doc_id sent_index relation_id relation trigger trigger_offset arg_num arg_head arg_protein arg_domain arg_site arg_sugar arg_head_offset arg_base_np arg_base_np_offset arg_np arg_np_offset sent_text 26458842 1 0 link N-linked 86:93 arg1 glycosylation 103:115 N-linked protein glycosylation 86:115 N-linked protein glycosylation 86:115 N-linked protein glycosylation is involved in various biological processes, such as protein quality control and adhesion or signaling among cells. 26458842 6 1 theme conserved 1004:1012 arg1 sites 1030:1034 the lost ancestrally conserved N-glycosylation sites 983:1034 the lost ancestrally conserved N-glycosylation sites identified in the present study 983:1066 Thus, the lost ancestrally conserved N-glycosylation sites identified in the present study may be useful targets for functional analyses to identify molecular changes linked with the evolution of human phenotypes. 26458842 6 1 theme conserved 1004:1012 arg1 targets 1082:1088 useful targets 1075:1088 useful targets for functional analyses 1075:1112 Thus, the lost ancestrally conserved N-glycosylation sites identified in the present study may be useful targets for functional analyses to identify molecular changes linked with the evolution of human phenotypes. 26458842 6 2 theme functional 1094:1103 arg1 analyses 1105:1112 functional analyses 1094:1112 functional analyses 1094:1112 Thus, the lost ancestrally conserved N-glycosylation sites identified in the present study may be useful targets for functional analyses to identify molecular changes linked with the evolution of human phenotypes. 26458842 3 3 theme present 359:365 arg1 study 367:371 the present study 355:371 the present study 355:371 In the present study, a mouse glycoproteome dataset and mammalian proteome data were assessed to identify 40 ancestral N-glycosylation sites in 37 proteins that disappeared during human evolution since the last common ancestor of the Euarchonta (primates and treeshrews). 26458842 0 4 from Loss 0:3 arg1 proteins 53:60 conserved proteins 43:60 conserved proteins 43:60 Loss of ancestral N-glycosylation sites in conserved proteins during human evolution. 26458842 3 5 theme glycoproteome 382:394 arg1 dataset 396:402 a mouse glycoproteome dataset 374:402 a mouse glycoproteome dataset 374:402 In the present study, a mouse glycoproteome dataset and mammalian proteome data were assessed to identify 40 ancestral N-glycosylation sites in 37 proteins that disappeared during human evolution since the last common ancestor of the Euarchonta (primates and treeshrews). 26458842 5 6 theme system 895:900 arg1 development 845:855 normal development 838:855 normal development 838:855 Notably, CELSR1 and ST3GAL5 are crucial for normal development and function of the mammalian nervous system, suggesting an association with the evolution of human cognitive function. 26458842 5 6 theme system 895:900 arg1 function 861:868 function 861:868 function 861:868 Notably, CELSR1 and ST3GAL5 are crucial for normal development and function of the mammalian nervous system, suggesting an association with the evolution of human cognitive function. 26458842 5 7 theme cognitive 957:965 arg1 function 967:974 human cognitive function 951:974 human cognitive function 951:974 Notably, CELSR1 and ST3GAL5 are crucial for normal development and function of the mammalian nervous system, suggesting an association with the evolution of human cognitive function. 26458842 6 8 theme lost 987:990 arg1 sites 1030:1034 the lost ancestrally conserved N-glycosylation sites 983:1034 the lost ancestrally conserved N-glycosylation sites identified in the present study 983:1066 Thus, the lost ancestrally conserved N-glycosylation sites identified in the present study may be useful targets for functional analyses to identify molecular changes linked with the evolution of human phenotypes. 26458842 6 8 theme lost 987:990 arg1 targets 1082:1088 useful targets 1075:1088 useful targets for functional analyses 1075:1112 Thus, the lost ancestrally conserved N-glycosylation sites identified in the present study may be useful targets for functional analyses to identify molecular changes linked with the evolution of human phenotypes. 26458842 1 9 theme N-linked 86:93 arg1 glycosylation 103:115 N-linked protein glycosylation 86:115 N-linked protein glycosylation 86:115 N-linked protein glycosylation is involved in various biological processes, such as protein quality control and adhesion or signaling among cells. 26458842 3 10 theme last 558:561 arg1 ancestor 570:577 the last common ancestor 554:577 the last common ancestor of the Euarchonta 554:595 In the present study, a mouse glycoproteome dataset and mammalian proteome data were assessed to identify 40 ancestral N-glycosylation sites in 37 proteins that disappeared during human evolution since the last common ancestor of the Euarchonta (primates and treeshrews). 26458842 6 11 theme molecular 1126:1134 arg1 changes 1136:1142 molecular changes 1126:1142 molecular changes linked with the evolution of human phenotypes 1126:1188 Thus, the lost ancestrally conserved N-glycosylation sites identified in the present study may be useful targets for functional analyses to identify molecular changes linked with the evolution of human phenotypes. 26458842 5 12 theme normal 838:843 arg1 development 845:855 normal development 838:855 normal development 838:855 Notably, CELSR1 and ST3GAL5 are crucial for normal development and function of the mammalian nervous system, suggesting an association with the evolution of human cognitive function. 26458842 1 13 theme protein 170:176 arg1 control 186:192 protein quality control 170:192 protein quality control 170:192 N-linked protein glycosylation is involved in various biological processes, such as protein quality control and adhesion or signaling among cells. 26458842 1 14 gly glycosylation 103:115 arg1 control 186:192 protein quality control 170:192 protein quality control 170:192 N-linked protein glycosylation is involved in various biological processes, such as protein quality control and adhesion or signaling among cells. 26458842 1 14 gly glycosylation 103:115 arg1 adhesion 198:205 adhesion 198:205 adhesion 198:205 N-linked protein glycosylation is involved in various biological processes, such as protein quality control and adhesion or signaling among cells. 26458842 1 14 gly glycosylation 103:115 arg1 processes 151:159 various biological processes 132:159 various biological processes 132:159 N-linked protein glycosylation is involved in various biological processes, such as protein quality control and adhesion or signaling among cells. 26458842 3 15 from sites 487:491 arg1 proteins 499:506 37 proteins 496:506 37 proteins that disappeared during human evolution since the last common ancestor of the Euarchonta (primates and treeshrews) 496:621 In the present study, a mouse glycoproteome dataset and mammalian proteome data were assessed to identify 40 ancestral N-glycosylation sites in 37 proteins that disappeared during human evolution since the last common ancestor of the Euarchonta (primates and treeshrews). 26458842 2 16 theme sites 283:287 arg1 loss 237:240 The loss 233:240 The loss of ancestrally conserved N-glycosylation sites 233:287 The loss of ancestrally conserved N-glycosylation sites may result in the evolution of protein structure and function. 26458842 1 17 theme quality 178:184 arg1 control 186:192 protein quality control 170:192 protein quality control 170:192 N-linked protein glycosylation is involved in various biological processes, such as protein quality control and adhesion or signaling among cells. 26458842 3 18 theme mouse 376:380 arg1 dataset 396:402 a mouse glycoproteome dataset 374:402 a mouse glycoproteome dataset 374:402 In the present study, a mouse glycoproteome dataset and mammalian proteome data were assessed to identify 40 ancestral N-glycosylation sites in 37 proteins that disappeared during human evolution since the last common ancestor of the Euarchonta (primates and treeshrews). 26458842 6 19 theme human 1173:1177 arg1 phenotypes 1179:1188 human phenotypes 1173:1188 human phenotypes 1173:1188 Thus, the lost ancestrally conserved N-glycosylation sites identified in the present study may be useful targets for functional analyses to identify molecular changes linked with the evolution of human phenotypes. 26458842 2 20 theme protein 320:326 arg1 evolution 307:315 the evolution 303:315 the evolution of protein structure and function 303:349 The loss of ancestrally conserved N-glycosylation sites may result in the evolution of protein structure and function. 26458842 6 21 theme useful 1075:1080 arg1 sites 1030:1034 the lost ancestrally conserved N-glycosylation sites 983:1034 the lost ancestrally conserved N-glycosylation sites identified in the present study 983:1066 Thus, the lost ancestrally conserved N-glycosylation sites identified in the present study may be useful targets for functional analyses to identify molecular changes linked with the evolution of human phenotypes. 26458842 6 21 theme useful 1075:1080 arg1 targets 1082:1088 useful targets 1075:1088 useful targets for functional analyses 1075:1112 Thus, the lost ancestrally conserved N-glycosylation sites identified in the present study may be useful targets for functional analyses to identify molecular changes linked with the evolution of human phenotypes. 26458842 2 22 gly N-glycosylation 267:281 arg2 sites 283:287 ancestrally conserved N-glycosylation sites 245:287 ancestrally conserved N-glycosylation sites 245:287 The loss of ancestrally conserved N-glycosylation sites may result in the evolution of protein structure and function. 26458842 5 23 with association 917:927 arg1 evolution 938:946 the evolution 934:946 the evolution of human cognitive function 934:974 Notably, CELSR1 and ST3GAL5 are crucial for normal development and function of the mammalian nervous system, suggesting an association with the evolution of human cognitive function. 26458842 1 24 theme protein 95:101 arg1 glycosylation 103:115 N-linked protein glycosylation 86:115 N-linked protein glycosylation 86:115 N-linked protein glycosylation is involved in various biological processes, such as protein quality control and adhesion or signaling among cells. 26458842 4 25 theme human 660:664 arg1 VSIG10 696:701 VSIG10 696:701 VSIG10 696:701 The results showed that each of the human proteins, CELSR1, ST3GAL5 and VSIG10, lost an ancestrally conserved N-glycosylation site following human-chimpanzee divergence. 26458842 4 25 theme human 660:664 arg1 ST3GAL5 684:690 ST3GAL5 684:690 ST3GAL5 684:690 The results showed that each of the human proteins, CELSR1, ST3GAL5 and VSIG10, lost an ancestrally conserved N-glycosylation site following human-chimpanzee divergence. 26458842 4 25 theme human 660:664 arg1 CELSR1 676:681 CELSR1 676:681 CELSR1 676:681 The results showed that each of the human proteins, CELSR1, ST3GAL5 and VSIG10, lost an ancestrally conserved N-glycosylation site following human-chimpanzee divergence. 26458842 4 25 theme human 660:664 arg1 proteins 666:673 the human proteins 656:673 the human proteins 656:673 The results showed that each of the human proteins, CELSR1, ST3GAL5 and VSIG10, lost an ancestrally conserved N-glycosylation site following human-chimpanzee divergence. 26458842 0 26 theme N-glycosylation 18:32 arg1 sites 34:38 ancestral N-glycosylation sites 8:38 ancestral N-glycosylation sites 8:38 Loss of ancestral N-glycosylation sites in conserved proteins during human evolution. 26458842 3 27 theme common 563:568 arg1 ancestor 570:577 the last common ancestor 554:577 the last common ancestor of the Euarchonta 554:595 In the present study, a mouse glycoproteome dataset and mammalian proteome data were assessed to identify 40 ancestral N-glycosylation sites in 37 proteins that disappeared during human evolution since the last common ancestor of the Euarchonta (primates and treeshrews). 26458842 3 28 theme ancestral 461:469 arg1 sites 487:491 40 ancestral N-glycosylation sites 458:491 40 ancestral N-glycosylation sites in 37 proteins that disappeared during human evolution since the last common ancestor of the Euarchonta (primates and treeshrews) 458:621 In the present study, a mouse glycoproteome dataset and mammalian proteome data were assessed to identify 40 ancestral N-glycosylation sites in 37 proteins that disappeared during human evolution since the last common ancestor of the Euarchonta (primates and treeshrews). 26458842 0 29 theme ancestral 8:16 arg1 sites 34:38 ancestral N-glycosylation sites 8:38 ancestral N-glycosylation sites 8:38 Loss of ancestral N-glycosylation sites in conserved proteins during human evolution. 26458842 5 30 theme human 951:955 arg1 function 967:974 human cognitive function 951:974 human cognitive function 951:974 Notably, CELSR1 and ST3GAL5 are crucial for normal development and function of the mammalian nervous system, suggesting an association with the evolution of human cognitive function. 26458842 4 31 theme conserved 724:732 arg1 site 750:753 an ancestrally conserved N-glycosylation site 709:753 an ancestrally conserved N-glycosylation site 709:753 The results showed that each of the human proteins, CELSR1, ST3GAL5 and VSIG10, lost an ancestrally conserved N-glycosylation site following human-chimpanzee divergence. 26458842 3 32 theme N-glycosylation 471:485 arg1 sites 487:491 40 ancestral N-glycosylation sites 458:491 40 ancestral N-glycosylation sites in 37 proteins that disappeared during human evolution since the last common ancestor of the Euarchonta (primates and treeshrews) 458:621 In the present study, a mouse glycoproteome dataset and mammalian proteome data were assessed to identify 40 ancestral N-glycosylation sites in 37 proteins that disappeared during human evolution since the last common ancestor of the Euarchonta (primates and treeshrews). 26458842 3 33 theme mammalian 408:416 arg1 data 427:430 a mouse glycoproteome dataset and mammalian proteome data 374:430 a mouse glycoproteome dataset and mammalian proteome data 374:430 In the present study, a mouse glycoproteome dataset and mammalian proteome data were assessed to identify 40 ancestral N-glycosylation sites in 37 proteins that disappeared during human evolution since the last common ancestor of the Euarchonta (primates and treeshrews). 26458842 5 34 theme function 967:974 arg1 evolution 938:946 the evolution 934:946 the evolution of human cognitive function 934:974 Notably, CELSR1 and ST3GAL5 are crucial for normal development and function of the mammalian nervous system, suggesting an association with the evolution of human cognitive function. 26458842 3 35 gly N-glycosylation 471:485 arg2 sites 487:491 40 ancestral N-glycosylation sites 458:491 40 ancestral N-glycosylation sites in 37 proteins that disappeared during human evolution since the last common ancestor of the Euarchonta (primates and treeshrews) 458:621 In the present study, a mouse glycoproteome dataset and mammalian proteome data were assessed to identify 40 ancestral N-glycosylation sites in 37 proteins that disappeared during human evolution since the last common ancestor of the Euarchonta (primates and treeshrews). 26458842 3 35 gly N-glycosylation 471:485 arg2 40 458:459 40 458:459 40 458:459 In the present study, a mouse glycoproteome dataset and mammalian proteome data were assessed to identify 40 ancestral N-glycosylation sites in 37 proteins that disappeared during human evolution since the last common ancestor of the Euarchonta (primates and treeshrews). 26458842 5 36 theme mammalian 877:885 arg1 system 895:900 the mammalian nervous system 873:900 the mammalian nervous system 873:900 Notably, CELSR1 and ST3GAL5 are crucial for normal development and function of the mammalian nervous system, suggesting an association with the evolution of human cognitive function. 26458842 6 37 theme present 1054:1060 arg1 study 1062:1066 the present study 1050:1066 the present study 1050:1066 Thus, the lost ancestrally conserved N-glycosylation sites identified in the present study may be useful targets for functional analyses to identify molecular changes linked with the evolution of human phenotypes. 26458842 0 38 theme sites 34:38 arg1 Loss 0:3 Loss 0:3 Loss of ancestral N-glycosylation sites in conserved proteins 0:60 Loss of ancestral N-glycosylation sites in conserved proteins during human evolution. 26458842 3 39 theme proteome 418:425 arg1 data 427:430 a mouse glycoproteome dataset and mammalian proteome data 374:430 a mouse glycoproteome dataset and mammalian proteome data 374:430 In the present study, a mouse glycoproteome dataset and mammalian proteome data were assessed to identify 40 ancestral N-glycosylation sites in 37 proteins that disappeared during human evolution since the last common ancestor of the Euarchonta (primates and treeshrews). 26458842 4 40 gly N-glycosylation 734:748 arg2 site 750:753 an ancestrally conserved N-glycosylation site 709:753 an ancestrally conserved N-glycosylation site 709:753 The results showed that each of the human proteins, CELSR1, ST3GAL5 and VSIG10, lost an ancestrally conserved N-glycosylation site following human-chimpanzee divergence. 26458842 3 41 theme dataset 396:402 arg1 data 427:430 a mouse glycoproteome dataset and mammalian proteome data 374:430 a mouse glycoproteome dataset and mammalian proteome data 374:430 In the present study, a mouse glycoproteome dataset and mammalian proteome data were assessed to identify 40 ancestral N-glycosylation sites in 37 proteins that disappeared during human evolution since the last common ancestor of the Euarchonta (primates and treeshrews). 26458842 3 42 theme Euarchonta 586:595 arg1 ancestor 570:577 the last common ancestor 554:577 the last common ancestor of the Euarchonta 554:595 In the present study, a mouse glycoproteome dataset and mammalian proteome data were assessed to identify 40 ancestral N-glycosylation sites in 37 proteins that disappeared during human evolution since the last common ancestor of the Euarchonta (primates and treeshrews). 26458842 0 43 theme conserved 43:51 arg1 proteins 53:60 conserved proteins 43:60 conserved proteins 43:60 Loss of ancestral N-glycosylation sites in conserved proteins during human evolution. 26458842 0 44 gly N-glycosylation 18:32 arg2 sites 34:38 ancestral N-glycosylation sites 8:38 ancestral N-glycosylation sites 8:38 Loss of ancestral N-glycosylation sites in conserved proteins during human evolution. 26458842 3 45 dep disappeared 513:523 arg1 primates 598:605 primates 598:605 primates 598:605 In the present study, a mouse glycoproteome dataset and mammalian proteome data were assessed to identify 40 ancestral N-glycosylation sites in 37 proteins that disappeared during human evolution since the last common ancestor of the Euarchonta (primates and treeshrews). 26458842 3 45 dep disappeared 513:523 arg1 treeshrews 611:620 treeshrews 611:620 treeshrews 611:620 In the present study, a mouse glycoproteome dataset and mammalian proteome data were assessed to identify 40 ancestral N-glycosylation sites in 37 proteins that disappeared during human evolution since the last common ancestor of the Euarchonta (primates and treeshrews). 26458842 2 46 theme N-glycosylation 267:281 arg1 sites 283:287 ancestrally conserved N-glycosylation sites 245:287 ancestrally conserved N-glycosylation sites 245:287 The loss of ancestrally conserved N-glycosylation sites may result in the evolution of protein structure and function. 26458842 1 47 theme various 132:138 arg1 control 186:192 protein quality control 170:192 protein quality control 170:192 N-linked protein glycosylation is involved in various biological processes, such as protein quality control and adhesion or signaling among cells. 26458842 1 47 theme various 132:138 arg1 adhesion 198:205 adhesion 198:205 adhesion 198:205 N-linked protein glycosylation is involved in various biological processes, such as protein quality control and adhesion or signaling among cells. 26458842 1 47 theme various 132:138 arg1 processes 151:159 various biological processes 132:159 various biological processes 132:159 N-linked protein glycosylation is involved in various biological processes, such as protein quality control and adhesion or signaling among cells. 26458842 4 48 theme N-glycosylation 734:748 arg1 site 750:753 an ancestrally conserved N-glycosylation site 709:753 an ancestrally conserved N-glycosylation site 709:753 The results showed that each of the human proteins, CELSR1, ST3GAL5 and VSIG10, lost an ancestrally conserved N-glycosylation site following human-chimpanzee divergence. 26458842 4 49 theme human-chimpanzee 765:780 arg1 divergence 782:791 human-chimpanzee divergence 765:791 human-chimpanzee divergence 765:791 The results showed that each of the human proteins, CELSR1, ST3GAL5 and VSIG10, lost an ancestrally conserved N-glycosylation site following human-chimpanzee divergence. 26458842 2 50 theme conserved 257:265 arg1 sites 283:287 ancestrally conserved N-glycosylation sites 245:287 ancestrally conserved N-glycosylation sites 245:287 The loss of ancestrally conserved N-glycosylation sites may result in the evolution of protein structure and function. 26458842 1 51 theme biological 140:149 arg1 control 186:192 protein quality control 170:192 protein quality control 170:192 N-linked protein glycosylation is involved in various biological processes, such as protein quality control and adhesion or signaling among cells. 26458842 1 51 theme biological 140:149 arg1 adhesion 198:205 adhesion 198:205 adhesion 198:205 N-linked protein glycosylation is involved in various biological processes, such as protein quality control and adhesion or signaling among cells. 26458842 1 51 theme biological 140:149 arg1 processes 151:159 various biological processes 132:159 various biological processes 132:159 N-linked protein glycosylation is involved in various biological processes, such as protein quality control and adhesion or signaling among cells. 26458842 2 52 dep protein 320:326 arg1 function 342:349 function 342:349 function 342:349 The loss of ancestrally conserved N-glycosylation sites may result in the evolution of protein structure and function. 26458842 2 52 dep protein 320:326 arg1 structure 328:336 structure 328:336 structure 328:336 The loss of ancestrally conserved N-glycosylation sites may result in the evolution of protein structure and function. 26458842 0 53 theme human 69:73 arg1 evolution 75:83 human evolution 69:83 human evolution 69:83 Loss of ancestral N-glycosylation sites in conserved proteins during human evolution. 26458842 6 54 theme phenotypes 1179:1188 arg1 evolution 1160:1168 the evolution 1156:1168 the evolution of human phenotypes 1156:1188 Thus, the lost ancestrally conserved N-glycosylation sites identified in the present study may be useful targets for functional analyses to identify molecular changes linked with the evolution of human phenotypes. 26458842 5 55 theme nervous 887:893 arg1 system 895:900 the mammalian nervous system 873:900 the mammalian nervous system 873:900 Notably, CELSR1 and ST3GAL5 are crucial for normal development and function of the mammalian nervous system, suggesting an association with the evolution of human cognitive function. 26458842 0 56 dep Loss 0:3 arg1 evolution 75:83 human evolution 69:83 human evolution 69:83 Loss of ancestral N-glycosylation sites in conserved proteins during human evolution. 26458842 6 57 gly N-glycosylation 1014:1028 arg2 sites 1030:1034 the lost ancestrally conserved N-glycosylation sites 983:1034 the lost ancestrally conserved N-glycosylation sites identified in the present study 983:1066 Thus, the lost ancestrally conserved N-glycosylation sites identified in the present study may be useful targets for functional analyses to identify molecular changes linked with the evolution of human phenotypes. 26458842 6 57 gly N-glycosylation 1014:1028 arg2 targets 1082:1088 useful targets 1075:1088 useful targets for functional analyses 1075:1112 Thus, the lost ancestrally conserved N-glycosylation sites identified in the present study may be useful targets for functional analyses to identify molecular changes linked with the evolution of human phenotypes. 26458842 3 58 theme human 532:536 arg1 evolution 538:546 human evolution 532:546 human evolution 532:546 In the present study, a mouse glycoproteome dataset and mammalian proteome data were assessed to identify 40 ancestral N-glycosylation sites in 37 proteins that disappeared during human evolution since the last common ancestor of the Euarchonta (primates and treeshrews). 26458842 6 59 theme N-glycosylation 1014:1028 arg1 sites 1030:1034 the lost ancestrally conserved N-glycosylation sites 983:1034 the lost ancestrally conserved N-glycosylation sites identified in the present study 983:1066 Thus, the lost ancestrally conserved N-glycosylation sites identified in the present study may be useful targets for functional analyses to identify molecular changes linked with the evolution of human phenotypes. 26458842 6 59 theme N-glycosylation 1014:1028 arg1 targets 1082:1088 useful targets 1075:1088 useful targets for functional analyses 1075:1112 Thus, the lost ancestrally conserved N-glycosylation sites identified in the present study may be useful targets for functional analyses to identify molecular changes linked with the evolution of human phenotypes. 24361341 10 0 theme further 1714:1720 arg1 study 1722:1726 further study 1714:1726 further study 1714:1726 As is true for NOX2, the contribution of glycosylation in NOX1 to its biologic function(s) merits further study. 24361341 9 1 theme specific 1444:1451 arg1 sites 1453:1457 the two specific sites 1436:1457 the two specific sites of N-linked glycosylation of murine NOX1 1436:1498 Taken together, these data identify the two specific sites of N-linked glycosylation of murine NOX1 and demonstrate that they are not required for normal enzyme activity, protein stability, and membrane trafficking. 24361341 9 1 theme specific 1444:1451 arg1 glycosylation 1471:1483 N-linked glycosylation 1462:1483 N-linked glycosylation of murine NOX1 1462:1498 Taken together, these data identify the two specific sites of N-linked glycosylation of murine NOX1 and demonstrate that they are not required for normal enzyme activity, protein stability, and membrane trafficking. 24361341 8 2 from Elimination 1203:1213 arg1 NOX1 1237:1240 NOX1 1237:1240 NOX1 1237:1240 Elimination of N-glycosylation on NOX1 did not affect its electron transferase activity, protein stability, targeting to the cell surface, or localization in F-actin-positive membrane protrusions. 24361341 5 3 dep identified 820:829 arg1 whereas 876:882 whereas 876:882 whereas 876:882 Based on differential sensitivity to glycosidases, the doublet was identified as two high-mannose-type glycoforms of NOX1, whereas the broad band represented NOX1 with complex-type N-linked oligosaccharides. 24361341 5 4 theme N-linked 934:941 arg1 oligosaccharides 943:958 complex-type N-linked oligosaccharides 921:958 complex-type N-linked oligosaccharides 921:958 Based on differential sensitivity to glycosidases, the doublet was identified as two high-mannose-type glycoforms of NOX1, whereas the broad band represented NOX1 with complex-type N-linked oligosaccharides. 24361341 8 5 theme electron 1261:1268 arg1 activity 1282:1289 its electron transferase activity 1257:1289 its electron transferase activity 1257:1289 Elimination of N-glycosylation on NOX1 did not affect its electron transferase activity, protein stability, targeting to the cell surface, or localization in F-actin-positive membrane protrusions. 24361341 1 6 theme superoxide-generating 193:213 arg1 oxidase 228:234 superoxide-generating enzyme NADPH oxidase 193:234 superoxide-generating enzyme NADPH oxidase 193:234 Extensive evidence demonstrates the pathophysiological importance of NOX1, the catalytic subunit of superoxide-generating enzyme NADPH oxidase, as a source of reactive oxygen species in nonphagocytic cells. 24361341 4 7 theme 56 699:700 arg1 doublet 688:694 a doublet 686:694 a doublet of 56 and 60kDa accompanied by a broad band of 60-90kDa 686:750 Immunoblots of lysates from cells expressing NOX1 revealed a doublet of 56 and 60kDa accompanied by a broad band of 60-90kDa. 24361341 9 8 theme murine 1488:1493 arg1 NOX1 1495:1498 murine NOX1 1488:1498 murine NOX1 1488:1498 Taken together, these data identify the two specific sites of N-linked glycosylation of murine NOX1 and demonstrate that they are not required for normal enzyme activity, protein stability, and membrane trafficking. 24361341 8 9 theme protein 1292:1298 arg1 stability 1300:1308 protein stability 1292:1308 protein stability 1292:1308 Elimination of N-glycosylation on NOX1 did not affect its electron transferase activity, protein stability, targeting to the cell surface, or localization in F-actin-positive membrane protrusions. 24361341 1 10 from cells 293:297 arg1 source 242:247 a source 240:247 a source of reactive oxygen species in nonphagocytic cells 240:297 Extensive evidence demonstrates the pathophysiological importance of NOX1, the catalytic subunit of superoxide-generating enzyme NADPH oxidase, as a source of reactive oxygen species in nonphagocytic cells. 24361341 1 10 from cells 293:297 arg1 importance 148:157 the pathophysiological importance 125:157 the pathophysiological importance of NOX1, the catalytic subunit of superoxide-generating enzyme NADPH oxidase, 125:235 Extensive evidence demonstrates the pathophysiological importance of NOX1, the catalytic subunit of superoxide-generating enzyme NADPH oxidase, as a source of reactive oxygen species in nonphagocytic cells. 24361341 2 11 theme biochemical 313:323 arg1 properties 325:334 the biochemical properties 309:334 the biochemical properties of NOX1 309:342 However, the biochemical properties of NOX1 have not been extensively characterized due to a lack of specific immunological tools. 24361341 8 12 from activity 1282:1289 arg1 protrusions 1387:1397 F-actin-positive membrane protrusions 1361:1397 F-actin-positive membrane protrusions 1361:1397 Elimination of N-glycosylation on NOX1 did not affect its electron transferase activity, protein stability, targeting to the cell surface, or localization in F-actin-positive membrane protrusions. 24361341 4 13 theme broad 729:733 arg1 band 735:738 a broad band 727:738 a broad band of 60-90kDa 727:750 Immunoblots of lysates from cells expressing NOX1 revealed a doublet of 56 and 60kDa accompanied by a broad band of 60-90kDa. 24361341 8 14 theme cell 1328:1331 arg1 surface 1333:1339 the cell surface 1324:1339 the cell surface 1324:1339 Elimination of N-glycosylation on NOX1 did not affect its electron transferase activity, protein stability, targeting to the cell surface, or localization in F-actin-positive membrane protrusions. 24361341 7 15 theme Site-directed 1078:1090 arg1 mutagenesis 1092:1102 Site-directed mutagenesis 1078:1102 Site-directed mutagenesis 1078:1102 Site-directed mutagenesis identified N-glycosylation sites at Asn(161) and Asn(241) on the extracellular loop of mouse NOX1. 24361341 1 16 theme NOX1 162:165 arg1 source 242:247 a source 240:247 a source of reactive oxygen species in nonphagocytic cells 240:297 Extensive evidence demonstrates the pathophysiological importance of NOX1, the catalytic subunit of superoxide-generating enzyme NADPH oxidase, as a source of reactive oxygen species in nonphagocytic cells. 24361341 1 16 theme NOX1 162:165 arg1 importance 148:157 the pathophysiological importance 125:157 the pathophysiological importance of NOX1, the catalytic subunit of superoxide-generating enzyme NADPH oxidase, 125:235 Extensive evidence demonstrates the pathophysiological importance of NOX1, the catalytic subunit of superoxide-generating enzyme NADPH oxidase, as a source of reactive oxygen species in nonphagocytic cells. 24361341 4 17 theme 60kDa 706:710 arg1 doublet 688:694 a doublet 686:694 a doublet of 56 and 60kDa accompanied by a broad band of 60-90kDa 686:750 Immunoblots of lysates from cells expressing NOX1 revealed a doublet of 56 and 60kDa accompanied by a broad band of 60-90kDa. 24361341 5 18 theme high-mannose-type 838:854 arg1 doublet 808:814 the doublet 804:814 the doublet 804:814 Based on differential sensitivity to glycosidases, the doublet was identified as two high-mannose-type glycoforms of NOX1, whereas the broad band represented NOX1 with complex-type N-linked oligosaccharides. 24361341 5 18 theme high-mannose-type 838:854 arg1 glycoforms 856:865 two high-mannose-type glycoforms 834:865 two high-mannose-type glycoforms of NOX1 834:873 Based on differential sensitivity to glycosidases, the doublet was identified as two high-mannose-type glycoforms of NOX1, whereas the broad band represented NOX1 with complex-type N-linked oligosaccharides. 24361341 9 19 theme normal 1547:1552 arg1 activity 1561:1568 normal enzyme activity 1547:1568 normal enzyme activity 1547:1568 Taken together, these data identify the two specific sites of N-linked glycosylation of murine NOX1 and demonstrate that they are not required for normal enzyme activity, protein stability, and membrane trafficking. 24361341 6 20 gly Deglycosylated 961:974 arg1 NOX1 976:979 Deglycosylated NOX1 961:979 Deglycosylated NOX1 migrated at ~53kDa and N-glycosylation 961:1018 Deglycosylated NOX1 migrated at ~53kDa and N-glycosylation was demonstrated in NOX1 derived from both rat and human. 24361341 0 21 theme oxidase 84:90 arg1 oxidase 84:90 NOX1/NADPH oxidase 73:90 NOX1/NADPH oxidase 73:90 Characterization of N-glycosylation sites on the extracellular domain of NOX1/NADPH oxidase. 24361341 0 21 theme oxidase 84:90 arg1 domain 63:68 the extracellular domain 45:68 the extracellular domain of NOX1/NADPH oxidase 45:90 Characterization of N-glycosylation sites on the extracellular domain of NOX1/NADPH oxidase. 24361341 5 22 theme complex-type 921:932 arg1 oligosaccharides 943:958 complex-type N-linked oligosaccharides 921:958 complex-type N-linked oligosaccharides 921:958 Based on differential sensitivity to glycosidases, the doublet was identified as two high-mannose-type glycoforms of NOX1, whereas the broad band represented NOX1 with complex-type N-linked oligosaccharides. 24361341 0 23 from Characterization 0:15 arg1 oxidase 84:90 NOX1/NADPH oxidase 73:90 NOX1/NADPH oxidase 73:90 Characterization of N-glycosylation sites on the extracellular domain of NOX1/NADPH oxidase. 24361341 0 23 from Characterization 0:15 arg1 domain 63:68 the extracellular domain 45:68 the extracellular domain of NOX1/NADPH oxidase 45:90 Characterization of N-glycosylation sites on the extracellular domain of NOX1/NADPH oxidase. 24361341 8 24 theme F-actin-positive 1361:1376 arg1 protrusions 1387:1397 F-actin-positive membrane protrusions 1361:1397 F-actin-positive membrane protrusions 1361:1397 Elimination of N-glycosylation on NOX1 did not affect its electron transferase activity, protein stability, targeting to the cell surface, or localization in F-actin-positive membrane protrusions. 24361341 9 25 theme protein 1571:1577 arg1 stability 1579:1587 protein stability 1571:1587 protein stability 1571:1587 Taken together, these data identify the two specific sites of N-linked glycosylation of murine NOX1 and demonstrate that they are not required for normal enzyme activity, protein stability, and membrane trafficking. 24361341 2 26 theme immunological 410:422 arg1 tools 424:428 specific immunological tools 401:428 specific immunological tools 401:428 However, the biochemical properties of NOX1 have not been extensively characterized due to a lack of specific immunological tools. 24361341 8 27 from localization 1345:1356 arg1 protrusions 1387:1397 F-actin-positive membrane protrusions 1361:1397 F-actin-positive membrane protrusions 1361:1397 Elimination of N-glycosylation on NOX1 did not affect its electron transferase activity, protein stability, targeting to the cell surface, or localization in F-actin-positive membrane protrusions. 24361341 0 28 theme NOX1/NADPH 73:82 arg1 oxidase 84:90 NOX1/NADPH oxidase 73:90 NOX1/NADPH oxidase 73:90 Characterization of N-glycosylation sites on the extracellular domain of NOX1/NADPH oxidase. 24361341 10 29 theme glycosylation 1657:1669 arg1 contribution 1641:1652 the contribution 1637:1652 the contribution of glycosylation in NOX1 to its biologic function(s) 1637:1705 As is true for NOX2, the contribution of glycosylation in NOX1 to its biologic function(s) merits further study. 24361341 9 30 theme membrane 1594:1601 arg1 trafficking 1603:1613 membrane trafficking 1594:1613 membrane trafficking 1594:1613 Taken together, these data identify the two specific sites of N-linked glycosylation of murine NOX1 and demonstrate that they are not required for normal enzyme activity, protein stability, and membrane trafficking. 24361341 10 31 theme function 1695:1702 arg1 s 1704:1704 its biologic function(s) 1682:1705 its biologic function(s) 1682:1705 As is true for NOX2, the contribution of glycosylation in NOX1 to its biologic function(s) merits further study. 24361341 0 32 theme N-glycosylation 20:34 arg1 sites 36:40 N-glycosylation sites 20:40 N-glycosylation sites 20:40 Characterization of N-glycosylation sites on the extracellular domain of NOX1/NADPH oxidase. 24361341 3 33 theme polyclonal 459:468 arg1 antibody 470:477 a newly raised NOX1 polyclonal antibody 439:477 a newly raised NOX1 polyclonal antibody 439:477 We used a newly raised NOX1 polyclonal antibody to investigate posttranslational modifications of NOX1 overexpressed in cultured cells and in the colon, where endogenous NOX1 is highly expressed. 24361341 0 34 theme extracellular 49:61 arg1 oxidase 84:90 NOX1/NADPH oxidase 73:90 NOX1/NADPH oxidase 73:90 Characterization of N-glycosylation sites on the extracellular domain of NOX1/NADPH oxidase. 24361341 0 34 theme extracellular 49:61 arg1 domain 63:68 the extracellular domain 45:68 the extracellular domain of NOX1/NADPH oxidase 45:90 Characterization of N-glycosylation sites on the extracellular domain of NOX1/NADPH oxidase. 24361341 3 35 theme posttranslational 494:510 arg1 modifications 512:524 posttranslational modifications 494:524 posttranslational modifications of NOX1 overexpressed in cultured cells and in the colon, where endogenous NOX1 is highly expressed 494:624 We used a newly raised NOX1 polyclonal antibody to investigate posttranslational modifications of NOX1 overexpressed in cultured cells and in the colon, where endogenous NOX1 is highly expressed. 24361341 3 36 theme cultured 551:558 arg1 cells 560:564 cultured cells 551:564 cultured cells 551:564 We used a newly raised NOX1 polyclonal antibody to investigate posttranslational modifications of NOX1 overexpressed in cultured cells and in the colon, where endogenous NOX1 is highly expressed. 24361341 9 37 theme glycosylation 1471:1483 arg1 sites 1453:1457 the two specific sites 1436:1457 the two specific sites of N-linked glycosylation of murine NOX1 1436:1498 Taken together, these data identify the two specific sites of N-linked glycosylation of murine NOX1 and demonstrate that they are not required for normal enzyme activity, protein stability, and membrane trafficking. 24361341 9 37 theme glycosylation 1471:1483 arg1 glycosylation 1471:1483 N-linked glycosylation 1462:1483 N-linked glycosylation of murine NOX1 1462:1498 Taken together, these data identify the two specific sites of N-linked glycosylation of murine NOX1 and demonstrate that they are not required for normal enzyme activity, protein stability, and membrane trafficking. 24361341 1 38 theme reactive 252:259 arg1 species 268:274 reactive oxygen species 252:274 reactive oxygen species in nonphagocytic cells 252:297 Extensive evidence demonstrates the pathophysiological importance of NOX1, the catalytic subunit of superoxide-generating enzyme NADPH oxidase, as a source of reactive oxygen species in nonphagocytic cells. 24361341 6 39 theme Deglycosylated 961:974 arg1 NOX1 976:979 Deglycosylated NOX1 961:979 Deglycosylated NOX1 migrated at ~53kDa and N-glycosylation 961:1018 Deglycosylated NOX1 migrated at ~53kDa and N-glycosylation was demonstrated in NOX1 derived from both rat and human. 24361341 4 40 theme lysates 642:648 arg1 Immunoblots 627:637 Immunoblots 627:637 Immunoblots of lysates from cells expressing NOX1 627:675 Immunoblots of lysates from cells expressing NOX1 revealed a doublet of 56 and 60kDa accompanied by a broad band of 60-90kDa. 24361341 1 41 theme species 268:274 arg1 source 242:247 a source 240:247 a source of reactive oxygen species in nonphagocytic cells 240:297 Extensive evidence demonstrates the pathophysiological importance of NOX1, the catalytic subunit of superoxide-generating enzyme NADPH oxidase, as a source of reactive oxygen species in nonphagocytic cells. 24361341 1 41 theme species 268:274 arg1 importance 148:157 the pathophysiological importance 125:157 the pathophysiological importance of NOX1, the catalytic subunit of superoxide-generating enzyme NADPH oxidase, 125:235 Extensive evidence demonstrates the pathophysiological importance of NOX1, the catalytic subunit of superoxide-generating enzyme NADPH oxidase, as a source of reactive oxygen species in nonphagocytic cells. 24361341 6 42 attach derived 1045:1051 arg1 rat 1063:1065 rat 1063:1065 rat 1063:1065 Deglycosylated NOX1 migrated at ~53kDa and N-glycosylation was demonstrated in NOX1 derived from both rat and human. 24361341 6 42 attach derived 1045:1051 arg2 NOX1 1040:1043 NOX1 1040:1043 NOX1 derived from both rat and human 1040:1075 Deglycosylated NOX1 migrated at ~53kDa and N-glycosylation was demonstrated in NOX1 derived from both rat and human. 24361341 6 42 attach derived 1045:1051 arg1 human 1071:1075 human 1071:1075 human 1071:1075 Deglycosylated NOX1 migrated at ~53kDa and N-glycosylation was demonstrated in NOX1 derived from both rat and human. 24361341 1 43 theme nonphagocytic 279:291 arg1 cells 293:297 nonphagocytic cells 279:297 nonphagocytic cells 279:297 Extensive evidence demonstrates the pathophysiological importance of NOX1, the catalytic subunit of superoxide-generating enzyme NADPH oxidase, as a source of reactive oxygen species in nonphagocytic cells. 24361341 3 44 theme endogenous 590:599 arg1 NOX1 601:604 endogenous NOX1 590:604 endogenous NOX1 590:604 We used a newly raised NOX1 polyclonal antibody to investigate posttranslational modifications of NOX1 overexpressed in cultured cells and in the colon, where endogenous NOX1 is highly expressed. 24361341 9 45 theme enzyme 1554:1559 arg1 activity 1561:1568 normal enzyme activity 1547:1568 normal enzyme activity 1547:1568 Taken together, these data identify the two specific sites of N-linked glycosylation of murine NOX1 and demonstrate that they are not required for normal enzyme activity, protein stability, and membrane trafficking. 24361341 5 46 theme broad 888:892 arg1 band 894:897 the broad band 884:897 the broad band 884:897 Based on differential sensitivity to glycosidases, the doublet was identified as two high-mannose-type glycoforms of NOX1, whereas the broad band represented NOX1 with complex-type N-linked oligosaccharides. 24361341 9 47 theme N-linked 1462:1469 arg1 glycosylation 1471:1483 N-linked glycosylation 1462:1483 N-linked glycosylation of murine NOX1 1462:1498 Taken together, these data identify the two specific sites of N-linked glycosylation of murine NOX1 and demonstrate that they are not required for normal enzyme activity, protein stability, and membrane trafficking. 24361341 10 48 from contribution 1641:1652 arg1 NOX1 1674:1677 NOX1 1674:1677 NOX1 1674:1677 As is true for NOX2, the contribution of glycosylation in NOX1 to its biologic function(s) merits further study. 24361341 5 49 gly glycoforms 856:865 arg1 NOX1 870:873 NOX1 870:873 NOX1 870:873 Based on differential sensitivity to glycosidases, the doublet was identified as two high-mannose-type glycoforms of NOX1, whereas the broad band represented NOX1 with complex-type N-linked oligosaccharides. 24361341 4 50 from Immunoblots 627:637 arg1 cells 655:659 cells 655:659 cells expressing NOX1 655:675 Immunoblots of lysates from cells expressing NOX1 revealed a doublet of 56 and 60kDa accompanied by a broad band of 60-90kDa. 24361341 2 51 theme NOX1 339:342 arg1 properties 325:334 the biochemical properties 309:334 the biochemical properties of NOX1 309:342 However, the biochemical properties of NOX1 have not been extensively characterized due to a lack of specific immunological tools. 24361341 1 52 theme enzyme 215:220 arg1 oxidase 228:234 superoxide-generating enzyme NADPH oxidase 193:234 superoxide-generating enzyme NADPH oxidase 193:234 Extensive evidence demonstrates the pathophysiological importance of NOX1, the catalytic subunit of superoxide-generating enzyme NADPH oxidase, as a source of reactive oxygen species in nonphagocytic cells. 24361341 8 53 theme transferase 1270:1280 arg1 activity 1282:1289 its electron transferase activity 1257:1289 its electron transferase activity 1257:1289 Elimination of N-glycosylation on NOX1 did not affect its electron transferase activity, protein stability, targeting to the cell surface, or localization in F-actin-positive membrane protrusions. 24361341 9 54 theme NOX1 1495:1498 arg1 glycosylation 1471:1483 N-linked glycosylation 1462:1483 N-linked glycosylation of murine NOX1 1462:1498 Taken together, these data identify the two specific sites of N-linked glycosylation of murine NOX1 and demonstrate that they are not required for normal enzyme activity, protein stability, and membrane trafficking. 24361341 8 55 theme N-glycosylation 1218:1232 arg1 Elimination 1203:1213 Elimination 1203:1213 Elimination of N-glycosylation on NOX1 1203:1240 Elimination of N-glycosylation on NOX1 did not affect its electron transferase activity, protein stability, targeting to the cell surface, or localization in F-actin-positive membrane protrusions. 24361341 9 56 gly glycosylation 1471:1483 arg2 sites 1453:1457 the two specific sites 1436:1457 the two specific sites of N-linked glycosylation of murine NOX1 1436:1498 Taken together, these data identify the two specific sites of N-linked glycosylation of murine NOX1 and demonstrate that they are not required for normal enzyme activity, protein stability, and membrane trafficking. 24361341 9 56 gly glycosylation 1471:1483 arg2 glycosylation 1471:1483 N-linked glycosylation 1462:1483 N-linked glycosylation of murine NOX1 1462:1498 Taken together, these data identify the two specific sites of N-linked glycosylation of murine NOX1 and demonstrate that they are not required for normal enzyme activity, protein stability, and membrane trafficking. 24361341 9 56 gly glycosylation 1471:1483 arg1 NOX1 1495:1498 murine NOX1 1488:1498 murine NOX1 1488:1498 Taken together, these data identify the two specific sites of N-linked glycosylation of murine NOX1 and demonstrate that they are not required for normal enzyme activity, protein stability, and membrane trafficking. 24361341 7 57 theme N-glycosylation 1115:1129 arg1 sites 1131:1135 N-glycosylation sites 1115:1135 N-glycosylation sites 1115:1135 Site-directed mutagenesis identified N-glycosylation sites at Asn(161) and Asn(241) on the extracellular loop of mouse NOX1. 24361341 1 58 theme NADPH 222:226 arg1 oxidase 228:234 superoxide-generating enzyme NADPH oxidase 193:234 superoxide-generating enzyme NADPH oxidase 193:234 Extensive evidence demonstrates the pathophysiological importance of NOX1, the catalytic subunit of superoxide-generating enzyme NADPH oxidase, as a source of reactive oxygen species in nonphagocytic cells. 24361341 5 59 theme NOX1 870:873 arg1 doublet 808:814 the doublet 804:814 the doublet 804:814 Based on differential sensitivity to glycosidases, the doublet was identified as two high-mannose-type glycoforms of NOX1, whereas the broad band represented NOX1 with complex-type N-linked oligosaccharides. 24361341 5 59 theme NOX1 870:873 arg1 glycoforms 856:865 two high-mannose-type glycoforms 834:865 two high-mannose-type glycoforms of NOX1 834:873 Based on differential sensitivity to glycosidases, the doublet was identified as two high-mannose-type glycoforms of NOX1, whereas the broad band represented NOX1 with complex-type N-linked oligosaccharides. 24361341 5 60 link N-linked 934:941 arg1 oligosaccharides 943:958 complex-type N-linked oligosaccharides 921:958 complex-type N-linked oligosaccharides 921:958 Based on differential sensitivity to glycosidases, the doublet was identified as two high-mannose-type glycoforms of NOX1, whereas the broad band represented NOX1 with complex-type N-linked oligosaccharides. 24361341 1 61 theme pathophysiological 129:146 arg1 source 242:247 a source 240:247 a source of reactive oxygen species in nonphagocytic cells 240:297 Extensive evidence demonstrates the pathophysiological importance of NOX1, the catalytic subunit of superoxide-generating enzyme NADPH oxidase, as a source of reactive oxygen species in nonphagocytic cells. 24361341 1 61 theme pathophysiological 129:146 arg1 importance 148:157 the pathophysiological importance 125:157 the pathophysiological importance of NOX1, the catalytic subunit of superoxide-generating enzyme NADPH oxidase, 125:235 Extensive evidence demonstrates the pathophysiological importance of NOX1, the catalytic subunit of superoxide-generating enzyme NADPH oxidase, as a source of reactive oxygen species in nonphagocytic cells. 24361341 1 62 from source 242:247 arg1 cells 293:297 nonphagocytic cells 279:297 nonphagocytic cells 279:297 Extensive evidence demonstrates the pathophysiological importance of NOX1, the catalytic subunit of superoxide-generating enzyme NADPH oxidase, as a source of reactive oxygen species in nonphagocytic cells. 24361341 5 63 theme differential 762:773 arg1 sensitivity 775:785 differential sensitivity 762:785 differential sensitivity to glycosidases 762:801 Based on differential sensitivity to glycosidases, the doublet was identified as two high-mannose-type glycoforms of NOX1, whereas the broad band represented NOX1 with complex-type N-linked oligosaccharides. 24361341 1 64 theme oxidase 228:234 arg1 NOX1 162:165 NOX1 162:165 NOX1 162:165 Extensive evidence demonstrates the pathophysiological importance of NOX1, the catalytic subunit of superoxide-generating enzyme NADPH oxidase, as a source of reactive oxygen species in nonphagocytic cells. 24361341 1 64 theme oxidase 228:234 arg1 subunit 182:188 the catalytic subunit 168:188 the catalytic subunit of superoxide-generating enzyme NADPH oxidase 168:234 Extensive evidence demonstrates the pathophysiological importance of NOX1, the catalytic subunit of superoxide-generating enzyme NADPH oxidase, as a source of reactive oxygen species in nonphagocytic cells. 24361341 1 65 theme catalytic 172:180 arg1 NOX1 162:165 NOX1 162:165 NOX1 162:165 Extensive evidence demonstrates the pathophysiological importance of NOX1, the catalytic subunit of superoxide-generating enzyme NADPH oxidase, as a source of reactive oxygen species in nonphagocytic cells. 24361341 1 65 theme catalytic 172:180 arg1 subunit 182:188 the catalytic subunit 168:188 the catalytic subunit of superoxide-generating enzyme NADPH oxidase 168:234 Extensive evidence demonstrates the pathophysiological importance of NOX1, the catalytic subunit of superoxide-generating enzyme NADPH oxidase, as a source of reactive oxygen species in nonphagocytic cells. 24361341 7 66 gly N-glycosylation 1115:1129 arg2 sites 1131:1135 N-glycosylation sites 1115:1135 N-glycosylation sites 1115:1135 Site-directed mutagenesis identified N-glycosylation sites at Asn(161) and Asn(241) on the extracellular loop of mouse NOX1. 24361341 8 67 from targeting 1311:1319 arg1 protrusions 1387:1397 F-actin-positive membrane protrusions 1361:1397 F-actin-positive membrane protrusions 1361:1397 Elimination of N-glycosylation on NOX1 did not affect its electron transferase activity, protein stability, targeting to the cell surface, or localization in F-actin-positive membrane protrusions. 24361341 8 68 theme membrane 1378:1385 arg1 protrusions 1387:1397 F-actin-positive membrane protrusions 1361:1397 F-actin-positive membrane protrusions 1361:1397 Elimination of N-glycosylation on NOX1 did not affect its electron transferase activity, protein stability, targeting to the cell surface, or localization in F-actin-positive membrane protrusions. 24361341 3 69 theme NOX1 454:457 arg1 antibody 470:477 a newly raised NOX1 polyclonal antibody 439:477 a newly raised NOX1 polyclonal antibody 439:477 We used a newly raised NOX1 polyclonal antibody to investigate posttranslational modifications of NOX1 overexpressed in cultured cells and in the colon, where endogenous NOX1 is highly expressed. 24361341 7 70 theme NOX1 1197:1200 arg1 loop 1183:1186 the extracellular loop 1165:1186 the extracellular loop of mouse NOX1 1165:1200 Site-directed mutagenesis identified N-glycosylation sites at Asn(161) and Asn(241) on the extracellular loop of mouse NOX1. 24361341 9 71 link N-linked 1462:1469 arg1 glycosylation 1471:1483 N-linked glycosylation 1462:1483 N-linked glycosylation of murine NOX1 1462:1498 Taken together, these data identify the two specific sites of N-linked glycosylation of murine NOX1 and demonstrate that they are not required for normal enzyme activity, protein stability, and membrane trafficking. 24361341 1 72 theme Extensive 93:101 arg1 evidence 103:110 Extensive evidence 93:110 Extensive evidence 93:110 Extensive evidence demonstrates the pathophysiological importance of NOX1, the catalytic subunit of superoxide-generating enzyme NADPH oxidase, as a source of reactive oxygen species in nonphagocytic cells. 24361341 1 73 from species 268:274 arg1 cells 293:297 nonphagocytic cells 279:297 nonphagocytic cells 279:297 Extensive evidence demonstrates the pathophysiological importance of NOX1, the catalytic subunit of superoxide-generating enzyme NADPH oxidase, as a source of reactive oxygen species in nonphagocytic cells. 24361341 4 74 theme 60-90kDa 743:750 arg1 band 735:738 a broad band 727:738 a broad band of 60-90kDa 727:750 Immunoblots of lysates from cells expressing NOX1 revealed a doublet of 56 and 60kDa accompanied by a broad band of 60-90kDa. 24361341 8 75 from stability 1300:1308 arg1 protrusions 1387:1397 F-actin-positive membrane protrusions 1361:1397 F-actin-positive membrane protrusions 1361:1397 Elimination of N-glycosylation on NOX1 did not affect its electron transferase activity, protein stability, targeting to the cell surface, or localization in F-actin-positive membrane protrusions. 24361341 0 76 theme sites 36:40 arg1 Characterization 0:15 Characterization 0:15 Characterization of N-glycosylation sites on the extracellular domain of NOX1/NADPH oxidase. 0:91 Characterization of N-glycosylation sites on the extracellular domain of NOX1/NADPH oxidase. 24361341 4 77 from cells 655:659 arg1 lysates 642:648 lysates 642:648 lysates from cells expressing NOX1 642:675 Immunoblots of lysates from cells expressing NOX1 revealed a doublet of 56 and 60kDa accompanied by a broad band of 60-90kDa. 24361341 4 77 from cells 655:659 arg1 Immunoblots 627:637 Immunoblots 627:637 Immunoblots of lysates from cells expressing NOX1 627:675 Immunoblots of lysates from cells expressing NOX1 revealed a doublet of 56 and 60kDa accompanied by a broad band of 60-90kDa. 24361341 10 78 theme biologic 1686:1693 arg1 s 1704:1704 its biologic function(s) 1682:1705 its biologic function(s) 1682:1705 As is true for NOX2, the contribution of glycosylation in NOX1 to its biologic function(s) merits further study. 24361341 7 79 theme extracellular 1169:1181 arg1 loop 1183:1186 the extracellular loop 1165:1186 the extracellular loop of mouse NOX1 1165:1200 Site-directed mutagenesis identified N-glycosylation sites at Asn(161) and Asn(241) on the extracellular loop of mouse NOX1. 24361341 3 80 theme raised 447:452 arg1 antibody 470:477 a newly raised NOX1 polyclonal antibody 439:477 a newly raised NOX1 polyclonal antibody 439:477 We used a newly raised NOX1 polyclonal antibody to investigate posttranslational modifications of NOX1 overexpressed in cultured cells and in the colon, where endogenous NOX1 is highly expressed. 24361341 2 81 theme tools 424:428 arg1 lack 393:396 a lack 391:396 a lack of specific immunological tools 391:428 However, the biochemical properties of NOX1 have not been extensively characterized due to a lack of specific immunological tools. 24361341 0 82 gly N-glycosylation 20:34 arg2 sites 36:40 N-glycosylation sites 20:40 N-glycosylation sites 20:40 Characterization of N-glycosylation sites on the extracellular domain of NOX1/NADPH oxidase. 24361341 3 83 theme NOX1 529:532 arg1 modifications 512:524 posttranslational modifications 494:524 posttranslational modifications of NOX1 overexpressed in cultured cells and in the colon, where endogenous NOX1 is highly expressed 494:624 We used a newly raised NOX1 polyclonal antibody to investigate posttranslational modifications of NOX1 overexpressed in cultured cells and in the colon, where endogenous NOX1 is highly expressed. 24361341 3 84 used used 434:437 arg2 We 431:432 We 431:432 We 431:432 We used a newly raised NOX1 polyclonal antibody to investigate posttranslational modifications of NOX1 overexpressed in cultured cells and in the colon, where endogenous NOX1 is highly expressed. 24361341 2 85 theme specific 401:408 arg1 tools 424:428 specific immunological tools 401:428 specific immunological tools 401:428 However, the biochemical properties of NOX1 have not been extensively characterized due to a lack of specific immunological tools. 24361341 7 86 theme mouse 1191:1195 arg1 NOX1 1197:1200 mouse NOX1 1191:1200 mouse NOX1 1191:1200 Site-directed mutagenesis identified N-glycosylation sites at Asn(161) and Asn(241) on the extracellular loop of mouse NOX1. 24361341 1 87 theme oxygen 261:266 arg1 species 268:274 reactive oxygen species 252:274 reactive oxygen species in nonphagocytic cells 252:297 Extensive evidence demonstrates the pathophysiological importance of NOX1, the catalytic subunit of superoxide-generating enzyme NADPH oxidase, as a source of reactive oxygen species in nonphagocytic cells. 28733331 4 0 theme N-glycosylation 476:490 arg1 sites 492:496 two potential N-glycosylation sites 462:496 two potential N-glycosylation sites (Asn36 and Asn81) 462:514 In the present study, we analysed N-glycosylation sites of FNDC5 and found that two potential N-glycosylation sites (Asn36 and Asn81) could indeed be occupied by N-glycan. 28733331 4 0 theme N-glycosylation 476:490 arg1 Asn81 509:513 Asn81 509:513 Asn81 509:513 In the present study, we analysed N-glycosylation sites of FNDC5 and found that two potential N-glycosylation sites (Asn36 and Asn81) could indeed be occupied by N-glycan. 28733331 4 0 theme N-glycosylation 476:490 arg1 Asn36 499:503 Asn36 499:503 Asn36 499:503 In the present study, we analysed N-glycosylation sites of FNDC5 and found that two potential N-glycosylation sites (Asn36 and Asn81) could indeed be occupied by N-glycan. 28733331 4 1 used occupied 532:539 arg2 Asn36 499:503 Asn36 499:503 Asn36 499:503 In the present study, we analysed N-glycosylation sites of FNDC5 and found that two potential N-glycosylation sites (Asn36 and Asn81) could indeed be occupied by N-glycan. 28733331 4 1 used occupied 532:539 arg2 sites 492:496 two potential N-glycosylation sites 462:496 two potential N-glycosylation sites (Asn36 and Asn81) 462:514 In the present study, we analysed N-glycosylation sites of FNDC5 and found that two potential N-glycosylation sites (Asn36 and Asn81) could indeed be occupied by N-glycan. 28733331 4 1 used occupied 532:539 arg2 Asn81 509:513 Asn81 509:513 Asn81 509:513 In the present study, we analysed N-glycosylation sites of FNDC5 and found that two potential N-glycosylation sites (Asn36 and Asn81) could indeed be occupied by N-glycan. 28733331 5 2 theme signal 728:733 arg1 peptide 735:741 the signal peptide 724:741 the signal peptide 724:741 Furthermore we showed that the lack of N-glycosylation decreases the secretion of irisin, which is relevant to the instability of FNDC5 and the deficiency of cleavage of the signal peptide. 28733331 6 3 theme expression 767:776 arg1 level 778:782 the expression level 763:782 the expression level of N-glycosylated FNDC5 763:806 We also found that the expression level of N-glycosylated FNDC5 was elevated after myoblast differentiation. 28733331 5 4 theme irisin 636:641 arg1 relevant 653:660 relevant 653:660 relevant 653:660 Furthermore we showed that the lack of N-glycosylation decreases the secretion of irisin, which is relevant to the instability of FNDC5 and the deficiency of cleavage of the signal peptide. 28733331 5 4 theme irisin 636:641 arg1 secretion 623:631 the secretion 619:631 the secretion 619:631 Furthermore we showed that the lack of N-glycosylation decreases the secretion of irisin, which is relevant to the instability of FNDC5 and the deficiency of cleavage of the signal peptide. 28733331 4 5 gly N-glycosylation 416:430 arg2 FNDC5 441:445 FNDC5 441:445 FNDC5 441:445 In the present study, we analysed N-glycosylation sites of FNDC5 and found that two potential N-glycosylation sites (Asn36 and Asn81) could indeed be occupied by N-glycan. 28733331 4 5 gly N-glycosylation 416:430 arg1 FNDC5 441:445 FNDC5 441:445 FNDC5 441:445 In the present study, we analysed N-glycosylation sites of FNDC5 and found that two potential N-glycosylation sites (Asn36 and Asn81) could indeed be occupied by N-glycan. 28733331 4 5 gly N-glycosylation 416:430 arg2 sites 432:436 N-glycosylation sites 416:436 N-glycosylation sites of FNDC5 416:445 In the present study, we analysed N-glycosylation sites of FNDC5 and found that two potential N-glycosylation sites (Asn36 and Asn81) could indeed be occupied by N-glycan. 28733331 3 6 theme FNDC5 349:353 arg1 N-glycosylation 330:344 The N-glycosylation 326:344 The N-glycosylation of FNDC5 326:353 The N-glycosylation of FNDC5 remains poorly understood. 28733331 4 7 gly N-glycosylation 476:490 arg2 Asn36 499:503 Asn36 499:503 Asn36 499:503 In the present study, we analysed N-glycosylation sites of FNDC5 and found that two potential N-glycosylation sites (Asn36 and Asn81) could indeed be occupied by N-glycan. 28733331 4 7 gly N-glycosylation 476:490 arg2 sites 492:496 two potential N-glycosylation sites 462:496 two potential N-glycosylation sites (Asn36 and Asn81) 462:514 In the present study, we analysed N-glycosylation sites of FNDC5 and found that two potential N-glycosylation sites (Asn36 and Asn81) could indeed be occupied by N-glycan. 28733331 4 7 gly N-glycosylation 476:490 arg2 Asn81 509:513 Asn81 509:513 Asn81 509:513 In the present study, we analysed N-glycosylation sites of FNDC5 and found that two potential N-glycosylation sites (Asn36 and Asn81) could indeed be occupied by N-glycan. 28733331 4 7 gly N-glycosylation 476:490 arg2 two 462:464 two 462:464 two 462:464 In the present study, we analysed N-glycosylation sites of FNDC5 and found that two potential N-glycosylation sites (Asn36 and Asn81) could indeed be occupied by N-glycan. 28733331 5 8 theme deficiency 698:707 arg1 instability 669:679 the instability 665:679 the instability of FNDC5 and the deficiency of cleavage of the signal peptide 665:741 Furthermore we showed that the lack of N-glycosylation decreases the secretion of irisin, which is relevant to the instability of FNDC5 and the deficiency of cleavage of the signal peptide. 28733331 6 9 gly N-glycosylated 787:800 arg1 FNDC5 802:806 N-glycosylated FNDC5 787:806 N-glycosylated FNDC5 787:806 We also found that the expression level of N-glycosylated FNDC5 was elevated after myoblast differentiation. 28733331 4 10 theme present 389:395 arg1 study 397:401 the present study 385:401 the present study 385:401 In the present study, we analysed N-glycosylation sites of FNDC5 and found that two potential N-glycosylation sites (Asn36 and Asn81) could indeed be occupied by N-glycan. 28733331 4 11 theme potential 466:474 arg1 sites 492:496 two potential N-glycosylation sites 462:496 two potential N-glycosylation sites (Asn36 and Asn81) 462:514 In the present study, we analysed N-glycosylation sites of FNDC5 and found that two potential N-glycosylation sites (Asn36 and Asn81) could indeed be occupied by N-glycan. 28733331 4 11 theme potential 466:474 arg1 Asn81 509:513 Asn81 509:513 Asn81 509:513 In the present study, we analysed N-glycosylation sites of FNDC5 and found that two potential N-glycosylation sites (Asn36 and Asn81) could indeed be occupied by N-glycan. 28733331 4 11 theme potential 466:474 arg1 Asn36 499:503 Asn36 499:503 Asn36 499:503 In the present study, we analysed N-glycosylation sites of FNDC5 and found that two potential N-glycosylation sites (Asn36 and Asn81) could indeed be occupied by N-glycan. 28733331 5 12 theme N-glycosylation 593:607 arg1 lack 585:588 the lack 581:588 the lack of N-glycosylation 581:607 Furthermore we showed that the lack of N-glycosylation decreases the secretion of irisin, which is relevant to the instability of FNDC5 and the deficiency of cleavage of the signal peptide. 28733331 2 13 theme FNDC5 257:261 arg1 N-glycosylation 238:252 N-glycosylation 238:252 N-glycosylation of FNDC5 238:261 Biochemical data have shown that N-glycosylation of FNDC5 is unlikely to affect ligand or receptor activation of irisin. 28733331 2 14 gly N-glycosylation 238:252 arg1 irisin 318:323 irisin 318:323 irisin 318:323 Biochemical data have shown that N-glycosylation of FNDC5 is unlikely to affect ligand or receptor activation of irisin. 28733331 2 14 gly N-glycosylation 238:252 arg1 ligand 285:290 ligand or receptor activation 285:313 ligand 285:290 Biochemical data have shown that N-glycosylation of FNDC5 is unlikely to affect ligand or receptor activation of irisin. 28733331 2 14 gly N-glycosylation 238:252 arg1 FNDC5 257:261 FNDC5 257:261 FNDC5 257:261 Biochemical data have shown that N-glycosylation of FNDC5 is unlikely to affect ligand or receptor activation of irisin. 28733331 2 14 gly N-glycosylation 238:252 arg1 receptor 295:302 ligand or receptor activation 285:313 receptor 295:302 Biochemical data have shown that N-glycosylation of FNDC5 is unlikely to affect ligand or receptor activation of irisin. 28733331 2 15 theme receptor 295:302 arg1 activation 304:313 ligand or receptor activation 285:313 activation 304:313 Biochemical data have shown that N-glycosylation of FNDC5 is unlikely to affect ligand or receptor activation of irisin. 28733331 7 16 theme irisin 895:900 arg1 secretion 882:890 the secretion 878:890 the secretion of irisin 878:900 These findings show that the secretion of irisin is modulated by N-glycosylation, which in turn enhances our understanding of the secretion of glycosylated irisin. 28733331 2 17 theme ligand 285:290 arg1 activation 304:313 ligand or receptor activation 285:313 activation 304:313 Biochemical data have shown that N-glycosylation of FNDC5 is unlikely to affect ligand or receptor activation of irisin. 28733331 6 18 theme myoblast 827:834 arg1 differentiation 836:850 myoblast differentiation 827:850 myoblast differentiation 827:850 We also found that the expression level of N-glycosylated FNDC5 was elevated after myoblast differentiation. 28733331 1 19 theme white 183:187 arg1 tissue 197:202 white adipose tissue 183:202 white adipose tissue 183:202 Irisin, a myokine derived from the extracellular domain of FNDC5, has been shown to mediate thermogenesis of white adipose tissue. 28733331 5 20 theme peptide 735:741 arg1 cleavage 712:719 cleavage 712:719 cleavage of the signal peptide 712:741 Furthermore we showed that the lack of N-glycosylation decreases the secretion of irisin, which is relevant to the instability of FNDC5 and the deficiency of cleavage of the signal peptide. 28733331 2 21 theme irisin 318:323 arg1 activation 304:313 ligand or receptor activation 285:313 activation 304:313 Biochemical data have shown that N-glycosylation of FNDC5 is unlikely to affect ligand or receptor activation of irisin. 28733331 3 22 gly N-glycosylation 330:344 arg1 FNDC5 349:353 FNDC5 349:353 FNDC5 349:353 The N-glycosylation of FNDC5 remains poorly understood. 28733331 1 23 theme adipose 189:195 arg1 tissue 197:202 white adipose tissue 183:202 white adipose tissue 183:202 Irisin, a myokine derived from the extracellular domain of FNDC5, has been shown to mediate thermogenesis of white adipose tissue. 28733331 0 24 theme FDNC5 32:36 arg1 stabilization 38:50 FDNC5 stabilization 32:50 FDNC5 stabilization 32:50 N-Glycosylation is required for FDNC5 stabilization and irisin secretion. 28733331 5 25 theme FNDC5 684:688 arg1 instability 669:679 the instability 665:679 the instability of FNDC5 and the deficiency of cleavage of the signal peptide 665:741 Furthermore we showed that the lack of N-glycosylation decreases the secretion of irisin, which is relevant to the instability of FNDC5 and the deficiency of cleavage of the signal peptide. 28733331 1 26 theme tissue 197:202 arg1 thermogenesis 166:178 thermogenesis 166:178 thermogenesis of white adipose tissue 166:202 Irisin, a myokine derived from the extracellular domain of FNDC5, has been shown to mediate thermogenesis of white adipose tissue. 28733331 0 27 theme irisin 56:61 arg1 secretion 63:71 irisin secretion 56:71 irisin secretion 56:71 N-Glycosylation is required for FDNC5 stabilization and irisin secretion. 28733331 7 28 theme irisin 1009:1014 arg1 secretion 983:991 the secretion 979:991 the secretion of glycosylated irisin 979:1014 These findings show that the secretion of irisin is modulated by N-glycosylation, which in turn enhances our understanding of the secretion of glycosylated irisin. 28733331 4 29 theme FNDC5 441:445 arg1 FNDC5 441:445 FNDC5 441:445 FNDC5 441:445 In the present study, we analysed N-glycosylation sites of FNDC5 and found that two potential N-glycosylation sites (Asn36 and Asn81) could indeed be occupied by N-glycan. 28733331 4 29 theme FNDC5 441:445 arg1 sites 432:436 N-glycosylation sites 416:436 N-glycosylation sites of FNDC5 416:445 In the present study, we analysed N-glycosylation sites of FNDC5 and found that two potential N-glycosylation sites (Asn36 and Asn81) could indeed be occupied by N-glycan. 28733331 2 30 theme Biochemical 205:215 arg1 data 217:220 Biochemical data 205:220 Biochemical data 205:220 Biochemical data have shown that N-glycosylation of FNDC5 is unlikely to affect ligand or receptor activation of irisin. 28733331 7 31 theme secretion 983:991 arg1 understanding 962:974 our understanding 958:974 our understanding of the secretion of glycosylated irisin 958:1014 These findings show that the secretion of irisin is modulated by N-glycosylation, which in turn enhances our understanding of the secretion of glycosylated irisin. 28733331 4 32 dep sites 492:496 arg1 sites 492:496 two potential N-glycosylation sites 462:496 two potential N-glycosylation sites (Asn36 and Asn81) 462:514 In the present study, we analysed N-glycosylation sites of FNDC5 and found that two potential N-glycosylation sites (Asn36 and Asn81) could indeed be occupied by N-glycan. 28733331 4 32 dep sites 492:496 arg1 Asn81 509:513 Asn81 509:513 Asn81 509:513 In the present study, we analysed N-glycosylation sites of FNDC5 and found that two potential N-glycosylation sites (Asn36 and Asn81) could indeed be occupied by N-glycan. 28733331 4 32 dep sites 492:496 arg1 Asn36 499:503 Asn36 499:503 Asn36 499:503 In the present study, we analysed N-glycosylation sites of FNDC5 and found that two potential N-glycosylation sites (Asn36 and Asn81) could indeed be occupied by N-glycan. 28733331 6 33 theme FNDC5 802:806 arg1 level 778:782 the expression level 763:782 the expression level of N-glycosylated FNDC5 763:806 We also found that the expression level of N-glycosylated FNDC5 was elevated after myoblast differentiation. 28733331 1 34 theme extracellular 109:121 arg1 domain 123:128 the extracellular domain 105:128 the extracellular domain of FNDC5 105:137 Irisin, a myokine derived from the extracellular domain of FNDC5, has been shown to mediate thermogenesis of white adipose tissue. 28733331 1 34 theme extracellular 109:121 arg1 FNDC5 133:137 FNDC5 133:137 FNDC5 133:137 Irisin, a myokine derived from the extracellular domain of FNDC5, has been shown to mediate thermogenesis of white adipose tissue. 28733331 1 35 attach derived 92:98 arg1 domain 123:128 the extracellular domain 105:128 the extracellular domain of FNDC5 105:137 Irisin, a myokine derived from the extracellular domain of FNDC5, has been shown to mediate thermogenesis of white adipose tissue. 28733331 1 35 attach derived 92:98 arg2 myokine 84:90 a myokine 82:90 a myokine derived from the extracellular domain of FNDC5 82:137 Irisin, a myokine derived from the extracellular domain of FNDC5, has been shown to mediate thermogenesis of white adipose tissue. 28733331 1 35 attach derived 92:98 arg1 FNDC5 133:137 FNDC5 133:137 FNDC5 133:137 Irisin, a myokine derived from the extracellular domain of FNDC5, has been shown to mediate thermogenesis of white adipose tissue. 28733331 1 35 attach derived 92:98 arg2 Irisin 74:79 Irisin 74:79 Irisin 74:79 Irisin, a myokine derived from the extracellular domain of FNDC5, has been shown to mediate thermogenesis of white adipose tissue. 28733331 6 36 theme N-glycosylated 787:800 arg1 FNDC5 802:806 N-glycosylated FNDC5 787:806 N-glycosylated FNDC5 787:806 We also found that the expression level of N-glycosylated FNDC5 was elevated after myoblast differentiation. 28733331 7 37 gly glycosylated 996:1007 arg1 irisin 1009:1014 glycosylated irisin 996:1014 glycosylated irisin 996:1014 These findings show that the secretion of irisin is modulated by N-glycosylation, which in turn enhances our understanding of the secretion of glycosylated irisin. 28733331 7 38 theme glycosylated 996:1007 arg1 irisin 1009:1014 glycosylated irisin 996:1014 glycosylated irisin 996:1014 These findings show that the secretion of irisin is modulated by N-glycosylation, which in turn enhances our understanding of the secretion of glycosylated irisin. 28733331 4 39 theme N-glycosylation 416:430 arg1 FNDC5 441:445 FNDC5 441:445 FNDC5 441:445 In the present study, we analysed N-glycosylation sites of FNDC5 and found that two potential N-glycosylation sites (Asn36 and Asn81) could indeed be occupied by N-glycan. 28733331 4 39 theme N-glycosylation 416:430 arg1 sites 432:436 N-glycosylation sites 416:436 N-glycosylation sites of FNDC5 416:445 In the present study, we analysed N-glycosylation sites of FNDC5 and found that two potential N-glycosylation sites (Asn36 and Asn81) could indeed be occupied by N-glycan. 28733331 5 40 theme cleavage 712:719 arg1 deficiency 698:707 the deficiency 694:707 the deficiency of cleavage of the signal peptide 694:741 Furthermore we showed that the lack of N-glycosylation decreases the secretion of irisin, which is relevant to the instability of FNDC5 and the deficiency of cleavage of the signal peptide. 28733331 5 40 theme cleavage 712:719 arg1 FNDC5 684:688 FNDC5 684:688 FNDC5 684:688 Furthermore we showed that the lack of N-glycosylation decreases the secretion of irisin, which is relevant to the instability of FNDC5 and the deficiency of cleavage of the signal peptide. 28733331 1 41 theme FNDC5 133:137 arg1 domain 123:128 the extracellular domain 105:128 the extracellular domain of FNDC5 105:137 Irisin, a myokine derived from the extracellular domain of FNDC5, has been shown to mediate thermogenesis of white adipose tissue. 28733331 1 41 theme FNDC5 133:137 arg1 FNDC5 133:137 FNDC5 133:137 FNDC5 133:137 Irisin, a myokine derived from the extracellular domain of FNDC5, has been shown to mediate thermogenesis of white adipose tissue. 25898205 3 0 theme biological 627:636 arg1 activity 638:645 its biological activity 623:645 its biological activity 623:645 In this study, we introduced N-glycosylation sites into wild-type xlEPO at the positions homologous to those in huEPO, and tested whether the glycosylated mutein retained its biological activity. 25898205 1 1 theme several 239:245 arg1 mammals 253:259 several other mammals 239:259 several other mammals 239:259 Erythropoietin (EPO), the primary regulator of erythropoiesis, is a heavily glycosylated protein found in humans and several other mammals. 25898205 9 2 theme biological 1610:1619 arg1 activity 1621:1628 biological activity 1610:1628 biological activity 1610:1628 Hence, the EPO-EPOR binding site in X. laevis locates the distal region of artificially introduced three N-glycosylation sites, demonstrating that the vital conformation to exert biological activity is conserved between humans and X. laevis, despite the low similarity in primary structures of EPO and EPOR. 25898205 2 3 from EPO 306:308 arg1 xlEPO 329:333 xlEPO 329:333 xlEPO 329:333 Intriguingly, we have previously found that EPO in Xenopus laevis (xlEPO) has no N-glycosylation sites, and cross-reacts with the human EPO (huEPO) receptor despite low homology with huEPO. 25898205 2 3 from EPO 306:308 arg1 laevis 321:326 Xenopus laevis 313:326 Xenopus laevis (xlEPO) 313:334 Intriguingly, we have previously found that EPO in Xenopus laevis (xlEPO) has no N-glycosylation sites, and cross-reacts with the human EPO (huEPO) receptor despite low homology with huEPO. 25898205 8 4 from effect 1163:1168 arg1 proliferation 1187:1199 xlEPOR-FDC/P2 proliferation 1173:1199 xlEPOR-FDC/P2 proliferation 1173:1199 The maximum effect on xlEPOR-FDC/P2 proliferation was decreased by the addition of N-linked carbohydrates, but that on UT-7/EPO proliferation was not changed, indicating that the muteins act as partial agonists to the xlEPO receptor, and near-full agonists to the huEPO receptor. 25898205 5 5 theme secretion 809:817 arg1 efficiency 819:828 lower secretion efficiency 803:828 lower secretion efficiency 803:828 The muteins exhibited lower secretion efficiency, higher hydrophilicity, and stronger acidic properties than the wild type. 25898205 8 6 theme maximum 1155:1161 arg1 effect 1163:1168 The maximum effect 1151:1168 The maximum effect on xlEPOR-FDC/P2 proliferation 1151:1199 The maximum effect on xlEPOR-FDC/P2 proliferation was decreased by the addition of N-linked carbohydrates, but that on UT-7/EPO proliferation was not changed, indicating that the muteins act as partial agonists to the xlEPO receptor, and near-full agonists to the huEPO receptor. 25898205 3 7 theme wild-type 508:516 arg1 xlEPO 518:522 wild-type xlEPO 508:522 wild-type xlEPO at the positions homologous to those in huEPO 508:568 In this study, we introduced N-glycosylation sites into wild-type xlEPO at the positions homologous to those in huEPO, and tested whether the glycosylated mutein retained its biological activity. 25898205 8 8 theme near-full 1389:1397 arg1 agonists 1399:1406 the xlEPO receptor, and near-full agonists 1365:1406 agonists 1399:1406 The maximum effect on xlEPOR-FDC/P2 proliferation was decreased by the addition of N-linked carbohydrates, but that on UT-7/EPO proliferation was not changed, indicating that the muteins act as partial agonists to the xlEPO receptor, and near-full agonists to the huEPO receptor. 25898205 8 9 theme carbohydrates 1243:1255 arg1 addition 1222:1229 the addition 1218:1229 the addition of N-linked carbohydrates 1218:1255 The maximum effect on xlEPOR-FDC/P2 proliferation was decreased by the addition of N-linked carbohydrates, but that on UT-7/EPO proliferation was not changed, indicating that the muteins act as partial agonists to the xlEPO receptor, and near-full agonists to the huEPO receptor. 25898205 1 10 theme glycosylated 198:209 arg1 protein 211:217 a heavily glycosylated protein 188:217 a heavily glycosylated protein found in humans and several other mammals 188:259 Erythropoietin (EPO), the primary regulator of erythropoiesis, is a heavily glycosylated protein found in humans and several other mammals. 25898205 1 10 theme glycosylated 198:209 arg1 Erythropoietin 122:135 Erythropoietin 122:135 Erythropoietin (EPO) 122:141 Erythropoietin (EPO), the primary regulator of erythropoiesis, is a heavily glycosylated protein found in humans and several other mammals. 25898205 9 11 theme low 1685:1687 arg1 similarity 1689:1698 the low similarity 1681:1698 the low similarity in primary structures of EPO and EPOR 1681:1736 Hence, the EPO-EPOR binding site in X. laevis locates the distal region of artificially introduced three N-glycosylation sites, demonstrating that the vital conformation to exert biological activity is conserved between humans and X. laevis, despite the low similarity in primary structures of EPO and EPOR. 25898205 8 12 theme huEPO 1415:1419 arg1 receptor 1421:1428 the huEPO receptor 1411:1428 the huEPO receptor 1411:1428 The maximum effect on xlEPOR-FDC/P2 proliferation was decreased by the addition of N-linked carbohydrates, but that on UT-7/EPO proliferation was not changed, indicating that the muteins act as partial agonists to the xlEPO receptor, and near-full agonists to the huEPO receptor. 25898205 9 13 theme introduced 1519:1528 arg1 sites 1552:1556 artificially introduced three N-glycosylation sites 1506:1556 artificially introduced three N-glycosylation sites 1506:1556 Hence, the EPO-EPOR binding site in X. laevis locates the distal region of artificially introduced three N-glycosylation sites, demonstrating that the vital conformation to exert biological activity is conserved between humans and X. laevis, despite the low similarity in primary structures of EPO and EPOR. 25898205 5 14 theme acidic 867:872 arg1 properties 874:883 stronger acidic properties 858:883 stronger acidic properties 858:883 The muteins exhibited lower secretion efficiency, higher hydrophilicity, and stronger acidic properties than the wild type. 25898205 5 15 theme stronger 858:865 arg1 properties 874:883 stronger acidic properties 858:883 stronger acidic properties 858:883 The muteins exhibited lower secretion efficiency, higher hydrophilicity, and stronger acidic properties than the wild type. 25898205 1 16 theme primary 148:154 arg1 regulator 156:164 the primary regulator 144:164 the primary regulator of erythropoiesis 144:182 Erythropoietin (EPO), the primary regulator of erythropoiesis, is a heavily glycosylated protein found in humans and several other mammals. 25898205 1 16 theme primary 148:154 arg1 Erythropoietin 122:135 Erythropoietin 122:135 Erythropoietin (EPO) 122:141 Erythropoietin (EPO), the primary regulator of erythropoiesis, is a heavily glycosylated protein found in humans and several other mammals. 25898205 9 17 theme EPO 1725:1727 arg1 structures 1711:1720 primary structures 1703:1720 primary structures of EPO and EPOR 1703:1736 Hence, the EPO-EPOR binding site in X. laevis locates the distal region of artificially introduced three N-glycosylation sites, demonstrating that the vital conformation to exert biological activity is conserved between humans and X. laevis, despite the low similarity in primary structures of EPO and EPOR. 25898205 9 18 theme binding 1451:1457 arg1 site 1459:1462 the EPO-EPOR binding site 1438:1462 the EPO-EPOR binding site in X. laevis 1438:1475 Hence, the EPO-EPOR binding site in X. laevis locates the distal region of artificially introduced three N-glycosylation sites, demonstrating that the vital conformation to exert biological activity is conserved between humans and X. laevis, despite the low similarity in primary structures of EPO and EPOR. 25898205 9 19 theme EPOR 1733:1736 arg1 structures 1711:1720 primary structures 1703:1720 primary structures of EPO and EPOR 1703:1736 Hence, the EPO-EPOR binding site in X. laevis locates the distal region of artificially introduced three N-glycosylation sites, demonstrating that the vital conformation to exert biological activity is conserved between humans and X. laevis, despite the low similarity in primary structures of EPO and EPOR. 25898205 0 20 theme laevis 99:104 arg1 erythropoietin 106:119 Xenopus laevis erythropoietin 91:119 Xenopus laevis erythropoietin 91:119 The influence of artificially introduced N-glycosylation sites on the in vitro activity of Xenopus laevis erythropoietin. 25898205 6 21 theme lines 959:963 arg1 proliferation 932:944 the proliferation 928:944 the proliferation of both cell lines, xlEPO receptor-expressing xlEPOR-FDC/P2 cells and huEPO receptor-expressing UT-7/EPO cells 928:1055 All muteins stimulated the proliferation of both cell lines, xlEPO receptor-expressing xlEPOR-FDC/P2 cells and huEPO receptor-expressing UT-7/EPO cells, in a dose-dependent manner. 25898205 6 22 theme receptor-expressing 1022:1040 arg1 cells 1051:1055 huEPO receptor-expressing UT-7/EPO cells 1016:1055 huEPO receptor-expressing UT-7/EPO cells 1016:1055 All muteins stimulated the proliferation of both cell lines, xlEPO receptor-expressing xlEPOR-FDC/P2 cells and huEPO receptor-expressing UT-7/EPO cells, in a dose-dependent manner. 25898205 2 23 theme huEPO 403:407 arg1 receptor 410:417 the human EPO (huEPO) receptor 388:417 the human EPO (huEPO) receptor 388:417 Intriguingly, we have previously found that EPO in Xenopus laevis (xlEPO) has no N-glycosylation sites, and cross-reacts with the human EPO (huEPO) receptor despite low homology with huEPO. 25898205 4 24 theme additional 684:693 arg1 carbohydrates 704:716 1-3 additional N-linked carbohydrates 680:716 1-3 additional N-linked carbohydrates 680:716 Seven xlEPO muteins, containing 1-3 additional N-linked carbohydrates at positions 24, 38, and/or 83, were expressed in COS-1 cells. 25898205 2 25 theme N-glycosylation 343:357 arg1 sites 359:363 no N-glycosylation sites 340:363 no N-glycosylation sites 340:363 Intriguingly, we have previously found that EPO in Xenopus laevis (xlEPO) has no N-glycosylation sites, and cross-reacts with the human EPO (huEPO) receptor despite low homology with huEPO. 25898205 7 26 theme biological 1128:1137 arg1 activities 1139:1148 their in vitro biological activities 1113:1148 their in vitro biological activities 1113:1148 Thus, the muteins retained their in vitro biological activities. 25898205 3 27 gly N-glycosylation 481:495 arg2 sites 497:501 N-glycosylation sites 481:501 N-glycosylation sites 481:501 In this study, we introduced N-glycosylation sites into wild-type xlEPO at the positions homologous to those in huEPO, and tested whether the glycosylated mutein retained its biological activity. 25898205 2 28 theme EPO 398:400 arg1 receptor 410:417 the human EPO (huEPO) receptor 388:417 the human EPO (huEPO) receptor 388:417 Intriguingly, we have previously found that EPO in Xenopus laevis (xlEPO) has no N-glycosylation sites, and cross-reacts with the human EPO (huEPO) receptor despite low homology with huEPO. 25898205 1 29 located found 219:223 arg2 protein 211:217 a heavily glycosylated protein 188:217 a heavily glycosylated protein found in humans and several other mammals 188:259 Erythropoietin (EPO), the primary regulator of erythropoiesis, is a heavily glycosylated protein found in humans and several other mammals. 25898205 1 29 located found 219:223 arg1 humans 228:233 humans 228:233 humans 228:233 Erythropoietin (EPO), the primary regulator of erythropoiesis, is a heavily glycosylated protein found in humans and several other mammals. 25898205 1 29 located found 219:223 arg2 Erythropoietin 122:135 Erythropoietin 122:135 Erythropoietin (EPO) 122:141 Erythropoietin (EPO), the primary regulator of erythropoiesis, is a heavily glycosylated protein found in humans and several other mammals. 25898205 1 29 located found 219:223 arg1 mammals 253:259 several other mammals 239:259 several other mammals 239:259 Erythropoietin (EPO), the primary regulator of erythropoiesis, is a heavily glycosylated protein found in humans and several other mammals. 25898205 7 30 theme in 1119:1120 arg1 activities 1139:1148 their in vitro biological activities 1113:1148 their in vitro biological activities 1113:1148 Thus, the muteins retained their in vitro biological activities. 25898205 5 31 theme wild 894:897 arg1 type 899:902 the wild type 890:902 the wild type 890:902 The muteins exhibited lower secretion efficiency, higher hydrophilicity, and stronger acidic properties than the wild type. 25898205 6 32 theme xlEPOR-FDC/P2 992:1004 arg1 cells 1006:1010 xlEPO receptor-expressing xlEPOR-FDC/P2 cells 966:1010 xlEPO receptor-expressing xlEPOR-FDC/P2 cells 966:1010 All muteins stimulated the proliferation of both cell lines, xlEPO receptor-expressing xlEPOR-FDC/P2 cells and huEPO receptor-expressing UT-7/EPO cells, in a dose-dependent manner. 25898205 2 33 theme low 427:429 arg1 homology 431:438 low homology 427:438 low homology with huEPO 427:449 Intriguingly, we have previously found that EPO in Xenopus laevis (xlEPO) has no N-glycosylation sites, and cross-reacts with the human EPO (huEPO) receptor despite low homology with huEPO. 25898205 0 34 theme introduced 30:39 arg1 sites 57:61 artificially introduced N-glycosylation sites 17:61 artificially introduced N-glycosylation sites 17:61 The influence of artificially introduced N-glycosylation sites on the in vitro activity of Xenopus laevis erythropoietin. 25898205 9 35 theme sites 1552:1556 arg1 region 1496:1501 the distal region 1485:1501 the distal region of artificially introduced three N-glycosylation sites 1485:1556 Hence, the EPO-EPOR binding site in X. laevis locates the distal region of artificially introduced three N-glycosylation sites, demonstrating that the vital conformation to exert biological activity is conserved between humans and X. laevis, despite the low similarity in primary structures of EPO and EPOR. 25898205 6 36 theme xlEPO 966:970 arg1 cells 1006:1010 xlEPO receptor-expressing xlEPOR-FDC/P2 cells 966:1010 xlEPO receptor-expressing xlEPOR-FDC/P2 cells 966:1010 All muteins stimulated the proliferation of both cell lines, xlEPO receptor-expressing xlEPOR-FDC/P2 cells and huEPO receptor-expressing UT-7/EPO cells, in a dose-dependent manner. 25898205 0 37 theme sites 57:61 arg1 influence 4:12 The influence 0:12 The influence of artificially introduced N-glycosylation sites on the in vitro activity of Xenopus laevis erythropoietin 0:119 The influence of artificially introduced N-glycosylation sites on the in vitro activity of Xenopus laevis erythropoietin. 25898205 0 38 gly N-glycosylation 41:55 arg2 sites 57:61 artificially introduced N-glycosylation sites 17:61 artificially introduced N-glycosylation sites 17:61 The influence of artificially introduced N-glycosylation sites on the in vitro activity of Xenopus laevis erythropoietin. 25898205 6 39 theme dose-dependent 1063:1076 arg1 manner 1078:1083 a dose-dependent manner 1061:1083 a dose-dependent manner 1061:1083 All muteins stimulated the proliferation of both cell lines, xlEPO receptor-expressing xlEPOR-FDC/P2 cells and huEPO receptor-expressing UT-7/EPO cells, in a dose-dependent manner. 25898205 9 40 gly N-glycosylation 1536:1550 arg2 three 1530:1534 three 1530:1534 three 1530:1534 Hence, the EPO-EPOR binding site in X. laevis locates the distal region of artificially introduced three N-glycosylation sites, demonstrating that the vital conformation to exert biological activity is conserved between humans and X. laevis, despite the low similarity in primary structures of EPO and EPOR. 25898205 9 40 gly N-glycosylation 1536:1550 arg2 sites 1552:1556 artificially introduced three N-glycosylation sites 1506:1556 artificially introduced three N-glycosylation sites 1506:1556 Hence, the EPO-EPOR binding site in X. laevis locates the distal region of artificially introduced three N-glycosylation sites, demonstrating that the vital conformation to exert biological activity is conserved between humans and X. laevis, despite the low similarity in primary structures of EPO and EPOR. 25898205 9 41 from similarity 1689:1698 arg1 structures 1711:1720 primary structures 1703:1720 primary structures of EPO and EPOR 1703:1736 Hence, the EPO-EPOR binding site in X. laevis locates the distal region of artificially introduced three N-glycosylation sites, demonstrating that the vital conformation to exert biological activity is conserved between humans and X. laevis, despite the low similarity in primary structures of EPO and EPOR. 25898205 4 42 link N-linked 695:702 arg1 carbohydrates 704:716 1-3 additional N-linked carbohydrates 680:716 1-3 additional N-linked carbohydrates 680:716 Seven xlEPO muteins, containing 1-3 additional N-linked carbohydrates at positions 24, 38, and/or 83, were expressed in COS-1 cells. 25898205 3 43 gly glycosylated 594:605 arg1 mutein 607:612 the glycosylated mutein 590:612 the glycosylated mutein 590:612 In this study, we introduced N-glycosylation sites into wild-type xlEPO at the positions homologous to those in huEPO, and tested whether the glycosylated mutein retained its biological activity. 25898205 6 44 theme cells 1051:1055 arg1 proliferation 932:944 the proliferation 928:944 the proliferation of both cell lines, xlEPO receptor-expressing xlEPOR-FDC/P2 cells and huEPO receptor-expressing UT-7/EPO cells 928:1055 All muteins stimulated the proliferation of both cell lines, xlEPO receptor-expressing xlEPOR-FDC/P2 cells and huEPO receptor-expressing UT-7/EPO cells, in a dose-dependent manner. 25898205 3 45 theme N-glycosylation 481:495 arg1 sites 497:501 N-glycosylation sites 481:501 N-glycosylation sites 481:501 In this study, we introduced N-glycosylation sites into wild-type xlEPO at the positions homologous to those in huEPO, and tested whether the glycosylated mutein retained its biological activity. 25898205 1 46 theme other 247:251 arg1 mammals 253:259 several other mammals 239:259 several other mammals 239:259 Erythropoietin (EPO), the primary regulator of erythropoiesis, is a heavily glycosylated protein found in humans and several other mammals. 25898205 9 47 from site 1459:1462 arg1 laevis 1470:1475 X. laevis 1467:1475 X. laevis 1467:1475 Hence, the EPO-EPOR binding site in X. laevis locates the distal region of artificially introduced three N-glycosylation sites, demonstrating that the vital conformation to exert biological activity is conserved between humans and X. laevis, despite the low similarity in primary structures of EPO and EPOR. 25898205 9 48 theme X. 1467:1468 arg1 laevis 1470:1475 X. laevis 1467:1475 X. laevis 1467:1475 Hence, the EPO-EPOR binding site in X. laevis locates the distal region of artificially introduced three N-glycosylation sites, demonstrating that the vital conformation to exert biological activity is conserved between humans and X. laevis, despite the low similarity in primary structures of EPO and EPOR. 25898205 4 49 contain containing 669:678 arg1 muteins 660:666 Seven xlEPO muteins 648:666 Seven xlEPO muteins 648:666 Seven xlEPO muteins, containing 1-3 additional N-linked carbohydrates at positions 24, 38, and/or 83, were expressed in COS-1 cells. 25898205 4 49 contain containing 669:678 arg2 carbohydrates 704:716 1-3 additional N-linked carbohydrates 680:716 1-3 additional N-linked carbohydrates 680:716 Seven xlEPO muteins, containing 1-3 additional N-linked carbohydrates at positions 24, 38, and/or 83, were expressed in COS-1 cells. 25898205 5 50 theme lower 803:807 arg1 efficiency 819:828 lower secretion efficiency 803:828 lower secretion efficiency 803:828 The muteins exhibited lower secretion efficiency, higher hydrophilicity, and stronger acidic properties than the wild type. 25898205 4 51 theme COS-1 768:772 arg1 cells 774:778 COS-1 cells 768:778 COS-1 cells 768:778 Seven xlEPO muteins, containing 1-3 additional N-linked carbohydrates at positions 24, 38, and/or 83, were expressed in COS-1 cells. 25898205 1 52 gly glycosylated 198:209 arg1 protein 211:217 a heavily glycosylated protein 188:217 a heavily glycosylated protein found in humans and several other mammals 188:259 Erythropoietin (EPO), the primary regulator of erythropoiesis, is a heavily glycosylated protein found in humans and several other mammals. 25898205 1 52 gly glycosylated 198:209 arg1 Erythropoietin 122:135 Erythropoietin 122:135 Erythropoietin (EPO) 122:141 Erythropoietin (EPO), the primary regulator of erythropoiesis, is a heavily glycosylated protein found in humans and several other mammals. 25898205 1 53 theme erythropoiesis 169:182 arg1 regulator 156:164 the primary regulator 144:164 the primary regulator of erythropoiesis 144:182 Erythropoietin (EPO), the primary regulator of erythropoiesis, is a heavily glycosylated protein found in humans and several other mammals. 25898205 1 53 theme erythropoiesis 169:182 arg1 Erythropoietin 122:135 Erythropoietin 122:135 Erythropoietin (EPO) 122:141 Erythropoietin (EPO), the primary regulator of erythropoiesis, is a heavily glycosylated protein found in humans and several other mammals. 25898205 9 54 theme X. 1662:1663 arg1 laevis 1665:1670 X. laevis 1662:1670 X. laevis 1662:1670 Hence, the EPO-EPOR binding site in X. laevis locates the distal region of artificially introduced three N-glycosylation sites, demonstrating that the vital conformation to exert biological activity is conserved between humans and X. laevis, despite the low similarity in primary structures of EPO and EPOR. 25898205 9 55 dep conformation 1588:1599 arg1 exert 1604:1608 exert 1604:1608 to exert biological activity 1601:1628 Hence, the EPO-EPOR binding site in X. laevis locates the distal region of artificially introduced three N-glycosylation sites, demonstrating that the vital conformation to exert biological activity is conserved between humans and X. laevis, despite the low similarity in primary structures of EPO and EPOR. 25898205 3 56 theme homologous 541:550 arg1 positions 531:539 the positions 527:539 the positions homologous to those in huEPO 527:568 In this study, we introduced N-glycosylation sites into wild-type xlEPO at the positions homologous to those in huEPO, and tested whether the glycosylated mutein retained its biological activity. 25898205 8 57 theme N-linked 1234:1241 arg1 carbohydrates 1243:1255 N-linked carbohydrates 1234:1255 N-linked carbohydrates 1234:1255 The maximum effect on xlEPOR-FDC/P2 proliferation was decreased by the addition of N-linked carbohydrates, but that on UT-7/EPO proliferation was not changed, indicating that the muteins act as partial agonists to the xlEPO receptor, and near-full agonists to the huEPO receptor. 25898205 8 58 theme xlEPOR-FDC/P2 1173:1185 arg1 proliferation 1187:1199 xlEPOR-FDC/P2 proliferation 1173:1199 xlEPOR-FDC/P2 proliferation 1173:1199 The maximum effect on xlEPOR-FDC/P2 proliferation was decreased by the addition of N-linked carbohydrates, but that on UT-7/EPO proliferation was not changed, indicating that the muteins act as partial agonists to the xlEPO receptor, and near-full agonists to the huEPO receptor. 25898205 4 59 theme xlEPO 654:658 arg1 muteins 660:666 Seven xlEPO muteins 648:666 Seven xlEPO muteins 648:666 Seven xlEPO muteins, containing 1-3 additional N-linked carbohydrates at positions 24, 38, and/or 83, were expressed in COS-1 cells. 25898205 9 60 theme EPO-EPOR 1442:1449 arg1 site 1459:1462 the EPO-EPOR binding site 1438:1462 the EPO-EPOR binding site in X. laevis 1438:1475 Hence, the EPO-EPOR binding site in X. laevis locates the distal region of artificially introduced three N-glycosylation sites, demonstrating that the vital conformation to exert biological activity is conserved between humans and X. laevis, despite the low similarity in primary structures of EPO and EPOR. 25898205 0 61 theme in 70:71 arg1 activity 79:86 the in vitro activity 66:86 the in vitro activity of Xenopus laevis erythropoietin 66:119 The influence of artificially introduced N-glycosylation sites on the in vitro activity of Xenopus laevis erythropoietin. 25898205 6 62 theme cell 954:957 arg1 lines 959:963 both cell lines 949:963 both cell lines 949:963 All muteins stimulated the proliferation of both cell lines, xlEPO receptor-expressing xlEPOR-FDC/P2 cells and huEPO receptor-expressing UT-7/EPO cells, in a dose-dependent manner. 25898205 9 63 theme primary 1703:1709 arg1 structures 1711:1720 primary structures 1703:1720 primary structures of EPO and EPOR 1703:1736 Hence, the EPO-EPOR binding site in X. laevis locates the distal region of artificially introduced three N-glycosylation sites, demonstrating that the vital conformation to exert biological activity is conserved between humans and X. laevis, despite the low similarity in primary structures of EPO and EPOR. 25898205 8 64 theme UT-7/EPO 1270:1277 arg1 proliferation 1279:1291 UT-7/EPO proliferation 1270:1291 UT-7/EPO proliferation 1270:1291 The maximum effect on xlEPOR-FDC/P2 proliferation was decreased by the addition of N-linked carbohydrates, but that on UT-7/EPO proliferation was not changed, indicating that the muteins act as partial agonists to the xlEPO receptor, and near-full agonists to the huEPO receptor. 25898205 5 65 theme higher 831:836 arg1 hydrophilicity 838:851 higher hydrophilicity 831:851 higher hydrophilicity 831:851 The muteins exhibited lower secretion efficiency, higher hydrophilicity, and stronger acidic properties than the wild type. 25898205 0 66 from influence 4:12 arg1 activity 79:86 the in vitro activity 66:86 the in vitro activity of Xenopus laevis erythropoietin 66:119 The influence of artificially introduced N-glycosylation sites on the in vitro activity of Xenopus laevis erythropoietin. 25898205 7 67 dep in 1119:1120 arg1 vitro 1122:1126 vitro 1122:1126 vitro 1122:1126 Thus, the muteins retained their in vitro biological activities. 25898205 0 68 theme Xenopus 91:97 arg1 laevis 99:104 Xenopus laevis 91:104 Xenopus laevis erythropoietin 91:119 The influence of artificially introduced N-glycosylation sites on the in vitro activity of Xenopus laevis erythropoietin. 25898205 2 69 with homology 431:438 arg1 huEPO 445:449 huEPO 445:449 huEPO 445:449 Intriguingly, we have previously found that EPO in Xenopus laevis (xlEPO) has no N-glycosylation sites, and cross-reacts with the human EPO (huEPO) receptor despite low homology with huEPO. 25898205 0 70 theme erythropoietin 106:119 arg1 activity 79:86 the in vitro activity 66:86 the in vitro activity of Xenopus laevis erythropoietin 66:119 The influence of artificially introduced N-glycosylation sites on the in vitro activity of Xenopus laevis erythropoietin. 25898205 9 71 theme distal 1489:1494 arg1 region 1496:1501 the distal region 1485:1501 the distal region of artificially introduced three N-glycosylation sites 1485:1556 Hence, the EPO-EPOR binding site in X. laevis locates the distal region of artificially introduced three N-glycosylation sites, demonstrating that the vital conformation to exert biological activity is conserved between humans and X. laevis, despite the low similarity in primary structures of EPO and EPOR. 25898205 6 72 theme UT-7/EPO 1042:1049 arg1 cells 1051:1055 huEPO receptor-expressing UT-7/EPO cells 1016:1055 huEPO receptor-expressing UT-7/EPO cells 1016:1055 All muteins stimulated the proliferation of both cell lines, xlEPO receptor-expressing xlEPOR-FDC/P2 cells and huEPO receptor-expressing UT-7/EPO cells, in a dose-dependent manner. 25898205 2 73 contain has 336:338 arg1 EPO 306:308 EPO 306:308 EPO in Xenopus laevis (xlEPO) 306:334 Intriguingly, we have previously found that EPO in Xenopus laevis (xlEPO) has no N-glycosylation sites, and cross-reacts with the human EPO (huEPO) receptor despite low homology with huEPO. 25898205 2 73 contain has 336:338 arg2 sites 359:363 no N-glycosylation sites 340:363 no N-glycosylation sites 340:363 Intriguingly, we have previously found that EPO in Xenopus laevis (xlEPO) has no N-glycosylation sites, and cross-reacts with the human EPO (huEPO) receptor despite low homology with huEPO. 25898205 6 74 theme huEPO 1016:1020 arg1 cells 1051:1055 huEPO receptor-expressing UT-7/EPO cells 1016:1055 huEPO receptor-expressing UT-7/EPO cells 1016:1055 All muteins stimulated the proliferation of both cell lines, xlEPO receptor-expressing xlEPOR-FDC/P2 cells and huEPO receptor-expressing UT-7/EPO cells, in a dose-dependent manner. 25898205 2 75 gly N-glycosylation 343:357 arg2 sites 359:363 no N-glycosylation sites 340:363 no N-glycosylation sites 340:363 Intriguingly, we have previously found that EPO in Xenopus laevis (xlEPO) has no N-glycosylation sites, and cross-reacts with the human EPO (huEPO) receptor despite low homology with huEPO. 25898205 0 76 dep in 70:71 arg1 vitro 73:77 vitro 73:77 vitro 73:77 The influence of artificially introduced N-glycosylation sites on the in vitro activity of Xenopus laevis erythropoietin. 25898205 6 77 theme cells 1006:1010 arg1 proliferation 932:944 the proliferation 928:944 the proliferation of both cell lines, xlEPO receptor-expressing xlEPOR-FDC/P2 cells and huEPO receptor-expressing UT-7/EPO cells 928:1055 All muteins stimulated the proliferation of both cell lines, xlEPO receptor-expressing xlEPOR-FDC/P2 cells and huEPO receptor-expressing UT-7/EPO cells, in a dose-dependent manner. 25898205 2 78 theme human 392:396 arg1 receptor 410:417 the human EPO (huEPO) receptor 388:417 the human EPO (huEPO) receptor 388:417 Intriguingly, we have previously found that EPO in Xenopus laevis (xlEPO) has no N-glycosylation sites, and cross-reacts with the human EPO (huEPO) receptor despite low homology with huEPO. 25898205 4 79 theme N-linked 695:702 arg1 carbohydrates 704:716 1-3 additional N-linked carbohydrates 680:716 1-3 additional N-linked carbohydrates 680:716 Seven xlEPO muteins, containing 1-3 additional N-linked carbohydrates at positions 24, 38, and/or 83, were expressed in COS-1 cells. 25898205 0 80 theme N-glycosylation 41:55 arg1 sites 57:61 artificially introduced N-glycosylation sites 17:61 artificially introduced N-glycosylation sites 17:61 The influence of artificially introduced N-glycosylation sites on the in vitro activity of Xenopus laevis erythropoietin. 25898205 9 81 theme N-glycosylation 1536:1550 arg1 sites 1552:1556 artificially introduced three N-glycosylation sites 1506:1556 artificially introduced three N-glycosylation sites 1506:1556 Hence, the EPO-EPOR binding site in X. laevis locates the distal region of artificially introduced three N-glycosylation sites, demonstrating that the vital conformation to exert biological activity is conserved between humans and X. laevis, despite the low similarity in primary structures of EPO and EPOR. 25898205 6 82 theme receptor-expressing 972:990 arg1 cells 1006:1010 xlEPO receptor-expressing xlEPOR-FDC/P2 cells 966:1010 xlEPO receptor-expressing xlEPOR-FDC/P2 cells 966:1010 All muteins stimulated the proliferation of both cell lines, xlEPO receptor-expressing xlEPOR-FDC/P2 cells and huEPO receptor-expressing UT-7/EPO cells, in a dose-dependent manner. 25898205 8 83 theme partial 1345:1351 arg1 muteins 1330:1336 the muteins 1326:1336 the muteins 1326:1336 The maximum effect on xlEPOR-FDC/P2 proliferation was decreased by the addition of N-linked carbohydrates, but that on UT-7/EPO proliferation was not changed, indicating that the muteins act as partial agonists to the xlEPO receptor, and near-full agonists to the huEPO receptor. 25898205 8 83 theme partial 1345:1351 arg1 agonists 1353:1360 partial agonists 1345:1360 partial agonists to the xlEPO receptor, and near-full agonists to the huEPO receptor 1345:1428 The maximum effect on xlEPOR-FDC/P2 proliferation was decreased by the addition of N-linked carbohydrates, but that on UT-7/EPO proliferation was not changed, indicating that the muteins act as partial agonists to the xlEPO receptor, and near-full agonists to the huEPO receptor. 25898205 3 84 from positions 531:539 arg1 xlEPO 518:522 wild-type xlEPO 508:522 wild-type xlEPO at the positions homologous to those in huEPO 508:568 In this study, we introduced N-glycosylation sites into wild-type xlEPO at the positions homologous to those in huEPO, and tested whether the glycosylated mutein retained its biological activity. 25898205 2 85 theme Xenopus 313:319 arg1 xlEPO 329:333 xlEPO 329:333 xlEPO 329:333 Intriguingly, we have previously found that EPO in Xenopus laevis (xlEPO) has no N-glycosylation sites, and cross-reacts with the human EPO (huEPO) receptor despite low homology with huEPO. 25898205 2 85 theme Xenopus 313:319 arg1 laevis 321:326 Xenopus laevis 313:326 Xenopus laevis (xlEPO) 313:334 Intriguingly, we have previously found that EPO in Xenopus laevis (xlEPO) has no N-glycosylation sites, and cross-reacts with the human EPO (huEPO) receptor despite low homology with huEPO. 25898205 8 86 link N-linked 1234:1241 arg1 carbohydrates 1243:1255 N-linked carbohydrates 1234:1255 N-linked carbohydrates 1234:1255 The maximum effect on xlEPOR-FDC/P2 proliferation was decreased by the addition of N-linked carbohydrates, but that on UT-7/EPO proliferation was not changed, indicating that the muteins act as partial agonists to the xlEPO receptor, and near-full agonists to the huEPO receptor. 25898205 3 87 theme glycosylated 594:605 arg1 mutein 607:612 the glycosylated mutein 590:612 the glycosylated mutein 590:612 In this study, we introduced N-glycosylation sites into wild-type xlEPO at the positions homologous to those in huEPO, and tested whether the glycosylated mutein retained its biological activity. 25898205 8 88 theme xlEPO 1369:1373 arg1 receptor 1375:1382 the xlEPO receptor, and near-full agonists 1365:1406 receptor 1375:1382 The maximum effect on xlEPOR-FDC/P2 proliferation was decreased by the addition of N-linked carbohydrates, but that on UT-7/EPO proliferation was not changed, indicating that the muteins act as partial agonists to the xlEPO receptor, and near-full agonists to the huEPO receptor. 25898205 9 89 theme vital 1582:1586 arg1 conformation 1588:1599 the vital conformation 1578:1599 the vital conformation to exert biological activity 1578:1628 Hence, the EPO-EPOR binding site in X. laevis locates the distal region of artificially introduced three N-glycosylation sites, demonstrating that the vital conformation to exert biological activity is conserved between humans and X. laevis, despite the low similarity in primary structures of EPO and EPOR. 27503338 5 0 theme intranasal 1485:1494 arg1 inoculation 1496:1506 intranasal inoculation 1485:1506 intranasal inoculation of mice 1485:1514 Furthermore, because the N residue at position 144 of HA was identified as the site of mismatch between the vaccine and epidemic strains of 2011-2012, we generated mutant viruses by reverse genetics and tested the functional importance of this particular NGS for antibody-mediated neutralization by intranasal inoculation of mice. 27503338 0 1 contain carrying 29:36 arg2 mutations 61:69 potential neutralizing mutations 38:69 potential neutralizing mutations 38:69 Re-emergence of H3N2 strains carrying potential neutralizing mutations at the N-linked glycosylation site at the hemagglutinin head, post the 2009 H1N1 pandemic. 27503338 0 1 contain carrying 29:36 arg1 Re-emergence 0:11 Re-emergence 0:11 Re-emergence of H3N2 strains carrying potential neutralizing mutations at the N-linked glycosylation site at the hemagglutinin head, post the 2009 H1N1 pandemic. 0:160 Re-emergence of H3N2 strains carrying potential neutralizing mutations at the N-linked glycosylation site at the hemagglutinin head, post the 2009 H1N1 pandemic. 27503338 7 2 theme HA 1714:1715 arg1 head 1726:1729 the HA globular head 1710:1729 the HA globular head 1710:1729 Our data suggest that the newly acquired NGSs in the HA globular head may play an important role in the re-emergence of endemic seasonal H3N2 strain by aiding the escape from humoral immunity. 27503338 5 3 theme epidemic 1306:1313 arg1 strains 1315:1321 the vaccine and epidemic strains 1290:1321 strains 1315:1321 Furthermore, because the N residue at position 144 of HA was identified as the site of mismatch between the vaccine and epidemic strains of 2011-2012, we generated mutant viruses by reverse genetics and tested the functional importance of this particular NGS for antibody-mediated neutralization by intranasal inoculation of mice. 27503338 1 4 gly glycosylation 322:334 arg2 N 312:312 N 312:312 N 312:312 Seasonally prevalent H1N1 and H3N2 influenza A viruses have evolved by antigenic drift; this evolution has resulted in the acquisition of asparagine (N)-linked glycosylation sites (NGSs) in the globular head of hemagglutinin (HA), thereby affecting the antigenic and receptor-binding properties, as well as virulence. 27503338 1 4 gly glycosylation 322:334 arg2 NGSs 343:346 NGSs 343:346 NGSs 343:346 Seasonally prevalent H1N1 and H3N2 influenza A viruses have evolved by antigenic drift; this evolution has resulted in the acquisition of asparagine (N)-linked glycosylation sites (NGSs) in the globular head of hemagglutinin (HA), thereby affecting the antigenic and receptor-binding properties, as well as virulence. 27503338 1 4 gly glycosylation 322:334 arg2 sites 336:340 asparagine (N)-linked glycosylation sites 300:340 asparagine (N)-linked glycosylation sites (NGSs) 300:347 Seasonally prevalent H1N1 and H3N2 influenza A viruses have evolved by antigenic drift; this evolution has resulted in the acquisition of asparagine (N)-linked glycosylation sites (NGSs) in the globular head of hemagglutinin (HA), thereby affecting the antigenic and receptor-binding properties, as well as virulence. 27503338 1 5 theme prevalent 173:181 arg1 H1N1 183:186 Seasonally prevalent H1N1 162:186 Seasonally prevalent H1N1 162:186 Seasonally prevalent H1N1 and H3N2 influenza A viruses have evolved by antigenic drift; this evolution has resulted in the acquisition of asparagine (N)-linked glycosylation sites (NGSs) in the globular head of hemagglutinin (HA), thereby affecting the antigenic and receptor-binding properties, as well as virulence. 27503338 4 6 theme amino 1053:1057 arg1 substitutions 1064:1076 amino acid substitutions 1053:1076 amino acid substitutions 1053:1076 To investigate whether these NGSs are associated with re-emergence of H3N2 within the subtype, we tested the effect of amino acid substitutions on neutralizing activity by using the antisera raised against H3N2 strains with or without additional NGSs. 27503338 4 7 from effect 1043:1048 arg1 activity 1094:1101 neutralizing activity 1081:1101 neutralizing activity 1081:1101 To investigate whether these NGSs are associated with re-emergence of H3N2 within the subtype, we tested the effect of amino acid substitutions on neutralizing activity by using the antisera raised against H3N2 strains with or without additional NGSs. 27503338 7 8 theme acquired 1693:1700 arg1 NGSs 1702:1705 the newly acquired NGSs 1683:1705 the newly acquired NGSs in the HA globular head 1683:1729 Our data suggest that the newly acquired NGSs in the HA globular head may play an important role in the re-emergence of endemic seasonal H3N2 strain by aiding the escape from humoral immunity. 27503338 1 9 theme influenza 197:205 arg1 viruses 209:215 H3N2 influenza A viruses 192:215 H3N2 influenza A viruses 192:215 Seasonally prevalent H1N1 and H3N2 influenza A viruses have evolved by antigenic drift; this evolution has resulted in the acquisition of asparagine (N)-linked glycosylation sites (NGSs) in the globular head of hemagglutinin (HA), thereby affecting the antigenic and receptor-binding properties, as well as virulence. 27503338 7 10 from immunity 1844:1851 arg1 escape 1824:1829 the escape 1820:1829 the escape from humoral immunity 1820:1851 Our data suggest that the newly acquired NGSs in the HA globular head may play an important role in the re-emergence of endemic seasonal H3N2 strain by aiding the escape from humoral immunity. 27503338 3 11 theme pandemic 733:740 arg1 H1N1pdm09 755:763 H1N1pdm09 755:763 H1N1pdm09 755:763 Interestingly, although the 2009 pandemic H1N1 strain (H1N1pdm09) lacks additional NGSs, clinically isolated H3N2 strains obtained during these seasons gained N (Asn) residues at positions 45 and 144 of HA that forms additional NGSs. 27503338 3 11 theme pandemic 733:740 arg1 strain 747:752 the 2009 pandemic H1N1 strain 724:752 the 2009 pandemic H1N1 strain (H1N1pdm09) 724:764 Interestingly, although the 2009 pandemic H1N1 strain (H1N1pdm09) lacks additional NGSs, clinically isolated H3N2 strains obtained during these seasons gained N (Asn) residues at positions 45 and 144 of HA that forms additional NGSs. 27503338 1 12 theme globular 356:363 arg1 head 365:368 the globular head 352:368 the globular head of hemagglutinin (HA) 352:390 Seasonally prevalent H1N1 and H3N2 influenza A viruses have evolved by antigenic drift; this evolution has resulted in the acquisition of asparagine (N)-linked glycosylation sites (NGSs) in the globular head of hemagglutinin (HA), thereby affecting the antigenic and receptor-binding properties, as well as virulence. 27503338 2 13 theme seasonal 546:553 arg1 strain 560:565 the traditional seasonal H1N1 strain 530:565 the traditional seasonal H1N1 strain 530:565 An epidemiological survey indicated that although the traditional seasonal H1N1 strain had disappeared, H3N2 became predominant again in the seasons (2010-11 and 2011-12) immediately following the H1N1 pandemic of 2009. 27503338 3 14 theme H3N2 809:812 arg1 strains 814:820 clinically isolated H3N2 strains 789:820 clinically isolated H3N2 strains obtained during these seasons 789:850 Interestingly, although the 2009 pandemic H1N1 strain (H1N1pdm09) lacks additional NGSs, clinically isolated H3N2 strains obtained during these seasons gained N (Asn) residues at positions 45 and 144 of HA that forms additional NGSs. 27503338 6 15 theme neutralization 1606:1619 arg1 activity 1621:1628 neutralization activity 1606:1628 neutralization activity 1606:1628 The results indicated that amino acid substitution at residue 144 significantly affected neutralization activity, acting as an escape mutation. 27503338 2 16 from seasons 621:627 arg1 predominant 596:606 predominant 596:606 predominant 596:606 An epidemiological survey indicated that although the traditional seasonal H1N1 strain had disappeared, H3N2 became predominant again in the seasons (2010-11 and 2011-12) immediately following the H1N1 pandemic of 2009. 27503338 4 17 theme substitutions 1064:1076 arg1 effect 1043:1048 the effect 1039:1048 the effect of amino acid substitutions on neutralizing activity 1039:1101 To investigate whether these NGSs are associated with re-emergence of H3N2 within the subtype, we tested the effect of amino acid substitutions on neutralizing activity by using the antisera raised against H3N2 strains with or without additional NGSs. 27503338 2 18 theme H1N1 677:680 arg1 pandemic 682:689 the H1N1 pandemic 673:689 the H1N1 pandemic of 2009 673:697 An epidemiological survey indicated that although the traditional seasonal H1N1 strain had disappeared, H3N2 became predominant again in the seasons (2010-11 and 2011-12) immediately following the H1N1 pandemic of 2009. 27503338 0 19 theme N-linked 78:85 arg1 site 101:104 the N-linked glycosylation site 74:104 the N-linked glycosylation site 74:104 Re-emergence of H3N2 strains carrying potential neutralizing mutations at the N-linked glycosylation site at the hemagglutinin head, post the 2009 H1N1 pandemic. 27503338 1 20 theme -linked 314:320 arg1 N 312:312 N 312:312 N 312:312 Seasonally prevalent H1N1 and H3N2 influenza A viruses have evolved by antigenic drift; this evolution has resulted in the acquisition of asparagine (N)-linked glycosylation sites (NGSs) in the globular head of hemagglutinin (HA), thereby affecting the antigenic and receptor-binding properties, as well as virulence. 27503338 1 20 theme -linked 314:320 arg1 NGSs 343:346 NGSs 343:346 NGSs 343:346 Seasonally prevalent H1N1 and H3N2 influenza A viruses have evolved by antigenic drift; this evolution has resulted in the acquisition of asparagine (N)-linked glycosylation sites (NGSs) in the globular head of hemagglutinin (HA), thereby affecting the antigenic and receptor-binding properties, as well as virulence. 27503338 1 20 theme -linked 314:320 arg1 sites 336:340 asparagine (N)-linked glycosylation sites 300:340 asparagine (N)-linked glycosylation sites (NGSs) 300:347 Seasonally prevalent H1N1 and H3N2 influenza A viruses have evolved by antigenic drift; this evolution has resulted in the acquisition of asparagine (N)-linked glycosylation sites (NGSs) in the globular head of hemagglutinin (HA), thereby affecting the antigenic and receptor-binding properties, as well as virulence. 27503338 2 21 dep seasons 621:627 arg1 2010-11 630:636 2010-11 630:636 2010-11 630:636 An epidemiological survey indicated that although the traditional seasonal H1N1 strain had disappeared, H3N2 became predominant again in the seasons (2010-11 and 2011-12) immediately following the H1N1 pandemic of 2009. 27503338 2 21 dep seasons 621:627 arg1 2011-12 642:648 2011-12 642:648 2011-12 642:648 An epidemiological survey indicated that although the traditional seasonal H1N1 strain had disappeared, H3N2 became predominant again in the seasons (2010-11 and 2011-12) immediately following the H1N1 pandemic of 2009. 27503338 1 22 theme sites 336:340 arg1 acquisition 285:295 the acquisition 281:295 the acquisition of asparagine (N)-linked glycosylation sites (NGSs) in the globular head of hemagglutinin (HA) 281:390 Seasonally prevalent H1N1 and H3N2 influenza A viruses have evolved by antigenic drift; this evolution has resulted in the acquisition of asparagine (N)-linked glycosylation sites (NGSs) in the globular head of hemagglutinin (HA), thereby affecting the antigenic and receptor-binding properties, as well as virulence. 27503338 6 23 theme acid 1550:1553 arg1 substitution 1555:1566 amino acid substitution 1544:1566 amino acid substitution at residue 144 1544:1581 The results indicated that amino acid substitution at residue 144 significantly affected neutralization activity, acting as an escape mutation. 27503338 0 24 gly glycosylation 87:99 arg2 head 127:130 the hemagglutinin head 109:130 the hemagglutinin head 109:130 Re-emergence of H3N2 strains carrying potential neutralizing mutations at the N-linked glycosylation site at the hemagglutinin head, post the 2009 H1N1 pandemic. 27503338 0 24 gly glycosylation 87:99 arg2 site 101:104 the N-linked glycosylation site 74:104 the N-linked glycosylation site 74:104 Re-emergence of H3N2 strains carrying potential neutralizing mutations at the N-linked glycosylation site at the hemagglutinin head, post the 2009 H1N1 pandemic. 27503338 6 25 theme escape 1644:1649 arg1 mutation 1651:1658 an escape mutation 1641:1658 an escape mutation 1641:1658 The results indicated that amino acid substitution at residue 144 significantly affected neutralization activity, acting as an escape mutation. 27503338 5 26 theme reverse 1368:1374 arg1 genetics 1376:1383 reverse genetics 1368:1383 reverse genetics 1368:1383 Furthermore, because the N residue at position 144 of HA was identified as the site of mismatch between the vaccine and epidemic strains of 2011-2012, we generated mutant viruses by reverse genetics and tested the functional importance of this particular NGS for antibody-mediated neutralization by intranasal inoculation of mice. 27503338 5 27 theme NGS 1441:1443 arg1 importance 1411:1420 the functional importance 1396:1420 the functional importance of this particular NGS for antibody-mediated neutralization 1396:1480 Furthermore, because the N residue at position 144 of HA was identified as the site of mismatch between the vaccine and epidemic strains of 2011-2012, we generated mutant viruses by reverse genetics and tested the functional importance of this particular NGS for antibody-mediated neutralization by intranasal inoculation of mice. 27503338 4 28 theme H3N2 1140:1143 arg1 strains 1145:1151 H3N2 strains 1140:1151 H3N2 strains with or without additional NGSs 1140:1183 To investigate whether these NGSs are associated with re-emergence of H3N2 within the subtype, we tested the effect of amino acid substitutions on neutralizing activity by using the antisera raised against H3N2 strains with or without additional NGSs. 27503338 0 29 theme H3N2 16:19 arg1 strains 21:27 H3N2 strains 16:27 H3N2 strains 16:27 Re-emergence of H3N2 strains carrying potential neutralizing mutations at the N-linked glycosylation site at the hemagglutinin head, post the 2009 H1N1 pandemic. 27503338 5 30 theme antibody-mediated 1449:1465 arg1 neutralization 1467:1480 antibody-mediated neutralization 1449:1480 antibody-mediated neutralization 1449:1480 Furthermore, because the N residue at position 144 of HA was identified as the site of mismatch between the vaccine and epidemic strains of 2011-2012, we generated mutant viruses by reverse genetics and tested the functional importance of this particular NGS for antibody-mediated neutralization by intranasal inoculation of mice. 27503338 3 31 from positions 879:887 arg1 residues 867:874 N (Asn) residues 859:874 N (Asn) residues at positions 45 and 144 of HA that forms additional NGSs 859:931 Interestingly, although the 2009 pandemic H1N1 strain (H1N1pdm09) lacks additional NGSs, clinically isolated H3N2 strains obtained during these seasons gained N (Asn) residues at positions 45 and 144 of HA that forms additional NGSs. 27503338 0 32 theme neutralizing 48:59 arg1 mutations 61:69 potential neutralizing mutations 38:69 potential neutralizing mutations 38:69 Re-emergence of H3N2 strains carrying potential neutralizing mutations at the N-linked glycosylation site at the hemagglutinin head, post the 2009 H1N1 pandemic. 27503338 1 33 theme asparagine 300:309 arg1 N 312:312 N 312:312 N 312:312 Seasonally prevalent H1N1 and H3N2 influenza A viruses have evolved by antigenic drift; this evolution has resulted in the acquisition of asparagine (N)-linked glycosylation sites (NGSs) in the globular head of hemagglutinin (HA), thereby affecting the antigenic and receptor-binding properties, as well as virulence. 27503338 1 33 theme asparagine 300:309 arg1 NGSs 343:346 NGSs 343:346 NGSs 343:346 Seasonally prevalent H1N1 and H3N2 influenza A viruses have evolved by antigenic drift; this evolution has resulted in the acquisition of asparagine (N)-linked glycosylation sites (NGSs) in the globular head of hemagglutinin (HA), thereby affecting the antigenic and receptor-binding properties, as well as virulence. 27503338 1 33 theme asparagine 300:309 arg1 sites 336:340 asparagine (N)-linked glycosylation sites 300:340 asparagine (N)-linked glycosylation sites (NGSs) 300:347 Seasonally prevalent H1N1 and H3N2 influenza A viruses have evolved by antigenic drift; this evolution has resulted in the acquisition of asparagine (N)-linked glycosylation sites (NGSs) in the globular head of hemagglutinin (HA), thereby affecting the antigenic and receptor-binding properties, as well as virulence. 27503338 7 34 theme H3N2 1798:1801 arg1 strain 1803:1808 endemic seasonal H3N2 strain 1781:1808 endemic seasonal H3N2 strain 1781:1808 Our data suggest that the newly acquired NGSs in the HA globular head may play an important role in the re-emergence of endemic seasonal H3N2 strain by aiding the escape from humoral immunity. 27503338 7 35 theme endemic 1781:1787 arg1 strain 1803:1808 endemic seasonal H3N2 strain 1781:1808 endemic seasonal H3N2 strain 1781:1808 Our data suggest that the newly acquired NGSs in the HA globular head may play an important role in the re-emergence of endemic seasonal H3N2 strain by aiding the escape from humoral immunity. 27503338 5 36 theme mice 1511:1514 arg1 inoculation 1496:1506 intranasal inoculation 1485:1506 intranasal inoculation of mice 1485:1514 Furthermore, because the N residue at position 144 of HA was identified as the site of mismatch between the vaccine and epidemic strains of 2011-2012, we generated mutant viruses by reverse genetics and tested the functional importance of this particular NGS for antibody-mediated neutralization by intranasal inoculation of mice. 27503338 3 37 theme HA 903:904 arg1 positions 879:887 positions 45 and 144 879:898 positions 879:887 Interestingly, although the 2009 pandemic H1N1 strain (H1N1pdm09) lacks additional NGSs, clinically isolated H3N2 strains obtained during these seasons gained N (Asn) residues at positions 45 and 144 of HA that forms additional NGSs. 27503338 0 38 from head 127:130 arg1 site 101:104 the N-linked glycosylation site 74:104 the N-linked glycosylation site 74:104 Re-emergence of H3N2 strains carrying potential neutralizing mutations at the N-linked glycosylation site at the hemagglutinin head, post the 2009 H1N1 pandemic. 27503338 5 39 theme mismatch 1273:1280 arg1 mismatch 1273:1280 mismatch 1273:1280 mismatch between the vaccine and epidemic strains of 2011-2012 1273:1334 Furthermore, because the N residue at position 144 of HA was identified as the site of mismatch between the vaccine and epidemic strains of 2011-2012, we generated mutant viruses by reverse genetics and tested the functional importance of this particular NGS for antibody-mediated neutralization by intranasal inoculation of mice. 27503338 5 39 theme mismatch 1273:1280 arg1 site 1265:1268 the site 1261:1268 the site of mismatch between the vaccine and epidemic strains of 2011-2012 1261:1334 Furthermore, because the N residue at position 144 of HA was identified as the site of mismatch between the vaccine and epidemic strains of 2011-2012, we generated mutant viruses by reverse genetics and tested the functional importance of this particular NGS for antibody-mediated neutralization by intranasal inoculation of mice. 27503338 5 39 theme mismatch 1273:1280 arg1 residue 1213:1219 the N residue 1207:1219 the N residue at position 144 of HA 1207:1241 Furthermore, because the N residue at position 144 of HA was identified as the site of mismatch between the vaccine and epidemic strains of 2011-2012, we generated mutant viruses by reverse genetics and tested the functional importance of this particular NGS for antibody-mediated neutralization by intranasal inoculation of mice. 27503338 7 40 theme globular 1717:1724 arg1 head 1726:1729 the HA globular head 1710:1729 the HA globular head 1710:1729 Our data suggest that the newly acquired NGSs in the HA globular head may play an important role in the re-emergence of endemic seasonal H3N2 strain by aiding the escape from humoral immunity. 27503338 1 41 from acquisition 285:295 arg1 head 365:368 the globular head 352:368 the globular head of hemagglutinin (HA) 352:390 Seasonally prevalent H1N1 and H3N2 influenza A viruses have evolved by antigenic drift; this evolution has resulted in the acquisition of asparagine (N)-linked glycosylation sites (NGSs) in the globular head of hemagglutinin (HA), thereby affecting the antigenic and receptor-binding properties, as well as virulence. 27503338 4 42 theme neutralizing 1081:1092 arg1 activity 1094:1101 neutralizing activity 1081:1101 neutralizing activity 1081:1101 To investigate whether these NGSs are associated with re-emergence of H3N2 within the subtype, we tested the effect of amino acid substitutions on neutralizing activity by using the antisera raised against H3N2 strains with or without additional NGSs. 27503338 2 43 theme H1N1 555:558 arg1 strain 560:565 the traditional seasonal H1N1 strain 530:565 the traditional seasonal H1N1 strain 530:565 An epidemiological survey indicated that although the traditional seasonal H1N1 strain had disappeared, H3N2 became predominant again in the seasons (2010-11 and 2011-12) immediately following the H1N1 pandemic of 2009. 27503338 5 44 theme mutant 1350:1355 arg1 viruses 1357:1363 mutant viruses 1350:1363 mutant viruses 1350:1363 Furthermore, because the N residue at position 144 of HA was identified as the site of mismatch between the vaccine and epidemic strains of 2011-2012, we generated mutant viruses by reverse genetics and tested the functional importance of this particular NGS for antibody-mediated neutralization by intranasal inoculation of mice. 27503338 1 45 theme Seasonally 162:171 arg1 H1N1 183:186 Seasonally prevalent H1N1 162:186 Seasonally prevalent H1N1 162:186 Seasonally prevalent H1N1 and H3N2 influenza A viruses have evolved by antigenic drift; this evolution has resulted in the acquisition of asparagine (N)-linked glycosylation sites (NGSs) in the globular head of hemagglutinin (HA), thereby affecting the antigenic and receptor-binding properties, as well as virulence. 27503338 4 46 theme acid 1059:1062 arg1 substitutions 1064:1076 amino acid substitutions 1053:1076 amino acid substitutions 1053:1076 To investigate whether these NGSs are associated with re-emergence of H3N2 within the subtype, we tested the effect of amino acid substitutions on neutralizing activity by using the antisera raised against H3N2 strains with or without additional NGSs. 27503338 1 47 theme antigenic 415:423 arg1 properties 446:455 the antigenic and receptor-binding properties 411:455 the antigenic and receptor-binding properties 411:455 Seasonally prevalent H1N1 and H3N2 influenza A viruses have evolved by antigenic drift; this evolution has resulted in the acquisition of asparagine (N)-linked glycosylation sites (NGSs) in the globular head of hemagglutinin (HA), thereby affecting the antigenic and receptor-binding properties, as well as virulence. 27503338 5 48 theme 2011-2012 1326:1334 arg1 strains 1315:1321 the vaccine and epidemic strains 1290:1321 strains 1315:1321 Furthermore, because the N residue at position 144 of HA was identified as the site of mismatch between the vaccine and epidemic strains of 2011-2012, we generated mutant viruses by reverse genetics and tested the functional importance of this particular NGS for antibody-mediated neutralization by intranasal inoculation of mice. 27503338 1 49 theme H3N2 192:195 arg1 viruses 209:215 H3N2 influenza A viruses 192:215 H3N2 influenza A viruses 192:215 Seasonally prevalent H1N1 and H3N2 influenza A viruses have evolved by antigenic drift; this evolution has resulted in the acquisition of asparagine (N)-linked glycosylation sites (NGSs) in the globular head of hemagglutinin (HA), thereby affecting the antigenic and receptor-binding properties, as well as virulence. 27503338 6 50 from residue 1571:1577 arg1 substitution 1555:1566 amino acid substitution 1544:1566 amino acid substitution at residue 144 1544:1581 The results indicated that amino acid substitution at residue 144 significantly affected neutralization activity, acting as an escape mutation. 27503338 1 51 theme A 207:207 arg1 viruses 209:215 H3N2 influenza A viruses 192:215 H3N2 influenza A viruses 192:215 Seasonally prevalent H1N1 and H3N2 influenza A viruses have evolved by antigenic drift; this evolution has resulted in the acquisition of asparagine (N)-linked glycosylation sites (NGSs) in the globular head of hemagglutinin (HA), thereby affecting the antigenic and receptor-binding properties, as well as virulence. 27503338 2 52 theme epidemiological 483:497 arg1 survey 499:504 An epidemiological survey 480:504 An epidemiological survey 480:504 An epidemiological survey indicated that although the traditional seasonal H1N1 strain had disappeared, H3N2 became predominant again in the seasons (2010-11 and 2011-12) immediately following the H1N1 pandemic of 2009. 27503338 3 53 theme H1N1 742:745 arg1 H1N1pdm09 755:763 H1N1pdm09 755:763 H1N1pdm09 755:763 Interestingly, although the 2009 pandemic H1N1 strain (H1N1pdm09) lacks additional NGSs, clinically isolated H3N2 strains obtained during these seasons gained N (Asn) residues at positions 45 and 144 of HA that forms additional NGSs. 27503338 3 53 theme H1N1 742:745 arg1 strain 747:752 the 2009 pandemic H1N1 strain 724:752 the 2009 pandemic H1N1 strain (H1N1pdm09) 724:764 Interestingly, although the 2009 pandemic H1N1 strain (H1N1pdm09) lacks additional NGSs, clinically isolated H3N2 strains obtained during these seasons gained N (Asn) residues at positions 45 and 144 of HA that forms additional NGSs. 27503338 0 54 theme H1N1 147:150 arg1 pandemic 152:159 the 2009 H1N1 pandemic 138:159 the 2009 H1N1 pandemic 138:159 Re-emergence of H3N2 strains carrying potential neutralizing mutations at the N-linked glycosylation site at the hemagglutinin head, post the 2009 H1N1 pandemic. 27503338 2 55 theme traditional 534:544 arg1 strain 560:565 the traditional seasonal H1N1 strain 530:565 the traditional seasonal H1N1 strain 530:565 An epidemiological survey indicated that although the traditional seasonal H1N1 strain had disappeared, H3N2 became predominant again in the seasons (2010-11 and 2011-12) immediately following the H1N1 pandemic of 2009. 27503338 5 56 from position 1224:1231 arg1 mismatch 1273:1280 mismatch 1273:1280 mismatch between the vaccine and epidemic strains of 2011-2012 1273:1334 Furthermore, because the N residue at position 144 of HA was identified as the site of mismatch between the vaccine and epidemic strains of 2011-2012, we generated mutant viruses by reverse genetics and tested the functional importance of this particular NGS for antibody-mediated neutralization by intranasal inoculation of mice. 27503338 5 56 from position 1224:1231 arg1 site 1265:1268 the site 1261:1268 the site of mismatch between the vaccine and epidemic strains of 2011-2012 1261:1334 Furthermore, because the N residue at position 144 of HA was identified as the site of mismatch between the vaccine and epidemic strains of 2011-2012, we generated mutant viruses by reverse genetics and tested the functional importance of this particular NGS for antibody-mediated neutralization by intranasal inoculation of mice. 27503338 5 56 from position 1224:1231 arg1 residue 1213:1219 the N residue 1207:1219 the N residue at position 144 of HA 1207:1241 Furthermore, because the N residue at position 144 of HA was identified as the site of mismatch between the vaccine and epidemic strains of 2011-2012, we generated mutant viruses by reverse genetics and tested the functional importance of this particular NGS for antibody-mediated neutralization by intranasal inoculation of mice. 27503338 1 57 theme receptor-binding 429:444 arg1 properties 446:455 the antigenic and receptor-binding properties 411:455 the antigenic and receptor-binding properties 411:455 Seasonally prevalent H1N1 and H3N2 influenza A viruses have evolved by antigenic drift; this evolution has resulted in the acquisition of asparagine (N)-linked glycosylation sites (NGSs) in the globular head of hemagglutinin (HA), thereby affecting the antigenic and receptor-binding properties, as well as virulence. 27503338 1 58 theme hemagglutinin 373:385 arg1 head 365:368 the globular head 352:368 the globular head of hemagglutinin (HA) 352:390 Seasonally prevalent H1N1 and H3N2 influenza A viruses have evolved by antigenic drift; this evolution has resulted in the acquisition of asparagine (N)-linked glycosylation sites (NGSs) in the globular head of hemagglutinin (HA), thereby affecting the antigenic and receptor-binding properties, as well as virulence. 27503338 2 59 theme 2009 694:697 arg1 pandemic 682:689 the H1N1 pandemic 673:689 the H1N1 pandemic of 2009 673:697 An epidemiological survey indicated that although the traditional seasonal H1N1 strain had disappeared, H3N2 became predominant again in the seasons (2010-11 and 2011-12) immediately following the H1N1 pandemic of 2009. 27503338 5 60 theme N 1211:1211 arg1 mismatch 1273:1280 mismatch 1273:1280 mismatch between the vaccine and epidemic strains of 2011-2012 1273:1334 Furthermore, because the N residue at position 144 of HA was identified as the site of mismatch between the vaccine and epidemic strains of 2011-2012, we generated mutant viruses by reverse genetics and tested the functional importance of this particular NGS for antibody-mediated neutralization by intranasal inoculation of mice. 27503338 5 60 theme N 1211:1211 arg1 site 1265:1268 the site 1261:1268 the site of mismatch between the vaccine and epidemic strains of 2011-2012 1261:1334 Furthermore, because the N residue at position 144 of HA was identified as the site of mismatch between the vaccine and epidemic strains of 2011-2012, we generated mutant viruses by reverse genetics and tested the functional importance of this particular NGS for antibody-mediated neutralization by intranasal inoculation of mice. 27503338 5 60 theme N 1211:1211 arg1 residue 1213:1219 the N residue 1207:1219 the N residue at position 144 of HA 1207:1241 Furthermore, because the N residue at position 144 of HA was identified as the site of mismatch between the vaccine and epidemic strains of 2011-2012, we generated mutant viruses by reverse genetics and tested the functional importance of this particular NGS for antibody-mediated neutralization by intranasal inoculation of mice. 27503338 3 61 theme isolated 800:807 arg1 strains 814:820 clinically isolated H3N2 strains 789:820 clinically isolated H3N2 strains obtained during these seasons 789:850 Interestingly, although the 2009 pandemic H1N1 strain (H1N1pdm09) lacks additional NGSs, clinically isolated H3N2 strains obtained during these seasons gained N (Asn) residues at positions 45 and 144 of HA that forms additional NGSs. 27503338 0 62 theme glycosylation 87:99 arg1 site 101:104 the N-linked glycosylation site 74:104 the N-linked glycosylation site 74:104 Re-emergence of H3N2 strains carrying potential neutralizing mutations at the N-linked glycosylation site at the hemagglutinin head, post the 2009 H1N1 pandemic. 27503338 1 63 theme glycosylation 322:334 arg1 N 312:312 N 312:312 N 312:312 Seasonally prevalent H1N1 and H3N2 influenza A viruses have evolved by antigenic drift; this evolution has resulted in the acquisition of asparagine (N)-linked glycosylation sites (NGSs) in the globular head of hemagglutinin (HA), thereby affecting the antigenic and receptor-binding properties, as well as virulence. 27503338 1 63 theme glycosylation 322:334 arg1 NGSs 343:346 NGSs 343:346 NGSs 343:346 Seasonally prevalent H1N1 and H3N2 influenza A viruses have evolved by antigenic drift; this evolution has resulted in the acquisition of asparagine (N)-linked glycosylation sites (NGSs) in the globular head of hemagglutinin (HA), thereby affecting the antigenic and receptor-binding properties, as well as virulence. 27503338 1 63 theme glycosylation 322:334 arg1 sites 336:340 asparagine (N)-linked glycosylation sites 300:340 asparagine (N)-linked glycosylation sites (NGSs) 300:347 Seasonally prevalent H1N1 and H3N2 influenza A viruses have evolved by antigenic drift; this evolution has resulted in the acquisition of asparagine (N)-linked glycosylation sites (NGSs) in the globular head of hemagglutinin (HA), thereby affecting the antigenic and receptor-binding properties, as well as virulence. 27503338 5 64 theme functional 1400:1409 arg1 importance 1411:1420 the functional importance 1396:1420 the functional importance of this particular NGS for antibody-mediated neutralization 1396:1480 Furthermore, because the N residue at position 144 of HA was identified as the site of mismatch between the vaccine and epidemic strains of 2011-2012, we generated mutant viruses by reverse genetics and tested the functional importance of this particular NGS for antibody-mediated neutralization by intranasal inoculation of mice. 27503338 4 65 theme additional 1169:1178 arg1 NGSs 1180:1183 additional NGSs 1169:1183 additional NGSs 1169:1183 To investigate whether these NGSs are associated with re-emergence of H3N2 within the subtype, we tested the effect of amino acid substitutions on neutralizing activity by using the antisera raised against H3N2 strains with or without additional NGSs. 27503338 5 66 theme HA 1240:1241 arg1 position 1224:1231 position 144 1224:1235 position 144 of HA 1224:1241 Furthermore, because the N residue at position 144 of HA was identified as the site of mismatch between the vaccine and epidemic strains of 2011-2012, we generated mutant viruses by reverse genetics and tested the functional importance of this particular NGS for antibody-mediated neutralization by intranasal inoculation of mice. 27503338 3 67 theme additional 772:781 arg1 NGSs 783:786 additional NGSs 772:786 additional NGSs 772:786 Interestingly, although the 2009 pandemic H1N1 strain (H1N1pdm09) lacks additional NGSs, clinically isolated H3N2 strains obtained during these seasons gained N (Asn) residues at positions 45 and 144 of HA that forms additional NGSs. 27503338 0 68 theme hemagglutinin 113:125 arg1 head 127:130 the hemagglutinin head 109:130 the hemagglutinin head 109:130 Re-emergence of H3N2 strains carrying potential neutralizing mutations at the N-linked glycosylation site at the hemagglutinin head, post the 2009 H1N1 pandemic. 27503338 7 69 theme humoral 1836:1842 arg1 immunity 1844:1851 humoral immunity 1836:1851 humoral immunity 1836:1851 Our data suggest that the newly acquired NGSs in the HA globular head may play an important role in the re-emergence of endemic seasonal H3N2 strain by aiding the escape from humoral immunity. 27503338 3 70 theme Asn 862:864 arg1 residues 867:874 N (Asn) residues 859:874 N (Asn) residues at positions 45 and 144 of HA that forms additional NGSs 859:931 Interestingly, although the 2009 pandemic H1N1 strain (H1N1pdm09) lacks additional NGSs, clinically isolated H3N2 strains obtained during these seasons gained N (Asn) residues at positions 45 and 144 of HA that forms additional NGSs. 27503338 6 71 theme amino 1544:1548 arg1 substitution 1555:1566 amino acid substitution 1544:1566 amino acid substitution at residue 144 1544:1581 The results indicated that amino acid substitution at residue 144 significantly affected neutralization activity, acting as an escape mutation. 27503338 3 72 theme N 859:859 arg1 residues 867:874 N (Asn) residues 859:874 N (Asn) residues at positions 45 and 144 of HA that forms additional NGSs 859:931 Interestingly, although the 2009 pandemic H1N1 strain (H1N1pdm09) lacks additional NGSs, clinically isolated H3N2 strains obtained during these seasons gained N (Asn) residues at positions 45 and 144 of HA that forms additional NGSs. 27503338 1 73 link -linked 314:320 arg1 N 312:312 N 312:312 N 312:312 Seasonally prevalent H1N1 and H3N2 influenza A viruses have evolved by antigenic drift; this evolution has resulted in the acquisition of asparagine (N)-linked glycosylation sites (NGSs) in the globular head of hemagglutinin (HA), thereby affecting the antigenic and receptor-binding properties, as well as virulence. 27503338 1 73 link -linked 314:320 arg1 NGSs 343:346 NGSs 343:346 NGSs 343:346 Seasonally prevalent H1N1 and H3N2 influenza A viruses have evolved by antigenic drift; this evolution has resulted in the acquisition of asparagine (N)-linked glycosylation sites (NGSs) in the globular head of hemagglutinin (HA), thereby affecting the antigenic and receptor-binding properties, as well as virulence. 27503338 1 73 link -linked 314:320 arg1 sites 336:340 asparagine (N)-linked glycosylation sites 300:340 asparagine (N)-linked glycosylation sites (NGSs) 300:347 Seasonally prevalent H1N1 and H3N2 influenza A viruses have evolved by antigenic drift; this evolution has resulted in the acquisition of asparagine (N)-linked glycosylation sites (NGSs) in the globular head of hemagglutinin (HA), thereby affecting the antigenic and receptor-binding properties, as well as virulence. 27503338 0 74 theme strains 21:27 arg1 Re-emergence 0:11 Re-emergence 0:11 Re-emergence of H3N2 strains carrying potential neutralizing mutations at the N-linked glycosylation site at the hemagglutinin head, post the 2009 H1N1 pandemic. 0:160 Re-emergence of H3N2 strains carrying potential neutralizing mutations at the N-linked glycosylation site at the hemagglutinin head, post the 2009 H1N1 pandemic. 27503338 3 75 theme additional 917:926 arg1 NGSs 928:931 additional NGSs 917:931 additional NGSs 917:931 Interestingly, although the 2009 pandemic H1N1 strain (H1N1pdm09) lacks additional NGSs, clinically isolated H3N2 strains obtained during these seasons gained N (Asn) residues at positions 45 and 144 of HA that forms additional NGSs. 27503338 0 76 theme potential 38:46 arg1 mutations 61:69 potential neutralizing mutations 38:69 potential neutralizing mutations 38:69 Re-emergence of H3N2 strains carrying potential neutralizing mutations at the N-linked glycosylation site at the hemagglutinin head, post the 2009 H1N1 pandemic. 27503338 7 77 theme strain 1803:1808 arg1 re-emergence 1765:1776 the re-emergence 1761:1776 the re-emergence of endemic seasonal H3N2 strain 1761:1808 Our data suggest that the newly acquired NGSs in the HA globular head may play an important role in the re-emergence of endemic seasonal H3N2 strain by aiding the escape from humoral immunity. 27503338 3 78 from 144 896:898 arg1 residues 867:874 N (Asn) residues 859:874 N (Asn) residues at positions 45 and 144 of HA that forms additional NGSs 859:931 Interestingly, although the 2009 pandemic H1N1 strain (H1N1pdm09) lacks additional NGSs, clinically isolated H3N2 strains obtained during these seasons gained N (Asn) residues at positions 45 and 144 of HA that forms additional NGSs. 27503338 7 79 theme seasonal 1789:1796 arg1 strain 1803:1808 endemic seasonal H3N2 strain 1781:1808 endemic seasonal H3N2 strain 1781:1808 Our data suggest that the newly acquired NGSs in the HA globular head may play an important role in the re-emergence of endemic seasonal H3N2 strain by aiding the escape from humoral immunity. 27503338 0 80 link N-linked 78:85 arg1 site 101:104 the N-linked glycosylation site 74:104 the N-linked glycosylation site 74:104 Re-emergence of H3N2 strains carrying potential neutralizing mutations at the N-linked glycosylation site at the hemagglutinin head, post the 2009 H1N1 pandemic. 27503338 2 81 from predominant 596:606 arg1 seasons 621:627 the seasons 617:627 the seasons (2010-11 and 2011-12) immediately following the H1N1 pandemic of 2009 617:697 An epidemiological survey indicated that although the traditional seasonal H1N1 strain had disappeared, H3N2 became predominant again in the seasons (2010-11 and 2011-12) immediately following the H1N1 pandemic of 2009. 27503338 5 82 theme vaccine 1294:1300 arg1 strains 1315:1321 the vaccine and epidemic strains 1290:1321 strains 1315:1321 Furthermore, because the N residue at position 144 of HA was identified as the site of mismatch between the vaccine and epidemic strains of 2011-2012, we generated mutant viruses by reverse genetics and tested the functional importance of this particular NGS for antibody-mediated neutralization by intranasal inoculation of mice. 27503338 7 83 from NGSs 1702:1705 arg1 head 1726:1729 the HA globular head 1710:1729 the HA globular head 1710:1729 Our data suggest that the newly acquired NGSs in the HA globular head may play an important role in the re-emergence of endemic seasonal H3N2 strain by aiding the escape from humoral immunity. 27503338 4 84 theme H3N2 1004:1007 arg1 re-emergence 988:999 re-emergence 988:999 re-emergence of H3N2 within the subtype 988:1026 To investigate whether these NGSs are associated with re-emergence of H3N2 within the subtype, we tested the effect of amino acid substitutions on neutralizing activity by using the antisera raised against H3N2 strains with or without additional NGSs. 27503338 5 85 theme particular 1430:1439 arg1 NGS 1441:1443 this particular NGS 1425:1443 this particular NGS 1425:1443 Furthermore, because the N residue at position 144 of HA was identified as the site of mismatch between the vaccine and epidemic strains of 2011-2012, we generated mutant viruses by reverse genetics and tested the functional importance of this particular NGS for antibody-mediated neutralization by intranasal inoculation of mice. 27503338 7 86 theme important 1743:1751 arg1 role 1753:1756 an important role 1740:1756 an important role 1740:1756 Our data suggest that the newly acquired NGSs in the HA globular head may play an important role in the re-emergence of endemic seasonal H3N2 strain by aiding the escape from humoral immunity. 27503338 1 87 theme antigenic 233:241 arg1 drift 243:247 antigenic drift 233:247 antigenic drift 233:247 Seasonally prevalent H1N1 and H3N2 influenza A viruses have evolved by antigenic drift; this evolution has resulted in the acquisition of asparagine (N)-linked glycosylation sites (NGSs) in the globular head of hemagglutinin (HA), thereby affecting the antigenic and receptor-binding properties, as well as virulence. 26742847 2 0 theme protein 354:360 arg1 biogenesis 362:371 protein biogenesis 354:371 protein biogenesis 354:371 Changes in channel function could result from variations in the protein biogenesis, stability, post-translational modification, and/or trafficking in any of the regulatory subunits forming cardiac L-type Ca(2+) channel complexes. 26742847 1 1 theme cardiac 269:275 arg1 arrhythmias 277:287 cardiac arrhythmias 269:287 cardiac arrhythmias 269:287 Alteration in the L-type current density is one aspect of the electrical remodeling observed in patients suffering from cardiac arrhythmias. 26742847 6 2 theme sites 881:885 arg1 mutation 859:866 the mutation 855:866 the mutation of only 6/16 sites 855:885 Nonetheless, the mutation of only 6/16 sites was sufficient to significantly 1) reduce the steady-state cell surface fluorescence of CaVα2δ1 as characterized by two-color flow cytometry assays and confocal imaging; 2) decrease protein stability estimated from cycloheximide chase assays; and 3) prevent the CaVα2δ1-mediated increase in the peak current density and voltage-dependent gating of CaV1.2. 26742847 6 2 theme sites 881:885 arg1 sufficient 891:900 sufficient 891:900 sufficient 891:900 Nonetheless, the mutation of only 6/16 sites was sufficient to significantly 1) reduce the steady-state cell surface fluorescence of CaVα2δ1 as characterized by two-color flow cytometry assays and confocal imaging; 2) decrease protein stability estimated from cycloheximide chase assays; and 3) prevent the CaVα2δ1-mediated increase in the peak current density and voltage-dependent gating of CaV1.2. 26742847 1 3 theme current 174:180 arg1 density 182:188 the L-type current density 163:188 the L-type current density 163:188 Alteration in the L-type current density is one aspect of the electrical remodeling observed in patients suffering from cardiac arrhythmias. 26742847 0 4 theme Cardiac 116:122 arg1 Activity 139:146 the Cardiac CaV1.2 Channel Activity 112:146 the Cardiac CaV1.2 Channel Activity 112:146 Identification of Glycosylation Sites Essential for Surface Expression of the CaVα2δ1 Subunit and Modulation of the Cardiac CaV1.2 Channel Activity. 26742847 2 5 theme channel 301:307 arg1 function 309:316 channel function 301:316 channel function 301:316 Changes in channel function could result from variations in the protein biogenesis, stability, post-translational modification, and/or trafficking in any of the regulatory subunits forming cardiac L-type Ca(2+) channel complexes. 26742847 9 6 gly N-glycosylation 1793:1807 arg1 CaVα2δ1 1812:1818 CaVα2δ1 1812:1818 CaVα2δ1 1812:1818 These results demonstrate that Asn-663 and to a lesser extent Asn-348, Asn-468, and Asn-812 contribute to protein stability/synthesis of CaVα2δ1, and furthermore that N-glycosylation of CaVα2δ1 is essential to produce functional L-type Ca(2+) channels. 26742847 5 7 theme sites 835:839 arg1 mutation 812:819 simultaneous mutation 799:819 simultaneous mutation of the 16 Asn sites 799:839 This change was also observed upon simultaneous mutation of the 16 Asn sites. 26742847 6 8 theme cell 946:949 arg1 fluorescence 959:970 the steady-state cell surface fluorescence 929:970 the steady-state cell surface fluorescence of CaVα2δ1 929:981 Nonetheless, the mutation of only 6/16 sites was sufficient to significantly 1) reduce the steady-state cell surface fluorescence of CaVα2δ1 as characterized by two-color flow cytometry assays and confocal imaging; 2) decrease protein stability estimated from cycloheximide chase assays; and 3) prevent the CaVα2δ1-mediated increase in the peak current density and voltage-dependent gating of CaV1.2. 26742847 9 9 theme CaVα2δ1 1763:1769 arg1 stability/synthesis 1740:1758 protein stability/synthesis 1732:1758 protein stability/synthesis of CaVα2δ1 1732:1769 These results demonstrate that Asn-663 and to a lesser extent Asn-348, Asn-468, and Asn-812 contribute to protein stability/synthesis of CaVα2δ1, and furthermore that N-glycosylation of CaVα2δ1 is essential to produce functional L-type Ca(2+) channels. 26742847 8 10 theme protein 1467:1473 arg1 stability/synthesis 1475:1493 protein stability/synthesis 1467:1493 protein stability/synthesis 1467:1493 Single mutation N663Q and double mutations N348Q/N468Q, N348Q/N812Q, and N468Q/N812Q decreased protein stability/synthesis and nearly abolished steady-state cell surface density of CaVα2δ1 as well as the CaVα2δ1-induced up-regulation of L-type currents. 26742847 6 11 theme CaV1.2 1235:1240 arg1 increase 1166:1173 the CaVα2δ1-mediated increase 1145:1173 the CaVα2δ1-mediated increase in the peak current density 1145:1201 Nonetheless, the mutation of only 6/16 sites was sufficient to significantly 1) reduce the steady-state cell surface fluorescence of CaVα2δ1 as characterized by two-color flow cytometry assays and confocal imaging; 2) decrease protein stability estimated from cycloheximide chase assays; and 3) prevent the CaVα2δ1-mediated increase in the peak current density and voltage-dependent gating of CaV1.2. 26742847 6 11 theme CaV1.2 1235:1240 arg1 gating 1225:1230 voltage-dependent gating 1207:1230 voltage-dependent gating of CaV1.2 1207:1240 Nonetheless, the mutation of only 6/16 sites was sufficient to significantly 1) reduce the steady-state cell surface fluorescence of CaVα2δ1 as characterized by two-color flow cytometry assays and confocal imaging; 2) decrease protein stability estimated from cycloheximide chase assays; and 3) prevent the CaVα2δ1-mediated increase in the peak current density and voltage-dependent gating of CaV1.2. 26742847 4 12 theme enzymatic 648:656 arg1 removal 658:664 enzymatic removal 648:664 enzymatic removal of N-glycans 648:677 Here, we show that enzymatic removal of N-glycans produced a 50-kDa shift in the mobility of cardiac and recombinant CaVα2δ1 proteins. 26742847 0 13 theme Channel 131:137 arg1 Activity 139:146 the Cardiac CaV1.2 Channel Activity 112:146 the Cardiac CaV1.2 Channel Activity 112:146 Identification of Glycosylation Sites Essential for Surface Expression of the CaVα2δ1 Subunit and Modulation of the Cardiac CaV1.2 Channel Activity. 26742847 3 14 theme channel 612:618 arg1 complex 620:626 the cardiac L-type CaV1.2 channel complex 586:626 the cardiac L-type CaV1.2 channel complex 586:626 CaVα2δ1 is potentially the most heavily N-glycosylated subunit in the cardiac L-type CaV1.2 channel complex. 26742847 3 15 theme L-type 598:603 arg1 channel 612:618 the cardiac L-type CaV1.2 channel 586:618 the cardiac L-type CaV1.2 channel complex 586:626 CaVα2δ1 is potentially the most heavily N-glycosylated subunit in the cardiac L-type CaV1.2 channel complex. 26742847 4 16 theme cardiac 722:728 arg1 mobility 710:717 the mobility 706:717 the mobility of cardiac and recombinant CaVα2δ1 proteins 706:761 Here, we show that enzymatic removal of N-glycans produced a 50-kDa shift in the mobility of cardiac and recombinant CaVα2δ1 proteins. 26742847 3 17 from subunit 575:581 arg1 complex 620:626 the cardiac L-type CaV1.2 channel complex 586:626 the cardiac L-type CaV1.2 channel complex 586:626 CaVα2δ1 is potentially the most heavily N-glycosylated subunit in the cardiac L-type CaV1.2 channel complex. 26742847 6 18 theme cytometry 1018:1026 arg1 assays 1028:1033 two-color flow cytometry assays 1003:1033 two-color flow cytometry assays 1003:1033 Nonetheless, the mutation of only 6/16 sites was sufficient to significantly 1) reduce the steady-state cell surface fluorescence of CaVα2δ1 as characterized by two-color flow cytometry assays and confocal imaging; 2) decrease protein stability estimated from cycloheximide chase assays; and 3) prevent the CaVα2δ1-mediated increase in the peak current density and voltage-dependent gating of CaV1.2. 26742847 2 19 theme channel 501:507 arg1 complexes 509:517 cardiac L-type Ca(2+) channel complexes 479:517 cardiac L-type Ca(2+) channel complexes 479:517 Changes in channel function could result from variations in the protein biogenesis, stability, post-translational modification, and/or trafficking in any of the regulatory subunits forming cardiac L-type Ca(2+) channel complexes. 26742847 8 20 theme cell 1529:1532 arg1 density 1542:1548 steady-state cell surface density 1516:1548 steady-state cell surface density of CaVα2δ1 as well as the CaVα2δ1-induced up-regulation of L-type currents 1516:1623 Single mutation N663Q and double mutations N348Q/N468Q, N348Q/N812Q, and N468Q/N812Q decreased protein stability/synthesis and nearly abolished steady-state cell surface density of CaVα2δ1 as well as the CaVα2δ1-induced up-regulation of L-type currents. 26742847 7 21 theme CaVα2δ1 1354:1360 arg1 function 1362:1369 CaVα2δ1 function 1354:1369 CaVα2δ1 function 1354:1369 Reversing the N348Q and N812Q mutations in the non-operational sextuplet Asn mutant protein partially restored CaVα2δ1 function. 26742847 4 22 theme 50-kDa 690:695 arg1 shift 697:701 a 50-kDa shift 688:701 a 50-kDa shift in the mobility of cardiac and recombinant CaVα2δ1 proteins 688:761 Here, we show that enzymatic removal of N-glycans produced a 50-kDa shift in the mobility of cardiac and recombinant CaVα2δ1 proteins. 26742847 6 23 theme two-color 1003:1011 arg1 assays 1028:1033 two-color flow cytometry assays 1003:1033 two-color flow cytometry assays 1003:1033 Nonetheless, the mutation of only 6/16 sites was sufficient to significantly 1) reduce the steady-state cell surface fluorescence of CaVα2δ1 as characterized by two-color flow cytometry assays and confocal imaging; 2) decrease protein stability estimated from cycloheximide chase assays; and 3) prevent the CaVα2δ1-mediated increase in the peak current density and voltage-dependent gating of CaV1.2. 26742847 0 24 theme CaVα2δ1 78:84 arg1 Subunit 86:92 the CaVα2δ1 Subunit 74:92 the CaVα2δ1 Subunit 74:92 Identification of Glycosylation Sites Essential for Surface Expression of the CaVα2δ1 Subunit and Modulation of the Cardiac CaV1.2 Channel Activity. 26742847 8 25 dep mutations 1405:1413 arg1 mutations 1405:1413 double mutations 1398:1413 double mutations N348Q/N468Q, N348Q/N812Q, and N468Q/N812Q 1398:1455 Single mutation N663Q and double mutations N348Q/N468Q, N348Q/N812Q, and N468Q/N812Q decreased protein stability/synthesis and nearly abolished steady-state cell surface density of CaVα2δ1 as well as the CaVα2δ1-induced up-regulation of L-type currents. 26742847 8 25 dep mutations 1405:1413 arg1 N348Q/N812Q 1428:1438 N348Q/N812Q 1428:1438 N348Q/N812Q 1428:1438 Single mutation N663Q and double mutations N348Q/N468Q, N348Q/N812Q, and N468Q/N812Q decreased protein stability/synthesis and nearly abolished steady-state cell surface density of CaVα2δ1 as well as the CaVα2δ1-induced up-regulation of L-type currents. 26742847 8 25 dep mutations 1405:1413 arg1 N468Q/N812Q 1445:1455 N468Q/N812Q 1445:1455 N468Q/N812Q 1445:1455 Single mutation N663Q and double mutations N348Q/N468Q, N348Q/N812Q, and N468Q/N812Q decreased protein stability/synthesis and nearly abolished steady-state cell surface density of CaVα2δ1 as well as the CaVα2δ1-induced up-regulation of L-type currents. 26742847 8 25 dep mutations 1405:1413 arg1 N348Q/N468Q 1415:1425 N348Q/N468Q 1415:1425 N348Q/N468Q 1415:1425 Single mutation N663Q and double mutations N348Q/N468Q, N348Q/N812Q, and N468Q/N812Q decreased protein stability/synthesis and nearly abolished steady-state cell surface density of CaVα2δ1 as well as the CaVα2δ1-induced up-regulation of L-type currents. 26742847 8 26 theme CaVα2δ1 1553:1559 arg1 density 1542:1548 steady-state cell surface density 1516:1548 steady-state cell surface density of CaVα2δ1 as well as the CaVα2δ1-induced up-regulation of L-type currents 1516:1623 Single mutation N663Q and double mutations N348Q/N468Q, N348Q/N812Q, and N468Q/N812Q decreased protein stability/synthesis and nearly abolished steady-state cell surface density of CaVα2δ1 as well as the CaVα2δ1-induced up-regulation of L-type currents. 26742847 8 26 theme CaVα2δ1 1553:1559 arg1 up-regulation 1592:1604 the CaVα2δ1-induced up-regulation 1572:1604 steady-state cell surface density of CaVα2δ1 as well as the CaVα2δ1-induced up-regulation of L-type currents 1516:1623 Single mutation N663Q and double mutations N348Q/N468Q, N348Q/N812Q, and N468Q/N812Q decreased protein stability/synthesis and nearly abolished steady-state cell surface density of CaVα2δ1 as well as the CaVα2δ1-induced up-regulation of L-type currents. 26742847 6 27 theme CaVα2δ1 975:981 arg1 fluorescence 959:970 the steady-state cell surface fluorescence 929:970 the steady-state cell surface fluorescence of CaVα2δ1 929:981 Nonetheless, the mutation of only 6/16 sites was sufficient to significantly 1) reduce the steady-state cell surface fluorescence of CaVα2δ1 as characterized by two-color flow cytometry assays and confocal imaging; 2) decrease protein stability estimated from cycloheximide chase assays; and 3) prevent the CaVα2δ1-mediated increase in the peak current density and voltage-dependent gating of CaV1.2. 26742847 9 28 theme functional 1844:1853 arg1 channels 1869:1876 functional L-type Ca(2+) channels 1844:1876 functional L-type Ca(2+) channels 1844:1876 These results demonstrate that Asn-663 and to a lesser extent Asn-348, Asn-468, and Asn-812 contribute to protein stability/synthesis of CaVα2δ1, and furthermore that N-glycosylation of CaVα2δ1 is essential to produce functional L-type Ca(2+) channels. 26742847 8 29 theme Single 1372:1377 arg1 N663Q 1388:1392 Single mutation N663Q 1372:1392 Single mutation N663Q 1372:1392 Single mutation N663Q and double mutations N348Q/N468Q, N348Q/N812Q, and N468Q/N812Q decreased protein stability/synthesis and nearly abolished steady-state cell surface density of CaVα2δ1 as well as the CaVα2δ1-induced up-regulation of L-type currents. 26742847 6 30 theme decrease 1060:1067 arg1 stability 1077:1085 decrease protein stability 1060:1085 decrease protein stability 1060:1085 Nonetheless, the mutation of only 6/16 sites was sufficient to significantly 1) reduce the steady-state cell surface fluorescence of CaVα2δ1 as characterized by two-color flow cytometry assays and confocal imaging; 2) decrease protein stability estimated from cycloheximide chase assays; and 3) prevent the CaVα2δ1-mediated increase in the peak current density and voltage-dependent gating of CaV1.2. 26742847 9 31 theme Ca 1862:1863 arg1 channels 1869:1876 functional L-type Ca(2+) channels 1844:1876 functional L-type Ca(2+) channels 1844:1876 These results demonstrate that Asn-663 and to a lesser extent Asn-348, Asn-468, and Asn-812 contribute to protein stability/synthesis of CaVα2δ1, and furthermore that N-glycosylation of CaVα2δ1 is essential to produce functional L-type Ca(2+) channels. 26742847 4 32 theme recombinant 734:744 arg1 proteins 754:761 recombinant CaVα2δ1 proteins 734:761 recombinant CaVα2δ1 proteins 734:761 Here, we show that enzymatic removal of N-glycans produced a 50-kDa shift in the mobility of cardiac and recombinant CaVα2δ1 proteins. 26742847 2 33 theme post-translational 385:402 arg1 modification 404:415 post-translational modification 385:415 post-translational modification 385:415 Changes in channel function could result from variations in the protein biogenesis, stability, post-translational modification, and/or trafficking in any of the regulatory subunits forming cardiac L-type Ca(2+) channel complexes. 26742847 9 34 theme 2+ 1865:1866 arg1 channels 1869:1876 functional L-type Ca(2+) channels 1844:1876 functional L-type Ca(2+) channels 1844:1876 These results demonstrate that Asn-663 and to a lesser extent Asn-348, Asn-468, and Asn-812 contribute to protein stability/synthesis of CaVα2δ1, and furthermore that N-glycosylation of CaVα2δ1 is essential to produce functional L-type Ca(2+) channels. 26742847 6 35 theme current 1187:1193 arg1 density 1195:1201 the peak current density 1178:1201 the peak current density 1178:1201 Nonetheless, the mutation of only 6/16 sites was sufficient to significantly 1) reduce the steady-state cell surface fluorescence of CaVα2δ1 as characterized by two-color flow cytometry assays and confocal imaging; 2) decrease protein stability estimated from cycloheximide chase assays; and 3) prevent the CaVα2δ1-mediated increase in the peak current density and voltage-dependent gating of CaV1.2. 26742847 4 36 theme proteins 754:761 arg1 mobility 710:717 the mobility 706:717 the mobility of cardiac and recombinant CaVα2δ1 proteins 706:761 Here, we show that enzymatic removal of N-glycans produced a 50-kDa shift in the mobility of cardiac and recombinant CaVα2δ1 proteins. 26742847 0 37 theme Glycosylation 18:30 arg1 Sites 32:36 Glycosylation Sites 18:36 Glycosylation Sites Essential for Surface Expression of the CaVα2δ1 Subunit and Modulation of the Cardiac CaV1.2 Channel Activity 18:146 Identification of Glycosylation Sites Essential for Surface Expression of the CaVα2δ1 Subunit and Modulation of the Cardiac CaV1.2 Channel Activity. 26742847 7 38 theme Asn 1316:1318 arg1 protein 1327:1333 the non-operational sextuplet Asn mutant protein 1286:1333 the non-operational sextuplet Asn mutant protein 1286:1333 Reversing the N348Q and N812Q mutations in the non-operational sextuplet Asn mutant protein partially restored CaVα2δ1 function. 26742847 2 39 theme Ca 494:495 arg1 complexes 509:517 cardiac L-type Ca(2+) channel complexes 479:517 cardiac L-type Ca(2+) channel complexes 479:517 Changes in channel function could result from variations in the protein biogenesis, stability, post-translational modification, and/or trafficking in any of the regulatory subunits forming cardiac L-type Ca(2+) channel complexes. 26742847 8 40 theme L-type 1609:1614 arg1 currents 1616:1623 L-type currents 1609:1623 L-type currents 1609:1623 Single mutation N663Q and double mutations N348Q/N468Q, N348Q/N812Q, and N468Q/N812Q decreased protein stability/synthesis and nearly abolished steady-state cell surface density of CaVα2δ1 as well as the CaVα2δ1-induced up-regulation of L-type currents. 26742847 0 41 theme Essential 38:46 arg1 Sites 32:36 Glycosylation Sites 18:36 Glycosylation Sites Essential for Surface Expression of the CaVα2δ1 Subunit and Modulation of the Cardiac CaV1.2 Channel Activity 18:146 Identification of Glycosylation Sites Essential for Surface Expression of the CaVα2δ1 Subunit and Modulation of the Cardiac CaV1.2 Channel Activity. 26742847 7 42 theme non-operational 1290:1304 arg1 protein 1327:1333 the non-operational sextuplet Asn mutant protein 1286:1333 the non-operational sextuplet Asn mutant protein 1286:1333 Reversing the N348Q and N812Q mutations in the non-operational sextuplet Asn mutant protein partially restored CaVα2δ1 function. 26742847 2 43 theme cardiac 479:485 arg1 complexes 509:517 cardiac L-type Ca(2+) channel complexes 479:517 cardiac L-type Ca(2+) channel complexes 479:517 Changes in channel function could result from variations in the protein biogenesis, stability, post-translational modification, and/or trafficking in any of the regulatory subunits forming cardiac L-type Ca(2+) channel complexes. 26742847 5 44 theme simultaneous 799:810 arg1 mutation 812:819 simultaneous mutation 799:819 simultaneous mutation of the 16 Asn sites 799:839 This change was also observed upon simultaneous mutation of the 16 Asn sites. 26742847 1 45 located observed 233:240 arg2 remodeling 222:231 the electrical remodeling 207:231 the electrical remodeling observed in patients suffering from cardiac arrhythmias 207:287 Alteration in the L-type current density is one aspect of the electrical remodeling observed in patients suffering from cardiac arrhythmias. 26742847 1 45 located observed 233:240 arg1 patients 245:252 patients 245:252 patients suffering from cardiac arrhythmias 245:287 Alteration in the L-type current density is one aspect of the electrical remodeling observed in patients suffering from cardiac arrhythmias. 26742847 1 46 theme electrical 211:220 arg1 remodeling 222:231 the electrical remodeling 207:231 the electrical remodeling observed in patients suffering from cardiac arrhythmias 207:287 Alteration in the L-type current density is one aspect of the electrical remodeling observed in patients suffering from cardiac arrhythmias. 26742847 9 47 theme lesser 1674:1679 arg1 extent 1681:1686 a lesser extent Asn-348 1672:1694 a lesser extent Asn-348 1672:1694 These results demonstrate that Asn-663 and to a lesser extent Asn-348, Asn-468, and Asn-812 contribute to protein stability/synthesis of CaVα2δ1, and furthermore that N-glycosylation of CaVα2δ1 is essential to produce functional L-type Ca(2+) channels. 26742847 7 48 theme N812Q 1267:1271 arg1 mutations 1273:1281 the N348Q and N812Q mutations 1253:1281 the N348Q and N812Q mutations in the non-operational sextuplet Asn mutant protein 1253:1333 Reversing the N348Q and N812Q mutations in the non-operational sextuplet Asn mutant protein partially restored CaVα2δ1 function. 26742847 8 49 theme double 1398:1403 arg1 mutations 1405:1413 double mutations 1398:1413 double mutations N348Q/N468Q, N348Q/N812Q, and N468Q/N812Q 1398:1455 Single mutation N663Q and double mutations N348Q/N468Q, N348Q/N812Q, and N468Q/N812Q decreased protein stability/synthesis and nearly abolished steady-state cell surface density of CaVα2δ1 as well as the CaVα2δ1-induced up-regulation of L-type currents. 26742847 8 49 theme double 1398:1403 arg1 N348Q/N812Q 1428:1438 N348Q/N812Q 1428:1438 N348Q/N812Q 1428:1438 Single mutation N663Q and double mutations N348Q/N468Q, N348Q/N812Q, and N468Q/N812Q decreased protein stability/synthesis and nearly abolished steady-state cell surface density of CaVα2δ1 as well as the CaVα2δ1-induced up-regulation of L-type currents. 26742847 8 49 theme double 1398:1403 arg1 N468Q/N812Q 1445:1455 N468Q/N812Q 1445:1455 N468Q/N812Q 1445:1455 Single mutation N663Q and double mutations N348Q/N468Q, N348Q/N812Q, and N468Q/N812Q decreased protein stability/synthesis and nearly abolished steady-state cell surface density of CaVα2δ1 as well as the CaVα2δ1-induced up-regulation of L-type currents. 26742847 8 49 theme double 1398:1403 arg1 N348Q/N468Q 1415:1425 N348Q/N468Q 1415:1425 N348Q/N468Q 1415:1425 Single mutation N663Q and double mutations N348Q/N468Q, N348Q/N812Q, and N468Q/N812Q decreased protein stability/synthesis and nearly abolished steady-state cell surface density of CaVα2δ1 as well as the CaVα2δ1-induced up-regulation of L-type currents. 26742847 7 50 theme N348Q 1257:1261 arg1 mutations 1273:1281 the N348Q and N812Q mutations 1253:1281 the N348Q and N812Q mutations in the non-operational sextuplet Asn mutant protein 1253:1333 Reversing the N348Q and N812Q mutations in the non-operational sextuplet Asn mutant protein partially restored CaVα2δ1 function. 26742847 4 51 from shift 697:701 arg1 mobility 710:717 the mobility 706:717 the mobility of cardiac and recombinant CaVα2δ1 proteins 706:761 Here, we show that enzymatic removal of N-glycans produced a 50-kDa shift in the mobility of cardiac and recombinant CaVα2δ1 proteins. 26742847 2 52 from variations 336:345 arg1 modification 404:415 post-translational modification 385:415 post-translational modification 385:415 Changes in channel function could result from variations in the protein biogenesis, stability, post-translational modification, and/or trafficking in any of the regulatory subunits forming cardiac L-type Ca(2+) channel complexes. 26742847 2 52 from variations 336:345 arg1 trafficking 425:435 trafficking 425:435 trafficking 425:435 Changes in channel function could result from variations in the protein biogenesis, stability, post-translational modification, and/or trafficking in any of the regulatory subunits forming cardiac L-type Ca(2+) channel complexes. 26742847 2 52 from variations 336:345 arg1 stability 374:382 stability 374:382 stability 374:382 Changes in channel function could result from variations in the protein biogenesis, stability, post-translational modification, and/or trafficking in any of the regulatory subunits forming cardiac L-type Ca(2+) channel complexes. 26742847 2 52 from variations 336:345 arg1 biogenesis 362:371 protein biogenesis 354:371 protein biogenesis 354:371 Changes in channel function could result from variations in the protein biogenesis, stability, post-translational modification, and/or trafficking in any of the regulatory subunits forming cardiac L-type Ca(2+) channel complexes. 26742847 1 53 theme L-type 167:172 arg1 density 182:188 the L-type current density 163:188 the L-type current density 163:188 Alteration in the L-type current density is one aspect of the electrical remodeling observed in patients suffering from cardiac arrhythmias. 26742847 0 54 theme Surface 52:58 arg1 Expression 60:69 Surface Expression 52:69 Surface Expression of the CaVα2δ1 Subunit 52:92 Identification of Glycosylation Sites Essential for Surface Expression of the CaVα2δ1 Subunit and Modulation of the Cardiac CaV1.2 Channel Activity. 26742847 2 55 from biogenesis 362:371 arg1 any 440:442 any 440:442 any 440:442 Changes in channel function could result from variations in the protein biogenesis, stability, post-translational modification, and/or trafficking in any of the regulatory subunits forming cardiac L-type Ca(2+) channel complexes. 26742847 6 56 theme CaVα2δ1-mediated 1149:1164 arg1 increase 1166:1173 the CaVα2δ1-mediated increase 1145:1173 the CaVα2δ1-mediated increase in the peak current density 1145:1201 Nonetheless, the mutation of only 6/16 sites was sufficient to significantly 1) reduce the steady-state cell surface fluorescence of CaVα2δ1 as characterized by two-color flow cytometry assays and confocal imaging; 2) decrease protein stability estimated from cycloheximide chase assays; and 3) prevent the CaVα2δ1-mediated increase in the peak current density and voltage-dependent gating of CaV1.2. 26742847 9 57 theme protein 1732:1738 arg1 stability/synthesis 1740:1758 protein stability/synthesis 1732:1758 protein stability/synthesis of CaVα2δ1 1732:1769 These results demonstrate that Asn-663 and to a lesser extent Asn-348, Asn-468, and Asn-812 contribute to protein stability/synthesis of CaVα2δ1, and furthermore that N-glycosylation of CaVα2δ1 is essential to produce functional L-type Ca(2+) channels. 26742847 7 58 from mutations 1273:1281 arg1 protein 1327:1333 the non-operational sextuplet Asn mutant protein 1286:1333 the non-operational sextuplet Asn mutant protein 1286:1333 Reversing the N348Q and N812Q mutations in the non-operational sextuplet Asn mutant protein partially restored CaVα2δ1 function. 26742847 4 59 theme N-glycans 669:677 arg1 removal 658:664 enzymatic removal 648:664 enzymatic removal of N-glycans 648:677 Here, we show that enzymatic removal of N-glycans produced a 50-kDa shift in the mobility of cardiac and recombinant CaVα2δ1 proteins. 26742847 0 60 theme CaV1.2 124:129 arg1 Activity 139:146 the Cardiac CaV1.2 Channel Activity 112:146 the Cardiac CaV1.2 Channel Activity 112:146 Identification of Glycosylation Sites Essential for Surface Expression of the CaVα2δ1 Subunit and Modulation of the Cardiac CaV1.2 Channel Activity. 26742847 3 61 theme N-glycosylated 560:573 arg1 subunit 575:581 the most heavily N-glycosylated subunit 543:581 the most heavily N-glycosylated subunit in the cardiac L-type CaV1.2 channel complex 543:626 CaVα2δ1 is potentially the most heavily N-glycosylated subunit in the cardiac L-type CaV1.2 channel complex. 26742847 3 61 theme N-glycosylated 560:573 arg1 CaVα2δ1 520:526 CaVα2δ1 520:526 CaVα2δ1 520:526 CaVα2δ1 is potentially the most heavily N-glycosylated subunit in the cardiac L-type CaV1.2 channel complex. 26742847 5 62 theme Asn 831:833 arg1 sites 835:839 the 16 Asn sites 824:839 the 16 Asn sites 824:839 This change was also observed upon simultaneous mutation of the 16 Asn sites. 26742847 6 63 theme surface 951:957 arg1 fluorescence 959:970 the steady-state cell surface fluorescence 929:970 the steady-state cell surface fluorescence of CaVα2δ1 929:981 Nonetheless, the mutation of only 6/16 sites was sufficient to significantly 1) reduce the steady-state cell surface fluorescence of CaVα2δ1 as characterized by two-color flow cytometry assays and confocal imaging; 2) decrease protein stability estimated from cycloheximide chase assays; and 3) prevent the CaVα2δ1-mediated increase in the peak current density and voltage-dependent gating of CaV1.2. 26742847 6 64 dep reduce 922:927 arg1 1 919:919 1 919:919 1 919:919 Nonetheless, the mutation of only 6/16 sites was sufficient to significantly 1) reduce the steady-state cell surface fluorescence of CaVα2δ1 as characterized by two-color flow cytometry assays and confocal imaging; 2) decrease protein stability estimated from cycloheximide chase assays; and 3) prevent the CaVα2δ1-mediated increase in the peak current density and voltage-dependent gating of CaV1.2. 26742847 0 65 theme Activity 139:146 arg1 Modulation 98:107 Modulation 98:107 Modulation of the Cardiac CaV1.2 Channel Activity 98:146 Identification of Glycosylation Sites Essential for Surface Expression of the CaVα2δ1 Subunit and Modulation of the Cardiac CaV1.2 Channel Activity. 26742847 0 65 theme Activity 139:146 arg1 Expression 60:69 Surface Expression 52:69 Surface Expression of the CaVα2δ1 Subunit 52:92 Identification of Glycosylation Sites Essential for Surface Expression of the CaVα2δ1 Subunit and Modulation of the Cardiac CaV1.2 Channel Activity. 26742847 3 66 theme CaV1.2 605:610 arg1 channel 612:618 the cardiac L-type CaV1.2 channel 586:618 the cardiac L-type CaV1.2 channel complex 586:626 CaVα2δ1 is potentially the most heavily N-glycosylated subunit in the cardiac L-type CaV1.2 channel complex. 26742847 6 67 dep prevent 1137:1143 arg1 3 1134:1134 3 1134:1134 3 1134:1134 Nonetheless, the mutation of only 6/16 sites was sufficient to significantly 1) reduce the steady-state cell surface fluorescence of CaVα2δ1 as characterized by two-color flow cytometry assays and confocal imaging; 2) decrease protein stability estimated from cycloheximide chase assays; and 3) prevent the CaVα2δ1-mediated increase in the peak current density and voltage-dependent gating of CaV1.2. 26742847 6 68 theme steady-state 933:944 arg1 fluorescence 959:970 the steady-state cell surface fluorescence 929:970 the steady-state cell surface fluorescence of CaVα2δ1 929:981 Nonetheless, the mutation of only 6/16 sites was sufficient to significantly 1) reduce the steady-state cell surface fluorescence of CaVα2δ1 as characterized by two-color flow cytometry assays and confocal imaging; 2) decrease protein stability estimated from cycloheximide chase assays; and 3) prevent the CaVα2δ1-mediated increase in the peak current density and voltage-dependent gating of CaV1.2. 26742847 3 69 theme cardiac 590:596 arg1 channel 612:618 the cardiac L-type CaV1.2 channel 586:618 the cardiac L-type CaV1.2 channel complex 586:626 CaVα2δ1 is potentially the most heavily N-glycosylated subunit in the cardiac L-type CaV1.2 channel complex. 26742847 6 70 dep characterized 986:998 arg1 estimated 1087:1095 estimated 1087:1095 estimated from cycloheximide chase assays 1087:1127 Nonetheless, the mutation of only 6/16 sites was sufficient to significantly 1) reduce the steady-state cell surface fluorescence of CaVα2δ1 as characterized by two-color flow cytometry assays and confocal imaging; 2) decrease protein stability estimated from cycloheximide chase assays; and 3) prevent the CaVα2δ1-mediated increase in the peak current density and voltage-dependent gating of CaV1.2. 26742847 6 70 dep characterized 986:998 arg1 2 1057:1057 2 1057:1057 2 1057:1057 Nonetheless, the mutation of only 6/16 sites was sufficient to significantly 1) reduce the steady-state cell surface fluorescence of CaVα2δ1 as characterized by two-color flow cytometry assays and confocal imaging; 2) decrease protein stability estimated from cycloheximide chase assays; and 3) prevent the CaVα2δ1-mediated increase in the peak current density and voltage-dependent gating of CaV1.2. 26742847 8 71 theme steady-state 1516:1527 arg1 density 1542:1548 steady-state cell surface density 1516:1548 steady-state cell surface density of CaVα2δ1 as well as the CaVα2δ1-induced up-regulation of L-type currents 1516:1623 Single mutation N663Q and double mutations N348Q/N468Q, N348Q/N812Q, and N468Q/N812Q decreased protein stability/synthesis and nearly abolished steady-state cell surface density of CaVα2δ1 as well as the CaVα2δ1-induced up-regulation of L-type currents. 26742847 6 72 theme voltage-dependent 1207:1223 arg1 gating 1225:1230 voltage-dependent gating 1207:1230 voltage-dependent gating of CaV1.2 1207:1240 Nonetheless, the mutation of only 6/16 sites was sufficient to significantly 1) reduce the steady-state cell surface fluorescence of CaVα2δ1 as characterized by two-color flow cytometry assays and confocal imaging; 2) decrease protein stability estimated from cycloheximide chase assays; and 3) prevent the CaVα2δ1-mediated increase in the peak current density and voltage-dependent gating of CaV1.2. 26742847 6 73 from gating 1225:1230 arg1 density 1195:1201 the peak current density 1178:1201 the peak current density 1178:1201 Nonetheless, the mutation of only 6/16 sites was sufficient to significantly 1) reduce the steady-state cell surface fluorescence of CaVα2δ1 as characterized by two-color flow cytometry assays and confocal imaging; 2) decrease protein stability estimated from cycloheximide chase assays; and 3) prevent the CaVα2δ1-mediated increase in the peak current density and voltage-dependent gating of CaV1.2. 26742847 8 74 theme surface 1534:1540 arg1 density 1542:1548 steady-state cell surface density 1516:1548 steady-state cell surface density of CaVα2δ1 as well as the CaVα2δ1-induced up-regulation of L-type currents 1516:1623 Single mutation N663Q and double mutations N348Q/N468Q, N348Q/N812Q, and N468Q/N812Q decreased protein stability/synthesis and nearly abolished steady-state cell surface density of CaVα2δ1 as well as the CaVα2δ1-induced up-regulation of L-type currents. 26742847 3 75 gly N-glycosylated 560:573 arg1 subunit 575:581 the most heavily N-glycosylated subunit 543:581 the most heavily N-glycosylated subunit in the cardiac L-type CaV1.2 channel complex 543:626 CaVα2δ1 is potentially the most heavily N-glycosylated subunit in the cardiac L-type CaV1.2 channel complex. 26742847 3 75 gly N-glycosylated 560:573 arg1 CaVα2δ1 520:526 CaVα2δ1 520:526 CaVα2δ1 520:526 CaVα2δ1 is potentially the most heavily N-glycosylated subunit in the cardiac L-type CaV1.2 channel complex. 26742847 2 76 from Changes 290:296 arg1 function 309:316 channel function 301:316 channel function 301:316 Changes in channel function could result from variations in the protein biogenesis, stability, post-translational modification, and/or trafficking in any of the regulatory subunits forming cardiac L-type Ca(2+) channel complexes. 26742847 6 77 theme flow 1013:1016 arg1 assays 1028:1033 two-color flow cytometry assays 1003:1033 two-color flow cytometry assays 1003:1033 Nonetheless, the mutation of only 6/16 sites was sufficient to significantly 1) reduce the steady-state cell surface fluorescence of CaVα2δ1 as characterized by two-color flow cytometry assays and confocal imaging; 2) decrease protein stability estimated from cycloheximide chase assays; and 3) prevent the CaVα2δ1-mediated increase in the peak current density and voltage-dependent gating of CaV1.2. 26742847 9 78 theme CaVα2δ1 1812:1818 arg1 N-glycosylation 1793:1807 N-glycosylation 1793:1807 N-glycosylation of CaVα2δ1 1793:1818 These results demonstrate that Asn-663 and to a lesser extent Asn-348, Asn-468, and Asn-812 contribute to protein stability/synthesis of CaVα2δ1, and furthermore that N-glycosylation of CaVα2δ1 is essential to produce functional L-type Ca(2+) channels. 26742847 6 79 theme peak 1182:1185 arg1 density 1195:1201 the peak current density 1178:1201 the peak current density 1178:1201 Nonetheless, the mutation of only 6/16 sites was sufficient to significantly 1) reduce the steady-state cell surface fluorescence of CaVα2δ1 as characterized by two-color flow cytometry assays and confocal imaging; 2) decrease protein stability estimated from cycloheximide chase assays; and 3) prevent the CaVα2δ1-mediated increase in the peak current density and voltage-dependent gating of CaV1.2. 26742847 0 80 theme Subunit 86:92 arg1 Modulation 98:107 Modulation 98:107 Modulation of the Cardiac CaV1.2 Channel Activity 98:146 Identification of Glycosylation Sites Essential for Surface Expression of the CaVα2δ1 Subunit and Modulation of the Cardiac CaV1.2 Channel Activity. 26742847 0 80 theme Subunit 86:92 arg1 Expression 60:69 Surface Expression 52:69 Surface Expression of the CaVα2δ1 Subunit 52:92 Identification of Glycosylation Sites Essential for Surface Expression of the CaVα2δ1 Subunit and Modulation of the Cardiac CaV1.2 Channel Activity. 26742847 6 81 from increase 1166:1173 arg1 density 1195:1201 the peak current density 1178:1201 the peak current density 1178:1201 Nonetheless, the mutation of only 6/16 sites was sufficient to significantly 1) reduce the steady-state cell surface fluorescence of CaVα2δ1 as characterized by two-color flow cytometry assays and confocal imaging; 2) decrease protein stability estimated from cycloheximide chase assays; and 3) prevent the CaVα2δ1-mediated increase in the peak current density and voltage-dependent gating of CaV1.2. 26742847 6 82 theme chase 1116:1120 arg1 assays 1122:1127 cycloheximide chase assays 1102:1127 cycloheximide chase assays 1102:1127 Nonetheless, the mutation of only 6/16 sites was sufficient to significantly 1) reduce the steady-state cell surface fluorescence of CaVα2δ1 as characterized by two-color flow cytometry assays and confocal imaging; 2) decrease protein stability estimated from cycloheximide chase assays; and 3) prevent the CaVα2δ1-mediated increase in the peak current density and voltage-dependent gating of CaV1.2. 26742847 1 83 from Alteration 149:158 arg1 density 182:188 the L-type current density 163:188 the L-type current density 163:188 Alteration in the L-type current density is one aspect of the electrical remodeling observed in patients suffering from cardiac arrhythmias. 26742847 6 84 theme protein 1069:1075 arg1 stability 1077:1085 decrease protein stability 1060:1085 decrease protein stability 1060:1085 Nonetheless, the mutation of only 6/16 sites was sufficient to significantly 1) reduce the steady-state cell surface fluorescence of CaVα2δ1 as characterized by two-color flow cytometry assays and confocal imaging; 2) decrease protein stability estimated from cycloheximide chase assays; and 3) prevent the CaVα2δ1-mediated increase in the peak current density and voltage-dependent gating of CaV1.2. 26742847 9 85 theme L-type 1855:1860 arg1 channels 1869:1876 functional L-type Ca(2+) channels 1844:1876 functional L-type Ca(2+) channels 1844:1876 These results demonstrate that Asn-663 and to a lesser extent Asn-348, Asn-468, and Asn-812 contribute to protein stability/synthesis of CaVα2δ1, and furthermore that N-glycosylation of CaVα2δ1 is essential to produce functional L-type Ca(2+) channels. 26742847 8 86 theme CaVα2δ1-induced 1576:1590 arg1 up-regulation 1592:1604 the CaVα2δ1-induced up-regulation 1572:1604 steady-state cell surface density of CaVα2δ1 as well as the CaVα2δ1-induced up-regulation of L-type currents 1516:1623 Single mutation N663Q and double mutations N348Q/N468Q, N348Q/N812Q, and N468Q/N812Q decreased protein stability/synthesis and nearly abolished steady-state cell surface density of CaVα2δ1 as well as the CaVα2δ1-induced up-regulation of L-type currents. 26742847 7 87 theme mutant 1320:1325 arg1 protein 1327:1333 the non-operational sextuplet Asn mutant protein 1286:1333 the non-operational sextuplet Asn mutant protein 1286:1333 Reversing the N348Q and N812Q mutations in the non-operational sextuplet Asn mutant protein partially restored CaVα2δ1 function. 26742847 2 88 theme regulatory 451:460 arg1 subunits 462:469 the regulatory subunits 447:469 the regulatory subunits forming cardiac L-type Ca(2+) channel complexes 447:517 Changes in channel function could result from variations in the protein biogenesis, stability, post-translational modification, and/or trafficking in any of the regulatory subunits forming cardiac L-type Ca(2+) channel complexes. 26742847 8 89 theme mutation 1379:1386 arg1 N663Q 1388:1392 Single mutation N663Q 1372:1392 Single mutation N663Q 1372:1392 Single mutation N663Q and double mutations N348Q/N468Q, N348Q/N812Q, and N468Q/N812Q decreased protein stability/synthesis and nearly abolished steady-state cell surface density of CaVα2δ1 as well as the CaVα2δ1-induced up-regulation of L-type currents. 26742847 0 90 theme Sites 32:36 arg1 Identification 0:13 Identification 0:13 Identification of Glycosylation Sites Essential for Surface Expression of the CaVα2δ1 Subunit and Modulation of the Cardiac CaV1.2 Channel Activity. 0:147 Identification of Glycosylation Sites Essential for Surface Expression of the CaVα2δ1 Subunit and Modulation of the Cardiac CaV1.2 Channel Activity. 26742847 7 91 theme sextuplet 1306:1314 arg1 protein 1327:1333 the non-operational sextuplet Asn mutant protein 1286:1333 the non-operational sextuplet Asn mutant protein 1286:1333 Reversing the N348Q and N812Q mutations in the non-operational sextuplet Asn mutant protein partially restored CaVα2δ1 function. 26742847 8 92 theme currents 1616:1623 arg1 density 1542:1548 steady-state cell surface density 1516:1548 steady-state cell surface density of CaVα2δ1 as well as the CaVα2δ1-induced up-regulation of L-type currents 1516:1623 Single mutation N663Q and double mutations N348Q/N468Q, N348Q/N812Q, and N468Q/N812Q decreased protein stability/synthesis and nearly abolished steady-state cell surface density of CaVα2δ1 as well as the CaVα2δ1-induced up-regulation of L-type currents. 26742847 8 92 theme currents 1616:1623 arg1 up-regulation 1592:1604 the CaVα2δ1-induced up-regulation 1572:1604 steady-state cell surface density of CaVα2δ1 as well as the CaVα2δ1-induced up-regulation of L-type currents 1516:1623 Single mutation N663Q and double mutations N348Q/N468Q, N348Q/N812Q, and N468Q/N812Q decreased protein stability/synthesis and nearly abolished steady-state cell surface density of CaVα2δ1 as well as the CaVα2δ1-induced up-regulation of L-type currents. 26742847 4 93 theme CaVα2δ1 746:752 arg1 proteins 754:761 recombinant CaVα2δ1 proteins 734:761 recombinant CaVα2δ1 proteins 734:761 Here, we show that enzymatic removal of N-glycans produced a 50-kDa shift in the mobility of cardiac and recombinant CaVα2δ1 proteins. 26742847 6 94 theme confocal 1039:1046 arg1 imaging 1048:1054 confocal imaging 1039:1054 confocal imaging 1039:1054 Nonetheless, the mutation of only 6/16 sites was sufficient to significantly 1) reduce the steady-state cell surface fluorescence of CaVα2δ1 as characterized by two-color flow cytometry assays and confocal imaging; 2) decrease protein stability estimated from cycloheximide chase assays; and 3) prevent the CaVα2δ1-mediated increase in the peak current density and voltage-dependent gating of CaV1.2. 26742847 2 95 theme L-type 487:492 arg1 2+ 497:498 2+ 497:498 2+ 497:498 Changes in channel function could result from variations in the protein biogenesis, stability, post-translational modification, and/or trafficking in any of the regulatory subunits forming cardiac L-type Ca(2+) channel complexes. 26742847 2 95 theme L-type 487:492 arg1 Ca 494:495 L-type Ca 487:495 cardiac L-type Ca(2+) channel complexes 479:517 Changes in channel function could result from variations in the protein biogenesis, stability, post-translational modification, and/or trafficking in any of the regulatory subunits forming cardiac L-type Ca(2+) channel complexes. 26742847 1 96 theme remodeling 222:231 arg1 aspect 197:202 one aspect 193:202 one aspect of the electrical remodeling observed in patients suffering from cardiac arrhythmias 193:287 Alteration in the L-type current density is one aspect of the electrical remodeling observed in patients suffering from cardiac arrhythmias. 26742847 6 97 theme cycloheximide 1102:1114 arg1 assays 1122:1127 cycloheximide chase assays 1102:1127 cycloheximide chase assays 1102:1127 Nonetheless, the mutation of only 6/16 sites was sufficient to significantly 1) reduce the steady-state cell surface fluorescence of CaVα2δ1 as characterized by two-color flow cytometry assays and confocal imaging; 2) decrease protein stability estimated from cycloheximide chase assays; and 3) prevent the CaVα2δ1-mediated increase in the peak current density and voltage-dependent gating of CaV1.2. 27681177 8 0 theme SLC26A6 1746:1752 arg1 function 1734:1741 oxalate transport function 1716:1741 oxalate transport function of SLC26A6 1716:1752 Taken together, these studies indicated that oxalate transport function of SLC26A6 is critically dependent on glycosylation and that exoglycosidase-mediated deglycosylation of SLC26A6 has the capacity to profoundly modulate SLC26A6 function. 27681177 4 1 theme human 758:762 arg1 SLC26A6 764:770 human SLC26A6 758:770 human SLC26A6 758:770 Through a series of enzymatic deglycosylation studies we confirmed that endogenously expressed mouse and human SLC26A6 are indeed glycosylated, that the oligosaccharides are principally attached via N-glycosidic linkage, and that there are tissue-specific differences in glycosylation. 27681177 3 2 theme proteins 533:540 arg1 variety 504:510 a wide variety 497:510 a wide variety of integral membrane proteins 497:540 N-linked glycosylation is known to critically affect folding, trafficking, and function in a wide variety of integral membrane proteins and could therefore potentially have a critical impact on SLC26A6 function and subsequent oxalate homeostasis. 27681177 3 2 theme proteins 533:540 arg1 proteins 533:540 integral membrane proteins 515:540 integral membrane proteins 515:540 N-linked glycosylation is known to critically affect folding, trafficking, and function in a wide variety of integral membrane proteins and could therefore potentially have a critical impact on SLC26A6 function and subsequent oxalate homeostasis. 27681177 7 3 theme plasma 1594:1599 arg1 membrane 1601:1608 the plasma membrane 1590:1608 the plasma membrane of intact cells 1590:1624 Functional studies of transfected SLC26A6 demonstrated that glycosylation at two sites in the putative second extracellular loop of SLC26A6 is critically important for chloride-dependent oxalate transport and that enzymatic deglycosylation of SLC26A6 expressed on the plasma membrane of intact cells strongly reduced oxalate transport activity. 27681177 8 4 gly deglycosylation 1828:1842 arg1 SLC26A6 1847:1853 SLC26A6 1847:1853 SLC26A6 1847:1853 Taken together, these studies indicated that oxalate transport function of SLC26A6 is critically dependent on glycosylation and that exoglycosidase-mediated deglycosylation of SLC26A6 has the capacity to profoundly modulate SLC26A6 function. 27681177 7 5 theme intact 1613:1618 arg1 cells 1620:1624 intact cells 1613:1624 intact cells 1613:1624 Functional studies of transfected SLC26A6 demonstrated that glycosylation at two sites in the putative second extracellular loop of SLC26A6 is critically important for chloride-dependent oxalate transport and that enzymatic deglycosylation of SLC26A6 expressed on the plasma membrane of intact cells strongly reduced oxalate transport activity. 27681177 5 6 dep In 939:940 arg1 vitro 942:946 vitro 942:946 vitro 942:946 In vitro cell culture experiments were then used to elucidate the functional significance of the addition of the carbohydrate moieties. 27681177 7 7 theme SLC26A6 1569:1575 arg1 deglycosylation 1550:1564 enzymatic deglycosylation 1540:1564 enzymatic deglycosylation of SLC26A6 expressed on the plasma membrane of intact cells 1540:1624 Functional studies of transfected SLC26A6 demonstrated that glycosylation at two sites in the putative second extracellular loop of SLC26A6 is critically important for chloride-dependent oxalate transport and that enzymatic deglycosylation of SLC26A6 expressed on the plasma membrane of intact cells strongly reduced oxalate transport activity. 27681177 5 8 theme addition 1036:1043 arg1 significance 1016:1027 the functional significance 1001:1027 the functional significance of the addition of the carbohydrate moieties 1001:1072 In vitro cell culture experiments were then used to elucidate the functional significance of the addition of the carbohydrate moieties. 27681177 1 9 theme hyperoxaluria 274:286 arg1 maintenance 217:227 the maintenance 213:227 the maintenance of oxalate homeostasis 213:250 The brush border Cl--oxalate exchanger SLC26A6 plays an essential role in mediating intestinal secretion of oxalate and is crucial for the maintenance of oxalate homeostasis and the prevention of hyperoxaluria and calcium oxalate nephrolithiasis. 27681177 1 9 theme hyperoxaluria 274:286 arg1 prevention 260:269 the prevention 256:269 the prevention of hyperoxaluria and calcium oxalate nephrolithiasis 256:322 The brush border Cl--oxalate exchanger SLC26A6 plays an essential role in mediating intestinal secretion of oxalate and is crucial for the maintenance of oxalate homeostasis and the prevention of hyperoxaluria and calcium oxalate nephrolithiasis. 27681177 3 10 theme SLC26A6 600:606 arg1 function 608:615 SLC26A6 function 600:615 SLC26A6 function 600:615 N-linked glycosylation is known to critically affect folding, trafficking, and function in a wide variety of integral membrane proteins and could therefore potentially have a critical impact on SLC26A6 function and subsequent oxalate homeostasis. 27681177 6 11 gly glycosylation 1145:1157 arg1 SLC26A6 1205:1211 SLC26A6 1205:1211 SLC26A6 1205:1211 Biotinylation studies of SLC26A6 glycosylation mutants indicated that glycosylation is not essential for cell surface delivery of SLC26A6 but suggested that it may affect the efficacy with which it is trafficked and maintained in the plasma membrane. 27681177 6 11 gly glycosylation 1145:1157 arg1 cell 1180:1183 cell surface delivery 1180:1200 cell surface delivery of SLC26A6 1180:1211 Biotinylation studies of SLC26A6 glycosylation mutants indicated that glycosylation is not essential for cell surface delivery of SLC26A6 but suggested that it may affect the efficacy with which it is trafficked and maintained in the plasma membrane. 27681177 6 11 gly glycosylation 1145:1157 arg1 surface 1185:1191 cell surface delivery 1180:1200 cell surface delivery of SLC26A6 1180:1211 Biotinylation studies of SLC26A6 glycosylation mutants indicated that glycosylation is not essential for cell surface delivery of SLC26A6 but suggested that it may affect the efficacy with which it is trafficked and maintained in the plasma membrane. 27681177 8 12 contain has 1855:1857 arg2 capacity 1863:1870 the capacity to profoundly modulate SLC26A6 function 1859:1910 the capacity to profoundly modulate SLC26A6 function 1859:1910 Taken together, these studies indicated that oxalate transport function of SLC26A6 is critically dependent on glycosylation and that exoglycosidase-mediated deglycosylation of SLC26A6 has the capacity to profoundly modulate SLC26A6 function. 27681177 8 12 contain has 1855:1857 arg1 deglycosylation 1828:1842 exoglycosidase-mediated deglycosylation 1804:1842 exoglycosidase-mediated deglycosylation of SLC26A6 1804:1853 Taken together, these studies indicated that oxalate transport function of SLC26A6 is critically dependent on glycosylation and that exoglycosidase-mediated deglycosylation of SLC26A6 has the capacity to profoundly modulate SLC26A6 function. 27681177 3 13 theme critical 581:588 arg1 impact 590:595 a critical impact 579:595 a critical impact 579:595 N-linked glycosylation is known to critically affect folding, trafficking, and function in a wide variety of integral membrane proteins and could therefore potentially have a critical impact on SLC26A6 function and subsequent oxalate homeostasis. 27681177 5 14 theme functional 1005:1014 arg1 significance 1016:1027 the functional significance 1001:1027 the functional significance of the addition of the carbohydrate moieties 1001:1072 In vitro cell culture experiments were then used to elucidate the functional significance of the addition of the carbohydrate moieties. 27681177 3 15 theme integral 515:522 arg1 proteins 533:540 integral membrane proteins 515:540 integral membrane proteins 515:540 N-linked glycosylation is known to critically affect folding, trafficking, and function in a wide variety of integral membrane proteins and could therefore potentially have a critical impact on SLC26A6 function and subsequent oxalate homeostasis. 27681177 6 16 theme surface 1185:1191 arg1 delivery 1193:1200 cell surface delivery 1180:1200 cell surface delivery of SLC26A6 1180:1211 Biotinylation studies of SLC26A6 glycosylation mutants indicated that glycosylation is not essential for cell surface delivery of SLC26A6 but suggested that it may affect the efficacy with which it is trafficked and maintained in the plasma membrane. 27681177 1 17 theme brush 82:86 arg1 border 88:93 The brush border 78:93 The brush border Cl--oxalate exchanger SLC26A6 78:123 The brush border Cl--oxalate exchanger SLC26A6 plays an essential role in mediating intestinal secretion of oxalate and is crucial for the maintenance of oxalate homeostasis and the prevention of hyperoxaluria and calcium oxalate nephrolithiasis. 27681177 7 18 theme putative 1420:1427 arg1 loop 1450:1453 the putative second extracellular loop 1416:1453 the putative second extracellular loop of SLC26A6 1416:1464 Functional studies of transfected SLC26A6 demonstrated that glycosylation at two sites in the putative second extracellular loop of SLC26A6 is critically important for chloride-dependent oxalate transport and that enzymatic deglycosylation of SLC26A6 expressed on the plasma membrane of intact cells strongly reduced oxalate transport activity. 27681177 1 19 theme oxalate 186:192 arg1 secretion 173:181 intestinal secretion 162:181 intestinal secretion of oxalate 162:192 The brush border Cl--oxalate exchanger SLC26A6 plays an essential role in mediating intestinal secretion of oxalate and is crucial for the maintenance of oxalate homeostasis and the prevention of hyperoxaluria and calcium oxalate nephrolithiasis. 27681177 7 20 gly deglycosylation 1550:1564 arg1 SLC26A6 1569:1575 SLC26A6 1569:1575 SLC26A6 expressed on the plasma membrane of intact cells 1569:1624 Functional studies of transfected SLC26A6 demonstrated that glycosylation at two sites in the putative second extracellular loop of SLC26A6 is critically important for chloride-dependent oxalate transport and that enzymatic deglycosylation of SLC26A6 expressed on the plasma membrane of intact cells strongly reduced oxalate transport activity. 27681177 1 21 theme border 88:93 arg1 SLC26A6 117:123 The brush border Cl--oxalate exchanger SLC26A6 78:123 The brush border Cl--oxalate exchanger SLC26A6 78:123 The brush border Cl--oxalate exchanger SLC26A6 plays an essential role in mediating intestinal secretion of oxalate and is crucial for the maintenance of oxalate homeostasis and the prevention of hyperoxaluria and calcium oxalate nephrolithiasis. 27681177 8 22 theme transport 1724:1732 arg1 function 1734:1741 oxalate transport function 1716:1741 oxalate transport function of SLC26A6 1716:1752 Taken together, these studies indicated that oxalate transport function of SLC26A6 is critically dependent on glycosylation and that exoglycosidase-mediated deglycosylation of SLC26A6 has the capacity to profoundly modulate SLC26A6 function. 27681177 6 23 theme cell 1180:1183 arg1 delivery 1193:1200 cell surface delivery 1180:1200 cell surface delivery of SLC26A6 1180:1211 Biotinylation studies of SLC26A6 glycosylation mutants indicated that glycosylation is not essential for cell surface delivery of SLC26A6 but suggested that it may affect the efficacy with which it is trafficked and maintained in the plasma membrane. 27681177 7 24 theme chloride-dependent 1494:1511 arg1 transport 1521:1529 chloride-dependent oxalate transport 1494:1529 chloride-dependent oxalate transport 1494:1529 Functional studies of transfected SLC26A6 demonstrated that glycosylation at two sites in the putative second extracellular loop of SLC26A6 is critically important for chloride-dependent oxalate transport and that enzymatic deglycosylation of SLC26A6 expressed on the plasma membrane of intact cells strongly reduced oxalate transport activity. 27681177 4 25 from differences 909:919 arg1 glycosylation 924:936 glycosylation 924:936 glycosylation 924:936 Through a series of enzymatic deglycosylation studies we confirmed that endogenously expressed mouse and human SLC26A6 are indeed glycosylated, that the oligosaccharides are principally attached via N-glycosidic linkage, and that there are tissue-specific differences in glycosylation. 27681177 1 26 theme Cl--oxalate 95:105 arg1 SLC26A6 117:123 The brush border Cl--oxalate exchanger SLC26A6 78:123 The brush border Cl--oxalate exchanger SLC26A6 78:123 The brush border Cl--oxalate exchanger SLC26A6 plays an essential role in mediating intestinal secretion of oxalate and is crucial for the maintenance of oxalate homeostasis and the prevention of hyperoxaluria and calcium oxalate nephrolithiasis. 27681177 8 27 theme SLC26A6 1895:1901 arg1 function 1903:1910 SLC26A6 function 1895:1910 SLC26A6 function 1895:1910 Taken together, these studies indicated that oxalate transport function of SLC26A6 is critically dependent on glycosylation and that exoglycosidase-mediated deglycosylation of SLC26A6 has the capacity to profoundly modulate SLC26A6 function. 27681177 5 28 theme cell 948:951 arg1 experiments 961:971 In vitro cell culture experiments 939:971 In vitro cell culture experiments 939:971 In vitro cell culture experiments were then used to elucidate the functional significance of the addition of the carbohydrate moieties. 27681177 1 29 theme calcium 292:298 arg1 nephrolithiasis 308:322 calcium oxalate nephrolithiasis 292:322 calcium oxalate nephrolithiasis 292:322 The brush border Cl--oxalate exchanger SLC26A6 plays an essential role in mediating intestinal secretion of oxalate and is crucial for the maintenance of oxalate homeostasis and the prevention of hyperoxaluria and calcium oxalate nephrolithiasis. 27681177 7 30 theme oxalate 1643:1649 arg1 activity 1661:1668 oxalate transport activity 1643:1668 oxalate transport activity 1643:1668 Functional studies of transfected SLC26A6 demonstrated that glycosylation at two sites in the putative second extracellular loop of SLC26A6 is critically important for chloride-dependent oxalate transport and that enzymatic deglycosylation of SLC26A6 expressed on the plasma membrane of intact cells strongly reduced oxalate transport activity. 27681177 1 31 theme exchanger 107:115 arg1 SLC26A6 117:123 The brush border Cl--oxalate exchanger SLC26A6 78:123 The brush border Cl--oxalate exchanger SLC26A6 78:123 The brush border Cl--oxalate exchanger SLC26A6 plays an essential role in mediating intestinal secretion of oxalate and is crucial for the maintenance of oxalate homeostasis and the prevention of hyperoxaluria and calcium oxalate nephrolithiasis. 27681177 5 32 theme culture 953:959 arg1 experiments 961:971 In vitro cell culture experiments 939:971 In vitro cell culture experiments 939:971 In vitro cell culture experiments were then used to elucidate the functional significance of the addition of the carbohydrate moieties. 27681177 3 33 theme N-linked 406:413 arg1 glycosylation 415:427 N-linked glycosylation 406:427 N-linked glycosylation 406:427 N-linked glycosylation is known to critically affect folding, trafficking, and function in a wide variety of integral membrane proteins and could therefore potentially have a critical impact on SLC26A6 function and subsequent oxalate homeostasis. 27681177 1 34 theme oxalate 300:306 arg1 nephrolithiasis 308:322 calcium oxalate nephrolithiasis 292:322 calcium oxalate nephrolithiasis 292:322 The brush border Cl--oxalate exchanger SLC26A6 plays an essential role in mediating intestinal secretion of oxalate and is crucial for the maintenance of oxalate homeostasis and the prevention of hyperoxaluria and calcium oxalate nephrolithiasis. 27681177 2 35 gly N-glycosylated 390:403 arg1 SLC26A6 371:377 SLC26A6 371:377 SLC26A6 371:377 Previous in vitro studies have suggested that SLC26A6 is heavily N-glycosylated. 27681177 6 36 theme plasma 1309:1314 arg1 membrane 1316:1323 the plasma membrane 1305:1323 the plasma membrane 1305:1323 Biotinylation studies of SLC26A6 glycosylation mutants indicated that glycosylation is not essential for cell surface delivery of SLC26A6 but suggested that it may affect the efficacy with which it is trafficked and maintained in the plasma membrane. 27681177 2 37 theme in 334:335 arg1 studies 343:349 Previous in vitro studies 325:349 Previous in vitro studies 325:349 Previous in vitro studies have suggested that SLC26A6 is heavily N-glycosylated. 27681177 5 38 used used 983:986 arg2 experiments 961:971 In vitro cell culture experiments 939:971 In vitro cell culture experiments 939:971 In vitro cell culture experiments were then used to elucidate the functional significance of the addition of the carbohydrate moieties. 27681177 4 39 theme enzymatic 673:681 arg1 studies 699:705 enzymatic deglycosylation studies 673:705 enzymatic deglycosylation studies 673:705 Through a series of enzymatic deglycosylation studies we confirmed that endogenously expressed mouse and human SLC26A6 are indeed glycosylated, that the oligosaccharides are principally attached via N-glycosidic linkage, and that there are tissue-specific differences in glycosylation. 27681177 7 40 theme enzymatic 1540:1548 arg1 deglycosylation 1550:1564 enzymatic deglycosylation 1540:1564 enzymatic deglycosylation of SLC26A6 expressed on the plasma membrane of intact cells 1540:1624 Functional studies of transfected SLC26A6 demonstrated that glycosylation at two sites in the putative second extracellular loop of SLC26A6 is critically important for chloride-dependent oxalate transport and that enzymatic deglycosylation of SLC26A6 expressed on the plasma membrane of intact cells strongly reduced oxalate transport activity. 27681177 1 41 theme nephrolithiasis 308:322 arg1 maintenance 217:227 the maintenance 213:227 the maintenance of oxalate homeostasis 213:250 The brush border Cl--oxalate exchanger SLC26A6 plays an essential role in mediating intestinal secretion of oxalate and is crucial for the maintenance of oxalate homeostasis and the prevention of hyperoxaluria and calcium oxalate nephrolithiasis. 27681177 1 41 theme nephrolithiasis 308:322 arg1 prevention 260:269 the prevention 256:269 the prevention of hyperoxaluria and calcium oxalate nephrolithiasis 256:322 The brush border Cl--oxalate exchanger SLC26A6 plays an essential role in mediating intestinal secretion of oxalate and is crucial for the maintenance of oxalate homeostasis and the prevention of hyperoxaluria and calcium oxalate nephrolithiasis. 27681177 5 42 theme carbohydrate 1052:1063 arg1 moieties 1065:1072 the carbohydrate moieties 1048:1072 the carbohydrate moieties 1048:1072 In vitro cell culture experiments were then used to elucidate the functional significance of the addition of the carbohydrate moieties. 27681177 2 43 theme Previous 325:332 arg1 studies 343:349 Previous in vitro studies 325:349 Previous in vitro studies 325:349 Previous in vitro studies have suggested that SLC26A6 is heavily N-glycosylated. 27681177 3 44 theme wide 499:502 arg1 variety 504:510 a wide variety 497:510 a wide variety of integral membrane proteins 497:540 N-linked glycosylation is known to critically affect folding, trafficking, and function in a wide variety of integral membrane proteins and could therefore potentially have a critical impact on SLC26A6 function and subsequent oxalate homeostasis. 27681177 3 44 theme wide 499:502 arg1 proteins 533:540 integral membrane proteins 515:540 integral membrane proteins 515:540 N-linked glycosylation is known to critically affect folding, trafficking, and function in a wide variety of integral membrane proteins and could therefore potentially have a critical impact on SLC26A6 function and subsequent oxalate homeostasis. 27681177 0 45 theme oxalate 49:55 arg1 SLC26A6 69:75 oxalate transporter SLC26A6 49:75 oxalate transporter SLC26A6 49:75 N-glycosylation critically regulates function of oxalate transporter SLC26A6. 27681177 3 46 theme membrane 524:531 arg1 proteins 533:540 integral membrane proteins 515:540 integral membrane proteins 515:540 N-linked glycosylation is known to critically affect folding, trafficking, and function in a wide variety of integral membrane proteins and could therefore potentially have a critical impact on SLC26A6 function and subsequent oxalate homeostasis. 27681177 3 47 theme oxalate 632:638 arg1 homeostasis 640:650 subsequent oxalate homeostasis 621:650 subsequent oxalate homeostasis 621:650 N-linked glycosylation is known to critically affect folding, trafficking, and function in a wide variety of integral membrane proteins and could therefore potentially have a critical impact on SLC26A6 function and subsequent oxalate homeostasis. 27681177 7 48 theme second 1429:1434 arg1 loop 1450:1453 the putative second extracellular loop 1416:1453 the putative second extracellular loop of SLC26A6 1416:1464 Functional studies of transfected SLC26A6 demonstrated that glycosylation at two sites in the putative second extracellular loop of SLC26A6 is critically important for chloride-dependent oxalate transport and that enzymatic deglycosylation of SLC26A6 expressed on the plasma membrane of intact cells strongly reduced oxalate transport activity. 27681177 4 49 theme studies 699:705 arg1 series 663:668 a series 661:668 a series of enzymatic deglycosylation studies 661:705 Through a series of enzymatic deglycosylation studies we confirmed that endogenously expressed mouse and human SLC26A6 are indeed glycosylated, that the oligosaccharides are principally attached via N-glycosidic linkage, and that there are tissue-specific differences in glycosylation. 27681177 5 50 theme In 939:940 arg1 experiments 961:971 In vitro cell culture experiments 939:971 In vitro cell culture experiments 939:971 In vitro cell culture experiments were then used to elucidate the functional significance of the addition of the carbohydrate moieties. 27681177 3 51 contain have 574:577 arg1 glycosylation 415:427 N-linked glycosylation 406:427 N-linked glycosylation 406:427 N-linked glycosylation is known to critically affect folding, trafficking, and function in a wide variety of integral membrane proteins and could therefore potentially have a critical impact on SLC26A6 function and subsequent oxalate homeostasis. 27681177 3 51 contain have 574:577 arg2 impact 590:595 a critical impact 579:595 a critical impact 579:595 N-linked glycosylation is known to critically affect folding, trafficking, and function in a wide variety of integral membrane proteins and could therefore potentially have a critical impact on SLC26A6 function and subsequent oxalate homeostasis. 27681177 4 52 gly glycosylated 783:794 arg1 mouse 748:752 mouse 748:752 mouse 748:752 Through a series of enzymatic deglycosylation studies we confirmed that endogenously expressed mouse and human SLC26A6 are indeed glycosylated, that the oligosaccharides are principally attached via N-glycosidic linkage, and that there are tissue-specific differences in glycosylation. 27681177 4 52 gly glycosylated 783:794 arg1 SLC26A6 764:770 human SLC26A6 758:770 human SLC26A6 758:770 Through a series of enzymatic deglycosylation studies we confirmed that endogenously expressed mouse and human SLC26A6 are indeed glycosylated, that the oligosaccharides are principally attached via N-glycosidic linkage, and that there are tissue-specific differences in glycosylation. 27681177 7 53 theme extracellular 1436:1448 arg1 loop 1450:1453 the putative second extracellular loop 1416:1453 the putative second extracellular loop of SLC26A6 1416:1464 Functional studies of transfected SLC26A6 demonstrated that glycosylation at two sites in the putative second extracellular loop of SLC26A6 is critically important for chloride-dependent oxalate transport and that enzymatic deglycosylation of SLC26A6 expressed on the plasma membrane of intact cells strongly reduced oxalate transport activity. 27681177 7 54 theme oxalate 1513:1519 arg1 transport 1521:1529 chloride-dependent oxalate transport 1494:1529 chloride-dependent oxalate transport 1494:1529 Functional studies of transfected SLC26A6 demonstrated that glycosylation at two sites in the putative second extracellular loop of SLC26A6 is critically important for chloride-dependent oxalate transport and that enzymatic deglycosylation of SLC26A6 expressed on the plasma membrane of intact cells strongly reduced oxalate transport activity. 27681177 4 55 theme deglycosylation 683:697 arg1 studies 699:705 enzymatic deglycosylation studies 673:705 enzymatic deglycosylation studies 673:705 Through a series of enzymatic deglycosylation studies we confirmed that endogenously expressed mouse and human SLC26A6 are indeed glycosylated, that the oligosaccharides are principally attached via N-glycosidic linkage, and that there are tissue-specific differences in glycosylation. 27681177 0 56 theme SLC26A6 69:75 arg1 function 37:44 function 37:44 function of oxalate transporter SLC26A6 37:75 N-glycosylation critically regulates function of oxalate transporter SLC26A6. 27681177 8 57 theme oxalate 1716:1722 arg1 function 1734:1741 oxalate transport function 1716:1741 oxalate transport function of SLC26A6 1716:1752 Taken together, these studies indicated that oxalate transport function of SLC26A6 is critically dependent on glycosylation and that exoglycosidase-mediated deglycosylation of SLC26A6 has the capacity to profoundly modulate SLC26A6 function. 27681177 7 58 theme Functional 1326:1335 arg1 studies 1337:1343 Functional studies 1326:1343 Functional studies of transfected SLC26A6 1326:1366 Functional studies of transfected SLC26A6 demonstrated that glycosylation at two sites in the putative second extracellular loop of SLC26A6 is critically important for chloride-dependent oxalate transport and that enzymatic deglycosylation of SLC26A6 expressed on the plasma membrane of intact cells strongly reduced oxalate transport activity. 27681177 4 59 theme tissue-specific 893:907 arg1 differences 909:919 tissue-specific differences 893:919 tissue-specific differences in glycosylation 893:936 Through a series of enzymatic deglycosylation studies we confirmed that endogenously expressed mouse and human SLC26A6 are indeed glycosylated, that the oligosaccharides are principally attached via N-glycosidic linkage, and that there are tissue-specific differences in glycosylation. 27681177 7 60 from sites 1407:1411 arg1 glycosylation 1386:1398 glycosylation 1386:1398 glycosylation at two sites in the putative second extracellular loop of SLC26A6 1386:1464 Functional studies of transfected SLC26A6 demonstrated that glycosylation at two sites in the putative second extracellular loop of SLC26A6 is critically important for chloride-dependent oxalate transport and that enzymatic deglycosylation of SLC26A6 expressed on the plasma membrane of intact cells strongly reduced oxalate transport activity. 27681177 7 60 from sites 1407:1411 arg1 loop 1450:1453 the putative second extracellular loop 1416:1453 the putative second extracellular loop of SLC26A6 1416:1464 Functional studies of transfected SLC26A6 demonstrated that glycosylation at two sites in the putative second extracellular loop of SLC26A6 is critically important for chloride-dependent oxalate transport and that enzymatic deglycosylation of SLC26A6 expressed on the plasma membrane of intact cells strongly reduced oxalate transport activity. 27681177 2 61 dep in 334:335 arg1 vitro 337:341 vitro 337:341 vitro 337:341 Previous in vitro studies have suggested that SLC26A6 is heavily N-glycosylated. 27681177 0 62 theme transporter 57:67 arg1 SLC26A6 69:75 oxalate transporter SLC26A6 49:75 oxalate transporter SLC26A6 49:75 N-glycosylation critically regulates function of oxalate transporter SLC26A6. 27681177 7 63 gly glycosylation 1386:1398 arg1 sites 1407:1411 two sites 1403:1411 two sites in the putative second extracellular loop of SLC26A6 1403:1464 Functional studies of transfected SLC26A6 demonstrated that glycosylation at two sites in the putative second extracellular loop of SLC26A6 is critically important for chloride-dependent oxalate transport and that enzymatic deglycosylation of SLC26A6 expressed on the plasma membrane of intact cells strongly reduced oxalate transport activity. 27681177 7 63 gly glycosylation 1386:1398 arg2 sites 1407:1411 two sites 1403:1411 two sites in the putative second extracellular loop of SLC26A6 1403:1464 Functional studies of transfected SLC26A6 demonstrated that glycosylation at two sites in the putative second extracellular loop of SLC26A6 is critically important for chloride-dependent oxalate transport and that enzymatic deglycosylation of SLC26A6 expressed on the plasma membrane of intact cells strongly reduced oxalate transport activity. 27681177 7 63 gly glycosylation 1386:1398 arg1 oxalate 1513:1519 chloride-dependent oxalate transport 1494:1529 chloride-dependent oxalate transport 1494:1529 Functional studies of transfected SLC26A6 demonstrated that glycosylation at two sites in the putative second extracellular loop of SLC26A6 is critically important for chloride-dependent oxalate transport and that enzymatic deglycosylation of SLC26A6 expressed on the plasma membrane of intact cells strongly reduced oxalate transport activity. 27681177 7 64 theme transport 1651:1659 arg1 activity 1661:1668 oxalate transport activity 1643:1668 oxalate transport activity 1643:1668 Functional studies of transfected SLC26A6 demonstrated that glycosylation at two sites in the putative second extracellular loop of SLC26A6 is critically important for chloride-dependent oxalate transport and that enzymatic deglycosylation of SLC26A6 expressed on the plasma membrane of intact cells strongly reduced oxalate transport activity. 27681177 3 65 theme subsequent 621:630 arg1 homeostasis 640:650 subsequent oxalate homeostasis 621:650 subsequent oxalate homeostasis 621:650 N-linked glycosylation is known to critically affect folding, trafficking, and function in a wide variety of integral membrane proteins and could therefore potentially have a critical impact on SLC26A6 function and subsequent oxalate homeostasis. 27681177 1 66 theme essential 134:142 arg1 role 144:147 an essential role 131:147 an essential role 131:147 The brush border Cl--oxalate exchanger SLC26A6 plays an essential role in mediating intestinal secretion of oxalate and is crucial for the maintenance of oxalate homeostasis and the prevention of hyperoxaluria and calcium oxalate nephrolithiasis. 27681177 7 67 theme SLC26A6 1360:1366 arg1 studies 1337:1343 Functional studies 1326:1343 Functional studies of transfected SLC26A6 1326:1366 Functional studies of transfected SLC26A6 demonstrated that glycosylation at two sites in the putative second extracellular loop of SLC26A6 is critically important for chloride-dependent oxalate transport and that enzymatic deglycosylation of SLC26A6 expressed on the plasma membrane of intact cells strongly reduced oxalate transport activity. 27681177 3 68 link N-linked 406:413 arg1 glycosylation 415:427 N-linked glycosylation 406:427 N-linked glycosylation 406:427 N-linked glycosylation is known to critically affect folding, trafficking, and function in a wide variety of integral membrane proteins and could therefore potentially have a critical impact on SLC26A6 function and subsequent oxalate homeostasis. 27681177 6 69 theme mutants 1122:1128 arg1 studies 1089:1095 Biotinylation studies 1075:1095 Biotinylation studies of SLC26A6 glycosylation mutants 1075:1128 Biotinylation studies of SLC26A6 glycosylation mutants indicated that glycosylation is not essential for cell surface delivery of SLC26A6 but suggested that it may affect the efficacy with which it is trafficked and maintained in the plasma membrane. 27681177 8 70 theme exoglycosidase-mediated 1804:1826 arg1 deglycosylation 1828:1842 exoglycosidase-mediated deglycosylation 1804:1842 exoglycosidase-mediated deglycosylation of SLC26A6 1804:1853 Taken together, these studies indicated that oxalate transport function of SLC26A6 is critically dependent on glycosylation and that exoglycosidase-mediated deglycosylation of SLC26A6 has the capacity to profoundly modulate SLC26A6 function. 27681177 1 71 theme oxalate 232:238 arg1 homeostasis 240:250 oxalate homeostasis 232:250 oxalate homeostasis 232:250 The brush border Cl--oxalate exchanger SLC26A6 plays an essential role in mediating intestinal secretion of oxalate and is crucial for the maintenance of oxalate homeostasis and the prevention of hyperoxaluria and calcium oxalate nephrolithiasis. 27681177 5 72 theme moieties 1065:1072 arg1 addition 1036:1043 the addition 1032:1043 the addition of the carbohydrate moieties 1032:1072 In vitro cell culture experiments were then used to elucidate the functional significance of the addition of the carbohydrate moieties. 27681177 4 73 theme N-glycosidic 852:863 arg1 linkage 865:871 N-glycosidic linkage 852:871 N-glycosidic linkage 852:871 Through a series of enzymatic deglycosylation studies we confirmed that endogenously expressed mouse and human SLC26A6 are indeed glycosylated, that the oligosaccharides are principally attached via N-glycosidic linkage, and that there are tissue-specific differences in glycosylation. 27681177 4 74 theme expressed 738:746 arg1 mouse 748:752 mouse 748:752 mouse 748:752 Through a series of enzymatic deglycosylation studies we confirmed that endogenously expressed mouse and human SLC26A6 are indeed glycosylated, that the oligosaccharides are principally attached via N-glycosidic linkage, and that there are tissue-specific differences in glycosylation. 27681177 8 75 theme SLC26A6 1847:1853 arg1 deglycosylation 1828:1842 exoglycosidase-mediated deglycosylation 1804:1842 exoglycosidase-mediated deglycosylation of SLC26A6 1804:1853 Taken together, these studies indicated that oxalate transport function of SLC26A6 is critically dependent on glycosylation and that exoglycosidase-mediated deglycosylation of SLC26A6 has the capacity to profoundly modulate SLC26A6 function. 27681177 1 76 theme homeostasis 240:250 arg1 maintenance 217:227 the maintenance 213:227 the maintenance of oxalate homeostasis 213:250 The brush border Cl--oxalate exchanger SLC26A6 plays an essential role in mediating intestinal secretion of oxalate and is crucial for the maintenance of oxalate homeostasis and the prevention of hyperoxaluria and calcium oxalate nephrolithiasis. 27681177 1 76 theme homeostasis 240:250 arg1 prevention 260:269 the prevention 256:269 the prevention of hyperoxaluria and calcium oxalate nephrolithiasis 256:322 The brush border Cl--oxalate exchanger SLC26A6 plays an essential role in mediating intestinal secretion of oxalate and is crucial for the maintenance of oxalate homeostasis and the prevention of hyperoxaluria and calcium oxalate nephrolithiasis. 27681177 6 77 theme SLC26A6 1205:1211 arg1 delivery 1193:1200 cell surface delivery 1180:1200 cell surface delivery of SLC26A6 1180:1211 Biotinylation studies of SLC26A6 glycosylation mutants indicated that glycosylation is not essential for cell surface delivery of SLC26A6 but suggested that it may affect the efficacy with which it is trafficked and maintained in the plasma membrane. 27681177 7 78 theme transfected 1348:1358 arg1 SLC26A6 1360:1366 transfected SLC26A6 1348:1366 transfected SLC26A6 1348:1366 Functional studies of transfected SLC26A6 demonstrated that glycosylation at two sites in the putative second extracellular loop of SLC26A6 is critically important for chloride-dependent oxalate transport and that enzymatic deglycosylation of SLC26A6 expressed on the plasma membrane of intact cells strongly reduced oxalate transport activity. 27681177 6 79 theme glycosylation 1108:1120 arg1 mutants 1122:1128 SLC26A6 glycosylation mutants 1100:1128 SLC26A6 glycosylation mutants 1100:1128 Biotinylation studies of SLC26A6 glycosylation mutants indicated that glycosylation is not essential for cell surface delivery of SLC26A6 but suggested that it may affect the efficacy with which it is trafficked and maintained in the plasma membrane. 27681177 6 80 theme Biotinylation 1075:1087 arg1 studies 1089:1095 Biotinylation studies 1075:1095 Biotinylation studies of SLC26A6 glycosylation mutants 1075:1128 Biotinylation studies of SLC26A6 glycosylation mutants indicated that glycosylation is not essential for cell surface delivery of SLC26A6 but suggested that it may affect the efficacy with which it is trafficked and maintained in the plasma membrane. 27681177 7 81 theme cells 1620:1624 arg1 membrane 1601:1608 the plasma membrane 1590:1608 the plasma membrane of intact cells 1590:1624 Functional studies of transfected SLC26A6 demonstrated that glycosylation at two sites in the putative second extracellular loop of SLC26A6 is critically important for chloride-dependent oxalate transport and that enzymatic deglycosylation of SLC26A6 expressed on the plasma membrane of intact cells strongly reduced oxalate transport activity. 27681177 7 82 theme SLC26A6 1458:1464 arg1 loop 1450:1453 the putative second extracellular loop 1416:1453 the putative second extracellular loop of SLC26A6 1416:1464 Functional studies of transfected SLC26A6 demonstrated that glycosylation at two sites in the putative second extracellular loop of SLC26A6 is critically important for chloride-dependent oxalate transport and that enzymatic deglycosylation of SLC26A6 expressed on the plasma membrane of intact cells strongly reduced oxalate transport activity. 27681177 1 83 theme intestinal 162:171 arg1 secretion 173:181 intestinal secretion 162:181 intestinal secretion of oxalate 162:192 The brush border Cl--oxalate exchanger SLC26A6 plays an essential role in mediating intestinal secretion of oxalate and is crucial for the maintenance of oxalate homeostasis and the prevention of hyperoxaluria and calcium oxalate nephrolithiasis. 27681177 6 84 theme SLC26A6 1100:1106 arg1 mutants 1122:1128 SLC26A6 glycosylation mutants 1100:1128 SLC26A6 glycosylation mutants 1100:1128 Biotinylation studies of SLC26A6 glycosylation mutants indicated that glycosylation is not essential for cell surface delivery of SLC26A6 but suggested that it may affect the efficacy with which it is trafficked and maintained in the plasma membrane. 26828122 8 0 dep domains 1703:1709 arg1 predicted 1714:1722 predicted 1714:1722 predicted by the TMHMM transmembrane helixes prediction program 1714:1776 The results also provide an indirect support for a membrane topology for hTPPT with 10 transmembrane domains as predicted by the TMHMM transmembrane helixes prediction program. 26828122 5 1 gly Glycosylation 967:979 arg1 hTPPT 984:988 hTPPT 984:988 hTPPT 984:988 Glycosylation of hTPPT was shown, by mean of site-directed mutagenesis, to occur at Asn(69), Asn(155), Asn(197), Asn(393), and Asn(416). 26828122 8 2 with topology 1662:1669 arg1 domains 1703:1709 10 transmembrane domains 1686:1709 10 transmembrane domains as predicted by the TMHMM transmembrane helixes prediction program 1686:1776 The results also provide an indirect support for a membrane topology for hTPPT with 10 transmembrane domains as predicted by the TMHMM transmembrane helixes prediction program. 26828122 3 3 gly N-glycosylation 576:590 arg2 sites 592:596 putative N-glycosylation sites 567:596 putative N-glycosylation sites 567:596 The hTPPT protein is predicted to have multiple TM domains with a number of putative N-glycosylation sites, but it is not known if the protein is actually glycosylated, and if so at which site, and their role in the functionality of the transporter. 26828122 3 4 theme hTPPT 495:499 arg1 protein 501:507 The hTPPT protein 491:507 The hTPPT protein 491:507 The hTPPT protein is predicted to have multiple TM domains with a number of putative N-glycosylation sites, but it is not known if the protein is actually glycosylated, and if so at which site, and their role in the functionality of the transporter. 26828122 6 5 from membrane 1361:1368 arg1 expression 1338:1347 expression 1338:1347 expression at the cell membrane as determined by live cell confocal imaging 1338:1412 However, only N-glycosylation at Asn(69), Asn(155), and Asn(393) appeared to be important for transporter functionality possibly through an effect on protein conformation and/or interaction with its ligand (but not through changes in expression at the cell membrane as determined by live cell confocal imaging). 26828122 6 5 from membrane 1361:1368 arg1 changes 1327:1333 changes 1327:1333 changes in expression at the cell membrane as determined by live cell confocal imaging 1327:1412 However, only N-glycosylation at Asn(69), Asn(155), and Asn(393) appeared to be important for transporter functionality possibly through an effect on protein conformation and/or interaction with its ligand (but not through changes in expression at the cell membrane as determined by live cell confocal imaging). 26828122 4 6 theme inhibiting 776:785 arg1 N-glycosylation 795:809 inhibiting de novo N-glycosylation 776:809 inhibiting de novo N-glycosylation in human colonic epithelial NCM460 cells with tunicamycin as well as enzymatic de-glycosylation 776:905 Using several approaches including inhibiting de novo N-glycosylation in human colonic epithelial NCM460 cells with tunicamycin as well as enzymatic de-glycosylation, we show that the hTPPT protein is, indeed, a glycoprotein. 26828122 3 7 theme multiple 530:537 arg1 domains 542:548 multiple TM domains 530:548 multiple TM domains 530:548 The hTPPT protein is predicted to have multiple TM domains with a number of putative N-glycosylation sites, but it is not known if the protein is actually glycosylated, and if so at which site, and their role in the functionality of the transporter. 26828122 6 8 theme protein 1254:1260 arg1 conformation 1262:1273 protein conformation 1254:1273 protein conformation 1254:1273 However, only N-glycosylation at Asn(69), Asn(155), and Asn(393) appeared to be important for transporter functionality possibly through an effect on protein conformation and/or interaction with its ligand (but not through changes in expression at the cell membrane as determined by live cell confocal imaging). 26828122 5 9 theme hTPPT 984:988 arg1 Glycosylation 967:979 Glycosylation 967:979 Glycosylation of hTPPT 967:988 Glycosylation of hTPPT was shown, by mean of site-directed mutagenesis, to occur at Asn(69), Asn(155), Asn(197), Asn(393), and Asn(416). 26828122 6 10 with interaction 1282:1292 arg1 ligand 1303:1308 its ligand 1299:1308 its ligand (but not through changes in expression at the cell membrane as determined by live cell confocal imaging) 1299:1413 However, only N-glycosylation at Asn(69), Asn(155), and Asn(393) appeared to be important for transporter functionality possibly through an effect on protein conformation and/or interaction with its ligand (but not through changes in expression at the cell membrane as determined by live cell confocal imaging). 26828122 4 11 theme colonic 820:826 arg1 cells 846:850 human colonic epithelial NCM460 cells 814:850 human colonic epithelial NCM460 cells with tunicamycin 814:867 Using several approaches including inhibiting de novo N-glycosylation in human colonic epithelial NCM460 cells with tunicamycin as well as enzymatic de-glycosylation, we show that the hTPPT protein is, indeed, a glycoprotein. 26828122 8 12 theme indirect 1630:1637 arg1 support 1639:1645 an indirect support 1627:1645 an indirect support for a membrane topology for hTPPT with 10 transmembrane domains as predicted by the TMHMM transmembrane helixes prediction program 1627:1776 The results also provide an indirect support for a membrane topology for hTPPT with 10 transmembrane domains as predicted by the TMHMM transmembrane helixes prediction program. 26828122 4 13 gly glycoprotein 953:964 arg1 protein 931:937 the hTPPT protein 921:937 the hTPPT protein 921:937 Using several approaches including inhibiting de novo N-glycosylation in human colonic epithelial NCM460 cells with tunicamycin as well as enzymatic de-glycosylation, we show that the hTPPT protein is, indeed, a glycoprotein. 26828122 4 13 gly glycoprotein 953:964 arg1 glycoprotein 953:964 a glycoprotein 951:964 a glycoprotein 951:964 Using several approaches including inhibiting de novo N-glycosylation in human colonic epithelial NCM460 cells with tunicamycin as well as enzymatic de-glycosylation, we show that the hTPPT protein is, indeed, a glycoprotein. 26828122 7 14 theme first 1454:1458 arg1 time 1460:1463 the first time 1450:1463 the first time 1450:1463 Results of this study showed, for the first time, that the hTPPT is glycosylated and that N-linked glycosylation occurs at multiple sites with some of them being important for function. 26828122 4 15 theme NCM460 839:844 arg1 cells 846:850 human colonic epithelial NCM460 cells 814:850 human colonic epithelial NCM460 cells with tunicamycin 814:867 Using several approaches including inhibiting de novo N-glycosylation in human colonic epithelial NCM460 cells with tunicamycin as well as enzymatic de-glycosylation, we show that the hTPPT protein is, indeed, a glycoprotein. 26828122 6 16 theme confocal 1397:1404 arg1 imaging 1406:1412 live cell confocal imaging 1387:1412 live cell confocal imaging 1387:1412 However, only N-glycosylation at Asn(69), Asn(155), and Asn(393) appeared to be important for transporter functionality possibly through an effect on protein conformation and/or interaction with its ligand (but not through changes in expression at the cell membrane as determined by live cell confocal imaging). 26828122 6 17 from Asn 1160:1162 arg1 N-glycosylation 1118:1132 only N-glycosylation 1113:1132 only N-glycosylation at Asn(69), Asn(155), and Asn(393) 1113:1167 However, only N-glycosylation at Asn(69), Asn(155), and Asn(393) appeared to be important for transporter functionality possibly through an effect on protein conformation and/or interaction with its ligand (but not through changes in expression at the cell membrane as determined by live cell confocal imaging). 26828122 3 18 theme N-glycosylation 576:590 arg1 sites 592:596 putative N-glycosylation sites 567:596 putative N-glycosylation sites 567:596 The hTPPT protein is predicted to have multiple TM domains with a number of putative N-glycosylation sites, but it is not known if the protein is actually glycosylated, and if so at which site, and their role in the functionality of the transporter. 26828122 6 19 from changes 1327:1333 arg1 expression 1338:1347 expression 1338:1347 expression at the cell membrane as determined by live cell confocal imaging 1338:1412 However, only N-glycosylation at Asn(69), Asn(155), and Asn(393) appeared to be important for transporter functionality possibly through an effect on protein conformation and/or interaction with its ligand (but not through changes in expression at the cell membrane as determined by live cell confocal imaging). 26828122 6 19 from changes 1327:1333 arg1 membrane 1361:1368 the cell membrane 1352:1368 the cell membrane as determined by live cell confocal imaging 1352:1412 However, only N-glycosylation at Asn(69), Asn(155), and Asn(393) appeared to be important for transporter functionality possibly through an effect on protein conformation and/or interaction with its ligand (but not through changes in expression at the cell membrane as determined by live cell confocal imaging). 26828122 2 20 theme membrane 461:468 arg1 epithelia 480:488 epithelia 480:488 epithelia 480:488 The hTPPT is highly expressed in the colon, but not in other regions of the intestinal tract and is localized exclusively at the apical membrane domain of epithelia. 26828122 2 20 theme membrane 461:468 arg1 domain 470:475 the apical membrane domain 450:475 the apical membrane domain of epithelia 450:488 The hTPPT is highly expressed in the colon, but not in other regions of the intestinal tract and is localized exclusively at the apical membrane domain of epithelia. 26828122 6 21 theme live 1387:1390 arg1 imaging 1406:1412 live cell confocal imaging 1387:1412 live cell confocal imaging 1387:1412 However, only N-glycosylation at Asn(69), Asn(155), and Asn(393) appeared to be important for transporter functionality possibly through an effect on protein conformation and/or interaction with its ligand (but not through changes in expression at the cell membrane as determined by live cell confocal imaging). 26828122 8 22 theme membrane 1653:1660 arg1 topology 1662:1669 a membrane topology 1651:1669 a membrane topology for hTPPT with 10 transmembrane domains as predicted by the TMHMM transmembrane helixes prediction program 1651:1776 The results also provide an indirect support for a membrane topology for hTPPT with 10 transmembrane domains as predicted by the TMHMM transmembrane helixes prediction program. 26828122 6 23 from Asn 1146:1148 arg1 N-glycosylation 1118:1132 only N-glycosylation 1113:1132 only N-glycosylation at Asn(69), Asn(155), and Asn(393) 1113:1167 However, only N-glycosylation at Asn(69), Asn(155), and Asn(393) appeared to be important for transporter functionality possibly through an effect on protein conformation and/or interaction with its ligand (but not through changes in expression at the cell membrane as determined by live cell confocal imaging). 26828122 1 24 theme identified 150:159 arg1 transporter 190:200 The recently identified human thiamine pyrophosphate transporter 137:200 The recently identified human thiamine pyrophosphate transporter (hTPPT; product of the SLC44A4 gene) 137:237 The recently identified human thiamine pyrophosphate transporter (hTPPT; product of the SLC44A4 gene) is responsible for absorption of the microbiota-generated TPP in the large intestine. 26828122 1 24 theme identified 150:159 arg1 responsible 242:252 responsible 242:252 responsible 242:252 The recently identified human thiamine pyrophosphate transporter (hTPPT; product of the SLC44A4 gene) is responsible for absorption of the microbiota-generated TPP in the large intestine. 26828122 8 25 theme transmembrane 1689:1701 arg1 domains 1703:1709 10 transmembrane domains 1686:1709 10 transmembrane domains as predicted by the TMHMM transmembrane helixes prediction program 1686:1776 The results also provide an indirect support for a membrane topology for hTPPT with 10 transmembrane domains as predicted by the TMHMM transmembrane helixes prediction program. 26828122 6 26 theme cell 1356:1359 arg1 membrane 1361:1368 the cell membrane 1352:1368 the cell membrane as determined by live cell confocal imaging 1352:1412 However, only N-glycosylation at Asn(69), Asn(155), and Asn(393) appeared to be important for transporter functionality possibly through an effect on protein conformation and/or interaction with its ligand (but not through changes in expression at the cell membrane as determined by live cell confocal imaging). 26828122 0 27 gly glycoprotein 66:77 arg1 transporter 41:51 The human colonic thiamine pyrophosphate transporter 0:51 The human colonic thiamine pyrophosphate transporter (hTPPT) 0:59 The human colonic thiamine pyrophosphate transporter (hTPPT) is a glycoprotein and N-linked glycosylation is important for its function. 26828122 0 27 gly glycoprotein 66:77 arg1 glycoprotein 66:77 a glycoprotein 64:77 a glycoprotein 64:77 The human colonic thiamine pyrophosphate transporter (hTPPT) is a glycoprotein and N-linked glycosylation is important for its function. 26828122 2 28 theme tract 412:416 arg1 regions 386:392 other regions 380:392 other regions of the intestinal tract 380:416 The hTPPT is highly expressed in the colon, but not in other regions of the intestinal tract and is localized exclusively at the apical membrane domain of epithelia. 26828122 3 29 contain have 525:528 arg1 protein 501:507 The hTPPT protein 491:507 The hTPPT protein 491:507 The hTPPT protein is predicted to have multiple TM domains with a number of putative N-glycosylation sites, but it is not known if the protein is actually glycosylated, and if so at which site, and their role in the functionality of the transporter. 26828122 3 29 contain have 525:528 arg2 domains 542:548 multiple TM domains 530:548 multiple TM domains 530:548 The hTPPT protein is predicted to have multiple TM domains with a number of putative N-glycosylation sites, but it is not known if the protein is actually glycosylated, and if so at which site, and their role in the functionality of the transporter. 26828122 7 30 link N-linked 1506:1513 arg1 glycosylation 1515:1527 N-linked glycosylation 1506:1527 N-linked glycosylation 1506:1527 Results of this study showed, for the first time, that the hTPPT is glycosylated and that N-linked glycosylation occurs at multiple sites with some of them being important for function. 26828122 0 31 theme colonic 10:16 arg1 transporter 41:51 The human colonic thiamine pyrophosphate transporter 0:51 The human colonic thiamine pyrophosphate transporter (hTPPT) 0:59 The human colonic thiamine pyrophosphate transporter (hTPPT) is a glycoprotein and N-linked glycosylation is important for its function. 26828122 0 31 theme colonic 10:16 arg1 glycoprotein 66:77 a glycoprotein 64:77 a glycoprotein 64:77 The human colonic thiamine pyrophosphate transporter (hTPPT) is a glycoprotein and N-linked glycosylation is important for its function. 26828122 0 31 theme colonic 10:16 arg1 hTPPT 54:58 hTPPT 54:58 hTPPT 54:58 The human colonic thiamine pyrophosphate transporter (hTPPT) is a glycoprotein and N-linked glycosylation is important for its function. 26828122 4 32 gly de-glycosylation 890:905 arg1 cells 846:850 human colonic epithelial NCM460 cells 814:850 human colonic epithelial NCM460 cells with tunicamycin 814:867 Using several approaches including inhibiting de novo N-glycosylation in human colonic epithelial NCM460 cells with tunicamycin as well as enzymatic de-glycosylation, we show that the hTPPT protein is, indeed, a glycoprotein. 26828122 4 33 theme hTPPT 925:929 arg1 protein 931:937 the hTPPT protein 921:937 the hTPPT protein 921:937 Using several approaches including inhibiting de novo N-glycosylation in human colonic epithelial NCM460 cells with tunicamycin as well as enzymatic de-glycosylation, we show that the hTPPT protein is, indeed, a glycoprotein. 26828122 4 33 theme hTPPT 925:929 arg1 glycoprotein 953:964 a glycoprotein 951:964 a glycoprotein 951:964 Using several approaches including inhibiting de novo N-glycosylation in human colonic epithelial NCM460 cells with tunicamycin as well as enzymatic de-glycosylation, we show that the hTPPT protein is, indeed, a glycoprotein. 26828122 3 34 gly glycosylated 646:657 arg1 protein 626:632 the protein 622:632 the protein 622:632 The hTPPT protein is predicted to have multiple TM domains with a number of putative N-glycosylation sites, but it is not known if the protein is actually glycosylated, and if so at which site, and their role in the functionality of the transporter. 26828122 0 35 theme pyrophosphate 27:39 arg1 transporter 41:51 The human colonic thiamine pyrophosphate transporter 0:51 The human colonic thiamine pyrophosphate transporter (hTPPT) 0:59 The human colonic thiamine pyrophosphate transporter (hTPPT) is a glycoprotein and N-linked glycosylation is important for its function. 26828122 0 35 theme pyrophosphate 27:39 arg1 glycoprotein 66:77 a glycoprotein 64:77 a glycoprotein 64:77 The human colonic thiamine pyrophosphate transporter (hTPPT) is a glycoprotein and N-linked glycosylation is important for its function. 26828122 0 35 theme pyrophosphate 27:39 arg1 hTPPT 54:58 hTPPT 54:58 hTPPT 54:58 The human colonic thiamine pyrophosphate transporter (hTPPT) is a glycoprotein and N-linked glycosylation is important for its function. 26828122 1 36 theme TPP 297:299 arg1 absorption 258:267 absorption 258:267 absorption of the microbiota-generated TPP in the large intestine 258:322 The recently identified human thiamine pyrophosphate transporter (hTPPT; product of the SLC44A4 gene) is responsible for absorption of the microbiota-generated TPP in the large intestine. 26828122 8 37 theme helixes 1751:1757 arg1 program 1770:1776 the TMHMM transmembrane helixes prediction program 1727:1776 the TMHMM transmembrane helixes prediction program 1727:1776 The results also provide an indirect support for a membrane topology for hTPPT with 10 transmembrane domains as predicted by the TMHMM transmembrane helixes prediction program. 26828122 7 38 theme multiple 1539:1546 arg1 sites 1548:1552 multiple sites 1539:1552 multiple sites 1539:1552 Results of this study showed, for the first time, that the hTPPT is glycosylated and that N-linked glycosylation occurs at multiple sites with some of them being important for function. 26828122 1 39 theme thiamine 167:174 arg1 transporter 190:200 The recently identified human thiamine pyrophosphate transporter 137:200 The recently identified human thiamine pyrophosphate transporter (hTPPT; product of the SLC44A4 gene) 137:237 The recently identified human thiamine pyrophosphate transporter (hTPPT; product of the SLC44A4 gene) is responsible for absorption of the microbiota-generated TPP in the large intestine. 26828122 1 39 theme thiamine 167:174 arg1 responsible 242:252 responsible 242:252 responsible 242:252 The recently identified human thiamine pyrophosphate transporter (hTPPT; product of the SLC44A4 gene) is responsible for absorption of the microbiota-generated TPP in the large intestine. 26828122 1 40 theme SLC44A4 225:231 arg1 gene 233:236 the SLC44A4 gene 221:236 the SLC44A4 gene 221:236 The recently identified human thiamine pyrophosphate transporter (hTPPT; product of the SLC44A4 gene) is responsible for absorption of the microbiota-generated TPP in the large intestine. 26828122 7 41 theme N-linked 1506:1513 arg1 glycosylation 1515:1527 N-linked glycosylation 1506:1527 N-linked glycosylation 1506:1527 Results of this study showed, for the first time, that the hTPPT is glycosylated and that N-linked glycosylation occurs at multiple sites with some of them being important for function. 26828122 4 42 from de-glycosylation 890:905 arg1 cells 846:850 human colonic epithelial NCM460 cells 814:850 human colonic epithelial NCM460 cells with tunicamycin 814:867 Using several approaches including inhibiting de novo N-glycosylation in human colonic epithelial NCM460 cells with tunicamycin as well as enzymatic de-glycosylation, we show that the hTPPT protein is, indeed, a glycoprotein. 26828122 4 43 theme de 787:788 arg1 N-glycosylation 795:809 inhibiting de novo N-glycosylation 776:809 inhibiting de novo N-glycosylation in human colonic epithelial NCM460 cells with tunicamycin as well as enzymatic de-glycosylation 776:905 Using several approaches including inhibiting de novo N-glycosylation in human colonic epithelial NCM460 cells with tunicamycin as well as enzymatic de-glycosylation, we show that the hTPPT protein is, indeed, a glycoprotein. 26828122 2 44 located localized 425:433 arg1 epithelia 480:488 epithelia 480:488 epithelia 480:488 The hTPPT is highly expressed in the colon, but not in other regions of the intestinal tract and is localized exclusively at the apical membrane domain of epithelia. 26828122 2 44 located localized 425:433 arg2 hTPPT 329:333 The hTPPT 325:333 The hTPPT 325:333 The hTPPT is highly expressed in the colon, but not in other regions of the intestinal tract and is localized exclusively at the apical membrane domain of epithelia. 26828122 2 44 located localized 425:433 arg1 domain 470:475 the apical membrane domain 450:475 the apical membrane domain of epithelia 450:488 The hTPPT is highly expressed in the colon, but not in other regions of the intestinal tract and is localized exclusively at the apical membrane domain of epithelia. 26828122 1 45 theme pyrophosphate 176:188 arg1 transporter 190:200 The recently identified human thiamine pyrophosphate transporter 137:200 The recently identified human thiamine pyrophosphate transporter (hTPPT; product of the SLC44A4 gene) 137:237 The recently identified human thiamine pyrophosphate transporter (hTPPT; product of the SLC44A4 gene) is responsible for absorption of the microbiota-generated TPP in the large intestine. 26828122 1 45 theme pyrophosphate 176:188 arg1 responsible 242:252 responsible 242:252 responsible 242:252 The recently identified human thiamine pyrophosphate transporter (hTPPT; product of the SLC44A4 gene) is responsible for absorption of the microbiota-generated TPP in the large intestine. 26828122 1 46 theme human 161:165 arg1 transporter 190:200 The recently identified human thiamine pyrophosphate transporter 137:200 The recently identified human thiamine pyrophosphate transporter (hTPPT; product of the SLC44A4 gene) 137:237 The recently identified human thiamine pyrophosphate transporter (hTPPT; product of the SLC44A4 gene) is responsible for absorption of the microbiota-generated TPP in the large intestine. 26828122 1 46 theme human 161:165 arg1 responsible 242:252 responsible 242:252 responsible 242:252 The recently identified human thiamine pyrophosphate transporter (hTPPT; product of the SLC44A4 gene) is responsible for absorption of the microbiota-generated TPP in the large intestine. 26828122 4 47 dep de 787:788 arg1 novo 790:793 novo 790:793 novo 790:793 Using several approaches including inhibiting de novo N-glycosylation in human colonic epithelial NCM460 cells with tunicamycin as well as enzymatic de-glycosylation, we show that the hTPPT protein is, indeed, a glycoprotein. 26828122 4 48 theme several 747:753 arg1 de-glycosylation 890:905 enzymatic de-glycosylation 880:905 inhibiting de novo N-glycosylation in human colonic epithelial NCM460 cells with tunicamycin as well as enzymatic de-glycosylation 776:905 Using several approaches including inhibiting de novo N-glycosylation in human colonic epithelial NCM460 cells with tunicamycin as well as enzymatic de-glycosylation, we show that the hTPPT protein is, indeed, a glycoprotein. 26828122 4 48 theme several 747:753 arg1 N-glycosylation 795:809 inhibiting de novo N-glycosylation 776:809 inhibiting de novo N-glycosylation in human colonic epithelial NCM460 cells with tunicamycin as well as enzymatic de-glycosylation 776:905 Using several approaches including inhibiting de novo N-glycosylation in human colonic epithelial NCM460 cells with tunicamycin as well as enzymatic de-glycosylation, we show that the hTPPT protein is, indeed, a glycoprotein. 26828122 4 48 theme several 747:753 arg1 approaches 755:764 several approaches 747:764 several approaches including inhibiting de novo N-glycosylation in human colonic epithelial NCM460 cells with tunicamycin as well as enzymatic de-glycosylation 747:905 Using several approaches including inhibiting de novo N-glycosylation in human colonic epithelial NCM460 cells with tunicamycin as well as enzymatic de-glycosylation, we show that the hTPPT protein is, indeed, a glycoprotein. 26828122 1 49 from absorption 258:267 arg1 intestine 314:322 the large intestine 304:322 the large intestine 304:322 The recently identified human thiamine pyrophosphate transporter (hTPPT; product of the SLC44A4 gene) is responsible for absorption of the microbiota-generated TPP in the large intestine. 26828122 4 50 gly N-glycosylation 795:809 arg1 cells 846:850 human colonic epithelial NCM460 cells 814:850 human colonic epithelial NCM460 cells with tunicamycin 814:867 Using several approaches including inhibiting de novo N-glycosylation in human colonic epithelial NCM460 cells with tunicamycin as well as enzymatic de-glycosylation, we show that the hTPPT protein is, indeed, a glycoprotein. 26828122 6 51 gly N-glycosylation 1118:1132 arg1 Asn 1160:1162 Asn(393) 1160:1167 Asn(393) 1160:1167 However, only N-glycosylation at Asn(69), Asn(155), and Asn(393) appeared to be important for transporter functionality possibly through an effect on protein conformation and/or interaction with its ligand (but not through changes in expression at the cell membrane as determined by live cell confocal imaging). 26828122 6 51 gly N-glycosylation 1118:1132 arg1 Asn 1146:1148 Asn(155) 1146:1153 Asn(155) 1146:1153 However, only N-glycosylation at Asn(69), Asn(155), and Asn(393) appeared to be important for transporter functionality possibly through an effect on protein conformation and/or interaction with its ligand (but not through changes in expression at the cell membrane as determined by live cell confocal imaging). 26828122 6 51 gly N-glycosylation 1118:1132 arg2 Asn 1146:1148 Asn(155) 1146:1153 Asn(155) 1146:1153 However, only N-glycosylation at Asn(69), Asn(155), and Asn(393) appeared to be important for transporter functionality possibly through an effect on protein conformation and/or interaction with its ligand (but not through changes in expression at the cell membrane as determined by live cell confocal imaging). 26828122 6 51 gly N-glycosylation 1118:1132 arg1 Asn 1137:1139 Asn(69) 1137:1143 Asn(69) 1137:1143 However, only N-glycosylation at Asn(69), Asn(155), and Asn(393) appeared to be important for transporter functionality possibly through an effect on protein conformation and/or interaction with its ligand (but not through changes in expression at the cell membrane as determined by live cell confocal imaging). 26828122 6 51 gly N-glycosylation 1118:1132 arg2 Asn 1160:1162 Asn(393) 1160:1167 Asn(393) 1160:1167 However, only N-glycosylation at Asn(69), Asn(155), and Asn(393) appeared to be important for transporter functionality possibly through an effect on protein conformation and/or interaction with its ligand (but not through changes in expression at the cell membrane as determined by live cell confocal imaging). 26828122 6 51 gly N-glycosylation 1118:1132 arg1 transporter 1198:1208 transporter functionality 1198:1222 transporter functionality 1198:1222 However, only N-glycosylation at Asn(69), Asn(155), and Asn(393) appeared to be important for transporter functionality possibly through an effect on protein conformation and/or interaction with its ligand (but not through changes in expression at the cell membrane as determined by live cell confocal imaging). 26828122 6 51 gly N-glycosylation 1118:1132 arg2 Asn 1137:1139 Asn(69) 1137:1143 Asn(69) 1137:1143 However, only N-glycosylation at Asn(69), Asn(155), and Asn(393) appeared to be important for transporter functionality possibly through an effect on protein conformation and/or interaction with its ligand (but not through changes in expression at the cell membrane as determined by live cell confocal imaging). 26828122 7 52 gly glycosylation 1515:1527 arg2 sites 1548:1552 multiple sites 1539:1552 multiple sites 1539:1552 Results of this study showed, for the first time, that the hTPPT is glycosylated and that N-linked glycosylation occurs at multiple sites with some of them being important for function. 26828122 6 53 theme only 1113:1116 arg1 N-glycosylation 1118:1132 only N-glycosylation 1113:1132 only N-glycosylation at Asn(69), Asn(155), and Asn(393) 1113:1167 However, only N-glycosylation at Asn(69), Asn(155), and Asn(393) appeared to be important for transporter functionality possibly through an effect on protein conformation and/or interaction with its ligand (but not through changes in expression at the cell membrane as determined by live cell confocal imaging). 26828122 3 54 theme TM 539:540 arg1 domains 542:548 multiple TM domains 530:548 multiple TM domains 530:548 The hTPPT protein is predicted to have multiple TM domains with a number of putative N-glycosylation sites, but it is not known if the protein is actually glycosylated, and if so at which site, and their role in the functionality of the transporter. 26828122 4 55 theme human 814:818 arg1 cells 846:850 human colonic epithelial NCM460 cells 814:850 human colonic epithelial NCM460 cells with tunicamycin 814:867 Using several approaches including inhibiting de novo N-glycosylation in human colonic epithelial NCM460 cells with tunicamycin as well as enzymatic de-glycosylation, we show that the hTPPT protein is, indeed, a glycoprotein. 26828122 3 56 theme putative 567:574 arg1 sites 592:596 putative N-glycosylation sites 567:596 putative N-glycosylation sites 567:596 The hTPPT protein is predicted to have multiple TM domains with a number of putative N-glycosylation sites, but it is not known if the protein is actually glycosylated, and if so at which site, and their role in the functionality of the transporter. 26828122 4 57 theme epithelial 828:837 arg1 cells 846:850 human colonic epithelial NCM460 cells 814:850 human colonic epithelial NCM460 cells with tunicamycin 814:867 Using several approaches including inhibiting de novo N-glycosylation in human colonic epithelial NCM460 cells with tunicamycin as well as enzymatic de-glycosylation, we show that the hTPPT protein is, indeed, a glycoprotein. 26828122 6 58 theme cell 1392:1395 arg1 imaging 1406:1412 live cell confocal imaging 1387:1412 live cell confocal imaging 1387:1412 However, only N-glycosylation at Asn(69), Asn(155), and Asn(393) appeared to be important for transporter functionality possibly through an effect on protein conformation and/or interaction with its ligand (but not through changes in expression at the cell membrane as determined by live cell confocal imaging). 26828122 7 59 theme study 1432:1436 arg1 Results 1416:1422 Results 1416:1422 Results of this study 1416:1436 Results of this study showed, for the first time, that the hTPPT is glycosylated and that N-linked glycosylation occurs at multiple sites with some of them being important for function. 26828122 2 60 theme apical 454:459 arg1 epithelia 480:488 epithelia 480:488 epithelia 480:488 The hTPPT is highly expressed in the colon, but not in other regions of the intestinal tract and is localized exclusively at the apical membrane domain of epithelia. 26828122 2 60 theme apical 454:459 arg1 domain 470:475 the apical membrane domain 450:475 the apical membrane domain of epithelia 450:488 The hTPPT is highly expressed in the colon, but not in other regions of the intestinal tract and is localized exclusively at the apical membrane domain of epithelia. 26828122 4 61 from N-glycosylation 795:809 arg1 cells 846:850 human colonic epithelial NCM460 cells 814:850 human colonic epithelial NCM460 cells with tunicamycin 814:867 Using several approaches including inhibiting de novo N-glycosylation in human colonic epithelial NCM460 cells with tunicamycin as well as enzymatic de-glycosylation, we show that the hTPPT protein is, indeed, a glycoprotein. 26828122 0 62 theme N-linked 83:90 arg1 glycosylation 92:104 N-linked glycosylation 83:104 N-linked glycosylation 83:104 The human colonic thiamine pyrophosphate transporter (hTPPT) is a glycoprotein and N-linked glycosylation is important for its function. 26828122 6 63 dep changes 1327:1333 arg1 not 1315:1317 not 1315:1317 not 1315:1317 However, only N-glycosylation at Asn(69), Asn(155), and Asn(393) appeared to be important for transporter functionality possibly through an effect on protein conformation and/or interaction with its ligand (but not through changes in expression at the cell membrane as determined by live cell confocal imaging). 26828122 7 64 gly glycosylated 1484:1495 arg1 hTPPT 1475:1479 the hTPPT 1471:1479 the hTPPT 1471:1479 Results of this study showed, for the first time, that the hTPPT is glycosylated and that N-linked glycosylation occurs at multiple sites with some of them being important for function. 26828122 2 65 theme epithelia 480:488 arg1 epithelia 480:488 epithelia 480:488 epithelia 480:488 The hTPPT is highly expressed in the colon, but not in other regions of the intestinal tract and is localized exclusively at the apical membrane domain of epithelia. 26828122 2 65 theme epithelia 480:488 arg1 domain 470:475 the apical membrane domain 450:475 the apical membrane domain of epithelia 450:488 The hTPPT is highly expressed in the colon, but not in other regions of the intestinal tract and is localized exclusively at the apical membrane domain of epithelia. 26828122 3 66 from role 695:698 arg1 functionality 707:719 the functionality 703:719 the functionality of the transporter 703:738 The hTPPT protein is predicted to have multiple TM domains with a number of putative N-glycosylation sites, but it is not known if the protein is actually glycosylated, and if so at which site, and their role in the functionality of the transporter. 26828122 3 67 theme transporter 728:738 arg1 functionality 707:719 the functionality 703:719 the functionality of the transporter 703:738 The hTPPT protein is predicted to have multiple TM domains with a number of putative N-glycosylation sites, but it is not known if the protein is actually glycosylated, and if so at which site, and their role in the functionality of the transporter. 26828122 6 68 from Asn 1137:1139 arg1 N-glycosylation 1118:1132 only N-glycosylation 1113:1132 only N-glycosylation at Asn(69), Asn(155), and Asn(393) 1113:1167 However, only N-glycosylation at Asn(69), Asn(155), and Asn(393) appeared to be important for transporter functionality possibly through an effect on protein conformation and/or interaction with its ligand (but not through changes in expression at the cell membrane as determined by live cell confocal imaging). 26828122 4 69 theme enzymatic 880:888 arg1 de-glycosylation 890:905 enzymatic de-glycosylation 880:905 inhibiting de novo N-glycosylation in human colonic epithelial NCM460 cells with tunicamycin as well as enzymatic de-glycosylation 776:905 Using several approaches including inhibiting de novo N-glycosylation in human colonic epithelial NCM460 cells with tunicamycin as well as enzymatic de-glycosylation, we show that the hTPPT protein is, indeed, a glycoprotein. 26828122 0 70 theme human 4:8 arg1 transporter 41:51 The human colonic thiamine pyrophosphate transporter 0:51 The human colonic thiamine pyrophosphate transporter (hTPPT) 0:59 The human colonic thiamine pyrophosphate transporter (hTPPT) is a glycoprotein and N-linked glycosylation is important for its function. 26828122 0 70 theme human 4:8 arg1 glycoprotein 66:77 a glycoprotein 64:77 a glycoprotein 64:77 The human colonic thiamine pyrophosphate transporter (hTPPT) is a glycoprotein and N-linked glycosylation is important for its function. 26828122 0 70 theme human 4:8 arg1 hTPPT 54:58 hTPPT 54:58 hTPPT 54:58 The human colonic thiamine pyrophosphate transporter (hTPPT) is a glycoprotein and N-linked glycosylation is important for its function. 26828122 5 71 theme site-directed 1012:1024 arg1 mutagenesis 1026:1036 site-directed mutagenesis 1012:1036 site-directed mutagenesis 1012:1036 Glycosylation of hTPPT was shown, by mean of site-directed mutagenesis, to occur at Asn(69), Asn(155), Asn(197), Asn(393), and Asn(416). 26828122 6 72 from effect 1244:1249 arg1 interaction 1282:1292 interaction 1282:1292 interaction with its ligand (but not through changes in expression at the cell membrane as determined by live cell confocal imaging) 1282:1413 However, only N-glycosylation at Asn(69), Asn(155), and Asn(393) appeared to be important for transporter functionality possibly through an effect on protein conformation and/or interaction with its ligand (but not through changes in expression at the cell membrane as determined by live cell confocal imaging). 26828122 6 72 from effect 1244:1249 arg1 conformation 1262:1273 protein conformation 1254:1273 protein conformation 1254:1273 However, only N-glycosylation at Asn(69), Asn(155), and Asn(393) appeared to be important for transporter functionality possibly through an effect on protein conformation and/or interaction with its ligand (but not through changes in expression at the cell membrane as determined by live cell confocal imaging). 26828122 4 73 with cells 846:850 arg1 tunicamycin 857:867 tunicamycin 857:867 tunicamycin 857:867 Using several approaches including inhibiting de novo N-glycosylation in human colonic epithelial NCM460 cells with tunicamycin as well as enzymatic de-glycosylation, we show that the hTPPT protein is, indeed, a glycoprotein. 26828122 2 74 theme intestinal 401:410 arg1 tract 412:416 the intestinal tract 397:416 the intestinal tract 397:416 The hTPPT is highly expressed in the colon, but not in other regions of the intestinal tract and is localized exclusively at the apical membrane domain of epithelia. 26828122 3 75 from site 679:682 arg1 functionality 707:719 the functionality 703:719 the functionality of the transporter 703:738 The hTPPT protein is predicted to have multiple TM domains with a number of putative N-glycosylation sites, but it is not known if the protein is actually glycosylated, and if so at which site, and their role in the functionality of the transporter. 26828122 0 76 theme thiamine 18:25 arg1 transporter 41:51 The human colonic thiamine pyrophosphate transporter 0:51 The human colonic thiamine pyrophosphate transporter (hTPPT) 0:59 The human colonic thiamine pyrophosphate transporter (hTPPT) is a glycoprotein and N-linked glycosylation is important for its function. 26828122 0 76 theme thiamine 18:25 arg1 glycoprotein 66:77 a glycoprotein 64:77 a glycoprotein 64:77 The human colonic thiamine pyrophosphate transporter (hTPPT) is a glycoprotein and N-linked glycosylation is important for its function. 26828122 0 76 theme thiamine 18:25 arg1 hTPPT 54:58 hTPPT 54:58 hTPPT 54:58 The human colonic thiamine pyrophosphate transporter (hTPPT) is a glycoprotein and N-linked glycosylation is important for its function. 26828122 6 77 dep membrane 1361:1368 arg1 determined 1373:1382 determined 1373:1382 determined by live cell confocal imaging 1373:1412 However, only N-glycosylation at Asn(69), Asn(155), and Asn(393) appeared to be important for transporter functionality possibly through an effect on protein conformation and/or interaction with its ligand (but not through changes in expression at the cell membrane as determined by live cell confocal imaging). 26828122 5 78 dep mutagenesis 1026:1036 arg1 mean 1004:1007 mean 1004:1007 mean 1004:1007 Glycosylation of hTPPT was shown, by mean of site-directed mutagenesis, to occur at Asn(69), Asn(155), Asn(197), Asn(393), and Asn(416). 26828122 2 79 theme other 380:384 arg1 regions 386:392 other regions 380:392 other regions of the intestinal tract 380:416 The hTPPT is highly expressed in the colon, but not in other regions of the intestinal tract and is localized exclusively at the apical membrane domain of epithelia. 26828122 8 80 theme transmembrane 1737:1749 arg1 program 1770:1776 the TMHMM transmembrane helixes prediction program 1727:1776 the TMHMM transmembrane helixes prediction program 1727:1776 The results also provide an indirect support for a membrane topology for hTPPT with 10 transmembrane domains as predicted by the TMHMM transmembrane helixes prediction program. 26828122 1 81 theme microbiota-generated 276:295 arg1 TPP 297:299 the microbiota-generated TPP 272:299 the microbiota-generated TPP 272:299 The recently identified human thiamine pyrophosphate transporter (hTPPT; product of the SLC44A4 gene) is responsible for absorption of the microbiota-generated TPP in the large intestine. 26828122 6 82 theme transporter 1198:1208 arg1 functionality 1210:1222 transporter functionality 1198:1222 transporter functionality 1198:1222 However, only N-glycosylation at Asn(69), Asn(155), and Asn(393) appeared to be important for transporter functionality possibly through an effect on protein conformation and/or interaction with its ligand (but not through changes in expression at the cell membrane as determined by live cell confocal imaging). 26828122 3 83 theme sites 592:596 arg1 number 557:562 a number 555:562 a number of putative N-glycosylation sites 555:596 The hTPPT protein is predicted to have multiple TM domains with a number of putative N-glycosylation sites, but it is not known if the protein is actually glycosylated, and if so at which site, and their role in the functionality of the transporter. 26828122 1 84 dep transporter 190:200 arg1 hTPPT 203:207 hTPPT 203:207 hTPPT; product of the SLC44A4 gene 203:236 The recently identified human thiamine pyrophosphate transporter (hTPPT; product of the SLC44A4 gene) is responsible for absorption of the microbiota-generated TPP in the large intestine. 26828122 8 85 theme prediction 1759:1768 arg1 program 1770:1776 the TMHMM transmembrane helixes prediction program 1727:1776 the TMHMM transmembrane helixes prediction program 1727:1776 The results also provide an indirect support for a membrane topology for hTPPT with 10 transmembrane domains as predicted by the TMHMM transmembrane helixes prediction program. 26828122 1 86 theme large 308:312 arg1 intestine 314:322 the large intestine 304:322 the large intestine 304:322 The recently identified human thiamine pyrophosphate transporter (hTPPT; product of the SLC44A4 gene) is responsible for absorption of the microbiota-generated TPP in the large intestine. 26828122 0 87 link N-linked 83:90 arg1 glycosylation 92:104 N-linked glycosylation 83:104 N-linked glycosylation 83:104 The human colonic thiamine pyrophosphate transporter (hTPPT) is a glycoprotein and N-linked glycosylation is important for its function. 26828122 1 88 dep hTPPT 203:207 arg1 product 210:216 product 210:216 hTPPT; product of the SLC44A4 gene 203:236 The recently identified human thiamine pyrophosphate transporter (hTPPT; product of the SLC44A4 gene) is responsible for absorption of the microbiota-generated TPP in the large intestine. 26828122 1 89 theme gene 233:236 arg1 product 210:216 product 210:216 hTPPT; product of the SLC44A4 gene 203:236 The recently identified human thiamine pyrophosphate transporter (hTPPT; product of the SLC44A4 gene) is responsible for absorption of the microbiota-generated TPP in the large intestine. 26938549 0 0 theme Intracellular 70:82 arg1 Vesicles 98:105 Intracellular CD63-Positive Vesicles 70:105 Intracellular CD63-Positive Vesicles 70:105 Mutation of Glycosylation Sites in BST-2 Leads to Its Accumulation at Intracellular CD63-Positive Vesicles without Affecting Its Antiviral Activity against Multivesicular Body-Targeted HIV-1 and Hepatitis B Virus. 26938549 0 1 theme B 205:205 arg1 Virus 207:211 Hepatitis B Virus 195:211 Hepatitis B Virus 195:211 Mutation of Glycosylation Sites in BST-2 Leads to Its Accumulation at Intracellular CD63-Positive Vesicles without Affecting Its Antiviral Activity against Multivesicular Body-Targeted HIV-1 and Hepatitis B Virus. 26938549 4 2 theme BST-2 761:765 arg1 co-localization 742:756 the co-localization 738:756 the co-localization of BST-2 with EEA1 and LAMP1 738:785 BST-2 with this phenotype potently inhibited the release of multivesicular body-targeted HIV-1 and hepatitis B virus, without affecting the co-localization of BST-2 with EEA1 and LAMP1. 26938549 0 3 theme Hepatitis 195:203 arg1 Virus 207:211 Hepatitis B Virus 195:211 Hepatitis B Virus 195:211 Mutation of Glycosylation Sites in BST-2 Leads to Its Accumulation at Intracellular CD63-Positive Vesicles without Affecting Its Antiviral Activity against Multivesicular Body-Targeted HIV-1 and Hepatitis B Virus. 26938549 5 4 theme antiviral 1031:1039 arg1 function 1041:1048 the canonical antiviral function 1017:1048 the canonical antiviral function of BST-2 1017:1057 These results suggest that N-linked glycosylation of human BST-2 is dispensable for intracellular virion retention and imply that this recently discovered intracellular tethering function may be evolutionarily distinguished from the canonical antiviral function of BST-2 by tethering nascent virions at the cell surface. 26938549 0 5 from Mutation 0:7 arg1 BST-2 35:39 BST-2 35:39 BST-2 35:39 Mutation of Glycosylation Sites in BST-2 Leads to Its Accumulation at Intracellular CD63-Positive Vesicles without Affecting Its Antiviral Activity against Multivesicular Body-Targeted HIV-1 and Hepatitis B Virus. 26938549 3 6 theme CD63-positive 578:590 arg1 vesicles 592:599 intracellular CD63-positive vesicles 564:599 intracellular CD63-positive vesicles 564:599 Here, we confirmed that mutation of glycosylation sites exerted an effect of post-translational mis-trafficking, leading to an accumulation of BST-2 at intracellular CD63-positive vesicles. 26938549 3 7 from vesicles 592:599 arg1 accumulation 539:550 an accumulation 536:550 an accumulation of BST-2 at intracellular CD63-positive vesicles 536:599 Here, we confirmed that mutation of glycosylation sites exerted an effect of post-translational mis-trafficking, leading to an accumulation of BST-2 at intracellular CD63-positive vesicles. 26938549 0 8 theme CD63-Positive 84:96 arg1 Vesicles 98:105 Intracellular CD63-Positive Vesicles 70:105 Intracellular CD63-Positive Vesicles 70:105 Mutation of Glycosylation Sites in BST-2 Leads to Its Accumulation at Intracellular CD63-Positive Vesicles without Affecting Its Antiviral Activity against Multivesicular Body-Targeted HIV-1 and Hepatitis B Virus. 26938549 5 9 theme tethering 1062:1070 arg1 virions 1080:1086 tethering nascent virions 1062:1086 tethering nascent virions at the cell surface 1062:1106 These results suggest that N-linked glycosylation of human BST-2 is dispensable for intracellular virion retention and imply that this recently discovered intracellular tethering function may be evolutionarily distinguished from the canonical antiviral function of BST-2 by tethering nascent virions at the cell surface. 26938549 4 10 theme HIV-1 691:695 arg1 release 651:657 the release 647:657 the release of multivesicular body-targeted HIV-1 and hepatitis B virus 647:717 BST-2 with this phenotype potently inhibited the release of multivesicular body-targeted HIV-1 and hepatitis B virus, without affecting the co-localization of BST-2 with EEA1 and LAMP1. 26938549 4 11 with BST-2 602:606 arg1 phenotype 618:626 this phenotype 613:626 this phenotype 613:626 BST-2 with this phenotype potently inhibited the release of multivesicular body-targeted HIV-1 and hepatitis B virus, without affecting the co-localization of BST-2 with EEA1 and LAMP1. 26938549 5 12 from surface 1100:1106 arg1 virions 1080:1086 tethering nascent virions 1062:1086 tethering nascent virions at the cell surface 1062:1106 These results suggest that N-linked glycosylation of human BST-2 is dispensable for intracellular virion retention and imply that this recently discovered intracellular tethering function may be evolutionarily distinguished from the canonical antiviral function of BST-2 by tethering nascent virions at the cell surface. 26938549 3 13 theme sites 462:466 arg1 mutation 436:443 mutation 436:443 mutation of glycosylation sites 436:466 Here, we confirmed that mutation of glycosylation sites exerted an effect of post-translational mis-trafficking, leading to an accumulation of BST-2 at intracellular CD63-positive vesicles. 26938549 4 14 with co-localization 742:756 arg1 EEA1 772:775 EEA1 772:775 EEA1 772:775 BST-2 with this phenotype potently inhibited the release of multivesicular body-targeted HIV-1 and hepatitis B virus, without affecting the co-localization of BST-2 with EEA1 and LAMP1. 26938549 4 14 with co-localization 742:756 arg1 LAMP1 781:785 LAMP1 781:785 LAMP1 781:785 BST-2 with this phenotype potently inhibited the release of multivesicular body-targeted HIV-1 and hepatitis B virus, without affecting the co-localization of BST-2 with EEA1 and LAMP1. 26938549 3 15 theme intracellular 564:576 arg1 vesicles 592:599 intracellular CD63-positive vesicles 564:599 intracellular CD63-positive vesicles 564:599 Here, we confirmed that mutation of glycosylation sites exerted an effect of post-translational mis-trafficking, leading to an accumulation of BST-2 at intracellular CD63-positive vesicles. 26938549 4 16 theme virus 713:717 arg1 release 651:657 the release 647:657 the release of multivesicular body-targeted HIV-1 and hepatitis B virus 647:717 BST-2 with this phenotype potently inhibited the release of multivesicular body-targeted HIV-1 and hepatitis B virus, without affecting the co-localization of BST-2 with EEA1 and LAMP1. 26938549 5 17 theme cell 1095:1098 arg1 surface 1100:1106 the cell surface 1091:1106 the cell surface 1091:1106 These results suggest that N-linked glycosylation of human BST-2 is dispensable for intracellular virion retention and imply that this recently discovered intracellular tethering function may be evolutionarily distinguished from the canonical antiviral function of BST-2 by tethering nascent virions at the cell surface. 26938549 2 18 theme detailed 332:339 arg1 contribution 341:352 The detailed contribution 328:352 The detailed contribution of N-linked glycosylation to this model 328:392 The detailed contribution of N-linked glycosylation to this model is controversial. 26938549 2 18 theme detailed 332:339 arg1 controversial 397:409 controversial 397:409 controversial 397:409 The detailed contribution of N-linked glycosylation to this model is controversial. 26938549 5 19 theme intracellular 943:955 arg1 function 967:974 this recently discovered intracellular tethering function 918:974 this recently discovered intracellular tethering function 918:974 These results suggest that N-linked glycosylation of human BST-2 is dispensable for intracellular virion retention and imply that this recently discovered intracellular tethering function may be evolutionarily distinguished from the canonical antiviral function of BST-2 by tethering nascent virions at the cell surface. 26938549 5 20 theme intracellular 872:884 arg1 retention 893:901 intracellular virion retention 872:901 intracellular virion retention 872:901 These results suggest that N-linked glycosylation of human BST-2 is dispensable for intracellular virion retention and imply that this recently discovered intracellular tethering function may be evolutionarily distinguished from the canonical antiviral function of BST-2 by tethering nascent virions at the cell surface. 26938549 3 21 theme glycosylation 448:460 arg1 sites 462:466 glycosylation sites 448:466 glycosylation sites 448:466 Here, we confirmed that mutation of glycosylation sites exerted an effect of post-translational mis-trafficking, leading to an accumulation of BST-2 at intracellular CD63-positive vesicles. 26938549 0 22 theme Sites 26:30 arg1 Mutation 0:7 Mutation 0:7 Mutation of Glycosylation Sites in BST-2 0:39 Mutation of Glycosylation Sites in BST-2 Leads to Its Accumulation at Intracellular CD63-Positive Vesicles without Affecting Its Antiviral Activity against Multivesicular Body-Targeted HIV-1 and Hepatitis B Virus. 26938549 1 23 theme physical 301:308 arg1 model 321:325 a "physical tethering" model 298:325 a "physical tethering" model 298:325 BST-2/tetherin blocks the release of various enveloped viruses including HIV-1 with a "physical tethering" model. 26938549 0 24 theme Antiviral 129:137 arg1 Activity 139:146 Its Antiviral Activity 125:146 Its Antiviral Activity against Multivesicular Body-Targeted HIV-1 and Hepatitis B Virus 125:211 Mutation of Glycosylation Sites in BST-2 Leads to Its Accumulation at Intracellular CD63-Positive Vesicles without Affecting Its Antiviral Activity against Multivesicular Body-Targeted HIV-1 and Hepatitis B Virus. 26938549 0 25 theme Glycosylation 12:24 arg1 Sites 26:30 Glycosylation Sites 12:30 Glycosylation Sites 12:30 Mutation of Glycosylation Sites in BST-2 Leads to Its Accumulation at Intracellular CD63-Positive Vesicles without Affecting Its Antiviral Activity against Multivesicular Body-Targeted HIV-1 and Hepatitis B Virus. 26938549 1 26 theme tethering 310:318 arg1 model 321:325 a "physical tethering" model 298:325 a "physical tethering" model 298:325 BST-2/tetherin blocks the release of various enveloped viruses including HIV-1 with a "physical tethering" model. 26938549 5 27 theme nascent 1072:1078 arg1 virions 1080:1086 tethering nascent virions 1062:1086 tethering nascent virions at the cell surface 1062:1106 These results suggest that N-linked glycosylation of human BST-2 is dispensable for intracellular virion retention and imply that this recently discovered intracellular tethering function may be evolutionarily distinguished from the canonical antiviral function of BST-2 by tethering nascent virions at the cell surface. 26938549 5 28 link N-linked 815:822 arg1 glycosylation 824:836 N-linked glycosylation 815:836 N-linked glycosylation of human BST-2 815:851 These results suggest that N-linked glycosylation of human BST-2 is dispensable for intracellular virion retention and imply that this recently discovered intracellular tethering function may be evolutionarily distinguished from the canonical antiviral function of BST-2 by tethering nascent virions at the cell surface. 26938549 3 29 theme post-translational 489:506 arg1 mis-trafficking 508:522 post-translational mis-trafficking 489:522 post-translational mis-trafficking 489:522 Here, we confirmed that mutation of glycosylation sites exerted an effect of post-translational mis-trafficking, leading to an accumulation of BST-2 at intracellular CD63-positive vesicles. 26938549 5 30 theme human 841:845 arg1 BST-2 847:851 human BST-2 841:851 human BST-2 841:851 These results suggest that N-linked glycosylation of human BST-2 is dispensable for intracellular virion retention and imply that this recently discovered intracellular tethering function may be evolutionarily distinguished from the canonical antiviral function of BST-2 by tethering nascent virions at the cell surface. 26938549 1 31 theme " 319:319 arg1 model 321:325 a "physical tethering" model 298:325 a "physical tethering" model 298:325 BST-2/tetherin blocks the release of various enveloped viruses including HIV-1 with a "physical tethering" model. 26938549 5 32 theme tethering 957:965 arg1 function 967:974 this recently discovered intracellular tethering function 918:974 this recently discovered intracellular tethering function 918:974 These results suggest that N-linked glycosylation of human BST-2 is dispensable for intracellular virion retention and imply that this recently discovered intracellular tethering function may be evolutionarily distinguished from the canonical antiviral function of BST-2 by tethering nascent virions at the cell surface. 26938549 4 33 theme B 711:711 arg1 virus 713:717 hepatitis B virus 701:717 hepatitis B virus 701:717 BST-2 with this phenotype potently inhibited the release of multivesicular body-targeted HIV-1 and hepatitis B virus, without affecting the co-localization of BST-2 with EEA1 and LAMP1. 26938549 5 34 theme BST-2 847:851 arg1 glycosylation 824:836 N-linked glycosylation 815:836 N-linked glycosylation of human BST-2 815:851 These results suggest that N-linked glycosylation of human BST-2 is dispensable for intracellular virion retention and imply that this recently discovered intracellular tethering function may be evolutionarily distinguished from the canonical antiviral function of BST-2 by tethering nascent virions at the cell surface. 26938549 4 35 theme body-targeted 677:689 arg1 HIV-1 691:695 multivesicular body-targeted HIV-1 662:695 multivesicular body-targeted HIV-1 662:695 BST-2 with this phenotype potently inhibited the release of multivesicular body-targeted HIV-1 and hepatitis B virus, without affecting the co-localization of BST-2 with EEA1 and LAMP1. 26938549 4 36 theme hepatitis 701:709 arg1 virus 713:717 hepatitis B virus 701:717 hepatitis B virus 701:717 BST-2 with this phenotype potently inhibited the release of multivesicular body-targeted HIV-1 and hepatitis B virus, without affecting the co-localization of BST-2 with EEA1 and LAMP1. 26938549 0 37 theme Body-Targeted 171:183 arg1 HIV-1 185:189 Multivesicular Body-Targeted HIV-1 156:189 Multivesicular Body-Targeted HIV-1 156:189 Mutation of Glycosylation Sites in BST-2 Leads to Its Accumulation at Intracellular CD63-Positive Vesicles without Affecting Its Antiviral Activity against Multivesicular Body-Targeted HIV-1 and Hepatitis B Virus. 26938549 2 38 theme glycosylation 366:378 arg1 contribution 341:352 The detailed contribution 328:352 The detailed contribution of N-linked glycosylation to this model 328:392 The detailed contribution of N-linked glycosylation to this model is controversial. 26938549 2 38 theme glycosylation 366:378 arg1 controversial 397:409 controversial 397:409 controversial 397:409 The detailed contribution of N-linked glycosylation to this model is controversial. 26938549 2 39 link N-linked 357:364 arg1 glycosylation 366:378 N-linked glycosylation 357:378 N-linked glycosylation 357:378 The detailed contribution of N-linked glycosylation to this model is controversial. 26938549 0 40 theme Multivesicular 156:169 arg1 HIV-1 185:189 Multivesicular Body-Targeted HIV-1 156:189 Multivesicular Body-Targeted HIV-1 156:189 Mutation of Glycosylation Sites in BST-2 Leads to Its Accumulation at Intracellular CD63-Positive Vesicles without Affecting Its Antiviral Activity against Multivesicular Body-Targeted HIV-1 and Hepatitis B Virus. 26938549 5 41 theme virion 886:891 arg1 retention 893:901 intracellular virion retention 872:901 intracellular virion retention 872:901 These results suggest that N-linked glycosylation of human BST-2 is dispensable for intracellular virion retention and imply that this recently discovered intracellular tethering function may be evolutionarily distinguished from the canonical antiviral function of BST-2 by tethering nascent virions at the cell surface. 26938549 2 42 theme N-linked 357:364 arg1 glycosylation 366:378 N-linked glycosylation 357:378 N-linked glycosylation 357:378 The detailed contribution of N-linked glycosylation to this model is controversial. 26938549 3 43 theme mis-trafficking 508:522 arg1 effect 479:484 an effect 476:484 an effect of post-translational mis-trafficking 476:522 Here, we confirmed that mutation of glycosylation sites exerted an effect of post-translational mis-trafficking, leading to an accumulation of BST-2 at intracellular CD63-positive vesicles. 26938549 5 44 gly glycosylation 824:836 arg1 BST-2 847:851 human BST-2 841:851 human BST-2 841:851 These results suggest that N-linked glycosylation of human BST-2 is dispensable for intracellular virion retention and imply that this recently discovered intracellular tethering function may be evolutionarily distinguished from the canonical antiviral function of BST-2 by tethering nascent virions at the cell surface. 26938549 0 45 from Vesicles 98:105 arg1 Accumulation 54:65 Its Accumulation 50:65 Its Accumulation at Intracellular CD63-Positive Vesicles 50:105 Mutation of Glycosylation Sites in BST-2 Leads to Its Accumulation at Intracellular CD63-Positive Vesicles without Affecting Its Antiviral Activity against Multivesicular Body-Targeted HIV-1 and Hepatitis B Virus. 26938549 5 46 theme canonical 1021:1029 arg1 function 1041:1048 the canonical antiviral function 1017:1048 the canonical antiviral function of BST-2 1017:1057 These results suggest that N-linked glycosylation of human BST-2 is dispensable for intracellular virion retention and imply that this recently discovered intracellular tethering function may be evolutionarily distinguished from the canonical antiviral function of BST-2 by tethering nascent virions at the cell surface. 26938549 1 47 theme various 251:257 arg1 HIV-1 287:291 HIV-1 287:291 HIV-1 287:291 BST-2/tetherin blocks the release of various enveloped viruses including HIV-1 with a "physical tethering" model. 26938549 1 47 theme various 251:257 arg1 viruses 269:275 various enveloped viruses 251:275 various enveloped viruses including HIV-1 with a "physical tethering" model 251:325 BST-2/tetherin blocks the release of various enveloped viruses including HIV-1 with a "physical tethering" model. 26938549 3 48 gly glycosylation 448:460 arg2 sites 462:466 glycosylation sites 448:466 glycosylation sites 448:466 Here, we confirmed that mutation of glycosylation sites exerted an effect of post-translational mis-trafficking, leading to an accumulation of BST-2 at intracellular CD63-positive vesicles. 26938549 1 49 with viruses 269:275 arg1 model 321:325 a "physical tethering" model 298:325 a "physical tethering" model 298:325 BST-2/tetherin blocks the release of various enveloped viruses including HIV-1 with a "physical tethering" model. 26938549 5 50 theme BST-2 1053:1057 arg1 function 1041:1048 the canonical antiviral function 1017:1048 the canonical antiviral function of BST-2 1017:1057 These results suggest that N-linked glycosylation of human BST-2 is dispensable for intracellular virion retention and imply that this recently discovered intracellular tethering function may be evolutionarily distinguished from the canonical antiviral function of BST-2 by tethering nascent virions at the cell surface. 26938549 5 51 theme discovered 932:941 arg1 function 967:974 this recently discovered intracellular tethering function 918:974 this recently discovered intracellular tethering function 918:974 These results suggest that N-linked glycosylation of human BST-2 is dispensable for intracellular virion retention and imply that this recently discovered intracellular tethering function may be evolutionarily distinguished from the canonical antiviral function of BST-2 by tethering nascent virions at the cell surface. 26938549 1 52 theme enveloped 259:267 arg1 HIV-1 287:291 HIV-1 287:291 HIV-1 287:291 BST-2/tetherin blocks the release of various enveloped viruses including HIV-1 with a "physical tethering" model. 26938549 1 52 theme enveloped 259:267 arg1 viruses 269:275 various enveloped viruses 251:275 various enveloped viruses including HIV-1 with a "physical tethering" model 251:325 BST-2/tetherin blocks the release of various enveloped viruses including HIV-1 with a "physical tethering" model. 26938549 5 53 theme N-linked 815:822 arg1 glycosylation 824:836 N-linked glycosylation 815:836 N-linked glycosylation of human BST-2 815:851 These results suggest that N-linked glycosylation of human BST-2 is dispensable for intracellular virion retention and imply that this recently discovered intracellular tethering function may be evolutionarily distinguished from the canonical antiviral function of BST-2 by tethering nascent virions at the cell surface. 26938549 4 54 theme multivesicular 662:675 arg1 HIV-1 691:695 multivesicular body-targeted HIV-1 662:695 multivesicular body-targeted HIV-1 662:695 BST-2 with this phenotype potently inhibited the release of multivesicular body-targeted HIV-1 and hepatitis B virus, without affecting the co-localization of BST-2 with EEA1 and LAMP1. 26938549 3 55 theme BST-2 555:559 arg1 accumulation 539:550 an accumulation 536:550 an accumulation of BST-2 at intracellular CD63-positive vesicles 536:599 Here, we confirmed that mutation of glycosylation sites exerted an effect of post-translational mis-trafficking, leading to an accumulation of BST-2 at intracellular CD63-positive vesicles. 26938549 1 56 theme viruses 269:275 arg1 release 240:246 the release 236:246 the release of various enveloped viruses including HIV-1 with a "physical tethering" model 236:325 BST-2/tetherin blocks the release of various enveloped viruses including HIV-1 with a "physical tethering" model. 24719335 6 0 theme chemical 951:958 arg1 inhibition 960:969 chemical inhibition 951:969 chemical inhibition of lysosomal degradation 951:994 Wild-type and N-glycosylation-deficient TRPP2 is degraded in lysosomes, as shown by increased TRPP2 protein levels upon chemical inhibition of lysosomal degradation. 24719335 6 1 theme N-glycosylation-deficient 845:869 arg1 TRPP2 871:875 Wild-type and N-glycosylation-deficient TRPP2 831:875 Wild-type and N-glycosylation-deficient TRPP2 831:875 Wild-type and N-glycosylation-deficient TRPP2 is degraded in lysosomes, as shown by increased TRPP2 protein levels upon chemical inhibition of lysosomal degradation. 24719335 10 2 theme glycan 1598:1603 arg1 trimming 1605:1612 GII-mediated glycan trimming 1585:1612 GII-mediated glycan trimming 1585:1612 These results highlight the biological importance of N-linked glycosylation and GII-mediated glycan trimming in the control of biogenesis and stability of TRPP2. 24719335 6 3 theme Wild-type 831:839 arg1 TRPP2 871:875 Wild-type and N-glycosylation-deficient TRPP2 831:875 Wild-type and N-glycosylation-deficient TRPP2 831:875 Wild-type and N-glycosylation-deficient TRPP2 is degraded in lysosomes, as shown by increased TRPP2 protein levels upon chemical inhibition of lysosomal degradation. 24719335 2 4 theme polycystic 295:304 arg1 disease 313:319 autosomal dominant polycystic kidney disease 276:319 autosomal dominant polycystic kidney disease 276:319 Transient receptor potential channel TRPP2 is a nonselective cation channel that is mutated in autosomal dominant polycystic kidney disease. 24719335 6 5 theme TRPP2 925:929 arg1 levels 939:944 increased TRPP2 protein levels 915:944 increased TRPP2 protein levels upon chemical inhibition of lysosomal degradation 915:994 Wild-type and N-glycosylation-deficient TRPP2 is degraded in lysosomes, as shown by increased TRPP2 protein levels upon chemical inhibition of lysosomal degradation. 24719335 3 6 link N-linked 428:435 arg1 glycosylation 437:449 N-linked glycosylation 428:449 N-linked glycosylation 428:449 TRPP2 has been shown to be heavily N-glycosylated, but the glycosylation sites and the biological role of N-linked glycosylation have not been investigated. 24719335 8 7 theme polycystic 1251:1260 arg1 ADPLD 1277:1281 ADPLD 1277:1281 ADPLD 1277:1281 The non-catalytic β subunit of glucosidase II (GIIβ) is encoded by PRKCSH, one of the genes causing autosomal dominant polycystic liver disease (ADPLD). 24719335 8 7 theme polycystic 1251:1260 arg1 disease 1268:1274 autosomal dominant polycystic liver disease 1232:1274 autosomal dominant polycystic liver disease (ADPLD) 1232:1282 The non-catalytic β subunit of glucosidase II (GIIβ) is encoded by PRKCSH, one of the genes causing autosomal dominant polycystic liver disease (ADPLD). 24719335 2 8 theme autosomal 276:284 arg1 disease 313:319 autosomal dominant polycystic kidney disease 276:319 autosomal dominant polycystic kidney disease 276:319 Transient receptor potential channel TRPP2 is a nonselective cation channel that is mutated in autosomal dominant polycystic kidney disease. 24719335 9 9 theme genetic 1441:1447 arg1 interaction 1449:1459 the genetic interaction 1437:1459 the genetic interaction observed between TRPP2 and PRKCSH in ADPLD 1437:1502 The impaired GIIβ-dependent glucose trimming of TRPP2 glycosylation in ADPLD may explain the decreased TRPP2 protein expression in Prkcsh(-/-) mice and the genetic interaction observed between TRPP2 and PRKCSH in ADPLD. 24719335 7 10 theme TRPP2 1125:1129 arg1 trimming 1113:1120 glycan trimming 1106:1120 glycan trimming of TRPP2 1106:1129 In addition, using pharmacological and genetic approaches, we demonstrate that glucosidase II (GII) mediates glycan trimming of TRPP2. 24719335 9 11 from trimming 1321:1328 arg1 ADPLD 1356:1360 ADPLD 1356:1360 ADPLD 1356:1360 The impaired GIIβ-dependent glucose trimming of TRPP2 glycosylation in ADPLD may explain the decreased TRPP2 protein expression in Prkcsh(-/-) mice and the genetic interaction observed between TRPP2 and PRKCSH in ADPLD. 24719335 8 12 theme genes 1218:1222 arg1 one 1207:1209 one 1207:1209 one 1207:1209 The non-catalytic β subunit of glucosidase II (GIIβ) is encoded by PRKCSH, one of the genes causing autosomal dominant polycystic liver disease (ADPLD). 24719335 8 12 theme genes 1218:1222 arg1 genes 1218:1222 the genes 1214:1222 the genes causing autosomal dominant polycystic liver disease (ADPLD) 1214:1282 The non-catalytic β subunit of glucosidase II (GIIβ) is encoded by PRKCSH, one of the genes causing autosomal dominant polycystic liver disease (ADPLD). 24719335 8 12 theme genes 1218:1222 arg1 PRKCSH 1199:1204 PRKCSH 1199:1204 PRKCSH 1199:1204 The non-catalytic β subunit of glucosidase II (GIIβ) is encoded by PRKCSH, one of the genes causing autosomal dominant polycystic liver disease (ADPLD). 24719335 10 13 theme TRPP2 1660:1664 arg1 stability 1647:1655 stability 1647:1655 stability 1647:1655 These results highlight the biological importance of N-linked glycosylation and GII-mediated glycan trimming in the control of biogenesis and stability of TRPP2. 24719335 10 13 theme TRPP2 1660:1664 arg1 biogenesis 1632:1641 biogenesis 1632:1641 biogenesis 1632:1641 These results highlight the biological importance of N-linked glycosylation and GII-mediated glycan trimming in the control of biogenesis and stability of TRPP2. 24719335 10 14 theme stability 1647:1655 arg1 control 1621:1627 the control 1617:1627 the control of biogenesis and stability of TRPP2 1617:1664 These results highlight the biological importance of N-linked glycosylation and GII-mediated glycan trimming in the control of biogenesis and stability of TRPP2. 24719335 2 15 theme cation 242:247 arg1 channel 249:255 a nonselective cation channel 227:255 a nonselective cation channel that is mutated in autosomal dominant polycystic kidney disease 227:319 Transient receptor potential channel TRPP2 is a nonselective cation channel that is mutated in autosomal dominant polycystic kidney disease. 24719335 2 15 theme cation 242:247 arg1 TRPP2 218:222 Transient receptor potential channel TRPP2 181:222 Transient receptor potential channel TRPP2 181:222 Transient receptor potential channel TRPP2 is a nonselective cation channel that is mutated in autosomal dominant polycystic kidney disease. 24719335 8 16 theme autosomal 1232:1240 arg1 ADPLD 1277:1281 ADPLD 1277:1281 ADPLD 1277:1281 The non-catalytic β subunit of glucosidase II (GIIβ) is encoded by PRKCSH, one of the genes causing autosomal dominant polycystic liver disease (ADPLD). 24719335 8 16 theme autosomal 1232:1240 arg1 disease 1268:1274 autosomal dominant polycystic liver disease 1232:1274 autosomal dominant polycystic liver disease (ADPLD) 1232:1282 The non-catalytic β subunit of glucosidase II (GIIβ) is encoded by PRKCSH, one of the genes causing autosomal dominant polycystic liver disease (ADPLD). 24719335 6 17 theme degradation 984:994 arg1 inhibition 960:969 chemical inhibition 951:969 chemical inhibition of lysosomal degradation 951:994 Wild-type and N-glycosylation-deficient TRPP2 is degraded in lysosomes, as shown by increased TRPP2 protein levels upon chemical inhibition of lysosomal degradation. 24719335 10 18 theme biogenesis 1632:1641 arg1 control 1621:1627 the control 1617:1627 the control of biogenesis and stability of TRPP2 1617:1664 These results highlight the biological importance of N-linked glycosylation and GII-mediated glycan trimming in the control of biogenesis and stability of TRPP2. 24719335 5 19 theme TRPP2 707:711 arg1 biogenesis 693:702 the efficient biogenesis 679:702 the efficient biogenesis of TRPP2 679:711 Glycosylation is required for the efficient biogenesis of TRPP2 because mutations of the glycosylated asparagines result in strongly decreased protein expression of the ion channel. 24719335 7 20 theme genetic 1036:1042 arg1 approaches 1044:1053 pharmacological and genetic approaches 1016:1053 pharmacological and genetic approaches 1016:1053 In addition, using pharmacological and genetic approaches, we demonstrate that glucosidase II (GII) mediates glycan trimming of TRPP2. 24719335 5 21 theme decreased 782:790 arg1 expression 800:809 strongly decreased protein expression 773:809 strongly decreased protein expression of the ion channel 773:828 Glycosylation is required for the efficient biogenesis of TRPP2 because mutations of the glycosylated asparagines result in strongly decreased protein expression of the ion channel. 24719335 7 22 theme pharmacological 1016:1030 arg1 approaches 1044:1053 pharmacological and genetic approaches 1016:1053 pharmacological and genetic approaches 1016:1053 In addition, using pharmacological and genetic approaches, we demonstrate that glucosidase II (GII) mediates glycan trimming of TRPP2. 24719335 0 23 theme TRPP2 85:89 arg1 abundance 31:39 the abundance 27:39 the abundance of the transient receptor potential channel TRPP2 27:89 N-glycosylation determines the abundance of the transient receptor potential channel TRPP2. 24719335 9 24 theme GIIβ-dependent 1298:1311 arg1 trimming 1321:1328 The impaired GIIβ-dependent glucose trimming 1285:1328 The impaired GIIβ-dependent glucose trimming of TRPP2 glycosylation in ADPLD 1285:1360 The impaired GIIβ-dependent glucose trimming of TRPP2 glycosylation in ADPLD may explain the decreased TRPP2 protein expression in Prkcsh(-/-) mice and the genetic interaction observed between TRPP2 and PRKCSH in ADPLD. 24719335 1 25 theme membrane 162:169 arg1 proteins 171:178 membrane proteins 162:178 membrane proteins 162:178 Glycosylation plays a critical role in the biogenesis and function of membrane proteins. 24719335 5 26 theme asparagines 751:761 arg1 mutations 721:729 mutations 721:729 mutations of the glycosylated asparagines 721:761 Glycosylation is required for the efficient biogenesis of TRPP2 because mutations of the glycosylated asparagines result in strongly decreased protein expression of the ion channel. 24719335 0 27 theme receptor 58:65 arg1 TRPP2 85:89 the transient receptor potential channel TRPP2 44:89 the transient receptor potential channel TRPP2 44:89 N-glycosylation determines the abundance of the transient receptor potential channel TRPP2. 24719335 9 28 theme TRPP2 1333:1337 arg1 glycosylation 1339:1351 TRPP2 glycosylation 1333:1351 TRPP2 glycosylation 1333:1351 The impaired GIIβ-dependent glucose trimming of TRPP2 glycosylation in ADPLD may explain the decreased TRPP2 protein expression in Prkcsh(-/-) mice and the genetic interaction observed between TRPP2 and PRKCSH in ADPLD. 24719335 3 29 theme N-linked 428:435 arg1 glycosylation 437:449 N-linked glycosylation 428:449 N-linked glycosylation 428:449 TRPP2 has been shown to be heavily N-glycosylated, but the glycosylation sites and the biological role of N-linked glycosylation have not been investigated. 24719335 1 30 theme critical 114:121 arg1 role 123:126 a critical role 112:126 a critical role 112:126 Glycosylation plays a critical role in the biogenesis and function of membrane proteins. 24719335 4 31 theme native 567:572 arg1 TRPP2 574:578 native TRPP2 567:578 native TRPP2 567:578 Here we show, using a combination of mass spectrometry and biochemical approaches, that native TRPP2 is glycosylated at five asparagines in the first extracellular loop. 24719335 2 32 theme Transient 181:189 arg1 channel 249:255 a nonselective cation channel 227:255 a nonselective cation channel that is mutated in autosomal dominant polycystic kidney disease 227:319 Transient receptor potential channel TRPP2 is a nonselective cation channel that is mutated in autosomal dominant polycystic kidney disease. 24719335 2 32 theme Transient 181:189 arg1 TRPP2 218:222 Transient receptor potential channel TRPP2 181:222 Transient receptor potential channel TRPP2 181:222 Transient receptor potential channel TRPP2 is a nonselective cation channel that is mutated in autosomal dominant polycystic kidney disease. 24719335 4 33 theme spectrometry 521:532 arg1 combination 501:511 a combination 499:511 a combination of mass spectrometry and biochemical approaches 499:559 Here we show, using a combination of mass spectrometry and biochemical approaches, that native TRPP2 is glycosylated at five asparagines in the first extracellular loop. 24719335 10 34 theme biological 1533:1542 arg1 importance 1544:1553 the biological importance 1529:1553 the biological importance of N-linked glycosylation and GII-mediated glycan trimming in the control of biogenesis and stability of TRPP2 1529:1664 These results highlight the biological importance of N-linked glycosylation and GII-mediated glycan trimming in the control of biogenesis and stability of TRPP2. 24719335 0 35 theme potential 67:75 arg1 TRPP2 85:89 the transient receptor potential channel TRPP2 44:89 the transient receptor potential channel TRPP2 44:89 N-glycosylation determines the abundance of the transient receptor potential channel TRPP2. 24719335 5 36 theme channel 822:828 arg1 expression 800:809 strongly decreased protein expression 773:809 strongly decreased protein expression of the ion channel 773:828 Glycosylation is required for the efficient biogenesis of TRPP2 because mutations of the glycosylated asparagines result in strongly decreased protein expression of the ion channel. 24719335 9 37 theme TRPP2 1388:1392 arg1 expression 1402:1411 the decreased TRPP2 protein expression 1374:1411 the decreased TRPP2 protein expression in Prkcsh(-/-) mice 1374:1431 The impaired GIIβ-dependent glucose trimming of TRPP2 glycosylation in ADPLD may explain the decreased TRPP2 protein expression in Prkcsh(-/-) mice and the genetic interaction observed between TRPP2 and PRKCSH in ADPLD. 24719335 8 38 theme non-catalytic 1136:1148 arg1 GIIβ 1179:1182 GIIβ 1179:1182 GIIβ 1179:1182 The non-catalytic β subunit of glucosidase II (GIIβ) is encoded by PRKCSH, one of the genes causing autosomal dominant polycystic liver disease (ADPLD). 24719335 8 38 theme non-catalytic 1136:1148 arg1 subunit 1152:1158 The non-catalytic β subunit 1132:1158 The non-catalytic β subunit of glucosidase II (GIIβ) 1132:1183 The non-catalytic β subunit of glucosidase II (GIIβ) is encoded by PRKCSH, one of the genes causing autosomal dominant polycystic liver disease (ADPLD). 24719335 4 39 theme biochemical 538:548 arg1 approaches 550:559 biochemical approaches 538:559 biochemical approaches 538:559 Here we show, using a combination of mass spectrometry and biochemical approaches, that native TRPP2 is glycosylated at five asparagines in the first extracellular loop. 24719335 10 40 link N-linked 1558:1565 arg1 glycosylation 1567:1579 N-linked glycosylation 1558:1579 N-linked glycosylation 1558:1579 These results highlight the biological importance of N-linked glycosylation and GII-mediated glycan trimming in the control of biogenesis and stability of TRPP2. 24719335 9 41 from interaction 1449:1459 arg1 mice 1428:1431 Prkcsh(-/-) mice 1416:1431 Prkcsh(-/-) mice 1416:1431 The impaired GIIβ-dependent glucose trimming of TRPP2 glycosylation in ADPLD may explain the decreased TRPP2 protein expression in Prkcsh(-/-) mice and the genetic interaction observed between TRPP2 and PRKCSH in ADPLD. 24719335 10 42 theme glycosylation 1567:1579 arg1 importance 1544:1553 the biological importance 1529:1553 the biological importance of N-linked glycosylation and GII-mediated glycan trimming in the control of biogenesis and stability of TRPP2 1529:1664 These results highlight the biological importance of N-linked glycosylation and GII-mediated glycan trimming in the control of biogenesis and stability of TRPP2. 24719335 2 43 theme potential 200:208 arg1 channel 249:255 a nonselective cation channel 227:255 a nonselective cation channel that is mutated in autosomal dominant polycystic kidney disease 227:319 Transient receptor potential channel TRPP2 is a nonselective cation channel that is mutated in autosomal dominant polycystic kidney disease. 24719335 2 43 theme potential 200:208 arg1 TRPP2 218:222 Transient receptor potential channel TRPP2 181:222 Transient receptor potential channel TRPP2 181:222 Transient receptor potential channel TRPP2 is a nonselective cation channel that is mutated in autosomal dominant polycystic kidney disease. 24719335 3 44 gly glycosylation 437:449 arg2 glycosylation 437:449 N-linked glycosylation 428:449 N-linked glycosylation 428:449 TRPP2 has been shown to be heavily N-glycosylated, but the glycosylation sites and the biological role of N-linked glycosylation have not been investigated. 24719335 3 44 gly glycosylation 437:449 arg2 sites 395:399 the glycosylation sites 377:399 the glycosylation sites 377:399 TRPP2 has been shown to be heavily N-glycosylated, but the glycosylation sites and the biological role of N-linked glycosylation have not been investigated. 24719335 9 45 theme Prkcsh 1416:1421 arg1 mice 1428:1431 Prkcsh(-/-) mice 1416:1431 Prkcsh(-/-) mice 1416:1431 The impaired GIIβ-dependent glucose trimming of TRPP2 glycosylation in ADPLD may explain the decreased TRPP2 protein expression in Prkcsh(-/-) mice and the genetic interaction observed between TRPP2 and PRKCSH in ADPLD. 24719335 8 46 theme glucosidase 1163:1173 arg1 GIIβ 1179:1182 GIIβ 1179:1182 GIIβ 1179:1182 The non-catalytic β subunit of glucosidase II (GIIβ) is encoded by PRKCSH, one of the genes causing autosomal dominant polycystic liver disease (ADPLD). 24719335 8 46 theme glucosidase 1163:1173 arg1 subunit 1152:1158 The non-catalytic β subunit 1132:1158 The non-catalytic β subunit of glucosidase II (GIIβ) 1132:1183 The non-catalytic β subunit of glucosidase II (GIIβ) is encoded by PRKCSH, one of the genes causing autosomal dominant polycystic liver disease (ADPLD). 24719335 9 47 theme -/- 1423:1425 arg1 mice 1428:1431 Prkcsh(-/-) mice 1416:1431 Prkcsh(-/-) mice 1416:1431 The impaired GIIβ-dependent glucose trimming of TRPP2 glycosylation in ADPLD may explain the decreased TRPP2 protein expression in Prkcsh(-/-) mice and the genetic interaction observed between TRPP2 and PRKCSH in ADPLD. 24719335 10 48 theme trimming 1605:1612 arg1 importance 1544:1553 the biological importance 1529:1553 the biological importance of N-linked glycosylation and GII-mediated glycan trimming in the control of biogenesis and stability of TRPP2 1529:1664 These results highlight the biological importance of N-linked glycosylation and GII-mediated glycan trimming in the control of biogenesis and stability of TRPP2. 24719335 2 49 theme kidney 306:311 arg1 disease 313:319 autosomal dominant polycystic kidney disease 276:319 autosomal dominant polycystic kidney disease 276:319 Transient receptor potential channel TRPP2 is a nonselective cation channel that is mutated in autosomal dominant polycystic kidney disease. 24719335 6 50 theme protein 931:937 arg1 levels 939:944 increased TRPP2 protein levels 915:944 increased TRPP2 protein levels upon chemical inhibition of lysosomal degradation 915:994 Wild-type and N-glycosylation-deficient TRPP2 is degraded in lysosomes, as shown by increased TRPP2 protein levels upon chemical inhibition of lysosomal degradation. 24719335 10 51 theme GII-mediated 1585:1596 arg1 trimming 1605:1612 GII-mediated glycan trimming 1585:1612 GII-mediated glycan trimming 1585:1612 These results highlight the biological importance of N-linked glycosylation and GII-mediated glycan trimming in the control of biogenesis and stability of TRPP2. 24719335 2 52 theme dominant 286:293 arg1 disease 313:319 autosomal dominant polycystic kidney disease 276:319 autosomal dominant polycystic kidney disease 276:319 Transient receptor potential channel TRPP2 is a nonselective cation channel that is mutated in autosomal dominant polycystic kidney disease. 24719335 1 53 theme proteins 171:178 arg1 function 150:157 function 150:157 function 150:157 Glycosylation plays a critical role in the biogenesis and function of membrane proteins. 24719335 1 53 theme proteins 171:178 arg1 biogenesis 135:144 biogenesis 135:144 biogenesis 135:144 Glycosylation plays a critical role in the biogenesis and function of membrane proteins. 24719335 0 54 theme transient 48:56 arg1 TRPP2 85:89 the transient receptor potential channel TRPP2 44:89 the transient receptor potential channel TRPP2 44:89 N-glycosylation determines the abundance of the transient receptor potential channel TRPP2. 24719335 6 55 theme increased 915:923 arg1 levels 939:944 increased TRPP2 protein levels 915:944 increased TRPP2 protein levels upon chemical inhibition of lysosomal degradation 915:994 Wild-type and N-glycosylation-deficient TRPP2 is degraded in lysosomes, as shown by increased TRPP2 protein levels upon chemical inhibition of lysosomal degradation. 24719335 8 56 theme dominant 1242:1249 arg1 ADPLD 1277:1281 ADPLD 1277:1281 ADPLD 1277:1281 The non-catalytic β subunit of glucosidase II (GIIβ) is encoded by PRKCSH, one of the genes causing autosomal dominant polycystic liver disease (ADPLD). 24719335 8 56 theme dominant 1242:1249 arg1 disease 1268:1274 autosomal dominant polycystic liver disease 1232:1274 autosomal dominant polycystic liver disease (ADPLD) 1232:1282 The non-catalytic β subunit of glucosidase II (GIIβ) is encoded by PRKCSH, one of the genes causing autosomal dominant polycystic liver disease (ADPLD). 24719335 4 57 from asparagines 604:614 arg1 loop 643:646 the first extracellular loop 619:646 the first extracellular loop 619:646 Here we show, using a combination of mass spectrometry and biochemical approaches, that native TRPP2 is glycosylated at five asparagines in the first extracellular loop. 24719335 8 58 theme liver 1262:1266 arg1 ADPLD 1277:1281 ADPLD 1277:1281 ADPLD 1277:1281 The non-catalytic β subunit of glucosidase II (GIIβ) is encoded by PRKCSH, one of the genes causing autosomal dominant polycystic liver disease (ADPLD). 24719335 8 58 theme liver 1262:1266 arg1 disease 1268:1274 autosomal dominant polycystic liver disease 1232:1274 autosomal dominant polycystic liver disease (ADPLD) 1232:1282 The non-catalytic β subunit of glucosidase II (GIIβ) is encoded by PRKCSH, one of the genes causing autosomal dominant polycystic liver disease (ADPLD). 24719335 7 59 theme glycan 1106:1111 arg1 trimming 1113:1120 glycan trimming 1106:1120 glycan trimming of TRPP2 1106:1129 In addition, using pharmacological and genetic approaches, we demonstrate that glucosidase II (GII) mediates glycan trimming of TRPP2. 24719335 4 60 theme extracellular 629:641 arg1 loop 643:646 the first extracellular loop 619:646 the first extracellular loop 619:646 Here we show, using a combination of mass spectrometry and biochemical approaches, that native TRPP2 is glycosylated at five asparagines in the first extracellular loop. 24719335 5 61 theme efficient 683:691 arg1 biogenesis 693:702 the efficient biogenesis 679:702 the efficient biogenesis of TRPP2 679:711 Glycosylation is required for the efficient biogenesis of TRPP2 because mutations of the glycosylated asparagines result in strongly decreased protein expression of the ion channel. 24719335 2 62 theme nonselective 229:240 arg1 channel 249:255 a nonselective cation channel 227:255 a nonselective cation channel that is mutated in autosomal dominant polycystic kidney disease 227:319 Transient receptor potential channel TRPP2 is a nonselective cation channel that is mutated in autosomal dominant polycystic kidney disease. 24719335 2 62 theme nonselective 229:240 arg1 TRPP2 218:222 Transient receptor potential channel TRPP2 181:222 Transient receptor potential channel TRPP2 181:222 Transient receptor potential channel TRPP2 is a nonselective cation channel that is mutated in autosomal dominant polycystic kidney disease. 24719335 6 63 theme lysosomal 974:982 arg1 degradation 984:994 lysosomal degradation 974:994 lysosomal degradation 974:994 Wild-type and N-glycosylation-deficient TRPP2 is degraded in lysosomes, as shown by increased TRPP2 protein levels upon chemical inhibition of lysosomal degradation. 24719335 0 64 theme channel 77:83 arg1 TRPP2 85:89 the transient receptor potential channel TRPP2 44:89 the transient receptor potential channel TRPP2 44:89 N-glycosylation determines the abundance of the transient receptor potential channel TRPP2. 24719335 5 65 theme protein 792:798 arg1 expression 800:809 strongly decreased protein expression 773:809 strongly decreased protein expression of the ion channel 773:828 Glycosylation is required for the efficient biogenesis of TRPP2 because mutations of the glycosylated asparagines result in strongly decreased protein expression of the ion channel. 24719335 9 66 theme impaired 1289:1296 arg1 trimming 1321:1328 The impaired GIIβ-dependent glucose trimming 1285:1328 The impaired GIIβ-dependent glucose trimming of TRPP2 glycosylation in ADPLD 1285:1360 The impaired GIIβ-dependent glucose trimming of TRPP2 glycosylation in ADPLD may explain the decreased TRPP2 protein expression in Prkcsh(-/-) mice and the genetic interaction observed between TRPP2 and PRKCSH in ADPLD. 24719335 4 67 theme mass 516:519 arg1 spectrometry 521:532 mass spectrometry 516:532 mass spectrometry 516:532 Here we show, using a combination of mass spectrometry and biochemical approaches, that native TRPP2 is glycosylated at five asparagines in the first extracellular loop. 24719335 5 68 theme glycosylated 738:749 arg1 asparagines 751:761 the glycosylated asparagines 734:761 the glycosylated asparagines 734:761 Glycosylation is required for the efficient biogenesis of TRPP2 because mutations of the glycosylated asparagines result in strongly decreased protein expression of the ion channel. 24719335 9 69 theme glucose 1313:1319 arg1 trimming 1321:1328 The impaired GIIβ-dependent glucose trimming 1285:1328 The impaired GIIβ-dependent glucose trimming of TRPP2 glycosylation in ADPLD 1285:1360 The impaired GIIβ-dependent glucose trimming of TRPP2 glycosylation in ADPLD may explain the decreased TRPP2 protein expression in Prkcsh(-/-) mice and the genetic interaction observed between TRPP2 and PRKCSH in ADPLD. 24719335 1 70 dep biogenesis 135:144 arg1 the 131:133 the 131:133 the 131:133 Glycosylation plays a critical role in the biogenesis and function of membrane proteins. 24719335 9 71 theme glycosylation 1339:1351 arg1 trimming 1321:1328 The impaired GIIβ-dependent glucose trimming 1285:1328 The impaired GIIβ-dependent glucose trimming of TRPP2 glycosylation in ADPLD 1285:1360 The impaired GIIβ-dependent glucose trimming of TRPP2 glycosylation in ADPLD may explain the decreased TRPP2 protein expression in Prkcsh(-/-) mice and the genetic interaction observed between TRPP2 and PRKCSH in ADPLD. 24719335 3 72 gly glycosylation 381:393 arg1 glycosylation 437:449 N-linked glycosylation 428:449 N-linked glycosylation 428:449 TRPP2 has been shown to be heavily N-glycosylated, but the glycosylation sites and the biological role of N-linked glycosylation have not been investigated. 24719335 3 72 gly glycosylation 381:393 arg2 glycosylation 437:449 N-linked glycosylation 428:449 N-linked glycosylation 428:449 TRPP2 has been shown to be heavily N-glycosylated, but the glycosylation sites and the biological role of N-linked glycosylation have not been investigated. 24719335 3 72 gly glycosylation 381:393 arg2 sites 395:399 the glycosylation sites 377:399 the glycosylation sites 377:399 TRPP2 has been shown to be heavily N-glycosylated, but the glycosylation sites and the biological role of N-linked glycosylation have not been investigated. 24719335 4 73 gly glycosylated 583:594 arg2 asparagines 604:614 five asparagines 599:614 five asparagines in the first extracellular loop 599:646 Here we show, using a combination of mass spectrometry and biochemical approaches, that native TRPP2 is glycosylated at five asparagines in the first extracellular loop. 24719335 4 73 gly glycosylated 583:594 arg1 TRPP2 574:578 native TRPP2 567:578 native TRPP2 567:578 Here we show, using a combination of mass spectrometry and biochemical approaches, that native TRPP2 is glycosylated at five asparagines in the first extracellular loop. 24719335 5 74 gly glycosylated 738:749 arg1 asparagines 751:761 the glycosylated asparagines 734:761 the glycosylated asparagines 734:761 Glycosylation is required for the efficient biogenesis of TRPP2 because mutations of the glycosylated asparagines result in strongly decreased protein expression of the ion channel. 24719335 3 75 theme glycosylation 437:449 arg1 sites 395:399 the glycosylation sites 377:399 the glycosylation sites 377:399 TRPP2 has been shown to be heavily N-glycosylated, but the glycosylation sites and the biological role of N-linked glycosylation have not been investigated. 24719335 3 75 theme glycosylation 437:449 arg1 role 420:423 the biological role 405:423 the biological role of N-linked glycosylation 405:449 TRPP2 has been shown to be heavily N-glycosylated, but the glycosylation sites and the biological role of N-linked glycosylation have not been investigated. 24719335 3 75 theme glycosylation 437:449 arg1 glycosylation 437:449 N-linked glycosylation 428:449 N-linked glycosylation 428:449 TRPP2 has been shown to be heavily N-glycosylated, but the glycosylation sites and the biological role of N-linked glycosylation have not been investigated. 24719335 3 76 theme glycosylation 381:393 arg1 sites 395:399 the glycosylation sites 377:399 the glycosylation sites 377:399 TRPP2 has been shown to be heavily N-glycosylated, but the glycosylation sites and the biological role of N-linked glycosylation have not been investigated. 24719335 3 76 theme glycosylation 381:393 arg1 glycosylation 437:449 N-linked glycosylation 428:449 N-linked glycosylation 428:449 TRPP2 has been shown to be heavily N-glycosylated, but the glycosylation sites and the biological role of N-linked glycosylation have not been investigated. 24719335 2 77 theme receptor 191:198 arg1 channel 249:255 a nonselective cation channel 227:255 a nonselective cation channel that is mutated in autosomal dominant polycystic kidney disease 227:319 Transient receptor potential channel TRPP2 is a nonselective cation channel that is mutated in autosomal dominant polycystic kidney disease. 24719335 2 77 theme receptor 191:198 arg1 TRPP2 218:222 Transient receptor potential channel TRPP2 181:222 Transient receptor potential channel TRPP2 181:222 Transient receptor potential channel TRPP2 is a nonselective cation channel that is mutated in autosomal dominant polycystic kidney disease. 24719335 3 78 gly N-glycosylated 357:370 arg1 TRPP2 322:326 TRPP2 322:326 TRPP2 322:326 TRPP2 has been shown to be heavily N-glycosylated, but the glycosylation sites and the biological role of N-linked glycosylation have not been investigated. 24719335 10 79 from importance 1544:1553 arg1 control 1621:1627 the control 1617:1627 the control of biogenesis and stability of TRPP2 1617:1664 These results highlight the biological importance of N-linked glycosylation and GII-mediated glycan trimming in the control of biogenesis and stability of TRPP2. 24719335 5 80 theme ion 818:820 arg1 channel 822:828 the ion channel 814:828 the ion channel 814:828 Glycosylation is required for the efficient biogenesis of TRPP2 because mutations of the glycosylated asparagines result in strongly decreased protein expression of the ion channel. 24719335 9 81 theme decreased 1378:1386 arg1 expression 1402:1411 the decreased TRPP2 protein expression 1374:1411 the decreased TRPP2 protein expression in Prkcsh(-/-) mice 1374:1431 The impaired GIIβ-dependent glucose trimming of TRPP2 glycosylation in ADPLD may explain the decreased TRPP2 protein expression in Prkcsh(-/-) mice and the genetic interaction observed between TRPP2 and PRKCSH in ADPLD. 24719335 8 82 theme β 1150:1150 arg1 GIIβ 1179:1182 GIIβ 1179:1182 GIIβ 1179:1182 The non-catalytic β subunit of glucosidase II (GIIβ) is encoded by PRKCSH, one of the genes causing autosomal dominant polycystic liver disease (ADPLD). 24719335 8 82 theme β 1150:1150 arg1 subunit 1152:1158 The non-catalytic β subunit 1132:1158 The non-catalytic β subunit of glucosidase II (GIIβ) 1132:1183 The non-catalytic β subunit of glucosidase II (GIIβ) is encoded by PRKCSH, one of the genes causing autosomal dominant polycystic liver disease (ADPLD). 24719335 9 83 from PRKCSH 1488:1493 arg1 ADPLD 1498:1502 ADPLD 1498:1502 ADPLD 1498:1502 The impaired GIIβ-dependent glucose trimming of TRPP2 glycosylation in ADPLD may explain the decreased TRPP2 protein expression in Prkcsh(-/-) mice and the genetic interaction observed between TRPP2 and PRKCSH in ADPLD. 24719335 3 84 theme biological 409:418 arg1 role 420:423 the biological role 405:423 the biological role of N-linked glycosylation 405:449 TRPP2 has been shown to be heavily N-glycosylated, but the glycosylation sites and the biological role of N-linked glycosylation have not been investigated. 24719335 4 85 theme approaches 550:559 arg1 combination 501:511 a combination 499:511 a combination of mass spectrometry and biochemical approaches 499:559 Here we show, using a combination of mass spectrometry and biochemical approaches, that native TRPP2 is glycosylated at five asparagines in the first extracellular loop. 24719335 9 86 theme protein 1394:1400 arg1 expression 1402:1411 the decreased TRPP2 protein expression 1374:1411 the decreased TRPP2 protein expression in Prkcsh(-/-) mice 1374:1431 The impaired GIIβ-dependent glucose trimming of TRPP2 glycosylation in ADPLD may explain the decreased TRPP2 protein expression in Prkcsh(-/-) mice and the genetic interaction observed between TRPP2 and PRKCSH in ADPLD. 24719335 9 87 from expression 1402:1411 arg1 mice 1428:1431 Prkcsh(-/-) mice 1416:1431 Prkcsh(-/-) mice 1416:1431 The impaired GIIβ-dependent glucose trimming of TRPP2 glycosylation in ADPLD may explain the decreased TRPP2 protein expression in Prkcsh(-/-) mice and the genetic interaction observed between TRPP2 and PRKCSH in ADPLD. 24719335 9 88 from TRPP2 1478:1482 arg1 ADPLD 1498:1502 ADPLD 1498:1502 ADPLD 1498:1502 The impaired GIIβ-dependent glucose trimming of TRPP2 glycosylation in ADPLD may explain the decreased TRPP2 protein expression in Prkcsh(-/-) mice and the genetic interaction observed between TRPP2 and PRKCSH in ADPLD. 24719335 2 89 theme channel 210:216 arg1 channel 249:255 a nonselective cation channel 227:255 a nonselective cation channel that is mutated in autosomal dominant polycystic kidney disease 227:319 Transient receptor potential channel TRPP2 is a nonselective cation channel that is mutated in autosomal dominant polycystic kidney disease. 24719335 2 89 theme channel 210:216 arg1 TRPP2 218:222 Transient receptor potential channel TRPP2 181:222 Transient receptor potential channel TRPP2 181:222 Transient receptor potential channel TRPP2 is a nonselective cation channel that is mutated in autosomal dominant polycystic kidney disease. 24719335 4 90 theme first 623:627 arg1 loop 643:646 the first extracellular loop 619:646 the first extracellular loop 619:646 Here we show, using a combination of mass spectrometry and biochemical approaches, that native TRPP2 is glycosylated at five asparagines in the first extracellular loop. 24719335 10 91 theme N-linked 1558:1565 arg1 glycosylation 1567:1579 N-linked glycosylation 1558:1579 N-linked glycosylation 1558:1579 These results highlight the biological importance of N-linked glycosylation and GII-mediated glycan trimming in the control of biogenesis and stability of TRPP2. 26367528 5 0 theme neuroserpin 1161:1171 arg1 mutant 1151:1156 the G392E mutant 1141:1156 the G392E mutant of neuroserpin that causes severe, early-onset dementia 1141:1212 Asparagine residue 401 is not glycosylated in wild type neuroserpin and in several polymerogenic variants that cause FENIB, but partial glycosylation was observed in the G392E mutant of neuroserpin that causes severe, early-onset dementia. 26367528 7 1 theme proteasomal 1517:1527 arg1 impairment 1529:1538 proteasomal impairment 1517:1538 proteasomal impairment 1517:1538 This C-terminal lability is not required for neuroserpin polymerisation in the endoplasmic reticulum, but the additional glycan facilitates degradation of the mutant protein during proteasomal impairment. 26367528 2 2 theme glycosylation 405:417 arg1 sites 419:423 predicted glycosylation sites 395:423 predicted glycosylation sites at asparagines 157, 321 and 401 395:455 Neuroserpin is a glycoprotein with predicted glycosylation sites at asparagines 157, 321 and 401. 26367528 0 3 theme endoplasmic 89:99 arg1 reticulum 101:109 the endoplasmic reticulum 85:109 the endoplasmic reticulum 85:109 Interactions between N-linked glycosylation and polymerisation of neuroserpin within the endoplasmic reticulum. 26367528 4 4 from effects 895:901 arg1 dynamics 927:934 local conformational dynamics 906:934 local conformational dynamics that can contribute to polymerisation 906:972 Our data show that glycosylation at N157 and N321 plays an important role in maintaining the monomeric state of neuroserpin, and we propose this is the result of steric hindrance or effects on local conformational dynamics that can contribute to polymerisation. 26367528 1 5 theme point 189:193 arg1 mutations 195:203 point mutations 189:203 point mutations that alter its conformational stability 189:243 The neuronal serpin neuroserpin undergoes polymerisation as a consequence of point mutations that alter its conformational stability, leading to a neurodegenerative dementia called familial encephalopathy with neuroserpin inclusion bodies (FENIB). 26367528 1 6 theme familial 293:300 arg1 encephalopathy 302:315 familial encephalopathy 293:315 familial encephalopathy with neuroserpin inclusion bodies (FENIB) 293:357 The neuronal serpin neuroserpin undergoes polymerisation as a consequence of point mutations that alter its conformational stability, leading to a neurodegenerative dementia called familial encephalopathy with neuroserpin inclusion bodies (FENIB). 26367528 7 7 theme endoplasmic 1415:1425 arg1 reticulum 1427:1435 the endoplasmic reticulum 1411:1435 the endoplasmic reticulum 1411:1435 This C-terminal lability is not required for neuroserpin polymerisation in the endoplasmic reticulum, but the additional glycan facilitates degradation of the mutant protein during proteasomal impairment. 26367528 2 8 theme predicted 395:403 arg1 sites 419:423 predicted glycosylation sites 395:423 predicted glycosylation sites at asparagines 157, 321 and 401 395:455 Neuroserpin is a glycoprotein with predicted glycosylation sites at asparagines 157, 321 and 401. 26367528 0 9 link N-linked 21:28 arg1 glycosylation 30:42 N-linked glycosylation 21:42 N-linked glycosylation 21:42 Interactions between N-linked glycosylation and polymerisation of neuroserpin within the endoplasmic reticulum. 26367528 4 10 theme monomeric 806:814 arg1 state 816:820 the monomeric state 802:820 the monomeric state of neuroserpin 802:835 Our data show that glycosylation at N157 and N321 plays an important role in maintaining the monomeric state of neuroserpin, and we propose this is the result of steric hindrance or effects on local conformational dynamics that can contribute to polymerisation. 26367528 8 11 theme variant-specific 1589:1604 arg1 events 1629:1634 normal and variant-specific N-linked glycosylation events 1578:1634 normal and variant-specific N-linked glycosylation events 1578:1634 In summary, our results indicate how normal and variant-specific N-linked glycosylation events relate to intracellular folding, misfolding, degradation and polymerisation of neuroserpin. 26367528 7 12 theme protein 1502:1508 arg1 degradation 1476:1486 degradation 1476:1486 degradation of the mutant protein 1476:1508 This C-terminal lability is not required for neuroserpin polymerisation in the endoplasmic reticulum, but the additional glycan facilitates degradation of the mutant protein during proteasomal impairment. 26367528 3 13 used used 461:464 arg2 We 458:459 We 458:459 We 458:459 We used site-directed mutagenesis, transient transfection, western blot, metabolic labelling and ELISA to probe the relationship between glycosylation, folding, polymerisation and degradation of neuroserpin in validated cell models of health and disease. 26367528 7 14 from polymerisation 1393:1406 arg1 reticulum 1427:1435 the endoplasmic reticulum 1411:1435 the endoplasmic reticulum 1411:1435 This C-terminal lability is not required for neuroserpin polymerisation in the endoplasmic reticulum, but the additional glycan facilitates degradation of the mutant protein during proteasomal impairment. 26367528 6 15 theme end 1296:1298 arg1 lability 1269:1276 lability 1269:1276 lability of the C-terminal end of neuroserpin in its native state 1269:1333 Our findings indicate that N401 glycosylation reports lability of the C-terminal end of neuroserpin in its native state. 26367528 1 16 theme mutations 195:203 arg1 polymerisation 154:167 polymerisation 154:167 polymerisation 154:167 The neuronal serpin neuroserpin undergoes polymerisation as a consequence of point mutations that alter its conformational stability, leading to a neurodegenerative dementia called familial encephalopathy with neuroserpin inclusion bodies (FENIB). 26367528 1 16 theme mutations 195:203 arg1 consequence 174:184 a consequence 172:184 a consequence of point mutations that alter its conformational stability 172:243 The neuronal serpin neuroserpin undergoes polymerisation as a consequence of point mutations that alter its conformational stability, leading to a neurodegenerative dementia called familial encephalopathy with neuroserpin inclusion bodies (FENIB). 26367528 5 17 theme G392E 1145:1149 arg1 mutant 1151:1156 the G392E mutant 1141:1156 the G392E mutant of neuroserpin that causes severe, early-onset dementia 1141:1212 Asparagine residue 401 is not glycosylated in wild type neuroserpin and in several polymerogenic variants that cause FENIB, but partial glycosylation was observed in the G392E mutant of neuroserpin that causes severe, early-onset dementia. 26367528 6 18 theme neuroserpin 1303:1313 arg1 end 1296:1298 the C-terminal end 1281:1298 the C-terminal end of neuroserpin 1281:1313 Our findings indicate that N401 glycosylation reports lability of the C-terminal end of neuroserpin in its native state. 26367528 5 19 theme wild 1021:1024 arg1 neuroserpin 1031:1041 wild type neuroserpin 1021:1041 wild type neuroserpin 1021:1041 Asparagine residue 401 is not glycosylated in wild type neuroserpin and in several polymerogenic variants that cause FENIB, but partial glycosylation was observed in the G392E mutant of neuroserpin that causes severe, early-onset dementia. 26367528 7 20 theme neuroserpin 1381:1391 arg1 polymerisation 1393:1406 neuroserpin polymerisation 1381:1406 neuroserpin polymerisation in the endoplasmic reticulum 1381:1435 This C-terminal lability is not required for neuroserpin polymerisation in the endoplasmic reticulum, but the additional glycan facilitates degradation of the mutant protein during proteasomal impairment. 26367528 4 21 from result 865:870 arg1 dynamics 927:934 local conformational dynamics 906:934 local conformational dynamics that can contribute to polymerisation 906:972 Our data show that glycosylation at N157 and N321 plays an important role in maintaining the monomeric state of neuroserpin, and we propose this is the result of steric hindrance or effects on local conformational dynamics that can contribute to polymerisation. 26367528 4 22 theme hindrance 882:890 arg1 effects 895:901 effects 895:901 effects on local conformational dynamics that can contribute to polymerisation 895:972 Our data show that glycosylation at N157 and N321 plays an important role in maintaining the monomeric state of neuroserpin, and we propose this is the result of steric hindrance or effects on local conformational dynamics that can contribute to polymerisation. 26367528 4 22 theme hindrance 882:890 arg1 result 865:870 the result 861:870 the result of steric hindrance 861:890 Our data show that glycosylation at N157 and N321 plays an important role in maintaining the monomeric state of neuroserpin, and we propose this is the result of steric hindrance or effects on local conformational dynamics that can contribute to polymerisation. 26367528 4 22 theme hindrance 882:890 arg1 this 853:856 this 853:856 this 853:856 Our data show that glycosylation at N157 and N321 plays an important role in maintaining the monomeric state of neuroserpin, and we propose this is the result of steric hindrance or effects on local conformational dynamics that can contribute to polymerisation. 26367528 5 23 theme Asparagine 975:984 arg1 residue 986:992 Asparagine residue 401 975:996 Asparagine residue 401 975:996 Asparagine residue 401 is not glycosylated in wild type neuroserpin and in several polymerogenic variants that cause FENIB, but partial glycosylation was observed in the G392E mutant of neuroserpin that causes severe, early-onset dementia. 26367528 4 24 theme conformational 912:925 arg1 dynamics 927:934 local conformational dynamics 906:934 local conformational dynamics that can contribute to polymerisation 906:972 Our data show that glycosylation at N157 and N321 plays an important role in maintaining the monomeric state of neuroserpin, and we propose this is the result of steric hindrance or effects on local conformational dynamics that can contribute to polymerisation. 26367528 5 25 located observed 1129:1136 arg2 glycosylation 1111:1123 partial glycosylation 1103:1123 partial glycosylation 1103:1123 Asparagine residue 401 is not glycosylated in wild type neuroserpin and in several polymerogenic variants that cause FENIB, but partial glycosylation was observed in the G392E mutant of neuroserpin that causes severe, early-onset dementia. 26367528 5 25 located observed 1129:1136 arg1 mutant 1151:1156 the G392E mutant 1141:1156 the G392E mutant of neuroserpin that causes severe, early-onset dementia 1141:1212 Asparagine residue 401 is not glycosylated in wild type neuroserpin and in several polymerogenic variants that cause FENIB, but partial glycosylation was observed in the G392E mutant of neuroserpin that causes severe, early-onset dementia. 26367528 8 26 theme normal 1578:1583 arg1 events 1629:1634 normal and variant-specific N-linked glycosylation events 1578:1634 normal and variant-specific N-linked glycosylation events 1578:1634 In summary, our results indicate how normal and variant-specific N-linked glycosylation events relate to intracellular folding, misfolding, degradation and polymerisation of neuroserpin. 26367528 1 27 theme neuroserpin 322:332 arg1 bodies 344:349 neuroserpin inclusion bodies 322:349 neuroserpin inclusion bodies (FENIB) 322:357 The neuronal serpin neuroserpin undergoes polymerisation as a consequence of point mutations that alter its conformational stability, leading to a neurodegenerative dementia called familial encephalopathy with neuroserpin inclusion bodies (FENIB). 26367528 1 27 theme neuroserpin 322:332 arg1 FENIB 352:356 FENIB 352:356 FENIB 352:356 The neuronal serpin neuroserpin undergoes polymerisation as a consequence of point mutations that alter its conformational stability, leading to a neurodegenerative dementia called familial encephalopathy with neuroserpin inclusion bodies (FENIB). 26367528 4 28 theme steric 875:880 arg1 hindrance 882:890 steric hindrance 875:890 steric hindrance 875:890 Our data show that glycosylation at N157 and N321 plays an important role in maintaining the monomeric state of neuroserpin, and we propose this is the result of steric hindrance or effects on local conformational dynamics that can contribute to polymerisation. 26367528 4 29 theme important 772:780 arg1 role 782:785 an important role 769:785 an important role 769:785 Our data show that glycosylation at N157 and N321 plays an important role in maintaining the monomeric state of neuroserpin, and we propose this is the result of steric hindrance or effects on local conformational dynamics that can contribute to polymerisation. 26367528 3 30 theme site-directed 466:478 arg1 mutagenesis 480:490 site-directed mutagenesis 466:490 site-directed mutagenesis 466:490 We used site-directed mutagenesis, transient transfection, western blot, metabolic labelling and ELISA to probe the relationship between glycosylation, folding, polymerisation and degradation of neuroserpin in validated cell models of health and disease. 26367528 7 31 theme additional 1446:1455 arg1 glycan 1457:1462 the additional glycan 1442:1462 the additional glycan 1442:1462 This C-terminal lability is not required for neuroserpin polymerisation in the endoplasmic reticulum, but the additional glycan facilitates degradation of the mutant protein during proteasomal impairment. 26367528 1 32 theme inclusion 334:342 arg1 bodies 344:349 neuroserpin inclusion bodies 322:349 neuroserpin inclusion bodies (FENIB) 322:357 The neuronal serpin neuroserpin undergoes polymerisation as a consequence of point mutations that alter its conformational stability, leading to a neurodegenerative dementia called familial encephalopathy with neuroserpin inclusion bodies (FENIB). 26367528 1 32 theme inclusion 334:342 arg1 FENIB 352:356 FENIB 352:356 FENIB 352:356 The neuronal serpin neuroserpin undergoes polymerisation as a consequence of point mutations that alter its conformational stability, leading to a neurodegenerative dementia called familial encephalopathy with neuroserpin inclusion bodies (FENIB). 26367528 1 33 theme neuronal 116:123 arg1 neuroserpin 132:142 The neuronal serpin neuroserpin 112:142 The neuronal serpin neuroserpin 112:142 The neuronal serpin neuroserpin undergoes polymerisation as a consequence of point mutations that alter its conformational stability, leading to a neurodegenerative dementia called familial encephalopathy with neuroserpin inclusion bodies (FENIB). 26367528 6 34 theme C-terminal 1285:1294 arg1 end 1296:1298 the C-terminal end 1281:1298 the C-terminal end of neuroserpin 1281:1313 Our findings indicate that N401 glycosylation reports lability of the C-terminal end of neuroserpin in its native state. 26367528 1 35 theme conformational 220:233 arg1 stability 235:243 its conformational stability 216:243 its conformational stability 216:243 The neuronal serpin neuroserpin undergoes polymerisation as a consequence of point mutations that alter its conformational stability, leading to a neurodegenerative dementia called familial encephalopathy with neuroserpin inclusion bodies (FENIB). 26367528 0 36 theme N-linked 21:28 arg1 glycosylation 30:42 N-linked glycosylation 21:42 N-linked glycosylation 21:42 Interactions between N-linked glycosylation and polymerisation of neuroserpin within the endoplasmic reticulum. 26367528 8 37 theme intracellular 1646:1658 arg1 folding 1660:1666 intracellular folding 1646:1666 intracellular folding 1646:1666 In summary, our results indicate how normal and variant-specific N-linked glycosylation events relate to intracellular folding, misfolding, degradation and polymerisation of neuroserpin. 26367528 5 38 theme partial 1103:1109 arg1 glycosylation 1111:1123 partial glycosylation 1103:1123 partial glycosylation 1103:1123 Asparagine residue 401 is not glycosylated in wild type neuroserpin and in several polymerogenic variants that cause FENIB, but partial glycosylation was observed in the G392E mutant of neuroserpin that causes severe, early-onset dementia. 26367528 1 39 theme serpin 125:130 arg1 neuroserpin 132:142 The neuronal serpin neuroserpin 112:142 The neuronal serpin neuroserpin 112:142 The neuronal serpin neuroserpin undergoes polymerisation as a consequence of point mutations that alter its conformational stability, leading to a neurodegenerative dementia called familial encephalopathy with neuroserpin inclusion bodies (FENIB). 26367528 8 40 theme glycosylation 1615:1627 arg1 events 1629:1634 normal and variant-specific N-linked glycosylation events 1578:1634 normal and variant-specific N-linked glycosylation events 1578:1634 In summary, our results indicate how normal and variant-specific N-linked glycosylation events relate to intracellular folding, misfolding, degradation and polymerisation of neuroserpin. 26367528 3 41 theme western 517:523 arg1 blot 525:528 western blot 517:528 western blot 517:528 We used site-directed mutagenesis, transient transfection, western blot, metabolic labelling and ELISA to probe the relationship between glycosylation, folding, polymerisation and degradation of neuroserpin in validated cell models of health and disease. 26367528 3 42 theme disease 704:710 arg1 models 683:688 validated cell models 668:688 validated cell models of health and disease 668:710 We used site-directed mutagenesis, transient transfection, western blot, metabolic labelling and ELISA to probe the relationship between glycosylation, folding, polymerisation and degradation of neuroserpin in validated cell models of health and disease. 26367528 5 43 theme several 1050:1056 arg1 variants 1072:1079 several polymerogenic variants 1050:1079 several polymerogenic variants that cause FENIB 1050:1096 Asparagine residue 401 is not glycosylated in wild type neuroserpin and in several polymerogenic variants that cause FENIB, but partial glycosylation was observed in the G392E mutant of neuroserpin that causes severe, early-onset dementia. 26367528 6 44 theme native 1322:1327 arg1 state 1329:1333 its native state 1318:1333 its native state 1318:1333 Our findings indicate that N401 glycosylation reports lability of the C-terminal end of neuroserpin in its native state. 26367528 3 45 theme transient 493:501 arg1 transfection 503:514 transient transfection 493:514 transient transfection 493:514 We used site-directed mutagenesis, transient transfection, western blot, metabolic labelling and ELISA to probe the relationship between glycosylation, folding, polymerisation and degradation of neuroserpin in validated cell models of health and disease. 26367528 2 46 gly glycosylation 405:417 arg2 asparagines 428:438 asparagines 157, 321 and 401 428:455 asparagines 157, 321 and 401 428:455 Neuroserpin is a glycoprotein with predicted glycosylation sites at asparagines 157, 321 and 401. 26367528 2 46 gly glycosylation 405:417 arg2 sites 419:423 predicted glycosylation sites 395:423 predicted glycosylation sites at asparagines 157, 321 and 401 395:455 Neuroserpin is a glycoprotein with predicted glycosylation sites at asparagines 157, 321 and 401. 26367528 3 47 theme neuroserpin 653:663 arg1 folding 610:616 folding 610:616 folding 610:616 We used site-directed mutagenesis, transient transfection, western blot, metabolic labelling and ELISA to probe the relationship between glycosylation, folding, polymerisation and degradation of neuroserpin in validated cell models of health and disease. 26367528 3 47 theme neuroserpin 653:663 arg1 glycosylation 595:607 glycosylation 595:607 glycosylation 595:607 We used site-directed mutagenesis, transient transfection, western blot, metabolic labelling and ELISA to probe the relationship between glycosylation, folding, polymerisation and degradation of neuroserpin in validated cell models of health and disease. 26367528 3 47 theme neuroserpin 653:663 arg1 degradation 638:648 degradation 638:648 degradation 638:648 We used site-directed mutagenesis, transient transfection, western blot, metabolic labelling and ELISA to probe the relationship between glycosylation, folding, polymerisation and degradation of neuroserpin in validated cell models of health and disease. 26367528 3 47 theme neuroserpin 653:663 arg1 polymerisation 619:632 polymerisation 619:632 polymerisation 619:632 We used site-directed mutagenesis, transient transfection, western blot, metabolic labelling and ELISA to probe the relationship between glycosylation, folding, polymerisation and degradation of neuroserpin in validated cell models of health and disease. 26367528 1 48 with encephalopathy 302:315 arg1 bodies 344:349 neuroserpin inclusion bodies 322:349 neuroserpin inclusion bodies (FENIB) 322:357 The neuronal serpin neuroserpin undergoes polymerisation as a consequence of point mutations that alter its conformational stability, leading to a neurodegenerative dementia called familial encephalopathy with neuroserpin inclusion bodies (FENIB). 26367528 1 48 with encephalopathy 302:315 arg1 FENIB 352:356 FENIB 352:356 FENIB 352:356 The neuronal serpin neuroserpin undergoes polymerisation as a consequence of point mutations that alter its conformational stability, leading to a neurodegenerative dementia called familial encephalopathy with neuroserpin inclusion bodies (FENIB). 26367528 7 49 theme C-terminal 1341:1350 arg1 lability 1352:1359 This C-terminal lability 1336:1359 This C-terminal lability 1336:1359 This C-terminal lability is not required for neuroserpin polymerisation in the endoplasmic reticulum, but the additional glycan facilitates degradation of the mutant protein during proteasomal impairment. 26367528 2 50 gly glycoprotein 377:388 arg1 glycoprotein 377:388 a glycoprotein 375:388 a glycoprotein with predicted glycosylation sites at asparagines 157, 321 and 401 375:455 Neuroserpin is a glycoprotein with predicted glycosylation sites at asparagines 157, 321 and 401. 26367528 2 50 gly glycoprotein 377:388 arg1 Neuroserpin 360:370 Neuroserpin 360:370 Neuroserpin 360:370 Neuroserpin is a glycoprotein with predicted glycosylation sites at asparagines 157, 321 and 401. 26367528 2 51 with glycoprotein 377:388 arg1 sites 419:423 predicted glycosylation sites 395:423 predicted glycosylation sites at asparagines 157, 321 and 401 395:455 Neuroserpin is a glycoprotein with predicted glycosylation sites at asparagines 157, 321 and 401. 26367528 2 52 from asparagines 428:438 arg1 sites 419:423 predicted glycosylation sites 395:423 predicted glycosylation sites at asparagines 157, 321 and 401 395:455 Neuroserpin is a glycoprotein with predicted glycosylation sites at asparagines 157, 321 and 401. 26367528 3 53 theme metabolic 531:539 arg1 labelling 541:549 metabolic labelling 531:549 metabolic labelling 531:549 We used site-directed mutagenesis, transient transfection, western blot, metabolic labelling and ELISA to probe the relationship between glycosylation, folding, polymerisation and degradation of neuroserpin in validated cell models of health and disease. 26367528 5 54 dep severe 1185:1190 arg1 early-onset 1193:1203 early-onset 1193:1203 early-onset 1193:1203 Asparagine residue 401 is not glycosylated in wild type neuroserpin and in several polymerogenic variants that cause FENIB, but partial glycosylation was observed in the G392E mutant of neuroserpin that causes severe, early-onset dementia. 26367528 4 55 gly glycosylation 732:744 arg1 N321 758:761 N321 758:761 N321 758:761 Our data show that glycosylation at N157 and N321 plays an important role in maintaining the monomeric state of neuroserpin, and we propose this is the result of steric hindrance or effects on local conformational dynamics that can contribute to polymerisation. 26367528 4 55 gly glycosylation 732:744 arg2 N321 758:761 N321 758:761 N321 758:761 Our data show that glycosylation at N157 and N321 plays an important role in maintaining the monomeric state of neuroserpin, and we propose this is the result of steric hindrance or effects on local conformational dynamics that can contribute to polymerisation. 26367528 4 55 gly glycosylation 732:744 arg1 N157 749:752 N157 749:752 N157 749:752 Our data show that glycosylation at N157 and N321 plays an important role in maintaining the monomeric state of neuroserpin, and we propose this is the result of steric hindrance or effects on local conformational dynamics that can contribute to polymerisation. 26367528 4 55 gly glycosylation 732:744 arg2 N157 749:752 N157 749:752 N157 749:752 Our data show that glycosylation at N157 and N321 plays an important role in maintaining the monomeric state of neuroserpin, and we propose this is the result of steric hindrance or effects on local conformational dynamics that can contribute to polymerisation. 26367528 3 56 theme health 693:698 arg1 models 683:688 validated cell models 668:688 validated cell models of health and disease 668:710 We used site-directed mutagenesis, transient transfection, western blot, metabolic labelling and ELISA to probe the relationship between glycosylation, folding, polymerisation and degradation of neuroserpin in validated cell models of health and disease. 26367528 4 57 theme local 906:910 arg1 dynamics 927:934 local conformational dynamics 906:934 local conformational dynamics that can contribute to polymerisation 906:972 Our data show that glycosylation at N157 and N321 plays an important role in maintaining the monomeric state of neuroserpin, and we propose this is the result of steric hindrance or effects on local conformational dynamics that can contribute to polymerisation. 26367528 5 58 gly glycosylation 1111:1123 arg1 mutant 1151:1156 the G392E mutant 1141:1156 the G392E mutant of neuroserpin that causes severe, early-onset dementia 1141:1212 Asparagine residue 401 is not glycosylated in wild type neuroserpin and in several polymerogenic variants that cause FENIB, but partial glycosylation was observed in the G392E mutant of neuroserpin that causes severe, early-onset dementia. 26367528 7 59 theme mutant 1495:1500 arg1 protein 1502:1508 the mutant protein 1491:1508 the mutant protein 1491:1508 This C-terminal lability is not required for neuroserpin polymerisation in the endoplasmic reticulum, but the additional glycan facilitates degradation of the mutant protein during proteasomal impairment. 26367528 8 60 theme neuroserpin 1715:1725 arg1 polymerisation 1697:1710 polymerisation 1697:1710 polymerisation 1697:1710 In summary, our results indicate how normal and variant-specific N-linked glycosylation events relate to intracellular folding, misfolding, degradation and polymerisation of neuroserpin. 26367528 8 60 theme neuroserpin 1715:1725 arg1 degradation 1681:1691 degradation 1681:1691 degradation 1681:1691 In summary, our results indicate how normal and variant-specific N-linked glycosylation events relate to intracellular folding, misfolding, degradation and polymerisation of neuroserpin. 26367528 8 60 theme neuroserpin 1715:1725 arg1 misfolding 1669:1678 misfolding 1669:1678 misfolding 1669:1678 In summary, our results indicate how normal and variant-specific N-linked glycosylation events relate to intracellular folding, misfolding, degradation and polymerisation of neuroserpin. 26367528 8 60 theme neuroserpin 1715:1725 arg1 folding 1660:1666 intracellular folding 1646:1666 intracellular folding 1646:1666 In summary, our results indicate how normal and variant-specific N-linked glycosylation events relate to intracellular folding, misfolding, degradation and polymerisation of neuroserpin. 26367528 5 61 theme type 1026:1029 arg1 neuroserpin 1031:1041 wild type neuroserpin 1021:1041 wild type neuroserpin 1021:1041 Asparagine residue 401 is not glycosylated in wild type neuroserpin and in several polymerogenic variants that cause FENIB, but partial glycosylation was observed in the G392E mutant of neuroserpin that causes severe, early-onset dementia. 26367528 3 62 theme cell 678:681 arg1 models 683:688 validated cell models 668:688 validated cell models of health and disease 668:710 We used site-directed mutagenesis, transient transfection, western blot, metabolic labelling and ELISA to probe the relationship between glycosylation, folding, polymerisation and degradation of neuroserpin in validated cell models of health and disease. 26367528 5 63 theme polymerogenic 1058:1070 arg1 variants 1072:1079 several polymerogenic variants 1050:1079 several polymerogenic variants that cause FENIB 1050:1096 Asparagine residue 401 is not glycosylated in wild type neuroserpin and in several polymerogenic variants that cause FENIB, but partial glycosylation was observed in the G392E mutant of neuroserpin that causes severe, early-onset dementia. 26367528 6 64 from lability 1269:1276 arg1 state 1329:1333 its native state 1318:1333 its native state 1318:1333 Our findings indicate that N401 glycosylation reports lability of the C-terminal end of neuroserpin in its native state. 26367528 4 65 theme neuroserpin 825:835 arg1 state 816:820 the monomeric state 802:820 the monomeric state of neuroserpin 802:835 Our data show that glycosylation at N157 and N321 plays an important role in maintaining the monomeric state of neuroserpin, and we propose this is the result of steric hindrance or effects on local conformational dynamics that can contribute to polymerisation. 26367528 4 66 from N321 758:761 arg1 glycosylation 732:744 glycosylation 732:744 glycosylation at N157 and N321 732:761 Our data show that glycosylation at N157 and N321 plays an important role in maintaining the monomeric state of neuroserpin, and we propose this is the result of steric hindrance or effects on local conformational dynamics that can contribute to polymerisation. 26367528 5 67 gly glycosylated 1005:1016 arg1 variants 1072:1079 several polymerogenic variants 1050:1079 several polymerogenic variants that cause FENIB 1050:1096 Asparagine residue 401 is not glycosylated in wild type neuroserpin and in several polymerogenic variants that cause FENIB, but partial glycosylation was observed in the G392E mutant of neuroserpin that causes severe, early-onset dementia. 26367528 5 67 gly glycosylated 1005:1016 arg1 residue 986:992 Asparagine residue 401 975:996 Asparagine residue 401 975:996 Asparagine residue 401 is not glycosylated in wild type neuroserpin and in several polymerogenic variants that cause FENIB, but partial glycosylation was observed in the G392E mutant of neuroserpin that causes severe, early-onset dementia. 26367528 5 67 gly glycosylated 1005:1016 arg2 residue 986:992 Asparagine residue 401 975:996 Asparagine residue 401 975:996 Asparagine residue 401 is not glycosylated in wild type neuroserpin and in several polymerogenic variants that cause FENIB, but partial glycosylation was observed in the G392E mutant of neuroserpin that causes severe, early-onset dementia. 26367528 5 67 gly glycosylated 1005:1016 arg1 neuroserpin 1031:1041 wild type neuroserpin 1021:1041 wild type neuroserpin 1021:1041 Asparagine residue 401 is not glycosylated in wild type neuroserpin and in several polymerogenic variants that cause FENIB, but partial glycosylation was observed in the G392E mutant of neuroserpin that causes severe, early-onset dementia. 26367528 6 68 theme N401 1242:1245 arg1 glycosylation 1247:1259 N401 glycosylation 1242:1259 N401 glycosylation 1242:1259 Our findings indicate that N401 glycosylation reports lability of the C-terminal end of neuroserpin in its native state. 26367528 8 69 theme N-linked 1606:1613 arg1 events 1629:1634 normal and variant-specific N-linked glycosylation events 1578:1634 normal and variant-specific N-linked glycosylation events 1578:1634 In summary, our results indicate how normal and variant-specific N-linked glycosylation events relate to intracellular folding, misfolding, degradation and polymerisation of neuroserpin. 26367528 3 70 gly glycosylation 595:607 arg1 neuroserpin 653:663 neuroserpin 653:663 neuroserpin 653:663 We used site-directed mutagenesis, transient transfection, western blot, metabolic labelling and ELISA to probe the relationship between glycosylation, folding, polymerisation and degradation of neuroserpin in validated cell models of health and disease. 26367528 3 71 theme validated 668:676 arg1 models 683:688 validated cell models 668:688 validated cell models of health and disease 668:710 We used site-directed mutagenesis, transient transfection, western blot, metabolic labelling and ELISA to probe the relationship between glycosylation, folding, polymerisation and degradation of neuroserpin in validated cell models of health and disease. 26367528 8 72 link N-linked 1606:1613 arg1 events 1629:1634 normal and variant-specific N-linked glycosylation events 1578:1634 normal and variant-specific N-linked glycosylation events 1578:1634 In summary, our results indicate how normal and variant-specific N-linked glycosylation events relate to intracellular folding, misfolding, degradation and polymerisation of neuroserpin. 26367528 4 73 from N157 749:752 arg1 glycosylation 732:744 glycosylation 732:744 glycosylation at N157 and N321 732:761 Our data show that glycosylation at N157 and N321 plays an important role in maintaining the monomeric state of neuroserpin, and we propose this is the result of steric hindrance or effects on local conformational dynamics that can contribute to polymerisation. 26585416 8 0 theme decreased 1086:1094 arg1 affinity 1096:1103 a twofold decreased affinity 1076:1103 a twofold decreased affinity for Gly-Sar 1076:1115 Strikingly, the mutant protein with N50Q exhibited a twofold decreased affinity for Gly-Sar but a 2.5-fold rise in the maximal inward currents compared with the wild-type protein. 26585416 8 1 from rise 1132:1135 arg1 currents 1159:1166 the maximal inward currents 1140:1166 the maximal inward currents 1140:1166 Strikingly, the mutant protein with N50Q exhibited a twofold decreased affinity for Gly-Sar but a 2.5-fold rise in the maximal inward currents compared with the wild-type protein. 26585416 7 2 from levels 997:1002 arg1 membranes 1014:1022 oocyte membranes 1007:1022 oocyte membranes 1007:1022 Electrophysiology revealed all glycosylation-deficient transporters to be functional with comparable expression levels in oocyte membranes. 26585416 10 3 theme C 1334:1334 arg1 -Gly-Sar 1336:1343 [(14)C]-Gly-Sar 1329:1343 [(14)C]-Gly-Sar 1329:1343 Tracer flux studies performed with [(14)C]-Gly-Sar confirmed the reduction in substrate affinity and showed twofold increased maximal transport rates for the N50Q transporter. 26585416 10 3 theme C 1334:1334 arg1 14 1331:1332 14 1331:1332 14 1331:1332 Tracer flux studies performed with [(14)C]-Gly-Sar confirmed the reduction in substrate affinity and showed twofold increased maximal transport rates for the N50Q transporter. 26585416 3 4 theme large 464:468 arg1 intestine 470:478 the large intestine 460:478 the large intestine 460:478 Surprisingly, murine PEPT1 (mPEPT1) has an apparent molecular mass of ∼95 kDa in the small intestine but ∼105 kDa in the large intestine. 26585416 3 5 contain has 379:381 arg1 mPEPT1 371:376 mPEPT1 371:376 mPEPT1 371:376 Surprisingly, murine PEPT1 (mPEPT1) has an apparent molecular mass of ∼95 kDa in the small intestine but ∼105 kDa in the large intestine. 26585416 3 5 contain has 379:381 arg2 mass 405:408 an apparent molecular mass 383:408 an apparent molecular mass of ∼95 kDa in the small intestine 383:442 Surprisingly, murine PEPT1 (mPEPT1) has an apparent molecular mass of ∼95 kDa in the small intestine but ∼105 kDa in the large intestine. 26585416 3 5 contain has 379:381 arg1 PEPT1 364:368 murine PEPT1 357:368 murine PEPT1 (mPEPT1) 357:377 Surprisingly, murine PEPT1 (mPEPT1) has an apparent molecular mass of ∼95 kDa in the small intestine but ∼105 kDa in the large intestine. 26585416 3 5 contain has 379:381 arg2 kDa 453:455 ∼105 kDa 448:455 ∼105 kDa 448:455 Surprisingly, murine PEPT1 (mPEPT1) has an apparent molecular mass of ∼95 kDa in the small intestine but ∼105 kDa in the large intestine. 26585416 5 6 theme site-directed 638:650 arg1 mutagenesis 652:662 site-directed mutagenesis 638:662 site-directed mutagenesis followed by expression in Xenopus laevis oocytes 638:711 Putative N-glycosylation sites of mPEPT1 were altered by site-directed mutagenesis followed by expression in Xenopus laevis oocytes. 26585416 2 7 theme apical 274:279 arg1 membranes 281:289 apical membranes 274:289 apical membranes of enterocytes in small intestine and distal colon 274:340 PEPT1 is a high-capacity and low-affinity solute carrier of the SLC15 family found in apical membranes of enterocytes in small intestine and distal colon. 26585416 11 8 theme protein 1622:1628 arg1 N50Q 1630:1633 the mutant protein N50Q 1611:1633 the mutant protein N50Q 1611:1633 Elimination of individual N-glycosylation sites did not alter membrane expression in oocytes or overall transport characteristics except for the mutant protein N50Q. 26585416 1 9 theme epithelial 170:179 arg1 cells 181:185 epithelial cells 170:185 epithelial cells 170:185 The intestinal peptide transporter PEPT1 provides bulk quantities of amino acids to epithelial cells. 26585416 8 10 theme 2.5-fold 1123:1130 arg1 rise 1132:1135 a 2.5-fold rise 1121:1135 a 2.5-fold rise in the maximal inward currents 1121:1166 Strikingly, the mutant protein with N50Q exhibited a twofold decreased affinity for Gly-Sar but a 2.5-fold rise in the maximal inward currents compared with the wild-type protein. 26585416 6 11 dep positions 760:768 arg1 positions 760:768 positions N50, N406, N439, N510, N515, and N532 760:806 positions N50, N406, N439, N510, N515, and N532 760:806 Replacement of six asparagine residues (N) at positions N50, N406, N439, N510, N515, and N532 by glutamine (Q) resulted in a decrease of the mPEPT1 mass by around 35 kDa. 26585416 6 11 dep positions 760:768 arg1 N50 770:772 N50 770:772 N50 770:772 Replacement of six asparagine residues (N) at positions N50, N406, N439, N510, N515, and N532 by glutamine (Q) resulted in a decrease of the mPEPT1 mass by around 35 kDa. 26585416 6 11 dep positions 760:768 arg1 N515 793:796 N515 793:796 N515 793:796 Replacement of six asparagine residues (N) at positions N50, N406, N439, N510, N515, and N532 by glutamine (Q) resulted in a decrease of the mPEPT1 mass by around 35 kDa. 26585416 6 11 dep positions 760:768 arg1 N406 775:778 N406 775:778 N406 775:778 Replacement of six asparagine residues (N) at positions N50, N406, N439, N510, N515, and N532 by glutamine (Q) resulted in a decrease of the mPEPT1 mass by around 35 kDa. 26585416 6 11 dep positions 760:768 arg1 N439 781:784 N439 781:784 N439 781:784 Replacement of six asparagine residues (N) at positions N50, N406, N439, N510, N515, and N532 by glutamine (Q) resulted in a decrease of the mPEPT1 mass by around 35 kDa. 26585416 6 11 dep positions 760:768 arg1 N532 803:806 N532 803:806 N532 803:806 Replacement of six asparagine residues (N) at positions N50, N406, N439, N510, N515, and N532 by glutamine (Q) resulted in a decrease of the mPEPT1 mass by around 35 kDa. 26585416 8 12 theme wild-type 1186:1194 arg1 protein 1196:1202 the wild-type protein 1182:1202 the wild-type protein 1182:1202 Strikingly, the mutant protein with N50Q exhibited a twofold decreased affinity for Gly-Sar but a 2.5-fold rise in the maximal inward currents compared with the wild-type protein. 26585416 5 13 theme mPEPT1 615:620 arg1 mPEPT1 615:620 mPEPT1 615:620 mPEPT1 615:620 Putative N-glycosylation sites of mPEPT1 were altered by site-directed mutagenesis followed by expression in Xenopus laevis oocytes. 26585416 5 13 theme mPEPT1 615:620 arg1 sites 606:610 Putative N-glycosylation sites 581:610 Putative N-glycosylation sites of mPEPT1 581:620 Putative N-glycosylation sites of mPEPT1 were altered by site-directed mutagenesis followed by expression in Xenopus laevis oocytes. 26585416 11 14 theme sites 1512:1516 arg1 Elimination 1470:1480 Elimination 1470:1480 Elimination of individual N-glycosylation sites 1470:1516 Elimination of individual N-glycosylation sites did not alter membrane expression in oocytes or overall transport characteristics except for the mutant protein N50Q. 26585416 10 15 from reduction 1359:1367 arg1 affinity 1382:1389 substrate affinity 1372:1389 substrate affinity 1372:1389 Tracer flux studies performed with [(14)C]-Gly-Sar confirmed the reduction in substrate affinity and showed twofold increased maximal transport rates for the N50Q transporter. 26585416 11 16 theme individual 1485:1494 arg1 sites 1512:1516 individual N-glycosylation sites 1485:1516 individual N-glycosylation sites 1485:1516 Elimination of individual N-glycosylation sites did not alter membrane expression in oocytes or overall transport characteristics except for the mutant protein N50Q. 26585416 5 17 theme Xenopus 690:696 arg1 oocytes 705:711 Xenopus laevis oocytes 690:711 Xenopus laevis oocytes 690:711 Putative N-glycosylation sites of mPEPT1 were altered by site-directed mutagenesis followed by expression in Xenopus laevis oocytes. 26585416 11 18 from expression 1541:1550 arg1 oocytes 1555:1561 oocytes 1555:1561 oocytes 1555:1561 Elimination of individual N-glycosylation sites did not alter membrane expression in oocytes or overall transport characteristics except for the mutant protein N50Q. 26585416 11 18 from expression 1541:1550 arg1 characteristics 1584:1598 overall transport characteristics 1566:1598 overall transport characteristics 1566:1598 Elimination of individual N-glycosylation sites did not alter membrane expression in oocytes or overall transport characteristics except for the mutant protein N50Q. 26585416 8 19 theme maximal 1144:1150 arg1 currents 1159:1166 the maximal inward currents 1140:1166 the maximal inward currents 1140:1166 Strikingly, the mutant protein with N50Q exhibited a twofold decreased affinity for Gly-Sar but a 2.5-fold rise in the maximal inward currents compared with the wild-type protein. 26585416 12 20 from location 1727:1734 arg1 removal 1697:1703 removal 1697:1703 removal of the glycan at this location 1697:1734 Because transporter surface density was not altered in N50Q, removal of the glycan at this location appears to accelerate the substrate turnover rate. 26585416 2 21 theme solute 230:235 arg1 carrier 237:243 a high-capacity and low-affinity solute carrier 197:243 a high-capacity and low-affinity solute carrier of the SLC15 family found in apical membranes of enterocytes in small intestine and distal colon 197:340 PEPT1 is a high-capacity and low-affinity solute carrier of the SLC15 family found in apical membranes of enterocytes in small intestine and distal colon. 26585416 2 21 theme solute 230:235 arg1 PEPT1 188:192 PEPT1 188:192 PEPT1 188:192 PEPT1 is a high-capacity and low-affinity solute carrier of the SLC15 family found in apical membranes of enterocytes in small intestine and distal colon. 26585416 6 22 theme mPEPT1 855:860 arg1 mass 862:865 the mPEPT1 mass 851:865 the mPEPT1 mass by around 35 kDa 851:882 Replacement of six asparagine residues (N) at positions N50, N406, N439, N510, N515, and N532 by glutamine (Q) resulted in a decrease of the mPEPT1 mass by around 35 kDa. 26585416 7 23 theme expression 986:995 arg1 levels 997:1002 comparable expression levels 975:1002 comparable expression levels in oocyte membranes 975:1022 Electrophysiology revealed all glycosylation-deficient transporters to be functional with comparable expression levels in oocyte membranes. 26585416 7 24 theme glycosylation-deficient 916:938 arg1 transporters 940:951 all glycosylation-deficient transporters 912:951 all glycosylation-deficient transporters 912:951 Electrophysiology revealed all glycosylation-deficient transporters to be functional with comparable expression levels in oocyte membranes. 26585416 2 25 from intestine 315:323 arg1 membranes 281:289 apical membranes 274:289 apical membranes of enterocytes in small intestine and distal colon 274:340 PEPT1 is a high-capacity and low-affinity solute carrier of the SLC15 family found in apical membranes of enterocytes in small intestine and distal colon. 26585416 9 26 theme Elevated 1205:1212 arg1 currents 1232:1239 Elevated maximal transport currents 1205:1239 Elevated maximal transport currents 1205:1239 Elevated maximal transport currents were also recorded for cefadroxil and tri-l-alanine. 26585416 2 27 theme SLC15 252:256 arg1 family 258:263 the SLC15 family 248:263 the SLC15 family found in apical membranes of enterocytes in small intestine and distal colon 248:340 PEPT1 is a high-capacity and low-affinity solute carrier of the SLC15 family found in apical membranes of enterocytes in small intestine and distal colon. 26585416 1 28 theme bulk 136:139 arg1 quantities 141:150 bulk quantities 136:150 bulk quantities of amino acids to epithelial cells 136:185 The intestinal peptide transporter PEPT1 provides bulk quantities of amino acids to epithelial cells. 26585416 2 29 from membranes 281:289 arg1 intestine 315:323 small intestine 309:323 small intestine 309:323 PEPT1 is a high-capacity and low-affinity solute carrier of the SLC15 family found in apical membranes of enterocytes in small intestine and distal colon. 26585416 2 29 from membranes 281:289 arg1 colon 336:340 distal colon 329:340 distal colon 329:340 PEPT1 is a high-capacity and low-affinity solute carrier of the SLC15 family found in apical membranes of enterocytes in small intestine and distal colon. 26585416 12 30 theme glycan 1712:1717 arg1 removal 1697:1703 removal 1697:1703 removal of the glycan at this location 1697:1734 Because transporter surface density was not altered in N50Q, removal of the glycan at this location appears to accelerate the substrate turnover rate. 26585416 9 31 theme transport 1222:1230 arg1 currents 1232:1239 Elevated maximal transport currents 1205:1239 Elevated maximal transport currents 1205:1239 Elevated maximal transport currents were also recorded for cefadroxil and tri-l-alanine. 26585416 2 32 from enterocytes 294:304 arg1 intestine 315:323 small intestine 309:323 small intestine 309:323 PEPT1 is a high-capacity and low-affinity solute carrier of the SLC15 family found in apical membranes of enterocytes in small intestine and distal colon. 26585416 2 32 from enterocytes 294:304 arg1 colon 336:340 distal colon 329:340 distal colon 329:340 PEPT1 is a high-capacity and low-affinity solute carrier of the SLC15 family found in apical membranes of enterocytes in small intestine and distal colon. 26585416 0 33 theme transporter 67:77 arg1 PEPT1 79:83 the peptide transporter PEPT1 55:83 the peptide transporter PEPT1 55:83 Effect of N-glycosylation on the transport activity of the peptide transporter PEPT1. 26585416 1 34 theme acids 161:165 arg1 quantities 141:150 bulk quantities 136:150 bulk quantities of amino acids to epithelial cells 136:185 The intestinal peptide transporter PEPT1 provides bulk quantities of amino acids to epithelial cells. 26585416 0 35 from Effect 0:5 arg1 activity 43:50 the transport activity 29:50 the transport activity of the peptide transporter PEPT1 29:83 Effect of N-glycosylation on the transport activity of the peptide transporter PEPT1. 26585416 10 36 theme increased 1410:1418 arg1 rates 1438:1442 twofold increased maximal transport rates 1402:1442 twofold increased maximal transport rates for the N50Q transporter 1402:1467 Tracer flux studies performed with [(14)C]-Gly-Sar confirmed the reduction in substrate affinity and showed twofold increased maximal transport rates for the N50Q transporter. 26585416 0 37 theme transport 33:41 arg1 activity 43:50 the transport activity 29:50 the transport activity of the peptide transporter PEPT1 29:83 Effect of N-glycosylation on the transport activity of the peptide transporter PEPT1. 26585416 3 38 theme small 428:432 arg1 intestine 434:442 the small intestine 424:442 the small intestine 424:442 Surprisingly, murine PEPT1 (mPEPT1) has an apparent molecular mass of ∼95 kDa in the small intestine but ∼105 kDa in the large intestine. 26585416 0 39 theme N-glycosylation 10:24 arg1 Effect 0:5 Effect 0:5 Effect of N-glycosylation on the transport activity of the peptide transporter PEPT1. 0:84 Effect of N-glycosylation on the transport activity of the peptide transporter PEPT1. 26585416 1 40 theme peptide 101:107 arg1 PEPT1 121:125 The intestinal peptide transporter PEPT1 86:125 The intestinal peptide transporter PEPT1 86:125 The intestinal peptide transporter PEPT1 provides bulk quantities of amino acids to epithelial cells. 26585416 3 41 theme apparent 386:393 arg1 mass 405:408 an apparent molecular mass 383:408 an apparent molecular mass of ∼95 kDa in the small intestine 383:442 Surprisingly, murine PEPT1 (mPEPT1) has an apparent molecular mass of ∼95 kDa in the small intestine but ∼105 kDa in the large intestine. 26585416 4 42 theme protein 516:522 arg1 glycosylation 524:536 mPEPT1 protein glycosylation 509:536 mPEPT1 protein glycosylation 509:536 Here we describe studies on mPEPT1 protein glycosylation and how glycans affect transport function. 26585416 10 43 theme transport 1428:1436 arg1 rates 1438:1442 twofold increased maximal transport rates 1402:1442 twofold increased maximal transport rates for the N50Q transporter 1402:1467 Tracer flux studies performed with [(14)C]-Gly-Sar confirmed the reduction in substrate affinity and showed twofold increased maximal transport rates for the N50Q transporter. 26585416 12 44 theme turnover 1772:1779 arg1 rate 1781:1784 the substrate turnover rate 1758:1784 the substrate turnover rate 1758:1784 Because transporter surface density was not altered in N50Q, removal of the glycan at this location appears to accelerate the substrate turnover rate. 26585416 6 45 from positions 760:768 arg1 residues 744:751 six asparagine residues 729:751 six asparagine residues (N) at positions N50, N406, N439, N510, N515, and N532 729:806 Replacement of six asparagine residues (N) at positions N50, N406, N439, N510, N515, and N532 by glutamine (Q) resulted in a decrease of the mPEPT1 mass by around 35 kDa. 26585416 6 45 from positions 760:768 arg1 Replacement 714:724 Replacement 714:724 Replacement of six asparagine residues (N) at positions N50, N406, N439, N510, N515, and N532 by glutamine (Q) 714:823 Replacement of six asparagine residues (N) at positions N50, N406, N439, N510, N515, and N532 by glutamine (Q) resulted in a decrease of the mPEPT1 mass by around 35 kDa. 26585416 6 45 from positions 760:768 arg1 N 754:754 N 754:754 N 754:754 Replacement of six asparagine residues (N) at positions N50, N406, N439, N510, N515, and N532 by glutamine (Q) resulted in a decrease of the mPEPT1 mass by around 35 kDa. 26585416 10 46 theme Tracer 1294:1299 arg1 studies 1306:1312 Tracer flux studies 1294:1312 Tracer flux studies performed with [(14)C]-Gly-Sar 1294:1343 Tracer flux studies performed with [(14)C]-Gly-Sar confirmed the reduction in substrate affinity and showed twofold increased maximal transport rates for the N50Q transporter. 26585416 8 47 theme mutant 1041:1046 arg1 protein 1048:1054 the mutant protein 1037:1054 the mutant protein with N50Q 1037:1064 Strikingly, the mutant protein with N50Q exhibited a twofold decreased affinity for Gly-Sar but a 2.5-fold rise in the maximal inward currents compared with the wild-type protein. 26585416 10 48 theme N50Q 1452:1455 arg1 transporter 1457:1467 the N50Q transporter 1448:1467 the N50Q transporter 1448:1467 Tracer flux studies performed with [(14)C]-Gly-Sar confirmed the reduction in substrate affinity and showed twofold increased maximal transport rates for the N50Q transporter. 26585416 6 49 theme asparagine 733:742 arg1 residues 744:751 six asparagine residues 729:751 six asparagine residues (N) at positions N50, N406, N439, N510, N515, and N532 729:806 Replacement of six asparagine residues (N) at positions N50, N406, N439, N510, N515, and N532 by glutamine (Q) resulted in a decrease of the mPEPT1 mass by around 35 kDa. 26585416 6 49 theme asparagine 733:742 arg1 N 754:754 N 754:754 N 754:754 Replacement of six asparagine residues (N) at positions N50, N406, N439, N510, N515, and N532 by glutamine (Q) resulted in a decrease of the mPEPT1 mass by around 35 kDa. 26585416 4 50 theme transport 561:569 arg1 function 571:578 transport function 561:578 transport function 561:578 Here we describe studies on mPEPT1 protein glycosylation and how glycans affect transport function. 26585416 12 51 theme surface 1656:1662 arg1 density 1664:1670 transporter surface density 1644:1670 transporter surface density 1644:1670 Because transporter surface density was not altered in N50Q, removal of the glycan at this location appears to accelerate the substrate turnover rate. 26585416 11 52 theme mutant 1615:1620 arg1 N50Q 1630:1633 the mutant protein N50Q 1611:1633 the mutant protein N50Q 1611:1633 Elimination of individual N-glycosylation sites did not alter membrane expression in oocytes or overall transport characteristics except for the mutant protein N50Q. 26585416 11 53 theme overall 1566:1572 arg1 characteristics 1584:1598 overall transport characteristics 1566:1598 overall transport characteristics 1566:1598 Elimination of individual N-glycosylation sites did not alter membrane expression in oocytes or overall transport characteristics except for the mutant protein N50Q. 26585416 8 54 with protein 1048:1054 arg1 N50Q 1061:1064 N50Q 1061:1064 N50Q 1061:1064 Strikingly, the mutant protein with N50Q exhibited a twofold decreased affinity for Gly-Sar but a 2.5-fold rise in the maximal inward currents compared with the wild-type protein. 26585416 11 55 theme N-glycosylation 1496:1510 arg1 sites 1512:1516 individual N-glycosylation sites 1485:1516 individual N-glycosylation sites 1485:1516 Elimination of individual N-glycosylation sites did not alter membrane expression in oocytes or overall transport characteristics except for the mutant protein N50Q. 26585416 2 56 from colon 336:340 arg1 membranes 281:289 apical membranes 274:289 apical membranes of enterocytes in small intestine and distal colon 274:340 PEPT1 is a high-capacity and low-affinity solute carrier of the SLC15 family found in apical membranes of enterocytes in small intestine and distal colon. 26585416 5 57 theme N-glycosylation 590:604 arg1 mPEPT1 615:620 mPEPT1 615:620 mPEPT1 615:620 Putative N-glycosylation sites of mPEPT1 were altered by site-directed mutagenesis followed by expression in Xenopus laevis oocytes. 26585416 5 57 theme N-glycosylation 590:604 arg1 sites 606:610 Putative N-glycosylation sites 581:610 Putative N-glycosylation sites of mPEPT1 581:620 Putative N-glycosylation sites of mPEPT1 were altered by site-directed mutagenesis followed by expression in Xenopus laevis oocytes. 26585416 3 58 from mass 405:408 arg1 intestine 434:442 the small intestine 424:442 the small intestine 424:442 Surprisingly, murine PEPT1 (mPEPT1) has an apparent molecular mass of ∼95 kDa in the small intestine but ∼105 kDa in the large intestine. 26585416 2 59 theme small 309:313 arg1 intestine 315:323 small intestine 309:323 small intestine 309:323 PEPT1 is a high-capacity and low-affinity solute carrier of the SLC15 family found in apical membranes of enterocytes in small intestine and distal colon. 26585416 7 60 theme oocyte 1007:1012 arg1 membranes 1014:1022 oocyte membranes 1007:1022 oocyte membranes 1007:1022 Electrophysiology revealed all glycosylation-deficient transporters to be functional with comparable expression levels in oocyte membranes. 26585416 2 61 theme enterocytes 294:304 arg1 membranes 281:289 apical membranes 274:289 apical membranes of enterocytes in small intestine and distal colon 274:340 PEPT1 is a high-capacity and low-affinity solute carrier of the SLC15 family found in apical membranes of enterocytes in small intestine and distal colon. 26585416 11 62 theme membrane 1532:1539 arg1 expression 1541:1550 membrane expression 1532:1550 membrane expression in oocytes or overall transport characteristics 1532:1598 Elimination of individual N-glycosylation sites did not alter membrane expression in oocytes or overall transport characteristics except for the mutant protein N50Q. 26585416 5 63 gly N-glycosylation 590:604 arg1 mPEPT1 615:620 mPEPT1 615:620 mPEPT1 615:620 Putative N-glycosylation sites of mPEPT1 were altered by site-directed mutagenesis followed by expression in Xenopus laevis oocytes. 26585416 5 63 gly N-glycosylation 590:604 arg2 mPEPT1 615:620 mPEPT1 615:620 mPEPT1 615:620 Putative N-glycosylation sites of mPEPT1 were altered by site-directed mutagenesis followed by expression in Xenopus laevis oocytes. 26585416 5 63 gly N-glycosylation 590:604 arg2 sites 606:610 Putative N-glycosylation sites 581:610 Putative N-glycosylation sites of mPEPT1 581:620 Putative N-glycosylation sites of mPEPT1 were altered by site-directed mutagenesis followed by expression in Xenopus laevis oocytes. 26585416 5 64 theme laevis 698:703 arg1 oocytes 705:711 Xenopus laevis oocytes 690:711 Xenopus laevis oocytes 690:711 Putative N-glycosylation sites of mPEPT1 were altered by site-directed mutagenesis followed by expression in Xenopus laevis oocytes. 26585416 6 65 theme mass 862:865 arg1 decrease 839:846 a decrease 837:846 a decrease of the mPEPT1 mass by around 35 kDa 837:882 Replacement of six asparagine residues (N) at positions N50, N406, N439, N510, N515, and N532 by glutamine (Q) resulted in a decrease of the mPEPT1 mass by around 35 kDa. 26585416 7 66 theme comparable 975:984 arg1 levels 997:1002 comparable expression levels 975:1002 comparable expression levels in oocyte membranes 975:1022 Electrophysiology revealed all glycosylation-deficient transporters to be functional with comparable expression levels in oocyte membranes. 26585416 2 67 theme low-affinity 217:228 arg1 carrier 237:243 a high-capacity and low-affinity solute carrier 197:243 a high-capacity and low-affinity solute carrier of the SLC15 family found in apical membranes of enterocytes in small intestine and distal colon 197:340 PEPT1 is a high-capacity and low-affinity solute carrier of the SLC15 family found in apical membranes of enterocytes in small intestine and distal colon. 26585416 2 67 theme low-affinity 217:228 arg1 PEPT1 188:192 PEPT1 188:192 PEPT1 188:192 PEPT1 is a high-capacity and low-affinity solute carrier of the SLC15 family found in apical membranes of enterocytes in small intestine and distal colon. 26585416 1 68 theme transporter 109:119 arg1 PEPT1 121:125 The intestinal peptide transporter PEPT1 86:125 The intestinal peptide transporter PEPT1 86:125 The intestinal peptide transporter PEPT1 provides bulk quantities of amino acids to epithelial cells. 26585416 8 69 theme inward 1152:1157 arg1 currents 1159:1166 the maximal inward currents 1140:1166 the maximal inward currents 1140:1166 Strikingly, the mutant protein with N50Q exhibited a twofold decreased affinity for Gly-Sar but a 2.5-fold rise in the maximal inward currents compared with the wild-type protein. 26585416 2 70 theme family 258:263 arg1 carrier 237:243 a high-capacity and low-affinity solute carrier 197:243 a high-capacity and low-affinity solute carrier of the SLC15 family found in apical membranes of enterocytes in small intestine and distal colon 197:340 PEPT1 is a high-capacity and low-affinity solute carrier of the SLC15 family found in apical membranes of enterocytes in small intestine and distal colon. 26585416 2 70 theme family 258:263 arg1 PEPT1 188:192 PEPT1 188:192 PEPT1 188:192 PEPT1 is a high-capacity and low-affinity solute carrier of the SLC15 family found in apical membranes of enterocytes in small intestine and distal colon. 26585416 0 71 theme peptide 59:65 arg1 PEPT1 79:83 the peptide transporter PEPT1 55:83 the peptide transporter PEPT1 55:83 Effect of N-glycosylation on the transport activity of the peptide transporter PEPT1. 26585416 9 72 theme maximal 1214:1220 arg1 currents 1232:1239 Elevated maximal transport currents 1205:1239 Elevated maximal transport currents 1205:1239 Elevated maximal transport currents were also recorded for cefadroxil and tri-l-alanine. 26585416 0 73 theme PEPT1 79:83 arg1 activity 43:50 the transport activity 29:50 the transport activity of the peptide transporter PEPT1 29:83 Effect of N-glycosylation on the transport activity of the peptide transporter PEPT1. 26585416 4 74 dep describe 489:496 arg1 affect 554:559 affect 554:559 affect transport function 554:578 Here we describe studies on mPEPT1 protein glycosylation and how glycans affect transport function. 26585416 1 75 theme amino 155:159 arg1 acids 161:165 amino acids 155:165 amino acids 155:165 The intestinal peptide transporter PEPT1 provides bulk quantities of amino acids to epithelial cells. 26585416 12 76 theme transporter 1644:1654 arg1 density 1664:1670 transporter surface density 1644:1670 transporter surface density 1644:1670 Because transporter surface density was not altered in N50Q, removal of the glycan at this location appears to accelerate the substrate turnover rate. 26585416 10 77 theme substrate 1372:1380 arg1 affinity 1382:1389 substrate affinity 1372:1389 substrate affinity 1372:1389 Tracer flux studies performed with [(14)C]-Gly-Sar confirmed the reduction in substrate affinity and showed twofold increased maximal transport rates for the N50Q transporter. 26585416 12 78 attach removal 1697:1703 arg3 location 1727:1734 this location 1722:1734 this location 1722:1734 Because transporter surface density was not altered in N50Q, removal of the glycan at this location appears to accelerate the substrate turnover rate. 26585416 12 78 attach removal 1697:1703 arg2 glycan 1712:1717 the glycan 1708:1717 the glycan 1708:1717 Because transporter surface density was not altered in N50Q, removal of the glycan at this location appears to accelerate the substrate turnover rate. 26585416 11 79 gly N-glycosylation 1496:1510 arg2 sites 1512:1516 individual N-glycosylation sites 1485:1516 individual N-glycosylation sites 1485:1516 Elimination of individual N-glycosylation sites did not alter membrane expression in oocytes or overall transport characteristics except for the mutant protein N50Q. 26585416 3 80 theme murine 357:362 arg1 mPEPT1 371:376 mPEPT1 371:376 mPEPT1 371:376 Surprisingly, murine PEPT1 (mPEPT1) has an apparent molecular mass of ∼95 kDa in the small intestine but ∼105 kDa in the large intestine. 26585416 3 80 theme murine 357:362 arg1 PEPT1 364:368 murine PEPT1 357:368 murine PEPT1 (mPEPT1) 357:377 Surprisingly, murine PEPT1 (mPEPT1) has an apparent molecular mass of ∼95 kDa in the small intestine but ∼105 kDa in the large intestine. 26585416 5 81 theme Putative 581:588 arg1 mPEPT1 615:620 mPEPT1 615:620 mPEPT1 615:620 Putative N-glycosylation sites of mPEPT1 were altered by site-directed mutagenesis followed by expression in Xenopus laevis oocytes. 26585416 5 81 theme Putative 581:588 arg1 sites 606:610 Putative N-glycosylation sites 581:610 Putative N-glycosylation sites of mPEPT1 581:620 Putative N-glycosylation sites of mPEPT1 were altered by site-directed mutagenesis followed by expression in Xenopus laevis oocytes. 26585416 7 82 with functional 959:968 arg1 levels 997:1002 comparable expression levels 975:1002 comparable expression levels in oocyte membranes 975:1022 Electrophysiology revealed all glycosylation-deficient transporters to be functional with comparable expression levels in oocyte membranes. 26585416 3 83 theme kDa 417:419 arg1 mass 405:408 an apparent molecular mass 383:408 an apparent molecular mass of ∼95 kDa in the small intestine 383:442 Surprisingly, murine PEPT1 (mPEPT1) has an apparent molecular mass of ∼95 kDa in the small intestine but ∼105 kDa in the large intestine. 26585416 4 84 theme mPEPT1 509:514 arg1 glycosylation 524:536 mPEPT1 protein glycosylation 509:536 mPEPT1 protein glycosylation 509:536 Here we describe studies on mPEPT1 protein glycosylation and how glycans affect transport function. 26585416 1 85 theme intestinal 90:99 arg1 PEPT1 121:125 The intestinal peptide transporter PEPT1 86:125 The intestinal peptide transporter PEPT1 86:125 The intestinal peptide transporter PEPT1 provides bulk quantities of amino acids to epithelial cells. 26585416 4 86 from studies 498:504 arg1 glycosylation 524:536 mPEPT1 protein glycosylation 509:536 mPEPT1 protein glycosylation 509:536 Here we describe studies on mPEPT1 protein glycosylation and how glycans affect transport function. 26585416 3 87 theme molecular 395:403 arg1 mass 405:408 an apparent molecular mass 383:408 an apparent molecular mass of ∼95 kDa in the small intestine 383:442 Surprisingly, murine PEPT1 (mPEPT1) has an apparent molecular mass of ∼95 kDa in the small intestine but ∼105 kDa in the large intestine. 26585416 10 88 theme maximal 1420:1426 arg1 rates 1438:1442 twofold increased maximal transport rates 1402:1442 twofold increased maximal transport rates for the N50Q transporter 1402:1467 Tracer flux studies performed with [(14)C]-Gly-Sar confirmed the reduction in substrate affinity and showed twofold increased maximal transport rates for the N50Q transporter. 26585416 10 89 theme flux 1301:1304 arg1 studies 1306:1312 Tracer flux studies 1294:1312 Tracer flux studies performed with [(14)C]-Gly-Sar 1294:1343 Tracer flux studies performed with [(14)C]-Gly-Sar confirmed the reduction in substrate affinity and showed twofold increased maximal transport rates for the N50Q transporter. 26585416 0 90 gly N-glycosylation 10:24 arg1 transport 33:41 the transport activity 29:50 the transport activity of the peptide transporter PEPT1 29:83 Effect of N-glycosylation on the transport activity of the peptide transporter PEPT1. 26585416 0 90 gly N-glycosylation 10:24 arg1 PEPT1 79:83 the peptide transporter PEPT1 55:83 the peptide transporter PEPT1 55:83 Effect of N-glycosylation on the transport activity of the peptide transporter PEPT1. 26585416 12 91 theme substrate 1762:1770 arg1 rate 1781:1784 the substrate turnover rate 1758:1784 the substrate turnover rate 1758:1784 Because transporter surface density was not altered in N50Q, removal of the glycan at this location appears to accelerate the substrate turnover rate. 26585416 2 92 located found 265:269 arg2 family 258:263 the SLC15 family 248:263 the SLC15 family found in apical membranes of enterocytes in small intestine and distal colon 248:340 PEPT1 is a high-capacity and low-affinity solute carrier of the SLC15 family found in apical membranes of enterocytes in small intestine and distal colon. 26585416 2 92 located found 265:269 arg1 membranes 281:289 apical membranes 274:289 apical membranes of enterocytes in small intestine and distal colon 274:340 PEPT1 is a high-capacity and low-affinity solute carrier of the SLC15 family found in apical membranes of enterocytes in small intestine and distal colon. 26585416 2 93 theme high-capacity 199:211 arg1 carrier 237:243 a high-capacity and low-affinity solute carrier 197:243 a high-capacity and low-affinity solute carrier of the SLC15 family found in apical membranes of enterocytes in small intestine and distal colon 197:340 PEPT1 is a high-capacity and low-affinity solute carrier of the SLC15 family found in apical membranes of enterocytes in small intestine and distal colon. 26585416 2 93 theme high-capacity 199:211 arg1 PEPT1 188:192 PEPT1 188:192 PEPT1 188:192 PEPT1 is a high-capacity and low-affinity solute carrier of the SLC15 family found in apical membranes of enterocytes in small intestine and distal colon. 26585416 6 94 theme residues 744:751 arg1 Replacement 714:724 Replacement 714:724 Replacement of six asparagine residues (N) at positions N50, N406, N439, N510, N515, and N532 by glutamine (Q) 714:823 Replacement of six asparagine residues (N) at positions N50, N406, N439, N510, N515, and N532 by glutamine (Q) resulted in a decrease of the mPEPT1 mass by around 35 kDa. 26585416 2 95 theme distal 329:334 arg1 colon 336:340 distal colon 329:340 distal colon 329:340 PEPT1 is a high-capacity and low-affinity solute carrier of the SLC15 family found in apical membranes of enterocytes in small intestine and distal colon. 26585416 11 96 theme transport 1574:1582 arg1 characteristics 1584:1598 overall transport characteristics 1566:1598 overall transport characteristics 1566:1598 Elimination of individual N-glycosylation sites did not alter membrane expression in oocytes or overall transport characteristics except for the mutant protein N50Q. 26585416 5 97 from expression 676:685 arg1 oocytes 705:711 Xenopus laevis oocytes 690:711 Xenopus laevis oocytes 690:711 Putative N-glycosylation sites of mPEPT1 were altered by site-directed mutagenesis followed by expression in Xenopus laevis oocytes. 26585416 6 98 from Replacement 714:724 arg1 positions 760:768 positions N50, N406, N439, N510, N515, and N532 760:806 positions N50, N406, N439, N510, N515, and N532 760:806 Replacement of six asparagine residues (N) at positions N50, N406, N439, N510, N515, and N532 by glutamine (Q) resulted in a decrease of the mPEPT1 mass by around 35 kDa. 26585416 6 98 from Replacement 714:724 arg1 N50 770:772 N50 770:772 N50 770:772 Replacement of six asparagine residues (N) at positions N50, N406, N439, N510, N515, and N532 by glutamine (Q) resulted in a decrease of the mPEPT1 mass by around 35 kDa. 26585416 6 98 from Replacement 714:724 arg1 N515 793:796 N515 793:796 N515 793:796 Replacement of six asparagine residues (N) at positions N50, N406, N439, N510, N515, and N532 by glutamine (Q) resulted in a decrease of the mPEPT1 mass by around 35 kDa. 26585416 6 98 from Replacement 714:724 arg1 N406 775:778 N406 775:778 N406 775:778 Replacement of six asparagine residues (N) at positions N50, N406, N439, N510, N515, and N532 by glutamine (Q) resulted in a decrease of the mPEPT1 mass by around 35 kDa. 26585416 6 98 from Replacement 714:724 arg1 N439 781:784 N439 781:784 N439 781:784 Replacement of six asparagine residues (N) at positions N50, N406, N439, N510, N515, and N532 by glutamine (Q) resulted in a decrease of the mPEPT1 mass by around 35 kDa. 26585416 6 98 from Replacement 714:724 arg1 N532 803:806 N532 803:806 N532 803:806 Replacement of six asparagine residues (N) at positions N50, N406, N439, N510, N515, and N532 by glutamine (Q) resulted in a decrease of the mPEPT1 mass by around 35 kDa. 27612916 7 0 from formation 1438:1446 arg1 decrease 1407:1414 a significant decrease 1393:1414 a significant decrease of 49% and 40% in the formation of zidovudine and mycophenolic acid glucuronides, respectively 1393:1509 The presence of an additional N-linked glycan on the UGT2B7 enzyme, likely affecting proper protein folding, resulted in a significant decrease of 49% and 40% in the formation of zidovudine and mycophenolic acid glucuronides, respectively. 27612916 7 1 theme % 1429:1429 arg1 decrease 1407:1414 a significant decrease 1393:1414 a significant decrease of 49% and 40% in the formation of zidovudine and mycophenolic acid glucuronides, respectively 1393:1509 The presence of an additional N-linked glycan on the UGT2B7 enzyme, likely affecting proper protein folding, resulted in a significant decrease of 49% and 40% in the formation of zidovudine and mycophenolic acid glucuronides, respectively. 27612916 6 2 theme N-glycosylation 1037:1051 arg1 motif 1053:1057 a putative N-glycosylation motif NX(S/T) 1026:1065 a putative N-glycosylation motif NX(S/T) subsequently validated upon endoglycosidase H treatment of microsomal fractions and inhibition of N-glycosylation of endogenously produced UGT2B7 with tunicamycin in human embryonic kidney (HEK293) cells 1026:1269 This amino acid change was predicted to create a putative N-glycosylation motif NX(S/T) subsequently validated upon endoglycosidase H treatment of microsomal fractions and inhibition of N-glycosylation of endogenously produced UGT2B7 with tunicamycin in human embryonic kidney (HEK293) cells. 27612916 3 3 theme rare 484:487 arg1 % 511:511 frequency <1% 499:511 frequency <1% 499:511 Most studies currently survey common variants and examine only a small fraction of the genetic diversity; however, rare variants (frequency <1%) might have a significant effect because they are predicted to greatly outnumber common variants in the human genome. 27612916 3 3 theme rare 484:487 arg1 variants 489:496 rare variants 484:496 rare variants (frequency <1%) 484:512 Most studies currently survey common variants and examine only a small fraction of the genetic diversity; however, rare variants (frequency <1%) might have a significant effect because they are predicted to greatly outnumber common variants in the human genome. 27612916 9 4 link N-linked 1879:1886 arg1 glycosylation 1888:1900 N-linked glycosylation 1879:1900 N-linked glycosylation with consequences on drug metabolism 1879:1937 Collectively, these variants have the potential to increase the proportion of variance explained in the UGT pathway resulting from changes in PTMs, such as N-linked glycosylation with consequences on drug metabolism. 27612916 6 5 theme fractions 1137:1145 arg1 treatment 1113:1121 endoglycosidase H treatment 1095:1121 endoglycosidase H treatment of microsomal fractions and inhibition of N-glycosylation of endogenously produced UGT2B7 with tunicamycin in human embryonic kidney (HEK293) cells 1095:1269 This amino acid change was predicted to create a putative N-glycosylation motif NX(S/T) subsequently validated upon endoglycosidase H treatment of microsomal fractions and inhibition of N-glycosylation of endogenously produced UGT2B7 with tunicamycin in human embryonic kidney (HEK293) cells. 27612916 8 6 theme rare 1586:1589 arg1 variations 1621:1630 32 rare, naturally occurring missense variations 1583:1630 32 rare, naturally occurring missense variations predicted to create or disrupt N-glycosylation sequence motifs in the other UGT2B enzymes 1583:1720 A systematic survey of the Short Genetic Variations database uncovered 32 rare, naturally occurring missense variations predicted to create or disrupt N-glycosylation sequence motifs in the other UGT2B enzymes. 27612916 3 7 from variants 601:608 arg1 genome 623:628 the human genome 613:628 the human genome 613:628 Most studies currently survey common variants and examine only a small fraction of the genetic diversity; however, rare variants (frequency <1%) might have a significant effect because they are predicted to greatly outnumber common variants in the human genome. 27612916 6 8 theme embryonic 1239:1247 arg1 kidney 1249:1254 human embryonic kidney 1233:1254 human embryonic kidney (HEK293) cells 1233:1269 This amino acid change was predicted to create a putative N-glycosylation motif NX(S/T) subsequently validated upon endoglycosidase H treatment of microsomal fractions and inhibition of N-glycosylation of endogenously produced UGT2B7 with tunicamycin in human embryonic kidney (HEK293) cells. 27612916 6 8 theme embryonic 1239:1247 arg1 HEK293 1257:1262 HEK293 1257:1262 HEK293 1257:1262 This amino acid change was predicted to create a putative N-glycosylation motif NX(S/T) subsequently validated upon endoglycosidase H treatment of microsomal fractions and inhibition of N-glycosylation of endogenously produced UGT2B7 with tunicamycin in human embryonic kidney (HEK293) cells. 27612916 2 9 from action 334:339 arg1 drugs 362:366 drugs 362:366 drugs 362:366 UGT2B7 is of particular interest because of its action on a wide variety of drugs. 27612916 2 9 from action 334:339 arg1 variety 351:357 a wide variety 344:357 a wide variety of drugs 344:366 UGT2B7 is of particular interest because of its action on a wide variety of drugs. 27612916 8 10 theme sequence 1679:1686 arg1 motifs 1688:1693 N-glycosylation sequence motifs 1663:1693 N-glycosylation sequence motifs in the other UGT2B enzymes 1663:1720 A systematic survey of the Short Genetic Variations database uncovered 32 rare, naturally occurring missense variations predicted to create or disrupt N-glycosylation sequence motifs in the other UGT2B enzymes. 27612916 7 11 theme protein 1364:1370 arg1 folding 1372:1378 proper protein folding 1357:1378 proper protein folding 1357:1378 The presence of an additional N-linked glycan on the UGT2B7 enzyme, likely affecting proper protein folding, resulted in a significant decrease of 49% and 40% in the formation of zidovudine and mycophenolic acid glucuronides, respectively. 27612916 3 12 theme significant 527:537 arg1 effect 539:544 a significant effect 525:544 a significant effect 525:544 Most studies currently survey common variants and examine only a small fraction of the genetic diversity; however, rare variants (frequency <1%) might have a significant effect because they are predicted to greatly outnumber common variants in the human genome. 27612916 9 13 theme N-linked 1879:1886 arg1 glycosylation 1888:1900 N-linked glycosylation 1879:1900 N-linked glycosylation with consequences on drug metabolism 1879:1937 Collectively, these variants have the potential to increase the proportion of variance explained in the UGT pathway resulting from changes in PTMs, such as N-linked glycosylation with consequences on drug metabolism. 27612916 8 14 theme other 1702:1706 arg1 enzymes 1714:1720 the other UGT2B enzymes 1698:1720 the other UGT2B enzymes 1698:1720 A systematic survey of the Short Genetic Variations database uncovered 32 rare, naturally occurring missense variations predicted to create or disrupt N-glycosylation sequence motifs in the other UGT2B enzymes. 27612916 7 15 from % 1421:1421 arg1 formation 1438:1446 the formation 1434:1446 the formation of zidovudine and mycophenolic acid glucuronides 1434:1495 The presence of an additional N-linked glycan on the UGT2B7 enzyme, likely affecting proper protein folding, resulted in a significant decrease of 49% and 40% in the formation of zidovudine and mycophenolic acid glucuronides, respectively. 27612916 8 16 gly N-glycosylation 1663:1677 arg2 motifs 1688:1693 N-glycosylation sequence motifs 1663:1693 N-glycosylation sequence motifs in the other UGT2B enzymes 1663:1720 A systematic survey of the Short Genetic Variations database uncovered 32 rare, naturally occurring missense variations predicted to create or disrupt N-glycosylation sequence motifs in the other UGT2B enzymes. 27612916 0 17 from Codon 62:66 arg1 Site 54:57 a Novel N-Glycosylation Site 30:57 a Novel N-Glycosylation Site at Codon 121 with Impaired Enzyme Activity 30:100 A Rare UGT2B7 Variant Creates a Novel N-Glycosylation Site at Codon 121 with Impaired Enzyme Activity. 27612916 6 18 theme UGT2B7 1206:1211 arg1 N-glycosylation 1165:1179 N-glycosylation 1165:1179 N-glycosylation of endogenously produced UGT2B7 with tunicamycin in human embryonic kidney (HEK293) cells 1165:1269 This amino acid change was predicted to create a putative N-glycosylation motif NX(S/T) subsequently validated upon endoglycosidase H treatment of microsomal fractions and inhibition of N-glycosylation of endogenously produced UGT2B7 with tunicamycin in human embryonic kidney (HEK293) cells. 27612916 1 19 theme reticulum 208:216 arg1 membranes 218:226 the endoplasmic reticulum membranes 192:226 the endoplasmic reticulum membranes 192:226 The UDP glucuronosyltransferase (UGT) superfamily comprises glycoproteins that reside in the endoplasmic reticulum membranes and that undergo post-translational modifications (PTMs). 27612916 7 20 theme UGT2B7 1325:1330 arg1 enzyme 1332:1337 the UGT2B7 enzyme 1321:1337 the UGT2B7 enzyme 1321:1337 The presence of an additional N-linked glycan on the UGT2B7 enzyme, likely affecting proper protein folding, resulted in a significant decrease of 49% and 40% in the formation of zidovudine and mycophenolic acid glucuronides, respectively. 27612916 4 21 theme UGT2B7 670:675 arg1 variant 677:683 a rare single nucleotide UGT2B7 variant 645:683 a rare single nucleotide UGT2B7 variant of potential pharmacogenetic relevance that encodes a nonconservative amino acid substitution at codon 121 645:790 We discovered a rare single nucleotide UGT2B7 variant of potential pharmacogenetic relevance that encodes a nonconservative amino acid substitution at codon 121. 27612916 4 21 theme UGT2B7 670:675 arg1 substitution 766:777 a nonconservative amino acid substitution 737:777 a nonconservative amino acid substitution at codon 121 737:790 We discovered a rare single nucleotide UGT2B7 variant of potential pharmacogenetic relevance that encodes a nonconservative amino acid substitution at codon 121. 27612916 6 22 theme N-glycosylation 1165:1179 arg1 inhibition 1151:1160 inhibition 1151:1160 inhibition of N-glycosylation of endogenously produced UGT2B7 with tunicamycin in human embryonic kidney (HEK293) cells 1151:1269 This amino acid change was predicted to create a putative N-glycosylation motif NX(S/T) subsequently validated upon endoglycosidase H treatment of microsomal fractions and inhibition of N-glycosylation of endogenously produced UGT2B7 with tunicamycin in human embryonic kidney (HEK293) cells. 27612916 6 22 theme N-glycosylation 1165:1179 arg1 fractions 1137:1145 microsomal fractions 1126:1145 microsomal fractions 1126:1145 This amino acid change was predicted to create a putative N-glycosylation motif NX(S/T) subsequently validated upon endoglycosidase H treatment of microsomal fractions and inhibition of N-glycosylation of endogenously produced UGT2B7 with tunicamycin in human embryonic kidney (HEK293) cells. 27612916 4 23 from codon 782:786 arg1 variant 677:683 a rare single nucleotide UGT2B7 variant 645:683 a rare single nucleotide UGT2B7 variant of potential pharmacogenetic relevance that encodes a nonconservative amino acid substitution at codon 121 645:790 We discovered a rare single nucleotide UGT2B7 variant of potential pharmacogenetic relevance that encodes a nonconservative amino acid substitution at codon 121. 27612916 4 23 from codon 782:786 arg1 substitution 766:777 a nonconservative amino acid substitution 737:777 a nonconservative amino acid substitution at codon 121 737:790 We discovered a rare single nucleotide UGT2B7 variant of potential pharmacogenetic relevance that encodes a nonconservative amino acid substitution at codon 121. 27612916 1 24 theme glucuronosyltransferase 111:133 arg1 superfamily 141:151 The UDP glucuronosyltransferase (UGT) superfamily 103:151 The UDP glucuronosyltransferase (UGT) superfamily 103:151 The UDP glucuronosyltransferase (UGT) superfamily comprises glycoproteins that reside in the endoplasmic reticulum membranes and that undergo post-translational modifications (PTMs). 27612916 7 25 theme N-linked 1302:1309 arg1 glycan 1311:1316 an additional N-linked glycan 1288:1316 an additional N-linked glycan on the UGT2B7 enzyme 1288:1337 The presence of an additional N-linked glycan on the UGT2B7 enzyme, likely affecting proper protein folding, resulted in a significant decrease of 49% and 40% in the formation of zidovudine and mycophenolic acid glucuronides, respectively. 27612916 8 26 dep rare 1586:1589 arg1 occurring 1602:1610 occurring 1602:1610 occurring 1602:1610 A systematic survey of the Short Genetic Variations database uncovered 32 rare, naturally occurring missense variations predicted to create or disrupt N-glycosylation sequence motifs in the other UGT2B enzymes. 27612916 5 27 theme low-frequency 798:810 arg1 variation 812:820 This low-frequency variation 793:820 This low-frequency variation 793:820 This low-frequency variation, found in two individuals of a population of 305 healthy volunteers, leads to the translation of an asparagine instead of an aspartic acid (UGT2B7 p.D121N). 27612916 4 28 theme single 652:657 arg1 variant 677:683 a rare single nucleotide UGT2B7 variant 645:683 a rare single nucleotide UGT2B7 variant of potential pharmacogenetic relevance that encodes a nonconservative amino acid substitution at codon 121 645:790 We discovered a rare single nucleotide UGT2B7 variant of potential pharmacogenetic relevance that encodes a nonconservative amino acid substitution at codon 121. 27612916 4 28 theme single 652:657 arg1 substitution 766:777 a nonconservative amino acid substitution 737:777 a nonconservative amino acid substitution at codon 121 737:790 We discovered a rare single nucleotide UGT2B7 variant of potential pharmacogenetic relevance that encodes a nonconservative amino acid substitution at codon 121. 27612916 5 29 theme healthy 871:877 arg1 volunteers 879:888 305 healthy volunteers 867:888 305 healthy volunteers 867:888 This low-frequency variation, found in two individuals of a population of 305 healthy volunteers, leads to the translation of an asparagine instead of an aspartic acid (UGT2B7 p.D121N). 27612916 9 30 from changes 1854:1860 arg1 glycosylation 1888:1900 N-linked glycosylation 1879:1900 N-linked glycosylation with consequences on drug metabolism 1879:1937 Collectively, these variants have the potential to increase the proportion of variance explained in the UGT pathway resulting from changes in PTMs, such as N-linked glycosylation with consequences on drug metabolism. 27612916 9 30 from changes 1854:1860 arg1 PTMs 1865:1868 PTMs 1865:1868 PTMs 1865:1868 Collectively, these variants have the potential to increase the proportion of variance explained in the UGT pathway resulting from changes in PTMs, such as N-linked glycosylation with consequences on drug metabolism. 27612916 4 31 theme amino 755:759 arg1 variant 677:683 a rare single nucleotide UGT2B7 variant 645:683 a rare single nucleotide UGT2B7 variant of potential pharmacogenetic relevance that encodes a nonconservative amino acid substitution at codon 121 645:790 We discovered a rare single nucleotide UGT2B7 variant of potential pharmacogenetic relevance that encodes a nonconservative amino acid substitution at codon 121. 27612916 4 31 theme amino 755:759 arg1 substitution 766:777 a nonconservative amino acid substitution 737:777 a nonconservative amino acid substitution at codon 121 737:790 We discovered a rare single nucleotide UGT2B7 variant of potential pharmacogenetic relevance that encodes a nonconservative amino acid substitution at codon 121. 27612916 0 32 theme Enzyme 86:91 arg1 Activity 93:100 Impaired Enzyme Activity 77:100 Impaired Enzyme Activity 77:100 A Rare UGT2B7 Variant Creates a Novel N-Glycosylation Site at Codon 121 with Impaired Enzyme Activity. 27612916 7 33 theme additional 1291:1300 arg1 glycan 1311:1316 an additional N-linked glycan 1288:1316 an additional N-linked glycan on the UGT2B7 enzyme 1288:1337 The presence of an additional N-linked glycan on the UGT2B7 enzyme, likely affecting proper protein folding, resulted in a significant decrease of 49% and 40% in the formation of zidovudine and mycophenolic acid glucuronides, respectively. 27612916 7 34 link N-linked 1302:1309 arg1 glycan 1311:1316 an additional N-linked glycan 1288:1316 an additional N-linked glycan on the UGT2B7 enzyme 1288:1337 The presence of an additional N-linked glycan on the UGT2B7 enzyme, likely affecting proper protein folding, resulted in a significant decrease of 49% and 40% in the formation of zidovudine and mycophenolic acid glucuronides, respectively. 27612916 4 35 theme pharmacogenetic 698:712 arg1 relevance 714:722 potential pharmacogenetic relevance 688:722 potential pharmacogenetic relevance 688:722 We discovered a rare single nucleotide UGT2B7 variant of potential pharmacogenetic relevance that encodes a nonconservative amino acid substitution at codon 121. 27612916 6 36 theme inhibition 1151:1160 arg1 treatment 1113:1121 endoglycosidase H treatment 1095:1121 endoglycosidase H treatment of microsomal fractions and inhibition of N-glycosylation of endogenously produced UGT2B7 with tunicamycin in human embryonic kidney (HEK293) cells 1095:1269 This amino acid change was predicted to create a putative N-glycosylation motif NX(S/T) subsequently validated upon endoglycosidase H treatment of microsomal fractions and inhibition of N-glycosylation of endogenously produced UGT2B7 with tunicamycin in human embryonic kidney (HEK293) cells. 27612916 0 37 theme UGT2B7 7:12 arg1 Variant 14:20 A Rare UGT2B7 Variant 0:20 A Rare UGT2B7 Variant 0:20 A Rare UGT2B7 Variant Creates a Novel N-Glycosylation Site at Codon 121 with Impaired Enzyme Activity. 27612916 7 38 theme mycophenolic 1466:1477 arg1 acid 1479:1482 mycophenolic acid 1466:1482 mycophenolic acid 1466:1482 The presence of an additional N-linked glycan on the UGT2B7 enzyme, likely affecting proper protein folding, resulted in a significant decrease of 49% and 40% in the formation of zidovudine and mycophenolic acid glucuronides, respectively. 27612916 3 39 theme common 399:404 arg1 variants 406:413 common variants 399:413 common variants 399:413 Most studies currently survey common variants and examine only a small fraction of the genetic diversity; however, rare variants (frequency <1%) might have a significant effect because they are predicted to greatly outnumber common variants in the human genome. 27612916 9 40 from consequences 1907:1918 arg1 metabolism 1928:1937 drug metabolism 1923:1937 drug metabolism 1923:1937 Collectively, these variants have the potential to increase the proportion of variance explained in the UGT pathway resulting from changes in PTMs, such as N-linked glycosylation with consequences on drug metabolism. 27612916 3 41 theme small 434:438 arg1 fraction 440:447 only a small fraction 427:447 only a small fraction of the genetic diversity 427:472 Most studies currently survey common variants and examine only a small fraction of the genetic diversity; however, rare variants (frequency <1%) might have a significant effect because they are predicted to greatly outnumber common variants in the human genome. 27612916 6 42 from cells 1265:1269 arg1 N-glycosylation 1165:1179 N-glycosylation 1165:1179 N-glycosylation of endogenously produced UGT2B7 with tunicamycin in human embryonic kidney (HEK293) cells 1165:1269 This amino acid change was predicted to create a putative N-glycosylation motif NX(S/T) subsequently validated upon endoglycosidase H treatment of microsomal fractions and inhibition of N-glycosylation of endogenously produced UGT2B7 with tunicamycin in human embryonic kidney (HEK293) cells. 27612916 7 43 theme zidovudine 1451:1460 arg1 formation 1438:1446 the formation 1434:1446 the formation of zidovudine and mycophenolic acid glucuronides 1434:1495 The presence of an additional N-linked glycan on the UGT2B7 enzyme, likely affecting proper protein folding, resulted in a significant decrease of 49% and 40% in the formation of zidovudine and mycophenolic acid glucuronides, respectively. 27612916 6 44 theme amino 984:988 arg1 change 995:1000 This amino acid change 979:1000 This amino acid change 979:1000 This amino acid change was predicted to create a putative N-glycosylation motif NX(S/T) subsequently validated upon endoglycosidase H treatment of microsomal fractions and inhibition of N-glycosylation of endogenously produced UGT2B7 with tunicamycin in human embryonic kidney (HEK293) cells. 27612916 0 45 theme Novel 32:36 arg1 Site 54:57 a Novel N-Glycosylation Site 30:57 a Novel N-Glycosylation Site at Codon 121 with Impaired Enzyme Activity 30:100 A Rare UGT2B7 Variant Creates a Novel N-Glycosylation Site at Codon 121 with Impaired Enzyme Activity. 27612916 3 46 theme genetic 456:462 arg1 diversity 464:472 the genetic diversity 452:472 the genetic diversity 452:472 Most studies currently survey common variants and examine only a small fraction of the genetic diversity; however, rare variants (frequency <1%) might have a significant effect because they are predicted to greatly outnumber common variants in the human genome. 27612916 7 47 dep zidovudine 1451:1460 arg1 glucuronides 1484:1495 glucuronides 1484:1495 glucuronides 1484:1495 The presence of an additional N-linked glycan on the UGT2B7 enzyme, likely affecting proper protein folding, resulted in a significant decrease of 49% and 40% in the formation of zidovudine and mycophenolic acid glucuronides, respectively. 27612916 7 48 from presence 1276:1283 arg1 enzyme 1332:1337 the UGT2B7 enzyme 1321:1337 the UGT2B7 enzyme 1321:1337 The presence of an additional N-linked glycan on the UGT2B7 enzyme, likely affecting proper protein folding, resulted in a significant decrease of 49% and 40% in the formation of zidovudine and mycophenolic acid glucuronides, respectively. 27612916 8 49 theme Genetic 1545:1551 arg1 Variations 1553:1562 Short Genetic Variations 1539:1562 the Short Genetic Variations database 1535:1571 A systematic survey of the Short Genetic Variations database uncovered 32 rare, naturally occurring missense variations predicted to create or disrupt N-glycosylation sequence motifs in the other UGT2B enzymes. 27612916 1 50 gly glycoproteins 163:175 arg1 glycoproteins 163:175 glycoproteins 163:175 glycoproteins that reside in the endoplasmic reticulum membranes and that undergo post-translational modifications (PTMs) 163:283 The UDP glucuronosyltransferase (UGT) superfamily comprises glycoproteins that reside in the endoplasmic reticulum membranes and that undergo post-translational modifications (PTMs). 27612916 2 51 theme wide 346:349 arg1 drugs 362:366 drugs 362:366 drugs 362:366 UGT2B7 is of particular interest because of its action on a wide variety of drugs. 27612916 2 51 theme wide 346:349 arg1 variety 351:357 a wide variety 344:357 a wide variety of drugs 344:366 UGT2B7 is of particular interest because of its action on a wide variety of drugs. 27612916 1 52 theme post-translational 245:262 arg1 modifications 264:276 post-translational modifications 245:276 post-translational modifications (PTMs) 245:283 The UDP glucuronosyltransferase (UGT) superfamily comprises glycoproteins that reside in the endoplasmic reticulum membranes and that undergo post-translational modifications (PTMs). 27612916 1 52 theme post-translational 245:262 arg1 PTMs 279:282 PTMs 279:282 PTMs 279:282 The UDP glucuronosyltransferase (UGT) superfamily comprises glycoproteins that reside in the endoplasmic reticulum membranes and that undergo post-translational modifications (PTMs). 27612916 7 53 theme % 1421:1421 arg1 decrease 1407:1414 a significant decrease 1393:1414 a significant decrease of 49% and 40% in the formation of zidovudine and mycophenolic acid glucuronides, respectively 1393:1509 The presence of an additional N-linked glycan on the UGT2B7 enzyme, likely affecting proper protein folding, resulted in a significant decrease of 49% and 40% in the formation of zidovudine and mycophenolic acid glucuronides, respectively. 27612916 6 54 theme putative 1028:1035 arg1 motif 1053:1057 a putative N-glycosylation motif NX(S/T) 1026:1065 a putative N-glycosylation motif NX(S/T) subsequently validated upon endoglycosidase H treatment of microsomal fractions and inhibition of N-glycosylation of endogenously produced UGT2B7 with tunicamycin in human embryonic kidney (HEK293) cells 1026:1269 This amino acid change was predicted to create a putative N-glycosylation motif NX(S/T) subsequently validated upon endoglycosidase H treatment of microsomal fractions and inhibition of N-glycosylation of endogenously produced UGT2B7 with tunicamycin in human embryonic kidney (HEK293) cells. 27612916 8 55 theme database 1564:1571 arg1 survey 1525:1530 A systematic survey 1512:1530 A systematic survey of the Short Genetic Variations database 1512:1571 A systematic survey of the Short Genetic Variations database uncovered 32 rare, naturally occurring missense variations predicted to create or disrupt N-glycosylation sequence motifs in the other UGT2B enzymes. 27612916 6 56 theme kidney 1249:1254 arg1 cells 1265:1269 human embryonic kidney (HEK293) cells 1233:1269 human embryonic kidney (HEK293) cells 1233:1269 This amino acid change was predicted to create a putative N-glycosylation motif NX(S/T) subsequently validated upon endoglycosidase H treatment of microsomal fractions and inhibition of N-glycosylation of endogenously produced UGT2B7 with tunicamycin in human embryonic kidney (HEK293) cells. 27612916 6 57 theme H 1111:1111 arg1 treatment 1113:1121 endoglycosidase H treatment 1095:1121 endoglycosidase H treatment of microsomal fractions and inhibition of N-glycosylation of endogenously produced UGT2B7 with tunicamycin in human embryonic kidney (HEK293) cells 1095:1269 This amino acid change was predicted to create a putative N-glycosylation motif NX(S/T) subsequently validated upon endoglycosidase H treatment of microsomal fractions and inhibition of N-glycosylation of endogenously produced UGT2B7 with tunicamycin in human embryonic kidney (HEK293) cells. 27612916 6 58 theme microsomal 1126:1135 arg1 fractions 1137:1145 microsomal fractions 1126:1145 microsomal fractions 1126:1145 This amino acid change was predicted to create a putative N-glycosylation motif NX(S/T) subsequently validated upon endoglycosidase H treatment of microsomal fractions and inhibition of N-glycosylation of endogenously produced UGT2B7 with tunicamycin in human embryonic kidney (HEK293) cells. 27612916 6 59 theme human 1233:1237 arg1 kidney 1249:1254 human embryonic kidney 1233:1254 human embryonic kidney (HEK293) cells 1233:1269 This amino acid change was predicted to create a putative N-glycosylation motif NX(S/T) subsequently validated upon endoglycosidase H treatment of microsomal fractions and inhibition of N-glycosylation of endogenously produced UGT2B7 with tunicamycin in human embryonic kidney (HEK293) cells. 27612916 6 59 theme human 1233:1237 arg1 HEK293 1257:1262 HEK293 1257:1262 HEK293 1257:1262 This amino acid change was predicted to create a putative N-glycosylation motif NX(S/T) subsequently validated upon endoglycosidase H treatment of microsomal fractions and inhibition of N-glycosylation of endogenously produced UGT2B7 with tunicamycin in human embryonic kidney (HEK293) cells. 27612916 0 60 with Site 54:57 arg1 Activity 93:100 Impaired Enzyme Activity 77:100 Impaired Enzyme Activity 77:100 A Rare UGT2B7 Variant Creates a Novel N-Glycosylation Site at Codon 121 with Impaired Enzyme Activity. 27612916 3 61 theme frequency 499:507 arg1 % 511:511 frequency <1% 499:511 frequency <1% 499:511 Most studies currently survey common variants and examine only a small fraction of the genetic diversity; however, rare variants (frequency <1%) might have a significant effect because they are predicted to greatly outnumber common variants in the human genome. 27612916 3 61 theme frequency 499:507 arg1 variants 489:496 rare variants 484:496 rare variants (frequency <1%) 484:512 Most studies currently survey common variants and examine only a small fraction of the genetic diversity; however, rare variants (frequency <1%) might have a significant effect because they are predicted to greatly outnumber common variants in the human genome. 27612916 7 62 theme significant 1395:1405 arg1 decrease 1407:1414 a significant decrease 1393:1414 a significant decrease of 49% and 40% in the formation of zidovudine and mycophenolic acid glucuronides, respectively 1393:1509 The presence of an additional N-linked glycan on the UGT2B7 enzyme, likely affecting proper protein folding, resulted in a significant decrease of 49% and 40% in the formation of zidovudine and mycophenolic acid glucuronides, respectively. 27612916 9 63 contain have 1752:1755 arg1 variants 1743:1750 these variants 1737:1750 these variants 1737:1750 Collectively, these variants have the potential to increase the proportion of variance explained in the UGT pathway resulting from changes in PTMs, such as N-linked glycosylation with consequences on drug metabolism. 27612916 9 63 contain have 1752:1755 arg2 potential 1761:1769 the potential to increase the proportion of variance explained in the UGT pathway resulting from changes in PTMs, such as N-linked glycosylation with consequences on drug metabolism 1757:1937 the potential to increase the proportion of variance explained in the UGT pathway resulting from changes in PTMs, such as N-linked glycosylation with consequences on drug metabolism 1757:1937 Collectively, these variants have the potential to increase the proportion of variance explained in the UGT pathway resulting from changes in PTMs, such as N-linked glycosylation with consequences on drug metabolism. 27612916 8 64 theme N-glycosylation 1663:1677 arg1 motifs 1688:1693 N-glycosylation sequence motifs 1663:1693 N-glycosylation sequence motifs in the other UGT2B enzymes 1663:1720 A systematic survey of the Short Genetic Variations database uncovered 32 rare, naturally occurring missense variations predicted to create or disrupt N-glycosylation sequence motifs in the other UGT2B enzymes. 27612916 7 65 from decrease 1407:1414 arg1 formation 1438:1446 the formation 1434:1446 the formation of zidovudine and mycophenolic acid glucuronides 1434:1495 The presence of an additional N-linked glycan on the UGT2B7 enzyme, likely affecting proper protein folding, resulted in a significant decrease of 49% and 40% in the formation of zidovudine and mycophenolic acid glucuronides, respectively. 27612916 6 66 theme endoglycosidase 1095:1109 arg1 H 1111:1111 endoglycosidase H 1095:1111 endoglycosidase H treatment of microsomal fractions and inhibition of N-glycosylation of endogenously produced UGT2B7 with tunicamycin in human embryonic kidney (HEK293) cells 1095:1269 This amino acid change was predicted to create a putative N-glycosylation motif NX(S/T) subsequently validated upon endoglycosidase H treatment of microsomal fractions and inhibition of N-glycosylation of endogenously produced UGT2B7 with tunicamycin in human embryonic kidney (HEK293) cells. 27612916 2 67 theme particular 299:308 arg1 interest 310:317 particular interest 299:317 particular interest 299:317 UGT2B7 is of particular interest because of its action on a wide variety of drugs. 27612916 7 68 theme proper 1357:1362 arg1 folding 1372:1378 proper protein folding 1357:1378 proper protein folding 1357:1378 The presence of an additional N-linked glycan on the UGT2B7 enzyme, likely affecting proper protein folding, resulted in a significant decrease of 49% and 40% in the formation of zidovudine and mycophenolic acid glucuronides, respectively. 27612916 1 69 theme endoplasmic 196:206 arg1 reticulum 208:216 the endoplasmic reticulum 192:216 the endoplasmic reticulum membranes 192:226 The UDP glucuronosyltransferase (UGT) superfamily comprises glycoproteins that reside in the endoplasmic reticulum membranes and that undergo post-translational modifications (PTMs). 27612916 6 70 theme produced 1197:1204 arg1 UGT2B7 1206:1211 endogenously produced UGT2B7 1184:1211 endogenously produced UGT2B7 with tunicamycin in human embryonic kidney (HEK293) cells 1184:1269 This amino acid change was predicted to create a putative N-glycosylation motif NX(S/T) subsequently validated upon endoglycosidase H treatment of microsomal fractions and inhibition of N-glycosylation of endogenously produced UGT2B7 with tunicamycin in human embryonic kidney (HEK293) cells. 27612916 8 71 theme UGT2B 1708:1712 arg1 enzymes 1714:1720 the other UGT2B enzymes 1698:1720 the other UGT2B enzymes 1698:1720 A systematic survey of the Short Genetic Variations database uncovered 32 rare, naturally occurring missense variations predicted to create or disrupt N-glycosylation sequence motifs in the other UGT2B enzymes. 27612916 5 72 theme volunteers 879:888 arg1 population 853:862 a population 851:862 a population of 305 healthy volunteers 851:888 This low-frequency variation, found in two individuals of a population of 305 healthy volunteers, leads to the translation of an asparagine instead of an aspartic acid (UGT2B7 p.D121N). 27612916 7 73 from % 1429:1429 arg1 formation 1438:1446 the formation 1434:1446 the formation of zidovudine and mycophenolic acid glucuronides 1434:1495 The presence of an additional N-linked glycan on the UGT2B7 enzyme, likely affecting proper protein folding, resulted in a significant decrease of 49% and 40% in the formation of zidovudine and mycophenolic acid glucuronides, respectively. 27612916 9 74 theme drug 1923:1926 arg1 metabolism 1928:1937 drug metabolism 1923:1937 drug metabolism 1923:1937 Collectively, these variants have the potential to increase the proportion of variance explained in the UGT pathway resulting from changes in PTMs, such as N-linked glycosylation with consequences on drug metabolism. 27612916 4 75 theme nucleotide 659:668 arg1 variant 677:683 a rare single nucleotide UGT2B7 variant 645:683 a rare single nucleotide UGT2B7 variant of potential pharmacogenetic relevance that encodes a nonconservative amino acid substitution at codon 121 645:790 We discovered a rare single nucleotide UGT2B7 variant of potential pharmacogenetic relevance that encodes a nonconservative amino acid substitution at codon 121. 27612916 4 75 theme nucleotide 659:668 arg1 substitution 766:777 a nonconservative amino acid substitution 737:777 a nonconservative amino acid substitution at codon 121 737:790 We discovered a rare single nucleotide UGT2B7 variant of potential pharmacogenetic relevance that encodes a nonconservative amino acid substitution at codon 121. 27612916 1 76 theme UDP 107:109 arg1 UGT 136:138 UGT 136:138 UGT 136:138 The UDP glucuronosyltransferase (UGT) superfamily comprises glycoproteins that reside in the endoplasmic reticulum membranes and that undergo post-translational modifications (PTMs). 27612916 1 76 theme UDP 107:109 arg1 glucuronosyltransferase 111:133 UDP glucuronosyltransferase 107:133 The UDP glucuronosyltransferase (UGT) superfamily 103:151 The UDP glucuronosyltransferase (UGT) superfamily comprises glycoproteins that reside in the endoplasmic reticulum membranes and that undergo post-translational modifications (PTMs). 27612916 6 77 from UGT2B7 1206:1211 arg1 cells 1265:1269 human embryonic kidney (HEK293) cells 1233:1269 human embryonic kidney (HEK293) cells 1233:1269 This amino acid change was predicted to create a putative N-glycosylation motif NX(S/T) subsequently validated upon endoglycosidase H treatment of microsomal fractions and inhibition of N-glycosylation of endogenously produced UGT2B7 with tunicamycin in human embryonic kidney (HEK293) cells. 27612916 5 78 located found 823:827 arg1 individuals 836:846 two individuals 832:846 two individuals of a population of 305 healthy volunteers 832:888 This low-frequency variation, found in two individuals of a population of 305 healthy volunteers, leads to the translation of an asparagine instead of an aspartic acid (UGT2B7 p.D121N). 27612916 5 78 located found 823:827 arg2 variation 812:820 This low-frequency variation 793:820 This low-frequency variation 793:820 This low-frequency variation, found in two individuals of a population of 305 healthy volunteers, leads to the translation of an asparagine instead of an aspartic acid (UGT2B7 p.D121N). 27612916 5 79 theme population 853:862 arg1 individuals 836:846 two individuals 832:846 two individuals of a population of 305 healthy volunteers 832:888 This low-frequency variation, found in two individuals of a population of 305 healthy volunteers, leads to the translation of an asparagine instead of an aspartic acid (UGT2B7 p.D121N). 27612916 6 80 with UGT2B7 1206:1211 arg1 tunicamycin 1218:1228 tunicamycin 1218:1228 tunicamycin 1218:1228 This amino acid change was predicted to create a putative N-glycosylation motif NX(S/T) subsequently validated upon endoglycosidase H treatment of microsomal fractions and inhibition of N-glycosylation of endogenously produced UGT2B7 with tunicamycin in human embryonic kidney (HEK293) cells. 27612916 7 81 theme glycan 1311:1316 arg1 presence 1276:1283 The presence 1272:1283 The presence 1272:1283 The presence of an additional N-linked glycan on the UGT2B7 enzyme, likely affecting proper protein folding, resulted in a significant decrease of 49% and 40% in the formation of zidovudine and mycophenolic acid glucuronides, respectively. 27612916 4 82 theme rare 647:650 arg1 variant 677:683 a rare single nucleotide UGT2B7 variant 645:683 a rare single nucleotide UGT2B7 variant of potential pharmacogenetic relevance that encodes a nonconservative amino acid substitution at codon 121 645:790 We discovered a rare single nucleotide UGT2B7 variant of potential pharmacogenetic relevance that encodes a nonconservative amino acid substitution at codon 121. 27612916 4 82 theme rare 647:650 arg1 substitution 766:777 a nonconservative amino acid substitution 737:777 a nonconservative amino acid substitution at codon 121 737:790 We discovered a rare single nucleotide UGT2B7 variant of potential pharmacogenetic relevance that encodes a nonconservative amino acid substitution at codon 121. 27612916 6 83 from N-glycosylation 1165:1179 arg1 cells 1265:1269 human embryonic kidney (HEK293) cells 1233:1269 human embryonic kidney (HEK293) cells 1233:1269 This amino acid change was predicted to create a putative N-glycosylation motif NX(S/T) subsequently validated upon endoglycosidase H treatment of microsomal fractions and inhibition of N-glycosylation of endogenously produced UGT2B7 with tunicamycin in human embryonic kidney (HEK293) cells. 27612916 0 84 theme Impaired 77:84 arg1 Activity 93:100 Impaired Enzyme Activity 77:100 Impaired Enzyme Activity 77:100 A Rare UGT2B7 Variant Creates a Novel N-Glycosylation Site at Codon 121 with Impaired Enzyme Activity. 27612916 5 85 theme asparagine 922:931 arg1 translation 904:914 the translation 900:914 the translation of an asparagine 900:931 This low-frequency variation, found in two individuals of a population of 305 healthy volunteers, leads to the translation of an asparagine instead of an aspartic acid (UGT2B7 p.D121N). 27612916 6 86 gly N-glycosylation 1037:1051 arg2 motif 1053:1057 a putative N-glycosylation motif NX(S/T) 1026:1065 a putative N-glycosylation motif NX(S/T) subsequently validated upon endoglycosidase H treatment of microsomal fractions and inhibition of N-glycosylation of endogenously produced UGT2B7 with tunicamycin in human embryonic kidney (HEK293) cells 1026:1269 This amino acid change was predicted to create a putative N-glycosylation motif NX(S/T) subsequently validated upon endoglycosidase H treatment of microsomal fractions and inhibition of N-glycosylation of endogenously produced UGT2B7 with tunicamycin in human embryonic kidney (HEK293) cells. 27612916 7 87 from glycan 1311:1316 arg1 enzyme 1332:1337 the UGT2B7 enzyme 1321:1337 the UGT2B7 enzyme 1321:1337 The presence of an additional N-linked glycan on the UGT2B7 enzyme, likely affecting proper protein folding, resulted in a significant decrease of 49% and 40% in the formation of zidovudine and mycophenolic acid glucuronides, respectively. 27612916 4 88 theme nonconservative 739:753 arg1 variant 677:683 a rare single nucleotide UGT2B7 variant 645:683 a rare single nucleotide UGT2B7 variant of potential pharmacogenetic relevance that encodes a nonconservative amino acid substitution at codon 121 645:790 We discovered a rare single nucleotide UGT2B7 variant of potential pharmacogenetic relevance that encodes a nonconservative amino acid substitution at codon 121. 27612916 4 88 theme nonconservative 739:753 arg1 substitution 766:777 a nonconservative amino acid substitution 737:777 a nonconservative amino acid substitution at codon 121 737:790 We discovered a rare single nucleotide UGT2B7 variant of potential pharmacogenetic relevance that encodes a nonconservative amino acid substitution at codon 121. 27612916 0 89 theme Rare 2:5 arg1 Variant 14:20 A Rare UGT2B7 Variant 0:20 A Rare UGT2B7 Variant 0:20 A Rare UGT2B7 Variant Creates a Novel N-Glycosylation Site at Codon 121 with Impaired Enzyme Activity. 27612916 3 90 contain have 520:523 arg1 % 511:511 frequency <1% 499:511 frequency <1% 499:511 Most studies currently survey common variants and examine only a small fraction of the genetic diversity; however, rare variants (frequency <1%) might have a significant effect because they are predicted to greatly outnumber common variants in the human genome. 27612916 3 90 contain have 520:523 arg2 effect 539:544 a significant effect 525:544 a significant effect 525:544 Most studies currently survey common variants and examine only a small fraction of the genetic diversity; however, rare variants (frequency <1%) might have a significant effect because they are predicted to greatly outnumber common variants in the human genome. 27612916 3 90 contain have 520:523 arg1 variants 489:496 rare variants 484:496 rare variants (frequency <1%) 484:512 Most studies currently survey common variants and examine only a small fraction of the genetic diversity; however, rare variants (frequency <1%) might have a significant effect because they are predicted to greatly outnumber common variants in the human genome. 27612916 4 91 theme potential 688:696 arg1 relevance 714:722 potential pharmacogenetic relevance 688:722 potential pharmacogenetic relevance 688:722 We discovered a rare single nucleotide UGT2B7 variant of potential pharmacogenetic relevance that encodes a nonconservative amino acid substitution at codon 121. 27612916 2 92 theme drugs 362:366 arg1 drugs 362:366 drugs 362:366 drugs 362:366 UGT2B7 is of particular interest because of its action on a wide variety of drugs. 27612916 2 92 theme drugs 362:366 arg1 variety 351:357 a wide variety 344:357 a wide variety of drugs 344:366 UGT2B7 is of particular interest because of its action on a wide variety of drugs. 27612916 7 93 from enzyme 1332:1337 arg1 presence 1276:1283 The presence 1272:1283 The presence 1272:1283 The presence of an additional N-linked glycan on the UGT2B7 enzyme, likely affecting proper protein folding, resulted in a significant decrease of 49% and 40% in the formation of zidovudine and mycophenolic acid glucuronides, respectively. 27612916 9 94 with glycosylation 1888:1900 arg1 consequences 1907:1918 consequences 1907:1918 consequences on drug metabolism 1907:1937 Collectively, these variants have the potential to increase the proportion of variance explained in the UGT pathway resulting from changes in PTMs, such as N-linked glycosylation with consequences on drug metabolism. 27612916 4 95 theme relevance 714:722 arg1 variant 677:683 a rare single nucleotide UGT2B7 variant 645:683 a rare single nucleotide UGT2B7 variant of potential pharmacogenetic relevance that encodes a nonconservative amino acid substitution at codon 121 645:790 We discovered a rare single nucleotide UGT2B7 variant of potential pharmacogenetic relevance that encodes a nonconservative amino acid substitution at codon 121. 27612916 4 95 theme relevance 714:722 arg1 substitution 766:777 a nonconservative amino acid substitution 737:777 a nonconservative amino acid substitution at codon 121 737:790 We discovered a rare single nucleotide UGT2B7 variant of potential pharmacogenetic relevance that encodes a nonconservative amino acid substitution at codon 121. 27612916 7 96 theme acid 1479:1482 arg1 formation 1438:1446 the formation 1434:1446 the formation of zidovudine and mycophenolic acid glucuronides 1434:1495 The presence of an additional N-linked glycan on the UGT2B7 enzyme, likely affecting proper protein folding, resulted in a significant decrease of 49% and 40% in the formation of zidovudine and mycophenolic acid glucuronides, respectively. 27612916 6 97 theme acid 990:993 arg1 change 995:1000 This amino acid change 979:1000 This amino acid change 979:1000 This amino acid change was predicted to create a putative N-glycosylation motif NX(S/T) subsequently validated upon endoglycosidase H treatment of microsomal fractions and inhibition of N-glycosylation of endogenously produced UGT2B7 with tunicamycin in human embryonic kidney (HEK293) cells. 27612916 8 98 theme systematic 1514:1523 arg1 survey 1525:1530 A systematic survey 1512:1530 A systematic survey of the Short Genetic Variations database 1512:1571 A systematic survey of the Short Genetic Variations database uncovered 32 rare, naturally occurring missense variations predicted to create or disrupt N-glycosylation sequence motifs in the other UGT2B enzymes. 27612916 3 99 theme common 594:599 arg1 variants 601:608 common variants 594:608 common variants in the human genome 594:628 Most studies currently survey common variants and examine only a small fraction of the genetic diversity; however, rare variants (frequency <1%) might have a significant effect because they are predicted to greatly outnumber common variants in the human genome. 27612916 0 100 theme N-Glycosylation 38:52 arg1 Site 54:57 a Novel N-Glycosylation Site 30:57 a Novel N-Glycosylation Site at Codon 121 with Impaired Enzyme Activity 30:100 A Rare UGT2B7 Variant Creates a Novel N-Glycosylation Site at Codon 121 with Impaired Enzyme Activity. 27612916 9 101 theme variance 1801:1808 arg1 proportion 1787:1796 the proportion 1783:1796 the proportion of variance explained in the UGT pathway resulting from changes in PTMs, such as N-linked glycosylation with consequences on drug metabolism 1783:1937 Collectively, these variants have the potential to increase the proportion of variance explained in the UGT pathway resulting from changes in PTMs, such as N-linked glycosylation with consequences on drug metabolism. 27612916 6 102 dep motif 1053:1057 arg1 S/T 1062:1064 S/T 1062:1064 S/T 1062:1064 This amino acid change was predicted to create a putative N-glycosylation motif NX(S/T) subsequently validated upon endoglycosidase H treatment of microsomal fractions and inhibition of N-glycosylation of endogenously produced UGT2B7 with tunicamycin in human embryonic kidney (HEK293) cells. 27612916 6 102 dep motif 1053:1057 arg1 NX 1059:1060 NX 1059:1060 a putative N-glycosylation motif NX(S/T) subsequently validated upon endoglycosidase H treatment of microsomal fractions and inhibition of N-glycosylation of endogenously produced UGT2B7 with tunicamycin in human embryonic kidney (HEK293) cells 1026:1269 This amino acid change was predicted to create a putative N-glycosylation motif NX(S/T) subsequently validated upon endoglycosidase H treatment of microsomal fractions and inhibition of N-glycosylation of endogenously produced UGT2B7 with tunicamycin in human embryonic kidney (HEK293) cells. 27612916 5 103 theme aspartic 947:954 arg1 acid 956:959 an aspartic acid 944:959 an aspartic acid (UGT2B7 p.D121N) 944:976 This low-frequency variation, found in two individuals of a population of 305 healthy volunteers, leads to the translation of an asparagine instead of an aspartic acid (UGT2B7 p.D121N). 27612916 5 103 theme aspartic 947:954 arg1 p.D121N 969:975 UGT2B7 p.D121N 962:975 UGT2B7 p.D121N 962:975 This low-frequency variation, found in two individuals of a population of 305 healthy volunteers, leads to the translation of an asparagine instead of an aspartic acid (UGT2B7 p.D121N). 27612916 8 104 theme Short 1539:1543 arg1 Variations 1553:1562 Short Genetic Variations 1539:1562 the Short Genetic Variations database 1535:1571 A systematic survey of the Short Genetic Variations database uncovered 32 rare, naturally occurring missense variations predicted to create or disrupt N-glycosylation sequence motifs in the other UGT2B enzymes. 27612916 3 105 theme human 617:621 arg1 genome 623:628 the human genome 613:628 the human genome 613:628 Most studies currently survey common variants and examine only a small fraction of the genetic diversity; however, rare variants (frequency <1%) might have a significant effect because they are predicted to greatly outnumber common variants in the human genome. 27612916 4 106 theme acid 761:764 arg1 variant 677:683 a rare single nucleotide UGT2B7 variant 645:683 a rare single nucleotide UGT2B7 variant of potential pharmacogenetic relevance that encodes a nonconservative amino acid substitution at codon 121 645:790 We discovered a rare single nucleotide UGT2B7 variant of potential pharmacogenetic relevance that encodes a nonconservative amino acid substitution at codon 121. 27612916 4 106 theme acid 761:764 arg1 substitution 766:777 a nonconservative amino acid substitution 737:777 a nonconservative amino acid substitution at codon 121 737:790 We discovered a rare single nucleotide UGT2B7 variant of potential pharmacogenetic relevance that encodes a nonconservative amino acid substitution at codon 121. 27612916 3 107 theme diversity 464:472 arg1 fraction 440:447 only a small fraction 427:447 only a small fraction of the genetic diversity 427:472 Most studies currently survey common variants and examine only a small fraction of the genetic diversity; however, rare variants (frequency <1%) might have a significant effect because they are predicted to greatly outnumber common variants in the human genome. 27612916 8 108 theme missense 1612:1619 arg1 variations 1621:1630 32 rare, naturally occurring missense variations 1583:1630 32 rare, naturally occurring missense variations predicted to create or disrupt N-glycosylation sequence motifs in the other UGT2B enzymes 1583:1720 A systematic survey of the Short Genetic Variations database uncovered 32 rare, naturally occurring missense variations predicted to create or disrupt N-glycosylation sequence motifs in the other UGT2B enzymes. 27612916 9 109 theme UGT 1827:1829 arg1 pathway 1831:1837 the UGT pathway 1823:1837 the UGT pathway resulting from changes in PTMs, such as N-linked glycosylation with consequences on drug metabolism 1823:1937 Collectively, these variants have the potential to increase the proportion of variance explained in the UGT pathway resulting from changes in PTMs, such as N-linked glycosylation with consequences on drug metabolism. 27612916 8 110 theme Variations 1553:1562 arg1 database 1564:1571 the Short Genetic Variations database 1535:1571 the Short Genetic Variations database 1535:1571 A systematic survey of the Short Genetic Variations database uncovered 32 rare, naturally occurring missense variations predicted to create or disrupt N-glycosylation sequence motifs in the other UGT2B enzymes. 27612916 6 111 gly N-glycosylation 1165:1179 arg1 UGT2B7 1206:1211 endogenously produced UGT2B7 1184:1211 endogenously produced UGT2B7 with tunicamycin in human embryonic kidney (HEK293) cells 1184:1269 This amino acid change was predicted to create a putative N-glycosylation motif NX(S/T) subsequently validated upon endoglycosidase H treatment of microsomal fractions and inhibition of N-glycosylation of endogenously produced UGT2B7 with tunicamycin in human embryonic kidney (HEK293) cells. 27612916 8 112 from motifs 1688:1693 arg1 enzymes 1714:1720 the other UGT2B enzymes 1698:1720 the other UGT2B enzymes 1698:1720 A systematic survey of the Short Genetic Variations database uncovered 32 rare, naturally occurring missense variations predicted to create or disrupt N-glycosylation sequence motifs in the other UGT2B enzymes. 27612916 3 113 theme Most 369:372 arg1 studies 374:380 Most studies 369:380 Most studies 369:380 Most studies currently survey common variants and examine only a small fraction of the genetic diversity; however, rare variants (frequency <1%) might have a significant effect because they are predicted to greatly outnumber common variants in the human genome. 26018173 9 0 link O-linked 1721:1728 arg1 profile 1744:1750 the full O-linked glycosylation profile 1712:1750 the full O-linked glycosylation profile of membrane-associated Env 1712:1777 Additionally, we report a newly observed O-linked glycosylation site, T606, and we show that the full O-linked glycosylation profile of membrane-associated Env is similar to that of soluble gp140. 26018173 9 0 link O-linked 1721:1728 arg1 similar 1782:1788 similar 1782:1788 similar 1782:1788 Additionally, we report a newly observed O-linked glycosylation site, T606, and we show that the full O-linked glycosylation profile of membrane-associated Env is similar to that of soluble gp140. 26018173 9 1 theme membrane-associated 1755:1773 arg1 Env 1775:1777 membrane-associated Env 1755:1777 membrane-associated Env 1755:1777 Additionally, we report a newly observed O-linked glycosylation site, T606, and we show that the full O-linked glycosylation profile of membrane-associated Env is similar to that of soluble gp140. 26018173 9 2 gly glycosylation 1669:1681 arg2 T606 1689:1692 T606 1689:1692 T606 1689:1692 Additionally, we report a newly observed O-linked glycosylation site, T606, and we show that the full O-linked glycosylation profile of membrane-associated Env is similar to that of soluble gp140. 26018173 9 2 gly glycosylation 1669:1681 arg2 site 1683:1686 a newly observed O-linked glycosylation site 1643:1686 a newly observed O-linked glycosylation site 1643:1686 Additionally, we report a newly observed O-linked glycosylation site, T606, and we show that the full O-linked glycosylation profile of membrane-associated Env is similar to that of soluble gp140. 26018173 13 3 theme membrane 2398:2405 arg1 glycoproteins 2416:2428 the HIV-1 membrane envelope glycoproteins 2388:2428 the HIV-1 membrane envelope glycoproteins 2388:2428 We found that the HIV-1 membrane envelope glycoproteins have a unique pattern of carbohydrates, with many high-mannose glycans and also, in some places, complex glycans. 26018173 2 4 theme Env 329:331 arg1 glycosylation 333:345 Extensive Env glycosylation 319:345 Extensive Env glycosylation 319:345 Extensive Env glycosylation provides HIV-1 with protection from the immune system, yet the glycans are also essential components of binding epitopes for numerous broadly neutralizing antibodies. 26018173 13 5 contain have 2430:2433 arg1 glycoproteins 2416:2428 the HIV-1 membrane envelope glycoproteins 2388:2428 the HIV-1 membrane envelope glycoproteins 2388:2428 We found that the HIV-1 membrane envelope glycoproteins have a unique pattern of carbohydrates, with many high-mannose glycans and also, in some places, complex glycans. 26018173 13 5 contain have 2430:2433 arg2 pattern 2444:2450 a unique pattern 2435:2450 a unique pattern of carbohydrates, with many high-mannose glycans 2435:2499 We found that the HIV-1 membrane envelope glycoproteins have a unique pattern of carbohydrates, with many high-mannose glycans and also, in some places, complex glycans. 26018173 14 6 from profile 2598:2604 arg1 different 2566:2574 different 2566:2574 different 2566:2574 This pattern was very different from the carbohydrate profile seen for a more easily produced soluble version of the envelope glycoprotein. 26018173 13 7 theme envelope 2407:2414 arg1 glycoproteins 2416:2428 the HIV-1 membrane envelope glycoproteins 2388:2428 the HIV-1 membrane envelope glycoproteins 2388:2428 We found that the HIV-1 membrane envelope glycoproteins have a unique pattern of carbohydrates, with many high-mannose glycans and also, in some places, complex glycans. 26018173 1 8 gly glycoprotein 184:195 arg1 glycoprotein 184:195 The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein 127:195 The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) 127:201 The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) trimer, which consists of the gp120 and gp41 subunits, is the focus of multiple strategies for vaccine development. 26018173 1 8 gly glycoprotein 184:195 arg1 focus 265:269 the focus 261:269 the focus of multiple strategies for vaccine development 261:316 The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) trimer, which consists of the gp120 and gp41 subunits, is the focus of multiple strategies for vaccine development. 26018173 1 8 gly glycoprotein 184:195 arg1 Env 198:200 Env 198:200 Env 198:200 The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) trimer, which consists of the gp120 and gp41 subunits, is the focus of multiple strategies for vaccine development. 26018173 9 9 gly glycosylation 1730:1742 arg1 Env 1775:1777 membrane-associated Env 1755:1777 membrane-associated Env 1755:1777 Additionally, we report a newly observed O-linked glycosylation site, T606, and we show that the full O-linked glycosylation profile of membrane-associated Env is similar to that of soluble gp140. 26018173 12 10 contain have 2195:2198 arg1 glycoproteins 2181:2193 The envelope glycoproteins 2168:2193 The envelope glycoproteins 2168:2193 The envelope glycoproteins have an extensive coat of carbohydrates (glycans), some of which are recognized by virus-neutralizing antibodies and some of which protect the virus from neutralizing antibodies. 26018173 12 10 contain have 2195:2198 arg2 coat 2213:2216 an extensive coat 2200:2216 an extensive coat of carbohydrates (glycans), some of which are recognized by virus-neutralizing antibodies and some of which protect the virus from neutralizing antibodies 2200:2371 The envelope glycoproteins have an extensive coat of carbohydrates (glycans), some of which are recognized by virus-neutralizing antibodies and some of which protect the virus from neutralizing antibodies. 26018173 1 11 theme envelope 175:182 arg1 glycoprotein 184:195 The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein 127:195 The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) 127:201 The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) trimer, which consists of the gp120 and gp41 subunits, is the focus of multiple strategies for vaccine development. 26018173 1 11 theme envelope 175:182 arg1 focus 265:269 the focus 261:269 the focus of multiple strategies for vaccine development 261:316 The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) trimer, which consists of the gp120 and gp41 subunits, is the focus of multiple strategies for vaccine development. 26018173 1 11 theme envelope 175:182 arg1 Env 198:200 Env 198:200 Env 198:200 The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) trimer, which consists of the gp120 and gp41 subunits, is the focus of multiple strategies for vaccine development. 26018173 7 12 theme soluble 1473:1479 arg1 gp120 1481:1485 soluble gp120 1473:1485 soluble gp120 1473:1485 While many of the sites contain exclusively high-mannose glycans, others retain complex glycans, resulting in a glycan profile that cannot currently be mimicked on soluble gp120 or gp140 preparations. 26018173 4 13 theme mammalian 826:834 arg1 cells 836:840 mammalian cells 826:840 mammalian cells 826:840 Here we show that exogenous membrane-anchored Envs, which can be produced in large quantities in mammalian cells, also display a virion-like glycan profile, where the glycoprotein is extensively decorated with high-mannose glycans. 26018173 15 14 theme carbohydrate 2806:2817 arg1 profile 2819:2825 a carbohydrate profile 2804:2825 a carbohydrate profile that would be desirable to mimic with a vaccine 2804:2873 Our results provide a detailed characterization of the glycans on the natural membrane envelope glycoproteins of HIV-1, a carbohydrate profile that would be desirable to mimic with a vaccine. 26018173 15 14 theme carbohydrate 2806:2817 arg1 desirable 2841:2849 desirable 2841:2849 desirable 2841:2849 Our results provide a detailed characterization of the glycans on the natural membrane envelope glycoproteins of HIV-1, a carbohydrate profile that would be desirable to mimic with a vaccine. 26018173 15 14 theme carbohydrate 2806:2817 arg1 glycoproteins 2780:2792 the natural membrane envelope glycoproteins 2750:2792 the natural membrane envelope glycoproteins of HIV-1 2750:2801 Our results provide a detailed characterization of the glycans on the natural membrane envelope glycoproteins of HIV-1, a carbohydrate profile that would be desirable to mimic with a vaccine. 26018173 13 15 theme HIV-1 2392:2396 arg1 glycoproteins 2416:2428 the HIV-1 membrane envelope glycoproteins 2388:2428 the HIV-1 membrane envelope glycoproteins 2388:2428 We found that the HIV-1 membrane envelope glycoproteins have a unique pattern of carbohydrates, with many high-mannose glycans and also, in some places, complex glycans. 26018173 9 16 link O-linked 1660:1667 arg1 T606 1689:1692 T606 1689:1692 T606 1689:1692 Additionally, we report a newly observed O-linked glycosylation site, T606, and we show that the full O-linked glycosylation profile of membrane-associated Env is similar to that of soluble gp140. 26018173 9 16 link O-linked 1660:1667 arg1 site 1683:1686 a newly observed O-linked glycosylation site 1643:1686 a newly observed O-linked glycosylation site 1643:1686 Additionally, we report a newly observed O-linked glycosylation site, T606, and we show that the full O-linked glycosylation profile of membrane-associated Env is similar to that of soluble gp140. 26018173 9 17 theme O-linked 1721:1728 arg1 profile 1744:1750 the full O-linked glycosylation profile 1712:1750 the full O-linked glycosylation profile of membrane-associated Env 1712:1777 Additionally, we report a newly observed O-linked glycosylation site, T606, and we show that the full O-linked glycosylation profile of membrane-associated Env is similar to that of soluble gp140. 26018173 9 17 theme O-linked 1721:1728 arg1 similar 1782:1788 similar 1782:1788 similar 1782:1788 Additionally, we report a newly observed O-linked glycosylation site, T606, and we show that the full O-linked glycosylation profile of membrane-associated Env is similar to that of soluble gp140. 26018173 11 18 theme human 2011:2015 arg1 type 2040:2043 human immunodeficiency virus type 1 2011:2045 human immunodeficiency virus type 1 (HIV-1) infection 2011:2063 IMPORTANCE: A vaccine that protects against human immunodeficiency virus type 1 (HIV-1) infection should elicit antibodies that bind to the surface envelope glycoproteins on the membrane of the virus. 26018173 11 18 theme human 2011:2015 arg1 HIV-1 2048:2052 HIV-1 2048:2052 HIV-1 2048:2052 IMPORTANCE: A vaccine that protects against human immunodeficiency virus type 1 (HIV-1) infection should elicit antibodies that bind to the surface envelope glycoproteins on the membrane of the virus. 26018173 3 19 theme discovery 709:717 arg1 research 719:726 vaccine discovery research 701:726 vaccine discovery research 701:726 Recent studies have shown that when Env is isolated from virions, its glycosylation profile differs significantly from that of soluble forms of Env (gp120 or gp140) predominantly used in vaccine discovery research. 26018173 13 20 theme complex 2527:2533 arg1 glycans 2535:2541 complex glycans 2527:2541 complex glycans 2527:2541 We found that the HIV-1 membrane envelope glycoproteins have a unique pattern of carbohydrates, with many high-mannose glycans and also, in some places, complex glycans. 26018173 5 21 theme glycopeptide 1057:1068 arg1 method 1049:1054 a high-fidelity profiling method 1023:1054 a high-fidelity profiling method 1023:1054 Additionally, because we characterized the glycosylation with a high-fidelity profiling method, glycopeptide analysis, an unprecedented level of molecular detail regarding membrane Env glycosylation and its heterogeneity is presented. 26018173 5 21 theme glycopeptide 1057:1068 arg1 analysis 1070:1077 glycopeptide analysis 1057:1077 glycopeptide analysis 1057:1077 Additionally, because we characterized the glycosylation with a high-fidelity profiling method, glycopeptide analysis, an unprecedented level of molecular detail regarding membrane Env glycosylation and its heterogeneity is presented. 26018173 14 22 theme glycoprotein 2670:2681 arg1 version 2646:2652 a more easily produced soluble version 2615:2652 a more easily produced soluble version of the envelope glycoprotein 2615:2681 This pattern was very different from the carbohydrate profile seen for a more easily produced soluble version of the envelope glycoprotein. 26018173 11 23 theme virus 2034:2038 arg1 type 2040:2043 human immunodeficiency virus type 1 2011:2045 human immunodeficiency virus type 1 (HIV-1) infection 2011:2063 IMPORTANCE: A vaccine that protects against human immunodeficiency virus type 1 (HIV-1) infection should elicit antibodies that bind to the surface envelope glycoproteins on the membrane of the virus. 26018173 11 23 theme virus 2034:2038 arg1 HIV-1 2048:2052 HIV-1 2048:2052 HIV-1 2048:2052 IMPORTANCE: A vaccine that protects against human immunodeficiency virus type 1 (HIV-1) infection should elicit antibodies that bind to the surface envelope glycoproteins on the membrane of the virus. 26018173 12 24 theme extensive 2203:2211 arg1 coat 2213:2216 an extensive coat 2200:2216 an extensive coat of carbohydrates (glycans), some of which are recognized by virus-neutralizing antibodies and some of which protect the virus from neutralizing antibodies 2200:2371 The envelope glycoproteins have an extensive coat of carbohydrates (glycans), some of which are recognized by virus-neutralizing antibodies and some of which protect the virus from neutralizing antibodies. 26018173 4 25 theme virion-like 858:868 arg1 profile 877:883 a virion-like glycan profile 856:883 a virion-like glycan profile 856:883 Here we show that exogenous membrane-anchored Envs, which can be produced in large quantities in mammalian cells, also display a virion-like glycan profile, where the glycoprotein is extensively decorated with high-mannose glycans. 26018173 15 26 from characterization 2715:2730 arg1 profile 2819:2825 a carbohydrate profile 2804:2825 a carbohydrate profile that would be desirable to mimic with a vaccine 2804:2873 Our results provide a detailed characterization of the glycans on the natural membrane envelope glycoproteins of HIV-1, a carbohydrate profile that would be desirable to mimic with a vaccine. 26018173 15 26 from characterization 2715:2730 arg1 desirable 2841:2849 desirable 2841:2849 desirable 2841:2849 Our results provide a detailed characterization of the glycans on the natural membrane envelope glycoproteins of HIV-1, a carbohydrate profile that would be desirable to mimic with a vaccine. 26018173 15 26 from characterization 2715:2730 arg1 glycoproteins 2780:2792 the natural membrane envelope glycoproteins 2750:2792 the natural membrane envelope glycoproteins of HIV-1 2750:2801 Our results provide a detailed characterization of the glycans on the natural membrane envelope glycoproteins of HIV-1, a carbohydrate profile that would be desirable to mimic with a vaccine. 26018173 5 27 theme high-fidelity 1025:1037 arg1 method 1049:1054 a high-fidelity profiling method 1023:1054 a high-fidelity profiling method 1023:1054 Additionally, because we characterized the glycosylation with a high-fidelity profiling method, glycopeptide analysis, an unprecedented level of molecular detail regarding membrane Env glycosylation and its heterogeneity is presented. 26018173 5 27 theme high-fidelity 1025:1037 arg1 analysis 1070:1077 glycopeptide analysis 1057:1077 glycopeptide analysis 1057:1077 Additionally, because we characterized the glycosylation with a high-fidelity profiling method, glycopeptide analysis, an unprecedented level of molecular detail regarding membrane Env glycosylation and its heterogeneity is presented. 26018173 5 28 theme profiling 1039:1047 arg1 method 1049:1054 a high-fidelity profiling method 1023:1054 a high-fidelity profiling method 1023:1054 Additionally, because we characterized the glycosylation with a high-fidelity profiling method, glycopeptide analysis, an unprecedented level of molecular detail regarding membrane Env glycosylation and its heterogeneity is presented. 26018173 5 28 theme profiling 1039:1047 arg1 analysis 1070:1077 glycopeptide analysis 1057:1077 glycopeptide analysis 1057:1077 Additionally, because we characterized the glycosylation with a high-fidelity profiling method, glycopeptide analysis, an unprecedented level of molecular detail regarding membrane Env glycosylation and its heterogeneity is presented. 26018173 1 29 theme human 131:135 arg1 glycoprotein 184:195 The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein 127:195 The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) 127:201 The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) trimer, which consists of the gp120 and gp41 subunits, is the focus of multiple strategies for vaccine development. 26018173 1 29 theme human 131:135 arg1 focus 265:269 the focus 261:269 the focus of multiple strategies for vaccine development 261:316 The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) trimer, which consists of the gp120 and gp41 subunits, is the focus of multiple strategies for vaccine development. 26018173 1 29 theme human 131:135 arg1 Env 198:200 Env 198:200 Env 198:200 The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) trimer, which consists of the gp120 and gp41 subunits, is the focus of multiple strategies for vaccine development. 26018173 4 30 gly glycoprotein 896:907 arg1 glycoprotein 896:907 the glycoprotein 892:907 the glycoprotein 892:907 Here we show that exogenous membrane-anchored Envs, which can be produced in large quantities in mammalian cells, also display a virion-like glycan profile, where the glycoprotein is extensively decorated with high-mannose glycans. 26018173 14 31 theme produced 2629:2636 arg1 version 2646:2652 a more easily produced soluble version 2615:2652 a more easily produced soluble version of the envelope glycoprotein 2615:2681 This pattern was very different from the carbohydrate profile seen for a more easily produced soluble version of the envelope glycoprotein. 26018173 3 32 dep Env 658:660 arg1 gp140 672:676 gp140 672:676 gp140 672:676 Recent studies have shown that when Env is isolated from virions, its glycosylation profile differs significantly from that of soluble forms of Env (gp120 or gp140) predominantly used in vaccine discovery research. 26018173 3 32 dep Env 658:660 arg1 gp120 663:667 gp120 663:667 gp120 663:667 Recent studies have shown that when Env is isolated from virions, its glycosylation profile differs significantly from that of soluble forms of Env (gp120 or gp140) predominantly used in vaccine discovery research. 26018173 5 33 theme detail 1116:1121 arg1 level 1097:1101 an unprecedented level 1080:1101 an unprecedented level of molecular detail regarding membrane Env glycosylation and its heterogeneity 1080:1180 Additionally, because we characterized the glycosylation with a high-fidelity profiling method, glycopeptide analysis, an unprecedented level of molecular detail regarding membrane Env glycosylation and its heterogeneity is presented. 26018173 10 34 theme Env 1856:1858 arg1 glycosylation 1860:1872 Env glycosylation 1856:1872 Env glycosylation 1856:1872 These findings provide new insight into Env glycosylation and clarify key molecular-level differences between membrane-anchored Env and soluble gp140. 26018173 11 35 gly glycoproteins 2124:2136 arg1 glycoproteins 2124:2136 the surface envelope glycoproteins 2103:2136 the surface envelope glycoproteins on the membrane of the virus 2103:2165 IMPORTANCE: A vaccine that protects against human immunodeficiency virus type 1 (HIV-1) infection should elicit antibodies that bind to the surface envelope glycoproteins on the membrane of the virus. 26018173 8 36 theme site-level 1516:1525 arg1 studies 1527:1533 These site-level studies 1510:1533 These site-level studies 1510:1533 These site-level studies are important for understanding antibody-glycan interactions on native Env trimers. 26018173 0 37 theme Glycoprotein 87:98 arg1 Profiles 42:49 the Glycosylation Profiles 24:49 the Glycosylation Profiles of Membrane-Anchored HIV-1 Envelope Glycoprotein Trimers and Soluble gp140 24:124 Comparative Analysis of the Glycosylation Profiles of Membrane-Anchored HIV-1 Envelope Glycoprotein Trimers and Soluble gp140. 26018173 5 38 theme membrane 1133:1140 arg1 glycosylation 1146:1158 membrane Env glycosylation and its heterogeneity 1133:1180 glycosylation 1146:1158 Additionally, because we characterized the glycosylation with a high-fidelity profiling method, glycopeptide analysis, an unprecedented level of molecular detail regarding membrane Env glycosylation and its heterogeneity is presented. 26018173 1 39 theme HIV-1 168:172 arg1 glycoprotein 184:195 The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein 127:195 The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) 127:201 The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) trimer, which consists of the gp120 and gp41 subunits, is the focus of multiple strategies for vaccine development. 26018173 1 39 theme HIV-1 168:172 arg1 focus 265:269 the focus 261:269 the focus of multiple strategies for vaccine development 261:316 The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) trimer, which consists of the gp120 and gp41 subunits, is the focus of multiple strategies for vaccine development. 26018173 1 39 theme HIV-1 168:172 arg1 Env 198:200 Env 198:200 Env 198:200 The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) trimer, which consists of the gp120 and gp41 subunits, is the focus of multiple strategies for vaccine development. 26018173 5 40 theme unprecedented 1083:1095 arg1 level 1097:1101 an unprecedented level 1080:1101 an unprecedented level of molecular detail regarding membrane Env glycosylation and its heterogeneity 1080:1180 Additionally, because we characterized the glycosylation with a high-fidelity profiling method, glycopeptide analysis, an unprecedented level of molecular detail regarding membrane Env glycosylation and its heterogeneity is presented. 26018173 3 41 attach isolated 557:564 arg2 Env 550:552 Env 550:552 Env 550:552 Recent studies have shown that when Env is isolated from virions, its glycosylation profile differs significantly from that of soluble forms of Env (gp120 or gp140) predominantly used in vaccine discovery research. 26018173 3 41 attach isolated 557:564 arg1 virions 571:577 virions 571:577 virions 571:577 Recent studies have shown that when Env is isolated from virions, its glycosylation profile differs significantly from that of soluble forms of Env (gp120 or gp140) predominantly used in vaccine discovery research. 26018173 1 42 theme virus 154:158 arg1 glycoprotein 184:195 The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein 127:195 The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) 127:201 The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) trimer, which consists of the gp120 and gp41 subunits, is the focus of multiple strategies for vaccine development. 26018173 1 42 theme virus 154:158 arg1 focus 265:269 the focus 261:269 the focus of multiple strategies for vaccine development 261:316 The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) trimer, which consists of the gp120 and gp41 subunits, is the focus of multiple strategies for vaccine development. 26018173 1 42 theme virus 154:158 arg1 Env 198:200 Env 198:200 Env 198:200 The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) trimer, which consists of the gp120 and gp41 subunits, is the focus of multiple strategies for vaccine development. 26018173 4 43 theme exogenous 747:755 arg1 Envs 775:778 exogenous membrane-anchored Envs 747:778 exogenous membrane-anchored Envs 747:778 Here we show that exogenous membrane-anchored Envs, which can be produced in large quantities in mammalian cells, also display a virion-like glycan profile, where the glycoprotein is extensively decorated with high-mannose glycans. 26018173 0 44 theme gp140 120:124 arg1 Profiles 42:49 the Glycosylation Profiles 24:49 the Glycosylation Profiles of Membrane-Anchored HIV-1 Envelope Glycoprotein Trimers and Soluble gp140 24:124 Comparative Analysis of the Glycosylation Profiles of Membrane-Anchored HIV-1 Envelope Glycoprotein Trimers and Soluble gp140. 26018173 4 45 from quantities 812:821 arg1 cells 836:840 mammalian cells 826:840 mammalian cells 826:840 Here we show that exogenous membrane-anchored Envs, which can be produced in large quantities in mammalian cells, also display a virion-like glycan profile, where the glycoprotein is extensively decorated with high-mannose glycans. 26018173 0 46 theme Profiles 42:49 arg1 Analysis 12:19 Comparative Analysis 0:19 Comparative Analysis of the Glycosylation Profiles of Membrane-Anchored HIV-1 Envelope Glycoprotein Trimers and Soluble gp140. 0:125 Comparative Analysis of the Glycosylation Profiles of Membrane-Anchored HIV-1 Envelope Glycoprotein Trimers and Soluble gp140. 26018173 8 47 theme antibody-glycan 1567:1581 arg1 interactions 1583:1594 antibody-glycan interactions 1567:1594 antibody-glycan interactions on native Env trimers 1567:1616 These site-level studies are important for understanding antibody-glycan interactions on native Env trimers. 26018173 15 48 theme glycans 2739:2745 arg1 characterization 2715:2730 a detailed characterization 2704:2730 a detailed characterization of the glycans on the natural membrane envelope glycoproteins of HIV-1, a carbohydrate profile that would be desirable to mimic with a vaccine 2704:2873 Our results provide a detailed characterization of the glycans on the natural membrane envelope glycoproteins of HIV-1, a carbohydrate profile that would be desirable to mimic with a vaccine. 26018173 0 49 theme Comparative 0:10 arg1 Analysis 12:19 Comparative Analysis 0:19 Comparative Analysis of the Glycosylation Profiles of Membrane-Anchored HIV-1 Envelope Glycoprotein Trimers and Soluble gp140. 0:125 Comparative Analysis of the Glycosylation Profiles of Membrane-Anchored HIV-1 Envelope Glycoprotein Trimers and Soluble gp140. 26018173 0 50 dep Glycoprotein 87:98 arg1 Trimers 100:106 Trimers 100:106 Trimers 100:106 Comparative Analysis of the Glycosylation Profiles of Membrane-Anchored HIV-1 Envelope Glycoprotein Trimers and Soluble gp140. 26018173 11 51 theme type 2040:2043 arg1 infection 2055:2063 human immunodeficiency virus type 1 (HIV-1) infection 2011:2063 human immunodeficiency virus type 1 (HIV-1) infection 2011:2063 IMPORTANCE: A vaccine that protects against human immunodeficiency virus type 1 (HIV-1) infection should elicit antibodies that bind to the surface envelope glycoproteins on the membrane of the virus. 26018173 14 52 theme carbohydrate 2585:2596 arg1 profile 2598:2604 the carbohydrate profile 2581:2604 the carbohydrate profile seen for a more easily produced soluble version of the envelope glycoprotein 2581:2681 This pattern was very different from the carbohydrate profile seen for a more easily produced soluble version of the envelope glycoprotein. 26018173 13 53 theme many 2475:2478 arg1 glycans 2493:2499 many high-mannose glycans 2475:2499 many high-mannose glycans 2475:2499 We found that the HIV-1 membrane envelope glycoproteins have a unique pattern of carbohydrates, with many high-mannose glycans and also, in some places, complex glycans. 26018173 7 54 theme sites 1327:1331 arg1 many 1315:1318 many 1315:1318 many 1315:1318 While many of the sites contain exclusively high-mannose glycans, others retain complex glycans, resulting in a glycan profile that cannot currently be mimicked on soluble gp120 or gp140 preparations. 26018173 7 54 theme sites 1327:1331 arg1 sites 1327:1331 the sites 1323:1331 the sites 1323:1331 While many of the sites contain exclusively high-mannose glycans, others retain complex glycans, resulting in a glycan profile that cannot currently be mimicked on soluble gp120 or gp140 preparations. 26018173 2 55 theme binding 451:457 arg1 epitopes 459:466 binding epitopes 451:466 binding epitopes for numerous broadly neutralizing antibodies 451:511 Extensive Env glycosylation provides HIV-1 with protection from the immune system, yet the glycans are also essential components of binding epitopes for numerous broadly neutralizing antibodies. 26018173 8 56 theme Env 1606:1608 arg1 trimers 1610:1616 native Env trimers 1599:1616 native Env trimers 1599:1616 These site-level studies are important for understanding antibody-glycan interactions on native Env trimers. 26018173 3 57 theme soluble 641:647 arg1 forms 649:653 soluble forms 641:653 soluble forms of Env (gp120 or gp140) predominantly used in vaccine discovery research 641:726 Recent studies have shown that when Env is isolated from virions, its glycosylation profile differs significantly from that of soluble forms of Env (gp120 or gp140) predominantly used in vaccine discovery research. 26018173 1 58 dep glycoprotein 184:195 arg1 trimer 203:208 trimer 203:208 trimer 203:208 The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) trimer, which consists of the gp120 and gp41 subunits, is the focus of multiple strategies for vaccine development. 26018173 0 59 theme Glycosylation 28:40 arg1 Profiles 42:49 the Glycosylation Profiles 24:49 the Glycosylation Profiles of Membrane-Anchored HIV-1 Envelope Glycoprotein Trimers and Soluble gp140 24:124 Comparative Analysis of the Glycosylation Profiles of Membrane-Anchored HIV-1 Envelope Glycoprotein Trimers and Soluble gp140. 26018173 15 60 theme envelope 2771:2778 arg1 profile 2819:2825 a carbohydrate profile 2804:2825 a carbohydrate profile that would be desirable to mimic with a vaccine 2804:2873 Our results provide a detailed characterization of the glycans on the natural membrane envelope glycoproteins of HIV-1, a carbohydrate profile that would be desirable to mimic with a vaccine. 26018173 15 60 theme envelope 2771:2778 arg1 desirable 2841:2849 desirable 2841:2849 desirable 2841:2849 Our results provide a detailed characterization of the glycans on the natural membrane envelope glycoproteins of HIV-1, a carbohydrate profile that would be desirable to mimic with a vaccine. 26018173 15 60 theme envelope 2771:2778 arg1 glycoproteins 2780:2792 the natural membrane envelope glycoproteins 2750:2792 the natural membrane envelope glycoproteins of HIV-1 2750:2801 Our results provide a detailed characterization of the glycans on the natural membrane envelope glycoproteins of HIV-1, a carbohydrate profile that would be desirable to mimic with a vaccine. 26018173 13 61 theme unique 2437:2442 arg1 pattern 2444:2450 a unique pattern 2435:2450 a unique pattern of carbohydrates, with many high-mannose glycans 2435:2499 We found that the HIV-1 membrane envelope glycoproteins have a unique pattern of carbohydrates, with many high-mannose glycans and also, in some places, complex glycans. 26018173 4 62 theme high-mannose 939:950 arg1 glycans 952:958 high-mannose glycans 939:958 high-mannose glycans 939:958 Here we show that exogenous membrane-anchored Envs, which can be produced in large quantities in mammalian cells, also display a virion-like glycan profile, where the glycoprotein is extensively decorated with high-mannose glycans. 26018173 2 63 theme Extensive 319:327 arg1 glycosylation 333:345 Extensive Env glycosylation 319:345 Extensive Env glycosylation 319:345 Extensive Env glycosylation provides HIV-1 with protection from the immune system, yet the glycans are also essential components of binding epitopes for numerous broadly neutralizing antibodies. 26018173 15 64 theme natural 2754:2760 arg1 profile 2819:2825 a carbohydrate profile 2804:2825 a carbohydrate profile that would be desirable to mimic with a vaccine 2804:2873 Our results provide a detailed characterization of the glycans on the natural membrane envelope glycoproteins of HIV-1, a carbohydrate profile that would be desirable to mimic with a vaccine. 26018173 15 64 theme natural 2754:2760 arg1 desirable 2841:2849 desirable 2841:2849 desirable 2841:2849 Our results provide a detailed characterization of the glycans on the natural membrane envelope glycoproteins of HIV-1, a carbohydrate profile that would be desirable to mimic with a vaccine. 26018173 15 64 theme natural 2754:2760 arg1 glycoproteins 2780:2792 the natural membrane envelope glycoproteins 2750:2792 the natural membrane envelope glycoproteins of HIV-1 2750:2801 Our results provide a detailed characterization of the glycans on the natural membrane envelope glycoproteins of HIV-1, a carbohydrate profile that would be desirable to mimic with a vaccine. 26018173 1 65 theme strategies 283:292 arg1 glycoprotein 184:195 The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein 127:195 The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) 127:201 The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) trimer, which consists of the gp120 and gp41 subunits, is the focus of multiple strategies for vaccine development. 26018173 1 65 theme strategies 283:292 arg1 focus 265:269 the focus 261:269 the focus of multiple strategies for vaccine development 261:316 The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) trimer, which consists of the gp120 and gp41 subunits, is the focus of multiple strategies for vaccine development. 26018173 1 66 theme vaccine 298:304 arg1 development 306:316 vaccine development 298:316 vaccine development 298:316 The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) trimer, which consists of the gp120 and gp41 subunits, is the focus of multiple strategies for vaccine development. 26018173 9 67 theme observed 1651:1658 arg1 T606 1689:1692 T606 1689:1692 T606 1689:1692 Additionally, we report a newly observed O-linked glycosylation site, T606, and we show that the full O-linked glycosylation profile of membrane-associated Env is similar to that of soluble gp140. 26018173 9 67 theme observed 1651:1658 arg1 site 1683:1686 a newly observed O-linked glycosylation site 1643:1686 a newly observed O-linked glycosylation site 1643:1686 Additionally, we report a newly observed O-linked glycosylation site, T606, and we show that the full O-linked glycosylation profile of membrane-associated Env is similar to that of soluble gp140. 26018173 2 68 with HIV-1 356:360 arg1 protection 367:376 protection 367:376 protection from the immune system 367:399 Extensive Env glycosylation provides HIV-1 with protection from the immune system, yet the glycans are also essential components of binding epitopes for numerous broadly neutralizing antibodies. 26018173 9 69 theme glycosylation 1669:1681 arg1 T606 1689:1692 T606 1689:1692 T606 1689:1692 Additionally, we report a newly observed O-linked glycosylation site, T606, and we show that the full O-linked glycosylation profile of membrane-associated Env is similar to that of soluble gp140. 26018173 9 69 theme glycosylation 1669:1681 arg1 site 1683:1686 a newly observed O-linked glycosylation site 1643:1686 a newly observed O-linked glycosylation site 1643:1686 Additionally, we report a newly observed O-linked glycosylation site, T606, and we show that the full O-linked glycosylation profile of membrane-associated Env is similar to that of soluble gp140. 26018173 2 70 from system 394:399 arg1 protection 367:376 protection 367:376 protection from the immune system 367:399 Extensive Env glycosylation provides HIV-1 with protection from the immune system, yet the glycans are also essential components of binding epitopes for numerous broadly neutralizing antibodies. 26018173 10 71 theme membrane-anchored 1926:1942 arg1 Env 1944:1946 membrane-anchored Env 1926:1946 membrane-anchored Env 1926:1946 These findings provide new insight into Env glycosylation and clarify key molecular-level differences between membrane-anchored Env and soluble gp140. 26018173 12 72 theme carbohydrates 2221:2233 arg1 coat 2213:2216 an extensive coat 2200:2216 an extensive coat of carbohydrates (glycans), some of which are recognized by virus-neutralizing antibodies and some of which protect the virus from neutralizing antibodies 2200:2371 The envelope glycoproteins have an extensive coat of carbohydrates (glycans), some of which are recognized by virus-neutralizing antibodies and some of which protect the virus from neutralizing antibodies. 26018173 6 73 gly glycosylation 1201:1213 arg2 site 1215:1218 Each glycosylation site 1196:1218 Each glycosylation site 1196:1218 Each glycosylation site was characterized individually, with about 500 glycoforms characterized per Env protein. 26018173 1 74 theme gp120 233:237 arg1 subunits 248:255 the gp120 and gp41 subunits 229:255 subunits 248:255 The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) trimer, which consists of the gp120 and gp41 subunits, is the focus of multiple strategies for vaccine development. 26018173 7 75 theme gp140 1490:1494 arg1 preparations 1496:1507 gp140 preparations 1490:1507 gp140 preparations 1490:1507 While many of the sites contain exclusively high-mannose glycans, others retain complex glycans, resulting in a glycan profile that cannot currently be mimicked on soluble gp120 or gp140 preparations. 26018173 10 76 theme key 1886:1888 arg1 differences 1906:1916 key molecular-level differences 1886:1916 key molecular-level differences between membrane-anchored Env and soluble gp140 1886:1964 These findings provide new insight into Env glycosylation and clarify key molecular-level differences between membrane-anchored Env and soluble gp140. 26018173 11 77 dep IMPORTANCE 1967:1976 arg1 vaccine 1981:1987 A vaccine 1979:1987 IMPORTANCE: A vaccine that protects against human immunodeficiency virus type 1 (HIV-1) infection 1967:2063 IMPORTANCE: A vaccine that protects against human immunodeficiency virus type 1 (HIV-1) infection should elicit antibodies that bind to the surface envelope glycoproteins on the membrane of the virus. 26018173 1 78 theme gp41 243:246 arg1 subunits 248:255 the gp120 and gp41 subunits 229:255 subunits 248:255 The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) trimer, which consists of the gp120 and gp41 subunits, is the focus of multiple strategies for vaccine development. 26018173 11 79 theme virus 2161:2165 arg1 membrane 2145:2152 the membrane 2141:2152 the membrane of the virus 2141:2165 IMPORTANCE: A vaccine that protects against human immunodeficiency virus type 1 (HIV-1) infection should elicit antibodies that bind to the surface envelope glycoproteins on the membrane of the virus. 26018173 6 80 theme Env 1296:1298 arg1 protein 1300:1306 Env protein 1296:1306 Env protein 1296:1306 Each glycosylation site was characterized individually, with about 500 glycoforms characterized per Env protein. 26018173 13 81 gly glycoproteins 2416:2428 arg1 glycoproteins 2416:2428 the HIV-1 membrane envelope glycoproteins 2388:2428 the HIV-1 membrane envelope glycoproteins 2388:2428 We found that the HIV-1 membrane envelope glycoproteins have a unique pattern of carbohydrates, with many high-mannose glycans and also, in some places, complex glycans. 26018173 3 82 theme vaccine 701:707 arg1 research 719:726 vaccine discovery research 701:726 vaccine discovery research 701:726 Recent studies have shown that when Env is isolated from virions, its glycosylation profile differs significantly from that of soluble forms of Env (gp120 or gp140) predominantly used in vaccine discovery research. 26018173 4 83 theme large 806:810 arg1 quantities 812:821 large quantities 806:821 large quantities in mammalian cells 806:840 Here we show that exogenous membrane-anchored Envs, which can be produced in large quantities in mammalian cells, also display a virion-like glycan profile, where the glycoprotein is extensively decorated with high-mannose glycans. 26018173 12 84 theme envelope 2172:2179 arg1 glycoproteins 2181:2193 The envelope glycoproteins 2168:2193 The envelope glycoproteins 2168:2193 The envelope glycoproteins have an extensive coat of carbohydrates (glycans), some of which are recognized by virus-neutralizing antibodies and some of which protect the virus from neutralizing antibodies. 26018173 9 85 theme soluble 1801:1807 arg1 gp140 1809:1813 soluble gp140 1801:1813 soluble gp140 1801:1813 Additionally, we report a newly observed O-linked glycosylation site, T606, and we show that the full O-linked glycosylation profile of membrane-associated Env is similar to that of soluble gp140. 26018173 9 86 theme full 1716:1719 arg1 profile 1744:1750 the full O-linked glycosylation profile 1712:1750 the full O-linked glycosylation profile of membrane-associated Env 1712:1777 Additionally, we report a newly observed O-linked glycosylation site, T606, and we show that the full O-linked glycosylation profile of membrane-associated Env is similar to that of soluble gp140. 26018173 9 86 theme full 1716:1719 arg1 similar 1782:1788 similar 1782:1788 similar 1782:1788 Additionally, we report a newly observed O-linked glycosylation site, T606, and we show that the full O-linked glycosylation profile of membrane-associated Env is similar to that of soluble gp140. 26018173 10 87 theme soluble 1952:1958 arg1 gp140 1960:1964 soluble gp140 1952:1964 soluble gp140 1952:1964 These findings provide new insight into Env glycosylation and clarify key molecular-level differences between membrane-anchored Env and soluble gp140. 26018173 9 88 theme glycosylation 1730:1742 arg1 profile 1744:1750 the full O-linked glycosylation profile 1712:1750 the full O-linked glycosylation profile of membrane-associated Env 1712:1777 Additionally, we report a newly observed O-linked glycosylation site, T606, and we show that the full O-linked glycosylation profile of membrane-associated Env is similar to that of soluble gp140. 26018173 9 88 theme glycosylation 1730:1742 arg1 similar 1782:1788 similar 1782:1788 similar 1782:1788 Additionally, we report a newly observed O-linked glycosylation site, T606, and we show that the full O-linked glycosylation profile of membrane-associated Env is similar to that of soluble gp140. 26018173 7 89 theme glycan 1421:1426 arg1 profile 1428:1434 a glycan profile 1419:1434 a glycan profile that cannot currently be mimicked on soluble gp120 or gp140 preparations 1419:1507 While many of the sites contain exclusively high-mannose glycans, others retain complex glycans, resulting in a glycan profile that cannot currently be mimicked on soluble gp120 or gp140 preparations. 26018173 12 90 gly glycoproteins 2181:2193 arg1 glycoproteins 2181:2193 The envelope glycoproteins 2168:2193 The envelope glycoproteins 2168:2193 The envelope glycoproteins have an extensive coat of carbohydrates (glycans), some of which are recognized by virus-neutralizing antibodies and some of which protect the virus from neutralizing antibodies. 26018173 11 91 theme immunodeficiency 2017:2032 arg1 type 2040:2043 human immunodeficiency virus type 1 2011:2045 human immunodeficiency virus type 1 (HIV-1) infection 2011:2063 IMPORTANCE: A vaccine that protects against human immunodeficiency virus type 1 (HIV-1) infection should elicit antibodies that bind to the surface envelope glycoproteins on the membrane of the virus. 26018173 11 91 theme immunodeficiency 2017:2032 arg1 HIV-1 2048:2052 HIV-1 2048:2052 HIV-1 2048:2052 IMPORTANCE: A vaccine that protects against human immunodeficiency virus type 1 (HIV-1) infection should elicit antibodies that bind to the surface envelope glycoproteins on the membrane of the virus. 26018173 14 92 theme envelope 2661:2668 arg1 glycoprotein 2670:2681 the envelope glycoprotein 2657:2681 the envelope glycoprotein 2657:2681 This pattern was very different from the carbohydrate profile seen for a more easily produced soluble version of the envelope glycoprotein. 26018173 11 93 theme surface 2107:2113 arg1 glycoproteins 2124:2136 the surface envelope glycoproteins 2103:2136 the surface envelope glycoproteins on the membrane of the virus 2103:2165 IMPORTANCE: A vaccine that protects against human immunodeficiency virus type 1 (HIV-1) infection should elicit antibodies that bind to the surface envelope glycoproteins on the membrane of the virus. 26018173 13 94 with carbohydrates 2455:2467 arg1 glycans 2493:2499 many high-mannose glycans 2475:2499 many high-mannose glycans 2475:2499 We found that the HIV-1 membrane envelope glycoproteins have a unique pattern of carbohydrates, with many high-mannose glycans and also, in some places, complex glycans. 26018173 15 95 theme detailed 2706:2713 arg1 characterization 2715:2730 a detailed characterization 2704:2730 a detailed characterization of the glycans on the natural membrane envelope glycoproteins of HIV-1, a carbohydrate profile that would be desirable to mimic with a vaccine 2704:2873 Our results provide a detailed characterization of the glycans on the natural membrane envelope glycoproteins of HIV-1, a carbohydrate profile that would be desirable to mimic with a vaccine. 26018173 10 96 theme new 1839:1841 arg1 insight 1843:1849 new insight 1839:1849 new insight into Env glycosylation 1839:1872 These findings provide new insight into Env glycosylation and clarify key molecular-level differences between membrane-anchored Env and soluble gp140. 26018173 7 97 dep cannot 1441:1446 arg1 mimicked 1461:1468 mimicked 1461:1468 cannot currently be mimicked on soluble gp120 or gp140 preparations 1441:1507 While many of the sites contain exclusively high-mannose glycans, others retain complex glycans, resulting in a glycan profile that cannot currently be mimicked on soluble gp120 or gp140 preparations. 26018173 9 98 theme Env 1775:1777 arg1 profile 1744:1750 the full O-linked glycosylation profile 1712:1750 the full O-linked glycosylation profile of membrane-associated Env 1712:1777 Additionally, we report a newly observed O-linked glycosylation site, T606, and we show that the full O-linked glycosylation profile of membrane-associated Env is similar to that of soluble gp140. 26018173 9 98 theme Env 1775:1777 arg1 similar 1782:1788 similar 1782:1788 similar 1782:1788 Additionally, we report a newly observed O-linked glycosylation site, T606, and we show that the full O-linked glycosylation profile of membrane-associated Env is similar to that of soluble gp140. 26018173 7 99 contain contain 1333:1339 arg2 glycans 1366:1372 high-mannose glycans 1353:1372 high-mannose glycans 1353:1372 While many of the sites contain exclusively high-mannose glycans, others retain complex glycans, resulting in a glycan profile that cannot currently be mimicked on soluble gp120 or gp140 preparations. 26018173 7 99 contain contain 1333:1339 arg1 many 1315:1318 many 1315:1318 many 1315:1318 While many of the sites contain exclusively high-mannose glycans, others retain complex glycans, resulting in a glycan profile that cannot currently be mimicked on soluble gp120 or gp140 preparations. 26018173 7 99 contain contain 1333:1339 arg1 sites 1327:1331 the sites 1323:1331 the sites 1323:1331 While many of the sites contain exclusively high-mannose glycans, others retain complex glycans, resulting in a glycan profile that cannot currently be mimicked on soluble gp120 or gp140 preparations. 26018173 1 100 theme immunodeficiency 137:152 arg1 glycoprotein 184:195 The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein 127:195 The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) 127:201 The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) trimer, which consists of the gp120 and gp41 subunits, is the focus of multiple strategies for vaccine development. 26018173 1 100 theme immunodeficiency 137:152 arg1 focus 265:269 the focus 261:269 the focus of multiple strategies for vaccine development 261:316 The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) trimer, which consists of the gp120 and gp41 subunits, is the focus of multiple strategies for vaccine development. 26018173 1 100 theme immunodeficiency 137:152 arg1 Env 198:200 Env 198:200 Env 198:200 The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) trimer, which consists of the gp120 and gp41 subunits, is the focus of multiple strategies for vaccine development. 26018173 14 101 theme soluble 2638:2644 arg1 version 2646:2652 a more easily produced soluble version 2615:2652 a more easily produced soluble version of the envelope glycoprotein 2615:2681 This pattern was very different from the carbohydrate profile seen for a more easily produced soluble version of the envelope glycoprotein. 26018173 4 102 theme glycan 870:875 arg1 profile 877:883 a virion-like glycan profile 856:883 a virion-like glycan profile 856:883 Here we show that exogenous membrane-anchored Envs, which can be produced in large quantities in mammalian cells, also display a virion-like glycan profile, where the glycoprotein is extensively decorated with high-mannose glycans. 26018173 15 103 from glycans 2739:2745 arg1 profile 2819:2825 a carbohydrate profile 2804:2825 a carbohydrate profile that would be desirable to mimic with a vaccine 2804:2873 Our results provide a detailed characterization of the glycans on the natural membrane envelope glycoproteins of HIV-1, a carbohydrate profile that would be desirable to mimic with a vaccine. 26018173 15 103 from glycans 2739:2745 arg1 desirable 2841:2849 desirable 2841:2849 desirable 2841:2849 Our results provide a detailed characterization of the glycans on the natural membrane envelope glycoproteins of HIV-1, a carbohydrate profile that would be desirable to mimic with a vaccine. 26018173 15 103 from glycans 2739:2745 arg1 glycoproteins 2780:2792 the natural membrane envelope glycoproteins 2750:2792 the natural membrane envelope glycoproteins of HIV-1 2750:2801 Our results provide a detailed characterization of the glycans on the natural membrane envelope glycoproteins of HIV-1, a carbohydrate profile that would be desirable to mimic with a vaccine. 26018173 7 104 theme complex 1389:1395 arg1 glycans 1397:1403 complex glycans 1389:1403 complex glycans 1389:1403 While many of the sites contain exclusively high-mannose glycans, others retain complex glycans, resulting in a glycan profile that cannot currently be mimicked on soluble gp120 or gp140 preparations. 26018173 0 105 theme Envelope 78:85 arg1 Glycoprotein 87:98 Membrane-Anchored HIV-1 Envelope Glycoprotein Trimers and Soluble gp140 54:124 Glycoprotein 87:98 Comparative Analysis of the Glycosylation Profiles of Membrane-Anchored HIV-1 Envelope Glycoprotein Trimers and Soluble gp140. 26018173 11 106 theme envelope 2115:2122 arg1 glycoproteins 2124:2136 the surface envelope glycoproteins 2103:2136 the surface envelope glycoproteins on the membrane of the virus 2103:2165 IMPORTANCE: A vaccine that protects against human immunodeficiency virus type 1 (HIV-1) infection should elicit antibodies that bind to the surface envelope glycoproteins on the membrane of the virus. 26018173 3 107 theme glycosylation 584:596 arg1 profile 598:604 its glycosylation profile 580:604 its glycosylation profile 580:604 Recent studies have shown that when Env is isolated from virions, its glycosylation profile differs significantly from that of soluble forms of Env (gp120 or gp140) predominantly used in vaccine discovery research. 26018173 1 108 theme type 160:163 arg1 glycoprotein 184:195 The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein 127:195 The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) 127:201 The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) trimer, which consists of the gp120 and gp41 subunits, is the focus of multiple strategies for vaccine development. 26018173 1 108 theme type 160:163 arg1 focus 265:269 the focus 261:269 the focus of multiple strategies for vaccine development 261:316 The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) trimer, which consists of the gp120 and gp41 subunits, is the focus of multiple strategies for vaccine development. 26018173 1 108 theme type 160:163 arg1 Env 198:200 Env 198:200 Env 198:200 The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) trimer, which consists of the gp120 and gp41 subunits, is the focus of multiple strategies for vaccine development. 26018173 2 109 theme numerous 472:479 arg1 antibodies 502:511 numerous broadly neutralizing antibodies 472:511 numerous broadly neutralizing antibodies 472:511 Extensive Env glycosylation provides HIV-1 with protection from the immune system, yet the glycans are also essential components of binding epitopes for numerous broadly neutralizing antibodies. 26018173 6 110 theme glycosylation 1201:1213 arg1 site 1215:1218 Each glycosylation site 1196:1218 Each glycosylation site 1196:1218 Each glycosylation site was characterized individually, with about 500 glycoforms characterized per Env protein. 26018173 13 111 from glycans 2535:2541 arg1 places 2519:2524 some places 2514:2524 some places 2514:2524 We found that the HIV-1 membrane envelope glycoproteins have a unique pattern of carbohydrates, with many high-mannose glycans and also, in some places, complex glycans. 26018173 2 112 theme epitopes 459:466 arg1 components 437:446 essential components 427:446 essential components of binding epitopes for numerous broadly neutralizing antibodies 427:511 Extensive Env glycosylation provides HIV-1 with protection from the immune system, yet the glycans are also essential components of binding epitopes for numerous broadly neutralizing antibodies. 26018173 2 112 theme epitopes 459:466 arg1 glycans 410:416 the glycans 406:416 the glycans 406:416 Extensive Env glycosylation provides HIV-1 with protection from the immune system, yet the glycans are also essential components of binding epitopes for numerous broadly neutralizing antibodies. 26018173 0 113 theme Soluble 112:118 arg1 gp140 120:124 Soluble gp140 112:124 Soluble gp140 112:124 Comparative Analysis of the Glycosylation Profiles of Membrane-Anchored HIV-1 Envelope Glycoprotein Trimers and Soluble gp140. 26018173 5 114 theme Env 1142:1144 arg1 glycosylation 1146:1158 membrane Env glycosylation and its heterogeneity 1133:1180 glycosylation 1146:1158 Additionally, because we characterized the glycosylation with a high-fidelity profiling method, glycopeptide analysis, an unprecedented level of molecular detail regarding membrane Env glycosylation and its heterogeneity is presented. 26018173 13 115 theme high-mannose 2480:2491 arg1 glycans 2493:2499 many high-mannose glycans 2475:2499 many high-mannose glycans 2475:2499 We found that the HIV-1 membrane envelope glycoproteins have a unique pattern of carbohydrates, with many high-mannose glycans and also, in some places, complex glycans. 26018173 15 116 from glycoproteins 2780:2792 arg1 characterization 2715:2730 a detailed characterization 2704:2730 a detailed characterization of the glycans on the natural membrane envelope glycoproteins of HIV-1, a carbohydrate profile that would be desirable to mimic with a vaccine 2704:2873 Our results provide a detailed characterization of the glycans on the natural membrane envelope glycoproteins of HIV-1, a carbohydrate profile that would be desirable to mimic with a vaccine. 26018173 11 117 from glycoproteins 2124:2136 arg1 membrane 2145:2152 the membrane 2141:2152 the membrane of the virus 2141:2165 IMPORTANCE: A vaccine that protects against human immunodeficiency virus type 1 (HIV-1) infection should elicit antibodies that bind to the surface envelope glycoproteins on the membrane of the virus. 26018173 7 118 theme high-mannose 1353:1364 arg1 glycans 1366:1372 high-mannose glycans 1353:1372 high-mannose glycans 1353:1372 While many of the sites contain exclusively high-mannose glycans, others retain complex glycans, resulting in a glycan profile that cannot currently be mimicked on soluble gp120 or gp140 preparations. 26018173 2 119 theme neutralizing 489:500 arg1 antibodies 502:511 numerous broadly neutralizing antibodies 472:511 numerous broadly neutralizing antibodies 472:511 Extensive Env glycosylation provides HIV-1 with protection from the immune system, yet the glycans are also essential components of binding epitopes for numerous broadly neutralizing antibodies. 26018173 12 120 theme virus-neutralizing 2278:2295 arg1 antibodies 2297:2306 virus-neutralizing antibodies 2278:2306 virus-neutralizing antibodies and some of which protect the virus from neutralizing antibodies 2278:2371 The envelope glycoproteins have an extensive coat of carbohydrates (glycans), some of which are recognized by virus-neutralizing antibodies and some of which protect the virus from neutralizing antibodies. 26018173 15 121 theme HIV-1 2797:2801 arg1 profile 2819:2825 a carbohydrate profile 2804:2825 a carbohydrate profile that would be desirable to mimic with a vaccine 2804:2873 Our results provide a detailed characterization of the glycans on the natural membrane envelope glycoproteins of HIV-1, a carbohydrate profile that would be desirable to mimic with a vaccine. 26018173 15 121 theme HIV-1 2797:2801 arg1 desirable 2841:2849 desirable 2841:2849 desirable 2841:2849 Our results provide a detailed characterization of the glycans on the natural membrane envelope glycoproteins of HIV-1, a carbohydrate profile that would be desirable to mimic with a vaccine. 26018173 15 121 theme HIV-1 2797:2801 arg1 glycoproteins 2780:2792 the natural membrane envelope glycoproteins 2750:2792 the natural membrane envelope glycoproteins of HIV-1 2750:2801 Our results provide a detailed characterization of the glycans on the natural membrane envelope glycoproteins of HIV-1, a carbohydrate profile that would be desirable to mimic with a vaccine. 26018173 5 122 theme molecular 1106:1114 arg1 detail 1116:1121 molecular detail 1106:1121 molecular detail 1106:1121 Additionally, because we characterized the glycosylation with a high-fidelity profiling method, glycopeptide analysis, an unprecedented level of molecular detail regarding membrane Env glycosylation and its heterogeneity is presented. 26018173 13 123 theme carbohydrates 2455:2467 arg1 pattern 2444:2450 a unique pattern 2435:2450 a unique pattern of carbohydrates, with many high-mannose glycans 2435:2499 We found that the HIV-1 membrane envelope glycoproteins have a unique pattern of carbohydrates, with many high-mannose glycans and also, in some places, complex glycans. 26018173 8 124 theme native 1599:1604 arg1 trimers 1610:1616 native Env trimers 1599:1616 native Env trimers 1599:1616 These site-level studies are important for understanding antibody-glycan interactions on native Env trimers. 26018173 14 125 gly glycoprotein 2670:2681 arg1 glycoprotein 2670:2681 the envelope glycoprotein 2657:2681 the envelope glycoprotein 2657:2681 This pattern was very different from the carbohydrate profile seen for a more easily produced soluble version of the envelope glycoprotein. 26018173 8 126 from interactions 1583:1594 arg1 trimers 1610:1616 native Env trimers 1599:1616 native Env trimers 1599:1616 These site-level studies are important for understanding antibody-glycan interactions on native Env trimers. 26018173 10 127 theme molecular-level 1890:1904 arg1 differences 1906:1916 key molecular-level differences 1886:1916 key molecular-level differences between membrane-anchored Env and soluble gp140 1886:1964 These findings provide new insight into Env glycosylation and clarify key molecular-level differences between membrane-anchored Env and soluble gp140. 26018173 2 128 theme immune 387:392 arg1 system 394:399 the immune system 383:399 the immune system 383:399 Extensive Env glycosylation provides HIV-1 with protection from the immune system, yet the glycans are also essential components of binding epitopes for numerous broadly neutralizing antibodies. 26018173 0 129 theme Membrane-Anchored 54:70 arg1 Glycoprotein 87:98 Membrane-Anchored HIV-1 Envelope Glycoprotein Trimers and Soluble gp140 54:124 Glycoprotein 87:98 Comparative Analysis of the Glycosylation Profiles of Membrane-Anchored HIV-1 Envelope Glycoprotein Trimers and Soluble gp140. 26018173 1 130 theme multiple 274:281 arg1 strategies 283:292 multiple strategies 274:292 multiple strategies for vaccine development 274:316 The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) trimer, which consists of the gp120 and gp41 subunits, is the focus of multiple strategies for vaccine development. 26018173 0 131 theme HIV-1 72:76 arg1 Glycoprotein 87:98 Membrane-Anchored HIV-1 Envelope Glycoprotein Trimers and Soluble gp140 54:124 Glycoprotein 87:98 Comparative Analysis of the Glycosylation Profiles of Membrane-Anchored HIV-1 Envelope Glycoprotein Trimers and Soluble gp140. 26018173 2 132 theme essential 427:435 arg1 components 437:446 essential components 427:446 essential components of binding epitopes for numerous broadly neutralizing antibodies 427:511 Extensive Env glycosylation provides HIV-1 with protection from the immune system, yet the glycans are also essential components of binding epitopes for numerous broadly neutralizing antibodies. 26018173 2 132 theme essential 427:435 arg1 glycans 410:416 the glycans 406:416 the glycans 406:416 Extensive Env glycosylation provides HIV-1 with protection from the immune system, yet the glycans are also essential components of binding epitopes for numerous broadly neutralizing antibodies. 26018173 3 133 theme Env 658:660 arg1 forms 649:653 soluble forms 641:653 soluble forms of Env (gp120 or gp140) predominantly used in vaccine discovery research 641:726 Recent studies have shown that when Env is isolated from virions, its glycosylation profile differs significantly from that of soluble forms of Env (gp120 or gp140) predominantly used in vaccine discovery research. 26018173 9 134 theme O-linked 1660:1667 arg1 T606 1689:1692 T606 1689:1692 T606 1689:1692 Additionally, we report a newly observed O-linked glycosylation site, T606, and we show that the full O-linked glycosylation profile of membrane-associated Env is similar to that of soluble gp140. 26018173 9 134 theme O-linked 1660:1667 arg1 site 1683:1686 a newly observed O-linked glycosylation site 1643:1686 a newly observed O-linked glycosylation site 1643:1686 Additionally, we report a newly observed O-linked glycosylation site, T606, and we show that the full O-linked glycosylation profile of membrane-associated Env is similar to that of soluble gp140. 26018173 15 135 theme membrane 2762:2769 arg1 profile 2819:2825 a carbohydrate profile 2804:2825 a carbohydrate profile that would be desirable to mimic with a vaccine 2804:2873 Our results provide a detailed characterization of the glycans on the natural membrane envelope glycoproteins of HIV-1, a carbohydrate profile that would be desirable to mimic with a vaccine. 26018173 15 135 theme membrane 2762:2769 arg1 desirable 2841:2849 desirable 2841:2849 desirable 2841:2849 Our results provide a detailed characterization of the glycans on the natural membrane envelope glycoproteins of HIV-1, a carbohydrate profile that would be desirable to mimic with a vaccine. 26018173 15 135 theme membrane 2762:2769 arg1 glycoproteins 2780:2792 the natural membrane envelope glycoproteins 2750:2792 the natural membrane envelope glycoproteins of HIV-1 2750:2801 Our results provide a detailed characterization of the glycans on the natural membrane envelope glycoproteins of HIV-1, a carbohydrate profile that would be desirable to mimic with a vaccine. 26018173 5 136 gly glycopeptide 1057:1068 arg2 glycopeptide 1057:1068 glycopeptide analysis 1057:1077 glycopeptide analysis 1057:1077 Additionally, because we characterized the glycosylation with a high-fidelity profiling method, glycopeptide analysis, an unprecedented level of molecular detail regarding membrane Env glycosylation and its heterogeneity is presented. 26018173 4 137 theme membrane-anchored 757:773 arg1 Envs 775:778 exogenous membrane-anchored Envs 747:778 exogenous membrane-anchored Envs 747:778 Here we show that exogenous membrane-anchored Envs, which can be produced in large quantities in mammalian cells, also display a virion-like glycan profile, where the glycoprotein is extensively decorated with high-mannose glycans. 26018173 15 138 gly glycoproteins 2780:2792 arg1 profile 2819:2825 a carbohydrate profile 2804:2825 a carbohydrate profile that would be desirable to mimic with a vaccine 2804:2873 Our results provide a detailed characterization of the glycans on the natural membrane envelope glycoproteins of HIV-1, a carbohydrate profile that would be desirable to mimic with a vaccine. 26018173 15 138 gly glycoproteins 2780:2792 arg1 desirable 2841:2849 desirable 2841:2849 desirable 2841:2849 Our results provide a detailed characterization of the glycans on the natural membrane envelope glycoproteins of HIV-1, a carbohydrate profile that would be desirable to mimic with a vaccine. 26018173 15 138 gly glycoproteins 2780:2792 arg1 glycoproteins 2780:2792 the natural membrane envelope glycoproteins 2750:2792 the natural membrane envelope glycoproteins of HIV-1 2750:2801 Our results provide a detailed characterization of the glycans on the natural membrane envelope glycoproteins of HIV-1, a carbohydrate profile that would be desirable to mimic with a vaccine. 26018173 3 139 theme Recent 514:519 arg1 studies 521:527 Recent studies 514:527 Recent studies 514:527 Recent studies have shown that when Env is isolated from virions, its glycosylation profile differs significantly from that of soluble forms of Env (gp120 or gp140) predominantly used in vaccine discovery research. 25690651 7 0 theme mutants 944:950 arg1 expression 910:919 the reduced surface expression 890:919 the reduced surface expression of the nonglycosylated mutants 890:950 This modification is required for the normal surface expression of hGPR109A, as evidenced by the reduced surface expression of the nonglycosylated mutants, hGPR109A/N17A, and the finding that hGPR109A/C19S and hGPR109A/C19T, which are N-glycosylated at Asn(17), exhibited expression similar to the wild-type receptor. 25690651 7 0 theme mutants 944:950 arg1 hGPR109A/N17A 953:965 hGPR109A/N17A 953:965 hGPR109A/N17A 953:965 This modification is required for the normal surface expression of hGPR109A, as evidenced by the reduced surface expression of the nonglycosylated mutants, hGPR109A/N17A, and the finding that hGPR109A/C19S and hGPR109A/C19T, which are N-glycosylated at Asn(17), exhibited expression similar to the wild-type receptor. 25690651 7 0 theme mutants 944:950 arg1 finding 976:982 the finding 972:982 the finding that hGPR109A/C19S and hGPR109A/C19T, which are N-glycosylated at Asn(17), exhibited expression similar to the wild-type receptor 972:1112 This modification is required for the normal surface expression of hGPR109A, as evidenced by the reduced surface expression of the nonglycosylated mutants, hGPR109A/N17A, and the finding that hGPR109A/C19S and hGPR109A/C19T, which are N-glycosylated at Asn(17), exhibited expression similar to the wild-type receptor. 25690651 3 1 theme N-terminal 477:486 arg1 Asn 504:506 Asn(17)-Cys(18)-Cys(19) 504:526 Asn(17)-Cys(18)-Cys(19) 504:526 We found that human GPR109A (hGPR109A) has an N-glycosylation site at Asn(17) in the N-terminal atypical motif, Asn(17)-Cys(18)-Cys(19). 25690651 3 1 theme N-terminal 477:486 arg1 motif 497:501 the N-terminal atypical motif 473:501 the N-terminal atypical motif 473:501 We found that human GPR109A (hGPR109A) has an N-glycosylation site at Asn(17) in the N-terminal atypical motif, Asn(17)-Cys(18)-Cys(19). 25690651 1 2 theme proteins 253:260 arg1 folding 220:226 the proper folding 209:226 the proper folding of secreted and membrane proteins, including GPCRs 209:277 Asparagine-linked glycosylation (N-glycosylation) is necessary for the proper folding of secreted and membrane proteins, including GPCRs. 25690651 5 3 theme -Cys 642:645 arg1 sequence 651:658 Asn(17)-Cys(18)-Cys(19) sequence 627:658 Asn(17)-Cys(18)-Cys(19) sequence of hGPR109A 627:670 Here we show that Asn(17)-Cys(18)-Cys(19) sequence of hGPR109A possesses 2 biologic roles. 25690651 3 4 theme atypical 488:495 arg1 Asn 504:506 Asn(17)-Cys(18)-Cys(19) 504:526 Asn(17)-Cys(18)-Cys(19) 504:526 We found that human GPR109A (hGPR109A) has an N-glycosylation site at Asn(17) in the N-terminal atypical motif, Asn(17)-Cys(18)-Cys(19). 25690651 3 4 theme atypical 488:495 arg1 motif 497:501 the N-terminal atypical motif 473:501 the N-terminal atypical motif 473:501 We found that human GPR109A (hGPR109A) has an N-glycosylation site at Asn(17) in the N-terminal atypical motif, Asn(17)-Cys(18)-Cys(19). 25690651 7 5 dep finding 976:982 arg1 exhibited 1059:1067 exhibited 1059:1067 exhibited expression similar to the wild-type receptor 1059:1112 This modification is required for the normal surface expression of hGPR109A, as evidenced by the reduced surface expression of the nonglycosylated mutants, hGPR109A/N17A, and the finding that hGPR109A/C19S and hGPR109A/C19T, which are N-glycosylated at Asn(17), exhibited expression similar to the wild-type receptor. 25690651 0 6 theme normal 82:87 arg1 expression 102:111 normal cell surface expression 82:111 normal cell surface expression 82:111 The atypical N-glycosylation motif, Asn-Cys-Cys, in human GPR109A is required for normal cell surface expression and intracellular signaling. 25690651 2 7 theme many 286:289 arg1 GPCRs 291:295 many GPCRs 286:295 many GPCRs 286:295 Thus, many GPCRs possess the N-glycosylation motif Asn-X-Ser/Thr at their N-termini and/or extracellular loops. 25690651 7 8 theme nonglycosylated 928:942 arg1 mutants 944:950 the nonglycosylated mutants 924:950 the nonglycosylated mutants 924:950 This modification is required for the normal surface expression of hGPR109A, as evidenced by the reduced surface expression of the nonglycosylated mutants, hGPR109A/N17A, and the finding that hGPR109A/C19S and hGPR109A/C19T, which are N-glycosylated at Asn(17), exhibited expression similar to the wild-type receptor. 25690651 11 9 theme motif 1474:1478 arg1 19 1500:1501 19 1500:1501 19 1500:1501 Together, these results suggest that the atypical motif Asn(17)-Cys(18)-Cys(19) is crucial for the normal surface trafficking and function of hGPR109A. 25690651 11 9 theme motif 1474:1478 arg1 crucial 1507:1513 crucial 1507:1513 crucial 1507:1513 Together, these results suggest that the atypical motif Asn(17)-Cys(18)-Cys(19) is crucial for the normal surface trafficking and function of hGPR109A. 25690651 11 9 theme motif 1474:1478 arg1 -Cys 1487:1490 the atypical motif Asn(17)-Cys(18)-Cys 1461:1498 the atypical motif Asn(17)-Cys(18)-Cys(19) 1461:1502 Together, these results suggest that the atypical motif Asn(17)-Cys(18)-Cys(19) is crucial for the normal surface trafficking and function of hGPR109A. 25690651 7 10 theme similar 1080:1086 arg1 expression 1069:1078 expression 1069:1078 expression similar to the wild-type receptor 1069:1112 This modification is required for the normal surface expression of hGPR109A, as evidenced by the reduced surface expression of the nonglycosylated mutants, hGPR109A/N17A, and the finding that hGPR109A/C19S and hGPR109A/C19T, which are N-glycosylated at Asn(17), exhibited expression similar to the wild-type receptor. 25690651 0 11 theme surface 94:100 arg1 expression 102:111 normal cell surface expression 82:111 normal cell surface expression 82:111 The atypical N-glycosylation motif, Asn-Cys-Cys, in human GPR109A is required for normal cell surface expression and intracellular signaling. 25690651 9 12 theme Cys 1212:1214 arg1 Substitution 1196:1207 Substitution 1196:1207 Substitution of Cys(18) or Cys(19) residue to Ala 1196:1244 Substitution of Cys(18) or Cys(19) residue to Ala impaired Gi-mediated signaling via hGPR109A. 25690651 0 13 theme cell 89:92 arg1 expression 102:111 normal cell surface expression 82:111 normal cell surface expression 82:111 The atypical N-glycosylation motif, Asn-Cys-Cys, in human GPR109A is required for normal cell surface expression and intracellular signaling. 25690651 8 14 theme -Cys 1136:1139 arg1 indispensable 1159:1171 indispensable 1159:1171 indispensable 1159:1171 Second, the X-Cys(18)-Cys(19) dicysteine is indispensable for hGPR109A function. 25690651 8 14 theme -Cys 1136:1139 arg1 dicysteine 1145:1154 the X-Cys(18)-Cys(19) dicysteine 1123:1154 the X-Cys(18)-Cys(19) dicysteine 1123:1154 Second, the X-Cys(18)-Cys(19) dicysteine is indispensable for hGPR109A function. 25690651 3 15 theme N-glycosylation 438:452 arg1 site 454:457 an N-glycosylation site 435:457 an N-glycosylation site at Asn(17) 435:468 We found that human GPR109A (hGPR109A) has an N-glycosylation site at Asn(17) in the N-terminal atypical motif, Asn(17)-Cys(18)-Cys(19). 25690651 0 16 theme atypical 4:11 arg1 Asn-Cys-Cys 36:46 Asn-Cys-Cys 36:46 Asn-Cys-Cys 36:46 The atypical N-glycosylation motif, Asn-Cys-Cys, in human GPR109A is required for normal cell surface expression and intracellular signaling. 25690651 0 16 theme atypical 4:11 arg1 motif 29:33 The atypical N-glycosylation motif 0:33 The atypical N-glycosylation motif 0:33 The atypical N-glycosylation motif, Asn-Cys-Cys, in human GPR109A is required for normal cell surface expression and intracellular signaling. 25690651 11 17 theme surface 1530:1536 arg1 trafficking 1538:1548 normal surface trafficking 1523:1548 normal surface trafficking 1523:1548 Together, these results suggest that the atypical motif Asn(17)-Cys(18)-Cys(19) is crucial for the normal surface trafficking and function of hGPR109A. 25690651 7 18 theme reduced 894:900 arg1 expression 910:919 the reduced surface expression 890:919 the reduced surface expression of the nonglycosylated mutants 890:950 This modification is required for the normal surface expression of hGPR109A, as evidenced by the reduced surface expression of the nonglycosylated mutants, hGPR109A/N17A, and the finding that hGPR109A/C19S and hGPR109A/C19T, which are N-glycosylated at Asn(17), exhibited expression similar to the wild-type receptor. 25690651 2 19 from N-termini 354:362 arg1 Asn-X-Ser/Thr 331:343 Asn-X-Ser/Thr 331:343 Asn-X-Ser/Thr 331:343 Thus, many GPCRs possess the N-glycosylation motif Asn-X-Ser/Thr at their N-termini and/or extracellular loops. 25690651 2 20 theme N-glycosylation 309:323 arg1 motif 325:329 the N-glycosylation motif 305:329 the N-glycosylation motif Asn-X-Ser/Thr at their N-termini and/or extracellular loops 305:389 Thus, many GPCRs possess the N-glycosylation motif Asn-X-Ser/Thr at their N-termini and/or extracellular loops. 25690651 5 21 theme hGPR109A 663:670 arg1 sequence 651:658 Asn(17)-Cys(18)-Cys(19) sequence 627:658 Asn(17)-Cys(18)-Cys(19) sequence of hGPR109A 627:670 Here we show that Asn(17)-Cys(18)-Cys(19) sequence of hGPR109A possesses 2 biologic roles. 25690651 7 22 theme surface 902:908 arg1 expression 910:919 the reduced surface expression 890:919 the reduced surface expression of the nonglycosylated mutants 890:950 This modification is required for the normal surface expression of hGPR109A, as evidenced by the reduced surface expression of the nonglycosylated mutants, hGPR109A/N17A, and the finding that hGPR109A/C19S and hGPR109A/C19T, which are N-glycosylated at Asn(17), exhibited expression similar to the wild-type receptor. 25690651 2 23 from loops 385:389 arg1 Asn-X-Ser/Thr 331:343 Asn-X-Ser/Thr 331:343 Asn-X-Ser/Thr 331:343 Thus, many GPCRs possess the N-glycosylation motif Asn-X-Ser/Thr at their N-termini and/or extracellular loops. 25690651 11 24 theme atypical 1465:1472 arg1 19 1500:1501 19 1500:1501 19 1500:1501 Together, these results suggest that the atypical motif Asn(17)-Cys(18)-Cys(19) is crucial for the normal surface trafficking and function of hGPR109A. 25690651 11 24 theme atypical 1465:1472 arg1 crucial 1507:1513 crucial 1507:1513 crucial 1507:1513 Together, these results suggest that the atypical motif Asn(17)-Cys(18)-Cys(19) is crucial for the normal surface trafficking and function of hGPR109A. 25690651 11 24 theme atypical 1465:1472 arg1 -Cys 1487:1490 the atypical motif Asn(17)-Cys(18)-Cys 1461:1498 the atypical motif Asn(17)-Cys(18)-Cys(19) 1461:1502 Together, these results suggest that the atypical motif Asn(17)-Cys(18)-Cys(19) is crucial for the normal surface trafficking and function of hGPR109A. 25690651 7 25 theme wild-type 1095:1103 arg1 receptor 1105:1112 the wild-type receptor 1091:1112 the wild-type receptor 1091:1112 This modification is required for the normal surface expression of hGPR109A, as evidenced by the reduced surface expression of the nonglycosylated mutants, hGPR109A/N17A, and the finding that hGPR109A/C19S and hGPR109A/C19T, which are N-glycosylated at Asn(17), exhibited expression similar to the wild-type receptor. 25690651 10 26 theme extracellular 1380:1392 arg1 loops 1394:1398 the extracellular loops 1376:1398 the extracellular loops for the proper folding 1376:1421 We propose the disulfide bond formations of these residues with other Cys existed in the extracellular loops for the proper folding. 25690651 10 27 theme residues 1341:1348 arg1 formations 1321:1330 formations 1321:1330 formations of these residues with other Cys 1321:1363 We propose the disulfide bond formations of these residues with other Cys existed in the extracellular loops for the proper folding. 25690651 10 28 dep bond 1316:1319 arg1 existed 1365:1371 existed 1365:1371 existed in the extracellular loops for the proper folding 1365:1421 We propose the disulfide bond formations of these residues with other Cys existed in the extracellular loops for the proper folding. 25690651 10 29 with formations 1321:1330 arg1 Cys 1361:1363 other Cys 1355:1363 other Cys 1355:1363 We propose the disulfide bond formations of these residues with other Cys existed in the extracellular loops for the proper folding. 25690651 8 30 theme X-Cys 1127:1131 arg1 indispensable 1159:1171 indispensable 1159:1171 indispensable 1159:1171 Second, the X-Cys(18)-Cys(19) dicysteine is indispensable for hGPR109A function. 25690651 8 30 theme X-Cys 1127:1131 arg1 dicysteine 1145:1154 the X-Cys(18)-Cys(19) dicysteine 1123:1154 the X-Cys(18)-Cys(19) dicysteine 1123:1154 Second, the X-Cys(18)-Cys(19) dicysteine is indispensable for hGPR109A function. 25690651 5 31 theme biologic 684:691 arg1 roles 693:697 2 biologic roles 682:697 2 biologic roles 682:697 Here we show that Asn(17)-Cys(18)-Cys(19) sequence of hGPR109A possesses 2 biologic roles. 25690651 0 32 theme N-glycosylation 13:27 arg1 Asn-Cys-Cys 36:46 Asn-Cys-Cys 36:46 Asn-Cys-Cys 36:46 The atypical N-glycosylation motif, Asn-Cys-Cys, in human GPR109A is required for normal cell surface expression and intracellular signaling. 25690651 0 32 theme N-glycosylation 13:27 arg1 motif 29:33 The atypical N-glycosylation motif 0:33 The atypical N-glycosylation motif 0:33 The atypical N-glycosylation motif, Asn-Cys-Cys, in human GPR109A is required for normal cell surface expression and intracellular signaling. 25690651 6 33 theme atypical 781:788 arg1 motif 790:794 an atypical motif 778:794 an atypical motif 778:794 First, Asn(17)-X-Cys(19) contributed to hGPR109A N-glycosylation by acting as an atypical motif. 25690651 11 34 dep trafficking 1538:1548 arg1 the 1519:1521 the 1519:1521 the 1519:1521 Together, these results suggest that the atypical motif Asn(17)-Cys(18)-Cys(19) is crucial for the normal surface trafficking and function of hGPR109A. 25690651 7 35 gly N-glycosylated 1032:1045 arg2 17 1054:1055 17 1054:1055 17 1054:1055 This modification is required for the normal surface expression of hGPR109A, as evidenced by the reduced surface expression of the nonglycosylated mutants, hGPR109A/N17A, and the finding that hGPR109A/C19S and hGPR109A/C19T, which are N-glycosylated at Asn(17), exhibited expression similar to the wild-type receptor. 25690651 7 35 gly N-glycosylated 1032:1045 arg1 hGPR109A/C19T 1007:1019 hGPR109A/C19T 1007:1019 hGPR109A/C19T 1007:1019 This modification is required for the normal surface expression of hGPR109A, as evidenced by the reduced surface expression of the nonglycosylated mutants, hGPR109A/N17A, and the finding that hGPR109A/C19S and hGPR109A/C19T, which are N-glycosylated at Asn(17), exhibited expression similar to the wild-type receptor. 25690651 7 35 gly N-glycosylated 1032:1045 arg2 Asn 1050:1052 Asn 1050:1052 Asn(17) 1050:1056 This modification is required for the normal surface expression of hGPR109A, as evidenced by the reduced surface expression of the nonglycosylated mutants, hGPR109A/N17A, and the finding that hGPR109A/C19S and hGPR109A/C19T, which are N-glycosylated at Asn(17), exhibited expression similar to the wild-type receptor. 25690651 7 35 gly N-glycosylated 1032:1045 arg1 hGPR109A/C19S 989:1001 hGPR109A/C19S 989:1001 hGPR109A/C19S 989:1001 This modification is required for the normal surface expression of hGPR109A, as evidenced by the reduced surface expression of the nonglycosylated mutants, hGPR109A/N17A, and the finding that hGPR109A/C19S and hGPR109A/C19T, which are N-glycosylated at Asn(17), exhibited expression similar to the wild-type receptor. 25690651 11 36 theme hGPR109A 1566:1573 arg1 trafficking 1538:1548 normal surface trafficking 1523:1548 normal surface trafficking 1523:1548 Together, these results suggest that the atypical motif Asn(17)-Cys(18)-Cys(19) is crucial for the normal surface trafficking and function of hGPR109A. 25690651 11 36 theme hGPR109A 1566:1573 arg1 function 1554:1561 function 1554:1561 function 1554:1561 Together, these results suggest that the atypical motif Asn(17)-Cys(18)-Cys(19) is crucial for the normal surface trafficking and function of hGPR109A. 25690651 5 37 contain possesses 672:680 arg1 sequence 651:658 Asn(17)-Cys(18)-Cys(19) sequence 627:658 Asn(17)-Cys(18)-Cys(19) sequence of hGPR109A 627:670 Here we show that Asn(17)-Cys(18)-Cys(19) sequence of hGPR109A possesses 2 biologic roles. 25690651 5 37 contain possesses 672:680 arg2 roles 693:697 2 biologic roles 682:697 2 biologic roles 682:697 Here we show that Asn(17)-Cys(18)-Cys(19) sequence of hGPR109A possesses 2 biologic roles. 25690651 5 38 theme Asn 627:629 arg1 sequence 651:658 Asn(17)-Cys(18)-Cys(19) sequence 627:658 Asn(17)-Cys(18)-Cys(19) sequence of hGPR109A 627:670 Here we show that Asn(17)-Cys(18)-Cys(19) sequence of hGPR109A possesses 2 biologic roles. 25690651 1 39 theme proper 213:218 arg1 folding 220:226 the proper folding 209:226 the proper folding of secreted and membrane proteins, including GPCRs 209:277 Asparagine-linked glycosylation (N-glycosylation) is necessary for the proper folding of secreted and membrane proteins, including GPCRs. 25690651 0 40 theme intracellular 117:129 arg1 signaling 131:139 intracellular signaling 117:139 intracellular signaling 117:139 The atypical N-glycosylation motif, Asn-Cys-Cys, in human GPR109A is required for normal cell surface expression and intracellular signaling. 25690651 6 41 theme Asn 707:709 arg1 -X-Cys 714:719 Asn(17)-X-Cys(19) 707:723 Asn(17)-X-Cys(19) 707:723 First, Asn(17)-X-Cys(19) contributed to hGPR109A N-glycosylation by acting as an atypical motif. 25690651 7 42 theme normal 835:840 arg1 expression 850:859 the normal surface expression 831:859 the normal surface expression of hGPR109A 831:871 This modification is required for the normal surface expression of hGPR109A, as evidenced by the reduced surface expression of the nonglycosylated mutants, hGPR109A/N17A, and the finding that hGPR109A/C19S and hGPR109A/C19T, which are N-glycosylated at Asn(17), exhibited expression similar to the wild-type receptor. 25690651 4 43 theme atypical 559:566 arg1 motif 568:572 the atypical motif 555:572 the atypical motif 555:572 Why does hGPR109A require the atypical motif, rather than the typical sequence? 25690651 3 44 theme human 406:410 arg1 GPR109A 412:418 human GPR109A 406:418 human GPR109A (hGPR109A) 406:429 We found that human GPR109A (hGPR109A) has an N-glycosylation site at Asn(17) in the N-terminal atypical motif, Asn(17)-Cys(18)-Cys(19). 25690651 3 44 theme human 406:410 arg1 hGPR109A 421:428 hGPR109A 421:428 hGPR109A 421:428 We found that human GPR109A (hGPR109A) has an N-glycosylation site at Asn(17) in the N-terminal atypical motif, Asn(17)-Cys(18)-Cys(19). 25690651 2 45 contain possess 297:303 arg2 motif 325:329 the N-glycosylation motif 305:329 the N-glycosylation motif Asn-X-Ser/Thr at their N-termini and/or extracellular loops 305:389 Thus, many GPCRs possess the N-glycosylation motif Asn-X-Ser/Thr at their N-termini and/or extracellular loops. 25690651 2 45 contain possess 297:303 arg1 GPCRs 291:295 many GPCRs 286:295 many GPCRs 286:295 Thus, many GPCRs possess the N-glycosylation motif Asn-X-Ser/Thr at their N-termini and/or extracellular loops. 25690651 7 46 theme hGPR109A 864:871 arg1 expression 850:859 the normal surface expression 831:859 the normal surface expression of hGPR109A 831:871 This modification is required for the normal surface expression of hGPR109A, as evidenced by the reduced surface expression of the nonglycosylated mutants, hGPR109A/N17A, and the finding that hGPR109A/C19S and hGPR109A/C19T, which are N-glycosylated at Asn(17), exhibited expression similar to the wild-type receptor. 25690651 0 47 theme human 52:56 arg1 GPR109A 58:64 human GPR109A 52:64 human GPR109A 52:64 The atypical N-glycosylation motif, Asn-Cys-Cys, in human GPR109A is required for normal cell surface expression and intracellular signaling. 25690651 0 48 gly N-glycosylation 13:27 arg2 Asn-Cys-Cys 36:46 Asn-Cys-Cys 36:46 Asn-Cys-Cys 36:46 The atypical N-glycosylation motif, Asn-Cys-Cys, in human GPR109A is required for normal cell surface expression and intracellular signaling. 25690651 0 48 gly N-glycosylation 13:27 arg2 motif 29:33 The atypical N-glycosylation motif 0:33 The atypical N-glycosylation motif 0:33 The atypical N-glycosylation motif, Asn-Cys-Cys, in human GPR109A is required for normal cell surface expression and intracellular signaling. 25690651 7 49 theme surface 842:848 arg1 expression 850:859 the normal surface expression 831:859 the normal surface expression of hGPR109A 831:871 This modification is required for the normal surface expression of hGPR109A, as evidenced by the reduced surface expression of the nonglycosylated mutants, hGPR109A/N17A, and the finding that hGPR109A/C19S and hGPR109A/C19T, which are N-glycosylated at Asn(17), exhibited expression similar to the wild-type receptor. 25690651 9 50 theme residue 1231:1237 arg1 Ala 1242:1244 residue to Ala 1231:1244 residue to Ala 1231:1244 Substitution of Cys(18) or Cys(19) residue to Ala impaired Gi-mediated signaling via hGPR109A. 25690651 1 51 link Asparagine-linked 142:158 arg1 N-glycosylation 175:189 N-glycosylation 175:189 N-glycosylation 175:189 Asparagine-linked glycosylation (N-glycosylation) is necessary for the proper folding of secreted and membrane proteins, including GPCRs. 25690651 1 51 link Asparagine-linked 142:158 arg1 glycosylation 160:172 Asparagine-linked glycosylation 142:172 Asparagine-linked glycosylation (N-glycosylation) 142:190 Asparagine-linked glycosylation (N-glycosylation) is necessary for the proper folding of secreted and membrane proteins, including GPCRs. 25690651 6 52 theme hGPR109A 740:747 arg1 N-glycosylation 749:763 hGPR109A N-glycosylation 740:763 hGPR109A N-glycosylation 740:763 First, Asn(17)-X-Cys(19) contributed to hGPR109A N-glycosylation by acting as an atypical motif. 25690651 3 53 contain has 431:433 arg1 GPR109A 412:418 human GPR109A 406:418 human GPR109A (hGPR109A) 406:429 We found that human GPR109A (hGPR109A) has an N-glycosylation site at Asn(17) in the N-terminal atypical motif, Asn(17)-Cys(18)-Cys(19). 25690651 3 53 contain has 431:433 arg2 site 454:457 an N-glycosylation site 435:457 an N-glycosylation site at Asn(17) 435:468 We found that human GPR109A (hGPR109A) has an N-glycosylation site at Asn(17) in the N-terminal atypical motif, Asn(17)-Cys(18)-Cys(19). 25690651 3 53 contain has 431:433 arg1 hGPR109A 421:428 hGPR109A 421:428 hGPR109A 421:428 We found that human GPR109A (hGPR109A) has an N-glycosylation site at Asn(17) in the N-terminal atypical motif, Asn(17)-Cys(18)-Cys(19). 25690651 8 54 theme hGPR109A 1177:1184 arg1 function 1186:1193 hGPR109A function 1177:1193 hGPR109A function 1177:1193 Second, the X-Cys(18)-Cys(19) dicysteine is indispensable for hGPR109A function. 25690651 3 55 from Asn 462:464 arg1 site 454:457 an N-glycosylation site 435:457 an N-glycosylation site at Asn(17) 435:468 We found that human GPR109A (hGPR109A) has an N-glycosylation site at Asn(17) in the N-terminal atypical motif, Asn(17)-Cys(18)-Cys(19). 25690651 10 56 theme disulfide 1306:1314 arg1 bond 1316:1319 the disulfide bond 1302:1319 the disulfide bond formations of these residues with other Cys existed in the extracellular loops for the proper folding 1302:1421 We propose the disulfide bond formations of these residues with other Cys existed in the extracellular loops for the proper folding. 25690651 9 57 dep Cys 1212:1214 arg1 Ala 1242:1244 residue to Ala 1231:1244 residue to Ala 1231:1244 Substitution of Cys(18) or Cys(19) residue to Ala impaired Gi-mediated signaling via hGPR109A. 25690651 3 58 gly N-glycosylation 438:452 arg2 17 466:467 17 466:467 17 466:467 We found that human GPR109A (hGPR109A) has an N-glycosylation site at Asn(17) in the N-terminal atypical motif, Asn(17)-Cys(18)-Cys(19). 25690651 3 58 gly N-glycosylation 438:452 arg2 Asn 462:464 Asn 462:464 Asn(17) 462:468 We found that human GPR109A (hGPR109A) has an N-glycosylation site at Asn(17) in the N-terminal atypical motif, Asn(17)-Cys(18)-Cys(19). 25690651 3 58 gly N-glycosylation 438:452 arg2 site 454:457 an N-glycosylation site 435:457 an N-glycosylation site at Asn(17) 435:468 We found that human GPR109A (hGPR109A) has an N-glycosylation site at Asn(17) in the N-terminal atypical motif, Asn(17)-Cys(18)-Cys(19). 25690651 4 59 theme typical 591:597 arg1 sequence 599:606 the typical sequence 587:606 the typical sequence 587:606 Why does hGPR109A require the atypical motif, rather than the typical sequence? 25690651 2 60 theme Asn-X-Ser/Thr 331:343 arg1 motif 325:329 the N-glycosylation motif 305:329 the N-glycosylation motif Asn-X-Ser/Thr at their N-termini and/or extracellular loops 305:389 Thus, many GPCRs possess the N-glycosylation motif Asn-X-Ser/Thr at their N-termini and/or extracellular loops. 25690651 7 61 from Asn 1050:1052 arg1 N-glycosylated 1032:1045 N-glycosylated 1032:1045 N-glycosylated 1032:1045 This modification is required for the normal surface expression of hGPR109A, as evidenced by the reduced surface expression of the nonglycosylated mutants, hGPR109A/N17A, and the finding that hGPR109A/C19S and hGPR109A/C19T, which are N-glycosylated at Asn(17), exhibited expression similar to the wild-type receptor. 25690651 9 62 dep Ala 1242:1244 arg1 to 1239:1240 to 1239:1240 to 1239:1240 Substitution of Cys(18) or Cys(19) residue to Ala impaired Gi-mediated signaling via hGPR109A. 25690651 1 63 theme Asparagine-linked 142:158 arg1 N-glycosylation 175:189 N-glycosylation 175:189 N-glycosylation 175:189 Asparagine-linked glycosylation (N-glycosylation) is necessary for the proper folding of secreted and membrane proteins, including GPCRs. 25690651 1 63 theme Asparagine-linked 142:158 arg1 glycosylation 160:172 Asparagine-linked glycosylation 142:172 Asparagine-linked glycosylation (N-glycosylation) 142:190 Asparagine-linked glycosylation (N-glycosylation) is necessary for the proper folding of secreted and membrane proteins, including GPCRs. 25690651 7 64 gly nonglycosylated 928:942 arg1 mutants 944:950 the nonglycosylated mutants 924:950 the nonglycosylated mutants 924:950 This modification is required for the normal surface expression of hGPR109A, as evidenced by the reduced surface expression of the nonglycosylated mutants, hGPR109A/N17A, and the finding that hGPR109A/C19S and hGPR109A/C19T, which are N-glycosylated at Asn(17), exhibited expression similar to the wild-type receptor. 25690651 1 65 theme secreted 231:238 arg1 folding 220:226 the proper folding 209:226 the proper folding of secreted and membrane proteins, including GPCRs 209:277 Asparagine-linked glycosylation (N-glycosylation) is necessary for the proper folding of secreted and membrane proteins, including GPCRs. 25690651 10 66 theme proper 1408:1413 arg1 folding 1415:1421 the proper folding 1404:1421 the proper folding 1404:1421 We propose the disulfide bond formations of these residues with other Cys existed in the extracellular loops for the proper folding. 25690651 9 67 theme Cys 1223:1225 arg1 Substitution 1196:1207 Substitution 1196:1207 Substitution of Cys(18) or Cys(19) residue to Ala 1196:1244 Substitution of Cys(18) or Cys(19) residue to Ala impaired Gi-mediated signaling via hGPR109A. 25690651 9 68 theme Gi-mediated 1255:1265 arg1 signaling 1267:1275 Gi-mediated signaling 1255:1275 Gi-mediated signaling via hGPR109A 1255:1288 Substitution of Cys(18) or Cys(19) residue to Ala impaired Gi-mediated signaling via hGPR109A. 25690651 11 69 theme Asn 1480:1482 arg1 19 1500:1501 19 1500:1501 19 1500:1501 Together, these results suggest that the atypical motif Asn(17)-Cys(18)-Cys(19) is crucial for the normal surface trafficking and function of hGPR109A. 25690651 11 69 theme Asn 1480:1482 arg1 crucial 1507:1513 crucial 1507:1513 crucial 1507:1513 Together, these results suggest that the atypical motif Asn(17)-Cys(18)-Cys(19) is crucial for the normal surface trafficking and function of hGPR109A. 25690651 11 69 theme Asn 1480:1482 arg1 -Cys 1487:1490 the atypical motif Asn(17)-Cys(18)-Cys 1461:1498 the atypical motif Asn(17)-Cys(18)-Cys(19) 1461:1502 Together, these results suggest that the atypical motif Asn(17)-Cys(18)-Cys(19) is crucial for the normal surface trafficking and function of hGPR109A. 25690651 2 70 gly N-glycosylation 309:323 arg2 motif 325:329 the N-glycosylation motif 305:329 the N-glycosylation motif Asn-X-Ser/Thr at their N-termini and/or extracellular loops 305:389 Thus, many GPCRs possess the N-glycosylation motif Asn-X-Ser/Thr at their N-termini and/or extracellular loops. 25690651 0 71 from motif 29:33 arg1 GPR109A 58:64 human GPR109A 52:64 human GPR109A 52:64 The atypical N-glycosylation motif, Asn-Cys-Cys, in human GPR109A is required for normal cell surface expression and intracellular signaling. 25690651 10 72 theme other 1355:1359 arg1 Cys 1361:1363 other Cys 1355:1363 other Cys 1355:1363 We propose the disulfide bond formations of these residues with other Cys existed in the extracellular loops for the proper folding. 25690651 2 73 theme extracellular 371:383 arg1 loops 385:389 extracellular loops 371:389 extracellular loops 371:389 Thus, many GPCRs possess the N-glycosylation motif Asn-X-Ser/Thr at their N-termini and/or extracellular loops. 25690651 11 74 theme normal 1523:1528 arg1 trafficking 1538:1548 normal surface trafficking 1523:1548 normal surface trafficking 1523:1548 Together, these results suggest that the atypical motif Asn(17)-Cys(18)-Cys(19) is crucial for the normal surface trafficking and function of hGPR109A. 25690651 1 75 theme membrane 244:251 arg1 proteins 253:260 membrane proteins 244:260 membrane proteins 244:260 Asparagine-linked glycosylation (N-glycosylation) is necessary for the proper folding of secreted and membrane proteins, including GPCRs. 25690651 1 75 theme membrane 244:251 arg1 GPCRs 273:277 GPCRs 273:277 GPCRs 273:277 Asparagine-linked glycosylation (N-glycosylation) is necessary for the proper folding of secreted and membrane proteins, including GPCRs. 24336949 0 0 theme osteoblast 94:103 arg1 differentiation 105:119 osteoblast differentiation 94:119 osteoblast differentiation 94:119 Asparagine-linked glycosylation of bone morphogenetic protein-2 is required for secretion and osteoblast differentiation. 24336949 4 1 theme initial 467:473 arg1 processing 482:491 initial glycan processing 467:491 initial glycan processing 467:491 Blocking the addition of NLGs or inhibiting initial glycan processing prevented the secretion of BMP-2. 24336949 5 2 theme BMP-2 737:741 arg1 mutants 743:749 the BMP-2 mutants 733:749 the BMP-2 mutants 733:749 To identify the specific glycosylation sites, we abolished potential sites of N-linked glycosylation (Asn-Xaa-Ser/Thr) in BMP-2 by mutating the Asn residues to Gln individually or in combination, expressed the BMP-2 mutants in Chinese hamster ovary (CHO) and human embryonic kidney 293T (HEK293T) cells and determined their glycosylation state by using peptide:N-glycosidase F and endoglycosidase H digestion. 24336949 5 3 theme Asn 671:673 arg1 residues 675:682 the Asn residues 667:682 the Asn residues 667:682 To identify the specific glycosylation sites, we abolished potential sites of N-linked glycosylation (Asn-Xaa-Ser/Thr) in BMP-2 by mutating the Asn residues to Gln individually or in combination, expressed the BMP-2 mutants in Chinese hamster ovary (CHO) and human embryonic kidney 293T (HEK293T) cells and determined their glycosylation state by using peptide:N-glycosidase F and endoglycosidase H digestion. 24336949 1 4 theme glycosylated 162:173 arg1 protein-2 141:149 Bone morphogenetic protein-2 122:149 Bone morphogenetic protein-2 (BMP-2) 122:157 Bone morphogenetic protein-2 (BMP-2), a glycosylated protein, has been demonstrated to play a key role in osteoblast differentiation. 24336949 1 4 theme glycosylated 162:173 arg1 protein 175:181 a glycosylated protein 160:181 a glycosylated protein 160:181 Bone morphogenetic protein-2 (BMP-2), a glycosylated protein, has been demonstrated to play a key role in osteoblast differentiation. 24336949 5 5 gly glycosylation 552:564 arg2 sites 566:570 the specific glycosylation sites 539:570 the specific glycosylation sites 539:570 To identify the specific glycosylation sites, we abolished potential sites of N-linked glycosylation (Asn-Xaa-Ser/Thr) in BMP-2 by mutating the Asn residues to Gln individually or in combination, expressed the BMP-2 mutants in Chinese hamster ovary (CHO) and human embryonic kidney 293T (HEK293T) cells and determined their glycosylation state by using peptide:N-glycosidase F and endoglycosidase H digestion. 24336949 8 6 theme CHO 1226:1228 arg1 cells 1230:1234 CHO cells 1226:1234 CHO cells 1226:1234 Overexpression of the BMP-2 mutant N135Q elicited endoplasmic reticulum (ER) stress and retention within the ER in CHO cells, indicating that N-glycosylation is required for folding of human BMP-2. 24336949 7 7 theme N135 1052:1055 arg1 mutation 1040:1047 mutation 1040:1047 mutation of N135 (N135Q) 1040:1063 Elimination of N-glycosylation by mutation of N135 (N135Q) abolished the BMP-2 secretion from CHO cells. 24336949 5 8 theme glycosylation 851:863 arg1 state 865:869 their glycosylation state 845:869 their glycosylation state 845:869 To identify the specific glycosylation sites, we abolished potential sites of N-linked glycosylation (Asn-Xaa-Ser/Thr) in BMP-2 by mutating the Asn residues to Gln individually or in combination, expressed the BMP-2 mutants in Chinese hamster ovary (CHO) and human embryonic kidney 293T (HEK293T) cells and determined their glycosylation state by using peptide:N-glycosidase F and endoglycosidase H digestion. 24336949 8 9 theme endoplasmic 1161:1171 arg1 ER 1184:1185 ER 1184:1185 ER 1184:1185 Overexpression of the BMP-2 mutant N135Q elicited endoplasmic reticulum (ER) stress and retention within the ER in CHO cells, indicating that N-glycosylation is required for folding of human BMP-2. 24336949 8 9 theme endoplasmic 1161:1171 arg1 reticulum 1173:1181 endoplasmic reticulum 1161:1181 endoplasmic reticulum (ER) 1161:1186 Overexpression of the BMP-2 mutant N135Q elicited endoplasmic reticulum (ER) stress and retention within the ER in CHO cells, indicating that N-glycosylation is required for folding of human BMP-2. 24336949 10 10 theme role 1511:1514 arg1 evidence 1486:1493 further evidence 1478:1493 further evidence of the critical role that individual NLG may play an important role in determining BMP-2 folding, secretion and function 1478:1614 Taken together, these data provide further evidence of the critical role that individual NLG may play an important role in determining BMP-2 folding, secretion and function. 24336949 6 11 from NLG 978:980 arg1 N338 1000:1003 N338 1000:1003 N338 1000:1003 We found that human BMP-2 contains three NLG on N135, N200 and N338. 24336949 6 11 from NLG 978:980 arg1 N200 991:994 N200 991:994 N200 991:994 We found that human BMP-2 contains three NLG on N135, N200 and N338. 24336949 6 11 from NLG 978:980 arg1 N135 985:988 N135 985:988 N135 985:988 We found that human BMP-2 contains three NLG on N135, N200 and N338. 24336949 2 12 theme glycosylation 285:297 arg1 function 269:276 the function 265:276 the function of its glycosylation 265:297 However, the function of its glycosylation is incompletely understood. 24336949 9 13 from N135 1360:1363 arg1 glycosylation 1343:1355 glycosylation 1343:1355 glycosylation at N135 1343:1363 Furthermore, we demonstrated that glycosylation at N135 was necessary for BMP-2-induced osteoblast differentiation in MC3T3-E1 cells. 24336949 10 14 theme critical 1502:1509 arg1 role 1511:1514 the critical role 1498:1514 the critical role that individual NLG may play an important role in determining BMP-2 folding, secretion and function 1498:1614 Taken together, these data provide further evidence of the critical role that individual NLG may play an important role in determining BMP-2 folding, secretion and function. 24336949 4 15 theme NLGs 448:451 arg1 addition 436:443 the addition 432:443 the addition of NLGs 432:451 Blocking the addition of NLGs or inhibiting initial glycan processing prevented the secretion of BMP-2. 24336949 6 16 contain contains 963:970 arg2 NLG 978:980 three NLG 972:980 three NLG on N135, N200 and N338 972:1003 We found that human BMP-2 contains three NLG on N135, N200 and N338. 24336949 6 16 contain contains 963:970 arg1 BMP-2 957:961 human BMP-2 951:961 human BMP-2 951:961 We found that human BMP-2 contains three NLG on N135, N200 and N338. 24336949 5 17 theme potential 586:594 arg1 glycosylation 614:626 N-linked glycosylation 605:626 N-linked glycosylation (Asn-Xaa-Ser/Thr) 605:644 To identify the specific glycosylation sites, we abolished potential sites of N-linked glycosylation (Asn-Xaa-Ser/Thr) in BMP-2 by mutating the Asn residues to Gln individually or in combination, expressed the BMP-2 mutants in Chinese hamster ovary (CHO) and human embryonic kidney 293T (HEK293T) cells and determined their glycosylation state by using peptide:N-glycosidase F and endoglycosidase H digestion. 24336949 5 17 theme potential 586:594 arg1 sites 596:600 potential sites 586:600 potential sites of N-linked glycosylation (Asn-Xaa-Ser/Thr) in BMP-2 586:653 To identify the specific glycosylation sites, we abolished potential sites of N-linked glycosylation (Asn-Xaa-Ser/Thr) in BMP-2 by mutating the Asn residues to Gln individually or in combination, expressed the BMP-2 mutants in Chinese hamster ovary (CHO) and human embryonic kidney 293T (HEK293T) cells and determined their glycosylation state by using peptide:N-glycosidase F and endoglycosidase H digestion. 24336949 5 18 theme H 924:924 arg1 digestion 926:934 peptide:N-glycosidase F and endoglycosidase H digestion 880:934 digestion 926:934 To identify the specific glycosylation sites, we abolished potential sites of N-linked glycosylation (Asn-Xaa-Ser/Thr) in BMP-2 by mutating the Asn residues to Gln individually or in combination, expressed the BMP-2 mutants in Chinese hamster ovary (CHO) and human embryonic kidney 293T (HEK293T) cells and determined their glycosylation state by using peptide:N-glycosidase F and endoglycosidase H digestion. 24336949 0 19 link Asparagine-linked 0:16 arg1 glycosylation 18:30 Asparagine-linked glycosylation 0:30 Asparagine-linked glycosylation of bone morphogenetic protein-2 0:62 Asparagine-linked glycosylation of bone morphogenetic protein-2 is required for secretion and osteoblast differentiation. 24336949 10 20 theme BMP-2 1578:1582 arg1 folding 1584:1590 BMP-2 folding 1578:1590 BMP-2 folding 1578:1590 Taken together, these data provide further evidence of the critical role that individual NLG may play an important role in determining BMP-2 folding, secretion and function. 24336949 5 21 theme N-linked 605:612 arg1 glycosylation 614:626 N-linked glycosylation 605:626 N-linked glycosylation (Asn-Xaa-Ser/Thr) 605:644 To identify the specific glycosylation sites, we abolished potential sites of N-linked glycosylation (Asn-Xaa-Ser/Thr) in BMP-2 by mutating the Asn residues to Gln individually or in combination, expressed the BMP-2 mutants in Chinese hamster ovary (CHO) and human embryonic kidney 293T (HEK293T) cells and determined their glycosylation state by using peptide:N-glycosidase F and endoglycosidase H digestion. 24336949 5 21 theme N-linked 605:612 arg1 Asn-Xaa-Ser/Thr 629:643 Asn-Xaa-Ser/Thr 629:643 Asn-Xaa-Ser/Thr 629:643 To identify the specific glycosylation sites, we abolished potential sites of N-linked glycosylation (Asn-Xaa-Ser/Thr) in BMP-2 by mutating the Asn residues to Gln individually or in combination, expressed the BMP-2 mutants in Chinese hamster ovary (CHO) and human embryonic kidney 293T (HEK293T) cells and determined their glycosylation state by using peptide:N-glycosidase F and endoglycosidase H digestion. 24336949 5 22 theme specific 543:550 arg1 sites 566:570 the specific glycosylation sites 539:570 the specific glycosylation sites 539:570 To identify the specific glycosylation sites, we abolished potential sites of N-linked glycosylation (Asn-Xaa-Ser/Thr) in BMP-2 by mutating the Asn residues to Gln individually or in combination, expressed the BMP-2 mutants in Chinese hamster ovary (CHO) and human embryonic kidney 293T (HEK293T) cells and determined their glycosylation state by using peptide:N-glycosidase F and endoglycosidase H digestion. 24336949 3 23 theme BMP-2 416:420 arg1 secretion 403:411 the secretion 399:411 the secretion of BMP-2 399:420 In this study, we examined the role that N-linked glycans (NLG) play in the secretion of BMP-2. 24336949 7 24 theme CHO 1100:1102 arg1 cells 1104:1108 CHO cells 1100:1108 CHO cells 1100:1108 Elimination of N-glycosylation by mutation of N135 (N135Q) abolished the BMP-2 secretion from CHO cells. 24336949 7 25 from cells 1104:1108 arg1 secretion 1085:1093 the BMP-2 secretion 1075:1093 the BMP-2 secretion from CHO cells 1075:1108 Elimination of N-glycosylation by mutation of N135 (N135Q) abolished the BMP-2 secretion from CHO cells. 24336949 5 26 theme glycosylation 614:626 arg1 glycosylation 614:626 N-linked glycosylation 605:626 N-linked glycosylation (Asn-Xaa-Ser/Thr) 605:644 To identify the specific glycosylation sites, we abolished potential sites of N-linked glycosylation (Asn-Xaa-Ser/Thr) in BMP-2 by mutating the Asn residues to Gln individually or in combination, expressed the BMP-2 mutants in Chinese hamster ovary (CHO) and human embryonic kidney 293T (HEK293T) cells and determined their glycosylation state by using peptide:N-glycosidase F and endoglycosidase H digestion. 24336949 5 26 theme glycosylation 614:626 arg1 sites 596:600 potential sites 586:600 potential sites of N-linked glycosylation (Asn-Xaa-Ser/Thr) in BMP-2 586:653 To identify the specific glycosylation sites, we abolished potential sites of N-linked glycosylation (Asn-Xaa-Ser/Thr) in BMP-2 by mutating the Asn residues to Gln individually or in combination, expressed the BMP-2 mutants in Chinese hamster ovary (CHO) and human embryonic kidney 293T (HEK293T) cells and determined their glycosylation state by using peptide:N-glycosidase F and endoglycosidase H digestion. 24336949 5 27 theme glycosylation 552:564 arg1 sites 566:570 the specific glycosylation sites 539:570 the specific glycosylation sites 539:570 To identify the specific glycosylation sites, we abolished potential sites of N-linked glycosylation (Asn-Xaa-Ser/Thr) in BMP-2 by mutating the Asn residues to Gln individually or in combination, expressed the BMP-2 mutants in Chinese hamster ovary (CHO) and human embryonic kidney 293T (HEK293T) cells and determined their glycosylation state by using peptide:N-glycosidase F and endoglycosidase H digestion. 24336949 10 28 theme individual 1521:1530 arg1 NLG 1532:1534 individual NLG 1521:1534 individual NLG 1521:1534 Taken together, these data provide further evidence of the critical role that individual NLG may play an important role in determining BMP-2 folding, secretion and function. 24336949 9 29 theme BMP-2-induced 1383:1395 arg1 differentiation 1408:1422 BMP-2-induced osteoblast differentiation 1383:1422 BMP-2-induced osteoblast differentiation in MC3T3-E1 cells 1383:1440 Furthermore, we demonstrated that glycosylation at N135 was necessary for BMP-2-induced osteoblast differentiation in MC3T3-E1 cells. 24336949 0 30 theme Asparagine-linked 0:16 arg1 glycosylation 18:30 Asparagine-linked glycosylation 0:30 Asparagine-linked glycosylation of bone morphogenetic protein-2 0:62 Asparagine-linked glycosylation of bone morphogenetic protein-2 is required for secretion and osteoblast differentiation. 24336949 7 31 theme BMP-2 1079:1083 arg1 secretion 1085:1093 the BMP-2 secretion 1075:1093 the BMP-2 secretion from CHO cells 1075:1108 Elimination of N-glycosylation by mutation of N135 (N135Q) abolished the BMP-2 secretion from CHO cells. 24336949 7 32 theme N-glycosylation 1021:1035 arg1 Elimination 1006:1016 Elimination 1006:1016 Elimination of N-glycosylation by mutation of N135 (N135Q) 1006:1063 Elimination of N-glycosylation by mutation of N135 (N135Q) abolished the BMP-2 secretion from CHO cells. 24336949 5 33 theme N-glycosidase 888:900 arg1 F 902:902 peptide:N-glycosidase F and endoglycosidase H digestion 880:934 F 902:902 To identify the specific glycosylation sites, we abolished potential sites of N-linked glycosylation (Asn-Xaa-Ser/Thr) in BMP-2 by mutating the Asn residues to Gln individually or in combination, expressed the BMP-2 mutants in Chinese hamster ovary (CHO) and human embryonic kidney 293T (HEK293T) cells and determined their glycosylation state by using peptide:N-glycosidase F and endoglycosidase H digestion. 24336949 6 34 theme human 951:955 arg1 BMP-2 957:961 human BMP-2 951:961 human BMP-2 951:961 We found that human BMP-2 contains three NLG on N135, N200 and N338. 24336949 5 35 link N-linked 605:612 arg1 glycosylation 614:626 N-linked glycosylation 605:626 N-linked glycosylation (Asn-Xaa-Ser/Thr) 605:644 To identify the specific glycosylation sites, we abolished potential sites of N-linked glycosylation (Asn-Xaa-Ser/Thr) in BMP-2 by mutating the Asn residues to Gln individually or in combination, expressed the BMP-2 mutants in Chinese hamster ovary (CHO) and human embryonic kidney 293T (HEK293T) cells and determined their glycosylation state by using peptide:N-glycosidase F and endoglycosidase H digestion. 24336949 5 35 link N-linked 605:612 arg1 Asn-Xaa-Ser/Thr 629:643 Asn-Xaa-Ser/Thr 629:643 Asn-Xaa-Ser/Thr 629:643 To identify the specific glycosylation sites, we abolished potential sites of N-linked glycosylation (Asn-Xaa-Ser/Thr) in BMP-2 by mutating the Asn residues to Gln individually or in combination, expressed the BMP-2 mutants in Chinese hamster ovary (CHO) and human embryonic kidney 293T (HEK293T) cells and determined their glycosylation state by using peptide:N-glycosidase F and endoglycosidase H digestion. 24336949 0 36 theme bone 35:38 arg1 protein-2 54:62 bone morphogenetic protein-2 35:62 bone morphogenetic protein-2 35:62 Asparagine-linked glycosylation of bone morphogenetic protein-2 is required for secretion and osteoblast differentiation. 24336949 8 37 gly N-glycosylation 1253:1267 arg1 BMP-2 1302:1306 human BMP-2 1296:1306 human BMP-2 1296:1306 Overexpression of the BMP-2 mutant N135Q elicited endoplasmic reticulum (ER) stress and retention within the ER in CHO cells, indicating that N-glycosylation is required for folding of human BMP-2. 24336949 1 38 theme Bone 122:125 arg1 BMP-2 152:156 BMP-2 152:156 BMP-2 152:156 Bone morphogenetic protein-2 (BMP-2), a glycosylated protein, has been demonstrated to play a key role in osteoblast differentiation. 24336949 1 38 theme Bone 122:125 arg1 protein-2 141:149 Bone morphogenetic protein-2 122:149 Bone morphogenetic protein-2 (BMP-2) 122:157 Bone morphogenetic protein-2 (BMP-2), a glycosylated protein, has been demonstrated to play a key role in osteoblast differentiation. 24336949 1 38 theme Bone 122:125 arg1 protein 175:181 a glycosylated protein 160:181 a glycosylated protein 160:181 Bone morphogenetic protein-2 (BMP-2), a glycosylated protein, has been demonstrated to play a key role in osteoblast differentiation. 24336949 5 39 theme endoglycosidase 908:922 arg1 digestion 926:934 peptide:N-glycosidase F and endoglycosidase H digestion 880:934 digestion 926:934 To identify the specific glycosylation sites, we abolished potential sites of N-linked glycosylation (Asn-Xaa-Ser/Thr) in BMP-2 by mutating the Asn residues to Gln individually or in combination, expressed the BMP-2 mutants in Chinese hamster ovary (CHO) and human embryonic kidney 293T (HEK293T) cells and determined their glycosylation state by using peptide:N-glycosidase F and endoglycosidase H digestion. 24336949 3 40 theme N-linked 368:375 arg1 glycans 377:383 N-linked glycans 368:383 N-linked glycans (NLG) 368:389 In this study, we examined the role that N-linked glycans (NLG) play in the secretion of BMP-2. 24336949 3 40 theme N-linked 368:375 arg1 NLG 386:388 NLG 386:388 NLG 386:388 In this study, we examined the role that N-linked glycans (NLG) play in the secretion of BMP-2. 24336949 1 41 theme morphogenetic 127:139 arg1 BMP-2 152:156 BMP-2 152:156 BMP-2 152:156 Bone morphogenetic protein-2 (BMP-2), a glycosylated protein, has been demonstrated to play a key role in osteoblast differentiation. 24336949 1 41 theme morphogenetic 127:139 arg1 protein-2 141:149 Bone morphogenetic protein-2 122:149 Bone morphogenetic protein-2 (BMP-2) 122:157 Bone morphogenetic protein-2 (BMP-2), a glycosylated protein, has been demonstrated to play a key role in osteoblast differentiation. 24336949 1 41 theme morphogenetic 127:139 arg1 protein 175:181 a glycosylated protein 160:181 a glycosylated protein 160:181 Bone morphogenetic protein-2 (BMP-2), a glycosylated protein, has been demonstrated to play a key role in osteoblast differentiation. 24336949 5 42 theme embryonic 792:800 arg1 cells 824:828 human embryonic kidney 293T (HEK293T) cells 786:828 human embryonic kidney 293T (HEK293T) cells 786:828 To identify the specific glycosylation sites, we abolished potential sites of N-linked glycosylation (Asn-Xaa-Ser/Thr) in BMP-2 by mutating the Asn residues to Gln individually or in combination, expressed the BMP-2 mutants in Chinese hamster ovary (CHO) and human embryonic kidney 293T (HEK293T) cells and determined their glycosylation state by using peptide:N-glycosidase F and endoglycosidase H digestion. 24336949 0 43 theme protein-2 54:62 arg1 glycosylation 18:30 Asparagine-linked glycosylation 0:30 Asparagine-linked glycosylation of bone morphogenetic protein-2 0:62 Asparagine-linked glycosylation of bone morphogenetic protein-2 is required for secretion and osteoblast differentiation. 24336949 9 44 theme MC3T3-E1 1427:1434 arg1 cells 1436:1440 MC3T3-E1 cells 1427:1440 MC3T3-E1 cells 1427:1440 Furthermore, we demonstrated that glycosylation at N135 was necessary for BMP-2-induced osteoblast differentiation in MC3T3-E1 cells. 24336949 10 45 dep role 1511:1514 arg1 play 1540:1543 play 1540:1543 may play an important role in determining BMP-2 folding, secretion and function 1536:1614 Taken together, these data provide further evidence of the critical role that individual NLG may play an important role in determining BMP-2 folding, secretion and function. 24336949 9 46 theme osteoblast 1397:1406 arg1 differentiation 1408:1422 BMP-2-induced osteoblast differentiation 1383:1422 BMP-2-induced osteoblast differentiation in MC3T3-E1 cells 1383:1440 Furthermore, we demonstrated that glycosylation at N135 was necessary for BMP-2-induced osteoblast differentiation in MC3T3-E1 cells. 24336949 5 47 theme kidney 802:807 arg1 cells 824:828 human embryonic kidney 293T (HEK293T) cells 786:828 human embryonic kidney 293T (HEK293T) cells 786:828 To identify the specific glycosylation sites, we abolished potential sites of N-linked glycosylation (Asn-Xaa-Ser/Thr) in BMP-2 by mutating the Asn residues to Gln individually or in combination, expressed the BMP-2 mutants in Chinese hamster ovary (CHO) and human embryonic kidney 293T (HEK293T) cells and determined their glycosylation state by using peptide:N-glycosidase F and endoglycosidase H digestion. 24336949 0 48 theme morphogenetic 40:52 arg1 protein-2 54:62 bone morphogenetic protein-2 35:62 bone morphogenetic protein-2 35:62 Asparagine-linked glycosylation of bone morphogenetic protein-2 is required for secretion and osteoblast differentiation. 24336949 5 49 theme Chinese 754:760 arg1 CHO 777:779 CHO 777:779 CHO 777:779 To identify the specific glycosylation sites, we abolished potential sites of N-linked glycosylation (Asn-Xaa-Ser/Thr) in BMP-2 by mutating the Asn residues to Gln individually or in combination, expressed the BMP-2 mutants in Chinese hamster ovary (CHO) and human embryonic kidney 293T (HEK293T) cells and determined their glycosylation state by using peptide:N-glycosidase F and endoglycosidase H digestion. 24336949 5 49 theme Chinese 754:760 arg1 ovary 770:774 Chinese hamster ovary 754:774 Chinese hamster ovary (CHO) 754:780 To identify the specific glycosylation sites, we abolished potential sites of N-linked glycosylation (Asn-Xaa-Ser/Thr) in BMP-2 by mutating the Asn residues to Gln individually or in combination, expressed the BMP-2 mutants in Chinese hamster ovary (CHO) and human embryonic kidney 293T (HEK293T) cells and determined their glycosylation state by using peptide:N-glycosidase F and endoglycosidase H digestion. 24336949 0 50 gly glycosylation 18:30 arg1 protein-2 54:62 bone morphogenetic protein-2 35:62 bone morphogenetic protein-2 35:62 Asparagine-linked glycosylation of bone morphogenetic protein-2 is required for secretion and osteoblast differentiation. 24336949 0 50 gly glycosylation 18:30 arg1 osteoblast 94:103 osteoblast differentiation 94:119 osteoblast differentiation 94:119 Asparagine-linked glycosylation of bone morphogenetic protein-2 is required for secretion and osteoblast differentiation. 24336949 5 51 theme 293T 809:812 arg1 cells 824:828 human embryonic kidney 293T (HEK293T) cells 786:828 human embryonic kidney 293T (HEK293T) cells 786:828 To identify the specific glycosylation sites, we abolished potential sites of N-linked glycosylation (Asn-Xaa-Ser/Thr) in BMP-2 by mutating the Asn residues to Gln individually or in combination, expressed the BMP-2 mutants in Chinese hamster ovary (CHO) and human embryonic kidney 293T (HEK293T) cells and determined their glycosylation state by using peptide:N-glycosidase F and endoglycosidase H digestion. 24336949 1 52 theme key 216:218 arg1 role 220:223 a key role 214:223 a key role 214:223 Bone morphogenetic protein-2 (BMP-2), a glycosylated protein, has been demonstrated to play a key role in osteoblast differentiation. 24336949 5 53 theme hamster 762:768 arg1 CHO 777:779 CHO 777:779 CHO 777:779 To identify the specific glycosylation sites, we abolished potential sites of N-linked glycosylation (Asn-Xaa-Ser/Thr) in BMP-2 by mutating the Asn residues to Gln individually or in combination, expressed the BMP-2 mutants in Chinese hamster ovary (CHO) and human embryonic kidney 293T (HEK293T) cells and determined their glycosylation state by using peptide:N-glycosidase F and endoglycosidase H digestion. 24336949 5 53 theme hamster 762:768 arg1 ovary 770:774 Chinese hamster ovary 754:774 Chinese hamster ovary (CHO) 754:780 To identify the specific glycosylation sites, we abolished potential sites of N-linked glycosylation (Asn-Xaa-Ser/Thr) in BMP-2 by mutating the Asn residues to Gln individually or in combination, expressed the BMP-2 mutants in Chinese hamster ovary (CHO) and human embryonic kidney 293T (HEK293T) cells and determined their glycosylation state by using peptide:N-glycosidase F and endoglycosidase H digestion. 24336949 8 54 theme BMP-2 1133:1137 arg1 N135Q 1146:1150 the BMP-2 mutant N135Q 1129:1150 the BMP-2 mutant N135Q 1129:1150 Overexpression of the BMP-2 mutant N135Q elicited endoplasmic reticulum (ER) stress and retention within the ER in CHO cells, indicating that N-glycosylation is required for folding of human BMP-2. 24336949 10 55 theme further 1478:1484 arg1 evidence 1486:1493 further evidence 1478:1493 further evidence of the critical role that individual NLG may play an important role in determining BMP-2 folding, secretion and function 1478:1614 Taken together, these data provide further evidence of the critical role that individual NLG may play an important role in determining BMP-2 folding, secretion and function. 24336949 9 56 from differentiation 1408:1422 arg1 cells 1436:1440 MC3T3-E1 cells 1427:1440 MC3T3-E1 cells 1427:1440 Furthermore, we demonstrated that glycosylation at N135 was necessary for BMP-2-induced osteoblast differentiation in MC3T3-E1 cells. 24336949 8 57 theme N135Q 1146:1150 arg1 Overexpression 1111:1124 Overexpression 1111:1124 Overexpression of the BMP-2 mutant N135Q 1111:1150 Overexpression of the BMP-2 mutant N135Q elicited endoplasmic reticulum (ER) stress and retention within the ER in CHO cells, indicating that N-glycosylation is required for folding of human BMP-2. 24336949 4 58 theme BMP-2 520:524 arg1 secretion 507:515 the secretion 503:515 the secretion of BMP-2 503:524 Blocking the addition of NLGs or inhibiting initial glycan processing prevented the secretion of BMP-2. 24336949 8 59 theme mutant 1139:1144 arg1 N135Q 1146:1150 the BMP-2 mutant N135Q 1129:1150 the BMP-2 mutant N135Q 1129:1150 Overexpression of the BMP-2 mutant N135Q elicited endoplasmic reticulum (ER) stress and retention within the ER in CHO cells, indicating that N-glycosylation is required for folding of human BMP-2. 24336949 8 60 theme BMP-2 1302:1306 arg1 folding 1285:1291 folding 1285:1291 folding of human BMP-2 1285:1306 Overexpression of the BMP-2 mutant N135Q elicited endoplasmic reticulum (ER) stress and retention within the ER in CHO cells, indicating that N-glycosylation is required for folding of human BMP-2. 24336949 8 61 theme human 1296:1300 arg1 BMP-2 1302:1306 human BMP-2 1296:1306 human BMP-2 1296:1306 Overexpression of the BMP-2 mutant N135Q elicited endoplasmic reticulum (ER) stress and retention within the ER in CHO cells, indicating that N-glycosylation is required for folding of human BMP-2. 24336949 1 62 gly glycosylated 162:173 arg1 protein-2 141:149 Bone morphogenetic protein-2 122:149 Bone morphogenetic protein-2 (BMP-2) 122:157 Bone morphogenetic protein-2 (BMP-2), a glycosylated protein, has been demonstrated to play a key role in osteoblast differentiation. 24336949 1 62 gly glycosylated 162:173 arg1 protein 175:181 a glycosylated protein 160:181 a glycosylated protein 160:181 Bone morphogenetic protein-2 (BMP-2), a glycosylated protein, has been demonstrated to play a key role in osteoblast differentiation. 24336949 3 63 link N-linked 368:375 arg1 glycans 377:383 N-linked glycans 368:383 N-linked glycans (NLG) 368:389 In this study, we examined the role that N-linked glycans (NLG) play in the secretion of BMP-2. 24336949 3 63 link N-linked 368:375 arg1 NLG 386:388 NLG 386:388 NLG 386:388 In this study, we examined the role that N-linked glycans (NLG) play in the secretion of BMP-2. 24336949 5 64 theme peptide 880:886 arg1 F 902:902 peptide:N-glycosidase F and endoglycosidase H digestion 880:934 F 902:902 To identify the specific glycosylation sites, we abolished potential sites of N-linked glycosylation (Asn-Xaa-Ser/Thr) in BMP-2 by mutating the Asn residues to Gln individually or in combination, expressed the BMP-2 mutants in Chinese hamster ovary (CHO) and human embryonic kidney 293T (HEK293T) cells and determined their glycosylation state by using peptide:N-glycosidase F and endoglycosidase H digestion. 24336949 5 65 gly glycosylation 614:626 arg2 sites 596:600 potential sites 586:600 potential sites of N-linked glycosylation (Asn-Xaa-Ser/Thr) in BMP-2 586:653 To identify the specific glycosylation sites, we abolished potential sites of N-linked glycosylation (Asn-Xaa-Ser/Thr) in BMP-2 by mutating the Asn residues to Gln individually or in combination, expressed the BMP-2 mutants in Chinese hamster ovary (CHO) and human embryonic kidney 293T (HEK293T) cells and determined their glycosylation state by using peptide:N-glycosidase F and endoglycosidase H digestion. 24336949 5 65 gly glycosylation 614:626 arg2 glycosylation 614:626 N-linked glycosylation 605:626 N-linked glycosylation (Asn-Xaa-Ser/Thr) 605:644 To identify the specific glycosylation sites, we abolished potential sites of N-linked glycosylation (Asn-Xaa-Ser/Thr) in BMP-2 by mutating the Asn residues to Gln individually or in combination, expressed the BMP-2 mutants in Chinese hamster ovary (CHO) and human embryonic kidney 293T (HEK293T) cells and determined their glycosylation state by using peptide:N-glycosidase F and endoglycosidase H digestion. 24336949 5 65 gly glycosylation 614:626 arg1 BMP-2 649:653 BMP-2 649:653 BMP-2 649:653 To identify the specific glycosylation sites, we abolished potential sites of N-linked glycosylation (Asn-Xaa-Ser/Thr) in BMP-2 by mutating the Asn residues to Gln individually or in combination, expressed the BMP-2 mutants in Chinese hamster ovary (CHO) and human embryonic kidney 293T (HEK293T) cells and determined their glycosylation state by using peptide:N-glycosidase F and endoglycosidase H digestion. 24336949 9 66 gly glycosylation 1343:1355 arg1 N135 1360:1363 N135 1360:1363 N135 1360:1363 Furthermore, we demonstrated that glycosylation at N135 was necessary for BMP-2-induced osteoblast differentiation in MC3T3-E1 cells. 24336949 9 66 gly glycosylation 1343:1355 arg2 N135 1360:1363 N135 1360:1363 N135 1360:1363 Furthermore, we demonstrated that glycosylation at N135 was necessary for BMP-2-induced osteoblast differentiation in MC3T3-E1 cells. 24336949 5 67 theme human 786:790 arg1 cells 824:828 human embryonic kidney 293T (HEK293T) cells 786:828 human embryonic kidney 293T (HEK293T) cells 786:828 To identify the specific glycosylation sites, we abolished potential sites of N-linked glycosylation (Asn-Xaa-Ser/Thr) in BMP-2 by mutating the Asn residues to Gln individually or in combination, expressed the BMP-2 mutants in Chinese hamster ovary (CHO) and human embryonic kidney 293T (HEK293T) cells and determined their glycosylation state by using peptide:N-glycosidase F and endoglycosidase H digestion. 24336949 5 68 theme HEK293T 815:821 arg1 cells 824:828 human embryonic kidney 293T (HEK293T) cells 786:828 human embryonic kidney 293T (HEK293T) cells 786:828 To identify the specific glycosylation sites, we abolished potential sites of N-linked glycosylation (Asn-Xaa-Ser/Thr) in BMP-2 by mutating the Asn residues to Gln individually or in combination, expressed the BMP-2 mutants in Chinese hamster ovary (CHO) and human embryonic kidney 293T (HEK293T) cells and determined their glycosylation state by using peptide:N-glycosidase F and endoglycosidase H digestion. 24336949 1 69 theme osteoblast 228:237 arg1 differentiation 239:253 osteoblast differentiation 228:253 osteoblast differentiation 228:253 Bone morphogenetic protein-2 (BMP-2), a glycosylated protein, has been demonstrated to play a key role in osteoblast differentiation. 24336949 8 70 dep reticulum 1173:1181 arg1 stress 1188:1193 stress 1188:1193 stress 1188:1193 Overexpression of the BMP-2 mutant N135Q elicited endoplasmic reticulum (ER) stress and retention within the ER in CHO cells, indicating that N-glycosylation is required for folding of human BMP-2. 24336949 4 71 theme glycan 475:480 arg1 processing 482:491 initial glycan processing 467:491 initial glycan processing 467:491 Blocking the addition of NLGs or inhibiting initial glycan processing prevented the secretion of BMP-2. 24336949 5 72 from sites 596:600 arg1 BMP-2 649:653 BMP-2 649:653 BMP-2 649:653 To identify the specific glycosylation sites, we abolished potential sites of N-linked glycosylation (Asn-Xaa-Ser/Thr) in BMP-2 by mutating the Asn residues to Gln individually or in combination, expressed the BMP-2 mutants in Chinese hamster ovary (CHO) and human embryonic kidney 293T (HEK293T) cells and determined their glycosylation state by using peptide:N-glycosidase F and endoglycosidase H digestion. 24336949 10 73 theme important 1548:1556 arg1 role 1558:1561 an important role 1545:1561 an important role 1545:1561 Taken together, these data provide further evidence of the critical role that individual NLG may play an important role in determining BMP-2 folding, secretion and function. 27381217 0 0 theme virus 160:164 arg1 antigenicity 129:140 the antigenicity 125:140 the antigenicity of the human H7N9 virus 125:164 The S128N mutation combined with an additional potential N-linked glycosylation site at residue 133 in hemagglutinin affects the antigenicity of the human H7N9 virus. 27381217 0 1 link N-linked 57:64 arg1 site 80:83 an additional potential N-linked glycosylation site 33:83 an additional potential N-linked glycosylation site at residue 133 in hemagglutinin 33:115 The S128N mutation combined with an additional potential N-linked glycosylation site at residue 133 in hemagglutinin affects the antigenicity of the human H7N9 virus. 27381217 0 2 from site 80:83 arg1 hemagglutinin 103:115 hemagglutinin 103:115 hemagglutinin 103:115 The S128N mutation combined with an additional potential N-linked glycosylation site at residue 133 in hemagglutinin affects the antigenicity of the human H7N9 virus. 27381217 0 3 theme S128N 4:8 arg1 mutation 10:17 The S128N mutation 0:17 The S128N mutation combined with an additional potential N-linked glycosylation site at residue 133 in hemagglutinin 0:115 The S128N mutation combined with an additional potential N-linked glycosylation site at residue 133 in hemagglutinin affects the antigenicity of the human H7N9 virus. 27381217 0 4 theme H7N9 155:158 arg1 virus 160:164 the human H7N9 virus 145:164 the human H7N9 virus 145:164 The S128N mutation combined with an additional potential N-linked glycosylation site at residue 133 in hemagglutinin affects the antigenicity of the human H7N9 virus. 27381217 0 5 theme glycosylation 66:78 arg1 site 80:83 an additional potential N-linked glycosylation site 33:83 an additional potential N-linked glycosylation site at residue 133 in hemagglutinin 33:115 The S128N mutation combined with an additional potential N-linked glycosylation site at residue 133 in hemagglutinin affects the antigenicity of the human H7N9 virus. 27381217 0 6 from residue 88:94 arg1 site 80:83 an additional potential N-linked glycosylation site 33:83 an additional potential N-linked glycosylation site at residue 133 in hemagglutinin 33:115 The S128N mutation combined with an additional potential N-linked glycosylation site at residue 133 in hemagglutinin affects the antigenicity of the human H7N9 virus. 27381217 0 7 theme potential 47:55 arg1 site 80:83 an additional potential N-linked glycosylation site 33:83 an additional potential N-linked glycosylation site at residue 133 in hemagglutinin 33:115 The S128N mutation combined with an additional potential N-linked glycosylation site at residue 133 in hemagglutinin affects the antigenicity of the human H7N9 virus. 27381217 0 8 theme human 149:153 arg1 virus 160:164 the human H7N9 virus 145:164 the human H7N9 virus 145:164 The S128N mutation combined with an additional potential N-linked glycosylation site at residue 133 in hemagglutinin affects the antigenicity of the human H7N9 virus. 27381217 0 9 theme N-linked 57:64 arg1 site 80:83 an additional potential N-linked glycosylation site 33:83 an additional potential N-linked glycosylation site at residue 133 in hemagglutinin 33:115 The S128N mutation combined with an additional potential N-linked glycosylation site at residue 133 in hemagglutinin affects the antigenicity of the human H7N9 virus. 27381217 0 10 gly glycosylation 66:78 arg2 residue 88:94 residue 133 88:98 residue 133 88:98 The S128N mutation combined with an additional potential N-linked glycosylation site at residue 133 in hemagglutinin affects the antigenicity of the human H7N9 virus. 27381217 0 10 gly glycosylation 66:78 arg2 site 80:83 an additional potential N-linked glycosylation site 33:83 an additional potential N-linked glycosylation site at residue 133 in hemagglutinin 33:115 The S128N mutation combined with an additional potential N-linked glycosylation site at residue 133 in hemagglutinin affects the antigenicity of the human H7N9 virus. 27381217 0 11 theme additional 36:45 arg1 site 80:83 an additional potential N-linked glycosylation site 33:83 an additional potential N-linked glycosylation site at residue 133 in hemagglutinin 33:115 The S128N mutation combined with an additional potential N-linked glycosylation site at residue 133 in hemagglutinin affects the antigenicity of the human H7N9 virus. 28661051 8 0 gly unglycosylated 1513:1526 arg1 subunits 1530:1537 unglycosylated a subunits 1513:1537 unglycosylated a subunits 1513:1537 Immunofluorescence colocalization analysis showed that unglycosylated a subunits were retained in the ER, and co-immunoprecipitation studies showed that they were unable to associate with the V-ATPase assembly chaperone, VMA21. 28661051 0 1 link N-linked 0:7 arg1 glycosylation 9:21 N-linked glycosylation 0:21 N-linked glycosylation of a subunit isoforms 0:43 N-linked glycosylation of a subunit isoforms is critical for vertebrate vacuolar H+ -ATPase (V-ATPase) biosynthesis. 28661051 9 2 theme V-ATPase 1912:1919 arg1 complexes 1921:1929 V-ATPase complexes 1912:1929 V-ATPase complexes 1912:1929 Taken together with our previous a4 subunit studies, these observations show that N-glycosylation is crucial in all four human V-ATPase a subunit isoforms for protein stability and ultimately for functional incorporation into V-ATPase complexes. 28661051 1 3 theme sector 161:166 arg1 subunit 123:129 The a subunit 117:129 The a subunit of the V0 membrane-integrated sector of human V-ATPase 117:184 The a subunit of the V0 membrane-integrated sector of human V-ATPase has four isoforms, a1-a4, with diverse and crucial functions in health and disease. 28661051 4 4 theme putative 806:813 arg1 sites 831:835 putative N-glycosylation sites 806:835 putative N-glycosylation sites 806:835 Here we extend our investigation to the other isoforms by transiently transfecting HEK 293 cells to express cDNA constructs of epitope-tagged human a1-a3 subunits, with or without mutations that convert Asn to Gln at putative N-glycosylation sites. 28661051 4 5 theme other 629:633 arg1 isoforms 635:642 the other isoforms 625:642 the other isoforms 625:642 Here we extend our investigation to the other isoforms by transiently transfecting HEK 293 cells to express cDNA constructs of epitope-tagged human a1-a3 subunits, with or without mutations that convert Asn to Gln at putative N-glycosylation sites. 28661051 1 6 theme human 171:175 arg1 V-ATPase 177:184 human V-ATPase 171:184 human V-ATPase 171:184 The a subunit of the V0 membrane-integrated sector of human V-ATPase has four isoforms, a1-a4, with diverse and crucial functions in health and disease. 28661051 9 7 from crucial 1787:1793 arg1 isoforms 1832:1839 all four human V-ATPase a subunit isoforms 1798:1839 all four human V-ATPase a subunit isoforms 1798:1839 Taken together with our previous a4 subunit studies, these observations show that N-glycosylation is crucial in all four human V-ATPase a subunit isoforms for protein stability and ultimately for functional incorporation into V-ATPase complexes. 28661051 1 8 from functions 237:245 arg1 disease 261:267 disease 261:267 disease 261:267 The a subunit of the V0 membrane-integrated sector of human V-ATPase has four isoforms, a1-a4, with diverse and crucial functions in health and disease. 28661051 1 8 from functions 237:245 arg1 health 250:255 health 250:255 health 250:255 The a subunit of the V0 membrane-integrated sector of human V-ATPase has four isoforms, a1-a4, with diverse and crucial functions in health and disease. 28661051 2 9 contain have 354:357 arg2 sequons 398:404 positionally conserved N-glycosylation sequons 359:404 positionally conserved N-glycosylation sequons 359:404 They are encoded by four conserved paralogous genes, and their vertebrate orthologs have positionally conserved N-glycosylation sequons within the second extracellular loop, EL2, of the a subunit membrane domain. 28661051 2 9 contain have 354:357 arg1 orthologs 344:352 their vertebrate orthologs 327:352 their vertebrate orthologs 327:352 They are encoded by four conserved paralogous genes, and their vertebrate orthologs have positionally conserved N-glycosylation sequons within the second extracellular loop, EL2, of the a subunit membrane domain. 28661051 9 10 theme V-ATPase 1813:1820 arg1 isoforms 1832:1839 all four human V-ATPase a subunit isoforms 1798:1839 all four human V-ATPase a subunit isoforms 1798:1839 Taken together with our previous a4 subunit studies, these observations show that N-glycosylation is crucial in all four human V-ATPase a subunit isoforms for protein stability and ultimately for functional incorporation into V-ATPase complexes. 28661051 9 11 theme subunit 1824:1830 arg1 isoforms 1832:1839 all four human V-ATPase a subunit isoforms 1798:1839 all four human V-ATPase a subunit isoforms 1798:1839 Taken together with our previous a4 subunit studies, these observations show that N-glycosylation is crucial in all four human V-ATPase a subunit isoforms for protein stability and ultimately for functional incorporation into V-ATPase complexes. 28661051 6 12 theme a 1243:1243 arg1 subunits 1245:1252 wild-type a subunits 1233:1252 wild-type a subunits 1233:1252 All unglycosylated mutants, where predicted N-glycosylation sites had been eliminated by sequon mutagenesis, showed increased relative mobility on immunoblots, identical to what was seen for wild-type a subunits after enzymatic deglycosylation. 28661051 5 13 theme mobility 910:917 arg1 shifts 919:924 mobility shifts 910:924 mobility shifts 910:924 Expression and N-glycosylation were characterized by immunoblotting and mobility shifts after enzymatic deglycosylation, and intracellular localization was determined using immunofluorescence microscopy. 28661051 9 14 from isoforms 1832:1839 arg1 crucial 1787:1793 crucial 1787:1793 crucial 1787:1793 Taken together with our previous a4 subunit studies, these observations show that N-glycosylation is crucial in all four human V-ATPase a subunit isoforms for protein stability and ultimately for functional incorporation into V-ATPase complexes. 28661051 2 15 theme membrane 466:473 arg1 domain 475:480 a subunit membrane domain 456:480 the a subunit membrane domain 452:480 They are encoded by four conserved paralogous genes, and their vertebrate orthologs have positionally conserved N-glycosylation sequons within the second extracellular loop, EL2, of the a subunit membrane domain. 28661051 0 16 theme vacuolar 72:79 arg1 V-ATPase 93:100 V-ATPase 93:100 V-ATPase 93:100 N-linked glycosylation of a subunit isoforms is critical for vertebrate vacuolar H+ -ATPase (V-ATPase) biosynthesis. 28661051 0 16 theme vacuolar 72:79 arg1 -ATPase 84:90 vacuolar H+ -ATPase 72:90 vertebrate vacuolar H+ -ATPase (V-ATPase) biosynthesis 61:114 N-linked glycosylation of a subunit isoforms is critical for vertebrate vacuolar H+ -ATPase (V-ATPase) biosynthesis. 28661051 4 17 from sites 831:835 arg1 Asn 792:794 Asn 792:794 Asn to Gln at putative N-glycosylation sites 792:835 Here we extend our investigation to the other isoforms by transiently transfecting HEK 293 cells to express cDNA constructs of epitope-tagged human a1-a3 subunits, with or without mutations that convert Asn to Gln at putative N-glycosylation sites. 28661051 1 18 theme V0 138:139 arg1 sector 161:166 the V0 membrane-integrated sector 134:166 the V0 membrane-integrated sector of human V-ATPase 134:184 The a subunit of the V0 membrane-integrated sector of human V-ATPase has four isoforms, a1-a4, with diverse and crucial functions in health and disease. 28661051 4 19 theme human 731:735 arg1 subunits 743:750 epitope-tagged human a1-a3 subunits 716:750 epitope-tagged human a1-a3 subunits 716:750 Here we extend our investigation to the other isoforms by transiently transfecting HEK 293 cells to express cDNA constructs of epitope-tagged human a1-a3 subunits, with or without mutations that convert Asn to Gln at putative N-glycosylation sites. 28661051 0 20 theme -ATPase 84:90 arg1 biosynthesis 103:114 vertebrate vacuolar H+ -ATPase (V-ATPase) biosynthesis 61:114 vertebrate vacuolar H+ -ATPase (V-ATPase) biosynthesis 61:114 N-linked glycosylation of a subunit isoforms is critical for vertebrate vacuolar H+ -ATPase (V-ATPase) biosynthesis. 28661051 1 21 theme a 121:121 arg1 subunit 123:129 The a subunit 117:129 The a subunit of the V0 membrane-integrated sector of human V-ATPase 117:184 The a subunit of the V0 membrane-integrated sector of human V-ATPase has four isoforms, a1-a4, with diverse and crucial functions in health and disease. 28661051 9 22 theme functional 1882:1891 arg1 incorporation 1893:1905 functional incorporation 1882:1905 functional incorporation into V-ATPase complexes 1882:1929 Taken together with our previous a4 subunit studies, these observations show that N-glycosylation is crucial in all four human V-ATPase a subunit isoforms for protein stability and ultimately for functional incorporation into V-ATPase complexes. 28661051 4 23 theme subunits 743:750 arg1 constructs 702:711 cDNA constructs 697:711 cDNA constructs of epitope-tagged human a1-a3 subunits 697:750 Here we extend our investigation to the other isoforms by transiently transfecting HEK 293 cells to express cDNA constructs of epitope-tagged human a1-a3 subunits, with or without mutations that convert Asn to Gln at putative N-glycosylation sites. 28661051 7 24 from degradation 1418:1428 arg1 pathway 1449:1455 the proteasomal pathway 1433:1455 the proteasomal pathway 1433:1455 Cycloheximide-chase experiments showed that unglycosylated subunits were turned over at a higher rate than N-glycosylated forms by degradation in the proteasomal pathway. 28661051 7 25 theme N-glycosylated 1394:1407 arg1 forms 1409:1413 N-glycosylated forms 1394:1413 N-glycosylated forms 1394:1413 Cycloheximide-chase experiments showed that unglycosylated subunits were turned over at a higher rate than N-glycosylated forms by degradation in the proteasomal pathway. 28661051 4 26 theme cDNA 697:700 arg1 constructs 702:711 cDNA constructs 697:711 cDNA constructs of epitope-tagged human a1-a3 subunits 697:750 Here we extend our investigation to the other isoforms by transiently transfecting HEK 293 cells to express cDNA constructs of epitope-tagged human a1-a3 subunits, with or without mutations that convert Asn to Gln at putative N-glycosylation sites. 28661051 0 27 theme N-linked 0:7 arg1 glycosylation 9:21 N-linked glycosylation 0:21 N-linked glycosylation of a subunit isoforms 0:43 N-linked glycosylation of a subunit isoforms is critical for vertebrate vacuolar H+ -ATPase (V-ATPase) biosynthesis. 28661051 6 28 theme N-glycosylation 1086:1100 arg1 sites 1102:1106 predicted N-glycosylation sites 1076:1106 predicted N-glycosylation sites 1076:1106 All unglycosylated mutants, where predicted N-glycosylation sites had been eliminated by sequon mutagenesis, showed increased relative mobility on immunoblots, identical to what was seen for wild-type a subunits after enzymatic deglycosylation. 28661051 2 29 theme second 417:422 arg1 EL2 444:446 EL2 444:446 EL2 444:446 They are encoded by four conserved paralogous genes, and their vertebrate orthologs have positionally conserved N-glycosylation sequons within the second extracellular loop, EL2, of the a subunit membrane domain. 28661051 2 29 theme second 417:422 arg1 loop 438:441 the second extracellular loop 413:441 the second extracellular loop 413:441 They are encoded by four conserved paralogous genes, and their vertebrate orthologs have positionally conserved N-glycosylation sequons within the second extracellular loop, EL2, of the a subunit membrane domain. 28661051 6 30 from mobility 1177:1184 arg1 immunoblots 1189:1199 immunoblots 1189:1199 immunoblots 1189:1199 All unglycosylated mutants, where predicted N-glycosylation sites had been eliminated by sequon mutagenesis, showed increased relative mobility on immunoblots, identical to what was seen for wild-type a subunits after enzymatic deglycosylation. 28661051 1 31 with isoforms 195:202 arg1 functions 237:245 diverse and crucial functions 217:245 diverse and crucial functions in health and disease 217:267 The a subunit of the V0 membrane-integrated sector of human V-ATPase has four isoforms, a1-a4, with diverse and crucial functions in health and disease. 28661051 8 32 theme V-ATPase 1650:1657 arg1 VMA21 1679:1683 VMA21 1679:1683 VMA21 1679:1683 Immunofluorescence colocalization analysis showed that unglycosylated a subunits were retained in the ER, and co-immunoprecipitation studies showed that they were unable to associate with the V-ATPase assembly chaperone, VMA21. 28661051 8 32 theme V-ATPase 1650:1657 arg1 chaperone 1668:1676 the V-ATPase assembly chaperone 1646:1676 the V-ATPase assembly chaperone 1646:1676 Immunofluorescence colocalization analysis showed that unglycosylated a subunits were retained in the ER, and co-immunoprecipitation studies showed that they were unable to associate with the V-ATPase assembly chaperone, VMA21. 28661051 8 33 theme colocalization 1477:1490 arg1 analysis 1492:1499 Immunofluorescence colocalization analysis 1458:1499 Immunofluorescence colocalization analysis 1458:1499 Immunofluorescence colocalization analysis showed that unglycosylated a subunits were retained in the ER, and co-immunoprecipitation studies showed that they were unable to associate with the V-ATPase assembly chaperone, VMA21. 28661051 2 34 theme N-glycosylation 382:396 arg1 sequons 398:404 positionally conserved N-glycosylation sequons 359:404 positionally conserved N-glycosylation sequons 359:404 They are encoded by four conserved paralogous genes, and their vertebrate orthologs have positionally conserved N-glycosylation sequons within the second extracellular loop, EL2, of the a subunit membrane domain. 28661051 1 35 theme membrane-integrated 141:159 arg1 sector 161:166 the V0 membrane-integrated sector 134:166 the V0 membrane-integrated sector of human V-ATPase 134:184 The a subunit of the V0 membrane-integrated sector of human V-ATPase has four isoforms, a1-a4, with diverse and crucial functions in health and disease. 28661051 0 36 theme subunit 28:34 arg1 isoforms 36:43 a subunit isoforms 26:43 a subunit isoforms 26:43 N-linked glycosylation of a subunit isoforms is critical for vertebrate vacuolar H+ -ATPase (V-ATPase) biosynthesis. 28661051 0 37 gly glycosylation 9:21 arg1 isoforms 36:43 a subunit isoforms 26:43 a subunit isoforms 26:43 N-linked glycosylation of a subunit isoforms is critical for vertebrate vacuolar H+ -ATPase (V-ATPase) biosynthesis. 28661051 0 37 gly glycosylation 9:21 arg1 V-ATPase 93:100 V-ATPase 93:100 V-ATPase 93:100 N-linked glycosylation of a subunit isoforms is critical for vertebrate vacuolar H+ -ATPase (V-ATPase) biosynthesis. 28661051 0 37 gly glycosylation 9:21 arg1 -ATPase 84:90 vacuolar H+ -ATPase 72:90 vertebrate vacuolar H+ -ATPase (V-ATPase) biosynthesis 61:114 N-linked glycosylation of a subunit isoforms is critical for vertebrate vacuolar H+ -ATPase (V-ATPase) biosynthesis. 28661051 2 38 theme subunit 458:464 arg1 domain 475:480 a subunit membrane domain 456:480 the a subunit membrane domain 452:480 They are encoded by four conserved paralogous genes, and their vertebrate orthologs have positionally conserved N-glycosylation sequons within the second extracellular loop, EL2, of the a subunit membrane domain. 28661051 2 39 theme paralogous 305:314 arg1 genes 316:320 four conserved paralogous genes 290:320 four conserved paralogous genes 290:320 They are encoded by four conserved paralogous genes, and their vertebrate orthologs have positionally conserved N-glycosylation sequons within the second extracellular loop, EL2, of the a subunit membrane domain. 28661051 6 40 theme increased 1158:1166 arg1 mobility 1177:1184 increased relative mobility 1158:1184 increased relative mobility on immunoblots, identical to what was seen for wild-type a subunits after enzymatic deglycosylation 1158:1284 All unglycosylated mutants, where predicted N-glycosylation sites had been eliminated by sequon mutagenesis, showed increased relative mobility on immunoblots, identical to what was seen for wild-type a subunits after enzymatic deglycosylation. 28661051 6 41 gly N-glycosylation 1086:1100 arg2 sites 1102:1106 predicted N-glycosylation sites 1076:1106 predicted N-glycosylation sites 1076:1106 All unglycosylated mutants, where predicted N-glycosylation sites had been eliminated by sequon mutagenesis, showed increased relative mobility on immunoblots, identical to what was seen for wild-type a subunits after enzymatic deglycosylation. 28661051 8 42 theme unglycosylated 1513:1526 arg1 subunits 1530:1537 unglycosylated a subunits 1513:1537 unglycosylated a subunits 1513:1537 Immunofluorescence colocalization analysis showed that unglycosylated a subunits were retained in the ER, and co-immunoprecipitation studies showed that they were unable to associate with the V-ATPase assembly chaperone, VMA21. 28661051 9 43 theme a4 1719:1720 arg1 studies 1730:1736 our previous a4 subunit studies 1706:1736 our previous a4 subunit studies 1706:1736 Taken together with our previous a4 subunit studies, these observations show that N-glycosylation is crucial in all four human V-ATPase a subunit isoforms for protein stability and ultimately for functional incorporation into V-ATPase complexes. 28661051 7 44 theme unglycosylated 1331:1344 arg1 subunits 1346:1353 unglycosylated subunits 1331:1353 unglycosylated subunits 1331:1353 Cycloheximide-chase experiments showed that unglycosylated subunits were turned over at a higher rate than N-glycosylated forms by degradation in the proteasomal pathway. 28661051 6 45 gly unglycosylated 1046:1059 arg1 mutants 1061:1067 All unglycosylated mutants 1042:1067 All unglycosylated mutants 1042:1067 All unglycosylated mutants, where predicted N-glycosylation sites had been eliminated by sequon mutagenesis, showed increased relative mobility on immunoblots, identical to what was seen for wild-type a subunits after enzymatic deglycosylation. 28661051 5 46 theme immunofluorescence 1011:1028 arg1 microscopy 1030:1039 immunofluorescence microscopy 1011:1039 immunofluorescence microscopy 1011:1039 Expression and N-glycosylation were characterized by immunoblotting and mobility shifts after enzymatic deglycosylation, and intracellular localization was determined using immunofluorescence microscopy. 28661051 6 47 theme sequon 1131:1136 arg1 mutagenesis 1138:1148 sequon mutagenesis 1131:1148 sequon mutagenesis 1131:1148 All unglycosylated mutants, where predicted N-glycosylation sites had been eliminated by sequon mutagenesis, showed increased relative mobility on immunoblots, identical to what was seen for wild-type a subunits after enzymatic deglycosylation. 28661051 1 48 theme diverse 217:223 arg1 functions 237:245 diverse and crucial functions 217:245 diverse and crucial functions in health and disease 217:267 The a subunit of the V0 membrane-integrated sector of human V-ATPase has four isoforms, a1-a4, with diverse and crucial functions in health and disease. 28661051 4 49 theme N-glycosylation 815:829 arg1 sites 831:835 putative N-glycosylation sites 806:835 putative N-glycosylation sites 806:835 Here we extend our investigation to the other isoforms by transiently transfecting HEK 293 cells to express cDNA constructs of epitope-tagged human a1-a3 subunits, with or without mutations that convert Asn to Gln at putative N-glycosylation sites. 28661051 7 50 theme Cycloheximide-chase 1287:1305 arg1 experiments 1307:1317 Cycloheximide-chase experiments 1287:1317 Cycloheximide-chase experiments 1287:1317 Cycloheximide-chase experiments showed that unglycosylated subunits were turned over at a higher rate than N-glycosylated forms by degradation in the proteasomal pathway. 28661051 1 51 theme crucial 229:235 arg1 functions 237:245 diverse and crucial functions 217:245 diverse and crucial functions in health and disease 217:267 The a subunit of the V0 membrane-integrated sector of human V-ATPase has four isoforms, a1-a4, with diverse and crucial functions in health and disease. 28661051 4 52 gly N-glycosylation 815:829 arg2 sites 831:835 putative N-glycosylation sites 806:835 putative N-glycosylation sites 806:835 Here we extend our investigation to the other isoforms by transiently transfecting HEK 293 cells to express cDNA constructs of epitope-tagged human a1-a3 subunits, with or without mutations that convert Asn to Gln at putative N-glycosylation sites. 28661051 6 53 theme identical 1202:1210 arg1 immunoblots 1189:1199 immunoblots 1189:1199 immunoblots 1189:1199 All unglycosylated mutants, where predicted N-glycosylation sites had been eliminated by sequon mutagenesis, showed increased relative mobility on immunoblots, identical to what was seen for wild-type a subunits after enzymatic deglycosylation. 28661051 3 54 gly N-glycosylated 573:586 arg1 N-glycosylated 573:586 N-glycosylated 573:586 N-glycosylated 573:586 Previously, we have shown directly that the predicted sequon for the a4 isoform is indeed N-glycosylated. 28661051 3 54 gly N-glycosylated 573:586 arg1 sequon 537:542 the predicted sequon 523:542 the predicted sequon for the a4 isoform 523:561 Previously, we have shown directly that the predicted sequon for the a4 isoform is indeed N-glycosylated. 28661051 3 55 theme predicted 527:535 arg1 N-glycosylated 573:586 N-glycosylated 573:586 N-glycosylated 573:586 Previously, we have shown directly that the predicted sequon for the a4 isoform is indeed N-glycosylated. 28661051 3 55 theme predicted 527:535 arg1 sequon 537:542 the predicted sequon 523:542 the predicted sequon for the a4 isoform 523:561 Previously, we have shown directly that the predicted sequon for the a4 isoform is indeed N-glycosylated. 28661051 1 56 theme V-ATPase 177:184 arg1 sector 161:166 the V0 membrane-integrated sector 134:166 the V0 membrane-integrated sector of human V-ATPase 134:184 The a subunit of the V0 membrane-integrated sector of human V-ATPase has four isoforms, a1-a4, with diverse and crucial functions in health and disease. 28661051 3 57 theme a4 552:553 arg1 isoform 555:561 the a4 isoform 548:561 the a4 isoform 548:561 Previously, we have shown directly that the predicted sequon for the a4 isoform is indeed N-glycosylated. 28661051 9 58 theme human 1807:1811 arg1 isoforms 1832:1839 all four human V-ATPase a subunit isoforms 1798:1839 all four human V-ATPase a subunit isoforms 1798:1839 Taken together with our previous a4 subunit studies, these observations show that N-glycosylation is crucial in all four human V-ATPase a subunit isoforms for protein stability and ultimately for functional incorporation into V-ATPase complexes. 28661051 6 59 theme enzymatic 1260:1268 arg1 deglycosylation 1270:1284 enzymatic deglycosylation 1260:1284 enzymatic deglycosylation 1260:1284 All unglycosylated mutants, where predicted N-glycosylation sites had been eliminated by sequon mutagenesis, showed increased relative mobility on immunoblots, identical to what was seen for wild-type a subunits after enzymatic deglycosylation. 28661051 9 60 theme a 1822:1822 arg1 isoforms 1832:1839 all four human V-ATPase a subunit isoforms 1798:1839 all four human V-ATPase a subunit isoforms 1798:1839 Taken together with our previous a4 subunit studies, these observations show that N-glycosylation is crucial in all four human V-ATPase a subunit isoforms for protein stability and ultimately for functional incorporation into V-ATPase complexes. 28661051 7 61 theme proteasomal 1437:1447 arg1 pathway 1449:1455 the proteasomal pathway 1433:1455 the proteasomal pathway 1433:1455 Cycloheximide-chase experiments showed that unglycosylated subunits were turned over at a higher rate than N-glycosylated forms by degradation in the proteasomal pathway. 28661051 4 62 theme HEK 672:674 arg1 cells 680:684 HEK 293 cells 672:684 HEK 293 cells to express cDNA constructs of epitope-tagged human a1-a3 subunits 672:750 Here we extend our investigation to the other isoforms by transiently transfecting HEK 293 cells to express cDNA constructs of epitope-tagged human a1-a3 subunits, with or without mutations that convert Asn to Gln at putative N-glycosylation sites. 28661051 6 63 theme unglycosylated 1046:1059 arg1 mutants 1061:1067 All unglycosylated mutants 1042:1067 All unglycosylated mutants 1042:1067 All unglycosylated mutants, where predicted N-glycosylation sites had been eliminated by sequon mutagenesis, showed increased relative mobility on immunoblots, identical to what was seen for wild-type a subunits after enzymatic deglycosylation. 28661051 8 64 theme co-immunoprecipitation 1568:1589 arg1 studies 1591:1597 co-immunoprecipitation studies 1568:1597 co-immunoprecipitation studies 1568:1597 Immunofluorescence colocalization analysis showed that unglycosylated a subunits were retained in the ER, and co-immunoprecipitation studies showed that they were unable to associate with the V-ATPase assembly chaperone, VMA21. 28661051 6 65 theme wild-type 1233:1241 arg1 subunits 1245:1252 wild-type a subunits 1233:1252 wild-type a subunits 1233:1252 All unglycosylated mutants, where predicted N-glycosylation sites had been eliminated by sequon mutagenesis, showed increased relative mobility on immunoblots, identical to what was seen for wild-type a subunits after enzymatic deglycosylation. 28661051 0 66 theme vertebrate 61:70 arg1 biosynthesis 103:114 vertebrate vacuolar H+ -ATPase (V-ATPase) biosynthesis 61:114 vertebrate vacuolar H+ -ATPase (V-ATPase) biosynthesis 61:114 N-linked glycosylation of a subunit isoforms is critical for vertebrate vacuolar H+ -ATPase (V-ATPase) biosynthesis. 28661051 9 67 theme protein 1845:1851 arg1 stability 1853:1861 protein stability 1845:1861 protein stability 1845:1861 Taken together with our previous a4 subunit studies, these observations show that N-glycosylation is crucial in all four human V-ATPase a subunit isoforms for protein stability and ultimately for functional incorporation into V-ATPase complexes. 28661051 0 68 theme H+ 81:82 arg1 V-ATPase 93:100 V-ATPase 93:100 V-ATPase 93:100 N-linked glycosylation of a subunit isoforms is critical for vertebrate vacuolar H+ -ATPase (V-ATPase) biosynthesis. 28661051 0 68 theme H+ 81:82 arg1 -ATPase 84:90 vacuolar H+ -ATPase 72:90 vertebrate vacuolar H+ -ATPase (V-ATPase) biosynthesis 61:114 N-linked glycosylation of a subunit isoforms is critical for vertebrate vacuolar H+ -ATPase (V-ATPase) biosynthesis. 28661051 2 69 gly N-glycosylation 382:396 arg2 sequons 398:404 positionally conserved N-glycosylation sequons 359:404 positionally conserved N-glycosylation sequons 359:404 They are encoded by four conserved paralogous genes, and their vertebrate orthologs have positionally conserved N-glycosylation sequons within the second extracellular loop, EL2, of the a subunit membrane domain. 28661051 4 70 theme epitope-tagged 716:729 arg1 subunits 743:750 epitope-tagged human a1-a3 subunits 716:750 epitope-tagged human a1-a3 subunits 716:750 Here we extend our investigation to the other isoforms by transiently transfecting HEK 293 cells to express cDNA constructs of epitope-tagged human a1-a3 subunits, with or without mutations that convert Asn to Gln at putative N-glycosylation sites. 28661051 7 71 gly N-glycosylated 1394:1407 arg1 forms 1409:1413 N-glycosylated forms 1394:1413 N-glycosylated forms 1394:1413 Cycloheximide-chase experiments showed that unglycosylated subunits were turned over at a higher rate than N-glycosylated forms by degradation in the proteasomal pathway. 28661051 5 72 theme intracellular 963:975 arg1 localization 977:988 intracellular localization 963:988 intracellular localization 963:988 Expression and N-glycosylation were characterized by immunoblotting and mobility shifts after enzymatic deglycosylation, and intracellular localization was determined using immunofluorescence microscopy. 28661051 2 73 theme domain 475:480 arg1 EL2 444:446 EL2 444:446 EL2 444:446 They are encoded by four conserved paralogous genes, and their vertebrate orthologs have positionally conserved N-glycosylation sequons within the second extracellular loop, EL2, of the a subunit membrane domain. 28661051 2 73 theme domain 475:480 arg1 loop 438:441 the second extracellular loop 413:441 the second extracellular loop 413:441 They are encoded by four conserved paralogous genes, and their vertebrate orthologs have positionally conserved N-glycosylation sequons within the second extracellular loop, EL2, of the a subunit membrane domain. 28661051 4 74 theme a1-a3 737:741 arg1 subunits 743:750 epitope-tagged human a1-a3 subunits 716:750 epitope-tagged human a1-a3 subunits 716:750 Here we extend our investigation to the other isoforms by transiently transfecting HEK 293 cells to express cDNA constructs of epitope-tagged human a1-a3 subunits, with or without mutations that convert Asn to Gln at putative N-glycosylation sites. 28661051 7 75 theme higher 1377:1382 arg1 rate 1384:1387 a higher rate 1375:1387 a higher rate than N-glycosylated forms by degradation in the proteasomal pathway 1375:1455 Cycloheximide-chase experiments showed that unglycosylated subunits were turned over at a higher rate than N-glycosylated forms by degradation in the proteasomal pathway. 28661051 2 76 theme extracellular 424:436 arg1 EL2 444:446 EL2 444:446 EL2 444:446 They are encoded by four conserved paralogous genes, and their vertebrate orthologs have positionally conserved N-glycosylation sequons within the second extracellular loop, EL2, of the a subunit membrane domain. 28661051 2 76 theme extracellular 424:436 arg1 loop 438:441 the second extracellular loop 413:441 the second extracellular loop 413:441 They are encoded by four conserved paralogous genes, and their vertebrate orthologs have positionally conserved N-glycosylation sequons within the second extracellular loop, EL2, of the a subunit membrane domain. 28661051 2 77 theme vertebrate 333:342 arg1 orthologs 344:352 their vertebrate orthologs 327:352 their vertebrate orthologs 327:352 They are encoded by four conserved paralogous genes, and their vertebrate orthologs have positionally conserved N-glycosylation sequons within the second extracellular loop, EL2, of the a subunit membrane domain. 28661051 0 78 theme a 26:26 arg1 isoforms 36:43 a subunit isoforms 26:43 a subunit isoforms 26:43 N-linked glycosylation of a subunit isoforms is critical for vertebrate vacuolar H+ -ATPase (V-ATPase) biosynthesis. 28661051 5 79 theme enzymatic 932:940 arg1 deglycosylation 942:956 enzymatic deglycosylation 932:956 enzymatic deglycosylation 932:956 Expression and N-glycosylation were characterized by immunoblotting and mobility shifts after enzymatic deglycosylation, and intracellular localization was determined using immunofluorescence microscopy. 28661051 6 80 theme predicted 1076:1084 arg1 sites 1102:1106 predicted N-glycosylation sites 1076:1106 predicted N-glycosylation sites 1076:1106 All unglycosylated mutants, where predicted N-glycosylation sites had been eliminated by sequon mutagenesis, showed increased relative mobility on immunoblots, identical to what was seen for wild-type a subunits after enzymatic deglycosylation. 28661051 8 81 theme assembly 1659:1666 arg1 VMA21 1679:1683 VMA21 1679:1683 VMA21 1679:1683 Immunofluorescence colocalization analysis showed that unglycosylated a subunits were retained in the ER, and co-immunoprecipitation studies showed that they were unable to associate with the V-ATPase assembly chaperone, VMA21. 28661051 8 81 theme assembly 1659:1666 arg1 chaperone 1668:1676 the V-ATPase assembly chaperone 1646:1676 the V-ATPase assembly chaperone 1646:1676 Immunofluorescence colocalization analysis showed that unglycosylated a subunits were retained in the ER, and co-immunoprecipitation studies showed that they were unable to associate with the V-ATPase assembly chaperone, VMA21. 28661051 0 82 theme isoforms 36:43 arg1 glycosylation 9:21 N-linked glycosylation 0:21 N-linked glycosylation of a subunit isoforms 0:43 N-linked glycosylation of a subunit isoforms is critical for vertebrate vacuolar H+ -ATPase (V-ATPase) biosynthesis. 28661051 8 83 theme Immunofluorescence 1458:1475 arg1 analysis 1492:1499 Immunofluorescence colocalization analysis 1458:1499 Immunofluorescence colocalization analysis 1458:1499 Immunofluorescence colocalization analysis showed that unglycosylated a subunits were retained in the ER, and co-immunoprecipitation studies showed that they were unable to associate with the V-ATPase assembly chaperone, VMA21. 28661051 2 84 theme conserved 372:380 arg1 sequons 398:404 positionally conserved N-glycosylation sequons 359:404 positionally conserved N-glycosylation sequons 359:404 They are encoded by four conserved paralogous genes, and their vertebrate orthologs have positionally conserved N-glycosylation sequons within the second extracellular loop, EL2, of the a subunit membrane domain. 28661051 6 85 theme relative 1168:1175 arg1 mobility 1177:1184 increased relative mobility 1158:1184 increased relative mobility on immunoblots, identical to what was seen for wild-type a subunits after enzymatic deglycosylation 1158:1284 All unglycosylated mutants, where predicted N-glycosylation sites had been eliminated by sequon mutagenesis, showed increased relative mobility on immunoblots, identical to what was seen for wild-type a subunits after enzymatic deglycosylation. 28661051 2 86 theme conserved 295:303 arg1 genes 316:320 four conserved paralogous genes 290:320 four conserved paralogous genes 290:320 They are encoded by four conserved paralogous genes, and their vertebrate orthologs have positionally conserved N-glycosylation sequons within the second extracellular loop, EL2, of the a subunit membrane domain. 28661051 7 87 gly unglycosylated 1331:1344 arg1 subunits 1346:1353 unglycosylated subunits 1331:1353 unglycosylated subunits 1331:1353 Cycloheximide-chase experiments showed that unglycosylated subunits were turned over at a higher rate than N-glycosylated forms by degradation in the proteasomal pathway. 28661051 9 88 theme previous 1710:1717 arg1 studies 1730:1736 our previous a4 subunit studies 1706:1736 our previous a4 subunit studies 1706:1736 Taken together with our previous a4 subunit studies, these observations show that N-glycosylation is crucial in all four human V-ATPase a subunit isoforms for protein stability and ultimately for functional incorporation into V-ATPase complexes. 28661051 1 89 contain has 186:188 arg2 isoforms 195:202 four isoforms 190:202 four isoforms 190:202 The a subunit of the V0 membrane-integrated sector of human V-ATPase has four isoforms, a1-a4, with diverse and crucial functions in health and disease. 28661051 1 89 contain has 186:188 arg2 a1-a4 205:209 a1-a4 205:209 a1-a4 205:209 The a subunit of the V0 membrane-integrated sector of human V-ATPase has four isoforms, a1-a4, with diverse and crucial functions in health and disease. 28661051 1 89 contain has 186:188 arg1 subunit 123:129 The a subunit 117:129 The a subunit of the V0 membrane-integrated sector of human V-ATPase 117:184 The a subunit of the V0 membrane-integrated sector of human V-ATPase has four isoforms, a1-a4, with diverse and crucial functions in health and disease. 28661051 9 90 theme subunit 1722:1728 arg1 studies 1730:1736 our previous a4 subunit studies 1706:1736 our previous a4 subunit studies 1706:1736 Taken together with our previous a4 subunit studies, these observations show that N-glycosylation is crucial in all four human V-ATPase a subunit isoforms for protein stability and ultimately for functional incorporation into V-ATPase complexes. 28661051 8 91 theme a 1528:1528 arg1 subunits 1530:1537 unglycosylated a subunits 1513:1537 unglycosylated a subunits 1513:1537 Immunofluorescence colocalization analysis showed that unglycosylated a subunits were retained in the ER, and co-immunoprecipitation studies showed that they were unable to associate with the V-ATPase assembly chaperone, VMA21. 25862406 5 0 theme single 512:517 arg1 band 519:522 a single band 510:522 a single band of 50kDa corresponding to the unglycosylated protein 510:575 N163/212Q displayed a single band of 50kDa corresponding to the unglycosylated protein. 25862406 6 1 theme WT 606:607 arg1 membrane 594:601 membrane 594:601 membrane of WT and mutants 594:619 The presence in membrane of WT and mutants was evaluated by protein biotinylation assay followed by immunoblotting. 25862406 11 2 theme ASCT2 1239:1243 arg1 endocytosis 1224:1234 endocytosis 1224:1234 endocytosis of ASCT2 1224:1243 The rate of endocytosis of ASCT2 was assayed by a reversible biotinylation strategy. 25862406 4 3 from 50kDa 483:487 arg1 masses 462:467 apparent molecular masses 443:467 apparent molecular masses from 80kDa to 50kDa 443:487 N163Q and N212Q displayed multiple bands with apparent molecular masses from 80kDa to 50kDa. 25862406 16 4 theme WT 1675:1676 arg1 protein 1678:1684 One hour after brefeldin removal WT protein 1642:1684 One hour after brefeldin removal WT protein 1642:1684 One hour after brefeldin removal WT protein was localized to the plasma membrane while the double mutant was localized in the cytosol. 25862406 1 5 theme large 214:218 arg1 loop 234:237 the large extracellular loop 210:237 the large extracellular loop 210:237 The human amino acid transporter SLC1A5 (ASCT2) contains two N-glycosylation sites (N163 and N212) located in the large extracellular loop. 25862406 9 6 theme reduced 946:952 arg1 activity 964:971 a strongly reduced transport activity 935:971 a strongly reduced transport activity correlating with reduced surface expression 935:1015 N163/212Q exhibited a strongly reduced transport activity correlating with reduced surface expression. 25862406 1 7 gly N-glycosylation 161:175 arg2 N212 193:196 N212 193:196 N212 193:196 The human amino acid transporter SLC1A5 (ASCT2) contains two N-glycosylation sites (N163 and N212) located in the large extracellular loop. 25862406 1 7 gly N-glycosylation 161:175 arg2 N163 184:187 N163 184:187 N163 184:187 The human amino acid transporter SLC1A5 (ASCT2) contains two N-glycosylation sites (N163 and N212) located in the large extracellular loop. 25862406 1 7 gly N-glycosylation 161:175 arg2 sites 177:181 two N-glycosylation sites 157:181 two N-glycosylation sites (N163 and N212) located in the large extracellular loop 157:237 The human amino acid transporter SLC1A5 (ASCT2) contains two N-glycosylation sites (N163 and N212) located in the large extracellular loop. 25862406 1 7 gly N-glycosylation 161:175 arg2 two 157:159 two 157:159 two 157:159 The human amino acid transporter SLC1A5 (ASCT2) contains two N-glycosylation sites (N163 and N212) located in the large extracellular loop. 25862406 2 8 theme homology 247:254 arg1 model 267:271 the homology structural model 243:271 the homology structural model of ASCT2 243:280 In the homology structural model of ASCT2 these Asn residues are extracellularly exposed. 25862406 14 9 theme lower 1485:1489 arg1 stability 1491:1499 a slightly or significantly lower stability 1457:1499 a slightly or significantly lower stability with respect to WT 1457:1518 N163Q or N163/212Q showed a slightly or significantly lower stability with respect to WT. 25862406 1 10 theme extracellular 220:232 arg1 loop 234:237 the large extracellular loop 210:237 the large extracellular loop 210:237 The human amino acid transporter SLC1A5 (ASCT2) contains two N-glycosylation sites (N163 and N212) located in the large extracellular loop. 25862406 4 11 theme molecular 452:460 arg1 masses 462:467 apparent molecular masses 443:467 apparent molecular masses from 80kDa to 50kDa 443:487 N163Q and N212Q displayed multiple bands with apparent molecular masses from 80kDa to 50kDa. 25862406 11 12 theme biotinylation 1273:1285 arg1 strategy 1287:1294 a reversible biotinylation strategy 1260:1294 a reversible biotinylation strategy 1260:1294 The rate of endocytosis of ASCT2 was assayed by a reversible biotinylation strategy. 25862406 16 13 theme plasma 1707:1712 arg1 membrane 1714:1721 the plasma membrane 1703:1721 the plasma membrane 1703:1721 One hour after brefeldin removal WT protein was localized to the plasma membrane while the double mutant was localized in the cytosol. 25862406 5 14 gly unglycosylated 554:567 arg1 protein 569:575 the unglycosylated protein 550:575 the unglycosylated protein 550:575 N163/212Q displayed a single band of 50kDa corresponding to the unglycosylated protein. 25862406 4 15 theme apparent 443:450 arg1 masses 462:467 apparent molecular masses 443:467 apparent molecular masses from 80kDa to 50kDa 443:487 N163Q and N212Q displayed multiple bands with apparent molecular masses from 80kDa to 50kDa. 25862406 16 16 theme brefeldin 1657:1665 arg1 removal 1667:1673 brefeldin removal 1657:1673 brefeldin removal 1657:1673 One hour after brefeldin removal WT protein was localized to the plasma membrane while the double mutant was localized in the cytosol. 25862406 0 17 link N-linked 0:7 arg1 glycosylation 9:21 N-linked glycosylation 0:21 N-linked glycosylation of human SLC1A5 (ASCT2) transporter 0:57 N-linked glycosylation of human SLC1A5 (ASCT2) transporter is critical for trafficking to membrane. 25862406 7 18 theme protein 800:806 arg1 synthesis 808:816 protein synthesis 800:816 protein synthesis 800:816 The double mutation significantly impaired the presence of the protein in membrane, without impairment in protein synthesis. 25862406 3 19 theme altered 363:369 arg1 mobility 387:394 altered electrophoretic mobility 363:394 altered electrophoretic mobility 363:394 Mutants of the two Asn exhibited altered electrophoretic mobility. 25862406 7 20 from impairment 786:795 arg1 synthesis 808:816 protein synthesis 800:816 protein synthesis 800:816 The double mutation significantly impaired the presence of the protein in membrane, without impairment in protein synthesis. 25862406 3 21 theme Asn 349:351 arg1 Mutants 330:336 Mutants 330:336 Mutants of the two Asn 330:351 Mutants of the two Asn exhibited altered electrophoretic mobility. 25862406 10 22 theme transport 1160:1168 arg1 function 1170:1177 the intrinsic transport function 1146:1177 the intrinsic transport function of the mutants 1146:1192 The same proteins extracted from cells and reconstituted in liposomes showed comparable transport activities demonstrating that the intrinsic transport function of the mutants was not affected. 25862406 11 23 theme reversible 1262:1271 arg1 strategy 1287:1294 a reversible biotinylation strategy 1260:1294 a reversible biotinylation strategy 1260:1294 The rate of endocytosis of ASCT2 was assayed by a reversible biotinylation strategy. 25862406 16 24 theme hour 1646:1649 arg1 protein 1678:1684 One hour after brefeldin removal WT protein 1642:1684 One hour after brefeldin removal WT protein 1642:1684 One hour after brefeldin removal WT protein was localized to the plasma membrane while the double mutant was localized in the cytosol. 25862406 2 25 theme ASCT2 276:280 arg1 model 267:271 the homology structural model 243:271 the homology structural model of ASCT2 243:280 In the homology structural model of ASCT2 these Asn residues are extracellularly exposed. 25862406 10 26 theme comparable 1095:1104 arg1 activities 1116:1125 comparable transport activities 1095:1125 comparable transport activities demonstrating that the intrinsic transport function of the mutants was not affected 1095:1209 The same proteins extracted from cells and reconstituted in liposomes showed comparable transport activities demonstrating that the intrinsic transport function of the mutants was not affected. 25862406 0 27 theme N-linked 0:7 arg1 glycosylation 9:21 N-linked glycosylation 0:21 N-linked glycosylation of human SLC1A5 (ASCT2) transporter 0:57 N-linked glycosylation of human SLC1A5 (ASCT2) transporter is critical for trafficking to membrane. 25862406 5 28 theme unglycosylated 554:567 arg1 protein 569:575 the unglycosylated protein 550:575 the unglycosylated protein 550:575 N163/212Q displayed a single band of 50kDa corresponding to the unglycosylated protein. 25862406 1 29 theme N-glycosylation 161:175 arg1 N212 193:196 N212 193:196 N212 193:196 The human amino acid transporter SLC1A5 (ASCT2) contains two N-glycosylation sites (N163 and N212) located in the large extracellular loop. 25862406 1 29 theme N-glycosylation 161:175 arg1 N163 184:187 N163 184:187 N163 184:187 The human amino acid transporter SLC1A5 (ASCT2) contains two N-glycosylation sites (N163 and N212) located in the large extracellular loop. 25862406 1 29 theme N-glycosylation 161:175 arg1 sites 177:181 two N-glycosylation sites 157:181 two N-glycosylation sites (N163 and N212) located in the large extracellular loop 157:237 The human amino acid transporter SLC1A5 (ASCT2) contains two N-glycosylation sites (N163 and N212) located in the large extracellular loop. 25862406 0 30 theme human 26:30 arg1 transporter 47:57 human SLC1A5 (ASCT2) transporter 26:57 human SLC1A5 (ASCT2) transporter 26:57 N-linked glycosylation of human SLC1A5 (ASCT2) transporter is critical for trafficking to membrane. 25862406 7 31 attach presence 741:748 arg1 membrane 768:775 membrane 768:775 membrane 768:775 The double mutation significantly impaired the presence of the protein in membrane, without impairment in protein synthesis. 25862406 7 31 attach presence 741:748 arg2 protein 757:763 the protein 753:763 the protein 753:763 The double mutation significantly impaired the presence of the protein in membrane, without impairment in protein synthesis. 25862406 10 32 theme mutants 1186:1192 arg1 function 1170:1177 the intrinsic transport function 1146:1177 the intrinsic transport function of the mutants 1146:1192 The same proteins extracted from cells and reconstituted in liposomes showed comparable transport activities demonstrating that the intrinsic transport function of the mutants was not affected. 25862406 9 33 theme transport 954:962 arg1 activity 964:971 a strongly reduced transport activity 935:971 a strongly reduced transport activity correlating with reduced surface expression 935:1015 N163/212Q exhibited a strongly reduced transport activity correlating with reduced surface expression. 25862406 1 34 from loop 234:237 arg1 located 199:205 located 199:205 located 199:205 The human amino acid transporter SLC1A5 (ASCT2) contains two N-glycosylation sites (N163 and N212) located in the large extracellular loop. 25862406 4 35 theme multiple 423:430 arg1 bands 432:436 multiple bands 423:436 multiple bands 423:436 N163Q and N212Q displayed multiple bands with apparent molecular masses from 80kDa to 50kDa. 25862406 2 36 theme structural 256:265 arg1 model 267:271 the homology structural model 243:271 the homology structural model of ASCT2 243:280 In the homology structural model of ASCT2 these Asn residues are extracellularly exposed. 25862406 6 37 theme biotinylation 646:658 arg1 assay 660:664 protein biotinylation assay 638:664 protein biotinylation assay followed by immunoblotting 638:691 The presence in membrane of WT and mutants was evaluated by protein biotinylation assay followed by immunoblotting. 25862406 3 38 theme electrophoretic 371:385 arg1 mobility 387:394 altered electrophoretic mobility 363:394 altered electrophoretic mobility 363:394 Mutants of the two Asn exhibited altered electrophoretic mobility. 25862406 8 39 theme glutamine 825:833 arg1 H 823:823 3)H 821:823 3)H 821:823 [(3)H]glutamine transport was measured in cells transiently transfected with the WT or mutants. 25862406 8 39 theme glutamine 825:833 arg1 transport 835:843 [(3)H]glutamine transport 819:843 [(3)H]glutamine transport 819:843 [(3)H]glutamine transport was measured in cells transiently transfected with the WT or mutants. 25862406 15 40 theme brefeldin-based 1562:1576 arg1 assay 1578:1582 a brefeldin-based assay 1560:1582 a brefeldin-based assay 1560:1582 To assess trafficking to the membrane, a brefeldin-based assay, which caused retention of proteins in ER, was performed. 25862406 12 41 theme respect 1364:1370 arg1 rates 1343:1347 strongly increased rates 1324:1347 strongly increased rates of endocytosis respect to WT 1324:1376 N212Q and N163/212Q showed strongly increased rates of endocytosis respect to WT. 25862406 6 42 theme protein 638:644 arg1 assay 660:664 protein biotinylation assay 638:664 protein biotinylation assay followed by immunoblotting 638:691 The presence in membrane of WT and mutants was evaluated by protein biotinylation assay followed by immunoblotting. 25862406 0 43 theme SLC1A5 32:37 arg1 transporter 47:57 human SLC1A5 (ASCT2) transporter 26:57 human SLC1A5 (ASCT2) transporter 26:57 N-linked glycosylation of human SLC1A5 (ASCT2) transporter is critical for trafficking to membrane. 25862406 10 44 theme transport 1106:1114 arg1 activities 1116:1125 comparable transport activities 1095:1125 comparable transport activities demonstrating that the intrinsic transport function of the mutants was not affected 1095:1209 The same proteins extracted from cells and reconstituted in liposomes showed comparable transport activities demonstrating that the intrinsic transport function of the mutants was not affected. 25862406 11 45 theme endocytosis 1224:1234 arg1 rate 1216:1219 The rate 1212:1219 The rate of endocytosis of ASCT2 1212:1243 The rate of endocytosis of ASCT2 was assayed by a reversible biotinylation strategy. 25862406 1 46 contain contains 148:155 arg2 N212 193:196 N212 193:196 N212 193:196 The human amino acid transporter SLC1A5 (ASCT2) contains two N-glycosylation sites (N163 and N212) located in the large extracellular loop. 25862406 1 46 contain contains 148:155 arg2 N163 184:187 N163 184:187 N163 184:187 The human amino acid transporter SLC1A5 (ASCT2) contains two N-glycosylation sites (N163 and N212) located in the large extracellular loop. 25862406 1 46 contain contains 148:155 arg2 sites 177:181 two N-glycosylation sites 157:181 two N-glycosylation sites (N163 and N212) located in the large extracellular loop 157:237 The human amino acid transporter SLC1A5 (ASCT2) contains two N-glycosylation sites (N163 and N212) located in the large extracellular loop. 25862406 1 46 contain contains 148:155 arg1 transporter 121:131 The human amino acid transporter SLC1A5 100:138 The human amino acid transporter SLC1A5 (ASCT2) 100:146 The human amino acid transporter SLC1A5 (ASCT2) contains two N-glycosylation sites (N163 and N212) located in the large extracellular loop. 25862406 1 46 contain contains 148:155 arg1 ASCT2 141:145 ASCT2 141:145 ASCT2 141:145 The human amino acid transporter SLC1A5 (ASCT2) contains two N-glycosylation sites (N163 and N212) located in the large extracellular loop. 25862406 0 47 gly glycosylation 9:21 arg1 transporter 47:57 human SLC1A5 (ASCT2) transporter 26:57 human SLC1A5 (ASCT2) transporter 26:57 N-linked glycosylation of human SLC1A5 (ASCT2) transporter is critical for trafficking to membrane. 25862406 4 48 dep 50kDa 483:487 arg1 to 480:481 to 480:481 to 480:481 N163Q and N212Q displayed multiple bands with apparent molecular masses from 80kDa to 50kDa. 25862406 1 49 from located 199:205 arg1 loop 234:237 the large extracellular loop 210:237 the large extracellular loop 210:237 The human amino acid transporter SLC1A5 (ASCT2) contains two N-glycosylation sites (N163 and N212) located in the large extracellular loop. 25862406 6 50 from presence 582:589 arg1 membrane 594:601 membrane 594:601 membrane of WT and mutants 594:619 The presence in membrane of WT and mutants was evaluated by protein biotinylation assay followed by immunoblotting. 25862406 8 51 dep H 823:823 arg1 3 821:821 3 821:821 3 821:821 [(3)H]glutamine transport was measured in cells transiently transfected with the WT or mutants. 25862406 0 52 theme ASCT2 40:44 arg1 transporter 47:57 human SLC1A5 (ASCT2) transporter 26:57 human SLC1A5 (ASCT2) transporter 26:57 N-linked glycosylation of human SLC1A5 (ASCT2) transporter is critical for trafficking to membrane. 25862406 7 53 theme protein 757:763 arg1 presence 741:748 the presence 737:748 the presence of the protein in membrane 737:775 The double mutation significantly impaired the presence of the protein in membrane, without impairment in protein synthesis. 25862406 7 54 from presence 741:748 arg1 membrane 768:775 membrane 768:775 membrane 768:775 The double mutation significantly impaired the presence of the protein in membrane, without impairment in protein synthesis. 25862406 5 55 theme 50kDa 527:531 arg1 band 519:522 a single band 510:522 a single band of 50kDa corresponding to the unglycosylated protein 510:575 N163/212Q displayed a single band of 50kDa corresponding to the unglycosylated protein. 25862406 1 56 theme human 104:108 arg1 transporter 121:131 The human amino acid transporter SLC1A5 100:138 The human amino acid transporter SLC1A5 (ASCT2) 100:146 The human amino acid transporter SLC1A5 (ASCT2) contains two N-glycosylation sites (N163 and N212) located in the large extracellular loop. 25862406 1 56 theme human 104:108 arg1 ASCT2 141:145 ASCT2 141:145 ASCT2 141:145 The human amino acid transporter SLC1A5 (ASCT2) contains two N-glycosylation sites (N163 and N212) located in the large extracellular loop. 25862406 9 57 theme surface 998:1004 arg1 expression 1006:1015 reduced surface expression 990:1015 reduced surface expression 990:1015 N163/212Q exhibited a strongly reduced transport activity correlating with reduced surface expression. 25862406 10 58 theme intrinsic 1150:1158 arg1 function 1170:1177 the intrinsic transport function 1146:1177 the intrinsic transport function of the mutants 1146:1192 The same proteins extracted from cells and reconstituted in liposomes showed comparable transport activities demonstrating that the intrinsic transport function of the mutants was not affected. 25862406 12 59 theme increased 1333:1341 arg1 rates 1343:1347 strongly increased rates 1324:1347 strongly increased rates of endocytosis respect to WT 1324:1376 N212Q and N163/212Q showed strongly increased rates of endocytosis respect to WT. 25862406 12 60 theme endocytosis 1352:1362 arg1 respect 1364:1370 endocytosis respect 1352:1370 endocytosis respect to WT 1352:1376 N212Q and N163/212Q showed strongly increased rates of endocytosis respect to WT. 25862406 1 61 theme amino 110:114 arg1 transporter 121:131 The human amino acid transporter SLC1A5 100:138 The human amino acid transporter SLC1A5 (ASCT2) 100:146 The human amino acid transporter SLC1A5 (ASCT2) contains two N-glycosylation sites (N163 and N212) located in the large extracellular loop. 25862406 1 61 theme amino 110:114 arg1 ASCT2 141:145 ASCT2 141:145 ASCT2 141:145 The human amino acid transporter SLC1A5 (ASCT2) contains two N-glycosylation sites (N163 and N212) located in the large extracellular loop. 25862406 10 62 dep proteins 1027:1034 arg1 reconstituted 1061:1073 reconstituted 1061:1073 reconstituted in liposomes 1061:1086 The same proteins extracted from cells and reconstituted in liposomes showed comparable transport activities demonstrating that the intrinsic transport function of the mutants was not affected. 25862406 10 62 dep proteins 1027:1034 arg1 extracted 1036:1044 extracted 1036:1044 extracted from cells 1036:1055 The same proteins extracted from cells and reconstituted in liposomes showed comparable transport activities demonstrating that the intrinsic transport function of the mutants was not affected. 25862406 9 63 theme reduced 990:996 arg1 expression 1006:1015 reduced surface expression 990:1015 reduced surface expression 990:1015 N163/212Q exhibited a strongly reduced transport activity correlating with reduced surface expression. 25862406 1 64 theme acid 116:119 arg1 transporter 121:131 The human amino acid transporter SLC1A5 100:138 The human amino acid transporter SLC1A5 (ASCT2) 100:146 The human amino acid transporter SLC1A5 (ASCT2) contains two N-glycosylation sites (N163 and N212) located in the large extracellular loop. 25862406 1 64 theme acid 116:119 arg1 ASCT2 141:145 ASCT2 141:145 ASCT2 141:145 The human amino acid transporter SLC1A5 (ASCT2) contains two N-glycosylation sites (N163 and N212) located in the large extracellular loop. 25862406 2 65 theme Asn 288:290 arg1 residues 292:299 these Asn residues 282:299 these Asn residues 282:299 In the homology structural model of ASCT2 these Asn residues are extracellularly exposed. 25862406 10 66 theme same 1022:1025 arg1 proteins 1027:1034 The same proteins 1018:1034 The same proteins extracted from cells and reconstituted in liposomes 1018:1086 The same proteins extracted from cells and reconstituted in liposomes showed comparable transport activities demonstrating that the intrinsic transport function of the mutants was not affected. 25862406 1 67 dep sites 177:181 arg1 N212 193:196 N212 193:196 N212 193:196 The human amino acid transporter SLC1A5 (ASCT2) contains two N-glycosylation sites (N163 and N212) located in the large extracellular loop. 25862406 1 67 dep sites 177:181 arg1 N163 184:187 N163 184:187 N163 184:187 The human amino acid transporter SLC1A5 (ASCT2) contains two N-glycosylation sites (N163 and N212) located in the large extracellular loop. 25862406 1 67 dep sites 177:181 arg1 sites 177:181 two N-glycosylation sites 157:181 two N-glycosylation sites (N163 and N212) located in the large extracellular loop 157:237 The human amino acid transporter SLC1A5 (ASCT2) contains two N-glycosylation sites (N163 and N212) located in the large extracellular loop. 25862406 7 68 theme double 698:703 arg1 mutation 705:712 The double mutation 694:712 The double mutation 694:712 The double mutation significantly impaired the presence of the protein in membrane, without impairment in protein synthesis. 25862406 6 69 theme mutants 613:619 arg1 membrane 594:601 membrane 594:601 membrane of WT and mutants 594:619 The presence in membrane of WT and mutants was evaluated by protein biotinylation assay followed by immunoblotting. 25862406 1 70 theme located 199:205 arg1 N212 193:196 N212 193:196 N212 193:196 The human amino acid transporter SLC1A5 (ASCT2) contains two N-glycosylation sites (N163 and N212) located in the large extracellular loop. 25862406 1 70 theme located 199:205 arg1 N163 184:187 N163 184:187 N163 184:187 The human amino acid transporter SLC1A5 (ASCT2) contains two N-glycosylation sites (N163 and N212) located in the large extracellular loop. 25862406 1 70 theme located 199:205 arg1 sites 177:181 two N-glycosylation sites 157:181 two N-glycosylation sites (N163 and N212) located in the large extracellular loop 157:237 The human amino acid transporter SLC1A5 (ASCT2) contains two N-glycosylation sites (N163 and N212) located in the large extracellular loop. 25862406 0 71 theme transporter 47:57 arg1 glycosylation 9:21 N-linked glycosylation 0:21 N-linked glycosylation of human SLC1A5 (ASCT2) transporter 0:57 N-linked glycosylation of human SLC1A5 (ASCT2) transporter is critical for trafficking to membrane. 25862406 15 72 theme proteins 1611:1618 arg1 retention 1598:1606 retention 1598:1606 retention of proteins 1598:1618 To assess trafficking to the membrane, a brefeldin-based assay, which caused retention of proteins in ER, was performed. 25862406 16 73 located localized 1751:1759 arg1 cytosol 1768:1774 the cytosol 1764:1774 the cytosol 1764:1774 One hour after brefeldin removal WT protein was localized to the plasma membrane while the double mutant was localized in the cytosol. 25862406 16 73 located localized 1751:1759 arg2 mutant 1740:1745 the double mutant 1729:1745 the double mutant 1729:1745 One hour after brefeldin removal WT protein was localized to the plasma membrane while the double mutant was localized in the cytosol. 25862406 16 74 theme double 1733:1738 arg1 mutant 1740:1745 the double mutant 1729:1745 the double mutant 1729:1745 One hour after brefeldin removal WT protein was localized to the plasma membrane while the double mutant was localized in the cytosol. 25862406 13 75 theme ASCT2 1379:1383 arg1 stability 1385:1393 ASCT2 stability 1379:1393 ASCT2 stability 1379:1393 ASCT2 stability was determined using cycloheximide. 25835533 5 0 theme vGPCR 616:620 arg1 mutants 622:628 vGPCR mutants 616:628 vGPCR mutants whose glycosylation sites were ablated 616:667 Employing vGPCR mutants whose glycosylation sites were ablated, we show that these vGPCR mutants failed to activate downstream signaling in cultured cells and were severely impaired to induce tumor formation in the xenograph nude mouse model. 25835533 6 1 gly glycosylation 892:904 arg1 vGPCR 922:926 vGPCR tumorigenesis 922:940 vGPCR tumorigenesis 922:940 These findings support the conclusion that glycosylation is critical for vGPCR tumorigenesis and imply that chemokine regulation at the plasma membrane is crucial for vGPCR mediated signaling. 25835533 2 2 theme KHSV 303:306 arg1 infection 308:316 KHSV infection 303:316 KHSV infection 303:316 KSHV G protein-coupled receptor (vGPCR) is an oncogene that is implicated in malignancies associated with KHSV infection. 25835533 6 3 from membrane 992:999 arg1 regulation 967:976 chemokine regulation 957:976 chemokine regulation at the plasma membrane 957:999 These findings support the conclusion that glycosylation is critical for vGPCR tumorigenesis and imply that chemokine regulation at the plasma membrane is crucial for vGPCR mediated signaling. 25835533 5 4 theme vGPCR 689:693 arg1 mutants 695:701 these vGPCR mutants 683:701 these vGPCR mutants 683:701 Employing vGPCR mutants whose glycosylation sites were ablated, we show that these vGPCR mutants failed to activate downstream signaling in cultured cells and were severely impaired to induce tumor formation in the xenograph nude mouse model. 25835533 5 5 theme glycosylation 636:648 arg1 sites 650:654 glycosylation sites 636:654 glycosylation sites 636:654 Employing vGPCR mutants whose glycosylation sites were ablated, we show that these vGPCR mutants failed to activate downstream signaling in cultured cells and were severely impaired to induce tumor formation in the xenograph nude mouse model. 25835533 6 6 theme chemokine 957:965 arg1 regulation 967:976 chemokine regulation 957:976 chemokine regulation at the plasma membrane 957:999 These findings support the conclusion that glycosylation is critical for vGPCR tumorigenesis and imply that chemokine regulation at the plasma membrane is crucial for vGPCR mediated signaling. 25835533 6 7 theme mediated 1022:1029 arg1 signaling 1031:1039 vGPCR mediated signaling 1016:1039 vGPCR mediated signaling 1016:1039 These findings support the conclusion that glycosylation is critical for vGPCR tumorigenesis and imply that chemokine regulation at the plasma membrane is crucial for vGPCR mediated signaling. 25835533 3 8 theme extensive 363:371 arg1 glycosylation 382:394 extensive N-linked glycosylation 363:394 extensive N-linked glycosylation 363:394 In this study, we show that vGPCR undergoes extensive N-linked glycosylation within the extracellular domains, specifically asparagines 18, 22, 31 and 202. 25835533 5 9 theme xenograph 821:829 arg1 model 842:846 the xenograph nude mouse model 817:846 the xenograph nude mouse model 817:846 Employing vGPCR mutants whose glycosylation sites were ablated, we show that these vGPCR mutants failed to activate downstream signaling in cultured cells and were severely impaired to induce tumor formation in the xenograph nude mouse model. 25835533 0 10 from functions 36:44 arg1 tumorigenicity 67:80 tumorigenicity 67:80 tumorigenicity 67:80 Glycosylation of KSHV encoded vGPCR functions in its signaling and tumorigenicity. 25835533 0 10 from functions 36:44 arg1 signaling 53:61 signaling 53:61 signaling 53:61 Glycosylation of KSHV encoded vGPCR functions in its signaling and tumorigenicity. 25835533 3 11 link N-linked 373:380 arg1 glycosylation 382:394 extensive N-linked glycosylation 363:394 extensive N-linked glycosylation 363:394 In this study, we show that vGPCR undergoes extensive N-linked glycosylation within the extracellular domains, specifically asparagines 18, 22, 31 and 202. 25835533 1 12 theme etiologic 155:163 arg1 agent 165:169 the etiologic agent 151:169 the etiologic agent of Kaposi's Sarcoma (KS) 151:194 Kaposi's sarcoma-associated herpesvirus (KSHV) is a tumor virus and the etiologic agent of Kaposi's Sarcoma (KS). 25835533 5 13 gly glycosylation 636:648 arg2 sites 650:654 glycosylation sites 636:654 glycosylation sites 636:654 Employing vGPCR mutants whose glycosylation sites were ablated, we show that these vGPCR mutants failed to activate downstream signaling in cultured cells and were severely impaired to induce tumor formation in the xenograph nude mouse model. 25835533 3 14 theme N-linked 373:380 arg1 glycosylation 382:394 extensive N-linked glycosylation 363:394 extensive N-linked glycosylation 363:394 In this study, we show that vGPCR undergoes extensive N-linked glycosylation within the extracellular domains, specifically asparagines 18, 22, 31 and 202. 25835533 1 15 theme sarcoma-associated 92:109 arg1 virus 141:145 a tumor virus 133:145 a tumor virus 133:145 Kaposi's sarcoma-associated herpesvirus (KSHV) is a tumor virus and the etiologic agent of Kaposi's Sarcoma (KS). 25835533 1 15 theme sarcoma-associated 92:109 arg1 KSHV 124:127 KSHV 124:127 KSHV 124:127 Kaposi's sarcoma-associated herpesvirus (KSHV) is a tumor virus and the etiologic agent of Kaposi's Sarcoma (KS). 25835533 1 15 theme sarcoma-associated 92:109 arg1 herpesvirus 111:121 Kaposi's sarcoma-associated herpesvirus 83:121 Kaposi's sarcoma-associated herpesvirus (KSHV) 83:128 Kaposi's sarcoma-associated herpesvirus (KSHV) is a tumor virus and the etiologic agent of Kaposi's Sarcoma (KS). 25835533 5 16 theme tumor 798:802 arg1 formation 804:812 tumor formation 798:812 tumor formation 798:812 Employing vGPCR mutants whose glycosylation sites were ablated, we show that these vGPCR mutants failed to activate downstream signaling in cultured cells and were severely impaired to induce tumor formation in the xenograph nude mouse model. 25835533 0 17 theme KSHV 17:20 arg1 functions 36:44 vGPCR functions 30:44 vGPCR functions in its signaling and tumorigenicity 30:80 Glycosylation of KSHV encoded vGPCR functions in its signaling and tumorigenicity. 25835533 0 17 theme KSHV 17:20 arg1 Glycosylation 0:12 Glycosylation 0:12 Glycosylation of KSHV 0:20 Glycosylation of KSHV encoded vGPCR functions in its signaling and tumorigenicity. 25835533 4 18 theme N-linked 521:528 arg1 glycosylation 530:542 N-linked glycosylation 521:542 N-linked glycosylation 521:542 An immunofluorescence assay demonstrates that N-linked glycosylation are necessary for vGPCR trafficking to the cellular membrane. 25835533 4 19 theme cellular 587:594 arg1 membrane 596:603 the cellular membrane 583:603 the cellular membrane 583:603 An immunofluorescence assay demonstrates that N-linked glycosylation are necessary for vGPCR trafficking to the cellular membrane. 25835533 5 20 theme cultured 746:753 arg1 cells 755:759 cultured cells 746:759 cultured cells 746:759 Employing vGPCR mutants whose glycosylation sites were ablated, we show that these vGPCR mutants failed to activate downstream signaling in cultured cells and were severely impaired to induce tumor formation in the xenograph nude mouse model. 25835533 0 21 gly Glycosylation 0:12 arg1 KSHV 17:20 KSHV 17:20 KSHV 17:20 Glycosylation of KSHV encoded vGPCR functions in its signaling and tumorigenicity. 25835533 1 22 theme Sarcoma 183:189 arg1 agent 165:169 the etiologic agent 151:169 the etiologic agent of Kaposi's Sarcoma (KS) 151:194 Kaposi's sarcoma-associated herpesvirus (KSHV) is a tumor virus and the etiologic agent of Kaposi's Sarcoma (KS). 25835533 1 22 theme Sarcoma 183:189 arg1 virus 141:145 a tumor virus 133:145 a tumor virus 133:145 Kaposi's sarcoma-associated herpesvirus (KSHV) is a tumor virus and the etiologic agent of Kaposi's Sarcoma (KS). 25835533 1 22 theme Sarcoma 183:189 arg1 herpesvirus 111:121 Kaposi's sarcoma-associated herpesvirus 83:121 Kaposi's sarcoma-associated herpesvirus (KSHV) 83:128 Kaposi's sarcoma-associated herpesvirus (KSHV) is a tumor virus and the etiologic agent of Kaposi's Sarcoma (KS). 25835533 0 23 theme vGPCR 30:34 arg1 functions 36:44 vGPCR functions 30:44 vGPCR functions in its signaling and tumorigenicity 30:80 Glycosylation of KSHV encoded vGPCR functions in its signaling and tumorigenicity. 25835533 0 23 theme vGPCR 30:34 arg1 Glycosylation 0:12 Glycosylation 0:12 Glycosylation of KSHV 0:20 Glycosylation of KSHV encoded vGPCR functions in its signaling and tumorigenicity. 25835533 6 24 theme vGPCR 922:926 arg1 tumorigenesis 928:940 vGPCR tumorigenesis 922:940 vGPCR tumorigenesis 922:940 These findings support the conclusion that glycosylation is critical for vGPCR tumorigenesis and imply that chemokine regulation at the plasma membrane is crucial for vGPCR mediated signaling. 25835533 5 25 theme mouse 836:840 arg1 model 842:846 the xenograph nude mouse model 817:846 the xenograph nude mouse model 817:846 Employing vGPCR mutants whose glycosylation sites were ablated, we show that these vGPCR mutants failed to activate downstream signaling in cultured cells and were severely impaired to induce tumor formation in the xenograph nude mouse model. 25835533 3 26 theme extracellular 407:419 arg1 domains 421:427 the extracellular domains 403:427 the extracellular domains 403:427 In this study, we show that vGPCR undergoes extensive N-linked glycosylation within the extracellular domains, specifically asparagines 18, 22, 31 and 202. 25835533 4 27 theme immunofluorescence 478:495 arg1 assay 497:501 An immunofluorescence assay 475:501 An immunofluorescence assay 475:501 An immunofluorescence assay demonstrates that N-linked glycosylation are necessary for vGPCR trafficking to the cellular membrane. 25835533 5 28 from signaling 733:741 arg1 cells 755:759 cultured cells 746:759 cultured cells 746:759 Employing vGPCR mutants whose glycosylation sites were ablated, we show that these vGPCR mutants failed to activate downstream signaling in cultured cells and were severely impaired to induce tumor formation in the xenograph nude mouse model. 25835533 3 29 gly glycosylation 382:394 arg1 vGPCR 347:351 vGPCR 347:351 vGPCR 347:351 In this study, we show that vGPCR undergoes extensive N-linked glycosylation within the extracellular domains, specifically asparagines 18, 22, 31 and 202. 25835533 4 30 theme vGPCR 562:566 arg1 trafficking 568:578 vGPCR trafficking 562:578 vGPCR trafficking to the cellular membrane 562:603 An immunofluorescence assay demonstrates that N-linked glycosylation are necessary for vGPCR trafficking to the cellular membrane. 25835533 2 31 theme protein-coupled 204:218 arg1 vGPCR 230:234 vGPCR 230:234 vGPCR 230:234 KSHV G protein-coupled receptor (vGPCR) is an oncogene that is implicated in malignancies associated with KHSV infection. 25835533 2 31 theme protein-coupled 204:218 arg1 receptor 220:227 KSHV G protein-coupled receptor 197:227 KSHV G protein-coupled receptor (vGPCR) 197:235 KSHV G protein-coupled receptor (vGPCR) is an oncogene that is implicated in malignancies associated with KHSV infection. 25835533 2 31 theme protein-coupled 204:218 arg1 oncogene 243:250 an oncogene 240:250 an oncogene that is implicated in malignancies associated with KHSV infection 240:316 KSHV G protein-coupled receptor (vGPCR) is an oncogene that is implicated in malignancies associated with KHSV infection. 25835533 5 32 theme nude 831:834 arg1 model 842:846 the xenograph nude mouse model 817:846 the xenograph nude mouse model 817:846 Employing vGPCR mutants whose glycosylation sites were ablated, we show that these vGPCR mutants failed to activate downstream signaling in cultured cells and were severely impaired to induce tumor formation in the xenograph nude mouse model. 25835533 5 33 theme downstream 722:731 arg1 signaling 733:741 downstream signaling 722:741 downstream signaling in cultured cells 722:759 Employing vGPCR mutants whose glycosylation sites were ablated, we show that these vGPCR mutants failed to activate downstream signaling in cultured cells and were severely impaired to induce tumor formation in the xenograph nude mouse model. 25835533 4 34 link N-linked 521:528 arg1 glycosylation 530:542 N-linked glycosylation 521:542 N-linked glycosylation 521:542 An immunofluorescence assay demonstrates that N-linked glycosylation are necessary for vGPCR trafficking to the cellular membrane. 25835533 1 35 theme tumor 135:139 arg1 virus 141:145 a tumor virus 133:145 a tumor virus 133:145 Kaposi's sarcoma-associated herpesvirus (KSHV) is a tumor virus and the etiologic agent of Kaposi's Sarcoma (KS). 25835533 1 35 theme tumor 135:139 arg1 herpesvirus 111:121 Kaposi's sarcoma-associated herpesvirus 83:121 Kaposi's sarcoma-associated herpesvirus (KSHV) 83:128 Kaposi's sarcoma-associated herpesvirus (KSHV) is a tumor virus and the etiologic agent of Kaposi's Sarcoma (KS). 25835533 6 36 theme plasma 985:990 arg1 membrane 992:999 the plasma membrane 981:999 the plasma membrane 981:999 These findings support the conclusion that glycosylation is critical for vGPCR tumorigenesis and imply that chemokine regulation at the plasma membrane is crucial for vGPCR mediated signaling. 27539975 4 0 theme studied 876:882 arg1 mammals 884:890 the other studied mammals 866:890 the other studied mammals 866:890 Most glycosylation sites in humans were classified as known and those in the other studied mammals as unknown, according to Swiss-Prot annotations. 27539975 7 1 from milk 1316:1319 arg1 number 1271:1276 the number 1267:1276 the number of known N-glycosylation sites in the milk from dairy animal species 1267:1345 The findings increased the number of known N-glycosylation sites in the milk from dairy animal species, revealed the complexity of the MFGM glycoproteome, and provided useful information to further explore the mechanism of MFGM glycoproteins biosynthesis among the studied mammals. 27539975 6 2 theme Holstein 1110:1117 arg1 cows 1130:1133 Holstein and Jersey cows 1110:1133 Holstein and Jersey cows 1110:1133 N-glycosylated protein components of MFGM fractions from Holstein and Jersey cows, buffaloes, yaks, and goats were more similar to each other compared with those of camels, horses and human. 27539975 2 3 dep Holstein 593:600 arg1 goats 636:640 goats 636:640 goats 636:640 N-linked glycosylation sites and glycoproteins in milk fat globule membrane (MFGM) fractions were investigated by combining N-glycosylated peptides enrichment and high-accuracy Q Exactive identification, to map the N-glycoproteome profiles in Holstein and Jersey cows, buffaloes, yaks, goats, camels, horses, and humans. 27539975 2 3 dep Holstein 593:600 arg1 humans 663:668 humans 663:668 humans 663:668 N-linked glycosylation sites and glycoproteins in milk fat globule membrane (MFGM) fractions were investigated by combining N-glycosylated peptides enrichment and high-accuracy Q Exactive identification, to map the N-glycoproteome profiles in Holstein and Jersey cows, buffaloes, yaks, goats, camels, horses, and humans. 27539975 2 3 dep Holstein 593:600 arg1 cows 613:616 cows 613:616 cows 613:616 N-linked glycosylation sites and glycoproteins in milk fat globule membrane (MFGM) fractions were investigated by combining N-glycosylated peptides enrichment and high-accuracy Q Exactive identification, to map the N-glycoproteome profiles in Holstein and Jersey cows, buffaloes, yaks, goats, camels, horses, and humans. 27539975 2 3 dep Holstein 593:600 arg1 buffaloes 619:627 buffaloes 619:627 buffaloes 619:627 N-linked glycosylation sites and glycoproteins in milk fat globule membrane (MFGM) fractions were investigated by combining N-glycosylated peptides enrichment and high-accuracy Q Exactive identification, to map the N-glycoproteome profiles in Holstein and Jersey cows, buffaloes, yaks, goats, camels, horses, and humans. 27539975 2 3 dep Holstein 593:600 arg1 camels 643:648 camels 643:648 camels 643:648 N-linked glycosylation sites and glycoproteins in milk fat globule membrane (MFGM) fractions were investigated by combining N-glycosylated peptides enrichment and high-accuracy Q Exactive identification, to map the N-glycoproteome profiles in Holstein and Jersey cows, buffaloes, yaks, goats, camels, horses, and humans. 27539975 2 3 dep Holstein 593:600 arg1 horses 651:656 horses 651:656 horses 651:656 N-linked glycosylation sites and glycoproteins in milk fat globule membrane (MFGM) fractions were investigated by combining N-glycosylated peptides enrichment and high-accuracy Q Exactive identification, to map the N-glycoproteome profiles in Holstein and Jersey cows, buffaloes, yaks, goats, camels, horses, and humans. 27539975 2 3 dep Holstein 593:600 arg1 yaks 630:633 yaks 630:633 yaks 630:633 N-linked glycosylation sites and glycoproteins in milk fat globule membrane (MFGM) fractions were investigated by combining N-glycosylated peptides enrichment and high-accuracy Q Exactive identification, to map the N-glycoproteome profiles in Holstein and Jersey cows, buffaloes, yaks, goats, camels, horses, and humans. 27539975 2 4 from sites 373:377 arg1 fractions 433:441 milk fat globule membrane (MFGM) fractions 400:441 milk fat globule membrane (MFGM) fractions 400:441 N-linked glycosylation sites and glycoproteins in milk fat globule membrane (MFGM) fractions were investigated by combining N-glycosylated peptides enrichment and high-accuracy Q Exactive identification, to map the N-glycoproteome profiles in Holstein and Jersey cows, buffaloes, yaks, goats, camels, horses, and humans. 27539975 2 5 from glycoproteins 383:395 arg1 fractions 433:441 milk fat globule membrane (MFGM) fractions 400:441 milk fat globule membrane (MFGM) fractions 400:441 N-linked glycosylation sites and glycoproteins in milk fat globule membrane (MFGM) fractions were investigated by combining N-glycosylated peptides enrichment and high-accuracy Q Exactive identification, to map the N-glycoproteome profiles in Holstein and Jersey cows, buffaloes, yaks, goats, camels, horses, and humans. 27539975 7 6 theme MFGM 1379:1382 arg1 glycoproteome 1384:1396 the MFGM glycoproteome 1375:1396 the MFGM glycoproteome 1375:1396 The findings increased the number of known N-glycosylation sites in the milk from dairy animal species, revealed the complexity of the MFGM glycoproteome, and provided useful information to further explore the mechanism of MFGM glycoproteins biosynthesis among the studied mammals. 27539975 3 7 theme MFGM 754:757 arg1 fractions 759:767 the MFGM fractions 750:767 the MFGM fractions of the studied mammals 750:790 A total of 399 N-glycoproteins with 677 glycosylation sites were identified in the MFGM fractions of the studied mammals. 27539975 3 8 theme studied 776:782 arg1 mammals 784:790 the studied mammals 772:790 the studied mammals 772:790 A total of 399 N-glycoproteins with 677 glycosylation sites were identified in the MFGM fractions of the studied mammals. 27539975 1 9 theme proteins 141:148 arg1 Glycosylation 124:136 Glycosylation 124:136 Glycosylation of proteins 124:148 Glycosylation of proteins has been implicated in various biological functions and has received much attention; however, glycoprotein components and inter-species complexity have not yet been elucidated fully in milk proteins. 27539975 7 10 theme animal 1332:1337 arg1 species 1339:1345 dairy animal species 1326:1345 dairy animal species 1326:1345 The findings increased the number of known N-glycosylation sites in the milk from dairy animal species, revealed the complexity of the MFGM glycoproteome, and provided useful information to further explore the mechanism of MFGM glycoproteins biosynthesis among the studied mammals. 27539975 5 11 gly glycoproteins 978:990 arg1 glycoproteins 978:990 the identified glycoproteins 963:990 the identified glycoproteins 963:990 Functionally, most of the identified glycoproteins were associated with the 'response to stimulus' GO category. 27539975 6 12 theme protein 1068:1074 arg1 components 1076:1085 N-glycosylated protein components 1053:1085 N-glycosylated protein components of MFGM fractions from Holstein and Jersey cows, buffaloes, yaks, and goats 1053:1161 N-glycosylated protein components of MFGM fractions from Holstein and Jersey cows, buffaloes, yaks, and goats were more similar to each other compared with those of camels, horses and human. 27539975 0 13 theme fat 80:82 arg1 proteins 101:108 milk fat globule membrane proteins 75:108 milk fat globule membrane proteins from mammals 75:121 N-glycosylation proteomic characterization and cross-species comparison of milk fat globule membrane proteins from mammals. 27539975 4 14 from sites 812:816 arg1 humans 821:826 humans 821:826 humans 821:826 Most glycosylation sites in humans were classified as known and those in the other studied mammals as unknown, according to Swiss-Prot annotations. 27539975 0 15 from characterization 26:41 arg1 mammals 115:121 mammals 115:121 mammals 115:121 N-glycosylation proteomic characterization and cross-species comparison of milk fat globule membrane proteins from mammals. 27539975 0 16 theme membrane 92:99 arg1 proteins 101:108 milk fat globule membrane proteins 75:108 milk fat globule membrane proteins from mammals 75:121 N-glycosylation proteomic characterization and cross-species comparison of milk fat globule membrane proteins from mammals. 27539975 0 17 from mammals 115:121 arg1 characterization 26:41 N-glycosylation proteomic characterization 0:41 N-glycosylation proteomic characterization 0:41 N-glycosylation proteomic characterization and cross-species comparison of milk fat globule membrane proteins from mammals. 27539975 0 17 from mammals 115:121 arg1 comparison 61:70 cross-species comparison 47:70 cross-species comparison 47:70 N-glycosylation proteomic characterization and cross-species comparison of milk fat globule membrane proteins from mammals. 27539975 0 17 from mammals 115:121 arg1 proteins 101:108 milk fat globule membrane proteins 75:108 milk fat globule membrane proteins from mammals 75:121 N-glycosylation proteomic characterization and cross-species comparison of milk fat globule membrane proteins from mammals. 27539975 1 18 gly glycoprotein 244:255 arg1 glycoprotein 244:255 glycoprotein components 244:266 glycoprotein components 244:266 Glycosylation of proteins has been implicated in various biological functions and has received much attention; however, glycoprotein components and inter-species complexity have not yet been elucidated fully in milk proteins. 27539975 1 19 theme biological 181:190 arg1 functions 192:200 various biological functions 173:200 various biological functions 173:200 Glycosylation of proteins has been implicated in various biological functions and has received much attention; however, glycoprotein components and inter-species complexity have not yet been elucidated fully in milk proteins. 27539975 7 20 theme N-glycosylation 1287:1301 arg1 sites 1303:1307 known N-glycosylation sites 1281:1307 known N-glycosylation sites in the milk from dairy animal species 1281:1345 The findings increased the number of known N-glycosylation sites in the milk from dairy animal species, revealed the complexity of the MFGM glycoproteome, and provided useful information to further explore the mechanism of MFGM glycoproteins biosynthesis among the studied mammals. 27539975 4 21 theme Most 793:796 arg1 sites 812:816 Most glycosylation sites 793:816 Most glycosylation sites in humans 793:826 Most glycosylation sites in humans were classified as known and those in the other studied mammals as unknown, according to Swiss-Prot annotations. 27539975 2 22 theme MFGM 427:430 arg1 fractions 433:441 milk fat globule membrane (MFGM) fractions 400:441 milk fat globule membrane (MFGM) fractions 400:441 N-linked glycosylation sites and glycoproteins in milk fat globule membrane (MFGM) fractions were investigated by combining N-glycosylated peptides enrichment and high-accuracy Q Exactive identification, to map the N-glycoproteome profiles in Holstein and Jersey cows, buffaloes, yaks, goats, camels, horses, and humans. 27539975 6 23 theme MFGM 1090:1093 arg1 fractions 1095:1103 MFGM fractions 1090:1103 MFGM fractions from Holstein and Jersey cows, buffaloes, yaks, and goats 1090:1161 N-glycosylated protein components of MFGM fractions from Holstein and Jersey cows, buffaloes, yaks, and goats were more similar to each other compared with those of camels, horses and human. 27539975 2 24 theme membrane 417:424 arg1 fractions 433:441 milk fat globule membrane (MFGM) fractions 400:441 milk fat globule membrane (MFGM) fractions 400:441 N-linked glycosylation sites and glycoproteins in milk fat globule membrane (MFGM) fractions were investigated by combining N-glycosylated peptides enrichment and high-accuracy Q Exactive identification, to map the N-glycoproteome profiles in Holstein and Jersey cows, buffaloes, yaks, goats, camels, horses, and humans. 27539975 0 25 theme N-glycosylation 0:14 arg1 characterization 26:41 N-glycosylation proteomic characterization 0:41 N-glycosylation proteomic characterization 0:41 N-glycosylation proteomic characterization and cross-species comparison of milk fat globule membrane proteins from mammals. 27539975 6 26 gly N-glycosylated 1053:1066 arg1 components 1076:1085 N-glycosylated protein components 1053:1085 N-glycosylated protein components of MFGM fractions from Holstein and Jersey cows, buffaloes, yaks, and goats 1053:1161 N-glycosylated protein components of MFGM fractions from Holstein and Jersey cows, buffaloes, yaks, and goats were more similar to each other compared with those of camels, horses and human. 27539975 6 27 from yaks 1147:1150 arg1 components 1076:1085 N-glycosylated protein components 1053:1085 N-glycosylated protein components of MFGM fractions from Holstein and Jersey cows, buffaloes, yaks, and goats 1053:1161 N-glycosylated protein components of MFGM fractions from Holstein and Jersey cows, buffaloes, yaks, and goats were more similar to each other compared with those of camels, horses and human. 27539975 6 27 from yaks 1147:1150 arg1 fractions 1095:1103 MFGM fractions 1090:1103 MFGM fractions from Holstein and Jersey cows, buffaloes, yaks, and goats 1090:1161 N-glycosylated protein components of MFGM fractions from Holstein and Jersey cows, buffaloes, yaks, and goats were more similar to each other compared with those of camels, horses and human. 27539975 6 28 theme N-glycosylated 1053:1066 arg1 components 1076:1085 N-glycosylated protein components 1053:1085 N-glycosylated protein components of MFGM fractions from Holstein and Jersey cows, buffaloes, yaks, and goats 1053:1161 N-glycosylated protein components of MFGM fractions from Holstein and Jersey cows, buffaloes, yaks, and goats were more similar to each other compared with those of camels, horses and human. 27539975 2 29 theme Q 527:527 arg1 peptides 489:496 N-glycosylated peptides 474:496 N-glycosylated peptides enrichment and high-accuracy Q Exactive identification 474:551 N-linked glycosylation sites and glycoproteins in milk fat globule membrane (MFGM) fractions were investigated by combining N-glycosylated peptides enrichment and high-accuracy Q Exactive identification, to map the N-glycoproteome profiles in Holstein and Jersey cows, buffaloes, yaks, goats, camels, horses, and humans. 27539975 2 29 theme Q 527:527 arg1 identification 538:551 high-accuracy Q Exactive identification 513:551 high-accuracy Q Exactive identification 513:551 N-linked glycosylation sites and glycoproteins in milk fat globule membrane (MFGM) fractions were investigated by combining N-glycosylated peptides enrichment and high-accuracy Q Exactive identification, to map the N-glycoproteome profiles in Holstein and Jersey cows, buffaloes, yaks, goats, camels, horses, and humans. 27539975 2 30 gly glycoproteins 383:395 arg1 glycoproteins 383:395 glycoproteins 383:395 glycoproteins 383:395 N-linked glycosylation sites and glycoproteins in milk fat globule membrane (MFGM) fractions were investigated by combining N-glycosylated peptides enrichment and high-accuracy Q Exactive identification, to map the N-glycoproteome profiles in Holstein and Jersey cows, buffaloes, yaks, goats, camels, horses, and humans. 27539975 0 31 theme cross-species 47:59 arg1 comparison 61:70 cross-species comparison 47:70 cross-species comparison 47:70 N-glycosylation proteomic characterization and cross-species comparison of milk fat globule membrane proteins from mammals. 27539975 7 32 theme studied 1509:1515 arg1 mammals 1517:1523 the studied mammals 1505:1523 the studied mammals 1505:1523 The findings increased the number of known N-glycosylation sites in the milk from dairy animal species, revealed the complexity of the MFGM glycoproteome, and provided useful information to further explore the mechanism of MFGM glycoproteins biosynthesis among the studied mammals. 27539975 7 33 from number 1271:1276 arg1 milk 1316:1319 the milk 1312:1319 the milk from dairy animal species 1312:1345 The findings increased the number of known N-glycosylation sites in the milk from dairy animal species, revealed the complexity of the MFGM glycoproteome, and provided useful information to further explore the mechanism of MFGM glycoproteins biosynthesis among the studied mammals. 27539975 3 34 gly glycosylation 711:723 arg2 sites 725:729 677 glycosylation sites 707:729 677 glycosylation sites 707:729 A total of 399 N-glycoproteins with 677 glycosylation sites were identified in the MFGM fractions of the studied mammals. 27539975 6 35 from cows 1130:1133 arg1 components 1076:1085 N-glycosylated protein components 1053:1085 N-glycosylated protein components of MFGM fractions from Holstein and Jersey cows, buffaloes, yaks, and goats 1053:1161 N-glycosylated protein components of MFGM fractions from Holstein and Jersey cows, buffaloes, yaks, and goats were more similar to each other compared with those of camels, horses and human. 27539975 6 35 from cows 1130:1133 arg1 fractions 1095:1103 MFGM fractions 1090:1103 MFGM fractions from Holstein and Jersey cows, buffaloes, yaks, and goats 1090:1161 N-glycosylated protein components of MFGM fractions from Holstein and Jersey cows, buffaloes, yaks, and goats were more similar to each other compared with those of camels, horses and human. 27539975 3 36 theme N-glycoproteins 686:700 arg1 total 673:677 A total 671:677 A total of 399 N-glycoproteins with 677 glycosylation sites 671:729 A total of 399 N-glycoproteins with 677 glycosylation sites were identified in the MFGM fractions of the studied mammals. 27539975 6 37 from buffaloes 1136:1144 arg1 components 1076:1085 N-glycosylated protein components 1053:1085 N-glycosylated protein components of MFGM fractions from Holstein and Jersey cows, buffaloes, yaks, and goats 1053:1161 N-glycosylated protein components of MFGM fractions from Holstein and Jersey cows, buffaloes, yaks, and goats were more similar to each other compared with those of camels, horses and human. 27539975 6 37 from buffaloes 1136:1144 arg1 fractions 1095:1103 MFGM fractions 1090:1103 MFGM fractions from Holstein and Jersey cows, buffaloes, yaks, and goats 1090:1161 N-glycosylated protein components of MFGM fractions from Holstein and Jersey cows, buffaloes, yaks, and goats were more similar to each other compared with those of camels, horses and human. 27539975 2 38 theme glycosylation 359:371 arg1 sites 373:377 N-linked glycosylation sites 350:377 N-linked glycosylation sites 350:377 N-linked glycosylation sites and glycoproteins in milk fat globule membrane (MFGM) fractions were investigated by combining N-glycosylated peptides enrichment and high-accuracy Q Exactive identification, to map the N-glycoproteome profiles in Holstein and Jersey cows, buffaloes, yaks, goats, camels, horses, and humans. 27539975 7 39 theme glycoproteins 1472:1484 arg1 biosynthesis 1486:1497 MFGM glycoproteins biosynthesis 1467:1497 MFGM glycoproteins biosynthesis 1467:1497 The findings increased the number of known N-glycosylation sites in the milk from dairy animal species, revealed the complexity of the MFGM glycoproteome, and provided useful information to further explore the mechanism of MFGM glycoproteins biosynthesis among the studied mammals. 27539975 7 40 from sites 1303:1307 arg1 species 1339:1345 dairy animal species 1326:1345 dairy animal species 1326:1345 The findings increased the number of known N-glycosylation sites in the milk from dairy animal species, revealed the complexity of the MFGM glycoproteome, and provided useful information to further explore the mechanism of MFGM glycoproteins biosynthesis among the studied mammals. 27539975 7 40 from sites 1303:1307 arg1 milk 1316:1319 the milk 1312:1319 the milk from dairy animal species 1312:1345 The findings increased the number of known N-glycosylation sites in the milk from dairy animal species, revealed the complexity of the MFGM glycoproteome, and provided useful information to further explore the mechanism of MFGM glycoproteins biosynthesis among the studied mammals. 27539975 2 41 theme fat 405:407 arg1 fractions 433:441 milk fat globule membrane (MFGM) fractions 400:441 milk fat globule membrane (MFGM) fractions 400:441 N-linked glycosylation sites and glycoproteins in milk fat globule membrane (MFGM) fractions were investigated by combining N-glycosylated peptides enrichment and high-accuracy Q Exactive identification, to map the N-glycoproteome profiles in Holstein and Jersey cows, buffaloes, yaks, goats, camels, horses, and humans. 27539975 2 42 link N-linked 350:357 arg1 sites 373:377 N-linked glycosylation sites 350:377 N-linked glycosylation sites 350:377 N-linked glycosylation sites and glycoproteins in milk fat globule membrane (MFGM) fractions were investigated by combining N-glycosylated peptides enrichment and high-accuracy Q Exactive identification, to map the N-glycoproteome profiles in Holstein and Jersey cows, buffaloes, yaks, goats, camels, horses, and humans. 27539975 1 43 theme inter-species 272:284 arg1 complexity 286:295 inter-species complexity 272:295 inter-species complexity 272:295 Glycosylation of proteins has been implicated in various biological functions and has received much attention; however, glycoprotein components and inter-species complexity have not yet been elucidated fully in milk proteins. 27539975 4 44 theme other 870:874 arg1 mammals 884:890 the other studied mammals 866:890 the other studied mammals 866:890 Most glycosylation sites in humans were classified as known and those in the other studied mammals as unknown, according to Swiss-Prot annotations. 27539975 3 45 theme 677 707:709 arg1 sites 725:729 677 glycosylation sites 707:729 677 glycosylation sites 707:729 A total of 399 N-glycoproteins with 677 glycosylation sites were identified in the MFGM fractions of the studied mammals. 27539975 6 46 from components 1076:1085 arg1 yaks 1147:1150 yaks 1147:1150 yaks 1147:1150 N-glycosylated protein components of MFGM fractions from Holstein and Jersey cows, buffaloes, yaks, and goats were more similar to each other compared with those of camels, horses and human. 27539975 6 46 from components 1076:1085 arg1 goats 1157:1161 goats 1157:1161 goats 1157:1161 N-glycosylated protein components of MFGM fractions from Holstein and Jersey cows, buffaloes, yaks, and goats were more similar to each other compared with those of camels, horses and human. 27539975 6 46 from components 1076:1085 arg1 buffaloes 1136:1144 buffaloes 1136:1144 buffaloes 1136:1144 N-glycosylated protein components of MFGM fractions from Holstein and Jersey cows, buffaloes, yaks, and goats were more similar to each other compared with those of camels, horses and human. 27539975 6 46 from components 1076:1085 arg1 cows 1130:1133 Holstein and Jersey cows 1110:1133 Holstein and Jersey cows 1110:1133 N-glycosylated protein components of MFGM fractions from Holstein and Jersey cows, buffaloes, yaks, and goats were more similar to each other compared with those of camels, horses and human. 27539975 7 47 theme useful 1412:1417 arg1 information 1419:1429 useful information 1412:1429 useful information to further explore the mechanism of MFGM glycoproteins biosynthesis among the studied mammals 1412:1523 The findings increased the number of known N-glycosylation sites in the milk from dairy animal species, revealed the complexity of the MFGM glycoproteome, and provided useful information to further explore the mechanism of MFGM glycoproteins biosynthesis among the studied mammals. 27539975 4 48 dep unknown 895:901 arg1 those 857:861 those 857:861 those 857:861 Most glycosylation sites in humans were classified as known and those in the other studied mammals as unknown, according to Swiss-Prot annotations. 27539975 4 48 dep unknown 895:901 arg1 as 892:893 as 892:893 as 892:893 Most glycosylation sites in humans were classified as known and those in the other studied mammals as unknown, according to Swiss-Prot annotations. 27539975 3 49 with N-glycoproteins 686:700 arg1 sites 725:729 677 glycosylation sites 707:729 677 glycosylation sites 707:729 A total of 399 N-glycoproteins with 677 glycosylation sites were identified in the MFGM fractions of the studied mammals. 27539975 7 50 theme glycoproteome 1384:1396 arg1 complexity 1361:1370 the complexity 1357:1370 the complexity of the MFGM glycoproteome 1357:1396 The findings increased the number of known N-glycosylation sites in the milk from dairy animal species, revealed the complexity of the MFGM glycoproteome, and provided useful information to further explore the mechanism of MFGM glycoproteins biosynthesis among the studied mammals. 27539975 5 51 dep stimulus 1030:1037 arg1 GO 1040:1041 GO 1040:1041 ' GO category 1038:1050 Functionally, most of the identified glycoproteins were associated with the 'response to stimulus' GO category. 27539975 1 52 theme much 219:222 arg1 attention 224:232 much attention 219:232 much attention 219:232 Glycosylation of proteins has been implicated in various biological functions and has received much attention; however, glycoprotein components and inter-species complexity have not yet been elucidated fully in milk proteins. 27539975 4 53 theme Swiss-Prot 917:926 arg1 annotations 928:938 Swiss-Prot annotations 917:938 Swiss-Prot annotations 917:938 Most glycosylation sites in humans were classified as known and those in the other studied mammals as unknown, according to Swiss-Prot annotations. 27539975 3 54 theme mammals 784:790 arg1 fractions 759:767 the MFGM fractions 750:767 the MFGM fractions of the studied mammals 750:790 A total of 399 N-glycoproteins with 677 glycosylation sites were identified in the MFGM fractions of the studied mammals. 27539975 2 55 from profiles 581:588 arg1 Jersey 606:611 Jersey 606:611 Jersey 606:611 N-linked glycosylation sites and glycoproteins in milk fat globule membrane (MFGM) fractions were investigated by combining N-glycosylated peptides enrichment and high-accuracy Q Exactive identification, to map the N-glycoproteome profiles in Holstein and Jersey cows, buffaloes, yaks, goats, camels, horses, and humans. 27539975 2 55 from profiles 581:588 arg1 Holstein 593:600 Holstein 593:600 Holstein 593:600 N-linked glycosylation sites and glycoproteins in milk fat globule membrane (MFGM) fractions were investigated by combining N-glycosylated peptides enrichment and high-accuracy Q Exactive identification, to map the N-glycoproteome profiles in Holstein and Jersey cows, buffaloes, yaks, goats, camels, horses, and humans. 27539975 0 56 theme globule 84:90 arg1 proteins 101:108 milk fat globule membrane proteins 75:108 milk fat globule membrane proteins from mammals 75:121 N-glycosylation proteomic characterization and cross-species comparison of milk fat globule membrane proteins from mammals. 27539975 7 57 gly glycoproteins 1472:1484 arg1 glycoproteins 1472:1484 MFGM glycoproteins biosynthesis 1467:1497 MFGM glycoproteins biosynthesis 1467:1497 The findings increased the number of known N-glycosylation sites in the milk from dairy animal species, revealed the complexity of the MFGM glycoproteome, and provided useful information to further explore the mechanism of MFGM glycoproteins biosynthesis among the studied mammals. 27539975 7 58 theme dairy 1326:1330 arg1 species 1339:1345 dairy animal species 1326:1345 dairy animal species 1326:1345 The findings increased the number of known N-glycosylation sites in the milk from dairy animal species, revealed the complexity of the MFGM glycoproteome, and provided useful information to further explore the mechanism of MFGM glycoproteins biosynthesis among the studied mammals. 27539975 0 59 theme proteins 101:108 arg1 characterization 26:41 N-glycosylation proteomic characterization 0:41 N-glycosylation proteomic characterization 0:41 N-glycosylation proteomic characterization and cross-species comparison of milk fat globule membrane proteins from mammals. 27539975 0 59 theme proteins 101:108 arg1 comparison 61:70 cross-species comparison 47:70 cross-species comparison 47:70 N-glycosylation proteomic characterization and cross-species comparison of milk fat globule membrane proteins from mammals. 27539975 7 60 gly N-glycosylation 1287:1301 arg2 species 1339:1345 dairy animal species 1326:1345 dairy animal species 1326:1345 The findings increased the number of known N-glycosylation sites in the milk from dairy animal species, revealed the complexity of the MFGM glycoproteome, and provided useful information to further explore the mechanism of MFGM glycoproteins biosynthesis among the studied mammals. 27539975 7 60 gly N-glycosylation 1287:1301 arg2 sites 1303:1307 known N-glycosylation sites 1281:1307 known N-glycosylation sites in the milk from dairy animal species 1281:1345 The findings increased the number of known N-glycosylation sites in the milk from dairy animal species, revealed the complexity of the MFGM glycoproteome, and provided useful information to further explore the mechanism of MFGM glycoproteins biosynthesis among the studied mammals. 27539975 1 61 theme various 173:179 arg1 functions 192:200 various biological functions 173:200 various biological functions 173:200 Glycosylation of proteins has been implicated in various biological functions and has received much attention; however, glycoprotein components and inter-species complexity have not yet been elucidated fully in milk proteins. 27539975 2 62 theme Exactive 529:536 arg1 peptides 489:496 N-glycosylated peptides 474:496 N-glycosylated peptides enrichment and high-accuracy Q Exactive identification 474:551 N-linked glycosylation sites and glycoproteins in milk fat globule membrane (MFGM) fractions were investigated by combining N-glycosylated peptides enrichment and high-accuracy Q Exactive identification, to map the N-glycoproteome profiles in Holstein and Jersey cows, buffaloes, yaks, goats, camels, horses, and humans. 27539975 2 62 theme Exactive 529:536 arg1 identification 538:551 high-accuracy Q Exactive identification 513:551 high-accuracy Q Exactive identification 513:551 N-linked glycosylation sites and glycoproteins in milk fat globule membrane (MFGM) fractions were investigated by combining N-glycosylated peptides enrichment and high-accuracy Q Exactive identification, to map the N-glycoproteome profiles in Holstein and Jersey cows, buffaloes, yaks, goats, camels, horses, and humans. 27539975 5 63 theme identified 967:976 arg1 glycoproteins 978:990 the identified glycoproteins 963:990 the identified glycoproteins 963:990 Functionally, most of the identified glycoproteins were associated with the 'response to stimulus' GO category. 27539975 2 64 theme N-glycoproteome 565:579 arg1 profiles 581:588 the N-glycoproteome profiles 561:588 the N-glycoproteome profiles in Holstein and Jersey cows, buffaloes, yaks, goats, camels, horses, and humans 561:668 N-linked glycosylation sites and glycoproteins in milk fat globule membrane (MFGM) fractions were investigated by combining N-glycosylated peptides enrichment and high-accuracy Q Exactive identification, to map the N-glycoproteome profiles in Holstein and Jersey cows, buffaloes, yaks, goats, camels, horses, and humans. 27539975 1 65 gly Glycosylation 124:136 arg1 functions 192:200 various biological functions 173:200 various biological functions 173:200 Glycosylation of proteins has been implicated in various biological functions and has received much attention; however, glycoprotein components and inter-species complexity have not yet been elucidated fully in milk proteins. 27539975 1 65 gly Glycosylation 124:136 arg1 proteins 141:148 proteins 141:148 proteins 141:148 Glycosylation of proteins has been implicated in various biological functions and has received much attention; however, glycoprotein components and inter-species complexity have not yet been elucidated fully in milk proteins. 27539975 6 66 theme fractions 1095:1103 arg1 components 1076:1085 N-glycosylated protein components 1053:1085 N-glycosylated protein components of MFGM fractions from Holstein and Jersey cows, buffaloes, yaks, and goats 1053:1161 N-glycosylated protein components of MFGM fractions from Holstein and Jersey cows, buffaloes, yaks, and goats were more similar to each other compared with those of camels, horses and human. 27539975 0 67 from comparison 61:70 arg1 mammals 115:121 mammals 115:121 mammals 115:121 N-glycosylation proteomic characterization and cross-species comparison of milk fat globule membrane proteins from mammals. 27539975 0 68 theme proteomic 16:24 arg1 characterization 26:41 N-glycosylation proteomic characterization 0:41 N-glycosylation proteomic characterization 0:41 N-glycosylation proteomic characterization and cross-species comparison of milk fat globule membrane proteins from mammals. 27539975 2 69 dep peptides 489:496 arg1 peptides 489:496 N-glycosylated peptides 474:496 N-glycosylated peptides enrichment and high-accuracy Q Exactive identification 474:551 N-linked glycosylation sites and glycoproteins in milk fat globule membrane (MFGM) fractions were investigated by combining N-glycosylated peptides enrichment and high-accuracy Q Exactive identification, to map the N-glycoproteome profiles in Holstein and Jersey cows, buffaloes, yaks, goats, camels, horses, and humans. 27539975 2 69 dep peptides 489:496 arg1 identification 538:551 high-accuracy Q Exactive identification 513:551 high-accuracy Q Exactive identification 513:551 N-linked glycosylation sites and glycoproteins in milk fat globule membrane (MFGM) fractions were investigated by combining N-glycosylated peptides enrichment and high-accuracy Q Exactive identification, to map the N-glycoproteome profiles in Holstein and Jersey cows, buffaloes, yaks, goats, camels, horses, and humans. 27539975 2 69 dep peptides 489:496 arg1 enrichment 498:507 enrichment 498:507 enrichment 498:507 N-linked glycosylation sites and glycoproteins in milk fat globule membrane (MFGM) fractions were investigated by combining N-glycosylated peptides enrichment and high-accuracy Q Exactive identification, to map the N-glycoproteome profiles in Holstein and Jersey cows, buffaloes, yaks, goats, camels, horses, and humans. 27539975 7 70 from species 1339:1345 arg1 sites 1303:1307 known N-glycosylation sites 1281:1307 known N-glycosylation sites in the milk from dairy animal species 1281:1345 The findings increased the number of known N-glycosylation sites in the milk from dairy animal species, revealed the complexity of the MFGM glycoproteome, and provided useful information to further explore the mechanism of MFGM glycoproteins biosynthesis among the studied mammals. 27539975 7 70 from species 1339:1345 arg1 milk 1316:1319 the milk 1312:1319 the milk from dairy animal species 1312:1345 The findings increased the number of known N-glycosylation sites in the milk from dairy animal species, revealed the complexity of the MFGM glycoproteome, and provided useful information to further explore the mechanism of MFGM glycoproteins biosynthesis among the studied mammals. 27539975 7 71 theme sites 1303:1307 arg1 number 1271:1276 the number 1267:1276 the number of known N-glycosylation sites in the milk from dairy animal species 1267:1345 The findings increased the number of known N-glycosylation sites in the milk from dairy animal species, revealed the complexity of the MFGM glycoproteome, and provided useful information to further explore the mechanism of MFGM glycoproteins biosynthesis among the studied mammals. 27539975 2 72 theme N-glycosylated 474:487 arg1 peptides 489:496 N-glycosylated peptides 474:496 N-glycosylated peptides enrichment and high-accuracy Q Exactive identification 474:551 N-linked glycosylation sites and glycoproteins in milk fat globule membrane (MFGM) fractions were investigated by combining N-glycosylated peptides enrichment and high-accuracy Q Exactive identification, to map the N-glycoproteome profiles in Holstein and Jersey cows, buffaloes, yaks, goats, camels, horses, and humans. 27539975 2 72 theme N-glycosylated 474:487 arg1 identification 538:551 high-accuracy Q Exactive identification 513:551 high-accuracy Q Exactive identification 513:551 N-linked glycosylation sites and glycoproteins in milk fat globule membrane (MFGM) fractions were investigated by combining N-glycosylated peptides enrichment and high-accuracy Q Exactive identification, to map the N-glycoproteome profiles in Holstein and Jersey cows, buffaloes, yaks, goats, camels, horses, and humans. 27539975 2 72 theme N-glycosylated 474:487 arg1 enrichment 498:507 enrichment 498:507 enrichment 498:507 N-linked glycosylation sites and glycoproteins in milk fat globule membrane (MFGM) fractions were investigated by combining N-glycosylated peptides enrichment and high-accuracy Q Exactive identification, to map the N-glycoproteome profiles in Holstein and Jersey cows, buffaloes, yaks, goats, camels, horses, and humans. 27539975 2 73 theme globule 409:415 arg1 fractions 433:441 milk fat globule membrane (MFGM) fractions 400:441 milk fat globule membrane (MFGM) fractions 400:441 N-linked glycosylation sites and glycoproteins in milk fat globule membrane (MFGM) fractions were investigated by combining N-glycosylated peptides enrichment and high-accuracy Q Exactive identification, to map the N-glycoproteome profiles in Holstein and Jersey cows, buffaloes, yaks, goats, camels, horses, and humans. 27539975 7 74 theme known 1281:1285 arg1 sites 1303:1307 known N-glycosylation sites 1281:1307 known N-glycosylation sites in the milk from dairy animal species 1281:1345 The findings increased the number of known N-glycosylation sites in the milk from dairy animal species, revealed the complexity of the MFGM glycoproteome, and provided useful information to further explore the mechanism of MFGM glycoproteins biosynthesis among the studied mammals. 27539975 6 75 from goats 1157:1161 arg1 components 1076:1085 N-glycosylated protein components 1053:1085 N-glycosylated protein components of MFGM fractions from Holstein and Jersey cows, buffaloes, yaks, and goats 1053:1161 N-glycosylated protein components of MFGM fractions from Holstein and Jersey cows, buffaloes, yaks, and goats were more similar to each other compared with those of camels, horses and human. 27539975 6 75 from goats 1157:1161 arg1 fractions 1095:1103 MFGM fractions 1090:1103 MFGM fractions from Holstein and Jersey cows, buffaloes, yaks, and goats 1090:1161 N-glycosylated protein components of MFGM fractions from Holstein and Jersey cows, buffaloes, yaks, and goats were more similar to each other compared with those of camels, horses and human. 27539975 4 76 gly glycosylation 798:810 arg2 sites 812:816 Most glycosylation sites 793:816 Most glycosylation sites in humans 793:826 Most glycosylation sites in humans were classified as known and those in the other studied mammals as unknown, according to Swiss-Prot annotations. 27539975 2 77 theme high-accuracy 513:525 arg1 peptides 489:496 N-glycosylated peptides 474:496 N-glycosylated peptides enrichment and high-accuracy Q Exactive identification 474:551 N-linked glycosylation sites and glycoproteins in milk fat globule membrane (MFGM) fractions were investigated by combining N-glycosylated peptides enrichment and high-accuracy Q Exactive identification, to map the N-glycoproteome profiles in Holstein and Jersey cows, buffaloes, yaks, goats, camels, horses, and humans. 27539975 2 77 theme high-accuracy 513:525 arg1 identification 538:551 high-accuracy Q Exactive identification 513:551 high-accuracy Q Exactive identification 513:551 N-linked glycosylation sites and glycoproteins in milk fat globule membrane (MFGM) fractions were investigated by combining N-glycosylated peptides enrichment and high-accuracy Q Exactive identification, to map the N-glycoproteome profiles in Holstein and Jersey cows, buffaloes, yaks, goats, camels, horses, and humans. 27539975 0 78 theme milk 75:78 arg1 proteins 101:108 milk fat globule membrane proteins 75:108 milk fat globule membrane proteins from mammals 75:121 N-glycosylation proteomic characterization and cross-species comparison of milk fat globule membrane proteins from mammals. 27539975 1 79 theme milk 335:338 arg1 proteins 340:347 milk proteins 335:347 milk proteins 335:347 Glycosylation of proteins has been implicated in various biological functions and has received much attention; however, glycoprotein components and inter-species complexity have not yet been elucidated fully in milk proteins. 27539975 2 80 gly N-glycosylated 474:487 arg1 peptides 489:496 N-glycosylated peptides 474:496 N-glycosylated peptides enrichment and high-accuracy Q Exactive identification 474:551 N-linked glycosylation sites and glycoproteins in milk fat globule membrane (MFGM) fractions were investigated by combining N-glycosylated peptides enrichment and high-accuracy Q Exactive identification, to map the N-glycoproteome profiles in Holstein and Jersey cows, buffaloes, yaks, goats, camels, horses, and humans. 27539975 2 80 gly N-glycosylated 474:487 arg1 identification 538:551 high-accuracy Q Exactive identification 513:551 high-accuracy Q Exactive identification 513:551 N-linked glycosylation sites and glycoproteins in milk fat globule membrane (MFGM) fractions were investigated by combining N-glycosylated peptides enrichment and high-accuracy Q Exactive identification, to map the N-glycoproteome profiles in Holstein and Jersey cows, buffaloes, yaks, goats, camels, horses, and humans. 27539975 2 80 gly N-glycosylated 474:487 arg1 enrichment 498:507 enrichment 498:507 enrichment 498:507 N-linked glycosylation sites and glycoproteins in milk fat globule membrane (MFGM) fractions were investigated by combining N-glycosylated peptides enrichment and high-accuracy Q Exactive identification, to map the N-glycoproteome profiles in Holstein and Jersey cows, buffaloes, yaks, goats, camels, horses, and humans. 27539975 3 81 gly N-glycoproteins 686:700 arg1 N-glycoproteins 686:700 399 N-glycoproteins 682:700 399 N-glycoproteins with 677 glycosylation sites 682:729 A total of 399 N-glycoproteins with 677 glycosylation sites were identified in the MFGM fractions of the studied mammals. 27539975 2 82 gly glycosylation 359:371 arg2 sites 373:377 N-linked glycosylation sites 350:377 N-linked glycosylation sites 350:377 N-linked glycosylation sites and glycoproteins in milk fat globule membrane (MFGM) fractions were investigated by combining N-glycosylated peptides enrichment and high-accuracy Q Exactive identification, to map the N-glycoproteome profiles in Holstein and Jersey cows, buffaloes, yaks, goats, camels, horses, and humans. 27539975 4 83 theme glycosylation 798:810 arg1 sites 812:816 Most glycosylation sites 793:816 Most glycosylation sites in humans 793:826 Most glycosylation sites in humans were classified as known and those in the other studied mammals as unknown, according to Swiss-Prot annotations. 27539975 2 84 theme N-linked 350:357 arg1 sites 373:377 N-linked glycosylation sites 350:377 N-linked glycosylation sites 350:377 N-linked glycosylation sites and glycoproteins in milk fat globule membrane (MFGM) fractions were investigated by combining N-glycosylated peptides enrichment and high-accuracy Q Exactive identification, to map the N-glycoproteome profiles in Holstein and Jersey cows, buffaloes, yaks, goats, camels, horses, and humans. 27539975 1 85 theme glycoprotein 244:255 arg1 components 257:266 glycoprotein components 244:266 glycoprotein components 244:266 Glycosylation of proteins has been implicated in various biological functions and has received much attention; however, glycoprotein components and inter-species complexity have not yet been elucidated fully in milk proteins. 27539975 7 86 theme biosynthesis 1486:1497 arg1 mechanism 1454:1462 the mechanism 1450:1462 the mechanism of MFGM glycoproteins biosynthesis among the studied mammals 1450:1523 The findings increased the number of known N-glycosylation sites in the milk from dairy animal species, revealed the complexity of the MFGM glycoproteome, and provided useful information to further explore the mechanism of MFGM glycoproteins biosynthesis among the studied mammals. 27539975 6 87 theme Jersey 1123:1128 arg1 cows 1130:1133 Holstein and Jersey cows 1110:1133 Holstein and Jersey cows 1110:1133 N-glycosylated protein components of MFGM fractions from Holstein and Jersey cows, buffaloes, yaks, and goats were more similar to each other compared with those of camels, horses and human. 27539975 3 88 theme glycosylation 711:723 arg1 sites 725:729 677 glycosylation sites 707:729 677 glycosylation sites 707:729 A total of 399 N-glycoproteins with 677 glycosylation sites were identified in the MFGM fractions of the studied mammals. 27539975 2 89 theme milk 400:403 arg1 fat 405:407 milk fat 400:407 milk fat globule membrane (MFGM) fractions 400:441 N-linked glycosylation sites and glycoproteins in milk fat globule membrane (MFGM) fractions were investigated by combining N-glycosylated peptides enrichment and high-accuracy Q Exactive identification, to map the N-glycoproteome profiles in Holstein and Jersey cows, buffaloes, yaks, goats, camels, horses, and humans. 24529077 8 0 theme crucial 1168:1174 arg1 step 1176:1179 a crucial step 1166:1179 a crucial step toward systematically revealing the functionality of N-glycosylated RJ proteins 1166:1259 CONCLUSION: Our in-depth, large-scale mapping of novel glycosylation sites represents a crucial step toward systematically revealing the functionality of N-glycosylated RJ proteins, and is potentially useful for producing a protein with desirable pharmacokinetic and biological activity using a genetic engineering approach. 24529077 4 1 theme better 608:613 arg1 understanding 615:627 a better understanding 606:627 a better understanding of novel and glycosylated proteins in RJ 606:668 We used two different liquid chromatography-tandem mass spectrometry techniques, complementary N-glycopeptide enrichment strategies, and bioinformatic approaches to gain a better understanding of novel and glycosylated proteins in RJ. 24529077 6 2 theme glycosylated 876:887 arg1 proteins 889:896 the glycosylated proteins 872:896 the glycosylated proteins 872:896 Most of the glycosylated proteins were related to metabolic activities and health improvement. 24529077 10 3 theme glycoproteome 1620:1632 arg1 levels 1634:1639 both the proteome and glycoproteome levels 1598:1639 levels 1634:1639 These findings contribute vital and new knowledge to our understanding of the innate biochemical nature of RJ at both the proteome and glycoproteome levels. 24529077 5 4 theme glycosylation 807:819 arg1 novel 842:846 novel 842:846 novel 842:846 RESULTS: A total of 25 N-glycosylated proteins, carrying 53 N-glycosylation sites, were identified in RJ proteins, of which 42 N-linked glycosylation sites were mapped as novel on RJ proteins. 24529077 5 4 theme glycosylation 807:819 arg1 sites 821:825 42 N-linked glycosylation sites 795:825 42 N-linked glycosylation sites 795:825 RESULTS: A total of 25 N-glycosylated proteins, carrying 53 N-glycosylation sites, were identified in RJ proteins, of which 42 N-linked glycosylation sites were mapped as novel on RJ proteins. 24529077 2 5 theme human 284:288 arg1 health 290:295 human health 284:295 human health 284:295 It plays vital roles in honeybee biology and in the improvement of human health. 24529077 4 6 from RJ 667:668 arg1 understanding 615:627 a better understanding 606:627 a better understanding of novel and glycosylated proteins in RJ 606:668 We used two different liquid chromatography-tandem mass spectrometry techniques, complementary N-glycopeptide enrichment strategies, and bioinformatic approaches to gain a better understanding of novel and glycosylated proteins in RJ. 24529077 8 7 theme N-glycosylated 1234:1247 arg1 proteins 1252:1259 N-glycosylated RJ proteins 1234:1259 N-glycosylated RJ proteins 1234:1259 CONCLUSION: Our in-depth, large-scale mapping of novel glycosylation sites represents a crucial step toward systematically revealing the functionality of N-glycosylated RJ proteins, and is potentially useful for producing a protein with desirable pharmacokinetic and biological activity using a genetic engineering approach. 24529077 4 8 theme proteins 655:662 arg1 understanding 615:627 a better understanding 606:627 a better understanding of novel and glycosylated proteins in RJ 606:668 We used two different liquid chromatography-tandem mass spectrometry techniques, complementary N-glycopeptide enrichment strategies, and bioinformatic approaches to gain a better understanding of novel and glycosylated proteins in RJ. 24529077 4 9 from proteins 655:662 arg1 RJ 667:668 RJ 667:668 RJ 667:668 We used two different liquid chromatography-tandem mass spectrometry techniques, complementary N-glycopeptide enrichment strategies, and bioinformatic approaches to gain a better understanding of novel and glycosylated proteins in RJ. 24529077 8 10 theme proteins 1252:1259 arg1 functionality 1217:1229 the functionality 1213:1229 the functionality of N-glycosylated RJ proteins 1213:1259 CONCLUSION: Our in-depth, large-scale mapping of novel glycosylation sites represents a crucial step toward systematically revealing the functionality of N-glycosylated RJ proteins, and is potentially useful for producing a protein with desirable pharmacokinetic and biological activity using a genetic engineering approach. 24529077 1 11 theme nurse 205:209 arg1 bees 211:214 nurse bees 205:214 nurse bees 205:214 BACKGROUND: Royal jelly (RJ) is a proteinaceous secretion produced from the hypopharyngeal and mandibular glands of nurse bees. 24529077 6 12 theme health 939:944 arg1 improvement 946:956 health improvement 939:956 health improvement 939:956 Most of the glycosylated proteins were related to metabolic activities and health improvement. 24529077 8 13 theme pharmacokinetic 1327:1341 arg1 activity 1358:1365 desirable pharmacokinetic and biological activity 1317:1365 desirable pharmacokinetic and biological activity using a genetic engineering approach 1317:1402 CONCLUSION: Our in-depth, large-scale mapping of novel glycosylation sites represents a crucial step toward systematically revealing the functionality of N-glycosylated RJ proteins, and is potentially useful for producing a protein with desirable pharmacokinetic and biological activity using a genetic engineering approach. 24529077 7 14 theme improvement 1056:1066 arg1 activities 1068:1077 health improvement activities 1049:1077 health improvement activities 1049:1077 The 13 newly identified proteins were also mainly associated with metabolic processes and health improvement activities. 24529077 8 15 theme biological 1347:1356 arg1 activity 1358:1365 desirable pharmacokinetic and biological activity 1317:1365 desirable pharmacokinetic and biological activity using a genetic engineering approach 1317:1402 CONCLUSION: Our in-depth, large-scale mapping of novel glycosylation sites represents a crucial step toward systematically revealing the functionality of N-glycosylated RJ proteins, and is potentially useful for producing a protein with desirable pharmacokinetic and biological activity using a genetic engineering approach. 24529077 5 16 theme N-glycosylated 694:707 arg1 proteins 709:716 25 N-glycosylated proteins 691:716 25 N-glycosylated proteins 691:716 RESULTS: A total of 25 N-glycosylated proteins, carrying 53 N-glycosylation sites, were identified in RJ proteins, of which 42 N-linked glycosylation sites were mapped as novel on RJ proteins. 24529077 4 17 used used 439:442 arg2 We 436:437 We 436:437 We 436:437 We used two different liquid chromatography-tandem mass spectrometry techniques, complementary N-glycopeptide enrichment strategies, and bioinformatic approaches to gain a better understanding of novel and glycosylated proteins in RJ. 24529077 2 18 theme vital 226:230 arg1 roles 232:236 vital roles 226:236 vital roles 226:236 It plays vital roles in honeybee biology and in the improvement of human health. 24529077 7 19 theme identified 972:981 arg1 proteins 983:990 The 13 newly identified proteins 959:990 The 13 newly identified proteins 959:990 The 13 newly identified proteins were also mainly associated with metabolic processes and health improvement activities. 24529077 1 20 theme proteinaceous 123:135 arg1 secretion 137:145 a proteinaceous secretion 121:145 a proteinaceous secretion produced from the hypopharyngeal and mandibular glands of nurse bees 121:214 BACKGROUND: Royal jelly (RJ) is a proteinaceous secretion produced from the hypopharyngeal and mandibular glands of nurse bees. 24529077 1 20 theme proteinaceous 123:135 arg1 BACKGROUND 89:98 BACKGROUND 89:98 BACKGROUND: Royal jelly (RJ) is a proteinaceous secretion produced from the hypopharyngeal and mandibular glands of nurse bees. 89:215 BACKGROUND: Royal jelly (RJ) is a proteinaceous secretion produced from the hypopharyngeal and mandibular glands of nurse bees. 24529077 1 20 theme proteinaceous 123:135 arg1 jelly 107:111 Royal jelly 101:111 Royal jelly (RJ) 101:116 BACKGROUND: Royal jelly (RJ) is a proteinaceous secretion produced from the hypopharyngeal and mandibular glands of nurse bees. 24529077 4 21 theme mass 487:490 arg1 spectrometry 492:503 liquid chromatography-tandem mass spectrometry 458:503 two different liquid chromatography-tandem mass spectrometry techniques 444:514 We used two different liquid chromatography-tandem mass spectrometry techniques, complementary N-glycopeptide enrichment strategies, and bioinformatic approaches to gain a better understanding of novel and glycosylated proteins in RJ. 24529077 10 22 theme new 1521:1523 arg1 knowledge 1525:1533 vital and new knowledge 1511:1533 vital and new knowledge 1511:1533 These findings contribute vital and new knowledge to our understanding of the innate biochemical nature of RJ at both the proteome and glycoproteome levels. 24529077 8 23 theme genetic 1375:1381 arg1 approach 1395:1402 a genetic engineering approach 1373:1402 a genetic engineering approach 1373:1402 CONCLUSION: Our in-depth, large-scale mapping of novel glycosylation sites represents a crucial step toward systematically revealing the functionality of N-glycosylated RJ proteins, and is potentially useful for producing a protein with desirable pharmacokinetic and biological activity using a genetic engineering approach. 24529077 4 24 from understanding 615:627 arg1 RJ 667:668 RJ 667:668 RJ 667:668 We used two different liquid chromatography-tandem mass spectrometry techniques, complementary N-glycopeptide enrichment strategies, and bioinformatic approaches to gain a better understanding of novel and glycosylated proteins in RJ. 24529077 3 25 from sites 384:388 arg1 proteins 396:403 RJ proteins 393:403 RJ proteins 393:403 However, some proteins remain unknown in RJ, and mapping N-glycosylation modification sites on RJ proteins demands further investigation. 24529077 10 26 from nature 1582:1587 arg1 levels 1634:1639 both the proteome and glycoproteome levels 1598:1639 levels 1634:1639 These findings contribute vital and new knowledge to our understanding of the innate biochemical nature of RJ at both the proteome and glycoproteome levels. 24529077 10 27 theme vital 1511:1515 arg1 knowledge 1525:1533 vital and new knowledge 1511:1533 vital and new knowledge 1511:1533 These findings contribute vital and new knowledge to our understanding of the innate biochemical nature of RJ at both the proteome and glycoproteome levels. 24529077 3 28 gly N-glycosylation 355:369 arg2 sites 384:388 mapping N-glycosylation modification sites 347:388 mapping N-glycosylation modification sites on RJ proteins 347:403 However, some proteins remain unknown in RJ, and mapping N-glycosylation modification sites on RJ proteins demands further investigation. 24529077 4 29 theme liquid 458:463 arg1 spectrometry 492:503 liquid chromatography-tandem mass spectrometry 458:503 two different liquid chromatography-tandem mass spectrometry techniques 444:514 We used two different liquid chromatography-tandem mass spectrometry techniques, complementary N-glycopeptide enrichment strategies, and bioinformatic approaches to gain a better understanding of novel and glycosylated proteins in RJ. 24529077 3 30 theme RJ 393:394 arg1 proteins 396:403 RJ proteins 393:403 RJ proteins 393:403 However, some proteins remain unknown in RJ, and mapping N-glycosylation modification sites on RJ proteins demands further investigation. 24529077 0 31 theme Comprehensive 0:12 arg1 identification 14:27 Comprehensive identification 0:27 Comprehensive identification of novel proteins and N-glycosylation sites in royal jelly. 0:87 Comprehensive identification of novel proteins and N-glycosylation sites in royal jelly. 24529077 5 32 contain carrying 719:726 arg2 sites 747:751 53 N-glycosylation sites 728:751 53 N-glycosylation sites 728:751 RESULTS: A total of 25 N-glycosylated proteins, carrying 53 N-glycosylation sites, were identified in RJ proteins, of which 42 N-linked glycosylation sites were mapped as novel on RJ proteins. 24529077 5 32 contain carrying 719:726 arg1 proteins 709:716 25 N-glycosylated proteins 691:716 25 N-glycosylated proteins 691:716 RESULTS: A total of 25 N-glycosylated proteins, carrying 53 N-glycosylation sites, were identified in RJ proteins, of which 42 N-linked glycosylation sites were mapped as novel on RJ proteins. 24529077 10 33 theme biochemical 1570:1580 arg1 nature 1582:1587 the innate biochemical nature 1559:1587 the innate biochemical nature of RJ at both the proteome and glycoproteome levels 1559:1639 These findings contribute vital and new knowledge to our understanding of the innate biochemical nature of RJ at both the proteome and glycoproteome levels. 24529077 4 34 theme bioinformatic 573:585 arg1 approaches 587:596 bioinformatic approaches 573:596 bioinformatic approaches 573:596 We used two different liquid chromatography-tandem mass spectrometry techniques, complementary N-glycopeptide enrichment strategies, and bioinformatic approaches to gain a better understanding of novel and glycosylated proteins in RJ. 24529077 5 35 gly glycosylation 807:819 arg2 sites 821:825 42 N-linked glycosylation sites 795:825 42 N-linked glycosylation sites 795:825 RESULTS: A total of 25 N-glycosylated proteins, carrying 53 N-glycosylation sites, were identified in RJ proteins, of which 42 N-linked glycosylation sites were mapped as novel on RJ proteins. 24529077 5 35 gly glycosylation 807:819 arg2 42 795:796 42 795:796 42 795:796 RESULTS: A total of 25 N-glycosylated proteins, carrying 53 N-glycosylation sites, were identified in RJ proteins, of which 42 N-linked glycosylation sites were mapped as novel on RJ proteins. 24529077 5 35 gly glycosylation 807:819 arg2 novel 842:846 novel 842:846 novel 842:846 RESULTS: A total of 25 N-glycosylated proteins, carrying 53 N-glycosylation sites, were identified in RJ proteins, of which 42 N-linked glycosylation sites were mapped as novel on RJ proteins. 24529077 8 36 gly glycosylation 1135:1147 arg2 sites 1149:1153 novel glycosylation sites 1129:1153 novel glycosylation sites 1129:1153 CONCLUSION: Our in-depth, large-scale mapping of novel glycosylation sites represents a crucial step toward systematically revealing the functionality of N-glycosylated RJ proteins, and is potentially useful for producing a protein with desirable pharmacokinetic and biological activity using a genetic engineering approach. 24529077 0 37 theme proteins 38:45 arg1 identification 14:27 Comprehensive identification 0:27 Comprehensive identification of novel proteins and N-glycosylation sites in royal jelly. 0:87 Comprehensive identification of novel proteins and N-glycosylation sites in royal jelly. 24529077 9 38 theme newly-identified 1409:1424 arg1 proteins 1426:1433 The newly-identified proteins 1405:1433 The newly-identified proteins 1405:1433 The newly-identified proteins significantly extend the proteome coverage of RJ. 24529077 3 39 theme N-glycosylation 355:369 arg1 sites 384:388 mapping N-glycosylation modification sites 347:388 mapping N-glycosylation modification sites on RJ proteins 347:403 However, some proteins remain unknown in RJ, and mapping N-glycosylation modification sites on RJ proteins demands further investigation. 24529077 4 40 theme complementary 517:529 arg1 strategies 557:566 complementary N-glycopeptide enrichment strategies 517:566 complementary N-glycopeptide enrichment strategies 517:566 We used two different liquid chromatography-tandem mass spectrometry techniques, complementary N-glycopeptide enrichment strategies, and bioinformatic approaches to gain a better understanding of novel and glycosylated proteins in RJ. 24529077 0 41 theme N-glycosylation 51:65 arg1 sites 67:71 N-glycosylation sites 51:71 N-glycosylation sites 51:71 Comprehensive identification of novel proteins and N-glycosylation sites in royal jelly. 24529077 10 42 from levels 1634:1639 arg1 RJ 1592:1593 RJ 1592:1593 RJ at both the proteome and glycoproteome levels 1592:1639 These findings contribute vital and new knowledge to our understanding of the innate biochemical nature of RJ at both the proteome and glycoproteome levels. 24529077 10 42 from levels 1634:1639 arg1 nature 1582:1587 the innate biochemical nature 1559:1587 the innate biochemical nature of RJ at both the proteome and glycoproteome levels 1559:1639 These findings contribute vital and new knowledge to our understanding of the innate biochemical nature of RJ at both the proteome and glycoproteome levels. 24529077 4 43 theme enrichment 546:555 arg1 strategies 557:566 complementary N-glycopeptide enrichment strategies 517:566 complementary N-glycopeptide enrichment strategies 517:566 We used two different liquid chromatography-tandem mass spectrometry techniques, complementary N-glycopeptide enrichment strategies, and bioinformatic approaches to gain a better understanding of novel and glycosylated proteins in RJ. 24529077 1 44 theme bees 211:214 arg1 glands 195:200 the hypopharyngeal and mandibular glands 161:200 glands 195:200 BACKGROUND: Royal jelly (RJ) is a proteinaceous secretion produced from the hypopharyngeal and mandibular glands of nurse bees. 24529077 8 45 theme novel 1129:1133 arg1 sites 1149:1153 novel glycosylation sites 1129:1153 novel glycosylation sites 1129:1153 CONCLUSION: Our in-depth, large-scale mapping of novel glycosylation sites represents a crucial step toward systematically revealing the functionality of N-glycosylated RJ proteins, and is potentially useful for producing a protein with desirable pharmacokinetic and biological activity using a genetic engineering approach. 24529077 8 46 theme sites 1149:1153 arg1 mapping 1118:1124 Our in-depth, large-scale mapping 1092:1124 Our in-depth, large-scale mapping of novel glycosylation sites 1092:1153 CONCLUSION: Our in-depth, large-scale mapping of novel glycosylation sites represents a crucial step toward systematically revealing the functionality of N-glycosylated RJ proteins, and is potentially useful for producing a protein with desirable pharmacokinetic and biological activity using a genetic engineering approach. 24529077 6 47 theme metabolic 914:922 arg1 activities 924:933 metabolic activities 914:933 metabolic activities 914:933 Most of the glycosylated proteins were related to metabolic activities and health improvement. 24529077 4 48 theme novel 632:636 arg1 proteins 655:662 novel and glycosylated proteins 632:662 novel and glycosylated proteins in RJ 632:668 We used two different liquid chromatography-tandem mass spectrometry techniques, complementary N-glycopeptide enrichment strategies, and bioinformatic approaches to gain a better understanding of novel and glycosylated proteins in RJ. 24529077 9 49 theme RJ 1481:1482 arg1 coverage 1469:1476 the proteome coverage 1456:1476 the proteome coverage of RJ 1456:1482 The newly-identified proteins significantly extend the proteome coverage of RJ. 24529077 5 50 gly N-glycosylated 694:707 arg1 proteins 709:716 25 N-glycosylated proteins 691:716 25 N-glycosylated proteins 691:716 RESULTS: A total of 25 N-glycosylated proteins, carrying 53 N-glycosylation sites, were identified in RJ proteins, of which 42 N-linked glycosylation sites were mapped as novel on RJ proteins. 24529077 8 51 with protein 1304:1310 arg1 activity 1358:1365 desirable pharmacokinetic and biological activity 1317:1365 desirable pharmacokinetic and biological activity using a genetic engineering approach 1317:1402 CONCLUSION: Our in-depth, large-scale mapping of novel glycosylation sites represents a crucial step toward systematically revealing the functionality of N-glycosylated RJ proteins, and is potentially useful for producing a protein with desirable pharmacokinetic and biological activity using a genetic engineering approach. 24529077 4 52 gly glycosylated 642:653 arg1 proteins 655:662 novel and glycosylated proteins 632:662 novel and glycosylated proteins in RJ 632:668 We used two different liquid chromatography-tandem mass spectrometry techniques, complementary N-glycopeptide enrichment strategies, and bioinformatic approaches to gain a better understanding of novel and glycosylated proteins in RJ. 24529077 8 53 gly N-glycosylated 1234:1247 arg1 proteins 1252:1259 N-glycosylated RJ proteins 1234:1259 N-glycosylated RJ proteins 1234:1259 CONCLUSION: Our in-depth, large-scale mapping of novel glycosylation sites represents a crucial step toward systematically revealing the functionality of N-glycosylated RJ proteins, and is potentially useful for producing a protein with desirable pharmacokinetic and biological activity using a genetic engineering approach. 24529077 5 54 theme RJ 851:852 arg1 proteins 854:861 RJ proteins 851:861 RJ proteins 851:861 RESULTS: A total of 25 N-glycosylated proteins, carrying 53 N-glycosylation sites, were identified in RJ proteins, of which 42 N-linked glycosylation sites were mapped as novel on RJ proteins. 24529077 2 55 theme health 290:295 arg1 improvement 269:279 the improvement 265:279 the improvement of human health 265:295 It plays vital roles in honeybee biology and in the improvement of human health. 24529077 1 56 theme hypopharyngeal 165:178 arg1 glands 195:200 the hypopharyngeal and mandibular glands 161:200 glands 195:200 BACKGROUND: Royal jelly (RJ) is a proteinaceous secretion produced from the hypopharyngeal and mandibular glands of nurse bees. 24529077 5 57 theme proteins 709:716 arg1 total 682:686 A total 680:686 A total of 25 N-glycosylated proteins, carrying 53 N-glycosylation sites, 680:752 RESULTS: A total of 25 N-glycosylated proteins, carrying 53 N-glycosylation sites, were identified in RJ proteins, of which 42 N-linked glycosylation sites were mapped as novel on RJ proteins. 24529077 1 58 theme mandibular 184:193 arg1 glands 195:200 the hypopharyngeal and mandibular glands 161:200 glands 195:200 BACKGROUND: Royal jelly (RJ) is a proteinaceous secretion produced from the hypopharyngeal and mandibular glands of nurse bees. 24529077 4 59 theme glycosylated 642:653 arg1 proteins 655:662 novel and glycosylated proteins 632:662 novel and glycosylated proteins in RJ 632:668 We used two different liquid chromatography-tandem mass spectrometry techniques, complementary N-glycopeptide enrichment strategies, and bioinformatic approaches to gain a better understanding of novel and glycosylated proteins in RJ. 24529077 8 60 theme RJ 1249:1250 arg1 proteins 1252:1259 N-glycosylated RJ proteins 1234:1259 N-glycosylated RJ proteins 1234:1259 CONCLUSION: Our in-depth, large-scale mapping of novel glycosylation sites represents a crucial step toward systematically revealing the functionality of N-glycosylated RJ proteins, and is potentially useful for producing a protein with desirable pharmacokinetic and biological activity using a genetic engineering approach. 24529077 8 61 dep in-depth 1096:1103 arg1 large-scale 1106:1116 large-scale 1106:1116 large-scale 1106:1116 CONCLUSION: Our in-depth, large-scale mapping of novel glycosylation sites represents a crucial step toward systematically revealing the functionality of N-glycosylated RJ proteins, and is potentially useful for producing a protein with desirable pharmacokinetic and biological activity using a genetic engineering approach. 24529077 7 62 theme health 1049:1054 arg1 activities 1068:1077 health improvement activities 1049:1077 health improvement activities 1049:1077 The 13 newly identified proteins were also mainly associated with metabolic processes and health improvement activities. 24529077 7 63 theme metabolic 1025:1033 arg1 processes 1035:1043 metabolic processes 1025:1043 metabolic processes 1025:1043 The 13 newly identified proteins were also mainly associated with metabolic processes and health improvement activities. 24529077 8 64 theme desirable 1317:1325 arg1 activity 1358:1365 desirable pharmacokinetic and biological activity 1317:1365 desirable pharmacokinetic and biological activity using a genetic engineering approach 1317:1402 CONCLUSION: Our in-depth, large-scale mapping of novel glycosylation sites represents a crucial step toward systematically revealing the functionality of N-glycosylated RJ proteins, and is potentially useful for producing a protein with desirable pharmacokinetic and biological activity using a genetic engineering approach. 24529077 6 65 gly glycosylated 876:887 arg1 proteins 889:896 the glycosylated proteins 872:896 the glycosylated proteins 872:896 Most of the glycosylated proteins were related to metabolic activities and health improvement. 24529077 2 66 theme honeybee 241:248 arg1 biology 250:256 honeybee biology 241:256 honeybee biology 241:256 It plays vital roles in honeybee biology and in the improvement of human health. 24529077 0 67 theme royal 76:80 arg1 jelly 82:86 royal jelly 76:86 royal jelly 76:86 Comprehensive identification of novel proteins and N-glycosylation sites in royal jelly. 24529077 5 68 link N-linked 798:805 arg1 novel 842:846 novel 842:846 novel 842:846 RESULTS: A total of 25 N-glycosylated proteins, carrying 53 N-glycosylation sites, were identified in RJ proteins, of which 42 N-linked glycosylation sites were mapped as novel on RJ proteins. 24529077 5 68 link N-linked 798:805 arg1 sites 821:825 42 N-linked glycosylation sites 795:825 42 N-linked glycosylation sites 795:825 RESULTS: A total of 25 N-glycosylated proteins, carrying 53 N-glycosylation sites, were identified in RJ proteins, of which 42 N-linked glycosylation sites were mapped as novel on RJ proteins. 24529077 4 69 gly N-glycopeptide 531:544 arg2 N-glycopeptide 531:544 complementary N-glycopeptide enrichment strategies 517:566 complementary N-glycopeptide enrichment strategies 517:566 We used two different liquid chromatography-tandem mass spectrometry techniques, complementary N-glycopeptide enrichment strategies, and bioinformatic approaches to gain a better understanding of novel and glycosylated proteins in RJ. 24529077 4 70 theme spectrometry 492:503 arg1 techniques 505:514 two different liquid chromatography-tandem mass spectrometry techniques 444:514 two different liquid chromatography-tandem mass spectrometry techniques 444:514 We used two different liquid chromatography-tandem mass spectrometry techniques, complementary N-glycopeptide enrichment strategies, and bioinformatic approaches to gain a better understanding of novel and glycosylated proteins in RJ. 24529077 5 71 theme RJ 773:774 arg1 proteins 776:783 RJ proteins 773:783 RJ proteins 773:783 RESULTS: A total of 25 N-glycosylated proteins, carrying 53 N-glycosylation sites, were identified in RJ proteins, of which 42 N-linked glycosylation sites were mapped as novel on RJ proteins. 24529077 0 72 from identification 14:27 arg1 jelly 82:86 royal jelly 76:86 royal jelly 76:86 Comprehensive identification of novel proteins and N-glycosylation sites in royal jelly. 24529077 5 73 theme N-glycosylation 731:745 arg1 sites 747:751 53 N-glycosylation sites 728:751 53 N-glycosylation sites 728:751 RESULTS: A total of 25 N-glycosylated proteins, carrying 53 N-glycosylation sites, were identified in RJ proteins, of which 42 N-linked glycosylation sites were mapped as novel on RJ proteins. 24529077 4 74 theme different 448:456 arg1 techniques 505:514 two different liquid chromatography-tandem mass spectrometry techniques 444:514 two different liquid chromatography-tandem mass spectrometry techniques 444:514 We used two different liquid chromatography-tandem mass spectrometry techniques, complementary N-glycopeptide enrichment strategies, and bioinformatic approaches to gain a better understanding of novel and glycosylated proteins in RJ. 24529077 8 75 theme engineering 1383:1393 arg1 approach 1395:1402 a genetic engineering approach 1373:1402 a genetic engineering approach 1373:1402 CONCLUSION: Our in-depth, large-scale mapping of novel glycosylation sites represents a crucial step toward systematically revealing the functionality of N-glycosylated RJ proteins, and is potentially useful for producing a protein with desirable pharmacokinetic and biological activity using a genetic engineering approach. 24529077 4 76 theme chromatography-tandem 465:485 arg1 spectrometry 492:503 liquid chromatography-tandem mass spectrometry 458:503 two different liquid chromatography-tandem mass spectrometry techniques 444:514 We used two different liquid chromatography-tandem mass spectrometry techniques, complementary N-glycopeptide enrichment strategies, and bioinformatic approaches to gain a better understanding of novel and glycosylated proteins in RJ. 24529077 3 77 theme further 413:419 arg1 investigation 421:433 further investigation 413:433 further investigation 413:433 However, some proteins remain unknown in RJ, and mapping N-glycosylation modification sites on RJ proteins demands further investigation. 24529077 5 78 theme N-linked 798:805 arg1 novel 842:846 novel 842:846 novel 842:846 RESULTS: A total of 25 N-glycosylated proteins, carrying 53 N-glycosylation sites, were identified in RJ proteins, of which 42 N-linked glycosylation sites were mapped as novel on RJ proteins. 24529077 5 78 theme N-linked 798:805 arg1 sites 821:825 42 N-linked glycosylation sites 795:825 42 N-linked glycosylation sites 795:825 RESULTS: A total of 25 N-glycosylated proteins, carrying 53 N-glycosylation sites, were identified in RJ proteins, of which 42 N-linked glycosylation sites were mapped as novel on RJ proteins. 24529077 3 79 theme mapping 347:353 arg1 sites 384:388 mapping N-glycosylation modification sites 347:388 mapping N-glycosylation modification sites on RJ proteins 347:403 However, some proteins remain unknown in RJ, and mapping N-glycosylation modification sites on RJ proteins demands further investigation. 24529077 5 80 gly N-glycosylation 731:745 arg2 53 728:729 53 728:729 53 728:729 RESULTS: A total of 25 N-glycosylated proteins, carrying 53 N-glycosylation sites, were identified in RJ proteins, of which 42 N-linked glycosylation sites were mapped as novel on RJ proteins. 24529077 5 80 gly N-glycosylation 731:745 arg2 sites 747:751 53 N-glycosylation sites 728:751 53 N-glycosylation sites 728:751 RESULTS: A total of 25 N-glycosylated proteins, carrying 53 N-glycosylation sites, were identified in RJ proteins, of which 42 N-linked glycosylation sites were mapped as novel on RJ proteins. 24529077 0 81 theme novel 32:36 arg1 proteins 38:45 novel proteins 32:45 novel proteins 32:45 Comprehensive identification of novel proteins and N-glycosylation sites in royal jelly. 24529077 8 82 theme in-depth 1096:1103 arg1 mapping 1118:1124 Our in-depth, large-scale mapping 1092:1124 Our in-depth, large-scale mapping of novel glycosylation sites 1092:1153 CONCLUSION: Our in-depth, large-scale mapping of novel glycosylation sites represents a crucial step toward systematically revealing the functionality of N-glycosylated RJ proteins, and is potentially useful for producing a protein with desirable pharmacokinetic and biological activity using a genetic engineering approach. 24529077 1 83 theme Royal 101:105 arg1 secretion 137:145 a proteinaceous secretion 121:145 a proteinaceous secretion produced from the hypopharyngeal and mandibular glands of nurse bees 121:214 BACKGROUND: Royal jelly (RJ) is a proteinaceous secretion produced from the hypopharyngeal and mandibular glands of nurse bees. 24529077 1 83 theme Royal 101:105 arg1 RJ 114:115 RJ 114:115 RJ 114:115 BACKGROUND: Royal jelly (RJ) is a proteinaceous secretion produced from the hypopharyngeal and mandibular glands of nurse bees. 24529077 1 83 theme Royal 101:105 arg1 BACKGROUND 89:98 BACKGROUND 89:98 BACKGROUND: Royal jelly (RJ) is a proteinaceous secretion produced from the hypopharyngeal and mandibular glands of nurse bees. 89:215 BACKGROUND: Royal jelly (RJ) is a proteinaceous secretion produced from the hypopharyngeal and mandibular glands of nurse bees. 24529077 1 83 theme Royal 101:105 arg1 jelly 107:111 Royal jelly 101:111 Royal jelly (RJ) 101:116 BACKGROUND: Royal jelly (RJ) is a proteinaceous secretion produced from the hypopharyngeal and mandibular glands of nurse bees. 24529077 10 84 theme innate 1563:1568 arg1 nature 1582:1587 the innate biochemical nature 1559:1587 the innate biochemical nature of RJ at both the proteome and glycoproteome levels 1559:1639 These findings contribute vital and new knowledge to our understanding of the innate biochemical nature of RJ at both the proteome and glycoproteome levels. 24529077 4 85 theme N-glycopeptide 531:544 arg1 strategies 557:566 complementary N-glycopeptide enrichment strategies 517:566 complementary N-glycopeptide enrichment strategies 517:566 We used two different liquid chromatography-tandem mass spectrometry techniques, complementary N-glycopeptide enrichment strategies, and bioinformatic approaches to gain a better understanding of novel and glycosylated proteins in RJ. 24529077 0 86 theme sites 67:71 arg1 identification 14:27 Comprehensive identification 0:27 Comprehensive identification of novel proteins and N-glycosylation sites in royal jelly. 0:87 Comprehensive identification of novel proteins and N-glycosylation sites in royal jelly. 24529077 3 87 theme modification 371:382 arg1 sites 384:388 mapping N-glycosylation modification sites 347:388 mapping N-glycosylation modification sites on RJ proteins 347:403 However, some proteins remain unknown in RJ, and mapping N-glycosylation modification sites on RJ proteins demands further investigation. 24529077 10 88 theme RJ 1592:1593 arg1 nature 1582:1587 the innate biochemical nature 1559:1587 the innate biochemical nature of RJ at both the proteome and glycoproteome levels 1559:1639 These findings contribute vital and new knowledge to our understanding of the innate biochemical nature of RJ at both the proteome and glycoproteome levels. 24529077 8 89 theme glycosylation 1135:1147 arg1 sites 1149:1153 novel glycosylation sites 1129:1153 novel glycosylation sites 1129:1153 CONCLUSION: Our in-depth, large-scale mapping of novel glycosylation sites represents a crucial step toward systematically revealing the functionality of N-glycosylated RJ proteins, and is potentially useful for producing a protein with desirable pharmacokinetic and biological activity using a genetic engineering approach. 24529077 10 90 theme nature 1582:1587 arg1 understanding 1542:1554 our understanding 1538:1554 our understanding of the innate biochemical nature of RJ at both the proteome and glycoproteome levels 1538:1639 These findings contribute vital and new knowledge to our understanding of the innate biochemical nature of RJ at both the proteome and glycoproteome levels. 24529077 9 91 theme proteome 1460:1467 arg1 coverage 1469:1476 the proteome coverage 1456:1476 the proteome coverage of RJ 1456:1482 The newly-identified proteins significantly extend the proteome coverage of RJ. 24529077 0 92 gly N-glycosylation 51:65 arg2 sites 67:71 N-glycosylation sites 51:71 N-glycosylation sites 51:71 Comprehensive identification of novel proteins and N-glycosylation sites in royal jelly. 24529077 10 93 theme proteome 1607:1614 arg1 levels 1634:1639 both the proteome and glycoproteome levels 1598:1639 levels 1634:1639 These findings contribute vital and new knowledge to our understanding of the innate biochemical nature of RJ at both the proteome and glycoproteome levels. 28196510 7 0 theme square 1392:1397 arg1 test 1399:1402 a chi square test 1386:1402 a chi square test 1386:1402 At respective False Positive Rate (FPR) cut-offs of 5% (p = 0.045), 10% (p = 0.016) and 20% (p = 0.005) for CXCR4 usage within the Geno2Pheno platform, HIV-1 subtype and viral tropism were significantly associated in a chi square test. 28196510 11 1 theme R5 1950:1951 arg1 isolates 1953:1960 R5 isolates 1950:1960 R5 isolates 1950:1960 R5 isolates had fewer PNGs than X4 isolates, but these differences were not significant except at position N262 (p = 0.040). 28196510 6 2 theme square 1063:1068 arg1 test 1070:1073 Chi square test 1059:1073 Chi square test 1059:1073 Chi square test was used to determine independent variables association and ANOVA applied on scale variables. 28196510 3 3 theme glycosylation 692:704 arg1 patterns 706:713 glycosylation patterns 692:713 glycosylation patterns 692:713 A total of 118 HIV env C2V3 sequence isolates generated previously from 59 Kenyan patients receiving highly active antiretroviral therapy (HAART) were examined for tropism and glycosylation patterns. 28196510 13 4 theme viral 2362:2366 arg1 associations 2321:2332 significant associations 2309:2332 significant associations of HIV-1 subtype diversity 2309:2359 These data reveal significant associations of HIV-1 subtype diversity, viral co-receptor tropism, viral suppression and envelope glycosylation. 28196510 13 4 theme viral 2362:2366 arg1 tropism 2380:2386 viral co-receptor tropism 2362:2386 viral co-receptor tropism 2362:2386 These data reveal significant associations of HIV-1 subtype diversity, viral co-receptor tropism, viral suppression and envelope glycosylation. 28196510 4 5 theme N-glycosite 876:886 arg1 tool 888:891 the N-glycosite tool 872:891 the N-glycosite tool within the Los Alamos Database 872:922 For analysis of Potential N-linked glycosylation sites (PNGs), amino acid sequences generated by the NCBI's Translate tool were applied to the HIVAlign and the N-glycosite tool within the Los Alamos Database. 28196510 4 6 link N-linked 742:749 arg1 PNGs 772:775 PNGs 772:775 PNGs 772:775 For analysis of Potential N-linked glycosylation sites (PNGs), amino acid sequences generated by the NCBI's Translate tool were applied to the HIVAlign and the N-glycosite tool within the Los Alamos Database. 28196510 4 6 link N-linked 742:749 arg1 sites 765:769 Potential N-linked glycosylation sites 732:769 Potential N-linked glycosylation sites (PNGs) 732:776 For analysis of Potential N-linked glycosylation sites (PNGs), amino acid sequences generated by the NCBI's Translate tool were applied to the HIVAlign and the N-glycosite tool within the Los Alamos Database. 28196510 3 7 theme sequence 544:551 arg1 isolates 553:560 118 HIV env C2V3 sequence isolates 527:560 118 HIV env C2V3 sequence isolates generated previously from 59 Kenyan patients receiving highly active antiretroviral therapy (HAART) 527:660 A total of 118 HIV env C2V3 sequence isolates generated previously from 59 Kenyan patients receiving highly active antiretroviral therapy (HAART) were examined for tropism and glycosylation patterns. 28196510 7 8 theme HIV-1 1321:1325 arg1 subtype 1327:1333 HIV-1 subtype 1321:1333 HIV-1 subtype 1321:1333 At respective False Positive Rate (FPR) cut-offs of 5% (p = 0.045), 10% (p = 0.016) and 20% (p = 0.005) for CXCR4 usage within the Geno2Pheno platform, HIV-1 subtype and viral tropism were significantly associated in a chi square test. 28196510 13 9 theme HIV-1 2337:2341 arg1 diversity 2351:2359 HIV-1 subtype diversity 2337:2359 HIV-1 subtype diversity 2337:2359 These data reveal significant associations of HIV-1 subtype diversity, viral co-receptor tropism, viral suppression and envelope glycosylation. 28196510 4 10 gly glycosylation 751:763 arg2 PNGs 772:775 PNGs 772:775 PNGs 772:775 For analysis of Potential N-linked glycosylation sites (PNGs), amino acid sequences generated by the NCBI's Translate tool were applied to the HIVAlign and the N-glycosite tool within the Los Alamos Database. 28196510 4 10 gly glycosylation 751:763 arg2 sites 765:769 Potential N-linked glycosylation sites 732:769 Potential N-linked glycosylation sites (PNGs) 732:776 For analysis of Potential N-linked glycosylation sites (PNGs), amino acid sequences generated by the NCBI's Translate tool were applied to the HIVAlign and the N-glycosite tool within the Los Alamos Database. 28196510 3 11 theme env 535:537 arg1 isolates 553:560 118 HIV env C2V3 sequence isolates 527:560 118 HIV env C2V3 sequence isolates generated previously from 59 Kenyan patients receiving highly active antiretroviral therapy (HAART) 527:660 A total of 118 HIV env C2V3 sequence isolates generated previously from 59 Kenyan patients receiving highly active antiretroviral therapy (HAART) were examined for tropism and glycosylation patterns. 28196510 13 12 theme diversity 2351:2359 arg1 suppression 2395:2405 viral suppression 2389:2405 viral suppression 2389:2405 These data reveal significant associations of HIV-1 subtype diversity, viral co-receptor tropism, viral suppression and envelope glycosylation. 28196510 13 12 theme diversity 2351:2359 arg1 glycosylation 2420:2432 envelope glycosylation 2411:2432 envelope glycosylation 2411:2432 These data reveal significant associations of HIV-1 subtype diversity, viral co-receptor tropism, viral suppression and envelope glycosylation. 28196510 13 12 theme diversity 2351:2359 arg1 tropism 2380:2386 viral co-receptor tropism 2362:2386 viral co-receptor tropism 2362:2386 These data reveal significant associations of HIV-1 subtype diversity, viral co-receptor tropism, viral suppression and envelope glycosylation. 28196510 13 12 theme diversity 2351:2359 arg1 associations 2321:2332 significant associations 2309:2332 significant associations of HIV-1 subtype diversity 2309:2359 These data reveal significant associations of HIV-1 subtype diversity, viral co-receptor tropism, viral suppression and envelope glycosylation. 28196510 4 13 gly N-glycosite 876:886 arg2 N-glycosite 876:886 N-glycosite 876:886 N-glycosite 876:886 For analysis of Potential N-linked glycosylation sites (PNGs), amino acid sequences generated by the NCBI's Translate tool were applied to the HIVAlign and the N-glycosite tool within the Los Alamos Database. 28196510 10 14 from positions 1809:1817 arg1 subtypes 1797:1804 subtypes 1797:1804 subtypes 1797:1804 The mean glycosylation density differed significantly between subtypes at positions, N277 (p = 0.034), N296 (p = 0.036), N302 (p = 0.034) and N366 (p = 0.004), with HIV-1D most heavily glycosylated of the subtypes. 28196510 0 15 theme genotypic 120:128 arg1 variability 130:140 viral genotypic variability 114:140 viral genotypic variability among Kenyan patients on HAART 114:171 Partial HIV C2V3 envelope sequence analysis reveals association of coreceptor tropism, envelope glycosylation and viral genotypic variability among Kenyan patients on HAART. 28196510 1 16 dep property 235:242 arg1 uses 247:250 uses 247:250 uses to subvert antiviral immunity and treatment 247:294 HIV-1 is highly variable genetically and at protein level, a property it uses to subvert antiviral immunity and treatment. 28196510 11 17 theme X4 1982:1983 arg1 isolates 1985:1992 X4 isolates 1982:1992 X4 isolates 1982:1992 R5 isolates had fewer PNGs than X4 isolates, but these differences were not significant except at position N262 (p = 0.040). 28196510 12 18 theme treatment 2204:2212 arg1 failures 2214:2221 virologic treatment failures 2194:2221 virologic treatment failures 2194:2221 Cell-associated isolates from virologic treatment success subjects were more glycosylated than cell-free isolates from virologic treatment failures both for the NXT (p = 0.016), and for all the patterns (p = 0.011). 28196510 2 19 theme co-receptor 422:432 arg1 tropism 434:440 co-receptor tropism 422:440 co-receptor tropism 422:440 The aim of this study was to assess if HIV subtype differences were associated with variations in glycosylation patterns and co-receptor tropism among HAART patients experiencing different virologic treatment outcomes. 28196510 1 20 theme protein 218:224 arg1 level 226:230 protein level 218:230 protein level 218:230 HIV-1 is highly variable genetically and at protein level, a property it uses to subvert antiviral immunity and treatment. 28196510 14 21 theme important 2459:2467 arg1 implications 2469:2480 important implications 2459:2480 important implications for designing therapy and vaccines against HIV 2459:2527 These associations have important implications for designing therapy and vaccines against HIV. 28196510 3 22 theme Kenyan 591:596 arg1 patients 598:605 59 Kenyan patients 588:605 59 Kenyan patients receiving highly active antiretroviral therapy (HAART) 588:660 A total of 118 HIV env C2V3 sequence isolates generated previously from 59 Kenyan patients receiving highly active antiretroviral therapy (HAART) were examined for tropism and glycosylation patterns. 28196510 4 23 theme Los 904:906 arg1 Database 915:922 the Los Alamos Database 900:922 the Los Alamos Database 900:922 For analysis of Potential N-linked glycosylation sites (PNGs), amino acid sequences generated by the NCBI's Translate tool were applied to the HIVAlign and the N-glycosite tool within the Los Alamos Database. 28196510 4 24 theme N-linked 742:749 arg1 PNGs 772:775 PNGs 772:775 PNGs 772:775 For analysis of Potential N-linked glycosylation sites (PNGs), amino acid sequences generated by the NCBI's Translate tool were applied to the HIVAlign and the N-glycosite tool within the Los Alamos Database. 28196510 4 24 theme N-linked 742:749 arg1 sites 765:769 Potential N-linked glycosylation sites 732:769 Potential N-linked glycosylation sites (PNGs) 732:776 For analysis of Potential N-linked glycosylation sites (PNGs), amino acid sequences generated by the NCBI's Translate tool were applied to the HIVAlign and the N-glycosite tool within the Los Alamos Database. 28196510 6 25 used used 1079:1082 arg2 test 1070:1073 Chi square test 1059:1073 Chi square test 1059:1073 Chi square test was used to determine independent variables association and ANOVA applied on scale variables. 28196510 5 26 theme Viral 925:929 arg1 tropism 931:937 Viral tropism 925:937 Viral tropism 925:937 Viral tropism was assessed using Geno2Pheno (G2P), WebPSSM and Phenoseq platforms as well as using Raymond's and Esbjörnsson's rules. 28196510 9 27 theme higher 1624:1629 arg1 proportions 1631:1641 higher proportions 1624:1641 higher proportions of X4 variants 1624:1656 Relative to other platforms used, Raymond's and Esbjörnsson's rules showed higher proportions of X4 variants, while WebPSSM resulted in lower proportions of X4 variants across subtypes. 28196510 7 28 theme % 1259:1259 arg1 cut-offs 1209:1216 cut-offs 1209:1216 cut-offs of 5% (p = 0.045), 10% (p = 0.016) and 20% (p = 0.005) for CXCR4 usage within the Geno2Pheno platform, HIV-1 subtype and viral tropism 1209:1351 At respective False Positive Rate (FPR) cut-offs of 5% (p = 0.045), 10% (p = 0.016) and 20% (p = 0.005) for CXCR4 usage within the Geno2Pheno platform, HIV-1 subtype and viral tropism were significantly associated in a chi square test. 28196510 3 29 theme active 624:629 arg1 HAART 655:659 HAART 655:659 HAART 655:659 A total of 118 HIV env C2V3 sequence isolates generated previously from 59 Kenyan patients receiving highly active antiretroviral therapy (HAART) were examined for tropism and glycosylation patterns. 28196510 3 29 theme active 624:629 arg1 therapy 646:652 highly active antiretroviral therapy 617:652 highly active antiretroviral therapy (HAART) 617:660 A total of 118 HIV env C2V3 sequence isolates generated previously from 59 Kenyan patients receiving highly active antiretroviral therapy (HAART) were examined for tropism and glycosylation patterns. 28196510 2 30 theme treatment 496:504 arg1 outcomes 506:513 different virologic treatment outcomes 476:513 different virologic treatment outcomes 476:513 The aim of this study was to assess if HIV subtype differences were associated with variations in glycosylation patterns and co-receptor tropism among HAART patients experiencing different virologic treatment outcomes. 28196510 12 31 theme virologic 2105:2113 arg1 subjects 2133:2140 virologic treatment success subjects 2105:2140 virologic treatment success subjects 2105:2140 Cell-associated isolates from virologic treatment success subjects were more glycosylated than cell-free isolates from virologic treatment failures both for the NXT (p = 0.016), and for all the patterns (p = 0.011). 28196510 0 32 theme tropism 78:84 arg1 association 52:62 association 52:62 association of coreceptor tropism, envelope glycosylation and viral genotypic variability among Kenyan patients on HAART 52:171 Partial HIV C2V3 envelope sequence analysis reveals association of coreceptor tropism, envelope glycosylation and viral genotypic variability among Kenyan patients on HAART. 28196510 9 33 theme variants 1649:1656 arg1 proportions 1631:1641 higher proportions 1624:1641 higher proportions of X4 variants 1624:1656 Relative to other platforms used, Raymond's and Esbjörnsson's rules showed higher proportions of X4 variants, while WebPSSM resulted in lower proportions of X4 variants across subtypes. 28196510 12 34 theme success 2125:2131 arg1 subjects 2133:2140 virologic treatment success subjects 2105:2140 virologic treatment success subjects 2105:2140 Cell-associated isolates from virologic treatment success subjects were more glycosylated than cell-free isolates from virologic treatment failures both for the NXT (p = 0.016), and for all the patterns (p = 0.011). 28196510 0 35 theme envelope 87:94 arg1 glycosylation 96:108 envelope glycosylation 87:108 envelope glycosylation 87:108 Partial HIV C2V3 envelope sequence analysis reveals association of coreceptor tropism, envelope glycosylation and viral genotypic variability among Kenyan patients on HAART. 28196510 7 36 theme viral 1339:1343 arg1 tropism 1345:1351 viral tropism 1339:1351 viral tropism 1339:1351 At respective False Positive Rate (FPR) cut-offs of 5% (p = 0.045), 10% (p = 0.016) and 20% (p = 0.005) for CXCR4 usage within the Geno2Pheno platform, HIV-1 subtype and viral tropism were significantly associated in a chi square test. 28196510 4 37 theme acid 785:788 arg1 sequences 790:798 amino acid sequences 779:798 amino acid sequences generated by the NCBI's Translate tool 779:837 For analysis of Potential N-linked glycosylation sites (PNGs), amino acid sequences generated by the NCBI's Translate tool were applied to the HIVAlign and the N-glycosite tool within the Los Alamos Database. 28196510 12 38 from subjects 2133:2140 arg1 isolates 2091:2098 Cell-associated isolates 2075:2098 Cell-associated isolates from virologic treatment success subjects 2075:2140 Cell-associated isolates from virologic treatment success subjects were more glycosylated than cell-free isolates from virologic treatment failures both for the NXT (p = 0.016), and for all the patterns (p = 0.011). 28196510 4 39 theme sites 765:769 arg1 analysis 720:727 analysis 720:727 analysis of Potential N-linked glycosylation sites (PNGs) 720:776 For analysis of Potential N-linked glycosylation sites (PNGs), amino acid sequences generated by the NCBI's Translate tool were applied to the HIVAlign and the N-glycosite tool within the Los Alamos Database. 28196510 13 40 theme envelope 2411:2418 arg1 glycosylation 2420:2432 envelope glycosylation 2411:2432 envelope glycosylation 2411:2432 These data reveal significant associations of HIV-1 subtype diversity, viral co-receptor tropism, viral suppression and envelope glycosylation. 28196510 13 40 theme envelope 2411:2418 arg1 associations 2321:2332 significant associations 2309:2332 significant associations of HIV-1 subtype diversity 2309:2359 These data reveal significant associations of HIV-1 subtype diversity, viral co-receptor tropism, viral suppression and envelope glycosylation. 28196510 0 41 theme Partial 0:6 arg1 sequence 26:33 Partial HIV C2V3 envelope sequence 0:33 Partial HIV C2V3 envelope sequence analysis 0:42 Partial HIV C2V3 envelope sequence analysis reveals association of coreceptor tropism, envelope glycosylation and viral genotypic variability among Kenyan patients on HAART. 28196510 1 42 theme antiviral 263:271 arg1 immunity 273:280 antiviral immunity 263:280 antiviral immunity 263:280 HIV-1 is highly variable genetically and at protein level, a property it uses to subvert antiviral immunity and treatment. 28196510 9 43 theme lower 1685:1689 arg1 proportions 1691:1701 lower proportions 1685:1701 lower proportions of X4 variants across subtypes 1685:1732 Relative to other platforms used, Raymond's and Esbjörnsson's rules showed higher proportions of X4 variants, while WebPSSM resulted in lower proportions of X4 variants across subtypes. 28196510 15 44 from progression 2617:2627 arg1 patients 2632:2639 patients 2632:2639 patients infected with these strains 2632:2667 Heavy glycosylation and preference for CXCR4 usage of HIV-1D may explain rapid disease progression in patients infected with these strains. 28196510 0 45 theme C2V3 12:15 arg1 sequence 26:33 Partial HIV C2V3 envelope sequence 0:33 Partial HIV C2V3 envelope sequence analysis 0:42 Partial HIV C2V3 envelope sequence analysis reveals association of coreceptor tropism, envelope glycosylation and viral genotypic variability among Kenyan patients on HAART. 28196510 2 46 theme different 476:484 arg1 outcomes 506:513 different virologic treatment outcomes 476:513 different virologic treatment outcomes 476:513 The aim of this study was to assess if HIV subtype differences were associated with variations in glycosylation patterns and co-receptor tropism among HAART patients experiencing different virologic treatment outcomes. 28196510 0 47 theme sequence 26:33 arg1 analysis 35:42 Partial HIV C2V3 envelope sequence analysis 0:42 Partial HIV C2V3 envelope sequence analysis 0:42 Partial HIV C2V3 envelope sequence analysis reveals association of coreceptor tropism, envelope glycosylation and viral genotypic variability among Kenyan patients on HAART. 28196510 13 48 theme viral 2389:2393 arg1 suppression 2395:2405 viral suppression 2389:2405 viral suppression 2389:2405 These data reveal significant associations of HIV-1 subtype diversity, viral co-receptor tropism, viral suppression and envelope glycosylation. 28196510 13 48 theme viral 2389:2393 arg1 associations 2321:2332 significant associations 2309:2332 significant associations of HIV-1 subtype diversity 2309:2359 These data reveal significant associations of HIV-1 subtype diversity, viral co-receptor tropism, viral suppression and envelope glycosylation. 28196510 9 49 theme variants 1709:1716 arg1 proportions 1691:1701 lower proportions 1685:1701 lower proportions of X4 variants across subtypes 1685:1732 Relative to other platforms used, Raymond's and Esbjörnsson's rules showed higher proportions of X4 variants, while WebPSSM resulted in lower proportions of X4 variants across subtypes. 28196510 15 50 theme CXCR4 2569:2573 arg1 usage 2575:2579 CXCR4 usage 2569:2579 CXCR4 usage of HIV-1D 2569:2589 Heavy glycosylation and preference for CXCR4 usage of HIV-1D may explain rapid disease progression in patients infected with these strains. 28196510 2 51 theme study 313:317 arg1 aim 301:303 The aim 297:303 The aim of this study 297:317 The aim of this study was to assess if HIV subtype differences were associated with variations in glycosylation patterns and co-receptor tropism among HAART patients experiencing different virologic treatment outcomes. 28196510 5 52 theme WebPSSM 976:982 arg1 platforms 997:1005 Geno2Pheno (G2P), WebPSSM and Phenoseq platforms 958:1005 Geno2Pheno (G2P), WebPSSM and Phenoseq platforms 958:1005 Viral tropism was assessed using Geno2Pheno (G2P), WebPSSM and Phenoseq platforms as well as using Raymond's and Esbjörnsson's rules. 28196510 10 53 theme glycosylation 1744:1756 arg1 density 1758:1764 The mean glycosylation density 1735:1764 The mean glycosylation density 1735:1764 The mean glycosylation density differed significantly between subtypes at positions, N277 (p = 0.034), N296 (p = 0.036), N302 (p = 0.034) and N366 (p = 0.004), with HIV-1D most heavily glycosylated of the subtypes. 28196510 2 54 theme subtype 340:346 arg1 differences 348:358 HIV subtype differences 336:358 HIV subtype differences 336:358 The aim of this study was to assess if HIV subtype differences were associated with variations in glycosylation patterns and co-receptor tropism among HAART patients experiencing different virologic treatment outcomes. 28196510 6 55 dep variables 1109:1117 arg1 variables 1109:1117 independent variables association and ANOVA 1097:1139 independent variables association and ANOVA applied on scale variables 1097:1166 Chi square test was used to determine independent variables association and ANOVA applied on scale variables. 28196510 6 55 dep variables 1109:1117 arg1 ANOVA 1135:1139 ANOVA 1135:1139 ANOVA 1135:1139 Chi square test was used to determine independent variables association and ANOVA applied on scale variables. 28196510 6 55 dep variables 1109:1117 arg1 association 1119:1129 association 1119:1129 association 1119:1129 Chi square test was used to determine independent variables association and ANOVA applied on scale variables. 28196510 7 56 theme chi 1388:1390 arg1 test 1399:1402 a chi square test 1386:1402 a chi square test 1386:1402 At respective False Positive Rate (FPR) cut-offs of 5% (p = 0.045), 10% (p = 0.016) and 20% (p = 0.005) for CXCR4 usage within the Geno2Pheno platform, HIV-1 subtype and viral tropism were significantly associated in a chi square test. 28196510 5 57 theme Phenoseq 988:995 arg1 platforms 997:1005 Geno2Pheno (G2P), WebPSSM and Phenoseq platforms 958:1005 Geno2Pheno (G2P), WebPSSM and Phenoseq platforms 958:1005 Viral tropism was assessed using Geno2Pheno (G2P), WebPSSM and Phenoseq platforms as well as using Raymond's and Esbjörnsson's rules. 28196510 15 58 theme Heavy 2530:2534 arg1 glycosylation 2536:2548 Heavy glycosylation 2530:2548 Heavy glycosylation 2530:2548 Heavy glycosylation and preference for CXCR4 usage of HIV-1D may explain rapid disease progression in patients infected with these strains. 28196510 13 59 theme subtype 2343:2349 arg1 diversity 2351:2359 HIV-1 subtype diversity 2337:2359 HIV-1 subtype diversity 2337:2359 These data reveal significant associations of HIV-1 subtype diversity, viral co-receptor tropism, viral suppression and envelope glycosylation. 28196510 6 60 theme Chi 1059:1061 arg1 test 1070:1073 Chi square test 1059:1073 Chi square test 1059:1073 Chi square test was used to determine independent variables association and ANOVA applied on scale variables. 28196510 8 61 theme significant 1495:1505 arg1 associations 1507:1518 significant associations 1495:1518 significant associations between subtype and tropism 1495:1546 Raymond's rule (p = 0.024) and WebPSSM (p = 0.05), but not Phenoseq or Esbjörnsson showed significant associations between subtype and tropism. 28196510 13 62 theme co-receptor 2368:2378 arg1 associations 2321:2332 significant associations 2309:2332 significant associations of HIV-1 subtype diversity 2309:2359 These data reveal significant associations of HIV-1 subtype diversity, viral co-receptor tropism, viral suppression and envelope glycosylation. 28196510 13 62 theme co-receptor 2368:2378 arg1 tropism 2380:2386 viral co-receptor tropism 2362:2386 viral co-receptor tropism 2362:2386 These data reveal significant associations of HIV-1 subtype diversity, viral co-receptor tropism, viral suppression and envelope glycosylation. 28196510 3 63 theme C2V3 539:542 arg1 isolates 553:560 118 HIV env C2V3 sequence isolates 527:560 118 HIV env C2V3 sequence isolates generated previously from 59 Kenyan patients receiving highly active antiretroviral therapy (HAART) 527:660 A total of 118 HIV env C2V3 sequence isolates generated previously from 59 Kenyan patients receiving highly active antiretroviral therapy (HAART) were examined for tropism and glycosylation patterns. 28196510 6 64 theme scale 1152:1156 arg1 variables 1158:1166 scale variables 1152:1166 scale variables 1152:1166 Chi square test was used to determine independent variables association and ANOVA applied on scale variables. 28196510 0 65 from patients 155:162 arg1 HAART 167:171 HAART 167:171 HAART 167:171 Partial HIV C2V3 envelope sequence analysis reveals association of coreceptor tropism, envelope glycosylation and viral genotypic variability among Kenyan patients on HAART. 28196510 3 66 theme HIV 531:533 arg1 isolates 553:560 118 HIV env C2V3 sequence isolates 527:560 118 HIV env C2V3 sequence isolates generated previously from 59 Kenyan patients receiving highly active antiretroviral therapy (HAART) 527:660 A total of 118 HIV env C2V3 sequence isolates generated previously from 59 Kenyan patients receiving highly active antiretroviral therapy (HAART) were examined for tropism and glycosylation patterns. 28196510 9 67 theme other 1561:1565 arg1 platforms 1567:1575 other platforms 1561:1575 other platforms used 1561:1580 Relative to other platforms used, Raymond's and Esbjörnsson's rules showed higher proportions of X4 variants, while WebPSSM resulted in lower proportions of X4 variants across subtypes. 28196510 11 68 contain had 1962:1964 arg1 isolates 1953:1960 R5 isolates 1950:1960 R5 isolates 1950:1960 R5 isolates had fewer PNGs than X4 isolates, but these differences were not significant except at position N262 (p = 0.040). 28196510 11 68 contain had 1962:1964 arg2 PNGs 1972:1975 fewer PNGs 1966:1975 fewer PNGs 1966:1975 R5 isolates had fewer PNGs than X4 isolates, but these differences were not significant except at position N262 (p = 0.040). 28196510 2 69 theme virologic 486:494 arg1 outcomes 506:513 different virologic treatment outcomes 476:513 different virologic treatment outcomes 476:513 The aim of this study was to assess if HIV subtype differences were associated with variations in glycosylation patterns and co-receptor tropism among HAART patients experiencing different virologic treatment outcomes. 28196510 12 70 from failures 2214:2221 arg1 isolates 2180:2187 cell-free isolates 2170:2187 cell-free isolates from virologic treatment failures 2170:2221 Cell-associated isolates from virologic treatment success subjects were more glycosylated than cell-free isolates from virologic treatment failures both for the NXT (p = 0.016), and for all the patterns (p = 0.011). 28196510 11 71 theme fewer 1966:1970 arg1 PNGs 1972:1975 fewer PNGs 1966:1975 fewer PNGs 1966:1975 R5 isolates had fewer PNGs than X4 isolates, but these differences were not significant except at position N262 (p = 0.040). 28196510 15 72 theme rapid 2603:2607 arg1 progression 2617:2627 rapid disease progression 2603:2627 rapid disease progression in patients infected with these strains 2603:2667 Heavy glycosylation and preference for CXCR4 usage of HIV-1D may explain rapid disease progression in patients infected with these strains. 28196510 0 73 theme variability 130:140 arg1 association 52:62 association 52:62 association of coreceptor tropism, envelope glycosylation and viral genotypic variability among Kenyan patients on HAART 52:171 Partial HIV C2V3 envelope sequence analysis reveals association of coreceptor tropism, envelope glycosylation and viral genotypic variability among Kenyan patients on HAART. 28196510 3 74 theme isolates 553:560 arg1 total 518:522 A total 516:522 A total of 118 HIV env C2V3 sequence isolates generated previously from 59 Kenyan patients receiving highly active antiretroviral therapy (HAART) 516:660 A total of 118 HIV env C2V3 sequence isolates generated previously from 59 Kenyan patients receiving highly active antiretroviral therapy (HAART) were examined for tropism and glycosylation patterns. 28196510 4 75 theme Alamos 908:913 arg1 Database 915:922 the Los Alamos Database 900:922 the Los Alamos Database 900:922 For analysis of Potential N-linked glycosylation sites (PNGs), amino acid sequences generated by the NCBI's Translate tool were applied to the HIVAlign and the N-glycosite tool within the Los Alamos Database. 28196510 7 76 theme Geno2Pheno 1300:1309 arg1 platform 1311:1318 the Geno2Pheno platform 1296:1318 the Geno2Pheno platform 1296:1318 At respective False Positive Rate (FPR) cut-offs of 5% (p = 0.045), 10% (p = 0.016) and 20% (p = 0.005) for CXCR4 usage within the Geno2Pheno platform, HIV-1 subtype and viral tropism were significantly associated in a chi square test. 28196510 0 77 theme Kenyan 148:153 arg1 patients 155:162 Kenyan patients 148:162 Kenyan patients on HAART 148:171 Partial HIV C2V3 envelope sequence analysis reveals association of coreceptor tropism, envelope glycosylation and viral genotypic variability among Kenyan patients on HAART. 28196510 12 78 gly glycosylated 2152:2163 arg1 isolates 2091:2098 Cell-associated isolates 2075:2098 Cell-associated isolates from virologic treatment success subjects 2075:2140 Cell-associated isolates from virologic treatment success subjects were more glycosylated than cell-free isolates from virologic treatment failures both for the NXT (p = 0.016), and for all the patterns (p = 0.011). 28196510 12 79 theme virologic 2194:2202 arg1 failures 2214:2221 virologic treatment failures 2194:2221 virologic treatment failures 2194:2221 Cell-associated isolates from virologic treatment success subjects were more glycosylated than cell-free isolates from virologic treatment failures both for the NXT (p = 0.016), and for all the patterns (p = 0.011). 28196510 7 80 theme respective 1172:1181 arg1 Rate 1198:1201 respective False Positive Rate 1172:1201 respective False Positive Rate (FPR) 1172:1207 At respective False Positive Rate (FPR) cut-offs of 5% (p = 0.045), 10% (p = 0.016) and 20% (p = 0.005) for CXCR4 usage within the Geno2Pheno platform, HIV-1 subtype and viral tropism were significantly associated in a chi square test. 28196510 7 80 theme respective 1172:1181 arg1 FPR 1204:1206 FPR 1204:1206 FPR 1204:1206 At respective False Positive Rate (FPR) cut-offs of 5% (p = 0.045), 10% (p = 0.016) and 20% (p = 0.005) for CXCR4 usage within the Geno2Pheno platform, HIV-1 subtype and viral tropism were significantly associated in a chi square test. 28196510 7 81 theme CXCR4 1277:1281 arg1 usage 1283:1287 CXCR4 usage 1277:1287 CXCR4 usage within the Geno2Pheno platform 1277:1318 At respective False Positive Rate (FPR) cut-offs of 5% (p = 0.045), 10% (p = 0.016) and 20% (p = 0.005) for CXCR4 usage within the Geno2Pheno platform, HIV-1 subtype and viral tropism were significantly associated in a chi square test. 28196510 3 82 theme antiretroviral 631:644 arg1 HAART 655:659 HAART 655:659 HAART 655:659 A total of 118 HIV env C2V3 sequence isolates generated previously from 59 Kenyan patients receiving highly active antiretroviral therapy (HAART) were examined for tropism and glycosylation patterns. 28196510 3 82 theme antiretroviral 631:644 arg1 therapy 646:652 highly active antiretroviral therapy 617:652 highly active antiretroviral therapy (HAART) 617:660 A total of 118 HIV env C2V3 sequence isolates generated previously from 59 Kenyan patients receiving highly active antiretroviral therapy (HAART) were examined for tropism and glycosylation patterns. 28196510 4 83 theme Potential 732:740 arg1 PNGs 772:775 PNGs 772:775 PNGs 772:775 For analysis of Potential N-linked glycosylation sites (PNGs), amino acid sequences generated by the NCBI's Translate tool were applied to the HIVAlign and the N-glycosite tool within the Los Alamos Database. 28196510 4 83 theme Potential 732:740 arg1 sites 765:769 Potential N-linked glycosylation sites 732:769 Potential N-linked glycosylation sites (PNGs) 732:776 For analysis of Potential N-linked glycosylation sites (PNGs), amino acid sequences generated by the NCBI's Translate tool were applied to the HIVAlign and the N-glycosite tool within the Los Alamos Database. 28196510 0 84 theme coreceptor 67:76 arg1 tropism 78:84 coreceptor tropism 67:84 coreceptor tropism 67:84 Partial HIV C2V3 envelope sequence analysis reveals association of coreceptor tropism, envelope glycosylation and viral genotypic variability among Kenyan patients on HAART. 28196510 12 85 theme treatment 2115:2123 arg1 subjects 2133:2140 virologic treatment success subjects 2105:2140 virologic treatment success subjects 2105:2140 Cell-associated isolates from virologic treatment success subjects were more glycosylated than cell-free isolates from virologic treatment failures both for the NXT (p = 0.016), and for all the patterns (p = 0.011). 28196510 14 86 contain have 2454:2457 arg1 associations 2441:2452 These associations 2435:2452 These associations 2435:2452 These associations have important implications for designing therapy and vaccines against HIV. 28196510 14 86 contain have 2454:2457 arg2 implications 2469:2480 important implications 2459:2480 important implications for designing therapy and vaccines against HIV 2459:2527 These associations have important implications for designing therapy and vaccines against HIV. 28196510 7 87 theme False 1183:1187 arg1 Rate 1198:1201 respective False Positive Rate 1172:1201 respective False Positive Rate (FPR) 1172:1207 At respective False Positive Rate (FPR) cut-offs of 5% (p = 0.045), 10% (p = 0.016) and 20% (p = 0.005) for CXCR4 usage within the Geno2Pheno platform, HIV-1 subtype and viral tropism were significantly associated in a chi square test. 28196510 7 87 theme False 1183:1187 arg1 FPR 1204:1206 FPR 1204:1206 FPR 1204:1206 At respective False Positive Rate (FPR) cut-offs of 5% (p = 0.045), 10% (p = 0.016) and 20% (p = 0.005) for CXCR4 usage within the Geno2Pheno platform, HIV-1 subtype and viral tropism were significantly associated in a chi square test. 28196510 7 88 theme Positive 1189:1196 arg1 Rate 1198:1201 respective False Positive Rate 1172:1201 respective False Positive Rate (FPR) 1172:1207 At respective False Positive Rate (FPR) cut-offs of 5% (p = 0.045), 10% (p = 0.016) and 20% (p = 0.005) for CXCR4 usage within the Geno2Pheno platform, HIV-1 subtype and viral tropism were significantly associated in a chi square test. 28196510 7 88 theme Positive 1189:1196 arg1 FPR 1204:1206 FPR 1204:1206 FPR 1204:1206 At respective False Positive Rate (FPR) cut-offs of 5% (p = 0.045), 10% (p = 0.016) and 20% (p = 0.005) for CXCR4 usage within the Geno2Pheno platform, HIV-1 subtype and viral tropism were significantly associated in a chi square test. 28196510 9 89 theme X4 1646:1647 arg1 variants 1649:1656 X4 variants 1646:1656 X4 variants 1646:1656 Relative to other platforms used, Raymond's and Esbjörnsson's rules showed higher proportions of X4 variants, while WebPSSM resulted in lower proportions of X4 variants across subtypes. 28196510 0 90 theme glycosylation 96:108 arg1 association 52:62 association 52:62 association of coreceptor tropism, envelope glycosylation and viral genotypic variability among Kenyan patients on HAART 52:171 Partial HIV C2V3 envelope sequence analysis reveals association of coreceptor tropism, envelope glycosylation and viral genotypic variability among Kenyan patients on HAART. 28196510 12 91 theme Cell-associated 2075:2089 arg1 isolates 2091:2098 Cell-associated isolates 2075:2098 Cell-associated isolates from virologic treatment success subjects 2075:2140 Cell-associated isolates from virologic treatment success subjects were more glycosylated than cell-free isolates from virologic treatment failures both for the NXT (p = 0.016), and for all the patterns (p = 0.011). 28196510 10 92 gly glycosylated 1920:1931 arg1 HIV-1D 1900:1905 HIV-1D 1900:1905 HIV-1D most heavily glycosylated of the subtypes 1900:1947 The mean glycosylation density differed significantly between subtypes at positions, N277 (p = 0.034), N296 (p = 0.036), N302 (p = 0.034) and N366 (p = 0.004), with HIV-1D most heavily glycosylated of the subtypes. 28196510 0 93 theme viral 114:118 arg1 variability 130:140 viral genotypic variability 114:140 viral genotypic variability among Kenyan patients on HAART 114:171 Partial HIV C2V3 envelope sequence analysis reveals association of coreceptor tropism, envelope glycosylation and viral genotypic variability among Kenyan patients on HAART. 28196510 5 94 theme G2P 970:972 arg1 platforms 997:1005 Geno2Pheno (G2P), WebPSSM and Phenoseq platforms 958:1005 Geno2Pheno (G2P), WebPSSM and Phenoseq platforms 958:1005 Viral tropism was assessed using Geno2Pheno (G2P), WebPSSM and Phenoseq platforms as well as using Raymond's and Esbjörnsson's rules. 28196510 10 95 with subtypes 1797:1804 arg1 HIV-1D 1900:1905 HIV-1D 1900:1905 HIV-1D most heavily glycosylated of the subtypes 1900:1947 The mean glycosylation density differed significantly between subtypes at positions, N277 (p = 0.034), N296 (p = 0.036), N302 (p = 0.034) and N366 (p = 0.004), with HIV-1D most heavily glycosylated of the subtypes. 28196510 4 96 theme amino 779:783 arg1 sequences 790:798 amino acid sequences 779:798 amino acid sequences generated by the NCBI's Translate tool 779:837 For analysis of Potential N-linked glycosylation sites (PNGs), amino acid sequences generated by the NCBI's Translate tool were applied to the HIVAlign and the N-glycosite tool within the Los Alamos Database. 28196510 0 97 theme HIV 8:10 arg1 sequence 26:33 Partial HIV C2V3 envelope sequence 0:33 Partial HIV C2V3 envelope sequence analysis 0:42 Partial HIV C2V3 envelope sequence analysis reveals association of coreceptor tropism, envelope glycosylation and viral genotypic variability among Kenyan patients on HAART. 28196510 13 98 theme significant 2309:2319 arg1 suppression 2395:2405 viral suppression 2389:2405 viral suppression 2389:2405 These data reveal significant associations of HIV-1 subtype diversity, viral co-receptor tropism, viral suppression and envelope glycosylation. 28196510 13 98 theme significant 2309:2319 arg1 glycosylation 2420:2432 envelope glycosylation 2411:2432 envelope glycosylation 2411:2432 These data reveal significant associations of HIV-1 subtype diversity, viral co-receptor tropism, viral suppression and envelope glycosylation. 28196510 13 98 theme significant 2309:2319 arg1 tropism 2380:2386 viral co-receptor tropism 2362:2386 viral co-receptor tropism 2362:2386 These data reveal significant associations of HIV-1 subtype diversity, viral co-receptor tropism, viral suppression and envelope glycosylation. 28196510 13 98 theme significant 2309:2319 arg1 associations 2321:2332 significant associations 2309:2332 significant associations of HIV-1 subtype diversity 2309:2359 These data reveal significant associations of HIV-1 subtype diversity, viral co-receptor tropism, viral suppression and envelope glycosylation. 28196510 11 99 from position 2048:2055 arg1 significant 2026:2036 significant 2026:2036 significant 2026:2036 R5 isolates had fewer PNGs than X4 isolates, but these differences were not significant except at position N262 (p = 0.040). 28196510 4 100 theme glycosylation 751:763 arg1 PNGs 772:775 PNGs 772:775 PNGs 772:775 For analysis of Potential N-linked glycosylation sites (PNGs), amino acid sequences generated by the NCBI's Translate tool were applied to the HIVAlign and the N-glycosite tool within the Los Alamos Database. 28196510 4 100 theme glycosylation 751:763 arg1 sites 765:769 Potential N-linked glycosylation sites 732:769 Potential N-linked glycosylation sites (PNGs) 732:776 For analysis of Potential N-linked glycosylation sites (PNGs), amino acid sequences generated by the NCBI's Translate tool were applied to the HIVAlign and the N-glycosite tool within the Los Alamos Database. 28196510 12 101 theme cell-free 2170:2178 arg1 isolates 2180:2187 cell-free isolates 2170:2187 cell-free isolates from virologic treatment failures 2170:2221 Cell-associated isolates from virologic treatment success subjects were more glycosylated than cell-free isolates from virologic treatment failures both for the NXT (p = 0.016), and for all the patterns (p = 0.011). 28196510 0 102 theme envelope 17:24 arg1 sequence 26:33 Partial HIV C2V3 envelope sequence 0:33 Partial HIV C2V3 envelope sequence analysis 0:42 Partial HIV C2V3 envelope sequence analysis reveals association of coreceptor tropism, envelope glycosylation and viral genotypic variability among Kenyan patients on HAART. 28196510 7 103 theme % 1239:1239 arg1 cut-offs 1209:1216 cut-offs 1209:1216 cut-offs of 5% (p = 0.045), 10% (p = 0.016) and 20% (p = 0.005) for CXCR4 usage within the Geno2Pheno platform, HIV-1 subtype and viral tropism 1209:1351 At respective False Positive Rate (FPR) cut-offs of 5% (p = 0.045), 10% (p = 0.016) and 20% (p = 0.005) for CXCR4 usage within the Geno2Pheno platform, HIV-1 subtype and viral tropism were significantly associated in a chi square test. 28196510 10 104 theme mean 1739:1742 arg1 density 1758:1764 The mean glycosylation density 1735:1764 The mean glycosylation density 1735:1764 The mean glycosylation density differed significantly between subtypes at positions, N277 (p = 0.034), N296 (p = 0.036), N302 (p = 0.034) and N366 (p = 0.004), with HIV-1D most heavily glycosylated of the subtypes. 28196510 2 105 theme glycosylation 395:407 arg1 patterns 409:416 glycosylation patterns 395:416 glycosylation patterns 395:416 The aim of this study was to assess if HIV subtype differences were associated with variations in glycosylation patterns and co-receptor tropism among HAART patients experiencing different virologic treatment outcomes. 28196510 15 106 theme disease 2609:2615 arg1 progression 2617:2627 rapid disease progression 2603:2627 rapid disease progression in patients infected with these strains 2603:2667 Heavy glycosylation and preference for CXCR4 usage of HIV-1D may explain rapid disease progression in patients infected with these strains. 28196510 9 107 theme X4 1706:1707 arg1 variants 1709:1716 X4 variants 1706:1716 X4 variants across subtypes 1706:1732 Relative to other platforms used, Raymond's and Esbjörnsson's rules showed higher proportions of X4 variants, while WebPSSM resulted in lower proportions of X4 variants across subtypes. 28196510 15 108 theme HIV-1D 2584:2589 arg1 usage 2575:2579 CXCR4 usage 2569:2579 CXCR4 usage of HIV-1D 2569:2589 Heavy glycosylation and preference for CXCR4 usage of HIV-1D may explain rapid disease progression in patients infected with these strains. 28196510 6 109 theme independent 1097:1107 arg1 variables 1109:1117 independent variables association and ANOVA 1097:1139 independent variables association and ANOVA applied on scale variables 1097:1166 Chi square test was used to determine independent variables association and ANOVA applied on scale variables. 28196510 6 109 theme independent 1097:1107 arg1 ANOVA 1135:1139 ANOVA 1135:1139 ANOVA 1135:1139 Chi square test was used to determine independent variables association and ANOVA applied on scale variables. 28196510 6 109 theme independent 1097:1107 arg1 association 1119:1129 association 1119:1129 association 1119:1129 Chi square test was used to determine independent variables association and ANOVA applied on scale variables. 28196510 2 110 theme HAART 448:452 arg1 patients 454:461 HAART patients 448:461 HAART patients experiencing different virologic treatment outcomes 448:513 The aim of this study was to assess if HIV subtype differences were associated with variations in glycosylation patterns and co-receptor tropism among HAART patients experiencing different virologic treatment outcomes. 28196510 4 111 theme Translate 824:832 arg1 tool 834:837 the NCBI's Translate tool 813:837 the NCBI's Translate tool 813:837 For analysis of Potential N-linked glycosylation sites (PNGs), amino acid sequences generated by the NCBI's Translate tool were applied to the HIVAlign and the N-glycosite tool within the Los Alamos Database. 28196510 7 112 theme % 1222:1222 arg1 cut-offs 1209:1216 cut-offs 1209:1216 cut-offs of 5% (p = 0.045), 10% (p = 0.016) and 20% (p = 0.005) for CXCR4 usage within the Geno2Pheno platform, HIV-1 subtype and viral tropism 1209:1351 At respective False Positive Rate (FPR) cut-offs of 5% (p = 0.045), 10% (p = 0.016) and 20% (p = 0.005) for CXCR4 usage within the Geno2Pheno platform, HIV-1 subtype and viral tropism were significantly associated in a chi square test. 28196510 2 113 from variations 381:390 arg1 tropism 434:440 co-receptor tropism 422:440 co-receptor tropism 422:440 The aim of this study was to assess if HIV subtype differences were associated with variations in glycosylation patterns and co-receptor tropism among HAART patients experiencing different virologic treatment outcomes. 28196510 2 113 from variations 381:390 arg1 patterns 409:416 glycosylation patterns 395:416 glycosylation patterns 395:416 The aim of this study was to assess if HIV subtype differences were associated with variations in glycosylation patterns and co-receptor tropism among HAART patients experiencing different virologic treatment outcomes. 28196510 2 114 theme HIV 336:338 arg1 differences 348:358 HIV subtype differences 336:358 HIV subtype differences 336:358 The aim of this study was to assess if HIV subtype differences were associated with variations in glycosylation patterns and co-receptor tropism among HAART patients experiencing different virologic treatment outcomes. 25751231 7 0 theme available 1503:1511 arg1 structures 1513:1522 the available structures 1499:1522 the available structures of gp120 alone and in complex with CD4 and various nMAbs 1499:1579 Structural analysis based on the available structures of gp120 alone and in complex with CD4 and various nMAbs elucidates a molecular rationale for this experimental observation. 25751231 4 1 theme HIV-1 890:894 arg1 donors 905:910 HIV-1 positive donors 890:910 HIV-1 positive donors 890:910 The effects were then evaluated by examining infectivity and sensitivity to antibody-mediated neutralization by neutralizing monoclonal antibodies (nMAbs) and serum antibodies from HIV-1 positive donors. 25751231 3 2 theme selected 675:682 arg1 mutants 700:706 selected individual PNGS mutants 675:706 selected individual PNGS mutants 675:706 To further understand the functional role of these PNGS, we generated double and multiple mutants from selected individual PNGS mutants. 25751231 8 3 theme better 1869:1874 arg1 understanding 1876:1888 a better understanding 1867:1888 a better understanding of the interplay between HIV-1 and VRC01/03 1867:1932 CONCLUSIONS: The data indicate that N463 plays an important role in regulating the CD4bs MAbs VRC01/VRC03 sensitivity in the genetic background of N197D mutation of gp120, which should provide valuable information for a better understanding of the interplay between HIV-1 and VRC01/03. 25751231 1 4 theme correct 247:253 arg1 folding 255:261 correct folding 247:261 correct folding 247:261 BACKGROUND: HIV-1 gp120/gp41 is heavily modified by n-linked carbohydrates that play important roles either in correct folding or in shielding vulnerable viral protein surfaces from antibody recognition. 25751231 8 5 theme interplay 1897:1905 arg1 understanding 1876:1888 a better understanding 1867:1888 a better understanding of the interplay between HIV-1 and VRC01/03 1867:1932 CONCLUSIONS: The data indicate that N463 plays an important role in regulating the CD4bs MAbs VRC01/VRC03 sensitivity in the genetic background of N197D mutation of gp120, which should provide valuable information for a better understanding of the interplay between HIV-1 and VRC01/03. 25751231 6 6 theme anti-CD4bs 1440:1449 arg1 VRC01/VRC03 1457:1467 the anti-CD4bs nMAbs VRC01/VRC03 1436:1467 the anti-CD4bs nMAbs VRC01/VRC03 1436:1467 In terms of neutralization sensitivity to known nMAbs, we found that adding N463Q mutation to all the gp120 mutants containing N197D significantly increased neutralization sensitivity to VRC01 and VRC03, suggesting N197 and N463 have a strong synergistic effect in regulating the neutralizing sensitivity of HIV-1 to the anti-CD4bs nMAbs VRC01/VRC03. 25751231 8 7 theme CD4bs 1732:1736 arg1 sensitivity 1755:1765 the CD4bs MAbs VRC01/VRC03 sensitivity 1728:1765 the CD4bs MAbs VRC01/VRC03 sensitivity 1728:1765 CONCLUSIONS: The data indicate that N463 plays an important role in regulating the CD4bs MAbs VRC01/VRC03 sensitivity in the genetic background of N197D mutation of gp120, which should provide valuable information for a better understanding of the interplay between HIV-1 and VRC01/03. 25751231 6 8 theme known 1161:1165 arg1 nMAbs 1167:1171 known nMAbs 1161:1171 known nMAbs 1161:1171 In terms of neutralization sensitivity to known nMAbs, we found that adding N463Q mutation to all the gp120 mutants containing N197D significantly increased neutralization sensitivity to VRC01 and VRC03, suggesting N197 and N463 have a strong synergistic effect in regulating the neutralizing sensitivity of HIV-1 to the anti-CD4bs nMAbs VRC01/VRC03. 25751231 8 9 theme VRC01/VRC03 1743:1753 arg1 sensitivity 1755:1765 the CD4bs MAbs VRC01/VRC03 sensitivity 1728:1765 the CD4bs MAbs VRC01/VRC03 sensitivity 1728:1765 CONCLUSIONS: The data indicate that N463 plays an important role in regulating the CD4bs MAbs VRC01/VRC03 sensitivity in the genetic background of N197D mutation of gp120, which should provide valuable information for a better understanding of the interplay between HIV-1 and VRC01/03. 25751231 6 10 theme sensitivity 1146:1156 arg1 terms 1122:1126 terms 1122:1126 terms of neutralization sensitivity to known nMAbs 1122:1171 In terms of neutralization sensitivity to known nMAbs, we found that adding N463Q mutation to all the gp120 mutants containing N197D significantly increased neutralization sensitivity to VRC01 and VRC03, suggesting N197 and N463 have a strong synergistic effect in regulating the neutralizing sensitivity of HIV-1 to the anti-CD4bs nMAbs VRC01/VRC03. 25751231 0 11 theme Neutralizing 91:102 arg1 Antibodies 115:124 Neutralizing Monoclonal Antibodies VRC01/03 91:133 Neutralizing Monoclonal Antibodies VRC01/03 91:133 N463 Glycosylation Site on V5 Loop of a Mutant gp120 Regulates the Sensitivity of HIV-1 to Neutralizing Monoclonal Antibodies VRC01/03. 25751231 7 12 with complex 1546:1552 arg1 CD4 1559:1561 CD4 1559:1561 CD4 1559:1561 Structural analysis based on the available structures of gp120 alone and in complex with CD4 and various nMAbs elucidates a molecular rationale for this experimental observation. 25751231 7 12 with complex 1546:1552 arg1 nMAbs 1575:1579 various nMAbs 1567:1579 various nMAbs 1567:1579 Structural analysis based on the available structures of gp120 alone and in complex with CD4 and various nMAbs elucidates a molecular rationale for this experimental observation. 25751231 1 13 theme n-linked 188:195 arg1 carbohydrates 197:209 n-linked carbohydrates 188:209 n-linked carbohydrates that play important roles either in correct folding or in shielding vulnerable viral protein surfaces from antibody recognition 188:337 BACKGROUND: HIV-1 gp120/gp41 is heavily modified by n-linked carbohydrates that play important roles either in correct folding or in shielding vulnerable viral protein surfaces from antibody recognition. 25751231 6 14 theme gp120 1221:1225 arg1 mutants 1227:1233 all the gp120 mutants 1213:1233 all the gp120 mutants containing N197D 1213:1250 In terms of neutralization sensitivity to known nMAbs, we found that adding N463Q mutation to all the gp120 mutants containing N197D significantly increased neutralization sensitivity to VRC01 and VRC03, suggesting N197 and N463 have a strong synergistic effect in regulating the neutralizing sensitivity of HIV-1 to the anti-CD4bs nMAbs VRC01/VRC03. 25751231 3 15 theme functional 598:607 arg1 role 609:612 the functional role 594:612 the functional role of these PNGS 594:626 To further understand the functional role of these PNGS, we generated double and multiple mutants from selected individual PNGS mutants. 25751231 8 16 theme genetic 1774:1780 arg1 background 1782:1791 the genetic background 1770:1791 the genetic background of N197D mutation of gp120, which should provide valuable information for a better understanding of the interplay between HIV-1 and VRC01/03 1770:1932 CONCLUSIONS: The data indicate that N463 plays an important role in regulating the CD4bs MAbs VRC01/VRC03 sensitivity in the genetic background of N197D mutation of gp120, which should provide valuable information for a better understanding of the interplay between HIV-1 and VRC01/03. 25751231 3 17 from mutants 700:706 arg1 mutants 662:668 double and multiple mutants 642:668 double and multiple mutants from selected individual PNGS mutants 642:706 To further understand the functional role of these PNGS, we generated double and multiple mutants from selected individual PNGS mutants. 25751231 3 18 theme PNGS 623:626 arg1 role 609:612 the functional role 594:612 the functional role of these PNGS 594:626 To further understand the functional role of these PNGS, we generated double and multiple mutants from selected individual PNGS mutants. 25751231 8 19 theme mutation 1802:1809 arg1 background 1782:1791 the genetic background 1770:1791 the genetic background of N197D mutation of gp120, which should provide valuable information for a better understanding of the interplay between HIV-1 and VRC01/03 1770:1932 CONCLUSIONS: The data indicate that N463 plays an important role in regulating the CD4bs MAbs VRC01/VRC03 sensitivity in the genetic background of N197D mutation of gp120, which should provide valuable information for a better understanding of the interplay between HIV-1 and VRC01/03. 25751231 2 20 from effects 496:502 arg1 infectivity 507:517 infectivity 507:517 infectivity 507:517 METHODS: In our previous work, 25 potential N-linked glycosylation sites (PNGS) of a CRF07_BC isolate of HIV-1 were individually mutated, and the resulting effects on infectivity and antibody-mediated neutralization were evaluated. 25751231 2 20 from effects 496:502 arg1 neutralization 541:554 antibody-mediated neutralization 523:554 antibody-mediated neutralization 523:554 METHODS: In our previous work, 25 potential N-linked glycosylation sites (PNGS) of a CRF07_BC isolate of HIV-1 were individually mutated, and the resulting effects on infectivity and antibody-mediated neutralization were evaluated. 25751231 0 21 theme Mutant 40:45 arg1 gp120 47:51 a Mutant gp120 38:51 a Mutant gp120 38:51 N463 Glycosylation Site on V5 Loop of a Mutant gp120 Regulates the Sensitivity of HIV-1 to Neutralizing Monoclonal Antibodies VRC01/03. 25751231 4 22 from donors 905:910 arg1 antibodies 845:854 monoclonal antibodies 834:854 monoclonal antibodies (nMAbs) 834:862 The effects were then evaluated by examining infectivity and sensitivity to antibody-mediated neutralization by neutralizing monoclonal antibodies (nMAbs) and serum antibodies from HIV-1 positive donors. 25751231 4 22 from donors 905:910 arg1 antibodies 874:883 serum antibodies 868:883 serum antibodies from HIV-1 positive donors 868:910 The effects were then evaluated by examining infectivity and sensitivity to antibody-mediated neutralization by neutralizing monoclonal antibodies (nMAbs) and serum antibodies from HIV-1 positive donors. 25751231 4 22 from donors 905:910 arg1 nMAbs 857:861 nMAbs 857:861 nMAbs 857:861 The effects were then evaluated by examining infectivity and sensitivity to antibody-mediated neutralization by neutralizing monoclonal antibodies (nMAbs) and serum antibodies from HIV-1 positive donors. 25751231 8 23 theme gp120 1814:1818 arg1 mutation 1802:1809 N197D mutation 1796:1809 N197D mutation 1796:1809 CONCLUSIONS: The data indicate that N463 plays an important role in regulating the CD4bs MAbs VRC01/VRC03 sensitivity in the genetic background of N197D mutation of gp120, which should provide valuable information for a better understanding of the interplay between HIV-1 and VRC01/03. 25751231 0 24 dep Antibodies 115:124 arg1 VRC01/03 126:133 VRC01/03 126:133 VRC01/03 126:133 N463 Glycosylation Site on V5 Loop of a Mutant gp120 Regulates the Sensitivity of HIV-1 to Neutralizing Monoclonal Antibodies VRC01/03. 25751231 0 25 from Site 19:22 arg1 Loop 30:33 V5 Loop 27:33 V5 Loop of a Mutant gp120 27:51 N463 Glycosylation Site on V5 Loop of a Mutant gp120 Regulates the Sensitivity of HIV-1 to Neutralizing Monoclonal Antibodies VRC01/03. 25751231 1 26 theme HIV-1 148:152 arg1 gp120/gp41 154:163 HIV-1 gp120/gp41 148:163 HIV-1 gp120/gp41 148:163 BACKGROUND: HIV-1 gp120/gp41 is heavily modified by n-linked carbohydrates that play important roles either in correct folding or in shielding vulnerable viral protein surfaces from antibody recognition. 25751231 2 27 gly glycosylation 393:405 arg2 PNGS 414:417 PNGS 414:417 PNGS 414:417 METHODS: In our previous work, 25 potential N-linked glycosylation sites (PNGS) of a CRF07_BC isolate of HIV-1 were individually mutated, and the resulting effects on infectivity and antibody-mediated neutralization were evaluated. 25751231 2 27 gly glycosylation 393:405 arg2 sites 407:411 25 potential N-linked glycosylation sites 371:411 25 potential N-linked glycosylation sites (PNGS) of a CRF07_BC isolate of HIV-1 371:449 METHODS: In our previous work, 25 potential N-linked glycosylation sites (PNGS) of a CRF07_BC isolate of HIV-1 were individually mutated, and the resulting effects on infectivity and antibody-mediated neutralization were evaluated. 25751231 2 27 gly glycosylation 393:405 arg2 25 371:372 25 371:372 25 371:372 METHODS: In our previous work, 25 potential N-linked glycosylation sites (PNGS) of a CRF07_BC isolate of HIV-1 were individually mutated, and the resulting effects on infectivity and antibody-mediated neutralization were evaluated. 25751231 2 27 gly glycosylation 393:405 arg1 isolate 434:440 a CRF07_BC isolate 423:440 a CRF07_BC isolate of HIV-1 423:449 METHODS: In our previous work, 25 potential N-linked glycosylation sites (PNGS) of a CRF07_BC isolate of HIV-1 were individually mutated, and the resulting effects on infectivity and antibody-mediated neutralization were evaluated. 25751231 2 27 gly glycosylation 393:405 arg2 isolate 434:440 a CRF07_BC isolate 423:440 a CRF07_BC isolate of HIV-1 423:449 METHODS: In our previous work, 25 potential N-linked glycosylation sites (PNGS) of a CRF07_BC isolate of HIV-1 were individually mutated, and the resulting effects on infectivity and antibody-mediated neutralization were evaluated. 25751231 6 28 theme strong 1355:1360 arg1 effect 1374:1379 a strong synergistic effect 1353:1379 a strong synergistic effect 1353:1379 In terms of neutralization sensitivity to known nMAbs, we found that adding N463Q mutation to all the gp120 mutants containing N197D significantly increased neutralization sensitivity to VRC01 and VRC03, suggesting N197 and N463 have a strong synergistic effect in regulating the neutralizing sensitivity of HIV-1 to the anti-CD4bs nMAbs VRC01/VRC03. 25751231 2 29 theme resulting 486:494 arg1 effects 496:502 the resulting effects 482:502 the resulting effects on infectivity and antibody-mediated neutralization 482:554 METHODS: In our previous work, 25 potential N-linked glycosylation sites (PNGS) of a CRF07_BC isolate of HIV-1 were individually mutated, and the resulting effects on infectivity and antibody-mediated neutralization were evaluated. 25751231 2 30 theme N-linked 384:391 arg1 sites 407:411 25 potential N-linked glycosylation sites 371:411 25 potential N-linked glycosylation sites (PNGS) of a CRF07_BC isolate of HIV-1 371:449 METHODS: In our previous work, 25 potential N-linked glycosylation sites (PNGS) of a CRF07_BC isolate of HIV-1 were individually mutated, and the resulting effects on infectivity and antibody-mediated neutralization were evaluated. 25751231 2 30 theme N-linked 384:391 arg1 isolate 434:440 a CRF07_BC isolate 423:440 a CRF07_BC isolate of HIV-1 423:449 METHODS: In our previous work, 25 potential N-linked glycosylation sites (PNGS) of a CRF07_BC isolate of HIV-1 were individually mutated, and the resulting effects on infectivity and antibody-mediated neutralization were evaluated. 25751231 2 30 theme N-linked 384:391 arg1 PNGS 414:417 PNGS 414:417 PNGS 414:417 METHODS: In our previous work, 25 potential N-linked glycosylation sites (PNGS) of a CRF07_BC isolate of HIV-1 were individually mutated, and the resulting effects on infectivity and antibody-mediated neutralization were evaluated. 25751231 0 31 theme HIV-1 82:86 arg1 Sensitivity 67:77 the Sensitivity 63:77 the Sensitivity of HIV-1 to Neutralizing Monoclonal Antibodies VRC01/03 63:133 N463 Glycosylation Site on V5 Loop of a Mutant gp120 Regulates the Sensitivity of HIV-1 to Neutralizing Monoclonal Antibodies VRC01/03. 25751231 5 32 theme viral 1100:1104 arg1 infectivity 1106:1116 reduced viral infectivity 1092:1116 reduced viral infectivity 1092:1116 RESULTS: Infectivity results showed that, among the 12 combined PNGS mutants, only 197M.1 (N197D/N301Q) lost infectivity completely, whereas all others (except for 197M.6) showed reduced viral infectivity. 25751231 2 33 theme CRF07_BC 425:432 arg1 isolate 434:440 a CRF07_BC isolate 423:440 a CRF07_BC isolate of HIV-1 423:449 METHODS: In our previous work, 25 potential N-linked glycosylation sites (PNGS) of a CRF07_BC isolate of HIV-1 were individually mutated, and the resulting effects on infectivity and antibody-mediated neutralization were evaluated. 25751231 0 34 theme N463 0:3 arg1 Site 19:22 N463 Glycosylation Site 0:22 N463 Glycosylation Site on V5 Loop of a Mutant gp120 0:51 N463 Glycosylation Site on V5 Loop of a Mutant gp120 Regulates the Sensitivity of HIV-1 to Neutralizing Monoclonal Antibodies VRC01/03. 25751231 1 35 theme vulnerable 279:288 arg1 surfaces 304:311 shielding vulnerable viral protein surfaces 269:311 shielding vulnerable viral protein surfaces from antibody recognition 269:337 BACKGROUND: HIV-1 gp120/gp41 is heavily modified by n-linked carbohydrates that play important roles either in correct folding or in shielding vulnerable viral protein surfaces from antibody recognition. 25751231 5 36 theme combined 968:975 arg1 mutants 982:988 the 12 combined PNGS mutants 961:988 the 12 combined PNGS mutants 961:988 RESULTS: Infectivity results showed that, among the 12 combined PNGS mutants, only 197M.1 (N197D/N301Q) lost infectivity completely, whereas all others (except for 197M.6) showed reduced viral infectivity. 25751231 3 37 theme double 642:647 arg1 mutants 662:668 double and multiple mutants 642:668 double and multiple mutants from selected individual PNGS mutants 642:706 To further understand the functional role of these PNGS, we generated double and multiple mutants from selected individual PNGS mutants. 25751231 0 38 theme V5 27:28 arg1 Loop 30:33 V5 Loop 27:33 V5 Loop of a Mutant gp120 27:51 N463 Glycosylation Site on V5 Loop of a Mutant gp120 Regulates the Sensitivity of HIV-1 to Neutralizing Monoclonal Antibodies VRC01/03. 25751231 1 39 theme protein 296:302 arg1 surfaces 304:311 shielding vulnerable viral protein surfaces 269:311 shielding vulnerable viral protein surfaces from antibody recognition 269:337 BACKGROUND: HIV-1 gp120/gp41 is heavily modified by n-linked carbohydrates that play important roles either in correct folding or in shielding vulnerable viral protein surfaces from antibody recognition. 25751231 6 40 theme neutralizing 1399:1410 arg1 sensitivity 1412:1422 the neutralizing sensitivity 1395:1422 the neutralizing sensitivity of HIV-1 to the anti-CD4bs nMAbs VRC01/VRC03 1395:1467 In terms of neutralization sensitivity to known nMAbs, we found that adding N463Q mutation to all the gp120 mutants containing N197D significantly increased neutralization sensitivity to VRC01 and VRC03, suggesting N197 and N463 have a strong synergistic effect in regulating the neutralizing sensitivity of HIV-1 to the anti-CD4bs nMAbs VRC01/VRC03. 25751231 7 41 theme gp120 1527:1531 arg1 structures 1513:1522 the available structures 1499:1522 the available structures of gp120 alone and in complex with CD4 and various nMAbs 1499:1579 Structural analysis based on the available structures of gp120 alone and in complex with CD4 and various nMAbs elucidates a molecular rationale for this experimental observation. 25751231 3 42 theme multiple 653:660 arg1 mutants 662:668 double and multiple mutants 642:668 double and multiple mutants from selected individual PNGS mutants 642:706 To further understand the functional role of these PNGS, we generated double and multiple mutants from selected individual PNGS mutants. 25751231 3 43 theme individual 684:693 arg1 mutants 700:706 selected individual PNGS mutants 675:706 selected individual PNGS mutants 675:706 To further understand the functional role of these PNGS, we generated double and multiple mutants from selected individual PNGS mutants. 25751231 6 44 theme neutralization 1276:1289 arg1 sensitivity 1291:1301 neutralization sensitivity 1276:1301 neutralization sensitivity to VRC01 and VRC03 1276:1320 In terms of neutralization sensitivity to known nMAbs, we found that adding N463Q mutation to all the gp120 mutants containing N197D significantly increased neutralization sensitivity to VRC01 and VRC03, suggesting N197 and N463 have a strong synergistic effect in regulating the neutralizing sensitivity of HIV-1 to the anti-CD4bs nMAbs VRC01/VRC03. 25751231 8 45 theme important 1699:1707 arg1 role 1709:1712 an important role 1696:1712 an important role 1696:1712 CONCLUSIONS: The data indicate that N463 plays an important role in regulating the CD4bs MAbs VRC01/VRC03 sensitivity in the genetic background of N197D mutation of gp120, which should provide valuable information for a better understanding of the interplay between HIV-1 and VRC01/03. 25751231 7 46 theme Structural 1470:1479 arg1 analysis 1481:1488 Structural analysis 1470:1488 Structural analysis based on the available structures of gp120 alone and in complex with CD4 and various nMAbs 1470:1579 Structural analysis based on the available structures of gp120 alone and in complex with CD4 and various nMAbs elucidates a molecular rationale for this experimental observation. 25751231 4 47 theme positive 896:903 arg1 donors 905:910 HIV-1 positive donors 890:910 HIV-1 positive donors 890:910 The effects were then evaluated by examining infectivity and sensitivity to antibody-mediated neutralization by neutralizing monoclonal antibodies (nMAbs) and serum antibodies from HIV-1 positive donors. 25751231 6 48 contain have 1348:1351 arg1 N197 1334:1337 N197 1334:1337 N197 1334:1337 In terms of neutralization sensitivity to known nMAbs, we found that adding N463Q mutation to all the gp120 mutants containing N197D significantly increased neutralization sensitivity to VRC01 and VRC03, suggesting N197 and N463 have a strong synergistic effect in regulating the neutralizing sensitivity of HIV-1 to the anti-CD4bs nMAbs VRC01/VRC03. 25751231 6 48 contain have 1348:1351 arg2 effect 1374:1379 a strong synergistic effect 1353:1379 a strong synergistic effect 1353:1379 In terms of neutralization sensitivity to known nMAbs, we found that adding N463Q mutation to all the gp120 mutants containing N197D significantly increased neutralization sensitivity to VRC01 and VRC03, suggesting N197 and N463 have a strong synergistic effect in regulating the neutralizing sensitivity of HIV-1 to the anti-CD4bs nMAbs VRC01/VRC03. 25751231 6 48 contain have 1348:1351 arg1 N463 1343:1346 N463 1343:1346 N463 1343:1346 In terms of neutralization sensitivity to known nMAbs, we found that adding N463Q mutation to all the gp120 mutants containing N197D significantly increased neutralization sensitivity to VRC01 and VRC03, suggesting N197 and N463 have a strong synergistic effect in regulating the neutralizing sensitivity of HIV-1 to the anti-CD4bs nMAbs VRC01/VRC03. 25751231 4 49 theme serum 868:872 arg1 antibodies 874:883 serum antibodies 868:883 serum antibodies from HIV-1 positive donors 868:910 The effects were then evaluated by examining infectivity and sensitivity to antibody-mediated neutralization by neutralizing monoclonal antibodies (nMAbs) and serum antibodies from HIV-1 positive donors. 25751231 0 50 theme Monoclonal 104:113 arg1 Antibodies 115:124 Neutralizing Monoclonal Antibodies VRC01/03 91:133 Neutralizing Monoclonal Antibodies VRC01/03 91:133 N463 Glycosylation Site on V5 Loop of a Mutant gp120 Regulates the Sensitivity of HIV-1 to Neutralizing Monoclonal Antibodies VRC01/03. 25751231 8 51 theme MAbs 1738:1741 arg1 sensitivity 1755:1765 the CD4bs MAbs VRC01/VRC03 sensitivity 1728:1765 the CD4bs MAbs VRC01/VRC03 sensitivity 1728:1765 CONCLUSIONS: The data indicate that N463 plays an important role in regulating the CD4bs MAbs VRC01/VRC03 sensitivity in the genetic background of N197D mutation of gp120, which should provide valuable information for a better understanding of the interplay between HIV-1 and VRC01/03. 25751231 2 52 theme antibody-mediated 523:539 arg1 neutralization 541:554 antibody-mediated neutralization 523:554 antibody-mediated neutralization 523:554 METHODS: In our previous work, 25 potential N-linked glycosylation sites (PNGS) of a CRF07_BC isolate of HIV-1 were individually mutated, and the resulting effects on infectivity and antibody-mediated neutralization were evaluated. 25751231 6 53 theme neutralization 1131:1144 arg1 sensitivity 1146:1156 neutralization sensitivity 1131:1156 neutralization sensitivity to known nMAbs 1131:1171 In terms of neutralization sensitivity to known nMAbs, we found that adding N463Q mutation to all the gp120 mutants containing N197D significantly increased neutralization sensitivity to VRC01 and VRC03, suggesting N197 and N463 have a strong synergistic effect in regulating the neutralizing sensitivity of HIV-1 to the anti-CD4bs nMAbs VRC01/VRC03. 25751231 7 54 theme experimental 1623:1634 arg1 observation 1636:1646 this experimental observation 1618:1646 this experimental observation 1618:1646 Structural analysis based on the available structures of gp120 alone and in complex with CD4 and various nMAbs elucidates a molecular rationale for this experimental observation. 25751231 7 55 theme molecular 1594:1602 arg1 rationale 1604:1612 a molecular rationale 1592:1612 a molecular rationale for this experimental observation 1592:1646 Structural analysis based on the available structures of gp120 alone and in complex with CD4 and various nMAbs elucidates a molecular rationale for this experimental observation. 25751231 6 56 theme N463Q 1195:1199 arg1 mutation 1201:1208 N463Q mutation 1195:1208 N463Q mutation 1195:1208 In terms of neutralization sensitivity to known nMAbs, we found that adding N463Q mutation to all the gp120 mutants containing N197D significantly increased neutralization sensitivity to VRC01 and VRC03, suggesting N197 and N463 have a strong synergistic effect in regulating the neutralizing sensitivity of HIV-1 to the anti-CD4bs nMAbs VRC01/VRC03. 25751231 0 57 theme gp120 47:51 arg1 Loop 30:33 V5 Loop 27:33 V5 Loop of a Mutant gp120 27:51 N463 Glycosylation Site on V5 Loop of a Mutant gp120 Regulates the Sensitivity of HIV-1 to Neutralizing Monoclonal Antibodies VRC01/03. 25751231 8 58 theme N197D 1796:1800 arg1 mutation 1802:1809 N197D mutation 1796:1809 N197D mutation 1796:1809 CONCLUSIONS: The data indicate that N463 plays an important role in regulating the CD4bs MAbs VRC01/VRC03 sensitivity in the genetic background of N197D mutation of gp120, which should provide valuable information for a better understanding of the interplay between HIV-1 and VRC01/03. 25751231 7 59 theme various 1567:1573 arg1 nMAbs 1575:1579 various nMAbs 1567:1579 various nMAbs 1567:1579 Structural analysis based on the available structures of gp120 alone and in complex with CD4 and various nMAbs elucidates a molecular rationale for this experimental observation. 25751231 6 60 theme synergistic 1362:1372 arg1 effect 1374:1379 a strong synergistic effect 1353:1379 a strong synergistic effect 1353:1379 In terms of neutralization sensitivity to known nMAbs, we found that adding N463Q mutation to all the gp120 mutants containing N197D significantly increased neutralization sensitivity to VRC01 and VRC03, suggesting N197 and N463 have a strong synergistic effect in regulating the neutralizing sensitivity of HIV-1 to the anti-CD4bs nMAbs VRC01/VRC03. 25751231 5 61 theme PNGS 977:980 arg1 mutants 982:988 the 12 combined PNGS mutants 961:988 the 12 combined PNGS mutants 961:988 RESULTS: Infectivity results showed that, among the 12 combined PNGS mutants, only 197M.1 (N197D/N301Q) lost infectivity completely, whereas all others (except for 197M.6) showed reduced viral infectivity. 25751231 1 62 link n-linked 188:195 arg1 carbohydrates 197:209 n-linked carbohydrates 188:209 n-linked carbohydrates that play important roles either in correct folding or in shielding vulnerable viral protein surfaces from antibody recognition 188:337 BACKGROUND: HIV-1 gp120/gp41 is heavily modified by n-linked carbohydrates that play important roles either in correct folding or in shielding vulnerable viral protein surfaces from antibody recognition. 25751231 5 63 theme reduced 1092:1098 arg1 infectivity 1106:1116 reduced viral infectivity 1092:1116 reduced viral infectivity 1092:1116 RESULTS: Infectivity results showed that, among the 12 combined PNGS mutants, only 197M.1 (N197D/N301Q) lost infectivity completely, whereas all others (except for 197M.6) showed reduced viral infectivity. 25751231 2 64 theme potential 374:382 arg1 sites 407:411 25 potential N-linked glycosylation sites 371:411 25 potential N-linked glycosylation sites (PNGS) of a CRF07_BC isolate of HIV-1 371:449 METHODS: In our previous work, 25 potential N-linked glycosylation sites (PNGS) of a CRF07_BC isolate of HIV-1 were individually mutated, and the resulting effects on infectivity and antibody-mediated neutralization were evaluated. 25751231 2 64 theme potential 374:382 arg1 isolate 434:440 a CRF07_BC isolate 423:440 a CRF07_BC isolate of HIV-1 423:449 METHODS: In our previous work, 25 potential N-linked glycosylation sites (PNGS) of a CRF07_BC isolate of HIV-1 were individually mutated, and the resulting effects on infectivity and antibody-mediated neutralization were evaluated. 25751231 2 64 theme potential 374:382 arg1 PNGS 414:417 PNGS 414:417 PNGS 414:417 METHODS: In our previous work, 25 potential N-linked glycosylation sites (PNGS) of a CRF07_BC isolate of HIV-1 were individually mutated, and the resulting effects on infectivity and antibody-mediated neutralization were evaluated. 25751231 0 65 theme Glycosylation 5:17 arg1 Site 19:22 N463 Glycosylation Site 0:22 N463 Glycosylation Site on V5 Loop of a Mutant gp120 0:51 N463 Glycosylation Site on V5 Loop of a Mutant gp120 Regulates the Sensitivity of HIV-1 to Neutralizing Monoclonal Antibodies VRC01/03. 25751231 8 66 theme valuable 1842:1849 arg1 information 1851:1861 valuable information 1842:1861 valuable information for a better understanding of the interplay between HIV-1 and VRC01/03 1842:1932 CONCLUSIONS: The data indicate that N463 plays an important role in regulating the CD4bs MAbs VRC01/VRC03 sensitivity in the genetic background of N197D mutation of gp120, which should provide valuable information for a better understanding of the interplay between HIV-1 and VRC01/03. 25751231 5 67 theme Infectivity 922:932 arg1 results 934:940 Infectivity results 922:940 Infectivity results 922:940 RESULTS: Infectivity results showed that, among the 12 combined PNGS mutants, only 197M.1 (N197D/N301Q) lost infectivity completely, whereas all others (except for 197M.6) showed reduced viral infectivity. 25751231 1 68 theme shielding 269:277 arg1 surfaces 304:311 shielding vulnerable viral protein surfaces 269:311 shielding vulnerable viral protein surfaces from antibody recognition 269:337 BACKGROUND: HIV-1 gp120/gp41 is heavily modified by n-linked carbohydrates that play important roles either in correct folding or in shielding vulnerable viral protein surfaces from antibody recognition. 25751231 6 69 contain containing 1235:1244 arg1 mutants 1227:1233 all the gp120 mutants 1213:1233 all the gp120 mutants containing N197D 1213:1250 In terms of neutralization sensitivity to known nMAbs, we found that adding N463Q mutation to all the gp120 mutants containing N197D significantly increased neutralization sensitivity to VRC01 and VRC03, suggesting N197 and N463 have a strong synergistic effect in regulating the neutralizing sensitivity of HIV-1 to the anti-CD4bs nMAbs VRC01/VRC03. 25751231 6 69 contain containing 1235:1244 arg2 N197D 1246:1250 N197D 1246:1250 N197D 1246:1250 In terms of neutralization sensitivity to known nMAbs, we found that adding N463Q mutation to all the gp120 mutants containing N197D significantly increased neutralization sensitivity to VRC01 and VRC03, suggesting N197 and N463 have a strong synergistic effect in regulating the neutralizing sensitivity of HIV-1 to the anti-CD4bs nMAbs VRC01/VRC03. 25751231 6 70 theme HIV-1 1427:1431 arg1 sensitivity 1412:1422 the neutralizing sensitivity 1395:1422 the neutralizing sensitivity of HIV-1 to the anti-CD4bs nMAbs VRC01/VRC03 1395:1467 In terms of neutralization sensitivity to known nMAbs, we found that adding N463Q mutation to all the gp120 mutants containing N197D significantly increased neutralization sensitivity to VRC01 and VRC03, suggesting N197 and N463 have a strong synergistic effect in regulating the neutralizing sensitivity of HIV-1 to the anti-CD4bs nMAbs VRC01/VRC03. 25751231 1 71 theme viral 290:294 arg1 surfaces 304:311 shielding vulnerable viral protein surfaces 269:311 shielding vulnerable viral protein surfaces from antibody recognition 269:337 BACKGROUND: HIV-1 gp120/gp41 is heavily modified by n-linked carbohydrates that play important roles either in correct folding or in shielding vulnerable viral protein surfaces from antibody recognition. 25751231 2 72 theme HIV-1 445:449 arg1 isolate 434:440 a CRF07_BC isolate 423:440 a CRF07_BC isolate of HIV-1 423:449 METHODS: In our previous work, 25 potential N-linked glycosylation sites (PNGS) of a CRF07_BC isolate of HIV-1 were individually mutated, and the resulting effects on infectivity and antibody-mediated neutralization were evaluated. 25751231 2 73 link N-linked 384:391 arg1 sites 407:411 25 potential N-linked glycosylation sites 371:411 25 potential N-linked glycosylation sites (PNGS) of a CRF07_BC isolate of HIV-1 371:449 METHODS: In our previous work, 25 potential N-linked glycosylation sites (PNGS) of a CRF07_BC isolate of HIV-1 were individually mutated, and the resulting effects on infectivity and antibody-mediated neutralization were evaluated. 25751231 2 73 link N-linked 384:391 arg1 isolate 434:440 a CRF07_BC isolate 423:440 a CRF07_BC isolate of HIV-1 423:449 METHODS: In our previous work, 25 potential N-linked glycosylation sites (PNGS) of a CRF07_BC isolate of HIV-1 were individually mutated, and the resulting effects on infectivity and antibody-mediated neutralization were evaluated. 25751231 2 73 link N-linked 384:391 arg1 PNGS 414:417 PNGS 414:417 PNGS 414:417 METHODS: In our previous work, 25 potential N-linked glycosylation sites (PNGS) of a CRF07_BC isolate of HIV-1 were individually mutated, and the resulting effects on infectivity and antibody-mediated neutralization were evaluated. 25751231 4 74 theme monoclonal 834:843 arg1 antibodies 845:854 monoclonal antibodies 834:854 monoclonal antibodies (nMAbs) 834:862 The effects were then evaluated by examining infectivity and sensitivity to antibody-mediated neutralization by neutralizing monoclonal antibodies (nMAbs) and serum antibodies from HIV-1 positive donors. 25751231 4 74 theme monoclonal 834:843 arg1 nMAbs 857:861 nMAbs 857:861 nMAbs 857:861 The effects were then evaluated by examining infectivity and sensitivity to antibody-mediated neutralization by neutralizing monoclonal antibodies (nMAbs) and serum antibodies from HIV-1 positive donors. 25751231 2 75 theme glycosylation 393:405 arg1 sites 407:411 25 potential N-linked glycosylation sites 371:411 25 potential N-linked glycosylation sites (PNGS) of a CRF07_BC isolate of HIV-1 371:449 METHODS: In our previous work, 25 potential N-linked glycosylation sites (PNGS) of a CRF07_BC isolate of HIV-1 were individually mutated, and the resulting effects on infectivity and antibody-mediated neutralization were evaluated. 25751231 2 75 theme glycosylation 393:405 arg1 isolate 434:440 a CRF07_BC isolate 423:440 a CRF07_BC isolate of HIV-1 423:449 METHODS: In our previous work, 25 potential N-linked glycosylation sites (PNGS) of a CRF07_BC isolate of HIV-1 were individually mutated, and the resulting effects on infectivity and antibody-mediated neutralization were evaluated. 25751231 2 75 theme glycosylation 393:405 arg1 PNGS 414:417 PNGS 414:417 PNGS 414:417 METHODS: In our previous work, 25 potential N-linked glycosylation sites (PNGS) of a CRF07_BC isolate of HIV-1 were individually mutated, and the resulting effects on infectivity and antibody-mediated neutralization were evaluated. 25751231 1 76 from recognition 327:337 arg1 surfaces 304:311 shielding vulnerable viral protein surfaces 269:311 shielding vulnerable viral protein surfaces from antibody recognition 269:337 BACKGROUND: HIV-1 gp120/gp41 is heavily modified by n-linked carbohydrates that play important roles either in correct folding or in shielding vulnerable viral protein surfaces from antibody recognition. 25751231 1 77 mod modified 176:183 arg1 gp120/gp41 154:163 HIV-1 gp120/gp41 148:163 HIV-1 gp120/gp41 148:163 BACKGROUND: HIV-1 gp120/gp41 is heavily modified by n-linked carbohydrates that play important roles either in correct folding or in shielding vulnerable viral protein surfaces from antibody recognition. 25751231 1 77 mod modified 176:183 arg3 carbohydrates 197:209 n-linked carbohydrates 188:209 n-linked carbohydrates that play important roles either in correct folding or in shielding vulnerable viral protein surfaces from antibody recognition 188:337 BACKGROUND: HIV-1 gp120/gp41 is heavily modified by n-linked carbohydrates that play important roles either in correct folding or in shielding vulnerable viral protein surfaces from antibody recognition. 25751231 2 78 theme isolate 434:440 arg1 sites 407:411 25 potential N-linked glycosylation sites 371:411 25 potential N-linked glycosylation sites (PNGS) of a CRF07_BC isolate of HIV-1 371:449 METHODS: In our previous work, 25 potential N-linked glycosylation sites (PNGS) of a CRF07_BC isolate of HIV-1 were individually mutated, and the resulting effects on infectivity and antibody-mediated neutralization were evaluated. 25751231 2 78 theme isolate 434:440 arg1 isolate 434:440 a CRF07_BC isolate 423:440 a CRF07_BC isolate of HIV-1 423:449 METHODS: In our previous work, 25 potential N-linked glycosylation sites (PNGS) of a CRF07_BC isolate of HIV-1 were individually mutated, and the resulting effects on infectivity and antibody-mediated neutralization were evaluated. 25751231 2 78 theme isolate 434:440 arg1 PNGS 414:417 PNGS 414:417 PNGS 414:417 METHODS: In our previous work, 25 potential N-linked glycosylation sites (PNGS) of a CRF07_BC isolate of HIV-1 were individually mutated, and the resulting effects on infectivity and antibody-mediated neutralization were evaluated. 25751231 1 79 theme antibody 318:325 arg1 recognition 327:337 antibody recognition 318:337 antibody recognition 318:337 BACKGROUND: HIV-1 gp120/gp41 is heavily modified by n-linked carbohydrates that play important roles either in correct folding or in shielding vulnerable viral protein surfaces from antibody recognition. 25751231 5 80 dep 197M.6 1077:1082 arg1 except 1066:1071 except 1066:1071 except 1066:1071 RESULTS: Infectivity results showed that, among the 12 combined PNGS mutants, only 197M.1 (N197D/N301Q) lost infectivity completely, whereas all others (except for 197M.6) showed reduced viral infectivity. 25751231 4 81 theme antibody-mediated 785:801 arg1 neutralization 803:816 antibody-mediated neutralization 785:816 antibody-mediated neutralization 785:816 The effects were then evaluated by examining infectivity and sensitivity to antibody-mediated neutralization by neutralizing monoclonal antibodies (nMAbs) and serum antibodies from HIV-1 positive donors. 25751231 2 82 theme previous 356:363 arg1 work 365:368 our previous work 352:368 our previous work 352:368 METHODS: In our previous work, 25 potential N-linked glycosylation sites (PNGS) of a CRF07_BC isolate of HIV-1 were individually mutated, and the resulting effects on infectivity and antibody-mediated neutralization were evaluated. 25751231 1 83 theme important 221:229 arg1 roles 231:235 important roles 221:235 important roles 221:235 BACKGROUND: HIV-1 gp120/gp41 is heavily modified by n-linked carbohydrates that play important roles either in correct folding or in shielding vulnerable viral protein surfaces from antibody recognition. 25751231 3 84 theme PNGS 695:698 arg1 mutants 700:706 selected individual PNGS mutants 675:706 selected individual PNGS mutants 675:706 To further understand the functional role of these PNGS, we generated double and multiple mutants from selected individual PNGS mutants. 25751231 6 85 theme nMAbs 1451:1455 arg1 VRC01/VRC03 1457:1467 the anti-CD4bs nMAbs VRC01/VRC03 1436:1467 the anti-CD4bs nMAbs VRC01/VRC03 1436:1467 In terms of neutralization sensitivity to known nMAbs, we found that adding N463Q mutation to all the gp120 mutants containing N197D significantly increased neutralization sensitivity to VRC01 and VRC03, suggesting N197 and N463 have a strong synergistic effect in regulating the neutralizing sensitivity of HIV-1 to the anti-CD4bs nMAbs VRC01/VRC03. 25336660 6 0 dep sites 974:978 arg1 Asn-67 981:986 Asn-67 981:986 Asn-67 981:986 Site-directed mutagenesis confirmed four N-glycosylazhytion sites (Asn-67, Asn-91, Asn-436, and Asn-612) in human ADAM8. 25336660 6 0 dep sites 974:978 arg1 sites 974:978 four N-glycosylazhytion sites 950:978 four N-glycosylazhytion sites (Asn-67, Asn-91, Asn-436, and Asn-612) 950:1017 Site-directed mutagenesis confirmed four N-glycosylazhytion sites (Asn-67, Asn-91, Asn-436, and Asn-612) in human ADAM8. 25336660 6 0 dep sites 974:978 arg1 Asn-436 997:1003 Asn-436 997:1003 Asn-436 997:1003 Site-directed mutagenesis confirmed four N-glycosylazhytion sites (Asn-67, Asn-91, Asn-436, and Asn-612) in human ADAM8. 25336660 6 0 dep sites 974:978 arg1 Asn-612 1010:1016 Asn-612 1010:1016 Asn-612 1010:1016 Site-directed mutagenesis confirmed four N-glycosylazhytion sites (Asn-67, Asn-91, Asn-436, and Asn-612) in human ADAM8. 25336660 6 0 dep sites 974:978 arg1 Asn-91 989:994 Asn-91 989:994 Asn-91 989:994 Site-directed mutagenesis confirmed four N-glycosylazhytion sites (Asn-67, Asn-91, Asn-436, and Asn-612) in human ADAM8. 25336660 7 1 theme high 1083:1086 arg1 mannose 1088:1094 high mannose 1083:1094 high mannose 1083:1094 The Asn-67 and Asn-91 prodomain sites contained high mannose, whereas complex type N-glycosylation was observed on Asn-436 and Asn-612 in the active and remnant forms. 25336660 1 2 theme human 158:162 arg1 tumors 171:176 human breast tumors 158:176 human breast tumors 158:176 The transmembrane ADAM8 (A Disintegrin And Metalloproteinase 8) protein is abundantly expressed in human breast tumors and derived metastases compared with normal breast tissue, and plays critical roles in aggressive Triple-Negative breast cancers (TNBCs). 25336660 1 3 theme critical 247:254 arg1 roles 256:260 critical roles 247:260 critical roles 247:260 The transmembrane ADAM8 (A Disintegrin And Metalloproteinase 8) protein is abundantly expressed in human breast tumors and derived metastases compared with normal breast tissue, and plays critical roles in aggressive Triple-Negative breast cancers (TNBCs). 25336660 7 4 theme active 1177:1182 arg1 forms 1196:1200 the active and remnant forms 1173:1200 the active and remnant forms 1173:1200 The Asn-67 and Asn-91 prodomain sites contained high mannose, whereas complex type N-glycosylation was observed on Asn-436 and Asn-612 in the active and remnant forms. 25336660 5 5 theme breast 864:869 arg1 cells 878:882 ERα-negative breast cancer cells 851:882 ERα-negative breast cancer cells 851:882 Consistently ADAM8 dimers were detected on the surface of ERα-negative breast cancer cells but not on ERα-positive ones. 25336660 1 6 theme breast 164:169 arg1 tumors 171:176 human breast tumors 158:176 human breast tumors 158:176 The transmembrane ADAM8 (A Disintegrin And Metalloproteinase 8) protein is abundantly expressed in human breast tumors and derived metastases compared with normal breast tissue, and plays critical roles in aggressive Triple-Negative breast cancers (TNBCs). 25336660 8 7 from exit 1323:1326 arg1 essential 1237:1245 essential 1237:1245 essential 1237:1245 The Asn-91 and Asn-612 sites were essential for its correct processing and cell surface localization, in particular its exit from the Golgi and endoplasmic reticulum, respectively. 25336660 8 7 from exit 1323:1326 arg1 sites 1226:1230 The Asn-91 and Asn-612 sites 1203:1230 sites 1226:1230 The Asn-91 and Asn-612 sites were essential for its correct processing and cell surface localization, in particular its exit from the Golgi and endoplasmic reticulum, respectively. 25336660 10 8 theme modest 1525:1530 arg1 effects 1532:1538 only modest effects 1520:1538 only modest effects 1520:1538 In contrast, mutation of the Asn-67 site had only modest effects on enzyme stability and processing. 25336660 7 9 located observed 1138:1145 arg1 Asn-612 1162:1168 Asn-612 1162:1168 Asn-612 1162:1168 The Asn-67 and Asn-91 prodomain sites contained high mannose, whereas complex type N-glycosylation was observed on Asn-436 and Asn-612 in the active and remnant forms. 25336660 7 9 located observed 1138:1145 arg1 Asn-436 1150:1156 Asn-436 1150:1156 Asn-436 1150:1156 The Asn-67 and Asn-91 prodomain sites contained high mannose, whereas complex type N-glycosylation was observed on Asn-436 and Asn-612 in the active and remnant forms. 25336660 7 9 located observed 1138:1145 arg1 forms 1196:1200 the active and remnant forms 1173:1200 the active and remnant forms 1173:1200 The Asn-67 and Asn-91 prodomain sites contained high mannose, whereas complex type N-glycosylation was observed on Asn-436 and Asn-612 in the active and remnant forms. 25336660 7 9 located observed 1138:1145 arg2 N-glycosylation 1118:1132 complex type N-glycosylation 1105:1132 complex type N-glycosylation 1105:1132 The Asn-67 and Asn-91 prodomain sites contained high mannose, whereas complex type N-glycosylation was observed on Asn-436 and Asn-612 in the active and remnant forms. 25336660 10 10 theme Asn-67 1504:1509 arg1 site 1511:1514 the Asn-67 site 1500:1514 the Asn-67 site 1500:1514 In contrast, mutation of the Asn-67 site had only modest effects on enzyme stability and processing. 25336660 10 11 contain had 1516:1518 arg2 effects 1532:1538 only modest effects 1520:1538 only modest effects 1520:1538 In contrast, mutation of the Asn-67 site had only modest effects on enzyme stability and processing. 25336660 10 11 contain had 1516:1518 arg1 mutation 1488:1495 mutation 1488:1495 mutation of the Asn-67 site 1488:1514 In contrast, mutation of the Asn-67 site had only modest effects on enzyme stability and processing. 25336660 1 12 theme transmembrane 63:75 arg1 protein 123:129 The transmembrane ADAM8 (A Disintegrin And Metalloproteinase 8) protein 59:129 The transmembrane ADAM8 (A Disintegrin And Metalloproteinase 8) protein 59:129 The transmembrane ADAM8 (A Disintegrin And Metalloproteinase 8) protein is abundantly expressed in human breast tumors and derived metastases compared with normal breast tissue, and plays critical roles in aggressive Triple-Negative breast cancers (TNBCs). 25336660 5 13 theme ERα-positive 895:906 arg1 ones 908:911 ERα-positive ones 895:911 ERα-positive ones 895:911 Consistently ADAM8 dimers were detected on the surface of ERα-negative breast cancer cells but not on ERα-positive ones. 25336660 7 14 theme complex 1105:1111 arg1 N-glycosylation 1118:1132 complex type N-glycosylation 1105:1132 complex type N-glycosylation 1105:1132 The Asn-67 and Asn-91 prodomain sites contained high mannose, whereas complex type N-glycosylation was observed on Asn-436 and Asn-612 in the active and remnant forms. 25336660 1 15 theme ADAM8 77:81 arg1 protein 123:129 The transmembrane ADAM8 (A Disintegrin And Metalloproteinase 8) protein 59:129 The transmembrane ADAM8 (A Disintegrin And Metalloproteinase 8) protein 59:129 The transmembrane ADAM8 (A Disintegrin And Metalloproteinase 8) protein is abundantly expressed in human breast tumors and derived metastases compared with normal breast tissue, and plays critical roles in aggressive Triple-Negative breast cancers (TNBCs). 25336660 8 16 from reticulum 1359:1367 arg1 exit 1323:1326 particular its exit 1308:1326 particular its exit from the Golgi and endoplasmic reticulum 1308:1367 The Asn-91 and Asn-612 sites were essential for its correct processing and cell surface localization, in particular its exit from the Golgi and endoplasmic reticulum, respectively. 25336660 1 17 theme aggressive 265:274 arg1 cancers 299:305 aggressive Triple-Negative breast cancers 265:305 aggressive Triple-Negative breast cancers (TNBCs) 265:313 The transmembrane ADAM8 (A Disintegrin And Metalloproteinase 8) protein is abundantly expressed in human breast tumors and derived metastases compared with normal breast tissue, and plays critical roles in aggressive Triple-Negative breast cancers (TNBCs). 25336660 1 17 theme aggressive 265:274 arg1 TNBCs 308:312 TNBCs 308:312 TNBCs 308:312 The transmembrane ADAM8 (A Disintegrin And Metalloproteinase 8) protein is abundantly expressed in human breast tumors and derived metastases compared with normal breast tissue, and plays critical roles in aggressive Triple-Negative breast cancers (TNBCs). 25336660 4 18 theme cancer 687:692 arg1 cells 694:698 estrogen receptor (ER)α-negative, but not -positive, breast cancer cells 627:698 estrogen receptor (ER)α-negative, but not -positive, breast cancer cells 627:698 Here, we report that in estrogen receptor (ER)α-negative, but not -positive, breast cancer cells ADAM8 contains N-glycosylation, which is required for its correct processing and activation. 25336660 1 19 link derived 182:188 arg1 metastases 190:199 derived metastases 182:199 derived metastases 182:199 The transmembrane ADAM8 (A Disintegrin And Metalloproteinase 8) protein is abundantly expressed in human breast tumors and derived metastases compared with normal breast tissue, and plays critical roles in aggressive Triple-Negative breast cancers (TNBCs). 25336660 8 20 from essential 1237:1245 arg1 exit 1323:1326 particular its exit 1308:1326 particular its exit from the Golgi and endoplasmic reticulum 1308:1367 The Asn-91 and Asn-612 sites were essential for its correct processing and cell surface localization, in particular its exit from the Golgi and endoplasmic reticulum, respectively. 25336660 8 21 theme particular 1308:1317 arg1 exit 1323:1326 particular its exit 1308:1326 particular its exit from the Golgi and endoplasmic reticulum 1308:1367 The Asn-91 and Asn-612 sites were essential for its correct processing and cell surface localization, in particular its exit from the Golgi and endoplasmic reticulum, respectively. 25336660 8 22 theme Asn-91 1207:1212 arg1 essential 1237:1245 essential 1237:1245 essential 1237:1245 The Asn-91 and Asn-612 sites were essential for its correct processing and cell surface localization, in particular its exit from the Golgi and endoplasmic reticulum, respectively. 25336660 8 22 theme Asn-91 1207:1212 arg1 sites 1226:1230 The Asn-91 and Asn-612 sites 1203:1230 sites 1226:1230 The Asn-91 and Asn-612 sites were essential for its correct processing and cell surface localization, in particular its exit from the Golgi and endoplasmic reticulum, respectively. 25336660 7 23 theme Asn-91 1050:1055 arg1 sites 1067:1071 The Asn-67 and Asn-91 prodomain sites 1035:1071 The Asn-67 and Asn-91 prodomain sites 1035:1071 The Asn-67 and Asn-91 prodomain sites contained high mannose, whereas complex type N-glycosylation was observed on Asn-436 and Asn-612 in the active and remnant forms. 25336660 10 24 theme site 1511:1514 arg1 mutation 1488:1495 mutation 1488:1495 mutation of the Asn-67 site 1488:1514 In contrast, mutation of the Asn-67 site had only modest effects on enzyme stability and processing. 25336660 5 25 theme cancer 871:876 arg1 cells 878:882 ERα-negative breast cancer cells 851:882 ERα-negative breast cancer cells 851:882 Consistently ADAM8 dimers were detected on the surface of ERα-negative breast cancer cells but not on ERα-positive ones. 25336660 4 26 theme correct 758:764 arg1 processing 766:775 its correct processing 754:775 its correct processing 754:775 Here, we report that in estrogen receptor (ER)α-negative, but not -positive, breast cancer cells ADAM8 contains N-glycosylation, which is required for its correct processing and activation. 25336660 1 27 dep protein 123:129 arg1 Metalloproteinase 102:118 Metalloproteinase 8 102:120 Metalloproteinase 8 102:120 The transmembrane ADAM8 (A Disintegrin And Metalloproteinase 8) protein is abundantly expressed in human breast tumors and derived metastases compared with normal breast tissue, and plays critical roles in aggressive Triple-Negative breast cancers (TNBCs). 25336660 1 27 dep protein 123:129 arg1 Disintegrin 86:96 A Disintegrin 84:96 A Disintegrin 84:96 The transmembrane ADAM8 (A Disintegrin And Metalloproteinase 8) protein is abundantly expressed in human breast tumors and derived metastases compared with normal breast tissue, and plays critical roles in aggressive Triple-Negative breast cancers (TNBCs). 25336660 4 28 theme estrogen 627:634 arg1 receptor 636:643 estrogen receptor 627:643 estrogen receptor (ER) 627:648 Here, we report that in estrogen receptor (ER)α-negative, but not -positive, breast cancer cells ADAM8 contains N-glycosylation, which is required for its correct processing and activation. 25336660 4 28 theme estrogen 627:634 arg1 ER 646:647 ER 646:647 ER 646:647 Here, we report that in estrogen receptor (ER)α-negative, but not -positive, breast cancer cells ADAM8 contains N-glycosylation, which is required for its correct processing and activation. 25336660 7 29 theme Asn-67 1039:1044 arg1 sites 1067:1071 The Asn-67 and Asn-91 prodomain sites 1035:1071 The Asn-67 and Asn-91 prodomain sites 1035:1071 The Asn-67 and Asn-91 prodomain sites contained high mannose, whereas complex type N-glycosylation was observed on Asn-436 and Asn-612 in the active and remnant forms. 25336660 6 30 theme N-glycosylazhytion 955:972 arg1 Asn-67 981:986 Asn-67 981:986 Asn-67 981:986 Site-directed mutagenesis confirmed four N-glycosylazhytion sites (Asn-67, Asn-91, Asn-436, and Asn-612) in human ADAM8. 25336660 6 30 theme N-glycosylazhytion 955:972 arg1 sites 974:978 four N-glycosylazhytion sites 950:978 four N-glycosylazhytion sites (Asn-67, Asn-91, Asn-436, and Asn-612) 950:1017 Site-directed mutagenesis confirmed four N-glycosylazhytion sites (Asn-67, Asn-91, Asn-436, and Asn-612) in human ADAM8. 25336660 6 30 theme N-glycosylazhytion 955:972 arg1 Asn-436 997:1003 Asn-436 997:1003 Asn-436 997:1003 Site-directed mutagenesis confirmed four N-glycosylazhytion sites (Asn-67, Asn-91, Asn-436, and Asn-612) in human ADAM8. 25336660 6 30 theme N-glycosylazhytion 955:972 arg1 Asn-612 1010:1016 Asn-612 1010:1016 Asn-612 1010:1016 Site-directed mutagenesis confirmed four N-glycosylazhytion sites (Asn-67, Asn-91, Asn-436, and Asn-612) in human ADAM8. 25336660 6 30 theme N-glycosylazhytion 955:972 arg1 Asn-91 989:994 Asn-91 989:994 Asn-91 989:994 Site-directed mutagenesis confirmed four N-glycosylazhytion sites (Asn-67, Asn-91, Asn-436, and Asn-612) in human ADAM8. 25336660 3 31 dep glycoprotein 499:510 arg1 known 533:537 known 533:537 was known about the structure or functional role of these sugar moieties 529:600 ADAM8 is a glycoprotein; however, little was known about the structure or functional role of these sugar moieties. 25336660 8 32 from Golgi 1337:1341 arg1 exit 1323:1326 particular its exit 1308:1326 particular its exit from the Golgi and endoplasmic reticulum 1308:1367 The Asn-91 and Asn-612 sites were essential for its correct processing and cell surface localization, in particular its exit from the Golgi and endoplasmic reticulum, respectively. 25336660 1 33 theme derived 182:188 arg1 metastases 190:199 derived metastases 182:199 derived metastases 182:199 The transmembrane ADAM8 (A Disintegrin And Metalloproteinase 8) protein is abundantly expressed in human breast tumors and derived metastases compared with normal breast tissue, and plays critical roles in aggressive Triple-Negative breast cancers (TNBCs). 25336660 10 34 theme enzyme 1543:1548 arg1 stability 1550:1558 enzyme stability 1543:1558 enzyme stability 1543:1558 In contrast, mutation of the Asn-67 site had only modest effects on enzyme stability and processing. 25336660 1 35 theme Triple-Negative 276:290 arg1 cancers 299:305 aggressive Triple-Negative breast cancers 265:305 aggressive Triple-Negative breast cancers (TNBCs) 265:313 The transmembrane ADAM8 (A Disintegrin And Metalloproteinase 8) protein is abundantly expressed in human breast tumors and derived metastases compared with normal breast tissue, and plays critical roles in aggressive Triple-Negative breast cancers (TNBCs). 25336660 1 35 theme Triple-Negative 276:290 arg1 TNBCs 308:312 TNBCs 308:312 TNBCs 308:312 The transmembrane ADAM8 (A Disintegrin And Metalloproteinase 8) protein is abundantly expressed in human breast tumors and derived metastases compared with normal breast tissue, and plays critical roles in aggressive Triple-Negative breast cancers (TNBCs). 25336660 3 36 theme functional 562:571 arg1 role 573:576 functional role 562:576 functional role 562:576 ADAM8 is a glycoprotein; however, little was known about the structure or functional role of these sugar moieties. 25336660 6 37 theme human 1022:1026 arg1 ADAM8 1028:1032 human ADAM8 1022:1032 human ADAM8 1022:1032 Site-directed mutagenesis confirmed four N-glycosylazhytion sites (Asn-67, Asn-91, Asn-436, and Asn-612) in human ADAM8. 25336660 1 38 theme breast 292:297 arg1 cancers 299:305 aggressive Triple-Negative breast cancers 265:305 aggressive Triple-Negative breast cancers (TNBCs) 265:313 The transmembrane ADAM8 (A Disintegrin And Metalloproteinase 8) protein is abundantly expressed in human breast tumors and derived metastases compared with normal breast tissue, and plays critical roles in aggressive Triple-Negative breast cancers (TNBCs). 25336660 1 38 theme breast 292:297 arg1 TNBCs 308:312 TNBCs 308:312 TNBCs 308:312 The transmembrane ADAM8 (A Disintegrin And Metalloproteinase 8) protein is abundantly expressed in human breast tumors and derived metastases compared with normal breast tissue, and plays critical roles in aggressive Triple-Negative breast cancers (TNBCs). 25336660 8 39 theme endoplasmic 1347:1357 arg1 reticulum 1359:1367 endoplasmic reticulum 1347:1367 endoplasmic reticulum 1347:1367 The Asn-91 and Asn-612 sites were essential for its correct processing and cell surface localization, in particular its exit from the Golgi and endoplasmic reticulum, respectively. 25336660 8 40 theme cell 1278:1281 arg1 localization 1291:1302 cell surface localization 1278:1302 cell surface localization 1278:1302 The Asn-91 and Asn-612 sites were essential for its correct processing and cell surface localization, in particular its exit from the Golgi and endoplasmic reticulum, respectively. 25336660 8 41 theme Asn-612 1218:1224 arg1 essential 1237:1245 essential 1237:1245 essential 1237:1245 The Asn-91 and Asn-612 sites were essential for its correct processing and cell surface localization, in particular its exit from the Golgi and endoplasmic reticulum, respectively. 25336660 8 41 theme Asn-612 1218:1224 arg1 sites 1226:1230 The Asn-91 and Asn-612 sites 1203:1230 sites 1226:1230 The Asn-91 and Asn-612 sites were essential for its correct processing and cell surface localization, in particular its exit from the Golgi and endoplasmic reticulum, respectively. 25336660 0 42 theme ADAM8 26:30 arg1 processing 32:41 ADAM8 processing 26:41 ADAM8 processing 26:41 N-glycosylation regulates ADAM8 processing and activation. 25336660 9 43 theme lysosomal 1452:1460 arg1 degradation 1462:1472 enhanced lysosomal degradation 1443:1472 enhanced lysosomal degradation 1443:1472 The N436Q mutation led to decreased ADAM8 stability due to enhanced lysosomal degradation. 25336660 2 44 theme inactive 345:352 arg1 proform 354:360 the inactive proform 341:360 the inactive proform 341:360 During ADAM8 maturation, the inactive proform dimerizes or multimerizes and autocatalytically removes the prodomain leading to the formation of the active, processed form. 25336660 5 45 theme ADAM8 806:810 arg1 dimers 812:817 ADAM8 dimers 806:817 ADAM8 dimers 806:817 Consistently ADAM8 dimers were detected on the surface of ERα-negative breast cancer cells but not on ERα-positive ones. 25336660 2 46 theme form 482:485 arg1 formation 447:455 the formation 443:455 the formation of the active, processed form 443:485 During ADAM8 maturation, the inactive proform dimerizes or multimerizes and autocatalytically removes the prodomain leading to the formation of the active, processed form. 25336660 11 47 gly N-glycosylation 1582:1596 arg1 ADAM8 1668:1672 ADAM8 1668:1672 ADAM8 1668:1672 Thus, N-glycosylation is essential for processing, localization, stability, and activity of ADAM8. 25336660 5 48 located detected 824:831 arg2 dimers 812:817 ADAM8 dimers 806:817 ADAM8 dimers 806:817 Consistently ADAM8 dimers were detected on the surface of ERα-negative breast cancer cells but not on ERα-positive ones. 25336660 5 48 located detected 824:831 arg1 surface 840:846 the surface 836:846 the surface of ERα-negative breast cancer cells 836:882 Consistently ADAM8 dimers were detected on the surface of ERα-negative breast cancer cells but not on ERα-positive ones. 25336660 1 49 theme normal 215:220 arg1 tissue 229:234 normal breast tissue 215:234 normal breast tissue 215:234 The transmembrane ADAM8 (A Disintegrin And Metalloproteinase 8) protein is abundantly expressed in human breast tumors and derived metastases compared with normal breast tissue, and plays critical roles in aggressive Triple-Negative breast cancers (TNBCs). 25336660 2 50 theme processed 472:480 arg1 form 482:485 the active, processed form 460:485 form 482:485 During ADAM8 maturation, the inactive proform dimerizes or multimerizes and autocatalytically removes the prodomain leading to the formation of the active, processed form. 25336660 6 51 theme Site-directed 914:926 arg1 mutagenesis 928:938 Site-directed mutagenesis 914:938 Site-directed mutagenesis 914:938 Site-directed mutagenesis confirmed four N-glycosylazhytion sites (Asn-67, Asn-91, Asn-436, and Asn-612) in human ADAM8. 25336660 7 52 theme type 1113:1116 arg1 N-glycosylation 1118:1132 complex type N-glycosylation 1105:1132 complex type N-glycosylation 1105:1132 The Asn-67 and Asn-91 prodomain sites contained high mannose, whereas complex type N-glycosylation was observed on Asn-436 and Asn-612 in the active and remnant forms. 25336660 3 53 theme sugar 587:591 arg1 moieties 593:600 these sugar moieties 581:600 these sugar moieties 581:600 ADAM8 is a glycoprotein; however, little was known about the structure or functional role of these sugar moieties. 25336660 1 54 theme breast 222:227 arg1 tissue 229:234 normal breast tissue 215:234 normal breast tissue 215:234 The transmembrane ADAM8 (A Disintegrin And Metalloproteinase 8) protein is abundantly expressed in human breast tumors and derived metastases compared with normal breast tissue, and plays critical roles in aggressive Triple-Negative breast cancers (TNBCs). 25336660 8 55 dep Golgi 1337:1341 arg1 the 1333:1335 the 1333:1335 the 1333:1335 The Asn-91 and Asn-612 sites were essential for its correct processing and cell surface localization, in particular its exit from the Golgi and endoplasmic reticulum, respectively. 25336660 4 56 contain contains 706:713 arg1 ADAM8 700:704 ADAM8 700:704 ADAM8 700:704 Here, we report that in estrogen receptor (ER)α-negative, but not -positive, breast cancer cells ADAM8 contains N-glycosylation, which is required for its correct processing and activation. 25336660 4 56 contain contains 706:713 arg2 ADAM8 700:704 ADAM8 700:704 ADAM8 700:704 Here, we report that in estrogen receptor (ER)α-negative, but not -positive, breast cancer cells ADAM8 contains N-glycosylation, which is required for its correct processing and activation. 25336660 4 56 contain contains 706:713 arg2 N-glycosylation 715:729 N-glycosylation 715:729 N-glycosylation 715:729 Here, we report that in estrogen receptor (ER)α-negative, but not -positive, breast cancer cells ADAM8 contains N-glycosylation, which is required for its correct processing and activation. 25336660 4 56 contain contains 706:713 arg1 cells 694:698 estrogen receptor (ER)α-negative, but not -positive, breast cancer cells 627:698 estrogen receptor (ER)α-negative, but not -positive, breast cancer cells 627:698 Here, we report that in estrogen receptor (ER)α-negative, but not -positive, breast cancer cells ADAM8 contains N-glycosylation, which is required for its correct processing and activation. 25336660 9 57 theme N436Q 1388:1392 arg1 mutation 1394:1401 The N436Q mutation 1384:1401 The N436Q mutation 1384:1401 The N436Q mutation led to decreased ADAM8 stability due to enhanced lysosomal degradation. 25336660 4 58 theme -positive 669:677 arg1 cells 694:698 estrogen receptor (ER)α-negative, but not -positive, breast cancer cells 627:698 estrogen receptor (ER)α-negative, but not -positive, breast cancer cells 627:698 Here, we report that in estrogen receptor (ER)α-negative, but not -positive, breast cancer cells ADAM8 contains N-glycosylation, which is required for its correct processing and activation. 25336660 2 59 theme active 464:469 arg1 form 482:485 the active, processed form 460:485 form 482:485 During ADAM8 maturation, the inactive proform dimerizes or multimerizes and autocatalytically removes the prodomain leading to the formation of the active, processed form. 25336660 11 60 theme ADAM8 1668:1672 arg1 processing 1615:1624 processing 1615:1624 processing 1615:1624 Thus, N-glycosylation is essential for processing, localization, stability, and activity of ADAM8. 25336660 11 60 theme ADAM8 1668:1672 arg1 stability 1641:1649 stability 1641:1649 stability 1641:1649 Thus, N-glycosylation is essential for processing, localization, stability, and activity of ADAM8. 25336660 11 60 theme ADAM8 1668:1672 arg1 activity 1656:1663 activity 1656:1663 activity 1656:1663 Thus, N-glycosylation is essential for processing, localization, stability, and activity of ADAM8. 25336660 11 60 theme ADAM8 1668:1672 arg1 localization 1627:1638 localization 1627:1638 localization 1627:1638 Thus, N-glycosylation is essential for processing, localization, stability, and activity of ADAM8. 25336660 7 61 theme prodomain 1057:1065 arg1 sites 1067:1071 The Asn-67 and Asn-91 prodomain sites 1035:1071 The Asn-67 and Asn-91 prodomain sites 1035:1071 The Asn-67 and Asn-91 prodomain sites contained high mannose, whereas complex type N-glycosylation was observed on Asn-436 and Asn-612 in the active and remnant forms. 25336660 9 62 theme ADAM8 1420:1424 arg1 stability 1426:1434 decreased ADAM8 stability 1410:1434 decreased ADAM8 stability 1410:1434 The N436Q mutation led to decreased ADAM8 stability due to enhanced lysosomal degradation. 25336660 9 63 theme enhanced 1443:1450 arg1 degradation 1462:1472 enhanced lysosomal degradation 1443:1472 enhanced lysosomal degradation 1443:1472 The N436Q mutation led to decreased ADAM8 stability due to enhanced lysosomal degradation. 25336660 4 64 theme breast 680:685 arg1 cells 694:698 estrogen receptor (ER)α-negative, but not -positive, breast cancer cells 627:698 estrogen receptor (ER)α-negative, but not -positive, breast cancer cells 627:698 Here, we report that in estrogen receptor (ER)α-negative, but not -positive, breast cancer cells ADAM8 contains N-glycosylation, which is required for its correct processing and activation. 25336660 3 65 gly glycoprotein 499:510 arg1 ADAM8 488:492 ADAM8 488:492 ADAM8 488:492 ADAM8 is a glycoprotein; however, little was known about the structure or functional role of these sugar moieties. 25336660 3 65 gly glycoprotein 499:510 arg1 glycoprotein 499:510 a glycoprotein 497:510 a glycoprotein; however, little was known about the structure or functional role of these sugar moieties 497:600 ADAM8 is a glycoprotein; however, little was known about the structure or functional role of these sugar moieties. 25336660 5 66 theme cells 878:882 arg1 surface 840:846 the surface 836:846 the surface of ERα-negative breast cancer cells 836:882 Consistently ADAM8 dimers were detected on the surface of ERα-negative breast cancer cells but not on ERα-positive ones. 25336660 2 67 theme ADAM8 323:327 arg1 maturation 329:338 ADAM8 maturation 323:338 ADAM8 maturation 323:338 During ADAM8 maturation, the inactive proform dimerizes or multimerizes and autocatalytically removes the prodomain leading to the formation of the active, processed form. 25336660 8 68 theme surface 1283:1289 arg1 localization 1291:1302 cell surface localization 1278:1302 cell surface localization 1278:1302 The Asn-91 and Asn-612 sites were essential for its correct processing and cell surface localization, in particular its exit from the Golgi and endoplasmic reticulum, respectively. 25336660 8 69 theme correct 1255:1261 arg1 processing 1263:1272 its correct processing 1251:1272 its correct processing 1251:1272 The Asn-91 and Asn-612 sites were essential for its correct processing and cell surface localization, in particular its exit from the Golgi and endoplasmic reticulum, respectively. 25336660 4 70 gly N-glycosylation 715:729 arg1 cells 694:698 estrogen receptor (ER)α-negative, but not -positive, breast cancer cells 627:698 estrogen receptor (ER)α-negative, but not -positive, breast cancer cells 627:698 Here, we report that in estrogen receptor (ER)α-negative, but not -positive, breast cancer cells ADAM8 contains N-glycosylation, which is required for its correct processing and activation. 25336660 5 71 theme ERα-negative 851:862 arg1 cells 878:882 ERα-negative breast cancer cells 851:882 ERα-negative breast cancer cells 851:882 Consistently ADAM8 dimers were detected on the surface of ERα-negative breast cancer cells but not on ERα-positive ones. 25336660 3 72 theme moieties 593:600 arg1 structure 549:557 structure 549:557 structure 549:557 ADAM8 is a glycoprotein; however, little was known about the structure or functional role of these sugar moieties. 25336660 3 72 theme moieties 593:600 arg1 role 573:576 functional role 562:576 functional role 562:576 ADAM8 is a glycoprotein; however, little was known about the structure or functional role of these sugar moieties. 25336660 9 73 theme decreased 1410:1418 arg1 stability 1426:1434 decreased ADAM8 stability 1410:1434 decreased ADAM8 stability 1410:1434 The N436Q mutation led to decreased ADAM8 stability due to enhanced lysosomal degradation. 25336660 4 74 theme α-negative 649:658 arg1 cells 694:698 estrogen receptor (ER)α-negative, but not -positive, breast cancer cells 627:698 estrogen receptor (ER)α-negative, but not -positive, breast cancer cells 627:698 Here, we report that in estrogen receptor (ER)α-negative, but not -positive, breast cancer cells ADAM8 contains N-glycosylation, which is required for its correct processing and activation. 25336660 7 75 theme remnant 1188:1194 arg1 forms 1196:1200 the active and remnant forms 1173:1200 the active and remnant forms 1173:1200 The Asn-67 and Asn-91 prodomain sites contained high mannose, whereas complex type N-glycosylation was observed on Asn-436 and Asn-612 in the active and remnant forms. 25336660 7 76 gly N-glycosylation 1118:1132 arg1 Asn-612 1162:1168 Asn-612 1162:1168 Asn-612 1162:1168 The Asn-67 and Asn-91 prodomain sites contained high mannose, whereas complex type N-glycosylation was observed on Asn-436 and Asn-612 in the active and remnant forms. 25336660 7 76 gly N-glycosylation 1118:1132 arg1 Asn-436 1150:1156 Asn-436 1150:1156 Asn-436 1150:1156 The Asn-67 and Asn-91 prodomain sites contained high mannose, whereas complex type N-glycosylation was observed on Asn-436 and Asn-612 in the active and remnant forms. 25336660 7 76 gly N-glycosylation 1118:1132 arg1 forms 1196:1200 the active and remnant forms 1173:1200 the active and remnant forms 1173:1200 The Asn-67 and Asn-91 prodomain sites contained high mannose, whereas complex type N-glycosylation was observed on Asn-436 and Asn-612 in the active and remnant forms. 25336660 3 77 dep structure 549:557 arg1 the 545:547 the 545:547 the 545:547 ADAM8 is a glycoprotein; however, little was known about the structure or functional role of these sugar moieties. 25336660 7 78 contain contained 1073:1081 arg2 mannose 1088:1094 high mannose 1083:1094 high mannose 1083:1094 The Asn-67 and Asn-91 prodomain sites contained high mannose, whereas complex type N-glycosylation was observed on Asn-436 and Asn-612 in the active and remnant forms. 25336660 7 78 contain contained 1073:1081 arg1 sites 1067:1071 The Asn-67 and Asn-91 prodomain sites 1035:1071 The Asn-67 and Asn-91 prodomain sites 1035:1071 The Asn-67 and Asn-91 prodomain sites contained high mannose, whereas complex type N-glycosylation was observed on Asn-436 and Asn-612 in the active and remnant forms. 28315854 0 0 theme cancer 77:82 arg1 cells 84:88 breast cancer cells 70:88 breast cancer cells 70:88 Mutation of N-linked glycosylation in EpCAM affected cell adhesion in breast cancer cells. 28315854 8 1 theme cancer 1186:1191 arg1 therapy 1193:1199 breast cancer therapy 1179:1199 breast cancer therapy 1179:1199 These data could potentially clarify molecular regulation of EpCAM by N-glycosylation and intensify our understanding of the utility of glycosylated EpCAM as a target for breast cancer therapy. 28315854 8 2 theme EpCAM 1069:1073 arg1 regulation 1055:1064 molecular regulation 1045:1064 molecular regulation of EpCAM by N-glycosylation 1045:1092 These data could potentially clarify molecular regulation of EpCAM by N-glycosylation and intensify our understanding of the utility of glycosylated EpCAM as a target for breast cancer therapy. 28315854 8 3 theme EpCAM 1157:1161 arg1 utility 1133:1139 the utility 1129:1139 the utility of glycosylated EpCAM as a target for breast cancer therapy 1129:1199 These data could potentially clarify molecular regulation of EpCAM by N-glycosylation and intensify our understanding of the utility of glycosylated EpCAM as a target for breast cancer therapy. 28315854 1 4 theme cell 227:230 arg1 adhesion 232:239 cell adhesion 227:239 cell adhesion 227:239 Epithelial cell adhesion molecule (EpCAM) expression is elevated in breast cancer tissue, and correlates with the cancer metastasis and cell adhesion. 28315854 0 5 theme breast 70:75 arg1 cells 84:88 breast cancer cells 70:88 breast cancer cells 70:88 Mutation of N-linked glycosylation in EpCAM affected cell adhesion in breast cancer cells. 28315854 5 6 theme lower 656:660 arg1 levels 662:667 lower levels 656:667 lower levels of integrin β1 and fibronectin 656:698 N-glycosylation mutation of EpCAM was correlated with lower levels of integrin β1 and fibronectin. 28315854 7 7 theme cell 993:996 arg1 adhesion 998:1005 breast cancer cell adhesion 979:1005 breast cancer cell adhesion 979:1005 Our studies identified the characteristics and function of EpCAM glycosylation sites on breast cancer cell adhesion. 28315854 0 8 from Mutation 0:7 arg1 EpCAM 38:42 EpCAM 38:42 EpCAM 38:42 Mutation of N-linked glycosylation in EpCAM affected cell adhesion in breast cancer cells. 28315854 0 9 link N-linked 12:19 arg1 glycosylation 21:33 N-linked glycosylation 12:33 N-linked glycosylation 12:33 Mutation of N-linked glycosylation in EpCAM affected cell adhesion in breast cancer cells. 28315854 4 10 theme adhesion 583:590 arg1 capacity 592:599 adhesion capacity 583:599 adhesion capacity 583:599 The results showed that EpCAM expression was associated with cell adhesion and N-glycosylation mutation of EpCAM decreased adhesion capacity. 28315854 5 11 theme N-glycosylation 602:616 arg1 mutation 618:625 N-glycosylation mutation 602:625 N-glycosylation mutation of EpCAM 602:634 N-glycosylation mutation of EpCAM was correlated with lower levels of integrin β1 and fibronectin. 28315854 6 12 theme FAK/Akt/Gsk-3β/β-catenin 790:813 arg1 pathway 825:831 FAK/Akt/Gsk-3β/β-catenin signaling pathway 790:831 FAK/Akt/Gsk-3β/β-catenin signaling pathway 790:831 We also found that effect of N-glycosylation of EpCAM on cell adhesion was regulated via FAK/Akt/Gsk-3β/β-catenin signaling pathway, which further adjusted MMP2/9 expression and activities. 28315854 3 13 theme cell 405:408 arg1 ability 419:425 cell adhesion ability 405:425 cell adhesion ability of EpCAM 405:434 Here we analyzed cell adhesion ability of EpCAM in breast cancer cells. 28315854 4 14 theme EpCAM 567:571 arg1 mutation 555:562 N-glycosylation mutation 539:562 N-glycosylation mutation of EpCAM 539:571 The results showed that EpCAM expression was associated with cell adhesion and N-glycosylation mutation of EpCAM decreased adhesion capacity. 28315854 7 15 theme sites 970:974 arg1 function 938:945 function 938:945 function 938:945 Our studies identified the characteristics and function of EpCAM glycosylation sites on breast cancer cell adhesion. 28315854 7 15 theme sites 970:974 arg1 characteristics 918:932 characteristics 918:932 characteristics 918:932 Our studies identified the characteristics and function of EpCAM glycosylation sites on breast cancer cell adhesion. 28315854 2 16 theme EpCAM 251:255 arg1 glycosylation 257:269 EpCAM glycosylation 251:269 EpCAM glycosylation 251:269 Although EpCAM glycosylation is supposed to be associated with its function, the contribution of N-glycosylation to its function remains unclear. 28315854 1 17 theme breast 159:164 arg1 tissue 173:178 breast cancer tissue 159:178 breast cancer tissue 159:178 Epithelial cell adhesion molecule (EpCAM) expression is elevated in breast cancer tissue, and correlates with the cancer metastasis and cell adhesion. 28315854 7 18 theme breast 979:984 arg1 adhesion 998:1005 breast cancer cell adhesion 979:1005 breast cancer cell adhesion 979:1005 Our studies identified the characteristics and function of EpCAM glycosylation sites on breast cancer cell adhesion. 28315854 8 19 theme breast 1179:1184 arg1 therapy 1193:1199 breast cancer therapy 1179:1199 breast cancer therapy 1179:1199 These data could potentially clarify molecular regulation of EpCAM by N-glycosylation and intensify our understanding of the utility of glycosylated EpCAM as a target for breast cancer therapy. 28315854 8 20 theme glycosylated 1144:1155 arg1 EpCAM 1157:1161 glycosylated EpCAM 1144:1161 glycosylated EpCAM 1144:1161 These data could potentially clarify molecular regulation of EpCAM by N-glycosylation and intensify our understanding of the utility of glycosylated EpCAM as a target for breast cancer therapy. 28315854 1 21 theme cancer 166:171 arg1 tissue 173:178 breast cancer tissue 159:178 breast cancer tissue 159:178 Epithelial cell adhesion molecule (EpCAM) expression is elevated in breast cancer tissue, and correlates with the cancer metastasis and cell adhesion. 28315854 7 22 theme EpCAM 950:954 arg1 sites 970:974 EpCAM glycosylation sites 950:974 EpCAM glycosylation sites 950:974 Our studies identified the characteristics and function of EpCAM glycosylation sites on breast cancer cell adhesion. 28315854 8 23 gly glycosylated 1144:1155 arg1 EpCAM 1157:1161 glycosylated EpCAM 1144:1161 glycosylated EpCAM 1144:1161 These data could potentially clarify molecular regulation of EpCAM by N-glycosylation and intensify our understanding of the utility of glycosylated EpCAM as a target for breast cancer therapy. 28315854 3 24 theme adhesion 410:417 arg1 ability 419:425 cell adhesion ability 405:425 cell adhesion ability of EpCAM 405:434 Here we analyzed cell adhesion ability of EpCAM in breast cancer cells. 28315854 0 25 theme glycosylation 21:33 arg1 Mutation 0:7 Mutation 0:7 Mutation of N-linked glycosylation in EpCAM 0:42 Mutation of N-linked glycosylation in EpCAM affected cell adhesion in breast cancer cells. 28315854 7 26 theme glycosylation 956:968 arg1 sites 970:974 EpCAM glycosylation sites 950:974 EpCAM glycosylation sites 950:974 Our studies identified the characteristics and function of EpCAM glycosylation sites on breast cancer cell adhesion. 28315854 1 27 theme Epithelial 91:100 arg1 EpCAM 126:130 EpCAM 126:130 EpCAM 126:130 Epithelial cell adhesion molecule (EpCAM) expression is elevated in breast cancer tissue, and correlates with the cancer metastasis and cell adhesion. 28315854 1 27 theme Epithelial 91:100 arg1 molecule 116:123 Epithelial cell adhesion molecule 91:123 Epithelial cell adhesion molecule (EpCAM) expression 91:142 Epithelial cell adhesion molecule (EpCAM) expression is elevated in breast cancer tissue, and correlates with the cancer metastasis and cell adhesion. 28315854 7 28 dep characteristics 918:932 arg1 the 914:916 the 914:916 the 914:916 Our studies identified the characteristics and function of EpCAM glycosylation sites on breast cancer cell adhesion. 28315854 3 29 theme breast 439:444 arg1 cells 453:457 breast cancer cells 439:457 breast cancer cells 439:457 Here we analyzed cell adhesion ability of EpCAM in breast cancer cells. 28315854 0 30 theme N-linked 12:19 arg1 glycosylation 21:33 N-linked glycosylation 12:33 N-linked glycosylation 12:33 Mutation of N-linked glycosylation in EpCAM affected cell adhesion in breast cancer cells. 28315854 1 31 dep metastasis 212:221 arg1 the 201:203 the 201:203 the 201:203 Epithelial cell adhesion molecule (EpCAM) expression is elevated in breast cancer tissue, and correlates with the cancer metastasis and cell adhesion. 28315854 1 32 theme cell 102:105 arg1 EpCAM 126:130 EpCAM 126:130 EpCAM 126:130 Epithelial cell adhesion molecule (EpCAM) expression is elevated in breast cancer tissue, and correlates with the cancer metastasis and cell adhesion. 28315854 1 32 theme cell 102:105 arg1 molecule 116:123 Epithelial cell adhesion molecule 91:123 Epithelial cell adhesion molecule (EpCAM) expression 91:142 Epithelial cell adhesion molecule (EpCAM) expression is elevated in breast cancer tissue, and correlates with the cancer metastasis and cell adhesion. 28315854 6 33 theme signaling 815:823 arg1 pathway 825:831 FAK/Akt/Gsk-3β/β-catenin signaling pathway 790:831 FAK/Akt/Gsk-3β/β-catenin signaling pathway 790:831 We also found that effect of N-glycosylation of EpCAM on cell adhesion was regulated via FAK/Akt/Gsk-3β/β-catenin signaling pathway, which further adjusted MMP2/9 expression and activities. 28315854 3 34 theme cancer 446:451 arg1 cells 453:457 breast cancer cells 439:457 breast cancer cells 439:457 Here we analyzed cell adhesion ability of EpCAM in breast cancer cells. 28315854 4 35 theme N-glycosylation 539:553 arg1 mutation 555:562 N-glycosylation mutation 539:562 N-glycosylation mutation of EpCAM 539:571 The results showed that EpCAM expression was associated with cell adhesion and N-glycosylation mutation of EpCAM decreased adhesion capacity. 28315854 7 36 theme cancer 986:991 arg1 adhesion 998:1005 breast cancer cell adhesion 979:1005 breast cancer cell adhesion 979:1005 Our studies identified the characteristics and function of EpCAM glycosylation sites on breast cancer cell adhesion. 28315854 3 37 theme EpCAM 430:434 arg1 ability 419:425 cell adhesion ability 405:425 cell adhesion ability of EpCAM 405:434 Here we analyzed cell adhesion ability of EpCAM in breast cancer cells. 28315854 8 38 theme utility 1133:1139 arg1 understanding 1112:1124 our understanding 1108:1124 our understanding of the utility of glycosylated EpCAM as a target for breast cancer therapy 1108:1199 These data could potentially clarify molecular regulation of EpCAM by N-glycosylation and intensify our understanding of the utility of glycosylated EpCAM as a target for breast cancer therapy. 28315854 6 39 theme cell 758:761 arg1 adhesion 763:770 cell adhesion 758:770 cell adhesion 758:770 We also found that effect of N-glycosylation of EpCAM on cell adhesion was regulated via FAK/Akt/Gsk-3β/β-catenin signaling pathway, which further adjusted MMP2/9 expression and activities. 28315854 0 40 theme cell 53:56 arg1 adhesion 58:65 cell adhesion 53:65 cell adhesion 53:65 Mutation of N-linked glycosylation in EpCAM affected cell adhesion in breast cancer cells. 28315854 5 41 theme integrin 672:679 arg1 β1 681:682 integrin β1 672:682 integrin β1 672:682 N-glycosylation mutation of EpCAM was correlated with lower levels of integrin β1 and fibronectin. 28315854 1 42 theme adhesion 107:114 arg1 EpCAM 126:130 EpCAM 126:130 EpCAM 126:130 Epithelial cell adhesion molecule (EpCAM) expression is elevated in breast cancer tissue, and correlates with the cancer metastasis and cell adhesion. 28315854 1 42 theme adhesion 107:114 arg1 molecule 116:123 Epithelial cell adhesion molecule 91:123 Epithelial cell adhesion molecule (EpCAM) expression 91:142 Epithelial cell adhesion molecule (EpCAM) expression is elevated in breast cancer tissue, and correlates with the cancer metastasis and cell adhesion. 28315854 4 43 theme EpCAM 484:488 arg1 expression 490:499 EpCAM expression 484:499 EpCAM expression 484:499 The results showed that EpCAM expression was associated with cell adhesion and N-glycosylation mutation of EpCAM decreased adhesion capacity. 28315854 4 44 theme cell 521:524 arg1 adhesion 526:533 cell adhesion 521:533 cell adhesion 521:533 The results showed that EpCAM expression was associated with cell adhesion and N-glycosylation mutation of EpCAM decreased adhesion capacity. 28315854 5 45 theme β1 681:682 arg1 levels 662:667 lower levels 656:667 lower levels of integrin β1 and fibronectin 656:698 N-glycosylation mutation of EpCAM was correlated with lower levels of integrin β1 and fibronectin. 28315854 6 46 theme MMP2/9 857:862 arg1 expression 864:873 MMP2/9 expression 857:873 MMP2/9 expression 857:873 We also found that effect of N-glycosylation of EpCAM on cell adhesion was regulated via FAK/Akt/Gsk-3β/β-catenin signaling pathway, which further adjusted MMP2/9 expression and activities. 28315854 5 47 theme EpCAM 630:634 arg1 mutation 618:625 N-glycosylation mutation 602:625 N-glycosylation mutation of EpCAM 602:634 N-glycosylation mutation of EpCAM was correlated with lower levels of integrin β1 and fibronectin. 28315854 6 48 theme EpCAM 749:753 arg1 N-glycosylation 730:744 N-glycosylation 730:744 N-glycosylation of EpCAM 730:753 We also found that effect of N-glycosylation of EpCAM on cell adhesion was regulated via FAK/Akt/Gsk-3β/β-catenin signaling pathway, which further adjusted MMP2/9 expression and activities. 28315854 1 49 theme molecule 116:123 arg1 expression 133:142 Epithelial cell adhesion molecule (EpCAM) expression 91:142 Epithelial cell adhesion molecule (EpCAM) expression 91:142 Epithelial cell adhesion molecule (EpCAM) expression is elevated in breast cancer tissue, and correlates with the cancer metastasis and cell adhesion. 28315854 8 50 theme molecular 1045:1053 arg1 regulation 1055:1064 molecular regulation 1045:1064 molecular regulation of EpCAM by N-glycosylation 1045:1092 These data could potentially clarify molecular regulation of EpCAM by N-glycosylation and intensify our understanding of the utility of glycosylated EpCAM as a target for breast cancer therapy. 28315854 5 51 theme fibronectin 688:698 arg1 levels 662:667 lower levels 656:667 lower levels of integrin β1 and fibronectin 656:698 N-glycosylation mutation of EpCAM was correlated with lower levels of integrin β1 and fibronectin. 28315854 6 52 theme N-glycosylation 730:744 arg1 effect 720:725 effect 720:725 effect of N-glycosylation of EpCAM on cell adhesion 720:770 We also found that effect of N-glycosylation of EpCAM on cell adhesion was regulated via FAK/Akt/Gsk-3β/β-catenin signaling pathway, which further adjusted MMP2/9 expression and activities. 28315854 1 53 theme cancer 205:210 arg1 metastasis 212:221 cancer metastasis 205:221 cancer metastasis 205:221 Epithelial cell adhesion molecule (EpCAM) expression is elevated in breast cancer tissue, and correlates with the cancer metastasis and cell adhesion. 28315854 6 54 from effect 720:725 arg1 adhesion 763:770 cell adhesion 758:770 cell adhesion 758:770 We also found that effect of N-glycosylation of EpCAM on cell adhesion was regulated via FAK/Akt/Gsk-3β/β-catenin signaling pathway, which further adjusted MMP2/9 expression and activities. 28315854 6 55 gly N-glycosylation 730:744 arg1 EpCAM 749:753 EpCAM 749:753 EpCAM 749:753 We also found that effect of N-glycosylation of EpCAM on cell adhesion was regulated via FAK/Akt/Gsk-3β/β-catenin signaling pathway, which further adjusted MMP2/9 expression and activities. 28315854 6 55 gly N-glycosylation 730:744 arg1 cell 758:761 cell adhesion 758:770 cell adhesion 758:770 We also found that effect of N-glycosylation of EpCAM on cell adhesion was regulated via FAK/Akt/Gsk-3β/β-catenin signaling pathway, which further adjusted MMP2/9 expression and activities. 28315854 7 56 gly glycosylation 956:968 arg2 sites 970:974 EpCAM glycosylation sites 950:974 EpCAM glycosylation sites 950:974 Our studies identified the characteristics and function of EpCAM glycosylation sites on breast cancer cell adhesion. 28315854 2 57 theme N-glycosylation 339:353 arg1 contribution 323:334 the contribution 319:334 the contribution of N-glycosylation to its function 319:369 Although EpCAM glycosylation is supposed to be associated with its function, the contribution of N-glycosylation to its function remains unclear. 24899172 9 0 theme virion 1822:1827 arg1 secretion 1829:1837 HBV virion secretion 1818:1837 HBV virion secretion 1818:1837 Taken together, these findings suggest that the nonglycosylated N146 is essential for infectivity, while the glycosylated form, in addition to its importance for HBV virion secretion, is instrumental in shielding the a-determinant from neutralizing antibodies. 24899172 3 1 gly glycosylated 635:646 arg1 isoforms 668:675 the glycosylated and nonglycosylated isoforms 631:675 the glycosylated and nonglycosylated isoforms 631:675 Here we investigated the requirement for a precise positioning of N-linked glycan at amino acid 146 and the functions associated with the glycosylated and nonglycosylated isoforms. 24899172 8 2 theme neutralizing 1631:1642 arg1 antibodies 1644:1653 neutralizing antibodies 1631:1653 neutralizing antibodies 1631:1653 Infectivity-compatible N-glycosylation sites could be inserted at 3 positions (positions 115, 129, and 136), but when all three positions were glycosylated, the hyperglycosylated mutant was substantially attenuated at viral entry, while it acquired resistance to neutralizing antibodies. 24899172 1 3 theme N-linked 240:247 arg1 site 263:266 an N-linked glycosylation site 237:266 an N-linked glycosylation site at N146 within the immunodominant a-determinant in the antigenic loop (AGL) region 237:349 The envelope proteins of hepatitis B virus (HBV) bear an N-linked glycosylation site at N146 within the immunodominant a-determinant in the antigenic loop (AGL) region. 24899172 4 4 theme delta 872:876 arg1 HDV 885:887 HDV 885:887 HDV 885:887 We observed that the removal of the N146 glycosylation site by mutagenesis was permissive to envelope protein synthesis and stability and to secretion of subviral particles (SVPs) and hepatitis delta virus (HDV) virions, but it was detrimental to HBV virion production. 24899172 4 4 theme delta 872:876 arg1 virus 878:882 hepatitis delta virus 862:882 hepatitis delta virus (HDV) virions 862:896 We observed that the removal of the N146 glycosylation site by mutagenesis was permissive to envelope protein synthesis and stability and to secretion of subviral particles (SVPs) and hepatitis delta virus (HDV) virions, but it was detrimental to HBV virion production. 24899172 10 5 theme antibodies 2030:2039 arg1 IMPORTANCE 1917:1926 IMPORTANCE 1917:1926 IMPORTANCE 1917:1926 IMPORTANCE: At the surface of HBV particles, the immunodominant a-determinant is the main target of neutralizing antibodies and an essential determinant of infectivity. 24899172 10 5 theme antibodies 2030:2039 arg1 a-determinant 1981:1993 the immunodominant a-determinant 1962:1993 the immunodominant a-determinant 1962:1993 IMPORTANCE: At the surface of HBV particles, the immunodominant a-determinant is the main target of neutralizing antibodies and an essential determinant of infectivity. 24899172 10 5 theme antibodies 2030:2039 arg1 determinant 2058:2068 an essential determinant 2045:2068 an essential determinant of infectivity 2045:2083 IMPORTANCE: At the surface of HBV particles, the immunodominant a-determinant is the main target of neutralizing antibodies and an essential determinant of infectivity. 24899172 10 5 theme antibodies 2030:2039 arg1 target 2007:2012 the main target 1998:2012 the main target of neutralizing antibodies 1998:2039 IMPORTANCE: At the surface of HBV particles, the immunodominant a-determinant is the main target of neutralizing antibodies and an essential determinant of infectivity. 24899172 8 6 theme viral 1586:1590 arg1 entry 1592:1596 viral entry 1586:1596 viral entry 1586:1596 Infectivity-compatible N-glycosylation sites could be inserted at 3 positions (positions 115, 129, and 136), but when all three positions were glycosylated, the hyperglycosylated mutant was substantially attenuated at viral entry, while it acquired resistance to neutralizing antibodies. 24899172 1 7 from a-determinant 302:314 arg1 region 344:349 the antigenic loop (AGL) region 319:349 the antigenic loop (AGL) region 319:349 The envelope proteins of hepatitis B virus (HBV) bear an N-linked glycosylation site at N146 within the immunodominant a-determinant in the antigenic loop (AGL) region. 24899172 4 8 theme particles 841:849 arg1 secretion 819:827 secretion 819:827 secretion of subviral particles (SVPs) and hepatitis delta virus (HDV) virions 819:896 We observed that the removal of the N146 glycosylation site by mutagenesis was permissive to envelope protein synthesis and stability and to secretion of subviral particles (SVPs) and hepatitis delta virus (HDV) virions, but it was detrimental to HBV virion production. 24899172 10 9 theme infectivity 2073:2083 arg1 IMPORTANCE 1917:1926 IMPORTANCE 1917:1926 IMPORTANCE 1917:1926 IMPORTANCE: At the surface of HBV particles, the immunodominant a-determinant is the main target of neutralizing antibodies and an essential determinant of infectivity. 24899172 10 9 theme infectivity 2073:2083 arg1 a-determinant 1981:1993 the immunodominant a-determinant 1962:1993 the immunodominant a-determinant 1962:1993 IMPORTANCE: At the surface of HBV particles, the immunodominant a-determinant is the main target of neutralizing antibodies and an essential determinant of infectivity. 24899172 10 9 theme infectivity 2073:2083 arg1 determinant 2058:2068 an essential determinant 2045:2068 an essential determinant of infectivity 2045:2083 IMPORTANCE: At the surface of HBV particles, the immunodominant a-determinant is the main target of neutralizing antibodies and an essential determinant of infectivity. 24899172 10 9 theme infectivity 2073:2083 arg1 target 2007:2012 the main target 1998:2012 the main target of neutralizing antibodies 1998:2039 IMPORTANCE: At the surface of HBV particles, the immunodominant a-determinant is the main target of neutralizing antibodies and an essential determinant of infectivity. 24899172 11 10 contain contains 2089:2096 arg2 functional 2148:2157 functional 2148:2157 functional 2148:2157 It contains an N-glycosylation site at position 146, which is functional on only half of the envelope proteins. 24899172 11 10 contain contains 2089:2096 arg2 site 2117:2120 an N-glycosylation site 2098:2120 an N-glycosylation site 2098:2120 It contains an N-glycosylation site at position 146, which is functional on only half of the envelope proteins. 24899172 11 10 contain contains 2089:2096 arg1 It 2086:2087 It 2086:2087 It 2086:2087 It contains an N-glycosylation site at position 146, which is functional on only half of the envelope proteins. 24899172 11 11 from position 2125:2132 arg1 site 2117:2120 an N-glycosylation site 2098:2120 an N-glycosylation site 2098:2120 It contains an N-glycosylation site at position 146, which is functional on only half of the envelope proteins. 24899172 11 11 from position 2125:2132 arg1 functional 2148:2157 functional 2148:2157 functional 2148:2157 It contains an N-glycosylation site at position 146, which is functional on only half of the envelope proteins. 24899172 13 12 theme virion 2452:2457 arg1 assembly 2459:2466 virion assembly 2452:2466 virion assembly 2452:2466 Hence, a modification of the HBV glycosylation pattern affects not only virion assembly and infectivity but also immune escape. 24899172 5 13 from positions 956:964 arg1 AGL 973:975 the AGL 969:975 the AGL 969:975 Several positions in the AGL could substitute for position 146 as the glycosylation acceptor site. 24899172 7 14 theme virion 1350:1355 arg1 secretion 1357:1365 HDV virion secretion 1346:1365 HDV virion secretion 1346:1365 Envelope proteins bearing 5 AGL glycosylation sites became hyperglycosylated, leading to an increased capacity for SVP secretion at the expense of HBV and HDV virion secretion. 24899172 1 15 from N146 271:274 arg1 site 263:266 an N-linked glycosylation site 237:266 an N-linked glycosylation site at N146 within the immunodominant a-determinant in the antigenic loop (AGL) region 237:349 The envelope proteins of hepatitis B virus (HBV) bear an N-linked glycosylation site at N146 within the immunodominant a-determinant in the antigenic loop (AGL) region. 24899172 3 16 theme N-linked 563:570 arg1 glycan 572:577 N-linked glycan 563:577 N-linked glycan 563:577 Here we investigated the requirement for a precise positioning of N-linked glycan at amino acid 146 and the functions associated with the glycosylated and nonglycosylated isoforms. 24899172 13 17 theme pattern 2427:2433 arg1 modification 2389:2400 a modification 2387:2400 a modification of the HBV glycosylation pattern 2387:2433 Hence, a modification of the HBV glycosylation pattern affects not only virion assembly and infectivity but also immune escape. 24899172 5 18 theme acceptor 1032:1039 arg1 site 1041:1044 the glycosylation acceptor site 1014:1044 the glycosylation acceptor site 1014:1044 Several positions in the AGL could substitute for position 146 as the glycosylation acceptor site. 24899172 1 19 theme hepatitis 208:216 arg1 HBV 227:229 HBV 227:229 HBV 227:229 The envelope proteins of hepatitis B virus (HBV) bear an N-linked glycosylation site at N146 within the immunodominant a-determinant in the antigenic loop (AGL) region. 24899172 1 19 theme hepatitis 208:216 arg1 virus 220:224 hepatitis B virus 208:224 hepatitis B virus (HBV) 208:230 The envelope proteins of hepatitis B virus (HBV) bear an N-linked glycosylation site at N146 within the immunodominant a-determinant in the antigenic loop (AGL) region. 24899172 9 20 theme neutralizing 1892:1903 arg1 antibodies 1905:1914 neutralizing antibodies 1892:1914 neutralizing antibodies 1892:1914 Taken together, these findings suggest that the nonglycosylated N146 is essential for infectivity, while the glycosylated form, in addition to its importance for HBV virion secretion, is instrumental in shielding the a-determinant from neutralizing antibodies. 24899172 12 21 from surface 2284:2290 arg1 coexistence 2224:2234 the coexistence 2220:2234 the coexistence of nonglycosylated and glycosylated N146 at the surface of HBV 2220:2297 Our data suggest that the coexistence of nonglycosylated and glycosylated N146 at the surface of HBV reflects the dual function of this determinant in infectivity and immune escape. 24899172 1 22 theme virus 220:224 arg1 proteins 196:203 The envelope proteins 183:203 The envelope proteins of hepatitis B virus (HBV) 183:230 The envelope proteins of hepatitis B virus (HBV) bear an N-linked glycosylation site at N146 within the immunodominant a-determinant in the antigenic loop (AGL) region. 24899172 0 23 theme susceptibility 140:153 arg1 secretion 93:101 secretion 93:101 secretion of viral particles, infectivity, and susceptibility to neutralizing antibodies 93:180 Modification of the hepatitis B virus envelope protein glycosylation pattern interferes with secretion of viral particles, infectivity, and susceptibility to neutralizing antibodies. 24899172 4 24 theme N146 714:717 arg1 site 733:736 the N146 glycosylation site 710:736 the N146 glycosylation site 710:736 We observed that the removal of the N146 glycosylation site by mutagenesis was permissive to envelope protein synthesis and stability and to secretion of subviral particles (SVPs) and hepatitis delta virus (HDV) virions, but it was detrimental to HBV virion production. 24899172 0 25 theme neutralizing 158:169 arg1 antibodies 171:180 neutralizing antibodies 158:180 neutralizing antibodies 158:180 Modification of the hepatitis B virus envelope protein glycosylation pattern interferes with secretion of viral particles, infectivity, and susceptibility to neutralizing antibodies. 24899172 12 26 gly nonglycosylated 2239:2253 arg1 N146 2272:2275 nonglycosylated and glycosylated N146 2239:2275 nonglycosylated and glycosylated N146 2239:2275 Our data suggest that the coexistence of nonglycosylated and glycosylated N146 at the surface of HBV reflects the dual function of this determinant in infectivity and immune escape. 24899172 12 27 theme N146 2272:2275 arg1 coexistence 2224:2234 the coexistence 2220:2234 the coexistence of nonglycosylated and glycosylated N146 at the surface of HBV 2220:2297 Our data suggest that the coexistence of nonglycosylated and glycosylated N146 at the surface of HBV reflects the dual function of this determinant in infectivity and immune escape. 24899172 10 28 theme particles 1951:1959 arg1 surface 1936:1942 the surface 1932:1942 the surface of HBV particles 1932:1959 IMPORTANCE: At the surface of HBV particles, the immunodominant a-determinant is the main target of neutralizing antibodies and an essential determinant of infectivity. 24899172 8 29 gly N-glycosylation 1391:1405 arg2 sites 1407:1411 Infectivity-compatible N-glycosylation sites 1368:1411 Infectivity-compatible N-glycosylation sites 1368:1411 Infectivity-compatible N-glycosylation sites could be inserted at 3 positions (positions 115, 129, and 136), but when all three positions were glycosylated, the hyperglycosylated mutant was substantially attenuated at viral entry, while it acquired resistance to neutralizing antibodies. 24899172 1 30 theme antigenic 323:331 arg1 region 344:349 the antigenic loop (AGL) region 319:349 the antigenic loop (AGL) region 319:349 The envelope proteins of hepatitis B virus (HBV) bear an N-linked glycosylation site at N146 within the immunodominant a-determinant in the antigenic loop (AGL) region. 24899172 9 31 theme nonglycosylated 1704:1718 arg1 essential 1728:1736 essential 1728:1736 essential 1728:1736 Taken together, these findings suggest that the nonglycosylated N146 is essential for infectivity, while the glycosylated form, in addition to its importance for HBV virion secretion, is instrumental in shielding the a-determinant from neutralizing antibodies. 24899172 9 31 theme nonglycosylated 1704:1718 arg1 N146 1720:1723 the nonglycosylated N146 1700:1723 the nonglycosylated N146 1700:1723 Taken together, these findings suggest that the nonglycosylated N146 is essential for infectivity, while the glycosylated form, in addition to its importance for HBV virion secretion, is instrumental in shielding the a-determinant from neutralizing antibodies. 24899172 13 32 theme HBV 2409:2411 arg1 pattern 2427:2433 the HBV glycosylation pattern 2405:2433 the HBV glycosylation pattern 2405:2433 Hence, a modification of the HBV glycosylation pattern affects not only virion assembly and infectivity but also immune escape. 24899172 9 33 dep importance 1803:1812 arg1 addition 1787:1794 addition 1787:1794 addition 1787:1794 Taken together, these findings suggest that the nonglycosylated N146 is essential for infectivity, while the glycosylated form, in addition to its importance for HBV virion secretion, is instrumental in shielding the a-determinant from neutralizing antibodies. 24899172 13 34 theme immune 2493:2498 arg1 escape 2500:2505 immune escape 2493:2505 not only virion assembly and infectivity but also immune escape 2443:2505 Hence, a modification of the HBV glycosylation pattern affects not only virion assembly and infectivity but also immune escape. 24899172 11 35 theme proteins 2188:2195 arg1 half 2167:2170 only half 2162:2170 only half of the envelope proteins 2162:2195 It contains an N-glycosylation site at position 146, which is functional on only half of the envelope proteins. 24899172 9 36 gly glycosylated 1765:1776 arg1 instrumental 1843:1854 instrumental 1843:1854 instrumental 1843:1854 Taken together, these findings suggest that the nonglycosylated N146 is essential for infectivity, while the glycosylated form, in addition to its importance for HBV virion secretion, is instrumental in shielding the a-determinant from neutralizing antibodies. 24899172 9 36 gly glycosylated 1765:1776 arg1 form 1778:1781 the glycosylated form 1761:1781 the glycosylated form 1761:1781 Taken together, these findings suggest that the nonglycosylated N146 is essential for infectivity, while the glycosylated form, in addition to its importance for HBV virion secretion, is instrumental in shielding the a-determinant from neutralizing antibodies. 24899172 11 37 gly N-glycosylation 2101:2115 arg2 functional 2148:2157 functional 2148:2157 functional 2148:2157 It contains an N-glycosylation site at position 146, which is functional on only half of the envelope proteins. 24899172 11 37 gly N-glycosylation 2101:2115 arg2 site 2117:2120 an N-glycosylation site 2098:2120 an N-glycosylation site 2098:2120 It contains an N-glycosylation site at position 146, which is functional on only half of the envelope proteins. 24899172 11 37 gly N-glycosylation 2101:2115 arg2 position 2125:2132 position 146 2125:2136 position 146 2125:2136 It contains an N-glycosylation site at position 146, which is functional on only half of the envelope proteins. 24899172 4 38 theme HBV 925:927 arg1 production 936:945 HBV virion production 925:945 HBV virion production 925:945 We observed that the removal of the N146 glycosylation site by mutagenesis was permissive to envelope protein synthesis and stability and to secretion of subviral particles (SVPs) and hepatitis delta virus (HDV) virions, but it was detrimental to HBV virion production. 24899172 2 39 from ratio 427:431 arg1 envelope 487:494 the viral envelope 477:494 the viral envelope 477:494 This glycosylation site is never fully functional, leading to a nearly 1/1 ratio of glycosylated/nonglycosylated isoforms in the viral envelope. 24899172 4 40 theme envelope 771:778 arg1 synthesis 788:796 envelope protein synthesis 771:796 envelope protein synthesis 771:796 We observed that the removal of the N146 glycosylation site by mutagenesis was permissive to envelope protein synthesis and stability and to secretion of subviral particles (SVPs) and hepatitis delta virus (HDV) virions, but it was detrimental to HBV virion production. 24899172 0 41 theme viral 106:110 arg1 particles 112:120 viral particles 106:120 viral particles 106:120 Modification of the hepatitis B virus envelope protein glycosylation pattern interferes with secretion of viral particles, infectivity, and susceptibility to neutralizing antibodies. 24899172 5 42 theme Several 948:954 arg1 positions 956:964 Several positions 948:964 Several positions in the AGL 948:975 Several positions in the AGL could substitute for position 146 as the glycosylation acceptor site. 24899172 2 43 theme 1/1 423:425 arg1 ratio 427:431 a nearly 1/1 ratio 414:431 a nearly 1/1 ratio of glycosylated/nonglycosylated isoforms in the viral envelope 414:494 This glycosylation site is never fully functional, leading to a nearly 1/1 ratio of glycosylated/nonglycosylated isoforms in the viral envelope. 24899172 2 44 gly glycosylation 357:369 arg2 site 371:374 This glycosylation site 352:374 This glycosylation site 352:374 This glycosylation site is never fully functional, leading to a nearly 1/1 ratio of glycosylated/nonglycosylated isoforms in the viral envelope. 24899172 4 45 theme site 733:736 arg1 permissive 757:766 permissive 757:766 permissive 757:766 We observed that the removal of the N146 glycosylation site by mutagenesis was permissive to envelope protein synthesis and stability and to secretion of subviral particles (SVPs) and hepatitis delta virus (HDV) virions, but it was detrimental to HBV virion production. 24899172 4 45 theme site 733:736 arg1 removal 699:705 the removal 695:705 the removal of the N146 glycosylation site by mutagenesis 695:751 We observed that the removal of the N146 glycosylation site by mutagenesis was permissive to envelope protein synthesis and stability and to secretion of subviral particles (SVPs) and hepatitis delta virus (HDV) virions, but it was detrimental to HBV virion production. 24899172 10 46 from surface 1936:1942 arg1 IMPORTANCE 1917:1926 IMPORTANCE 1917:1926 IMPORTANCE 1917:1926 IMPORTANCE: At the surface of HBV particles, the immunodominant a-determinant is the main target of neutralizing antibodies and an essential determinant of infectivity. 24899172 10 46 from surface 1936:1942 arg1 a-determinant 1981:1993 the immunodominant a-determinant 1962:1993 the immunodominant a-determinant 1962:1993 IMPORTANCE: At the surface of HBV particles, the immunodominant a-determinant is the main target of neutralizing antibodies and an essential determinant of infectivity. 24899172 10 46 from surface 1936:1942 arg1 determinant 2058:2068 an essential determinant 2045:2068 an essential determinant of infectivity 2045:2083 IMPORTANCE: At the surface of HBV particles, the immunodominant a-determinant is the main target of neutralizing antibodies and an essential determinant of infectivity. 24899172 10 46 from surface 1936:1942 arg1 target 2007:2012 the main target 1998:2012 the main target of neutralizing antibodies 1998:2039 IMPORTANCE: At the surface of HBV particles, the immunodominant a-determinant is the main target of neutralizing antibodies and an essential determinant of infectivity. 24899172 2 47 theme isoforms 465:472 arg1 ratio 427:431 a nearly 1/1 ratio 414:431 a nearly 1/1 ratio of glycosylated/nonglycosylated isoforms in the viral envelope 414:494 This glycosylation site is never fully functional, leading to a nearly 1/1 ratio of glycosylated/nonglycosylated isoforms in the viral envelope. 24899172 0 48 theme glycosylation 55:67 arg1 pattern 69:75 the hepatitis B virus envelope protein glycosylation pattern 16:75 the hepatitis B virus envelope protein glycosylation pattern 16:75 Modification of the hepatitis B virus envelope protein glycosylation pattern interferes with secretion of viral particles, infectivity, and susceptibility to neutralizing antibodies. 24899172 3 49 theme glycosylated 635:646 arg1 isoforms 668:675 the glycosylated and nonglycosylated isoforms 631:675 the glycosylated and nonglycosylated isoforms 631:675 Here we investigated the requirement for a precise positioning of N-linked glycan at amino acid 146 and the functions associated with the glycosylated and nonglycosylated isoforms. 24899172 3 50 from acid 588:591 arg1 requirement 522:532 the requirement 518:532 the requirement for a precise positioning of N-linked glycan at amino acid 146 518:595 Here we investigated the requirement for a precise positioning of N-linked glycan at amino acid 146 and the functions associated with the glycosylated and nonglycosylated isoforms. 24899172 3 50 from acid 588:591 arg1 functions 605:613 the functions 601:613 the functions associated with the glycosylated and nonglycosylated isoforms 601:675 Here we investigated the requirement for a precise positioning of N-linked glycan at amino acid 146 and the functions associated with the glycosylated and nonglycosylated isoforms. 24899172 0 51 theme B 30:30 arg1 virus 32:36 hepatitis B virus 20:36 the hepatitis B virus envelope protein glycosylation pattern 16:75 Modification of the hepatitis B virus envelope protein glycosylation pattern interferes with secretion of viral particles, infectivity, and susceptibility to neutralizing antibodies. 24899172 1 52 theme immunodominant 287:300 arg1 a-determinant 302:314 the immunodominant a-determinant 283:314 the immunodominant a-determinant in the antigenic loop (AGL) region 283:349 The envelope proteins of hepatitis B virus (HBV) bear an N-linked glycosylation site at N146 within the immunodominant a-determinant in the antigenic loop (AGL) region. 24899172 8 53 gly hyperglycosylated 1529:1545 arg1 mutant 1547:1552 the hyperglycosylated mutant 1525:1552 the hyperglycosylated mutant 1525:1552 Infectivity-compatible N-glycosylation sites could be inserted at 3 positions (positions 115, 129, and 136), but when all three positions were glycosylated, the hyperglycosylated mutant was substantially attenuated at viral entry, while it acquired resistance to neutralizing antibodies. 24899172 4 54 theme virion 929:934 arg1 production 936:945 HBV virion production 925:945 HBV virion production 925:945 We observed that the removal of the N146 glycosylation site by mutagenesis was permissive to envelope protein synthesis and stability and to secretion of subviral particles (SVPs) and hepatitis delta virus (HDV) virions, but it was detrimental to HBV virion production. 24899172 0 55 theme envelope 38:45 arg1 pattern 69:75 the hepatitis B virus envelope protein glycosylation pattern 16:75 the hepatitis B virus envelope protein glycosylation pattern 16:75 Modification of the hepatitis B virus envelope protein glycosylation pattern interferes with secretion of viral particles, infectivity, and susceptibility to neutralizing antibodies. 24899172 7 56 gly glycosylation 1223:1235 arg2 sites 1237:1241 5 AGL glycosylation sites 1217:1241 5 AGL glycosylation sites 1217:1241 Envelope proteins bearing 5 AGL glycosylation sites became hyperglycosylated, leading to an increased capacity for SVP secretion at the expense of HBV and HDV virion secretion. 24899172 7 56 gly glycosylation 1223:1235 arg2 5 1217:1217 5 1217:1217 5 1217:1217 Envelope proteins bearing 5 AGL glycosylation sites became hyperglycosylated, leading to an increased capacity for SVP secretion at the expense of HBV and HDV virion secretion. 24899172 11 57 theme N-glycosylation 2101:2115 arg1 site 2117:2120 an N-glycosylation site 2098:2120 an N-glycosylation site 2098:2120 It contains an N-glycosylation site at position 146, which is functional on only half of the envelope proteins. 24899172 11 57 theme N-glycosylation 2101:2115 arg1 functional 2148:2157 functional 2148:2157 functional 2148:2157 It contains an N-glycosylation site at position 146, which is functional on only half of the envelope proteins. 24899172 10 58 theme neutralizing 2017:2028 arg1 antibodies 2030:2039 neutralizing antibodies 2017:2039 neutralizing antibodies 2017:2039 IMPORTANCE: At the surface of HBV particles, the immunodominant a-determinant is the main target of neutralizing antibodies and an essential determinant of infectivity. 24899172 12 59 theme immune 2365:2370 arg1 escape 2372:2377 immune escape 2365:2377 immune escape 2365:2377 Our data suggest that the coexistence of nonglycosylated and glycosylated N146 at the surface of HBV reflects the dual function of this determinant in infectivity and immune escape. 24899172 8 60 theme Infectivity-compatible 1368:1389 arg1 sites 1407:1411 Infectivity-compatible N-glycosylation sites 1368:1411 Infectivity-compatible N-glycosylation sites 1368:1411 Infectivity-compatible N-glycosylation sites could be inserted at 3 positions (positions 115, 129, and 136), but when all three positions were glycosylated, the hyperglycosylated mutant was substantially attenuated at viral entry, while it acquired resistance to neutralizing antibodies. 24899172 7 61 theme AGL 1219:1221 arg1 sites 1237:1241 5 AGL glycosylation sites 1217:1241 5 AGL glycosylation sites 1217:1241 Envelope proteins bearing 5 AGL glycosylation sites became hyperglycosylated, leading to an increased capacity for SVP secretion at the expense of HBV and HDV virion secretion. 24899172 3 62 theme nonglycosylated 652:666 arg1 isoforms 668:675 the glycosylated and nonglycosylated isoforms 631:675 the glycosylated and nonglycosylated isoforms 631:675 Here we investigated the requirement for a precise positioning of N-linked glycan at amino acid 146 and the functions associated with the glycosylated and nonglycosylated isoforms. 24899172 13 63 theme glycosylation 2413:2425 arg1 pattern 2427:2433 the HBV glycosylation pattern 2405:2433 the HBV glycosylation pattern 2405:2433 Hence, a modification of the HBV glycosylation pattern affects not only virion assembly and infectivity but also immune escape. 24899172 9 64 theme HBV 1818:1820 arg1 secretion 1829:1837 HBV virion secretion 1818:1837 HBV virion secretion 1818:1837 Taken together, these findings suggest that the nonglycosylated N146 is essential for infectivity, while the glycosylated form, in addition to its importance for HBV virion secretion, is instrumental in shielding the a-determinant from neutralizing antibodies. 24899172 1 65 contain bear 232:235 arg2 site 263:266 an N-linked glycosylation site 237:266 an N-linked glycosylation site at N146 within the immunodominant a-determinant in the antigenic loop (AGL) region 237:349 The envelope proteins of hepatitis B virus (HBV) bear an N-linked glycosylation site at N146 within the immunodominant a-determinant in the antigenic loop (AGL) region. 24899172 1 65 contain bear 232:235 arg1 proteins 196:203 The envelope proteins 183:203 The envelope proteins of hepatitis B virus (HBV) 183:230 The envelope proteins of hepatitis B virus (HBV) bear an N-linked glycosylation site at N146 within the immunodominant a-determinant in the antigenic loop (AGL) region. 24899172 12 66 theme determinant 2334:2344 arg1 function 2317:2324 the dual function 2308:2324 the dual function of this determinant in infectivity and immune escape 2308:2377 Our data suggest that the coexistence of nonglycosylated and glycosylated N146 at the surface of HBV reflects the dual function of this determinant in infectivity and immune escape. 24899172 7 67 theme Envelope 1191:1198 arg1 proteins 1200:1207 Envelope proteins 1191:1207 Envelope proteins bearing 5 AGL glycosylation sites 1191:1241 Envelope proteins bearing 5 AGL glycosylation sites became hyperglycosylated, leading to an increased capacity for SVP secretion at the expense of HBV and HDV virion secretion. 24899172 5 68 gly glycosylation 1018:1030 arg2 site 1041:1044 the glycosylation acceptor site 1014:1044 the glycosylation acceptor site 1014:1044 Several positions in the AGL could substitute for position 146 as the glycosylation acceptor site. 24899172 1 69 theme glycosylation 249:261 arg1 site 263:266 an N-linked glycosylation site 237:266 an N-linked glycosylation site at N146 within the immunodominant a-determinant in the antigenic loop (AGL) region 237:349 The envelope proteins of hepatitis B virus (HBV) bear an N-linked glycosylation site at N146 within the immunodominant a-determinant in the antigenic loop (AGL) region. 24899172 4 70 theme hepatitis 862:870 arg1 HDV 885:887 HDV 885:887 HDV 885:887 We observed that the removal of the N146 glycosylation site by mutagenesis was permissive to envelope protein synthesis and stability and to secretion of subviral particles (SVPs) and hepatitis delta virus (HDV) virions, but it was detrimental to HBV virion production. 24899172 4 70 theme hepatitis 862:870 arg1 virus 878:882 hepatitis delta virus 862:882 hepatitis delta virus (HDV) virions 862:896 We observed that the removal of the N146 glycosylation site by mutagenesis was permissive to envelope protein synthesis and stability and to secretion of subviral particles (SVPs) and hepatitis delta virus (HDV) virions, but it was detrimental to HBV virion production. 24899172 12 71 theme dual 2312:2315 arg1 function 2317:2324 the dual function 2308:2324 the dual function of this determinant in infectivity and immune escape 2308:2377 Our data suggest that the coexistence of nonglycosylated and glycosylated N146 at the surface of HBV reflects the dual function of this determinant in infectivity and immune escape. 24899172 12 72 from function 2317:2324 arg1 infectivity 2349:2359 infectivity 2349:2359 infectivity 2349:2359 Our data suggest that the coexistence of nonglycosylated and glycosylated N146 at the surface of HBV reflects the dual function of this determinant in infectivity and immune escape. 24899172 12 72 from function 2317:2324 arg1 escape 2372:2377 immune escape 2365:2377 immune escape 2365:2377 Our data suggest that the coexistence of nonglycosylated and glycosylated N146 at the surface of HBV reflects the dual function of this determinant in infectivity and immune escape. 24899172 1 73 link N-linked 240:247 arg1 site 263:266 an N-linked glycosylation site 237:266 an N-linked glycosylation site at N146 within the immunodominant a-determinant in the antigenic loop (AGL) region 237:349 The envelope proteins of hepatitis B virus (HBV) bear an N-linked glycosylation site at N146 within the immunodominant a-determinant in the antigenic loop (AGL) region. 24899172 4 74 theme subviral 832:839 arg1 SVPs 852:855 SVPs 852:855 SVPs 852:855 We observed that the removal of the N146 glycosylation site by mutagenesis was permissive to envelope protein synthesis and stability and to secretion of subviral particles (SVPs) and hepatitis delta virus (HDV) virions, but it was detrimental to HBV virion production. 24899172 4 74 theme subviral 832:839 arg1 particles 841:849 subviral particles 832:849 subviral particles (SVPs) 832:856 We observed that the removal of the N146 glycosylation site by mutagenesis was permissive to envelope protein synthesis and stability and to secretion of subviral particles (SVPs) and hepatitis delta virus (HDV) virions, but it was detrimental to HBV virion production. 24899172 11 75 theme only 2162:2165 arg1 half 2167:2170 only half 2162:2170 only half of the envelope proteins 2162:2195 It contains an N-glycosylation site at position 146, which is functional on only half of the envelope proteins. 24899172 1 76 theme envelope 187:194 arg1 proteins 196:203 The envelope proteins 183:203 The envelope proteins of hepatitis B virus (HBV) 183:230 The envelope proteins of hepatitis B virus (HBV) bear an N-linked glycosylation site at N146 within the immunodominant a-determinant in the antigenic loop (AGL) region. 24899172 7 77 theme secretion 1357:1365 arg1 expense 1327:1333 the expense 1323:1333 the expense of HBV and HDV virion secretion 1323:1365 Envelope proteins bearing 5 AGL glycosylation sites became hyperglycosylated, leading to an increased capacity for SVP secretion at the expense of HBV and HDV virion secretion. 24899172 0 78 theme infectivity 123:133 arg1 secretion 93:101 secretion 93:101 secretion of viral particles, infectivity, and susceptibility to neutralizing antibodies 93:180 Modification of the hepatitis B virus envelope protein glycosylation pattern interferes with secretion of viral particles, infectivity, and susceptibility to neutralizing antibodies. 24899172 3 79 theme precise 540:546 arg1 positioning 548:558 a precise positioning 538:558 a precise positioning of N-linked glycan 538:577 Here we investigated the requirement for a precise positioning of N-linked glycan at amino acid 146 and the functions associated with the glycosylated and nonglycosylated isoforms. 24899172 4 80 theme virions 890:896 arg1 secretion 819:827 secretion 819:827 secretion of subviral particles (SVPs) and hepatitis delta virus (HDV) virions 819:896 We observed that the removal of the N146 glycosylation site by mutagenesis was permissive to envelope protein synthesis and stability and to secretion of subviral particles (SVPs) and hepatitis delta virus (HDV) virions, but it was detrimental to HBV virion production. 24899172 7 81 theme HDV 1346:1348 arg1 secretion 1357:1365 HDV virion secretion 1346:1365 HDV virion secretion 1346:1365 Envelope proteins bearing 5 AGL glycosylation sites became hyperglycosylated, leading to an increased capacity for SVP secretion at the expense of HBV and HDV virion secretion. 24899172 3 82 theme amino 582:586 arg1 acid 588:591 amino acid 146 582:595 amino acid 146 582:595 Here we investigated the requirement for a precise positioning of N-linked glycan at amino acid 146 and the functions associated with the glycosylated and nonglycosylated isoforms. 24899172 1 83 theme B 218:218 arg1 HBV 227:229 HBV 227:229 HBV 227:229 The envelope proteins of hepatitis B virus (HBV) bear an N-linked glycosylation site at N146 within the immunodominant a-determinant in the antigenic loop (AGL) region. 24899172 1 83 theme B 218:218 arg1 virus 220:224 hepatitis B virus 208:224 hepatitis B virus (HBV) 208:230 The envelope proteins of hepatitis B virus (HBV) bear an N-linked glycosylation site at N146 within the immunodominant a-determinant in the antigenic loop (AGL) region. 24899172 12 84 theme HBV 2295:2297 arg1 surface 2284:2290 the surface 2280:2290 the surface of HBV 2280:2297 Our data suggest that the coexistence of nonglycosylated and glycosylated N146 at the surface of HBV reflects the dual function of this determinant in infectivity and immune escape. 24899172 6 85 theme polar 1176:1180 arg1 residue 1182:1188 a polar residue 1174:1188 a polar residue 1174:1188 At position 146, neither a glycan chain nor asparagine was absolutely required for infectivity, but there was a preference for a polar residue. 24899172 3 86 theme glycan 572:577 arg1 positioning 548:558 a precise positioning 538:558 a precise positioning of N-linked glycan 538:577 Here we investigated the requirement for a precise positioning of N-linked glycan at amino acid 146 and the functions associated with the glycosylated and nonglycosylated isoforms. 24899172 4 87 theme virus 878:882 arg1 virions 890:896 hepatitis delta virus (HDV) virions 862:896 hepatitis delta virus (HDV) virions 862:896 We observed that the removal of the N146 glycosylation site by mutagenesis was permissive to envelope protein synthesis and stability and to secretion of subviral particles (SVPs) and hepatitis delta virus (HDV) virions, but it was detrimental to HBV virion production. 24899172 12 88 theme glycosylated 2259:2270 arg1 N146 2272:2275 nonglycosylated and glycosylated N146 2239:2275 nonglycosylated and glycosylated N146 2239:2275 Our data suggest that the coexistence of nonglycosylated and glycosylated N146 at the surface of HBV reflects the dual function of this determinant in infectivity and immune escape. 24899172 9 89 gly nonglycosylated 1704:1718 arg1 essential 1728:1736 essential 1728:1736 essential 1728:1736 Taken together, these findings suggest that the nonglycosylated N146 is essential for infectivity, while the glycosylated form, in addition to its importance for HBV virion secretion, is instrumental in shielding the a-determinant from neutralizing antibodies. 24899172 9 89 gly nonglycosylated 1704:1718 arg1 N146 1720:1723 the nonglycosylated N146 1700:1723 the nonglycosylated N146 1700:1723 Taken together, these findings suggest that the nonglycosylated N146 is essential for infectivity, while the glycosylated form, in addition to its importance for HBV virion secretion, is instrumental in shielding the a-determinant from neutralizing antibodies. 24899172 0 90 theme pattern 69:75 arg1 Modification 0:11 Modification 0:11 Modification of the hepatitis B virus envelope protein glycosylation pattern 0:75 Modification of the hepatitis B virus envelope protein glycosylation pattern interferes with secretion of viral particles, infectivity, and susceptibility to neutralizing antibodies. 24899172 5 91 theme glycosylation 1018:1030 arg1 site 1041:1044 the glycosylation acceptor site 1014:1044 the glycosylation acceptor site 1014:1044 Several positions in the AGL could substitute for position 146 as the glycosylation acceptor site. 24899172 2 92 theme viral 481:485 arg1 envelope 487:494 the viral envelope 477:494 the viral envelope 477:494 This glycosylation site is never fully functional, leading to a nearly 1/1 ratio of glycosylated/nonglycosylated isoforms in the viral envelope. 24899172 7 93 theme SVP 1306:1308 arg1 secretion 1310:1318 SVP secretion 1306:1318 SVP secretion at the expense of HBV and HDV virion secretion 1306:1365 Envelope proteins bearing 5 AGL glycosylation sites became hyperglycosylated, leading to an increased capacity for SVP secretion at the expense of HBV and HDV virion secretion. 24899172 10 94 theme HBV 1947:1949 arg1 particles 1951:1959 HBV particles 1947:1959 HBV particles 1947:1959 IMPORTANCE: At the surface of HBV particles, the immunodominant a-determinant is the main target of neutralizing antibodies and an essential determinant of infectivity. 24899172 1 95 theme loop 333:336 arg1 region 344:349 the antigenic loop (AGL) region 319:349 the antigenic loop (AGL) region 319:349 The envelope proteins of hepatitis B virus (HBV) bear an N-linked glycosylation site at N146 within the immunodominant a-determinant in the antigenic loop (AGL) region. 24899172 3 96 link N-linked 563:570 arg1 glycan 572:577 N-linked glycan 563:577 N-linked glycan 563:577 Here we investigated the requirement for a precise positioning of N-linked glycan at amino acid 146 and the functions associated with the glycosylated and nonglycosylated isoforms. 24899172 12 97 theme nonglycosylated 2239:2253 arg1 N146 2272:2275 nonglycosylated and glycosylated N146 2239:2275 nonglycosylated and glycosylated N146 2239:2275 Our data suggest that the coexistence of nonglycosylated and glycosylated N146 at the surface of HBV reflects the dual function of this determinant in infectivity and immune escape. 24899172 4 98 gly glycosylation 719:731 arg2 site 733:736 the N146 glycosylation site 710:736 the N146 glycosylation site 710:736 We observed that the removal of the N146 glycosylation site by mutagenesis was permissive to envelope protein synthesis and stability and to secretion of subviral particles (SVPs) and hepatitis delta virus (HDV) virions, but it was detrimental to HBV virion production. 24899172 1 99 theme AGL 339:341 arg1 region 344:349 the antigenic loop (AGL) region 319:349 the antigenic loop (AGL) region 319:349 The envelope proteins of hepatitis B virus (HBV) bear an N-linked glycosylation site at N146 within the immunodominant a-determinant in the antigenic loop (AGL) region. 24899172 10 100 theme immunodominant 1966:1979 arg1 IMPORTANCE 1917:1926 IMPORTANCE 1917:1926 IMPORTANCE 1917:1926 IMPORTANCE: At the surface of HBV particles, the immunodominant a-determinant is the main target of neutralizing antibodies and an essential determinant of infectivity. 24899172 10 100 theme immunodominant 1966:1979 arg1 a-determinant 1981:1993 the immunodominant a-determinant 1962:1993 the immunodominant a-determinant 1962:1993 IMPORTANCE: At the surface of HBV particles, the immunodominant a-determinant is the main target of neutralizing antibodies and an essential determinant of infectivity. 24899172 10 100 theme immunodominant 1966:1979 arg1 target 2007:2012 the main target 1998:2012 the main target of neutralizing antibodies 1998:2039 IMPORTANCE: At the surface of HBV particles, the immunodominant a-determinant is the main target of neutralizing antibodies and an essential determinant of infectivity. 24899172 0 101 theme particles 112:120 arg1 secretion 93:101 secretion 93:101 secretion of viral particles, infectivity, and susceptibility to neutralizing antibodies 93:180 Modification of the hepatitis B virus envelope protein glycosylation pattern interferes with secretion of viral particles, infectivity, and susceptibility to neutralizing antibodies. 24899172 12 102 gly glycosylated 2259:2270 arg1 N146 2272:2275 nonglycosylated and glycosylated N146 2239:2275 nonglycosylated and glycosylated N146 2239:2275 Our data suggest that the coexistence of nonglycosylated and glycosylated N146 at the surface of HBV reflects the dual function of this determinant in infectivity and immune escape. 24899172 7 103 theme increased 1283:1291 arg1 capacity 1293:1300 an increased capacity 1280:1300 an increased capacity for SVP secretion at the expense of HBV and HDV virion secretion 1280:1365 Envelope proteins bearing 5 AGL glycosylation sites became hyperglycosylated, leading to an increased capacity for SVP secretion at the expense of HBV and HDV virion secretion. 24899172 11 104 theme envelope 2179:2186 arg1 proteins 2188:2195 the envelope proteins 2175:2195 the envelope proteins 2175:2195 It contains an N-glycosylation site at position 146, which is functional on only half of the envelope proteins. 24899172 4 105 theme glycosylation 719:731 arg1 site 733:736 the N146 glycosylation site 710:736 the N146 glycosylation site 710:736 We observed that the removal of the N146 glycosylation site by mutagenesis was permissive to envelope protein synthesis and stability and to secretion of subviral particles (SVPs) and hepatitis delta virus (HDV) virions, but it was detrimental to HBV virion production. 24899172 2 106 theme glycosylation 357:369 arg1 site 371:374 This glycosylation site 352:374 This glycosylation site 352:374 This glycosylation site is never fully functional, leading to a nearly 1/1 ratio of glycosylated/nonglycosylated isoforms in the viral envelope. 24899172 0 107 theme hepatitis 20:28 arg1 virus 32:36 hepatitis B virus 20:36 the hepatitis B virus envelope protein glycosylation pattern 16:75 Modification of the hepatitis B virus envelope protein glycosylation pattern interferes with secretion of viral particles, infectivity, and susceptibility to neutralizing antibodies. 24899172 1 108 gly glycosylation 249:261 arg2 site 263:266 an N-linked glycosylation site 237:266 an N-linked glycosylation site at N146 within the immunodominant a-determinant in the antigenic loop (AGL) region 237:349 The envelope proteins of hepatitis B virus (HBV) bear an N-linked glycosylation site at N146 within the immunodominant a-determinant in the antigenic loop (AGL) region. 24899172 1 108 gly glycosylation 249:261 arg2 N146 271:274 N146 271:274 N146 271:274 The envelope proteins of hepatitis B virus (HBV) bear an N-linked glycosylation site at N146 within the immunodominant a-determinant in the antigenic loop (AGL) region. 24899172 8 109 gly glycosylated 1511:1522 arg1 positions 1496:1504 all three positions 1486:1504 all three positions 1486:1504 Infectivity-compatible N-glycosylation sites could be inserted at 3 positions (positions 115, 129, and 136), but when all three positions were glycosylated, the hyperglycosylated mutant was substantially attenuated at viral entry, while it acquired resistance to neutralizing antibodies. 24899172 7 110 from expense 1327:1333 arg1 secretion 1310:1318 SVP secretion 1306:1318 SVP secretion at the expense of HBV and HDV virion secretion 1306:1365 Envelope proteins bearing 5 AGL glycosylation sites became hyperglycosylated, leading to an increased capacity for SVP secretion at the expense of HBV and HDV virion secretion. 24899172 9 111 theme glycosylated 1765:1776 arg1 instrumental 1843:1854 instrumental 1843:1854 instrumental 1843:1854 Taken together, these findings suggest that the nonglycosylated N146 is essential for infectivity, while the glycosylated form, in addition to its importance for HBV virion secretion, is instrumental in shielding the a-determinant from neutralizing antibodies. 24899172 9 111 theme glycosylated 1765:1776 arg1 form 1778:1781 the glycosylated form 1761:1781 the glycosylated form 1761:1781 Taken together, these findings suggest that the nonglycosylated N146 is essential for infectivity, while the glycosylated form, in addition to its importance for HBV virion secretion, is instrumental in shielding the a-determinant from neutralizing antibodies. 24899172 0 112 theme virus 32:36 arg1 pattern 69:75 the hepatitis B virus envelope protein glycosylation pattern 16:75 the hepatitis B virus envelope protein glycosylation pattern 16:75 Modification of the hepatitis B virus envelope protein glycosylation pattern interferes with secretion of viral particles, infectivity, and susceptibility to neutralizing antibodies. 24899172 2 113 gly glycosylated/nonglycosylated 436:463 arg1 isoforms 465:472 glycosylated/nonglycosylated isoforms 436:472 glycosylated/nonglycosylated isoforms 436:472 This glycosylation site is never fully functional, leading to a nearly 1/1 ratio of glycosylated/nonglycosylated isoforms in the viral envelope. 24899172 9 114 from antibodies 1905:1914 arg1 a-determinant 1873:1885 the a-determinant 1869:1885 the a-determinant from neutralizing antibodies 1869:1914 Taken together, these findings suggest that the nonglycosylated N146 is essential for infectivity, while the glycosylated form, in addition to its importance for HBV virion secretion, is instrumental in shielding the a-determinant from neutralizing antibodies. 24899172 2 115 theme glycosylated/nonglycosylated 436:463 arg1 isoforms 465:472 glycosylated/nonglycosylated isoforms 436:472 glycosylated/nonglycosylated isoforms 436:472 This glycosylation site is never fully functional, leading to a nearly 1/1 ratio of glycosylated/nonglycosylated isoforms in the viral envelope. 24899172 0 116 theme protein 47:53 arg1 pattern 69:75 the hepatitis B virus envelope protein glycosylation pattern 16:75 the hepatitis B virus envelope protein glycosylation pattern 16:75 Modification of the hepatitis B virus envelope protein glycosylation pattern interferes with secretion of viral particles, infectivity, and susceptibility to neutralizing antibodies. 24899172 7 117 theme glycosylation 1223:1235 arg1 sites 1237:1241 5 AGL glycosylation sites 1217:1241 5 AGL glycosylation sites 1217:1241 Envelope proteins bearing 5 AGL glycosylation sites became hyperglycosylated, leading to an increased capacity for SVP secretion at the expense of HBV and HDV virion secretion. 24899172 7 118 theme HBV 1338:1340 arg1 expense 1327:1333 the expense 1323:1333 the expense of HBV and HDV virion secretion 1323:1365 Envelope proteins bearing 5 AGL glycosylation sites became hyperglycosylated, leading to an increased capacity for SVP secretion at the expense of HBV and HDV virion secretion. 24899172 6 119 theme glycan 1074:1079 arg1 chain 1081:1085 a glycan chain 1072:1085 a glycan chain 1072:1085 At position 146, neither a glycan chain nor asparagine was absolutely required for infectivity, but there was a preference for a polar residue. 24899172 8 120 theme hyperglycosylated 1529:1545 arg1 mutant 1547:1552 the hyperglycosylated mutant 1525:1552 the hyperglycosylated mutant 1525:1552 Infectivity-compatible N-glycosylation sites could be inserted at 3 positions (positions 115, 129, and 136), but when all three positions were glycosylated, the hyperglycosylated mutant was substantially attenuated at viral entry, while it acquired resistance to neutralizing antibodies. 24899172 4 121 theme protein 780:786 arg1 synthesis 788:796 envelope protein synthesis 771:796 envelope protein synthesis 771:796 We observed that the removal of the N146 glycosylation site by mutagenesis was permissive to envelope protein synthesis and stability and to secretion of subviral particles (SVPs) and hepatitis delta virus (HDV) virions, but it was detrimental to HBV virion production. 24899172 10 122 theme essential 2048:2056 arg1 determinant 2058:2068 an essential determinant 2045:2068 an essential determinant of infectivity 2045:2083 IMPORTANCE: At the surface of HBV particles, the immunodominant a-determinant is the main target of neutralizing antibodies and an essential determinant of infectivity. 24899172 10 123 theme main 2002:2005 arg1 IMPORTANCE 1917:1926 IMPORTANCE 1917:1926 IMPORTANCE 1917:1926 IMPORTANCE: At the surface of HBV particles, the immunodominant a-determinant is the main target of neutralizing antibodies and an essential determinant of infectivity. 24899172 10 123 theme main 2002:2005 arg1 a-determinant 1981:1993 the immunodominant a-determinant 1962:1993 the immunodominant a-determinant 1962:1993 IMPORTANCE: At the surface of HBV particles, the immunodominant a-determinant is the main target of neutralizing antibodies and an essential determinant of infectivity. 24899172 10 123 theme main 2002:2005 arg1 target 2007:2012 the main target 1998:2012 the main target of neutralizing antibodies 1998:2039 IMPORTANCE: At the surface of HBV particles, the immunodominant a-determinant is the main target of neutralizing antibodies and an essential determinant of infectivity. 24899172 3 124 gly nonglycosylated 652:666 arg1 isoforms 668:675 the glycosylated and nonglycosylated isoforms 631:675 the glycosylated and nonglycosylated isoforms 631:675 Here we investigated the requirement for a precise positioning of N-linked glycan at amino acid 146 and the functions associated with the glycosylated and nonglycosylated isoforms. 24899172 8 125 theme N-glycosylation 1391:1405 arg1 sites 1407:1411 Infectivity-compatible N-glycosylation sites 1368:1411 Infectivity-compatible N-glycosylation sites 1368:1411 Infectivity-compatible N-glycosylation sites could be inserted at 3 positions (positions 115, 129, and 136), but when all three positions were glycosylated, the hyperglycosylated mutant was substantially attenuated at viral entry, while it acquired resistance to neutralizing antibodies. 24554659 11 0 from antibodies 1938:1947 arg1 escape 1884:1889 the escape 1880:1889 the escape of macrophage-tropic viruses from neutralizing antibodies 1880:1947 This mechanism may facilitate the escape of macrophage-tropic viruses from neutralizing antibodies while promoting spreading infection by these viruses in vivo. 24554659 4 1 attach removal 956:962 arg3 SIVmac239 975:983 SIVmac239 975:983 SIVmac239 975:983 The removal of N173 in SIVmac239 enhanced CD4-independent cell-to-cell transmission to CCR5-expressing cells. 24554659 4 1 attach removal 956:962 arg2 N173 967:970 N173 967:970 N173 967:970 The removal of N173 in SIVmac239 enhanced CD4-independent cell-to-cell transmission to CCR5-expressing cells. 24554659 6 2 located detected 1231:1238 arg1 context 1252:1258 the context 1248:1258 the context of cell-to-cell contact 1248:1282 Thus, CD4-independent phenotypes were detected only in the context of cell-to-cell contact. 24554659 6 2 located detected 1231:1238 arg2 phenotypes 1215:1224 CD4-independent phenotypes 1199:1224 CD4-independent phenotypes 1199:1224 Thus, CD4-independent phenotypes were detected only in the context of cell-to-cell contact. 24554659 9 3 theme N173Q 1480:1484 arg1 mutation 1486:1493 The N173Q mutation 1476:1493 The N173Q mutation 1476:1493 The N173Q mutation had no effect on SIVmac239 binding to CD4 in Biacore assays, coimmunoprecipitation assays, and enzyme-linked immunosorbent assays (ELISAs). 24554659 3 4 theme site 705:708 arg1 Loss 674:677 Loss 674:677 Loss of the N173 glycosylation site in the non-macrophage-tropic SIVmac239 by introducing an N173Q mutation 674:780 Loss of the N173 glycosylation site in the non-macrophage-tropic SIVmac239 by introducing an N173Q mutation enhanced viral replication and multinucleated giant cell formation upon infection of rhesus macrophages, while the addition of N173 to SIVmac251 had the opposite effect. 24554659 13 5 theme increased 2284:2292 arg1 fusion 2307:2312 increased cell-to-cell fusion 2284:2312 increased cell-to-cell fusion 2284:2312 This effect is explained by a novel mechanism involving increased cell-to-cell fusion in the absence of CD4, the primary receptor that normally mediates virus entry. 24554659 3 6 theme N173 686:689 arg1 site 705:708 the N173 glycosylation site 682:708 the N173 glycosylation site in the non-macrophage-tropic SIVmac239 682:747 Loss of the N173 glycosylation site in the non-macrophage-tropic SIVmac239 by introducing an N173Q mutation enhanced viral replication and multinucleated giant cell formation upon infection of rhesus macrophages, while the addition of N173 to SIVmac251 had the opposite effect. 24554659 13 7 theme novel 2258:2262 arg1 mechanism 2264:2272 a novel mechanism 2256:2272 a novel mechanism involving increased cell-to-cell fusion in the absence of CD4, the primary receptor that normally mediates virus entry 2256:2391 This effect is explained by a novel mechanism involving increased cell-to-cell fusion in the absence of CD4, the primary receptor that normally mediates virus entry. 24554659 9 8 contain had 1495:1497 arg1 mutation 1486:1493 The N173Q mutation 1476:1493 The N173Q mutation 1476:1493 The N173Q mutation had no effect on SIVmac239 binding to CD4 in Biacore assays, coimmunoprecipitation assays, and enzyme-linked immunosorbent assays (ELISAs). 24554659 9 8 contain had 1495:1497 arg2 effect 1502:1507 no effect 1499:1507 no effect 1499:1507 The N173Q mutation had no effect on SIVmac239 binding to CD4 in Biacore assays, coimmunoprecipitation assays, and enzyme-linked immunosorbent assays (ELISAs). 24554659 1 9 theme Human 202:206 arg1 HIV 232:234 HIV 232:234 HIV 232:234 Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) strains differ in their capacity to replicate in macrophages, but mechanisms underlying these differences are not fully understood. 24554659 1 9 theme Human 202:206 arg1 virus 225:229 Human immunodeficiency virus 202:229 Human immunodeficiency virus (HIV) 202:235 Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) strains differ in their capacity to replicate in macrophages, but mechanisms underlying these differences are not fully understood. 24554659 2 10 theme novel 579:583 arg1 site 469:472 a highly conserved N-linked glycosylation site 427:472 a highly conserved N-linked glycosylation site (N173 in SIV, corresponding to N160 in HIV) in the V2 region of the SIV envelope glycoprotein (Env) 427:572 Here, we identify a highly conserved N-linked glycosylation site (N173 in SIV, corresponding to N160 in HIV) in the V2 region of the SIV envelope glycoprotein (Env) as a novel determinant of macrophage tropism and characterize mechanisms underlying this phenotype. 24554659 2 10 theme novel 579:583 arg1 determinant 585:595 a novel determinant 577:595 a novel determinant of macrophage tropism 577:617 Here, we identify a highly conserved N-linked glycosylation site (N173 in SIV, corresponding to N160 in HIV) in the V2 region of the SIV envelope glycoprotein (Env) as a novel determinant of macrophage tropism and characterize mechanisms underlying this phenotype. 24554659 6 11 theme CD4-independent 1199:1213 arg1 phenotypes 1215:1224 CD4-independent phenotypes 1199:1224 CD4-independent phenotypes 1199:1224 Thus, CD4-independent phenotypes were detected only in the context of cell-to-cell contact. 24554659 10 12 link N-linked 1684:1691 arg1 site 1707:1710 the N173 N-linked glycosylation site 1675:1710 the N173 N-linked glycosylation site 1675:1710 These findings suggest that the loss of the N173 N-linked glycosylation site increases SIVmac239 replication in macrophages by enhancing CD4-independent cell-to-cell virus transmission through CCR5-mediated fusion. 24554659 1 13 theme virus 225:229 arg1 strains 277:283 Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) strains 202:283 Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) strains 202:283 Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) strains differ in their capacity to replicate in macrophages, but mechanisms underlying these differences are not fully understood. 24554659 3 14 contain had 927:929 arg2 effect 944:949 the opposite effect 931:949 the opposite effect 931:949 Loss of the N173 glycosylation site in the non-macrophage-tropic SIVmac239 by introducing an N173Q mutation enhanced viral replication and multinucleated giant cell formation upon infection of rhesus macrophages, while the addition of N173 to SIVmac251 had the opposite effect. 24554659 3 14 contain had 927:929 arg1 addition 897:904 the addition 893:904 the addition of N173 to SIVmac251 893:925 Loss of the N173 glycosylation site in the non-macrophage-tropic SIVmac239 by introducing an N173Q mutation enhanced viral replication and multinucleated giant cell formation upon infection of rhesus macrophages, while the addition of N173 to SIVmac251 had the opposite effect. 24554659 0 15 link N-linked 20:27 arg1 site 43:46 a conserved N-linked glycosylation site 8:46 a conserved N-linked glycosylation site 8:46 Loss of a conserved N-linked glycosylation site in the simian immunodeficiency virus envelope glycoprotein V2 region enhances macrophage tropism by increasing CD4-independent cell-to-cell transmission. 24554659 11 16 theme macrophage-tropic 1894:1910 arg1 viruses 1912:1918 macrophage-tropic viruses 1894:1918 macrophage-tropic viruses 1894:1918 This mechanism may facilitate the escape of macrophage-tropic viruses from neutralizing antibodies while promoting spreading infection by these viruses in vivo. 24554659 5 17 theme CD4-independent 1092:1106 arg1 fusion 1118:1123 CD4-independent cell-cell fusion 1092:1123 CD4-independent cell-cell fusion 1092:1123 SIVmac239 with N173Q mediated CD4-independent cell-cell fusion but could not infect CD4-negative cells in single-round infections. 24554659 2 18 theme V2 525:526 arg1 region 528:533 the V2 region 521:533 the V2 region of the SIV envelope glycoprotein (Env) 521:572 Here, we identify a highly conserved N-linked glycosylation site (N173 in SIV, corresponding to N160 in HIV) in the V2 region of the SIV envelope glycoprotein (Env) as a novel determinant of macrophage tropism and characterize mechanisms underlying this phenotype. 24554659 3 19 from Loss 674:677 arg1 SIVmac239 739:747 the non-macrophage-tropic SIVmac239 713:747 the non-macrophage-tropic SIVmac239 713:747 Loss of the N173 glycosylation site in the non-macrophage-tropic SIVmac239 by introducing an N173Q mutation enhanced viral replication and multinucleated giant cell formation upon infection of rhesus macrophages, while the addition of N173 to SIVmac251 had the opposite effect. 24554659 3 20 theme N173Q 767:771 arg1 mutation 773:780 an N173Q mutation 764:780 an N173Q mutation 764:780 Loss of the N173 glycosylation site in the non-macrophage-tropic SIVmac239 by introducing an N173Q mutation enhanced viral replication and multinucleated giant cell formation upon infection of rhesus macrophages, while the addition of N173 to SIVmac251 had the opposite effect. 24554659 2 21 theme glycoprotein 555:566 arg1 region 528:533 the V2 region 521:533 the V2 region of the SIV envelope glycoprotein (Env) 521:572 Here, we identify a highly conserved N-linked glycosylation site (N173 in SIV, corresponding to N160 in HIV) in the V2 region of the SIV envelope glycoprotein (Env) as a novel determinant of macrophage tropism and characterize mechanisms underlying this phenotype. 24554659 6 22 theme contact 1276:1282 arg1 context 1252:1258 the context 1248:1258 the context of cell-to-cell contact 1248:1282 Thus, CD4-independent phenotypes were detected only in the context of cell-to-cell contact. 24554659 13 23 theme cell-to-cell 2294:2305 arg1 fusion 2307:2312 increased cell-to-cell fusion 2284:2312 increased cell-to-cell fusion 2284:2312 This effect is explained by a novel mechanism involving increased cell-to-cell fusion in the absence of CD4, the primary receptor that normally mediates virus entry. 24554659 16 24 from antibodies 2745:2754 arg1 escape 2691:2696 the escape 2687:2696 the escape of macrophage-tropic viruses from neutralizing antibodies 2687:2754 Together, these findings suggest that this efficient mode of virus transmission may facilitate the escape of macrophage-tropic viruses from neutralizing antibodies while promoting spreading infection by these viruses to cells expressing little or no CD4 in vivo. 24554659 2 25 gly glycoprotein 555:566 arg1 Env 569:571 Env 569:571 Env 569:571 Here, we identify a highly conserved N-linked glycosylation site (N173 in SIV, corresponding to N160 in HIV) in the V2 region of the SIV envelope glycoprotein (Env) as a novel determinant of macrophage tropism and characterize mechanisms underlying this phenotype. 24554659 2 25 gly glycoprotein 555:566 arg1 glycoprotein 555:566 the SIV envelope glycoprotein 538:566 the SIV envelope glycoprotein (Env) 538:572 Here, we identify a highly conserved N-linked glycosylation site (N173 in SIV, corresponding to N160 in HIV) in the V2 region of the SIV envelope glycoprotein (Env) as a novel determinant of macrophage tropism and characterize mechanisms underlying this phenotype. 24554659 2 26 theme SIV 542:544 arg1 Env 569:571 Env 569:571 Env 569:571 Here, we identify a highly conserved N-linked glycosylation site (N173 in SIV, corresponding to N160 in HIV) in the V2 region of the SIV envelope glycoprotein (Env) as a novel determinant of macrophage tropism and characterize mechanisms underlying this phenotype. 24554659 2 26 theme SIV 542:544 arg1 glycoprotein 555:566 the SIV envelope glycoprotein 538:566 the SIV envelope glycoprotein (Env) 538:572 Here, we identify a highly conserved N-linked glycosylation site (N173 in SIV, corresponding to N160 in HIV) in the V2 region of the SIV envelope glycoprotein (Env) as a novel determinant of macrophage tropism and characterize mechanisms underlying this phenotype. 24554659 12 27 theme virus 2208:2212 arg1 transmission 2214:2225 cell-to-cell virus transmission 2195:2225 cell-to-cell virus transmission 2195:2225 IMPORTANCE: In this study, we identify a genetic determinant in the viral envelope (N173) that increases replication and spreading infection of SIV strains in macrophages by enhancing cell-to-cell virus transmission. 24554659 0 28 theme cell-to-cell 175:186 arg1 transmission 188:199 CD4-independent cell-to-cell transmission 159:199 CD4-independent cell-to-cell transmission 159:199 Loss of a conserved N-linked glycosylation site in the simian immunodeficiency virus envelope glycoprotein V2 region enhances macrophage tropism by increasing CD4-independent cell-to-cell transmission. 24554659 10 29 gly glycosylation 1693:1705 arg2 site 1707:1710 the N173 N-linked glycosylation site 1675:1710 the N173 N-linked glycosylation site 1675:1710 These findings suggest that the loss of the N173 N-linked glycosylation site increases SIVmac239 replication in macrophages by enhancing CD4-independent cell-to-cell virus transmission through CCR5-mediated fusion. 24554659 15 30 theme macrophage-tropic 2516:2532 arg1 strains 2542:2548 Most macrophage-tropic HIV/SIV strains 2511:2548 Most macrophage-tropic HIV/SIV strains 2511:2548 Most macrophage-tropic HIV/SIV strains are known to be neutralization sensitive. 24554659 9 31 theme coimmunoprecipitation 1556:1576 arg1 assays 1578:1583 coimmunoprecipitation assays 1556:1583 coimmunoprecipitation assays 1556:1583 The N173Q mutation had no effect on SIVmac239 binding to CD4 in Biacore assays, coimmunoprecipitation assays, and enzyme-linked immunosorbent assays (ELISAs). 24554659 4 32 theme N173 967:970 arg1 removal 956:962 The removal 952:962 The removal of N173 in SIVmac239 952:983 The removal of N173 in SIVmac239 enhanced CD4-independent cell-to-cell transmission to CCR5-expressing cells. 24554659 8 33 theme neutralization 1370:1383 arg1 sensitivity 1385:1395 the neutralization sensitivity 1366:1395 the neutralization sensitivity of SIVmac251 1366:1408 N173 decreased the neutralization sensitivity of SIVmac251 but had no effect on the neutralization sensitivity of SIVmac239. 24554659 7 34 theme Similar 1285:1291 arg1 results 1293:1299 Similar results 1285:1299 Similar results 1285:1299 Similar results were obtained in SIVmac251 with and without N173. 24554659 16 35 theme macrophage-tropic 2701:2717 arg1 viruses 2719:2725 macrophage-tropic viruses 2701:2725 macrophage-tropic viruses 2701:2725 Together, these findings suggest that this efficient mode of virus transmission may facilitate the escape of macrophage-tropic viruses from neutralizing antibodies while promoting spreading infection by these viruses to cells expressing little or no CD4 in vivo. 24554659 3 36 theme cell 834:837 arg1 formation 839:847 multinucleated giant cell formation 813:847 multinucleated giant cell formation 813:847 Loss of the N173 glycosylation site in the non-macrophage-tropic SIVmac239 by introducing an N173Q mutation enhanced viral replication and multinucleated giant cell formation upon infection of rhesus macrophages, while the addition of N173 to SIVmac251 had the opposite effect. 24554659 0 37 theme immunodeficiency 62:77 arg1 glycoprotein 94:105 the simian immunodeficiency virus envelope glycoprotein 51:105 the simian immunodeficiency virus envelope glycoprotein V2 region 51:115 Loss of a conserved N-linked glycosylation site in the simian immunodeficiency virus envelope glycoprotein V2 region enhances macrophage tropism by increasing CD4-independent cell-to-cell transmission. 24554659 5 38 theme single-round 1168:1179 arg1 infections 1181:1190 single-round infections 1168:1190 single-round infections 1168:1190 SIVmac239 with N173Q mediated CD4-independent cell-cell fusion but could not infect CD4-negative cells in single-round infections. 24554659 9 39 theme enzyme-linked 1590:1602 arg1 ELISAs 1626:1631 ELISAs 1626:1631 ELISAs 1626:1631 The N173Q mutation had no effect on SIVmac239 binding to CD4 in Biacore assays, coimmunoprecipitation assays, and enzyme-linked immunosorbent assays (ELISAs). 24554659 9 39 theme enzyme-linked 1590:1602 arg1 assays 1618:1623 enzyme-linked immunosorbent assays 1590:1623 enzyme-linked immunosorbent assays (ELISAs) 1590:1632 The N173Q mutation had no effect on SIVmac239 binding to CD4 in Biacore assays, coimmunoprecipitation assays, and enzyme-linked immunosorbent assays (ELISAs). 24554659 3 40 theme macrophages 874:884 arg1 infection 854:862 infection 854:862 infection of rhesus macrophages 854:884 Loss of the N173 glycosylation site in the non-macrophage-tropic SIVmac239 by introducing an N173Q mutation enhanced viral replication and multinucleated giant cell formation upon infection of rhesus macrophages, while the addition of N173 to SIVmac251 had the opposite effect. 24554659 8 41 contain had 1414:1416 arg1 N173 1351:1354 N173 1351:1354 N173 1351:1354 N173 decreased the neutralization sensitivity of SIVmac251 but had no effect on the neutralization sensitivity of SIVmac239. 24554659 8 41 contain had 1414:1416 arg2 effect 1421:1426 no effect 1418:1426 no effect 1418:1426 N173 decreased the neutralization sensitivity of SIVmac251 but had no effect on the neutralization sensitivity of SIVmac239. 24554659 0 42 from Loss 0:3 arg1 region 110:115 the simian immunodeficiency virus envelope glycoprotein V2 region 51:115 the simian immunodeficiency virus envelope glycoprotein V2 region 51:115 Loss of a conserved N-linked glycosylation site in the simian immunodeficiency virus envelope glycoprotein V2 region enhances macrophage tropism by increasing CD4-independent cell-to-cell transmission. 24554659 3 43 theme multinucleated 813:826 arg1 formation 839:847 multinucleated giant cell formation 813:847 multinucleated giant cell formation 813:847 Loss of the N173 glycosylation site in the non-macrophage-tropic SIVmac239 by introducing an N173Q mutation enhanced viral replication and multinucleated giant cell formation upon infection of rhesus macrophages, while the addition of N173 to SIVmac251 had the opposite effect. 24554659 0 44 theme envelope 85:92 arg1 glycoprotein 94:105 the simian immunodeficiency virus envelope glycoprotein 51:105 the simian immunodeficiency virus envelope glycoprotein V2 region 51:115 Loss of a conserved N-linked glycosylation site in the simian immunodeficiency virus envelope glycoprotein V2 region enhances macrophage tropism by increasing CD4-independent cell-to-cell transmission. 24554659 3 45 theme N173 909:912 arg1 addition 897:904 the addition 893:904 the addition of N173 to SIVmac251 893:925 Loss of the N173 glycosylation site in the non-macrophage-tropic SIVmac239 by introducing an N173Q mutation enhanced viral replication and multinucleated giant cell formation upon infection of rhesus macrophages, while the addition of N173 to SIVmac251 had the opposite effect. 24554659 2 46 theme macrophage 600:609 arg1 tropism 611:617 macrophage tropism 600:617 macrophage tropism 600:617 Here, we identify a highly conserved N-linked glycosylation site (N173 in SIV, corresponding to N160 in HIV) in the V2 region of the SIV envelope glycoprotein (Env) as a novel determinant of macrophage tropism and characterize mechanisms underlying this phenotype. 24554659 14 47 theme same 2398:2401 arg1 determinant 2411:2421 The same genetic determinant 2394:2421 The same genetic determinant 2394:2421 The same genetic determinant also affects the sensitivity of these viruses to inhibition by neutralizing antibodies. 24554659 10 48 theme SIVmac239 1722:1730 arg1 replication 1732:1742 SIVmac239 replication 1722:1742 SIVmac239 replication in macrophages 1722:1757 These findings suggest that the loss of the N173 N-linked glycosylation site increases SIVmac239 replication in macrophages by enhancing CD4-independent cell-to-cell virus transmission through CCR5-mediated fusion. 24554659 0 49 theme V2 107:108 arg1 region 110:115 the simian immunodeficiency virus envelope glycoprotein V2 region 51:115 the simian immunodeficiency virus envelope glycoprotein V2 region 51:115 Loss of a conserved N-linked glycosylation site in the simian immunodeficiency virus envelope glycoprotein V2 region enhances macrophage tropism by increasing CD4-independent cell-to-cell transmission. 24554659 15 50 theme HIV/SIV 2534:2540 arg1 strains 2542:2548 Most macrophage-tropic HIV/SIV strains 2511:2548 Most macrophage-tropic HIV/SIV strains 2511:2548 Most macrophage-tropic HIV/SIV strains are known to be neutralization sensitive. 24554659 4 51 theme CCR5-expressing 1039:1053 arg1 cells 1055:1059 CCR5-expressing cells 1039:1059 CCR5-expressing cells 1039:1059 The removal of N173 in SIVmac239 enhanced CD4-independent cell-to-cell transmission to CCR5-expressing cells. 24554659 3 52 from SIVmac239 739:747 arg1 Loss 674:677 Loss 674:677 Loss of the N173 glycosylation site in the non-macrophage-tropic SIVmac239 by introducing an N173Q mutation 674:780 Loss of the N173 glycosylation site in the non-macrophage-tropic SIVmac239 by introducing an N173Q mutation enhanced viral replication and multinucleated giant cell formation upon infection of rhesus macrophages, while the addition of N173 to SIVmac251 had the opposite effect. 24554659 10 53 theme site 1707:1710 arg1 loss 1667:1670 the loss 1663:1670 the loss of the N173 N-linked glycosylation site 1663:1710 These findings suggest that the loss of the N173 N-linked glycosylation site increases SIVmac239 replication in macrophages by enhancing CD4-independent cell-to-cell virus transmission through CCR5-mediated fusion. 24554659 0 54 gly glycoprotein 94:105 arg1 glycoprotein 94:105 the simian immunodeficiency virus envelope glycoprotein 51:105 the simian immunodeficiency virus envelope glycoprotein V2 region 51:115 Loss of a conserved N-linked glycosylation site in the simian immunodeficiency virus envelope glycoprotein V2 region enhances macrophage tropism by increasing CD4-independent cell-to-cell transmission. 24554659 2 55 theme N-linked 446:453 arg1 site 469:472 a highly conserved N-linked glycosylation site 427:472 a highly conserved N-linked glycosylation site (N173 in SIV, corresponding to N160 in HIV) in the V2 region of the SIV envelope glycoprotein (Env) 427:572 Here, we identify a highly conserved N-linked glycosylation site (N173 in SIV, corresponding to N160 in HIV) in the V2 region of the SIV envelope glycoprotein (Env) as a novel determinant of macrophage tropism and characterize mechanisms underlying this phenotype. 24554659 2 55 theme N-linked 446:453 arg1 determinant 585:595 a novel determinant 577:595 a novel determinant of macrophage tropism 577:617 Here, we identify a highly conserved N-linked glycosylation site (N173 in SIV, corresponding to N160 in HIV) in the V2 region of the SIV envelope glycoprotein (Env) as a novel determinant of macrophage tropism and characterize mechanisms underlying this phenotype. 24554659 12 56 dep replication 2116:2126 arg1 infection 2142:2150 infection 2142:2150 infection 2142:2150 IMPORTANCE: In this study, we identify a genetic determinant in the viral envelope (N173) that increases replication and spreading infection of SIV strains in macrophages by enhancing cell-to-cell virus transmission. 24554659 8 57 theme neutralization 1435:1448 arg1 sensitivity 1450:1460 the neutralization sensitivity 1431:1460 the neutralization sensitivity of SIVmac239 1431:1473 N173 decreased the neutralization sensitivity of SIVmac251 but had no effect on the neutralization sensitivity of SIVmac239. 24554659 9 58 link enzyme-linked 1590:1602 arg1 ELISAs 1626:1631 ELISAs 1626:1631 ELISAs 1626:1631 The N173Q mutation had no effect on SIVmac239 binding to CD4 in Biacore assays, coimmunoprecipitation assays, and enzyme-linked immunosorbent assays (ELISAs). 24554659 9 58 link enzyme-linked 1590:1602 arg1 assays 1618:1623 enzyme-linked immunosorbent assays 1590:1623 enzyme-linked immunosorbent assays (ELISAs) 1590:1632 The N173Q mutation had no effect on SIVmac239 binding to CD4 in Biacore assays, coimmunoprecipitation assays, and enzyme-linked immunosorbent assays (ELISAs). 24554659 12 59 theme strains 2159:2165 arg1 spreading 2132:2140 spreading 2132:2140 spreading 2132:2140 IMPORTANCE: In this study, we identify a genetic determinant in the viral envelope (N173) that increases replication and spreading infection of SIV strains in macrophages by enhancing cell-to-cell virus transmission. 24554659 12 59 theme strains 2159:2165 arg1 replication 2116:2126 replication 2116:2126 replication 2116:2126 IMPORTANCE: In this study, we identify a genetic determinant in the viral envelope (N173) that increases replication and spreading infection of SIV strains in macrophages by enhancing cell-to-cell virus transmission. 24554659 4 60 theme CD4-independent 994:1008 arg1 transmission 1023:1034 CD4-independent cell-to-cell transmission 994:1034 CD4-independent cell-to-cell transmission to CCR5-expressing cells 994:1059 The removal of N173 in SIVmac239 enhanced CD4-independent cell-to-cell transmission to CCR5-expressing cells. 24554659 0 61 theme N-linked 20:27 arg1 site 43:46 a conserved N-linked glycosylation site 8:46 a conserved N-linked glycosylation site 8:46 Loss of a conserved N-linked glycosylation site in the simian immunodeficiency virus envelope glycoprotein V2 region enhances macrophage tropism by increasing CD4-independent cell-to-cell transmission. 24554659 16 62 theme virus 2653:2657 arg1 transmission 2659:2670 virus transmission 2653:2670 virus transmission 2653:2670 Together, these findings suggest that this efficient mode of virus transmission may facilitate the escape of macrophage-tropic viruses from neutralizing antibodies while promoting spreading infection by these viruses to cells expressing little or no CD4 in vivo. 24554659 10 63 theme virus 1801:1805 arg1 transmission 1807:1818 CD4-independent cell-to-cell virus transmission 1772:1818 CD4-independent cell-to-cell virus transmission 1772:1818 These findings suggest that the loss of the N173 N-linked glycosylation site increases SIVmac239 replication in macrophages by enhancing CD4-independent cell-to-cell virus transmission through CCR5-mediated fusion. 24554659 0 64 theme site 43:46 arg1 Loss 0:3 Loss 0:3 Loss of a conserved N-linked glycosylation site in the simian immunodeficiency virus envelope glycoprotein V2 region 0:115 Loss of a conserved N-linked glycosylation site in the simian immunodeficiency virus envelope glycoprotein V2 region enhances macrophage tropism by increasing CD4-independent cell-to-cell transmission. 24554659 13 65 theme CD4 2332:2334 arg1 absence 2321:2327 the absence 2317:2327 the absence of CD4, the primary receptor that normally mediates virus entry 2317:2391 This effect is explained by a novel mechanism involving increased cell-to-cell fusion in the absence of CD4, the primary receptor that normally mediates virus entry. 24554659 9 66 from binding 1522:1528 arg1 ELISAs 1626:1631 ELISAs 1626:1631 ELISAs 1626:1631 The N173Q mutation had no effect on SIVmac239 binding to CD4 in Biacore assays, coimmunoprecipitation assays, and enzyme-linked immunosorbent assays (ELISAs). 24554659 9 66 from binding 1522:1528 arg1 assays 1618:1623 enzyme-linked immunosorbent assays 1590:1623 enzyme-linked immunosorbent assays (ELISAs) 1590:1632 The N173Q mutation had no effect on SIVmac239 binding to CD4 in Biacore assays, coimmunoprecipitation assays, and enzyme-linked immunosorbent assays (ELISAs). 24554659 9 66 from binding 1522:1528 arg1 assays 1578:1583 coimmunoprecipitation assays 1556:1583 coimmunoprecipitation assays 1556:1583 The N173Q mutation had no effect on SIVmac239 binding to CD4 in Biacore assays, coimmunoprecipitation assays, and enzyme-linked immunosorbent assays (ELISAs). 24554659 9 66 from binding 1522:1528 arg1 assays 1548:1553 Biacore assays 1540:1553 Biacore assays 1540:1553 The N173Q mutation had no effect on SIVmac239 binding to CD4 in Biacore assays, coimmunoprecipitation assays, and enzyme-linked immunosorbent assays (ELISAs). 24554659 10 67 theme CD4-independent 1772:1786 arg1 transmission 1807:1818 CD4-independent cell-to-cell virus transmission 1772:1818 CD4-independent cell-to-cell virus transmission 1772:1818 These findings suggest that the loss of the N173 N-linked glycosylation site increases SIVmac239 replication in macrophages by enhancing CD4-independent cell-to-cell virus transmission through CCR5-mediated fusion. 24554659 1 68 theme simian 241:246 arg1 virus 265:269 simian immunodeficiency virus 241:269 simian immunodeficiency virus (SIV) 241:275 Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) strains differ in their capacity to replicate in macrophages, but mechanisms underlying these differences are not fully understood. 24554659 1 68 theme simian 241:246 arg1 SIV 272:274 SIV 272:274 SIV 272:274 Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) strains differ in their capacity to replicate in macrophages, but mechanisms underlying these differences are not fully understood. 24554659 12 69 from determinant 2060:2070 arg1 envelope 2085:2092 the viral envelope 2075:2092 the viral envelope (N173) that increases replication and spreading infection of SIV strains in macrophages by enhancing cell-to-cell virus transmission 2075:2225 IMPORTANCE: In this study, we identify a genetic determinant in the viral envelope (N173) that increases replication and spreading infection of SIV strains in macrophages by enhancing cell-to-cell virus transmission. 24554659 12 69 from determinant 2060:2070 arg1 N173 2095:2098 N173 2095:2098 N173 2095:2098 IMPORTANCE: In this study, we identify a genetic determinant in the viral envelope (N173) that increases replication and spreading infection of SIV strains in macrophages by enhancing cell-to-cell virus transmission. 24554659 0 70 gly glycosylation 29:41 arg2 site 43:46 a conserved N-linked glycosylation site 8:46 a conserved N-linked glycosylation site 8:46 Loss of a conserved N-linked glycosylation site in the simian immunodeficiency virus envelope glycoprotein V2 region enhances macrophage tropism by increasing CD4-independent cell-to-cell transmission. 24554659 1 71 theme virus 265:269 arg1 strains 277:283 Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) strains 202:283 Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) strains 202:283 Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) strains differ in their capacity to replicate in macrophages, but mechanisms underlying these differences are not fully understood. 24554659 4 72 from removal 956:962 arg1 SIVmac239 975:983 SIVmac239 975:983 SIVmac239 975:983 The removal of N173 in SIVmac239 enhanced CD4-independent cell-to-cell transmission to CCR5-expressing cells. 24554659 12 73 from spreading 2132:2140 arg1 macrophages 2170:2180 macrophages 2170:2180 macrophages 2170:2180 IMPORTANCE: In this study, we identify a genetic determinant in the viral envelope (N173) that increases replication and spreading infection of SIV strains in macrophages by enhancing cell-to-cell virus transmission. 24554659 12 74 from replication 2116:2126 arg1 macrophages 2170:2180 macrophages 2170:2180 macrophages 2170:2180 IMPORTANCE: In this study, we identify a genetic determinant in the viral envelope (N173) that increases replication and spreading infection of SIV strains in macrophages by enhancing cell-to-cell virus transmission. 24554659 16 75 dep little 2829:2834 arg1 CD4 2842:2844 CD4 2842:2844 CD4 in vivo 2842:2852 Together, these findings suggest that this efficient mode of virus transmission may facilitate the escape of macrophage-tropic viruses from neutralizing antibodies while promoting spreading infection by these viruses to cells expressing little or no CD4 in vivo. 24554659 3 76 theme glycosylation 691:703 arg1 site 705:708 the N173 glycosylation site 682:708 the N173 glycosylation site in the non-macrophage-tropic SIVmac239 682:747 Loss of the N173 glycosylation site in the non-macrophage-tropic SIVmac239 by introducing an N173Q mutation enhanced viral replication and multinucleated giant cell formation upon infection of rhesus macrophages, while the addition of N173 to SIVmac251 had the opposite effect. 24554659 1 77 theme immunodeficiency 208:223 arg1 HIV 232:234 HIV 232:234 HIV 232:234 Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) strains differ in their capacity to replicate in macrophages, but mechanisms underlying these differences are not fully understood. 24554659 1 77 theme immunodeficiency 208:223 arg1 virus 225:229 Human immunodeficiency virus 202:229 Human immunodeficiency virus (HIV) 202:235 Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) strains differ in their capacity to replicate in macrophages, but mechanisms underlying these differences are not fully understood. 24554659 12 78 theme viral 2079:2083 arg1 envelope 2085:2092 the viral envelope 2075:2092 the viral envelope (N173) that increases replication and spreading infection of SIV strains in macrophages by enhancing cell-to-cell virus transmission 2075:2225 IMPORTANCE: In this study, we identify a genetic determinant in the viral envelope (N173) that increases replication and spreading infection of SIV strains in macrophages by enhancing cell-to-cell virus transmission. 24554659 12 78 theme viral 2079:2083 arg1 N173 2095:2098 N173 2095:2098 N173 2095:2098 IMPORTANCE: In this study, we identify a genetic determinant in the viral envelope (N173) that increases replication and spreading infection of SIV strains in macrophages by enhancing cell-to-cell virus transmission. 24554659 16 79 theme spreading 2772:2780 arg1 infection 2782:2790 spreading infection 2772:2790 spreading infection by these viruses to cells expressing little or no CD4 in vivo 2772:2852 Together, these findings suggest that this efficient mode of virus transmission may facilitate the escape of macrophage-tropic viruses from neutralizing antibodies while promoting spreading infection by these viruses to cells expressing little or no CD4 in vivo. 24554659 3 80 from site 705:708 arg1 SIVmac239 739:747 the non-macrophage-tropic SIVmac239 713:747 the non-macrophage-tropic SIVmac239 713:747 Loss of the N173 glycosylation site in the non-macrophage-tropic SIVmac239 by introducing an N173Q mutation enhanced viral replication and multinucleated giant cell formation upon infection of rhesus macrophages, while the addition of N173 to SIVmac251 had the opposite effect. 24554659 11 81 theme neutralizing 1925:1936 arg1 antibodies 1938:1947 neutralizing antibodies 1925:1947 neutralizing antibodies 1925:1947 This mechanism may facilitate the escape of macrophage-tropic viruses from neutralizing antibodies while promoting spreading infection by these viruses in vivo. 24554659 0 82 theme macrophage 126:135 arg1 tropism 137:143 macrophage tropism 126:143 macrophage tropism 126:143 Loss of a conserved N-linked glycosylation site in the simian immunodeficiency virus envelope glycoprotein V2 region enhances macrophage tropism by increasing CD4-independent cell-to-cell transmission. 24554659 10 83 theme N-linked 1684:1691 arg1 site 1707:1710 the N173 N-linked glycosylation site 1675:1710 the N173 N-linked glycosylation site 1675:1710 These findings suggest that the loss of the N173 N-linked glycosylation site increases SIVmac239 replication in macrophages by enhancing CD4-independent cell-to-cell virus transmission through CCR5-mediated fusion. 24554659 3 84 theme non-macrophage-tropic 717:737 arg1 SIVmac239 739:747 the non-macrophage-tropic SIVmac239 713:747 the non-macrophage-tropic SIVmac239 713:747 Loss of the N173 glycosylation site in the non-macrophage-tropic SIVmac239 by introducing an N173Q mutation enhanced viral replication and multinucleated giant cell formation upon infection of rhesus macrophages, while the addition of N173 to SIVmac251 had the opposite effect. 24554659 5 85 theme cell-cell 1108:1116 arg1 fusion 1118:1123 CD4-independent cell-cell fusion 1092:1123 CD4-independent cell-cell fusion 1092:1123 SIVmac239 with N173Q mediated CD4-independent cell-cell fusion but could not infect CD4-negative cells in single-round infections. 24554659 9 86 theme SIVmac239 1512:1520 arg1 binding 1522:1528 SIVmac239 binding 1512:1528 SIVmac239 binding to CD4 in Biacore assays, coimmunoprecipitation assays, and enzyme-linked immunosorbent assays (ELISAs) 1512:1632 The N173Q mutation had no effect on SIVmac239 binding to CD4 in Biacore assays, coimmunoprecipitation assays, and enzyme-linked immunosorbent assays (ELISAs). 24554659 12 87 theme genetic 2052:2058 arg1 determinant 2060:2070 a genetic determinant 2050:2070 a genetic determinant in the viral envelope (N173) that increases replication and spreading infection of SIV strains in macrophages by enhancing cell-to-cell virus transmission 2050:2225 IMPORTANCE: In this study, we identify a genetic determinant in the viral envelope (N173) that increases replication and spreading infection of SIV strains in macrophages by enhancing cell-to-cell virus transmission. 24554659 11 88 theme spreading 1965:1973 arg1 infection 1975:1983 spreading infection 1965:1983 spreading infection by these viruses 1965:2000 This mechanism may facilitate the escape of macrophage-tropic viruses from neutralizing antibodies while promoting spreading infection by these viruses in vivo. 24554659 0 89 theme CD4-independent 159:173 arg1 transmission 188:199 CD4-independent cell-to-cell transmission 159:199 CD4-independent cell-to-cell transmission 159:199 Loss of a conserved N-linked glycosylation site in the simian immunodeficiency virus envelope glycoprotein V2 region enhances macrophage tropism by increasing CD4-independent cell-to-cell transmission. 24554659 9 90 theme Biacore 1540:1546 arg1 assays 1548:1553 Biacore assays 1540:1553 Biacore assays 1540:1553 The N173Q mutation had no effect on SIVmac239 binding to CD4 in Biacore assays, coimmunoprecipitation assays, and enzyme-linked immunosorbent assays (ELISAs). 24554659 2 91 theme envelope 546:553 arg1 Env 569:571 Env 569:571 Env 569:571 Here, we identify a highly conserved N-linked glycosylation site (N173 in SIV, corresponding to N160 in HIV) in the V2 region of the SIV envelope glycoprotein (Env) as a novel determinant of macrophage tropism and characterize mechanisms underlying this phenotype. 24554659 2 91 theme envelope 546:553 arg1 glycoprotein 555:566 the SIV envelope glycoprotein 538:566 the SIV envelope glycoprotein (Env) 538:572 Here, we identify a highly conserved N-linked glycosylation site (N173 in SIV, corresponding to N160 in HIV) in the V2 region of the SIV envelope glycoprotein (Env) as a novel determinant of macrophage tropism and characterize mechanisms underlying this phenotype. 24554659 6 92 theme cell-to-cell 1263:1274 arg1 contact 1276:1282 cell-to-cell contact 1263:1282 cell-to-cell contact 1263:1282 Thus, CD4-independent phenotypes were detected only in the context of cell-to-cell contact. 24554659 14 93 theme viruses 2461:2467 arg1 sensitivity 2440:2450 the sensitivity 2436:2450 the sensitivity of these viruses to inhibition 2436:2481 The same genetic determinant also affects the sensitivity of these viruses to inhibition by neutralizing antibodies. 24554659 3 94 theme rhesus 867:872 arg1 macrophages 874:884 rhesus macrophages 867:884 rhesus macrophages 867:884 Loss of the N173 glycosylation site in the non-macrophage-tropic SIVmac239 by introducing an N173Q mutation enhanced viral replication and multinucleated giant cell formation upon infection of rhesus macrophages, while the addition of N173 to SIVmac251 had the opposite effect. 24554659 12 95 theme cell-to-cell 2195:2206 arg1 transmission 2214:2225 cell-to-cell virus transmission 2195:2225 cell-to-cell virus transmission 2195:2225 IMPORTANCE: In this study, we identify a genetic determinant in the viral envelope (N173) that increases replication and spreading infection of SIV strains in macrophages by enhancing cell-to-cell virus transmission. 24554659 0 96 theme simian 55:60 arg1 glycoprotein 94:105 the simian immunodeficiency virus envelope glycoprotein 51:105 the simian immunodeficiency virus envelope glycoprotein V2 region 51:115 Loss of a conserved N-linked glycosylation site in the simian immunodeficiency virus envelope glycoprotein V2 region enhances macrophage tropism by increasing CD4-independent cell-to-cell transmission. 24554659 16 97 theme viruses 2719:2725 arg1 escape 2691:2696 the escape 2687:2696 the escape of macrophage-tropic viruses from neutralizing antibodies 2687:2754 Together, these findings suggest that this efficient mode of virus transmission may facilitate the escape of macrophage-tropic viruses from neutralizing antibodies while promoting spreading infection by these viruses to cells expressing little or no CD4 in vivo. 24554659 12 98 theme SIV 2155:2157 arg1 strains 2159:2165 SIV strains 2155:2165 SIV strains 2155:2165 IMPORTANCE: In this study, we identify a genetic determinant in the viral envelope (N173) that increases replication and spreading infection of SIV strains in macrophages by enhancing cell-to-cell virus transmission. 24554659 3 99 theme viral 791:795 arg1 replication 797:807 viral replication 791:807 viral replication 791:807 Loss of the N173 glycosylation site in the non-macrophage-tropic SIVmac239 by introducing an N173Q mutation enhanced viral replication and multinucleated giant cell formation upon infection of rhesus macrophages, while the addition of N173 to SIVmac251 had the opposite effect. 24554659 0 100 theme virus 79:83 arg1 glycoprotein 94:105 the simian immunodeficiency virus envelope glycoprotein 51:105 the simian immunodeficiency virus envelope glycoprotein V2 region 51:115 Loss of a conserved N-linked glycosylation site in the simian immunodeficiency virus envelope glycoprotein V2 region enhances macrophage tropism by increasing CD4-independent cell-to-cell transmission. 24554659 13 101 theme virus 2381:2385 arg1 entry 2387:2391 virus entry 2381:2391 virus entry 2381:2391 This effect is explained by a novel mechanism involving increased cell-to-cell fusion in the absence of CD4, the primary receptor that normally mediates virus entry. 24554659 16 102 theme neutralizing 2732:2743 arg1 antibodies 2745:2754 neutralizing antibodies 2732:2754 neutralizing antibodies 2732:2754 Together, these findings suggest that this efficient mode of virus transmission may facilitate the escape of macrophage-tropic viruses from neutralizing antibodies while promoting spreading infection by these viruses to cells expressing little or no CD4 in vivo. 24554659 2 103 from site 469:472 arg1 region 528:533 the V2 region 521:533 the V2 region of the SIV envelope glycoprotein (Env) 521:572 Here, we identify a highly conserved N-linked glycosylation site (N173 in SIV, corresponding to N160 in HIV) in the V2 region of the SIV envelope glycoprotein (Env) as a novel determinant of macrophage tropism and characterize mechanisms underlying this phenotype. 24554659 2 104 link N-linked 446:453 arg1 site 469:472 a highly conserved N-linked glycosylation site 427:472 a highly conserved N-linked glycosylation site (N173 in SIV, corresponding to N160 in HIV) in the V2 region of the SIV envelope glycoprotein (Env) 427:572 Here, we identify a highly conserved N-linked glycosylation site (N173 in SIV, corresponding to N160 in HIV) in the V2 region of the SIV envelope glycoprotein (Env) as a novel determinant of macrophage tropism and characterize mechanisms underlying this phenotype. 24554659 2 104 link N-linked 446:453 arg1 determinant 585:595 a novel determinant 577:595 a novel determinant of macrophage tropism 577:617 Here, we identify a highly conserved N-linked glycosylation site (N173 in SIV, corresponding to N160 in HIV) in the V2 region of the SIV envelope glycoprotein (Env) as a novel determinant of macrophage tropism and characterize mechanisms underlying this phenotype. 24554659 15 105 theme Most 2511:2514 arg1 strains 2542:2548 Most macrophage-tropic HIV/SIV strains 2511:2548 Most macrophage-tropic HIV/SIV strains 2511:2548 Most macrophage-tropic HIV/SIV strains are known to be neutralization sensitive. 24554659 0 106 theme glycoprotein 94:105 arg1 region 110:115 the simian immunodeficiency virus envelope glycoprotein V2 region 51:115 the simian immunodeficiency virus envelope glycoprotein V2 region 51:115 Loss of a conserved N-linked glycosylation site in the simian immunodeficiency virus envelope glycoprotein V2 region enhances macrophage tropism by increasing CD4-independent cell-to-cell transmission. 24554659 9 107 theme immunosorbent 1604:1616 arg1 ELISAs 1626:1631 ELISAs 1626:1631 ELISAs 1626:1631 The N173Q mutation had no effect on SIVmac239 binding to CD4 in Biacore assays, coimmunoprecipitation assays, and enzyme-linked immunosorbent assays (ELISAs). 24554659 9 107 theme immunosorbent 1604:1616 arg1 assays 1618:1623 enzyme-linked immunosorbent assays 1590:1623 enzyme-linked immunosorbent assays (ELISAs) 1590:1632 The N173Q mutation had no effect on SIVmac239 binding to CD4 in Biacore assays, coimmunoprecipitation assays, and enzyme-linked immunosorbent assays (ELISAs). 24554659 2 108 from N173 475:478 arg1 SIV 483:485 SIV 483:485 SIV 483:485 Here, we identify a highly conserved N-linked glycosylation site (N173 in SIV, corresponding to N160 in HIV) in the V2 region of the SIV envelope glycoprotein (Env) as a novel determinant of macrophage tropism and characterize mechanisms underlying this phenotype. 24554659 2 109 theme tropism 611:617 arg1 site 469:472 a highly conserved N-linked glycosylation site 427:472 a highly conserved N-linked glycosylation site (N173 in SIV, corresponding to N160 in HIV) in the V2 region of the SIV envelope glycoprotein (Env) 427:572 Here, we identify a highly conserved N-linked glycosylation site (N173 in SIV, corresponding to N160 in HIV) in the V2 region of the SIV envelope glycoprotein (Env) as a novel determinant of macrophage tropism and characterize mechanisms underlying this phenotype. 24554659 2 109 theme tropism 611:617 arg1 determinant 585:595 a novel determinant 577:595 a novel determinant of macrophage tropism 577:617 Here, we identify a highly conserved N-linked glycosylation site (N173 in SIV, corresponding to N160 in HIV) in the V2 region of the SIV envelope glycoprotein (Env) as a novel determinant of macrophage tropism and characterize mechanisms underlying this phenotype. 24554659 8 110 theme SIVmac251 1400:1408 arg1 sensitivity 1385:1395 the neutralization sensitivity 1366:1395 the neutralization sensitivity of SIVmac251 1366:1408 N173 decreased the neutralization sensitivity of SIVmac251 but had no effect on the neutralization sensitivity of SIVmac239. 24554659 14 111 theme genetic 2403:2409 arg1 determinant 2411:2421 The same genetic determinant 2394:2421 The same genetic determinant 2394:2421 The same genetic determinant also affects the sensitivity of these viruses to inhibition by neutralizing antibodies. 24554659 3 112 theme giant 828:832 arg1 formation 839:847 multinucleated giant cell formation 813:847 multinucleated giant cell formation 813:847 Loss of the N173 glycosylation site in the non-macrophage-tropic SIVmac239 by introducing an N173Q mutation enhanced viral replication and multinucleated giant cell formation upon infection of rhesus macrophages, while the addition of N173 to SIVmac251 had the opposite effect. 24554659 11 113 theme viruses 1912:1918 arg1 escape 1884:1889 the escape 1880:1889 the escape of macrophage-tropic viruses from neutralizing antibodies 1880:1947 This mechanism may facilitate the escape of macrophage-tropic viruses from neutralizing antibodies while promoting spreading infection by these viruses in vivo. 24554659 5 114 with SIVmac239 1062:1070 arg1 N173Q 1077:1081 N173Q 1077:1081 N173Q 1077:1081 SIVmac239 with N173Q mediated CD4-independent cell-cell fusion but could not infect CD4-negative cells in single-round infections. 24554659 5 115 theme CD4-negative 1146:1157 arg1 cells 1159:1163 CD4-negative cells 1146:1163 CD4-negative cells in single-round infections 1146:1190 SIVmac239 with N173Q mediated CD4-independent cell-cell fusion but could not infect CD4-negative cells in single-round infections. 24554659 2 116 dep site 469:472 arg1 N173 475:478 N173 475:478 N173 in SIV, corresponding to N160 in HIV 475:515 Here, we identify a highly conserved N-linked glycosylation site (N173 in SIV, corresponding to N160 in HIV) in the V2 region of the SIV envelope glycoprotein (Env) as a novel determinant of macrophage tropism and characterize mechanisms underlying this phenotype. 24554659 2 117 theme glycosylation 455:467 arg1 site 469:472 a highly conserved N-linked glycosylation site 427:472 a highly conserved N-linked glycosylation site (N173 in SIV, corresponding to N160 in HIV) in the V2 region of the SIV envelope glycoprotein (Env) 427:572 Here, we identify a highly conserved N-linked glycosylation site (N173 in SIV, corresponding to N160 in HIV) in the V2 region of the SIV envelope glycoprotein (Env) as a novel determinant of macrophage tropism and characterize mechanisms underlying this phenotype. 24554659 2 117 theme glycosylation 455:467 arg1 determinant 585:595 a novel determinant 577:595 a novel determinant of macrophage tropism 577:617 Here, we identify a highly conserved N-linked glycosylation site (N173 in SIV, corresponding to N160 in HIV) in the V2 region of the SIV envelope glycoprotein (Env) as a novel determinant of macrophage tropism and characterize mechanisms underlying this phenotype. 24554659 10 118 theme glycosylation 1693:1705 arg1 site 1707:1710 the N173 N-linked glycosylation site 1675:1710 the N173 N-linked glycosylation site 1675:1710 These findings suggest that the loss of the N173 N-linked glycosylation site increases SIVmac239 replication in macrophages by enhancing CD4-independent cell-to-cell virus transmission through CCR5-mediated fusion. 24554659 0 119 theme conserved 10:18 arg1 site 43:46 a conserved N-linked glycosylation site 8:46 a conserved N-linked glycosylation site 8:46 Loss of a conserved N-linked glycosylation site in the simian immunodeficiency virus envelope glycoprotein V2 region enhances macrophage tropism by increasing CD4-independent cell-to-cell transmission. 24554659 13 120 theme primary 2341:2347 arg1 CD4 2332:2334 CD4 2332:2334 CD4 2332:2334 This effect is explained by a novel mechanism involving increased cell-to-cell fusion in the absence of CD4, the primary receptor that normally mediates virus entry. 24554659 13 120 theme primary 2341:2347 arg1 receptor 2349:2356 the primary receptor 2337:2356 the primary receptor that normally mediates virus entry 2337:2391 This effect is explained by a novel mechanism involving increased cell-to-cell fusion in the absence of CD4, the primary receptor that normally mediates virus entry. 24554659 3 121 theme opposite 935:942 arg1 effect 944:949 the opposite effect 931:949 the opposite effect 931:949 Loss of the N173 glycosylation site in the non-macrophage-tropic SIVmac239 by introducing an N173Q mutation enhanced viral replication and multinucleated giant cell formation upon infection of rhesus macrophages, while the addition of N173 to SIVmac251 had the opposite effect. 24554659 2 122 theme conserved 436:444 arg1 site 469:472 a highly conserved N-linked glycosylation site 427:472 a highly conserved N-linked glycosylation site (N173 in SIV, corresponding to N160 in HIV) in the V2 region of the SIV envelope glycoprotein (Env) 427:572 Here, we identify a highly conserved N-linked glycosylation site (N173 in SIV, corresponding to N160 in HIV) in the V2 region of the SIV envelope glycoprotein (Env) as a novel determinant of macrophage tropism and characterize mechanisms underlying this phenotype. 24554659 2 122 theme conserved 436:444 arg1 determinant 585:595 a novel determinant 577:595 a novel determinant of macrophage tropism 577:617 Here, we identify a highly conserved N-linked glycosylation site (N173 in SIV, corresponding to N160 in HIV) in the V2 region of the SIV envelope glycoprotein (Env) as a novel determinant of macrophage tropism and characterize mechanisms underlying this phenotype. 24554659 3 123 gly glycosylation 691:703 arg2 site 705:708 the N173 glycosylation site 682:708 the N173 glycosylation site in the non-macrophage-tropic SIVmac239 682:747 Loss of the N173 glycosylation site in the non-macrophage-tropic SIVmac239 by introducing an N173Q mutation enhanced viral replication and multinucleated giant cell formation upon infection of rhesus macrophages, while the addition of N173 to SIVmac251 had the opposite effect. 24554659 0 124 theme glycosylation 29:41 arg1 site 43:46 a conserved N-linked glycosylation site 8:46 a conserved N-linked glycosylation site 8:46 Loss of a conserved N-linked glycosylation site in the simian immunodeficiency virus envelope glycoprotein V2 region enhances macrophage tropism by increasing CD4-independent cell-to-cell transmission. 24554659 16 125 theme efficient 2635:2643 arg1 mode 2645:2648 this efficient mode 2630:2648 this efficient mode of virus transmission 2630:2670 Together, these findings suggest that this efficient mode of virus transmission may facilitate the escape of macrophage-tropic viruses from neutralizing antibodies while promoting spreading infection by these viruses to cells expressing little or no CD4 in vivo. 24554659 10 126 theme N173 1679:1682 arg1 site 1707:1710 the N173 N-linked glycosylation site 1675:1710 the N173 N-linked glycosylation site 1675:1710 These findings suggest that the loss of the N173 N-linked glycosylation site increases SIVmac239 replication in macrophages by enhancing CD4-independent cell-to-cell virus transmission through CCR5-mediated fusion. 24554659 5 127 from cells 1159:1163 arg1 infections 1181:1190 single-round infections 1168:1190 single-round infections 1168:1190 SIVmac239 with N173Q mediated CD4-independent cell-cell fusion but could not infect CD4-negative cells in single-round infections. 24554659 4 128 theme cell-to-cell 1010:1021 arg1 transmission 1023:1034 CD4-independent cell-to-cell transmission 994:1034 CD4-independent cell-to-cell transmission to CCR5-expressing cells 994:1059 The removal of N173 in SIVmac239 enhanced CD4-independent cell-to-cell transmission to CCR5-expressing cells. 24554659 8 129 theme SIVmac239 1465:1473 arg1 sensitivity 1450:1460 the neutralization sensitivity 1431:1460 the neutralization sensitivity of SIVmac239 1431:1473 N173 decreased the neutralization sensitivity of SIVmac251 but had no effect on the neutralization sensitivity of SIVmac239. 24554659 10 130 theme cell-to-cell 1788:1799 arg1 transmission 1807:1818 CD4-independent cell-to-cell virus transmission 1772:1818 CD4-independent cell-to-cell virus transmission 1772:1818 These findings suggest that the loss of the N173 N-linked glycosylation site increases SIVmac239 replication in macrophages by enhancing CD4-independent cell-to-cell virus transmission through CCR5-mediated fusion. 24554659 16 131 theme transmission 2659:2670 arg1 mode 2645:2648 this efficient mode 2630:2648 this efficient mode of virus transmission 2630:2670 Together, these findings suggest that this efficient mode of virus transmission may facilitate the escape of macrophage-tropic viruses from neutralizing antibodies while promoting spreading infection by these viruses to cells expressing little or no CD4 in vivo. 24554659 2 132 gly glycosylation 455:467 arg2 determinant 585:595 a novel determinant 577:595 a novel determinant of macrophage tropism 577:617 Here, we identify a highly conserved N-linked glycosylation site (N173 in SIV, corresponding to N160 in HIV) in the V2 region of the SIV envelope glycoprotein (Env) as a novel determinant of macrophage tropism and characterize mechanisms underlying this phenotype. 24554659 2 132 gly glycosylation 455:467 arg2 site 469:472 a highly conserved N-linked glycosylation site 427:472 a highly conserved N-linked glycosylation site (N173 in SIV, corresponding to N160 in HIV) in the V2 region of the SIV envelope glycoprotein (Env) 427:572 Here, we identify a highly conserved N-linked glycosylation site (N173 in SIV, corresponding to N160 in HIV) in the V2 region of the SIV envelope glycoprotein (Env) as a novel determinant of macrophage tropism and characterize mechanisms underlying this phenotype. 24554659 1 133 theme immunodeficiency 248:263 arg1 virus 265:269 simian immunodeficiency virus 241:269 simian immunodeficiency virus (SIV) 241:275 Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) strains differ in their capacity to replicate in macrophages, but mechanisms underlying these differences are not fully understood. 24554659 1 133 theme immunodeficiency 248:263 arg1 SIV 272:274 SIV 272:274 SIV 272:274 Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) strains differ in their capacity to replicate in macrophages, but mechanisms underlying these differences are not fully understood. 24554659 10 134 from replication 1732:1742 arg1 macrophages 1747:1757 macrophages 1747:1757 macrophages 1747:1757 These findings suggest that the loss of the N173 N-linked glycosylation site increases SIVmac239 replication in macrophages by enhancing CD4-independent cell-to-cell virus transmission through CCR5-mediated fusion. 24554659 10 135 theme CCR5-mediated 1828:1840 arg1 fusion 1842:1847 CCR5-mediated fusion 1828:1847 CCR5-mediated fusion 1828:1847 These findings suggest that the loss of the N173 N-linked glycosylation site increases SIVmac239 replication in macrophages by enhancing CD4-independent cell-to-cell virus transmission through CCR5-mediated fusion. 26011979 2 0 theme related 324:330 arg1 illness 332:338 anaemia related illness 316:338 anaemia related illness 316:338 It is a 166 amino acid protein having 3 N-glycosylation and one O-linked glycosylation sites, and is used to treat anaemia related illness. 26011979 2 1 contain having 232:237 arg2 N-glycosylation 241:255 3 N-glycosylation and one O-linked glycosylation sites 239:292 N-glycosylation 241:255 It is a 166 amino acid protein having 3 N-glycosylation and one O-linked glycosylation sites, and is used to treat anaemia related illness. 26011979 2 1 contain having 232:237 arg1 It 201:202 It 201:202 It 201:202 It is a 166 amino acid protein having 3 N-glycosylation and one O-linked glycosylation sites, and is used to treat anaemia related illness. 26011979 2 1 contain having 232:237 arg2 sites 288:292 3 N-glycosylation and one O-linked glycosylation sites 239:292 sites 288:292 It is a 166 amino acid protein having 3 N-glycosylation and one O-linked glycosylation sites, and is used to treat anaemia related illness. 26011979 2 1 contain having 232:237 arg1 protein 224:230 a 166 amino acid protein 207:230 a 166 amino acid protein having 3 N-glycosylation and one O-linked glycosylation sites 207:292 It is a 166 amino acid protein having 3 N-glycosylation and one O-linked glycosylation sites, and is used to treat anaemia related illness. 26011979 2 2 gly glycosylation 274:286 arg2 sites 288:292 3 N-glycosylation and one O-linked glycosylation sites 239:292 sites 288:292 It is a 166 amino acid protein having 3 N-glycosylation and one O-linked glycosylation sites, and is used to treat anaemia related illness. 26011979 2 2 gly glycosylation 274:286 arg2 one 261:263 one 261:263 one 261:263 It is a 166 amino acid protein having 3 N-glycosylation and one O-linked glycosylation sites, and is used to treat anaemia related illness. 26011979 3 3 with glycosylation 467:479 arg1 levels 502:507 low levels 498:507 low levels of fully glycosylated active rEPO 498:541 Though human recombinant erythropoietin (rEPO) is produced in CHO cells, the loss in quality control is 80% due to incomplete glycosylation of the rEPO with low levels of fully glycosylated active rEPO. 26011979 2 4 theme O-linked 265:272 arg1 sites 288:292 3 N-glycosylation and one O-linked glycosylation sites 239:292 sites 288:292 It is a 166 amino acid protein having 3 N-glycosylation and one O-linked glycosylation sites, and is used to treat anaemia related illness. 26011979 7 5 theme biological 1265:1274 arg1 activity 1276:1283 a higher in vivo biological activity 1248:1283 a higher in vivo biological activity due to its high molecular weight of 40 kD 1248:1325 The GPI anchor can be removed during the purification process to yield a therapeutically relevant recombinant erythropoietin molecule cells with a higher in vivo biological activity due to its high molecular weight of 40 kD. 26011979 4 6 theme glycosylated 601:612 arg1 rEPO 620:623 fully glycosylated human rEPO 595:623 fully glycosylated human rEPO 595:623 Here, we describe the expression from CHO cells of fully glycosylated human rEPO when expressed as a GPI anchored molecule (rEPO-g). 26011979 1 7 theme cell 188:191 arg1 levels 193:198 the blood cell levels 178:198 the blood cell levels 178:198 Erythropoietin is a glycohormone involved in the regulation of the blood cell levels. 26011979 6 8 theme recombinant 1082:1092 arg1 protein 1094:1100 the expressed recombinant protein 1068:1100 the expressed recombinant protein 1068:1100 The western blot using specific monoclonal antibody is the available biochemical technique to prove the presence of homogeneity in the expressed recombinant protein. 26011979 8 9 from report 1355:1360 arg1 production 1369:1378 the production 1365:1378 the production of a homogenous and completely glycosylated human rEPO from CHO cells for efficient therapy 1365:1470 This is possibly the first report on the production of a homogenous and completely glycosylated human rEPO from CHO cells for efficient therapy. 26011979 7 10 theme kD 1324:1325 arg1 weight 1311:1316 its high molecular weight 1292:1316 its high molecular weight of 40 kD 1292:1325 The GPI anchor can be removed during the purification process to yield a therapeutically relevant recombinant erythropoietin molecule cells with a higher in vivo biological activity due to its high molecular weight of 40 kD. 26011979 4 11 theme CHO 582:584 arg1 cells 586:590 CHO cells 582:590 CHO cells of fully glycosylated human rEPO 582:623 Here, we describe the expression from CHO cells of fully glycosylated human rEPO when expressed as a GPI anchored molecule (rEPO-g). 26011979 0 12 theme anchored 18:25 arg1 erythropoietin 45:58 GPI anchored human recombinant erythropoietin 14:58 GPI anchored human recombinant erythropoietin 14:58 Expression of GPI anchored human recombinant erythropoietin in CHO cells is devoid of glycosylation heterogeneity. 26011979 5 13 theme 42 775:776 arg1 kD 778:779 kD 778:779 kD 778:779 The results demonstrated the production of a homogenous completely glycosylated human rEPO-g as a 42 kD band without any low molecular weight glycoform variants as shown by affinity chromatography followed by SDS-PAGE and anti-human EPO specific western blot. 26011979 3 14 theme active 531:536 arg1 rEPO 538:541 fully glycosylated active rEPO 512:541 fully glycosylated active rEPO 512:541 Though human recombinant erythropoietin (rEPO) is produced in CHO cells, the loss in quality control is 80% due to incomplete glycosylation of the rEPO with low levels of fully glycosylated active rEPO. 26011979 7 15 theme molecular 1301:1309 arg1 weight 1311:1316 its high molecular weight 1292:1316 its high molecular weight of 40 kD 1292:1325 The GPI anchor can be removed during the purification process to yield a therapeutically relevant recombinant erythropoietin molecule cells with a higher in vivo biological activity due to its high molecular weight of 40 kD. 26011979 4 16 theme anchored 649:656 arg1 rEPO-g 668:673 rEPO-g 668:673 rEPO-g 668:673 Here, we describe the expression from CHO cells of fully glycosylated human rEPO when expressed as a GPI anchored molecule (rEPO-g). 26011979 4 16 theme anchored 649:656 arg1 molecule 658:665 a GPI anchored molecule 643:665 a GPI anchored molecule (rEPO-g) 643:674 Here, we describe the expression from CHO cells of fully glycosylated human rEPO when expressed as a GPI anchored molecule (rEPO-g). 26011979 3 17 theme rEPO 488:491 arg1 glycosylation 467:479 incomplete glycosylation 456:479 incomplete glycosylation of the rEPO with low levels of fully glycosylated active rEPO 456:541 Though human recombinant erythropoietin (rEPO) is produced in CHO cells, the loss in quality control is 80% due to incomplete glycosylation of the rEPO with low levels of fully glycosylated active rEPO. 26011979 8 18 theme glycosylated 1411:1422 arg1 rEPO 1430:1433 a homogenous and completely glycosylated human rEPO 1383:1433 a homogenous and completely glycosylated human rEPO from CHO cells for efficient therapy 1383:1470 This is possibly the first report on the production of a homogenous and completely glycosylated human rEPO from CHO cells for efficient therapy. 26011979 4 19 theme rEPO 620:623 arg1 cells 586:590 CHO cells 582:590 CHO cells of fully glycosylated human rEPO 582:623 Here, we describe the expression from CHO cells of fully glycosylated human rEPO when expressed as a GPI anchored molecule (rEPO-g). 26011979 0 20 theme CHO 63:65 arg1 cells 67:71 CHO cells 63:71 CHO cells 63:71 Expression of GPI anchored human recombinant erythropoietin in CHO cells is devoid of glycosylation heterogeneity. 26011979 0 21 theme GPI 14:16 arg1 erythropoietin 45:58 GPI anchored human recombinant erythropoietin 14:58 GPI anchored human recombinant erythropoietin 14:58 Expression of GPI anchored human recombinant erythropoietin in CHO cells is devoid of glycosylation heterogeneity. 26011979 5 22 theme molecular 802:810 arg1 variants 829:836 any low molecular weight glycoform variants 794:836 any low molecular weight glycoform variants as shown by affinity chromatography followed by SDS-PAGE and anti-human EPO specific western blot 794:934 The results demonstrated the production of a homogenous completely glycosylated human rEPO-g as a 42 kD band without any low molecular weight glycoform variants as shown by affinity chromatography followed by SDS-PAGE and anti-human EPO specific western blot. 26011979 8 23 theme rEPO 1430:1433 arg1 production 1369:1378 the production 1365:1378 the production of a homogenous and completely glycosylated human rEPO from CHO cells for efficient therapy 1365:1470 This is possibly the first report on the production of a homogenous and completely glycosylated human rEPO from CHO cells for efficient therapy. 26011979 4 24 gly glycosylated 601:612 arg1 rEPO 620:623 fully glycosylated human rEPO 595:623 fully glycosylated human rEPO 595:623 Here, we describe the expression from CHO cells of fully glycosylated human rEPO when expressed as a GPI anchored molecule (rEPO-g). 26011979 8 25 from production 1369:1378 arg1 cells 1444:1448 CHO cells 1440:1448 CHO cells 1440:1448 This is possibly the first report on the production of a homogenous and completely glycosylated human rEPO from CHO cells for efficient therapy. 26011979 5 26 theme glycoform 819:827 arg1 variants 829:836 any low molecular weight glycoform variants 794:836 any low molecular weight glycoform variants as shown by affinity chromatography followed by SDS-PAGE and anti-human EPO specific western blot 794:934 The results demonstrated the production of a homogenous completely glycosylated human rEPO-g as a 42 kD band without any low molecular weight glycoform variants as shown by affinity chromatography followed by SDS-PAGE and anti-human EPO specific western blot. 26011979 8 27 theme CHO 1440:1442 arg1 cells 1444:1448 CHO cells 1440:1448 CHO cells 1440:1448 This is possibly the first report on the production of a homogenous and completely glycosylated human rEPO from CHO cells for efficient therapy. 26011979 3 28 gly glycosylation 467:479 arg1 rEPO 488:491 the rEPO 484:491 the rEPO 484:491 Though human recombinant erythropoietin (rEPO) is produced in CHO cells, the loss in quality control is 80% due to incomplete glycosylation of the rEPO with low levels of fully glycosylated active rEPO. 26011979 5 29 dep variants 829:836 arg1 shown 841:845 shown 841:845 shown by affinity chromatography followed by SDS-PAGE and anti-human EPO specific western blot 841:934 The results demonstrated the production of a homogenous completely glycosylated human rEPO-g as a 42 kD band without any low molecular weight glycoform variants as shown by affinity chromatography followed by SDS-PAGE and anti-human EPO specific western blot. 26011979 0 30 theme heterogeneity 100:112 arg1 devoid 76:81 devoid 76:81 devoid 76:81 Expression of GPI anchored human recombinant erythropoietin in CHO cells is devoid of glycosylation heterogeneity. 26011979 5 31 theme EPO 910:912 arg1 blot 931:934 anti-human EPO specific western blot 899:934 anti-human EPO specific western blot 899:934 The results demonstrated the production of a homogenous completely glycosylated human rEPO-g as a 42 kD band without any low molecular weight glycoform variants as shown by affinity chromatography followed by SDS-PAGE and anti-human EPO specific western blot. 26011979 6 32 dep available 996:1004 arg1 biochemical 1006:1016 biochemical 1006:1016 biochemical 1006:1016 The western blot using specific monoclonal antibody is the available biochemical technique to prove the presence of homogeneity in the expressed recombinant protein. 26011979 3 33 theme human 348:352 arg1 erythropoietin 366:379 human recombinant erythropoietin 348:379 human recombinant erythropoietin (rEPO) 348:386 Though human recombinant erythropoietin (rEPO) is produced in CHO cells, the loss in quality control is 80% due to incomplete glycosylation of the rEPO with low levels of fully glycosylated active rEPO. 26011979 3 33 theme human 348:352 arg1 rEPO 382:385 rEPO 382:385 rEPO 382:385 Though human recombinant erythropoietin (rEPO) is produced in CHO cells, the loss in quality control is 80% due to incomplete glycosylation of the rEPO with low levels of fully glycosylated active rEPO. 26011979 7 34 theme GPI 1107:1109 arg1 anchor 1111:1116 The GPI anchor 1103:1116 The GPI anchor 1103:1116 The GPI anchor can be removed during the purification process to yield a therapeutically relevant recombinant erythropoietin molecule cells with a higher in vivo biological activity due to its high molecular weight of 40 kD. 26011979 6 35 attach presence 1041:1048 arg1 protein 1094:1100 the expressed recombinant protein 1068:1100 the expressed recombinant protein 1068:1100 The western blot using specific monoclonal antibody is the available biochemical technique to prove the presence of homogeneity in the expressed recombinant protein. 26011979 6 35 attach presence 1041:1048 arg2 homogeneity 1053:1063 homogeneity 1053:1063 homogeneity 1053:1063 The western blot using specific monoclonal antibody is the available biochemical technique to prove the presence of homogeneity in the expressed recombinant protein. 26011979 0 36 theme human 27:31 arg1 erythropoietin 45:58 GPI anchored human recombinant erythropoietin 14:58 GPI anchored human recombinant erythropoietin 14:58 Expression of GPI anchored human recombinant erythropoietin in CHO cells is devoid of glycosylation heterogeneity. 26011979 7 37 theme higher 1250:1255 arg1 activity 1276:1283 a higher in vivo biological activity 1248:1283 a higher in vivo biological activity due to its high molecular weight of 40 kD 1248:1325 The GPI anchor can be removed during the purification process to yield a therapeutically relevant recombinant erythropoietin molecule cells with a higher in vivo biological activity due to its high molecular weight of 40 kD. 26011979 3 38 from loss 418:421 arg1 control 434:440 quality control 426:440 quality control 426:440 Though human recombinant erythropoietin (rEPO) is produced in CHO cells, the loss in quality control is 80% due to incomplete glycosylation of the rEPO with low levels of fully glycosylated active rEPO. 26011979 0 39 theme erythropoietin 45:58 arg1 Expression 0:9 Expression 0:9 Expression of GPI anchored human recombinant erythropoietin in CHO cells 0:71 Expression of GPI anchored human recombinant erythropoietin in CHO cells is devoid of glycosylation heterogeneity. 26011979 5 40 theme western 923:929 arg1 blot 931:934 anti-human EPO specific western blot 899:934 anti-human EPO specific western blot 899:934 The results demonstrated the production of a homogenous completely glycosylated human rEPO-g as a 42 kD band without any low molecular weight glycoform variants as shown by affinity chromatography followed by SDS-PAGE and anti-human EPO specific western blot. 26011979 7 41 theme molecule 1228:1235 arg1 cells 1237:1241 a therapeutically relevant recombinant erythropoietin molecule cells 1174:1241 a therapeutically relevant recombinant erythropoietin molecule cells 1174:1241 The GPI anchor can be removed during the purification process to yield a therapeutically relevant recombinant erythropoietin molecule cells with a higher in vivo biological activity due to its high molecular weight of 40 kD. 26011979 6 42 theme specific 960:967 arg1 antibody 980:987 specific monoclonal antibody 960:987 specific monoclonal antibody 960:987 The western blot using specific monoclonal antibody is the available biochemical technique to prove the presence of homogeneity in the expressed recombinant protein. 26011979 3 43 theme incomplete 456:465 arg1 glycosylation 467:479 incomplete glycosylation 456:479 incomplete glycosylation of the rEPO with low levels of fully glycosylated active rEPO 456:541 Though human recombinant erythropoietin (rEPO) is produced in CHO cells, the loss in quality control is 80% due to incomplete glycosylation of the rEPO with low levels of fully glycosylated active rEPO. 26011979 7 44 theme recombinant 1201:1211 arg1 molecule 1228:1235 a therapeutically relevant recombinant erythropoietin molecule 1174:1235 a therapeutically relevant recombinant erythropoietin molecule cells 1174:1241 The GPI anchor can be removed during the purification process to yield a therapeutically relevant recombinant erythropoietin molecule cells with a higher in vivo biological activity due to its high molecular weight of 40 kD. 26011979 2 45 theme glycosylation 274:286 arg1 sites 288:292 3 N-glycosylation and one O-linked glycosylation sites 239:292 sites 288:292 It is a 166 amino acid protein having 3 N-glycosylation and one O-linked glycosylation sites, and is used to treat anaemia related illness. 26011979 5 46 theme kD 778:779 arg1 band 781:784 a 42 kD band 773:784 a 42 kD band without any low molecular weight glycoform variants as shown by affinity chromatography followed by SDS-PAGE and anti-human EPO specific western blot 773:934 The results demonstrated the production of a homogenous completely glycosylated human rEPO-g as a 42 kD band without any low molecular weight glycoform variants as shown by affinity chromatography followed by SDS-PAGE and anti-human EPO specific western blot. 26011979 5 46 theme kD 778:779 arg1 production 706:715 the production 702:715 the production of a homogenous completely glycosylated human rEPO-g 702:768 The results demonstrated the production of a homogenous completely glycosylated human rEPO-g as a 42 kD band without any low molecular weight glycoform variants as shown by affinity chromatography followed by SDS-PAGE and anti-human EPO specific western blot. 26011979 4 47 from cells 586:590 arg1 expression 566:575 the expression 562:575 the expression from CHO cells of fully glycosylated human rEPO 562:623 Here, we describe the expression from CHO cells of fully glycosylated human rEPO when expressed as a GPI anchored molecule (rEPO-g). 26011979 1 48 theme blood 182:186 arg1 levels 193:198 the blood cell levels 178:198 the blood cell levels 178:198 Erythropoietin is a glycohormone involved in the regulation of the blood cell levels. 26011979 3 49 theme low 498:500 arg1 levels 502:507 low levels 498:507 low levels of fully glycosylated active rEPO 498:541 Though human recombinant erythropoietin (rEPO) is produced in CHO cells, the loss in quality control is 80% due to incomplete glycosylation of the rEPO with low levels of fully glycosylated active rEPO. 26011979 1 50 theme levels 193:198 arg1 regulation 164:173 the regulation 160:173 the regulation of the blood cell levels 160:198 Erythropoietin is a glycohormone involved in the regulation of the blood cell levels. 26011979 6 51 theme expressed 1072:1080 arg1 protein 1094:1100 the expressed recombinant protein 1068:1100 the expressed recombinant protein 1068:1100 The western blot using specific monoclonal antibody is the available biochemical technique to prove the presence of homogeneity in the expressed recombinant protein. 26011979 2 52 link O-linked 265:272 arg1 sites 288:292 3 N-glycosylation and one O-linked glycosylation sites 239:292 sites 288:292 It is a 166 amino acid protein having 3 N-glycosylation and one O-linked glycosylation sites, and is used to treat anaemia related illness. 26011979 3 53 theme rEPO 538:541 arg1 levels 502:507 low levels 498:507 low levels of fully glycosylated active rEPO 498:541 Though human recombinant erythropoietin (rEPO) is produced in CHO cells, the loss in quality control is 80% due to incomplete glycosylation of the rEPO with low levels of fully glycosylated active rEPO. 26011979 8 54 gly glycosylated 1411:1422 arg1 rEPO 1430:1433 a homogenous and completely glycosylated human rEPO 1383:1433 a homogenous and completely glycosylated human rEPO from CHO cells for efficient therapy 1383:1470 This is possibly the first report on the production of a homogenous and completely glycosylated human rEPO from CHO cells for efficient therapy. 26011979 8 55 theme homogenous 1385:1394 arg1 rEPO 1430:1433 a homogenous and completely glycosylated human rEPO 1383:1433 a homogenous and completely glycosylated human rEPO from CHO cells for efficient therapy 1383:1470 This is possibly the first report on the production of a homogenous and completely glycosylated human rEPO from CHO cells for efficient therapy. 26011979 3 56 gly glycosylated 518:529 arg1 rEPO 538:541 fully glycosylated active rEPO 512:541 fully glycosylated active rEPO 512:541 Though human recombinant erythropoietin (rEPO) is produced in CHO cells, the loss in quality control is 80% due to incomplete glycosylation of the rEPO with low levels of fully glycosylated active rEPO. 26011979 5 57 theme human 757:761 arg1 rEPO-g 763:768 a homogenous completely glycosylated human rEPO-g 720:768 a homogenous completely glycosylated human rEPO-g 720:768 The results demonstrated the production of a homogenous completely glycosylated human rEPO-g as a 42 kD band without any low molecular weight glycoform variants as shown by affinity chromatography followed by SDS-PAGE and anti-human EPO specific western blot. 26011979 3 58 theme glycosylated 518:529 arg1 rEPO 538:541 fully glycosylated active rEPO 512:541 fully glycosylated active rEPO 512:541 Though human recombinant erythropoietin (rEPO) is produced in CHO cells, the loss in quality control is 80% due to incomplete glycosylation of the rEPO with low levels of fully glycosylated active rEPO. 26011979 0 59 from Expression 0:9 arg1 cells 67:71 CHO cells 63:71 CHO cells 63:71 Expression of GPI anchored human recombinant erythropoietin in CHO cells is devoid of glycosylation heterogeneity. 26011979 8 60 theme human 1424:1428 arg1 rEPO 1430:1433 a homogenous and completely glycosylated human rEPO 1383:1433 a homogenous and completely glycosylated human rEPO from CHO cells for efficient therapy 1383:1470 This is possibly the first report on the production of a homogenous and completely glycosylated human rEPO from CHO cells for efficient therapy. 26011979 4 61 theme GPI 645:647 arg1 rEPO-g 668:673 rEPO-g 668:673 rEPO-g 668:673 Here, we describe the expression from CHO cells of fully glycosylated human rEPO when expressed as a GPI anchored molecule (rEPO-g). 26011979 4 61 theme GPI 645:647 arg1 molecule 658:665 a GPI anchored molecule 643:665 a GPI anchored molecule (rEPO-g) 643:674 Here, we describe the expression from CHO cells of fully glycosylated human rEPO when expressed as a GPI anchored molecule (rEPO-g). 26011979 7 62 theme erythropoietin 1213:1226 arg1 molecule 1228:1235 a therapeutically relevant recombinant erythropoietin molecule 1174:1235 a therapeutically relevant recombinant erythropoietin molecule cells 1174:1241 The GPI anchor can be removed during the purification process to yield a therapeutically relevant recombinant erythropoietin molecule cells with a higher in vivo biological activity due to its high molecular weight of 40 kD. 26011979 5 63 theme rEPO-g 763:768 arg1 band 781:784 a 42 kD band 773:784 a 42 kD band without any low molecular weight glycoform variants as shown by affinity chromatography followed by SDS-PAGE and anti-human EPO specific western blot 773:934 The results demonstrated the production of a homogenous completely glycosylated human rEPO-g as a 42 kD band without any low molecular weight glycoform variants as shown by affinity chromatography followed by SDS-PAGE and anti-human EPO specific western blot. 26011979 5 63 theme rEPO-g 763:768 arg1 production 706:715 the production 702:715 the production of a homogenous completely glycosylated human rEPO-g 702:768 The results demonstrated the production of a homogenous completely glycosylated human rEPO-g as a 42 kD band without any low molecular weight glycoform variants as shown by affinity chromatography followed by SDS-PAGE and anti-human EPO specific western blot. 26011979 5 64 theme low 798:800 arg1 variants 829:836 any low molecular weight glycoform variants 794:836 any low molecular weight glycoform variants as shown by affinity chromatography followed by SDS-PAGE and anti-human EPO specific western blot 794:934 The results demonstrated the production of a homogenous completely glycosylated human rEPO-g as a 42 kD band without any low molecular weight glycoform variants as shown by affinity chromatography followed by SDS-PAGE and anti-human EPO specific western blot. 26011979 6 65 theme western 941:947 arg1 blot 949:952 The western blot 937:952 The western blot using specific monoclonal antibody 937:987 The western blot using specific monoclonal antibody is the available biochemical technique to prove the presence of homogeneity in the expressed recombinant protein. 26011979 6 65 theme western 941:947 arg1 technique 1018:1026 the available biochemical technique 992:1026 the available biochemical technique to prove the presence of homogeneity in the expressed recombinant protein 992:1100 The western blot using specific monoclonal antibody is the available biochemical technique to prove the presence of homogeneity in the expressed recombinant protein. 26011979 7 66 theme high 1296:1299 arg1 weight 1311:1316 its high molecular weight 1292:1316 its high molecular weight of 40 kD 1292:1325 The GPI anchor can be removed during the purification process to yield a therapeutically relevant recombinant erythropoietin molecule cells with a higher in vivo biological activity due to its high molecular weight of 40 kD. 26011979 4 67 theme human 614:618 arg1 rEPO 620:623 fully glycosylated human rEPO 595:623 fully glycosylated human rEPO 595:623 Here, we describe the expression from CHO cells of fully glycosylated human rEPO when expressed as a GPI anchored molecule (rEPO-g). 26011979 7 68 theme purification 1144:1155 arg1 process 1157:1163 the purification process 1140:1163 the purification process 1140:1163 The GPI anchor can be removed during the purification process to yield a therapeutically relevant recombinant erythropoietin molecule cells with a higher in vivo biological activity due to its high molecular weight of 40 kD. 26011979 5 69 theme weight 812:817 arg1 variants 829:836 any low molecular weight glycoform variants 794:836 any low molecular weight glycoform variants as shown by affinity chromatography followed by SDS-PAGE and anti-human EPO specific western blot 794:934 The results demonstrated the production of a homogenous completely glycosylated human rEPO-g as a 42 kD band without any low molecular weight glycoform variants as shown by affinity chromatography followed by SDS-PAGE and anti-human EPO specific western blot. 26011979 0 70 theme glycosylation 86:98 arg1 heterogeneity 100:112 glycosylation heterogeneity 86:112 glycosylation heterogeneity 86:112 Expression of GPI anchored human recombinant erythropoietin in CHO cells is devoid of glycosylation heterogeneity. 26011979 7 71 dep higher 1250:1255 arg1 in 1257:1258 in 1257:1258 in 1257:1258 The GPI anchor can be removed during the purification process to yield a therapeutically relevant recombinant erythropoietin molecule cells with a higher in vivo biological activity due to its high molecular weight of 40 kD. 26011979 8 72 theme efficient 1454:1462 arg1 therapy 1464:1470 efficient therapy 1454:1470 efficient therapy 1454:1470 This is possibly the first report on the production of a homogenous and completely glycosylated human rEPO from CHO cells for efficient therapy. 26011979 5 73 theme anti-human 899:908 arg1 blot 931:934 anti-human EPO specific western blot 899:934 anti-human EPO specific western blot 899:934 The results demonstrated the production of a homogenous completely glycosylated human rEPO-g as a 42 kD band without any low molecular weight glycoform variants as shown by affinity chromatography followed by SDS-PAGE and anti-human EPO specific western blot. 26011979 7 74 theme due 1285:1287 arg1 activity 1276:1283 a higher in vivo biological activity 1248:1283 a higher in vivo biological activity due to its high molecular weight of 40 kD 1248:1325 The GPI anchor can be removed during the purification process to yield a therapeutically relevant recombinant erythropoietin molecule cells with a higher in vivo biological activity due to its high molecular weight of 40 kD. 26011979 2 75 used used 302:305 arg2 It 201:202 It 201:202 It 201:202 It is a 166 amino acid protein having 3 N-glycosylation and one O-linked glycosylation sites, and is used to treat anaemia related illness. 26011979 2 75 used used 302:305 arg2 protein 224:230 a 166 amino acid protein 207:230 a 166 amino acid protein having 3 N-glycosylation and one O-linked glycosylation sites 207:292 It is a 166 amino acid protein having 3 N-glycosylation and one O-linked glycosylation sites, and is used to treat anaemia related illness. 26011979 5 76 theme homogenous 722:731 arg1 rEPO-g 763:768 a homogenous completely glycosylated human rEPO-g 720:768 a homogenous completely glycosylated human rEPO-g 720:768 The results demonstrated the production of a homogenous completely glycosylated human rEPO-g as a 42 kD band without any low molecular weight glycoform variants as shown by affinity chromatography followed by SDS-PAGE and anti-human EPO specific western blot. 26011979 5 77 theme affinity 850:857 arg1 chromatography 859:872 affinity chromatography 850:872 affinity chromatography followed by SDS-PAGE and anti-human EPO specific western blot 850:934 The results demonstrated the production of a homogenous completely glycosylated human rEPO-g as a 42 kD band without any low molecular weight glycoform variants as shown by affinity chromatography followed by SDS-PAGE and anti-human EPO specific western blot. 26011979 6 78 theme available 996:1004 arg1 blot 949:952 The western blot 937:952 The western blot using specific monoclonal antibody 937:987 The western blot using specific monoclonal antibody is the available biochemical technique to prove the presence of homogeneity in the expressed recombinant protein. 26011979 6 78 theme available 996:1004 arg1 technique 1018:1026 the available biochemical technique 992:1026 the available biochemical technique to prove the presence of homogeneity in the expressed recombinant protein 992:1100 The western blot using specific monoclonal antibody is the available biochemical technique to prove the presence of homogeneity in the expressed recombinant protein. 26011979 3 79 theme CHO 403:405 arg1 cells 407:411 CHO cells 403:411 CHO cells 403:411 Though human recombinant erythropoietin (rEPO) is produced in CHO cells, the loss in quality control is 80% due to incomplete glycosylation of the rEPO with low levels of fully glycosylated active rEPO. 26011979 5 80 theme glycosylated 744:755 arg1 rEPO-g 763:768 a homogenous completely glycosylated human rEPO-g 720:768 a homogenous completely glycosylated human rEPO-g 720:768 The results demonstrated the production of a homogenous completely glycosylated human rEPO-g as a 42 kD band without any low molecular weight glycoform variants as shown by affinity chromatography followed by SDS-PAGE and anti-human EPO specific western blot. 26011979 2 81 theme acid 219:222 arg1 It 201:202 It 201:202 It 201:202 It is a 166 amino acid protein having 3 N-glycosylation and one O-linked glycosylation sites, and is used to treat anaemia related illness. 26011979 2 81 theme acid 219:222 arg1 protein 224:230 a 166 amino acid protein 207:230 a 166 amino acid protein having 3 N-glycosylation and one O-linked glycosylation sites 207:292 It is a 166 amino acid protein having 3 N-glycosylation and one O-linked glycosylation sites, and is used to treat anaemia related illness. 26011979 3 82 theme recombinant 354:364 arg1 erythropoietin 366:379 human recombinant erythropoietin 348:379 human recombinant erythropoietin (rEPO) 348:386 Though human recombinant erythropoietin (rEPO) is produced in CHO cells, the loss in quality control is 80% due to incomplete glycosylation of the rEPO with low levels of fully glycosylated active rEPO. 26011979 3 82 theme recombinant 354:364 arg1 rEPO 382:385 rEPO 382:385 rEPO 382:385 Though human recombinant erythropoietin (rEPO) is produced in CHO cells, the loss in quality control is 80% due to incomplete glycosylation of the rEPO with low levels of fully glycosylated active rEPO. 26011979 3 83 theme quality 426:432 arg1 control 434:440 quality control 426:440 quality control 426:440 Though human recombinant erythropoietin (rEPO) is produced in CHO cells, the loss in quality control is 80% due to incomplete glycosylation of the rEPO with low levels of fully glycosylated active rEPO. 26011979 0 84 theme recombinant 33:43 arg1 erythropoietin 45:58 GPI anchored human recombinant erythropoietin 14:58 GPI anchored human recombinant erythropoietin 14:58 Expression of GPI anchored human recombinant erythropoietin in CHO cells is devoid of glycosylation heterogeneity. 26011979 6 85 theme monoclonal 969:978 arg1 antibody 980:987 specific monoclonal antibody 960:987 specific monoclonal antibody 960:987 The western blot using specific monoclonal antibody is the available biochemical technique to prove the presence of homogeneity in the expressed recombinant protein. 26011979 5 86 gly glycosylated 744:755 arg1 rEPO-g 763:768 a homogenous completely glycosylated human rEPO-g 720:768 a homogenous completely glycosylated human rEPO-g 720:768 The results demonstrated the production of a homogenous completely glycosylated human rEPO-g as a 42 kD band without any low molecular weight glycoform variants as shown by affinity chromatography followed by SDS-PAGE and anti-human EPO specific western blot. 26011979 5 87 theme specific 914:921 arg1 blot 931:934 anti-human EPO specific western blot 899:934 anti-human EPO specific western blot 899:934 The results demonstrated the production of a homogenous completely glycosylated human rEPO-g as a 42 kD band without any low molecular weight glycoform variants as shown by affinity chromatography followed by SDS-PAGE and anti-human EPO specific western blot. 26011979 2 88 theme amino 213:217 arg1 It 201:202 It 201:202 It 201:202 It is a 166 amino acid protein having 3 N-glycosylation and one O-linked glycosylation sites, and is used to treat anaemia related illness. 26011979 2 88 theme amino 213:217 arg1 protein 224:230 a 166 amino acid protein 207:230 a 166 amino acid protein having 3 N-glycosylation and one O-linked glycosylation sites 207:292 It is a 166 amino acid protein having 3 N-glycosylation and one O-linked glycosylation sites, and is used to treat anaemia related illness. 26011979 6 89 theme homogeneity 1053:1063 arg1 presence 1041:1048 the presence 1037:1048 the presence of homogeneity in the expressed recombinant protein 1037:1100 The western blot using specific monoclonal antibody is the available biochemical technique to prove the presence of homogeneity in the expressed recombinant protein. 26011979 8 90 theme first 1349:1353 arg1 report 1355:1360 the first report 1345:1360 the first report on the production of a homogenous and completely glycosylated human rEPO from CHO cells for efficient therapy 1345:1470 This is possibly the first report on the production of a homogenous and completely glycosylated human rEPO from CHO cells for efficient therapy. 26011979 8 90 theme first 1349:1353 arg1 This 1328:1331 This 1328:1331 This 1328:1331 This is possibly the first report on the production of a homogenous and completely glycosylated human rEPO from CHO cells for efficient therapy. 26011979 7 91 dep in 1257:1258 arg1 vivo 1260:1263 vivo 1260:1263 vivo 1260:1263 The GPI anchor can be removed during the purification process to yield a therapeutically relevant recombinant erythropoietin molecule cells with a higher in vivo biological activity due to its high molecular weight of 40 kD. 26011979 7 92 theme relevant 1192:1199 arg1 molecule 1228:1235 a therapeutically relevant recombinant erythropoietin molecule 1174:1235 a therapeutically relevant recombinant erythropoietin molecule cells 1174:1241 The GPI anchor can be removed during the purification process to yield a therapeutically relevant recombinant erythropoietin molecule cells with a higher in vivo biological activity due to its high molecular weight of 40 kD. 26011979 6 93 from presence 1041:1048 arg1 protein 1094:1100 the expressed recombinant protein 1068:1100 the expressed recombinant protein 1068:1100 The western blot using specific monoclonal antibody is the available biochemical technique to prove the presence of homogeneity in the expressed recombinant protein. 26011979 8 94 from cells 1444:1448 arg1 production 1369:1378 the production 1365:1378 the production of a homogenous and completely glycosylated human rEPO from CHO cells for efficient therapy 1365:1470 This is possibly the first report on the production of a homogenous and completely glycosylated human rEPO from CHO cells for efficient therapy. 26011979 8 94 from cells 1444:1448 arg1 rEPO 1430:1433 a homogenous and completely glycosylated human rEPO 1383:1433 a homogenous and completely glycosylated human rEPO from CHO cells for efficient therapy 1383:1470 This is possibly the first report on the production of a homogenous and completely glycosylated human rEPO from CHO cells for efficient therapy. 25505062 9 0 theme retroviral 1674:1683 arg1 factor 1697:1702 a host genome-encoded retroviral restriction factor 1652:1702 a host genome-encoded retroviral restriction factor 1652:1702 Overall, we present here the first description of how gammaretroviruses employ posttranslational modification to antagonize and modulate the activity of a host genome-encoded retroviral restriction factor. 25505062 9 1 theme factor 1697:1702 arg1 activity 1640:1647 the activity 1636:1647 the activity of a host genome-encoded retroviral restriction factor 1636:1702 Overall, we present here the first description of how gammaretroviruses employ posttranslational modification to antagonize and modulate the activity of a host genome-encoded retroviral restriction factor. 25505062 4 2 theme glycosylated 585:596 arg1 Gag 603:605 glycosylated Pr80 Gag 585:605 glycosylated Pr80 Gag (gPr80) 585:613 Glycosylated Gag, also called glycosylated Pr80 Gag (gPr80), is a gammaretrovirus genome-encoded protein that inhibits the antiretroviral activity of mouse A3 (mA3). 25505062 4 2 theme glycosylated 585:596 arg1 gPr80 608:612 gPr80 608:612 gPr80 608:612 Glycosylated Gag, also called glycosylated Pr80 Gag (gPr80), is a gammaretrovirus genome-encoded protein that inhibits the antiretroviral activity of mouse A3 (mA3). 25505062 14 3 theme APOBEC3 2426:2432 arg1 proteins 2434:2441 APOBEC3 proteins 2426:2441 APOBEC3 proteins 2426:2441 By carefully controlling the amount of mutations caused by APOBEC3 proteins, gammaretroviruses can find a balance that helps them evolve and persist. 25505062 2 4 theme APOBEC3 281:287 arg1 proteins 294:301 APOBEC3 (A3) proteins 281:301 APOBEC3 (A3) proteins 281:301 Host intrinsic restriction factors, such as APOBEC3 (A3) proteins, are constitutively expressed and dedicated to interfering with the replication cycle of retroviruses. 25505062 0 5 link N-linked 0:7 arg1 glycosylation 9:21 N-linked glycosylation 0:21 N-linked glycosylation 0:21 N-linked glycosylation protects gammaretroviruses against deamination by APOBEC3 proteins. 25505062 4 6 theme genome-encoded 637:650 arg1 protein 652:658 a gammaretrovirus genome-encoded protein 619:658 a gammaretrovirus genome-encoded protein that inhibits the antiretroviral activity of mouse A3 (mA3) 619:718 Glycosylated Gag, also called glycosylated Pr80 Gag (gPr80), is a gammaretrovirus genome-encoded protein that inhibits the antiretroviral activity of mouse A3 (mA3). 25505062 4 6 theme genome-encoded 637:650 arg1 Gag 568:570 Glycosylated Gag 555:570 Glycosylated Gag 555:570 Glycosylated Gag, also called glycosylated Pr80 Gag (gPr80), is a gammaretrovirus genome-encoded protein that inhibits the antiretroviral activity of mouse A3 (mA3). 25505062 3 7 theme virus 514:518 arg1 proteins 545:552 virus genome-encoded accessory proteins 514:552 virus genome-encoded accessory proteins 514:552 To survive, propagate, and persist, retroviruses must counteract these restriction factors, often by way of virus genome-encoded accessory proteins. 25505062 1 8 theme genome 179:184 arg1 instability 186:196 genome instability 179:196 genome instability 179:196 Retroviruses are pathogens with rapid infection cycles that can be a source of disease, genome instability, and tumor development in their hosts. 25505062 1 9 with pathogens 108:116 arg1 source 160:165 a source 158:165 a source of disease, genome instability, and tumor development in their hosts 158:234 Retroviruses are pathogens with rapid infection cycles that can be a source of disease, genome instability, and tumor development in their hosts. 25505062 1 9 with pathogens 108:116 arg1 cycles 139:144 rapid infection cycles 123:144 rapid infection cycles that can be a source of disease, genome instability, and tumor development in their hosts 123:234 Retroviruses are pathogens with rapid infection cycles that can be a source of disease, genome instability, and tumor development in their hosts. 25505062 13 10 theme glycosylated 2176:2187 arg1 Gag 2189:2191 glycosylated Gag 2176:2191 glycosylated Gag 2176:2191 We show that gammaretroviruses expressing an accessory protein called glycosylated Gag, or gPr80, use the host's posttranslational machinery and, more specifically, N-linked glycosylation as a way to modulate their sensitivity to mutations by APOBEC3 proteins. 25505062 2 11 theme A3 290:291 arg1 proteins 294:301 APOBEC3 (A3) proteins 281:301 APOBEC3 (A3) proteins 281:301 Host intrinsic restriction factors, such as APOBEC3 (A3) proteins, are constitutively expressed and dedicated to interfering with the replication cycle of retroviruses. 25505062 13 12 theme APOBEC3 2349:2355 arg1 proteins 2357:2364 APOBEC3 proteins 2349:2364 APOBEC3 proteins 2349:2364 We show that gammaretroviruses expressing an accessory protein called glycosylated Gag, or gPr80, use the host's posttranslational machinery and, more specifically, N-linked glycosylation as a way to modulate their sensitivity to mutations by APOBEC3 proteins. 25505062 5 13 theme deamination-independent 813:835 arg1 restriction 837:847 deamination-independent restriction 813:847 deamination-independent restriction 813:847 Here we show that gPr80 exerts two distinct inhibitory effects on mA3: one that antagonizes deamination-independent restriction and another one that inhibits its deaminase activity. 25505062 12 14 theme recognized 1995:2004 arg1 way 2006:2008 a newly recognized way 1987:2008 a newly recognized way in which some retroviruses protect themselves against the mutator activity of APOBEC3 proteins 1987:2103 Here we describe a newly recognized way in which some retroviruses protect themselves against the mutator activity of APOBEC3 proteins. 25505062 10 15 contain have 1756:1759 arg1 factors 1743:1749 host factors 1738:1749 host factors that have a major role in protecting humans and other mammals against retroviruses 1738:1832 IMPORTANCE: APOBEC3 proteins are host factors that have a major role in protecting humans and other mammals against retroviruses. 25505062 10 15 contain have 1756:1759 arg2 role 1769:1772 a major role 1761:1772 a major role 1761:1772 IMPORTANCE: APOBEC3 proteins are host factors that have a major role in protecting humans and other mammals against retroviruses. 25505062 10 15 contain have 1756:1759 arg1 IMPORTANCE 1705:1714 IMPORTANCE 1705:1714 IMPORTANCE: APOBEC3 proteins 1705:1732 IMPORTANCE: APOBEC3 proteins are host factors that have a major role in protecting humans and other mammals against retroviruses. 25505062 4 16 theme mouse 705:709 arg1 mA3 715:717 mA3 715:717 mA3 715:717 Glycosylated Gag, also called glycosylated Pr80 Gag (gPr80), is a gammaretrovirus genome-encoded protein that inhibits the antiretroviral activity of mouse A3 (mA3). 25505062 4 16 theme mouse 705:709 arg1 A3 711:712 mouse A3 705:712 mouse A3 (mA3) 705:718 Glycosylated Gag, also called glycosylated Pr80 Gag (gPr80), is a gammaretrovirus genome-encoded protein that inhibits the antiretroviral activity of mouse A3 (mA3). 25505062 12 17 theme proteins 2096:2103 arg1 activity 2076:2083 the mutator activity 2064:2083 the mutator activity of APOBEC3 proteins 2064:2103 Here we describe a newly recognized way in which some retroviruses protect themselves against the mutator activity of APOBEC3 proteins. 25505062 7 18 theme germ 1207:1210 arg1 line 1212:1215 the mouse germ line 1197:1215 the mouse germ line 1197:1215 Finally, our work highlights that retroviruses which have successfully integrated into the mouse germ line generally express a gPr80 with fewer glycosylated sites than exogenous retroviruses. 25505062 2 19 theme intrinsic 242:250 arg1 proteins 294:301 APOBEC3 (A3) proteins 281:301 APOBEC3 (A3) proteins 281:301 Host intrinsic restriction factors, such as APOBEC3 (A3) proteins, are constitutively expressed and dedicated to interfering with the replication cycle of retroviruses. 25505062 2 19 theme intrinsic 242:250 arg1 factors 264:270 Host intrinsic restriction factors 237:270 Host intrinsic restriction factors 237:270 Host intrinsic restriction factors, such as APOBEC3 (A3) proteins, are constitutively expressed and dedicated to interfering with the replication cycle of retroviruses. 25505062 1 20 theme disease 170:176 arg1 source 160:165 a source 158:165 a source of disease, genome instability, and tumor development in their hosts 158:234 Retroviruses are pathogens with rapid infection cycles that can be a source of disease, genome instability, and tumor development in their hosts. 25505062 1 20 theme disease 170:176 arg1 cycles 139:144 rapid infection cycles 123:144 rapid infection cycles that can be a source of disease, genome instability, and tumor development in their hosts 123:234 Retroviruses are pathogens with rapid infection cycles that can be a source of disease, genome instability, and tumor development in their hosts. 25505062 13 21 dep way 2299:2301 arg1 modulate 2306:2313 modulate 2306:2313 to modulate their sensitivity to mutations by APOBEC3 proteins 2303:2364 We show that gammaretroviruses expressing an accessory protein called glycosylated Gag, or gPr80, use the host's posttranslational machinery and, more specifically, N-linked glycosylation as a way to modulate their sensitivity to mutations by APOBEC3 proteins. 25505062 3 22 theme accessory 535:543 arg1 proteins 545:552 virus genome-encoded accessory proteins 514:552 virus genome-encoded accessory proteins 514:552 To survive, propagate, and persist, retroviruses must counteract these restriction factors, often by way of virus genome-encoded accessory proteins. 25505062 6 23 theme residues 964:971 arg1 number 939:944 the number 935:944 the number of N-glycosylated residues in gPr80 935:980 More specifically, we find that the number of N-glycosylated residues in gPr80 inversely correlates with the sensitivity of a gammaretrovirus to deamination by mouse A3 and also, surprisingly, by human A3G. 25505062 7 24 dep glycosylated 1254:1265 arg1 fewer 1248:1252 fewer 1248:1252 fewer 1248:1252 Finally, our work highlights that retroviruses which have successfully integrated into the mouse germ line generally express a gPr80 with fewer glycosylated sites than exogenous retroviruses. 25505062 6 25 theme mouse 1063:1067 arg1 A3 1069:1070 mouse A3 1063:1070 mouse A3 1063:1070 More specifically, we find that the number of N-glycosylated residues in gPr80 inversely correlates with the sensitivity of a gammaretrovirus to deamination by mouse A3 and also, surprisingly, by human A3G. 25505062 8 26 theme A3 1362:1363 arg1 intensity 1377:1385 A3 deamination intensity 1362:1385 A3 deamination intensity 1362:1385 This observation supports the suggestion that modulation of A3 deamination intensity could be a desirable attribute for retroviruses to increase genetic diversification and avoid immune detection. 25505062 2 27 theme replication 371:381 arg1 cycle 383:387 the replication cycle 367:387 the replication cycle of retroviruses 367:403 Host intrinsic restriction factors, such as APOBEC3 (A3) proteins, are constitutively expressed and dedicated to interfering with the replication cycle of retroviruses. 25505062 0 28 theme N-linked 0:7 arg1 glycosylation 9:21 N-linked glycosylation 0:21 N-linked glycosylation 0:21 N-linked glycosylation protects gammaretroviruses against deamination by APOBEC3 proteins. 25505062 6 29 from number 939:944 arg1 gPr80 976:980 gPr80 976:980 gPr80 976:980 More specifically, we find that the number of N-glycosylated residues in gPr80 inversely correlates with the sensitivity of a gammaretrovirus to deamination by mouse A3 and also, surprisingly, by human A3G. 25505062 8 30 theme intensity 1377:1385 arg1 modulation 1348:1357 modulation 1348:1357 modulation of A3 deamination intensity 1348:1385 This observation supports the suggestion that modulation of A3 deamination intensity could be a desirable attribute for retroviruses to increase genetic diversification and avoid immune detection. 25505062 8 30 theme intensity 1377:1385 arg1 attribute 1408:1416 a desirable attribute 1396:1416 a desirable attribute for retroviruses to increase genetic diversification and avoid immune detection 1396:1496 This observation supports the suggestion that modulation of A3 deamination intensity could be a desirable attribute for retroviruses to increase genetic diversification and avoid immune detection. 25505062 1 31 theme infection 129:137 arg1 source 160:165 a source 158:165 a source of disease, genome instability, and tumor development in their hosts 158:234 Retroviruses are pathogens with rapid infection cycles that can be a source of disease, genome instability, and tumor development in their hosts. 25505062 1 31 theme infection 129:137 arg1 cycles 139:144 rapid infection cycles 123:144 rapid infection cycles that can be a source of disease, genome instability, and tumor development in their hosts 123:234 Retroviruses are pathogens with rapid infection cycles that can be a source of disease, genome instability, and tumor development in their hosts. 25505062 6 32 theme gammaretrovirus 1029:1043 arg1 sensitivity 1012:1022 the sensitivity 1008:1022 the sensitivity of a gammaretrovirus to deamination by mouse A3 and also, surprisingly, by human A3G 1008:1107 More specifically, we find that the number of N-glycosylated residues in gPr80 inversely correlates with the sensitivity of a gammaretrovirus to deamination by mouse A3 and also, surprisingly, by human A3G. 25505062 4 33 theme Glycosylated 555:566 arg1 protein 652:658 a gammaretrovirus genome-encoded protein 619:658 a gammaretrovirus genome-encoded protein that inhibits the antiretroviral activity of mouse A3 (mA3) 619:718 Glycosylated Gag, also called glycosylated Pr80 Gag (gPr80), is a gammaretrovirus genome-encoded protein that inhibits the antiretroviral activity of mouse A3 (mA3). 25505062 4 33 theme Glycosylated 555:566 arg1 Gag 568:570 Glycosylated Gag 555:570 Glycosylated Gag 555:570 Glycosylated Gag, also called glycosylated Pr80 Gag (gPr80), is a gammaretrovirus genome-encoded protein that inhibits the antiretroviral activity of mouse A3 (mA3). 25505062 11 34 theme infection 1959:1967 arg1 spread 1949:1954 the spread 1945:1954 the spread of infection 1945:1967 These enzymes hinder their replication and intensely mutate their DNA, thereby inactivating viral progeny and the spread of infection. 25505062 11 34 theme infection 1959:1967 arg1 progeny 1933:1939 viral progeny 1927:1939 viral progeny 1927:1939 These enzymes hinder their replication and intensely mutate their DNA, thereby inactivating viral progeny and the spread of infection. 25505062 8 35 theme desirable 1398:1406 arg1 modulation 1348:1357 modulation 1348:1357 modulation of A3 deamination intensity 1348:1385 This observation supports the suggestion that modulation of A3 deamination intensity could be a desirable attribute for retroviruses to increase genetic diversification and avoid immune detection. 25505062 8 35 theme desirable 1398:1406 arg1 attribute 1408:1416 a desirable attribute 1396:1416 a desirable attribute for retroviruses to increase genetic diversification and avoid immune detection 1396:1496 This observation supports the suggestion that modulation of A3 deamination intensity could be a desirable attribute for retroviruses to increase genetic diversification and avoid immune detection. 25505062 3 36 theme restriction 477:487 arg1 factors 489:495 these restriction factors 471:495 these restriction factors 471:495 To survive, propagate, and persist, retroviruses must counteract these restriction factors, often by way of virus genome-encoded accessory proteins. 25505062 5 37 theme inhibitory 765:774 arg1 effects 776:782 two distinct inhibitory effects 752:782 two distinct inhibitory effects 752:782 Here we show that gPr80 exerts two distinct inhibitory effects on mA3: one that antagonizes deamination-independent restriction and another one that inhibits its deaminase activity. 25505062 6 38 theme human 1099:1103 arg1 A3G 1105:1107 human A3G 1099:1107 human A3G 1099:1107 More specifically, we find that the number of N-glycosylated residues in gPr80 inversely correlates with the sensitivity of a gammaretrovirus to deamination by mouse A3 and also, surprisingly, by human A3G. 25505062 10 39 theme host 1738:1741 arg1 factors 1743:1749 host factors 1738:1749 host factors that have a major role in protecting humans and other mammals against retroviruses 1738:1832 IMPORTANCE: APOBEC3 proteins are host factors that have a major role in protecting humans and other mammals against retroviruses. 25505062 10 39 theme host 1738:1741 arg1 IMPORTANCE 1705:1714 IMPORTANCE 1705:1714 IMPORTANCE: APOBEC3 proteins 1705:1732 IMPORTANCE: APOBEC3 proteins are host factors that have a major role in protecting humans and other mammals against retroviruses. 25505062 4 40 theme Pr80 598:601 arg1 Gag 603:605 glycosylated Pr80 Gag 585:605 glycosylated Pr80 Gag (gPr80) 585:613 Glycosylated Gag, also called glycosylated Pr80 Gag (gPr80), is a gammaretrovirus genome-encoded protein that inhibits the antiretroviral activity of mouse A3 (mA3). 25505062 4 40 theme Pr80 598:601 arg1 gPr80 608:612 gPr80 608:612 gPr80 608:612 Glycosylated Gag, also called glycosylated Pr80 Gag (gPr80), is a gammaretrovirus genome-encoded protein that inhibits the antiretroviral activity of mouse A3 (mA3). 25505062 11 41 theme viral 1927:1931 arg1 progeny 1933:1939 viral progeny 1927:1939 viral progeny 1927:1939 These enzymes hinder their replication and intensely mutate their DNA, thereby inactivating viral progeny and the spread of infection. 25505062 4 42 theme gammaretrovirus 621:635 arg1 protein 652:658 a gammaretrovirus genome-encoded protein 619:658 a gammaretrovirus genome-encoded protein that inhibits the antiretroviral activity of mouse A3 (mA3) 619:718 Glycosylated Gag, also called glycosylated Pr80 Gag (gPr80), is a gammaretrovirus genome-encoded protein that inhibits the antiretroviral activity of mouse A3 (mA3). 25505062 4 42 theme gammaretrovirus 621:635 arg1 Gag 568:570 Glycosylated Gag 555:570 Glycosylated Gag 555:570 Glycosylated Gag, also called glycosylated Pr80 Gag (gPr80), is a gammaretrovirus genome-encoded protein that inhibits the antiretroviral activity of mouse A3 (mA3). 25505062 13 43 theme posttranslational 2219:2235 arg1 glycosylation 2280:2292 N-linked glycosylation 2271:2292 N-linked glycosylation 2271:2292 We show that gammaretroviruses expressing an accessory protein called glycosylated Gag, or gPr80, use the host's posttranslational machinery and, more specifically, N-linked glycosylation as a way to modulate their sensitivity to mutations by APOBEC3 proteins. 25505062 13 43 theme posttranslational 2219:2235 arg1 way 2299:2301 a way 2297:2301 a way to modulate their sensitivity to mutations by APOBEC3 proteins 2297:2364 We show that gammaretroviruses expressing an accessory protein called glycosylated Gag, or gPr80, use the host's posttranslational machinery and, more specifically, N-linked glycosylation as a way to modulate their sensitivity to mutations by APOBEC3 proteins. 25505062 13 43 theme posttranslational 2219:2235 arg1 machinery 2237:2245 the host's posttranslational machinery 2208:2245 the host's posttranslational machinery 2208:2245 We show that gammaretroviruses expressing an accessory protein called glycosylated Gag, or gPr80, use the host's posttranslational machinery and, more specifically, N-linked glycosylation as a way to modulate their sensitivity to mutations by APOBEC3 proteins. 25505062 5 44 theme distinct 756:763 arg1 effects 776:782 two distinct inhibitory effects 752:782 two distinct inhibitory effects 752:782 Here we show that gPr80 exerts two distinct inhibitory effects on mA3: one that antagonizes deamination-independent restriction and another one that inhibits its deaminase activity. 25505062 9 45 theme genome-encoded 1659:1672 arg1 factor 1697:1702 a host genome-encoded retroviral restriction factor 1652:1702 a host genome-encoded retroviral restriction factor 1652:1702 Overall, we present here the first description of how gammaretroviruses employ posttranslational modification to antagonize and modulate the activity of a host genome-encoded retroviral restriction factor. 25505062 13 46 link N-linked 2271:2278 arg1 glycosylation 2280:2292 N-linked glycosylation 2271:2292 N-linked glycosylation 2271:2292 We show that gammaretroviruses expressing an accessory protein called glycosylated Gag, or gPr80, use the host's posttranslational machinery and, more specifically, N-linked glycosylation as a way to modulate their sensitivity to mutations by APOBEC3 proteins. 25505062 13 46 link N-linked 2271:2278 arg1 way 2299:2301 a way 2297:2301 a way to modulate their sensitivity to mutations by APOBEC3 proteins 2297:2364 We show that gammaretroviruses expressing an accessory protein called glycosylated Gag, or gPr80, use the host's posttranslational machinery and, more specifically, N-linked glycosylation as a way to modulate their sensitivity to mutations by APOBEC3 proteins. 25505062 13 46 link N-linked 2271:2278 arg1 machinery 2237:2245 the host's posttranslational machinery 2208:2245 the host's posttranslational machinery 2208:2245 We show that gammaretroviruses expressing an accessory protein called glycosylated Gag, or gPr80, use the host's posttranslational machinery and, more specifically, N-linked glycosylation as a way to modulate their sensitivity to mutations by APOBEC3 proteins. 25505062 9 47 theme restriction 1685:1695 arg1 factor 1697:1702 a host genome-encoded retroviral restriction factor 1652:1702 a host genome-encoded retroviral restriction factor 1652:1702 Overall, we present here the first description of how gammaretroviruses employ posttranslational modification to antagonize and modulate the activity of a host genome-encoded retroviral restriction factor. 25505062 1 48 theme tumor 203:207 arg1 development 209:219 tumor development 203:219 tumor development 203:219 Retroviruses are pathogens with rapid infection cycles that can be a source of disease, genome instability, and tumor development in their hosts. 25505062 14 49 theme mutations 2406:2414 arg1 mutations 2406:2414 mutations 2406:2414 mutations caused by APOBEC3 proteins 2406:2441 By carefully controlling the amount of mutations caused by APOBEC3 proteins, gammaretroviruses can find a balance that helps them evolve and persist. 25505062 14 49 theme mutations 2406:2414 arg1 amount 2396:2401 the amount 2392:2401 the amount of mutations caused by APOBEC3 proteins 2392:2441 By carefully controlling the amount of mutations caused by APOBEC3 proteins, gammaretroviruses can find a balance that helps them evolve and persist. 25505062 3 50 theme genome-encoded 520:533 arg1 proteins 545:552 virus genome-encoded accessory proteins 514:552 virus genome-encoded accessory proteins 514:552 To survive, propagate, and persist, retroviruses must counteract these restriction factors, often by way of virus genome-encoded accessory proteins. 25505062 7 51 with gPr80 1237:1241 arg1 sites 1267:1271 fewer glycosylated sites 1248:1271 fewer glycosylated sites than exogenous retroviruses 1248:1299 Finally, our work highlights that retroviruses which have successfully integrated into the mouse germ line generally express a gPr80 with fewer glycosylated sites than exogenous retroviruses. 25505062 13 52 gly glycosylated 2176:2187 arg1 Gag 2189:2191 glycosylated Gag 2176:2191 glycosylated Gag 2176:2191 We show that gammaretroviruses expressing an accessory protein called glycosylated Gag, or gPr80, use the host's posttranslational machinery and, more specifically, N-linked glycosylation as a way to modulate their sensitivity to mutations by APOBEC3 proteins. 25505062 6 53 gly N-glycosylated 949:962 arg1 residues 964:971 N-glycosylated residues 949:971 N-glycosylated residues in gPr80 949:980 More specifically, we find that the number of N-glycosylated residues in gPr80 inversely correlates with the sensitivity of a gammaretrovirus to deamination by mouse A3 and also, surprisingly, by human A3G. 25505062 1 54 theme instability 186:196 arg1 source 160:165 a source 158:165 a source of disease, genome instability, and tumor development in their hosts 158:234 Retroviruses are pathogens with rapid infection cycles that can be a source of disease, genome instability, and tumor development in their hosts. 25505062 1 54 theme instability 186:196 arg1 cycles 139:144 rapid infection cycles 123:144 rapid infection cycles that can be a source of disease, genome instability, and tumor development in their hosts 123:234 Retroviruses are pathogens with rapid infection cycles that can be a source of disease, genome instability, and tumor development in their hosts. 25505062 6 55 theme N-glycosylated 949:962 arg1 residues 964:971 N-glycosylated residues 949:971 N-glycosylated residues in gPr80 949:980 More specifically, we find that the number of N-glycosylated residues in gPr80 inversely correlates with the sensitivity of a gammaretrovirus to deamination by mouse A3 and also, surprisingly, by human A3G. 25505062 3 56 theme proteins 545:552 arg1 way 507:509 way 507:509 way of virus genome-encoded accessory proteins 507:552 To survive, propagate, and persist, retroviruses must counteract these restriction factors, often by way of virus genome-encoded accessory proteins. 25505062 8 57 theme genetic 1447:1453 arg1 diversification 1455:1469 genetic diversification 1447:1469 genetic diversification 1447:1469 This observation supports the suggestion that modulation of A3 deamination intensity could be a desirable attribute for retroviruses to increase genetic diversification and avoid immune detection. 25505062 5 58 theme deaminase 883:891 arg1 activity 893:900 its deaminase activity 879:900 its deaminase activity 879:900 Here we show that gPr80 exerts two distinct inhibitory effects on mA3: one that antagonizes deamination-independent restriction and another one that inhibits its deaminase activity. 25505062 7 59 theme glycosylated 1254:1265 arg1 sites 1267:1271 fewer glycosylated sites 1248:1271 fewer glycosylated sites than exogenous retroviruses 1248:1299 Finally, our work highlights that retroviruses which have successfully integrated into the mouse germ line generally express a gPr80 with fewer glycosylated sites than exogenous retroviruses. 25505062 2 60 theme Host 237:240 arg1 proteins 294:301 APOBEC3 (A3) proteins 281:301 APOBEC3 (A3) proteins 281:301 Host intrinsic restriction factors, such as APOBEC3 (A3) proteins, are constitutively expressed and dedicated to interfering with the replication cycle of retroviruses. 25505062 2 60 theme Host 237:240 arg1 factors 264:270 Host intrinsic restriction factors 237:270 Host intrinsic restriction factors 237:270 Host intrinsic restriction factors, such as APOBEC3 (A3) proteins, are constitutively expressed and dedicated to interfering with the replication cycle of retroviruses. 25505062 1 61 theme development 209:219 arg1 source 160:165 a source 158:165 a source of disease, genome instability, and tumor development in their hosts 158:234 Retroviruses are pathogens with rapid infection cycles that can be a source of disease, genome instability, and tumor development in their hosts. 25505062 1 61 theme development 209:219 arg1 cycles 139:144 rapid infection cycles 123:144 rapid infection cycles that can be a source of disease, genome instability, and tumor development in their hosts 123:234 Retroviruses are pathogens with rapid infection cycles that can be a source of disease, genome instability, and tumor development in their hosts. 25505062 5 62 dep show 729:732 arg1 one 792:794 one 792:794 one 792:794 Here we show that gPr80 exerts two distinct inhibitory effects on mA3: one that antagonizes deamination-independent restriction and another one that inhibits its deaminase activity. 25505062 5 62 dep show 729:732 arg1 one 861:863 one 861:863 one 861:863 Here we show that gPr80 exerts two distinct inhibitory effects on mA3: one that antagonizes deamination-independent restriction and another one that inhibits its deaminase activity. 25505062 8 63 theme immune 1481:1486 arg1 detection 1488:1496 immune detection 1481:1496 immune detection 1481:1496 This observation supports the suggestion that modulation of A3 deamination intensity could be a desirable attribute for retroviruses to increase genetic diversification and avoid immune detection. 25505062 13 64 theme accessory 2151:2159 arg1 protein 2161:2167 an accessory protein 2148:2167 an accessory protein called glycosylated Gag 2148:2191 We show that gammaretroviruses expressing an accessory protein called glycosylated Gag, or gPr80, use the host's posttranslational machinery and, more specifically, N-linked glycosylation as a way to modulate their sensitivity to mutations by APOBEC3 proteins. 25505062 4 65 theme A3 711:712 arg1 activity 693:700 the antiretroviral activity 674:700 the antiretroviral activity of mouse A3 (mA3) 674:718 Glycosylated Gag, also called glycosylated Pr80 Gag (gPr80), is a gammaretrovirus genome-encoded protein that inhibits the antiretroviral activity of mouse A3 (mA3). 25505062 7 66 theme mouse 1201:1205 arg1 line 1212:1215 the mouse germ line 1197:1215 the mouse germ line 1197:1215 Finally, our work highlights that retroviruses which have successfully integrated into the mouse germ line generally express a gPr80 with fewer glycosylated sites than exogenous retroviruses. 25505062 2 67 theme restriction 252:262 arg1 proteins 294:301 APOBEC3 (A3) proteins 281:301 APOBEC3 (A3) proteins 281:301 Host intrinsic restriction factors, such as APOBEC3 (A3) proteins, are constitutively expressed and dedicated to interfering with the replication cycle of retroviruses. 25505062 2 67 theme restriction 252:262 arg1 factors 264:270 Host intrinsic restriction factors 237:270 Host intrinsic restriction factors 237:270 Host intrinsic restriction factors, such as APOBEC3 (A3) proteins, are constitutively expressed and dedicated to interfering with the replication cycle of retroviruses. 25505062 12 68 theme APOBEC3 2088:2094 arg1 proteins 2096:2103 APOBEC3 proteins 2088:2103 APOBEC3 proteins 2088:2103 Here we describe a newly recognized way in which some retroviruses protect themselves against the mutator activity of APOBEC3 proteins. 25505062 9 69 theme first 1528:1532 arg1 description 1534:1544 the first description 1524:1544 the first description of how gammaretroviruses employ posttranslational modification to antagonize and modulate the activity of a host genome-encoded retroviral restriction factor 1524:1702 Overall, we present here the first description of how gammaretroviruses employ posttranslational modification to antagonize and modulate the activity of a host genome-encoded retroviral restriction factor. 25505062 4 70 theme antiretroviral 678:691 arg1 activity 693:700 the antiretroviral activity 674:700 the antiretroviral activity of mouse A3 (mA3) 674:718 Glycosylated Gag, also called glycosylated Pr80 Gag (gPr80), is a gammaretrovirus genome-encoded protein that inhibits the antiretroviral activity of mouse A3 (mA3). 25505062 10 71 theme other 1799:1803 arg1 mammals 1805:1811 other mammals 1799:1811 other mammals 1799:1811 IMPORTANCE: APOBEC3 proteins are host factors that have a major role in protecting humans and other mammals against retroviruses. 25505062 1 72 from source 160:165 arg1 hosts 230:234 their hosts 224:234 their hosts 224:234 Retroviruses are pathogens with rapid infection cycles that can be a source of disease, genome instability, and tumor development in their hosts. 25505062 6 73 from residues 964:971 arg1 gPr80 976:980 gPr80 976:980 gPr80 976:980 More specifically, we find that the number of N-glycosylated residues in gPr80 inversely correlates with the sensitivity of a gammaretrovirus to deamination by mouse A3 and also, surprisingly, by human A3G. 25505062 9 74 theme posttranslational 1578:1594 arg1 modification 1596:1607 posttranslational modification 1578:1607 posttranslational modification 1578:1607 Overall, we present here the first description of how gammaretroviruses employ posttranslational modification to antagonize and modulate the activity of a host genome-encoded retroviral restriction factor. 25505062 6 75 from gPr80 976:980 arg1 number 939:944 the number 935:944 the number of N-glycosylated residues in gPr80 935:980 More specifically, we find that the number of N-glycosylated residues in gPr80 inversely correlates with the sensitivity of a gammaretrovirus to deamination by mouse A3 and also, surprisingly, by human A3G. 25505062 13 76 theme N-linked 2271:2278 arg1 glycosylation 2280:2292 N-linked glycosylation 2271:2292 N-linked glycosylation 2271:2292 We show that gammaretroviruses expressing an accessory protein called glycosylated Gag, or gPr80, use the host's posttranslational machinery and, more specifically, N-linked glycosylation as a way to modulate their sensitivity to mutations by APOBEC3 proteins. 25505062 13 76 theme N-linked 2271:2278 arg1 way 2299:2301 a way 2297:2301 a way to modulate their sensitivity to mutations by APOBEC3 proteins 2297:2364 We show that gammaretroviruses expressing an accessory protein called glycosylated Gag, or gPr80, use the host's posttranslational machinery and, more specifically, N-linked glycosylation as a way to modulate their sensitivity to mutations by APOBEC3 proteins. 25505062 13 76 theme N-linked 2271:2278 arg1 machinery 2237:2245 the host's posttranslational machinery 2208:2245 the host's posttranslational machinery 2208:2245 We show that gammaretroviruses expressing an accessory protein called glycosylated Gag, or gPr80, use the host's posttranslational machinery and, more specifically, N-linked glycosylation as a way to modulate their sensitivity to mutations by APOBEC3 proteins. 25505062 4 77 gly glycosylated 585:596 arg1 Gag 603:605 glycosylated Pr80 Gag 585:605 glycosylated Pr80 Gag (gPr80) 585:613 Glycosylated Gag, also called glycosylated Pr80 Gag (gPr80), is a gammaretrovirus genome-encoded protein that inhibits the antiretroviral activity of mouse A3 (mA3). 25505062 4 77 gly glycosylated 585:596 arg1 gPr80 608:612 gPr80 608:612 gPr80 608:612 Glycosylated Gag, also called glycosylated Pr80 Gag (gPr80), is a gammaretrovirus genome-encoded protein that inhibits the antiretroviral activity of mouse A3 (mA3). 25505062 1 78 theme rapid 123:127 arg1 source 160:165 a source 158:165 a source of disease, genome instability, and tumor development in their hosts 158:234 Retroviruses are pathogens with rapid infection cycles that can be a source of disease, genome instability, and tumor development in their hosts. 25505062 1 78 theme rapid 123:127 arg1 cycles 139:144 rapid infection cycles 123:144 rapid infection cycles that can be a source of disease, genome instability, and tumor development in their hosts 123:234 Retroviruses are pathogens with rapid infection cycles that can be a source of disease, genome instability, and tumor development in their hosts. 25505062 7 79 theme exogenous 1278:1286 arg1 retroviruses 1288:1299 exogenous retroviruses 1278:1299 exogenous retroviruses 1278:1299 Finally, our work highlights that retroviruses which have successfully integrated into the mouse germ line generally express a gPr80 with fewer glycosylated sites than exogenous retroviruses. 25505062 8 80 theme deamination 1365:1375 arg1 intensity 1377:1385 A3 deamination intensity 1362:1385 A3 deamination intensity 1362:1385 This observation supports the suggestion that modulation of A3 deamination intensity could be a desirable attribute for retroviruses to increase genetic diversification and avoid immune detection. 25505062 10 81 theme APOBEC3 1717:1723 arg1 proteins 1725:1732 APOBEC3 proteins 1717:1732 IMPORTANCE: APOBEC3 proteins 1705:1732 IMPORTANCE: APOBEC3 proteins are host factors that have a major role in protecting humans and other mammals against retroviruses. 25505062 10 82 dep IMPORTANCE 1705:1714 arg1 proteins 1725:1732 APOBEC3 proteins 1717:1732 IMPORTANCE: APOBEC3 proteins 1705:1732 IMPORTANCE: APOBEC3 proteins are host factors that have a major role in protecting humans and other mammals against retroviruses. 25505062 2 83 theme retroviruses 392:403 arg1 cycle 383:387 the replication cycle 367:387 the replication cycle of retroviruses 367:403 Host intrinsic restriction factors, such as APOBEC3 (A3) proteins, are constitutively expressed and dedicated to interfering with the replication cycle of retroviruses. 25505062 0 84 theme APOBEC3 73:79 arg1 proteins 81:88 APOBEC3 proteins 73:88 APOBEC3 proteins 73:88 N-linked glycosylation protects gammaretroviruses against deamination by APOBEC3 proteins. 25505062 7 85 gly glycosylated 1254:1265 arg1 sites 1267:1271 fewer glycosylated sites 1248:1271 fewer glycosylated sites than exogenous retroviruses 1248:1299 Finally, our work highlights that retroviruses which have successfully integrated into the mouse germ line generally express a gPr80 with fewer glycosylated sites than exogenous retroviruses. 25505062 12 86 theme mutator 2068:2074 arg1 activity 2076:2083 the mutator activity 2064:2083 the mutator activity of APOBEC3 proteins 2064:2103 Here we describe a newly recognized way in which some retroviruses protect themselves against the mutator activity of APOBEC3 proteins. 25505062 9 87 theme host 1654:1657 arg1 factor 1697:1702 a host genome-encoded retroviral restriction factor 1652:1702 a host genome-encoded retroviral restriction factor 1652:1702 Overall, we present here the first description of how gammaretroviruses employ posttranslational modification to antagonize and modulate the activity of a host genome-encoded retroviral restriction factor. 25505062 10 88 theme major 1763:1767 arg1 role 1769:1772 a major role 1761:1772 a major role 1761:1772 IMPORTANCE: APOBEC3 proteins are host factors that have a major role in protecting humans and other mammals against retroviruses. 26100877 6 0 from activation 946:955 arg1 efficacy 912:919 a greater efficacy 902:919 a greater efficacy at G12/13-dependent RhoA activation 902:955 In contrast, wildtype PAR1 displayed a greater efficacy at G12/13-dependent RhoA activation compared with mutant receptor lacking glycosylation at ECL2. 26100877 11 1 theme state 1779:1783 arg1 stabilization 1747:1759 the stabilization 1743:1759 the stabilization of an active PAR1 state that preferentially couples to G12/13 versus Gq and defines a previously unidentified function for N-linked glycosylation of GPCRs in regulating G-protein signaling bias 1743:1953 These studies suggest that N-linked glycosylation at ECL2 contributes to the stabilization of an active PAR1 state that preferentially couples to G12/13 versus Gq and defines a previously unidentified function for N-linked glycosylation of GPCRs in regulating G-protein signaling bias. 26100877 7 2 theme opposite 1194:1201 arg1 activation 1183:1192 RhoA activation 1178:1192 RhoA activation opposite to native receptor 1178:1220 Endogenous PAR1 rendered deficient in glycosylation using tunicamycin, a glycoprotein synthesis inhibitor, also exhibited increased PI signaling and diminished RhoA activation opposite to native receptor. 26100877 5 3 from deficient 711:719 arg1 glycosylation 724:736 glycosylation 724:736 glycosylation at ECL2 724:744 A PAR1 mutant deficient in glycosylation at ECL2 was more effective at stimulating Gq-mediated phosphoinositide signaling compared with glycosylated wildtype receptor. 26100877 6 4 theme G12/13-dependent 924:939 arg1 activation 946:955 G12/13-dependent RhoA activation 924:955 G12/13-dependent RhoA activation 924:955 In contrast, wildtype PAR1 displayed a greater efficacy at G12/13-dependent RhoA activation compared with mutant receptor lacking glycosylation at ECL2. 26100877 7 5 theme RhoA 1178:1181 arg1 activation 1183:1192 RhoA activation 1178:1192 RhoA activation opposite to native receptor 1178:1220 Endogenous PAR1 rendered deficient in glycosylation using tunicamycin, a glycoprotein synthesis inhibitor, also exhibited increased PI signaling and diminished RhoA activation opposite to native receptor. 26100877 8 6 theme wildtype 1240:1247 arg1 mutant 1277:1282 PAR1 wildtype and glycosylation-deficient mutant 1235:1282 PAR1 wildtype and glycosylation-deficient mutant 1235:1282 Remarkably, PAR1 wildtype and glycosylation-deficient mutant were equally effective at coupling to Gi and β-arrestin-1. 26100877 0 7 link N-linked 0:7 arg1 glycosylation 9:21 N-linked glycosylation 0:21 N-linked glycosylation of protease-activated receptor-1 at extracellular loop 2 0:78 N-linked glycosylation of protease-activated receptor-1 at extracellular loop 2 regulates G-protein signaling bias. 26100877 3 8 with activation 422:431 arg1 ligand 463:468 the same ligand 454:468 the same ligand 454:468 The molecular mechanism by which activation of a given GPCR with the same ligand permits coupling to multiple G-protein subtypes is unclear. 26100877 8 9 theme glycosylation-deficient 1253:1275 arg1 mutant 1277:1282 PAR1 wildtype and glycosylation-deficient mutant 1235:1282 PAR1 wildtype and glycosylation-deficient mutant 1235:1282 Remarkably, PAR1 wildtype and glycosylation-deficient mutant were equally effective at coupling to Gi and β-arrestin-1. 26100877 6 10 theme RhoA 941:944 arg1 activation 946:955 G12/13-dependent RhoA activation 924:955 G12/13-dependent RhoA activation 924:955 In contrast, wildtype PAR1 displayed a greater efficacy at G12/13-dependent RhoA activation compared with mutant receptor lacking glycosylation at ECL2. 26100877 7 11 theme PI 1150:1151 arg1 signaling 1153:1161 increased PI signaling 1140:1161 increased PI signaling 1140:1161 Endogenous PAR1 rendered deficient in glycosylation using tunicamycin, a glycoprotein synthesis inhibitor, also exhibited increased PI signaling and diminished RhoA activation opposite to native receptor. 26100877 6 12 gly glycosylation 995:1007 arg1 ECL2 1012:1015 ECL2 1012:1015 ECL2 1012:1015 In contrast, wildtype PAR1 displayed a greater efficacy at G12/13-dependent RhoA activation compared with mutant receptor lacking glycosylation at ECL2. 26100877 4 13 theme G12/13 622:627 arg1 specificity 648:658 G12/13 versus Gq coupling specificity 622:658 specificity 648:658 Here, we report that N-linked glycosylation of PAR1 at extracellular loop 2 (ECL2) controls G12/13 versus Gq coupling specificity in response to thrombin stimulation. 26100877 5 14 theme PAR1 699:702 arg1 effective 755:763 effective 755:763 effective 755:763 A PAR1 mutant deficient in glycosylation at ECL2 was more effective at stimulating Gq-mediated phosphoinositide signaling compared with glycosylated wildtype receptor. 26100877 5 14 theme PAR1 699:702 arg1 mutant 704:709 A PAR1 mutant 697:709 A PAR1 mutant deficient in glycosylation at ECL2 697:744 A PAR1 mutant deficient in glycosylation at ECL2 was more effective at stimulating Gq-mediated phosphoinositide signaling compared with glycosylated wildtype receptor. 26100877 2 15 theme heterotrimeric 297:310 arg1 subtypes 322:329 multiple heterotrimeric G-protein subtypes 288:329 multiple heterotrimeric G-protein subtypes in the same cell 288:346 Similar to other GPCRs, PAR1 is promiscuous and couples to multiple heterotrimeric G-protein subtypes in the same cell and promotes diverse cellular responses. 26100877 1 16 theme protease 210:217 arg1 thrombin 219:226 the coagulant protease thrombin 196:226 the coagulant protease thrombin 196:226 Protease-activated receptor-1 (PAR1) is a G-protein-coupled receptor (GPCR) for the coagulant protease thrombin. 26100877 4 17 theme Gq 636:637 arg1 specificity 648:658 G12/13 versus Gq coupling specificity 622:658 specificity 648:658 Here, we report that N-linked glycosylation of PAR1 at extracellular loop 2 (ECL2) controls G12/13 versus Gq coupling specificity in response to thrombin stimulation. 26100877 5 18 theme deficient 711:719 arg1 effective 755:763 effective 755:763 effective 755:763 A PAR1 mutant deficient in glycosylation at ECL2 was more effective at stimulating Gq-mediated phosphoinositide signaling compared with glycosylated wildtype receptor. 26100877 5 18 theme deficient 711:719 arg1 mutant 704:709 A PAR1 mutant 697:709 A PAR1 mutant deficient in glycosylation at ECL2 697:744 A PAR1 mutant deficient in glycosylation at ECL2 was more effective at stimulating Gq-mediated phosphoinositide signaling compared with glycosylated wildtype receptor. 26100877 2 19 theme other 240:244 arg1 GPCRs 246:250 other GPCRs 240:250 other GPCRs 240:250 Similar to other GPCRs, PAR1 is promiscuous and couples to multiple heterotrimeric G-protein subtypes in the same cell and promotes diverse cellular responses. 26100877 7 20 theme using 1070:1074 arg1 tunicamycin 1076:1086 glycosylation using tunicamycin 1056:1086 glycosylation using tunicamycin 1056:1086 Endogenous PAR1 rendered deficient in glycosylation using tunicamycin, a glycoprotein synthesis inhibitor, also exhibited increased PI signaling and diminished RhoA activation opposite to native receptor. 26100877 5 21 theme glycosylated 833:844 arg1 receptor 855:862 glycosylated wildtype receptor 833:862 glycosylated wildtype receptor 833:862 A PAR1 mutant deficient in glycosylation at ECL2 was more effective at stimulating Gq-mediated phosphoinositide signaling compared with glycosylated wildtype receptor. 26100877 7 22 theme synthesis 1104:1112 arg1 PAR1 1029:1032 Endogenous PAR1 1018:1032 Endogenous PAR1 rendered deficient in glycosylation using tunicamycin 1018:1086 Endogenous PAR1 rendered deficient in glycosylation using tunicamycin, a glycoprotein synthesis inhibitor, also exhibited increased PI signaling and diminished RhoA activation opposite to native receptor. 26100877 7 22 theme synthesis 1104:1112 arg1 inhibitor 1114:1122 a glycoprotein synthesis inhibitor 1089:1122 a glycoprotein synthesis inhibitor 1089:1122 Endogenous PAR1 rendered deficient in glycosylation using tunicamycin, a glycoprotein synthesis inhibitor, also exhibited increased PI signaling and diminished RhoA activation opposite to native receptor. 26100877 4 23 gly glycosylation 560:572 arg1 ECL2 607:610 ECL2 607:610 ECL2 607:610 Here, we report that N-linked glycosylation of PAR1 at extracellular loop 2 (ECL2) controls G12/13 versus Gq coupling specificity in response to thrombin stimulation. 26100877 4 23 gly glycosylation 560:572 arg1 PAR1 577:580 PAR1 577:580 PAR1 577:580 Here, we report that N-linked glycosylation of PAR1 at extracellular loop 2 (ECL2) controls G12/13 versus Gq coupling specificity in response to thrombin stimulation. 26100877 4 23 gly glycosylation 560:572 arg1 loop 599:602 extracellular loop 2 585:604 extracellular loop 2 (ECL2) 585:611 Here, we report that N-linked glycosylation of PAR1 at extracellular loop 2 (ECL2) controls G12/13 versus Gq coupling specificity in response to thrombin stimulation. 26100877 4 23 gly glycosylation 560:572 arg2 loop 599:602 extracellular loop 2 585:604 extracellular loop 2 (ECL2) 585:611 Here, we report that N-linked glycosylation of PAR1 at extracellular loop 2 (ECL2) controls G12/13 versus Gq coupling specificity in response to thrombin stimulation. 26100877 4 23 gly glycosylation 560:572 arg2 ECL2 607:610 ECL2 607:610 ECL2 607:610 Here, we report that N-linked glycosylation of PAR1 at extracellular loop 2 (ECL2) controls G12/13 versus Gq coupling specificity in response to thrombin stimulation. 26100877 11 24 theme GPCRs 1910:1914 arg1 glycosylation 1893:1905 N-linked glycosylation 1884:1905 N-linked glycosylation of GPCRs 1884:1914 These studies suggest that N-linked glycosylation at ECL2 contributes to the stabilization of an active PAR1 state that preferentially couples to G12/13 versus Gq and defines a previously unidentified function for N-linked glycosylation of GPCRs in regulating G-protein signaling bias. 26100877 11 25 from ECL2 1723:1726 arg1 glycosylation 1706:1718 N-linked glycosylation 1697:1718 N-linked glycosylation at ECL2 1697:1726 These studies suggest that N-linked glycosylation at ECL2 contributes to the stabilization of an active PAR1 state that preferentially couples to G12/13 versus Gq and defines a previously unidentified function for N-linked glycosylation of GPCRs in regulating G-protein signaling bias. 26100877 4 26 theme thrombin 675:682 arg1 stimulation 684:694 thrombin stimulation 675:694 thrombin stimulation 675:694 Here, we report that N-linked glycosylation of PAR1 at extracellular loop 2 (ECL2) controls G12/13 versus Gq coupling specificity in response to thrombin stimulation. 26100877 9 27 theme G12/13 1372:1377 arg1 coupling 1379:1386 preferential G12/13 coupling 1359:1386 preferential G12/13 coupling 1359:1386 Consistent with preferential G12/13 coupling, thrombin-stimulated PAR1 wildtype strongly induced RhoA-mediated stress fiber formation compared with mutant receptor. 26100877 7 28 theme Endogenous 1018:1027 arg1 PAR1 1029:1032 Endogenous PAR1 1018:1032 Endogenous PAR1 rendered deficient in glycosylation using tunicamycin 1018:1086 Endogenous PAR1 rendered deficient in glycosylation using tunicamycin, a glycoprotein synthesis inhibitor, also exhibited increased PI signaling and diminished RhoA activation opposite to native receptor. 26100877 7 28 theme Endogenous 1018:1027 arg1 inhibitor 1114:1122 a glycoprotein synthesis inhibitor 1089:1122 a glycoprotein synthesis inhibitor 1089:1122 Endogenous PAR1 rendered deficient in glycosylation using tunicamycin, a glycoprotein synthesis inhibitor, also exhibited increased PI signaling and diminished RhoA activation opposite to native receptor. 26100877 1 29 theme G-protein-coupled 158:174 arg1 GPCR 186:189 GPCR 186:189 GPCR 186:189 Protease-activated receptor-1 (PAR1) is a G-protein-coupled receptor (GPCR) for the coagulant protease thrombin. 26100877 1 29 theme G-protein-coupled 158:174 arg1 receptor 176:183 a G-protein-coupled receptor 156:183 a G-protein-coupled receptor (GPCR) for the coagulant protease thrombin 156:226 Protease-activated receptor-1 (PAR1) is a G-protein-coupled receptor (GPCR) for the coagulant protease thrombin. 26100877 1 29 theme G-protein-coupled 158:174 arg1 receptor-1 135:144 Protease-activated receptor-1 116:144 Protease-activated receptor-1 (PAR1) 116:151 Protease-activated receptor-1 (PAR1) is a G-protein-coupled receptor (GPCR) for the coagulant protease thrombin. 26100877 11 30 theme signaling 1940:1948 arg1 bias 1950:1953 G-protein signaling bias 1930:1953 G-protein signaling bias 1930:1953 These studies suggest that N-linked glycosylation at ECL2 contributes to the stabilization of an active PAR1 state that preferentially couples to G12/13 versus Gq and defines a previously unidentified function for N-linked glycosylation of GPCRs in regulating G-protein signaling bias. 26100877 0 31 theme G-protein 90:98 arg1 bias 110:113 G-protein signaling bias 90:113 G-protein signaling bias 90:113 N-linked glycosylation of protease-activated receptor-1 at extracellular loop 2 regulates G-protein signaling bias. 26100877 3 32 theme GPCR 444:447 arg1 activation 422:431 activation 422:431 activation of a given GPCR with the same ligand 422:468 The molecular mechanism by which activation of a given GPCR with the same ligand permits coupling to multiple G-protein subtypes is unclear. 26100877 3 33 theme molecular 393:401 arg1 mechanism 403:411 The molecular mechanism 389:411 The molecular mechanism by which activation of a given GPCR with the same ligand permits coupling to multiple G-protein subtypes 389:516 The molecular mechanism by which activation of a given GPCR with the same ligand permits coupling to multiple G-protein subtypes is unclear. 26100877 3 33 theme molecular 393:401 arg1 unclear 521:527 unclear 521:527 unclear 521:527 The molecular mechanism by which activation of a given GPCR with the same ligand permits coupling to multiple G-protein subtypes is unclear. 26100877 5 34 gly glycosylation 724:736 arg1 ECL2 741:744 ECL2 741:744 ECL2 741:744 A PAR1 mutant deficient in glycosylation at ECL2 was more effective at stimulating Gq-mediated phosphoinositide signaling compared with glycosylated wildtype receptor. 26100877 5 34 gly glycosylation 724:736 arg2 ECL2 741:744 ECL2 741:744 ECL2 741:744 A PAR1 mutant deficient in glycosylation at ECL2 was more effective at stimulating Gq-mediated phosphoinositide signaling compared with glycosylated wildtype receptor. 26100877 9 35 with Consistent 1343:1352 arg1 coupling 1379:1386 preferential G12/13 coupling 1359:1386 preferential G12/13 coupling 1359:1386 Consistent with preferential G12/13 coupling, thrombin-stimulated PAR1 wildtype strongly induced RhoA-mediated stress fiber formation compared with mutant receptor. 26100877 0 36 theme N-linked 0:7 arg1 glycosylation 9:21 N-linked glycosylation 0:21 N-linked glycosylation of protease-activated receptor-1 at extracellular loop 2 0:78 N-linked glycosylation of protease-activated receptor-1 at extracellular loop 2 regulates G-protein signaling bias. 26100877 9 37 theme RhoA-mediated 1440:1452 arg1 formation 1467:1475 RhoA-mediated stress fiber formation 1440:1475 RhoA-mediated stress fiber formation 1440:1475 Consistent with preferential G12/13 coupling, thrombin-stimulated PAR1 wildtype strongly induced RhoA-mediated stress fiber formation compared with mutant receptor. 26100877 5 38 theme wildtype 846:853 arg1 receptor 855:862 glycosylated wildtype receptor 833:862 glycosylated wildtype receptor 833:862 A PAR1 mutant deficient in glycosylation at ECL2 was more effective at stimulating Gq-mediated phosphoinositide signaling compared with glycosylated wildtype receptor. 26100877 9 39 theme fiber 1461:1465 arg1 formation 1467:1475 RhoA-mediated stress fiber formation 1440:1475 RhoA-mediated stress fiber formation 1440:1475 Consistent with preferential G12/13 coupling, thrombin-stimulated PAR1 wildtype strongly induced RhoA-mediated stress fiber formation compared with mutant receptor. 26100877 10 40 theme Gq 1632:1633 arg1 signaling 1635:1643 Gq signaling 1632:1643 Gq signaling 1632:1643 In striking contrast, glycosylation-deficient PAR1 was more effective at increasing cellular proliferation, associated with Gq signaling, than wildtype receptor. 26100877 0 41 theme receptor-1 45:54 arg1 glycosylation 9:21 N-linked glycosylation 0:21 N-linked glycosylation of protease-activated receptor-1 at extracellular loop 2 0:78 N-linked glycosylation of protease-activated receptor-1 at extracellular loop 2 regulates G-protein signaling bias. 26100877 5 42 theme Gq-mediated 780:790 arg1 signaling 809:817 Gq-mediated phosphoinositide signaling 780:817 Gq-mediated phosphoinositide signaling 780:817 A PAR1 mutant deficient in glycosylation at ECL2 was more effective at stimulating Gq-mediated phosphoinositide signaling compared with glycosylated wildtype receptor. 26100877 6 43 theme wildtype 878:885 arg1 PAR1 887:890 wildtype PAR1 878:890 wildtype PAR1 878:890 In contrast, wildtype PAR1 displayed a greater efficacy at G12/13-dependent RhoA activation compared with mutant receptor lacking glycosylation at ECL2. 26100877 0 44 gly glycosylation 9:21 arg2 loop 73:76 extracellular loop 2 59:78 extracellular loop 2 59:78 N-linked glycosylation of protease-activated receptor-1 at extracellular loop 2 regulates G-protein signaling bias. 26100877 0 44 gly glycosylation 9:21 arg1 receptor-1 45:54 protease-activated receptor-1 26:54 protease-activated receptor-1 26:54 N-linked glycosylation of protease-activated receptor-1 at extracellular loop 2 regulates G-protein signaling bias. 26100877 0 44 gly glycosylation 9:21 arg1 loop 73:76 extracellular loop 2 59:78 extracellular loop 2 59:78 N-linked glycosylation of protease-activated receptor-1 at extracellular loop 2 regulates G-protein signaling bias. 26100877 3 45 theme multiple 490:497 arg1 subtypes 509:516 multiple G-protein subtypes 490:516 multiple G-protein subtypes 490:516 The molecular mechanism by which activation of a given GPCR with the same ligand permits coupling to multiple G-protein subtypes is unclear. 26100877 7 46 theme native 1206:1211 arg1 receptor 1213:1220 native receptor 1206:1220 native receptor 1206:1220 Endogenous PAR1 rendered deficient in glycosylation using tunicamycin, a glycoprotein synthesis inhibitor, also exhibited increased PI signaling and diminished RhoA activation opposite to native receptor. 26100877 9 47 theme mutant 1491:1496 arg1 receptor 1498:1505 mutant receptor 1491:1505 mutant receptor 1491:1505 Consistent with preferential G12/13 coupling, thrombin-stimulated PAR1 wildtype strongly induced RhoA-mediated stress fiber formation compared with mutant receptor. 26100877 10 48 theme wildtype 1651:1658 arg1 receptor 1660:1667 wildtype receptor 1651:1667 wildtype receptor 1651:1667 In striking contrast, glycosylation-deficient PAR1 was more effective at increasing cellular proliferation, associated with Gq signaling, than wildtype receptor. 26100877 11 49 theme N-linked 1884:1891 arg1 glycosylation 1893:1905 N-linked glycosylation 1884:1905 N-linked glycosylation of GPCRs 1884:1914 These studies suggest that N-linked glycosylation at ECL2 contributes to the stabilization of an active PAR1 state that preferentially couples to G12/13 versus Gq and defines a previously unidentified function for N-linked glycosylation of GPCRs in regulating G-protein signaling bias. 26100877 2 50 theme same 338:341 arg1 cell 343:346 the same cell 334:346 the same cell 334:346 Similar to other GPCRs, PAR1 is promiscuous and couples to multiple heterotrimeric G-protein subtypes in the same cell and promotes diverse cellular responses. 26100877 11 51 link N-linked 1697:1704 arg1 glycosylation 1706:1718 N-linked glycosylation 1697:1718 N-linked glycosylation at ECL2 1697:1726 These studies suggest that N-linked glycosylation at ECL2 contributes to the stabilization of an active PAR1 state that preferentially couples to G12/13 versus Gq and defines a previously unidentified function for N-linked glycosylation of GPCRs in regulating G-protein signaling bias. 26100877 11 52 theme PAR1 1774:1777 arg1 state 1779:1783 an active PAR1 state 1764:1783 an active PAR1 state that preferentially couples to G12/13 versus Gq and defines a previously unidentified function for N-linked glycosylation of GPCRs in regulating G-protein signaling bias 1764:1953 These studies suggest that N-linked glycosylation at ECL2 contributes to the stabilization of an active PAR1 state that preferentially couples to G12/13 versus Gq and defines a previously unidentified function for N-linked glycosylation of GPCRs in regulating G-protein signaling bias. 26100877 11 53 gly glycosylation 1706:1718 arg2 ECL2 1723:1726 ECL2 1723:1726 ECL2 1723:1726 These studies suggest that N-linked glycosylation at ECL2 contributes to the stabilization of an active PAR1 state that preferentially couples to G12/13 versus Gq and defines a previously unidentified function for N-linked glycosylation of GPCRs in regulating G-protein signaling bias. 26100877 11 53 gly glycosylation 1706:1718 arg1 state 1779:1783 an active PAR1 state 1764:1783 an active PAR1 state that preferentially couples to G12/13 versus Gq and defines a previously unidentified function for N-linked glycosylation of GPCRs in regulating G-protein signaling bias 1764:1953 These studies suggest that N-linked glycosylation at ECL2 contributes to the stabilization of an active PAR1 state that preferentially couples to G12/13 versus Gq and defines a previously unidentified function for N-linked glycosylation of GPCRs in regulating G-protein signaling bias. 26100877 11 53 gly glycosylation 1706:1718 arg1 ECL2 1723:1726 ECL2 1723:1726 ECL2 1723:1726 These studies suggest that N-linked glycosylation at ECL2 contributes to the stabilization of an active PAR1 state that preferentially couples to G12/13 versus Gq and defines a previously unidentified function for N-linked glycosylation of GPCRs in regulating G-protein signaling bias. 26100877 2 54 theme diverse 361:367 arg1 responses 378:386 diverse cellular responses 361:386 diverse cellular responses 361:386 Similar to other GPCRs, PAR1 is promiscuous and couples to multiple heterotrimeric G-protein subtypes in the same cell and promotes diverse cellular responses. 26100877 4 55 link N-linked 551:558 arg1 glycosylation 560:572 N-linked glycosylation 551:572 N-linked glycosylation of PAR1 at extracellular loop 2 (ECL2) 551:611 Here, we report that N-linked glycosylation of PAR1 at extracellular loop 2 (ECL2) controls G12/13 versus Gq coupling specificity in response to thrombin stimulation. 26100877 4 56 theme PAR1 577:580 arg1 glycosylation 560:572 N-linked glycosylation 551:572 N-linked glycosylation of PAR1 at extracellular loop 2 (ECL2) 551:611 Here, we report that N-linked glycosylation of PAR1 at extracellular loop 2 (ECL2) controls G12/13 versus Gq coupling specificity in response to thrombin stimulation. 26100877 10 57 theme striking 1511:1518 arg1 contrast 1520:1527 striking contrast 1511:1527 striking contrast 1511:1527 In striking contrast, glycosylation-deficient PAR1 was more effective at increasing cellular proliferation, associated with Gq signaling, than wildtype receptor. 26100877 2 58 theme multiple 288:295 arg1 subtypes 322:329 multiple heterotrimeric G-protein subtypes 288:329 multiple heterotrimeric G-protein subtypes in the same cell 288:346 Similar to other GPCRs, PAR1 is promiscuous and couples to multiple heterotrimeric G-protein subtypes in the same cell and promotes diverse cellular responses. 26100877 8 59 from coupling 1310:1317 arg1 effective 1297:1305 effective 1297:1305 effective 1297:1305 Remarkably, PAR1 wildtype and glycosylation-deficient mutant were equally effective at coupling to Gi and β-arrestin-1. 26100877 4 60 theme extracellular 585:597 arg1 loop 599:602 extracellular loop 2 585:604 extracellular loop 2 (ECL2) 585:611 Here, we report that N-linked glycosylation of PAR1 at extracellular loop 2 (ECL2) controls G12/13 versus Gq coupling specificity in response to thrombin stimulation. 26100877 4 60 theme extracellular 585:597 arg1 ECL2 607:610 ECL2 607:610 ECL2 607:610 Here, we report that N-linked glycosylation of PAR1 at extracellular loop 2 (ECL2) controls G12/13 versus Gq coupling specificity in response to thrombin stimulation. 26100877 8 61 theme PAR1 1235:1238 arg1 mutant 1277:1282 PAR1 wildtype and glycosylation-deficient mutant 1235:1282 PAR1 wildtype and glycosylation-deficient mutant 1235:1282 Remarkably, PAR1 wildtype and glycosylation-deficient mutant were equally effective at coupling to Gi and β-arrestin-1. 26100877 6 62 theme greater 904:910 arg1 efficacy 912:919 a greater efficacy 902:919 a greater efficacy at G12/13-dependent RhoA activation 902:955 In contrast, wildtype PAR1 displayed a greater efficacy at G12/13-dependent RhoA activation compared with mutant receptor lacking glycosylation at ECL2. 26100877 4 63 theme coupling 639:646 arg1 specificity 648:658 G12/13 versus Gq coupling specificity 622:658 specificity 648:658 Here, we report that N-linked glycosylation of PAR1 at extracellular loop 2 (ECL2) controls G12/13 versus Gq coupling specificity in response to thrombin stimulation. 26100877 7 64 theme increased 1140:1148 arg1 signaling 1153:1161 increased PI signaling 1140:1161 increased PI signaling 1140:1161 Endogenous PAR1 rendered deficient in glycosylation using tunicamycin, a glycoprotein synthesis inhibitor, also exhibited increased PI signaling and diminished RhoA activation opposite to native receptor. 26100877 10 65 from effective 1568:1576 arg1 contrast 1520:1527 striking contrast 1511:1527 striking contrast 1511:1527 In striking contrast, glycosylation-deficient PAR1 was more effective at increasing cellular proliferation, associated with Gq signaling, than wildtype receptor. 26100877 0 66 theme extracellular 59:71 arg1 loop 73:76 extracellular loop 2 59:78 extracellular loop 2 59:78 N-linked glycosylation of protease-activated receptor-1 at extracellular loop 2 regulates G-protein signaling bias. 26100877 7 67 from deficient 1043:1051 arg1 tunicamycin 1076:1086 glycosylation using tunicamycin 1056:1086 glycosylation using tunicamycin 1056:1086 Endogenous PAR1 rendered deficient in glycosylation using tunicamycin, a glycoprotein synthesis inhibitor, also exhibited increased PI signaling and diminished RhoA activation opposite to native receptor. 26100877 10 68 theme glycosylation-deficient 1530:1552 arg1 PAR1 1554:1557 glycosylation-deficient PAR1 1530:1557 glycosylation-deficient PAR1 1530:1557 In striking contrast, glycosylation-deficient PAR1 was more effective at increasing cellular proliferation, associated with Gq signaling, than wildtype receptor. 26100877 2 69 theme G-protein 312:320 arg1 subtypes 322:329 multiple heterotrimeric G-protein subtypes 288:329 multiple heterotrimeric G-protein subtypes in the same cell 288:346 Similar to other GPCRs, PAR1 is promiscuous and couples to multiple heterotrimeric G-protein subtypes in the same cell and promotes diverse cellular responses. 26100877 1 70 theme coagulant 200:208 arg1 thrombin 219:226 the coagulant protease thrombin 196:226 the coagulant protease thrombin 196:226 Protease-activated receptor-1 (PAR1) is a G-protein-coupled receptor (GPCR) for the coagulant protease thrombin. 26100877 5 71 from ECL2 741:744 arg1 glycosylation 724:736 glycosylation 724:736 glycosylation at ECL2 724:744 A PAR1 mutant deficient in glycosylation at ECL2 was more effective at stimulating Gq-mediated phosphoinositide signaling compared with glycosylated wildtype receptor. 26100877 11 72 theme N-linked 1697:1704 arg1 glycosylation 1706:1718 N-linked glycosylation 1697:1718 N-linked glycosylation at ECL2 1697:1726 These studies suggest that N-linked glycosylation at ECL2 contributes to the stabilization of an active PAR1 state that preferentially couples to G12/13 versus Gq and defines a previously unidentified function for N-linked glycosylation of GPCRs in regulating G-protein signaling bias. 26100877 7 73 from tunicamycin 1076:1086 arg1 deficient 1043:1051 deficient 1043:1051 deficient 1043:1051 Endogenous PAR1 rendered deficient in glycosylation using tunicamycin, a glycoprotein synthesis inhibitor, also exhibited increased PI signaling and diminished RhoA activation opposite to native receptor. 26100877 7 74 theme glycoprotein 1091:1102 arg1 PAR1 1029:1032 Endogenous PAR1 1018:1032 Endogenous PAR1 rendered deficient in glycosylation using tunicamycin 1018:1086 Endogenous PAR1 rendered deficient in glycosylation using tunicamycin, a glycoprotein synthesis inhibitor, also exhibited increased PI signaling and diminished RhoA activation opposite to native receptor. 26100877 7 74 theme glycoprotein 1091:1102 arg1 inhibitor 1114:1122 a glycoprotein synthesis inhibitor 1089:1122 a glycoprotein synthesis inhibitor 1089:1122 Endogenous PAR1 rendered deficient in glycosylation using tunicamycin, a glycoprotein synthesis inhibitor, also exhibited increased PI signaling and diminished RhoA activation opposite to native receptor. 26100877 5 75 from glycosylation 724:736 arg1 deficient 711:719 deficient 711:719 deficient 711:719 A PAR1 mutant deficient in glycosylation at ECL2 was more effective at stimulating Gq-mediated phosphoinositide signaling compared with glycosylated wildtype receptor. 26100877 6 76 theme mutant 971:976 arg1 receptor 978:985 mutant receptor 971:985 mutant receptor lacking glycosylation at ECL2 971:1015 In contrast, wildtype PAR1 displayed a greater efficacy at G12/13-dependent RhoA activation compared with mutant receptor lacking glycosylation at ECL2. 26100877 7 77 gly glycoprotein 1091:1102 arg1 glycoprotein 1091:1102 a glycoprotein synthesis inhibitor 1089:1122 a glycoprotein synthesis inhibitor 1089:1122 Endogenous PAR1 rendered deficient in glycosylation using tunicamycin, a glycoprotein synthesis inhibitor, also exhibited increased PI signaling and diminished RhoA activation opposite to native receptor. 26100877 7 78 theme glycosylation 1056:1068 arg1 tunicamycin 1076:1086 glycosylation using tunicamycin 1056:1086 glycosylation using tunicamycin 1056:1086 Endogenous PAR1 rendered deficient in glycosylation using tunicamycin, a glycoprotein synthesis inhibitor, also exhibited increased PI signaling and diminished RhoA activation opposite to native receptor. 26100877 9 79 theme preferential 1359:1370 arg1 coupling 1379:1386 preferential G12/13 coupling 1359:1386 preferential G12/13 coupling 1359:1386 Consistent with preferential G12/13 coupling, thrombin-stimulated PAR1 wildtype strongly induced RhoA-mediated stress fiber formation compared with mutant receptor. 26100877 0 80 theme signaling 100:108 arg1 bias 110:113 G-protein signaling bias 90:113 G-protein signaling bias 90:113 N-linked glycosylation of protease-activated receptor-1 at extracellular loop 2 regulates G-protein signaling bias. 26100877 4 81 from loop 599:602 arg1 glycosylation 560:572 N-linked glycosylation 551:572 N-linked glycosylation of PAR1 at extracellular loop 2 (ECL2) 551:611 Here, we report that N-linked glycosylation of PAR1 at extracellular loop 2 (ECL2) controls G12/13 versus Gq coupling specificity in response to thrombin stimulation. 26100877 9 82 theme thrombin-stimulated 1389:1407 arg1 PAR1 1409:1412 thrombin-stimulated PAR1 wildtype 1389:1421 thrombin-stimulated PAR1 wildtype 1389:1421 Consistent with preferential G12/13 coupling, thrombin-stimulated PAR1 wildtype strongly induced RhoA-mediated stress fiber formation compared with mutant receptor. 26100877 2 83 from subtypes 322:329 arg1 cell 343:346 the same cell 334:346 the same cell 334:346 Similar to other GPCRs, PAR1 is promiscuous and couples to multiple heterotrimeric G-protein subtypes in the same cell and promotes diverse cellular responses. 26100877 0 84 from loop 73:76 arg1 glycosylation 9:21 N-linked glycosylation 0:21 N-linked glycosylation of protease-activated receptor-1 at extracellular loop 2 0:78 N-linked glycosylation of protease-activated receptor-1 at extracellular loop 2 regulates G-protein signaling bias. 26100877 11 85 theme G-protein 1930:1938 arg1 bias 1950:1953 G-protein signaling bias 1930:1953 G-protein signaling bias 1930:1953 These studies suggest that N-linked glycosylation at ECL2 contributes to the stabilization of an active PAR1 state that preferentially couples to G12/13 versus Gq and defines a previously unidentified function for N-linked glycosylation of GPCRs in regulating G-protein signaling bias. 26100877 9 86 theme wildtype 1414:1421 arg1 PAR1 1409:1412 thrombin-stimulated PAR1 wildtype 1389:1421 thrombin-stimulated PAR1 wildtype 1389:1421 Consistent with preferential G12/13 coupling, thrombin-stimulated PAR1 wildtype strongly induced RhoA-mediated stress fiber formation compared with mutant receptor. 26100877 4 87 theme N-linked 551:558 arg1 glycosylation 560:572 N-linked glycosylation 551:572 N-linked glycosylation of PAR1 at extracellular loop 2 (ECL2) 551:611 Here, we report that N-linked glycosylation of PAR1 at extracellular loop 2 (ECL2) controls G12/13 versus Gq coupling specificity in response to thrombin stimulation. 26100877 10 88 theme cellular 1592:1599 arg1 proliferation 1601:1613 cellular proliferation 1592:1613 cellular proliferation 1592:1613 In striking contrast, glycosylation-deficient PAR1 was more effective at increasing cellular proliferation, associated with Gq signaling, than wildtype receptor. 26100877 3 89 theme given 438:442 arg1 GPCR 444:447 a given GPCR 436:447 a given GPCR 436:447 The molecular mechanism by which activation of a given GPCR with the same ligand permits coupling to multiple G-protein subtypes is unclear. 26100877 0 90 theme protease-activated 26:43 arg1 receptor-1 45:54 protease-activated receptor-1 26:54 protease-activated receptor-1 26:54 N-linked glycosylation of protease-activated receptor-1 at extracellular loop 2 regulates G-protein signaling bias. 26100877 9 91 theme stress 1454:1459 arg1 formation 1467:1475 RhoA-mediated stress fiber formation 1440:1475 RhoA-mediated stress fiber formation 1440:1475 Consistent with preferential G12/13 coupling, thrombin-stimulated PAR1 wildtype strongly induced RhoA-mediated stress fiber formation compared with mutant receptor. 26100877 1 92 theme Protease-activated 116:133 arg1 receptor 176:183 a G-protein-coupled receptor 156:183 a G-protein-coupled receptor (GPCR) for the coagulant protease thrombin 156:226 Protease-activated receptor-1 (PAR1) is a G-protein-coupled receptor (GPCR) for the coagulant protease thrombin. 26100877 1 92 theme Protease-activated 116:133 arg1 PAR1 147:150 PAR1 147:150 PAR1 147:150 Protease-activated receptor-1 (PAR1) is a G-protein-coupled receptor (GPCR) for the coagulant protease thrombin. 26100877 1 92 theme Protease-activated 116:133 arg1 receptor-1 135:144 Protease-activated receptor-1 116:144 Protease-activated receptor-1 (PAR1) 116:151 Protease-activated receptor-1 (PAR1) is a G-protein-coupled receptor (GPCR) for the coagulant protease thrombin. 26100877 11 93 gly glycosylation 1893:1905 arg1 GPCRs 1910:1914 GPCRs 1910:1914 GPCRs 1910:1914 These studies suggest that N-linked glycosylation at ECL2 contributes to the stabilization of an active PAR1 state that preferentially couples to G12/13 versus Gq and defines a previously unidentified function for N-linked glycosylation of GPCRs in regulating G-protein signaling bias. 26100877 3 94 theme same 458:461 arg1 ligand 463:468 the same ligand 454:468 the same ligand 454:468 The molecular mechanism by which activation of a given GPCR with the same ligand permits coupling to multiple G-protein subtypes is unclear. 26100877 5 95 theme phosphoinositide 792:807 arg1 signaling 809:817 Gq-mediated phosphoinositide signaling 780:817 Gq-mediated phosphoinositide signaling 780:817 A PAR1 mutant deficient in glycosylation at ECL2 was more effective at stimulating Gq-mediated phosphoinositide signaling compared with glycosylated wildtype receptor. 26100877 5 96 gly glycosylated 833:844 arg1 receptor 855:862 glycosylated wildtype receptor 833:862 glycosylated wildtype receptor 833:862 A PAR1 mutant deficient in glycosylation at ECL2 was more effective at stimulating Gq-mediated phosphoinositide signaling compared with glycosylated wildtype receptor. 26100877 3 97 theme G-protein 499:507 arg1 subtypes 509:516 multiple G-protein subtypes 490:516 multiple G-protein subtypes 490:516 The molecular mechanism by which activation of a given GPCR with the same ligand permits coupling to multiple G-protein subtypes is unclear. 26100877 10 98 from contrast 1520:1527 arg1 effective 1568:1576 effective 1568:1576 effective 1568:1576 In striking contrast, glycosylation-deficient PAR1 was more effective at increasing cellular proliferation, associated with Gq signaling, than wildtype receptor. 26100877 11 99 theme unidentified 1858:1869 arg1 function 1871:1878 a previously unidentified function 1845:1878 a previously unidentified function for N-linked glycosylation of GPCRs 1845:1914 These studies suggest that N-linked glycosylation at ECL2 contributes to the stabilization of an active PAR1 state that preferentially couples to G12/13 versus Gq and defines a previously unidentified function for N-linked glycosylation of GPCRs in regulating G-protein signaling bias. 26100877 11 100 theme active 1767:1772 arg1 state 1779:1783 an active PAR1 state 1764:1783 an active PAR1 state that preferentially couples to G12/13 versus Gq and defines a previously unidentified function for N-linked glycosylation of GPCRs in regulating G-protein signaling bias 1764:1953 These studies suggest that N-linked glycosylation at ECL2 contributes to the stabilization of an active PAR1 state that preferentially couples to G12/13 versus Gq and defines a previously unidentified function for N-linked glycosylation of GPCRs in regulating G-protein signaling bias. 26100877 11 101 link N-linked 1884:1891 arg1 glycosylation 1893:1905 N-linked glycosylation 1884:1905 N-linked glycosylation of GPCRs 1884:1914 These studies suggest that N-linked glycosylation at ECL2 contributes to the stabilization of an active PAR1 state that preferentially couples to G12/13 versus Gq and defines a previously unidentified function for N-linked glycosylation of GPCRs in regulating G-protein signaling bias. 26100877 2 102 theme cellular 369:376 arg1 responses 378:386 diverse cellular responses 361:386 diverse cellular responses 361:386 Similar to other GPCRs, PAR1 is promiscuous and couples to multiple heterotrimeric G-protein subtypes in the same cell and promotes diverse cellular responses. 25114108 8 0 theme type 1380:1383 arg1 strain 1420:1425 a strain 1418:1425 clinical and laboratory isolates of the North American type 1 and type 2 phylogenetic groups as well as a strain from Panama 1314:1437 Despite no apparent role in acute virulence in mice, secretion of the Cfp4 glycoprotein by yeast cells is consistent across clinical and laboratory isolates of the North American type 1 and type 2 phylogenetic groups as well as a strain from Panama. 25114108 8 0 theme type 1380:1383 arg1 isolates 1338:1345 clinical and laboratory isolates 1314:1345 clinical and laboratory isolates of the North American type 1 and type 2 phylogenetic groups as well as a strain from Panama 1314:1437 Despite no apparent role in acute virulence in mice, secretion of the Cfp4 glycoprotein by yeast cells is consistent across clinical and laboratory isolates of the North American type 1 and type 2 phylogenetic groups as well as a strain from Panama. 25114108 6 1 theme murine 954:959 arg1 model 961:965 a murine model 952:965 a murine model of histoplasmosis 952:983 Cfp4-deficient strains are not attenuated in virulence in human macrophages or during lung infection in a murine model of histoplasmosis. 25114108 7 2 theme Cfp4-deficient 1042:1055 arg1 strains 1057:1063 differentially marked Cfp4-producing and Cfp4-deficient strains 1001:1063 differentially marked Cfp4-producing and Cfp4-deficient strains 1001:1063 Coinfection of differentially marked Cfp4-producing and Cfp4-deficient strains demonstrates that production of Cfp4 does not confer a fitness advantage to Histoplasma yeasts during murine lung infection. 25114108 2 3 theme yeast 365:369 arg1 cells 371:375 Histoplasma yeast cells 353:375 Histoplasma yeast cells 353:375 Among the secreted proteome of Histoplasma, culture filtrate protein 4 (Cfp4) is a heavily glycosylated factor produced abundantly and specifically by Histoplasma yeast cells, suggesting its role in pathogenesis. 25114108 2 4 gly glycosylated 293:304 arg1 protein 263:269 culture filtrate protein 4 246:271 culture filtrate protein 4 (Cfp4) 246:278 Among the secreted proteome of Histoplasma, culture filtrate protein 4 (Cfp4) is a heavily glycosylated factor produced abundantly and specifically by Histoplasma yeast cells, suggesting its role in pathogenesis. 25114108 2 4 gly glycosylated 293:304 arg1 factor 306:311 a heavily glycosylated factor 283:311 a heavily glycosylated factor produced abundantly and specifically by Histoplasma yeast cells 283:375 Among the secreted proteome of Histoplasma, culture filtrate protein 4 (Cfp4) is a heavily glycosylated factor produced abundantly and specifically by Histoplasma yeast cells, suggesting its role in pathogenesis. 25114108 7 5 theme marked 1016:1021 arg1 strains 1057:1063 differentially marked Cfp4-producing and Cfp4-deficient strains 1001:1063 differentially marked Cfp4-producing and Cfp4-deficient strains 1001:1063 Coinfection of differentially marked Cfp4-producing and Cfp4-deficient strains demonstrates that production of Cfp4 does not confer a fitness advantage to Histoplasma yeasts during murine lung infection. 25114108 2 6 theme Histoplasma 353:363 arg1 cells 371:375 Histoplasma yeast cells 353:375 Histoplasma yeast cells 353:375 Among the secreted proteome of Histoplasma, culture filtrate protein 4 (Cfp4) is a heavily glycosylated factor produced abundantly and specifically by Histoplasma yeast cells, suggesting its role in pathogenesis. 25114108 9 7 theme human 1453:1457 arg1 sera 1466:1469 human immune sera 1453:1469 human immune sera 1453:1469 In addition, human immune sera recognize the Histoplasma Cfp4 protein, confirming Cfp4 production during infection of human hosts. 25114108 7 8 theme Cfp4-producing 1023:1036 arg1 strains 1057:1063 differentially marked Cfp4-producing and Cfp4-deficient strains 1001:1063 differentially marked Cfp4-producing and Cfp4-deficient strains 1001:1063 Coinfection of differentially marked Cfp4-producing and Cfp4-deficient strains demonstrates that production of Cfp4 does not confer a fitness advantage to Histoplasma yeasts during murine lung infection. 25114108 6 9 theme Cfp4-deficient 848:861 arg1 strains 863:869 Cfp4-deficient strains 848:869 Cfp4-deficient strains 848:869 Cfp4-deficient strains are not attenuated in virulence in human macrophages or during lung infection in a murine model of histoplasmosis. 25114108 3 10 dep epitope 532:538 arg1 each 540:543 each 540:543 each 540:543 We have generated three monoclonal antibodies as tools for characterization and detection of Cfp4 and determined the epitope each recognizes. 25114108 3 10 dep epitope 532:538 arg1 recognizes 545:554 recognizes 545:554 recognizes 545:554 We have generated three monoclonal antibodies as tools for characterization and detection of Cfp4 and determined the epitope each recognizes. 25114108 9 11 theme immune 1459:1464 arg1 sera 1466:1469 human immune sera 1453:1469 human immune sera 1453:1469 In addition, human immune sera recognize the Histoplasma Cfp4 protein, confirming Cfp4 production during infection of human hosts. 25114108 10 12 theme Cfp4 1618:1621 arg1 utility 1607:1613 the potential utility 1593:1613 the potential utility of Cfp4 as a diagnostic exoantigen for histoplasmosis 1593:1667 These results suggest the potential utility of Cfp4 as a diagnostic exoantigen for histoplasmosis. 25114108 8 13 theme phylogenetic 1387:1398 arg1 groups 1400:1405 phylogenetic groups 1387:1405 phylogenetic groups 1387:1405 Despite no apparent role in acute virulence in mice, secretion of the Cfp4 glycoprotein by yeast cells is consistent across clinical and laboratory isolates of the North American type 1 and type 2 phylogenetic groups as well as a strain from Panama. 25114108 8 14 theme American 1360:1367 arg1 type 1369:1372 the North American type 1 1350:1374 the North American type 1 1350:1374 Despite no apparent role in acute virulence in mice, secretion of the Cfp4 glycoprotein by yeast cells is consistent across clinical and laboratory isolates of the North American type 1 and type 2 phylogenetic groups as well as a strain from Panama. 25114108 6 15 from infection 939:947 arg1 model 961:965 a murine model 952:965 a murine model of histoplasmosis 952:983 Cfp4-deficient strains are not attenuated in virulence in human macrophages or during lung infection in a murine model of histoplasmosis. 25114108 6 16 theme lung 934:937 arg1 infection 939:947 lung infection 934:947 lung infection in a murine model of histoplasmosis 934:983 Cfp4-deficient strains are not attenuated in virulence in human macrophages or during lung infection in a murine model of histoplasmosis. 25114108 7 17 theme murine 1167:1172 arg1 infection 1179:1187 murine lung infection 1167:1187 murine lung infection 1167:1187 Coinfection of differentially marked Cfp4-producing and Cfp4-deficient strains demonstrates that production of Cfp4 does not confer a fitness advantage to Histoplasma yeasts during murine lung infection. 25114108 8 18 theme clinical 1314:1321 arg1 isolates 1338:1345 clinical and laboratory isolates 1314:1345 clinical and laboratory isolates of the North American type 1 and type 2 phylogenetic groups as well as a strain from Panama 1314:1437 Despite no apparent role in acute virulence in mice, secretion of the Cfp4 glycoprotein by yeast cells is consistent across clinical and laboratory isolates of the North American type 1 and type 2 phylogenetic groups as well as a strain from Panama. 25114108 1 19 theme dimorphic 175:183 arg1 pathogen 192:199 this thermally dimorphic fungal pathogen 160:199 this thermally dimorphic fungal pathogen 160:199 The yeast phase of Histoplasma capsulatum is the virulent form of this thermally dimorphic fungal pathogen. 25114108 5 20 theme RNA 830:832 arg1 interference 834:845 RNA interference 830:845 RNA interference 830:845 To test the function of Cfp4 in Histoplasma pathogenesis, we generated Cfp4-deficient strains by insertional mutagenesis and by RNA interference. 25114108 7 21 theme lung 1174:1177 arg1 infection 1179:1187 murine lung infection 1167:1187 murine lung infection 1167:1187 Coinfection of differentially marked Cfp4-producing and Cfp4-deficient strains demonstrates that production of Cfp4 does not confer a fitness advantage to Histoplasma yeasts during murine lung infection. 25114108 7 22 theme Histoplasma 1141:1151 arg1 yeasts 1153:1158 Histoplasma yeasts 1141:1158 Histoplasma yeasts 1141:1158 Coinfection of differentially marked Cfp4-producing and Cfp4-deficient strains demonstrates that production of Cfp4 does not confer a fitness advantage to Histoplasma yeasts during murine lung infection. 25114108 1 23 theme fungal 185:190 arg1 pathogen 192:199 this thermally dimorphic fungal pathogen 160:199 this thermally dimorphic fungal pathogen 160:199 The yeast phase of Histoplasma capsulatum is the virulent form of this thermally dimorphic fungal pathogen. 25114108 5 24 theme insertional 799:809 arg1 mutagenesis 811:821 insertional mutagenesis 799:821 insertional mutagenesis 799:821 To test the function of Cfp4 in Histoplasma pathogenesis, we generated Cfp4-deficient strains by insertional mutagenesis and by RNA interference. 25114108 10 25 theme potential 1597:1605 arg1 utility 1607:1613 the potential utility 1593:1613 the potential utility of Cfp4 as a diagnostic exoantigen for histoplasmosis 1593:1667 These results suggest the potential utility of Cfp4 as a diagnostic exoantigen for histoplasmosis. 25114108 1 26 theme yeast 98:102 arg1 phase 104:108 The yeast phase 94:108 The yeast phase of Histoplasma capsulatum 94:134 The yeast phase of Histoplasma capsulatum is the virulent form of this thermally dimorphic fungal pathogen. 25114108 1 26 theme yeast 98:102 arg1 form 152:155 the virulent form 139:155 the virulent form of this thermally dimorphic fungal pathogen 139:199 The yeast phase of Histoplasma capsulatum is the virulent form of this thermally dimorphic fungal pathogen. 25114108 8 27 from Panama 1432:1437 arg1 strain 1420:1425 a strain 1418:1425 clinical and laboratory isolates of the North American type 1 and type 2 phylogenetic groups as well as a strain from Panama 1314:1437 Despite no apparent role in acute virulence in mice, secretion of the Cfp4 glycoprotein by yeast cells is consistent across clinical and laboratory isolates of the North American type 1 and type 2 phylogenetic groups as well as a strain from Panama. 25114108 8 27 from Panama 1432:1437 arg1 isolates 1338:1345 clinical and laboratory isolates 1314:1345 clinical and laboratory isolates of the North American type 1 and type 2 phylogenetic groups as well as a strain from Panama 1314:1437 Despite no apparent role in acute virulence in mice, secretion of the Cfp4 glycoprotein by yeast cells is consistent across clinical and laboratory isolates of the North American type 1 and type 2 phylogenetic groups as well as a strain from Panama. 25114108 1 28 theme pathogen 192:199 arg1 phase 104:108 The yeast phase 94:108 The yeast phase of Histoplasma capsulatum 94:134 The yeast phase of Histoplasma capsulatum is the virulent form of this thermally dimorphic fungal pathogen. 25114108 1 28 theme pathogen 192:199 arg1 form 152:155 the virulent form 139:155 the virulent form of this thermally dimorphic fungal pathogen 139:199 The yeast phase of Histoplasma capsulatum is the virulent form of this thermally dimorphic fungal pathogen. 25114108 8 29 theme North 1354:1358 arg1 type 1369:1372 the North American type 1 1350:1374 the North American type 1 1350:1374 Despite no apparent role in acute virulence in mice, secretion of the Cfp4 glycoprotein by yeast cells is consistent across clinical and laboratory isolates of the North American type 1 and type 2 phylogenetic groups as well as a strain from Panama. 25114108 4 30 theme glycan 681:686 arg1 modification 688:699 N-linked glycan modification 672:699 N-linked glycan modification 672:699 Through site-directed mutagenesis of Cfp4, we identified three asparagines that function as the principal sites of N-linked glycan modification. 25114108 8 31 theme acute 1218:1222 arg1 virulence 1224:1232 acute virulence 1218:1232 acute virulence in mice 1218:1240 Despite no apparent role in acute virulence in mice, secretion of the Cfp4 glycoprotein by yeast cells is consistent across clinical and laboratory isolates of the North American type 1 and type 2 phylogenetic groups as well as a strain from Panama. 25114108 4 32 theme modification 688:699 arg1 sites 663:667 the principal sites 649:667 the principal sites of N-linked glycan modification 649:699 Through site-directed mutagenesis of Cfp4, we identified three asparagines that function as the principal sites of N-linked glycan modification. 25114108 4 32 theme modification 688:699 arg1 modification 688:699 N-linked glycan modification 672:699 N-linked glycan modification 672:699 Through site-directed mutagenesis of Cfp4, we identified three asparagines that function as the principal sites of N-linked glycan modification. 25114108 4 32 theme modification 688:699 arg1 asparagines 620:630 three asparagines 614:630 three asparagines that function as the principal sites of N-linked glycan modification 614:699 Through site-directed mutagenesis of Cfp4, we identified three asparagines that function as the principal sites of N-linked glycan modification. 25114108 8 33 theme Cfp4 1260:1263 arg1 glycoprotein 1265:1276 the Cfp4 glycoprotein 1256:1276 the Cfp4 glycoprotein 1256:1276 Despite no apparent role in acute virulence in mice, secretion of the Cfp4 glycoprotein by yeast cells is consistent across clinical and laboratory isolates of the North American type 1 and type 2 phylogenetic groups as well as a strain from Panama. 25114108 4 34 theme site-directed 565:577 arg1 mutagenesis 579:589 site-directed mutagenesis 565:589 site-directed mutagenesis of Cfp4 565:597 Through site-directed mutagenesis of Cfp4, we identified three asparagines that function as the principal sites of N-linked glycan modification. 25114108 8 35 gly glycoprotein 1265:1276 arg1 glycoprotein 1265:1276 the Cfp4 glycoprotein 1256:1276 the Cfp4 glycoprotein 1256:1276 Despite no apparent role in acute virulence in mice, secretion of the Cfp4 glycoprotein by yeast cells is consistent across clinical and laboratory isolates of the North American type 1 and type 2 phylogenetic groups as well as a strain from Panama. 25114108 2 36 theme glycosylated 293:304 arg1 protein 263:269 culture filtrate protein 4 246:271 culture filtrate protein 4 (Cfp4) 246:278 Among the secreted proteome of Histoplasma, culture filtrate protein 4 (Cfp4) is a heavily glycosylated factor produced abundantly and specifically by Histoplasma yeast cells, suggesting its role in pathogenesis. 25114108 2 36 theme glycosylated 293:304 arg1 factor 306:311 a heavily glycosylated factor 283:311 a heavily glycosylated factor produced abundantly and specifically by Histoplasma yeast cells 283:375 Among the secreted proteome of Histoplasma, culture filtrate protein 4 (Cfp4) is a heavily glycosylated factor produced abundantly and specifically by Histoplasma yeast cells, suggesting its role in pathogenesis. 25114108 2 37 theme culture 246:252 arg1 protein 263:269 culture filtrate protein 4 246:271 culture filtrate protein 4 (Cfp4) 246:278 Among the secreted proteome of Histoplasma, culture filtrate protein 4 (Cfp4) is a heavily glycosylated factor produced abundantly and specifically by Histoplasma yeast cells, suggesting its role in pathogenesis. 25114108 2 37 theme culture 246:252 arg1 Cfp4 274:277 Cfp4 274:277 Cfp4 274:277 Among the secreted proteome of Histoplasma, culture filtrate protein 4 (Cfp4) is a heavily glycosylated factor produced abundantly and specifically by Histoplasma yeast cells, suggesting its role in pathogenesis. 25114108 2 37 theme culture 246:252 arg1 factor 306:311 a heavily glycosylated factor 283:311 a heavily glycosylated factor produced abundantly and specifically by Histoplasma yeast cells 283:375 Among the secreted proteome of Histoplasma, culture filtrate protein 4 (Cfp4) is a heavily glycosylated factor produced abundantly and specifically by Histoplasma yeast cells, suggesting its role in pathogenesis. 25114108 4 38 theme principal 653:661 arg1 sites 663:667 the principal sites 649:667 the principal sites of N-linked glycan modification 649:699 Through site-directed mutagenesis of Cfp4, we identified three asparagines that function as the principal sites of N-linked glycan modification. 25114108 4 38 theme principal 653:661 arg1 modification 688:699 N-linked glycan modification 672:699 N-linked glycan modification 672:699 Through site-directed mutagenesis of Cfp4, we identified three asparagines that function as the principal sites of N-linked glycan modification. 25114108 4 38 theme principal 653:661 arg1 asparagines 620:630 three asparagines 614:630 three asparagines that function as the principal sites of N-linked glycan modification 614:699 Through site-directed mutagenesis of Cfp4, we identified three asparagines that function as the principal sites of N-linked glycan modification. 25114108 4 39 theme Cfp4 594:597 arg1 mutagenesis 579:589 site-directed mutagenesis 565:589 site-directed mutagenesis of Cfp4 565:597 Through site-directed mutagenesis of Cfp4, we identified three asparagines that function as the principal sites of N-linked glycan modification. 25114108 5 40 theme Cfp4 726:729 arg1 function 714:721 the function 710:721 the function of Cfp4 in Histoplasma pathogenesis 710:757 To test the function of Cfp4 in Histoplasma pathogenesis, we generated Cfp4-deficient strains by insertional mutagenesis and by RNA interference. 25114108 1 41 theme Histoplasma 113:123 arg1 capsulatum 125:134 Histoplasma capsulatum 113:134 Histoplasma capsulatum 113:134 The yeast phase of Histoplasma capsulatum is the virulent form of this thermally dimorphic fungal pathogen. 25114108 7 42 theme fitness 1120:1126 arg1 advantage 1128:1136 a fitness advantage 1118:1136 a fitness advantage to Histoplasma yeasts 1118:1158 Coinfection of differentially marked Cfp4-producing and Cfp4-deficient strains demonstrates that production of Cfp4 does not confer a fitness advantage to Histoplasma yeasts during murine lung infection. 25114108 6 43 theme human 906:910 arg1 macrophages 912:922 human macrophages 906:922 human macrophages 906:922 Cfp4-deficient strains are not attenuated in virulence in human macrophages or during lung infection in a murine model of histoplasmosis. 25114108 0 44 gly Glycosylation 0:12 arg1 yeast-phase 70:80 the Histoplasma capsulatum Cfp4 yeast-phase 38:80 the Histoplasma capsulatum Cfp4 yeast-phase 38:80 Glycosylation and immunoreactivity of the Histoplasma capsulatum Cfp4 yeast-phase exoantigen. 25114108 9 45 theme Cfp4 1497:1500 arg1 protein 1502:1508 the Histoplasma Cfp4 protein 1481:1508 the Histoplasma Cfp4 protein 1481:1508 In addition, human immune sera recognize the Histoplasma Cfp4 protein, confirming Cfp4 production during infection of human hosts. 25114108 3 46 theme monoclonal 439:448 arg1 tools 464:468 tools 464:468 tools for characterization and detection of Cfp4 464:511 We have generated three monoclonal antibodies as tools for characterization and detection of Cfp4 and determined the epitope each recognizes. 25114108 3 46 theme monoclonal 439:448 arg1 antibodies 450:459 three monoclonal antibodies 433:459 three monoclonal antibodies 433:459 We have generated three monoclonal antibodies as tools for characterization and detection of Cfp4 and determined the epitope each recognizes. 25114108 5 47 theme Histoplasma 734:744 arg1 pathogenesis 746:757 Histoplasma pathogenesis 734:757 Histoplasma pathogenesis 734:757 To test the function of Cfp4 in Histoplasma pathogenesis, we generated Cfp4-deficient strains by insertional mutagenesis and by RNA interference. 25114108 8 48 from role 1210:1213 arg1 virulence 1224:1232 acute virulence 1218:1232 acute virulence in mice 1218:1240 Despite no apparent role in acute virulence in mice, secretion of the Cfp4 glycoprotein by yeast cells is consistent across clinical and laboratory isolates of the North American type 1 and type 2 phylogenetic groups as well as a strain from Panama. 25114108 10 49 theme diagnostic 1628:1637 arg1 exoantigen 1639:1648 a diagnostic exoantigen 1626:1648 a diagnostic exoantigen for histoplasmosis 1626:1667 These results suggest the potential utility of Cfp4 as a diagnostic exoantigen for histoplasmosis. 25114108 9 50 theme Cfp4 1522:1525 arg1 production 1527:1536 Cfp4 production 1522:1536 Cfp4 production 1522:1536 In addition, human immune sera recognize the Histoplasma Cfp4 protein, confirming Cfp4 production during infection of human hosts. 25114108 0 51 theme Cfp4 65:68 arg1 yeast-phase 70:80 the Histoplasma capsulatum Cfp4 yeast-phase 38:80 the Histoplasma capsulatum Cfp4 yeast-phase 38:80 Glycosylation and immunoreactivity of the Histoplasma capsulatum Cfp4 yeast-phase exoantigen. 25114108 8 52 theme glycoprotein 1265:1276 arg1 secretion 1243:1251 secretion 1243:1251 secretion of the Cfp4 glycoprotein by yeast cells 1243:1291 Despite no apparent role in acute virulence in mice, secretion of the Cfp4 glycoprotein by yeast cells is consistent across clinical and laboratory isolates of the North American type 1 and type 2 phylogenetic groups as well as a strain from Panama. 25114108 8 53 theme apparent 1201:1208 arg1 role 1210:1213 no apparent role 1198:1213 no apparent role in acute virulence in mice 1198:1240 Despite no apparent role in acute virulence in mice, secretion of the Cfp4 glycoprotein by yeast cells is consistent across clinical and laboratory isolates of the North American type 1 and type 2 phylogenetic groups as well as a strain from Panama. 25114108 2 54 theme Histoplasma 233:243 arg1 proteome 221:228 the secreted proteome 208:228 the secreted proteome of Histoplasma 208:243 Among the secreted proteome of Histoplasma, culture filtrate protein 4 (Cfp4) is a heavily glycosylated factor produced abundantly and specifically by Histoplasma yeast cells, suggesting its role in pathogenesis. 25114108 7 55 theme Cfp4 1097:1100 arg1 production 1083:1092 production 1083:1092 production of Cfp4 1083:1100 Coinfection of differentially marked Cfp4-producing and Cfp4-deficient strains demonstrates that production of Cfp4 does not confer a fitness advantage to Histoplasma yeasts during murine lung infection. 25114108 1 56 theme capsulatum 125:134 arg1 phase 104:108 The yeast phase 94:108 The yeast phase of Histoplasma capsulatum 94:134 The yeast phase of Histoplasma capsulatum is the virulent form of this thermally dimorphic fungal pathogen. 25114108 1 56 theme capsulatum 125:134 arg1 form 152:155 the virulent form 139:155 the virulent form of this thermally dimorphic fungal pathogen 139:199 The yeast phase of Histoplasma capsulatum is the virulent form of this thermally dimorphic fungal pathogen. 25114108 0 57 theme capsulatum 54:63 arg1 yeast-phase 70:80 the Histoplasma capsulatum Cfp4 yeast-phase 38:80 the Histoplasma capsulatum Cfp4 yeast-phase 38:80 Glycosylation and immunoreactivity of the Histoplasma capsulatum Cfp4 yeast-phase exoantigen. 25114108 6 58 theme histoplasmosis 970:983 arg1 model 961:965 a murine model 952:965 a murine model of histoplasmosis 952:983 Cfp4-deficient strains are not attenuated in virulence in human macrophages or during lung infection in a murine model of histoplasmosis. 25114108 4 59 link N-linked 672:679 arg1 modification 688:699 N-linked glycan modification 672:699 N-linked glycan modification 672:699 Through site-directed mutagenesis of Cfp4, we identified three asparagines that function as the principal sites of N-linked glycan modification. 25114108 3 60 theme Cfp4 508:511 arg1 detection 495:503 detection 495:503 detection 495:503 We have generated three monoclonal antibodies as tools for characterization and detection of Cfp4 and determined the epitope each recognizes. 25114108 3 60 theme Cfp4 508:511 arg1 characterization 474:489 characterization 474:489 characterization 474:489 We have generated three monoclonal antibodies as tools for characterization and detection of Cfp4 and determined the epitope each recognizes. 25114108 2 61 theme secreted 212:219 arg1 proteome 221:228 the secreted proteome 208:228 the secreted proteome of Histoplasma 208:243 Among the secreted proteome of Histoplasma, culture filtrate protein 4 (Cfp4) is a heavily glycosylated factor produced abundantly and specifically by Histoplasma yeast cells, suggesting its role in pathogenesis. 25114108 8 62 dep type 1369:1372 arg1 groups 1400:1405 phylogenetic groups 1387:1405 phylogenetic groups 1387:1405 Despite no apparent role in acute virulence in mice, secretion of the Cfp4 glycoprotein by yeast cells is consistent across clinical and laboratory isolates of the North American type 1 and type 2 phylogenetic groups as well as a strain from Panama. 25114108 2 63 from role 393:396 arg1 pathogenesis 401:412 pathogenesis 401:412 pathogenesis 401:412 Among the secreted proteome of Histoplasma, culture filtrate protein 4 (Cfp4) is a heavily glycosylated factor produced abundantly and specifically by Histoplasma yeast cells, suggesting its role in pathogenesis. 25114108 8 64 theme type 1369:1372 arg1 strain 1420:1425 a strain 1418:1425 clinical and laboratory isolates of the North American type 1 and type 2 phylogenetic groups as well as a strain from Panama 1314:1437 Despite no apparent role in acute virulence in mice, secretion of the Cfp4 glycoprotein by yeast cells is consistent across clinical and laboratory isolates of the North American type 1 and type 2 phylogenetic groups as well as a strain from Panama. 25114108 8 64 theme type 1369:1372 arg1 isolates 1338:1345 clinical and laboratory isolates 1314:1345 clinical and laboratory isolates of the North American type 1 and type 2 phylogenetic groups as well as a strain from Panama 1314:1437 Despite no apparent role in acute virulence in mice, secretion of the Cfp4 glycoprotein by yeast cells is consistent across clinical and laboratory isolates of the North American type 1 and type 2 phylogenetic groups as well as a strain from Panama. 25114108 8 65 theme yeast 1281:1285 arg1 cells 1287:1291 yeast cells 1281:1291 yeast cells 1281:1291 Despite no apparent role in acute virulence in mice, secretion of the Cfp4 glycoprotein by yeast cells is consistent across clinical and laboratory isolates of the North American type 1 and type 2 phylogenetic groups as well as a strain from Panama. 25114108 7 66 theme strains 1057:1063 arg1 Coinfection 986:996 Coinfection 986:996 Coinfection of differentially marked Cfp4-producing and Cfp4-deficient strains 986:1063 Coinfection of differentially marked Cfp4-producing and Cfp4-deficient strains demonstrates that production of Cfp4 does not confer a fitness advantage to Histoplasma yeasts during murine lung infection. 25114108 1 67 theme virulent 143:150 arg1 phase 104:108 The yeast phase 94:108 The yeast phase of Histoplasma capsulatum 94:134 The yeast phase of Histoplasma capsulatum is the virulent form of this thermally dimorphic fungal pathogen. 25114108 1 67 theme virulent 143:150 arg1 form 152:155 the virulent form 139:155 the virulent form of this thermally dimorphic fungal pathogen 139:199 The yeast phase of Histoplasma capsulatum is the virulent form of this thermally dimorphic fungal pathogen. 25114108 5 68 from function 714:721 arg1 pathogenesis 746:757 Histoplasma pathogenesis 734:757 Histoplasma pathogenesis 734:757 To test the function of Cfp4 in Histoplasma pathogenesis, we generated Cfp4-deficient strains by insertional mutagenesis and by RNA interference. 25114108 5 69 theme Cfp4-deficient 773:786 arg1 strains 788:794 Cfp4-deficient strains 773:794 Cfp4-deficient strains 773:794 To test the function of Cfp4 in Histoplasma pathogenesis, we generated Cfp4-deficient strains by insertional mutagenesis and by RNA interference. 25114108 8 70 from virulence 1224:1232 arg1 mice 1237:1240 mice 1237:1240 mice 1237:1240 Despite no apparent role in acute virulence in mice, secretion of the Cfp4 glycoprotein by yeast cells is consistent across clinical and laboratory isolates of the North American type 1 and type 2 phylogenetic groups as well as a strain from Panama. 25114108 8 71 theme laboratory 1327:1336 arg1 isolates 1338:1345 clinical and laboratory isolates 1314:1345 clinical and laboratory isolates of the North American type 1 and type 2 phylogenetic groups as well as a strain from Panama 1314:1437 Despite no apparent role in acute virulence in mice, secretion of the Cfp4 glycoprotein by yeast cells is consistent across clinical and laboratory isolates of the North American type 1 and type 2 phylogenetic groups as well as a strain from Panama. 25114108 9 72 theme human 1558:1562 arg1 hosts 1564:1568 human hosts 1558:1568 human hosts 1558:1568 In addition, human immune sera recognize the Histoplasma Cfp4 protein, confirming Cfp4 production during infection of human hosts. 25114108 4 73 theme N-linked 672:679 arg1 modification 688:699 N-linked glycan modification 672:699 N-linked glycan modification 672:699 Through site-directed mutagenesis of Cfp4, we identified three asparagines that function as the principal sites of N-linked glycan modification. 25114108 0 74 theme yeast-phase 70:80 arg1 immunoreactivity 18:33 immunoreactivity 18:33 immunoreactivity 18:33 Glycosylation and immunoreactivity of the Histoplasma capsulatum Cfp4 yeast-phase exoantigen. 25114108 0 74 theme yeast-phase 70:80 arg1 Glycosylation 0:12 Glycosylation 0:12 Glycosylation 0:12 Glycosylation and immunoreactivity of the Histoplasma capsulatum Cfp4 yeast-phase exoantigen. 25114108 9 75 theme Histoplasma 1485:1495 arg1 protein 1502:1508 the Histoplasma Cfp4 protein 1481:1508 the Histoplasma Cfp4 protein 1481:1508 In addition, human immune sera recognize the Histoplasma Cfp4 protein, confirming Cfp4 production during infection of human hosts. 25114108 2 76 theme filtrate 254:261 arg1 protein 263:269 culture filtrate protein 4 246:271 culture filtrate protein 4 (Cfp4) 246:278 Among the secreted proteome of Histoplasma, culture filtrate protein 4 (Cfp4) is a heavily glycosylated factor produced abundantly and specifically by Histoplasma yeast cells, suggesting its role in pathogenesis. 25114108 2 76 theme filtrate 254:261 arg1 Cfp4 274:277 Cfp4 274:277 Cfp4 274:277 Among the secreted proteome of Histoplasma, culture filtrate protein 4 (Cfp4) is a heavily glycosylated factor produced abundantly and specifically by Histoplasma yeast cells, suggesting its role in pathogenesis. 25114108 2 76 theme filtrate 254:261 arg1 factor 306:311 a heavily glycosylated factor 283:311 a heavily glycosylated factor produced abundantly and specifically by Histoplasma yeast cells 283:375 Among the secreted proteome of Histoplasma, culture filtrate protein 4 (Cfp4) is a heavily glycosylated factor produced abundantly and specifically by Histoplasma yeast cells, suggesting its role in pathogenesis. 25114108 9 77 theme hosts 1564:1568 arg1 infection 1545:1553 infection 1545:1553 infection of human hosts 1545:1568 In addition, human immune sera recognize the Histoplasma Cfp4 protein, confirming Cfp4 production during infection of human hosts. 26980729 5 0 from inhibition 967:976 arg1 Golgi 1002:1006 the Golgi 998:1006 the Golgi 998:1006 Tunicamycin inhibition of glycosylation in the endoplasmic reticulum or mutation of the Asn-24 glycosylation site decreased GC activity, but neither inhibition of glycosylation in the Golgi by N-acetylglucosaminyltransferase I gene inactivation nor PNGase F deglycosylation of fully processed GC-B reduced GC activity. 26980729 1 1 theme receptor 253:260 arg1 B 262:262 natriuretic peptide receptor B 233:262 natriuretic peptide receptor B 233:262 C-type natriuretic peptide activation of guanylyl cyclase B (GC-B), also known as natriuretic peptide receptor B or NPR2, stimulates long bone growth, and missense mutations in GC-B cause dwarfism. 26980729 2 2 theme natriuretic 420:430 arg1 peptide 432:438 (125)I-C-type natriuretic peptide 406:438 (125)I-C-type natriuretic peptide 406:438 Four such mutants (L658F, Y708C, R776W, and G959A) bound (125)I-C-type natriuretic peptide on the surface of cells but failed to synthesize cGMP in membrane GC assays. 26980729 3 3 theme mutant 571:576 arg1 receptors 578:586 the mutant receptors 567:586 the mutant receptors 567:586 Immunofluorescence microscopy also indicated that the mutant receptors were on the cell surface. 26980729 5 4 theme N-acetylglucosaminyltransferase 1011:1041 arg1 inactivation 1050:1061 N-acetylglucosaminyltransferase I gene inactivation 1011:1061 N-acetylglucosaminyltransferase I gene inactivation 1011:1061 Tunicamycin inhibition of glycosylation in the endoplasmic reticulum or mutation of the Asn-24 glycosylation site decreased GC activity, but neither inhibition of glycosylation in the Golgi by N-acetylglucosaminyltransferase I gene inactivation nor PNGase F deglycosylation of fully processed GC-B reduced GC activity. 26980729 5 5 theme glycosylation 981:993 arg1 inhibition 967:976 inhibition 967:976 inhibition of glycosylation in the Golgi by N-acetylglucosaminyltransferase I gene inactivation 967:1061 Tunicamycin inhibition of glycosylation in the endoplasmic reticulum or mutation of the Asn-24 glycosylation site decreased GC activity, but neither inhibition of glycosylation in the Golgi by N-acetylglucosaminyltransferase I gene inactivation nor PNGase F deglycosylation of fully processed GC-B reduced GC activity. 26980729 2 6 theme cells 458:462 arg1 surface 447:453 the surface 443:453 the surface of cells 443:462 Four such mutants (L658F, Y708C, R776W, and G959A) bound (125)I-C-type natriuretic peptide on the surface of cells but failed to synthesize cGMP in membrane GC assays. 26980729 5 7 theme processed 1101:1109 arg1 GC-B 1111:1114 fully processed GC-B 1095:1114 fully processed GC-B 1095:1114 Tunicamycin inhibition of glycosylation in the endoplasmic reticulum or mutation of the Asn-24 glycosylation site decreased GC activity, but neither inhibition of glycosylation in the Golgi by N-acetylglucosaminyltransferase I gene inactivation nor PNGase F deglycosylation of fully processed GC-B reduced GC activity. 26980729 5 8 theme glycosylation 913:925 arg1 site 927:930 the Asn-24 glycosylation site 902:930 the Asn-24 glycosylation site 902:930 Tunicamycin inhibition of glycosylation in the endoplasmic reticulum or mutation of the Asn-24 glycosylation site decreased GC activity, but neither inhibition of glycosylation in the Golgi by N-acetylglucosaminyltransferase I gene inactivation nor PNGase F deglycosylation of fully processed GC-B reduced GC activity. 26980729 5 9 theme GC-B 1111:1114 arg1 deglycosylation 1076:1090 PNGase F deglycosylation 1067:1090 PNGase F deglycosylation of fully processed GC-B 1067:1114 Tunicamycin inhibition of glycosylation in the endoplasmic reticulum or mutation of the Asn-24 glycosylation site decreased GC activity, but neither inhibition of glycosylation in the Golgi by N-acetylglucosaminyltransferase I gene inactivation nor PNGase F deglycosylation of fully processed GC-B reduced GC activity. 26980729 1 10 theme guanylyl 192:199 arg1 cyclase 201:207 guanylyl cyclase B (GC-B) 192:216 guanylyl cyclase B (GC-B) 192:216 C-type natriuretic peptide activation of guanylyl cyclase B (GC-B), also known as natriuretic peptide receptor B or NPR2, stimulates long bone growth, and missense mutations in GC-B cause dwarfism. 26980729 5 11 gly glycosylation 981:993 arg1 Golgi 1002:1006 the Golgi 998:1006 the Golgi 998:1006 Tunicamycin inhibition of glycosylation in the endoplasmic reticulum or mutation of the Asn-24 glycosylation site decreased GC activity, but neither inhibition of glycosylation in the Golgi by N-acetylglucosaminyltransferase I gene inactivation nor PNGase F deglycosylation of fully processed GC-B reduced GC activity. 26980729 6 12 gly glycosylation 1185:1197 arg1 domain 1276:1281 ligand-binding domain 1261:1281 ligand-binding domain 1261:1281 We conclude that endoplasmic reticulum-mediated glycosylation is required for the formation of an active catalytic, but not ligand-binding domain, and that mutations that inhibit this process cause dwarfism. 26980729 6 12 gly glycosylation 1185:1197 arg1 catalytic 1242:1250 catalytic 1242:1250 catalytic 1242:1250 We conclude that endoplasmic reticulum-mediated glycosylation is required for the formation of an active catalytic, but not ligand-binding domain, and that mutations that inhibit this process cause dwarfism. 26980729 1 13 theme cyclase 201:207 arg1 activation 178:187 C-type natriuretic peptide activation 151:187 C-type natriuretic peptide activation 151:187 C-type natriuretic peptide activation of guanylyl cyclase B (GC-B), also known as natriuretic peptide receptor B or NPR2, stimulates long bone growth, and missense mutations in GC-B cause dwarfism. 26980729 0 14 theme Active 14:19 arg1 B 38:38 Catalytically Active Guanylyl Cyclase B 0:38 Catalytically Active Guanylyl Cyclase B 0:38 Catalytically Active Guanylyl Cyclase B Requires Endoplasmic Reticulum-mediated Glycosylation, and Mutations That Inhibit This Process Cause Dwarfism. 26980729 5 15 theme GC 1124:1125 arg1 activity 1127:1134 GC activity 1124:1134 GC activity 1124:1134 Tunicamycin inhibition of glycosylation in the endoplasmic reticulum or mutation of the Asn-24 glycosylation site decreased GC activity, but neither inhibition of glycosylation in the Golgi by N-acetylglucosaminyltransferase I gene inactivation nor PNGase F deglycosylation of fully processed GC-B reduced GC activity. 26980729 6 16 theme domain 1276:1281 arg1 formation 1219:1227 the formation 1215:1227 the formation of an active catalytic, but not ligand-binding domain 1215:1281 We conclude that endoplasmic reticulum-mediated glycosylation is required for the formation of an active catalytic, but not ligand-binding domain, and that mutations that inhibit this process cause dwarfism. 26980729 5 17 theme site 927:930 arg1 mutation 890:897 mutation 890:897 mutation of the Asn-24 glycosylation site 890:930 Tunicamycin inhibition of glycosylation in the endoplasmic reticulum or mutation of the Asn-24 glycosylation site decreased GC activity, but neither inhibition of glycosylation in the Golgi by N-acetylglucosaminyltransferase I gene inactivation nor PNGase F deglycosylation of fully processed GC-B reduced GC activity. 26980729 5 17 theme site 927:930 arg1 reticulum 877:885 the endoplasmic reticulum 861:885 the endoplasmic reticulum 861:885 Tunicamycin inhibition of glycosylation in the endoplasmic reticulum or mutation of the Asn-24 glycosylation site decreased GC activity, but neither inhibition of glycosylation in the Golgi by N-acetylglucosaminyltransferase I gene inactivation nor PNGase F deglycosylation of fully processed GC-B reduced GC activity. 26980729 5 18 from glycosylation 981:993 arg1 Golgi 1002:1006 the Golgi 998:1006 the Golgi 998:1006 Tunicamycin inhibition of glycosylation in the endoplasmic reticulum or mutation of the Asn-24 glycosylation site decreased GC activity, but neither inhibition of glycosylation in the Golgi by N-acetylglucosaminyltransferase I gene inactivation nor PNGase F deglycosylation of fully processed GC-B reduced GC activity. 26980729 5 19 gly glycosylation 913:925 arg2 site 927:930 the Asn-24 glycosylation site 902:930 the Asn-24 glycosylation site 902:930 Tunicamycin inhibition of glycosylation in the endoplasmic reticulum or mutation of the Asn-24 glycosylation site decreased GC activity, but neither inhibition of glycosylation in the Golgi by N-acetylglucosaminyltransferase I gene inactivation nor PNGase F deglycosylation of fully processed GC-B reduced GC activity. 26980729 6 20 theme ligand-binding 1261:1274 arg1 domain 1276:1281 ligand-binding domain 1261:1281 ligand-binding domain 1261:1281 We conclude that endoplasmic reticulum-mediated glycosylation is required for the formation of an active catalytic, but not ligand-binding domain, and that mutations that inhibit this process cause dwarfism. 26980729 5 21 theme gene 1045:1048 arg1 inactivation 1050:1061 N-acetylglucosaminyltransferase I gene inactivation 1011:1061 N-acetylglucosaminyltransferase I gene inactivation 1011:1061 Tunicamycin inhibition of glycosylation in the endoplasmic reticulum or mutation of the Asn-24 glycosylation site decreased GC activity, but neither inhibition of glycosylation in the Golgi by N-acetylglucosaminyltransferase I gene inactivation nor PNGase F deglycosylation of fully processed GC-B reduced GC activity. 26980729 0 22 theme Cyclase 30:36 arg1 B 38:38 Catalytically Active Guanylyl Cyclase B 0:38 Catalytically Active Guanylyl Cyclase B 0:38 Catalytically Active Guanylyl Cyclase B Requires Endoplasmic Reticulum-mediated Glycosylation, and Mutations That Inhibit This Process Cause Dwarfism. 26980729 3 23 theme Immunofluorescence 517:534 arg1 microscopy 536:545 Immunofluorescence microscopy 517:545 Immunofluorescence microscopy 517:545 Immunofluorescence microscopy also indicated that the mutant receptors were on the cell surface. 26980729 5 24 theme GC 942:943 arg1 activity 945:952 GC activity 942:952 GC activity 942:952 Tunicamycin inhibition of glycosylation in the endoplasmic reticulum or mutation of the Asn-24 glycosylation site decreased GC activity, but neither inhibition of glycosylation in the Golgi by N-acetylglucosaminyltransferase I gene inactivation nor PNGase F deglycosylation of fully processed GC-B reduced GC activity. 26980729 0 25 theme Guanylyl 21:28 arg1 B 38:38 Catalytically Active Guanylyl Cyclase B 0:38 Catalytically Active Guanylyl Cyclase B 0:38 Catalytically Active Guanylyl Cyclase B Requires Endoplasmic Reticulum-mediated Glycosylation, and Mutations That Inhibit This Process Cause Dwarfism. 26980729 1 26 theme long 284:287 arg1 growth 294:299 long bone growth 284:299 long bone growth 284:299 C-type natriuretic peptide activation of guanylyl cyclase B (GC-B), also known as natriuretic peptide receptor B or NPR2, stimulates long bone growth, and missense mutations in GC-B cause dwarfism. 26980729 5 27 theme F 1074:1074 arg1 deglycosylation 1076:1090 PNGase F deglycosylation 1067:1090 PNGase F deglycosylation of fully processed GC-B 1067:1114 Tunicamycin inhibition of glycosylation in the endoplasmic reticulum or mutation of the Asn-24 glycosylation site decreased GC activity, but neither inhibition of glycosylation in the Golgi by N-acetylglucosaminyltransferase I gene inactivation nor PNGase F deglycosylation of fully processed GC-B reduced GC activity. 26980729 5 28 from Golgi 1002:1006 arg1 inhibition 967:976 inhibition 967:976 inhibition of glycosylation in the Golgi by N-acetylglucosaminyltransferase I gene inactivation 967:1061 Tunicamycin inhibition of glycosylation in the endoplasmic reticulum or mutation of the Asn-24 glycosylation site decreased GC activity, but neither inhibition of glycosylation in the Golgi by N-acetylglucosaminyltransferase I gene inactivation nor PNGase F deglycosylation of fully processed GC-B reduced GC activity. 26980729 2 29 theme such 354:357 arg1 L658F 368:372 L658F 368:372 L658F 368:372 Four such mutants (L658F, Y708C, R776W, and G959A) bound (125)I-C-type natriuretic peptide on the surface of cells but failed to synthesize cGMP in membrane GC assays. 26980729 2 29 theme such 354:357 arg1 mutants 359:365 Four such mutants 349:365 Four such mutants (L658F, Y708C, R776W, and G959A) 349:398 Four such mutants (L658F, Y708C, R776W, and G959A) bound (125)I-C-type natriuretic peptide on the surface of cells but failed to synthesize cGMP in membrane GC assays. 26980729 2 29 theme such 354:357 arg1 R776W 382:386 R776W 382:386 R776W 382:386 Four such mutants (L658F, Y708C, R776W, and G959A) bound (125)I-C-type natriuretic peptide on the surface of cells but failed to synthesize cGMP in membrane GC assays. 26980729 2 29 theme such 354:357 arg1 G959A 393:397 G959A 393:397 G959A 393:397 Four such mutants (L658F, Y708C, R776W, and G959A) bound (125)I-C-type natriuretic peptide on the surface of cells but failed to synthesize cGMP in membrane GC assays. 26980729 2 29 theme such 354:357 arg1 Y708C 375:379 Y708C 375:379 Y708C 375:379 Four such mutants (L658F, Y708C, R776W, and G959A) bound (125)I-C-type natriuretic peptide on the surface of cells but failed to synthesize cGMP in membrane GC assays. 26980729 2 30 theme I-C-type 411:418 arg1 peptide 432:438 (125)I-C-type natriuretic peptide 406:438 (125)I-C-type natriuretic peptide 406:438 Four such mutants (L658F, Y708C, R776W, and G959A) bound (125)I-C-type natriuretic peptide on the surface of cells but failed to synthesize cGMP in membrane GC assays. 26980729 1 31 theme bone 289:292 arg1 growth 294:299 long bone growth 284:299 long bone growth 284:299 C-type natriuretic peptide activation of guanylyl cyclase B (GC-B), also known as natriuretic peptide receptor B or NPR2, stimulates long bone growth, and missense mutations in GC-B cause dwarfism. 26980729 4 32 gly glycosylated 673:684 arg1 proteins 625:632 All mutant proteins 614:632 All mutant proteins 614:632 All mutant proteins were dephosphorylated and incompletely glycosylated, but dephosphorylation did not explain the inactivation because the mutations inactivated a "constitutively phosphorylated" enzyme. 26980729 5 33 theme Tunicamycin 818:828 arg1 inhibition 830:839 Tunicamycin inhibition 818:839 Tunicamycin inhibition of glycosylation in the endoplasmic reticulum or mutation of the Asn-24 glycosylation site 818:930 Tunicamycin inhibition of glycosylation in the endoplasmic reticulum or mutation of the Asn-24 glycosylation site decreased GC activity, but neither inhibition of glycosylation in the Golgi by N-acetylglucosaminyltransferase I gene inactivation nor PNGase F deglycosylation of fully processed GC-B reduced GC activity. 26980729 6 34 theme reticulum-mediated 1166:1183 arg1 glycosylation 1185:1197 endoplasmic reticulum-mediated glycosylation 1154:1197 endoplasmic reticulum-mediated glycosylation 1154:1197 We conclude that endoplasmic reticulum-mediated glycosylation is required for the formation of an active catalytic, but not ligand-binding domain, and that mutations that inhibit this process cause dwarfism. 26980729 0 35 theme Reticulum-mediated 61:78 arg1 Glycosylation 80:92 Endoplasmic Reticulum-mediated Glycosylation 49:92 Endoplasmic Reticulum-mediated Glycosylation 49:92 Catalytically Active Guanylyl Cyclase B Requires Endoplasmic Reticulum-mediated Glycosylation, and Mutations That Inhibit This Process Cause Dwarfism. 26980729 5 36 theme endoplasmic 865:875 arg1 reticulum 877:885 the endoplasmic reticulum 861:885 the endoplasmic reticulum 861:885 Tunicamycin inhibition of glycosylation in the endoplasmic reticulum or mutation of the Asn-24 glycosylation site decreased GC activity, but neither inhibition of glycosylation in the Golgi by N-acetylglucosaminyltransferase I gene inactivation nor PNGase F deglycosylation of fully processed GC-B reduced GC activity. 26980729 4 37 theme phosphorylated 794:807 arg1 " 808:808 a "constitutively phosphorylated" 776:808 a "constitutively phosphorylated" enzyme 776:815 All mutant proteins were dephosphorylated and incompletely glycosylated, but dephosphorylation did not explain the inactivation because the mutations inactivated a "constitutively phosphorylated" enzyme. 26980729 4 38 theme " 808:808 arg1 enzyme 810:815 a "constitutively phosphorylated" enzyme 776:815 a "constitutively phosphorylated" enzyme 776:815 All mutant proteins were dephosphorylated and incompletely glycosylated, but dephosphorylation did not explain the inactivation because the mutations inactivated a "constitutively phosphorylated" enzyme. 26980729 5 39 from inhibition 830:839 arg1 mutation 890:897 mutation 890:897 mutation of the Asn-24 glycosylation site 890:930 Tunicamycin inhibition of glycosylation in the endoplasmic reticulum or mutation of the Asn-24 glycosylation site decreased GC activity, but neither inhibition of glycosylation in the Golgi by N-acetylglucosaminyltransferase I gene inactivation nor PNGase F deglycosylation of fully processed GC-B reduced GC activity. 26980729 5 39 from inhibition 830:839 arg1 reticulum 877:885 the endoplasmic reticulum 861:885 the endoplasmic reticulum 861:885 Tunicamycin inhibition of glycosylation in the endoplasmic reticulum or mutation of the Asn-24 glycosylation site decreased GC activity, but neither inhibition of glycosylation in the Golgi by N-acetylglucosaminyltransferase I gene inactivation nor PNGase F deglycosylation of fully processed GC-B reduced GC activity. 26980729 0 40 theme Endoplasmic 49:59 arg1 Glycosylation 80:92 Endoplasmic Reticulum-mediated Glycosylation 49:92 Endoplasmic Reticulum-mediated Glycosylation 49:92 Catalytically Active Guanylyl Cyclase B Requires Endoplasmic Reticulum-mediated Glycosylation, and Mutations That Inhibit This Process Cause Dwarfism. 26980729 2 41 theme GC 506:507 arg1 assays 509:514 membrane GC assays 497:514 membrane GC assays 497:514 Four such mutants (L658F, Y708C, R776W, and G959A) bound (125)I-C-type natriuretic peptide on the surface of cells but failed to synthesize cGMP in membrane GC assays. 26980729 5 42 theme I 1043:1043 arg1 inactivation 1050:1061 N-acetylglucosaminyltransferase I gene inactivation 1011:1061 N-acetylglucosaminyltransferase I gene inactivation 1011:1061 Tunicamycin inhibition of glycosylation in the endoplasmic reticulum or mutation of the Asn-24 glycosylation site decreased GC activity, but neither inhibition of glycosylation in the Golgi by N-acetylglucosaminyltransferase I gene inactivation nor PNGase F deglycosylation of fully processed GC-B reduced GC activity. 26980729 1 43 dep cyclase 201:207 arg1 B 209:209 B 209:209 guanylyl cyclase B (GC-B) 192:216 C-type natriuretic peptide activation of guanylyl cyclase B (GC-B), also known as natriuretic peptide receptor B or NPR2, stimulates long bone growth, and missense mutations in GC-B cause dwarfism. 26980729 1 43 dep cyclase 201:207 arg1 GC-B 212:215 GC-B 212:215 GC-B 212:215 C-type natriuretic peptide activation of guanylyl cyclase B (GC-B), also known as natriuretic peptide receptor B or NPR2, stimulates long bone growth, and missense mutations in GC-B cause dwarfism. 26980729 5 44 gly deglycosylation 1076:1090 arg1 GC-B 1111:1114 fully processed GC-B 1095:1114 fully processed GC-B 1095:1114 Tunicamycin inhibition of glycosylation in the endoplasmic reticulum or mutation of the Asn-24 glycosylation site decreased GC activity, but neither inhibition of glycosylation in the Golgi by N-acetylglucosaminyltransferase I gene inactivation nor PNGase F deglycosylation of fully processed GC-B reduced GC activity. 26980729 1 45 theme missense 306:313 arg1 mutations 315:323 missense mutations 306:323 missense mutations in GC-B 306:331 C-type natriuretic peptide activation of guanylyl cyclase B (GC-B), also known as natriuretic peptide receptor B or NPR2, stimulates long bone growth, and missense mutations in GC-B cause dwarfism. 26980729 2 46 theme membrane 497:504 arg1 assays 509:514 membrane GC assays 497:514 membrane GC assays 497:514 Four such mutants (L658F, Y708C, R776W, and G959A) bound (125)I-C-type natriuretic peptide on the surface of cells but failed to synthesize cGMP in membrane GC assays. 26980729 4 47 theme mutant 618:623 arg1 proteins 625:632 All mutant proteins 614:632 All mutant proteins 614:632 All mutant proteins were dephosphorylated and incompletely glycosylated, but dephosphorylation did not explain the inactivation because the mutations inactivated a "constitutively phosphorylated" enzyme. 26980729 5 48 theme Asn-24 906:911 arg1 site 927:930 the Asn-24 glycosylation site 902:930 the Asn-24 glycosylation site 902:930 Tunicamycin inhibition of glycosylation in the endoplasmic reticulum or mutation of the Asn-24 glycosylation site decreased GC activity, but neither inhibition of glycosylation in the Golgi by N-acetylglucosaminyltransferase I gene inactivation nor PNGase F deglycosylation of fully processed GC-B reduced GC activity. 26980729 6 49 theme endoplasmic 1154:1164 arg1 glycosylation 1185:1197 endoplasmic reticulum-mediated glycosylation 1154:1197 endoplasmic reticulum-mediated glycosylation 1154:1197 We conclude that endoplasmic reticulum-mediated glycosylation is required for the formation of an active catalytic, but not ligand-binding domain, and that mutations that inhibit this process cause dwarfism. 26980729 3 50 theme cell 600:603 arg1 surface 605:611 the cell surface 596:611 the cell surface 596:611 Immunofluorescence microscopy also indicated that the mutant receptors were on the cell surface. 26980729 2 51 dep mutants 359:365 arg1 L658F 368:372 L658F 368:372 L658F 368:372 Four such mutants (L658F, Y708C, R776W, and G959A) bound (125)I-C-type natriuretic peptide on the surface of cells but failed to synthesize cGMP in membrane GC assays. 26980729 2 51 dep mutants 359:365 arg1 mutants 359:365 Four such mutants 349:365 Four such mutants (L658F, Y708C, R776W, and G959A) 349:398 Four such mutants (L658F, Y708C, R776W, and G959A) bound (125)I-C-type natriuretic peptide on the surface of cells but failed to synthesize cGMP in membrane GC assays. 26980729 2 51 dep mutants 359:365 arg1 R776W 382:386 R776W 382:386 R776W 382:386 Four such mutants (L658F, Y708C, R776W, and G959A) bound (125)I-C-type natriuretic peptide on the surface of cells but failed to synthesize cGMP in membrane GC assays. 26980729 2 51 dep mutants 359:365 arg1 G959A 393:397 G959A 393:397 G959A 393:397 Four such mutants (L658F, Y708C, R776W, and G959A) bound (125)I-C-type natriuretic peptide on the surface of cells but failed to synthesize cGMP in membrane GC assays. 26980729 2 51 dep mutants 359:365 arg1 Y708C 375:379 Y708C 375:379 Y708C 375:379 Four such mutants (L658F, Y708C, R776W, and G959A) bound (125)I-C-type natriuretic peptide on the surface of cells but failed to synthesize cGMP in membrane GC assays. 26980729 1 52 theme C-type 151:156 arg1 peptide 170:176 C-type natriuretic peptide 151:176 C-type natriuretic peptide activation 151:187 C-type natriuretic peptide activation of guanylyl cyclase B (GC-B), also known as natriuretic peptide receptor B or NPR2, stimulates long bone growth, and missense mutations in GC-B cause dwarfism. 26980729 5 53 theme PNGase 1067:1072 arg1 deglycosylation 1076:1090 PNGase F deglycosylation 1067:1090 PNGase F deglycosylation of fully processed GC-B 1067:1114 Tunicamycin inhibition of glycosylation in the endoplasmic reticulum or mutation of the Asn-24 glycosylation site decreased GC activity, but neither inhibition of glycosylation in the Golgi by N-acetylglucosaminyltransferase I gene inactivation nor PNGase F deglycosylation of fully processed GC-B reduced GC activity. 26980729 1 54 theme natriuretic 158:168 arg1 peptide 170:176 C-type natriuretic peptide 151:176 C-type natriuretic peptide activation 151:187 C-type natriuretic peptide activation of guanylyl cyclase B (GC-B), also known as natriuretic peptide receptor B or NPR2, stimulates long bone growth, and missense mutations in GC-B cause dwarfism. 26980729 5 55 theme glycosylation 844:856 arg1 inhibition 830:839 Tunicamycin inhibition 818:839 Tunicamycin inhibition of glycosylation in the endoplasmic reticulum or mutation of the Asn-24 glycosylation site 818:930 Tunicamycin inhibition of glycosylation in the endoplasmic reticulum or mutation of the Asn-24 glycosylation site decreased GC activity, but neither inhibition of glycosylation in the Golgi by N-acetylglucosaminyltransferase I gene inactivation nor PNGase F deglycosylation of fully processed GC-B reduced GC activity. 26980729 1 56 theme natriuretic 233:243 arg1 receptor 253:260 natriuretic peptide receptor 233:260 natriuretic peptide receptor B 233:262 C-type natriuretic peptide activation of guanylyl cyclase B (GC-B), also known as natriuretic peptide receptor B or NPR2, stimulates long bone growth, and missense mutations in GC-B cause dwarfism. 26980729 1 57 from mutations 315:323 arg1 GC-B 328:331 GC-B 328:331 GC-B 328:331 C-type natriuretic peptide activation of guanylyl cyclase B (GC-B), also known as natriuretic peptide receptor B or NPR2, stimulates long bone growth, and missense mutations in GC-B cause dwarfism. 26980729 6 58 theme catalytic 1242:1250 arg1 formation 1219:1227 the formation 1215:1227 the formation of an active catalytic, but not ligand-binding domain 1215:1281 We conclude that endoplasmic reticulum-mediated glycosylation is required for the formation of an active catalytic, but not ligand-binding domain, and that mutations that inhibit this process cause dwarfism. 26980729 1 59 theme peptide 170:176 arg1 activation 178:187 C-type natriuretic peptide activation 151:187 C-type natriuretic peptide activation 151:187 C-type natriuretic peptide activation of guanylyl cyclase B (GC-B), also known as natriuretic peptide receptor B or NPR2, stimulates long bone growth, and missense mutations in GC-B cause dwarfism. 26980729 1 60 theme peptide 245:251 arg1 receptor 253:260 natriuretic peptide receptor 233:260 natriuretic peptide receptor B 233:262 C-type natriuretic peptide activation of guanylyl cyclase B (GC-B), also known as natriuretic peptide receptor B or NPR2, stimulates long bone growth, and missense mutations in GC-B cause dwarfism. 29161034 9 0 theme trafficking 1818:1828 arg1 pathway 1830:1836 the vertebrate COPII-dependent trafficking pathway 1787:1836 the vertebrate COPII-dependent trafficking pathway 1787:1836 Our results indicate that O-GlcNAc is a conserved and critical regulatory modification in the vertebrate COPII-dependent trafficking pathway. 29161034 8 1 theme human 1522:1526 arg1 cells 1528:1532 human cells 1522:1532 human cells 1522:1532 In particular, we show that individual O-GlcNAcylation sites of SEC23A, an essential COPII component, are required for its function in human cells and vertebrate development, because mutation of these sites impairs SEC23A-dependent in vivo collagen trafficking and skeletogenesis in a zebrafish model of CLSD. 29161034 1 2 theme endoplasmic 156:166 arg1 reticulum 168:176 the endoplasmic reticulum 152:176 the endoplasmic reticulum 152:176 The COPII coat complex, which mediates secretory cargo trafficking from the endoplasmic reticulum, is a key control point for subcellular protein targeting. 29161034 9 3 theme regulatory 1760:1769 arg1 modification 1771:1782 a conserved and critical regulatory modification 1735:1782 a conserved and critical regulatory modification in the vertebrate COPII-dependent trafficking pathway 1735:1836 Our results indicate that O-GlcNAc is a conserved and critical regulatory modification in the vertebrate COPII-dependent trafficking pathway. 29161034 9 3 theme regulatory 1760:1769 arg1 O-GlcNAc 1723:1730 O-GlcNAc 1723:1730 O-GlcNAc 1723:1730 Our results indicate that O-GlcNAc is a conserved and critical regulatory modification in the vertebrate COPII-dependent trafficking pathway. 29161034 8 4 theme zebrafish 1672:1680 arg1 model 1682:1686 a zebrafish model 1670:1686 a zebrafish model of CLSD 1670:1694 In particular, we show that individual O-GlcNAcylation sites of SEC23A, an essential COPII component, are required for its function in human cells and vertebrate development, because mutation of these sites impairs SEC23A-dependent in vivo collagen trafficking and skeletogenesis in a zebrafish model of CLSD. 29161034 8 5 theme vertebrate 1538:1547 arg1 development 1549:1559 vertebrate development 1538:1559 vertebrate development 1538:1559 In particular, we show that individual O-GlcNAcylation sites of SEC23A, an essential COPII component, are required for its function in human cells and vertebrate development, because mutation of these sites impairs SEC23A-dependent in vivo collagen trafficking and skeletogenesis in a zebrafish model of CLSD. 29161034 5 6 theme metabolic 906:914 arg1 cues 933:936 developmental, metabolic, or pathological cues 891:936 developmental, metabolic, or pathological cues 891:936 However, little is known about how vertebrates dynamically regulate COPII activity in response to developmental, metabolic, or pathological cues. 29161034 4 7 theme cell 708:711 arg1 physiology 713:722 normal cell physiology 701:722 normal cell physiology 701:722 Detailed knowledge of the COPII pathway is required to understand its role in normal cell physiology and to devise new treatments for disorders in which it is disrupted. 29161034 7 8 theme cargo 1370:1374 arg1 secretion 1376:1384 cargo secretion 1370:1384 cargo secretion 1370:1384 Here, we use a combination of chemical, biochemical, cellular, and genetic approaches to demonstrate that site-specific O-GlcNAcylation of COPII proteins mediates their protein-protein interactions and modulates cargo secretion. 29161034 1 9 from reticulum 168:176 arg1 trafficking 135:145 secretory cargo trafficking 119:145 secretory cargo trafficking from the endoplasmic reticulum 119:176 The COPII coat complex, which mediates secretory cargo trafficking from the endoplasmic reticulum, is a key control point for subcellular protein targeting. 29161034 3 10 theme trafficking 546:556 arg1 defects 558:564 collagen trafficking defects 537:564 collagen trafficking defects 537:564 Indeed, mutations in COPII genes cause a range of human pathologies, including cranio-lenticulo-sutural dysplasia (CLSD), which is characterized by collagen trafficking defects, craniofacial abnormalities, and skeletal dysmorphology. 29161034 8 11 theme essential 1462:1470 arg1 component 1478:1486 an essential COPII component 1459:1486 an essential COPII component 1459:1486 In particular, we show that individual O-GlcNAcylation sites of SEC23A, an essential COPII component, are required for its function in human cells and vertebrate development, because mutation of these sites impairs SEC23A-dependent in vivo collagen trafficking and skeletogenesis in a zebrafish model of CLSD. 29161034 8 11 theme essential 1462:1470 arg1 SEC23A 1451:1456 SEC23A 1451:1456 SEC23A 1451:1456 In particular, we show that individual O-GlcNAcylation sites of SEC23A, an essential COPII component, are required for its function in human cells and vertebrate development, because mutation of these sites impairs SEC23A-dependent in vivo collagen trafficking and skeletogenesis in a zebrafish model of CLSD. 29161034 7 12 theme biochemical 1198:1208 arg1 approaches 1233:1242 chemical, biochemical, cellular, and genetic approaches 1188:1242 chemical, biochemical, cellular, and genetic approaches 1188:1242 Here, we use a combination of chemical, biochemical, cellular, and genetic approaches to demonstrate that site-specific O-GlcNAcylation of COPII proteins mediates their protein-protein interactions and modulates cargo secretion. 29161034 4 13 theme new 738:740 arg1 treatments 742:751 new treatments 738:751 new treatments for disorders in which it is disrupted 738:790 Detailed knowledge of the COPII pathway is required to understand its role in normal cell physiology and to devise new treatments for disorders in which it is disrupted. 29161034 4 14 from role 693:696 arg1 physiology 713:722 normal cell physiology 701:722 normal cell physiology 701:722 Detailed knowledge of the COPII pathway is required to understand its role in normal cell physiology and to devise new treatments for disorders in which it is disrupted. 29161034 7 15 theme protein-protein 1327:1341 arg1 interactions 1343:1354 their protein-protein interactions 1321:1354 their protein-protein interactions 1321:1354 Here, we use a combination of chemical, biochemical, cellular, and genetic approaches to demonstrate that site-specific O-GlcNAcylation of COPII proteins mediates their protein-protein interactions and modulates cargo secretion. 29161034 7 16 theme COPII 1297:1301 arg1 proteins 1303:1310 COPII proteins 1297:1310 COPII proteins 1297:1310 Here, we use a combination of chemical, biochemical, cellular, and genetic approaches to demonstrate that site-specific O-GlcNAcylation of COPII proteins mediates their protein-protein interactions and modulates cargo secretion. 29161034 4 17 theme COPII 649:653 arg1 pathway 655:661 the COPII pathway 645:661 the COPII pathway 645:661 Detailed knowledge of the COPII pathway is required to understand its role in normal cell physiology and to devise new treatments for disorders in which it is disrupted. 29161034 2 18 theme protein 283:289 arg1 sorting 291:297 protein sorting 283:297 protein sorting by COPII 283:306 Because misdirected proteins cannot function, protein sorting by COPII is critical for establishing and maintaining normal cell and tissue homeostasis. 29161034 6 19 theme glycosylation 1061:1073 arg1 form 1031:1034 a dynamic form 1021:1034 a dynamic form of intracellular protein glycosylation 1021:1073 Several COPII proteins are modified by O-linked β-N-acetylglucosamine (O-GlcNAc), a dynamic form of intracellular protein glycosylation, but the biochemical and functional effects of these modifications remain unclear. 29161034 6 19 theme glycosylation 1061:1073 arg1 β-N-acetylglucosamine 987:1007 O-linked β-N-acetylglucosamine 978:1007 O-linked β-N-acetylglucosamine (O-GlcNAc) 978:1018 Several COPII proteins are modified by O-linked β-N-acetylglucosamine (O-GlcNAc), a dynamic form of intracellular protein glycosylation, but the biochemical and functional effects of these modifications remain unclear. 29161034 0 20 theme Protein 51:57 arg1 Pathway 71:77 the Vertebrate COPII Protein Trafficking Pathway 30:77 the Vertebrate COPII Protein Trafficking Pathway 30:77 Dynamic Glycosylation Governs the Vertebrate COPII Protein Trafficking Pathway. 29161034 1 21 theme COPII 84:88 arg1 complex 95:101 The COPII coat complex 80:101 The COPII coat complex 80:101 The COPII coat complex, which mediates secretory cargo trafficking from the endoplasmic reticulum, is a key control point for subcellular protein targeting. 29161034 1 21 theme COPII 84:88 arg1 point 196:200 a key control point 182:200 a key control point for subcellular protein targeting 182:234 The COPII coat complex, which mediates secretory cargo trafficking from the endoplasmic reticulum, is a key control point for subcellular protein targeting. 29161034 6 22 theme functional 1100:1109 arg1 effects 1111:1117 the biochemical and functional effects 1080:1117 the biochemical and functional effects of these modifications 1080:1140 Several COPII proteins are modified by O-linked β-N-acetylglucosamine (O-GlcNAc), a dynamic form of intracellular protein glycosylation, but the biochemical and functional effects of these modifications remain unclear. 29161034 3 23 theme human 439:443 arg1 dysplasia 493:501 cranio-lenticulo-sutural dysplasia 468:501 cranio-lenticulo-sutural dysplasia (CLSD) 468:508 Indeed, mutations in COPII genes cause a range of human pathologies, including cranio-lenticulo-sutural dysplasia (CLSD), which is characterized by collagen trafficking defects, craniofacial abnormalities, and skeletal dysmorphology. 29161034 3 23 theme human 439:443 arg1 pathologies 445:455 human pathologies 439:455 human pathologies 439:455 Indeed, mutations in COPII genes cause a range of human pathologies, including cranio-lenticulo-sutural dysplasia (CLSD), which is characterized by collagen trafficking defects, craniofacial abnormalities, and skeletal dysmorphology. 29161034 3 24 from mutations 397:405 arg1 genes 416:420 COPII genes 410:420 COPII genes 410:420 Indeed, mutations in COPII genes cause a range of human pathologies, including cranio-lenticulo-sutural dysplasia (CLSD), which is characterized by collagen trafficking defects, craniofacial abnormalities, and skeletal dysmorphology. 29161034 8 25 theme collagen 1627:1634 arg1 trafficking 1636:1646 SEC23A-dependent in vivo collagen trafficking 1602:1646 SEC23A-dependent in vivo collagen trafficking 1602:1646 In particular, we show that individual O-GlcNAcylation sites of SEC23A, an essential COPII component, are required for its function in human cells and vertebrate development, because mutation of these sites impairs SEC23A-dependent in vivo collagen trafficking and skeletogenesis in a zebrafish model of CLSD. 29161034 7 26 theme genetic 1225:1231 arg1 approaches 1233:1242 chemical, biochemical, cellular, and genetic approaches 1188:1242 chemical, biochemical, cellular, and genetic approaches 1188:1242 Here, we use a combination of chemical, biochemical, cellular, and genetic approaches to demonstrate that site-specific O-GlcNAcylation of COPII proteins mediates their protein-protein interactions and modulates cargo secretion. 29161034 1 27 theme coat 90:93 arg1 complex 95:101 The COPII coat complex 80:101 The COPII coat complex 80:101 The COPII coat complex, which mediates secretory cargo trafficking from the endoplasmic reticulum, is a key control point for subcellular protein targeting. 29161034 1 27 theme coat 90:93 arg1 point 196:200 a key control point 182:200 a key control point for subcellular protein targeting 182:234 The COPII coat complex, which mediates secretory cargo trafficking from the endoplasmic reticulum, is a key control point for subcellular protein targeting. 29161034 0 28 theme Dynamic 0:6 arg1 Glycosylation 8:20 Dynamic Glycosylation 0:20 Dynamic Glycosylation 0:20 Dynamic Glycosylation Governs the Vertebrate COPII Protein Trafficking Pathway. 29161034 9 29 theme critical 1751:1758 arg1 modification 1771:1782 a conserved and critical regulatory modification 1735:1782 a conserved and critical regulatory modification in the vertebrate COPII-dependent trafficking pathway 1735:1836 Our results indicate that O-GlcNAc is a conserved and critical regulatory modification in the vertebrate COPII-dependent trafficking pathway. 29161034 9 29 theme critical 1751:1758 arg1 O-GlcNAc 1723:1730 O-GlcNAc 1723:1730 O-GlcNAc 1723:1730 Our results indicate that O-GlcNAc is a conserved and critical regulatory modification in the vertebrate COPII-dependent trafficking pathway. 29161034 9 30 theme vertebrate 1791:1800 arg1 pathway 1830:1836 the vertebrate COPII-dependent trafficking pathway 1787:1836 the vertebrate COPII-dependent trafficking pathway 1787:1836 Our results indicate that O-GlcNAc is a conserved and critical regulatory modification in the vertebrate COPII-dependent trafficking pathway. 29161034 1 31 theme key 184:186 arg1 point 196:200 a key control point 182:200 a key control point for subcellular protein targeting 182:234 The COPII coat complex, which mediates secretory cargo trafficking from the endoplasmic reticulum, is a key control point for subcellular protein targeting. 29161034 1 31 theme key 184:186 arg1 complex 95:101 The COPII coat complex 80:101 The COPII coat complex 80:101 The COPII coat complex, which mediates secretory cargo trafficking from the endoplasmic reticulum, is a key control point for subcellular protein targeting. 29161034 6 32 theme O-linked 978:985 arg1 form 1031:1034 a dynamic form 1021:1034 a dynamic form of intracellular protein glycosylation 1021:1073 Several COPII proteins are modified by O-linked β-N-acetylglucosamine (O-GlcNAc), a dynamic form of intracellular protein glycosylation, but the biochemical and functional effects of these modifications remain unclear. 29161034 6 32 theme O-linked 978:985 arg1 O-GlcNAc 1010:1017 O-GlcNAc 1010:1017 O-GlcNAc 1010:1017 Several COPII proteins are modified by O-linked β-N-acetylglucosamine (O-GlcNAc), a dynamic form of intracellular protein glycosylation, but the biochemical and functional effects of these modifications remain unclear. 29161034 6 32 theme O-linked 978:985 arg1 β-N-acetylglucosamine 987:1007 O-linked β-N-acetylglucosamine 978:1007 O-linked β-N-acetylglucosamine (O-GlcNAc) 978:1018 Several COPII proteins are modified by O-linked β-N-acetylglucosamine (O-GlcNAc), a dynamic form of intracellular protein glycosylation, but the biochemical and functional effects of these modifications remain unclear. 29161034 6 33 link O-linked 978:985 arg1 form 1031:1034 a dynamic form 1021:1034 a dynamic form of intracellular protein glycosylation 1021:1073 Several COPII proteins are modified by O-linked β-N-acetylglucosamine (O-GlcNAc), a dynamic form of intracellular protein glycosylation, but the biochemical and functional effects of these modifications remain unclear. 29161034 6 33 link O-linked 978:985 arg1 O-GlcNAc 1010:1017 O-GlcNAc 1010:1017 O-GlcNAc 1010:1017 Several COPII proteins are modified by O-linked β-N-acetylglucosamine (O-GlcNAc), a dynamic form of intracellular protein glycosylation, but the biochemical and functional effects of these modifications remain unclear. 29161034 6 33 link O-linked 978:985 arg1 β-N-acetylglucosamine 987:1007 O-linked β-N-acetylglucosamine 978:1007 O-linked β-N-acetylglucosamine (O-GlcNAc) 978:1018 Several COPII proteins are modified by O-linked β-N-acetylglucosamine (O-GlcNAc), a dynamic form of intracellular protein glycosylation, but the biochemical and functional effects of these modifications remain unclear. 29161034 8 34 theme individual 1415:1424 arg1 SEC23A 1451:1456 SEC23A 1451:1456 SEC23A 1451:1456 In particular, we show that individual O-GlcNAcylation sites of SEC23A, an essential COPII component, are required for its function in human cells and vertebrate development, because mutation of these sites impairs SEC23A-dependent in vivo collagen trafficking and skeletogenesis in a zebrafish model of CLSD. 29161034 8 34 theme individual 1415:1424 arg1 sites 1442:1446 individual O-GlcNAcylation sites 1415:1446 individual O-GlcNAcylation sites of SEC23A, an essential COPII component, 1415:1487 In particular, we show that individual O-GlcNAcylation sites of SEC23A, an essential COPII component, are required for its function in human cells and vertebrate development, because mutation of these sites impairs SEC23A-dependent in vivo collagen trafficking and skeletogenesis in a zebrafish model of CLSD. 29161034 1 35 theme control 188:194 arg1 point 196:200 a key control point 182:200 a key control point for subcellular protein targeting 182:234 The COPII coat complex, which mediates secretory cargo trafficking from the endoplasmic reticulum, is a key control point for subcellular protein targeting. 29161034 1 35 theme control 188:194 arg1 complex 95:101 The COPII coat complex 80:101 The COPII coat complex 80:101 The COPII coat complex, which mediates secretory cargo trafficking from the endoplasmic reticulum, is a key control point for subcellular protein targeting. 29161034 9 36 theme conserved 1737:1745 arg1 modification 1771:1782 a conserved and critical regulatory modification 1735:1782 a conserved and critical regulatory modification in the vertebrate COPII-dependent trafficking pathway 1735:1836 Our results indicate that O-GlcNAc is a conserved and critical regulatory modification in the vertebrate COPII-dependent trafficking pathway. 29161034 9 36 theme conserved 1737:1745 arg1 O-GlcNAc 1723:1730 O-GlcNAc 1723:1730 O-GlcNAc 1723:1730 Our results indicate that O-GlcNAc is a conserved and critical regulatory modification in the vertebrate COPII-dependent trafficking pathway. 29161034 3 37 theme craniofacial 567:578 arg1 abnormalities 580:592 craniofacial abnormalities 567:592 craniofacial abnormalities 567:592 Indeed, mutations in COPII genes cause a range of human pathologies, including cranio-lenticulo-sutural dysplasia (CLSD), which is characterized by collagen trafficking defects, craniofacial abnormalities, and skeletal dysmorphology. 29161034 3 38 theme cranio-lenticulo-sutural 468:491 arg1 CLSD 504:507 CLSD 504:507 CLSD 504:507 Indeed, mutations in COPII genes cause a range of human pathologies, including cranio-lenticulo-sutural dysplasia (CLSD), which is characterized by collagen trafficking defects, craniofacial abnormalities, and skeletal dysmorphology. 29161034 3 38 theme cranio-lenticulo-sutural 468:491 arg1 dysplasia 493:501 cranio-lenticulo-sutural dysplasia 468:501 cranio-lenticulo-sutural dysplasia (CLSD) 468:508 Indeed, mutations in COPII genes cause a range of human pathologies, including cranio-lenticulo-sutural dysplasia (CLSD), which is characterized by collagen trafficking defects, craniofacial abnormalities, and skeletal dysmorphology. 29161034 0 39 theme COPII 45:49 arg1 Pathway 71:77 the Vertebrate COPII Protein Trafficking Pathway 30:77 the Vertebrate COPII Protein Trafficking Pathway 30:77 Dynamic Glycosylation Governs the Vertebrate COPII Protein Trafficking Pathway. 29161034 5 40 theme pathological 920:931 arg1 cues 933:936 developmental, metabolic, or pathological cues 891:936 developmental, metabolic, or pathological cues 891:936 However, little is known about how vertebrates dynamically regulate COPII activity in response to developmental, metabolic, or pathological cues. 29161034 6 41 theme protein 1053:1059 arg1 glycosylation 1061:1073 intracellular protein glycosylation 1039:1073 intracellular protein glycosylation 1039:1073 Several COPII proteins are modified by O-linked β-N-acetylglucosamine (O-GlcNAc), a dynamic form of intracellular protein glycosylation, but the biochemical and functional effects of these modifications remain unclear. 29161034 3 42 theme pathologies 445:455 arg1 dysplasia 493:501 cranio-lenticulo-sutural dysplasia 468:501 cranio-lenticulo-sutural dysplasia (CLSD) 468:508 Indeed, mutations in COPII genes cause a range of human pathologies, including cranio-lenticulo-sutural dysplasia (CLSD), which is characterized by collagen trafficking defects, craniofacial abnormalities, and skeletal dysmorphology. 29161034 3 42 theme pathologies 445:455 arg1 range 430:434 a range 428:434 a range 428:434 Indeed, mutations in COPII genes cause a range of human pathologies, including cranio-lenticulo-sutural dysplasia (CLSD), which is characterized by collagen trafficking defects, craniofacial abnormalities, and skeletal dysmorphology. 29161034 0 43 theme Vertebrate 34:43 arg1 Pathway 71:77 the Vertebrate COPII Protein Trafficking Pathway 30:77 the Vertebrate COPII Protein Trafficking Pathway 30:77 Dynamic Glycosylation Governs the Vertebrate COPII Protein Trafficking Pathway. 29161034 8 44 theme in 1619:1620 arg1 trafficking 1636:1646 SEC23A-dependent in vivo collagen trafficking 1602:1646 SEC23A-dependent in vivo collagen trafficking 1602:1646 In particular, we show that individual O-GlcNAcylation sites of SEC23A, an essential COPII component, are required for its function in human cells and vertebrate development, because mutation of these sites impairs SEC23A-dependent in vivo collagen trafficking and skeletogenesis in a zebrafish model of CLSD. 29161034 8 45 theme SEC23A-dependent 1602:1617 arg1 trafficking 1636:1646 SEC23A-dependent in vivo collagen trafficking 1602:1646 SEC23A-dependent in vivo collagen trafficking 1602:1646 In particular, we show that individual O-GlcNAcylation sites of SEC23A, an essential COPII component, are required for its function in human cells and vertebrate development, because mutation of these sites impairs SEC23A-dependent in vivo collagen trafficking and skeletogenesis in a zebrafish model of CLSD. 29161034 8 46 dep in 1619:1620 arg1 vivo 1622:1625 vivo 1622:1625 vivo 1622:1625 In particular, we show that individual O-GlcNAcylation sites of SEC23A, an essential COPII component, are required for its function in human cells and vertebrate development, because mutation of these sites impairs SEC23A-dependent in vivo collagen trafficking and skeletogenesis in a zebrafish model of CLSD. 29161034 8 47 theme O-GlcNAcylation 1426:1440 arg1 SEC23A 1451:1456 SEC23A 1451:1456 SEC23A 1451:1456 In particular, we show that individual O-GlcNAcylation sites of SEC23A, an essential COPII component, are required for its function in human cells and vertebrate development, because mutation of these sites impairs SEC23A-dependent in vivo collagen trafficking and skeletogenesis in a zebrafish model of CLSD. 29161034 8 47 theme O-GlcNAcylation 1426:1440 arg1 sites 1442:1446 individual O-GlcNAcylation sites 1415:1446 individual O-GlcNAcylation sites of SEC23A, an essential COPII component, 1415:1487 In particular, we show that individual O-GlcNAcylation sites of SEC23A, an essential COPII component, are required for its function in human cells and vertebrate development, because mutation of these sites impairs SEC23A-dependent in vivo collagen trafficking and skeletogenesis in a zebrafish model of CLSD. 29161034 1 48 theme subcellular 206:216 arg1 targeting 226:234 subcellular protein targeting 206:234 subcellular protein targeting 206:234 The COPII coat complex, which mediates secretory cargo trafficking from the endoplasmic reticulum, is a key control point for subcellular protein targeting. 29161034 0 49 theme Trafficking 59:69 arg1 Pathway 71:77 the Vertebrate COPII Protein Trafficking Pathway 30:77 the Vertebrate COPII Protein Trafficking Pathway 30:77 Dynamic Glycosylation Governs the Vertebrate COPII Protein Trafficking Pathway. 29161034 5 50 theme developmental 891:903 arg1 cues 933:936 developmental, metabolic, or pathological cues 891:936 developmental, metabolic, or pathological cues 891:936 However, little is known about how vertebrates dynamically regulate COPII activity in response to developmental, metabolic, or pathological cues. 29161034 6 51 theme intracellular 1039:1051 arg1 glycosylation 1061:1073 intracellular protein glycosylation 1039:1073 intracellular protein glycosylation 1039:1073 Several COPII proteins are modified by O-linked β-N-acetylglucosamine (O-GlcNAc), a dynamic form of intracellular protein glycosylation, but the biochemical and functional effects of these modifications remain unclear. 29161034 9 52 theme COPII-dependent 1802:1816 arg1 pathway 1830:1836 the vertebrate COPII-dependent trafficking pathway 1787:1836 the vertebrate COPII-dependent trafficking pathway 1787:1836 Our results indicate that O-GlcNAc is a conserved and critical regulatory modification in the vertebrate COPII-dependent trafficking pathway. 29161034 8 53 theme SEC23A 1451:1456 arg1 SEC23A 1451:1456 SEC23A 1451:1456 SEC23A 1451:1456 In particular, we show that individual O-GlcNAcylation sites of SEC23A, an essential COPII component, are required for its function in human cells and vertebrate development, because mutation of these sites impairs SEC23A-dependent in vivo collagen trafficking and skeletogenesis in a zebrafish model of CLSD. 29161034 8 53 theme SEC23A 1451:1456 arg1 sites 1442:1446 individual O-GlcNAcylation sites 1415:1446 individual O-GlcNAcylation sites of SEC23A, an essential COPII component, 1415:1487 In particular, we show that individual O-GlcNAcylation sites of SEC23A, an essential COPII component, are required for its function in human cells and vertebrate development, because mutation of these sites impairs SEC23A-dependent in vivo collagen trafficking and skeletogenesis in a zebrafish model of CLSD. 29161034 2 54 theme normal 353:358 arg1 cell 360:363 normal cell and tissue homeostasis 353:386 cell 360:363 Because misdirected proteins cannot function, protein sorting by COPII is critical for establishing and maintaining normal cell and tissue homeostasis. 29161034 3 55 theme COPII 410:414 arg1 genes 416:420 COPII genes 410:420 COPII genes 410:420 Indeed, mutations in COPII genes cause a range of human pathologies, including cranio-lenticulo-sutural dysplasia (CLSD), which is characterized by collagen trafficking defects, craniofacial abnormalities, and skeletal dysmorphology. 29161034 6 56 theme COPII 947:951 arg1 proteins 953:960 Several COPII proteins 939:960 Several COPII proteins 939:960 Several COPII proteins are modified by O-linked β-N-acetylglucosamine (O-GlcNAc), a dynamic form of intracellular protein glycosylation, but the biochemical and functional effects of these modifications remain unclear. 29161034 8 57 theme sites 1588:1592 arg1 mutation 1570:1577 mutation 1570:1577 mutation of these sites 1570:1592 In particular, we show that individual O-GlcNAcylation sites of SEC23A, an essential COPII component, are required for its function in human cells and vertebrate development, because mutation of these sites impairs SEC23A-dependent in vivo collagen trafficking and skeletogenesis in a zebrafish model of CLSD. 29161034 3 58 theme skeletal 599:606 arg1 dysmorphology 608:620 skeletal dysmorphology 599:620 skeletal dysmorphology 599:620 Indeed, mutations in COPII genes cause a range of human pathologies, including cranio-lenticulo-sutural dysplasia (CLSD), which is characterized by collagen trafficking defects, craniofacial abnormalities, and skeletal dysmorphology. 29161034 1 59 theme secretory 119:127 arg1 trafficking 135:145 secretory cargo trafficking 119:145 secretory cargo trafficking from the endoplasmic reticulum 119:176 The COPII coat complex, which mediates secretory cargo trafficking from the endoplasmic reticulum, is a key control point for subcellular protein targeting. 29161034 6 60 theme Several 939:945 arg1 proteins 953:960 Several COPII proteins 939:960 Several COPII proteins 939:960 Several COPII proteins are modified by O-linked β-N-acetylglucosamine (O-GlcNAc), a dynamic form of intracellular protein glycosylation, but the biochemical and functional effects of these modifications remain unclear. 29161034 7 61 theme site-specific 1264:1276 arg1 O-GlcNAcylation 1278:1292 site-specific O-GlcNAcylation 1264:1292 site-specific O-GlcNAcylation of COPII proteins 1264:1310 Here, we use a combination of chemical, biochemical, cellular, and genetic approaches to demonstrate that site-specific O-GlcNAcylation of COPII proteins mediates their protein-protein interactions and modulates cargo secretion. 29161034 1 62 theme cargo 129:133 arg1 trafficking 135:145 secretory cargo trafficking 119:145 secretory cargo trafficking from the endoplasmic reticulum 119:176 The COPII coat complex, which mediates secretory cargo trafficking from the endoplasmic reticulum, is a key control point for subcellular protein targeting. 29161034 8 63 theme CLSD 1691:1694 arg1 model 1682:1686 a zebrafish model 1670:1686 a zebrafish model of CLSD 1670:1694 In particular, we show that individual O-GlcNAcylation sites of SEC23A, an essential COPII component, are required for its function in human cells and vertebrate development, because mutation of these sites impairs SEC23A-dependent in vivo collagen trafficking and skeletogenesis in a zebrafish model of CLSD. 29161034 1 64 theme protein 218:224 arg1 targeting 226:234 subcellular protein targeting 206:234 subcellular protein targeting 206:234 The COPII coat complex, which mediates secretory cargo trafficking from the endoplasmic reticulum, is a key control point for subcellular protein targeting. 29161034 3 65 theme collagen 537:544 arg1 defects 558:564 collagen trafficking defects 537:564 collagen trafficking defects 537:564 Indeed, mutations in COPII genes cause a range of human pathologies, including cranio-lenticulo-sutural dysplasia (CLSD), which is characterized by collagen trafficking defects, craniofacial abnormalities, and skeletal dysmorphology. 29161034 7 66 theme proteins 1303:1310 arg1 O-GlcNAcylation 1278:1292 site-specific O-GlcNAcylation 1264:1292 site-specific O-GlcNAcylation of COPII proteins 1264:1310 Here, we use a combination of chemical, biochemical, cellular, and genetic approaches to demonstrate that site-specific O-GlcNAcylation of COPII proteins mediates their protein-protein interactions and modulates cargo secretion. 29161034 6 67 theme modifications 1128:1140 arg1 effects 1111:1117 the biochemical and functional effects 1080:1117 the biochemical and functional effects of these modifications 1080:1140 Several COPII proteins are modified by O-linked β-N-acetylglucosamine (O-GlcNAc), a dynamic form of intracellular protein glycosylation, but the biochemical and functional effects of these modifications remain unclear. 29161034 8 68 from function 1510:1517 arg1 cells 1528:1532 human cells 1522:1532 human cells 1522:1532 In particular, we show that individual O-GlcNAcylation sites of SEC23A, an essential COPII component, are required for its function in human cells and vertebrate development, because mutation of these sites impairs SEC23A-dependent in vivo collagen trafficking and skeletogenesis in a zebrafish model of CLSD. 29161034 8 68 from function 1510:1517 arg1 development 1549:1559 vertebrate development 1538:1559 vertebrate development 1538:1559 In particular, we show that individual O-GlcNAcylation sites of SEC23A, an essential COPII component, are required for its function in human cells and vertebrate development, because mutation of these sites impairs SEC23A-dependent in vivo collagen trafficking and skeletogenesis in a zebrafish model of CLSD. 29161034 4 69 theme Detailed 623:630 arg1 knowledge 632:640 Detailed knowledge 623:640 Detailed knowledge of the COPII pathway 623:661 Detailed knowledge of the COPII pathway is required to understand its role in normal cell physiology and to devise new treatments for disorders in which it is disrupted. 29161034 6 70 mod modified 966:973 arg1 proteins 953:960 Several COPII proteins 939:960 Several COPII proteins 939:960 Several COPII proteins are modified by O-linked β-N-acetylglucosamine (O-GlcNAc), a dynamic form of intracellular protein glycosylation, but the biochemical and functional effects of these modifications remain unclear. 29161034 6 70 mod modified 966:973 arg3 β-N-acetylglucosamine 987:1007 O-linked β-N-acetylglucosamine 978:1007 O-linked β-N-acetylglucosamine (O-GlcNAc) 978:1018 Several COPII proteins are modified by O-linked β-N-acetylglucosamine (O-GlcNAc), a dynamic form of intracellular protein glycosylation, but the biochemical and functional effects of these modifications remain unclear. 29161034 6 70 mod modified 966:973 arg3 O-GlcNAc 1010:1017 O-GlcNAc 1010:1017 O-GlcNAc 1010:1017 Several COPII proteins are modified by O-linked β-N-acetylglucosamine (O-GlcNAc), a dynamic form of intracellular protein glycosylation, but the biochemical and functional effects of these modifications remain unclear. 29161034 6 70 mod modified 966:973 arg3 form 1031:1034 a dynamic form 1021:1034 a dynamic form of intracellular protein glycosylation 1021:1073 Several COPII proteins are modified by O-linked β-N-acetylglucosamine (O-GlcNAc), a dynamic form of intracellular protein glycosylation, but the biochemical and functional effects of these modifications remain unclear. 29161034 5 71 theme COPII 861:865 arg1 activity 867:874 COPII activity 861:874 COPII activity 861:874 However, little is known about how vertebrates dynamically regulate COPII activity in response to developmental, metabolic, or pathological cues. 29161034 8 72 theme COPII 1472:1476 arg1 component 1478:1486 an essential COPII component 1459:1486 an essential COPII component 1459:1486 In particular, we show that individual O-GlcNAcylation sites of SEC23A, an essential COPII component, are required for its function in human cells and vertebrate development, because mutation of these sites impairs SEC23A-dependent in vivo collagen trafficking and skeletogenesis in a zebrafish model of CLSD. 29161034 8 72 theme COPII 1472:1476 arg1 SEC23A 1451:1456 SEC23A 1451:1456 SEC23A 1451:1456 In particular, we show that individual O-GlcNAcylation sites of SEC23A, an essential COPII component, are required for its function in human cells and vertebrate development, because mutation of these sites impairs SEC23A-dependent in vivo collagen trafficking and skeletogenesis in a zebrafish model of CLSD. 29161034 4 73 theme pathway 655:661 arg1 knowledge 632:640 Detailed knowledge 623:640 Detailed knowledge of the COPII pathway 623:661 Detailed knowledge of the COPII pathway is required to understand its role in normal cell physiology and to devise new treatments for disorders in which it is disrupted. 29161034 4 74 theme normal 701:706 arg1 physiology 713:722 normal cell physiology 701:722 normal cell physiology 701:722 Detailed knowledge of the COPII pathway is required to understand its role in normal cell physiology and to devise new treatments for disorders in which it is disrupted. 29161034 6 75 theme biochemical 1084:1094 arg1 effects 1111:1117 the biochemical and functional effects 1080:1117 the biochemical and functional effects of these modifications 1080:1140 Several COPII proteins are modified by O-linked β-N-acetylglucosamine (O-GlcNAc), a dynamic form of intracellular protein glycosylation, but the biochemical and functional effects of these modifications remain unclear. 29161034 6 76 theme dynamic 1023:1029 arg1 form 1031:1034 a dynamic form 1021:1034 a dynamic form of intracellular protein glycosylation 1021:1073 Several COPII proteins are modified by O-linked β-N-acetylglucosamine (O-GlcNAc), a dynamic form of intracellular protein glycosylation, but the biochemical and functional effects of these modifications remain unclear. 29161034 6 76 theme dynamic 1023:1029 arg1 β-N-acetylglucosamine 987:1007 O-linked β-N-acetylglucosamine 978:1007 O-linked β-N-acetylglucosamine (O-GlcNAc) 978:1018 Several COPII proteins are modified by O-linked β-N-acetylglucosamine (O-GlcNAc), a dynamic form of intracellular protein glycosylation, but the biochemical and functional effects of these modifications remain unclear. 29161034 7 77 theme approaches 1233:1242 arg1 combination 1173:1183 a combination 1171:1183 a combination of chemical, biochemical, cellular, and genetic approaches 1171:1242 Here, we use a combination of chemical, biochemical, cellular, and genetic approaches to demonstrate that site-specific O-GlcNAcylation of COPII proteins mediates their protein-protein interactions and modulates cargo secretion. 29161034 2 78 theme misdirected 245:255 arg1 proteins 257:264 misdirected proteins 245:264 misdirected proteins 245:264 Because misdirected proteins cannot function, protein sorting by COPII is critical for establishing and maintaining normal cell and tissue homeostasis. 29161034 9 79 from modification 1771:1782 arg1 pathway 1830:1836 the vertebrate COPII-dependent trafficking pathway 1787:1836 the vertebrate COPII-dependent trafficking pathway 1787:1836 Our results indicate that O-GlcNAc is a conserved and critical regulatory modification in the vertebrate COPII-dependent trafficking pathway. 29161034 2 80 theme tissue 369:374 arg1 homeostasis 376:386 normal cell and tissue homeostasis 353:386 homeostasis 376:386 Because misdirected proteins cannot function, protein sorting by COPII is critical for establishing and maintaining normal cell and tissue homeostasis. 29161034 7 81 theme chemical 1188:1195 arg1 approaches 1233:1242 chemical, biochemical, cellular, and genetic approaches 1188:1242 chemical, biochemical, cellular, and genetic approaches 1188:1242 Here, we use a combination of chemical, biochemical, cellular, and genetic approaches to demonstrate that site-specific O-GlcNAcylation of COPII proteins mediates their protein-protein interactions and modulates cargo secretion. 29161034 7 82 theme cellular 1211:1218 arg1 approaches 1233:1242 chemical, biochemical, cellular, and genetic approaches 1188:1242 chemical, biochemical, cellular, and genetic approaches 1188:1242 Here, we use a combination of chemical, biochemical, cellular, and genetic approaches to demonstrate that site-specific O-GlcNAcylation of COPII proteins mediates their protein-protein interactions and modulates cargo secretion. 24403076 0 0 theme glycosylation 132:144 arg1 loss 115:118 loss 115:118 loss of O-linked glycosylation 115:144 Ligand independence of the T618I mutation in the colony-stimulating factor 3 receptor (CSF3R) protein results from loss of O-linked glycosylation and increased receptor dimerization. 24403076 0 0 theme glycosylation 132:144 arg1 dimerization 169:180 increased receptor dimerization 150:180 increased receptor dimerization 150:180 Ligand independence of the T618I mutation in the colony-stimulating factor 3 receptor (CSF3R) protein results from loss of O-linked glycosylation and increased receptor dimerization. 24403076 0 1 theme receptor 160:167 arg1 dimerization 169:180 increased receptor dimerization 150:180 increased receptor dimerization 150:180 Ligand independence of the T618I mutation in the colony-stimulating factor 3 receptor (CSF3R) protein results from loss of O-linked glycosylation and increased receptor dimerization. 24403076 1 2 theme leukemia 388:395 arg1 types 379:383 other types 373:383 other types of leukemia 373:395 Mutations in the CSF3 granulocyte colony-stimulating factor receptor CSF3R have recently been found in a large percentage of patients with chronic neutrophilic leukemia and, more rarely, in other types of leukemia. 24403076 7 3 theme cluster 1473:1479 arg1 part 1439:1442 part 1439:1442 part of an O-linked glycosylation cluster 1439:1479 We show that the Thr-615 and Thr-618 sites of membrane-proximal mutations are part of an O-linked glycosylation cluster. 24403076 7 3 theme cluster 1473:1479 arg1 sites 1398:1402 the Thr-615 and Thr-618 sites 1374:1402 the Thr-615 and Thr-618 sites of membrane-proximal mutations 1374:1433 We show that the Thr-615 and Thr-618 sites of membrane-proximal mutations are part of an O-linked glycosylation cluster. 24403076 7 3 theme cluster 1473:1479 arg1 mutations 1425:1433 membrane-proximal mutations 1407:1433 membrane-proximal mutations 1407:1433 We show that the Thr-615 and Thr-618 sites of membrane-proximal mutations are part of an O-linked glycosylation cluster. 24403076 3 4 theme pathways 738:745 arg1 dysregulation 700:712 the dysregulation 696:712 the dysregulation of downstream signaling pathways 696:745 Although both classes of mutation have exhibited the capacity for cellular transformation, several aspects of this transformation, including the kinetics, the requirement for ligand, and the dysregulation of downstream signaling pathways, have all been shown to be discrepant between the mutation types, suggesting distinct mechanisms of activation. 24403076 3 4 theme pathways 738:745 arg1 kinetics 654:661 the kinetics 650:661 the kinetics 650:661 Although both classes of mutation have exhibited the capacity for cellular transformation, several aspects of this transformation, including the kinetics, the requirement for ligand, and the dysregulation of downstream signaling pathways, have all been shown to be discrepant between the mutation types, suggesting distinct mechanisms of activation. 24403076 3 4 theme pathways 738:745 arg1 requirement 668:678 the requirement 664:678 the requirement for ligand 664:689 Although both classes of mutation have exhibited the capacity for cellular transformation, several aspects of this transformation, including the kinetics, the requirement for ligand, and the dysregulation of downstream signaling pathways, have all been shown to be discrepant between the mutation types, suggesting distinct mechanisms of activation. 24403076 1 5 with patients 308:315 arg1 rarely 362:367 rarely 362:367 rarely 362:367 Mutations in the CSF3 granulocyte colony-stimulating factor receptor CSF3R have recently been found in a large percentage of patients with chronic neutrophilic leukemia and, more rarely, in other types of leukemia. 24403076 1 5 with patients 308:315 arg1 leukemia 343:350 chronic neutrophilic leukemia 322:350 chronic neutrophilic leukemia 322:350 Mutations in the CSF3 granulocyte colony-stimulating factor receptor CSF3R have recently been found in a large percentage of patients with chronic neutrophilic leukemia and, more rarely, in other types of leukemia. 24403076 7 6 theme O-linked 1450:1457 arg1 cluster 1473:1479 an O-linked glycosylation cluster 1447:1479 an O-linked glycosylation cluster 1447:1479 We show that the Thr-615 and Thr-618 sites of membrane-proximal mutations are part of an O-linked glycosylation cluster. 24403076 3 7 theme downstream 717:726 arg1 pathways 738:745 downstream signaling pathways 717:745 downstream signaling pathways 717:745 Although both classes of mutation have exhibited the capacity for cellular transformation, several aspects of this transformation, including the kinetics, the requirement for ligand, and the dysregulation of downstream signaling pathways, have all been shown to be discrepant between the mutation types, suggesting distinct mechanisms of activation. 24403076 4 8 theme truncation 865:874 arg1 mutations 876:884 CSF3R truncation mutations 859:884 CSF3R truncation mutations 859:884 CSF3R truncation mutations induce overexpression and ligand hypersensitivity of the receptor, likely because of the removal of motifs necessary for endocytosis and degradation. 24403076 10 9 theme receptor 1695:1702 arg1 activation 1704:1713 Cytokine receptor activation 1686:1713 Cytokine receptor activation through loss of O-glycosylation 1686:1745 Cytokine receptor activation through loss of O-glycosylation represents a novel avenue of aberrant signaling. 24403076 1 10 theme other 373:377 arg1 types 379:383 other types 373:383 other types of leukemia 373:395 Mutations in the CSF3 granulocyte colony-stimulating factor receptor CSF3R have recently been found in a large percentage of patients with chronic neutrophilic leukemia and, more rarely, in other types of leukemia. 24403076 8 11 gly O-glycosylation 1515:1529 arg1 CSF3R 1534:1538 CSF3R 1534:1538 CSF3R 1534:1538 Mutation at these sites prevents O-glycosylation of CSF3R and increases receptor dimerization. 24403076 6 12 with contrast 1206:1213 arg1 mutations 1237:1245 CSF3R truncation mutations 1220:1245 CSF3R truncation mutations 1220:1245 In contrast with CSF3R truncation mutations, membrane-proximal mutations do not exhibit overexpression and are capable of signaling in the absence of ligand. 24403076 7 13 theme membrane-proximal 1407:1423 arg1 mutations 1425:1433 membrane-proximal mutations 1407:1433 membrane-proximal mutations 1407:1433 We show that the Thr-615 and Thr-618 sites of membrane-proximal mutations are part of an O-linked glycosylation cluster. 24403076 0 14 theme O-linked 123:130 arg1 glycosylation 132:144 O-linked glycosylation 123:144 O-linked glycosylation 123:144 Ligand independence of the T618I mutation in the colony-stimulating factor 3 receptor (CSF3R) protein results from loss of O-linked glycosylation and increased receptor dimerization. 24403076 3 15 theme several 600:606 arg1 aspects 608:614 several aspects 600:614 several aspects 600:614 Although both classes of mutation have exhibited the capacity for cellular transformation, several aspects of this transformation, including the kinetics, the requirement for ligand, and the dysregulation of downstream signaling pathways, have all been shown to be discrepant between the mutation types, suggesting distinct mechanisms of activation. 24403076 3 15 theme several 600:606 arg1 dysregulation 700:712 the dysregulation 696:712 the dysregulation of downstream signaling pathways 696:745 Although both classes of mutation have exhibited the capacity for cellular transformation, several aspects of this transformation, including the kinetics, the requirement for ligand, and the dysregulation of downstream signaling pathways, have all been shown to be discrepant between the mutation types, suggesting distinct mechanisms of activation. 24403076 3 15 theme several 600:606 arg1 kinetics 654:661 the kinetics 650:661 the kinetics 650:661 Although both classes of mutation have exhibited the capacity for cellular transformation, several aspects of this transformation, including the kinetics, the requirement for ligand, and the dysregulation of downstream signaling pathways, have all been shown to be discrepant between the mutation types, suggesting distinct mechanisms of activation. 24403076 3 15 theme several 600:606 arg1 requirement 668:678 the requirement 664:678 the requirement for ligand 664:689 Although both classes of mutation have exhibited the capacity for cellular transformation, several aspects of this transformation, including the kinetics, the requirement for ligand, and the dysregulation of downstream signaling pathways, have all been shown to be discrepant between the mutation types, suggesting distinct mechanisms of activation. 24403076 11 16 theme truncation 1856:1865 arg1 mutations 1867:1875 the CSF3R membrane proximal and truncation mutations 1824:1875 mutations 1867:1875 Finally, the combination of the CSF3R membrane proximal and truncation mutations, as has been reported in some patients, leads to enhanced cellular transformation when compared with either mutation alone, underscoring their distinct mechanisms of action. 24403076 3 17 theme activation 847:856 arg1 mechanisms 833:842 distinct mechanisms 824:842 distinct mechanisms of activation 824:856 Although both classes of mutation have exhibited the capacity for cellular transformation, several aspects of this transformation, including the kinetics, the requirement for ligand, and the dysregulation of downstream signaling pathways, have all been shown to be discrepant between the mutation types, suggesting distinct mechanisms of activation. 24403076 4 18 theme necessary 993:1001 arg1 motifs 986:991 motifs 986:991 motifs necessary for endocytosis and degradation 986:1033 CSF3R truncation mutations induce overexpression and ligand hypersensitivity of the receptor, likely because of the removal of motifs necessary for endocytosis and degradation. 24403076 6 19 theme truncation 1226:1235 arg1 mutations 1237:1245 CSF3R truncation mutations 1220:1245 CSF3R truncation mutations 1220:1245 In contrast with CSF3R truncation mutations, membrane-proximal mutations do not exhibit overexpression and are capable of signaling in the absence of ligand. 24403076 11 20 theme proximal 1843:1850 arg1 combination 1809:1819 the combination 1805:1819 the combination of the CSF3R membrane proximal and truncation mutations 1805:1875 Finally, the combination of the CSF3R membrane proximal and truncation mutations, as has been reported in some patients, leads to enhanced cellular transformation when compared with either mutation alone, underscoring their distinct mechanisms of action. 24403076 0 21 theme colony-stimulating 49:66 arg1 CSF3R 87:91 CSF3R 87:91 CSF3R 87:91 Ligand independence of the T618I mutation in the colony-stimulating factor 3 receptor (CSF3R) protein results from loss of O-linked glycosylation and increased receptor dimerization. 24403076 0 21 theme colony-stimulating 49:66 arg1 receptor 77:84 colony-stimulating factor 3 receptor 49:84 the colony-stimulating factor 3 receptor (CSF3R) protein 45:100 Ligand independence of the T618I mutation in the colony-stimulating factor 3 receptor (CSF3R) protein results from loss of O-linked glycosylation and increased receptor dimerization. 24403076 1 22 theme neutrophilic 330:341 arg1 leukemia 343:350 chronic neutrophilic leukemia 322:350 chronic neutrophilic leukemia 322:350 Mutations in the CSF3 granulocyte colony-stimulating factor receptor CSF3R have recently been found in a large percentage of patients with chronic neutrophilic leukemia and, more rarely, in other types of leukemia. 24403076 3 23 theme transformation 624:637 arg1 aspects 608:614 several aspects 600:614 several aspects 600:614 Although both classes of mutation have exhibited the capacity for cellular transformation, several aspects of this transformation, including the kinetics, the requirement for ligand, and the dysregulation of downstream signaling pathways, have all been shown to be discrepant between the mutation types, suggesting distinct mechanisms of activation. 24403076 3 23 theme transformation 624:637 arg1 dysregulation 700:712 the dysregulation 696:712 the dysregulation of downstream signaling pathways 696:745 Although both classes of mutation have exhibited the capacity for cellular transformation, several aspects of this transformation, including the kinetics, the requirement for ligand, and the dysregulation of downstream signaling pathways, have all been shown to be discrepant between the mutation types, suggesting distinct mechanisms of activation. 24403076 3 23 theme transformation 624:637 arg1 kinetics 654:661 the kinetics 650:661 the kinetics 650:661 Although both classes of mutation have exhibited the capacity for cellular transformation, several aspects of this transformation, including the kinetics, the requirement for ligand, and the dysregulation of downstream signaling pathways, have all been shown to be discrepant between the mutation types, suggesting distinct mechanisms of activation. 24403076 3 23 theme transformation 624:637 arg1 requirement 668:678 the requirement 664:678 the requirement for ligand 664:689 Although both classes of mutation have exhibited the capacity for cellular transformation, several aspects of this transformation, including the kinetics, the requirement for ligand, and the dysregulation of downstream signaling pathways, have all been shown to be discrepant between the mutation types, suggesting distinct mechanisms of activation. 24403076 2 24 theme truncation 487:496 arg1 mutations 498:506 truncation mutations 487:506 truncation mutations 487:506 These CSF3R mutations fall into two distinct categories: membrane-proximal mutations and truncation mutations. 24403076 2 25 dep categories 443:452 arg1 mutations 498:506 truncation mutations 487:506 truncation mutations 487:506 These CSF3R mutations fall into two distinct categories: membrane-proximal mutations and truncation mutations. 24403076 2 25 dep categories 443:452 arg1 mutations 473:481 membrane-proximal mutations 455:481 membrane-proximal mutations 455:481 These CSF3R mutations fall into two distinct categories: membrane-proximal mutations and truncation mutations. 24403076 7 26 link O-linked 1450:1457 arg1 cluster 1473:1479 an O-linked glycosylation cluster 1447:1479 an O-linked glycosylation cluster 1447:1479 We show that the Thr-615 and Thr-618 sites of membrane-proximal mutations are part of an O-linked glycosylation cluster. 24403076 8 27 theme receptor 1554:1561 arg1 dimerization 1563:1574 receptor dimerization 1554:1574 receptor dimerization 1554:1574 Mutation at these sites prevents O-glycosylation of CSF3R and increases receptor dimerization. 24403076 5 28 theme mutations 1120:1128 arg1 activation 1088:1097 activation 1088:1097 activation of membrane-proximal mutations, which are much more commonly observed in chronic neutrophilic leukemia 1088:1200 In contrast, little is known about the mechanism of activation of membrane-proximal mutations, which are much more commonly observed in chronic neutrophilic leukemia. 24403076 2 29 theme CSF3R 404:408 arg1 mutations 410:418 These CSF3R mutations 398:418 These CSF3R mutations 398:418 These CSF3R mutations fall into two distinct categories: membrane-proximal mutations and truncation mutations. 24403076 2 30 theme distinct 434:441 arg1 categories 443:452 two distinct categories 430:452 two distinct categories: membrane-proximal mutations and truncation mutations 430:506 These CSF3R mutations fall into two distinct categories: membrane-proximal mutations and truncation mutations. 24403076 0 31 theme factor 68:73 arg1 CSF3R 87:91 CSF3R 87:91 CSF3R 87:91 Ligand independence of the T618I mutation in the colony-stimulating factor 3 receptor (CSF3R) protein results from loss of O-linked glycosylation and increased receptor dimerization. 24403076 0 31 theme factor 68:73 arg1 receptor 77:84 colony-stimulating factor 3 receptor 49:84 the colony-stimulating factor 3 receptor (CSF3R) protein 45:100 Ligand independence of the T618I mutation in the colony-stimulating factor 3 receptor (CSF3R) protein results from loss of O-linked glycosylation and increased receptor dimerization. 24403076 0 32 theme Ligand 0:5 arg1 independence 7:18 Ligand independence 0:18 Ligand independence of the T618I mutation in the colony-stimulating factor 3 receptor (CSF3R) protein 0:100 Ligand independence of the T618I mutation in the colony-stimulating factor 3 receptor (CSF3R) protein results from loss of O-linked glycosylation and increased receptor dimerization. 24403076 9 33 theme CSF3R 1651:1655 arg1 mutations 1675:1683 CSF3R membrane-proximal mutations 1651:1683 CSF3R membrane-proximal mutations 1651:1683 This increased dimerization explains the ligand-independent activation of CSF3R membrane-proximal mutations. 24403076 11 34 theme action 2043:2048 arg1 mechanisms 2029:2038 their distinct mechanisms 2014:2038 their distinct mechanisms of action 2014:2048 Finally, the combination of the CSF3R membrane proximal and truncation mutations, as has been reported in some patients, leads to enhanced cellular transformation when compared with either mutation alone, underscoring their distinct mechanisms of action. 24403076 1 35 theme large 288:292 arg1 percentage 294:303 a large percentage 286:303 a large percentage of patients with chronic neutrophilic leukemia and, more rarely, in other types of leukemia 286:395 Mutations in the CSF3 granulocyte colony-stimulating factor receptor CSF3R have recently been found in a large percentage of patients with chronic neutrophilic leukemia and, more rarely, in other types of leukemia. 24403076 9 36 theme mutations 1675:1683 arg1 activation 1637:1646 the ligand-independent activation 1614:1646 the ligand-independent activation of CSF3R membrane-proximal mutations 1614:1683 This increased dimerization explains the ligand-independent activation of CSF3R membrane-proximal mutations. 24403076 10 37 theme aberrant 1776:1783 arg1 signaling 1785:1793 aberrant signaling 1776:1793 aberrant signaling 1776:1793 Cytokine receptor activation through loss of O-glycosylation represents a novel avenue of aberrant signaling. 24403076 0 38 theme T618I 27:31 arg1 mutation 33:40 the T618I mutation 23:40 the T618I mutation 23:40 Ligand independence of the T618I mutation in the colony-stimulating factor 3 receptor (CSF3R) protein results from loss of O-linked glycosylation and increased receptor dimerization. 24403076 5 39 theme neutrophilic 1180:1191 arg1 leukemia 1193:1200 chronic neutrophilic leukemia 1172:1200 chronic neutrophilic leukemia 1172:1200 In contrast, little is known about the mechanism of activation of membrane-proximal mutations, which are much more commonly observed in chronic neutrophilic leukemia. 24403076 7 40 theme Thr-615 1378:1384 arg1 part 1439:1442 part 1439:1442 part of an O-linked glycosylation cluster 1439:1479 We show that the Thr-615 and Thr-618 sites of membrane-proximal mutations are part of an O-linked glycosylation cluster. 24403076 7 40 theme Thr-615 1378:1384 arg1 sites 1398:1402 the Thr-615 and Thr-618 sites 1374:1402 the Thr-615 and Thr-618 sites of membrane-proximal mutations 1374:1433 We show that the Thr-615 and Thr-618 sites of membrane-proximal mutations are part of an O-linked glycosylation cluster. 24403076 7 40 theme Thr-615 1378:1384 arg1 mutations 1425:1433 membrane-proximal mutations 1407:1433 membrane-proximal mutations 1407:1433 We show that the Thr-615 and Thr-618 sites of membrane-proximal mutations are part of an O-linked glycosylation cluster. 24403076 11 41 theme membrane 1834:1841 arg1 proximal 1843:1850 the CSF3R membrane proximal and truncation mutations 1824:1875 proximal 1843:1850 Finally, the combination of the CSF3R membrane proximal and truncation mutations, as has been reported in some patients, leads to enhanced cellular transformation when compared with either mutation alone, underscoring their distinct mechanisms of action. 24403076 11 42 theme cellular 1935:1942 arg1 transformation 1944:1957 enhanced cellular transformation 1926:1957 enhanced cellular transformation 1926:1957 Finally, the combination of the CSF3R membrane proximal and truncation mutations, as has been reported in some patients, leads to enhanced cellular transformation when compared with either mutation alone, underscoring their distinct mechanisms of action. 24403076 1 43 theme colony-stimulating 217:234 arg1 CSF3R 252:256 the CSF3 granulocyte colony-stimulating factor receptor CSF3R 196:256 the CSF3 granulocyte colony-stimulating factor receptor CSF3R 196:256 Mutations in the CSF3 granulocyte colony-stimulating factor receptor CSF3R have recently been found in a large percentage of patients with chronic neutrophilic leukemia and, more rarely, in other types of leukemia. 24403076 1 44 theme receptor 243:250 arg1 CSF3R 252:256 the CSF3 granulocyte colony-stimulating factor receptor CSF3R 196:256 the CSF3 granulocyte colony-stimulating factor receptor CSF3R 196:256 Mutations in the CSF3 granulocyte colony-stimulating factor receptor CSF3R have recently been found in a large percentage of patients with chronic neutrophilic leukemia and, more rarely, in other types of leukemia. 24403076 1 45 theme patients 308:315 arg1 percentage 294:303 a large percentage 286:303 a large percentage of patients with chronic neutrophilic leukemia and, more rarely, in other types of leukemia 286:395 Mutations in the CSF3 granulocyte colony-stimulating factor receptor CSF3R have recently been found in a large percentage of patients with chronic neutrophilic leukemia and, more rarely, in other types of leukemia. 24403076 3 46 theme mutation 534:541 arg1 classes 523:529 both classes 518:529 both classes of mutation 518:541 Although both classes of mutation have exhibited the capacity for cellular transformation, several aspects of this transformation, including the kinetics, the requirement for ligand, and the dysregulation of downstream signaling pathways, have all been shown to be discrepant between the mutation types, suggesting distinct mechanisms of activation. 24403076 7 47 theme glycosylation 1459:1471 arg1 cluster 1473:1479 an O-linked glycosylation cluster 1447:1479 an O-linked glycosylation cluster 1447:1479 We show that the Thr-615 and Thr-618 sites of membrane-proximal mutations are part of an O-linked glycosylation cluster. 24403076 3 48 theme signaling 728:736 arg1 pathways 738:745 downstream signaling pathways 717:745 downstream signaling pathways 717:745 Although both classes of mutation have exhibited the capacity for cellular transformation, several aspects of this transformation, including the kinetics, the requirement for ligand, and the dysregulation of downstream signaling pathways, have all been shown to be discrepant between the mutation types, suggesting distinct mechanisms of activation. 24403076 3 49 theme cellular 575:582 arg1 transformation 584:597 cellular transformation 575:597 cellular transformation 575:597 Although both classes of mutation have exhibited the capacity for cellular transformation, several aspects of this transformation, including the kinetics, the requirement for ligand, and the dysregulation of downstream signaling pathways, have all been shown to be discrepant between the mutation types, suggesting distinct mechanisms of activation. 24403076 4 50 theme CSF3R 859:863 arg1 mutations 876:884 CSF3R truncation mutations 859:884 CSF3R truncation mutations 859:884 CSF3R truncation mutations induce overexpression and ligand hypersensitivity of the receptor, likely because of the removal of motifs necessary for endocytosis and degradation. 24403076 10 51 theme Cytokine 1686:1693 arg1 activation 1704:1713 Cytokine receptor activation 1686:1713 Cytokine receptor activation through loss of O-glycosylation 1686:1745 Cytokine receptor activation through loss of O-glycosylation represents a novel avenue of aberrant signaling. 24403076 4 52 theme receptor 943:950 arg1 overexpression 893:906 overexpression 893:906 overexpression 893:906 CSF3R truncation mutations induce overexpression and ligand hypersensitivity of the receptor, likely because of the removal of motifs necessary for endocytosis and degradation. 24403076 4 52 theme receptor 943:950 arg1 hypersensitivity 919:934 ligand hypersensitivity 912:934 ligand hypersensitivity 912:934 CSF3R truncation mutations induce overexpression and ligand hypersensitivity of the receptor, likely because of the removal of motifs necessary for endocytosis and degradation. 24403076 10 53 theme O-glycosylation 1731:1745 arg1 loss 1723:1726 loss 1723:1726 loss of O-glycosylation 1723:1745 Cytokine receptor activation through loss of O-glycosylation represents a novel avenue of aberrant signaling. 24403076 5 54 theme activation 1088:1097 arg1 mechanism 1075:1083 the mechanism 1071:1083 the mechanism of activation of membrane-proximal mutations, which are much more commonly observed in chronic neutrophilic leukemia 1071:1200 In contrast, little is known about the mechanism of activation of membrane-proximal mutations, which are much more commonly observed in chronic neutrophilic leukemia. 24403076 7 55 theme mutations 1425:1433 arg1 part 1439:1442 part 1439:1442 part of an O-linked glycosylation cluster 1439:1479 We show that the Thr-615 and Thr-618 sites of membrane-proximal mutations are part of an O-linked glycosylation cluster. 24403076 7 55 theme mutations 1425:1433 arg1 sites 1398:1402 the Thr-615 and Thr-618 sites 1374:1402 the Thr-615 and Thr-618 sites of membrane-proximal mutations 1374:1433 We show that the Thr-615 and Thr-618 sites of membrane-proximal mutations are part of an O-linked glycosylation cluster. 24403076 7 55 theme mutations 1425:1433 arg1 mutations 1425:1433 membrane-proximal mutations 1407:1433 membrane-proximal mutations 1407:1433 We show that the Thr-615 and Thr-618 sites of membrane-proximal mutations are part of an O-linked glycosylation cluster. 24403076 11 56 theme enhanced 1926:1933 arg1 transformation 1944:1957 enhanced cellular transformation 1926:1957 enhanced cellular transformation 1926:1957 Finally, the combination of the CSF3R membrane proximal and truncation mutations, as has been reported in some patients, leads to enhanced cellular transformation when compared with either mutation alone, underscoring their distinct mechanisms of action. 24403076 6 57 theme ligand 1353:1358 arg1 absence 1342:1348 the absence 1338:1348 the absence of ligand 1338:1358 In contrast with CSF3R truncation mutations, membrane-proximal mutations do not exhibit overexpression and are capable of signaling in the absence of ligand. 24403076 5 58 theme membrane-proximal 1102:1118 arg1 mutations 1120:1128 membrane-proximal mutations 1102:1128 membrane-proximal mutations 1102:1128 In contrast, little is known about the mechanism of activation of membrane-proximal mutations, which are much more commonly observed in chronic neutrophilic leukemia. 24403076 4 59 theme ligand 912:917 arg1 hypersensitivity 919:934 ligand hypersensitivity 912:934 ligand hypersensitivity 912:934 CSF3R truncation mutations induce overexpression and ligand hypersensitivity of the receptor, likely because of the removal of motifs necessary for endocytosis and degradation. 24403076 6 60 theme membrane-proximal 1248:1264 arg1 mutations 1266:1274 membrane-proximal mutations 1248:1274 membrane-proximal mutations 1248:1274 In contrast with CSF3R truncation mutations, membrane-proximal mutations do not exhibit overexpression and are capable of signaling in the absence of ligand. 24403076 0 61 theme increased 150:158 arg1 dimerization 169:180 increased receptor dimerization 150:180 increased receptor dimerization 150:180 Ligand independence of the T618I mutation in the colony-stimulating factor 3 receptor (CSF3R) protein results from loss of O-linked glycosylation and increased receptor dimerization. 24403076 5 62 located observed 1160:1167 arg2 mutations 1120:1128 membrane-proximal mutations 1102:1128 membrane-proximal mutations 1102:1128 In contrast, little is known about the mechanism of activation of membrane-proximal mutations, which are much more commonly observed in chronic neutrophilic leukemia. 24403076 5 62 located observed 1160:1167 arg1 leukemia 1193:1200 chronic neutrophilic leukemia 1172:1200 chronic neutrophilic leukemia 1172:1200 In contrast, little is known about the mechanism of activation of membrane-proximal mutations, which are much more commonly observed in chronic neutrophilic leukemia. 24403076 8 63 theme CSF3R 1534:1538 arg1 O-glycosylation 1515:1529 O-glycosylation 1515:1529 O-glycosylation of CSF3R 1515:1538 Mutation at these sites prevents O-glycosylation of CSF3R and increases receptor dimerization. 24403076 7 64 theme Thr-618 1390:1396 arg1 part 1439:1442 part 1439:1442 part of an O-linked glycosylation cluster 1439:1479 We show that the Thr-615 and Thr-618 sites of membrane-proximal mutations are part of an O-linked glycosylation cluster. 24403076 7 64 theme Thr-618 1390:1396 arg1 sites 1398:1402 the Thr-615 and Thr-618 sites 1374:1402 the Thr-615 and Thr-618 sites of membrane-proximal mutations 1374:1433 We show that the Thr-615 and Thr-618 sites of membrane-proximal mutations are part of an O-linked glycosylation cluster. 24403076 7 64 theme Thr-618 1390:1396 arg1 mutations 1425:1433 membrane-proximal mutations 1407:1433 membrane-proximal mutations 1407:1433 We show that the Thr-615 and Thr-618 sites of membrane-proximal mutations are part of an O-linked glycosylation cluster. 24403076 11 65 theme mutations 1867:1875 arg1 combination 1809:1819 the combination 1805:1819 the combination of the CSF3R membrane proximal and truncation mutations 1805:1875 Finally, the combination of the CSF3R membrane proximal and truncation mutations, as has been reported in some patients, leads to enhanced cellular transformation when compared with either mutation alone, underscoring their distinct mechanisms of action. 24403076 8 66 from sites 1500:1504 arg1 Mutation 1482:1489 Mutation 1482:1489 Mutation at these sites 1482:1504 Mutation at these sites prevents O-glycosylation of CSF3R and increases receptor dimerization. 24403076 1 67 from Mutations 183:191 arg1 CSF3R 252:256 the CSF3 granulocyte colony-stimulating factor receptor CSF3R 196:256 the CSF3 granulocyte colony-stimulating factor receptor CSF3R 196:256 Mutations in the CSF3 granulocyte colony-stimulating factor receptor CSF3R have recently been found in a large percentage of patients with chronic neutrophilic leukemia and, more rarely, in other types of leukemia. 24403076 4 68 theme motifs 986:991 arg1 removal 975:981 the removal 971:981 the removal of motifs necessary for endocytosis and degradation 971:1033 CSF3R truncation mutations induce overexpression and ligand hypersensitivity of the receptor, likely because of the removal of motifs necessary for endocytosis and degradation. 24403076 6 69 theme CSF3R 1220:1224 arg1 mutations 1237:1245 CSF3R truncation mutations 1220:1245 CSF3R truncation mutations 1220:1245 In contrast with CSF3R truncation mutations, membrane-proximal mutations do not exhibit overexpression and are capable of signaling in the absence of ligand. 24403076 3 70 theme mutation 797:804 arg1 types 806:810 the mutation types 793:810 the mutation types 793:810 Although both classes of mutation have exhibited the capacity for cellular transformation, several aspects of this transformation, including the kinetics, the requirement for ligand, and the dysregulation of downstream signaling pathways, have all been shown to be discrepant between the mutation types, suggesting distinct mechanisms of activation. 24403076 0 71 theme receptor 77:84 arg1 protein 94:100 the colony-stimulating factor 3 receptor (CSF3R) protein 45:100 the colony-stimulating factor 3 receptor (CSF3R) protein 45:100 Ligand independence of the T618I mutation in the colony-stimulating factor 3 receptor (CSF3R) protein results from loss of O-linked glycosylation and increased receptor dimerization. 24403076 9 72 theme increased 1582:1590 arg1 dimerization 1592:1603 This increased dimerization 1577:1603 This increased dimerization 1577:1603 This increased dimerization explains the ligand-independent activation of CSF3R membrane-proximal mutations. 24403076 0 73 from independence 7:18 arg1 protein 94:100 the colony-stimulating factor 3 receptor (CSF3R) protein 45:100 the colony-stimulating factor 3 receptor (CSF3R) protein 45:100 Ligand independence of the T618I mutation in the colony-stimulating factor 3 receptor (CSF3R) protein results from loss of O-linked glycosylation and increased receptor dimerization. 24403076 3 74 theme distinct 824:831 arg1 mechanisms 833:842 distinct mechanisms 824:842 distinct mechanisms of activation 824:856 Although both classes of mutation have exhibited the capacity for cellular transformation, several aspects of this transformation, including the kinetics, the requirement for ligand, and the dysregulation of downstream signaling pathways, have all been shown to be discrepant between the mutation types, suggesting distinct mechanisms of activation. 24403076 11 75 dep leads 1917:1921 arg1 reported 1890:1897 reported 1890:1897 has been reported in some patients 1881:1914 Finally, the combination of the CSF3R membrane proximal and truncation mutations, as has been reported in some patients, leads to enhanced cellular transformation when compared with either mutation alone, underscoring their distinct mechanisms of action. 24403076 9 76 theme ligand-independent 1618:1635 arg1 activation 1637:1646 the ligand-independent activation 1614:1646 the ligand-independent activation of CSF3R membrane-proximal mutations 1614:1683 This increased dimerization explains the ligand-independent activation of CSF3R membrane-proximal mutations. 24403076 11 77 theme distinct 2020:2027 arg1 mechanisms 2029:2038 their distinct mechanisms 2014:2038 their distinct mechanisms of action 2014:2048 Finally, the combination of the CSF3R membrane proximal and truncation mutations, as has been reported in some patients, leads to enhanced cellular transformation when compared with either mutation alone, underscoring their distinct mechanisms of action. 24403076 9 78 theme membrane-proximal 1657:1673 arg1 mutations 1675:1683 CSF3R membrane-proximal mutations 1651:1683 CSF3R membrane-proximal mutations 1651:1683 This increased dimerization explains the ligand-independent activation of CSF3R membrane-proximal mutations. 24403076 10 79 theme signaling 1785:1793 arg1 avenue 1766:1771 a novel avenue 1758:1771 a novel avenue of aberrant signaling 1758:1793 Cytokine receptor activation through loss of O-glycosylation represents a novel avenue of aberrant signaling. 24403076 0 80 theme mutation 33:40 arg1 independence 7:18 Ligand independence 0:18 Ligand independence of the T618I mutation in the colony-stimulating factor 3 receptor (CSF3R) protein 0:100 Ligand independence of the T618I mutation in the colony-stimulating factor 3 receptor (CSF3R) protein results from loss of O-linked glycosylation and increased receptor dimerization. 24403076 0 81 link O-linked 123:130 arg1 glycosylation 132:144 O-linked glycosylation 123:144 O-linked glycosylation 123:144 Ligand independence of the T618I mutation in the colony-stimulating factor 3 receptor (CSF3R) protein results from loss of O-linked glycosylation and increased receptor dimerization. 24403076 2 82 theme membrane-proximal 455:471 arg1 mutations 473:481 membrane-proximal mutations 455:481 membrane-proximal mutations 455:481 These CSF3R mutations fall into two distinct categories: membrane-proximal mutations and truncation mutations. 24403076 5 83 theme chronic 1172:1178 arg1 leukemia 1193:1200 chronic neutrophilic leukemia 1172:1200 chronic neutrophilic leukemia 1172:1200 In contrast, little is known about the mechanism of activation of membrane-proximal mutations, which are much more commonly observed in chronic neutrophilic leukemia. 24403076 11 84 theme CSF3R 1828:1832 arg1 proximal 1843:1850 the CSF3R membrane proximal and truncation mutations 1824:1875 proximal 1843:1850 Finally, the combination of the CSF3R membrane proximal and truncation mutations, as has been reported in some patients, leads to enhanced cellular transformation when compared with either mutation alone, underscoring their distinct mechanisms of action. 24403076 1 85 theme chronic 322:328 arg1 leukemia 343:350 chronic neutrophilic leukemia 322:350 chronic neutrophilic leukemia 322:350 Mutations in the CSF3 granulocyte colony-stimulating factor receptor CSF3R have recently been found in a large percentage of patients with chronic neutrophilic leukemia and, more rarely, in other types of leukemia. 24403076 1 86 theme factor 236:241 arg1 CSF3R 252:256 the CSF3 granulocyte colony-stimulating factor receptor CSF3R 196:256 the CSF3 granulocyte colony-stimulating factor receptor CSF3R 196:256 Mutations in the CSF3 granulocyte colony-stimulating factor receptor CSF3R have recently been found in a large percentage of patients with chronic neutrophilic leukemia and, more rarely, in other types of leukemia. 24403076 1 87 located found 277:281 arg1 percentage 294:303 a large percentage 286:303 a large percentage of patients with chronic neutrophilic leukemia and, more rarely, in other types of leukemia 286:395 Mutations in the CSF3 granulocyte colony-stimulating factor receptor CSF3R have recently been found in a large percentage of patients with chronic neutrophilic leukemia and, more rarely, in other types of leukemia. 24403076 1 87 located found 277:281 arg2 Mutations 183:191 Mutations 183:191 Mutations in the CSF3 granulocyte colony-stimulating factor receptor CSF3R 183:256 Mutations in the CSF3 granulocyte colony-stimulating factor receptor CSF3R have recently been found in a large percentage of patients with chronic neutrophilic leukemia and, more rarely, in other types of leukemia. 24403076 10 88 theme novel 1760:1764 arg1 avenue 1766:1771 a novel avenue 1758:1771 a novel avenue of aberrant signaling 1758:1793 Cytokine receptor activation through loss of O-glycosylation represents a novel avenue of aberrant signaling. 26307167 9 0 theme EmaA 1484:1487 arg1 N-glycosylated 1527:1540 N-glycosylated 1527:1540 N-glycosylated 1527:1540 Here we show that the Kingella kingae Knh and the Aggregatibacter aphrophilus EmaA trimeric autotransporter proteins are N-glycosylated by novel homologues of the Haemophilus influenzae HMW1C glycosyltransferase, highlighting the first examples of trimeric autotransporters that are modified by HMW1C-like enzymes. 26307167 9 0 theme EmaA 1484:1487 arg1 proteins 1514:1521 the Kingella kingae Knh and the Aggregatibacter aphrophilus EmaA trimeric autotransporter proteins 1424:1521 the Kingella kingae Knh and the Aggregatibacter aphrophilus EmaA trimeric autotransporter proteins 1424:1521 Here we show that the Kingella kingae Knh and the Aggregatibacter aphrophilus EmaA trimeric autotransporter proteins are N-glycosylated by novel homologues of the Haemophilus influenzae HMW1C glycosyltransferase, highlighting the first examples of trimeric autotransporters that are modified by HMW1C-like enzymes. 26307167 4 1 theme acceptor 750:757 arg1 protein 759:765 an obvious acceptor protein 739:765 an obvious acceptor protein 739:765 In the present study, we examined Kingella kingae and Aggregatibacter aphrophilus homologues of HMW1C that are not encoded near a gene encoding an obvious acceptor protein. 26307167 9 2 theme Knh 1444:1446 arg1 N-glycosylated 1527:1540 N-glycosylated 1527:1540 N-glycosylated 1527:1540 Here we show that the Kingella kingae Knh and the Aggregatibacter aphrophilus EmaA trimeric autotransporter proteins are N-glycosylated by novel homologues of the Haemophilus influenzae HMW1C glycosyltransferase, highlighting the first examples of trimeric autotransporters that are modified by HMW1C-like enzymes. 26307167 9 2 theme Knh 1444:1446 arg1 proteins 1514:1521 the Kingella kingae Knh and the Aggregatibacter aphrophilus EmaA trimeric autotransporter proteins 1424:1521 the Kingella kingae Knh and the Aggregatibacter aphrophilus EmaA trimeric autotransporter proteins 1424:1521 Here we show that the Kingella kingae Knh and the Aggregatibacter aphrophilus EmaA trimeric autotransporter proteins are N-glycosylated by novel homologues of the Haemophilus influenzae HMW1C glycosyltransferase, highlighting the first examples of trimeric autotransporters that are modified by HMW1C-like enzymes. 26307167 3 3 theme sequential 555:564 arg1 transfer 566:573 sequential transfer 555:573 sequential transfer of hexose residues 555:592 In this system, HMW1 is modified in the cytoplasm by sequential transfer of hexose residues. 26307167 4 4 theme Kingella 629:636 arg1 homologues 677:686 Kingella kingae and Aggregatibacter aphrophilus homologues 629:686 Kingella kingae and Aggregatibacter aphrophilus homologues of HMW1C that are not encoded near a gene encoding an obvious acceptor protein 629:765 In the present study, we examined Kingella kingae and Aggregatibacter aphrophilus homologues of HMW1C that are not encoded near a gene encoding an obvious acceptor protein. 26307167 4 5 theme obvious 742:748 arg1 protein 759:765 an obvious acceptor protein 739:765 an obvious acceptor protein 739:765 In the present study, we examined Kingella kingae and Aggregatibacter aphrophilus homologues of HMW1C that are not encoded near a gene encoding an obvious acceptor protein. 26307167 9 6 mod modified 1689:1696 arg1 autotransporters 1663:1678 trimeric autotransporters 1654:1678 trimeric autotransporters that are modified by HMW1C-like enzymes 1654:1718 Here we show that the Kingella kingae Knh and the Aggregatibacter aphrophilus EmaA trimeric autotransporter proteins are N-glycosylated by novel homologues of the Haemophilus influenzae HMW1C glycosyltransferase, highlighting the first examples of trimeric autotransporters that are modified by HMW1C-like enzymes. 26307167 9 6 mod modified 1689:1696 arg3 enzymes 1712:1718 HMW1C-like enzymes 1701:1718 HMW1C-like enzymes 1701:1718 Here we show that the Kingella kingae Knh and the Aggregatibacter aphrophilus EmaA trimeric autotransporter proteins are N-glycosylated by novel homologues of the Haemophilus influenzae HMW1C glycosyltransferase, highlighting the first examples of trimeric autotransporters that are modified by HMW1C-like enzymes. 26307167 8 7 theme glycosylation 1349:1361 arg1 importance 1335:1344 the importance 1331:1344 the importance of glycosylation for proper function of bacterial proteins 1331:1403 IMPORTANCE: This work emphasizes the importance of glycosylation for proper function of bacterial proteins. 26307167 6 8 gly glycosylation 1050:1062 arg2 sites 1032:1036 multiple sites 1023:1036 multiple sites of N-linked glycosylation on Knh and EmaA 1023:1078 Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis revealed multiple sites of N-linked glycosylation on Knh and EmaA. 26307167 6 8 gly glycosylation 1050:1062 arg2 glycosylation 1050:1062 N-linked glycosylation 1041:1062 N-linked glycosylation 1041:1062 Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis revealed multiple sites of N-linked glycosylation on Knh and EmaA. 26307167 2 9 gly glycosylation 369:381 arg1 HMW1 407:410 the adhesive protein HMW1 386:410 the adhesive protein HMW1 386:410 The nontypeable Haemophilus influenzae glycosyltransferase HMW1C mediates unconventional N-linked glycosylation of the adhesive protein HMW1, which is encoded in a two-partner secretion system gene cluster that also encodes HMW1C. 26307167 5 10 dep Knh 880:882 arg1 proteins 937:944 trimeric autotransporter proteins 912:944 trimeric autotransporter proteins 912:944 We found both homologues to be functional glycosyltransferases and identified their substrates as the K. kingae Knh and the A. aphrophilus EmaA trimeric autotransporter proteins. 26307167 2 11 theme N-linked 360:367 arg1 glycosylation 369:381 unconventional N-linked glycosylation 345:381 unconventional N-linked glycosylation of the adhesive protein HMW1, which is encoded in a two-partner secretion system gene cluster that also encodes HMW1C 345:499 The nontypeable Haemophilus influenzae glycosyltransferase HMW1C mediates unconventional N-linked glycosylation of the adhesive protein HMW1, which is encoded in a two-partner secretion system gene cluster that also encodes HMW1C. 26307167 9 12 theme Haemophilus 1569:1579 arg1 glycosyltransferase 1598:1616 the Haemophilus influenzae HMW1C glycosyltransferase 1565:1616 the Haemophilus influenzae HMW1C glycosyltransferase 1565:1616 Here we show that the Kingella kingae Knh and the Aggregatibacter aphrophilus EmaA trimeric autotransporter proteins are N-glycosylated by novel homologues of the Haemophilus influenzae HMW1C glycosyltransferase, highlighting the first examples of trimeric autotransporters that are modified by HMW1C-like enzymes. 26307167 11 13 theme bacterial 1839:1847 arg1 pathogenicity 1849:1861 bacterial pathogenicity 1839:1861 bacterial pathogenicity 1839:1861 This work has relevance to our understanding of bacterial pathogenicity and expression of potential vaccine antigens. 26307167 7 14 theme human 1200:1204 arg1 cells 1217:1221 human epithelial cells 1200:1221 human epithelial cells 1200:1221 Without glycosylation, Knh and EmaA failed to facilitate wild-type levels of bacterial autoaggregation or adherence to human epithelial cells, establishing that glycosylation is essential for proper protein function. 26307167 2 15 theme unconventional 345:358 arg1 glycosylation 369:381 unconventional N-linked glycosylation 345:381 unconventional N-linked glycosylation of the adhesive protein HMW1, which is encoded in a two-partner secretion system gene cluster that also encodes HMW1C 345:499 The nontypeable Haemophilus influenzae glycosyltransferase HMW1C mediates unconventional N-linked glycosylation of the adhesive protein HMW1, which is encoded in a two-partner secretion system gene cluster that also encodes HMW1C. 26307167 9 16 theme glycosyltransferase 1598:1616 arg1 homologues 1551:1560 novel homologues 1545:1560 novel homologues of the Haemophilus influenzae HMW1C glycosyltransferase 1545:1616 Here we show that the Kingella kingae Knh and the Aggregatibacter aphrophilus EmaA trimeric autotransporter proteins are N-glycosylated by novel homologues of the Haemophilus influenzae HMW1C glycosyltransferase, highlighting the first examples of trimeric autotransporters that are modified by HMW1C-like enzymes. 26307167 6 17 theme spectrometry 981:992 arg1 analysis 1005:1012 Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis 947:1012 Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis 947:1012 Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis revealed multiple sites of N-linked glycosylation on Knh and EmaA. 26307167 7 18 theme epithelial 1206:1215 arg1 cells 1217:1221 human epithelial cells 1200:1221 human epithelial cells 1200:1221 Without glycosylation, Knh and EmaA failed to facilitate wild-type levels of bacterial autoaggregation or adherence to human epithelial cells, establishing that glycosylation is essential for proper protein function. 26307167 9 19 theme autotransporters 1663:1678 arg1 examples 1642:1649 the first examples 1632:1649 the first examples of trimeric autotransporters that are modified by HMW1C-like enzymes 1632:1718 Here we show that the Kingella kingae Knh and the Aggregatibacter aphrophilus EmaA trimeric autotransporter proteins are N-glycosylated by novel homologues of the Haemophilus influenzae HMW1C glycosyltransferase, highlighting the first examples of trimeric autotransporters that are modified by HMW1C-like enzymes. 26307167 2 20 dep Haemophilus 287:297 arg1 influenzae 299:308 influenzae 299:308 influenzae 299:308 The nontypeable Haemophilus influenzae glycosyltransferase HMW1C mediates unconventional N-linked glycosylation of the adhesive protein HMW1, which is encoded in a two-partner secretion system gene cluster that also encodes HMW1C. 26307167 0 21 theme N-Linked 15:22 arg1 Glycosylation 24:36 Unconventional N-Linked Glycosylation 0:36 Unconventional N-Linked Glycosylation 0:36 Unconventional N-Linked Glycosylation Promotes Trimeric Autotransporter Function in Kingella kingae and Aggregatibacter aphrophilus. 26307167 6 22 theme mass 976:979 arg1 LC-MS/MS 995:1002 LC-MS/MS 995:1002 LC-MS/MS 995:1002 Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis revealed multiple sites of N-linked glycosylation on Knh and EmaA. 26307167 6 22 theme mass 976:979 arg1 spectrometry 981:992 Liquid chromatography-tandem mass spectrometry 947:992 Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis 947:1012 Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis revealed multiple sites of N-linked glycosylation on Knh and EmaA. 26307167 7 23 theme adherence 1187:1195 arg1 levels 1148:1153 wild-type levels 1138:1153 wild-type levels of bacterial autoaggregation or adherence to human epithelial cells 1138:1221 Without glycosylation, Knh and EmaA failed to facilitate wild-type levels of bacterial autoaggregation or adherence to human epithelial cells, establishing that glycosylation is essential for proper protein function. 26307167 2 24 theme protein 399:405 arg1 HMW1 407:410 the adhesive protein HMW1 386:410 the adhesive protein HMW1 386:410 The nontypeable Haemophilus influenzae glycosyltransferase HMW1C mediates unconventional N-linked glycosylation of the adhesive protein HMW1, which is encoded in a two-partner secretion system gene cluster that also encodes HMW1C. 26307167 2 25 theme system 457:462 arg1 cluster 469:475 a two-partner secretion system gene cluster 433:475 a two-partner secretion system gene cluster that also encodes HMW1C 433:499 The nontypeable Haemophilus influenzae glycosyltransferase HMW1C mediates unconventional N-linked glycosylation of the adhesive protein HMW1, which is encoded in a two-partner secretion system gene cluster that also encodes HMW1C. 26307167 2 25 theme system 457:462 arg1 HMW1C 495:499 HMW1C 495:499 HMW1C 495:499 The nontypeable Haemophilus influenzae glycosyltransferase HMW1C mediates unconventional N-linked glycosylation of the adhesive protein HMW1, which is encoded in a two-partner secretion system gene cluster that also encodes HMW1C. 26307167 0 26 theme Unconventional 0:13 arg1 Glycosylation 24:36 Unconventional N-Linked Glycosylation 0:36 Unconventional N-Linked Glycosylation 0:36 Unconventional N-Linked Glycosylation Promotes Trimeric Autotransporter Function in Kingella kingae and Aggregatibacter aphrophilus. 26307167 11 27 theme vaccine 1891:1897 arg1 antigens 1899:1906 potential vaccine antigens 1881:1906 potential vaccine antigens 1881:1906 This work has relevance to our understanding of bacterial pathogenicity and expression of potential vaccine antigens. 26307167 2 28 theme adhesive 390:397 arg1 HMW1 407:410 the adhesive protein HMW1 386:410 the adhesive protein HMW1 386:410 The nontypeable Haemophilus influenzae glycosyltransferase HMW1C mediates unconventional N-linked glycosylation of the adhesive protein HMW1, which is encoded in a two-partner secretion system gene cluster that also encodes HMW1C. 26307167 11 29 contain has 1801:1803 arg1 work 1796:1799 This work 1791:1799 This work 1791:1799 This work has relevance to our understanding of bacterial pathogenicity and expression of potential vaccine antigens. 26307167 11 29 contain has 1801:1803 arg2 relevance 1805:1813 relevance 1805:1813 relevance 1805:1813 This work has relevance to our understanding of bacterial pathogenicity and expression of potential vaccine antigens. 26307167 2 30 theme secretion 447:455 arg1 system 457:462 a two-partner secretion system 433:462 a two-partner secretion system gene cluster that also encodes HMW1C 433:499 The nontypeable Haemophilus influenzae glycosyltransferase HMW1C mediates unconventional N-linked glycosylation of the adhesive protein HMW1, which is encoded in a two-partner secretion system gene cluster that also encodes HMW1C. 26307167 7 31 theme proper 1273:1278 arg1 function 1288:1295 proper protein function 1273:1295 proper protein function 1273:1295 Without glycosylation, Knh and EmaA failed to facilitate wild-type levels of bacterial autoaggregation or adherence to human epithelial cells, establishing that glycosylation is essential for proper protein function. 26307167 4 32 theme present 602:608 arg1 study 610:614 the present study 598:614 the present study 598:614 In the present study, we examined Kingella kingae and Aggregatibacter aphrophilus homologues of HMW1C that are not encoded near a gene encoding an obvious acceptor protein. 26307167 7 33 theme autoaggregation 1168:1182 arg1 levels 1148:1153 wild-type levels 1138:1153 wild-type levels of bacterial autoaggregation or adherence to human epithelial cells 1138:1221 Without glycosylation, Knh and EmaA failed to facilitate wild-type levels of bacterial autoaggregation or adherence to human epithelial cells, establishing that glycosylation is essential for proper protein function. 26307167 9 34 gly N-glycosylated 1527:1540 arg1 N-glycosylated 1527:1540 N-glycosylated 1527:1540 N-glycosylated 1527:1540 Here we show that the Kingella kingae Knh and the Aggregatibacter aphrophilus EmaA trimeric autotransporter proteins are N-glycosylated by novel homologues of the Haemophilus influenzae HMW1C glycosyltransferase, highlighting the first examples of trimeric autotransporters that are modified by HMW1C-like enzymes. 26307167 9 34 gly N-glycosylated 1527:1540 arg1 proteins 1514:1521 the Kingella kingae Knh and the Aggregatibacter aphrophilus EmaA trimeric autotransporter proteins 1424:1521 the Kingella kingae Knh and the Aggregatibacter aphrophilus EmaA trimeric autotransporter proteins 1424:1521 Here we show that the Kingella kingae Knh and the Aggregatibacter aphrophilus EmaA trimeric autotransporter proteins are N-glycosylated by novel homologues of the Haemophilus influenzae HMW1C glycosyltransferase, highlighting the first examples of trimeric autotransporters that are modified by HMW1C-like enzymes. 26307167 1 35 theme functional 230:239 arg1 diversity 241:249 the functional diversity 226:249 the functional diversity of their proteomes 226:268 Glycosylation is a widespread mechanism employed by both eukaryotes and bacteria to increase the functional diversity of their proteomes. 26307167 7 36 theme protein 1280:1286 arg1 function 1288:1295 proper protein function 1273:1295 proper protein function 1273:1295 Without glycosylation, Knh and EmaA failed to facilitate wild-type levels of bacterial autoaggregation or adherence to human epithelial cells, establishing that glycosylation is essential for proper protein function. 26307167 3 37 theme residues 585:592 arg1 transfer 566:573 sequential transfer 555:573 sequential transfer of hexose residues 555:592 In this system, HMW1 is modified in the cytoplasm by sequential transfer of hexose residues. 26307167 6 38 theme chromatography-tandem 954:974 arg1 LC-MS/MS 995:1002 LC-MS/MS 995:1002 LC-MS/MS 995:1002 Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis revealed multiple sites of N-linked glycosylation on Knh and EmaA. 26307167 6 38 theme chromatography-tandem 954:974 arg1 spectrometry 981:992 Liquid chromatography-tandem mass spectrometry 947:992 Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis 947:1012 Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis revealed multiple sites of N-linked glycosylation on Knh and EmaA. 26307167 9 39 theme HMW1C-like 1701:1710 arg1 enzymes 1712:1718 HMW1C-like enzymes 1701:1718 HMW1C-like enzymes 1701:1718 Here we show that the Kingella kingae Knh and the Aggregatibacter aphrophilus EmaA trimeric autotransporter proteins are N-glycosylated by novel homologues of the Haemophilus influenzae HMW1C glycosyltransferase, highlighting the first examples of trimeric autotransporters that are modified by HMW1C-like enzymes. 26307167 4 40 theme HMW1C 691:695 arg1 homologues 677:686 Kingella kingae and Aggregatibacter aphrophilus homologues 629:686 Kingella kingae and Aggregatibacter aphrophilus homologues of HMW1C that are not encoded near a gene encoding an obvious acceptor protein 629:765 In the present study, we examined Kingella kingae and Aggregatibacter aphrophilus homologues of HMW1C that are not encoded near a gene encoding an obvious acceptor protein. 26307167 0 41 theme Autotransporter 56:70 arg1 Function 72:79 Trimeric Autotransporter Function 47:79 Trimeric Autotransporter Function 47:79 Unconventional N-Linked Glycosylation Promotes Trimeric Autotransporter Function in Kingella kingae and Aggregatibacter aphrophilus. 26307167 2 42 link N-linked 360:367 arg1 glycosylation 369:381 unconventional N-linked glycosylation 345:381 unconventional N-linked glycosylation of the adhesive protein HMW1, which is encoded in a two-partner secretion system gene cluster that also encodes HMW1C 345:499 The nontypeable Haemophilus influenzae glycosyltransferase HMW1C mediates unconventional N-linked glycosylation of the adhesive protein HMW1, which is encoded in a two-partner secretion system gene cluster that also encodes HMW1C. 26307167 9 43 theme trimeric 1654:1661 arg1 autotransporters 1663:1678 trimeric autotransporters 1654:1678 trimeric autotransporters that are modified by HMW1C-like enzymes 1654:1718 Here we show that the Kingella kingae Knh and the Aggregatibacter aphrophilus EmaA trimeric autotransporter proteins are N-glycosylated by novel homologues of the Haemophilus influenzae HMW1C glycosyltransferase, highlighting the first examples of trimeric autotransporters that are modified by HMW1C-like enzymes. 26307167 6 44 theme Liquid 947:952 arg1 LC-MS/MS 995:1002 LC-MS/MS 995:1002 LC-MS/MS 995:1002 Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis revealed multiple sites of N-linked glycosylation on Knh and EmaA. 26307167 6 44 theme Liquid 947:952 arg1 spectrometry 981:992 Liquid chromatography-tandem mass spectrometry 947:992 Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis 947:1012 Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis revealed multiple sites of N-linked glycosylation on Knh and EmaA. 26307167 2 45 theme nontypeable 275:285 arg1 HMW1C 330:334 The nontypeable Haemophilus influenzae glycosyltransferase HMW1C 271:334 The nontypeable Haemophilus influenzae glycosyltransferase HMW1C 271:334 The nontypeable Haemophilus influenzae glycosyltransferase HMW1C mediates unconventional N-linked glycosylation of the adhesive protein HMW1, which is encoded in a two-partner secretion system gene cluster that also encodes HMW1C. 26307167 8 46 theme proper 1367:1372 arg1 function 1374:1381 proper function 1367:1381 proper function of bacterial proteins 1367:1403 IMPORTANCE: This work emphasizes the importance of glycosylation for proper function of bacterial proteins. 26307167 5 47 theme trimeric 912:919 arg1 proteins 937:944 trimeric autotransporter proteins 912:944 trimeric autotransporter proteins 912:944 We found both homologues to be functional glycosyltransferases and identified their substrates as the K. kingae Knh and the A. aphrophilus EmaA trimeric autotransporter proteins. 26307167 0 48 theme Trimeric 47:54 arg1 Function 72:79 Trimeric Autotransporter Function 47:79 Trimeric Autotransporter Function 47:79 Unconventional N-Linked Glycosylation Promotes Trimeric Autotransporter Function in Kingella kingae and Aggregatibacter aphrophilus. 26307167 6 49 theme glycosylation 1050:1062 arg1 sites 1032:1036 multiple sites 1023:1036 multiple sites of N-linked glycosylation on Knh and EmaA 1023:1078 Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis revealed multiple sites of N-linked glycosylation on Knh and EmaA. 26307167 6 49 theme glycosylation 1050:1062 arg1 glycosylation 1050:1062 N-linked glycosylation 1041:1062 N-linked glycosylation 1041:1062 Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis revealed multiple sites of N-linked glycosylation on Knh and EmaA. 26307167 7 50 theme bacterial 1158:1166 arg1 autoaggregation 1168:1182 bacterial autoaggregation 1158:1182 bacterial autoaggregation 1158:1182 Without glycosylation, Knh and EmaA failed to facilitate wild-type levels of bacterial autoaggregation or adherence to human epithelial cells, establishing that glycosylation is essential for proper protein function. 26307167 4 51 dep Kingella 629:636 arg1 kingae 638:643 kingae 638:643 kingae 638:643 In the present study, we examined Kingella kingae and Aggregatibacter aphrophilus homologues of HMW1C that are not encoded near a gene encoding an obvious acceptor protein. 26307167 5 52 theme autotransporter 921:935 arg1 proteins 937:944 trimeric autotransporter proteins 912:944 trimeric autotransporter proteins 912:944 We found both homologues to be functional glycosyltransferases and identified their substrates as the K. kingae Knh and the A. aphrophilus EmaA trimeric autotransporter proteins. 26307167 6 53 theme N-linked 1041:1048 arg1 glycosylation 1050:1062 N-linked glycosylation 1041:1062 N-linked glycosylation 1041:1062 Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis revealed multiple sites of N-linked glycosylation on Knh and EmaA. 26307167 7 54 theme wild-type 1138:1146 arg1 levels 1148:1153 wild-type levels 1138:1153 wild-type levels of bacterial autoaggregation or adherence to human epithelial cells 1138:1221 Without glycosylation, Knh and EmaA failed to facilitate wild-type levels of bacterial autoaggregation or adherence to human epithelial cells, establishing that glycosylation is essential for proper protein function. 26307167 9 55 theme first 1636:1640 arg1 examples 1642:1649 the first examples 1632:1649 the first examples of trimeric autotransporters that are modified by HMW1C-like enzymes 1632:1718 Here we show that the Kingella kingae Knh and the Aggregatibacter aphrophilus EmaA trimeric autotransporter proteins are N-glycosylated by novel homologues of the Haemophilus influenzae HMW1C glycosyltransferase, highlighting the first examples of trimeric autotransporters that are modified by HMW1C-like enzymes. 26307167 10 56 theme adhesive 1772:1779 arg1 activity 1781:1788 adhesive activity 1772:1788 adhesive activity 1772:1788 In the absence of glycosylation, Knh and EmaA lack adhesive activity. 26307167 9 57 theme autotransporter 1498:1512 arg1 N-glycosylated 1527:1540 N-glycosylated 1527:1540 N-glycosylated 1527:1540 Here we show that the Kingella kingae Knh and the Aggregatibacter aphrophilus EmaA trimeric autotransporter proteins are N-glycosylated by novel homologues of the Haemophilus influenzae HMW1C glycosyltransferase, highlighting the first examples of trimeric autotransporters that are modified by HMW1C-like enzymes. 26307167 9 57 theme autotransporter 1498:1512 arg1 proteins 1514:1521 the Kingella kingae Knh and the Aggregatibacter aphrophilus EmaA trimeric autotransporter proteins 1424:1521 the Kingella kingae Knh and the Aggregatibacter aphrophilus EmaA trimeric autotransporter proteins 1424:1521 Here we show that the Kingella kingae Knh and the Aggregatibacter aphrophilus EmaA trimeric autotransporter proteins are N-glycosylated by novel homologues of the Haemophilus influenzae HMW1C glycosyltransferase, highlighting the first examples of trimeric autotransporters that are modified by HMW1C-like enzymes. 26307167 6 58 from sites 1032:1036 arg1 Knh 1067:1069 Knh 1067:1069 Knh 1067:1069 Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis revealed multiple sites of N-linked glycosylation on Knh and EmaA. 26307167 6 58 from sites 1032:1036 arg1 EmaA 1075:1078 EmaA 1075:1078 EmaA 1075:1078 Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis revealed multiple sites of N-linked glycosylation on Knh and EmaA. 26307167 11 59 theme antigens 1899:1906 arg1 expression 1867:1876 expression 1867:1876 expression of potential vaccine antigens 1867:1906 This work has relevance to our understanding of bacterial pathogenicity and expression of potential vaccine antigens. 26307167 11 59 theme antigens 1899:1906 arg1 understanding 1822:1834 our understanding 1818:1834 our understanding of bacterial pathogenicity 1818:1861 This work has relevance to our understanding of bacterial pathogenicity and expression of potential vaccine antigens. 26307167 7 60 gly glycosylation 1242:1254 arg1 protein 1280:1286 proper protein function 1273:1295 proper protein function 1273:1295 Without glycosylation, Knh and EmaA failed to facilitate wild-type levels of bacterial autoaggregation or adherence to human epithelial cells, establishing that glycosylation is essential for proper protein function. 26307167 1 61 theme widespread 152:161 arg1 mechanism 163:171 a widespread mechanism 150:171 a widespread mechanism employed by both eukaryotes and bacteria to increase the functional diversity of their proteomes 150:268 Glycosylation is a widespread mechanism employed by both eukaryotes and bacteria to increase the functional diversity of their proteomes. 26307167 1 61 theme widespread 152:161 arg1 Glycosylation 133:145 Glycosylation 133:145 Glycosylation 133:145 Glycosylation is a widespread mechanism employed by both eukaryotes and bacteria to increase the functional diversity of their proteomes. 26307167 6 62 link N-linked 1041:1048 arg1 glycosylation 1050:1062 N-linked glycosylation 1041:1062 N-linked glycosylation 1041:1062 Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis revealed multiple sites of N-linked glycosylation on Knh and EmaA. 26307167 11 63 theme pathogenicity 1849:1861 arg1 expression 1867:1876 expression 1867:1876 expression of potential vaccine antigens 1867:1906 This work has relevance to our understanding of bacterial pathogenicity and expression of potential vaccine antigens. 26307167 11 63 theme pathogenicity 1849:1861 arg1 understanding 1822:1834 our understanding 1818:1834 our understanding of bacterial pathogenicity 1818:1861 This work has relevance to our understanding of bacterial pathogenicity and expression of potential vaccine antigens. 26307167 9 64 dep Haemophilus 1569:1579 arg1 influenzae 1581:1590 influenzae 1581:1590 influenzae 1581:1590 Here we show that the Kingella kingae Knh and the Aggregatibacter aphrophilus EmaA trimeric autotransporter proteins are N-glycosylated by novel homologues of the Haemophilus influenzae HMW1C glycosyltransferase, highlighting the first examples of trimeric autotransporters that are modified by HMW1C-like enzymes. 26307167 10 65 theme glycosylation 1739:1751 arg1 absence 1728:1734 the absence 1724:1734 the absence of glycosylation 1724:1751 In the absence of glycosylation, Knh and EmaA lack adhesive activity. 26307167 3 66 mod modified 526:533 arg1 HMW1 518:521 HMW1 518:521 HMW1 518:521 In this system, HMW1 is modified in the cytoplasm by sequential transfer of hexose residues. 26307167 3 66 mod modified 526:533 arg3 transfer 566:573 sequential transfer 555:573 sequential transfer of hexose residues 555:592 In this system, HMW1 is modified in the cytoplasm by sequential transfer of hexose residues. 26307167 1 67 theme proteomes 260:268 arg1 diversity 241:249 the functional diversity 226:249 the functional diversity of their proteomes 226:268 Glycosylation is a widespread mechanism employed by both eukaryotes and bacteria to increase the functional diversity of their proteomes. 26307167 11 68 theme potential 1881:1889 arg1 antigens 1899:1906 potential vaccine antigens 1881:1906 potential vaccine antigens 1881:1906 This work has relevance to our understanding of bacterial pathogenicity and expression of potential vaccine antigens. 26307167 2 69 theme glycosyltransferase 310:328 arg1 HMW1C 330:334 The nontypeable Haemophilus influenzae glycosyltransferase HMW1C 271:334 The nontypeable Haemophilus influenzae glycosyltransferase HMW1C 271:334 The nontypeable Haemophilus influenzae glycosyltransferase HMW1C mediates unconventional N-linked glycosylation of the adhesive protein HMW1, which is encoded in a two-partner secretion system gene cluster that also encodes HMW1C. 26307167 2 70 theme HMW1 407:410 arg1 glycosylation 369:381 unconventional N-linked glycosylation 345:381 unconventional N-linked glycosylation of the adhesive protein HMW1, which is encoded in a two-partner secretion system gene cluster that also encodes HMW1C 345:499 The nontypeable Haemophilus influenzae glycosyltransferase HMW1C mediates unconventional N-linked glycosylation of the adhesive protein HMW1, which is encoded in a two-partner secretion system gene cluster that also encodes HMW1C. 26307167 4 71 theme Aggregatibacter 649:663 arg1 homologues 677:686 Kingella kingae and Aggregatibacter aphrophilus homologues 629:686 Kingella kingae and Aggregatibacter aphrophilus homologues of HMW1C that are not encoded near a gene encoding an obvious acceptor protein 629:765 In the present study, we examined Kingella kingae and Aggregatibacter aphrophilus homologues of HMW1C that are not encoded near a gene encoding an obvious acceptor protein. 26307167 5 72 theme functional 799:808 arg1 glycosyltransferases 810:829 functional glycosyltransferases 799:829 functional glycosyltransferases 799:829 We found both homologues to be functional glycosyltransferases and identified their substrates as the K. kingae Knh and the A. aphrophilus EmaA trimeric autotransporter proteins. 26307167 4 73 dep Aggregatibacter 649:663 arg1 aphrophilus 665:675 aphrophilus 665:675 aphrophilus 665:675 In the present study, we examined Kingella kingae and Aggregatibacter aphrophilus homologues of HMW1C that are not encoded near a gene encoding an obvious acceptor protein. 26307167 8 74 theme proteins 1396:1403 arg1 function 1374:1381 proper function 1367:1381 proper function of bacterial proteins 1367:1403 IMPORTANCE: This work emphasizes the importance of glycosylation for proper function of bacterial proteins. 26307167 8 75 theme bacterial 1386:1394 arg1 proteins 1396:1403 bacterial proteins 1386:1403 bacterial proteins 1386:1403 IMPORTANCE: This work emphasizes the importance of glycosylation for proper function of bacterial proteins. 26307167 2 76 theme two-partner 435:445 arg1 system 457:462 a two-partner secretion system 433:462 a two-partner secretion system gene cluster that also encodes HMW1C 433:499 The nontypeable Haemophilus influenzae glycosyltransferase HMW1C mediates unconventional N-linked glycosylation of the adhesive protein HMW1, which is encoded in a two-partner secretion system gene cluster that also encodes HMW1C. 26307167 2 77 theme gene 464:467 arg1 cluster 469:475 a two-partner secretion system gene cluster 433:475 a two-partner secretion system gene cluster that also encodes HMW1C 433:499 The nontypeable Haemophilus influenzae glycosyltransferase HMW1C mediates unconventional N-linked glycosylation of the adhesive protein HMW1, which is encoded in a two-partner secretion system gene cluster that also encodes HMW1C. 26307167 2 77 theme gene 464:467 arg1 HMW1C 495:499 HMW1C 495:499 HMW1C 495:499 The nontypeable Haemophilus influenzae glycosyltransferase HMW1C mediates unconventional N-linked glycosylation of the adhesive protein HMW1, which is encoded in a two-partner secretion system gene cluster that also encodes HMW1C. 26307167 9 78 theme HMW1C 1592:1596 arg1 glycosyltransferase 1598:1616 the Haemophilus influenzae HMW1C glycosyltransferase 1565:1616 the Haemophilus influenzae HMW1C glycosyltransferase 1565:1616 Here we show that the Kingella kingae Knh and the Aggregatibacter aphrophilus EmaA trimeric autotransporter proteins are N-glycosylated by novel homologues of the Haemophilus influenzae HMW1C glycosyltransferase, highlighting the first examples of trimeric autotransporters that are modified by HMW1C-like enzymes. 26307167 6 79 theme multiple 1023:1030 arg1 sites 1032:1036 multiple sites 1023:1036 multiple sites of N-linked glycosylation on Knh and EmaA 1023:1078 Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis revealed multiple sites of N-linked glycosylation on Knh and EmaA. 26307167 6 79 theme multiple 1023:1030 arg1 glycosylation 1050:1062 N-linked glycosylation 1041:1062 N-linked glycosylation 1041:1062 Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis revealed multiple sites of N-linked glycosylation on Knh and EmaA. 26307167 2 80 theme Haemophilus 287:297 arg1 HMW1C 330:334 The nontypeable Haemophilus influenzae glycosyltransferase HMW1C 271:334 The nontypeable Haemophilus influenzae glycosyltransferase HMW1C 271:334 The nontypeable Haemophilus influenzae glycosyltransferase HMW1C mediates unconventional N-linked glycosylation of the adhesive protein HMW1, which is encoded in a two-partner secretion system gene cluster that also encodes HMW1C. 26307167 3 81 theme hexose 578:583 arg1 residues 585:592 hexose residues 578:592 hexose residues 578:592 In this system, HMW1 is modified in the cytoplasm by sequential transfer of hexose residues. 26307167 9 82 theme novel 1545:1549 arg1 homologues 1551:1560 novel homologues 1545:1560 novel homologues of the Haemophilus influenzae HMW1C glycosyltransferase 1545:1616 Here we show that the Kingella kingae Knh and the Aggregatibacter aphrophilus EmaA trimeric autotransporter proteins are N-glycosylated by novel homologues of the Haemophilus influenzae HMW1C glycosyltransferase, highlighting the first examples of trimeric autotransporters that are modified by HMW1C-like enzymes. 26307167 9 83 theme trimeric 1489:1496 arg1 N-glycosylated 1527:1540 N-glycosylated 1527:1540 N-glycosylated 1527:1540 Here we show that the Kingella kingae Knh and the Aggregatibacter aphrophilus EmaA trimeric autotransporter proteins are N-glycosylated by novel homologues of the Haemophilus influenzae HMW1C glycosyltransferase, highlighting the first examples of trimeric autotransporters that are modified by HMW1C-like enzymes. 26307167 9 83 theme trimeric 1489:1496 arg1 proteins 1514:1521 the Kingella kingae Knh and the Aggregatibacter aphrophilus EmaA trimeric autotransporter proteins 1424:1521 the Kingella kingae Knh and the Aggregatibacter aphrophilus EmaA trimeric autotransporter proteins 1424:1521 Here we show that the Kingella kingae Knh and the Aggregatibacter aphrophilus EmaA trimeric autotransporter proteins are N-glycosylated by novel homologues of the Haemophilus influenzae HMW1C glycosyltransferase, highlighting the first examples of trimeric autotransporters that are modified by HMW1C-like enzymes. 28659383 1 0 link O-linked 82:89 arg1 N-acetylglucosamine 91:109 O-linked N-acetylglucosamine 82:109 O-linked N-acetylglucosamine (O-GlcNAc) 82:120 O-linked N-acetylglucosamine (O-GlcNAc) is an essential and dynamic post-translational modification found on hundreds of nucleocytoplasmic proteins in metazoa. 28659383 1 0 link O-linked 82:89 arg1 modification 169:180 an essential and dynamic post-translational modification 125:180 an essential and dynamic post-translational modification found on hundreds of nucleocytoplasmic proteins in metazoa 125:239 O-linked N-acetylglucosamine (O-GlcNAc) is an essential and dynamic post-translational modification found on hundreds of nucleocytoplasmic proteins in metazoa. 28659383 1 0 link O-linked 82:89 arg1 O-GlcNAc 112:119 O-GlcNAc 112:119 O-GlcNAc 112:119 O-linked N-acetylglucosamine (O-GlcNAc) is an essential and dynamic post-translational modification found on hundreds of nucleocytoplasmic proteins in metazoa. 28659383 4 1 theme extended 886:893 arg1 conformation 895:906 an extended conformation C-terminal 883:917 an extended conformation C-terminal of the O-GlcNAc target site 883:945 Confirmed by mutagenesis, this interaction suggests that glycosylation substrate specificity is achieved by recognition of a degenerate sequon in the active site combined with an extended conformation C-terminal of the O-GlcNAc target site. 28659383 1 2 theme post-translational 150:167 arg1 N-acetylglucosamine 91:109 O-linked N-acetylglucosamine 82:109 O-linked N-acetylglucosamine (O-GlcNAc) 82:120 O-linked N-acetylglucosamine (O-GlcNAc) is an essential and dynamic post-translational modification found on hundreds of nucleocytoplasmic proteins in metazoa. 28659383 1 2 theme post-translational 150:167 arg1 modification 169:180 an essential and dynamic post-translational modification 125:180 an essential and dynamic post-translational modification found on hundreds of nucleocytoplasmic proteins in metazoa 125:239 O-linked N-acetylglucosamine (O-GlcNAc) is an essential and dynamic post-translational modification found on hundreds of nucleocytoplasmic proteins in metazoa. 28659383 2 3 from serines/threonines 438:455 arg1 proteome 473:480 the metazoan proteome 460:480 the metazoan proteome 460:480 Although a single enzyme, O-GlcNAc transferase (OGT), generates the entire cytosolic O-GlcNAc proteome, it is not understood how it recognizes its protein substrates, targeting only a fraction of serines/threonines in the metazoan proteome for glycosylation. 28659383 3 4 theme OGT 702:704 arg1 repeats 691:697 the tetratricopeptide repeats 669:697 the tetratricopeptide repeats of OGT 669:704 We describe a trapped complex of human OGT with the C-terminal domain of TAB1, a key innate immunity-signalling O-GlcNAc protein, revealing extensive interactions with the tetratricopeptide repeats of OGT. 28659383 4 5 theme C-terminal 908:917 arg1 conformation 895:906 an extended conformation C-terminal 883:917 an extended conformation C-terminal of the O-GlcNAc target site 883:945 Confirmed by mutagenesis, this interaction suggests that glycosylation substrate specificity is achieved by recognition of a degenerate sequon in the active site combined with an extended conformation C-terminal of the O-GlcNAc target site. 28659383 3 6 theme OGT 540:542 arg1 complex 523:529 a trapped complex 513:529 a trapped complex of human OGT with the C-terminal domain of TAB1, a key innate immunity-signalling O-GlcNAc protein 513:628 We describe a trapped complex of human OGT with the C-terminal domain of TAB1, a key innate immunity-signalling O-GlcNAc protein, revealing extensive interactions with the tetratricopeptide repeats of OGT. 28659383 2 7 theme cytosolic 317:325 arg1 proteome 336:343 the entire cytosolic O-GlcNAc proteome 306:343 the entire cytosolic O-GlcNAc proteome 306:343 Although a single enzyme, O-GlcNAc transferase (OGT), generates the entire cytosolic O-GlcNAc proteome, it is not understood how it recognizes its protein substrates, targeting only a fraction of serines/threonines in the metazoan proteome for glycosylation. 28659383 3 8 with complex 523:529 arg1 TAB1 574:577 TAB1 574:577 TAB1 574:577 We describe a trapped complex of human OGT with the C-terminal domain of TAB1, a key innate immunity-signalling O-GlcNAc protein, revealing extensive interactions with the tetratricopeptide repeats of OGT. 28659383 3 8 with complex 523:529 arg1 domain 564:569 the C-terminal domain 549:569 the C-terminal domain of TAB1, a key innate immunity-signalling O-GlcNAc protein 549:628 We describe a trapped complex of human OGT with the C-terminal domain of TAB1, a key innate immunity-signalling O-GlcNAc protein, revealing extensive interactions with the tetratricopeptide repeats of OGT. 28659383 4 9 theme substrate 778:786 arg1 specificity 788:798 glycosylation substrate specificity 764:798 glycosylation substrate specificity 764:798 Confirmed by mutagenesis, this interaction suggests that glycosylation substrate specificity is achieved by recognition of a degenerate sequon in the active site combined with an extended conformation C-terminal of the O-GlcNAc target site. 28659383 2 10 theme O-GlcNAc 327:334 arg1 proteome 336:343 the entire cytosolic O-GlcNAc proteome 306:343 the entire cytosolic O-GlcNAc proteome 306:343 Although a single enzyme, O-GlcNAc transferase (OGT), generates the entire cytosolic O-GlcNAc proteome, it is not understood how it recognizes its protein substrates, targeting only a fraction of serines/threonines in the metazoan proteome for glycosylation. 28659383 2 11 theme protein 389:395 arg1 substrates 397:406 its protein substrates 385:406 its protein substrates 385:406 Although a single enzyme, O-GlcNAc transferase (OGT), generates the entire cytosolic O-GlcNAc proteome, it is not understood how it recognizes its protein substrates, targeting only a fraction of serines/threonines in the metazoan proteome for glycosylation. 28659383 2 12 from proteome 473:480 arg1 fraction 426:433 only a fraction 419:433 only a fraction of serines/threonines in the metazoan proteome 419:480 Although a single enzyme, O-GlcNAc transferase (OGT), generates the entire cytosolic O-GlcNAc proteome, it is not understood how it recognizes its protein substrates, targeting only a fraction of serines/threonines in the metazoan proteome for glycosylation. 28659383 4 13 theme active 857:862 arg1 site 864:867 the active site 853:867 the active site combined with an extended conformation C-terminal of the O-GlcNAc target site 853:945 Confirmed by mutagenesis, this interaction suggests that glycosylation substrate specificity is achieved by recognition of a degenerate sequon in the active site combined with an extended conformation C-terminal of the O-GlcNAc target site. 28659383 3 14 theme human 534:538 arg1 OGT 540:542 human OGT 534:542 human OGT 534:542 We describe a trapped complex of human OGT with the C-terminal domain of TAB1, a key innate immunity-signalling O-GlcNAc protein, revealing extensive interactions with the tetratricopeptide repeats of OGT. 28659383 2 15 theme serines/threonines 438:455 arg1 fraction 426:433 only a fraction 419:433 only a fraction of serines/threonines in the metazoan proteome 419:480 Although a single enzyme, O-GlcNAc transferase (OGT), generates the entire cytosolic O-GlcNAc proteome, it is not understood how it recognizes its protein substrates, targeting only a fraction of serines/threonines in the metazoan proteome for glycosylation. 28659383 1 16 theme O-linked 82:89 arg1 N-acetylglucosamine 91:109 O-linked N-acetylglucosamine 82:109 O-linked N-acetylglucosamine (O-GlcNAc) 82:120 O-linked N-acetylglucosamine (O-GlcNAc) is an essential and dynamic post-translational modification found on hundreds of nucleocytoplasmic proteins in metazoa. 28659383 1 16 theme O-linked 82:89 arg1 modification 169:180 an essential and dynamic post-translational modification 125:180 an essential and dynamic post-translational modification found on hundreds of nucleocytoplasmic proteins in metazoa 125:239 O-linked N-acetylglucosamine (O-GlcNAc) is an essential and dynamic post-translational modification found on hundreds of nucleocytoplasmic proteins in metazoa. 28659383 1 16 theme O-linked 82:89 arg1 O-GlcNAc 112:119 O-GlcNAc 112:119 O-GlcNAc 112:119 O-linked N-acetylglucosamine (O-GlcNAc) is an essential and dynamic post-translational modification found on hundreds of nucleocytoplasmic proteins in metazoa. 28659383 2 17 theme entire 310:315 arg1 proteome 336:343 the entire cytosolic O-GlcNAc proteome 306:343 the entire cytosolic O-GlcNAc proteome 306:343 Although a single enzyme, O-GlcNAc transferase (OGT), generates the entire cytosolic O-GlcNAc proteome, it is not understood how it recognizes its protein substrates, targeting only a fraction of serines/threonines in the metazoan proteome for glycosylation. 28659383 0 18 theme glycosylation 17:29 arg1 substrate 31:39 a glycosylation substrate 15:39 a glycosylation substrate 15:39 Recognition of a glycosylation substrate by the O-GlcNAc transferase TPR repeats. 28659383 4 19 theme glycosylation 764:776 arg1 specificity 788:798 glycosylation substrate specificity 764:798 glycosylation substrate specificity 764:798 Confirmed by mutagenesis, this interaction suggests that glycosylation substrate specificity is achieved by recognition of a degenerate sequon in the active site combined with an extended conformation C-terminal of the O-GlcNAc target site. 28659383 4 20 theme sequon 843:848 arg1 recognition 815:825 recognition 815:825 recognition of a degenerate sequon in the active site combined with an extended conformation C-terminal of the O-GlcNAc target site 815:945 Confirmed by mutagenesis, this interaction suggests that glycosylation substrate specificity is achieved by recognition of a degenerate sequon in the active site combined with an extended conformation C-terminal of the O-GlcNAc target site. 28659383 1 21 theme nucleocytoplasmic 203:219 arg1 proteins 221:228 nucleocytoplasmic proteins 203:228 nucleocytoplasmic proteins in metazoa 203:239 O-linked N-acetylglucosamine (O-GlcNAc) is an essential and dynamic post-translational modification found on hundreds of nucleocytoplasmic proteins in metazoa. 28659383 4 22 theme site 942:945 arg1 conformation 895:906 an extended conformation C-terminal 883:917 an extended conformation C-terminal of the O-GlcNAc target site 883:945 Confirmed by mutagenesis, this interaction suggests that glycosylation substrate specificity is achieved by recognition of a degenerate sequon in the active site combined with an extended conformation C-terminal of the O-GlcNAc target site. 28659383 3 23 theme extensive 641:649 arg1 interactions 651:662 extensive interactions 641:662 extensive interactions with the tetratricopeptide repeats of OGT 641:704 We describe a trapped complex of human OGT with the C-terminal domain of TAB1, a key innate immunity-signalling O-GlcNAc protein, revealing extensive interactions with the tetratricopeptide repeats of OGT. 28659383 3 24 theme C-terminal 553:562 arg1 TAB1 574:577 TAB1 574:577 TAB1 574:577 We describe a trapped complex of human OGT with the C-terminal domain of TAB1, a key innate immunity-signalling O-GlcNAc protein, revealing extensive interactions with the tetratricopeptide repeats of OGT. 28659383 3 24 theme C-terminal 553:562 arg1 domain 564:569 the C-terminal domain 549:569 the C-terminal domain of TAB1, a key innate immunity-signalling O-GlcNAc protein 549:628 We describe a trapped complex of human OGT with the C-terminal domain of TAB1, a key innate immunity-signalling O-GlcNAc protein, revealing extensive interactions with the tetratricopeptide repeats of OGT. 28659383 1 25 theme proteins 221:228 arg1 hundreds 191:198 hundreds 191:198 hundreds of nucleocytoplasmic proteins in metazoa 191:239 O-linked N-acetylglucosamine (O-GlcNAc) is an essential and dynamic post-translational modification found on hundreds of nucleocytoplasmic proteins in metazoa. 28659383 1 26 located found 182:186 arg1 hundreds 191:198 hundreds 191:198 hundreds of nucleocytoplasmic proteins in metazoa 191:239 O-linked N-acetylglucosamine (O-GlcNAc) is an essential and dynamic post-translational modification found on hundreds of nucleocytoplasmic proteins in metazoa. 28659383 1 26 located found 182:186 arg2 modification 169:180 an essential and dynamic post-translational modification 125:180 an essential and dynamic post-translational modification found on hundreds of nucleocytoplasmic proteins in metazoa 125:239 O-linked N-acetylglucosamine (O-GlcNAc) is an essential and dynamic post-translational modification found on hundreds of nucleocytoplasmic proteins in metazoa. 28659383 1 26 located found 182:186 arg2 N-acetylglucosamine 91:109 O-linked N-acetylglucosamine 82:109 O-linked N-acetylglucosamine (O-GlcNAc) 82:120 O-linked N-acetylglucosamine (O-GlcNAc) is an essential and dynamic post-translational modification found on hundreds of nucleocytoplasmic proteins in metazoa. 28659383 2 27 theme single 253:258 arg1 enzyme 260:265 a single enzyme 251:265 a single enzyme 251:265 Although a single enzyme, O-GlcNAc transferase (OGT), generates the entire cytosolic O-GlcNAc proteome, it is not understood how it recognizes its protein substrates, targeting only a fraction of serines/threonines in the metazoan proteome for glycosylation. 28659383 2 27 theme single 253:258 arg1 transferase 277:287 O-GlcNAc transferase 268:287 O-GlcNAc transferase (OGT) 268:293 Although a single enzyme, O-GlcNAc transferase (OGT), generates the entire cytosolic O-GlcNAc proteome, it is not understood how it recognizes its protein substrates, targeting only a fraction of serines/threonines in the metazoan proteome for glycosylation. 28659383 3 28 with interactions 651:662 arg1 repeats 691:697 the tetratricopeptide repeats 669:697 the tetratricopeptide repeats of OGT 669:704 We describe a trapped complex of human OGT with the C-terminal domain of TAB1, a key innate immunity-signalling O-GlcNAc protein, revealing extensive interactions with the tetratricopeptide repeats of OGT. 28659383 2 29 theme metazoan 464:471 arg1 proteome 473:480 the metazoan proteome 460:480 the metazoan proteome 460:480 Although a single enzyme, O-GlcNAc transferase (OGT), generates the entire cytosolic O-GlcNAc proteome, it is not understood how it recognizes its protein substrates, targeting only a fraction of serines/threonines in the metazoan proteome for glycosylation. 28659383 0 30 theme substrate 31:39 arg1 Recognition 0:10 Recognition 0:10 Recognition of a glycosylation substrate by the O-GlcNAc transferase TPR repeats. 0:80 Recognition of a glycosylation substrate by the O-GlcNAc transferase TPR repeats. 28659383 3 31 theme key 582:584 arg1 TAB1 574:577 TAB1 574:577 TAB1 574:577 We describe a trapped complex of human OGT with the C-terminal domain of TAB1, a key innate immunity-signalling O-GlcNAc protein, revealing extensive interactions with the tetratricopeptide repeats of OGT. 28659383 3 31 theme key 582:584 arg1 protein 622:628 a key innate immunity-signalling O-GlcNAc protein 580:628 a key innate immunity-signalling O-GlcNAc protein 580:628 We describe a trapped complex of human OGT with the C-terminal domain of TAB1, a key innate immunity-signalling O-GlcNAc protein, revealing extensive interactions with the tetratricopeptide repeats of OGT. 28659383 0 32 theme O-GlcNAc 48:55 arg1 repeats 73:79 the O-GlcNAc transferase TPR repeats 44:79 the O-GlcNAc transferase TPR repeats 44:79 Recognition of a glycosylation substrate by the O-GlcNAc transferase TPR repeats. 28659383 3 33 theme TAB1 574:577 arg1 TAB1 574:577 TAB1 574:577 TAB1 574:577 We describe a trapped complex of human OGT with the C-terminal domain of TAB1, a key innate immunity-signalling O-GlcNAc protein, revealing extensive interactions with the tetratricopeptide repeats of OGT. 28659383 3 33 theme TAB1 574:577 arg1 domain 564:569 the C-terminal domain 549:569 the C-terminal domain of TAB1, a key innate immunity-signalling O-GlcNAc protein 549:628 We describe a trapped complex of human OGT with the C-terminal domain of TAB1, a key innate immunity-signalling O-GlcNAc protein, revealing extensive interactions with the tetratricopeptide repeats of OGT. 28659383 1 34 from metazoa 233:239 arg1 hundreds 191:198 hundreds 191:198 hundreds of nucleocytoplasmic proteins in metazoa 191:239 O-linked N-acetylglucosamine (O-GlcNAc) is an essential and dynamic post-translational modification found on hundreds of nucleocytoplasmic proteins in metazoa. 28659383 3 35 theme tetratricopeptide 673:689 arg1 repeats 691:697 the tetratricopeptide repeats 669:697 the tetratricopeptide repeats of OGT 669:704 We describe a trapped complex of human OGT with the C-terminal domain of TAB1, a key innate immunity-signalling O-GlcNAc protein, revealing extensive interactions with the tetratricopeptide repeats of OGT. 28659383 4 36 theme degenerate 832:841 arg1 sequon 843:848 a degenerate sequon 830:848 a degenerate sequon 830:848 Confirmed by mutagenesis, this interaction suggests that glycosylation substrate specificity is achieved by recognition of a degenerate sequon in the active site combined with an extended conformation C-terminal of the O-GlcNAc target site. 28659383 4 37 theme target 935:940 arg1 site 942:945 the O-GlcNAc target site 922:945 the O-GlcNAc target site 922:945 Confirmed by mutagenesis, this interaction suggests that glycosylation substrate specificity is achieved by recognition of a degenerate sequon in the active site combined with an extended conformation C-terminal of the O-GlcNAc target site. 28659383 3 38 theme O-GlcNAc 613:620 arg1 TAB1 574:577 TAB1 574:577 TAB1 574:577 We describe a trapped complex of human OGT with the C-terminal domain of TAB1, a key innate immunity-signalling O-GlcNAc protein, revealing extensive interactions with the tetratricopeptide repeats of OGT. 28659383 3 38 theme O-GlcNAc 613:620 arg1 protein 622:628 a key innate immunity-signalling O-GlcNAc protein 580:628 a key innate immunity-signalling O-GlcNAc protein 580:628 We describe a trapped complex of human OGT with the C-terminal domain of TAB1, a key innate immunity-signalling O-GlcNAc protein, revealing extensive interactions with the tetratricopeptide repeats of OGT. 28659383 1 39 from proteins 221:228 arg1 metazoa 233:239 metazoa 233:239 metazoa 233:239 O-linked N-acetylglucosamine (O-GlcNAc) is an essential and dynamic post-translational modification found on hundreds of nucleocytoplasmic proteins in metazoa. 28659383 4 40 theme O-GlcNAc 926:933 arg1 site 942:945 the O-GlcNAc target site 922:945 the O-GlcNAc target site 922:945 Confirmed by mutagenesis, this interaction suggests that glycosylation substrate specificity is achieved by recognition of a degenerate sequon in the active site combined with an extended conformation C-terminal of the O-GlcNAc target site. 28659383 2 41 theme O-GlcNAc 268:275 arg1 OGT 290:292 OGT 290:292 OGT 290:292 Although a single enzyme, O-GlcNAc transferase (OGT), generates the entire cytosolic O-GlcNAc proteome, it is not understood how it recognizes its protein substrates, targeting only a fraction of serines/threonines in the metazoan proteome for glycosylation. 28659383 2 41 theme O-GlcNAc 268:275 arg1 enzyme 260:265 a single enzyme 251:265 a single enzyme 251:265 Although a single enzyme, O-GlcNAc transferase (OGT), generates the entire cytosolic O-GlcNAc proteome, it is not understood how it recognizes its protein substrates, targeting only a fraction of serines/threonines in the metazoan proteome for glycosylation. 28659383 2 41 theme O-GlcNAc 268:275 arg1 transferase 277:287 O-GlcNAc transferase 268:287 O-GlcNAc transferase (OGT) 268:293 Although a single enzyme, O-GlcNAc transferase (OGT), generates the entire cytosolic O-GlcNAc proteome, it is not understood how it recognizes its protein substrates, targeting only a fraction of serines/threonines in the metazoan proteome for glycosylation. 28659383 1 42 from hundreds 191:198 arg1 metazoa 233:239 metazoa 233:239 metazoa 233:239 O-linked N-acetylglucosamine (O-GlcNAc) is an essential and dynamic post-translational modification found on hundreds of nucleocytoplasmic proteins in metazoa. 28659383 1 43 theme essential 128:136 arg1 N-acetylglucosamine 91:109 O-linked N-acetylglucosamine 82:109 O-linked N-acetylglucosamine (O-GlcNAc) 82:120 O-linked N-acetylglucosamine (O-GlcNAc) is an essential and dynamic post-translational modification found on hundreds of nucleocytoplasmic proteins in metazoa. 28659383 1 43 theme essential 128:136 arg1 modification 169:180 an essential and dynamic post-translational modification 125:180 an essential and dynamic post-translational modification found on hundreds of nucleocytoplasmic proteins in metazoa 125:239 O-linked N-acetylglucosamine (O-GlcNAc) is an essential and dynamic post-translational modification found on hundreds of nucleocytoplasmic proteins in metazoa. 28659383 0 44 theme TPR 69:71 arg1 repeats 73:79 the O-GlcNAc transferase TPR repeats 44:79 the O-GlcNAc transferase TPR repeats 44:79 Recognition of a glycosylation substrate by the O-GlcNAc transferase TPR repeats. 28659383 3 45 theme innate 586:591 arg1 TAB1 574:577 TAB1 574:577 TAB1 574:577 We describe a trapped complex of human OGT with the C-terminal domain of TAB1, a key innate immunity-signalling O-GlcNAc protein, revealing extensive interactions with the tetratricopeptide repeats of OGT. 28659383 3 45 theme innate 586:591 arg1 protein 622:628 a key innate immunity-signalling O-GlcNAc protein 580:628 a key innate immunity-signalling O-GlcNAc protein 580:628 We describe a trapped complex of human OGT with the C-terminal domain of TAB1, a key innate immunity-signalling O-GlcNAc protein, revealing extensive interactions with the tetratricopeptide repeats of OGT. 28659383 3 46 theme trapped 515:521 arg1 complex 523:529 a trapped complex 513:529 a trapped complex of human OGT with the C-terminal domain of TAB1, a key innate immunity-signalling O-GlcNAc protein 513:628 We describe a trapped complex of human OGT with the C-terminal domain of TAB1, a key innate immunity-signalling O-GlcNAc protein, revealing extensive interactions with the tetratricopeptide repeats of OGT. 28659383 0 47 theme transferase 57:67 arg1 repeats 73:79 the O-GlcNAc transferase TPR repeats 44:79 the O-GlcNAc transferase TPR repeats 44:79 Recognition of a glycosylation substrate by the O-GlcNAc transferase TPR repeats. 28659383 2 48 from fraction 426:433 arg1 proteome 473:480 the metazoan proteome 460:480 the metazoan proteome 460:480 Although a single enzyme, O-GlcNAc transferase (OGT), generates the entire cytosolic O-GlcNAc proteome, it is not understood how it recognizes its protein substrates, targeting only a fraction of serines/threonines in the metazoan proteome for glycosylation. 28659383 3 49 theme immunity-signalling 593:611 arg1 TAB1 574:577 TAB1 574:577 TAB1 574:577 We describe a trapped complex of human OGT with the C-terminal domain of TAB1, a key innate immunity-signalling O-GlcNAc protein, revealing extensive interactions with the tetratricopeptide repeats of OGT. 28659383 3 49 theme immunity-signalling 593:611 arg1 protein 622:628 a key innate immunity-signalling O-GlcNAc protein 580:628 a key innate immunity-signalling O-GlcNAc protein 580:628 We describe a trapped complex of human OGT with the C-terminal domain of TAB1, a key innate immunity-signalling O-GlcNAc protein, revealing extensive interactions with the tetratricopeptide repeats of OGT. 28659383 4 50 from recognition 815:825 arg1 site 864:867 the active site 853:867 the active site combined with an extended conformation C-terminal of the O-GlcNAc target site 853:945 Confirmed by mutagenesis, this interaction suggests that glycosylation substrate specificity is achieved by recognition of a degenerate sequon in the active site combined with an extended conformation C-terminal of the O-GlcNAc target site. 28659383 1 51 theme dynamic 142:148 arg1 N-acetylglucosamine 91:109 O-linked N-acetylglucosamine 82:109 O-linked N-acetylglucosamine (O-GlcNAc) 82:120 O-linked N-acetylglucosamine (O-GlcNAc) is an essential and dynamic post-translational modification found on hundreds of nucleocytoplasmic proteins in metazoa. 28659383 1 51 theme dynamic 142:148 arg1 modification 169:180 an essential and dynamic post-translational modification 125:180 an essential and dynamic post-translational modification found on hundreds of nucleocytoplasmic proteins in metazoa 125:239 O-linked N-acetylglucosamine (O-GlcNAc) is an essential and dynamic post-translational modification found on hundreds of nucleocytoplasmic proteins in metazoa. 29226084 6 0 gly N-glycosylation 1199:1213 arg1 membrane 1259:1266 cell membrane expression 1254:1277 cell membrane expression of GPR61 1254:1286 These results demonstrate that GPR61 is subject to N-glycosylation but suggest this is not a prerequisite for cell surface expression, although N-glycosylation of other proteins may be important for cell membrane expression of GPR61. 29226084 6 0 gly N-glycosylation 1199:1213 arg1 GPR61 1282:1286 GPR61 1282:1286 GPR61 1282:1286 These results demonstrate that GPR61 is subject to N-glycosylation but suggest this is not a prerequisite for cell surface expression, although N-glycosylation of other proteins may be important for cell membrane expression of GPR61. 29226084 6 0 gly N-glycosylation 1199:1213 arg1 cell 1254:1257 cell membrane expression 1254:1277 cell membrane expression of GPR61 1254:1286 These results demonstrate that GPR61 is subject to N-glycosylation but suggest this is not a prerequisite for cell surface expression, although N-glycosylation of other proteins may be important for cell membrane expression of GPR61. 29226084 6 0 gly N-glycosylation 1199:1213 arg1 proteins 1224:1231 other proteins 1218:1231 other proteins 1218:1231 These results demonstrate that GPR61 is subject to N-glycosylation but suggest this is not a prerequisite for cell surface expression, although N-glycosylation of other proteins may be important for cell membrane expression of GPR61. 29226084 2 1 theme human 297:301 arg1 cells 303:307 human cells 297:307 human cells 297:307 One of these orphan receptors is GPR61; there are little data about its expression in human cells and tissues. 29226084 8 2 theme autoimmune 1620:1629 arg1 diseases 1631:1638 autoimmune diseases 1620:1638 autoimmune diseases 1620:1638 In the latter, there was a significantly higher expression of GPR61 in the Th17 cell subset in comparison with resting CD4+ cells, which may point toward a potential role for the GPR61 receptor in autoimmune diseases. 29226084 4 3 theme N-glycosylation 814:828 arg1 site 830:833 disrupted consensus N-glycosylation site 794:833 disrupted consensus N-glycosylation site 794:833 The N-glycosylation inhibitor tunicamycin reduced the apparent molecular weight of immunoreactivity associated with myc-tagged GPR61 by 1-2 kDa, which was comparable to the evident molecular weight of the myc-tagged N12S GPR61 mutant with disrupted consensus N-glycosylation site. 29226084 2 4 from expression 283:292 arg1 cells 303:307 human cells 297:307 human cells 297:307 One of these orphan receptors is GPR61; there are little data about its expression in human cells and tissues. 29226084 2 4 from expression 283:292 arg1 tissues 313:319 tissues 313:319 tissues 313:319 One of these orphan receptors is GPR61; there are little data about its expression in human cells and tissues. 29226084 6 5 theme surface 1170:1176 arg1 expression 1178:1187 cell surface expression 1165:1187 cell surface expression 1165:1187 These results demonstrate that GPR61 is subject to N-glycosylation but suggest this is not a prerequisite for cell surface expression, although N-glycosylation of other proteins may be important for cell membrane expression of GPR61. 29226084 6 6 theme membrane 1259:1266 arg1 expression 1268:1277 cell membrane expression 1254:1277 cell membrane expression of GPR61 1254:1286 These results demonstrate that GPR61 is subject to N-glycosylation but suggest this is not a prerequisite for cell surface expression, although N-glycosylation of other proteins may be important for cell membrane expression of GPR61. 29226084 2 7 theme receptors 231:239 arg1 receptors 231:239 these orphan receptors 218:239 these orphan receptors 218:239 One of these orphan receptors is GPR61; there are little data about its expression in human cells and tissues. 29226084 2 7 theme receptors 231:239 arg1 One 211:213 One 211:213 One 211:213 One of these orphan receptors is GPR61; there are little data about its expression in human cells and tissues. 29226084 1 8 theme receptors 154:162 arg1 class 132:136 the G protein-coupled receptor class 101:136 the G protein-coupled receptor class of cell surface receptors 101:162 A number of members of the G protein-coupled receptor class of cell surface receptors are 'orphans' with no known endogenous ligand. 29226084 4 9 theme immunoreactivity 638:653 arg1 weight 628:633 the apparent molecular weight 605:633 the apparent molecular weight of immunoreactivity associated with myc-tagged GPR61 by 1-2 kDa, which was comparable to the evident molecular weight of the myc-tagged N12S GPR61 mutant with disrupted consensus N-glycosylation site 605:833 The N-glycosylation inhibitor tunicamycin reduced the apparent molecular weight of immunoreactivity associated with myc-tagged GPR61 by 1-2 kDa, which was comparable to the evident molecular weight of the myc-tagged N12S GPR61 mutant with disrupted consensus N-glycosylation site. 29226084 2 10 theme little 261:266 arg1 data 268:271 little data 261:271 little data about its expression in human cells and tissues 261:319 One of these orphan receptors is GPR61; there are little data about its expression in human cells and tissues. 29226084 5 11 theme expression 854:863 arg1 Analysis 836:843 Analysis 836:843 Analysis of GPR61 expression 836:863 Analysis of GPR61 expression demonstrated that tunicamycin treatment reduced considerably heterologous expression of GPR61 in the cell membrane despite the N12S GPR61 mutant being readily expressed at the cell surface. 29226084 9 12 theme GPR61 1671:1675 arg1 protein 1677:1683 GPR61 protein 1671:1683 GPR61 protein 1671:1683 This is the first report that GPR61 protein is subject to post-translational modification and is expressed in immune cell subsets and the hippocampus. 29226084 6 13 theme proteins 1224:1231 arg1 N-glycosylation 1199:1213 N-glycosylation 1199:1213 N-glycosylation of other proteins 1199:1231 These results demonstrate that GPR61 is subject to N-glycosylation but suggest this is not a prerequisite for cell surface expression, although N-glycosylation of other proteins may be important for cell membrane expression of GPR61. 29226084 7 14 theme mononuclear 1404:1414 arg1 cells 1416:1420 human peripheral blood mononuclear cells 1381:1420 human peripheral blood mononuclear cells 1381:1420 Expression of GPR61 protein was demonstrated at the cellular level in human hippocampus and human peripheral blood mononuclear cells. 29226084 4 15 gly N-glycosylation 814:828 arg2 site 830:833 disrupted consensus N-glycosylation site 794:833 disrupted consensus N-glycosylation site 794:833 The N-glycosylation inhibitor tunicamycin reduced the apparent molecular weight of immunoreactivity associated with myc-tagged GPR61 by 1-2 kDa, which was comparable to the evident molecular weight of the myc-tagged N12S GPR61 mutant with disrupted consensus N-glycosylation site. 29226084 7 16 theme peripheral 1387:1396 arg1 cells 1416:1420 human peripheral blood mononuclear cells 1381:1420 human peripheral blood mononuclear cells 1381:1420 Expression of GPR61 protein was demonstrated at the cellular level in human hippocampus and human peripheral blood mononuclear cells. 29226084 4 17 theme apparent 609:616 arg1 weight 628:633 the apparent molecular weight 605:633 the apparent molecular weight of immunoreactivity associated with myc-tagged GPR61 by 1-2 kDa, which was comparable to the evident molecular weight of the myc-tagged N12S GPR61 mutant with disrupted consensus N-glycosylation site 605:833 The N-glycosylation inhibitor tunicamycin reduced the apparent molecular weight of immunoreactivity associated with myc-tagged GPR61 by 1-2 kDa, which was comparable to the evident molecular weight of the myc-tagged N12S GPR61 mutant with disrupted consensus N-glycosylation site. 29226084 3 18 theme protein 546:552 arg1 expression 528:537 the subcellular expression 512:537 the subcellular expression of the protein 512:552 In this study, we investigated the post-translational modification of GPR61 by N-glycosylation at an identified consensus N-glycosylation site (N12) and the impact of this modification upon the subcellular expression of the protein. 29226084 5 19 theme cell 1041:1044 arg1 surface 1046:1052 the cell surface 1037:1052 the cell surface 1037:1052 Analysis of GPR61 expression demonstrated that tunicamycin treatment reduced considerably heterologous expression of GPR61 in the cell membrane despite the N12S GPR61 mutant being readily expressed at the cell surface. 29226084 7 20 theme human 1359:1363 arg1 hippocampus 1365:1375 human hippocampus 1359:1375 human hippocampus 1359:1375 Expression of GPR61 protein was demonstrated at the cellular level in human hippocampus and human peripheral blood mononuclear cells. 29226084 6 21 theme other 1218:1222 arg1 proteins 1224:1231 other proteins 1218:1231 other proteins 1218:1231 These results demonstrate that GPR61 is subject to N-glycosylation but suggest this is not a prerequisite for cell surface expression, although N-glycosylation of other proteins may be important for cell membrane expression of GPR61. 29226084 10 22 theme guide 1817:1821 arg1 studies 1823:1829 guide studies 1817:1829 guide studies 1817:1829 These findings will help guide studies to investigate the function of GPR61. 29226084 1 23 theme protein-coupled 107:121 arg1 class 132:136 the G protein-coupled receptor class 101:136 the G protein-coupled receptor class of cell surface receptors 101:162 A number of members of the G protein-coupled receptor class of cell surface receptors are 'orphans' with no known endogenous ligand. 29226084 8 24 theme GPR61 1485:1489 arg1 expression 1471:1480 a significantly higher expression 1448:1480 a significantly higher expression of GPR61 in the Th17 cell subset 1448:1513 In the latter, there was a significantly higher expression of GPR61 in the Th17 cell subset in comparison with resting CD4+ cells, which may point toward a potential role for the GPR61 receptor in autoimmune diseases. 29226084 4 25 with mutant 782:787 arg1 site 830:833 disrupted consensus N-glycosylation site 794:833 disrupted consensus N-glycosylation site 794:833 The N-glycosylation inhibitor tunicamycin reduced the apparent molecular weight of immunoreactivity associated with myc-tagged GPR61 by 1-2 kDa, which was comparable to the evident molecular weight of the myc-tagged N12S GPR61 mutant with disrupted consensus N-glycosylation site. 29226084 0 26 theme orphan 55:60 arg1 receptor 68:75 the orphan GPR61 receptor 51:75 the orphan GPR61 receptor 51:75 N-glycosylation and expression in human tissues of the orphan GPR61 receptor. 29226084 1 27 theme class 132:136 arg1 members 90:96 members 90:96 members of the G protein-coupled receptor class of cell surface receptors 90:162 A number of members of the G protein-coupled receptor class of cell surface receptors are 'orphans' with no known endogenous ligand. 29226084 0 28 from expression 20:29 arg1 tissues 40:46 human tissues 34:46 human tissues of the orphan GPR61 receptor 34:75 N-glycosylation and expression in human tissues of the orphan GPR61 receptor. 29226084 0 29 theme receptor 68:75 arg1 tissues 40:46 human tissues 34:46 human tissues of the orphan GPR61 receptor 34:75 N-glycosylation and expression in human tissues of the orphan GPR61 receptor. 29226084 1 30 theme cell 141:144 arg1 receptors 154:162 cell surface receptors 141:162 cell surface receptors 141:162 A number of members of the G protein-coupled receptor class of cell surface receptors are 'orphans' with no known endogenous ligand. 29226084 9 31 theme cell 1758:1761 arg1 subsets 1763:1769 immune cell subsets 1751:1769 immune cell subsets 1751:1769 This is the first report that GPR61 protein is subject to post-translational modification and is expressed in immune cell subsets and the hippocampus. 29226084 0 32 from N-glycosylation 0:14 arg1 tissues 40:46 human tissues 34:46 human tissues of the orphan GPR61 receptor 34:75 N-glycosylation and expression in human tissues of the orphan GPR61 receptor. 29226084 4 33 theme evident 728:734 arg1 weight 746:751 the evident molecular weight 724:751 the evident molecular weight of the myc-tagged N12S GPR61 mutant with disrupted consensus N-glycosylation site 724:833 The N-glycosylation inhibitor tunicamycin reduced the apparent molecular weight of immunoreactivity associated with myc-tagged GPR61 by 1-2 kDa, which was comparable to the evident molecular weight of the myc-tagged N12S GPR61 mutant with disrupted consensus N-glycosylation site. 29226084 7 34 from level 1350:1354 arg1 hippocampus 1365:1375 human hippocampus 1359:1375 human hippocampus 1359:1375 Expression of GPR61 protein was demonstrated at the cellular level in human hippocampus and human peripheral blood mononuclear cells. 29226084 7 34 from level 1350:1354 arg1 cells 1416:1420 human peripheral blood mononuclear cells 1381:1420 human peripheral blood mononuclear cells 1381:1420 Expression of GPR61 protein was demonstrated at the cellular level in human hippocampus and human peripheral blood mononuclear cells. 29226084 8 35 from expression 1471:1480 arg1 subset 1508:1513 the Th17 cell subset 1494:1513 the Th17 cell subset 1494:1513 In the latter, there was a significantly higher expression of GPR61 in the Th17 cell subset in comparison with resting CD4+ cells, which may point toward a potential role for the GPR61 receptor in autoimmune diseases. 29226084 7 36 theme cellular 1341:1348 arg1 level 1350:1354 the cellular level 1337:1354 the cellular level in human hippocampus and human peripheral blood mononuclear cells 1337:1420 Expression of GPR61 protein was demonstrated at the cellular level in human hippocampus and human peripheral blood mononuclear cells. 29226084 3 37 theme post-translational 357:374 arg1 modification 376:387 the post-translational modification 353:387 the post-translational modification of GPR61 by N-glycosylation at an identified consensus N-glycosylation site (N12) 353:469 In this study, we investigated the post-translational modification of GPR61 by N-glycosylation at an identified consensus N-glycosylation site (N12) and the impact of this modification upon the subcellular expression of the protein. 29226084 5 38 theme GPR61 953:957 arg1 expression 939:948 considerably heterologous expression 913:948 considerably heterologous expression of GPR61 in the cell membrane 913:978 Analysis of GPR61 expression demonstrated that tunicamycin treatment reduced considerably heterologous expression of GPR61 in the cell membrane despite the N12S GPR61 mutant being readily expressed at the cell surface. 29226084 8 39 theme CD4+ 1542:1545 arg1 cells 1547:1551 resting CD4+ cells 1534:1551 resting CD4+ cells 1534:1551 In the latter, there was a significantly higher expression of GPR61 in the Th17 cell subset in comparison with resting CD4+ cells, which may point toward a potential role for the GPR61 receptor in autoimmune diseases. 29226084 1 40 theme members 90:96 arg1 number 80:85 A number 78:85 A number of members of the G protein-coupled receptor class of cell surface receptors 78:162 A number of members of the G protein-coupled receptor class of cell surface receptors are 'orphans' with no known endogenous ligand. 29226084 1 40 theme members 90:96 arg1 orphans 169:175 'orphans' 168:176 'orphans' with no known endogenous ligand 168:208 A number of members of the G protein-coupled receptor class of cell surface receptors are 'orphans' with no known endogenous ligand. 29226084 4 41 theme mutant 782:787 arg1 weight 746:751 the evident molecular weight 724:751 the evident molecular weight of the myc-tagged N12S GPR61 mutant with disrupted consensus N-glycosylation site 724:833 The N-glycosylation inhibitor tunicamycin reduced the apparent molecular weight of immunoreactivity associated with myc-tagged GPR61 by 1-2 kDa, which was comparable to the evident molecular weight of the myc-tagged N12S GPR61 mutant with disrupted consensus N-glycosylation site. 29226084 8 42 with comparison 1518:1527 arg1 cells 1547:1551 resting CD4+ cells 1534:1551 resting CD4+ cells 1534:1551 In the latter, there was a significantly higher expression of GPR61 in the Th17 cell subset in comparison with resting CD4+ cells, which may point toward a potential role for the GPR61 receptor in autoimmune diseases. 29226084 0 43 theme human 34:38 arg1 tissues 40:46 human tissues 34:46 human tissues of the orphan GPR61 receptor 34:75 N-glycosylation and expression in human tissues of the orphan GPR61 receptor. 29226084 7 44 theme GPR61 1303:1307 arg1 protein 1309:1315 GPR61 protein 1303:1315 GPR61 protein 1303:1315 Expression of GPR61 protein was demonstrated at the cellular level in human hippocampus and human peripheral blood mononuclear cells. 29226084 4 45 theme disrupted 794:802 arg1 site 830:833 disrupted consensus N-glycosylation site 794:833 disrupted consensus N-glycosylation site 794:833 The N-glycosylation inhibitor tunicamycin reduced the apparent molecular weight of immunoreactivity associated with myc-tagged GPR61 by 1-2 kDa, which was comparable to the evident molecular weight of the myc-tagged N12S GPR61 mutant with disrupted consensus N-glycosylation site. 29226084 3 46 theme N-glycosylation 444:458 arg1 N12 466:468 N12 466:468 N12 466:468 In this study, we investigated the post-translational modification of GPR61 by N-glycosylation at an identified consensus N-glycosylation site (N12) and the impact of this modification upon the subcellular expression of the protein. 29226084 3 46 theme N-glycosylation 444:458 arg1 site 460:463 an identified consensus N-glycosylation site 420:463 an identified consensus N-glycosylation site (N12) 420:469 In this study, we investigated the post-translational modification of GPR61 by N-glycosylation at an identified consensus N-glycosylation site (N12) and the impact of this modification upon the subcellular expression of the protein. 29226084 9 47 theme first 1653:1657 arg1 This 1641:1644 This 1641:1644 This 1641:1644 This is the first report that GPR61 protein is subject to post-translational modification and is expressed in immune cell subsets and the hippocampus. 29226084 9 47 theme first 1653:1657 arg1 report 1659:1664 the first report 1649:1664 the first report that GPR61 protein is subject to post-translational modification and is expressed in immune cell subsets and the hippocampus 1649:1789 This is the first report that GPR61 protein is subject to post-translational modification and is expressed in immune cell subsets and the hippocampus. 29226084 3 48 theme identified 423:432 arg1 N12 466:468 N12 466:468 N12 466:468 In this study, we investigated the post-translational modification of GPR61 by N-glycosylation at an identified consensus N-glycosylation site (N12) and the impact of this modification upon the subcellular expression of the protein. 29226084 3 48 theme identified 423:432 arg1 site 460:463 an identified consensus N-glycosylation site 420:463 an identified consensus N-glycosylation site (N12) 420:469 In this study, we investigated the post-translational modification of GPR61 by N-glycosylation at an identified consensus N-glycosylation site (N12) and the impact of this modification upon the subcellular expression of the protein. 29226084 1 49 theme known 186:190 arg1 ligand 203:208 no known endogenous ligand 183:208 no known endogenous ligand 183:208 A number of members of the G protein-coupled receptor class of cell surface receptors are 'orphans' with no known endogenous ligand. 29226084 8 50 theme potential 1579:1587 arg1 role 1589:1592 a potential role 1577:1592 a potential role for the GPR61 receptor in autoimmune diseases 1577:1638 In the latter, there was a significantly higher expression of GPR61 in the Th17 cell subset in comparison with resting CD4+ cells, which may point toward a potential role for the GPR61 receptor in autoimmune diseases. 29226084 4 51 theme N12S 771:774 arg1 mutant 782:787 the myc-tagged N12S GPR61 mutant 756:787 the myc-tagged N12S GPR61 mutant with disrupted consensus N-glycosylation site 756:833 The N-glycosylation inhibitor tunicamycin reduced the apparent molecular weight of immunoreactivity associated with myc-tagged GPR61 by 1-2 kDa, which was comparable to the evident molecular weight of the myc-tagged N12S GPR61 mutant with disrupted consensus N-glycosylation site. 29226084 4 52 theme N-glycosylation 559:573 arg1 tunicamycin 585:595 The N-glycosylation inhibitor tunicamycin 555:595 The N-glycosylation inhibitor tunicamycin 555:595 The N-glycosylation inhibitor tunicamycin reduced the apparent molecular weight of immunoreactivity associated with myc-tagged GPR61 by 1-2 kDa, which was comparable to the evident molecular weight of the myc-tagged N12S GPR61 mutant with disrupted consensus N-glycosylation site. 29226084 8 53 theme GPR61 1602:1606 arg1 receptor 1608:1615 the GPR61 receptor 1598:1615 the GPR61 receptor 1598:1615 In the latter, there was a significantly higher expression of GPR61 in the Th17 cell subset in comparison with resting CD4+ cells, which may point toward a potential role for the GPR61 receptor in autoimmune diseases. 29226084 6 54 theme GPR61 1282:1286 arg1 expression 1268:1277 cell membrane expression 1254:1277 cell membrane expression of GPR61 1254:1286 These results demonstrate that GPR61 is subject to N-glycosylation but suggest this is not a prerequisite for cell surface expression, although N-glycosylation of other proteins may be important for cell membrane expression of GPR61. 29226084 3 55 gly N-glycosylation 401:415 arg1 N12 466:468 N12 466:468 N12 466:468 In this study, we investigated the post-translational modification of GPR61 by N-glycosylation at an identified consensus N-glycosylation site (N12) and the impact of this modification upon the subcellular expression of the protein. 29226084 3 55 gly N-glycosylation 401:415 arg2 N12 466:468 N12 466:468 N12 466:468 In this study, we investigated the post-translational modification of GPR61 by N-glycosylation at an identified consensus N-glycosylation site (N12) and the impact of this modification upon the subcellular expression of the protein. 29226084 3 55 gly N-glycosylation 401:415 arg1 site 460:463 an identified consensus N-glycosylation site 420:463 an identified consensus N-glycosylation site (N12) 420:469 In this study, we investigated the post-translational modification of GPR61 by N-glycosylation at an identified consensus N-glycosylation site (N12) and the impact of this modification upon the subcellular expression of the protein. 29226084 3 55 gly N-glycosylation 401:415 arg2 site 460:463 an identified consensus N-glycosylation site 420:463 an identified consensus N-glycosylation site (N12) 420:469 In this study, we investigated the post-translational modification of GPR61 by N-glycosylation at an identified consensus N-glycosylation site (N12) and the impact of this modification upon the subcellular expression of the protein. 29226084 1 56 theme surface 146:152 arg1 receptors 154:162 cell surface receptors 141:162 cell surface receptors 141:162 A number of members of the G protein-coupled receptor class of cell surface receptors are 'orphans' with no known endogenous ligand. 29226084 4 57 theme consensus 804:812 arg1 site 830:833 disrupted consensus N-glycosylation site 794:833 disrupted consensus N-glycosylation site 794:833 The N-glycosylation inhibitor tunicamycin reduced the apparent molecular weight of immunoreactivity associated with myc-tagged GPR61 by 1-2 kDa, which was comparable to the evident molecular weight of the myc-tagged N12S GPR61 mutant with disrupted consensus N-glycosylation site. 29226084 6 58 theme cell 1165:1168 arg1 expression 1178:1187 cell surface expression 1165:1187 cell surface expression 1165:1187 These results demonstrate that GPR61 is subject to N-glycosylation but suggest this is not a prerequisite for cell surface expression, although N-glycosylation of other proteins may be important for cell membrane expression of GPR61. 29226084 4 59 theme molecular 618:626 arg1 weight 628:633 the apparent molecular weight 605:633 the apparent molecular weight of immunoreactivity associated with myc-tagged GPR61 by 1-2 kDa, which was comparable to the evident molecular weight of the myc-tagged N12S GPR61 mutant with disrupted consensus N-glycosylation site 605:833 The N-glycosylation inhibitor tunicamycin reduced the apparent molecular weight of immunoreactivity associated with myc-tagged GPR61 by 1-2 kDa, which was comparable to the evident molecular weight of the myc-tagged N12S GPR61 mutant with disrupted consensus N-glycosylation site. 29226084 6 60 theme cell 1254:1257 arg1 expression 1268:1277 cell membrane expression 1254:1277 cell membrane expression of GPR61 1254:1286 These results demonstrate that GPR61 is subject to N-glycosylation but suggest this is not a prerequisite for cell surface expression, although N-glycosylation of other proteins may be important for cell membrane expression of GPR61. 29226084 5 61 theme GPR61 848:852 arg1 expression 854:863 GPR61 expression 848:863 GPR61 expression 848:863 Analysis of GPR61 expression demonstrated that tunicamycin treatment reduced considerably heterologous expression of GPR61 in the cell membrane despite the N12S GPR61 mutant being readily expressed at the cell surface. 29226084 3 62 from site 460:463 arg1 N-glycosylation 401:415 N-glycosylation 401:415 N-glycosylation at an identified consensus N-glycosylation site (N12) 401:469 In this study, we investigated the post-translational modification of GPR61 by N-glycosylation at an identified consensus N-glycosylation site (N12) and the impact of this modification upon the subcellular expression of the protein. 29226084 3 63 theme modification 494:505 arg1 modification 376:387 the post-translational modification 353:387 the post-translational modification of GPR61 by N-glycosylation at an identified consensus N-glycosylation site (N12) 353:469 In this study, we investigated the post-translational modification of GPR61 by N-glycosylation at an identified consensus N-glycosylation site (N12) and the impact of this modification upon the subcellular expression of the protein. 29226084 3 63 theme modification 494:505 arg1 impact 479:484 the impact 475:484 the impact of this modification upon the subcellular expression of the protein 475:552 In this study, we investigated the post-translational modification of GPR61 by N-glycosylation at an identified consensus N-glycosylation site (N12) and the impact of this modification upon the subcellular expression of the protein. 29226084 3 64 theme subcellular 516:526 arg1 expression 528:537 the subcellular expression 512:537 the subcellular expression of the protein 512:552 In this study, we investigated the post-translational modification of GPR61 by N-glycosylation at an identified consensus N-glycosylation site (N12) and the impact of this modification upon the subcellular expression of the protein. 29226084 8 65 from role 1589:1592 arg1 diseases 1631:1638 autoimmune diseases 1620:1638 autoimmune diseases 1620:1638 In the latter, there was a significantly higher expression of GPR61 in the Th17 cell subset in comparison with resting CD4+ cells, which may point toward a potential role for the GPR61 receptor in autoimmune diseases. 29226084 8 66 theme higher 1464:1469 arg1 expression 1471:1480 a significantly higher expression 1448:1480 a significantly higher expression of GPR61 in the Th17 cell subset 1448:1513 In the latter, there was a significantly higher expression of GPR61 in the Th17 cell subset in comparison with resting CD4+ cells, which may point toward a potential role for the GPR61 receptor in autoimmune diseases. 29226084 7 67 theme blood 1398:1402 arg1 cells 1416:1420 human peripheral blood mononuclear cells 1381:1420 human peripheral blood mononuclear cells 1381:1420 Expression of GPR61 protein was demonstrated at the cellular level in human hippocampus and human peripheral blood mononuclear cells. 29226084 8 68 theme cell 1503:1506 arg1 subset 1508:1513 the Th17 cell subset 1494:1513 the Th17 cell subset 1494:1513 In the latter, there was a significantly higher expression of GPR61 in the Th17 cell subset in comparison with resting CD4+ cells, which may point toward a potential role for the GPR61 receptor in autoimmune diseases. 29226084 9 69 theme post-translational 1699:1716 arg1 modification 1718:1729 post-translational modification 1699:1729 post-translational modification 1699:1729 This is the first report that GPR61 protein is subject to post-translational modification and is expressed in immune cell subsets and the hippocampus. 29226084 7 70 theme human 1381:1385 arg1 cells 1416:1420 human peripheral blood mononuclear cells 1381:1420 human peripheral blood mononuclear cells 1381:1420 Expression of GPR61 protein was demonstrated at the cellular level in human hippocampus and human peripheral blood mononuclear cells. 29226084 2 71 theme orphan 224:229 arg1 receptors 231:239 these orphan receptors 218:239 these orphan receptors 218:239 One of these orphan receptors is GPR61; there are little data about its expression in human cells and tissues. 29226084 5 72 theme heterologous 926:937 arg1 expression 939:948 considerably heterologous expression 913:948 considerably heterologous expression of GPR61 in the cell membrane 913:978 Analysis of GPR61 expression demonstrated that tunicamycin treatment reduced considerably heterologous expression of GPR61 in the cell membrane despite the N12S GPR61 mutant being readily expressed at the cell surface. 29226084 0 73 theme GPR61 62:66 arg1 receptor 68:75 the orphan GPR61 receptor 51:75 the orphan GPR61 receptor 51:75 N-glycosylation and expression in human tissues of the orphan GPR61 receptor. 29226084 1 74 theme receptor 123:130 arg1 class 132:136 the G protein-coupled receptor class 101:136 the G protein-coupled receptor class of cell surface receptors 101:162 A number of members of the G protein-coupled receptor class of cell surface receptors are 'orphans' with no known endogenous ligand. 29226084 8 75 theme Th17 1498:1501 arg1 subset 1508:1513 the Th17 cell subset 1494:1513 the Th17 cell subset 1494:1513 In the latter, there was a significantly higher expression of GPR61 in the Th17 cell subset in comparison with resting CD4+ cells, which may point toward a potential role for the GPR61 receptor in autoimmune diseases. 29226084 5 76 theme tunicamycin 883:893 arg1 treatment 895:903 tunicamycin treatment 883:903 tunicamycin treatment 883:903 Analysis of GPR61 expression demonstrated that tunicamycin treatment reduced considerably heterologous expression of GPR61 in the cell membrane despite the N12S GPR61 mutant being readily expressed at the cell surface. 29226084 9 77 theme immune 1751:1756 arg1 subsets 1763:1769 immune cell subsets 1751:1769 immune cell subsets 1751:1769 This is the first report that GPR61 protein is subject to post-translational modification and is expressed in immune cell subsets and the hippocampus. 29226084 4 78 theme myc-tagged 671:680 arg1 GPR61 682:686 myc-tagged GPR61 671:686 myc-tagged GPR61 671:686 The N-glycosylation inhibitor tunicamycin reduced the apparent molecular weight of immunoreactivity associated with myc-tagged GPR61 by 1-2 kDa, which was comparable to the evident molecular weight of the myc-tagged N12S GPR61 mutant with disrupted consensus N-glycosylation site. 29226084 5 79 theme cell 966:969 arg1 membrane 971:978 the cell membrane 962:978 the cell membrane 962:978 Analysis of GPR61 expression demonstrated that tunicamycin treatment reduced considerably heterologous expression of GPR61 in the cell membrane despite the N12S GPR61 mutant being readily expressed at the cell surface. 29226084 8 80 theme resting 1534:1540 arg1 cells 1547:1551 resting CD4+ cells 1534:1551 resting CD4+ cells 1534:1551 In the latter, there was a significantly higher expression of GPR61 in the Th17 cell subset in comparison with resting CD4+ cells, which may point toward a potential role for the GPR61 receptor in autoimmune diseases. 29226084 4 81 theme molecular 736:744 arg1 weight 746:751 the evident molecular weight 724:751 the evident molecular weight of the myc-tagged N12S GPR61 mutant with disrupted consensus N-glycosylation site 724:833 The N-glycosylation inhibitor tunicamycin reduced the apparent molecular weight of immunoreactivity associated with myc-tagged GPR61 by 1-2 kDa, which was comparable to the evident molecular weight of the myc-tagged N12S GPR61 mutant with disrupted consensus N-glycosylation site. 29226084 3 82 theme GPR61 392:396 arg1 modification 376:387 the post-translational modification 353:387 the post-translational modification of GPR61 by N-glycosylation at an identified consensus N-glycosylation site (N12) 353:469 In this study, we investigated the post-translational modification of GPR61 by N-glycosylation at an identified consensus N-glycosylation site (N12) and the impact of this modification upon the subcellular expression of the protein. 29226084 3 82 theme GPR61 392:396 arg1 impact 479:484 the impact 475:484 the impact of this modification upon the subcellular expression of the protein 475:552 In this study, we investigated the post-translational modification of GPR61 by N-glycosylation at an identified consensus N-glycosylation site (N12) and the impact of this modification upon the subcellular expression of the protein. 29226084 5 83 from expression 939:948 arg1 membrane 971:978 the cell membrane 962:978 the cell membrane 962:978 Analysis of GPR61 expression demonstrated that tunicamycin treatment reduced considerably heterologous expression of GPR61 in the cell membrane despite the N12S GPR61 mutant being readily expressed at the cell surface. 29226084 3 84 gly N-glycosylation 444:458 arg2 N12 466:468 N12 466:468 N12 466:468 In this study, we investigated the post-translational modification of GPR61 by N-glycosylation at an identified consensus N-glycosylation site (N12) and the impact of this modification upon the subcellular expression of the protein. 29226084 3 84 gly N-glycosylation 444:458 arg2 site 460:463 an identified consensus N-glycosylation site 420:463 an identified consensus N-glycosylation site (N12) 420:469 In this study, we investigated the post-translational modification of GPR61 by N-glycosylation at an identified consensus N-glycosylation site (N12) and the impact of this modification upon the subcellular expression of the protein. 29226084 7 85 theme protein 1309:1315 arg1 Expression 1289:1298 Expression 1289:1298 Expression of GPR61 protein 1289:1315 Expression of GPR61 protein was demonstrated at the cellular level in human hippocampus and human peripheral blood mononuclear cells. 29226084 9 86 dep report 1659:1664 arg1 subject 1688:1694 subject 1688:1694 subject 1688:1694 This is the first report that GPR61 protein is subject to post-translational modification and is expressed in immune cell subsets and the hippocampus. 29226084 9 86 dep report 1659:1664 arg1 expressed 1738:1746 expressed 1738:1746 is expressed in immune cell subsets and the hippocampus 1735:1789 This is the first report that GPR61 protein is subject to post-translational modification and is expressed in immune cell subsets and the hippocampus. 29226084 1 87 with orphans 169:175 arg1 ligand 203:208 no known endogenous ligand 183:208 no known endogenous ligand 183:208 A number of members of the G protein-coupled receptor class of cell surface receptors are 'orphans' with no known endogenous ligand. 29226084 0 88 gly N-glycosylation 0:14 arg1 tissues 40:46 human tissues 34:46 human tissues of the orphan GPR61 receptor 34:75 N-glycosylation and expression in human tissues of the orphan GPR61 receptor. 29226084 4 89 theme GPR61 776:780 arg1 mutant 782:787 the myc-tagged N12S GPR61 mutant 756:787 the myc-tagged N12S GPR61 mutant with disrupted consensus N-glycosylation site 756:833 The N-glycosylation inhibitor tunicamycin reduced the apparent molecular weight of immunoreactivity associated with myc-tagged GPR61 by 1-2 kDa, which was comparable to the evident molecular weight of the myc-tagged N12S GPR61 mutant with disrupted consensus N-glycosylation site. 29226084 8 90 dep was 1444:1446 arg1 point 1564:1568 point 1564:1568 may point toward a potential role for the GPR61 receptor in autoimmune diseases 1560:1638 In the latter, there was a significantly higher expression of GPR61 in the Th17 cell subset in comparison with resting CD4+ cells, which may point toward a potential role for the GPR61 receptor in autoimmune diseases. 29226084 5 91 theme N12S 992:995 arg1 mutant 1003:1008 the N12S GPR61 mutant 988:1008 the N12S GPR61 mutant 988:1008 Analysis of GPR61 expression demonstrated that tunicamycin treatment reduced considerably heterologous expression of GPR61 in the cell membrane despite the N12S GPR61 mutant being readily expressed at the cell surface. 29226084 10 92 theme GPR61 1862:1866 arg1 function 1850:1857 the function 1846:1857 the function of GPR61 1846:1866 These findings will help guide studies to investigate the function of GPR61. 29226084 3 93 theme consensus 434:442 arg1 N12 466:468 N12 466:468 N12 466:468 In this study, we investigated the post-translational modification of GPR61 by N-glycosylation at an identified consensus N-glycosylation site (N12) and the impact of this modification upon the subcellular expression of the protein. 29226084 3 93 theme consensus 434:442 arg1 site 460:463 an identified consensus N-glycosylation site 420:463 an identified consensus N-glycosylation site (N12) 420:469 In this study, we investigated the post-translational modification of GPR61 by N-glycosylation at an identified consensus N-glycosylation site (N12) and the impact of this modification upon the subcellular expression of the protein. 29226084 1 94 theme endogenous 192:201 arg1 ligand 203:208 no known endogenous ligand 183:208 no known endogenous ligand 183:208 A number of members of the G protein-coupled receptor class of cell surface receptors are 'orphans' with no known endogenous ligand. 29226084 4 95 theme inhibitor 575:583 arg1 tunicamycin 585:595 The N-glycosylation inhibitor tunicamycin 555:595 The N-glycosylation inhibitor tunicamycin 555:595 The N-glycosylation inhibitor tunicamycin reduced the apparent molecular weight of immunoreactivity associated with myc-tagged GPR61 by 1-2 kDa, which was comparable to the evident molecular weight of the myc-tagged N12S GPR61 mutant with disrupted consensus N-glycosylation site. 29226084 4 96 theme myc-tagged 760:769 arg1 mutant 782:787 the myc-tagged N12S GPR61 mutant 756:787 the myc-tagged N12S GPR61 mutant with disrupted consensus N-glycosylation site 756:833 The N-glycosylation inhibitor tunicamycin reduced the apparent molecular weight of immunoreactivity associated with myc-tagged GPR61 by 1-2 kDa, which was comparable to the evident molecular weight of the myc-tagged N12S GPR61 mutant with disrupted consensus N-glycosylation site. 28125599 2 0 gly glycosylated 279:290 arg1 NTCP 271:274 NTCP 271:274 NTCP 271:274 NTCP is glycosylated and the role of glycans in protein trafficking or viral receptor activity is not known. 28125599 7 1 theme similar 1137:1143 arg1 fashion 1145:1151 a similar fashion 1135:1151 a similar fashion 1135:1151 This affected the physiological bile acid transporter function of NTCP-N5,11Q in a similar fashion. 28125599 6 2 theme HBV 970:972 arg1 infection 974:982 HBV infection 970:982 HBV infection 970:982 However, glycosylation-deficient NTCP (NTCP-N5,11Q) failed to support HBV infection, showed minimal cellular expression and was degraded in the lysosome. 28125599 3 3 dep glycan 532:537 arg1 NTCP-N5Q 540:547 NTCP-N5Q 540:547 NTCP-N5Q 540:547 NTCP contains two N-linked glycosylation sites and asparagine amino acid residues N5 and N11 were mutated to a glutamine to generate NTCP with a single glycan (NTCP-N5Q or NTCP- N11Q) or no glycans (NTCP- N5,11Q). 28125599 3 3 dep glycan 532:537 arg1 N11Q 558:561 NTCP- N11Q 552:561 NTCP- N11Q 552:561 NTCP contains two N-linked glycosylation sites and asparagine amino acid residues N5 and N11 were mutated to a glutamine to generate NTCP with a single glycan (NTCP-N5Q or NTCP- N11Q) or no glycans (NTCP- N5,11Q). 28125599 1 4 theme B 256:256 arg1 virus 258:262 hepatitis B virus 246:262 hepatitis B virus (HBV) 246:268 The sodium/bile acid cotransporter NTCP was recently identified as a receptor for hepatitis B virus (HBV). 28125599 1 4 theme B 256:256 arg1 HBV 265:267 HBV 265:267 HBV 265:267 The sodium/bile acid cotransporter NTCP was recently identified as a receptor for hepatitis B virus (HBV). 28125599 5 5 theme single 811:816 arg1 variants 832:839 these single glycosylation variants 805:839 these single glycosylation variants 805:839 The physiological function of NTCP, the uptake of bile acids, was also not affected in cells expressing these single glycosylation variants, consistent with their trafficking to the plasma membrane. 28125599 2 6 from role 300:303 arg1 activity 357:364 viral receptor activity 342:364 viral receptor activity 342:364 NTCP is glycosylated and the role of glycans in protein trafficking or viral receptor activity is not known. 28125599 2 6 from role 300:303 arg1 trafficking 327:337 protein trafficking 319:337 protein trafficking 319:337 NTCP is glycosylated and the role of glycans in protein trafficking or viral receptor activity is not known. 28125599 6 7 theme glycosylation-deficient 909:931 arg1 NTCP-N5,11Q 939:949 NTCP-N5,11Q 939:949 NTCP-N5,11Q 939:949 However, glycosylation-deficient NTCP (NTCP-N5,11Q) failed to support HBV infection, showed minimal cellular expression and was degraded in the lysosome. 28125599 6 7 theme glycosylation-deficient 909:931 arg1 NTCP 933:936 glycosylation-deficient NTCP 909:936 glycosylation-deficient NTCP (NTCP-N5,11Q) 909:950 However, glycosylation-deficient NTCP (NTCP-N5,11Q) failed to support HBV infection, showed minimal cellular expression and was degraded in the lysosome. 28125599 4 8 theme HepG2 594:598 arg1 cells 600:604 HepG2 cells 594:604 HepG2 cells expressing NTCP with a single glycan 594:641 HepG2 cells expressing NTCP with a single glycan supported HBV infection at a comparable level to NTCP-WT. 28125599 5 9 theme plasma 883:888 arg1 membrane 890:897 the plasma membrane 879:897 the plasma membrane 879:897 The physiological function of NTCP, the uptake of bile acids, was also not affected in cells expressing these single glycosylation variants, consistent with their trafficking to the plasma membrane. 28125599 4 10 theme single 629:634 arg1 glycan 636:641 a single glycan 627:641 a single glycan 627:641 HepG2 cells expressing NTCP with a single glycan supported HBV infection at a comparable level to NTCP-WT. 28125599 5 11 theme glycosylation 818:830 arg1 variants 832:839 these single glycosylation variants 805:839 these single glycosylation variants 805:839 The physiological function of NTCP, the uptake of bile acids, was also not affected in cells expressing these single glycosylation variants, consistent with their trafficking to the plasma membrane. 28125599 3 12 link N-linked 398:405 arg1 sites 421:425 two N-linked glycosylation sites 394:425 two N-linked glycosylation sites 394:425 NTCP contains two N-linked glycosylation sites and asparagine amino acid residues N5 and N11 were mutated to a glutamine to generate NTCP with a single glycan (NTCP-N5Q or NTCP- N11Q) or no glycans (NTCP- N5,11Q). 28125599 3 13 contain contains 385:392 arg1 NTCP 380:383 NTCP 380:383 NTCP 380:383 NTCP contains two N-linked glycosylation sites and asparagine amino acid residues N5 and N11 were mutated to a glutamine to generate NTCP with a single glycan (NTCP-N5Q or NTCP- N11Q) or no glycans (NTCP- N5,11Q). 28125599 3 13 contain contains 385:392 arg2 sites 421:425 two N-linked glycosylation sites 394:425 two N-linked glycosylation sites 394:425 NTCP contains two N-linked glycosylation sites and asparagine amino acid residues N5 and N11 were mutated to a glutamine to generate NTCP with a single glycan (NTCP-N5Q or NTCP- N11Q) or no glycans (NTCP- N5,11Q). 28125599 3 14 theme N-linked 398:405 arg1 sites 421:425 two N-linked glycosylation sites 394:425 two N-linked glycosylation sites 394:425 NTCP contains two N-linked glycosylation sites and asparagine amino acid residues N5 and N11 were mutated to a glutamine to generate NTCP with a single glycan (NTCP-N5Q or NTCP- N11Q) or no glycans (NTCP- N5,11Q). 28125599 1 15 theme sodium/bile 168:178 arg1 NTCP 199:202 The sodium/bile acid cotransporter NTCP 164:202 The sodium/bile acid cotransporter NTCP 164:202 The sodium/bile acid cotransporter NTCP was recently identified as a receptor for hepatitis B virus (HBV). 28125599 1 15 theme sodium/bile 168:178 arg1 receptor 233:240 a receptor 231:240 a receptor for hepatitis B virus (HBV) 231:268 The sodium/bile acid cotransporter NTCP was recently identified as a receptor for hepatitis B virus (HBV). 28125599 7 16 theme NTCP-N5,11Q 1120:1130 arg1 function 1108:1115 the physiological bile acid transporter function 1068:1115 the physiological bile acid transporter function of NTCP-N5,11Q in a similar fashion 1068:1151 This affected the physiological bile acid transporter function of NTCP-N5,11Q in a similar fashion. 28125599 5 17 theme physiological 705:717 arg1 function 719:726 The physiological function 701:726 The physiological function of NTCP, the uptake of bile acids, 701:761 The physiological function of NTCP, the uptake of bile acids, was also not affected in cells expressing these single glycosylation variants, consistent with their trafficking to the plasma membrane. 28125599 1 18 theme acid 180:183 arg1 NTCP 199:202 The sodium/bile acid cotransporter NTCP 164:202 The sodium/bile acid cotransporter NTCP 164:202 The sodium/bile acid cotransporter NTCP was recently identified as a receptor for hepatitis B virus (HBV). 28125599 1 18 theme acid 180:183 arg1 receptor 233:240 a receptor 231:240 a receptor for hepatitis B virus (HBV) 231:268 The sodium/bile acid cotransporter NTCP was recently identified as a receptor for hepatitis B virus (HBV). 28125599 7 19 theme transporter 1096:1106 arg1 function 1108:1115 the physiological bile acid transporter function 1068:1115 the physiological bile acid transporter function of NTCP-N5,11Q in a similar fashion 1068:1151 This affected the physiological bile acid transporter function of NTCP-N5,11Q in a similar fashion. 28125599 7 20 from function 1108:1115 arg1 fashion 1145:1151 a similar fashion 1135:1151 a similar fashion 1135:1151 This affected the physiological bile acid transporter function of NTCP-N5,11Q in a similar fashion. 28125599 6 21 theme cellular 1000:1007 arg1 expression 1009:1018 minimal cellular expression 992:1018 minimal cellular expression 992:1018 However, glycosylation-deficient NTCP (NTCP-N5,11Q) failed to support HBV infection, showed minimal cellular expression and was degraded in the lysosome. 28125599 1 22 theme cotransporter 185:197 arg1 NTCP 199:202 The sodium/bile acid cotransporter NTCP 164:202 The sodium/bile acid cotransporter NTCP 164:202 The sodium/bile acid cotransporter NTCP was recently identified as a receptor for hepatitis B virus (HBV). 28125599 1 22 theme cotransporter 185:197 arg1 receptor 233:240 a receptor 231:240 a receptor for hepatitis B virus (HBV) 231:268 The sodium/bile acid cotransporter NTCP was recently identified as a receptor for hepatitis B virus (HBV). 28125599 7 23 theme physiological 1072:1084 arg1 function 1108:1115 the physiological bile acid transporter function 1068:1115 the physiological bile acid transporter function of NTCP-N5,11Q in a similar fashion 1068:1151 This affected the physiological bile acid transporter function of NTCP-N5,11Q in a similar fashion. 28125599 3 24 theme glycosylation 407:419 arg1 sites 421:425 two N-linked glycosylation sites 394:425 two N-linked glycosylation sites 394:425 NTCP contains two N-linked glycosylation sites and asparagine amino acid residues N5 and N11 were mutated to a glutamine to generate NTCP with a single glycan (NTCP-N5Q or NTCP- N11Q) or no glycans (NTCP- N5,11Q). 28125599 0 25 theme Na+-Taurocholate 23:38 arg1 Polypeptide 55:65 the Na+-Taurocholate Cotransporting Polypeptide 19:65 the Na+-Taurocholate Cotransporting Polypeptide (NTCP) 19:72 N-Glycosylation of the Na+-Taurocholate Cotransporting Polypeptide (NTCP) Determines Its Trafficking and Stability and Is Required for Hepatitis B Virus Infection. 28125599 0 25 theme Na+-Taurocholate 23:38 arg1 NTCP 68:71 NTCP 68:71 NTCP 68:71 N-Glycosylation of the Na+-Taurocholate Cotransporting Polypeptide (NTCP) Determines Its Trafficking and Stability and Is Required for Hepatitis B Virus Infection. 28125599 8 26 theme single 1340:1345 arg1 moiety 1360:1365 a single carbohydrate moiety 1338:1365 a single carbohydrate moiety 1338:1365 In conclusion, N-glycosylation is required for efficient NTCP localization at the plasma membrane and subsequent HBV infection and these characteristics are preserved in NTCP carrying a single carbohydrate moiety. 28125599 8 27 theme subsequent 1256:1265 arg1 infection 1271:1279 subsequent HBV infection 1256:1279 subsequent HBV infection 1256:1279 In conclusion, N-glycosylation is required for efficient NTCP localization at the plasma membrane and subsequent HBV infection and these characteristics are preserved in NTCP carrying a single carbohydrate moiety. 28125599 3 28 theme NTCP- 552:556 arg1 N11Q 558:561 NTCP- N11Q 552:561 NTCP- N11Q 552:561 NTCP contains two N-linked glycosylation sites and asparagine amino acid residues N5 and N11 were mutated to a glutamine to generate NTCP with a single glycan (NTCP-N5Q or NTCP- N11Q) or no glycans (NTCP- N5,11Q). 28125599 3 29 theme acid 448:451 arg1 N11 469:471 N11 469:471 N11 469:471 NTCP contains two N-linked glycosylation sites and asparagine amino acid residues N5 and N11 were mutated to a glutamine to generate NTCP with a single glycan (NTCP-N5Q or NTCP- N11Q) or no glycans (NTCP- N5,11Q). 28125599 3 29 theme acid 448:451 arg1 N5 462:463 N5 462:463 N5 462:463 NTCP contains two N-linked glycosylation sites and asparagine amino acid residues N5 and N11 were mutated to a glutamine to generate NTCP with a single glycan (NTCP-N5Q or NTCP- N11Q) or no glycans (NTCP- N5,11Q). 28125599 3 29 theme acid 448:451 arg1 residues 453:460 asparagine amino acid residues N5 and N11 431:471 asparagine amino acid residues N5 and N11 431:471 NTCP contains two N-linked glycosylation sites and asparagine amino acid residues N5 and N11 were mutated to a glutamine to generate NTCP with a single glycan (NTCP-N5Q or NTCP- N11Q) or no glycans (NTCP- N5,11Q). 28125599 7 30 theme acid 1091:1094 arg1 function 1108:1115 the physiological bile acid transporter function 1068:1115 the physiological bile acid transporter function of NTCP-N5,11Q in a similar fashion 1068:1151 This affected the physiological bile acid transporter function of NTCP-N5,11Q in a similar fashion. 28125599 3 31 theme single 525:530 arg1 glycan 532:537 a single glycan 523:537 a single glycan (NTCP-N5Q or NTCP- N11Q) 523:562 NTCP contains two N-linked glycosylation sites and asparagine amino acid residues N5 and N11 were mutated to a glutamine to generate NTCP with a single glycan (NTCP-N5Q or NTCP- N11Q) or no glycans (NTCP- N5,11Q). 28125599 5 32 theme acids 756:760 arg1 NTCP 731:734 NTCP 731:734 NTCP 731:734 The physiological function of NTCP, the uptake of bile acids, was also not affected in cells expressing these single glycosylation variants, consistent with their trafficking to the plasma membrane. 28125599 5 32 theme acids 756:760 arg1 uptake 741:746 the uptake 737:746 the uptake of bile acids 737:760 The physiological function of NTCP, the uptake of bile acids, was also not affected in cells expressing these single glycosylation variants, consistent with their trafficking to the plasma membrane. 28125599 0 33 theme Polypeptide 55:65 arg1 N-Glycosylation 0:14 N-Glycosylation 0:14 N-Glycosylation of the Na+-Taurocholate Cotransporting Polypeptide (NTCP) 0:72 N-Glycosylation of the Na+-Taurocholate Cotransporting Polypeptide (NTCP) Determines Its Trafficking and Stability and Is Required for Hepatitis B Virus Infection. 28125599 0 34 theme B 145:145 arg1 Virus 147:151 Hepatitis B Virus 135:151 Hepatitis B Virus Infection 135:161 N-Glycosylation of the Na+-Taurocholate Cotransporting Polypeptide (NTCP) Determines Its Trafficking and Stability and Is Required for Hepatitis B Virus Infection. 28125599 8 35 theme NTCP 1211:1214 arg1 localization 1216:1227 efficient NTCP localization 1201:1227 efficient NTCP localization at the plasma membrane and subsequent HBV infection 1201:1279 In conclusion, N-glycosylation is required for efficient NTCP localization at the plasma membrane and subsequent HBV infection and these characteristics are preserved in NTCP carrying a single carbohydrate moiety. 28125599 0 36 gly N-Glycosylation 0:14 arg1 Polypeptide 55:65 the Na+-Taurocholate Cotransporting Polypeptide 19:65 the Na+-Taurocholate Cotransporting Polypeptide (NTCP) 19:72 N-Glycosylation of the Na+-Taurocholate Cotransporting Polypeptide (NTCP) Determines Its Trafficking and Stability and Is Required for Hepatitis B Virus Infection. 28125599 0 36 gly N-Glycosylation 0:14 arg1 NTCP 68:71 NTCP 68:71 NTCP 68:71 N-Glycosylation of the Na+-Taurocholate Cotransporting Polypeptide (NTCP) Determines Its Trafficking and Stability and Is Required for Hepatitis B Virus Infection. 28125599 8 37 from infection 1271:1279 arg1 localization 1216:1227 efficient NTCP localization 1201:1227 efficient NTCP localization at the plasma membrane and subsequent HBV infection 1201:1279 In conclusion, N-glycosylation is required for efficient NTCP localization at the plasma membrane and subsequent HBV infection and these characteristics are preserved in NTCP carrying a single carbohydrate moiety. 28125599 3 38 theme asparagine 431:440 arg1 N11 469:471 N11 469:471 N11 469:471 NTCP contains two N-linked glycosylation sites and asparagine amino acid residues N5 and N11 were mutated to a glutamine to generate NTCP with a single glycan (NTCP-N5Q or NTCP- N11Q) or no glycans (NTCP- N5,11Q). 28125599 3 38 theme asparagine 431:440 arg1 N5 462:463 N5 462:463 N5 462:463 NTCP contains two N-linked glycosylation sites and asparagine amino acid residues N5 and N11 were mutated to a glutamine to generate NTCP with a single glycan (NTCP-N5Q or NTCP- N11Q) or no glycans (NTCP- N5,11Q). 28125599 3 38 theme asparagine 431:440 arg1 residues 453:460 asparagine amino acid residues N5 and N11 431:471 asparagine amino acid residues N5 and N11 431:471 NTCP contains two N-linked glycosylation sites and asparagine amino acid residues N5 and N11 were mutated to a glutamine to generate NTCP with a single glycan (NTCP-N5Q or NTCP- N11Q) or no glycans (NTCP- N5,11Q). 28125599 0 39 theme Cotransporting 40:53 arg1 Polypeptide 55:65 the Na+-Taurocholate Cotransporting Polypeptide 19:65 the Na+-Taurocholate Cotransporting Polypeptide (NTCP) 19:72 N-Glycosylation of the Na+-Taurocholate Cotransporting Polypeptide (NTCP) Determines Its Trafficking and Stability and Is Required for Hepatitis B Virus Infection. 28125599 0 39 theme Cotransporting 40:53 arg1 NTCP 68:71 NTCP 68:71 NTCP 68:71 N-Glycosylation of the Na+-Taurocholate Cotransporting Polypeptide (NTCP) Determines Its Trafficking and Stability and Is Required for Hepatitis B Virus Infection. 28125599 0 40 theme Hepatitis 135:143 arg1 Virus 147:151 Hepatitis B Virus 135:151 Hepatitis B Virus Infection 135:161 N-Glycosylation of the Na+-Taurocholate Cotransporting Polypeptide (NTCP) Determines Its Trafficking and Stability and Is Required for Hepatitis B Virus Infection. 28125599 8 41 gly N-glycosylation 1169:1183 arg1 conclusion 1157:1166 conclusion 1157:1166 conclusion 1157:1166 In conclusion, N-glycosylation is required for efficient NTCP localization at the plasma membrane and subsequent HBV infection and these characteristics are preserved in NTCP carrying a single carbohydrate moiety. 28125599 8 41 gly N-glycosylation 1169:1183 arg1 NTCP 1211:1214 efficient NTCP localization 1201:1227 efficient NTCP localization at the plasma membrane and subsequent HBV infection 1201:1279 In conclusion, N-glycosylation is required for efficient NTCP localization at the plasma membrane and subsequent HBV infection and these characteristics are preserved in NTCP carrying a single carbohydrate moiety. 28125599 7 42 theme bile 1086:1089 arg1 function 1108:1115 the physiological bile acid transporter function 1068:1115 the physiological bile acid transporter function of NTCP-N5,11Q in a similar fashion 1068:1151 This affected the physiological bile acid transporter function of NTCP-N5,11Q in a similar fashion. 28125599 3 43 theme amino 442:446 arg1 N11 469:471 N11 469:471 N11 469:471 NTCP contains two N-linked glycosylation sites and asparagine amino acid residues N5 and N11 were mutated to a glutamine to generate NTCP with a single glycan (NTCP-N5Q or NTCP- N11Q) or no glycans (NTCP- N5,11Q). 28125599 3 43 theme amino 442:446 arg1 N5 462:463 N5 462:463 N5 462:463 NTCP contains two N-linked glycosylation sites and asparagine amino acid residues N5 and N11 were mutated to a glutamine to generate NTCP with a single glycan (NTCP-N5Q or NTCP- N11Q) or no glycans (NTCP- N5,11Q). 28125599 3 43 theme amino 442:446 arg1 residues 453:460 asparagine amino acid residues N5 and N11 431:471 asparagine amino acid residues N5 and N11 431:471 NTCP contains two N-linked glycosylation sites and asparagine amino acid residues N5 and N11 were mutated to a glutamine to generate NTCP with a single glycan (NTCP-N5Q or NTCP- N11Q) or no glycans (NTCP- N5,11Q). 28125599 8 44 contain carrying 1329:1336 arg2 moiety 1360:1365 a single carbohydrate moiety 1338:1365 a single carbohydrate moiety 1338:1365 In conclusion, N-glycosylation is required for efficient NTCP localization at the plasma membrane and subsequent HBV infection and these characteristics are preserved in NTCP carrying a single carbohydrate moiety. 28125599 8 44 contain carrying 1329:1336 arg1 NTCP 1324:1327 NTCP 1324:1327 NTCP carrying a single carbohydrate moiety 1324:1365 In conclusion, N-glycosylation is required for efficient NTCP localization at the plasma membrane and subsequent HBV infection and these characteristics are preserved in NTCP carrying a single carbohydrate moiety. 28125599 3 45 theme NTCP- 579:583 arg1 N5,11Q 585:590 NTCP- N5,11Q 579:590 NTCP- N5,11Q 579:590 NTCP contains two N-linked glycosylation sites and asparagine amino acid residues N5 and N11 were mutated to a glutamine to generate NTCP with a single glycan (NTCP-N5Q or NTCP- N11Q) or no glycans (NTCP- N5,11Q). 28125599 3 45 theme NTCP- 579:583 arg1 glycans 570:576 no glycans 567:576 no glycans (NTCP- N5,11Q) 567:591 NTCP contains two N-linked glycosylation sites and asparagine amino acid residues N5 and N11 were mutated to a glutamine to generate NTCP with a single glycan (NTCP-N5Q or NTCP- N11Q) or no glycans (NTCP- N5,11Q). 28125599 8 46 theme carbohydrate 1347:1358 arg1 moiety 1360:1365 a single carbohydrate moiety 1338:1365 a single carbohydrate moiety 1338:1365 In conclusion, N-glycosylation is required for efficient NTCP localization at the plasma membrane and subsequent HBV infection and these characteristics are preserved in NTCP carrying a single carbohydrate moiety. 28125599 2 47 theme protein 319:325 arg1 trafficking 327:337 protein trafficking 319:337 protein trafficking 319:337 NTCP is glycosylated and the role of glycans in protein trafficking or viral receptor activity is not known. 28125599 5 48 theme NTCP 731:734 arg1 function 719:726 The physiological function 701:726 The physiological function of NTCP, the uptake of bile acids, 701:761 The physiological function of NTCP, the uptake of bile acids, was also not affected in cells expressing these single glycosylation variants, consistent with their trafficking to the plasma membrane. 28125599 0 49 theme Virus 147:151 arg1 Infection 153:161 Hepatitis B Virus Infection 135:161 Hepatitis B Virus Infection 135:161 N-Glycosylation of the Na+-Taurocholate Cotransporting Polypeptide (NTCP) Determines Its Trafficking and Stability and Is Required for Hepatitis B Virus Infection. 28125599 5 50 with consistent 842:851 arg1 trafficking 864:874 their trafficking 858:874 their trafficking to the plasma membrane 858:897 The physiological function of NTCP, the uptake of bile acids, was also not affected in cells expressing these single glycosylation variants, consistent with their trafficking to the plasma membrane. 28125599 8 51 from membrane 1243:1250 arg1 localization 1216:1227 efficient NTCP localization 1201:1227 efficient NTCP localization at the plasma membrane and subsequent HBV infection 1201:1279 In conclusion, N-glycosylation is required for efficient NTCP localization at the plasma membrane and subsequent HBV infection and these characteristics are preserved in NTCP carrying a single carbohydrate moiety. 28125599 2 52 theme glycans 308:314 arg1 role 300:303 the role 296:303 the role of glycans in protein trafficking or viral receptor activity 296:364 NTCP is glycosylated and the role of glycans in protein trafficking or viral receptor activity is not known. 28125599 4 53 theme comparable 672:681 arg1 level 683:687 a comparable level 670:687 a comparable level to NTCP-WT 670:698 HepG2 cells expressing NTCP with a single glycan supported HBV infection at a comparable level to NTCP-WT. 28125599 4 54 theme HBV 653:655 arg1 infection 657:665 HBV infection 653:665 HBV infection 653:665 HepG2 cells expressing NTCP with a single glycan supported HBV infection at a comparable level to NTCP-WT. 28125599 8 55 theme HBV 1267:1269 arg1 infection 1271:1279 subsequent HBV infection 1256:1279 subsequent HBV infection 1256:1279 In conclusion, N-glycosylation is required for efficient NTCP localization at the plasma membrane and subsequent HBV infection and these characteristics are preserved in NTCP carrying a single carbohydrate moiety. 28125599 8 56 theme plasma 1236:1241 arg1 membrane 1243:1250 the plasma membrane 1232:1250 the plasma membrane 1232:1250 In conclusion, N-glycosylation is required for efficient NTCP localization at the plasma membrane and subsequent HBV infection and these characteristics are preserved in NTCP carrying a single carbohydrate moiety. 28125599 8 57 theme efficient 1201:1209 arg1 localization 1216:1227 efficient NTCP localization 1201:1227 efficient NTCP localization at the plasma membrane and subsequent HBV infection 1201:1279 In conclusion, N-glycosylation is required for efficient NTCP localization at the plasma membrane and subsequent HBV infection and these characteristics are preserved in NTCP carrying a single carbohydrate moiety. 28125599 3 58 gly glycosylation 407:419 arg2 two 394:396 two 394:396 two 394:396 NTCP contains two N-linked glycosylation sites and asparagine amino acid residues N5 and N11 were mutated to a glutamine to generate NTCP with a single glycan (NTCP-N5Q or NTCP- N11Q) or no glycans (NTCP- N5,11Q). 28125599 3 58 gly glycosylation 407:419 arg2 sites 421:425 two N-linked glycosylation sites 394:425 two N-linked glycosylation sites 394:425 NTCP contains two N-linked glycosylation sites and asparagine amino acid residues N5 and N11 were mutated to a glutamine to generate NTCP with a single glycan (NTCP-N5Q or NTCP- N11Q) or no glycans (NTCP- N5,11Q). 28125599 5 59 theme bile 751:754 arg1 acids 756:760 bile acids 751:760 bile acids 751:760 The physiological function of NTCP, the uptake of bile acids, was also not affected in cells expressing these single glycosylation variants, consistent with their trafficking to the plasma membrane. 28125599 2 60 theme receptor 348:355 arg1 activity 357:364 viral receptor activity 342:364 viral receptor activity 342:364 NTCP is glycosylated and the role of glycans in protein trafficking or viral receptor activity is not known. 28125599 6 61 theme minimal 992:998 arg1 expression 1009:1018 minimal cellular expression 992:1018 minimal cellular expression 992:1018 However, glycosylation-deficient NTCP (NTCP-N5,11Q) failed to support HBV infection, showed minimal cellular expression and was degraded in the lysosome. 28125599 3 62 dep residues 453:460 arg1 N11 469:471 N11 469:471 N11 469:471 NTCP contains two N-linked glycosylation sites and asparagine amino acid residues N5 and N11 were mutated to a glutamine to generate NTCP with a single glycan (NTCP-N5Q or NTCP- N11Q) or no glycans (NTCP- N5,11Q). 28125599 3 62 dep residues 453:460 arg1 N5 462:463 N5 462:463 N5 462:463 NTCP contains two N-linked glycosylation sites and asparagine amino acid residues N5 and N11 were mutated to a glutamine to generate NTCP with a single glycan (NTCP-N5Q or NTCP- N11Q) or no glycans (NTCP- N5,11Q). 28125599 3 62 dep residues 453:460 arg1 residues 453:460 asparagine amino acid residues N5 and N11 431:471 asparagine amino acid residues N5 and N11 431:471 NTCP contains two N-linked glycosylation sites and asparagine amino acid residues N5 and N11 were mutated to a glutamine to generate NTCP with a single glycan (NTCP-N5Q or NTCP- N11Q) or no glycans (NTCP- N5,11Q). 28125599 2 63 theme viral 342:346 arg1 activity 357:364 viral receptor activity 342:364 viral receptor activity 342:364 NTCP is glycosylated and the role of glycans in protein trafficking or viral receptor activity is not known. 28125599 1 64 theme hepatitis 246:254 arg1 virus 258:262 hepatitis B virus 246:262 hepatitis B virus (HBV) 246:268 The sodium/bile acid cotransporter NTCP was recently identified as a receptor for hepatitis B virus (HBV). 28125599 1 64 theme hepatitis 246:254 arg1 HBV 265:267 HBV 265:267 HBV 265:267 The sodium/bile acid cotransporter NTCP was recently identified as a receptor for hepatitis B virus (HBV). 26384088 4 0 theme distribution 814:825 arg1 pattern 827:833 a unique PNGS distribution pattern 800:833 a unique PNGS distribution pattern 800:833 HIV-1 subtype CRF01_AE has a unique PNGS distribution pattern in Gp120, which may contribute to its advantage in sexual transmission in China. 26384088 3 1 theme fewer 691:695 arg1 PNGSs 697:701 significantly fewer PNGSs 677:701 significantly fewer PNGSs 677:701 Compared to CRF07_BC, CRF08_BC, B, and B' subtypes isolated in China, CRF01_AE subtypes isolated from both China and outside China had significantly fewer PNGSs in total and in V2/V4, while they had significantly more PNGSs in V5. 26384088 3 2 contain had 673:675 arg2 PNGSs 697:701 significantly fewer PNGSs 677:701 significantly fewer PNGSs 677:701 Compared to CRF07_BC, CRF08_BC, B, and B' subtypes isolated in China, CRF01_AE subtypes isolated from both China and outside China had significantly fewer PNGSs in total and in V2/V4, while they had significantly more PNGSs in V5. 26384088 3 2 contain had 673:675 arg1 subtypes 621:628 CRF01_AE subtypes 612:628 CRF01_AE subtypes isolated from both China and outside China 612:671 Compared to CRF07_BC, CRF08_BC, B, and B' subtypes isolated in China, CRF01_AE subtypes isolated from both China and outside China had significantly fewer PNGSs in total and in V2/V4, while they had significantly more PNGSs in V5. 26384088 2 3 from absence 301:307 arg1 loops 371:375 variable loops 362:375 variable loops 362:375 Previous studies showed that the presence or absence of potential N-linked glycosylation sites (PNGSs) in variable loops might affect HIV-1 transmission; it is therefore of interest to compare the distribution of potential PNGSs on envelopes of different subtypes circulating in China. 26384088 2 4 theme PNGSs 479:483 arg1 distribution 453:464 the distribution 449:464 the distribution of potential PNGSs on envelopes of different subtypes circulating in China 449:539 Previous studies showed that the presence or absence of potential N-linked glycosylation sites (PNGSs) in variable loops might affect HIV-1 transmission; it is therefore of interest to compare the distribution of potential PNGSs on envelopes of different subtypes circulating in China. 26384088 4 5 theme PNGS 809:812 arg1 pattern 827:833 a unique PNGS distribution pattern 800:833 a unique PNGS distribution pattern 800:833 HIV-1 subtype CRF01_AE has a unique PNGS distribution pattern in Gp120, which may contribute to its advantage in sexual transmission in China. 26384088 2 6 dep presence 289:296 arg1 the 285:287 the 285:287 the 285:287 Previous studies showed that the presence or absence of potential N-linked glycosylation sites (PNGSs) in variable loops might affect HIV-1 transmission; it is therefore of interest to compare the distribution of potential PNGSs on envelopes of different subtypes circulating in China. 26384088 2 7 theme different 501:509 arg1 subtypes 511:518 different subtypes 501:518 different subtypes circulating in China 501:539 Previous studies showed that the presence or absence of potential N-linked glycosylation sites (PNGSs) in variable loops might affect HIV-1 transmission; it is therefore of interest to compare the distribution of potential PNGSs on envelopes of different subtypes circulating in China. 26384088 4 8 theme sexual 886:891 arg1 transmission 893:904 sexual transmission 886:904 sexual transmission in China 886:913 HIV-1 subtype CRF01_AE has a unique PNGS distribution pattern in Gp120, which may contribute to its advantage in sexual transmission in China. 26384088 2 9 from distribution 453:464 arg1 envelopes 488:496 envelopes 488:496 envelopes of different subtypes circulating in China 488:539 Previous studies showed that the presence or absence of potential N-linked glycosylation sites (PNGSs) in variable loops might affect HIV-1 transmission; it is therefore of interest to compare the distribution of potential PNGSs on envelopes of different subtypes circulating in China. 26384088 2 10 theme subtypes 511:518 arg1 envelopes 488:496 envelopes 488:496 envelopes of different subtypes circulating in China 488:539 Previous studies showed that the presence or absence of potential N-linked glycosylation sites (PNGSs) in variable loops might affect HIV-1 transmission; it is therefore of interest to compare the distribution of potential PNGSs on envelopes of different subtypes circulating in China. 26384088 3 11 contain had 737:739 arg1 they 732:735 they 732:735 they 732:735 Compared to CRF07_BC, CRF08_BC, B, and B' subtypes isolated in China, CRF01_AE subtypes isolated from both China and outside China had significantly fewer PNGSs in total and in V2/V4, while they had significantly more PNGSs in V5. 26384088 3 11 contain had 737:739 arg2 PNGSs 760:764 significantly more PNGSs 741:764 significantly more PNGSs 741:764 Compared to CRF07_BC, CRF08_BC, B, and B' subtypes isolated in China, CRF01_AE subtypes isolated from both China and outside China had significantly fewer PNGSs in total and in V2/V4, while they had significantly more PNGSs in V5. 26384088 1 12 theme obvious 164:170 arg1 advantage 192:200 an obvious sexual transmission advantage 161:200 an obvious sexual transmission advantage over other major HIV-1 subtypes circulating in China 161:253 CRF01_AE shows an obvious sexual transmission advantage over other major HIV-1 subtypes circulating in China. 26384088 0 13 theme Major 103:107 arg1 Subtypes 115:122 Major HIV-1 Subtypes 103:122 Major HIV-1 Subtypes Circulating in China 103:143 Short Communication: The Distribution of Potential N-Linked Glycosylation Sites in Gp120 Differs Among Major HIV-1 Subtypes Circulating in China. 26384088 1 14 theme sexual 172:177 arg1 advantage 192:200 an obvious sexual transmission advantage 161:200 an obvious sexual transmission advantage over other major HIV-1 subtypes circulating in China 161:253 CRF01_AE shows an obvious sexual transmission advantage over other major HIV-1 subtypes circulating in China. 26384088 0 15 from Distribution 25:36 arg1 Gp120 83:87 Gp120 83:87 Gp120 83:87 Short Communication: The Distribution of Potential N-Linked Glycosylation Sites in Gp120 Differs Among Major HIV-1 Subtypes Circulating in China. 26384088 4 16 theme unique 802:807 arg1 pattern 827:833 a unique PNGS distribution pattern 800:833 a unique PNGS distribution pattern 800:833 HIV-1 subtype CRF01_AE has a unique PNGS distribution pattern in Gp120, which may contribute to its advantage in sexual transmission in China. 26384088 2 17 theme N-linked 322:329 arg1 PNGSs 352:356 PNGSs 352:356 PNGSs 352:356 Previous studies showed that the presence or absence of potential N-linked glycosylation sites (PNGSs) in variable loops might affect HIV-1 transmission; it is therefore of interest to compare the distribution of potential PNGSs on envelopes of different subtypes circulating in China. 26384088 2 17 theme N-linked 322:329 arg1 sites 345:349 potential N-linked glycosylation sites 312:349 potential N-linked glycosylation sites (PNGSs) 312:357 Previous studies showed that the presence or absence of potential N-linked glycosylation sites (PNGSs) in variable loops might affect HIV-1 transmission; it is therefore of interest to compare the distribution of potential PNGSs on envelopes of different subtypes circulating in China. 26384088 1 18 theme transmission 179:190 arg1 advantage 192:200 an obvious sexual transmission advantage 161:200 an obvious sexual transmission advantage over other major HIV-1 subtypes circulating in China 161:253 CRF01_AE shows an obvious sexual transmission advantage over other major HIV-1 subtypes circulating in China. 26384088 0 19 theme Short 0:4 arg1 Communication 6:18 Short Communication 0:18 Short Communication: The Distribution of Potential N-Linked Glycosylation Sites in Gp120 Differs Among Major HIV-1 Subtypes Circulating in China. 0:144 Short Communication: The Distribution of Potential N-Linked Glycosylation Sites in Gp120 Differs Among Major HIV-1 Subtypes Circulating in China. 26384088 2 20 theme potential 312:320 arg1 PNGSs 352:356 PNGSs 352:356 PNGSs 352:356 Previous studies showed that the presence or absence of potential N-linked glycosylation sites (PNGSs) in variable loops might affect HIV-1 transmission; it is therefore of interest to compare the distribution of potential PNGSs on envelopes of different subtypes circulating in China. 26384088 2 20 theme potential 312:320 arg1 sites 345:349 potential N-linked glycosylation sites 312:349 potential N-linked glycosylation sites (PNGSs) 312:357 Previous studies showed that the presence or absence of potential N-linked glycosylation sites (PNGSs) in variable loops might affect HIV-1 transmission; it is therefore of interest to compare the distribution of potential PNGSs on envelopes of different subtypes circulating in China. 26384088 2 21 theme Previous 256:263 arg1 studies 265:271 Previous studies 256:271 Previous studies 256:271 Previous studies showed that the presence or absence of potential N-linked glycosylation sites (PNGSs) in variable loops might affect HIV-1 transmission; it is therefore of interest to compare the distribution of potential PNGSs on envelopes of different subtypes circulating in China. 26384088 3 22 attach isolated 630:637 arg2 subtypes 621:628 CRF01_AE subtypes 612:628 CRF01_AE subtypes isolated from both China and outside China 612:671 Compared to CRF07_BC, CRF08_BC, B, and B' subtypes isolated in China, CRF01_AE subtypes isolated from both China and outside China had significantly fewer PNGSs in total and in V2/V4, while they had significantly more PNGSs in V5. 26384088 3 22 attach isolated 630:637 arg1 China 649:653 both China 644:653 both China 644:653 Compared to CRF07_BC, CRF08_BC, B, and B' subtypes isolated in China, CRF01_AE subtypes isolated from both China and outside China had significantly fewer PNGSs in total and in V2/V4, while they had significantly more PNGSs in V5. 26384088 4 23 from advantage 873:881 arg1 transmission 893:904 sexual transmission 886:904 sexual transmission in China 886:913 HIV-1 subtype CRF01_AE has a unique PNGS distribution pattern in Gp120, which may contribute to its advantage in sexual transmission in China. 26384088 3 24 theme CRF01_AE 612:619 arg1 subtypes 621:628 CRF01_AE subtypes 612:628 CRF01_AE subtypes isolated from both China and outside China 612:671 Compared to CRF07_BC, CRF08_BC, B, and B' subtypes isolated in China, CRF01_AE subtypes isolated from both China and outside China had significantly fewer PNGSs in total and in V2/V4, while they had significantly more PNGSs in V5. 26384088 1 25 theme other 207:211 arg1 subtypes 225:232 other major HIV-1 subtypes 207:232 other major HIV-1 subtypes circulating in China 207:253 CRF01_AE shows an obvious sexual transmission advantage over other major HIV-1 subtypes circulating in China. 26384088 2 26 theme potential 469:477 arg1 PNGSs 479:483 potential PNGSs 469:483 potential PNGSs 469:483 Previous studies showed that the presence or absence of potential N-linked glycosylation sites (PNGSs) in variable loops might affect HIV-1 transmission; it is therefore of interest to compare the distribution of potential PNGSs on envelopes of different subtypes circulating in China. 26384088 0 27 theme HIV-1 109:113 arg1 Subtypes 115:122 Major HIV-1 Subtypes 103:122 Major HIV-1 Subtypes Circulating in China 103:143 Short Communication: The Distribution of Potential N-Linked Glycosylation Sites in Gp120 Differs Among Major HIV-1 Subtypes Circulating in China. 26384088 2 28 from presence 289:296 arg1 loops 371:375 variable loops 362:375 variable loops 362:375 Previous studies showed that the presence or absence of potential N-linked glycosylation sites (PNGSs) in variable loops might affect HIV-1 transmission; it is therefore of interest to compare the distribution of potential PNGSs on envelopes of different subtypes circulating in China. 26384088 1 29 theme major 213:217 arg1 subtypes 225:232 other major HIV-1 subtypes 207:232 other major HIV-1 subtypes circulating in China 207:253 CRF01_AE shows an obvious sexual transmission advantage over other major HIV-1 subtypes circulating in China. 26384088 2 30 attach presence 289:296 arg2 PNGSs 352:356 PNGSs 352:356 PNGSs 352:356 Previous studies showed that the presence or absence of potential N-linked glycosylation sites (PNGSs) in variable loops might affect HIV-1 transmission; it is therefore of interest to compare the distribution of potential PNGSs on envelopes of different subtypes circulating in China. 26384088 2 30 attach presence 289:296 arg2 sites 345:349 potential N-linked glycosylation sites 312:349 potential N-linked glycosylation sites (PNGSs) 312:357 Previous studies showed that the presence or absence of potential N-linked glycosylation sites (PNGSs) in variable loops might affect HIV-1 transmission; it is therefore of interest to compare the distribution of potential PNGSs on envelopes of different subtypes circulating in China. 26384088 2 30 attach presence 289:296 arg1 loops 371:375 variable loops 362:375 variable loops 362:375 Previous studies showed that the presence or absence of potential N-linked glycosylation sites (PNGSs) in variable loops might affect HIV-1 transmission; it is therefore of interest to compare the distribution of potential PNGSs on envelopes of different subtypes circulating in China. 26384088 4 31 from transmission 893:904 arg1 China 909:913 China 909:913 China 909:913 HIV-1 subtype CRF01_AE has a unique PNGS distribution pattern in Gp120, which may contribute to its advantage in sexual transmission in China. 26384088 1 32 theme HIV-1 219:223 arg1 subtypes 225:232 other major HIV-1 subtypes 207:232 other major HIV-1 subtypes circulating in China 207:253 CRF01_AE shows an obvious sexual transmission advantage over other major HIV-1 subtypes circulating in China. 26384088 0 33 theme N-Linked 51:58 arg1 Sites 74:78 Potential N-Linked Glycosylation Sites 41:78 Potential N-Linked Glycosylation Sites 41:78 Short Communication: The Distribution of Potential N-Linked Glycosylation Sites in Gp120 Differs Among Major HIV-1 Subtypes Circulating in China. 26384088 4 34 theme subtype 779:785 arg1 CRF01_AE 787:794 HIV-1 subtype CRF01_AE 773:794 HIV-1 subtype CRF01_AE 773:794 HIV-1 subtype CRF01_AE has a unique PNGS distribution pattern in Gp120, which may contribute to its advantage in sexual transmission in China. 26384088 0 35 theme Potential 41:49 arg1 Sites 74:78 Potential N-Linked Glycosylation Sites 41:78 Potential N-Linked Glycosylation Sites 41:78 Short Communication: The Distribution of Potential N-Linked Glycosylation Sites in Gp120 Differs Among Major HIV-1 Subtypes Circulating in China. 26384088 2 36 link N-linked 322:329 arg1 PNGSs 352:356 PNGSs 352:356 PNGSs 352:356 Previous studies showed that the presence or absence of potential N-linked glycosylation sites (PNGSs) in variable loops might affect HIV-1 transmission; it is therefore of interest to compare the distribution of potential PNGSs on envelopes of different subtypes circulating in China. 26384088 2 36 link N-linked 322:329 arg1 sites 345:349 potential N-linked glycosylation sites 312:349 potential N-linked glycosylation sites (PNGSs) 312:357 Previous studies showed that the presence or absence of potential N-linked glycosylation sites (PNGSs) in variable loops might affect HIV-1 transmission; it is therefore of interest to compare the distribution of potential PNGSs on envelopes of different subtypes circulating in China. 26384088 4 37 theme HIV-1 773:777 arg1 CRF01_AE 787:794 HIV-1 subtype CRF01_AE 773:794 HIV-1 subtype CRF01_AE 773:794 HIV-1 subtype CRF01_AE has a unique PNGS distribution pattern in Gp120, which may contribute to its advantage in sexual transmission in China. 26384088 4 38 contain has 796:798 arg1 CRF01_AE 787:794 HIV-1 subtype CRF01_AE 773:794 HIV-1 subtype CRF01_AE 773:794 HIV-1 subtype CRF01_AE has a unique PNGS distribution pattern in Gp120, which may contribute to its advantage in sexual transmission in China. 26384088 4 38 contain has 796:798 arg2 pattern 827:833 a unique PNGS distribution pattern 800:833 a unique PNGS distribution pattern 800:833 HIV-1 subtype CRF01_AE has a unique PNGS distribution pattern in Gp120, which may contribute to its advantage in sexual transmission in China. 26384088 2 39 gly glycosylation 331:343 arg2 PNGSs 352:356 PNGSs 352:356 PNGSs 352:356 Previous studies showed that the presence or absence of potential N-linked glycosylation sites (PNGSs) in variable loops might affect HIV-1 transmission; it is therefore of interest to compare the distribution of potential PNGSs on envelopes of different subtypes circulating in China. 26384088 2 39 gly glycosylation 331:343 arg2 sites 345:349 potential N-linked glycosylation sites 312:349 potential N-linked glycosylation sites (PNGSs) 312:357 Previous studies showed that the presence or absence of potential N-linked glycosylation sites (PNGSs) in variable loops might affect HIV-1 transmission; it is therefore of interest to compare the distribution of potential PNGSs on envelopes of different subtypes circulating in China. 26384088 2 40 theme sites 345:349 arg1 presence 289:296 presence 289:296 presence 289:296 Previous studies showed that the presence or absence of potential N-linked glycosylation sites (PNGSs) in variable loops might affect HIV-1 transmission; it is therefore of interest to compare the distribution of potential PNGSs on envelopes of different subtypes circulating in China. 26384088 2 40 theme sites 345:349 arg1 absence 301:307 absence 301:307 absence 301:307 Previous studies showed that the presence or absence of potential N-linked glycosylation sites (PNGSs) in variable loops might affect HIV-1 transmission; it is therefore of interest to compare the distribution of potential PNGSs on envelopes of different subtypes circulating in China. 26384088 2 41 theme glycosylation 331:343 arg1 PNGSs 352:356 PNGSs 352:356 PNGSs 352:356 Previous studies showed that the presence or absence of potential N-linked glycosylation sites (PNGSs) in variable loops might affect HIV-1 transmission; it is therefore of interest to compare the distribution of potential PNGSs on envelopes of different subtypes circulating in China. 26384088 2 41 theme glycosylation 331:343 arg1 sites 345:349 potential N-linked glycosylation sites 312:349 potential N-linked glycosylation sites (PNGSs) 312:357 Previous studies showed that the presence or absence of potential N-linked glycosylation sites (PNGSs) in variable loops might affect HIV-1 transmission; it is therefore of interest to compare the distribution of potential PNGSs on envelopes of different subtypes circulating in China. 26384088 0 42 theme Sites 74:78 arg1 Distribution 25:36 The Distribution 21:36 The Distribution of Potential N-Linked Glycosylation Sites in Gp120 21:87 Short Communication: The Distribution of Potential N-Linked Glycosylation Sites in Gp120 Differs Among Major HIV-1 Subtypes Circulating in China. 26384088 0 43 dep Communication 6:18 arg1 Differs 89:95 Differs 89:95 Differs Among Major HIV-1 Subtypes Circulating in China 89:143 Short Communication: The Distribution of Potential N-Linked Glycosylation Sites in Gp120 Differs Among Major HIV-1 Subtypes Circulating in China. 26384088 2 44 theme HIV-1 390:394 arg1 transmission 396:407 HIV-1 transmission 390:407 HIV-1 transmission 390:407 Previous studies showed that the presence or absence of potential N-linked glycosylation sites (PNGSs) in variable loops might affect HIV-1 transmission; it is therefore of interest to compare the distribution of potential PNGSs on envelopes of different subtypes circulating in China. 26384088 0 45 theme Glycosylation 60:72 arg1 Sites 74:78 Potential N-Linked Glycosylation Sites 41:78 Potential N-Linked Glycosylation Sites 41:78 Short Communication: The Distribution of Potential N-Linked Glycosylation Sites in Gp120 Differs Among Major HIV-1 Subtypes Circulating in China. 26384088 2 46 theme variable 362:369 arg1 loops 371:375 variable loops 362:375 variable loops 362:375 Previous studies showed that the presence or absence of potential N-linked glycosylation sites (PNGSs) in variable loops might affect HIV-1 transmission; it is therefore of interest to compare the distribution of potential PNGSs on envelopes of different subtypes circulating in China. 26384088 3 47 theme more 755:758 arg1 PNGSs 760:764 significantly more PNGSs 741:764 significantly more PNGSs 741:764 Compared to CRF07_BC, CRF08_BC, B, and B' subtypes isolated in China, CRF01_AE subtypes isolated from both China and outside China had significantly fewer PNGSs in total and in V2/V4, while they had significantly more PNGSs in V5. 25289757 0 0 theme receptors 67:75 arg1 N-terminus 30:39 the N-terminus 26:39 the N-terminus of the dopamine D2 and D3 receptors 26:75 N-linked Glycosylation on the N-terminus of the dopamine D2 and D3 receptors determines receptor association with specific microdomains in the plasma membrane. 25289757 7 1 theme GPCRs 1388:1392 arg1 N-terminus 1374:1383 the N-terminus 1370:1383 the N-terminus of GPCRs 1370:1392 In conclusion, this study shows for the first time that glycosylation on the N-terminus of GPCRs is involved in endocytic pathway selection through specific microdomains. 25289757 4 2 gly glycosylation 675:687 arg2 site 689:692 the glycosylation site mutant 671:699 the glycosylation site mutant D₂and D₃receptors to study the roles of glycosylation on receptor functions, including cell surface expression, signaling, and internalization through specific microdomains 671:872 We used the pharmacological inhibitor, tunicamycin, to inhibit glycosylation, generated chimeric D₂and D₃receptors by swapping their respective N-termini, and produced the glycosylation site mutant D₂and D₃receptors to study the roles of glycosylation on receptor functions, including cell surface expression, signaling, and internalization through specific microdomains. 25289757 4 2 gly glycosylation 675:687 arg2 mutant 694:699 the glycosylation site mutant 671:699 the glycosylation site mutant D₂and D₃receptors to study the roles of glycosylation on receptor functions, including cell surface expression, signaling, and internalization through specific microdomains 671:872 We used the pharmacological inhibitor, tunicamycin, to inhibit glycosylation, generated chimeric D₂and D₃receptors by swapping their respective N-termini, and produced the glycosylation site mutant D₂and D₃receptors to study the roles of glycosylation on receptor functions, including cell surface expression, signaling, and internalization through specific microdomains. 25289757 5 3 theme D₃ 943:944 arg1 receptor 946:953 the D₃ receptor 939:953 the D₃ receptor 939:953 Our results demonstrate that glycosylation on the N-terminus of the D₃ receptor is involved in the development of desensitization and proper cell surface expression. 25289757 4 4 theme D₂and 600:604 arg1 D₃receptors 606:616 chimeric D₂and D₃receptors 591:616 chimeric D₂and D₃receptors 591:616 We used the pharmacological inhibitor, tunicamycin, to inhibit glycosylation, generated chimeric D₂and D₃receptors by swapping their respective N-termini, and produced the glycosylation site mutant D₂and D₃receptors to study the roles of glycosylation on receptor functions, including cell surface expression, signaling, and internalization through specific microdomains. 25289757 0 5 theme D3 64:65 arg1 receptors 67:75 the dopamine D2 and D3 receptors 44:75 the dopamine D2 and D3 receptors 44:75 N-linked Glycosylation on the N-terminus of the dopamine D2 and D3 receptors determines receptor association with specific microdomains in the plasma membrane. 25289757 0 6 from Glycosylation 9:21 arg1 N-terminus 30:39 the N-terminus 26:39 the N-terminus of the dopamine D2 and D3 receptors 26:75 N-linked Glycosylation on the N-terminus of the dopamine D2 and D3 receptors determines receptor association with specific microdomains in the plasma membrane. 25289757 5 7 gly glycosylation 904:916 arg1 development 974:984 the development 970:984 the development of desensitization and proper cell surface expression 970:1038 Our results demonstrate that glycosylation on the N-terminus of the D₃ receptor is involved in the development of desensitization and proper cell surface expression. 25289757 5 7 gly glycosylation 904:916 arg1 N-terminus 925:934 the N-terminus 921:934 the N-terminus of the D₃ receptor 921:953 Our results demonstrate that glycosylation on the N-terminus of the D₃ receptor is involved in the development of desensitization and proper cell surface expression. 25289757 1 8 theme Numerous 160:167 arg1 receptors 187:195 Numerous G protein-coupled receptors 160:195 Numerous G protein-coupled receptors (GPCRs) 160:203 Numerous G protein-coupled receptors (GPCRs) are glycosylated at extracellular regions. 25289757 1 8 theme Numerous 160:167 arg1 GPCRs 198:202 GPCRs 198:202 GPCRs 198:202 Numerous G protein-coupled receptors (GPCRs) are glycosylated at extracellular regions. 25289757 4 9 theme chimeric 591:598 arg1 D₃receptors 606:616 chimeric D₂and D₃receptors 591:616 chimeric D₂and D₃receptors 591:616 We used the pharmacological inhibitor, tunicamycin, to inhibit glycosylation, generated chimeric D₂and D₃receptors by swapping their respective N-termini, and produced the glycosylation site mutant D₂and D₃receptors to study the roles of glycosylation on receptor functions, including cell surface expression, signaling, and internalization through specific microdomains. 25289757 0 10 theme receptor 88:95 arg1 association 97:107 receptor association 88:107 receptor association with specific microdomains in the plasma membrane 88:157 N-linked Glycosylation on the N-terminus of the dopamine D2 and D3 receptors determines receptor association with specific microdomains in the plasma membrane. 25289757 4 11 theme pharmacological 515:529 arg1 tunicamycin 542:552 tunicamycin 542:552 tunicamycin 542:552 We used the pharmacological inhibitor, tunicamycin, to inhibit glycosylation, generated chimeric D₂and D₃receptors by swapping their respective N-termini, and produced the glycosylation site mutant D₂and D₃receptors to study the roles of glycosylation on receptor functions, including cell surface expression, signaling, and internalization through specific microdomains. 25289757 4 11 theme pharmacological 515:529 arg1 inhibitor 531:539 the pharmacological inhibitor 511:539 the pharmacological inhibitor 511:539 We used the pharmacological inhibitor, tunicamycin, to inhibit glycosylation, generated chimeric D₂and D₃receptors by swapping their respective N-termini, and produced the glycosylation site mutant D₂and D₃receptors to study the roles of glycosylation on receptor functions, including cell surface expression, signaling, and internalization through specific microdomains. 25289757 4 12 theme surface 793:799 arg1 expression 801:810 cell surface expression 788:810 cell surface expression 788:810 We used the pharmacological inhibitor, tunicamycin, to inhibit glycosylation, generated chimeric D₂and D₃receptors by swapping their respective N-termini, and produced the glycosylation site mutant D₂and D₃receptors to study the roles of glycosylation on receptor functions, including cell surface expression, signaling, and internalization through specific microdomains. 25289757 6 13 theme membrane 1207:1214 arg1 caveolae 1147:1154 the caveolae and clathrin-coated pit microdomains 1143:1191 caveolae 1147:1154 In addition, glycosylation on the N-terminus mediates the internalization of D₂and D₃receptors within the caveolae and clathrin-coated pit microdomains of the plasma membrane, respectively, by regulating receptor interactions with caveolin-1 and clathrin. 25289757 6 13 theme membrane 1207:1214 arg1 membrane 1207:1214 the plasma membrane 1196:1214 the plasma membrane 1196:1214 In addition, glycosylation on the N-terminus mediates the internalization of D₂and D₃receptors within the caveolae and clathrin-coated pit microdomains of the plasma membrane, respectively, by regulating receptor interactions with caveolin-1 and clathrin. 25289757 6 13 theme membrane 1207:1214 arg1 microdomains 1180:1191 the caveolae and clathrin-coated pit microdomains 1143:1191 microdomains 1180:1191 In addition, glycosylation on the N-terminus mediates the internalization of D₂and D₃receptors within the caveolae and clathrin-coated pit microdomains of the plasma membrane, respectively, by regulating receptor interactions with caveolin-1 and clathrin. 25289757 8 14 theme trafficking 1630:1640 arg1 determinant 1596:1606 an important determinant 1583:1606 an important determinant of intracellular GPCR trafficking 1583:1640 These data suggest that changes in the cellular environment that influence posttranslational modification could be an important determinant of intracellular GPCR trafficking. 25289757 8 14 theme trafficking 1630:1640 arg1 changes 1492:1498 changes 1492:1498 changes in the cellular environment that influence posttranslational modification 1492:1572 These data suggest that changes in the cellular environment that influence posttranslational modification could be an important determinant of intracellular GPCR trafficking. 25289757 4 15 theme cell 788:791 arg1 expression 801:810 cell surface expression 788:810 cell surface expression 788:810 We used the pharmacological inhibitor, tunicamycin, to inhibit glycosylation, generated chimeric D₂and D₃receptors by swapping their respective N-termini, and produced the glycosylation site mutant D₂and D₃receptors to study the roles of glycosylation on receptor functions, including cell surface expression, signaling, and internalization through specific microdomains. 25289757 2 16 theme receptor 289:296 arg1 function 298:305 receptor function 289:305 receptor function 289:305 The regulatory roles of glycosylation on receptor function vary across receptor types. 25289757 4 17 from roles 732:736 arg1 signaling 813:821 signaling 813:821 signaling 813:821 We used the pharmacological inhibitor, tunicamycin, to inhibit glycosylation, generated chimeric D₂and D₃receptors by swapping their respective N-termini, and produced the glycosylation site mutant D₂and D₃receptors to study the roles of glycosylation on receptor functions, including cell surface expression, signaling, and internalization through specific microdomains. 25289757 4 17 from roles 732:736 arg1 internalization 828:842 internalization 828:842 internalization 828:842 We used the pharmacological inhibitor, tunicamycin, to inhibit glycosylation, generated chimeric D₂and D₃receptors by swapping their respective N-termini, and produced the glycosylation site mutant D₂and D₃receptors to study the roles of glycosylation on receptor functions, including cell surface expression, signaling, and internalization through specific microdomains. 25289757 4 17 from roles 732:736 arg1 expression 801:810 cell surface expression 788:810 cell surface expression 788:810 We used the pharmacological inhibitor, tunicamycin, to inhibit glycosylation, generated chimeric D₂and D₃receptors by swapping their respective N-termini, and produced the glycosylation site mutant D₂and D₃receptors to study the roles of glycosylation on receptor functions, including cell surface expression, signaling, and internalization through specific microdomains. 25289757 4 17 from roles 732:736 arg1 functions 767:775 receptor functions 758:775 receptor functions 758:775 We used the pharmacological inhibitor, tunicamycin, to inhibit glycosylation, generated chimeric D₂and D₃receptors by swapping their respective N-termini, and produced the glycosylation site mutant D₂and D₃receptors to study the roles of glycosylation on receptor functions, including cell surface expression, signaling, and internalization through specific microdomains. 25289757 4 18 theme glycosylation 741:753 arg1 roles 732:736 the roles 728:736 the roles of glycosylation on receptor functions, including cell surface expression, signaling, and internalization through specific microdomains 728:872 We used the pharmacological inhibitor, tunicamycin, to inhibit glycosylation, generated chimeric D₂and D₃receptors by swapping their respective N-termini, and produced the glycosylation site mutant D₂and D₃receptors to study the roles of glycosylation on receptor functions, including cell surface expression, signaling, and internalization through specific microdomains. 25289757 8 19 theme GPCR 1625:1628 arg1 trafficking 1630:1640 intracellular GPCR trafficking 1611:1640 intracellular GPCR trafficking 1611:1640 These data suggest that changes in the cellular environment that influence posttranslational modification could be an important determinant of intracellular GPCR trafficking. 25289757 0 20 link N-linked 0:7 arg1 Glycosylation 9:21 N-linked Glycosylation 0:21 N-linked Glycosylation on the N-terminus of the dopamine D2 and D3 receptors 0:75 N-linked Glycosylation on the N-terminus of the dopamine D2 and D3 receptors determines receptor association with specific microdomains in the plasma membrane. 25289757 5 21 theme surface 1021:1027 arg1 expression 1029:1038 proper cell surface expression 1009:1038 proper cell surface expression 1009:1038 Our results demonstrate that glycosylation on the N-terminus of the D₃ receptor is involved in the development of desensitization and proper cell surface expression. 25289757 3 22 theme underlying 432:441 arg1 principles 443:452 the underlying principles 428:452 the underlying principles governing the functional roles of glycosylation 428:500 In this study, we used the dopamine D₂and D₃receptors as an experimental model to understand the underlying principles governing the functional roles of glycosylation. 25289757 2 23 theme glycosylation 272:284 arg1 roles 263:267 The regulatory roles 248:267 The regulatory roles of glycosylation on receptor function 248:305 The regulatory roles of glycosylation on receptor function vary across receptor types. 25289757 1 24 theme protein-coupled 171:185 arg1 receptors 187:195 Numerous G protein-coupled receptors 160:195 Numerous G protein-coupled receptors (GPCRs) 160:203 Numerous G protein-coupled receptors (GPCRs) are glycosylated at extracellular regions. 25289757 1 24 theme protein-coupled 171:185 arg1 GPCRs 198:202 GPCRs 198:202 GPCRs 198:202 Numerous G protein-coupled receptors (GPCRs) are glycosylated at extracellular regions. 25289757 1 25 gly glycosylated 209:220 arg1 receptors 187:195 Numerous G protein-coupled receptors 160:195 Numerous G protein-coupled receptors (GPCRs) 160:203 Numerous G protein-coupled receptors (GPCRs) are glycosylated at extracellular regions. 25289757 1 25 gly glycosylated 209:220 arg1 GPCRs 198:202 GPCRs 198:202 GPCRs 198:202 Numerous G protein-coupled receptors (GPCRs) are glycosylated at extracellular regions. 25289757 1 25 gly glycosylated 209:220 arg2 regions 239:245 extracellular regions 225:245 extracellular regions 225:245 Numerous G protein-coupled receptors (GPCRs) are glycosylated at extracellular regions. 25289757 0 26 with association 97:107 arg1 microdomains 123:134 specific microdomains 114:134 specific microdomains in the plasma membrane 114:157 N-linked Glycosylation on the N-terminus of the dopamine D2 and D3 receptors determines receptor association with specific microdomains in the plasma membrane. 25289757 7 27 theme first 1337:1341 arg1 time 1343:1346 the first time 1333:1346 the first time 1333:1346 In conclusion, this study shows for the first time that glycosylation on the N-terminus of GPCRs is involved in endocytic pathway selection through specific microdomains. 25289757 6 28 theme D₃receptors 1124:1134 arg1 internalization 1099:1113 the internalization 1095:1113 the internalization of D₂and D₃receptors 1095:1134 In addition, glycosylation on the N-terminus mediates the internalization of D₂and D₃receptors within the caveolae and clathrin-coated pit microdomains of the plasma membrane, respectively, by regulating receptor interactions with caveolin-1 and clathrin. 25289757 0 29 theme N-linked 0:7 arg1 Glycosylation 9:21 N-linked Glycosylation 0:21 N-linked Glycosylation on the N-terminus of the dopamine D2 and D3 receptors 0:75 N-linked Glycosylation on the N-terminus of the dopamine D2 and D3 receptors determines receptor association with specific microdomains in the plasma membrane. 25289757 3 30 used used 353:356 arg2 we 350:351 we 350:351 we 350:351 In this study, we used the dopamine D₂and D₃receptors as an experimental model to understand the underlying principles governing the functional roles of glycosylation. 25289757 2 31 theme receptor 319:326 arg1 types 328:332 receptor types 319:332 receptor types 319:332 The regulatory roles of glycosylation on receptor function vary across receptor types. 25289757 6 32 from glycosylation 1054:1066 arg1 N-terminus 1075:1084 the N-terminus 1071:1084 the N-terminus 1071:1084 In addition, glycosylation on the N-terminus mediates the internalization of D₂and D₃receptors within the caveolae and clathrin-coated pit microdomains of the plasma membrane, respectively, by regulating receptor interactions with caveolin-1 and clathrin. 25289757 3 33 theme dopamine 362:369 arg1 D₃receptors 377:387 the dopamine D₂and D₃receptors 358:387 the dopamine D₂and D₃receptors 358:387 In this study, we used the dopamine D₂and D₃receptors as an experimental model to understand the underlying principles governing the functional roles of glycosylation. 25289757 3 33 theme dopamine 362:369 arg1 model 408:412 an experimental model 392:412 an experimental model 392:412 In this study, we used the dopamine D₂and D₃receptors as an experimental model to understand the underlying principles governing the functional roles of glycosylation. 25289757 4 34 theme receptor 758:765 arg1 signaling 813:821 signaling 813:821 signaling 813:821 We used the pharmacological inhibitor, tunicamycin, to inhibit glycosylation, generated chimeric D₂and D₃receptors by swapping their respective N-termini, and produced the glycosylation site mutant D₂and D₃receptors to study the roles of glycosylation on receptor functions, including cell surface expression, signaling, and internalization through specific microdomains. 25289757 4 34 theme receptor 758:765 arg1 internalization 828:842 internalization 828:842 internalization 828:842 We used the pharmacological inhibitor, tunicamycin, to inhibit glycosylation, generated chimeric D₂and D₃receptors by swapping their respective N-termini, and produced the glycosylation site mutant D₂and D₃receptors to study the roles of glycosylation on receptor functions, including cell surface expression, signaling, and internalization through specific microdomains. 25289757 4 34 theme receptor 758:765 arg1 expression 801:810 cell surface expression 788:810 cell surface expression 788:810 We used the pharmacological inhibitor, tunicamycin, to inhibit glycosylation, generated chimeric D₂and D₃receptors by swapping their respective N-termini, and produced the glycosylation site mutant D₂and D₃receptors to study the roles of glycosylation on receptor functions, including cell surface expression, signaling, and internalization through specific microdomains. 25289757 4 34 theme receptor 758:765 arg1 functions 767:775 receptor functions 758:775 receptor functions 758:775 We used the pharmacological inhibitor, tunicamycin, to inhibit glycosylation, generated chimeric D₂and D₃receptors by swapping their respective N-termini, and produced the glycosylation site mutant D₂and D₃receptors to study the roles of glycosylation on receptor functions, including cell surface expression, signaling, and internalization through specific microdomains. 25289757 5 35 theme desensitization 989:1003 arg1 development 974:984 the development 970:984 the development of desensitization and proper cell surface expression 970:1038 Our results demonstrate that glycosylation on the N-terminus of the D₃ receptor is involved in the development of desensitization and proper cell surface expression. 25289757 3 36 theme functional 468:477 arg1 roles 479:483 the functional roles 464:483 the functional roles of glycosylation 464:500 In this study, we used the dopamine D₂and D₃receptors as an experimental model to understand the underlying principles governing the functional roles of glycosylation. 25289757 3 37 theme D₂and 371:375 arg1 D₃receptors 377:387 the dopamine D₂and D₃receptors 358:387 the dopamine D₂and D₃receptors 358:387 In this study, we used the dopamine D₂and D₃receptors as an experimental model to understand the underlying principles governing the functional roles of glycosylation. 25289757 3 37 theme D₂and 371:375 arg1 model 408:412 an experimental model 392:412 an experimental model 392:412 In this study, we used the dopamine D₂and D₃receptors as an experimental model to understand the underlying principles governing the functional roles of glycosylation. 25289757 6 38 with interactions 1254:1265 arg1 clathrin 1287:1294 clathrin 1287:1294 clathrin 1287:1294 In addition, glycosylation on the N-terminus mediates the internalization of D₂and D₃receptors within the caveolae and clathrin-coated pit microdomains of the plasma membrane, respectively, by regulating receptor interactions with caveolin-1 and clathrin. 25289757 6 38 with interactions 1254:1265 arg1 caveolin-1 1272:1281 caveolin-1 1272:1281 caveolin-1 1272:1281 In addition, glycosylation on the N-terminus mediates the internalization of D₂and D₃receptors within the caveolae and clathrin-coated pit microdomains of the plasma membrane, respectively, by regulating receptor interactions with caveolin-1 and clathrin. 25289757 0 39 theme specific 114:121 arg1 microdomains 123:134 specific microdomains 114:134 specific microdomains in the plasma membrane 114:157 N-linked Glycosylation on the N-terminus of the dopamine D2 and D3 receptors determines receptor association with specific microdomains in the plasma membrane. 25289757 5 40 theme receptor 946:953 arg1 N-terminus 925:934 the N-terminus 921:934 the N-terminus of the D₃ receptor 921:953 Our results demonstrate that glycosylation on the N-terminus of the D₃ receptor is involved in the development of desensitization and proper cell surface expression. 25289757 8 41 theme cellular 1507:1514 arg1 environment 1516:1526 the cellular environment 1503:1526 the cellular environment that influence posttranslational modification 1503:1572 These data suggest that changes in the cellular environment that influence posttranslational modification could be an important determinant of intracellular GPCR trafficking. 25289757 4 42 theme specific 852:859 arg1 microdomains 861:872 specific microdomains 852:872 specific microdomains 852:872 We used the pharmacological inhibitor, tunicamycin, to inhibit glycosylation, generated chimeric D₂and D₃receptors by swapping their respective N-termini, and produced the glycosylation site mutant D₂and D₃receptors to study the roles of glycosylation on receptor functions, including cell surface expression, signaling, and internalization through specific microdomains. 25289757 2 43 from roles 263:267 arg1 function 298:305 receptor function 289:305 receptor function 289:305 The regulatory roles of glycosylation on receptor function vary across receptor types. 25289757 7 44 gly glycosylation 1353:1365 arg1 N-terminus 1374:1383 the N-terminus 1370:1383 the N-terminus of GPCRs 1370:1392 In conclusion, this study shows for the first time that glycosylation on the N-terminus of GPCRs is involved in endocytic pathway selection through specific microdomains. 25289757 7 44 gly glycosylation 1353:1365 arg1 selection 1427:1435 endocytic pathway selection 1409:1435 endocytic pathway selection through specific microdomains 1409:1465 In conclusion, this study shows for the first time that glycosylation on the N-terminus of GPCRs is involved in endocytic pathway selection through specific microdomains. 25289757 4 45 theme site 689:692 arg1 mutant 694:699 the glycosylation site mutant 671:699 the glycosylation site mutant D₂and D₃receptors to study the roles of glycosylation on receptor functions, including cell surface expression, signaling, and internalization through specific microdomains 671:872 We used the pharmacological inhibitor, tunicamycin, to inhibit glycosylation, generated chimeric D₂and D₃receptors by swapping their respective N-termini, and produced the glycosylation site mutant D₂and D₃receptors to study the roles of glycosylation on receptor functions, including cell surface expression, signaling, and internalization through specific microdomains. 25289757 8 46 theme posttranslational 1543:1559 arg1 modification 1561:1572 posttranslational modification 1543:1572 posttranslational modification 1543:1572 These data suggest that changes in the cellular environment that influence posttranslational modification could be an important determinant of intracellular GPCR trafficking. 25289757 4 47 used used 506:509 arg2 We 503:504 We 503:504 We 503:504 We used the pharmacological inhibitor, tunicamycin, to inhibit glycosylation, generated chimeric D₂and D₃receptors by swapping their respective N-termini, and produced the glycosylation site mutant D₂and D₃receptors to study the roles of glycosylation on receptor functions, including cell surface expression, signaling, and internalization through specific microdomains. 25289757 7 48 from glycosylation 1353:1365 arg1 N-terminus 1374:1383 the N-terminus 1370:1383 the N-terminus of GPCRs 1370:1392 In conclusion, this study shows for the first time that glycosylation on the N-terminus of GPCRs is involved in endocytic pathway selection through specific microdomains. 25289757 0 49 theme dopamine 48:55 arg1 D2 57:58 dopamine D2 48:58 dopamine D2 48:58 N-linked Glycosylation on the N-terminus of the dopamine D2 and D3 receptors determines receptor association with specific microdomains in the plasma membrane. 25289757 5 50 theme cell 1016:1019 arg1 expression 1029:1038 proper cell surface expression 1009:1038 proper cell surface expression 1009:1038 Our results demonstrate that glycosylation on the N-terminus of the D₃ receptor is involved in the development of desensitization and proper cell surface expression. 25289757 6 51 theme plasma 1200:1205 arg1 membrane 1207:1214 the plasma membrane 1196:1214 the plasma membrane 1196:1214 In addition, glycosylation on the N-terminus mediates the internalization of D₂and D₃receptors within the caveolae and clathrin-coated pit microdomains of the plasma membrane, respectively, by regulating receptor interactions with caveolin-1 and clathrin. 25289757 3 52 theme experimental 395:406 arg1 D₃receptors 377:387 the dopamine D₂and D₃receptors 358:387 the dopamine D₂and D₃receptors 358:387 In this study, we used the dopamine D₂and D₃receptors as an experimental model to understand the underlying principles governing the functional roles of glycosylation. 25289757 3 52 theme experimental 395:406 arg1 model 408:412 an experimental model 392:412 an experimental model 392:412 In this study, we used the dopamine D₂and D₃receptors as an experimental model to understand the underlying principles governing the functional roles of glycosylation. 25289757 6 53 theme receptor 1245:1252 arg1 interactions 1254:1265 receptor interactions 1245:1265 receptor interactions with caveolin-1 and clathrin 1245:1294 In addition, glycosylation on the N-terminus mediates the internalization of D₂and D₃receptors within the caveolae and clathrin-coated pit microdomains of the plasma membrane, respectively, by regulating receptor interactions with caveolin-1 and clathrin. 25289757 0 54 theme plasma 143:148 arg1 membrane 150:157 the plasma membrane 139:157 the plasma membrane 139:157 N-linked Glycosylation on the N-terminus of the dopamine D2 and D3 receptors determines receptor association with specific microdomains in the plasma membrane. 25289757 7 55 theme specific 1445:1452 arg1 microdomains 1454:1465 specific microdomains 1445:1465 specific microdomains 1445:1465 In conclusion, this study shows for the first time that glycosylation on the N-terminus of GPCRs is involved in endocytic pathway selection through specific microdomains. 25289757 7 56 theme pathway 1419:1425 arg1 selection 1427:1435 endocytic pathway selection 1409:1435 endocytic pathway selection through specific microdomains 1409:1465 In conclusion, this study shows for the first time that glycosylation on the N-terminus of GPCRs is involved in endocytic pathway selection through specific microdomains. 25289757 6 57 gly glycosylation 1054:1066 arg1 N-terminus 1075:1084 the N-terminus 1071:1084 the N-terminus 1071:1084 In addition, glycosylation on the N-terminus mediates the internalization of D₂and D₃receptors within the caveolae and clathrin-coated pit microdomains of the plasma membrane, respectively, by regulating receptor interactions with caveolin-1 and clathrin. 25289757 5 58 theme expression 1029:1038 arg1 development 974:984 the development 970:984 the development of desensitization and proper cell surface expression 970:1038 Our results demonstrate that glycosylation on the N-terminus of the D₃ receptor is involved in the development of desensitization and proper cell surface expression. 25289757 5 59 theme proper 1009:1014 arg1 expression 1029:1038 proper cell surface expression 1009:1038 proper cell surface expression 1009:1038 Our results demonstrate that glycosylation on the N-terminus of the D₃ receptor is involved in the development of desensitization and proper cell surface expression. 25289757 8 60 theme important 1586:1594 arg1 determinant 1596:1606 an important determinant 1583:1606 an important determinant of intracellular GPCR trafficking 1583:1640 These data suggest that changes in the cellular environment that influence posttranslational modification could be an important determinant of intracellular GPCR trafficking. 25289757 8 60 theme important 1586:1594 arg1 changes 1492:1498 changes 1492:1498 changes in the cellular environment that influence posttranslational modification 1492:1572 These data suggest that changes in the cellular environment that influence posttranslational modification could be an important determinant of intracellular GPCR trafficking. 25289757 3 61 theme glycosylation 488:500 arg1 roles 479:483 the functional roles 464:483 the functional roles of glycosylation 464:500 In this study, we used the dopamine D₂and D₃receptors as an experimental model to understand the underlying principles governing the functional roles of glycosylation. 25289757 1 62 theme extracellular 225:237 arg1 regions 239:245 extracellular regions 225:245 extracellular regions 225:245 Numerous G protein-coupled receptors (GPCRs) are glycosylated at extracellular regions. 25289757 8 63 theme intracellular 1611:1623 arg1 trafficking 1630:1640 intracellular GPCR trafficking 1611:1640 intracellular GPCR trafficking 1611:1640 These data suggest that changes in the cellular environment that influence posttranslational modification could be an important determinant of intracellular GPCR trafficking. 25289757 2 64 theme regulatory 252:261 arg1 roles 263:267 The regulatory roles 248:267 The regulatory roles of glycosylation on receptor function 248:305 The regulatory roles of glycosylation on receptor function vary across receptor types. 25289757 6 65 theme pit 1176:1178 arg1 membrane 1207:1214 the plasma membrane 1196:1214 the plasma membrane 1196:1214 In addition, glycosylation on the N-terminus mediates the internalization of D₂and D₃receptors within the caveolae and clathrin-coated pit microdomains of the plasma membrane, respectively, by regulating receptor interactions with caveolin-1 and clathrin. 25289757 6 65 theme pit 1176:1178 arg1 microdomains 1180:1191 the caveolae and clathrin-coated pit microdomains 1143:1191 microdomains 1180:1191 In addition, glycosylation on the N-terminus mediates the internalization of D₂and D₃receptors within the caveolae and clathrin-coated pit microdomains of the plasma membrane, respectively, by regulating receptor interactions with caveolin-1 and clathrin. 25289757 4 66 theme glycosylation 675:687 arg1 mutant 694:699 the glycosylation site mutant 671:699 the glycosylation site mutant D₂and D₃receptors to study the roles of glycosylation on receptor functions, including cell surface expression, signaling, and internalization through specific microdomains 671:872 We used the pharmacological inhibitor, tunicamycin, to inhibit glycosylation, generated chimeric D₂and D₃receptors by swapping their respective N-termini, and produced the glycosylation site mutant D₂and D₃receptors to study the roles of glycosylation on receptor functions, including cell surface expression, signaling, and internalization through specific microdomains. 25289757 0 67 from microdomains 123:134 arg1 membrane 150:157 the plasma membrane 139:157 the plasma membrane 139:157 N-linked Glycosylation on the N-terminus of the dopamine D2 and D3 receptors determines receptor association with specific microdomains in the plasma membrane. 25289757 0 68 theme D2 57:58 arg1 receptors 67:75 the dopamine D2 and D3 receptors 44:75 the dopamine D2 and D3 receptors 44:75 N-linked Glycosylation on the N-terminus of the dopamine D2 and D3 receptors determines receptor association with specific microdomains in the plasma membrane. 25289757 7 69 theme endocytic 1409:1417 arg1 selection 1427:1435 endocytic pathway selection 1409:1435 endocytic pathway selection through specific microdomains 1409:1465 In conclusion, this study shows for the first time that glycosylation on the N-terminus of GPCRs is involved in endocytic pathway selection through specific microdomains. 25289757 5 70 from glycosylation 904:916 arg1 N-terminus 925:934 the N-terminus 921:934 the N-terminus of the D₃ receptor 921:953 Our results demonstrate that glycosylation on the N-terminus of the D₃ receptor is involved in the development of desensitization and proper cell surface expression. 25289757 6 71 theme clathrin-coated 1160:1174 arg1 membrane 1207:1214 the plasma membrane 1196:1214 the plasma membrane 1196:1214 In addition, glycosylation on the N-terminus mediates the internalization of D₂and D₃receptors within the caveolae and clathrin-coated pit microdomains of the plasma membrane, respectively, by regulating receptor interactions with caveolin-1 and clathrin. 25289757 6 71 theme clathrin-coated 1160:1174 arg1 microdomains 1180:1191 the caveolae and clathrin-coated pit microdomains 1143:1191 microdomains 1180:1191 In addition, glycosylation on the N-terminus mediates the internalization of D₂and D₃receptors within the caveolae and clathrin-coated pit microdomains of the plasma membrane, respectively, by regulating receptor interactions with caveolin-1 and clathrin. 25289757 8 72 from changes 1492:1498 arg1 environment 1516:1526 the cellular environment 1503:1526 the cellular environment that influence posttranslational modification 1503:1572 These data suggest that changes in the cellular environment that influence posttranslational modification could be an important determinant of intracellular GPCR trafficking. 25289757 4 73 theme respective 636:645 arg1 N-termini 647:655 their respective N-termini 630:655 their respective N-termini 630:655 We used the pharmacological inhibitor, tunicamycin, to inhibit glycosylation, generated chimeric D₂and D₃receptors by swapping their respective N-termini, and produced the glycosylation site mutant D₂and D₃receptors to study the roles of glycosylation on receptor functions, including cell surface expression, signaling, and internalization through specific microdomains. 24280219 10 0 theme lipid-packing 1487:1499 arg1 motif 1515:1519 an amphipathic lipid-packing sensor (ALPS) motif 1472:1519 an amphipathic lipid-packing sensor (ALPS) motif 1472:1519 Thr-87 is located within an amphipathic lipid-packing sensor (ALPS) motif, which participates in targeting of synapsin I to synapses by contributing to the binding of synapsin I to SVs. 24280219 5 1 theme memory 637:642 arg1 deficits 644:651 memory deficits 637:651 memory deficits 637:651 Disruption of synapsin I function results in reduced size of the RPSV, increased synaptic depression, memory deficits, and epilepsy. 24280219 9 2 theme synapsin 1371:1378 arg1 O-GlcNAcylation 1352:1366 O-GlcNAcylation 1352:1366 O-GlcNAcylation of synapsin I at Thr-87 1352:1390 All O-GlcNAc sites mapped within the regulatory regions on synapsin I. Expression of synapsin I where a single O-GlcNAc site Thr-87 was mutated to alanine in primary hippocampal neurons dramatically increased localization of synapsin I to synapses, increased density of SV clusters along axons, and the size of the RPSV, suggesting that O-GlcNAcylation of synapsin I at Thr-87 may be a mechanism to modulate presynaptic plasticity. 24280219 9 2 theme synapsin 1371:1378 arg1 mechanism 1401:1409 a mechanism to modulate presynaptic plasticity 1399:1444 a mechanism to modulate presynaptic plasticity 1399:1444 All O-GlcNAc sites mapped within the regulatory regions on synapsin I. Expression of synapsin I where a single O-GlcNAc site Thr-87 was mutated to alanine in primary hippocampal neurons dramatically increased localization of synapsin I to synapses, increased density of SV clusters along axons, and the size of the RPSV, suggesting that O-GlcNAcylation of synapsin I at Thr-87 may be a mechanism to modulate presynaptic plasticity. 24280219 8 3 theme known 940:944 arg1 sites 1008:1012 known Ca(2+)/calmodulin-dependent protein kinase II phosphorylation sites 940:1012 known Ca(2+)/calmodulin-dependent protein kinase II phosphorylation sites 940:1012 We identified three novel O-GlcNAc sites on synapsin I, two of which are known Ca(2+)/calmodulin-dependent protein kinase II phosphorylation sites. 24280219 8 3 theme known 940:944 arg1 two 923:925 two 923:925 two 923:925 We identified three novel O-GlcNAc sites on synapsin I, two of which are known Ca(2+)/calmodulin-dependent protein kinase II phosphorylation sites. 24280219 8 3 theme known 940:944 arg1 sites 902:906 three novel O-GlcNAc sites 881:906 three novel O-GlcNAc sites 881:906 We identified three novel O-GlcNAc sites on synapsin I, two of which are known Ca(2+)/calmodulin-dependent protein kinase II phosphorylation sites. 24280219 2 4 theme presynaptic 289:299 arg1 plasticity 301:310 hippocampal presynaptic plasticity 277:310 hippocampal presynaptic plasticity 277:310 Our previous findings implicated O-GlcNAc in hippocampal presynaptic plasticity. 24280219 0 5 link O-linked 0:7 arg1 thr-87 47:52 O-linked β-N-acetylglucosamine (O-GlcNAc) site thr-87 0:52 O-linked β-N-acetylglucosamine (O-GlcNAc) site thr-87 0:52 O-linked β-N-acetylglucosamine (O-GlcNAc) site thr-87 regulates synapsin I localization to synapses and size of the reserve pool of synaptic vesicles. 24280219 5 6 theme increased 606:614 arg1 depression 625:634 increased synaptic depression 606:634 increased synaptic depression 606:634 Disruption of synapsin I function results in reduced size of the RPSV, increased synaptic depression, memory deficits, and epilepsy. 24280219 7 7 theme hippocampal 828:838 arg1 synaptogenesis 840:853 hippocampal synaptogenesis 828:853 hippocampal synaptogenesis in the rat 828:864 We found that synapsin I is modified by O-GlcNAc during hippocampal synaptogenesis in the rat. 24280219 9 8 theme primary 1173:1179 arg1 neurons 1193:1199 primary hippocampal neurons 1173:1199 primary hippocampal neurons 1173:1199 All O-GlcNAc sites mapped within the regulatory regions on synapsin I. Expression of synapsin I where a single O-GlcNAc site Thr-87 was mutated to alanine in primary hippocampal neurons dramatically increased localization of synapsin I to synapses, increased density of SV clusters along axons, and the size of the RPSV, suggesting that O-GlcNAcylation of synapsin I at Thr-87 may be a mechanism to modulate presynaptic plasticity. 24280219 8 9 theme protein 974:980 arg1 kinase 982:987 Ca(2+)/calmodulin-dependent protein kinase II 946:990 known Ca(2+)/calmodulin-dependent protein kinase II phosphorylation sites 940:1012 We identified three novel O-GlcNAc sites on synapsin I, two of which are known Ca(2+)/calmodulin-dependent protein kinase II phosphorylation sites. 24280219 11 10 theme ALPS 1722:1725 arg1 motif 1727:1731 the ALPS motif 1718:1731 the ALPS motif 1718:1731 We discuss the possibility that O-GlcNAcylation of Thr-87 interferes with folding of the ALPS motif, providing a means for regulating the association of synapsin I with SVs as a mechanism contributing to synapsin I localization and RPSV generation. 24280219 4 11 theme synapsin 455:462 arg1 association 440:450 Dynamic association 432:450 Dynamic association of synapsin I with synaptic vesicles (SVs) 432:493 Dynamic association of synapsin I with synaptic vesicles (SVs) regulates the size and release of RPSV. 24280219 0 12 theme pool 124:127 arg1 size 104:107 size 104:107 size 104:107 O-linked β-N-acetylglucosamine (O-GlcNAc) site thr-87 regulates synapsin I localization to synapses and size of the reserve pool of synaptic vesicles. 24280219 0 12 theme pool 124:127 arg1 synapses 91:98 synapses 91:98 synapses 91:98 O-linked β-N-acetylglucosamine (O-GlcNAc) site thr-87 regulates synapsin I localization to synapses and size of the reserve pool of synaptic vesicles. 24280219 9 13 theme presynaptic 1423:1433 arg1 plasticity 1435:1444 presynaptic plasticity 1423:1444 presynaptic plasticity 1423:1444 All O-GlcNAc sites mapped within the regulatory regions on synapsin I. Expression of synapsin I where a single O-GlcNAc site Thr-87 was mutated to alanine in primary hippocampal neurons dramatically increased localization of synapsin I to synapses, increased density of SV clusters along axons, and the size of the RPSV, suggesting that O-GlcNAcylation of synapsin I at Thr-87 may be a mechanism to modulate presynaptic plasticity. 24280219 3 14 theme important 316:324 arg1 establishment 369:381 the establishment 365:381 the establishment of the reserve pool of synaptic vesicles (RPSV) 365:429 An important mechanism in presynaptic plasticity is the establishment of the reserve pool of synaptic vesicles (RPSV). 24280219 3 14 theme important 316:324 arg1 mechanism 326:334 An important mechanism 313:334 An important mechanism in presynaptic plasticity 313:360 An important mechanism in presynaptic plasticity is the establishment of the reserve pool of synaptic vesicles (RPSV). 24280219 10 15 theme synapsin 1557:1564 arg1 targeting 1544:1552 targeting 1544:1552 targeting of synapsin I to synapses 1544:1578 Thr-87 is located within an amphipathic lipid-packing sensor (ALPS) motif, which participates in targeting of synapsin I to synapses by contributing to the binding of synapsin I to SVs. 24280219 0 16 theme synaptic 132:139 arg1 vesicles 141:148 synaptic vesicles 132:148 synaptic vesicles 132:148 O-linked β-N-acetylglucosamine (O-GlcNAc) site thr-87 regulates synapsin I localization to synapses and size of the reserve pool of synaptic vesicles. 24280219 1 17 located found 191:195 arg2 O-GlcNAc 151:158 O-GlcNAc 151:158 O-GlcNAc 151:158 O-GlcNAc is a carbohydrate modification found on cytosolic and nuclear proteins. 24280219 1 17 located found 191:195 arg2 modification 178:189 a carbohydrate modification 163:189 a carbohydrate modification found on cytosolic and nuclear proteins 163:229 O-GlcNAc is a carbohydrate modification found on cytosolic and nuclear proteins. 24280219 1 17 located found 191:195 arg1 proteins 222:229 cytosolic and nuclear proteins 200:229 cytosolic and nuclear proteins 200:229 O-GlcNAc is a carbohydrate modification found on cytosolic and nuclear proteins. 24280219 5 18 theme synapsin 549:556 arg1 function 560:567 synapsin I function 549:567 synapsin I function 549:567 Disruption of synapsin I function results in reduced size of the RPSV, increased synaptic depression, memory deficits, and epilepsy. 24280219 8 19 from sites 902:906 arg1 synapsin 911:918 synapsin I 911:920 synapsin I 911:920 We identified three novel O-GlcNAc sites on synapsin I, two of which are known Ca(2+)/calmodulin-dependent protein kinase II phosphorylation sites. 24280219 10 20 located located 1457:1463 arg1 motif 1515:1519 an amphipathic lipid-packing sensor (ALPS) motif 1472:1519 an amphipathic lipid-packing sensor (ALPS) motif 1472:1519 Thr-87 is located within an amphipathic lipid-packing sensor (ALPS) motif, which participates in targeting of synapsin I to synapses by contributing to the binding of synapsin I to SVs. 24280219 10 20 located located 1457:1463 arg2 Thr-87 1447:1452 Thr-87 1447:1452 Thr-87 1447:1452 Thr-87 is located within an amphipathic lipid-packing sensor (ALPS) motif, which participates in targeting of synapsin I to synapses by contributing to the binding of synapsin I to SVs. 24280219 11 21 theme Thr-87 1684:1689 arg1 O-GlcNAcylation 1665:1679 O-GlcNAcylation 1665:1679 O-GlcNAcylation of Thr-87 1665:1689 We discuss the possibility that O-GlcNAcylation of Thr-87 interferes with folding of the ALPS motif, providing a means for regulating the association of synapsin I with SVs as a mechanism contributing to synapsin I localization and RPSV generation. 24280219 9 22 from alanine 1162:1168 arg1 neurons 1193:1199 primary hippocampal neurons 1173:1199 primary hippocampal neurons 1173:1199 All O-GlcNAc sites mapped within the regulatory regions on synapsin I. Expression of synapsin I where a single O-GlcNAc site Thr-87 was mutated to alanine in primary hippocampal neurons dramatically increased localization of synapsin I to synapses, increased density of SV clusters along axons, and the size of the RPSV, suggesting that O-GlcNAcylation of synapsin I at Thr-87 may be a mechanism to modulate presynaptic plasticity. 24280219 0 23 theme synapsin 64:71 arg1 localization 75:86 synapsin I localization 64:86 synapsin I localization to synapses and size of the reserve pool of synaptic vesicles 64:148 O-linked β-N-acetylglucosamine (O-GlcNAc) site thr-87 regulates synapsin I localization to synapses and size of the reserve pool of synaptic vesicles. 24280219 2 24 theme previous 236:243 arg1 findings 245:252 Our previous findings 232:252 Our previous findings 232:252 Our previous findings implicated O-GlcNAc in hippocampal presynaptic plasticity. 24280219 9 25 theme O-GlcNAc 1019:1026 arg1 sites 1028:1032 All O-GlcNAc sites 1015:1032 All O-GlcNAc sites mapped within the regulatory regions on synapsin I. Expression of synapsin I where a single O-GlcNAc site Thr-87 was mutated to alanine in primary hippocampal neurons 1015:1199 All O-GlcNAc sites mapped within the regulatory regions on synapsin I. Expression of synapsin I where a single O-GlcNAc site Thr-87 was mutated to alanine in primary hippocampal neurons dramatically increased localization of synapsin I to synapses, increased density of SV clusters along axons, and the size of the RPSV, suggesting that O-GlcNAcylation of synapsin I at Thr-87 may be a mechanism to modulate presynaptic plasticity. 24280219 9 26 theme increased 1264:1272 arg1 density 1274:1280 increased density 1264:1280 increased density of SV clusters along axons 1264:1307 All O-GlcNAc sites mapped within the regulatory regions on synapsin I. Expression of synapsin I where a single O-GlcNAc site Thr-87 was mutated to alanine in primary hippocampal neurons dramatically increased localization of synapsin I to synapses, increased density of SV clusters along axons, and the size of the RPSV, suggesting that O-GlcNAcylation of synapsin I at Thr-87 may be a mechanism to modulate presynaptic plasticity. 24280219 10 27 theme synapsin 1614:1621 arg1 binding 1603:1609 the binding 1599:1609 the binding of synapsin I to SVs 1599:1630 Thr-87 is located within an amphipathic lipid-packing sensor (ALPS) motif, which participates in targeting of synapsin I to synapses by contributing to the binding of synapsin I to SVs. 24280219 9 28 theme clusters 1288:1295 arg1 synapses 1254:1261 synapses 1254:1261 synapses 1254:1261 All O-GlcNAc sites mapped within the regulatory regions on synapsin I. Expression of synapsin I where a single O-GlcNAc site Thr-87 was mutated to alanine in primary hippocampal neurons dramatically increased localization of synapsin I to synapses, increased density of SV clusters along axons, and the size of the RPSV, suggesting that O-GlcNAcylation of synapsin I at Thr-87 may be a mechanism to modulate presynaptic plasticity. 24280219 9 28 theme clusters 1288:1295 arg1 density 1274:1280 increased density 1264:1280 increased density of SV clusters along axons 1264:1307 All O-GlcNAc sites mapped within the regulatory regions on synapsin I. Expression of synapsin I where a single O-GlcNAc site Thr-87 was mutated to alanine in primary hippocampal neurons dramatically increased localization of synapsin I to synapses, increased density of SV clusters along axons, and the size of the RPSV, suggesting that O-GlcNAcylation of synapsin I at Thr-87 may be a mechanism to modulate presynaptic plasticity. 24280219 9 28 theme clusters 1288:1295 arg1 size 1318:1321 the size 1314:1321 the size of the RPSV 1314:1333 All O-GlcNAc sites mapped within the regulatory regions on synapsin I. Expression of synapsin I where a single O-GlcNAc site Thr-87 was mutated to alanine in primary hippocampal neurons dramatically increased localization of synapsin I to synapses, increased density of SV clusters along axons, and the size of the RPSV, suggesting that O-GlcNAcylation of synapsin I at Thr-87 may be a mechanism to modulate presynaptic plasticity. 24280219 5 29 theme function 560:567 arg1 Disruption 535:544 Disruption 535:544 Disruption of synapsin I function 535:567 Disruption of synapsin I function results in reduced size of the RPSV, increased synaptic depression, memory deficits, and epilepsy. 24280219 0 30 theme O-linked 0:7 arg1 thr-87 47:52 O-linked β-N-acetylglucosamine (O-GlcNAc) site thr-87 0:52 O-linked β-N-acetylglucosamine (O-GlcNAc) site thr-87 0:52 O-linked β-N-acetylglucosamine (O-GlcNAc) site thr-87 regulates synapsin I localization to synapses and size of the reserve pool of synaptic vesicles. 24280219 8 31 theme novel 887:891 arg1 sites 902:906 three novel O-GlcNAc sites 881:906 three novel O-GlcNAc sites 881:906 We identified three novel O-GlcNAc sites on synapsin I, two of which are known Ca(2+)/calmodulin-dependent protein kinase II phosphorylation sites. 24280219 3 32 theme reserve 390:396 arg1 pool 398:401 the reserve pool 386:401 the reserve pool of synaptic vesicles (RPSV) 386:429 An important mechanism in presynaptic plasticity is the establishment of the reserve pool of synaptic vesicles (RPSV). 24280219 9 33 theme synapsin 1074:1081 arg1 Expression 1086:1095 synapsin I. Expression 1074:1095 synapsin I. Expression of synapsin I where a single O-GlcNAc site Thr-87 was mutated to alanine in primary hippocampal neurons 1074:1199 All O-GlcNAc sites mapped within the regulatory regions on synapsin I. Expression of synapsin I where a single O-GlcNAc site Thr-87 was mutated to alanine in primary hippocampal neurons dramatically increased localization of synapsin I to synapses, increased density of SV clusters along axons, and the size of the RPSV, suggesting that O-GlcNAcylation of synapsin I at Thr-87 may be a mechanism to modulate presynaptic plasticity. 24280219 8 34 theme sites 902:906 arg1 sites 1008:1012 known Ca(2+)/calmodulin-dependent protein kinase II phosphorylation sites 940:1012 known Ca(2+)/calmodulin-dependent protein kinase II phosphorylation sites 940:1012 We identified three novel O-GlcNAc sites on synapsin I, two of which are known Ca(2+)/calmodulin-dependent protein kinase II phosphorylation sites. 24280219 8 34 theme sites 902:906 arg1 two 923:925 two 923:925 two 923:925 We identified three novel O-GlcNAc sites on synapsin I, two of which are known Ca(2+)/calmodulin-dependent protein kinase II phosphorylation sites. 24280219 8 34 theme sites 902:906 arg1 sites 902:906 three novel O-GlcNAc sites 881:906 three novel O-GlcNAc sites 881:906 We identified three novel O-GlcNAc sites on synapsin I, two of which are known Ca(2+)/calmodulin-dependent protein kinase II phosphorylation sites. 24280219 11 35 theme synapsin 1837:1844 arg1 localization 1848:1859 synapsin I localization 1837:1859 synapsin I localization 1837:1859 We discuss the possibility that O-GlcNAcylation of Thr-87 interferes with folding of the ALPS motif, providing a means for regulating the association of synapsin I with SVs as a mechanism contributing to synapsin I localization and RPSV generation. 24280219 3 36 theme vesicles 415:422 arg1 pool 398:401 the reserve pool 386:401 the reserve pool of synaptic vesicles (RPSV) 386:429 An important mechanism in presynaptic plasticity is the establishment of the reserve pool of synaptic vesicles (RPSV). 24280219 10 37 theme amphipathic 1475:1485 arg1 motif 1515:1519 an amphipathic lipid-packing sensor (ALPS) motif 1472:1519 an amphipathic lipid-packing sensor (ALPS) motif 1472:1519 Thr-87 is located within an amphipathic lipid-packing sensor (ALPS) motif, which participates in targeting of synapsin I to synapses by contributing to the binding of synapsin I to SVs. 24280219 9 38 theme synapsin 1100:1107 arg1 Expression 1086:1095 synapsin I. Expression 1074:1095 synapsin I. Expression of synapsin I where a single O-GlcNAc site Thr-87 was mutated to alanine in primary hippocampal neurons 1074:1199 All O-GlcNAc sites mapped within the regulatory regions on synapsin I. Expression of synapsin I where a single O-GlcNAc site Thr-87 was mutated to alanine in primary hippocampal neurons dramatically increased localization of synapsin I to synapses, increased density of SV clusters along axons, and the size of the RPSV, suggesting that O-GlcNAcylation of synapsin I at Thr-87 may be a mechanism to modulate presynaptic plasticity. 24280219 11 39 with association 1771:1781 arg1 SVs 1802:1804 SVs 1802:1804 SVs 1802:1804 We discuss the possibility that O-GlcNAcylation of Thr-87 interferes with folding of the ALPS motif, providing a means for regulating the association of synapsin I with SVs as a mechanism contributing to synapsin I localization and RPSV generation. 24280219 4 40 theme RPSV 529:532 arg1 release 518:524 release 518:524 release 518:524 Dynamic association of synapsin I with synaptic vesicles (SVs) regulates the size and release of RPSV. 24280219 4 40 theme RPSV 529:532 arg1 size 509:512 size 509:512 size 509:512 Dynamic association of synapsin I with synaptic vesicles (SVs) regulates the size and release of RPSV. 24280219 6 41 theme I 734:734 arg1 function 736:743 synapsin I function 725:743 synapsin I function in presynaptic plasticity 725:769 Here, we investigate whether O-GlcNAc directly regulates synapsin I function in presynaptic plasticity. 24280219 1 42 theme nuclear 214:220 arg1 proteins 222:229 cytosolic and nuclear proteins 200:229 cytosolic and nuclear proteins 200:229 O-GlcNAc is a carbohydrate modification found on cytosolic and nuclear proteins. 24280219 10 43 theme ALPS 1509:1512 arg1 motif 1515:1519 an amphipathic lipid-packing sensor (ALPS) motif 1472:1519 an amphipathic lipid-packing sensor (ALPS) motif 1472:1519 Thr-87 is located within an amphipathic lipid-packing sensor (ALPS) motif, which participates in targeting of synapsin I to synapses by contributing to the binding of synapsin I to SVs. 24280219 9 44 theme single 1119:1124 arg1 site 1135:1138 a single O-GlcNAc site Thr-87 1117:1145 a single O-GlcNAc site Thr-87 1117:1145 All O-GlcNAc sites mapped within the regulatory regions on synapsin I. Expression of synapsin I where a single O-GlcNAc site Thr-87 was mutated to alanine in primary hippocampal neurons dramatically increased localization of synapsin I to synapses, increased density of SV clusters along axons, and the size of the RPSV, suggesting that O-GlcNAcylation of synapsin I at Thr-87 may be a mechanism to modulate presynaptic plasticity. 24280219 9 45 from Thr-87 1385:1390 arg1 O-GlcNAcylation 1352:1366 O-GlcNAcylation 1352:1366 O-GlcNAcylation of synapsin I at Thr-87 1352:1390 All O-GlcNAc sites mapped within the regulatory regions on synapsin I. Expression of synapsin I where a single O-GlcNAc site Thr-87 was mutated to alanine in primary hippocampal neurons dramatically increased localization of synapsin I to synapses, increased density of SV clusters along axons, and the size of the RPSV, suggesting that O-GlcNAcylation of synapsin I at Thr-87 may be a mechanism to modulate presynaptic plasticity. 24280219 9 45 from Thr-87 1385:1390 arg1 mechanism 1401:1409 a mechanism to modulate presynaptic plasticity 1399:1444 a mechanism to modulate presynaptic plasticity 1399:1444 All O-GlcNAc sites mapped within the regulatory regions on synapsin I. Expression of synapsin I where a single O-GlcNAc site Thr-87 was mutated to alanine in primary hippocampal neurons dramatically increased localization of synapsin I to synapses, increased density of SV clusters along axons, and the size of the RPSV, suggesting that O-GlcNAcylation of synapsin I at Thr-87 may be a mechanism to modulate presynaptic plasticity. 24280219 10 46 theme sensor 1501:1506 arg1 motif 1515:1519 an amphipathic lipid-packing sensor (ALPS) motif 1472:1519 an amphipathic lipid-packing sensor (ALPS) motif 1472:1519 Thr-87 is located within an amphipathic lipid-packing sensor (ALPS) motif, which participates in targeting of synapsin I to synapses by contributing to the binding of synapsin I to SVs. 24280219 8 47 theme Ca 946:947 arg1 kinase 982:987 Ca(2+)/calmodulin-dependent protein kinase II 946:990 known Ca(2+)/calmodulin-dependent protein kinase II phosphorylation sites 940:1012 We identified three novel O-GlcNAc sites on synapsin I, two of which are known Ca(2+)/calmodulin-dependent protein kinase II phosphorylation sites. 24280219 8 48 theme 2+ 949:950 arg1 kinase 982:987 Ca(2+)/calmodulin-dependent protein kinase II 946:990 known Ca(2+)/calmodulin-dependent protein kinase II phosphorylation sites 940:1012 We identified three novel O-GlcNAc sites on synapsin I, two of which are known Ca(2+)/calmodulin-dependent protein kinase II phosphorylation sites. 24280219 2 49 theme hippocampal 277:287 arg1 plasticity 301:310 hippocampal presynaptic plasticity 277:310 hippocampal presynaptic plasticity 277:310 Our previous findings implicated O-GlcNAc in hippocampal presynaptic plasticity. 24280219 8 50 theme /calmodulin-dependent 952:972 arg1 kinase 982:987 Ca(2+)/calmodulin-dependent protein kinase II 946:990 known Ca(2+)/calmodulin-dependent protein kinase II phosphorylation sites 940:1012 We identified three novel O-GlcNAc sites on synapsin I, two of which are known Ca(2+)/calmodulin-dependent protein kinase II phosphorylation sites. 24280219 5 51 theme synaptic 616:623 arg1 depression 625:634 increased synaptic depression 606:634 increased synaptic depression 606:634 Disruption of synapsin I function results in reduced size of the RPSV, increased synaptic depression, memory deficits, and epilepsy. 24280219 1 52 theme carbohydrate 165:176 arg1 modification 178:189 a carbohydrate modification 163:189 a carbohydrate modification found on cytosolic and nuclear proteins 163:229 O-GlcNAc is a carbohydrate modification found on cytosolic and nuclear proteins. 24280219 1 52 theme carbohydrate 165:176 arg1 O-GlcNAc 151:158 O-GlcNAc 151:158 O-GlcNAc 151:158 O-GlcNAc is a carbohydrate modification found on cytosolic and nuclear proteins. 24280219 8 53 theme kinase 982:987 arg1 sites 1008:1012 known Ca(2+)/calmodulin-dependent protein kinase II phosphorylation sites 940:1012 known Ca(2+)/calmodulin-dependent protein kinase II phosphorylation sites 940:1012 We identified three novel O-GlcNAc sites on synapsin I, two of which are known Ca(2+)/calmodulin-dependent protein kinase II phosphorylation sites. 24280219 8 53 theme kinase 982:987 arg1 two 923:925 two 923:925 two 923:925 We identified three novel O-GlcNAc sites on synapsin I, two of which are known Ca(2+)/calmodulin-dependent protein kinase II phosphorylation sites. 24280219 8 53 theme kinase 982:987 arg1 sites 902:906 three novel O-GlcNAc sites 881:906 three novel O-GlcNAc sites 881:906 We identified three novel O-GlcNAc sites on synapsin I, two of which are known Ca(2+)/calmodulin-dependent protein kinase II phosphorylation sites. 24280219 0 54 theme reserve 116:122 arg1 pool 124:127 the reserve pool 112:127 the reserve pool of synaptic vesicles 112:148 O-linked β-N-acetylglucosamine (O-GlcNAc) site thr-87 regulates synapsin I localization to synapses and size of the reserve pool of synaptic vesicles. 24280219 9 55 theme hippocampal 1181:1191 arg1 neurons 1193:1199 primary hippocampal neurons 1173:1199 primary hippocampal neurons 1173:1199 All O-GlcNAc sites mapped within the regulatory regions on synapsin I. Expression of synapsin I where a single O-GlcNAc site Thr-87 was mutated to alanine in primary hippocampal neurons dramatically increased localization of synapsin I to synapses, increased density of SV clusters along axons, and the size of the RPSV, suggesting that O-GlcNAcylation of synapsin I at Thr-87 may be a mechanism to modulate presynaptic plasticity. 24280219 11 56 theme motif 1727:1731 arg1 folding 1707:1713 folding 1707:1713 folding of the ALPS motif 1707:1731 We discuss the possibility that O-GlcNAcylation of Thr-87 interferes with folding of the ALPS motif, providing a means for regulating the association of synapsin I with SVs as a mechanism contributing to synapsin I localization and RPSV generation. 24280219 1 57 theme cytosolic 200:208 arg1 proteins 222:229 cytosolic and nuclear proteins 200:229 cytosolic and nuclear proteins 200:229 O-GlcNAc is a carbohydrate modification found on cytosolic and nuclear proteins. 24280219 4 58 theme synaptic 471:478 arg1 SVs 490:492 SVs 490:492 SVs 490:492 Dynamic association of synapsin I with synaptic vesicles (SVs) regulates the size and release of RPSV. 24280219 4 58 theme synaptic 471:478 arg1 vesicles 480:487 synaptic vesicles 471:487 synaptic vesicles (SVs) 471:493 Dynamic association of synapsin I with synaptic vesicles (SVs) regulates the size and release of RPSV. 24280219 0 59 theme vesicles 141:148 arg1 pool 124:127 the reserve pool 112:127 the reserve pool of synaptic vesicles 112:148 O-linked β-N-acetylglucosamine (O-GlcNAc) site thr-87 regulates synapsin I localization to synapses and size of the reserve pool of synaptic vesicles. 24280219 11 60 theme RPSV 1865:1868 arg1 generation 1870:1879 RPSV generation 1865:1879 RPSV generation 1865:1879 We discuss the possibility that O-GlcNAcylation of Thr-87 interferes with folding of the ALPS motif, providing a means for regulating the association of synapsin I with SVs as a mechanism contributing to synapsin I localization and RPSV generation. 24280219 4 61 theme Dynamic 432:438 arg1 association 440:450 Dynamic association 432:450 Dynamic association of synapsin I with synaptic vesicles (SVs) 432:493 Dynamic association of synapsin I with synaptic vesicles (SVs) regulates the size and release of RPSV. 24280219 9 62 theme synapsin 1240:1247 arg1 localization 1224:1235 localization 1224:1235 localization of synapsin I to synapses, increased density of SV clusters along axons, and the size of the RPSV 1224:1333 All O-GlcNAc sites mapped within the regulatory regions on synapsin I. Expression of synapsin I where a single O-GlcNAc site Thr-87 was mutated to alanine in primary hippocampal neurons dramatically increased localization of synapsin I to synapses, increased density of SV clusters along axons, and the size of the RPSV, suggesting that O-GlcNAcylation of synapsin I at Thr-87 may be a mechanism to modulate presynaptic plasticity. 24280219 5 63 theme I 558:558 arg1 function 560:567 synapsin I function 549:567 synapsin I function 549:567 Disruption of synapsin I function results in reduced size of the RPSV, increased synaptic depression, memory deficits, and epilepsy. 24280219 7 64 mod modified 800:807 arg1 synapsin 786:793 synapsin I 786:795 synapsin I 786:795 We found that synapsin I is modified by O-GlcNAc during hippocampal synaptogenesis in the rat. 24280219 7 64 mod modified 800:807 arg3 O-GlcNAc 812:819 O-GlcNAc 812:819 O-GlcNAc 812:819 We found that synapsin I is modified by O-GlcNAc during hippocampal synaptogenesis in the rat. 24280219 8 65 theme phosphorylation 992:1006 arg1 sites 1008:1012 known Ca(2+)/calmodulin-dependent protein kinase II phosphorylation sites 940:1012 known Ca(2+)/calmodulin-dependent protein kinase II phosphorylation sites 940:1012 We identified three novel O-GlcNAc sites on synapsin I, two of which are known Ca(2+)/calmodulin-dependent protein kinase II phosphorylation sites. 24280219 8 65 theme phosphorylation 992:1006 arg1 two 923:925 two 923:925 two 923:925 We identified three novel O-GlcNAc sites on synapsin I, two of which are known Ca(2+)/calmodulin-dependent protein kinase II phosphorylation sites. 24280219 8 65 theme phosphorylation 992:1006 arg1 sites 902:906 three novel O-GlcNAc sites 881:906 three novel O-GlcNAc sites 881:906 We identified three novel O-GlcNAc sites on synapsin I, two of which are known Ca(2+)/calmodulin-dependent protein kinase II phosphorylation sites. 24280219 3 66 theme presynaptic 339:349 arg1 plasticity 351:360 presynaptic plasticity 339:360 presynaptic plasticity 339:360 An important mechanism in presynaptic plasticity is the establishment of the reserve pool of synaptic vesicles (RPSV). 24280219 7 67 from synaptogenesis 840:853 arg1 rat 862:864 the rat 858:864 the rat 858:864 We found that synapsin I is modified by O-GlcNAc during hippocampal synaptogenesis in the rat. 24280219 9 68 theme SV 1285:1286 arg1 clusters 1288:1295 SV clusters 1285:1295 SV clusters 1285:1295 All O-GlcNAc sites mapped within the regulatory regions on synapsin I. Expression of synapsin I where a single O-GlcNAc site Thr-87 was mutated to alanine in primary hippocampal neurons dramatically increased localization of synapsin I to synapses, increased density of SV clusters along axons, and the size of the RPSV, suggesting that O-GlcNAcylation of synapsin I at Thr-87 may be a mechanism to modulate presynaptic plasticity. 24280219 5 69 theme RPSV 600:603 arg1 depression 625:634 increased synaptic depression 606:634 increased synaptic depression 606:634 Disruption of synapsin I function results in reduced size of the RPSV, increased synaptic depression, memory deficits, and epilepsy. 24280219 5 69 theme RPSV 600:603 arg1 deficits 644:651 memory deficits 637:651 memory deficits 637:651 Disruption of synapsin I function results in reduced size of the RPSV, increased synaptic depression, memory deficits, and epilepsy. 24280219 5 69 theme RPSV 600:603 arg1 epilepsy 658:665 epilepsy 658:665 epilepsy 658:665 Disruption of synapsin I function results in reduced size of the RPSV, increased synaptic depression, memory deficits, and epilepsy. 24280219 5 69 theme RPSV 600:603 arg1 size 588:591 reduced size 580:591 reduced size of the RPSV 580:603 Disruption of synapsin I function results in reduced size of the RPSV, increased synaptic depression, memory deficits, and epilepsy. 24280219 9 70 theme regulatory 1052:1061 arg1 regions 1063:1069 the regulatory regions 1048:1069 the regulatory regions on synapsin I. Expression of synapsin I where a single O-GlcNAc site Thr-87 was mutated to alanine in primary hippocampal neurons 1048:1199 All O-GlcNAc sites mapped within the regulatory regions on synapsin I. Expression of synapsin I where a single O-GlcNAc site Thr-87 was mutated to alanine in primary hippocampal neurons dramatically increased localization of synapsin I to synapses, increased density of SV clusters along axons, and the size of the RPSV, suggesting that O-GlcNAcylation of synapsin I at Thr-87 may be a mechanism to modulate presynaptic plasticity. 24280219 0 71 theme β-N-acetylglucosamine 9:29 arg1 thr-87 47:52 O-linked β-N-acetylglucosamine (O-GlcNAc) site thr-87 0:52 O-linked β-N-acetylglucosamine (O-GlcNAc) site thr-87 0:52 O-linked β-N-acetylglucosamine (O-GlcNAc) site thr-87 regulates synapsin I localization to synapses and size of the reserve pool of synaptic vesicles. 24280219 3 72 theme synaptic 406:413 arg1 RPSV 425:428 RPSV 425:428 RPSV 425:428 An important mechanism in presynaptic plasticity is the establishment of the reserve pool of synaptic vesicles (RPSV). 24280219 3 72 theme synaptic 406:413 arg1 vesicles 415:422 synaptic vesicles 406:422 synaptic vesicles (RPSV) 406:429 An important mechanism in presynaptic plasticity is the establishment of the reserve pool of synaptic vesicles (RPSV). 24280219 0 73 theme O-GlcNAc 32:39 arg1 thr-87 47:52 O-linked β-N-acetylglucosamine (O-GlcNAc) site thr-87 0:52 O-linked β-N-acetylglucosamine (O-GlcNAc) site thr-87 0:52 O-linked β-N-acetylglucosamine (O-GlcNAc) site thr-87 regulates synapsin I localization to synapses and size of the reserve pool of synaptic vesicles. 24280219 5 74 theme reduced 580:586 arg1 size 588:591 reduced size 580:591 reduced size of the RPSV 580:603 Disruption of synapsin I function results in reduced size of the RPSV, increased synaptic depression, memory deficits, and epilepsy. 24280219 3 75 theme pool 398:401 arg1 establishment 369:381 the establishment 365:381 the establishment of the reserve pool of synaptic vesicles (RPSV) 365:429 An important mechanism in presynaptic plasticity is the establishment of the reserve pool of synaptic vesicles (RPSV). 24280219 3 75 theme pool 398:401 arg1 mechanism 326:334 An important mechanism 313:334 An important mechanism in presynaptic plasticity 313:360 An important mechanism in presynaptic plasticity is the establishment of the reserve pool of synaptic vesicles (RPSV). 24280219 9 76 theme I. 1083:1084 arg1 Expression 1086:1095 synapsin I. Expression 1074:1095 synapsin I. Expression of synapsin I where a single O-GlcNAc site Thr-87 was mutated to alanine in primary hippocampal neurons 1074:1199 All O-GlcNAc sites mapped within the regulatory regions on synapsin I. Expression of synapsin I where a single O-GlcNAc site Thr-87 was mutated to alanine in primary hippocampal neurons dramatically increased localization of synapsin I to synapses, increased density of SV clusters along axons, and the size of the RPSV, suggesting that O-GlcNAcylation of synapsin I at Thr-87 may be a mechanism to modulate presynaptic plasticity. 24280219 4 77 with association 440:450 arg1 SVs 490:492 SVs 490:492 SVs 490:492 Dynamic association of synapsin I with synaptic vesicles (SVs) regulates the size and release of RPSV. 24280219 4 77 with association 440:450 arg1 vesicles 480:487 synaptic vesicles 471:487 synaptic vesicles (SVs) 471:493 Dynamic association of synapsin I with synaptic vesicles (SVs) regulates the size and release of RPSV. 24280219 0 78 theme site 42:45 arg1 thr-87 47:52 O-linked β-N-acetylglucosamine (O-GlcNAc) site thr-87 0:52 O-linked β-N-acetylglucosamine (O-GlcNAc) site thr-87 0:52 O-linked β-N-acetylglucosamine (O-GlcNAc) site thr-87 regulates synapsin I localization to synapses and size of the reserve pool of synaptic vesicles. 24280219 8 79 theme O-GlcNAc 893:900 arg1 sites 902:906 three novel O-GlcNAc sites 881:906 three novel O-GlcNAc sites 881:906 We identified three novel O-GlcNAc sites on synapsin I, two of which are known Ca(2+)/calmodulin-dependent protein kinase II phosphorylation sites. 24280219 6 80 theme presynaptic 748:758 arg1 plasticity 760:769 presynaptic plasticity 748:769 presynaptic plasticity 748:769 Here, we investigate whether O-GlcNAc directly regulates synapsin I function in presynaptic plasticity. 24280219 4 81 dep size 509:512 arg1 the 505:507 the 505:507 the 505:507 Dynamic association of synapsin I with synaptic vesicles (SVs) regulates the size and release of RPSV. 24280219 6 82 from function 736:743 arg1 plasticity 760:769 presynaptic plasticity 748:769 presynaptic plasticity 748:769 Here, we investigate whether O-GlcNAc directly regulates synapsin I function in presynaptic plasticity. 24280219 11 83 theme synapsin 1786:1793 arg1 association 1771:1781 the association 1767:1781 the association of synapsin I with SVs 1767:1804 We discuss the possibility that O-GlcNAcylation of Thr-87 interferes with folding of the ALPS motif, providing a means for regulating the association of synapsin I with SVs as a mechanism contributing to synapsin I localization and RPSV generation. 24280219 9 84 theme RPSV 1330:1333 arg1 synapses 1254:1261 synapses 1254:1261 synapses 1254:1261 All O-GlcNAc sites mapped within the regulatory regions on synapsin I. Expression of synapsin I where a single O-GlcNAc site Thr-87 was mutated to alanine in primary hippocampal neurons dramatically increased localization of synapsin I to synapses, increased density of SV clusters along axons, and the size of the RPSV, suggesting that O-GlcNAcylation of synapsin I at Thr-87 may be a mechanism to modulate presynaptic plasticity. 24280219 9 84 theme RPSV 1330:1333 arg1 density 1274:1280 increased density 1264:1280 increased density of SV clusters along axons 1264:1307 All O-GlcNAc sites mapped within the regulatory regions on synapsin I. Expression of synapsin I where a single O-GlcNAc site Thr-87 was mutated to alanine in primary hippocampal neurons dramatically increased localization of synapsin I to synapses, increased density of SV clusters along axons, and the size of the RPSV, suggesting that O-GlcNAcylation of synapsin I at Thr-87 may be a mechanism to modulate presynaptic plasticity. 24280219 9 84 theme RPSV 1330:1333 arg1 size 1318:1321 the size 1314:1321 the size of the RPSV 1314:1333 All O-GlcNAc sites mapped within the regulatory regions on synapsin I. Expression of synapsin I where a single O-GlcNAc site Thr-87 was mutated to alanine in primary hippocampal neurons dramatically increased localization of synapsin I to synapses, increased density of SV clusters along axons, and the size of the RPSV, suggesting that O-GlcNAcylation of synapsin I at Thr-87 may be a mechanism to modulate presynaptic plasticity. 24280219 9 85 from regions 1063:1069 arg1 Expression 1086:1095 synapsin I. Expression 1074:1095 synapsin I. Expression of synapsin I where a single O-GlcNAc site Thr-87 was mutated to alanine in primary hippocampal neurons 1074:1199 All O-GlcNAc sites mapped within the regulatory regions on synapsin I. Expression of synapsin I where a single O-GlcNAc site Thr-87 was mutated to alanine in primary hippocampal neurons dramatically increased localization of synapsin I to synapses, increased density of SV clusters along axons, and the size of the RPSV, suggesting that O-GlcNAcylation of synapsin I at Thr-87 may be a mechanism to modulate presynaptic plasticity. 24280219 6 86 theme synapsin 725:732 arg1 function 736:743 synapsin I function 725:743 synapsin I function in presynaptic plasticity 725:769 Here, we investigate whether O-GlcNAc directly regulates synapsin I function in presynaptic plasticity. 24280219 9 87 theme O-GlcNAc 1126:1133 arg1 site 1135:1138 a single O-GlcNAc site Thr-87 1117:1145 a single O-GlcNAc site Thr-87 1117:1145 All O-GlcNAc sites mapped within the regulatory regions on synapsin I. Expression of synapsin I where a single O-GlcNAc site Thr-87 was mutated to alanine in primary hippocampal neurons dramatically increased localization of synapsin I to synapses, increased density of SV clusters along axons, and the size of the RPSV, suggesting that O-GlcNAcylation of synapsin I at Thr-87 may be a mechanism to modulate presynaptic plasticity. 24280219 3 88 from mechanism 326:334 arg1 plasticity 351:360 presynaptic plasticity 339:360 presynaptic plasticity 339:360 An important mechanism in presynaptic plasticity is the establishment of the reserve pool of synaptic vesicles (RPSV). 26683050 10 0 from CSF 1548:1550 arg1 alterations 1495:1505 alterations 1495:1505 alterations of afucosylation and bisecting GlcNAc in CSF from MS cases 1495:1564 Third, hypothesis-free regression analysis revealed that alterations of afucosylation and bisecting GlcNAc in CSF from MS cases peaked 2-3 months after the last relapse. 26683050 6 1 theme glycosylation 977:989 arg1 patterns 991:998 IgG1 glycosylation patterns 972:998 IgG1 glycosylation patterns 972:998 First, IgG1 glycosylation patterns were different in CSF vs. serum, in the MS group and even in control donors without intrathecal IgG synthesis. 26683050 2 2 theme sclerosis 326:334 arg1 production 264:273 Intrathecal production 252:273 Intrathecal production of IgG 252:280 Intrathecal production of IgG, especially IgG1, is a hallmark of multiple sclerosis (MS), but nothing is known about IgG Fc glycosylation in MS and in cerebrospinal fluid (CSF) in general. 26683050 2 2 theme sclerosis 326:334 arg1 hallmark 305:312 a hallmark 303:312 a hallmark of multiple sclerosis (MS) 303:339 Intrathecal production of IgG, especially IgG1, is a hallmark of multiple sclerosis (MS), but nothing is known about IgG Fc glycosylation in MS and in cerebrospinal fluid (CSF) in general. 26683050 2 3 theme IgG 278:280 arg1 IgG1 294:297 IgG1 294:297 especially IgG1 283:297 Intrathecal production of IgG, especially IgG1, is a hallmark of multiple sclerosis (MS), but nothing is known about IgG Fc glycosylation in MS and in cerebrospinal fluid (CSF) in general. 26683050 2 3 theme IgG 278:280 arg1 production 264:273 Intrathecal production 252:273 Intrathecal production of IgG 252:280 Intrathecal production of IgG, especially IgG1, is a hallmark of multiple sclerosis (MS), but nothing is known about IgG Fc glycosylation in MS and in cerebrospinal fluid (CSF) in general. 26683050 2 3 theme IgG 278:280 arg1 hallmark 305:312 a hallmark 303:312 a hallmark of multiple sclerosis (MS) 303:339 Intrathecal production of IgG, especially IgG1, is a hallmark of multiple sclerosis (MS), but nothing is known about IgG Fc glycosylation in MS and in cerebrospinal fluid (CSF) in general. 26683050 3 4 theme paired 634:639 arg1 CSF 641:643 48 paired CSF and serum samples 631:661 CSF 641:643 METHODS: We applied mass spectrometry of tryptic Fc glycopeptides to analyze IgG Fc glycosylation (sialylation, galactosylation, fucosylation, and bisecting N-acetylglucosamine (GlcNAc)) in 48 paired CSF and serum samples from adult patients with MS or a first demyelinating event highly suggestive of MS (designated as MS cases), and from healthy volunteers and patients with other non-inflammatory diseases (control group). 26683050 3 5 theme mass 461:464 arg1 spectrometry 466:477 mass spectrometry 461:477 mass spectrometry of tryptic Fc glycopeptides 461:505 METHODS: We applied mass spectrometry of tryptic Fc glycopeptides to analyze IgG Fc glycosylation (sialylation, galactosylation, fucosylation, and bisecting N-acetylglucosamine (GlcNAc)) in 48 paired CSF and serum samples from adult patients with MS or a first demyelinating event highly suggestive of MS (designated as MS cases), and from healthy volunteers and patients with other non-inflammatory diseases (control group). 26683050 10 6 theme hypothesis-free 1445:1459 arg1 analysis 1472:1479 hypothesis-free regression analysis 1445:1479 hypothesis-free regression analysis 1445:1479 Third, hypothesis-free regression analysis revealed that alterations of afucosylation and bisecting GlcNAc in CSF from MS cases peaked 2-3 months after the last relapse. 26683050 3 7 theme adult 668:672 arg1 patients 674:681 adult patients 668:681 adult patients with MS or a first demyelinating event highly suggestive of MS (designated as MS cases) 668:769 METHODS: We applied mass spectrometry of tryptic Fc glycopeptides to analyze IgG Fc glycosylation (sialylation, galactosylation, fucosylation, and bisecting N-acetylglucosamine (GlcNAc)) in 48 paired CSF and serum samples from adult patients with MS or a first demyelinating event highly suggestive of MS (designated as MS cases), and from healthy volunteers and patients with other non-inflammatory diseases (control group). 26683050 3 8 dep glycosylation 525:537 arg1 sialylation 540:550 sialylation 540:550 sialylation 540:550 METHODS: We applied mass spectrometry of tryptic Fc glycopeptides to analyze IgG Fc glycosylation (sialylation, galactosylation, fucosylation, and bisecting N-acetylglucosamine (GlcNAc)) in 48 paired CSF and serum samples from adult patients with MS or a first demyelinating event highly suggestive of MS (designated as MS cases), and from healthy volunteers and patients with other non-inflammatory diseases (control group). 26683050 3 9 gly glycosylation 525:537 arg1 CSF 641:643 48 paired CSF and serum samples 631:661 CSF 641:643 METHODS: We applied mass spectrometry of tryptic Fc glycopeptides to analyze IgG Fc glycosylation (sialylation, galactosylation, fucosylation, and bisecting N-acetylglucosamine (GlcNAc)) in 48 paired CSF and serum samples from adult patients with MS or a first demyelinating event highly suggestive of MS (designated as MS cases), and from healthy volunteers and patients with other non-inflammatory diseases (control group). 26683050 9 10 theme effector 1418:1425 arg1 functions 1427:1435 IgG effector functions 1414:1435 IgG effector functions 1414:1435 Elevated bisecting GlcNAc and reduced galactosylation are known to enhance IgG effector functions. 26683050 3 11 theme Fc 490:491 arg1 glycopeptides 493:505 tryptic Fc glycopeptides 482:505 tryptic Fc glycopeptides 482:505 METHODS: We applied mass spectrometry of tryptic Fc glycopeptides to analyze IgG Fc glycosylation (sialylation, galactosylation, fucosylation, and bisecting N-acetylglucosamine (GlcNAc)) in 48 paired CSF and serum samples from adult patients with MS or a first demyelinating event highly suggestive of MS (designated as MS cases), and from healthy volunteers and patients with other non-inflammatory diseases (control group). 26683050 3 12 dep sialylation 540:550 arg1 N-acetylglucosamine 598:616 bisecting N-acetylglucosamine 588:616 bisecting N-acetylglucosamine (GlcNAc) 588:625 METHODS: We applied mass spectrometry of tryptic Fc glycopeptides to analyze IgG Fc glycosylation (sialylation, galactosylation, fucosylation, and bisecting N-acetylglucosamine (GlcNAc)) in 48 paired CSF and serum samples from adult patients with MS or a first demyelinating event highly suggestive of MS (designated as MS cases), and from healthy volunteers and patients with other non-inflammatory diseases (control group). 26683050 3 12 dep sialylation 540:550 arg1 GlcNAc 619:624 GlcNAc 619:624 GlcNAc 619:624 METHODS: We applied mass spectrometry of tryptic Fc glycopeptides to analyze IgG Fc glycosylation (sialylation, galactosylation, fucosylation, and bisecting N-acetylglucosamine (GlcNAc)) in 48 paired CSF and serum samples from adult patients with MS or a first demyelinating event highly suggestive of MS (designated as MS cases), and from healthy volunteers and patients with other non-inflammatory diseases (control group). 26683050 3 12 dep sialylation 540:550 arg1 fucosylation 570:581 fucosylation 570:581 fucosylation 570:581 METHODS: We applied mass spectrometry of tryptic Fc glycopeptides to analyze IgG Fc glycosylation (sialylation, galactosylation, fucosylation, and bisecting N-acetylglucosamine (GlcNAc)) in 48 paired CSF and serum samples from adult patients with MS or a first demyelinating event highly suggestive of MS (designated as MS cases), and from healthy volunteers and patients with other non-inflammatory diseases (control group). 26683050 3 12 dep sialylation 540:550 arg1 galactosylation 553:567 galactosylation 553:567 galactosylation 553:567 METHODS: We applied mass spectrometry of tryptic Fc glycopeptides to analyze IgG Fc glycosylation (sialylation, galactosylation, fucosylation, and bisecting N-acetylglucosamine (GlcNAc)) in 48 paired CSF and serum samples from adult patients with MS or a first demyelinating event highly suggestive of MS (designated as MS cases), and from healthy volunteers and patients with other non-inflammatory diseases (control group). 26683050 12 13 theme IgG1 1796:1799 arg1 glycosylation 1804:1816 IgG1 Fc glycosylation 1796:1816 IgG1 Fc glycosylation 1796:1816 CONCLUSIONS: The CNS compartment as well as the inflammatory milieu in MS affect IgG1 Fc glycosylation. 26683050 1 14 theme conserved 205:213 arg1 site 231:234 a conserved N-glycosylation site 203:234 a conserved N-glycosylation site in the Fc part 203:249 BACKGROUND: Immunoglobulin G (IgG) effector functions are regulated by the composition of glycans attached to a conserved N-glycosylation site in the Fc part. 26683050 6 15 theme IgG 1096:1098 arg1 synthesis 1100:1108 intrathecal IgG synthesis 1084:1108 intrathecal IgG synthesis 1084:1108 First, IgG1 glycosylation patterns were different in CSF vs. serum, in the MS group and even in control donors without intrathecal IgG synthesis. 26683050 11 16 theme IgG 1681:1683 arg1 synthesis 1685:1693 intrathecal IgG synthesis 1669:1693 intrathecal IgG synthesis 1669:1693 Fourth, CSF IgG1 glycosylation correlated with the degree of intrathecal IgG synthesis and CSF cell count. 26683050 3 17 theme IgG 518:520 arg1 glycosylation 525:537 IgG Fc glycosylation 518:537 IgG Fc glycosylation (sialylation, galactosylation, fucosylation, and bisecting N-acetylglucosamine (GlcNAc)) in 48 paired CSF and serum samples from adult patients with MS or a first demyelinating event highly suggestive of MS (designated as MS cases), and from healthy volunteers and patients with other non-inflammatory diseases (control group) 518:864 METHODS: We applied mass spectrometry of tryptic Fc glycopeptides to analyze IgG Fc glycosylation (sialylation, galactosylation, fucosylation, and bisecting N-acetylglucosamine (GlcNAc)) in 48 paired CSF and serum samples from adult patients with MS or a first demyelinating event highly suggestive of MS (designated as MS cases), and from healthy volunteers and patients with other non-inflammatory diseases (control group). 26683050 3 18 theme MS 761:762 arg1 cases 764:768 MS cases 761:768 MS cases 761:768 METHODS: We applied mass spectrometry of tryptic Fc glycopeptides to analyze IgG Fc glycosylation (sialylation, galactosylation, fucosylation, and bisecting N-acetylglucosamine (GlcNAc)) in 48 paired CSF and serum samples from adult patients with MS or a first demyelinating event highly suggestive of MS (designated as MS cases), and from healthy volunteers and patients with other non-inflammatory diseases (control group). 26683050 1 19 from site 231:234 arg1 part 246:249 the Fc part 239:249 the Fc part 239:249 BACKGROUND: Immunoglobulin G (IgG) effector functions are regulated by the composition of glycans attached to a conserved N-glycosylation site in the Fc part. 26683050 3 20 dep MS 743:744 arg1 designated 747:756 designated 747:756 designated as MS cases 747:768 METHODS: We applied mass spectrometry of tryptic Fc glycopeptides to analyze IgG Fc glycosylation (sialylation, galactosylation, fucosylation, and bisecting N-acetylglucosamine (GlcNAc)) in 48 paired CSF and serum samples from adult patients with MS or a first demyelinating event highly suggestive of MS (designated as MS cases), and from healthy volunteers and patients with other non-inflammatory diseases (control group). 26683050 9 21 theme bisecting 1348:1356 arg1 GlcNAc 1358:1363 Elevated bisecting GlcNAc 1339:1363 Elevated bisecting GlcNAc 1339:1363 Elevated bisecting GlcNAc and reduced galactosylation are known to enhance IgG effector functions. 26683050 4 22 theme p 867:867 arg1 values 869:874 p values 867:874 p values 867:874 p values were adjusted for multiple testing. 26683050 6 23 theme control 1061:1067 arg1 donors 1069:1074 control donors 1061:1074 control donors 1061:1074 First, IgG1 glycosylation patterns were different in CSF vs. serum, in the MS group and even in control donors without intrathecal IgG synthesis. 26683050 3 24 theme first 696:700 arg1 event 716:720 a first demyelinating event 694:720 a first demyelinating event highly suggestive of MS (designated as MS cases) 694:769 METHODS: We applied mass spectrometry of tryptic Fc glycopeptides to analyze IgG Fc glycosylation (sialylation, galactosylation, fucosylation, and bisecting N-acetylglucosamine (GlcNAc)) in 48 paired CSF and serum samples from adult patients with MS or a first demyelinating event highly suggestive of MS (designated as MS cases), and from healthy volunteers and patients with other non-inflammatory diseases (control group). 26683050 2 25 from glycosylation 376:388 arg1 MS 393:394 MS 393:394 MS 393:394 Intrathecal production of IgG, especially IgG1, is a hallmark of multiple sclerosis (MS), but nothing is known about IgG Fc glycosylation in MS and in cerebrospinal fluid (CSF) in general. 26683050 2 25 from glycosylation 376:388 arg1 CSF 424:426 CSF 424:426 CSF 424:426 Intrathecal production of IgG, especially IgG1, is a hallmark of multiple sclerosis (MS), but nothing is known about IgG Fc glycosylation in MS and in cerebrospinal fluid (CSF) in general. 26683050 2 25 from glycosylation 376:388 arg1 fluid 417:421 cerebrospinal fluid 403:421 cerebrospinal fluid (CSF) in general 403:438 Intrathecal production of IgG, especially IgG1, is a hallmark of multiple sclerosis (MS), but nothing is known about IgG Fc glycosylation in MS and in cerebrospinal fluid (CSF) in general. 26683050 3 26 theme MS 743:744 arg1 suggestive 729:738 suggestive 729:738 suggestive 729:738 METHODS: We applied mass spectrometry of tryptic Fc glycopeptides to analyze IgG Fc glycosylation (sialylation, galactosylation, fucosylation, and bisecting N-acetylglucosamine (GlcNAc)) in 48 paired CSF and serum samples from adult patients with MS or a first demyelinating event highly suggestive of MS (designated as MS cases), and from healthy volunteers and patients with other non-inflammatory diseases (control group). 26683050 12 27 theme inflammatory 1763:1774 arg1 milieu 1776:1781 the inflammatory milieu 1759:1781 The CNS compartment as well as the inflammatory milieu in MS 1728:1787 CONCLUSIONS: The CNS compartment as well as the inflammatory milieu in MS affect IgG1 Fc glycosylation. 26683050 6 28 from donors 1069:1074 arg1 different 1005:1013 different 1005:1013 different 1005:1013 First, IgG1 glycosylation patterns were different in CSF vs. serum, in the MS group and even in control donors without intrathecal IgG synthesis. 26683050 3 29 theme suggestive 729:738 arg1 event 716:720 a first demyelinating event 694:720 a first demyelinating event highly suggestive of MS (designated as MS cases) 694:769 METHODS: We applied mass spectrometry of tryptic Fc glycopeptides to analyze IgG Fc glycosylation (sialylation, galactosylation, fucosylation, and bisecting N-acetylglucosamine (GlcNAc)) in 48 paired CSF and serum samples from adult patients with MS or a first demyelinating event highly suggestive of MS (designated as MS cases), and from healthy volunteers and patients with other non-inflammatory diseases (control group). 26683050 13 30 theme Fc 1879:1880 arg1 functions 1891:1899 Fc effector functions 1879:1899 Fc effector functions 1879:1899 In MS, the CSF IgG1 glycosylation has features that enhance Fc effector functions. 26683050 1 31 theme effector 128:135 arg1 functions 137:145 Immunoglobulin G (IgG) effector functions 105:145 Immunoglobulin G (IgG) effector functions 105:145 BACKGROUND: Immunoglobulin G (IgG) effector functions are regulated by the composition of glycans attached to a conserved N-glycosylation site in the Fc part. 26683050 10 32 theme bisecting 1528:1536 arg1 GlcNAc 1538:1543 bisecting GlcNAc 1528:1543 bisecting GlcNAc 1528:1543 Third, hypothesis-free regression analysis revealed that alterations of afucosylation and bisecting GlcNAc in CSF from MS cases peaked 2-3 months after the last relapse. 26683050 3 33 theme healthy 781:787 arg1 volunteers 789:798 healthy volunteers 781:798 healthy volunteers 781:798 METHODS: We applied mass spectrometry of tryptic Fc glycopeptides to analyze IgG Fc glycosylation (sialylation, galactosylation, fucosylation, and bisecting N-acetylglucosamine (GlcNAc)) in 48 paired CSF and serum samples from adult patients with MS or a first demyelinating event highly suggestive of MS (designated as MS cases), and from healthy volunteers and patients with other non-inflammatory diseases (control group). 26683050 2 34 from fluid 417:421 arg1 general 432:438 general 432:438 general 432:438 Intrathecal production of IgG, especially IgG1, is a hallmark of multiple sclerosis (MS), but nothing is known about IgG Fc glycosylation in MS and in cerebrospinal fluid (CSF) in general. 26683050 10 35 theme afucosylation 1510:1522 arg1 alterations 1495:1505 alterations 1495:1505 alterations of afucosylation and bisecting GlcNAc in CSF from MS cases 1495:1564 Third, hypothesis-free regression analysis revealed that alterations of afucosylation and bisecting GlcNAc in CSF from MS cases peaked 2-3 months after the last relapse. 26683050 0 36 theme Pro-inflammatory 0:15 arg1 pattern 17:23 Pro-inflammatory pattern 0:23 Pro-inflammatory pattern of IgG1 Fc glycosylation in multiple sclerosis 0:70 Pro-inflammatory pattern of IgG1 Fc glycosylation in multiple sclerosis cerebrospinal fluid. 26683050 10 37 gly afucosylation 1510:1522 arg1 CSF 1548:1550 CSF 1548:1550 CSF 1548:1550 Third, hypothesis-free regression analysis revealed that alterations of afucosylation and bisecting GlcNAc in CSF from MS cases peaked 2-3 months after the last relapse. 26683050 0 38 dep fluid 86:90 arg1 pattern 17:23 Pro-inflammatory pattern 0:23 Pro-inflammatory pattern of IgG1 Fc glycosylation in multiple sclerosis 0:70 Pro-inflammatory pattern of IgG1 Fc glycosylation in multiple sclerosis cerebrospinal fluid. 26683050 3 39 theme non-inflammatory 824:839 arg1 diseases 841:848 other non-inflammatory diseases 818:848 other non-inflammatory diseases 818:848 METHODS: We applied mass spectrometry of tryptic Fc glycopeptides to analyze IgG Fc glycosylation (sialylation, galactosylation, fucosylation, and bisecting N-acetylglucosamine (GlcNAc)) in 48 paired CSF and serum samples from adult patients with MS or a first demyelinating event highly suggestive of MS (designated as MS cases), and from healthy volunteers and patients with other non-inflammatory diseases (control group). 26683050 2 40 theme Fc 373:374 arg1 glycosylation 376:388 IgG Fc glycosylation 369:388 IgG Fc glycosylation in MS and in cerebrospinal fluid (CSF) in general 369:438 Intrathecal production of IgG, especially IgG1, is a hallmark of multiple sclerosis (MS), but nothing is known about IgG Fc glycosylation in MS and in cerebrospinal fluid (CSF) in general. 26683050 1 41 theme G 120:120 arg1 functions 137:145 Immunoglobulin G (IgG) effector functions 105:145 Immunoglobulin G (IgG) effector functions 105:145 BACKGROUND: Immunoglobulin G (IgG) effector functions are regulated by the composition of glycans attached to a conserved N-glycosylation site in the Fc part. 26683050 3 42 from glycosylation 525:537 arg1 CSF 641:643 48 paired CSF and serum samples 631:661 CSF 641:643 METHODS: We applied mass spectrometry of tryptic Fc glycopeptides to analyze IgG Fc glycosylation (sialylation, galactosylation, fucosylation, and bisecting N-acetylglucosamine (GlcNAc)) in 48 paired CSF and serum samples from adult patients with MS or a first demyelinating event highly suggestive of MS (designated as MS cases), and from healthy volunteers and patients with other non-inflammatory diseases (control group). 26683050 3 42 from glycosylation 525:537 arg1 patients 674:681 adult patients 668:681 adult patients with MS or a first demyelinating event highly suggestive of MS (designated as MS cases) 668:769 METHODS: We applied mass spectrometry of tryptic Fc glycopeptides to analyze IgG Fc glycosylation (sialylation, galactosylation, fucosylation, and bisecting N-acetylglucosamine (GlcNAc)) in 48 paired CSF and serum samples from adult patients with MS or a first demyelinating event highly suggestive of MS (designated as MS cases), and from healthy volunteers and patients with other non-inflammatory diseases (control group). 26683050 0 43 theme Fc 33:34 arg1 glycosylation 36:48 IgG1 Fc glycosylation 28:48 IgG1 Fc glycosylation 28:48 Pro-inflammatory pattern of IgG1 Fc glycosylation in multiple sclerosis cerebrospinal fluid. 26683050 12 44 theme CNS 1732:1734 arg1 compartment 1736:1746 The CNS compartment 1728:1746 The CNS compartment as well as the inflammatory milieu in MS 1728:1787 CONCLUSIONS: The CNS compartment as well as the inflammatory milieu in MS affect IgG1 Fc glycosylation. 26683050 10 45 from afucosylation 1510:1522 arg1 CSF 1548:1550 CSF 1548:1550 CSF 1548:1550 Third, hypothesis-free regression analysis revealed that alterations of afucosylation and bisecting GlcNAc in CSF from MS cases peaked 2-3 months after the last relapse. 26683050 7 46 theme glycosylation 1153:1165 arg1 patterns 1167:1174 IgG1 glycosylation patterns 1148:1174 IgG1 glycosylation patterns 1148:1174 Second, in MS patients vs. controls, IgG1 glycosylation patterns were altered in CSF, but not in serum. 26683050 2 47 theme cerebrospinal 403:415 arg1 CSF 424:426 CSF 424:426 CSF 424:426 Intrathecal production of IgG, especially IgG1, is a hallmark of multiple sclerosis (MS), but nothing is known about IgG Fc glycosylation in MS and in cerebrospinal fluid (CSF) in general. 26683050 2 47 theme cerebrospinal 403:415 arg1 fluid 417:421 cerebrospinal fluid 403:421 cerebrospinal fluid (CSF) in general 403:438 Intrathecal production of IgG, especially IgG1, is a hallmark of multiple sclerosis (MS), but nothing is known about IgG Fc glycosylation in MS and in cerebrospinal fluid (CSF) in general. 26683050 8 48 theme MS 1245:1246 arg1 group 1248:1252 the MS group 1241:1252 the MS group 1241:1252 Specifically, in CSF from the MS group, bisecting GlcNAc were elevated, and afucosylation and galactosylation were reduced. 26683050 6 49 from different 1005:1013 arg1 donors 1069:1074 control donors 1061:1074 control donors 1061:1074 First, IgG1 glycosylation patterns were different in CSF vs. serum, in the MS group and even in control donors without intrathecal IgG synthesis. 26683050 6 49 from different 1005:1013 arg1 group 1043:1047 the MS group 1036:1047 the MS group 1036:1047 First, IgG1 glycosylation patterns were different in CSF vs. serum, in the MS group and even in control donors without intrathecal IgG synthesis. 26683050 6 49 from different 1005:1013 arg1 CSF 1018:1020 CSF 1018:1020 CSF 1018:1020 First, IgG1 glycosylation patterns were different in CSF vs. serum, in the MS group and even in control donors without intrathecal IgG synthesis. 26683050 2 50 theme multiple 317:324 arg1 MS 337:338 MS 337:338 MS 337:338 Intrathecal production of IgG, especially IgG1, is a hallmark of multiple sclerosis (MS), but nothing is known about IgG Fc glycosylation in MS and in cerebrospinal fluid (CSF) in general. 26683050 2 50 theme multiple 317:324 arg1 sclerosis 326:334 multiple sclerosis 317:334 multiple sclerosis (MS) 317:339 Intrathecal production of IgG, especially IgG1, is a hallmark of multiple sclerosis (MS), but nothing is known about IgG Fc glycosylation in MS and in cerebrospinal fluid (CSF) in general. 26683050 1 51 attach attached 191:198 arg2 glycans 183:189 glycans 183:189 glycans attached to a conserved N-glycosylation site in the Fc part 183:249 BACKGROUND: Immunoglobulin G (IgG) effector functions are regulated by the composition of glycans attached to a conserved N-glycosylation site in the Fc part. 26683050 1 51 attach attached 191:198 arg1 site 231:234 a conserved N-glycosylation site 203:234 a conserved N-glycosylation site in the Fc part 203:249 BACKGROUND: Immunoglobulin G (IgG) effector functions are regulated by the composition of glycans attached to a conserved N-glycosylation site in the Fc part. 26683050 6 52 from CSF 1018:1020 arg1 different 1005:1013 different 1005:1013 different 1005:1013 First, IgG1 glycosylation patterns were different in CSF vs. serum, in the MS group and even in control donors without intrathecal IgG synthesis. 26683050 11 53 theme cell 1703:1706 arg1 count 1708:1712 CSF cell count 1699:1712 CSF cell count 1699:1712 Fourth, CSF IgG1 glycosylation correlated with the degree of intrathecal IgG synthesis and CSF cell count. 26683050 1 54 theme N-glycosylation 215:229 arg1 site 231:234 a conserved N-glycosylation site 203:234 a conserved N-glycosylation site in the Fc part 203:249 BACKGROUND: Immunoglobulin G (IgG) effector functions are regulated by the composition of glycans attached to a conserved N-glycosylation site in the Fc part. 26683050 13 55 theme CSF 1830:1832 arg1 glycosylation 1839:1851 the CSF IgG1 glycosylation 1826:1851 the CSF IgG1 glycosylation 1826:1851 In MS, the CSF IgG1 glycosylation has features that enhance Fc effector functions. 26683050 7 56 theme MS 1122:1123 arg1 patients 1125:1132 MS patients 1122:1132 MS patients 1122:1132 Second, in MS patients vs. controls, IgG1 glycosylation patterns were altered in CSF, but not in serum. 26683050 13 57 contain has 1853:1855 arg2 features 1857:1864 features 1857:1864 features that enhance Fc effector functions 1857:1899 In MS, the CSF IgG1 glycosylation has features that enhance Fc effector functions. 26683050 13 57 contain has 1853:1855 arg1 glycosylation 1839:1851 the CSF IgG1 glycosylation 1826:1851 the CSF IgG1 glycosylation 1826:1851 In MS, the CSF IgG1 glycosylation has features that enhance Fc effector functions. 26683050 1 58 theme Fc 243:244 arg1 part 246:249 the Fc part 239:249 the Fc part 239:249 BACKGROUND: Immunoglobulin G (IgG) effector functions are regulated by the composition of glycans attached to a conserved N-glycosylation site in the Fc part. 26683050 10 59 from cases 1560:1564 arg1 afucosylation 1510:1522 afucosylation 1510:1522 afucosylation 1510:1522 Third, hypothesis-free regression analysis revealed that alterations of afucosylation and bisecting GlcNAc in CSF from MS cases peaked 2-3 months after the last relapse. 26683050 10 59 from cases 1560:1564 arg1 GlcNAc 1538:1543 bisecting GlcNAc 1528:1543 bisecting GlcNAc 1528:1543 Third, hypothesis-free regression analysis revealed that alterations of afucosylation and bisecting GlcNAc in CSF from MS cases peaked 2-3 months after the last relapse. 26683050 10 59 from cases 1560:1564 arg1 alterations 1495:1505 alterations 1495:1505 alterations of afucosylation and bisecting GlcNAc in CSF from MS cases 1495:1564 Third, hypothesis-free regression analysis revealed that alterations of afucosylation and bisecting GlcNAc in CSF from MS cases peaked 2-3 months after the last relapse. 26683050 6 60 theme IgG1 972:975 arg1 patterns 991:998 IgG1 glycosylation patterns 972:998 IgG1 glycosylation patterns 972:998 First, IgG1 glycosylation patterns were different in CSF vs. serum, in the MS group and even in control donors without intrathecal IgG synthesis. 26683050 11 61 theme count 1708:1712 arg1 degree 1659:1664 the degree 1655:1664 the degree of intrathecal IgG synthesis and CSF cell count 1655:1712 Fourth, CSF IgG1 glycosylation correlated with the degree of intrathecal IgG synthesis and CSF cell count. 26683050 3 62 theme serum 649:653 arg1 samples 655:661 48 paired CSF and serum samples 631:661 samples 655:661 METHODS: We applied mass spectrometry of tryptic Fc glycopeptides to analyze IgG Fc glycosylation (sialylation, galactosylation, fucosylation, and bisecting N-acetylglucosamine (GlcNAc)) in 48 paired CSF and serum samples from adult patients with MS or a first demyelinating event highly suggestive of MS (designated as MS cases), and from healthy volunteers and patients with other non-inflammatory diseases (control group). 26683050 10 63 from alterations 1495:1505 arg1 CSF 1548:1550 CSF 1548:1550 CSF 1548:1550 Third, hypothesis-free regression analysis revealed that alterations of afucosylation and bisecting GlcNAc in CSF from MS cases peaked 2-3 months after the last relapse. 26683050 10 63 from alterations 1495:1505 arg1 cases 1560:1564 MS cases 1557:1564 MS cases 1557:1564 Third, hypothesis-free regression analysis revealed that alterations of afucosylation and bisecting GlcNAc in CSF from MS cases peaked 2-3 months after the last relapse. 26683050 6 64 theme MS 1040:1041 arg1 group 1043:1047 the MS group 1036:1047 the MS group 1036:1047 First, IgG1 glycosylation patterns were different in CSF vs. serum, in the MS group and even in control donors without intrathecal IgG synthesis. 26683050 10 65 theme regression 1461:1470 arg1 analysis 1472:1479 hypothesis-free regression analysis 1445:1479 hypothesis-free regression analysis 1445:1479 Third, hypothesis-free regression analysis revealed that alterations of afucosylation and bisecting GlcNAc in CSF from MS cases peaked 2-3 months after the last relapse. 26683050 3 66 theme glycopeptides 493:505 arg1 spectrometry 466:477 mass spectrometry 461:477 mass spectrometry of tryptic Fc glycopeptides 461:505 METHODS: We applied mass spectrometry of tryptic Fc glycopeptides to analyze IgG Fc glycosylation (sialylation, galactosylation, fucosylation, and bisecting N-acetylglucosamine (GlcNAc)) in 48 paired CSF and serum samples from adult patients with MS or a first demyelinating event highly suggestive of MS (designated as MS cases), and from healthy volunteers and patients with other non-inflammatory diseases (control group). 26683050 12 67 from compartment 1736:1746 arg1 MS 1786:1787 MS 1786:1787 MS 1786:1787 CONCLUSIONS: The CNS compartment as well as the inflammatory milieu in MS affect IgG1 Fc glycosylation. 26683050 11 68 theme intrathecal 1669:1679 arg1 synthesis 1685:1693 intrathecal IgG synthesis 1669:1693 intrathecal IgG synthesis 1669:1693 Fourth, CSF IgG1 glycosylation correlated with the degree of intrathecal IgG synthesis and CSF cell count. 26683050 3 69 theme tryptic 482:488 arg1 glycopeptides 493:505 tryptic Fc glycopeptides 482:505 tryptic Fc glycopeptides 482:505 METHODS: We applied mass spectrometry of tryptic Fc glycopeptides to analyze IgG Fc glycosylation (sialylation, galactosylation, fucosylation, and bisecting N-acetylglucosamine (GlcNAc)) in 48 paired CSF and serum samples from adult patients with MS or a first demyelinating event highly suggestive of MS (designated as MS cases), and from healthy volunteers and patients with other non-inflammatory diseases (control group). 26683050 3 70 theme Fc 522:523 arg1 glycosylation 525:537 IgG Fc glycosylation 518:537 IgG Fc glycosylation (sialylation, galactosylation, fucosylation, and bisecting N-acetylglucosamine (GlcNAc)) in 48 paired CSF and serum samples from adult patients with MS or a first demyelinating event highly suggestive of MS (designated as MS cases), and from healthy volunteers and patients with other non-inflammatory diseases (control group) 518:864 METHODS: We applied mass spectrometry of tryptic Fc glycopeptides to analyze IgG Fc glycosylation (sialylation, galactosylation, fucosylation, and bisecting N-acetylglucosamine (GlcNAc)) in 48 paired CSF and serum samples from adult patients with MS or a first demyelinating event highly suggestive of MS (designated as MS cases), and from healthy volunteers and patients with other non-inflammatory diseases (control group). 26683050 1 71 theme glycans 183:189 arg1 composition 168:178 the composition 164:178 the composition of glycans attached to a conserved N-glycosylation site in the Fc part 164:249 BACKGROUND: Immunoglobulin G (IgG) effector functions are regulated by the composition of glycans attached to a conserved N-glycosylation site in the Fc part. 26683050 11 72 theme CSF 1699:1701 arg1 count 1708:1712 CSF cell count 1699:1712 CSF cell count 1699:1712 Fourth, CSF IgG1 glycosylation correlated with the degree of intrathecal IgG synthesis and CSF cell count. 26683050 12 73 theme Fc 1801:1802 arg1 glycosylation 1804:1816 IgG1 Fc glycosylation 1796:1816 IgG1 Fc glycosylation 1796:1816 CONCLUSIONS: The CNS compartment as well as the inflammatory milieu in MS affect IgG1 Fc glycosylation. 26683050 6 74 theme intrathecal 1084:1094 arg1 synthesis 1100:1108 intrathecal IgG synthesis 1084:1108 intrathecal IgG synthesis 1084:1108 First, IgG1 glycosylation patterns were different in CSF vs. serum, in the MS group and even in control donors without intrathecal IgG synthesis. 26683050 3 75 gly glycopeptides 493:505 arg2 glycopeptides 493:505 tryptic Fc glycopeptides 482:505 tryptic Fc glycopeptides 482:505 METHODS: We applied mass spectrometry of tryptic Fc glycopeptides to analyze IgG Fc glycosylation (sialylation, galactosylation, fucosylation, and bisecting N-acetylglucosamine (GlcNAc)) in 48 paired CSF and serum samples from adult patients with MS or a first demyelinating event highly suggestive of MS (designated as MS cases), and from healthy volunteers and patients with other non-inflammatory diseases (control group). 26683050 11 76 theme synthesis 1685:1693 arg1 degree 1659:1664 the degree 1655:1664 the degree of intrathecal IgG synthesis and CSF cell count 1655:1712 Fourth, CSF IgG1 glycosylation correlated with the degree of intrathecal IgG synthesis and CSF cell count. 26683050 3 77 with volunteers 789:798 arg1 diseases 841:848 other non-inflammatory diseases 818:848 other non-inflammatory diseases 818:848 METHODS: We applied mass spectrometry of tryptic Fc glycopeptides to analyze IgG Fc glycosylation (sialylation, galactosylation, fucosylation, and bisecting N-acetylglucosamine (GlcNAc)) in 48 paired CSF and serum samples from adult patients with MS or a first demyelinating event highly suggestive of MS (designated as MS cases), and from healthy volunteers and patients with other non-inflammatory diseases (control group). 26683050 2 78 theme Intrathecal 252:262 arg1 IgG1 294:297 IgG1 294:297 especially IgG1 283:297 Intrathecal production of IgG, especially IgG1, is a hallmark of multiple sclerosis (MS), but nothing is known about IgG Fc glycosylation in MS and in cerebrospinal fluid (CSF) in general. 26683050 2 78 theme Intrathecal 252:262 arg1 production 264:273 Intrathecal production 252:273 Intrathecal production of IgG 252:280 Intrathecal production of IgG, especially IgG1, is a hallmark of multiple sclerosis (MS), but nothing is known about IgG Fc glycosylation in MS and in cerebrospinal fluid (CSF) in general. 26683050 2 78 theme Intrathecal 252:262 arg1 hallmark 305:312 a hallmark 303:312 a hallmark of multiple sclerosis (MS) 303:339 Intrathecal production of IgG, especially IgG1, is a hallmark of multiple sclerosis (MS), but nothing is known about IgG Fc glycosylation in MS and in cerebrospinal fluid (CSF) in general. 26683050 9 79 theme Elevated 1339:1346 arg1 GlcNAc 1358:1363 Elevated bisecting GlcNAc 1339:1363 Elevated bisecting GlcNAc 1339:1363 Elevated bisecting GlcNAc and reduced galactosylation are known to enhance IgG effector functions. 26683050 3 80 from volunteers 789:798 arg1 glycosylation 525:537 IgG Fc glycosylation 518:537 IgG Fc glycosylation (sialylation, galactosylation, fucosylation, and bisecting N-acetylglucosamine (GlcNAc)) in 48 paired CSF and serum samples from adult patients with MS or a first demyelinating event highly suggestive of MS (designated as MS cases), and from healthy volunteers and patients with other non-inflammatory diseases (control group) 518:864 METHODS: We applied mass spectrometry of tryptic Fc glycopeptides to analyze IgG Fc glycosylation (sialylation, galactosylation, fucosylation, and bisecting N-acetylglucosamine (GlcNAc)) in 48 paired CSF and serum samples from adult patients with MS or a first demyelinating event highly suggestive of MS (designated as MS cases), and from healthy volunteers and patients with other non-inflammatory diseases (control group). 26683050 11 81 theme CSF 1616:1618 arg1 glycosylation 1625:1637 CSF IgG1 glycosylation 1616:1637 CSF IgG1 glycosylation 1616:1637 Fourth, CSF IgG1 glycosylation correlated with the degree of intrathecal IgG synthesis and CSF cell count. 26683050 0 82 theme cerebrospinal 72:84 arg1 fluid 86:90 cerebrospinal fluid 72:90 cerebrospinal fluid 72:90 Pro-inflammatory pattern of IgG1 Fc glycosylation in multiple sclerosis cerebrospinal fluid. 26683050 5 83 theme main 951:954 arg1 results 956:962 four main results 946:962 four main results 946:962 RESULTS: Our experiments revealed four main results. 26683050 12 84 from milieu 1776:1781 arg1 MS 1786:1787 MS 1786:1787 MS 1786:1787 CONCLUSIONS: The CNS compartment as well as the inflammatory milieu in MS affect IgG1 Fc glycosylation. 26683050 11 85 theme IgG1 1620:1623 arg1 glycosylation 1625:1637 CSF IgG1 glycosylation 1616:1637 CSF IgG1 glycosylation 1616:1637 Fourth, CSF IgG1 glycosylation correlated with the degree of intrathecal IgG synthesis and CSF cell count. 26683050 3 86 from patients 804:811 arg1 glycosylation 525:537 IgG Fc glycosylation 518:537 IgG Fc glycosylation (sialylation, galactosylation, fucosylation, and bisecting N-acetylglucosamine (GlcNAc)) in 48 paired CSF and serum samples from adult patients with MS or a first demyelinating event highly suggestive of MS (designated as MS cases), and from healthy volunteers and patients with other non-inflammatory diseases (control group) 518:864 METHODS: We applied mass spectrometry of tryptic Fc glycopeptides to analyze IgG Fc glycosylation (sialylation, galactosylation, fucosylation, and bisecting N-acetylglucosamine (GlcNAc)) in 48 paired CSF and serum samples from adult patients with MS or a first demyelinating event highly suggestive of MS (designated as MS cases), and from healthy volunteers and patients with other non-inflammatory diseases (control group). 26683050 3 87 theme demyelinating 702:714 arg1 event 716:720 a first demyelinating event 694:720 a first demyelinating event highly suggestive of MS (designated as MS cases) 694:769 METHODS: We applied mass spectrometry of tryptic Fc glycopeptides to analyze IgG Fc glycosylation (sialylation, galactosylation, fucosylation, and bisecting N-acetylglucosamine (GlcNAc)) in 48 paired CSF and serum samples from adult patients with MS or a first demyelinating event highly suggestive of MS (designated as MS cases), and from healthy volunteers and patients with other non-inflammatory diseases (control group). 26683050 9 88 theme reduced 1369:1375 arg1 galactosylation 1377:1391 reduced galactosylation 1369:1391 reduced galactosylation 1369:1391 Elevated bisecting GlcNAc and reduced galactosylation are known to enhance IgG effector functions. 26683050 0 89 from pattern 17:23 arg1 sclerosis 62:70 multiple sclerosis 53:70 multiple sclerosis 53:70 Pro-inflammatory pattern of IgG1 Fc glycosylation in multiple sclerosis cerebrospinal fluid. 26683050 1 90 gly N-glycosylation 215:229 arg2 site 231:234 a conserved N-glycosylation site 203:234 a conserved N-glycosylation site in the Fc part 203:249 BACKGROUND: Immunoglobulin G (IgG) effector functions are regulated by the composition of glycans attached to a conserved N-glycosylation site in the Fc part. 26683050 6 91 from group 1043:1047 arg1 different 1005:1013 different 1005:1013 different 1005:1013 First, IgG1 glycosylation patterns were different in CSF vs. serum, in the MS group and even in control donors without intrathecal IgG synthesis. 26683050 3 92 with patients 804:811 arg1 diseases 841:848 other non-inflammatory diseases 818:848 other non-inflammatory diseases 818:848 METHODS: We applied mass spectrometry of tryptic Fc glycopeptides to analyze IgG Fc glycosylation (sialylation, galactosylation, fucosylation, and bisecting N-acetylglucosamine (GlcNAc)) in 48 paired CSF and serum samples from adult patients with MS or a first demyelinating event highly suggestive of MS (designated as MS cases), and from healthy volunteers and patients with other non-inflammatory diseases (control group). 26683050 13 93 theme effector 1882:1889 arg1 functions 1891:1899 Fc effector functions 1879:1899 Fc effector functions 1879:1899 In MS, the CSF IgG1 glycosylation has features that enhance Fc effector functions. 26683050 9 94 theme IgG 1414:1416 arg1 functions 1427:1435 IgG effector functions 1414:1435 IgG effector functions 1414:1435 Elevated bisecting GlcNAc and reduced galactosylation are known to enhance IgG effector functions. 26683050 3 95 from patients 674:681 arg1 CSF 641:643 48 paired CSF and serum samples 631:661 CSF 641:643 METHODS: We applied mass spectrometry of tryptic Fc glycopeptides to analyze IgG Fc glycosylation (sialylation, galactosylation, fucosylation, and bisecting N-acetylglucosamine (GlcNAc)) in 48 paired CSF and serum samples from adult patients with MS or a first demyelinating event highly suggestive of MS (designated as MS cases), and from healthy volunteers and patients with other non-inflammatory diseases (control group). 26683050 3 95 from patients 674:681 arg1 glycosylation 525:537 IgG Fc glycosylation 518:537 IgG Fc glycosylation (sialylation, galactosylation, fucosylation, and bisecting N-acetylglucosamine (GlcNAc)) in 48 paired CSF and serum samples from adult patients with MS or a first demyelinating event highly suggestive of MS (designated as MS cases), and from healthy volunteers and patients with other non-inflammatory diseases (control group) 518:864 METHODS: We applied mass spectrometry of tryptic Fc glycopeptides to analyze IgG Fc glycosylation (sialylation, galactosylation, fucosylation, and bisecting N-acetylglucosamine (GlcNAc)) in 48 paired CSF and serum samples from adult patients with MS or a first demyelinating event highly suggestive of MS (designated as MS cases), and from healthy volunteers and patients with other non-inflammatory diseases (control group). 26683050 0 96 theme IgG1 28:31 arg1 glycosylation 36:48 IgG1 Fc glycosylation 28:48 IgG1 Fc glycosylation 28:48 Pro-inflammatory pattern of IgG1 Fc glycosylation in multiple sclerosis cerebrospinal fluid. 26683050 3 97 with patients 674:681 arg1 event 716:720 a first demyelinating event 694:720 a first demyelinating event highly suggestive of MS (designated as MS cases) 694:769 METHODS: We applied mass spectrometry of tryptic Fc glycopeptides to analyze IgG Fc glycosylation (sialylation, galactosylation, fucosylation, and bisecting N-acetylglucosamine (GlcNAc)) in 48 paired CSF and serum samples from adult patients with MS or a first demyelinating event highly suggestive of MS (designated as MS cases), and from healthy volunteers and patients with other non-inflammatory diseases (control group). 26683050 3 97 with patients 674:681 arg1 MS 688:689 MS 688:689 MS 688:689 METHODS: We applied mass spectrometry of tryptic Fc glycopeptides to analyze IgG Fc glycosylation (sialylation, galactosylation, fucosylation, and bisecting N-acetylglucosamine (GlcNAc)) in 48 paired CSF and serum samples from adult patients with MS or a first demyelinating event highly suggestive of MS (designated as MS cases), and from healthy volunteers and patients with other non-inflammatory diseases (control group). 26683050 1 98 theme Immunoglobulin 105:118 arg1 IgG 123:125 IgG 123:125 IgG 123:125 BACKGROUND: Immunoglobulin G (IgG) effector functions are regulated by the composition of glycans attached to a conserved N-glycosylation site in the Fc part. 26683050 1 98 theme Immunoglobulin 105:118 arg1 G 120:120 Immunoglobulin G 105:120 Immunoglobulin G (IgG) effector functions 105:145 BACKGROUND: Immunoglobulin G (IgG) effector functions are regulated by the composition of glycans attached to a conserved N-glycosylation site in the Fc part. 26683050 8 99 from group 1248:1252 arg1 CSF 1232:1234 CSF 1232:1234 CSF from the MS group 1232:1252 Specifically, in CSF from the MS group, bisecting GlcNAc were elevated, and afucosylation and galactosylation were reduced. 26683050 2 100 theme IgG 369:371 arg1 glycosylation 376:388 IgG Fc glycosylation 369:388 IgG Fc glycosylation in MS and in cerebrospinal fluid (CSF) in general 369:438 Intrathecal production of IgG, especially IgG1, is a hallmark of multiple sclerosis (MS), but nothing is known about IgG Fc glycosylation in MS and in cerebrospinal fluid (CSF) in general. 26683050 0 101 theme glycosylation 36:48 arg1 pattern 17:23 Pro-inflammatory pattern 0:23 Pro-inflammatory pattern of IgG1 Fc glycosylation in multiple sclerosis 0:70 Pro-inflammatory pattern of IgG1 Fc glycosylation in multiple sclerosis cerebrospinal fluid. 26683050 3 102 theme other 818:822 arg1 diseases 841:848 other non-inflammatory diseases 818:848 other non-inflammatory diseases 818:848 METHODS: We applied mass spectrometry of tryptic Fc glycopeptides to analyze IgG Fc glycosylation (sialylation, galactosylation, fucosylation, and bisecting N-acetylglucosamine (GlcNAc)) in 48 paired CSF and serum samples from adult patients with MS or a first demyelinating event highly suggestive of MS (designated as MS cases), and from healthy volunteers and patients with other non-inflammatory diseases (control group). 26683050 7 103 theme IgG1 1148:1151 arg1 patterns 1167:1174 IgG1 glycosylation patterns 1148:1174 IgG1 glycosylation patterns 1148:1174 Second, in MS patients vs. controls, IgG1 glycosylation patterns were altered in CSF, but not in serum. 26683050 10 104 theme GlcNAc 1538:1543 arg1 alterations 1495:1505 alterations 1495:1505 alterations of afucosylation and bisecting GlcNAc in CSF from MS cases 1495:1564 Third, hypothesis-free regression analysis revealed that alterations of afucosylation and bisecting GlcNAc in CSF from MS cases peaked 2-3 months after the last relapse. 26683050 0 105 theme multiple 53:60 arg1 sclerosis 62:70 multiple sclerosis 53:70 multiple sclerosis 53:70 Pro-inflammatory pattern of IgG1 Fc glycosylation in multiple sclerosis cerebrospinal fluid. 26683050 4 106 theme multiple 894:901 arg1 testing 903:909 multiple testing 894:909 multiple testing 894:909 p values were adjusted for multiple testing. 26683050 3 107 theme control 851:857 arg1 group 859:863 control group 851:863 control group 851:863 METHODS: We applied mass spectrometry of tryptic Fc glycopeptides to analyze IgG Fc glycosylation (sialylation, galactosylation, fucosylation, and bisecting N-acetylglucosamine (GlcNAc)) in 48 paired CSF and serum samples from adult patients with MS or a first demyelinating event highly suggestive of MS (designated as MS cases), and from healthy volunteers and patients with other non-inflammatory diseases (control group). 26683050 3 107 theme control 851:857 arg1 patients 804:811 patients 804:811 patients with other non-inflammatory diseases (control group) 804:864 METHODS: We applied mass spectrometry of tryptic Fc glycopeptides to analyze IgG Fc glycosylation (sialylation, galactosylation, fucosylation, and bisecting N-acetylglucosamine (GlcNAc)) in 48 paired CSF and serum samples from adult patients with MS or a first demyelinating event highly suggestive of MS (designated as MS cases), and from healthy volunteers and patients with other non-inflammatory diseases (control group). 26683050 3 108 theme bisecting 588:596 arg1 N-acetylglucosamine 598:616 bisecting N-acetylglucosamine 588:616 bisecting N-acetylglucosamine (GlcNAc) 588:625 METHODS: We applied mass spectrometry of tryptic Fc glycopeptides to analyze IgG Fc glycosylation (sialylation, galactosylation, fucosylation, and bisecting N-acetylglucosamine (GlcNAc)) in 48 paired CSF and serum samples from adult patients with MS or a first demyelinating event highly suggestive of MS (designated as MS cases), and from healthy volunteers and patients with other non-inflammatory diseases (control group). 26683050 3 108 theme bisecting 588:596 arg1 GlcNAc 619:624 GlcNAc 619:624 GlcNAc 619:624 METHODS: We applied mass spectrometry of tryptic Fc glycopeptides to analyze IgG Fc glycosylation (sialylation, galactosylation, fucosylation, and bisecting N-acetylglucosamine (GlcNAc)) in 48 paired CSF and serum samples from adult patients with MS or a first demyelinating event highly suggestive of MS (designated as MS cases), and from healthy volunteers and patients with other non-inflammatory diseases (control group). 26683050 10 109 theme MS 1557:1558 arg1 cases 1560:1564 MS cases 1557:1564 MS cases 1557:1564 Third, hypothesis-free regression analysis revealed that alterations of afucosylation and bisecting GlcNAc in CSF from MS cases peaked 2-3 months after the last relapse. 26683050 2 110 gly glycosylation 376:388 arg1 MS 393:394 MS 393:394 MS 393:394 Intrathecal production of IgG, especially IgG1, is a hallmark of multiple sclerosis (MS), but nothing is known about IgG Fc glycosylation in MS and in cerebrospinal fluid (CSF) in general. 26683050 2 110 gly glycosylation 376:388 arg1 CSF 424:426 CSF 424:426 CSF 424:426 Intrathecal production of IgG, especially IgG1, is a hallmark of multiple sclerosis (MS), but nothing is known about IgG Fc glycosylation in MS and in cerebrospinal fluid (CSF) in general. 26683050 2 110 gly glycosylation 376:388 arg1 fluid 417:421 cerebrospinal fluid 403:421 cerebrospinal fluid (CSF) in general 403:438 Intrathecal production of IgG, especially IgG1, is a hallmark of multiple sclerosis (MS), but nothing is known about IgG Fc glycosylation in MS and in cerebrospinal fluid (CSF) in general. 26683050 10 111 from GlcNAc 1538:1543 arg1 CSF 1548:1550 CSF 1548:1550 CSF 1548:1550 Third, hypothesis-free regression analysis revealed that alterations of afucosylation and bisecting GlcNAc in CSF from MS cases peaked 2-3 months after the last relapse. 26683050 8 112 theme bisecting 1255:1263 arg1 GlcNAc 1265:1270 bisecting GlcNAc 1255:1270 bisecting GlcNAc 1255:1270 Specifically, in CSF from the MS group, bisecting GlcNAc were elevated, and afucosylation and galactosylation were reduced. 26683050 13 113 theme IgG1 1834:1837 arg1 glycosylation 1839:1851 the CSF IgG1 glycosylation 1826:1851 the CSF IgG1 glycosylation 1826:1851 In MS, the CSF IgG1 glycosylation has features that enhance Fc effector functions. 26683050 10 114 theme last 1594:1597 arg1 relapse 1599:1605 the last relapse 1590:1605 the last relapse 1590:1605 Third, hypothesis-free regression analysis revealed that alterations of afucosylation and bisecting GlcNAc in CSF from MS cases peaked 2-3 months after the last relapse. 24685145 5 0 theme peptide-binding 782:796 arg1 groove 798:803 a defined peptide-binding groove 772:803 a defined peptide-binding groove adjacent to the active site that can accommodate peptides in opposite orientations 772:886 X-ray structures of complexes between N33/Tusc3 and two different peptides as model substrates reveal a defined peptide-binding groove adjacent to the active site that can accommodate peptides in opposite orientations. 24685145 7 1 theme human 1166:1170 arg1 glycoproteins 1172:1184 human glycoproteins 1166:1184 human glycoproteins 1166:1184 Our results support a model in which N33/Tusc3 increases glycosylation efficiency for a subset of human glycoproteins by slowing glycoprotein folding. 24685145 1 2 theme proteins 174:181 arg1 glycosylation 157:169 N-linked glycosylation 148:169 N-linked glycosylation of proteins in the endoplasmic reticulum (ER) 148:215 N-linked glycosylation of proteins in the endoplasmic reticulum (ER) is essential in eukaryotes and catalyzed by oligosaccharyl transferase (OST). 24685145 4 3 theme ER 590:591 arg1 lumen 593:597 the ER lumen 586:597 the ER lumen that may form transient mixed disulfide complexes with OST substrates 586:667 Here, we show that N33/Tusc3 possesses a membrane-anchored N-terminal thioredoxin domain located in the ER lumen that may form transient mixed disulfide complexes with OST substrates. 24685145 0 4 theme N33/Tusc3 86:94 arg1 specificity 30:40 substrate specificity 20:40 substrate specificity of human oligosaccharyl transferase subunit N33/Tusc3 20:94 Structural basis of substrate specificity of human oligosaccharyl transferase subunit N33/Tusc3 and its role in regulating protein N-glycosylation. 24685145 3 5 from defects 404:410 arg1 N33/Tusc3 427:435 the subunit N33/Tusc3 415:435 the subunit N33/Tusc3 415:435 The subunit N33/Tusc3 is a tumor suppressor candidate, and defects in the subunit N33/Tusc3 are linked with nonsyndromic mental retardation. 24685145 7 6 theme glycoproteins 1172:1184 arg1 subset 1156:1161 a subset 1154:1161 a subset of human glycoproteins 1154:1184 Our results support a model in which N33/Tusc3 increases glycosylation efficiency for a subset of human glycoproteins by slowing glycoprotein folding. 24685145 6 7 theme Structural 889:898 arg1 data 916:919 Structural and biochemical data 889:919 Structural and biochemical data 889:919 Structural and biochemical data show that N33/Tusc3 prefers peptides bearing a hydrophobic residue two residues away from the cysteine forming the mixed disulfide with N33/Tusc3. 24685145 1 8 theme oligosaccharyl 261:274 arg1 OST 289:291 OST 289:291 OST 289:291 N-linked glycosylation of proteins in the endoplasmic reticulum (ER) is essential in eukaryotes and catalyzed by oligosaccharyl transferase (OST). 24685145 1 8 theme oligosaccharyl 261:274 arg1 transferase 276:286 oligosaccharyl transferase 261:286 oligosaccharyl transferase (OST) 261:292 N-linked glycosylation of proteins in the endoplasmic reticulum (ER) is essential in eukaryotes and catalyzed by oligosaccharyl transferase (OST). 24685145 5 9 theme X-ray 670:674 arg1 structures 676:685 X-ray structures 670:685 X-ray structures of complexes between N33/Tusc3 and two different peptides as model substrates 670:763 X-ray structures of complexes between N33/Tusc3 and two different peptides as model substrates reveal a defined peptide-binding groove adjacent to the active site that can accommodate peptides in opposite orientations. 24685145 2 10 theme Human 295:299 arg1 OST 301:303 Human OST 295:303 Human OST 295:303 Human OST is a hetero-oligomer of seven subunits. 24685145 2 10 theme Human 295:299 arg1 hetero-oligomer 310:324 a hetero-oligomer 308:324 a hetero-oligomer of seven subunits 308:342 Human OST is a hetero-oligomer of seven subunits. 24685145 4 11 from lumen 593:597 arg1 located 575:581 located 575:581 located 575:581 Here, we show that N33/Tusc3 possesses a membrane-anchored N-terminal thioredoxin domain located in the ER lumen that may form transient mixed disulfide complexes with OST substrates. 24685145 1 12 from glycosylation 157:169 arg1 reticulum 202:210 the endoplasmic reticulum 186:210 the endoplasmic reticulum (ER) 186:215 N-linked glycosylation of proteins in the endoplasmic reticulum (ER) is essential in eukaryotes and catalyzed by oligosaccharyl transferase (OST). 24685145 1 12 from glycosylation 157:169 arg1 ER 213:214 ER 213:214 ER 213:214 N-linked glycosylation of proteins in the endoplasmic reticulum (ER) is essential in eukaryotes and catalyzed by oligosaccharyl transferase (OST). 24685145 4 13 theme disulfide 629:637 arg1 complexes 639:647 transient mixed disulfide complexes 613:647 transient mixed disulfide complexes with OST substrates 613:667 Here, we show that N33/Tusc3 possesses a membrane-anchored N-terminal thioredoxin domain located in the ER lumen that may form transient mixed disulfide complexes with OST substrates. 24685145 4 14 contain possesses 515:523 arg2 domain 568:573 a membrane-anchored N-terminal thioredoxin domain 525:573 a membrane-anchored N-terminal thioredoxin domain located in the ER lumen that may form transient mixed disulfide complexes with OST substrates 525:667 Here, we show that N33/Tusc3 possesses a membrane-anchored N-terminal thioredoxin domain located in the ER lumen that may form transient mixed disulfide complexes with OST substrates. 24685145 4 14 contain possesses 515:523 arg1 N33/Tusc3 505:513 N33/Tusc3 505:513 N33/Tusc3 505:513 Here, we show that N33/Tusc3 possesses a membrane-anchored N-terminal thioredoxin domain located in the ER lumen that may form transient mixed disulfide complexes with OST substrates. 24685145 3 15 theme subunit 349:355 arg1 candidate 389:397 a tumor suppressor candidate 370:397 a tumor suppressor candidate 370:397 The subunit N33/Tusc3 is a tumor suppressor candidate, and defects in the subunit N33/Tusc3 are linked with nonsyndromic mental retardation. 24685145 3 15 theme subunit 349:355 arg1 N33/Tusc3 357:365 The subunit N33/Tusc3 345:365 The subunit N33/Tusc3 345:365 The subunit N33/Tusc3 is a tumor suppressor candidate, and defects in the subunit N33/Tusc3 are linked with nonsyndromic mental retardation. 24685145 7 16 theme glycoprotein 1197:1208 arg1 folding 1210:1216 glycoprotein folding 1197:1216 glycoprotein folding 1197:1216 Our results support a model in which N33/Tusc3 increases glycosylation efficiency for a subset of human glycoproteins by slowing glycoprotein folding. 24685145 4 17 from located 575:581 arg1 lumen 593:597 the ER lumen 586:597 the ER lumen that may form transient mixed disulfide complexes with OST substrates 586:667 Here, we show that N33/Tusc3 possesses a membrane-anchored N-terminal thioredoxin domain located in the ER lumen that may form transient mixed disulfide complexes with OST substrates. 24685145 1 18 theme endoplasmic 190:200 arg1 reticulum 202:210 the endoplasmic reticulum 186:210 the endoplasmic reticulum (ER) 186:215 N-linked glycosylation of proteins in the endoplasmic reticulum (ER) is essential in eukaryotes and catalyzed by oligosaccharyl transferase (OST). 24685145 1 18 theme endoplasmic 190:200 arg1 ER 213:214 ER 213:214 ER 213:214 N-linked glycosylation of proteins in the endoplasmic reticulum (ER) is essential in eukaryotes and catalyzed by oligosaccharyl transferase (OST). 24685145 3 19 theme suppressor 378:387 arg1 candidate 389:397 a tumor suppressor candidate 370:397 a tumor suppressor candidate 370:397 The subunit N33/Tusc3 is a tumor suppressor candidate, and defects in the subunit N33/Tusc3 are linked with nonsyndromic mental retardation. 24685145 3 19 theme suppressor 378:387 arg1 N33/Tusc3 357:365 The subunit N33/Tusc3 345:365 The subunit N33/Tusc3 345:365 The subunit N33/Tusc3 is a tumor suppressor candidate, and defects in the subunit N33/Tusc3 are linked with nonsyndromic mental retardation. 24685145 7 20 theme glycosylation 1125:1137 arg1 efficiency 1139:1148 glycosylation efficiency 1125:1148 glycosylation efficiency for a subset of human glycoproteins 1125:1184 Our results support a model in which N33/Tusc3 increases glycosylation efficiency for a subset of human glycoproteins by slowing glycoprotein folding. 24685145 1 21 gly glycosylation 157:169 arg1 reticulum 202:210 the endoplasmic reticulum 186:210 the endoplasmic reticulum (ER) 186:215 N-linked glycosylation of proteins in the endoplasmic reticulum (ER) is essential in eukaryotes and catalyzed by oligosaccharyl transferase (OST). 24685145 1 21 gly glycosylation 157:169 arg1 proteins 174:181 proteins 174:181 proteins 174:181 N-linked glycosylation of proteins in the endoplasmic reticulum (ER) is essential in eukaryotes and catalyzed by oligosaccharyl transferase (OST). 24685145 1 21 gly glycosylation 157:169 arg1 ER 213:214 ER 213:214 ER 213:214 N-linked glycosylation of proteins in the endoplasmic reticulum (ER) is essential in eukaryotes and catalyzed by oligosaccharyl transferase (OST). 24685145 0 22 theme Structural 0:9 arg1 basis 11:15 Structural basis 0:15 Structural basis of substrate specificity of human oligosaccharyl transferase subunit N33/Tusc3 0:94 Structural basis of substrate specificity of human oligosaccharyl transferase subunit N33/Tusc3 and its role in regulating protein N-glycosylation. 24685145 3 23 theme subunit 419:425 arg1 N33/Tusc3 427:435 the subunit N33/Tusc3 415:435 the subunit N33/Tusc3 415:435 The subunit N33/Tusc3 is a tumor suppressor candidate, and defects in the subunit N33/Tusc3 are linked with nonsyndromic mental retardation. 24685145 0 24 theme substrate 20:28 arg1 specificity 30:40 substrate specificity 20:40 substrate specificity of human oligosaccharyl transferase subunit N33/Tusc3 20:94 Structural basis of substrate specificity of human oligosaccharyl transferase subunit N33/Tusc3 and its role in regulating protein N-glycosylation. 24685145 4 25 theme thioredoxin 556:566 arg1 domain 568:573 a membrane-anchored N-terminal thioredoxin domain 525:573 a membrane-anchored N-terminal thioredoxin domain located in the ER lumen that may form transient mixed disulfide complexes with OST substrates 525:667 Here, we show that N33/Tusc3 possesses a membrane-anchored N-terminal thioredoxin domain located in the ER lumen that may form transient mixed disulfide complexes with OST substrates. 24685145 3 26 theme nonsyndromic 453:464 arg1 retardation 473:483 nonsyndromic mental retardation 453:483 nonsyndromic mental retardation 453:483 The subunit N33/Tusc3 is a tumor suppressor candidate, and defects in the subunit N33/Tusc3 are linked with nonsyndromic mental retardation. 24685145 3 27 theme tumor 372:376 arg1 candidate 389:397 a tumor suppressor candidate 370:397 a tumor suppressor candidate 370:397 The subunit N33/Tusc3 is a tumor suppressor candidate, and defects in the subunit N33/Tusc3 are linked with nonsyndromic mental retardation. 24685145 3 27 theme tumor 372:376 arg1 N33/Tusc3 357:365 The subunit N33/Tusc3 345:365 The subunit N33/Tusc3 345:365 The subunit N33/Tusc3 is a tumor suppressor candidate, and defects in the subunit N33/Tusc3 are linked with nonsyndromic mental retardation. 24685145 0 28 theme protein 123:129 arg1 N-glycosylation 131:145 protein N-glycosylation 123:145 protein N-glycosylation 123:145 Structural basis of substrate specificity of human oligosaccharyl transferase subunit N33/Tusc3 and its role in regulating protein N-glycosylation. 24685145 6 29 theme biochemical 904:914 arg1 data 916:919 Structural and biochemical data 889:919 Structural and biochemical data 889:919 Structural and biochemical data show that N33/Tusc3 prefers peptides bearing a hydrophobic residue two residues away from the cysteine forming the mixed disulfide with N33/Tusc3. 24685145 3 30 theme mental 466:471 arg1 retardation 473:483 nonsyndromic mental retardation 453:483 nonsyndromic mental retardation 453:483 The subunit N33/Tusc3 is a tumor suppressor candidate, and defects in the subunit N33/Tusc3 are linked with nonsyndromic mental retardation. 24685145 5 31 theme adjacent 805:812 arg1 groove 798:803 a defined peptide-binding groove 772:803 a defined peptide-binding groove adjacent to the active site that can accommodate peptides in opposite orientations 772:886 X-ray structures of complexes between N33/Tusc3 and two different peptides as model substrates reveal a defined peptide-binding groove adjacent to the active site that can accommodate peptides in opposite orientations. 24685145 4 32 theme located 575:581 arg1 domain 568:573 a membrane-anchored N-terminal thioredoxin domain 525:573 a membrane-anchored N-terminal thioredoxin domain located in the ER lumen that may form transient mixed disulfide complexes with OST substrates 525:667 Here, we show that N33/Tusc3 possesses a membrane-anchored N-terminal thioredoxin domain located in the ER lumen that may form transient mixed disulfide complexes with OST substrates. 24685145 5 33 theme different 726:734 arg1 peptides 736:743 two different peptides 722:743 two different peptides as model substrates 722:763 X-ray structures of complexes between N33/Tusc3 and two different peptides as model substrates reveal a defined peptide-binding groove adjacent to the active site that can accommodate peptides in opposite orientations. 24685145 5 34 theme opposite 866:873 arg1 orientations 875:886 opposite orientations 866:886 opposite orientations 866:886 X-ray structures of complexes between N33/Tusc3 and two different peptides as model substrates reveal a defined peptide-binding groove adjacent to the active site that can accommodate peptides in opposite orientations. 24685145 4 35 theme OST 654:656 arg1 substrates 658:667 OST substrates 654:667 OST substrates 654:667 Here, we show that N33/Tusc3 possesses a membrane-anchored N-terminal thioredoxin domain located in the ER lumen that may form transient mixed disulfide complexes with OST substrates. 24685145 0 36 theme specificity 30:40 arg1 role 104:107 its role 100:107 its role in regulating protein N-glycosylation 100:145 Structural basis of substrate specificity of human oligosaccharyl transferase subunit N33/Tusc3 and its role in regulating protein N-glycosylation. 24685145 0 36 theme specificity 30:40 arg1 basis 11:15 Structural basis 0:15 Structural basis of substrate specificity of human oligosaccharyl transferase subunit N33/Tusc3 0:94 Structural basis of substrate specificity of human oligosaccharyl transferase subunit N33/Tusc3 and its role in regulating protein N-glycosylation. 24685145 6 37 theme mixed 1036:1040 arg1 disulfide 1042:1050 the mixed disulfide 1032:1050 the mixed disulfide with N33/Tusc3 1032:1065 Structural and biochemical data show that N33/Tusc3 prefers peptides bearing a hydrophobic residue two residues away from the cysteine forming the mixed disulfide with N33/Tusc3. 24685145 5 38 theme model 748:752 arg1 substrates 754:763 model substrates 748:763 model substrates 748:763 X-ray structures of complexes between N33/Tusc3 and two different peptides as model substrates reveal a defined peptide-binding groove adjacent to the active site that can accommodate peptides in opposite orientations. 24685145 7 39 gly glycoprotein 1197:1208 arg1 glycoprotein 1197:1208 glycoprotein folding 1197:1216 glycoprotein folding 1197:1216 Our results support a model in which N33/Tusc3 increases glycosylation efficiency for a subset of human glycoproteins by slowing glycoprotein folding. 24685145 6 40 theme hydrophobic 968:978 arg1 residue 980:986 a hydrophobic residue 966:986 a hydrophobic residue two residues away from the cysteine forming the mixed disulfide with N33/Tusc3 966:1065 Structural and biochemical data show that N33/Tusc3 prefers peptides bearing a hydrophobic residue two residues away from the cysteine forming the mixed disulfide with N33/Tusc3. 24685145 0 41 theme oligosaccharyl 51:64 arg1 N33/Tusc3 86:94 human oligosaccharyl transferase subunit N33/Tusc3 45:94 human oligosaccharyl transferase subunit N33/Tusc3 45:94 Structural basis of substrate specificity of human oligosaccharyl transferase subunit N33/Tusc3 and its role in regulating protein N-glycosylation. 24685145 5 42 theme active 821:826 arg1 site 828:831 the active site 817:831 the active site that can accommodate peptides in opposite orientations 817:886 X-ray structures of complexes between N33/Tusc3 and two different peptides as model substrates reveal a defined peptide-binding groove adjacent to the active site that can accommodate peptides in opposite orientations. 24685145 5 43 theme defined 774:780 arg1 groove 798:803 a defined peptide-binding groove 772:803 a defined peptide-binding groove adjacent to the active site that can accommodate peptides in opposite orientations 772:886 X-ray structures of complexes between N33/Tusc3 and two different peptides as model substrates reveal a defined peptide-binding groove adjacent to the active site that can accommodate peptides in opposite orientations. 24685145 1 44 from essential 220:228 arg1 eukaryotes 233:242 eukaryotes 233:242 eukaryotes 233:242 N-linked glycosylation of proteins in the endoplasmic reticulum (ER) is essential in eukaryotes and catalyzed by oligosaccharyl transferase (OST). 24685145 0 45 theme human 45:49 arg1 N33/Tusc3 86:94 human oligosaccharyl transferase subunit N33/Tusc3 45:94 human oligosaccharyl transferase subunit N33/Tusc3 45:94 Structural basis of substrate specificity of human oligosaccharyl transferase subunit N33/Tusc3 and its role in regulating protein N-glycosylation. 24685145 4 46 theme N-terminal 545:554 arg1 domain 568:573 a membrane-anchored N-terminal thioredoxin domain 525:573 a membrane-anchored N-terminal thioredoxin domain located in the ER lumen that may form transient mixed disulfide complexes with OST substrates 525:667 Here, we show that N33/Tusc3 possesses a membrane-anchored N-terminal thioredoxin domain located in the ER lumen that may form transient mixed disulfide complexes with OST substrates. 24685145 1 47 link N-linked 148:155 arg1 glycosylation 157:169 N-linked glycosylation 148:169 N-linked glycosylation of proteins in the endoplasmic reticulum (ER) 148:215 N-linked glycosylation of proteins in the endoplasmic reticulum (ER) is essential in eukaryotes and catalyzed by oligosaccharyl transferase (OST). 24685145 5 48 from peptides 854:861 arg1 orientations 875:886 opposite orientations 866:886 opposite orientations 866:886 X-ray structures of complexes between N33/Tusc3 and two different peptides as model substrates reveal a defined peptide-binding groove adjacent to the active site that can accommodate peptides in opposite orientations. 24685145 2 49 theme subunits 335:342 arg1 OST 301:303 Human OST 295:303 Human OST 295:303 Human OST is a hetero-oligomer of seven subunits. 24685145 2 49 theme subunits 335:342 arg1 hetero-oligomer 310:324 a hetero-oligomer 308:324 a hetero-oligomer of seven subunits 308:342 Human OST is a hetero-oligomer of seven subunits. 24685145 4 50 theme membrane-anchored 527:543 arg1 domain 568:573 a membrane-anchored N-terminal thioredoxin domain 525:573 a membrane-anchored N-terminal thioredoxin domain located in the ER lumen that may form transient mixed disulfide complexes with OST substrates 525:667 Here, we show that N33/Tusc3 possesses a membrane-anchored N-terminal thioredoxin domain located in the ER lumen that may form transient mixed disulfide complexes with OST substrates. 24685145 1 51 from eukaryotes 233:242 arg1 essential 220:228 essential 220:228 essential 220:228 N-linked glycosylation of proteins in the endoplasmic reticulum (ER) is essential in eukaryotes and catalyzed by oligosaccharyl transferase (OST). 24685145 4 52 with complexes 639:647 arg1 substrates 658:667 OST substrates 654:667 OST substrates 654:667 Here, we show that N33/Tusc3 possesses a membrane-anchored N-terminal thioredoxin domain located in the ER lumen that may form transient mixed disulfide complexes with OST substrates. 24685145 1 53 theme N-linked 148:155 arg1 glycosylation 157:169 N-linked glycosylation 148:169 N-linked glycosylation of proteins in the endoplasmic reticulum (ER) 148:215 N-linked glycosylation of proteins in the endoplasmic reticulum (ER) is essential in eukaryotes and catalyzed by oligosaccharyl transferase (OST). 24685145 0 54 theme subunit 78:84 arg1 N33/Tusc3 86:94 human oligosaccharyl transferase subunit N33/Tusc3 45:94 human oligosaccharyl transferase subunit N33/Tusc3 45:94 Structural basis of substrate specificity of human oligosaccharyl transferase subunit N33/Tusc3 and its role in regulating protein N-glycosylation. 24685145 6 55 with disulfide 1042:1050 arg1 N33/Tusc3 1057:1065 N33/Tusc3 1057:1065 N33/Tusc3 1057:1065 Structural and biochemical data show that N33/Tusc3 prefers peptides bearing a hydrophobic residue two residues away from the cysteine forming the mixed disulfide with N33/Tusc3. 24685145 7 56 gly glycoproteins 1172:1184 arg1 glycoproteins 1172:1184 human glycoproteins 1166:1184 human glycoproteins 1166:1184 Our results support a model in which N33/Tusc3 increases glycosylation efficiency for a subset of human glycoproteins by slowing glycoprotein folding. 24685145 4 57 theme mixed 623:627 arg1 complexes 639:647 transient mixed disulfide complexes 613:647 transient mixed disulfide complexes with OST substrates 613:667 Here, we show that N33/Tusc3 possesses a membrane-anchored N-terminal thioredoxin domain located in the ER lumen that may form transient mixed disulfide complexes with OST substrates. 24685145 0 58 theme transferase 66:76 arg1 N33/Tusc3 86:94 human oligosaccharyl transferase subunit N33/Tusc3 45:94 human oligosaccharyl transferase subunit N33/Tusc3 45:94 Structural basis of substrate specificity of human oligosaccharyl transferase subunit N33/Tusc3 and its role in regulating protein N-glycosylation. 24685145 5 59 theme complexes 690:698 arg1 structures 676:685 X-ray structures 670:685 X-ray structures of complexes between N33/Tusc3 and two different peptides as model substrates 670:763 X-ray structures of complexes between N33/Tusc3 and two different peptides as model substrates reveal a defined peptide-binding groove adjacent to the active site that can accommodate peptides in opposite orientations. 24685145 4 60 theme transient 613:621 arg1 complexes 639:647 transient mixed disulfide complexes 613:647 transient mixed disulfide complexes with OST substrates 613:667 Here, we show that N33/Tusc3 possesses a membrane-anchored N-terminal thioredoxin domain located in the ER lumen that may form transient mixed disulfide complexes with OST substrates. 25484062 0 0 theme chromatography-mass 95:113 arg1 spectrometry 115:126 liquid chromatography-mass spectrometry 88:126 liquid chromatography-mass spectrometry 88:126 Versatile characterization of glycosylation modification in CTLA4-Ig fusion proteins by liquid chromatography-mass spectrometry. 25484062 5 1 theme versatile 823:831 arg1 spectrometry 797:808 Liquid chromatography-mass spectrometry 770:808 Liquid chromatography-mass spectrometry (LC-MS) 770:816 Liquid chromatography-mass spectrometry (LC-MS) is a versatile technique for characterizing N- and O-glycosylation modification of recombinant therapeutic proteins, including 3 levels: intact protein analysis, peptide mapping analysis, and released glycans analysis. 25484062 5 1 theme versatile 823:831 arg1 technique 833:841 a versatile technique 821:841 a versatile technique for characterizing N- and O-glycosylation modification of recombinant therapeutic proteins, including 3 levels: intact protein analysis, peptide mapping analysis, and released glycans analysis 821:1034 Liquid chromatography-mass spectrometry (LC-MS) is a versatile technique for characterizing N- and O-glycosylation modification of recombinant therapeutic proteins, including 3 levels: intact protein analysis, peptide mapping analysis, and released glycans analysis. 25484062 3 2 theme clinical 532:539 arg1 data 541:544 animal and clinical data 521:544 animal and clinical data needed to establish biosimilarity 521:578 For a CTLA4-Ig biosimilar development program, comparative analytical data, especially the glycosylation data, can influence decisions about the type and amount of animal and clinical data needed to establish biosimilarity. 25484062 4 3 dep clinical 604:611 arg1 experience 613:622 experience 613:622 experience 613:622 Because of the limited clinical experience with biosimilars before approval, a comprehensive level of knowledge about the biosimilar candidates is needed to achieve subsequent development. 25484062 0 4 theme liquid 88:93 arg1 spectrometry 115:126 liquid chromatography-mass spectrometry 88:126 liquid chromatography-mass spectrometry 88:126 Versatile characterization of glycosylation modification in CTLA4-Ig fusion proteins by liquid chromatography-mass spectrometry. 25484062 0 5 from characterization 10:25 arg1 proteins 76:83 CTLA4-Ig fusion proteins 60:83 CTLA4-Ig fusion proteins 60:83 Versatile characterization of glycosylation modification in CTLA4-Ig fusion proteins by liquid chromatography-mass spectrometry. 25484062 8 6 theme biosimilar 1555:1564 arg1 protein 1576:1582 a candidate biosimilar Fc-fusion protein 1543:1582 a candidate biosimilar Fc-fusion protein 1543:1582 This approach can be used to comprehensively research a candidate biosimilar Fc-fusion protein and provides a basis for future studies addressing the similarity of CTLA4-Ig biosimilars. 25484062 3 7 theme data 541:544 arg1 data 541:544 animal and clinical data 521:544 animal and clinical data needed to establish biosimilarity 521:578 For a CTLA4-Ig biosimilar development program, comparative analytical data, especially the glycosylation data, can influence decisions about the type and amount of animal and clinical data needed to establish biosimilarity. 25484062 3 7 theme data 541:544 arg1 amount 511:516 amount 511:516 amount 511:516 For a CTLA4-Ig biosimilar development program, comparative analytical data, especially the glycosylation data, can influence decisions about the type and amount of animal and clinical data needed to establish biosimilarity. 25484062 3 7 theme data 541:544 arg1 type 502:505 type 502:505 type 502:505 For a CTLA4-Ig biosimilar development program, comparative analytical data, especially the glycosylation data, can influence decisions about the type and amount of animal and clinical data needed to establish biosimilarity. 25484062 6 8 theme O-glycosylation 1286:1300 arg1 sites 1302:1306 the 4 occupied O-glycosylation sites 1271:1306 the 4 occupied O-glycosylation sites for the first time 1271:1325 In this report, an in-depth characterization of glycosylation of a candidate biosimilar was carried out using a systematic approach: N- and O-linked glycans were identified and electron-transfer dissociation was then used to pinpoint the 4 occupied O-glycosylation sites for the first time. 25484062 1 9 gly O-glycosylation 220:234 arg2 sites 236:240 multiple N- and O-glycosylation sites 204:240 multiple N- and O-glycosylation sites 204:240 CTLA4-Ig is a highly glycosylated therapeutic fusion protein that contains multiple N- and O-glycosylation sites. 25484062 4 10 with clinical 604:611 arg1 biosimilars 629:639 biosimilars 629:639 biosimilars before approval 629:655 Because of the limited clinical experience with biosimilars before approval, a comprehensive level of knowledge about the biosimilar candidates is needed to achieve subsequent development. 25484062 4 11 theme biosimilar 703:712 arg1 candidates 714:723 the biosimilar candidates 699:723 the biosimilar candidates 699:723 Because of the limited clinical experience with biosimilars before approval, a comprehensive level of knowledge about the biosimilar candidates is needed to achieve subsequent development. 25484062 6 12 theme in-depth 1056:1063 arg1 characterization 1065:1080 an in-depth characterization 1053:1080 an in-depth characterization of glycosylation of a candidate biosimilar 1053:1123 In this report, an in-depth characterization of glycosylation of a candidate biosimilar was carried out using a systematic approach: N- and O-linked glycans were identified and electron-transfer dissociation was then used to pinpoint the 4 occupied O-glycosylation sites for the first time. 25484062 7 13 theme glycan 1471:1476 arg1 profiling 1478:1486 released glycan profiling 1462:1486 released glycan profiling 1462:1486 As the results show, the approach provides a set of routine tools that combine accurate intact mass measurement, peptide mapping, and released glycan profiling. 25484062 1 14 contain contains 195:202 arg1 protein 182:188 a highly glycosylated therapeutic fusion protein 141:188 a highly glycosylated therapeutic fusion protein that contains multiple N- and O-glycosylation sites 141:240 CTLA4-Ig is a highly glycosylated therapeutic fusion protein that contains multiple N- and O-glycosylation sites. 25484062 1 14 contain contains 195:202 arg1 CTLA4-Ig 129:136 CTLA4-Ig 129:136 CTLA4-Ig 129:136 CTLA4-Ig is a highly glycosylated therapeutic fusion protein that contains multiple N- and O-glycosylation sites. 25484062 1 14 contain contains 195:202 arg2 sites 236:240 multiple N- and O-glycosylation sites 204:240 multiple N- and O-glycosylation sites 204:240 CTLA4-Ig is a highly glycosylated therapeutic fusion protein that contains multiple N- and O-glycosylation sites. 25484062 4 15 theme subsequent 746:755 arg1 development 757:767 subsequent development 746:767 subsequent development 746:767 Because of the limited clinical experience with biosimilars before approval, a comprehensive level of knowledge about the biosimilar candidates is needed to achieve subsequent development. 25484062 3 16 theme biosimilar 372:381 arg1 program 395:401 a CTLA4-Ig biosimilar development program 361:401 a CTLA4-Ig biosimilar development program 361:401 For a CTLA4-Ig biosimilar development program, comparative analytical data, especially the glycosylation data, can influence decisions about the type and amount of animal and clinical data needed to establish biosimilarity. 25484062 5 17 theme mapping 988:994 arg1 analysis 996:1003 peptide mapping analysis 980:1003 peptide mapping analysis 980:1003 Liquid chromatography-mass spectrometry (LC-MS) is a versatile technique for characterizing N- and O-glycosylation modification of recombinant therapeutic proteins, including 3 levels: intact protein analysis, peptide mapping analysis, and released glycans analysis. 25484062 5 17 theme mapping 988:994 arg1 levels 947:952 3 levels 945:952 3 levels: intact protein analysis, peptide mapping analysis, and released glycans analysis 945:1034 Liquid chromatography-mass spectrometry (LC-MS) is a versatile technique for characterizing N- and O-glycosylation modification of recombinant therapeutic proteins, including 3 levels: intact protein analysis, peptide mapping analysis, and released glycans analysis. 25484062 5 18 dep N- 862:863 arg1 modification 885:896 modification 885:896 modification 885:896 Liquid chromatography-mass spectrometry (LC-MS) is a versatile technique for characterizing N- and O-glycosylation modification of recombinant therapeutic proteins, including 3 levels: intact protein analysis, peptide mapping analysis, and released glycans analysis. 25484062 5 19 theme proteins 925:932 arg1 N- 862:863 N- 862:863 N- 862:863 Liquid chromatography-mass spectrometry (LC-MS) is a versatile technique for characterizing N- and O-glycosylation modification of recombinant therapeutic proteins, including 3 levels: intact protein analysis, peptide mapping analysis, and released glycans analysis. 25484062 5 19 theme proteins 925:932 arg1 O-glycosylation 869:883 O-glycosylation 869:883 O-glycosylation 869:883 Liquid chromatography-mass spectrometry (LC-MS) is a versatile technique for characterizing N- and O-glycosylation modification of recombinant therapeutic proteins, including 3 levels: intact protein analysis, peptide mapping analysis, and released glycans analysis. 25484062 2 20 theme serum 310:314 arg1 half-life 316:324 serum half-life 310:324 serum half-life 310:324 Glycosylation plays a vital role in protein solubility, stability, serum half-life, activity, and immunogenicity. 25484062 7 21 theme accurate 1407:1414 arg1 measurement 1428:1438 accurate intact mass measurement 1407:1438 accurate intact mass measurement 1407:1438 As the results show, the approach provides a set of routine tools that combine accurate intact mass measurement, peptide mapping, and released glycan profiling. 25484062 1 22 theme multiple 204:211 arg1 sites 236:240 multiple N- and O-glycosylation sites 204:240 multiple N- and O-glycosylation sites 204:240 CTLA4-Ig is a highly glycosylated therapeutic fusion protein that contains multiple N- and O-glycosylation sites. 25484062 3 23 theme development 383:393 arg1 program 395:401 a CTLA4-Ig biosimilar development program 361:401 a CTLA4-Ig biosimilar development program 361:401 For a CTLA4-Ig biosimilar development program, comparative analytical data, especially the glycosylation data, can influence decisions about the type and amount of animal and clinical data needed to establish biosimilarity. 25484062 8 24 theme future 1609:1614 arg1 studies 1616:1622 future studies 1609:1622 future studies addressing the similarity of CTLA4-Ig biosimilars 1609:1672 This approach can be used to comprehensively research a candidate biosimilar Fc-fusion protein and provides a basis for future studies addressing the similarity of CTLA4-Ig biosimilars. 25484062 1 25 theme N- 213:214 arg1 sites 236:240 multiple N- and O-glycosylation sites 204:240 multiple N- and O-glycosylation sites 204:240 CTLA4-Ig is a highly glycosylated therapeutic fusion protein that contains multiple N- and O-glycosylation sites. 25484062 0 26 from modification 44:55 arg1 proteins 76:83 CTLA4-Ig fusion proteins 60:83 CTLA4-Ig fusion proteins 60:83 Versatile characterization of glycosylation modification in CTLA4-Ig fusion proteins by liquid chromatography-mass spectrometry. 25484062 5 27 theme released 1010:1017 arg1 analysis 1027:1034 released glycans analysis 1010:1034 released glycans analysis 1010:1034 Liquid chromatography-mass spectrometry (LC-MS) is a versatile technique for characterizing N- and O-glycosylation modification of recombinant therapeutic proteins, including 3 levels: intact protein analysis, peptide mapping analysis, and released glycans analysis. 25484062 5 27 theme released 1010:1017 arg1 levels 947:952 3 levels 945:952 3 levels: intact protein analysis, peptide mapping analysis, and released glycans analysis 945:1034 Liquid chromatography-mass spectrometry (LC-MS) is a versatile technique for characterizing N- and O-glycosylation modification of recombinant therapeutic proteins, including 3 levels: intact protein analysis, peptide mapping analysis, and released glycans analysis. 25484062 7 28 theme routine 1380:1386 arg1 tools 1388:1392 routine tools 1380:1392 routine tools 1380:1392 As the results show, the approach provides a set of routine tools that combine accurate intact mass measurement, peptide mapping, and released glycan profiling. 25484062 0 29 theme Versatile 0:8 arg1 characterization 10:25 Versatile characterization 0:25 Versatile characterization of glycosylation modification in CTLA4-Ig fusion proteins by liquid chromatography-mass spectrometry. 0:127 Versatile characterization of glycosylation modification in CTLA4-Ig fusion proteins by liquid chromatography-mass spectrometry. 25484062 8 30 theme candidate 1545:1553 arg1 protein 1576:1582 a candidate biosimilar Fc-fusion protein 1543:1582 a candidate biosimilar Fc-fusion protein 1543:1582 This approach can be used to comprehensively research a candidate biosimilar Fc-fusion protein and provides a basis for future studies addressing the similarity of CTLA4-Ig biosimilars. 25484062 5 31 theme glycans 1019:1025 arg1 analysis 1027:1034 released glycans analysis 1010:1034 released glycans analysis 1010:1034 Liquid chromatography-mass spectrometry (LC-MS) is a versatile technique for characterizing N- and O-glycosylation modification of recombinant therapeutic proteins, including 3 levels: intact protein analysis, peptide mapping analysis, and released glycans analysis. 25484062 5 31 theme glycans 1019:1025 arg1 levels 947:952 3 levels 945:952 3 levels: intact protein analysis, peptide mapping analysis, and released glycans analysis 945:1034 Liquid chromatography-mass spectrometry (LC-MS) is a versatile technique for characterizing N- and O-glycosylation modification of recombinant therapeutic proteins, including 3 levels: intact protein analysis, peptide mapping analysis, and released glycans analysis. 25484062 6 32 used used 1254:1257 arg2 dissociation 1232:1243 electron-transfer dissociation 1214:1243 electron-transfer dissociation 1214:1243 In this report, an in-depth characterization of glycosylation of a candidate biosimilar was carried out using a systematic approach: N- and O-linked glycans were identified and electron-transfer dissociation was then used to pinpoint the 4 occupied O-glycosylation sites for the first time. 25484062 1 33 theme O-glycosylation 220:234 arg1 sites 236:240 multiple N- and O-glycosylation sites 204:240 multiple N- and O-glycosylation sites 204:240 CTLA4-Ig is a highly glycosylated therapeutic fusion protein that contains multiple N- and O-glycosylation sites. 25484062 0 34 theme glycosylation 30:42 arg1 modification 44:55 glycosylation modification 30:55 glycosylation modification in CTLA4-Ig fusion proteins 30:83 Versatile characterization of glycosylation modification in CTLA4-Ig fusion proteins by liquid chromatography-mass spectrometry. 25484062 6 35 theme occupied 1277:1284 arg1 sites 1302:1306 the 4 occupied O-glycosylation sites 1271:1306 the 4 occupied O-glycosylation sites for the first time 1271:1325 In this report, an in-depth characterization of glycosylation of a candidate biosimilar was carried out using a systematic approach: N- and O-linked glycans were identified and electron-transfer dissociation was then used to pinpoint the 4 occupied O-glycosylation sites for the first time. 25484062 7 36 theme peptide 1441:1447 arg1 mapping 1449:1455 peptide mapping 1441:1455 peptide mapping 1441:1455 As the results show, the approach provides a set of routine tools that combine accurate intact mass measurement, peptide mapping, and released glycan profiling. 25484062 5 37 theme therapeutic 913:923 arg1 levels 947:952 3 levels 945:952 3 levels: intact protein analysis, peptide mapping analysis, and released glycans analysis 945:1034 Liquid chromatography-mass spectrometry (LC-MS) is a versatile technique for characterizing N- and O-glycosylation modification of recombinant therapeutic proteins, including 3 levels: intact protein analysis, peptide mapping analysis, and released glycans analysis. 25484062 5 37 theme therapeutic 913:923 arg1 proteins 925:932 recombinant therapeutic proteins 901:932 recombinant therapeutic proteins 901:932 Liquid chromatography-mass spectrometry (LC-MS) is a versatile technique for characterizing N- and O-glycosylation modification of recombinant therapeutic proteins, including 3 levels: intact protein analysis, peptide mapping analysis, and released glycans analysis. 25484062 3 38 theme analytical 416:425 arg1 data 427:430 comparative analytical data 404:430 comparative analytical data 404:430 For a CTLA4-Ig biosimilar development program, comparative analytical data, especially the glycosylation data, can influence decisions about the type and amount of animal and clinical data needed to establish biosimilarity. 25484062 3 38 theme analytical 416:425 arg1 data 462:465 the glycosylation data 444:465 the glycosylation data 444:465 For a CTLA4-Ig biosimilar development program, comparative analytical data, especially the glycosylation data, can influence decisions about the type and amount of animal and clinical data needed to establish biosimilarity. 25484062 5 39 theme peptide 980:986 arg1 analysis 996:1003 peptide mapping analysis 980:1003 peptide mapping analysis 980:1003 Liquid chromatography-mass spectrometry (LC-MS) is a versatile technique for characterizing N- and O-glycosylation modification of recombinant therapeutic proteins, including 3 levels: intact protein analysis, peptide mapping analysis, and released glycans analysis. 25484062 5 39 theme peptide 980:986 arg1 levels 947:952 3 levels 945:952 3 levels: intact protein analysis, peptide mapping analysis, and released glycans analysis 945:1034 Liquid chromatography-mass spectrometry (LC-MS) is a versatile technique for characterizing N- and O-glycosylation modification of recombinant therapeutic proteins, including 3 levels: intact protein analysis, peptide mapping analysis, and released glycans analysis. 25484062 5 40 theme protein 962:968 arg1 levels 947:952 3 levels 945:952 3 levels: intact protein analysis, peptide mapping analysis, and released glycans analysis 945:1034 Liquid chromatography-mass spectrometry (LC-MS) is a versatile technique for characterizing N- and O-glycosylation modification of recombinant therapeutic proteins, including 3 levels: intact protein analysis, peptide mapping analysis, and released glycans analysis. 25484062 5 40 theme protein 962:968 arg1 analysis 970:977 intact protein analysis 955:977 intact protein analysis 955:977 Liquid chromatography-mass spectrometry (LC-MS) is a versatile technique for characterizing N- and O-glycosylation modification of recombinant therapeutic proteins, including 3 levels: intact protein analysis, peptide mapping analysis, and released glycans analysis. 25484062 3 41 theme glycosylation 448:460 arg1 data 427:430 comparative analytical data 404:430 comparative analytical data 404:430 For a CTLA4-Ig biosimilar development program, comparative analytical data, especially the glycosylation data, can influence decisions about the type and amount of animal and clinical data needed to establish biosimilarity. 25484062 3 41 theme glycosylation 448:460 arg1 data 462:465 the glycosylation data 444:465 the glycosylation data 444:465 For a CTLA4-Ig biosimilar development program, comparative analytical data, especially the glycosylation data, can influence decisions about the type and amount of animal and clinical data needed to establish biosimilarity. 25484062 8 42 used used 1510:1513 arg2 approach 1494:1501 This approach 1489:1501 This approach 1489:1501 This approach can be used to comprehensively research a candidate biosimilar Fc-fusion protein and provides a basis for future studies addressing the similarity of CTLA4-Ig biosimilars. 25484062 5 43 theme Liquid 770:775 arg1 LC-MS 811:815 LC-MS 811:815 LC-MS 811:815 Liquid chromatography-mass spectrometry (LC-MS) is a versatile technique for characterizing N- and O-glycosylation modification of recombinant therapeutic proteins, including 3 levels: intact protein analysis, peptide mapping analysis, and released glycans analysis. 25484062 5 43 theme Liquid 770:775 arg1 spectrometry 797:808 Liquid chromatography-mass spectrometry 770:808 Liquid chromatography-mass spectrometry (LC-MS) 770:816 Liquid chromatography-mass spectrometry (LC-MS) is a versatile technique for characterizing N- and O-glycosylation modification of recombinant therapeutic proteins, including 3 levels: intact protein analysis, peptide mapping analysis, and released glycans analysis. 25484062 5 43 theme Liquid 770:775 arg1 technique 833:841 a versatile technique 821:841 a versatile technique for characterizing N- and O-glycosylation modification of recombinant therapeutic proteins, including 3 levels: intact protein analysis, peptide mapping analysis, and released glycans analysis 821:1034 Liquid chromatography-mass spectrometry (LC-MS) is a versatile technique for characterizing N- and O-glycosylation modification of recombinant therapeutic proteins, including 3 levels: intact protein analysis, peptide mapping analysis, and released glycans analysis. 25484062 5 44 theme chromatography-mass 777:795 arg1 LC-MS 811:815 LC-MS 811:815 LC-MS 811:815 Liquid chromatography-mass spectrometry (LC-MS) is a versatile technique for characterizing N- and O-glycosylation modification of recombinant therapeutic proteins, including 3 levels: intact protein analysis, peptide mapping analysis, and released glycans analysis. 25484062 5 44 theme chromatography-mass 777:795 arg1 spectrometry 797:808 Liquid chromatography-mass spectrometry 770:808 Liquid chromatography-mass spectrometry (LC-MS) 770:816 Liquid chromatography-mass spectrometry (LC-MS) is a versatile technique for characterizing N- and O-glycosylation modification of recombinant therapeutic proteins, including 3 levels: intact protein analysis, peptide mapping analysis, and released glycans analysis. 25484062 5 44 theme chromatography-mass 777:795 arg1 technique 833:841 a versatile technique 821:841 a versatile technique for characterizing N- and O-glycosylation modification of recombinant therapeutic proteins, including 3 levels: intact protein analysis, peptide mapping analysis, and released glycans analysis 821:1034 Liquid chromatography-mass spectrometry (LC-MS) is a versatile technique for characterizing N- and O-glycosylation modification of recombinant therapeutic proteins, including 3 levels: intact protein analysis, peptide mapping analysis, and released glycans analysis. 25484062 5 45 theme intact 955:960 arg1 levels 947:952 3 levels 945:952 3 levels: intact protein analysis, peptide mapping analysis, and released glycans analysis 945:1034 Liquid chromatography-mass spectrometry (LC-MS) is a versatile technique for characterizing N- and O-glycosylation modification of recombinant therapeutic proteins, including 3 levels: intact protein analysis, peptide mapping analysis, and released glycans analysis. 25484062 5 45 theme intact 955:960 arg1 analysis 970:977 intact protein analysis 955:977 intact protein analysis 955:977 Liquid chromatography-mass spectrometry (LC-MS) is a versatile technique for characterizing N- and O-glycosylation modification of recombinant therapeutic proteins, including 3 levels: intact protein analysis, peptide mapping analysis, and released glycans analysis. 25484062 0 46 theme modification 44:55 arg1 characterization 10:25 Versatile characterization 0:25 Versatile characterization of glycosylation modification in CTLA4-Ig fusion proteins by liquid chromatography-mass spectrometry. 0:127 Versatile characterization of glycosylation modification in CTLA4-Ig fusion proteins by liquid chromatography-mass spectrometry. 25484062 8 47 theme CTLA4-Ig 1653:1660 arg1 biosimilars 1662:1672 CTLA4-Ig biosimilars 1653:1672 CTLA4-Ig biosimilars 1653:1672 This approach can be used to comprehensively research a candidate biosimilar Fc-fusion protein and provides a basis for future studies addressing the similarity of CTLA4-Ig biosimilars. 25484062 1 48 gly glycosylated 150:161 arg1 protein 182:188 a highly glycosylated therapeutic fusion protein 141:188 a highly glycosylated therapeutic fusion protein that contains multiple N- and O-glycosylation sites 141:240 CTLA4-Ig is a highly glycosylated therapeutic fusion protein that contains multiple N- and O-glycosylation sites. 25484062 1 48 gly glycosylated 150:161 arg1 CTLA4-Ig 129:136 CTLA4-Ig 129:136 CTLA4-Ig 129:136 CTLA4-Ig is a highly glycosylated therapeutic fusion protein that contains multiple N- and O-glycosylation sites. 25484062 3 49 theme comparative 404:414 arg1 data 427:430 comparative analytical data 404:430 comparative analytical data 404:430 For a CTLA4-Ig biosimilar development program, comparative analytical data, especially the glycosylation data, can influence decisions about the type and amount of animal and clinical data needed to establish biosimilarity. 25484062 3 49 theme comparative 404:414 arg1 data 462:465 the glycosylation data 444:465 the glycosylation data 444:465 For a CTLA4-Ig biosimilar development program, comparative analytical data, especially the glycosylation data, can influence decisions about the type and amount of animal and clinical data needed to establish biosimilarity. 25484062 4 50 theme knowledge 683:691 arg1 level 674:678 a comprehensive level 658:678 a comprehensive level of knowledge about the biosimilar candidates 658:723 Because of the limited clinical experience with biosimilars before approval, a comprehensive level of knowledge about the biosimilar candidates is needed to achieve subsequent development. 25484062 0 51 theme fusion 69:74 arg1 proteins 76:83 CTLA4-Ig fusion proteins 60:83 CTLA4-Ig fusion proteins 60:83 Versatile characterization of glycosylation modification in CTLA4-Ig fusion proteins by liquid chromatography-mass spectrometry. 25484062 0 52 from proteins 76:83 arg1 characterization 10:25 Versatile characterization 0:25 Versatile characterization of glycosylation modification in CTLA4-Ig fusion proteins by liquid chromatography-mass spectrometry. 0:127 Versatile characterization of glycosylation modification in CTLA4-Ig fusion proteins by liquid chromatography-mass spectrometry. 25484062 2 53 theme vital 265:269 arg1 role 271:274 a vital role 263:274 a vital role 263:274 Glycosylation plays a vital role in protein solubility, stability, serum half-life, activity, and immunogenicity. 25484062 6 54 theme O-linked 1177:1184 arg1 glycans 1186:1192 O-linked glycans 1177:1192 O-linked glycans 1177:1192 In this report, an in-depth characterization of glycosylation of a candidate biosimilar was carried out using a systematic approach: N- and O-linked glycans were identified and electron-transfer dissociation was then used to pinpoint the 4 occupied O-glycosylation sites for the first time. 25484062 3 55 theme animal 521:526 arg1 data 541:544 animal and clinical data 521:544 animal and clinical data needed to establish biosimilarity 521:578 For a CTLA4-Ig biosimilar development program, comparative analytical data, especially the glycosylation data, can influence decisions about the type and amount of animal and clinical data needed to establish biosimilarity. 25484062 0 56 theme CTLA4-Ig 60:67 arg1 proteins 76:83 CTLA4-Ig fusion proteins 60:83 CTLA4-Ig fusion proteins 60:83 Versatile characterization of glycosylation modification in CTLA4-Ig fusion proteins by liquid chromatography-mass spectrometry. 25484062 6 57 theme first 1316:1320 arg1 time 1322:1325 the first time 1312:1325 the first time 1312:1325 In this report, an in-depth characterization of glycosylation of a candidate biosimilar was carried out using a systematic approach: N- and O-linked glycans were identified and electron-transfer dissociation was then used to pinpoint the 4 occupied O-glycosylation sites for the first time. 25484062 7 58 theme tools 1388:1392 arg1 set 1373:1375 a set 1371:1375 a set of routine tools that combine accurate intact mass measurement, peptide mapping, and released glycan profiling 1371:1486 As the results show, the approach provides a set of routine tools that combine accurate intact mass measurement, peptide mapping, and released glycan profiling. 25484062 7 58 theme tools 1388:1392 arg1 tools 1388:1392 routine tools 1380:1392 routine tools 1380:1392 As the results show, the approach provides a set of routine tools that combine accurate intact mass measurement, peptide mapping, and released glycan profiling. 25484062 5 59 dep levels 947:952 arg1 analysis 1027:1034 released glycans analysis 1010:1034 released glycans analysis 1010:1034 Liquid chromatography-mass spectrometry (LC-MS) is a versatile technique for characterizing N- and O-glycosylation modification of recombinant therapeutic proteins, including 3 levels: intact protein analysis, peptide mapping analysis, and released glycans analysis. 25484062 5 59 dep levels 947:952 arg1 analysis 996:1003 peptide mapping analysis 980:1003 peptide mapping analysis 980:1003 Liquid chromatography-mass spectrometry (LC-MS) is a versatile technique for characterizing N- and O-glycosylation modification of recombinant therapeutic proteins, including 3 levels: intact protein analysis, peptide mapping analysis, and released glycans analysis. 25484062 5 59 dep levels 947:952 arg1 analysis 970:977 intact protein analysis 955:977 intact protein analysis 955:977 Liquid chromatography-mass spectrometry (LC-MS) is a versatile technique for characterizing N- and O-glycosylation modification of recombinant therapeutic proteins, including 3 levels: intact protein analysis, peptide mapping analysis, and released glycans analysis. 25484062 5 59 dep levels 947:952 arg1 levels 947:952 3 levels 945:952 3 levels: intact protein analysis, peptide mapping analysis, and released glycans analysis 945:1034 Liquid chromatography-mass spectrometry (LC-MS) is a versatile technique for characterizing N- and O-glycosylation modification of recombinant therapeutic proteins, including 3 levels: intact protein analysis, peptide mapping analysis, and released glycans analysis. 25484062 8 60 theme biosimilars 1662:1672 arg1 similarity 1639:1648 the similarity 1635:1648 the similarity of CTLA4-Ig biosimilars 1635:1672 This approach can be used to comprehensively research a candidate biosimilar Fc-fusion protein and provides a basis for future studies addressing the similarity of CTLA4-Ig biosimilars. 25484062 7 61 theme intact 1416:1421 arg1 measurement 1428:1438 accurate intact mass measurement 1407:1438 accurate intact mass measurement 1407:1438 As the results show, the approach provides a set of routine tools that combine accurate intact mass measurement, peptide mapping, and released glycan profiling. 25484062 7 62 theme mass 1423:1426 arg1 measurement 1428:1438 accurate intact mass measurement 1407:1438 accurate intact mass measurement 1407:1438 As the results show, the approach provides a set of routine tools that combine accurate intact mass measurement, peptide mapping, and released glycan profiling. 25484062 5 63 gly O-glycosylation 869:883 arg1 levels 947:952 3 levels 945:952 3 levels: intact protein analysis, peptide mapping analysis, and released glycans analysis 945:1034 Liquid chromatography-mass spectrometry (LC-MS) is a versatile technique for characterizing N- and O-glycosylation modification of recombinant therapeutic proteins, including 3 levels: intact protein analysis, peptide mapping analysis, and released glycans analysis. 25484062 5 63 gly O-glycosylation 869:883 arg1 proteins 925:932 recombinant therapeutic proteins 901:932 recombinant therapeutic proteins 901:932 Liquid chromatography-mass spectrometry (LC-MS) is a versatile technique for characterizing N- and O-glycosylation modification of recombinant therapeutic proteins, including 3 levels: intact protein analysis, peptide mapping analysis, and released glycans analysis. 25484062 1 64 theme glycosylated 150:161 arg1 protein 182:188 a highly glycosylated therapeutic fusion protein 141:188 a highly glycosylated therapeutic fusion protein that contains multiple N- and O-glycosylation sites 141:240 CTLA4-Ig is a highly glycosylated therapeutic fusion protein that contains multiple N- and O-glycosylation sites. 25484062 1 64 theme glycosylated 150:161 arg1 CTLA4-Ig 129:136 CTLA4-Ig 129:136 CTLA4-Ig 129:136 CTLA4-Ig is a highly glycosylated therapeutic fusion protein that contains multiple N- and O-glycosylation sites. 25484062 6 65 theme candidate 1104:1112 arg1 biosimilar 1114:1123 a candidate biosimilar 1102:1123 a candidate biosimilar 1102:1123 In this report, an in-depth characterization of glycosylation of a candidate biosimilar was carried out using a systematic approach: N- and O-linked glycans were identified and electron-transfer dissociation was then used to pinpoint the 4 occupied O-glycosylation sites for the first time. 25484062 6 66 link O-linked 1177:1184 arg1 glycans 1186:1192 O-linked glycans 1177:1192 O-linked glycans 1177:1192 In this report, an in-depth characterization of glycosylation of a candidate biosimilar was carried out using a systematic approach: N- and O-linked glycans were identified and electron-transfer dissociation was then used to pinpoint the 4 occupied O-glycosylation sites for the first time. 25484062 5 67 theme recombinant 901:911 arg1 levels 947:952 3 levels 945:952 3 levels: intact protein analysis, peptide mapping analysis, and released glycans analysis 945:1034 Liquid chromatography-mass spectrometry (LC-MS) is a versatile technique for characterizing N- and O-glycosylation modification of recombinant therapeutic proteins, including 3 levels: intact protein analysis, peptide mapping analysis, and released glycans analysis. 25484062 5 67 theme recombinant 901:911 arg1 proteins 925:932 recombinant therapeutic proteins 901:932 recombinant therapeutic proteins 901:932 Liquid chromatography-mass spectrometry (LC-MS) is a versatile technique for characterizing N- and O-glycosylation modification of recombinant therapeutic proteins, including 3 levels: intact protein analysis, peptide mapping analysis, and released glycans analysis. 25484062 8 68 theme Fc-fusion 1566:1574 arg1 protein 1576:1582 a candidate biosimilar Fc-fusion protein 1543:1582 a candidate biosimilar Fc-fusion protein 1543:1582 This approach can be used to comprehensively research a candidate biosimilar Fc-fusion protein and provides a basis for future studies addressing the similarity of CTLA4-Ig biosimilars. 25484062 1 69 theme therapeutic 163:173 arg1 protein 182:188 a highly glycosylated therapeutic fusion protein 141:188 a highly glycosylated therapeutic fusion protein that contains multiple N- and O-glycosylation sites 141:240 CTLA4-Ig is a highly glycosylated therapeutic fusion protein that contains multiple N- and O-glycosylation sites. 25484062 1 69 theme therapeutic 163:173 arg1 CTLA4-Ig 129:136 CTLA4-Ig 129:136 CTLA4-Ig 129:136 CTLA4-Ig is a highly glycosylated therapeutic fusion protein that contains multiple N- and O-glycosylation sites. 25484062 6 70 gly O-glycosylation 1286:1300 arg2 4 1275:1275 4 1275:1275 4 1275:1275 In this report, an in-depth characterization of glycosylation of a candidate biosimilar was carried out using a systematic approach: N- and O-linked glycans were identified and electron-transfer dissociation was then used to pinpoint the 4 occupied O-glycosylation sites for the first time. 25484062 6 70 gly O-glycosylation 1286:1300 arg2 sites 1302:1306 the 4 occupied O-glycosylation sites 1271:1306 the 4 occupied O-glycosylation sites for the first time 1271:1325 In this report, an in-depth characterization of glycosylation of a candidate biosimilar was carried out using a systematic approach: N- and O-linked glycans were identified and electron-transfer dissociation was then used to pinpoint the 4 occupied O-glycosylation sites for the first time. 25484062 6 71 theme biosimilar 1114:1123 arg1 glycosylation 1085:1097 glycosylation 1085:1097 glycosylation of a candidate biosimilar 1085:1123 In this report, an in-depth characterization of glycosylation of a candidate biosimilar was carried out using a systematic approach: N- and O-linked glycans were identified and electron-transfer dissociation was then used to pinpoint the 4 occupied O-glycosylation sites for the first time. 25484062 3 72 dep type 502:505 arg1 the 498:500 the 498:500 the 498:500 For a CTLA4-Ig biosimilar development program, comparative analytical data, especially the glycosylation data, can influence decisions about the type and amount of animal and clinical data needed to establish biosimilarity. 25484062 1 73 theme fusion 175:180 arg1 protein 182:188 a highly glycosylated therapeutic fusion protein 141:188 a highly glycosylated therapeutic fusion protein that contains multiple N- and O-glycosylation sites 141:240 CTLA4-Ig is a highly glycosylated therapeutic fusion protein that contains multiple N- and O-glycosylation sites. 25484062 1 73 theme fusion 175:180 arg1 CTLA4-Ig 129:136 CTLA4-Ig 129:136 CTLA4-Ig 129:136 CTLA4-Ig is a highly glycosylated therapeutic fusion protein that contains multiple N- and O-glycosylation sites. 25484062 6 74 theme systematic 1149:1158 arg1 approach 1160:1167 a systematic approach 1147:1167 a systematic approach 1147:1167 In this report, an in-depth characterization of glycosylation of a candidate biosimilar was carried out using a systematic approach: N- and O-linked glycans were identified and electron-transfer dissociation was then used to pinpoint the 4 occupied O-glycosylation sites for the first time. 25484062 4 75 theme comprehensive 660:672 arg1 level 674:678 a comprehensive level 658:678 a comprehensive level of knowledge about the biosimilar candidates 658:723 Because of the limited clinical experience with biosimilars before approval, a comprehensive level of knowledge about the biosimilar candidates is needed to achieve subsequent development. 25484062 3 76 theme CTLA4-Ig 363:370 arg1 program 395:401 a CTLA4-Ig biosimilar development program 361:401 a CTLA4-Ig biosimilar development program 361:401 For a CTLA4-Ig biosimilar development program, comparative analytical data, especially the glycosylation data, can influence decisions about the type and amount of animal and clinical data needed to establish biosimilarity. 25484062 6 77 theme electron-transfer 1214:1230 arg1 dissociation 1232:1243 electron-transfer dissociation 1214:1243 electron-transfer dissociation 1214:1243 In this report, an in-depth characterization of glycosylation of a candidate biosimilar was carried out using a systematic approach: N- and O-linked glycans were identified and electron-transfer dissociation was then used to pinpoint the 4 occupied O-glycosylation sites for the first time. 25484062 2 78 theme protein 279:285 arg1 solubility 287:296 protein solubility 279:296 protein solubility 279:296 Glycosylation plays a vital role in protein solubility, stability, serum half-life, activity, and immunogenicity. 25484062 6 79 gly glycosylation 1085:1097 arg1 biosimilar 1114:1123 a candidate biosimilar 1102:1123 a candidate biosimilar 1102:1123 In this report, an in-depth characterization of glycosylation of a candidate biosimilar was carried out using a systematic approach: N- and O-linked glycans were identified and electron-transfer dissociation was then used to pinpoint the 4 occupied O-glycosylation sites for the first time. 25484062 7 80 theme released 1462:1469 arg1 profiling 1478:1486 released glycan profiling 1462:1486 released glycan profiling 1462:1486 As the results show, the approach provides a set of routine tools that combine accurate intact mass measurement, peptide mapping, and released glycan profiling. 25484062 6 81 theme glycosylation 1085:1097 arg1 characterization 1065:1080 an in-depth characterization 1053:1080 an in-depth characterization of glycosylation of a candidate biosimilar 1053:1123 In this report, an in-depth characterization of glycosylation of a candidate biosimilar was carried out using a systematic approach: N- and O-linked glycans were identified and electron-transfer dissociation was then used to pinpoint the 4 occupied O-glycosylation sites for the first time. 24495382 3 0 theme many 580:583 arg1 process 596:602 many biological process 580:602 many biological process including signal transduction, cell-cell communication, and the immune response 580:682 Membrane proteins and their N-linked glycosylation mediate this microglial activation and regulate many biological process including signal transduction, cell-cell communication, and the immune response. 24495382 6 1 theme novel 1306:1310 arg1 sites 1328:1332 novel N-glycosylation sites 1306:1332 novel N-glycosylation sites 1306:1332 We identified 6928 proteins including 2850 membrane proteins and 1450 distinct N-glycosylation sites on 760 N-glycoproteins, of which 556 were considered novel N-glycosylation sites. 24495382 10 2 dep first 1831:1835 arg1 proteomic 1862:1870 proteomic 1862:1870 proteomic 1862:1870 To our knowledge, this workflow helped us to obtain the first and the largest membrane proteomic and N-glycoproteomic datesets for mouse microglia. 24495382 11 3 theme proteome 2032:2039 arg1 knowledge 2006:2014 the knowledge 2002:2014 the knowledge of the membrane proteome and N-glycoproteome expressed in microglia within the brain 2002:2099 Collectively, our proteomics and bioinformatics analysis significantly expands the knowledge of the membrane proteome and N-glycoproteome expressed in microglia within the brain and constitutes a foundation for ongoing proteomic studies and drug development for various neurological diseases. 24495382 1 4 theme processes 299:307 arg1 mediators 244:252 important cellular mediators 225:252 important cellular mediators of the immune response and neuroinflammatory processes 225:307 BACKGROUND: Microglial cells are resident macrophages of the central nervous system and important cellular mediators of the immune response and neuroinflammatory processes. 24495382 1 4 theme processes 299:307 arg1 BACKGROUND 137:146 BACKGROUND 137:146 BACKGROUND: Microglial cells are resident macrophages of the central nervous system and important cellular mediators of the immune response and neuroinflammatory processes. 137:308 BACKGROUND: Microglial cells are resident macrophages of the central nervous system and important cellular mediators of the immune response and neuroinflammatory processes. 24495382 1 4 theme processes 299:307 arg1 cells 160:164 Microglial cells 149:164 Microglial cells 149:164 BACKGROUND: Microglial cells are resident macrophages of the central nervous system and important cellular mediators of the immune response and neuroinflammatory processes. 24495382 1 4 theme processes 299:307 arg1 macrophages 179:189 resident macrophages 170:189 resident macrophages of the central nervous system 170:219 BACKGROUND: Microglial cells are resident macrophages of the central nervous system and important cellular mediators of the immune response and neuroinflammatory processes. 24495382 3 5 theme signal 614:619 arg1 transduction 621:632 signal transduction 614:632 signal transduction 614:632 Membrane proteins and their N-linked glycosylation mediate this microglial activation and regulate many biological process including signal transduction, cell-cell communication, and the immune response. 24495382 4 6 theme target 768:773 arg1 source 753:758 a valuable source 742:758 a valuable source of drug target and biomarker discovery 742:797 Although membrane proteins and N-glycosylation represent a valuable source of drug target and biomarker discovery, the knowledge of their expressed proteome in microglia is very limited. 24495382 1 7 theme nervous 206:212 arg1 system 214:219 the central nervous system 194:219 the central nervous system 194:219 BACKGROUND: Microglial cells are resident macrophages of the central nervous system and important cellular mediators of the immune response and neuroinflammatory processes. 24495382 7 8 from analysis 1402:1409 arg1 conditions 1421:1430 normal conditions 1414:1430 normal conditions of microglia for the first time 1414:1462 Especially, a total of 114 CD antigens are identified via MS-based analysis in normal conditions of microglia for the first time. 24495382 2 9 theme microglial 325:334 arg1 activation 336:345 microglial activation 325:345 microglial activation 325:345 In particular, microglial activation and communication between microglia, astrocytes, and neurons are hallmarks of the pathogenesis of several neurodegenerative diseases. 24495382 2 9 theme microglial 325:334 arg1 hallmarks 412:420 hallmarks 412:420 hallmarks of the pathogenesis of several neurodegenerative diseases 412:478 In particular, microglial activation and communication between microglia, astrocytes, and neurons are hallmarks of the pathogenesis of several neurodegenerative diseases. 24495382 2 9 theme microglial 325:334 arg1 communication 351:363 communication 351:363 communication between microglia, astrocytes, and neurons 351:406 In particular, microglial activation and communication between microglia, astrocytes, and neurons are hallmarks of the pathogenesis of several neurodegenerative diseases. 24495382 4 10 theme valuable 744:751 arg1 source 753:758 a valuable source 742:758 a valuable source of drug target and biomarker discovery 742:797 Although membrane proteins and N-glycosylation represent a valuable source of drug target and biomarker discovery, the knowledge of their expressed proteome in microglia is very limited. 24495382 11 11 theme proteomic 2142:2150 arg1 studies 2152:2158 ongoing proteomic studies 2134:2158 ongoing proteomic studies 2134:2158 Collectively, our proteomics and bioinformatics analysis significantly expands the knowledge of the membrane proteome and N-glycoproteome expressed in microglia within the brain and constitutes a foundation for ongoing proteomic studies and drug development for various neurological diseases. 24495382 5 12 theme membrane 936:943 arg1 proteome 945:952 a membrane proteome 934:952 a membrane proteome 934:952 RESULTS: To generate a large-scale repository, we constructed a membrane proteome and N-glycoproteome from BV-2 mouse microglia using a novel integrated approach, comprising of crude membrane fractionation, multienzyme-digestion FASP, N-glyco-FASP, and various mass spectrometry. 24495382 6 13 theme distinct 1222:1229 arg1 sites 1247:1251 1450 distinct N-glycosylation sites 1217:1251 1450 distinct N-glycosylation sites on 760 N-glycoproteins 1217:1274 We identified 6928 proteins including 2850 membrane proteins and 1450 distinct N-glycosylation sites on 760 N-glycoproteins, of which 556 were considered novel N-glycosylation sites. 24495382 3 14 theme immune 668:673 arg1 response 675:682 the immune response 664:682 the immune response 664:682 Membrane proteins and their N-linked glycosylation mediate this microglial activation and regulate many biological process including signal transduction, cell-cell communication, and the immune response. 24495382 5 15 theme novel 1008:1012 arg1 approach 1025:1032 a novel integrated approach 1006:1032 a novel integrated approach 1006:1032 RESULTS: To generate a large-scale repository, we constructed a membrane proteome and N-glycoproteome from BV-2 mouse microglia using a novel integrated approach, comprising of crude membrane fractionation, multienzyme-digestion FASP, N-glyco-FASP, and various mass spectrometry. 24495382 11 16 theme neurological 2193:2204 arg1 diseases 2206:2213 various neurological diseases 2185:2213 various neurological diseases 2185:2213 Collectively, our proteomics and bioinformatics analysis significantly expands the knowledge of the membrane proteome and N-glycoproteome expressed in microglia within the brain and constitutes a foundation for ongoing proteomic studies and drug development for various neurological diseases. 24495382 1 17 theme Microglial 149:158 arg1 BACKGROUND 137:146 BACKGROUND 137:146 BACKGROUND: Microglial cells are resident macrophages of the central nervous system and important cellular mediators of the immune response and neuroinflammatory processes. 137:308 BACKGROUND: Microglial cells are resident macrophages of the central nervous system and important cellular mediators of the immune response and neuroinflammatory processes. 24495382 1 17 theme Microglial 149:158 arg1 cells 160:164 Microglial cells 149:164 Microglial cells 149:164 BACKGROUND: Microglial cells are resident macrophages of the central nervous system and important cellular mediators of the immune response and neuroinflammatory processes. 24495382 1 17 theme Microglial 149:158 arg1 macrophages 179:189 resident macrophages 170:189 resident macrophages of the central nervous system 170:219 BACKGROUND: Microglial cells are resident macrophages of the central nervous system and important cellular mediators of the immune response and neuroinflammatory processes. 24495382 8 18 theme immune 1610:1615 arg1 responses 1617:1625 immune responses 1610:1625 immune responses 1610:1625 Our bioinformatics analysis provides a rich proteomic resource for examining microglial function in, for example, cell-to-cell communication and immune responses. 24495382 4 19 theme biomarker 779:787 arg1 discovery 789:797 drug target and biomarker discovery 763:797 discovery 789:797 Although membrane proteins and N-glycosylation represent a valuable source of drug target and biomarker discovery, the knowledge of their expressed proteome in microglia is very limited. 24495382 0 20 theme BV-2 65:68 arg1 microglia 76:84 BV-2 mouse microglia 65:84 BV-2 mouse microglia 65:84 Characterization of the membrane proteome and N-glycoproteome in BV-2 mouse microglia by liquid chromatography-tandem mass spectrometry. 24495382 5 21 theme mouse 984:988 arg1 microglia 990:998 BV-2 mouse microglia 979:998 BV-2 mouse microglia 979:998 RESULTS: To generate a large-scale repository, we constructed a membrane proteome and N-glycoproteome from BV-2 mouse microglia using a novel integrated approach, comprising of crude membrane fractionation, multienzyme-digestion FASP, N-glyco-FASP, and various mass spectrometry. 24495382 5 22 from microglia 990:998 arg1 N-glycoproteome 958:972 N-glycoproteome 958:972 N-glycoproteome 958:972 RESULTS: To generate a large-scale repository, we constructed a membrane proteome and N-glycoproteome from BV-2 mouse microglia using a novel integrated approach, comprising of crude membrane fractionation, multienzyme-digestion FASP, N-glyco-FASP, and various mass spectrometry. 24495382 5 22 from microglia 990:998 arg1 proteome 945:952 a membrane proteome 934:952 a membrane proteome 934:952 RESULTS: To generate a large-scale repository, we constructed a membrane proteome and N-glycoproteome from BV-2 mouse microglia using a novel integrated approach, comprising of crude membrane fractionation, multienzyme-digestion FASP, N-glyco-FASP, and various mass spectrometry. 24495382 0 23 from Characterization 0:15 arg1 microglia 76:84 BV-2 mouse microglia 65:84 BV-2 mouse microglia 65:84 Characterization of the membrane proteome and N-glycoproteome in BV-2 mouse microglia by liquid chromatography-tandem mass spectrometry. 24495382 10 24 theme largest 1845:1851 arg1 membrane 1853:1860 the largest membrane 1841:1860 the largest membrane 1841:1860 To our knowledge, this workflow helped us to obtain the first and the largest membrane proteomic and N-glycoproteomic datesets for mouse microglia. 24495382 0 25 theme liquid 89:94 arg1 spectrometry 123:134 liquid chromatography-tandem mass spectrometry 89:134 liquid chromatography-tandem mass spectrometry 89:134 Characterization of the membrane proteome and N-glycoproteome in BV-2 mouse microglia by liquid chromatography-tandem mass spectrometry. 24495382 9 26 theme integrated 1670:1679 arg1 approach 1691:1698 a novel integrated proteomic approach 1662:1698 a novel integrated proteomic approach for improved identification of membrane protein and N-glycosylation sites 1662:1772 CONCLUSIONS: Herein, we introduce a novel integrated proteomic approach for improved identification of membrane protein and N-glycosylation sites. 24495382 0 27 from N-glycoproteome 46:60 arg1 microglia 76:84 BV-2 mouse microglia 65:84 BV-2 mouse microglia 65:84 Characterization of the membrane proteome and N-glycoproteome in BV-2 mouse microglia by liquid chromatography-tandem mass spectrometry. 24495382 8 28 theme bioinformatics 1469:1482 arg1 analysis 1484:1491 Our bioinformatics analysis 1465:1491 Our bioinformatics analysis 1465:1491 Our bioinformatics analysis provides a rich proteomic resource for examining microglial function in, for example, cell-to-cell communication and immune responses. 24495382 2 29 theme pathogenesis 429:440 arg1 activation 336:345 microglial activation 325:345 microglial activation 325:345 In particular, microglial activation and communication between microglia, astrocytes, and neurons are hallmarks of the pathogenesis of several neurodegenerative diseases. 24495382 2 29 theme pathogenesis 429:440 arg1 hallmarks 412:420 hallmarks 412:420 hallmarks of the pathogenesis of several neurodegenerative diseases 412:478 In particular, microglial activation and communication between microglia, astrocytes, and neurons are hallmarks of the pathogenesis of several neurodegenerative diseases. 24495382 2 29 theme pathogenesis 429:440 arg1 communication 351:363 communication 351:363 communication between microglia, astrocytes, and neurons 351:406 In particular, microglial activation and communication between microglia, astrocytes, and neurons are hallmarks of the pathogenesis of several neurodegenerative diseases. 24495382 0 30 theme mass 118:121 arg1 spectrometry 123:134 liquid chromatography-tandem mass spectrometry 89:134 liquid chromatography-tandem mass spectrometry 89:134 Characterization of the membrane proteome and N-glycoproteome in BV-2 mouse microglia by liquid chromatography-tandem mass spectrometry. 24495382 5 31 theme multienzyme-digestion 1079:1099 arg1 FASP 1101:1104 multienzyme-digestion FASP 1079:1104 multienzyme-digestion FASP 1079:1104 RESULTS: To generate a large-scale repository, we constructed a membrane proteome and N-glycoproteome from BV-2 mouse microglia using a novel integrated approach, comprising of crude membrane fractionation, multienzyme-digestion FASP, N-glyco-FASP, and various mass spectrometry. 24495382 6 32 theme 2850 1190:1193 arg1 proteins 1204:1211 2850 membrane proteins 1190:1211 2850 membrane proteins 1190:1211 We identified 6928 proteins including 2850 membrane proteins and 1450 distinct N-glycosylation sites on 760 N-glycoproteins, of which 556 were considered novel N-glycosylation sites. 24495382 6 33 gly N-glycosylation 1231:1245 arg2 sites 1247:1251 1450 distinct N-glycosylation sites 1217:1251 1450 distinct N-glycosylation sites on 760 N-glycoproteins 1217:1274 We identified 6928 proteins including 2850 membrane proteins and 1450 distinct N-glycosylation sites on 760 N-glycoproteins, of which 556 were considered novel N-glycosylation sites. 24495382 6 33 gly N-glycosylation 1231:1245 arg2 1450 1217:1220 1450 1217:1220 1450 1217:1220 We identified 6928 proteins including 2850 membrane proteins and 1450 distinct N-glycosylation sites on 760 N-glycoproteins, of which 556 were considered novel N-glycosylation sites. 24495382 4 34 theme proteome 833:840 arg1 knowledge 804:812 the knowledge 800:812 the knowledge of their expressed proteome in microglia 800:853 Although membrane proteins and N-glycosylation represent a valuable source of drug target and biomarker discovery, the knowledge of their expressed proteome in microglia is very limited. 24495382 5 35 theme large-scale 895:905 arg1 repository 907:916 a large-scale repository 893:916 a large-scale repository 893:916 RESULTS: To generate a large-scale repository, we constructed a membrane proteome and N-glycoproteome from BV-2 mouse microglia using a novel integrated approach, comprising of crude membrane fractionation, multienzyme-digestion FASP, N-glyco-FASP, and various mass spectrometry. 24495382 9 36 theme improved 1704:1711 arg1 identification 1713:1726 improved identification 1704:1726 improved identification of membrane protein and N-glycosylation sites 1704:1772 CONCLUSIONS: Herein, we introduce a novel integrated proteomic approach for improved identification of membrane protein and N-glycosylation sites. 24495382 8 37 theme rich 1504:1507 arg1 resource 1519:1526 a rich proteomic resource 1502:1526 a rich proteomic resource for examining microglial function in 1502:1563 Our bioinformatics analysis provides a rich proteomic resource for examining microglial function in, for example, cell-to-cell communication and immune responses. 24495382 2 38 theme diseases 471:478 arg1 pathogenesis 429:440 the pathogenesis 425:440 the pathogenesis of several neurodegenerative diseases 425:478 In particular, microglial activation and communication between microglia, astrocytes, and neurons are hallmarks of the pathogenesis of several neurodegenerative diseases. 24495382 5 39 theme crude 1049:1053 arg1 fractionation 1064:1076 crude membrane fractionation 1049:1076 crude membrane fractionation 1049:1076 RESULTS: To generate a large-scale repository, we constructed a membrane proteome and N-glycoproteome from BV-2 mouse microglia using a novel integrated approach, comprising of crude membrane fractionation, multienzyme-digestion FASP, N-glyco-FASP, and various mass spectrometry. 24495382 2 40 theme several 445:451 arg1 diseases 471:478 several neurodegenerative diseases 445:478 several neurodegenerative diseases 445:478 In particular, microglial activation and communication between microglia, astrocytes, and neurons are hallmarks of the pathogenesis of several neurodegenerative diseases. 24495382 0 41 theme proteome 33:40 arg1 Characterization 0:15 Characterization 0:15 Characterization of the membrane proteome 0:40 Characterization of the membrane proteome and N-glycoproteome in BV-2 mouse microglia by liquid chromatography-tandem mass spectrometry. 24495382 0 41 theme proteome 33:40 arg1 N-glycoproteome 46:60 N-glycoproteome 46:60 N-glycoproteome in BV-2 mouse microglia 46:84 Characterization of the membrane proteome and N-glycoproteome in BV-2 mouse microglia by liquid chromatography-tandem mass spectrometry. 24495382 5 42 theme various 1125:1131 arg1 spectrometry 1138:1149 various mass spectrometry 1125:1149 various mass spectrometry 1125:1149 RESULTS: To generate a large-scale repository, we constructed a membrane proteome and N-glycoproteome from BV-2 mouse microglia using a novel integrated approach, comprising of crude membrane fractionation, multienzyme-digestion FASP, N-glyco-FASP, and various mass spectrometry. 24495382 7 43 theme normal 1414:1419 arg1 conditions 1421:1430 normal conditions 1414:1430 normal conditions of microglia for the first time 1414:1462 Especially, a total of 114 CD antigens are identified via MS-based analysis in normal conditions of microglia for the first time. 24495382 9 44 theme N-glycosylation 1752:1766 arg1 sites 1768:1772 N-glycosylation sites 1752:1772 N-glycosylation sites 1752:1772 CONCLUSIONS: Herein, we introduce a novel integrated proteomic approach for improved identification of membrane protein and N-glycosylation sites. 24495382 9 45 theme protein 1740:1746 arg1 identification 1713:1726 improved identification 1704:1726 improved identification of membrane protein and N-glycosylation sites 1704:1772 CONCLUSIONS: Herein, we introduce a novel integrated proteomic approach for improved identification of membrane protein and N-glycosylation sites. 24495382 10 46 theme first 1831:1835 arg1 datesets 1893:1900 the first and the largest membrane proteomic and N-glycoproteomic datesets 1827:1900 the first and the largest membrane proteomic and N-glycoproteomic datesets for mouse microglia 1827:1920 To our knowledge, this workflow helped us to obtain the first and the largest membrane proteomic and N-glycoproteomic datesets for mouse microglia. 24495382 10 47 theme N-glycoproteomic 1876:1891 arg1 datesets 1893:1900 the first and the largest membrane proteomic and N-glycoproteomic datesets 1827:1900 the first and the largest membrane proteomic and N-glycoproteomic datesets for mouse microglia 1827:1920 To our knowledge, this workflow helped us to obtain the first and the largest membrane proteomic and N-glycoproteomic datesets for mouse microglia. 24495382 6 48 theme N-glycosylation 1231:1245 arg1 sites 1247:1251 1450 distinct N-glycosylation sites 1217:1251 1450 distinct N-glycosylation sites on 760 N-glycoproteins 1217:1274 We identified 6928 proteins including 2850 membrane proteins and 1450 distinct N-glycosylation sites on 760 N-glycoproteins, of which 556 were considered novel N-glycosylation sites. 24495382 6 49 from proteins 1204:1211 arg1 N-glycoproteins 1260:1274 760 N-glycoproteins 1256:1274 760 N-glycoproteins 1256:1274 We identified 6928 proteins including 2850 membrane proteins and 1450 distinct N-glycosylation sites on 760 N-glycoproteins, of which 556 were considered novel N-glycosylation sites. 24495382 3 50 theme biological 585:594 arg1 process 596:602 many biological process 580:602 many biological process including signal transduction, cell-cell communication, and the immune response 580:682 Membrane proteins and their N-linked glycosylation mediate this microglial activation and regulate many biological process including signal transduction, cell-cell communication, and the immune response. 24495382 6 51 gly N-glycosylation 1312:1326 arg2 sites 1328:1332 novel N-glycosylation sites 1306:1332 novel N-glycosylation sites 1306:1332 We identified 6928 proteins including 2850 membrane proteins and 1450 distinct N-glycosylation sites on 760 N-glycoproteins, of which 556 were considered novel N-glycosylation sites. 24495382 10 52 theme membrane 1853:1860 arg1 datesets 1893:1900 the first and the largest membrane proteomic and N-glycoproteomic datesets 1827:1900 the first and the largest membrane proteomic and N-glycoproteomic datesets for mouse microglia 1827:1920 To our knowledge, this workflow helped us to obtain the first and the largest membrane proteomic and N-glycoproteomic datesets for mouse microglia. 24495382 1 53 theme response 268:275 arg1 mediators 244:252 important cellular mediators 225:252 important cellular mediators of the immune response and neuroinflammatory processes 225:307 BACKGROUND: Microglial cells are resident macrophages of the central nervous system and important cellular mediators of the immune response and neuroinflammatory processes. 24495382 1 53 theme response 268:275 arg1 BACKGROUND 137:146 BACKGROUND 137:146 BACKGROUND: Microglial cells are resident macrophages of the central nervous system and important cellular mediators of the immune response and neuroinflammatory processes. 137:308 BACKGROUND: Microglial cells are resident macrophages of the central nervous system and important cellular mediators of the immune response and neuroinflammatory processes. 24495382 1 53 theme response 268:275 arg1 cells 160:164 Microglial cells 149:164 Microglial cells 149:164 BACKGROUND: Microglial cells are resident macrophages of the central nervous system and important cellular mediators of the immune response and neuroinflammatory processes. 24495382 1 53 theme response 268:275 arg1 macrophages 179:189 resident macrophages 170:189 resident macrophages of the central nervous system 170:219 BACKGROUND: Microglial cells are resident macrophages of the central nervous system and important cellular mediators of the immune response and neuroinflammatory processes. 24495382 3 54 link N-linked 509:516 arg1 glycosylation 518:530 their N-linked glycosylation 503:530 their N-linked glycosylation 503:530 Membrane proteins and their N-linked glycosylation mediate this microglial activation and regulate many biological process including signal transduction, cell-cell communication, and the immune response. 24495382 7 55 theme CD 1362:1363 arg1 antigens 1365:1372 114 CD antigens 1358:1372 114 CD antigens 1358:1372 Especially, a total of 114 CD antigens are identified via MS-based analysis in normal conditions of microglia for the first time. 24495382 10 56 theme mouse 1906:1910 arg1 microglia 1912:1920 mouse microglia 1906:1920 mouse microglia 1906:1920 To our knowledge, this workflow helped us to obtain the first and the largest membrane proteomic and N-glycoproteomic datesets for mouse microglia. 24495382 1 57 theme neuroinflammatory 281:297 arg1 processes 299:307 neuroinflammatory processes 281:307 neuroinflammatory processes 281:307 BACKGROUND: Microglial cells are resident macrophages of the central nervous system and important cellular mediators of the immune response and neuroinflammatory processes. 24495382 1 58 theme central 198:204 arg1 system 214:219 the central nervous system 194:219 the central nervous system 194:219 BACKGROUND: Microglial cells are resident macrophages of the central nervous system and important cellular mediators of the immune response and neuroinflammatory processes. 24495382 4 59 theme drug 763:766 arg1 target 768:773 drug target and biomarker discovery 763:797 target 768:773 Although membrane proteins and N-glycosylation represent a valuable source of drug target and biomarker discovery, the knowledge of their expressed proteome in microglia is very limited. 24495382 6 60 gly N-glycoproteins 1260:1274 arg1 N-glycoproteins 1260:1274 760 N-glycoproteins 1256:1274 760 N-glycoproteins 1256:1274 We identified 6928 proteins including 2850 membrane proteins and 1450 distinct N-glycosylation sites on 760 N-glycoproteins, of which 556 were considered novel N-glycosylation sites. 24495382 11 61 theme bioinformatics 1956:1969 arg1 analysis 1971:1978 our proteomics and bioinformatics analysis 1937:1978 analysis 1971:1978 Collectively, our proteomics and bioinformatics analysis significantly expands the knowledge of the membrane proteome and N-glycoproteome expressed in microglia within the brain and constitutes a foundation for ongoing proteomic studies and drug development for various neurological diseases. 24495382 3 62 theme cell-cell 635:643 arg1 communication 645:657 cell-cell communication 635:657 cell-cell communication 635:657 Membrane proteins and their N-linked glycosylation mediate this microglial activation and regulate many biological process including signal transduction, cell-cell communication, and the immune response. 24495382 1 63 theme system 214:219 arg1 mediators 244:252 important cellular mediators 225:252 important cellular mediators of the immune response and neuroinflammatory processes 225:307 BACKGROUND: Microglial cells are resident macrophages of the central nervous system and important cellular mediators of the immune response and neuroinflammatory processes. 24495382 1 63 theme system 214:219 arg1 BACKGROUND 137:146 BACKGROUND 137:146 BACKGROUND: Microglial cells are resident macrophages of the central nervous system and important cellular mediators of the immune response and neuroinflammatory processes. 137:308 BACKGROUND: Microglial cells are resident macrophages of the central nervous system and important cellular mediators of the immune response and neuroinflammatory processes. 24495382 1 63 theme system 214:219 arg1 cells 160:164 Microglial cells 149:164 Microglial cells 149:164 BACKGROUND: Microglial cells are resident macrophages of the central nervous system and important cellular mediators of the immune response and neuroinflammatory processes. 24495382 1 63 theme system 214:219 arg1 macrophages 179:189 resident macrophages 170:189 resident macrophages of the central nervous system 170:219 BACKGROUND: Microglial cells are resident macrophages of the central nervous system and important cellular mediators of the immune response and neuroinflammatory processes. 24495382 11 64 theme ongoing 2134:2140 arg1 studies 2152:2158 ongoing proteomic studies 2134:2158 ongoing proteomic studies 2134:2158 Collectively, our proteomics and bioinformatics analysis significantly expands the knowledge of the membrane proteome and N-glycoproteome expressed in microglia within the brain and constitutes a foundation for ongoing proteomic studies and drug development for various neurological diseases. 24495382 1 65 theme important 225:233 arg1 mediators 244:252 important cellular mediators 225:252 important cellular mediators of the immune response and neuroinflammatory processes 225:307 BACKGROUND: Microglial cells are resident macrophages of the central nervous system and important cellular mediators of the immune response and neuroinflammatory processes. 24495382 1 65 theme important 225:233 arg1 BACKGROUND 137:146 BACKGROUND 137:146 BACKGROUND: Microglial cells are resident macrophages of the central nervous system and important cellular mediators of the immune response and neuroinflammatory processes. 137:308 BACKGROUND: Microglial cells are resident macrophages of the central nervous system and important cellular mediators of the immune response and neuroinflammatory processes. 24495382 8 66 theme cell-to-cell 1579:1590 arg1 communication 1592:1604 cell-to-cell communication 1579:1604 cell-to-cell communication 1579:1604 Our bioinformatics analysis provides a rich proteomic resource for examining microglial function in, for example, cell-to-cell communication and immune responses. 24495382 11 67 theme drug 2164:2167 arg1 development 2169:2179 drug development 2164:2179 drug development 2164:2179 Collectively, our proteomics and bioinformatics analysis significantly expands the knowledge of the membrane proteome and N-glycoproteome expressed in microglia within the brain and constitutes a foundation for ongoing proteomic studies and drug development for various neurological diseases. 24495382 5 68 theme integrated 1014:1023 arg1 approach 1025:1032 a novel integrated approach 1006:1032 a novel integrated approach 1006:1032 RESULTS: To generate a large-scale repository, we constructed a membrane proteome and N-glycoproteome from BV-2 mouse microglia using a novel integrated approach, comprising of crude membrane fractionation, multienzyme-digestion FASP, N-glyco-FASP, and various mass spectrometry. 24495382 9 69 theme novel 1664:1668 arg1 approach 1691:1698 a novel integrated proteomic approach 1662:1698 a novel integrated proteomic approach for improved identification of membrane protein and N-glycosylation sites 1662:1772 CONCLUSIONS: Herein, we introduce a novel integrated proteomic approach for improved identification of membrane protein and N-glycosylation sites. 24495382 0 70 theme mouse 70:74 arg1 microglia 76:84 BV-2 mouse microglia 65:84 BV-2 mouse microglia 65:84 Characterization of the membrane proteome and N-glycoproteome in BV-2 mouse microglia by liquid chromatography-tandem mass spectrometry. 24495382 5 71 theme BV-2 979:982 arg1 microglia 990:998 BV-2 mouse microglia 979:998 BV-2 mouse microglia 979:998 RESULTS: To generate a large-scale repository, we constructed a membrane proteome and N-glycoproteome from BV-2 mouse microglia using a novel integrated approach, comprising of crude membrane fractionation, multienzyme-digestion FASP, N-glyco-FASP, and various mass spectrometry. 24495382 6 72 theme N-glycosylation 1312:1326 arg1 sites 1328:1332 novel N-glycosylation sites 1306:1332 novel N-glycosylation sites 1306:1332 We identified 6928 proteins including 2850 membrane proteins and 1450 distinct N-glycosylation sites on 760 N-glycoproteins, of which 556 were considered novel N-glycosylation sites. 24495382 1 73 theme resident 170:177 arg1 BACKGROUND 137:146 BACKGROUND 137:146 BACKGROUND: Microglial cells are resident macrophages of the central nervous system and important cellular mediators of the immune response and neuroinflammatory processes. 137:308 BACKGROUND: Microglial cells are resident macrophages of the central nervous system and important cellular mediators of the immune response and neuroinflammatory processes. 24495382 1 73 theme resident 170:177 arg1 cells 160:164 Microglial cells 149:164 Microglial cells 149:164 BACKGROUND: Microglial cells are resident macrophages of the central nervous system and important cellular mediators of the immune response and neuroinflammatory processes. 24495382 1 73 theme resident 170:177 arg1 macrophages 179:189 resident macrophages 170:189 resident macrophages of the central nervous system 170:219 BACKGROUND: Microglial cells are resident macrophages of the central nervous system and important cellular mediators of the immune response and neuroinflammatory processes. 24495382 4 74 theme discovery 789:797 arg1 source 753:758 a valuable source 742:758 a valuable source of drug target and biomarker discovery 742:797 Although membrane proteins and N-glycosylation represent a valuable source of drug target and biomarker discovery, the knowledge of their expressed proteome in microglia is very limited. 24495382 0 75 theme chromatography-tandem 96:116 arg1 spectrometry 123:134 liquid chromatography-tandem mass spectrometry 89:134 liquid chromatography-tandem mass spectrometry 89:134 Characterization of the membrane proteome and N-glycoproteome in BV-2 mouse microglia by liquid chromatography-tandem mass spectrometry. 24495382 5 76 theme membrane 1055:1062 arg1 fractionation 1064:1076 crude membrane fractionation 1049:1076 crude membrane fractionation 1049:1076 RESULTS: To generate a large-scale repository, we constructed a membrane proteome and N-glycoproteome from BV-2 mouse microglia using a novel integrated approach, comprising of crude membrane fractionation, multienzyme-digestion FASP, N-glyco-FASP, and various mass spectrometry. 24495382 9 77 theme proteomic 1681:1689 arg1 approach 1691:1698 a novel integrated proteomic approach 1662:1698 a novel integrated proteomic approach for improved identification of membrane protein and N-glycosylation sites 1662:1772 CONCLUSIONS: Herein, we introduce a novel integrated proteomic approach for improved identification of membrane protein and N-glycosylation sites. 24495382 6 78 theme membrane 1195:1202 arg1 proteins 1204:1211 2850 membrane proteins 1190:1211 2850 membrane proteins 1190:1211 We identified 6928 proteins including 2850 membrane proteins and 1450 distinct N-glycosylation sites on 760 N-glycoproteins, of which 556 were considered novel N-glycosylation sites. 24495382 11 79 dep proteome 2032:2039 arg1 the 2019:2021 the 2019:2021 the 2019:2021 Collectively, our proteomics and bioinformatics analysis significantly expands the knowledge of the membrane proteome and N-glycoproteome expressed in microglia within the brain and constitutes a foundation for ongoing proteomic studies and drug development for various neurological diseases. 24495382 7 80 theme microglia 1435:1443 arg1 conditions 1421:1430 normal conditions 1414:1430 normal conditions of microglia for the first time 1414:1462 Especially, a total of 114 CD antigens are identified via MS-based analysis in normal conditions of microglia for the first time. 24495382 11 81 theme N-glycoproteome 2045:2059 arg1 knowledge 2006:2014 the knowledge 2002:2014 the knowledge of the membrane proteome and N-glycoproteome expressed in microglia within the brain 2002:2099 Collectively, our proteomics and bioinformatics analysis significantly expands the knowledge of the membrane proteome and N-glycoproteome expressed in microglia within the brain and constitutes a foundation for ongoing proteomic studies and drug development for various neurological diseases. 24495382 4 82 theme expressed 823:831 arg1 proteome 833:840 their expressed proteome 817:840 their expressed proteome 817:840 Although membrane proteins and N-glycosylation represent a valuable source of drug target and biomarker discovery, the knowledge of their expressed proteome in microglia is very limited. 24495382 3 83 theme Membrane 481:488 arg1 proteins 490:497 Membrane proteins 481:497 Membrane proteins 481:497 Membrane proteins and their N-linked glycosylation mediate this microglial activation and regulate many biological process including signal transduction, cell-cell communication, and the immune response. 24495382 0 84 theme membrane 24:31 arg1 proteome 33:40 the membrane proteome 20:40 the membrane proteome 20:40 Characterization of the membrane proteome and N-glycoproteome in BV-2 mouse microglia by liquid chromatography-tandem mass spectrometry. 24495382 6 85 theme 6928 1166:1169 arg1 sites 1247:1251 1450 distinct N-glycosylation sites 1217:1251 1450 distinct N-glycosylation sites on 760 N-glycoproteins 1217:1274 We identified 6928 proteins including 2850 membrane proteins and 1450 distinct N-glycosylation sites on 760 N-glycoproteins, of which 556 were considered novel N-glycosylation sites. 24495382 6 85 theme 6928 1166:1169 arg1 proteins 1204:1211 2850 membrane proteins 1190:1211 2850 membrane proteins 1190:1211 We identified 6928 proteins including 2850 membrane proteins and 1450 distinct N-glycosylation sites on 760 N-glycoproteins, of which 556 were considered novel N-glycosylation sites. 24495382 6 85 theme 6928 1166:1169 arg1 proteins 1171:1178 6928 proteins 1166:1178 6928 proteins including 2850 membrane proteins and 1450 distinct N-glycosylation sites on 760 N-glycoproteins, of which 556 were considered novel N-glycosylation sites 1166:1332 We identified 6928 proteins including 2850 membrane proteins and 1450 distinct N-glycosylation sites on 760 N-glycoproteins, of which 556 were considered novel N-glycosylation sites. 24495382 2 86 theme neurodegenerative 453:469 arg1 diseases 471:478 several neurodegenerative diseases 445:478 several neurodegenerative diseases 445:478 In particular, microglial activation and communication between microglia, astrocytes, and neurons are hallmarks of the pathogenesis of several neurodegenerative diseases. 24495382 9 87 theme membrane 1731:1738 arg1 protein 1740:1746 membrane protein 1731:1746 membrane protein 1731:1746 CONCLUSIONS: Herein, we introduce a novel integrated proteomic approach for improved identification of membrane protein and N-glycosylation sites. 24495382 8 88 theme proteomic 1509:1517 arg1 resource 1519:1526 a rich proteomic resource 1502:1526 a rich proteomic resource for examining microglial function in 1502:1563 Our bioinformatics analysis provides a rich proteomic resource for examining microglial function in, for example, cell-to-cell communication and immune responses. 24495382 6 89 from sites 1247:1251 arg1 N-glycoproteins 1260:1274 760 N-glycoproteins 1256:1274 760 N-glycoproteins 1256:1274 We identified 6928 proteins including 2850 membrane proteins and 1450 distinct N-glycosylation sites on 760 N-glycoproteins, of which 556 were considered novel N-glycosylation sites. 24495382 3 90 theme N-linked 509:516 arg1 glycosylation 518:530 their N-linked glycosylation 503:530 their N-linked glycosylation 503:530 Membrane proteins and their N-linked glycosylation mediate this microglial activation and regulate many biological process including signal transduction, cell-cell communication, and the immune response. 24495382 5 91 theme mass 1133:1136 arg1 spectrometry 1138:1149 various mass spectrometry 1125:1149 various mass spectrometry 1125:1149 RESULTS: To generate a large-scale repository, we constructed a membrane proteome and N-glycoproteome from BV-2 mouse microglia using a novel integrated approach, comprising of crude membrane fractionation, multienzyme-digestion FASP, N-glyco-FASP, and various mass spectrometry. 24495382 2 92 from hallmarks 412:420 arg1 particular 313:322 particular 313:322 particular 313:322 In particular, microglial activation and communication between microglia, astrocytes, and neurons are hallmarks of the pathogenesis of several neurodegenerative diseases. 24495382 7 93 theme MS-based 1393:1400 arg1 analysis 1402:1409 MS-based analysis 1393:1409 MS-based analysis in normal conditions of microglia for the first time 1393:1462 Especially, a total of 114 CD antigens are identified via MS-based analysis in normal conditions of microglia for the first time. 24495382 11 94 theme membrane 2023:2030 arg1 proteome 2032:2039 membrane proteome 2023:2039 membrane proteome 2023:2039 Collectively, our proteomics and bioinformatics analysis significantly expands the knowledge of the membrane proteome and N-glycoproteome expressed in microglia within the brain and constitutes a foundation for ongoing proteomic studies and drug development for various neurological diseases. 24495382 9 95 theme sites 1768:1772 arg1 identification 1713:1726 improved identification 1704:1726 improved identification of membrane protein and N-glycosylation sites 1704:1772 CONCLUSIONS: Herein, we introduce a novel integrated proteomic approach for improved identification of membrane protein and N-glycosylation sites. 24495382 11 96 theme various 2185:2191 arg1 diseases 2206:2213 various neurological diseases 2185:2213 various neurological diseases 2185:2213 Collectively, our proteomics and bioinformatics analysis significantly expands the knowledge of the membrane proteome and N-glycoproteome expressed in microglia within the brain and constitutes a foundation for ongoing proteomic studies and drug development for various neurological diseases. 24495382 4 97 theme membrane 694:701 arg1 proteins 703:710 membrane proteins 694:710 membrane proteins 694:710 Although membrane proteins and N-glycosylation represent a valuable source of drug target and biomarker discovery, the knowledge of their expressed proteome in microglia is very limited. 24495382 8 98 theme microglial 1542:1551 arg1 function 1553:1560 microglial function 1542:1560 microglial function 1542:1560 Our bioinformatics analysis provides a rich proteomic resource for examining microglial function in, for example, cell-to-cell communication and immune responses. 24495382 3 99 theme microglial 545:554 arg1 activation 556:565 this microglial activation 540:565 this microglial activation 540:565 Membrane proteins and their N-linked glycosylation mediate this microglial activation and regulate many biological process including signal transduction, cell-cell communication, and the immune response. 24495382 4 100 from knowledge 804:812 arg1 microglia 845:853 microglia 845:853 microglia 845:853 Although membrane proteins and N-glycosylation represent a valuable source of drug target and biomarker discovery, the knowledge of their expressed proteome in microglia is very limited. 24495382 1 101 theme cellular 235:242 arg1 mediators 244:252 important cellular mediators 225:252 important cellular mediators of the immune response and neuroinflammatory processes 225:307 BACKGROUND: Microglial cells are resident macrophages of the central nervous system and important cellular mediators of the immune response and neuroinflammatory processes. 24495382 1 101 theme cellular 235:242 arg1 BACKGROUND 137:146 BACKGROUND 137:146 BACKGROUND: Microglial cells are resident macrophages of the central nervous system and important cellular mediators of the immune response and neuroinflammatory processes. 137:308 BACKGROUND: Microglial cells are resident macrophages of the central nervous system and important cellular mediators of the immune response and neuroinflammatory processes. 24495382 7 102 theme antigens 1365:1372 arg1 total 1349:1353 a total 1347:1353 a total of 114 CD antigens 1347:1372 Especially, a total of 114 CD antigens are identified via MS-based analysis in normal conditions of microglia for the first time. 24495382 7 103 theme first 1453:1457 arg1 time 1459:1462 the first time 1449:1462 the first time 1449:1462 Especially, a total of 114 CD antigens are identified via MS-based analysis in normal conditions of microglia for the first time. 24495382 9 104 gly N-glycosylation 1752:1766 arg2 sites 1768:1772 N-glycosylation sites 1752:1772 N-glycosylation sites 1752:1772 CONCLUSIONS: Herein, we introduce a novel integrated proteomic approach for improved identification of membrane protein and N-glycosylation sites. 24495382 1 105 theme immune 261:266 arg1 response 268:275 the immune response 257:275 the immune response 257:275 BACKGROUND: Microglial cells are resident macrophages of the central nervous system and important cellular mediators of the immune response and neuroinflammatory processes. 29249667 0 0 theme Phosphorylation 82:96 arg1 Inhibition 63:72 Inhibition 63:72 Inhibition of PKCζ Phosphorylation in Mouse Embryonic Stem Cells 63:126 O-GlcNAc on PKCζ Inhibits the FGF4-PKCζ-MEK-ERK1/2 Pathway via Inhibition of PKCζ Phosphorylation in Mouse Embryonic Stem Cells. 29249667 6 1 theme PKCζ 981:984 arg1 PKCζ 981:984 PKCζ 981:984 PKCζ 981:984 Here, we showed that the O-GlcNAc on the phosphorylation site of PKCζ inhibits PKCζ phosphorylation (activation) and, consequently, the FGF4-PKCζ-MEK-ERK1/2 pathway in ESCs. 29249667 6 1 theme PKCζ 981:984 arg1 site 973:976 the phosphorylation site 953:976 the phosphorylation site of PKCζ 953:984 Here, we showed that the O-GlcNAc on the phosphorylation site of PKCζ inhibits PKCζ phosphorylation (activation) and, consequently, the FGF4-PKCζ-MEK-ERK1/2 pathway in ESCs. 29249667 5 2 theme proteins 906:913 arg1 threonine 861:869 threonine 861:869 threonine 861:869 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a post-translational modification characterized by the attachment of a single N-acetylglucosamine (GlcNAc) to the serine and threonine residues of nuclear or cytoplasmic proteins. 29249667 5 2 theme proteins 906:913 arg1 serine 850:855 serine 850:855 serine 850:855 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a post-translational modification characterized by the attachment of a single N-acetylglucosamine (GlcNAc) to the serine and threonine residues of nuclear or cytoplasmic proteins. 29249667 4 3 from mechanism 609:617 arg1 ESCs 653:656 ESCs 653:656 ESCs 653:656 However, the inhibitory mechanism of the FGF4-MEK-ERK1/2 pathway in ESCs is uncharacterized. 29249667 0 4 theme PKCζ 77:80 arg1 Phosphorylation 82:96 PKCζ Phosphorylation 77:96 PKCζ Phosphorylation 77:96 O-GlcNAc on PKCζ Inhibits the FGF4-PKCζ-MEK-ERK1/2 Pathway via Inhibition of PKCζ Phosphorylation in Mouse Embryonic Stem Cells. 29249667 5 5 dep serine 850:855 arg1 residues 871:878 residues 871:878 residues 871:878 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a post-translational modification characterized by the attachment of a single N-acetylglucosamine (GlcNAc) to the serine and threonine residues of nuclear or cytoplasmic proteins. 29249667 5 5 dep serine 850:855 arg1 the 846:848 the 846:848 the 846:848 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a post-translational modification characterized by the attachment of a single N-acetylglucosamine (GlcNAc) to the serine and threonine residues of nuclear or cytoplasmic proteins. 29249667 6 6 theme FGF4-PKCζ-MEK-ERK1/2 1052:1071 arg1 pathway 1073:1079 the FGF4-PKCζ-MEK-ERK1/2 pathway 1048:1079 the FGF4-PKCζ-MEK-ERK1/2 pathway in ESCs 1048:1087 Here, we showed that the O-GlcNAc on the phosphorylation site of PKCζ inhibits PKCζ phosphorylation (activation) and, consequently, the FGF4-PKCζ-MEK-ERK1/2 pathway in ESCs. 29249667 0 7 theme Mouse 101:105 arg1 Cells 122:126 Mouse Embryonic Stem Cells 101:126 Mouse Embryonic Stem Cells 101:126 O-GlcNAc on PKCζ Inhibits the FGF4-PKCζ-MEK-ERK1/2 Pathway via Inhibition of PKCζ Phosphorylation in Mouse Embryonic Stem Cells. 29249667 0 8 from O-GlcNAc 0:7 arg1 PKCζ 12:15 PKCζ 12:15 PKCζ 12:15 O-GlcNAc on PKCζ Inhibits the FGF4-PKCζ-MEK-ERK1/2 Pathway via Inhibition of PKCζ Phosphorylation in Mouse Embryonic Stem Cells. 29249667 7 9 theme ESCs 1181:1184 arg1 state 1172:1176 the undifferentiated state 1151:1176 the undifferentiated state of ESCs 1151:1184 Our results demonstrate the mechanism for the maintenance of the undifferentiated state of ESCs via the inhibition of the FGF4-PKCζ-MEK-ERK1/2 pathway by O-GlcNAcylation on PKCζ. 29249667 4 10 theme FGF4-MEK-ERK1/2 626:640 arg1 pathway 642:648 the FGF4-MEK-ERK1/2 pathway 622:648 the FGF4-MEK-ERK1/2 pathway 622:648 However, the inhibitory mechanism of the FGF4-MEK-ERK1/2 pathway in ESCs is uncharacterized. 29249667 5 11 theme single 807:812 arg1 N-acetylglucosamine 814:832 a single N-acetylglucosamine 805:832 a single N-acetylglucosamine (GlcNAc) 805:841 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a post-translational modification characterized by the attachment of a single N-acetylglucosamine (GlcNAc) to the serine and threonine residues of nuclear or cytoplasmic proteins. 29249667 5 11 theme single 807:812 arg1 GlcNAc 835:840 GlcNAc 835:840 GlcNAc 835:840 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a post-translational modification characterized by the attachment of a single N-acetylglucosamine (GlcNAc) to the serine and threonine residues of nuclear or cytoplasmic proteins. 29249667 6 12 theme phosphorylation 957:971 arg1 PKCζ 981:984 PKCζ 981:984 PKCζ 981:984 Here, we showed that the O-GlcNAc on the phosphorylation site of PKCζ inhibits PKCζ phosphorylation (activation) and, consequently, the FGF4-PKCζ-MEK-ERK1/2 pathway in ESCs. 29249667 6 12 theme phosphorylation 957:971 arg1 site 973:976 the phosphorylation site 953:976 the phosphorylation site of PKCζ 953:984 Here, we showed that the O-GlcNAc on the phosphorylation site of PKCζ inhibits PKCζ phosphorylation (activation) and, consequently, the FGF4-PKCζ-MEK-ERK1/2 pathway in ESCs. 29249667 0 13 theme Stem 117:120 arg1 Cells 122:126 Mouse Embryonic Stem Cells 101:126 Mouse Embryonic Stem Cells 101:126 O-GlcNAc on PKCζ Inhibits the FGF4-PKCζ-MEK-ERK1/2 Pathway via Inhibition of PKCζ Phosphorylation in Mouse Embryonic Stem Cells. 29249667 7 14 theme state 1172:1176 arg1 maintenance 1136:1146 the maintenance 1132:1146 the maintenance of the undifferentiated state of ESCs 1132:1184 Our results demonstrate the mechanism for the maintenance of the undifferentiated state of ESCs via the inhibition of the FGF4-PKCζ-MEK-ERK1/2 pathway by O-GlcNAcylation on PKCζ. 29249667 5 15 link O-linked 678:685 arg1 modification 757:768 a post-translational modification 736:768 a post-translational modification characterized by the attachment of a single N-acetylglucosamine (GlcNAc) to the serine and threonine residues of nuclear or cytoplasmic proteins 736:913 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a post-translational modification characterized by the attachment of a single N-acetylglucosamine (GlcNAc) to the serine and threonine residues of nuclear or cytoplasmic proteins. 29249667 5 15 link O-linked 678:685 arg1 O-GlcNAcylation 716:730 O-GlcNAcylation 716:730 O-GlcNAcylation 716:730 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a post-translational modification characterized by the attachment of a single N-acetylglucosamine (GlcNAc) to the serine and threonine residues of nuclear or cytoplasmic proteins. 29249667 5 15 link O-linked 678:685 arg1 β-N-acetylglucosaminylation 687:713 O-linked β-N-acetylglucosaminylation 678:713 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) 678:731 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a post-translational modification characterized by the attachment of a single N-acetylglucosamine (GlcNAc) to the serine and threonine residues of nuclear or cytoplasmic proteins. 29249667 0 16 theme Embryonic 107:115 arg1 Cells 122:126 Mouse Embryonic Stem Cells 101:126 Mouse Embryonic Stem Cells 101:126 O-GlcNAc on PKCζ Inhibits the FGF4-PKCζ-MEK-ERK1/2 Pathway via Inhibition of PKCζ Phosphorylation in Mouse Embryonic Stem Cells. 29249667 7 17 theme FGF4-PKCζ-MEK-ERK1/2 1212:1231 arg1 pathway 1233:1239 the FGF4-PKCζ-MEK-ERK1/2 pathway 1208:1239 the FGF4-PKCζ-MEK-ERK1/2 pathway 1208:1239 Our results demonstrate the mechanism for the maintenance of the undifferentiated state of ESCs via the inhibition of the FGF4-PKCζ-MEK-ERK1/2 pathway by O-GlcNAcylation on PKCζ. 29249667 3 18 theme undifferentiated 561:576 arg1 state 578:582 the undifferentiated state 557:582 the undifferentiated state 557:582 The FGF4-MEK-ERK1/2 pathway is inhibited to maintain ESCs in the undifferentiated state. 29249667 5 19 theme N-acetylglucosamine 814:832 arg1 attachment 791:800 the attachment 787:800 the attachment of a single N-acetylglucosamine (GlcNAc) to the serine and threonine residues of nuclear or cytoplasmic proteins 787:913 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a post-translational modification characterized by the attachment of a single N-acetylglucosamine (GlcNAc) to the serine and threonine residues of nuclear or cytoplasmic proteins. 29249667 5 20 theme O-linked 678:685 arg1 modification 757:768 a post-translational modification 736:768 a post-translational modification characterized by the attachment of a single N-acetylglucosamine (GlcNAc) to the serine and threonine residues of nuclear or cytoplasmic proteins 736:913 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a post-translational modification characterized by the attachment of a single N-acetylglucosamine (GlcNAc) to the serine and threonine residues of nuclear or cytoplasmic proteins. 29249667 5 20 theme O-linked 678:685 arg1 O-GlcNAcylation 716:730 O-GlcNAcylation 716:730 O-GlcNAcylation 716:730 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a post-translational modification characterized by the attachment of a single N-acetylglucosamine (GlcNAc) to the serine and threonine residues of nuclear or cytoplasmic proteins. 29249667 5 20 theme O-linked 678:685 arg1 β-N-acetylglucosaminylation 687:713 O-linked β-N-acetylglucosaminylation 678:713 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) 678:731 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a post-translational modification characterized by the attachment of a single N-acetylglucosamine (GlcNAc) to the serine and threonine residues of nuclear or cytoplasmic proteins. 29249667 5 21 attach attachment 791:800 arg1 threonine 861:869 threonine 861:869 threonine 861:869 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a post-translational modification characterized by the attachment of a single N-acetylglucosamine (GlcNAc) to the serine and threonine residues of nuclear or cytoplasmic proteins. 29249667 5 21 attach attachment 791:800 arg1 serine 850:855 serine 850:855 serine 850:855 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a post-translational modification characterized by the attachment of a single N-acetylglucosamine (GlcNAc) to the serine and threonine residues of nuclear or cytoplasmic proteins. 29249667 5 21 attach attachment 791:800 arg2 GlcNAc 835:840 GlcNAc 835:840 GlcNAc 835:840 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a post-translational modification characterized by the attachment of a single N-acetylglucosamine (GlcNAc) to the serine and threonine residues of nuclear or cytoplasmic proteins. 29249667 5 21 attach attachment 791:800 arg2 N-acetylglucosamine 814:832 a single N-acetylglucosamine 805:832 a single N-acetylglucosamine (GlcNAc) 805:841 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a post-translational modification characterized by the attachment of a single N-acetylglucosamine (GlcNAc) to the serine and threonine residues of nuclear or cytoplasmic proteins. 29249667 2 22 theme signal-related 414:427 arg1 kinase 429:434 mitogen-activated protein kinase/extracellular signal-related kinase 367:434 mitogen-activated protein kinase/extracellular signal-related kinase (MEK) 367:440 Fibroblast growth factor 4 (FGF4) signaling induces differentiation from ESCs via the phosphorylation of downstream molecules such as mitogen-activated protein kinase/extracellular signal-related kinase (MEK) and extracellular signal-related kinase 1/2 (ERK1/2). 29249667 2 22 theme signal-related 414:427 arg1 MEK 437:439 MEK 437:439 MEK 437:439 Fibroblast growth factor 4 (FGF4) signaling induces differentiation from ESCs via the phosphorylation of downstream molecules such as mitogen-activated protein kinase/extracellular signal-related kinase (MEK) and extracellular signal-related kinase 1/2 (ERK1/2). 29249667 5 23 theme nuclear 883:889 arg1 proteins 906:913 nuclear or cytoplasmic proteins 883:913 nuclear or cytoplasmic proteins 883:913 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a post-translational modification characterized by the attachment of a single N-acetylglucosamine (GlcNAc) to the serine and threonine residues of nuclear or cytoplasmic proteins. 29249667 7 24 theme undifferentiated 1155:1170 arg1 state 1172:1176 the undifferentiated state 1151:1176 the undifferentiated state of ESCs 1151:1184 Our results demonstrate the mechanism for the maintenance of the undifferentiated state of ESCs via the inhibition of the FGF4-PKCζ-MEK-ERK1/2 pathway by O-GlcNAcylation on PKCζ. 29249667 1 25 theme multiple 182:189 arg1 types 196:200 multiple cell types 182:200 multiple cell types 182:200 Mouse embryonic stem cells (ESCs) differentiate into multiple cell types during organismal development. 29249667 1 26 theme cell 191:194 arg1 types 196:200 multiple cell types 182:200 multiple cell types 182:200 Mouse embryonic stem cells (ESCs) differentiate into multiple cell types during organismal development. 29249667 2 27 theme signal-related 460:473 arg1 kinase 475:480 extracellular signal-related kinase 1/2 446:484 extracellular signal-related kinase 1/2 (ERK1/2) 446:493 Fibroblast growth factor 4 (FGF4) signaling induces differentiation from ESCs via the phosphorylation of downstream molecules such as mitogen-activated protein kinase/extracellular signal-related kinase (MEK) and extracellular signal-related kinase 1/2 (ERK1/2). 29249667 2 27 theme signal-related 460:473 arg1 ERK1/2 487:492 ERK1/2 487:492 ERK1/2 487:492 Fibroblast growth factor 4 (FGF4) signaling induces differentiation from ESCs via the phosphorylation of downstream molecules such as mitogen-activated protein kinase/extracellular signal-related kinase (MEK) and extracellular signal-related kinase 1/2 (ERK1/2). 29249667 4 28 theme inhibitory 598:607 arg1 mechanism 609:617 the inhibitory mechanism 594:617 the inhibitory mechanism of the FGF4-MEK-ERK1/2 pathway in ESCs 594:656 However, the inhibitory mechanism of the FGF4-MEK-ERK1/2 pathway in ESCs is uncharacterized. 29249667 4 28 theme inhibitory 598:607 arg1 uncharacterized 661:675 uncharacterized 661:675 uncharacterized 661:675 However, the inhibitory mechanism of the FGF4-MEK-ERK1/2 pathway in ESCs is uncharacterized. 29249667 6 29 from pathway 1073:1079 arg1 ESCs 1084:1087 ESCs 1084:1087 ESCs 1084:1087 Here, we showed that the O-GlcNAc on the phosphorylation site of PKCζ inhibits PKCζ phosphorylation (activation) and, consequently, the FGF4-PKCζ-MEK-ERK1/2 pathway in ESCs. 29249667 1 30 theme stem 145:148 arg1 cells 150:154 Mouse embryonic stem cells 129:154 Mouse embryonic stem cells (ESCs) 129:161 Mouse embryonic stem cells (ESCs) differentiate into multiple cell types during organismal development. 29249667 1 30 theme stem 145:148 arg1 ESCs 157:160 ESCs 157:160 ESCs 157:160 Mouse embryonic stem cells (ESCs) differentiate into multiple cell types during organismal development. 29249667 0 31 theme FGF4-PKCζ-MEK-ERK1/2 30:49 arg1 Pathway 51:57 the FGF4-PKCζ-MEK-ERK1/2 Pathway 26:57 the FGF4-PKCζ-MEK-ERK1/2 Pathway 26:57 O-GlcNAc on PKCζ Inhibits the FGF4-PKCζ-MEK-ERK1/2 Pathway via Inhibition of PKCζ Phosphorylation in Mouse Embryonic Stem Cells. 29249667 2 32 theme growth 244:249 arg1 factor 251:256 Fibroblast growth factor 4 233:258 Fibroblast growth factor 4 (FGF4) signaling 233:275 Fibroblast growth factor 4 (FGF4) signaling induces differentiation from ESCs via the phosphorylation of downstream molecules such as mitogen-activated protein kinase/extracellular signal-related kinase (MEK) and extracellular signal-related kinase 1/2 (ERK1/2). 29249667 2 32 theme growth 244:249 arg1 FGF4 261:264 FGF4 261:264 FGF4 261:264 Fibroblast growth factor 4 (FGF4) signaling induces differentiation from ESCs via the phosphorylation of downstream molecules such as mitogen-activated protein kinase/extracellular signal-related kinase (MEK) and extracellular signal-related kinase 1/2 (ERK1/2). 29249667 2 33 theme kinase/extracellular 393:412 arg1 kinase 429:434 mitogen-activated protein kinase/extracellular signal-related kinase 367:434 mitogen-activated protein kinase/extracellular signal-related kinase (MEK) 367:440 Fibroblast growth factor 4 (FGF4) signaling induces differentiation from ESCs via the phosphorylation of downstream molecules such as mitogen-activated protein kinase/extracellular signal-related kinase (MEK) and extracellular signal-related kinase 1/2 (ERK1/2). 29249667 2 33 theme kinase/extracellular 393:412 arg1 MEK 437:439 MEK 437:439 MEK 437:439 Fibroblast growth factor 4 (FGF4) signaling induces differentiation from ESCs via the phosphorylation of downstream molecules such as mitogen-activated protein kinase/extracellular signal-related kinase (MEK) and extracellular signal-related kinase 1/2 (ERK1/2). 29249667 7 34 theme pathway 1233:1239 arg1 inhibition 1194:1203 the inhibition 1190:1203 the inhibition of the FGF4-PKCζ-MEK-ERK1/2 pathway by O-GlcNAcylation on PKCζ 1190:1266 Our results demonstrate the mechanism for the maintenance of the undifferentiated state of ESCs via the inhibition of the FGF4-PKCζ-MEK-ERK1/2 pathway by O-GlcNAcylation on PKCζ. 29249667 2 35 theme Fibroblast 233:242 arg1 factor 251:256 Fibroblast growth factor 4 233:258 Fibroblast growth factor 4 (FGF4) signaling 233:275 Fibroblast growth factor 4 (FGF4) signaling induces differentiation from ESCs via the phosphorylation of downstream molecules such as mitogen-activated protein kinase/extracellular signal-related kinase (MEK) and extracellular signal-related kinase 1/2 (ERK1/2). 29249667 2 35 theme Fibroblast 233:242 arg1 FGF4 261:264 FGF4 261:264 FGF4 261:264 Fibroblast growth factor 4 (FGF4) signaling induces differentiation from ESCs via the phosphorylation of downstream molecules such as mitogen-activated protein kinase/extracellular signal-related kinase (MEK) and extracellular signal-related kinase 1/2 (ERK1/2). 29249667 1 36 theme organismal 209:218 arg1 development 220:230 organismal development 209:230 organismal development 209:230 Mouse embryonic stem cells (ESCs) differentiate into multiple cell types during organismal development. 29249667 6 37 from phosphorylation 1000:1014 arg1 ESCs 1084:1087 ESCs 1084:1087 ESCs 1084:1087 Here, we showed that the O-GlcNAc on the phosphorylation site of PKCζ inhibits PKCζ phosphorylation (activation) and, consequently, the FGF4-PKCζ-MEK-ERK1/2 pathway in ESCs. 29249667 0 38 from Inhibition 63:72 arg1 Cells 122:126 Mouse Embryonic Stem Cells 101:126 Mouse Embryonic Stem Cells 101:126 O-GlcNAc on PKCζ Inhibits the FGF4-PKCζ-MEK-ERK1/2 Pathway via Inhibition of PKCζ Phosphorylation in Mouse Embryonic Stem Cells. 29249667 7 39 from inhibition 1194:1203 arg1 PKCζ 1263:1266 PKCζ 1263:1266 PKCζ 1263:1266 Our results demonstrate the mechanism for the maintenance of the undifferentiated state of ESCs via the inhibition of the FGF4-PKCζ-MEK-ERK1/2 pathway by O-GlcNAcylation on PKCζ. 29249667 2 40 theme molecules 349:357 arg1 phosphorylation 319:333 the phosphorylation 315:333 the phosphorylation of downstream molecules such as mitogen-activated protein kinase/extracellular signal-related kinase (MEK) and extracellular signal-related kinase 1/2 (ERK1/2) 315:493 Fibroblast growth factor 4 (FGF4) signaling induces differentiation from ESCs via the phosphorylation of downstream molecules such as mitogen-activated protein kinase/extracellular signal-related kinase (MEK) and extracellular signal-related kinase 1/2 (ERK1/2). 29249667 4 41 theme pathway 642:648 arg1 mechanism 609:617 the inhibitory mechanism 594:617 the inhibitory mechanism of the FGF4-MEK-ERK1/2 pathway in ESCs 594:656 However, the inhibitory mechanism of the FGF4-MEK-ERK1/2 pathway in ESCs is uncharacterized. 29249667 4 41 theme pathway 642:648 arg1 uncharacterized 661:675 uncharacterized 661:675 uncharacterized 661:675 However, the inhibitory mechanism of the FGF4-MEK-ERK1/2 pathway in ESCs is uncharacterized. 29249667 5 42 theme post-translational 738:755 arg1 modification 757:768 a post-translational modification 736:768 a post-translational modification characterized by the attachment of a single N-acetylglucosamine (GlcNAc) to the serine and threonine residues of nuclear or cytoplasmic proteins 736:913 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a post-translational modification characterized by the attachment of a single N-acetylglucosamine (GlcNAc) to the serine and threonine residues of nuclear or cytoplasmic proteins. 29249667 5 42 theme post-translational 738:755 arg1 β-N-acetylglucosaminylation 687:713 O-linked β-N-acetylglucosaminylation 678:713 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) 678:731 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a post-translational modification characterized by the attachment of a single N-acetylglucosamine (GlcNAc) to the serine and threonine residues of nuclear or cytoplasmic proteins. 29249667 2 43 theme downstream 338:347 arg1 kinase 429:434 mitogen-activated protein kinase/extracellular signal-related kinase 367:434 mitogen-activated protein kinase/extracellular signal-related kinase (MEK) 367:440 Fibroblast growth factor 4 (FGF4) signaling induces differentiation from ESCs via the phosphorylation of downstream molecules such as mitogen-activated protein kinase/extracellular signal-related kinase (MEK) and extracellular signal-related kinase 1/2 (ERK1/2). 29249667 2 43 theme downstream 338:347 arg1 molecules 349:357 downstream molecules 338:357 downstream molecules such as mitogen-activated protein kinase/extracellular signal-related kinase (MEK) and extracellular signal-related kinase 1/2 (ERK1/2) 338:493 Fibroblast growth factor 4 (FGF4) signaling induces differentiation from ESCs via the phosphorylation of downstream molecules such as mitogen-activated protein kinase/extracellular signal-related kinase (MEK) and extracellular signal-related kinase 1/2 (ERK1/2). 29249667 2 43 theme downstream 338:347 arg1 kinase 475:480 extracellular signal-related kinase 1/2 446:484 extracellular signal-related kinase 1/2 (ERK1/2) 446:493 Fibroblast growth factor 4 (FGF4) signaling induces differentiation from ESCs via the phosphorylation of downstream molecules such as mitogen-activated protein kinase/extracellular signal-related kinase (MEK) and extracellular signal-related kinase 1/2 (ERK1/2). 29249667 6 44 theme PKCζ 995:998 arg1 activation 1017:1026 activation 1017:1026 activation 1017:1026 Here, we showed that the O-GlcNAc on the phosphorylation site of PKCζ inhibits PKCζ phosphorylation (activation) and, consequently, the FGF4-PKCζ-MEK-ERK1/2 pathway in ESCs. 29249667 6 44 theme PKCζ 995:998 arg1 phosphorylation 1000:1014 PKCζ phosphorylation 995:1014 PKCζ phosphorylation (activation) 995:1027 Here, we showed that the O-GlcNAc on the phosphorylation site of PKCζ inhibits PKCζ phosphorylation (activation) and, consequently, the FGF4-PKCζ-MEK-ERK1/2 pathway in ESCs. 29249667 1 45 theme Mouse 129:133 arg1 cells 150:154 Mouse embryonic stem cells 129:154 Mouse embryonic stem cells (ESCs) 129:161 Mouse embryonic stem cells (ESCs) differentiate into multiple cell types during organismal development. 29249667 1 45 theme Mouse 129:133 arg1 ESCs 157:160 ESCs 157:160 ESCs 157:160 Mouse embryonic stem cells (ESCs) differentiate into multiple cell types during organismal development. 29249667 5 46 theme cytoplasmic 894:904 arg1 proteins 906:913 nuclear or cytoplasmic proteins 883:913 nuclear or cytoplasmic proteins 883:913 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a post-translational modification characterized by the attachment of a single N-acetylglucosamine (GlcNAc) to the serine and threonine residues of nuclear or cytoplasmic proteins. 29249667 1 47 theme embryonic 135:143 arg1 cells 150:154 Mouse embryonic stem cells 129:154 Mouse embryonic stem cells (ESCs) 129:161 Mouse embryonic stem cells (ESCs) differentiate into multiple cell types during organismal development. 29249667 1 47 theme embryonic 135:143 arg1 ESCs 157:160 ESCs 157:160 ESCs 157:160 Mouse embryonic stem cells (ESCs) differentiate into multiple cell types during organismal development. 29249667 3 48 theme FGF4-MEK-ERK1/2 500:514 arg1 pathway 516:522 The FGF4-MEK-ERK1/2 pathway 496:522 The FGF4-MEK-ERK1/2 pathway 496:522 The FGF4-MEK-ERK1/2 pathway is inhibited to maintain ESCs in the undifferentiated state. 29249667 2 49 theme extracellular 446:458 arg1 kinase 475:480 extracellular signal-related kinase 1/2 446:484 extracellular signal-related kinase 1/2 (ERK1/2) 446:493 Fibroblast growth factor 4 (FGF4) signaling induces differentiation from ESCs via the phosphorylation of downstream molecules such as mitogen-activated protein kinase/extracellular signal-related kinase (MEK) and extracellular signal-related kinase 1/2 (ERK1/2). 29249667 2 49 theme extracellular 446:458 arg1 ERK1/2 487:492 ERK1/2 487:492 ERK1/2 487:492 Fibroblast growth factor 4 (FGF4) signaling induces differentiation from ESCs via the phosphorylation of downstream molecules such as mitogen-activated protein kinase/extracellular signal-related kinase (MEK) and extracellular signal-related kinase 1/2 (ERK1/2). 29249667 2 50 theme protein 385:391 arg1 kinase 429:434 mitogen-activated protein kinase/extracellular signal-related kinase 367:434 mitogen-activated protein kinase/extracellular signal-related kinase (MEK) 367:440 Fibroblast growth factor 4 (FGF4) signaling induces differentiation from ESCs via the phosphorylation of downstream molecules such as mitogen-activated protein kinase/extracellular signal-related kinase (MEK) and extracellular signal-related kinase 1/2 (ERK1/2). 29249667 2 50 theme protein 385:391 arg1 MEK 437:439 MEK 437:439 MEK 437:439 Fibroblast growth factor 4 (FGF4) signaling induces differentiation from ESCs via the phosphorylation of downstream molecules such as mitogen-activated protein kinase/extracellular signal-related kinase (MEK) and extracellular signal-related kinase 1/2 (ERK1/2). 29249667 2 51 theme factor 251:256 arg1 signaling 267:275 Fibroblast growth factor 4 (FGF4) signaling 233:275 Fibroblast growth factor 4 (FGF4) signaling 233:275 Fibroblast growth factor 4 (FGF4) signaling induces differentiation from ESCs via the phosphorylation of downstream molecules such as mitogen-activated protein kinase/extracellular signal-related kinase (MEK) and extracellular signal-related kinase 1/2 (ERK1/2). 29249667 2 52 theme mitogen-activated 367:383 arg1 kinase 429:434 mitogen-activated protein kinase/extracellular signal-related kinase 367:434 mitogen-activated protein kinase/extracellular signal-related kinase (MEK) 367:440 Fibroblast growth factor 4 (FGF4) signaling induces differentiation from ESCs via the phosphorylation of downstream molecules such as mitogen-activated protein kinase/extracellular signal-related kinase (MEK) and extracellular signal-related kinase 1/2 (ERK1/2). 29249667 2 52 theme mitogen-activated 367:383 arg1 MEK 437:439 MEK 437:439 MEK 437:439 Fibroblast growth factor 4 (FGF4) signaling induces differentiation from ESCs via the phosphorylation of downstream molecules such as mitogen-activated protein kinase/extracellular signal-related kinase (MEK) and extracellular signal-related kinase 1/2 (ERK1/2). 29249667 2 53 from ESCs 306:309 arg1 differentiation 285:299 differentiation 285:299 differentiation from ESCs 285:309 Fibroblast growth factor 4 (FGF4) signaling induces differentiation from ESCs via the phosphorylation of downstream molecules such as mitogen-activated protein kinase/extracellular signal-related kinase (MEK) and extracellular signal-related kinase 1/2 (ERK1/2). 29249667 6 54 from O-GlcNAc 941:948 arg1 PKCζ 981:984 PKCζ 981:984 PKCζ 981:984 Here, we showed that the O-GlcNAc on the phosphorylation site of PKCζ inhibits PKCζ phosphorylation (activation) and, consequently, the FGF4-PKCζ-MEK-ERK1/2 pathway in ESCs. 29249667 6 54 from O-GlcNAc 941:948 arg1 site 973:976 the phosphorylation site 953:976 the phosphorylation site of PKCζ 953:984 Here, we showed that the O-GlcNAc on the phosphorylation site of PKCζ inhibits PKCζ phosphorylation (activation) and, consequently, the FGF4-PKCζ-MEK-ERK1/2 pathway in ESCs. 28694069 1 0 from 297 280:282 arg1 presence 217:224 the presence 213:224 the presence of a single N-linked glycosylation site at asparagine 297 of the Fc 213:292 The binding of human IgG1 to human Fc gamma receptors (hFcγRs) is highly sensitive to the presence of a single N-linked glycosylation site at asparagine 297 of the Fc, with deglycosylation resulting in a complete loss of hFcγR binding. 28694069 1 0 from 297 280:282 arg1 site 261:264 a single N-linked glycosylation site 229:264 a single N-linked glycosylation site at asparagine 297 of the Fc 229:292 The binding of human IgG1 to human Fc gamma receptors (hFcγRs) is highly sensitive to the presence of a single N-linked glycosylation site at asparagine 297 of the Fc, with deglycosylation resulting in a complete loss of hFcγR binding. 28694069 3 1 theme aglycosylated 639:651 arg1 variants 657:664 aglycosylated IgG variants 639:664 aglycosylated IgG variants 639:664 In the present study, we demonstrate that aglycosylated IgG variants can be engineered to productively engage with FcγRIIIA, as well as the human Fc gamma RII subset. 28694069 6 2 theme main 1098:1101 arg1 dimers 1082:1087 hFcγRI and hFcγRIIIA dimers 1061:1087 hFcγRI and hFcγRIIIA dimers 1061:1087 A mathematical model of phagocytosis suggests that hFcγRI and hFcγRIIIA dimers were the main drivers of phagocytosis. 28694069 6 2 theme main 1098:1101 arg1 drivers 1103:1109 the main drivers 1094:1109 the main drivers of phagocytosis 1094:1125 A mathematical model of phagocytosis suggests that hFcγRI and hFcγRIIIA dimers were the main drivers of phagocytosis. 28694069 1 3 theme Fc 162:163 arg1 receptors 171:179 human Fc gamma receptors 156:179 human Fc gamma receptors (hFcγRs) 156:188 The binding of human IgG1 to human Fc gamma receptors (hFcγRs) is highly sensitive to the presence of a single N-linked glycosylation site at asparagine 297 of the Fc, with deglycosylation resulting in a complete loss of hFcγR binding. 28694069 1 3 theme Fc 162:163 arg1 hFcγRs 182:187 hFcγRs 182:187 hFcγRs 182:187 The binding of human IgG1 to human Fc gamma receptors (hFcγRs) is highly sensitive to the presence of a single N-linked glycosylation site at asparagine 297 of the Fc, with deglycosylation resulting in a complete loss of hFcγR binding. 28694069 4 4 theme aglycosylated 833:845 arg1 variants 851:858 the aglycosylated IgG variants 829:858 the aglycosylated IgG variants 829:858 We also assess the biophysical properties and serum half-life of the aglycosylated IgG variants to measure stability. 28694069 0 5 theme Fc 110:111 arg1 RIIIAs 119:124 Fc Gamma RIIIAs 110:124 Fc Gamma RIIIAs 110:124 Engineering Aglycosylated IgG Variants with Wild-Type or Improved Binding Affinity to Human Fc Gamma RIIA and Fc Gamma RIIIAs. 28694069 4 6 gly aglycosylated 833:845 arg1 variants 851:858 the aglycosylated IgG variants 829:858 the aglycosylated IgG variants 829:858 We also assess the biophysical properties and serum half-life of the aglycosylated IgG variants to measure stability. 28694069 4 7 theme variants 851:858 arg1 half-life 816:824 serum half-life 810:824 serum half-life of the aglycosylated IgG variants to measure stability 810:879 We also assess the biophysical properties and serum half-life of the aglycosylated IgG variants to measure stability. 28694069 4 7 theme variants 851:858 arg1 properties 795:804 the biophysical properties 779:804 the biophysical properties 779:804 We also assess the biophysical properties and serum half-life of the aglycosylated IgG variants to measure stability. 28694069 2 8 link N-linked 514:521 arg1 requirement 563:573 a strict requirement 554:573 a strict requirement for hFcγR engagement 554:594 Previously, we demonstrated that aglycosylated human IgG1 Fc variants can engage the human FcγRII class of the low-affinity hFcγRs, demonstrating that N-linked glycosylation of the Fc is not a strict requirement for hFcγR engagement. 28694069 2 8 link N-linked 514:521 arg1 glycosylation 523:535 N-linked glycosylation 514:535 N-linked glycosylation of the Fc 514:545 Previously, we demonstrated that aglycosylated human IgG1 Fc variants can engage the human FcγRII class of the low-affinity hFcγRs, demonstrating that N-linked glycosylation of the Fc is not a strict requirement for hFcγR engagement. 28694069 4 9 theme serum 810:814 arg1 half-life 816:824 serum half-life 810:824 serum half-life of the aglycosylated IgG variants to measure stability 810:879 We also assess the biophysical properties and serum half-life of the aglycosylated IgG variants to measure stability. 28694069 8 10 theme CH2 1400:1402 arg1 DTT-IYG 1414:1420 DTT-IYG 1414:1420 DTT-IYG 1414:1420 While deuterium incorporation was similar across most of the protein, several peptides within the CH2 domain of DTT-IYG showed differential deuterium uptake in the peptide region of the FG loop as compared to the aglycosylated N297Q. 28694069 8 10 theme CH2 1400:1402 arg1 domain 1404:1409 the CH2 domain 1396:1409 the CH2 domain of DTT-IYG 1396:1420 While deuterium incorporation was similar across most of the protein, several peptides within the CH2 domain of DTT-IYG showed differential deuterium uptake in the peptide region of the FG loop as compared to the aglycosylated N297Q. 28694069 1 11 theme hFcγR 348:352 arg1 binding 354:360 hFcγR binding 348:360 hFcγR binding 348:360 The binding of human IgG1 to human Fc gamma receptors (hFcγRs) is highly sensitive to the presence of a single N-linked glycosylation site at asparagine 297 of the Fc, with deglycosylation resulting in a complete loss of hFcγR binding. 28694069 1 12 gly glycosylation 247:259 arg2 297 280:282 asparagine 297 269:282 asparagine 297 of the Fc 269:292 The binding of human IgG1 to human Fc gamma receptors (hFcγRs) is highly sensitive to the presence of a single N-linked glycosylation site at asparagine 297 of the Fc, with deglycosylation resulting in a complete loss of hFcγR binding. 28694069 1 12 gly glycosylation 247:259 arg2 site 261:264 a single N-linked glycosylation site 229:264 a single N-linked glycosylation site at asparagine 297 of the Fc 229:292 The binding of human IgG1 to human Fc gamma receptors (hFcγRs) is highly sensitive to the presence of a single N-linked glycosylation site at asparagine 297 of the Fc, with deglycosylation resulting in a complete loss of hFcγR binding. 28694069 2 13 gly glycosylation 523:535 arg1 Fc 544:545 the Fc 540:545 the Fc 540:545 Previously, we demonstrated that aglycosylated human IgG1 Fc variants can engage the human FcγRII class of the low-affinity hFcγRs, demonstrating that N-linked glycosylation of the Fc is not a strict requirement for hFcγR engagement. 28694069 5 14 theme tumor 985:989 arg1 phagocytosis 996:1007 tumor cell phagocytosis 985:1007 tumor cell phagocytosis 985:1007 Aglycosylated constructs N297D/S298T (DTT)-K326I/A327Y/L328G (IYG) and N297D/S298A-IYG optimally drove tumor cell phagocytosis. 28694069 10 15 contain have 1675:1678 arg2 potential 1684:1692 the potential to allow therapeutic antibodies to be produced in virtually any expression system 1680:1774 the potential to allow therapeutic antibodies to be produced in virtually any expression system 1680:1774 These aglycosylated variants have the potential to allow therapeutic antibodies to be produced in virtually any expression system and still maintain effector function. 28694069 10 15 contain have 1675:1678 arg1 variants 1666:1673 These aglycosylated variants 1646:1673 These aglycosylated variants 1646:1673 These aglycosylated variants have the potential to allow therapeutic antibodies to be produced in virtually any expression system and still maintain effector function. 28694069 7 16 theme lung 1285:1288 arg1 metastases 1290:1299 lung metastases 1285:1299 lung metastases 1285:1299 In vivo tumor control of B16F10 lung metastases further confirmed the variant DTT-IYG to be the best at restoring wild-type-like properties in prevention of lung metastases. 28694069 7 17 theme metastases 1165:1174 arg1 control 1142:1148 In vivo tumor control 1128:1148 In vivo tumor control of B16F10 lung metastases 1128:1174 In vivo tumor control of B16F10 lung metastases further confirmed the variant DTT-IYG to be the best at restoring wild-type-like properties in prevention of lung metastases. 28694069 10 18 gly aglycosylated 1652:1664 arg1 variants 1666:1673 These aglycosylated variants 1646:1673 These aglycosylated variants 1646:1673 These aglycosylated variants have the potential to allow therapeutic antibodies to be produced in virtually any expression system and still maintain effector function. 28694069 10 19 theme any 1754:1756 arg1 system 1769:1774 virtually any expression system 1744:1774 virtually any expression system 1744:1774 These aglycosylated variants have the potential to allow therapeutic antibodies to be produced in virtually any expression system and still maintain effector function. 28694069 8 20 theme deuterium 1442:1450 arg1 uptake 1452:1457 differential deuterium uptake 1429:1457 differential deuterium uptake in the peptide region of the FG loop 1429:1494 While deuterium incorporation was similar across most of the protein, several peptides within the CH2 domain of DTT-IYG showed differential deuterium uptake in the peptide region of the FG loop as compared to the aglycosylated N297Q. 28694069 3 21 theme gamma 746:750 arg1 RII 752:754 the human Fc gamma RII 733:754 the human Fc gamma RII subset 733:761 In the present study, we demonstrate that aglycosylated IgG variants can be engineered to productively engage with FcγRIIIA, as well as the human Fc gamma RII subset. 28694069 7 22 theme B16F10 1153:1158 arg1 metastases 1165:1174 B16F10 lung metastases 1153:1174 B16F10 lung metastases 1153:1174 In vivo tumor control of B16F10 lung metastases further confirmed the variant DTT-IYG to be the best at restoring wild-type-like properties in prevention of lung metastases. 28694069 1 23 theme Fc 291:292 arg1 297 280:282 asparagine 297 269:282 asparagine 297 of the Fc 269:292 The binding of human IgG1 to human Fc gamma receptors (hFcγRs) is highly sensitive to the presence of a single N-linked glycosylation site at asparagine 297 of the Fc, with deglycosylation resulting in a complete loss of hFcγR binding. 28694069 1 24 theme human 142:146 arg1 IgG1 148:151 human IgG1 142:151 human IgG1 142:151 The binding of human IgG1 to human Fc gamma receptors (hFcγRs) is highly sensitive to the presence of a single N-linked glycosylation site at asparagine 297 of the Fc, with deglycosylation resulting in a complete loss of hFcγR binding. 28694069 3 25 theme human 737:741 arg1 RII 752:754 the human Fc gamma RII 733:754 the human Fc gamma RII subset 733:761 In the present study, we demonstrate that aglycosylated IgG variants can be engineered to productively engage with FcγRIIIA, as well as the human Fc gamma RII subset. 28694069 0 26 theme Fc 92:93 arg1 RIIA 101:104 Human Fc Gamma RIIA 86:104 Human Fc Gamma RIIA 86:104 Engineering Aglycosylated IgG Variants with Wild-Type or Improved Binding Affinity to Human Fc Gamma RIIA and Fc Gamma RIIIAs. 28694069 2 27 theme FcγRII 454:459 arg1 class 461:465 the human FcγRII class 444:465 the human FcγRII class of the low-affinity hFcγRs 444:492 Previously, we demonstrated that aglycosylated human IgG1 Fc variants can engage the human FcγRII class of the low-affinity hFcγRs, demonstrating that N-linked glycosylation of the Fc is not a strict requirement for hFcγR engagement. 28694069 8 28 theme peptide 1466:1472 arg1 region 1474:1479 the peptide region 1462:1479 the peptide region of the FG loop 1462:1494 While deuterium incorporation was similar across most of the protein, several peptides within the CH2 domain of DTT-IYG showed differential deuterium uptake in the peptide region of the FG loop as compared to the aglycosylated N297Q. 28694069 3 29 dep RII 752:754 arg1 subset 756:761 subset 756:761 the human Fc gamma RII subset 733:761 In the present study, we demonstrate that aglycosylated IgG variants can be engineered to productively engage with FcγRIIIA, as well as the human Fc gamma RII subset. 28694069 8 30 theme FG 1488:1489 arg1 loop 1491:1494 the FG loop 1484:1494 the FG loop 1484:1494 While deuterium incorporation was similar across most of the protein, several peptides within the CH2 domain of DTT-IYG showed differential deuterium uptake in the peptide region of the FG loop as compared to the aglycosylated N297Q. 28694069 0 31 theme IgG 26:28 arg1 Variants 30:37 Aglycosylated IgG Variants 12:37 Aglycosylated IgG Variants 12:37 Engineering Aglycosylated IgG Variants with Wild-Type or Improved Binding Affinity to Human Fc Gamma RIIA and Fc Gamma RIIIAs. 28694069 1 32 theme N-linked 238:245 arg1 site 261:264 a single N-linked glycosylation site 229:264 a single N-linked glycosylation site at asparagine 297 of the Fc 229:292 The binding of human IgG1 to human Fc gamma receptors (hFcγRs) is highly sensitive to the presence of a single N-linked glycosylation site at asparagine 297 of the Fc, with deglycosylation resulting in a complete loss of hFcγR binding. 28694069 7 33 theme wild-type-like 1242:1255 arg1 properties 1257:1266 wild-type-like properties 1242:1266 wild-type-like properties 1242:1266 In vivo tumor control of B16F10 lung metastases further confirmed the variant DTT-IYG to be the best at restoring wild-type-like properties in prevention of lung metastases. 28694069 2 34 theme Fc 421:422 arg1 variants 424:431 aglycosylated human IgG1 Fc variants 396:431 aglycosylated human IgG1 Fc variants 396:431 Previously, we demonstrated that aglycosylated human IgG1 Fc variants can engage the human FcγRII class of the low-affinity hFcγRs, demonstrating that N-linked glycosylation of the Fc is not a strict requirement for hFcγR engagement. 28694069 3 35 gly aglycosylated 639:651 arg1 variants 657:664 aglycosylated IgG variants 639:664 aglycosylated IgG variants 639:664 In the present study, we demonstrate that aglycosylated IgG variants can be engineered to productively engage with FcγRIIIA, as well as the human Fc gamma RII subset. 28694069 10 36 theme effector 1795:1802 arg1 function 1804:1811 effector function 1795:1811 effector function 1795:1811 These aglycosylated variants have the potential to allow therapeutic antibodies to be produced in virtually any expression system and still maintain effector function. 28694069 1 37 theme site 261:264 arg1 presence 217:224 the presence 213:224 the presence of a single N-linked glycosylation site at asparagine 297 of the Fc 213:292 The binding of human IgG1 to human Fc gamma receptors (hFcγRs) is highly sensitive to the presence of a single N-linked glycosylation site at asparagine 297 of the Fc, with deglycosylation resulting in a complete loss of hFcγR binding. 28694069 0 38 gly Aglycosylated 12:24 arg1 Variants 30:37 Aglycosylated IgG Variants 12:37 Aglycosylated IgG Variants 12:37 Engineering Aglycosylated IgG Variants with Wild-Type or Improved Binding Affinity to Human Fc Gamma RIIA and Fc Gamma RIIIAs. 28694069 2 39 theme human 410:414 arg1 variants 424:431 aglycosylated human IgG1 Fc variants 396:431 aglycosylated human IgG1 Fc variants 396:431 Previously, we demonstrated that aglycosylated human IgG1 Fc variants can engage the human FcγRII class of the low-affinity hFcγRs, demonstrating that N-linked glycosylation of the Fc is not a strict requirement for hFcγR engagement. 28694069 7 40 dep In 1128:1129 arg1 vivo 1131:1134 vivo 1131:1134 vivo 1131:1134 In vivo tumor control of B16F10 lung metastases further confirmed the variant DTT-IYG to be the best at restoring wild-type-like properties in prevention of lung metastases. 28694069 0 41 theme Binding 66:72 arg1 Affinity 74:81 Wild-Type or Improved Binding Affinity 44:81 Wild-Type or Improved Binding Affinity to Human Fc Gamma RIIA and Fc Gamma RIIIAs 44:124 Engineering Aglycosylated IgG Variants with Wild-Type or Improved Binding Affinity to Human Fc Gamma RIIA and Fc Gamma RIIIAs. 28694069 1 42 theme asparagine 269:278 arg1 297 280:282 asparagine 297 269:282 asparagine 297 of the Fc 269:292 The binding of human IgG1 to human Fc gamma receptors (hFcγRs) is highly sensitive to the presence of a single N-linked glycosylation site at asparagine 297 of the Fc, with deglycosylation resulting in a complete loss of hFcγR binding. 28694069 9 43 theme aglycosylated 1574:1586 arg1 variant 1588:1594 an aglycosylated variant 1571:1594 an aglycosylated variant that may effectively substitute for wild-type Fc 1571:1643 Thus, in this study, we have found an aglycosylated variant that may effectively substitute for wild-type Fc. 28694069 8 44 theme aglycosylated 1515:1527 arg1 N297Q 1529:1533 the aglycosylated N297Q 1511:1533 the aglycosylated N297Q 1511:1533 While deuterium incorporation was similar across most of the protein, several peptides within the CH2 domain of DTT-IYG showed differential deuterium uptake in the peptide region of the FG loop as compared to the aglycosylated N297Q. 28694069 7 45 theme variant 1198:1204 arg1 DTT-IYG 1206:1212 the variant DTT-IYG 1194:1212 the variant DTT-IYG to be the best at restoring wild-type-like properties in prevention of lung metastases 1194:1299 In vivo tumor control of B16F10 lung metastases further confirmed the variant DTT-IYG to be the best at restoring wild-type-like properties in prevention of lung metastases. 28694069 2 46 theme Fc 544:545 arg1 requirement 563:573 a strict requirement 554:573 a strict requirement for hFcγR engagement 554:594 Previously, we demonstrated that aglycosylated human IgG1 Fc variants can engage the human FcγRII class of the low-affinity hFcγRs, demonstrating that N-linked glycosylation of the Fc is not a strict requirement for hFcγR engagement. 28694069 2 46 theme Fc 544:545 arg1 glycosylation 523:535 N-linked glycosylation 514:535 N-linked glycosylation of the Fc 514:545 Previously, we demonstrated that aglycosylated human IgG1 Fc variants can engage the human FcγRII class of the low-affinity hFcγRs, demonstrating that N-linked glycosylation of the Fc is not a strict requirement for hFcγR engagement. 28694069 4 47 theme biophysical 783:793 arg1 properties 795:804 the biophysical properties 779:804 the biophysical properties 779:804 We also assess the biophysical properties and serum half-life of the aglycosylated IgG variants to measure stability. 28694069 9 48 theme wild-type 1632:1640 arg1 Fc 1642:1643 wild-type Fc 1632:1643 wild-type Fc 1632:1643 Thus, in this study, we have found an aglycosylated variant that may effectively substitute for wild-type Fc. 28694069 6 49 theme phagocytosis 1114:1125 arg1 dimers 1082:1087 hFcγRI and hFcγRIIIA dimers 1061:1087 hFcγRI and hFcγRIIIA dimers 1061:1087 A mathematical model of phagocytosis suggests that hFcγRI and hFcγRIIIA dimers were the main drivers of phagocytosis. 28694069 6 49 theme phagocytosis 1114:1125 arg1 drivers 1103:1109 the main drivers 1094:1109 the main drivers of phagocytosis 1094:1125 A mathematical model of phagocytosis suggests that hFcγRI and hFcγRIIIA dimers were the main drivers of phagocytosis. 28694069 1 50 theme IgG1 148:151 arg1 binding 131:137 The binding 127:137 The binding of human IgG1 to human Fc gamma receptors (hFcγRs) 127:188 The binding of human IgG1 to human Fc gamma receptors (hFcγRs) is highly sensitive to the presence of a single N-linked glycosylation site at asparagine 297 of the Fc, with deglycosylation resulting in a complete loss of hFcγR binding. 28694069 1 50 theme IgG1 148:151 arg1 sensitive 200:208 sensitive 200:208 sensitive 200:208 The binding of human IgG1 to human Fc gamma receptors (hFcγRs) is highly sensitive to the presence of a single N-linked glycosylation site at asparagine 297 of the Fc, with deglycosylation resulting in a complete loss of hFcγR binding. 28694069 2 51 theme strict 556:561 arg1 glycosylation 523:535 N-linked glycosylation 514:535 N-linked glycosylation of the Fc 514:545 Previously, we demonstrated that aglycosylated human IgG1 Fc variants can engage the human FcγRII class of the low-affinity hFcγRs, demonstrating that N-linked glycosylation of the Fc is not a strict requirement for hFcγR engagement. 28694069 2 51 theme strict 556:561 arg1 requirement 563:573 a strict requirement 554:573 a strict requirement for hFcγR engagement 554:594 Previously, we demonstrated that aglycosylated human IgG1 Fc variants can engage the human FcγRII class of the low-affinity hFcγRs, demonstrating that N-linked glycosylation of the Fc is not a strict requirement for hFcγR engagement. 28694069 3 52 theme IgG 653:655 arg1 variants 657:664 aglycosylated IgG variants 639:664 aglycosylated IgG variants 639:664 In the present study, we demonstrate that aglycosylated IgG variants can be engineered to productively engage with FcγRIIIA, as well as the human Fc gamma RII subset. 28694069 1 53 theme human 156:160 arg1 receptors 171:179 human Fc gamma receptors 156:179 human Fc gamma receptors (hFcγRs) 156:188 The binding of human IgG1 to human Fc gamma receptors (hFcγRs) is highly sensitive to the presence of a single N-linked glycosylation site at asparagine 297 of the Fc, with deglycosylation resulting in a complete loss of hFcγR binding. 28694069 1 53 theme human 156:160 arg1 hFcγRs 182:187 hFcγRs 182:187 hFcγRs 182:187 The binding of human IgG1 to human Fc gamma receptors (hFcγRs) is highly sensitive to the presence of a single N-linked glycosylation site at asparagine 297 of the Fc, with deglycosylation resulting in a complete loss of hFcγR binding. 28694069 0 54 theme Gamma 113:117 arg1 RIIIAs 119:124 Fc Gamma RIIIAs 110:124 Fc Gamma RIIIAs 110:124 Engineering Aglycosylated IgG Variants with Wild-Type or Improved Binding Affinity to Human Fc Gamma RIIA and Fc Gamma RIIIAs. 28694069 10 55 theme therapeutic 1703:1713 arg1 antibodies 1715:1724 therapeutic antibodies 1703:1724 therapeutic antibodies 1703:1724 These aglycosylated variants have the potential to allow therapeutic antibodies to be produced in virtually any expression system and still maintain effector function. 28694069 1 56 theme gamma 165:169 arg1 receptors 171:179 human Fc gamma receptors 156:179 human Fc gamma receptors (hFcγRs) 156:188 The binding of human IgG1 to human Fc gamma receptors (hFcγRs) is highly sensitive to the presence of a single N-linked glycosylation site at asparagine 297 of the Fc, with deglycosylation resulting in a complete loss of hFcγR binding. 28694069 1 56 theme gamma 165:169 arg1 hFcγRs 182:187 hFcγRs 182:187 hFcγRs 182:187 The binding of human IgG1 to human Fc gamma receptors (hFcγRs) is highly sensitive to the presence of a single N-linked glycosylation site at asparagine 297 of the Fc, with deglycosylation resulting in a complete loss of hFcγR binding. 28694069 2 57 theme hFcγRs 487:492 arg1 class 461:465 the human FcγRII class 444:465 the human FcγRII class of the low-affinity hFcγRs 444:492 Previously, we demonstrated that aglycosylated human IgG1 Fc variants can engage the human FcγRII class of the low-affinity hFcγRs, demonstrating that N-linked glycosylation of the Fc is not a strict requirement for hFcγR engagement. 28694069 1 58 theme complete 331:338 arg1 loss 340:343 a complete loss 329:343 a complete loss of hFcγR binding 329:360 The binding of human IgG1 to human Fc gamma receptors (hFcγRs) is highly sensitive to the presence of a single N-linked glycosylation site at asparagine 297 of the Fc, with deglycosylation resulting in a complete loss of hFcγR binding. 28694069 4 59 theme IgG 847:849 arg1 variants 851:858 the aglycosylated IgG variants 829:858 the aglycosylated IgG variants 829:858 We also assess the biophysical properties and serum half-life of the aglycosylated IgG variants to measure stability. 28694069 7 60 theme tumor 1136:1140 arg1 control 1142:1148 In vivo tumor control 1128:1148 In vivo tumor control of B16F10 lung metastases 1128:1174 In vivo tumor control of B16F10 lung metastases further confirmed the variant DTT-IYG to be the best at restoring wild-type-like properties in prevention of lung metastases. 28694069 1 61 from presence 217:224 arg1 297 280:282 asparagine 297 269:282 asparagine 297 of the Fc 269:292 The binding of human IgG1 to human Fc gamma receptors (hFcγRs) is highly sensitive to the presence of a single N-linked glycosylation site at asparagine 297 of the Fc, with deglycosylation resulting in a complete loss of hFcγR binding. 28694069 2 62 theme N-linked 514:521 arg1 requirement 563:573 a strict requirement 554:573 a strict requirement for hFcγR engagement 554:594 Previously, we demonstrated that aglycosylated human IgG1 Fc variants can engage the human FcγRII class of the low-affinity hFcγRs, demonstrating that N-linked glycosylation of the Fc is not a strict requirement for hFcγR engagement. 28694069 2 62 theme N-linked 514:521 arg1 glycosylation 523:535 N-linked glycosylation 514:535 N-linked glycosylation of the Fc 514:545 Previously, we demonstrated that aglycosylated human IgG1 Fc variants can engage the human FcγRII class of the low-affinity hFcγRs, demonstrating that N-linked glycosylation of the Fc is not a strict requirement for hFcγR engagement. 28694069 8 63 theme DTT-IYG 1414:1420 arg1 DTT-IYG 1414:1420 DTT-IYG 1414:1420 DTT-IYG 1414:1420 While deuterium incorporation was similar across most of the protein, several peptides within the CH2 domain of DTT-IYG showed differential deuterium uptake in the peptide region of the FG loop as compared to the aglycosylated N297Q. 28694069 8 63 theme DTT-IYG 1414:1420 arg1 domain 1404:1409 the CH2 domain 1396:1409 the CH2 domain of DTT-IYG 1396:1420 While deuterium incorporation was similar across most of the protein, several peptides within the CH2 domain of DTT-IYG showed differential deuterium uptake in the peptide region of the FG loop as compared to the aglycosylated N297Q. 28694069 1 64 theme binding 354:360 arg1 loss 340:343 a complete loss 329:343 a complete loss of hFcγR binding 329:360 The binding of human IgG1 to human Fc gamma receptors (hFcγRs) is highly sensitive to the presence of a single N-linked glycosylation site at asparagine 297 of the Fc, with deglycosylation resulting in a complete loss of hFcγR binding. 28694069 8 65 theme differential 1429:1440 arg1 uptake 1452:1457 differential deuterium uptake 1429:1457 differential deuterium uptake in the peptide region of the FG loop 1429:1494 While deuterium incorporation was similar across most of the protein, several peptides within the CH2 domain of DTT-IYG showed differential deuterium uptake in the peptide region of the FG loop as compared to the aglycosylated N297Q. 28694069 5 66 dep constructs 896:905 arg1 constructs 896:905 Aglycosylated constructs 882:905 Aglycosylated constructs N297D/S298T (DTT)-K326I/A327Y/L328G (IYG) and N297D/S298A-IYG 882:967 Aglycosylated constructs N297D/S298T (DTT)-K326I/A327Y/L328G (IYG) and N297D/S298A-IYG optimally drove tumor cell phagocytosis. 28694069 5 66 dep constructs 896:905 arg1 IYG 944:946 IYG 944:946 IYG 944:946 Aglycosylated constructs N297D/S298T (DTT)-K326I/A327Y/L328G (IYG) and N297D/S298A-IYG optimally drove tumor cell phagocytosis. 28694069 5 66 dep constructs 896:905 arg1 N297D/S298A-IYG 953:967 N297D/S298A-IYG 953:967 N297D/S298A-IYG 953:967 Aglycosylated constructs N297D/S298T (DTT)-K326I/A327Y/L328G (IYG) and N297D/S298A-IYG optimally drove tumor cell phagocytosis. 28694069 7 67 theme lung 1160:1163 arg1 metastases 1165:1174 B16F10 lung metastases 1153:1174 B16F10 lung metastases 1153:1174 In vivo tumor control of B16F10 lung metastases further confirmed the variant DTT-IYG to be the best at restoring wild-type-like properties in prevention of lung metastases. 28694069 5 68 theme cell 991:994 arg1 phagocytosis 996:1007 tumor cell phagocytosis 985:1007 tumor cell phagocytosis 985:1007 Aglycosylated constructs N297D/S298T (DTT)-K326I/A327Y/L328G (IYG) and N297D/S298A-IYG optimally drove tumor cell phagocytosis. 28694069 10 69 theme expression 1758:1767 arg1 system 1769:1774 virtually any expression system 1744:1774 virtually any expression system 1744:1774 These aglycosylated variants have the potential to allow therapeutic antibodies to be produced in virtually any expression system and still maintain effector function. 28694069 5 70 gly Aglycosylated 882:894 arg1 constructs 896:905 Aglycosylated constructs 882:905 Aglycosylated constructs N297D/S298T (DTT)-K326I/A327Y/L328G (IYG) and N297D/S298A-IYG 882:967 Aglycosylated constructs N297D/S298T (DTT)-K326I/A327Y/L328G (IYG) and N297D/S298A-IYG optimally drove tumor cell phagocytosis. 28694069 5 70 gly Aglycosylated 882:894 arg1 IYG 944:946 IYG 944:946 IYG 944:946 Aglycosylated constructs N297D/S298T (DTT)-K326I/A327Y/L328G (IYG) and N297D/S298A-IYG optimally drove tumor cell phagocytosis. 28694069 5 70 gly Aglycosylated 882:894 arg1 N297D/S298A-IYG 953:967 N297D/S298A-IYG 953:967 N297D/S298A-IYG 953:967 Aglycosylated constructs N297D/S298T (DTT)-K326I/A327Y/L328G (IYG) and N297D/S298A-IYG optimally drove tumor cell phagocytosis. 28694069 7 71 theme metastases 1290:1299 arg1 prevention 1271:1280 prevention 1271:1280 prevention of lung metastases 1271:1299 In vivo tumor control of B16F10 lung metastases further confirmed the variant DTT-IYG to be the best at restoring wild-type-like properties in prevention of lung metastases. 28694069 0 72 theme Human 86:90 arg1 RIIA 101:104 Human Fc Gamma RIIA 86:104 Human Fc Gamma RIIA 86:104 Engineering Aglycosylated IgG Variants with Wild-Type or Improved Binding Affinity to Human Fc Gamma RIIA and Fc Gamma RIIIAs. 28694069 0 73 theme Gamma 95:99 arg1 RIIA 101:104 Human Fc Gamma RIIA 86:104 Human Fc Gamma RIIA 86:104 Engineering Aglycosylated IgG Variants with Wild-Type or Improved Binding Affinity to Human Fc Gamma RIIA and Fc Gamma RIIIAs. 28694069 5 74 theme Aglycosylated 882:894 arg1 constructs 896:905 Aglycosylated constructs 882:905 Aglycosylated constructs N297D/S298T (DTT)-K326I/A327Y/L328G (IYG) and N297D/S298A-IYG 882:967 Aglycosylated constructs N297D/S298T (DTT)-K326I/A327Y/L328G (IYG) and N297D/S298A-IYG optimally drove tumor cell phagocytosis. 28694069 5 74 theme Aglycosylated 882:894 arg1 IYG 944:946 IYG 944:946 IYG 944:946 Aglycosylated constructs N297D/S298T (DTT)-K326I/A327Y/L328G (IYG) and N297D/S298A-IYG optimally drove tumor cell phagocytosis. 28694069 5 74 theme Aglycosylated 882:894 arg1 N297D/S298A-IYG 953:967 N297D/S298A-IYG 953:967 N297D/S298A-IYG 953:967 Aglycosylated constructs N297D/S298T (DTT)-K326I/A327Y/L328G (IYG) and N297D/S298A-IYG optimally drove tumor cell phagocytosis. 28694069 2 75 theme hFcγR 579:583 arg1 engagement 585:594 hFcγR engagement 579:594 hFcγR engagement 579:594 Previously, we demonstrated that aglycosylated human IgG1 Fc variants can engage the human FcγRII class of the low-affinity hFcγRs, demonstrating that N-linked glycosylation of the Fc is not a strict requirement for hFcγR engagement. 28694069 3 76 theme Fc 743:744 arg1 RII 752:754 the human Fc gamma RII 733:754 the human Fc gamma RII subset 733:761 In the present study, we demonstrate that aglycosylated IgG variants can be engineered to productively engage with FcγRIIIA, as well as the human Fc gamma RII subset. 28694069 7 77 theme In 1128:1129 arg1 control 1142:1148 In vivo tumor control 1128:1148 In vivo tumor control of B16F10 lung metastases 1128:1174 In vivo tumor control of B16F10 lung metastases further confirmed the variant DTT-IYG to be the best at restoring wild-type-like properties in prevention of lung metastases. 28694069 6 78 theme mathematical 1012:1023 arg1 model 1025:1029 A mathematical model 1010:1029 A mathematical model of phagocytosis 1010:1045 A mathematical model of phagocytosis suggests that hFcγRI and hFcγRIIIA dimers were the main drivers of phagocytosis. 28694069 2 79 theme human 448:452 arg1 class 461:465 the human FcγRII class 444:465 the human FcγRII class of the low-affinity hFcγRs 444:492 Previously, we demonstrated that aglycosylated human IgG1 Fc variants can engage the human FcγRII class of the low-affinity hFcγRs, demonstrating that N-linked glycosylation of the Fc is not a strict requirement for hFcγR engagement. 28694069 0 80 theme Aglycosylated 12:24 arg1 Variants 30:37 Aglycosylated IgG Variants 12:37 Aglycosylated IgG Variants 12:37 Engineering Aglycosylated IgG Variants with Wild-Type or Improved Binding Affinity to Human Fc Gamma RIIA and Fc Gamma RIIIAs. 28694069 2 81 theme low-affinity 474:485 arg1 hFcγRs 487:492 the low-affinity hFcγRs 470:492 the low-affinity hFcγRs 470:492 Previously, we demonstrated that aglycosylated human IgG1 Fc variants can engage the human FcγRII class of the low-affinity hFcγRs, demonstrating that N-linked glycosylation of the Fc is not a strict requirement for hFcγR engagement. 28694069 8 82 theme loop 1491:1494 arg1 region 1474:1479 the peptide region 1462:1479 the peptide region of the FG loop 1462:1494 While deuterium incorporation was similar across most of the protein, several peptides within the CH2 domain of DTT-IYG showed differential deuterium uptake in the peptide region of the FG loop as compared to the aglycosylated N297Q. 28694069 8 83 theme deuterium 1308:1316 arg1 incorporation 1318:1330 deuterium incorporation 1308:1330 deuterium incorporation 1308:1330 While deuterium incorporation was similar across most of the protein, several peptides within the CH2 domain of DTT-IYG showed differential deuterium uptake in the peptide region of the FG loop as compared to the aglycosylated N297Q. 28694069 8 84 from uptake 1452:1457 arg1 region 1474:1479 the peptide region 1462:1479 the peptide region of the FG loop 1462:1494 While deuterium incorporation was similar across most of the protein, several peptides within the CH2 domain of DTT-IYG showed differential deuterium uptake in the peptide region of the FG loop as compared to the aglycosylated N297Q. 28694069 1 85 theme single 231:236 arg1 site 261:264 a single N-linked glycosylation site 229:264 a single N-linked glycosylation site at asparagine 297 of the Fc 229:292 The binding of human IgG1 to human Fc gamma receptors (hFcγRs) is highly sensitive to the presence of a single N-linked glycosylation site at asparagine 297 of the Fc, with deglycosylation resulting in a complete loss of hFcγR binding. 28694069 8 86 gly aglycosylated 1515:1527 arg1 N297Q 1529:1533 the aglycosylated N297Q 1511:1533 the aglycosylated N297Q 1511:1533 While deuterium incorporation was similar across most of the protein, several peptides within the CH2 domain of DTT-IYG showed differential deuterium uptake in the peptide region of the FG loop as compared to the aglycosylated N297Q. 28694069 0 87 theme Wild-Type 44:52 arg1 Affinity 74:81 Wild-Type or Improved Binding Affinity 44:81 Wild-Type or Improved Binding Affinity to Human Fc Gamma RIIA and Fc Gamma RIIIAs 44:124 Engineering Aglycosylated IgG Variants with Wild-Type or Improved Binding Affinity to Human Fc Gamma RIIA and Fc Gamma RIIIAs. 28694069 1 88 theme glycosylation 247:259 arg1 site 261:264 a single N-linked glycosylation site 229:264 a single N-linked glycosylation site at asparagine 297 of the Fc 229:292 The binding of human IgG1 to human Fc gamma receptors (hFcγRs) is highly sensitive to the presence of a single N-linked glycosylation site at asparagine 297 of the Fc, with deglycosylation resulting in a complete loss of hFcγR binding. 28694069 2 89 theme IgG1 416:419 arg1 variants 424:431 aglycosylated human IgG1 Fc variants 396:431 aglycosylated human IgG1 Fc variants 396:431 Previously, we demonstrated that aglycosylated human IgG1 Fc variants can engage the human FcγRII class of the low-affinity hFcγRs, demonstrating that N-linked glycosylation of the Fc is not a strict requirement for hFcγR engagement. 28694069 0 90 theme Improved 57:64 arg1 Affinity 74:81 Wild-Type or Improved Binding Affinity 44:81 Wild-Type or Improved Binding Affinity to Human Fc Gamma RIIA and Fc Gamma RIIIAs 44:124 Engineering Aglycosylated IgG Variants with Wild-Type or Improved Binding Affinity to Human Fc Gamma RIIA and Fc Gamma RIIIAs. 28694069 2 91 gly aglycosylated 396:408 arg1 variants 424:431 aglycosylated human IgG1 Fc variants 396:431 aglycosylated human IgG1 Fc variants 396:431 Previously, we demonstrated that aglycosylated human IgG1 Fc variants can engage the human FcγRII class of the low-affinity hFcγRs, demonstrating that N-linked glycosylation of the Fc is not a strict requirement for hFcγR engagement. 28694069 6 92 theme hFcγRIIIA 1072:1080 arg1 dimers 1082:1087 hFcγRI and hFcγRIIIA dimers 1061:1087 hFcγRI and hFcγRIIIA dimers 1061:1087 A mathematical model of phagocytosis suggests that hFcγRI and hFcγRIIIA dimers were the main drivers of phagocytosis. 28694069 6 92 theme hFcγRIIIA 1072:1080 arg1 drivers 1103:1109 the main drivers 1094:1109 the main drivers of phagocytosis 1094:1125 A mathematical model of phagocytosis suggests that hFcγRI and hFcγRIIIA dimers were the main drivers of phagocytosis. 28694069 2 93 theme aglycosylated 396:408 arg1 variants 424:431 aglycosylated human IgG1 Fc variants 396:431 aglycosylated human IgG1 Fc variants 396:431 Previously, we demonstrated that aglycosylated human IgG1 Fc variants can engage the human FcγRII class of the low-affinity hFcγRs, demonstrating that N-linked glycosylation of the Fc is not a strict requirement for hFcγR engagement. 28694069 3 94 theme present 604:610 arg1 study 612:616 the present study 600:616 the present study 600:616 In the present study, we demonstrate that aglycosylated IgG variants can be engineered to productively engage with FcγRIIIA, as well as the human Fc gamma RII subset. 28694069 6 95 theme hFcγRI 1061:1066 arg1 dimers 1082:1087 hFcγRI and hFcγRIIIA dimers 1061:1087 hFcγRI and hFcγRIIIA dimers 1061:1087 A mathematical model of phagocytosis suggests that hFcγRI and hFcγRIIIA dimers were the main drivers of phagocytosis. 28694069 6 95 theme hFcγRI 1061:1066 arg1 drivers 1103:1109 the main drivers 1094:1109 the main drivers of phagocytosis 1094:1125 A mathematical model of phagocytosis suggests that hFcγRI and hFcγRIIIA dimers were the main drivers of phagocytosis. 28694069 1 96 link N-linked 238:245 arg1 site 261:264 a single N-linked glycosylation site 229:264 a single N-linked glycosylation site at asparagine 297 of the Fc 229:292 The binding of human IgG1 to human Fc gamma receptors (hFcγRs) is highly sensitive to the presence of a single N-linked glycosylation site at asparagine 297 of the Fc, with deglycosylation resulting in a complete loss of hFcγR binding. 28694069 6 97 theme phagocytosis 1034:1045 arg1 model 1025:1029 A mathematical model 1010:1029 A mathematical model of phagocytosis 1010:1045 A mathematical model of phagocytosis suggests that hFcγRI and hFcγRIIIA dimers were the main drivers of phagocytosis. 28694069 9 98 gly aglycosylated 1574:1586 arg1 variant 1588:1594 an aglycosylated variant 1571:1594 an aglycosylated variant that may effectively substitute for wild-type Fc 1571:1643 Thus, in this study, we have found an aglycosylated variant that may effectively substitute for wild-type Fc. 28694069 1 99 with sensitive 200:208 arg1 deglycosylation 300:314 deglycosylation 300:314 deglycosylation resulting in a complete loss of hFcγR binding 300:360 The binding of human IgG1 to human Fc gamma receptors (hFcγRs) is highly sensitive to the presence of a single N-linked glycosylation site at asparagine 297 of the Fc, with deglycosylation resulting in a complete loss of hFcγR binding. 28694069 8 100 theme several 1372:1378 arg1 peptides 1380:1387 several peptides 1372:1387 several peptides within the CH2 domain of DTT-IYG 1372:1420 While deuterium incorporation was similar across most of the protein, several peptides within the CH2 domain of DTT-IYG showed differential deuterium uptake in the peptide region of the FG loop as compared to the aglycosylated N297Q. 28694069 10 101 theme aglycosylated 1652:1664 arg1 variants 1666:1673 These aglycosylated variants 1646:1673 These aglycosylated variants 1646:1673 These aglycosylated variants have the potential to allow therapeutic antibodies to be produced in virtually any expression system and still maintain effector function. 28782088 8 0 theme unknown 1288:1294 arg1 ligand 1296:1301 a yet unknown ligand 1282:1301 a yet unknown ligand on the plasma membrane of mastocytoma cells 1282:1345 Interestingly, reconstitution of N-linked glycosylation enabled secretion of a mNKp30-Fc fusion protein which recognized a yet unknown ligand on the plasma membrane of mastocytoma cells. 28782088 3 1 contain contains 464:471 arg2 codons 492:497 two premature stop codons 473:497 two premature stop codons 473:497 However, in contrast to other higher vertebrates, NKp30 is only a pseudogene in mouse, which contains two premature stop codons. 28782088 3 1 contain contains 464:471 arg1 NKp30 421:425 NKp30 421:425 NKp30 421:425 However, in contrast to other higher vertebrates, NKp30 is only a pseudogene in mouse, which contains two premature stop codons. 28782088 3 1 contain contains 464:471 arg1 pseudogene 437:446 a pseudogene 435:446 a pseudogene 435:446 However, in contrast to other higher vertebrates, NKp30 is only a pseudogene in mouse, which contains two premature stop codons. 28782088 2 2 theme ancient 344:350 arg1 receptors 360:368 the most ancient NK cell receptors 335:368 the most ancient NK cell receptors 335:368 Phylogenetic analyses showed that NKp30 is highly conserved in almost all jawed vertebrates and thus, represents one of the most ancient NK cell receptors. 28782088 6 3 theme membrane 961:968 arg1 targeting 970:978 plasma membrane targeting 954:978 plasma membrane targeting 954:978 Previous studies implicated that N-linked glycosylation is crucial for plasma membrane targeting and ligand binding of human NKp30. 28782088 4 4 from receptor 722:729 arg1 cells 750:754 A5-GFP reporter cells 734:754 A5-GFP reporter cells 734:754 To decipher the evolutionary role and biological function of NKp30 in mouse, we removed these premature stop codons and expressed the putative mouse NKp30 (mNKp30) protein as soluble Fc fusion construct and as full-length receptor on A5-GFP reporter cells. 28782088 1 5 theme fundamental 150:160 arg1 role 162:165 a fundamental role 148:165 a fundamental role 148:165 The activating natural cytotoxicity receptors on natural killer (NK) cells play a fundamental role in immunosurveillance of infections and cancer. 28782088 8 6 from ligand 1296:1301 arg1 membrane 1317:1324 the plasma membrane 1306:1324 the plasma membrane of mastocytoma cells 1306:1345 Interestingly, reconstitution of N-linked glycosylation enabled secretion of a mNKp30-Fc fusion protein which recognized a yet unknown ligand on the plasma membrane of mastocytoma cells. 28782088 4 7 theme biological 538:547 arg1 function 549:556 biological function 538:556 biological function 538:556 To decipher the evolutionary role and biological function of NKp30 in mouse, we removed these premature stop codons and expressed the putative mouse NKp30 (mNKp30) protein as soluble Fc fusion construct and as full-length receptor on A5-GFP reporter cells. 28782088 8 8 theme cells 1341:1345 arg1 membrane 1317:1324 the plasma membrane 1306:1324 the plasma membrane of mastocytoma cells 1306:1345 Interestingly, reconstitution of N-linked glycosylation enabled secretion of a mNKp30-Fc fusion protein which recognized a yet unknown ligand on the plasma membrane of mastocytoma cells. 28782088 7 9 theme jawed 1057:1061 arg1 vertebrates 1063:1073 all other jawed vertebrates 1047:1073 all other jawed vertebrates analyzed so far 1047:1089 However, even though present in all other jawed vertebrates analyzed so far, these three N-linked glycosylation sites are missing in mouse NKp30. 28782088 4 10 theme putative 634:641 arg1 protein 664:670 the putative mouse NKp30 (mNKp30) protein 630:670 the putative mouse NKp30 (mNKp30) protein as soluble Fc fusion construct and as full-length receptor on A5-GFP reporter cells 630:754 To decipher the evolutionary role and biological function of NKp30 in mouse, we removed these premature stop codons and expressed the putative mouse NKp30 (mNKp30) protein as soluble Fc fusion construct and as full-length receptor on A5-GFP reporter cells. 28782088 2 11 theme jawed 289:293 arg1 vertebrates 295:305 almost all jawed vertebrates 278:305 almost all jawed vertebrates 278:305 Phylogenetic analyses showed that NKp30 is highly conserved in almost all jawed vertebrates and thus, represents one of the most ancient NK cell receptors. 28782088 4 12 theme fusion 686:691 arg1 construct 693:701 soluble Fc fusion construct 675:701 soluble Fc fusion construct 675:701 To decipher the evolutionary role and biological function of NKp30 in mouse, we removed these premature stop codons and expressed the putative mouse NKp30 (mNKp30) protein as soluble Fc fusion construct and as full-length receptor on A5-GFP reporter cells. 28782088 4 13 theme NKp30 561:565 arg1 role 529:532 evolutionary role 516:532 evolutionary role 516:532 To decipher the evolutionary role and biological function of NKp30 in mouse, we removed these premature stop codons and expressed the putative mouse NKp30 (mNKp30) protein as soluble Fc fusion construct and as full-length receptor on A5-GFP reporter cells. 28782088 4 13 theme NKp30 561:565 arg1 function 549:556 biological function 538:556 biological function 538:556 To decipher the evolutionary role and biological function of NKp30 in mouse, we removed these premature stop codons and expressed the putative mouse NKp30 (mNKp30) protein as soluble Fc fusion construct and as full-length receptor on A5-GFP reporter cells. 28782088 4 14 theme Fc 683:684 arg1 construct 693:701 soluble Fc fusion construct 675:701 soluble Fc fusion construct 675:701 To decipher the evolutionary role and biological function of NKp30 in mouse, we removed these premature stop codons and expressed the putative mouse NKp30 (mNKp30) protein as soluble Fc fusion construct and as full-length receptor on A5-GFP reporter cells. 28782088 9 15 theme species-specific 1517:1532 arg1 loss 1534:1537 a species-specific loss 1515:1537 a species-specific loss of function 1515:1549 Based on these data, our study is the first to show expression and functional analysis of a mNKp30 protein suggesting that the mouse NKp30 pseudogene is the result of a species-specific loss of function. 28782088 4 16 theme mouse 643:647 arg1 protein 664:670 the putative mouse NKp30 (mNKp30) protein 630:670 the putative mouse NKp30 (mNKp30) protein as soluble Fc fusion construct and as full-length receptor on A5-GFP reporter cells 630:754 To decipher the evolutionary role and biological function of NKp30 in mouse, we removed these premature stop codons and expressed the putative mouse NKp30 (mNKp30) protein as soluble Fc fusion construct and as full-length receptor on A5-GFP reporter cells. 28782088 2 17 theme all 285:287 arg1 vertebrates 295:305 almost all jawed vertebrates 278:305 almost all jawed vertebrates 278:305 Phylogenetic analyses showed that NKp30 is highly conserved in almost all jawed vertebrates and thus, represents one of the most ancient NK cell receptors. 28782088 9 18 theme protein 1447:1453 arg1 expression 1400:1409 expression 1400:1409 expression 1400:1409 Based on these data, our study is the first to show expression and functional analysis of a mNKp30 protein suggesting that the mouse NKp30 pseudogene is the result of a species-specific loss of function. 28782088 9 18 theme protein 1447:1453 arg1 analysis 1426:1433 functional analysis 1415:1433 functional analysis of a mNKp30 protein suggesting that the mouse NKp30 pseudogene is the result of a species-specific loss of function 1415:1549 Based on these data, our study is the first to show expression and functional analysis of a mNKp30 protein suggesting that the mouse NKp30 pseudogene is the result of a species-specific loss of function. 28782088 4 19 from function 549:556 arg1 mouse 570:574 mouse 570:574 mouse 570:574 To decipher the evolutionary role and biological function of NKp30 in mouse, we removed these premature stop codons and expressed the putative mouse NKp30 (mNKp30) protein as soluble Fc fusion construct and as full-length receptor on A5-GFP reporter cells. 28782088 4 20 dep role 529:532 arg1 the 512:514 the 512:514 the 512:514 To decipher the evolutionary role and biological function of NKp30 in mouse, we removed these premature stop codons and expressed the putative mouse NKp30 (mNKp30) protein as soluble Fc fusion construct and as full-length receptor on A5-GFP reporter cells. 28782088 1 21 theme activating 72:81 arg1 receptors 104:112 The activating natural cytotoxicity receptors 68:112 The activating natural cytotoxicity receptors on natural killer (NK) cells 68:141 The activating natural cytotoxicity receptors on natural killer (NK) cells play a fundamental role in immunosurveillance of infections and cancer. 28782088 8 22 theme N-linked 1194:1201 arg1 glycosylation 1203:1215 N-linked glycosylation 1194:1215 N-linked glycosylation 1194:1215 Interestingly, reconstitution of N-linked glycosylation enabled secretion of a mNKp30-Fc fusion protein which recognized a yet unknown ligand on the plasma membrane of mastocytoma cells. 28782088 7 23 theme other 1051:1055 arg1 vertebrates 1063:1073 all other jawed vertebrates 1047:1073 all other jawed vertebrates analyzed so far 1047:1089 However, even though present in all other jawed vertebrates analyzed so far, these three N-linked glycosylation sites are missing in mouse NKp30. 28782088 8 24 theme protein 1257:1263 arg1 secretion 1225:1233 secretion 1225:1233 secretion of a mNKp30-Fc fusion protein which recognized a yet unknown ligand on the plasma membrane of mastocytoma cells 1225:1345 Interestingly, reconstitution of N-linked glycosylation enabled secretion of a mNKp30-Fc fusion protein which recognized a yet unknown ligand on the plasma membrane of mastocytoma cells. 28782088 1 25 theme natural 83:89 arg1 receptors 104:112 The activating natural cytotoxicity receptors 68:112 The activating natural cytotoxicity receptors on natural killer (NK) cells 68:141 The activating natural cytotoxicity receptors on natural killer (NK) cells play a fundamental role in immunosurveillance of infections and cancer. 28782088 8 26 link N-linked 1194:1201 arg1 glycosylation 1203:1215 N-linked glycosylation 1194:1215 N-linked glycosylation 1194:1215 Interestingly, reconstitution of N-linked glycosylation enabled secretion of a mNKp30-Fc fusion protein which recognized a yet unknown ligand on the plasma membrane of mastocytoma cells. 28782088 1 27 theme cytotoxicity 91:102 arg1 receptors 104:112 The activating natural cytotoxicity receptors 68:112 The activating natural cytotoxicity receptors on natural killer (NK) cells 68:141 The activating natural cytotoxicity receptors on natural killer (NK) cells play a fundamental role in immunosurveillance of infections and cancer. 28782088 9 28 theme functional 1415:1424 arg1 analysis 1426:1433 functional analysis 1415:1433 functional analysis of a mNKp30 protein suggesting that the mouse NKp30 pseudogene is the result of a species-specific loss of function 1415:1549 Based on these data, our study is the first to show expression and functional analysis of a mNKp30 protein suggesting that the mouse NKp30 pseudogene is the result of a species-specific loss of function. 28782088 3 29 theme higher 401:406 arg1 vertebrates 408:418 other higher vertebrates 395:418 other higher vertebrates 395:418 However, in contrast to other higher vertebrates, NKp30 is only a pseudogene in mouse, which contains two premature stop codons. 28782088 4 30 from role 529:532 arg1 mouse 570:574 mouse 570:574 mouse 570:574 To decipher the evolutionary role and biological function of NKp30 in mouse, we removed these premature stop codons and expressed the putative mouse NKp30 (mNKp30) protein as soluble Fc fusion construct and as full-length receptor on A5-GFP reporter cells. 28782088 4 31 theme evolutionary 516:527 arg1 role 529:532 evolutionary role 516:532 evolutionary role 516:532 To decipher the evolutionary role and biological function of NKp30 in mouse, we removed these premature stop codons and expressed the putative mouse NKp30 (mNKp30) protein as soluble Fc fusion construct and as full-length receptor on A5-GFP reporter cells. 28782088 4 32 theme soluble 675:681 arg1 construct 693:701 soluble Fc fusion construct 675:701 soluble Fc fusion construct 675:701 To decipher the evolutionary role and biological function of NKp30 in mouse, we removed these premature stop codons and expressed the putative mouse NKp30 (mNKp30) protein as soluble Fc fusion construct and as full-length receptor on A5-GFP reporter cells. 28782088 2 33 theme receptors 360:368 arg1 receptors 360:368 the most ancient NK cell receptors 335:368 the most ancient NK cell receptors 335:368 Phylogenetic analyses showed that NKp30 is highly conserved in almost all jawed vertebrates and thus, represents one of the most ancient NK cell receptors. 28782088 2 33 theme receptors 360:368 arg1 one 328:330 one 328:330 one 328:330 Phylogenetic analyses showed that NKp30 is highly conserved in almost all jawed vertebrates and thus, represents one of the most ancient NK cell receptors. 28782088 0 34 theme ligand-binding 20:33 arg1 receptor 58:65 a ligand-binding competent murine NKp30 receptor 18:65 a ligand-binding competent murine NKp30 receptor 18:65 Reconstitution of a ligand-binding competent murine NKp30 receptor. 28782088 6 35 theme human 1002:1006 arg1 targeting 970:978 plasma membrane targeting 954:978 plasma membrane targeting 954:978 Previous studies implicated that N-linked glycosylation is crucial for plasma membrane targeting and ligand binding of human NKp30. 28782088 6 35 theme human 1002:1006 arg1 binding 991:997 ligand binding 984:997 ligand binding of human NKp30 984:1012 Previous studies implicated that N-linked glycosylation is crucial for plasma membrane targeting and ligand binding of human NKp30. 28782088 9 36 theme loss 1534:1537 arg1 pseudogene 1487:1496 the mouse NKp30 pseudogene 1471:1496 the mouse NKp30 pseudogene 1471:1496 Based on these data, our study is the first to show expression and functional analysis of a mNKp30 protein suggesting that the mouse NKp30 pseudogene is the result of a species-specific loss of function. 28782088 9 36 theme loss 1534:1537 arg1 result 1505:1510 the result 1501:1510 the result of a species-specific loss of function 1501:1549 Based on these data, our study is the first to show expression and functional analysis of a mNKp30 protein suggesting that the mouse NKp30 pseudogene is the result of a species-specific loss of function. 28782088 1 37 theme infections 192:201 arg1 immunosurveillance 170:187 immunosurveillance 170:187 immunosurveillance of infections and cancer 170:212 The activating natural cytotoxicity receptors on natural killer (NK) cells play a fundamental role in immunosurveillance of infections and cancer. 28782088 7 38 theme glycosylation 1113:1125 arg1 sites 1127:1131 these three N-linked glycosylation sites 1092:1131 these three N-linked glycosylation sites 1092:1131 However, even though present in all other jawed vertebrates analyzed so far, these three N-linked glycosylation sites are missing in mouse NKp30. 28782088 6 39 theme N-linked 916:923 arg1 glycosylation 925:937 N-linked glycosylation 916:937 N-linked glycosylation 916:937 Previous studies implicated that N-linked glycosylation is crucial for plasma membrane targeting and ligand binding of human NKp30. 28782088 7 40 from missing 1137:1143 arg1 mouse 1148:1152 mouse NKp30 1148:1158 mouse NKp30 1148:1158 However, even though present in all other jawed vertebrates analyzed so far, these three N-linked glycosylation sites are missing in mouse NKp30. 28782088 1 41 theme natural 117:123 arg1 NK 133:134 NK 133:134 NK 133:134 The activating natural cytotoxicity receptors on natural killer (NK) cells play a fundamental role in immunosurveillance of infections and cancer. 28782088 1 41 theme natural 117:123 arg1 killer 125:130 natural killer 117:130 natural killer (NK) cells 117:141 The activating natural cytotoxicity receptors on natural killer (NK) cells play a fundamental role in immunosurveillance of infections and cancer. 28782088 9 42 theme mouse 1475:1479 arg1 pseudogene 1487:1496 the mouse NKp30 pseudogene 1471:1496 the mouse NKp30 pseudogene 1471:1496 Based on these data, our study is the first to show expression and functional analysis of a mNKp30 protein suggesting that the mouse NKp30 pseudogene is the result of a species-specific loss of function. 28782088 9 42 theme mouse 1475:1479 arg1 result 1505:1510 the result 1501:1510 the result of a species-specific loss of function 1501:1549 Based on these data, our study is the first to show expression and functional analysis of a mNKp30 protein suggesting that the mouse NKp30 pseudogene is the result of a species-specific loss of function. 28782088 3 43 theme premature 477:485 arg1 codons 492:497 two premature stop codons 473:497 two premature stop codons 473:497 However, in contrast to other higher vertebrates, NKp30 is only a pseudogene in mouse, which contains two premature stop codons. 28782088 0 44 theme murine 45:50 arg1 receptor 58:65 a ligand-binding competent murine NKp30 receptor 18:65 a ligand-binding competent murine NKp30 receptor 18:65 Reconstitution of a ligand-binding competent murine NKp30 receptor. 28782088 8 45 theme fusion 1250:1255 arg1 protein 1257:1263 a mNKp30-Fc fusion protein 1238:1263 a mNKp30-Fc fusion protein which recognized a yet unknown ligand on the plasma membrane of mastocytoma cells 1238:1345 Interestingly, reconstitution of N-linked glycosylation enabled secretion of a mNKp30-Fc fusion protein which recognized a yet unknown ligand on the plasma membrane of mastocytoma cells. 28782088 4 46 theme stop 604:607 arg1 codons 609:614 these premature stop codons 588:614 these premature stop codons 588:614 To decipher the evolutionary role and biological function of NKp30 in mouse, we removed these premature stop codons and expressed the putative mouse NKp30 (mNKp30) protein as soluble Fc fusion construct and as full-length receptor on A5-GFP reporter cells. 28782088 6 47 link N-linked 916:923 arg1 glycosylation 925:937 N-linked glycosylation 916:937 N-linked glycosylation 916:937 Previous studies implicated that N-linked glycosylation is crucial for plasma membrane targeting and ligand binding of human NKp30. 28782088 8 48 theme glycosylation 1203:1215 arg1 reconstitution 1176:1189 reconstitution 1176:1189 reconstitution of N-linked glycosylation 1176:1215 Interestingly, reconstitution of N-linked glycosylation enabled secretion of a mNKp30-Fc fusion protein which recognized a yet unknown ligand on the plasma membrane of mastocytoma cells. 28782088 1 49 theme cancer 207:212 arg1 immunosurveillance 170:187 immunosurveillance 170:187 immunosurveillance of infections and cancer 170:212 The activating natural cytotoxicity receptors on natural killer (NK) cells play a fundamental role in immunosurveillance of infections and cancer. 28782088 0 50 theme competent 35:43 arg1 receptor 58:65 a ligand-binding competent murine NKp30 receptor 18:65 a ligand-binding competent murine NKp30 receptor 18:65 Reconstitution of a ligand-binding competent murine NKp30 receptor. 28782088 3 51 theme other 395:399 arg1 vertebrates 408:418 other higher vertebrates 395:418 other higher vertebrates 395:418 However, in contrast to other higher vertebrates, NKp30 is only a pseudogene in mouse, which contains two premature stop codons. 28782088 6 52 theme plasma 954:959 arg1 targeting 970:978 plasma membrane targeting 954:978 plasma membrane targeting 954:978 Previous studies implicated that N-linked glycosylation is crucial for plasma membrane targeting and ligand binding of human NKp30. 28782088 3 53 dep vertebrates 408:418 arg1 contrast 383:390 contrast 383:390 contrast 383:390 However, in contrast to other higher vertebrates, NKp30 is only a pseudogene in mouse, which contains two premature stop codons. 28782088 4 54 theme premature 594:602 arg1 codons 609:614 these premature stop codons 588:614 these premature stop codons 588:614 To decipher the evolutionary role and biological function of NKp30 in mouse, we removed these premature stop codons and expressed the putative mouse NKp30 (mNKp30) protein as soluble Fc fusion construct and as full-length receptor on A5-GFP reporter cells. 28782088 0 55 theme receptor 58:65 arg1 Reconstitution 0:13 Reconstitution 0:13 Reconstitution of a ligand-binding competent murine NKp30 receptor 0:65 Reconstitution of a ligand-binding competent murine NKp30 receptor. 28782088 8 56 theme mastocytoma 1329:1339 arg1 cells 1341:1345 mastocytoma cells 1329:1345 mastocytoma cells 1329:1345 Interestingly, reconstitution of N-linked glycosylation enabled secretion of a mNKp30-Fc fusion protein which recognized a yet unknown ligand on the plasma membrane of mastocytoma cells. 28782088 9 57 theme function 1542:1549 arg1 loss 1534:1537 a species-specific loss 1515:1537 a species-specific loss of function 1515:1549 Based on these data, our study is the first to show expression and functional analysis of a mNKp30 protein suggesting that the mouse NKp30 pseudogene is the result of a species-specific loss of function. 28782088 1 58 theme killer 125:130 arg1 cells 137:141 natural killer (NK) cells 117:141 natural killer (NK) cells 117:141 The activating natural cytotoxicity receptors on natural killer (NK) cells play a fundamental role in immunosurveillance of infections and cancer. 28782088 6 59 theme Previous 883:890 arg1 studies 892:898 Previous studies 883:898 Previous studies 883:898 Previous studies implicated that N-linked glycosylation is crucial for plasma membrane targeting and ligand binding of human NKp30. 28782088 2 60 theme Phylogenetic 215:226 arg1 analyses 228:235 Phylogenetic analyses 215:235 Phylogenetic analyses 215:235 Phylogenetic analyses showed that NKp30 is highly conserved in almost all jawed vertebrates and thus, represents one of the most ancient NK cell receptors. 28782088 7 61 from mouse 1148:1152 arg1 missing 1137:1143 missing 1137:1143 missing 1137:1143 However, even though present in all other jawed vertebrates analyzed so far, these three N-linked glycosylation sites are missing in mouse NKp30. 28782088 7 62 theme N-linked 1104:1111 arg1 sites 1127:1131 these three N-linked glycosylation sites 1092:1131 these three N-linked glycosylation sites 1092:1131 However, even though present in all other jawed vertebrates analyzed so far, these three N-linked glycosylation sites are missing in mouse NKp30. 28782088 8 63 theme mNKp30-Fc 1240:1248 arg1 protein 1257:1263 a mNKp30-Fc fusion protein 1238:1263 a mNKp30-Fc fusion protein which recognized a yet unknown ligand on the plasma membrane of mastocytoma cells 1238:1345 Interestingly, reconstitution of N-linked glycosylation enabled secretion of a mNKp30-Fc fusion protein which recognized a yet unknown ligand on the plasma membrane of mastocytoma cells. 28782088 7 64 link N-linked 1104:1111 arg1 sites 1127:1131 these three N-linked glycosylation sites 1092:1131 these three N-linked glycosylation sites 1092:1131 However, even though present in all other jawed vertebrates analyzed so far, these three N-linked glycosylation sites are missing in mouse NKp30. 28782088 4 65 theme A5-GFP 734:739 arg1 cells 750:754 A5-GFP reporter cells 734:754 A5-GFP reporter cells 734:754 To decipher the evolutionary role and biological function of NKp30 in mouse, we removed these premature stop codons and expressed the putative mouse NKp30 (mNKp30) protein as soluble Fc fusion construct and as full-length receptor on A5-GFP reporter cells. 28782088 3 66 from pseudogene 437:446 arg1 mouse 451:455 mouse 451:455 mouse 451:455 However, in contrast to other higher vertebrates, NKp30 is only a pseudogene in mouse, which contains two premature stop codons. 28782088 9 67 theme mNKp30 1440:1445 arg1 protein 1447:1453 a mNKp30 protein 1438:1453 a mNKp30 protein suggesting that the mouse NKp30 pseudogene is the result of a species-specific loss of function 1438:1549 Based on these data, our study is the first to show expression and functional analysis of a mNKp30 protein suggesting that the mouse NKp30 pseudogene is the result of a species-specific loss of function. 28782088 8 68 theme plasma 1310:1315 arg1 membrane 1317:1324 the plasma membrane 1306:1324 the plasma membrane of mastocytoma cells 1306:1345 Interestingly, reconstitution of N-linked glycosylation enabled secretion of a mNKp30-Fc fusion protein which recognized a yet unknown ligand on the plasma membrane of mastocytoma cells. 28782088 4 69 theme full-length 710:720 arg1 receptor 722:729 full-length receptor 710:729 full-length receptor on A5-GFP reporter cells 710:754 To decipher the evolutionary role and biological function of NKp30 in mouse, we removed these premature stop codons and expressed the putative mouse NKp30 (mNKp30) protein as soluble Fc fusion construct and as full-length receptor on A5-GFP reporter cells. 28782088 5 70 theme plasma 852:857 arg1 membrane 859:866 the plasma membrane 848:866 the plasma membrane 848:866 Interestingly, even though both NKp30 variants were expressed, maturation and targeting to the plasma membrane were impaired. 28782088 2 71 theme NK 352:353 arg1 receptors 360:368 the most ancient NK cell receptors 335:368 the most ancient NK cell receptors 335:368 Phylogenetic analyses showed that NKp30 is highly conserved in almost all jawed vertebrates and thus, represents one of the most ancient NK cell receptors. 28782088 6 72 theme ligand 984:989 arg1 binding 991:997 ligand binding 984:997 ligand binding of human NKp30 984:1012 Previous studies implicated that N-linked glycosylation is crucial for plasma membrane targeting and ligand binding of human NKp30. 28782088 7 73 gly glycosylation 1113:1125 arg2 sites 1127:1131 these three N-linked glycosylation sites 1092:1131 these three N-linked glycosylation sites 1092:1131 However, even though present in all other jawed vertebrates analyzed so far, these three N-linked glycosylation sites are missing in mouse NKp30. 28782088 7 73 gly glycosylation 1113:1125 arg2 three 1098:1102 three 1098:1102 three 1098:1102 However, even though present in all other jawed vertebrates analyzed so far, these three N-linked glycosylation sites are missing in mouse NKp30. 28782088 2 74 theme cell 355:358 arg1 receptors 360:368 the most ancient NK cell receptors 335:368 the most ancient NK cell receptors 335:368 Phylogenetic analyses showed that NKp30 is highly conserved in almost all jawed vertebrates and thus, represents one of the most ancient NK cell receptors. 28782088 1 75 from receptors 104:112 arg1 cells 137:141 natural killer (NK) cells 117:141 natural killer (NK) cells 117:141 The activating natural cytotoxicity receptors on natural killer (NK) cells play a fundamental role in immunosurveillance of infections and cancer. 28782088 4 76 theme reporter 741:748 arg1 cells 750:754 A5-GFP reporter cells 734:754 A5-GFP reporter cells 734:754 To decipher the evolutionary role and biological function of NKp30 in mouse, we removed these premature stop codons and expressed the putative mouse NKp30 (mNKp30) protein as soluble Fc fusion construct and as full-length receptor on A5-GFP reporter cells. 28782088 3 77 theme stop 487:490 arg1 codons 492:497 two premature stop codons 473:497 two premature stop codons 473:497 However, in contrast to other higher vertebrates, NKp30 is only a pseudogene in mouse, which contains two premature stop codons. 25617829 4 0 theme extracellular 763:775 arg1 domain 792:797 the extracellular amino-terminal domain 759:797 the extracellular amino-terminal domain 759:797 GPRC6A has been speculated to form covalently linked dimers through cysteine disulfide linkage in the extracellular amino-terminal domain and here we show that GPRC6A indeed is a homodimer and that a disulfide bridge between the C131 residues is formed. 25617829 4 1 from linkage 748:754 arg1 domain 792:797 the extracellular amino-terminal domain 759:797 the extracellular amino-terminal domain 759:797 GPRC6A has been speculated to form covalently linked dimers through cysteine disulfide linkage in the extracellular amino-terminal domain and here we show that GPRC6A indeed is a homodimer and that a disulfide bridge between the C131 residues is formed. 25617829 4 2 theme linked 707:712 arg1 dimers 714:719 covalently linked dimers 696:719 covalently linked dimers 696:719 GPRC6A has been speculated to form covalently linked dimers through cysteine disulfide linkage in the extracellular amino-terminal domain and here we show that GPRC6A indeed is a homodimer and that a disulfide bridge between the C131 residues is formed. 25617829 4 3 theme disulfide 738:746 arg1 linkage 748:754 cysteine disulfide linkage 729:754 cysteine disulfide linkage in the extracellular amino-terminal domain 729:797 GPRC6A has been speculated to form covalently linked dimers through cysteine disulfide linkage in the extracellular amino-terminal domain and here we show that GPRC6A indeed is a homodimer and that a disulfide bridge between the C131 residues is formed. 25617829 3 4 theme surface 582:588 arg1 expression 590:599 surface expression 582:599 surface expression 582:599 Herein, we show that the nutrient-sensing class C G protein-coupled receptor GPRC6A carries seven N-glycans and that one of these sites modulates surface expression whereas mutation of another site affects receptor function. 25617829 3 5 theme nutrient-sensing 461:476 arg1 GPRC6A 513:518 the nutrient-sensing class C G protein-coupled receptor GPRC6A 457:518 the nutrient-sensing class C G protein-coupled receptor GPRC6A 457:518 Herein, we show that the nutrient-sensing class C G protein-coupled receptor GPRC6A carries seven N-glycans and that one of these sites modulates surface expression whereas mutation of another site affects receptor function. 25617829 3 6 theme site 629:632 arg1 mutation 609:616 mutation 609:616 mutation of another site 609:632 Herein, we show that the nutrient-sensing class C G protein-coupled receptor GPRC6A carries seven N-glycans and that one of these sites modulates surface expression whereas mutation of another site affects receptor function. 25617829 1 7 theme receptor 211:218 arg1 pharmacology 220:231 receptor pharmacology 211:231 receptor pharmacology 211:231 Investigation of post-translational modifications of receptor proteins is important for our understanding of receptor pharmacology and disease physiology. 25617829 2 8 theme receptors 348:356 arg1 modifications 305:317 post-translational modifications 286:317 post-translational modifications of class C G protein-coupled receptors 286:356 However, our knowledge about post-translational modifications of class C G protein-coupled receptors and how these modifications regulate expression and function is very limited. 25617829 1 9 theme pharmacology 220:231 arg1 understanding 194:206 our understanding 190:206 our understanding of receptor pharmacology and disease physiology 190:254 Investigation of post-translational modifications of receptor proteins is important for our understanding of receptor pharmacology and disease physiology. 25617829 0 10 theme disulfide 20:28 arg1 bonding 30:36 disulfide bonding 20:36 disulfide bonding 20:36 N-glycosylation and disulfide bonding affects GPRC6A receptor expression, function, and dimerization. 25617829 2 11 theme protein-coupled 332:346 arg1 receptors 348:356 class C G protein-coupled receptors 322:356 class C G protein-coupled receptors 322:356 However, our knowledge about post-translational modifications of class C G protein-coupled receptors and how these modifications regulate expression and function is very limited. 25617829 0 12 theme GPRC6A 46:51 arg1 expression 62:71 GPRC6A receptor expression 46:71 GPRC6A receptor expression 46:71 N-glycosylation and disulfide bonding affects GPRC6A receptor expression, function, and dimerization. 25617829 4 13 theme amino-terminal 777:790 arg1 domain 792:797 the extracellular amino-terminal domain 759:797 the extracellular amino-terminal domain 759:797 GPRC6A has been speculated to form covalently linked dimers through cysteine disulfide linkage in the extracellular amino-terminal domain and here we show that GPRC6A indeed is a homodimer and that a disulfide bridge between the C131 residues is formed. 25617829 3 14 theme protein-coupled 488:502 arg1 GPRC6A 513:518 the nutrient-sensing class C G protein-coupled receptor GPRC6A 457:518 the nutrient-sensing class C G protein-coupled receptor GPRC6A 457:518 Herein, we show that the nutrient-sensing class C G protein-coupled receptor GPRC6A carries seven N-glycans and that one of these sites modulates surface expression whereas mutation of another site affects receptor function. 25617829 0 15 gly N-glycosylation 0:14 arg1 GPRC6A 46:51 GPRC6A receptor expression 46:71 GPRC6A receptor expression 46:71 N-glycosylation and disulfide bonding affects GPRC6A receptor expression, function, and dimerization. 25617829 0 15 gly N-glycosylation 0:14 arg1 receptor 53:60 GPRC6A receptor expression 46:71 GPRC6A receptor expression 46:71 N-glycosylation and disulfide bonding affects GPRC6A receptor expression, function, and dimerization. 25617829 4 16 theme cysteine 729:736 arg1 linkage 748:754 cysteine disulfide linkage 729:754 cysteine disulfide linkage in the extracellular amino-terminal domain 729:797 GPRC6A has been speculated to form covalently linked dimers through cysteine disulfide linkage in the extracellular amino-terminal domain and here we show that GPRC6A indeed is a homodimer and that a disulfide bridge between the C131 residues is formed. 25617829 1 17 theme disease 237:243 arg1 physiology 245:254 disease physiology 237:254 disease physiology 237:254 Investigation of post-translational modifications of receptor proteins is important for our understanding of receptor pharmacology and disease physiology. 25617829 3 18 contain carries 520:526 arg1 GPRC6A 513:518 the nutrient-sensing class C G protein-coupled receptor GPRC6A 457:518 the nutrient-sensing class C G protein-coupled receptor GPRC6A 457:518 Herein, we show that the nutrient-sensing class C G protein-coupled receptor GPRC6A carries seven N-glycans and that one of these sites modulates surface expression whereas mutation of another site affects receptor function. 25617829 3 18 contain carries 520:526 arg2 N-glycans 534:542 seven N-glycans 528:542 seven N-glycans 528:542 Herein, we show that the nutrient-sensing class C G protein-coupled receptor GPRC6A carries seven N-glycans and that one of these sites modulates surface expression whereas mutation of another site affects receptor function. 25617829 3 19 theme receptor 504:511 arg1 GPRC6A 513:518 the nutrient-sensing class C G protein-coupled receptor GPRC6A 457:518 the nutrient-sensing class C G protein-coupled receptor GPRC6A 457:518 Herein, we show that the nutrient-sensing class C G protein-coupled receptor GPRC6A carries seven N-glycans and that one of these sites modulates surface expression whereas mutation of another site affects receptor function. 25617829 1 20 theme post-translational 119:136 arg1 modifications 138:150 post-translational modifications 119:150 post-translational modifications of receptor proteins 119:171 Investigation of post-translational modifications of receptor proteins is important for our understanding of receptor pharmacology and disease physiology. 25617829 0 21 theme receptor 53:60 arg1 expression 62:71 GPRC6A receptor expression 46:71 GPRC6A receptor expression 46:71 N-glycosylation and disulfide bonding affects GPRC6A receptor expression, function, and dimerization. 25617829 3 22 theme receptor 642:649 arg1 function 651:658 receptor function 642:658 receptor function 642:658 Herein, we show that the nutrient-sensing class C G protein-coupled receptor GPRC6A carries seven N-glycans and that one of these sites modulates surface expression whereas mutation of another site affects receptor function. 25617829 1 23 theme modifications 138:150 arg1 Investigation 102:114 Investigation 102:114 Investigation of post-translational modifications of receptor proteins 102:171 Investigation of post-translational modifications of receptor proteins is important for our understanding of receptor pharmacology and disease physiology. 25617829 4 24 link linked 707:712 arg1 dimers 714:719 covalently linked dimers 696:719 covalently linked dimers 696:719 GPRC6A has been speculated to form covalently linked dimers through cysteine disulfide linkage in the extracellular amino-terminal domain and here we show that GPRC6A indeed is a homodimer and that a disulfide bridge between the C131 residues is formed. 25617829 2 25 theme post-translational 286:303 arg1 modifications 305:317 post-translational modifications 286:317 post-translational modifications of class C G protein-coupled receptors 286:356 However, our knowledge about post-translational modifications of class C G protein-coupled receptors and how these modifications regulate expression and function is very limited. 25617829 1 26 theme receptor 155:162 arg1 proteins 164:171 receptor proteins 155:171 receptor proteins 155:171 Investigation of post-translational modifications of receptor proteins is important for our understanding of receptor pharmacology and disease physiology. 25617829 1 27 theme physiology 245:254 arg1 understanding 194:206 our understanding 190:206 our understanding of receptor pharmacology and disease physiology 190:254 Investigation of post-translational modifications of receptor proteins is important for our understanding of receptor pharmacology and disease physiology. 25617829 4 28 theme disulfide 861:869 arg1 bridge 871:876 a disulfide bridge 859:876 a disulfide bridge between the C131 residues 859:902 GPRC6A has been speculated to form covalently linked dimers through cysteine disulfide linkage in the extracellular amino-terminal domain and here we show that GPRC6A indeed is a homodimer and that a disulfide bridge between the C131 residues is formed. 25617829 1 29 theme proteins 164:171 arg1 modifications 138:150 post-translational modifications 119:150 post-translational modifications of receptor proteins 119:171 Investigation of post-translational modifications of receptor proteins is important for our understanding of receptor pharmacology and disease physiology. 25617829 3 30 theme sites 566:570 arg1 one 553:555 one 553:555 one 553:555 Herein, we show that the nutrient-sensing class C G protein-coupled receptor GPRC6A carries seven N-glycans and that one of these sites modulates surface expression whereas mutation of another site affects receptor function. 25617829 3 30 theme sites 566:570 arg1 sites 566:570 these sites 560:570 these sites 560:570 Herein, we show that the nutrient-sensing class C G protein-coupled receptor GPRC6A carries seven N-glycans and that one of these sites modulates surface expression whereas mutation of another site affects receptor function. 25327667 9 0 theme % 1278:1278 arg1 intensities 1250:1260 relative intensities 1241:1260 relative intensities of 0.52 and 0.28%, respectively 1241:1292 One of these sulfated/phosphorylated N-glycans, HexNAc5Hex4dHex1s/p1 was identified in both PSA and PSAH at relative intensities of 0.52 and 0.28%, respectively. 25327667 7 1 theme PSA-high 965:972 arg1 PSAH 1006:1009 PSAH 1006:1009 PSAH 1006:1009 There were 56 N-glycans associated with PSA, whereas 57 N-glycans were observed in the case of the PSA-high isoelectric point (pI) isoform (PSAH). 25327667 7 1 theme PSA-high 965:972 arg1 isoform 997:1003 the PSA-high isoelectric point (pI) isoform 961:1003 the PSA-high isoelectric point (pI) isoform (PSAH) 961:1010 There were 56 N-glycans associated with PSA, whereas 57 N-glycans were observed in the case of the PSA-high isoelectric point (pI) isoform (PSAH). 25327667 8 2 theme sulfated/phosphorylated 1019:1041 arg1 glycopeptides 1043:1055 Three sulfated/phosphorylated glycopeptides 1013:1055 Three sulfated/phosphorylated glycopeptides 1013:1055 Three sulfated/phosphorylated glycopeptides were detected, the identification of which was supported by tandem MS data. 25327667 11 3 theme Group 1462:1466 arg1 study 1475:1479 the 2012 ABRF Glycoprotein Research Group (gPRG) study 1426:1479 the 2012 ABRF Glycoprotein Research Group (gPRG) study 1426:1479 Because we were one of the laboratories participating in the 2012 ABRF Glycoprotein Research Group (gPRG) study, those results were compared to that presented in this study. 25327667 0 4 theme normal 79:84 arg1 points 107:112 normal and high isoelectric points 79:112 normal and high isoelectric points 79:112 Glycoproteomics: identifying the glycosylation of prostate specific antigen at normal and high isoelectric points by LC-MS/MS. 25327667 11 5 theme ABRF 1435:1438 arg1 study 1475:1479 the 2012 ABRF Glycoprotein Research Group (gPRG) study 1426:1479 the 2012 ABRF Glycoprotein Research Group (gPRG) study 1426:1479 Because we were one of the laboratories participating in the 2012 ABRF Glycoprotein Research Group (gPRG) study, those results were compared to that presented in this study. 25327667 4 6 theme in-depth 534:541 arg1 understanding 543:555 an in-depth understanding 531:555 an in-depth understanding of the biochemical characteristics of PSA (such as glycosylation) 531:621 To develop more specific and sensitive candidate biomarkers for prostate cancer, an in-depth understanding of the biochemical characteristics of PSA (such as glycosylation) is needed. 25327667 0 7 theme isoelectric 95:105 arg1 points 107:112 normal and high isoelectric points 79:112 normal and high isoelectric points 79:112 Glycoproteomics: identifying the glycosylation of prostate specific antigen at normal and high isoelectric points by LC-MS/MS. 25327667 4 8 theme specific 466:473 arg1 biomarkers 499:508 more specific and sensitive candidate biomarkers 461:508 more specific and sensitive candidate biomarkers for prostate cancer 461:528 To develop more specific and sensitive candidate biomarkers for prostate cancer, an in-depth understanding of the biochemical characteristics of PSA (such as glycosylation) is needed. 25327667 3 9 dep their 435:439 arg1 overlap 441:447 overlap 441:447 overlap 441:447 However, in the diagnostic gray zone, the PSA test does not clearly distinguish between benign prostate hypertrophy and prostate cancer due to their overlap. 25327667 11 10 theme Glycoprotein 1440:1451 arg1 study 1475:1479 the 2012 ABRF Glycoprotein Research Group (gPRG) study 1426:1479 the 2012 ABRF Glycoprotein Research Group (gPRG) study 1426:1479 Because we were one of the laboratories participating in the 2012 ABRF Glycoprotein Research Group (gPRG) study, those results were compared to that presented in this study. 25327667 8 11 theme which 1094:1098 arg1 identification 1076:1089 the identification 1072:1089 the identification 1072:1089 Three sulfated/phosphorylated glycopeptides were detected, the identification of which was supported by tandem MS data. 25327667 0 12 theme high 90:93 arg1 points 107:112 normal and high isoelectric points 79:112 normal and high isoelectric points 79:112 Glycoproteomics: identifying the glycosylation of prostate specific antigen at normal and high isoelectric points by LC-MS/MS. 25327667 9 13 theme relative 1241:1248 arg1 intensities 1250:1260 relative intensities 1241:1260 relative intensities of 0.52 and 0.28%, respectively 1241:1292 One of these sulfated/phosphorylated N-glycans, HexNAc5Hex4dHex1s/p1 was identified in both PSA and PSAH at relative intensities of 0.52 and 0.28%, respectively. 25327667 12 14 theme quantitative 1563:1574 arg1 results 1576:1582 Our qualitative and quantitative results 1543:1582 Our qualitative and quantitative results summarized here 1543:1598 Our qualitative and quantitative results summarized here were comparable to those that were summarized in the interlaboratory study. 25327667 3 15 theme diagnostic 308:317 arg1 zone 324:327 the diagnostic gray zone 304:327 the diagnostic gray zone 304:327 However, in the diagnostic gray zone, the PSA test does not clearly distinguish between benign prostate hypertrophy and prostate cancer due to their overlap. 25327667 6 16 theme PSA 837:839 arg1 isoforms 841:848 two PSA isoforms 833:848 two PSA isoforms using LC-MS/MS 833:863 Here, we report the comprehensive identification and quantitation of N-glycans from two PSA isoforms using LC-MS/MS. 25327667 11 17 theme gPRG 1469:1472 arg1 study 1475:1479 the 2012 ABRF Glycoprotein Research Group (gPRG) study 1426:1479 the 2012 ABRF Glycoprotein Research Group (gPRG) study 1426:1479 Because we were one of the laboratories participating in the 2012 ABRF Glycoprotein Research Group (gPRG) study, those results were compared to that presented in this study. 25327667 3 18 theme gray 319:322 arg1 zone 324:327 the diagnostic gray zone 304:327 the diagnostic gray zone 304:327 However, in the diagnostic gray zone, the PSA test does not clearly distinguish between benign prostate hypertrophy and prostate cancer due to their overlap. 25327667 11 19 theme Research 1453:1460 arg1 study 1475:1479 the 2012 ABRF Glycoprotein Research Group (gPRG) study 1426:1479 the 2012 ABRF Glycoprotein Research Group (gPRG) study 1426:1479 Because we were one of the laboratories participating in the 2012 ABRF Glycoprotein Research Group (gPRG) study, those results were compared to that presented in this study. 25327667 6 20 from isoforms 841:848 arg1 quantitation 802:813 quantitation 802:813 quantitation 802:813 Here, we report the comprehensive identification and quantitation of N-glycans from two PSA isoforms using LC-MS/MS. 25327667 6 20 from isoforms 841:848 arg1 identification 783:796 identification 783:796 identification 783:796 Here, we report the comprehensive identification and quantitation of N-glycans from two PSA isoforms using LC-MS/MS. 25327667 8 21 theme tandem 1117:1122 arg1 data 1127:1130 tandem MS data 1117:1130 tandem MS data 1117:1130 Three sulfated/phosphorylated glycopeptides were detected, the identification of which was supported by tandem MS data. 25327667 9 22 theme 0.52 1265:1268 arg1 intensities 1250:1260 relative intensities 1241:1260 relative intensities of 0.52 and 0.28%, respectively 1241:1292 One of these sulfated/phosphorylated N-glycans, HexNAc5Hex4dHex1s/p1 was identified in both PSA and PSAH at relative intensities of 0.52 and 0.28%, respectively. 25327667 12 23 theme interlaboratory 1653:1667 arg1 study 1669:1673 the interlaboratory study 1649:1673 the interlaboratory study 1649:1673 Our qualitative and quantitative results summarized here were comparable to those that were summarized in the interlaboratory study. 25327667 3 24 theme benign 380:385 arg1 hypertrophy 396:406 benign prostate hypertrophy 380:406 benign prostate hypertrophy 380:406 However, in the diagnostic gray zone, the PSA test does not clearly distinguish between benign prostate hypertrophy and prostate cancer due to their overlap. 25327667 8 25 dep detected 1062:1069 arg1 supported 1104:1112 supported 1104:1112 was supported by tandem MS data 1100:1130 Three sulfated/phosphorylated glycopeptides were detected, the identification of which was supported by tandem MS data. 25327667 12 26 theme qualitative 1547:1557 arg1 results 1576:1582 Our qualitative and quantitative results 1543:1582 Our qualitative and quantitative results summarized here 1543:1598 Our qualitative and quantitative results summarized here were comparable to those that were summarized in the interlaboratory study. 25327667 3 27 theme prostate 387:394 arg1 hypertrophy 396:406 benign prostate hypertrophy 380:406 benign prostate hypertrophy 380:406 However, in the diagnostic gray zone, the PSA test does not clearly distinguish between benign prostate hypertrophy and prostate cancer due to their overlap. 25327667 4 28 theme prostate 514:521 arg1 cancer 523:528 prostate cancer 514:528 prostate cancer 514:528 To develop more specific and sensitive candidate biomarkers for prostate cancer, an in-depth understanding of the biochemical characteristics of PSA (such as glycosylation) is needed. 25327667 5 29 theme glycosylation 651:663 arg1 site 665:668 a single glycosylation site 642:668 a single glycosylation site at Asn69 642:677 PSA has a single glycosylation site at Asn69, with glycans constituting approximately 8% of the protein by weight. 25327667 2 30 theme prostate 275:282 arg1 cancer 284:289 prostate cancer 275:289 prostate cancer 275:289 PSA testing has been widely used to detect and screen prostate cancer. 25327667 11 31 theme laboratories 1396:1407 arg1 one 1385:1387 one 1385:1387 one 1385:1387 Because we were one of the laboratories participating in the 2012 ABRF Glycoprotein Research Group (gPRG) study, those results were compared to that presented in this study. 25327667 11 31 theme laboratories 1396:1407 arg1 laboratories 1396:1407 the laboratories 1392:1407 the laboratories participating in the 2012 ABRF Glycoprotein Research Group (gPRG) study 1392:1479 Because we were one of the laboratories participating in the 2012 ABRF Glycoprotein Research Group (gPRG) study, those results were compared to that presented in this study. 25327667 3 32 theme PSA 334:336 arg1 test 338:341 the PSA test 330:341 the PSA test 330:341 However, in the diagnostic gray zone, the PSA test does not clearly distinguish between benign prostate hypertrophy and prostate cancer due to their overlap. 25327667 6 33 dep identification 783:796 arg1 the 765:767 the 765:767 the 765:767 Here, we report the comprehensive identification and quantitation of N-glycans from two PSA isoforms using LC-MS/MS. 25327667 7 34 theme isoform 997:1003 arg1 case 953:956 the case 949:956 the case of the PSA-high isoelectric point (pI) isoform (PSAH) 949:1010 There were 56 N-glycans associated with PSA, whereas 57 N-glycans were observed in the case of the PSA-high isoelectric point (pI) isoform (PSAH). 25327667 6 35 theme N-glycans 818:826 arg1 quantitation 802:813 quantitation 802:813 quantitation 802:813 Here, we report the comprehensive identification and quantitation of N-glycans from two PSA isoforms using LC-MS/MS. 25327667 6 35 theme N-glycans 818:826 arg1 identification 783:796 identification 783:796 identification 783:796 Here, we report the comprehensive identification and quantitation of N-glycans from two PSA isoforms using LC-MS/MS. 25327667 8 36 gly glycopeptides 1043:1055 arg2 glycopeptides 1043:1055 Three sulfated/phosphorylated glycopeptides 1013:1055 Three sulfated/phosphorylated glycopeptides 1013:1055 Three sulfated/phosphorylated glycopeptides were detected, the identification of which was supported by tandem MS data. 25327667 9 37 theme N-glycans 1170:1178 arg1 One 1133:1135 One 1133:1135 One 1133:1135 One of these sulfated/phosphorylated N-glycans, HexNAc5Hex4dHex1s/p1 was identified in both PSA and PSAH at relative intensities of 0.52 and 0.28%, respectively. 25327667 9 37 theme N-glycans 1170:1178 arg1 HexNAc5Hex4dHex1s/p1 1181:1200 HexNAc5Hex4dHex1s/p1 1181:1200 HexNAc5Hex4dHex1s/p1 1181:1200 One of these sulfated/phosphorylated N-glycans, HexNAc5Hex4dHex1s/p1 was identified in both PSA and PSAH at relative intensities of 0.52 and 0.28%, respectively. 25327667 9 37 theme N-glycans 1170:1178 arg1 N-glycans 1170:1178 these sulfated/phosphorylated N-glycans 1140:1178 these sulfated/phosphorylated N-glycans 1140:1178 One of these sulfated/phosphorylated N-glycans, HexNAc5Hex4dHex1s/p1 was identified in both PSA and PSAH at relative intensities of 0.52 and 0.28%, respectively. 25327667 2 38 theme PSA 221:223 arg1 testing 225:231 PSA testing 221:231 PSA testing 221:231 PSA testing has been widely used to detect and screen prostate cancer. 25327667 3 39 theme prostate 412:419 arg1 cancer 421:426 prostate cancer 412:426 prostate cancer 412:426 However, in the diagnostic gray zone, the PSA test does not clearly distinguish between benign prostate hypertrophy and prostate cancer due to their overlap. 25327667 5 40 theme protein 730:736 arg1 % 721:721 approximately 8% 706:721 approximately 8% of the protein by weight 706:746 PSA has a single glycosylation site at Asn69, with glycans constituting approximately 8% of the protein by weight. 25327667 5 40 theme protein 730:736 arg1 protein 730:736 the protein 726:736 the protein 726:736 PSA has a single glycosylation site at Asn69, with glycans constituting approximately 8% of the protein by weight. 25327667 4 41 theme candidate 489:497 arg1 biomarkers 499:508 more specific and sensitive candidate biomarkers 461:508 more specific and sensitive candidate biomarkers for prostate cancer 461:528 To develop more specific and sensitive candidate biomarkers for prostate cancer, an in-depth understanding of the biochemical characteristics of PSA (such as glycosylation) is needed. 25327667 5 42 from Asn69 673:677 arg1 site 665:668 a single glycosylation site 642:668 a single glycosylation site at Asn69 642:677 PSA has a single glycosylation site at Asn69, with glycans constituting approximately 8% of the protein by weight. 25327667 1 43 theme diagnose 195:202 arg1 cancer 213:218 diagnose prostate cancer 195:218 diagnose prostate cancer 195:218 Prostate specific antigen (PSA) is currently used as a biomarker to diagnose prostate cancer. 25327667 0 44 theme specific 59:66 arg1 antigen 68:74 prostate specific antigen 50:74 prostate specific antigen 50:74 Glycoproteomics: identifying the glycosylation of prostate specific antigen at normal and high isoelectric points by LC-MS/MS. 25327667 4 45 theme sensitive 479:487 arg1 biomarkers 499:508 more specific and sensitive candidate biomarkers 461:508 more specific and sensitive candidate biomarkers for prostate cancer 461:528 To develop more specific and sensitive candidate biomarkers for prostate cancer, an in-depth understanding of the biochemical characteristics of PSA (such as glycosylation) is needed. 25327667 7 46 theme isoelectric 974:984 arg1 PSAH 1006:1009 PSAH 1006:1009 PSAH 1006:1009 There were 56 N-glycans associated with PSA, whereas 57 N-glycans were observed in the case of the PSA-high isoelectric point (pI) isoform (PSAH). 25327667 7 46 theme isoelectric 974:984 arg1 isoform 997:1003 the PSA-high isoelectric point (pI) isoform 961:1003 the PSA-high isoelectric point (pI) isoform (PSAH) 961:1010 There were 56 N-glycans associated with PSA, whereas 57 N-glycans were observed in the case of the PSA-high isoelectric point (pI) isoform (PSAH). 25327667 7 47 theme pI 993:994 arg1 PSAH 1006:1009 PSAH 1006:1009 PSAH 1006:1009 There were 56 N-glycans associated with PSA, whereas 57 N-glycans were observed in the case of the PSA-high isoelectric point (pI) isoform (PSAH). 25327667 7 47 theme pI 993:994 arg1 isoform 997:1003 the PSA-high isoelectric point (pI) isoform 961:1003 the PSA-high isoelectric point (pI) isoform (PSAH) 961:1010 There were 56 N-glycans associated with PSA, whereas 57 N-glycans were observed in the case of the PSA-high isoelectric point (pI) isoform (PSAH). 25327667 0 48 theme prostate 50:57 arg1 antigen 68:74 prostate specific antigen 50:74 prostate specific antigen 50:74 Glycoproteomics: identifying the glycosylation of prostate specific antigen at normal and high isoelectric points by LC-MS/MS. 25327667 5 49 contain has 638:640 arg1 PSA 634:636 PSA 634:636 PSA 634:636 PSA has a single glycosylation site at Asn69, with glycans constituting approximately 8% of the protein by weight. 25327667 5 49 contain has 638:640 arg2 site 665:668 a single glycosylation site 642:668 a single glycosylation site at Asn69 642:677 PSA has a single glycosylation site at Asn69, with glycans constituting approximately 8% of the protein by weight. 25327667 7 50 theme point 986:990 arg1 PSAH 1006:1009 PSAH 1006:1009 PSAH 1006:1009 There were 56 N-glycans associated with PSA, whereas 57 N-glycans were observed in the case of the PSA-high isoelectric point (pI) isoform (PSAH). 25327667 7 50 theme point 986:990 arg1 isoform 997:1003 the PSA-high isoelectric point (pI) isoform 961:1003 the PSA-high isoelectric point (pI) isoform (PSAH) 961:1010 There were 56 N-glycans associated with PSA, whereas 57 N-glycans were observed in the case of the PSA-high isoelectric point (pI) isoform (PSAH). 25327667 6 51 theme comprehensive 769:781 arg1 identification 783:796 identification 783:796 identification 783:796 Here, we report the comprehensive identification and quantitation of N-glycans from two PSA isoforms using LC-MS/MS. 25327667 5 52 gly glycosylation 651:663 arg2 Asn69 673:677 Asn69 673:677 Asn69 673:677 PSA has a single glycosylation site at Asn69, with glycans constituting approximately 8% of the protein by weight. 25327667 5 52 gly glycosylation 651:663 arg2 site 665:668 a single glycosylation site 642:668 a single glycosylation site at Asn69 642:677 PSA has a single glycosylation site at Asn69, with glycans constituting approximately 8% of the protein by weight. 25327667 0 53 from points 107:112 arg1 glycosylation 33:45 the glycosylation 29:45 the glycosylation of prostate specific antigen at normal and high isoelectric points 29:112 Glycoproteomics: identifying the glycosylation of prostate specific antigen at normal and high isoelectric points by LC-MS/MS. 25327667 0 54 gly glycosylation 33:45 arg1 antigen 68:74 prostate specific antigen 50:74 prostate specific antigen 50:74 Glycoproteomics: identifying the glycosylation of prostate specific antigen at normal and high isoelectric points by LC-MS/MS. 25327667 0 54 gly glycosylation 33:45 arg2 points 107:112 normal and high isoelectric points 79:112 normal and high isoelectric points 79:112 Glycoproteomics: identifying the glycosylation of prostate specific antigen at normal and high isoelectric points by LC-MS/MS. 25327667 0 54 gly glycosylation 33:45 arg1 points 107:112 normal and high isoelectric points 79:112 normal and high isoelectric points 79:112 Glycoproteomics: identifying the glycosylation of prostate specific antigen at normal and high isoelectric points by LC-MS/MS. 25327667 1 55 theme Prostate 127:134 arg1 biomarker 182:190 a biomarker 180:190 a biomarker to diagnose prostate cancer 180:218 Prostate specific antigen (PSA) is currently used as a biomarker to diagnose prostate cancer. 25327667 1 55 theme Prostate 127:134 arg1 PSA 154:156 PSA 154:156 PSA 154:156 Prostate specific antigen (PSA) is currently used as a biomarker to diagnose prostate cancer. 25327667 1 55 theme Prostate 127:134 arg1 antigen 145:151 Prostate specific antigen 127:151 Prostate specific antigen (PSA) 127:157 Prostate specific antigen (PSA) is currently used as a biomarker to diagnose prostate cancer. 25327667 11 56 theme 2012 1430:1433 arg1 study 1475:1479 the 2012 ABRF Glycoprotein Research Group (gPRG) study 1426:1479 the 2012 ABRF Glycoprotein Research Group (gPRG) study 1426:1479 Because we were one of the laboratories participating in the 2012 ABRF Glycoprotein Research Group (gPRG) study, those results were compared to that presented in this study. 25327667 1 57 theme prostate 204:211 arg1 cancer 213:218 diagnose prostate cancer 195:218 diagnose prostate cancer 195:218 Prostate specific antigen (PSA) is currently used as a biomarker to diagnose prostate cancer. 25327667 5 58 theme single 644:649 arg1 site 665:668 a single glycosylation site 642:668 a single glycosylation site at Asn69 642:677 PSA has a single glycosylation site at Asn69, with glycans constituting approximately 8% of the protein by weight. 25327667 4 59 dep characteristics 576:590 arg1 such 600:603 such 600:603 such 600:603 To develop more specific and sensitive candidate biomarkers for prostate cancer, an in-depth understanding of the biochemical characteristics of PSA (such as glycosylation) is needed. 25327667 1 60 used used 172:175 arg2 biomarker 182:190 a biomarker 180:190 a biomarker to diagnose prostate cancer 180:218 Prostate specific antigen (PSA) is currently used as a biomarker to diagnose prostate cancer. 25327667 1 60 used used 172:175 arg2 PSA 154:156 PSA 154:156 PSA 154:156 Prostate specific antigen (PSA) is currently used as a biomarker to diagnose prostate cancer. 25327667 1 60 used used 172:175 arg2 antigen 145:151 Prostate specific antigen 127:151 Prostate specific antigen (PSA) 127:157 Prostate specific antigen (PSA) is currently used as a biomarker to diagnose prostate cancer. 25327667 1 61 theme specific 136:143 arg1 biomarker 182:190 a biomarker 180:190 a biomarker to diagnose prostate cancer 180:218 Prostate specific antigen (PSA) is currently used as a biomarker to diagnose prostate cancer. 25327667 1 61 theme specific 136:143 arg1 PSA 154:156 PSA 154:156 PSA 154:156 Prostate specific antigen (PSA) is currently used as a biomarker to diagnose prostate cancer. 25327667 1 61 theme specific 136:143 arg1 antigen 145:151 Prostate specific antigen 127:151 Prostate specific antigen (PSA) 127:157 Prostate specific antigen (PSA) is currently used as a biomarker to diagnose prostate cancer. 25327667 4 62 theme biochemical 564:574 arg1 characteristics 576:590 the biochemical characteristics 560:590 the biochemical characteristics of PSA (such as glycosylation) 560:621 To develop more specific and sensitive candidate biomarkers for prostate cancer, an in-depth understanding of the biochemical characteristics of PSA (such as glycosylation) is needed. 25327667 7 63 located observed 937:944 arg1 case 953:956 the case 949:956 the case of the PSA-high isoelectric point (pI) isoform (PSAH) 949:1010 There were 56 N-glycans associated with PSA, whereas 57 N-glycans were observed in the case of the PSA-high isoelectric point (pI) isoform (PSAH). 25327667 7 63 located observed 937:944 arg2 N-glycans 922:930 57 N-glycans 919:930 57 N-glycans 919:930 There were 56 N-glycans associated with PSA, whereas 57 N-glycans were observed in the case of the PSA-high isoelectric point (pI) isoform (PSAH). 25327667 9 64 theme sulfated/phosphorylated 1146:1168 arg1 N-glycans 1170:1178 these sulfated/phosphorylated N-glycans 1140:1178 these sulfated/phosphorylated N-glycans 1140:1178 One of these sulfated/phosphorylated N-glycans, HexNAc5Hex4dHex1s/p1 was identified in both PSA and PSAH at relative intensities of 0.52 and 0.28%, respectively. 25327667 7 65 dep were 872:875 arg1 whereas 911:917 whereas 911:917 whereas 911:917 There were 56 N-glycans associated with PSA, whereas 57 N-glycans were observed in the case of the PSA-high isoelectric point (pI) isoform (PSAH). 25327667 4 66 theme PSA 595:597 arg1 characteristics 576:590 the biochemical characteristics 560:590 the biochemical characteristics of PSA (such as glycosylation) 560:621 To develop more specific and sensitive candidate biomarkers for prostate cancer, an in-depth understanding of the biochemical characteristics of PSA (such as glycosylation) is needed. 25327667 0 67 theme antigen 68:74 arg1 glycosylation 33:45 the glycosylation 29:45 the glycosylation of prostate specific antigen at normal and high isoelectric points 29:112 Glycoproteomics: identifying the glycosylation of prostate specific antigen at normal and high isoelectric points by LC-MS/MS. 25327667 8 68 theme MS 1124:1125 arg1 data 1127:1130 tandem MS data 1117:1130 tandem MS data 1117:1130 Three sulfated/phosphorylated glycopeptides were detected, the identification of which was supported by tandem MS data. 25327667 4 69 theme characteristics 576:590 arg1 understanding 543:555 an in-depth understanding 531:555 an in-depth understanding of the biochemical characteristics of PSA (such as glycosylation) 531:621 To develop more specific and sensitive candidate biomarkers for prostate cancer, an in-depth understanding of the biochemical characteristics of PSA (such as glycosylation) is needed. 25327667 2 70 used used 249:252 arg2 testing 225:231 PSA testing 221:231 PSA testing 221:231 PSA testing has been widely used to detect and screen prostate cancer. 24269691 0 0 theme cell 98:101 arg1 levels 122:127 cell surface expression levels 98:127 cell surface expression levels 98:127 Allelic variation of killer cell immunoglobulin-like receptor 2DS5 impacts glycosylation altering cell surface expression levels. 24269691 4 1 theme products 457:464 arg1 electrophoresis 426:440 Gel electrophoresis 422:440 Gel electrophoresis of all allelic products 422:464 Gel electrophoresis of all allelic products showed two isoforms which differ in the extent of maturation of N-linked glycosylation. 24269691 4 2 theme glycosylation 539:551 arg1 maturation 516:525 maturation 516:525 maturation of N-linked glycosylation 516:551 Gel electrophoresis of all allelic products showed two isoforms which differ in the extent of maturation of N-linked glycosylation. 24269691 6 3 from 157 729:731 arg1 variation 699:707 polymorphic variation 687:707 polymorphic variation at residues 123 and 157 687:731 Site-directed mutagenesis was used to identify polymorphic variation at residues 123 and 157 as key in altering glycosylation and levels of surface expression. 24269691 5 4 theme allelic 622:628 arg1 products 630:637 the allelic products 618:637 the allelic products 618:637 These isoforms differed in intensity and molecular weight among the allelic products. 24269691 4 5 theme N-linked 530:537 arg1 glycosylation 539:551 N-linked glycosylation 530:551 N-linked glycosylation 530:551 Gel electrophoresis of all allelic products showed two isoforms which differ in the extent of maturation of N-linked glycosylation. 24269691 0 6 theme expression 111:120 arg1 levels 122:127 cell surface expression levels 98:127 cell surface expression levels 98:127 Allelic variation of killer cell immunoglobulin-like receptor 2DS5 impacts glycosylation altering cell surface expression levels. 24269691 6 7 theme expression 788:797 arg1 levels 770:775 levels 770:775 levels of surface expression 770:797 Site-directed mutagenesis was used to identify polymorphic variation at residues 123 and 157 as key in altering glycosylation and levels of surface expression. 24269691 6 7 theme expression 788:797 arg1 glycosylation 752:764 glycosylation 752:764 glycosylation 752:764 Site-directed mutagenesis was used to identify polymorphic variation at residues 123 and 157 as key in altering glycosylation and levels of surface expression. 24269691 3 8 theme varying 359:365 arg1 levels 367:372 varying levels 359:372 varying levels 359:372 The proteins encoded by these alleles (KIR2DS5*002-*009) are expressed at varying levels on the surface of NKL and Jurkat transfectants. 24269691 0 9 theme surface 103:109 arg1 levels 122:127 cell surface expression levels 98:127 cell surface expression levels 98:127 Allelic variation of killer cell immunoglobulin-like receptor 2DS5 impacts glycosylation altering cell surface expression levels. 24269691 6 10 theme surface 780:786 arg1 expression 788:797 surface expression 780:797 surface expression 780:797 Site-directed mutagenesis was used to identify polymorphic variation at residues 123 and 157 as key in altering glycosylation and levels of surface expression. 24269691 3 11 theme * 331:331 arg1 * 336:336 KIR2DS5*002-*009 324:339 KIR2DS5*002-*009 324:339 The proteins encoded by these alleles (KIR2DS5*002-*009) are expressed at varying levels on the surface of NKL and Jurkat transfectants. 24269691 3 11 theme * 331:331 arg1 alleles 315:321 these alleles 309:321 these alleles (KIR2DS5*002-*009) 309:340 The proteins encoded by these alleles (KIR2DS5*002-*009) are expressed at varying levels on the surface of NKL and Jurkat transfectants. 24269691 6 12 theme polymorphic 687:697 arg1 variation 699:707 polymorphic variation 687:707 polymorphic variation at residues 123 and 157 687:731 Site-directed mutagenesis was used to identify polymorphic variation at residues 123 and 157 as key in altering glycosylation and levels of surface expression. 24269691 3 13 theme NKL 392:394 arg1 surface 381:387 the surface 377:387 the surface of NKL and Jurkat transfectants 377:419 The proteins encoded by these alleles (KIR2DS5*002-*009) are expressed at varying levels on the surface of NKL and Jurkat transfectants. 24269691 3 14 theme 002- 332:335 arg1 * 336:336 KIR2DS5*002-*009 324:339 KIR2DS5*002-*009 324:339 The proteins encoded by these alleles (KIR2DS5*002-*009) are expressed at varying levels on the surface of NKL and Jurkat transfectants. 24269691 3 14 theme 002- 332:335 arg1 alleles 315:321 these alleles 309:321 these alleles (KIR2DS5*002-*009) 309:340 The proteins encoded by these alleles (KIR2DS5*002-*009) are expressed at varying levels on the surface of NKL and Jurkat transfectants. 24269691 4 15 theme allelic 449:455 arg1 products 457:464 all allelic products 445:464 all allelic products 445:464 Gel electrophoresis of all allelic products showed two isoforms which differ in the extent of maturation of N-linked glycosylation. 24269691 5 16 theme molecular 595:603 arg1 weight 605:610 molecular weight 595:610 molecular weight 595:610 These isoforms differed in intensity and molecular weight among the allelic products. 24269691 6 17 used used 670:673 arg2 mutagenesis 654:664 Site-directed mutagenesis 640:664 Site-directed mutagenesis 640:664 Site-directed mutagenesis was used to identify polymorphic variation at residues 123 and 157 as key in altering glycosylation and levels of surface expression. 24269691 6 18 gly glycosylation 752:764 arg1 expression 788:797 surface expression 780:797 surface expression 780:797 Site-directed mutagenesis was used to identify polymorphic variation at residues 123 and 157 as key in altering glycosylation and levels of surface expression. 24269691 0 19 theme Allelic 0:6 arg1 variation 8:16 Allelic variation 0:16 Allelic variation of killer cell immunoglobulin-like receptor 2DS5 0:65 Allelic variation of killer cell immunoglobulin-like receptor 2DS5 impacts glycosylation altering cell surface expression levels. 24269691 0 20 theme killer 21:26 arg1 2DS5 62:65 killer cell immunoglobulin-like receptor 2DS5 21:65 killer cell immunoglobulin-like receptor 2DS5 21:65 Allelic variation of killer cell immunoglobulin-like receptor 2DS5 impacts glycosylation altering cell surface expression levels. 24269691 6 21 from residues 712:719 arg1 variation 699:707 polymorphic variation 687:707 polymorphic variation at residues 123 and 157 687:731 Site-directed mutagenesis was used to identify polymorphic variation at residues 123 and 157 as key in altering glycosylation and levels of surface expression. 24269691 0 22 theme immunoglobulin-like 33:51 arg1 2DS5 62:65 killer cell immunoglobulin-like receptor 2DS5 21:65 killer cell immunoglobulin-like receptor 2DS5 21:65 Allelic variation of killer cell immunoglobulin-like receptor 2DS5 impacts glycosylation altering cell surface expression levels. 24269691 4 23 theme maturation 516:525 arg1 extent 506:511 the extent 502:511 the extent of maturation of N-linked glycosylation 502:551 Gel electrophoresis of all allelic products showed two isoforms which differ in the extent of maturation of N-linked glycosylation. 24269691 6 24 theme Site-directed 640:652 arg1 mutagenesis 654:664 Site-directed mutagenesis 640:664 Site-directed mutagenesis 640:664 Site-directed mutagenesis was used to identify polymorphic variation at residues 123 and 157 as key in altering glycosylation and levels of surface expression. 24269691 3 25 theme Jurkat 400:405 arg1 transfectants 407:419 Jurkat transfectants 400:419 Jurkat transfectants 400:419 The proteins encoded by these alleles (KIR2DS5*002-*009) are expressed at varying levels on the surface of NKL and Jurkat transfectants. 24269691 0 26 theme cell 28:31 arg1 2DS5 62:65 killer cell immunoglobulin-like receptor 2DS5 21:65 killer cell immunoglobulin-like receptor 2DS5 21:65 Allelic variation of killer cell immunoglobulin-like receptor 2DS5 impacts glycosylation altering cell surface expression levels. 24269691 4 27 theme Gel 422:424 arg1 electrophoresis 426:440 Gel electrophoresis 422:440 Gel electrophoresis of all allelic products 422:464 Gel electrophoresis of all allelic products showed two isoforms which differ in the extent of maturation of N-linked glycosylation. 24269691 3 28 theme transfectants 407:419 arg1 surface 381:387 the surface 377:387 the surface of NKL and Jurkat transfectants 377:419 The proteins encoded by these alleles (KIR2DS5*002-*009) are expressed at varying levels on the surface of NKL and Jurkat transfectants. 24269691 0 29 theme 2DS5 62:65 arg1 variation 8:16 Allelic variation 0:16 Allelic variation of killer cell immunoglobulin-like receptor 2DS5 0:65 Allelic variation of killer cell immunoglobulin-like receptor 2DS5 impacts glycosylation altering cell surface expression levels. 24269691 1 30 theme Natural 130:136 arg1 gene 171:174 Natural killer cell stimulatory receptor gene 130:174 Natural killer cell stimulatory receptor gene 130:174 Natural killer cell stimulatory receptor gene, KIR2DS5, is polymorphic. 24269691 1 30 theme Natural 130:136 arg1 KIR2DS5 177:183 KIR2DS5 177:183 KIR2DS5 177:183 Natural killer cell stimulatory receptor gene, KIR2DS5, is polymorphic. 24269691 0 31 theme receptor 53:60 arg1 2DS5 62:65 killer cell immunoglobulin-like receptor 2DS5 21:65 killer cell immunoglobulin-like receptor 2DS5 21:65 Allelic variation of killer cell immunoglobulin-like receptor 2DS5 impacts glycosylation altering cell surface expression levels. 24269691 1 32 theme killer 138:143 arg1 gene 171:174 Natural killer cell stimulatory receptor gene 130:174 Natural killer cell stimulatory receptor gene 130:174 Natural killer cell stimulatory receptor gene, KIR2DS5, is polymorphic. 24269691 1 32 theme killer 138:143 arg1 KIR2DS5 177:183 KIR2DS5 177:183 KIR2DS5 177:183 Natural killer cell stimulatory receptor gene, KIR2DS5, is polymorphic. 24269691 1 33 theme cell 145:148 arg1 gene 171:174 Natural killer cell stimulatory receptor gene 130:174 Natural killer cell stimulatory receptor gene 130:174 Natural killer cell stimulatory receptor gene, KIR2DS5, is polymorphic. 24269691 1 33 theme cell 145:148 arg1 KIR2DS5 177:183 KIR2DS5 177:183 KIR2DS5 177:183 Natural killer cell stimulatory receptor gene, KIR2DS5, is polymorphic. 24269691 2 34 theme KIR2DS5 208:214 arg1 * 215:215 KIR2DS5*002 208:218 KIR2DS5*002 208:218 While KIR2DS5*002 is most frequently observed, other alleles have also been found. 24269691 1 35 theme stimulatory 150:160 arg1 gene 171:174 Natural killer cell stimulatory receptor gene 130:174 Natural killer cell stimulatory receptor gene 130:174 Natural killer cell stimulatory receptor gene, KIR2DS5, is polymorphic. 24269691 1 35 theme stimulatory 150:160 arg1 KIR2DS5 177:183 KIR2DS5 177:183 KIR2DS5 177:183 Natural killer cell stimulatory receptor gene, KIR2DS5, is polymorphic. 24269691 4 36 link N-linked 530:537 arg1 glycosylation 539:551 N-linked glycosylation 530:551 N-linked glycosylation 530:551 Gel electrophoresis of all allelic products showed two isoforms which differ in the extent of maturation of N-linked glycosylation. 24269691 2 37 theme other 249:253 arg1 alleles 255:261 other alleles 249:261 other alleles 249:261 While KIR2DS5*002 is most frequently observed, other alleles have also been found. 24269691 1 38 theme receptor 162:169 arg1 gene 171:174 Natural killer cell stimulatory receptor gene 130:174 Natural killer cell stimulatory receptor gene 130:174 Natural killer cell stimulatory receptor gene, KIR2DS5, is polymorphic. 24269691 1 38 theme receptor 162:169 arg1 KIR2DS5 177:183 KIR2DS5 177:183 KIR2DS5 177:183 Natural killer cell stimulatory receptor gene, KIR2DS5, is polymorphic. 24269691 3 39 theme KIR2DS5 324:330 arg1 * 336:336 KIR2DS5*002-*009 324:339 KIR2DS5*002-*009 324:339 The proteins encoded by these alleles (KIR2DS5*002-*009) are expressed at varying levels on the surface of NKL and Jurkat transfectants. 24269691 3 39 theme KIR2DS5 324:330 arg1 alleles 315:321 these alleles 309:321 these alleles (KIR2DS5*002-*009) 309:340 The proteins encoded by these alleles (KIR2DS5*002-*009) are expressed at varying levels on the surface of NKL and Jurkat transfectants. 26894747 5 0 theme bio-orthogonal 726:739 arg1 groups 741:746 bio-orthogonal groups 726:746 bio-orthogonal groups 726:746 The introduction of bio-orthogonal groups into proteins accelerates research in the robust visualization, identification, and quantification of proteins. 26894747 4 1 theme surface 659:665 arg1 glycoproteins 667:679 surface glycoproteins 659:679 surface glycoproteins prior to MS measurement 659:703 Currently mass spectrometry (MS)-based proteomics provides the possibility to analyze the N-glycoproteome, but effective separation and enrichment methods are required for the analysis of surface glycoproteins prior to MS measurement. 26894747 7 2 theme greatest 1242:1249 arg1 number 1251:1256 the greatest number 1238:1256 the greatest number of glycoproteins and glycosylation sites in biological duplicate experiments 1238:1333 Comparison of three sugar analogs, N-azidoacetylgalactosamine (GalNAz), N-azidoacetylglucosamine (GlcNAz), and N-azidoacetylmannosamine (ManNAz), showed that metabolic labeling with GalNAz resulted in the greatest number of glycoproteins and glycosylation sites in biological duplicate experiments. 26894747 6 3 theme sugar 909:913 arg1 analogs 915:921 different sugar analogs 899:921 different sugar analogs in the analysis of cell-surface N-glycoproteins 899:969 Here we have comprehensively evaluated different sugar analogs in the analysis of cell-surface N-glycoproteins by combining copper-free click chemistry and MS-based proteomics. 26894747 10 4 from sites 1830:1834 arg1 proteins 1839:1846 proteins 1839:1846 proteins that participate in the Alzheimer's disease pathway 1839:1898 Several glycosylation sites in proteins that participate in the Alzheimer's disease pathway were down-regulated. 26894747 1 5 theme many 189:192 arg1 processes 205:213 many biological processes 189:213 many biological processes 189:213 The frequent modification of cell-surface proteins by N-linked glycans is known to be correlated with many biological processes. 26894747 6 6 theme click 996:1000 arg1 proteomics 1025:1034 copper-free click chemistry and MS-based proteomics 984:1034 copper-free click chemistry and MS-based proteomics 984:1034 Here we have comprehensively evaluated different sugar analogs in the analysis of cell-surface N-glycoproteins by combining copper-free click chemistry and MS-based proteomics. 26894747 8 7 theme HepG2 1413:1417 arg1 cells 1425:1429 statin-treated HepG2 liver cells 1398:1429 statin-treated HepG2 liver cells 1398:1429 GalNAz was then employed for the quantification experiment in statin-treated HepG2 liver cells, and 280 unique N-glycosylated sites were quantified from 168 surface proteins. 26894747 10 8 theme Several 1808:1814 arg1 sites 1830:1834 Several glycosylation sites 1808:1834 Several glycosylation sites in proteins that participate in the Alzheimer's disease pathway 1808:1898 Several glycosylation sites in proteins that participate in the Alzheimer's disease pathway were down-regulated. 26894747 5 9 theme robust 790:795 arg1 visualization 797:809 robust visualization 790:809 robust visualization 790:809 The introduction of bio-orthogonal groups into proteins accelerates research in the robust visualization, identification, and quantification of proteins. 26894747 9 10 theme untreated 1657:1665 arg1 cells 1667:1671 untreated cells 1657:1671 untreated cells 1657:1671 The quantification results demonstrated that many glycosylation sites on surface proteins were down-regulated in statin-treated cells compared to untreated cells because statin prevents the synthesis of dolichol, which is essential for the formation of dolichol-linked precursor oligosaccharides. 26894747 8 11 theme quantification 1369:1382 arg1 experiment 1384:1393 the quantification experiment 1365:1393 the quantification experiment in statin-treated HepG2 liver cells 1365:1429 GalNAz was then employed for the quantification experiment in statin-treated HepG2 liver cells, and 280 unique N-glycosylated sites were quantified from 168 surface proteins. 26894747 8 12 theme unique 1440:1445 arg1 sites 1462:1466 280 unique N-glycosylated sites 1436:1466 280 unique N-glycosylated sites 1436:1466 GalNAz was then employed for the quantification experiment in statin-treated HepG2 liver cells, and 280 unique N-glycosylated sites were quantified from 168 surface proteins. 26894747 2 13 theme surface 242:248 arg1 proteins 250:257 surface proteins 242:257 surface proteins 242:257 Aberrant glycosylation on surface proteins is associated with different cellular statuses and disease progression. 26894747 1 14 theme N-linked 141:148 arg1 glycans 150:156 N-linked glycans 141:156 N-linked glycans 141:156 The frequent modification of cell-surface proteins by N-linked glycans is known to be correlated with many biological processes. 26894747 4 15 theme mass 481:484 arg1 MS 500:501 MS 500:501 MS 500:501 Currently mass spectrometry (MS)-based proteomics provides the possibility to analyze the N-glycoproteome, but effective separation and enrichment methods are required for the analysis of surface glycoproteins prior to MS measurement. 26894747 4 15 theme mass 481:484 arg1 spectrometry 486:497 mass spectrometry 481:497 mass spectrometry (MS) 481:502 Currently mass spectrometry (MS)-based proteomics provides the possibility to analyze the N-glycoproteome, but effective separation and enrichment methods are required for the analysis of surface glycoproteins prior to MS measurement. 26894747 9 16 theme dolichol-linked 1764:1778 arg1 oligosaccharides 1790:1805 dolichol-linked precursor oligosaccharides 1764:1805 dolichol-linked precursor oligosaccharides 1764:1805 The quantification results demonstrated that many glycosylation sites on surface proteins were down-regulated in statin-treated cells compared to untreated cells because statin prevents the synthesis of dolichol, which is essential for the formation of dolichol-linked precursor oligosaccharides. 26894747 11 17 theme global 1968:1973 arg1 analysis 1975:1982 the global analysis 1964:1982 the global analysis of the cell-surface N-glycoproteome 1964:2018 This method can be extensively applied for the global analysis of the cell-surface N-glycoproteome. 26894747 2 18 theme cellular 288:295 arg1 statuses 297:304 different cellular statuses 278:304 different cellular statuses 278:304 Aberrant glycosylation on surface proteins is associated with different cellular statuses and disease progression. 26894747 5 19 dep visualization 797:809 arg1 the 786:788 the 786:788 the 786:788 The introduction of bio-orthogonal groups into proteins accelerates research in the robust visualization, identification, and quantification of proteins. 26894747 5 20 theme proteins 850:857 arg1 identification 812:825 identification 812:825 identification 812:825 The introduction of bio-orthogonal groups into proteins accelerates research in the robust visualization, identification, and quantification of proteins. 26894747 5 20 theme proteins 850:857 arg1 quantification 832:845 quantification 832:845 quantification 832:845 The introduction of bio-orthogonal groups into proteins accelerates research in the robust visualization, identification, and quantification of proteins. 26894747 5 20 theme proteins 850:857 arg1 visualization 797:809 robust visualization 790:809 robust visualization 790:809 The introduction of bio-orthogonal groups into proteins accelerates research in the robust visualization, identification, and quantification of proteins. 26894747 9 21 theme dolichol 1714:1721 arg1 synthesis 1701:1709 the synthesis 1697:1709 the synthesis 1697:1709 The quantification results demonstrated that many glycosylation sites on surface proteins were down-regulated in statin-treated cells compared to untreated cells because statin prevents the synthesis of dolichol, which is essential for the formation of dolichol-linked precursor oligosaccharides. 26894747 9 21 theme dolichol 1714:1721 arg1 essential 1733:1741 essential 1733:1741 essential 1733:1741 The quantification results demonstrated that many glycosylation sites on surface proteins were down-regulated in statin-treated cells compared to untreated cells because statin prevents the synthesis of dolichol, which is essential for the formation of dolichol-linked precursor oligosaccharides. 26894747 11 22 theme cell-surface 1991:2002 arg1 N-glycoproteome 2004:2018 the cell-surface N-glycoproteome 1987:2018 the cell-surface N-glycoproteome 1987:2018 This method can be extensively applied for the global analysis of the cell-surface N-glycoproteome. 26894747 8 23 gly N-glycosylated 1447:1460 arg1 sites 1462:1466 280 unique N-glycosylated sites 1436:1466 280 unique N-glycosylated sites 1436:1466 GalNAz was then employed for the quantification experiment in statin-treated HepG2 liver cells, and 280 unique N-glycosylated sites were quantified from 168 surface proteins. 26894747 4 24 gly glycoproteins 667:679 arg1 glycoproteins 667:679 surface glycoproteins 659:679 surface glycoproteins prior to MS measurement 659:703 Currently mass spectrometry (MS)-based proteomics provides the possibility to analyze the N-glycoproteome, but effective separation and enrichment methods are required for the analysis of surface glycoproteins prior to MS measurement. 26894747 7 25 from sites 1293:1297 arg1 experiments 1323:1333 biological duplicate experiments 1302:1333 biological duplicate experiments 1302:1333 Comparison of three sugar analogs, N-azidoacetylgalactosamine (GalNAz), N-azidoacetylglucosamine (GlcNAz), and N-azidoacetylmannosamine (ManNAz), showed that metabolic labeling with GalNAz resulted in the greatest number of glycoproteins and glycosylation sites in biological duplicate experiments. 26894747 1 26 theme proteins 129:136 arg1 modification 100:111 The frequent modification 87:111 The frequent modification of cell-surface proteins by N-linked glycans 87:156 The frequent modification of cell-surface proteins by N-linked glycans is known to be correlated with many biological processes. 26894747 7 27 theme analogs 1063:1069 arg1 Comparison 1037:1046 Comparison 1037:1046 Comparison of three sugar analogs, N-azidoacetylgalactosamine (GalNAz), N-azidoacetylglucosamine (GlcNAz), and N-azidoacetylmannosamine (ManNAz), 1037:1181 Comparison of three sugar analogs, N-azidoacetylgalactosamine (GalNAz), N-azidoacetylglucosamine (GlcNAz), and N-azidoacetylmannosamine (ManNAz), showed that metabolic labeling with GalNAz resulted in the greatest number of glycoproteins and glycosylation sites in biological duplicate experiments. 26894747 1 28 theme frequent 91:98 arg1 modification 100:111 The frequent modification 87:111 The frequent modification of cell-surface proteins by N-linked glycans 87:156 The frequent modification of cell-surface proteins by N-linked glycans is known to be correlated with many biological processes. 26894747 7 29 from experiments 1323:1333 arg1 number 1251:1256 the greatest number 1238:1256 the greatest number of glycoproteins and glycosylation sites in biological duplicate experiments 1238:1333 Comparison of three sugar analogs, N-azidoacetylgalactosamine (GalNAz), N-azidoacetylglucosamine (GlcNAz), and N-azidoacetylmannosamine (ManNAz), showed that metabolic labeling with GalNAz resulted in the greatest number of glycoproteins and glycosylation sites in biological duplicate experiments. 26894747 10 30 gly glycosylation 1816:1828 arg2 sites 1830:1834 Several glycosylation sites 1808:1834 Several glycosylation sites in proteins that participate in the Alzheimer's disease pathway 1808:1898 Several glycosylation sites in proteins that participate in the Alzheimer's disease pathway were down-regulated. 26894747 0 31 theme Site-Specific 0:12 arg1 Quantification 14:27 Site-Specific Quantification 0:27 Site-Specific Quantification of Surface N-Glycoproteins in Statin-Treated Liver Cells 0:84 Site-Specific Quantification of Surface N-Glycoproteins in Statin-Treated Liver Cells. 26894747 6 32 from analogs 915:921 arg1 analysis 930:937 the analysis 926:937 the analysis of cell-surface N-glycoproteins 926:969 Here we have comprehensively evaluated different sugar analogs in the analysis of cell-surface N-glycoproteins by combining copper-free click chemistry and MS-based proteomics. 26894747 3 33 theme located 437:443 arg1 glycoproteins 423:435 glycoproteins 423:435 glycoproteins located only on the cell surface 423:468 However, it is extraordinarily challenging to comprehensively and site-specifically analyze glycoproteins located only on the cell surface. 26894747 7 34 theme biological 1302:1311 arg1 experiments 1323:1333 biological duplicate experiments 1302:1333 biological duplicate experiments 1302:1333 Comparison of three sugar analogs, N-azidoacetylgalactosamine (GalNAz), N-azidoacetylglucosamine (GlcNAz), and N-azidoacetylmannosamine (ManNAz), showed that metabolic labeling with GalNAz resulted in the greatest number of glycoproteins and glycosylation sites in biological duplicate experiments. 26894747 6 35 theme copper-free 984:994 arg1 proteomics 1025:1034 copper-free click chemistry and MS-based proteomics 984:1034 copper-free click chemistry and MS-based proteomics 984:1034 Here we have comprehensively evaluated different sugar analogs in the analysis of cell-surface N-glycoproteins by combining copper-free click chemistry and MS-based proteomics. 26894747 9 36 theme precursor 1780:1788 arg1 oligosaccharides 1790:1805 dolichol-linked precursor oligosaccharides 1764:1805 dolichol-linked precursor oligosaccharides 1764:1805 The quantification results demonstrated that many glycosylation sites on surface proteins were down-regulated in statin-treated cells compared to untreated cells because statin prevents the synthesis of dolichol, which is essential for the formation of dolichol-linked precursor oligosaccharides. 26894747 9 37 gly glycosylation 1561:1573 arg2 sites 1575:1579 many glycosylation sites 1556:1579 many glycosylation sites on surface proteins 1556:1599 The quantification results demonstrated that many glycosylation sites on surface proteins were down-regulated in statin-treated cells compared to untreated cells because statin prevents the synthesis of dolichol, which is essential for the formation of dolichol-linked precursor oligosaccharides. 26894747 10 38 theme disease 1884:1890 arg1 pathway 1892:1898 the Alzheimer's disease pathway 1868:1898 the Alzheimer's disease pathway 1868:1898 Several glycosylation sites in proteins that participate in the Alzheimer's disease pathway were down-regulated. 26894747 0 39 theme N-Glycoproteins 40:54 arg1 Quantification 14:27 Site-Specific Quantification 0:27 Site-Specific Quantification of Surface N-Glycoproteins in Statin-Treated Liver Cells 0:84 Site-Specific Quantification of Surface N-Glycoproteins in Statin-Treated Liver Cells. 26894747 9 40 theme quantification 1515:1528 arg1 results 1530:1536 The quantification results 1511:1536 The quantification results 1511:1536 The quantification results demonstrated that many glycosylation sites on surface proteins were down-regulated in statin-treated cells compared to untreated cells because statin prevents the synthesis of dolichol, which is essential for the formation of dolichol-linked precursor oligosaccharides. 26894747 7 41 theme sites 1293:1297 arg1 number 1251:1256 the greatest number 1238:1256 the greatest number of glycoproteins and glycosylation sites in biological duplicate experiments 1238:1333 Comparison of three sugar analogs, N-azidoacetylgalactosamine (GalNAz), N-azidoacetylglucosamine (GlcNAz), and N-azidoacetylmannosamine (ManNAz), showed that metabolic labeling with GalNAz resulted in the greatest number of glycoproteins and glycosylation sites in biological duplicate experiments. 26894747 7 42 with labeling 1205:1212 arg1 GalNAz 1219:1224 GalNAz 1219:1224 GalNAz 1219:1224 Comparison of three sugar analogs, N-azidoacetylgalactosamine (GalNAz), N-azidoacetylglucosamine (GlcNAz), and N-azidoacetylmannosamine (ManNAz), showed that metabolic labeling with GalNAz resulted in the greatest number of glycoproteins and glycosylation sites in biological duplicate experiments. 26894747 3 43 theme cell 457:460 arg1 surface 462:468 the cell surface 453:468 the cell surface 453:468 However, it is extraordinarily challenging to comprehensively and site-specifically analyze glycoproteins located only on the cell surface. 26894747 4 44 theme effective 582:590 arg1 separation 592:601 effective separation and enrichment methods 582:624 separation 592:601 Currently mass spectrometry (MS)-based proteomics provides the possibility to analyze the N-glycoproteome, but effective separation and enrichment methods are required for the analysis of surface glycoproteins prior to MS measurement. 26894747 0 45 theme Statin-Treated 59:72 arg1 Cells 80:84 Statin-Treated Liver Cells 59:84 Statin-Treated Liver Cells 59:84 Site-Specific Quantification of Surface N-Glycoproteins in Statin-Treated Liver Cells. 26894747 6 46 theme cell-surface 942:953 arg1 N-glycoproteins 955:969 cell-surface N-glycoproteins 942:969 cell-surface N-glycoproteins 942:969 Here we have comprehensively evaluated different sugar analogs in the analysis of cell-surface N-glycoproteins by combining copper-free click chemistry and MS-based proteomics. 26894747 9 47 theme many 1556:1559 arg1 sites 1575:1579 many glycosylation sites 1556:1579 many glycosylation sites on surface proteins 1556:1599 The quantification results demonstrated that many glycosylation sites on surface proteins were down-regulated in statin-treated cells compared to untreated cells because statin prevents the synthesis of dolichol, which is essential for the formation of dolichol-linked precursor oligosaccharides. 26894747 4 48 theme glycoproteins 667:679 arg1 analysis 647:654 the analysis 643:654 the analysis of surface glycoproteins prior to MS measurement 643:703 Currently mass spectrometry (MS)-based proteomics provides the possibility to analyze the N-glycoproteome, but effective separation and enrichment methods are required for the analysis of surface glycoproteins prior to MS measurement. 26894747 9 49 theme statin-treated 1624:1637 arg1 cells 1639:1643 statin-treated cells 1624:1643 statin-treated cells 1624:1643 The quantification results demonstrated that many glycosylation sites on surface proteins were down-regulated in statin-treated cells compared to untreated cells because statin prevents the synthesis of dolichol, which is essential for the formation of dolichol-linked precursor oligosaccharides. 26894747 0 50 theme Liver 74:78 arg1 Cells 80:84 Statin-Treated Liver Cells 59:84 Statin-Treated Liver Cells 59:84 Site-Specific Quantification of Surface N-Glycoproteins in Statin-Treated Liver Cells. 26894747 9 51 theme surface 1584:1590 arg1 proteins 1592:1599 surface proteins 1584:1599 surface proteins 1584:1599 The quantification results demonstrated that many glycosylation sites on surface proteins were down-regulated in statin-treated cells compared to untreated cells because statin prevents the synthesis of dolichol, which is essential for the formation of dolichol-linked precursor oligosaccharides. 26894747 5 52 theme groups 741:746 arg1 introduction 710:721 The introduction 706:721 The introduction of bio-orthogonal groups into proteins 706:760 The introduction of bio-orthogonal groups into proteins accelerates research in the robust visualization, identification, and quantification of proteins. 26894747 6 53 theme MS-based 1016:1023 arg1 proteomics 1025:1034 copper-free click chemistry and MS-based proteomics 984:1034 copper-free click chemistry and MS-based proteomics 984:1034 Here we have comprehensively evaluated different sugar analogs in the analysis of cell-surface N-glycoproteins by combining copper-free click chemistry and MS-based proteomics. 26894747 6 54 theme different 899:907 arg1 analogs 915:921 different sugar analogs 899:921 different sugar analogs in the analysis of cell-surface N-glycoproteins 899:969 Here we have comprehensively evaluated different sugar analogs in the analysis of cell-surface N-glycoproteins by combining copper-free click chemistry and MS-based proteomics. 26894747 2 55 theme disease 310:316 arg1 progression 318:328 disease progression 310:328 disease progression 310:328 Aberrant glycosylation on surface proteins is associated with different cellular statuses and disease progression. 26894747 2 56 from glycosylation 225:237 arg1 proteins 250:257 surface proteins 242:257 surface proteins 242:257 Aberrant glycosylation on surface proteins is associated with different cellular statuses and disease progression. 26894747 6 57 theme chemistry 1002:1010 arg1 proteomics 1025:1034 copper-free click chemistry and MS-based proteomics 984:1034 copper-free click chemistry and MS-based proteomics 984:1034 Here we have comprehensively evaluated different sugar analogs in the analysis of cell-surface N-glycoproteins by combining copper-free click chemistry and MS-based proteomics. 26894747 4 58 theme enrichment 607:616 arg1 methods 618:624 effective separation and enrichment methods 582:624 methods 618:624 Currently mass spectrometry (MS)-based proteomics provides the possibility to analyze the N-glycoproteome, but effective separation and enrichment methods are required for the analysis of surface glycoproteins prior to MS measurement. 26894747 10 59 theme glycosylation 1816:1828 arg1 sites 1830:1834 Several glycosylation sites 1808:1834 Several glycosylation sites in proteins that participate in the Alzheimer's disease pathway 1808:1898 Several glycosylation sites in proteins that participate in the Alzheimer's disease pathway were down-regulated. 26894747 1 60 theme biological 194:203 arg1 processes 205:213 many biological processes 189:213 many biological processes 189:213 The frequent modification of cell-surface proteins by N-linked glycans is known to be correlated with many biological processes. 26894747 8 61 theme statin-treated 1398:1411 arg1 cells 1425:1429 statin-treated HepG2 liver cells 1398:1429 statin-treated HepG2 liver cells 1398:1429 GalNAz was then employed for the quantification experiment in statin-treated HepG2 liver cells, and 280 unique N-glycosylated sites were quantified from 168 surface proteins. 26894747 7 62 theme metabolic 1195:1203 arg1 labeling 1205:1212 metabolic labeling 1195:1212 metabolic labeling with GalNAz 1195:1224 Comparison of three sugar analogs, N-azidoacetylgalactosamine (GalNAz), N-azidoacetylglucosamine (GlcNAz), and N-azidoacetylmannosamine (ManNAz), showed that metabolic labeling with GalNAz resulted in the greatest number of glycoproteins and glycosylation sites in biological duplicate experiments. 26894747 4 63 theme -based 503:508 arg1 proteomics 510:519 mass spectrometry (MS)-based proteomics 481:519 mass spectrometry (MS)-based proteomics 481:519 Currently mass spectrometry (MS)-based proteomics provides the possibility to analyze the N-glycoproteome, but effective separation and enrichment methods are required for the analysis of surface glycoproteins prior to MS measurement. 26894747 8 64 theme liver 1419:1423 arg1 cells 1425:1429 statin-treated HepG2 liver cells 1398:1429 statin-treated HepG2 liver cells 1398:1429 GalNAz was then employed for the quantification experiment in statin-treated HepG2 liver cells, and 280 unique N-glycosylated sites were quantified from 168 surface proteins. 26894747 2 65 gly glycosylation 225:237 arg1 proteins 250:257 surface proteins 242:257 surface proteins 242:257 Aberrant glycosylation on surface proteins is associated with different cellular statuses and disease progression. 26894747 8 66 from experiment 1384:1393 arg1 cells 1425:1429 statin-treated HepG2 liver cells 1398:1429 statin-treated HepG2 liver cells 1398:1429 GalNAz was then employed for the quantification experiment in statin-treated HepG2 liver cells, and 280 unique N-glycosylated sites were quantified from 168 surface proteins. 26894747 8 67 theme N-glycosylated 1447:1460 arg1 sites 1462:1466 280 unique N-glycosylated sites 1436:1466 280 unique N-glycosylated sites 1436:1466 GalNAz was then employed for the quantification experiment in statin-treated HepG2 liver cells, and 280 unique N-glycosylated sites were quantified from 168 surface proteins. 26894747 2 68 theme different 278:286 arg1 statuses 297:304 different cellular statuses 278:304 different cellular statuses 278:304 Aberrant glycosylation on surface proteins is associated with different cellular statuses and disease progression. 26894747 7 69 from glycoproteins 1261:1273 arg1 experiments 1323:1333 biological duplicate experiments 1302:1333 biological duplicate experiments 1302:1333 Comparison of three sugar analogs, N-azidoacetylgalactosamine (GalNAz), N-azidoacetylglucosamine (GlcNAz), and N-azidoacetylmannosamine (ManNAz), showed that metabolic labeling with GalNAz resulted in the greatest number of glycoproteins and glycosylation sites in biological duplicate experiments. 26894747 0 70 from Quantification 14:27 arg1 Cells 80:84 Statin-Treated Liver Cells 59:84 Statin-Treated Liver Cells 59:84 Site-Specific Quantification of Surface N-Glycoproteins in Statin-Treated Liver Cells. 26894747 11 71 theme N-glycoproteome 2004:2018 arg1 analysis 1975:1982 the global analysis 1964:1982 the global analysis of the cell-surface N-glycoproteome 1964:2018 This method can be extensively applied for the global analysis of the cell-surface N-glycoproteome. 26894747 8 72 theme surface 1493:1499 arg1 proteins 1501:1508 168 surface proteins 1489:1508 168 surface proteins 1489:1508 GalNAz was then employed for the quantification experiment in statin-treated HepG2 liver cells, and 280 unique N-glycosylated sites were quantified from 168 surface proteins. 26894747 7 73 theme duplicate 1313:1321 arg1 experiments 1323:1333 biological duplicate experiments 1302:1333 biological duplicate experiments 1302:1333 Comparison of three sugar analogs, N-azidoacetylgalactosamine (GalNAz), N-azidoacetylglucosamine (GlcNAz), and N-azidoacetylmannosamine (ManNAz), showed that metabolic labeling with GalNAz resulted in the greatest number of glycoproteins and glycosylation sites in biological duplicate experiments. 26894747 0 74 theme Surface 32:38 arg1 N-Glycoproteins 40:54 Surface N-Glycoproteins 32:54 Surface N-Glycoproteins 32:54 Site-Specific Quantification of Surface N-Glycoproteins in Statin-Treated Liver Cells. 26894747 3 75 gly glycoproteins 423:435 arg1 glycoproteins 423:435 glycoproteins 423:435 glycoproteins located only on the cell surface 423:468 However, it is extraordinarily challenging to comprehensively and site-specifically analyze glycoproteins located only on the cell surface. 26894747 7 76 theme sugar 1057:1061 arg1 analogs 1063:1069 three sugar analogs 1051:1069 three sugar analogs 1051:1069 Comparison of three sugar analogs, N-azidoacetylgalactosamine (GalNAz), N-azidoacetylglucosamine (GlcNAz), and N-azidoacetylmannosamine (ManNAz), showed that metabolic labeling with GalNAz resulted in the greatest number of glycoproteins and glycosylation sites in biological duplicate experiments. 26894747 7 76 theme sugar 1057:1061 arg1 N-azidoacetylglucosamine 1109:1132 N-azidoacetylglucosamine 1109:1132 N-azidoacetylglucosamine (GlcNAz) 1109:1141 Comparison of three sugar analogs, N-azidoacetylgalactosamine (GalNAz), N-azidoacetylglucosamine (GlcNAz), and N-azidoacetylmannosamine (ManNAz), showed that metabolic labeling with GalNAz resulted in the greatest number of glycoproteins and glycosylation sites in biological duplicate experiments. 26894747 7 76 theme sugar 1057:1061 arg1 N-azidoacetylgalactosamine 1072:1097 N-azidoacetylgalactosamine 1072:1097 N-azidoacetylgalactosamine (GalNAz) 1072:1106 Comparison of three sugar analogs, N-azidoacetylgalactosamine (GalNAz), N-azidoacetylglucosamine (GlcNAz), and N-azidoacetylmannosamine (ManNAz), showed that metabolic labeling with GalNAz resulted in the greatest number of glycoproteins and glycosylation sites in biological duplicate experiments. 26894747 7 76 theme sugar 1057:1061 arg1 N-azidoacetylmannosamine 1148:1171 N-azidoacetylmannosamine 1148:1171 N-azidoacetylmannosamine (ManNAz) 1148:1180 Comparison of three sugar analogs, N-azidoacetylgalactosamine (GalNAz), N-azidoacetylglucosamine (GlcNAz), and N-azidoacetylmannosamine (ManNAz), showed that metabolic labeling with GalNAz resulted in the greatest number of glycoproteins and glycosylation sites in biological duplicate experiments. 26894747 1 77 theme cell-surface 116:127 arg1 proteins 129:136 cell-surface proteins 116:136 cell-surface proteins 116:136 The frequent modification of cell-surface proteins by N-linked glycans is known to be correlated with many biological processes. 26894747 6 78 gly N-glycoproteins 955:969 arg1 N-glycoproteins 955:969 cell-surface N-glycoproteins 942:969 cell-surface N-glycoproteins 942:969 Here we have comprehensively evaluated different sugar analogs in the analysis of cell-surface N-glycoproteins by combining copper-free click chemistry and MS-based proteomics. 26894747 7 79 theme glycosylation 1279:1291 arg1 sites 1293:1297 glycosylation sites 1279:1297 glycosylation sites 1279:1297 Comparison of three sugar analogs, N-azidoacetylgalactosamine (GalNAz), N-azidoacetylglucosamine (GlcNAz), and N-azidoacetylmannosamine (ManNAz), showed that metabolic labeling with GalNAz resulted in the greatest number of glycoproteins and glycosylation sites in biological duplicate experiments. 26894747 9 80 theme oligosaccharides 1790:1805 arg1 formation 1751:1759 the formation 1747:1759 the formation of dolichol-linked precursor oligosaccharides 1747:1805 The quantification results demonstrated that many glycosylation sites on surface proteins were down-regulated in statin-treated cells compared to untreated cells because statin prevents the synthesis of dolichol, which is essential for the formation of dolichol-linked precursor oligosaccharides. 26894747 7 81 gly glycosylation 1279:1291 arg2 sites 1293:1297 glycosylation sites 1279:1297 glycosylation sites 1279:1297 Comparison of three sugar analogs, N-azidoacetylgalactosamine (GalNAz), N-azidoacetylglucosamine (GlcNAz), and N-azidoacetylmannosamine (ManNAz), showed that metabolic labeling with GalNAz resulted in the greatest number of glycoproteins and glycosylation sites in biological duplicate experiments. 26894747 7 82 theme glycoproteins 1261:1273 arg1 number 1251:1256 the greatest number 1238:1256 the greatest number of glycoproteins and glycosylation sites in biological duplicate experiments 1238:1333 Comparison of three sugar analogs, N-azidoacetylgalactosamine (GalNAz), N-azidoacetylglucosamine (GlcNAz), and N-azidoacetylmannosamine (ManNAz), showed that metabolic labeling with GalNAz resulted in the greatest number of glycoproteins and glycosylation sites in biological duplicate experiments. 26894747 9 83 from sites 1575:1579 arg1 proteins 1592:1599 surface proteins 1584:1599 surface proteins 1584:1599 The quantification results demonstrated that many glycosylation sites on surface proteins were down-regulated in statin-treated cells compared to untreated cells because statin prevents the synthesis of dolichol, which is essential for the formation of dolichol-linked precursor oligosaccharides. 26894747 6 84 theme N-glycoproteins 955:969 arg1 analysis 930:937 the analysis 926:937 the analysis of cell-surface N-glycoproteins 926:969 Here we have comprehensively evaluated different sugar analogs in the analysis of cell-surface N-glycoproteins by combining copper-free click chemistry and MS-based proteomics. 26894747 7 85 from number 1251:1256 arg1 experiments 1323:1333 biological duplicate experiments 1302:1333 biological duplicate experiments 1302:1333 Comparison of three sugar analogs, N-azidoacetylgalactosamine (GalNAz), N-azidoacetylglucosamine (GlcNAz), and N-azidoacetylmannosamine (ManNAz), showed that metabolic labeling with GalNAz resulted in the greatest number of glycoproteins and glycosylation sites in biological duplicate experiments. 26894747 7 86 gly glycoproteins 1261:1273 arg1 glycoproteins 1261:1273 glycoproteins 1261:1273 glycoproteins 1261:1273 Comparison of three sugar analogs, N-azidoacetylgalactosamine (GalNAz), N-azidoacetylglucosamine (GlcNAz), and N-azidoacetylmannosamine (ManNAz), showed that metabolic labeling with GalNAz resulted in the greatest number of glycoproteins and glycosylation sites in biological duplicate experiments. 26894747 4 87 theme prior 681:685 arg1 glycoproteins 667:679 surface glycoproteins 659:679 surface glycoproteins prior to MS measurement 659:703 Currently mass spectrometry (MS)-based proteomics provides the possibility to analyze the N-glycoproteome, but effective separation and enrichment methods are required for the analysis of surface glycoproteins prior to MS measurement. 26894747 1 88 link N-linked 141:148 arg1 glycans 150:156 N-linked glycans 141:156 N-linked glycans 141:156 The frequent modification of cell-surface proteins by N-linked glycans is known to be correlated with many biological processes. 26894747 2 89 theme Aberrant 216:223 arg1 glycosylation 225:237 Aberrant glycosylation 216:237 Aberrant glycosylation on surface proteins 216:257 Aberrant glycosylation on surface proteins is associated with different cellular statuses and disease progression. 26894747 9 90 theme glycosylation 1561:1573 arg1 sites 1575:1579 many glycosylation sites 1556:1579 many glycosylation sites on surface proteins 1556:1599 The quantification results demonstrated that many glycosylation sites on surface proteins were down-regulated in statin-treated cells compared to untreated cells because statin prevents the synthesis of dolichol, which is essential for the formation of dolichol-linked precursor oligosaccharides. 26894747 9 91 link dolichol-linked 1764:1778 arg1 oligosaccharides 1790:1805 dolichol-linked precursor oligosaccharides 1764:1805 dolichol-linked precursor oligosaccharides 1764:1805 The quantification results demonstrated that many glycosylation sites on surface proteins were down-regulated in statin-treated cells compared to untreated cells because statin prevents the synthesis of dolichol, which is essential for the formation of dolichol-linked precursor oligosaccharides. 26894747 4 92 theme MS 690:691 arg1 measurement 693:703 MS measurement 690:703 MS measurement 690:703 Currently mass spectrometry (MS)-based proteomics provides the possibility to analyze the N-glycoproteome, but effective separation and enrichment methods are required for the analysis of surface glycoproteins prior to MS measurement. 25236766 5 0 from residues 893:900 arg1 directions 910:919 both directions 905:919 both directions 905:919 The nearest O-glycosylation residues are Thr58 and Thr71; therefore, four amino acid residues intervene between the epitope and those residues in both directions. 25236766 0 1 theme O-glycosylation-independent 70:96 arg1 binding 98:104 O-glycosylation-independent binding 70:104 O-glycosylation-independent binding 70:104 An antibody reactive to the Gly63-Lys68 epitope of NT-proBNP exhibits O-glycosylation-independent binding. 25236766 3 2 gly deglycosylated 539:552 arg1 form 554:557 its deglycosylated form 535:557 its deglycosylated form 535:557 We developed an antibody that binds to the recombinant NT-proBNP protein and its deglycosylated form with similar affinities in an enzyme immunoassay. 25236766 3 3 from affinities 572:581 arg1 immunoassay 596:606 an enzyme immunoassay 586:606 an enzyme immunoassay 586:606 We developed an antibody that binds to the recombinant NT-proBNP protein and its deglycosylated form with similar affinities in an enzyme immunoassay. 25236766 5 4 theme nearest 763:769 arg1 Thr58 800:804 Thr58 800:804 Thr58 800:804 The nearest O-glycosylation residues are Thr58 and Thr71; therefore, four amino acid residues intervene between the epitope and those residues in both directions. 25236766 5 4 theme nearest 763:769 arg1 residues 787:794 The nearest O-glycosylation residues 759:794 The nearest O-glycosylation residues 759:794 The nearest O-glycosylation residues are Thr58 and Thr71; therefore, four amino acid residues intervene between the epitope and those residues in both directions. 25236766 2 5 theme heavy 330:334 arg1 glycosylation 345:357 heavy O-linked glycosylation 330:357 heavy O-linked glycosylation 330:357 NT-proBNP exhibits heavy O-linked glycosylation, and it is quite difficult to develop an antibody that exhibits glycosylation-independent binding. 25236766 1 6 theme biological 272:281 arg1 function 283:290 its biological function 268:290 its biological function 268:290 The N-terminal fragment of prohormone brain natriuretic peptide (NT-proBNP) is a commonly used biomarker for the diagnosis of congestive heart failure, although its biological function is not well known. 25236766 5 7 theme O-glycosylation 771:785 arg1 Thr58 800:804 Thr58 800:804 Thr58 800:804 The nearest O-glycosylation residues are Thr58 and Thr71; therefore, four amino acid residues intervene between the epitope and those residues in both directions. 25236766 5 7 theme O-glycosylation 771:785 arg1 residues 787:794 The nearest O-glycosylation residues 759:794 The nearest O-glycosylation residues 759:794 The nearest O-glycosylation residues are Thr58 and Thr71; therefore, four amino acid residues intervene between the epitope and those residues in both directions. 25236766 4 8 with assay 728:732 arg1 peptide 741:747 a peptide mimotope 739:756 a peptide mimotope 739:756 The epitope was defined as Gly63-Lys68 based on mimetic peptide screening, site-directed mutagenesis and a competition assay with a peptide mimotope. 25236766 4 9 theme site-directed 684:696 arg1 screening 673:681 mimetic peptide screening 657:681 mimetic peptide screening 657:681 The epitope was defined as Gly63-Lys68 based on mimetic peptide screening, site-directed mutagenesis and a competition assay with a peptide mimotope. 25236766 4 9 theme site-directed 684:696 arg1 mutagenesis 698:708 site-directed mutagenesis 684:708 site-directed mutagenesis 684:708 The epitope was defined as Gly63-Lys68 based on mimetic peptide screening, site-directed mutagenesis and a competition assay with a peptide mimotope. 25236766 6 10 theme O-glycosylation-independent 1010:1036 arg1 binding 1038:1044 O-glycosylation-independent binding 1010:1044 O-glycosylation-independent binding 1010:1044 In conclusion, we report that an antibody reactive to Gly63-Lys68 of NT-proBNP exhibits O-glycosylation-independent binding. 25236766 1 11 theme congestive 233:242 arg1 failure 250:256 congestive heart failure 233:256 congestive heart failure 233:256 The N-terminal fragment of prohormone brain natriuretic peptide (NT-proBNP) is a commonly used biomarker for the diagnosis of congestive heart failure, although its biological function is not well known. 25236766 5 12 theme amino 833:837 arg1 residues 844:851 four amino acid residues 828:851 four amino acid residues 828:851 The nearest O-glycosylation residues are Thr58 and Thr71; therefore, four amino acid residues intervene between the epitope and those residues in both directions. 25236766 3 13 theme enzyme 589:594 arg1 immunoassay 596:606 an enzyme immunoassay 586:606 an enzyme immunoassay 586:606 We developed an antibody that binds to the recombinant NT-proBNP protein and its deglycosylated form with similar affinities in an enzyme immunoassay. 25236766 5 14 theme acid 839:842 arg1 residues 844:851 four amino acid residues 828:851 four amino acid residues 828:851 The nearest O-glycosylation residues are Thr58 and Thr71; therefore, four amino acid residues intervene between the epitope and those residues in both directions. 25236766 4 15 theme mimotope 749:756 arg1 peptide 741:747 a peptide mimotope 739:756 a peptide mimotope 739:756 The epitope was defined as Gly63-Lys68 based on mimetic peptide screening, site-directed mutagenesis and a competition assay with a peptide mimotope. 25236766 1 16 theme used 197:200 arg1 biomarker 202:210 a commonly used biomarker 186:210 a commonly used biomarker for the diagnosis of congestive heart failure 186:256 The N-terminal fragment of prohormone brain natriuretic peptide (NT-proBNP) is a commonly used biomarker for the diagnosis of congestive heart failure, although its biological function is not well known. 25236766 1 16 theme used 197:200 arg1 fragment 122:129 The N-terminal fragment 107:129 The N-terminal fragment of prohormone brain natriuretic peptide (NT-proBNP) 107:181 The N-terminal fragment of prohormone brain natriuretic peptide (NT-proBNP) is a commonly used biomarker for the diagnosis of congestive heart failure, although its biological function is not well known. 25236766 6 17 theme NT-proBNP 991:999 arg1 Gly63-Lys68 976:986 Gly63-Lys68 976:986 Gly63-Lys68 of NT-proBNP 976:999 In conclusion, we report that an antibody reactive to Gly63-Lys68 of NT-proBNP exhibits O-glycosylation-independent binding. 25236766 1 18 theme N-terminal 111:120 arg1 biomarker 202:210 a commonly used biomarker 186:210 a commonly used biomarker for the diagnosis of congestive heart failure 186:256 The N-terminal fragment of prohormone brain natriuretic peptide (NT-proBNP) is a commonly used biomarker for the diagnosis of congestive heart failure, although its biological function is not well known. 25236766 1 18 theme N-terminal 111:120 arg1 fragment 122:129 The N-terminal fragment 107:129 The N-terminal fragment of prohormone brain natriuretic peptide (NT-proBNP) 107:181 The N-terminal fragment of prohormone brain natriuretic peptide (NT-proBNP) is a commonly used biomarker for the diagnosis of congestive heart failure, although its biological function is not well known. 25236766 2 19 theme glycosylation-independent 423:447 arg1 binding 449:455 glycosylation-independent binding 423:455 glycosylation-independent binding 423:455 NT-proBNP exhibits heavy O-linked glycosylation, and it is quite difficult to develop an antibody that exhibits glycosylation-independent binding. 25236766 0 20 theme reactive 12:19 arg1 antibody 3:10 An antibody 0:10 An antibody reactive to the Gly63-Lys68 epitope of NT-proBNP 0:59 An antibody reactive to the Gly63-Lys68 epitope of NT-proBNP exhibits O-glycosylation-independent binding. 25236766 4 21 theme competition 716:726 arg1 assay 728:732 a competition assay 714:732 a competition assay with a peptide mimotope 714:756 The epitope was defined as Gly63-Lys68 based on mimetic peptide screening, site-directed mutagenesis and a competition assay with a peptide mimotope. 25236766 4 21 theme competition 716:726 arg1 screening 673:681 mimetic peptide screening 657:681 mimetic peptide screening 657:681 The epitope was defined as Gly63-Lys68 based on mimetic peptide screening, site-directed mutagenesis and a competition assay with a peptide mimotope. 25236766 0 22 theme Gly63-Lys68 28:38 arg1 epitope 40:46 the Gly63-Lys68 epitope 24:46 the Gly63-Lys68 epitope of NT-proBNP 24:59 An antibody reactive to the Gly63-Lys68 epitope of NT-proBNP exhibits O-glycosylation-independent binding. 25236766 1 23 theme prohormone 134:143 arg1 NT-proBNP 172:180 NT-proBNP 172:180 NT-proBNP 172:180 The N-terminal fragment of prohormone brain natriuretic peptide (NT-proBNP) is a commonly used biomarker for the diagnosis of congestive heart failure, although its biological function is not well known. 25236766 1 23 theme prohormone 134:143 arg1 peptide 163:169 prohormone brain natriuretic peptide 134:169 prohormone brain natriuretic peptide (NT-proBNP) 134:181 The N-terminal fragment of prohormone brain natriuretic peptide (NT-proBNP) is a commonly used biomarker for the diagnosis of congestive heart failure, although its biological function is not well known. 25236766 4 24 with mutagenesis 698:708 arg1 peptide 741:747 a peptide mimotope 739:756 a peptide mimotope 739:756 The epitope was defined as Gly63-Lys68 based on mimetic peptide screening, site-directed mutagenesis and a competition assay with a peptide mimotope. 25236766 5 25 from epitope 875:881 arg1 directions 910:919 both directions 905:919 both directions 905:919 The nearest O-glycosylation residues are Thr58 and Thr71; therefore, four amino acid residues intervene between the epitope and those residues in both directions. 25236766 4 26 theme peptide 665:671 arg1 assay 728:732 a competition assay 714:732 a competition assay with a peptide mimotope 714:756 The epitope was defined as Gly63-Lys68 based on mimetic peptide screening, site-directed mutagenesis and a competition assay with a peptide mimotope. 25236766 4 26 theme peptide 665:671 arg1 screening 673:681 mimetic peptide screening 657:681 mimetic peptide screening 657:681 The epitope was defined as Gly63-Lys68 based on mimetic peptide screening, site-directed mutagenesis and a competition assay with a peptide mimotope. 25236766 4 26 theme peptide 665:671 arg1 mutagenesis 698:708 site-directed mutagenesis 684:708 site-directed mutagenesis 684:708 The epitope was defined as Gly63-Lys68 based on mimetic peptide screening, site-directed mutagenesis and a competition assay with a peptide mimotope. 25236766 6 27 theme reactive 964:971 arg1 antibody 955:962 an antibody 952:962 an antibody reactive to Gly63-Lys68 of NT-proBNP 952:999 In conclusion, we report that an antibody reactive to Gly63-Lys68 of NT-proBNP exhibits O-glycosylation-independent binding. 25236766 3 28 theme recombinant 501:511 arg1 protein 523:529 the recombinant NT-proBNP protein 497:529 the recombinant NT-proBNP protein 497:529 We developed an antibody that binds to the recombinant NT-proBNP protein and its deglycosylated form with similar affinities in an enzyme immunoassay. 25236766 3 29 theme NT-proBNP 513:521 arg1 protein 523:529 the recombinant NT-proBNP protein 497:529 the recombinant NT-proBNP protein 497:529 We developed an antibody that binds to the recombinant NT-proBNP protein and its deglycosylated form with similar affinities in an enzyme immunoassay. 25236766 1 30 theme brain 145:149 arg1 NT-proBNP 172:180 NT-proBNP 172:180 NT-proBNP 172:180 The N-terminal fragment of prohormone brain natriuretic peptide (NT-proBNP) is a commonly used biomarker for the diagnosis of congestive heart failure, although its biological function is not well known. 25236766 1 30 theme brain 145:149 arg1 peptide 163:169 prohormone brain natriuretic peptide 134:169 prohormone brain natriuretic peptide (NT-proBNP) 134:181 The N-terminal fragment of prohormone brain natriuretic peptide (NT-proBNP) is a commonly used biomarker for the diagnosis of congestive heart failure, although its biological function is not well known. 25236766 3 31 theme similar 564:570 arg1 affinities 572:581 similar affinities 564:581 similar affinities in an enzyme immunoassay 564:606 We developed an antibody that binds to the recombinant NT-proBNP protein and its deglycosylated form with similar affinities in an enzyme immunoassay. 25236766 1 32 theme natriuretic 151:161 arg1 NT-proBNP 172:180 NT-proBNP 172:180 NT-proBNP 172:180 The N-terminal fragment of prohormone brain natriuretic peptide (NT-proBNP) is a commonly used biomarker for the diagnosis of congestive heart failure, although its biological function is not well known. 25236766 1 32 theme natriuretic 151:161 arg1 peptide 163:169 prohormone brain natriuretic peptide 134:169 prohormone brain natriuretic peptide (NT-proBNP) 134:181 The N-terminal fragment of prohormone brain natriuretic peptide (NT-proBNP) is a commonly used biomarker for the diagnosis of congestive heart failure, although its biological function is not well known. 25236766 2 33 theme O-linked 336:343 arg1 glycosylation 345:357 heavy O-linked glycosylation 330:357 heavy O-linked glycosylation 330:357 NT-proBNP exhibits heavy O-linked glycosylation, and it is quite difficult to develop an antibody that exhibits glycosylation-independent binding. 25236766 4 34 theme mimetic 657:663 arg1 assay 728:732 a competition assay 714:732 a competition assay with a peptide mimotope 714:756 The epitope was defined as Gly63-Lys68 based on mimetic peptide screening, site-directed mutagenesis and a competition assay with a peptide mimotope. 25236766 4 34 theme mimetic 657:663 arg1 screening 673:681 mimetic peptide screening 657:681 mimetic peptide screening 657:681 The epitope was defined as Gly63-Lys68 based on mimetic peptide screening, site-directed mutagenesis and a competition assay with a peptide mimotope. 25236766 4 34 theme mimetic 657:663 arg1 mutagenesis 698:708 site-directed mutagenesis 684:708 site-directed mutagenesis 684:708 The epitope was defined as Gly63-Lys68 based on mimetic peptide screening, site-directed mutagenesis and a competition assay with a peptide mimotope. 25236766 1 35 theme peptide 163:169 arg1 biomarker 202:210 a commonly used biomarker 186:210 a commonly used biomarker for the diagnosis of congestive heart failure 186:256 The N-terminal fragment of prohormone brain natriuretic peptide (NT-proBNP) is a commonly used biomarker for the diagnosis of congestive heart failure, although its biological function is not well known. 25236766 1 35 theme peptide 163:169 arg1 fragment 122:129 The N-terminal fragment 107:129 The N-terminal fragment of prohormone brain natriuretic peptide (NT-proBNP) 107:181 The N-terminal fragment of prohormone brain natriuretic peptide (NT-proBNP) is a commonly used biomarker for the diagnosis of congestive heart failure, although its biological function is not well known. 25236766 1 36 theme heart 244:248 arg1 failure 250:256 congestive heart failure 233:256 congestive heart failure 233:256 The N-terminal fragment of prohormone brain natriuretic peptide (NT-proBNP) is a commonly used biomarker for the diagnosis of congestive heart failure, although its biological function is not well known. 25236766 0 37 theme NT-proBNP 51:59 arg1 epitope 40:46 the Gly63-Lys68 epitope 24:46 the Gly63-Lys68 epitope of NT-proBNP 24:59 An antibody reactive to the Gly63-Lys68 epitope of NT-proBNP exhibits O-glycosylation-independent binding. 25236766 2 38 link O-linked 336:343 arg1 glycosylation 345:357 heavy O-linked glycosylation 330:357 heavy O-linked glycosylation 330:357 NT-proBNP exhibits heavy O-linked glycosylation, and it is quite difficult to develop an antibody that exhibits glycosylation-independent binding. 25236766 3 39 theme deglycosylated 539:552 arg1 form 554:557 its deglycosylated form 535:557 its deglycosylated form 535:557 We developed an antibody that binds to the recombinant NT-proBNP protein and its deglycosylated form with similar affinities in an enzyme immunoassay. 25236766 1 40 theme failure 250:256 arg1 diagnosis 220:228 the diagnosis 216:228 the diagnosis of congestive heart failure 216:256 The N-terminal fragment of prohormone brain natriuretic peptide (NT-proBNP) is a commonly used biomarker for the diagnosis of congestive heart failure, although its biological function is not well known. 25761681 0 0 theme mass 89:92 arg1 identification 108:121 mass spectrometric identification 89:121 mass spectrometric identification 89:121 Rat liver sinusoidal surface N-linked glycoproteomic analysis by affinity enrichment and mass spectrometric identification. 25761681 6 1 theme liver 1099:1103 arg1 surface 1116:1122 the liver sinusoidal surface 1095:1122 the liver sinusoidal surface 1095:1122 Moreover, 23 cluster of differentiation antigens with 49 glycopeptides were detected within the membrane glycoproteins of the liver sinusoidal surface. 25761681 6 2 gly glycoproteins 1078:1090 arg1 glycoproteins 1078:1090 the membrane glycoproteins 1065:1090 the membrane glycoproteins of the liver sinusoidal surface 1065:1122 Moreover, 23 cluster of differentiation antigens with 49 glycopeptides were detected within the membrane glycoproteins of the liver sinusoidal surface. 25761681 3 3 from glycosylation 423:435 arg1 LSEC 504:507 LSEC 504:507 LSEC 504:507 To analyze glycosylation of plasma membrane proteins in liver sinusoidal endothelial cells (LSEC), N-glycopeptides of the LSEC surface were enriched using a filter-assisted sample preparation-based lectin affinity capture method and subsequently identified with mass spectrometry. 25761681 3 3 from glycosylation 423:435 arg1 cells 497:501 liver sinusoidal endothelial cells 468:501 liver sinusoidal endothelial cells (LSEC) 468:508 To analyze glycosylation of plasma membrane proteins in liver sinusoidal endothelial cells (LSEC), N-glycopeptides of the LSEC surface were enriched using a filter-assisted sample preparation-based lectin affinity capture method and subsequently identified with mass spectrometry. 25761681 3 4 gly glycosylation 423:435 arg1 proteins 456:463 plasma membrane proteins 440:463 plasma membrane proteins in liver sinusoidal endothelial cells (LSEC) 440:508 To analyze glycosylation of plasma membrane proteins in liver sinusoidal endothelial cells (LSEC), N-glycopeptides of the LSEC surface were enriched using a filter-assisted sample preparation-based lectin affinity capture method and subsequently identified with mass spectrometry. 25761681 6 5 theme sinusoidal 1105:1114 arg1 surface 1116:1122 the liver sinusoidal surface 1095:1122 the liver sinusoidal surface 1095:1122 Moreover, 23 cluster of differentiation antigens with 49 glycopeptides were detected within the membrane glycoproteins of the liver sinusoidal surface. 25761681 2 6 theme liver 373:377 arg1 cancer 379:384 liver cancer 373:384 liver cancer 373:384 It plays critical roles in many physiological and pathological processes by virtue of its unique location at the blood-tissue interface, including angiogenesis, liver cancer, cirrhosis, and fibrosis. 25761681 2 7 from interface 338:346 arg1 location 309:316 its unique location 298:316 its unique location at the blood-tissue interface 298:346 It plays critical roles in many physiological and pathological processes by virtue of its unique location at the blood-tissue interface, including angiogenesis, liver cancer, cirrhosis, and fibrosis. 25761681 2 7 from interface 338:346 arg1 virtue 288:293 virtue 288:293 virtue of its unique location at the blood-tissue interface 288:346 It plays critical roles in many physiological and pathological processes by virtue of its unique location at the blood-tissue interface, including angiogenesis, liver cancer, cirrhosis, and fibrosis. 25761681 3 8 theme lectin 610:615 arg1 method 634:639 a filter-assisted sample preparation-based lectin affinity capture method 567:639 a filter-assisted sample preparation-based lectin affinity capture method 567:639 To analyze glycosylation of plasma membrane proteins in liver sinusoidal endothelial cells (LSEC), N-glycopeptides of the LSEC surface were enriched using a filter-assisted sample preparation-based lectin affinity capture method and subsequently identified with mass spectrometry. 25761681 2 9 theme location 309:316 arg1 virtue 288:293 virtue 288:293 virtue of its unique location at the blood-tissue interface 288:346 It plays critical roles in many physiological and pathological processes by virtue of its unique location at the blood-tissue interface, including angiogenesis, liver cancer, cirrhosis, and fibrosis. 25761681 0 10 theme spectrometric 94:106 arg1 identification 108:121 mass spectrometric identification 89:121 mass spectrometric identification 89:121 Rat liver sinusoidal surface N-linked glycoproteomic analysis by affinity enrichment and mass spectrometric identification. 25761681 2 11 theme unique 302:307 arg1 location 309:316 its unique location 298:316 its unique location at the blood-tissue interface 298:346 It plays critical roles in many physiological and pathological processes by virtue of its unique location at the blood-tissue interface, including angiogenesis, liver cancer, cirrhosis, and fibrosis. 25761681 5 12 gly glycoproteins 860:872 arg1 glycoproteins 860:872 the glycoproteins 856:872 the glycoproteins 856:872 Among the glycoproteins, 53% were classified as plasma membrane proteins and 47 (31%) as signaling proteins and receptors. 25761681 8 13 theme surface 1315:1321 arg1 analysis 1282:1289 N-glycoproteomic analysis 1265:1289 N-glycoproteomic analysis of the liver sinusoidal surface 1265:1321 Therefore, N-glycoproteomic analysis of the liver sinusoidal surface may provide useful information on liver regeneration and facilitate liver disease diagnosis. 25761681 3 14 theme surface 539:545 arg1 N-glycopeptides 511:525 N-glycopeptides 511:525 N-glycopeptides of the LSEC surface 511:545 To analyze glycosylation of plasma membrane proteins in liver sinusoidal endothelial cells (LSEC), N-glycopeptides of the LSEC surface were enriched using a filter-assisted sample preparation-based lectin affinity capture method and subsequently identified with mass spectrometry. 25761681 3 15 theme plasma 440:445 arg1 proteins 456:463 plasma membrane proteins 440:463 plasma membrane proteins in liver sinusoidal endothelial cells (LSEC) 440:508 To analyze glycosylation of plasma membrane proteins in liver sinusoidal endothelial cells (LSEC), N-glycopeptides of the LSEC surface were enriched using a filter-assisted sample preparation-based lectin affinity capture method and subsequently identified with mass spectrometry. 25761681 1 16 theme important 179:187 arg1 modifications 197:209 the most biologically important protein modifications 157:209 the most biologically important protein modifications 157:209 Glycosylation in liver is one of the most biologically important protein modifications. 25761681 3 17 gly N-glycopeptides 511:525 arg1 surface 539:545 the LSEC surface 530:545 the LSEC surface 530:545 To analyze glycosylation of plasma membrane proteins in liver sinusoidal endothelial cells (LSEC), N-glycopeptides of the LSEC surface were enriched using a filter-assisted sample preparation-based lectin affinity capture method and subsequently identified with mass spectrometry. 25761681 3 17 gly N-glycopeptides 511:525 arg2 N-glycopeptides 511:525 N-glycopeptides 511:525 N-glycopeptides of the LSEC surface 511:545 To analyze glycosylation of plasma membrane proteins in liver sinusoidal endothelial cells (LSEC), N-glycopeptides of the LSEC surface were enriched using a filter-assisted sample preparation-based lectin affinity capture method and subsequently identified with mass spectrometry. 25761681 1 18 theme protein 189:195 arg1 modifications 197:209 the most biologically important protein modifications 157:209 the most biologically important protein modifications 157:209 Glycosylation in liver is one of the most biologically important protein modifications. 25761681 7 19 theme identified 1192:1201 arg1 glycoproteins 1203:1215 identified glycoproteins 1192:1215 identified glycoproteins 1192:1215 Furthermore, bioinformatics analysis revealed that the majority of identified glycoproteins have an impact on processes of LSEC. 25761681 3 20 theme sample 585:590 arg1 method 634:639 a filter-assisted sample preparation-based lectin affinity capture method 567:639 a filter-assisted sample preparation-based lectin affinity capture method 567:639 To analyze glycosylation of plasma membrane proteins in liver sinusoidal endothelial cells (LSEC), N-glycopeptides of the LSEC surface were enriched using a filter-assisted sample preparation-based lectin affinity capture method and subsequently identified with mass spectrometry. 25761681 6 21 theme membrane 1069:1076 arg1 glycoproteins 1078:1090 the membrane glycoproteins 1065:1090 the membrane glycoproteins of the liver sinusoidal surface 1065:1122 Moreover, 23 cluster of differentiation antigens with 49 glycopeptides were detected within the membrane glycoproteins of the liver sinusoidal surface. 25761681 1 22 theme modifications 197:209 arg1 modifications 197:209 the most biologically important protein modifications 157:209 the most biologically important protein modifications 157:209 Glycosylation in liver is one of the most biologically important protein modifications. 25761681 1 22 theme modifications 197:209 arg1 one 150:152 one 150:152 one 150:152 Glycosylation in liver is one of the most biologically important protein modifications. 25761681 0 23 theme Rat 0:2 arg1 liver 4:8 Rat liver 0:8 Rat liver 0:8 Rat liver sinusoidal surface N-linked glycoproteomic analysis by affinity enrichment and mass spectrometric identification. 25761681 2 24 theme blood-tissue 325:336 arg1 interface 338:346 the blood-tissue interface 321:346 the blood-tissue interface 321:346 It plays critical roles in many physiological and pathological processes by virtue of its unique location at the blood-tissue interface, including angiogenesis, liver cancer, cirrhosis, and fibrosis. 25761681 3 25 theme membrane 447:454 arg1 proteins 456:463 plasma membrane proteins 440:463 plasma membrane proteins in liver sinusoidal endothelial cells (LSEC) 440:508 To analyze glycosylation of plasma membrane proteins in liver sinusoidal endothelial cells (LSEC), N-glycopeptides of the LSEC surface were enriched using a filter-assisted sample preparation-based lectin affinity capture method and subsequently identified with mass spectrometry. 25761681 0 26 theme surface 21:27 arg1 analysis 53:60 surface N-linked glycoproteomic analysis 21:60 surface N-linked glycoproteomic analysis by affinity enrichment and mass spectrometric identification 21:121 Rat liver sinusoidal surface N-linked glycoproteomic analysis by affinity enrichment and mass spectrometric identification. 25761681 4 27 gly glycoproteins 743:755 arg1 glycoproteins 743:755 152 glycoproteins 739:755 152 glycoproteins 739:755 In total, 225 unique N-glycosylation sites on 152 glycoproteins were identified, of which 119 (53%) sites had not previously been determined experimentally. 25761681 0 28 link N-linked 29:36 arg1 analysis 53:60 surface N-linked glycoproteomic analysis 21:60 surface N-linked glycoproteomic analysis by affinity enrichment and mass spectrometric identification 21:121 Rat liver sinusoidal surface N-linked glycoproteomic analysis by affinity enrichment and mass spectrometric identification. 25761681 5 29 theme signaling 939:947 arg1 proteins 949:956 signaling proteins 939:956 signaling proteins 939:956 Among the glycoproteins, 53% were classified as plasma membrane proteins and 47 (31%) as signaling proteins and receptors. 25761681 5 29 theme signaling 939:947 arg1 % 877:877 53% 875:877 53% 875:877 Among the glycoproteins, 53% were classified as plasma membrane proteins and 47 (31%) as signaling proteins and receptors. 25761681 8 30 from information 1342:1352 arg1 regeneration 1363:1374 liver regeneration 1357:1374 liver regeneration 1357:1374 Therefore, N-glycoproteomic analysis of the liver sinusoidal surface may provide useful information on liver regeneration and facilitate liver disease diagnosis. 25761681 3 31 theme endothelial 485:495 arg1 LSEC 504:507 LSEC 504:507 LSEC 504:507 To analyze glycosylation of plasma membrane proteins in liver sinusoidal endothelial cells (LSEC), N-glycopeptides of the LSEC surface were enriched using a filter-assisted sample preparation-based lectin affinity capture method and subsequently identified with mass spectrometry. 25761681 3 31 theme endothelial 485:495 arg1 cells 497:501 liver sinusoidal endothelial cells 468:501 liver sinusoidal endothelial cells (LSEC) 468:508 To analyze glycosylation of plasma membrane proteins in liver sinusoidal endothelial cells (LSEC), N-glycopeptides of the LSEC surface were enriched using a filter-assisted sample preparation-based lectin affinity capture method and subsequently identified with mass spectrometry. 25761681 3 32 theme preparation-based 592:608 arg1 method 634:639 a filter-assisted sample preparation-based lectin affinity capture method 567:639 a filter-assisted sample preparation-based lectin affinity capture method 567:639 To analyze glycosylation of plasma membrane proteins in liver sinusoidal endothelial cells (LSEC), N-glycopeptides of the LSEC surface were enriched using a filter-assisted sample preparation-based lectin affinity capture method and subsequently identified with mass spectrometry. 25761681 8 33 theme disease 1397:1403 arg1 diagnosis 1405:1413 liver disease diagnosis 1391:1413 liver disease diagnosis 1391:1413 Therefore, N-glycoproteomic analysis of the liver sinusoidal surface may provide useful information on liver regeneration and facilitate liver disease diagnosis. 25761681 3 34 theme filter-assisted 569:583 arg1 method 634:639 a filter-assisted sample preparation-based lectin affinity capture method 567:639 a filter-assisted sample preparation-based lectin affinity capture method 567:639 To analyze glycosylation of plasma membrane proteins in liver sinusoidal endothelial cells (LSEC), N-glycopeptides of the LSEC surface were enriched using a filter-assisted sample preparation-based lectin affinity capture method and subsequently identified with mass spectrometry. 25761681 2 35 from virtue 288:293 arg1 interface 338:346 the blood-tissue interface 321:346 the blood-tissue interface 321:346 It plays critical roles in many physiological and pathological processes by virtue of its unique location at the blood-tissue interface, including angiogenesis, liver cancer, cirrhosis, and fibrosis. 25761681 6 36 theme surface 1116:1122 arg1 glycoproteins 1078:1090 the membrane glycoproteins 1065:1090 the membrane glycoproteins of the liver sinusoidal surface 1065:1122 Moreover, 23 cluster of differentiation antigens with 49 glycopeptides were detected within the membrane glycoproteins of the liver sinusoidal surface. 25761681 0 37 theme glycoproteomic 38:51 arg1 analysis 53:60 surface N-linked glycoproteomic analysis 21:60 surface N-linked glycoproteomic analysis by affinity enrichment and mass spectrometric identification 21:121 Rat liver sinusoidal surface N-linked glycoproteomic analysis by affinity enrichment and mass spectrometric identification. 25761681 4 38 theme unique 707:712 arg1 sites 730:734 225 unique N-glycosylation sites 703:734 225 unique N-glycosylation sites on 152 glycoproteins 703:755 In total, 225 unique N-glycosylation sites on 152 glycoproteins were identified, of which 119 (53%) sites had not previously been determined experimentally. 25761681 6 39 gly glycopeptides 1030:1042 arg2 glycopeptides 1030:1042 49 glycopeptides 1027:1042 49 glycopeptides 1027:1042 Moreover, 23 cluster of differentiation antigens with 49 glycopeptides were detected within the membrane glycoproteins of the liver sinusoidal surface. 25761681 4 40 from sites 730:734 arg1 glycoproteins 743:755 152 glycoproteins 739:755 152 glycoproteins 739:755 In total, 225 unique N-glycosylation sites on 152 glycoproteins were identified, of which 119 (53%) sites had not previously been determined experimentally. 25761681 3 41 theme capture 626:632 arg1 method 634:639 a filter-assisted sample preparation-based lectin affinity capture method 567:639 a filter-assisted sample preparation-based lectin affinity capture method 567:639 To analyze glycosylation of plasma membrane proteins in liver sinusoidal endothelial cells (LSEC), N-glycopeptides of the LSEC surface were enriched using a filter-assisted sample preparation-based lectin affinity capture method and subsequently identified with mass spectrometry. 25761681 8 42 theme N-glycoproteomic 1265:1280 arg1 analysis 1282:1289 N-glycoproteomic analysis 1265:1289 N-glycoproteomic analysis of the liver sinusoidal surface 1265:1321 Therefore, N-glycoproteomic analysis of the liver sinusoidal surface may provide useful information on liver regeneration and facilitate liver disease diagnosis. 25761681 3 43 theme liver 468:472 arg1 LSEC 504:507 LSEC 504:507 LSEC 504:507 To analyze glycosylation of plasma membrane proteins in liver sinusoidal endothelial cells (LSEC), N-glycopeptides of the LSEC surface were enriched using a filter-assisted sample preparation-based lectin affinity capture method and subsequently identified with mass spectrometry. 25761681 3 43 theme liver 468:472 arg1 cells 497:501 liver sinusoidal endothelial cells 468:501 liver sinusoidal endothelial cells (LSEC) 468:508 To analyze glycosylation of plasma membrane proteins in liver sinusoidal endothelial cells (LSEC), N-glycopeptides of the LSEC surface were enriched using a filter-assisted sample preparation-based lectin affinity capture method and subsequently identified with mass spectrometry. 25761681 0 44 theme N-linked 29:36 arg1 analysis 53:60 surface N-linked glycoproteomic analysis 21:60 surface N-linked glycoproteomic analysis by affinity enrichment and mass spectrometric identification 21:121 Rat liver sinusoidal surface N-linked glycoproteomic analysis by affinity enrichment and mass spectrometric identification. 25761681 3 45 theme mass 674:677 arg1 spectrometry 679:690 mass spectrometry 674:690 mass spectrometry 674:690 To analyze glycosylation of plasma membrane proteins in liver sinusoidal endothelial cells (LSEC), N-glycopeptides of the LSEC surface were enriched using a filter-assisted sample preparation-based lectin affinity capture method and subsequently identified with mass spectrometry. 25761681 2 46 theme physiological 244:256 arg1 angiogenesis 359:370 angiogenesis 359:370 angiogenesis 359:370 It plays critical roles in many physiological and pathological processes by virtue of its unique location at the blood-tissue interface, including angiogenesis, liver cancer, cirrhosis, and fibrosis. 25761681 2 46 theme physiological 244:256 arg1 processes 275:283 many physiological and pathological processes 239:283 many physiological and pathological processes 239:283 It plays critical roles in many physiological and pathological processes by virtue of its unique location at the blood-tissue interface, including angiogenesis, liver cancer, cirrhosis, and fibrosis. 25761681 2 46 theme physiological 244:256 arg1 fibrosis 402:409 fibrosis 402:409 fibrosis 402:409 It plays critical roles in many physiological and pathological processes by virtue of its unique location at the blood-tissue interface, including angiogenesis, liver cancer, cirrhosis, and fibrosis. 25761681 2 46 theme physiological 244:256 arg1 cirrhosis 387:395 cirrhosis 387:395 cirrhosis 387:395 It plays critical roles in many physiological and pathological processes by virtue of its unique location at the blood-tissue interface, including angiogenesis, liver cancer, cirrhosis, and fibrosis. 25761681 2 46 theme physiological 244:256 arg1 cancer 379:384 liver cancer 373:384 liver cancer 373:384 It plays critical roles in many physiological and pathological processes by virtue of its unique location at the blood-tissue interface, including angiogenesis, liver cancer, cirrhosis, and fibrosis. 25761681 3 47 theme sinusoidal 474:483 arg1 LSEC 504:507 LSEC 504:507 LSEC 504:507 To analyze glycosylation of plasma membrane proteins in liver sinusoidal endothelial cells (LSEC), N-glycopeptides of the LSEC surface were enriched using a filter-assisted sample preparation-based lectin affinity capture method and subsequently identified with mass spectrometry. 25761681 3 47 theme sinusoidal 474:483 arg1 cells 497:501 liver sinusoidal endothelial cells 468:501 liver sinusoidal endothelial cells (LSEC) 468:508 To analyze glycosylation of plasma membrane proteins in liver sinusoidal endothelial cells (LSEC), N-glycopeptides of the LSEC surface were enriched using a filter-assisted sample preparation-based lectin affinity capture method and subsequently identified with mass spectrometry. 25761681 7 48 theme bioinformatics 1138:1151 arg1 analysis 1153:1160 bioinformatics analysis 1138:1160 bioinformatics analysis 1138:1160 Furthermore, bioinformatics analysis revealed that the majority of identified glycoproteins have an impact on processes of LSEC. 25761681 4 49 gly N-glycosylation 714:728 arg2 225 703:705 225 703:705 225 703:705 In total, 225 unique N-glycosylation sites on 152 glycoproteins were identified, of which 119 (53%) sites had not previously been determined experimentally. 25761681 4 49 gly N-glycosylation 714:728 arg2 sites 730:734 225 unique N-glycosylation sites 703:734 225 unique N-glycosylation sites on 152 glycoproteins 703:755 In total, 225 unique N-glycosylation sites on 152 glycoproteins were identified, of which 119 (53%) sites had not previously been determined experimentally. 25761681 3 50 theme proteins 456:463 arg1 glycosylation 423:435 glycosylation 423:435 glycosylation of plasma membrane proteins in liver sinusoidal endothelial cells (LSEC) 423:508 To analyze glycosylation of plasma membrane proteins in liver sinusoidal endothelial cells (LSEC), N-glycopeptides of the LSEC surface were enriched using a filter-assisted sample preparation-based lectin affinity capture method and subsequently identified with mass spectrometry. 25761681 2 51 theme many 239:242 arg1 angiogenesis 359:370 angiogenesis 359:370 angiogenesis 359:370 It plays critical roles in many physiological and pathological processes by virtue of its unique location at the blood-tissue interface, including angiogenesis, liver cancer, cirrhosis, and fibrosis. 25761681 2 51 theme many 239:242 arg1 processes 275:283 many physiological and pathological processes 239:283 many physiological and pathological processes 239:283 It plays critical roles in many physiological and pathological processes by virtue of its unique location at the blood-tissue interface, including angiogenesis, liver cancer, cirrhosis, and fibrosis. 25761681 2 51 theme many 239:242 arg1 fibrosis 402:409 fibrosis 402:409 fibrosis 402:409 It plays critical roles in many physiological and pathological processes by virtue of its unique location at the blood-tissue interface, including angiogenesis, liver cancer, cirrhosis, and fibrosis. 25761681 2 51 theme many 239:242 arg1 cirrhosis 387:395 cirrhosis 387:395 cirrhosis 387:395 It plays critical roles in many physiological and pathological processes by virtue of its unique location at the blood-tissue interface, including angiogenesis, liver cancer, cirrhosis, and fibrosis. 25761681 2 51 theme many 239:242 arg1 cancer 379:384 liver cancer 373:384 liver cancer 373:384 It plays critical roles in many physiological and pathological processes by virtue of its unique location at the blood-tissue interface, including angiogenesis, liver cancer, cirrhosis, and fibrosis. 25761681 7 52 contain have 1217:1220 arg1 majority 1180:1187 the majority 1176:1187 the majority of identified glycoproteins 1176:1215 Furthermore, bioinformatics analysis revealed that the majority of identified glycoproteins have an impact on processes of LSEC. 25761681 7 52 contain have 1217:1220 arg2 impact 1225:1230 an impact 1222:1230 an impact on processes of LSEC 1222:1251 Furthermore, bioinformatics analysis revealed that the majority of identified glycoproteins have an impact on processes of LSEC. 25761681 8 53 theme liver 1357:1361 arg1 regeneration 1363:1374 liver regeneration 1357:1374 liver regeneration 1357:1374 Therefore, N-glycoproteomic analysis of the liver sinusoidal surface may provide useful information on liver regeneration and facilitate liver disease diagnosis. 25761681 3 54 theme affinity 617:624 arg1 method 634:639 a filter-assisted sample preparation-based lectin affinity capture method 567:639 a filter-assisted sample preparation-based lectin affinity capture method 567:639 To analyze glycosylation of plasma membrane proteins in liver sinusoidal endothelial cells (LSEC), N-glycopeptides of the LSEC surface were enriched using a filter-assisted sample preparation-based lectin affinity capture method and subsequently identified with mass spectrometry. 25761681 7 55 from impact 1225:1230 arg1 processes 1235:1243 processes 1235:1243 processes of LSEC 1235:1251 Furthermore, bioinformatics analysis revealed that the majority of identified glycoproteins have an impact on processes of LSEC. 25761681 6 56 with cluster 986:992 arg1 glycopeptides 1030:1042 49 glycopeptides 1027:1042 49 glycopeptides 1027:1042 Moreover, 23 cluster of differentiation antigens with 49 glycopeptides were detected within the membrane glycoproteins of the liver sinusoidal surface. 25761681 8 57 theme sinusoidal 1304:1313 arg1 surface 1315:1321 the liver sinusoidal surface 1294:1321 the liver sinusoidal surface 1294:1321 Therefore, N-glycoproteomic analysis of the liver sinusoidal surface may provide useful information on liver regeneration and facilitate liver disease diagnosis. 25761681 2 58 theme critical 221:228 arg1 roles 230:234 critical roles 221:234 critical roles 221:234 It plays critical roles in many physiological and pathological processes by virtue of its unique location at the blood-tissue interface, including angiogenesis, liver cancer, cirrhosis, and fibrosis. 25761681 7 59 gly glycoproteins 1203:1215 arg1 glycoproteins 1203:1215 identified glycoproteins 1192:1215 identified glycoproteins 1192:1215 Furthermore, bioinformatics analysis revealed that the majority of identified glycoproteins have an impact on processes of LSEC. 25761681 3 60 from cells 497:501 arg1 glycosylation 423:435 glycosylation 423:435 glycosylation of plasma membrane proteins in liver sinusoidal endothelial cells (LSEC) 423:508 To analyze glycosylation of plasma membrane proteins in liver sinusoidal endothelial cells (LSEC), N-glycopeptides of the LSEC surface were enriched using a filter-assisted sample preparation-based lectin affinity capture method and subsequently identified with mass spectrometry. 25761681 8 61 theme useful 1335:1340 arg1 information 1342:1352 useful information 1335:1352 useful information on liver regeneration 1335:1374 Therefore, N-glycoproteomic analysis of the liver sinusoidal surface may provide useful information on liver regeneration and facilitate liver disease diagnosis. 25761681 1 62 from Glycosylation 124:136 arg1 liver 141:145 liver 141:145 liver 141:145 Glycosylation in liver is one of the most biologically important protein modifications. 25761681 8 63 theme liver 1298:1302 arg1 surface 1315:1321 the liver sinusoidal surface 1294:1321 the liver sinusoidal surface 1294:1321 Therefore, N-glycoproteomic analysis of the liver sinusoidal surface may provide useful information on liver regeneration and facilitate liver disease diagnosis. 25761681 8 64 theme liver 1391:1395 arg1 diagnosis 1405:1413 liver disease diagnosis 1391:1413 liver disease diagnosis 1391:1413 Therefore, N-glycoproteomic analysis of the liver sinusoidal surface may provide useful information on liver regeneration and facilitate liver disease diagnosis. 25761681 4 65 theme N-glycosylation 714:728 arg1 sites 730:734 225 unique N-glycosylation sites 703:734 225 unique N-glycosylation sites on 152 glycoproteins 703:755 In total, 225 unique N-glycosylation sites on 152 glycoproteins were identified, of which 119 (53%) sites had not previously been determined experimentally. 25761681 7 66 theme LSEC 1248:1251 arg1 processes 1235:1243 processes 1235:1243 processes of LSEC 1235:1251 Furthermore, bioinformatics analysis revealed that the majority of identified glycoproteins have an impact on processes of LSEC. 25761681 5 67 theme membrane 905:912 arg1 proteins 914:921 plasma membrane proteins 898:921 plasma membrane proteins 898:921 Among the glycoproteins, 53% were classified as plasma membrane proteins and 47 (31%) as signaling proteins and receptors. 25761681 5 67 theme membrane 905:912 arg1 % 877:877 53% 875:877 53% 875:877 Among the glycoproteins, 53% were classified as plasma membrane proteins and 47 (31%) as signaling proteins and receptors. 25761681 5 68 theme plasma 898:903 arg1 proteins 914:921 plasma membrane proteins 898:921 plasma membrane proteins 898:921 Among the glycoproteins, 53% were classified as plasma membrane proteins and 47 (31%) as signaling proteins and receptors. 25761681 5 68 theme plasma 898:903 arg1 % 877:877 53% 875:877 53% 875:877 Among the glycoproteins, 53% were classified as plasma membrane proteins and 47 (31%) as signaling proteins and receptors. 25761681 6 69 theme antigens 1013:1020 arg1 cluster 986:992 23 cluster 983:992 23 cluster of differentiation antigens with 49 glycopeptides 983:1042 Moreover, 23 cluster of differentiation antigens with 49 glycopeptides were detected within the membrane glycoproteins of the liver sinusoidal surface. 25761681 0 70 theme affinity 65:72 arg1 enrichment 74:83 affinity enrichment 65:83 affinity enrichment 65:83 Rat liver sinusoidal surface N-linked glycoproteomic analysis by affinity enrichment and mass spectrometric identification. 25761681 6 71 located detected 1049:1056 arg1 glycoproteins 1078:1090 the membrane glycoproteins 1065:1090 the membrane glycoproteins of the liver sinusoidal surface 1065:1122 Moreover, 23 cluster of differentiation antigens with 49 glycopeptides were detected within the membrane glycoproteins of the liver sinusoidal surface. 25761681 6 71 located detected 1049:1056 arg2 cluster 986:992 23 cluster 983:992 23 cluster of differentiation antigens with 49 glycopeptides 983:1042 Moreover, 23 cluster of differentiation antigens with 49 glycopeptides were detected within the membrane glycoproteins of the liver sinusoidal surface. 25761681 2 72 theme pathological 262:273 arg1 angiogenesis 359:370 angiogenesis 359:370 angiogenesis 359:370 It plays critical roles in many physiological and pathological processes by virtue of its unique location at the blood-tissue interface, including angiogenesis, liver cancer, cirrhosis, and fibrosis. 25761681 2 72 theme pathological 262:273 arg1 processes 275:283 many physiological and pathological processes 239:283 many physiological and pathological processes 239:283 It plays critical roles in many physiological and pathological processes by virtue of its unique location at the blood-tissue interface, including angiogenesis, liver cancer, cirrhosis, and fibrosis. 25761681 2 72 theme pathological 262:273 arg1 fibrosis 402:409 fibrosis 402:409 fibrosis 402:409 It plays critical roles in many physiological and pathological processes by virtue of its unique location at the blood-tissue interface, including angiogenesis, liver cancer, cirrhosis, and fibrosis. 25761681 2 72 theme pathological 262:273 arg1 cirrhosis 387:395 cirrhosis 387:395 cirrhosis 387:395 It plays critical roles in many physiological and pathological processes by virtue of its unique location at the blood-tissue interface, including angiogenesis, liver cancer, cirrhosis, and fibrosis. 25761681 2 72 theme pathological 262:273 arg1 cancer 379:384 liver cancer 373:384 liver cancer 373:384 It plays critical roles in many physiological and pathological processes by virtue of its unique location at the blood-tissue interface, including angiogenesis, liver cancer, cirrhosis, and fibrosis. 25761681 3 73 from proteins 456:463 arg1 LSEC 504:507 LSEC 504:507 LSEC 504:507 To analyze glycosylation of plasma membrane proteins in liver sinusoidal endothelial cells (LSEC), N-glycopeptides of the LSEC surface were enriched using a filter-assisted sample preparation-based lectin affinity capture method and subsequently identified with mass spectrometry. 25761681 3 73 from proteins 456:463 arg1 cells 497:501 liver sinusoidal endothelial cells 468:501 liver sinusoidal endothelial cells (LSEC) 468:508 To analyze glycosylation of plasma membrane proteins in liver sinusoidal endothelial cells (LSEC), N-glycopeptides of the LSEC surface were enriched using a filter-assisted sample preparation-based lectin affinity capture method and subsequently identified with mass spectrometry. 25761681 3 74 theme LSEC 534:537 arg1 surface 539:545 the LSEC surface 530:545 the LSEC surface 530:545 To analyze glycosylation of plasma membrane proteins in liver sinusoidal endothelial cells (LSEC), N-glycopeptides of the LSEC surface were enriched using a filter-assisted sample preparation-based lectin affinity capture method and subsequently identified with mass spectrometry. 25761681 7 75 theme glycoproteins 1203:1215 arg1 majority 1180:1187 the majority 1176:1187 the majority of identified glycoproteins 1176:1215 Furthermore, bioinformatics analysis revealed that the majority of identified glycoproteins have an impact on processes of LSEC. 25761681 6 76 theme differentiation 997:1011 arg1 antigens 1013:1020 differentiation antigens 997:1020 differentiation antigens 997:1020 Moreover, 23 cluster of differentiation antigens with 49 glycopeptides were detected within the membrane glycoproteins of the liver sinusoidal surface. 24673753 6 0 theme trisaccharide 1062:1074 arg1 HexNAc-HexNAc-Hex 1076:1092 a trisaccharide HexNAc-HexNAc-Hex 1060:1092 a trisaccharide HexNAc-HexNAc-Hex 1060:1092 Mass spectrometry analysis revealed that these proteins are modified with a trisaccharide HexNAc-HexNAc-Hex, which is unrelated to the O-antigen biosynthetic process. 24673753 6 0 theme trisaccharide 1062:1074 arg1 unrelated 1104:1112 unrelated 1104:1112 unrelated 1104:1112 Mass spectrometry analysis revealed that these proteins are modified with a trisaccharide HexNAc-HexNAc-Hex, which is unrelated to the O-antigen biosynthetic process. 24673753 1 1 theme complex 157:163 arg1 pathogens 175:183 pathogens 175:183 pathogens of humans, plants, and animals 175:214 Bacteria of the Burkholderia cepacia complex (Bcc) are pathogens of humans, plants, and animals. 24673753 1 1 theme complex 157:163 arg1 Bacteria 120:127 Bacteria 120:127 Bacteria of the Burkholderia cepacia complex (Bcc) 120:169 Bacteria of the Burkholderia cepacia complex (Bcc) are pathogens of humans, plants, and animals. 24673753 8 2 theme reduced 1341:1347 arg1 motility 1358:1365 reduced swimming motility 1341:1365 reduced swimming motility 1341:1365 Disruption of bcal0960 abolished glycosylation and resulted in reduced swimming motility and attenuated virulence towards both plant and insect model organisms. 24673753 7 3 theme glycosylation 1157:1169 arg1 sites 1171:1175 The glycosylation sites 1153:1175 The glycosylation sites that were identified 1153:1196 The glycosylation sites that were identified existed within regions of low complexity, rich in serine, alanine, and proline. 24673753 5 4 from responsible 897:907 arg1 B cenocepacia K56-2 866:884 B cenocepacia K56-2 866:884 B cenocepacia K56-2 866:884 In B cenocepacia K56-2, PglLBc is responsible for the glycosylation of 23 proteins involved in diverse cellular processes. 24673753 8 5 dep organisms 1428:1436 arg1 both 1400:1403 both 1400:1403 both 1400:1403 Disruption of bcal0960 abolished glycosylation and resulted in reduced swimming motility and attenuated virulence towards both plant and insect model organisms. 24673753 8 5 dep organisms 1428:1436 arg1 insect 1415:1420 insect 1415:1420 insect 1415:1420 Disruption of bcal0960 abolished glycosylation and resulted in reduced swimming motility and attenuated virulence towards both plant and insect model organisms. 24673753 4 6 theme gene 549:552 arg1 bcal0960 554:561 the cloned gene bcal0960 538:561 the cloned gene bcal0960 538:561 The PglLBc O-oligosaccharyltransferase (O-OTase), encoded by the cloned gene bcal0960, was shown to be capable of transferring a heptasaccharide from the Campylobacter jejuni N-glycosylation system to a Neisseria meningitides-derived acceptor protein in an Escherichia coli background, indicating that the enzyme has relaxed specificities for both the sugar donor and protein acceptor. 24673753 4 7 theme PglLBc 481:486 arg1 capable 580:586 capable 580:586 capable 580:586 The PglLBc O-oligosaccharyltransferase (O-OTase), encoded by the cloned gene bcal0960, was shown to be capable of transferring a heptasaccharide from the Campylobacter jejuni N-glycosylation system to a Neisseria meningitides-derived acceptor protein in an Escherichia coli background, indicating that the enzyme has relaxed specificities for both the sugar donor and protein acceptor. 24673753 4 7 theme PglLBc 481:486 arg1 O-OTase 517:523 O-OTase 517:523 O-OTase 517:523 The PglLBc O-oligosaccharyltransferase (O-OTase), encoded by the cloned gene bcal0960, was shown to be capable of transferring a heptasaccharide from the Campylobacter jejuni N-glycosylation system to a Neisseria meningitides-derived acceptor protein in an Escherichia coli background, indicating that the enzyme has relaxed specificities for both the sugar donor and protein acceptor. 24673753 4 7 theme PglLBc 481:486 arg1 O-oligosaccharyltransferase 488:514 The PglLBc O-oligosaccharyltransferase 477:514 The PglLBc O-oligosaccharyltransferase (O-OTase) 477:524 The PglLBc O-oligosaccharyltransferase (O-OTase), encoded by the cloned gene bcal0960, was shown to be capable of transferring a heptasaccharide from the Campylobacter jejuni N-glycosylation system to a Neisseria meningitides-derived acceptor protein in an Escherichia coli background, indicating that the enzyme has relaxed specificities for both the sugar donor and protein acceptor. 24673753 3 8 link O-linked 414:421 arg1 system 445:450 a general O-linked protein glycosylation system 404:450 a general O-linked protein glycosylation system in B. cenocepacia K56-2 404:474 In this study, we characterized a general O-linked protein glycosylation system in B. cenocepacia K56-2. 24673753 2 9 theme common 261:266 arg1 species 272:278 the most common Bcc species 252:278 the most common Bcc species infecting cystic fibrosis (CF) patients 252:318 Burkholderia cenocepacia is one of the most common Bcc species infecting cystic fibrosis (CF) patients and its carriage is associated with poor prognosis. 24673753 5 10 theme diverse 958:964 arg1 processes 975:983 diverse cellular processes 958:983 diverse cellular processes 958:983 In B cenocepacia K56-2, PglLBc is responsible for the glycosylation of 23 proteins involved in diverse cellular processes. 24673753 9 11 theme first 1467:1471 arg1 example 1473:1479 the first example 1463:1479 the first example of post-translational modification in Bcc 1463:1521 This study demonstrates the first example of post-translational modification in Bcc with implications for pathogenesis. 24673753 4 12 theme Escherichia 734:744 arg1 background 751:760 an Escherichia coli background 731:760 an Escherichia coli background 731:760 The PglLBc O-oligosaccharyltransferase (O-OTase), encoded by the cloned gene bcal0960, was shown to be capable of transferring a heptasaccharide from the Campylobacter jejuni N-glycosylation system to a Neisseria meningitides-derived acceptor protein in an Escherichia coli background, indicating that the enzyme has relaxed specificities for both the sugar donor and protein acceptor. 24673753 7 13 from proline 1269:1275 arg1 rich 1240:1243 rich 1240:1243 rich 1240:1243 The glycosylation sites that were identified existed within regions of low complexity, rich in serine, alanine, and proline. 24673753 4 14 theme Neisseria 680:688 arg1 protein 720:726 a Neisseria meningitides-derived acceptor protein 678:726 a Neisseria meningitides-derived acceptor protein in an Escherichia coli background 678:760 The PglLBc O-oligosaccharyltransferase (O-OTase), encoded by the cloned gene bcal0960, was shown to be capable of transferring a heptasaccharide from the Campylobacter jejuni N-glycosylation system to a Neisseria meningitides-derived acceptor protein in an Escherichia coli background, indicating that the enzyme has relaxed specificities for both the sugar donor and protein acceptor. 24673753 6 15 theme spectrometry 991:1002 arg1 analysis 1004:1011 Mass spectrometry analysis 986:1011 Mass spectrometry analysis 986:1011 Mass spectrometry analysis revealed that these proteins are modified with a trisaccharide HexNAc-HexNAc-Hex, which is unrelated to the O-antigen biosynthetic process. 24673753 7 16 theme low 1224:1226 arg1 complexity 1228:1237 low complexity 1224:1237 low complexity 1224:1237 The glycosylation sites that were identified existed within regions of low complexity, rich in serine, alanine, and proline. 24673753 3 17 theme protein 423:429 arg1 system 445:450 a general O-linked protein glycosylation system 404:450 a general O-linked protein glycosylation system in B. cenocepacia K56-2 404:474 In this study, we characterized a general O-linked protein glycosylation system in B. cenocepacia K56-2. 24673753 8 18 theme model 1422:1426 arg1 organisms 1428:1436 both plant and insect model organisms 1400:1436 both plant and insect model organisms 1400:1436 Disruption of bcal0960 abolished glycosylation and resulted in reduced swimming motility and attenuated virulence towards both plant and insect model organisms. 24673753 2 19 theme poor 356:359 arg1 prognosis 361:369 poor prognosis 356:369 poor prognosis 356:369 Burkholderia cenocepacia is one of the most common Bcc species infecting cystic fibrosis (CF) patients and its carriage is associated with poor prognosis. 24673753 7 20 theme complexity 1228:1237 arg1 regions 1213:1219 regions 1213:1219 regions 1213:1219 The glycosylation sites that were identified existed within regions of low complexity, rich in serine, alanine, and proline. 24673753 4 21 link meningitides-derived 690:709 arg1 protein 720:726 a Neisseria meningitides-derived acceptor protein 678:726 a Neisseria meningitides-derived acceptor protein in an Escherichia coli background 678:760 The PglLBc O-oligosaccharyltransferase (O-OTase), encoded by the cloned gene bcal0960, was shown to be capable of transferring a heptasaccharide from the Campylobacter jejuni N-glycosylation system to a Neisseria meningitides-derived acceptor protein in an Escherichia coli background, indicating that the enzyme has relaxed specificities for both the sugar donor and protein acceptor. 24673753 4 22 dep donor 835:839 arg1 the 825:827 the 825:827 the 825:827 The PglLBc O-oligosaccharyltransferase (O-OTase), encoded by the cloned gene bcal0960, was shown to be capable of transferring a heptasaccharide from the Campylobacter jejuni N-glycosylation system to a Neisseria meningitides-derived acceptor protein in an Escherichia coli background, indicating that the enzyme has relaxed specificities for both the sugar donor and protein acceptor. 24673753 9 23 theme post-translational 1484:1501 arg1 modification 1503:1514 post-translational modification 1484:1514 post-translational modification 1484:1514 This study demonstrates the first example of post-translational modification in Bcc with implications for pathogenesis. 24673753 0 24 theme general 2:8 arg1 system 34:39 A general protein O-glycosylation system 0:39 A general protein O-glycosylation system within the Burkholderia cepacia complex 0:79 A general protein O-glycosylation system within the Burkholderia cepacia complex is involved in motility and virulence. 24673753 3 25 from system 445:450 arg1 B. cenocepacia K56-2 455:474 B. cenocepacia K56-2 455:474 B. cenocepacia K56-2 455:474 In this study, we characterized a general O-linked protein glycosylation system in B. cenocepacia K56-2. 24673753 2 26 theme cystic 290:295 arg1 CF 307:308 CF 307:308 CF 307:308 Burkholderia cenocepacia is one of the most common Bcc species infecting cystic fibrosis (CF) patients and its carriage is associated with poor prognosis. 24673753 2 26 theme cystic 290:295 arg1 fibrosis 297:304 cystic fibrosis 290:304 cystic fibrosis (CF) patients 290:318 Burkholderia cenocepacia is one of the most common Bcc species infecting cystic fibrosis (CF) patients and its carriage is associated with poor prognosis. 24673753 4 27 theme jejuni N-glycosylation 645:666 arg1 system 668:673 the Campylobacter jejuni N-glycosylation system 627:673 the Campylobacter jejuni N-glycosylation system 627:673 The PglLBc O-oligosaccharyltransferase (O-OTase), encoded by the cloned gene bcal0960, was shown to be capable of transferring a heptasaccharide from the Campylobacter jejuni N-glycosylation system to a Neisseria meningitides-derived acceptor protein in an Escherichia coli background, indicating that the enzyme has relaxed specificities for both the sugar donor and protein acceptor. 24673753 6 28 theme Mass 986:989 arg1 analysis 1004:1011 Mass spectrometry analysis 986:1011 Mass spectrometry analysis 986:1011 Mass spectrometry analysis revealed that these proteins are modified with a trisaccharide HexNAc-HexNAc-Hex, which is unrelated to the O-antigen biosynthetic process. 24673753 4 29 theme protein 845:851 arg1 acceptor 853:860 protein acceptor 845:860 protein acceptor 845:860 The PglLBc O-oligosaccharyltransferase (O-OTase), encoded by the cloned gene bcal0960, was shown to be capable of transferring a heptasaccharide from the Campylobacter jejuni N-glycosylation system to a Neisseria meningitides-derived acceptor protein in an Escherichia coli background, indicating that the enzyme has relaxed specificities for both the sugar donor and protein acceptor. 24673753 4 30 theme Campylobacter 631:643 arg1 system 668:673 the Campylobacter jejuni N-glycosylation system 627:673 the Campylobacter jejuni N-glycosylation system 627:673 The PglLBc O-oligosaccharyltransferase (O-OTase), encoded by the cloned gene bcal0960, was shown to be capable of transferring a heptasaccharide from the Campylobacter jejuni N-glycosylation system to a Neisseria meningitides-derived acceptor protein in an Escherichia coli background, indicating that the enzyme has relaxed specificities for both the sugar donor and protein acceptor. 24673753 0 31 theme O-glycosylation 18:32 arg1 system 34:39 A general protein O-glycosylation system 0:39 A general protein O-glycosylation system within the Burkholderia cepacia complex 0:79 A general protein O-glycosylation system within the Burkholderia cepacia complex is involved in motility and virulence. 24673753 5 32 gly glycosylation 917:929 arg1 proteins 937:944 23 proteins 934:944 23 proteins involved in diverse cellular processes 934:983 In B cenocepacia K56-2, PglLBc is responsible for the glycosylation of 23 proteins involved in diverse cellular processes. 24673753 8 33 dep both 1400:1403 arg1 plant 1405:1409 plant 1405:1409 plant 1405:1409 Disruption of bcal0960 abolished glycosylation and resulted in reduced swimming motility and attenuated virulence towards both plant and insect model organisms. 24673753 2 34 theme species 272:278 arg1 species 272:278 the most common Bcc species 252:278 the most common Bcc species infecting cystic fibrosis (CF) patients 252:318 Burkholderia cenocepacia is one of the most common Bcc species infecting cystic fibrosis (CF) patients and its carriage is associated with poor prognosis. 24673753 2 34 theme species 272:278 arg1 one 245:247 one 245:247 one 245:247 Burkholderia cenocepacia is one of the most common Bcc species infecting cystic fibrosis (CF) patients and its carriage is associated with poor prognosis. 24673753 3 35 theme O-linked 414:421 arg1 system 445:450 a general O-linked protein glycosylation system 404:450 a general O-linked protein glycosylation system in B. cenocepacia K56-2 404:474 In this study, we characterized a general O-linked protein glycosylation system in B. cenocepacia K56-2. 24673753 0 36 theme protein 10:16 arg1 system 34:39 A general protein O-glycosylation system 0:39 A general protein O-glycosylation system within the Burkholderia cepacia complex 0:79 A general protein O-glycosylation system within the Burkholderia cepacia complex is involved in motility and virulence. 24673753 4 37 theme cloned 542:547 arg1 bcal0960 554:561 the cloned gene bcal0960 538:561 the cloned gene bcal0960 538:561 The PglLBc O-oligosaccharyltransferase (O-OTase), encoded by the cloned gene bcal0960, was shown to be capable of transferring a heptasaccharide from the Campylobacter jejuni N-glycosylation system to a Neisseria meningitides-derived acceptor protein in an Escherichia coli background, indicating that the enzyme has relaxed specificities for both the sugar donor and protein acceptor. 24673753 7 38 from alanine 1256:1262 arg1 rich 1240:1243 rich 1240:1243 rich 1240:1243 The glycosylation sites that were identified existed within regions of low complexity, rich in serine, alanine, and proline. 24673753 2 39 theme Bcc 268:270 arg1 species 272:278 the most common Bcc species 252:278 the most common Bcc species infecting cystic fibrosis (CF) patients 252:318 Burkholderia cenocepacia is one of the most common Bcc species infecting cystic fibrosis (CF) patients and its carriage is associated with poor prognosis. 24673753 1 40 theme humans 188:193 arg1 pathogens 175:183 pathogens 175:183 pathogens of humans, plants, and animals 175:214 Bacteria of the Burkholderia cepacia complex (Bcc) are pathogens of humans, plants, and animals. 24673753 1 40 theme humans 188:193 arg1 Bacteria 120:127 Bacteria 120:127 Bacteria of the Burkholderia cepacia complex (Bcc) 120:169 Bacteria of the Burkholderia cepacia complex (Bcc) are pathogens of humans, plants, and animals. 24673753 9 41 from example 1473:1479 arg1 Bcc 1519:1521 Bcc 1519:1521 Bcc 1519:1521 This study demonstrates the first example of post-translational modification in Bcc with implications for pathogenesis. 24673753 8 42 theme swimming 1349:1356 arg1 motility 1358:1365 reduced swimming motility 1341:1365 reduced swimming motility 1341:1365 Disruption of bcal0960 abolished glycosylation and resulted in reduced swimming motility and attenuated virulence towards both plant and insect model organisms. 24673753 6 43 mod modified 1046:1053 arg1 proteins 1033:1040 these proteins 1027:1040 these proteins 1027:1040 Mass spectrometry analysis revealed that these proteins are modified with a trisaccharide HexNAc-HexNAc-Hex, which is unrelated to the O-antigen biosynthetic process. 24673753 6 43 mod modified 1046:1053 arg3 HexNAc-HexNAc-Hex 1076:1092 a trisaccharide HexNAc-HexNAc-Hex 1060:1092 a trisaccharide HexNAc-HexNAc-Hex 1060:1092 Mass spectrometry analysis revealed that these proteins are modified with a trisaccharide HexNAc-HexNAc-Hex, which is unrelated to the O-antigen biosynthetic process. 24673753 6 43 mod modified 1046:1053 arg3 unrelated 1104:1112 unrelated 1104:1112 unrelated 1104:1112 Mass spectrometry analysis revealed that these proteins are modified with a trisaccharide HexNAc-HexNAc-Hex, which is unrelated to the O-antigen biosynthetic process. 24673753 1 44 theme plants 196:201 arg1 pathogens 175:183 pathogens 175:183 pathogens of humans, plants, and animals 175:214 Bacteria of the Burkholderia cepacia complex (Bcc) are pathogens of humans, plants, and animals. 24673753 1 44 theme plants 196:201 arg1 Bacteria 120:127 Bacteria 120:127 Bacteria of the Burkholderia cepacia complex (Bcc) 120:169 Bacteria of the Burkholderia cepacia complex (Bcc) are pathogens of humans, plants, and animals. 24673753 0 45 theme Burkholderia 52:63 arg1 complex 73:79 the Burkholderia cepacia complex 48:79 the Burkholderia cepacia complex 48:79 A general protein O-glycosylation system within the Burkholderia cepacia complex is involved in motility and virulence. 24673753 7 46 from rich 1240:1243 arg1 proline 1269:1275 proline 1269:1275 proline 1269:1275 The glycosylation sites that were identified existed within regions of low complexity, rich in serine, alanine, and proline. 24673753 7 46 from rich 1240:1243 arg1 serine 1248:1253 serine 1248:1253 serine 1248:1253 The glycosylation sites that were identified existed within regions of low complexity, rich in serine, alanine, and proline. 24673753 7 46 from rich 1240:1243 arg1 alanine 1256:1262 alanine 1256:1262 alanine 1256:1262 The glycosylation sites that were identified existed within regions of low complexity, rich in serine, alanine, and proline. 24673753 4 47 theme sugar 829:833 arg1 donor 835:839 sugar donor 829:839 sugar donor 829:839 The PglLBc O-oligosaccharyltransferase (O-OTase), encoded by the cloned gene bcal0960, was shown to be capable of transferring a heptasaccharide from the Campylobacter jejuni N-glycosylation system to a Neisseria meningitides-derived acceptor protein in an Escherichia coli background, indicating that the enzyme has relaxed specificities for both the sugar donor and protein acceptor. 24673753 6 48 theme biosynthetic 1131:1142 arg1 process 1144:1150 the O-antigen biosynthetic process 1117:1150 the O-antigen biosynthetic process 1117:1150 Mass spectrometry analysis revealed that these proteins are modified with a trisaccharide HexNAc-HexNAc-Hex, which is unrelated to the O-antigen biosynthetic process. 24673753 4 49 theme acceptor 711:718 arg1 protein 720:726 a Neisseria meningitides-derived acceptor protein 678:726 a Neisseria meningitides-derived acceptor protein in an Escherichia coli background 678:760 The PglLBc O-oligosaccharyltransferase (O-OTase), encoded by the cloned gene bcal0960, was shown to be capable of transferring a heptasaccharide from the Campylobacter jejuni N-glycosylation system to a Neisseria meningitides-derived acceptor protein in an Escherichia coli background, indicating that the enzyme has relaxed specificities for both the sugar donor and protein acceptor. 24673753 7 50 theme rich 1240:1243 arg1 regions 1213:1219 regions 1213:1219 regions 1213:1219 The glycosylation sites that were identified existed within regions of low complexity, rich in serine, alanine, and proline. 24673753 4 51 theme meningitides-derived 690:709 arg1 protein 720:726 a Neisseria meningitides-derived acceptor protein 678:726 a Neisseria meningitides-derived acceptor protein in an Escherichia coli background 678:760 The PglLBc O-oligosaccharyltransferase (O-OTase), encoded by the cloned gene bcal0960, was shown to be capable of transferring a heptasaccharide from the Campylobacter jejuni N-glycosylation system to a Neisseria meningitides-derived acceptor protein in an Escherichia coli background, indicating that the enzyme has relaxed specificities for both the sugar donor and protein acceptor. 24673753 4 52 theme relaxed 794:800 arg1 specificities 802:814 relaxed specificities 794:814 relaxed specificities for both the sugar donor and protein acceptor 794:860 The PglLBc O-oligosaccharyltransferase (O-OTase), encoded by the cloned gene bcal0960, was shown to be capable of transferring a heptasaccharide from the Campylobacter jejuni N-glycosylation system to a Neisseria meningitides-derived acceptor protein in an Escherichia coli background, indicating that the enzyme has relaxed specificities for both the sugar donor and protein acceptor. 24673753 5 53 theme proteins 937:944 arg1 glycosylation 917:929 the glycosylation 913:929 the glycosylation of 23 proteins involved in diverse cellular processes 913:983 In B cenocepacia K56-2, PglLBc is responsible for the glycosylation of 23 proteins involved in diverse cellular processes. 24673753 7 54 from serine 1248:1253 arg1 rich 1240:1243 rich 1240:1243 rich 1240:1243 The glycosylation sites that were identified existed within regions of low complexity, rich in serine, alanine, and proline. 24673753 3 55 theme glycosylation 431:443 arg1 system 445:450 a general O-linked protein glycosylation system 404:450 a general O-linked protein glycosylation system in B. cenocepacia K56-2 404:474 In this study, we characterized a general O-linked protein glycosylation system in B. cenocepacia K56-2. 24673753 1 56 dep Burkholderia 136:147 arg1 cepacia 149:155 cepacia 149:155 cepacia 149:155 Bacteria of the Burkholderia cepacia complex (Bcc) are pathogens of humans, plants, and animals. 24673753 8 57 theme bcal0960 1292:1299 arg1 Disruption 1278:1287 Disruption 1278:1287 Disruption of bcal0960 1278:1299 Disruption of bcal0960 abolished glycosylation and resulted in reduced swimming motility and attenuated virulence towards both plant and insect model organisms. 24673753 5 58 theme cellular 966:973 arg1 processes 975:983 diverse cellular processes 958:983 diverse cellular processes 958:983 In B cenocepacia K56-2, PglLBc is responsible for the glycosylation of 23 proteins involved in diverse cellular processes. 24673753 5 59 from B cenocepacia K56-2 866:884 arg1 responsible 897:907 responsible 897:907 responsible 897:907 In B cenocepacia K56-2, PglLBc is responsible for the glycosylation of 23 proteins involved in diverse cellular processes. 24673753 2 60 theme fibrosis 297:304 arg1 patients 311:318 cystic fibrosis (CF) patients 290:318 cystic fibrosis (CF) patients 290:318 Burkholderia cenocepacia is one of the most common Bcc species infecting cystic fibrosis (CF) patients and its carriage is associated with poor prognosis. 24673753 4 61 dep Escherichia 734:744 arg1 coli 746:749 coli 746:749 coli 746:749 The PglLBc O-oligosaccharyltransferase (O-OTase), encoded by the cloned gene bcal0960, was shown to be capable of transferring a heptasaccharide from the Campylobacter jejuni N-glycosylation system to a Neisseria meningitides-derived acceptor protein in an Escherichia coli background, indicating that the enzyme has relaxed specificities for both the sugar donor and protein acceptor. 24673753 3 62 theme general 406:412 arg1 system 445:450 a general O-linked protein glycosylation system 404:450 a general O-linked protein glycosylation system in B. cenocepacia K56-2 404:474 In this study, we characterized a general O-linked protein glycosylation system in B. cenocepacia K56-2. 24673753 7 63 gly glycosylation 1157:1169 arg2 sites 1171:1175 The glycosylation sites 1153:1175 The glycosylation sites that were identified 1153:1196 The glycosylation sites that were identified existed within regions of low complexity, rich in serine, alanine, and proline. 24673753 1 64 theme Burkholderia 136:147 arg1 Bcc 166:168 Bcc 166:168 Bcc 166:168 Bacteria of the Burkholderia cepacia complex (Bcc) are pathogens of humans, plants, and animals. 24673753 1 64 theme Burkholderia 136:147 arg1 complex 157:163 the Burkholderia cepacia complex 132:163 the Burkholderia cepacia complex (Bcc) 132:169 Bacteria of the Burkholderia cepacia complex (Bcc) are pathogens of humans, plants, and animals. 24673753 4 65 from protein 720:726 arg1 background 751:760 an Escherichia coli background 731:760 an Escherichia coli background 731:760 The PglLBc O-oligosaccharyltransferase (O-OTase), encoded by the cloned gene bcal0960, was shown to be capable of transferring a heptasaccharide from the Campylobacter jejuni N-glycosylation system to a Neisseria meningitides-derived acceptor protein in an Escherichia coli background, indicating that the enzyme has relaxed specificities for both the sugar donor and protein acceptor. 24673753 1 66 theme animals 208:214 arg1 pathogens 175:183 pathogens 175:183 pathogens of humans, plants, and animals 175:214 Bacteria of the Burkholderia cepacia complex (Bcc) are pathogens of humans, plants, and animals. 24673753 1 66 theme animals 208:214 arg1 Bacteria 120:127 Bacteria 120:127 Bacteria of the Burkholderia cepacia complex (Bcc) 120:169 Bacteria of the Burkholderia cepacia complex (Bcc) are pathogens of humans, plants, and animals. 24673753 0 67 theme cepacia 65:71 arg1 complex 73:79 the Burkholderia cepacia complex 48:79 the Burkholderia cepacia complex 48:79 A general protein O-glycosylation system within the Burkholderia cepacia complex is involved in motility and virulence. 24673753 9 68 theme modification 1503:1514 arg1 example 1473:1479 the first example 1463:1479 the first example of post-translational modification in Bcc 1463:1521 This study demonstrates the first example of post-translational modification in Bcc with implications for pathogenesis. 24673753 2 69 theme Burkholderia 217:228 arg1 cenocepacia 230:240 Burkholderia cenocepacia 217:240 Burkholderia cenocepacia 217:240 Burkholderia cenocepacia is one of the most common Bcc species infecting cystic fibrosis (CF) patients and its carriage is associated with poor prognosis. 24673753 6 70 theme O-antigen 1121:1129 arg1 process 1144:1150 the O-antigen biosynthetic process 1117:1150 the O-antigen biosynthetic process 1117:1150 Mass spectrometry analysis revealed that these proteins are modified with a trisaccharide HexNAc-HexNAc-Hex, which is unrelated to the O-antigen biosynthetic process. 24673753 4 71 contain has 790:792 arg1 enzyme 783:788 the enzyme 779:788 the enzyme 779:788 The PglLBc O-oligosaccharyltransferase (O-OTase), encoded by the cloned gene bcal0960, was shown to be capable of transferring a heptasaccharide from the Campylobacter jejuni N-glycosylation system to a Neisseria meningitides-derived acceptor protein in an Escherichia coli background, indicating that the enzyme has relaxed specificities for both the sugar donor and protein acceptor. 24673753 4 71 contain has 790:792 arg2 specificities 802:814 relaxed specificities 794:814 relaxed specificities for both the sugar donor and protein acceptor 794:860 The PglLBc O-oligosaccharyltransferase (O-OTase), encoded by the cloned gene bcal0960, was shown to be capable of transferring a heptasaccharide from the Campylobacter jejuni N-glycosylation system to a Neisseria meningitides-derived acceptor protein in an Escherichia coli background, indicating that the enzyme has relaxed specificities for both the sugar donor and protein acceptor. 24946017 5 0 theme statistical 657:667 arg1 method 669:674 a novel statistical method 649:674 a novel statistical method to quantify the site-specific glycosylation of glycoproteins in complex samples using label-free mass spectrometric techniques 649:801 Here we present a novel statistical method to quantify the site-specific glycosylation of glycoproteins in complex samples using label-free mass spectrometric techniques. 24946017 6 1 theme same 952:955 arg1 site 957:960 the same site 948:960 the same site 948:960 Abundance variations between sites of a glycoprotein as well as different glycoforms, that is, glycopeptides with different glycans attached to the same site, can be detected using these techniques. 24946017 8 2 theme site-specific 1266:1278 arg1 glycosylations 1280:1293 significantly different site-specific glycosylations 1242:1293 significantly different site-specific glycosylations 1242:1293 A few glycoproteins, including vitronectin, showed significantly different site-specific glycosylations within cancer/control samples, indicating that our method is ready to be used for the discovery of glycosylated biomarkers. 24946017 1 3 theme immune 166:171 arg1 response 173:180 immune response 166:180 immune response 166:180 Glycan moieties of glycoproteins modulate many biological processes in mammals, such as immune response, inflammation, and cell signaling. 24946017 1 4 gly glycoproteins 97:109 arg1 glycoproteins 97:109 glycoproteins 97:109 glycoproteins 97:109 Glycan moieties of glycoproteins modulate many biological processes in mammals, such as immune response, inflammation, and cell signaling. 24946017 0 5 dep quantification 24:37 arg1 discovery 53:61 biomarker discovery 43:61 biomarker discovery in human sera 43:75 Label-free glycopeptide quantification for biomarker discovery in human sera. 24946017 8 6 theme glycosylated 1394:1405 arg1 biomarkers 1407:1416 glycosylated biomarkers 1394:1416 glycosylated biomarkers 1394:1416 A few glycoproteins, including vitronectin, showed significantly different site-specific glycosylations within cancer/control samples, indicating that our method is ready to be used for the discovery of glycosylated biomarkers. 24946017 8 7 theme few 1193:1195 arg1 glycoproteins 1197:1209 A few glycoproteins 1191:1209 A few glycoproteins 1191:1209 A few glycoproteins, including vitronectin, showed significantly different site-specific glycosylations within cancer/control samples, indicating that our method is ready to be used for the discovery of glycosylated biomarkers. 24946017 8 7 theme few 1193:1195 arg1 vitronectin 1222:1232 vitronectin 1222:1232 vitronectin 1222:1232 A few glycoproteins, including vitronectin, showed significantly different site-specific glycosylations within cancer/control samples, indicating that our method is ready to be used for the discovery of glycosylated biomarkers. 24946017 5 8 theme label-free 762:771 arg1 techniques 792:801 label-free mass spectrometric techniques 762:801 label-free mass spectrometric techniques 762:801 Here we present a novel statistical method to quantify the site-specific glycosylation of glycoproteins in complex samples using label-free mass spectrometric techniques. 24946017 7 9 theme potential 1129:1137 arg1 biomarkers 1139:1148 potential biomarkers 1129:1148 potential biomarkers of site-specific N-linked glycosylation 1129:1188 We applied our method to an esophageal cancer study based on blood serum samples from cancer patients in an attempt to detect potential biomarkers of site-specific N-linked glycosylation. 24946017 2 10 theme quantitative 284:295 arg1 alteration 297:306 quantitative alteration 284:306 quantitative alteration of protein glycosylation 284:331 Numerous studies show that many human diseases are correlated with quantitative alteration of protein glycosylation. 24946017 7 11 from patients 1096:1103 arg1 attempt 1111:1117 an attempt to detect potential biomarkers of site-specific N-linked glycosylation 1108:1188 an attempt to detect potential biomarkers of site-specific N-linked glycosylation 1108:1188 We applied our method to an esophageal cancer study based on blood serum samples from cancer patients in an attempt to detect potential biomarkers of site-specific N-linked glycosylation. 24946017 7 11 from patients 1096:1103 arg1 samples 1076:1082 blood serum samples 1064:1082 blood serum samples from cancer patients in an attempt to detect potential biomarkers of site-specific N-linked glycosylation 1064:1188 We applied our method to an esophageal cancer study based on blood serum samples from cancer patients in an attempt to detect potential biomarkers of site-specific N-linked glycosylation. 24946017 5 12 theme mass 773:776 arg1 techniques 792:801 label-free mass spectrometric techniques 762:801 label-free mass spectrometric techniques 762:801 Here we present a novel statistical method to quantify the site-specific glycosylation of glycoproteins in complex samples using label-free mass spectrometric techniques. 24946017 3 13 theme global 459:464 arg1 abundance 466:474 the global abundance 455:474 the global abundance of the glycoprotein 455:494 In some cases, these changes can occur for certain types of glycans over specific sites in a glycoprotein rather than on the global abundance of the glycoprotein. 24946017 1 14 theme Glycan 78:83 arg1 moieties 85:92 Glycan moieties 78:92 Glycan moieties of glycoproteins 78:109 Glycan moieties of glycoproteins modulate many biological processes in mammals, such as immune response, inflammation, and cell signaling. 24946017 6 15 attach attached 936:943 arg1 site 957:960 the same site 948:960 the same site 948:960 Abundance variations between sites of a glycoprotein as well as different glycoforms, that is, glycopeptides with different glycans attached to the same site, can be detected using these techniques. 24946017 6 15 attach attached 936:943 arg2 glycans 928:934 different glycans 918:934 different glycans attached to the same site 918:960 Abundance variations between sites of a glycoprotein as well as different glycoforms, that is, glycopeptides with different glycans attached to the same site, can be detected using these techniques. 24946017 5 16 theme spectrometric 778:790 arg1 techniques 792:801 label-free mass spectrometric techniques 762:801 label-free mass spectrometric techniques 762:801 Here we present a novel statistical method to quantify the site-specific glycosylation of glycoproteins in complex samples using label-free mass spectrometric techniques. 24946017 0 17 from discovery 53:61 arg1 sera 72:75 human sera 66:75 human sera 66:75 Label-free glycopeptide quantification for biomarker discovery in human sera. 24946017 7 18 theme glycosylation 1176:1188 arg1 biomarkers 1139:1148 potential biomarkers 1129:1148 potential biomarkers of site-specific N-linked glycosylation 1129:1188 We applied our method to an esophageal cancer study based on blood serum samples from cancer patients in an attempt to detect potential biomarkers of site-specific N-linked glycosylation. 24946017 4 19 gly glycoproteins 583:595 arg1 glycoproteins 583:595 glycoproteins 583:595 glycoproteins 583:595 Conventional analytical techniques that analyze the abundance of glycans cleaved from glycoproteins cannot reveal these subtle effects. 24946017 8 20 theme biomarkers 1407:1416 arg1 discovery 1381:1389 the discovery 1377:1389 the discovery of glycosylated biomarkers 1377:1416 A few glycoproteins, including vitronectin, showed significantly different site-specific glycosylations within cancer/control samples, indicating that our method is ready to be used for the discovery of glycosylated biomarkers. 24946017 0 21 theme glycopeptide 11:22 arg1 quantification 24:37 Label-free glycopeptide quantification 0:37 Label-free glycopeptide quantification 0:37 Label-free glycopeptide quantification for biomarker discovery in human sera. 24946017 6 22 theme different 918:926 arg1 glycans 928:934 different glycans 918:934 different glycans attached to the same site 918:960 Abundance variations between sites of a glycoprotein as well as different glycoforms, that is, glycopeptides with different glycans attached to the same site, can be detected using these techniques. 24946017 5 23 gly glycosylation 706:718 arg1 glycoproteins 723:735 glycoproteins 723:735 glycoproteins 723:735 Here we present a novel statistical method to quantify the site-specific glycosylation of glycoproteins in complex samples using label-free mass spectrometric techniques. 24946017 5 23 gly glycosylation 706:718 arg1 samples 748:754 complex samples 740:754 complex samples using label-free mass spectrometric techniques 740:801 Here we present a novel statistical method to quantify the site-specific glycosylation of glycoproteins in complex samples using label-free mass spectrometric techniques. 24946017 8 24 theme different 1256:1264 arg1 glycosylations 1280:1293 significantly different site-specific glycosylations 1242:1293 significantly different site-specific glycosylations 1242:1293 A few glycoproteins, including vitronectin, showed significantly different site-specific glycosylations within cancer/control samples, indicating that our method is ready to be used for the discovery of glycosylated biomarkers. 24946017 3 25 gly glycoprotein 483:494 arg1 glycoprotein 483:494 the glycoprotein 479:494 the glycoprotein 479:494 In some cases, these changes can occur for certain types of glycans over specific sites in a glycoprotein rather than on the global abundance of the glycoprotein. 24946017 7 26 theme serum 1070:1074 arg1 samples 1076:1082 blood serum samples 1064:1082 blood serum samples from cancer patients in an attempt to detect potential biomarkers of site-specific N-linked glycosylation 1064:1188 We applied our method to an esophageal cancer study based on blood serum samples from cancer patients in an attempt to detect potential biomarkers of site-specific N-linked glycosylation. 24946017 3 27 theme certain 377:383 arg1 types 385:389 certain types 377:389 certain types of glycans 377:400 In some cases, these changes can occur for certain types of glycans over specific sites in a glycoprotein rather than on the global abundance of the glycoprotein. 24946017 0 28 theme Label-free 0:9 arg1 quantification 24:37 Label-free glycopeptide quantification 0:37 Label-free glycopeptide quantification 0:37 Label-free glycopeptide quantification for biomarker discovery in human sera. 24946017 4 29 theme glycans 562:568 arg1 abundance 549:557 the abundance 545:557 the abundance of glycans cleaved from glycoproteins 545:595 Conventional analytical techniques that analyze the abundance of glycans cleaved from glycoproteins cannot reveal these subtle effects. 24946017 5 30 theme novel 651:655 arg1 method 669:674 a novel statistical method 649:674 a novel statistical method to quantify the site-specific glycosylation of glycoproteins in complex samples using label-free mass spectrometric techniques 649:801 Here we present a novel statistical method to quantify the site-specific glycosylation of glycoproteins in complex samples using label-free mass spectrometric techniques. 24946017 1 31 theme glycoproteins 97:109 arg1 moieties 85:92 Glycan moieties 78:92 Glycan moieties of glycoproteins 78:109 Glycan moieties of glycoproteins modulate many biological processes in mammals, such as immune response, inflammation, and cell signaling. 24946017 6 32 gly glycopeptides 899:911 arg2 glycopeptides 899:911 glycopeptides 899:911 glycopeptides with different glycans attached to the same site 899:960 Abundance variations between sites of a glycoprotein as well as different glycoforms, that is, glycopeptides with different glycans attached to the same site, can be detected using these techniques. 24946017 6 32 gly glycopeptides 899:911 arg2 glycoforms 878:887 different glycoforms 868:887 different glycoforms 868:887 Abundance variations between sites of a glycoprotein as well as different glycoforms, that is, glycopeptides with different glycans attached to the same site, can be detected using these techniques. 24946017 6 33 with glycopeptides 899:911 arg1 glycans 928:934 different glycans 918:934 different glycans attached to the same site 918:960 Abundance variations between sites of a glycoprotein as well as different glycoforms, that is, glycopeptides with different glycans attached to the same site, can be detected using these techniques. 24946017 8 34 gly glycosylated 1394:1405 arg1 biomarkers 1407:1416 glycosylated biomarkers 1394:1416 glycosylated biomarkers 1394:1416 A few glycoproteins, including vitronectin, showed significantly different site-specific glycosylations within cancer/control samples, indicating that our method is ready to be used for the discovery of glycosylated biomarkers. 24946017 5 35 theme glycoproteins 723:735 arg1 glycosylation 706:718 the site-specific glycosylation 688:718 the site-specific glycosylation of glycoproteins in complex samples using label-free mass spectrometric techniques 688:801 Here we present a novel statistical method to quantify the site-specific glycosylation of glycoproteins in complex samples using label-free mass spectrometric techniques. 24946017 6 36 theme glycoprotein 844:855 arg1 sites 833:837 sites 833:837 sites of a glycoprotein 833:855 Abundance variations between sites of a glycoprotein as well as different glycoforms, that is, glycopeptides with different glycans attached to the same site, can be detected using these techniques. 24946017 6 36 theme glycoprotein 844:855 arg1 glycoprotein 844:855 a glycoprotein 842:855 a glycoprotein 842:855 Abundance variations between sites of a glycoprotein as well as different glycoforms, that is, glycopeptides with different glycans attached to the same site, can be detected using these techniques. 24946017 2 37 theme protein 311:317 arg1 glycosylation 319:331 protein glycosylation 311:331 protein glycosylation 311:331 Numerous studies show that many human diseases are correlated with quantitative alteration of protein glycosylation. 24946017 2 38 theme glycosylation 319:331 arg1 alteration 297:306 quantitative alteration 284:306 quantitative alteration of protein glycosylation 284:331 Numerous studies show that many human diseases are correlated with quantitative alteration of protein glycosylation. 24946017 1 39 theme many 120:123 arg1 processes 136:144 many biological processes 120:144 many biological processes 120:144 Glycan moieties of glycoproteins modulate many biological processes in mammals, such as immune response, inflammation, and cell signaling. 24946017 1 40 theme cell 201:204 arg1 signaling 206:214 cell signaling 201:214 cell signaling 201:214 Glycan moieties of glycoproteins modulate many biological processes in mammals, such as immune response, inflammation, and cell signaling. 24946017 3 41 theme specific 407:414 arg1 sites 416:420 specific sites 407:420 specific sites in a glycoprotein rather than on the global abundance of the glycoprotein 407:494 In some cases, these changes can occur for certain types of glycans over specific sites in a glycoprotein rather than on the global abundance of the glycoprotein. 24946017 5 42 gly glycoproteins 723:735 arg1 glycoproteins 723:735 glycoproteins 723:735 glycoproteins 723:735 Here we present a novel statistical method to quantify the site-specific glycosylation of glycoproteins in complex samples using label-free mass spectrometric techniques. 24946017 5 43 theme complex 740:746 arg1 samples 748:754 complex samples 740:754 complex samples using label-free mass spectrometric techniques 740:801 Here we present a novel statistical method to quantify the site-specific glycosylation of glycoproteins in complex samples using label-free mass spectrometric techniques. 24946017 8 44 used used 1368:1371 arg2 method 1346:1351 our method 1342:1351 our method 1342:1351 A few glycoproteins, including vitronectin, showed significantly different site-specific glycosylations within cancer/control samples, indicating that our method is ready to be used for the discovery of glycosylated biomarkers. 24946017 7 45 theme site-specific 1153:1165 arg1 glycosylation 1176:1188 site-specific N-linked glycosylation 1153:1188 site-specific N-linked glycosylation 1153:1188 We applied our method to an esophageal cancer study based on blood serum samples from cancer patients in an attempt to detect potential biomarkers of site-specific N-linked glycosylation. 24946017 0 46 theme biomarker 43:51 arg1 discovery 53:61 biomarker discovery 43:61 biomarker discovery in human sera 43:75 Label-free glycopeptide quantification for biomarker discovery in human sera. 24946017 0 47 gly glycopeptide 11:22 arg2 glycopeptide 11:22 Label-free glycopeptide quantification 0:37 Label-free glycopeptide quantification 0:37 Label-free glycopeptide quantification for biomarker discovery in human sera. 24946017 7 48 theme cancer 1042:1047 arg1 study 1049:1053 an esophageal cancer study 1028:1053 an esophageal cancer study based on blood serum samples from cancer patients in an attempt to detect potential biomarkers of site-specific N-linked glycosylation 1028:1188 We applied our method to an esophageal cancer study based on blood serum samples from cancer patients in an attempt to detect potential biomarkers of site-specific N-linked glycosylation. 24946017 0 49 theme human 66:70 arg1 sera 72:75 human sera 66:75 human sera 66:75 Label-free glycopeptide quantification for biomarker discovery in human sera. 24946017 7 50 theme cancer 1089:1094 arg1 patients 1096:1103 cancer patients 1089:1103 cancer patients in an attempt to detect potential biomarkers of site-specific N-linked glycosylation 1089:1188 We applied our method to an esophageal cancer study based on blood serum samples from cancer patients in an attempt to detect potential biomarkers of site-specific N-linked glycosylation. 24946017 7 51 theme blood 1064:1068 arg1 samples 1076:1082 blood serum samples 1064:1082 blood serum samples from cancer patients in an attempt to detect potential biomarkers of site-specific N-linked glycosylation 1064:1188 We applied our method to an esophageal cancer study based on blood serum samples from cancer patients in an attempt to detect potential biomarkers of site-specific N-linked glycosylation. 24946017 6 52 theme Abundance 804:812 arg1 variations 814:823 Abundance variations 804:823 Abundance variations between sites of a glycoprotein as well as different glycoforms, that is, glycopeptides with different glycans attached to the same site, 804:961 Abundance variations between sites of a glycoprotein as well as different glycoforms, that is, glycopeptides with different glycans attached to the same site, can be detected using these techniques. 24946017 1 53 theme biological 125:134 arg1 processes 136:144 many biological processes 120:144 many biological processes 120:144 Glycan moieties of glycoproteins modulate many biological processes in mammals, such as immune response, inflammation, and cell signaling. 24946017 3 54 from sites 416:420 arg1 glycoprotein 427:438 a glycoprotein 425:438 a glycoprotein rather than on the global abundance of the glycoprotein 425:494 In some cases, these changes can occur for certain types of glycans over specific sites in a glycoprotein rather than on the global abundance of the glycoprotein. 24946017 3 54 from sites 416:420 arg1 abundance 466:474 the global abundance 455:474 the global abundance of the glycoprotein 455:494 In some cases, these changes can occur for certain types of glycans over specific sites in a glycoprotein rather than on the global abundance of the glycoprotein. 24946017 6 55 gly glycoprotein 844:855 arg1 glycoprotein 844:855 a glycoprotein 842:855 a glycoprotein 842:855 Abundance variations between sites of a glycoprotein as well as different glycoforms, that is, glycopeptides with different glycans attached to the same site, can be detected using these techniques. 24946017 5 56 theme site-specific 692:704 arg1 glycosylation 706:718 the site-specific glycosylation 688:718 the site-specific glycosylation of glycoproteins in complex samples using label-free mass spectrometric techniques 688:801 Here we present a novel statistical method to quantify the site-specific glycosylation of glycoproteins in complex samples using label-free mass spectrometric techniques. 24946017 2 57 theme Numerous 217:224 arg1 studies 226:232 Numerous studies 217:232 Numerous studies 217:232 Numerous studies show that many human diseases are correlated with quantitative alteration of protein glycosylation. 24946017 3 58 theme glycoprotein 483:494 arg1 abundance 466:474 the global abundance 455:474 the global abundance of the glycoprotein 455:494 In some cases, these changes can occur for certain types of glycans over specific sites in a glycoprotein rather than on the global abundance of the glycoprotein. 24946017 7 59 theme N-linked 1167:1174 arg1 glycosylation 1176:1188 site-specific N-linked glycosylation 1153:1188 site-specific N-linked glycosylation 1153:1188 We applied our method to an esophageal cancer study based on blood serum samples from cancer patients in an attempt to detect potential biomarkers of site-specific N-linked glycosylation. 24946017 7 60 link N-linked 1167:1174 arg1 glycosylation 1176:1188 site-specific N-linked glycosylation 1153:1188 site-specific N-linked glycosylation 1153:1188 We applied our method to an esophageal cancer study based on blood serum samples from cancer patients in an attempt to detect potential biomarkers of site-specific N-linked glycosylation. 24946017 5 61 from glycosylation 706:718 arg1 samples 748:754 complex samples 740:754 complex samples using label-free mass spectrometric techniques 740:801 Here we present a novel statistical method to quantify the site-specific glycosylation of glycoproteins in complex samples using label-free mass spectrometric techniques. 24946017 7 62 theme esophageal 1031:1040 arg1 study 1049:1053 an esophageal cancer study 1028:1053 an esophageal cancer study based on blood serum samples from cancer patients in an attempt to detect potential biomarkers of site-specific N-linked glycosylation 1028:1188 We applied our method to an esophageal cancer study based on blood serum samples from cancer patients in an attempt to detect potential biomarkers of site-specific N-linked glycosylation. 24946017 4 63 theme analytical 510:519 arg1 techniques 521:530 Conventional analytical techniques 497:530 Conventional analytical techniques that analyze the abundance of glycans cleaved from glycoproteins 497:595 Conventional analytical techniques that analyze the abundance of glycans cleaved from glycoproteins cannot reveal these subtle effects. 24946017 3 64 gly glycoprotein 427:438 arg1 glycoprotein 427:438 a glycoprotein 425:438 a glycoprotein rather than on the global abundance of the glycoprotein 425:494 In some cases, these changes can occur for certain types of glycans over specific sites in a glycoprotein rather than on the global abundance of the glycoprotein. 24946017 4 65 theme subtle 617:622 arg1 effects 624:630 these subtle effects 611:630 these subtle effects 611:630 Conventional analytical techniques that analyze the abundance of glycans cleaved from glycoproteins cannot reveal these subtle effects. 24946017 6 66 theme different 868:876 arg1 glycopeptides 899:911 glycopeptides 899:911 glycopeptides with different glycans attached to the same site 899:960 Abundance variations between sites of a glycoprotein as well as different glycoforms, that is, glycopeptides with different glycans attached to the same site, can be detected using these techniques. 24946017 6 66 theme different 868:876 arg1 glycoforms 878:887 different glycoforms 868:887 different glycoforms 868:887 Abundance variations between sites of a glycoprotein as well as different glycoforms, that is, glycopeptides with different glycans attached to the same site, can be detected using these techniques. 24946017 2 67 theme human 249:253 arg1 diseases 255:262 many human diseases 244:262 many human diseases 244:262 Numerous studies show that many human diseases are correlated with quantitative alteration of protein glycosylation. 24946017 3 68 theme glycans 394:400 arg1 types 385:389 certain types 377:389 certain types of glycans 377:400 In some cases, these changes can occur for certain types of glycans over specific sites in a glycoprotein rather than on the global abundance of the glycoprotein. 24946017 4 69 theme Conventional 497:508 arg1 techniques 521:530 Conventional analytical techniques 497:530 Conventional analytical techniques that analyze the abundance of glycans cleaved from glycoproteins 497:595 Conventional analytical techniques that analyze the abundance of glycans cleaved from glycoproteins cannot reveal these subtle effects. 24946017 2 70 theme many 244:247 arg1 diseases 255:262 many human diseases 244:262 many human diseases 244:262 Numerous studies show that many human diseases are correlated with quantitative alteration of protein glycosylation. 24946017 8 71 gly glycoproteins 1197:1209 arg1 glycoproteins 1197:1209 A few glycoproteins 1191:1209 A few glycoproteins 1191:1209 A few glycoproteins, including vitronectin, showed significantly different site-specific glycosylations within cancer/control samples, indicating that our method is ready to be used for the discovery of glycosylated biomarkers. 24946017 8 71 gly glycoproteins 1197:1209 arg1 vitronectin 1222:1232 vitronectin 1222:1232 vitronectin 1222:1232 A few glycoproteins, including vitronectin, showed significantly different site-specific glycosylations within cancer/control samples, indicating that our method is ready to be used for the discovery of glycosylated biomarkers. 24946017 8 72 theme cancer/control 1302:1315 arg1 samples 1317:1323 cancer/control samples 1302:1323 cancer/control samples 1302:1323 A few glycoproteins, including vitronectin, showed significantly different site-specific glycosylations within cancer/control samples, indicating that our method is ready to be used for the discovery of glycosylated biomarkers. 29048832 7 0 theme corresponding 1477:1489 arg1 289 1504:1506 289 1504:1506 289 1504:1506 In contrast, the numbers of identified glycopeptides, glycoproteins and N-glycosylation sites identified by Cys@SiO2 were 211, 67, 127 respectively less than by Cys-Mal@SiO2, and the corresponding numbers were 289, 76, 193 by Mal@SiO2. 29048832 7 0 theme corresponding 1477:1489 arg1 numbers 1491:1497 the corresponding numbers 1473:1497 the corresponding numbers 1473:1497 In contrast, the numbers of identified glycopeptides, glycoproteins and N-glycosylation sites identified by Cys@SiO2 were 211, 67, 127 respectively less than by Cys-Mal@SiO2, and the corresponding numbers were 289, 76, 193 by Mal@SiO2. 29048832 6 1 theme unique 1099:1104 arg1 glycopeptides 1106:1118 1551 unique glycopeptides 1094:1118 1551 unique glycopeptides with 906 N-glycosylation sites from 466 different N-linked glycoproteins 1094:1191 In addition, 1551 unique glycopeptides with 906 N-glycosylation sites from 466 different N-linked glycoproteins were identified from the proteins extracted from mouse liver after the enrichment with Cys-Mal@SiO2. 29048832 3 2 gly glycopeptides 661:673 arg2 glycopeptides 661:673 N-linked glycopeptides 652:673 N-linked glycopeptides 652:673 The developed hydrophilic silica was packed into a solid phase extraction (SPE) column, and applied to the highly selective enrichment and identification of N-linked glycopeptides. 29048832 8 3 theme complex 1655:1661 arg1 samples 1674:1680 real complex biological samples 1650:1680 real complex biological samples 1650:1680 These results showed that the developed Cys-Mal@SiO2 is a promising affinity material for N-glycoproteomics research of real complex biological samples. 29048832 8 4 theme promising 1588:1596 arg1 material 1607:1614 a promising affinity material 1586:1614 a promising affinity material for N-glycoproteomics research of real complex biological samples 1586:1680 These results showed that the developed Cys-Mal@SiO2 is a promising affinity material for N-glycoproteomics research of real complex biological samples. 29048832 8 4 theme promising 1588:1596 arg1 SiO2 1578:1581 the developed Cys-Mal@SiO2 1556:1581 the developed Cys-Mal@SiO2 1556:1581 These results showed that the developed Cys-Mal@SiO2 is a promising affinity material for N-glycoproteomics research of real complex biological samples. 29048832 1 5 gly glycoprotein 185:196 arg1 glycoprotein 185:196 glycoprotein 185:196 glycoprotein 185:196 Because of the low abundance of glycoprotein and glycopeptide in complex biological samples, it is urgent to develop an efficient method for glycopeptide enrichment in comprehensive and in-depth glycoproteomes research. 29048832 8 6 theme samples 1674:1680 arg1 research 1638:1645 N-glycoproteomics research 1620:1645 N-glycoproteomics research of real complex biological samples 1620:1680 These results showed that the developed Cys-Mal@SiO2 is a promising affinity material for N-glycoproteomics research of real complex biological samples. 29048832 4 7 theme due 859:861 arg1 enrichment 848:857 glycopeptide enrichment 835:857 glycopeptide enrichment due to the synergistic effect of the two kinds of hydrophilic molecules 835:929 The Cys-Mal@SiO2 demonstrated better identification capability over Cys@SiO2, Mal@SiO2 and commercial hydrophilic interaction liquid chromatography (HILIC) in glycopeptide enrichment due to the synergistic effect of the two kinds of hydrophilic molecules. 29048832 1 8 gly glycopeptide 202:213 arg2 glycopeptide 202:213 glycopeptide 202:213 glycopeptide 202:213 Because of the low abundance of glycoprotein and glycopeptide in complex biological samples, it is urgent to develop an efficient method for glycopeptide enrichment in comprehensive and in-depth glycoproteomes research. 29048832 3 9 theme phase 552:556 arg1 column 575:580 a solid phase extraction (SPE) column 544:580 a solid phase extraction (SPE) column 544:580 The developed hydrophilic silica was packed into a solid phase extraction (SPE) column, and applied to the highly selective enrichment and identification of N-linked glycopeptides. 29048832 5 10 from G 1004:1004 arg1 enrichment 949:958 the selective enrichment 935:958 the selective enrichment of tryptic digest from human immunoglobulin G 935:1004 In the selective enrichment of tryptic digest from human immunoglobulin G, glycopeptides with higher signal-to-noises were detected by Cys-Mal@SiO2. 29048832 2 11 with modification 438:449 arg1 SiO2 488:491 Cys-Mal@SiO2 480:491 Cys-Mal@SiO2 480:491 Herein, a novel hydrophilic silica was developed through surface modification with cysteine-click maltose (Cys-Mal@SiO2). 29048832 2 11 with modification 438:449 arg1 maltose 471:477 cysteine-click maltose 456:477 cysteine-click maltose (Cys-Mal@SiO2) 456:492 Herein, a novel hydrophilic silica was developed through surface modification with cysteine-click maltose (Cys-Mal@SiO2). 29048832 4 12 theme @ 687:687 arg1 SiO2 688:691 The Cys-Mal@SiO2 676:691 The Cys-Mal@SiO2 676:691 The Cys-Mal@SiO2 demonstrated better identification capability over Cys@SiO2, Mal@SiO2 and commercial hydrophilic interaction liquid chromatography (HILIC) in glycopeptide enrichment due to the synergistic effect of the two kinds of hydrophilic molecules. 29048832 6 13 gly glycoproteins 1179:1191 arg1 glycoproteins 1179:1191 466 different N-linked glycoproteins 1156:1191 466 different N-linked glycoproteins 1156:1191 In addition, 1551 unique glycopeptides with 906 N-glycosylation sites from 466 different N-linked glycoproteins were identified from the proteins extracted from mouse liver after the enrichment with Cys-Mal@SiO2. 29048832 6 14 theme different 1160:1168 arg1 glycoproteins 1179:1191 466 different N-linked glycoproteins 1156:1191 466 different N-linked glycoproteins 1156:1191 In addition, 1551 unique glycopeptides with 906 N-glycosylation sites from 466 different N-linked glycoproteins were identified from the proteins extracted from mouse liver after the enrichment with Cys-Mal@SiO2. 29048832 1 15 theme biological 226:235 arg1 samples 237:243 complex biological samples 218:243 complex biological samples 218:243 Because of the low abundance of glycoprotein and glycopeptide in complex biological samples, it is urgent to develop an efficient method for glycopeptide enrichment in comprehensive and in-depth glycoproteomes research. 29048832 4 16 theme kinds 900:904 arg1 effect 882:887 the synergistic effect 866:887 the synergistic effect of the two kinds of hydrophilic molecules 866:929 The Cys-Mal@SiO2 demonstrated better identification capability over Cys@SiO2, Mal@SiO2 and commercial hydrophilic interaction liquid chromatography (HILIC) in glycopeptide enrichment due to the synergistic effect of the two kinds of hydrophilic molecules. 29048832 7 17 theme Cys 1402:1404 arg1 SiO2 1406:1409 Cys@SiO2 1402:1409 Cys@SiO2 1402:1409 In contrast, the numbers of identified glycopeptides, glycoproteins and N-glycosylation sites identified by Cys@SiO2 were 211, 67, 127 respectively less than by Cys-Mal@SiO2, and the corresponding numbers were 289, 76, 193 by Mal@SiO2. 29048832 1 18 gly glycopeptide 294:305 arg2 glycopeptide 294:305 glycopeptide enrichment 294:316 glycopeptide enrichment in comprehensive and in-depth glycoproteomes research 294:370 Because of the low abundance of glycoprotein and glycopeptide in complex biological samples, it is urgent to develop an efficient method for glycopeptide enrichment in comprehensive and in-depth glycoproteomes research. 29048832 0 19 gly glycopeptides 137:149 arg2 glycopeptides 137:149 glycopeptides 137:149 glycopeptides 137:149 [Preparation of cysteine-click maltose modified silica as a hydrophilic interaction liquid chromatography material for the enrichment of glycopeptides]. 29048832 4 20 theme hydrophilic 909:919 arg1 molecules 921:929 hydrophilic molecules 909:929 hydrophilic molecules 909:929 The Cys-Mal@SiO2 demonstrated better identification capability over Cys@SiO2, Mal@SiO2 and commercial hydrophilic interaction liquid chromatography (HILIC) in glycopeptide enrichment due to the synergistic effect of the two kinds of hydrophilic molecules. 29048832 6 21 theme mouse 1242:1246 arg1 liver 1248:1252 mouse liver 1242:1252 mouse liver 1242:1252 In addition, 1551 unique glycopeptides with 906 N-glycosylation sites from 466 different N-linked glycoproteins were identified from the proteins extracted from mouse liver after the enrichment with Cys-Mal@SiO2. 29048832 4 22 theme @ 747:747 arg1 SiO2 748:751 Cys@SiO2 744:751 Cys@SiO2 744:751 The Cys-Mal@SiO2 demonstrated better identification capability over Cys@SiO2, Mal@SiO2 and commercial hydrophilic interaction liquid chromatography (HILIC) in glycopeptide enrichment due to the synergistic effect of the two kinds of hydrophilic molecules. 29048832 5 23 theme @ 1074:1074 arg1 SiO2 1075:1078 Cys-Mal@SiO2 1067:1078 Cys-Mal@SiO2 1067:1078 In the selective enrichment of tryptic digest from human immunoglobulin G, glycopeptides with higher signal-to-noises were detected by Cys-Mal@SiO2. 29048832 7 24 theme N-glycosylation 1366:1380 arg1 sites 1382:1386 N-glycosylation sites 1366:1386 N-glycosylation sites 1366:1386 In contrast, the numbers of identified glycopeptides, glycoproteins and N-glycosylation sites identified by Cys@SiO2 were 211, 67, 127 respectively less than by Cys-Mal@SiO2, and the corresponding numbers were 289, 76, 193 by Mal@SiO2. 29048832 0 25 theme hydrophilic 60:70 arg1 chromatography 91:104 a hydrophilic interaction liquid chromatography 58:104 a hydrophilic interaction liquid chromatography material 58:113 [Preparation of cysteine-click maltose modified silica as a hydrophilic interaction liquid chromatography material for the enrichment of glycopeptides]. 29048832 1 26 theme in-depth 339:346 arg1 research 363:370 comprehensive and in-depth glycoproteomes research 321:370 comprehensive and in-depth glycoproteomes research 321:370 Because of the low abundance of glycoprotein and glycopeptide in complex biological samples, it is urgent to develop an efficient method for glycopeptide enrichment in comprehensive and in-depth glycoproteomes research. 29048832 4 27 gly glycopeptide 835:846 arg2 glycopeptide 835:846 glycopeptide enrichment 835:857 glycopeptide enrichment due to the synergistic effect of the two kinds of hydrophilic molecules 835:929 The Cys-Mal@SiO2 demonstrated better identification capability over Cys@SiO2, Mal@SiO2 and commercial hydrophilic interaction liquid chromatography (HILIC) in glycopeptide enrichment due to the synergistic effect of the two kinds of hydrophilic molecules. 29048832 1 28 from abundance 172:180 arg1 samples 237:243 complex biological samples 218:243 complex biological samples 218:243 Because of the low abundance of glycoprotein and glycopeptide in complex biological samples, it is urgent to develop an efficient method for glycopeptide enrichment in comprehensive and in-depth glycoproteomes research. 29048832 7 29 from 127 1425:1427 arg1 contrast 1297:1304 contrast 1297:1304 contrast 1297:1304 In contrast, the numbers of identified glycopeptides, glycoproteins and N-glycosylation sites identified by Cys@SiO2 were 211, 67, 127 respectively less than by Cys-Mal@SiO2, and the corresponding numbers were 289, 76, 193 by Mal@SiO2. 29048832 6 30 gly glycopeptides 1106:1118 arg1 glycoproteins 1179:1191 466 different N-linked glycoproteins 1156:1191 466 different N-linked glycoproteins 1156:1191 In addition, 1551 unique glycopeptides with 906 N-glycosylation sites from 466 different N-linked glycoproteins were identified from the proteins extracted from mouse liver after the enrichment with Cys-Mal@SiO2. 29048832 6 30 gly glycopeptides 1106:1118 arg2 glycopeptides 1106:1118 1551 unique glycopeptides 1094:1118 1551 unique glycopeptides with 906 N-glycosylation sites from 466 different N-linked glycoproteins 1094:1191 In addition, 1551 unique glycopeptides with 906 N-glycosylation sites from 466 different N-linked glycoproteins were identified from the proteins extracted from mouse liver after the enrichment with Cys-Mal@SiO2. 29048832 4 31 theme identification 713:726 arg1 capability 728:737 better identification capability 706:737 better identification capability 706:737 The Cys-Mal@SiO2 demonstrated better identification capability over Cys@SiO2, Mal@SiO2 and commercial hydrophilic interaction liquid chromatography (HILIC) in glycopeptide enrichment due to the synergistic effect of the two kinds of hydrophilic molecules. 29048832 0 32 theme liquid 84:89 arg1 chromatography 91:104 a hydrophilic interaction liquid chromatography 58:104 a hydrophilic interaction liquid chromatography material 58:113 [Preparation of cysteine-click maltose modified silica as a hydrophilic interaction liquid chromatography material for the enrichment of glycopeptides]. 29048832 1 33 theme low 168:170 arg1 abundance 172:180 the low abundance 164:180 the low abundance of glycoprotein and glycopeptide in complex biological samples 164:243 Because of the low abundance of glycoprotein and glycopeptide in complex biological samples, it is urgent to develop an efficient method for glycopeptide enrichment in comprehensive and in-depth glycoproteomes research. 29048832 7 34 theme @ 1523:1523 arg1 SiO2 1524:1527 Mal@SiO2 1520:1527 Mal@SiO2 1520:1527 In contrast, the numbers of identified glycopeptides, glycoproteins and N-glycosylation sites identified by Cys@SiO2 were 211, 67, 127 respectively less than by Cys-Mal@SiO2, and the corresponding numbers were 289, 76, 193 by Mal@SiO2. 29048832 4 35 theme hydrophilic 778:788 arg1 chromatography 809:822 commercial hydrophilic interaction liquid chromatography 767:822 commercial hydrophilic interaction liquid chromatography (HILIC) 767:830 The Cys-Mal@SiO2 demonstrated better identification capability over Cys@SiO2, Mal@SiO2 and commercial hydrophilic interaction liquid chromatography (HILIC) in glycopeptide enrichment due to the synergistic effect of the two kinds of hydrophilic molecules. 29048832 4 35 theme hydrophilic 778:788 arg1 HILIC 825:829 HILIC 825:829 HILIC 825:829 The Cys-Mal@SiO2 demonstrated better identification capability over Cys@SiO2, Mal@SiO2 and commercial hydrophilic interaction liquid chromatography (HILIC) in glycopeptide enrichment due to the synergistic effect of the two kinds of hydrophilic molecules. 29048832 7 36 gly glycoproteins 1348:1360 arg1 glycoproteins 1348:1360 glycoproteins 1348:1360 glycoproteins 1348:1360 In contrast, the numbers of identified glycopeptides, glycoproteins and N-glycosylation sites identified by Cys@SiO2 were 211, 67, 127 respectively less than by Cys-Mal@SiO2, and the corresponding numbers were 289, 76, 193 by Mal@SiO2. 29048832 5 37 theme immunoglobulin 989:1002 arg1 G 1004:1004 human immunoglobulin G 983:1004 human immunoglobulin G 983:1004 In the selective enrichment of tryptic digest from human immunoglobulin G, glycopeptides with higher signal-to-noises were detected by Cys-Mal@SiO2. 29048832 2 38 theme Cys-Mal 480:486 arg1 SiO2 488:491 Cys-Mal@SiO2 480:491 Cys-Mal@SiO2 480:491 Herein, a novel hydrophilic silica was developed through surface modification with cysteine-click maltose (Cys-Mal@SiO2). 29048832 2 38 theme Cys-Mal 480:486 arg1 maltose 471:477 cysteine-click maltose 456:477 cysteine-click maltose (Cys-Mal@SiO2) 456:492 Herein, a novel hydrophilic silica was developed through surface modification with cysteine-click maltose (Cys-Mal@SiO2). 29048832 1 39 theme efficient 273:281 arg1 method 283:288 an efficient method 270:288 an efficient method for glycopeptide enrichment in comprehensive and in-depth glycoproteomes research 270:370 Because of the low abundance of glycoprotein and glycopeptide in complex biological samples, it is urgent to develop an efficient method for glycopeptide enrichment in comprehensive and in-depth glycoproteomes research. 29048832 7 40 gly glycopeptides 1333:1345 arg2 glycopeptides 1333:1345 identified glycopeptides 1322:1345 identified glycopeptides 1322:1345 In contrast, the numbers of identified glycopeptides, glycoproteins and N-glycosylation sites identified by Cys@SiO2 were 211, 67, 127 respectively less than by Cys-Mal@SiO2, and the corresponding numbers were 289, 76, 193 by Mal@SiO2. 29048832 4 41 theme @ 757:757 arg1 SiO2 758:761 Mal@SiO2 754:761 Mal@SiO2 754:761 The Cys-Mal@SiO2 demonstrated better identification capability over Cys@SiO2, Mal@SiO2 and commercial hydrophilic interaction liquid chromatography (HILIC) in glycopeptide enrichment due to the synergistic effect of the two kinds of hydrophilic molecules. 29048832 0 42 theme cysteine-click 16:29 arg1 maltose 31:37 cysteine-click maltose 16:37 cysteine-click maltose 16:37 [Preparation of cysteine-click maltose modified silica as a hydrophilic interaction liquid chromatography material for the enrichment of glycopeptides]. 29048832 5 43 theme tryptic 963:969 arg1 digest 971:976 tryptic digest 963:976 tryptic digest 963:976 In the selective enrichment of tryptic digest from human immunoglobulin G, glycopeptides with higher signal-to-noises were detected by Cys-Mal@SiO2. 29048832 7 44 theme identified 1322:1331 arg1 glycopeptides 1333:1345 identified glycopeptides 1322:1345 identified glycopeptides 1322:1345 In contrast, the numbers of identified glycopeptides, glycoproteins and N-glycosylation sites identified by Cys@SiO2 were 211, 67, 127 respectively less than by Cys-Mal@SiO2, and the corresponding numbers were 289, 76, 193 by Mal@SiO2. 29048832 3 45 theme glycopeptides 661:673 arg1 identification 634:647 identification 634:647 identification 634:647 The developed hydrophilic silica was packed into a solid phase extraction (SPE) column, and applied to the highly selective enrichment and identification of N-linked glycopeptides. 29048832 3 45 theme glycopeptides 661:673 arg1 enrichment 619:628 enrichment 619:628 enrichment 619:628 The developed hydrophilic silica was packed into a solid phase extraction (SPE) column, and applied to the highly selective enrichment and identification of N-linked glycopeptides. 29048832 2 46 theme surface 430:436 arg1 modification 438:449 surface modification 430:449 surface modification with cysteine-click maltose (Cys-Mal@SiO2) 430:492 Herein, a novel hydrophilic silica was developed through surface modification with cysteine-click maltose (Cys-Mal@SiO2). 29048832 4 47 theme glycopeptide 835:846 arg1 enrichment 848:857 glycopeptide enrichment 835:857 glycopeptide enrichment due to the synergistic effect of the two kinds of hydrophilic molecules 835:929 The Cys-Mal@SiO2 demonstrated better identification capability over Cys@SiO2, Mal@SiO2 and commercial hydrophilic interaction liquid chromatography (HILIC) in glycopeptide enrichment due to the synergistic effect of the two kinds of hydrophilic molecules. 29048832 3 48 theme hydrophilic 509:519 arg1 silica 521:526 The developed hydrophilic silica 495:526 The developed hydrophilic silica 495:526 The developed hydrophilic silica was packed into a solid phase extraction (SPE) column, and applied to the highly selective enrichment and identification of N-linked glycopeptides. 29048832 1 49 theme comprehensive 321:333 arg1 research 363:370 comprehensive and in-depth glycoproteomes research 321:370 comprehensive and in-depth glycoproteomes research 321:370 Because of the low abundance of glycoprotein and glycopeptide in complex biological samples, it is urgent to develop an efficient method for glycopeptide enrichment in comprehensive and in-depth glycoproteomes research. 29048832 6 50 theme @ 1287:1287 arg1 SiO2 1288:1291 Cys-Mal@SiO2 1280:1291 Cys-Mal@SiO2 1280:1291 In addition, 1551 unique glycopeptides with 906 N-glycosylation sites from 466 different N-linked glycoproteins were identified from the proteins extracted from mouse liver after the enrichment with Cys-Mal@SiO2. 29048832 3 51 theme selective 609:617 arg1 enrichment 619:628 enrichment 619:628 enrichment 619:628 The developed hydrophilic silica was packed into a solid phase extraction (SPE) column, and applied to the highly selective enrichment and identification of N-linked glycopeptides. 29048832 4 52 theme liquid 802:807 arg1 chromatography 809:822 commercial hydrophilic interaction liquid chromatography 767:822 commercial hydrophilic interaction liquid chromatography (HILIC) 767:830 The Cys-Mal@SiO2 demonstrated better identification capability over Cys@SiO2, Mal@SiO2 and commercial hydrophilic interaction liquid chromatography (HILIC) in glycopeptide enrichment due to the synergistic effect of the two kinds of hydrophilic molecules. 29048832 4 52 theme liquid 802:807 arg1 HILIC 825:829 HILIC 825:829 HILIC 825:829 The Cys-Mal@SiO2 demonstrated better identification capability over Cys@SiO2, Mal@SiO2 and commercial hydrophilic interaction liquid chromatography (HILIC) in glycopeptide enrichment due to the synergistic effect of the two kinds of hydrophilic molecules. 29048832 8 53 theme affinity 1598:1605 arg1 material 1607:1614 a promising affinity material 1586:1614 a promising affinity material for N-glycoproteomics research of real complex biological samples 1586:1680 These results showed that the developed Cys-Mal@SiO2 is a promising affinity material for N-glycoproteomics research of real complex biological samples. 29048832 8 53 theme affinity 1598:1605 arg1 SiO2 1578:1581 the developed Cys-Mal@SiO2 1556:1581 the developed Cys-Mal@SiO2 1556:1581 These results showed that the developed Cys-Mal@SiO2 is a promising affinity material for N-glycoproteomics research of real complex biological samples. 29048832 5 54 with glycopeptides 1007:1019 arg1 signal-to-noises 1033:1048 higher signal-to-noises 1026:1048 higher signal-to-noises 1026:1048 In the selective enrichment of tryptic digest from human immunoglobulin G, glycopeptides with higher signal-to-noises were detected by Cys-Mal@SiO2. 29048832 2 55 theme novel 383:387 arg1 silica 401:406 a novel hydrophilic silica 381:406 a novel hydrophilic silica 381:406 Herein, a novel hydrophilic silica was developed through surface modification with cysteine-click maltose (Cys-Mal@SiO2). 29048832 5 56 located detected 1055:1062 arg1 enrichment 949:958 the selective enrichment 935:958 the selective enrichment of tryptic digest from human immunoglobulin G 935:1004 In the selective enrichment of tryptic digest from human immunoglobulin G, glycopeptides with higher signal-to-noises were detected by Cys-Mal@SiO2. 29048832 5 56 located detected 1055:1062 arg2 glycopeptides 1007:1019 glycopeptides 1007:1019 glycopeptides with higher signal-to-noises 1007:1048 In the selective enrichment of tryptic digest from human immunoglobulin G, glycopeptides with higher signal-to-noises were detected by Cys-Mal@SiO2. 29048832 8 57 theme Cys-Mal 1570:1576 arg1 material 1607:1614 a promising affinity material 1586:1614 a promising affinity material for N-glycoproteomics research of real complex biological samples 1586:1680 These results showed that the developed Cys-Mal@SiO2 is a promising affinity material for N-glycoproteomics research of real complex biological samples. 29048832 8 57 theme Cys-Mal 1570:1576 arg1 SiO2 1578:1581 the developed Cys-Mal@SiO2 1556:1581 the developed Cys-Mal@SiO2 1556:1581 These results showed that the developed Cys-Mal@SiO2 is a promising affinity material for N-glycoproteomics research of real complex biological samples. 29048832 6 58 with glycopeptides 1106:1118 arg1 sites 1145:1149 906 N-glycosylation sites 1125:1149 906 N-glycosylation sites 1125:1149 In addition, 1551 unique glycopeptides with 906 N-glycosylation sites from 466 different N-linked glycoproteins were identified from the proteins extracted from mouse liver after the enrichment with Cys-Mal@SiO2. 29048832 4 59 theme synergistic 870:880 arg1 effect 882:887 the synergistic effect 866:887 the synergistic effect of the two kinds of hydrophilic molecules 866:929 The Cys-Mal@SiO2 demonstrated better identification capability over Cys@SiO2, Mal@SiO2 and commercial hydrophilic interaction liquid chromatography (HILIC) in glycopeptide enrichment due to the synergistic effect of the two kinds of hydrophilic molecules. 29048832 3 60 link N-linked 652:659 arg1 glycopeptides 661:673 N-linked glycopeptides 652:673 N-linked glycopeptides 652:673 The developed hydrophilic silica was packed into a solid phase extraction (SPE) column, and applied to the highly selective enrichment and identification of N-linked glycopeptides. 29048832 1 61 from enrichment 307:316 arg1 research 363:370 comprehensive and in-depth glycoproteomes research 321:370 comprehensive and in-depth glycoproteomes research 321:370 Because of the low abundance of glycoprotein and glycopeptide in complex biological samples, it is urgent to develop an efficient method for glycopeptide enrichment in comprehensive and in-depth glycoproteomes research. 29048832 3 62 theme extraction 558:567 arg1 column 575:580 a solid phase extraction (SPE) column 544:580 a solid phase extraction (SPE) column 544:580 The developed hydrophilic silica was packed into a solid phase extraction (SPE) column, and applied to the highly selective enrichment and identification of N-linked glycopeptides. 29048832 8 63 theme real 1650:1653 arg1 samples 1674:1680 real complex biological samples 1650:1680 real complex biological samples 1650:1680 These results showed that the developed Cys-Mal@SiO2 is a promising affinity material for N-glycoproteomics research of real complex biological samples. 29048832 7 64 theme @ 1462:1462 arg1 SiO2 1463:1466 Cys-Mal@SiO2 1455:1466 Cys-Mal@SiO2 1455:1466 In contrast, the numbers of identified glycopeptides, glycoproteins and N-glycosylation sites identified by Cys@SiO2 were 211, 67, 127 respectively less than by Cys-Mal@SiO2, and the corresponding numbers were 289, 76, 193 by Mal@SiO2. 29048832 3 65 theme solid 546:550 arg1 column 575:580 a solid phase extraction (SPE) column 544:580 a solid phase extraction (SPE) column 544:580 The developed hydrophilic silica was packed into a solid phase extraction (SPE) column, and applied to the highly selective enrichment and identification of N-linked glycopeptides. 29048832 8 66 theme biological 1663:1672 arg1 samples 1674:1680 real complex biological samples 1650:1680 real complex biological samples 1650:1680 These results showed that the developed Cys-Mal@SiO2 is a promising affinity material for N-glycoproteomics research of real complex biological samples. 29048832 1 67 theme abundance 172:180 arg1 urgent 252:257 urgent 252:257 urgent 252:257 Because of the low abundance of glycoprotein and glycopeptide in complex biological samples, it is urgent to develop an efficient method for glycopeptide enrichment in comprehensive and in-depth glycoproteomes research. 29048832 2 68 theme @ 487:487 arg1 SiO2 488:491 Cys-Mal@SiO2 480:491 Cys-Mal@SiO2 480:491 Herein, a novel hydrophilic silica was developed through surface modification with cysteine-click maltose (Cys-Mal@SiO2). 29048832 2 68 theme @ 487:487 arg1 maltose 471:477 cysteine-click maltose 456:477 cysteine-click maltose (Cys-Mal@SiO2) 456:492 Herein, a novel hydrophilic silica was developed through surface modification with cysteine-click maltose (Cys-Mal@SiO2). 29048832 6 69 theme Cys-Mal 1280:1286 arg1 SiO2 1288:1291 Cys-Mal@SiO2 1280:1291 Cys-Mal@SiO2 1280:1291 In addition, 1551 unique glycopeptides with 906 N-glycosylation sites from 466 different N-linked glycoproteins were identified from the proteins extracted from mouse liver after the enrichment with Cys-Mal@SiO2. 29048832 1 70 theme glycoprotein 185:196 arg1 abundance 172:180 the low abundance 164:180 the low abundance of glycoprotein and glycopeptide in complex biological samples 164:243 Because of the low abundance of glycoprotein and glycopeptide in complex biological samples, it is urgent to develop an efficient method for glycopeptide enrichment in comprehensive and in-depth glycoproteomes research. 29048832 6 71 theme N-linked 1170:1177 arg1 glycoproteins 1179:1191 466 different N-linked glycoproteins 1156:1191 466 different N-linked glycoproteins 1156:1191 In addition, 1551 unique glycopeptides with 906 N-glycosylation sites from 466 different N-linked glycoproteins were identified from the proteins extracted from mouse liver after the enrichment with Cys-Mal@SiO2. 29048832 4 72 theme Cys-Mal 680:686 arg1 SiO2 688:691 The Cys-Mal@SiO2 676:691 The Cys-Mal@SiO2 676:691 The Cys-Mal@SiO2 demonstrated better identification capability over Cys@SiO2, Mal@SiO2 and commercial hydrophilic interaction liquid chromatography (HILIC) in glycopeptide enrichment due to the synergistic effect of the two kinds of hydrophilic molecules. 29048832 0 73 theme glycopeptides 137:149 arg1 enrichment 123:132 the enrichment 119:132 the enrichment of glycopeptides 119:149 [Preparation of cysteine-click maltose modified silica as a hydrophilic interaction liquid chromatography material for the enrichment of glycopeptides]. 29048832 3 74 theme SPE 570:572 arg1 column 575:580 a solid phase extraction (SPE) column 544:580 a solid phase extraction (SPE) column 544:580 The developed hydrophilic silica was packed into a solid phase extraction (SPE) column, and applied to the highly selective enrichment and identification of N-linked glycopeptides. 29048832 1 75 theme glycopeptide 202:213 arg1 abundance 172:180 the low abundance 164:180 the low abundance of glycoprotein and glycopeptide in complex biological samples 164:243 Because of the low abundance of glycoprotein and glycopeptide in complex biological samples, it is urgent to develop an efficient method for glycopeptide enrichment in comprehensive and in-depth glycoproteomes research. 29048832 7 76 gly N-glycosylation 1366:1380 arg2 sites 1382:1386 N-glycosylation sites 1366:1386 N-glycosylation sites 1366:1386 In contrast, the numbers of identified glycopeptides, glycoproteins and N-glycosylation sites identified by Cys@SiO2 were 211, 67, 127 respectively less than by Cys-Mal@SiO2, and the corresponding numbers were 289, 76, 193 by Mal@SiO2. 29048832 4 77 theme molecules 921:929 arg1 kinds 900:904 the two kinds 892:904 the two kinds of hydrophilic molecules 892:929 The Cys-Mal@SiO2 demonstrated better identification capability over Cys@SiO2, Mal@SiO2 and commercial hydrophilic interaction liquid chromatography (HILIC) in glycopeptide enrichment due to the synergistic effect of the two kinds of hydrophilic molecules. 29048832 1 78 theme complex 218:224 arg1 samples 237:243 complex biological samples 218:243 complex biological samples 218:243 Because of the low abundance of glycoprotein and glycopeptide in complex biological samples, it is urgent to develop an efficient method for glycopeptide enrichment in comprehensive and in-depth glycoproteomes research. 29048832 7 79 theme Cys-Mal 1455:1461 arg1 SiO2 1463:1466 Cys-Mal@SiO2 1455:1466 Cys-Mal@SiO2 1455:1466 In contrast, the numbers of identified glycopeptides, glycoproteins and N-glycosylation sites identified by Cys@SiO2 were 211, 67, 127 respectively less than by Cys-Mal@SiO2, and the corresponding numbers were 289, 76, 193 by Mal@SiO2. 29048832 7 80 dep 127 1425:1427 arg1 less 1442:1445 less 1442:1445 less 1442:1445 In contrast, the numbers of identified glycopeptides, glycoproteins and N-glycosylation sites identified by Cys@SiO2 were 211, 67, 127 respectively less than by Cys-Mal@SiO2, and the corresponding numbers were 289, 76, 193 by Mal@SiO2. 29048832 7 81 theme @ 1405:1405 arg1 SiO2 1406:1409 Cys@SiO2 1402:1409 Cys@SiO2 1402:1409 In contrast, the numbers of identified glycopeptides, glycoproteins and N-glycosylation sites identified by Cys@SiO2 were 211, 67, 127 respectively less than by Cys-Mal@SiO2, and the corresponding numbers were 289, 76, 193 by Mal@SiO2. 29048832 5 82 theme Cys-Mal 1067:1073 arg1 SiO2 1075:1078 Cys-Mal@SiO2 1067:1078 Cys-Mal@SiO2 1067:1078 In the selective enrichment of tryptic digest from human immunoglobulin G, glycopeptides with higher signal-to-noises were detected by Cys-Mal@SiO2. 29048832 4 83 theme Cys 744:746 arg1 SiO2 748:751 Cys@SiO2 744:751 Cys@SiO2 744:751 The Cys-Mal@SiO2 demonstrated better identification capability over Cys@SiO2, Mal@SiO2 and commercial hydrophilic interaction liquid chromatography (HILIC) in glycopeptide enrichment due to the synergistic effect of the two kinds of hydrophilic molecules. 29048832 0 84 theme interaction 72:82 arg1 chromatography 91:104 a hydrophilic interaction liquid chromatography 58:104 a hydrophilic interaction liquid chromatography material 58:113 [Preparation of cysteine-click maltose modified silica as a hydrophilic interaction liquid chromatography material for the enrichment of glycopeptides]. 29048832 6 85 with enrichment 1264:1273 arg1 SiO2 1288:1291 Cys-Mal@SiO2 1280:1291 Cys-Mal@SiO2 1280:1291 In addition, 1551 unique glycopeptides with 906 N-glycosylation sites from 466 different N-linked glycoproteins were identified from the proteins extracted from mouse liver after the enrichment with Cys-Mal@SiO2. 29048832 7 86 theme sites 1382:1386 arg1 numbers 1311:1317 the numbers 1307:1317 the numbers of identified glycopeptides, glycoproteins and N-glycosylation sites identified by Cys@SiO2 1307:1409 In contrast, the numbers of identified glycopeptides, glycoproteins and N-glycosylation sites identified by Cys@SiO2 were 211, 67, 127 respectively less than by Cys-Mal@SiO2, and the corresponding numbers were 289, 76, 193 by Mal@SiO2. 29048832 7 86 theme sites 1382:1386 arg1 127 1425:1427 127 1425:1427 127 1425:1427 In contrast, the numbers of identified glycopeptides, glycoproteins and N-glycosylation sites identified by Cys@SiO2 were 211, 67, 127 respectively less than by Cys-Mal@SiO2, and the corresponding numbers were 289, 76, 193 by Mal@SiO2. 29048832 0 87 theme chromatography 91:104 arg1 material 106:113 a hydrophilic interaction liquid chromatography material 58:113 a hydrophilic interaction liquid chromatography material 58:113 [Preparation of cysteine-click maltose modified silica as a hydrophilic interaction liquid chromatography material for the enrichment of glycopeptides]. 29048832 1 88 theme glycoproteomes 348:361 arg1 research 363:370 comprehensive and in-depth glycoproteomes research 321:370 comprehensive and in-depth glycoproteomes research 321:370 Because of the low abundance of glycoprotein and glycopeptide in complex biological samples, it is urgent to develop an efficient method for glycopeptide enrichment in comprehensive and in-depth glycoproteomes research. 29048832 4 89 theme better 706:711 arg1 capability 728:737 better identification capability 706:737 better identification capability 706:737 The Cys-Mal@SiO2 demonstrated better identification capability over Cys@SiO2, Mal@SiO2 and commercial hydrophilic interaction liquid chromatography (HILIC) in glycopeptide enrichment due to the synergistic effect of the two kinds of hydrophilic molecules. 29048832 5 90 theme digest 971:976 arg1 enrichment 949:958 the selective enrichment 935:958 the selective enrichment of tryptic digest from human immunoglobulin G 935:1004 In the selective enrichment of tryptic digest from human immunoglobulin G, glycopeptides with higher signal-to-noises were detected by Cys-Mal@SiO2. 29048832 7 91 theme Mal 1520:1522 arg1 SiO2 1524:1527 Mal@SiO2 1520:1527 Mal@SiO2 1520:1527 In contrast, the numbers of identified glycopeptides, glycoproteins and N-glycosylation sites identified by Cys@SiO2 were 211, 67, 127 respectively less than by Cys-Mal@SiO2, and the corresponding numbers were 289, 76, 193 by Mal@SiO2. 29048832 6 92 link N-linked 1170:1177 arg1 glycoproteins 1179:1191 466 different N-linked glycoproteins 1156:1191 466 different N-linked glycoproteins 1156:1191 In addition, 1551 unique glycopeptides with 906 N-glycosylation sites from 466 different N-linked glycoproteins were identified from the proteins extracted from mouse liver after the enrichment with Cys-Mal@SiO2. 29048832 5 93 theme human 983:987 arg1 G 1004:1004 human immunoglobulin G 983:1004 human immunoglobulin G 983:1004 In the selective enrichment of tryptic digest from human immunoglobulin G, glycopeptides with higher signal-to-noises were detected by Cys-Mal@SiO2. 29048832 7 94 theme glycoproteins 1348:1360 arg1 numbers 1311:1317 the numbers 1307:1317 the numbers of identified glycopeptides, glycoproteins and N-glycosylation sites identified by Cys@SiO2 1307:1409 In contrast, the numbers of identified glycopeptides, glycoproteins and N-glycosylation sites identified by Cys@SiO2 were 211, 67, 127 respectively less than by Cys-Mal@SiO2, and the corresponding numbers were 289, 76, 193 by Mal@SiO2. 29048832 7 94 theme glycoproteins 1348:1360 arg1 127 1425:1427 127 1425:1427 127 1425:1427 In contrast, the numbers of identified glycopeptides, glycoproteins and N-glycosylation sites identified by Cys@SiO2 were 211, 67, 127 respectively less than by Cys-Mal@SiO2, and the corresponding numbers were 289, 76, 193 by Mal@SiO2. 29048832 4 95 theme commercial 767:776 arg1 chromatography 809:822 commercial hydrophilic interaction liquid chromatography 767:822 commercial hydrophilic interaction liquid chromatography (HILIC) 767:830 The Cys-Mal@SiO2 demonstrated better identification capability over Cys@SiO2, Mal@SiO2 and commercial hydrophilic interaction liquid chromatography (HILIC) in glycopeptide enrichment due to the synergistic effect of the two kinds of hydrophilic molecules. 29048832 4 95 theme commercial 767:776 arg1 HILIC 825:829 HILIC 825:829 HILIC 825:829 The Cys-Mal@SiO2 demonstrated better identification capability over Cys@SiO2, Mal@SiO2 and commercial hydrophilic interaction liquid chromatography (HILIC) in glycopeptide enrichment due to the synergistic effect of the two kinds of hydrophilic molecules. 29048832 5 96 theme selective 939:947 arg1 enrichment 949:958 the selective enrichment 935:958 the selective enrichment of tryptic digest from human immunoglobulin G 935:1004 In the selective enrichment of tryptic digest from human immunoglobulin G, glycopeptides with higher signal-to-noises were detected by Cys-Mal@SiO2. 29048832 7 97 theme glycopeptides 1333:1345 arg1 numbers 1311:1317 the numbers 1307:1317 the numbers of identified glycopeptides, glycoproteins and N-glycosylation sites identified by Cys@SiO2 1307:1409 In contrast, the numbers of identified glycopeptides, glycoproteins and N-glycosylation sites identified by Cys@SiO2 were 211, 67, 127 respectively less than by Cys-Mal@SiO2, and the corresponding numbers were 289, 76, 193 by Mal@SiO2. 29048832 7 97 theme glycopeptides 1333:1345 arg1 127 1425:1427 127 1425:1427 127 1425:1427 In contrast, the numbers of identified glycopeptides, glycoproteins and N-glycosylation sites identified by Cys@SiO2 were 211, 67, 127 respectively less than by Cys-Mal@SiO2, and the corresponding numbers were 289, 76, 193 by Mal@SiO2. 29048832 6 98 gly N-glycosylation 1129:1143 arg2 sites 1145:1149 906 N-glycosylation sites 1125:1149 906 N-glycosylation sites 1125:1149 In addition, 1551 unique glycopeptides with 906 N-glycosylation sites from 466 different N-linked glycoproteins were identified from the proteins extracted from mouse liver after the enrichment with Cys-Mal@SiO2. 29048832 6 98 gly N-glycosylation 1129:1143 arg2 906 1125:1127 906 1125:1127 906 1125:1127 In addition, 1551 unique glycopeptides with 906 N-glycosylation sites from 466 different N-linked glycoproteins were identified from the proteins extracted from mouse liver after the enrichment with Cys-Mal@SiO2. 29048832 2 99 theme hydrophilic 389:399 arg1 silica 401:406 a novel hydrophilic silica 381:406 a novel hydrophilic silica 381:406 Herein, a novel hydrophilic silica was developed through surface modification with cysteine-click maltose (Cys-Mal@SiO2). 29048832 0 100 theme maltose 31:37 arg1 [Preparation 0:11 [Preparation 0:11 [Preparation of cysteine-click maltose 0:37 [Preparation of cysteine-click maltose modified silica as a hydrophilic interaction liquid chromatography material for the enrichment of glycopeptides]. 29048832 2 101 theme cysteine-click 456:469 arg1 SiO2 488:491 Cys-Mal@SiO2 480:491 Cys-Mal@SiO2 480:491 Herein, a novel hydrophilic silica was developed through surface modification with cysteine-click maltose (Cys-Mal@SiO2). 29048832 2 101 theme cysteine-click 456:469 arg1 maltose 471:477 cysteine-click maltose 456:477 cysteine-click maltose (Cys-Mal@SiO2) 456:492 Herein, a novel hydrophilic silica was developed through surface modification with cysteine-click maltose (Cys-Mal@SiO2). 29048832 3 102 theme N-linked 652:659 arg1 glycopeptides 661:673 N-linked glycopeptides 652:673 N-linked glycopeptides 652:673 The developed hydrophilic silica was packed into a solid phase extraction (SPE) column, and applied to the highly selective enrichment and identification of N-linked glycopeptides. 29048832 4 103 theme Mal 754:756 arg1 SiO2 758:761 Mal@SiO2 754:761 Mal@SiO2 754:761 The Cys-Mal@SiO2 demonstrated better identification capability over Cys@SiO2, Mal@SiO2 and commercial hydrophilic interaction liquid chromatography (HILIC) in glycopeptide enrichment due to the synergistic effect of the two kinds of hydrophilic molecules. 29048832 6 104 from glycoproteins 1179:1191 arg1 glycopeptides 1106:1118 1551 unique glycopeptides 1094:1118 1551 unique glycopeptides with 906 N-glycosylation sites from 466 different N-linked glycoproteins 1094:1191 In addition, 1551 unique glycopeptides with 906 N-glycosylation sites from 466 different N-linked glycoproteins were identified from the proteins extracted from mouse liver after the enrichment with Cys-Mal@SiO2. 29048832 1 105 theme glycopeptide 294:305 arg1 enrichment 307:316 glycopeptide enrichment 294:316 glycopeptide enrichment in comprehensive and in-depth glycoproteomes research 294:370 Because of the low abundance of glycoprotein and glycopeptide in complex biological samples, it is urgent to develop an efficient method for glycopeptide enrichment in comprehensive and in-depth glycoproteomes research. 29048832 3 106 dep enrichment 619:628 arg1 the 598:600 the 598:600 the 598:600 The developed hydrophilic silica was packed into a solid phase extraction (SPE) column, and applied to the highly selective enrichment and identification of N-linked glycopeptides. 29048832 5 107 theme higher 1026:1031 arg1 signal-to-noises 1033:1048 higher signal-to-noises 1026:1048 higher signal-to-noises 1026:1048 In the selective enrichment of tryptic digest from human immunoglobulin G, glycopeptides with higher signal-to-noises were detected by Cys-Mal@SiO2. 29048832 5 108 gly glycopeptides 1007:1019 arg2 glycopeptides 1007:1019 glycopeptides 1007:1019 glycopeptides with higher signal-to-noises 1007:1048 In the selective enrichment of tryptic digest from human immunoglobulin G, glycopeptides with higher signal-to-noises were detected by Cys-Mal@SiO2. 29048832 6 109 theme N-glycosylation 1129:1143 arg1 sites 1145:1149 906 N-glycosylation sites 1125:1149 906 N-glycosylation sites 1125:1149 In addition, 1551 unique glycopeptides with 906 N-glycosylation sites from 466 different N-linked glycoproteins were identified from the proteins extracted from mouse liver after the enrichment with Cys-Mal@SiO2. 29048832 8 110 theme developed 1560:1568 arg1 material 1607:1614 a promising affinity material 1586:1614 a promising affinity material for N-glycoproteomics research of real complex biological samples 1586:1680 These results showed that the developed Cys-Mal@SiO2 is a promising affinity material for N-glycoproteomics research of real complex biological samples. 29048832 8 110 theme developed 1560:1568 arg1 SiO2 1578:1581 the developed Cys-Mal@SiO2 1556:1581 the developed Cys-Mal@SiO2 1556:1581 These results showed that the developed Cys-Mal@SiO2 is a promising affinity material for N-glycoproteomics research of real complex biological samples. 29048832 4 111 theme interaction 790:800 arg1 chromatography 809:822 commercial hydrophilic interaction liquid chromatography 767:822 commercial hydrophilic interaction liquid chromatography (HILIC) 767:830 The Cys-Mal@SiO2 demonstrated better identification capability over Cys@SiO2, Mal@SiO2 and commercial hydrophilic interaction liquid chromatography (HILIC) in glycopeptide enrichment due to the synergistic effect of the two kinds of hydrophilic molecules. 29048832 4 111 theme interaction 790:800 arg1 HILIC 825:829 HILIC 825:829 HILIC 825:829 The Cys-Mal@SiO2 demonstrated better identification capability over Cys@SiO2, Mal@SiO2 and commercial hydrophilic interaction liquid chromatography (HILIC) in glycopeptide enrichment due to the synergistic effect of the two kinds of hydrophilic molecules. 29048832 3 112 theme developed 499:507 arg1 silica 521:526 The developed hydrophilic silica 495:526 The developed hydrophilic silica 495:526 The developed hydrophilic silica was packed into a solid phase extraction (SPE) column, and applied to the highly selective enrichment and identification of N-linked glycopeptides. 29048832 8 113 theme N-glycoproteomics 1620:1636 arg1 research 1638:1645 N-glycoproteomics research 1620:1645 N-glycoproteomics research of real complex biological samples 1620:1680 These results showed that the developed Cys-Mal@SiO2 is a promising affinity material for N-glycoproteomics research of real complex biological samples. 29048832 8 114 theme @ 1577:1577 arg1 material 1607:1614 a promising affinity material 1586:1614 a promising affinity material for N-glycoproteomics research of real complex biological samples 1586:1680 These results showed that the developed Cys-Mal@SiO2 is a promising affinity material for N-glycoproteomics research of real complex biological samples. 29048832 8 114 theme @ 1577:1577 arg1 SiO2 1578:1581 the developed Cys-Mal@SiO2 1556:1581 the developed Cys-Mal@SiO2 1556:1581 These results showed that the developed Cys-Mal@SiO2 is a promising affinity material for N-glycoproteomics research of real complex biological samples. 27026706 8 0 theme acids 1201:1205 arg1 Substitutions 1178:1190 Substitutions 1178:1190 Substitutions of amino acids within zebra finch CBG that are conserved only in birds 1178:1261 Substitutions of amino acids within zebra finch CBG that are conserved only in birds reveal how they contribute to their distinct steroid-binding properties, including their high (nanomolar) affinities for glucocorticoids, progesterone, and androgens. 27026706 6 1 theme unexpected 953:962 arg1 property 964:971 this unexpected property 948:971 this unexpected property 948:971 Phylogenetic comparisons show that reptilian CBG orthologs share this unexpected property. 27026706 2 2 theme avian 367:371 arg1 genes 396:400 avian and mammalian SerpinA6 genes 367:400 avian and mammalian SerpinA6 genes 367:400 This revealed that the organization and synteny of avian and mammalian SerpinA6 genes are conserved. 27026706 8 3 theme zebra 1214:1218 arg1 finch 1220:1224 zebra finch 1214:1224 zebra finch CBG 1214:1228 Substitutions of amino acids within zebra finch CBG that are conserved only in birds reveal how they contribute to their distinct steroid-binding properties, including their high (nanomolar) affinities for glucocorticoids, progesterone, and androgens. 27026706 7 4 theme site 1162:1165 arg1 formation 1167:1175 steroid-binding site formation 1146:1175 steroid-binding site formation 1146:1175 Glycosylation of this asparagine in zebra finch CBG does not influence its steroid-binding affinity, but we present evidence that it may participate in protein folding and steroid-binding site formation. 27026706 6 5 theme CBG 928:930 arg1 orthologs 932:940 reptilian CBG orthologs 918:940 reptilian CBG orthologs 918:940 Phylogenetic comparisons show that reptilian CBG orthologs share this unexpected property. 27026706 10 6 theme CBG 1776:1778 arg1 antibodies 1780:1789 anti-zebra finch CBG antibodies 1759:1789 anti-zebra finch CBG antibodies 1759:1789 Measurements of CBG mRNA in zebra finch tissues indicate that liver is the main site of plasma CBG production, and anti-zebra finch CBG antibodies cross-react with CBGs in other birds, extending opportunities to study how CBG regulates the actions of glucocorticoids and sex steroids in these species. 27026706 1 7 theme Corticosteroid-binding 188:209 arg1 globulin 211:218 Corticosteroid-binding globulin 188:218 Corticosteroid-binding globulin (CBG) 188:224 Corticosteroid-binding globulin (CBG) was isolated from chicken serum and identified by mass spectrometry and genomic analysis. 27026706 1 7 theme Corticosteroid-binding 188:209 arg1 CBG 221:223 CBG 221:223 CBG 221:223 Corticosteroid-binding globulin (CBG) was isolated from chicken serum and identified by mass spectrometry and genomic analysis. 27026706 7 8 theme protein 1126:1132 arg1 folding 1134:1140 protein folding 1126:1140 protein folding 1126:1140 Glycosylation of this asparagine in zebra finch CBG does not influence its steroid-binding affinity, but we present evidence that it may participate in protein folding and steroid-binding site formation. 27026706 10 9 theme other 1816:1820 arg1 birds 1822:1826 other birds 1816:1826 other birds 1816:1826 Measurements of CBG mRNA in zebra finch tissues indicate that liver is the main site of plasma CBG production, and anti-zebra finch CBG antibodies cross-react with CBGs in other birds, extending opportunities to study how CBG regulates the actions of glucocorticoids and sex steroids in these species. 27026706 8 10 theme steroid-binding 1308:1322 arg1 affinities 1369:1378 their high (nanomolar) affinities 1346:1378 their high (nanomolar) affinities for glucocorticoids, progesterone, and androgens 1346:1427 Substitutions of amino acids within zebra finch CBG that are conserved only in birds reveal how they contribute to their distinct steroid-binding properties, including their high (nanomolar) affinities for glucocorticoids, progesterone, and androgens. 27026706 8 10 theme steroid-binding 1308:1322 arg1 properties 1324:1333 their distinct steroid-binding properties 1293:1333 their distinct steroid-binding properties 1293:1333 Substitutions of amino acids within zebra finch CBG that are conserved only in birds reveal how they contribute to their distinct steroid-binding properties, including their high (nanomolar) affinities for glucocorticoids, progesterone, and androgens. 27026706 2 11 dep organization 339:350 arg1 the 335:337 the 335:337 the 335:337 This revealed that the organization and synteny of avian and mammalian SerpinA6 genes are conserved. 27026706 0 12 theme SerpinA6 126:133 arg1 Structure 135:143 SerpinA6 Structure 126:143 SerpinA6 Structure 126:143 Identification of Avian Corticosteroid-binding Globulin (SerpinA6) Reveals the Molecular Basis of Evolutionary Adaptations in SerpinA6 Structure and Function as a Steroid-binding Protein. 27026706 9 13 theme finch 1512:1516 arg1 plasma 1518:1523 zebra finch plasma 1506:1523 zebra finch plasma 1506:1523 As in mammals, a protease secreted by Pseudomonas aeruginosa cleaves CBG in zebra finch plasma within its reactive center loop and disrupts steroid binding, suggesting an evolutionarily conserved property of CBGs. 27026706 10 14 theme zebra 1672:1676 arg1 finch 1678:1682 zebra finch 1672:1682 zebra finch tissues 1672:1690 Measurements of CBG mRNA in zebra finch tissues indicate that liver is the main site of plasma CBG production, and anti-zebra finch CBG antibodies cross-react with CBGs in other birds, extending opportunities to study how CBG regulates the actions of glucocorticoids and sex steroids in these species. 27026706 4 15 from structures 577:586 arg1 complex 591:597 complex 591:597 complex with cortisol 591:611 Zebra finch and rat CBG crystal structures in complex with cortisol resemble each other, but their primary structures share only ∼40% identity, and their steroid-binding site topographies differ in several unexpected ways. 27026706 10 16 theme mRNA 1664:1667 arg1 Measurements 1644:1655 Measurements 1644:1655 Measurements of CBG mRNA in zebra finch tissues 1644:1690 Measurements of CBG mRNA in zebra finch tissues indicate that liver is the main site of plasma CBG production, and anti-zebra finch CBG antibodies cross-react with CBGs in other birds, extending opportunities to study how CBG regulates the actions of glucocorticoids and sex steroids in these species. 27026706 9 17 theme reactive 1536:1543 arg1 loop 1552:1555 its reactive center loop 1532:1555 its reactive center loop 1532:1555 As in mammals, a protease secreted by Pseudomonas aeruginosa cleaves CBG in zebra finch plasma within its reactive center loop and disrupts steroid binding, suggesting an evolutionarily conserved property of CBGs. 27026706 0 18 from Adaptations 111:121 arg1 Function 149:156 Function 149:156 Function 149:156 Identification of Avian Corticosteroid-binding Globulin (SerpinA6) Reveals the Molecular Basis of Evolutionary Adaptations in SerpinA6 Structure and Function as a Steroid-binding Protein. 27026706 0 18 from Adaptations 111:121 arg1 Structure 135:143 SerpinA6 Structure 126:143 SerpinA6 Structure 126:143 Identification of Avian Corticosteroid-binding Globulin (SerpinA6) Reveals the Molecular Basis of Evolutionary Adaptations in SerpinA6 Structure and Function as a Steroid-binding Protein. 27026706 4 19 theme several 743:749 arg1 ways 762:765 several unexpected ways 743:765 several unexpected ways 743:765 Zebra finch and rat CBG crystal structures in complex with cortisol resemble each other, but their primary structures share only ∼40% identity, and their steroid-binding site topographies differ in several unexpected ways. 27026706 0 20 theme Steroid-binding 163:177 arg1 Basis 89:93 the Molecular Basis 75:93 the Molecular Basis of Evolutionary Adaptations in SerpinA6 Structure and Function 75:156 Identification of Avian Corticosteroid-binding Globulin (SerpinA6) Reveals the Molecular Basis of Evolutionary Adaptations in SerpinA6 Structure and Function as a Steroid-binding Protein. 27026706 0 20 theme Steroid-binding 163:177 arg1 Protein 179:185 a Steroid-binding Protein 161:185 a Steroid-binding Protein 161:185 Identification of Avian Corticosteroid-binding Globulin (SerpinA6) Reveals the Molecular Basis of Evolutionary Adaptations in SerpinA6 Structure and Function as a Steroid-binding Protein. 27026706 4 21 theme site 715:718 arg1 topographies 720:731 their steroid-binding site topographies 693:731 their steroid-binding site topographies 693:731 Zebra finch and rat CBG crystal structures in complex with cortisol resemble each other, but their primary structures share only ∼40% identity, and their steroid-binding site topographies differ in several unexpected ways. 27026706 0 22 theme Molecular 79:87 arg1 Basis 89:93 the Molecular Basis 75:93 the Molecular Basis of Evolutionary Adaptations in SerpinA6 Structure and Function 75:156 Identification of Avian Corticosteroid-binding Globulin (SerpinA6) Reveals the Molecular Basis of Evolutionary Adaptations in SerpinA6 Structure and Function as a Steroid-binding Protein. 27026706 0 22 theme Molecular 79:87 arg1 Protein 179:185 a Steroid-binding Protein 161:185 a Steroid-binding Protein 161:185 Identification of Avian Corticosteroid-binding Globulin (SerpinA6) Reveals the Molecular Basis of Evolutionary Adaptations in SerpinA6 Structure and Function as a Steroid-binding Protein. 27026706 7 23 theme zebra 1010:1014 arg1 finch 1016:1020 zebra finch 1010:1020 zebra finch CBG 1010:1024 Glycosylation of this asparagine in zebra finch CBG does not influence its steroid-binding affinity, but we present evidence that it may participate in protein folding and steroid-binding site formation. 27026706 7 24 theme asparagine 996:1005 arg1 Glycosylation 974:986 Glycosylation 974:986 Glycosylation of this asparagine in zebra finch CBG 974:1024 Glycosylation of this asparagine in zebra finch CBG does not influence its steroid-binding affinity, but we present evidence that it may participate in protein folding and steroid-binding site formation. 27026706 10 25 theme main 1719:1722 arg1 liver 1706:1710 liver 1706:1710 liver 1706:1710 Measurements of CBG mRNA in zebra finch tissues indicate that liver is the main site of plasma CBG production, and anti-zebra finch CBG antibodies cross-react with CBGs in other birds, extending opportunities to study how CBG regulates the actions of glucocorticoids and sex steroids in these species. 27026706 10 25 theme main 1719:1722 arg1 production 1743:1752 plasma CBG production 1732:1752 plasma CBG production 1732:1752 Measurements of CBG mRNA in zebra finch tissues indicate that liver is the main site of plasma CBG production, and anti-zebra finch CBG antibodies cross-react with CBGs in other birds, extending opportunities to study how CBG regulates the actions of glucocorticoids and sex steroids in these species. 27026706 10 25 theme main 1719:1722 arg1 site 1724:1727 the main site 1715:1727 the main site of plasma CBG production 1715:1752 Measurements of CBG mRNA in zebra finch tissues indicate that liver is the main site of plasma CBG production, and anti-zebra finch CBG antibodies cross-react with CBGs in other birds, extending opportunities to study how CBG regulates the actions of glucocorticoids and sex steroids in these species. 27026706 0 26 theme Adaptations 111:121 arg1 Basis 89:93 the Molecular Basis 75:93 the Molecular Basis of Evolutionary Adaptations in SerpinA6 Structure and Function 75:156 Identification of Avian Corticosteroid-binding Globulin (SerpinA6) Reveals the Molecular Basis of Evolutionary Adaptations in SerpinA6 Structure and Function as a Steroid-binding Protein. 27026706 0 26 theme Adaptations 111:121 arg1 Protein 179:185 a Steroid-binding Protein 161:185 a Steroid-binding Protein 161:185 Identification of Avian Corticosteroid-binding Globulin (SerpinA6) Reveals the Molecular Basis of Evolutionary Adaptations in SerpinA6 Structure and Function as a Steroid-binding Protein. 27026706 3 27 theme steroid-binding 445:459 arg1 properties 461:470 Recombinant zebra finch CBG steroid-binding properties 417:470 Recombinant zebra finch CBG steroid-binding properties 417:470 Recombinant zebra finch CBG steroid-binding properties reflect those of the natural protein in plasma and confirm its identity. 27026706 5 28 theme steroid-binding 831:845 arg1 sites 847:851 mammalian CBG steroid-binding sites 817:851 mammalian CBG steroid-binding sites 817:851 Remarkably, a tryptophan that anchors ligands in mammalian CBG steroid-binding sites is replaced by an asparagine. 27026706 4 29 theme crystal 569:575 arg1 structures 577:586 Zebra finch and rat CBG crystal structures 545:586 Zebra finch and rat CBG crystal structures in complex with cortisol 545:611 Zebra finch and rat CBG crystal structures in complex with cortisol resemble each other, but their primary structures share only ∼40% identity, and their steroid-binding site topographies differ in several unexpected ways. 27026706 3 30 theme natural 493:499 arg1 protein 501:507 the natural protein 489:507 the natural protein in plasma 489:517 Recombinant zebra finch CBG steroid-binding properties reflect those of the natural protein in plasma and confirm its identity. 27026706 0 31 theme Avian 18:22 arg1 SerpinA6 57:64 SerpinA6 57:64 SerpinA6 57:64 Identification of Avian Corticosteroid-binding Globulin (SerpinA6) Reveals the Molecular Basis of Evolutionary Adaptations in SerpinA6 Structure and Function as a Steroid-binding Protein. 27026706 0 31 theme Avian 18:22 arg1 Globulin 47:54 Avian Corticosteroid-binding Globulin 18:54 Avian Corticosteroid-binding Globulin (SerpinA6) 18:65 Identification of Avian Corticosteroid-binding Globulin (SerpinA6) Reveals the Molecular Basis of Evolutionary Adaptations in SerpinA6 Structure and Function as a Steroid-binding Protein. 27026706 9 32 theme CBGs 1638:1641 arg1 property 1626:1633 an evolutionarily conserved property 1598:1633 an evolutionarily conserved property of CBGs 1598:1641 As in mammals, a protease secreted by Pseudomonas aeruginosa cleaves CBG in zebra finch plasma within its reactive center loop and disrupts steroid binding, suggesting an evolutionarily conserved property of CBGs. 27026706 3 33 theme finch 435:439 arg1 properties 461:470 Recombinant zebra finch CBG steroid-binding properties 417:470 Recombinant zebra finch CBG steroid-binding properties 417:470 Recombinant zebra finch CBG steroid-binding properties reflect those of the natural protein in plasma and confirm its identity. 27026706 0 34 theme Globulin 47:54 arg1 Identification 0:13 Identification 0:13 Identification of Avian Corticosteroid-binding Globulin (SerpinA6) 0:65 Identification of Avian Corticosteroid-binding Globulin (SerpinA6) Reveals the Molecular Basis of Evolutionary Adaptations in SerpinA6 Structure and Function as a Steroid-binding Protein. 27026706 6 35 theme Phylogenetic 883:894 arg1 comparisons 896:906 Phylogenetic comparisons 883:906 Phylogenetic comparisons 883:906 Phylogenetic comparisons show that reptilian CBG orthologs share this unexpected property. 27026706 3 36 theme Recombinant 417:427 arg1 finch 435:439 Recombinant zebra finch 417:439 Recombinant zebra finch CBG steroid-binding properties 417:470 Recombinant zebra finch CBG steroid-binding properties reflect those of the natural protein in plasma and confirm its identity. 27026706 4 37 theme finch 551:555 arg1 structures 577:586 Zebra finch and rat CBG crystal structures 545:586 Zebra finch and rat CBG crystal structures in complex with cortisol 545:611 Zebra finch and rat CBG crystal structures in complex with cortisol resemble each other, but their primary structures share only ∼40% identity, and their steroid-binding site topographies differ in several unexpected ways. 27026706 10 38 theme production 1743:1752 arg1 liver 1706:1710 liver 1706:1710 liver 1706:1710 Measurements of CBG mRNA in zebra finch tissues indicate that liver is the main site of plasma CBG production, and anti-zebra finch CBG antibodies cross-react with CBGs in other birds, extending opportunities to study how CBG regulates the actions of glucocorticoids and sex steroids in these species. 27026706 10 38 theme production 1743:1752 arg1 production 1743:1752 plasma CBG production 1732:1752 plasma CBG production 1732:1752 Measurements of CBG mRNA in zebra finch tissues indicate that liver is the main site of plasma CBG production, and anti-zebra finch CBG antibodies cross-react with CBGs in other birds, extending opportunities to study how CBG regulates the actions of glucocorticoids and sex steroids in these species. 27026706 10 38 theme production 1743:1752 arg1 site 1724:1727 the main site 1715:1727 the main site of plasma CBG production 1715:1752 Measurements of CBG mRNA in zebra finch tissues indicate that liver is the main site of plasma CBG production, and anti-zebra finch CBG antibodies cross-react with CBGs in other birds, extending opportunities to study how CBG regulates the actions of glucocorticoids and sex steroids in these species. 27026706 5 39 theme mammalian 817:825 arg1 sites 847:851 mammalian CBG steroid-binding sites 817:851 mammalian CBG steroid-binding sites 817:851 Remarkably, a tryptophan that anchors ligands in mammalian CBG steroid-binding sites is replaced by an asparagine. 27026706 4 40 theme rat 561:563 arg1 CBG 565:567 rat CBG 561:567 rat CBG 561:567 Zebra finch and rat CBG crystal structures in complex with cortisol resemble each other, but their primary structures share only ∼40% identity, and their steroid-binding site topographies differ in several unexpected ways. 27026706 10 41 theme steroids 1919:1926 arg1 actions 1884:1890 the actions 1880:1890 the actions of glucocorticoids and sex steroids 1880:1926 Measurements of CBG mRNA in zebra finch tissues indicate that liver is the main site of plasma CBG production, and anti-zebra finch CBG antibodies cross-react with CBGs in other birds, extending opportunities to study how CBG regulates the actions of glucocorticoids and sex steroids in these species. 27026706 3 42 from protein 501:507 arg1 plasma 512:517 plasma 512:517 plasma 512:517 Recombinant zebra finch CBG steroid-binding properties reflect those of the natural protein in plasma and confirm its identity. 27026706 10 43 theme plasma 1732:1737 arg1 production 1743:1752 plasma CBG production 1732:1752 plasma CBG production 1732:1752 Measurements of CBG mRNA in zebra finch tissues indicate that liver is the main site of plasma CBG production, and anti-zebra finch CBG antibodies cross-react with CBGs in other birds, extending opportunities to study how CBG regulates the actions of glucocorticoids and sex steroids in these species. 27026706 4 44 dep identity 679:686 arg1 % 677:677 % 677:677 % 677:677 Zebra finch and rat CBG crystal structures in complex with cortisol resemble each other, but their primary structures share only ∼40% identity, and their steroid-binding site topographies differ in several unexpected ways. 27026706 9 45 from CBG 1499:1501 arg1 plasma 1518:1523 zebra finch plasma 1506:1523 zebra finch plasma 1506:1523 As in mammals, a protease secreted by Pseudomonas aeruginosa cleaves CBG in zebra finch plasma within its reactive center loop and disrupts steroid binding, suggesting an evolutionarily conserved property of CBGs. 27026706 10 46 theme finch 1770:1774 arg1 antibodies 1780:1789 anti-zebra finch CBG antibodies 1759:1789 anti-zebra finch CBG antibodies 1759:1789 Measurements of CBG mRNA in zebra finch tissues indicate that liver is the main site of plasma CBG production, and anti-zebra finch CBG antibodies cross-react with CBGs in other birds, extending opportunities to study how CBG regulates the actions of glucocorticoids and sex steroids in these species. 27026706 10 47 from Measurements 1644:1655 arg1 tissues 1684:1690 zebra finch tissues 1672:1690 zebra finch tissues 1672:1690 Measurements of CBG mRNA in zebra finch tissues indicate that liver is the main site of plasma CBG production, and anti-zebra finch CBG antibodies cross-react with CBGs in other birds, extending opportunities to study how CBG regulates the actions of glucocorticoids and sex steroids in these species. 27026706 8 48 theme amino 1195:1199 arg1 acids 1201:1205 amino acids 1195:1205 amino acids within zebra finch CBG that are conserved only in birds 1195:1261 Substitutions of amino acids within zebra finch CBG that are conserved only in birds reveal how they contribute to their distinct steroid-binding properties, including their high (nanomolar) affinities for glucocorticoids, progesterone, and androgens. 27026706 7 49 theme steroid-binding 1146:1160 arg1 formation 1167:1175 steroid-binding site formation 1146:1175 steroid-binding site formation 1146:1175 Glycosylation of this asparagine in zebra finch CBG does not influence its steroid-binding affinity, but we present evidence that it may participate in protein folding and steroid-binding site formation. 27026706 4 50 with complex 591:597 arg1 cortisol 604:611 cortisol 604:611 cortisol 604:611 Zebra finch and rat CBG crystal structures in complex with cortisol resemble each other, but their primary structures share only ∼40% identity, and their steroid-binding site topographies differ in several unexpected ways. 27026706 1 51 theme mass 276:279 arg1 spectrometry 281:292 mass spectrometry 276:292 mass spectrometry 276:292 Corticosteroid-binding globulin (CBG) was isolated from chicken serum and identified by mass spectrometry and genomic analysis. 27026706 8 52 theme finch 1220:1224 arg1 CBG 1226:1228 zebra finch CBG 1214:1228 zebra finch CBG 1214:1228 Substitutions of amino acids within zebra finch CBG that are conserved only in birds reveal how they contribute to their distinct steroid-binding properties, including their high (nanomolar) affinities for glucocorticoids, progesterone, and androgens. 27026706 6 53 theme reptilian 918:926 arg1 orthologs 932:940 reptilian CBG orthologs 918:940 reptilian CBG orthologs 918:940 Phylogenetic comparisons show that reptilian CBG orthologs share this unexpected property. 27026706 10 54 theme CBG 1660:1662 arg1 mRNA 1664:1667 CBG mRNA 1660:1667 CBG mRNA 1660:1667 Measurements of CBG mRNA in zebra finch tissues indicate that liver is the main site of plasma CBG production, and anti-zebra finch CBG antibodies cross-react with CBGs in other birds, extending opportunities to study how CBG regulates the actions of glucocorticoids and sex steroids in these species. 27026706 9 55 theme zebra 1506:1510 arg1 finch 1512:1516 zebra finch 1506:1516 zebra finch plasma 1506:1523 As in mammals, a protease secreted by Pseudomonas aeruginosa cleaves CBG in zebra finch plasma within its reactive center loop and disrupts steroid binding, suggesting an evolutionarily conserved property of CBGs. 27026706 0 56 from Basis 89:93 arg1 Function 149:156 Function 149:156 Function 149:156 Identification of Avian Corticosteroid-binding Globulin (SerpinA6) Reveals the Molecular Basis of Evolutionary Adaptations in SerpinA6 Structure and Function as a Steroid-binding Protein. 27026706 0 56 from Basis 89:93 arg1 Structure 135:143 SerpinA6 Structure 126:143 SerpinA6 Structure 126:143 Identification of Avian Corticosteroid-binding Globulin (SerpinA6) Reveals the Molecular Basis of Evolutionary Adaptations in SerpinA6 Structure and Function as a Steroid-binding Protein. 27026706 8 57 theme distinct 1299:1306 arg1 affinities 1369:1378 their high (nanomolar) affinities 1346:1378 their high (nanomolar) affinities for glucocorticoids, progesterone, and androgens 1346:1427 Substitutions of amino acids within zebra finch CBG that are conserved only in birds reveal how they contribute to their distinct steroid-binding properties, including their high (nanomolar) affinities for glucocorticoids, progesterone, and androgens. 27026706 8 57 theme distinct 1299:1306 arg1 properties 1324:1333 their distinct steroid-binding properties 1293:1333 their distinct steroid-binding properties 1293:1333 Substitutions of amino acids within zebra finch CBG that are conserved only in birds reveal how they contribute to their distinct steroid-binding properties, including their high (nanomolar) affinities for glucocorticoids, progesterone, and androgens. 27026706 10 58 theme finch 1678:1682 arg1 tissues 1684:1690 zebra finch tissues 1672:1690 zebra finch tissues 1672:1690 Measurements of CBG mRNA in zebra finch tissues indicate that liver is the main site of plasma CBG production, and anti-zebra finch CBG antibodies cross-react with CBGs in other birds, extending opportunities to study how CBG regulates the actions of glucocorticoids and sex steroids in these species. 27026706 7 59 from Glycosylation 974:986 arg1 CBG 1022:1024 zebra finch CBG 1010:1024 zebra finch CBG 1010:1024 Glycosylation of this asparagine in zebra finch CBG does not influence its steroid-binding affinity, but we present evidence that it may participate in protein folding and steroid-binding site formation. 27026706 7 60 theme steroid-binding 1049:1063 arg1 affinity 1065:1072 its steroid-binding affinity 1045:1072 its steroid-binding affinity 1045:1072 Glycosylation of this asparagine in zebra finch CBG does not influence its steroid-binding affinity, but we present evidence that it may participate in protein folding and steroid-binding site formation. 27026706 9 61 theme center 1545:1550 arg1 loop 1552:1555 its reactive center loop 1532:1555 its reactive center loop 1532:1555 As in mammals, a protease secreted by Pseudomonas aeruginosa cleaves CBG in zebra finch plasma within its reactive center loop and disrupts steroid binding, suggesting an evolutionarily conserved property of CBGs. 27026706 8 62 theme high 1352:1355 arg1 affinities 1369:1378 their high (nanomolar) affinities 1346:1378 their high (nanomolar) affinities for glucocorticoids, progesterone, and androgens 1346:1427 Substitutions of amino acids within zebra finch CBG that are conserved only in birds reveal how they contribute to their distinct steroid-binding properties, including their high (nanomolar) affinities for glucocorticoids, progesterone, and androgens. 27026706 8 63 theme nanomolar 1358:1366 arg1 affinities 1369:1378 their high (nanomolar) affinities 1346:1378 their high (nanomolar) affinities for glucocorticoids, progesterone, and androgens 1346:1427 Substitutions of amino acids within zebra finch CBG that are conserved only in birds reveal how they contribute to their distinct steroid-binding properties, including their high (nanomolar) affinities for glucocorticoids, progesterone, and androgens. 27026706 9 64 theme steroid 1570:1576 arg1 binding 1578:1584 steroid binding 1570:1584 steroid binding 1570:1584 As in mammals, a protease secreted by Pseudomonas aeruginosa cleaves CBG in zebra finch plasma within its reactive center loop and disrupts steroid binding, suggesting an evolutionarily conserved property of CBGs. 27026706 10 65 from CBGs 1808:1811 arg1 birds 1822:1826 other birds 1816:1826 other birds 1816:1826 Measurements of CBG mRNA in zebra finch tissues indicate that liver is the main site of plasma CBG production, and anti-zebra finch CBG antibodies cross-react with CBGs in other birds, extending opportunities to study how CBG regulates the actions of glucocorticoids and sex steroids in these species. 27026706 4 66 theme Zebra 545:549 arg1 finch 551:555 Zebra finch 545:555 Zebra finch 545:555 Zebra finch and rat CBG crystal structures in complex with cortisol resemble each other, but their primary structures share only ∼40% identity, and their steroid-binding site topographies differ in several unexpected ways. 27026706 1 67 attach isolated 230:237 arg1 serum 252:256 chicken serum 244:256 chicken serum 244:256 Corticosteroid-binding globulin (CBG) was isolated from chicken serum and identified by mass spectrometry and genomic analysis. 27026706 1 67 attach isolated 230:237 arg2 CBG 221:223 CBG 221:223 CBG 221:223 Corticosteroid-binding globulin (CBG) was isolated from chicken serum and identified by mass spectrometry and genomic analysis. 27026706 1 67 attach isolated 230:237 arg2 globulin 211:218 Corticosteroid-binding globulin 188:218 Corticosteroid-binding globulin (CBG) 188:224 Corticosteroid-binding globulin (CBG) was isolated from chicken serum and identified by mass spectrometry and genomic analysis. 27026706 4 68 theme steroid-binding 699:713 arg1 topographies 720:731 their steroid-binding site topographies 693:731 their steroid-binding site topographies 693:731 Zebra finch and rat CBG crystal structures in complex with cortisol resemble each other, but their primary structures share only ∼40% identity, and their steroid-binding site topographies differ in several unexpected ways. 27026706 0 69 theme Evolutionary 98:109 arg1 Adaptations 111:121 Evolutionary Adaptations 98:121 Evolutionary Adaptations in SerpinA6 Structure and Function 98:156 Identification of Avian Corticosteroid-binding Globulin (SerpinA6) Reveals the Molecular Basis of Evolutionary Adaptations in SerpinA6 Structure and Function as a Steroid-binding Protein. 27026706 5 70 from ligands 806:812 arg1 sites 847:851 mammalian CBG steroid-binding sites 817:851 mammalian CBG steroid-binding sites 817:851 Remarkably, a tryptophan that anchors ligands in mammalian CBG steroid-binding sites is replaced by an asparagine. 27026706 7 71 theme finch 1016:1020 arg1 CBG 1022:1024 zebra finch CBG 1010:1024 zebra finch CBG 1010:1024 Glycosylation of this asparagine in zebra finch CBG does not influence its steroid-binding affinity, but we present evidence that it may participate in protein folding and steroid-binding site formation. 27026706 4 72 theme primary 644:650 arg1 structures 652:661 their primary structures 638:661 their primary structures 638:661 Zebra finch and rat CBG crystal structures in complex with cortisol resemble each other, but their primary structures share only ∼40% identity, and their steroid-binding site topographies differ in several unexpected ways. 27026706 5 73 theme CBG 827:829 arg1 sites 847:851 mammalian CBG steroid-binding sites 817:851 mammalian CBG steroid-binding sites 817:851 Remarkably, a tryptophan that anchors ligands in mammalian CBG steroid-binding sites is replaced by an asparagine. 27026706 9 74 theme conserved 1616:1624 arg1 property 1626:1633 an evolutionarily conserved property 1598:1633 an evolutionarily conserved property of CBGs 1598:1641 As in mammals, a protease secreted by Pseudomonas aeruginosa cleaves CBG in zebra finch plasma within its reactive center loop and disrupts steroid binding, suggesting an evolutionarily conserved property of CBGs. 27026706 4 75 theme unexpected 751:760 arg1 ways 762:765 several unexpected ways 743:765 several unexpected ways 743:765 Zebra finch and rat CBG crystal structures in complex with cortisol resemble each other, but their primary structures share only ∼40% identity, and their steroid-binding site topographies differ in several unexpected ways. 27026706 2 76 theme genes 396:400 arg1 synteny 356:362 synteny 356:362 synteny 356:362 This revealed that the organization and synteny of avian and mammalian SerpinA6 genes are conserved. 27026706 2 76 theme genes 396:400 arg1 organization 339:350 organization 339:350 organization 339:350 This revealed that the organization and synteny of avian and mammalian SerpinA6 genes are conserved. 27026706 0 77 theme Corticosteroid-binding 24:45 arg1 SerpinA6 57:64 SerpinA6 57:64 SerpinA6 57:64 Identification of Avian Corticosteroid-binding Globulin (SerpinA6) Reveals the Molecular Basis of Evolutionary Adaptations in SerpinA6 Structure and Function as a Steroid-binding Protein. 27026706 0 77 theme Corticosteroid-binding 24:45 arg1 Globulin 47:54 Avian Corticosteroid-binding Globulin 18:54 Avian Corticosteroid-binding Globulin (SerpinA6) 18:65 Identification of Avian Corticosteroid-binding Globulin (SerpinA6) Reveals the Molecular Basis of Evolutionary Adaptations in SerpinA6 Structure and Function as a Steroid-binding Protein. 27026706 1 78 theme genomic 298:304 arg1 analysis 306:313 genomic analysis 298:313 genomic analysis 298:313 Corticosteroid-binding globulin (CBG) was isolated from chicken serum and identified by mass spectrometry and genomic analysis. 27026706 10 79 theme glucocorticoids 1895:1909 arg1 actions 1884:1890 the actions 1880:1890 the actions of glucocorticoids and sex steroids 1880:1926 Measurements of CBG mRNA in zebra finch tissues indicate that liver is the main site of plasma CBG production, and anti-zebra finch CBG antibodies cross-react with CBGs in other birds, extending opportunities to study how CBG regulates the actions of glucocorticoids and sex steroids in these species. 27026706 2 80 theme SerpinA6 387:394 arg1 genes 396:400 avian and mammalian SerpinA6 genes 367:400 avian and mammalian SerpinA6 genes 367:400 This revealed that the organization and synteny of avian and mammalian SerpinA6 genes are conserved. 27026706 3 81 theme CBG 441:443 arg1 properties 461:470 Recombinant zebra finch CBG steroid-binding properties 417:470 Recombinant zebra finch CBG steroid-binding properties 417:470 Recombinant zebra finch CBG steroid-binding properties reflect those of the natural protein in plasma and confirm its identity. 27026706 0 82 from Structure 135:143 arg1 Basis 89:93 the Molecular Basis 75:93 the Molecular Basis of Evolutionary Adaptations in SerpinA6 Structure and Function 75:156 Identification of Avian Corticosteroid-binding Globulin (SerpinA6) Reveals the Molecular Basis of Evolutionary Adaptations in SerpinA6 Structure and Function as a Steroid-binding Protein. 27026706 0 82 from Structure 135:143 arg1 Protein 179:185 a Steroid-binding Protein 161:185 a Steroid-binding Protein 161:185 Identification of Avian Corticosteroid-binding Globulin (SerpinA6) Reveals the Molecular Basis of Evolutionary Adaptations in SerpinA6 Structure and Function as a Steroid-binding Protein. 27026706 3 83 theme zebra 429:433 arg1 finch 435:439 Recombinant zebra finch 417:439 Recombinant zebra finch CBG steroid-binding properties 417:470 Recombinant zebra finch CBG steroid-binding properties reflect those of the natural protein in plasma and confirm its identity. 27026706 4 84 theme CBG 565:567 arg1 structures 577:586 Zebra finch and rat CBG crystal structures 545:586 Zebra finch and rat CBG crystal structures in complex with cortisol 545:611 Zebra finch and rat CBG crystal structures in complex with cortisol resemble each other, but their primary structures share only ∼40% identity, and their steroid-binding site topographies differ in several unexpected ways. 27026706 10 85 theme CBG 1739:1741 arg1 production 1743:1752 plasma CBG production 1732:1752 plasma CBG production 1732:1752 Measurements of CBG mRNA in zebra finch tissues indicate that liver is the main site of plasma CBG production, and anti-zebra finch CBG antibodies cross-react with CBGs in other birds, extending opportunities to study how CBG regulates the actions of glucocorticoids and sex steroids in these species. 27026706 0 86 from Function 149:156 arg1 Basis 89:93 the Molecular Basis 75:93 the Molecular Basis of Evolutionary Adaptations in SerpinA6 Structure and Function 75:156 Identification of Avian Corticosteroid-binding Globulin (SerpinA6) Reveals the Molecular Basis of Evolutionary Adaptations in SerpinA6 Structure and Function as a Steroid-binding Protein. 27026706 0 86 from Function 149:156 arg1 Protein 179:185 a Steroid-binding Protein 161:185 a Steroid-binding Protein 161:185 Identification of Avian Corticosteroid-binding Globulin (SerpinA6) Reveals the Molecular Basis of Evolutionary Adaptations in SerpinA6 Structure and Function as a Steroid-binding Protein. 27026706 10 87 theme sex 1915:1917 arg1 steroids 1919:1926 sex steroids 1915:1926 sex steroids 1915:1926 Measurements of CBG mRNA in zebra finch tissues indicate that liver is the main site of plasma CBG production, and anti-zebra finch CBG antibodies cross-react with CBGs in other birds, extending opportunities to study how CBG regulates the actions of glucocorticoids and sex steroids in these species. 27026706 10 88 theme anti-zebra 1759:1768 arg1 antibodies 1780:1789 anti-zebra finch CBG antibodies 1759:1789 anti-zebra finch CBG antibodies 1759:1789 Measurements of CBG mRNA in zebra finch tissues indicate that liver is the main site of plasma CBG production, and anti-zebra finch CBG antibodies cross-react with CBGs in other birds, extending opportunities to study how CBG regulates the actions of glucocorticoids and sex steroids in these species. 27026706 1 89 theme chicken 244:250 arg1 serum 252:256 chicken serum 244:256 chicken serum 244:256 Corticosteroid-binding globulin (CBG) was isolated from chicken serum and identified by mass spectrometry and genomic analysis. 27026706 4 90 dep % 677:677 arg1 ∼40 674:676 ∼40 674:676 ∼40 674:676 Zebra finch and rat CBG crystal structures in complex with cortisol resemble each other, but their primary structures share only ∼40% identity, and their steroid-binding site topographies differ in several unexpected ways. 27026706 7 91 gly Glycosylation 974:986 arg1 asparagine 996:1005 this asparagine 991:1005 this asparagine 991:1005 Glycosylation of this asparagine in zebra finch CBG does not influence its steroid-binding affinity, but we present evidence that it may participate in protein folding and steroid-binding site formation. 27026706 2 92 theme mammalian 377:385 arg1 genes 396:400 avian and mammalian SerpinA6 genes 367:400 avian and mammalian SerpinA6 genes 367:400 This revealed that the organization and synteny of avian and mammalian SerpinA6 genes are conserved. 26840030 10 0 theme PKA-CREB 1546:1553 arg1 signaling 1555:1563 PKA-CREB signaling 1546:1563 PKA-CREB signaling 1546:1563 Downregulation of O-GlcNAcylation suppresses PKA-CREB signaling and consequently causes learning and memory deficits in AD. 26840030 8 1 from Reduction 1114:1122 arg1 O-GlcNAcylation 1127:1141 O-GlcNAcylation 1127:1141 O-GlcNAcylation 1127:1141 Reduction in O-GlcNAcylation through intracerebroventricular injection of 6-diazo-5-oxo-l-norleucine (DON), the inhibitor of glutamine fructose-6-phosphate amidotransferase, suppressed PKA-CREB signaling and impaired learning and memory in mice. 26840030 5 2 theme PKAcα 597:601 arg1 location 585:592 the subcellular location 569:592 the subcellular location of PKAcα and PKAcβ 569:611 O-GlcNAcylation regulated the subcellular location of PKAcα and PKAcβ and enhanced their kinase activity. 26840030 4 3 theme catalytic 438:446 arg1 PKAcs 458:462 PKAcs 458:462 PKAcs 458:462 In this study, we found that PKA catalytic subunits (PKAcs) were posttranslationally modified by O-linked N-acetylglucosamine (O-GlcNAc). 26840030 4 3 theme catalytic 438:446 arg1 subunits 448:455 PKA catalytic subunits 434:455 PKA catalytic subunits (PKAcs) 434:463 In this study, we found that PKA catalytic subunits (PKAcs) were posttranslationally modified by O-linked N-acetylglucosamine (O-GlcNAc). 26840030 8 4 theme intracerebroventricular 1151:1173 arg1 injection 1175:1183 intracerebroventricular injection 1151:1183 intracerebroventricular injection of 6-diazo-5-oxo-l-norleucine (DON), the inhibitor of glutamine fructose-6-phosphate amidotransferase, 1151:1286 Reduction in O-GlcNAcylation through intracerebroventricular injection of 6-diazo-5-oxo-l-norleucine (DON), the inhibitor of glutamine fructose-6-phosphate amidotransferase, suppressed PKA-CREB signaling and impaired learning and memory in mice. 26840030 7 5 theme O-GlcNAcylation 999:1013 arg1 downregulation 981:994 downregulation 981:994 downregulation of O-GlcNAcylation 981:1013 In contrast, in rat and mouse brains, downregulation of O-GlcNAcylation caused decreases in the phosphorylation of CREB at Ser133 and of tau at Ser214, but not at Thr205. 26840030 4 6 theme O-linked 502:509 arg1 O-GlcNAc 532:539 O-GlcNAc 532:539 O-GlcNAc 532:539 In this study, we found that PKA catalytic subunits (PKAcs) were posttranslationally modified by O-linked N-acetylglucosamine (O-GlcNAc). 26840030 4 6 theme O-linked 502:509 arg1 N-acetylglucosamine 511:529 O-linked N-acetylglucosamine 502:529 O-linked N-acetylglucosamine (O-GlcNAc) 502:540 In this study, we found that PKA catalytic subunits (PKAcs) were posttranslationally modified by O-linked N-acetylglucosamine (O-GlcNAc). 26840030 4 7 theme PKA 434:436 arg1 PKAcs 458:462 PKAcs 458:462 PKAcs 458:462 In this study, we found that PKA catalytic subunits (PKAcs) were posttranslationally modified by O-linked N-acetylglucosamine (O-GlcNAc). 26840030 4 7 theme PKA 434:436 arg1 subunits 448:455 PKA catalytic subunits 434:455 PKA catalytic subunits (PKAcs) 434:463 In this study, we found that PKA catalytic subunits (PKAcs) were posttranslationally modified by O-linked N-acetylglucosamine (O-GlcNAc). 26840030 5 8 theme PKAcβ 607:611 arg1 location 585:592 the subcellular location 569:592 the subcellular location of PKAcα and PKAcβ 569:611 O-GlcNAcylation regulated the subcellular location of PKAcα and PKAcβ and enhanced their kinase activity. 26840030 0 9 dep learning 100:107 arg1 deficits 120:127 deficits 120:127 deficits 120:127 O-GlcNAcylation of protein kinase A catalytic subunits enhances its activity: a mechanism linked to learning and memory deficits in Alzheimer's disease. 26840030 8 10 from memory 1344:1349 arg1 mice 1354:1357 mice 1354:1357 mice 1354:1357 Reduction in O-GlcNAcylation through intracerebroventricular injection of 6-diazo-5-oxo-l-norleucine (DON), the inhibitor of glutamine fructose-6-phosphate amidotransferase, suppressed PKA-CREB signaling and impaired learning and memory in mice. 26840030 7 11 theme rat 959:961 arg1 brains 973:978 rat and mouse brains 959:978 rat and mouse brains 959:978 In contrast, in rat and mouse brains, downregulation of O-GlcNAcylation caused decreases in the phosphorylation of CREB at Ser133 and of tau at Ser214, but not at Thr205. 26840030 2 12 theme A 259:259 arg1 signaling 272:280 Protein kinase A (PKA)-CREB signaling 244:280 Protein kinase A (PKA)-CREB signaling 244:280 Protein kinase A (PKA)-CREB signaling plays a critical role in learning and memory. 26840030 6 13 theme O-GlcNAcylation 665:679 arg1 Upregulation 649:660 Upregulation 649:660 Upregulation of O-GlcNAcylation in metabolically active rat brain slices by O-(2-acetamido-2-deoxy-d-glucopyranosylidenamino) N-phenylcarbamate (PUGNAc), an inhibitor of N-acetylglucosaminidase, 649:842 Upregulation of O-GlcNAcylation in metabolically active rat brain slices by O-(2-acetamido-2-deoxy-d-glucopyranosylidenamino) N-phenylcarbamate (PUGNAc), an inhibitor of N-acetylglucosaminidase, increased the phosphorylation of tau at the PKA site, Ser214, but not at the non-PKA site, Thr205. 26840030 7 14 from decreases 1022:1030 arg1 phosphorylation 1039:1053 the phosphorylation 1035:1053 the phosphorylation of CREB at Ser133 1035:1071 In contrast, in rat and mouse brains, downregulation of O-GlcNAcylation caused decreases in the phosphorylation of CREB at Ser133 and of tau at Ser214, but not at Thr205. 26840030 7 14 from decreases 1022:1030 arg1 Ser133 1066:1071 Ser133 1066:1071 Ser133 1066:1071 In contrast, in rat and mouse brains, downregulation of O-GlcNAcylation caused decreases in the phosphorylation of CREB at Ser133 and of tau at Ser214, but not at Thr205. 26840030 8 15 theme glutamine 1239:1247 arg1 6-diazo-5-oxo-l-norleucine 1188:1213 6-diazo-5-oxo-l-norleucine 1188:1213 6-diazo-5-oxo-l-norleucine (DON) 1188:1219 Reduction in O-GlcNAcylation through intracerebroventricular injection of 6-diazo-5-oxo-l-norleucine (DON), the inhibitor of glutamine fructose-6-phosphate amidotransferase, suppressed PKA-CREB signaling and impaired learning and memory in mice. 26840030 8 15 theme glutamine 1239:1247 arg1 inhibitor 1226:1234 the inhibitor 1222:1234 the inhibitor of glutamine fructose-6-phosphate amidotransferase 1222:1285 Reduction in O-GlcNAcylation through intracerebroventricular injection of 6-diazo-5-oxo-l-norleucine (DON), the inhibitor of glutamine fructose-6-phosphate amidotransferase, suppressed PKA-CREB signaling and impaired learning and memory in mice. 26840030 2 16 theme kinase 252:257 arg1 A 259:259 Protein kinase A 244:259 Protein kinase A (PKA)-CREB signaling 244:280 Protein kinase A (PKA)-CREB signaling plays a critical role in learning and memory. 26840030 2 16 theme kinase 252:257 arg1 PKA 262:264 PKA 262:264 PKA 262:264 Protein kinase A (PKA)-CREB signaling plays a critical role in learning and memory. 26840030 8 17 theme 6-diazo-5-oxo-l-norleucine 1188:1213 arg1 injection 1175:1183 intracerebroventricular injection 1151:1183 intracerebroventricular injection of 6-diazo-5-oxo-l-norleucine (DON), the inhibitor of glutamine fructose-6-phosphate amidotransferase, 1151:1286 Reduction in O-GlcNAcylation through intracerebroventricular injection of 6-diazo-5-oxo-l-norleucine (DON), the inhibitor of glutamine fructose-6-phosphate amidotransferase, suppressed PKA-CREB signaling and impaired learning and memory in mice. 26840030 0 18 theme subunits 46:53 arg1 O-GlcNAcylation 0:14 O-GlcNAcylation 0:14 O-GlcNAcylation of protein kinase A catalytic subunits 0:53 O-GlcNAcylation of protein kinase A catalytic subunits enhances its activity: a mechanism linked to learning and memory deficits in Alzheimer's disease. 26840030 6 19 theme tau 877:879 arg1 phosphorylation 858:872 the phosphorylation 854:872 the phosphorylation of tau 854:879 Upregulation of O-GlcNAcylation in metabolically active rat brain slices by O-(2-acetamido-2-deoxy-d-glucopyranosylidenamino) N-phenylcarbamate (PUGNAc), an inhibitor of N-acetylglucosaminidase, increased the phosphorylation of tau at the PKA site, Ser214, but not at the non-PKA site, Thr205. 26840030 4 20 mod modified 490:497 arg1 PKAcs 458:462 PKAcs 458:462 PKAcs 458:462 In this study, we found that PKA catalytic subunits (PKAcs) were posttranslationally modified by O-linked N-acetylglucosamine (O-GlcNAc). 26840030 4 20 mod modified 490:497 arg1 subunits 448:455 PKA catalytic subunits 434:455 PKA catalytic subunits (PKAcs) 434:463 In this study, we found that PKA catalytic subunits (PKAcs) were posttranslationally modified by O-linked N-acetylglucosamine (O-GlcNAc). 26840030 4 20 mod modified 490:497 arg3 N-acetylglucosamine 511:529 O-linked N-acetylglucosamine 502:529 O-linked N-acetylglucosamine (O-GlcNAc) 502:540 In this study, we found that PKA catalytic subunits (PKAcs) were posttranslationally modified by O-linked N-acetylglucosamine (O-GlcNAc). 26840030 4 20 mod modified 490:497 arg3 O-GlcNAc 532:539 O-GlcNAc 532:539 O-GlcNAc 532:539 In this study, we found that PKA catalytic subunits (PKAcs) were posttranslationally modified by O-linked N-acetylglucosamine (O-GlcNAc). 26840030 2 21 theme Protein 244:250 arg1 A 259:259 Protein kinase A 244:259 Protein kinase A (PKA)-CREB signaling 244:280 Protein kinase A (PKA)-CREB signaling plays a critical role in learning and memory. 26840030 2 21 theme Protein 244:250 arg1 PKA 262:264 PKA 262:264 PKA 262:264 Protein kinase A (PKA)-CREB signaling plays a critical role in learning and memory. 26840030 6 22 theme 2-acetamido-2-deoxy-d-glucopyranosylidenamino 728:772 arg1 PUGNAc 794:799 PUGNAc 794:799 PUGNAc 794:799 Upregulation of O-GlcNAcylation in metabolically active rat brain slices by O-(2-acetamido-2-deoxy-d-glucopyranosylidenamino) N-phenylcarbamate (PUGNAc), an inhibitor of N-acetylglucosaminidase, increased the phosphorylation of tau at the PKA site, Ser214, but not at the non-PKA site, Thr205. 26840030 6 22 theme 2-acetamido-2-deoxy-d-glucopyranosylidenamino 728:772 arg1 N-phenylcarbamate 775:791 O-(2-acetamido-2-deoxy-d-glucopyranosylidenamino) N-phenylcarbamate 725:791 O-(2-acetamido-2-deoxy-d-glucopyranosylidenamino) N-phenylcarbamate (PUGNAc) 725:800 Upregulation of O-GlcNAcylation in metabolically active rat brain slices by O-(2-acetamido-2-deoxy-d-glucopyranosylidenamino) N-phenylcarbamate (PUGNAc), an inhibitor of N-acetylglucosaminidase, increased the phosphorylation of tau at the PKA site, Ser214, but not at the non-PKA site, Thr205. 26840030 6 22 theme 2-acetamido-2-deoxy-d-glucopyranosylidenamino 728:772 arg1 inhibitor 806:814 an inhibitor 803:814 an inhibitor of N-acetylglucosaminidase 803:841 Upregulation of O-GlcNAcylation in metabolically active rat brain slices by O-(2-acetamido-2-deoxy-d-glucopyranosylidenamino) N-phenylcarbamate (PUGNAc), an inhibitor of N-acetylglucosaminidase, increased the phosphorylation of tau at the PKA site, Ser214, but not at the non-PKA site, Thr205. 26840030 2 23 theme -CREB 266:270 arg1 signaling 272:280 Protein kinase A (PKA)-CREB signaling 244:280 Protein kinase A (PKA)-CREB signaling 244:280 Protein kinase A (PKA)-CREB signaling plays a critical role in learning and memory. 26840030 0 24 theme kinase 27:32 arg1 A 34:34 protein kinase A 19:34 protein kinase A catalytic subunits 19:53 O-GlcNAcylation of protein kinase A catalytic subunits enhances its activity: a mechanism linked to learning and memory deficits in Alzheimer's disease. 26840030 8 25 theme fructose-6-phosphate 1249:1268 arg1 amidotransferase 1270:1285 fructose-6-phosphate amidotransferase 1249:1285 glutamine fructose-6-phosphate amidotransferase 1239:1285 Reduction in O-GlcNAcylation through intracerebroventricular injection of 6-diazo-5-oxo-l-norleucine (DON), the inhibitor of glutamine fructose-6-phosphate amidotransferase, suppressed PKA-CREB signaling and impaired learning and memory in mice. 26840030 6 26 theme PKA 888:890 arg1 site 892:895 the PKA site 884:895 the PKA site 884:895 Upregulation of O-GlcNAcylation in metabolically active rat brain slices by O-(2-acetamido-2-deoxy-d-glucopyranosylidenamino) N-phenylcarbamate (PUGNAc), an inhibitor of N-acetylglucosaminidase, increased the phosphorylation of tau at the PKA site, Ser214, but not at the non-PKA site, Thr205. 26840030 6 26 theme PKA 888:890 arg1 Ser214 898:903 Ser214 898:903 Ser214 898:903 Upregulation of O-GlcNAcylation in metabolically active rat brain slices by O-(2-acetamido-2-deoxy-d-glucopyranosylidenamino) N-phenylcarbamate (PUGNAc), an inhibitor of N-acetylglucosaminidase, increased the phosphorylation of tau at the PKA site, Ser214, but not at the non-PKA site, Thr205. 26840030 0 27 theme protein 19:25 arg1 A 34:34 protein kinase A 19:34 protein kinase A catalytic subunits 19:53 O-GlcNAcylation of protein kinase A catalytic subunits enhances its activity: a mechanism linked to learning and memory deficits in Alzheimer's disease. 26840030 6 28 theme non-PKA 921:927 arg1 Thr205 935:940 Thr205 935:940 Thr205 935:940 Upregulation of O-GlcNAcylation in metabolically active rat brain slices by O-(2-acetamido-2-deoxy-d-glucopyranosylidenamino) N-phenylcarbamate (PUGNAc), an inhibitor of N-acetylglucosaminidase, increased the phosphorylation of tau at the PKA site, Ser214, but not at the non-PKA site, Thr205. 26840030 6 28 theme non-PKA 921:927 arg1 site 929:932 the non-PKA site 917:932 the non-PKA site 917:932 Upregulation of O-GlcNAcylation in metabolically active rat brain slices by O-(2-acetamido-2-deoxy-d-glucopyranosylidenamino) N-phenylcarbamate (PUGNAc), an inhibitor of N-acetylglucosaminidase, increased the phosphorylation of tau at the PKA site, Ser214, but not at the non-PKA site, Thr205. 26840030 6 29 from O-GlcNAcylation 665:679 arg1 slices 715:720 metabolically active rat brain slices 684:720 metabolically active rat brain slices 684:720 Upregulation of O-GlcNAcylation in metabolically active rat brain slices by O-(2-acetamido-2-deoxy-d-glucopyranosylidenamino) N-phenylcarbamate (PUGNAc), an inhibitor of N-acetylglucosaminidase, increased the phosphorylation of tau at the PKA site, Ser214, but not at the non-PKA site, Thr205. 26840030 8 30 theme PKA-CREB 1299:1306 arg1 signaling 1308:1316 PKA-CREB signaling 1299:1316 PKA-CREB signaling 1299:1316 Reduction in O-GlcNAcylation through intracerebroventricular injection of 6-diazo-5-oxo-l-norleucine (DON), the inhibitor of glutamine fructose-6-phosphate amidotransferase, suppressed PKA-CREB signaling and impaired learning and memory in mice. 26840030 0 31 theme catalytic 36:44 arg1 subunits 46:53 protein kinase A catalytic subunits 19:53 protein kinase A catalytic subunits 19:53 O-GlcNAcylation of protein kinase A catalytic subunits enhances its activity: a mechanism linked to learning and memory deficits in Alzheimer's disease. 26840030 9 32 theme novel 1450:1454 arg1 O-GlcNAcylation 1429:1443 O-GlcNAcylation 1429:1443 O-GlcNAcylation 1429:1443 These results indicate that in addition to cAMP and phosphorylation, O-GlcNAcylation is a novel mechanism that regulates PKA-CREB signaling. 26840030 9 32 theme novel 1450:1454 arg1 mechanism 1456:1464 a novel mechanism 1448:1464 a novel mechanism that regulates PKA-CREB signaling 1448:1498 These results indicate that in addition to cAMP and phosphorylation, O-GlcNAcylation is a novel mechanism that regulates PKA-CREB signaling. 26840030 3 33 theme AD 395:396 arg1 brain 398:402 AD brain 395:402 AD brain 395:402 It is known that glucose uptake and O-GlcNAcylation are reduced in AD brain. 26840030 0 34 theme A 34:34 arg1 subunits 46:53 protein kinase A catalytic subunits 19:53 protein kinase A catalytic subunits 19:53 O-GlcNAcylation of protein kinase A catalytic subunits enhances its activity: a mechanism linked to learning and memory deficits in Alzheimer's disease. 26840030 1 35 theme cognitive 225:233 arg1 decline 235:241 cognitive decline 225:241 cognitive decline 225:241 Alzheimer's disease (AD) is characterized clinically by memory loss and cognitive decline. 26840030 6 36 theme O- 725:726 arg1 PUGNAc 794:799 PUGNAc 794:799 PUGNAc 794:799 Upregulation of O-GlcNAcylation in metabolically active rat brain slices by O-(2-acetamido-2-deoxy-d-glucopyranosylidenamino) N-phenylcarbamate (PUGNAc), an inhibitor of N-acetylglucosaminidase, increased the phosphorylation of tau at the PKA site, Ser214, but not at the non-PKA site, Thr205. 26840030 6 36 theme O- 725:726 arg1 N-phenylcarbamate 775:791 O-(2-acetamido-2-deoxy-d-glucopyranosylidenamino) N-phenylcarbamate 725:791 O-(2-acetamido-2-deoxy-d-glucopyranosylidenamino) N-phenylcarbamate (PUGNAc) 725:800 Upregulation of O-GlcNAcylation in metabolically active rat brain slices by O-(2-acetamido-2-deoxy-d-glucopyranosylidenamino) N-phenylcarbamate (PUGNAc), an inhibitor of N-acetylglucosaminidase, increased the phosphorylation of tau at the PKA site, Ser214, but not at the non-PKA site, Thr205. 26840030 6 36 theme O- 725:726 arg1 inhibitor 806:814 an inhibitor 803:814 an inhibitor of N-acetylglucosaminidase 803:841 Upregulation of O-GlcNAcylation in metabolically active rat brain slices by O-(2-acetamido-2-deoxy-d-glucopyranosylidenamino) N-phenylcarbamate (PUGNAc), an inhibitor of N-acetylglucosaminidase, increased the phosphorylation of tau at the PKA site, Ser214, but not at the non-PKA site, Thr205. 26840030 6 37 theme active 698:703 arg1 slices 715:720 metabolically active rat brain slices 684:720 metabolically active rat brain slices 684:720 Upregulation of O-GlcNAcylation in metabolically active rat brain slices by O-(2-acetamido-2-deoxy-d-glucopyranosylidenamino) N-phenylcarbamate (PUGNAc), an inhibitor of N-acetylglucosaminidase, increased the phosphorylation of tau at the PKA site, Ser214, but not at the non-PKA site, Thr205. 26840030 10 38 theme O-GlcNAcylation 1519:1533 arg1 Downregulation 1501:1514 Downregulation 1501:1514 Downregulation of O-GlcNAcylation 1501:1533 Downregulation of O-GlcNAcylation suppresses PKA-CREB signaling and consequently causes learning and memory deficits in AD. 26840030 7 39 theme mouse 967:971 arg1 brains 973:978 rat and mouse brains 959:978 rat and mouse brains 959:978 In contrast, in rat and mouse brains, downregulation of O-GlcNAcylation caused decreases in the phosphorylation of CREB at Ser133 and of tau at Ser214, but not at Thr205. 26840030 6 40 from slices 715:720 arg1 Upregulation 649:660 Upregulation 649:660 Upregulation of O-GlcNAcylation in metabolically active rat brain slices by O-(2-acetamido-2-deoxy-d-glucopyranosylidenamino) N-phenylcarbamate (PUGNAc), an inhibitor of N-acetylglucosaminidase, 649:842 Upregulation of O-GlcNAcylation in metabolically active rat brain slices by O-(2-acetamido-2-deoxy-d-glucopyranosylidenamino) N-phenylcarbamate (PUGNAc), an inhibitor of N-acetylglucosaminidase, increased the phosphorylation of tau at the PKA site, Ser214, but not at the non-PKA site, Thr205. 26840030 3 41 theme glucose 345:351 arg1 uptake 353:358 glucose uptake 345:358 glucose uptake 345:358 It is known that glucose uptake and O-GlcNAcylation are reduced in AD brain. 26840030 7 42 from Ser133 1066:1071 arg1 phosphorylation 1039:1053 the phosphorylation 1035:1053 the phosphorylation of CREB at Ser133 1035:1071 In contrast, in rat and mouse brains, downregulation of O-GlcNAcylation caused decreases in the phosphorylation of CREB at Ser133 and of tau at Ser214, but not at Thr205. 26840030 7 42 from Ser133 1066:1071 arg1 decreases 1022:1030 decreases 1022:1030 decreases in the phosphorylation of CREB at Ser133 and of tau 1022:1082 In contrast, in rat and mouse brains, downregulation of O-GlcNAcylation caused decreases in the phosphorylation of CREB at Ser133 and of tau at Ser214, but not at Thr205. 26840030 6 43 theme N-acetylglucosaminidase 819:841 arg1 N-phenylcarbamate 775:791 O-(2-acetamido-2-deoxy-d-glucopyranosylidenamino) N-phenylcarbamate 725:791 O-(2-acetamido-2-deoxy-d-glucopyranosylidenamino) N-phenylcarbamate (PUGNAc) 725:800 Upregulation of O-GlcNAcylation in metabolically active rat brain slices by O-(2-acetamido-2-deoxy-d-glucopyranosylidenamino) N-phenylcarbamate (PUGNAc), an inhibitor of N-acetylglucosaminidase, increased the phosphorylation of tau at the PKA site, Ser214, but not at the non-PKA site, Thr205. 26840030 6 43 theme N-acetylglucosaminidase 819:841 arg1 inhibitor 806:814 an inhibitor 803:814 an inhibitor of N-acetylglucosaminidase 803:841 Upregulation of O-GlcNAcylation in metabolically active rat brain slices by O-(2-acetamido-2-deoxy-d-glucopyranosylidenamino) N-phenylcarbamate (PUGNAc), an inhibitor of N-acetylglucosaminidase, increased the phosphorylation of tau at the PKA site, Ser214, but not at the non-PKA site, Thr205. 26840030 5 44 theme subcellular 573:583 arg1 location 585:592 the subcellular location 569:592 the subcellular location of PKAcα and PKAcβ 569:611 O-GlcNAcylation regulated the subcellular location of PKAcα and PKAcβ and enhanced their kinase activity. 26840030 2 45 theme critical 290:297 arg1 role 299:302 a critical role 288:302 a critical role 288:302 Protein kinase A (PKA)-CREB signaling plays a critical role in learning and memory. 26840030 5 46 theme kinase 632:637 arg1 activity 639:646 their kinase activity 626:646 their kinase activity 626:646 O-GlcNAcylation regulated the subcellular location of PKAcα and PKAcβ and enhanced their kinase activity. 26840030 7 47 theme tau 1080:1082 arg1 decreases 1022:1030 decreases 1022:1030 decreases in the phosphorylation of CREB at Ser133 and of tau 1022:1082 In contrast, in rat and mouse brains, downregulation of O-GlcNAcylation caused decreases in the phosphorylation of CREB at Ser133 and of tau at Ser214, but not at Thr205. 26840030 6 48 theme brain 709:713 arg1 slices 715:720 metabolically active rat brain slices 684:720 metabolically active rat brain slices 684:720 Upregulation of O-GlcNAcylation in metabolically active rat brain slices by O-(2-acetamido-2-deoxy-d-glucopyranosylidenamino) N-phenylcarbamate (PUGNAc), an inhibitor of N-acetylglucosaminidase, increased the phosphorylation of tau at the PKA site, Ser214, but not at the non-PKA site, Thr205. 26840030 9 49 theme PKA-CREB 1481:1488 arg1 signaling 1490:1498 PKA-CREB signaling 1481:1498 PKA-CREB signaling 1481:1498 These results indicate that in addition to cAMP and phosphorylation, O-GlcNAcylation is a novel mechanism that regulates PKA-CREB signaling. 26840030 8 50 from learning 1331:1338 arg1 mice 1354:1357 mice 1354:1357 mice 1354:1357 Reduction in O-GlcNAcylation through intracerebroventricular injection of 6-diazo-5-oxo-l-norleucine (DON), the inhibitor of glutamine fructose-6-phosphate amidotransferase, suppressed PKA-CREB signaling and impaired learning and memory in mice. 26840030 10 51 dep learning 1589:1596 arg1 deficits 1609:1616 deficits 1609:1616 deficits 1609:1616 Downregulation of O-GlcNAcylation suppresses PKA-CREB signaling and consequently causes learning and memory deficits in AD. 26840030 6 52 from Upregulation 649:660 arg1 slices 715:720 metabolically active rat brain slices 684:720 metabolically active rat brain slices 684:720 Upregulation of O-GlcNAcylation in metabolically active rat brain slices by O-(2-acetamido-2-deoxy-d-glucopyranosylidenamino) N-phenylcarbamate (PUGNAc), an inhibitor of N-acetylglucosaminidase, increased the phosphorylation of tau at the PKA site, Ser214, but not at the non-PKA site, Thr205. 26840030 6 53 theme rat 705:707 arg1 slices 715:720 metabolically active rat brain slices 684:720 metabolically active rat brain slices 684:720 Upregulation of O-GlcNAcylation in metabolically active rat brain slices by O-(2-acetamido-2-deoxy-d-glucopyranosylidenamino) N-phenylcarbamate (PUGNAc), an inhibitor of N-acetylglucosaminidase, increased the phosphorylation of tau at the PKA site, Ser214, but not at the non-PKA site, Thr205. 26840030 7 54 theme CREB 1058:1061 arg1 phosphorylation 1039:1053 the phosphorylation 1035:1053 the phosphorylation of CREB at Ser133 1035:1071 In contrast, in rat and mouse brains, downregulation of O-GlcNAcylation caused decreases in the phosphorylation of CREB at Ser133 and of tau at Ser214, but not at Thr205. 26840030 4 55 link O-linked 502:509 arg1 O-GlcNAc 532:539 O-GlcNAc 532:539 O-GlcNAc 532:539 In this study, we found that PKA catalytic subunits (PKAcs) were posttranslationally modified by O-linked N-acetylglucosamine (O-GlcNAc). 26840030 4 55 link O-linked 502:509 arg1 N-acetylglucosamine 511:529 O-linked N-acetylglucosamine 502:529 O-linked N-acetylglucosamine (O-GlcNAc) 502:540 In this study, we found that PKA catalytic subunits (PKAcs) were posttranslationally modified by O-linked N-acetylglucosamine (O-GlcNAc). 26840030 8 56 dep glutamine 1239:1247 arg1 amidotransferase 1270:1285 fructose-6-phosphate amidotransferase 1249:1285 glutamine fructose-6-phosphate amidotransferase 1239:1285 Reduction in O-GlcNAcylation through intracerebroventricular injection of 6-diazo-5-oxo-l-norleucine (DON), the inhibitor of glutamine fructose-6-phosphate amidotransferase, suppressed PKA-CREB signaling and impaired learning and memory in mice. 26840030 0 57 attach linked 90:95 arg1 memory 113:118 memory 113:118 memory 113:118 O-GlcNAcylation of protein kinase A catalytic subunits enhances its activity: a mechanism linked to learning and memory deficits in Alzheimer's disease. 26840030 0 57 attach linked 90:95 arg2 mechanism 80:88 a mechanism 78:88 a mechanism linked to learning and memory deficits in Alzheimer's disease 78:150 O-GlcNAcylation of protein kinase A catalytic subunits enhances its activity: a mechanism linked to learning and memory deficits in Alzheimer's disease. 26840030 0 57 attach linked 90:95 arg1 learning 100:107 learning 100:107 learning 100:107 O-GlcNAcylation of protein kinase A catalytic subunits enhances its activity: a mechanism linked to learning and memory deficits in Alzheimer's disease. 26840030 1 58 theme memory 209:214 arg1 loss 216:219 memory loss 209:219 memory loss 209:219 Alzheimer's disease (AD) is characterized clinically by memory loss and cognitive decline. 26840030 3 59 gly O-GlcNAcylation 364:378 arg1 brain 398:402 AD brain 395:402 AD brain 395:402 It is known that glucose uptake and O-GlcNAcylation are reduced in AD brain. 24150277 0 0 theme labeled 93:99 arg1 antibodies 101:110 site-specifically labeled antibodies 75:110 site-specifically labeled antibodies 75:110 Metabolic exploitation of the sialic acid biosynthetic pathway to generate site-specifically labeled antibodies. 24150277 4 1 theme HB8059 536:541 arg1 hybridoma 543:551 The HB8059 hybridoma 532:551 The HB8059 hybridoma 532:551 The HB8059 hybridoma was cultured with peracetylated N-azidoacetlymannosamine (Ac4ManNAz). 24150277 3 2 from site 483:486 arg1 azido-sugar 463:473 an altered azido-sugar 452:473 an altered azido-sugar at this site 452:486 We sought to develop an antibody with an altered azido-sugar at this site whereby site-specific label could be added. 24150277 13 3 theme conserved 1577:1585 arg1 site 1605:1608 the conserved CH2 glycosylation site 1573:1608 the conserved CH2 glycosylation site 1573:1608 We successfully produced an antibody with an azido-sugar at the conserved CH2 glycosylation site. 24150277 2 4 from utilization 345:355 arg1 domain 406:411 the CH2 domain 398:411 the CH2 domain 398:411 A potential mechanism for site-specific conjugation involves utilization of the conserved N-glycosylation site in the CH2 domain. 24150277 14 5 theme heavy 1774:1778 arg1 chain 1780:1784 the heavy chain 1770:1784 the heavy chain 1770:1784 We were able to utilize this azide to label the antibody with biotin or fluorescent label and demonstrate that the label is added in a site-specific manner to the heavy chain, N-linked glycosylation site. 24150277 14 5 theme heavy 1774:1778 arg1 site 1810:1813 N-linked glycosylation site 1787:1813 N-linked glycosylation site 1787:1813 We were able to utilize this azide to label the antibody with biotin or fluorescent label and demonstrate that the label is added in a site-specific manner to the heavy chain, N-linked glycosylation site. 24150277 11 6 link N-linked 1325:1332 arg1 glycosidase 1334:1344 a N-linked glycosidase 1323:1344 a N-linked glycosidase 1323:1344 Treatment with a N-linked glycosidase extinguished the band. 24150277 14 7 theme site-specific 1746:1758 arg1 manner 1760:1765 a site-specific manner 1744:1765 a site-specific manner 1744:1765 We were able to utilize this azide to label the antibody with biotin or fluorescent label and demonstrate that the label is added in a site-specific manner to the heavy chain, N-linked glycosylation site. 24150277 2 8 theme CH2 402:404 arg1 domain 406:411 the CH2 domain 398:411 the CH2 domain 398:411 A potential mechanism for site-specific conjugation involves utilization of the conserved N-glycosylation site in the CH2 domain. 24150277 3 9 dep site-specific 496:508 arg1 label 510:514 label 510:514 label 510:514 We sought to develop an antibody with an altered azido-sugar at this site whereby site-specific label could be added. 24150277 5 10 theme modified 726:733 arg1 reaction 746:753 a modified Staudinger reaction 724:753 a modified Staudinger reaction 724:753 The resulting azido-sugar antibody was conjugated to phosphine-polyethylene glycol (PEG3)-biotin via a modified Staudinger reaction. 24150277 14 11 gly glycosylation 1796:1808 arg2 chain 1780:1784 the heavy chain 1770:1784 the heavy chain 1770:1784 We were able to utilize this azide to label the antibody with biotin or fluorescent label and demonstrate that the label is added in a site-specific manner to the heavy chain, N-linked glycosylation site. 24150277 14 11 gly glycosylation 1796:1808 arg2 site 1810:1813 N-linked glycosylation site 1787:1813 N-linked glycosylation site 1787:1813 We were able to utilize this azide to label the antibody with biotin or fluorescent label and demonstrate that the label is added in a site-specific manner to the heavy chain, N-linked glycosylation site. 24150277 3 12 with antibody 438:445 arg1 azido-sugar 463:473 an altered azido-sugar 452:473 an altered azido-sugar at this site 452:486 We sought to develop an antibody with an altered azido-sugar at this site whereby site-specific label could be added. 24150277 6 13 theme biotinylated 807:818 arg1 antibody 820:827 the biotinylated antibody 803:827 the biotinylated antibody 803:827 Biochemical and functional characterization of the biotinylated antibody was performed. 24150277 15 14 dep in 1875:1876 arg1 vitro 1878:1882 vitro 1878:1882 vitro 1878:1882 Finally, we demonstrated functionality of our antibody for in vitro and in vivo targeting of pancreatic cancer cells. 24150277 5 15 theme Staudinger 735:744 arg1 reaction 746:753 a modified Staudinger reaction 724:753 a modified Staudinger reaction 724:753 The resulting azido-sugar antibody was conjugated to phosphine-polyethylene glycol (PEG3)-biotin via a modified Staudinger reaction. 24150277 5 16 theme phosphine-polyethylene 676:697 arg1 -biotin 712:718 phosphine-polyethylene glycol (PEG3)-biotin 676:718 phosphine-polyethylene glycol (PEG3)-biotin 676:718 The resulting azido-sugar antibody was conjugated to phosphine-polyethylene glycol (PEG3)-biotin via a modified Staudinger reaction. 24150277 1 17 theme conjugation 147:157 arg1 methodology 159:169 a universal site-specific conjugation methodology 121:169 a universal site-specific conjugation methodology for antibodies 121:184 Lack of a universal site-specific conjugation methodology for antibodies limits their potential to be developed as tumor-specific imaging agents or targeted therapeutics. 24150277 13 18 theme glycosylation 1591:1603 arg1 site 1605:1608 the conserved CH2 glycosylation site 1573:1608 the conserved CH2 glycosylation site 1573:1608 We successfully produced an antibody with an azido-sugar at the conserved CH2 glycosylation site. 24150277 5 19 theme glycol 699:704 arg1 -biotin 712:718 phosphine-polyethylene glycol (PEG3)-biotin 676:718 phosphine-polyethylene glycol (PEG3)-biotin 676:718 The resulting azido-sugar antibody was conjugated to phosphine-polyethylene glycol (PEG3)-biotin via a modified Staudinger reaction. 24150277 2 20 theme site-specific 310:322 arg1 conjugation 324:334 site-specific conjugation 310:334 site-specific conjugation 310:334 A potential mechanism for site-specific conjugation involves utilization of the conserved N-glycosylation site in the CH2 domain. 24150277 15 21 theme in 1875:1876 arg1 targeting 1896:1904 in vitro and in vivo targeting 1875:1904 in vitro and in vivo targeting of pancreatic cancer cells 1875:1931 Finally, we demonstrated functionality of our antibody for in vitro and in vivo targeting of pancreatic cancer cells. 24150277 13 22 gly glycosylation 1591:1603 arg2 site 1605:1608 the conserved CH2 glycosylation site 1573:1608 the conserved CH2 glycosylation site 1573:1608 We successfully produced an antibody with an azido-sugar at the conserved CH2 glycosylation site. 24150277 10 23 theme gel 1229:1231 arg1 electrophoresis 1233:1247 sodium dodecyl sulfate-polyacrylamide gel electrophoresis 1191:1247 sodium dodecyl sulfate-polyacrylamide gel electrophoresis 1191:1247 The biotinylated antibody demonstrated a 50 kDa heavy and 25 kDa light chain on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, but demonstrated a single band at 50 kDa on western blot. 24150277 5 24 theme PEG3 707:710 arg1 -biotin 712:718 phosphine-polyethylene glycol (PEG3)-biotin 676:718 phosphine-polyethylene glycol (PEG3)-biotin 676:718 The resulting azido-sugar antibody was conjugated to phosphine-polyethylene glycol (PEG3)-biotin via a modified Staudinger reaction. 24150277 5 25 theme resulting 627:635 arg1 antibody 649:656 The resulting azido-sugar antibody 623:656 The resulting azido-sugar antibody 623:656 The resulting azido-sugar antibody was conjugated to phosphine-polyethylene glycol (PEG3)-biotin via a modified Staudinger reaction. 24150277 9 26 theme μM 1097:1098 arg1 Ac4ManNAz 1100:1108 100 μM Ac4ManNAz 1093:1108 100 μM Ac4ManNAz 1093:1108 The antibody was successfully produced in 100 μM Ac4ManNAz. 24150277 15 27 theme cancer 1920:1925 arg1 cells 1927:1931 pancreatic cancer cells 1909:1931 pancreatic cancer cells 1909:1931 Finally, we demonstrated functionality of our antibody for in vitro and in vivo targeting of pancreatic cancer cells. 24150277 12 28 theme cells 1441:1445 arg1 binding 1414:1420 antigen-specific binding 1397:1420 antigen-specific binding of CA19-9-positive cells 1397:1445 Flow cytometry demonstrated antigen-specific binding of CA19-9-positive cells and the antibody localized to the antigen-positive tumor in vivo. 24150277 9 29 theme 100 1093:1095 arg1 μM 1097:1098 μM 1097:1098 μM 1097:1098 The antibody was successfully produced in 100 μM Ac4ManNAz. 24150277 10 30 theme sulfate-polyacrylamide 1206:1227 arg1 electrophoresis 1233:1247 sodium dodecyl sulfate-polyacrylamide gel electrophoresis 1191:1247 sodium dodecyl sulfate-polyacrylamide gel electrophoresis 1191:1247 The biotinylated antibody demonstrated a 50 kDa heavy and 25 kDa light chain on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, but demonstrated a single band at 50 kDa on western blot. 24150277 10 31 from kDa 1287:1289 arg1 band 1276:1279 a single band 1267:1279 a single band at 50 kDa 1267:1289 The biotinylated antibody demonstrated a 50 kDa heavy and 25 kDa light chain on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, but demonstrated a single band at 50 kDa on western blot. 24150277 5 32 theme azido-sugar 637:647 arg1 antibody 649:656 The resulting azido-sugar antibody 623:656 The resulting azido-sugar antibody 623:656 The resulting azido-sugar antibody was conjugated to phosphine-polyethylene glycol (PEG3)-biotin via a modified Staudinger reaction. 24150277 2 33 theme conserved 364:372 arg1 site 390:393 the conserved N-glycosylation site 360:393 the conserved N-glycosylation site 360:393 A potential mechanism for site-specific conjugation involves utilization of the conserved N-glycosylation site in the CH2 domain. 24150277 6 34 theme functional 772:781 arg1 characterization 783:798 Biochemical and functional characterization 756:798 Biochemical and functional characterization of the biotinylated antibody 756:827 Biochemical and functional characterization of the biotinylated antibody was performed. 24150277 0 35 theme Metabolic 0:8 arg1 exploitation 10:21 Metabolic exploitation 0:21 Metabolic exploitation of the sialic acid biosynthetic pathway 0:61 Metabolic exploitation of the sialic acid biosynthetic pathway to generate site-specifically labeled antibodies. 24150277 10 36 theme single 1269:1274 arg1 band 1276:1279 a single band 1267:1279 a single band at 50 kDa 1267:1289 The biotinylated antibody demonstrated a 50 kDa heavy and 25 kDa light chain on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, but demonstrated a single band at 50 kDa on western blot. 24150277 11 37 theme N-linked 1325:1332 arg1 glycosidase 1334:1344 a N-linked glycosidase 1323:1344 a N-linked glycosidase 1323:1344 Treatment with a N-linked glycosidase extinguished the band. 24150277 7 38 theme pancreatic 946:955 arg1 xenografts 964:973 pancreatic cancer xenografts 946:973 pancreatic cancer xenografts 946:973 The azido-sugar antibody was also labeled with DyLight-650-Phosphine and injected into mice harboring pancreatic cancer xenografts. 24150277 15 39 theme pancreatic 1909:1918 arg1 cells 1927:1931 pancreatic cancer cells 1909:1931 pancreatic cancer cells 1909:1931 Finally, we demonstrated functionality of our antibody for in vitro and in vivo targeting of pancreatic cancer cells. 24150277 12 40 theme antigen-positive 1481:1496 arg1 tumor 1498:1502 the antigen-positive tumor 1477:1502 the antigen-positive tumor 1477:1502 Flow cytometry demonstrated antigen-specific binding of CA19-9-positive cells and the antibody localized to the antigen-positive tumor in vivo. 24150277 13 41 from site 1605:1608 arg1 azido-sugar 1558:1568 an azido-sugar 1555:1568 an azido-sugar at the conserved CH2 glycosylation site 1555:1608 We successfully produced an antibody with an azido-sugar at the conserved CH2 glycosylation site. 24150277 6 42 theme Biochemical 756:766 arg1 characterization 783:798 Biochemical and functional characterization 756:798 Biochemical and functional characterization of the biotinylated antibody 756:827 Biochemical and functional characterization of the biotinylated antibody was performed. 24150277 14 43 link N-linked 1787:1794 arg1 chain 1780:1784 the heavy chain 1770:1784 the heavy chain 1770:1784 We were able to utilize this azide to label the antibody with biotin or fluorescent label and demonstrate that the label is added in a site-specific manner to the heavy chain, N-linked glycosylation site. 24150277 14 43 link N-linked 1787:1794 arg1 site 1810:1813 N-linked glycosylation site 1787:1813 N-linked glycosylation site 1787:1813 We were able to utilize this azide to label the antibody with biotin or fluorescent label and demonstrate that the label is added in a site-specific manner to the heavy chain, N-linked glycosylation site. 24150277 13 44 theme CH2 1587:1589 arg1 site 1605:1608 the conserved CH2 glycosylation site 1573:1608 the conserved CH2 glycosylation site 1573:1608 We successfully produced an antibody with an azido-sugar at the conserved CH2 glycosylation site. 24150277 8 45 theme fluorescent 1031:1041 arg1 camera 1043:1048 an IVIS fluorescent camera 1023:1048 an IVIS fluorescent camera 1023:1048 The tumors were dissected and imaged utilizing an IVIS fluorescent camera. 24150277 12 46 theme antigen-specific 1397:1412 arg1 binding 1414:1420 antigen-specific binding 1397:1420 antigen-specific binding of CA19-9-positive cells 1397:1445 Flow cytometry demonstrated antigen-specific binding of CA19-9-positive cells and the antibody localized to the antigen-positive tumor in vivo. 24150277 0 47 theme acid 37:40 arg1 pathway 55:61 the sialic acid biosynthetic pathway 26:61 the sialic acid biosynthetic pathway 26:61 Metabolic exploitation of the sialic acid biosynthetic pathway to generate site-specifically labeled antibodies. 24150277 10 48 theme kDa 1155:1157 arg1 heavy 1159:1163 a 50 kDa heavy 1150:1163 a 50 kDa heavy 1150:1163 The biotinylated antibody demonstrated a 50 kDa heavy and 25 kDa light chain on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, but demonstrated a single band at 50 kDa on western blot. 24150277 8 49 theme IVIS 1026:1029 arg1 camera 1043:1048 an IVIS fluorescent camera 1023:1048 an IVIS fluorescent camera 1023:1048 The tumors were dissected and imaged utilizing an IVIS fluorescent camera. 24150277 1 50 theme tumor-specific 228:241 arg1 agents 251:256 tumor-specific imaging agents 228:256 tumor-specific imaging agents 228:256 Lack of a universal site-specific conjugation methodology for antibodies limits their potential to be developed as tumor-specific imaging agents or targeted therapeutics. 24150277 0 51 theme sialic 30:35 arg1 pathway 55:61 the sialic acid biosynthetic pathway 26:61 the sialic acid biosynthetic pathway 26:61 Metabolic exploitation of the sialic acid biosynthetic pathway to generate site-specifically labeled antibodies. 24150277 4 52 theme peracetylated 571:583 arg1 N-azidoacetlymannosamine 585:608 peracetylated N-azidoacetlymannosamine 571:608 peracetylated N-azidoacetlymannosamine (Ac4ManNAz) 571:620 The HB8059 hybridoma was cultured with peracetylated N-azidoacetlymannosamine (Ac4ManNAz). 24150277 4 52 theme peracetylated 571:583 arg1 Ac4ManNAz 611:619 Ac4ManNAz 611:619 Ac4ManNAz 611:619 The HB8059 hybridoma was cultured with peracetylated N-azidoacetlymannosamine (Ac4ManNAz). 24150277 3 53 theme altered 455:461 arg1 azido-sugar 463:473 an altered azido-sugar 452:473 an altered azido-sugar at this site 452:486 We sought to develop an antibody with an altered azido-sugar at this site whereby site-specific label could be added. 24150277 10 54 theme 50 1152:1153 arg1 kDa 1155:1157 kDa 1155:1157 kDa 1155:1157 The biotinylated antibody demonstrated a 50 kDa heavy and 25 kDa light chain on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, but demonstrated a single band at 50 kDa on western blot. 24150277 10 55 theme western 1294:1300 arg1 blot 1302:1305 western blot 1294:1305 western blot 1294:1305 The biotinylated antibody demonstrated a 50 kDa heavy and 25 kDa light chain on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, but demonstrated a single band at 50 kDa on western blot. 24150277 1 56 theme imaging 243:249 arg1 agents 251:256 tumor-specific imaging agents 228:256 tumor-specific imaging agents 228:256 Lack of a universal site-specific conjugation methodology for antibodies limits their potential to be developed as tumor-specific imaging agents or targeted therapeutics. 24150277 0 57 theme pathway 55:61 arg1 exploitation 10:21 Metabolic exploitation 0:21 Metabolic exploitation of the sialic acid biosynthetic pathway 0:61 Metabolic exploitation of the sialic acid biosynthetic pathway to generate site-specifically labeled antibodies. 24150277 7 58 theme cancer 957:962 arg1 xenografts 964:973 pancreatic cancer xenografts 946:973 pancreatic cancer xenografts 946:973 The azido-sugar antibody was also labeled with DyLight-650-Phosphine and injected into mice harboring pancreatic cancer xenografts. 24150277 12 59 theme Flow 1369:1372 arg1 cytometry 1374:1382 Flow cytometry 1369:1382 Flow cytometry 1369:1382 Flow cytometry demonstrated antigen-specific binding of CA19-9-positive cells and the antibody localized to the antigen-positive tumor in vivo. 24150277 0 60 theme biosynthetic 42:53 arg1 pathway 55:61 the sialic acid biosynthetic pathway 26:61 the sialic acid biosynthetic pathway 26:61 Metabolic exploitation of the sialic acid biosynthetic pathway to generate site-specifically labeled antibodies. 24150277 10 61 theme light 1176:1180 arg1 chain 1182:1186 25 kDa light chain 1169:1186 25 kDa light chain 1169:1186 The biotinylated antibody demonstrated a 50 kDa heavy and 25 kDa light chain on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, but demonstrated a single band at 50 kDa on western blot. 24150277 1 62 theme universal 123:131 arg1 methodology 159:169 a universal site-specific conjugation methodology 121:169 a universal site-specific conjugation methodology for antibodies 121:184 Lack of a universal site-specific conjugation methodology for antibodies limits their potential to be developed as tumor-specific imaging agents or targeted therapeutics. 24150277 15 63 dep in 1888:1889 arg1 vivo 1891:1894 vivo 1891:1894 vivo 1891:1894 Finally, we demonstrated functionality of our antibody for in vitro and in vivo targeting of pancreatic cancer cells. 24150277 2 64 gly N-glycosylation 374:388 arg2 site 390:393 the conserved N-glycosylation site 360:393 the conserved N-glycosylation site 360:393 A potential mechanism for site-specific conjugation involves utilization of the conserved N-glycosylation site in the CH2 domain. 24150277 10 65 theme kDa 1172:1174 arg1 chain 1182:1186 25 kDa light chain 1169:1186 25 kDa light chain 1169:1186 The biotinylated antibody demonstrated a 50 kDa heavy and 25 kDa light chain on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, but demonstrated a single band at 50 kDa on western blot. 24150277 14 66 dep the 1722:1724 arg1 label 1726:1730 label 1726:1730 label 1726:1730 We were able to utilize this azide to label the antibody with biotin or fluorescent label and demonstrate that the label is added in a site-specific manner to the heavy chain, N-linked glycosylation site. 24150277 1 67 theme site-specific 133:145 arg1 methodology 159:169 a universal site-specific conjugation methodology 121:169 a universal site-specific conjugation methodology for antibodies 121:184 Lack of a universal site-specific conjugation methodology for antibodies limits their potential to be developed as tumor-specific imaging agents or targeted therapeutics. 24150277 15 68 theme in 1888:1889 arg1 targeting 1896:1904 in vitro and in vivo targeting 1875:1904 in vitro and in vivo targeting of pancreatic cancer cells 1875:1931 Finally, we demonstrated functionality of our antibody for in vitro and in vivo targeting of pancreatic cancer cells. 24150277 7 69 theme azido-sugar 848:858 arg1 antibody 860:867 The azido-sugar antibody 844:867 The azido-sugar antibody 844:867 The azido-sugar antibody was also labeled with DyLight-650-Phosphine and injected into mice harboring pancreatic cancer xenografts. 24150277 10 70 theme 25 1169:1170 arg1 kDa 1172:1174 kDa 1172:1174 kDa 1172:1174 The biotinylated antibody demonstrated a 50 kDa heavy and 25 kDa light chain on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, but demonstrated a single band at 50 kDa on western blot. 24150277 2 71 theme potential 286:294 arg1 mechanism 296:304 A potential mechanism 284:304 A potential mechanism for site-specific conjugation 284:334 A potential mechanism for site-specific conjugation involves utilization of the conserved N-glycosylation site in the CH2 domain. 24150277 2 72 theme N-glycosylation 374:388 arg1 site 390:393 the conserved N-glycosylation site 360:393 the conserved N-glycosylation site 360:393 A potential mechanism for site-specific conjugation involves utilization of the conserved N-glycosylation site in the CH2 domain. 24150277 15 73 theme cells 1927:1931 arg1 targeting 1896:1904 in vitro and in vivo targeting 1875:1904 in vitro and in vivo targeting of pancreatic cancer cells 1875:1931 Finally, we demonstrated functionality of our antibody for in vitro and in vivo targeting of pancreatic cancer cells. 24150277 2 74 theme site 390:393 arg1 utilization 345:355 utilization 345:355 utilization of the conserved N-glycosylation site in the CH2 domain 345:411 A potential mechanism for site-specific conjugation involves utilization of the conserved N-glycosylation site in the CH2 domain. 24150277 12 75 theme CA19-9-positive 1425:1439 arg1 cells 1441:1445 CA19-9-positive cells 1425:1445 CA19-9-positive cells 1425:1445 Flow cytometry demonstrated antigen-specific binding of CA19-9-positive cells and the antibody localized to the antigen-positive tumor in vivo. 24150277 14 76 theme glycosylation 1796:1808 arg1 chain 1780:1784 the heavy chain 1770:1784 the heavy chain 1770:1784 We were able to utilize this azide to label the antibody with biotin or fluorescent label and demonstrate that the label is added in a site-specific manner to the heavy chain, N-linked glycosylation site. 24150277 14 76 theme glycosylation 1796:1808 arg1 site 1810:1813 N-linked glycosylation site 1787:1813 N-linked glycosylation site 1787:1813 We were able to utilize this azide to label the antibody with biotin or fluorescent label and demonstrate that the label is added in a site-specific manner to the heavy chain, N-linked glycosylation site. 24150277 10 77 theme biotinylated 1115:1126 arg1 antibody 1128:1135 The biotinylated antibody 1111:1135 The biotinylated antibody 1111:1135 The biotinylated antibody demonstrated a 50 kDa heavy and 25 kDa light chain on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, but demonstrated a single band at 50 kDa on western blot. 24150277 1 78 theme methodology 159:169 arg1 Lack 113:116 Lack 113:116 Lack of a universal site-specific conjugation methodology for antibodies 113:184 Lack of a universal site-specific conjugation methodology for antibodies limits their potential to be developed as tumor-specific imaging agents or targeted therapeutics. 24150277 1 79 theme targeted 261:268 arg1 therapeutics 270:281 targeted therapeutics 261:281 targeted therapeutics 261:281 Lack of a universal site-specific conjugation methodology for antibodies limits their potential to be developed as tumor-specific imaging agents or targeted therapeutics. 24150277 14 80 theme N-linked 1787:1794 arg1 chain 1780:1784 the heavy chain 1770:1784 the heavy chain 1770:1784 We were able to utilize this azide to label the antibody with biotin or fluorescent label and demonstrate that the label is added in a site-specific manner to the heavy chain, N-linked glycosylation site. 24150277 14 80 theme N-linked 1787:1794 arg1 site 1810:1813 N-linked glycosylation site 1787:1813 N-linked glycosylation site 1787:1813 We were able to utilize this azide to label the antibody with biotin or fluorescent label and demonstrate that the label is added in a site-specific manner to the heavy chain, N-linked glycosylation site. 24150277 6 81 theme antibody 820:827 arg1 characterization 783:798 Biochemical and functional characterization 756:798 Biochemical and functional characterization of the biotinylated antibody 756:827 Biochemical and functional characterization of the biotinylated antibody was performed. 24150277 11 82 with Treatment 1308:1316 arg1 glycosidase 1334:1344 a N-linked glycosidase 1323:1344 a N-linked glycosidase 1323:1344 Treatment with a N-linked glycosidase extinguished the band. 24150277 15 83 theme antibody 1862:1869 arg1 functionality 1841:1853 functionality 1841:1853 functionality of our antibody for in vitro and in vivo targeting of pancreatic cancer cells 1841:1931 Finally, we demonstrated functionality of our antibody for in vitro and in vivo targeting of pancreatic cancer cells. 25945896 12 0 theme specific 2207:2214 arg1 glycosites 2216:2225 specific glycosites 2207:2225 specific glycosites that might be missing from the predetermined glycan databases 2207:2287 Additionally, spectral library matching gives the user the possibility of identifying novel or modified glycans on specific glycosites that might be missing from the predetermined glycan databases. 25945896 10 1 from peptides 1733:1740 arg1 enrichment 1685:1694 enrichment 1685:1694 enrichment of glycopeptides from global tryptic peptides 1685:1740 Without enrichment of glycopeptides from global tryptic peptides and at a false discovery rate of 1%, 1008 glycan-containing MS/MS spectra were assigned to 769 unique intact N-linked glycopeptides, representing 344 N-linked glycosites with 57 different N-glycans. 25945896 10 1 from peptides 1733:1740 arg1 glycopeptides 1699:1711 glycopeptides 1699:1711 glycopeptides from global tryptic peptides 1699:1740 Without enrichment of glycopeptides from global tryptic peptides and at a false discovery rate of 1%, 1008 glycan-containing MS/MS spectra were assigned to 769 unique intact N-linked glycopeptides, representing 344 N-linked glycosites with 57 different N-glycans. 25945896 7 2 theme spectral 1215:1222 arg1 library 1224:1230 the spectral library 1211:1230 the spectral library generated from glycosite-containing peptides 1211:1275 These oxonium-ion-containing spectra were then compared with the spectral library generated from glycosite-containing peptides, resulting in assignment of each intact glycopeptide MS/MS spectrum to a specific glycosite-containing peptide. 25945896 11 3 theme intact 2027:2032 arg1 glycopeptides 2034:2046 intact glycopeptides 2027:2046 intact glycopeptides 2027:2046 Spectral library matching using GPQuest assigns the HCD LC-MS/MS generated spectra of intact glycopeptides in an automated and high-throughput manner. 25945896 1 4 theme Glycoprotein 126:137 arg1 changes 139:145 Glycoprotein changes 126:145 Glycoprotein changes 126:145 Glycoprotein changes occur in not only protein abundance but also the occupancy of each glycosylation site by different glycoforms during biological or pathological processes. 25945896 10 5 theme global 1718:1723 arg1 peptides 1733:1740 global tryptic peptides 1718:1740 global tryptic peptides 1718:1740 Without enrichment of glycopeptides from global tryptic peptides and at a false discovery rate of 1%, 1008 glycan-containing MS/MS spectra were assigned to 769 unique intact N-linked glycopeptides, representing 344 N-linked glycosites with 57 different N-glycans. 25945896 10 6 link N-linked 1851:1858 arg1 glycopeptides 1860:1872 769 unique intact N-linked glycopeptides 1833:1872 769 unique intact N-linked glycopeptides 1833:1872 Without enrichment of glycopeptides from global tryptic peptides and at a false discovery rate of 1%, 1008 glycan-containing MS/MS spectra were assigned to 769 unique intact N-linked glycopeptides, representing 344 N-linked glycosites with 57 different N-glycans. 25945896 10 7 theme N-linked 1892:1899 arg1 glycosites 1901:1910 344 N-linked glycosites 1888:1910 344 N-linked glycosites with 57 different N-glycans 1888:1938 Without enrichment of glycopeptides from global tryptic peptides and at a false discovery rate of 1%, 1008 glycan-containing MS/MS spectra were assigned to 769 unique intact N-linked glycopeptides, representing 344 N-linked glycosites with 57 different N-glycans. 25945896 10 8 theme glycopeptides 1699:1711 arg1 enrichment 1685:1694 enrichment 1685:1694 enrichment of glycopeptides from global tryptic peptides 1685:1740 Without enrichment of glycopeptides from global tryptic peptides and at a false discovery rate of 1%, 1008 glycan-containing MS/MS spectra were assigned to 769 unique intact N-linked glycopeptides, representing 344 N-linked glycosites with 57 different N-glycans. 25945896 5 9 theme peptides 922:929 arg1 library 890:896 a spectral library 879:896 a spectral library of glycosite-containing peptides in the sample 879:943 In this algorithm, a spectral library of glycosite-containing peptides in the sample was built by analyzing the isolated glycosite-containing peptides using HCD LC-MS/MS. 25945896 10 10 theme different 1920:1928 arg1 N-glycans 1930:1938 57 different N-glycans 1917:1938 57 different N-glycans 1917:1938 Without enrichment of glycopeptides from global tryptic peptides and at a false discovery rate of 1%, 1008 glycan-containing MS/MS spectra were assigned to 769 unique intact N-linked glycopeptides, representing 344 N-linked glycosites with 57 different N-glycans. 25945896 2 11 theme mass 321:324 arg1 spectrometry 326:337 mass spectrometry 321:337 mass spectrometry instrumentation 321:353 Recent advances in mass spectrometry instrumentation and techniques have facilitated analysis of intact glycopeptides in complex biological samples by allowing the users to generate spectra of intact glycopeptides with glycans attached to each specific glycosylation site. 25945896 3 12 gly glycopeptides 642:654 arg2 glycopeptides 642:654 the glycopeptides 638:654 the glycopeptides 638:654 However, assigning these spectra, leading to identification of the glycopeptides, is challenging. 25945896 9 13 theme extracts 1635:1642 arg1 spectra 1616:1622 LC-MS/MS spectra 1607:1622 LC-MS/MS spectra of protein extracts from prostate tumor LNCaP cells 1607:1674 Using GPQuest, we analyzed LC-MS/MS spectra of protein extracts from prostate tumor LNCaP cells. 25945896 5 14 theme spectral 881:888 arg1 library 890:896 a spectral library 879:896 a spectral library of glycosite-containing peptides in the sample 879:943 In this algorithm, a spectral library of glycosite-containing peptides in the sample was built by analyzing the isolated glycosite-containing peptides using HCD LC-MS/MS. 25945896 11 15 gly glycopeptides 2034:2046 arg2 glycopeptides 2034:2046 intact glycopeptides 2027:2046 intact glycopeptides 2027:2046 Spectral library matching using GPQuest assigns the HCD LC-MS/MS generated spectra of intact glycopeptides in an automated and high-throughput manner. 25945896 11 16 theme automated 2054:2062 arg1 manner 2084:2089 an automated and high-throughput manner 2051:2089 an automated and high-throughput manner 2051:2089 Spectral library matching using GPQuest assigns the HCD LC-MS/MS generated spectra of intact glycopeptides in an automated and high-throughput manner. 25945896 4 17 gly glycopeptides 761:773 arg2 glycopeptides 761:773 intact glycopeptides 754:773 intact glycopeptides using higher-energy collisional dissociation (HCD) fragmentation of complex samples 754:857 Here, we report an algorithm, named GPQuest, for site-specific identification of intact glycopeptides using higher-energy collisional dissociation (HCD) fragmentation of complex samples. 25945896 3 18 theme glycopeptides 642:654 arg1 identification 620:633 identification 620:633 identification of the glycopeptides 620:654 However, assigning these spectra, leading to identification of the glycopeptides, is challenging. 25945896 5 19 from library 890:896 arg1 sample 938:943 the sample 934:943 the sample 934:943 In this algorithm, a spectral library of glycosite-containing peptides in the sample was built by analyzing the isolated glycosite-containing peptides using HCD LC-MS/MS. 25945896 10 20 theme false 1751:1755 arg1 rate 1767:1770 a false discovery rate 1749:1770 a false discovery rate of 1% 1749:1776 Without enrichment of glycopeptides from global tryptic peptides and at a false discovery rate of 1%, 1008 glycan-containing MS/MS spectra were assigned to 769 unique intact N-linked glycopeptides, representing 344 N-linked glycosites with 57 different N-glycans. 25945896 9 21 theme protein 1627:1633 arg1 extracts 1635:1642 protein extracts 1627:1642 protein extracts 1627:1642 Using GPQuest, we analyzed LC-MS/MS spectra of protein extracts from prostate tumor LNCaP cells. 25945896 9 22 from cells 1670:1674 arg1 spectra 1616:1622 LC-MS/MS spectra 1607:1622 LC-MS/MS spectra of protein extracts from prostate tumor LNCaP cells 1607:1674 Using GPQuest, we analyzed LC-MS/MS spectra of protein extracts from prostate tumor LNCaP cells. 25945896 4 23 theme glycopeptides 761:773 arg1 identification 736:749 site-specific identification 722:749 site-specific identification of intact glycopeptides using higher-energy collisional dissociation (HCD) fragmentation of complex samples 722:857 Here, we report an algorithm, named GPQuest, for site-specific identification of intact glycopeptides using higher-energy collisional dissociation (HCD) fragmentation of complex samples. 25945896 8 24 theme glycopeptide 1508:1519 arg1 peptide 1550:1556 the glycosite-containing peptide 1525:1556 the glycosite-containing peptide to a glycan database 1525:1577 The glycan occupying each glycosite was determined by matching the mass difference between the precursor ion of intact glycopeptide and the glycosite-containing peptide to a glycan database. 25945896 8 24 theme glycopeptide 1508:1519 arg1 ion 1494:1496 the precursor ion 1480:1496 the precursor ion of intact glycopeptide 1480:1519 The glycan occupying each glycosite was determined by matching the mass difference between the precursor ion of intact glycopeptide and the glycosite-containing peptide to a glycan database. 25945896 4 25 theme collisional 795:805 arg1 fragmentation 826:838 higher-energy collisional dissociation (HCD) fragmentation 781:838 higher-energy collisional dissociation (HCD) fragmentation of complex samples 781:857 Here, we report an algorithm, named GPQuest, for site-specific identification of intact glycopeptides using higher-energy collisional dissociation (HCD) fragmentation of complex samples. 25945896 5 26 theme glycosite-containing 981:1000 arg1 peptides 1002:1009 the isolated glycosite-containing peptides 968:1009 the isolated glycosite-containing peptides using HCD LC-MS/MS 968:1028 In this algorithm, a spectral library of glycosite-containing peptides in the sample was built by analyzing the isolated glycosite-containing peptides using HCD LC-MS/MS. 25945896 6 27 theme oxonium 1093:1099 arg1 ions 1119:1122 signature ions 1109:1122 signature ions for glycopeptide spectra 1109:1147 Spectra of intact glycopeptides were selected by using glycan oxonium ions as signature ions for glycopeptide spectra. 25945896 6 27 theme oxonium 1093:1099 arg1 ions 1101:1104 glycan oxonium ions 1086:1104 glycan oxonium ions 1086:1104 Spectra of intact glycopeptides were selected by using glycan oxonium ions as signature ions for glycopeptide spectra. 25945896 0 28 theme Site-Specific 51:63 arg1 Assignment 65:74 Site-Specific Assignment 51:74 Site-Specific Assignment of Tandem Mass Spectra to Intact N-glycopeptides 51:123 GPQuest: A Spectral Library Matching Algorithm for Site-Specific Assignment of Tandem Mass Spectra to Intact N-glycopeptides. 25945896 10 29 gly glycopeptides 1860:1872 arg2 glycopeptides 1860:1872 769 unique intact N-linked glycopeptides 1833:1872 769 unique intact N-linked glycopeptides 1833:1872 Without enrichment of glycopeptides from global tryptic peptides and at a false discovery rate of 1%, 1008 glycan-containing MS/MS spectra were assigned to 769 unique intact N-linked glycopeptides, representing 344 N-linked glycosites with 57 different N-glycans. 25945896 9 30 theme tumor 1658:1662 arg1 cells 1670:1674 prostate tumor LNCaP cells 1649:1674 prostate tumor LNCaP cells 1649:1674 Using GPQuest, we analyzed LC-MS/MS spectra of protein extracts from prostate tumor LNCaP cells. 25945896 4 31 theme site-specific 722:734 arg1 identification 736:749 site-specific identification 722:749 site-specific identification of intact glycopeptides using higher-energy collisional dissociation (HCD) fragmentation of complex samples 722:857 Here, we report an algorithm, named GPQuest, for site-specific identification of intact glycopeptides using higher-energy collisional dissociation (HCD) fragmentation of complex samples. 25945896 7 32 theme MS/MS 1330:1334 arg1 spectrum 1336:1343 each intact glycopeptide MS/MS spectrum 1305:1343 each intact glycopeptide MS/MS spectrum 1305:1343 These oxonium-ion-containing spectra were then compared with the spectral library generated from glycosite-containing peptides, resulting in assignment of each intact glycopeptide MS/MS spectrum to a specific glycosite-containing peptide. 25945896 4 33 theme HCD 821:823 arg1 fragmentation 826:838 higher-energy collisional dissociation (HCD) fragmentation 781:838 higher-energy collisional dissociation (HCD) fragmentation of complex samples 781:857 Here, we report an algorithm, named GPQuest, for site-specific identification of intact glycopeptides using higher-energy collisional dissociation (HCD) fragmentation of complex samples. 25945896 7 34 gly glycopeptide 1317:1328 arg2 glycopeptide 1317:1328 each intact glycopeptide MS/MS spectrum 1305:1343 each intact glycopeptide MS/MS spectrum 1305:1343 These oxonium-ion-containing spectra were then compared with the spectral library generated from glycosite-containing peptides, resulting in assignment of each intact glycopeptide MS/MS spectrum to a specific glycosite-containing peptide. 25945896 0 35 theme Mass 86:89 arg1 Spectra 91:97 Tandem Mass Spectra 79:97 Tandem Mass Spectra 79:97 GPQuest: A Spectral Library Matching Algorithm for Site-Specific Assignment of Tandem Mass Spectra to Intact N-glycopeptides. 25945896 12 36 gly glycosites 2216:2225 arg2 glycosites 2216:2225 specific glycosites 2207:2225 specific glycosites that might be missing from the predetermined glycan databases 2207:2287 Additionally, spectral library matching gives the user the possibility of identifying novel or modified glycans on specific glycosites that might be missing from the predetermined glycan databases. 25945896 5 37 from sample 938:943 arg1 library 890:896 a spectral library 879:896 a spectral library of glycosite-containing peptides in the sample 879:943 In this algorithm, a spectral library of glycosite-containing peptides in the sample was built by analyzing the isolated glycosite-containing peptides using HCD LC-MS/MS. 25945896 6 38 theme glycopeptides 1049:1061 arg1 Spectra 1031:1037 Spectra 1031:1037 Spectra of intact glycopeptides 1031:1061 Spectra of intact glycopeptides were selected by using glycan oxonium ions as signature ions for glycopeptide spectra. 25945896 2 39 theme glycosylation 555:567 arg1 site 569:572 each specific glycosylation site 541:572 each specific glycosylation site 541:572 Recent advances in mass spectrometry instrumentation and techniques have facilitated analysis of intact glycopeptides in complex biological samples by allowing the users to generate spectra of intact glycopeptides with glycans attached to each specific glycosylation site. 25945896 8 40 theme precursor 1484:1492 arg1 ion 1494:1496 the precursor ion 1480:1496 the precursor ion of intact glycopeptide 1480:1519 The glycan occupying each glycosite was determined by matching the mass difference between the precursor ion of intact glycopeptide and the glycosite-containing peptide to a glycan database. 25945896 2 41 theme biological 431:440 arg1 samples 442:448 complex biological samples 423:448 complex biological samples 423:448 Recent advances in mass spectrometry instrumentation and techniques have facilitated analysis of intact glycopeptides in complex biological samples by allowing the users to generate spectra of intact glycopeptides with glycans attached to each specific glycosylation site. 25945896 2 42 gly glycosylation 555:567 arg2 site 569:572 each specific glycosylation site 541:572 each specific glycosylation site 541:572 Recent advances in mass spectrometry instrumentation and techniques have facilitated analysis of intact glycopeptides in complex biological samples by allowing the users to generate spectra of intact glycopeptides with glycans attached to each specific glycosylation site. 25945896 2 43 gly glycopeptides 406:418 arg2 glycopeptides 406:418 intact glycopeptides 399:418 intact glycopeptides in complex biological samples 399:448 Recent advances in mass spectrometry instrumentation and techniques have facilitated analysis of intact glycopeptides in complex biological samples by allowing the users to generate spectra of intact glycopeptides with glycans attached to each specific glycosylation site. 25945896 4 44 theme higher-energy 781:793 arg1 fragmentation 826:838 higher-energy collisional dissociation (HCD) fragmentation 781:838 higher-energy collisional dissociation (HCD) fragmentation of complex samples 781:857 Here, we report an algorithm, named GPQuest, for site-specific identification of intact glycopeptides using higher-energy collisional dissociation (HCD) fragmentation of complex samples. 25945896 10 45 theme % 1776:1776 arg1 rate 1767:1770 a false discovery rate 1749:1770 a false discovery rate of 1% 1749:1776 Without enrichment of glycopeptides from global tryptic peptides and at a false discovery rate of 1%, 1008 glycan-containing MS/MS spectra were assigned to 769 unique intact N-linked glycopeptides, representing 344 N-linked glycosites with 57 different N-glycans. 25945896 1 46 theme pathological 278:289 arg1 processes 291:299 biological or pathological processes 264:299 biological or pathological processes 264:299 Glycoprotein changes occur in not only protein abundance but also the occupancy of each glycosylation site by different glycoforms during biological or pathological processes. 25945896 12 47 from databases 2279:2287 arg1 missing 2241:2247 missing 2241:2247 missing 2241:2247 Additionally, spectral library matching gives the user the possibility of identifying novel or modified glycans on specific glycosites that might be missing from the predetermined glycan databases. 25945896 6 48 theme glycopeptide 1128:1139 arg1 spectra 1141:1147 glycopeptide spectra 1128:1147 glycopeptide spectra 1128:1147 Spectra of intact glycopeptides were selected by using glycan oxonium ions as signature ions for glycopeptide spectra. 25945896 4 49 theme dissociation 807:818 arg1 fragmentation 826:838 higher-energy collisional dissociation (HCD) fragmentation 781:838 higher-energy collisional dissociation (HCD) fragmentation of complex samples 781:857 Here, we report an algorithm, named GPQuest, for site-specific identification of intact glycopeptides using higher-energy collisional dissociation (HCD) fragmentation of complex samples. 25945896 10 50 theme MS/MS 1802:1806 arg1 spectra 1808:1814 1008 glycan-containing MS/MS spectra 1779:1814 1008 glycan-containing MS/MS spectra 1779:1814 Without enrichment of glycopeptides from global tryptic peptides and at a false discovery rate of 1%, 1008 glycan-containing MS/MS spectra were assigned to 769 unique intact N-linked glycopeptides, representing 344 N-linked glycosites with 57 different N-glycans. 25945896 5 51 theme glycosite-containing 901:920 arg1 peptides 922:929 glycosite-containing peptides 901:929 glycosite-containing peptides in the sample 901:943 In this algorithm, a spectral library of glycosite-containing peptides in the sample was built by analyzing the isolated glycosite-containing peptides using HCD LC-MS/MS. 25945896 7 52 theme glycosite-containing 1247:1266 arg1 peptides 1268:1275 glycosite-containing peptides 1247:1275 glycosite-containing peptides 1247:1275 These oxonium-ion-containing spectra were then compared with the spectral library generated from glycosite-containing peptides, resulting in assignment of each intact glycopeptide MS/MS spectrum to a specific glycosite-containing peptide. 25945896 10 53 with glycosites 1901:1910 arg1 N-glycans 1930:1938 57 different N-glycans 1917:1938 57 different N-glycans 1917:1938 Without enrichment of glycopeptides from global tryptic peptides and at a false discovery rate of 1%, 1008 glycan-containing MS/MS spectra were assigned to 769 unique intact N-linked glycopeptides, representing 344 N-linked glycosites with 57 different N-glycans. 25945896 2 54 theme intact 495:500 arg1 glycopeptides 502:514 intact glycopeptides 495:514 intact glycopeptides with glycans attached to each specific glycosylation site 495:572 Recent advances in mass spectrometry instrumentation and techniques have facilitated analysis of intact glycopeptides in complex biological samples by allowing the users to generate spectra of intact glycopeptides with glycans attached to each specific glycosylation site. 25945896 10 55 theme unique 1837:1842 arg1 glycopeptides 1860:1872 769 unique intact N-linked glycopeptides 1833:1872 769 unique intact N-linked glycopeptides 1833:1872 Without enrichment of glycopeptides from global tryptic peptides and at a false discovery rate of 1%, 1008 glycan-containing MS/MS spectra were assigned to 769 unique intact N-linked glycopeptides, representing 344 N-linked glycosites with 57 different N-glycans. 25945896 0 56 dep Library 20:26 arg1 GPQuest 0:6 GPQuest 0:6 GPQuest 0:6 GPQuest: A Spectral Library Matching Algorithm for Site-Specific Assignment of Tandem Mass Spectra to Intact N-glycopeptides. 25945896 6 57 gly glycopeptide 1128:1139 arg2 glycopeptide 1128:1139 glycopeptide spectra 1128:1147 glycopeptide spectra 1128:1147 Spectra of intact glycopeptides were selected by using glycan oxonium ions as signature ions for glycopeptide spectra. 25945896 4 58 theme complex 843:849 arg1 samples 851:857 complex samples 843:857 complex samples 843:857 Here, we report an algorithm, named GPQuest, for site-specific identification of intact glycopeptides using higher-energy collisional dissociation (HCD) fragmentation of complex samples. 25945896 11 59 theme HCD 1993:1995 arg1 spectra 2016:2022 the HCD LC-MS/MS generated spectra 1989:2022 the HCD LC-MS/MS generated spectra of intact glycopeptides 1989:2046 Spectral library matching using GPQuest assigns the HCD LC-MS/MS generated spectra of intact glycopeptides in an automated and high-throughput manner. 25945896 1 60 theme glycosylation 214:226 arg1 site 228:231 each glycosylation site 209:231 each glycosylation site 209:231 Glycoprotein changes occur in not only protein abundance but also the occupancy of each glycosylation site by different glycoforms during biological or pathological processes. 25945896 2 61 theme intact 399:404 arg1 glycopeptides 406:418 intact glycopeptides 399:418 intact glycopeptides in complex biological samples 399:448 Recent advances in mass spectrometry instrumentation and techniques have facilitated analysis of intact glycopeptides in complex biological samples by allowing the users to generate spectra of intact glycopeptides with glycans attached to each specific glycosylation site. 25945896 12 62 theme modified 2187:2194 arg1 glycans 2196:2202 novel or modified glycans 2178:2202 novel or modified glycans 2178:2202 Additionally, spectral library matching gives the user the possibility of identifying novel or modified glycans on specific glycosites that might be missing from the predetermined glycan databases. 25945896 7 63 theme glycopeptide 1317:1328 arg1 spectrum 1336:1343 each intact glycopeptide MS/MS spectrum 1305:1343 each intact glycopeptide MS/MS spectrum 1305:1343 These oxonium-ion-containing spectra were then compared with the spectral library generated from glycosite-containing peptides, resulting in assignment of each intact glycopeptide MS/MS spectrum to a specific glycosite-containing peptide. 25945896 10 64 theme N-linked 1851:1858 arg1 glycopeptides 1860:1872 769 unique intact N-linked glycopeptides 1833:1872 769 unique intact N-linked glycopeptides 1833:1872 Without enrichment of glycopeptides from global tryptic peptides and at a false discovery rate of 1%, 1008 glycan-containing MS/MS spectra were assigned to 769 unique intact N-linked glycopeptides, representing 344 N-linked glycosites with 57 different N-glycans. 25945896 7 65 theme specific 1350:1357 arg1 peptide 1380:1386 a specific glycosite-containing peptide 1348:1386 a specific glycosite-containing peptide 1348:1386 These oxonium-ion-containing spectra were then compared with the spectral library generated from glycosite-containing peptides, resulting in assignment of each intact glycopeptide MS/MS spectrum to a specific glycosite-containing peptide. 25945896 10 66 theme tryptic 1725:1731 arg1 peptides 1733:1740 global tryptic peptides 1718:1740 global tryptic peptides 1718:1740 Without enrichment of glycopeptides from global tryptic peptides and at a false discovery rate of 1%, 1008 glycan-containing MS/MS spectra were assigned to 769 unique intact N-linked glycopeptides, representing 344 N-linked glycosites with 57 different N-glycans. 25945896 2 67 theme Recent 302:307 arg1 advances 309:316 Recent advances 302:316 Recent advances in mass spectrometry instrumentation and techniques 302:368 Recent advances in mass spectrometry instrumentation and techniques have facilitated analysis of intact glycopeptides in complex biological samples by allowing the users to generate spectra of intact glycopeptides with glycans attached to each specific glycosylation site. 25945896 2 68 with glycopeptides 502:514 arg1 glycans 521:527 glycans 521:527 glycans attached to each specific glycosylation site 521:572 Recent advances in mass spectrometry instrumentation and techniques have facilitated analysis of intact glycopeptides in complex biological samples by allowing the users to generate spectra of intact glycopeptides with glycans attached to each specific glycosylation site. 25945896 1 69 theme biological 264:273 arg1 processes 291:299 biological or pathological processes 264:299 biological or pathological processes 264:299 Glycoprotein changes occur in not only protein abundance but also the occupancy of each glycosylation site by different glycoforms during biological or pathological processes. 25945896 8 70 theme mass 1456:1459 arg1 difference 1461:1470 the mass difference 1452:1470 the mass difference between the precursor ion of intact glycopeptide and the glycosite-containing peptide to a glycan database 1452:1577 The glycan occupying each glycosite was determined by matching the mass difference between the precursor ion of intact glycopeptide and the glycosite-containing peptide to a glycan database. 25945896 11 71 theme generated 2006:2014 arg1 spectra 2016:2022 the HCD LC-MS/MS generated spectra 1989:2022 the HCD LC-MS/MS generated spectra of intact glycopeptides 1989:2046 Spectral library matching using GPQuest assigns the HCD LC-MS/MS generated spectra of intact glycopeptides in an automated and high-throughput manner. 25945896 1 72 gly occupancy 196:204 arg2 site 228:231 each glycosylation site 209:231 each glycosylation site 209:231 Glycoprotein changes occur in not only protein abundance but also the occupancy of each glycosylation site by different glycoforms during biological or pathological processes. 25945896 1 73 theme protein 165:171 arg1 abundance 173:181 protein abundance 165:181 not only protein abundance but also the occupancy of each glycosylation site by different glycoforms 156:255 Glycoprotein changes occur in not only protein abundance but also the occupancy of each glycosylation site by different glycoforms during biological or pathological processes. 25945896 12 74 theme novel 2178:2182 arg1 glycans 2196:2202 novel or modified glycans 2178:2202 novel or modified glycans 2178:2202 Additionally, spectral library matching gives the user the possibility of identifying novel or modified glycans on specific glycosites that might be missing from the predetermined glycan databases. 25945896 2 75 from analysis 387:394 arg1 samples 442:448 complex biological samples 423:448 complex biological samples 423:448 Recent advances in mass spectrometry instrumentation and techniques have facilitated analysis of intact glycopeptides in complex biological samples by allowing the users to generate spectra of intact glycopeptides with glycans attached to each specific glycosylation site. 25945896 7 76 theme oxonium-ion-containing 1156:1177 arg1 spectra 1179:1185 These oxonium-ion-containing spectra 1150:1185 These oxonium-ion-containing spectra 1150:1185 These oxonium-ion-containing spectra were then compared with the spectral library generated from glycosite-containing peptides, resulting in assignment of each intact glycopeptide MS/MS spectrum to a specific glycosite-containing peptide. 25945896 2 77 theme spectrometry 326:337 arg1 instrumentation 339:353 mass spectrometry instrumentation 321:353 mass spectrometry instrumentation 321:353 Recent advances in mass spectrometry instrumentation and techniques have facilitated analysis of intact glycopeptides in complex biological samples by allowing the users to generate spectra of intact glycopeptides with glycans attached to each specific glycosylation site. 25945896 6 78 theme intact 1042:1047 arg1 glycopeptides 1049:1061 intact glycopeptides 1042:1061 intact glycopeptides 1042:1061 Spectra of intact glycopeptides were selected by using glycan oxonium ions as signature ions for glycopeptide spectra. 25945896 11 79 theme matching 1958:1965 arg1 library 1950:1956 Spectral library matching 1941:1965 Spectral library matching using GPQuest 1941:1979 Spectral library matching using GPQuest assigns the HCD LC-MS/MS generated spectra of intact glycopeptides in an automated and high-throughput manner. 25945896 4 80 theme samples 851:857 arg1 fragmentation 826:838 higher-energy collisional dissociation (HCD) fragmentation 781:838 higher-energy collisional dissociation (HCD) fragmentation of complex samples 781:857 Here, we report an algorithm, named GPQuest, for site-specific identification of intact glycopeptides using higher-energy collisional dissociation (HCD) fragmentation of complex samples. 25945896 12 81 theme glycan 2272:2277 arg1 databases 2279:2287 the predetermined glycan databases 2254:2287 the predetermined glycan databases 2254:2287 Additionally, spectral library matching gives the user the possibility of identifying novel or modified glycans on specific glycosites that might be missing from the predetermined glycan databases. 25945896 10 82 link N-linked 1892:1899 arg1 glycosites 1901:1910 344 N-linked glycosites 1888:1910 344 N-linked glycosites with 57 different N-glycans 1888:1938 Without enrichment of glycopeptides from global tryptic peptides and at a false discovery rate of 1%, 1008 glycan-containing MS/MS spectra were assigned to 769 unique intact N-linked glycopeptides, representing 344 N-linked glycosites with 57 different N-glycans. 25945896 9 83 theme LC-MS/MS 1607:1614 arg1 spectra 1616:1622 LC-MS/MS spectra 1607:1622 LC-MS/MS spectra of protein extracts from prostate tumor LNCaP cells 1607:1674 Using GPQuest, we analyzed LC-MS/MS spectra of protein extracts from prostate tumor LNCaP cells. 25945896 12 84 theme spectral 2106:2113 arg1 library 2115:2121 spectral library 2106:2121 spectral library matching 2106:2130 Additionally, spectral library matching gives the user the possibility of identifying novel or modified glycans on specific glycosites that might be missing from the predetermined glycan databases. 25945896 10 85 theme discovery 1757:1765 arg1 rate 1767:1770 a false discovery rate 1749:1770 a false discovery rate of 1% 1749:1776 Without enrichment of glycopeptides from global tryptic peptides and at a false discovery rate of 1%, 1008 glycan-containing MS/MS spectra were assigned to 769 unique intact N-linked glycopeptides, representing 344 N-linked glycosites with 57 different N-glycans. 25945896 0 86 gly N-glycopeptides 109:123 arg2 N-glycopeptides 109:123 Intact N-glycopeptides 102:123 Intact N-glycopeptides 102:123 GPQuest: A Spectral Library Matching Algorithm for Site-Specific Assignment of Tandem Mass Spectra to Intact N-glycopeptides. 25945896 10 87 gly glycopeptides 1699:1711 arg1 peptides 1733:1740 global tryptic peptides 1718:1740 global tryptic peptides 1718:1740 Without enrichment of glycopeptides from global tryptic peptides and at a false discovery rate of 1%, 1008 glycan-containing MS/MS spectra were assigned to 769 unique intact N-linked glycopeptides, representing 344 N-linked glycosites with 57 different N-glycans. 25945896 10 87 gly glycopeptides 1699:1711 arg2 glycopeptides 1699:1711 glycopeptides 1699:1711 glycopeptides from global tryptic peptides 1699:1740 Without enrichment of glycopeptides from global tryptic peptides and at a false discovery rate of 1%, 1008 glycan-containing MS/MS spectra were assigned to 769 unique intact N-linked glycopeptides, representing 344 N-linked glycosites with 57 different N-glycans. 25945896 5 88 theme isolated 972:979 arg1 peptides 1002:1009 the isolated glycosite-containing peptides 968:1009 the isolated glycosite-containing peptides using HCD LC-MS/MS 968:1028 In this algorithm, a spectral library of glycosite-containing peptides in the sample was built by analyzing the isolated glycosite-containing peptides using HCD LC-MS/MS. 25945896 5 89 from peptides 922:929 arg1 sample 938:943 the sample 934:943 the sample 934:943 In this algorithm, a spectral library of glycosite-containing peptides in the sample was built by analyzing the isolated glycosite-containing peptides using HCD LC-MS/MS. 25945896 4 90 theme intact 754:759 arg1 glycopeptides 761:773 intact glycopeptides 754:773 intact glycopeptides using higher-energy collisional dissociation (HCD) fragmentation of complex samples 754:857 Here, we report an algorithm, named GPQuest, for site-specific identification of intact glycopeptides using higher-energy collisional dissociation (HCD) fragmentation of complex samples. 25945896 7 91 theme spectrum 1336:1343 arg1 assignment 1291:1300 assignment 1291:1300 assignment of each intact glycopeptide MS/MS spectrum to a specific glycosite-containing peptide 1291:1386 These oxonium-ion-containing spectra were then compared with the spectral library generated from glycosite-containing peptides, resulting in assignment of each intact glycopeptide MS/MS spectrum to a specific glycosite-containing peptide. 25945896 9 92 theme prostate 1649:1656 arg1 cells 1670:1674 prostate tumor LNCaP cells 1649:1674 prostate tumor LNCaP cells 1649:1674 Using GPQuest, we analyzed LC-MS/MS spectra of protein extracts from prostate tumor LNCaP cells. 25945896 6 93 theme glycan 1086:1091 arg1 ions 1119:1122 signature ions 1109:1122 signature ions for glycopeptide spectra 1109:1147 Spectra of intact glycopeptides were selected by using glycan oxonium ions as signature ions for glycopeptide spectra. 25945896 6 93 theme glycan 1086:1091 arg1 ions 1101:1104 glycan oxonium ions 1086:1104 glycan oxonium ions 1086:1104 Spectra of intact glycopeptides were selected by using glycan oxonium ions as signature ions for glycopeptide spectra. 25945896 7 94 theme intact 1310:1315 arg1 spectrum 1336:1343 each intact glycopeptide MS/MS spectrum 1305:1343 each intact glycopeptide MS/MS spectrum 1305:1343 These oxonium-ion-containing spectra were then compared with the spectral library generated from glycosite-containing peptides, resulting in assignment of each intact glycopeptide MS/MS spectrum to a specific glycosite-containing peptide. 25945896 0 95 theme Tandem 79:84 arg1 Spectra 91:97 Tandem Mass Spectra 79:97 Tandem Mass Spectra 79:97 GPQuest: A Spectral Library Matching Algorithm for Site-Specific Assignment of Tandem Mass Spectra to Intact N-glycopeptides. 25945896 8 96 gly glycosite 1415:1423 arg2 glycosite 1415:1423 each glycosite 1410:1423 each glycosite 1410:1423 The glycan occupying each glycosite was determined by matching the mass difference between the precursor ion of intact glycopeptide and the glycosite-containing peptide to a glycan database. 25945896 2 97 attach attached 529:536 arg2 glycans 521:527 glycans 521:527 glycans attached to each specific glycosylation site 521:572 Recent advances in mass spectrometry instrumentation and techniques have facilitated analysis of intact glycopeptides in complex biological samples by allowing the users to generate spectra of intact glycopeptides with glycans attached to each specific glycosylation site. 25945896 2 97 attach attached 529:536 arg1 site 569:572 each specific glycosylation site 541:572 each specific glycosylation site 541:572 Recent advances in mass spectrometry instrumentation and techniques have facilitated analysis of intact glycopeptides in complex biological samples by allowing the users to generate spectra of intact glycopeptides with glycans attached to each specific glycosylation site. 25945896 9 98 theme LNCaP 1664:1668 arg1 cells 1670:1674 prostate tumor LNCaP cells 1649:1674 prostate tumor LNCaP cells 1649:1674 Using GPQuest, we analyzed LC-MS/MS spectra of protein extracts from prostate tumor LNCaP cells. 25945896 2 99 from advances 309:316 arg1 techniques 359:368 techniques 359:368 techniques 359:368 Recent advances in mass spectrometry instrumentation and techniques have facilitated analysis of intact glycopeptides in complex biological samples by allowing the users to generate spectra of intact glycopeptides with glycans attached to each specific glycosylation site. 25945896 2 99 from advances 309:316 arg1 instrumentation 339:353 mass spectrometry instrumentation 321:353 mass spectrometry instrumentation 321:353 Recent advances in mass spectrometry instrumentation and techniques have facilitated analysis of intact glycopeptides in complex biological samples by allowing the users to generate spectra of intact glycopeptides with glycans attached to each specific glycosylation site. 25945896 0 100 theme Spectra 91:97 arg1 Assignment 65:74 Site-Specific Assignment 51:74 Site-Specific Assignment of Tandem Mass Spectra to Intact N-glycopeptides 51:123 GPQuest: A Spectral Library Matching Algorithm for Site-Specific Assignment of Tandem Mass Spectra to Intact N-glycopeptides. 25945896 1 101 gly glycosylation 214:226 arg2 site 228:231 each glycosylation site 209:231 each glycosylation site 209:231 Glycoprotein changes occur in not only protein abundance but also the occupancy of each glycosylation site by different glycoforms during biological or pathological processes. 25945896 0 102 theme Intact 102:107 arg1 N-glycopeptides 109:123 Intact N-glycopeptides 102:123 Intact N-glycopeptides 102:123 GPQuest: A Spectral Library Matching Algorithm for Site-Specific Assignment of Tandem Mass Spectra to Intact N-glycopeptides. 25945896 2 103 theme specific 546:553 arg1 site 569:572 each specific glycosylation site 541:572 each specific glycosylation site 541:572 Recent advances in mass spectrometry instrumentation and techniques have facilitated analysis of intact glycopeptides in complex biological samples by allowing the users to generate spectra of intact glycopeptides with glycans attached to each specific glycosylation site. 25945896 2 104 theme complex 423:429 arg1 samples 442:448 complex biological samples 423:448 complex biological samples 423:448 Recent advances in mass spectrometry instrumentation and techniques have facilitated analysis of intact glycopeptides in complex biological samples by allowing the users to generate spectra of intact glycopeptides with glycans attached to each specific glycosylation site. 25945896 11 105 theme Spectral 1941:1948 arg1 library 1950:1956 Spectral library matching 1941:1965 Spectral library matching using GPQuest 1941:1979 Spectral library matching using GPQuest assigns the HCD LC-MS/MS generated spectra of intact glycopeptides in an automated and high-throughput manner. 25945896 2 106 theme glycopeptides 406:418 arg1 analysis 387:394 analysis 387:394 analysis of intact glycopeptides in complex biological samples 387:448 Recent advances in mass spectrometry instrumentation and techniques have facilitated analysis of intact glycopeptides in complex biological samples by allowing the users to generate spectra of intact glycopeptides with glycans attached to each specific glycosylation site. 25945896 0 107 theme Spectral 11:18 arg1 Library 20:26 A Spectral Library 9:26 A Spectral Library Matching Algorithm for Site-Specific Assignment of Tandem Mass Spectra to Intact N-glycopeptides 9:123 GPQuest: A Spectral Library Matching Algorithm for Site-Specific Assignment of Tandem Mass Spectra to Intact N-glycopeptides. 25945896 5 108 theme HCD 1017:1019 arg1 LC-MS/MS 1021:1028 HCD LC-MS/MS 1017:1028 HCD LC-MS/MS 1017:1028 In this algorithm, a spectral library of glycosite-containing peptides in the sample was built by analyzing the isolated glycosite-containing peptides using HCD LC-MS/MS. 25945896 8 109 theme intact 1501:1506 arg1 glycopeptide 1508:1519 intact glycopeptide 1501:1519 intact glycopeptide 1501:1519 The glycan occupying each glycosite was determined by matching the mass difference between the precursor ion of intact glycopeptide and the glycosite-containing peptide to a glycan database. 25945896 11 110 theme glycopeptides 2034:2046 arg1 spectra 2016:2022 the HCD LC-MS/MS generated spectra 1989:2022 the HCD LC-MS/MS generated spectra of intact glycopeptides 1989:2046 Spectral library matching using GPQuest assigns the HCD LC-MS/MS generated spectra of intact glycopeptides in an automated and high-throughput manner. 25945896 2 111 gly glycopeptides 502:514 arg2 glycopeptides 502:514 intact glycopeptides 495:514 intact glycopeptides with glycans attached to each specific glycosylation site 495:572 Recent advances in mass spectrometry instrumentation and techniques have facilitated analysis of intact glycopeptides in complex biological samples by allowing the users to generate spectra of intact glycopeptides with glycans attached to each specific glycosylation site. 25945896 6 112 theme signature 1109:1117 arg1 ions 1119:1122 signature ions 1109:1122 signature ions for glycopeptide spectra 1109:1147 Spectra of intact glycopeptides were selected by using glycan oxonium ions as signature ions for glycopeptide spectra. 25945896 6 112 theme signature 1109:1117 arg1 ions 1101:1104 glycan oxonium ions 1086:1104 glycan oxonium ions 1086:1104 Spectra of intact glycopeptides were selected by using glycan oxonium ions as signature ions for glycopeptide spectra. 25945896 2 113 theme glycopeptides 502:514 arg1 spectra 484:490 spectra 484:490 spectra of intact glycopeptides with glycans attached to each specific glycosylation site 484:572 Recent advances in mass spectrometry instrumentation and techniques have facilitated analysis of intact glycopeptides in complex biological samples by allowing the users to generate spectra of intact glycopeptides with glycans attached to each specific glycosylation site. 25945896 10 114 theme glycan-containing 1784:1800 arg1 spectra 1808:1814 1008 glycan-containing MS/MS spectra 1779:1814 1008 glycan-containing MS/MS spectra 1779:1814 Without enrichment of glycopeptides from global tryptic peptides and at a false discovery rate of 1%, 1008 glycan-containing MS/MS spectra were assigned to 769 unique intact N-linked glycopeptides, representing 344 N-linked glycosites with 57 different N-glycans. 25945896 10 115 gly glycosites 1901:1910 arg2 glycosites 1901:1910 344 N-linked glycosites 1888:1910 344 N-linked glycosites with 57 different N-glycans 1888:1938 Without enrichment of glycopeptides from global tryptic peptides and at a false discovery rate of 1%, 1008 glycan-containing MS/MS spectra were assigned to 769 unique intact N-linked glycopeptides, representing 344 N-linked glycosites with 57 different N-glycans. 25945896 10 116 from enrichment 1685:1694 arg1 peptides 1733:1740 global tryptic peptides 1718:1740 global tryptic peptides 1718:1740 Without enrichment of glycopeptides from global tryptic peptides and at a false discovery rate of 1%, 1008 glycan-containing MS/MS spectra were assigned to 769 unique intact N-linked glycopeptides, representing 344 N-linked glycosites with 57 different N-glycans. 25945896 2 117 from glycopeptides 406:418 arg1 samples 442:448 complex biological samples 423:448 complex biological samples 423:448 Recent advances in mass spectrometry instrumentation and techniques have facilitated analysis of intact glycopeptides in complex biological samples by allowing the users to generate spectra of intact glycopeptides with glycans attached to each specific glycosylation site. 25945896 8 118 theme glycosite-containing 1529:1548 arg1 peptide 1550:1556 the glycosite-containing peptide 1525:1556 the glycosite-containing peptide to a glycan database 1525:1577 The glycan occupying each glycosite was determined by matching the mass difference between the precursor ion of intact glycopeptide and the glycosite-containing peptide to a glycan database. 25945896 6 119 gly glycopeptides 1049:1061 arg2 glycopeptides 1049:1061 intact glycopeptides 1042:1061 intact glycopeptides 1042:1061 Spectra of intact glycopeptides were selected by using glycan oxonium ions as signature ions for glycopeptide spectra. 25945896 8 120 gly glycopeptide 1508:1519 arg2 glycopeptide 1508:1519 intact glycopeptide 1501:1519 intact glycopeptide 1501:1519 The glycan occupying each glycosite was determined by matching the mass difference between the precursor ion of intact glycopeptide and the glycosite-containing peptide to a glycan database. 25945896 11 121 theme LC-MS/MS 1997:2004 arg1 spectra 2016:2022 the HCD LC-MS/MS generated spectra 1989:2022 the HCD LC-MS/MS generated spectra of intact glycopeptides 1989:2046 Spectral library matching using GPQuest assigns the HCD LC-MS/MS generated spectra of intact glycopeptides in an automated and high-throughput manner. 25945896 1 122 theme site 228:231 arg1 occupancy 196:204 the occupancy 192:204 not only protein abundance but also the occupancy of each glycosylation site by different glycoforms 156:255 Glycoprotein changes occur in not only protein abundance but also the occupancy of each glycosylation site by different glycoforms during biological or pathological processes. 25945896 1 122 theme site 228:231 arg1 abundance 173:181 protein abundance 165:181 not only protein abundance but also the occupancy of each glycosylation site by different glycoforms 156:255 Glycoprotein changes occur in not only protein abundance but also the occupancy of each glycosylation site by different glycoforms during biological or pathological processes. 25945896 2 123 from samples 442:448 arg1 analysis 387:394 analysis 387:394 analysis of intact glycopeptides in complex biological samples 387:448 Recent advances in mass spectrometry instrumentation and techniques have facilitated analysis of intact glycopeptides in complex biological samples by allowing the users to generate spectra of intact glycopeptides with glycans attached to each specific glycosylation site. 25945896 7 124 theme glycosite-containing 1359:1378 arg1 peptide 1380:1386 a specific glycosite-containing peptide 1348:1386 a specific glycosite-containing peptide 1348:1386 These oxonium-ion-containing spectra were then compared with the spectral library generated from glycosite-containing peptides, resulting in assignment of each intact glycopeptide MS/MS spectrum to a specific glycosite-containing peptide. 25945896 11 125 theme high-throughput 2068:2082 arg1 manner 2084:2089 an automated and high-throughput manner 2051:2089 an automated and high-throughput manner 2051:2089 Spectral library matching using GPQuest assigns the HCD LC-MS/MS generated spectra of intact glycopeptides in an automated and high-throughput manner. 25945896 12 126 theme predetermined 2258:2270 arg1 databases 2279:2287 the predetermined glycan databases 2254:2287 the predetermined glycan databases 2254:2287 Additionally, spectral library matching gives the user the possibility of identifying novel or modified glycans on specific glycosites that might be missing from the predetermined glycan databases. 25945896 8 127 theme glycan 1563:1568 arg1 database 1570:1577 a glycan database 1561:1577 a glycan database 1561:1577 The glycan occupying each glycosite was determined by matching the mass difference between the precursor ion of intact glycopeptide and the glycosite-containing peptide to a glycan database. 25945896 1 128 theme different 236:244 arg1 glycoforms 246:255 different glycoforms 236:255 different glycoforms 236:255 Glycoprotein changes occur in not only protein abundance but also the occupancy of each glycosylation site by different glycoforms during biological or pathological processes. 28973932 4 0 theme cdh 957:959 arg1 loss 949:952 specific loss 940:952 specific loss of cdh and pcdh O-Man glycosylation 940:988 KO of all four TMTC genes in HEK293 cells resulted in specific loss of cdh and pcdh O-Man glycosylation, whereas combined KO of TMTC1 and TMTC3 resulted in selective loss of O-Man glycans on specific β-strands of EC domains, suggesting that each isoenzyme serves a different function. 28973932 1 1 theme mannose 158:164 arg1 glycans 174:180 O-linked mannose (O-Man) glycans 149:180 O-linked mannose (O-Man) glycans 149:180 The cadherin (cdh) superfamily of adhesion molecules carry O-linked mannose (O-Man) glycans at highly conserved sites localized to specific β-strands of their extracellular cdh (EC) domains. 28973932 5 2 theme glycosylation 1353:1365 arg1 machinery 1367:1375 yet another O-Man glycosylation machinery 1335:1375 yet another O-Man glycosylation machinery 1335:1375 In addition, O-Man glycosylation of IPT/TIG domains of plexins and hepatocyte growth factor receptor was not affected in TMTC KO cells, suggesting the existence of yet another O-Man glycosylation machinery. 28973932 2 3 theme pcdh 449:452 arg1 glycosylation 461:473 cdh/protocadherin (pcdh) O-Man glycosylation 430:473 cdh/protocadherin (pcdh) O-Man glycosylation 430:473 These O-Man glycans do not appear to be elongated like O-Man glycans found on α-dystroglycan (α-DG), and we recently demonstrated that initiation of cdh/protocadherin (pcdh) O-Man glycosylation is not dependent on the evolutionary conserved POMT1/POMT2 enzymes that initiate O-Man glycosylation on α-DG. 28973932 4 4 theme TMTC3 1024:1028 arg1 KO 1008:1009 combined KO 999:1009 combined KO of TMTC1 and TMTC3 999:1028 KO of all four TMTC genes in HEK293 cells resulted in specific loss of cdh and pcdh O-Man glycosylation, whereas combined KO of TMTC1 and TMTC3 resulted in selective loss of O-Man glycans on specific β-strands of EC domains, suggesting that each isoenzyme serves a different function. 28973932 1 5 theme extracellular 249:261 arg1 domains 272:278 their extracellular cdh (EC) domains 243:278 their extracellular cdh (EC) domains 243:278 The cadherin (cdh) superfamily of adhesion molecules carry O-linked mannose (O-Man) glycans at highly conserved sites localized to specific β-strands of their extracellular cdh (EC) domains. 28973932 3 6 theme quantitative 669:680 arg1 glycoproteomics 688:702 sensitive and quantitative O-Man glycoproteomics 655:702 sensitive and quantitative O-Man glycoproteomics 655:702 Here, we used a CRISPR/Cas9 genetic dissection strategy combined with sensitive and quantitative O-Man glycoproteomics to identify a homologous family of four putative protein O-mannosyltransferases encoded by the TMTC1-4 genes, which were found to be imperative for cdh and pcdh O-Man glycosylation. 28973932 5 7 theme IPT/TIG 1207:1213 arg1 domains 1215:1221 IPT/TIG domains 1207:1221 IPT/TIG domains of plexins and hepatocyte growth factor receptor 1207:1270 In addition, O-Man glycosylation of IPT/TIG domains of plexins and hepatocyte growth factor receptor was not affected in TMTC KO cells, suggesting the existence of yet another O-Man glycosylation machinery. 28973932 5 7 theme IPT/TIG 1207:1213 arg1 receptor 1263:1270 hepatocyte growth factor receptor 1238:1270 hepatocyte growth factor receptor 1238:1270 In addition, O-Man glycosylation of IPT/TIG domains of plexins and hepatocyte growth factor receptor was not affected in TMTC KO cells, suggesting the existence of yet another O-Man glycosylation machinery. 28973932 5 7 theme IPT/TIG 1207:1213 arg1 plexins 1226:1232 plexins 1226:1232 plexins 1226:1232 In addition, O-Man glycosylation of IPT/TIG domains of plexins and hepatocyte growth factor receptor was not affected in TMTC KO cells, suggesting the existence of yet another O-Man glycosylation machinery. 28973932 6 8 theme higher 1439:1444 arg1 eukaryotes 1446:1455 higher eukaryotes 1439:1455 higher eukaryotes 1439:1455 Our study demonstrates that regulation of O-mannosylation in higher eukaryotes is more complex than envisioned, and the discovery of the functions of TMTCs provide insight into cobblestone lissencephaly caused by deficiency in TMTC3. 28973932 5 9 theme TMTC 1292:1295 arg1 cells 1300:1304 TMTC KO cells 1292:1304 TMTC KO cells 1292:1304 In addition, O-Man glycosylation of IPT/TIG domains of plexins and hepatocyte growth factor receptor was not affected in TMTC KO cells, suggesting the existence of yet another O-Man glycosylation machinery. 28973932 1 10 theme cdh 263:265 arg1 domains 272:278 their extracellular cdh (EC) domains 243:278 their extracellular cdh (EC) domains 243:278 The cadherin (cdh) superfamily of adhesion molecules carry O-linked mannose (O-Man) glycans at highly conserved sites localized to specific β-strands of their extracellular cdh (EC) domains. 28973932 4 11 theme HEK293 915:920 arg1 cells 922:926 HEK293 cells 915:926 HEK293 cells 915:926 KO of all four TMTC genes in HEK293 cells resulted in specific loss of cdh and pcdh O-Man glycosylation, whereas combined KO of TMTC1 and TMTC3 resulted in selective loss of O-Man glycans on specific β-strands of EC domains, suggesting that each isoenzyme serves a different function. 28973932 5 12 gly glycosylation 1190:1202 arg1 domains 1215:1221 IPT/TIG domains 1207:1221 IPT/TIG domains of plexins and hepatocyte growth factor receptor 1207:1270 In addition, O-Man glycosylation of IPT/TIG domains of plexins and hepatocyte growth factor receptor was not affected in TMTC KO cells, suggesting the existence of yet another O-Man glycosylation machinery. 28973932 5 12 gly glycosylation 1190:1202 arg1 cells 1300:1304 TMTC KO cells 1292:1304 TMTC KO cells 1292:1304 In addition, O-Man glycosylation of IPT/TIG domains of plexins and hepatocyte growth factor receptor was not affected in TMTC KO cells, suggesting the existence of yet another O-Man glycosylation machinery. 28973932 5 12 gly glycosylation 1190:1202 arg1 plexins 1226:1232 plexins 1226:1232 plexins 1226:1232 In addition, O-Man glycosylation of IPT/TIG domains of plexins and hepatocyte growth factor receptor was not affected in TMTC KO cells, suggesting the existence of yet another O-Man glycosylation machinery. 28973932 5 12 gly glycosylation 1190:1202 arg1 addition 1174:1181 addition 1174:1181 addition 1174:1181 In addition, O-Man glycosylation of IPT/TIG domains of plexins and hepatocyte growth factor receptor was not affected in TMTC KO cells, suggesting the existence of yet another O-Man glycosylation machinery. 28973932 5 12 gly glycosylation 1190:1202 arg1 receptor 1263:1270 hepatocyte growth factor receptor 1238:1270 hepatocyte growth factor receptor 1238:1270 In addition, O-Man glycosylation of IPT/TIG domains of plexins and hepatocyte growth factor receptor was not affected in TMTC KO cells, suggesting the existence of yet another O-Man glycosylation machinery. 28973932 3 13 used used 594:597 arg2 we 591:592 we 591:592 we 591:592 Here, we used a CRISPR/Cas9 genetic dissection strategy combined with sensitive and quantitative O-Man glycoproteomics to identify a homologous family of four putative protein O-mannosyltransferases encoded by the TMTC1-4 genes, which were found to be imperative for cdh and pcdh O-Man glycosylation. 28973932 3 14 theme homologous 718:727 arg1 family 729:734 a homologous family 716:734 a homologous family of four putative protein O-mannosyltransferases encoded by the TMTC1-4 genes, which were found to be imperative for cdh and pcdh O-Man glycosylation 716:883 Here, we used a CRISPR/Cas9 genetic dissection strategy combined with sensitive and quantitative O-Man glycoproteomics to identify a homologous family of four putative protein O-mannosyltransferases encoded by the TMTC1-4 genes, which were found to be imperative for cdh and pcdh O-Man glycosylation. 28973932 3 15 dep cdh 852:854 arg1 glycosylation 871:883 O-Man glycosylation 865:883 O-Man glycosylation 865:883 Here, we used a CRISPR/Cas9 genetic dissection strategy combined with sensitive and quantitative O-Man glycoproteomics to identify a homologous family of four putative protein O-mannosyltransferases encoded by the TMTC1-4 genes, which were found to be imperative for cdh and pcdh O-Man glycosylation. 28973932 4 16 theme specific 1077:1084 arg1 β-strands 1086:1094 specific β-strands 1077:1094 specific β-strands of EC domains 1077:1108 KO of all four TMTC genes in HEK293 cells resulted in specific loss of cdh and pcdh O-Man glycosylation, whereas combined KO of TMTC1 and TMTC3 resulted in selective loss of O-Man glycans on specific β-strands of EC domains, suggesting that each isoenzyme serves a different function. 28973932 1 17 theme O-Man 167:171 arg1 glycans 174:180 O-linked mannose (O-Man) glycans 149:180 O-linked mannose (O-Man) glycans 149:180 The cadherin (cdh) superfamily of adhesion molecules carry O-linked mannose (O-Man) glycans at highly conserved sites localized to specific β-strands of their extracellular cdh (EC) domains. 28973932 4 18 theme O-Man 970:974 arg1 glycosylation 976:988 pcdh O-Man glycosylation 965:988 pcdh O-Man glycosylation 965:988 KO of all four TMTC genes in HEK293 cells resulted in specific loss of cdh and pcdh O-Man glycosylation, whereas combined KO of TMTC1 and TMTC3 resulted in selective loss of O-Man glycans on specific β-strands of EC domains, suggesting that each isoenzyme serves a different function. 28973932 5 19 theme O-Man 1347:1351 arg1 machinery 1367:1375 yet another O-Man glycosylation machinery 1335:1375 yet another O-Man glycosylation machinery 1335:1375 In addition, O-Man glycosylation of IPT/TIG domains of plexins and hepatocyte growth factor receptor was not affected in TMTC KO cells, suggesting the existence of yet another O-Man glycosylation machinery. 28973932 4 20 theme EC 1099:1100 arg1 domains 1102:1108 EC domains 1099:1108 EC domains 1099:1108 KO of all four TMTC genes in HEK293 cells resulted in specific loss of cdh and pcdh O-Man glycosylation, whereas combined KO of TMTC1 and TMTC3 resulted in selective loss of O-Man glycans on specific β-strands of EC domains, suggesting that each isoenzyme serves a different function. 28973932 4 21 theme specific 940:947 arg1 loss 949:952 specific loss 940:952 specific loss of cdh and pcdh O-Man glycosylation 940:988 KO of all four TMTC genes in HEK293 cells resulted in specific loss of cdh and pcdh O-Man glycosylation, whereas combined KO of TMTC1 and TMTC3 resulted in selective loss of O-Man glycans on specific β-strands of EC domains, suggesting that each isoenzyme serves a different function. 28973932 5 22 theme domains 1215:1221 arg1 glycosylation 1190:1202 O-Man glycosylation 1184:1202 O-Man glycosylation of IPT/TIG domains of plexins and hepatocyte growth factor receptor 1184:1270 In addition, O-Man glycosylation of IPT/TIG domains of plexins and hepatocyte growth factor receptor was not affected in TMTC KO cells, suggesting the existence of yet another O-Man glycosylation machinery. 28973932 1 23 contain carry 143:147 arg1 superfamily 109:119 The cadherin (cdh) superfamily 90:119 The cadherin (cdh) superfamily of adhesion molecules 90:141 The cadherin (cdh) superfamily of adhesion molecules carry O-linked mannose (O-Man) glycans at highly conserved sites localized to specific β-strands of their extracellular cdh (EC) domains. 28973932 1 23 contain carry 143:147 arg3 sites 202:206 highly conserved sites 185:206 highly conserved sites localized to specific β-strands of their extracellular cdh (EC) domains 185:278 The cadherin (cdh) superfamily of adhesion molecules carry O-linked mannose (O-Man) glycans at highly conserved sites localized to specific β-strands of their extracellular cdh (EC) domains. 28973932 1 23 contain carry 143:147 arg2 glycans 174:180 O-linked mannose (O-Man) glycans 149:180 O-linked mannose (O-Man) glycans 149:180 The cadherin (cdh) superfamily of adhesion molecules carry O-linked mannose (O-Man) glycans at highly conserved sites localized to specific β-strands of their extracellular cdh (EC) domains. 28973932 6 24 theme O-mannosylation 1420:1434 arg1 regulation 1406:1415 regulation 1406:1415 regulation of O-mannosylation in higher eukaryotes 1406:1455 Our study demonstrates that regulation of O-mannosylation in higher eukaryotes is more complex than envisioned, and the discovery of the functions of TMTCs provide insight into cobblestone lissencephaly caused by deficiency in TMTC3. 28973932 4 25 theme different 1151:1159 arg1 function 1161:1168 a different function 1149:1168 a different function 1149:1168 KO of all four TMTC genes in HEK293 cells resulted in specific loss of cdh and pcdh O-Man glycosylation, whereas combined KO of TMTC1 and TMTC3 resulted in selective loss of O-Man glycans on specific β-strands of EC domains, suggesting that each isoenzyme serves a different function. 28973932 1 26 theme cadherin 94:101 arg1 superfamily 109:119 The cadherin (cdh) superfamily 90:119 The cadherin (cdh) superfamily of adhesion molecules 90:141 The cadherin (cdh) superfamily of adhesion molecules carry O-linked mannose (O-Man) glycans at highly conserved sites localized to specific β-strands of their extracellular cdh (EC) domains. 28973932 5 27 theme KO 1297:1298 arg1 cells 1300:1304 TMTC KO cells 1292:1304 TMTC KO cells 1292:1304 In addition, O-Man glycosylation of IPT/TIG domains of plexins and hepatocyte growth factor receptor was not affected in TMTC KO cells, suggesting the existence of yet another O-Man glycosylation machinery. 28973932 1 28 theme EC 268:269 arg1 domains 272:278 their extracellular cdh (EC) domains 243:278 their extracellular cdh (EC) domains 243:278 The cadherin (cdh) superfamily of adhesion molecules carry O-linked mannose (O-Man) glycans at highly conserved sites localized to specific β-strands of their extracellular cdh (EC) domains. 28973932 5 29 theme machinery 1367:1375 arg1 existence 1322:1330 the existence 1318:1330 the existence of yet another O-Man glycosylation machinery 1318:1375 In addition, O-Man glycosylation of IPT/TIG domains of plexins and hepatocyte growth factor receptor was not affected in TMTC KO cells, suggesting the existence of yet another O-Man glycosylation machinery. 28973932 4 30 theme O-Man 1060:1064 arg1 glycans 1066:1072 O-Man glycans 1060:1072 O-Man glycans 1060:1072 KO of all four TMTC genes in HEK293 cells resulted in specific loss of cdh and pcdh O-Man glycosylation, whereas combined KO of TMTC1 and TMTC3 resulted in selective loss of O-Man glycans on specific β-strands of EC domains, suggesting that each isoenzyme serves a different function. 28973932 0 31 theme O-mannosylation 16:30 arg1 pathway 32:38 an O-mannosylation pathway 13:38 an O-mannosylation pathway 13:38 Discovery of an O-mannosylation pathway selectively serving cadherins and protocadherins. 28973932 3 32 theme putative 744:751 arg1 O-mannosyltransferases 761:782 four putative protein O-mannosyltransferases 739:782 four putative protein O-mannosyltransferases encoded by the TMTC1-4 genes, which were found to be imperative for cdh and pcdh O-Man glycosylation 739:883 Here, we used a CRISPR/Cas9 genetic dissection strategy combined with sensitive and quantitative O-Man glycoproteomics to identify a homologous family of four putative protein O-mannosyltransferases encoded by the TMTC1-4 genes, which were found to be imperative for cdh and pcdh O-Man glycosylation. 28973932 2 33 theme POMT1/POMT2 522:532 arg1 enzymes 534:540 the evolutionary conserved POMT1/POMT2 enzymes 495:540 the evolutionary conserved POMT1/POMT2 enzymes that initiate O-Man glycosylation on α-DG 495:582 These O-Man glycans do not appear to be elongated like O-Man glycans found on α-dystroglycan (α-DG), and we recently demonstrated that initiation of cdh/protocadherin (pcdh) O-Man glycosylation is not dependent on the evolutionary conserved POMT1/POMT2 enzymes that initiate O-Man glycosylation on α-DG. 28973932 1 34 theme cdh 104:106 arg1 superfamily 109:119 The cadherin (cdh) superfamily 90:119 The cadherin (cdh) superfamily of adhesion molecules 90:141 The cadherin (cdh) superfamily of adhesion molecules carry O-linked mannose (O-Man) glycans at highly conserved sites localized to specific β-strands of their extracellular cdh (EC) domains. 28973932 5 35 theme receptor 1263:1270 arg1 domains 1215:1221 IPT/TIG domains 1207:1221 IPT/TIG domains of plexins and hepatocyte growth factor receptor 1207:1270 In addition, O-Man glycosylation of IPT/TIG domains of plexins and hepatocyte growth factor receptor was not affected in TMTC KO cells, suggesting the existence of yet another O-Man glycosylation machinery. 28973932 5 35 theme receptor 1263:1270 arg1 receptor 1263:1270 hepatocyte growth factor receptor 1238:1270 hepatocyte growth factor receptor 1238:1270 In addition, O-Man glycosylation of IPT/TIG domains of plexins and hepatocyte growth factor receptor was not affected in TMTC KO cells, suggesting the existence of yet another O-Man glycosylation machinery. 28973932 5 35 theme receptor 1263:1270 arg1 plexins 1226:1232 plexins 1226:1232 plexins 1226:1232 In addition, O-Man glycosylation of IPT/TIG domains of plexins and hepatocyte growth factor receptor was not affected in TMTC KO cells, suggesting the existence of yet another O-Man glycosylation machinery. 28973932 4 36 theme combined 999:1006 arg1 KO 1008:1009 combined KO 999:1009 combined KO of TMTC1 and TMTC3 999:1028 KO of all four TMTC genes in HEK293 cells resulted in specific loss of cdh and pcdh O-Man glycosylation, whereas combined KO of TMTC1 and TMTC3 resulted in selective loss of O-Man glycans on specific β-strands of EC domains, suggesting that each isoenzyme serves a different function. 28973932 1 37 theme domains 272:278 arg1 β-strands 230:238 specific β-strands 221:238 specific β-strands of their extracellular cdh (EC) domains 221:278 The cadherin (cdh) superfamily of adhesion molecules carry O-linked mannose (O-Man) glycans at highly conserved sites localized to specific β-strands of their extracellular cdh (EC) domains. 28973932 2 38 theme conserved 512:520 arg1 enzymes 534:540 the evolutionary conserved POMT1/POMT2 enzymes 495:540 the evolutionary conserved POMT1/POMT2 enzymes that initiate O-Man glycosylation on α-DG 495:582 These O-Man glycans do not appear to be elongated like O-Man glycans found on α-dystroglycan (α-DG), and we recently demonstrated that initiation of cdh/protocadherin (pcdh) O-Man glycosylation is not dependent on the evolutionary conserved POMT1/POMT2 enzymes that initiate O-Man glycosylation on α-DG. 28973932 3 39 theme genetic 613:619 arg1 strategy 632:639 a CRISPR/Cas9 genetic dissection strategy 599:639 a CRISPR/Cas9 genetic dissection strategy combined with sensitive and quantitative O-Man glycoproteomics 599:702 Here, we used a CRISPR/Cas9 genetic dissection strategy combined with sensitive and quantitative O-Man glycoproteomics to identify a homologous family of four putative protein O-mannosyltransferases encoded by the TMTC1-4 genes, which were found to be imperative for cdh and pcdh O-Man glycosylation. 28973932 1 40 theme conserved 192:200 arg1 sites 202:206 highly conserved sites 185:206 highly conserved sites localized to specific β-strands of their extracellular cdh (EC) domains 185:278 The cadherin (cdh) superfamily of adhesion molecules carry O-linked mannose (O-Man) glycans at highly conserved sites localized to specific β-strands of their extracellular cdh (EC) domains. 28973932 4 41 theme pcdh 965:968 arg1 glycosylation 976:988 pcdh O-Man glycosylation 965:988 pcdh O-Man glycosylation 965:988 KO of all four TMTC genes in HEK293 cells resulted in specific loss of cdh and pcdh O-Man glycosylation, whereas combined KO of TMTC1 and TMTC3 resulted in selective loss of O-Man glycans on specific β-strands of EC domains, suggesting that each isoenzyme serves a different function. 28973932 5 42 theme factor 1256:1261 arg1 receptor 1263:1270 hepatocyte growth factor receptor 1238:1270 hepatocyte growth factor receptor 1238:1270 In addition, O-Man glycosylation of IPT/TIG domains of plexins and hepatocyte growth factor receptor was not affected in TMTC KO cells, suggesting the existence of yet another O-Man glycosylation machinery. 28973932 2 43 theme evolutionary 499:510 arg1 enzymes 534:540 the evolutionary conserved POMT1/POMT2 enzymes 495:540 the evolutionary conserved POMT1/POMT2 enzymes that initiate O-Man glycosylation on α-DG 495:582 These O-Man glycans do not appear to be elongated like O-Man glycans found on α-dystroglycan (α-DG), and we recently demonstrated that initiation of cdh/protocadherin (pcdh) O-Man glycosylation is not dependent on the evolutionary conserved POMT1/POMT2 enzymes that initiate O-Man glycosylation on α-DG. 28973932 3 44 theme dissection 621:630 arg1 strategy 632:639 a CRISPR/Cas9 genetic dissection strategy 599:639 a CRISPR/Cas9 genetic dissection strategy combined with sensitive and quantitative O-Man glycoproteomics 599:702 Here, we used a CRISPR/Cas9 genetic dissection strategy combined with sensitive and quantitative O-Man glycoproteomics to identify a homologous family of four putative protein O-mannosyltransferases encoded by the TMTC1-4 genes, which were found to be imperative for cdh and pcdh O-Man glycosylation. 28973932 4 45 theme genes 906:910 arg1 KO 886:887 KO 886:887 KO of all four TMTC genes in HEK293 cells 886:926 KO of all four TMTC genes in HEK293 cells resulted in specific loss of cdh and pcdh O-Man glycosylation, whereas combined KO of TMTC1 and TMTC3 resulted in selective loss of O-Man glycans on specific β-strands of EC domains, suggesting that each isoenzyme serves a different function. 28973932 4 46 theme glycans 1066:1072 arg1 loss 1052:1055 selective loss 1042:1055 selective loss of O-Man glycans on specific β-strands of EC domains 1042:1108 KO of all four TMTC genes in HEK293 cells resulted in specific loss of cdh and pcdh O-Man glycosylation, whereas combined KO of TMTC1 and TMTC3 resulted in selective loss of O-Man glycans on specific β-strands of EC domains, suggesting that each isoenzyme serves a different function. 28973932 2 47 gly glycosylation 562:574 arg1 α-DG 579:582 α-DG 579:582 α-DG 579:582 These O-Man glycans do not appear to be elongated like O-Man glycans found on α-dystroglycan (α-DG), and we recently demonstrated that initiation of cdh/protocadherin (pcdh) O-Man glycosylation is not dependent on the evolutionary conserved POMT1/POMT2 enzymes that initiate O-Man glycosylation on α-DG. 28973932 2 48 theme cdh/protocadherin 430:446 arg1 glycosylation 461:473 cdh/protocadherin (pcdh) O-Man glycosylation 430:473 cdh/protocadherin (pcdh) O-Man glycosylation 430:473 These O-Man glycans do not appear to be elongated like O-Man glycans found on α-dystroglycan (α-DG), and we recently demonstrated that initiation of cdh/protocadherin (pcdh) O-Man glycosylation is not dependent on the evolutionary conserved POMT1/POMT2 enzymes that initiate O-Man glycosylation on α-DG. 28973932 0 49 theme pathway 32:38 arg1 Discovery 0:8 Discovery 0:8 Discovery of an O-mannosylation pathway 0:38 Discovery of an O-mannosylation pathway selectively serving cadherins and protocadherins. 28973932 4 50 theme TMTC1 1014:1018 arg1 KO 1008:1009 combined KO 999:1009 combined KO of TMTC1 and TMTC3 999:1028 KO of all four TMTC genes in HEK293 cells resulted in specific loss of cdh and pcdh O-Man glycosylation, whereas combined KO of TMTC1 and TMTC3 resulted in selective loss of O-Man glycans on specific β-strands of EC domains, suggesting that each isoenzyme serves a different function. 28973932 6 51 theme cobblestone 1555:1565 arg1 lissencephaly 1567:1579 cobblestone lissencephaly 1555:1579 cobblestone lissencephaly caused by deficiency in TMTC3 1555:1609 Our study demonstrates that regulation of O-mannosylation in higher eukaryotes is more complex than envisioned, and the discovery of the functions of TMTCs provide insight into cobblestone lissencephaly caused by deficiency in TMTC3. 28973932 1 52 theme localized 208:216 arg1 sites 202:206 highly conserved sites 185:206 highly conserved sites localized to specific β-strands of their extracellular cdh (EC) domains 185:278 The cadherin (cdh) superfamily of adhesion molecules carry O-linked mannose (O-Man) glycans at highly conserved sites localized to specific β-strands of their extracellular cdh (EC) domains. 28973932 4 53 theme glycosylation 976:988 arg1 loss 949:952 specific loss 940:952 specific loss of cdh and pcdh O-Man glycosylation 940:988 KO of all four TMTC genes in HEK293 cells resulted in specific loss of cdh and pcdh O-Man glycosylation, whereas combined KO of TMTC1 and TMTC3 resulted in selective loss of O-Man glycans on specific β-strands of EC domains, suggesting that each isoenzyme serves a different function. 28973932 2 54 theme O-Man 556:560 arg1 glycosylation 562:574 O-Man glycosylation 556:574 O-Man glycosylation 556:574 These O-Man glycans do not appear to be elongated like O-Man glycans found on α-dystroglycan (α-DG), and we recently demonstrated that initiation of cdh/protocadherin (pcdh) O-Man glycosylation is not dependent on the evolutionary conserved POMT1/POMT2 enzymes that initiate O-Man glycosylation on α-DG. 28973932 3 55 theme CRISPR/Cas9 601:611 arg1 strategy 632:639 a CRISPR/Cas9 genetic dissection strategy 599:639 a CRISPR/Cas9 genetic dissection strategy combined with sensitive and quantitative O-Man glycoproteomics 599:702 Here, we used a CRISPR/Cas9 genetic dissection strategy combined with sensitive and quantitative O-Man glycoproteomics to identify a homologous family of four putative protein O-mannosyltransferases encoded by the TMTC1-4 genes, which were found to be imperative for cdh and pcdh O-Man glycosylation. 28973932 4 56 from loss 1052:1055 arg1 β-strands 1086:1094 specific β-strands 1077:1094 specific β-strands of EC domains 1077:1108 KO of all four TMTC genes in HEK293 cells resulted in specific loss of cdh and pcdh O-Man glycosylation, whereas combined KO of TMTC1 and TMTC3 resulted in selective loss of O-Man glycans on specific β-strands of EC domains, suggesting that each isoenzyme serves a different function. 28973932 1 57 link O-linked 149:156 arg1 glycans 174:180 O-linked mannose (O-Man) glycans 149:180 O-linked mannose (O-Man) glycans 149:180 The cadherin (cdh) superfamily of adhesion molecules carry O-linked mannose (O-Man) glycans at highly conserved sites localized to specific β-strands of their extracellular cdh (EC) domains. 28973932 3 58 theme protein 753:759 arg1 O-mannosyltransferases 761:782 four putative protein O-mannosyltransferases 739:782 four putative protein O-mannosyltransferases encoded by the TMTC1-4 genes, which were found to be imperative for cdh and pcdh O-Man glycosylation 739:883 Here, we used a CRISPR/Cas9 genetic dissection strategy combined with sensitive and quantitative O-Man glycoproteomics to identify a homologous family of four putative protein O-mannosyltransferases encoded by the TMTC1-4 genes, which were found to be imperative for cdh and pcdh O-Man glycosylation. 28973932 4 59 theme TMTC 901:904 arg1 genes 906:910 all four TMTC genes 892:910 all four TMTC genes 892:910 KO of all four TMTC genes in HEK293 cells resulted in specific loss of cdh and pcdh O-Man glycosylation, whereas combined KO of TMTC1 and TMTC3 resulted in selective loss of O-Man glycans on specific β-strands of EC domains, suggesting that each isoenzyme serves a different function. 28973932 5 60 theme growth 1249:1254 arg1 factor 1256:1261 hepatocyte growth factor 1238:1261 hepatocyte growth factor receptor 1238:1270 In addition, O-Man glycosylation of IPT/TIG domains of plexins and hepatocyte growth factor receptor was not affected in TMTC KO cells, suggesting the existence of yet another O-Man glycosylation machinery. 28973932 1 61 theme O-linked 149:156 arg1 glycans 174:180 O-linked mannose (O-Man) glycans 149:180 O-linked mannose (O-Man) glycans 149:180 The cadherin (cdh) superfamily of adhesion molecules carry O-linked mannose (O-Man) glycans at highly conserved sites localized to specific β-strands of their extracellular cdh (EC) domains. 28973932 5 62 theme plexins 1226:1232 arg1 domains 1215:1221 IPT/TIG domains 1207:1221 IPT/TIG domains of plexins and hepatocyte growth factor receptor 1207:1270 In addition, O-Man glycosylation of IPT/TIG domains of plexins and hepatocyte growth factor receptor was not affected in TMTC KO cells, suggesting the existence of yet another O-Man glycosylation machinery. 28973932 5 62 theme plexins 1226:1232 arg1 receptor 1263:1270 hepatocyte growth factor receptor 1238:1270 hepatocyte growth factor receptor 1238:1270 In addition, O-Man glycosylation of IPT/TIG domains of plexins and hepatocyte growth factor receptor was not affected in TMTC KO cells, suggesting the existence of yet another O-Man glycosylation machinery. 28973932 5 62 theme plexins 1226:1232 arg1 plexins 1226:1232 plexins 1226:1232 plexins 1226:1232 In addition, O-Man glycosylation of IPT/TIG domains of plexins and hepatocyte growth factor receptor was not affected in TMTC KO cells, suggesting the existence of yet another O-Man glycosylation machinery. 28973932 3 63 theme O-mannosyltransferases 761:782 arg1 family 729:734 a homologous family 716:734 a homologous family of four putative protein O-mannosyltransferases encoded by the TMTC1-4 genes, which were found to be imperative for cdh and pcdh O-Man glycosylation 716:883 Here, we used a CRISPR/Cas9 genetic dissection strategy combined with sensitive and quantitative O-Man glycoproteomics to identify a homologous family of four putative protein O-mannosyltransferases encoded by the TMTC1-4 genes, which were found to be imperative for cdh and pcdh O-Man glycosylation. 28973932 3 64 theme sensitive 655:663 arg1 glycoproteomics 688:702 sensitive and quantitative O-Man glycoproteomics 655:702 sensitive and quantitative O-Man glycoproteomics 655:702 Here, we used a CRISPR/Cas9 genetic dissection strategy combined with sensitive and quantitative O-Man glycoproteomics to identify a homologous family of four putative protein O-mannosyltransferases encoded by the TMTC1-4 genes, which were found to be imperative for cdh and pcdh O-Man glycosylation. 28973932 1 65 theme adhesion 124:131 arg1 molecules 133:141 adhesion molecules 124:141 adhesion molecules 124:141 The cadherin (cdh) superfamily of adhesion molecules carry O-linked mannose (O-Man) glycans at highly conserved sites localized to specific β-strands of their extracellular cdh (EC) domains. 28973932 2 66 theme O-Man 287:291 arg1 glycans 293:299 These O-Man glycans 281:299 These O-Man glycans 281:299 These O-Man glycans do not appear to be elongated like O-Man glycans found on α-dystroglycan (α-DG), and we recently demonstrated that initiation of cdh/protocadherin (pcdh) O-Man glycosylation is not dependent on the evolutionary conserved POMT1/POMT2 enzymes that initiate O-Man glycosylation on α-DG. 28973932 4 67 from KO 886:887 arg1 cells 922:926 HEK293 cells 915:926 HEK293 cells 915:926 KO of all four TMTC genes in HEK293 cells resulted in specific loss of cdh and pcdh O-Man glycosylation, whereas combined KO of TMTC1 and TMTC3 resulted in selective loss of O-Man glycans on specific β-strands of EC domains, suggesting that each isoenzyme serves a different function. 28973932 6 68 from regulation 1406:1415 arg1 eukaryotes 1446:1455 higher eukaryotes 1439:1455 higher eukaryotes 1439:1455 Our study demonstrates that regulation of O-mannosylation in higher eukaryotes is more complex than envisioned, and the discovery of the functions of TMTCs provide insight into cobblestone lissencephaly caused by deficiency in TMTC3. 28973932 6 69 theme TMTCs 1528:1532 arg1 functions 1515:1523 the functions 1511:1523 the functions of TMTCs 1511:1532 Our study demonstrates that regulation of O-mannosylation in higher eukaryotes is more complex than envisioned, and the discovery of the functions of TMTCs provide insight into cobblestone lissencephaly caused by deficiency in TMTC3. 28973932 1 70 theme molecules 133:141 arg1 superfamily 109:119 The cadherin (cdh) superfamily 90:119 The cadherin (cdh) superfamily of adhesion molecules 90:141 The cadherin (cdh) superfamily of adhesion molecules carry O-linked mannose (O-Man) glycans at highly conserved sites localized to specific β-strands of their extracellular cdh (EC) domains. 28973932 5 71 theme hepatocyte 1238:1247 arg1 factor 1256:1261 hepatocyte growth factor 1238:1261 hepatocyte growth factor receptor 1238:1270 In addition, O-Man glycosylation of IPT/TIG domains of plexins and hepatocyte growth factor receptor was not affected in TMTC KO cells, suggesting the existence of yet another O-Man glycosylation machinery. 28973932 1 72 theme specific 221:228 arg1 β-strands 230:238 specific β-strands 221:238 specific β-strands of their extracellular cdh (EC) domains 221:278 The cadherin (cdh) superfamily of adhesion molecules carry O-linked mannose (O-Man) glycans at highly conserved sites localized to specific β-strands of their extracellular cdh (EC) domains. 28973932 2 73 theme glycosylation 461:473 arg1 initiation 416:425 initiation 416:425 initiation of cdh/protocadherin (pcdh) O-Man glycosylation 416:473 These O-Man glycans do not appear to be elongated like O-Man glycans found on α-dystroglycan (α-DG), and we recently demonstrated that initiation of cdh/protocadherin (pcdh) O-Man glycosylation is not dependent on the evolutionary conserved POMT1/POMT2 enzymes that initiate O-Man glycosylation on α-DG. 28973932 4 74 dep resulted 928:935 arg1 whereas 991:997 whereas 991:997 whereas 991:997 KO of all four TMTC genes in HEK293 cells resulted in specific loss of cdh and pcdh O-Man glycosylation, whereas combined KO of TMTC1 and TMTC3 resulted in selective loss of O-Man glycans on specific β-strands of EC domains, suggesting that each isoenzyme serves a different function. 28973932 4 75 theme domains 1102:1108 arg1 β-strands 1086:1094 specific β-strands 1077:1094 specific β-strands of EC domains 1077:1108 KO of all four TMTC genes in HEK293 cells resulted in specific loss of cdh and pcdh O-Man glycosylation, whereas combined KO of TMTC1 and TMTC3 resulted in selective loss of O-Man glycans on specific β-strands of EC domains, suggesting that each isoenzyme serves a different function. 28973932 4 76 theme selective 1042:1050 arg1 loss 1052:1055 selective loss 1042:1055 selective loss of O-Man glycans on specific β-strands of EC domains 1042:1108 KO of all four TMTC genes in HEK293 cells resulted in specific loss of cdh and pcdh O-Man glycosylation, whereas combined KO of TMTC1 and TMTC3 resulted in selective loss of O-Man glycans on specific β-strands of EC domains, suggesting that each isoenzyme serves a different function. 28973932 5 77 theme O-Man 1184:1188 arg1 glycosylation 1190:1202 O-Man glycosylation 1184:1202 O-Man glycosylation of IPT/TIG domains of plexins and hepatocyte growth factor receptor 1184:1270 In addition, O-Man glycosylation of IPT/TIG domains of plexins and hepatocyte growth factor receptor was not affected in TMTC KO cells, suggesting the existence of yet another O-Man glycosylation machinery. 28973932 2 78 theme O-Man 455:459 arg1 glycosylation 461:473 cdh/protocadherin (pcdh) O-Man glycosylation 430:473 cdh/protocadherin (pcdh) O-Man glycosylation 430:473 These O-Man glycans do not appear to be elongated like O-Man glycans found on α-dystroglycan (α-DG), and we recently demonstrated that initiation of cdh/protocadherin (pcdh) O-Man glycosylation is not dependent on the evolutionary conserved POMT1/POMT2 enzymes that initiate O-Man glycosylation on α-DG. 28973932 3 79 theme O-Man 682:686 arg1 glycoproteomics 688:702 sensitive and quantitative O-Man glycoproteomics 655:702 sensitive and quantitative O-Man glycoproteomics 655:702 Here, we used a CRISPR/Cas9 genetic dissection strategy combined with sensitive and quantitative O-Man glycoproteomics to identify a homologous family of four putative protein O-mannosyltransferases encoded by the TMTC1-4 genes, which were found to be imperative for cdh and pcdh O-Man glycosylation. 28973932 6 80 from deficiency 1591:1600 arg1 TMTC3 1605:1609 TMTC3 1605:1609 TMTC3 1605:1609 Our study demonstrates that regulation of O-mannosylation in higher eukaryotes is more complex than envisioned, and the discovery of the functions of TMTCs provide insight into cobblestone lissencephaly caused by deficiency in TMTC3. 28973932 6 81 theme functions 1515:1523 arg1 discovery 1498:1506 the discovery 1494:1506 the discovery of the functions of TMTCs 1494:1532 Our study demonstrates that regulation of O-mannosylation in higher eukaryotes is more complex than envisioned, and the discovery of the functions of TMTCs provide insight into cobblestone lissencephaly caused by deficiency in TMTC3. 28973932 2 82 theme O-Man 336:340 arg1 glycans 342:348 O-Man glycans 336:348 O-Man glycans 336:348 These O-Man glycans do not appear to be elongated like O-Man glycans found on α-dystroglycan (α-DG), and we recently demonstrated that initiation of cdh/protocadherin (pcdh) O-Man glycosylation is not dependent on the evolutionary conserved POMT1/POMT2 enzymes that initiate O-Man glycosylation on α-DG. 28973932 3 83 theme O-Man 865:869 arg1 glycosylation 871:883 O-Man glycosylation 865:883 O-Man glycosylation 865:883 Here, we used a CRISPR/Cas9 genetic dissection strategy combined with sensitive and quantitative O-Man glycoproteomics to identify a homologous family of four putative protein O-mannosyltransferases encoded by the TMTC1-4 genes, which were found to be imperative for cdh and pcdh O-Man glycosylation. 27056667 6 0 theme catalytic 976:984 arg1 residues 993:1000 key catalytic domain residues 972:1000 key catalytic domain residues 972:1000 In contrast, key catalytic domain residues and even a UDP-GlcNAc oxygen important for Ser/Thr glycosylation are irrelevant for proteolysis. 27056667 1 1 theme O-linked-GlcNAc 170:184 arg1 OGT 199:201 OGT 199:201 OGT 199:201 In complex with the cosubstrate UDP-N-acetylglucosamine (UDP-GlcNAc),O-linked-GlcNAc transferase (OGT) catalyzes Ser/ThrO-GlcNAcylation of many cellular proteins and proteolysis of the transcriptional coregulator HCF-1. 27056667 1 1 theme O-linked-GlcNAc 170:184 arg1 transferase 186:196 O-linked-GlcNAc transferase 170:196 O-linked-GlcNAc transferase (OGT) 170:202 In complex with the cosubstrate UDP-N-acetylglucosamine (UDP-GlcNAc),O-linked-GlcNAc transferase (OGT) catalyzes Ser/ThrO-GlcNAcylation of many cellular proteins and proteolysis of the transcriptional coregulator HCF-1. 27056667 6 2 theme key 972:974 arg1 residues 993:1000 key catalytic domain residues 972:1000 key catalytic domain residues 972:1000 In contrast, key catalytic domain residues and even a UDP-GlcNAc oxygen important for Ser/Thr glycosylation are irrelevant for proteolysis. 27056667 8 3 theme OGT-mediated 1247:1258 arg1 proteolysis 1266:1276 OGT-mediated HCF-1 proteolysis 1247:1276 OGT-mediated HCF-1 proteolysis 1247:1276 Curiously, whereas OGT-mediated HCF-1 proteolysis is limited to vertebrate species, invertebrate OGTs can cleave human HCF-1. 27056667 2 4 theme active 397:402 arg1 site 404:407 the same active site 388:407 the same active site 388:407 Such a dual glycosyltransferase-protease activity, which occurs in the same active site, is unprecedented and integrates both reversible and irreversible forms of protein post-translational modification within one enzyme. 27056667 1 5 theme transcriptional 286:300 arg1 HCF-1 314:318 the transcriptional coregulator HCF-1 282:318 the transcriptional coregulator HCF-1 282:318 In complex with the cosubstrate UDP-N-acetylglucosamine (UDP-GlcNAc),O-linked-GlcNAc transferase (OGT) catalyzes Ser/ThrO-GlcNAcylation of many cellular proteins and proteolysis of the transcriptional coregulator HCF-1. 27056667 2 6 theme dual 328:331 arg1 activity 362:369 Such a dual glycosyltransferase-protease activity 321:369 Such a dual glycosyltransferase-protease activity 321:369 Such a dual glycosyltransferase-protease activity, which occurs in the same active site, is unprecedented and integrates both reversible and irreversible forms of protein post-translational modification within one enzyme. 27056667 2 6 theme dual 328:331 arg1 unprecedented 413:425 unprecedented 413:425 unprecedented 413:425 Such a dual glycosyltransferase-protease activity, which occurs in the same active site, is unprecedented and integrates both reversible and irreversible forms of protein post-translational modification within one enzyme. 27056667 1 7 theme coregulator 302:312 arg1 HCF-1 314:318 the transcriptional coregulator HCF-1 282:318 the transcriptional coregulator HCF-1 282:318 In complex with the cosubstrate UDP-N-acetylglucosamine (UDP-GlcNAc),O-linked-GlcNAc transferase (OGT) catalyzes Ser/ThrO-GlcNAcylation of many cellular proteins and proteolysis of the transcriptional coregulator HCF-1. 27056667 6 8 theme Ser/Thr 1045:1051 arg1 glycosylation 1053:1065 Ser/Thr glycosylation 1045:1065 Ser/Thr glycosylation 1045:1065 In contrast, key catalytic domain residues and even a UDP-GlcNAc oxygen important for Ser/Thr glycosylation are irrelevant for proteolysis. 27056667 3 9 theme same 573:576 arg1 site 585:588 the same active site 569:588 the same active site 569:588 Although occurring within the same active site, we show here that glycosylation and proteolysis occur through separable mechanisms. 27056667 1 10 theme HCF-1 314:318 arg1 proteolysis 267:277 proteolysis 267:277 proteolysis of the transcriptional coregulator HCF-1 267:318 In complex with the cosubstrate UDP-N-acetylglucosamine (UDP-GlcNAc),O-linked-GlcNAc transferase (OGT) catalyzes Ser/ThrO-GlcNAcylation of many cellular proteins and proteolysis of the transcriptional coregulator HCF-1. 27056667 1 10 theme HCF-1 314:318 arg1 Ser/ThrO-GlcNAcylation 214:235 Ser/ThrO-GlcNAcylation 214:235 Ser/ThrO-GlcNAcylation of many cellular proteins 214:261 In complex with the cosubstrate UDP-N-acetylglucosamine (UDP-GlcNAc),O-linked-GlcNAc transferase (OGT) catalyzes Ser/ThrO-GlcNAcylation of many cellular proteins and proteolysis of the transcriptional coregulator HCF-1. 27056667 6 11 from contrast 962:969 arg1 oxygen 1024:1029 even a UDP-GlcNAc oxygen 1006:1029 even a UDP-GlcNAc oxygen 1006:1029 In contrast, key catalytic domain residues and even a UDP-GlcNAc oxygen important for Ser/Thr glycosylation are irrelevant for proteolysis. 27056667 6 11 from contrast 962:969 arg1 irrelevant 1071:1080 irrelevant 1071:1080 irrelevant 1071:1080 In contrast, key catalytic domain residues and even a UDP-GlcNAc oxygen important for Ser/Thr glycosylation are irrelevant for proteolysis. 27056667 1 12 theme cosubstrate 121:131 arg1 UDP-GlcNAc 158:167 UDP-GlcNAc 158:167 UDP-GlcNAc 158:167 In complex with the cosubstrate UDP-N-acetylglucosamine (UDP-GlcNAc),O-linked-GlcNAc transferase (OGT) catalyzes Ser/ThrO-GlcNAcylation of many cellular proteins and proteolysis of the transcriptional coregulator HCF-1. 27056667 1 12 theme cosubstrate 121:131 arg1 UDP-N-acetylglucosamine 133:155 the cosubstrate UDP-N-acetylglucosamine 117:155 the cosubstrate UDP-N-acetylglucosamine (UDP-GlcNAc) 117:168 In complex with the cosubstrate UDP-N-acetylglucosamine (UDP-GlcNAc),O-linked-GlcNAc transferase (OGT) catalyzes Ser/ThrO-GlcNAcylation of many cellular proteins and proteolysis of the transcriptional coregulator HCF-1. 27056667 4 13 theme catalytic 726:734 arg1 domains 736:742 catalytic domains 726:742 catalytic domains 726:742 OGT consists of tetratricopeptide repeat (TPR) and catalytic domains, which, together with UDP-GlcNAc, are required for both glycosylation and proteolysis. 27056667 5 14 theme domain 860:865 arg1 critical 903:910 critical 903:910 critical 903:910 Nevertheless, a specific TPR domain contact with the HCF-1 substrate is critical for proteolysis but not Ser/Thr glycosylation. 27056667 5 14 theme domain 860:865 arg1 contact 867:873 a specific TPR domain contact 845:873 a specific TPR domain contact with the HCF-1 substrate 845:898 Nevertheless, a specific TPR domain contact with the HCF-1 substrate is critical for proteolysis but not Ser/Thr glycosylation. 27056667 9 15 theme HCF-1 1394:1398 arg1 proteolysis 1400:1410 HCF-1 proteolysis 1394:1410 HCF-1 proteolysis 1394:1410 We present a model for the evolution of HCF-1 proteolysis by OGT. 27056667 8 16 theme HCF-1 1260:1264 arg1 proteolysis 1266:1276 OGT-mediated HCF-1 proteolysis 1247:1276 OGT-mediated HCF-1 proteolysis 1247:1276 Curiously, whereas OGT-mediated HCF-1 proteolysis is limited to vertebrate species, invertebrate OGTs can cleave human HCF-1. 27056667 2 17 theme modification 511:522 arg1 forms 475:479 both reversible and irreversible forms 442:479 both reversible and irreversible forms of protein post-translational modification within one enzyme 442:540 Such a dual glycosyltransferase-protease activity, which occurs in the same active site, is unprecedented and integrates both reversible and irreversible forms of protein post-translational modification within one enzyme. 27056667 9 18 theme proteolysis 1400:1410 arg1 evolution 1381:1389 the evolution 1377:1389 the evolution of HCF-1 proteolysis by OGT 1377:1417 We present a model for the evolution of HCF-1 proteolysis by OGT. 27056667 6 19 from irrelevant 1071:1080 arg1 contrast 962:969 contrast 962:969 contrast 962:969 In contrast, key catalytic domain residues and even a UDP-GlcNAc oxygen important for Ser/Thr glycosylation are irrelevant for proteolysis. 27056667 8 20 theme human 1341:1345 arg1 HCF-1 1347:1351 human HCF-1 1341:1351 human HCF-1 1341:1351 Curiously, whereas OGT-mediated HCF-1 proteolysis is limited to vertebrate species, invertebrate OGTs can cleave human HCF-1. 27056667 2 21 theme post-translational 492:509 arg1 modification 511:522 protein post-translational modification 484:522 protein post-translational modification within one enzyme 484:540 Such a dual glycosyltransferase-protease activity, which occurs in the same active site, is unprecedented and integrates both reversible and irreversible forms of protein post-translational modification within one enzyme. 27056667 0 22 dep complexes 90:98 arg1 Proteolysis 0:10 Proteolysis 0:10 Proteolysis of HCF-1 by Ser/Thr glycosylation-incompetent O-GlcNAc transferase 0:77 Proteolysis of HCF-1 by Ser/Thr glycosylation-incompetent O-GlcNAc transferase:UDP-GlcNAc complexes. 27056667 5 23 theme Ser/Thr 936:942 arg1 glycosylation 944:956 Ser/Thr glycosylation 936:956 proteolysis but not Ser/Thr glycosylation 916:956 Nevertheless, a specific TPR domain contact with the HCF-1 substrate is critical for proteolysis but not Ser/Thr glycosylation. 27056667 2 24 theme protein 484:490 arg1 modification 511:522 protein post-translational modification 484:522 protein post-translational modification within one enzyme 484:540 Such a dual glycosyltransferase-protease activity, which occurs in the same active site, is unprecedented and integrates both reversible and irreversible forms of protein post-translational modification within one enzyme. 27056667 6 25 theme important 1031:1039 arg1 residues 993:1000 key catalytic domain residues 972:1000 key catalytic domain residues 972:1000 In contrast, key catalytic domain residues and even a UDP-GlcNAc oxygen important for Ser/Thr glycosylation are irrelevant for proteolysis. 27056667 5 26 with contact 867:873 arg1 substrate 890:898 the HCF-1 substrate 880:898 the HCF-1 substrate 880:898 Nevertheless, a specific TPR domain contact with the HCF-1 substrate is critical for proteolysis but not Ser/Thr glycosylation. 27056667 1 27 with complex 104:110 arg1 UDP-GlcNAc 158:167 UDP-GlcNAc 158:167 UDP-GlcNAc 158:167 In complex with the cosubstrate UDP-N-acetylglucosamine (UDP-GlcNAc),O-linked-GlcNAc transferase (OGT) catalyzes Ser/ThrO-GlcNAcylation of many cellular proteins and proteolysis of the transcriptional coregulator HCF-1. 27056667 1 27 with complex 104:110 arg1 UDP-N-acetylglucosamine 133:155 the cosubstrate UDP-N-acetylglucosamine 117:155 the cosubstrate UDP-N-acetylglucosamine (UDP-GlcNAc) 117:168 In complex with the cosubstrate UDP-N-acetylglucosamine (UDP-GlcNAc),O-linked-GlcNAc transferase (OGT) catalyzes Ser/ThrO-GlcNAcylation of many cellular proteins and proteolysis of the transcriptional coregulator HCF-1. 27056667 7 28 theme single-activity 1159:1173 arg1 enzymes 1175:1181 essentially single-activity enzymes 1147:1181 essentially single-activity enzymes 1147:1181 Thus, from a dual glycosyltransferase-protease, essentially single-activity enzymes can be engineered both in vitro and in vivo. 27056667 2 29 theme glycosyltransferase-protease 333:360 arg1 activity 362:369 Such a dual glycosyltransferase-protease activity 321:369 Such a dual glycosyltransferase-protease activity 321:369 Such a dual glycosyltransferase-protease activity, which occurs in the same active site, is unprecedented and integrates both reversible and irreversible forms of protein post-translational modification within one enzyme. 27056667 2 29 theme glycosyltransferase-protease 333:360 arg1 unprecedented 413:425 unprecedented 413:425 unprecedented 413:425 Such a dual glycosyltransferase-protease activity, which occurs in the same active site, is unprecedented and integrates both reversible and irreversible forms of protein post-translational modification within one enzyme. 27056667 2 30 theme irreversible 462:473 arg1 forms 475:479 both reversible and irreversible forms 442:479 both reversible and irreversible forms of protein post-translational modification within one enzyme 442:540 Such a dual glycosyltransferase-protease activity, which occurs in the same active site, is unprecedented and integrates both reversible and irreversible forms of protein post-translational modification within one enzyme. 27056667 0 31 theme glycosylation-incompetent 32:56 arg1 transferase 67:77 Ser/Thr glycosylation-incompetent O-GlcNAc transferase 24:77 Ser/Thr glycosylation-incompetent O-GlcNAc transferase 24:77 Proteolysis of HCF-1 by Ser/Thr glycosylation-incompetent O-GlcNAc transferase:UDP-GlcNAc complexes. 27056667 6 32 theme UDP-GlcNAc 1013:1022 arg1 oxygen 1024:1029 even a UDP-GlcNAc oxygen 1006:1029 even a UDP-GlcNAc oxygen 1006:1029 In contrast, key catalytic domain residues and even a UDP-GlcNAc oxygen important for Ser/Thr glycosylation are irrelevant for proteolysis. 27056667 6 32 theme UDP-GlcNAc 1013:1022 arg1 irrelevant 1071:1080 irrelevant 1071:1080 irrelevant 1071:1080 In contrast, key catalytic domain residues and even a UDP-GlcNAc oxygen important for Ser/Thr glycosylation are irrelevant for proteolysis. 27056667 1 33 theme many 240:243 arg1 proteins 254:261 many cellular proteins 240:261 many cellular proteins 240:261 In complex with the cosubstrate UDP-N-acetylglucosamine (UDP-GlcNAc),O-linked-GlcNAc transferase (OGT) catalyzes Ser/ThrO-GlcNAcylation of many cellular proteins and proteolysis of the transcriptional coregulator HCF-1. 27056667 0 34 theme Ser/Thr 24:30 arg1 transferase 67:77 Ser/Thr glycosylation-incompetent O-GlcNAc transferase 24:77 Ser/Thr glycosylation-incompetent O-GlcNAc transferase 24:77 Proteolysis of HCF-1 by Ser/Thr glycosylation-incompetent O-GlcNAc transferase:UDP-GlcNAc complexes. 27056667 5 35 theme specific 847:854 arg1 critical 903:910 critical 903:910 critical 903:910 Nevertheless, a specific TPR domain contact with the HCF-1 substrate is critical for proteolysis but not Ser/Thr glycosylation. 27056667 5 35 theme specific 847:854 arg1 contact 867:873 a specific TPR domain contact 845:873 a specific TPR domain contact with the HCF-1 substrate 845:898 Nevertheless, a specific TPR domain contact with the HCF-1 substrate is critical for proteolysis but not Ser/Thr glycosylation. 27056667 1 36 theme cellular 245:252 arg1 proteins 254:261 many cellular proteins 240:261 many cellular proteins 240:261 In complex with the cosubstrate UDP-N-acetylglucosamine (UDP-GlcNAc),O-linked-GlcNAc transferase (OGT) catalyzes Ser/ThrO-GlcNAcylation of many cellular proteins and proteolysis of the transcriptional coregulator HCF-1. 27056667 5 37 theme TPR 856:858 arg1 critical 903:910 critical 903:910 critical 903:910 Nevertheless, a specific TPR domain contact with the HCF-1 substrate is critical for proteolysis but not Ser/Thr glycosylation. 27056667 5 37 theme TPR 856:858 arg1 contact 867:873 a specific TPR domain contact 845:873 a specific TPR domain contact with the HCF-1 substrate 845:898 Nevertheless, a specific TPR domain contact with the HCF-1 substrate is critical for proteolysis but not Ser/Thr glycosylation. 27056667 8 38 theme vertebrate 1292:1301 arg1 species 1303:1309 vertebrate species 1292:1309 vertebrate species 1292:1309 Curiously, whereas OGT-mediated HCF-1 proteolysis is limited to vertebrate species, invertebrate OGTs can cleave human HCF-1. 27056667 2 39 theme same 392:395 arg1 site 404:407 the same active site 388:407 the same active site 388:407 Such a dual glycosyltransferase-protease activity, which occurs in the same active site, is unprecedented and integrates both reversible and irreversible forms of protein post-translational modification within one enzyme. 27056667 0 40 theme O-GlcNAc 58:65 arg1 transferase 67:77 Ser/Thr glycosylation-incompetent O-GlcNAc transferase 24:77 Ser/Thr glycosylation-incompetent O-GlcNAc transferase 24:77 Proteolysis of HCF-1 by Ser/Thr glycosylation-incompetent O-GlcNAc transferase:UDP-GlcNAc complexes. 27056667 7 41 theme dual 1112:1115 arg1 glycosyltransferase-protease 1117:1144 a dual glycosyltransferase-protease 1110:1144 a dual glycosyltransferase-protease 1110:1144 Thus, from a dual glycosyltransferase-protease, essentially single-activity enzymes can be engineered both in vitro and in vivo. 27056667 3 42 theme separable 653:661 arg1 mechanisms 663:672 separable mechanisms 653:672 separable mechanisms 653:672 Although occurring within the same active site, we show here that glycosylation and proteolysis occur through separable mechanisms. 27056667 3 43 theme active 578:583 arg1 site 585:588 the same active site 569:588 the same active site 569:588 Although occurring within the same active site, we show here that glycosylation and proteolysis occur through separable mechanisms. 27056667 1 44 theme proteins 254:261 arg1 proteolysis 267:277 proteolysis 267:277 proteolysis of the transcriptional coregulator HCF-1 267:318 In complex with the cosubstrate UDP-N-acetylglucosamine (UDP-GlcNAc),O-linked-GlcNAc transferase (OGT) catalyzes Ser/ThrO-GlcNAcylation of many cellular proteins and proteolysis of the transcriptional coregulator HCF-1. 27056667 1 44 theme proteins 254:261 arg1 Ser/ThrO-GlcNAcylation 214:235 Ser/ThrO-GlcNAcylation 214:235 Ser/ThrO-GlcNAcylation of many cellular proteins 214:261 In complex with the cosubstrate UDP-N-acetylglucosamine (UDP-GlcNAc),O-linked-GlcNAc transferase (OGT) catalyzes Ser/ThrO-GlcNAcylation of many cellular proteins and proteolysis of the transcriptional coregulator HCF-1. 27056667 5 45 theme HCF-1 884:888 arg1 substrate 890:898 the HCF-1 substrate 880:898 the HCF-1 substrate 880:898 Nevertheless, a specific TPR domain contact with the HCF-1 substrate is critical for proteolysis but not Ser/Thr glycosylation. 27056667 0 46 theme UDP-GlcNAc 79:88 arg1 complexes 90:98 UDP-GlcNAc complexes 79:98 UDP-GlcNAc complexes 79:98 Proteolysis of HCF-1 by Ser/Thr glycosylation-incompetent O-GlcNAc transferase:UDP-GlcNAc complexes. 27056667 2 47 theme reversible 447:456 arg1 forms 475:479 both reversible and irreversible forms 442:479 both reversible and irreversible forms of protein post-translational modification within one enzyme 442:540 Such a dual glycosyltransferase-protease activity, which occurs in the same active site, is unprecedented and integrates both reversible and irreversible forms of protein post-translational modification within one enzyme. 27056667 4 48 theme tetratricopeptide 691:707 arg1 TPR 717:719 TPR 717:719 TPR 717:719 OGT consists of tetratricopeptide repeat (TPR) and catalytic domains, which, together with UDP-GlcNAc, are required for both glycosylation and proteolysis. 27056667 4 48 theme tetratricopeptide 691:707 arg1 repeat 709:714 tetratricopeptide repeat 691:714 tetratricopeptide repeat (TPR) 691:720 OGT consists of tetratricopeptide repeat (TPR) and catalytic domains, which, together with UDP-GlcNAc, are required for both glycosylation and proteolysis. 27056667 8 49 theme invertebrate 1312:1323 arg1 OGTs 1325:1328 invertebrate OGTs 1312:1328 invertebrate OGTs 1312:1328 Curiously, whereas OGT-mediated HCF-1 proteolysis is limited to vertebrate species, invertebrate OGTs can cleave human HCF-1. 27056667 6 50 theme domain 986:991 arg1 residues 993:1000 key catalytic domain residues 972:1000 key catalytic domain residues 972:1000 In contrast, key catalytic domain residues and even a UDP-GlcNAc oxygen important for Ser/Thr glycosylation are irrelevant for proteolysis. 27056667 0 51 theme HCF-1 15:19 arg1 Proteolysis 0:10 Proteolysis 0:10 Proteolysis of HCF-1 by Ser/Thr glycosylation-incompetent O-GlcNAc transferase 0:77 Proteolysis of HCF-1 by Ser/Thr glycosylation-incompetent O-GlcNAc transferase:UDP-GlcNAc complexes. 29048831 3 0 theme material 715:722 arg1 property 692:699 hydrophilic property 680:699 hydrophilic property of the porous material 680:722 The specific surface area was 166 m2/g, and the water contact angle was 46.4°, exhibiting hydrophilic property of the porous material. 29048831 5 1 theme mouse 1242:1246 arg1 digest 1262:1267 100 μ g mouse liver tryptic digest 1234:1267 100 μ g mouse liver tryptic digest 1234:1267 The 19 typical N-linked glycopeptides were identified from 500 fmol tryptic digest of immunoglobulin G (IgG) from human serum by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis, meanwhile, 1919 unique glycopeptides with 1350 N-glycosylation sites from 605 different N-linked glycoproteins were identified from 100 μ g mouse liver tryptic digest by capillary liquid chromatography (cLC)-MS/MS analysis. 29048831 3 2 theme specific 594:601 arg1 area 611:614 The specific surface area 590:614 The specific surface area 590:614 The specific surface area was 166 m2/g, and the water contact angle was 46.4°, exhibiting hydrophilic property of the porous material. 29048831 3 2 theme specific 594:601 arg1 m2/g 624:627 166 m2/g 620:627 166 m2/g 620:627 The specific surface area was 166 m2/g, and the water contact angle was 46.4°, exhibiting hydrophilic property of the porous material. 29048831 5 3 theme tryptic 1254:1260 arg1 digest 1262:1267 100 μ g mouse liver tryptic digest 1234:1267 100 μ g mouse liver tryptic digest 1234:1267 The 19 typical N-linked glycopeptides were identified from 500 fmol tryptic digest of immunoglobulin G (IgG) from human serum by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis, meanwhile, 1919 unique glycopeptides with 1350 N-glycosylation sites from 605 different N-linked glycoproteins were identified from 100 μ g mouse liver tryptic digest by capillary liquid chromatography (cLC)-MS/MS analysis. 29048831 1 4 theme organic 141:147 arg1 POP 158:160 POP 158:160 POP 158:160 An acylsemicarbazide-based porous organic polymer (POP) was facilely prepared by the polymerization of benzene-1,3,5-tricarbohydrazide (BTZ) and 1,4-phenylene diisocyanate (PDI). 29048831 1 4 theme organic 141:147 arg1 polymer 149:155 An acylsemicarbazide-based porous organic polymer 107:155 An acylsemicarbazide-based porous organic polymer (POP) 107:161 An acylsemicarbazide-based porous organic polymer (POP) was facilely prepared by the polymerization of benzene-1,3,5-tricarbohydrazide (BTZ) and 1,4-phenylene diisocyanate (PDI). 29048831 5 5 gly N-glycosylation 1149:1163 arg2 sites 1165:1169 1350 N-glycosylation sites 1144:1169 1350 N-glycosylation sites 1144:1169 The 19 typical N-linked glycopeptides were identified from 500 fmol tryptic digest of immunoglobulin G (IgG) from human serum by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis, meanwhile, 1919 unique glycopeptides with 1350 N-glycosylation sites from 605 different N-linked glycoproteins were identified from 100 μ g mouse liver tryptic digest by capillary liquid chromatography (cLC)-MS/MS analysis. 29048831 5 5 gly N-glycosylation 1149:1163 arg2 1350 1144:1147 1350 1144:1147 1350 1144:1147 The 19 typical N-linked glycopeptides were identified from 500 fmol tryptic digest of immunoglobulin G (IgG) from human serum by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis, meanwhile, 1919 unique glycopeptides with 1350 N-glycosylation sites from 605 different N-linked glycoproteins were identified from 100 μ g mouse liver tryptic digest by capillary liquid chromatography (cLC)-MS/MS analysis. 29048831 2 6 theme physical 290:297 arg1 properties 299:308 The physical properties 286:308 The physical properties of as-synthesized material 286:335 The physical properties of as-synthesized material were characterized by Fourier-transform infrared spectroscopy (FT-IR), solid-state cross polarisation magic angle spinning carbon-13 nuclear magnetic resonance (CP-MAS 13C NMR), nitrogen adsorption/desorption measurement, water contact angle and so on. 29048831 5 7 theme N-linked 886:893 arg1 glycopeptides 895:907 The 19 typical N-linked glycopeptides 871:907 The 19 typical N-linked glycopeptides 871:907 The 19 typical N-linked glycopeptides were identified from 500 fmol tryptic digest of immunoglobulin G (IgG) from human serum by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis, meanwhile, 1919 unique glycopeptides with 1350 N-glycosylation sites from 605 different N-linked glycoproteins were identified from 100 μ g mouse liver tryptic digest by capillary liquid chromatography (cLC)-MS/MS analysis. 29048831 6 8 theme POP-1 1376:1380 arg1 potential 1363:1371 the great potential 1353:1371 the great potential of POP-1 for glycoproteome analysis 1353:1407 These results demonstrated the great potential of POP-1 for glycoproteome analysis. 29048831 2 9 theme material 328:335 arg1 properties 299:308 The physical properties 286:308 The physical properties of as-synthesized material 286:335 The physical properties of as-synthesized material were characterized by Fourier-transform infrared spectroscopy (FT-IR), solid-state cross polarisation magic angle spinning carbon-13 nuclear magnetic resonance (CP-MAS 13C NMR), nitrogen adsorption/desorption measurement, water contact angle and so on. 29048831 4 10 from biosamples 839:848 arg1 mode 865:868 hydrophilic mode 853:868 hydrophilic mode 853:868 Thus, POP-1 was tried to be used for glycopeptides enrichment from tryptic digest of standard protein and complex biosamples in hydrophilic mode. 29048831 5 11 theme immunoglobulin 957:970 arg1 IgG 975:977 IgG 975:977 IgG 975:977 The 19 typical N-linked glycopeptides were identified from 500 fmol tryptic digest of immunoglobulin G (IgG) from human serum by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis, meanwhile, 1919 unique glycopeptides with 1350 N-glycosylation sites from 605 different N-linked glycoproteins were identified from 100 μ g mouse liver tryptic digest by capillary liquid chromatography (cLC)-MS/MS analysis. 29048831 5 11 theme immunoglobulin 957:970 arg1 G 972:972 immunoglobulin G 957:972 immunoglobulin G (IgG) from human serum 957:995 The 19 typical N-linked glycopeptides were identified from 500 fmol tryptic digest of immunoglobulin G (IgG) from human serum by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis, meanwhile, 1919 unique glycopeptides with 1350 N-glycosylation sites from 605 different N-linked glycoproteins were identified from 100 μ g mouse liver tryptic digest by capillary liquid chromatography (cLC)-MS/MS analysis. 29048831 2 12 theme water 559:563 arg1 spectroscopy 386:397 Fourier-transform infrared spectroscopy 359:397 Fourier-transform infrared spectroscopy (FT-IR) 359:405 The physical properties of as-synthesized material were characterized by Fourier-transform infrared spectroscopy (FT-IR), solid-state cross polarisation magic angle spinning carbon-13 nuclear magnetic resonance (CP-MAS 13C NMR), nitrogen adsorption/desorption measurement, water contact angle and so on. 29048831 2 12 theme water 559:563 arg1 angle 573:577 water contact angle 559:577 water contact angle 559:577 The physical properties of as-synthesized material were characterized by Fourier-transform infrared spectroscopy (FT-IR), solid-state cross polarisation magic angle spinning carbon-13 nuclear magnetic resonance (CP-MAS 13C NMR), nitrogen adsorption/desorption measurement, water contact angle and so on. 29048831 5 13 with glycopeptides 1125:1137 arg1 sites 1165:1169 1350 N-glycosylation sites 1144:1169 1350 N-glycosylation sites 1144:1169 The 19 typical N-linked glycopeptides were identified from 500 fmol tryptic digest of immunoglobulin G (IgG) from human serum by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis, meanwhile, 1919 unique glycopeptides with 1350 N-glycosylation sites from 605 different N-linked glycoproteins were identified from 100 μ g mouse liver tryptic digest by capillary liquid chromatography (cLC)-MS/MS analysis. 29048831 5 14 theme N-glycosylation 1149:1163 arg1 sites 1165:1169 1350 N-glycosylation sites 1144:1169 1350 N-glycosylation sites 1144:1169 The 19 typical N-linked glycopeptides were identified from 500 fmol tryptic digest of immunoglobulin G (IgG) from human serum by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis, meanwhile, 1919 unique glycopeptides with 1350 N-glycosylation sites from 605 different N-linked glycoproteins were identified from 100 μ g mouse liver tryptic digest by capillary liquid chromatography (cLC)-MS/MS analysis. 29048831 3 15 theme contact 644:650 arg1 46.4° 662:666 46.4° 662:666 46.4° 662:666 The specific surface area was 166 m2/g, and the water contact angle was 46.4°, exhibiting hydrophilic property of the porous material. 29048831 3 15 theme contact 644:650 arg1 angle 652:656 the water contact angle 634:656 the water contact angle 634:656 The specific surface area was 166 m2/g, and the water contact angle was 46.4°, exhibiting hydrophilic property of the porous material. 29048831 5 16 gly glycoproteins 1199:1211 arg1 glycoproteins 1199:1211 605 different N-linked glycoproteins 1176:1211 605 different N-linked glycoproteins 1176:1211 The 19 typical N-linked glycopeptides were identified from 500 fmol tryptic digest of immunoglobulin G (IgG) from human serum by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis, meanwhile, 1919 unique glycopeptides with 1350 N-glycosylation sites from 605 different N-linked glycoproteins were identified from 100 μ g mouse liver tryptic digest by capillary liquid chromatography (cLC)-MS/MS analysis. 29048831 0 17 theme glycopeptides 91:103 arg1 enrichment 77:86 selective enrichment 67:86 selective enrichment of glycopeptides 67:103 [Fabrication of acylsemicarbazide-based porous organic polymer for selective enrichment of glycopeptides]. 29048831 4 18 from digest 800:805 arg1 mode 865:868 hydrophilic mode 853:868 hydrophilic mode 853:868 Thus, POP-1 was tried to be used for glycopeptides enrichment from tryptic digest of standard protein and complex biosamples in hydrophilic mode. 29048831 4 18 from digest 800:805 arg1 enrichment 776:785 glycopeptides enrichment 762:785 glycopeptides enrichment from tryptic digest of standard protein and complex biosamples in hydrophilic mode 762:868 Thus, POP-1 was tried to be used for glycopeptides enrichment from tryptic digest of standard protein and complex biosamples in hydrophilic mode. 29048831 5 19 theme fmol 934:937 arg1 digest 947:952 500 fmol tryptic digest 930:952 500 fmol tryptic digest of immunoglobulin G (IgG) from human serum 930:995 The 19 typical N-linked glycopeptides were identified from 500 fmol tryptic digest of immunoglobulin G (IgG) from human serum by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis, meanwhile, 1919 unique glycopeptides with 1350 N-glycosylation sites from 605 different N-linked glycoproteins were identified from 100 μ g mouse liver tryptic digest by capillary liquid chromatography (cLC)-MS/MS analysis. 29048831 5 20 theme unique 1118:1123 arg1 meanwhile 1102:1110 meanwhile 1102:1110 meanwhile 1102:1110 The 19 typical N-linked glycopeptides were identified from 500 fmol tryptic digest of immunoglobulin G (IgG) from human serum by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis, meanwhile, 1919 unique glycopeptides with 1350 N-glycosylation sites from 605 different N-linked glycoproteins were identified from 100 μ g mouse liver tryptic digest by capillary liquid chromatography (cLC)-MS/MS analysis. 29048831 5 20 theme unique 1118:1123 arg1 glycopeptides 1125:1137 1919 unique glycopeptides 1113:1137 1919 unique glycopeptides with 1350 N-glycosylation sites from 605 different N-linked glycoproteins 1113:1211 The 19 typical N-linked glycopeptides were identified from 500 fmol tryptic digest of immunoglobulin G (IgG) from human serum by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis, meanwhile, 1919 unique glycopeptides with 1350 N-glycosylation sites from 605 different N-linked glycoproteins were identified from 100 μ g mouse liver tryptic digest by capillary liquid chromatography (cLC)-MS/MS analysis. 29048831 5 21 theme human 985:989 arg1 serum 991:995 human serum 985:995 human serum 985:995 The 19 typical N-linked glycopeptides were identified from 500 fmol tryptic digest of immunoglobulin G (IgG) from human serum by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis, meanwhile, 1919 unique glycopeptides with 1350 N-glycosylation sites from 605 different N-linked glycoproteins were identified from 100 μ g mouse liver tryptic digest by capillary liquid chromatography (cLC)-MS/MS analysis. 29048831 4 22 gly glycopeptides 762:774 arg2 glycopeptides 762:774 glycopeptides enrichment 762:785 glycopeptides enrichment from tryptic digest of standard protein and complex biosamples in hydrophilic mode 762:868 Thus, POP-1 was tried to be used for glycopeptides enrichment from tryptic digest of standard protein and complex biosamples in hydrophilic mode. 29048831 2 23 theme 13C 505:507 arg1 resonance 487:495 carbon-13 nuclear magnetic resonance 460:495 carbon-13 nuclear magnetic resonance (CP-MAS 13C NMR) 460:512 The physical properties of as-synthesized material were characterized by Fourier-transform infrared spectroscopy (FT-IR), solid-state cross polarisation magic angle spinning carbon-13 nuclear magnetic resonance (CP-MAS 13C NMR), nitrogen adsorption/desorption measurement, water contact angle and so on. 29048831 2 23 theme 13C 505:507 arg1 NMR 509:511 CP-MAS 13C NMR 498:511 CP-MAS 13C NMR 498:511 The physical properties of as-synthesized material were characterized by Fourier-transform infrared spectroscopy (FT-IR), solid-state cross polarisation magic angle spinning carbon-13 nuclear magnetic resonance (CP-MAS 13C NMR), nitrogen adsorption/desorption measurement, water contact angle and so on. 29048831 2 24 theme polarisation 426:437 arg1 spectroscopy 386:397 Fourier-transform infrared spectroscopy 359:397 Fourier-transform infrared spectroscopy (FT-IR) 359:405 The physical properties of as-synthesized material were characterized by Fourier-transform infrared spectroscopy (FT-IR), solid-state cross polarisation magic angle spinning carbon-13 nuclear magnetic resonance (CP-MAS 13C NMR), nitrogen adsorption/desorption measurement, water contact angle and so on. 29048831 2 24 theme polarisation 426:437 arg1 angle 445:449 solid-state cross polarisation magic angle 408:449 solid-state cross polarisation magic angle spinning carbon-13 nuclear magnetic resonance (CP-MAS 13C NMR) 408:512 The physical properties of as-synthesized material were characterized by Fourier-transform infrared spectroscopy (FT-IR), solid-state cross polarisation magic angle spinning carbon-13 nuclear magnetic resonance (CP-MAS 13C NMR), nitrogen adsorption/desorption measurement, water contact angle and so on. 29048831 5 25 link N-linked 886:893 arg1 glycopeptides 895:907 The 19 typical N-linked glycopeptides 871:907 The 19 typical N-linked glycopeptides 871:907 The 19 typical N-linked glycopeptides were identified from 500 fmol tryptic digest of immunoglobulin G (IgG) from human serum by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis, meanwhile, 1919 unique glycopeptides with 1350 N-glycosylation sites from 605 different N-linked glycoproteins were identified from 100 μ g mouse liver tryptic digest by capillary liquid chromatography (cLC)-MS/MS analysis. 29048831 4 26 theme glycopeptides 762:774 arg1 enrichment 776:785 glycopeptides enrichment 762:785 glycopeptides enrichment from tryptic digest of standard protein and complex biosamples in hydrophilic mode 762:868 Thus, POP-1 was tried to be used for glycopeptides enrichment from tryptic digest of standard protein and complex biosamples in hydrophilic mode. 29048831 2 27 theme magnetic 478:485 arg1 resonance 487:495 carbon-13 nuclear magnetic resonance 460:495 carbon-13 nuclear magnetic resonance (CP-MAS 13C NMR) 460:512 The physical properties of as-synthesized material were characterized by Fourier-transform infrared spectroscopy (FT-IR), solid-state cross polarisation magic angle spinning carbon-13 nuclear magnetic resonance (CP-MAS 13C NMR), nitrogen adsorption/desorption measurement, water contact angle and so on. 29048831 2 27 theme magnetic 478:485 arg1 NMR 509:511 CP-MAS 13C NMR 498:511 CP-MAS 13C NMR 498:511 The physical properties of as-synthesized material were characterized by Fourier-transform infrared spectroscopy (FT-IR), solid-state cross polarisation magic angle spinning carbon-13 nuclear magnetic resonance (CP-MAS 13C NMR), nitrogen adsorption/desorption measurement, water contact angle and so on. 29048831 0 28 theme acylsemicarbazide-based 16:38 arg1 polymer 55:61 acylsemicarbazide-based porous organic polymer 16:61 acylsemicarbazide-based porous organic polymer 16:61 [Fabrication of acylsemicarbazide-based porous organic polymer for selective enrichment of glycopeptides]. 29048831 5 29 theme 100 1234:1236 arg1 μ 1238:1238 μ 1238:1238 μ 1238:1238 The 19 typical N-linked glycopeptides were identified from 500 fmol tryptic digest of immunoglobulin G (IgG) from human serum by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis, meanwhile, 1919 unique glycopeptides with 1350 N-glycosylation sites from 605 different N-linked glycoproteins were identified from 100 μ g mouse liver tryptic digest by capillary liquid chromatography (cLC)-MS/MS analysis. 29048831 1 30 theme porous 134:139 arg1 POP 158:160 POP 158:160 POP 158:160 An acylsemicarbazide-based porous organic polymer (POP) was facilely prepared by the polymerization of benzene-1,3,5-tricarbohydrazide (BTZ) and 1,4-phenylene diisocyanate (PDI). 29048831 1 30 theme porous 134:139 arg1 polymer 149:155 An acylsemicarbazide-based porous organic polymer 107:155 An acylsemicarbazide-based porous organic polymer (POP) 107:161 An acylsemicarbazide-based porous organic polymer (POP) was facilely prepared by the polymerization of benzene-1,3,5-tricarbohydrazide (BTZ) and 1,4-phenylene diisocyanate (PDI). 29048831 2 31 theme nitrogen 515:522 arg1 spectroscopy 386:397 Fourier-transform infrared spectroscopy 359:397 Fourier-transform infrared spectroscopy (FT-IR) 359:405 The physical properties of as-synthesized material were characterized by Fourier-transform infrared spectroscopy (FT-IR), solid-state cross polarisation magic angle spinning carbon-13 nuclear magnetic resonance (CP-MAS 13C NMR), nitrogen adsorption/desorption measurement, water contact angle and so on. 29048831 2 31 theme nitrogen 515:522 arg1 measurement 546:556 nitrogen adsorption/desorption measurement 515:556 nitrogen adsorption/desorption measurement 515:556 The physical properties of as-synthesized material were characterized by Fourier-transform infrared spectroscopy (FT-IR), solid-state cross polarisation magic angle spinning carbon-13 nuclear magnetic resonance (CP-MAS 13C NMR), nitrogen adsorption/desorption measurement, water contact angle and so on. 29048831 3 32 theme hydrophilic 680:690 arg1 property 692:699 hydrophilic property 680:699 hydrophilic property of the porous material 680:722 The specific surface area was 166 m2/g, and the water contact angle was 46.4°, exhibiting hydrophilic property of the porous material. 29048831 4 33 theme biosamples 839:848 arg1 digest 800:805 tryptic digest 792:805 tryptic digest of standard protein and complex biosamples in hydrophilic mode 792:868 Thus, POP-1 was tried to be used for glycopeptides enrichment from tryptic digest of standard protein and complex biosamples in hydrophilic mode. 29048831 2 34 theme carbon-13 460:468 arg1 resonance 487:495 carbon-13 nuclear magnetic resonance 460:495 carbon-13 nuclear magnetic resonance (CP-MAS 13C NMR) 460:512 The physical properties of as-synthesized material were characterized by Fourier-transform infrared spectroscopy (FT-IR), solid-state cross polarisation magic angle spinning carbon-13 nuclear magnetic resonance (CP-MAS 13C NMR), nitrogen adsorption/desorption measurement, water contact angle and so on. 29048831 2 34 theme carbon-13 460:468 arg1 NMR 509:511 CP-MAS 13C NMR 498:511 CP-MAS 13C NMR 498:511 The physical properties of as-synthesized material were characterized by Fourier-transform infrared spectroscopy (FT-IR), solid-state cross polarisation magic angle spinning carbon-13 nuclear magnetic resonance (CP-MAS 13C NMR), nitrogen adsorption/desorption measurement, water contact angle and so on. 29048831 0 35 theme organic 47:53 arg1 polymer 55:61 acylsemicarbazide-based porous organic polymer 16:61 acylsemicarbazide-based porous organic polymer 16:61 [Fabrication of acylsemicarbazide-based porous organic polymer for selective enrichment of glycopeptides]. 29048831 5 36 theme different 1180:1188 arg1 glycoproteins 1199:1211 605 different N-linked glycoproteins 1176:1211 605 different N-linked glycoproteins 1176:1211 The 19 typical N-linked glycopeptides were identified from 500 fmol tryptic digest of immunoglobulin G (IgG) from human serum by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis, meanwhile, 1919 unique glycopeptides with 1350 N-glycosylation sites from 605 different N-linked glycoproteins were identified from 100 μ g mouse liver tryptic digest by capillary liquid chromatography (cLC)-MS/MS analysis. 29048831 5 37 theme flight 1052:1057 arg1 MALDI-TOF/MS 1078:1089 MALDI-TOF/MS 1078:1089 MALDI-TOF/MS 1078:1089 The 19 typical N-linked glycopeptides were identified from 500 fmol tryptic digest of immunoglobulin G (IgG) from human serum by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis, meanwhile, 1919 unique glycopeptides with 1350 N-glycosylation sites from 605 different N-linked glycoproteins were identified from 100 μ g mouse liver tryptic digest by capillary liquid chromatography (cLC)-MS/MS analysis. 29048831 5 37 theme flight 1052:1057 arg1 spectrometry 1064:1075 flight mass spectrometry 1052:1075 flight mass spectrometry (MALDI-TOF/MS) analysis 1052:1099 The 19 typical N-linked glycopeptides were identified from 500 fmol tryptic digest of immunoglobulin G (IgG) from human serum by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis, meanwhile, 1919 unique glycopeptides with 1350 N-glycosylation sites from 605 different N-linked glycoproteins were identified from 100 μ g mouse liver tryptic digest by capillary liquid chromatography (cLC)-MS/MS analysis. 29048831 4 38 theme hydrophilic 853:863 arg1 mode 865:868 hydrophilic mode 853:868 hydrophilic mode 853:868 Thus, POP-1 was tried to be used for glycopeptides enrichment from tryptic digest of standard protein and complex biosamples in hydrophilic mode. 29048831 5 39 theme spectrometry 1064:1075 arg1 analysis 1092:1099 flight mass spectrometry (MALDI-TOF/MS) analysis 1052:1099 flight mass spectrometry (MALDI-TOF/MS) analysis 1052:1099 The 19 typical N-linked glycopeptides were identified from 500 fmol tryptic digest of immunoglobulin G (IgG) from human serum by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis, meanwhile, 1919 unique glycopeptides with 1350 N-glycosylation sites from 605 different N-linked glycoproteins were identified from 100 μ g mouse liver tryptic digest by capillary liquid chromatography (cLC)-MS/MS analysis. 29048831 3 40 theme porous 708:713 arg1 material 715:722 the porous material 704:722 the porous material 704:722 The specific surface area was 166 m2/g, and the water contact angle was 46.4°, exhibiting hydrophilic property of the porous material. 29048831 4 41 theme standard 810:817 arg1 protein 819:825 standard protein and complex biosamples 810:848 protein 819:825 Thus, POP-1 was tried to be used for glycopeptides enrichment from tryptic digest of standard protein and complex biosamples in hydrophilic mode. 29048831 2 42 theme infrared 377:384 arg1 angle 573:577 water contact angle 559:577 water contact angle 559:577 The physical properties of as-synthesized material were characterized by Fourier-transform infrared spectroscopy (FT-IR), solid-state cross polarisation magic angle spinning carbon-13 nuclear magnetic resonance (CP-MAS 13C NMR), nitrogen adsorption/desorption measurement, water contact angle and so on. 29048831 2 42 theme infrared 377:384 arg1 angle 445:449 solid-state cross polarisation magic angle 408:449 solid-state cross polarisation magic angle spinning carbon-13 nuclear magnetic resonance (CP-MAS 13C NMR) 408:512 The physical properties of as-synthesized material were characterized by Fourier-transform infrared spectroscopy (FT-IR), solid-state cross polarisation magic angle spinning carbon-13 nuclear magnetic resonance (CP-MAS 13C NMR), nitrogen adsorption/desorption measurement, water contact angle and so on. 29048831 2 42 theme infrared 377:384 arg1 FT-IR 400:404 FT-IR 400:404 FT-IR 400:404 The physical properties of as-synthesized material were characterized by Fourier-transform infrared spectroscopy (FT-IR), solid-state cross polarisation magic angle spinning carbon-13 nuclear magnetic resonance (CP-MAS 13C NMR), nitrogen adsorption/desorption measurement, water contact angle and so on. 29048831 2 42 theme infrared 377:384 arg1 so 583:584 so 583:584 so 583:584 The physical properties of as-synthesized material were characterized by Fourier-transform infrared spectroscopy (FT-IR), solid-state cross polarisation magic angle spinning carbon-13 nuclear magnetic resonance (CP-MAS 13C NMR), nitrogen adsorption/desorption measurement, water contact angle and so on. 29048831 2 42 theme infrared 377:384 arg1 measurement 546:556 nitrogen adsorption/desorption measurement 515:556 nitrogen adsorption/desorption measurement 515:556 The physical properties of as-synthesized material were characterized by Fourier-transform infrared spectroscopy (FT-IR), solid-state cross polarisation magic angle spinning carbon-13 nuclear magnetic resonance (CP-MAS 13C NMR), nitrogen adsorption/desorption measurement, water contact angle and so on. 29048831 2 42 theme infrared 377:384 arg1 spectroscopy 386:397 Fourier-transform infrared spectroscopy 359:397 Fourier-transform infrared spectroscopy (FT-IR) 359:405 The physical properties of as-synthesized material were characterized by Fourier-transform infrared spectroscopy (FT-IR), solid-state cross polarisation magic angle spinning carbon-13 nuclear magnetic resonance (CP-MAS 13C NMR), nitrogen adsorption/desorption measurement, water contact angle and so on. 29048831 5 43 theme laser 1016:1020 arg1 ionization-time 1033:1047 matrix-assisted laser desorption ionization-time 1000:1047 matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis 1000:1099 The 19 typical N-linked glycopeptides were identified from 500 fmol tryptic digest of immunoglobulin G (IgG) from human serum by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis, meanwhile, 1919 unique glycopeptides with 1350 N-glycosylation sites from 605 different N-linked glycoproteins were identified from 100 μ g mouse liver tryptic digest by capillary liquid chromatography (cLC)-MS/MS analysis. 29048831 2 44 theme solid-state 408:418 arg1 spectroscopy 386:397 Fourier-transform infrared spectroscopy 359:397 Fourier-transform infrared spectroscopy (FT-IR) 359:405 The physical properties of as-synthesized material were characterized by Fourier-transform infrared spectroscopy (FT-IR), solid-state cross polarisation magic angle spinning carbon-13 nuclear magnetic resonance (CP-MAS 13C NMR), nitrogen adsorption/desorption measurement, water contact angle and so on. 29048831 2 44 theme solid-state 408:418 arg1 angle 445:449 solid-state cross polarisation magic angle 408:449 solid-state cross polarisation magic angle spinning carbon-13 nuclear magnetic resonance (CP-MAS 13C NMR) 408:512 The physical properties of as-synthesized material were characterized by Fourier-transform infrared spectroscopy (FT-IR), solid-state cross polarisation magic angle spinning carbon-13 nuclear magnetic resonance (CP-MAS 13C NMR), nitrogen adsorption/desorption measurement, water contact angle and so on. 29048831 1 45 theme diisocyanate 266:277 arg1 polymerization 192:205 the polymerization 188:205 the polymerization of benzene-1,3,5-tricarbohydrazide (BTZ) and 1,4-phenylene diisocyanate (PDI) 188:283 An acylsemicarbazide-based porous organic polymer (POP) was facilely prepared by the polymerization of benzene-1,3,5-tricarbohydrazide (BTZ) and 1,4-phenylene diisocyanate (PDI). 29048831 5 46 from glycoproteins 1199:1211 arg1 meanwhile 1102:1110 meanwhile 1102:1110 meanwhile 1102:1110 The 19 typical N-linked glycopeptides were identified from 500 fmol tryptic digest of immunoglobulin G (IgG) from human serum by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis, meanwhile, 1919 unique glycopeptides with 1350 N-glycosylation sites from 605 different N-linked glycoproteins were identified from 100 μ g mouse liver tryptic digest by capillary liquid chromatography (cLC)-MS/MS analysis. 29048831 5 46 from glycoproteins 1199:1211 arg1 glycopeptides 1125:1137 1919 unique glycopeptides 1113:1137 1919 unique glycopeptides with 1350 N-glycosylation sites from 605 different N-linked glycoproteins 1113:1211 The 19 typical N-linked glycopeptides were identified from 500 fmol tryptic digest of immunoglobulin G (IgG) from human serum by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis, meanwhile, 1919 unique glycopeptides with 1350 N-glycosylation sites from 605 different N-linked glycoproteins were identified from 100 μ g mouse liver tryptic digest by capillary liquid chromatography (cLC)-MS/MS analysis. 29048831 5 47 theme g 1240:1240 arg1 digest 1262:1267 100 μ g mouse liver tryptic digest 1234:1267 100 μ g mouse liver tryptic digest 1234:1267 The 19 typical N-linked glycopeptides were identified from 500 fmol tryptic digest of immunoglobulin G (IgG) from human serum by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis, meanwhile, 1919 unique glycopeptides with 1350 N-glycosylation sites from 605 different N-linked glycoproteins were identified from 100 μ g mouse liver tryptic digest by capillary liquid chromatography (cLC)-MS/MS analysis. 29048831 2 48 theme as-synthesized 313:326 arg1 material 328:335 as-synthesized material 313:335 as-synthesized material 313:335 The physical properties of as-synthesized material were characterized by Fourier-transform infrared spectroscopy (FT-IR), solid-state cross polarisation magic angle spinning carbon-13 nuclear magnetic resonance (CP-MAS 13C NMR), nitrogen adsorption/desorption measurement, water contact angle and so on. 29048831 4 49 used used 753:756 arg2 POP-1 731:735 POP-1 731:735 POP-1 731:735 Thus, POP-1 was tried to be used for glycopeptides enrichment from tryptic digest of standard protein and complex biosamples in hydrophilic mode. 29048831 5 50 theme liver 1248:1252 arg1 digest 1262:1267 100 μ g mouse liver tryptic digest 1234:1267 100 μ g mouse liver tryptic digest 1234:1267 The 19 typical N-linked glycopeptides were identified from 500 fmol tryptic digest of immunoglobulin G (IgG) from human serum by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis, meanwhile, 1919 unique glycopeptides with 1350 N-glycosylation sites from 605 different N-linked glycoproteins were identified from 100 μ g mouse liver tryptic digest by capillary liquid chromatography (cLC)-MS/MS analysis. 29048831 5 51 gly glycopeptides 895:907 arg2 glycopeptides 895:907 The 19 typical N-linked glycopeptides 871:907 The 19 typical N-linked glycopeptides 871:907 The 19 typical N-linked glycopeptides were identified from 500 fmol tryptic digest of immunoglobulin G (IgG) from human serum by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis, meanwhile, 1919 unique glycopeptides with 1350 N-glycosylation sites from 605 different N-linked glycoproteins were identified from 100 μ g mouse liver tryptic digest by capillary liquid chromatography (cLC)-MS/MS analysis. 29048831 5 52 theme typical 878:884 arg1 glycopeptides 895:907 The 19 typical N-linked glycopeptides 871:907 The 19 typical N-linked glycopeptides 871:907 The 19 typical N-linked glycopeptides were identified from 500 fmol tryptic digest of immunoglobulin G (IgG) from human serum by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis, meanwhile, 1919 unique glycopeptides with 1350 N-glycosylation sites from 605 different N-linked glycoproteins were identified from 100 μ g mouse liver tryptic digest by capillary liquid chromatography (cLC)-MS/MS analysis. 29048831 5 53 gly glycopeptides 1125:1137 arg1 glycoproteins 1199:1211 605 different N-linked glycoproteins 1176:1211 605 different N-linked glycoproteins 1176:1211 The 19 typical N-linked glycopeptides were identified from 500 fmol tryptic digest of immunoglobulin G (IgG) from human serum by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis, meanwhile, 1919 unique glycopeptides with 1350 N-glycosylation sites from 605 different N-linked glycoproteins were identified from 100 μ g mouse liver tryptic digest by capillary liquid chromatography (cLC)-MS/MS analysis. 29048831 5 53 gly glycopeptides 1125:1137 arg2 meanwhile 1102:1110 meanwhile 1102:1110 meanwhile 1102:1110 The 19 typical N-linked glycopeptides were identified from 500 fmol tryptic digest of immunoglobulin G (IgG) from human serum by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis, meanwhile, 1919 unique glycopeptides with 1350 N-glycosylation sites from 605 different N-linked glycoproteins were identified from 100 μ g mouse liver tryptic digest by capillary liquid chromatography (cLC)-MS/MS analysis. 29048831 5 53 gly glycopeptides 1125:1137 arg2 glycopeptides 1125:1137 1919 unique glycopeptides 1113:1137 1919 unique glycopeptides with 1350 N-glycosylation sites from 605 different N-linked glycoproteins 1113:1211 The 19 typical N-linked glycopeptides were identified from 500 fmol tryptic digest of immunoglobulin G (IgG) from human serum by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis, meanwhile, 1919 unique glycopeptides with 1350 N-glycosylation sites from 605 different N-linked glycoproteins were identified from 100 μ g mouse liver tryptic digest by capillary liquid chromatography (cLC)-MS/MS analysis. 29048831 3 54 theme surface 603:609 arg1 area 611:614 The specific surface area 590:614 The specific surface area 590:614 The specific surface area was 166 m2/g, and the water contact angle was 46.4°, exhibiting hydrophilic property of the porous material. 29048831 3 54 theme surface 603:609 arg1 m2/g 624:627 166 m2/g 620:627 166 m2/g 620:627 The specific surface area was 166 m2/g, and the water contact angle was 46.4°, exhibiting hydrophilic property of the porous material. 29048831 1 55 theme benzene-1,3,5-tricarbohydrazide 210:240 arg1 polymerization 192:205 the polymerization 188:205 the polymerization of benzene-1,3,5-tricarbohydrazide (BTZ) and 1,4-phenylene diisocyanate (PDI) 188:283 An acylsemicarbazide-based porous organic polymer (POP) was facilely prepared by the polymerization of benzene-1,3,5-tricarbohydrazide (BTZ) and 1,4-phenylene diisocyanate (PDI). 29048831 6 56 theme great 1357:1361 arg1 potential 1363:1371 the great potential 1353:1371 the great potential of POP-1 for glycoproteome analysis 1353:1407 These results demonstrated the great potential of POP-1 for glycoproteome analysis. 29048831 5 57 theme tryptic 939:945 arg1 digest 947:952 500 fmol tryptic digest 930:952 500 fmol tryptic digest of immunoglobulin G (IgG) from human serum 930:995 The 19 typical N-linked glycopeptides were identified from 500 fmol tryptic digest of immunoglobulin G (IgG) from human serum by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis, meanwhile, 1919 unique glycopeptides with 1350 N-glycosylation sites from 605 different N-linked glycoproteins were identified from 100 μ g mouse liver tryptic digest by capillary liquid chromatography (cLC)-MS/MS analysis. 29048831 5 58 theme -MS/MS 1309:1314 arg1 analysis 1316:1323 capillary liquid chromatography (cLC)-MS/MS analysis 1272:1323 capillary liquid chromatography (cLC)-MS/MS analysis 1272:1323 The 19 typical N-linked glycopeptides were identified from 500 fmol tryptic digest of immunoglobulin G (IgG) from human serum by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis, meanwhile, 1919 unique glycopeptides with 1350 N-glycosylation sites from 605 different N-linked glycoproteins were identified from 100 μ g mouse liver tryptic digest by capillary liquid chromatography (cLC)-MS/MS analysis. 29048831 5 59 theme analysis 1092:1099 arg1 ionization-time 1033:1047 matrix-assisted laser desorption ionization-time 1000:1047 matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis 1000:1099 The 19 typical N-linked glycopeptides were identified from 500 fmol tryptic digest of immunoglobulin G (IgG) from human serum by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis, meanwhile, 1919 unique glycopeptides with 1350 N-glycosylation sites from 605 different N-linked glycoproteins were identified from 100 μ g mouse liver tryptic digest by capillary liquid chromatography (cLC)-MS/MS analysis. 29048831 3 60 theme water 638:642 arg1 46.4° 662:666 46.4° 662:666 46.4° 662:666 The specific surface area was 166 m2/g, and the water contact angle was 46.4°, exhibiting hydrophilic property of the porous material. 29048831 3 60 theme water 638:642 arg1 angle 652:656 the water contact angle 634:656 the water contact angle 634:656 The specific surface area was 166 m2/g, and the water contact angle was 46.4°, exhibiting hydrophilic property of the porous material. 29048831 4 61 from protein 819:825 arg1 mode 865:868 hydrophilic mode 853:868 hydrophilic mode 853:868 Thus, POP-1 was tried to be used for glycopeptides enrichment from tryptic digest of standard protein and complex biosamples in hydrophilic mode. 29048831 5 62 theme chromatography 1289:1302 arg1 analysis 1316:1323 capillary liquid chromatography (cLC)-MS/MS analysis 1272:1323 capillary liquid chromatography (cLC)-MS/MS analysis 1272:1323 The 19 typical N-linked glycopeptides were identified from 500 fmol tryptic digest of immunoglobulin G (IgG) from human serum by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis, meanwhile, 1919 unique glycopeptides with 1350 N-glycosylation sites from 605 different N-linked glycoproteins were identified from 100 μ g mouse liver tryptic digest by capillary liquid chromatography (cLC)-MS/MS analysis. 29048831 5 63 theme 500 930:932 arg1 fmol 934:937 fmol 934:937 fmol 934:937 The 19 typical N-linked glycopeptides were identified from 500 fmol tryptic digest of immunoglobulin G (IgG) from human serum by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis, meanwhile, 1919 unique glycopeptides with 1350 N-glycosylation sites from 605 different N-linked glycoproteins were identified from 100 μ g mouse liver tryptic digest by capillary liquid chromatography (cLC)-MS/MS analysis. 29048831 2 64 theme adsorption/desorption 524:544 arg1 spectroscopy 386:397 Fourier-transform infrared spectroscopy 359:397 Fourier-transform infrared spectroscopy (FT-IR) 359:405 The physical properties of as-synthesized material were characterized by Fourier-transform infrared spectroscopy (FT-IR), solid-state cross polarisation magic angle spinning carbon-13 nuclear magnetic resonance (CP-MAS 13C NMR), nitrogen adsorption/desorption measurement, water contact angle and so on. 29048831 2 64 theme adsorption/desorption 524:544 arg1 measurement 546:556 nitrogen adsorption/desorption measurement 515:556 nitrogen adsorption/desorption measurement 515:556 The physical properties of as-synthesized material were characterized by Fourier-transform infrared spectroscopy (FT-IR), solid-state cross polarisation magic angle spinning carbon-13 nuclear magnetic resonance (CP-MAS 13C NMR), nitrogen adsorption/desorption measurement, water contact angle and so on. 29048831 0 65 gly glycopeptides 91:103 arg2 glycopeptides 91:103 glycopeptides 91:103 glycopeptides 91:103 [Fabrication of acylsemicarbazide-based porous organic polymer for selective enrichment of glycopeptides]. 29048831 2 66 theme contact 565:571 arg1 spectroscopy 386:397 Fourier-transform infrared spectroscopy 359:397 Fourier-transform infrared spectroscopy (FT-IR) 359:405 The physical properties of as-synthesized material were characterized by Fourier-transform infrared spectroscopy (FT-IR), solid-state cross polarisation magic angle spinning carbon-13 nuclear magnetic resonance (CP-MAS 13C NMR), nitrogen adsorption/desorption measurement, water contact angle and so on. 29048831 2 66 theme contact 565:571 arg1 angle 573:577 water contact angle 559:577 water contact angle 559:577 The physical properties of as-synthesized material were characterized by Fourier-transform infrared spectroscopy (FT-IR), solid-state cross polarisation magic angle spinning carbon-13 nuclear magnetic resonance (CP-MAS 13C NMR), nitrogen adsorption/desorption measurement, water contact angle and so on. 29048831 4 67 theme tryptic 792:798 arg1 digest 800:805 tryptic digest 792:805 tryptic digest of standard protein and complex biosamples in hydrophilic mode 792:868 Thus, POP-1 was tried to be used for glycopeptides enrichment from tryptic digest of standard protein and complex biosamples in hydrophilic mode. 29048831 2 68 theme magic 439:443 arg1 spectroscopy 386:397 Fourier-transform infrared spectroscopy 359:397 Fourier-transform infrared spectroscopy (FT-IR) 359:405 The physical properties of as-synthesized material were characterized by Fourier-transform infrared spectroscopy (FT-IR), solid-state cross polarisation magic angle spinning carbon-13 nuclear magnetic resonance (CP-MAS 13C NMR), nitrogen adsorption/desorption measurement, water contact angle and so on. 29048831 2 68 theme magic 439:443 arg1 angle 445:449 solid-state cross polarisation magic angle 408:449 solid-state cross polarisation magic angle spinning carbon-13 nuclear magnetic resonance (CP-MAS 13C NMR) 408:512 The physical properties of as-synthesized material were characterized by Fourier-transform infrared spectroscopy (FT-IR), solid-state cross polarisation magic angle spinning carbon-13 nuclear magnetic resonance (CP-MAS 13C NMR), nitrogen adsorption/desorption measurement, water contact angle and so on. 29048831 4 69 from mode 865:868 arg1 digest 800:805 tryptic digest 792:805 tryptic digest of standard protein and complex biosamples in hydrophilic mode 792:868 Thus, POP-1 was tried to be used for glycopeptides enrichment from tryptic digest of standard protein and complex biosamples in hydrophilic mode. 29048831 5 70 theme G 972:972 arg1 digest 947:952 500 fmol tryptic digest 930:952 500 fmol tryptic digest of immunoglobulin G (IgG) from human serum 930:995 The 19 typical N-linked glycopeptides were identified from 500 fmol tryptic digest of immunoglobulin G (IgG) from human serum by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis, meanwhile, 1919 unique glycopeptides with 1350 N-glycosylation sites from 605 different N-linked glycoproteins were identified from 100 μ g mouse liver tryptic digest by capillary liquid chromatography (cLC)-MS/MS analysis. 29048831 2 71 theme CP-MAS 498:503 arg1 resonance 487:495 carbon-13 nuclear magnetic resonance 460:495 carbon-13 nuclear magnetic resonance (CP-MAS 13C NMR) 460:512 The physical properties of as-synthesized material were characterized by Fourier-transform infrared spectroscopy (FT-IR), solid-state cross polarisation magic angle spinning carbon-13 nuclear magnetic resonance (CP-MAS 13C NMR), nitrogen adsorption/desorption measurement, water contact angle and so on. 29048831 2 71 theme CP-MAS 498:503 arg1 NMR 509:511 CP-MAS 13C NMR 498:511 CP-MAS 13C NMR 498:511 The physical properties of as-synthesized material were characterized by Fourier-transform infrared spectroscopy (FT-IR), solid-state cross polarisation magic angle spinning carbon-13 nuclear magnetic resonance (CP-MAS 13C NMR), nitrogen adsorption/desorption measurement, water contact angle and so on. 29048831 2 72 theme cross 420:424 arg1 spectroscopy 386:397 Fourier-transform infrared spectroscopy 359:397 Fourier-transform infrared spectroscopy (FT-IR) 359:405 The physical properties of as-synthesized material were characterized by Fourier-transform infrared spectroscopy (FT-IR), solid-state cross polarisation magic angle spinning carbon-13 nuclear magnetic resonance (CP-MAS 13C NMR), nitrogen adsorption/desorption measurement, water contact angle and so on. 29048831 2 72 theme cross 420:424 arg1 angle 445:449 solid-state cross polarisation magic angle 408:449 solid-state cross polarisation magic angle spinning carbon-13 nuclear magnetic resonance (CP-MAS 13C NMR) 408:512 The physical properties of as-synthesized material were characterized by Fourier-transform infrared spectroscopy (FT-IR), solid-state cross polarisation magic angle spinning carbon-13 nuclear magnetic resonance (CP-MAS 13C NMR), nitrogen adsorption/desorption measurement, water contact angle and so on. 29048831 0 73 theme porous 40:45 arg1 polymer 55:61 acylsemicarbazide-based porous organic polymer 16:61 acylsemicarbazide-based porous organic polymer 16:61 [Fabrication of acylsemicarbazide-based porous organic polymer for selective enrichment of glycopeptides]. 29048831 5 74 from digest 947:952 arg1 serum 991:995 human serum 985:995 human serum 985:995 The 19 typical N-linked glycopeptides were identified from 500 fmol tryptic digest of immunoglobulin G (IgG) from human serum by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis, meanwhile, 1919 unique glycopeptides with 1350 N-glycosylation sites from 605 different N-linked glycoproteins were identified from 100 μ g mouse liver tryptic digest by capillary liquid chromatography (cLC)-MS/MS analysis. 29048831 1 75 theme acylsemicarbazide-based 110:132 arg1 POP 158:160 POP 158:160 POP 158:160 An acylsemicarbazide-based porous organic polymer (POP) was facilely prepared by the polymerization of benzene-1,3,5-tricarbohydrazide (BTZ) and 1,4-phenylene diisocyanate (PDI). 29048831 1 75 theme acylsemicarbazide-based 110:132 arg1 polymer 149:155 An acylsemicarbazide-based porous organic polymer 107:155 An acylsemicarbazide-based porous organic polymer (POP) 107:161 An acylsemicarbazide-based porous organic polymer (POP) was facilely prepared by the polymerization of benzene-1,3,5-tricarbohydrazide (BTZ) and 1,4-phenylene diisocyanate (PDI). 29048831 2 76 theme nuclear 470:476 arg1 resonance 487:495 carbon-13 nuclear magnetic resonance 460:495 carbon-13 nuclear magnetic resonance (CP-MAS 13C NMR) 460:512 The physical properties of as-synthesized material were characterized by Fourier-transform infrared spectroscopy (FT-IR), solid-state cross polarisation magic angle spinning carbon-13 nuclear magnetic resonance (CP-MAS 13C NMR), nitrogen adsorption/desorption measurement, water contact angle and so on. 29048831 2 76 theme nuclear 470:476 arg1 NMR 509:511 CP-MAS 13C NMR 498:511 CP-MAS 13C NMR 498:511 The physical properties of as-synthesized material were characterized by Fourier-transform infrared spectroscopy (FT-IR), solid-state cross polarisation magic angle spinning carbon-13 nuclear magnetic resonance (CP-MAS 13C NMR), nitrogen adsorption/desorption measurement, water contact angle and so on. 29048831 0 77 theme polymer 55:61 arg1 [Fabrication 0:11 [Fabrication 0:11 [Fabrication of acylsemicarbazide-based porous organic polymer for selective enrichment of glycopeptides 0:103 [Fabrication of acylsemicarbazide-based porous organic polymer for selective enrichment of glycopeptides]. 29048831 5 78 theme μ 1238:1238 arg1 digest 1262:1267 100 μ g mouse liver tryptic digest 1234:1267 100 μ g mouse liver tryptic digest 1234:1267 The 19 typical N-linked glycopeptides were identified from 500 fmol tryptic digest of immunoglobulin G (IgG) from human serum by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis, meanwhile, 1919 unique glycopeptides with 1350 N-glycosylation sites from 605 different N-linked glycoproteins were identified from 100 μ g mouse liver tryptic digest by capillary liquid chromatography (cLC)-MS/MS analysis. 29048831 4 79 theme complex 831:837 arg1 biosamples 839:848 standard protein and complex biosamples 810:848 biosamples 839:848 Thus, POP-1 was tried to be used for glycopeptides enrichment from tryptic digest of standard protein and complex biosamples in hydrophilic mode. 29048831 6 80 theme glycoproteome 1386:1398 arg1 analysis 1400:1407 glycoproteome analysis 1386:1407 glycoproteome analysis 1386:1407 These results demonstrated the great potential of POP-1 for glycoproteome analysis. 29048831 0 81 theme selective 67:75 arg1 enrichment 77:86 selective enrichment 67:86 selective enrichment of glycopeptides 67:103 [Fabrication of acylsemicarbazide-based porous organic polymer for selective enrichment of glycopeptides]. 29048831 5 82 theme N-linked 1190:1197 arg1 glycoproteins 1199:1211 605 different N-linked glycoproteins 1176:1211 605 different N-linked glycoproteins 1176:1211 The 19 typical N-linked glycopeptides were identified from 500 fmol tryptic digest of immunoglobulin G (IgG) from human serum by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis, meanwhile, 1919 unique glycopeptides with 1350 N-glycosylation sites from 605 different N-linked glycoproteins were identified from 100 μ g mouse liver tryptic digest by capillary liquid chromatography (cLC)-MS/MS analysis. 29048831 5 83 theme mass 1059:1062 arg1 MALDI-TOF/MS 1078:1089 MALDI-TOF/MS 1078:1089 MALDI-TOF/MS 1078:1089 The 19 typical N-linked glycopeptides were identified from 500 fmol tryptic digest of immunoglobulin G (IgG) from human serum by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis, meanwhile, 1919 unique glycopeptides with 1350 N-glycosylation sites from 605 different N-linked glycoproteins were identified from 100 μ g mouse liver tryptic digest by capillary liquid chromatography (cLC)-MS/MS analysis. 29048831 5 83 theme mass 1059:1062 arg1 spectrometry 1064:1075 flight mass spectrometry 1052:1075 flight mass spectrometry (MALDI-TOF/MS) analysis 1052:1099 The 19 typical N-linked glycopeptides were identified from 500 fmol tryptic digest of immunoglobulin G (IgG) from human serum by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis, meanwhile, 1919 unique glycopeptides with 1350 N-glycosylation sites from 605 different N-linked glycoproteins were identified from 100 μ g mouse liver tryptic digest by capillary liquid chromatography (cLC)-MS/MS analysis. 29048831 5 84 theme matrix-assisted 1000:1014 arg1 ionization-time 1033:1047 matrix-assisted laser desorption ionization-time 1000:1047 matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis 1000:1099 The 19 typical N-linked glycopeptides were identified from 500 fmol tryptic digest of immunoglobulin G (IgG) from human serum by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis, meanwhile, 1919 unique glycopeptides with 1350 N-glycosylation sites from 605 different N-linked glycoproteins were identified from 100 μ g mouse liver tryptic digest by capillary liquid chromatography (cLC)-MS/MS analysis. 29048831 5 85 link N-linked 1190:1197 arg1 glycoproteins 1199:1211 605 different N-linked glycoproteins 1176:1211 605 different N-linked glycoproteins 1176:1211 The 19 typical N-linked glycopeptides were identified from 500 fmol tryptic digest of immunoglobulin G (IgG) from human serum by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis, meanwhile, 1919 unique glycopeptides with 1350 N-glycosylation sites from 605 different N-linked glycoproteins were identified from 100 μ g mouse liver tryptic digest by capillary liquid chromatography (cLC)-MS/MS analysis. 29048831 2 86 theme Fourier-transform 359:375 arg1 angle 573:577 water contact angle 559:577 water contact angle 559:577 The physical properties of as-synthesized material were characterized by Fourier-transform infrared spectroscopy (FT-IR), solid-state cross polarisation magic angle spinning carbon-13 nuclear magnetic resonance (CP-MAS 13C NMR), nitrogen adsorption/desorption measurement, water contact angle and so on. 29048831 2 86 theme Fourier-transform 359:375 arg1 angle 445:449 solid-state cross polarisation magic angle 408:449 solid-state cross polarisation magic angle spinning carbon-13 nuclear magnetic resonance (CP-MAS 13C NMR) 408:512 The physical properties of as-synthesized material were characterized by Fourier-transform infrared spectroscopy (FT-IR), solid-state cross polarisation magic angle spinning carbon-13 nuclear magnetic resonance (CP-MAS 13C NMR), nitrogen adsorption/desorption measurement, water contact angle and so on. 29048831 2 86 theme Fourier-transform 359:375 arg1 FT-IR 400:404 FT-IR 400:404 FT-IR 400:404 The physical properties of as-synthesized material were characterized by Fourier-transform infrared spectroscopy (FT-IR), solid-state cross polarisation magic angle spinning carbon-13 nuclear magnetic resonance (CP-MAS 13C NMR), nitrogen adsorption/desorption measurement, water contact angle and so on. 29048831 2 86 theme Fourier-transform 359:375 arg1 so 583:584 so 583:584 so 583:584 The physical properties of as-synthesized material were characterized by Fourier-transform infrared spectroscopy (FT-IR), solid-state cross polarisation magic angle spinning carbon-13 nuclear magnetic resonance (CP-MAS 13C NMR), nitrogen adsorption/desorption measurement, water contact angle and so on. 29048831 2 86 theme Fourier-transform 359:375 arg1 measurement 546:556 nitrogen adsorption/desorption measurement 515:556 nitrogen adsorption/desorption measurement 515:556 The physical properties of as-synthesized material were characterized by Fourier-transform infrared spectroscopy (FT-IR), solid-state cross polarisation magic angle spinning carbon-13 nuclear magnetic resonance (CP-MAS 13C NMR), nitrogen adsorption/desorption measurement, water contact angle and so on. 29048831 2 86 theme Fourier-transform 359:375 arg1 spectroscopy 386:397 Fourier-transform infrared spectroscopy 359:397 Fourier-transform infrared spectroscopy (FT-IR) 359:405 The physical properties of as-synthesized material were characterized by Fourier-transform infrared spectroscopy (FT-IR), solid-state cross polarisation magic angle spinning carbon-13 nuclear magnetic resonance (CP-MAS 13C NMR), nitrogen adsorption/desorption measurement, water contact angle and so on. 29048831 1 87 theme 1,4-phenylene 252:264 arg1 diisocyanate 266:277 1,4-phenylene diisocyanate 252:277 1,4-phenylene diisocyanate (PDI) 252:283 An acylsemicarbazide-based porous organic polymer (POP) was facilely prepared by the polymerization of benzene-1,3,5-tricarbohydrazide (BTZ) and 1,4-phenylene diisocyanate (PDI). 29048831 1 87 theme 1,4-phenylene 252:264 arg1 PDI 280:282 PDI 280:282 PDI 280:282 An acylsemicarbazide-based porous organic polymer (POP) was facilely prepared by the polymerization of benzene-1,3,5-tricarbohydrazide (BTZ) and 1,4-phenylene diisocyanate (PDI). 29048831 5 88 theme desorption 1022:1031 arg1 ionization-time 1033:1047 matrix-assisted laser desorption ionization-time 1000:1047 matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis 1000:1099 The 19 typical N-linked glycopeptides were identified from 500 fmol tryptic digest of immunoglobulin G (IgG) from human serum by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis, meanwhile, 1919 unique glycopeptides with 1350 N-glycosylation sites from 605 different N-linked glycoproteins were identified from 100 μ g mouse liver tryptic digest by capillary liquid chromatography (cLC)-MS/MS analysis. 29048831 4 89 theme protein 819:825 arg1 digest 800:805 tryptic digest 792:805 tryptic digest of standard protein and complex biosamples in hydrophilic mode 792:868 Thus, POP-1 was tried to be used for glycopeptides enrichment from tryptic digest of standard protein and complex biosamples in hydrophilic mode. 29048831 5 90 theme capillary 1272:1280 arg1 cLC 1305:1307 cLC 1305:1307 cLC 1305:1307 The 19 typical N-linked glycopeptides were identified from 500 fmol tryptic digest of immunoglobulin G (IgG) from human serum by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis, meanwhile, 1919 unique glycopeptides with 1350 N-glycosylation sites from 605 different N-linked glycoproteins were identified from 100 μ g mouse liver tryptic digest by capillary liquid chromatography (cLC)-MS/MS analysis. 29048831 5 90 theme capillary 1272:1280 arg1 chromatography 1289:1302 capillary liquid chromatography 1272:1302 capillary liquid chromatography (cLC)-MS/MS analysis 1272:1323 The 19 typical N-linked glycopeptides were identified from 500 fmol tryptic digest of immunoglobulin G (IgG) from human serum by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis, meanwhile, 1919 unique glycopeptides with 1350 N-glycosylation sites from 605 different N-linked glycoproteins were identified from 100 μ g mouse liver tryptic digest by capillary liquid chromatography (cLC)-MS/MS analysis. 29048831 5 91 from serum 991:995 arg1 IgG 975:977 IgG 975:977 IgG 975:977 The 19 typical N-linked glycopeptides were identified from 500 fmol tryptic digest of immunoglobulin G (IgG) from human serum by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis, meanwhile, 1919 unique glycopeptides with 1350 N-glycosylation sites from 605 different N-linked glycoproteins were identified from 100 μ g mouse liver tryptic digest by capillary liquid chromatography (cLC)-MS/MS analysis. 29048831 5 91 from serum 991:995 arg1 digest 947:952 500 fmol tryptic digest 930:952 500 fmol tryptic digest of immunoglobulin G (IgG) from human serum 930:995 The 19 typical N-linked glycopeptides were identified from 500 fmol tryptic digest of immunoglobulin G (IgG) from human serum by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis, meanwhile, 1919 unique glycopeptides with 1350 N-glycosylation sites from 605 different N-linked glycoproteins were identified from 100 μ g mouse liver tryptic digest by capillary liquid chromatography (cLC)-MS/MS analysis. 29048831 5 91 from serum 991:995 arg1 G 972:972 immunoglobulin G 957:972 immunoglobulin G (IgG) from human serum 957:995 The 19 typical N-linked glycopeptides were identified from 500 fmol tryptic digest of immunoglobulin G (IgG) from human serum by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis, meanwhile, 1919 unique glycopeptides with 1350 N-glycosylation sites from 605 different N-linked glycoproteins were identified from 100 μ g mouse liver tryptic digest by capillary liquid chromatography (cLC)-MS/MS analysis. 29048831 5 92 theme liquid 1282:1287 arg1 cLC 1305:1307 cLC 1305:1307 cLC 1305:1307 The 19 typical N-linked glycopeptides were identified from 500 fmol tryptic digest of immunoglobulin G (IgG) from human serum by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis, meanwhile, 1919 unique glycopeptides with 1350 N-glycosylation sites from 605 different N-linked glycoproteins were identified from 100 μ g mouse liver tryptic digest by capillary liquid chromatography (cLC)-MS/MS analysis. 29048831 5 92 theme liquid 1282:1287 arg1 chromatography 1289:1302 capillary liquid chromatography 1272:1302 capillary liquid chromatography (cLC)-MS/MS analysis 1272:1323 The 19 typical N-linked glycopeptides were identified from 500 fmol tryptic digest of immunoglobulin G (IgG) from human serum by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis, meanwhile, 1919 unique glycopeptides with 1350 N-glycosylation sites from 605 different N-linked glycoproteins were identified from 100 μ g mouse liver tryptic digest by capillary liquid chromatography (cLC)-MS/MS analysis. 26237509 5 0 theme size 766:769 arg1 combination 751:761 a combination 749:761 a combination of size and conformational restriction 749:800 Crystal structures of four acceptor peptides in complex with Homo sapiens OGT suggest that a combination of size and conformational restriction defines sequence specificity in the -3 to +2 subsites. 26237509 6 1 theme OGT 919:921 arg1 repeats 908:914 the N-terminal TPR repeats 889:914 the N-terminal TPR repeats of OGT 889:921 This work reveals that although the N-terminal TPR repeats of OGT may have roles in substrate recognition, the sequence restriction imposed by the peptide-binding site makes a substantial contribution to O-GlcNAc site specificity. 26237509 1 2 theme intracellular 142:154 arg1 proteins 156:163 intracellular proteins 142:163 intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc), an essential and dynamic post-translational modification in metazoans 142:279 O-GlcNAc transferase (OGT) glycosylates a diverse range of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc), an essential and dynamic post-translational modification in metazoans. 26237509 6 3 theme O-GlcNAc 1061:1068 arg1 specificity 1075:1085 O-GlcNAc site specificity 1061:1085 O-GlcNAc site specificity 1061:1085 This work reveals that although the N-terminal TPR repeats of OGT may have roles in substrate recognition, the sequence restriction imposed by the peptide-binding site makes a substantial contribution to O-GlcNAc site specificity. 26237509 1 4 with proteins 156:163 arg1 N-acetylglucosamine 179:197 O-linked N-acetylglucosamine 170:197 O-linked N-acetylglucosamine (O-GlcNAc) 170:208 O-GlcNAc transferase (OGT) glycosylates a diverse range of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc), an essential and dynamic post-translational modification in metazoans. 26237509 1 4 with proteins 156:163 arg1 modification 255:266 an essential and dynamic post-translational modification 211:266 an essential and dynamic post-translational modification in metazoans 211:279 O-GlcNAc transferase (OGT) glycosylates a diverse range of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc), an essential and dynamic post-translational modification in metazoans. 26237509 1 4 with proteins 156:163 arg1 O-GlcNAc 200:207 O-GlcNAc 200:207 O-GlcNAc 200:207 O-GlcNAc transferase (OGT) glycosylates a diverse range of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc), an essential and dynamic post-translational modification in metazoans. 26237509 3 5 theme peptides 499:506 arg1 library 488:494 a library 486:494 a library of peptides 486:506 In this study, we describe the application of a high-throughput OGT assay to a library of peptides. 26237509 4 6 theme dissociation 571:582 arg1 MS 584:585 electron transfer dissociation MS 553:585 electron transfer dissociation MS 553:585 We mapped sites of O-GlcNAc modification by electron transfer dissociation MS and found that they correlate with previously detected O-GlcNAc sites. 26237509 5 7 from complex 706:712 arg1 structures 666:675 Crystal structures 658:675 Crystal structures of four acceptor peptides in complex with Homo sapiens OGT 658:734 Crystal structures of four acceptor peptides in complex with Homo sapiens OGT suggest that a combination of size and conformational restriction defines sequence specificity in the -3 to +2 subsites. 26237509 6 8 theme TPR 904:906 arg1 repeats 908:914 the N-terminal TPR repeats 889:914 the N-terminal TPR repeats of OGT 889:921 This work reveals that although the N-terminal TPR repeats of OGT may have roles in substrate recognition, the sequence restriction imposed by the peptide-binding site makes a substantial contribution to O-GlcNAc site specificity. 26237509 2 9 with proteins 324:331 arg1 O-GlcNAc 338:345 O-GlcNAc 338:345 O-GlcNAc 338:345 Although this enzyme modifies hundreds of proteins with O-GlcNAc, it is not understood how OGT achieves substrate specificity. 26237509 6 10 theme N-terminal 893:902 arg1 repeats 908:914 the N-terminal TPR repeats 889:914 the N-terminal TPR repeats of OGT 889:921 This work reveals that although the N-terminal TPR repeats of OGT may have roles in substrate recognition, the sequence restriction imposed by the peptide-binding site makes a substantial contribution to O-GlcNAc site specificity. 26237509 5 11 theme +2 844:845 arg1 subsites 847:854 the -3 to +2 subsites 834:854 the -3 to +2 subsites 834:854 Crystal structures of four acceptor peptides in complex with Homo sapiens OGT suggest that a combination of size and conformational restriction defines sequence specificity in the -3 to +2 subsites. 26237509 5 12 from specificity 819:829 arg1 subsites 847:854 the -3 to +2 subsites 834:854 the -3 to +2 subsites 834:854 Crystal structures of four acceptor peptides in complex with Homo sapiens OGT suggest that a combination of size and conformational restriction defines sequence specificity in the -3 to +2 subsites. 26237509 5 13 theme conformational 775:788 arg1 restriction 790:800 conformational restriction 775:800 conformational restriction 775:800 Crystal structures of four acceptor peptides in complex with Homo sapiens OGT suggest that a combination of size and conformational restriction defines sequence specificity in the -3 to +2 subsites. 26237509 1 14 theme O-linked 170:177 arg1 N-acetylglucosamine 179:197 O-linked N-acetylglucosamine 170:197 O-linked N-acetylglucosamine (O-GlcNAc) 170:208 O-GlcNAc transferase (OGT) glycosylates a diverse range of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc), an essential and dynamic post-translational modification in metazoans. 26237509 1 14 theme O-linked 170:177 arg1 modification 255:266 an essential and dynamic post-translational modification 211:266 an essential and dynamic post-translational modification in metazoans 211:279 O-GlcNAc transferase (OGT) glycosylates a diverse range of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc), an essential and dynamic post-translational modification in metazoans. 26237509 1 14 theme O-linked 170:177 arg1 O-GlcNAc 200:207 O-GlcNAc 200:207 O-GlcNAc 200:207 O-GlcNAc transferase (OGT) glycosylates a diverse range of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc), an essential and dynamic post-translational modification in metazoans. 26237509 0 15 theme active 4:9 arg1 site 11:14 The active site 0:14 The active site of O-GlcNAc transferase 0:38 The active site of O-GlcNAc transferase imposes constraints on substrate sequence. 26237509 0 15 theme active 4:9 arg1 transferase 28:38 O-GlcNAc transferase 19:38 O-GlcNAc transferase 19:38 The active site of O-GlcNAc transferase imposes constraints on substrate sequence. 26237509 1 16 theme O-GlcNAc 83:90 arg1 transferase 92:102 O-GlcNAc transferase 83:102 O-GlcNAc transferase (OGT) 83:108 O-GlcNAc transferase (OGT) glycosylates a diverse range of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc), an essential and dynamic post-translational modification in metazoans. 26237509 1 16 theme O-GlcNAc 83:90 arg1 OGT 105:107 OGT 105:107 OGT 105:107 O-GlcNAc transferase (OGT) glycosylates a diverse range of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc), an essential and dynamic post-translational modification in metazoans. 26237509 2 17 theme substrate 386:394 arg1 specificity 396:406 substrate specificity 386:406 substrate specificity 386:406 Although this enzyme modifies hundreds of proteins with O-GlcNAc, it is not understood how OGT achieves substrate specificity. 26237509 5 18 theme Homo 719:722 arg1 sapiens 724:730 Homo sapiens OGT 719:734 Homo sapiens OGT 719:734 Crystal structures of four acceptor peptides in complex with Homo sapiens OGT suggest that a combination of size and conformational restriction defines sequence specificity in the -3 to +2 subsites. 26237509 6 19 theme sequence 968:975 arg1 restriction 977:987 the sequence restriction 964:987 the sequence restriction imposed by the peptide-binding site 964:1023 This work reveals that although the N-terminal TPR repeats of OGT may have roles in substrate recognition, the sequence restriction imposed by the peptide-binding site makes a substantial contribution to O-GlcNAc site specificity. 26237509 1 20 link O-linked 170:177 arg1 N-acetylglucosamine 179:197 O-linked N-acetylglucosamine 170:197 O-linked N-acetylglucosamine (O-GlcNAc) 170:208 O-GlcNAc transferase (OGT) glycosylates a diverse range of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc), an essential and dynamic post-translational modification in metazoans. 26237509 1 20 link O-linked 170:177 arg1 modification 255:266 an essential and dynamic post-translational modification 211:266 an essential and dynamic post-translational modification in metazoans 211:279 O-GlcNAc transferase (OGT) glycosylates a diverse range of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc), an essential and dynamic post-translational modification in metazoans. 26237509 1 20 link O-linked 170:177 arg1 O-GlcNAc 200:207 O-GlcNAc 200:207 O-GlcNAc 200:207 O-GlcNAc transferase (OGT) glycosylates a diverse range of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc), an essential and dynamic post-translational modification in metazoans. 26237509 2 21 theme proteins 324:331 arg1 hundreds 312:319 hundreds 312:319 hundreds of proteins with O-GlcNAc 312:345 Although this enzyme modifies hundreds of proteins with O-GlcNAc, it is not understood how OGT achieves substrate specificity. 26237509 5 22 theme Crystal 658:664 arg1 structures 666:675 Crystal structures 658:675 Crystal structures of four acceptor peptides in complex with Homo sapiens OGT 658:734 Crystal structures of four acceptor peptides in complex with Homo sapiens OGT suggest that a combination of size and conformational restriction defines sequence specificity in the -3 to +2 subsites. 26237509 4 23 theme modification 537:548 arg1 sites 519:523 sites 519:523 sites of O-GlcNAc modification 519:548 We mapped sites of O-GlcNAc modification by electron transfer dissociation MS and found that they correlate with previously detected O-GlcNAc sites. 26237509 4 23 theme modification 537:548 arg1 modification 537:548 O-GlcNAc modification 528:548 O-GlcNAc modification 528:548 We mapped sites of O-GlcNAc modification by electron transfer dissociation MS and found that they correlate with previously detected O-GlcNAc sites. 26237509 1 24 gly glycosylates 110:121 arg1 range 133:137 a diverse range 123:137 a diverse range of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc), an essential and dynamic post-translational modification in metazoans 123:279 O-GlcNAc transferase (OGT) glycosylates a diverse range of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc), an essential and dynamic post-translational modification in metazoans. 26237509 3 25 theme high-throughput 457:471 arg1 assay 477:481 a high-throughput OGT assay 455:481 a high-throughput OGT assay 455:481 In this study, we describe the application of a high-throughput OGT assay to a library of peptides. 26237509 4 26 theme transfer 562:569 arg1 MS 584:585 electron transfer dissociation MS 553:585 electron transfer dissociation MS 553:585 We mapped sites of O-GlcNAc modification by electron transfer dissociation MS and found that they correlate with previously detected O-GlcNAc sites. 26237509 1 27 theme proteins 156:163 arg1 range 133:137 a diverse range 123:137 a diverse range of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc), an essential and dynamic post-translational modification in metazoans 123:279 O-GlcNAc transferase (OGT) glycosylates a diverse range of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc), an essential and dynamic post-translational modification in metazoans. 26237509 3 28 theme OGT 473:475 arg1 assay 477:481 a high-throughput OGT assay 455:481 a high-throughput OGT assay 455:481 In this study, we describe the application of a high-throughput OGT assay to a library of peptides. 26237509 0 29 theme transferase 28:38 arg1 site 11:14 The active site 0:14 The active site of O-GlcNAc transferase 0:38 The active site of O-GlcNAc transferase imposes constraints on substrate sequence. 26237509 0 29 theme transferase 28:38 arg1 transferase 28:38 O-GlcNAc transferase 19:38 O-GlcNAc transferase 19:38 The active site of O-GlcNAc transferase imposes constraints on substrate sequence. 26237509 4 30 theme electron 553:560 arg1 MS 584:585 electron transfer dissociation MS 553:585 electron transfer dissociation MS 553:585 We mapped sites of O-GlcNAc modification by electron transfer dissociation MS and found that they correlate with previously detected O-GlcNAc sites. 26237509 1 31 from modification 255:266 arg1 metazoans 271:279 metazoans 271:279 metazoans 271:279 O-GlcNAc transferase (OGT) glycosylates a diverse range of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc), an essential and dynamic post-translational modification in metazoans. 26237509 6 32 theme site 1070:1073 arg1 specificity 1075:1085 O-GlcNAc site specificity 1061:1085 O-GlcNAc site specificity 1061:1085 This work reveals that although the N-terminal TPR repeats of OGT may have roles in substrate recognition, the sequence restriction imposed by the peptide-binding site makes a substantial contribution to O-GlcNAc site specificity. 26237509 5 33 with complex 706:712 arg1 sapiens 724:730 Homo sapiens OGT 719:734 Homo sapiens OGT 719:734 Crystal structures of four acceptor peptides in complex with Homo sapiens OGT suggest that a combination of size and conformational restriction defines sequence specificity in the -3 to +2 subsites. 26237509 0 34 theme O-GlcNAc 19:26 arg1 transferase 28:38 O-GlcNAc transferase 19:38 O-GlcNAc transferase 19:38 The active site of O-GlcNAc transferase imposes constraints on substrate sequence. 26237509 5 35 from structures 666:675 arg1 complex 706:712 complex 706:712 complex with Homo sapiens OGT 706:734 Crystal structures of four acceptor peptides in complex with Homo sapiens OGT suggest that a combination of size and conformational restriction defines sequence specificity in the -3 to +2 subsites. 26237509 5 36 theme restriction 790:800 arg1 combination 751:761 a combination 749:761 a combination of size and conformational restriction 749:800 Crystal structures of four acceptor peptides in complex with Homo sapiens OGT suggest that a combination of size and conformational restriction defines sequence specificity in the -3 to +2 subsites. 26237509 4 37 theme O-GlcNAc 642:649 arg1 sites 651:655 previously detected O-GlcNAc sites 622:655 previously detected O-GlcNAc sites 622:655 We mapped sites of O-GlcNAc modification by electron transfer dissociation MS and found that they correlate with previously detected O-GlcNAc sites. 26237509 6 38 theme substrate 941:949 arg1 recognition 951:961 substrate recognition 941:961 substrate recognition 941:961 This work reveals that although the N-terminal TPR repeats of OGT may have roles in substrate recognition, the sequence restriction imposed by the peptide-binding site makes a substantial contribution to O-GlcNAc site specificity. 26237509 5 39 theme sequence 810:817 arg1 specificity 819:829 sequence specificity 810:829 sequence specificity in the -3 to +2 subsites 810:854 Crystal structures of four acceptor peptides in complex with Homo sapiens OGT suggest that a combination of size and conformational restriction defines sequence specificity in the -3 to +2 subsites. 26237509 4 40 theme O-GlcNAc 528:535 arg1 modification 537:548 O-GlcNAc modification 528:548 O-GlcNAc modification 528:548 We mapped sites of O-GlcNAc modification by electron transfer dissociation MS and found that they correlate with previously detected O-GlcNAc sites. 26237509 5 41 theme acceptor 685:692 arg1 peptides 694:701 four acceptor peptides 680:701 four acceptor peptides in complex with Homo sapiens OGT 680:734 Crystal structures of four acceptor peptides in complex with Homo sapiens OGT suggest that a combination of size and conformational restriction defines sequence specificity in the -3 to +2 subsites. 26237509 5 42 theme peptides 694:701 arg1 structures 666:675 Crystal structures 658:675 Crystal structures of four acceptor peptides in complex with Homo sapiens OGT 658:734 Crystal structures of four acceptor peptides in complex with Homo sapiens OGT suggest that a combination of size and conformational restriction defines sequence specificity in the -3 to +2 subsites. 26237509 6 43 contain have 927:930 arg2 roles 932:936 roles 932:936 roles 932:936 This work reveals that although the N-terminal TPR repeats of OGT may have roles in substrate recognition, the sequence restriction imposed by the peptide-binding site makes a substantial contribution to O-GlcNAc site specificity. 26237509 6 43 contain have 927:930 arg1 repeats 908:914 the N-terminal TPR repeats 889:914 the N-terminal TPR repeats of OGT 889:921 This work reveals that although the N-terminal TPR repeats of OGT may have roles in substrate recognition, the sequence restriction imposed by the peptide-binding site makes a substantial contribution to O-GlcNAc site specificity. 26237509 5 44 dep subsites 847:854 arg1 to 841:842 to 841:842 to 841:842 Crystal structures of four acceptor peptides in complex with Homo sapiens OGT suggest that a combination of size and conformational restriction defines sequence specificity in the -3 to +2 subsites. 26237509 3 45 theme assay 477:481 arg1 application 440:450 the application 436:450 the application of a high-throughput OGT assay to a library of peptides 436:506 In this study, we describe the application of a high-throughput OGT assay to a library of peptides. 26237509 1 46 theme essential 214:222 arg1 N-acetylglucosamine 179:197 O-linked N-acetylglucosamine 170:197 O-linked N-acetylglucosamine (O-GlcNAc) 170:208 O-GlcNAc transferase (OGT) glycosylates a diverse range of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc), an essential and dynamic post-translational modification in metazoans. 26237509 1 46 theme essential 214:222 arg1 modification 255:266 an essential and dynamic post-translational modification 211:266 an essential and dynamic post-translational modification in metazoans 211:279 O-GlcNAc transferase (OGT) glycosylates a diverse range of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc), an essential and dynamic post-translational modification in metazoans. 26237509 1 47 theme diverse 125:131 arg1 range 133:137 a diverse range 123:137 a diverse range of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc), an essential and dynamic post-translational modification in metazoans 123:279 O-GlcNAc transferase (OGT) glycosylates a diverse range of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc), an essential and dynamic post-translational modification in metazoans. 26237509 0 48 theme substrate 63:71 arg1 sequence 73:80 substrate sequence 63:80 substrate sequence 63:80 The active site of O-GlcNAc transferase imposes constraints on substrate sequence. 26237509 6 49 theme substantial 1033:1043 arg1 contribution 1045:1056 a substantial contribution 1031:1056 a substantial contribution to O-GlcNAc site specificity 1031:1085 This work reveals that although the N-terminal TPR repeats of OGT may have roles in substrate recognition, the sequence restriction imposed by the peptide-binding site makes a substantial contribution to O-GlcNAc site specificity. 26237509 4 50 theme detected 633:640 arg1 sites 651:655 previously detected O-GlcNAc sites 622:655 previously detected O-GlcNAc sites 622:655 We mapped sites of O-GlcNAc modification by electron transfer dissociation MS and found that they correlate with previously detected O-GlcNAc sites. 26237509 1 51 theme dynamic 228:234 arg1 N-acetylglucosamine 179:197 O-linked N-acetylglucosamine 170:197 O-linked N-acetylglucosamine (O-GlcNAc) 170:208 O-GlcNAc transferase (OGT) glycosylates a diverse range of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc), an essential and dynamic post-translational modification in metazoans. 26237509 1 51 theme dynamic 228:234 arg1 modification 255:266 an essential and dynamic post-translational modification 211:266 an essential and dynamic post-translational modification in metazoans 211:279 O-GlcNAc transferase (OGT) glycosylates a diverse range of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc), an essential and dynamic post-translational modification in metazoans. 26237509 5 52 dep sapiens 724:730 arg1 OGT 732:734 OGT 732:734 Homo sapiens OGT 719:734 Crystal structures of four acceptor peptides in complex with Homo sapiens OGT suggest that a combination of size and conformational restriction defines sequence specificity in the -3 to +2 subsites. 26237509 6 53 theme peptide-binding 1004:1018 arg1 site 1020:1023 the peptide-binding site 1000:1023 the peptide-binding site 1000:1023 This work reveals that although the N-terminal TPR repeats of OGT may have roles in substrate recognition, the sequence restriction imposed by the peptide-binding site makes a substantial contribution to O-GlcNAc site specificity. 26237509 5 54 from peptides 694:701 arg1 complex 706:712 complex 706:712 complex with Homo sapiens OGT 706:734 Crystal structures of four acceptor peptides in complex with Homo sapiens OGT suggest that a combination of size and conformational restriction defines sequence specificity in the -3 to +2 subsites. 26237509 1 55 theme post-translational 236:253 arg1 N-acetylglucosamine 179:197 O-linked N-acetylglucosamine 170:197 O-linked N-acetylglucosamine (O-GlcNAc) 170:208 O-GlcNAc transferase (OGT) glycosylates a diverse range of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc), an essential and dynamic post-translational modification in metazoans. 26237509 1 55 theme post-translational 236:253 arg1 modification 255:266 an essential and dynamic post-translational modification 211:266 an essential and dynamic post-translational modification in metazoans 211:279 O-GlcNAc transferase (OGT) glycosylates a diverse range of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc), an essential and dynamic post-translational modification in metazoans. 25567004 7 0 theme rational 1587:1594 arg1 strategy 1609:1616 a rational and feasible strategy 1585:1616 a rational and feasible strategy for the secretory expression of botulism or other toxin antigens 1585:1681 This approach provides a rational and feasible strategy for the secretory expression of botulism or other toxin antigens. 25567004 4 1 theme signal 944:949 arg1 pro-peptide 917:927 an unexpected pro-peptide 903:927 an unexpected pro-peptide of an α-factor signal and fortuitous N-linked glycosylation sites in the non-cleaved pro-peptide sequences, but not in the BHc sequences 903:1064 Unexpectedly, deglycosylated proBHc contained an unexpected pro-peptide of an α-factor signal and fortuitous N-linked glycosylation sites in the non-cleaved pro-peptide sequences, but not in the BHc sequences. 25567004 4 2 theme fortuitous 955:964 arg1 sites 989:993 fortuitous N-linked glycosylation sites 955:993 fortuitous N-linked glycosylation sites 955:993 Unexpectedly, deglycosylated proBHc contained an unexpected pro-peptide of an α-factor signal and fortuitous N-linked glycosylation sites in the non-cleaved pro-peptide sequences, but not in the BHc sequences. 25567004 1 3 theme Pichia 294:299 arg1 pastoris 301:308 Pichia pastoris 294:308 Pichia pastoris 294:308 The recombinant Hc proteins of botulinum neurotoxins and tetanus toxin are exclusively produced by intracellular heterologous expression in Pichia pastoris for use in subunit vaccines; the same Hc proteins produced by secreted heterologous expression are hyper-glycosylated and immunologically inert. 25567004 4 4 link N-linked 966:973 arg1 sites 989:993 fortuitous N-linked glycosylation sites 955:993 fortuitous N-linked glycosylation sites 955:993 Unexpectedly, deglycosylated proBHc contained an unexpected pro-peptide of an α-factor signal and fortuitous N-linked glycosylation sites in the non-cleaved pro-peptide sequences, but not in the BHc sequences. 25567004 3 5 theme hyper-glycosylated 752:769 arg1 BSG 785:787 BSG 785:787 BSG 785:787 Recombinant low-glycosylated secreted BHc products (BSK) were also immunologically inert, similar to hyper-glycosylated BHc products (BSG), although deglycosylation restored their immunological activities. 25567004 3 5 theme hyper-glycosylated 752:769 arg1 products 775:782 hyper-glycosylated BHc products 752:782 hyper-glycosylated BHc products (BSG) 752:788 Recombinant low-glycosylated secreted BHc products (BSK) were also immunologically inert, similar to hyper-glycosylated BHc products (BSG), although deglycosylation restored their immunological activities. 25567004 1 6 theme neurotoxins 195:205 arg1 proteins 173:180 The recombinant Hc proteins 154:180 The recombinant Hc proteins of botulinum neurotoxins and tetanus toxin 154:223 The recombinant Hc proteins of botulinum neurotoxins and tetanus toxin are exclusively produced by intracellular heterologous expression in Pichia pastoris for use in subunit vaccines; the same Hc proteins produced by secreted heterologous expression are hyper-glycosylated and immunologically inert. 25567004 4 7 theme non-cleaved 1002:1012 arg1 sequences 1026:1034 the non-cleaved pro-peptide sequences 998:1034 the non-cleaved pro-peptide sequences 998:1034 Unexpectedly, deglycosylated proBHc contained an unexpected pro-peptide of an α-factor signal and fortuitous N-linked glycosylation sites in the non-cleaved pro-peptide sequences, but not in the BHc sequences. 25567004 0 8 theme products 125:132 arg1 Hc 87:88 Hc 87:88 Hc of botulinum neurotoxin serotype B products expressed in yeast 87:151 Characterization and immunological activity of different forms of recombinant secreted Hc of botulinum neurotoxin serotype B products expressed in yeast. 25567004 1 9 theme tetanus 211:217 arg1 toxin 219:223 tetanus toxin 211:223 tetanus toxin 211:223 The recombinant Hc proteins of botulinum neurotoxins and tetanus toxin are exclusively produced by intracellular heterologous expression in Pichia pastoris for use in subunit vaccines; the same Hc proteins produced by secreted heterologous expression are hyper-glycosylated and immunologically inert. 25567004 1 10 from expression 280:289 arg1 pastoris 301:308 Pichia pastoris 294:308 Pichia pastoris 294:308 The recombinant Hc proteins of botulinum neurotoxins and tetanus toxin are exclusively produced by intracellular heterologous expression in Pichia pastoris for use in subunit vaccines; the same Hc proteins produced by secreted heterologous expression are hyper-glycosylated and immunologically inert. 25567004 4 11 theme glycosylation 975:987 arg1 sites 989:993 fortuitous N-linked glycosylation sites 955:993 fortuitous N-linked glycosylation sites 955:993 Unexpectedly, deglycosylated proBHc contained an unexpected pro-peptide of an α-factor signal and fortuitous N-linked glycosylation sites in the non-cleaved pro-peptide sequences, but not in the BHc sequences. 25567004 6 12 theme non-glycosylated 1394:1409 arg1 isoform 1424:1430 a non-glycosylated secreted BHc isoform 1392:1430 a non-glycosylated secreted BHc isoform 1392:1430 In summary, we conclude that a non-glycosylated secreted BHc isoform can be prepared in yeast by deleting the pro-peptide of the α-factor signal and mutating its single potential glycosylation site. 25567004 3 13 theme secreted 680:687 arg1 BSK 703:705 BSK 703:705 BSK 703:705 Recombinant low-glycosylated secreted BHc products (BSK) were also immunologically inert, similar to hyper-glycosylated BHc products (BSG), although deglycosylation restored their immunological activities. 25567004 3 13 theme secreted 680:687 arg1 products 693:700 Recombinant low-glycosylated secreted BHc products 651:700 Recombinant low-glycosylated secreted BHc products (BSK) 651:706 Recombinant low-glycosylated secreted BHc products (BSK) were also immunologically inert, similar to hyper-glycosylated BHc products (BSG), although deglycosylation restored their immunological activities. 25567004 4 14 theme BHc 1052:1054 arg1 sequences 1056:1064 the BHc sequences 1048:1064 the BHc sequences 1048:1064 Unexpectedly, deglycosylated proBHc contained an unexpected pro-peptide of an α-factor signal and fortuitous N-linked glycosylation sites in the non-cleaved pro-peptide sequences, but not in the BHc sequences. 25567004 0 15 theme recombinant 66:76 arg1 forms 57:61 different forms 47:61 different forms of recombinant 47:76 Characterization and immunological activity of different forms of recombinant secreted Hc of botulinum neurotoxin serotype B products expressed in yeast. 25567004 1 16 theme same 343:346 arg1 proteins 351:358 the same Hc proteins 339:358 the same Hc proteins produced by secreted heterologous expression 339:403 The recombinant Hc proteins of botulinum neurotoxins and tetanus toxin are exclusively produced by intracellular heterologous expression in Pichia pastoris for use in subunit vaccines; the same Hc proteins produced by secreted heterologous expression are hyper-glycosylated and immunologically inert. 25567004 1 16 theme same 343:346 arg1 hyper-glycosylated 409:426 hyper-glycosylated 409:426 hyper-glycosylated 409:426 The recombinant Hc proteins of botulinum neurotoxins and tetanus toxin are exclusively produced by intracellular heterologous expression in Pichia pastoris for use in subunit vaccines; the same Hc proteins produced by secreted heterologous expression are hyper-glycosylated and immunologically inert. 25567004 3 17 theme Recombinant 651:661 arg1 BSK 703:705 BSK 703:705 BSK 703:705 Recombinant low-glycosylated secreted BHc products (BSK) were also immunologically inert, similar to hyper-glycosylated BHc products (BSG), although deglycosylation restored their immunological activities. 25567004 3 17 theme Recombinant 651:661 arg1 products 693:700 Recombinant low-glycosylated secreted BHc products 651:700 Recombinant low-glycosylated secreted BHc products (BSK) 651:706 Recombinant low-glycosylated secreted BHc products (BSK) were also immunologically inert, similar to hyper-glycosylated BHc products (BSG), although deglycosylation restored their immunological activities. 25567004 4 18 gly glycosylation 975:987 arg2 sites 989:993 fortuitous N-linked glycosylation sites 955:993 fortuitous N-linked glycosylation sites 955:993 Unexpectedly, deglycosylated proBHc contained an unexpected pro-peptide of an α-factor signal and fortuitous N-linked glycosylation sites in the non-cleaved pro-peptide sequences, but not in the BHc sequences. 25567004 2 19 theme serotype 536:543 arg1 B 545:545 botulinum neurotoxin serotype B 515:545 botulinum neurotoxin serotype B (BHc) 515:551 Here, several different recombinant secreted Hc proteins of botulinum neurotoxin serotype B (BHc) were expressed in yeast and we characterized and assessed their immunological activity in detail. 25567004 2 19 theme serotype 536:543 arg1 BHc 548:550 BHc 548:550 BHc 548:550 Here, several different recombinant secreted Hc proteins of botulinum neurotoxin serotype B (BHc) were expressed in yeast and we characterized and assessed their immunological activity in detail. 25567004 4 20 contain contained 893:901 arg1 proBHc 886:891 deglycosylated proBHc 871:891 deglycosylated proBHc 871:891 Unexpectedly, deglycosylated proBHc contained an unexpected pro-peptide of an α-factor signal and fortuitous N-linked glycosylation sites in the non-cleaved pro-peptide sequences, but not in the BHc sequences. 25567004 4 20 contain contained 893:901 arg2 pro-peptide 917:927 an unexpected pro-peptide 903:927 an unexpected pro-peptide of an α-factor signal and fortuitous N-linked glycosylation sites in the non-cleaved pro-peptide sequences, but not in the BHc sequences 903:1064 Unexpectedly, deglycosylated proBHc contained an unexpected pro-peptide of an α-factor signal and fortuitous N-linked glycosylation sites in the non-cleaved pro-peptide sequences, but not in the BHc sequences. 25567004 6 21 gly glycosylation 1542:1554 arg2 site 1556:1559 its single potential glycosylation site 1521:1559 its single potential glycosylation site 1521:1559 In summary, we conclude that a non-glycosylated secreted BHc isoform can be prepared in yeast by deleting the pro-peptide of the α-factor signal and mutating its single potential glycosylation site. 25567004 1 22 theme Hc 170:171 arg1 proteins 173:180 The recombinant Hc proteins 154:180 The recombinant Hc proteins of botulinum neurotoxins and tetanus toxin 154:223 The recombinant Hc proteins of botulinum neurotoxins and tetanus toxin are exclusively produced by intracellular heterologous expression in Pichia pastoris for use in subunit vaccines; the same Hc proteins produced by secreted heterologous expression are hyper-glycosylated and immunologically inert. 25567004 7 23 theme toxin 1668:1672 arg1 antigens 1674:1681 other toxin antigens 1662:1681 other toxin antigens 1662:1681 This approach provides a rational and feasible strategy for the secretory expression of botulism or other toxin antigens. 25567004 0 24 theme botulinum 93:101 arg1 B 123:123 botulinum neurotoxin serotype B 93:123 botulinum neurotoxin serotype B products expressed in yeast 93:151 Characterization and immunological activity of different forms of recombinant secreted Hc of botulinum neurotoxin serotype B products expressed in yeast. 25567004 5 25 theme protective 1306:1315 arg1 immunity 1317:1324 effective protective immunity 1296:1324 effective protective immunity 1296:1324 Notably, a non-glycosylated secreted homogeneous BHc isoform (mBHc), which we successfully prepared after deleting the pro-peptide and removing its single potential glycosylation site, was immunologically active and could confer effective protective immunity, similarly to non-glycosylated rBHc. 25567004 1 26 theme heterologous 381:392 arg1 expression 394:403 secreted heterologous expression 372:403 secreted heterologous expression 372:403 The recombinant Hc proteins of botulinum neurotoxins and tetanus toxin are exclusively produced by intracellular heterologous expression in Pichia pastoris for use in subunit vaccines; the same Hc proteins produced by secreted heterologous expression are hyper-glycosylated and immunologically inert. 25567004 2 27 theme secreted 491:498 arg1 proteins 503:510 several different recombinant secreted Hc proteins 461:510 several different recombinant secreted Hc proteins of botulinum neurotoxin serotype B (BHc) 461:551 Here, several different recombinant secreted Hc proteins of botulinum neurotoxin serotype B (BHc) were expressed in yeast and we characterized and assessed their immunological activity in detail. 25567004 6 28 theme single 1525:1530 arg1 site 1556:1559 its single potential glycosylation site 1521:1559 its single potential glycosylation site 1521:1559 In summary, we conclude that a non-glycosylated secreted BHc isoform can be prepared in yeast by deleting the pro-peptide of the α-factor signal and mutating its single potential glycosylation site. 25567004 3 29 dep inert 734:738 arg1 similar 741:747 similar 741:747 similar 741:747 Recombinant low-glycosylated secreted BHc products (BSK) were also immunologically inert, similar to hyper-glycosylated BHc products (BSG), although deglycosylation restored their immunological activities. 25567004 2 30 theme different 469:477 arg1 proteins 503:510 several different recombinant secreted Hc proteins 461:510 several different recombinant secreted Hc proteins of botulinum neurotoxin serotype B (BHc) 461:551 Here, several different recombinant secreted Hc proteins of botulinum neurotoxin serotype B (BHc) were expressed in yeast and we characterized and assessed their immunological activity in detail. 25567004 0 31 theme immunological 21:33 arg1 activity 35:42 immunological activity 21:42 immunological activity 21:42 Characterization and immunological activity of different forms of recombinant secreted Hc of botulinum neurotoxin serotype B products expressed in yeast. 25567004 2 32 theme botulinum 515:523 arg1 B 545:545 botulinum neurotoxin serotype B 515:545 botulinum neurotoxin serotype B (BHc) 515:551 Here, several different recombinant secreted Hc proteins of botulinum neurotoxin serotype B (BHc) were expressed in yeast and we characterized and assessed their immunological activity in detail. 25567004 2 32 theme botulinum 515:523 arg1 BHc 548:550 BHc 548:550 BHc 548:550 Here, several different recombinant secreted Hc proteins of botulinum neurotoxin serotype B (BHc) were expressed in yeast and we characterized and assessed their immunological activity in detail. 25567004 3 33 gly hyper-glycosylated 752:769 arg1 BSG 785:787 BSG 785:787 BSG 785:787 Recombinant low-glycosylated secreted BHc products (BSK) were also immunologically inert, similar to hyper-glycosylated BHc products (BSG), although deglycosylation restored their immunological activities. 25567004 3 33 gly hyper-glycosylated 752:769 arg1 products 775:782 hyper-glycosylated BHc products 752:782 hyper-glycosylated BHc products (BSG) 752:788 Recombinant low-glycosylated secreted BHc products (BSK) were also immunologically inert, similar to hyper-glycosylated BHc products (BSG), although deglycosylation restored their immunological activities. 25567004 6 34 theme signal 1501:1506 arg1 pro-peptide 1473:1483 the pro-peptide 1469:1483 the pro-peptide of the α-factor signal 1469:1506 In summary, we conclude that a non-glycosylated secreted BHc isoform can be prepared in yeast by deleting the pro-peptide of the α-factor signal and mutating its single potential glycosylation site. 25567004 1 35 theme subunit 321:327 arg1 vaccines 329:336 subunit vaccines 321:336 subunit vaccines 321:336 The recombinant Hc proteins of botulinum neurotoxins and tetanus toxin are exclusively produced by intracellular heterologous expression in Pichia pastoris for use in subunit vaccines; the same Hc proteins produced by secreted heterologous expression are hyper-glycosylated and immunologically inert. 25567004 5 36 theme homogeneous 1104:1114 arg1 active 1272:1277 active 1272:1277 active 1272:1277 Notably, a non-glycosylated secreted homogeneous BHc isoform (mBHc), which we successfully prepared after deleting the pro-peptide and removing its single potential glycosylation site, was immunologically active and could confer effective protective immunity, similarly to non-glycosylated rBHc. 25567004 5 36 theme homogeneous 1104:1114 arg1 mBHc 1129:1132 mBHc 1129:1132 mBHc 1129:1132 Notably, a non-glycosylated secreted homogeneous BHc isoform (mBHc), which we successfully prepared after deleting the pro-peptide and removing its single potential glycosylation site, was immunologically active and could confer effective protective immunity, similarly to non-glycosylated rBHc. 25567004 5 36 theme homogeneous 1104:1114 arg1 isoform 1120:1126 a non-glycosylated secreted homogeneous BHc isoform 1076:1126 a non-glycosylated secreted homogeneous BHc isoform (mBHc) 1076:1133 Notably, a non-glycosylated secreted homogeneous BHc isoform (mBHc), which we successfully prepared after deleting the pro-peptide and removing its single potential glycosylation site, was immunologically active and could confer effective protective immunity, similarly to non-glycosylated rBHc. 25567004 5 37 gly non-glycosylated 1078:1093 arg1 active 1272:1277 active 1272:1277 active 1272:1277 Notably, a non-glycosylated secreted homogeneous BHc isoform (mBHc), which we successfully prepared after deleting the pro-peptide and removing its single potential glycosylation site, was immunologically active and could confer effective protective immunity, similarly to non-glycosylated rBHc. 25567004 5 37 gly non-glycosylated 1078:1093 arg1 mBHc 1129:1132 mBHc 1129:1132 mBHc 1129:1132 Notably, a non-glycosylated secreted homogeneous BHc isoform (mBHc), which we successfully prepared after deleting the pro-peptide and removing its single potential glycosylation site, was immunologically active and could confer effective protective immunity, similarly to non-glycosylated rBHc. 25567004 5 37 gly non-glycosylated 1078:1093 arg1 isoform 1120:1126 a non-glycosylated secreted homogeneous BHc isoform 1076:1126 a non-glycosylated secreted homogeneous BHc isoform (mBHc) 1076:1133 Notably, a non-glycosylated secreted homogeneous BHc isoform (mBHc), which we successfully prepared after deleting the pro-peptide and removing its single potential glycosylation site, was immunologically active and could confer effective protective immunity, similarly to non-glycosylated rBHc. 25567004 5 38 theme potential 1222:1230 arg1 site 1246:1249 its single potential glycosylation site 1211:1249 its single potential glycosylation site 1211:1249 Notably, a non-glycosylated secreted homogeneous BHc isoform (mBHc), which we successfully prepared after deleting the pro-peptide and removing its single potential glycosylation site, was immunologically active and could confer effective protective immunity, similarly to non-glycosylated rBHc. 25567004 0 39 theme forms 57:61 arg1 Characterization 0:15 Characterization 0:15 Characterization 0:15 Characterization and immunological activity of different forms of recombinant secreted Hc of botulinum neurotoxin serotype B products expressed in yeast. 25567004 0 39 theme forms 57:61 arg1 activity 35:42 immunological activity 21:42 immunological activity 21:42 Characterization and immunological activity of different forms of recombinant secreted Hc of botulinum neurotoxin serotype B products expressed in yeast. 25567004 5 40 gly non-glycosylated 1340:1355 arg1 rBHc 1357:1360 non-glycosylated rBHc 1340:1360 non-glycosylated rBHc 1340:1360 Notably, a non-glycosylated secreted homogeneous BHc isoform (mBHc), which we successfully prepared after deleting the pro-peptide and removing its single potential glycosylation site, was immunologically active and could confer effective protective immunity, similarly to non-glycosylated rBHc. 25567004 5 41 theme non-glycosylated 1078:1093 arg1 active 1272:1277 active 1272:1277 active 1272:1277 Notably, a non-glycosylated secreted homogeneous BHc isoform (mBHc), which we successfully prepared after deleting the pro-peptide and removing its single potential glycosylation site, was immunologically active and could confer effective protective immunity, similarly to non-glycosylated rBHc. 25567004 5 41 theme non-glycosylated 1078:1093 arg1 mBHc 1129:1132 mBHc 1129:1132 mBHc 1129:1132 Notably, a non-glycosylated secreted homogeneous BHc isoform (mBHc), which we successfully prepared after deleting the pro-peptide and removing its single potential glycosylation site, was immunologically active and could confer effective protective immunity, similarly to non-glycosylated rBHc. 25567004 5 41 theme non-glycosylated 1078:1093 arg1 isoform 1120:1126 a non-glycosylated secreted homogeneous BHc isoform 1076:1126 a non-glycosylated secreted homogeneous BHc isoform (mBHc) 1076:1133 Notably, a non-glycosylated secreted homogeneous BHc isoform (mBHc), which we successfully prepared after deleting the pro-peptide and removing its single potential glycosylation site, was immunologically active and could confer effective protective immunity, similarly to non-glycosylated rBHc. 25567004 1 42 theme heterologous 267:278 arg1 expression 280:289 intracellular heterologous expression 253:289 intracellular heterologous expression in Pichia pastoris for use in subunit vaccines 253:336 The recombinant Hc proteins of botulinum neurotoxins and tetanus toxin are exclusively produced by intracellular heterologous expression in Pichia pastoris for use in subunit vaccines; the same Hc proteins produced by secreted heterologous expression are hyper-glycosylated and immunologically inert. 25567004 4 43 theme α-factor 935:942 arg1 signal 944:949 an α-factor signal 932:949 an α-factor signal 932:949 Unexpectedly, deglycosylated proBHc contained an unexpected pro-peptide of an α-factor signal and fortuitous N-linked glycosylation sites in the non-cleaved pro-peptide sequences, but not in the BHc sequences. 25567004 6 44 theme glycosylation 1542:1554 arg1 site 1556:1559 its single potential glycosylation site 1521:1559 its single potential glycosylation site 1521:1559 In summary, we conclude that a non-glycosylated secreted BHc isoform can be prepared in yeast by deleting the pro-peptide of the α-factor signal and mutating its single potential glycosylation site. 25567004 5 45 theme effective 1296:1304 arg1 immunity 1317:1324 effective protective immunity 1296:1324 effective protective immunity 1296:1324 Notably, a non-glycosylated secreted homogeneous BHc isoform (mBHc), which we successfully prepared after deleting the pro-peptide and removing its single potential glycosylation site, was immunologically active and could confer effective protective immunity, similarly to non-glycosylated rBHc. 25567004 2 46 theme immunological 617:629 arg1 activity 631:638 their immunological activity 611:638 their immunological activity 611:638 Here, several different recombinant secreted Hc proteins of botulinum neurotoxin serotype B (BHc) were expressed in yeast and we characterized and assessed their immunological activity in detail. 25567004 1 47 from use 314:316 arg1 vaccines 329:336 subunit vaccines 321:336 subunit vaccines 321:336 The recombinant Hc proteins of botulinum neurotoxins and tetanus toxin are exclusively produced by intracellular heterologous expression in Pichia pastoris for use in subunit vaccines; the same Hc proteins produced by secreted heterologous expression are hyper-glycosylated and immunologically inert. 25567004 6 48 gly non-glycosylated 1394:1409 arg1 isoform 1424:1430 a non-glycosylated secreted BHc isoform 1392:1430 a non-glycosylated secreted BHc isoform 1392:1430 In summary, we conclude that a non-glycosylated secreted BHc isoform can be prepared in yeast by deleting the pro-peptide of the α-factor signal and mutating its single potential glycosylation site. 25567004 4 49 theme unexpected 906:915 arg1 pro-peptide 917:927 an unexpected pro-peptide 903:927 an unexpected pro-peptide of an α-factor signal and fortuitous N-linked glycosylation sites in the non-cleaved pro-peptide sequences, but not in the BHc sequences 903:1064 Unexpectedly, deglycosylated proBHc contained an unexpected pro-peptide of an α-factor signal and fortuitous N-linked glycosylation sites in the non-cleaved pro-peptide sequences, but not in the BHc sequences. 25567004 3 50 gly low-glycosylated 663:678 arg1 BSK 703:705 BSK 703:705 BSK 703:705 Recombinant low-glycosylated secreted BHc products (BSK) were also immunologically inert, similar to hyper-glycosylated BHc products (BSG), although deglycosylation restored their immunological activities. 25567004 3 50 gly low-glycosylated 663:678 arg1 products 693:700 Recombinant low-glycosylated secreted BHc products 651:700 Recombinant low-glycosylated secreted BHc products (BSK) 651:706 Recombinant low-glycosylated secreted BHc products (BSK) were also immunologically inert, similar to hyper-glycosylated BHc products (BSG), although deglycosylation restored their immunological activities. 25567004 3 51 theme BHc 771:773 arg1 BSG 785:787 BSG 785:787 BSG 785:787 Recombinant low-glycosylated secreted BHc products (BSK) were also immunologically inert, similar to hyper-glycosylated BHc products (BSG), although deglycosylation restored their immunological activities. 25567004 3 51 theme BHc 771:773 arg1 products 775:782 hyper-glycosylated BHc products 752:782 hyper-glycosylated BHc products (BSG) 752:788 Recombinant low-glycosylated secreted BHc products (BSK) were also immunologically inert, similar to hyper-glycosylated BHc products (BSG), although deglycosylation restored their immunological activities. 25567004 1 52 theme botulinum 185:193 arg1 neurotoxins 195:205 botulinum neurotoxins 185:205 botulinum neurotoxins 185:205 The recombinant Hc proteins of botulinum neurotoxins and tetanus toxin are exclusively produced by intracellular heterologous expression in Pichia pastoris for use in subunit vaccines; the same Hc proteins produced by secreted heterologous expression are hyper-glycosylated and immunologically inert. 25567004 1 53 theme toxin 219:223 arg1 proteins 173:180 The recombinant Hc proteins 154:180 The recombinant Hc proteins of botulinum neurotoxins and tetanus toxin 154:223 The recombinant Hc proteins of botulinum neurotoxins and tetanus toxin are exclusively produced by intracellular heterologous expression in Pichia pastoris for use in subunit vaccines; the same Hc proteins produced by secreted heterologous expression are hyper-glycosylated and immunologically inert. 25567004 4 54 theme pro-peptide 1014:1024 arg1 sequences 1026:1034 the non-cleaved pro-peptide sequences 998:1034 the non-cleaved pro-peptide sequences 998:1034 Unexpectedly, deglycosylated proBHc contained an unexpected pro-peptide of an α-factor signal and fortuitous N-linked glycosylation sites in the non-cleaved pro-peptide sequences, but not in the BHc sequences. 25567004 3 55 theme immunological 831:843 arg1 activities 845:854 their immunological activities 825:854 their immunological activities 825:854 Recombinant low-glycosylated secreted BHc products (BSK) were also immunologically inert, similar to hyper-glycosylated BHc products (BSG), although deglycosylation restored their immunological activities. 25567004 6 56 theme secreted 1411:1418 arg1 isoform 1424:1430 a non-glycosylated secreted BHc isoform 1392:1430 a non-glycosylated secreted BHc isoform 1392:1430 In summary, we conclude that a non-glycosylated secreted BHc isoform can be prepared in yeast by deleting the pro-peptide of the α-factor signal and mutating its single potential glycosylation site. 25567004 4 57 theme N-linked 966:973 arg1 sites 989:993 fortuitous N-linked glycosylation sites 955:993 fortuitous N-linked glycosylation sites 955:993 Unexpectedly, deglycosylated proBHc contained an unexpected pro-peptide of an α-factor signal and fortuitous N-linked glycosylation sites in the non-cleaved pro-peptide sequences, but not in the BHc sequences. 25567004 3 58 theme low-glycosylated 663:678 arg1 BSK 703:705 BSK 703:705 BSK 703:705 Recombinant low-glycosylated secreted BHc products (BSK) were also immunologically inert, similar to hyper-glycosylated BHc products (BSG), although deglycosylation restored their immunological activities. 25567004 3 58 theme low-glycosylated 663:678 arg1 products 693:700 Recombinant low-glycosylated secreted BHc products 651:700 Recombinant low-glycosylated secreted BHc products (BSK) 651:706 Recombinant low-glycosylated secreted BHc products (BSK) were also immunologically inert, similar to hyper-glycosylated BHc products (BSG), although deglycosylation restored their immunological activities. 25567004 4 59 theme sites 989:993 arg1 pro-peptide 917:927 an unexpected pro-peptide 903:927 an unexpected pro-peptide of an α-factor signal and fortuitous N-linked glycosylation sites in the non-cleaved pro-peptide sequences, but not in the BHc sequences 903:1064 Unexpectedly, deglycosylated proBHc contained an unexpected pro-peptide of an α-factor signal and fortuitous N-linked glycosylation sites in the non-cleaved pro-peptide sequences, but not in the BHc sequences. 25567004 5 60 gly glycosylation 1232:1244 arg2 site 1246:1249 its single potential glycosylation site 1211:1249 its single potential glycosylation site 1211:1249 Notably, a non-glycosylated secreted homogeneous BHc isoform (mBHc), which we successfully prepared after deleting the pro-peptide and removing its single potential glycosylation site, was immunologically active and could confer effective protective immunity, similarly to non-glycosylated rBHc. 25567004 7 61 theme antigens 1674:1681 arg1 expression 1636:1645 the secretory expression 1622:1645 the secretory expression of botulism or other toxin antigens 1622:1681 This approach provides a rational and feasible strategy for the secretory expression of botulism or other toxin antigens. 25567004 2 62 theme B 545:545 arg1 proteins 503:510 several different recombinant secreted Hc proteins 461:510 several different recombinant secreted Hc proteins of botulinum neurotoxin serotype B (BHc) 461:551 Here, several different recombinant secreted Hc proteins of botulinum neurotoxin serotype B (BHc) were expressed in yeast and we characterized and assessed their immunological activity in detail. 25567004 5 63 theme non-glycosylated 1340:1355 arg1 rBHc 1357:1360 non-glycosylated rBHc 1340:1360 non-glycosylated rBHc 1340:1360 Notably, a non-glycosylated secreted homogeneous BHc isoform (mBHc), which we successfully prepared after deleting the pro-peptide and removing its single potential glycosylation site, was immunologically active and could confer effective protective immunity, similarly to non-glycosylated rBHc. 25567004 1 64 theme Hc 348:349 arg1 proteins 351:358 the same Hc proteins 339:358 the same Hc proteins produced by secreted heterologous expression 339:403 The recombinant Hc proteins of botulinum neurotoxins and tetanus toxin are exclusively produced by intracellular heterologous expression in Pichia pastoris for use in subunit vaccines; the same Hc proteins produced by secreted heterologous expression are hyper-glycosylated and immunologically inert. 25567004 1 64 theme Hc 348:349 arg1 hyper-glycosylated 409:426 hyper-glycosylated 409:426 hyper-glycosylated 409:426 The recombinant Hc proteins of botulinum neurotoxins and tetanus toxin are exclusively produced by intracellular heterologous expression in Pichia pastoris for use in subunit vaccines; the same Hc proteins produced by secreted heterologous expression are hyper-glycosylated and immunologically inert. 25567004 1 65 theme recombinant 158:168 arg1 proteins 173:180 The recombinant Hc proteins 154:180 The recombinant Hc proteins of botulinum neurotoxins and tetanus toxin 154:223 The recombinant Hc proteins of botulinum neurotoxins and tetanus toxin are exclusively produced by intracellular heterologous expression in Pichia pastoris for use in subunit vaccines; the same Hc proteins produced by secreted heterologous expression are hyper-glycosylated and immunologically inert. 25567004 7 66 theme other 1662:1666 arg1 antigens 1674:1681 other toxin antigens 1662:1681 other toxin antigens 1662:1681 This approach provides a rational and feasible strategy for the secretory expression of botulism or other toxin antigens. 25567004 2 67 theme neurotoxin 525:534 arg1 B 545:545 botulinum neurotoxin serotype B 515:545 botulinum neurotoxin serotype B (BHc) 515:551 Here, several different recombinant secreted Hc proteins of botulinum neurotoxin serotype B (BHc) were expressed in yeast and we characterized and assessed their immunological activity in detail. 25567004 2 67 theme neurotoxin 525:534 arg1 BHc 548:550 BHc 548:550 BHc 548:550 Here, several different recombinant secreted Hc proteins of botulinum neurotoxin serotype B (BHc) were expressed in yeast and we characterized and assessed their immunological activity in detail. 25567004 0 68 theme neurotoxin 103:112 arg1 B 123:123 botulinum neurotoxin serotype B 93:123 botulinum neurotoxin serotype B products expressed in yeast 93:151 Characterization and immunological activity of different forms of recombinant secreted Hc of botulinum neurotoxin serotype B products expressed in yeast. 25567004 5 69 theme single 1215:1220 arg1 site 1246:1249 its single potential glycosylation site 1211:1249 its single potential glycosylation site 1211:1249 Notably, a non-glycosylated secreted homogeneous BHc isoform (mBHc), which we successfully prepared after deleting the pro-peptide and removing its single potential glycosylation site, was immunologically active and could confer effective protective immunity, similarly to non-glycosylated rBHc. 25567004 7 70 theme botulism 1650:1657 arg1 expression 1636:1645 the secretory expression 1622:1645 the secretory expression of botulism or other toxin antigens 1622:1681 This approach provides a rational and feasible strategy for the secretory expression of botulism or other toxin antigens. 25567004 0 71 theme B 123:123 arg1 products 125:132 botulinum neurotoxin serotype B products 93:132 botulinum neurotoxin serotype B products expressed in yeast 93:151 Characterization and immunological activity of different forms of recombinant secreted Hc of botulinum neurotoxin serotype B products expressed in yeast. 25567004 1 72 theme secreted 372:379 arg1 expression 394:403 secreted heterologous expression 372:403 secreted heterologous expression 372:403 The recombinant Hc proteins of botulinum neurotoxins and tetanus toxin are exclusively produced by intracellular heterologous expression in Pichia pastoris for use in subunit vaccines; the same Hc proteins produced by secreted heterologous expression are hyper-glycosylated and immunologically inert. 25567004 6 73 theme potential 1532:1540 arg1 site 1556:1559 its single potential glycosylation site 1521:1559 its single potential glycosylation site 1521:1559 In summary, we conclude that a non-glycosylated secreted BHc isoform can be prepared in yeast by deleting the pro-peptide of the α-factor signal and mutating its single potential glycosylation site. 25567004 2 74 theme recombinant 479:489 arg1 proteins 503:510 several different recombinant secreted Hc proteins 461:510 several different recombinant secreted Hc proteins of botulinum neurotoxin serotype B (BHc) 461:551 Here, several different recombinant secreted Hc proteins of botulinum neurotoxin serotype B (BHc) were expressed in yeast and we characterized and assessed their immunological activity in detail. 25567004 2 75 theme several 461:467 arg1 proteins 503:510 several different recombinant secreted Hc proteins 461:510 several different recombinant secreted Hc proteins of botulinum neurotoxin serotype B (BHc) 461:551 Here, several different recombinant secreted Hc proteins of botulinum neurotoxin serotype B (BHc) were expressed in yeast and we characterized and assessed their immunological activity in detail. 25567004 0 76 theme different 47:55 arg1 forms 57:61 different forms 47:61 different forms of recombinant 47:76 Characterization and immunological activity of different forms of recombinant secreted Hc of botulinum neurotoxin serotype B products expressed in yeast. 25567004 5 77 theme secreted 1095:1102 arg1 active 1272:1277 active 1272:1277 active 1272:1277 Notably, a non-glycosylated secreted homogeneous BHc isoform (mBHc), which we successfully prepared after deleting the pro-peptide and removing its single potential glycosylation site, was immunologically active and could confer effective protective immunity, similarly to non-glycosylated rBHc. 25567004 5 77 theme secreted 1095:1102 arg1 mBHc 1129:1132 mBHc 1129:1132 mBHc 1129:1132 Notably, a non-glycosylated secreted homogeneous BHc isoform (mBHc), which we successfully prepared after deleting the pro-peptide and removing its single potential glycosylation site, was immunologically active and could confer effective protective immunity, similarly to non-glycosylated rBHc. 25567004 5 77 theme secreted 1095:1102 arg1 isoform 1120:1126 a non-glycosylated secreted homogeneous BHc isoform 1076:1126 a non-glycosylated secreted homogeneous BHc isoform (mBHc) 1076:1133 Notably, a non-glycosylated secreted homogeneous BHc isoform (mBHc), which we successfully prepared after deleting the pro-peptide and removing its single potential glycosylation site, was immunologically active and could confer effective protective immunity, similarly to non-glycosylated rBHc. 25567004 3 78 theme BHc 689:691 arg1 BSK 703:705 BSK 703:705 BSK 703:705 Recombinant low-glycosylated secreted BHc products (BSK) were also immunologically inert, similar to hyper-glycosylated BHc products (BSG), although deglycosylation restored their immunological activities. 25567004 3 78 theme BHc 689:691 arg1 products 693:700 Recombinant low-glycosylated secreted BHc products 651:700 Recombinant low-glycosylated secreted BHc products (BSK) 651:706 Recombinant low-glycosylated secreted BHc products (BSK) were also immunologically inert, similar to hyper-glycosylated BHc products (BSG), although deglycosylation restored their immunological activities. 25567004 4 79 theme deglycosylated 871:884 arg1 proBHc 886:891 deglycosylated proBHc 871:891 deglycosylated proBHc 871:891 Unexpectedly, deglycosylated proBHc contained an unexpected pro-peptide of an α-factor signal and fortuitous N-linked glycosylation sites in the non-cleaved pro-peptide sequences, but not in the BHc sequences. 25567004 0 80 theme serotype 114:121 arg1 B 123:123 botulinum neurotoxin serotype B 93:123 botulinum neurotoxin serotype B products expressed in yeast 93:151 Characterization and immunological activity of different forms of recombinant secreted Hc of botulinum neurotoxin serotype B products expressed in yeast. 25567004 6 81 theme α-factor 1492:1499 arg1 signal 1501:1506 the α-factor signal 1488:1506 the α-factor signal 1488:1506 In summary, we conclude that a non-glycosylated secreted BHc isoform can be prepared in yeast by deleting the pro-peptide of the α-factor signal and mutating its single potential glycosylation site. 25567004 5 82 theme glycosylation 1232:1244 arg1 site 1246:1249 its single potential glycosylation site 1211:1249 its single potential glycosylation site 1211:1249 Notably, a non-glycosylated secreted homogeneous BHc isoform (mBHc), which we successfully prepared after deleting the pro-peptide and removing its single potential glycosylation site, was immunologically active and could confer effective protective immunity, similarly to non-glycosylated rBHc. 25567004 7 83 theme secretory 1626:1634 arg1 expression 1636:1645 the secretory expression 1622:1645 the secretory expression of botulism or other toxin antigens 1622:1681 This approach provides a rational and feasible strategy for the secretory expression of botulism or other toxin antigens. 25567004 5 84 theme BHc 1116:1118 arg1 active 1272:1277 active 1272:1277 active 1272:1277 Notably, a non-glycosylated secreted homogeneous BHc isoform (mBHc), which we successfully prepared after deleting the pro-peptide and removing its single potential glycosylation site, was immunologically active and could confer effective protective immunity, similarly to non-glycosylated rBHc. 25567004 5 84 theme BHc 1116:1118 arg1 mBHc 1129:1132 mBHc 1129:1132 mBHc 1129:1132 Notably, a non-glycosylated secreted homogeneous BHc isoform (mBHc), which we successfully prepared after deleting the pro-peptide and removing its single potential glycosylation site, was immunologically active and could confer effective protective immunity, similarly to non-glycosylated rBHc. 25567004 5 84 theme BHc 1116:1118 arg1 isoform 1120:1126 a non-glycosylated secreted homogeneous BHc isoform 1076:1126 a non-glycosylated secreted homogeneous BHc isoform (mBHc) 1076:1133 Notably, a non-glycosylated secreted homogeneous BHc isoform (mBHc), which we successfully prepared after deleting the pro-peptide and removing its single potential glycosylation site, was immunologically active and could confer effective protective immunity, similarly to non-glycosylated rBHc. 25567004 4 85 from pro-peptide 917:927 arg1 sequences 1056:1064 the BHc sequences 1048:1064 the BHc sequences 1048:1064 Unexpectedly, deglycosylated proBHc contained an unexpected pro-peptide of an α-factor signal and fortuitous N-linked glycosylation sites in the non-cleaved pro-peptide sequences, but not in the BHc sequences. 25567004 4 85 from pro-peptide 917:927 arg1 sequences 1026:1034 the non-cleaved pro-peptide sequences 998:1034 the non-cleaved pro-peptide sequences 998:1034 Unexpectedly, deglycosylated proBHc contained an unexpected pro-peptide of an α-factor signal and fortuitous N-linked glycosylation sites in the non-cleaved pro-peptide sequences, but not in the BHc sequences. 25567004 2 86 theme Hc 500:501 arg1 proteins 503:510 several different recombinant secreted Hc proteins 461:510 several different recombinant secreted Hc proteins of botulinum neurotoxin serotype B (BHc) 461:551 Here, several different recombinant secreted Hc proteins of botulinum neurotoxin serotype B (BHc) were expressed in yeast and we characterized and assessed their immunological activity in detail. 25567004 1 87 gly hyper-glycosylated 409:426 arg1 proteins 351:358 the same Hc proteins 339:358 the same Hc proteins produced by secreted heterologous expression 339:403 The recombinant Hc proteins of botulinum neurotoxins and tetanus toxin are exclusively produced by intracellular heterologous expression in Pichia pastoris for use in subunit vaccines; the same Hc proteins produced by secreted heterologous expression are hyper-glycosylated and immunologically inert. 25567004 1 87 gly hyper-glycosylated 409:426 arg1 hyper-glycosylated 409:426 hyper-glycosylated 409:426 hyper-glycosylated 409:426 The recombinant Hc proteins of botulinum neurotoxins and tetanus toxin are exclusively produced by intracellular heterologous expression in Pichia pastoris for use in subunit vaccines; the same Hc proteins produced by secreted heterologous expression are hyper-glycosylated and immunologically inert. 25567004 6 88 theme BHc 1420:1422 arg1 isoform 1424:1430 a non-glycosylated secreted BHc isoform 1392:1430 a non-glycosylated secreted BHc isoform 1392:1430 In summary, we conclude that a non-glycosylated secreted BHc isoform can be prepared in yeast by deleting the pro-peptide of the α-factor signal and mutating its single potential glycosylation site. 25567004 7 89 theme feasible 1600:1607 arg1 strategy 1609:1616 a rational and feasible strategy 1585:1616 a rational and feasible strategy for the secretory expression of botulism or other toxin antigens 1585:1681 This approach provides a rational and feasible strategy for the secretory expression of botulism or other toxin antigens. 25567004 4 90 gly deglycosylated 871:884 arg1 proBHc 886:891 deglycosylated proBHc 871:891 deglycosylated proBHc 871:891 Unexpectedly, deglycosylated proBHc contained an unexpected pro-peptide of an α-factor signal and fortuitous N-linked glycosylation sites in the non-cleaved pro-peptide sequences, but not in the BHc sequences. 25567004 1 91 theme intracellular 253:265 arg1 expression 280:289 intracellular heterologous expression 253:289 intracellular heterologous expression in Pichia pastoris for use in subunit vaccines 253:336 The recombinant Hc proteins of botulinum neurotoxins and tetanus toxin are exclusively produced by intracellular heterologous expression in Pichia pastoris for use in subunit vaccines; the same Hc proteins produced by secreted heterologous expression are hyper-glycosylated and immunologically inert. 28049584 0 0 theme glycopeptides 97:109 arg1 enrichment 74:83 the selective enrichment 60:83 the selective enrichment of N-linked glycopeptides 60:109 Synthesis of magnetic zwitterionic-hydrophilic material for the selective enrichment of N-linked glycopeptides. 28049584 5 1 theme @ 818:818 arg1 Au-l-cys 824:831 the prepared Fe3O4@PGMA@Au-l-cys 800:831 the prepared Fe3O4@PGMA@Au-l-cys 800:831 Besides, the prepared Fe3O4@PGMA@Au-l-cys showed high detection sensitivity (5 fmol IgG digest), approving enrichment capacity (75mgg-1), satisfactory enrichment recovery (89.8%), and great performance in the analysis and profiling of low-abundance N-linked glycopeptides. 28049584 5 2 theme fmol 870:873 arg1 digest 879:884 5 fmol IgG digest 868:884 5 fmol IgG digest 868:884 Besides, the prepared Fe3O4@PGMA@Au-l-cys showed high detection sensitivity (5 fmol IgG digest), approving enrichment capacity (75mgg-1), satisfactory enrichment recovery (89.8%), and great performance in the analysis and profiling of low-abundance N-linked glycopeptides. 28049584 5 2 theme fmol 870:873 arg1 sensitivity 855:865 high detection sensitivity 840:865 high detection sensitivity (5 fmol IgG digest) 840:885 Besides, the prepared Fe3O4@PGMA@Au-l-cys showed high detection sensitivity (5 fmol IgG digest), approving enrichment capacity (75mgg-1), satisfactory enrichment recovery (89.8%), and great performance in the analysis and profiling of low-abundance N-linked glycopeptides. 28049584 1 3 theme human 179:183 arg1 diseases 185:192 human diseases 179:192 human diseases 179:192 In consideration of the close connection between glycopeptides and human diseases, the efficient method to separate and enrich glycopeptides from complex biological samples is urgently required. 28049584 0 4 theme N-linked 88:95 arg1 glycopeptides 97:109 N-linked glycopeptides 88:109 N-linked glycopeptides 88:109 Synthesis of magnetic zwitterionic-hydrophilic material for the selective enrichment of N-linked glycopeptides. 28049584 5 5 theme @ 823:823 arg1 Au-l-cys 824:831 the prepared Fe3O4@PGMA@Au-l-cys 800:831 the prepared Fe3O4@PGMA@Au-l-cys 800:831 Besides, the prepared Fe3O4@PGMA@Au-l-cys showed high detection sensitivity (5 fmol IgG digest), approving enrichment capacity (75mgg-1), satisfactory enrichment recovery (89.8%), and great performance in the analysis and profiling of low-abundance N-linked glycopeptides. 28049584 6 6 theme sample 1321:1326 arg1 analyses 1294:1301 three replicate analyses 1278:1301 three replicate analyses of a 75μg protein sample extracted from mouse liver 1278:1353 Furthermore, the prepared material was employed in the enrichment of glycopeptides in intricate biological samples, and 774 unique N-glycosylation sites from 411 N-glycosylated proteins were reliably identified in three replicate analyses of a 75μg protein sample extracted from mouse liver, suggesting wide application prospect in glycoproteomics. 28049584 6 7 theme 75μg 1308:1311 arg1 sample 1321:1326 a 75μg protein sample 1306:1326 a 75μg protein sample extracted from mouse liver 1306:1353 Furthermore, the prepared material was employed in the enrichment of glycopeptides in intricate biological samples, and 774 unique N-glycosylation sites from 411 N-glycosylated proteins were reliably identified in three replicate analyses of a 75μg protein sample extracted from mouse liver, suggesting wide application prospect in glycoproteomics. 28049584 6 8 from enrichment 1119:1128 arg1 samples 1171:1177 intricate biological samples 1150:1177 intricate biological samples 1150:1177 Furthermore, the prepared material was employed in the enrichment of glycopeptides in intricate biological samples, and 774 unique N-glycosylation sites from 411 N-glycosylated proteins were reliably identified in three replicate analyses of a 75μg protein sample extracted from mouse liver, suggesting wide application prospect in glycoproteomics. 28049584 6 9 theme protein 1313:1319 arg1 sample 1321:1326 a 75μg protein sample 1306:1326 a 75μg protein sample extracted from mouse liver 1306:1353 Furthermore, the prepared material was employed in the enrichment of glycopeptides in intricate biological samples, and 774 unique N-glycosylation sites from 411 N-glycosylated proteins were reliably identified in three replicate analyses of a 75μg protein sample extracted from mouse liver, suggesting wide application prospect in glycoproteomics. 28049584 1 10 gly glycopeptides 239:251 arg2 glycopeptides 239:251 separate and enrich glycopeptides 219:251 separate and enrich glycopeptides from complex biological samples 219:283 In consideration of the close connection between glycopeptides and human diseases, the efficient method to separate and enrich glycopeptides from complex biological samples is urgently required. 28049584 1 10 gly glycopeptides 239:251 arg1 samples 277:283 complex biological samples 258:283 complex biological samples 258:283 In consideration of the close connection between glycopeptides and human diseases, the efficient method to separate and enrich glycopeptides from complex biological samples is urgently required. 28049584 6 11 from proteins 1241:1248 arg1 sites 1211:1215 774 unique N-glycosylation sites 1184:1215 774 unique N-glycosylation sites from 411 N-glycosylated proteins 1184:1248 Furthermore, the prepared material was employed in the enrichment of glycopeptides in intricate biological samples, and 774 unique N-glycosylation sites from 411 N-glycosylated proteins were reliably identified in three replicate analyses of a 75μg protein sample extracted from mouse liver, suggesting wide application prospect in glycoproteomics. 28049584 3 12 mod modified 670:677 arg3 groups 697:702 zwitterionic groups 684:702 zwitterionic groups 684:702 The Fe3O4 particles were covered with a thick layer of polymer by one-step reflux-precipitation polymerization (RPP), subsequently decorated by Au nanoparticles (Au NPs) through in situ reduction and finally modified with zwitterionic groups. 28049584 3 12 mod modified 670:677 arg1 particles 472:480 The Fe3O4 particles 462:480 The Fe3O4 particles 462:480 The Fe3O4 particles were covered with a thick layer of polymer by one-step reflux-precipitation polymerization (RPP), subsequently decorated by Au nanoparticles (Au NPs) through in situ reduction and finally modified with zwitterionic groups. 28049584 2 13 from analysis 414:421 arg1 samples 453:459 complex samples 445:459 complex samples 445:459 In the work, we developed a magnetic zwitterionic-hydrophilic material for highly effective separation and analysis of glycopeptides from complex samples. 28049584 2 14 theme effective 389:397 arg1 separation 399:408 highly effective separation 382:408 highly effective separation 382:408 In the work, we developed a magnetic zwitterionic-hydrophilic material for highly effective separation and analysis of glycopeptides from complex samples. 28049584 3 15 theme polymer 517:523 arg1 layer 508:512 a thick layer 500:512 a thick layer of polymer 500:523 The Fe3O4 particles were covered with a thick layer of polymer by one-step reflux-precipitation polymerization (RPP), subsequently decorated by Au nanoparticles (Au NPs) through in situ reduction and finally modified with zwitterionic groups. 28049584 6 16 theme biological 1160:1169 arg1 samples 1171:1177 intricate biological samples 1150:1177 intricate biological samples 1150:1177 Furthermore, the prepared material was employed in the enrichment of glycopeptides in intricate biological samples, and 774 unique N-glycosylation sites from 411 N-glycosylated proteins were reliably identified in three replicate analyses of a 75μg protein sample extracted from mouse liver, suggesting wide application prospect in glycoproteomics. 28049584 2 17 gly glycopeptides 426:438 arg1 samples 453:459 complex samples 445:459 complex samples 445:459 In the work, we developed a magnetic zwitterionic-hydrophilic material for highly effective separation and analysis of glycopeptides from complex samples. 28049584 2 17 gly glycopeptides 426:438 arg2 glycopeptides 426:438 glycopeptides 426:438 glycopeptides from complex samples 426:459 In the work, we developed a magnetic zwitterionic-hydrophilic material for highly effective separation and analysis of glycopeptides from complex samples. 28049584 5 18 theme IgG 875:877 arg1 digest 879:884 5 fmol IgG digest 868:884 5 fmol IgG digest 868:884 Besides, the prepared Fe3O4@PGMA@Au-l-cys showed high detection sensitivity (5 fmol IgG digest), approving enrichment capacity (75mgg-1), satisfactory enrichment recovery (89.8%), and great performance in the analysis and profiling of low-abundance N-linked glycopeptides. 28049584 5 18 theme IgG 875:877 arg1 sensitivity 855:865 high detection sensitivity 840:865 high detection sensitivity (5 fmol IgG digest) 840:885 Besides, the prepared Fe3O4@PGMA@Au-l-cys showed high detection sensitivity (5 fmol IgG digest), approving enrichment capacity (75mgg-1), satisfactory enrichment recovery (89.8%), and great performance in the analysis and profiling of low-abundance N-linked glycopeptides. 28049584 6 19 theme N-glycosylation 1195:1209 arg1 sites 1211:1215 774 unique N-glycosylation sites 1184:1215 774 unique N-glycosylation sites from 411 N-glycosylated proteins 1184:1248 Furthermore, the prepared material was employed in the enrichment of glycopeptides in intricate biological samples, and 774 unique N-glycosylation sites from 411 N-glycosylated proteins were reliably identified in three replicate analyses of a 75μg protein sample extracted from mouse liver, suggesting wide application prospect in glycoproteomics. 28049584 3 20 theme Fe3O4 466:470 arg1 particles 472:480 The Fe3O4 particles 462:480 The Fe3O4 particles 462:480 The Fe3O4 particles were covered with a thick layer of polymer by one-step reflux-precipitation polymerization (RPP), subsequently decorated by Au nanoparticles (Au NPs) through in situ reduction and finally modified with zwitterionic groups. 28049584 6 21 theme intricate 1150:1158 arg1 samples 1171:1177 intricate biological samples 1150:1177 intricate biological samples 1150:1177 Furthermore, the prepared material was employed in the enrichment of glycopeptides in intricate biological samples, and 774 unique N-glycosylation sites from 411 N-glycosylated proteins were reliably identified in three replicate analyses of a 75μg protein sample extracted from mouse liver, suggesting wide application prospect in glycoproteomics. 28049584 6 22 gly N-glycosylation 1195:1209 arg2 sites 1211:1215 774 unique N-glycosylation sites 1184:1215 774 unique N-glycosylation sites from 411 N-glycosylated proteins 1184:1248 Furthermore, the prepared material was employed in the enrichment of glycopeptides in intricate biological samples, and 774 unique N-glycosylation sites from 411 N-glycosylated proteins were reliably identified in three replicate analyses of a 75μg protein sample extracted from mouse liver, suggesting wide application prospect in glycoproteomics. 28049584 6 22 gly N-glycosylation 1195:1209 arg2 774 1184:1186 774 1184:1186 774 1184:1186 Furthermore, the prepared material was employed in the enrichment of glycopeptides in intricate biological samples, and 774 unique N-glycosylation sites from 411 N-glycosylated proteins were reliably identified in three replicate analyses of a 75μg protein sample extracted from mouse liver, suggesting wide application prospect in glycoproteomics. 28049584 5 23 link N-linked 1040:1047 arg1 glycopeptides 1049:1061 low-abundance N-linked glycopeptides 1026:1061 low-abundance N-linked glycopeptides 1026:1061 Besides, the prepared Fe3O4@PGMA@Au-l-cys showed high detection sensitivity (5 fmol IgG digest), approving enrichment capacity (75mgg-1), satisfactory enrichment recovery (89.8%), and great performance in the analysis and profiling of low-abundance N-linked glycopeptides. 28049584 0 24 gly glycopeptides 97:109 arg2 glycopeptides 97:109 N-linked glycopeptides 88:109 N-linked glycopeptides 88:109 Synthesis of magnetic zwitterionic-hydrophilic material for the selective enrichment of N-linked glycopeptides. 28049584 2 25 theme glycopeptides 426:438 arg1 analysis 414:421 analysis 414:421 analysis of glycopeptides from complex samples 414:459 In the work, we developed a magnetic zwitterionic-hydrophilic material for highly effective separation and analysis of glycopeptides from complex samples. 28049584 2 25 theme glycopeptides 426:438 arg1 separation 399:408 highly effective separation 382:408 highly effective separation 382:408 In the work, we developed a magnetic zwitterionic-hydrophilic material for highly effective separation and analysis of glycopeptides from complex samples. 28049584 5 26 theme detection 845:853 arg1 digest 879:884 5 fmol IgG digest 868:884 5 fmol IgG digest 868:884 Besides, the prepared Fe3O4@PGMA@Au-l-cys showed high detection sensitivity (5 fmol IgG digest), approving enrichment capacity (75mgg-1), satisfactory enrichment recovery (89.8%), and great performance in the analysis and profiling of low-abundance N-linked glycopeptides. 28049584 5 26 theme detection 845:853 arg1 sensitivity 855:865 high detection sensitivity 840:865 high detection sensitivity (5 fmol IgG digest) 840:885 Besides, the prepared Fe3O4@PGMA@Au-l-cys showed high detection sensitivity (5 fmol IgG digest), approving enrichment capacity (75mgg-1), satisfactory enrichment recovery (89.8%), and great performance in the analysis and profiling of low-abundance N-linked glycopeptides. 28049584 5 27 theme PGMA 819:822 arg1 Au-l-cys 824:831 the prepared Fe3O4@PGMA@Au-l-cys 800:831 the prepared Fe3O4@PGMA@Au-l-cys 800:831 Besides, the prepared Fe3O4@PGMA@Au-l-cys showed high detection sensitivity (5 fmol IgG digest), approving enrichment capacity (75mgg-1), satisfactory enrichment recovery (89.8%), and great performance in the analysis and profiling of low-abundance N-linked glycopeptides. 28049584 6 28 gly glycopeptides 1133:1145 arg2 glycopeptides 1133:1145 glycopeptides 1133:1145 glycopeptides 1133:1145 Furthermore, the prepared material was employed in the enrichment of glycopeptides in intricate biological samples, and 774 unique N-glycosylation sites from 411 N-glycosylated proteins were reliably identified in three replicate analyses of a 75μg protein sample extracted from mouse liver, suggesting wide application prospect in glycoproteomics. 28049584 6 29 dep analyses 1294:1301 arg1 replicate 1284:1292 replicate 1284:1292 replicate 1284:1292 Furthermore, the prepared material was employed in the enrichment of glycopeptides in intricate biological samples, and 774 unique N-glycosylation sites from 411 N-glycosylated proteins were reliably identified in three replicate analyses of a 75μg protein sample extracted from mouse liver, suggesting wide application prospect in glycoproteomics. 28049584 1 30 theme efficient 199:207 arg1 method 209:214 the efficient method 195:214 the efficient method to separate and enrich glycopeptides from complex biological samples 195:283 In consideration of the close connection between glycopeptides and human diseases, the efficient method to separate and enrich glycopeptides from complex biological samples is urgently required. 28049584 6 31 theme wide 1367:1370 arg1 prospect 1384:1391 wide application prospect 1367:1391 wide application prospect in glycoproteomics 1367:1410 Furthermore, the prepared material was employed in the enrichment of glycopeptides in intricate biological samples, and 774 unique N-glycosylation sites from 411 N-glycosylated proteins were reliably identified in three replicate analyses of a 75μg protein sample extracted from mouse liver, suggesting wide application prospect in glycoproteomics. 28049584 6 32 theme prepared 1081:1088 arg1 material 1090:1097 the prepared material 1077:1097 the prepared material 1077:1097 Furthermore, the prepared material was employed in the enrichment of glycopeptides in intricate biological samples, and 774 unique N-glycosylation sites from 411 N-glycosylated proteins were reliably identified in three replicate analyses of a 75μg protein sample extracted from mouse liver, suggesting wide application prospect in glycoproteomics. 28049584 0 33 theme zwitterionic-hydrophilic 22:45 arg1 material 47:54 magnetic zwitterionic-hydrophilic material 13:54 magnetic zwitterionic-hydrophilic material 13:54 Synthesis of magnetic zwitterionic-hydrophilic material for the selective enrichment of N-linked glycopeptides. 28049584 6 34 theme N-glycosylated 1226:1239 arg1 proteins 1241:1248 411 N-glycosylated proteins 1222:1248 411 N-glycosylated proteins 1222:1248 Furthermore, the prepared material was employed in the enrichment of glycopeptides in intricate biological samples, and 774 unique N-glycosylation sites from 411 N-glycosylated proteins were reliably identified in three replicate analyses of a 75μg protein sample extracted from mouse liver, suggesting wide application prospect in glycoproteomics. 28049584 2 35 from separation 399:408 arg1 samples 453:459 complex samples 445:459 complex samples 445:459 In the work, we developed a magnetic zwitterionic-hydrophilic material for highly effective separation and analysis of glycopeptides from complex samples. 28049584 3 36 theme thick 502:506 arg1 layer 508:512 a thick layer 500:512 a thick layer of polymer 500:523 The Fe3O4 particles were covered with a thick layer of polymer by one-step reflux-precipitation polymerization (RPP), subsequently decorated by Au nanoparticles (Au NPs) through in situ reduction and finally modified with zwitterionic groups. 28049584 0 37 theme magnetic 13:20 arg1 material 47:54 magnetic zwitterionic-hydrophilic material 13:54 magnetic zwitterionic-hydrophilic material 13:54 Synthesis of magnetic zwitterionic-hydrophilic material for the selective enrichment of N-linked glycopeptides. 28049584 6 38 from prospect 1384:1391 arg1 glycoproteomics 1396:1410 glycoproteomics 1396:1410 glycoproteomics 1396:1410 Furthermore, the prepared material was employed in the enrichment of glycopeptides in intricate biological samples, and 774 unique N-glycosylation sites from 411 N-glycosylated proteins were reliably identified in three replicate analyses of a 75μg protein sample extracted from mouse liver, suggesting wide application prospect in glycoproteomics. 28049584 6 39 theme application 1372:1382 arg1 prospect 1384:1391 wide application prospect 1367:1391 wide application prospect in glycoproteomics 1367:1410 Furthermore, the prepared material was employed in the enrichment of glycopeptides in intricate biological samples, and 774 unique N-glycosylation sites from 411 N-glycosylated proteins were reliably identified in three replicate analyses of a 75μg protein sample extracted from mouse liver, suggesting wide application prospect in glycoproteomics. 28049584 3 40 theme Au 606:607 arg1 nanoparticles 609:621 Au nanoparticles 606:621 Au nanoparticles (Au NPs) 606:630 The Fe3O4 particles were covered with a thick layer of polymer by one-step reflux-precipitation polymerization (RPP), subsequently decorated by Au nanoparticles (Au NPs) through in situ reduction and finally modified with zwitterionic groups. 28049584 3 40 theme Au 606:607 arg1 NPs 627:629 Au NPs 624:629 Au NPs 624:629 The Fe3O4 particles were covered with a thick layer of polymer by one-step reflux-precipitation polymerization (RPP), subsequently decorated by Au nanoparticles (Au NPs) through in situ reduction and finally modified with zwitterionic groups. 28049584 5 41 theme N-linked 1040:1047 arg1 glycopeptides 1049:1061 low-abundance N-linked glycopeptides 1026:1061 low-abundance N-linked glycopeptides 1026:1061 Besides, the prepared Fe3O4@PGMA@Au-l-cys showed high detection sensitivity (5 fmol IgG digest), approving enrichment capacity (75mgg-1), satisfactory enrichment recovery (89.8%), and great performance in the analysis and profiling of low-abundance N-linked glycopeptides. 28049584 1 42 theme separate 219:226 arg1 glycopeptides 239:251 separate and enrich glycopeptides 219:251 separate and enrich glycopeptides from complex biological samples 219:283 In consideration of the close connection between glycopeptides and human diseases, the efficient method to separate and enrich glycopeptides from complex biological samples is urgently required. 28049584 3 43 theme reflux-precipitation 537:556 arg1 polymerization 558:571 one-step reflux-precipitation polymerization 528:571 one-step reflux-precipitation polymerization (RPP) 528:577 The Fe3O4 particles were covered with a thick layer of polymer by one-step reflux-precipitation polymerization (RPP), subsequently decorated by Au nanoparticles (Au NPs) through in situ reduction and finally modified with zwitterionic groups. 28049584 3 43 theme reflux-precipitation 537:556 arg1 RPP 574:576 RPP 574:576 RPP 574:576 The Fe3O4 particles were covered with a thick layer of polymer by one-step reflux-precipitation polymerization (RPP), subsequently decorated by Au nanoparticles (Au NPs) through in situ reduction and finally modified with zwitterionic groups. 28049584 3 44 theme one-step 528:535 arg1 polymerization 558:571 one-step reflux-precipitation polymerization 528:571 one-step reflux-precipitation polymerization (RPP) 528:577 The Fe3O4 particles were covered with a thick layer of polymer by one-step reflux-precipitation polymerization (RPP), subsequently decorated by Au nanoparticles (Au NPs) through in situ reduction and finally modified with zwitterionic groups. 28049584 3 44 theme one-step 528:535 arg1 RPP 574:576 RPP 574:576 RPP 574:576 The Fe3O4 particles were covered with a thick layer of polymer by one-step reflux-precipitation polymerization (RPP), subsequently decorated by Au nanoparticles (Au NPs) through in situ reduction and finally modified with zwitterionic groups. 28049584 1 45 from samples 277:283 arg1 glycopeptides 239:251 separate and enrich glycopeptides 219:251 separate and enrich glycopeptides from complex biological samples 219:283 In consideration of the close connection between glycopeptides and human diseases, the efficient method to separate and enrich glycopeptides from complex biological samples is urgently required. 28049584 3 46 theme zwitterionic 684:695 arg1 groups 697:702 zwitterionic groups 684:702 zwitterionic groups 684:702 The Fe3O4 particles were covered with a thick layer of polymer by one-step reflux-precipitation polymerization (RPP), subsequently decorated by Au nanoparticles (Au NPs) through in situ reduction and finally modified with zwitterionic groups. 28049584 5 47 theme enrichment 898:907 arg1 75mgg-1 919:925 75mgg-1 919:925 75mgg-1 919:925 Besides, the prepared Fe3O4@PGMA@Au-l-cys showed high detection sensitivity (5 fmol IgG digest), approving enrichment capacity (75mgg-1), satisfactory enrichment recovery (89.8%), and great performance in the analysis and profiling of low-abundance N-linked glycopeptides. 28049584 5 47 theme enrichment 898:907 arg1 capacity 909:916 approving enrichment capacity 888:916 approving enrichment capacity (75mgg-1) 888:926 Besides, the prepared Fe3O4@PGMA@Au-l-cys showed high detection sensitivity (5 fmol IgG digest), approving enrichment capacity (75mgg-1), satisfactory enrichment recovery (89.8%), and great performance in the analysis and profiling of low-abundance N-linked glycopeptides. 28049584 0 48 theme material 47:54 arg1 Synthesis 0:8 Synthesis 0:8 Synthesis of magnetic zwitterionic-hydrophilic material for the selective enrichment of N-linked glycopeptides. 0:110 Synthesis of magnetic zwitterionic-hydrophilic material for the selective enrichment of N-linked glycopeptides. 28049584 4 49 gly glycopeptides 776:788 arg2 glycopeptides 776:788 glycopeptides 776:788 glycopeptides 776:788 The abundant zwitterionic sites facilitate the selective enrichment of glycopeptides. 28049584 4 50 theme selective 752:760 arg1 enrichment 762:771 the selective enrichment 748:771 the selective enrichment of glycopeptides 748:788 The abundant zwitterionic sites facilitate the selective enrichment of glycopeptides. 28049584 5 51 gly glycopeptides 1049:1061 arg2 glycopeptides 1049:1061 low-abundance N-linked glycopeptides 1026:1061 low-abundance N-linked glycopeptides 1026:1061 Besides, the prepared Fe3O4@PGMA@Au-l-cys showed high detection sensitivity (5 fmol IgG digest), approving enrichment capacity (75mgg-1), satisfactory enrichment recovery (89.8%), and great performance in the analysis and profiling of low-abundance N-linked glycopeptides. 28049584 1 52 theme enrich 232:237 arg1 glycopeptides 239:251 separate and enrich glycopeptides 219:251 separate and enrich glycopeptides from complex biological samples 219:283 In consideration of the close connection between glycopeptides and human diseases, the efficient method to separate and enrich glycopeptides from complex biological samples is urgently required. 28049584 0 53 theme selective 64:72 arg1 enrichment 74:83 the selective enrichment 60:83 the selective enrichment of N-linked glycopeptides 60:109 Synthesis of magnetic zwitterionic-hydrophilic material for the selective enrichment of N-linked glycopeptides. 28049584 4 54 theme abundant 709:716 arg1 sites 731:735 The abundant zwitterionic sites 705:735 The abundant zwitterionic sites 705:735 The abundant zwitterionic sites facilitate the selective enrichment of glycopeptides. 28049584 3 55 theme Au 624:625 arg1 nanoparticles 609:621 Au nanoparticles 606:621 Au nanoparticles (Au NPs) 606:630 The Fe3O4 particles were covered with a thick layer of polymer by one-step reflux-precipitation polymerization (RPP), subsequently decorated by Au nanoparticles (Au NPs) through in situ reduction and finally modified with zwitterionic groups. 28049584 3 55 theme Au 624:625 arg1 NPs 627:629 Au NPs 624:629 Au NPs 624:629 The Fe3O4 particles were covered with a thick layer of polymer by one-step reflux-precipitation polymerization (RPP), subsequently decorated by Au nanoparticles (Au NPs) through in situ reduction and finally modified with zwitterionic groups. 28049584 0 56 link N-linked 88:95 arg1 glycopeptides 97:109 N-linked glycopeptides 88:109 N-linked glycopeptides 88:109 Synthesis of magnetic zwitterionic-hydrophilic material for the selective enrichment of N-linked glycopeptides. 28049584 5 57 theme satisfactory 929:940 arg1 recovery 953:960 satisfactory enrichment recovery 929:960 satisfactory enrichment recovery (89.8%) 929:968 Besides, the prepared Fe3O4@PGMA@Au-l-cys showed high detection sensitivity (5 fmol IgG digest), approving enrichment capacity (75mgg-1), satisfactory enrichment recovery (89.8%), and great performance in the analysis and profiling of low-abundance N-linked glycopeptides. 28049584 5 57 theme satisfactory 929:940 arg1 % 967:967 89.8% 963:967 89.8% 963:967 Besides, the prepared Fe3O4@PGMA@Au-l-cys showed high detection sensitivity (5 fmol IgG digest), approving enrichment capacity (75mgg-1), satisfactory enrichment recovery (89.8%), and great performance in the analysis and profiling of low-abundance N-linked glycopeptides. 28049584 5 58 theme high 840:843 arg1 digest 879:884 5 fmol IgG digest 868:884 5 fmol IgG digest 868:884 Besides, the prepared Fe3O4@PGMA@Au-l-cys showed high detection sensitivity (5 fmol IgG digest), approving enrichment capacity (75mgg-1), satisfactory enrichment recovery (89.8%), and great performance in the analysis and profiling of low-abundance N-linked glycopeptides. 28049584 5 58 theme high 840:843 arg1 sensitivity 855:865 high detection sensitivity 840:865 high detection sensitivity (5 fmol IgG digest) 840:885 Besides, the prepared Fe3O4@PGMA@Au-l-cys showed high detection sensitivity (5 fmol IgG digest), approving enrichment capacity (75mgg-1), satisfactory enrichment recovery (89.8%), and great performance in the analysis and profiling of low-abundance N-linked glycopeptides. 28049584 1 59 gly glycopeptides 161:173 arg2 glycopeptides 161:173 glycopeptides 161:173 glycopeptides 161:173 In consideration of the close connection between glycopeptides and human diseases, the efficient method to separate and enrich glycopeptides from complex biological samples is urgently required. 28049584 5 60 theme glycopeptides 1049:1061 arg1 profiling 1013:1021 profiling 1013:1021 profiling 1013:1021 Besides, the prepared Fe3O4@PGMA@Au-l-cys showed high detection sensitivity (5 fmol IgG digest), approving enrichment capacity (75mgg-1), satisfactory enrichment recovery (89.8%), and great performance in the analysis and profiling of low-abundance N-linked glycopeptides. 28049584 5 60 theme glycopeptides 1049:1061 arg1 analysis 1000:1007 analysis 1000:1007 analysis 1000:1007 Besides, the prepared Fe3O4@PGMA@Au-l-cys showed high detection sensitivity (5 fmol IgG digest), approving enrichment capacity (75mgg-1), satisfactory enrichment recovery (89.8%), and great performance in the analysis and profiling of low-abundance N-linked glycopeptides. 28049584 1 61 theme close 136:140 arg1 connection 142:151 the close connection 132:151 the close connection between glycopeptides and human diseases 132:192 In consideration of the close connection between glycopeptides and human diseases, the efficient method to separate and enrich glycopeptides from complex biological samples is urgently required. 28049584 6 62 theme mouse 1343:1347 arg1 liver 1349:1353 mouse liver 1343:1353 mouse liver 1343:1353 Furthermore, the prepared material was employed in the enrichment of glycopeptides in intricate biological samples, and 774 unique N-glycosylation sites from 411 N-glycosylated proteins were reliably identified in three replicate analyses of a 75μg protein sample extracted from mouse liver, suggesting wide application prospect in glycoproteomics. 28049584 5 63 theme enrichment 942:951 arg1 recovery 953:960 satisfactory enrichment recovery 929:960 satisfactory enrichment recovery (89.8%) 929:968 Besides, the prepared Fe3O4@PGMA@Au-l-cys showed high detection sensitivity (5 fmol IgG digest), approving enrichment capacity (75mgg-1), satisfactory enrichment recovery (89.8%), and great performance in the analysis and profiling of low-abundance N-linked glycopeptides. 28049584 5 63 theme enrichment 942:951 arg1 % 967:967 89.8% 963:967 89.8% 963:967 Besides, the prepared Fe3O4@PGMA@Au-l-cys showed high detection sensitivity (5 fmol IgG digest), approving enrichment capacity (75mgg-1), satisfactory enrichment recovery (89.8%), and great performance in the analysis and profiling of low-abundance N-linked glycopeptides. 28049584 5 64 theme low-abundance 1026:1038 arg1 glycopeptides 1049:1061 low-abundance N-linked glycopeptides 1026:1061 low-abundance N-linked glycopeptides 1026:1061 Besides, the prepared Fe3O4@PGMA@Au-l-cys showed high detection sensitivity (5 fmol IgG digest), approving enrichment capacity (75mgg-1), satisfactory enrichment recovery (89.8%), and great performance in the analysis and profiling of low-abundance N-linked glycopeptides. 28049584 1 65 theme connection 142:151 arg1 consideration 115:127 consideration 115:127 consideration of the close connection between glycopeptides and human diseases 115:192 In consideration of the close connection between glycopeptides and human diseases, the efficient method to separate and enrich glycopeptides from complex biological samples is urgently required. 28049584 6 66 gly N-glycosylated 1226:1239 arg1 proteins 1241:1248 411 N-glycosylated proteins 1222:1248 411 N-glycosylated proteins 1222:1248 Furthermore, the prepared material was employed in the enrichment of glycopeptides in intricate biological samples, and 774 unique N-glycosylation sites from 411 N-glycosylated proteins were reliably identified in three replicate analyses of a 75μg protein sample extracted from mouse liver, suggesting wide application prospect in glycoproteomics. 28049584 5 67 dep analysis 1000:1007 arg1 the 996:998 the 996:998 the 996:998 Besides, the prepared Fe3O4@PGMA@Au-l-cys showed high detection sensitivity (5 fmol IgG digest), approving enrichment capacity (75mgg-1), satisfactory enrichment recovery (89.8%), and great performance in the analysis and profiling of low-abundance N-linked glycopeptides. 28049584 6 68 theme unique 1188:1193 arg1 sites 1211:1215 774 unique N-glycosylation sites 1184:1215 774 unique N-glycosylation sites from 411 N-glycosylated proteins 1184:1248 Furthermore, the prepared material was employed in the enrichment of glycopeptides in intricate biological samples, and 774 unique N-glycosylation sites from 411 N-glycosylated proteins were reliably identified in three replicate analyses of a 75μg protein sample extracted from mouse liver, suggesting wide application prospect in glycoproteomics. 28049584 4 69 theme glycopeptides 776:788 arg1 enrichment 762:771 the selective enrichment 748:771 the selective enrichment of glycopeptides 748:788 The abundant zwitterionic sites facilitate the selective enrichment of glycopeptides. 28049584 2 70 from samples 453:459 arg1 glycopeptides 426:438 glycopeptides 426:438 glycopeptides from complex samples 426:459 In the work, we developed a magnetic zwitterionic-hydrophilic material for highly effective separation and analysis of glycopeptides from complex samples. 28049584 2 70 from samples 453:459 arg1 analysis 414:421 analysis 414:421 analysis of glycopeptides from complex samples 414:459 In the work, we developed a magnetic zwitterionic-hydrophilic material for highly effective separation and analysis of glycopeptides from complex samples. 28049584 2 70 from samples 453:459 arg1 separation 399:408 highly effective separation 382:408 highly effective separation 382:408 In the work, we developed a magnetic zwitterionic-hydrophilic material for highly effective separation and analysis of glycopeptides from complex samples. 28049584 2 71 theme magnetic 335:342 arg1 material 369:376 a magnetic zwitterionic-hydrophilic material 333:376 a magnetic zwitterionic-hydrophilic material for highly effective separation and analysis of glycopeptides from complex samples 333:459 In the work, we developed a magnetic zwitterionic-hydrophilic material for highly effective separation and analysis of glycopeptides from complex samples. 28049584 2 72 theme zwitterionic-hydrophilic 344:367 arg1 material 369:376 a magnetic zwitterionic-hydrophilic material 333:376 a magnetic zwitterionic-hydrophilic material for highly effective separation and analysis of glycopeptides from complex samples 333:459 In the work, we developed a magnetic zwitterionic-hydrophilic material for highly effective separation and analysis of glycopeptides from complex samples. 28049584 5 73 theme prepared 804:811 arg1 Au-l-cys 824:831 the prepared Fe3O4@PGMA@Au-l-cys 800:831 the prepared Fe3O4@PGMA@Au-l-cys 800:831 Besides, the prepared Fe3O4@PGMA@Au-l-cys showed high detection sensitivity (5 fmol IgG digest), approving enrichment capacity (75mgg-1), satisfactory enrichment recovery (89.8%), and great performance in the analysis and profiling of low-abundance N-linked glycopeptides. 28049584 2 74 theme complex 445:451 arg1 samples 453:459 complex samples 445:459 complex samples 445:459 In the work, we developed a magnetic zwitterionic-hydrophilic material for highly effective separation and analysis of glycopeptides from complex samples. 28049584 3 75 theme in 640:641 arg1 reduction 648:656 in situ reduction 640:656 in situ reduction 640:656 The Fe3O4 particles were covered with a thick layer of polymer by one-step reflux-precipitation polymerization (RPP), subsequently decorated by Au nanoparticles (Au NPs) through in situ reduction and finally modified with zwitterionic groups. 28049584 3 76 dep in 640:641 arg1 situ 643:646 situ 643:646 situ 643:646 The Fe3O4 particles were covered with a thick layer of polymer by one-step reflux-precipitation polymerization (RPP), subsequently decorated by Au nanoparticles (Au NPs) through in situ reduction and finally modified with zwitterionic groups. 28049584 5 77 theme approving 888:896 arg1 75mgg-1 919:925 75mgg-1 919:925 75mgg-1 919:925 Besides, the prepared Fe3O4@PGMA@Au-l-cys showed high detection sensitivity (5 fmol IgG digest), approving enrichment capacity (75mgg-1), satisfactory enrichment recovery (89.8%), and great performance in the analysis and profiling of low-abundance N-linked glycopeptides. 28049584 5 77 theme approving 888:896 arg1 capacity 909:916 approving enrichment capacity 888:916 approving enrichment capacity (75mgg-1) 888:926 Besides, the prepared Fe3O4@PGMA@Au-l-cys showed high detection sensitivity (5 fmol IgG digest), approving enrichment capacity (75mgg-1), satisfactory enrichment recovery (89.8%), and great performance in the analysis and profiling of low-abundance N-linked glycopeptides. 28049584 1 78 theme complex 258:264 arg1 samples 277:283 complex biological samples 258:283 complex biological samples 258:283 In consideration of the close connection between glycopeptides and human diseases, the efficient method to separate and enrich glycopeptides from complex biological samples is urgently required. 28049584 5 79 theme Fe3O4 813:817 arg1 Au-l-cys 824:831 the prepared Fe3O4@PGMA@Au-l-cys 800:831 the prepared Fe3O4@PGMA@Au-l-cys 800:831 Besides, the prepared Fe3O4@PGMA@Au-l-cys showed high detection sensitivity (5 fmol IgG digest), approving enrichment capacity (75mgg-1), satisfactory enrichment recovery (89.8%), and great performance in the analysis and profiling of low-abundance N-linked glycopeptides. 28049584 5 80 theme great 975:979 arg1 performance 981:991 great performance 975:991 great performance 975:991 Besides, the prepared Fe3O4@PGMA@Au-l-cys showed high detection sensitivity (5 fmol IgG digest), approving enrichment capacity (75mgg-1), satisfactory enrichment recovery (89.8%), and great performance in the analysis and profiling of low-abundance N-linked glycopeptides. 28049584 6 81 theme glycopeptides 1133:1145 arg1 enrichment 1119:1128 the enrichment 1115:1128 the enrichment of glycopeptides in intricate biological samples 1115:1177 Furthermore, the prepared material was employed in the enrichment of glycopeptides in intricate biological samples, and 774 unique N-glycosylation sites from 411 N-glycosylated proteins were reliably identified in three replicate analyses of a 75μg protein sample extracted from mouse liver, suggesting wide application prospect in glycoproteomics. 28049584 4 82 theme zwitterionic 718:729 arg1 sites 731:735 The abundant zwitterionic sites 705:735 The abundant zwitterionic sites 705:735 The abundant zwitterionic sites facilitate the selective enrichment of glycopeptides. 28049584 1 83 theme biological 266:275 arg1 samples 277:283 complex biological samples 258:283 complex biological samples 258:283 In consideration of the close connection between glycopeptides and human diseases, the efficient method to separate and enrich glycopeptides from complex biological samples is urgently required. 26352466 5 0 from roles 1192:1196 arg1 interactions 1257:1268 host pathogen interactions 1243:1268 host pathogen interactions 1243:1268 The uniquely modified glycoconjugates represent valuable tools for investigating the roles of C. jejuni cell surface glycoconjugates in host pathogen interactions. 26352466 4 1 theme site-specific 978:990 arg1 introduction 992:1003 site-specific introduction 978:1003 site-specific introduction of azide functionality for orthogonal labeling at three specific sites in the heptasaccharide glycan 978:1104 In vitro analyses reveal that chemoenzymatic approaches are useful for the preparation of undecaprenol diphosphate-linked glycans and glycopeptides with site-specific introduction of azide functionality for orthogonal labeling at three specific sites in the heptasaccharide glycan. 26352466 1 2 theme pivotal 173:179 arg1 roles 181:185 pivotal roles 173:185 pivotal roles 173:185 The cell surfaces of bacteria are replete with diverse glycoconjugates that play pivotal roles in determining how bacteria interact with the environment and the hosts that they colonize. 26352466 5 3 theme host 1243:1246 arg1 interactions 1257:1268 host pathogen interactions 1243:1268 host pathogen interactions 1243:1268 The uniquely modified glycoconjugates represent valuable tools for investigating the roles of C. jejuni cell surface glycoconjugates in host pathogen interactions. 26352466 3 4 link N-linked 600:607 arg1 Pgl 632:634 Pgl 632:634 Pgl 632:634 Herein, enzymes in the N-linked protein glycosylation (Pgl) pathway of Campylobacter jejuni are evaluated for their tolerance for azide-modified UDP-sugar substrates, including derivatives of 2,4-diacetamidobacillosamine and N-acetylgalactosamine. 26352466 3 4 link N-linked 600:607 arg1 glycosylation 617:629 N-linked protein glycosylation 600:629 the N-linked protein glycosylation (Pgl) pathway of Campylobacter jejuni 596:667 Herein, enzymes in the N-linked protein glycosylation (Pgl) pathway of Campylobacter jejuni are evaluated for their tolerance for azide-modified UDP-sugar substrates, including derivatives of 2,4-diacetamidobacillosamine and N-acetylgalactosamine. 26352466 3 5 theme UDP-sugar 722:730 arg1 substrates 732:741 azide-modified UDP-sugar substrates 707:741 azide-modified UDP-sugar substrates 707:741 Herein, enzymes in the N-linked protein glycosylation (Pgl) pathway of Campylobacter jejuni are evaluated for their tolerance for azide-modified UDP-sugar substrates, including derivatives of 2,4-diacetamidobacillosamine and N-acetylgalactosamine. 26352466 3 5 theme UDP-sugar 722:730 arg1 derivatives 754:764 derivatives 754:764 derivatives of 2,4-diacetamidobacillosamine and N-acetylgalactosamine 754:822 Herein, enzymes in the N-linked protein glycosylation (Pgl) pathway of Campylobacter jejuni are evaluated for their tolerance for azide-modified UDP-sugar substrates, including derivatives of 2,4-diacetamidobacillosamine and N-acetylgalactosamine. 26352466 4 6 theme glycopeptides 959:971 arg1 preparation 900:910 the preparation 896:910 the preparation of undecaprenol diphosphate-linked glycans and glycopeptides with site-specific introduction of azide functionality for orthogonal labeling at three specific sites in the heptasaccharide glycan 896:1104 In vitro analyses reveal that chemoenzymatic approaches are useful for the preparation of undecaprenol diphosphate-linked glycans and glycopeptides with site-specific introduction of azide functionality for orthogonal labeling at three specific sites in the heptasaccharide glycan. 26352466 2 7 theme imaging 561:567 arg1 agents 569:574 imaging agents 561:574 imaging agents 561:574 Studies to advance our understanding of these interactions rely on the availability of chemically defined glycoconjugates that can be selectively modified under orthogonal reaction conditions to serve as discrete ligands to probe biological interactions, in displayed arrays and as imaging agents. 26352466 4 8 theme undecaprenol 915:926 arg1 glycans 947:953 undecaprenol diphosphate-linked glycans 915:953 undecaprenol diphosphate-linked glycans 915:953 In vitro analyses reveal that chemoenzymatic approaches are useful for the preparation of undecaprenol diphosphate-linked glycans and glycopeptides with site-specific introduction of azide functionality for orthogonal labeling at three specific sites in the heptasaccharide glycan. 26352466 3 9 theme 2,4-diacetamidobacillosamine 769:796 arg1 derivatives 754:764 derivatives 754:764 derivatives of 2,4-diacetamidobacillosamine and N-acetylgalactosamine 754:822 Herein, enzymes in the N-linked protein glycosylation (Pgl) pathway of Campylobacter jejuni are evaluated for their tolerance for azide-modified UDP-sugar substrates, including derivatives of 2,4-diacetamidobacillosamine and N-acetylgalactosamine. 26352466 2 10 theme defined 377:383 arg1 glycoconjugates 385:399 chemically defined glycoconjugates 366:399 chemically defined glycoconjugates that can be selectively modified under orthogonal reaction conditions to serve as discrete ligands to probe biological interactions, in displayed arrays and as imaging agents 366:574 Studies to advance our understanding of these interactions rely on the availability of chemically defined glycoconjugates that can be selectively modified under orthogonal reaction conditions to serve as discrete ligands to probe biological interactions, in displayed arrays and as imaging agents. 26352466 2 10 theme defined 377:383 arg1 ligands 492:498 discrete ligands 483:498 discrete ligands 483:498 Studies to advance our understanding of these interactions rely on the availability of chemically defined glycoconjugates that can be selectively modified under orthogonal reaction conditions to serve as discrete ligands to probe biological interactions, in displayed arrays and as imaging agents. 26352466 4 11 from sites 1070:1074 arg1 glycan 1099:1104 the heptasaccharide glycan 1079:1104 the heptasaccharide glycan 1079:1104 In vitro analyses reveal that chemoenzymatic approaches are useful for the preparation of undecaprenol diphosphate-linked glycans and glycopeptides with site-specific introduction of azide functionality for orthogonal labeling at three specific sites in the heptasaccharide glycan. 26352466 4 11 from sites 1070:1074 arg1 labeling 1043:1050 orthogonal labeling 1032:1050 orthogonal labeling at three specific sites in the heptasaccharide glycan 1032:1104 In vitro analyses reveal that chemoenzymatic approaches are useful for the preparation of undecaprenol diphosphate-linked glycans and glycopeptides with site-specific introduction of azide functionality for orthogonal labeling at three specific sites in the heptasaccharide glycan. 26352466 4 12 theme heptasaccharide 1083:1097 arg1 glycan 1099:1104 the heptasaccharide glycan 1079:1104 the heptasaccharide glycan 1079:1104 In vitro analyses reveal that chemoenzymatic approaches are useful for the preparation of undecaprenol diphosphate-linked glycans and glycopeptides with site-specific introduction of azide functionality for orthogonal labeling at three specific sites in the heptasaccharide glycan. 26352466 5 13 theme pathogen 1248:1255 arg1 interactions 1257:1268 host pathogen interactions 1243:1268 host pathogen interactions 1243:1268 The uniquely modified glycoconjugates represent valuable tools for investigating the roles of C. jejuni cell surface glycoconjugates in host pathogen interactions. 26352466 4 14 theme glycans 947:953 arg1 preparation 900:910 the preparation 896:910 the preparation of undecaprenol diphosphate-linked glycans and glycopeptides with site-specific introduction of azide functionality for orthogonal labeling at three specific sites in the heptasaccharide glycan 896:1104 In vitro analyses reveal that chemoenzymatic approaches are useful for the preparation of undecaprenol diphosphate-linked glycans and glycopeptides with site-specific introduction of azide functionality for orthogonal labeling at three specific sites in the heptasaccharide glycan. 26352466 4 15 theme chemoenzymatic 855:868 arg1 approaches 870:879 chemoenzymatic approaches 855:879 chemoenzymatic approaches 855:879 In vitro analyses reveal that chemoenzymatic approaches are useful for the preparation of undecaprenol diphosphate-linked glycans and glycopeptides with site-specific introduction of azide functionality for orthogonal labeling at three specific sites in the heptasaccharide glycan. 26352466 4 16 link diphosphate-linked 928:945 arg1 glycans 947:953 undecaprenol diphosphate-linked glycans 915:953 undecaprenol diphosphate-linked glycans 915:953 In vitro analyses reveal that chemoenzymatic approaches are useful for the preparation of undecaprenol diphosphate-linked glycans and glycopeptides with site-specific introduction of azide functionality for orthogonal labeling at three specific sites in the heptasaccharide glycan. 26352466 4 17 theme diphosphate-linked 928:945 arg1 glycans 947:953 undecaprenol diphosphate-linked glycans 915:953 undecaprenol diphosphate-linked glycans 915:953 In vitro analyses reveal that chemoenzymatic approaches are useful for the preparation of undecaprenol diphosphate-linked glycans and glycopeptides with site-specific introduction of azide functionality for orthogonal labeling at three specific sites in the heptasaccharide glycan. 26352466 1 18 theme cell 96:99 arg1 replete 126:132 replete 126:132 replete with diverse glycoconjugates that play pivotal roles in determining how bacteria interact with the environment and the hosts that they colonize 126:276 The cell surfaces of bacteria are replete with diverse glycoconjugates that play pivotal roles in determining how bacteria interact with the environment and the hosts that they colonize. 26352466 1 18 theme cell 96:99 arg1 surfaces 101:108 The cell surfaces 92:108 The cell surfaces of bacteria 92:120 The cell surfaces of bacteria are replete with diverse glycoconjugates that play pivotal roles in determining how bacteria interact with the environment and the hosts that they colonize. 26352466 2 19 theme discrete 483:490 arg1 glycoconjugates 385:399 chemically defined glycoconjugates 366:399 chemically defined glycoconjugates that can be selectively modified under orthogonal reaction conditions to serve as discrete ligands to probe biological interactions, in displayed arrays and as imaging agents 366:574 Studies to advance our understanding of these interactions rely on the availability of chemically defined glycoconjugates that can be selectively modified under orthogonal reaction conditions to serve as discrete ligands to probe biological interactions, in displayed arrays and as imaging agents. 26352466 2 19 theme discrete 483:490 arg1 ligands 492:498 discrete ligands 483:498 discrete ligands 483:498 Studies to advance our understanding of these interactions rely on the availability of chemically defined glycoconjugates that can be selectively modified under orthogonal reaction conditions to serve as discrete ligands to probe biological interactions, in displayed arrays and as imaging agents. 26352466 1 20 with replete 126:132 arg1 glycoconjugates 147:161 diverse glycoconjugates 139:161 diverse glycoconjugates that play pivotal roles in determining how bacteria interact with the environment and the hosts that they colonize 139:276 The cell surfaces of bacteria are replete with diverse glycoconjugates that play pivotal roles in determining how bacteria interact with the environment and the hosts that they colonize. 26352466 2 21 dep Studies 279:285 arg1 advance 290:296 advance 290:296 to advance our understanding of these interactions 287:336 Studies to advance our understanding of these interactions rely on the availability of chemically defined glycoconjugates that can be selectively modified under orthogonal reaction conditions to serve as discrete ligands to probe biological interactions, in displayed arrays and as imaging agents. 26352466 0 22 theme Chemoenzymatic 0:13 arg1 Assembly 15:22 Chemoenzymatic Assembly 0:22 Chemoenzymatic Assembly of Bacterial Glycoconjugates for Site-Specific Orthogonal Labeling 0:89 Chemoenzymatic Assembly of Bacterial Glycoconjugates for Site-Specific Orthogonal Labeling. 26352466 2 23 theme interactions 325:336 arg1 understanding 302:314 our understanding 298:314 our understanding of these interactions 298:336 Studies to advance our understanding of these interactions rely on the availability of chemically defined glycoconjugates that can be selectively modified under orthogonal reaction conditions to serve as discrete ligands to probe biological interactions, in displayed arrays and as imaging agents. 26352466 0 24 theme Bacterial 27:35 arg1 Glycoconjugates 37:51 Bacterial Glycoconjugates 27:51 Bacterial Glycoconjugates 27:51 Chemoenzymatic Assembly of Bacterial Glycoconjugates for Site-Specific Orthogonal Labeling. 26352466 1 25 theme bacteria 113:120 arg1 replete 126:132 replete 126:132 replete with diverse glycoconjugates that play pivotal roles in determining how bacteria interact with the environment and the hosts that they colonize 126:276 The cell surfaces of bacteria are replete with diverse glycoconjugates that play pivotal roles in determining how bacteria interact with the environment and the hosts that they colonize. 26352466 1 25 theme bacteria 113:120 arg1 surfaces 101:108 The cell surfaces 92:108 The cell surfaces of bacteria 92:120 The cell surfaces of bacteria are replete with diverse glycoconjugates that play pivotal roles in determining how bacteria interact with the environment and the hosts that they colonize. 26352466 3 26 theme N-linked 600:607 arg1 Pgl 632:634 Pgl 632:634 Pgl 632:634 Herein, enzymes in the N-linked protein glycosylation (Pgl) pathway of Campylobacter jejuni are evaluated for their tolerance for azide-modified UDP-sugar substrates, including derivatives of 2,4-diacetamidobacillosamine and N-acetylgalactosamine. 26352466 3 26 theme N-linked 600:607 arg1 glycosylation 617:629 N-linked protein glycosylation 600:629 the N-linked protein glycosylation (Pgl) pathway of Campylobacter jejuni 596:667 Herein, enzymes in the N-linked protein glycosylation (Pgl) pathway of Campylobacter jejuni are evaluated for their tolerance for azide-modified UDP-sugar substrates, including derivatives of 2,4-diacetamidobacillosamine and N-acetylgalactosamine. 26352466 3 27 theme N-acetylgalactosamine 802:822 arg1 derivatives 754:764 derivatives 754:764 derivatives of 2,4-diacetamidobacillosamine and N-acetylgalactosamine 754:822 Herein, enzymes in the N-linked protein glycosylation (Pgl) pathway of Campylobacter jejuni are evaluated for their tolerance for azide-modified UDP-sugar substrates, including derivatives of 2,4-diacetamidobacillosamine and N-acetylgalactosamine. 26352466 5 28 theme cell 1211:1214 arg1 glycoconjugates 1224:1238 C. jejuni cell surface glycoconjugates 1201:1238 C. jejuni cell surface glycoconjugates 1201:1238 The uniquely modified glycoconjugates represent valuable tools for investigating the roles of C. jejuni cell surface glycoconjugates in host pathogen interactions. 26352466 4 29 theme In 825:826 arg1 analyses 834:841 In vitro analyses 825:841 In vitro analyses 825:841 In vitro analyses reveal that chemoenzymatic approaches are useful for the preparation of undecaprenol diphosphate-linked glycans and glycopeptides with site-specific introduction of azide functionality for orthogonal labeling at three specific sites in the heptasaccharide glycan. 26352466 2 30 theme reaction 451:458 arg1 conditions 460:469 orthogonal reaction conditions 440:469 orthogonal reaction conditions 440:469 Studies to advance our understanding of these interactions rely on the availability of chemically defined glycoconjugates that can be selectively modified under orthogonal reaction conditions to serve as discrete ligands to probe biological interactions, in displayed arrays and as imaging agents. 26352466 2 31 theme biological 509:518 arg1 interactions 520:531 biological interactions 509:531 biological interactions 509:531 Studies to advance our understanding of these interactions rely on the availability of chemically defined glycoconjugates that can be selectively modified under orthogonal reaction conditions to serve as discrete ligands to probe biological interactions, in displayed arrays and as imaging agents. 26352466 4 32 theme specific 1061:1068 arg1 sites 1070:1074 three specific sites 1055:1074 three specific sites in the heptasaccharide glycan 1055:1104 In vitro analyses reveal that chemoenzymatic approaches are useful for the preparation of undecaprenol diphosphate-linked glycans and glycopeptides with site-specific introduction of azide functionality for orthogonal labeling at three specific sites in the heptasaccharide glycan. 26352466 5 33 theme surface 1216:1222 arg1 glycoconjugates 1224:1238 C. jejuni cell surface glycoconjugates 1201:1238 C. jejuni cell surface glycoconjugates 1201:1238 The uniquely modified glycoconjugates represent valuable tools for investigating the roles of C. jejuni cell surface glycoconjugates in host pathogen interactions. 26352466 2 34 theme orthogonal 440:449 arg1 conditions 460:469 orthogonal reaction conditions 440:469 orthogonal reaction conditions 440:469 Studies to advance our understanding of these interactions rely on the availability of chemically defined glycoconjugates that can be selectively modified under orthogonal reaction conditions to serve as discrete ligands to probe biological interactions, in displayed arrays and as imaging agents. 26352466 0 35 theme Glycoconjugates 37:51 arg1 Assembly 15:22 Chemoenzymatic Assembly 0:22 Chemoenzymatic Assembly of Bacterial Glycoconjugates for Site-Specific Orthogonal Labeling 0:89 Chemoenzymatic Assembly of Bacterial Glycoconjugates for Site-Specific Orthogonal Labeling. 26352466 3 36 theme jejuni 662:667 arg1 pathway 637:643 the N-linked protein glycosylation (Pgl) pathway 596:643 the N-linked protein glycosylation (Pgl) pathway of Campylobacter jejuni 596:667 Herein, enzymes in the N-linked protein glycosylation (Pgl) pathway of Campylobacter jejuni are evaluated for their tolerance for azide-modified UDP-sugar substrates, including derivatives of 2,4-diacetamidobacillosamine and N-acetylgalactosamine. 26352466 4 37 gly glycopeptides 959:971 arg2 glycopeptides 959:971 glycopeptides 959:971 glycopeptides 959:971 In vitro analyses reveal that chemoenzymatic approaches are useful for the preparation of undecaprenol diphosphate-linked glycans and glycopeptides with site-specific introduction of azide functionality for orthogonal labeling at three specific sites in the heptasaccharide glycan. 26352466 0 38 theme Orthogonal 71:80 arg1 Labeling 82:89 Site-Specific Orthogonal Labeling 57:89 Site-Specific Orthogonal Labeling 57:89 Chemoenzymatic Assembly of Bacterial Glycoconjugates for Site-Specific Orthogonal Labeling. 26352466 4 39 theme functionality 1014:1026 arg1 introduction 992:1003 site-specific introduction 978:1003 site-specific introduction of azide functionality for orthogonal labeling at three specific sites in the heptasaccharide glycan 978:1104 In vitro analyses reveal that chemoenzymatic approaches are useful for the preparation of undecaprenol diphosphate-linked glycans and glycopeptides with site-specific introduction of azide functionality for orthogonal labeling at three specific sites in the heptasaccharide glycan. 26352466 3 40 theme protein 609:615 arg1 Pgl 632:634 Pgl 632:634 Pgl 632:634 Herein, enzymes in the N-linked protein glycosylation (Pgl) pathway of Campylobacter jejuni are evaluated for their tolerance for azide-modified UDP-sugar substrates, including derivatives of 2,4-diacetamidobacillosamine and N-acetylgalactosamine. 26352466 3 40 theme protein 609:615 arg1 glycosylation 617:629 N-linked protein glycosylation 600:629 the N-linked protein glycosylation (Pgl) pathway of Campylobacter jejuni 596:667 Herein, enzymes in the N-linked protein glycosylation (Pgl) pathway of Campylobacter jejuni are evaluated for their tolerance for azide-modified UDP-sugar substrates, including derivatives of 2,4-diacetamidobacillosamine and N-acetylgalactosamine. 26352466 0 41 theme Site-Specific 57:69 arg1 Labeling 82:89 Site-Specific Orthogonal Labeling 57:89 Site-Specific Orthogonal Labeling 57:89 Chemoenzymatic Assembly of Bacterial Glycoconjugates for Site-Specific Orthogonal Labeling. 26352466 4 42 theme azide 1008:1012 arg1 functionality 1014:1026 azide functionality 1008:1026 azide functionality 1008:1026 In vitro analyses reveal that chemoenzymatic approaches are useful for the preparation of undecaprenol diphosphate-linked glycans and glycopeptides with site-specific introduction of azide functionality for orthogonal labeling at three specific sites in the heptasaccharide glycan. 26352466 3 43 theme glycosylation 617:629 arg1 pathway 637:643 the N-linked protein glycosylation (Pgl) pathway 596:643 the N-linked protein glycosylation (Pgl) pathway of Campylobacter jejuni 596:667 Herein, enzymes in the N-linked protein glycosylation (Pgl) pathway of Campylobacter jejuni are evaluated for their tolerance for azide-modified UDP-sugar substrates, including derivatives of 2,4-diacetamidobacillosamine and N-acetylgalactosamine. 26352466 4 44 dep In 825:826 arg1 vitro 828:832 vitro 828:832 vitro 828:832 In vitro analyses reveal that chemoenzymatic approaches are useful for the preparation of undecaprenol diphosphate-linked glycans and glycopeptides with site-specific introduction of azide functionality for orthogonal labeling at three specific sites in the heptasaccharide glycan. 26352466 3 45 from enzymes 585:591 arg1 pathway 637:643 the N-linked protein glycosylation (Pgl) pathway 596:643 the N-linked protein glycosylation (Pgl) pathway of Campylobacter jejuni 596:667 Herein, enzymes in the N-linked protein glycosylation (Pgl) pathway of Campylobacter jejuni are evaluated for their tolerance for azide-modified UDP-sugar substrates, including derivatives of 2,4-diacetamidobacillosamine and N-acetylgalactosamine. 26352466 4 46 theme orthogonal 1032:1041 arg1 labeling 1043:1050 orthogonal labeling 1032:1050 orthogonal labeling at three specific sites in the heptasaccharide glycan 1032:1104 In vitro analyses reveal that chemoenzymatic approaches are useful for the preparation of undecaprenol diphosphate-linked glycans and glycopeptides with site-specific introduction of azide functionality for orthogonal labeling at three specific sites in the heptasaccharide glycan. 26352466 3 47 theme azide-modified 707:720 arg1 substrates 732:741 azide-modified UDP-sugar substrates 707:741 azide-modified UDP-sugar substrates 707:741 Herein, enzymes in the N-linked protein glycosylation (Pgl) pathway of Campylobacter jejuni are evaluated for their tolerance for azide-modified UDP-sugar substrates, including derivatives of 2,4-diacetamidobacillosamine and N-acetylgalactosamine. 26352466 3 47 theme azide-modified 707:720 arg1 derivatives 754:764 derivatives 754:764 derivatives of 2,4-diacetamidobacillosamine and N-acetylgalactosamine 754:822 Herein, enzymes in the N-linked protein glycosylation (Pgl) pathway of Campylobacter jejuni are evaluated for their tolerance for azide-modified UDP-sugar substrates, including derivatives of 2,4-diacetamidobacillosamine and N-acetylgalactosamine. 26352466 5 48 theme modified 1120:1127 arg1 glycoconjugates 1129:1143 The uniquely modified glycoconjugates 1107:1143 The uniquely modified glycoconjugates 1107:1143 The uniquely modified glycoconjugates represent valuable tools for investigating the roles of C. jejuni cell surface glycoconjugates in host pathogen interactions. 26352466 5 49 theme glycoconjugates 1224:1238 arg1 roles 1192:1196 the roles 1188:1196 the roles of C. jejuni cell surface glycoconjugates in host pathogen interactions 1188:1268 The uniquely modified glycoconjugates represent valuable tools for investigating the roles of C. jejuni cell surface glycoconjugates in host pathogen interactions. 26352466 1 50 theme diverse 139:145 arg1 glycoconjugates 147:161 diverse glycoconjugates 139:161 diverse glycoconjugates that play pivotal roles in determining how bacteria interact with the environment and the hosts that they colonize 139:276 The cell surfaces of bacteria are replete with diverse glycoconjugates that play pivotal roles in determining how bacteria interact with the environment and the hosts that they colonize. 26352466 1 51 dep they 264:267 arg1 hosts 253:257 the hosts 249:257 the hosts that they colonize 249:276 The cell surfaces of bacteria are replete with diverse glycoconjugates that play pivotal roles in determining how bacteria interact with the environment and the hosts that they colonize. 26352466 1 51 dep they 264:267 arg1 colonize 269:276 colonize 269:276 colonize 269:276 The cell surfaces of bacteria are replete with diverse glycoconjugates that play pivotal roles in determining how bacteria interact with the environment and the hosts that they colonize. 26352466 3 52 theme Campylobacter 648:660 arg1 jejuni 662:667 Campylobacter jejuni 648:667 Campylobacter jejuni 648:667 Herein, enzymes in the N-linked protein glycosylation (Pgl) pathway of Campylobacter jejuni are evaluated for their tolerance for azide-modified UDP-sugar substrates, including derivatives of 2,4-diacetamidobacillosamine and N-acetylgalactosamine. 26352466 5 53 theme C. 1201:1202 arg1 glycoconjugates 1224:1238 C. jejuni cell surface glycoconjugates 1201:1238 C. jejuni cell surface glycoconjugates 1201:1238 The uniquely modified glycoconjugates represent valuable tools for investigating the roles of C. jejuni cell surface glycoconjugates in host pathogen interactions. 26352466 2 54 theme displayed 537:545 arg1 arrays 547:552 displayed arrays 537:552 displayed arrays 537:552 Studies to advance our understanding of these interactions rely on the availability of chemically defined glycoconjugates that can be selectively modified under orthogonal reaction conditions to serve as discrete ligands to probe biological interactions, in displayed arrays and as imaging agents. 26352466 5 55 theme jejuni 1204:1209 arg1 glycoconjugates 1224:1238 C. jejuni cell surface glycoconjugates 1201:1238 C. jejuni cell surface glycoconjugates 1201:1238 The uniquely modified glycoconjugates represent valuable tools for investigating the roles of C. jejuni cell surface glycoconjugates in host pathogen interactions. 26352466 4 56 with preparation 900:910 arg1 introduction 992:1003 site-specific introduction 978:1003 site-specific introduction of azide functionality for orthogonal labeling at three specific sites in the heptasaccharide glycan 978:1104 In vitro analyses reveal that chemoenzymatic approaches are useful for the preparation of undecaprenol diphosphate-linked glycans and glycopeptides with site-specific introduction of azide functionality for orthogonal labeling at three specific sites in the heptasaccharide glycan. 26352466 5 57 theme valuable 1155:1162 arg1 tools 1164:1168 valuable tools 1155:1168 valuable tools for investigating the roles of C. jejuni cell surface glycoconjugates in host pathogen interactions 1155:1268 The uniquely modified glycoconjugates represent valuable tools for investigating the roles of C. jejuni cell surface glycoconjugates in host pathogen interactions. 26352466 2 58 theme glycoconjugates 385:399 arg1 availability 350:361 the availability 346:361 the availability of chemically defined glycoconjugates that can be selectively modified under orthogonal reaction conditions to serve as discrete ligands to probe biological interactions, in displayed arrays and as imaging agents 346:574 Studies to advance our understanding of these interactions rely on the availability of chemically defined glycoconjugates that can be selectively modified under orthogonal reaction conditions to serve as discrete ligands to probe biological interactions, in displayed arrays and as imaging agents. 25792706 4 0 theme STT3B 843:847 arg1 complex 849:855 the STT3B complex 839:855 the STT3B complex 839:855 Based upon pulse labeling experiments, 30-40% of STT3A-dependent glycosylation sites and 20% of STT3B-dependent sites are skipped in ALG6-congenital disorders of glycosylation fibroblasts supporting previous evidence that the STT3B complex has a relaxed preference for the fully assembled oligosaccharide donor. 25792706 6 1 theme MI8-5 1086:1090 arg1 cells 1092:1096 MI8-5 cells 1086:1096 MI8-5 cells 1086:1096 Protein immunoblot analysis and RT-PCR revealed that MI8-5 cells express 2-fold lower levels of STT3B than the parental Chinese hamster ovary cells. 25792706 8 2 from defect 1492:1497 arg1 pathway 1540:1546 the dolichol oligosaccharide assembly pathway 1502:1546 the dolichol oligosaccharide assembly pathway 1502:1546 Thus, differences in OST subunit expression can modify the severity of hypoglycosylation displayed by cells with a primary defect in the dolichol oligosaccharide assembly pathway. 25792706 3 3 theme asparagine-linked 480:496 arg1 glycosylation 498:510 asparagine-linked glycosylation 6 480:512 asparagine-linked glycosylation 6 (ALG6) deficient cell lines that assemble Dol-PP-GlcNAc(2)Man(9) as the largest oligosaccharide donor 480:614 We monitored glycosylation of proteins in asparagine-linked glycosylation 6 (ALG6) deficient cell lines that assemble Dol-PP-GlcNAc(2)Man(9) as the largest oligosaccharide donor. 25792706 3 3 theme asparagine-linked 480:496 arg1 ALG6 515:518 ALG6 515:518 ALG6 515:518 We monitored glycosylation of proteins in asparagine-linked glycosylation 6 (ALG6) deficient cell lines that assemble Dol-PP-GlcNAc(2)Man(9) as the largest oligosaccharide donor. 25792706 3 4 theme deficient 521:529 arg1 lines 536:540 asparagine-linked glycosylation 6 (ALG6) deficient cell lines 480:540 asparagine-linked glycosylation 6 (ALG6) deficient cell lines that assemble Dol-PP-GlcNAc(2)Man(9) as the largest oligosaccharide donor 480:614 We monitored glycosylation of proteins in asparagine-linked glycosylation 6 (ALG6) deficient cell lines that assemble Dol-PP-GlcNAc(2)Man(9) as the largest oligosaccharide donor. 25792706 4 5 theme previous 816:823 arg1 evidence 825:832 previous evidence that the STT3B complex has a relaxed preference for the fully assembled oligosaccharide donor 816:926 previous evidence that the STT3B complex has a relaxed preference for the fully assembled oligosaccharide donor 816:926 Based upon pulse labeling experiments, 30-40% of STT3A-dependent glycosylation sites and 20% of STT3B-dependent sites are skipped in ALG6-congenital disorders of glycosylation fibroblasts supporting previous evidence that the STT3B complex has a relaxed preference for the fully assembled oligosaccharide donor. 25792706 7 6 theme MI8-5 1356:1360 arg1 cells 1362:1366 MI8-5 cells 1356:1366 MI8-5 cells 1356:1366 The combination of reduced expression of STT3B and the lack of the optimal Dol-PP-GlcNAc(2)Man(9)Glc(3) donor synergize to cause very severe hypoglycosylation of proteins in MI8-5 cells. 25792706 1 7 theme donor 198:202 arg1 assembly 166:173 the assembly 162:173 the assembly of the oligosaccharide donor (Dol-PP-GlcNAc(2)Man(9)Glc(3)) for N-linked glycosylation 162:260 A defect in the assembly of the oligosaccharide donor (Dol-PP-GlcNAc(2)Man(9)Glc(3)) for N-linked glycosylation causes hypoglycosylation of proteins by the oligosaccharyltransferase (OST). 25792706 6 8 theme parental 1144:1151 arg1 cells 1175:1179 the parental Chinese hamster ovary cells 1140:1179 the parental Chinese hamster ovary cells 1140:1179 Protein immunoblot analysis and RT-PCR revealed that MI8-5 cells express 2-fold lower levels of STT3B than the parental Chinese hamster ovary cells. 25792706 1 9 theme Dol-PP-GlcNAc 205:217 arg1 Man 221:223 Dol-PP-GlcNAc(2)Man(9) 205:226 Dol-PP-GlcNAc(2)Man(9)Glc(3) 205:232 A defect in the assembly of the oligosaccharide donor (Dol-PP-GlcNAc(2)Man(9)Glc(3)) for N-linked glycosylation causes hypoglycosylation of proteins by the oligosaccharyltransferase (OST). 25792706 1 10 dep donor 198:202 arg1 Man 221:223 Dol-PP-GlcNAc(2)Man(9) 205:226 Dol-PP-GlcNAc(2)Man(9)Glc(3) 205:232 A defect in the assembly of the oligosaccharide donor (Dol-PP-GlcNAc(2)Man(9)Glc(3)) for N-linked glycosylation causes hypoglycosylation of proteins by the oligosaccharyltransferase (OST). 25792706 4 11 theme oligosaccharide 906:920 arg1 donor 922:926 the fully assembled oligosaccharide donor 886:926 the fully assembled oligosaccharide donor 886:926 Based upon pulse labeling experiments, 30-40% of STT3A-dependent glycosylation sites and 20% of STT3B-dependent sites are skipped in ALG6-congenital disorders of glycosylation fibroblasts supporting previous evidence that the STT3B complex has a relaxed preference for the fully assembled oligosaccharide donor. 25792706 4 12 theme relaxed 863:869 arg1 preference 871:880 a relaxed preference 861:880 a relaxed preference for the fully assembled oligosaccharide donor 861:926 Based upon pulse labeling experiments, 30-40% of STT3A-dependent glycosylation sites and 20% of STT3B-dependent sites are skipped in ALG6-congenital disorders of glycosylation fibroblasts supporting previous evidence that the STT3B complex has a relaxed preference for the fully assembled oligosaccharide donor. 25792706 7 13 from hypoglycosylation 1323:1339 arg1 cells 1362:1366 MI8-5 cells 1356:1366 MI8-5 cells 1356:1366 The combination of reduced expression of STT3B and the lack of the optimal Dol-PP-GlcNAc(2)Man(9)Glc(3) donor synergize to cause very severe hypoglycosylation of proteins in MI8-5 cells. 25792706 8 14 theme subunit 1394:1400 arg1 expression 1402:1411 OST subunit expression 1390:1411 OST subunit expression 1390:1411 Thus, differences in OST subunit expression can modify the severity of hypoglycosylation displayed by cells with a primary defect in the dolichol oligosaccharide assembly pathway. 25792706 7 15 theme donor 1286:1290 arg1 combination 1186:1196 The combination 1182:1196 The combination of reduced expression of STT3B 1182:1227 The combination of reduced expression of STT3B and the lack of the optimal Dol-PP-GlcNAc(2)Man(9)Glc(3) donor synergize to cause very severe hypoglycosylation of proteins in MI8-5 cells. 25792706 7 15 theme donor 1286:1290 arg1 lack 1237:1240 the lack 1233:1240 the lack of the optimal Dol-PP-GlcNAc(2)Man(9)Glc(3) donor 1233:1290 The combination of reduced expression of STT3B and the lack of the optimal Dol-PP-GlcNAc(2)Man(9)Glc(3) donor synergize to cause very severe hypoglycosylation of proteins in MI8-5 cells. 25792706 4 16 theme STT3A-dependent 666:680 arg1 sites 696:700 STT3A-dependent glycosylation sites 666:700 STT3A-dependent glycosylation sites 666:700 Based upon pulse labeling experiments, 30-40% of STT3A-dependent glycosylation sites and 20% of STT3B-dependent sites are skipped in ALG6-congenital disorders of glycosylation fibroblasts supporting previous evidence that the STT3B complex has a relaxed preference for the fully assembled oligosaccharide donor. 25792706 3 17 from lines 536:540 arg1 glycosylation 451:463 glycosylation 451:463 glycosylation of proteins in asparagine-linked glycosylation 6 (ALG6) deficient cell lines that assemble Dol-PP-GlcNAc(2)Man(9) as the largest oligosaccharide donor 451:614 We monitored glycosylation of proteins in asparagine-linked glycosylation 6 (ALG6) deficient cell lines that assemble Dol-PP-GlcNAc(2)Man(9) as the largest oligosaccharide donor. 25792706 7 18 theme Man 1273:1275 arg1 donor 1286:1290 the optimal Dol-PP-GlcNAc(2)Man(9)Glc(3) donor 1245:1290 the optimal Dol-PP-GlcNAc(2)Man(9)Glc(3) donor 1245:1290 The combination of reduced expression of STT3B and the lack of the optimal Dol-PP-GlcNAc(2)Man(9)Glc(3) donor synergize to cause very severe hypoglycosylation of proteins in MI8-5 cells. 25792706 4 19 theme labeling 634:641 arg1 experiments 643:653 pulse labeling experiments 628:653 pulse labeling experiments 628:653 Based upon pulse labeling experiments, 30-40% of STT3A-dependent glycosylation sites and 20% of STT3B-dependent sites are skipped in ALG6-congenital disorders of glycosylation fibroblasts supporting previous evidence that the STT3B complex has a relaxed preference for the fully assembled oligosaccharide donor. 25792706 7 20 theme STT3B 1223:1227 arg1 expression 1209:1218 reduced expression 1201:1218 reduced expression of STT3B 1201:1227 The combination of reduced expression of STT3B and the lack of the optimal Dol-PP-GlcNAc(2)Man(9)Glc(3) donor synergize to cause very severe hypoglycosylation of proteins in MI8-5 cells. 25792706 7 21 theme expression 1209:1218 arg1 combination 1186:1196 The combination 1182:1196 The combination of reduced expression of STT3B 1182:1227 The combination of reduced expression of STT3B and the lack of the optimal Dol-PP-GlcNAc(2)Man(9)Glc(3) donor synergize to cause very severe hypoglycosylation of proteins in MI8-5 cells. 25792706 7 21 theme expression 1209:1218 arg1 lack 1237:1240 the lack 1233:1240 the lack of the optimal Dol-PP-GlcNAc(2)Man(9)Glc(3) donor 1233:1290 The combination of reduced expression of STT3B and the lack of the optimal Dol-PP-GlcNAc(2)Man(9)Glc(3) donor synergize to cause very severe hypoglycosylation of proteins in MI8-5 cells. 25792706 5 22 theme sites 962:966 arg1 Glycosylation 929:941 Glycosylation 929:941 Glycosylation of STT3B-dependent sites 929:966 Glycosylation of STT3B-dependent sites was more severely reduced in the ALG6 deficient MI8-5 cell line. 25792706 8 23 with cells 1471:1475 arg1 defect 1492:1497 a primary defect 1482:1497 a primary defect in the dolichol oligosaccharide assembly pathway 1482:1546 Thus, differences in OST subunit expression can modify the severity of hypoglycosylation displayed by cells with a primary defect in the dolichol oligosaccharide assembly pathway. 25792706 4 24 theme sites 729:733 arg1 % 661:661 30-40% 656:661 30-40% of STT3A-dependent glycosylation sites 656:700 Based upon pulse labeling experiments, 30-40% of STT3A-dependent glycosylation sites and 20% of STT3B-dependent sites are skipped in ALG6-congenital disorders of glycosylation fibroblasts supporting previous evidence that the STT3B complex has a relaxed preference for the fully assembled oligosaccharide donor. 25792706 4 24 theme sites 729:733 arg1 sites 696:700 STT3A-dependent glycosylation sites 666:700 STT3A-dependent glycosylation sites 666:700 Based upon pulse labeling experiments, 30-40% of STT3A-dependent glycosylation sites and 20% of STT3B-dependent sites are skipped in ALG6-congenital disorders of glycosylation fibroblasts supporting previous evidence that the STT3B complex has a relaxed preference for the fully assembled oligosaccharide donor. 25792706 4 24 theme sites 729:733 arg1 % 708:708 20% 706:708 20% of STT3B-dependent sites 706:733 Based upon pulse labeling experiments, 30-40% of STT3A-dependent glycosylation sites and 20% of STT3B-dependent sites are skipped in ALG6-congenital disorders of glycosylation fibroblasts supporting previous evidence that the STT3B complex has a relaxed preference for the fully assembled oligosaccharide donor. 25792706 4 24 theme sites 729:733 arg1 sites 729:733 STT3B-dependent sites 713:733 STT3B-dependent sites 713:733 Based upon pulse labeling experiments, 30-40% of STT3A-dependent glycosylation sites and 20% of STT3B-dependent sites are skipped in ALG6-congenital disorders of glycosylation fibroblasts supporting previous evidence that the STT3B complex has a relaxed preference for the fully assembled oligosaccharide donor. 25792706 0 25 theme oligosaccharide 127:141 arg1 donor 143:147 the fully assembled oligosaccharide donor 107:147 the fully assembled oligosaccharide donor 107:147 Reduced expression of the oligosaccharyltransferase exacerbates protein hypoglycosylation in cells lacking the fully assembled oligosaccharide donor. 25792706 2 26 dep subunits 411:418 arg1 STT3A 421:425 STT3A 421:425 STT3A 421:425 Mammalian cells express two OST complexes that have different catalytic subunits (STT3A or STT3B). 25792706 2 26 dep subunits 411:418 arg1 subunits 411:418 different catalytic subunits 391:418 different catalytic subunits (STT3A or STT3B) 391:435 Mammalian cells express two OST complexes that have different catalytic subunits (STT3A or STT3B). 25792706 2 26 dep subunits 411:418 arg1 STT3B 430:434 STT3B 430:434 STT3B 430:434 Mammalian cells express two OST complexes that have different catalytic subunits (STT3A or STT3B). 25792706 1 27 from defect 152:157 arg1 assembly 166:173 the assembly 162:173 the assembly of the oligosaccharide donor (Dol-PP-GlcNAc(2)Man(9)Glc(3)) for N-linked glycosylation 162:260 A defect in the assembly of the oligosaccharide donor (Dol-PP-GlcNAc(2)Man(9)Glc(3)) for N-linked glycosylation causes hypoglycosylation of proteins by the oligosaccharyltransferase (OST). 25792706 4 28 theme sites 696:700 arg1 % 661:661 30-40% 656:661 30-40% of STT3A-dependent glycosylation sites 656:700 Based upon pulse labeling experiments, 30-40% of STT3A-dependent glycosylation sites and 20% of STT3B-dependent sites are skipped in ALG6-congenital disorders of glycosylation fibroblasts supporting previous evidence that the STT3B complex has a relaxed preference for the fully assembled oligosaccharide donor. 25792706 4 28 theme sites 696:700 arg1 sites 696:700 STT3A-dependent glycosylation sites 666:700 STT3A-dependent glycosylation sites 666:700 Based upon pulse labeling experiments, 30-40% of STT3A-dependent glycosylation sites and 20% of STT3B-dependent sites are skipped in ALG6-congenital disorders of glycosylation fibroblasts supporting previous evidence that the STT3B complex has a relaxed preference for the fully assembled oligosaccharide donor. 25792706 4 28 theme sites 696:700 arg1 % 708:708 20% 706:708 20% of STT3B-dependent sites 706:733 Based upon pulse labeling experiments, 30-40% of STT3A-dependent glycosylation sites and 20% of STT3B-dependent sites are skipped in ALG6-congenital disorders of glycosylation fibroblasts supporting previous evidence that the STT3B complex has a relaxed preference for the fully assembled oligosaccharide donor. 25792706 4 28 theme sites 696:700 arg1 sites 729:733 STT3B-dependent sites 713:733 STT3B-dependent sites 713:733 Based upon pulse labeling experiments, 30-40% of STT3A-dependent glycosylation sites and 20% of STT3B-dependent sites are skipped in ALG6-congenital disorders of glycosylation fibroblasts supporting previous evidence that the STT3B complex has a relaxed preference for the fully assembled oligosaccharide donor. 25792706 0 29 theme Reduced 0:6 arg1 expression 8:17 Reduced expression 0:17 Reduced expression of the oligosaccharyltransferase 0:50 Reduced expression of the oligosaccharyltransferase exacerbates protein hypoglycosylation in cells lacking the fully assembled oligosaccharide donor. 25792706 3 30 gly glycosylation 451:463 arg1 proteins 468:475 proteins 468:475 proteins in asparagine-linked glycosylation 6 (ALG6) deficient cell lines that assemble Dol-PP-GlcNAc(2)Man(9) as the largest oligosaccharide donor 468:614 We monitored glycosylation of proteins in asparagine-linked glycosylation 6 (ALG6) deficient cell lines that assemble Dol-PP-GlcNAc(2)Man(9) as the largest oligosaccharide donor. 25792706 2 31 theme catalytic 401:409 arg1 STT3A 421:425 STT3A 421:425 STT3A 421:425 Mammalian cells express two OST complexes that have different catalytic subunits (STT3A or STT3B). 25792706 2 31 theme catalytic 401:409 arg1 subunits 411:418 different catalytic subunits 391:418 different catalytic subunits (STT3A or STT3B) 391:435 Mammalian cells express two OST complexes that have different catalytic subunits (STT3A or STT3B). 25792706 2 31 theme catalytic 401:409 arg1 STT3B 430:434 STT3B 430:434 STT3B 430:434 Mammalian cells express two OST complexes that have different catalytic subunits (STT3A or STT3B). 25792706 6 32 theme hamster 1161:1167 arg1 cells 1175:1179 the parental Chinese hamster ovary cells 1140:1179 the parental Chinese hamster ovary cells 1140:1179 Protein immunoblot analysis and RT-PCR revealed that MI8-5 cells express 2-fold lower levels of STT3B than the parental Chinese hamster ovary cells. 25792706 6 33 theme Protein 1033:1039 arg1 analysis 1052:1059 Protein immunoblot analysis 1033:1059 Protein immunoblot analysis 1033:1059 Protein immunoblot analysis and RT-PCR revealed that MI8-5 cells express 2-fold lower levels of STT3B than the parental Chinese hamster ovary cells. 25792706 3 34 theme oligosaccharide 594:608 arg1 Man 572:574 Dol-PP-GlcNAc(2)Man(9) 556:577 Dol-PP-GlcNAc(2)Man(9) 556:577 We monitored glycosylation of proteins in asparagine-linked glycosylation 6 (ALG6) deficient cell lines that assemble Dol-PP-GlcNAc(2)Man(9) as the largest oligosaccharide donor. 25792706 3 34 theme oligosaccharide 594:608 arg1 donor 610:614 the largest oligosaccharide donor 582:614 the largest oligosaccharide donor 582:614 We monitored glycosylation of proteins in asparagine-linked glycosylation 6 (ALG6) deficient cell lines that assemble Dol-PP-GlcNAc(2)Man(9) as the largest oligosaccharide donor. 25792706 0 35 theme oligosaccharyltransferase 26:50 arg1 expression 8:17 Reduced expression 0:17 Reduced expression of the oligosaccharyltransferase 0:50 Reduced expression of the oligosaccharyltransferase exacerbates protein hypoglycosylation in cells lacking the fully assembled oligosaccharide donor. 25792706 5 36 theme deficient 1006:1014 arg1 line 1027:1030 the ALG6 deficient MI8-5 cell line 997:1030 the ALG6 deficient MI8-5 cell line 997:1030 Glycosylation of STT3B-dependent sites was more severely reduced in the ALG6 deficient MI8-5 cell line. 25792706 4 37 theme fibroblasts 793:803 arg1 disorders 766:774 ALG6-congenital disorders 750:774 ALG6-congenital disorders of glycosylation fibroblasts supporting previous evidence that the STT3B complex has a relaxed preference for the fully assembled oligosaccharide donor 750:926 Based upon pulse labeling experiments, 30-40% of STT3A-dependent glycosylation sites and 20% of STT3B-dependent sites are skipped in ALG6-congenital disorders of glycosylation fibroblasts supporting previous evidence that the STT3B complex has a relaxed preference for the fully assembled oligosaccharide donor. 25792706 0 38 theme protein 64:70 arg1 hypoglycosylation 72:88 protein hypoglycosylation 64:88 protein hypoglycosylation 64:88 Reduced expression of the oligosaccharyltransferase exacerbates protein hypoglycosylation in cells lacking the fully assembled oligosaccharide donor. 25792706 1 39 theme proteins 290:297 arg1 hypoglycosylation 269:285 hypoglycosylation 269:285 hypoglycosylation of proteins 269:297 A defect in the assembly of the oligosaccharide donor (Dol-PP-GlcNAc(2)Man(9)Glc(3)) for N-linked glycosylation causes hypoglycosylation of proteins by the oligosaccharyltransferase (OST). 25792706 5 40 theme cell 1022:1025 arg1 line 1027:1030 the ALG6 deficient MI8-5 cell line 997:1030 the ALG6 deficient MI8-5 cell line 997:1030 Glycosylation of STT3B-dependent sites was more severely reduced in the ALG6 deficient MI8-5 cell line. 25792706 8 41 theme oligosaccharide 1515:1529 arg1 pathway 1540:1546 the dolichol oligosaccharide assembly pathway 1502:1546 the dolichol oligosaccharide assembly pathway 1502:1546 Thus, differences in OST subunit expression can modify the severity of hypoglycosylation displayed by cells with a primary defect in the dolichol oligosaccharide assembly pathway. 25792706 7 42 theme optimal 1249:1255 arg1 Man 1273:1275 the optimal Dol-PP-GlcNAc(2)Man(9) 1245:1278 the optimal Dol-PP-GlcNAc(2)Man(9)Glc(3) donor 1245:1290 The combination of reduced expression of STT3B and the lack of the optimal Dol-PP-GlcNAc(2)Man(9)Glc(3) donor synergize to cause very severe hypoglycosylation of proteins in MI8-5 cells. 25792706 4 43 theme ALG6-congenital 750:764 arg1 disorders 766:774 ALG6-congenital disorders 750:774 ALG6-congenital disorders of glycosylation fibroblasts supporting previous evidence that the STT3B complex has a relaxed preference for the fully assembled oligosaccharide donor 750:926 Based upon pulse labeling experiments, 30-40% of STT3A-dependent glycosylation sites and 20% of STT3B-dependent sites are skipped in ALG6-congenital disorders of glycosylation fibroblasts supporting previous evidence that the STT3B complex has a relaxed preference for the fully assembled oligosaccharide donor. 25792706 3 44 theme glycosylation 498:510 arg1 lines 536:540 asparagine-linked glycosylation 6 (ALG6) deficient cell lines 480:540 asparagine-linked glycosylation 6 (ALG6) deficient cell lines that assemble Dol-PP-GlcNAc(2)Man(9) as the largest oligosaccharide donor 480:614 We monitored glycosylation of proteins in asparagine-linked glycosylation 6 (ALG6) deficient cell lines that assemble Dol-PP-GlcNAc(2)Man(9) as the largest oligosaccharide donor. 25792706 0 45 gly hypoglycosylation 72:88 arg1 cells 93:97 cells 93:97 cells lacking the fully assembled oligosaccharide donor 93:147 Reduced expression of the oligosaccharyltransferase exacerbates protein hypoglycosylation in cells lacking the fully assembled oligosaccharide donor. 25792706 8 46 from differences 1375:1385 arg1 expression 1402:1411 OST subunit expression 1390:1411 OST subunit expression 1390:1411 Thus, differences in OST subunit expression can modify the severity of hypoglycosylation displayed by cells with a primary defect in the dolichol oligosaccharide assembly pathway. 25792706 1 47 link N-linked 239:246 arg1 glycosylation 248:260 N-linked glycosylation 239:260 N-linked glycosylation 239:260 A defect in the assembly of the oligosaccharide donor (Dol-PP-GlcNAc(2)Man(9)Glc(3)) for N-linked glycosylation causes hypoglycosylation of proteins by the oligosaccharyltransferase (OST). 25792706 7 48 gly hypoglycosylation 1323:1339 arg1 proteins 1344:1351 proteins 1344:1351 proteins 1344:1351 The combination of reduced expression of STT3B and the lack of the optimal Dol-PP-GlcNAc(2)Man(9)Glc(3) donor synergize to cause very severe hypoglycosylation of proteins in MI8-5 cells. 25792706 7 48 gly hypoglycosylation 1323:1339 arg1 cells 1362:1366 MI8-5 cells 1356:1366 MI8-5 cells 1356:1366 The combination of reduced expression of STT3B and the lack of the optimal Dol-PP-GlcNAc(2)Man(9)Glc(3) donor synergize to cause very severe hypoglycosylation of proteins in MI8-5 cells. 25792706 7 49 theme proteins 1344:1351 arg1 hypoglycosylation 1323:1339 very severe hypoglycosylation 1311:1339 very severe hypoglycosylation of proteins in MI8-5 cells 1311:1366 The combination of reduced expression of STT3B and the lack of the optimal Dol-PP-GlcNAc(2)Man(9)Glc(3) donor synergize to cause very severe hypoglycosylation of proteins in MI8-5 cells. 25792706 6 50 theme ovary 1169:1173 arg1 cells 1175:1179 the parental Chinese hamster ovary cells 1140:1179 the parental Chinese hamster ovary cells 1140:1179 Protein immunoblot analysis and RT-PCR revealed that MI8-5 cells express 2-fold lower levels of STT3B than the parental Chinese hamster ovary cells. 25792706 1 51 theme oligosaccharide 182:196 arg1 donor 198:202 the oligosaccharide donor 178:202 the oligosaccharide donor (Dol-PP-GlcNAc(2)Man(9)Glc(3)) for N-linked glycosylation 178:260 A defect in the assembly of the oligosaccharide donor (Dol-PP-GlcNAc(2)Man(9)Glc(3)) for N-linked glycosylation causes hypoglycosylation of proteins by the oligosaccharyltransferase (OST). 25792706 6 52 theme Chinese 1153:1159 arg1 cells 1175:1179 the parental Chinese hamster ovary cells 1140:1179 the parental Chinese hamster ovary cells 1140:1179 Protein immunoblot analysis and RT-PCR revealed that MI8-5 cells express 2-fold lower levels of STT3B than the parental Chinese hamster ovary cells. 25792706 3 53 from glycosylation 451:463 arg1 lines 536:540 asparagine-linked glycosylation 6 (ALG6) deficient cell lines 480:540 asparagine-linked glycosylation 6 (ALG6) deficient cell lines that assemble Dol-PP-GlcNAc(2)Man(9) as the largest oligosaccharide donor 480:614 We monitored glycosylation of proteins in asparagine-linked glycosylation 6 (ALG6) deficient cell lines that assemble Dol-PP-GlcNAc(2)Man(9) as the largest oligosaccharide donor. 25792706 3 54 from proteins 468:475 arg1 lines 536:540 asparagine-linked glycosylation 6 (ALG6) deficient cell lines 480:540 asparagine-linked glycosylation 6 (ALG6) deficient cell lines that assemble Dol-PP-GlcNAc(2)Man(9) as the largest oligosaccharide donor 480:614 We monitored glycosylation of proteins in asparagine-linked glycosylation 6 (ALG6) deficient cell lines that assemble Dol-PP-GlcNAc(2)Man(9) as the largest oligosaccharide donor. 25792706 3 55 theme cell 531:534 arg1 lines 536:540 asparagine-linked glycosylation 6 (ALG6) deficient cell lines 480:540 asparagine-linked glycosylation 6 (ALG6) deficient cell lines that assemble Dol-PP-GlcNAc(2)Man(9) as the largest oligosaccharide donor 480:614 We monitored glycosylation of proteins in asparagine-linked glycosylation 6 (ALG6) deficient cell lines that assemble Dol-PP-GlcNAc(2)Man(9) as the largest oligosaccharide donor. 25792706 3 56 dep Man 572:574 arg1 2 570:570 2 570:570 2 570:570 We monitored glycosylation of proteins in asparagine-linked glycosylation 6 (ALG6) deficient cell lines that assemble Dol-PP-GlcNAc(2)Man(9) as the largest oligosaccharide donor. 25792706 3 57 link asparagine-linked 480:496 arg1 glycosylation 498:510 asparagine-linked glycosylation 6 480:512 asparagine-linked glycosylation 6 (ALG6) deficient cell lines that assemble Dol-PP-GlcNAc(2)Man(9) as the largest oligosaccharide donor 480:614 We monitored glycosylation of proteins in asparagine-linked glycosylation 6 (ALG6) deficient cell lines that assemble Dol-PP-GlcNAc(2)Man(9) as the largest oligosaccharide donor. 25792706 3 57 link asparagine-linked 480:496 arg1 ALG6 515:518 ALG6 515:518 ALG6 515:518 We monitored glycosylation of proteins in asparagine-linked glycosylation 6 (ALG6) deficient cell lines that assemble Dol-PP-GlcNAc(2)Man(9) as the largest oligosaccharide donor. 25792706 6 58 theme STT3B 1129:1133 arg1 levels 1119:1124 2-fold lower levels 1106:1124 2-fold lower levels of STT3B 1106:1133 Protein immunoblot analysis and RT-PCR revealed that MI8-5 cells express 2-fold lower levels of STT3B than the parental Chinese hamster ovary cells. 25792706 7 59 dep donor 1286:1290 arg1 3 1283:1283 3 1283:1283 3 1283:1283 The combination of reduced expression of STT3B and the lack of the optimal Dol-PP-GlcNAc(2)Man(9)Glc(3) donor synergize to cause very severe hypoglycosylation of proteins in MI8-5 cells. 25792706 4 60 theme assembled 896:904 arg1 donor 922:926 the fully assembled oligosaccharide donor 886:926 the fully assembled oligosaccharide donor 886:926 Based upon pulse labeling experiments, 30-40% of STT3A-dependent glycosylation sites and 20% of STT3B-dependent sites are skipped in ALG6-congenital disorders of glycosylation fibroblasts supporting previous evidence that the STT3B complex has a relaxed preference for the fully assembled oligosaccharide donor. 25792706 8 61 theme OST 1390:1392 arg1 expression 1402:1411 OST subunit expression 1390:1411 OST subunit expression 1390:1411 Thus, differences in OST subunit expression can modify the severity of hypoglycosylation displayed by cells with a primary defect in the dolichol oligosaccharide assembly pathway. 25792706 7 62 theme severe 1316:1321 arg1 hypoglycosylation 1323:1339 very severe hypoglycosylation 1311:1339 very severe hypoglycosylation of proteins in MI8-5 cells 1311:1366 The combination of reduced expression of STT3B and the lack of the optimal Dol-PP-GlcNAc(2)Man(9)Glc(3) donor synergize to cause very severe hypoglycosylation of proteins in MI8-5 cells. 25792706 4 63 gly glycosylation 682:694 arg2 sites 696:700 STT3A-dependent glycosylation sites 666:700 STT3A-dependent glycosylation sites 666:700 Based upon pulse labeling experiments, 30-40% of STT3A-dependent glycosylation sites and 20% of STT3B-dependent sites are skipped in ALG6-congenital disorders of glycosylation fibroblasts supporting previous evidence that the STT3B complex has a relaxed preference for the fully assembled oligosaccharide donor. 25792706 3 64 theme Dol-PP-GlcNAc 556:568 arg1 donor 610:614 the largest oligosaccharide donor 582:614 the largest oligosaccharide donor 582:614 We monitored glycosylation of proteins in asparagine-linked glycosylation 6 (ALG6) deficient cell lines that assemble Dol-PP-GlcNAc(2)Man(9) as the largest oligosaccharide donor. 25792706 3 64 theme Dol-PP-GlcNAc 556:568 arg1 Man 572:574 Dol-PP-GlcNAc(2)Man(9) 556:577 Dol-PP-GlcNAc(2)Man(9) 556:577 We monitored glycosylation of proteins in asparagine-linked glycosylation 6 (ALG6) deficient cell lines that assemble Dol-PP-GlcNAc(2)Man(9) as the largest oligosaccharide donor. 25792706 2 65 contain have 386:389 arg2 subunits 411:418 different catalytic subunits 391:418 different catalytic subunits (STT3A or STT3B) 391:435 Mammalian cells express two OST complexes that have different catalytic subunits (STT3A or STT3B). 25792706 2 65 contain have 386:389 arg1 complexes 371:379 two OST complexes 363:379 two OST complexes that have different catalytic subunits (STT3A or STT3B) 363:435 Mammalian cells express two OST complexes that have different catalytic subunits (STT3A or STT3B). 25792706 2 65 contain have 386:389 arg2 STT3B 430:434 STT3B 430:434 STT3B 430:434 Mammalian cells express two OST complexes that have different catalytic subunits (STT3A or STT3B). 25792706 2 65 contain have 386:389 arg2 STT3A 421:425 STT3A 421:425 STT3A 421:425 Mammalian cells express two OST complexes that have different catalytic subunits (STT3A or STT3B). 25792706 1 66 gly hypoglycosylation 269:285 arg1 proteins 290:297 proteins 290:297 proteins 290:297 A defect in the assembly of the oligosaccharide donor (Dol-PP-GlcNAc(2)Man(9)Glc(3)) for N-linked glycosylation causes hypoglycosylation of proteins by the oligosaccharyltransferase (OST). 25792706 4 67 theme pulse 628:632 arg1 experiments 643:653 pulse labeling experiments 628:653 pulse labeling experiments 628:653 Based upon pulse labeling experiments, 30-40% of STT3A-dependent glycosylation sites and 20% of STT3B-dependent sites are skipped in ALG6-congenital disorders of glycosylation fibroblasts supporting previous evidence that the STT3B complex has a relaxed preference for the fully assembled oligosaccharide donor. 25792706 7 68 theme reduced 1201:1207 arg1 expression 1209:1218 reduced expression 1201:1218 reduced expression of STT3B 1201:1227 The combination of reduced expression of STT3B and the lack of the optimal Dol-PP-GlcNAc(2)Man(9)Glc(3) donor synergize to cause very severe hypoglycosylation of proteins in MI8-5 cells. 25792706 4 69 contain has 857:859 arg1 complex 849:855 the STT3B complex 839:855 the STT3B complex 839:855 Based upon pulse labeling experiments, 30-40% of STT3A-dependent glycosylation sites and 20% of STT3B-dependent sites are skipped in ALG6-congenital disorders of glycosylation fibroblasts supporting previous evidence that the STT3B complex has a relaxed preference for the fully assembled oligosaccharide donor. 25792706 4 69 contain has 857:859 arg2 preference 871:880 a relaxed preference 861:880 a relaxed preference for the fully assembled oligosaccharide donor 861:926 Based upon pulse labeling experiments, 30-40% of STT3A-dependent glycosylation sites and 20% of STT3B-dependent sites are skipped in ALG6-congenital disorders of glycosylation fibroblasts supporting previous evidence that the STT3B complex has a relaxed preference for the fully assembled oligosaccharide donor. 25792706 8 70 theme hypoglycosylation 1440:1456 arg1 severity 1428:1435 the severity 1424:1435 the severity of hypoglycosylation displayed by cells with a primary defect in the dolichol oligosaccharide assembly pathway 1424:1546 Thus, differences in OST subunit expression can modify the severity of hypoglycosylation displayed by cells with a primary defect in the dolichol oligosaccharide assembly pathway. 25792706 0 71 theme assembled 117:125 arg1 donor 143:147 the fully assembled oligosaccharide donor 107:147 the fully assembled oligosaccharide donor 107:147 Reduced expression of the oligosaccharyltransferase exacerbates protein hypoglycosylation in cells lacking the fully assembled oligosaccharide donor. 25792706 5 72 theme STT3B-dependent 946:960 arg1 sites 962:966 STT3B-dependent sites 946:966 STT3B-dependent sites 946:966 Glycosylation of STT3B-dependent sites was more severely reduced in the ALG6 deficient MI8-5 cell line. 25792706 7 73 theme Glc 1279:1281 arg1 donor 1286:1290 the optimal Dol-PP-GlcNAc(2)Man(9)Glc(3) donor 1245:1290 the optimal Dol-PP-GlcNAc(2)Man(9)Glc(3) donor 1245:1290 The combination of reduced expression of STT3B and the lack of the optimal Dol-PP-GlcNAc(2)Man(9)Glc(3) donor synergize to cause very severe hypoglycosylation of proteins in MI8-5 cells. 25792706 5 74 gly Glycosylation 929:941 arg1 sites 962:966 STT3B-dependent sites 946:966 STT3B-dependent sites 946:966 Glycosylation of STT3B-dependent sites was more severely reduced in the ALG6 deficient MI8-5 cell line. 25792706 5 74 gly Glycosylation 929:941 arg1 line 1027:1030 the ALG6 deficient MI8-5 cell line 997:1030 the ALG6 deficient MI8-5 cell line 997:1030 Glycosylation of STT3B-dependent sites was more severely reduced in the ALG6 deficient MI8-5 cell line. 25792706 4 75 theme STT3B-dependent 713:727 arg1 sites 729:733 STT3B-dependent sites 713:733 STT3B-dependent sites 713:733 Based upon pulse labeling experiments, 30-40% of STT3A-dependent glycosylation sites and 20% of STT3B-dependent sites are skipped in ALG6-congenital disorders of glycosylation fibroblasts supporting previous evidence that the STT3B complex has a relaxed preference for the fully assembled oligosaccharide donor. 25792706 2 76 theme OST 367:369 arg1 complexes 371:379 two OST complexes 363:379 two OST complexes that have different catalytic subunits (STT3A or STT3B) 363:435 Mammalian cells express two OST complexes that have different catalytic subunits (STT3A or STT3B). 25792706 8 77 theme primary 1484:1490 arg1 defect 1492:1497 a primary defect 1482:1497 a primary defect in the dolichol oligosaccharide assembly pathway 1482:1546 Thus, differences in OST subunit expression can modify the severity of hypoglycosylation displayed by cells with a primary defect in the dolichol oligosaccharide assembly pathway. 25792706 4 78 theme glycosylation 682:694 arg1 sites 696:700 STT3A-dependent glycosylation sites 666:700 STT3A-dependent glycosylation sites 666:700 Based upon pulse labeling experiments, 30-40% of STT3A-dependent glycosylation sites and 20% of STT3B-dependent sites are skipped in ALG6-congenital disorders of glycosylation fibroblasts supporting previous evidence that the STT3B complex has a relaxed preference for the fully assembled oligosaccharide donor. 25792706 1 79 theme N-linked 239:246 arg1 glycosylation 248:260 N-linked glycosylation 239:260 N-linked glycosylation 239:260 A defect in the assembly of the oligosaccharide donor (Dol-PP-GlcNAc(2)Man(9)Glc(3)) for N-linked glycosylation causes hypoglycosylation of proteins by the oligosaccharyltransferase (OST). 25792706 6 80 theme immunoblot 1041:1050 arg1 analysis 1052:1059 Protein immunoblot analysis 1033:1059 Protein immunoblot analysis 1033:1059 Protein immunoblot analysis and RT-PCR revealed that MI8-5 cells express 2-fold lower levels of STT3B than the parental Chinese hamster ovary cells. 25792706 3 81 theme largest 586:592 arg1 Man 572:574 Dol-PP-GlcNAc(2)Man(9) 556:577 Dol-PP-GlcNAc(2)Man(9) 556:577 We monitored glycosylation of proteins in asparagine-linked glycosylation 6 (ALG6) deficient cell lines that assemble Dol-PP-GlcNAc(2)Man(9) as the largest oligosaccharide donor. 25792706 3 81 theme largest 586:592 arg1 donor 610:614 the largest oligosaccharide donor 582:614 the largest oligosaccharide donor 582:614 We monitored glycosylation of proteins in asparagine-linked glycosylation 6 (ALG6) deficient cell lines that assemble Dol-PP-GlcNAc(2)Man(9) as the largest oligosaccharide donor. 25792706 2 82 theme different 391:399 arg1 STT3A 421:425 STT3A 421:425 STT3A 421:425 Mammalian cells express two OST complexes that have different catalytic subunits (STT3A or STT3B). 25792706 2 82 theme different 391:399 arg1 subunits 411:418 different catalytic subunits 391:418 different catalytic subunits (STT3A or STT3B) 391:435 Mammalian cells express two OST complexes that have different catalytic subunits (STT3A or STT3B). 25792706 2 82 theme different 391:399 arg1 STT3B 430:434 STT3B 430:434 STT3B 430:434 Mammalian cells express two OST complexes that have different catalytic subunits (STT3A or STT3B). 25792706 5 83 theme ALG6 1001:1004 arg1 line 1027:1030 the ALG6 deficient MI8-5 cell line 997:1030 the ALG6 deficient MI8-5 cell line 997:1030 Glycosylation of STT3B-dependent sites was more severely reduced in the ALG6 deficient MI8-5 cell line. 25792706 8 84 theme dolichol 1506:1513 arg1 pathway 1540:1546 the dolichol oligosaccharide assembly pathway 1502:1546 the dolichol oligosaccharide assembly pathway 1502:1546 Thus, differences in OST subunit expression can modify the severity of hypoglycosylation displayed by cells with a primary defect in the dolichol oligosaccharide assembly pathway. 25792706 5 85 theme MI8-5 1016:1020 arg1 line 1027:1030 the ALG6 deficient MI8-5 cell line 997:1030 the ALG6 deficient MI8-5 cell line 997:1030 Glycosylation of STT3B-dependent sites was more severely reduced in the ALG6 deficient MI8-5 cell line. 25792706 7 86 theme Dol-PP-GlcNAc 1257:1269 arg1 Man 1273:1275 the optimal Dol-PP-GlcNAc(2)Man(9) 1245:1278 the optimal Dol-PP-GlcNAc(2)Man(9)Glc(3) donor 1245:1290 The combination of reduced expression of STT3B and the lack of the optimal Dol-PP-GlcNAc(2)Man(9)Glc(3) donor synergize to cause very severe hypoglycosylation of proteins in MI8-5 cells. 25792706 8 87 theme assembly 1531:1538 arg1 pathway 1540:1546 the dolichol oligosaccharide assembly pathway 1502:1546 the dolichol oligosaccharide assembly pathway 1502:1546 Thus, differences in OST subunit expression can modify the severity of hypoglycosylation displayed by cells with a primary defect in the dolichol oligosaccharide assembly pathway. 25792706 4 88 theme glycosylation 779:791 arg1 fibroblasts 793:803 glycosylation fibroblasts 779:803 glycosylation fibroblasts supporting previous evidence that the STT3B complex has a relaxed preference for the fully assembled oligosaccharide donor 779:926 Based upon pulse labeling experiments, 30-40% of STT3A-dependent glycosylation sites and 20% of STT3B-dependent sites are skipped in ALG6-congenital disorders of glycosylation fibroblasts supporting previous evidence that the STT3B complex has a relaxed preference for the fully assembled oligosaccharide donor. 25792706 3 89 theme proteins 468:475 arg1 glycosylation 451:463 glycosylation 451:463 glycosylation of proteins in asparagine-linked glycosylation 6 (ALG6) deficient cell lines that assemble Dol-PP-GlcNAc(2)Man(9) as the largest oligosaccharide donor 451:614 We monitored glycosylation of proteins in asparagine-linked glycosylation 6 (ALG6) deficient cell lines that assemble Dol-PP-GlcNAc(2)Man(9) as the largest oligosaccharide donor. 25792706 6 90 theme lower 1113:1117 arg1 levels 1119:1124 2-fold lower levels 1106:1124 2-fold lower levels of STT3B 1106:1133 Protein immunoblot analysis and RT-PCR revealed that MI8-5 cells express 2-fold lower levels of STT3B than the parental Chinese hamster ovary cells. 25792706 1 91 dep Man 221:223 arg1 Glc 227:229 Glc(3) 227:232 Dol-PP-GlcNAc(2)Man(9)Glc(3) 205:232 A defect in the assembly of the oligosaccharide donor (Dol-PP-GlcNAc(2)Man(9)Glc(3)) for N-linked glycosylation causes hypoglycosylation of proteins by the oligosaccharyltransferase (OST). 25792706 2 92 theme Mammalian 339:347 arg1 cells 349:353 Mammalian cells 339:353 Mammalian cells 339:353 Mammalian cells express two OST complexes that have different catalytic subunits (STT3A or STT3B). 25081999 1 0 theme domain 154:159 arg1 phosphatases 174:185 RNA polymerase II carboxyl-terminal domain (RNAPII CTD) phosphatases 118:185 RNA polymerase II carboxyl-terminal domain (RNAPII CTD) phosphatases 118:185 RNA polymerase II carboxyl-terminal domain (RNAPII CTD) phosphatases are responsible for the dephosphorylation of the C-terminal domain of the small subunit of RNAPII in eukaryotes. 25081999 1 1 theme domain 247:252 arg1 dephosphorylation 211:227 the dephosphorylation 207:227 the dephosphorylation of the C-terminal domain of the small subunit of RNAPII in eukaryotes 207:297 RNA polymerase II carboxyl-terminal domain (RNAPII CTD) phosphatases are responsible for the dephosphorylation of the C-terminal domain of the small subunit of RNAPII in eukaryotes. 25081999 0 2 theme possible 64:71 arg1 role 73:76 possible role 64:76 possible role of its N-terminal disordered structure 64:115 In vivo putative O-GlcNAcylation of human SCP1 and evidence for possible role of its N-terminal disordered structure. 25081999 5 3 theme liquid 898:903 arg1 spectrometry 925:936 liquid chromatography-mass spectrometry 898:936 liquid chromatography-mass spectrometry analyses 898:945 To gain insight into the PTM of hSCP1, we used the Western blot, immunoprecipitation, succinylayed wheat germ agglutininprecipitation, liquid chromatography-mass spectrometry analyses, and site-directed mutagenesis and identified the Ser41 residue of hSCP1 as the O-GlcNAc modification site. 25081999 3 4 link β-O-linked 637:646 arg1 O-GlcNAc 669:676 O-GlcNAc 669:676 O-GlcNAc 669:676 In this study, using the established cells for inducibly expressing hSCP1 proteins, we monitored the modification of β-O-linked N-acetylglucosamine (O-GlcNAc). 25081999 3 4 link β-O-linked 637:646 arg1 N-acetylglucosamine 648:666 β-O-linked N-acetylglucosamine 637:666 β-O-linked N-acetylglucosamine (O-GlcNAc) 637:677 In this study, using the established cells for inducibly expressing hSCP1 proteins, we monitored the modification of β-O-linked N-acetylglucosamine (O-GlcNAc). 25081999 1 5 from eukaryotes 288:297 arg1 subunit 267:273 the small subunit 257:273 the small subunit of RNAPII in eukaryotes 257:297 RNA polymerase II carboxyl-terminal domain (RNAPII CTD) phosphatases are responsible for the dephosphorylation of the C-terminal domain of the small subunit of RNAPII in eukaryotes. 25081999 6 6 theme protein 1227:1233 arg1 s 1235:1235 the protein(s) 1223:1236 binding the protein(s) 1215:1236 These results suggest that hSCP1 may be an O-GlcNAcylated protein in vivo, and its N-terminus may function a possible role in the PTM, providing a scaffold for binding the protein(s). 25081999 5 7 theme site-directed 952:964 arg1 mutagenesis 966:976 site-directed mutagenesis 952:976 site-directed mutagenesis 952:976 To gain insight into the PTM of hSCP1, we used the Western blot, immunoprecipitation, succinylayed wheat germ agglutininprecipitation, liquid chromatography-mass spectrometry analyses, and site-directed mutagenesis and identified the Ser41 residue of hSCP1 as the O-GlcNAc modification site. 25081999 2 8 theme several 348:354 arg1 partners 368:375 several interacting partners 348:375 several interacting partners with human small CTD phosphatase1 (hSCP1) 348:417 Recently, we demonstrated the identification of several interacting partners with human small CTD phosphatase1 (hSCP1) and the substrate specificity to delineate an appearance of the dephosphorylation catalyzed by SCP1. 25081999 1 9 theme small 261:265 arg1 subunit 267:273 the small subunit 257:273 the small subunit of RNAPII in eukaryotes 257:297 RNA polymerase II carboxyl-terminal domain (RNAPII CTD) phosphatases are responsible for the dephosphorylation of the C-terminal domain of the small subunit of RNAPII in eukaryotes. 25081999 0 10 theme disordered 96:105 arg1 structure 107:115 its N-terminal disordered structure 81:115 its N-terminal disordered structure 81:115 In vivo putative O-GlcNAcylation of human SCP1 and evidence for possible role of its N-terminal disordered structure. 25081999 1 11 from RNAPII 278:283 arg1 eukaryotes 288:297 eukaryotes 288:297 eukaryotes 288:297 RNA polymerase II carboxyl-terminal domain (RNAPII CTD) phosphatases are responsible for the dephosphorylation of the C-terminal domain of the small subunit of RNAPII in eukaryotes. 25081999 5 12 theme Ser41 997:1001 arg1 site 1049:1052 the O-GlcNAc modification site 1023:1052 the O-GlcNAc modification site 1023:1052 To gain insight into the PTM of hSCP1, we used the Western blot, immunoprecipitation, succinylayed wheat germ agglutininprecipitation, liquid chromatography-mass spectrometry analyses, and site-directed mutagenesis and identified the Ser41 residue of hSCP1 as the O-GlcNAc modification site. 25081999 5 12 theme Ser41 997:1001 arg1 hSCP1 1014:1018 hSCP1 1014:1018 hSCP1 1014:1018 To gain insight into the PTM of hSCP1, we used the Western blot, immunoprecipitation, succinylayed wheat germ agglutininprecipitation, liquid chromatography-mass spectrometry analyses, and site-directed mutagenesis and identified the Ser41 residue of hSCP1 as the O-GlcNAc modification site. 25081999 5 12 theme Ser41 997:1001 arg1 residue 1003:1009 the Ser41 residue 993:1009 the Ser41 residue of hSCP1 993:1018 To gain insight into the PTM of hSCP1, we used the Western blot, immunoprecipitation, succinylayed wheat germ agglutininprecipitation, liquid chromatography-mass spectrometry analyses, and site-directed mutagenesis and identified the Ser41 residue of hSCP1 as the O-GlcNAc modification site. 25081999 5 13 theme succinylayed 849:860 arg1 agglutininprecipitation 873:895 succinylayed wheat germ agglutininprecipitation 849:895 succinylayed wheat germ agglutininprecipitation 849:895 To gain insight into the PTM of hSCP1, we used the Western blot, immunoprecipitation, succinylayed wheat germ agglutininprecipitation, liquid chromatography-mass spectrometry analyses, and site-directed mutagenesis and identified the Ser41 residue of hSCP1 as the O-GlcNAc modification site. 25081999 1 14 theme RNAPII 162:167 arg1 domain 154:159 RNA polymerase II carboxyl-terminal domain 118:159 RNA polymerase II carboxyl-terminal domain (RNAPII CTD) phosphatases 118:185 RNA polymerase II carboxyl-terminal domain (RNAPII CTD) phosphatases are responsible for the dephosphorylation of the C-terminal domain of the small subunit of RNAPII in eukaryotes. 25081999 1 14 theme RNAPII 162:167 arg1 CTD 169:171 RNAPII CTD 162:171 RNAPII CTD 162:171 RNA polymerase II carboxyl-terminal domain (RNAPII CTD) phosphatases are responsible for the dephosphorylation of the C-terminal domain of the small subunit of RNAPII in eukaryotes. 25081999 0 15 theme N-terminal 85:94 arg1 structure 107:115 its N-terminal disordered structure 81:115 its N-terminal disordered structure 81:115 In vivo putative O-GlcNAcylation of human SCP1 and evidence for possible role of its N-terminal disordered structure. 25081999 2 16 theme substrate 427:435 arg1 specificity 437:447 the substrate specificity 423:447 the substrate specificity to delineate an appearance of the dephosphorylation catalyzed by SCP1 423:517 Recently, we demonstrated the identification of several interacting partners with human small CTD phosphatase1 (hSCP1) and the substrate specificity to delineate an appearance of the dephosphorylation catalyzed by SCP1. 25081999 6 17 theme O-GlcNAcylated 1098:1111 arg1 protein 1113:1119 an O-GlcNAcylated protein 1095:1119 an O-GlcNAcylated protein 1095:1119 These results suggest that hSCP1 may be an O-GlcNAcylated protein in vivo, and its N-terminus may function a possible role in the PTM, providing a scaffold for binding the protein(s). 25081999 6 17 theme O-GlcNAcylated 1098:1111 arg1 hSCP1 1082:1086 hSCP1 1082:1086 hSCP1 1082:1086 These results suggest that hSCP1 may be an O-GlcNAcylated protein in vivo, and its N-terminus may function a possible role in the PTM, providing a scaffold for binding the protein(s). 25081999 2 18 theme small 388:392 arg1 hSCP1 412:416 hSCP1 412:416 hSCP1 412:416 Recently, we demonstrated the identification of several interacting partners with human small CTD phosphatase1 (hSCP1) and the substrate specificity to delineate an appearance of the dephosphorylation catalyzed by SCP1. 25081999 2 18 theme small 388:392 arg1 phosphatase1 398:409 human small CTD phosphatase1 382:409 human small CTD phosphatase1 (hSCP1) 382:417 Recently, we demonstrated the identification of several interacting partners with human small CTD phosphatase1 (hSCP1) and the substrate specificity to delineate an appearance of the dephosphorylation catalyzed by SCP1. 25081999 5 19 theme hSCP1 795:799 arg1 PTM 788:790 the PTM 784:790 the PTM of hSCP1 784:799 To gain insight into the PTM of hSCP1, we used the Western blot, immunoprecipitation, succinylayed wheat germ agglutininprecipitation, liquid chromatography-mass spectrometry analyses, and site-directed mutagenesis and identified the Ser41 residue of hSCP1 as the O-GlcNAc modification site. 25081999 1 20 from subunit 267:273 arg1 eukaryotes 288:297 eukaryotes 288:297 eukaryotes 288:297 RNA polymerase II carboxyl-terminal domain (RNAPII CTD) phosphatases are responsible for the dephosphorylation of the C-terminal domain of the small subunit of RNAPII in eukaryotes. 25081999 6 21 theme possible 1164:1171 arg1 role 1173:1176 a possible role 1162:1176 a possible role 1162:1176 These results suggest that hSCP1 may be an O-GlcNAcylated protein in vivo, and its N-terminus may function a possible role in the PTM, providing a scaffold for binding the protein(s). 25081999 2 22 theme human 382:386 arg1 hSCP1 412:416 hSCP1 412:416 hSCP1 412:416 Recently, we demonstrated the identification of several interacting partners with human small CTD phosphatase1 (hSCP1) and the substrate specificity to delineate an appearance of the dephosphorylation catalyzed by SCP1. 25081999 2 22 theme human 382:386 arg1 phosphatase1 398:409 human small CTD phosphatase1 382:409 human small CTD phosphatase1 (hSCP1) 382:417 Recently, we demonstrated the identification of several interacting partners with human small CTD phosphatase1 (hSCP1) and the substrate specificity to delineate an appearance of the dephosphorylation catalyzed by SCP1. 25081999 0 23 theme In 0:1 arg1 O-GlcNAcylation 17:31 In vivo putative O-GlcNAcylation 0:31 In vivo putative O-GlcNAcylation of human SCP1 0:45 In vivo putative O-GlcNAcylation of human SCP1 and evidence for possible role of its N-terminal disordered structure. 25081999 1 24 theme subunit 267:273 arg1 subunit 267:273 the small subunit 257:273 the small subunit of RNAPII in eukaryotes 257:297 RNA polymerase II carboxyl-terminal domain (RNAPII CTD) phosphatases are responsible for the dephosphorylation of the C-terminal domain of the small subunit of RNAPII in eukaryotes. 25081999 1 24 theme subunit 267:273 arg1 domain 247:252 the C-terminal domain 232:252 the C-terminal domain of the small subunit of RNAPII in eukaryotes 232:297 RNA polymerase II carboxyl-terminal domain (RNAPII CTD) phosphatases are responsible for the dephosphorylation of the C-terminal domain of the small subunit of RNAPII in eukaryotes. 25081999 4 25 theme common 715:720 arg1 PTMs 756:759 PTMs 756:759 PTMs 756:759 O-GlcNAcylation is one of the most common post-translational modifications (PTMs). 25081999 4 25 theme common 715:720 arg1 modifications 741:753 the most common post-translational modifications 706:753 the most common post-translational modifications (PTMs) 706:760 O-GlcNAcylation is one of the most common post-translational modifications (PTMs). 25081999 4 26 theme modifications 741:753 arg1 one 699:701 one 699:701 one 699:701 O-GlcNAcylation is one of the most common post-translational modifications (PTMs). 25081999 4 26 theme modifications 741:753 arg1 PTMs 756:759 PTMs 756:759 PTMs 756:759 O-GlcNAcylation is one of the most common post-translational modifications (PTMs). 25081999 4 26 theme modifications 741:753 arg1 modifications 741:753 the most common post-translational modifications 706:753 the most common post-translational modifications (PTMs) 706:760 O-GlcNAcylation is one of the most common post-translational modifications (PTMs). 25081999 5 27 theme wheat 862:866 arg1 agglutininprecipitation 873:895 succinylayed wheat germ agglutininprecipitation 849:895 succinylayed wheat germ agglutininprecipitation 849:895 To gain insight into the PTM of hSCP1, we used the Western blot, immunoprecipitation, succinylayed wheat germ agglutininprecipitation, liquid chromatography-mass spectrometry analyses, and site-directed mutagenesis and identified the Ser41 residue of hSCP1 as the O-GlcNAc modification site. 25081999 2 28 theme interacting 356:366 arg1 partners 368:375 several interacting partners 348:375 several interacting partners with human small CTD phosphatase1 (hSCP1) 348:417 Recently, we demonstrated the identification of several interacting partners with human small CTD phosphatase1 (hSCP1) and the substrate specificity to delineate an appearance of the dephosphorylation catalyzed by SCP1. 25081999 5 29 theme O-GlcNAc 1027:1034 arg1 site 1049:1052 the O-GlcNAc modification site 1023:1052 the O-GlcNAc modification site 1023:1052 To gain insight into the PTM of hSCP1, we used the Western blot, immunoprecipitation, succinylayed wheat germ agglutininprecipitation, liquid chromatography-mass spectrometry analyses, and site-directed mutagenesis and identified the Ser41 residue of hSCP1 as the O-GlcNAc modification site. 25081999 5 29 theme O-GlcNAc 1027:1034 arg1 hSCP1 1014:1018 hSCP1 1014:1018 hSCP1 1014:1018 To gain insight into the PTM of hSCP1, we used the Western blot, immunoprecipitation, succinylayed wheat germ agglutininprecipitation, liquid chromatography-mass spectrometry analyses, and site-directed mutagenesis and identified the Ser41 residue of hSCP1 as the O-GlcNAc modification site. 25081999 5 29 theme O-GlcNAc 1027:1034 arg1 residue 1003:1009 the Ser41 residue 993:1009 the Ser41 residue of hSCP1 993:1018 To gain insight into the PTM of hSCP1, we used the Western blot, immunoprecipitation, succinylayed wheat germ agglutininprecipitation, liquid chromatography-mass spectrometry analyses, and site-directed mutagenesis and identified the Ser41 residue of hSCP1 as the O-GlcNAc modification site. 25081999 0 30 theme putative 8:15 arg1 O-GlcNAcylation 17:31 In vivo putative O-GlcNAcylation 0:31 In vivo putative O-GlcNAcylation of human SCP1 0:45 In vivo putative O-GlcNAcylation of human SCP1 and evidence for possible role of its N-terminal disordered structure. 25081999 1 31 theme RNAPII 278:283 arg1 subunit 267:273 the small subunit 257:273 the small subunit of RNAPII in eukaryotes 257:297 RNA polymerase II carboxyl-terminal domain (RNAPII CTD) phosphatases are responsible for the dephosphorylation of the C-terminal domain of the small subunit of RNAPII in eukaryotes. 25081999 0 32 theme structure 107:115 arg1 role 73:76 possible role 64:76 possible role of its N-terminal disordered structure 64:115 In vivo putative O-GlcNAcylation of human SCP1 and evidence for possible role of its N-terminal disordered structure. 25081999 3 33 theme β-O-linked 637:646 arg1 O-GlcNAc 669:676 O-GlcNAc 669:676 O-GlcNAc 669:676 In this study, using the established cells for inducibly expressing hSCP1 proteins, we monitored the modification of β-O-linked N-acetylglucosamine (O-GlcNAc). 25081999 3 33 theme β-O-linked 637:646 arg1 N-acetylglucosamine 648:666 β-O-linked N-acetylglucosamine 637:666 β-O-linked N-acetylglucosamine (O-GlcNAc) 637:677 In this study, using the established cells for inducibly expressing hSCP1 proteins, we monitored the modification of β-O-linked N-acetylglucosamine (O-GlcNAc). 25081999 3 34 theme established 545:555 arg1 cells 557:561 the established cells 541:561 the established cells for inducibly expressing hSCP1 proteins 541:601 In this study, using the established cells for inducibly expressing hSCP1 proteins, we monitored the modification of β-O-linked N-acetylglucosamine (O-GlcNAc). 25081999 5 35 theme Western 814:820 arg1 blot 822:825 Western blot 814:825 Western blot 814:825 To gain insight into the PTM of hSCP1, we used the Western blot, immunoprecipitation, succinylayed wheat germ agglutininprecipitation, liquid chromatography-mass spectrometry analyses, and site-directed mutagenesis and identified the Ser41 residue of hSCP1 as the O-GlcNAc modification site. 25081999 0 36 theme human 36:40 arg1 SCP1 42:45 human SCP1 36:45 human SCP1 36:45 In vivo putative O-GlcNAcylation of human SCP1 and evidence for possible role of its N-terminal disordered structure. 25081999 3 37 theme N-acetylglucosamine 648:666 arg1 modification 621:632 the modification 617:632 the modification of β-O-linked N-acetylglucosamine (O-GlcNAc) 617:677 In this study, using the established cells for inducibly expressing hSCP1 proteins, we monitored the modification of β-O-linked N-acetylglucosamine (O-GlcNAc). 25081999 3 38 theme hSCP1 588:592 arg1 proteins 594:601 inducibly expressing hSCP1 proteins 567:601 inducibly expressing hSCP1 proteins 567:601 In this study, using the established cells for inducibly expressing hSCP1 proteins, we monitored the modification of β-O-linked N-acetylglucosamine (O-GlcNAc). 25081999 2 39 theme CTD 394:396 arg1 hSCP1 412:416 hSCP1 412:416 hSCP1 412:416 Recently, we demonstrated the identification of several interacting partners with human small CTD phosphatase1 (hSCP1) and the substrate specificity to delineate an appearance of the dephosphorylation catalyzed by SCP1. 25081999 2 39 theme CTD 394:396 arg1 phosphatase1 398:409 human small CTD phosphatase1 382:409 human small CTD phosphatase1 (hSCP1) 382:417 Recently, we demonstrated the identification of several interacting partners with human small CTD phosphatase1 (hSCP1) and the substrate specificity to delineate an appearance of the dephosphorylation catalyzed by SCP1. 25081999 5 40 theme modification 1036:1047 arg1 site 1049:1052 the O-GlcNAc modification site 1023:1052 the O-GlcNAc modification site 1023:1052 To gain insight into the PTM of hSCP1, we used the Western blot, immunoprecipitation, succinylayed wheat germ agglutininprecipitation, liquid chromatography-mass spectrometry analyses, and site-directed mutagenesis and identified the Ser41 residue of hSCP1 as the O-GlcNAc modification site. 25081999 5 40 theme modification 1036:1047 arg1 hSCP1 1014:1018 hSCP1 1014:1018 hSCP1 1014:1018 To gain insight into the PTM of hSCP1, we used the Western blot, immunoprecipitation, succinylayed wheat germ agglutininprecipitation, liquid chromatography-mass spectrometry analyses, and site-directed mutagenesis and identified the Ser41 residue of hSCP1 as the O-GlcNAc modification site. 25081999 5 40 theme modification 1036:1047 arg1 residue 1003:1009 the Ser41 residue 993:1009 the Ser41 residue of hSCP1 993:1018 To gain insight into the PTM of hSCP1, we used the Western blot, immunoprecipitation, succinylayed wheat germ agglutininprecipitation, liquid chromatography-mass spectrometry analyses, and site-directed mutagenesis and identified the Ser41 residue of hSCP1 as the O-GlcNAc modification site. 25081999 5 41 theme germ 868:871 arg1 agglutininprecipitation 873:895 succinylayed wheat germ agglutininprecipitation 849:895 succinylayed wheat germ agglutininprecipitation 849:895 To gain insight into the PTM of hSCP1, we used the Western blot, immunoprecipitation, succinylayed wheat germ agglutininprecipitation, liquid chromatography-mass spectrometry analyses, and site-directed mutagenesis and identified the Ser41 residue of hSCP1 as the O-GlcNAc modification site. 25081999 5 42 used used 805:808 arg2 we 802:803 we 802:803 we 802:803 To gain insight into the PTM of hSCP1, we used the Western blot, immunoprecipitation, succinylayed wheat germ agglutininprecipitation, liquid chromatography-mass spectrometry analyses, and site-directed mutagenesis and identified the Ser41 residue of hSCP1 as the O-GlcNAc modification site. 25081999 6 43 theme binding 1215:1221 arg1 s 1235:1235 the protein(s) 1223:1236 binding the protein(s) 1215:1236 These results suggest that hSCP1 may be an O-GlcNAcylated protein in vivo, and its N-terminus may function a possible role in the PTM, providing a scaffold for binding the protein(s). 25081999 5 44 theme chromatography-mass 905:923 arg1 spectrometry 925:936 liquid chromatography-mass spectrometry 898:936 liquid chromatography-mass spectrometry analyses 898:945 To gain insight into the PTM of hSCP1, we used the Western blot, immunoprecipitation, succinylayed wheat germ agglutininprecipitation, liquid chromatography-mass spectrometry analyses, and site-directed mutagenesis and identified the Ser41 residue of hSCP1 as the O-GlcNAc modification site. 25081999 0 45 theme SCP1 42:45 arg1 evidence 51:58 evidence 51:58 evidence for possible role of its N-terminal disordered structure 51:115 In vivo putative O-GlcNAcylation of human SCP1 and evidence for possible role of its N-terminal disordered structure. 25081999 0 45 theme SCP1 42:45 arg1 O-GlcNAcylation 17:31 In vivo putative O-GlcNAcylation 0:31 In vivo putative O-GlcNAcylation of human SCP1 0:45 In vivo putative O-GlcNAcylation of human SCP1 and evidence for possible role of its N-terminal disordered structure. 25081999 3 46 theme expressing 577:586 arg1 proteins 594:601 inducibly expressing hSCP1 proteins 567:601 inducibly expressing hSCP1 proteins 567:601 In this study, using the established cells for inducibly expressing hSCP1 proteins, we monitored the modification of β-O-linked N-acetylglucosamine (O-GlcNAc). 25081999 5 47 theme spectrometry 925:936 arg1 analyses 938:945 liquid chromatography-mass spectrometry analyses 898:945 liquid chromatography-mass spectrometry analyses 898:945 To gain insight into the PTM of hSCP1, we used the Western blot, immunoprecipitation, succinylayed wheat germ agglutininprecipitation, liquid chromatography-mass spectrometry analyses, and site-directed mutagenesis and identified the Ser41 residue of hSCP1 as the O-GlcNAc modification site. 25081999 1 48 theme RNA 118:120 arg1 domain 154:159 RNA polymerase II carboxyl-terminal domain 118:159 RNA polymerase II carboxyl-terminal domain (RNAPII CTD) phosphatases 118:185 RNA polymerase II carboxyl-terminal domain (RNAPII CTD) phosphatases are responsible for the dephosphorylation of the C-terminal domain of the small subunit of RNAPII in eukaryotes. 25081999 1 48 theme RNA 118:120 arg1 CTD 169:171 RNAPII CTD 162:171 RNAPII CTD 162:171 RNA polymerase II carboxyl-terminal domain (RNAPII CTD) phosphatases are responsible for the dephosphorylation of the C-terminal domain of the small subunit of RNAPII in eukaryotes. 25081999 2 49 with partners 368:375 arg1 hSCP1 412:416 hSCP1 412:416 hSCP1 412:416 Recently, we demonstrated the identification of several interacting partners with human small CTD phosphatase1 (hSCP1) and the substrate specificity to delineate an appearance of the dephosphorylation catalyzed by SCP1. 25081999 2 49 with partners 368:375 arg1 phosphatase1 398:409 human small CTD phosphatase1 382:409 human small CTD phosphatase1 (hSCP1) 382:417 Recently, we demonstrated the identification of several interacting partners with human small CTD phosphatase1 (hSCP1) and the substrate specificity to delineate an appearance of the dephosphorylation catalyzed by SCP1. 25081999 5 50 theme hSCP1 1014:1018 arg1 site 1049:1052 the O-GlcNAc modification site 1023:1052 the O-GlcNAc modification site 1023:1052 To gain insight into the PTM of hSCP1, we used the Western blot, immunoprecipitation, succinylayed wheat germ agglutininprecipitation, liquid chromatography-mass spectrometry analyses, and site-directed mutagenesis and identified the Ser41 residue of hSCP1 as the O-GlcNAc modification site. 25081999 5 50 theme hSCP1 1014:1018 arg1 hSCP1 1014:1018 hSCP1 1014:1018 hSCP1 1014:1018 To gain insight into the PTM of hSCP1, we used the Western blot, immunoprecipitation, succinylayed wheat germ agglutininprecipitation, liquid chromatography-mass spectrometry analyses, and site-directed mutagenesis and identified the Ser41 residue of hSCP1 as the O-GlcNAc modification site. 25081999 5 50 theme hSCP1 1014:1018 arg1 residue 1003:1009 the Ser41 residue 993:1009 the Ser41 residue of hSCP1 993:1018 To gain insight into the PTM of hSCP1, we used the Western blot, immunoprecipitation, succinylayed wheat germ agglutininprecipitation, liquid chromatography-mass spectrometry analyses, and site-directed mutagenesis and identified the Ser41 residue of hSCP1 as the O-GlcNAc modification site. 25081999 1 51 theme polymerase 122:131 arg1 domain 154:159 RNA polymerase II carboxyl-terminal domain 118:159 RNA polymerase II carboxyl-terminal domain (RNAPII CTD) phosphatases 118:185 RNA polymerase II carboxyl-terminal domain (RNAPII CTD) phosphatases are responsible for the dephosphorylation of the C-terminal domain of the small subunit of RNAPII in eukaryotes. 25081999 1 51 theme polymerase 122:131 arg1 CTD 169:171 RNAPII CTD 162:171 RNAPII CTD 162:171 RNA polymerase II carboxyl-terminal domain (RNAPII CTD) phosphatases are responsible for the dephosphorylation of the C-terminal domain of the small subunit of RNAPII in eukaryotes. 25081999 4 52 theme post-translational 722:739 arg1 PTMs 756:759 PTMs 756:759 PTMs 756:759 O-GlcNAcylation is one of the most common post-translational modifications (PTMs). 25081999 4 52 theme post-translational 722:739 arg1 modifications 741:753 the most common post-translational modifications 706:753 the most common post-translational modifications (PTMs) 706:760 O-GlcNAcylation is one of the most common post-translational modifications (PTMs). 25081999 2 53 theme partners 368:375 arg1 specificity 437:447 the substrate specificity 423:447 the substrate specificity to delineate an appearance of the dephosphorylation catalyzed by SCP1 423:517 Recently, we demonstrated the identification of several interacting partners with human small CTD phosphatase1 (hSCP1) and the substrate specificity to delineate an appearance of the dephosphorylation catalyzed by SCP1. 25081999 2 53 theme partners 368:375 arg1 identification 330:343 the identification 326:343 the identification of several interacting partners with human small CTD phosphatase1 (hSCP1) 326:417 Recently, we demonstrated the identification of several interacting partners with human small CTD phosphatase1 (hSCP1) and the substrate specificity to delineate an appearance of the dephosphorylation catalyzed by SCP1. 25081999 2 54 theme dephosphorylation 483:499 arg1 appearance 465:474 an appearance 462:474 an appearance of the dephosphorylation catalyzed by SCP1 462:517 Recently, we demonstrated the identification of several interacting partners with human small CTD phosphatase1 (hSCP1) and the substrate specificity to delineate an appearance of the dephosphorylation catalyzed by SCP1. 25081999 0 55 dep In 0:1 arg1 vivo 3:6 vivo 3:6 vivo 3:6 In vivo putative O-GlcNAcylation of human SCP1 and evidence for possible role of its N-terminal disordered structure. 25081999 1 56 theme carboxyl-terminal 136:152 arg1 domain 154:159 RNA polymerase II carboxyl-terminal domain 118:159 RNA polymerase II carboxyl-terminal domain (RNAPII CTD) phosphatases 118:185 RNA polymerase II carboxyl-terminal domain (RNAPII CTD) phosphatases are responsible for the dephosphorylation of the C-terminal domain of the small subunit of RNAPII in eukaryotes. 25081999 1 56 theme carboxyl-terminal 136:152 arg1 CTD 169:171 RNAPII CTD 162:171 RNAPII CTD 162:171 RNA polymerase II carboxyl-terminal domain (RNAPII CTD) phosphatases are responsible for the dephosphorylation of the C-terminal domain of the small subunit of RNAPII in eukaryotes. 25081999 1 57 theme C-terminal 236:245 arg1 subunit 267:273 the small subunit 257:273 the small subunit of RNAPII in eukaryotes 257:297 RNA polymerase II carboxyl-terminal domain (RNAPII CTD) phosphatases are responsible for the dephosphorylation of the C-terminal domain of the small subunit of RNAPII in eukaryotes. 25081999 1 57 theme C-terminal 236:245 arg1 domain 247:252 the C-terminal domain 232:252 the C-terminal domain of the small subunit of RNAPII in eukaryotes 232:297 RNA polymerase II carboxyl-terminal domain (RNAPII CTD) phosphatases are responsible for the dephosphorylation of the C-terminal domain of the small subunit of RNAPII in eukaryotes. 24526702 6 0 dep O-GlcNAcylation 1041:1055 arg1 either 1058:1063 either 1058:1063 either 1058:1063 Increased O-GlcNAcylation, either by Thiamet-G or O-GlcNAcase knockdown, promoted calcification of primary mouse vascular smooth muscle cells. 24526702 4 1 from compliance 785:794 arg1 mice 799:802 mice 799:802 mice 799:802 METHODS AND RESULTS: Low-dose streptozotocin-induced diabetic mice exhibited increased aortic O-GlcNAcylation and vascular calcification, which was also associated with impaired aortic compliance in mice. 24526702 6 2 theme Increased 1031:1039 arg1 O-GlcNAcylation 1041:1055 Increased O-GlcNAcylation 1031:1055 Increased O-GlcNAcylation 1031:1055 Increased O-GlcNAcylation, either by Thiamet-G or O-GlcNAcase knockdown, promoted calcification of primary mouse vascular smooth muscle cells. 24526702 4 3 theme increased 677:685 arg1 O-GlcNAcylation 694:708 increased aortic O-GlcNAcylation 677:708 increased aortic O-GlcNAcylation 677:708 METHODS AND RESULTS: Low-dose streptozotocin-induced diabetic mice exhibited increased aortic O-GlcNAcylation and vascular calcification, which was also associated with impaired aortic compliance in mice. 24526702 2 4 theme mellitus 310:317 arg1 Hyperglycemia 272:284 Hyperglycemia 272:284 Hyperglycemia 272:284 Hyperglycemia, a hallmark of diabetes mellitus, is associated with increased vascular calcification and increased modification of proteins by O-linked N-acetylglucosamine (O-GlcNAcylation). 24526702 2 4 theme mellitus 310:317 arg1 hallmark 289:296 a hallmark 287:296 a hallmark of diabetes mellitus 287:317 Hyperglycemia, a hallmark of diabetes mellitus, is associated with increased vascular calcification and increased modification of proteins by O-linked N-acetylglucosamine (O-GlcNAcylation). 24526702 8 5 theme new 1411:1413 arg1 sites 1415:1419 two new sites 1407:1419 two new sites 1407:1419 O-GlcNAcylation of AKT at two new sites, T430 and T479, promoted AKT phosphorylation, which in turn enhanced vascular smooth muscle cell calcification. 24526702 8 5 theme new 1411:1413 arg1 T479 1431:1434 T479 1431:1434 T479 1431:1434 O-GlcNAcylation of AKT at two new sites, T430 and T479, promoted AKT phosphorylation, which in turn enhanced vascular smooth muscle cell calcification. 24526702 8 5 theme new 1411:1413 arg1 T430 1422:1425 T430 1422:1425 T430 1422:1425 O-GlcNAcylation of AKT at two new sites, T430 and T479, promoted AKT phosphorylation, which in turn enhanced vascular smooth muscle cell calcification. 24526702 7 6 theme smooth 1262:1267 arg1 cell 1276:1279 the O-GlcNAcase knockdown vascular smooth muscle cell 1227:1279 the O-GlcNAcase knockdown vascular smooth muscle cell 1227:1279 Increased O-GlcNAcylation in diabetic arteries or in the O-GlcNAcase knockdown vascular smooth muscle cell upregulated expression of the osteogenic transcription factor Runx2 and enhanced activation of AKT. 24526702 10 7 theme vascular 1914:1921 arg1 calcification 1923:1935 vascular calcification 1914:1935 vascular calcification 1914:1935 CONCLUSIONS: O-GlcNAcylation of AKT at 2 new sites enhanced AKT phosphorylation and activation, thus promoting vascular calcification. 24526702 4 8 theme impaired 769:776 arg1 compliance 785:794 impaired aortic compliance 769:794 impaired aortic compliance in mice 769:802 METHODS AND RESULTS: Low-dose streptozotocin-induced diabetic mice exhibited increased aortic O-GlcNAcylation and vascular calcification, which was also associated with impaired aortic compliance in mice. 24526702 7 9 theme knockdown 1243:1251 arg1 cell 1276:1279 the O-GlcNAcase knockdown vascular smooth muscle cell 1227:1279 the O-GlcNAcase knockdown vascular smooth muscle cell 1227:1279 Increased O-GlcNAcylation in diabetic arteries or in the O-GlcNAcase knockdown vascular smooth muscle cell upregulated expression of the osteogenic transcription factor Runx2 and enhanced activation of AKT. 24526702 5 10 theme diabetic 1008:1015 arg1 mice 1017:1020 diabetic mice 1008:1020 diabetic mice 1008:1020 Elevation of O-GlcNAcylation by administration of Thiamet-G, a potent inhibitor for O-GlcNAcase that removes O-GlcNAcylation, further accelerated vascular calcification and worsened aortic compliance of diabetic mice in vivo. 24526702 0 11 link O-linked 21:28 arg1 N-acetylglucosamine 30:48 O-linked N-acetylglucosamine 21:48 O-linked N-acetylglucosamine 21:48 Activation of AKT by O-linked N-acetylglucosamine induces vascular calcification in diabetes mellitus. 24526702 11 12 theme novel 1968:1972 arg1 effect 1984:1989 a novel causative effect 1966:1989 a novel causative effect of O-GlcNAcylation in regulating vascular calcification in diabetes mellitus 1966:2066 Our studies have identified a novel causative effect of O-GlcNAcylation in regulating vascular calcification in diabetes mellitus and uncovered a key molecular mechanism underlying O-GlcNAcylation-mediated activation of AKT. 24526702 11 13 theme key 2084:2086 arg1 mechanism 2098:2106 a key molecular mechanism 2082:2106 a key molecular mechanism underlying O-GlcNAcylation-mediated activation of AKT 2082:2160 Our studies have identified a novel causative effect of O-GlcNAcylation in regulating vascular calcification in diabetes mellitus and uncovered a key molecular mechanism underlying O-GlcNAcylation-mediated activation of AKT. 24526702 5 14 theme O-GlcNAcylation 818:832 arg1 Elevation 805:813 Elevation 805:813 Elevation of O-GlcNAcylation by administration of Thiamet-G, a potent inhibitor for O-GlcNAcase that removes O-GlcNAcylation, 805:929 Elevation of O-GlcNAcylation by administration of Thiamet-G, a potent inhibitor for O-GlcNAcase that removes O-GlcNAcylation, further accelerated vascular calcification and worsened aortic compliance of diabetic mice in vivo. 24526702 1 15 theme patients 239:246 arg1 mortality 226:234 mortality 226:234 mortality 226:234 RATIONALE: Vascular calcification is a serious cardiovascular complication that contributes to the increased morbidity and mortality of patients with diabetes mellitus. 24526702 1 15 theme patients 239:246 arg1 morbidity 212:220 morbidity 212:220 morbidity 212:220 RATIONALE: Vascular calcification is a serious cardiovascular complication that contributes to the increased morbidity and mortality of patients with diabetes mellitus. 24526702 8 16 theme AKT 1446:1448 arg1 phosphorylation 1450:1464 AKT phosphorylation 1446:1464 AKT phosphorylation 1446:1464 O-GlcNAcylation of AKT at two new sites, T430 and T479, promoted AKT phosphorylation, which in turn enhanced vascular smooth muscle cell calcification. 24526702 11 17 theme O-GlcNAcylation 1994:2008 arg1 effect 1984:1989 a novel causative effect 1966:1989 a novel causative effect of O-GlcNAcylation in regulating vascular calcification in diabetes mellitus 1966:2066 Our studies have identified a novel causative effect of O-GlcNAcylation in regulating vascular calcification in diabetes mellitus and uncovered a key molecular mechanism underlying O-GlcNAcylation-mediated activation of AKT. 24526702 7 18 theme diabetic 1203:1210 arg1 arteries 1212:1219 diabetic arteries 1203:1219 diabetic arteries 1203:1219 Increased O-GlcNAcylation in diabetic arteries or in the O-GlcNAcase knockdown vascular smooth muscle cell upregulated expression of the osteogenic transcription factor Runx2 and enhanced activation of AKT. 24526702 9 19 theme target 1673:1678 arg1 phosphorylation 1617:1631 phosphorylation 1617:1631 phosphorylation of AKT at S473 1617:1646 Site-directed mutation of AKT at T430 and T479 decreased O-GlcNAcylation, inhibited phosphorylation of AKT at S473 and binding of mammalian target of rapamycin complex 2 to AKT, and subsequently blocked Runx2 transactivity and vascular smooth muscle cell calcification. 24526702 9 19 theme target 1673:1678 arg1 binding 1652:1658 binding 1652:1658 binding of mammalian target of rapamycin complex 2 to AKT 1652:1708 Site-directed mutation of AKT at T430 and T479 decreased O-GlcNAcylation, inhibited phosphorylation of AKT at S473 and binding of mammalian target of rapamycin complex 2 to AKT, and subsequently blocked Runx2 transactivity and vascular smooth muscle cell calcification. 24526702 6 20 theme cells 1167:1171 arg1 calcification 1113:1125 calcification 1113:1125 calcification of primary mouse vascular smooth muscle cells 1113:1171 Increased O-GlcNAcylation, either by Thiamet-G or O-GlcNAcase knockdown, promoted calcification of primary mouse vascular smooth muscle cells. 24526702 7 21 theme Runx2 1343:1347 arg1 expression 1293:1302 expression 1293:1302 expression of the osteogenic transcription factor Runx2 1293:1347 Increased O-GlcNAcylation in diabetic arteries or in the O-GlcNAcase knockdown vascular smooth muscle cell upregulated expression of the osteogenic transcription factor Runx2 and enhanced activation of AKT. 24526702 9 22 theme rapamycin 1683:1691 arg1 complex 1693:1699 rapamycin complex 2 1683:1701 rapamycin complex 2 1683:1701 Site-directed mutation of AKT at T430 and T479 decreased O-GlcNAcylation, inhibited phosphorylation of AKT at S473 and binding of mammalian target of rapamycin complex 2 to AKT, and subsequently blocked Runx2 transactivity and vascular smooth muscle cell calcification. 24526702 6 23 theme smooth 1153:1158 arg1 cells 1167:1171 primary mouse vascular smooth muscle cells 1130:1171 primary mouse vascular smooth muscle cells 1130:1171 Increased O-GlcNAcylation, either by Thiamet-G or O-GlcNAcase knockdown, promoted calcification of primary mouse vascular smooth muscle cells. 24526702 0 24 theme diabetes 84:91 arg1 mellitus 93:100 diabetes mellitus 84:100 diabetes mellitus 84:100 Activation of AKT by O-linked N-acetylglucosamine induces vascular calcification in diabetes mellitus. 24526702 7 25 from O-GlcNAcylation 1184:1198 arg1 cell 1276:1279 the O-GlcNAcase knockdown vascular smooth muscle cell 1227:1279 the O-GlcNAcase knockdown vascular smooth muscle cell 1227:1279 Increased O-GlcNAcylation in diabetic arteries or in the O-GlcNAcase knockdown vascular smooth muscle cell upregulated expression of the osteogenic transcription factor Runx2 and enhanced activation of AKT. 24526702 7 25 from O-GlcNAcylation 1184:1198 arg1 arteries 1212:1219 diabetic arteries 1203:1219 diabetic arteries 1203:1219 Increased O-GlcNAcylation in diabetic arteries or in the O-GlcNAcase knockdown vascular smooth muscle cell upregulated expression of the osteogenic transcription factor Runx2 and enhanced activation of AKT. 24526702 6 26 theme mouse 1138:1142 arg1 cells 1167:1171 primary mouse vascular smooth muscle cells 1130:1171 primary mouse vascular smooth muscle cells 1130:1171 Increased O-GlcNAcylation, either by Thiamet-G or O-GlcNAcase knockdown, promoted calcification of primary mouse vascular smooth muscle cells. 24526702 8 27 theme smooth 1499:1504 arg1 calcification 1518:1530 vascular smooth muscle cell calcification 1490:1530 vascular smooth muscle cell calcification 1490:1530 O-GlcNAcylation of AKT at two new sites, T430 and T479, promoted AKT phosphorylation, which in turn enhanced vascular smooth muscle cell calcification. 24526702 1 28 theme serious 142:148 arg1 complication 165:176 a serious cardiovascular complication 140:176 a serious cardiovascular complication that contributes to the increased morbidity and mortality of patients with diabetes mellitus 140:269 RATIONALE: Vascular calcification is a serious cardiovascular complication that contributes to the increased morbidity and mortality of patients with diabetes mellitus. 24526702 1 28 theme serious 142:148 arg1 RATIONALE 103:111 RATIONALE 103:111 RATIONALE: Vascular calcification 103:135 RATIONALE: Vascular calcification is a serious cardiovascular complication that contributes to the increased morbidity and mortality of patients with diabetes mellitus. 24526702 10 29 theme new 1844:1846 arg1 sites 1848:1852 2 new sites 1842:1852 2 new sites 1842:1852 CONCLUSIONS: O-GlcNAcylation of AKT at 2 new sites enhanced AKT phosphorylation and activation, thus promoting vascular calcification. 24526702 8 30 theme cell 1513:1516 arg1 calcification 1518:1530 vascular smooth muscle cell calcification 1490:1530 vascular smooth muscle cell calcification 1490:1530 O-GlcNAcylation of AKT at two new sites, T430 and T479, promoted AKT phosphorylation, which in turn enhanced vascular smooth muscle cell calcification. 24526702 10 31 theme AKT 1835:1837 arg1 O-GlcNAcylation 1816:1830 O-GlcNAcylation 1816:1830 O-GlcNAcylation of AKT at 2 new sites 1816:1852 CONCLUSIONS: O-GlcNAcylation of AKT at 2 new sites enhanced AKT phosphorylation and activation, thus promoting vascular calcification. 24526702 5 32 theme Thiamet-G 855:863 arg1 administration 837:850 administration 837:850 administration of Thiamet-G, a potent inhibitor for O-GlcNAcase that removes O-GlcNAcylation, 837:929 Elevation of O-GlcNAcylation by administration of Thiamet-G, a potent inhibitor for O-GlcNAcase that removes O-GlcNAcylation, further accelerated vascular calcification and worsened aortic compliance of diabetic mice in vivo. 24526702 11 33 theme molecular 2088:2096 arg1 mechanism 2098:2106 a key molecular mechanism 2082:2106 a key molecular mechanism underlying O-GlcNAcylation-mediated activation of AKT 2082:2160 Our studies have identified a novel causative effect of O-GlcNAcylation in regulating vascular calcification in diabetes mellitus and uncovered a key molecular mechanism underlying O-GlcNAcylation-mediated activation of AKT. 24526702 11 34 theme AKT 2158:2160 arg1 activation 2144:2153 O-GlcNAcylation-mediated activation 2119:2153 O-GlcNAcylation-mediated activation of AKT 2119:2160 Our studies have identified a novel causative effect of O-GlcNAcylation in regulating vascular calcification in diabetes mellitus and uncovered a key molecular mechanism underlying O-GlcNAcylation-mediated activation of AKT. 24526702 0 35 theme AKT 14:16 arg1 Activation 0:9 Activation 0:9 Activation of AKT by O-linked N-acetylglucosamine 0:48 Activation of AKT by O-linked N-acetylglucosamine induces vascular calcification in diabetes mellitus. 24526702 1 36 with patients 239:246 arg1 mellitus 262:269 diabetes mellitus 253:269 diabetes mellitus 253:269 RATIONALE: Vascular calcification is a serious cardiovascular complication that contributes to the increased morbidity and mortality of patients with diabetes mellitus. 24526702 1 37 theme Vascular 114:121 arg1 calcification 123:135 Vascular calcification 114:135 RATIONALE: Vascular calcification 103:135 RATIONALE: Vascular calcification is a serious cardiovascular complication that contributes to the increased morbidity and mortality of patients with diabetes mellitus. 24526702 1 38 theme cardiovascular 150:163 arg1 complication 165:176 a serious cardiovascular complication 140:176 a serious cardiovascular complication that contributes to the increased morbidity and mortality of patients with diabetes mellitus 140:269 RATIONALE: Vascular calcification is a serious cardiovascular complication that contributes to the increased morbidity and mortality of patients with diabetes mellitus. 24526702 1 38 theme cardiovascular 150:163 arg1 RATIONALE 103:111 RATIONALE 103:111 RATIONALE: Vascular calcification 103:135 RATIONALE: Vascular calcification is a serious cardiovascular complication that contributes to the increased morbidity and mortality of patients with diabetes mellitus. 24526702 4 39 theme Low-dose 621:628 arg1 mice 662:665 Low-dose streptozotocin-induced diabetic mice 621:665 Low-dose streptozotocin-induced diabetic mice 621:665 METHODS AND RESULTS: Low-dose streptozotocin-induced diabetic mice exhibited increased aortic O-GlcNAcylation and vascular calcification, which was also associated with impaired aortic compliance in mice. 24526702 2 40 link O-linked 414:421 arg1 O-GlcNAcylation 444:458 O-GlcNAcylation 444:458 O-GlcNAcylation 444:458 Hyperglycemia, a hallmark of diabetes mellitus, is associated with increased vascular calcification and increased modification of proteins by O-linked N-acetylglucosamine (O-GlcNAcylation). 24526702 2 40 link O-linked 414:421 arg1 N-acetylglucosamine 423:441 O-linked N-acetylglucosamine 414:441 O-linked N-acetylglucosamine (O-GlcNAcylation) 414:459 Hyperglycemia, a hallmark of diabetes mellitus, is associated with increased vascular calcification and increased modification of proteins by O-linked N-acetylglucosamine (O-GlcNAcylation). 24526702 7 41 theme transcription 1322:1334 arg1 factor 1336:1341 the osteogenic transcription factor 1307:1341 the osteogenic transcription factor Runx2 1307:1347 Increased O-GlcNAcylation in diabetic arteries or in the O-GlcNAcase knockdown vascular smooth muscle cell upregulated expression of the osteogenic transcription factor Runx2 and enhanced activation of AKT. 24526702 0 42 theme O-linked 21:28 arg1 N-acetylglucosamine 30:48 O-linked N-acetylglucosamine 21:48 O-linked N-acetylglucosamine 21:48 Activation of AKT by O-linked N-acetylglucosamine induces vascular calcification in diabetes mellitus. 24526702 9 43 theme vascular 1760:1767 arg1 muscle 1776:1781 vascular smooth muscle 1760:1781 vascular smooth muscle 1760:1781 Site-directed mutation of AKT at T430 and T479 decreased O-GlcNAcylation, inhibited phosphorylation of AKT at S473 and binding of mammalian target of rapamycin complex 2 to AKT, and subsequently blocked Runx2 transactivity and vascular smooth muscle cell calcification. 24526702 9 44 from S473 1643:1646 arg1 phosphorylation 1617:1631 phosphorylation 1617:1631 phosphorylation of AKT at S473 1617:1646 Site-directed mutation of AKT at T430 and T479 decreased O-GlcNAcylation, inhibited phosphorylation of AKT at S473 and binding of mammalian target of rapamycin complex 2 to AKT, and subsequently blocked Runx2 transactivity and vascular smooth muscle cell calcification. 24526702 9 44 from S473 1643:1646 arg1 binding 1652:1658 binding 1652:1658 binding of mammalian target of rapamycin complex 2 to AKT 1652:1708 Site-directed mutation of AKT at T430 and T479 decreased O-GlcNAcylation, inhibited phosphorylation of AKT at S473 and binding of mammalian target of rapamycin complex 2 to AKT, and subsequently blocked Runx2 transactivity and vascular smooth muscle cell calcification. 24526702 2 45 theme increased 376:384 arg1 modification 386:397 increased modification 376:397 increased modification of proteins by O-linked N-acetylglucosamine (O-GlcNAcylation) 376:459 Hyperglycemia, a hallmark of diabetes mellitus, is associated with increased vascular calcification and increased modification of proteins by O-linked N-acetylglucosamine (O-GlcNAcylation). 24526702 9 46 from T479 1575:1578 arg1 mutation 1547:1554 Site-directed mutation 1533:1554 Site-directed mutation of AKT at T430 and T479 1533:1578 Site-directed mutation of AKT at T430 and T479 decreased O-GlcNAcylation, inhibited phosphorylation of AKT at S473 and binding of mammalian target of rapamycin complex 2 to AKT, and subsequently blocked Runx2 transactivity and vascular smooth muscle cell calcification. 24526702 9 47 theme Site-directed 1533:1545 arg1 mutation 1547:1554 Site-directed mutation 1533:1554 Site-directed mutation of AKT at T430 and T479 1533:1578 Site-directed mutation of AKT at T430 and T479 decreased O-GlcNAcylation, inhibited phosphorylation of AKT at S473 and binding of mammalian target of rapamycin complex 2 to AKT, and subsequently blocked Runx2 transactivity and vascular smooth muscle cell calcification. 24526702 9 48 from T430 1566:1569 arg1 mutation 1547:1554 Site-directed mutation 1533:1554 Site-directed mutation of AKT at T430 and T479 1533:1578 Site-directed mutation of AKT at T430 and T479 decreased O-GlcNAcylation, inhibited phosphorylation of AKT at S473 and binding of mammalian target of rapamycin complex 2 to AKT, and subsequently blocked Runx2 transactivity and vascular smooth muscle cell calcification. 24526702 3 49 theme O-GlcNAcylation 516:530 arg1 role 500:503 the role 496:503 the role of protein O-GlcNAcylation in regulating vascular calcification 496:567 OBJECTIVE: We sought to determine the role of protein O-GlcNAcylation in regulating vascular calcification and the underlying mechanisms. 24526702 3 49 theme O-GlcNAcylation 516:530 arg1 mechanisms 588:597 the underlying mechanisms 573:597 the underlying mechanisms 573:597 OBJECTIVE: We sought to determine the role of protein O-GlcNAcylation in regulating vascular calcification and the underlying mechanisms. 24526702 9 50 dep transactivity 1742:1754 arg1 calcification 1788:1800 cell calcification 1783:1800 cell calcification 1783:1800 Site-directed mutation of AKT at T430 and T479 decreased O-GlcNAcylation, inhibited phosphorylation of AKT at S473 and binding of mammalian target of rapamycin complex 2 to AKT, and subsequently blocked Runx2 transactivity and vascular smooth muscle cell calcification. 24526702 4 51 theme aortic 687:692 arg1 O-GlcNAcylation 694:708 increased aortic O-GlcNAcylation 677:708 increased aortic O-GlcNAcylation 677:708 METHODS AND RESULTS: Low-dose streptozotocin-induced diabetic mice exhibited increased aortic O-GlcNAcylation and vascular calcification, which was also associated with impaired aortic compliance in mice. 24526702 10 52 from sites 1848:1852 arg1 O-GlcNAcylation 1816:1830 O-GlcNAcylation 1816:1830 O-GlcNAcylation of AKT at 2 new sites 1816:1852 CONCLUSIONS: O-GlcNAcylation of AKT at 2 new sites enhanced AKT phosphorylation and activation, thus promoting vascular calcification. 24526702 4 53 theme diabetic 653:660 arg1 mice 662:665 Low-dose streptozotocin-induced diabetic mice 621:665 Low-dose streptozotocin-induced diabetic mice 621:665 METHODS AND RESULTS: Low-dose streptozotocin-induced diabetic mice exhibited increased aortic O-GlcNAcylation and vascular calcification, which was also associated with impaired aortic compliance in mice. 24526702 7 54 theme muscle 1269:1274 arg1 cell 1276:1279 the O-GlcNAcase knockdown vascular smooth muscle cell 1227:1279 the O-GlcNAcase knockdown vascular smooth muscle cell 1227:1279 Increased O-GlcNAcylation in diabetic arteries or in the O-GlcNAcase knockdown vascular smooth muscle cell upregulated expression of the osteogenic transcription factor Runx2 and enhanced activation of AKT. 24526702 11 55 theme diabetes 2050:2057 arg1 mellitus 2059:2066 diabetes mellitus 2050:2066 diabetes mellitus 2050:2066 Our studies have identified a novel causative effect of O-GlcNAcylation in regulating vascular calcification in diabetes mellitus and uncovered a key molecular mechanism underlying O-GlcNAcylation-mediated activation of AKT. 24526702 7 56 theme vascular 1253:1260 arg1 cell 1276:1279 the O-GlcNAcase knockdown vascular smooth muscle cell 1227:1279 the O-GlcNAcase knockdown vascular smooth muscle cell 1227:1279 Increased O-GlcNAcylation in diabetic arteries or in the O-GlcNAcase knockdown vascular smooth muscle cell upregulated expression of the osteogenic transcription factor Runx2 and enhanced activation of AKT. 24526702 2 57 theme diabetes 301:308 arg1 mellitus 310:317 diabetes mellitus 301:317 diabetes mellitus 301:317 Hyperglycemia, a hallmark of diabetes mellitus, is associated with increased vascular calcification and increased modification of proteins by O-linked N-acetylglucosamine (O-GlcNAcylation). 24526702 5 58 theme aortic 987:992 arg1 compliance 994:1003 aortic compliance 987:1003 aortic compliance of diabetic mice 987:1020 Elevation of O-GlcNAcylation by administration of Thiamet-G, a potent inhibitor for O-GlcNAcase that removes O-GlcNAcylation, further accelerated vascular calcification and worsened aortic compliance of diabetic mice in vivo. 24526702 7 59 theme O-GlcNAcase 1231:1241 arg1 cell 1276:1279 the O-GlcNAcase knockdown vascular smooth muscle cell 1227:1279 the O-GlcNAcase knockdown vascular smooth muscle cell 1227:1279 Increased O-GlcNAcylation in diabetic arteries or in the O-GlcNAcase knockdown vascular smooth muscle cell upregulated expression of the osteogenic transcription factor Runx2 and enhanced activation of AKT. 24526702 2 60 theme increased 339:347 arg1 calcification 358:370 increased vascular calcification 339:370 increased vascular calcification 339:370 Hyperglycemia, a hallmark of diabetes mellitus, is associated with increased vascular calcification and increased modification of proteins by O-linked N-acetylglucosamine (O-GlcNAcylation). 24526702 1 61 theme increased 202:210 arg1 morbidity 212:220 morbidity 212:220 morbidity 212:220 RATIONALE: Vascular calcification is a serious cardiovascular complication that contributes to the increased morbidity and mortality of patients with diabetes mellitus. 24526702 5 62 theme vascular 951:958 arg1 calcification 960:972 vascular calcification 951:972 vascular calcification 951:972 Elevation of O-GlcNAcylation by administration of Thiamet-G, a potent inhibitor for O-GlcNAcase that removes O-GlcNAcylation, further accelerated vascular calcification and worsened aortic compliance of diabetic mice in vivo. 24526702 11 63 theme causative 1974:1982 arg1 effect 1984:1989 a novel causative effect 1966:1989 a novel causative effect of O-GlcNAcylation in regulating vascular calcification in diabetes mellitus 1966:2066 Our studies have identified a novel causative effect of O-GlcNAcylation in regulating vascular calcification in diabetes mellitus and uncovered a key molecular mechanism underlying O-GlcNAcylation-mediated activation of AKT. 24526702 6 64 theme O-GlcNAcase 1081:1091 arg1 knockdown 1093:1101 O-GlcNAcase knockdown 1081:1101 O-GlcNAcase knockdown 1081:1101 Increased O-GlcNAcylation, either by Thiamet-G or O-GlcNAcase knockdown, promoted calcification of primary mouse vascular smooth muscle cells. 24526702 11 65 theme vascular 2024:2031 arg1 calcification 2033:2045 vascular calcification 2024:2045 vascular calcification in diabetes mellitus 2024:2066 Our studies have identified a novel causative effect of O-GlcNAcylation in regulating vascular calcification in diabetes mellitus and uncovered a key molecular mechanism underlying O-GlcNAcylation-mediated activation of AKT. 24526702 8 66 from sites 1415:1419 arg1 O-GlcNAcylation 1381:1395 O-GlcNAcylation 1381:1395 O-GlcNAcylation of AKT at two new sites, T430 and T479, 1381:1435 O-GlcNAcylation of AKT at two new sites, T430 and T479, promoted AKT phosphorylation, which in turn enhanced vascular smooth muscle cell calcification. 24526702 8 67 theme AKT 1400:1402 arg1 O-GlcNAcylation 1381:1395 O-GlcNAcylation 1381:1395 O-GlcNAcylation of AKT at two new sites, T430 and T479, 1381:1435 O-GlcNAcylation of AKT at two new sites, T430 and T479, promoted AKT phosphorylation, which in turn enhanced vascular smooth muscle cell calcification. 24526702 7 68 theme Increased 1174:1182 arg1 O-GlcNAcylation 1184:1198 Increased O-GlcNAcylation 1174:1198 Increased O-GlcNAcylation in diabetic arteries or in the O-GlcNAcase knockdown vascular smooth muscle cell 1174:1279 Increased O-GlcNAcylation in diabetic arteries or in the O-GlcNAcase knockdown vascular smooth muscle cell upregulated expression of the osteogenic transcription factor Runx2 and enhanced activation of AKT. 24526702 9 69 theme mammalian 1663:1671 arg1 target 1673:1678 mammalian target 1663:1678 mammalian target of rapamycin complex 2 1663:1701 Site-directed mutation of AKT at T430 and T479 decreased O-GlcNAcylation, inhibited phosphorylation of AKT at S473 and binding of mammalian target of rapamycin complex 2 to AKT, and subsequently blocked Runx2 transactivity and vascular smooth muscle cell calcification. 24526702 10 70 theme AKT 1863:1865 arg1 phosphorylation 1867:1881 AKT phosphorylation 1863:1881 AKT phosphorylation 1863:1881 CONCLUSIONS: O-GlcNAcylation of AKT at 2 new sites enhanced AKT phosphorylation and activation, thus promoting vascular calcification. 24526702 9 71 theme AKT 1636:1638 arg1 phosphorylation 1617:1631 phosphorylation 1617:1631 phosphorylation of AKT at S473 1617:1646 Site-directed mutation of AKT at T430 and T479 decreased O-GlcNAcylation, inhibited phosphorylation of AKT at S473 and binding of mammalian target of rapamycin complex 2 to AKT, and subsequently blocked Runx2 transactivity and vascular smooth muscle cell calcification. 24526702 9 71 theme AKT 1636:1638 arg1 binding 1652:1658 binding 1652:1658 binding of mammalian target of rapamycin complex 2 to AKT 1652:1708 Site-directed mutation of AKT at T430 and T479 decreased O-GlcNAcylation, inhibited phosphorylation of AKT at S473 and binding of mammalian target of rapamycin complex 2 to AKT, and subsequently blocked Runx2 transactivity and vascular smooth muscle cell calcification. 24526702 5 72 theme mice 1017:1020 arg1 compliance 994:1003 aortic compliance 987:1003 aortic compliance of diabetic mice 987:1020 Elevation of O-GlcNAcylation by administration of Thiamet-G, a potent inhibitor for O-GlcNAcase that removes O-GlcNAcylation, further accelerated vascular calcification and worsened aortic compliance of diabetic mice in vivo. 24526702 6 73 theme muscle 1160:1165 arg1 cells 1167:1171 primary mouse vascular smooth muscle cells 1130:1171 primary mouse vascular smooth muscle cells 1130:1171 Increased O-GlcNAcylation, either by Thiamet-G or O-GlcNAcase knockdown, promoted calcification of primary mouse vascular smooth muscle cells. 24526702 4 74 theme aortic 778:783 arg1 compliance 785:794 impaired aortic compliance 769:794 impaired aortic compliance in mice 769:802 METHODS AND RESULTS: Low-dose streptozotocin-induced diabetic mice exhibited increased aortic O-GlcNAcylation and vascular calcification, which was also associated with impaired aortic compliance in mice. 24526702 5 75 theme potent 868:873 arg1 Thiamet-G 855:863 Thiamet-G 855:863 Thiamet-G 855:863 Elevation of O-GlcNAcylation by administration of Thiamet-G, a potent inhibitor for O-GlcNAcase that removes O-GlcNAcylation, further accelerated vascular calcification and worsened aortic compliance of diabetic mice in vivo. 24526702 5 75 theme potent 868:873 arg1 inhibitor 875:883 a potent inhibitor 866:883 a potent inhibitor for O-GlcNAcase that removes O-GlcNAcylation 866:928 Elevation of O-GlcNAcylation by administration of Thiamet-G, a potent inhibitor for O-GlcNAcase that removes O-GlcNAcylation, further accelerated vascular calcification and worsened aortic compliance of diabetic mice in vivo. 24526702 4 76 dep METHODS 600:606 arg1 exhibited 667:675 exhibited 667:675 exhibited increased aortic O-GlcNAcylation and vascular calcification, which was also associated with impaired aortic compliance in mice 667:802 METHODS AND RESULTS: Low-dose streptozotocin-induced diabetic mice exhibited increased aortic O-GlcNAcylation and vascular calcification, which was also associated with impaired aortic compliance in mice. 24526702 9 77 theme complex 1693:1699 arg1 target 1673:1678 mammalian target 1663:1678 mammalian target of rapamycin complex 2 1663:1701 Site-directed mutation of AKT at T430 and T479 decreased O-GlcNAcylation, inhibited phosphorylation of AKT at S473 and binding of mammalian target of rapamycin complex 2 to AKT, and subsequently blocked Runx2 transactivity and vascular smooth muscle cell calcification. 24526702 6 78 theme vascular 1144:1151 arg1 cells 1167:1171 primary mouse vascular smooth muscle cells 1130:1171 primary mouse vascular smooth muscle cells 1130:1171 Increased O-GlcNAcylation, either by Thiamet-G or O-GlcNAcase knockdown, promoted calcification of primary mouse vascular smooth muscle cells. 24526702 1 79 dep RATIONALE 103:111 arg1 calcification 123:135 Vascular calcification 114:135 RATIONALE: Vascular calcification 103:135 RATIONALE: Vascular calcification is a serious cardiovascular complication that contributes to the increased morbidity and mortality of patients with diabetes mellitus. 24526702 7 80 theme AKT 1376:1378 arg1 activation 1362:1371 activation 1362:1371 activation of AKT 1362:1378 Increased O-GlcNAcylation in diabetic arteries or in the O-GlcNAcase knockdown vascular smooth muscle cell upregulated expression of the osteogenic transcription factor Runx2 and enhanced activation of AKT. 24526702 6 81 theme primary 1130:1136 arg1 cells 1167:1171 primary mouse vascular smooth muscle cells 1130:1171 primary mouse vascular smooth muscle cells 1130:1171 Increased O-GlcNAcylation, either by Thiamet-G or O-GlcNAcase knockdown, promoted calcification of primary mouse vascular smooth muscle cells. 24526702 8 82 theme vascular 1490:1497 arg1 calcification 1518:1530 vascular smooth muscle cell calcification 1490:1530 vascular smooth muscle cell calcification 1490:1530 O-GlcNAcylation of AKT at two new sites, T430 and T479, promoted AKT phosphorylation, which in turn enhanced vascular smooth muscle cell calcification. 24526702 11 83 from calcification 2033:2045 arg1 mellitus 2059:2066 diabetes mellitus 2050:2066 diabetes mellitus 2050:2066 Our studies have identified a novel causative effect of O-GlcNAcylation in regulating vascular calcification in diabetes mellitus and uncovered a key molecular mechanism underlying O-GlcNAcylation-mediated activation of AKT. 24526702 8 84 theme muscle 1506:1511 arg1 calcification 1518:1530 vascular smooth muscle cell calcification 1490:1530 vascular smooth muscle cell calcification 1490:1530 O-GlcNAcylation of AKT at two new sites, T430 and T479, promoted AKT phosphorylation, which in turn enhanced vascular smooth muscle cell calcification. 24526702 11 85 theme O-GlcNAcylation-mediated 2119:2142 arg1 activation 2144:2153 O-GlcNAcylation-mediated activation 2119:2153 O-GlcNAcylation-mediated activation of AKT 2119:2160 Our studies have identified a novel causative effect of O-GlcNAcylation in regulating vascular calcification in diabetes mellitus and uncovered a key molecular mechanism underlying O-GlcNAcylation-mediated activation of AKT. 24526702 2 86 theme O-linked 414:421 arg1 O-GlcNAcylation 444:458 O-GlcNAcylation 444:458 O-GlcNAcylation 444:458 Hyperglycemia, a hallmark of diabetes mellitus, is associated with increased vascular calcification and increased modification of proteins by O-linked N-acetylglucosamine (O-GlcNAcylation). 24526702 2 86 theme O-linked 414:421 arg1 N-acetylglucosamine 423:441 O-linked N-acetylglucosamine 414:441 O-linked N-acetylglucosamine (O-GlcNAcylation) 414:459 Hyperglycemia, a hallmark of diabetes mellitus, is associated with increased vascular calcification and increased modification of proteins by O-linked N-acetylglucosamine (O-GlcNAcylation). 24526702 7 87 theme factor 1336:1341 arg1 Runx2 1343:1347 the osteogenic transcription factor Runx2 1307:1347 the osteogenic transcription factor Runx2 1307:1347 Increased O-GlcNAcylation in diabetic arteries or in the O-GlcNAcase knockdown vascular smooth muscle cell upregulated expression of the osteogenic transcription factor Runx2 and enhanced activation of AKT. 24526702 9 88 theme Runx2 1736:1740 arg1 transactivity 1742:1754 Runx2 transactivity 1736:1754 Runx2 transactivity 1736:1754 Site-directed mutation of AKT at T430 and T479 decreased O-GlcNAcylation, inhibited phosphorylation of AKT at S473 and binding of mammalian target of rapamycin complex 2 to AKT, and subsequently blocked Runx2 transactivity and vascular smooth muscle cell calcification. 24526702 4 89 theme streptozotocin-induced 630:651 arg1 mice 662:665 Low-dose streptozotocin-induced diabetic mice 621:665 Low-dose streptozotocin-induced diabetic mice 621:665 METHODS AND RESULTS: Low-dose streptozotocin-induced diabetic mice exhibited increased aortic O-GlcNAcylation and vascular calcification, which was also associated with impaired aortic compliance in mice. 24526702 3 90 theme protein 508:514 arg1 O-GlcNAcylation 516:530 protein O-GlcNAcylation 508:530 protein O-GlcNAcylation 508:530 OBJECTIVE: We sought to determine the role of protein O-GlcNAcylation in regulating vascular calcification and the underlying mechanisms. 24526702 7 91 theme osteogenic 1311:1320 arg1 factor 1336:1341 the osteogenic transcription factor 1307:1341 the osteogenic transcription factor Runx2 1307:1347 Increased O-GlcNAcylation in diabetic arteries or in the O-GlcNAcase knockdown vascular smooth muscle cell upregulated expression of the osteogenic transcription factor Runx2 and enhanced activation of AKT. 24526702 1 92 theme diabetes 253:260 arg1 mellitus 262:269 diabetes mellitus 253:269 diabetes mellitus 253:269 RATIONALE: Vascular calcification is a serious cardiovascular complication that contributes to the increased morbidity and mortality of patients with diabetes mellitus. 24526702 0 93 theme vascular 58:65 arg1 calcification 67:79 vascular calcification 58:79 vascular calcification 58:79 Activation of AKT by O-linked N-acetylglucosamine induces vascular calcification in diabetes mellitus. 24526702 9 94 theme smooth 1769:1774 arg1 muscle 1776:1781 vascular smooth muscle 1760:1781 vascular smooth muscle 1760:1781 Site-directed mutation of AKT at T430 and T479 decreased O-GlcNAcylation, inhibited phosphorylation of AKT at S473 and binding of mammalian target of rapamycin complex 2 to AKT, and subsequently blocked Runx2 transactivity and vascular smooth muscle cell calcification. 24526702 2 95 theme proteins 402:409 arg1 calcification 358:370 increased vascular calcification 339:370 increased vascular calcification 339:370 Hyperglycemia, a hallmark of diabetes mellitus, is associated with increased vascular calcification and increased modification of proteins by O-linked N-acetylglucosamine (O-GlcNAcylation). 24526702 2 95 theme proteins 402:409 arg1 modification 386:397 increased modification 376:397 increased modification of proteins by O-linked N-acetylglucosamine (O-GlcNAcylation) 376:459 Hyperglycemia, a hallmark of diabetes mellitus, is associated with increased vascular calcification and increased modification of proteins by O-linked N-acetylglucosamine (O-GlcNAcylation). 24526702 3 96 theme vascular 546:553 arg1 calcification 555:567 vascular calcification 546:567 vascular calcification 546:567 OBJECTIVE: We sought to determine the role of protein O-GlcNAcylation in regulating vascular calcification and the underlying mechanisms. 24526702 9 97 theme cell 1783:1786 arg1 calcification 1788:1800 cell calcification 1783:1800 cell calcification 1783:1800 Site-directed mutation of AKT at T430 and T479 decreased O-GlcNAcylation, inhibited phosphorylation of AKT at S473 and binding of mammalian target of rapamycin complex 2 to AKT, and subsequently blocked Runx2 transactivity and vascular smooth muscle cell calcification. 24526702 2 98 theme vascular 349:356 arg1 calcification 358:370 increased vascular calcification 339:370 increased vascular calcification 339:370 Hyperglycemia, a hallmark of diabetes mellitus, is associated with increased vascular calcification and increased modification of proteins by O-linked N-acetylglucosamine (O-GlcNAcylation). 24526702 9 99 theme AKT 1559:1561 arg1 mutation 1547:1554 Site-directed mutation 1533:1554 Site-directed mutation of AKT at T430 and T479 1533:1578 Site-directed mutation of AKT at T430 and T479 decreased O-GlcNAcylation, inhibited phosphorylation of AKT at S473 and binding of mammalian target of rapamycin complex 2 to AKT, and subsequently blocked Runx2 transactivity and vascular smooth muscle cell calcification. 24526702 4 100 theme vascular 714:721 arg1 calcification 723:735 vascular calcification 714:735 vascular calcification 714:735 METHODS AND RESULTS: Low-dose streptozotocin-induced diabetic mice exhibited increased aortic O-GlcNAcylation and vascular calcification, which was also associated with impaired aortic compliance in mice. 24526702 3 101 theme underlying 577:586 arg1 mechanisms 588:597 the underlying mechanisms 573:597 the underlying mechanisms 573:597 OBJECTIVE: We sought to determine the role of protein O-GlcNAcylation in regulating vascular calcification and the underlying mechanisms. 28695533 2 0 theme product 566:572 arg1 ions 574:577 unbiased glycan and peptide product ions 538:577 ions 574:577 Traditional mass spectrometry (MS)-based large-scale glycoprotein sequencing studies heavily rely on identifying enzymatically released glycans and their original peptide backbone separately, as there is no efficient fragmentation method to produce unbiased glycan and peptide product ions simultaneously in a single spectrum, and that can be conveniently applied to high throughput glycoproteome characterization, especially for N-glycopeptides, which can have much more branched glycan side chains than relatively less complex O-linked glycans. 28695533 5 1 theme Subsequent 1259:1268 arg1 experiments 1270:1280 Subsequent experiments 1259:1280 Subsequent experiments 1259:1280 Subsequent experiments tested its utility for human plasma N-glycoproteins. 28695533 4 2 theme glycosylation 1227:1239 arg1 sites 1241:1245 five glycosylation sites 1222:1245 five glycosylation sites identified 1222:1256 Fetuin was first utilized to prove the applicability with 19 glycopeptides and corresponding five glycosylation sites identified. 28695533 2 3 theme less 805:808 arg1 glycans 827:833 relatively less complex O-linked glycans 794:833 relatively less complex O-linked glycans 794:833 Traditional mass spectrometry (MS)-based large-scale glycoprotein sequencing studies heavily rely on identifying enzymatically released glycans and their original peptide backbone separately, as there is no efficient fragmentation method to produce unbiased glycan and peptide product ions simultaneously in a single spectrum, and that can be conveniently applied to high throughput glycoproteome characterization, especially for N-glycopeptides, which can have much more branched glycan side chains than relatively less complex O-linked glycans. 28695533 7 4 theme N-glycoproteomics 1608:1624 arg1 analysis 1569:1576 the analysis 1565:1576 the analysis of intact N-glycopeptides and N-glycoproteomics 1565:1624 The integrated fragmentation scheme provides a powerful tool for the analysis of intact N-glycopeptides and N-glycoproteomics. 28695533 2 5 theme peptide 558:564 arg1 ions 574:577 unbiased glycan and peptide product ions 538:577 ions 574:577 Traditional mass spectrometry (MS)-based large-scale glycoprotein sequencing studies heavily rely on identifying enzymatically released glycans and their original peptide backbone separately, as there is no efficient fragmentation method to produce unbiased glycan and peptide product ions simultaneously in a single spectrum, and that can be conveniently applied to high throughput glycoproteome characterization, especially for N-glycopeptides, which can have much more branched glycan side chains than relatively less complex O-linked glycans. 28695533 2 6 theme glycoproteome 672:684 arg1 characterization 686:701 high throughput glycoproteome characterization 656:701 high throughput glycoproteome characterization 656:701 Traditional mass spectrometry (MS)-based large-scale glycoprotein sequencing studies heavily rely on identifying enzymatically released glycans and their original peptide backbone separately, as there is no efficient fragmentation method to produce unbiased glycan and peptide product ions simultaneously in a single spectrum, and that can be conveniently applied to high throughput glycoproteome characterization, especially for N-glycopeptides, which can have much more branched glycan side chains than relatively less complex O-linked glycans. 28695533 6 7 theme progression 1436:1446 arg1 course 1415:1420 the course 1411:1420 the course of restenosis progression to investigate the potential role of glycosylation 1411:1497 Large-scale studies explored N-glycoproteomics in rat carotid arteries over the course of restenosis progression to investigate the potential role of glycosylation. 28695533 3 8 theme glycan 978:983 arg1 fragments 997:1005 both glycan and peptide fragments 973:1005 fragments 997:1005 In this study, a redefined electron-transfer/higher-energy collision dissociation (EThcD) fragmentation scheme is applied to incorporate both glycan and peptide fragments in one single spectrum, enabling complete information to be gathered and great microheterogeneity details to be revealed. 28695533 7 9 theme powerful 1547:1554 arg1 tool 1556:1559 a powerful tool 1545:1559 a powerful tool for the analysis of intact N-glycopeptides and N-glycoproteomics 1545:1624 The integrated fragmentation scheme provides a powerful tool for the analysis of intact N-glycopeptides and N-glycoproteomics. 28695533 2 10 theme throughput 661:670 arg1 characterization 686:701 high throughput glycoproteome characterization 656:701 high throughput glycoproteome characterization 656:701 Traditional mass spectrometry (MS)-based large-scale glycoprotein sequencing studies heavily rely on identifying enzymatically released glycans and their original peptide backbone separately, as there is no efficient fragmentation method to produce unbiased glycan and peptide product ions simultaneously in a single spectrum, and that can be conveniently applied to high throughput glycoproteome characterization, especially for N-glycopeptides, which can have much more branched glycan side chains than relatively less complex O-linked glycans. 28695533 2 11 theme glycoprotein 342:353 arg1 studies 366:372 Traditional mass spectrometry (MS)-based large-scale glycoprotein sequencing studies 289:372 Traditional mass spectrometry (MS)-based large-scale glycoprotein sequencing studies 289:372 Traditional mass spectrometry (MS)-based large-scale glycoprotein sequencing studies heavily rely on identifying enzymatically released glycans and their original peptide backbone separately, as there is no efficient fragmentation method to produce unbiased glycan and peptide product ions simultaneously in a single spectrum, and that can be conveniently applied to high throughput glycoproteome characterization, especially for N-glycopeptides, which can have much more branched glycan side chains than relatively less complex O-linked glycans. 28695533 3 12 theme microheterogeneity 1086:1103 arg1 details 1105:1111 great microheterogeneity details 1080:1111 great microheterogeneity details 1080:1111 In this study, a redefined electron-transfer/higher-energy collision dissociation (EThcD) fragmentation scheme is applied to incorporate both glycan and peptide fragments in one single spectrum, enabling complete information to be gathered and great microheterogeneity details to be revealed. 28695533 2 13 gly glycoprotein 342:353 arg1 glycoprotein 342:353 Traditional mass spectrometry (MS)-based large-scale glycoprotein sequencing studies 289:372 Traditional mass spectrometry (MS)-based large-scale glycoprotein sequencing studies 289:372 Traditional mass spectrometry (MS)-based large-scale glycoprotein sequencing studies heavily rely on identifying enzymatically released glycans and their original peptide backbone separately, as there is no efficient fragmentation method to produce unbiased glycan and peptide product ions simultaneously in a single spectrum, and that can be conveniently applied to high throughput glycoproteome characterization, especially for N-glycopeptides, which can have much more branched glycan side chains than relatively less complex O-linked glycans. 28695533 2 14 theme high 656:659 arg1 characterization 686:701 high throughput glycoproteome characterization 656:701 high throughput glycoproteome characterization 656:701 Traditional mass spectrometry (MS)-based large-scale glycoprotein sequencing studies heavily rely on identifying enzymatically released glycans and their original peptide backbone separately, as there is no efficient fragmentation method to produce unbiased glycan and peptide product ions simultaneously in a single spectrum, and that can be conveniently applied to high throughput glycoproteome characterization, especially for N-glycopeptides, which can have much more branched glycan side chains than relatively less complex O-linked glycans. 28695533 2 15 theme large-scale 330:340 arg1 studies 366:372 Traditional mass spectrometry (MS)-based large-scale glycoprotein sequencing studies 289:372 Traditional mass spectrometry (MS)-based large-scale glycoprotein sequencing studies 289:372 Traditional mass spectrometry (MS)-based large-scale glycoprotein sequencing studies heavily rely on identifying enzymatically released glycans and their original peptide backbone separately, as there is no efficient fragmentation method to produce unbiased glycan and peptide product ions simultaneously in a single spectrum, and that can be conveniently applied to high throughput glycoproteome characterization, especially for N-glycopeptides, which can have much more branched glycan side chains than relatively less complex O-linked glycans. 28695533 3 16 theme single 1014:1019 arg1 spectrum 1021:1028 one single spectrum 1010:1028 one single spectrum 1010:1028 In this study, a redefined electron-transfer/higher-energy collision dissociation (EThcD) fragmentation scheme is applied to incorporate both glycan and peptide fragments in one single spectrum, enabling complete information to be gathered and great microheterogeneity details to be revealed. 28695533 3 17 theme fragmentation 926:938 arg1 scheme 940:945 a redefined electron-transfer/higher-energy collision dissociation (EThcD) fragmentation scheme 851:945 a redefined electron-transfer/higher-energy collision dissociation (EThcD) fragmentation scheme 851:945 In this study, a redefined electron-transfer/higher-energy collision dissociation (EThcD) fragmentation scheme is applied to incorporate both glycan and peptide fragments in one single spectrum, enabling complete information to be gathered and great microheterogeneity details to be revealed. 28695533 4 18 gly glycosylation 1227:1239 arg2 five 1222:1225 five 1222:1225 five 1222:1225 Fetuin was first utilized to prove the applicability with 19 glycopeptides and corresponding five glycosylation sites identified. 28695533 4 18 gly glycosylation 1227:1239 arg2 sites 1241:1245 five glycosylation sites 1222:1245 five glycosylation sites identified 1222:1256 Fetuin was first utilized to prove the applicability with 19 glycopeptides and corresponding five glycosylation sites identified. 28695533 6 19 theme restenosis 1425:1434 arg1 progression 1436:1446 restenosis progression 1425:1446 restenosis progression 1425:1446 Large-scale studies explored N-glycoproteomics in rat carotid arteries over the course of restenosis progression to investigate the potential role of glycosylation. 28695533 2 20 theme O-linked 818:825 arg1 glycans 827:833 relatively less complex O-linked glycans 794:833 relatively less complex O-linked glycans 794:833 Traditional mass spectrometry (MS)-based large-scale glycoprotein sequencing studies heavily rely on identifying enzymatically released glycans and their original peptide backbone separately, as there is no efficient fragmentation method to produce unbiased glycan and peptide product ions simultaneously in a single spectrum, and that can be conveniently applied to high throughput glycoproteome characterization, especially for N-glycopeptides, which can have much more branched glycan side chains than relatively less complex O-linked glycans. 28695533 2 21 theme -based 323:328 arg1 studies 366:372 Traditional mass spectrometry (MS)-based large-scale glycoprotein sequencing studies 289:372 Traditional mass spectrometry (MS)-based large-scale glycoprotein sequencing studies 289:372 Traditional mass spectrometry (MS)-based large-scale glycoprotein sequencing studies heavily rely on identifying enzymatically released glycans and their original peptide backbone separately, as there is no efficient fragmentation method to produce unbiased glycan and peptide product ions simultaneously in a single spectrum, and that can be conveniently applied to high throughput glycoproteome characterization, especially for N-glycopeptides, which can have much more branched glycan side chains than relatively less complex O-linked glycans. 28695533 7 22 theme integrated 1504:1513 arg1 scheme 1529:1534 The integrated fragmentation scheme 1500:1534 The integrated fragmentation scheme 1500:1534 The integrated fragmentation scheme provides a powerful tool for the analysis of intact N-glycopeptides and N-glycoproteomics. 28695533 2 23 link O-linked 818:825 arg1 glycans 827:833 relatively less complex O-linked glycans 794:833 relatively less complex O-linked glycans 794:833 Traditional mass spectrometry (MS)-based large-scale glycoprotein sequencing studies heavily rely on identifying enzymatically released glycans and their original peptide backbone separately, as there is no efficient fragmentation method to produce unbiased glycan and peptide product ions simultaneously in a single spectrum, and that can be conveniently applied to high throughput glycoproteome characterization, especially for N-glycopeptides, which can have much more branched glycan side chains than relatively less complex O-linked glycans. 28695533 4 24 with applicability 1168:1180 arg1 glycopeptides 1190:1202 19 glycopeptides 1187:1202 19 glycopeptides 1187:1202 Fetuin was first utilized to prove the applicability with 19 glycopeptides and corresponding five glycosylation sites identified. 28695533 2 25 theme glycan 770:775 arg1 chains 782:787 much more branched glycan side chains 751:787 much more branched glycan side chains 751:787 Traditional mass spectrometry (MS)-based large-scale glycoprotein sequencing studies heavily rely on identifying enzymatically released glycans and their original peptide backbone separately, as there is no efficient fragmentation method to produce unbiased glycan and peptide product ions simultaneously in a single spectrum, and that can be conveniently applied to high throughput glycoproteome characterization, especially for N-glycopeptides, which can have much more branched glycan side chains than relatively less complex O-linked glycans. 28695533 1 26 theme Protein 123:129 arg1 one 146:148 one 146:148 one 146:148 Protein glycosylation, one of the most heterogeneous post-translational modifications, can play a major role in cellular signal transduction and disease progression. 28695533 1 26 theme Protein 123:129 arg1 modifications 195:207 the most heterogeneous post-translational modifications 153:207 the most heterogeneous post-translational modifications 153:207 Protein glycosylation, one of the most heterogeneous post-translational modifications, can play a major role in cellular signal transduction and disease progression. 28695533 1 26 theme Protein 123:129 arg1 glycosylation 131:143 Protein glycosylation 123:143 Protein glycosylation 123:143 Protein glycosylation, one of the most heterogeneous post-translational modifications, can play a major role in cellular signal transduction and disease progression. 28695533 1 27 theme major 221:225 arg1 role 227:230 a major role 219:230 a major role 219:230 Protein glycosylation, one of the most heterogeneous post-translational modifications, can play a major role in cellular signal transduction and disease progression. 28695533 0 28 theme Collision 32:40 arg1 Dissociation 42:53 Electron-Transfer/Higher-Energy Collision Dissociation 0:53 Electron-Transfer/Higher-Energy Collision Dissociation (EThcD) 0:61 Electron-Transfer/Higher-Energy Collision Dissociation (EThcD)-Enabled Intact Glycopeptide/Glycoproteome Characterization. 28695533 0 28 theme Collision 32:40 arg1 EThcD 56:60 EThcD 56:60 EThcD 56:60 Electron-Transfer/Higher-Energy Collision Dissociation (EThcD)-Enabled Intact Glycopeptide/Glycoproteome Characterization. 28695533 2 29 theme branched 761:768 arg1 chains 782:787 much more branched glycan side chains 751:787 much more branched glycan side chains 751:787 Traditional mass spectrometry (MS)-based large-scale glycoprotein sequencing studies heavily rely on identifying enzymatically released glycans and their original peptide backbone separately, as there is no efficient fragmentation method to produce unbiased glycan and peptide product ions simultaneously in a single spectrum, and that can be conveniently applied to high throughput glycoproteome characterization, especially for N-glycopeptides, which can have much more branched glycan side chains than relatively less complex O-linked glycans. 28695533 7 30 theme N-glycopeptides 1588:1602 arg1 analysis 1569:1576 the analysis 1565:1576 the analysis of intact N-glycopeptides and N-glycoproteomics 1565:1624 The integrated fragmentation scheme provides a powerful tool for the analysis of intact N-glycopeptides and N-glycoproteomics. 28695533 0 31 theme Electron-Transfer/Higher-Energy 0:30 arg1 Dissociation 42:53 Electron-Transfer/Higher-Energy Collision Dissociation 0:53 Electron-Transfer/Higher-Energy Collision Dissociation (EThcD) 0:61 Electron-Transfer/Higher-Energy Collision Dissociation (EThcD)-Enabled Intact Glycopeptide/Glycoproteome Characterization. 28695533 0 31 theme Electron-Transfer/Higher-Energy 0:30 arg1 EThcD 56:60 EThcD 56:60 EThcD 56:60 Electron-Transfer/Higher-Energy Collision Dissociation (EThcD)-Enabled Intact Glycopeptide/Glycoproteome Characterization. 28695533 5 32 theme plasma 1311:1316 arg1 N-glycoproteins 1318:1332 human plasma N-glycoproteins 1305:1332 human plasma N-glycoproteins 1305:1332 Subsequent experiments tested its utility for human plasma N-glycoproteins. 28695533 9 33 theme Graphical 1732:1740 arg1 Abstract 1742:1749 Graphical Abstract 1732:1749 Graphical Abstract 1732:1749 Graphical Abstract ᅟ. 28695533 3 34 theme complete 1040:1047 arg1 information 1049:1059 complete information 1040:1059 complete information 1040:1059 In this study, a redefined electron-transfer/higher-energy collision dissociation (EThcD) fragmentation scheme is applied to incorporate both glycan and peptide fragments in one single spectrum, enabling complete information to be gathered and great microheterogeneity details to be revealed. 28695533 2 35 theme peptide 452:458 arg1 backbone 460:467 their original peptide backbone 437:467 their original peptide backbone separately 437:478 Traditional mass spectrometry (MS)-based large-scale glycoprotein sequencing studies heavily rely on identifying enzymatically released glycans and their original peptide backbone separately, as there is no efficient fragmentation method to produce unbiased glycan and peptide product ions simultaneously in a single spectrum, and that can be conveniently applied to high throughput glycoproteome characterization, especially for N-glycopeptides, which can have much more branched glycan side chains than relatively less complex O-linked glycans. 28695533 2 36 theme fragmentation 506:518 arg1 method 520:525 no efficient fragmentation method 493:525 no efficient fragmentation method to produce unbiased glycan and peptide product ions simultaneously in a single spectrum 493:613 Traditional mass spectrometry (MS)-based large-scale glycoprotein sequencing studies heavily rely on identifying enzymatically released glycans and their original peptide backbone separately, as there is no efficient fragmentation method to produce unbiased glycan and peptide product ions simultaneously in a single spectrum, and that can be conveniently applied to high throughput glycoproteome characterization, especially for N-glycopeptides, which can have much more branched glycan side chains than relatively less complex O-linked glycans. 28695533 1 37 theme cellular 235:242 arg1 transduction 251:262 cellular signal transduction 235:262 cellular signal transduction 235:262 Protein glycosylation, one of the most heterogeneous post-translational modifications, can play a major role in cellular signal transduction and disease progression. 28695533 2 38 contain have 746:749 arg2 chains 782:787 much more branched glycan side chains 751:787 much more branched glycan side chains 751:787 Traditional mass spectrometry (MS)-based large-scale glycoprotein sequencing studies heavily rely on identifying enzymatically released glycans and their original peptide backbone separately, as there is no efficient fragmentation method to produce unbiased glycan and peptide product ions simultaneously in a single spectrum, and that can be conveniently applied to high throughput glycoproteome characterization, especially for N-glycopeptides, which can have much more branched glycan side chains than relatively less complex O-linked glycans. 28695533 2 38 contain have 746:749 arg1 N-glycopeptides 719:733 N-glycopeptides 719:733 N-glycopeptides 719:733 Traditional mass spectrometry (MS)-based large-scale glycoprotein sequencing studies heavily rely on identifying enzymatically released glycans and their original peptide backbone separately, as there is no efficient fragmentation method to produce unbiased glycan and peptide product ions simultaneously in a single spectrum, and that can be conveniently applied to high throughput glycoproteome characterization, especially for N-glycopeptides, which can have much more branched glycan side chains than relatively less complex O-linked glycans. 28695533 2 39 theme original 443:450 arg1 backbone 460:467 their original peptide backbone 437:467 their original peptide backbone separately 437:478 Traditional mass spectrometry (MS)-based large-scale glycoprotein sequencing studies heavily rely on identifying enzymatically released glycans and their original peptide backbone separately, as there is no efficient fragmentation method to produce unbiased glycan and peptide product ions simultaneously in a single spectrum, and that can be conveniently applied to high throughput glycoproteome characterization, especially for N-glycopeptides, which can have much more branched glycan side chains than relatively less complex O-linked glycans. 28695533 2 40 theme sequencing 355:364 arg1 studies 366:372 Traditional mass spectrometry (MS)-based large-scale glycoprotein sequencing studies 289:372 Traditional mass spectrometry (MS)-based large-scale glycoprotein sequencing studies 289:372 Traditional mass spectrometry (MS)-based large-scale glycoprotein sequencing studies heavily rely on identifying enzymatically released glycans and their original peptide backbone separately, as there is no efficient fragmentation method to produce unbiased glycan and peptide product ions simultaneously in a single spectrum, and that can be conveniently applied to high throughput glycoproteome characterization, especially for N-glycopeptides, which can have much more branched glycan side chains than relatively less complex O-linked glycans. 28695533 2 41 theme unbiased 538:545 arg1 glycan 547:552 unbiased glycan and peptide product ions 538:577 glycan 547:552 Traditional mass spectrometry (MS)-based large-scale glycoprotein sequencing studies heavily rely on identifying enzymatically released glycans and their original peptide backbone separately, as there is no efficient fragmentation method to produce unbiased glycan and peptide product ions simultaneously in a single spectrum, and that can be conveniently applied to high throughput glycoproteome characterization, especially for N-glycopeptides, which can have much more branched glycan side chains than relatively less complex O-linked glycans. 28695533 1 42 theme signal 244:249 arg1 transduction 251:262 cellular signal transduction 235:262 cellular signal transduction 235:262 Protein glycosylation, one of the most heterogeneous post-translational modifications, can play a major role in cellular signal transduction and disease progression. 28695533 4 43 gly glycopeptides 1190:1202 arg2 glycopeptides 1190:1202 19 glycopeptides 1187:1202 19 glycopeptides 1187:1202 Fetuin was first utilized to prove the applicability with 19 glycopeptides and corresponding five glycosylation sites identified. 28695533 2 44 theme Traditional 289:299 arg1 spectrometry 306:317 Traditional mass spectrometry 289:317 Traditional mass spectrometry (MS) 289:322 Traditional mass spectrometry (MS)-based large-scale glycoprotein sequencing studies heavily rely on identifying enzymatically released glycans and their original peptide backbone separately, as there is no efficient fragmentation method to produce unbiased glycan and peptide product ions simultaneously in a single spectrum, and that can be conveniently applied to high throughput glycoproteome characterization, especially for N-glycopeptides, which can have much more branched glycan side chains than relatively less complex O-linked glycans. 28695533 2 44 theme Traditional 289:299 arg1 MS 320:321 MS 320:321 MS 320:321 Traditional mass spectrometry (MS)-based large-scale glycoprotein sequencing studies heavily rely on identifying enzymatically released glycans and their original peptide backbone separately, as there is no efficient fragmentation method to produce unbiased glycan and peptide product ions simultaneously in a single spectrum, and that can be conveniently applied to high throughput glycoproteome characterization, especially for N-glycopeptides, which can have much more branched glycan side chains than relatively less complex O-linked glycans. 28695533 3 45 theme redefined 853:861 arg1 scheme 940:945 a redefined electron-transfer/higher-energy collision dissociation (EThcD) fragmentation scheme 851:945 a redefined electron-transfer/higher-energy collision dissociation (EThcD) fragmentation scheme 851:945 In this study, a redefined electron-transfer/higher-energy collision dissociation (EThcD) fragmentation scheme is applied to incorporate both glycan and peptide fragments in one single spectrum, enabling complete information to be gathered and great microheterogeneity details to be revealed. 28695533 5 46 gly N-glycoproteins 1318:1332 arg1 N-glycoproteins 1318:1332 human plasma N-glycoproteins 1305:1332 human plasma N-glycoproteins 1305:1332 Subsequent experiments tested its utility for human plasma N-glycoproteins. 28695533 3 47 theme dissociation 905:916 arg1 scheme 940:945 a redefined electron-transfer/higher-energy collision dissociation (EThcD) fragmentation scheme 851:945 a redefined electron-transfer/higher-energy collision dissociation (EThcD) fragmentation scheme 851:945 In this study, a redefined electron-transfer/higher-energy collision dissociation (EThcD) fragmentation scheme is applied to incorporate both glycan and peptide fragments in one single spectrum, enabling complete information to be gathered and great microheterogeneity details to be revealed. 28695533 0 48 theme Intact 71:76 arg1 Characterization 105:120 Intact Glycopeptide/Glycoproteome Characterization 71:120 Intact Glycopeptide/Glycoproteome Characterization 71:120 Electron-Transfer/Higher-Energy Collision Dissociation (EThcD)-Enabled Intact Glycopeptide/Glycoproteome Characterization. 28695533 3 49 theme electron-transfer/higher-energy 863:893 arg1 scheme 940:945 a redefined electron-transfer/higher-energy collision dissociation (EThcD) fragmentation scheme 851:945 a redefined electron-transfer/higher-energy collision dissociation (EThcD) fragmentation scheme 851:945 In this study, a redefined electron-transfer/higher-energy collision dissociation (EThcD) fragmentation scheme is applied to incorporate both glycan and peptide fragments in one single spectrum, enabling complete information to be gathered and great microheterogeneity details to be revealed. 28695533 6 50 theme glycosylation 1485:1497 arg1 role 1477:1480 the potential role 1463:1480 the potential role of glycosylation 1463:1497 Large-scale studies explored N-glycoproteomics in rat carotid arteries over the course of restenosis progression to investigate the potential role of glycosylation. 28695533 7 51 gly N-glycopeptides 1588:1602 arg2 N-glycopeptides 1588:1602 intact N-glycopeptides 1581:1602 intact N-glycopeptides 1581:1602 The integrated fragmentation scheme provides a powerful tool for the analysis of intact N-glycopeptides and N-glycoproteomics. 28695533 6 52 theme carotid 1389:1395 arg1 arteries 1397:1404 rat carotid arteries 1385:1404 rat carotid arteries 1385:1404 Large-scale studies explored N-glycoproteomics in rat carotid arteries over the course of restenosis progression to investigate the potential role of glycosylation. 28695533 2 53 theme released 416:423 arg1 glycans 425:431 enzymatically released glycans 402:431 enzymatically released glycans 402:431 Traditional mass spectrometry (MS)-based large-scale glycoprotein sequencing studies heavily rely on identifying enzymatically released glycans and their original peptide backbone separately, as there is no efficient fragmentation method to produce unbiased glycan and peptide product ions simultaneously in a single spectrum, and that can be conveniently applied to high throughput glycoproteome characterization, especially for N-glycopeptides, which can have much more branched glycan side chains than relatively less complex O-linked glycans. 28695533 8 54 theme O-glycoproteome 1698:1712 arg1 characterization 1714:1729 large-scale O-glycoproteome characterization 1686:1729 large-scale O-glycoproteome characterization 1686:1729 We also anticipate this approach can be readily applied to large-scale O-glycoproteome characterization. 28695533 6 55 theme rat 1385:1387 arg1 arteries 1397:1404 rat carotid arteries 1385:1404 rat carotid arteries 1385:1404 Large-scale studies explored N-glycoproteomics in rat carotid arteries over the course of restenosis progression to investigate the potential role of glycosylation. 28695533 7 56 theme fragmentation 1515:1527 arg1 scheme 1529:1534 The integrated fragmentation scheme 1500:1534 The integrated fragmentation scheme 1500:1534 The integrated fragmentation scheme provides a powerful tool for the analysis of intact N-glycopeptides and N-glycoproteomics. 28695533 1 57 theme most 157:160 arg1 modifications 195:207 the most heterogeneous post-translational modifications 153:207 the most heterogeneous post-translational modifications 153:207 Protein glycosylation, one of the most heterogeneous post-translational modifications, can play a major role in cellular signal transduction and disease progression. 28695533 5 58 theme human 1305:1309 arg1 N-glycoproteins 1318:1332 human plasma N-glycoproteins 1305:1332 human plasma N-glycoproteins 1305:1332 Subsequent experiments tested its utility for human plasma N-glycoproteins. 28695533 2 59 theme side 777:780 arg1 chains 782:787 much more branched glycan side chains 751:787 much more branched glycan side chains 751:787 Traditional mass spectrometry (MS)-based large-scale glycoprotein sequencing studies heavily rely on identifying enzymatically released glycans and their original peptide backbone separately, as there is no efficient fragmentation method to produce unbiased glycan and peptide product ions simultaneously in a single spectrum, and that can be conveniently applied to high throughput glycoproteome characterization, especially for N-glycopeptides, which can have much more branched glycan side chains than relatively less complex O-linked glycans. 28695533 1 60 theme heterogeneous 162:174 arg1 modifications 195:207 the most heterogeneous post-translational modifications 153:207 the most heterogeneous post-translational modifications 153:207 Protein glycosylation, one of the most heterogeneous post-translational modifications, can play a major role in cellular signal transduction and disease progression. 28695533 3 61 theme great 1080:1084 arg1 details 1105:1111 great microheterogeneity details 1080:1111 great microheterogeneity details 1080:1111 In this study, a redefined electron-transfer/higher-energy collision dissociation (EThcD) fragmentation scheme is applied to incorporate both glycan and peptide fragments in one single spectrum, enabling complete information to be gathered and great microheterogeneity details to be revealed. 28695533 1 62 theme disease 268:274 arg1 progression 276:286 disease progression 268:286 disease progression 268:286 Protein glycosylation, one of the most heterogeneous post-translational modifications, can play a major role in cellular signal transduction and disease progression. 28695533 6 63 theme potential 1467:1475 arg1 role 1477:1480 the potential role 1463:1480 the potential role of glycosylation 1463:1497 Large-scale studies explored N-glycoproteomics in rat carotid arteries over the course of restenosis progression to investigate the potential role of glycosylation. 28695533 6 64 theme Large-scale 1335:1345 arg1 studies 1347:1353 Large-scale studies 1335:1353 Large-scale studies 1335:1353 Large-scale studies explored N-glycoproteomics in rat carotid arteries over the course of restenosis progression to investigate the potential role of glycosylation. 28695533 8 65 theme large-scale 1686:1696 arg1 characterization 1714:1729 large-scale O-glycoproteome characterization 1686:1729 large-scale O-glycoproteome characterization 1686:1729 We also anticipate this approach can be readily applied to large-scale O-glycoproteome characterization. 28695533 1 66 theme post-translational 176:193 arg1 modifications 195:207 the most heterogeneous post-translational modifications 153:207 the most heterogeneous post-translational modifications 153:207 Protein glycosylation, one of the most heterogeneous post-translational modifications, can play a major role in cellular signal transduction and disease progression. 28695533 7 67 theme intact 1581:1586 arg1 N-glycopeptides 1588:1602 intact N-glycopeptides 1581:1602 intact N-glycopeptides 1581:1602 The integrated fragmentation scheme provides a powerful tool for the analysis of intact N-glycopeptides and N-glycoproteomics. 28695533 3 68 theme EThcD 919:923 arg1 scheme 940:945 a redefined electron-transfer/higher-energy collision dissociation (EThcD) fragmentation scheme 851:945 a redefined electron-transfer/higher-energy collision dissociation (EThcD) fragmentation scheme 851:945 In this study, a redefined electron-transfer/higher-energy collision dissociation (EThcD) fragmentation scheme is applied to incorporate both glycan and peptide fragments in one single spectrum, enabling complete information to be gathered and great microheterogeneity details to be revealed. 28695533 6 69 from N-glycoproteomics 1364:1380 arg1 arteries 1397:1404 rat carotid arteries 1385:1404 rat carotid arteries 1385:1404 Large-scale studies explored N-glycoproteomics in rat carotid arteries over the course of restenosis progression to investigate the potential role of glycosylation. 28695533 2 70 theme efficient 496:504 arg1 method 520:525 no efficient fragmentation method 493:525 no efficient fragmentation method to produce unbiased glycan and peptide product ions simultaneously in a single spectrum 493:613 Traditional mass spectrometry (MS)-based large-scale glycoprotein sequencing studies heavily rely on identifying enzymatically released glycans and their original peptide backbone separately, as there is no efficient fragmentation method to produce unbiased glycan and peptide product ions simultaneously in a single spectrum, and that can be conveniently applied to high throughput glycoproteome characterization, especially for N-glycopeptides, which can have much more branched glycan side chains than relatively less complex O-linked glycans. 28695533 1 71 theme modifications 195:207 arg1 one 146:148 one 146:148 one 146:148 Protein glycosylation, one of the most heterogeneous post-translational modifications, can play a major role in cellular signal transduction and disease progression. 28695533 1 71 theme modifications 195:207 arg1 glycosylation 131:143 Protein glycosylation 123:143 Protein glycosylation 123:143 Protein glycosylation, one of the most heterogeneous post-translational modifications, can play a major role in cellular signal transduction and disease progression. 28695533 1 71 theme modifications 195:207 arg1 modifications 195:207 the most heterogeneous post-translational modifications 153:207 the most heterogeneous post-translational modifications 153:207 Protein glycosylation, one of the most heterogeneous post-translational modifications, can play a major role in cellular signal transduction and disease progression. 28695533 2 72 gly N-glycopeptides 719:733 arg2 N-glycopeptides 719:733 N-glycopeptides 719:733 N-glycopeptides 719:733 Traditional mass spectrometry (MS)-based large-scale glycoprotein sequencing studies heavily rely on identifying enzymatically released glycans and their original peptide backbone separately, as there is no efficient fragmentation method to produce unbiased glycan and peptide product ions simultaneously in a single spectrum, and that can be conveniently applied to high throughput glycoproteome characterization, especially for N-glycopeptides, which can have much more branched glycan side chains than relatively less complex O-linked glycans. 28695533 3 73 theme collision 895:903 arg1 scheme 940:945 a redefined electron-transfer/higher-energy collision dissociation (EThcD) fragmentation scheme 851:945 a redefined electron-transfer/higher-energy collision dissociation (EThcD) fragmentation scheme 851:945 In this study, a redefined electron-transfer/higher-energy collision dissociation (EThcD) fragmentation scheme is applied to incorporate both glycan and peptide fragments in one single spectrum, enabling complete information to be gathered and great microheterogeneity details to be revealed. 28695533 0 74 theme Glycopeptide/Glycoproteome 78:103 arg1 Characterization 105:120 Intact Glycopeptide/Glycoproteome Characterization 71:120 Intact Glycopeptide/Glycoproteome Characterization 71:120 Electron-Transfer/Higher-Energy Collision Dissociation (EThcD)-Enabled Intact Glycopeptide/Glycoproteome Characterization. 28695533 4 75 used utilized 1146:1153 arg2 Fetuin 1129:1134 Fetuin 1129:1134 Fetuin 1129:1134 Fetuin was first utilized to prove the applicability with 19 glycopeptides and corresponding five glycosylation sites identified. 28695533 2 76 theme mass 301:304 arg1 spectrometry 306:317 Traditional mass spectrometry 289:317 Traditional mass spectrometry (MS) 289:322 Traditional mass spectrometry (MS)-based large-scale glycoprotein sequencing studies heavily rely on identifying enzymatically released glycans and their original peptide backbone separately, as there is no efficient fragmentation method to produce unbiased glycan and peptide product ions simultaneously in a single spectrum, and that can be conveniently applied to high throughput glycoproteome characterization, especially for N-glycopeptides, which can have much more branched glycan side chains than relatively less complex O-linked glycans. 28695533 2 76 theme mass 301:304 arg1 MS 320:321 MS 320:321 MS 320:321 Traditional mass spectrometry (MS)-based large-scale glycoprotein sequencing studies heavily rely on identifying enzymatically released glycans and their original peptide backbone separately, as there is no efficient fragmentation method to produce unbiased glycan and peptide product ions simultaneously in a single spectrum, and that can be conveniently applied to high throughput glycoproteome characterization, especially for N-glycopeptides, which can have much more branched glycan side chains than relatively less complex O-linked glycans. 28695533 2 77 theme complex 810:816 arg1 glycans 827:833 relatively less complex O-linked glycans 794:833 relatively less complex O-linked glycans 794:833 Traditional mass spectrometry (MS)-based large-scale glycoprotein sequencing studies heavily rely on identifying enzymatically released glycans and their original peptide backbone separately, as there is no efficient fragmentation method to produce unbiased glycan and peptide product ions simultaneously in a single spectrum, and that can be conveniently applied to high throughput glycoproteome characterization, especially for N-glycopeptides, which can have much more branched glycan side chains than relatively less complex O-linked glycans. 28695533 3 78 theme peptide 989:995 arg1 fragments 997:1005 both glycan and peptide fragments 973:1005 fragments 997:1005 In this study, a redefined electron-transfer/higher-energy collision dissociation (EThcD) fragmentation scheme is applied to incorporate both glycan and peptide fragments in one single spectrum, enabling complete information to be gathered and great microheterogeneity details to be revealed. 28695533 2 79 theme single 599:604 arg1 spectrum 606:613 a single spectrum 597:613 a single spectrum 597:613 Traditional mass spectrometry (MS)-based large-scale glycoprotein sequencing studies heavily rely on identifying enzymatically released glycans and their original peptide backbone separately, as there is no efficient fragmentation method to produce unbiased glycan and peptide product ions simultaneously in a single spectrum, and that can be conveniently applied to high throughput glycoproteome characterization, especially for N-glycopeptides, which can have much more branched glycan side chains than relatively less complex O-linked glycans. 28419276 0 0 theme Immunodeficiency 76:91 arg1 Type 99:102 Sexually Transmitted Human Immunodeficiency Virus Type 1 49:104 Sexually Transmitted Human Immunodeficiency Virus Type 1 49:104 Molecular Features of the V1-V4 Coding Region of Sexually Transmitted Human Immunodeficiency Virus Type 1. 28419276 1 1 theme pairs 333:337 arg1 number 296:301 the small number 286:301 the small number of characterized transmission pairs in individual studies 286:359 Background.: Investigations into which human immunodeficiency virus type 1 (HIV-1) sequence features may be selected for transmission during sexual exposure have been hampered by the small number of characterized transmission pairs in individual studies. 28419276 2 2 theme transmission 592:603 arg1 pairs 605:609 58 transmission pairs 589:609 58 transmission pairs from previous studies using mixed-effects linear regression 589:669 Methods.: To boost statistical power to detect differences in glycosylation, length, and electrical charge in the HIV-1 V1-V4 coding region, we reanalyzed all available 2485 env sequences derived from 114 subjects representing 58 transmission pairs from previous studies using mixed-effects linear regression and an approach to approximate the unobserved transmitted virus. 28419276 2 3 from differences 409:419 arg1 length 439:444 length 439:444 length 439:444 Methods.: To boost statistical power to detect differences in glycosylation, length, and electrical charge in the HIV-1 V1-V4 coding region, we reanalyzed all available 2485 env sequences derived from 114 subjects representing 58 transmission pairs from previous studies using mixed-effects linear regression and an approach to approximate the unobserved transmitted virus. 28419276 2 3 from differences 409:419 arg1 glycosylation 424:436 glycosylation 424:436 glycosylation 424:436 Methods.: To boost statistical power to detect differences in glycosylation, length, and electrical charge in the HIV-1 V1-V4 coding region, we reanalyzed all available 2485 env sequences derived from 114 subjects representing 58 transmission pairs from previous studies using mixed-effects linear regression and an approach to approximate the unobserved transmitted virus. 28419276 2 3 from differences 409:419 arg1 charge 462:467 electrical charge 451:467 electrical charge 451:467 Methods.: To boost statistical power to detect differences in glycosylation, length, and electrical charge in the HIV-1 V1-V4 coding region, we reanalyzed all available 2485 env sequences derived from 114 subjects representing 58 transmission pairs from previous studies using mixed-effects linear regression and an approach to approximate the unobserved transmitted virus. 28419276 2 3 from differences 409:419 arg1 region 495:500 the HIV-1 V1-V4 coding region 472:500 the HIV-1 V1-V4 coding region 472:500 Methods.: To boost statistical power to detect differences in glycosylation, length, and electrical charge in the HIV-1 V1-V4 coding region, we reanalyzed all available 2485 env sequences derived from 114 subjects representing 58 transmission pairs from previous studies using mixed-effects linear regression and an approach to approximate the unobserved transmitted virus. 28419276 1 4 theme immunodeficiency 152:167 arg1 type 175:178 human immunodeficiency virus type 1 146:180 human immunodeficiency virus type 1 (HIV-1) sequence features 146:206 Background.: Investigations into which human immunodeficiency virus type 1 (HIV-1) sequence features may be selected for transmission during sexual exposure have been hampered by the small number of characterized transmission pairs in individual studies. 28419276 1 4 theme immunodeficiency 152:167 arg1 HIV-1 183:187 HIV-1 183:187 HIV-1 183:187 Background.: Investigations into which human immunodeficiency virus type 1 (HIV-1) sequence features may be selected for transmission during sexual exposure have been hampered by the small number of characterized transmission pairs in individual studies. 28419276 4 5 theme V1-V4 1048:1052 arg1 sequences 1054:1062 V1-V4 sequences 1048:1062 V1-V4 sequences 1048:1062 We also detected a trend toward more PNGS and lower isoelectric points in transmitted sequences with source partner and the evolutionary tendency to shorten V1-V4 sequences, reduce the number of PNGS, and lower isoelectric points in the recipient following transmission. 28419276 5 6 theme available 1189:1197 arg1 sequences 1222:1230 all available well-characterized env sequences 1185:1230 all available well-characterized env sequences from transmission pairs 1185:1254 Conclusions.: By using all available well-characterized env sequences from transmission pairs via sexual exposure, we were able to identify several important virologic factors that may be important in the development of biomedical preventive interventions. 28419276 0 7 theme Human 70:74 arg1 Type 99:102 Sexually Transmitted Human Immunodeficiency Virus Type 1 49:104 Sexually Transmitted Human Immunodeficiency Virus Type 1 49:104 Molecular Features of the V1-V4 Coding Region of Sexually Transmitted Human Immunodeficiency Virus Type 1. 28419276 2 8 theme HIV-1 476:480 arg1 region 495:500 the HIV-1 V1-V4 coding region 472:500 the HIV-1 V1-V4 coding region 472:500 Methods.: To boost statistical power to detect differences in glycosylation, length, and electrical charge in the HIV-1 V1-V4 coding region, we reanalyzed all available 2485 env sequences derived from 114 subjects representing 58 transmission pairs from previous studies using mixed-effects linear regression and an approach to approximate the unobserved transmitted virus. 28419276 1 9 theme virus 169:173 arg1 type 175:178 human immunodeficiency virus type 1 146:180 human immunodeficiency virus type 1 (HIV-1) sequence features 146:206 Background.: Investigations into which human immunodeficiency virus type 1 (HIV-1) sequence features may be selected for transmission during sexual exposure have been hampered by the small number of characterized transmission pairs in individual studies. 28419276 1 9 theme virus 169:173 arg1 HIV-1 183:187 HIV-1 183:187 HIV-1 183:187 Background.: Investigations into which human immunodeficiency virus type 1 (HIV-1) sequence features may be selected for transmission during sexual exposure have been hampered by the small number of characterized transmission pairs in individual studies. 28419276 1 10 theme sexual 248:253 arg1 exposure 255:262 sexual exposure 248:262 sexual exposure 248:262 Background.: Investigations into which human immunodeficiency virus type 1 (HIV-1) sequence features may be selected for transmission during sexual exposure have been hampered by the small number of characterized transmission pairs in individual studies. 28419276 0 11 theme Type 99:102 arg1 Region 39:44 the V1-V4 Coding Region 22:44 the V1-V4 Coding Region of Sexually Transmitted Human Immunodeficiency Virus Type 1 22:104 Molecular Features of the V1-V4 Coding Region of Sexually Transmitted Human Immunodeficiency Virus Type 1. 28419276 1 12 theme individual 342:351 arg1 studies 353:359 individual studies 342:359 individual studies 342:359 Background.: Investigations into which human immunodeficiency virus type 1 (HIV-1) sequence features may be selected for transmission during sexual exposure have been hampered by the small number of characterized transmission pairs in individual studies. 28419276 2 13 theme linear 653:658 arg1 regression 660:669 mixed-effects linear regression 639:669 mixed-effects linear regression 639:669 Methods.: To boost statistical power to detect differences in glycosylation, length, and electrical charge in the HIV-1 V1-V4 coding region, we reanalyzed all available 2485 env sequences derived from 114 subjects representing 58 transmission pairs from previous studies using mixed-effects linear regression and an approach to approximate the unobserved transmitted virus. 28419276 3 14 theme source 875:880 arg1 partner 882:888 the source partner 871:888 the source partner 871:888 Results.: The recipient partner had a shorter V1-V4 region and fewer potential N-linked glycosylation sites (PNGS) than sequences from the source partner. 28419276 3 15 theme glycosylation 824:836 arg1 sites 838:842 potential N-linked glycosylation sites 805:842 fewer potential N-linked glycosylation sites (PNGS) 799:849 Results.: The recipient partner had a shorter V1-V4 region and fewer potential N-linked glycosylation sites (PNGS) than sequences from the source partner. 28419276 3 15 theme glycosylation 824:836 arg1 PNGS 845:848 PNGS 845:848 PNGS 845:848 Results.: The recipient partner had a shorter V1-V4 region and fewer potential N-linked glycosylation sites (PNGS) than sequences from the source partner. 28419276 0 16 theme Virus 93:97 arg1 Type 99:102 Sexually Transmitted Human Immunodeficiency Virus Type 1 49:104 Sexually Transmitted Human Immunodeficiency Virus Type 1 49:104 Molecular Features of the V1-V4 Coding Region of Sexually Transmitted Human Immunodeficiency Virus Type 1. 28419276 1 17 from number 296:301 arg1 studies 353:359 individual studies 342:359 individual studies 342:359 Background.: Investigations into which human immunodeficiency virus type 1 (HIV-1) sequence features may be selected for transmission during sexual exposure have been hampered by the small number of characterized transmission pairs in individual studies. 28419276 2 18 theme mixed-effects 639:651 arg1 regression 660:669 mixed-effects linear regression 639:669 mixed-effects linear regression 639:669 Methods.: To boost statistical power to detect differences in glycosylation, length, and electrical charge in the HIV-1 V1-V4 coding region, we reanalyzed all available 2485 env sequences derived from 114 subjects representing 58 transmission pairs from previous studies using mixed-effects linear regression and an approach to approximate the unobserved transmitted virus. 28419276 4 19 theme transmitted 965:975 arg1 sequences 977:985 transmitted sequences 965:985 transmitted sequences with source partner and the evolutionary tendency to shorten V1-V4 sequences, reduce the number of PNGS 965:1089 We also detected a trend toward more PNGS and lower isoelectric points in transmitted sequences with source partner and the evolutionary tendency to shorten V1-V4 sequences, reduce the number of PNGS, and lower isoelectric points in the recipient following transmission. 28419276 4 20 dep shorten 1040:1046 arg1 reduce 1065:1070 reduce 1065:1070 reduce the number of PNGS 1065:1089 We also detected a trend toward more PNGS and lower isoelectric points in transmitted sequences with source partner and the evolutionary tendency to shorten V1-V4 sequences, reduce the number of PNGS, and lower isoelectric points in the recipient following transmission. 28419276 5 21 from development 1367:1377 arg1 important 1350:1358 important 1350:1358 important 1350:1358 Conclusions.: By using all available well-characterized env sequences from transmission pairs via sexual exposure, we were able to identify several important virologic factors that may be important in the development of biomedical preventive interventions. 28419276 3 22 from partner 882:888 arg1 sequences 856:864 sequences 856:864 sequences from the source partner 856:888 Results.: The recipient partner had a shorter V1-V4 region and fewer potential N-linked glycosylation sites (PNGS) than sequences from the source partner. 28419276 1 23 theme type 175:178 arg1 features 199:206 human immunodeficiency virus type 1 (HIV-1) sequence features 146:206 human immunodeficiency virus type 1 (HIV-1) sequence features 146:206 Background.: Investigations into which human immunodeficiency virus type 1 (HIV-1) sequence features may be selected for transmission during sexual exposure have been hampered by the small number of characterized transmission pairs in individual studies. 28419276 1 24 from pairs 333:337 arg1 studies 353:359 individual studies 342:359 individual studies 342:359 Background.: Investigations into which human immunodeficiency virus type 1 (HIV-1) sequence features may be selected for transmission during sexual exposure have been hampered by the small number of characterized transmission pairs in individual studies. 28419276 2 25 theme previous 616:623 arg1 studies 625:631 previous studies 616:631 previous studies using mixed-effects linear regression 616:669 Methods.: To boost statistical power to detect differences in glycosylation, length, and electrical charge in the HIV-1 V1-V4 coding region, we reanalyzed all available 2485 env sequences derived from 114 subjects representing 58 transmission pairs from previous studies using mixed-effects linear regression and an approach to approximate the unobserved transmitted virus. 28419276 4 26 theme evolutionary 1015:1026 arg1 tendency 1028:1035 the evolutionary tendency 1011:1035 the evolutionary tendency to shorten V1-V4 sequences, reduce the number of PNGS 1011:1089 We also detected a trend toward more PNGS and lower isoelectric points in transmitted sequences with source partner and the evolutionary tendency to shorten V1-V4 sequences, reduce the number of PNGS, and lower isoelectric points in the recipient following transmission. 28419276 2 27 theme statistical 381:391 arg1 power 393:397 statistical power 381:397 statistical power 381:397 Methods.: To boost statistical power to detect differences in glycosylation, length, and electrical charge in the HIV-1 V1-V4 coding region, we reanalyzed all available 2485 env sequences derived from 114 subjects representing 58 transmission pairs from previous studies using mixed-effects linear regression and an approach to approximate the unobserved transmitted virus. 28419276 4 28 dep tendency 1028:1035 arg1 shorten 1040:1046 shorten 1040:1046 shorten V1-V4 sequences 1040:1062 We also detected a trend toward more PNGS and lower isoelectric points in transmitted sequences with source partner and the evolutionary tendency to shorten V1-V4 sequences, reduce the number of PNGS, and lower isoelectric points in the recipient following transmission. 28419276 2 29 theme coding 488:493 arg1 region 495:500 the HIV-1 V1-V4 coding region 472:500 the HIV-1 V1-V4 coding region 472:500 Methods.: To boost statistical power to detect differences in glycosylation, length, and electrical charge in the HIV-1 V1-V4 coding region, we reanalyzed all available 2485 env sequences derived from 114 subjects representing 58 transmission pairs from previous studies using mixed-effects linear regression and an approach to approximate the unobserved transmitted virus. 28419276 4 30 theme lower 937:941 arg1 points 955:960 lower isoelectric points 937:960 lower isoelectric points 937:960 We also detected a trend toward more PNGS and lower isoelectric points in transmitted sequences with source partner and the evolutionary tendency to shorten V1-V4 sequences, reduce the number of PNGS, and lower isoelectric points in the recipient following transmission. 28419276 2 31 attach derived 550:556 arg1 subjects 567:574 114 subjects 563:574 114 subjects representing 58 transmission pairs from previous studies using mixed-effects linear regression and an approach to approximate the unobserved transmitted virus 563:733 Methods.: To boost statistical power to detect differences in glycosylation, length, and electrical charge in the HIV-1 V1-V4 coding region, we reanalyzed all available 2485 env sequences derived from 114 subjects representing 58 transmission pairs from previous studies using mixed-effects linear regression and an approach to approximate the unobserved transmitted virus. 28419276 2 31 attach derived 550:556 arg2 sequences 540:548 all available 2485 env sequences 517:548 all available 2485 env sequences derived from 114 subjects representing 58 transmission pairs from previous studies using mixed-effects linear regression and an approach to approximate the unobserved transmitted virus 517:733 Methods.: To boost statistical power to detect differences in glycosylation, length, and electrical charge in the HIV-1 V1-V4 coding region, we reanalyzed all available 2485 env sequences derived from 114 subjects representing 58 transmission pairs from previous studies using mixed-effects linear regression and an approach to approximate the unobserved transmitted virus. 28419276 4 32 theme isoelectric 943:953 arg1 points 955:960 lower isoelectric points 937:960 lower isoelectric points 937:960 We also detected a trend toward more PNGS and lower isoelectric points in transmitted sequences with source partner and the evolutionary tendency to shorten V1-V4 sequences, reduce the number of PNGS, and lower isoelectric points in the recipient following transmission. 28419276 0 33 theme Molecular 0:8 arg1 Features 10:17 Molecular Features 0:17 Molecular Features of the V1-V4 Coding Region of Sexually Transmitted Human Immunodeficiency Virus Type 1 0:104 Molecular Features of the V1-V4 Coding Region of Sexually Transmitted Human Immunodeficiency Virus Type 1. 28419276 4 34 with sequences 977:985 arg1 tendency 1028:1035 the evolutionary tendency 1011:1035 the evolutionary tendency to shorten V1-V4 sequences, reduce the number of PNGS 1011:1089 We also detected a trend toward more PNGS and lower isoelectric points in transmitted sequences with source partner and the evolutionary tendency to shorten V1-V4 sequences, reduce the number of PNGS, and lower isoelectric points in the recipient following transmission. 28419276 4 34 with sequences 977:985 arg1 partner 999:1005 source partner 992:1005 source partner 992:1005 We also detected a trend toward more PNGS and lower isoelectric points in transmitted sequences with source partner and the evolutionary tendency to shorten V1-V4 sequences, reduce the number of PNGS, and lower isoelectric points in the recipient following transmission. 28419276 5 35 theme several 1302:1308 arg1 factors 1330:1336 several important virologic factors 1302:1336 several important virologic factors that may be important in the development of biomedical preventive interventions 1302:1416 Conclusions.: By using all available well-characterized env sequences from transmission pairs via sexual exposure, we were able to identify several important virologic factors that may be important in the development of biomedical preventive interventions. 28419276 4 36 from points 1114:1119 arg1 recipient 1128:1136 the recipient 1124:1136 the recipient following transmission 1124:1159 We also detected a trend toward more PNGS and lower isoelectric points in transmitted sequences with source partner and the evolutionary tendency to shorten V1-V4 sequences, reduce the number of PNGS, and lower isoelectric points in the recipient following transmission. 28419276 1 37 from studies 353:359 arg1 number 296:301 the small number 286:301 the small number of characterized transmission pairs in individual studies 286:359 Background.: Investigations into which human immunodeficiency virus type 1 (HIV-1) sequence features may be selected for transmission during sexual exposure have been hampered by the small number of characterized transmission pairs in individual studies. 28419276 2 38 theme env 536:538 arg1 sequences 540:548 all available 2485 env sequences 517:548 all available 2485 env sequences derived from 114 subjects representing 58 transmission pairs from previous studies using mixed-effects linear regression and an approach to approximate the unobserved transmitted virus 517:733 Methods.: To boost statistical power to detect differences in glycosylation, length, and electrical charge in the HIV-1 V1-V4 coding region, we reanalyzed all available 2485 env sequences derived from 114 subjects representing 58 transmission pairs from previous studies using mixed-effects linear regression and an approach to approximate the unobserved transmitted virus. 28419276 3 39 link N-linked 815:822 arg1 sites 838:842 potential N-linked glycosylation sites 805:842 fewer potential N-linked glycosylation sites (PNGS) 799:849 Results.: The recipient partner had a shorter V1-V4 region and fewer potential N-linked glycosylation sites (PNGS) than sequences from the source partner. 28419276 3 39 link N-linked 815:822 arg1 PNGS 845:848 PNGS 845:848 PNGS 845:848 Results.: The recipient partner had a shorter V1-V4 region and fewer potential N-linked glycosylation sites (PNGS) than sequences from the source partner. 28419276 3 40 contain had 768:770 arg1 partner 760:766 The recipient partner 746:766 The recipient partner 746:766 Results.: The recipient partner had a shorter V1-V4 region and fewer potential N-linked glycosylation sites (PNGS) than sequences from the source partner. 28419276 3 40 contain had 768:770 arg2 region 788:793 a shorter V1-V4 region 772:793 a shorter V1-V4 region 772:793 Results.: The recipient partner had a shorter V1-V4 region and fewer potential N-linked glycosylation sites (PNGS) than sequences from the source partner. 28419276 3 40 contain had 768:770 arg2 fewer 799:803 fewer 799:803 fewer 799:803 Results.: The recipient partner had a shorter V1-V4 region and fewer potential N-linked glycosylation sites (PNGS) than sequences from the source partner. 28419276 5 41 theme transmission 1237:1248 arg1 pairs 1250:1254 transmission pairs 1237:1254 transmission pairs 1237:1254 Conclusions.: By using all available well-characterized env sequences from transmission pairs via sexual exposure, we were able to identify several important virologic factors that may be important in the development of biomedical preventive interventions. 28419276 2 42 theme 2485 531:534 arg1 sequences 540:548 all available 2485 env sequences 517:548 all available 2485 env sequences derived from 114 subjects representing 58 transmission pairs from previous studies using mixed-effects linear regression and an approach to approximate the unobserved transmitted virus 517:733 Methods.: To boost statistical power to detect differences in glycosylation, length, and electrical charge in the HIV-1 V1-V4 coding region, we reanalyzed all available 2485 env sequences derived from 114 subjects representing 58 transmission pairs from previous studies using mixed-effects linear regression and an approach to approximate the unobserved transmitted virus. 28419276 4 43 theme more 923:926 arg1 PNGS 928:931 more PNGS 923:931 more PNGS 923:931 We also detected a trend toward more PNGS and lower isoelectric points in transmitted sequences with source partner and the evolutionary tendency to shorten V1-V4 sequences, reduce the number of PNGS, and lower isoelectric points in the recipient following transmission. 28419276 4 44 theme isoelectric 1102:1112 arg1 points 1114:1119 lower isoelectric points 1096:1119 lower isoelectric points in the recipient following transmission 1096:1159 We also detected a trend toward more PNGS and lower isoelectric points in transmitted sequences with source partner and the evolutionary tendency to shorten V1-V4 sequences, reduce the number of PNGS, and lower isoelectric points in the recipient following transmission. 28419276 1 45 theme sequence 190:197 arg1 features 199:206 human immunodeficiency virus type 1 (HIV-1) sequence features 146:206 human immunodeficiency virus type 1 (HIV-1) sequence features 146:206 Background.: Investigations into which human immunodeficiency virus type 1 (HIV-1) sequence features may be selected for transmission during sexual exposure have been hampered by the small number of characterized transmission pairs in individual studies. 28419276 0 46 theme Coding 32:37 arg1 Region 39:44 the V1-V4 Coding Region 22:44 the V1-V4 Coding Region of Sexually Transmitted Human Immunodeficiency Virus Type 1 22:104 Molecular Features of the V1-V4 Coding Region of Sexually Transmitted Human Immunodeficiency Virus Type 1. 28419276 3 47 theme recipient 750:758 arg1 partner 760:766 The recipient partner 746:766 The recipient partner 746:766 Results.: The recipient partner had a shorter V1-V4 region and fewer potential N-linked glycosylation sites (PNGS) than sequences from the source partner. 28419276 2 48 theme available 521:529 arg1 sequences 540:548 all available 2485 env sequences 517:548 all available 2485 env sequences derived from 114 subjects representing 58 transmission pairs from previous studies using mixed-effects linear regression and an approach to approximate the unobserved transmitted virus 517:733 Methods.: To boost statistical power to detect differences in glycosylation, length, and electrical charge in the HIV-1 V1-V4 coding region, we reanalyzed all available 2485 env sequences derived from 114 subjects representing 58 transmission pairs from previous studies using mixed-effects linear regression and an approach to approximate the unobserved transmitted virus. 28419276 3 49 dep fewer 799:803 arg1 sites 838:842 potential N-linked glycosylation sites 805:842 fewer potential N-linked glycosylation sites (PNGS) 799:849 Results.: The recipient partner had a shorter V1-V4 region and fewer potential N-linked glycosylation sites (PNGS) than sequences from the source partner. 28419276 3 49 dep fewer 799:803 arg1 PNGS 845:848 PNGS 845:848 PNGS 845:848 Results.: The recipient partner had a shorter V1-V4 region and fewer potential N-linked glycosylation sites (PNGS) than sequences from the source partner. 28419276 5 50 theme preventive 1393:1402 arg1 interventions 1404:1416 biomedical preventive interventions 1382:1416 biomedical preventive interventions 1382:1416 Conclusions.: By using all available well-characterized env sequences from transmission pairs via sexual exposure, we were able to identify several important virologic factors that may be important in the development of biomedical preventive interventions. 28419276 4 51 theme lower 1096:1100 arg1 points 1114:1119 lower isoelectric points 1096:1119 lower isoelectric points in the recipient following transmission 1096:1159 We also detected a trend toward more PNGS and lower isoelectric points in transmitted sequences with source partner and the evolutionary tendency to shorten V1-V4 sequences, reduce the number of PNGS, and lower isoelectric points in the recipient following transmission. 28419276 5 52 theme well-characterized 1199:1216 arg1 sequences 1222:1230 all available well-characterized env sequences 1185:1230 all available well-characterized env sequences from transmission pairs 1185:1254 Conclusions.: By using all available well-characterized env sequences from transmission pairs via sexual exposure, we were able to identify several important virologic factors that may be important in the development of biomedical preventive interventions. 28419276 0 53 theme V1-V4 26:30 arg1 Region 39:44 the V1-V4 Coding Region 22:44 the V1-V4 Coding Region of Sexually Transmitted Human Immunodeficiency Virus Type 1 22:104 Molecular Features of the V1-V4 Coding Region of Sexually Transmitted Human Immunodeficiency Virus Type 1. 28419276 1 54 theme small 290:294 arg1 number 296:301 the small number 286:301 the small number of characterized transmission pairs in individual studies 286:359 Background.: Investigations into which human immunodeficiency virus type 1 (HIV-1) sequence features may be selected for transmission during sexual exposure have been hampered by the small number of characterized transmission pairs in individual studies. 28419276 4 55 theme source 992:997 arg1 partner 999:1005 source partner 992:1005 source partner 992:1005 We also detected a trend toward more PNGS and lower isoelectric points in transmitted sequences with source partner and the evolutionary tendency to shorten V1-V4 sequences, reduce the number of PNGS, and lower isoelectric points in the recipient following transmission. 28419276 5 56 theme virologic 1320:1328 arg1 factors 1330:1336 several important virologic factors 1302:1336 several important virologic factors that may be important in the development of biomedical preventive interventions 1302:1416 Conclusions.: By using all available well-characterized env sequences from transmission pairs via sexual exposure, we were able to identify several important virologic factors that may be important in the development of biomedical preventive interventions. 28419276 2 57 theme transmitted 717:727 arg1 virus 729:733 the unobserved transmitted virus 702:733 the unobserved transmitted virus 702:733 Methods.: To boost statistical power to detect differences in glycosylation, length, and electrical charge in the HIV-1 V1-V4 coding region, we reanalyzed all available 2485 env sequences derived from 114 subjects representing 58 transmission pairs from previous studies using mixed-effects linear regression and an approach to approximate the unobserved transmitted virus. 28419276 3 58 theme shorter 774:780 arg1 region 788:793 a shorter V1-V4 region 772:793 a shorter V1-V4 region 772:793 Results.: The recipient partner had a shorter V1-V4 region and fewer potential N-linked glycosylation sites (PNGS) than sequences from the source partner. 28419276 2 59 theme electrical 451:460 arg1 charge 462:467 electrical charge 451:467 electrical charge 451:467 Methods.: To boost statistical power to detect differences in glycosylation, length, and electrical charge in the HIV-1 V1-V4 coding region, we reanalyzed all available 2485 env sequences derived from 114 subjects representing 58 transmission pairs from previous studies using mixed-effects linear regression and an approach to approximate the unobserved transmitted virus. 28419276 3 60 theme V1-V4 782:786 arg1 region 788:793 a shorter V1-V4 region 772:793 a shorter V1-V4 region 772:793 Results.: The recipient partner had a shorter V1-V4 region and fewer potential N-linked glycosylation sites (PNGS) than sequences from the source partner. 28419276 5 61 from pairs 1250:1254 arg1 sequences 1222:1230 all available well-characterized env sequences 1185:1230 all available well-characterized env sequences from transmission pairs 1185:1254 Conclusions.: By using all available well-characterized env sequences from transmission pairs via sexual exposure, we were able to identify several important virologic factors that may be important in the development of biomedical preventive interventions. 28419276 3 62 gly glycosylation 824:836 arg2 PNGS 845:848 PNGS 845:848 PNGS 845:848 Results.: The recipient partner had a shorter V1-V4 region and fewer potential N-linked glycosylation sites (PNGS) than sequences from the source partner. 28419276 3 62 gly glycosylation 824:836 arg2 sites 838:842 potential N-linked glycosylation sites 805:842 fewer potential N-linked glycosylation sites (PNGS) 799:849 Results.: The recipient partner had a shorter V1-V4 region and fewer potential N-linked glycosylation sites (PNGS) than sequences from the source partner. 28419276 2 63 theme unobserved 706:715 arg1 virus 729:733 the unobserved transmitted virus 702:733 the unobserved transmitted virus 702:733 Methods.: To boost statistical power to detect differences in glycosylation, length, and electrical charge in the HIV-1 V1-V4 coding region, we reanalyzed all available 2485 env sequences derived from 114 subjects representing 58 transmission pairs from previous studies using mixed-effects linear regression and an approach to approximate the unobserved transmitted virus. 28419276 0 64 theme Region 39:44 arg1 Features 10:17 Molecular Features 0:17 Molecular Features of the V1-V4 Coding Region of Sexually Transmitted Human Immunodeficiency Virus Type 1 0:104 Molecular Features of the V1-V4 Coding Region of Sexually Transmitted Human Immunodeficiency Virus Type 1. 28419276 2 65 from studies 625:631 arg1 approach 678:685 an approach 675:685 an approach to approximate the unobserved transmitted virus 675:733 Methods.: To boost statistical power to detect differences in glycosylation, length, and electrical charge in the HIV-1 V1-V4 coding region, we reanalyzed all available 2485 env sequences derived from 114 subjects representing 58 transmission pairs from previous studies using mixed-effects linear regression and an approach to approximate the unobserved transmitted virus. 28419276 2 65 from studies 625:631 arg1 pairs 605:609 58 transmission pairs 589:609 58 transmission pairs from previous studies using mixed-effects linear regression 589:669 Methods.: To boost statistical power to detect differences in glycosylation, length, and electrical charge in the HIV-1 V1-V4 coding region, we reanalyzed all available 2485 env sequences derived from 114 subjects representing 58 transmission pairs from previous studies using mixed-effects linear regression and an approach to approximate the unobserved transmitted virus. 28419276 5 66 from important 1350:1358 arg1 development 1367:1377 the development 1363:1377 the development of biomedical preventive interventions 1363:1416 Conclusions.: By using all available well-characterized env sequences from transmission pairs via sexual exposure, we were able to identify several important virologic factors that may be important in the development of biomedical preventive interventions. 28419276 5 67 theme interventions 1404:1416 arg1 development 1367:1377 the development 1363:1377 the development of biomedical preventive interventions 1363:1416 Conclusions.: By using all available well-characterized env sequences from transmission pairs via sexual exposure, we were able to identify several important virologic factors that may be important in the development of biomedical preventive interventions. 28419276 1 68 theme characterized 306:318 arg1 pairs 333:337 characterized transmission pairs 306:337 characterized transmission pairs in individual studies 306:359 Background.: Investigations into which human immunodeficiency virus type 1 (HIV-1) sequence features may be selected for transmission during sexual exposure have been hampered by the small number of characterized transmission pairs in individual studies. 28419276 4 69 from sequences 977:985 arg1 recipient 1128:1136 the recipient 1124:1136 the recipient following transmission 1124:1159 We also detected a trend toward more PNGS and lower isoelectric points in transmitted sequences with source partner and the evolutionary tendency to shorten V1-V4 sequences, reduce the number of PNGS, and lower isoelectric points in the recipient following transmission. 28419276 3 70 theme potential 805:813 arg1 sites 838:842 potential N-linked glycosylation sites 805:842 fewer potential N-linked glycosylation sites (PNGS) 799:849 Results.: The recipient partner had a shorter V1-V4 region and fewer potential N-linked glycosylation sites (PNGS) than sequences from the source partner. 28419276 3 70 theme potential 805:813 arg1 PNGS 845:848 PNGS 845:848 PNGS 845:848 Results.: The recipient partner had a shorter V1-V4 region and fewer potential N-linked glycosylation sites (PNGS) than sequences from the source partner. 28419276 5 71 theme biomedical 1382:1391 arg1 interventions 1404:1416 biomedical preventive interventions 1382:1416 biomedical preventive interventions 1382:1416 Conclusions.: By using all available well-characterized env sequences from transmission pairs via sexual exposure, we were able to identify several important virologic factors that may be important in the development of biomedical preventive interventions. 28419276 5 72 theme important 1310:1318 arg1 factors 1330:1336 several important virologic factors 1302:1336 several important virologic factors that may be important in the development of biomedical preventive interventions 1302:1416 Conclusions.: By using all available well-characterized env sequences from transmission pairs via sexual exposure, we were able to identify several important virologic factors that may be important in the development of biomedical preventive interventions. 28419276 4 73 theme PNGS 1086:1089 arg1 number 1076:1081 the number 1072:1081 the number of PNGS 1072:1089 We also detected a trend toward more PNGS and lower isoelectric points in transmitted sequences with source partner and the evolutionary tendency to shorten V1-V4 sequences, reduce the number of PNGS, and lower isoelectric points in the recipient following transmission. 28419276 3 74 theme N-linked 815:822 arg1 sites 838:842 potential N-linked glycosylation sites 805:842 fewer potential N-linked glycosylation sites (PNGS) 799:849 Results.: The recipient partner had a shorter V1-V4 region and fewer potential N-linked glycosylation sites (PNGS) than sequences from the source partner. 28419276 3 74 theme N-linked 815:822 arg1 PNGS 845:848 PNGS 845:848 PNGS 845:848 Results.: The recipient partner had a shorter V1-V4 region and fewer potential N-linked glycosylation sites (PNGS) than sequences from the source partner. 28419276 0 75 theme Transmitted 58:68 arg1 Type 99:102 Sexually Transmitted Human Immunodeficiency Virus Type 1 49:104 Sexually Transmitted Human Immunodeficiency Virus Type 1 49:104 Molecular Features of the V1-V4 Coding Region of Sexually Transmitted Human Immunodeficiency Virus Type 1. 28419276 2 76 theme V1-V4 482:486 arg1 region 495:500 the HIV-1 V1-V4 coding region 472:500 the HIV-1 V1-V4 coding region 472:500 Methods.: To boost statistical power to detect differences in glycosylation, length, and electrical charge in the HIV-1 V1-V4 coding region, we reanalyzed all available 2485 env sequences derived from 114 subjects representing 58 transmission pairs from previous studies using mixed-effects linear regression and an approach to approximate the unobserved transmitted virus. 28419276 1 77 theme transmission 320:331 arg1 pairs 333:337 characterized transmission pairs 306:337 characterized transmission pairs in individual studies 306:359 Background.: Investigations into which human immunodeficiency virus type 1 (HIV-1) sequence features may be selected for transmission during sexual exposure have been hampered by the small number of characterized transmission pairs in individual studies. 28419276 4 78 with points 1114:1119 arg1 tendency 1028:1035 the evolutionary tendency 1011:1035 the evolutionary tendency to shorten V1-V4 sequences, reduce the number of PNGS 1011:1089 We also detected a trend toward more PNGS and lower isoelectric points in transmitted sequences with source partner and the evolutionary tendency to shorten V1-V4 sequences, reduce the number of PNGS, and lower isoelectric points in the recipient following transmission. 28419276 4 78 with points 1114:1119 arg1 partner 999:1005 source partner 992:1005 source partner 992:1005 We also detected a trend toward more PNGS and lower isoelectric points in transmitted sequences with source partner and the evolutionary tendency to shorten V1-V4 sequences, reduce the number of PNGS, and lower isoelectric points in the recipient following transmission. 28419276 5 79 theme env 1218:1220 arg1 sequences 1222:1230 all available well-characterized env sequences 1185:1230 all available well-characterized env sequences from transmission pairs 1185:1254 Conclusions.: By using all available well-characterized env sequences from transmission pairs via sexual exposure, we were able to identify several important virologic factors that may be important in the development of biomedical preventive interventions. 28419276 1 80 theme human 146:150 arg1 type 175:178 human immunodeficiency virus type 1 146:180 human immunodeficiency virus type 1 (HIV-1) sequence features 146:206 Background.: Investigations into which human immunodeficiency virus type 1 (HIV-1) sequence features may be selected for transmission during sexual exposure have been hampered by the small number of characterized transmission pairs in individual studies. 28419276 1 80 theme human 146:150 arg1 HIV-1 183:187 HIV-1 183:187 HIV-1 183:187 Background.: Investigations into which human immunodeficiency virus type 1 (HIV-1) sequence features may be selected for transmission during sexual exposure have been hampered by the small number of characterized transmission pairs in individual studies. 28419276 5 81 theme sexual 1260:1265 arg1 exposure 1267:1274 sexual exposure 1260:1274 sexual exposure 1260:1274 Conclusions.: By using all available well-characterized env sequences from transmission pairs via sexual exposure, we were able to identify several important virologic factors that may be important in the development of biomedical preventive interventions. 27834568 5 0 from glycan 771:776 arg1 H-CDR2 781:786 H-CDR2 781:786 H-CDR2 of 37E1B5 781:796 We show that an N-linked complex-type Fab glycan in H-CDR2 of 37E1B5 is directly involved in the inhibition of latent TGF-β activation. 27834568 6 1 link N-linked 954:961 arg1 glycans 963:969 N-linked glycans 954:969 N-linked glycans 954:969 Removal of the Fab N-glycosylation site by single amino acid substitution, or removal of N-linked glycans by enzymatic digestion, drastically reduced the antibody's ability to inhibit latency-associated peptide (LAP) and αvβ8 association, and TGF-β activation in an αvβ8-mediated TGF-β signaling reporter assay. 27834568 1 2 from responses 156:164 arg1 disease 174:180 lung disease 169:180 lung disease 169:180 Excessive transforming growth factor (TGF)-β is associated with pro-fibrotic responses in lung disease, yet it also plays essential roles in tissue homeostasis and autoimmunity. 27834568 7 3 theme non-competitive 1200:1214 arg1 inhibition 1228:1237 a non-competitive, allosteric inhibition 1198:1237 inhibition 1228:1237 Our results indicate a non-competitive, allosteric inhibition of 37E1B5 on αvβ8-mediated TGF-β activation. 27834568 6 4 gly N-glycosylation 884:898 arg2 site 900:903 the Fab N-glycosylation site 876:903 the Fab N-glycosylation site 876:903 Removal of the Fab N-glycosylation site by single amino acid substitution, or removal of N-linked glycans by enzymatic digestion, drastically reduced the antibody's ability to inhibit latency-associated peptide (LAP) and αvβ8 association, and TGF-β activation in an αvβ8-mediated TGF-β signaling reporter assay. 27834568 6 5 theme glycans 963:969 arg1 removal 943:949 removal 943:949 removal of N-linked glycans by enzymatic digestion 943:992 Removal of the Fab N-glycosylation site by single amino acid substitution, or removal of N-linked glycans by enzymatic digestion, drastically reduced the antibody's ability to inhibit latency-associated peptide (LAP) and αvβ8 association, and TGF-β activation in an αvβ8-mediated TGF-β signaling reporter assay. 27834568 6 5 theme glycans 963:969 arg1 Removal 865:871 Removal 865:871 Removal of the Fab N-glycosylation site by single amino acid substitution 865:937 Removal of the Fab N-glycosylation site by single amino acid substitution, or removal of N-linked glycans by enzymatic digestion, drastically reduced the antibody's ability to inhibit latency-associated peptide (LAP) and αvβ8 association, and TGF-β activation in an αvβ8-mediated TGF-β signaling reporter assay. 27834568 0 6 theme H-CDR2 64:69 arg1 glycan 71:76 its H-CDR2 glycan 60:76 its H-CDR2 glycan 60:76 The TGF-β inhibitory activity of antibody 37E1B5 depends on its H-CDR2 glycan. 27834568 5 7 theme complex-type 754:765 arg1 glycan 771:776 an N-linked complex-type Fab glycan 742:776 an N-linked complex-type Fab glycan in H-CDR2 of 37E1B5 742:796 We show that an N-linked complex-type Fab glycan in H-CDR2 of 37E1B5 is directly involved in the inhibition of latent TGF-β activation. 27834568 2 8 theme activation 339:348 arg1 strategy 426:433 a therapeutic strategy 412:433 a therapeutic strategy for chronic lung diseases 412:459 Therefore, selective inhibition of excessive and aberrant integrin-mediated TGF-β activation via targeting the α-v family of integrins is being pursued as a therapeutic strategy for chronic lung diseases, to mitigate any potential safety concerns with global TGF-β inhibition. 27834568 2 8 theme activation 339:348 arg1 inhibition 278:287 selective inhibition 268:287 selective inhibition of excessive and aberrant integrin-mediated TGF-β activation via targeting the α-v family of integrins 268:390 Therefore, selective inhibition of excessive and aberrant integrin-mediated TGF-β activation via targeting the α-v family of integrins is being pursued as a therapeutic strategy for chronic lung diseases, to mitigate any potential safety concerns with global TGF-β inhibition. 27834568 1 9 theme tissue 220:225 arg1 homeostasis 227:237 tissue homeostasis 220:237 tissue homeostasis 220:237 Excessive transforming growth factor (TGF)-β is associated with pro-fibrotic responses in lung disease, yet it also plays essential roles in tissue homeostasis and autoimmunity. 27834568 2 10 theme global 509:514 arg1 inhibition 522:531 global TGF-β inhibition 509:531 global TGF-β inhibition 509:531 Therefore, selective inhibition of excessive and aberrant integrin-mediated TGF-β activation via targeting the α-v family of integrins is being pursued as a therapeutic strategy for chronic lung diseases, to mitigate any potential safety concerns with global TGF-β inhibition. 27834568 6 11 theme TGF-β 1145:1149 arg1 assay 1170:1174 an αvβ8-mediated TGF-β signaling reporter assay 1128:1174 an αvβ8-mediated TGF-β signaling reporter assay 1128:1174 Removal of the Fab N-glycosylation site by single amino acid substitution, or removal of N-linked glycans by enzymatic digestion, drastically reduced the antibody's ability to inhibit latency-associated peptide (LAP) and αvβ8 association, and TGF-β activation in an αvβ8-mediated TGF-β signaling reporter assay. 27834568 2 12 theme selective 268:276 arg1 strategy 426:433 a therapeutic strategy 412:433 a therapeutic strategy for chronic lung diseases 412:459 Therefore, selective inhibition of excessive and aberrant integrin-mediated TGF-β activation via targeting the α-v family of integrins is being pursued as a therapeutic strategy for chronic lung diseases, to mitigate any potential safety concerns with global TGF-β inhibition. 27834568 2 12 theme selective 268:276 arg1 inhibition 278:287 selective inhibition 268:287 selective inhibition of excessive and aberrant integrin-mediated TGF-β activation via targeting the α-v family of integrins 268:390 Therefore, selective inhibition of excessive and aberrant integrin-mediated TGF-β activation via targeting the α-v family of integrins is being pursued as a therapeutic strategy for chronic lung diseases, to mitigate any potential safety concerns with global TGF-β inhibition. 27834568 4 13 theme cell 714:717 arg1 adhesion 719:726 cell adhesion 714:726 cell adhesion 714:726 This antibody blocks TGF-β activation while not inhibiting cell adhesion. 27834568 6 14 theme αvβ8-mediated 1131:1143 arg1 assay 1170:1174 an αvβ8-mediated TGF-β signaling reporter assay 1128:1174 an αvβ8-mediated TGF-β signaling reporter assay 1128:1174 Removal of the Fab N-glycosylation site by single amino acid substitution, or removal of N-linked glycans by enzymatic digestion, drastically reduced the antibody's ability to inhibit latency-associated peptide (LAP) and αvβ8 association, and TGF-β activation in an αvβ8-mediated TGF-β signaling reporter assay. 27834568 8 15 from lack 1403:1406 arg1 adhesion 1433:1440 cellular adhesion 1424:1440 cellular adhesion by the antibody 1424:1456 This unique, H-CDR2 glycan-mediated mechanism may account for the potent but tolerable TGF-b activation inhibition and lack of an effect on cellular adhesion by the antibody. 27834568 7 16 theme allosteric 1217:1226 arg1 inhibition 1228:1237 a non-competitive, allosteric inhibition 1198:1237 inhibition 1228:1237 Our results indicate a non-competitive, allosteric inhibition of 37E1B5 on αvβ8-mediated TGF-β activation. 27834568 7 17 from inhibition 1228:1237 arg1 activation 1272:1281 αvβ8-mediated TGF-β activation 1252:1281 αvβ8-mediated TGF-β activation 1252:1281 Our results indicate a non-competitive, allosteric inhibition of 37E1B5 on αvβ8-mediated TGF-β activation. 27834568 1 18 theme pro-fibrotic 143:154 arg1 responses 156:164 pro-fibrotic responses 143:164 pro-fibrotic responses in lung disease 143:180 Excessive transforming growth factor (TGF)-β is associated with pro-fibrotic responses in lung disease, yet it also plays essential roles in tissue homeostasis and autoimmunity. 27834568 2 19 theme chronic 439:445 arg1 diseases 452:459 chronic lung diseases 439:459 chronic lung diseases 439:459 Therefore, selective inhibition of excessive and aberrant integrin-mediated TGF-β activation via targeting the α-v family of integrins is being pursued as a therapeutic strategy for chronic lung diseases, to mitigate any potential safety concerns with global TGF-β inhibition. 27834568 5 20 theme N-linked 745:752 arg1 glycan 771:776 an N-linked complex-type Fab glycan 742:776 an N-linked complex-type Fab glycan in H-CDR2 of 37E1B5 742:796 We show that an N-linked complex-type Fab glycan in H-CDR2 of 37E1B5 is directly involved in the inhibition of latent TGF-β activation. 27834568 6 21 theme latency-associated 1049:1066 arg1 LAP 1077:1079 LAP 1077:1079 LAP 1077:1079 Removal of the Fab N-glycosylation site by single amino acid substitution, or removal of N-linked glycans by enzymatic digestion, drastically reduced the antibody's ability to inhibit latency-associated peptide (LAP) and αvβ8 association, and TGF-β activation in an αvβ8-mediated TGF-β signaling reporter assay. 27834568 6 21 theme latency-associated 1049:1066 arg1 peptide 1068:1074 latency-associated peptide 1049:1074 latency-associated peptide (LAP) 1049:1080 Removal of the Fab N-glycosylation site by single amino acid substitution, or removal of N-linked glycans by enzymatic digestion, drastically reduced the antibody's ability to inhibit latency-associated peptide (LAP) and αvβ8 association, and TGF-β activation in an αvβ8-mediated TGF-β signaling reporter assay. 27834568 0 22 theme TGF-β 4:8 arg1 activity 21:28 The TGF-β inhibitory activity 0:28 The TGF-β inhibitory activity of antibody 37E1B5 0:47 The TGF-β inhibitory activity of antibody 37E1B5 depends on its H-CDR2 glycan. 27834568 6 23 theme acid 921:924 arg1 substitution 926:937 single amino acid substitution 908:937 single amino acid substitution 908:937 Removal of the Fab N-glycosylation site by single amino acid substitution, or removal of N-linked glycans by enzymatic digestion, drastically reduced the antibody's ability to inhibit latency-associated peptide (LAP) and αvβ8 association, and TGF-β activation in an αvβ8-mediated TGF-β signaling reporter assay. 27834568 2 24 with safety 488:493 arg1 inhibition 522:531 global TGF-β inhibition 509:531 global TGF-β inhibition 509:531 Therefore, selective inhibition of excessive and aberrant integrin-mediated TGF-β activation via targeting the α-v family of integrins is being pursued as a therapeutic strategy for chronic lung diseases, to mitigate any potential safety concerns with global TGF-β inhibition. 27834568 2 25 theme excessive 292:300 arg1 activation 339:348 excessive and aberrant integrin-mediated TGF-β activation 292:348 activation 339:348 Therefore, selective inhibition of excessive and aberrant integrin-mediated TGF-β activation via targeting the α-v family of integrins is being pursued as a therapeutic strategy for chronic lung diseases, to mitigate any potential safety concerns with global TGF-β inhibition. 27834568 7 26 theme αvβ8-mediated 1252:1264 arg1 activation 1272:1281 αvβ8-mediated TGF-β activation 1252:1281 αvβ8-mediated TGF-β activation 1252:1281 Our results indicate a non-competitive, allosteric inhibition of 37E1B5 on αvβ8-mediated TGF-β activation. 27834568 1 27 theme Excessive 79:87 arg1 TGF 117:119 TGF 117:119 TGF 117:119 Excessive transforming growth factor (TGF)-β is associated with pro-fibrotic responses in lung disease, yet it also plays essential roles in tissue homeostasis and autoimmunity. 27834568 1 27 theme Excessive 79:87 arg1 factor 109:114 Excessive transforming growth factor 79:114 Excessive transforming growth factor (TGF) 79:120 Excessive transforming growth factor (TGF)-β is associated with pro-fibrotic responses in lung disease, yet it also plays essential roles in tissue homeostasis and autoimmunity. 27834568 8 28 from effect 1414:1419 arg1 adhesion 1433:1440 cellular adhesion 1424:1440 cellular adhesion by the antibody 1424:1456 This unique, H-CDR2 glycan-mediated mechanism may account for the potent but tolerable TGF-b activation inhibition and lack of an effect on cellular adhesion by the antibody. 27834568 1 29 theme lung 169:172 arg1 disease 174:180 lung disease 169:180 lung disease 169:180 Excessive transforming growth factor (TGF)-β is associated with pro-fibrotic responses in lung disease, yet it also plays essential roles in tissue homeostasis and autoimmunity. 27834568 2 30 theme therapeutic 414:424 arg1 strategy 426:433 a therapeutic strategy 412:433 a therapeutic strategy for chronic lung diseases 412:459 Therefore, selective inhibition of excessive and aberrant integrin-mediated TGF-β activation via targeting the α-v family of integrins is being pursued as a therapeutic strategy for chronic lung diseases, to mitigate any potential safety concerns with global TGF-β inhibition. 27834568 2 30 theme therapeutic 414:424 arg1 inhibition 278:287 selective inhibition 268:287 selective inhibition of excessive and aberrant integrin-mediated TGF-β activation via targeting the α-v family of integrins 268:390 Therefore, selective inhibition of excessive and aberrant integrin-mediated TGF-β activation via targeting the α-v family of integrins is being pursued as a therapeutic strategy for chronic lung diseases, to mitigate any potential safety concerns with global TGF-β inhibition. 27834568 8 31 theme effect 1414:1419 arg1 activation 1377:1386 the potent but tolerable TGF-b activation inhibition and lack of an effect on cellular adhesion by the antibody 1346:1456 activation 1377:1386 This unique, H-CDR2 glycan-mediated mechanism may account for the potent but tolerable TGF-b activation inhibition and lack of an effect on cellular adhesion by the antibody. 27834568 8 31 theme effect 1414:1419 arg1 lack 1403:1406 lack 1403:1406 lack of an effect on cellular adhesion by the antibody 1403:1456 This unique, H-CDR2 glycan-mediated mechanism may account for the potent but tolerable TGF-b activation inhibition and lack of an effect on cellular adhesion by the antibody. 27834568 8 32 dep activation 1377:1386 arg1 inhibition 1388:1397 inhibition 1388:1397 inhibition 1388:1397 This unique, H-CDR2 glycan-mediated mechanism may account for the potent but tolerable TGF-b activation inhibition and lack of an effect on cellular adhesion by the antibody. 27834568 1 33 theme transforming 89:100 arg1 TGF 117:119 TGF 117:119 TGF 117:119 Excessive transforming growth factor (TGF)-β is associated with pro-fibrotic responses in lung disease, yet it also plays essential roles in tissue homeostasis and autoimmunity. 27834568 1 33 theme transforming 89:100 arg1 factor 109:114 Excessive transforming growth factor 79:114 Excessive transforming growth factor (TGF) 79:120 Excessive transforming growth factor (TGF)-β is associated with pro-fibrotic responses in lung disease, yet it also plays essential roles in tissue homeostasis and autoimmunity. 27834568 8 34 theme unique 1289:1294 arg1 mechanism 1320:1328 This unique, H-CDR2 glycan-mediated mechanism 1284:1328 This unique, H-CDR2 glycan-mediated mechanism 1284:1328 This unique, H-CDR2 glycan-mediated mechanism may account for the potent but tolerable TGF-b activation inhibition and lack of an effect on cellular adhesion by the antibody. 27834568 0 35 theme inhibitory 10:19 arg1 activity 21:28 The TGF-β inhibitory activity 0:28 The TGF-β inhibitory activity of antibody 37E1B5 0:47 The TGF-β inhibitory activity of antibody 37E1B5 depends on its H-CDR2 glycan. 27834568 2 36 dep safety 488:493 arg1 concerns 495:502 concerns 495:502 concerns 495:502 Therefore, selective inhibition of excessive and aberrant integrin-mediated TGF-β activation via targeting the α-v family of integrins is being pursued as a therapeutic strategy for chronic lung diseases, to mitigate any potential safety concerns with global TGF-β inhibition. 27834568 8 37 theme cellular 1424:1431 arg1 adhesion 1433:1440 cellular adhesion 1424:1440 cellular adhesion by the antibody 1424:1456 This unique, H-CDR2 glycan-mediated mechanism may account for the potent but tolerable TGF-b activation inhibition and lack of an effect on cellular adhesion by the antibody. 27834568 1 38 theme growth 102:107 arg1 TGF 117:119 TGF 117:119 TGF 117:119 Excessive transforming growth factor (TGF)-β is associated with pro-fibrotic responses in lung disease, yet it also plays essential roles in tissue homeostasis and autoimmunity. 27834568 1 38 theme growth 102:107 arg1 factor 109:114 Excessive transforming growth factor 79:114 Excessive transforming growth factor (TGF) 79:120 Excessive transforming growth factor (TGF)-β is associated with pro-fibrotic responses in lung disease, yet it also plays essential roles in tissue homeostasis and autoimmunity. 27834568 6 39 theme Fab 880:882 arg1 site 900:903 the Fab N-glycosylation site 876:903 the Fab N-glycosylation site 876:903 Removal of the Fab N-glycosylation site by single amino acid substitution, or removal of N-linked glycans by enzymatic digestion, drastically reduced the antibody's ability to inhibit latency-associated peptide (LAP) and αvβ8 association, and TGF-β activation in an αvβ8-mediated TGF-β signaling reporter assay. 27834568 6 40 theme TGF-β 1108:1112 arg1 activation 1114:1123 TGF-β activation 1108:1123 TGF-β activation in an αvβ8-mediated TGF-β signaling reporter assay 1108:1174 Removal of the Fab N-glycosylation site by single amino acid substitution, or removal of N-linked glycans by enzymatic digestion, drastically reduced the antibody's ability to inhibit latency-associated peptide (LAP) and αvβ8 association, and TGF-β activation in an αvβ8-mediated TGF-β signaling reporter assay. 27834568 0 41 theme antibody 33:40 arg1 37E1B5 42:47 antibody 37E1B5 33:47 antibody 37E1B5 33:47 The TGF-β inhibitory activity of antibody 37E1B5 depends on its H-CDR2 glycan. 27834568 4 42 theme TGF-β 676:680 arg1 activation 682:691 TGF-β activation 676:691 TGF-β activation 676:691 This antibody blocks TGF-β activation while not inhibiting cell adhesion. 27834568 3 43 theme αvβ8 622:625 arg1 antibody 637:644 an αvβ8 targeting antibody 619:644 an αvβ8 targeting antibody 619:644 In this work, we reveal a novel mechanism of inhibiting TGF-β activation utilized by an αvβ8 targeting antibody, 37E1B5. 27834568 3 43 theme αvβ8 622:625 arg1 37E1B5 647:652 37E1B5 647:652 37E1B5 647:652 In this work, we reveal a novel mechanism of inhibiting TGF-β activation utilized by an αvβ8 targeting antibody, 37E1B5. 27834568 3 44 theme novel 560:564 arg1 mechanism 566:574 a novel mechanism 558:574 a novel mechanism of inhibiting TGF-β activation utilized by an αvβ8 targeting antibody, 37E1B5 558:652 In this work, we reveal a novel mechanism of inhibiting TGF-β activation utilized by an αvβ8 targeting antibody, 37E1B5. 27834568 2 45 theme α-v 368:370 arg1 family 372:377 the α-v family 364:377 the α-v family of integrins 364:390 Therefore, selective inhibition of excessive and aberrant integrin-mediated TGF-β activation via targeting the α-v family of integrins is being pursued as a therapeutic strategy for chronic lung diseases, to mitigate any potential safety concerns with global TGF-β inhibition. 27834568 7 46 theme TGF-β 1266:1270 arg1 activation 1272:1281 αvβ8-mediated TGF-β activation 1252:1281 αvβ8-mediated TGF-β activation 1252:1281 Our results indicate a non-competitive, allosteric inhibition of 37E1B5 on αvβ8-mediated TGF-β activation. 27834568 2 47 theme integrins 382:390 arg1 family 372:377 the α-v family 364:377 the α-v family of integrins 364:390 Therefore, selective inhibition of excessive and aberrant integrin-mediated TGF-β activation via targeting the α-v family of integrins is being pursued as a therapeutic strategy for chronic lung diseases, to mitigate any potential safety concerns with global TGF-β inhibition. 27834568 6 48 theme amino 915:919 arg1 substitution 926:937 single amino acid substitution 908:937 single amino acid substitution 908:937 Removal of the Fab N-glycosylation site by single amino acid substitution, or removal of N-linked glycans by enzymatic digestion, drastically reduced the antibody's ability to inhibit latency-associated peptide (LAP) and αvβ8 association, and TGF-β activation in an αvβ8-mediated TGF-β signaling reporter assay. 27834568 2 49 theme TGF-β 516:520 arg1 inhibition 522:531 global TGF-β inhibition 509:531 global TGF-β inhibition 509:531 Therefore, selective inhibition of excessive and aberrant integrin-mediated TGF-β activation via targeting the α-v family of integrins is being pursued as a therapeutic strategy for chronic lung diseases, to mitigate any potential safety concerns with global TGF-β inhibition. 27834568 6 50 theme N-linked 954:961 arg1 glycans 963:969 N-linked glycans 954:969 N-linked glycans 954:969 Removal of the Fab N-glycosylation site by single amino acid substitution, or removal of N-linked glycans by enzymatic digestion, drastically reduced the antibody's ability to inhibit latency-associated peptide (LAP) and αvβ8 association, and TGF-β activation in an αvβ8-mediated TGF-β signaling reporter assay. 27834568 6 51 theme enzymatic 974:982 arg1 digestion 984:992 enzymatic digestion 974:992 enzymatic digestion 974:992 Removal of the Fab N-glycosylation site by single amino acid substitution, or removal of N-linked glycans by enzymatic digestion, drastically reduced the antibody's ability to inhibit latency-associated peptide (LAP) and αvβ8 association, and TGF-β activation in an αvβ8-mediated TGF-β signaling reporter assay. 27834568 6 52 theme site 900:903 arg1 removal 943:949 removal 943:949 removal of N-linked glycans by enzymatic digestion 943:992 Removal of the Fab N-glycosylation site by single amino acid substitution, or removal of N-linked glycans by enzymatic digestion, drastically reduced the antibody's ability to inhibit latency-associated peptide (LAP) and αvβ8 association, and TGF-β activation in an αvβ8-mediated TGF-β signaling reporter assay. 27834568 6 52 theme site 900:903 arg1 Removal 865:871 Removal 865:871 Removal of the Fab N-glycosylation site by single amino acid substitution 865:937 Removal of the Fab N-glycosylation site by single amino acid substitution, or removal of N-linked glycans by enzymatic digestion, drastically reduced the antibody's ability to inhibit latency-associated peptide (LAP) and αvβ8 association, and TGF-β activation in an αvβ8-mediated TGF-β signaling reporter assay. 27834568 2 53 theme lung 447:450 arg1 diseases 452:459 chronic lung diseases 439:459 chronic lung diseases 439:459 Therefore, selective inhibition of excessive and aberrant integrin-mediated TGF-β activation via targeting the α-v family of integrins is being pursued as a therapeutic strategy for chronic lung diseases, to mitigate any potential safety concerns with global TGF-β inhibition. 27834568 6 54 theme single 908:913 arg1 substitution 926:937 single amino acid substitution 908:937 single amino acid substitution 908:937 Removal of the Fab N-glycosylation site by single amino acid substitution, or removal of N-linked glycans by enzymatic digestion, drastically reduced the antibody's ability to inhibit latency-associated peptide (LAP) and αvβ8 association, and TGF-β activation in an αvβ8-mediated TGF-β signaling reporter assay. 27834568 8 55 theme potent 1350:1355 arg1 activation 1377:1386 the potent but tolerable TGF-b activation inhibition and lack of an effect on cellular adhesion by the antibody 1346:1456 activation 1377:1386 This unique, H-CDR2 glycan-mediated mechanism may account for the potent but tolerable TGF-b activation inhibition and lack of an effect on cellular adhesion by the antibody. 27834568 8 56 from adhesion 1433:1440 arg1 activation 1377:1386 the potent but tolerable TGF-b activation inhibition and lack of an effect on cellular adhesion by the antibody 1346:1456 activation 1377:1386 This unique, H-CDR2 glycan-mediated mechanism may account for the potent but tolerable TGF-b activation inhibition and lack of an effect on cellular adhesion by the antibody. 27834568 8 56 from adhesion 1433:1440 arg1 lack 1403:1406 lack 1403:1406 lack of an effect on cellular adhesion by the antibody 1403:1456 This unique, H-CDR2 glycan-mediated mechanism may account for the potent but tolerable TGF-b activation inhibition and lack of an effect on cellular adhesion by the antibody. 27834568 5 57 link N-linked 745:752 arg1 glycan 771:776 an N-linked complex-type Fab glycan 742:776 an N-linked complex-type Fab glycan in H-CDR2 of 37E1B5 742:796 We show that an N-linked complex-type Fab glycan in H-CDR2 of 37E1B5 is directly involved in the inhibition of latent TGF-β activation. 27834568 2 58 theme TGF-β 333:337 arg1 activation 339:348 excessive and aberrant integrin-mediated TGF-β activation 292:348 activation 339:348 Therefore, selective inhibition of excessive and aberrant integrin-mediated TGF-β activation via targeting the α-v family of integrins is being pursued as a therapeutic strategy for chronic lung diseases, to mitigate any potential safety concerns with global TGF-β inhibition. 27834568 0 59 theme 37E1B5 42:47 arg1 activity 21:28 The TGF-β inhibitory activity 0:28 The TGF-β inhibitory activity of antibody 37E1B5 0:47 The TGF-β inhibitory activity of antibody 37E1B5 depends on its H-CDR2 glycan. 27834568 6 60 from activation 1114:1123 arg1 assay 1170:1174 an αvβ8-mediated TGF-β signaling reporter assay 1128:1174 an αvβ8-mediated TGF-β signaling reporter assay 1128:1174 Removal of the Fab N-glycosylation site by single amino acid substitution, or removal of N-linked glycans by enzymatic digestion, drastically reduced the antibody's ability to inhibit latency-associated peptide (LAP) and αvβ8 association, and TGF-β activation in an αvβ8-mediated TGF-β signaling reporter assay. 27834568 8 61 dep unique 1289:1294 arg1 glycan-mediated 1304:1318 glycan-mediated 1304:1318 glycan-mediated 1304:1318 This unique, H-CDR2 glycan-mediated mechanism may account for the potent but tolerable TGF-b activation inhibition and lack of an effect on cellular adhesion by the antibody. 27834568 6 62 from association 1091:1101 arg1 assay 1170:1174 an αvβ8-mediated TGF-β signaling reporter assay 1128:1174 an αvβ8-mediated TGF-β signaling reporter assay 1128:1174 Removal of the Fab N-glycosylation site by single amino acid substitution, or removal of N-linked glycans by enzymatic digestion, drastically reduced the antibody's ability to inhibit latency-associated peptide (LAP) and αvβ8 association, and TGF-β activation in an αvβ8-mediated TGF-β signaling reporter assay. 27834568 2 63 theme integrin-mediated 315:331 arg1 activation 339:348 excessive and aberrant integrin-mediated TGF-β activation 292:348 activation 339:348 Therefore, selective inhibition of excessive and aberrant integrin-mediated TGF-β activation via targeting the α-v family of integrins is being pursued as a therapeutic strategy for chronic lung diseases, to mitigate any potential safety concerns with global TGF-β inhibition. 27834568 6 64 theme signaling 1151:1159 arg1 assay 1170:1174 an αvβ8-mediated TGF-β signaling reporter assay 1128:1174 an αvβ8-mediated TGF-β signaling reporter assay 1128:1174 Removal of the Fab N-glycosylation site by single amino acid substitution, or removal of N-linked glycans by enzymatic digestion, drastically reduced the antibody's ability to inhibit latency-associated peptide (LAP) and αvβ8 association, and TGF-β activation in an αvβ8-mediated TGF-β signaling reporter assay. 27834568 3 65 theme TGF-β 590:594 arg1 activation 596:605 TGF-β activation 590:605 TGF-β activation utilized by an αvβ8 targeting antibody, 37E1B5 590:652 In this work, we reveal a novel mechanism of inhibiting TGF-β activation utilized by an αvβ8 targeting antibody, 37E1B5. 27834568 8 66 theme TGF-b 1371:1375 arg1 activation 1377:1386 the potent but tolerable TGF-b activation inhibition and lack of an effect on cellular adhesion by the antibody 1346:1456 activation 1377:1386 This unique, H-CDR2 glycan-mediated mechanism may account for the potent but tolerable TGF-b activation inhibition and lack of an effect on cellular adhesion by the antibody. 27834568 2 67 theme aberrant 306:313 arg1 activation 339:348 excessive and aberrant integrin-mediated TGF-β activation 292:348 activation 339:348 Therefore, selective inhibition of excessive and aberrant integrin-mediated TGF-β activation via targeting the α-v family of integrins is being pursued as a therapeutic strategy for chronic lung diseases, to mitigate any potential safety concerns with global TGF-β inhibition. 27834568 5 68 theme latent 840:845 arg1 activation 853:862 latent TGF-β activation 840:862 latent TGF-β activation 840:862 We show that an N-linked complex-type Fab glycan in H-CDR2 of 37E1B5 is directly involved in the inhibition of latent TGF-β activation. 27834568 3 69 theme targeting 627:635 arg1 antibody 637:644 an αvβ8 targeting antibody 619:644 an αvβ8 targeting antibody 619:644 In this work, we reveal a novel mechanism of inhibiting TGF-β activation utilized by an αvβ8 targeting antibody, 37E1B5. 27834568 3 69 theme targeting 627:635 arg1 37E1B5 647:652 37E1B5 647:652 37E1B5 647:652 In this work, we reveal a novel mechanism of inhibiting TGF-β activation utilized by an αvβ8 targeting antibody, 37E1B5. 27834568 7 70 theme 37E1B5 1242:1247 arg1 inhibition 1228:1237 a non-competitive, allosteric inhibition 1198:1237 inhibition 1228:1237 Our results indicate a non-competitive, allosteric inhibition of 37E1B5 on αvβ8-mediated TGF-β activation. 27834568 8 71 from activation 1377:1386 arg1 adhesion 1433:1440 cellular adhesion 1424:1440 cellular adhesion by the antibody 1424:1456 This unique, H-CDR2 glycan-mediated mechanism may account for the potent but tolerable TGF-b activation inhibition and lack of an effect on cellular adhesion by the antibody. 27834568 2 72 theme potential 478:486 arg1 safety 488:493 any potential safety concerns 474:502 any potential safety concerns with global TGF-β inhibition 474:531 Therefore, selective inhibition of excessive and aberrant integrin-mediated TGF-β activation via targeting the α-v family of integrins is being pursued as a therapeutic strategy for chronic lung diseases, to mitigate any potential safety concerns with global TGF-β inhibition. 27834568 8 73 theme tolerable 1361:1369 arg1 activation 1377:1386 the potent but tolerable TGF-b activation inhibition and lack of an effect on cellular adhesion by the antibody 1346:1456 activation 1377:1386 This unique, H-CDR2 glycan-mediated mechanism may account for the potent but tolerable TGF-b activation inhibition and lack of an effect on cellular adhesion by the antibody. 27834568 6 74 theme reporter 1161:1168 arg1 assay 1170:1174 an αvβ8-mediated TGF-β signaling reporter assay 1128:1174 an αvβ8-mediated TGF-β signaling reporter assay 1128:1174 Removal of the Fab N-glycosylation site by single amino acid substitution, or removal of N-linked glycans by enzymatic digestion, drastically reduced the antibody's ability to inhibit latency-associated peptide (LAP) and αvβ8 association, and TGF-β activation in an αvβ8-mediated TGF-β signaling reporter assay. 27834568 5 75 theme TGF-β 847:851 arg1 activation 853:862 latent TGF-β activation 840:862 latent TGF-β activation 840:862 We show that an N-linked complex-type Fab glycan in H-CDR2 of 37E1B5 is directly involved in the inhibition of latent TGF-β activation. 27834568 1 76 theme essential 201:209 arg1 roles 211:215 essential roles 201:215 essential roles 201:215 Excessive transforming growth factor (TGF)-β is associated with pro-fibrotic responses in lung disease, yet it also plays essential roles in tissue homeostasis and autoimmunity. 27834568 5 77 theme Fab 767:769 arg1 glycan 771:776 an N-linked complex-type Fab glycan 742:776 an N-linked complex-type Fab glycan in H-CDR2 of 37E1B5 742:796 We show that an N-linked complex-type Fab glycan in H-CDR2 of 37E1B5 is directly involved in the inhibition of latent TGF-β activation. 27834568 6 78 theme N-glycosylation 884:898 arg1 site 900:903 the Fab N-glycosylation site 876:903 the Fab N-glycosylation site 876:903 Removal of the Fab N-glycosylation site by single amino acid substitution, or removal of N-linked glycans by enzymatic digestion, drastically reduced the antibody's ability to inhibit latency-associated peptide (LAP) and αvβ8 association, and TGF-β activation in an αvβ8-mediated TGF-β signaling reporter assay. 27834568 5 79 theme 37E1B5 791:796 arg1 H-CDR2 781:786 H-CDR2 781:786 H-CDR2 of 37E1B5 781:796 We show that an N-linked complex-type Fab glycan in H-CDR2 of 37E1B5 is directly involved in the inhibition of latent TGF-β activation. 27834568 5 80 theme activation 853:862 arg1 inhibition 826:835 the inhibition 822:835 the inhibition of latent TGF-β activation 822:862 We show that an N-linked complex-type Fab glycan in H-CDR2 of 37E1B5 is directly involved in the inhibition of latent TGF-β activation. 29115822 8 0 from application 1794:1804 arg1 discovery 1814:1822 drug discovery 1809:1822 drug discovery 1809:1822 Moreover, this method can be used for enzyme kinetic analysis, quantitative detection of cellular OGT activity, and the screening of OGT inhibitors, holding great potential for further application in drug discovery and clinical diagnosis. 29115822 8 0 from application 1794:1804 arg1 diagnosis 1837:1845 clinical diagnosis 1828:1845 clinical diagnosis 1828:1845 Moreover, this method can be used for enzyme kinetic analysis, quantitative detection of cellular OGT activity, and the screening of OGT inhibitors, holding great potential for further application in drug discovery and clinical diagnosis. 29115822 0 1 theme Activity 84:91 arg1 Detection 50:58 Sensitive Detection 40:58 Sensitive Detection of O-GlcNAc Transferase Activity 40:91 Single Quantum Dot-Based Nanosensor for Sensitive Detection of O-GlcNAc Transferase Activity. 29115822 6 2 theme single-molecule 1294:1308 arg1 detection 1310:1318 single-molecule detection 1294:1318 single-molecule detection 1294:1318 The resultant glycosylated Cy5/biotin-modified peptides may assemble on the surface of the streptavidin-coated QD to obtain a QD-peptide-Cy5 nanostructure in which the fluorescence resonance energy transfer (FRET) from the QD to Cy5 can occur, leading to the emission of Cy5 which can be quantified by single-molecule detection. 29115822 8 3 dep inhibitors 1746:1755 arg1 holding 1758:1764 holding 1758:1764 holding great potential for further application in drug discovery and clinical diagnosis 1758:1845 Moreover, this method can be used for enzyme kinetic analysis, quantitative detection of cellular OGT activity, and the screening of OGT inhibitors, holding great potential for further application in drug discovery and clinical diagnosis. 29115822 6 4 theme energy 1183:1188 arg1 FRET 1200:1203 FRET 1200:1203 FRET 1200:1203 The resultant glycosylated Cy5/biotin-modified peptides may assemble on the surface of the streptavidin-coated QD to obtain a QD-peptide-Cy5 nanostructure in which the fluorescence resonance energy transfer (FRET) from the QD to Cy5 can occur, leading to the emission of Cy5 which can be quantified by single-molecule detection. 29115822 6 4 theme energy 1183:1188 arg1 transfer 1190:1197 the fluorescence resonance energy transfer 1156:1197 the fluorescence resonance energy transfer (FRET) from the QD to Cy5 1156:1223 The resultant glycosylated Cy5/biotin-modified peptides may assemble on the surface of the streptavidin-coated QD to obtain a QD-peptide-Cy5 nanostructure in which the fluorescence resonance energy transfer (FRET) from the QD to Cy5 can occur, leading to the emission of Cy5 which can be quantified by single-molecule detection. 29115822 8 5 theme OGT 1707:1709 arg1 activity 1711:1718 cellular OGT activity 1698:1718 cellular OGT activity 1698:1718 Moreover, this method can be used for enzyme kinetic analysis, quantitative detection of cellular OGT activity, and the screening of OGT inhibitors, holding great potential for further application in drug discovery and clinical diagnosis. 29115822 4 6 theme Cy5/biotin-modified 587:605 arg1 peptide 607:613 a Cy5/biotin-modified peptide 585:613 a Cy5/biotin-modified peptide with a serine hydroxyl group 585:642 We design a Cy5/biotin-modified peptide with a serine hydroxyl group for sensing OGT and a protease site adjacent to the glycosylation site for proteinase cleavage, with a universal nonradioactive UDP-GlcNAc as the sugar donor and a Cy5/biotin-modified peptide as the substrate. 29115822 7 7 theme enzyme 1477:1482 arg1 purification 1484:1495 any enzyme purification 1473:1495 any enzyme purification 1473:1495 This method exhibits high sensitivity with a limit of detection of 3.47 × 10-13 M, and it is very simple and straightforward without the involvement of any enzyme purification, radioisotope-labeled sugar donors, specific antibodies, and the synthesis of fluorescent UDP-GlcNAc analogues. 29115822 8 8 theme quantitative 1672:1683 arg1 detection 1685:1693 quantitative detection 1672:1693 quantitative detection of cellular OGT activity 1672:1718 Moreover, this method can be used for enzyme kinetic analysis, quantitative detection of cellular OGT activity, and the screening of OGT inhibitors, holding great potential for further application in drug discovery and clinical diagnosis. 29115822 8 9 theme drug 1809:1812 arg1 discovery 1814:1822 drug discovery 1809:1822 drug discovery 1809:1822 Moreover, this method can be used for enzyme kinetic analysis, quantitative detection of cellular OGT activity, and the screening of OGT inhibitors, holding great potential for further application in drug discovery and clinical diagnosis. 29115822 2 10 theme responsible 324:334 arg1 enzyme 317:322 an intracellular enzyme 300:322 an intracellular enzyme responsible for O-linked N-acetylglucosamine (O-GlcNAc) glycosylation 300:392 Human O-GlcNAc transferase (OGT) is an intracellular enzyme responsible for O-linked N-acetylglucosamine (O-GlcNAc) glycosylation, and the deregulation of OGT activity occurs in cancer, diabetes, and neurodegenerative disease. 29115822 2 10 theme responsible 324:334 arg1 transferase 279:289 Human O-GlcNAc transferase 264:289 Human O-GlcNAc transferase (OGT) 264:295 Human O-GlcNAc transferase (OGT) is an intracellular enzyme responsible for O-linked N-acetylglucosamine (O-GlcNAc) glycosylation, and the deregulation of OGT activity occurs in cancer, diabetes, and neurodegenerative disease. 29115822 5 11 theme protease-protection 963:981 arg1 peptide 983:989 a protease-protection peptide 961:989 a protease-protection peptide 961:989 In the presence of OGT, it catalyzes the glycosylation reaction to generate a glycosylated peptide that is a protease-protection peptide. 29115822 5 11 theme protease-protection 963:981 arg1 peptide 945:951 a glycosylated peptide 930:951 a glycosylated peptide that is a protease-protection peptide 930:989 In the presence of OGT, it catalyzes the glycosylation reaction to generate a glycosylated peptide that is a protease-protection peptide. 29115822 6 12 theme Cy5/biotin-modified 1019:1037 arg1 peptides 1039:1046 The resultant glycosylated Cy5/biotin-modified peptides 992:1046 The resultant glycosylated Cy5/biotin-modified peptides 992:1046 The resultant glycosylated Cy5/biotin-modified peptides may assemble on the surface of the streptavidin-coated QD to obtain a QD-peptide-Cy5 nanostructure in which the fluorescence resonance energy transfer (FRET) from the QD to Cy5 can occur, leading to the emission of Cy5 which can be quantified by single-molecule detection. 29115822 4 13 theme universal 747:755 arg1 UDP-GlcNAc 772:781 a universal nonradioactive UDP-GlcNAc 745:781 a universal nonradioactive UDP-GlcNAc as the sugar donor 745:800 We design a Cy5/biotin-modified peptide with a serine hydroxyl group for sensing OGT and a protease site adjacent to the glycosylation site for proteinase cleavage, with a universal nonradioactive UDP-GlcNAc as the sugar donor and a Cy5/biotin-modified peptide as the substrate. 29115822 8 14 theme clinical 1828:1835 arg1 diagnosis 1837:1845 clinical diagnosis 1828:1845 clinical diagnosis 1828:1845 Moreover, this method can be used for enzyme kinetic analysis, quantitative detection of cellular OGT activity, and the screening of OGT inhibitors, holding great potential for further application in drug discovery and clinical diagnosis. 29115822 6 15 from QD 1215:1216 arg1 FRET 1200:1203 FRET 1200:1203 FRET 1200:1203 The resultant glycosylated Cy5/biotin-modified peptides may assemble on the surface of the streptavidin-coated QD to obtain a QD-peptide-Cy5 nanostructure in which the fluorescence resonance energy transfer (FRET) from the QD to Cy5 can occur, leading to the emission of Cy5 which can be quantified by single-molecule detection. 29115822 6 15 from QD 1215:1216 arg1 transfer 1190:1197 the fluorescence resonance energy transfer 1156:1197 the fluorescence resonance energy transfer (FRET) from the QD to Cy5 1156:1223 The resultant glycosylated Cy5/biotin-modified peptides may assemble on the surface of the streptavidin-coated QD to obtain a QD-peptide-Cy5 nanostructure in which the fluorescence resonance energy transfer (FRET) from the QD to Cy5 can occur, leading to the emission of Cy5 which can be quantified by single-molecule detection. 29115822 6 16 theme fluorescence 1160:1171 arg1 FRET 1200:1203 FRET 1200:1203 FRET 1200:1203 The resultant glycosylated Cy5/biotin-modified peptides may assemble on the surface of the streptavidin-coated QD to obtain a QD-peptide-Cy5 nanostructure in which the fluorescence resonance energy transfer (FRET) from the QD to Cy5 can occur, leading to the emission of Cy5 which can be quantified by single-molecule detection. 29115822 6 16 theme fluorescence 1160:1171 arg1 transfer 1190:1197 the fluorescence resonance energy transfer 1156:1197 the fluorescence resonance energy transfer (FRET) from the QD to Cy5 1156:1223 The resultant glycosylated Cy5/biotin-modified peptides may assemble on the surface of the streptavidin-coated QD to obtain a QD-peptide-Cy5 nanostructure in which the fluorescence resonance energy transfer (FRET) from the QD to Cy5 can occur, leading to the emission of Cy5 which can be quantified by single-molecule detection. 29115822 8 17 theme great 1766:1770 arg1 potential 1772:1780 great potential 1766:1780 great potential 1766:1780 Moreover, this method can be used for enzyme kinetic analysis, quantitative detection of cellular OGT activity, and the screening of OGT inhibitors, holding great potential for further application in drug discovery and clinical diagnosis. 29115822 6 18 theme streptavidin-coated 1083:1101 arg1 QD 1103:1104 the streptavidin-coated QD 1079:1104 the streptavidin-coated QD 1079:1104 The resultant glycosylated Cy5/biotin-modified peptides may assemble on the surface of the streptavidin-coated QD to obtain a QD-peptide-Cy5 nanostructure in which the fluorescence resonance energy transfer (FRET) from the QD to Cy5 can occur, leading to the emission of Cy5 which can be quantified by single-molecule detection. 29115822 2 19 theme intracellular 303:315 arg1 enzyme 317:322 an intracellular enzyme 300:322 an intracellular enzyme responsible for O-linked N-acetylglucosamine (O-GlcNAc) glycosylation 300:392 Human O-GlcNAc transferase (OGT) is an intracellular enzyme responsible for O-linked N-acetylglucosamine (O-GlcNAc) glycosylation, and the deregulation of OGT activity occurs in cancer, diabetes, and neurodegenerative disease. 29115822 2 19 theme intracellular 303:315 arg1 transferase 279:289 Human O-GlcNAc transferase 264:289 Human O-GlcNAc transferase (OGT) 264:295 Human O-GlcNAc transferase (OGT) is an intracellular enzyme responsible for O-linked N-acetylglucosamine (O-GlcNAc) glycosylation, and the deregulation of OGT activity occurs in cancer, diabetes, and neurodegenerative disease. 29115822 2 20 theme activity 423:430 arg1 deregulation 403:414 the deregulation 399:414 the deregulation of OGT activity 399:430 Human O-GlcNAc transferase (OGT) is an intracellular enzyme responsible for O-linked N-acetylglucosamine (O-GlcNAc) glycosylation, and the deregulation of OGT activity occurs in cancer, diabetes, and neurodegenerative disease. 29115822 5 21 theme OGT 873:875 arg1 presence 861:868 the presence 857:868 the presence of OGT 857:875 In the presence of OGT, it catalyzes the glycosylation reaction to generate a glycosylated peptide that is a protease-protection peptide. 29115822 6 22 theme glycosylated 1006:1017 arg1 peptides 1039:1046 The resultant glycosylated Cy5/biotin-modified peptides 992:1046 The resultant glycosylated Cy5/biotin-modified peptides 992:1046 The resultant glycosylated Cy5/biotin-modified peptides may assemble on the surface of the streptavidin-coated QD to obtain a QD-peptide-Cy5 nanostructure in which the fluorescence resonance energy transfer (FRET) from the QD to Cy5 can occur, leading to the emission of Cy5 which can be quantified by single-molecule detection. 29115822 6 23 theme resonance 1173:1181 arg1 FRET 1200:1203 FRET 1200:1203 FRET 1200:1203 The resultant glycosylated Cy5/biotin-modified peptides may assemble on the surface of the streptavidin-coated QD to obtain a QD-peptide-Cy5 nanostructure in which the fluorescence resonance energy transfer (FRET) from the QD to Cy5 can occur, leading to the emission of Cy5 which can be quantified by single-molecule detection. 29115822 6 23 theme resonance 1173:1181 arg1 transfer 1190:1197 the fluorescence resonance energy transfer 1156:1197 the fluorescence resonance energy transfer (FRET) from the QD to Cy5 1156:1223 The resultant glycosylated Cy5/biotin-modified peptides may assemble on the surface of the streptavidin-coated QD to obtain a QD-peptide-Cy5 nanostructure in which the fluorescence resonance energy transfer (FRET) from the QD to Cy5 can occur, leading to the emission of Cy5 which can be quantified by single-molecule detection. 29115822 3 24 theme sensitive 554:562 arg1 assay 568:572 sensitive OGT assay 554:572 sensitive OGT assay 554:572 Here we develop a single quantum dot (QD)-based nanosensor for sensitive OGT assay. 29115822 1 25 theme biological 203:212 arg1 events 226:231 biological recognition events 203:231 biological recognition events in development and physiology 203:261 Protein glycosylation is a ubiquitous post-translational modification that plays crucial roles in modulating biological recognition events in development and physiology. 29115822 0 26 theme Quantum 7:13 arg1 Nanosensor 25:34 Single Quantum Dot-Based Nanosensor 0:34 Single Quantum Dot-Based Nanosensor for Sensitive Detection of O-GlcNAc Transferase Activity. 0:92 Single Quantum Dot-Based Nanosensor for Sensitive Detection of O-GlcNAc Transferase Activity. 29115822 8 27 used used 1638:1641 arg2 method 1624:1629 this method 1619:1629 this method 1619:1629 Moreover, this method can be used for enzyme kinetic analysis, quantitative detection of cellular OGT activity, and the screening of OGT inhibitors, holding great potential for further application in drug discovery and clinical diagnosis. 29115822 8 28 theme activity 1711:1718 arg1 screening 1729:1737 the screening 1725:1737 the screening of OGT inhibitors, holding great potential for further application in drug discovery and clinical diagnosis 1725:1845 Moreover, this method can be used for enzyme kinetic analysis, quantitative detection of cellular OGT activity, and the screening of OGT inhibitors, holding great potential for further application in drug discovery and clinical diagnosis. 29115822 8 28 theme activity 1711:1718 arg1 analysis 1662:1669 enzyme kinetic analysis 1647:1669 enzyme kinetic analysis 1647:1669 Moreover, this method can be used for enzyme kinetic analysis, quantitative detection of cellular OGT activity, and the screening of OGT inhibitors, holding great potential for further application in drug discovery and clinical diagnosis. 29115822 8 28 theme activity 1711:1718 arg1 detection 1685:1693 quantitative detection 1672:1693 quantitative detection of cellular OGT activity 1672:1718 Moreover, this method can be used for enzyme kinetic analysis, quantitative detection of cellular OGT activity, and the screening of OGT inhibitors, holding great potential for further application in drug discovery and clinical diagnosis. 29115822 1 29 theme Protein 94:100 arg1 modification 151:162 a ubiquitous post-translational modification 119:162 a ubiquitous post-translational modification that plays crucial roles in modulating biological recognition events in development and physiology 119:261 Protein glycosylation is a ubiquitous post-translational modification that plays crucial roles in modulating biological recognition events in development and physiology. 29115822 1 29 theme Protein 94:100 arg1 glycosylation 102:114 Protein glycosylation 94:114 Protein glycosylation 94:114 Protein glycosylation is a ubiquitous post-translational modification that plays crucial roles in modulating biological recognition events in development and physiology. 29115822 1 30 theme recognition 214:224 arg1 events 226:231 biological recognition events 203:231 biological recognition events in development and physiology 203:261 Protein glycosylation is a ubiquitous post-translational modification that plays crucial roles in modulating biological recognition events in development and physiology. 29115822 0 31 theme Single 0:5 arg1 Nanosensor 25:34 Single Quantum Dot-Based Nanosensor 0:34 Single Quantum Dot-Based Nanosensor for Sensitive Detection of O-GlcNAc Transferase Activity. 0:92 Single Quantum Dot-Based Nanosensor for Sensitive Detection of O-GlcNAc Transferase Activity. 29115822 6 32 theme resultant 996:1004 arg1 peptides 1039:1046 The resultant glycosylated Cy5/biotin-modified peptides 992:1046 The resultant glycosylated Cy5/biotin-modified peptides 992:1046 The resultant glycosylated Cy5/biotin-modified peptides may assemble on the surface of the streptavidin-coated QD to obtain a QD-peptide-Cy5 nanostructure in which the fluorescence resonance energy transfer (FRET) from the QD to Cy5 can occur, leading to the emission of Cy5 which can be quantified by single-molecule detection. 29115822 6 33 theme Cy5 1263:1265 arg1 emission 1251:1258 the emission 1247:1258 the emission of Cy5 which can be quantified by single-molecule detection 1247:1318 The resultant glycosylated Cy5/biotin-modified peptides may assemble on the surface of the streptavidin-coated QD to obtain a QD-peptide-Cy5 nanostructure in which the fluorescence resonance energy transfer (FRET) from the QD to Cy5 can occur, leading to the emission of Cy5 which can be quantified by single-molecule detection. 29115822 2 34 theme N-acetylglucosamine 349:367 arg1 glycosylation 380:392 O-linked N-acetylglucosamine (O-GlcNAc) glycosylation 340:392 O-linked N-acetylglucosamine (O-GlcNAc) glycosylation 340:392 Human O-GlcNAc transferase (OGT) is an intracellular enzyme responsible for O-linked N-acetylglucosamine (O-GlcNAc) glycosylation, and the deregulation of OGT activity occurs in cancer, diabetes, and neurodegenerative disease. 29115822 2 35 theme OGT 419:421 arg1 activity 423:430 OGT activity 419:430 OGT activity 419:430 Human O-GlcNAc transferase (OGT) is an intracellular enzyme responsible for O-linked N-acetylglucosamine (O-GlcNAc) glycosylation, and the deregulation of OGT activity occurs in cancer, diabetes, and neurodegenerative disease. 29115822 2 36 theme neurodegenerative 464:480 arg1 disease 482:488 neurodegenerative disease 464:488 neurodegenerative disease 464:488 Human O-GlcNAc transferase (OGT) is an intracellular enzyme responsible for O-linked N-acetylglucosamine (O-GlcNAc) glycosylation, and the deregulation of OGT activity occurs in cancer, diabetes, and neurodegenerative disease. 29115822 2 37 theme O-linked 340:347 arg1 O-GlcNAc 370:377 O-GlcNAc 370:377 O-GlcNAc 370:377 Human O-GlcNAc transferase (OGT) is an intracellular enzyme responsible for O-linked N-acetylglucosamine (O-GlcNAc) glycosylation, and the deregulation of OGT activity occurs in cancer, diabetes, and neurodegenerative disease. 29115822 2 37 theme O-linked 340:347 arg1 N-acetylglucosamine 349:367 O-linked N-acetylglucosamine 340:367 O-linked N-acetylglucosamine (O-GlcNAc) glycosylation 340:392 Human O-GlcNAc transferase (OGT) is an intracellular enzyme responsible for O-linked N-acetylglucosamine (O-GlcNAc) glycosylation, and the deregulation of OGT activity occurs in cancer, diabetes, and neurodegenerative disease. 29115822 6 38 theme QD 1103:1104 arg1 surface 1068:1074 the surface 1064:1074 the surface of the streptavidin-coated QD 1064:1104 The resultant glycosylated Cy5/biotin-modified peptides may assemble on the surface of the streptavidin-coated QD to obtain a QD-peptide-Cy5 nanostructure in which the fluorescence resonance energy transfer (FRET) from the QD to Cy5 can occur, leading to the emission of Cy5 which can be quantified by single-molecule detection. 29115822 0 39 theme Dot-Based 15:23 arg1 Nanosensor 25:34 Single Quantum Dot-Based Nanosensor 0:34 Single Quantum Dot-Based Nanosensor for Sensitive Detection of O-GlcNAc Transferase Activity. 0:92 Single Quantum Dot-Based Nanosensor for Sensitive Detection of O-GlcNAc Transferase Activity. 29115822 5 40 theme glycosylated 932:943 arg1 peptide 983:989 a protease-protection peptide 961:989 a protease-protection peptide 961:989 In the presence of OGT, it catalyzes the glycosylation reaction to generate a glycosylated peptide that is a protease-protection peptide. 29115822 5 40 theme glycosylated 932:943 arg1 peptide 945:951 a glycosylated peptide 930:951 a glycosylated peptide that is a protease-protection peptide 930:989 In the presence of OGT, it catalyzes the glycosylation reaction to generate a glycosylated peptide that is a protease-protection peptide. 29115822 7 41 theme fluorescent 1575:1585 arg1 analogues 1598:1606 fluorescent UDP-GlcNAc analogues 1575:1606 fluorescent UDP-GlcNAc analogues 1575:1606 This method exhibits high sensitivity with a limit of detection of 3.47 × 10-13 M, and it is very simple and straightforward without the involvement of any enzyme purification, radioisotope-labeled sugar donors, specific antibodies, and the synthesis of fluorescent UDP-GlcNAc analogues. 29115822 4 42 theme nonradioactive 757:770 arg1 UDP-GlcNAc 772:781 a universal nonradioactive UDP-GlcNAc 745:781 a universal nonradioactive UDP-GlcNAc as the sugar donor 745:800 We design a Cy5/biotin-modified peptide with a serine hydroxyl group for sensing OGT and a protease site adjacent to the glycosylation site for proteinase cleavage, with a universal nonradioactive UDP-GlcNAc as the sugar donor and a Cy5/biotin-modified peptide as the substrate. 29115822 8 43 theme inhibitors 1746:1755 arg1 screening 1729:1737 the screening 1725:1737 the screening of OGT inhibitors, holding great potential for further application in drug discovery and clinical diagnosis 1725:1845 Moreover, this method can be used for enzyme kinetic analysis, quantitative detection of cellular OGT activity, and the screening of OGT inhibitors, holding great potential for further application in drug discovery and clinical diagnosis. 29115822 8 43 theme inhibitors 1746:1755 arg1 analysis 1662:1669 enzyme kinetic analysis 1647:1669 enzyme kinetic analysis 1647:1669 Moreover, this method can be used for enzyme kinetic analysis, quantitative detection of cellular OGT activity, and the screening of OGT inhibitors, holding great potential for further application in drug discovery and clinical diagnosis. 29115822 8 43 theme inhibitors 1746:1755 arg1 detection 1685:1693 quantitative detection 1672:1693 quantitative detection of cellular OGT activity 1672:1718 Moreover, this method can be used for enzyme kinetic analysis, quantitative detection of cellular OGT activity, and the screening of OGT inhibitors, holding great potential for further application in drug discovery and clinical diagnosis. 29115822 4 44 theme glycosylation 696:708 arg1 site 710:713 the glycosylation site 692:713 the glycosylation site for proteinase cleavage 692:737 We design a Cy5/biotin-modified peptide with a serine hydroxyl group for sensing OGT and a protease site adjacent to the glycosylation site for proteinase cleavage, with a universal nonradioactive UDP-GlcNAc as the sugar donor and a Cy5/biotin-modified peptide as the substrate. 29115822 0 45 theme Sensitive 40:48 arg1 Detection 50:58 Sensitive Detection 40:58 Sensitive Detection of O-GlcNAc Transferase Activity 40:91 Single Quantum Dot-Based Nanosensor for Sensitive Detection of O-GlcNAc Transferase Activity. 29115822 4 46 theme proteinase 719:728 arg1 cleavage 730:737 proteinase cleavage 719:737 proteinase cleavage 719:737 We design a Cy5/biotin-modified peptide with a serine hydroxyl group for sensing OGT and a protease site adjacent to the glycosylation site for proteinase cleavage, with a universal nonradioactive UDP-GlcNAc as the sugar donor and a Cy5/biotin-modified peptide as the substrate. 29115822 8 47 theme cellular 1698:1705 arg1 activity 1711:1718 cellular OGT activity 1698:1718 cellular OGT activity 1698:1718 Moreover, this method can be used for enzyme kinetic analysis, quantitative detection of cellular OGT activity, and the screening of OGT inhibitors, holding great potential for further application in drug discovery and clinical diagnosis. 29115822 4 48 theme adjacent 680:687 arg1 site 675:678 a protease site 664:678 a protease site adjacent to the glycosylation site for proteinase cleavage 664:737 We design a Cy5/biotin-modified peptide with a serine hydroxyl group for sensing OGT and a protease site adjacent to the glycosylation site for proteinase cleavage, with a universal nonradioactive UDP-GlcNAc as the sugar donor and a Cy5/biotin-modified peptide as the substrate. 29115822 6 49 theme QD-peptide-Cy5 1118:1131 arg1 nanostructure 1133:1145 a QD-peptide-Cy5 nanostructure 1116:1145 a QD-peptide-Cy5 nanostructure in which the fluorescence resonance energy transfer (FRET) from the QD to Cy5 can occur, leading to the emission of Cy5 which can be quantified by single-molecule detection 1116:1318 The resultant glycosylated Cy5/biotin-modified peptides may assemble on the surface of the streptavidin-coated QD to obtain a QD-peptide-Cy5 nanostructure in which the fluorescence resonance energy transfer (FRET) from the QD to Cy5 can occur, leading to the emission of Cy5 which can be quantified by single-molecule detection. 29115822 2 50 link O-linked 340:347 arg1 O-GlcNAc 370:377 O-GlcNAc 370:377 O-GlcNAc 370:377 Human O-GlcNAc transferase (OGT) is an intracellular enzyme responsible for O-linked N-acetylglucosamine (O-GlcNAc) glycosylation, and the deregulation of OGT activity occurs in cancer, diabetes, and neurodegenerative disease. 29115822 2 50 link O-linked 340:347 arg1 N-acetylglucosamine 349:367 O-linked N-acetylglucosamine 340:367 O-linked N-acetylglucosamine (O-GlcNAc) glycosylation 340:392 Human O-GlcNAc transferase (OGT) is an intracellular enzyme responsible for O-linked N-acetylglucosamine (O-GlcNAc) glycosylation, and the deregulation of OGT activity occurs in cancer, diabetes, and neurodegenerative disease. 29115822 5 51 gly glycosylated 932:943 arg1 peptide 983:989 a protease-protection peptide 961:989 a protease-protection peptide 961:989 In the presence of OGT, it catalyzes the glycosylation reaction to generate a glycosylated peptide that is a protease-protection peptide. 29115822 5 51 gly glycosylated 932:943 arg1 peptide 945:951 a glycosylated peptide 930:951 a glycosylated peptide that is a protease-protection peptide 930:989 In the presence of OGT, it catalyzes the glycosylation reaction to generate a glycosylated peptide that is a protease-protection peptide. 29115822 7 52 theme specific 1533:1540 arg1 antibodies 1542:1551 specific antibodies 1533:1551 specific antibodies 1533:1551 This method exhibits high sensitivity with a limit of detection of 3.47 × 10-13 M, and it is very simple and straightforward without the involvement of any enzyme purification, radioisotope-labeled sugar donors, specific antibodies, and the synthesis of fluorescent UDP-GlcNAc analogues. 29115822 2 53 theme O-GlcNAc 270:277 arg1 enzyme 317:322 an intracellular enzyme 300:322 an intracellular enzyme responsible for O-linked N-acetylglucosamine (O-GlcNAc) glycosylation 300:392 Human O-GlcNAc transferase (OGT) is an intracellular enzyme responsible for O-linked N-acetylglucosamine (O-GlcNAc) glycosylation, and the deregulation of OGT activity occurs in cancer, diabetes, and neurodegenerative disease. 29115822 2 53 theme O-GlcNAc 270:277 arg1 OGT 292:294 OGT 292:294 OGT 292:294 Human O-GlcNAc transferase (OGT) is an intracellular enzyme responsible for O-linked N-acetylglucosamine (O-GlcNAc) glycosylation, and the deregulation of OGT activity occurs in cancer, diabetes, and neurodegenerative disease. 29115822 2 53 theme O-GlcNAc 270:277 arg1 transferase 279:289 Human O-GlcNAc transferase 264:289 Human O-GlcNAc transferase (OGT) 264:295 Human O-GlcNAc transferase (OGT) is an intracellular enzyme responsible for O-linked N-acetylglucosamine (O-GlcNAc) glycosylation, and the deregulation of OGT activity occurs in cancer, diabetes, and neurodegenerative disease. 29115822 8 54 theme OGT 1742:1744 arg1 inhibitors 1746:1755 OGT inhibitors 1742:1755 OGT inhibitors 1742:1755 Moreover, this method can be used for enzyme kinetic analysis, quantitative detection of cellular OGT activity, and the screening of OGT inhibitors, holding great potential for further application in drug discovery and clinical diagnosis. 29115822 2 55 theme Human 264:268 arg1 enzyme 317:322 an intracellular enzyme 300:322 an intracellular enzyme responsible for O-linked N-acetylglucosamine (O-GlcNAc) glycosylation 300:392 Human O-GlcNAc transferase (OGT) is an intracellular enzyme responsible for O-linked N-acetylglucosamine (O-GlcNAc) glycosylation, and the deregulation of OGT activity occurs in cancer, diabetes, and neurodegenerative disease. 29115822 2 55 theme Human 264:268 arg1 OGT 292:294 OGT 292:294 OGT 292:294 Human O-GlcNAc transferase (OGT) is an intracellular enzyme responsible for O-linked N-acetylglucosamine (O-GlcNAc) glycosylation, and the deregulation of OGT activity occurs in cancer, diabetes, and neurodegenerative disease. 29115822 2 55 theme Human 264:268 arg1 transferase 279:289 Human O-GlcNAc transferase 264:289 Human O-GlcNAc transferase (OGT) 264:295 Human O-GlcNAc transferase (OGT) is an intracellular enzyme responsible for O-linked N-acetylglucosamine (O-GlcNAc) glycosylation, and the deregulation of OGT activity occurs in cancer, diabetes, and neurodegenerative disease. 29115822 1 56 theme ubiquitous 121:130 arg1 modification 151:162 a ubiquitous post-translational modification 119:162 a ubiquitous post-translational modification that plays crucial roles in modulating biological recognition events in development and physiology 119:261 Protein glycosylation is a ubiquitous post-translational modification that plays crucial roles in modulating biological recognition events in development and physiology. 29115822 1 56 theme ubiquitous 121:130 arg1 glycosylation 102:114 Protein glycosylation 94:114 Protein glycosylation 94:114 Protein glycosylation is a ubiquitous post-translational modification that plays crucial roles in modulating biological recognition events in development and physiology. 29115822 4 57 gly glycosylation 696:708 arg2 site 710:713 the glycosylation site 692:713 the glycosylation site for proteinase cleavage 692:737 We design a Cy5/biotin-modified peptide with a serine hydroxyl group for sensing OGT and a protease site adjacent to the glycosylation site for proteinase cleavage, with a universal nonradioactive UDP-GlcNAc as the sugar donor and a Cy5/biotin-modified peptide as the substrate. 29115822 6 58 gly glycosylated 1006:1017 arg1 peptides 1039:1046 The resultant glycosylated Cy5/biotin-modified peptides 992:1046 The resultant glycosylated Cy5/biotin-modified peptides 992:1046 The resultant glycosylated Cy5/biotin-modified peptides may assemble on the surface of the streptavidin-coated QD to obtain a QD-peptide-Cy5 nanostructure in which the fluorescence resonance energy transfer (FRET) from the QD to Cy5 can occur, leading to the emission of Cy5 which can be quantified by single-molecule detection. 29115822 1 59 theme post-translational 132:149 arg1 modification 151:162 a ubiquitous post-translational modification 119:162 a ubiquitous post-translational modification that plays crucial roles in modulating biological recognition events in development and physiology 119:261 Protein glycosylation is a ubiquitous post-translational modification that plays crucial roles in modulating biological recognition events in development and physiology. 29115822 1 59 theme post-translational 132:149 arg1 glycosylation 102:114 Protein glycosylation 94:114 Protein glycosylation 94:114 Protein glycosylation is a ubiquitous post-translational modification that plays crucial roles in modulating biological recognition events in development and physiology. 29115822 7 60 theme detection 1375:1383 arg1 limit 1366:1370 a limit 1364:1370 a limit of detection of 3.47 × 10-13 M 1364:1401 This method exhibits high sensitivity with a limit of detection of 3.47 × 10-13 M, and it is very simple and straightforward without the involvement of any enzyme purification, radioisotope-labeled sugar donors, specific antibodies, and the synthesis of fluorescent UDP-GlcNAc analogues. 29115822 7 61 theme M 1401:1401 arg1 detection 1375:1383 detection 1375:1383 detection of 3.47 × 10-13 M 1375:1401 This method exhibits high sensitivity with a limit of detection of 3.47 × 10-13 M, and it is very simple and straightforward without the involvement of any enzyme purification, radioisotope-labeled sugar donors, specific antibodies, and the synthesis of fluorescent UDP-GlcNAc analogues. 29115822 3 62 theme single 509:514 arg1 nanosensor 539:548 a single quantum dot (QD)-based nanosensor 507:548 a single quantum dot (QD)-based nanosensor for sensitive OGT assay 507:572 Here we develop a single quantum dot (QD)-based nanosensor for sensitive OGT assay. 29115822 8 63 theme kinetic 1654:1660 arg1 analysis 1662:1669 enzyme kinetic analysis 1647:1669 enzyme kinetic analysis 1647:1669 Moreover, this method can be used for enzyme kinetic analysis, quantitative detection of cellular OGT activity, and the screening of OGT inhibitors, holding great potential for further application in drug discovery and clinical diagnosis. 29115822 4 64 theme hydroxyl 629:636 arg1 group 638:642 a serine hydroxyl group 620:642 a serine hydroxyl group 620:642 We design a Cy5/biotin-modified peptide with a serine hydroxyl group for sensing OGT and a protease site adjacent to the glycosylation site for proteinase cleavage, with a universal nonradioactive UDP-GlcNAc as the sugar donor and a Cy5/biotin-modified peptide as the substrate. 29115822 4 65 theme sugar 790:794 arg1 donor 796:800 the sugar donor 786:800 the sugar donor 786:800 We design a Cy5/biotin-modified peptide with a serine hydroxyl group for sensing OGT and a protease site adjacent to the glycosylation site for proteinase cleavage, with a universal nonradioactive UDP-GlcNAc as the sugar donor and a Cy5/biotin-modified peptide as the substrate. 29115822 7 66 theme radioisotope-labeled 1498:1517 arg1 donors 1525:1530 radioisotope-labeled sugar donors 1498:1530 radioisotope-labeled sugar donors 1498:1530 This method exhibits high sensitivity with a limit of detection of 3.47 × 10-13 M, and it is very simple and straightforward without the involvement of any enzyme purification, radioisotope-labeled sugar donors, specific antibodies, and the synthesis of fluorescent UDP-GlcNAc analogues. 29115822 3 67 theme OGT 564:566 arg1 assay 568:572 sensitive OGT assay 554:572 sensitive OGT assay 554:572 Here we develop a single quantum dot (QD)-based nanosensor for sensitive OGT assay. 29115822 8 68 theme further 1786:1792 arg1 application 1794:1804 further application 1786:1804 further application in drug discovery and clinical diagnosis 1786:1845 Moreover, this method can be used for enzyme kinetic analysis, quantitative detection of cellular OGT activity, and the screening of OGT inhibitors, holding great potential for further application in drug discovery and clinical diagnosis. 29115822 5 69 theme glycosylation 895:907 arg1 reaction 909:916 the glycosylation reaction 891:916 the glycosylation reaction 891:916 In the presence of OGT, it catalyzes the glycosylation reaction to generate a glycosylated peptide that is a protease-protection peptide. 29115822 7 70 theme high 1342:1345 arg1 sensitivity 1347:1357 high sensitivity 1342:1357 high sensitivity 1342:1357 This method exhibits high sensitivity with a limit of detection of 3.47 × 10-13 M, and it is very simple and straightforward without the involvement of any enzyme purification, radioisotope-labeled sugar donors, specific antibodies, and the synthesis of fluorescent UDP-GlcNAc analogues. 29115822 4 71 theme serine 622:627 arg1 group 638:642 a serine hydroxyl group 620:642 a serine hydroxyl group 620:642 We design a Cy5/biotin-modified peptide with a serine hydroxyl group for sensing OGT and a protease site adjacent to the glycosylation site for proteinase cleavage, with a universal nonradioactive UDP-GlcNAc as the sugar donor and a Cy5/biotin-modified peptide as the substrate. 29115822 0 72 theme Transferase 72:82 arg1 Activity 84:91 O-GlcNAc Transferase Activity 63:91 O-GlcNAc Transferase Activity 63:91 Single Quantum Dot-Based Nanosensor for Sensitive Detection of O-GlcNAc Transferase Activity. 29115822 7 73 theme sugar 1519:1523 arg1 donors 1525:1530 radioisotope-labeled sugar donors 1498:1530 radioisotope-labeled sugar donors 1498:1530 This method exhibits high sensitivity with a limit of detection of 3.47 × 10-13 M, and it is very simple and straightforward without the involvement of any enzyme purification, radioisotope-labeled sugar donors, specific antibodies, and the synthesis of fluorescent UDP-GlcNAc analogues. 29115822 4 74 with peptide 607:613 arg1 group 638:642 a serine hydroxyl group 620:642 a serine hydroxyl group 620:642 We design a Cy5/biotin-modified peptide with a serine hydroxyl group for sensing OGT and a protease site adjacent to the glycosylation site for proteinase cleavage, with a universal nonradioactive UDP-GlcNAc as the sugar donor and a Cy5/biotin-modified peptide as the substrate. 29115822 1 75 from events 226:231 arg1 development 236:246 development 236:246 development 236:246 Protein glycosylation is a ubiquitous post-translational modification that plays crucial roles in modulating biological recognition events in development and physiology. 29115822 1 75 from events 226:231 arg1 physiology 252:261 physiology 252:261 physiology 252:261 Protein glycosylation is a ubiquitous post-translational modification that plays crucial roles in modulating biological recognition events in development and physiology. 29115822 3 76 theme -based 532:537 arg1 nanosensor 539:548 a single quantum dot (QD)-based nanosensor 507:548 a single quantum dot (QD)-based nanosensor for sensitive OGT assay 507:572 Here we develop a single quantum dot (QD)-based nanosensor for sensitive OGT assay. 29115822 4 77 theme protease 666:673 arg1 site 675:678 a protease site 664:678 a protease site adjacent to the glycosylation site for proteinase cleavage 664:737 We design a Cy5/biotin-modified peptide with a serine hydroxyl group for sensing OGT and a protease site adjacent to the glycosylation site for proteinase cleavage, with a universal nonradioactive UDP-GlcNAc as the sugar donor and a Cy5/biotin-modified peptide as the substrate. 29115822 7 78 theme UDP-GlcNAc 1587:1596 arg1 analogues 1598:1606 fluorescent UDP-GlcNAc analogues 1575:1606 fluorescent UDP-GlcNAc analogues 1575:1606 This method exhibits high sensitivity with a limit of detection of 3.47 × 10-13 M, and it is very simple and straightforward without the involvement of any enzyme purification, radioisotope-labeled sugar donors, specific antibodies, and the synthesis of fluorescent UDP-GlcNAc analogues. 29115822 0 79 theme O-GlcNAc 63:70 arg1 Activity 84:91 O-GlcNAc Transferase Activity 63:91 O-GlcNAc Transferase Activity 63:91 Single Quantum Dot-Based Nanosensor for Sensitive Detection of O-GlcNAc Transferase Activity. 29115822 7 80 theme purification 1484:1495 arg1 involvement 1458:1468 the involvement 1454:1468 the involvement of any enzyme purification 1454:1495 This method exhibits high sensitivity with a limit of detection of 3.47 × 10-13 M, and it is very simple and straightforward without the involvement of any enzyme purification, radioisotope-labeled sugar donors, specific antibodies, and the synthesis of fluorescent UDP-GlcNAc analogues. 29115822 7 80 theme purification 1484:1495 arg1 antibodies 1542:1551 specific antibodies 1533:1551 specific antibodies 1533:1551 This method exhibits high sensitivity with a limit of detection of 3.47 × 10-13 M, and it is very simple and straightforward without the involvement of any enzyme purification, radioisotope-labeled sugar donors, specific antibodies, and the synthesis of fluorescent UDP-GlcNAc analogues. 29115822 7 80 theme purification 1484:1495 arg1 donors 1525:1530 radioisotope-labeled sugar donors 1498:1530 radioisotope-labeled sugar donors 1498:1530 This method exhibits high sensitivity with a limit of detection of 3.47 × 10-13 M, and it is very simple and straightforward without the involvement of any enzyme purification, radioisotope-labeled sugar donors, specific antibodies, and the synthesis of fluorescent UDP-GlcNAc analogues. 29115822 7 80 theme purification 1484:1495 arg1 synthesis 1562:1570 the synthesis 1558:1570 the synthesis of fluorescent UDP-GlcNAc analogues 1558:1606 This method exhibits high sensitivity with a limit of detection of 3.47 × 10-13 M, and it is very simple and straightforward without the involvement of any enzyme purification, radioisotope-labeled sugar donors, specific antibodies, and the synthesis of fluorescent UDP-GlcNAc analogues. 29115822 4 81 theme Cy5/biotin-modified 808:826 arg1 peptide 828:834 a Cy5/biotin-modified peptide 806:834 a Cy5/biotin-modified peptide as the substrate 806:851 We design a Cy5/biotin-modified peptide with a serine hydroxyl group for sensing OGT and a protease site adjacent to the glycosylation site for proteinase cleavage, with a universal nonradioactive UDP-GlcNAc as the sugar donor and a Cy5/biotin-modified peptide as the substrate. 29115822 1 82 theme crucial 175:181 arg1 roles 183:187 crucial roles 175:187 crucial roles 175:187 Protein glycosylation is a ubiquitous post-translational modification that plays crucial roles in modulating biological recognition events in development and physiology. 29115822 8 83 theme enzyme 1647:1652 arg1 analysis 1662:1669 enzyme kinetic analysis 1647:1669 enzyme kinetic analysis 1647:1669 Moreover, this method can be used for enzyme kinetic analysis, quantitative detection of cellular OGT activity, and the screening of OGT inhibitors, holding great potential for further application in drug discovery and clinical diagnosis. 29115822 7 84 theme analogues 1598:1606 arg1 involvement 1458:1468 the involvement 1454:1468 the involvement of any enzyme purification 1454:1495 This method exhibits high sensitivity with a limit of detection of 3.47 × 10-13 M, and it is very simple and straightforward without the involvement of any enzyme purification, radioisotope-labeled sugar donors, specific antibodies, and the synthesis of fluorescent UDP-GlcNAc analogues. 29115822 7 84 theme analogues 1598:1606 arg1 antibodies 1542:1551 specific antibodies 1533:1551 specific antibodies 1533:1551 This method exhibits high sensitivity with a limit of detection of 3.47 × 10-13 M, and it is very simple and straightforward without the involvement of any enzyme purification, radioisotope-labeled sugar donors, specific antibodies, and the synthesis of fluorescent UDP-GlcNAc analogues. 29115822 7 84 theme analogues 1598:1606 arg1 donors 1525:1530 radioisotope-labeled sugar donors 1498:1530 radioisotope-labeled sugar donors 1498:1530 This method exhibits high sensitivity with a limit of detection of 3.47 × 10-13 M, and it is very simple and straightforward without the involvement of any enzyme purification, radioisotope-labeled sugar donors, specific antibodies, and the synthesis of fluorescent UDP-GlcNAc analogues. 29115822 7 84 theme analogues 1598:1606 arg1 synthesis 1562:1570 the synthesis 1558:1570 the synthesis of fluorescent UDP-GlcNAc analogues 1558:1606 This method exhibits high sensitivity with a limit of detection of 3.47 × 10-13 M, and it is very simple and straightforward without the involvement of any enzyme purification, radioisotope-labeled sugar donors, specific antibodies, and the synthesis of fluorescent UDP-GlcNAc analogues. 28062629 1 0 used used 316:319 arg2 counterpart 278:288 its physiologically active counterpart 251:288 its physiologically active counterpart 251:288 BACKGROUND: Currently, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and its physiologically active counterpart, BNP, are most frequently used as biomarkers for diagnosis, prognosis, and disease monitoring of heart failure (HF). 28062629 1 0 used used 316:319 arg2 peptide 227:233 N-terminal pro-B-type natriuretic peptide 193:233 N-terminal pro-B-type natriuretic peptide (NT-proBNP) 193:245 BACKGROUND: Currently, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and its physiologically active counterpart, BNP, are most frequently used as biomarkers for diagnosis, prognosis, and disease monitoring of heart failure (HF). 28062629 1 0 used used 316:319 arg2 NT-proBNP 236:244 NT-proBNP 236:244 NT-proBNP 236:244 BACKGROUND: Currently, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and its physiologically active counterpart, BNP, are most frequently used as biomarkers for diagnosis, prognosis, and disease monitoring of heart failure (HF). 28062629 1 0 used used 316:319 arg2 BNP 291:293 BNP 291:293 BNP 291:293 BACKGROUND: Currently, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and its physiologically active counterpart, BNP, are most frequently used as biomarkers for diagnosis, prognosis, and disease monitoring of heart failure (HF). 28062629 1 0 used used 316:319 arg2 biomarkers 324:333 biomarkers 324:333 biomarkers for diagnosis, prognosis, and disease monitoring of heart failure (HF) 324:404 BACKGROUND: Currently, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and its physiologically active counterpart, BNP, are most frequently used as biomarkers for diagnosis, prognosis, and disease monitoring of heart failure (HF). 28062629 1 1 theme disease 365:371 arg1 monitoring 373:382 disease monitoring 365:382 disease monitoring 365:382 BACKGROUND: Currently, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and its physiologically active counterpart, BNP, are most frequently used as biomarkers for diagnosis, prognosis, and disease monitoring of heart failure (HF). 28062629 10 2 theme specific 1946:1953 arg1 antibodies 1935:1944 antibodies 1935:1944 antibodies specific for the central region of (NT-) proBNP, which detect mostly nonglycosylated forms 1935:2035 This information may also have an impact on commercial immunoassays applying antibodies specific for the central region of (NT-) proBNP, which detect mostly nonglycosylated forms. 28062629 1 3 theme failure 393:399 arg1 diagnosis 339:347 diagnosis 339:347 diagnosis 339:347 BACKGROUND: Currently, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and its physiologically active counterpart, BNP, are most frequently used as biomarkers for diagnosis, prognosis, and disease monitoring of heart failure (HF). 28062629 1 3 theme failure 393:399 arg1 monitoring 373:382 disease monitoring 365:382 disease monitoring 365:382 BACKGROUND: Currently, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and its physiologically active counterpart, BNP, are most frequently used as biomarkers for diagnosis, prognosis, and disease monitoring of heart failure (HF). 28062629 1 3 theme failure 393:399 arg1 prognosis 350:358 prognosis 350:358 prognosis 350:358 BACKGROUND: Currently, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and its physiologically active counterpart, BNP, are most frequently used as biomarkers for diagnosis, prognosis, and disease monitoring of heart failure (HF). 28062629 5 4 gly glycosylation 872:884 arg2 sites 886:890 The glycosylation sites 868:890 The glycosylation sites of (NT-) proBNP (NT-proBNP and/or proBNP) 868:932 METHODS: The glycosylation sites of (NT-) proBNP (NT-proBNP and/or proBNP) were characterized in leftovers of heparinized plasma samples of severe HF patients (NT-proBNP: >10000 ng/L) by using tandem immunoaffinity purification, sequential exoglycosidase treatment for glycan trimming, β-elimination and Michael addition chemistry, as well as high-resolution nano-flow liquid chromatography electrospray multistage mass spectrometry. 28062629 5 4 gly glycosylation 872:884 arg2 proBNP 901:906 (NT-) proBNP 895:906 (NT-) proBNP (NT-proBNP and/or proBNP) 895:932 METHODS: The glycosylation sites of (NT-) proBNP (NT-proBNP and/or proBNP) were characterized in leftovers of heparinized plasma samples of severe HF patients (NT-proBNP: >10000 ng/L) by using tandem immunoaffinity purification, sequential exoglycosidase treatment for glycan trimming, β-elimination and Michael addition chemistry, as well as high-resolution nano-flow liquid chromatography electrospray multistage mass spectrometry. 28062629 5 4 gly glycosylation 872:884 arg1 proBNP 901:906 (NT-) proBNP 895:906 (NT-) proBNP (NT-proBNP and/or proBNP) 895:932 METHODS: The glycosylation sites of (NT-) proBNP (NT-proBNP and/or proBNP) were characterized in leftovers of heparinized plasma samples of severe HF patients (NT-proBNP: >10000 ng/L) by using tandem immunoaffinity purification, sequential exoglycosidase treatment for glycan trimming, β-elimination and Michael addition chemistry, as well as high-resolution nano-flow liquid chromatography electrospray multistage mass spectrometry. 28062629 7 5 theme accurate 1456:1463 arg1 determination 1470:1482 highly accurate mass determination 1449:1482 highly accurate mass determination 1449:1482 Differentially glycosylated variants were detected based on highly accurate mass determination and multistage mass spectrometry. 28062629 5 6 theme high-resolution 1202:1216 arg1 spectrometry 1279:1290 high-resolution nano-flow liquid chromatography electrospray multistage mass spectrometry 1202:1290 high-resolution nano-flow liquid chromatography electrospray multistage mass spectrometry 1202:1290 METHODS: The glycosylation sites of (NT-) proBNP (NT-proBNP and/or proBNP) were characterized in leftovers of heparinized plasma samples of severe HF patients (NT-proBNP: >10000 ng/L) by using tandem immunoaffinity purification, sequential exoglycosidase treatment for glycan trimming, β-elimination and Michael addition chemistry, as well as high-resolution nano-flow liquid chromatography electrospray multistage mass spectrometry. 28062629 7 7 theme mass 1499:1502 arg1 spectrometry 1504:1515 multistage mass spectrometry 1488:1515 multistage mass spectrometry 1488:1515 Differentially glycosylated variants were detected based on highly accurate mass determination and multistage mass spectrometry. 28062629 4 8 theme occurring 842:850 arg1 forms 852:856 the different naturally occurring forms 818:856 the different naturally occurring forms 818:856 There is a clear and urgent need to identify the glycosylation sites in the endogenously circulating peptides requested by the community to gain further insights into the different naturally occurring forms. 28062629 4 9 gly glycosylation 700:712 arg2 sites 714:718 the glycosylation sites 696:718 the glycosylation sites in the endogenously circulating peptides requested by the community to gain further insights into the different naturally occurring forms 696:856 There is a clear and urgent need to identify the glycosylation sites in the endogenously circulating peptides requested by the community to gain further insights into the different naturally occurring forms. 28062629 9 10 theme NT- 1845:1847 arg1 proBNP 1850:1855 human (NT-) proBNP 1838:1855 human (NT-) proBNP 1838:1855 CONCLUSIONS: Our results directly demonstrate for the first time a rather complex distribution of the endogenously circulating glycoforms by mass spectrometric analysis in HF patients, and show 9 glycosites in human (NT-) proBNP. 28062629 0 11 theme Severe 148:153 arg1 Failure 161:167 Severe Heart Failure 148:167 Severe Heart Failure 148:167 Unraveling the Molecular Complexity of O-Glycosylated Endogenous (N-Terminal) pro-B-Type Natriuretic Peptide Forms in Blood Plasma of Patients with Severe Heart Failure. 28062629 4 12 theme clear 662:666 arg1 need 679:682 a clear and urgent need 660:682 a clear and urgent need to identify the glycosylation sites in the endogenously circulating peptides requested by the community to gain further insights into the different naturally occurring forms 660:856 There is a clear and urgent need to identify the glycosylation sites in the endogenously circulating peptides requested by the community to gain further insights into the different naturally occurring forms. 28062629 5 13 theme glycosylation 872:884 arg1 proBNP 901:906 (NT-) proBNP 895:906 (NT-) proBNP (NT-proBNP and/or proBNP) 895:932 METHODS: The glycosylation sites of (NT-) proBNP (NT-proBNP and/or proBNP) were characterized in leftovers of heparinized plasma samples of severe HF patients (NT-proBNP: >10000 ng/L) by using tandem immunoaffinity purification, sequential exoglycosidase treatment for glycan trimming, β-elimination and Michael addition chemistry, as well as high-resolution nano-flow liquid chromatography electrospray multistage mass spectrometry. 28062629 5 13 theme glycosylation 872:884 arg1 sites 886:890 The glycosylation sites 868:890 The glycosylation sites of (NT-) proBNP (NT-proBNP and/or proBNP) 868:932 METHODS: The glycosylation sites of (NT-) proBNP (NT-proBNP and/or proBNP) were characterized in leftovers of heparinized plasma samples of severe HF patients (NT-proBNP: >10000 ng/L) by using tandem immunoaffinity purification, sequential exoglycosidase treatment for glycan trimming, β-elimination and Michael addition chemistry, as well as high-resolution nano-flow liquid chromatography electrospray multistage mass spectrometry. 28062629 9 14 theme circulating 1743:1753 arg1 glycoforms 1755:1764 the endogenously circulating glycoforms 1726:1764 the endogenously circulating glycoforms 1726:1764 CONCLUSIONS: Our results directly demonstrate for the first time a rather complex distribution of the endogenously circulating glycoforms by mass spectrometric analysis in HF patients, and show 9 glycosites in human (NT-) proBNP. 28062629 3 15 theme ProBNP 545:550 arg1 processing 552:561 ProBNP processing 545:561 ProBNP processing 545:561 ProBNP processing and immunoassay response are related to O-linked glycosylation of NT-proBNP and proBNP. 28062629 1 16 theme pro-B-type 204:213 arg1 biomarkers 324:333 biomarkers 324:333 biomarkers for diagnosis, prognosis, and disease monitoring of heart failure (HF) 324:404 BACKGROUND: Currently, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and its physiologically active counterpart, BNP, are most frequently used as biomarkers for diagnosis, prognosis, and disease monitoring of heart failure (HF). 28062629 1 16 theme pro-B-type 204:213 arg1 counterpart 278:288 its physiologically active counterpart 251:288 its physiologically active counterpart 251:288 BACKGROUND: Currently, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and its physiologically active counterpart, BNP, are most frequently used as biomarkers for diagnosis, prognosis, and disease monitoring of heart failure (HF). 28062629 1 16 theme pro-B-type 204:213 arg1 NT-proBNP 236:244 NT-proBNP 236:244 NT-proBNP 236:244 BACKGROUND: Currently, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and its physiologically active counterpart, BNP, are most frequently used as biomarkers for diagnosis, prognosis, and disease monitoring of heart failure (HF). 28062629 1 16 theme pro-B-type 204:213 arg1 peptide 227:233 N-terminal pro-B-type natriuretic peptide 193:233 N-terminal pro-B-type natriuretic peptide (NT-proBNP) 193:245 BACKGROUND: Currently, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and its physiologically active counterpart, BNP, are most frequently used as biomarkers for diagnosis, prognosis, and disease monitoring of heart failure (HF). 28062629 6 17 dep circulating 1348:1358 arg1 NT- 1361:1363 NT- 1361:1363 NT- 1361:1363 RESULTS: We describe 9 distinct glycosylation sites on circulating (NT-) proBNP in HF patients. 28062629 10 18 theme nonglycosylated 2015:2029 arg1 forms 2031:2035 mostly nonglycosylated forms 2008:2035 mostly nonglycosylated forms 2008:2035 This information may also have an impact on commercial immunoassays applying antibodies specific for the central region of (NT-) proBNP, which detect mostly nonglycosylated forms. 28062629 0 19 theme Patients 134:141 arg1 Plasma 124:129 Blood Plasma 118:129 Blood Plasma of Patients with Severe Heart Failure 118:167 Unraveling the Molecular Complexity of O-Glycosylated Endogenous (N-Terminal) pro-B-Type Natriuretic Peptide Forms in Blood Plasma of Patients with Severe Heart Failure. 28062629 1 20 theme heart 387:391 arg1 HF 402:403 HF 402:403 HF 402:403 BACKGROUND: Currently, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and its physiologically active counterpart, BNP, are most frequently used as biomarkers for diagnosis, prognosis, and disease monitoring of heart failure (HF). 28062629 1 20 theme heart 387:391 arg1 failure 393:399 heart failure 387:399 heart failure (HF) 387:404 BACKGROUND: Currently, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and its physiologically active counterpart, BNP, are most frequently used as biomarkers for diagnosis, prognosis, and disease monitoring of heart failure (HF). 28062629 9 21 theme spectrometric 1774:1786 arg1 analysis 1788:1795 mass spectrometric analysis 1769:1795 mass spectrometric analysis in HF patients 1769:1810 CONCLUSIONS: Our results directly demonstrate for the first time a rather complex distribution of the endogenously circulating glycoforms by mass spectrometric analysis in HF patients, and show 9 glycosites in human (NT-) proBNP. 28062629 6 22 theme glycosylation 1325:1337 arg1 sites 1339:1343 9 distinct glycosylation sites 1314:1343 9 distinct glycosylation sites on circulating (NT-) proBNP in HF patients 1314:1386 RESULTS: We describe 9 distinct glycosylation sites on circulating (NT-) proBNP in HF patients. 28062629 5 23 theme NT-proBNP 1019:1027 arg1 ng/L 1037:1040 NT-proBNP: >10000 ng/L 1019:1040 NT-proBNP: >10000 ng/L 1019:1040 METHODS: The glycosylation sites of (NT-) proBNP (NT-proBNP and/or proBNP) were characterized in leftovers of heparinized plasma samples of severe HF patients (NT-proBNP: >10000 ng/L) by using tandem immunoaffinity purification, sequential exoglycosidase treatment for glycan trimming, β-elimination and Michael addition chemistry, as well as high-resolution nano-flow liquid chromatography electrospray multistage mass spectrometry. 28062629 5 23 theme NT-proBNP 1019:1027 arg1 patients 1009:1016 severe HF patients 999:1016 severe HF patients (NT-proBNP: >10000 ng/L) 999:1041 METHODS: The glycosylation sites of (NT-) proBNP (NT-proBNP and/or proBNP) were characterized in leftovers of heparinized plasma samples of severe HF patients (NT-proBNP: >10000 ng/L) by using tandem immunoaffinity purification, sequential exoglycosidase treatment for glycan trimming, β-elimination and Michael addition chemistry, as well as high-resolution nano-flow liquid chromatography electrospray multistage mass spectrometry. 28062629 5 24 theme proBNP 901:906 arg1 proBNP 901:906 (NT-) proBNP 895:906 (NT-) proBNP (NT-proBNP and/or proBNP) 895:932 METHODS: The glycosylation sites of (NT-) proBNP (NT-proBNP and/or proBNP) were characterized in leftovers of heparinized plasma samples of severe HF patients (NT-proBNP: >10000 ng/L) by using tandem immunoaffinity purification, sequential exoglycosidase treatment for glycan trimming, β-elimination and Michael addition chemistry, as well as high-resolution nano-flow liquid chromatography electrospray multistage mass spectrometry. 28062629 5 24 theme proBNP 901:906 arg1 sites 886:890 The glycosylation sites 868:890 The glycosylation sites of (NT-) proBNP (NT-proBNP and/or proBNP) 868:932 METHODS: The glycosylation sites of (NT-) proBNP (NT-proBNP and/or proBNP) were characterized in leftovers of heparinized plasma samples of severe HF patients (NT-proBNP: >10000 ng/L) by using tandem immunoaffinity purification, sequential exoglycosidase treatment for glycan trimming, β-elimination and Michael addition chemistry, as well as high-resolution nano-flow liquid chromatography electrospray multistage mass spectrometry. 28062629 0 25 with Patients 134:141 arg1 Failure 161:167 Severe Heart Failure 148:167 Severe Heart Failure 148:167 Unraveling the Molecular Complexity of O-Glycosylated Endogenous (N-Terminal) pro-B-Type Natriuretic Peptide Forms in Blood Plasma of Patients with Severe Heart Failure. 28062629 9 26 gly glycosites 1824:1833 arg2 glycosites 1824:1833 9 glycosites 1822:1833 9 glycosites in human (NT-) proBNP 1822:1855 CONCLUSIONS: Our results directly demonstrate for the first time a rather complex distribution of the endogenously circulating glycoforms by mass spectrometric analysis in HF patients, and show 9 glycosites in human (NT-) proBNP. 28062629 4 27 theme urgent 672:677 arg1 need 679:682 a clear and urgent need 660:682 a clear and urgent need to identify the glycosylation sites in the endogenously circulating peptides requested by the community to gain further insights into the different naturally occurring forms 660:856 There is a clear and urgent need to identify the glycosylation sites in the endogenously circulating peptides requested by the community to gain further insights into the different naturally occurring forms. 28062629 0 28 theme N-Terminal 66:75 arg1 Peptide 101:107 O-Glycosylated Endogenous (N-Terminal) pro-B-Type Natriuretic Peptide 39:107 O-Glycosylated Endogenous (N-Terminal) pro-B-Type Natriuretic Peptide Forms 39:113 Unraveling the Molecular Complexity of O-Glycosylated Endogenous (N-Terminal) pro-B-Type Natriuretic Peptide Forms in Blood Plasma of Patients with Severe Heart Failure. 28062629 5 29 theme exoglycosidase 1099:1112 arg1 treatment 1114:1122 sequential exoglycosidase treatment 1088:1122 sequential exoglycosidase treatment for glycan trimming, β-elimination and Michael addition chemistry 1088:1188 METHODS: The glycosylation sites of (NT-) proBNP (NT-proBNP and/or proBNP) were characterized in leftovers of heparinized plasma samples of severe HF patients (NT-proBNP: >10000 ng/L) by using tandem immunoaffinity purification, sequential exoglycosidase treatment for glycan trimming, β-elimination and Michael addition chemistry, as well as high-resolution nano-flow liquid chromatography electrospray multistage mass spectrometry. 28062629 5 29 theme exoglycosidase 1099:1112 arg1 purification 1074:1085 tandem immunoaffinity purification 1052:1085 tandem immunoaffinity purification 1052:1085 METHODS: The glycosylation sites of (NT-) proBNP (NT-proBNP and/or proBNP) were characterized in leftovers of heparinized plasma samples of severe HF patients (NT-proBNP: >10000 ng/L) by using tandem immunoaffinity purification, sequential exoglycosidase treatment for glycan trimming, β-elimination and Michael addition chemistry, as well as high-resolution nano-flow liquid chromatography electrospray multistage mass spectrometry. 28062629 3 30 theme O-linked 603:610 arg1 glycosylation 612:624 O-linked glycosylation 603:624 O-linked glycosylation of NT-proBNP and proBNP 603:648 ProBNP processing and immunoassay response are related to O-linked glycosylation of NT-proBNP and proBNP. 28062629 9 31 from analysis 1788:1795 arg1 patients 1803:1810 HF patients 1800:1810 HF patients 1800:1810 CONCLUSIONS: Our results directly demonstrate for the first time a rather complex distribution of the endogenously circulating glycoforms by mass spectrometric analysis in HF patients, and show 9 glycosites in human (NT-) proBNP. 28062629 5 32 theme mass 1274:1277 arg1 spectrometry 1279:1290 high-resolution nano-flow liquid chromatography electrospray multistage mass spectrometry 1202:1290 high-resolution nano-flow liquid chromatography electrospray multistage mass spectrometry 1202:1290 METHODS: The glycosylation sites of (NT-) proBNP (NT-proBNP and/or proBNP) were characterized in leftovers of heparinized plasma samples of severe HF patients (NT-proBNP: >10000 ng/L) by using tandem immunoaffinity purification, sequential exoglycosidase treatment for glycan trimming, β-elimination and Michael addition chemistry, as well as high-resolution nano-flow liquid chromatography electrospray multistage mass spectrometry. 28062629 0 33 theme pro-B-Type 78:87 arg1 Peptide 101:107 O-Glycosylated Endogenous (N-Terminal) pro-B-Type Natriuretic Peptide 39:107 O-Glycosylated Endogenous (N-Terminal) pro-B-Type Natriuretic Peptide Forms 39:113 Unraveling the Molecular Complexity of O-Glycosylated Endogenous (N-Terminal) pro-B-Type Natriuretic Peptide Forms in Blood Plasma of Patients with Severe Heart Failure. 28062629 5 34 theme NT- 896:898 arg1 proBNP 901:906 (NT-) proBNP 895:906 (NT-) proBNP (NT-proBNP and/or proBNP) 895:932 METHODS: The glycosylation sites of (NT-) proBNP (NT-proBNP and/or proBNP) were characterized in leftovers of heparinized plasma samples of severe HF patients (NT-proBNP: >10000 ng/L) by using tandem immunoaffinity purification, sequential exoglycosidase treatment for glycan trimming, β-elimination and Michael addition chemistry, as well as high-resolution nano-flow liquid chromatography electrospray multistage mass spectrometry. 28062629 0 35 theme Peptide 101:107 arg1 Forms 109:113 O-Glycosylated Endogenous (N-Terminal) pro-B-Type Natriuretic Peptide Forms 39:113 O-Glycosylated Endogenous (N-Terminal) pro-B-Type Natriuretic Peptide Forms 39:113 Unraveling the Molecular Complexity of O-Glycosylated Endogenous (N-Terminal) pro-B-Type Natriuretic Peptide Forms in Blood Plasma of Patients with Severe Heart Failure. 28062629 5 36 theme immunoaffinity 1059:1072 arg1 treatment 1114:1122 sequential exoglycosidase treatment 1088:1122 sequential exoglycosidase treatment for glycan trimming, β-elimination and Michael addition chemistry 1088:1188 METHODS: The glycosylation sites of (NT-) proBNP (NT-proBNP and/or proBNP) were characterized in leftovers of heparinized plasma samples of severe HF patients (NT-proBNP: >10000 ng/L) by using tandem immunoaffinity purification, sequential exoglycosidase treatment for glycan trimming, β-elimination and Michael addition chemistry, as well as high-resolution nano-flow liquid chromatography electrospray multistage mass spectrometry. 28062629 5 36 theme immunoaffinity 1059:1072 arg1 purification 1074:1085 tandem immunoaffinity purification 1052:1085 tandem immunoaffinity purification 1052:1085 METHODS: The glycosylation sites of (NT-) proBNP (NT-proBNP and/or proBNP) were characterized in leftovers of heparinized plasma samples of severe HF patients (NT-proBNP: >10000 ng/L) by using tandem immunoaffinity purification, sequential exoglycosidase treatment for glycan trimming, β-elimination and Michael addition chemistry, as well as high-resolution nano-flow liquid chromatography electrospray multistage mass spectrometry. 28062629 8 37 gly nonglycosylated 1586:1600 arg1 form 1602:1605 a nonglycosylated form 1584:1605 a nonglycosylated form 1584:1605 Remarkably, for each of the identified proteolytic glycopeptides, a nonglycosylated form also was detectable. 28062629 8 37 gly nonglycosylated 1586:1600 arg1 detectable 1616:1625 detectable 1616:1625 detectable 1616:1625 Remarkably, for each of the identified proteolytic glycopeptides, a nonglycosylated form also was detectable. 28062629 8 38 theme identified 1546:1555 arg1 glycopeptides 1569:1581 the identified proteolytic glycopeptides 1542:1581 the identified proteolytic glycopeptides 1542:1581 Remarkably, for each of the identified proteolytic glycopeptides, a nonglycosylated form also was detectable. 28062629 2 39 theme BNP 432:434 arg1 immunoassays 436:447 Commercial NT-proBNP and BNP immunoassays 407:447 Commercial NT-proBNP and BNP immunoassays 407:447 Commercial NT-proBNP and BNP immunoassays cross-react to varying degrees with unprocessed proBNP, which is also found in the circulation. 28062629 5 40 theme Michael 1163:1169 arg1 addition 1171:1178 Michael addition 1163:1178 Michael addition 1163:1178 METHODS: The glycosylation sites of (NT-) proBNP (NT-proBNP and/or proBNP) were characterized in leftovers of heparinized plasma samples of severe HF patients (NT-proBNP: >10000 ng/L) by using tandem immunoaffinity purification, sequential exoglycosidase treatment for glycan trimming, β-elimination and Michael addition chemistry, as well as high-resolution nano-flow liquid chromatography electrospray multistage mass spectrometry. 28062629 2 41 theme NT-proBNP 418:426 arg1 immunoassays 436:447 Commercial NT-proBNP and BNP immunoassays 407:447 Commercial NT-proBNP and BNP immunoassays 407:447 Commercial NT-proBNP and BNP immunoassays cross-react to varying degrees with unprocessed proBNP, which is also found in the circulation. 28062629 4 42 theme circulating 740:750 arg1 peptides 752:759 the endogenously circulating peptides 723:759 the endogenously circulating peptides requested by the community to gain further insights into the different naturally occurring forms 723:856 There is a clear and urgent need to identify the glycosylation sites in the endogenously circulating peptides requested by the community to gain further insights into the different naturally occurring forms. 28062629 0 43 theme Molecular 15:23 arg1 Complexity 25:34 the Molecular Complexity 11:34 the Molecular Complexity of O-Glycosylated Endogenous (N-Terminal) pro-B-Type Natriuretic Peptide Forms in Blood Plasma of Patients with Severe Heart Failure 11:167 Unraveling the Molecular Complexity of O-Glycosylated Endogenous (N-Terminal) pro-B-Type Natriuretic Peptide Forms in Blood Plasma of Patients with Severe Heart Failure. 28062629 2 44 located found 519:523 arg1 circulation 532:542 the circulation 528:542 the circulation 528:542 Commercial NT-proBNP and BNP immunoassays cross-react to varying degrees with unprocessed proBNP, which is also found in the circulation. 28062629 2 44 located found 519:523 arg2 proBNP 497:502 unprocessed proBNP 485:502 unprocessed proBNP 485:502 Commercial NT-proBNP and BNP immunoassays cross-react to varying degrees with unprocessed proBNP, which is also found in the circulation. 28062629 2 45 theme varying 464:470 arg1 degrees 472:478 varying degrees 464:478 varying degrees 464:478 Commercial NT-proBNP and BNP immunoassays cross-react to varying degrees with unprocessed proBNP, which is also found in the circulation. 28062629 5 46 theme HF 1006:1007 arg1 ng/L 1037:1040 NT-proBNP: >10000 ng/L 1019:1040 NT-proBNP: >10000 ng/L 1019:1040 METHODS: The glycosylation sites of (NT-) proBNP (NT-proBNP and/or proBNP) were characterized in leftovers of heparinized plasma samples of severe HF patients (NT-proBNP: >10000 ng/L) by using tandem immunoaffinity purification, sequential exoglycosidase treatment for glycan trimming, β-elimination and Michael addition chemistry, as well as high-resolution nano-flow liquid chromatography electrospray multistage mass spectrometry. 28062629 5 46 theme HF 1006:1007 arg1 patients 1009:1016 severe HF patients 999:1016 severe HF patients (NT-proBNP: >10000 ng/L) 999:1041 METHODS: The glycosylation sites of (NT-) proBNP (NT-proBNP and/or proBNP) were characterized in leftovers of heparinized plasma samples of severe HF patients (NT-proBNP: >10000 ng/L) by using tandem immunoaffinity purification, sequential exoglycosidase treatment for glycan trimming, β-elimination and Michael addition chemistry, as well as high-resolution nano-flow liquid chromatography electrospray multistage mass spectrometry. 28062629 4 47 theme different 822:830 arg1 forms 852:856 the different naturally occurring forms 818:856 the different naturally occurring forms 818:856 There is a clear and urgent need to identify the glycosylation sites in the endogenously circulating peptides requested by the community to gain further insights into the different naturally occurring forms. 28062629 0 48 theme Endogenous 54:63 arg1 Peptide 101:107 O-Glycosylated Endogenous (N-Terminal) pro-B-Type Natriuretic Peptide 39:107 O-Glycosylated Endogenous (N-Terminal) pro-B-Type Natriuretic Peptide Forms 39:113 Unraveling the Molecular Complexity of O-Glycosylated Endogenous (N-Terminal) pro-B-Type Natriuretic Peptide Forms in Blood Plasma of Patients with Severe Heart Failure. 28062629 6 49 from sites 1339:1343 arg1 proBNP 1366:1371 circulating (NT-) proBNP 1348:1371 circulating (NT-) proBNP in HF patients 1348:1386 RESULTS: We describe 9 distinct glycosylation sites on circulating (NT-) proBNP in HF patients. 28062629 5 50 theme nano-flow 1218:1226 arg1 spectrometry 1279:1290 high-resolution nano-flow liquid chromatography electrospray multistage mass spectrometry 1202:1290 high-resolution nano-flow liquid chromatography electrospray multistage mass spectrometry 1202:1290 METHODS: The glycosylation sites of (NT-) proBNP (NT-proBNP and/or proBNP) were characterized in leftovers of heparinized plasma samples of severe HF patients (NT-proBNP: >10000 ng/L) by using tandem immunoaffinity purification, sequential exoglycosidase treatment for glycan trimming, β-elimination and Michael addition chemistry, as well as high-resolution nano-flow liquid chromatography electrospray multistage mass spectrometry. 28062629 5 51 theme plasma 981:986 arg1 samples 988:994 heparinized plasma samples 969:994 heparinized plasma samples of severe HF patients (NT-proBNP: >10000 ng/L) 969:1041 METHODS: The glycosylation sites of (NT-) proBNP (NT-proBNP and/or proBNP) were characterized in leftovers of heparinized plasma samples of severe HF patients (NT-proBNP: >10000 ng/L) by using tandem immunoaffinity purification, sequential exoglycosidase treatment for glycan trimming, β-elimination and Michael addition chemistry, as well as high-resolution nano-flow liquid chromatography electrospray multistage mass spectrometry. 28062629 4 52 theme further 796:802 arg1 insights 804:811 further insights 796:811 further insights into the different naturally occurring forms 796:856 There is a clear and urgent need to identify the glycosylation sites in the endogenously circulating peptides requested by the community to gain further insights into the different naturally occurring forms. 28062629 5 53 theme chromatography 1235:1248 arg1 spectrometry 1279:1290 high-resolution nano-flow liquid chromatography electrospray multistage mass spectrometry 1202:1290 high-resolution nano-flow liquid chromatography electrospray multistage mass spectrometry 1202:1290 METHODS: The glycosylation sites of (NT-) proBNP (NT-proBNP and/or proBNP) were characterized in leftovers of heparinized plasma samples of severe HF patients (NT-proBNP: >10000 ng/L) by using tandem immunoaffinity purification, sequential exoglycosidase treatment for glycan trimming, β-elimination and Michael addition chemistry, as well as high-resolution nano-flow liquid chromatography electrospray multistage mass spectrometry. 28062629 9 54 theme first 1682:1686 arg1 time 1688:1691 the first time 1678:1691 the first time 1678:1691 CONCLUSIONS: Our results directly demonstrate for the first time a rather complex distribution of the endogenously circulating glycoforms by mass spectrometric analysis in HF patients, and show 9 glycosites in human (NT-) proBNP. 28062629 1 55 theme active 271:276 arg1 biomarkers 324:333 biomarkers 324:333 biomarkers for diagnosis, prognosis, and disease monitoring of heart failure (HF) 324:404 BACKGROUND: Currently, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and its physiologically active counterpart, BNP, are most frequently used as biomarkers for diagnosis, prognosis, and disease monitoring of heart failure (HF). 28062629 1 55 theme active 271:276 arg1 peptide 227:233 N-terminal pro-B-type natriuretic peptide 193:233 N-terminal pro-B-type natriuretic peptide (NT-proBNP) 193:245 BACKGROUND: Currently, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and its physiologically active counterpart, BNP, are most frequently used as biomarkers for diagnosis, prognosis, and disease monitoring of heart failure (HF). 28062629 1 55 theme active 271:276 arg1 BNP 291:293 BNP 291:293 BNP 291:293 BACKGROUND: Currently, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and its physiologically active counterpart, BNP, are most frequently used as biomarkers for diagnosis, prognosis, and disease monitoring of heart failure (HF). 28062629 1 55 theme active 271:276 arg1 counterpart 278:288 its physiologically active counterpart 251:288 its physiologically active counterpart 251:288 BACKGROUND: Currently, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and its physiologically active counterpart, BNP, are most frequently used as biomarkers for diagnosis, prognosis, and disease monitoring of heart failure (HF). 28062629 7 56 theme multistage 1488:1497 arg1 spectrometry 1504:1515 multistage mass spectrometry 1488:1515 multistage mass spectrometry 1488:1515 Differentially glycosylated variants were detected based on highly accurate mass determination and multistage mass spectrometry. 28062629 9 57 theme complex 1702:1708 arg1 distribution 1710:1721 a rather complex distribution 1693:1721 a rather complex distribution of the endogenously circulating glycoforms 1693:1764 CONCLUSIONS: Our results directly demonstrate for the first time a rather complex distribution of the endogenously circulating glycoforms by mass spectrometric analysis in HF patients, and show 9 glycosites in human (NT-) proBNP. 28062629 7 58 theme mass 1465:1468 arg1 determination 1470:1482 highly accurate mass determination 1449:1482 highly accurate mass determination 1449:1482 Differentially glycosylated variants were detected based on highly accurate mass determination and multistage mass spectrometry. 28062629 6 59 gly glycosylation 1325:1337 arg2 9 1314:1314 9 1314:1314 9 1314:1314 RESULTS: We describe 9 distinct glycosylation sites on circulating (NT-) proBNP in HF patients. 28062629 6 59 gly glycosylation 1325:1337 arg2 sites 1339:1343 9 distinct glycosylation sites 1314:1343 9 distinct glycosylation sites on circulating (NT-) proBNP in HF patients 1314:1386 RESULTS: We describe 9 distinct glycosylation sites on circulating (NT-) proBNP in HF patients. 28062629 3 60 gly glycosylation 612:624 arg1 proBNP 643:648 proBNP 643:648 proBNP 643:648 ProBNP processing and immunoassay response are related to O-linked glycosylation of NT-proBNP and proBNP. 28062629 3 60 gly glycosylation 612:624 arg1 NT-proBNP 629:637 NT-proBNP 629:637 NT-proBNP 629:637 ProBNP processing and immunoassay response are related to O-linked glycosylation of NT-proBNP and proBNP. 28062629 10 61 theme central 1963:1969 arg1 region 1971:1976 the central region 1959:1976 the central region of (NT-) proBNP, which detect mostly nonglycosylated forms 1959:2035 This information may also have an impact on commercial immunoassays applying antibodies specific for the central region of (NT-) proBNP, which detect mostly nonglycosylated forms. 28062629 10 62 theme proBNP 1987:1992 arg1 region 1971:1976 the central region 1959:1976 the central region of (NT-) proBNP, which detect mostly nonglycosylated forms 1959:2035 This information may also have an impact on commercial immunoassays applying antibodies specific for the central region of (NT-) proBNP, which detect mostly nonglycosylated forms. 28062629 1 63 theme N-terminal 193:202 arg1 biomarkers 324:333 biomarkers 324:333 biomarkers for diagnosis, prognosis, and disease monitoring of heart failure (HF) 324:404 BACKGROUND: Currently, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and its physiologically active counterpart, BNP, are most frequently used as biomarkers for diagnosis, prognosis, and disease monitoring of heart failure (HF). 28062629 1 63 theme N-terminal 193:202 arg1 counterpart 278:288 its physiologically active counterpart 251:288 its physiologically active counterpart 251:288 BACKGROUND: Currently, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and its physiologically active counterpart, BNP, are most frequently used as biomarkers for diagnosis, prognosis, and disease monitoring of heart failure (HF). 28062629 1 63 theme N-terminal 193:202 arg1 NT-proBNP 236:244 NT-proBNP 236:244 NT-proBNP 236:244 BACKGROUND: Currently, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and its physiologically active counterpart, BNP, are most frequently used as biomarkers for diagnosis, prognosis, and disease monitoring of heart failure (HF). 28062629 1 63 theme N-terminal 193:202 arg1 peptide 227:233 N-terminal pro-B-type natriuretic peptide 193:233 N-terminal pro-B-type natriuretic peptide (NT-proBNP) 193:245 BACKGROUND: Currently, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and its physiologically active counterpart, BNP, are most frequently used as biomarkers for diagnosis, prognosis, and disease monitoring of heart failure (HF). 28062629 9 64 theme glycoforms 1755:1764 arg1 distribution 1710:1721 a rather complex distribution 1693:1721 a rather complex distribution of the endogenously circulating glycoforms 1693:1764 CONCLUSIONS: Our results directly demonstrate for the first time a rather complex distribution of the endogenously circulating glycoforms by mass spectrometric analysis in HF patients, and show 9 glycosites in human (NT-) proBNP. 28062629 10 65 theme NT- 1982:1984 arg1 proBNP 1987:1992 (NT-) proBNP 1981:1992 (NT-) proBNP 1981:1992 This information may also have an impact on commercial immunoassays applying antibodies specific for the central region of (NT-) proBNP, which detect mostly nonglycosylated forms. 28062629 6 66 theme circulating 1348:1358 arg1 proBNP 1366:1371 circulating (NT-) proBNP 1348:1371 circulating (NT-) proBNP in HF patients 1348:1386 RESULTS: We describe 9 distinct glycosylation sites on circulating (NT-) proBNP in HF patients. 28062629 1 67 theme natriuretic 215:225 arg1 biomarkers 324:333 biomarkers 324:333 biomarkers for diagnosis, prognosis, and disease monitoring of heart failure (HF) 324:404 BACKGROUND: Currently, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and its physiologically active counterpart, BNP, are most frequently used as biomarkers for diagnosis, prognosis, and disease monitoring of heart failure (HF). 28062629 1 67 theme natriuretic 215:225 arg1 counterpart 278:288 its physiologically active counterpart 251:288 its physiologically active counterpart 251:288 BACKGROUND: Currently, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and its physiologically active counterpart, BNP, are most frequently used as biomarkers for diagnosis, prognosis, and disease monitoring of heart failure (HF). 28062629 1 67 theme natriuretic 215:225 arg1 NT-proBNP 236:244 NT-proBNP 236:244 NT-proBNP 236:244 BACKGROUND: Currently, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and its physiologically active counterpart, BNP, are most frequently used as biomarkers for diagnosis, prognosis, and disease monitoring of heart failure (HF). 28062629 1 67 theme natriuretic 215:225 arg1 peptide 227:233 N-terminal pro-B-type natriuretic peptide 193:233 N-terminal pro-B-type natriuretic peptide (NT-proBNP) 193:245 BACKGROUND: Currently, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and its physiologically active counterpart, BNP, are most frequently used as biomarkers for diagnosis, prognosis, and disease monitoring of heart failure (HF). 28062629 9 68 theme mass 1769:1772 arg1 analysis 1788:1795 mass spectrometric analysis 1769:1795 mass spectrometric analysis in HF patients 1769:1810 CONCLUSIONS: Our results directly demonstrate for the first time a rather complex distribution of the endogenously circulating glycoforms by mass spectrometric analysis in HF patients, and show 9 glycosites in human (NT-) proBNP. 28062629 7 69 theme glycosylated 1404:1415 arg1 variants 1417:1424 Differentially glycosylated variants 1389:1424 Differentially glycosylated variants 1389:1424 Differentially glycosylated variants were detected based on highly accurate mass determination and multistage mass spectrometry. 28062629 6 70 theme HF 1376:1377 arg1 patients 1379:1386 HF patients 1376:1386 HF patients 1376:1386 RESULTS: We describe 9 distinct glycosylation sites on circulating (NT-) proBNP in HF patients. 28062629 0 71 theme Heart 155:159 arg1 Failure 161:167 Severe Heart Failure 148:167 Severe Heart Failure 148:167 Unraveling the Molecular Complexity of O-Glycosylated Endogenous (N-Terminal) pro-B-Type Natriuretic Peptide Forms in Blood Plasma of Patients with Severe Heart Failure. 28062629 5 72 theme tandem 1052:1057 arg1 treatment 1114:1122 sequential exoglycosidase treatment 1088:1122 sequential exoglycosidase treatment for glycan trimming, β-elimination and Michael addition chemistry 1088:1188 METHODS: The glycosylation sites of (NT-) proBNP (NT-proBNP and/or proBNP) were characterized in leftovers of heparinized plasma samples of severe HF patients (NT-proBNP: >10000 ng/L) by using tandem immunoaffinity purification, sequential exoglycosidase treatment for glycan trimming, β-elimination and Michael addition chemistry, as well as high-resolution nano-flow liquid chromatography electrospray multistage mass spectrometry. 28062629 5 72 theme tandem 1052:1057 arg1 purification 1074:1085 tandem immunoaffinity purification 1052:1085 tandem immunoaffinity purification 1052:1085 METHODS: The glycosylation sites of (NT-) proBNP (NT-proBNP and/or proBNP) were characterized in leftovers of heparinized plasma samples of severe HF patients (NT-proBNP: >10000 ng/L) by using tandem immunoaffinity purification, sequential exoglycosidase treatment for glycan trimming, β-elimination and Michael addition chemistry, as well as high-resolution nano-flow liquid chromatography electrospray multistage mass spectrometry. 28062629 3 73 theme immunoassay 567:577 arg1 response 579:586 immunoassay response 567:586 immunoassay response 567:586 ProBNP processing and immunoassay response are related to O-linked glycosylation of NT-proBNP and proBNP. 28062629 6 74 theme distinct 1316:1323 arg1 sites 1339:1343 9 distinct glycosylation sites 1314:1343 9 distinct glycosylation sites on circulating (NT-) proBNP in HF patients 1314:1386 RESULTS: We describe 9 distinct glycosylation sites on circulating (NT-) proBNP in HF patients. 28062629 9 75 theme HF 1800:1801 arg1 patients 1803:1810 HF patients 1800:1810 HF patients 1800:1810 CONCLUSIONS: Our results directly demonstrate for the first time a rather complex distribution of the endogenously circulating glycoforms by mass spectrometric analysis in HF patients, and show 9 glycosites in human (NT-) proBNP. 28062629 4 76 theme glycosylation 700:712 arg1 sites 714:718 the glycosylation sites 696:718 the glycosylation sites in the endogenously circulating peptides requested by the community to gain further insights into the different naturally occurring forms 696:856 There is a clear and urgent need to identify the glycosylation sites in the endogenously circulating peptides requested by the community to gain further insights into the different naturally occurring forms. 28062629 2 77 theme unprocessed 485:495 arg1 proBNP 497:502 unprocessed proBNP 485:502 unprocessed proBNP 485:502 Commercial NT-proBNP and BNP immunoassays cross-react to varying degrees with unprocessed proBNP, which is also found in the circulation. 28062629 0 78 from Complexity 25:34 arg1 Plasma 124:129 Blood Plasma 118:129 Blood Plasma of Patients with Severe Heart Failure 118:167 Unraveling the Molecular Complexity of O-Glycosylated Endogenous (N-Terminal) pro-B-Type Natriuretic Peptide Forms in Blood Plasma of Patients with Severe Heart Failure. 28062629 5 79 theme multistage 1263:1272 arg1 spectrometry 1279:1290 high-resolution nano-flow liquid chromatography electrospray multistage mass spectrometry 1202:1290 high-resolution nano-flow liquid chromatography electrospray multistage mass spectrometry 1202:1290 METHODS: The glycosylation sites of (NT-) proBNP (NT-proBNP and/or proBNP) were characterized in leftovers of heparinized plasma samples of severe HF patients (NT-proBNP: >10000 ng/L) by using tandem immunoaffinity purification, sequential exoglycosidase treatment for glycan trimming, β-elimination and Michael addition chemistry, as well as high-resolution nano-flow liquid chromatography electrospray multistage mass spectrometry. 28062629 0 80 theme Natriuretic 89:99 arg1 Peptide 101:107 O-Glycosylated Endogenous (N-Terminal) pro-B-Type Natriuretic Peptide 39:107 O-Glycosylated Endogenous (N-Terminal) pro-B-Type Natriuretic Peptide Forms 39:113 Unraveling the Molecular Complexity of O-Glycosylated Endogenous (N-Terminal) pro-B-Type Natriuretic Peptide Forms in Blood Plasma of Patients with Severe Heart Failure. 28062629 8 81 gly glycopeptides 1569:1581 arg2 glycopeptides 1569:1581 the identified proteolytic glycopeptides 1542:1581 the identified proteolytic glycopeptides 1542:1581 Remarkably, for each of the identified proteolytic glycopeptides, a nonglycosylated form also was detectable. 28062629 6 82 from proBNP 1366:1371 arg1 patients 1379:1386 HF patients 1376:1386 HF patients 1376:1386 RESULTS: We describe 9 distinct glycosylation sites on circulating (NT-) proBNP in HF patients. 28062629 0 83 theme Forms 109:113 arg1 Complexity 25:34 the Molecular Complexity 11:34 the Molecular Complexity of O-Glycosylated Endogenous (N-Terminal) pro-B-Type Natriuretic Peptide Forms in Blood Plasma of Patients with Severe Heart Failure 11:167 Unraveling the Molecular Complexity of O-Glycosylated Endogenous (N-Terminal) pro-B-Type Natriuretic Peptide Forms in Blood Plasma of Patients with Severe Heart Failure. 28062629 5 84 theme glycan 1128:1133 arg1 trimming 1135:1142 glycan trimming 1128:1142 glycan trimming 1128:1142 METHODS: The glycosylation sites of (NT-) proBNP (NT-proBNP and/or proBNP) were characterized in leftovers of heparinized plasma samples of severe HF patients (NT-proBNP: >10000 ng/L) by using tandem immunoaffinity purification, sequential exoglycosidase treatment for glycan trimming, β-elimination and Michael addition chemistry, as well as high-resolution nano-flow liquid chromatography electrospray multistage mass spectrometry. 28062629 8 85 theme proteolytic 1557:1567 arg1 glycopeptides 1569:1581 the identified proteolytic glycopeptides 1542:1581 the identified proteolytic glycopeptides 1542:1581 Remarkably, for each of the identified proteolytic glycopeptides, a nonglycosylated form also was detectable. 28062629 10 86 gly nonglycosylated 2015:2029 arg1 forms 2031:2035 mostly nonglycosylated forms 2008:2035 mostly nonglycosylated forms 2008:2035 This information may also have an impact on commercial immunoassays applying antibodies specific for the central region of (NT-) proBNP, which detect mostly nonglycosylated forms. 28062629 0 87 theme Blood 118:122 arg1 Plasma 124:129 Blood Plasma 118:129 Blood Plasma of Patients with Severe Heart Failure 118:167 Unraveling the Molecular Complexity of O-Glycosylated Endogenous (N-Terminal) pro-B-Type Natriuretic Peptide Forms in Blood Plasma of Patients with Severe Heart Failure. 28062629 9 88 theme human 1838:1842 arg1 proBNP 1850:1855 human (NT-) proBNP 1838:1855 human (NT-) proBNP 1838:1855 CONCLUSIONS: Our results directly demonstrate for the first time a rather complex distribution of the endogenously circulating glycoforms by mass spectrometric analysis in HF patients, and show 9 glycosites in human (NT-) proBNP. 28062629 5 89 dep trimming 1135:1142 arg1 chemistry 1180:1188 chemistry 1180:1188 chemistry 1180:1188 METHODS: The glycosylation sites of (NT-) proBNP (NT-proBNP and/or proBNP) were characterized in leftovers of heparinized plasma samples of severe HF patients (NT-proBNP: >10000 ng/L) by using tandem immunoaffinity purification, sequential exoglycosidase treatment for glycan trimming, β-elimination and Michael addition chemistry, as well as high-resolution nano-flow liquid chromatography electrospray multistage mass spectrometry. 28062629 7 90 gly glycosylated 1404:1415 arg1 variants 1417:1424 Differentially glycosylated variants 1389:1424 Differentially glycosylated variants 1389:1424 Differentially glycosylated variants were detected based on highly accurate mass determination and multistage mass spectrometry. 28062629 5 91 dep proBNP 901:906 arg1 proBNP 926:931 proBNP 926:931 proBNP 926:931 METHODS: The glycosylation sites of (NT-) proBNP (NT-proBNP and/or proBNP) were characterized in leftovers of heparinized plasma samples of severe HF patients (NT-proBNP: >10000 ng/L) by using tandem immunoaffinity purification, sequential exoglycosidase treatment for glycan trimming, β-elimination and Michael addition chemistry, as well as high-resolution nano-flow liquid chromatography electrospray multistage mass spectrometry. 28062629 5 91 dep proBNP 901:906 arg1 NT-proBNP 909:917 NT-proBNP 909:917 NT-proBNP 909:917 METHODS: The glycosylation sites of (NT-) proBNP (NT-proBNP and/or proBNP) were characterized in leftovers of heparinized plasma samples of severe HF patients (NT-proBNP: >10000 ng/L) by using tandem immunoaffinity purification, sequential exoglycosidase treatment for glycan trimming, β-elimination and Michael addition chemistry, as well as high-resolution nano-flow liquid chromatography electrospray multistage mass spectrometry. 28062629 5 92 theme sequential 1088:1097 arg1 treatment 1114:1122 sequential exoglycosidase treatment 1088:1122 sequential exoglycosidase treatment for glycan trimming, β-elimination and Michael addition chemistry 1088:1188 METHODS: The glycosylation sites of (NT-) proBNP (NT-proBNP and/or proBNP) were characterized in leftovers of heparinized plasma samples of severe HF patients (NT-proBNP: >10000 ng/L) by using tandem immunoaffinity purification, sequential exoglycosidase treatment for glycan trimming, β-elimination and Michael addition chemistry, as well as high-resolution nano-flow liquid chromatography electrospray multistage mass spectrometry. 28062629 5 92 theme sequential 1088:1097 arg1 purification 1074:1085 tandem immunoaffinity purification 1052:1085 tandem immunoaffinity purification 1052:1085 METHODS: The glycosylation sites of (NT-) proBNP (NT-proBNP and/or proBNP) were characterized in leftovers of heparinized plasma samples of severe HF patients (NT-proBNP: >10000 ng/L) by using tandem immunoaffinity purification, sequential exoglycosidase treatment for glycan trimming, β-elimination and Michael addition chemistry, as well as high-resolution nano-flow liquid chromatography electrospray multistage mass spectrometry. 28062629 3 93 link O-linked 603:610 arg1 glycosylation 612:624 O-linked glycosylation 603:624 O-linked glycosylation of NT-proBNP and proBNP 603:648 ProBNP processing and immunoassay response are related to O-linked glycosylation of NT-proBNP and proBNP. 28062629 8 94 theme nonglycosylated 1586:1600 arg1 form 1602:1605 a nonglycosylated form 1584:1605 a nonglycosylated form 1584:1605 Remarkably, for each of the identified proteolytic glycopeptides, a nonglycosylated form also was detectable. 28062629 8 94 theme nonglycosylated 1586:1600 arg1 detectable 1616:1625 detectable 1616:1625 detectable 1616:1625 Remarkably, for each of the identified proteolytic glycopeptides, a nonglycosylated form also was detectable. 28062629 2 95 theme Commercial 407:416 arg1 immunoassays 436:447 Commercial NT-proBNP and BNP immunoassays 407:447 Commercial NT-proBNP and BNP immunoassays 407:447 Commercial NT-proBNP and BNP immunoassays cross-react to varying degrees with unprocessed proBNP, which is also found in the circulation. 28062629 3 96 theme proBNP 643:648 arg1 glycosylation 612:624 O-linked glycosylation 603:624 O-linked glycosylation of NT-proBNP and proBNP 603:648 ProBNP processing and immunoassay response are related to O-linked glycosylation of NT-proBNP and proBNP. 28062629 0 97 theme O-Glycosylated 39:52 arg1 Peptide 101:107 O-Glycosylated Endogenous (N-Terminal) pro-B-Type Natriuretic Peptide 39:107 O-Glycosylated Endogenous (N-Terminal) pro-B-Type Natriuretic Peptide Forms 39:113 Unraveling the Molecular Complexity of O-Glycosylated Endogenous (N-Terminal) pro-B-Type Natriuretic Peptide Forms in Blood Plasma of Patients with Severe Heart Failure. 28062629 5 98 theme severe 999:1004 arg1 ng/L 1037:1040 NT-proBNP: >10000 ng/L 1019:1040 NT-proBNP: >10000 ng/L 1019:1040 METHODS: The glycosylation sites of (NT-) proBNP (NT-proBNP and/or proBNP) were characterized in leftovers of heparinized plasma samples of severe HF patients (NT-proBNP: >10000 ng/L) by using tandem immunoaffinity purification, sequential exoglycosidase treatment for glycan trimming, β-elimination and Michael addition chemistry, as well as high-resolution nano-flow liquid chromatography electrospray multistage mass spectrometry. 28062629 5 98 theme severe 999:1004 arg1 patients 1009:1016 severe HF patients 999:1016 severe HF patients (NT-proBNP: >10000 ng/L) 999:1041 METHODS: The glycosylation sites of (NT-) proBNP (NT-proBNP and/or proBNP) were characterized in leftovers of heparinized plasma samples of severe HF patients (NT-proBNP: >10000 ng/L) by using tandem immunoaffinity purification, sequential exoglycosidase treatment for glycan trimming, β-elimination and Michael addition chemistry, as well as high-resolution nano-flow liquid chromatography electrospray multistage mass spectrometry. 28062629 3 99 theme NT-proBNP 629:637 arg1 glycosylation 612:624 O-linked glycosylation 603:624 O-linked glycosylation of NT-proBNP and proBNP 603:648 ProBNP processing and immunoassay response are related to O-linked glycosylation of NT-proBNP and proBNP. 28062629 9 100 from glycosites 1824:1833 arg1 proBNP 1850:1855 human (NT-) proBNP 1838:1855 human (NT-) proBNP 1838:1855 CONCLUSIONS: Our results directly demonstrate for the first time a rather complex distribution of the endogenously circulating glycoforms by mass spectrometric analysis in HF patients, and show 9 glycosites in human (NT-) proBNP. 28062629 5 101 theme patients 1009:1016 arg1 samples 988:994 heparinized plasma samples 969:994 heparinized plasma samples of severe HF patients (NT-proBNP: >10000 ng/L) 969:1041 METHODS: The glycosylation sites of (NT-) proBNP (NT-proBNP and/or proBNP) were characterized in leftovers of heparinized plasma samples of severe HF patients (NT-proBNP: >10000 ng/L) by using tandem immunoaffinity purification, sequential exoglycosidase treatment for glycan trimming, β-elimination and Michael addition chemistry, as well as high-resolution nano-flow liquid chromatography electrospray multistage mass spectrometry. 28062629 4 102 from sites 714:718 arg1 peptides 752:759 the endogenously circulating peptides 723:759 the endogenously circulating peptides requested by the community to gain further insights into the different naturally occurring forms 723:856 There is a clear and urgent need to identify the glycosylation sites in the endogenously circulating peptides requested by the community to gain further insights into the different naturally occurring forms. 28062629 5 103 theme heparinized 969:979 arg1 samples 988:994 heparinized plasma samples 969:994 heparinized plasma samples of severe HF patients (NT-proBNP: >10000 ng/L) 969:1041 METHODS: The glycosylation sites of (NT-) proBNP (NT-proBNP and/or proBNP) were characterized in leftovers of heparinized plasma samples of severe HF patients (NT-proBNP: >10000 ng/L) by using tandem immunoaffinity purification, sequential exoglycosidase treatment for glycan trimming, β-elimination and Michael addition chemistry, as well as high-resolution nano-flow liquid chromatography electrospray multistage mass spectrometry. 28062629 10 104 contain have 1884:1887 arg2 impact 1892:1897 an impact 1889:1897 an impact 1889:1897 This information may also have an impact on commercial immunoassays applying antibodies specific for the central region of (NT-) proBNP, which detect mostly nonglycosylated forms. 28062629 10 104 contain have 1884:1887 arg1 information 1863:1873 This information 1858:1873 This information 1858:1873 This information may also have an impact on commercial immunoassays applying antibodies specific for the central region of (NT-) proBNP, which detect mostly nonglycosylated forms. 28062629 10 105 theme commercial 1902:1911 arg1 immunoassays 1913:1924 commercial immunoassays 1902:1924 commercial immunoassays applying antibodies specific for the central region of (NT-) proBNP, which detect mostly nonglycosylated forms 1902:2035 This information may also have an impact on commercial immunoassays applying antibodies specific for the central region of (NT-) proBNP, which detect mostly nonglycosylated forms. 28062629 5 106 theme liquid 1228:1233 arg1 spectrometry 1279:1290 high-resolution nano-flow liquid chromatography electrospray multistage mass spectrometry 1202:1290 high-resolution nano-flow liquid chromatography electrospray multistage mass spectrometry 1202:1290 METHODS: The glycosylation sites of (NT-) proBNP (NT-proBNP and/or proBNP) were characterized in leftovers of heparinized plasma samples of severe HF patients (NT-proBNP: >10000 ng/L) by using tandem immunoaffinity purification, sequential exoglycosidase treatment for glycan trimming, β-elimination and Michael addition chemistry, as well as high-resolution nano-flow liquid chromatography electrospray multistage mass spectrometry. 28062629 5 107 theme samples 988:994 arg1 leftovers 956:964 leftovers 956:964 leftovers of heparinized plasma samples of severe HF patients (NT-proBNP: >10000 ng/L) 956:1041 METHODS: The glycosylation sites of (NT-) proBNP (NT-proBNP and/or proBNP) were characterized in leftovers of heparinized plasma samples of severe HF patients (NT-proBNP: >10000 ng/L) by using tandem immunoaffinity purification, sequential exoglycosidase treatment for glycan trimming, β-elimination and Michael addition chemistry, as well as high-resolution nano-flow liquid chromatography electrospray multistage mass spectrometry. 28062629 5 108 theme electrospray 1250:1261 arg1 spectrometry 1279:1290 high-resolution nano-flow liquid chromatography electrospray multistage mass spectrometry 1202:1290 high-resolution nano-flow liquid chromatography electrospray multistage mass spectrometry 1202:1290 METHODS: The glycosylation sites of (NT-) proBNP (NT-proBNP and/or proBNP) were characterized in leftovers of heparinized plasma samples of severe HF patients (NT-proBNP: >10000 ng/L) by using tandem immunoaffinity purification, sequential exoglycosidase treatment for glycan trimming, β-elimination and Michael addition chemistry, as well as high-resolution nano-flow liquid chromatography electrospray multistage mass spectrometry. 25392222 1 0 theme NS1 267:269 arg1 protein 271:277 the West Nile virus NS1 protein 247:277 the West Nile virus NS1 protein 247:277 We have previously shown that ablation of the three N-linked glycosylation sites in the West Nile virus NS1 protein completely attenuates mouse neuroinvasiveness (≥1,000,000 PFU). 25392222 3 1 theme attenuation 522:532 arg1 lack 539:542 a lack 537:542 a lack 537:542 The results suggest that the mechanism of attenuation is a lack of NS1 glycosylation, which blocks efficient replication, maturation, and NS1 secretion from the endoplasmic reticulum and results in changes to the virus-induced ultrastructure. 25392222 3 1 theme attenuation 522:532 arg1 mechanism 509:517 the mechanism 505:517 the mechanism of attenuation 505:532 The results suggest that the mechanism of attenuation is a lack of NS1 glycosylation, which blocks efficient replication, maturation, and NS1 secretion from the endoplasmic reticulum and results in changes to the virus-induced ultrastructure. 25392222 0 2 theme protein 125:131 arg1 accumulation 109:120 accumulation 109:120 accumulation of protein in the endoplasmic reticulum 109:160 Attenuated West Nile virus mutant NS1130-132QQA/175A/207A exhibits virus-induced ultrastructural changes and accumulation of protein in the endoplasmic reticulum. 25392222 0 2 theme protein 125:131 arg1 changes 97:103 virus-induced ultrastructural changes 67:103 virus-induced ultrastructural changes 67:103 Attenuated West Nile virus mutant NS1130-132QQA/175A/207A exhibits virus-induced ultrastructural changes and accumulation of protein in the endoplasmic reticulum. 25392222 3 3 theme virus-induced 693:705 arg1 ultrastructure 707:720 the virus-induced ultrastructure 689:720 the virus-induced ultrastructure 689:720 The results suggest that the mechanism of attenuation is a lack of NS1 glycosylation, which blocks efficient replication, maturation, and NS1 secretion from the endoplasmic reticulum and results in changes to the virus-induced ultrastructure. 25392222 1 4 link N-linked 215:222 arg1 sites 238:242 the three N-linked glycosylation sites 205:242 the three N-linked glycosylation sites 205:242 We have previously shown that ablation of the three N-linked glycosylation sites in the West Nile virus NS1 protein completely attenuates mouse neuroinvasiveness (≥1,000,000 PFU). 25392222 3 5 theme NS1 547:549 arg1 glycosylation 551:563 NS1 glycosylation 547:563 NS1 glycosylation 547:563 The results suggest that the mechanism of attenuation is a lack of NS1 glycosylation, which blocks efficient replication, maturation, and NS1 secretion from the endoplasmic reticulum and results in changes to the virus-induced ultrastructure. 25392222 3 6 theme glycosylation 551:563 arg1 lack 539:542 a lack 537:542 a lack 537:542 The results suggest that the mechanism of attenuation is a lack of NS1 glycosylation, which blocks efficient replication, maturation, and NS1 secretion from the endoplasmic reticulum and results in changes to the virus-induced ultrastructure. 25392222 3 6 theme glycosylation 551:563 arg1 mechanism 509:517 the mechanism 505:517 the mechanism of attenuation 505:532 The results suggest that the mechanism of attenuation is a lack of NS1 glycosylation, which blocks efficient replication, maturation, and NS1 secretion from the endoplasmic reticulum and results in changes to the virus-induced ultrastructure. 25392222 3 7 from reticulum 653:661 arg1 maturation 602:611 maturation 602:611 maturation 602:611 The results suggest that the mechanism of attenuation is a lack of NS1 glycosylation, which blocks efficient replication, maturation, and NS1 secretion from the endoplasmic reticulum and results in changes to the virus-induced ultrastructure. 25392222 3 7 from reticulum 653:661 arg1 replication 589:599 efficient replication 579:599 efficient replication 579:599 The results suggest that the mechanism of attenuation is a lack of NS1 glycosylation, which blocks efficient replication, maturation, and NS1 secretion from the endoplasmic reticulum and results in changes to the virus-induced ultrastructure. 25392222 3 7 from reticulum 653:661 arg1 secretion 622:630 NS1 secretion 618:630 NS1 secretion 618:630 The results suggest that the mechanism of attenuation is a lack of NS1 glycosylation, which blocks efficient replication, maturation, and NS1 secretion from the endoplasmic reticulum and results in changes to the virus-induced ultrastructure. 25392222 1 8 gly glycosylation 224:236 arg2 sites 238:242 the three N-linked glycosylation sites 205:242 the three N-linked glycosylation sites 205:242 We have previously shown that ablation of the three N-linked glycosylation sites in the West Nile virus NS1 protein completely attenuates mouse neuroinvasiveness (≥1,000,000 PFU). 25392222 1 8 gly glycosylation 224:236 arg2 three 209:213 three 209:213 three 209:213 We have previously shown that ablation of the three N-linked glycosylation sites in the West Nile virus NS1 protein completely attenuates mouse neuroinvasiveness (≥1,000,000 PFU). 25392222 2 9 theme NY99 439:442 arg1 strain 444:449 the parental NY99 strain 426:449 the parental NY99 strain in monkey kidney Vero cells 426:477 Here, we compared the replication of the NS1130-132QQA/175A/207A mutant to that of the parental NY99 strain in monkey kidney Vero cells. 25392222 2 10 theme kidney 461:466 arg1 cells 473:477 monkey kidney Vero cells 454:477 monkey kidney Vero cells 454:477 Here, we compared the replication of the NS1130-132QQA/175A/207A mutant to that of the parental NY99 strain in monkey kidney Vero cells. 25392222 0 11 theme West 11:14 arg1 virus 21:25 Attenuated West Nile virus 0:25 Attenuated West Nile virus mutant NS1130-132QQA/175A/207A 0:56 Attenuated West Nile virus mutant NS1130-132QQA/175A/207A exhibits virus-induced ultrastructural changes and accumulation of protein in the endoplasmic reticulum. 25392222 0 12 theme Attenuated 0:9 arg1 virus 21:25 Attenuated West Nile virus 0:25 Attenuated West Nile virus mutant NS1130-132QQA/175A/207A 0:56 Attenuated West Nile virus mutant NS1130-132QQA/175A/207A exhibits virus-induced ultrastructural changes and accumulation of protein in the endoplasmic reticulum. 25392222 1 13 theme mouse 301:305 arg1 neuroinvasiveness 307:323 mouse neuroinvasiveness 301:323 mouse neuroinvasiveness (≥1,000,000 PFU) 301:340 We have previously shown that ablation of the three N-linked glycosylation sites in the West Nile virus NS1 protein completely attenuates mouse neuroinvasiveness (≥1,000,000 PFU). 25392222 1 13 theme mouse 301:305 arg1 PFU 337:339 ≥1,000,000 PFU 326:339 ≥1,000,000 PFU 326:339 We have previously shown that ablation of the three N-linked glycosylation sites in the West Nile virus NS1 protein completely attenuates mouse neuroinvasiveness (≥1,000,000 PFU). 25392222 3 14 theme efficient 579:587 arg1 replication 589:599 efficient replication 579:599 efficient replication 579:599 The results suggest that the mechanism of attenuation is a lack of NS1 glycosylation, which blocks efficient replication, maturation, and NS1 secretion from the endoplasmic reticulum and results in changes to the virus-induced ultrastructure. 25392222 2 15 theme mutant 408:413 arg1 replication 365:375 the replication 361:375 the replication of the NS1130-132QQA/175A/207A mutant to that of the parental NY99 strain in monkey kidney Vero cells 361:477 Here, we compared the replication of the NS1130-132QQA/175A/207A mutant to that of the parental NY99 strain in monkey kidney Vero cells. 25392222 0 16 theme virus 21:25 arg1 NS1130-132QQA/175A/207A 34:56 Attenuated West Nile virus mutant NS1130-132QQA/175A/207A 0:56 Attenuated West Nile virus mutant NS1130-132QQA/175A/207A 0:56 Attenuated West Nile virus mutant NS1130-132QQA/175A/207A exhibits virus-induced ultrastructural changes and accumulation of protein in the endoplasmic reticulum. 25392222 1 17 theme N-linked 215:222 arg1 sites 238:242 the three N-linked glycosylation sites 205:242 the three N-linked glycosylation sites 205:242 We have previously shown that ablation of the three N-linked glycosylation sites in the West Nile virus NS1 protein completely attenuates mouse neuroinvasiveness (≥1,000,000 PFU). 25392222 0 18 theme Nile 16:19 arg1 virus 21:25 Attenuated West Nile virus 0:25 Attenuated West Nile virus mutant NS1130-132QQA/175A/207A 0:56 Attenuated West Nile virus mutant NS1130-132QQA/175A/207A exhibits virus-induced ultrastructural changes and accumulation of protein in the endoplasmic reticulum. 25392222 0 19 theme endoplasmic 140:150 arg1 reticulum 152:160 the endoplasmic reticulum 136:160 the endoplasmic reticulum 136:160 Attenuated West Nile virus mutant NS1130-132QQA/175A/207A exhibits virus-induced ultrastructural changes and accumulation of protein in the endoplasmic reticulum. 25392222 0 20 from accumulation 109:120 arg1 reticulum 152:160 the endoplasmic reticulum 136:160 the endoplasmic reticulum 136:160 Attenuated West Nile virus mutant NS1130-132QQA/175A/207A exhibits virus-induced ultrastructural changes and accumulation of protein in the endoplasmic reticulum. 25392222 1 21 theme glycosylation 224:236 arg1 sites 238:242 the three N-linked glycosylation sites 205:242 the three N-linked glycosylation sites 205:242 We have previously shown that ablation of the three N-linked glycosylation sites in the West Nile virus NS1 protein completely attenuates mouse neuroinvasiveness (≥1,000,000 PFU). 25392222 2 22 theme parental 430:437 arg1 strain 444:449 the parental NY99 strain 426:449 the parental NY99 strain in monkey kidney Vero cells 426:477 Here, we compared the replication of the NS1130-132QQA/175A/207A mutant to that of the parental NY99 strain in monkey kidney Vero cells. 25392222 1 23 theme sites 238:242 arg1 ablation 193:200 ablation 193:200 ablation of the three N-linked glycosylation sites in the West Nile virus NS1 protein 193:277 We have previously shown that ablation of the three N-linked glycosylation sites in the West Nile virus NS1 protein completely attenuates mouse neuroinvasiveness (≥1,000,000 PFU). 25392222 0 24 theme mutant 27:32 arg1 NS1130-132QQA/175A/207A 34:56 Attenuated West Nile virus mutant NS1130-132QQA/175A/207A 0:56 Attenuated West Nile virus mutant NS1130-132QQA/175A/207A 0:56 Attenuated West Nile virus mutant NS1130-132QQA/175A/207A exhibits virus-induced ultrastructural changes and accumulation of protein in the endoplasmic reticulum. 25392222 0 25 from changes 97:103 arg1 reticulum 152:160 the endoplasmic reticulum 136:160 the endoplasmic reticulum 136:160 Attenuated West Nile virus mutant NS1130-132QQA/175A/207A exhibits virus-induced ultrastructural changes and accumulation of protein in the endoplasmic reticulum. 25392222 2 26 theme monkey 454:459 arg1 cells 473:477 monkey kidney Vero cells 454:477 monkey kidney Vero cells 454:477 Here, we compared the replication of the NS1130-132QQA/175A/207A mutant to that of the parental NY99 strain in monkey kidney Vero cells. 25392222 0 27 theme virus-induced 67:79 arg1 changes 97:103 virus-induced ultrastructural changes 67:103 virus-induced ultrastructural changes 67:103 Attenuated West Nile virus mutant NS1130-132QQA/175A/207A exhibits virus-induced ultrastructural changes and accumulation of protein in the endoplasmic reticulum. 25392222 3 28 theme endoplasmic 641:651 arg1 reticulum 653:661 the endoplasmic reticulum 637:661 the endoplasmic reticulum 637:661 The results suggest that the mechanism of attenuation is a lack of NS1 glycosylation, which blocks efficient replication, maturation, and NS1 secretion from the endoplasmic reticulum and results in changes to the virus-induced ultrastructure. 25392222 2 29 from strain 444:449 arg1 cells 473:477 monkey kidney Vero cells 454:477 monkey kidney Vero cells 454:477 Here, we compared the replication of the NS1130-132QQA/175A/207A mutant to that of the parental NY99 strain in monkey kidney Vero cells. 25392222 1 30 theme West 251:254 arg1 virus 261:265 the West Nile virus 247:265 the West Nile virus NS1 protein 247:277 We have previously shown that ablation of the three N-linked glycosylation sites in the West Nile virus NS1 protein completely attenuates mouse neuroinvasiveness (≥1,000,000 PFU). 25392222 2 31 theme NS1130-132QQA/175A/207A 384:406 arg1 mutant 408:413 the NS1130-132QQA/175A/207A mutant 380:413 the NS1130-132QQA/175A/207A mutant 380:413 Here, we compared the replication of the NS1130-132QQA/175A/207A mutant to that of the parental NY99 strain in monkey kidney Vero cells. 25392222 1 32 theme Nile 256:259 arg1 virus 261:265 the West Nile virus 247:265 the West Nile virus NS1 protein 247:277 We have previously shown that ablation of the three N-linked glycosylation sites in the West Nile virus NS1 protein completely attenuates mouse neuroinvasiveness (≥1,000,000 PFU). 25392222 0 33 theme ultrastructural 81:95 arg1 changes 97:103 virus-induced ultrastructural changes 67:103 virus-induced ultrastructural changes 67:103 Attenuated West Nile virus mutant NS1130-132QQA/175A/207A exhibits virus-induced ultrastructural changes and accumulation of protein in the endoplasmic reticulum. 25392222 3 34 theme NS1 618:620 arg1 secretion 622:630 NS1 secretion 618:630 NS1 secretion 618:630 The results suggest that the mechanism of attenuation is a lack of NS1 glycosylation, which blocks efficient replication, maturation, and NS1 secretion from the endoplasmic reticulum and results in changes to the virus-induced ultrastructure. 25392222 1 35 from ablation 193:200 arg1 protein 271:277 the West Nile virus NS1 protein 247:277 the West Nile virus NS1 protein 247:277 We have previously shown that ablation of the three N-linked glycosylation sites in the West Nile virus NS1 protein completely attenuates mouse neuroinvasiveness (≥1,000,000 PFU). 25392222 2 36 theme Vero 468:471 arg1 cells 473:477 monkey kidney Vero cells 454:477 monkey kidney Vero cells 454:477 Here, we compared the replication of the NS1130-132QQA/175A/207A mutant to that of the parental NY99 strain in monkey kidney Vero cells. 25392222 1 37 theme virus 261:265 arg1 protein 271:277 the West Nile virus NS1 protein 247:277 the West Nile virus NS1 protein 247:277 We have previously shown that ablation of the three N-linked glycosylation sites in the West Nile virus NS1 protein completely attenuates mouse neuroinvasiveness (≥1,000,000 PFU). 27546384 0 0 theme sperm 66:70 arg1 functions 72:80 sperm functions 66:80 sperm functions 66:80 The human sperm proteome 2.0: An integrated resource for studying sperm functions at the level of posttranslational modification. 27546384 5 1 theme different 779:787 arg1 distributions 800:812 different functional distributions 779:812 different functional distributions 779:812 Functional enrichment analyses showed that different types of modified sperm proteins displayed different functional distributions. 27546384 8 2 theme glycosylated 1159:1170 arg1 proteins 1172:1179 glycosylated proteins 1159:1179 glycosylated proteins 1159:1179 Thus, it is efficient to search for fertility-associated biomarkers in acetylated, phosphorylated, and glycosylated proteins. 27546384 2 3 theme enrichment 325:334 arg1 methods 336:342 enrichment methods 325:342 enrichment methods 325:342 However, most large-scale proteomic studies only focused on a single type of modification due to the limitation of enrichment methods. 27546384 5 4 theme functional 789:798 arg1 distributions 800:812 different functional distributions 779:812 different functional distributions 779:812 Functional enrichment analyses showed that different types of modified sperm proteins displayed different functional distributions. 27546384 9 5 theme same 1236:1239 arg1 proteins 1241:1248 the same proteins 1232:1248 the same proteins 1232:1248 We also predicted modification cross-talks within the same proteins or between different proteins that provided potential hotspot targets for understanding the regulation of sperm functions via multiple modifications. 27546384 1 6 theme PTMs 147:150 arg1 types 138:142 Various types 130:142 Various types of PTMs 130:150 Various types of PTMs play important roles in the regulation of sperm proteins. 27546384 9 7 theme multiple 1376:1383 arg1 modifications 1385:1397 multiple modifications 1376:1397 multiple modifications 1376:1397 We also predicted modification cross-talks within the same proteins or between different proteins that provided potential hotspot targets for understanding the regulation of sperm functions via multiple modifications. 27546384 3 8 theme N-terminal 542:551 arg1 proteins 564:571 protein N-terminal acetylated proteins 534:571 protein N-terminal acetylated proteins 534:571 To investigate the complex composition of modified sperm proteins, we constructed the human sperm proteome 2.0 that integrated lysine acetylated, phosphorylated, N-linked glycosylated, and protein N-terminal acetylated proteins from previously published proteomic datasets. 27546384 3 9 theme acetylated 553:562 arg1 proteins 564:571 protein N-terminal acetylated proteins 534:571 protein N-terminal acetylated proteins 534:571 To investigate the complex composition of modified sperm proteins, we constructed the human sperm proteome 2.0 that integrated lysine acetylated, phosphorylated, N-linked glycosylated, and protein N-terminal acetylated proteins from previously published proteomic datasets. 27546384 9 10 dep modification 1200:1211 arg1 cross-talks 1213:1223 cross-talks 1213:1223 cross-talks 1213:1223 We also predicted modification cross-talks within the same proteins or between different proteins that provided potential hotspot targets for understanding the regulation of sperm functions via multiple modifications. 27546384 6 11 gly glycosylated 861:872 arg1 proteins 874:881 glycosylated proteins 861:881 glycosylated proteins 861:881 We found that acetylated, phosphorylated, and glycosylated proteins are more directly involved in sperm functions. 27546384 5 12 theme modified 745:752 arg1 proteins 760:767 modified sperm proteins 745:767 modified sperm proteins 745:767 Functional enrichment analyses showed that different types of modified sperm proteins displayed different functional distributions. 27546384 4 13 from proteins 658:665 arg1 total 621:625 A total 619:625 A total of 6069 modified sites on 2132 proteins 619:665 A total of 6069 modified sites on 2132 proteins were annotated. 27546384 4 14 theme 2132 653:656 arg1 proteins 658:665 2132 proteins 653:665 2132 proteins 653:665 A total of 6069 modified sites on 2132 proteins were annotated. 27546384 5 15 theme sperm 754:758 arg1 proteins 760:767 modified sperm proteins 745:767 modified sperm proteins 745:767 Functional enrichment analyses showed that different types of modified sperm proteins displayed different functional distributions. 27546384 6 16 theme sperm 913:917 arg1 functions 919:927 sperm functions 913:927 sperm functions 913:927 We found that acetylated, phosphorylated, and glycosylated proteins are more directly involved in sperm functions. 27546384 9 17 theme different 1261:1269 arg1 proteins 1271:1278 different proteins 1261:1278 different proteins that provided potential hotspot targets for understanding the regulation of sperm functions via multiple modifications 1261:1397 We also predicted modification cross-talks within the same proteins or between different proteins that provided potential hotspot targets for understanding the regulation of sperm functions via multiple modifications. 27546384 1 18 theme important 157:165 arg1 roles 167:171 important roles 157:171 important roles 157:171 Various types of PTMs play important roles in the regulation of sperm proteins. 27546384 0 19 theme human 4:8 arg1 sperm 10:14 The human sperm 0:14 The human sperm 0:14 The human sperm proteome 2.0: An integrated resource for studying sperm functions at the level of posttranslational modification. 27546384 4 20 theme modified 635:642 arg1 sites 644:648 6069 modified sites 630:648 6069 modified sites on 2132 proteins 630:665 A total of 6069 modified sites on 2132 proteins were annotated. 27546384 5 21 theme proteins 760:767 arg1 types 736:740 different types 726:740 different types of modified sperm proteins 726:767 Functional enrichment analyses showed that different types of modified sperm proteins displayed different functional distributions. 27546384 2 22 theme modification 287:298 arg1 type 279:282 a single type 270:282 a single type of modification due to the limitation of enrichment methods 270:342 However, most large-scale proteomic studies only focused on a single type of modification due to the limitation of enrichment methods. 27546384 3 23 theme proteins 402:409 arg1 composition 372:382 the complex composition 360:382 the complex composition of modified sperm proteins 360:409 To investigate the complex composition of modified sperm proteins, we constructed the human sperm proteome 2.0 that integrated lysine acetylated, phosphorylated, N-linked glycosylated, and protein N-terminal acetylated proteins from previously published proteomic datasets. 27546384 3 24 theme complex 364:370 arg1 composition 372:382 the complex composition 360:382 the complex composition of modified sperm proteins 360:409 To investigate the complex composition of modified sperm proteins, we constructed the human sperm proteome 2.0 that integrated lysine acetylated, phosphorylated, N-linked glycosylated, and protein N-terminal acetylated proteins from previously published proteomic datasets. 27546384 8 25 theme fertility-associated 1092:1111 arg1 biomarkers 1113:1122 fertility-associated biomarkers 1092:1122 fertility-associated biomarkers in acetylated, phosphorylated, and glycosylated proteins 1092:1179 Thus, it is efficient to search for fertility-associated biomarkers in acetylated, phosphorylated, and glycosylated proteins. 27546384 4 26 from sites 644:648 arg1 proteins 658:665 2132 proteins 653:665 2132 proteins 653:665 A total of 6069 modified sites on 2132 proteins were annotated. 27546384 0 27 theme posttranslational 98:114 arg1 modification 116:127 posttranslational modification 98:127 posttranslational modification 98:127 The human sperm proteome 2.0: An integrated resource for studying sperm functions at the level of posttranslational modification. 27546384 7 28 theme nonmodified 971:981 arg1 proteins 983:990 nonmodified proteins 971:990 nonmodified proteins 971:990 While N-termnial acetylated proteins and nonmodified proteins appear to be more associated with the basic cellular functions. 27546384 3 29 theme protein 534:540 arg1 proteins 564:571 protein N-terminal acetylated proteins 534:571 protein N-terminal acetylated proteins 534:571 To investigate the complex composition of modified sperm proteins, we constructed the human sperm proteome 2.0 that integrated lysine acetylated, phosphorylated, N-linked glycosylated, and protein N-terminal acetylated proteins from previously published proteomic datasets. 27546384 3 30 theme sperm 437:441 arg1 proteome 443:450 the human sperm proteome 2.0 427:454 the human sperm proteome 2.0 that integrated lysine acetylated, phosphorylated, N-linked glycosylated, and protein N-terminal acetylated proteins from previously published proteomic datasets 427:616 To investigate the complex composition of modified sperm proteins, we constructed the human sperm proteome 2.0 that integrated lysine acetylated, phosphorylated, N-linked glycosylated, and protein N-terminal acetylated proteins from previously published proteomic datasets. 27546384 9 31 theme potential 1294:1302 arg1 targets 1312:1318 potential hotspot targets 1294:1318 potential hotspot targets for understanding the regulation of sperm functions via multiple modifications 1294:1397 We also predicted modification cross-talks within the same proteins or between different proteins that provided potential hotspot targets for understanding the regulation of sperm functions via multiple modifications. 27546384 2 32 theme single 272:277 arg1 type 279:282 a single type 270:282 a single type of modification due to the limitation of enrichment methods 270:342 However, most large-scale proteomic studies only focused on a single type of modification due to the limitation of enrichment methods. 27546384 8 33 gly glycosylated 1159:1170 arg1 proteins 1172:1179 glycosylated proteins 1159:1179 glycosylated proteins 1159:1179 Thus, it is efficient to search for fertility-associated biomarkers in acetylated, phosphorylated, and glycosylated proteins. 27546384 3 34 theme modified 387:394 arg1 proteins 402:409 modified sperm proteins 387:409 modified sperm proteins 387:409 To investigate the complex composition of modified sperm proteins, we constructed the human sperm proteome 2.0 that integrated lysine acetylated, phosphorylated, N-linked glycosylated, and protein N-terminal acetylated proteins from previously published proteomic datasets. 27546384 9 35 theme hotspot 1304:1310 arg1 targets 1312:1318 potential hotspot targets 1294:1318 potential hotspot targets for understanding the regulation of sperm functions via multiple modifications 1294:1397 We also predicted modification cross-talks within the same proteins or between different proteins that provided potential hotspot targets for understanding the regulation of sperm functions via multiple modifications. 27546384 3 36 theme published 589:597 arg1 datasets 609:616 previously published proteomic datasets 578:616 previously published proteomic datasets 578:616 To investigate the complex composition of modified sperm proteins, we constructed the human sperm proteome 2.0 that integrated lysine acetylated, phosphorylated, N-linked glycosylated, and protein N-terminal acetylated proteins from previously published proteomic datasets. 27546384 4 37 theme sites 644:648 arg1 total 621:625 A total 619:625 A total of 6069 modified sites on 2132 proteins 619:665 A total of 6069 modified sites on 2132 proteins were annotated. 27546384 3 38 theme sperm 396:400 arg1 proteins 402:409 modified sperm proteins 387:409 modified sperm proteins 387:409 To investigate the complex composition of modified sperm proteins, we constructed the human sperm proteome 2.0 that integrated lysine acetylated, phosphorylated, N-linked glycosylated, and protein N-terminal acetylated proteins from previously published proteomic datasets. 27546384 8 39 from biomarkers 1113:1122 arg1 phosphorylated 1139:1152 phosphorylated 1139:1152 phosphorylated 1139:1152 Thus, it is efficient to search for fertility-associated biomarkers in acetylated, phosphorylated, and glycosylated proteins. 27546384 8 39 from biomarkers 1113:1122 arg1 acetylated 1127:1136 acetylated 1127:1136 acetylated 1127:1136 Thus, it is efficient to search for fertility-associated biomarkers in acetylated, phosphorylated, and glycosylated proteins. 27546384 8 39 from biomarkers 1113:1122 arg1 proteins 1172:1179 glycosylated proteins 1159:1179 glycosylated proteins 1159:1179 Thus, it is efficient to search for fertility-associated biomarkers in acetylated, phosphorylated, and glycosylated proteins. 27546384 0 40 theme modification 116:127 arg1 level 89:93 the level 85:93 the level of posttranslational modification 85:127 The human sperm proteome 2.0: An integrated resource for studying sperm functions at the level of posttranslational modification. 27546384 3 41 theme proteomic 599:607 arg1 datasets 609:616 previously published proteomic datasets 578:616 previously published proteomic datasets 578:616 To investigate the complex composition of modified sperm proteins, we constructed the human sperm proteome 2.0 that integrated lysine acetylated, phosphorylated, N-linked glycosylated, and protein N-terminal acetylated proteins from previously published proteomic datasets. 27546384 1 42 theme sperm 194:198 arg1 proteins 200:207 sperm proteins 194:207 sperm proteins 194:207 Various types of PTMs play important roles in the regulation of sperm proteins. 27546384 0 43 theme integrated 33:42 arg1 resource 44:51 An integrated resource 30:51 An integrated resource for studying sperm functions at the level of posttranslational modification 30:127 The human sperm proteome 2.0: An integrated resource for studying sperm functions at the level of posttranslational modification. 27546384 3 44 theme integrated 461:470 arg1 lysine 472:477 integrated lysine 461:477 integrated lysine 461:477 To investigate the complex composition of modified sperm proteins, we constructed the human sperm proteome 2.0 that integrated lysine acetylated, phosphorylated, N-linked glycosylated, and protein N-terminal acetylated proteins from previously published proteomic datasets. 27546384 5 45 theme different 726:734 arg1 types 736:740 different types 726:740 different types of modified sperm proteins 726:767 Functional enrichment analyses showed that different types of modified sperm proteins displayed different functional distributions. 27546384 9 46 theme functions 1362:1370 arg1 regulation 1342:1351 the regulation 1338:1351 the regulation of sperm functions 1338:1370 We also predicted modification cross-talks within the same proteins or between different proteins that provided potential hotspot targets for understanding the regulation of sperm functions via multiple modifications. 27546384 3 47 dep glycosylated 516:527 arg1 N-linked 507:514 N-linked 507:514 N-linked 507:514 To investigate the complex composition of modified sperm proteins, we constructed the human sperm proteome 2.0 that integrated lysine acetylated, phosphorylated, N-linked glycosylated, and protein N-terminal acetylated proteins from previously published proteomic datasets. 27546384 7 48 theme acetylated 947:956 arg1 proteins 958:965 N-termnial acetylated proteins 936:965 N-termnial acetylated proteins 936:965 While N-termnial acetylated proteins and nonmodified proteins appear to be more associated with the basic cellular functions. 27546384 5 49 theme Functional 683:692 arg1 analyses 705:712 Functional enrichment analyses 683:712 Functional enrichment analyses 683:712 Functional enrichment analyses showed that different types of modified sperm proteins displayed different functional distributions. 27546384 6 50 theme glycosylated 861:872 arg1 proteins 874:881 glycosylated proteins 861:881 glycosylated proteins 861:881 We found that acetylated, phosphorylated, and glycosylated proteins are more directly involved in sperm functions. 27546384 1 51 theme proteins 200:207 arg1 regulation 180:189 the regulation 176:189 the regulation of sperm proteins 176:207 Various types of PTMs play important roles in the regulation of sperm proteins. 27546384 5 52 theme enrichment 694:703 arg1 analyses 705:712 Functional enrichment analyses 683:712 Functional enrichment analyses 683:712 Functional enrichment analyses showed that different types of modified sperm proteins displayed different functional distributions. 27546384 2 53 theme proteomic 236:244 arg1 studies 246:252 most large-scale proteomic studies 219:252 most large-scale proteomic studies 219:252 However, most large-scale proteomic studies only focused on a single type of modification due to the limitation of enrichment methods. 27546384 7 54 theme basic 1030:1034 arg1 functions 1045:1053 the basic cellular functions 1026:1053 the basic cellular functions 1026:1053 While N-termnial acetylated proteins and nonmodified proteins appear to be more associated with the basic cellular functions. 27546384 4 55 from total 621:625 arg1 proteins 658:665 2132 proteins 653:665 2132 proteins 653:665 A total of 6069 modified sites on 2132 proteins were annotated. 27546384 3 56 theme human 431:435 arg1 proteome 443:450 the human sperm proteome 2.0 427:454 the human sperm proteome 2.0 that integrated lysine acetylated, phosphorylated, N-linked glycosylated, and protein N-terminal acetylated proteins from previously published proteomic datasets 427:616 To investigate the complex composition of modified sperm proteins, we constructed the human sperm proteome 2.0 that integrated lysine acetylated, phosphorylated, N-linked glycosylated, and protein N-terminal acetylated proteins from previously published proteomic datasets. 27546384 2 57 theme large-scale 224:234 arg1 studies 246:252 most large-scale proteomic studies 219:252 most large-scale proteomic studies 219:252 However, most large-scale proteomic studies only focused on a single type of modification due to the limitation of enrichment methods. 27546384 7 58 theme cellular 1036:1043 arg1 functions 1045:1053 the basic cellular functions 1026:1053 the basic cellular functions 1026:1053 While N-termnial acetylated proteins and nonmodified proteins appear to be more associated with the basic cellular functions. 27546384 1 59 theme Various 130:136 arg1 types 138:142 Various types 130:142 Various types of PTMs 130:150 Various types of PTMs play important roles in the regulation of sperm proteins. 27546384 7 60 theme N-termnial 936:945 arg1 proteins 958:965 N-termnial acetylated proteins 936:965 N-termnial acetylated proteins 936:965 While N-termnial acetylated proteins and nonmodified proteins appear to be more associated with the basic cellular functions. 27546384 9 61 theme sperm 1356:1360 arg1 functions 1362:1370 sperm functions 1356:1370 sperm functions 1356:1370 We also predicted modification cross-talks within the same proteins or between different proteins that provided potential hotspot targets for understanding the regulation of sperm functions via multiple modifications. 27546384 2 62 theme most 219:222 arg1 studies 246:252 most large-scale proteomic studies 219:252 most large-scale proteomic studies 219:252 However, most large-scale proteomic studies only focused on a single type of modification due to the limitation of enrichment methods. 27546384 2 63 theme methods 336:342 arg1 limitation 311:320 the limitation 307:320 the limitation of enrichment methods 307:342 However, most large-scale proteomic studies only focused on a single type of modification due to the limitation of enrichment methods. 25611677 4 0 theme Fe3O4 908:912 arg1 nanoparticles 919:931 Fe3O4@SiO2 nanoparticles 908:931 Fe3O4@SiO2 nanoparticles 908:931 Herein, a novel affinity material was synthesized to improve the binding capacity and detection sensitivity for glycopeptides by coating a poly(2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide (PMSA) shell onto Fe3O4@SiO2 nanoparticles, taking advantage of reflux-precipitation polymerization for the first time (denoted as Fe3O4@SiO2@PMSA). 25611677 7 1 from detection 1748:1756 arg1 samples 1831:1837 biological samples 1820:1837 biological samples 1820:1837 Furthermore, in the analysis of real complicated biological samples, 905 unique N-glycosylation sites from 458 N-glycosylated proteins were reliably identified in three replicate analyses of a 65 μg protein sample extracted from mouse liver, showing the great potential of Fe3O4@SiO2@PMSA in the detection and identification of low-abundance N-linked glycopeptides in biological samples. 25611677 6 2 theme rapid 1425:1429 arg1 separation 1440:1449 rapid magnetic separation 1425:1449 rapid magnetic separation 1425:1449 The resulting Fe3O4@SiO2@PMSA demonstrated an outstanding ability for glycopeptide enrichment with high selectivity, extremely high detection sensitivity (0.1 fmol), large binding capacity (100 mg g(-1)), high enrichment recovery (above 73.6%) and rapid magnetic separation. 25611677 4 3 theme SiO2 914:917 arg1 nanoparticles 919:931 Fe3O4@SiO2 nanoparticles 908:931 Fe3O4@SiO2 nanoparticles 908:931 Herein, a novel affinity material was synthesized to improve the binding capacity and detection sensitivity for glycopeptides by coating a poly(2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide (PMSA) shell onto Fe3O4@SiO2 nanoparticles, taking advantage of reflux-precipitation polymerization for the first time (denoted as Fe3O4@SiO2@PMSA). 25611677 7 4 gly N-glycosylation 1532:1546 arg2 905 1521:1523 905 1521:1523 905 1521:1523 Furthermore, in the analysis of real complicated biological samples, 905 unique N-glycosylation sites from 458 N-glycosylated proteins were reliably identified in three replicate analyses of a 65 μg protein sample extracted from mouse liver, showing the great potential of Fe3O4@SiO2@PMSA in the detection and identification of low-abundance N-linked glycopeptides in biological samples. 25611677 7 4 gly N-glycosylation 1532:1546 arg2 sites 1548:1552 905 unique N-glycosylation sites 1521:1552 905 unique N-glycosylation sites from 458 N-glycosylated proteins 1521:1585 Furthermore, in the analysis of real complicated biological samples, 905 unique N-glycosylation sites from 458 N-glycosylated proteins were reliably identified in three replicate analyses of a 65 μg protein sample extracted from mouse liver, showing the great potential of Fe3O4@SiO2@PMSA in the detection and identification of low-abundance N-linked glycopeptides in biological samples. 25611677 6 5 theme high 1304:1307 arg1 sensitivity 1319:1329 extremely high detection sensitivity 1294:1329 extremely high detection sensitivity (0.1 fmol) 1294:1340 The resulting Fe3O4@SiO2@PMSA demonstrated an outstanding ability for glycopeptide enrichment with high selectivity, extremely high detection sensitivity (0.1 fmol), large binding capacity (100 mg g(-1)), high enrichment recovery (above 73.6%) and rapid magnetic separation. 25611677 6 5 theme high 1304:1307 arg1 fmol 1336:1339 0.1 fmol 1332:1339 0.1 fmol 1332:1339 The resulting Fe3O4@SiO2@PMSA demonstrated an outstanding ability for glycopeptide enrichment with high selectivity, extremely high detection sensitivity (0.1 fmol), large binding capacity (100 mg g(-1)), high enrichment recovery (above 73.6%) and rapid magnetic separation. 25611677 1 6 theme biomarkers 303:312 arg1 discovery 282:290 the discovery 278:290 the discovery of disease biomarkers in biological systems 278:334 Highly selective and efficient capture of glycosylated proteins and peptides from complex biological samples is of profound significance for the discovery of disease biomarkers in biological systems. 25611677 6 7 theme SiO2 1197:1200 arg1 PMSA 1202:1205 The resulting Fe3O4@SiO2@PMSA 1177:1205 The resulting Fe3O4@SiO2@PMSA 1177:1205 The resulting Fe3O4@SiO2@PMSA demonstrated an outstanding ability for glycopeptide enrichment with high selectivity, extremely high detection sensitivity (0.1 fmol), large binding capacity (100 mg g(-1)), high enrichment recovery (above 73.6%) and rapid magnetic separation. 25611677 6 8 gly glycopeptide 1247:1258 arg2 glycopeptide 1247:1258 glycopeptide enrichment 1247:1269 glycopeptide enrichment with high selectivity 1247:1291 The resulting Fe3O4@SiO2@PMSA demonstrated an outstanding ability for glycopeptide enrichment with high selectivity, extremely high detection sensitivity (0.1 fmol), large binding capacity (100 mg g(-1)), high enrichment recovery (above 73.6%) and rapid magnetic separation. 25611677 1 9 theme peptides 205:212 arg1 capture 168:174 Highly selective and efficient capture 137:174 Highly selective and efficient capture of glycosylated proteins and peptides from complex biological samples 137:244 Highly selective and efficient capture of glycosylated proteins and peptides from complex biological samples is of profound significance for the discovery of disease biomarkers in biological systems. 25611677 7 10 gly N-glycosylated 1563:1576 arg1 proteins 1578:1585 458 N-glycosylated proteins 1559:1585 458 N-glycosylated proteins 1559:1585 Furthermore, in the analysis of real complicated biological samples, 905 unique N-glycosylation sites from 458 N-glycosylated proteins were reliably identified in three replicate analyses of a 65 μg protein sample extracted from mouse liver, showing the great potential of Fe3O4@SiO2@PMSA in the detection and identification of low-abundance N-linked glycopeptides in biological samples. 25611677 6 11 theme Fe3O4 1191:1195 arg1 PMSA 1202:1205 The resulting Fe3O4@SiO2@PMSA 1177:1205 The resulting Fe3O4@SiO2@PMSA 1177:1205 The resulting Fe3O4@SiO2@PMSA demonstrated an outstanding ability for glycopeptide enrichment with high selectivity, extremely high detection sensitivity (0.1 fmol), large binding capacity (100 mg g(-1)), high enrichment recovery (above 73.6%) and rapid magnetic separation. 25611677 6 12 theme high 1276:1279 arg1 selectivity 1281:1291 high selectivity 1276:1291 high selectivity 1276:1291 The resulting Fe3O4@SiO2@PMSA demonstrated an outstanding ability for glycopeptide enrichment with high selectivity, extremely high detection sensitivity (0.1 fmol), large binding capacity (100 mg g(-1)), high enrichment recovery (above 73.6%) and rapid magnetic separation. 25611677 2 13 theme hydrophilic 347:357 arg1 HILIC 394:398 HILIC 394:398 HILIC 394:398 Recently, hydrophilic interaction liquid chromatography (HILIC)-based functional materials have been extensively utilized for glycopeptide enrichment. 25611677 2 13 theme hydrophilic 347:357 arg1 chromatography 378:391 hydrophilic interaction liquid chromatography 347:391 hydrophilic interaction liquid chromatography (HILIC)-based functional materials 347:426 Recently, hydrophilic interaction liquid chromatography (HILIC)-based functional materials have been extensively utilized for glycopeptide enrichment. 25611677 1 14 theme complex 219:225 arg1 samples 238:244 complex biological samples 219:244 complex biological samples 219:244 Highly selective and efficient capture of glycosylated proteins and peptides from complex biological samples is of profound significance for the discovery of disease biomarkers in biological systems. 25611677 4 15 theme reflux-precipitation 954:973 arg1 polymerization 975:988 reflux-precipitation polymerization 954:988 reflux-precipitation polymerization 954:988 Herein, a novel affinity material was synthesized to improve the binding capacity and detection sensitivity for glycopeptides by coating a poly(2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide (PMSA) shell onto Fe3O4@SiO2 nanoparticles, taking advantage of reflux-precipitation polymerization for the first time (denoted as Fe3O4@SiO2@PMSA). 25611677 7 16 theme SiO2 1731:1734 arg1 PMSA 1736:1739 Fe3O4@SiO2@PMSA 1725:1739 Fe3O4@SiO2@PMSA 1725:1739 Furthermore, in the analysis of real complicated biological samples, 905 unique N-glycosylation sites from 458 N-glycosylated proteins were reliably identified in three replicate analyses of a 65 μg protein sample extracted from mouse liver, showing the great potential of Fe3O4@SiO2@PMSA in the detection and identification of low-abundance N-linked glycopeptides in biological samples. 25611677 3 17 gly glycopeptides 661:673 arg2 glycopeptides 661:673 glycopeptides 661:673 glycopeptides 661:673 However, the low amount of immobilized hydrophilic groups on the affinity material has limited its specificity, detection sensitivity and binding capacity in the capture of glycopeptides. 25611677 3 18 theme binding 626:632 arg1 capacity 634:641 binding capacity 626:641 binding capacity 626:641 However, the low amount of immobilized hydrophilic groups on the affinity material has limited its specificity, detection sensitivity and binding capacity in the capture of glycopeptides. 25611677 6 19 theme large 1343:1347 arg1 g 1374:1374 100 mg g(-1) 1367:1378 100 mg g(-1) 1367:1378 The resulting Fe3O4@SiO2@PMSA demonstrated an outstanding ability for glycopeptide enrichment with high selectivity, extremely high detection sensitivity (0.1 fmol), large binding capacity (100 mg g(-1)), high enrichment recovery (above 73.6%) and rapid magnetic separation. 25611677 6 19 theme large 1343:1347 arg1 capacity 1357:1364 large binding capacity 1343:1364 large binding capacity (100 mg g(-1)) 1343:1379 The resulting Fe3O4@SiO2@PMSA demonstrated an outstanding ability for glycopeptide enrichment with high selectivity, extremely high detection sensitivity (0.1 fmol), large binding capacity (100 mg g(-1)), high enrichment recovery (above 73.6%) and rapid magnetic separation. 25611677 5 20 theme hydrophilic 1103:1113 arg1 property 1115:1122 excellent hydrophilic property 1093:1122 excellent hydrophilic property 1093:1122 The thick polymer shell endows the nanoparticles with excellent hydrophilic property and several functional groups on the polymer chains. 25611677 3 21 theme glycopeptides 661:673 arg1 capture 650:656 the capture 646:656 the capture of glycopeptides 646:673 However, the low amount of immobilized hydrophilic groups on the affinity material has limited its specificity, detection sensitivity and binding capacity in the capture of glycopeptides. 25611677 6 22 theme glycopeptide 1247:1258 arg1 enrichment 1260:1269 glycopeptide enrichment 1247:1269 glycopeptide enrichment with high selectivity 1247:1291 The resulting Fe3O4@SiO2@PMSA demonstrated an outstanding ability for glycopeptide enrichment with high selectivity, extremely high detection sensitivity (0.1 fmol), large binding capacity (100 mg g(-1)), high enrichment recovery (above 73.6%) and rapid magnetic separation. 25611677 1 23 theme selective 144:152 arg1 capture 168:174 Highly selective and efficient capture 137:174 Highly selective and efficient capture of glycosylated proteins and peptides from complex biological samples 137:244 Highly selective and efficient capture of glycosylated proteins and peptides from complex biological samples is of profound significance for the discovery of disease biomarkers in biological systems. 25611677 7 24 gly glycopeptides 1803:1815 arg2 glycopeptides 1803:1815 low-abundance N-linked glycopeptides 1780:1815 low-abundance N-linked glycopeptides 1780:1815 Furthermore, in the analysis of real complicated biological samples, 905 unique N-glycosylation sites from 458 N-glycosylated proteins were reliably identified in three replicate analyses of a 65 μg protein sample extracted from mouse liver, showing the great potential of Fe3O4@SiO2@PMSA in the detection and identification of low-abundance N-linked glycopeptides in biological samples. 25611677 1 25 gly glycosylated 179:190 arg1 proteins 192:199 glycosylated proteins 179:199 glycosylated proteins 179:199 Highly selective and efficient capture of glycosylated proteins and peptides from complex biological samples is of profound significance for the discovery of disease biomarkers in biological systems. 25611677 1 26 theme efficient 158:166 arg1 capture 168:174 Highly selective and efficient capture 137:174 Highly selective and efficient capture of glycosylated proteins and peptides from complex biological samples 137:244 Highly selective and efficient capture of glycosylated proteins and peptides from complex biological samples is of profound significance for the discovery of disease biomarkers in biological systems. 25611677 7 27 theme great 1706:1710 arg1 potential 1712:1720 the great potential 1702:1720 the great potential of Fe3O4@SiO2@PMSA in the detection and identification of low-abundance N-linked glycopeptides in biological samples 1702:1837 Furthermore, in the analysis of real complicated biological samples, 905 unique N-glycosylation sites from 458 N-glycosylated proteins were reliably identified in three replicate analyses of a 65 μg protein sample extracted from mouse liver, showing the great potential of Fe3O4@SiO2@PMSA in the detection and identification of low-abundance N-linked glycopeptides in biological samples. 25611677 5 28 from nanoparticles 1074:1086 arg1 chains 1169:1174 the polymer chains 1157:1174 the polymer chains 1157:1174 The thick polymer shell endows the nanoparticles with excellent hydrophilic property and several functional groups on the polymer chains. 25611677 6 29 with enrichment 1260:1269 arg1 selectivity 1281:1291 high selectivity 1276:1291 high selectivity 1276:1291 The resulting Fe3O4@SiO2@PMSA demonstrated an outstanding ability for glycopeptide enrichment with high selectivity, extremely high detection sensitivity (0.1 fmol), large binding capacity (100 mg g(-1)), high enrichment recovery (above 73.6%) and rapid magnetic separation. 25611677 4 30 theme @ 1026:1026 arg1 PMSA 1032:1035 Fe3O4@SiO2@PMSA 1021:1035 Fe3O4@SiO2@PMSA 1021:1035 Herein, a novel affinity material was synthesized to improve the binding capacity and detection sensitivity for glycopeptides by coating a poly(2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide (PMSA) shell onto Fe3O4@SiO2 nanoparticles, taking advantage of reflux-precipitation polymerization for the first time (denoted as Fe3O4@SiO2@PMSA). 25611677 2 31 used utilized 450:457 arg2 materials 418:426 hydrophilic interaction liquid chromatography (HILIC)-based functional materials 347:426 hydrophilic interaction liquid chromatography (HILIC)-based functional materials 347:426 Recently, hydrophilic interaction liquid chromatography (HILIC)-based functional materials have been extensively utilized for glycopeptide enrichment. 25611677 4 32 theme detection 762:770 arg1 sensitivity 772:782 detection sensitivity 762:782 detection sensitivity 762:782 Herein, a novel affinity material was synthesized to improve the binding capacity and detection sensitivity for glycopeptides by coating a poly(2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide (PMSA) shell onto Fe3O4@SiO2 nanoparticles, taking advantage of reflux-precipitation polymerization for the first time (denoted as Fe3O4@SiO2@PMSA). 25611677 0 33 theme specific 93:100 arg1 capture 102:108 highly specific capture 86:108 highly specific capture of N-linked glycopeptides 86:134 Facile synthesis of zwitterionic polymer-coated core-shell magnetic nanoparticles for highly specific capture of N-linked glycopeptides. 25611677 5 34 theme polymer 1161:1167 arg1 chains 1169:1174 the polymer chains 1157:1174 the polymer chains 1157:1174 The thick polymer shell endows the nanoparticles with excellent hydrophilic property and several functional groups on the polymer chains. 25611677 1 35 theme proteins 192:199 arg1 capture 168:174 Highly selective and efficient capture 137:174 Highly selective and efficient capture of glycosylated proteins and peptides from complex biological samples 137:244 Highly selective and efficient capture of glycosylated proteins and peptides from complex biological samples is of profound significance for the discovery of disease biomarkers in biological systems. 25611677 4 36 theme first 998:1002 arg1 time 1004:1007 the first time 994:1007 the first time (denoted as Fe3O4@SiO2@PMSA) 994:1036 Herein, a novel affinity material was synthesized to improve the binding capacity and detection sensitivity for glycopeptides by coating a poly(2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide (PMSA) shell onto Fe3O4@SiO2 nanoparticles, taking advantage of reflux-precipitation polymerization for the first time (denoted as Fe3O4@SiO2@PMSA). 25611677 7 37 theme unique 1525:1530 arg1 sites 1548:1552 905 unique N-glycosylation sites 1521:1552 905 unique N-glycosylation sites from 458 N-glycosylated proteins 1521:1585 Furthermore, in the analysis of real complicated biological samples, 905 unique N-glycosylation sites from 458 N-glycosylated proteins were reliably identified in three replicate analyses of a 65 μg protein sample extracted from mouse liver, showing the great potential of Fe3O4@SiO2@PMSA in the detection and identification of low-abundance N-linked glycopeptides in biological samples. 25611677 5 38 with nanoparticles 1074:1086 arg1 groups 1147:1152 several functional groups 1128:1152 several functional groups 1128:1152 The thick polymer shell endows the nanoparticles with excellent hydrophilic property and several functional groups on the polymer chains. 25611677 5 38 with nanoparticles 1074:1086 arg1 property 1115:1122 excellent hydrophilic property 1093:1122 excellent hydrophilic property 1093:1122 The thick polymer shell endows the nanoparticles with excellent hydrophilic property and several functional groups on the polymer chains. 25611677 0 39 theme glycopeptides 122:134 arg1 capture 102:108 highly specific capture 86:108 highly specific capture of N-linked glycopeptides 86:134 Facile synthesis of zwitterionic polymer-coated core-shell magnetic nanoparticles for highly specific capture of N-linked glycopeptides. 25611677 5 40 theme functional 1136:1145 arg1 groups 1147:1152 several functional groups 1128:1152 several functional groups 1128:1152 The thick polymer shell endows the nanoparticles with excellent hydrophilic property and several functional groups on the polymer chains. 25611677 7 41 theme sample 1659:1664 arg1 analyses 1631:1638 three replicate analyses 1615:1638 three replicate analyses of a 65 μg protein sample extracted from mouse liver 1615:1691 Furthermore, in the analysis of real complicated biological samples, 905 unique N-glycosylation sites from 458 N-glycosylated proteins were reliably identified in three replicate analyses of a 65 μg protein sample extracted from mouse liver, showing the great potential of Fe3O4@SiO2@PMSA in the detection and identification of low-abundance N-linked glycopeptides in biological samples. 25611677 0 42 theme Facile 0:5 arg1 synthesis 7:15 Facile synthesis 0:15 Facile synthesis of zwitterionic polymer-coated core-shell magnetic nanoparticles for highly specific capture of N-linked glycopeptides. 0:135 Facile synthesis of zwitterionic polymer-coated core-shell magnetic nanoparticles for highly specific capture of N-linked glycopeptides. 25611677 7 43 theme μg 1648:1649 arg1 sample 1659:1664 a 65 μg protein sample 1643:1664 a 65 μg protein sample extracted from mouse liver 1643:1691 Furthermore, in the analysis of real complicated biological samples, 905 unique N-glycosylation sites from 458 N-glycosylated proteins were reliably identified in three replicate analyses of a 65 μg protein sample extracted from mouse liver, showing the great potential of Fe3O4@SiO2@PMSA in the detection and identification of low-abundance N-linked glycopeptides in biological samples. 25611677 3 44 theme immobilized 515:525 arg1 groups 539:544 immobilized hydrophilic groups 515:544 immobilized hydrophilic groups 515:544 However, the low amount of immobilized hydrophilic groups on the affinity material has limited its specificity, detection sensitivity and binding capacity in the capture of glycopeptides. 25611677 7 45 theme samples 1512:1518 arg1 analysis 1472:1479 the analysis 1468:1479 the analysis of real complicated biological samples 1468:1518 Furthermore, in the analysis of real complicated biological samples, 905 unique N-glycosylation sites from 458 N-glycosylated proteins were reliably identified in three replicate analyses of a 65 μg protein sample extracted from mouse liver, showing the great potential of Fe3O4@SiO2@PMSA in the detection and identification of low-abundance N-linked glycopeptides in biological samples. 25611677 4 46 theme @ 1031:1031 arg1 PMSA 1032:1035 Fe3O4@SiO2@PMSA 1021:1035 Fe3O4@SiO2@PMSA 1021:1035 Herein, a novel affinity material was synthesized to improve the binding capacity and detection sensitivity for glycopeptides by coating a poly(2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide (PMSA) shell onto Fe3O4@SiO2 nanoparticles, taking advantage of reflux-precipitation polymerization for the first time (denoted as Fe3O4@SiO2@PMSA). 25611677 2 47 theme glycopeptide 463:474 arg1 enrichment 476:485 glycopeptide enrichment 463:485 glycopeptide enrichment 463:485 Recently, hydrophilic interaction liquid chromatography (HILIC)-based functional materials have been extensively utilized for glycopeptide enrichment. 25611677 0 48 theme polymer-coated 33:46 arg1 nanoparticles 68:80 zwitterionic polymer-coated core-shell magnetic nanoparticles 20:80 zwitterionic polymer-coated core-shell magnetic nanoparticles 20:80 Facile synthesis of zwitterionic polymer-coated core-shell magnetic nanoparticles for highly specific capture of N-linked glycopeptides. 25611677 7 49 theme complicated 1489:1499 arg1 samples 1512:1518 real complicated biological samples 1484:1518 real complicated biological samples 1484:1518 Furthermore, in the analysis of real complicated biological samples, 905 unique N-glycosylation sites from 458 N-glycosylated proteins were reliably identified in three replicate analyses of a 65 μg protein sample extracted from mouse liver, showing the great potential of Fe3O4@SiO2@PMSA in the detection and identification of low-abundance N-linked glycopeptides in biological samples. 25611677 7 50 theme biological 1820:1829 arg1 samples 1831:1837 biological samples 1820:1837 biological samples 1820:1837 Furthermore, in the analysis of real complicated biological samples, 905 unique N-glycosylation sites from 458 N-glycosylated proteins were reliably identified in three replicate analyses of a 65 μg protein sample extracted from mouse liver, showing the great potential of Fe3O4@SiO2@PMSA in the detection and identification of low-abundance N-linked glycopeptides in biological samples. 25611677 4 51 theme hydroxide 880:888 arg1 shell 897:901 a poly(2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide (PMSA) shell 813:901 a poly(2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide (PMSA) shell onto Fe3O4@SiO2 nanoparticles 813:931 Herein, a novel affinity material was synthesized to improve the binding capacity and detection sensitivity for glycopeptides by coating a poly(2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide (PMSA) shell onto Fe3O4@SiO2 nanoparticles, taking advantage of reflux-precipitation polymerization for the first time (denoted as Fe3O4@SiO2@PMSA). 25611677 0 52 theme magnetic 59:66 arg1 nanoparticles 68:80 zwitterionic polymer-coated core-shell magnetic nanoparticles 20:80 zwitterionic polymer-coated core-shell magnetic nanoparticles 20:80 Facile synthesis of zwitterionic polymer-coated core-shell magnetic nanoparticles for highly specific capture of N-linked glycopeptides. 25611677 5 53 theme polymer 1049:1055 arg1 shell 1057:1061 The thick polymer shell 1039:1061 The thick polymer shell 1039:1061 The thick polymer shell endows the nanoparticles with excellent hydrophilic property and several functional groups on the polymer chains. 25611677 7 54 theme glycopeptides 1803:1815 arg1 identification 1762:1775 identification 1762:1775 identification 1762:1775 Furthermore, in the analysis of real complicated biological samples, 905 unique N-glycosylation sites from 458 N-glycosylated proteins were reliably identified in three replicate analyses of a 65 μg protein sample extracted from mouse liver, showing the great potential of Fe3O4@SiO2@PMSA in the detection and identification of low-abundance N-linked glycopeptides in biological samples. 25611677 7 54 theme glycopeptides 1803:1815 arg1 detection 1748:1756 detection 1748:1756 detection 1748:1756 Furthermore, in the analysis of real complicated biological samples, 905 unique N-glycosylation sites from 458 N-glycosylated proteins were reliably identified in three replicate analyses of a 65 μg protein sample extracted from mouse liver, showing the great potential of Fe3O4@SiO2@PMSA in the detection and identification of low-abundance N-linked glycopeptides in biological samples. 25611677 2 55 theme chromatography 378:391 arg1 materials 418:426 hydrophilic interaction liquid chromatography (HILIC)-based functional materials 347:426 hydrophilic interaction liquid chromatography (HILIC)-based functional materials 347:426 Recently, hydrophilic interaction liquid chromatography (HILIC)-based functional materials have been extensively utilized for glycopeptide enrichment. 25611677 1 56 theme profound 252:259 arg1 significance 261:272 profound significance 252:272 profound significance for the discovery of disease biomarkers in biological systems 252:334 Highly selective and efficient capture of glycosylated proteins and peptides from complex biological samples is of profound significance for the discovery of disease biomarkers in biological systems. 25611677 7 57 from proteins 1578:1585 arg1 sites 1548:1552 905 unique N-glycosylation sites 1521:1552 905 unique N-glycosylation sites from 458 N-glycosylated proteins 1521:1585 Furthermore, in the analysis of real complicated biological samples, 905 unique N-glycosylation sites from 458 N-glycosylated proteins were reliably identified in three replicate analyses of a 65 μg protein sample extracted from mouse liver, showing the great potential of Fe3O4@SiO2@PMSA in the detection and identification of low-abundance N-linked glycopeptides in biological samples. 25611677 7 58 dep detection 1748:1756 arg1 the 1744:1746 the 1744:1746 the 1744:1746 Furthermore, in the analysis of real complicated biological samples, 905 unique N-glycosylation sites from 458 N-glycosylated proteins were reliably identified in three replicate analyses of a 65 μg protein sample extracted from mouse liver, showing the great potential of Fe3O4@SiO2@PMSA in the detection and identification of low-abundance N-linked glycopeptides in biological samples. 25611677 6 59 theme enrichment 1387:1396 arg1 recovery 1398:1405 high enrichment recovery 1382:1405 high enrichment recovery (above 73.6%) 1382:1419 The resulting Fe3O4@SiO2@PMSA demonstrated an outstanding ability for glycopeptide enrichment with high selectivity, extremely high detection sensitivity (0.1 fmol), large binding capacity (100 mg g(-1)), high enrichment recovery (above 73.6%) and rapid magnetic separation. 25611677 6 59 theme enrichment 1387:1396 arg1 % 1418:1418 above 73.6% 1408:1418 above 73.6% 1408:1418 The resulting Fe3O4@SiO2@PMSA demonstrated an outstanding ability for glycopeptide enrichment with high selectivity, extremely high detection sensitivity (0.1 fmol), large binding capacity (100 mg g(-1)), high enrichment recovery (above 73.6%) and rapid magnetic separation. 25611677 0 60 link N-linked 113:120 arg1 glycopeptides 122:134 N-linked glycopeptides 113:134 N-linked glycopeptides 113:134 Facile synthesis of zwitterionic polymer-coated core-shell magnetic nanoparticles for highly specific capture of N-linked glycopeptides. 25611677 2 61 theme -based 400:405 arg1 materials 418:426 hydrophilic interaction liquid chromatography (HILIC)-based functional materials 347:426 hydrophilic interaction liquid chromatography (HILIC)-based functional materials 347:426 Recently, hydrophilic interaction liquid chromatography (HILIC)-based functional materials have been extensively utilized for glycopeptide enrichment. 25611677 6 62 theme magnetic 1431:1438 arg1 separation 1440:1449 rapid magnetic separation 1425:1449 rapid magnetic separation 1425:1449 The resulting Fe3O4@SiO2@PMSA demonstrated an outstanding ability for glycopeptide enrichment with high selectivity, extremely high detection sensitivity (0.1 fmol), large binding capacity (100 mg g(-1)), high enrichment recovery (above 73.6%) and rapid magnetic separation. 25611677 7 63 theme PMSA 1736:1739 arg1 potential 1712:1720 the great potential 1702:1720 the great potential of Fe3O4@SiO2@PMSA in the detection and identification of low-abundance N-linked glycopeptides in biological samples 1702:1837 Furthermore, in the analysis of real complicated biological samples, 905 unique N-glycosylation sites from 458 N-glycosylated proteins were reliably identified in three replicate analyses of a 65 μg protein sample extracted from mouse liver, showing the great potential of Fe3O4@SiO2@PMSA in the detection and identification of low-abundance N-linked glycopeptides in biological samples. 25611677 6 64 theme detection 1309:1317 arg1 sensitivity 1319:1329 extremely high detection sensitivity 1294:1329 extremely high detection sensitivity (0.1 fmol) 1294:1340 The resulting Fe3O4@SiO2@PMSA demonstrated an outstanding ability for glycopeptide enrichment with high selectivity, extremely high detection sensitivity (0.1 fmol), large binding capacity (100 mg g(-1)), high enrichment recovery (above 73.6%) and rapid magnetic separation. 25611677 6 64 theme detection 1309:1317 arg1 fmol 1336:1339 0.1 fmol 1332:1339 0.1 fmol 1332:1339 The resulting Fe3O4@SiO2@PMSA demonstrated an outstanding ability for glycopeptide enrichment with high selectivity, extremely high detection sensitivity (0.1 fmol), large binding capacity (100 mg g(-1)), high enrichment recovery (above 73.6%) and rapid magnetic separation. 25611677 3 65 theme detection 600:608 arg1 sensitivity 610:620 detection sensitivity 600:620 detection sensitivity 600:620 However, the low amount of immobilized hydrophilic groups on the affinity material has limited its specificity, detection sensitivity and binding capacity in the capture of glycopeptides. 25611677 1 66 theme disease 295:301 arg1 biomarkers 303:312 disease biomarkers 295:312 disease biomarkers 295:312 Highly selective and efficient capture of glycosylated proteins and peptides from complex biological samples is of profound significance for the discovery of disease biomarkers in biological systems. 25611677 4 67 theme @ 913:913 arg1 nanoparticles 919:931 Fe3O4@SiO2 nanoparticles 908:931 Fe3O4@SiO2 nanoparticles 908:931 Herein, a novel affinity material was synthesized to improve the binding capacity and detection sensitivity for glycopeptides by coating a poly(2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide (PMSA) shell onto Fe3O4@SiO2 nanoparticles, taking advantage of reflux-precipitation polymerization for the first time (denoted as Fe3O4@SiO2@PMSA). 25611677 6 68 theme @ 1201:1201 arg1 PMSA 1202:1205 The resulting Fe3O4@SiO2@PMSA 1177:1205 The resulting Fe3O4@SiO2@PMSA 1177:1205 The resulting Fe3O4@SiO2@PMSA demonstrated an outstanding ability for glycopeptide enrichment with high selectivity, extremely high detection sensitivity (0.1 fmol), large binding capacity (100 mg g(-1)), high enrichment recovery (above 73.6%) and rapid magnetic separation. 25611677 6 69 theme high 1382:1385 arg1 recovery 1398:1405 high enrichment recovery 1382:1405 high enrichment recovery (above 73.6%) 1382:1419 The resulting Fe3O4@SiO2@PMSA demonstrated an outstanding ability for glycopeptide enrichment with high selectivity, extremely high detection sensitivity (0.1 fmol), large binding capacity (100 mg g(-1)), high enrichment recovery (above 73.6%) and rapid magnetic separation. 25611677 6 69 theme high 1382:1385 arg1 % 1418:1418 above 73.6% 1408:1418 above 73.6% 1408:1418 The resulting Fe3O4@SiO2@PMSA demonstrated an outstanding ability for glycopeptide enrichment with high selectivity, extremely high detection sensitivity (0.1 fmol), large binding capacity (100 mg g(-1)), high enrichment recovery (above 73.6%) and rapid magnetic separation. 25611677 7 70 theme @ 1735:1735 arg1 PMSA 1736:1739 Fe3O4@SiO2@PMSA 1725:1739 Fe3O4@SiO2@PMSA 1725:1739 Furthermore, in the analysis of real complicated biological samples, 905 unique N-glycosylation sites from 458 N-glycosylated proteins were reliably identified in three replicate analyses of a 65 μg protein sample extracted from mouse liver, showing the great potential of Fe3O4@SiO2@PMSA in the detection and identification of low-abundance N-linked glycopeptides in biological samples. 25611677 6 71 theme @ 1196:1196 arg1 PMSA 1202:1205 The resulting Fe3O4@SiO2@PMSA 1177:1205 The resulting Fe3O4@SiO2@PMSA 1177:1205 The resulting Fe3O4@SiO2@PMSA demonstrated an outstanding ability for glycopeptide enrichment with high selectivity, extremely high detection sensitivity (0.1 fmol), large binding capacity (100 mg g(-1)), high enrichment recovery (above 73.6%) and rapid magnetic separation. 25611677 2 72 theme interaction 359:369 arg1 HILIC 394:398 HILIC 394:398 HILIC 394:398 Recently, hydrophilic interaction liquid chromatography (HILIC)-based functional materials have been extensively utilized for glycopeptide enrichment. 25611677 2 72 theme interaction 359:369 arg1 chromatography 378:391 hydrophilic interaction liquid chromatography 347:391 hydrophilic interaction liquid chromatography (HILIC)-based functional materials 347:426 Recently, hydrophilic interaction liquid chromatography (HILIC)-based functional materials have been extensively utilized for glycopeptide enrichment. 25611677 7 73 dep analyses 1631:1638 arg1 replicate 1621:1629 replicate 1621:1629 replicate 1621:1629 Furthermore, in the analysis of real complicated biological samples, 905 unique N-glycosylation sites from 458 N-glycosylated proteins were reliably identified in three replicate analyses of a 65 μg protein sample extracted from mouse liver, showing the great potential of Fe3O4@SiO2@PMSA in the detection and identification of low-abundance N-linked glycopeptides in biological samples. 25611677 7 74 theme @ 1730:1730 arg1 PMSA 1736:1739 Fe3O4@SiO2@PMSA 1725:1739 Fe3O4@SiO2@PMSA 1725:1739 Furthermore, in the analysis of real complicated biological samples, 905 unique N-glycosylation sites from 458 N-glycosylated proteins were reliably identified in three replicate analyses of a 65 μg protein sample extracted from mouse liver, showing the great potential of Fe3O4@SiO2@PMSA in the detection and identification of low-abundance N-linked glycopeptides in biological samples. 25611677 6 75 theme resulting 1181:1189 arg1 PMSA 1202:1205 The resulting Fe3O4@SiO2@PMSA 1177:1205 The resulting Fe3O4@SiO2@PMSA 1177:1205 The resulting Fe3O4@SiO2@PMSA demonstrated an outstanding ability for glycopeptide enrichment with high selectivity, extremely high detection sensitivity (0.1 fmol), large binding capacity (100 mg g(-1)), high enrichment recovery (above 73.6%) and rapid magnetic separation. 25611677 1 76 theme biological 227:236 arg1 samples 238:244 complex biological samples 219:244 complex biological samples 219:244 Highly selective and efficient capture of glycosylated proteins and peptides from complex biological samples is of profound significance for the discovery of disease biomarkers in biological systems. 25611677 7 77 from potential 1712:1720 arg1 identification 1762:1775 identification 1762:1775 identification 1762:1775 Furthermore, in the analysis of real complicated biological samples, 905 unique N-glycosylation sites from 458 N-glycosylated proteins were reliably identified in three replicate analyses of a 65 μg protein sample extracted from mouse liver, showing the great potential of Fe3O4@SiO2@PMSA in the detection and identification of low-abundance N-linked glycopeptides in biological samples. 25611677 7 77 from potential 1712:1720 arg1 detection 1748:1756 detection 1748:1756 detection 1748:1756 Furthermore, in the analysis of real complicated biological samples, 905 unique N-glycosylation sites from 458 N-glycosylated proteins were reliably identified in three replicate analyses of a 65 μg protein sample extracted from mouse liver, showing the great potential of Fe3O4@SiO2@PMSA in the detection and identification of low-abundance N-linked glycopeptides in biological samples. 25611677 4 78 theme novel 686:690 arg1 material 701:708 a novel affinity material 684:708 a novel affinity material 684:708 Herein, a novel affinity material was synthesized to improve the binding capacity and detection sensitivity for glycopeptides by coating a poly(2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide (PMSA) shell onto Fe3O4@SiO2 nanoparticles, taking advantage of reflux-precipitation polymerization for the first time (denoted as Fe3O4@SiO2@PMSA). 25611677 4 79 gly glycopeptides 788:800 arg2 glycopeptides 788:800 glycopeptides 788:800 glycopeptides 788:800 Herein, a novel affinity material was synthesized to improve the binding capacity and detection sensitivity for glycopeptides by coating a poly(2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide (PMSA) shell onto Fe3O4@SiO2 nanoparticles, taking advantage of reflux-precipitation polymerization for the first time (denoted as Fe3O4@SiO2@PMSA). 25611677 5 80 theme excellent 1093:1101 arg1 property 1115:1122 excellent hydrophilic property 1093:1122 excellent hydrophilic property 1093:1122 The thick polymer shell endows the nanoparticles with excellent hydrophilic property and several functional groups on the polymer chains. 25611677 4 81 theme polymerization 975:988 arg1 advantage 941:949 advantage 941:949 advantage of reflux-precipitation polymerization 941:988 Herein, a novel affinity material was synthesized to improve the binding capacity and detection sensitivity for glycopeptides by coating a poly(2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide (PMSA) shell onto Fe3O4@SiO2 nanoparticles, taking advantage of reflux-precipitation polymerization for the first time (denoted as Fe3O4@SiO2@PMSA). 25611677 6 82 theme binding 1349:1355 arg1 g 1374:1374 100 mg g(-1) 1367:1378 100 mg g(-1) 1367:1378 The resulting Fe3O4@SiO2@PMSA demonstrated an outstanding ability for glycopeptide enrichment with high selectivity, extremely high detection sensitivity (0.1 fmol), large binding capacity (100 mg g(-1)), high enrichment recovery (above 73.6%) and rapid magnetic separation. 25611677 6 82 theme binding 1349:1355 arg1 capacity 1357:1364 large binding capacity 1343:1364 large binding capacity (100 mg g(-1)) 1343:1379 The resulting Fe3O4@SiO2@PMSA demonstrated an outstanding ability for glycopeptide enrichment with high selectivity, extremely high detection sensitivity (0.1 fmol), large binding capacity (100 mg g(-1)), high enrichment recovery (above 73.6%) and rapid magnetic separation. 25611677 1 83 from samples 238:244 arg1 capture 168:174 Highly selective and efficient capture 137:174 Highly selective and efficient capture of glycosylated proteins and peptides from complex biological samples 137:244 Highly selective and efficient capture of glycosylated proteins and peptides from complex biological samples is of profound significance for the discovery of disease biomarkers in biological systems. 25611677 7 84 theme Fe3O4 1725:1729 arg1 PMSA 1736:1739 Fe3O4@SiO2@PMSA 1725:1739 Fe3O4@SiO2@PMSA 1725:1739 Furthermore, in the analysis of real complicated biological samples, 905 unique N-glycosylation sites from 458 N-glycosylated proteins were reliably identified in three replicate analyses of a 65 μg protein sample extracted from mouse liver, showing the great potential of Fe3O4@SiO2@PMSA in the detection and identification of low-abundance N-linked glycopeptides in biological samples. 25611677 7 85 theme N-glycosylated 1563:1576 arg1 proteins 1578:1585 458 N-glycosylated proteins 1559:1585 458 N-glycosylated proteins 1559:1585 Furthermore, in the analysis of real complicated biological samples, 905 unique N-glycosylation sites from 458 N-glycosylated proteins were reliably identified in three replicate analyses of a 65 μg protein sample extracted from mouse liver, showing the great potential of Fe3O4@SiO2@PMSA in the detection and identification of low-abundance N-linked glycopeptides in biological samples. 25611677 6 86 theme outstanding 1223:1233 arg1 ability 1235:1241 an outstanding ability 1220:1241 an outstanding ability for glycopeptide enrichment with high selectivity 1220:1291 The resulting Fe3O4@SiO2@PMSA demonstrated an outstanding ability for glycopeptide enrichment with high selectivity, extremely high detection sensitivity (0.1 fmol), large binding capacity (100 mg g(-1)), high enrichment recovery (above 73.6%) and rapid magnetic separation. 25611677 3 87 theme groups 539:544 arg1 groups 539:544 immobilized hydrophilic groups 515:544 immobilized hydrophilic groups 515:544 However, the low amount of immobilized hydrophilic groups on the affinity material has limited its specificity, detection sensitivity and binding capacity in the capture of glycopeptides. 25611677 3 87 theme groups 539:544 arg1 amount 505:510 the low amount 497:510 the low amount of immobilized hydrophilic groups on the affinity material 497:569 However, the low amount of immobilized hydrophilic groups on the affinity material has limited its specificity, detection sensitivity and binding capacity in the capture of glycopeptides. 25611677 4 88 theme affinity 692:699 arg1 material 701:708 a novel affinity material 684:708 a novel affinity material 684:708 Herein, a novel affinity material was synthesized to improve the binding capacity and detection sensitivity for glycopeptides by coating a poly(2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide (PMSA) shell onto Fe3O4@SiO2 nanoparticles, taking advantage of reflux-precipitation polymerization for the first time (denoted as Fe3O4@SiO2@PMSA). 25611677 4 89 theme binding 741:747 arg1 capacity 749:756 the binding capacity 737:756 the binding capacity 737:756 Herein, a novel affinity material was synthesized to improve the binding capacity and detection sensitivity for glycopeptides by coating a poly(2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide (PMSA) shell onto Fe3O4@SiO2 nanoparticles, taking advantage of reflux-precipitation polymerization for the first time (denoted as Fe3O4@SiO2@PMSA). 25611677 1 90 theme glycosylated 179:190 arg1 proteins 192:199 glycosylated proteins 179:199 glycosylated proteins 179:199 Highly selective and efficient capture of glycosylated proteins and peptides from complex biological samples is of profound significance for the discovery of disease biomarkers in biological systems. 25611677 7 91 theme N-glycosylation 1532:1546 arg1 sites 1548:1552 905 unique N-glycosylation sites 1521:1552 905 unique N-glycosylation sites from 458 N-glycosylated proteins 1521:1585 Furthermore, in the analysis of real complicated biological samples, 905 unique N-glycosylation sites from 458 N-glycosylated proteins were reliably identified in three replicate analyses of a 65 μg protein sample extracted from mouse liver, showing the great potential of Fe3O4@SiO2@PMSA in the detection and identification of low-abundance N-linked glycopeptides in biological samples. 25611677 4 92 theme Fe3O4 1021:1025 arg1 PMSA 1032:1035 Fe3O4@SiO2@PMSA 1021:1035 Fe3O4@SiO2@PMSA 1021:1035 Herein, a novel affinity material was synthesized to improve the binding capacity and detection sensitivity for glycopeptides by coating a poly(2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide (PMSA) shell onto Fe3O4@SiO2 nanoparticles, taking advantage of reflux-precipitation polymerization for the first time (denoted as Fe3O4@SiO2@PMSA). 25611677 0 93 theme N-linked 113:120 arg1 glycopeptides 122:134 N-linked glycopeptides 113:134 N-linked glycopeptides 113:134 Facile synthesis of zwitterionic polymer-coated core-shell magnetic nanoparticles for highly specific capture of N-linked glycopeptides. 25611677 2 94 gly glycopeptide 463:474 arg2 glycopeptide 463:474 glycopeptide enrichment 463:485 glycopeptide enrichment 463:485 Recently, hydrophilic interaction liquid chromatography (HILIC)-based functional materials have been extensively utilized for glycopeptide enrichment. 25611677 6 95 theme mg 1371:1372 arg1 g 1374:1374 100 mg g(-1) 1367:1378 100 mg g(-1) 1367:1378 The resulting Fe3O4@SiO2@PMSA demonstrated an outstanding ability for glycopeptide enrichment with high selectivity, extremely high detection sensitivity (0.1 fmol), large binding capacity (100 mg g(-1)), high enrichment recovery (above 73.6%) and rapid magnetic separation. 25611677 6 95 theme mg 1371:1372 arg1 capacity 1357:1364 large binding capacity 1343:1364 large binding capacity (100 mg g(-1)) 1343:1379 The resulting Fe3O4@SiO2@PMSA demonstrated an outstanding ability for glycopeptide enrichment with high selectivity, extremely high detection sensitivity (0.1 fmol), large binding capacity (100 mg g(-1)), high enrichment recovery (above 73.6%) and rapid magnetic separation. 25611677 5 96 theme several 1128:1134 arg1 groups 1147:1152 several functional groups 1128:1152 several functional groups 1128:1152 The thick polymer shell endows the nanoparticles with excellent hydrophilic property and several functional groups on the polymer chains. 25611677 7 97 theme mouse 1681:1685 arg1 liver 1687:1691 mouse liver 1681:1691 mouse liver 1681:1691 Furthermore, in the analysis of real complicated biological samples, 905 unique N-glycosylation sites from 458 N-glycosylated proteins were reliably identified in three replicate analyses of a 65 μg protein sample extracted from mouse liver, showing the great potential of Fe3O4@SiO2@PMSA in the detection and identification of low-abundance N-linked glycopeptides in biological samples. 25611677 7 98 from identification 1762:1775 arg1 samples 1831:1837 biological samples 1820:1837 biological samples 1820:1837 Furthermore, in the analysis of real complicated biological samples, 905 unique N-glycosylation sites from 458 N-glycosylated proteins were reliably identified in three replicate analyses of a 65 μg protein sample extracted from mouse liver, showing the great potential of Fe3O4@SiO2@PMSA in the detection and identification of low-abundance N-linked glycopeptides in biological samples. 25611677 4 99 theme methacryloyloxy 823:837 arg1 poly 815:818 poly 815:818 a poly(2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide (PMSA) shell onto Fe3O4@SiO2 nanoparticles 813:931 Herein, a novel affinity material was synthesized to improve the binding capacity and detection sensitivity for glycopeptides by coating a poly(2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide (PMSA) shell onto Fe3O4@SiO2 nanoparticles, taking advantage of reflux-precipitation polymerization for the first time (denoted as Fe3O4@SiO2@PMSA). 25611677 4 99 theme methacryloyloxy 823:837 arg1 ethyl 839:843 2-(methacryloyloxy)ethyl 820:843 2-(methacryloyloxy)ethyl 820:843 Herein, a novel affinity material was synthesized to improve the binding capacity and detection sensitivity for glycopeptides by coating a poly(2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide (PMSA) shell onto Fe3O4@SiO2 nanoparticles, taking advantage of reflux-precipitation polymerization for the first time (denoted as Fe3O4@SiO2@PMSA). 25611677 3 100 theme low 501:503 arg1 groups 539:544 immobilized hydrophilic groups 515:544 immobilized hydrophilic groups 515:544 However, the low amount of immobilized hydrophilic groups on the affinity material has limited its specificity, detection sensitivity and binding capacity in the capture of glycopeptides. 25611677 3 100 theme low 501:503 arg1 amount 505:510 the low amount 497:510 the low amount of immobilized hydrophilic groups on the affinity material 497:569 However, the low amount of immobilized hydrophilic groups on the affinity material has limited its specificity, detection sensitivity and binding capacity in the capture of glycopeptides. 25611677 1 101 from discovery 282:290 arg1 systems 328:334 biological systems 317:334 biological systems 317:334 Highly selective and efficient capture of glycosylated proteins and peptides from complex biological samples is of profound significance for the discovery of disease biomarkers in biological systems. 25611677 0 102 theme zwitterionic 20:31 arg1 nanoparticles 68:80 zwitterionic polymer-coated core-shell magnetic nanoparticles 20:80 zwitterionic polymer-coated core-shell magnetic nanoparticles 20:80 Facile synthesis of zwitterionic polymer-coated core-shell magnetic nanoparticles for highly specific capture of N-linked glycopeptides. 25611677 1 103 theme biological 317:326 arg1 systems 328:334 biological systems 317:334 biological systems 317:334 Highly selective and efficient capture of glycosylated proteins and peptides from complex biological samples is of profound significance for the discovery of disease biomarkers in biological systems. 25611677 0 104 gly glycopeptides 122:134 arg2 glycopeptides 122:134 N-linked glycopeptides 113:134 N-linked glycopeptides 113:134 Facile synthesis of zwitterionic polymer-coated core-shell magnetic nanoparticles for highly specific capture of N-linked glycopeptides. 25611677 7 105 theme protein 1651:1657 arg1 sample 1659:1664 a 65 μg protein sample 1643:1664 a 65 μg protein sample extracted from mouse liver 1643:1691 Furthermore, in the analysis of real complicated biological samples, 905 unique N-glycosylation sites from 458 N-glycosylated proteins were reliably identified in three replicate analyses of a 65 μg protein sample extracted from mouse liver, showing the great potential of Fe3O4@SiO2@PMSA in the detection and identification of low-abundance N-linked glycopeptides in biological samples. 25611677 4 106 theme poly 815:818 arg1 PMSA 891:894 PMSA 891:894 PMSA 891:894 Herein, a novel affinity material was synthesized to improve the binding capacity and detection sensitivity for glycopeptides by coating a poly(2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide (PMSA) shell onto Fe3O4@SiO2 nanoparticles, taking advantage of reflux-precipitation polymerization for the first time (denoted as Fe3O4@SiO2@PMSA). 25611677 4 106 theme poly 815:818 arg1 hydroxide 880:888 a poly(2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide 813:888 a poly(2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide (PMSA) shell onto Fe3O4@SiO2 nanoparticles 813:931 Herein, a novel affinity material was synthesized to improve the binding capacity and detection sensitivity for glycopeptides by coating a poly(2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide (PMSA) shell onto Fe3O4@SiO2 nanoparticles, taking advantage of reflux-precipitation polymerization for the first time (denoted as Fe3O4@SiO2@PMSA). 25611677 3 107 theme hydrophilic 527:537 arg1 groups 539:544 immobilized hydrophilic groups 515:544 immobilized hydrophilic groups 515:544 However, the low amount of immobilized hydrophilic groups on the affinity material has limited its specificity, detection sensitivity and binding capacity in the capture of glycopeptides. 25611677 0 108 theme core-shell 48:57 arg1 nanoparticles 68:80 zwitterionic polymer-coated core-shell magnetic nanoparticles 20:80 zwitterionic polymer-coated core-shell magnetic nanoparticles 20:80 Facile synthesis of zwitterionic polymer-coated core-shell magnetic nanoparticles for highly specific capture of N-linked glycopeptides. 25611677 7 109 link N-linked 1794:1801 arg1 glycopeptides 1803:1815 low-abundance N-linked glycopeptides 1780:1815 low-abundance N-linked glycopeptides 1780:1815 Furthermore, in the analysis of real complicated biological samples, 905 unique N-glycosylation sites from 458 N-glycosylated proteins were reliably identified in three replicate analyses of a 65 μg protein sample extracted from mouse liver, showing the great potential of Fe3O4@SiO2@PMSA in the detection and identification of low-abundance N-linked glycopeptides in biological samples. 25611677 7 110 theme 65 1645:1646 arg1 μg 1648:1649 μg 1648:1649 μg 1648:1649 Furthermore, in the analysis of real complicated biological samples, 905 unique N-glycosylation sites from 458 N-glycosylated proteins were reliably identified in three replicate analyses of a 65 μg protein sample extracted from mouse liver, showing the great potential of Fe3O4@SiO2@PMSA in the detection and identification of low-abundance N-linked glycopeptides in biological samples. 25611677 4 111 theme SiO2 1027:1030 arg1 PMSA 1032:1035 Fe3O4@SiO2@PMSA 1021:1035 Fe3O4@SiO2@PMSA 1021:1035 Herein, a novel affinity material was synthesized to improve the binding capacity and detection sensitivity for glycopeptides by coating a poly(2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide (PMSA) shell onto Fe3O4@SiO2 nanoparticles, taking advantage of reflux-precipitation polymerization for the first time (denoted as Fe3O4@SiO2@PMSA). 25611677 4 112 theme 3-sulfopropyl 856:868 arg1 PMSA 891:894 PMSA 891:894 PMSA 891:894 Herein, a novel affinity material was synthesized to improve the binding capacity and detection sensitivity for glycopeptides by coating a poly(2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide (PMSA) shell onto Fe3O4@SiO2 nanoparticles, taking advantage of reflux-precipitation polymerization for the first time (denoted as Fe3O4@SiO2@PMSA). 25611677 4 112 theme 3-sulfopropyl 856:868 arg1 hydroxide 880:888 a poly(2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide 813:888 a poly(2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide (PMSA) shell onto Fe3O4@SiO2 nanoparticles 813:931 Herein, a novel affinity material was synthesized to improve the binding capacity and detection sensitivity for glycopeptides by coating a poly(2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide (PMSA) shell onto Fe3O4@SiO2 nanoparticles, taking advantage of reflux-precipitation polymerization for the first time (denoted as Fe3O4@SiO2@PMSA). 25611677 3 113 from amount 505:510 arg1 material 562:569 the affinity material 549:569 the affinity material 549:569 However, the low amount of immobilized hydrophilic groups on the affinity material has limited its specificity, detection sensitivity and binding capacity in the capture of glycopeptides. 25611677 0 114 theme nanoparticles 68:80 arg1 synthesis 7:15 Facile synthesis 0:15 Facile synthesis of zwitterionic polymer-coated core-shell magnetic nanoparticles for highly specific capture of N-linked glycopeptides. 0:135 Facile synthesis of zwitterionic polymer-coated core-shell magnetic nanoparticles for highly specific capture of N-linked glycopeptides. 25611677 7 115 theme biological 1501:1510 arg1 samples 1512:1518 real complicated biological samples 1484:1518 real complicated biological samples 1484:1518 Furthermore, in the analysis of real complicated biological samples, 905 unique N-glycosylation sites from 458 N-glycosylated proteins were reliably identified in three replicate analyses of a 65 μg protein sample extracted from mouse liver, showing the great potential of Fe3O4@SiO2@PMSA in the detection and identification of low-abundance N-linked glycopeptides in biological samples. 25611677 5 116 theme thick 1043:1047 arg1 shell 1057:1061 The thick polymer shell 1039:1061 The thick polymer shell 1039:1061 The thick polymer shell endows the nanoparticles with excellent hydrophilic property and several functional groups on the polymer chains. 25611677 4 117 theme ammonium 871:878 arg1 PMSA 891:894 PMSA 891:894 PMSA 891:894 Herein, a novel affinity material was synthesized to improve the binding capacity and detection sensitivity for glycopeptides by coating a poly(2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide (PMSA) shell onto Fe3O4@SiO2 nanoparticles, taking advantage of reflux-precipitation polymerization for the first time (denoted as Fe3O4@SiO2@PMSA). 25611677 4 117 theme ammonium 871:878 arg1 hydroxide 880:888 a poly(2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide 813:888 a poly(2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide (PMSA) shell onto Fe3O4@SiO2 nanoparticles 813:931 Herein, a novel affinity material was synthesized to improve the binding capacity and detection sensitivity for glycopeptides by coating a poly(2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide (PMSA) shell onto Fe3O4@SiO2 nanoparticles, taking advantage of reflux-precipitation polymerization for the first time (denoted as Fe3O4@SiO2@PMSA). 25611677 3 118 theme affinity 553:560 arg1 material 562:569 the affinity material 549:569 the affinity material 549:569 However, the low amount of immobilized hydrophilic groups on the affinity material has limited its specificity, detection sensitivity and binding capacity in the capture of glycopeptides. 25611677 7 119 theme real 1484:1487 arg1 samples 1512:1518 real complicated biological samples 1484:1518 real complicated biological samples 1484:1518 Furthermore, in the analysis of real complicated biological samples, 905 unique N-glycosylation sites from 458 N-glycosylated proteins were reliably identified in three replicate analyses of a 65 μg protein sample extracted from mouse liver, showing the great potential of Fe3O4@SiO2@PMSA in the detection and identification of low-abundance N-linked glycopeptides in biological samples. 25611677 2 120 theme liquid 371:376 arg1 HILIC 394:398 HILIC 394:398 HILIC 394:398 Recently, hydrophilic interaction liquid chromatography (HILIC)-based functional materials have been extensively utilized for glycopeptide enrichment. 25611677 2 120 theme liquid 371:376 arg1 chromatography 378:391 hydrophilic interaction liquid chromatography 347:391 hydrophilic interaction liquid chromatography (HILIC)-based functional materials 347:426 Recently, hydrophilic interaction liquid chromatography (HILIC)-based functional materials have been extensively utilized for glycopeptide enrichment. 25611677 7 121 theme N-linked 1794:1801 arg1 glycopeptides 1803:1815 low-abundance N-linked glycopeptides 1780:1815 low-abundance N-linked glycopeptides 1780:1815 Furthermore, in the analysis of real complicated biological samples, 905 unique N-glycosylation sites from 458 N-glycosylated proteins were reliably identified in three replicate analyses of a 65 μg protein sample extracted from mouse liver, showing the great potential of Fe3O4@SiO2@PMSA in the detection and identification of low-abundance N-linked glycopeptides in biological samples. 25611677 4 122 theme -dimethyl- 845:854 arg1 PMSA 891:894 PMSA 891:894 PMSA 891:894 Herein, a novel affinity material was synthesized to improve the binding capacity and detection sensitivity for glycopeptides by coating a poly(2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide (PMSA) shell onto Fe3O4@SiO2 nanoparticles, taking advantage of reflux-precipitation polymerization for the first time (denoted as Fe3O4@SiO2@PMSA). 25611677 4 122 theme -dimethyl- 845:854 arg1 hydroxide 880:888 a poly(2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide 813:888 a poly(2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide (PMSA) shell onto Fe3O4@SiO2 nanoparticles 813:931 Herein, a novel affinity material was synthesized to improve the binding capacity and detection sensitivity for glycopeptides by coating a poly(2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide (PMSA) shell onto Fe3O4@SiO2 nanoparticles, taking advantage of reflux-precipitation polymerization for the first time (denoted as Fe3O4@SiO2@PMSA). 25611677 2 123 theme functional 407:416 arg1 materials 418:426 hydrophilic interaction liquid chromatography (HILIC)-based functional materials 347:426 hydrophilic interaction liquid chromatography (HILIC)-based functional materials 347:426 Recently, hydrophilic interaction liquid chromatography (HILIC)-based functional materials have been extensively utilized for glycopeptide enrichment. 27599734 4 0 theme class 855:859 arg1 receptors 863:871 class 2 receptors 855:871 class 2 receptors 855:871 The characteristic structural features of IFNγR2 are concentrated in its N-terminal domain: an extensive π-cation motif of stacked residues KWRWRH, a NAG-W-NAG sandwich (where NAG stands for N-acetyl-D-glucosamine) and finally a helix formed by residues 78-85, which is unique among class 2 receptors. 27599734 6 1 dep revealed 1086:1093 arg1 identified 1203:1212 identified 1203:1212 identified putative binding sites for interferon-γ and receptor 1, the ligands of IFNγR2 1203:1290 Structure-based bioinformatic analysis revealed independent evolutionary behaviour of both receptor domains and, together with multiple sequence alignment, identified putative binding sites for interferon-γ and receptor 1, the ligands of IFNγR2. 27599734 3 2 theme class 508:512 arg1 receptors 516:524 other class 2 receptors 502:524 other class 2 receptors 502:524 Similar to other class 2 receptors, IFNγR2 has two fibronectin type III domains. 27599734 1 3 theme innate 258:263 arg1 immunity 278:285 innate and adaptive immunity 258:285 innate and adaptive immunity against viral and also bacterial and protozoal infections 258:343 Interferon-γ receptor 2 is a cell-surface receptor that is required for interferon-γ signalling and therefore plays a critical immunoregulatory role in innate and adaptive immunity against viral and also bacterial and protozoal infections. 27599734 4 4 theme stacked 695:701 arg1 sandwich 732:739 a NAG-W-NAG sandwich 720:739 a NAG-W-NAG sandwich (where NAG stands for N-acetyl-D-glucosamine) 720:785 The characteristic structural features of IFNγR2 are concentrated in its N-terminal domain: an extensive π-cation motif of stacked residues KWRWRH, a NAG-W-NAG sandwich (where NAG stands for N-acetyl-D-glucosamine) and finally a helix formed by residues 78-85, which is unique among class 2 receptors. 27599734 4 4 theme stacked 695:701 arg1 residues 703:710 stacked residues 695:710 stacked residues KWRWRH, a NAG-W-NAG sandwich (where NAG stands for N-acetyl-D-glucosamine) and finally a helix formed by residues 78-85 695:830 The characteristic structural features of IFNγR2 are concentrated in its N-terminal domain: an extensive π-cation motif of stacked residues KWRWRH, a NAG-W-NAG sandwich (where NAG stands for N-acetyl-D-glucosamine) and finally a helix formed by residues 78-85, which is unique among class 2 receptors. 27599734 4 4 theme stacked 695:701 arg1 KWRWRH 712:717 KWRWRH 712:717 KWRWRH 712:717 The characteristic structural features of IFNγR2 are concentrated in its N-terminal domain: an extensive π-cation motif of stacked residues KWRWRH, a NAG-W-NAG sandwich (where NAG stands for N-acetyl-D-glucosamine) and finally a helix formed by residues 78-85, which is unique among class 2 receptors. 27599734 4 4 theme stacked 695:701 arg1 helix 801:805 a helix 799:805 a helix 799:805 The characteristic structural features of IFNγR2 are concentrated in its N-terminal domain: an extensive π-cation motif of stacked residues KWRWRH, a NAG-W-NAG sandwich (where NAG stands for N-acetyl-D-glucosamine) and finally a helix formed by residues 78-85, which is unique among class 2 receptors. 27599734 4 5 dep residues 703:710 arg1 sandwich 732:739 a NAG-W-NAG sandwich 720:739 a NAG-W-NAG sandwich (where NAG stands for N-acetyl-D-glucosamine) 720:785 The characteristic structural features of IFNγR2 are concentrated in its N-terminal domain: an extensive π-cation motif of stacked residues KWRWRH, a NAG-W-NAG sandwich (where NAG stands for N-acetyl-D-glucosamine) and finally a helix formed by residues 78-85, which is unique among class 2 receptors. 27599734 4 5 dep residues 703:710 arg1 helix 801:805 a helix 799:805 a helix 799:805 The characteristic structural features of IFNγR2 are concentrated in its N-terminal domain: an extensive π-cation motif of stacked residues KWRWRH, a NAG-W-NAG sandwich (where NAG stands for N-acetyl-D-glucosamine) and finally a helix formed by residues 78-85, which is unique among class 2 receptors. 27599734 4 5 dep residues 703:710 arg1 residues 703:710 stacked residues 695:710 stacked residues KWRWRH, a NAG-W-NAG sandwich (where NAG stands for N-acetyl-D-glucosamine) and finally a helix formed by residues 78-85 695:830 The characteristic structural features of IFNγR2 are concentrated in its N-terminal domain: an extensive π-cation motif of stacked residues KWRWRH, a NAG-W-NAG sandwich (where NAG stands for N-acetyl-D-glucosamine) and finally a helix formed by residues 78-85, which is unique among class 2 receptors. 27599734 4 5 dep residues 703:710 arg1 KWRWRH 712:717 KWRWRH 712:717 KWRWRH 712:717 The characteristic structural features of IFNγR2 are concentrated in its N-terminal domain: an extensive π-cation motif of stacked residues KWRWRH, a NAG-W-NAG sandwich (where NAG stands for N-acetyl-D-glucosamine) and finally a helix formed by residues 78-85, which is unique among class 2 receptors. 27599734 5 6 theme glycosylation 950:962 arg1 importance 927:936 the importance 923:936 the importance of N-linked glycosylation to the stability of the protein 923:994 Mass spectrometry and mutational analyses showed the importance of N-linked glycosylation to the stability of the protein and confirmed the presence of two disulfide bonds. 27599734 1 7 theme adaptive 269:276 arg1 immunity 278:285 innate and adaptive immunity 258:285 innate and adaptive immunity against viral and also bacterial and protozoal infections 258:343 Interferon-γ receptor 2 is a cell-surface receptor that is required for interferon-γ signalling and therefore plays a critical immunoregulatory role in innate and adaptive immunity against viral and also bacterial and protozoal infections. 27599734 0 8 theme receptor 84:91 arg1 specificity 93:103 receptor specificity 84:103 receptor specificity 84:103 Crystal structure of human interferon-γ receptor 2 reveals the structural basis for receptor specificity. 27599734 3 9 theme fibronectin 542:552 arg1 domains 563:569 two fibronectin type III domains 538:569 two fibronectin type III domains 538:569 Similar to other class 2 receptors, IFNγR2 has two fibronectin type III domains. 27599734 4 10 theme structural 591:600 arg1 features 602:609 The characteristic structural features 572:609 The characteristic structural features of IFNγR2 572:619 The characteristic structural features of IFNγR2 are concentrated in its N-terminal domain: an extensive π-cation motif of stacked residues KWRWRH, a NAG-W-NAG sandwich (where NAG stands for N-acetyl-D-glucosamine) and finally a helix formed by residues 78-85, which is unique among class 2 receptors. 27599734 6 11 theme IFNγR2 1285:1290 arg1 interferon-γ 1241:1252 interferon-γ 1241:1252 interferon-γ 1241:1252 Structure-based bioinformatic analysis revealed independent evolutionary behaviour of both receptor domains and, together with multiple sequence alignment, identified putative binding sites for interferon-γ and receptor 1, the ligands of IFNγR2. 27599734 6 11 theme IFNγR2 1285:1290 arg1 ligands 1274:1280 the ligands 1270:1280 the ligands of IFNγR2 1270:1290 Structure-based bioinformatic analysis revealed independent evolutionary behaviour of both receptor domains and, together with multiple sequence alignment, identified putative binding sites for interferon-γ and receptor 1, the ligands of IFNγR2. 27599734 4 12 dep residues 817:824 arg1 78-85 826:830 78-85 826:830 78-85 826:830 The characteristic structural features of IFNγR2 are concentrated in its N-terminal domain: an extensive π-cation motif of stacked residues KWRWRH, a NAG-W-NAG sandwich (where NAG stands for N-acetyl-D-glucosamine) and finally a helix formed by residues 78-85, which is unique among class 2 receptors. 27599734 2 13 theme human 395:399 arg1 receptor 414:421 human interferon-γ receptor 2 395:423 human interferon-γ receptor 2 (IFNγR2) 395:432 A crystal structure of the extracellular part of human interferon-γ receptor 2 (IFNγR2) was solved by molecular replacement at 1.8 Å resolution. 27599734 2 13 theme human 395:399 arg1 IFNγR2 426:431 IFNγR2 426:431 IFNγR2 426:431 A crystal structure of the extracellular part of human interferon-γ receptor 2 (IFNγR2) was solved by molecular replacement at 1.8 Å resolution. 27599734 2 14 theme receptor 414:421 arg1 part 387:390 the extracellular part 369:390 the extracellular part of human interferon-γ receptor 2 (IFNγR2) 369:432 A crystal structure of the extracellular part of human interferon-γ receptor 2 (IFNγR2) was solved by molecular replacement at 1.8 Å resolution. 27599734 2 15 from resolution 479:488 arg1 replacement 458:468 molecular replacement 448:468 molecular replacement at 1.8 Å resolution 448:488 A crystal structure of the extracellular part of human interferon-γ receptor 2 (IFNγR2) was solved by molecular replacement at 1.8 Å resolution. 27599734 4 16 theme characteristic 576:589 arg1 features 602:609 The characteristic structural features 572:609 The characteristic structural features of IFNγR2 572:619 The characteristic structural features of IFNγR2 are concentrated in its N-terminal domain: an extensive π-cation motif of stacked residues KWRWRH, a NAG-W-NAG sandwich (where NAG stands for N-acetyl-D-glucosamine) and finally a helix formed by residues 78-85, which is unique among class 2 receptors. 27599734 4 17 theme residues 703:710 arg1 motif 686:690 an extensive π-cation motif 664:690 an extensive π-cation motif 664:690 The characteristic structural features of IFNγR2 are concentrated in its N-terminal domain: an extensive π-cation motif of stacked residues KWRWRH, a NAG-W-NAG sandwich (where NAG stands for N-acetyl-D-glucosamine) and finally a helix formed by residues 78-85, which is unique among class 2 receptors. 27599734 4 17 theme residues 703:710 arg1 unique 842:847 unique 842:847 unique 842:847 The characteristic structural features of IFNγR2 are concentrated in its N-terminal domain: an extensive π-cation motif of stacked residues KWRWRH, a NAG-W-NAG sandwich (where NAG stands for N-acetyl-D-glucosamine) and finally a helix formed by residues 78-85, which is unique among class 2 receptors. 27599734 6 18 theme evolutionary 1107:1118 arg1 behaviour 1120:1128 independent evolutionary behaviour 1095:1128 independent evolutionary behaviour of both receptor domains 1095:1153 Structure-based bioinformatic analysis revealed independent evolutionary behaviour of both receptor domains and, together with multiple sequence alignment, identified putative binding sites for interferon-γ and receptor 1, the ligands of IFNγR2. 27599734 2 19 theme interferon-γ 401:412 arg1 receptor 414:421 human interferon-γ receptor 2 395:423 human interferon-γ receptor 2 (IFNγR2) 395:432 A crystal structure of the extracellular part of human interferon-γ receptor 2 (IFNγR2) was solved by molecular replacement at 1.8 Å resolution. 27599734 2 19 theme interferon-γ 401:412 arg1 IFNγR2 426:431 IFNγR2 426:431 IFNγR2 426:431 A crystal structure of the extracellular part of human interferon-γ receptor 2 (IFNγR2) was solved by molecular replacement at 1.8 Å resolution. 27599734 2 20 theme molecular 448:456 arg1 replacement 458:468 molecular replacement 448:468 molecular replacement at 1.8 Å resolution 448:488 A crystal structure of the extracellular part of human interferon-γ receptor 2 (IFNγR2) was solved by molecular replacement at 1.8 Å resolution. 27599734 6 21 theme independent 1095:1105 arg1 behaviour 1120:1128 independent evolutionary behaviour 1095:1128 independent evolutionary behaviour of both receptor domains 1095:1153 Structure-based bioinformatic analysis revealed independent evolutionary behaviour of both receptor domains and, together with multiple sequence alignment, identified putative binding sites for interferon-γ and receptor 1, the ligands of IFNγR2. 27599734 5 22 link N-linked 941:948 arg1 glycosylation 950:962 N-linked glycosylation 941:962 N-linked glycosylation 941:962 Mass spectrometry and mutational analyses showed the importance of N-linked glycosylation to the stability of the protein and confirmed the presence of two disulfide bonds. 27599734 6 23 theme sequence 1183:1190 arg1 alignment 1192:1200 multiple sequence alignment 1174:1200 multiple sequence alignment 1174:1200 Structure-based bioinformatic analysis revealed independent evolutionary behaviour of both receptor domains and, together with multiple sequence alignment, identified putative binding sites for interferon-γ and receptor 1, the ligands of IFNγR2. 27599734 1 24 theme interferon-γ 178:189 arg1 signalling 191:200 interferon-γ signalling 178:200 interferon-γ signalling 178:200 Interferon-γ receptor 2 is a cell-surface receptor that is required for interferon-γ signalling and therefore plays a critical immunoregulatory role in innate and adaptive immunity against viral and also bacterial and protozoal infections. 27599734 0 25 theme Crystal 0:6 arg1 structure 8:16 Crystal structure 0:16 Crystal structure of human interferon-γ receptor 2 0:49 Crystal structure of human interferon-γ receptor 2 reveals the structural basis for receptor specificity. 27599734 6 26 theme multiple 1174:1181 arg1 alignment 1192:1200 multiple sequence alignment 1174:1200 multiple sequence alignment 1174:1200 Structure-based bioinformatic analysis revealed independent evolutionary behaviour of both receptor domains and, together with multiple sequence alignment, identified putative binding sites for interferon-γ and receptor 1, the ligands of IFNγR2. 27599734 4 27 theme extensive 667:675 arg1 motif 686:690 an extensive π-cation motif 664:690 an extensive π-cation motif 664:690 The characteristic structural features of IFNγR2 are concentrated in its N-terminal domain: an extensive π-cation motif of stacked residues KWRWRH, a NAG-W-NAG sandwich (where NAG stands for N-acetyl-D-glucosamine) and finally a helix formed by residues 78-85, which is unique among class 2 receptors. 27599734 4 27 theme extensive 667:675 arg1 unique 842:847 unique 842:847 unique 842:847 The characteristic structural features of IFNγR2 are concentrated in its N-terminal domain: an extensive π-cation motif of stacked residues KWRWRH, a NAG-W-NAG sandwich (where NAG stands for N-acetyl-D-glucosamine) and finally a helix formed by residues 78-85, which is unique among class 2 receptors. 27599734 0 28 theme human 21:25 arg1 receptor 40:47 human interferon-γ receptor 2 21:49 human interferon-γ receptor 2 21:49 Crystal structure of human interferon-γ receptor 2 reveals the structural basis for receptor specificity. 27599734 1 29 theme viral 295:299 arg1 infections 334:343 viral and also bacterial and protozoal infections 295:343 viral and also bacterial and protozoal infections 295:343 Interferon-γ receptor 2 is a cell-surface receptor that is required for interferon-γ signalling and therefore plays a critical immunoregulatory role in innate and adaptive immunity against viral and also bacterial and protozoal infections. 27599734 3 30 theme type 554:557 arg1 domains 563:569 two fibronectin type III domains 538:569 two fibronectin type III domains 538:569 Similar to other class 2 receptors, IFNγR2 has two fibronectin type III domains. 27599734 6 31 theme Structure-based 1047:1061 arg1 analysis 1077:1084 Structure-based bioinformatic analysis 1047:1084 Structure-based bioinformatic analysis 1047:1084 Structure-based bioinformatic analysis revealed independent evolutionary behaviour of both receptor domains and, together with multiple sequence alignment, identified putative binding sites for interferon-γ and receptor 1, the ligands of IFNγR2. 27599734 6 32 theme receptor 1138:1145 arg1 domains 1147:1153 both receptor domains 1133:1153 both receptor domains 1133:1153 Structure-based bioinformatic analysis revealed independent evolutionary behaviour of both receptor domains and, together with multiple sequence alignment, identified putative binding sites for interferon-γ and receptor 1, the ligands of IFNγR2. 27599734 4 33 theme IFNγR2 614:619 arg1 features 602:609 The characteristic structural features 572:609 The characteristic structural features of IFNγR2 572:619 The characteristic structural features of IFNγR2 are concentrated in its N-terminal domain: an extensive π-cation motif of stacked residues KWRWRH, a NAG-W-NAG sandwich (where NAG stands for N-acetyl-D-glucosamine) and finally a helix formed by residues 78-85, which is unique among class 2 receptors. 27599734 6 34 theme putative 1214:1221 arg1 sites 1231:1235 putative binding sites 1214:1235 putative binding sites for interferon-γ and receptor 1, the ligands of IFNγR2 1214:1290 Structure-based bioinformatic analysis revealed independent evolutionary behaviour of both receptor domains and, together with multiple sequence alignment, identified putative binding sites for interferon-γ and receptor 1, the ligands of IFNγR2. 27599734 1 35 theme Interferon-γ 106:117 arg1 receptor 148:155 a cell-surface receptor 133:155 a cell-surface receptor that is required for interferon-γ signalling and therefore plays a critical immunoregulatory role in innate and adaptive immunity against viral and also bacterial and protozoal infections 133:343 Interferon-γ receptor 2 is a cell-surface receptor that is required for interferon-γ signalling and therefore plays a critical immunoregulatory role in innate and adaptive immunity against viral and also bacterial and protozoal infections. 27599734 1 35 theme Interferon-γ 106:117 arg1 receptor 119:126 Interferon-γ receptor 2 106:128 Interferon-γ receptor 2 106:128 Interferon-γ receptor 2 is a cell-surface receptor that is required for interferon-γ signalling and therefore plays a critical immunoregulatory role in innate and adaptive immunity against viral and also bacterial and protozoal infections. 27599734 2 36 theme part 387:390 arg1 structure 356:364 A crystal structure 346:364 A crystal structure of the extracellular part of human interferon-γ receptor 2 (IFNγR2) 346:432 A crystal structure of the extracellular part of human interferon-γ receptor 2 (IFNγR2) was solved by molecular replacement at 1.8 Å resolution. 27599734 0 37 theme receptor 40:47 arg1 structure 8:16 Crystal structure 0:16 Crystal structure of human interferon-γ receptor 2 0:49 Crystal structure of human interferon-γ receptor 2 reveals the structural basis for receptor specificity. 27599734 3 38 theme other 502:506 arg1 receptors 516:524 other class 2 receptors 502:524 other class 2 receptors 502:524 Similar to other class 2 receptors, IFNγR2 has two fibronectin type III domains. 27599734 4 39 theme π-cation 677:684 arg1 motif 686:690 an extensive π-cation motif 664:690 an extensive π-cation motif 664:690 The characteristic structural features of IFNγR2 are concentrated in its N-terminal domain: an extensive π-cation motif of stacked residues KWRWRH, a NAG-W-NAG sandwich (where NAG stands for N-acetyl-D-glucosamine) and finally a helix formed by residues 78-85, which is unique among class 2 receptors. 27599734 4 39 theme π-cation 677:684 arg1 unique 842:847 unique 842:847 unique 842:847 The characteristic structural features of IFNγR2 are concentrated in its N-terminal domain: an extensive π-cation motif of stacked residues KWRWRH, a NAG-W-NAG sandwich (where NAG stands for N-acetyl-D-glucosamine) and finally a helix formed by residues 78-85, which is unique among class 2 receptors. 27599734 0 40 theme interferon-γ 27:38 arg1 receptor 40:47 human interferon-γ receptor 2 21:49 human interferon-γ receptor 2 21:49 Crystal structure of human interferon-γ receptor 2 reveals the structural basis for receptor specificity. 27599734 1 41 theme bacterial 310:318 arg1 infections 334:343 viral and also bacterial and protozoal infections 295:343 viral and also bacterial and protozoal infections 295:343 Interferon-γ receptor 2 is a cell-surface receptor that is required for interferon-γ signalling and therefore plays a critical immunoregulatory role in innate and adaptive immunity against viral and also bacterial and protozoal infections. 27599734 2 42 theme 1.8 Å 473:477 arg1 resolution 479:488 1.8 Å resolution 473:488 1.8 Å resolution 473:488 A crystal structure of the extracellular part of human interferon-γ receptor 2 (IFNγR2) was solved by molecular replacement at 1.8 Å resolution. 27599734 4 43 theme N-terminal 645:654 arg1 domain 656:661 its N-terminal domain 641:661 its N-terminal domain 641:661 The characteristic structural features of IFNγR2 are concentrated in its N-terminal domain: an extensive π-cation motif of stacked residues KWRWRH, a NAG-W-NAG sandwich (where NAG stands for N-acetyl-D-glucosamine) and finally a helix formed by residues 78-85, which is unique among class 2 receptors. 27599734 3 44 contain has 534:536 arg1 IFNγR2 527:532 IFNγR2 527:532 IFNγR2 527:532 Similar to other class 2 receptors, IFNγR2 has two fibronectin type III domains. 27599734 3 44 contain has 534:536 arg2 domains 563:569 two fibronectin type III domains 538:569 two fibronectin type III domains 538:569 Similar to other class 2 receptors, IFNγR2 has two fibronectin type III domains. 27599734 6 45 theme domains 1147:1153 arg1 behaviour 1120:1128 independent evolutionary behaviour 1095:1128 independent evolutionary behaviour of both receptor domains 1095:1153 Structure-based bioinformatic analysis revealed independent evolutionary behaviour of both receptor domains and, together with multiple sequence alignment, identified putative binding sites for interferon-γ and receptor 1, the ligands of IFNγR2. 27599734 5 46 theme mutational 896:905 arg1 analyses 907:914 mutational analyses 896:914 mutational analyses 896:914 Mass spectrometry and mutational analyses showed the importance of N-linked glycosylation to the stability of the protein and confirmed the presence of two disulfide bonds. 27599734 1 47 theme protozoal 324:332 arg1 infections 334:343 viral and also bacterial and protozoal infections 295:343 viral and also bacterial and protozoal infections 295:343 Interferon-γ receptor 2 is a cell-surface receptor that is required for interferon-γ signalling and therefore plays a critical immunoregulatory role in innate and adaptive immunity against viral and also bacterial and protozoal infections. 27599734 6 48 theme bioinformatic 1063:1075 arg1 analysis 1077:1084 Structure-based bioinformatic analysis 1047:1084 Structure-based bioinformatic analysis 1047:1084 Structure-based bioinformatic analysis revealed independent evolutionary behaviour of both receptor domains and, together with multiple sequence alignment, identified putative binding sites for interferon-γ and receptor 1, the ligands of IFNγR2. 27599734 5 49 theme disulfide 1030:1038 arg1 bonds 1040:1044 two disulfide bonds 1026:1044 two disulfide bonds 1026:1044 Mass spectrometry and mutational analyses showed the importance of N-linked glycosylation to the stability of the protein and confirmed the presence of two disulfide bonds. 27599734 2 50 theme crystal 348:354 arg1 structure 356:364 A crystal structure 346:364 A crystal structure of the extracellular part of human interferon-γ receptor 2 (IFNγR2) 346:432 A crystal structure of the extracellular part of human interferon-γ receptor 2 (IFNγR2) was solved by molecular replacement at 1.8 Å resolution. 27599734 5 51 theme bonds 1040:1044 arg1 presence 1014:1021 the presence 1010:1021 the presence of two disulfide bonds 1010:1044 Mass spectrometry and mutational analyses showed the importance of N-linked glycosylation to the stability of the protein and confirmed the presence of two disulfide bonds. 27599734 4 52 theme NAG-W-NAG 722:730 arg1 sandwich 732:739 a NAG-W-NAG sandwich 720:739 a NAG-W-NAG sandwich (where NAG stands for N-acetyl-D-glucosamine) 720:785 The characteristic structural features of IFNγR2 are concentrated in its N-terminal domain: an extensive π-cation motif of stacked residues KWRWRH, a NAG-W-NAG sandwich (where NAG stands for N-acetyl-D-glucosamine) and finally a helix formed by residues 78-85, which is unique among class 2 receptors. 27599734 4 52 theme NAG-W-NAG 722:730 arg1 residues 703:710 stacked residues 695:710 stacked residues KWRWRH, a NAG-W-NAG sandwich (where NAG stands for N-acetyl-D-glucosamine) and finally a helix formed by residues 78-85 695:830 The characteristic structural features of IFNγR2 are concentrated in its N-terminal domain: an extensive π-cation motif of stacked residues KWRWRH, a NAG-W-NAG sandwich (where NAG stands for N-acetyl-D-glucosamine) and finally a helix formed by residues 78-85, which is unique among class 2 receptors. 27599734 5 53 theme N-linked 941:948 arg1 glycosylation 950:962 N-linked glycosylation 941:962 N-linked glycosylation 941:962 Mass spectrometry and mutational analyses showed the importance of N-linked glycosylation to the stability of the protein and confirmed the presence of two disulfide bonds. 27599734 1 54 theme critical 224:231 arg1 role 250:253 a critical immunoregulatory role 222:253 a critical immunoregulatory role 222:253 Interferon-γ receptor 2 is a cell-surface receptor that is required for interferon-γ signalling and therefore plays a critical immunoregulatory role in innate and adaptive immunity against viral and also bacterial and protozoal infections. 27599734 5 55 theme protein 988:994 arg1 stability 971:979 the stability 967:979 the stability of the protein 967:994 Mass spectrometry and mutational analyses showed the importance of N-linked glycosylation to the stability of the protein and confirmed the presence of two disulfide bonds. 27599734 5 56 theme Mass 874:877 arg1 spectrometry 879:890 Mass spectrometry 874:890 Mass spectrometry 874:890 Mass spectrometry and mutational analyses showed the importance of N-linked glycosylation to the stability of the protein and confirmed the presence of two disulfide bonds. 27599734 1 57 theme immunoregulatory 233:248 arg1 role 250:253 a critical immunoregulatory role 222:253 a critical immunoregulatory role 222:253 Interferon-γ receptor 2 is a cell-surface receptor that is required for interferon-γ signalling and therefore plays a critical immunoregulatory role in innate and adaptive immunity against viral and also bacterial and protozoal infections. 27599734 0 58 theme structural 63:72 arg1 basis 74:78 the structural basis 59:78 the structural basis for receptor specificity 59:103 Crystal structure of human interferon-γ receptor 2 reveals the structural basis for receptor specificity. 27599734 1 59 theme cell-surface 135:146 arg1 receptor 148:155 a cell-surface receptor 133:155 a cell-surface receptor that is required for interferon-γ signalling and therefore plays a critical immunoregulatory role in innate and adaptive immunity against viral and also bacterial and protozoal infections 133:343 Interferon-γ receptor 2 is a cell-surface receptor that is required for interferon-γ signalling and therefore plays a critical immunoregulatory role in innate and adaptive immunity against viral and also bacterial and protozoal infections. 27599734 1 59 theme cell-surface 135:146 arg1 receptor 119:126 Interferon-γ receptor 2 106:128 Interferon-γ receptor 2 106:128 Interferon-γ receptor 2 is a cell-surface receptor that is required for interferon-γ signalling and therefore plays a critical immunoregulatory role in innate and adaptive immunity against viral and also bacterial and protozoal infections. 27599734 6 60 theme binding 1223:1229 arg1 sites 1231:1235 putative binding sites 1214:1235 putative binding sites for interferon-γ and receptor 1, the ligands of IFNγR2 1214:1290 Structure-based bioinformatic analysis revealed independent evolutionary behaviour of both receptor domains and, together with multiple sequence alignment, identified putative binding sites for interferon-γ and receptor 1, the ligands of IFNγR2. 27599734 2 61 theme extracellular 373:385 arg1 part 387:390 the extracellular part 369:390 the extracellular part of human interferon-γ receptor 2 (IFNγR2) 369:432 A crystal structure of the extracellular part of human interferon-γ receptor 2 (IFNγR2) was solved by molecular replacement at 1.8 Å resolution. 24155380 0 0 theme stalk 87:91 arg1 domain 93:98 the conserved stalk domain 73:98 the conserved stalk domain 73:98 Guiding the immune response against influenza virus hemagglutinin toward the conserved stalk domain by hyperglycosylation of the globular head domain. 24155380 4 1 theme influenza 560:568 arg1 challenge 576:584 influenza virus challenge 560:584 influenza virus challenge 560:584 Upon influenza virus challenge, mice vaccinated with the hyperglycosylated hemagglutinin were better protected against morbidity and mortality than mice receiving the wild-type hemagglutinin. 24155380 1 2 theme virus 161:165 arg1 hemagglutinin 167:179 Influenza virus hemagglutinin 151:179 Influenza virus hemagglutinin 151:179 Influenza virus hemagglutinin consists of a highly variable and immunodominant head domain and a more conserved but immunosubdominant stalk domain. 24155380 1 3 theme conserved 253:261 arg1 domain 291:296 a more conserved but immunosubdominant stalk domain 246:296 a more conserved but immunosubdominant stalk domain 246:296 Influenza virus hemagglutinin consists of a highly variable and immunodominant head domain and a more conserved but immunosubdominant stalk domain. 24155380 0 4 theme conserved 77:85 arg1 domain 93:98 the conserved stalk domain 73:98 the conserved stalk domain 73:98 Guiding the immune response against influenza virus hemagglutinin toward the conserved stalk domain by hyperglycosylation of the globular head domain. 24155380 3 5 gly hyperglycosylated 431:447 arg1 hemagglutinin 449:461 The hyperglycosylated hemagglutinin 427:461 The hyperglycosylated hemagglutinin 427:461 The hyperglycosylated hemagglutinin enhanced stalk-directed seroreactivity while dampening the head response in immunized mice. 24155380 1 6 theme immunosubdominant 267:283 arg1 domain 291:296 a more conserved but immunosubdominant stalk domain 246:296 a more conserved but immunosubdominant stalk domain 246:296 Influenza virus hemagglutinin consists of a highly variable and immunodominant head domain and a more conserved but immunosubdominant stalk domain. 24155380 1 7 theme stalk 285:289 arg1 domain 291:296 a more conserved but immunosubdominant stalk domain 246:296 a more conserved but immunosubdominant stalk domain 246:296 Influenza virus hemagglutinin consists of a highly variable and immunodominant head domain and a more conserved but immunosubdominant stalk domain. 24155380 3 8 theme stalk-directed 472:485 arg1 seroreactivity 487:500 stalk-directed seroreactivity 472:500 stalk-directed seroreactivity 472:500 The hyperglycosylated hemagglutinin enhanced stalk-directed seroreactivity while dampening the head response in immunized mice. 24155380 3 9 theme hyperglycosylated 431:447 arg1 hemagglutinin 449:461 The hyperglycosylated hemagglutinin 427:461 The hyperglycosylated hemagglutinin 427:461 The hyperglycosylated hemagglutinin enhanced stalk-directed seroreactivity while dampening the head response in immunized mice. 24155380 2 10 theme antigenic 410:418 arg1 sites 420:424 the immunodominant antigenic sites 391:424 the immunodominant antigenic sites 391:424 We introduced seven N-linked glycosylation sites in the hemagglutinin head domain to shield the immunodominant antigenic sites. 24155380 2 11 theme glycosylation 328:340 arg1 sites 342:346 seven N-linked glycosylation sites 313:346 seven N-linked glycosylation sites 313:346 We introduced seven N-linked glycosylation sites in the hemagglutinin head domain to shield the immunodominant antigenic sites. 24155380 2 12 theme immunodominant 395:408 arg1 sites 420:424 the immunodominant antigenic sites 391:424 the immunodominant antigenic sites 391:424 We introduced seven N-linked glycosylation sites in the hemagglutinin head domain to shield the immunodominant antigenic sites. 24155380 4 13 theme hyperglycosylated 612:628 arg1 hemagglutinin 630:642 the hyperglycosylated hemagglutinin 608:642 the hyperglycosylated hemagglutinin 608:642 Upon influenza virus challenge, mice vaccinated with the hyperglycosylated hemagglutinin were better protected against morbidity and mortality than mice receiving the wild-type hemagglutinin. 24155380 0 14 theme globular 129:136 arg1 domain 143:148 the globular head domain 125:148 the globular head domain 125:148 Guiding the immune response against influenza virus hemagglutinin toward the conserved stalk domain by hyperglycosylation of the globular head domain. 24155380 0 15 gly hyperglycosylation 103:120 arg1 domain 143:148 the globular head domain 125:148 the globular head domain 125:148 Guiding the immune response against influenza virus hemagglutinin toward the conserved stalk domain by hyperglycosylation of the globular head domain. 24155380 1 16 theme variable 202:209 arg1 domain 235:240 a highly variable and immunodominant head domain 193:240 a highly variable and immunodominant head domain 193:240 Influenza virus hemagglutinin consists of a highly variable and immunodominant head domain and a more conserved but immunosubdominant stalk domain. 24155380 0 17 theme immune 12:17 arg1 response 19:26 the immune response 8:26 the immune response against influenza virus hemagglutinin toward the conserved stalk domain 8:98 Guiding the immune response against influenza virus hemagglutinin toward the conserved stalk domain by hyperglycosylation of the globular head domain. 24155380 0 18 theme influenza 36:44 arg1 hemagglutinin 52:64 influenza virus hemagglutinin 36:64 influenza virus hemagglutinin 36:64 Guiding the immune response against influenza virus hemagglutinin toward the conserved stalk domain by hyperglycosylation of the globular head domain. 24155380 0 19 theme domain 143:148 arg1 hyperglycosylation 103:120 hyperglycosylation 103:120 hyperglycosylation of the globular head domain 103:148 Guiding the immune response against influenza virus hemagglutinin toward the conserved stalk domain by hyperglycosylation of the globular head domain. 24155380 1 20 theme immunodominant 215:228 arg1 domain 235:240 a highly variable and immunodominant head domain 193:240 a highly variable and immunodominant head domain 193:240 Influenza virus hemagglutinin consists of a highly variable and immunodominant head domain and a more conserved but immunosubdominant stalk domain. 24155380 2 21 link N-linked 319:326 arg1 sites 342:346 seven N-linked glycosylation sites 313:346 seven N-linked glycosylation sites 313:346 We introduced seven N-linked glycosylation sites in the hemagglutinin head domain to shield the immunodominant antigenic sites. 24155380 0 22 theme head 138:141 arg1 domain 143:148 the globular head domain 125:148 the globular head domain 125:148 Guiding the immune response against influenza virus hemagglutinin toward the conserved stalk domain by hyperglycosylation of the globular head domain. 24155380 4 23 gly hyperglycosylated 612:628 arg1 hemagglutinin 630:642 the hyperglycosylated hemagglutinin 608:642 the hyperglycosylated hemagglutinin 608:642 Upon influenza virus challenge, mice vaccinated with the hyperglycosylated hemagglutinin were better protected against morbidity and mortality than mice receiving the wild-type hemagglutinin. 24155380 1 24 theme head 230:233 arg1 domain 235:240 a highly variable and immunodominant head domain 193:240 a highly variable and immunodominant head domain 193:240 Influenza virus hemagglutinin consists of a highly variable and immunodominant head domain and a more conserved but immunosubdominant stalk domain. 24155380 2 25 theme head 369:372 arg1 domain 374:379 the hemagglutinin head domain 351:379 the hemagglutinin head domain 351:379 We introduced seven N-linked glycosylation sites in the hemagglutinin head domain to shield the immunodominant antigenic sites. 24155380 0 26 theme virus 46:50 arg1 hemagglutinin 52:64 influenza virus hemagglutinin 36:64 influenza virus hemagglutinin 36:64 Guiding the immune response against influenza virus hemagglutinin toward the conserved stalk domain by hyperglycosylation of the globular head domain. 24155380 3 27 from response 527:534 arg1 mice 549:552 immunized mice 539:552 immunized mice 539:552 The hyperglycosylated hemagglutinin enhanced stalk-directed seroreactivity while dampening the head response in immunized mice. 24155380 2 28 theme hemagglutinin 355:367 arg1 domain 374:379 the hemagglutinin head domain 351:379 the hemagglutinin head domain 351:379 We introduced seven N-linked glycosylation sites in the hemagglutinin head domain to shield the immunodominant antigenic sites. 24155380 3 29 theme immunized 539:547 arg1 mice 549:552 immunized mice 539:552 immunized mice 539:552 The hyperglycosylated hemagglutinin enhanced stalk-directed seroreactivity while dampening the head response in immunized mice. 24155380 2 30 theme N-linked 319:326 arg1 sites 342:346 seven N-linked glycosylation sites 313:346 seven N-linked glycosylation sites 313:346 We introduced seven N-linked glycosylation sites in the hemagglutinin head domain to shield the immunodominant antigenic sites. 24155380 2 31 gly glycosylation 328:340 arg2 sites 342:346 seven N-linked glycosylation sites 313:346 seven N-linked glycosylation sites 313:346 We introduced seven N-linked glycosylation sites in the hemagglutinin head domain to shield the immunodominant antigenic sites. 24155380 2 31 gly glycosylation 328:340 arg2 seven 313:317 seven 313:317 seven 313:317 We introduced seven N-linked glycosylation sites in the hemagglutinin head domain to shield the immunodominant antigenic sites. 24155380 3 32 theme head 522:525 arg1 response 527:534 the head response 518:534 the head response in immunized mice 518:552 The hyperglycosylated hemagglutinin enhanced stalk-directed seroreactivity while dampening the head response in immunized mice. 24155380 4 33 theme wild-type 722:730 arg1 hemagglutinin 732:744 the wild-type hemagglutinin 718:744 the wild-type hemagglutinin 718:744 Upon influenza virus challenge, mice vaccinated with the hyperglycosylated hemagglutinin were better protected against morbidity and mortality than mice receiving the wild-type hemagglutinin. 24155380 4 34 theme virus 570:574 arg1 challenge 576:584 influenza virus challenge 560:584 influenza virus challenge 560:584 Upon influenza virus challenge, mice vaccinated with the hyperglycosylated hemagglutinin were better protected against morbidity and mortality than mice receiving the wild-type hemagglutinin. 24155380 1 35 theme Influenza 151:159 arg1 hemagglutinin 167:179 Influenza virus hemagglutinin 151:179 Influenza virus hemagglutinin 151:179 Influenza virus hemagglutinin consists of a highly variable and immunodominant head domain and a more conserved but immunosubdominant stalk domain. 27707925 7 0 gly glycoproteins 1358:1370 arg1 glycoproteins 1358:1370 recombinant gp120 glycoproteins 1340:1370 recombinant gp120 glycoproteins 1340:1370 This effect of the glycan density on the processing state was also supported by the analysis of a cross-clade panel of recombinant gp120 glycoproteins. 27707925 4 1 theme HIV 563:565 arg1 glycan 567:572 the HIV glycan shield 559:579 the HIV glycan shield 559:579 In response to the host immune system, the HIV glycan shield is constantly evolving through mutations affecting both the positions and numbers of potential N-linked glycosylation sites (PNGSs). 27707925 6 2 from changes 1051:1057 arg1 positioning 1078:1088 positioning 1078:1088 positioning 1078:1088 By analyzing the intrinsic mannose patch from a panel of recombinant CAP256 gp120s displaying high protein sequence variability and changes in PNGS number and positioning, we show that the intrinsic mannose patch persists throughout the course of HIV infection and correlates with the number of PNGSs. 27707925 6 2 from changes 1051:1057 arg1 number 1067:1072 number 1067:1072 number 1067:1072 By analyzing the intrinsic mannose patch from a panel of recombinant CAP256 gp120s displaying high protein sequence variability and changes in PNGS number and positioning, we show that the intrinsic mannose patch persists throughout the course of HIV infection and correlates with the number of PNGSs. 27707925 6 2 from changes 1051:1057 arg1 PNGS 1062:1065 PNGS number and positioning 1062:1088 PNGS number and positioning 1062:1088 By analyzing the intrinsic mannose patch from a panel of recombinant CAP256 gp120s displaying high protein sequence variability and changes in PNGS number and positioning, we show that the intrinsic mannose patch persists throughout the course of HIV infection and correlates with the number of PNGSs. 27707925 9 3 theme important 1631:1639 arg1 target 1641:1646 an important target 1628:1646 an important target for HIV vaccine strategies 1628:1673 The persistence of the intrinsic mannose patch over the course of HIV infection further highlights this epitope as an important target for HIV vaccine strategies. 27707925 9 3 theme important 1631:1639 arg1 epitope 1617:1623 this epitope 1612:1623 this epitope 1612:1623 The persistence of the intrinsic mannose patch over the course of HIV infection further highlights this epitope as an important target for HIV vaccine strategies. 27707925 9 4 theme mannose 1546:1552 arg1 patch 1554:1558 the intrinsic mannose patch 1532:1558 the intrinsic mannose patch 1532:1558 The persistence of the intrinsic mannose patch over the course of HIV infection further highlights this epitope as an important target for HIV vaccine strategies. 27707925 12 5 from system 2162:2167 arg1 pressure 2132:2139 constant pressure 2123:2139 constant pressure from the host immune system 2123:2167 This glycan shield is a target for many of the recently isolated anti-HIV bnAbs and is therefore under constant pressure from the host immune system, leading to changes in both glycan site frequency and location. 27707925 12 5 from system 2162:2167 arg1 glycan 2025:2030 This glycan shield 2020:2037 This glycan shield 2020:2037 This glycan shield is a target for many of the recently isolated anti-HIV bnAbs and is therefore under constant pressure from the host immune system, leading to changes in both glycan site frequency and location. 27707925 12 5 from system 2162:2167 arg1 target 2044:2049 a target 2042:2049 a target for many of the recently isolated anti-HIV bnAbs 2042:2098 This glycan shield is a target for many of the recently isolated anti-HIV bnAbs and is therefore under constant pressure from the host immune system, leading to changes in both glycan site frequency and location. 27707925 6 6 theme recombinant 976:986 arg1 gp120s 995:1000 recombinant CAP256 gp120s 976:1000 recombinant CAP256 gp120s displaying high protein sequence variability 976:1045 By analyzing the intrinsic mannose patch from a panel of recombinant CAP256 gp120s displaying high protein sequence variability and changes in PNGS number and positioning, we show that the intrinsic mannose patch persists throughout the course of HIV infection and correlates with the number of PNGSs. 27707925 7 7 from effect 1226:1231 arg1 state 1273:1277 the processing state 1258:1277 the processing state 1258:1277 This effect of the glycan density on the processing state was also supported by the analysis of a cross-clade panel of recombinant gp120 glycoproteins. 27707925 10 8 theme response 1878:1885 arg1 elicitation 1767:1777 elicitation 1767:1777 elicitation of broadly neutralizing antibodies (bnAbs) 1767:1820 IMPORTANCE: Development of an HIV vaccine is critical for control of the HIV pandemic, and elicitation of broadly neutralizing antibodies (bnAbs) is likely to be a key component of a successful vaccine response. 27707925 10 8 theme response 1878:1885 arg1 component 1844:1852 a key component 1838:1852 a key component of a successful vaccine response 1838:1885 IMPORTANCE: Development of an HIV vaccine is critical for control of the HIV pandemic, and elicitation of broadly neutralizing antibodies (bnAbs) is likely to be a key component of a successful vaccine response. 27707925 2 9 theme enzymatic 252:260 arg1 processing 262:271 enzymatic processing 252:271 enzymatic processing 252:271 The high density of glycosylation on the viral spike limits enzymatic processing, resulting in numerous underprocessed oligomannose-type glycans. 27707925 5 10 theme shifting 828:835 arg1 glycan 837:842 the shifting glycan 824:842 the shifting glycan shield during HIV infection 824:870 Here, using longitudinal Env sequences from a clade C-infected individual (CAP256), we measured the impact of the shifting glycan shield during HIV infection on the abundance of oligomannose-type glycans. 27707925 9 11 theme vaccine 1656:1662 arg1 strategies 1664:1673 HIV vaccine strategies 1652:1673 HIV vaccine strategies 1652:1673 The persistence of the intrinsic mannose patch over the course of HIV infection further highlights this epitope as an important target for HIV vaccine strategies. 27707925 6 12 theme PNGSs 1214:1218 arg1 number 1204:1209 the number 1200:1209 the number of PNGSs 1200:1218 By analyzing the intrinsic mannose patch from a panel of recombinant CAP256 gp120s displaying high protein sequence variability and changes in PNGS number and positioning, we show that the intrinsic mannose patch persists throughout the course of HIV infection and correlates with the number of PNGSs. 27707925 2 13 theme underprocessed 296:309 arg1 glycans 329:335 numerous underprocessed oligomannose-type glycans 287:335 numerous underprocessed oligomannose-type glycans 287:335 The high density of glycosylation on the viral spike limits enzymatic processing, resulting in numerous underprocessed oligomannose-type glycans. 27707925 1 14 theme N-linked 174:181 arg1 glycans 183:189 host-derived N-linked glycans 161:189 host-derived N-linked glycans 161:189 The HIV envelope glycoprotein (Env) is extensively modified with host-derived N-linked glycans. 27707925 6 15 theme mannose 946:952 arg1 patch 954:958 the intrinsic mannose patch 932:958 the intrinsic mannose patch 932:958 By analyzing the intrinsic mannose patch from a panel of recombinant CAP256 gp120s displaying high protein sequence variability and changes in PNGS number and positioning, we show that the intrinsic mannose patch persists throughout the course of HIV infection and correlates with the number of PNGSs. 27707925 7 16 theme gp120 1352:1356 arg1 glycoproteins 1358:1370 recombinant gp120 glycoproteins 1340:1370 recombinant gp120 glycoproteins 1340:1370 This effect of the glycan density on the processing state was also supported by the analysis of a cross-clade panel of recombinant gp120 glycoproteins. 27707925 11 17 theme N-linked 1963:1970 arg1 glycans 1972:1978 host-derived N-linked glycans 1950:1978 host-derived N-linked glycans often referred to as the glycan shield 1950:2017 The HIV envelope glycoprotein (Env) is covered in an array of host-derived N-linked glycans often referred to as the glycan shield. 27707925 14 18 theme mannose 2522:2528 arg1 patch 2530:2534 the mannose patch 2518:2534 the mannose patch 2518:2534 We show that despite this variation in glycan site positioning and frequency over the course of HIV infection, the mannose patch is a conserved feature throughout, making it a stable target for HIV vaccine design. 27707925 14 18 theme mannose 2522:2528 arg1 feature 2551:2557 a conserved feature 2539:2557 a conserved feature throughout 2539:2568 We show that despite this variation in glycan site positioning and frequency over the course of HIV infection, the mannose patch is a conserved feature throughout, making it a stable target for HIV vaccine design. 27707925 1 19 gly glycoprotein 113:124 arg1 glycoprotein 113:124 The HIV envelope glycoprotein 96:124 The HIV envelope glycoprotein (Env) 96:130 The HIV envelope glycoprotein (Env) is extensively modified with host-derived N-linked glycans. 27707925 1 19 gly glycoprotein 113:124 arg1 Env 127:129 Env 127:129 Env 127:129 The HIV envelope glycoprotein (Env) is extensively modified with host-derived N-linked glycans. 27707925 2 20 theme glycosylation 212:224 arg1 density 201:207 The high density 192:207 The high density of glycosylation on the viral spike 192:243 The high density of glycosylation on the viral spike limits enzymatic processing, resulting in numerous underprocessed oligomannose-type glycans. 27707925 5 21 from impact 814:819 arg1 abundance 879:887 the abundance 875:887 the abundance of oligomannose-type glycans 875:916 Here, using longitudinal Env sequences from a clade C-infected individual (CAP256), we measured the impact of the shifting glycan shield during HIV infection on the abundance of oligomannose-type glycans. 27707925 7 22 theme cross-clade 1319:1329 arg1 panel 1331:1335 a cross-clade panel 1317:1335 a cross-clade panel of recombinant gp120 glycoproteins 1317:1370 This effect of the glycan density on the processing state was also supported by the analysis of a cross-clade panel of recombinant gp120 glycoproteins. 27707925 11 23 theme envelope 1896:1903 arg1 glycoprotein 1905:1916 The HIV envelope glycoprotein 1888:1916 The HIV envelope glycoprotein (Env) 1888:1922 The HIV envelope glycoprotein (Env) is covered in an array of host-derived N-linked glycans often referred to as the glycan shield. 27707925 11 23 theme envelope 1896:1903 arg1 Env 1919:1921 Env 1919:1921 Env 1919:1921 The HIV envelope glycoprotein (Env) is covered in an array of host-derived N-linked glycans often referred to as the glycan shield. 27707925 1 24 theme envelope 104:111 arg1 glycoprotein 113:124 The HIV envelope glycoprotein 96:124 The HIV envelope glycoprotein (Env) 96:130 The HIV envelope glycoprotein (Env) is extensively modified with host-derived N-linked glycans. 27707925 1 24 theme envelope 104:111 arg1 Env 127:129 Env 127:129 Env 127:129 The HIV envelope glycoprotein (Env) is extensively modified with host-derived N-linked glycans. 27707925 14 25 theme HIV 2503:2505 arg1 infection 2507:2515 HIV infection 2503:2515 HIV infection 2503:2515 We show that despite this variation in glycan site positioning and frequency over the course of HIV infection, the mannose patch is a conserved feature throughout, making it a stable target for HIV vaccine design. 27707925 8 26 theme clustering 1438:1447 arg1 importance 1417:1426 the importance 1413:1426 the importance of glycan clustering for the generation of carbohydrate epitopes for anti-HIV bnAbs 1413:1510 Together, these observations underscore the importance of glycan clustering for the generation of carbohydrate epitopes for anti-HIV bnAbs. 27707925 10 27 theme antibodies 1803:1812 arg1 elicitation 1767:1777 elicitation 1767:1777 elicitation of broadly neutralizing antibodies (bnAbs) 1767:1820 IMPORTANCE: Development of an HIV vaccine is critical for control of the HIV pandemic, and elicitation of broadly neutralizing antibodies (bnAbs) is likely to be a key component of a successful vaccine response. 27707925 10 27 theme antibodies 1803:1812 arg1 component 1844:1852 a key component 1838:1852 a key component of a successful vaccine response 1838:1885 IMPORTANCE: Development of an HIV vaccine is critical for control of the HIV pandemic, and elicitation of broadly neutralizing antibodies (bnAbs) is likely to be a key component of a successful vaccine response. 27707925 5 28 theme oligomannose-type 892:908 arg1 glycans 910:916 oligomannose-type glycans 892:916 oligomannose-type glycans 892:916 Here, using longitudinal Env sequences from a clade C-infected individual (CAP256), we measured the impact of the shifting glycan shield during HIV infection on the abundance of oligomannose-type glycans. 27707925 6 29 theme gp120s 995:1000 arg1 panel 967:971 a panel 965:971 a panel of recombinant CAP256 gp120s displaying high protein sequence variability 965:1045 By analyzing the intrinsic mannose patch from a panel of recombinant CAP256 gp120s displaying high protein sequence variability and changes in PNGS number and positioning, we show that the intrinsic mannose patch persists throughout the course of HIV infection and correlates with the number of PNGSs. 27707925 6 29 theme gp120s 995:1000 arg1 changes 1051:1057 changes 1051:1057 changes in PNGS number and positioning 1051:1088 By analyzing the intrinsic mannose patch from a panel of recombinant CAP256 gp120s displaying high protein sequence variability and changes in PNGS number and positioning, we show that the intrinsic mannose patch persists throughout the course of HIV infection and correlates with the number of PNGSs. 27707925 11 30 link host-derived 1950:1961 arg1 glycans 1972:1978 host-derived N-linked glycans 1950:1978 host-derived N-linked glycans often referred to as the glycan shield 1950:2017 The HIV envelope glycoprotein (Env) is covered in an array of host-derived N-linked glycans often referred to as the glycan shield. 27707925 6 31 theme infection 1170:1178 arg1 course 1156:1161 the course 1152:1161 the course of HIV infection 1152:1178 By analyzing the intrinsic mannose patch from a panel of recombinant CAP256 gp120s displaying high protein sequence variability and changes in PNGS number and positioning, we show that the intrinsic mannose patch persists throughout the course of HIV infection and correlates with the number of PNGSs. 27707925 14 32 theme vaccine 2605:2611 arg1 design 2613:2618 HIV vaccine design 2601:2618 HIV vaccine design 2601:2618 We show that despite this variation in glycan site positioning and frequency over the course of HIV infection, the mannose patch is a conserved feature throughout, making it a stable target for HIV vaccine design. 27707925 4 33 theme N-linked 676:683 arg1 PNGSs 706:710 PNGSs 706:710 PNGSs 706:710 In response to the host immune system, the HIV glycan shield is constantly evolving through mutations affecting both the positions and numbers of potential N-linked glycosylation sites (PNGSs). 27707925 4 33 theme N-linked 676:683 arg1 sites 699:703 potential N-linked glycosylation sites 666:703 potential N-linked glycosylation sites (PNGSs) 666:711 In response to the host immune system, the HIV glycan shield is constantly evolving through mutations affecting both the positions and numbers of potential N-linked glycosylation sites (PNGSs). 27707925 0 34 theme Mannose 51:57 arg1 Patch 59:63 the Mannose Patch 47:63 the Mannose Patch 47:63 HIV-1 Glycan Density Drives the Persistence of the Mannose Patch within an Infected Individual. 27707925 5 35 from individual 777:786 arg1 sequences 743:751 longitudinal Env sequences 726:751 longitudinal Env sequences from a clade C-infected individual (CAP256) 726:795 Here, using longitudinal Env sequences from a clade C-infected individual (CAP256), we measured the impact of the shifting glycan shield during HIV infection on the abundance of oligomannose-type glycans. 27707925 5 36 theme HIV 858:860 arg1 infection 862:870 HIV infection 858:870 HIV infection 858:870 Here, using longitudinal Env sequences from a clade C-infected individual (CAP256), we measured the impact of the shifting glycan shield during HIV infection on the abundance of oligomannose-type glycans. 27707925 4 37 link N-linked 676:683 arg1 PNGSs 706:710 PNGSs 706:710 PNGSs 706:710 In response to the host immune system, the HIV glycan shield is constantly evolving through mutations affecting both the positions and numbers of potential N-linked glycosylation sites (PNGSs). 27707925 4 37 link N-linked 676:683 arg1 sites 699:703 potential N-linked glycosylation sites 666:703 potential N-linked glycosylation sites (PNGSs) 666:711 In response to the host immune system, the HIV glycan shield is constantly evolving through mutations affecting both the positions and numbers of potential N-linked glycosylation sites (PNGSs). 27707925 11 38 theme glycans 1972:1978 arg1 array 1941:1945 an array 1938:1945 an array of host-derived N-linked glycans often referred to as the glycan shield 1938:2017 The HIV envelope glycoprotein (Env) is covered in an array of host-derived N-linked glycans often referred to as the glycan shield. 27707925 4 39 theme sites 699:703 arg1 numbers 655:661 numbers 655:661 numbers 655:661 In response to the host immune system, the HIV glycan shield is constantly evolving through mutations affecting both the positions and numbers of potential N-linked glycosylation sites (PNGSs). 27707925 4 39 theme sites 699:703 arg1 positions 641:649 positions 641:649 positions 641:649 In response to the host immune system, the HIV glycan shield is constantly evolving through mutations affecting both the positions and numbers of potential N-linked glycosylation sites (PNGSs). 27707925 8 40 theme epitopes 1484:1491 arg1 generation 1457:1466 the generation 1453:1466 the generation of carbohydrate epitopes for anti-HIV bnAbs 1453:1510 Together, these observations underscore the importance of glycan clustering for the generation of carbohydrate epitopes for anti-HIV bnAbs. 27707925 12 41 theme host 2150:2153 arg1 system 2162:2167 the host immune system 2146:2167 the host immune system 2146:2167 This glycan shield is a target for many of the recently isolated anti-HIV bnAbs and is therefore under constant pressure from the host immune system, leading to changes in both glycan site frequency and location. 27707925 0 42 theme Infected 75:82 arg1 Individual 84:93 an Infected Individual 72:93 an Infected Individual 72:93 HIV-1 Glycan Density Drives the Persistence of the Mannose Patch within an Infected Individual. 27707925 13 43 theme HIV 2344:2346 arg1 Env 2348:2350 the HIV Env 2340:2350 the HIV Env 2340:2350 This study aimed to determine whether these genetic changes impacted the eventual processing of glycans on the HIV Env and the susceptibility of the virus to neutralization. 27707925 14 44 theme site 2453:2456 arg1 positioning 2458:2468 glycan site positioning 2446:2468 glycan site positioning 2446:2468 We show that despite this variation in glycan site positioning and frequency over the course of HIV infection, the mannose patch is a conserved feature throughout, making it a stable target for HIV vaccine design. 27707925 8 45 theme anti-HIV 1497:1504 arg1 bnAbs 1506:1510 anti-HIV bnAbs 1497:1510 anti-HIV bnAbs 1497:1510 Together, these observations underscore the importance of glycan clustering for the generation of carbohydrate epitopes for anti-HIV bnAbs. 27707925 1 46 link host-derived 161:172 arg1 glycans 183:189 host-derived N-linked glycans 161:189 host-derived N-linked glycans 161:189 The HIV envelope glycoprotein (Env) is extensively modified with host-derived N-linked glycans. 27707925 14 47 theme HIV 2601:2603 arg1 design 2613:2618 HIV vaccine design 2601:2618 HIV vaccine design 2601:2618 We show that despite this variation in glycan site positioning and frequency over the course of HIV infection, the mannose patch is a conserved feature throughout, making it a stable target for HIV vaccine design. 27707925 5 48 theme longitudinal 726:737 arg1 sequences 743:751 longitudinal Env sequences 726:751 longitudinal Env sequences from a clade C-infected individual (CAP256) 726:795 Here, using longitudinal Env sequences from a clade C-infected individual (CAP256), we measured the impact of the shifting glycan shield during HIV infection on the abundance of oligomannose-type glycans. 27707925 9 49 theme intrinsic 1536:1544 arg1 patch 1554:1558 the intrinsic mannose patch 1532:1558 the intrinsic mannose patch 1532:1558 The persistence of the intrinsic mannose patch over the course of HIV infection further highlights this epitope as an important target for HIV vaccine strategies. 27707925 0 50 theme Patch 59:63 arg1 Persistence 32:42 the Persistence 28:42 the Persistence of the Mannose Patch within an Infected Individual 28:93 HIV-1 Glycan Density Drives the Persistence of the Mannose Patch within an Infected Individual. 27707925 12 51 theme constant 2123:2130 arg1 pressure 2132:2139 constant pressure 2123:2139 constant pressure from the host immune system 2123:2167 This glycan shield is a target for many of the recently isolated anti-HIV bnAbs and is therefore under constant pressure from the host immune system, leading to changes in both glycan site frequency and location. 27707925 0 52 theme HIV-1 0:4 arg1 Density 13:19 HIV-1 Glycan Density 0:19 HIV-1 Glycan Density 0:19 HIV-1 Glycan Density Drives the Persistence of the Mannose Patch within an Infected Individual. 27707925 9 53 theme patch 1554:1558 arg1 persistence 1517:1527 The persistence 1513:1527 The persistence of the intrinsic mannose patch over the course of HIV infection 1513:1591 The persistence of the intrinsic mannose patch over the course of HIV infection further highlights this epitope as an important target for HIV vaccine strategies. 27707925 3 54 theme conserved 384:392 arg1 regions 394:400 conserved regions 384:400 conserved regions of the protein from the immune system 384:438 This extensive glycosylation not only shields conserved regions of the protein from the immune system but also acts as a target for anti-HIV broadly neutralizing antibodies (bnAbs). 27707925 4 55 theme host 539:542 arg1 system 551:556 the host immune system 535:556 the host immune system 535:556 In response to the host immune system, the HIV glycan shield is constantly evolving through mutations affecting both the positions and numbers of potential N-linked glycosylation sites (PNGSs). 27707925 14 56 from variation 2433:2441 arg1 frequency 2474:2482 frequency 2474:2482 frequency 2474:2482 We show that despite this variation in glycan site positioning and frequency over the course of HIV infection, the mannose patch is a conserved feature throughout, making it a stable target for HIV vaccine design. 27707925 14 56 from variation 2433:2441 arg1 positioning 2458:2468 glycan site positioning 2446:2468 glycan site positioning 2446:2468 We show that despite this variation in glycan site positioning and frequency over the course of HIV infection, the mannose patch is a conserved feature throughout, making it a stable target for HIV vaccine design. 27707925 6 57 dep PNGS 1062:1065 arg1 positioning 1078:1088 positioning 1078:1088 positioning 1078:1088 By analyzing the intrinsic mannose patch from a panel of recombinant CAP256 gp120s displaying high protein sequence variability and changes in PNGS number and positioning, we show that the intrinsic mannose patch persists throughout the course of HIV infection and correlates with the number of PNGSs. 27707925 6 57 dep PNGS 1062:1065 arg1 number 1067:1072 number 1067:1072 number 1067:1072 By analyzing the intrinsic mannose patch from a panel of recombinant CAP256 gp120s displaying high protein sequence variability and changes in PNGS number and positioning, we show that the intrinsic mannose patch persists throughout the course of HIV infection and correlates with the number of PNGSs. 27707925 6 57 dep PNGS 1062:1065 arg1 PNGS 1062:1065 PNGS number and positioning 1062:1088 PNGS number and positioning 1062:1088 By analyzing the intrinsic mannose patch from a panel of recombinant CAP256 gp120s displaying high protein sequence variability and changes in PNGS number and positioning, we show that the intrinsic mannose patch persists throughout the course of HIV infection and correlates with the number of PNGSs. 27707925 14 58 theme glycan 2446:2451 arg1 positioning 2458:2468 glycan site positioning 2446:2468 glycan site positioning 2446:2468 We show that despite this variation in glycan site positioning and frequency over the course of HIV infection, the mannose patch is a conserved feature throughout, making it a stable target for HIV vaccine design. 27707925 6 59 theme sequence 1026:1033 arg1 variability 1035:1045 high protein sequence variability 1013:1045 high protein sequence variability 1013:1045 By analyzing the intrinsic mannose patch from a panel of recombinant CAP256 gp120s displaying high protein sequence variability and changes in PNGS number and positioning, we show that the intrinsic mannose patch persists throughout the course of HIV infection and correlates with the number of PNGSs. 27707925 5 60 dep glycan 837:842 arg1 shield 844:849 shield 844:849 shield during HIV infection 844:870 Here, using longitudinal Env sequences from a clade C-infected individual (CAP256), we measured the impact of the shifting glycan shield during HIV infection on the abundance of oligomannose-type glycans. 27707925 5 61 theme C-infected 766:775 arg1 individual 777:786 a clade C-infected individual 758:786 a clade C-infected individual (CAP256) 758:795 Here, using longitudinal Env sequences from a clade C-infected individual (CAP256), we measured the impact of the shifting glycan shield during HIV infection on the abundance of oligomannose-type glycans. 27707925 5 61 theme C-infected 766:775 arg1 CAP256 789:794 CAP256 789:794 CAP256 789:794 Here, using longitudinal Env sequences from a clade C-infected individual (CAP256), we measured the impact of the shifting glycan shield during HIV infection on the abundance of oligomannose-type glycans. 27707925 6 62 theme high 1013:1016 arg1 variability 1035:1045 high protein sequence variability 1013:1045 high protein sequence variability 1013:1045 By analyzing the intrinsic mannose patch from a panel of recombinant CAP256 gp120s displaying high protein sequence variability and changes in PNGS number and positioning, we show that the intrinsic mannose patch persists throughout the course of HIV infection and correlates with the number of PNGSs. 27707925 3 63 theme protein 409:415 arg1 regions 394:400 conserved regions 384:400 conserved regions of the protein from the immune system 384:438 This extensive glycosylation not only shields conserved regions of the protein from the immune system but also acts as a target for anti-HIV broadly neutralizing antibodies (bnAbs). 27707925 11 64 gly glycoprotein 1905:1916 arg1 glycoprotein 1905:1916 The HIV envelope glycoprotein 1888:1916 The HIV envelope glycoprotein (Env) 1888:1922 The HIV envelope glycoprotein (Env) is covered in an array of host-derived N-linked glycans often referred to as the glycan shield. 27707925 11 64 gly glycoprotein 1905:1916 arg1 Env 1919:1921 Env 1919:1921 Env 1919:1921 The HIV envelope glycoprotein (Env) is covered in an array of host-derived N-linked glycans often referred to as the glycan shield. 27707925 11 65 link N-linked 1963:1970 arg1 glycans 1972:1978 host-derived N-linked glycans 1950:1978 host-derived N-linked glycans often referred to as the glycan shield 1950:2017 The HIV envelope glycoprotein (Env) is covered in an array of host-derived N-linked glycans often referred to as the glycan shield. 27707925 3 66 theme neutralizing 487:498 arg1 bnAbs 512:516 bnAbs 512:516 bnAbs 512:516 This extensive glycosylation not only shields conserved regions of the protein from the immune system but also acts as a target for anti-HIV broadly neutralizing antibodies (bnAbs). 27707925 3 66 theme neutralizing 487:498 arg1 antibodies 500:509 anti-HIV broadly neutralizing antibodies 470:509 anti-HIV broadly neutralizing antibodies (bnAbs) 470:517 This extensive glycosylation not only shields conserved regions of the protein from the immune system but also acts as a target for anti-HIV broadly neutralizing antibodies (bnAbs). 27707925 9 67 theme infection 1583:1591 arg1 course 1569:1574 the course 1565:1574 the course of HIV infection 1565:1591 The persistence of the intrinsic mannose patch over the course of HIV infection further highlights this epitope as an important target for HIV vaccine strategies. 27707925 7 68 theme density 1247:1253 arg1 effect 1226:1231 This effect 1221:1231 This effect of the glycan density on the processing state 1221:1277 This effect of the glycan density on the processing state was also supported by the analysis of a cross-clade panel of recombinant gp120 glycoproteins. 27707925 3 69 theme anti-HIV 470:477 arg1 bnAbs 512:516 bnAbs 512:516 bnAbs 512:516 This extensive glycosylation not only shields conserved regions of the protein from the immune system but also acts as a target for anti-HIV broadly neutralizing antibodies (bnAbs). 27707925 3 69 theme anti-HIV 470:477 arg1 antibodies 500:509 anti-HIV broadly neutralizing antibodies 470:509 anti-HIV broadly neutralizing antibodies (bnAbs) 470:517 This extensive glycosylation not only shields conserved regions of the protein from the immune system but also acts as a target for anti-HIV broadly neutralizing antibodies (bnAbs). 27707925 1 70 mod modified 147:154 arg1 glycoprotein 113:124 The HIV envelope glycoprotein 96:124 The HIV envelope glycoprotein (Env) 96:130 The HIV envelope glycoprotein (Env) is extensively modified with host-derived N-linked glycans. 27707925 1 70 mod modified 147:154 arg3 glycans 183:189 host-derived N-linked glycans 161:189 host-derived N-linked glycans 161:189 The HIV envelope glycoprotein (Env) is extensively modified with host-derived N-linked glycans. 27707925 1 70 mod modified 147:154 arg1 Env 127:129 Env 127:129 Env 127:129 The HIV envelope glycoprotein (Env) is extensively modified with host-derived N-linked glycans. 27707925 12 71 theme anti-HIV 2085:2092 arg1 bnAbs 2094:2098 the recently isolated anti-HIV bnAbs 2063:2098 the recently isolated anti-HIV bnAbs 2063:2098 This glycan shield is a target for many of the recently isolated anti-HIV bnAbs and is therefore under constant pressure from the host immune system, leading to changes in both glycan site frequency and location. 27707925 10 72 theme vaccine 1710:1716 arg1 Development 1688:1698 Development 1688:1698 Development of an HIV vaccine 1688:1716 IMPORTANCE: Development of an HIV vaccine is critical for control of the HIV pandemic, and elicitation of broadly neutralizing antibodies (bnAbs) is likely to be a key component of a successful vaccine response. 27707925 4 73 dep positions 641:649 arg1 the 637:639 the 637:639 the 637:639 In response to the host immune system, the HIV glycan shield is constantly evolving through mutations affecting both the positions and numbers of potential N-linked glycosylation sites (PNGSs). 27707925 14 74 theme conserved 2541:2549 arg1 patch 2530:2534 the mannose patch 2518:2534 the mannose patch 2518:2534 We show that despite this variation in glycan site positioning and frequency over the course of HIV infection, the mannose patch is a conserved feature throughout, making it a stable target for HIV vaccine design. 27707925 14 74 theme conserved 2541:2549 arg1 feature 2551:2557 a conserved feature 2539:2557 a conserved feature throughout 2539:2568 We show that despite this variation in glycan site positioning and frequency over the course of HIV infection, the mannose patch is a conserved feature throughout, making it a stable target for HIV vaccine design. 27707925 11 75 dep glycan 2005:2010 arg1 shield 2012:2017 shield 2012:2017 shield 2012:2017 The HIV envelope glycoprotein (Env) is covered in an array of host-derived N-linked glycans often referred to as the glycan shield. 27707925 10 76 theme pandemic 1753:1760 arg1 control 1734:1740 control 1734:1740 control of the HIV pandemic 1734:1760 IMPORTANCE: Development of an HIV vaccine is critical for control of the HIV pandemic, and elicitation of broadly neutralizing antibodies (bnAbs) is likely to be a key component of a successful vaccine response. 27707925 14 77 theme stable 2583:2588 arg1 target 2590:2595 a stable target 2581:2595 it a stable target for HIV vaccine design 2578:2618 We show that despite this variation in glycan site positioning and frequency over the course of HIV infection, the mannose patch is a conserved feature throughout, making it a stable target for HIV vaccine design. 27707925 5 78 theme glycan 837:842 arg1 impact 814:819 the impact 810:819 the impact of the shifting glycan shield during HIV infection on the abundance of oligomannose-type glycans 810:916 Here, using longitudinal Env sequences from a clade C-infected individual (CAP256), we measured the impact of the shifting glycan shield during HIV infection on the abundance of oligomannose-type glycans. 27707925 9 79 theme HIV 1652:1654 arg1 strategies 1664:1673 HIV vaccine strategies 1652:1673 HIV vaccine strategies 1652:1673 The persistence of the intrinsic mannose patch over the course of HIV infection further highlights this epitope as an important target for HIV vaccine strategies. 27707925 10 80 theme vaccine 1870:1876 arg1 response 1878:1885 a successful vaccine response 1857:1885 a successful vaccine response 1857:1885 IMPORTANCE: Development of an HIV vaccine is critical for control of the HIV pandemic, and elicitation of broadly neutralizing antibodies (bnAbs) is likely to be a key component of a successful vaccine response. 27707925 2 81 theme oligomannose-type 311:327 arg1 glycans 329:335 numerous underprocessed oligomannose-type glycans 287:335 numerous underprocessed oligomannose-type glycans 287:335 The high density of glycosylation on the viral spike limits enzymatic processing, resulting in numerous underprocessed oligomannose-type glycans. 27707925 1 82 theme host-derived 161:172 arg1 glycans 183:189 host-derived N-linked glycans 161:189 host-derived N-linked glycans 161:189 The HIV envelope glycoprotein (Env) is extensively modified with host-derived N-linked glycans. 27707925 10 83 theme key 1840:1842 arg1 elicitation 1767:1777 elicitation 1767:1777 elicitation of broadly neutralizing antibodies (bnAbs) 1767:1820 IMPORTANCE: Development of an HIV vaccine is critical for control of the HIV pandemic, and elicitation of broadly neutralizing antibodies (bnAbs) is likely to be a key component of a successful vaccine response. 27707925 10 83 theme key 1840:1842 arg1 component 1844:1852 a key component 1838:1852 a key component of a successful vaccine response 1838:1885 IMPORTANCE: Development of an HIV vaccine is critical for control of the HIV pandemic, and elicitation of broadly neutralizing antibodies (bnAbs) is likely to be a key component of a successful vaccine response. 27707925 13 84 theme virus 2382:2386 arg1 processing 2315:2324 the eventual processing 2302:2324 the eventual processing of glycans on the HIV Env 2302:2350 This study aimed to determine whether these genetic changes impacted the eventual processing of glycans on the HIV Env and the susceptibility of the virus to neutralization. 27707925 13 84 theme virus 2382:2386 arg1 susceptibility 2360:2373 the susceptibility 2356:2373 the susceptibility of the virus to neutralization 2356:2404 This study aimed to determine whether these genetic changes impacted the eventual processing of glycans on the HIV Env and the susceptibility of the virus to neutralization. 27707925 12 85 dep glycan 2025:2030 arg1 shield 2032:2037 shield 2032:2037 shield 2032:2037 This glycan shield is a target for many of the recently isolated anti-HIV bnAbs and is therefore under constant pressure from the host immune system, leading to changes in both glycan site frequency and location. 27707925 2 86 theme numerous 287:294 arg1 glycans 329:335 numerous underprocessed oligomannose-type glycans 287:335 numerous underprocessed oligomannose-type glycans 287:335 The high density of glycosylation on the viral spike limits enzymatic processing, resulting in numerous underprocessed oligomannose-type glycans. 27707925 10 87 theme HIV 1749:1751 arg1 pandemic 1753:1760 the HIV pandemic 1745:1760 the HIV pandemic 1745:1760 IMPORTANCE: Development of an HIV vaccine is critical for control of the HIV pandemic, and elicitation of broadly neutralizing antibodies (bnAbs) is likely to be a key component of a successful vaccine response. 27707925 6 88 theme intrinsic 936:944 arg1 patch 954:958 the intrinsic mannose patch 932:958 the intrinsic mannose patch 932:958 By analyzing the intrinsic mannose patch from a panel of recombinant CAP256 gp120s displaying high protein sequence variability and changes in PNGS number and positioning, we show that the intrinsic mannose patch persists throughout the course of HIV infection and correlates with the number of PNGSs. 27707925 6 89 theme intrinsic 1108:1116 arg1 patch 1126:1130 the intrinsic mannose patch 1104:1130 the intrinsic mannose patch 1104:1130 By analyzing the intrinsic mannose patch from a panel of recombinant CAP256 gp120s displaying high protein sequence variability and changes in PNGS number and positioning, we show that the intrinsic mannose patch persists throughout the course of HIV infection and correlates with the number of PNGSs. 27707925 4 90 dep glycan 567:572 arg1 shield 574:579 shield 574:579 shield 574:579 In response to the host immune system, the HIV glycan shield is constantly evolving through mutations affecting both the positions and numbers of potential N-linked glycosylation sites (PNGSs). 27707925 8 91 theme glycan 1431:1436 arg1 clustering 1438:1447 glycan clustering 1431:1447 glycan clustering 1431:1447 Together, these observations underscore the importance of glycan clustering for the generation of carbohydrate epitopes for anti-HIV bnAbs. 27707925 7 92 theme recombinant 1340:1350 arg1 glycoproteins 1358:1370 recombinant gp120 glycoproteins 1340:1370 recombinant gp120 glycoproteins 1340:1370 This effect of the glycan density on the processing state was also supported by the analysis of a cross-clade panel of recombinant gp120 glycoproteins. 27707925 11 93 theme HIV 1892:1894 arg1 glycoprotein 1905:1916 The HIV envelope glycoprotein 1888:1916 The HIV envelope glycoprotein (Env) 1888:1922 The HIV envelope glycoprotein (Env) is covered in an array of host-derived N-linked glycans often referred to as the glycan shield. 27707925 11 93 theme HIV 1892:1894 arg1 Env 1919:1921 Env 1919:1921 Env 1919:1921 The HIV envelope glycoprotein (Env) is covered in an array of host-derived N-linked glycans often referred to as the glycan shield. 27707925 1 94 theme HIV 100:102 arg1 glycoprotein 113:124 The HIV envelope glycoprotein 96:124 The HIV envelope glycoprotein (Env) 96:130 The HIV envelope glycoprotein (Env) is extensively modified with host-derived N-linked glycans. 27707925 1 94 theme HIV 100:102 arg1 Env 127:129 Env 127:129 Env 127:129 The HIV envelope glycoprotein (Env) is extensively modified with host-derived N-linked glycans. 27707925 12 95 theme glycan 2197:2202 arg1 frequency 2209:2217 glycan site frequency 2197:2217 glycan site frequency 2197:2217 This glycan shield is a target for many of the recently isolated anti-HIV bnAbs and is therefore under constant pressure from the host immune system, leading to changes in both glycan site frequency and location. 27707925 14 96 theme infection 2507:2515 arg1 course 2493:2498 the course 2489:2498 the course of HIV infection 2489:2515 We show that despite this variation in glycan site positioning and frequency over the course of HIV infection, the mannose patch is a conserved feature throughout, making it a stable target for HIV vaccine design. 27707925 7 97 theme panel 1331:1335 arg1 analysis 1305:1312 the analysis 1301:1312 the analysis of a cross-clade panel of recombinant gp120 glycoproteins 1301:1370 This effect of the glycan density on the processing state was also supported by the analysis of a cross-clade panel of recombinant gp120 glycoproteins. 27707925 4 98 gly glycosylation 685:697 arg2 PNGSs 706:710 PNGSs 706:710 PNGSs 706:710 In response to the host immune system, the HIV glycan shield is constantly evolving through mutations affecting both the positions and numbers of potential N-linked glycosylation sites (PNGSs). 27707925 4 98 gly glycosylation 685:697 arg2 sites 699:703 potential N-linked glycosylation sites 666:703 potential N-linked glycosylation sites (PNGSs) 666:711 In response to the host immune system, the HIV glycan shield is constantly evolving through mutations affecting both the positions and numbers of potential N-linked glycosylation sites (PNGSs). 27707925 6 99 theme mannose 1118:1124 arg1 patch 1126:1130 the intrinsic mannose patch 1104:1130 the intrinsic mannose patch 1104:1130 By analyzing the intrinsic mannose patch from a panel of recombinant CAP256 gp120s displaying high protein sequence variability and changes in PNGS number and positioning, we show that the intrinsic mannose patch persists throughout the course of HIV infection and correlates with the number of PNGSs. 27707925 13 100 theme eventual 2306:2313 arg1 processing 2315:2324 the eventual processing 2302:2324 the eventual processing of glycans on the HIV Env 2302:2350 This study aimed to determine whether these genetic changes impacted the eventual processing of glycans on the HIV Env and the susceptibility of the virus to neutralization. 27707925 13 101 from processing 2315:2324 arg1 Env 2348:2350 the HIV Env 2340:2350 the HIV Env 2340:2350 This study aimed to determine whether these genetic changes impacted the eventual processing of glycans on the HIV Env and the susceptibility of the virus to neutralization. 27707925 5 102 theme Env 739:741 arg1 sequences 743:751 longitudinal Env sequences 726:751 longitudinal Env sequences from a clade C-infected individual (CAP256) 726:795 Here, using longitudinal Env sequences from a clade C-infected individual (CAP256), we measured the impact of the shifting glycan shield during HIV infection on the abundance of oligomannose-type glycans. 27707925 2 103 theme viral 233:237 arg1 spike 239:243 the viral spike 229:243 the viral spike 229:243 The high density of glycosylation on the viral spike limits enzymatic processing, resulting in numerous underprocessed oligomannose-type glycans. 27707925 6 104 theme CAP256 988:993 arg1 gp120s 995:1000 recombinant CAP256 gp120s 976:1000 recombinant CAP256 gp120s displaying high protein sequence variability 976:1045 By analyzing the intrinsic mannose patch from a panel of recombinant CAP256 gp120s displaying high protein sequence variability and changes in PNGS number and positioning, we show that the intrinsic mannose patch persists throughout the course of HIV infection and correlates with the number of PNGSs. 27707925 3 105 theme extensive 343:351 arg1 target 459:464 a target 457:464 a target for anti-HIV broadly neutralizing antibodies (bnAbs) 457:517 This extensive glycosylation not only shields conserved regions of the protein from the immune system but also acts as a target for anti-HIV broadly neutralizing antibodies (bnAbs). 27707925 3 105 theme extensive 343:351 arg1 glycosylation 353:365 This extensive glycosylation 338:365 This extensive glycosylation 338:365 This extensive glycosylation not only shields conserved regions of the protein from the immune system but also acts as a target for anti-HIV broadly neutralizing antibodies (bnAbs). 27707925 8 106 theme carbohydrate 1471:1482 arg1 epitopes 1484:1491 carbohydrate epitopes 1471:1491 carbohydrate epitopes for anti-HIV bnAbs 1471:1510 Together, these observations underscore the importance of glycan clustering for the generation of carbohydrate epitopes for anti-HIV bnAbs. 27707925 6 107 theme HIV 1166:1168 arg1 infection 1170:1178 HIV infection 1166:1178 HIV infection 1166:1178 By analyzing the intrinsic mannose patch from a panel of recombinant CAP256 gp120s displaying high protein sequence variability and changes in PNGS number and positioning, we show that the intrinsic mannose patch persists throughout the course of HIV infection and correlates with the number of PNGSs. 27707925 4 108 theme potential 666:674 arg1 PNGSs 706:710 PNGSs 706:710 PNGSs 706:710 In response to the host immune system, the HIV glycan shield is constantly evolving through mutations affecting both the positions and numbers of potential N-linked glycosylation sites (PNGSs). 27707925 4 108 theme potential 666:674 arg1 sites 699:703 potential N-linked glycosylation sites 666:703 potential N-linked glycosylation sites (PNGSs) 666:711 In response to the host immune system, the HIV glycan shield is constantly evolving through mutations affecting both the positions and numbers of potential N-linked glycosylation sites (PNGSs). 27707925 12 109 theme site 2204:2207 arg1 frequency 2209:2217 glycan site frequency 2197:2217 glycan site frequency 2197:2217 This glycan shield is a target for many of the recently isolated anti-HIV bnAbs and is therefore under constant pressure from the host immune system, leading to changes in both glycan site frequency and location. 27707925 4 110 theme glycosylation 685:697 arg1 PNGSs 706:710 PNGSs 706:710 PNGSs 706:710 In response to the host immune system, the HIV glycan shield is constantly evolving through mutations affecting both the positions and numbers of potential N-linked glycosylation sites (PNGSs). 27707925 4 110 theme glycosylation 685:697 arg1 sites 699:703 potential N-linked glycosylation sites 666:703 potential N-linked glycosylation sites (PNGSs) 666:711 In response to the host immune system, the HIV glycan shield is constantly evolving through mutations affecting both the positions and numbers of potential N-linked glycosylation sites (PNGSs). 27707925 10 111 dep critical 1721:1728 arg1 IMPORTANCE 1676:1685 IMPORTANCE 1676:1685 IMPORTANCE 1676:1685 IMPORTANCE: Development of an HIV vaccine is critical for control of the HIV pandemic, and elicitation of broadly neutralizing antibodies (bnAbs) is likely to be a key component of a successful vaccine response. 27707925 12 112 from changes 2181:2187 arg1 location 2223:2230 location 2223:2230 location 2223:2230 This glycan shield is a target for many of the recently isolated anti-HIV bnAbs and is therefore under constant pressure from the host immune system, leading to changes in both glycan site frequency and location. 27707925 12 112 from changes 2181:2187 arg1 frequency 2209:2217 glycan site frequency 2197:2217 glycan site frequency 2197:2217 This glycan shield is a target for many of the recently isolated anti-HIV bnAbs and is therefore under constant pressure from the host immune system, leading to changes in both glycan site frequency and location. 27707925 7 113 theme glycoproteins 1358:1370 arg1 panel 1331:1335 a cross-clade panel 1317:1335 a cross-clade panel of recombinant gp120 glycoproteins 1317:1370 This effect of the glycan density on the processing state was also supported by the analysis of a cross-clade panel of recombinant gp120 glycoproteins. 27707925 10 114 theme neutralizing 1790:1801 arg1 bnAbs 1815:1819 bnAbs 1815:1819 bnAbs 1815:1819 IMPORTANCE: Development of an HIV vaccine is critical for control of the HIV pandemic, and elicitation of broadly neutralizing antibodies (bnAbs) is likely to be a key component of a successful vaccine response. 27707925 10 114 theme neutralizing 1790:1801 arg1 antibodies 1803:1812 broadly neutralizing antibodies 1782:1812 broadly neutralizing antibodies (bnAbs) 1782:1820 IMPORTANCE: Development of an HIV vaccine is critical for control of the HIV pandemic, and elicitation of broadly neutralizing antibodies (bnAbs) is likely to be a key component of a successful vaccine response. 27707925 4 115 dep system 551:556 arg1 response 523:530 response 523:530 response 523:530 In response to the host immune system, the HIV glycan shield is constantly evolving through mutations affecting both the positions and numbers of potential N-linked glycosylation sites (PNGSs). 27707925 2 116 from density 201:207 arg1 spike 239:243 the viral spike 229:243 the viral spike 229:243 The high density of glycosylation on the viral spike limits enzymatic processing, resulting in numerous underprocessed oligomannose-type glycans. 27707925 1 117 link N-linked 174:181 arg1 glycans 183:189 host-derived N-linked glycans 161:189 host-derived N-linked glycans 161:189 The HIV envelope glycoprotein (Env) is extensively modified with host-derived N-linked glycans. 27707925 12 118 theme immune 2155:2160 arg1 system 2162:2167 the host immune system 2146:2167 the host immune system 2146:2167 This glycan shield is a target for many of the recently isolated anti-HIV bnAbs and is therefore under constant pressure from the host immune system, leading to changes in both glycan site frequency and location. 27707925 0 119 theme Glycan 6:11 arg1 Density 13:19 HIV-1 Glycan Density 0:19 HIV-1 Glycan Density 0:19 HIV-1 Glycan Density Drives the Persistence of the Mannose Patch within an Infected Individual. 27707925 14 120 dep it 2578:2579 arg1 target 2590:2595 a stable target 2581:2595 it a stable target for HIV vaccine design 2578:2618 We show that despite this variation in glycan site positioning and frequency over the course of HIV infection, the mannose patch is a conserved feature throughout, making it a stable target for HIV vaccine design. 27707925 5 121 theme glycans 910:916 arg1 abundance 879:887 the abundance 875:887 the abundance of oligomannose-type glycans 875:916 Here, using longitudinal Env sequences from a clade C-infected individual (CAP256), we measured the impact of the shifting glycan shield during HIV infection on the abundance of oligomannose-type glycans. 27707925 3 122 from regions 394:400 arg1 system 433:438 the immune system 422:438 the immune system 422:438 This extensive glycosylation not only shields conserved regions of the protein from the immune system but also acts as a target for anti-HIV broadly neutralizing antibodies (bnAbs). 27707925 4 123 theme immune 544:549 arg1 system 551:556 the host immune system 535:556 the host immune system 535:556 In response to the host immune system, the HIV glycan shield is constantly evolving through mutations affecting both the positions and numbers of potential N-linked glycosylation sites (PNGSs). 27707925 6 124 from panel 967:971 arg1 positioning 1078:1088 positioning 1078:1088 positioning 1078:1088 By analyzing the intrinsic mannose patch from a panel of recombinant CAP256 gp120s displaying high protein sequence variability and changes in PNGS number and positioning, we show that the intrinsic mannose patch persists throughout the course of HIV infection and correlates with the number of PNGSs. 27707925 6 124 from panel 967:971 arg1 number 1067:1072 number 1067:1072 number 1067:1072 By analyzing the intrinsic mannose patch from a panel of recombinant CAP256 gp120s displaying high protein sequence variability and changes in PNGS number and positioning, we show that the intrinsic mannose patch persists throughout the course of HIV infection and correlates with the number of PNGSs. 27707925 6 124 from panel 967:971 arg1 PNGS 1062:1065 PNGS number and positioning 1062:1088 PNGS number and positioning 1062:1088 By analyzing the intrinsic mannose patch from a panel of recombinant CAP256 gp120s displaying high protein sequence variability and changes in PNGS number and positioning, we show that the intrinsic mannose patch persists throughout the course of HIV infection and correlates with the number of PNGSs. 27707925 11 125 theme host-derived 1950:1961 arg1 glycans 1972:1978 host-derived N-linked glycans 1950:1978 host-derived N-linked glycans often referred to as the glycan shield 1950:2017 The HIV envelope glycoprotein (Env) is covered in an array of host-derived N-linked glycans often referred to as the glycan shield. 27707925 13 126 theme glycans 2329:2335 arg1 processing 2315:2324 the eventual processing 2302:2324 the eventual processing of glycans on the HIV Env 2302:2350 This study aimed to determine whether these genetic changes impacted the eventual processing of glycans on the HIV Env and the susceptibility of the virus to neutralization. 27707925 13 126 theme glycans 2329:2335 arg1 susceptibility 2360:2373 the susceptibility 2356:2373 the susceptibility of the virus to neutralization 2356:2404 This study aimed to determine whether these genetic changes impacted the eventual processing of glycans on the HIV Env and the susceptibility of the virus to neutralization. 27707925 7 127 theme processing 1262:1271 arg1 state 1273:1277 the processing state 1258:1277 the processing state 1258:1277 This effect of the glycan density on the processing state was also supported by the analysis of a cross-clade panel of recombinant gp120 glycoproteins. 27707925 5 128 theme clade 760:764 arg1 individual 777:786 a clade C-infected individual 758:786 a clade C-infected individual (CAP256) 758:795 Here, using longitudinal Env sequences from a clade C-infected individual (CAP256), we measured the impact of the shifting glycan shield during HIV infection on the abundance of oligomannose-type glycans. 27707925 5 128 theme clade 760:764 arg1 CAP256 789:794 CAP256 789:794 CAP256 789:794 Here, using longitudinal Env sequences from a clade C-infected individual (CAP256), we measured the impact of the shifting glycan shield during HIV infection on the abundance of oligomannose-type glycans. 27707925 6 129 theme protein 1018:1024 arg1 variability 1035:1045 high protein sequence variability 1013:1045 high protein sequence variability 1013:1045 By analyzing the intrinsic mannose patch from a panel of recombinant CAP256 gp120s displaying high protein sequence variability and changes in PNGS number and positioning, we show that the intrinsic mannose patch persists throughout the course of HIV infection and correlates with the number of PNGSs. 27707925 3 130 theme immune 426:431 arg1 system 433:438 the immune system 422:438 the immune system 422:438 This extensive glycosylation not only shields conserved regions of the protein from the immune system but also acts as a target for anti-HIV broadly neutralizing antibodies (bnAbs). 27707925 12 131 theme bnAbs 2094:2098 arg1 many 2055:2058 many 2055:2058 many 2055:2058 This glycan shield is a target for many of the recently isolated anti-HIV bnAbs and is therefore under constant pressure from the host immune system, leading to changes in both glycan site frequency and location. 27707925 12 131 theme bnAbs 2094:2098 arg1 bnAbs 2094:2098 the recently isolated anti-HIV bnAbs 2063:2098 the recently isolated anti-HIV bnAbs 2063:2098 This glycan shield is a target for many of the recently isolated anti-HIV bnAbs and is therefore under constant pressure from the host immune system, leading to changes in both glycan site frequency and location. 27707925 9 132 theme HIV 1579:1581 arg1 infection 1583:1591 HIV infection 1579:1591 HIV infection 1579:1591 The persistence of the intrinsic mannose patch over the course of HIV infection further highlights this epitope as an important target for HIV vaccine strategies. 27707925 7 133 theme glycan 1240:1245 arg1 density 1247:1253 the glycan density 1236:1253 the glycan density 1236:1253 This effect of the glycan density on the processing state was also supported by the analysis of a cross-clade panel of recombinant gp120 glycoproteins. 27707925 2 134 theme high 196:199 arg1 density 201:207 The high density 192:207 The high density of glycosylation on the viral spike 192:243 The high density of glycosylation on the viral spike limits enzymatic processing, resulting in numerous underprocessed oligomannose-type glycans. 27707925 13 135 theme genetic 2277:2283 arg1 changes 2285:2291 these genetic changes 2271:2291 these genetic changes 2271:2291 This study aimed to determine whether these genetic changes impacted the eventual processing of glycans on the HIV Env and the susceptibility of the virus to neutralization. 27707925 13 136 from susceptibility 2360:2373 arg1 Env 2348:2350 the HIV Env 2340:2350 the HIV Env 2340:2350 This study aimed to determine whether these genetic changes impacted the eventual processing of glycans on the HIV Env and the susceptibility of the virus to neutralization. 27707925 3 137 from system 433:438 arg1 regions 394:400 conserved regions 384:400 conserved regions of the protein from the immune system 384:438 This extensive glycosylation not only shields conserved regions of the protein from the immune system but also acts as a target for anti-HIV broadly neutralizing antibodies (bnAbs). 27707925 3 137 from system 433:438 arg1 protein 409:415 the protein 405:415 the protein from the immune system 405:438 This extensive glycosylation not only shields conserved regions of the protein from the immune system but also acts as a target for anti-HIV broadly neutralizing antibodies (bnAbs). 27707925 3 138 theme broadly 479:485 arg1 bnAbs 512:516 bnAbs 512:516 bnAbs 512:516 This extensive glycosylation not only shields conserved regions of the protein from the immune system but also acts as a target for anti-HIV broadly neutralizing antibodies (bnAbs). 27707925 3 138 theme broadly 479:485 arg1 antibodies 500:509 anti-HIV broadly neutralizing antibodies 470:509 anti-HIV broadly neutralizing antibodies (bnAbs) 470:517 This extensive glycosylation not only shields conserved regions of the protein from the immune system but also acts as a target for anti-HIV broadly neutralizing antibodies (bnAbs). 27707925 10 139 theme successful 1859:1868 arg1 response 1878:1885 a successful vaccine response 1857:1885 a successful vaccine response 1857:1885 IMPORTANCE: Development of an HIV vaccine is critical for control of the HIV pandemic, and elicitation of broadly neutralizing antibodies (bnAbs) is likely to be a key component of a successful vaccine response. 27707925 12 140 theme isolated 2076:2083 arg1 bnAbs 2094:2098 the recently isolated anti-HIV bnAbs 2063:2098 the recently isolated anti-HIV bnAbs 2063:2098 This glycan shield is a target for many of the recently isolated anti-HIV bnAbs and is therefore under constant pressure from the host immune system, leading to changes in both glycan site frequency and location. 27707925 10 141 theme HIV 1706:1708 arg1 vaccine 1710:1716 an HIV vaccine 1703:1716 an HIV vaccine 1703:1716 IMPORTANCE: Development of an HIV vaccine is critical for control of the HIV pandemic, and elicitation of broadly neutralizing antibodies (bnAbs) is likely to be a key component of a successful vaccine response. 27888602 7 0 theme lactosaminyl 1487:1498 arg1 synthesis 1507:1515 lactosaminyl glycan synthesis 1487:1515 lactosaminyl glycan synthesis 1487:1515 The finding that hMSCs from both source tissues each lack native E-selectin ligand expression prompted examination of the expression of glycosyltransferases that direct lactosaminyl glycan synthesis. 27888602 6 1 theme HCELL 1192:1196 arg1 expression 1178:1187 expression 1178:1187 expression of HCELL on both BM-hMSCs and A-hMSCs 1178:1225 Moreover, treatment with the α(1,3)-fucosyltransferase-FTVII also generated expression of HCELL on both BM-hMSCs and A-hMSCs, with sLeX decorations created on N-linked glycans of the "standard" CD44 (CD44s) isoform. 27888602 9 2 theme cells 1938:1942 arg1 glycosignature 1914:1927 a CD44 glycosignature 1907:1927 a CD44 glycosignature of these cells 1907:1942 Collectively, these data indicate that assembly of a sialyllactosaminyl-decorated CD44s glycovariant is a conserved feature of hMSCs derived from adipose tissue and marrow, thus identifying a CD44 glycosignature of these cells and supporting the applicability of cell surface α(1,3)-fucosylation in programming migration of systemically administered A-hMSCs to sites of tissue injury/inflammation. 27888602 7 3 theme ligand 1394:1399 arg1 expression 1401:1410 native E-selectin ligand expression 1376:1410 native E-selectin ligand expression 1376:1410 The finding that hMSCs from both source tissues each lack native E-selectin ligand expression prompted examination of the expression of glycosyltransferases that direct lactosaminyl glycan synthesis. 27888602 7 4 theme native 1376:1381 arg1 ligand 1394:1399 native E-selectin ligand 1376:1399 native E-selectin ligand expression 1376:1410 The finding that hMSCs from both source tissues each lack native E-selectin ligand expression prompted examination of the expression of glycosyltransferases that direct lactosaminyl glycan synthesis. 27888602 2 5 theme endothelial 301:311 arg1 capacity 321:328 endothelial binding capacity 301:328 endothelial binding capacity 301:328 hMSCs derived from bone marrow (BM-hMSCs) natively lack endothelial binding capacity, but express a CD44 glycovariant containing N-linked sialyllactosamines that can be α(1,3)-fucosylated using fucosyltransferase-VI (FTVI) to enforce sLeX decorations, thereby creating hematopoietic cell E-/L-selectin ligand (HCELL). 27888602 9 6 theme cell 1980:1983 arg1 -fucosylation 1999:2011 cell surface α(1,3)-fucosylation 1980:2011 cell surface α(1,3)-fucosylation 1980:2011 Collectively, these data indicate that assembly of a sialyllactosaminyl-decorated CD44s glycovariant is a conserved feature of hMSCs derived from adipose tissue and marrow, thus identifying a CD44 glycosignature of these cells and supporting the applicability of cell surface α(1,3)-fucosylation in programming migration of systemically administered A-hMSCs to sites of tissue injury/inflammation. 27888602 6 7 theme isoform 1309:1315 arg1 glycans 1270:1276 N-linked glycans 1261:1276 N-linked glycans of the "standard" CD44 (CD44s) isoform 1261:1315 Moreover, treatment with the α(1,3)-fucosyltransferase-FTVII also generated expression of HCELL on both BM-hMSCs and A-hMSCs, with sLeX decorations created on N-linked glycans of the "standard" CD44 (CD44s) isoform. 27888602 7 8 theme source 1351:1356 arg1 tissues 1358:1364 both source tissues 1346:1364 both source tissues 1346:1364 The finding that hMSCs from both source tissues each lack native E-selectin ligand expression prompted examination of the expression of glycosyltransferases that direct lactosaminyl glycan synthesis. 27888602 9 9 theme α 1993:1993 arg1 -fucosylation 1999:2011 cell surface α(1,3)-fucosylation 1980:2011 cell surface α(1,3)-fucosylation 1980:2011 Collectively, these data indicate that assembly of a sialyllactosaminyl-decorated CD44s glycovariant is a conserved feature of hMSCs derived from adipose tissue and marrow, thus identifying a CD44 glycosignature of these cells and supporting the applicability of cell surface α(1,3)-fucosylation in programming migration of systemically administered A-hMSCs to sites of tissue injury/inflammation. 27888602 6 10 theme CD44s 1302:1306 arg1 isoform 1309:1315 the "standard" CD44 (CD44s) isoform 1281:1315 the "standard" CD44 (CD44s) isoform 1281:1315 Moreover, treatment with the α(1,3)-fucosyltransferase-FTVII also generated expression of HCELL on both BM-hMSCs and A-hMSCs, with sLeX decorations created on N-linked glycans of the "standard" CD44 (CD44s) isoform. 27888602 7 11 dep hMSCs 1335:1339 arg1 lack 1371:1374 lack 1371:1374 lack native E-selectin ligand expression 1371:1410 The finding that hMSCs from both source tissues each lack native E-selectin ligand expression prompted examination of the expression of glycosyltransferases that direct lactosaminyl glycan synthesis. 27888602 9 12 theme 1,3 1995:1997 arg1 -fucosylation 1999:2011 cell surface α(1,3)-fucosylation 1980:2011 cell surface α(1,3)-fucosylation 1980:2011 Collectively, these data indicate that assembly of a sialyllactosaminyl-decorated CD44s glycovariant is a conserved feature of hMSCs derived from adipose tissue and marrow, thus identifying a CD44 glycosignature of these cells and supporting the applicability of cell surface α(1,3)-fucosylation in programming migration of systemically administered A-hMSCs to sites of tissue injury/inflammation. 27888602 6 13 theme CD44 1296:1299 arg1 isoform 1309:1315 the "standard" CD44 (CD44s) isoform 1281:1315 the "standard" CD44 (CD44s) isoform 1281:1315 Moreover, treatment with the α(1,3)-fucosyltransferase-FTVII also generated expression of HCELL on both BM-hMSCs and A-hMSCs, with sLeX decorations created on N-linked glycans of the "standard" CD44 (CD44s) isoform. 27888602 3 14 theme potent 589:594 arg1 adhesion 612:619 potent shear-resistant adhesion 589:619 potent shear-resistant adhesion of circulating cells to endothelial beds expressing E-selectin 589:682 HCELL expression programs potent shear-resistant adhesion of circulating cells to endothelial beds expressing E-selectin. 27888602 2 15 theme bone 264:267 arg1 BM-hMSCs 277:284 BM-hMSCs 277:284 BM-hMSCs 277:284 hMSCs derived from bone marrow (BM-hMSCs) natively lack endothelial binding capacity, but express a CD44 glycovariant containing N-linked sialyllactosamines that can be α(1,3)-fucosylated using fucosyltransferase-VI (FTVI) to enforce sLeX decorations, thereby creating hematopoietic cell E-/L-selectin ligand (HCELL). 27888602 2 15 theme bone 264:267 arg1 marrow 269:274 bone marrow 264:274 bone marrow (BM-hMSCs) 264:285 hMSCs derived from bone marrow (BM-hMSCs) natively lack endothelial binding capacity, but express a CD44 glycovariant containing N-linked sialyllactosamines that can be α(1,3)-fucosylated using fucosyltransferase-VI (FTVI) to enforce sLeX decorations, thereby creating hematopoietic cell E-/L-selectin ligand (HCELL). 27888602 9 16 theme -fucosylation 1999:2011 arg1 applicability 1963:1975 the applicability 1959:1975 the applicability of cell surface α(1,3)-fucosylation in programming migration of systemically administered A-hMSCs to sites of tissue injury/inflammation 1959:2112 Collectively, these data indicate that assembly of a sialyllactosaminyl-decorated CD44s glycovariant is a conserved feature of hMSCs derived from adipose tissue and marrow, thus identifying a CD44 glycosignature of these cells and supporting the applicability of cell surface α(1,3)-fucosylation in programming migration of systemically administered A-hMSCs to sites of tissue injury/inflammation. 27888602 6 17 theme standard 1286:1293 arg1 isoform 1309:1315 the "standard" CD44 (CD44s) isoform 1281:1315 the "standard" CD44 (CD44s) isoform 1281:1315 Moreover, treatment with the α(1,3)-fucosyltransferase-FTVII also generated expression of HCELL on both BM-hMSCs and A-hMSCs, with sLeX decorations created on N-linked glycans of the "standard" CD44 (CD44s) isoform. 27888602 1 18 theme administered 137:148 arg1 hMSCs 180:184 hMSCs 180:184 hMSCs 180:184 The clinical effectiveness of systemically administered human mesenchymal stem cells (hMSCs) depends on their capacity to engage vascular endothelium. 27888602 1 18 theme administered 137:148 arg1 cells 173:177 human mesenchymal stem cells 150:177 systemically administered human mesenchymal stem cells (hMSCs) 124:185 The clinical effectiveness of systemically administered human mesenchymal stem cells (hMSCs) depends on their capacity to engage vascular endothelium. 27888602 9 19 theme sialyllactosaminyl-decorated 1770:1797 arg1 glycovariant 1805:1816 a sialyllactosaminyl-decorated CD44s glycovariant 1768:1816 a sialyllactosaminyl-decorated CD44s glycovariant 1768:1816 Collectively, these data indicate that assembly of a sialyllactosaminyl-decorated CD44s glycovariant is a conserved feature of hMSCs derived from adipose tissue and marrow, thus identifying a CD44 glycosignature of these cells and supporting the applicability of cell surface α(1,3)-fucosylation in programming migration of systemically administered A-hMSCs to sites of tissue injury/inflammation. 27888602 9 20 theme programming 2016:2026 arg1 migration 2028:2036 programming migration 2016:2036 programming migration of systemically administered A-hMSCs to sites of tissue injury/inflammation 2016:2112 Collectively, these data indicate that assembly of a sialyllactosaminyl-decorated CD44s glycovariant is a conserved feature of hMSCs derived from adipose tissue and marrow, thus identifying a CD44 glycosignature of these cells and supporting the applicability of cell surface α(1,3)-fucosylation in programming migration of systemically administered A-hMSCs to sites of tissue injury/inflammation. 27888602 4 21 theme hMSCs 710:714 arg1 tissue 727:732 adipose tissue 719:732 adipose tissue (A-hMSCs) 719:742 An alternative source of hMSCs is adipose tissue (A-hMSCs), and we assessed whether A-hMSCs bind E-selectin and/or possess sialyllactosamine-decorated CD44 accessible to α(1,3)-fucosylation. 27888602 4 21 theme hMSCs 710:714 arg1 source 700:705 An alternative source 685:705 An alternative source of hMSCs 685:714 An alternative source of hMSCs is adipose tissue (A-hMSCs), and we assessed whether A-hMSCs bind E-selectin and/or possess sialyllactosamine-decorated CD44 accessible to α(1,3)-fucosylation. 27888602 3 22 theme circulating 624:634 arg1 cells 636:640 circulating cells 624:640 circulating cells 624:640 HCELL expression programs potent shear-resistant adhesion of circulating cells to endothelial beds expressing E-selectin. 27888602 1 23 theme mesenchymal 156:166 arg1 hMSCs 180:184 hMSCs 180:184 hMSCs 180:184 The clinical effectiveness of systemically administered human mesenchymal stem cells (hMSCs) depends on their capacity to engage vascular endothelium. 27888602 1 23 theme mesenchymal 156:166 arg1 cells 173:177 human mesenchymal stem cells 150:177 systemically administered human mesenchymal stem cells (hMSCs) 124:185 The clinical effectiveness of systemically administered human mesenchymal stem cells (hMSCs) depends on their capacity to engage vascular endothelium. 27888602 2 24 attach derived 251:257 arg1 BM-hMSCs 277:284 BM-hMSCs 277:284 BM-hMSCs 277:284 hMSCs derived from bone marrow (BM-hMSCs) natively lack endothelial binding capacity, but express a CD44 glycovariant containing N-linked sialyllactosamines that can be α(1,3)-fucosylated using fucosyltransferase-VI (FTVI) to enforce sLeX decorations, thereby creating hematopoietic cell E-/L-selectin ligand (HCELL). 27888602 2 24 attach derived 251:257 arg1 marrow 269:274 bone marrow 264:274 bone marrow (BM-hMSCs) 264:285 hMSCs derived from bone marrow (BM-hMSCs) natively lack endothelial binding capacity, but express a CD44 glycovariant containing N-linked sialyllactosamines that can be α(1,3)-fucosylated using fucosyltransferase-VI (FTVI) to enforce sLeX decorations, thereby creating hematopoietic cell E-/L-selectin ligand (HCELL). 27888602 2 24 attach derived 251:257 arg2 hMSCs 245:249 hMSCs 245:249 hMSCs derived from bone marrow (BM-hMSCs) 245:285 hMSCs derived from bone marrow (BM-hMSCs) natively lack endothelial binding capacity, but express a CD44 glycovariant containing N-linked sialyllactosamines that can be α(1,3)-fucosylated using fucosyltransferase-VI (FTVI) to enforce sLeX decorations, thereby creating hematopoietic cell E-/L-selectin ligand (HCELL). 27888602 2 25 theme sLeX 479:482 arg1 decorations 484:494 sLeX decorations 479:494 sLeX decorations 479:494 hMSCs derived from bone marrow (BM-hMSCs) natively lack endothelial binding capacity, but express a CD44 glycovariant containing N-linked sialyllactosamines that can be α(1,3)-fucosylated using fucosyltransferase-VI (FTVI) to enforce sLeX decorations, thereby creating hematopoietic cell E-/L-selectin ligand (HCELL). 27888602 4 26 theme adipose 719:725 arg1 A-hMSCs 735:741 A-hMSCs 735:741 A-hMSCs 735:741 An alternative source of hMSCs is adipose tissue (A-hMSCs), and we assessed whether A-hMSCs bind E-selectin and/or possess sialyllactosamine-decorated CD44 accessible to α(1,3)-fucosylation. 27888602 4 26 theme adipose 719:725 arg1 tissue 727:732 adipose tissue 719:732 adipose tissue (A-hMSCs) 719:742 An alternative source of hMSCs is adipose tissue (A-hMSCs), and we assessed whether A-hMSCs bind E-selectin and/or possess sialyllactosamine-decorated CD44 accessible to α(1,3)-fucosylation. 27888602 4 26 theme adipose 719:725 arg1 source 700:705 An alternative source 685:705 An alternative source of hMSCs 685:714 An alternative source of hMSCs is adipose tissue (A-hMSCs), and we assessed whether A-hMSCs bind E-selectin and/or possess sialyllactosamine-decorated CD44 accessible to α(1,3)-fucosylation. 27888602 0 27 theme Mesenchymal 70:80 arg1 Cells 87:91 Human Mesenchymal Stem Cells 64:91 Human Mesenchymal Stem Cells 64:91 A Glycovariant of Human CD44 is Characteristically Expressed on Human Mesenchymal Stem Cells. 27888602 1 28 theme cells 173:177 arg1 effectiveness 107:119 The clinical effectiveness 94:119 The clinical effectiveness of systemically administered human mesenchymal stem cells (hMSCs) 94:185 The clinical effectiveness of systemically administered human mesenchymal stem cells (hMSCs) depends on their capacity to engage vascular endothelium. 27888602 9 29 theme administered 2054:2065 arg1 A-hMSCs 2067:2073 systemically administered A-hMSCs 2041:2073 systemically administered A-hMSCs 2041:2073 Collectively, these data indicate that assembly of a sialyllactosaminyl-decorated CD44s glycovariant is a conserved feature of hMSCs derived from adipose tissue and marrow, thus identifying a CD44 glycosignature of these cells and supporting the applicability of cell surface α(1,3)-fucosylation in programming migration of systemically administered A-hMSCs to sites of tissue injury/inflammation. 27888602 1 30 theme clinical 98:105 arg1 effectiveness 107:119 The clinical effectiveness 94:119 The clinical effectiveness of systemically administered human mesenchymal stem cells (hMSCs) 94:185 The clinical effectiveness of systemically administered human mesenchymal stem cells (hMSCs) depends on their capacity to engage vascular endothelium. 27888602 5 31 theme α 984:984 arg1 -fucosylation 990:1002 FTVI-mediated cell surface α(1,3)-fucosylation 957:1002 FTVI-mediated cell surface α(1,3)-fucosylation 957:1002 Similar to BM-hMSCs, we found that A-hMSCs natively lack E-selectin ligands, but FTVI-mediated cell surface α(1,3)-fucosylation induces sLeX expression and robust E-selectin binding secondary to conversion of CD44 into HCELL. 27888602 5 32 theme 1,3 986:988 arg1 -fucosylation 990:1002 FTVI-mediated cell surface α(1,3)-fucosylation 957:1002 FTVI-mediated cell surface α(1,3)-fucosylation 957:1002 Similar to BM-hMSCs, we found that A-hMSCs natively lack E-selectin ligands, but FTVI-mediated cell surface α(1,3)-fucosylation induces sLeX expression and robust E-selectin binding secondary to conversion of CD44 into HCELL. 27888602 9 33 theme hMSCs 1844:1848 arg1 assembly 1756:1763 assembly 1756:1763 assembly of a sialyllactosaminyl-decorated CD44s glycovariant 1756:1816 Collectively, these data indicate that assembly of a sialyllactosaminyl-decorated CD44s glycovariant is a conserved feature of hMSCs derived from adipose tissue and marrow, thus identifying a CD44 glycosignature of these cells and supporting the applicability of cell surface α(1,3)-fucosylation in programming migration of systemically administered A-hMSCs to sites of tissue injury/inflammation. 27888602 9 33 theme hMSCs 1844:1848 arg1 feature 1833:1839 a conserved feature 1821:1839 a conserved feature of hMSCs derived from adipose tissue and marrow 1821:1887 Collectively, these data indicate that assembly of a sialyllactosaminyl-decorated CD44s glycovariant is a conserved feature of hMSCs derived from adipose tissue and marrow, thus identifying a CD44 glycosignature of these cells and supporting the applicability of cell surface α(1,3)-fucosylation in programming migration of systemically administered A-hMSCs to sites of tissue injury/inflammation. 27888602 9 34 theme conserved 1823:1831 arg1 assembly 1756:1763 assembly 1756:1763 assembly of a sialyllactosaminyl-decorated CD44s glycovariant 1756:1816 Collectively, these data indicate that assembly of a sialyllactosaminyl-decorated CD44s glycovariant is a conserved feature of hMSCs derived from adipose tissue and marrow, thus identifying a CD44 glycosignature of these cells and supporting the applicability of cell surface α(1,3)-fucosylation in programming migration of systemically administered A-hMSCs to sites of tissue injury/inflammation. 27888602 9 34 theme conserved 1823:1831 arg1 feature 1833:1839 a conserved feature 1821:1839 a conserved feature of hMSCs derived from adipose tissue and marrow 1821:1887 Collectively, these data indicate that assembly of a sialyllactosaminyl-decorated CD44s glycovariant is a conserved feature of hMSCs derived from adipose tissue and marrow, thus identifying a CD44 glycosignature of these cells and supporting the applicability of cell surface α(1,3)-fucosylation in programming migration of systemically administered A-hMSCs to sites of tissue injury/inflammation. 27888602 9 35 theme injury/inflammation 2094:2112 arg1 sites 2078:2082 sites 2078:2082 sites of tissue injury/inflammation 2078:2112 Collectively, these data indicate that assembly of a sialyllactosaminyl-decorated CD44s glycovariant is a conserved feature of hMSCs derived from adipose tissue and marrow, thus identifying a CD44 glycosignature of these cells and supporting the applicability of cell surface α(1,3)-fucosylation in programming migration of systemically administered A-hMSCs to sites of tissue injury/inflammation. 27888602 9 35 theme injury/inflammation 2094:2112 arg1 injury/inflammation 2094:2112 tissue injury/inflammation 2087:2112 tissue injury/inflammation 2087:2112 Collectively, these data indicate that assembly of a sialyllactosaminyl-decorated CD44s glycovariant is a conserved feature of hMSCs derived from adipose tissue and marrow, thus identifying a CD44 glycosignature of these cells and supporting the applicability of cell surface α(1,3)-fucosylation in programming migration of systemically administered A-hMSCs to sites of tissue injury/inflammation. 27888602 5 36 theme cell 971:974 arg1 -fucosylation 990:1002 FTVI-mediated cell surface α(1,3)-fucosylation 957:1002 FTVI-mediated cell surface α(1,3)-fucosylation 957:1002 Similar to BM-hMSCs, we found that A-hMSCs natively lack E-selectin ligands, but FTVI-mediated cell surface α(1,3)-fucosylation induces sLeX expression and robust E-selectin binding secondary to conversion of CD44 into HCELL. 27888602 8 37 theme hMSCs 1558:1562 arg1 types 1549:1553 both types 1544:1553 both types of hMSCs 1544:1562 These studies reveal that both types of hMSCs conspicuously lack transcripts encoding α(1,3)-fucosyltransferases, but equally express glycosyltransferases critical to creation of sialyllactosamines. 27888602 2 38 link N-linked 374:381 arg1 sialyllactosamines 383:400 N-linked sialyllactosamines 374:400 N-linked sialyllactosamines that can be α(1,3)-fucosylated using fucosyltransferase-VI (FTVI) to enforce sLeX decorations 374:494 hMSCs derived from bone marrow (BM-hMSCs) natively lack endothelial binding capacity, but express a CD44 glycovariant containing N-linked sialyllactosamines that can be α(1,3)-fucosylated using fucosyltransferase-VI (FTVI) to enforce sLeX decorations, thereby creating hematopoietic cell E-/L-selectin ligand (HCELL). 27888602 0 39 theme CD44 24:27 arg1 Glycovariant 2:13 A Glycovariant 0:13 A Glycovariant of Human CD44 0:27 A Glycovariant of Human CD44 is Characteristically Expressed on Human Mesenchymal Stem Cells. 27888602 9 40 attach derived 1850:1856 arg2 hMSCs 1844:1848 hMSCs 1844:1848 hMSCs derived from adipose tissue and marrow 1844:1887 Collectively, these data indicate that assembly of a sialyllactosaminyl-decorated CD44s glycovariant is a conserved feature of hMSCs derived from adipose tissue and marrow, thus identifying a CD44 glycosignature of these cells and supporting the applicability of cell surface α(1,3)-fucosylation in programming migration of systemically administered A-hMSCs to sites of tissue injury/inflammation. 27888602 9 40 attach derived 1850:1856 arg1 marrow 1882:1887 marrow 1882:1887 marrow 1882:1887 Collectively, these data indicate that assembly of a sialyllactosaminyl-decorated CD44s glycovariant is a conserved feature of hMSCs derived from adipose tissue and marrow, thus identifying a CD44 glycosignature of these cells and supporting the applicability of cell surface α(1,3)-fucosylation in programming migration of systemically administered A-hMSCs to sites of tissue injury/inflammation. 27888602 9 40 attach derived 1850:1856 arg1 tissue 1871:1876 adipose tissue 1863:1876 adipose tissue 1863:1876 Collectively, these data indicate that assembly of a sialyllactosaminyl-decorated CD44s glycovariant is a conserved feature of hMSCs derived from adipose tissue and marrow, thus identifying a CD44 glycosignature of these cells and supporting the applicability of cell surface α(1,3)-fucosylation in programming migration of systemically administered A-hMSCs to sites of tissue injury/inflammation. 27888602 5 41 theme E-selectin 1039:1048 arg1 binding 1050:1056 robust E-selectin binding 1032:1056 robust E-selectin binding 1032:1056 Similar to BM-hMSCs, we found that A-hMSCs natively lack E-selectin ligands, but FTVI-mediated cell surface α(1,3)-fucosylation induces sLeX expression and robust E-selectin binding secondary to conversion of CD44 into HCELL. 27888602 6 42 theme α 1131:1131 arg1 -fucosyltransferase-FTVII 1137:1161 the α(1,3)-fucosyltransferase-FTVII 1127:1161 the α(1,3)-fucosyltransferase-FTVII 1127:1161 Moreover, treatment with the α(1,3)-fucosyltransferase-FTVII also generated expression of HCELL on both BM-hMSCs and A-hMSCs, with sLeX decorations created on N-linked glycans of the "standard" CD44 (CD44s) isoform. 27888602 7 43 theme glycan 1500:1505 arg1 synthesis 1507:1515 lactosaminyl glycan synthesis 1487:1515 lactosaminyl glycan synthesis 1487:1515 The finding that hMSCs from both source tissues each lack native E-selectin ligand expression prompted examination of the expression of glycosyltransferases that direct lactosaminyl glycan synthesis. 27888602 10 44 theme Stem 2115:2118 arg1 Cells 2120:2124 Stem Cells 2115:2124 Stem Cells 2115:2124 Stem Cells 2017;35:1080-1092. 27888602 5 45 theme sLeX 1012:1015 arg1 expression 1017:1026 sLeX expression 1012:1026 sLeX expression 1012:1026 Similar to BM-hMSCs, we found that A-hMSCs natively lack E-selectin ligands, but FTVI-mediated cell surface α(1,3)-fucosylation induces sLeX expression and robust E-selectin binding secondary to conversion of CD44 into HCELL. 27888602 9 46 theme glycovariant 1805:1816 arg1 assembly 1756:1763 assembly 1756:1763 assembly of a sialyllactosaminyl-decorated CD44s glycovariant 1756:1816 Collectively, these data indicate that assembly of a sialyllactosaminyl-decorated CD44s glycovariant is a conserved feature of hMSCs derived from adipose tissue and marrow, thus identifying a CD44 glycosignature of these cells and supporting the applicability of cell surface α(1,3)-fucosylation in programming migration of systemically administered A-hMSCs to sites of tissue injury/inflammation. 27888602 9 46 theme glycovariant 1805:1816 arg1 feature 1833:1839 a conserved feature 1821:1839 a conserved feature of hMSCs derived from adipose tissue and marrow 1821:1887 Collectively, these data indicate that assembly of a sialyllactosaminyl-decorated CD44s glycovariant is a conserved feature of hMSCs derived from adipose tissue and marrow, thus identifying a CD44 glycosignature of these cells and supporting the applicability of cell surface α(1,3)-fucosylation in programming migration of systemically administered A-hMSCs to sites of tissue injury/inflammation. 27888602 2 47 theme CD44 345:348 arg1 glycovariant 350:361 a CD44 glycovariant 343:361 a CD44 glycovariant containing N-linked sialyllactosamines that can be α(1,3)-fucosylated using fucosyltransferase-VI (FTVI) to enforce sLeX decorations 343:494 hMSCs derived from bone marrow (BM-hMSCs) natively lack endothelial binding capacity, but express a CD44 glycovariant containing N-linked sialyllactosamines that can be α(1,3)-fucosylated using fucosyltransferase-VI (FTVI) to enforce sLeX decorations, thereby creating hematopoietic cell E-/L-selectin ligand (HCELL). 27888602 7 48 theme glycosyltransferases 1454:1473 arg1 expression 1440:1449 the expression 1436:1449 the expression of glycosyltransferases that direct lactosaminyl glycan synthesis 1436:1515 The finding that hMSCs from both source tissues each lack native E-selectin ligand expression prompted examination of the expression of glycosyltransferases that direct lactosaminyl glycan synthesis. 27888602 10 49 dep 35:1080-1092 2131:2142 arg1 Cells 2120:2124 Stem Cells 2115:2124 Stem Cells 2115:2124 Stem Cells 2017;35:1080-1092. 27888602 3 50 theme HCELL 563:567 arg1 expression 569:578 HCELL expression 563:578 HCELL expression 563:578 HCELL expression programs potent shear-resistant adhesion of circulating cells to endothelial beds expressing E-selectin. 27888602 7 51 theme expression 1440:1449 arg1 examination 1421:1431 examination 1421:1431 examination of the expression of glycosyltransferases that direct lactosaminyl glycan synthesis 1421:1515 The finding that hMSCs from both source tissues each lack native E-selectin ligand expression prompted examination of the expression of glycosyltransferases that direct lactosaminyl glycan synthesis. 27888602 6 52 theme N-linked 1261:1268 arg1 glycans 1270:1276 N-linked glycans 1261:1276 N-linked glycans of the "standard" CD44 (CD44s) isoform 1261:1315 Moreover, treatment with the α(1,3)-fucosyltransferase-FTVII also generated expression of HCELL on both BM-hMSCs and A-hMSCs, with sLeX decorations created on N-linked glycans of the "standard" CD44 (CD44s) isoform. 27888602 6 53 with treatment 1112:1120 arg1 -fucosyltransferase-FTVII 1137:1161 the α(1,3)-fucosyltransferase-FTVII 1127:1161 the α(1,3)-fucosyltransferase-FTVII 1127:1161 Moreover, treatment with the α(1,3)-fucosyltransferase-FTVII also generated expression of HCELL on both BM-hMSCs and A-hMSCs, with sLeX decorations created on N-linked glycans of the "standard" CD44 (CD44s) isoform. 27888602 4 54 theme 1,3 857:859 arg1 -fucosylation 861:873 α(1,3)-fucosylation 855:873 α(1,3)-fucosylation 855:873 An alternative source of hMSCs is adipose tissue (A-hMSCs), and we assessed whether A-hMSCs bind E-selectin and/or possess sialyllactosamine-decorated CD44 accessible to α(1,3)-fucosylation. 27888602 2 55 theme binding 313:319 arg1 capacity 321:328 endothelial binding capacity 301:328 endothelial binding capacity 301:328 hMSCs derived from bone marrow (BM-hMSCs) natively lack endothelial binding capacity, but express a CD44 glycovariant containing N-linked sialyllactosamines that can be α(1,3)-fucosylated using fucosyltransferase-VI (FTVI) to enforce sLeX decorations, thereby creating hematopoietic cell E-/L-selectin ligand (HCELL). 27888602 7 56 theme E-selectin 1383:1392 arg1 ligand 1394:1399 native E-selectin ligand 1376:1399 native E-selectin ligand expression 1376:1410 The finding that hMSCs from both source tissues each lack native E-selectin ligand expression prompted examination of the expression of glycosyltransferases that direct lactosaminyl glycan synthesis. 27888602 4 57 theme alternative 688:698 arg1 tissue 727:732 adipose tissue 719:732 adipose tissue (A-hMSCs) 719:742 An alternative source of hMSCs is adipose tissue (A-hMSCs), and we assessed whether A-hMSCs bind E-selectin and/or possess sialyllactosamine-decorated CD44 accessible to α(1,3)-fucosylation. 27888602 4 57 theme alternative 688:698 arg1 source 700:705 An alternative source 685:705 An alternative source of hMSCs 685:714 An alternative source of hMSCs is adipose tissue (A-hMSCs), and we assessed whether A-hMSCs bind E-selectin and/or possess sialyllactosamine-decorated CD44 accessible to α(1,3)-fucosylation. 27888602 6 58 theme 1,3 1133:1135 arg1 -fucosyltransferase-FTVII 1137:1161 the α(1,3)-fucosyltransferase-FTVII 1127:1161 the α(1,3)-fucosyltransferase-FTVII 1127:1161 Moreover, treatment with the α(1,3)-fucosyltransferase-FTVII also generated expression of HCELL on both BM-hMSCs and A-hMSCs, with sLeX decorations created on N-linked glycans of the "standard" CD44 (CD44s) isoform. 27888602 9 59 theme surface 1985:1991 arg1 -fucosylation 1999:2011 cell surface α(1,3)-fucosylation 1980:2011 cell surface α(1,3)-fucosylation 1980:2011 Collectively, these data indicate that assembly of a sialyllactosaminyl-decorated CD44s glycovariant is a conserved feature of hMSCs derived from adipose tissue and marrow, thus identifying a CD44 glycosignature of these cells and supporting the applicability of cell surface α(1,3)-fucosylation in programming migration of systemically administered A-hMSCs to sites of tissue injury/inflammation. 27888602 5 60 theme CD44 1085:1088 arg1 conversion 1071:1080 conversion 1071:1080 conversion of CD44 into HCELL 1071:1099 Similar to BM-hMSCs, we found that A-hMSCs natively lack E-selectin ligands, but FTVI-mediated cell surface α(1,3)-fucosylation induces sLeX expression and robust E-selectin binding secondary to conversion of CD44 into HCELL. 27888602 3 61 theme shear-resistant 596:610 arg1 adhesion 612:619 potent shear-resistant adhesion 589:619 potent shear-resistant adhesion of circulating cells to endothelial beds expressing E-selectin 589:682 HCELL expression programs potent shear-resistant adhesion of circulating cells to endothelial beds expressing E-selectin. 27888602 2 62 theme E-/L-selectin 533:545 arg1 HCELL 555:559 HCELL 555:559 HCELL 555:559 hMSCs derived from bone marrow (BM-hMSCs) natively lack endothelial binding capacity, but express a CD44 glycovariant containing N-linked sialyllactosamines that can be α(1,3)-fucosylated using fucosyltransferase-VI (FTVI) to enforce sLeX decorations, thereby creating hematopoietic cell E-/L-selectin ligand (HCELL). 27888602 2 62 theme E-/L-selectin 533:545 arg1 ligand 547:552 E-/L-selectin ligand 533:552 hematopoietic cell E-/L-selectin ligand (HCELL) 514:560 hMSCs derived from bone marrow (BM-hMSCs) natively lack endothelial binding capacity, but express a CD44 glycovariant containing N-linked sialyllactosamines that can be α(1,3)-fucosylated using fucosyltransferase-VI (FTVI) to enforce sLeX decorations, thereby creating hematopoietic cell E-/L-selectin ligand (HCELL). 27888602 9 63 dep feature 1833:1839 arg1 supporting 1948:1957 supporting 1948:1957 supporting the applicability of cell surface α(1,3)-fucosylation in programming migration of systemically administered A-hMSCs to sites of tissue injury/inflammation 1948:2112 Collectively, these data indicate that assembly of a sialyllactosaminyl-decorated CD44s glycovariant is a conserved feature of hMSCs derived from adipose tissue and marrow, thus identifying a CD44 glycosignature of these cells and supporting the applicability of cell surface α(1,3)-fucosylation in programming migration of systemically administered A-hMSCs to sites of tissue injury/inflammation. 27888602 9 63 dep feature 1833:1839 arg1 identifying 1895:1905 identifying 1895:1905 identifying a CD44 glycosignature of these cells 1895:1942 Collectively, these data indicate that assembly of a sialyllactosaminyl-decorated CD44s glycovariant is a conserved feature of hMSCs derived from adipose tissue and marrow, thus identifying a CD44 glycosignature of these cells and supporting the applicability of cell surface α(1,3)-fucosylation in programming migration of systemically administered A-hMSCs to sites of tissue injury/inflammation. 27888602 6 64 theme " 1294:1294 arg1 isoform 1309:1315 the "standard" CD44 (CD44s) isoform 1281:1315 the "standard" CD44 (CD44s) isoform 1281:1315 Moreover, treatment with the α(1,3)-fucosyltransferase-FTVII also generated expression of HCELL on both BM-hMSCs and A-hMSCs, with sLeX decorations created on N-linked glycans of the "standard" CD44 (CD44s) isoform. 27888602 5 65 theme secondary 1058:1066 arg1 expression 1017:1026 sLeX expression 1012:1026 sLeX expression 1012:1026 Similar to BM-hMSCs, we found that A-hMSCs natively lack E-selectin ligands, but FTVI-mediated cell surface α(1,3)-fucosylation induces sLeX expression and robust E-selectin binding secondary to conversion of CD44 into HCELL. 27888602 3 66 theme cells 636:640 arg1 adhesion 612:619 potent shear-resistant adhesion 589:619 potent shear-resistant adhesion of circulating cells to endothelial beds expressing E-selectin 589:682 HCELL expression programs potent shear-resistant adhesion of circulating cells to endothelial beds expressing E-selectin. 27888602 5 67 theme E-selectin 933:942 arg1 ligands 944:950 E-selectin ligands 933:950 E-selectin ligands 933:950 Similar to BM-hMSCs, we found that A-hMSCs natively lack E-selectin ligands, but FTVI-mediated cell surface α(1,3)-fucosylation induces sLeX expression and robust E-selectin binding secondary to conversion of CD44 into HCELL. 27888602 9 68 from applicability 1963:1975 arg1 migration 2028:2036 programming migration 2016:2036 programming migration of systemically administered A-hMSCs to sites of tissue injury/inflammation 2016:2112 Collectively, these data indicate that assembly of a sialyllactosaminyl-decorated CD44s glycovariant is a conserved feature of hMSCs derived from adipose tissue and marrow, thus identifying a CD44 glycosignature of these cells and supporting the applicability of cell surface α(1,3)-fucosylation in programming migration of systemically administered A-hMSCs to sites of tissue injury/inflammation. 27888602 0 69 theme Human 64:68 arg1 Cells 87:91 Human Mesenchymal Stem Cells 64:91 Human Mesenchymal Stem Cells 64:91 A Glycovariant of Human CD44 is Characteristically Expressed on Human Mesenchymal Stem Cells. 27888602 1 70 theme human 150:154 arg1 hMSCs 180:184 hMSCs 180:184 hMSCs 180:184 The clinical effectiveness of systemically administered human mesenchymal stem cells (hMSCs) depends on their capacity to engage vascular endothelium. 27888602 1 70 theme human 150:154 arg1 cells 173:177 human mesenchymal stem cells 150:177 systemically administered human mesenchymal stem cells (hMSCs) 124:185 The clinical effectiveness of systemically administered human mesenchymal stem cells (hMSCs) depends on their capacity to engage vascular endothelium. 27888602 9 71 theme CD44s 1799:1803 arg1 glycovariant 1805:1816 a sialyllactosaminyl-decorated CD44s glycovariant 1768:1816 a sialyllactosaminyl-decorated CD44s glycovariant 1768:1816 Collectively, these data indicate that assembly of a sialyllactosaminyl-decorated CD44s glycovariant is a conserved feature of hMSCs derived from adipose tissue and marrow, thus identifying a CD44 glycosignature of these cells and supporting the applicability of cell surface α(1,3)-fucosylation in programming migration of systemically administered A-hMSCs to sites of tissue injury/inflammation. 27888602 4 72 contain possess 800:806 arg1 A-hMSCs 769:775 A-hMSCs 769:775 A-hMSCs 769:775 An alternative source of hMSCs is adipose tissue (A-hMSCs), and we assessed whether A-hMSCs bind E-selectin and/or possess sialyllactosamine-decorated CD44 accessible to α(1,3)-fucosylation. 27888602 4 72 contain possess 800:806 arg2 CD44 836:839 sialyllactosamine-decorated CD44 808:839 sialyllactosamine-decorated CD44 accessible to α(1,3)-fucosylation 808:873 An alternative source of hMSCs is adipose tissue (A-hMSCs), and we assessed whether A-hMSCs bind E-selectin and/or possess sialyllactosamine-decorated CD44 accessible to α(1,3)-fucosylation. 27888602 0 73 theme Stem 82:85 arg1 Cells 87:91 Human Mesenchymal Stem Cells 64:91 Human Mesenchymal Stem Cells 64:91 A Glycovariant of Human CD44 is Characteristically Expressed on Human Mesenchymal Stem Cells. 27888602 1 74 theme stem 168:171 arg1 hMSCs 180:184 hMSCs 180:184 hMSCs 180:184 The clinical effectiveness of systemically administered human mesenchymal stem cells (hMSCs) depends on their capacity to engage vascular endothelium. 27888602 1 74 theme stem 168:171 arg1 cells 173:177 human mesenchymal stem cells 150:177 systemically administered human mesenchymal stem cells (hMSCs) 124:185 The clinical effectiveness of systemically administered human mesenchymal stem cells (hMSCs) depends on their capacity to engage vascular endothelium. 27888602 5 75 theme surface 976:982 arg1 -fucosylation 990:1002 FTVI-mediated cell surface α(1,3)-fucosylation 957:1002 FTVI-mediated cell surface α(1,3)-fucosylation 957:1002 Similar to BM-hMSCs, we found that A-hMSCs natively lack E-selectin ligands, but FTVI-mediated cell surface α(1,3)-fucosylation induces sLeX expression and robust E-selectin binding secondary to conversion of CD44 into HCELL. 27888602 2 76 theme hematopoietic 514:526 arg1 cell 528:531 hematopoietic cell E-/L-selectin ligand (HCELL) 514:560 hematopoietic cell E-/L-selectin ligand (HCELL) 514:560 hMSCs derived from bone marrow (BM-hMSCs) natively lack endothelial binding capacity, but express a CD44 glycovariant containing N-linked sialyllactosamines that can be α(1,3)-fucosylated using fucosyltransferase-VI (FTVI) to enforce sLeX decorations, thereby creating hematopoietic cell E-/L-selectin ligand (HCELL). 27888602 9 77 theme A-hMSCs 2067:2073 arg1 migration 2028:2036 programming migration 2016:2036 programming migration of systemically administered A-hMSCs to sites of tissue injury/inflammation 2016:2112 Collectively, these data indicate that assembly of a sialyllactosaminyl-decorated CD44s glycovariant is a conserved feature of hMSCs derived from adipose tissue and marrow, thus identifying a CD44 glycosignature of these cells and supporting the applicability of cell surface α(1,3)-fucosylation in programming migration of systemically administered A-hMSCs to sites of tissue injury/inflammation. 27888602 6 78 link N-linked 1261:1268 arg1 glycans 1270:1276 N-linked glycans 1261:1276 N-linked glycans of the "standard" CD44 (CD44s) isoform 1261:1315 Moreover, treatment with the α(1,3)-fucosyltransferase-FTVII also generated expression of HCELL on both BM-hMSCs and A-hMSCs, with sLeX decorations created on N-linked glycans of the "standard" CD44 (CD44s) isoform. 27888602 6 79 from expression 1178:1187 arg1 BM-hMSCs 1206:1213 BM-hMSCs 1206:1213 BM-hMSCs 1206:1213 Moreover, treatment with the α(1,3)-fucosyltransferase-FTVII also generated expression of HCELL on both BM-hMSCs and A-hMSCs, with sLeX decorations created on N-linked glycans of the "standard" CD44 (CD44s) isoform. 27888602 6 79 from expression 1178:1187 arg1 A-hMSCs 1219:1225 A-hMSCs 1219:1225 A-hMSCs 1219:1225 Moreover, treatment with the α(1,3)-fucosyltransferase-FTVII also generated expression of HCELL on both BM-hMSCs and A-hMSCs, with sLeX decorations created on N-linked glycans of the "standard" CD44 (CD44s) isoform. 27888602 2 80 contain containing 363:372 arg1 glycovariant 350:361 a CD44 glycovariant 343:361 a CD44 glycovariant containing N-linked sialyllactosamines that can be α(1,3)-fucosylated using fucosyltransferase-VI (FTVI) to enforce sLeX decorations 343:494 hMSCs derived from bone marrow (BM-hMSCs) natively lack endothelial binding capacity, but express a CD44 glycovariant containing N-linked sialyllactosamines that can be α(1,3)-fucosylated using fucosyltransferase-VI (FTVI) to enforce sLeX decorations, thereby creating hematopoietic cell E-/L-selectin ligand (HCELL). 27888602 2 80 contain containing 363:372 arg2 sialyllactosamines 383:400 N-linked sialyllactosamines 374:400 N-linked sialyllactosamines that can be α(1,3)-fucosylated using fucosyltransferase-VI (FTVI) to enforce sLeX decorations 374:494 hMSCs derived from bone marrow (BM-hMSCs) natively lack endothelial binding capacity, but express a CD44 glycovariant containing N-linked sialyllactosamines that can be α(1,3)-fucosylated using fucosyltransferase-VI (FTVI) to enforce sLeX decorations, thereby creating hematopoietic cell E-/L-selectin ligand (HCELL). 27888602 9 81 theme tissue 2087:2092 arg1 injury/inflammation 2094:2112 tissue injury/inflammation 2087:2112 tissue injury/inflammation 2087:2112 Collectively, these data indicate that assembly of a sialyllactosaminyl-decorated CD44s glycovariant is a conserved feature of hMSCs derived from adipose tissue and marrow, thus identifying a CD44 glycosignature of these cells and supporting the applicability of cell surface α(1,3)-fucosylation in programming migration of systemically administered A-hMSCs to sites of tissue injury/inflammation. 27888602 2 82 theme N-linked 374:381 arg1 sialyllactosamines 383:400 N-linked sialyllactosamines 374:400 N-linked sialyllactosamines that can be α(1,3)-fucosylated using fucosyltransferase-VI (FTVI) to enforce sLeX decorations 374:494 hMSCs derived from bone marrow (BM-hMSCs) natively lack endothelial binding capacity, but express a CD44 glycovariant containing N-linked sialyllactosamines that can be α(1,3)-fucosylated using fucosyltransferase-VI (FTVI) to enforce sLeX decorations, thereby creating hematopoietic cell E-/L-selectin ligand (HCELL). 27888602 0 83 theme Human 18:22 arg1 CD44 24:27 Human CD44 18:27 Human CD44 18:27 A Glycovariant of Human CD44 is Characteristically Expressed on Human Mesenchymal Stem Cells. 27888602 5 84 theme FTVI-mediated 957:969 arg1 -fucosylation 990:1002 FTVI-mediated cell surface α(1,3)-fucosylation 957:1002 FTVI-mediated cell surface α(1,3)-fucosylation 957:1002 Similar to BM-hMSCs, we found that A-hMSCs natively lack E-selectin ligands, but FTVI-mediated cell surface α(1,3)-fucosylation induces sLeX expression and robust E-selectin binding secondary to conversion of CD44 into HCELL. 27888602 6 85 theme sLeX 1233:1236 arg1 decorations 1238:1248 sLeX decorations 1233:1248 sLeX decorations created on N-linked glycans of the "standard" CD44 (CD44s) isoform 1233:1315 Moreover, treatment with the α(1,3)-fucosyltransferase-FTVII also generated expression of HCELL on both BM-hMSCs and A-hMSCs, with sLeX decorations created on N-linked glycans of the "standard" CD44 (CD44s) isoform. 27888602 9 86 theme adipose 1863:1869 arg1 tissue 1871:1876 adipose tissue 1863:1876 adipose tissue 1863:1876 Collectively, these data indicate that assembly of a sialyllactosaminyl-decorated CD44s glycovariant is a conserved feature of hMSCs derived from adipose tissue and marrow, thus identifying a CD44 glycosignature of these cells and supporting the applicability of cell surface α(1,3)-fucosylation in programming migration of systemically administered A-hMSCs to sites of tissue injury/inflammation. 27888602 2 87 dep cell 528:531 arg1 HCELL 555:559 HCELL 555:559 HCELL 555:559 hMSCs derived from bone marrow (BM-hMSCs) natively lack endothelial binding capacity, but express a CD44 glycovariant containing N-linked sialyllactosamines that can be α(1,3)-fucosylated using fucosyltransferase-VI (FTVI) to enforce sLeX decorations, thereby creating hematopoietic cell E-/L-selectin ligand (HCELL). 27888602 2 87 dep cell 528:531 arg1 ligand 547:552 E-/L-selectin ligand 533:552 hematopoietic cell E-/L-selectin ligand (HCELL) 514:560 hMSCs derived from bone marrow (BM-hMSCs) natively lack endothelial binding capacity, but express a CD44 glycovariant containing N-linked sialyllactosamines that can be α(1,3)-fucosylated using fucosyltransferase-VI (FTVI) to enforce sLeX decorations, thereby creating hematopoietic cell E-/L-selectin ligand (HCELL). 27888602 7 88 from tissues 1358:1364 arg1 hMSCs 1335:1339 hMSCs 1335:1339 hMSCs from both source tissues each lack native E-selectin ligand expression 1335:1410 The finding that hMSCs from both source tissues each lack native E-selectin ligand expression prompted examination of the expression of glycosyltransferases that direct lactosaminyl glycan synthesis. 27888602 3 89 theme endothelial 645:655 arg1 beds 657:660 endothelial beds 645:660 endothelial beds expressing E-selectin 645:682 HCELL expression programs potent shear-resistant adhesion of circulating cells to endothelial beds expressing E-selectin. 27888602 4 90 theme accessible 841:850 arg1 CD44 836:839 sialyllactosamine-decorated CD44 808:839 sialyllactosamine-decorated CD44 accessible to α(1,3)-fucosylation 808:873 An alternative source of hMSCs is adipose tissue (A-hMSCs), and we assessed whether A-hMSCs bind E-selectin and/or possess sialyllactosamine-decorated CD44 accessible to α(1,3)-fucosylation. 27888602 5 91 theme robust 1032:1037 arg1 binding 1050:1056 robust E-selectin binding 1032:1056 robust E-selectin binding 1032:1056 Similar to BM-hMSCs, we found that A-hMSCs natively lack E-selectin ligands, but FTVI-mediated cell surface α(1,3)-fucosylation induces sLeX expression and robust E-selectin binding secondary to conversion of CD44 into HCELL. 27888602 4 92 theme α 855:855 arg1 -fucosylation 861:873 α(1,3)-fucosylation 855:873 α(1,3)-fucosylation 855:873 An alternative source of hMSCs is adipose tissue (A-hMSCs), and we assessed whether A-hMSCs bind E-selectin and/or possess sialyllactosamine-decorated CD44 accessible to α(1,3)-fucosylation. 27888602 8 93 theme critical 1673:1680 arg1 glycosyltransferases 1652:1671 glycosyltransferases 1652:1671 glycosyltransferases critical to creation of sialyllactosamines 1652:1714 These studies reveal that both types of hMSCs conspicuously lack transcripts encoding α(1,3)-fucosyltransferases, but equally express glycosyltransferases critical to creation of sialyllactosamines. 27888602 2 94 gly -fucosylated 420:431 arg1 sialyllactosamines 383:400 N-linked sialyllactosamines 374:400 N-linked sialyllactosamines that can be α(1,3)-fucosylated using fucosyltransferase-VI (FTVI) to enforce sLeX decorations 374:494 hMSCs derived from bone marrow (BM-hMSCs) natively lack endothelial binding capacity, but express a CD44 glycovariant containing N-linked sialyllactosamines that can be α(1,3)-fucosylated using fucosyltransferase-VI (FTVI) to enforce sLeX decorations, thereby creating hematopoietic cell E-/L-selectin ligand (HCELL). 27888602 1 95 theme vascular 223:230 arg1 endothelium 232:242 vascular endothelium 223:242 vascular endothelium 223:242 The clinical effectiveness of systemically administered human mesenchymal stem cells (hMSCs) depends on their capacity to engage vascular endothelium. 27888602 9 96 theme CD44 1909:1912 arg1 glycosignature 1914:1927 a CD44 glycosignature 1907:1927 a CD44 glycosignature of these cells 1907:1942 Collectively, these data indicate that assembly of a sialyllactosaminyl-decorated CD44s glycovariant is a conserved feature of hMSCs derived from adipose tissue and marrow, thus identifying a CD44 glycosignature of these cells and supporting the applicability of cell surface α(1,3)-fucosylation in programming migration of systemically administered A-hMSCs to sites of tissue injury/inflammation. 27888602 4 97 theme sialyllactosamine-decorated 808:834 arg1 CD44 836:839 sialyllactosamine-decorated CD44 808:839 sialyllactosamine-decorated CD44 accessible to α(1,3)-fucosylation 808:873 An alternative source of hMSCs is adipose tissue (A-hMSCs), and we assessed whether A-hMSCs bind E-selectin and/or possess sialyllactosamine-decorated CD44 accessible to α(1,3)-fucosylation. 27888602 8 98 theme sialyllactosamines 1697:1714 arg1 creation 1685:1692 creation 1685:1692 creation of sialyllactosamines 1685:1714 These studies reveal that both types of hMSCs conspicuously lack transcripts encoding α(1,3)-fucosyltransferases, but equally express glycosyltransferases critical to creation of sialyllactosamines. 28596490 7 0 theme common 1197:1202 arg1 polymorphism 1222:1233 a relatively common single nucleotide polymorphism 1184:1233 a relatively common single nucleotide polymorphism 1184:1233 Surveying a small set of CAFs from breast cancer biopsies, we found that a relatively common single nucleotide polymorphism, which results in the expression of a GPER variant with the amino acid substitution P16L, is associated with the nuclear localization of GPER. 28596490 7 1 theme small 1123:1127 arg1 CAFs 1136:1139 CAFs 1136:1139 CAFs from breast cancer biopsies 1136:1167 Surveying a small set of CAFs from breast cancer biopsies, we found that a relatively common single nucleotide polymorphism, which results in the expression of a GPER variant with the amino acid substitution P16L, is associated with the nuclear localization of GPER. 28596490 7 1 theme small 1123:1127 arg1 set 1129:1131 a small set 1121:1131 a small set of CAFs from breast cancer biopsies 1121:1167 Surveying a small set of CAFs from breast cancer biopsies, we found that a relatively common single nucleotide polymorphism, which results in the expression of a GPER variant with the amino acid substitution P16L, is associated with the nuclear localization of GPER. 28596490 7 2 theme single 1204:1209 arg1 polymorphism 1222:1233 a relatively common single nucleotide polymorphism 1184:1233 a relatively common single nucleotide polymorphism 1184:1233 Surveying a small set of CAFs from breast cancer biopsies, we found that a relatively common single nucleotide polymorphism, which results in the expression of a GPER variant with the amino acid substitution P16L, is associated with the nuclear localization of GPER. 28596490 8 3 theme glycosylation 1479:1491 arg1 sites 1493:1497 the nearby glycosylation sites 1468:1497 the nearby glycosylation sites 1468:1497 GPER with P16L fails to be glycosylated, presumably because of a conformational effect on the nearby glycosylation sites. 28596490 0 4 theme carcinoma 199:207 arg1 cells 209:213 breast carcinoma cells 192:213 breast carcinoma cells 192:213 A genetic polymorphism repurposes the G-protein coupled and membrane-associated estrogen receptor GPER to a transcription factor-like molecule promoting paracrine signaling between stroma and breast carcinoma cells. 28596490 5 5 theme functional 890:899 arg1 significance 901:912 its functional significance 886:912 its functional significance 886:912 We decided to find out what induces the nuclear localization of GPER, how general this phenomenon is, and what its functional significance is. 28596490 1 6 theme G-protein 281:289 arg1 receptors 299:307 G-protein coupled receptors 281:307 G-protein coupled receptors 281:307 GPER is a membrane-associated estrogen receptor of the family of G-protein coupled receptors. 28596490 8 7 from effect 1458:1463 arg1 sites 1493:1497 the nearby glycosylation sites 1468:1497 the nearby glycosylation sites 1468:1497 GPER with P16L fails to be glycosylated, presumably because of a conformational effect on the nearby glycosylation sites. 28596490 8 8 theme nearby 1472:1477 arg1 sites 1493:1497 the nearby glycosylation sites 1468:1497 the nearby glycosylation sites 1468:1497 GPER with P16L fails to be glycosylated, presumably because of a conformational effect on the nearby glycosylation sites. 28596490 1 9 theme coupled 291:297 arg1 receptors 299:307 G-protein coupled receptors 281:307 G-protein coupled receptors 281:307 GPER is a membrane-associated estrogen receptor of the family of G-protein coupled receptors. 28596490 2 10 theme breast 314:319 arg1 cancer 321:326 breast cancer 314:326 breast cancer 314:326 For breast cancer, the contribution of GPER to promoting the proliferation and migration of both carcinoma cells and cancer-associated fibroblasts (CAFs) in response to estrogen and other agonists has extensively been investigated. 28596490 2 11 dep proliferation 371:383 arg1 the 367:369 the 367:369 the 367:369 For breast cancer, the contribution of GPER to promoting the proliferation and migration of both carcinoma cells and cancer-associated fibroblasts (CAFs) in response to estrogen and other agonists has extensively been investigated. 28596490 1 12 theme receptors 299:307 arg1 family 271:276 the family 267:276 the family of G-protein coupled receptors 267:307 GPER is a membrane-associated estrogen receptor of the family of G-protein coupled receptors. 28596490 0 13 theme factor-like 122:132 arg1 molecule 134:141 a transcription factor-like molecule 106:141 a transcription factor-like molecule promoting paracrine signaling between stroma and breast carcinoma cells 106:213 A genetic polymorphism repurposes the G-protein coupled and membrane-associated estrogen receptor GPER to a transcription factor-like molecule promoting paracrine signaling between stroma and breast carcinoma cells. 28596490 4 14 theme nuclear 659:665 arg1 GPER 667:670 this nuclear GPER 654:670 this nuclear GPER 654:670 Moreover, this nuclear GPER was shown to bind regulatory sequences of cancer-relevant target genes and to induce their expression. 28596490 7 15 theme amino 1295:1299 arg1 substitution 1306:1317 the amino acid substitution P16L 1291:1322 the amino acid substitution P16L 1291:1322 Surveying a small set of CAFs from breast cancer biopsies, we found that a relatively common single nucleotide polymorphism, which results in the expression of a GPER variant with the amino acid substitution P16L, is associated with the nuclear localization of GPER. 28596490 8 16 gly glycosylated 1405:1416 arg1 GPER 1378:1381 GPER 1378:1381 GPER with P16L 1378:1391 GPER with P16L fails to be glycosylated, presumably because of a conformational effect on the nearby glycosylation sites. 28596490 0 17 theme transcription 108:120 arg1 molecule 134:141 a transcription factor-like molecule 106:141 a transcription factor-like molecule promoting paracrine signaling between stroma and breast carcinoma cells 106:213 A genetic polymorphism repurposes the G-protein coupled and membrane-associated estrogen receptor GPER to a transcription factor-like molecule promoting paracrine signaling between stroma and breast carcinoma cells. 28596490 8 18 gly glycosylation 1479:1491 arg2 sites 1493:1497 the nearby glycosylation sites 1468:1497 the nearby glycosylation sites 1468:1497 GPER with P16L fails to be glycosylated, presumably because of a conformational effect on the nearby glycosylation sites. 28596490 5 19 dep induces 803:809 arg1 is 873:874 is 873:874 is 873:874 We decided to find out what induces the nuclear localization of GPER, how general this phenomenon is, and what its functional significance is. 28596490 9 20 theme membrane-associated 1527:1545 arg1 signaling 1547:1555 membrane-associated signaling 1527:1555 membrane-associated signaling 1527:1555 GPER P16L is defective for membrane-associated signaling, but instead acts like an estrogen-stimulated transcription factor. 28596490 3 21 located localized 588:596 arg2 GPER 556:559 GPER 556:559 GPER 556:559 Intriguingly, GPER was previously found to be localized to the nucleus in one isolate of breast CAFs. 28596490 3 21 located localized 588:596 arg1 isolate 620:626 one isolate 616:626 one isolate of breast CAFs 616:641 Intriguingly, GPER was previously found to be localized to the nucleus in one isolate of breast CAFs. 28596490 2 22 theme cells 417:421 arg1 migration 389:397 migration 389:397 migration 389:397 For breast cancer, the contribution of GPER to promoting the proliferation and migration of both carcinoma cells and cancer-associated fibroblasts (CAFs) in response to estrogen and other agonists has extensively been investigated. 28596490 2 22 theme cells 417:421 arg1 proliferation 371:383 proliferation 371:383 proliferation 371:383 For breast cancer, the contribution of GPER to promoting the proliferation and migration of both carcinoma cells and cancer-associated fibroblasts (CAFs) in response to estrogen and other agonists has extensively been investigated. 28596490 0 23 theme genetic 2:8 arg1 polymorphism 10:21 A genetic polymorphism 0:21 A genetic polymorphism 0:21 A genetic polymorphism repurposes the G-protein coupled and membrane-associated estrogen receptor GPER to a transcription factor-like molecule promoting paracrine signaling between stroma and breast carcinoma cells. 28596490 5 24 dep find 789:792 arg1 is 914:915 is 914:915 is 914:915 We decided to find out what induces the nuclear localization of GPER, how general this phenomenon is, and what its functional significance is. 28596490 5 24 dep find 789:792 arg1 induces 803:809 induces 803:809 induces 803:809 We decided to find out what induces the nuclear localization of GPER, how general this phenomenon is, and what its functional significance is. 28596490 5 24 dep find 789:792 arg1 out 794:796 out 794:796 out 794:796 We decided to find out what induces the nuclear localization of GPER, how general this phenomenon is, and what its functional significance is. 28596490 7 25 theme nucleotide 1211:1220 arg1 polymorphism 1222:1233 a relatively common single nucleotide polymorphism 1184:1233 a relatively common single nucleotide polymorphism 1184:1233 Surveying a small set of CAFs from breast cancer biopsies, we found that a relatively common single nucleotide polymorphism, which results in the expression of a GPER variant with the amino acid substitution P16L, is associated with the nuclear localization of GPER. 28596490 7 26 from biopsies 1160:1167 arg1 CAFs 1136:1139 CAFs 1136:1139 CAFs from breast cancer biopsies 1136:1167 Surveying a small set of CAFs from breast cancer biopsies, we found that a relatively common single nucleotide polymorphism, which results in the expression of a GPER variant with the amino acid substitution P16L, is associated with the nuclear localization of GPER. 28596490 7 26 from biopsies 1160:1167 arg1 set 1129:1131 a small set 1121:1131 a small set of CAFs from breast cancer biopsies 1121:1167 Surveying a small set of CAFs from breast cancer biopsies, we found that a relatively common single nucleotide polymorphism, which results in the expression of a GPER variant with the amino acid substitution P16L, is associated with the nuclear localization of GPER. 28596490 2 27 theme carcinoma 407:415 arg1 cells 417:421 carcinoma cells 407:421 carcinoma cells 407:421 For breast cancer, the contribution of GPER to promoting the proliferation and migration of both carcinoma cells and cancer-associated fibroblasts (CAFs) in response to estrogen and other agonists has extensively been investigated. 28596490 5 28 theme nuclear 815:821 arg1 localization 823:834 the nuclear localization 811:834 the nuclear localization of GPER 811:842 We decided to find out what induces the nuclear localization of GPER, how general this phenomenon is, and what its functional significance is. 28596490 6 29 theme GPER 980:983 arg1 glycosylation 963:975 N-linked glycosylation 954:975 N-linked glycosylation of GPER 954:983 We discovered that interfering with N-linked glycosylation of GPER, either by mutation of the predicted glycosylation sites or pharmacologically with tunicamycin, drives GPER into the nucleus. 28596490 4 30 theme genes 737:741 arg1 sequences 701:709 regulatory sequences 690:709 regulatory sequences of cancer-relevant target genes 690:741 Moreover, this nuclear GPER was shown to bind regulatory sequences of cancer-relevant target genes and to induce their expression. 28596490 10 31 theme factors 1672:1678 arg1 secretion 1649:1657 the secretion 1645:1657 the secretion of paracrine factors that promote the migration of carcinoma cells 1645:1724 In CAFs, it induces the secretion of paracrine factors that promote the migration of carcinoma cells. 28596490 11 32 theme risk 1798:1801 arg1 factor 1803:1808 a risk factor 1796:1808 a risk factor for breast cancer 1796:1826 This raises the possibility that the GPER P16L polymorphism could be a risk factor for breast cancer. 28596490 11 32 theme risk 1798:1801 arg1 polymorphism 1774:1785 the GPER P16L polymorphism 1760:1785 the GPER P16L polymorphism 1760:1785 This raises the possibility that the GPER P16L polymorphism could be a risk factor for breast cancer. 28596490 7 33 theme GPER 1273:1276 arg1 variant 1278:1284 a GPER variant 1271:1284 a GPER variant with the amino acid substitution P16L 1271:1322 Surveying a small set of CAFs from breast cancer biopsies, we found that a relatively common single nucleotide polymorphism, which results in the expression of a GPER variant with the amino acid substitution P16L, is associated with the nuclear localization of GPER. 28596490 7 34 theme acid 1301:1304 arg1 substitution 1306:1317 the amino acid substitution P16L 1291:1322 the amino acid substitution P16L 1291:1322 Surveying a small set of CAFs from breast cancer biopsies, we found that a relatively common single nucleotide polymorphism, which results in the expression of a GPER variant with the amino acid substitution P16L, is associated with the nuclear localization of GPER. 28596490 7 35 theme cancer 1153:1158 arg1 biopsies 1160:1167 breast cancer biopsies 1146:1167 breast cancer biopsies 1146:1167 Surveying a small set of CAFs from breast cancer biopsies, we found that a relatively common single nucleotide polymorphism, which results in the expression of a GPER variant with the amino acid substitution P16L, is associated with the nuclear localization of GPER. 28596490 8 36 with GPER 1378:1381 arg1 P16L 1388:1391 P16L 1388:1391 P16L 1388:1391 GPER with P16L fails to be glycosylated, presumably because of a conformational effect on the nearby glycosylation sites. 28596490 6 37 gly glycosylation 963:975 arg1 GPER 980:983 GPER 980:983 GPER 980:983 We discovered that interfering with N-linked glycosylation of GPER, either by mutation of the predicted glycosylation sites or pharmacologically with tunicamycin, drives GPER into the nucleus. 28596490 7 38 theme GPER 1372:1375 arg1 localization 1356:1367 the nuclear localization 1344:1367 the nuclear localization of GPER 1344:1375 Surveying a small set of CAFs from breast cancer biopsies, we found that a relatively common single nucleotide polymorphism, which results in the expression of a GPER variant with the amino acid substitution P16L, is associated with the nuclear localization of GPER. 28596490 5 39 theme GPER 839:842 arg1 localization 823:834 the nuclear localization 811:834 the nuclear localization of GPER 811:842 We decided to find out what induces the nuclear localization of GPER, how general this phenomenon is, and what its functional significance is. 28596490 11 40 theme P16L 1769:1772 arg1 factor 1803:1808 a risk factor 1796:1808 a risk factor for breast cancer 1796:1826 This raises the possibility that the GPER P16L polymorphism could be a risk factor for breast cancer. 28596490 11 40 theme P16L 1769:1772 arg1 polymorphism 1774:1785 the GPER P16L polymorphism 1760:1785 the GPER P16L polymorphism 1760:1785 This raises the possibility that the GPER P16L polymorphism could be a risk factor for breast cancer. 28596490 7 41 with variant 1278:1284 arg1 substitution 1306:1317 the amino acid substitution P16L 1291:1322 the amino acid substitution P16L 1291:1322 Surveying a small set of CAFs from breast cancer biopsies, we found that a relatively common single nucleotide polymorphism, which results in the expression of a GPER variant with the amino acid substitution P16L, is associated with the nuclear localization of GPER. 28596490 8 42 theme conformational 1443:1456 arg1 effect 1458:1463 a conformational effect 1441:1463 a conformational effect on the nearby glycosylation sites 1441:1497 GPER with P16L fails to be glycosylated, presumably because of a conformational effect on the nearby glycosylation sites. 28596490 6 43 dep drives 1081:1086 arg1 interfering 937:947 interfering 937:947 interfering with N-linked glycosylation of GPER, either by mutation of the predicted glycosylation sites or pharmacologically with tunicamycin 937:1078 We discovered that interfering with N-linked glycosylation of GPER, either by mutation of the predicted glycosylation sites or pharmacologically with tunicamycin, drives GPER into the nucleus. 28596490 7 44 theme breast 1146:1151 arg1 biopsies 1160:1167 breast cancer biopsies 1146:1167 breast cancer biopsies 1146:1167 Surveying a small set of CAFs from breast cancer biopsies, we found that a relatively common single nucleotide polymorphism, which results in the expression of a GPER variant with the amino acid substitution P16L, is associated with the nuclear localization of GPER. 28596490 10 45 theme cells 1720:1724 arg1 migration 1697:1705 the migration 1693:1705 the migration of carcinoma cells 1693:1724 In CAFs, it induces the secretion of paracrine factors that promote the migration of carcinoma cells. 28596490 7 46 theme variant 1278:1284 arg1 expression 1257:1266 the expression 1253:1266 the expression of a GPER variant with the amino acid substitution P16L 1253:1322 Surveying a small set of CAFs from breast cancer biopsies, we found that a relatively common single nucleotide polymorphism, which results in the expression of a GPER variant with the amino acid substitution P16L, is associated with the nuclear localization of GPER. 28596490 6 47 theme N-linked 954:961 arg1 glycosylation 963:975 N-linked glycosylation 954:975 N-linked glycosylation of GPER 954:983 We discovered that interfering with N-linked glycosylation of GPER, either by mutation of the predicted glycosylation sites or pharmacologically with tunicamycin, drives GPER into the nucleus. 28596490 1 48 theme membrane-associated 226:244 arg1 receptor 255:262 a membrane-associated estrogen receptor 224:262 a membrane-associated estrogen receptor of the family of G-protein coupled receptors 224:307 GPER is a membrane-associated estrogen receptor of the family of G-protein coupled receptors. 28596490 1 48 theme membrane-associated 226:244 arg1 GPER 216:219 GPER 216:219 GPER 216:219 GPER is a membrane-associated estrogen receptor of the family of G-protein coupled receptors. 28596490 10 49 theme paracrine 1662:1670 arg1 factors 1672:1678 paracrine factors 1662:1678 paracrine factors that promote the migration of carcinoma cells 1662:1724 In CAFs, it induces the secretion of paracrine factors that promote the migration of carcinoma cells. 28596490 2 50 theme fibroblasts 445:455 arg1 migration 389:397 migration 389:397 migration 389:397 For breast cancer, the contribution of GPER to promoting the proliferation and migration of both carcinoma cells and cancer-associated fibroblasts (CAFs) in response to estrogen and other agonists has extensively been investigated. 28596490 2 50 theme fibroblasts 445:455 arg1 proliferation 371:383 proliferation 371:383 proliferation 371:383 For breast cancer, the contribution of GPER to promoting the proliferation and migration of both carcinoma cells and cancer-associated fibroblasts (CAFs) in response to estrogen and other agonists has extensively been investigated. 28596490 2 51 theme other 492:496 arg1 agonists 498:505 other agonists 492:505 other agonists 492:505 For breast cancer, the contribution of GPER to promoting the proliferation and migration of both carcinoma cells and cancer-associated fibroblasts (CAFs) in response to estrogen and other agonists has extensively been investigated. 28596490 0 52 theme paracrine 153:161 arg1 signaling 163:171 paracrine signaling 153:171 paracrine signaling between stroma and breast carcinoma cells 153:213 A genetic polymorphism repurposes the G-protein coupled and membrane-associated estrogen receptor GPER to a transcription factor-like molecule promoting paracrine signaling between stroma and breast carcinoma cells. 28596490 6 53 link N-linked 954:961 arg1 glycosylation 963:975 N-linked glycosylation 954:975 N-linked glycosylation of GPER 954:983 We discovered that interfering with N-linked glycosylation of GPER, either by mutation of the predicted glycosylation sites or pharmacologically with tunicamycin, drives GPER into the nucleus. 28596490 5 54 theme general 849:855 arg1 phenomenon 862:871 this phenomenon 857:871 general this phenomenon 849:871 We decided to find out what induces the nuclear localization of GPER, how general this phenomenon is, and what its functional significance is. 28596490 1 55 theme estrogen 246:253 arg1 receptor 255:262 a membrane-associated estrogen receptor 224:262 a membrane-associated estrogen receptor of the family of G-protein coupled receptors 224:307 GPER is a membrane-associated estrogen receptor of the family of G-protein coupled receptors. 28596490 1 55 theme estrogen 246:253 arg1 GPER 216:219 GPER 216:219 GPER 216:219 GPER is a membrane-associated estrogen receptor of the family of G-protein coupled receptors. 28596490 6 56 theme sites 1036:1040 arg1 mutation 996:1003 mutation 996:1003 mutation of the predicted glycosylation sites 996:1040 We discovered that interfering with N-linked glycosylation of GPER, either by mutation of the predicted glycosylation sites or pharmacologically with tunicamycin, drives GPER into the nucleus. 28596490 4 57 theme target 730:735 arg1 genes 737:741 cancer-relevant target genes 714:741 cancer-relevant target genes 714:741 Moreover, this nuclear GPER was shown to bind regulatory sequences of cancer-relevant target genes and to induce their expression. 28596490 7 58 theme CAFs 1136:1139 arg1 CAFs 1136:1139 CAFs 1136:1139 CAFs from breast cancer biopsies 1136:1167 Surveying a small set of CAFs from breast cancer biopsies, we found that a relatively common single nucleotide polymorphism, which results in the expression of a GPER variant with the amino acid substitution P16L, is associated with the nuclear localization of GPER. 28596490 7 58 theme CAFs 1136:1139 arg1 set 1129:1131 a small set 1121:1131 a small set of CAFs from breast cancer biopsies 1121:1167 Surveying a small set of CAFs from breast cancer biopsies, we found that a relatively common single nucleotide polymorphism, which results in the expression of a GPER variant with the amino acid substitution P16L, is associated with the nuclear localization of GPER. 28596490 11 59 theme GPER 1764:1767 arg1 factor 1803:1808 a risk factor 1796:1808 a risk factor for breast cancer 1796:1826 This raises the possibility that the GPER P16L polymorphism could be a risk factor for breast cancer. 28596490 11 59 theme GPER 1764:1767 arg1 polymorphism 1774:1785 the GPER P16L polymorphism 1760:1785 the GPER P16L polymorphism 1760:1785 This raises the possibility that the GPER P16L polymorphism could be a risk factor for breast cancer. 28596490 7 60 theme nuclear 1348:1354 arg1 localization 1356:1367 the nuclear localization 1344:1367 the nuclear localization of GPER 1344:1375 Surveying a small set of CAFs from breast cancer biopsies, we found that a relatively common single nucleotide polymorphism, which results in the expression of a GPER variant with the amino acid substitution P16L, is associated with the nuclear localization of GPER. 28596490 4 61 theme cancer-relevant 714:728 arg1 genes 737:741 cancer-relevant target genes 714:741 cancer-relevant target genes 714:741 Moreover, this nuclear GPER was shown to bind regulatory sequences of cancer-relevant target genes and to induce their expression. 28596490 7 62 from set 1129:1131 arg1 biopsies 1160:1167 breast cancer biopsies 1146:1167 breast cancer biopsies 1146:1167 Surveying a small set of CAFs from breast cancer biopsies, we found that a relatively common single nucleotide polymorphism, which results in the expression of a GPER variant with the amino acid substitution P16L, is associated with the nuclear localization of GPER. 28596490 0 63 theme breast 192:197 arg1 cells 209:213 breast carcinoma cells 192:213 breast carcinoma cells 192:213 A genetic polymorphism repurposes the G-protein coupled and membrane-associated estrogen receptor GPER to a transcription factor-like molecule promoting paracrine signaling between stroma and breast carcinoma cells. 28596490 9 64 theme transcription 1603:1615 arg1 factor 1617:1622 an estrogen-stimulated transcription factor 1580:1622 an estrogen-stimulated transcription factor 1580:1622 GPER P16L is defective for membrane-associated signaling, but instead acts like an estrogen-stimulated transcription factor. 28596490 3 65 theme CAFs 638:641 arg1 isolate 620:626 one isolate 616:626 one isolate of breast CAFs 616:641 Intriguingly, GPER was previously found to be localized to the nucleus in one isolate of breast CAFs. 28596490 11 66 theme breast 1814:1819 arg1 cancer 1821:1826 breast cancer 1814:1826 breast cancer 1814:1826 This raises the possibility that the GPER P16L polymorphism could be a risk factor for breast cancer. 28596490 6 67 theme glycosylation 1022:1034 arg1 sites 1036:1040 the predicted glycosylation sites 1008:1040 the predicted glycosylation sites 1008:1040 We discovered that interfering with N-linked glycosylation of GPER, either by mutation of the predicted glycosylation sites or pharmacologically with tunicamycin, drives GPER into the nucleus. 28596490 2 68 theme GPER 349:352 arg1 contribution 333:344 the contribution 329:344 the contribution of GPER to promoting the proliferation and migration of both carcinoma cells and cancer-associated fibroblasts (CAFs) in response to estrogen and other agonists 329:505 For breast cancer, the contribution of GPER to promoting the proliferation and migration of both carcinoma cells and cancer-associated fibroblasts (CAFs) in response to estrogen and other agonists has extensively been investigated. 28596490 6 69 theme predicted 1012:1020 arg1 sites 1036:1040 the predicted glycosylation sites 1008:1040 the predicted glycosylation sites 1008:1040 We discovered that interfering with N-linked glycosylation of GPER, either by mutation of the predicted glycosylation sites or pharmacologically with tunicamycin, drives GPER into the nucleus. 28596490 0 70 theme estrogen 80:87 arg1 receptor 89:96 the G-protein coupled and membrane-associated estrogen receptor 34:96 receptor 89:96 A genetic polymorphism repurposes the G-protein coupled and membrane-associated estrogen receptor GPER to a transcription factor-like molecule promoting paracrine signaling between stroma and breast carcinoma cells. 28596490 2 71 theme cancer-associated 427:443 arg1 fibroblasts 445:455 cancer-associated fibroblasts 427:455 cancer-associated fibroblasts (CAFs) 427:462 For breast cancer, the contribution of GPER to promoting the proliferation and migration of both carcinoma cells and cancer-associated fibroblasts (CAFs) in response to estrogen and other agonists has extensively been investigated. 28596490 2 71 theme cancer-associated 427:443 arg1 CAFs 458:461 CAFs 458:461 CAFs 458:461 For breast cancer, the contribution of GPER to promoting the proliferation and migration of both carcinoma cells and cancer-associated fibroblasts (CAFs) in response to estrogen and other agonists has extensively been investigated. 28596490 6 72 gly glycosylation 1022:1034 arg2 sites 1036:1040 the predicted glycosylation sites 1008:1040 the predicted glycosylation sites 1008:1040 We discovered that interfering with N-linked glycosylation of GPER, either by mutation of the predicted glycosylation sites or pharmacologically with tunicamycin, drives GPER into the nucleus. 28596490 4 73 theme regulatory 690:699 arg1 sequences 701:709 regulatory sequences 690:709 regulatory sequences of cancer-relevant target genes 690:741 Moreover, this nuclear GPER was shown to bind regulatory sequences of cancer-relevant target genes and to induce their expression. 28596490 0 74 theme membrane-associated 60:78 arg1 receptor 89:96 the G-protein coupled and membrane-associated estrogen receptor 34:96 receptor 89:96 A genetic polymorphism repurposes the G-protein coupled and membrane-associated estrogen receptor GPER to a transcription factor-like molecule promoting paracrine signaling between stroma and breast carcinoma cells. 28596490 3 75 theme breast 631:636 arg1 CAFs 638:641 breast CAFs 631:641 breast CAFs 631:641 Intriguingly, GPER was previously found to be localized to the nucleus in one isolate of breast CAFs. 28596490 10 76 theme carcinoma 1710:1718 arg1 cells 1720:1724 carcinoma cells 1710:1724 carcinoma cells 1710:1724 In CAFs, it induces the secretion of paracrine factors that promote the migration of carcinoma cells. 28596490 9 77 theme estrogen-stimulated 1583:1601 arg1 factor 1617:1622 an estrogen-stimulated transcription factor 1580:1622 an estrogen-stimulated transcription factor 1580:1622 GPER P16L is defective for membrane-associated signaling, but instead acts like an estrogen-stimulated transcription factor. 28596490 1 78 theme family 271:276 arg1 receptor 255:262 a membrane-associated estrogen receptor 224:262 a membrane-associated estrogen receptor of the family of G-protein coupled receptors 224:307 GPER is a membrane-associated estrogen receptor of the family of G-protein coupled receptors. 28596490 1 78 theme family 271:276 arg1 GPER 216:219 GPER 216:219 GPER 216:219 GPER is a membrane-associated estrogen receptor of the family of G-protein coupled receptors. 26807597 10 0 theme multiple 1482:1489 arg1 sites 1491:1495 multiple sites 1482:1495 multiple sites 1482:1495 Our results suggest that O-GlcNAc cycling enzymes can employ a similar mechanism to react with other protein substrates on multiple sites. 26807597 9 1 theme glycosylated 1276:1287 arg1 CTD 1289:1291 glycosylated CTD 1276:1291 glycosylated CTD 1276:1291 Moreover, removal of O-GlcNAc from glycosylated CTD is also distributive and is independent of O-GlcNAcylation level. 26807597 10 2 theme cycling 1393:1399 arg1 enzymes 1401:1407 O-GlcNAc cycling enzymes 1384:1407 O-GlcNAc cycling enzymes 1384:1407 Our results suggest that O-GlcNAc cycling enzymes can employ a similar mechanism to react with other protein substrates on multiple sites. 26807597 3 3 theme dynamic 481:487 arg1 O-GlcNAcylation 489:503 dynamic O-GlcNAcylation 481:503 dynamic O-GlcNAcylation 481:503 One approach to understanding the function of glycosylated Pol II is to determine the mechanism of dynamic O-GlcNAcylation on the CTD. 26807597 5 4 theme than 698:701 arg1 half 703:706 more than half 693:706 more than half of the N-terminal domain of O-GlcNAc transferase (OGT) 693:761 Efficient glycosylation requires a minimum of 20 heptad repeats of the CTD and more than half of the N-terminal domain of O-GlcNAc transferase (OGT). 26807597 9 5 theme level 1352:1356 arg1 independent 1321:1331 independent 1321:1331 independent 1321:1331 Moreover, removal of O-GlcNAc from glycosylated CTD is also distributive and is independent of O-GlcNAcylation level. 26807597 0 6 theme Polymerase 79:88 arg1 Polymerase 79:88 RNA Polymerase II 75:91 RNA Polymerase II 75:91 Distributive O-GlcNAcylation on the Highly Repetitive C-Terminal Domain of RNA Polymerase II. 26807597 0 6 theme Polymerase 79:88 arg1 Domain 65:70 the Highly Repetitive C-Terminal Domain 32:70 the Highly Repetitive C-Terminal Domain of RNA Polymerase II 32:91 Distributive O-GlcNAcylation on the Highly Repetitive C-Terminal Domain of RNA Polymerase II. 26807597 0 7 from O-GlcNAcylation 13:27 arg1 Polymerase 79:88 RNA Polymerase II 75:91 RNA Polymerase II 75:91 Distributive O-GlcNAcylation on the Highly Repetitive C-Terminal Domain of RNA Polymerase II. 26807597 0 7 from O-GlcNAcylation 13:27 arg1 Domain 65:70 the Highly Repetitive C-Terminal Domain 32:70 the Highly Repetitive C-Terminal Domain of RNA Polymerase II 32:91 Distributive O-GlcNAcylation on the Highly Repetitive C-Terminal Domain of RNA Polymerase II. 26807597 5 8 theme Efficient 614:622 arg1 glycosylation 624:636 Efficient glycosylation 614:636 Efficient glycosylation 614:636 Efficient glycosylation requires a minimum of 20 heptad repeats of the CTD and more than half of the N-terminal domain of O-GlcNAc transferase (OGT). 26807597 3 9 theme O-GlcNAcylation 489:503 arg1 mechanism 468:476 the mechanism 464:476 the mechanism of dynamic O-GlcNAcylation on the CTD 464:514 One approach to understanding the function of glycosylated Pol II is to determine the mechanism of dynamic O-GlcNAcylation on the CTD. 26807597 4 10 theme Pol 546:548 arg1 CTD 553:555 the Pol II CTD 542:555 the Pol II CTD 542:555 Here, we discovered that the Pol II CTD can be extensively O-GlcNAcylated in vitro and in cells. 26807597 4 10 theme Pol 546:548 arg1 O-GlcNAcylated 576:589 O-GlcNAcylated 576:589 O-GlcNAcylated 576:589 Here, we discovered that the Pol II CTD can be extensively O-GlcNAcylated in vitro and in cells. 26807597 5 11 theme CTD 685:687 arg1 repeats 670:676 20 heptad repeats 660:676 20 heptad repeats of the CTD 660:687 Efficient glycosylation requires a minimum of 20 heptad repeats of the CTD and more than half of the N-terminal domain of O-GlcNAc transferase (OGT). 26807597 2 12 link O-linked 266:273 arg1 O-GlcNAc 296:303 O-GlcNAc 296:303 O-GlcNAc 296:303 Human RNA polymerase II (Pol II) is extensively modified by O-linked N-acetylglucosamine (O-GlcNAc) on its unique C-terminal domain (CTD), which consists of 52 heptad repeats. 26807597 2 12 link O-linked 266:273 arg1 N-acetylglucosamine 275:293 O-linked N-acetylglucosamine 266:293 O-linked N-acetylglucosamine (O-GlcNAc) on its unique C-terminal domain (CTD), which consists of 52 heptad repeats 266:379 Human RNA polymerase II (Pol II) is extensively modified by O-linked N-acetylglucosamine (O-GlcNAc) on its unique C-terminal domain (CTD), which consists of 52 heptad repeats. 26807597 8 13 with CTD 1206:1208 arg1 distributions 1226:1238 nonuniform distributions 1215:1238 nonuniform distributions 1215:1238 Our data suggest that initial O-GlcNAcylation can take place either on the proximal or on the distal region of the CTD, and subsequent glycosylation occurs similarly over the entire CTD with nonuniform distributions. 26807597 11 14 theme regulatory 1554:1563 arg1 mechanism 1565:1573 another regulatory mechanism 1546:1573 another regulatory mechanism of transcription 1546:1590 Distributive O-GlcNAcylation on Pol II provides another regulatory mechanism of transcription in response to fluctuating cellular conditions. 26807597 5 15 theme more 693:696 arg1 half 703:706 more than half 693:706 more than half of the N-terminal domain of O-GlcNAc transferase (OGT) 693:761 Efficient glycosylation requires a minimum of 20 heptad repeats of the CTD and more than half of the N-terminal domain of O-GlcNAc transferase (OGT). 26807597 8 16 theme nonuniform 1215:1224 arg1 distributions 1226:1238 nonuniform distributions 1215:1238 nonuniform distributions 1215:1238 Our data suggest that initial O-GlcNAcylation can take place either on the proximal or on the distal region of the CTD, and subsequent glycosylation occurs similarly over the entire CTD with nonuniform distributions. 26807597 1 17 theme transcriptional 178:192 arg1 regulation 194:203 transcriptional regulation 178:203 transcriptional regulation 178:203 O-GlcNAcylation is a nutrient-responsive glycosylation that plays a pivotal role in transcriptional regulation. 26807597 5 18 theme transferase 745:755 arg1 domain 726:731 the N-terminal domain 711:731 the N-terminal domain of O-GlcNAc transferase (OGT) 711:761 Efficient glycosylation requires a minimum of 20 heptad repeats of the CTD and more than half of the N-terminal domain of O-GlcNAc transferase (OGT). 26807597 5 18 theme transferase 745:755 arg1 transferase 745:755 O-GlcNAc transferase 736:755 O-GlcNAc transferase (OGT) 736:761 Efficient glycosylation requires a minimum of 20 heptad repeats of the CTD and more than half of the N-terminal domain of O-GlcNAc transferase (OGT). 26807597 3 19 dep approach 386:393 arg1 understanding 398:410 understanding 398:410 to understanding the function of glycosylated Pol II 395:446 One approach to understanding the function of glycosylated Pol II is to determine the mechanism of dynamic O-GlcNAcylation on the CTD. 26807597 9 20 gly glycosylated 1276:1287 arg1 CTD 1289:1291 glycosylated CTD 1276:1291 glycosylated CTD 1276:1291 Moreover, removal of O-GlcNAc from glycosylated CTD is also distributive and is independent of O-GlcNAcylation level. 26807597 3 21 theme glycosylated 428:439 arg1 II 445:446 glycosylated Pol II 428:446 glycosylated Pol II 428:446 One approach to understanding the function of glycosylated Pol II is to determine the mechanism of dynamic O-GlcNAcylation on the CTD. 26807597 8 22 theme distal 1118:1123 arg1 region 1125:1130 the distal region 1114:1130 the distal region of the CTD 1114:1141 Our data suggest that initial O-GlcNAcylation can take place either on the proximal or on the distal region of the CTD, and subsequent glycosylation occurs similarly over the entire CTD with nonuniform distributions. 26807597 5 23 theme N-terminal 715:724 arg1 domain 726:731 the N-terminal domain 711:731 the N-terminal domain of O-GlcNAc transferase (OGT) 711:761 Efficient glycosylation requires a minimum of 20 heptad repeats of the CTD and more than half of the N-terminal domain of O-GlcNAc transferase (OGT). 26807597 5 23 theme N-terminal 715:724 arg1 transferase 745:755 O-GlcNAc transferase 736:755 O-GlcNAc transferase (OGT) 736:761 Efficient glycosylation requires a minimum of 20 heptad repeats of the CTD and more than half of the N-terminal domain of O-GlcNAc transferase (OGT). 26807597 2 24 theme C-terminal 320:329 arg1 CTD 339:341 CTD 339:341 CTD 339:341 Human RNA polymerase II (Pol II) is extensively modified by O-linked N-acetylglucosamine (O-GlcNAc) on its unique C-terminal domain (CTD), which consists of 52 heptad repeats. 26807597 2 24 theme C-terminal 320:329 arg1 domain 331:336 its unique C-terminal domain 309:336 its unique C-terminal domain (CTD) 309:342 Human RNA polymerase II (Pol II) is extensively modified by O-linked N-acetylglucosamine (O-GlcNAc) on its unique C-terminal domain (CTD), which consists of 52 heptad repeats. 26807597 10 25 theme protein 1460:1466 arg1 substrates 1468:1477 other protein substrates 1454:1477 other protein substrates on multiple sites 1454:1495 Our results suggest that O-GlcNAc cycling enzymes can employ a similar mechanism to react with other protein substrates on multiple sites. 26807597 2 26 theme heptad 366:371 arg1 repeats 373:379 52 heptad repeats 363:379 52 heptad repeats 363:379 Human RNA polymerase II (Pol II) is extensively modified by O-linked N-acetylglucosamine (O-GlcNAc) on its unique C-terminal domain (CTD), which consists of 52 heptad repeats. 26807597 0 27 theme Distributive 0:11 arg1 O-GlcNAcylation 13:27 Distributive O-GlcNAcylation 0:27 Distributive O-GlcNAcylation on the Highly Repetitive C-Terminal Domain of RNA Polymerase II 0:91 Distributive O-GlcNAcylation on the Highly Repetitive C-Terminal Domain of RNA Polymerase II. 26807597 9 28 theme O-GlcNAc 1262:1269 arg1 removal 1251:1257 removal 1251:1257 removal of O-GlcNAc from glycosylated CTD 1251:1291 Moreover, removal of O-GlcNAc from glycosylated CTD is also distributive and is independent of O-GlcNAcylation level. 26807597 3 29 from mechanism 468:476 arg1 CTD 512:514 the CTD 508:514 the CTD 508:514 One approach to understanding the function of glycosylated Pol II is to determine the mechanism of dynamic O-GlcNAcylation on the CTD. 26807597 2 30 theme unique 313:318 arg1 CTD 339:341 CTD 339:341 CTD 339:341 Human RNA polymerase II (Pol II) is extensively modified by O-linked N-acetylglucosamine (O-GlcNAc) on its unique C-terminal domain (CTD), which consists of 52 heptad repeats. 26807597 2 30 theme unique 313:318 arg1 domain 331:336 its unique C-terminal domain 309:336 its unique C-terminal domain (CTD) 309:342 Human RNA polymerase II (Pol II) is extensively modified by O-linked N-acetylglucosamine (O-GlcNAc) on its unique C-terminal domain (CTD), which consists of 52 heptad repeats. 26807597 4 31 from cells 607:611 arg1 O-GlcNAcylated 576:589 O-GlcNAcylated 576:589 O-GlcNAcylated 576:589 Here, we discovered that the Pol II CTD can be extensively O-GlcNAcylated in vitro and in cells. 26807597 10 32 theme O-GlcNAc 1384:1391 arg1 enzymes 1401:1407 O-GlcNAc cycling enzymes 1384:1407 O-GlcNAc cycling enzymes 1384:1407 Our results suggest that O-GlcNAc cycling enzymes can employ a similar mechanism to react with other protein substrates on multiple sites. 26807597 11 33 theme Distributive 1498:1509 arg1 O-GlcNAcylation 1511:1525 Distributive O-GlcNAcylation 1498:1525 Distributive O-GlcNAcylation on Pol II 1498:1535 Distributive O-GlcNAcylation on Pol II provides another regulatory mechanism of transcription in response to fluctuating cellular conditions. 26807597 5 34 theme heptad 663:668 arg1 repeats 670:676 20 heptad repeats 660:676 20 heptad repeats of the CTD 660:687 Efficient glycosylation requires a minimum of 20 heptad repeats of the CTD and more than half of the N-terminal domain of O-GlcNAc transferase (OGT). 26807597 8 35 theme CTD 1139:1141 arg1 region 1125:1130 the distal region 1114:1130 the distal region of the CTD 1114:1141 Our data suggest that initial O-GlcNAcylation can take place either on the proximal or on the distal region of the CTD, and subsequent glycosylation occurs similarly over the entire CTD with nonuniform distributions. 26807597 9 36 from CTD 1289:1291 arg1 removal 1251:1257 removal 1251:1257 removal of O-GlcNAc from glycosylated CTD 1251:1291 Moreover, removal of O-GlcNAc from glycosylated CTD is also distributive and is independent of O-GlcNAcylation level. 26807597 7 37 gly glycosylation 910:922 arg1 CTD 940:942 the periodic CTD 927:942 the periodic CTD 927:942 Surprisingly, glycosylation on the periodic CTD follows a distributive mechanism, resulting in highly heterogeneous glycoforms. 26807597 5 38 theme repeats 670:676 arg1 minimum 649:655 a minimum 647:655 a minimum of 20 heptad repeats of the CTD 647:687 Efficient glycosylation requires a minimum of 20 heptad repeats of the CTD and more than half of the N-terminal domain of O-GlcNAc transferase (OGT). 26807597 5 38 theme repeats 670:676 arg1 half 703:706 more than half 693:706 more than half of the N-terminal domain of O-GlcNAc transferase (OGT) 693:761 Efficient glycosylation requires a minimum of 20 heptad repeats of the CTD and more than half of the N-terminal domain of O-GlcNAc transferase (OGT). 26807597 2 39 theme Human 206:210 arg1 polymerase 216:225 Human RNA polymerase II 206:228 Human RNA polymerase II (Pol II) 206:237 Human RNA polymerase II (Pol II) is extensively modified by O-linked N-acetylglucosamine (O-GlcNAc) on its unique C-terminal domain (CTD), which consists of 52 heptad repeats. 26807597 2 39 theme Human 206:210 arg1 II 235:236 Pol II 231:236 Pol II 231:236 Human RNA polymerase II (Pol II) is extensively modified by O-linked N-acetylglucosamine (O-GlcNAc) on its unique C-terminal domain (CTD), which consists of 52 heptad repeats. 26807597 0 40 theme Repetitive 43:52 arg1 Polymerase 79:88 RNA Polymerase II 75:91 RNA Polymerase II 75:91 Distributive O-GlcNAcylation on the Highly Repetitive C-Terminal Domain of RNA Polymerase II. 26807597 0 40 theme Repetitive 43:52 arg1 Domain 65:70 the Highly Repetitive C-Terminal Domain 32:70 the Highly Repetitive C-Terminal Domain of RNA Polymerase II 32:91 Distributive O-GlcNAcylation on the Highly Repetitive C-Terminal Domain of RNA Polymerase II. 26807597 6 41 theme full-length 879:889 arg1 CTD 891:893 the full-length CTD 875:893 the full-length CTD 875:893 Under conditions of saturated sugar donor, we monitored the attachment of more than 20 residues of O-GlcNAc to the full-length CTD. 26807597 4 42 from vitro 594:598 arg1 CTD 553:555 the Pol II CTD 542:555 the Pol II CTD 542:555 Here, we discovered that the Pol II CTD can be extensively O-GlcNAcylated in vitro and in cells. 26807597 4 42 from vitro 594:598 arg1 O-GlcNAcylated 576:589 O-GlcNAcylated 576:589 O-GlcNAcylated 576:589 Here, we discovered that the Pol II CTD can be extensively O-GlcNAcylated in vitro and in cells. 26807597 3 43 theme Pol 441:443 arg1 II 445:446 glycosylated Pol II 428:446 glycosylated Pol II 428:446 One approach to understanding the function of glycosylated Pol II is to determine the mechanism of dynamic O-GlcNAcylation on the CTD. 26807597 6 44 attach attachment 824:833 arg2 residues 851:858 more than 20 residues 838:858 more than 20 residues of O-GlcNAc 838:870 Under conditions of saturated sugar donor, we monitored the attachment of more than 20 residues of O-GlcNAc to the full-length CTD. 26807597 6 44 attach attachment 824:833 arg1 CTD 891:893 the full-length CTD 875:893 the full-length CTD 875:893 Under conditions of saturated sugar donor, we monitored the attachment of more than 20 residues of O-GlcNAc to the full-length CTD. 26807597 6 44 attach attachment 824:833 arg2 O-GlcNAc 863:870 O-GlcNAc 863:870 O-GlcNAc 863:870 Under conditions of saturated sugar donor, we monitored the attachment of more than 20 residues of O-GlcNAc to the full-length CTD. 26807597 11 45 dep conditions 1628:1637 arg1 response 1595:1602 response 1595:1602 response 1595:1602 Distributive O-GlcNAcylation on Pol II provides another regulatory mechanism of transcription in response to fluctuating cellular conditions. 26807597 10 46 theme similar 1422:1428 arg1 mechanism 1430:1438 a similar mechanism 1420:1438 a similar mechanism to react with other protein substrates on multiple sites 1420:1495 Our results suggest that O-GlcNAc cycling enzymes can employ a similar mechanism to react with other protein substrates on multiple sites. 26807597 6 47 theme donor 800:804 arg1 conditions 770:779 conditions 770:779 conditions of saturated sugar donor 770:804 Under conditions of saturated sugar donor, we monitored the attachment of more than 20 residues of O-GlcNAc to the full-length CTD. 26807597 3 48 theme II 445:446 arg1 function 416:423 the function 412:423 the function of glycosylated Pol II 412:446 One approach to understanding the function of glycosylated Pol II is to determine the mechanism of dynamic O-GlcNAcylation on the CTD. 26807597 5 49 theme O-GlcNAc 736:743 arg1 OGT 758:760 OGT 758:760 OGT 758:760 Efficient glycosylation requires a minimum of 20 heptad repeats of the CTD and more than half of the N-terminal domain of O-GlcNAc transferase (OGT). 26807597 5 49 theme O-GlcNAc 736:743 arg1 transferase 745:755 O-GlcNAc transferase 736:755 O-GlcNAc transferase (OGT) 736:761 Efficient glycosylation requires a minimum of 20 heptad repeats of the CTD and more than half of the N-terminal domain of O-GlcNAc transferase (OGT). 26807597 8 50 theme initial 1046:1052 arg1 O-GlcNAcylation 1054:1068 initial O-GlcNAcylation 1046:1068 initial O-GlcNAcylation 1046:1068 Our data suggest that initial O-GlcNAcylation can take place either on the proximal or on the distal region of the CTD, and subsequent glycosylation occurs similarly over the entire CTD with nonuniform distributions. 26807597 6 51 theme sugar 794:798 arg1 donor 800:804 saturated sugar donor 784:804 saturated sugar donor 784:804 Under conditions of saturated sugar donor, we monitored the attachment of more than 20 residues of O-GlcNAc to the full-length CTD. 26807597 10 52 theme other 1454:1458 arg1 substrates 1468:1477 other protein substrates 1454:1477 other protein substrates on multiple sites 1454:1495 Our results suggest that O-GlcNAc cycling enzymes can employ a similar mechanism to react with other protein substrates on multiple sites. 26807597 1 53 theme nutrient-responsive 115:133 arg1 O-GlcNAcylation 94:108 O-GlcNAcylation 94:108 O-GlcNAcylation 94:108 O-GlcNAcylation is a nutrient-responsive glycosylation that plays a pivotal role in transcriptional regulation. 26807597 1 53 theme nutrient-responsive 115:133 arg1 glycosylation 135:147 a nutrient-responsive glycosylation 113:147 a nutrient-responsive glycosylation that plays a pivotal role in transcriptional regulation 113:203 O-GlcNAcylation is a nutrient-responsive glycosylation that plays a pivotal role in transcriptional regulation. 26807597 0 54 theme C-Terminal 54:63 arg1 Polymerase 79:88 RNA Polymerase II 75:91 RNA Polymerase II 75:91 Distributive O-GlcNAcylation on the Highly Repetitive C-Terminal Domain of RNA Polymerase II. 26807597 0 54 theme C-Terminal 54:63 arg1 Domain 65:70 the Highly Repetitive C-Terminal Domain 32:70 the Highly Repetitive C-Terminal Domain of RNA Polymerase II 32:91 Distributive O-GlcNAcylation on the Highly Repetitive C-Terminal Domain of RNA Polymerase II. 26807597 6 55 theme O-GlcNAc 863:870 arg1 O-GlcNAc 863:870 O-GlcNAc 863:870 O-GlcNAc 863:870 Under conditions of saturated sugar donor, we monitored the attachment of more than 20 residues of O-GlcNAc to the full-length CTD. 26807597 6 55 theme O-GlcNAc 863:870 arg1 residues 851:858 more than 20 residues 838:858 more than 20 residues of O-GlcNAc 838:870 Under conditions of saturated sugar donor, we monitored the attachment of more than 20 residues of O-GlcNAc to the full-length CTD. 26807597 7 56 theme heterogeneous 998:1010 arg1 glycoforms 1012:1021 highly heterogeneous glycoforms 991:1021 highly heterogeneous glycoforms 991:1021 Surprisingly, glycosylation on the periodic CTD follows a distributive mechanism, resulting in highly heterogeneous glycoforms. 26807597 6 57 theme saturated 784:792 arg1 donor 800:804 saturated sugar donor 784:804 saturated sugar donor 784:804 Under conditions of saturated sugar donor, we monitored the attachment of more than 20 residues of O-GlcNAc to the full-length CTD. 26807597 2 58 theme Pol 231:233 arg1 polymerase 216:225 Human RNA polymerase II 206:228 Human RNA polymerase II (Pol II) 206:237 Human RNA polymerase II (Pol II) is extensively modified by O-linked N-acetylglucosamine (O-GlcNAc) on its unique C-terminal domain (CTD), which consists of 52 heptad repeats. 26807597 2 58 theme Pol 231:233 arg1 II 235:236 Pol II 231:236 Pol II 231:236 Human RNA polymerase II (Pol II) is extensively modified by O-linked N-acetylglucosamine (O-GlcNAc) on its unique C-terminal domain (CTD), which consists of 52 heptad repeats. 26807597 7 59 theme periodic 931:938 arg1 CTD 940:942 the periodic CTD 927:942 the periodic CTD 927:942 Surprisingly, glycosylation on the periodic CTD follows a distributive mechanism, resulting in highly heterogeneous glycoforms. 26807597 11 60 from O-GlcNAcylation 1511:1525 arg1 Pol 1530:1532 Pol II 1530:1535 Pol II 1530:1535 Distributive O-GlcNAcylation on Pol II provides another regulatory mechanism of transcription in response to fluctuating cellular conditions. 26807597 10 61 from substrates 1468:1477 arg1 sites 1491:1495 multiple sites 1482:1495 multiple sites 1482:1495 Our results suggest that O-GlcNAc cycling enzymes can employ a similar mechanism to react with other protein substrates on multiple sites. 26807597 7 62 theme distributive 954:965 arg1 mechanism 967:975 a distributive mechanism 952:975 a distributive mechanism 952:975 Surprisingly, glycosylation on the periodic CTD follows a distributive mechanism, resulting in highly heterogeneous glycoforms. 26807597 2 63 theme O-linked 266:273 arg1 O-GlcNAc 296:303 O-GlcNAc 296:303 O-GlcNAc 296:303 Human RNA polymerase II (Pol II) is extensively modified by O-linked N-acetylglucosamine (O-GlcNAc) on its unique C-terminal domain (CTD), which consists of 52 heptad repeats. 26807597 2 63 theme O-linked 266:273 arg1 N-acetylglucosamine 275:293 O-linked N-acetylglucosamine 266:293 O-linked N-acetylglucosamine (O-GlcNAc) on its unique C-terminal domain (CTD), which consists of 52 heptad repeats 266:379 Human RNA polymerase II (Pol II) is extensively modified by O-linked N-acetylglucosamine (O-GlcNAc) on its unique C-terminal domain (CTD), which consists of 52 heptad repeats. 26807597 3 64 gly glycosylated 428:439 arg1 II 445:446 glycosylated Pol II 428:446 glycosylated Pol II 428:446 One approach to understanding the function of glycosylated Pol II is to determine the mechanism of dynamic O-GlcNAcylation on the CTD. 26807597 2 65 from N-acetylglucosamine 275:293 arg1 CTD 339:341 CTD 339:341 CTD 339:341 Human RNA polymerase II (Pol II) is extensively modified by O-linked N-acetylglucosamine (O-GlcNAc) on its unique C-terminal domain (CTD), which consists of 52 heptad repeats. 26807597 2 65 from N-acetylglucosamine 275:293 arg1 domain 331:336 its unique C-terminal domain 309:336 its unique C-terminal domain (CTD) 309:342 Human RNA polymerase II (Pol II) is extensively modified by O-linked N-acetylglucosamine (O-GlcNAc) on its unique C-terminal domain (CTD), which consists of 52 heptad repeats. 26807597 8 66 theme entire 1199:1204 arg1 CTD 1206:1208 the entire CTD 1195:1208 the entire CTD with nonuniform distributions 1195:1238 Our data suggest that initial O-GlcNAcylation can take place either on the proximal or on the distal region of the CTD, and subsequent glycosylation occurs similarly over the entire CTD with nonuniform distributions. 26807597 5 67 theme domain 726:731 arg1 minimum 649:655 a minimum 647:655 a minimum of 20 heptad repeats of the CTD 647:687 Efficient glycosylation requires a minimum of 20 heptad repeats of the CTD and more than half of the N-terminal domain of O-GlcNAc transferase (OGT). 26807597 5 67 theme domain 726:731 arg1 half 703:706 more than half 693:706 more than half of the N-terminal domain of O-GlcNAc transferase (OGT) 693:761 Efficient glycosylation requires a minimum of 20 heptad repeats of the CTD and more than half of the N-terminal domain of O-GlcNAc transferase (OGT). 26807597 8 68 theme subsequent 1148:1157 arg1 glycosylation 1159:1171 subsequent glycosylation 1148:1171 subsequent glycosylation 1148:1171 Our data suggest that initial O-GlcNAcylation can take place either on the proximal or on the distal region of the CTD, and subsequent glycosylation occurs similarly over the entire CTD with nonuniform distributions. 26807597 11 69 theme transcription 1578:1590 arg1 mechanism 1565:1573 another regulatory mechanism 1546:1573 another regulatory mechanism of transcription 1546:1590 Distributive O-GlcNAcylation on Pol II provides another regulatory mechanism of transcription in response to fluctuating cellular conditions. 26807597 11 70 theme cellular 1619:1626 arg1 conditions 1628:1637 fluctuating cellular conditions 1607:1637 fluctuating cellular conditions 1607:1637 Distributive O-GlcNAcylation on Pol II provides another regulatory mechanism of transcription in response to fluctuating cellular conditions. 26807597 0 71 theme RNA 75:77 arg1 Polymerase 79:88 RNA Polymerase II 75:91 RNA Polymerase II 75:91 Distributive O-GlcNAcylation on the Highly Repetitive C-Terminal Domain of RNA Polymerase II. 26807597 2 72 theme RNA 212:214 arg1 polymerase 216:225 Human RNA polymerase II 206:228 Human RNA polymerase II (Pol II) 206:237 Human RNA polymerase II (Pol II) is extensively modified by O-linked N-acetylglucosamine (O-GlcNAc) on its unique C-terminal domain (CTD), which consists of 52 heptad repeats. 26807597 2 72 theme RNA 212:214 arg1 II 235:236 Pol II 231:236 Pol II 231:236 Human RNA polymerase II (Pol II) is extensively modified by O-linked N-acetylglucosamine (O-GlcNAc) on its unique C-terminal domain (CTD), which consists of 52 heptad repeats. 26807597 2 73 mod modified 254:261 arg3 N-acetylglucosamine 275:293 O-linked N-acetylglucosamine 266:293 O-linked N-acetylglucosamine (O-GlcNAc) on its unique C-terminal domain (CTD), which consists of 52 heptad repeats 266:379 Human RNA polymerase II (Pol II) is extensively modified by O-linked N-acetylglucosamine (O-GlcNAc) on its unique C-terminal domain (CTD), which consists of 52 heptad repeats. 26807597 2 73 mod modified 254:261 arg1 polymerase 216:225 Human RNA polymerase II 206:228 Human RNA polymerase II (Pol II) 206:237 Human RNA polymerase II (Pol II) is extensively modified by O-linked N-acetylglucosamine (O-GlcNAc) on its unique C-terminal domain (CTD), which consists of 52 heptad repeats. 26807597 2 73 mod modified 254:261 arg3 O-GlcNAc 296:303 O-GlcNAc 296:303 O-GlcNAc 296:303 Human RNA polymerase II (Pol II) is extensively modified by O-linked N-acetylglucosamine (O-GlcNAc) on its unique C-terminal domain (CTD), which consists of 52 heptad repeats. 26807597 2 73 mod modified 254:261 arg1 II 235:236 Pol II 231:236 Pol II 231:236 Human RNA polymerase II (Pol II) is extensively modified by O-linked N-acetylglucosamine (O-GlcNAc) on its unique C-terminal domain (CTD), which consists of 52 heptad repeats. 26807597 7 74 from glycosylation 910:922 arg1 CTD 940:942 the periodic CTD 927:942 the periodic CTD 927:942 Surprisingly, glycosylation on the periodic CTD follows a distributive mechanism, resulting in highly heterogeneous glycoforms. 26807597 11 75 theme fluctuating 1607:1617 arg1 conditions 1628:1637 fluctuating cellular conditions 1607:1637 fluctuating cellular conditions 1607:1637 Distributive O-GlcNAcylation on Pol II provides another regulatory mechanism of transcription in response to fluctuating cellular conditions. 26807597 4 76 from O-GlcNAcylated 576:589 arg1 vitro 594:598 vitro 594:598 vitro 594:598 Here, we discovered that the Pol II CTD can be extensively O-GlcNAcylated in vitro and in cells. 26807597 4 76 from O-GlcNAcylated 576:589 arg1 cells 607:611 cells 607:611 cells 607:611 Here, we discovered that the Pol II CTD can be extensively O-GlcNAcylated in vitro and in cells. 26807597 6 77 theme residues 851:858 arg1 attachment 824:833 the attachment 820:833 the attachment of more than 20 residues of O-GlcNAc to the full-length CTD 820:893 Under conditions of saturated sugar donor, we monitored the attachment of more than 20 residues of O-GlcNAc to the full-length CTD. 26807597 1 78 theme pivotal 162:168 arg1 role 170:173 a pivotal role 160:173 a pivotal role 160:173 O-GlcNAcylation is a nutrient-responsive glycosylation that plays a pivotal role in transcriptional regulation. 26807597 9 79 theme O-GlcNAcylation 1336:1350 arg1 level 1352:1356 O-GlcNAcylation level 1336:1356 O-GlcNAcylation level 1336:1356 Moreover, removal of O-GlcNAc from glycosylated CTD is also distributive and is independent of O-GlcNAcylation level. 28012591 6 0 theme tryptic 1060:1066 arg1 digest 1068:1073 standard tryptic digest 1051:1073 standard tryptic digest of human IgG 1051:1086 The detection sensitivity for glycopeptide determined by MALDI-TOF MS was as low as 5 fmol for standard tryptic digest of human IgG. 28012591 4 1 theme resulting 609:617 arg1 HA/CS 624:628 MAR@(HA/CS)20 619:631 The resulting MAR@(HA/CS)20 605:631 The resulting MAR@(HA/CS)20 possesses highly hydrophilic property and rapid adsorption behavior. 28012591 2 2 theme suspension 334:343 arg1 polymerization 345:358 suspension polymerization 334:358 suspension polymerization 334:358 Polydisperse MAR with approximately 250μm in diameter was synthesized via suspension polymerization and then modified with polysaccharides, sodium hyaluronate (HA) and chitosan (CS), through layer-by-layer (LbL) self-assembly process. 28012591 8 3 from enrichment 1435:1444 arg1 potential 1401:1409 the great potential 1391:1409 the great potential of MAR@(HA/CS)20 in the enrichment and identification of low-abundance N-linked glycopeptides in complicated biological samples 1391:1537 Furthermore, in the analysis of real biological sample, 745 unique N-glycosylation sites in 1353 unique glycopeptides mapped to 379 N-glycosylated proteins were identified in three replicate analyses of protein sample extracted from mouse liver, showing the great potential of MAR@(HA/CS)20 in the enrichment and identification of low-abundance N-linked glycopeptides in complicated biological samples. 28012591 8 3 from enrichment 1435:1444 arg1 samples 1531:1537 complicated biological samples 1508:1537 complicated biological samples 1508:1537 Furthermore, in the analysis of real biological sample, 745 unique N-glycosylation sites in 1353 unique glycopeptides mapped to 379 N-glycosylated proteins were identified in three replicate analyses of protein sample extracted from mouse liver, showing the great potential of MAR@(HA/CS)20 in the enrichment and identification of low-abundance N-linked glycopeptides in complicated biological samples. 28012591 1 4 theme resin 233:237 arg1 preparation 153:163 preparation 153:163 preparation of hydrophilic polysaccharide-functionalized macroporous adsorption resin (MAR) 153:243 A facile approach for preparation of hydrophilic polysaccharide-functionalized macroporous adsorption resin (MAR) was presented. 28012591 4 5 theme rapid 675:679 arg1 behavior 692:699 rapid adsorption behavior 675:699 rapid adsorption behavior 675:699 The resulting MAR@(HA/CS)20 possesses highly hydrophilic property and rapid adsorption behavior. 28012591 8 6 dep analyses 1328:1335 arg1 replicate 1318:1326 replicate 1318:1326 replicate 1318:1326 Furthermore, in the analysis of real biological sample, 745 unique N-glycosylation sites in 1353 unique glycopeptides mapped to 379 N-glycosylated proteins were identified in three replicate analyses of protein sample extracted from mouse liver, showing the great potential of MAR@(HA/CS)20 in the enrichment and identification of low-abundance N-linked glycopeptides in complicated biological samples. 28012591 2 7 with Polydisperse 260:271 arg1 250μm 296:300 250μm 296:300 250μm 296:300 Polydisperse MAR with approximately 250μm in diameter was synthesized via suspension polymerization and then modified with polysaccharides, sodium hyaluronate (HA) and chitosan (CS), through layer-by-layer (LbL) self-assembly process. 28012591 5 8 theme solid-phase 919:929 arg1 extraction 931:940 a homemade solid-phase extraction 908:940 a homemade solid-phase extraction (SPE) column 908:953 The specificity and efficiency of MAR@(HA/CS)20 to glycopeptide was demonstrated by trapping N-linked glycopeptide from tryptic digests of human immunoglobulin G (IgG) and horseradish peroxidase (HRP) with a homemade solid-phase extraction (SPE) column. 28012591 5 8 theme solid-phase 919:929 arg1 SPE 943:945 SPE 943:945 SPE 943:945 The specificity and efficiency of MAR@(HA/CS)20 to glycopeptide was demonstrated by trapping N-linked glycopeptide from tryptic digests of human immunoglobulin G (IgG) and horseradish peroxidase (HRP) with a homemade solid-phase extraction (SPE) column. 28012591 3 9 theme grams 582:586 arg1 tens 574:577 tens 574:577 tens of grams to one kilogram 574:602 The preparation method was facile, low cost and easy to expand production from tens of grams to one kilogram. 28012591 8 10 from identification 1450:1463 arg1 potential 1401:1409 the great potential 1391:1409 the great potential of MAR@(HA/CS)20 in the enrichment and identification of low-abundance N-linked glycopeptides in complicated biological samples 1391:1537 Furthermore, in the analysis of real biological sample, 745 unique N-glycosylation sites in 1353 unique glycopeptides mapped to 379 N-glycosylated proteins were identified in three replicate analyses of protein sample extracted from mouse liver, showing the great potential of MAR@(HA/CS)20 in the enrichment and identification of low-abundance N-linked glycopeptides in complicated biological samples. 28012591 8 10 from identification 1450:1463 arg1 samples 1531:1537 complicated biological samples 1508:1537 complicated biological samples 1508:1537 Furthermore, in the analysis of real biological sample, 745 unique N-glycosylation sites in 1353 unique glycopeptides mapped to 379 N-glycosylated proteins were identified in three replicate analyses of protein sample extracted from mouse liver, showing the great potential of MAR@(HA/CS)20 in the enrichment and identification of low-abundance N-linked glycopeptides in complicated biological samples. 28012591 5 11 theme immunoglobulin 847:860 arg1 IgG 865:867 IgG 865:867 IgG 865:867 The specificity and efficiency of MAR@(HA/CS)20 to glycopeptide was demonstrated by trapping N-linked glycopeptide from tryptic digests of human immunoglobulin G (IgG) and horseradish peroxidase (HRP) with a homemade solid-phase extraction (SPE) column. 28012591 5 11 theme immunoglobulin 847:860 arg1 G 862:862 human immunoglobulin G 841:862 human immunoglobulin G (IgG) 841:868 The specificity and efficiency of MAR@(HA/CS)20 to glycopeptide was demonstrated by trapping N-linked glycopeptide from tryptic digests of human immunoglobulin G (IgG) and horseradish peroxidase (HRP) with a homemade solid-phase extraction (SPE) column. 28012591 8 12 theme biological 1174:1183 arg1 sample 1185:1190 real biological sample 1169:1190 real biological sample 1169:1190 Furthermore, in the analysis of real biological sample, 745 unique N-glycosylation sites in 1353 unique glycopeptides mapped to 379 N-glycosylated proteins were identified in three replicate analyses of protein sample extracted from mouse liver, showing the great potential of MAR@(HA/CS)20 in the enrichment and identification of low-abundance N-linked glycopeptides in complicated biological samples. 28012591 8 13 theme MAR 1414:1416 arg1 HA/CS 1419:1423 MAR@(HA/CS)20 1414:1426 MAR@(HA/CS)20 in the enrichment and identification of low-abundance N-linked glycopeptides in complicated biological samples 1414:1537 Furthermore, in the analysis of real biological sample, 745 unique N-glycosylation sites in 1353 unique glycopeptides mapped to 379 N-glycosylated proteins were identified in three replicate analyses of protein sample extracted from mouse liver, showing the great potential of MAR@(HA/CS)20 in the enrichment and identification of low-abundance N-linked glycopeptides in complicated biological samples. 28012591 8 14 gly N-glycosylation 1204:1218 arg2 sites 1220:1224 745 unique N-glycosylation sites 1193:1224 745 unique N-glycosylation sites in 1353 unique glycopeptides mapped to 379 N-glycosylated proteins 1193:1291 Furthermore, in the analysis of real biological sample, 745 unique N-glycosylation sites in 1353 unique glycopeptides mapped to 379 N-glycosylated proteins were identified in three replicate analyses of protein sample extracted from mouse liver, showing the great potential of MAR@(HA/CS)20 in the enrichment and identification of low-abundance N-linked glycopeptides in complicated biological samples. 28012591 8 14 gly N-glycosylation 1204:1218 arg2 745 1193:1195 745 1193:1195 745 1193:1195 Furthermore, in the analysis of real biological sample, 745 unique N-glycosylation sites in 1353 unique glycopeptides mapped to 379 N-glycosylated proteins were identified in three replicate analyses of protein sample extracted from mouse liver, showing the great potential of MAR@(HA/CS)20 in the enrichment and identification of low-abundance N-linked glycopeptides in complicated biological samples. 28012591 5 15 from digests 830:836 arg1 glycopeptide 804:815 trapping N-linked glycopeptide 786:815 trapping N-linked glycopeptide from tryptic digests of human immunoglobulin G (IgG) and horseradish peroxidase (HRP) with a homemade solid-phase extraction (SPE) column 786:953 The specificity and efficiency of MAR@(HA/CS)20 to glycopeptide was demonstrated by trapping N-linked glycopeptide from tryptic digests of human immunoglobulin G (IgG) and horseradish peroxidase (HRP) with a homemade solid-phase extraction (SPE) column. 28012591 1 16 theme hydrophilic 168:178 arg1 MAR 240:242 MAR 240:242 MAR 240:242 A facile approach for preparation of hydrophilic polysaccharide-functionalized macroporous adsorption resin (MAR) was presented. 28012591 1 16 theme hydrophilic 168:178 arg1 resin 233:237 hydrophilic polysaccharide-functionalized macroporous adsorption resin 168:237 hydrophilic polysaccharide-functionalized macroporous adsorption resin (MAR) 168:243 A facile approach for preparation of hydrophilic polysaccharide-functionalized macroporous adsorption resin (MAR) was presented. 28012591 8 17 theme N-glycosylated 1269:1282 arg1 proteins 1284:1291 379 N-glycosylated proteins 1265:1291 379 N-glycosylated proteins 1265:1291 Furthermore, in the analysis of real biological sample, 745 unique N-glycosylation sites in 1353 unique glycopeptides mapped to 379 N-glycosylated proteins were identified in three replicate analyses of protein sample extracted from mouse liver, showing the great potential of MAR@(HA/CS)20 in the enrichment and identification of low-abundance N-linked glycopeptides in complicated biological samples. 28012591 8 18 from sites 1220:1224 arg1 glycopeptides 1241:1253 1353 unique glycopeptides 1229:1253 1353 unique glycopeptides mapped to 379 N-glycosylated proteins 1229:1291 Furthermore, in the analysis of real biological sample, 745 unique N-glycosylation sites in 1353 unique glycopeptides mapped to 379 N-glycosylated proteins were identified in three replicate analyses of protein sample extracted from mouse liver, showing the great potential of MAR@(HA/CS)20 in the enrichment and identification of low-abundance N-linked glycopeptides in complicated biological samples. 28012591 5 19 theme horseradish 874:884 arg1 peroxidase 886:895 horseradish peroxidase 874:895 horseradish peroxidase (HRP) 874:901 The specificity and efficiency of MAR@(HA/CS)20 to glycopeptide was demonstrated by trapping N-linked glycopeptide from tryptic digests of human immunoglobulin G (IgG) and horseradish peroxidase (HRP) with a homemade solid-phase extraction (SPE) column. 28012591 5 19 theme horseradish 874:884 arg1 HRP 898:900 HRP 898:900 HRP 898:900 The specificity and efficiency of MAR@(HA/CS)20 to glycopeptide was demonstrated by trapping N-linked glycopeptide from tryptic digests of human immunoglobulin G (IgG) and horseradish peroxidase (HRP) with a homemade solid-phase extraction (SPE) column. 28012591 5 20 dep specificity 706:716 arg1 The 702:704 The 702:704 The 702:704 The specificity and efficiency of MAR@(HA/CS)20 to glycopeptide was demonstrated by trapping N-linked glycopeptide from tryptic digests of human immunoglobulin G (IgG) and horseradish peroxidase (HRP) with a homemade solid-phase extraction (SPE) column. 28012591 0 21 theme selective 92:100 arg1 enrichment 102:111 highly selective enrichment 85:111 highly selective enrichment of glycopeptides 85:128 Facile preparation of polysaccharide functionalized macroporous adsorption resin for highly selective enrichment of glycopeptides. 28012591 1 22 theme macroporous 210:220 arg1 MAR 240:242 MAR 240:242 MAR 240:242 A facile approach for preparation of hydrophilic polysaccharide-functionalized macroporous adsorption resin (MAR) was presented. 28012591 1 22 theme macroporous 210:220 arg1 resin 233:237 hydrophilic polysaccharide-functionalized macroporous adsorption resin 168:237 hydrophilic polysaccharide-functionalized macroporous adsorption resin (MAR) 168:243 A facile approach for preparation of hydrophilic polysaccharide-functionalized macroporous adsorption resin (MAR) was presented. 28012591 3 23 from tens 574:577 arg1 production 558:567 production 558:567 production from tens of grams to one kilogram 558:602 The preparation method was facile, low cost and easy to expand production from tens of grams to one kilogram. 28012591 5 24 theme @ 739:739 arg1 HA/CS 741:745 MAR@(HA/CS)20 736:748 MAR@(HA/CS)20 736:748 The specificity and efficiency of MAR@(HA/CS)20 to glycopeptide was demonstrated by trapping N-linked glycopeptide from tryptic digests of human immunoglobulin G (IgG) and horseradish peroxidase (HRP) with a homemade solid-phase extraction (SPE) column. 28012591 5 25 gly glycopeptide 753:764 arg2 glycopeptide 753:764 glycopeptide 753:764 glycopeptide 753:764 The specificity and efficiency of MAR@(HA/CS)20 to glycopeptide was demonstrated by trapping N-linked glycopeptide from tryptic digests of human immunoglobulin G (IgG) and horseradish peroxidase (HRP) with a homemade solid-phase extraction (SPE) column. 28012591 5 26 theme HA/CS 741:745 arg1 efficiency 722:731 efficiency 722:731 efficiency 722:731 The specificity and efficiency of MAR@(HA/CS)20 to glycopeptide was demonstrated by trapping N-linked glycopeptide from tryptic digests of human immunoglobulin G (IgG) and horseradish peroxidase (HRP) with a homemade solid-phase extraction (SPE) column. 28012591 5 26 theme HA/CS 741:745 arg1 specificity 706:716 specificity 706:716 specificity 706:716 The specificity and efficiency of MAR@(HA/CS)20 to glycopeptide was demonstrated by trapping N-linked glycopeptide from tryptic digests of human immunoglobulin G (IgG) and horseradish peroxidase (HRP) with a homemade solid-phase extraction (SPE) column. 28012591 8 27 theme low-abundance 1468:1480 arg1 glycopeptides 1491:1503 low-abundance N-linked glycopeptides 1468:1503 low-abundance N-linked glycopeptides 1468:1503 Furthermore, in the analysis of real biological sample, 745 unique N-glycosylation sites in 1353 unique glycopeptides mapped to 379 N-glycosylated proteins were identified in three replicate analyses of protein sample extracted from mouse liver, showing the great potential of MAR@(HA/CS)20 in the enrichment and identification of low-abundance N-linked glycopeptides in complicated biological samples. 28012591 0 28 theme Facile 0:5 arg1 preparation 7:17 Facile preparation 0:17 Facile preparation of polysaccharide 0:35 Facile preparation of polysaccharide functionalized macroporous adsorption resin for highly selective enrichment of glycopeptides. 28012591 2 29 mod modified 369:376 arg3 polysaccharides 383:397 polysaccharides 383:397 polysaccharides 383:397 Polydisperse MAR with approximately 250μm in diameter was synthesized via suspension polymerization and then modified with polysaccharides, sodium hyaluronate (HA) and chitosan (CS), through layer-by-layer (LbL) self-assembly process. 28012591 2 29 mod modified 369:376 arg1 Polydisperse 260:271 Polydisperse MAR 260:275 Polydisperse MAR with approximately 250μm in diameter 260:312 Polydisperse MAR with approximately 250μm in diameter was synthesized via suspension polymerization and then modified with polysaccharides, sodium hyaluronate (HA) and chitosan (CS), through layer-by-layer (LbL) self-assembly process. 28012591 2 29 mod modified 369:376 arg3 CS 438:439 CS 438:439 CS 438:439 Polydisperse MAR with approximately 250μm in diameter was synthesized via suspension polymerization and then modified with polysaccharides, sodium hyaluronate (HA) and chitosan (CS), through layer-by-layer (LbL) self-assembly process. 28012591 2 29 mod modified 369:376 arg3 HA 420:421 HA 420:421 HA 420:421 Polydisperse MAR with approximately 250μm in diameter was synthesized via suspension polymerization and then modified with polysaccharides, sodium hyaluronate (HA) and chitosan (CS), through layer-by-layer (LbL) self-assembly process. 28012591 2 29 mod modified 369:376 arg3 chitosan 428:435 chitosan 428:435 chitosan (CS) 428:440 Polydisperse MAR with approximately 250μm in diameter was synthesized via suspension polymerization and then modified with polysaccharides, sodium hyaluronate (HA) and chitosan (CS), through layer-by-layer (LbL) self-assembly process. 28012591 2 29 mod modified 369:376 arg3 hyaluronate 407:417 sodium hyaluronate 400:417 sodium hyaluronate (HA) 400:422 Polydisperse MAR with approximately 250μm in diameter was synthesized via suspension polymerization and then modified with polysaccharides, sodium hyaluronate (HA) and chitosan (CS), through layer-by-layer (LbL) self-assembly process. 28012591 0 30 gly glycopeptides 116:128 arg2 glycopeptides 116:128 glycopeptides 116:128 glycopeptides 116:128 Facile preparation of polysaccharide functionalized macroporous adsorption resin for highly selective enrichment of glycopeptides. 28012591 8 31 theme glycopeptides 1491:1503 arg1 enrichment 1435:1444 the enrichment 1431:1444 the enrichment 1431:1444 Furthermore, in the analysis of real biological sample, 745 unique N-glycosylation sites in 1353 unique glycopeptides mapped to 379 N-glycosylated proteins were identified in three replicate analyses of protein sample extracted from mouse liver, showing the great potential of MAR@(HA/CS)20 in the enrichment and identification of low-abundance N-linked glycopeptides in complicated biological samples. 28012591 8 31 theme glycopeptides 1491:1503 arg1 identification 1450:1463 identification 1450:1463 identification 1450:1463 Furthermore, in the analysis of real biological sample, 745 unique N-glycosylation sites in 1353 unique glycopeptides mapped to 379 N-glycosylated proteins were identified in three replicate analyses of protein sample extracted from mouse liver, showing the great potential of MAR@(HA/CS)20 in the enrichment and identification of low-abundance N-linked glycopeptides in complicated biological samples. 28012591 8 32 theme sample 1348:1353 arg1 analyses 1328:1335 three replicate analyses 1312:1335 three replicate analyses of protein sample extracted from mouse liver 1312:1380 Furthermore, in the analysis of real biological sample, 745 unique N-glycosylation sites in 1353 unique glycopeptides mapped to 379 N-glycosylated proteins were identified in three replicate analyses of protein sample extracted from mouse liver, showing the great potential of MAR@(HA/CS)20 in the enrichment and identification of low-abundance N-linked glycopeptides in complicated biological samples. 28012591 3 33 theme preparation 499:509 arg1 facile 522:527 facile 522:527 facile 522:527 The preparation method was facile, low cost and easy to expand production from tens of grams to one kilogram. 28012591 3 33 theme preparation 499:509 arg1 method 511:516 The preparation method 495:516 The preparation method 495:516 The preparation method was facile, low cost and easy to expand production from tens of grams to one kilogram. 28012591 5 34 theme tryptic 822:828 arg1 digests 830:836 tryptic digests 822:836 tryptic digests of human immunoglobulin G (IgG) and horseradish peroxidase (HRP) with a homemade solid-phase extraction (SPE) column 822:953 The specificity and efficiency of MAR@(HA/CS)20 to glycopeptide was demonstrated by trapping N-linked glycopeptide from tryptic digests of human immunoglobulin G (IgG) and horseradish peroxidase (HRP) with a homemade solid-phase extraction (SPE) column. 28012591 8 35 theme complicated 1508:1518 arg1 samples 1531:1537 complicated biological samples 1508:1537 complicated biological samples 1508:1537 Furthermore, in the analysis of real biological sample, 745 unique N-glycosylation sites in 1353 unique glycopeptides mapped to 379 N-glycosylated proteins were identified in three replicate analyses of protein sample extracted from mouse liver, showing the great potential of MAR@(HA/CS)20 in the enrichment and identification of low-abundance N-linked glycopeptides in complicated biological samples. 28012591 5 36 with digests 830:836 arg1 column 948:953 a homemade solid-phase extraction (SPE) column 908:953 a homemade solid-phase extraction (SPE) column 908:953 The specificity and efficiency of MAR@(HA/CS)20 to glycopeptide was demonstrated by trapping N-linked glycopeptide from tryptic digests of human immunoglobulin G (IgG) and horseradish peroxidase (HRP) with a homemade solid-phase extraction (SPE) column. 28012591 5 37 gly glycopeptide 804:815 arg2 glycopeptide 804:815 trapping N-linked glycopeptide 786:815 trapping N-linked glycopeptide from tryptic digests of human immunoglobulin G (IgG) and horseradish peroxidase (HRP) with a homemade solid-phase extraction (SPE) column 786:953 The specificity and efficiency of MAR@(HA/CS)20 to glycopeptide was demonstrated by trapping N-linked glycopeptide from tryptic digests of human immunoglobulin G (IgG) and horseradish peroxidase (HRP) with a homemade solid-phase extraction (SPE) column. 28012591 5 37 gly glycopeptide 804:815 arg1 digests 830:836 tryptic digests 822:836 tryptic digests of human immunoglobulin G (IgG) and horseradish peroxidase (HRP) with a homemade solid-phase extraction (SPE) column 822:953 The specificity and efficiency of MAR@(HA/CS)20 to glycopeptide was demonstrated by trapping N-linked glycopeptide from tryptic digests of human immunoglobulin G (IgG) and horseradish peroxidase (HRP) with a homemade solid-phase extraction (SPE) column. 28012591 5 38 theme G 862:862 arg1 digests 830:836 tryptic digests 822:836 tryptic digests of human immunoglobulin G (IgG) and horseradish peroxidase (HRP) with a homemade solid-phase extraction (SPE) column 822:953 The specificity and efficiency of MAR@(HA/CS)20 to glycopeptide was demonstrated by trapping N-linked glycopeptide from tryptic digests of human immunoglobulin G (IgG) and horseradish peroxidase (HRP) with a homemade solid-phase extraction (SPE) column. 28012591 5 39 theme trapping 786:793 arg1 glycopeptide 804:815 trapping N-linked glycopeptide 786:815 trapping N-linked glycopeptide from tryptic digests of human immunoglobulin G (IgG) and horseradish peroxidase (HRP) with a homemade solid-phase extraction (SPE) column 786:953 The specificity and efficiency of MAR@(HA/CS)20 to glycopeptide was demonstrated by trapping N-linked glycopeptide from tryptic digests of human immunoglobulin G (IgG) and horseradish peroxidase (HRP) with a homemade solid-phase extraction (SPE) column. 28012591 6 40 theme human 1078:1082 arg1 IgG 1084:1086 human IgG 1078:1086 human IgG 1078:1086 The detection sensitivity for glycopeptide determined by MALDI-TOF MS was as low as 5 fmol for standard tryptic digest of human IgG. 28012591 4 41 theme MAR 619:621 arg1 HA/CS 624:628 MAR@(HA/CS)20 619:631 The resulting MAR@(HA/CS)20 605:631 The resulting MAR@(HA/CS)20 possesses highly hydrophilic property and rapid adsorption behavior. 28012591 8 42 theme great 1395:1399 arg1 potential 1401:1409 the great potential 1391:1409 the great potential of MAR@(HA/CS)20 in the enrichment and identification of low-abundance N-linked glycopeptides in complicated biological samples 1391:1537 Furthermore, in the analysis of real biological sample, 745 unique N-glycosylation sites in 1353 unique glycopeptides mapped to 379 N-glycosylated proteins were identified in three replicate analyses of protein sample extracted from mouse liver, showing the great potential of MAR@(HA/CS)20 in the enrichment and identification of low-abundance N-linked glycopeptides in complicated biological samples. 28012591 4 43 theme hydrophilic 650:660 arg1 property 662:669 highly hydrophilic property 643:669 highly hydrophilic property 643:669 The resulting MAR@(HA/CS)20 possesses highly hydrophilic property and rapid adsorption behavior. 28012591 6 44 theme standard 1051:1058 arg1 digest 1068:1073 standard tryptic digest 1051:1073 standard tryptic digest of human IgG 1051:1086 The detection sensitivity for glycopeptide determined by MALDI-TOF MS was as low as 5 fmol for standard tryptic digest of human IgG. 28012591 5 45 theme peroxidase 886:895 arg1 digests 830:836 tryptic digests 822:836 tryptic digests of human immunoglobulin G (IgG) and horseradish peroxidase (HRP) with a homemade solid-phase extraction (SPE) column 822:953 The specificity and efficiency of MAR@(HA/CS)20 to glycopeptide was demonstrated by trapping N-linked glycopeptide from tryptic digests of human immunoglobulin G (IgG) and horseradish peroxidase (HRP) with a homemade solid-phase extraction (SPE) column. 28012591 8 46 theme unique 1197:1202 arg1 sites 1220:1224 745 unique N-glycosylation sites 1193:1224 745 unique N-glycosylation sites in 1353 unique glycopeptides mapped to 379 N-glycosylated proteins 1193:1291 Furthermore, in the analysis of real biological sample, 745 unique N-glycosylation sites in 1353 unique glycopeptides mapped to 379 N-glycosylated proteins were identified in three replicate analyses of protein sample extracted from mouse liver, showing the great potential of MAR@(HA/CS)20 in the enrichment and identification of low-abundance N-linked glycopeptides in complicated biological samples. 28012591 1 47 theme adsorption 222:231 arg1 MAR 240:242 MAR 240:242 MAR 240:242 A facile approach for preparation of hydrophilic polysaccharide-functionalized macroporous adsorption resin (MAR) was presented. 28012591 1 47 theme adsorption 222:231 arg1 resin 233:237 hydrophilic polysaccharide-functionalized macroporous adsorption resin 168:237 hydrophilic polysaccharide-functionalized macroporous adsorption resin (MAR) 168:243 A facile approach for preparation of hydrophilic polysaccharide-functionalized macroporous adsorption resin (MAR) was presented. 28012591 0 48 theme adsorption 64:73 arg1 resin 75:79 macroporous adsorption resin 52:79 macroporous adsorption resin for highly selective enrichment of glycopeptides 52:128 Facile preparation of polysaccharide functionalized macroporous adsorption resin for highly selective enrichment of glycopeptides. 28012591 8 49 theme sample 1185:1190 arg1 analysis 1157:1164 the analysis 1153:1164 the analysis of real biological sample 1153:1190 Furthermore, in the analysis of real biological sample, 745 unique N-glycosylation sites in 1353 unique glycopeptides mapped to 379 N-glycosylated proteins were identified in three replicate analyses of protein sample extracted from mouse liver, showing the great potential of MAR@(HA/CS)20 in the enrichment and identification of low-abundance N-linked glycopeptides in complicated biological samples. 28012591 8 50 from potential 1401:1409 arg1 enrichment 1435:1444 the enrichment 1431:1444 the enrichment 1431:1444 Furthermore, in the analysis of real biological sample, 745 unique N-glycosylation sites in 1353 unique glycopeptides mapped to 379 N-glycosylated proteins were identified in three replicate analyses of protein sample extracted from mouse liver, showing the great potential of MAR@(HA/CS)20 in the enrichment and identification of low-abundance N-linked glycopeptides in complicated biological samples. 28012591 8 50 from potential 1401:1409 arg1 identification 1450:1463 identification 1450:1463 identification 1450:1463 Furthermore, in the analysis of real biological sample, 745 unique N-glycosylation sites in 1353 unique glycopeptides mapped to 379 N-glycosylated proteins were identified in three replicate analyses of protein sample extracted from mouse liver, showing the great potential of MAR@(HA/CS)20 in the enrichment and identification of low-abundance N-linked glycopeptides in complicated biological samples. 28012591 2 51 dep Polydisperse 260:271 arg1 MAR 273:275 MAR 273:275 MAR 273:275 Polydisperse MAR with approximately 250μm in diameter was synthesized via suspension polymerization and then modified with polysaccharides, sodium hyaluronate (HA) and chitosan (CS), through layer-by-layer (LbL) self-assembly process. 28012591 5 52 theme human 841:845 arg1 IgG 865:867 IgG 865:867 IgG 865:867 The specificity and efficiency of MAR@(HA/CS)20 to glycopeptide was demonstrated by trapping N-linked glycopeptide from tryptic digests of human immunoglobulin G (IgG) and horseradish peroxidase (HRP) with a homemade solid-phase extraction (SPE) column. 28012591 5 52 theme human 841:845 arg1 G 862:862 human immunoglobulin G 841:862 human immunoglobulin G (IgG) 841:868 The specificity and efficiency of MAR@(HA/CS)20 to glycopeptide was demonstrated by trapping N-linked glycopeptide from tryptic digests of human immunoglobulin G (IgG) and horseradish peroxidase (HRP) with a homemade solid-phase extraction (SPE) column. 28012591 8 53 theme @ 1417:1417 arg1 HA/CS 1419:1423 MAR@(HA/CS)20 1414:1426 MAR@(HA/CS)20 in the enrichment and identification of low-abundance N-linked glycopeptides in complicated biological samples 1414:1537 Furthermore, in the analysis of real biological sample, 745 unique N-glycosylation sites in 1353 unique glycopeptides mapped to 379 N-glycosylated proteins were identified in three replicate analyses of protein sample extracted from mouse liver, showing the great potential of MAR@(HA/CS)20 in the enrichment and identification of low-abundance N-linked glycopeptides in complicated biological samples. 28012591 5 54 theme MAR 736:738 arg1 HA/CS 741:745 MAR@(HA/CS)20 736:748 MAR@(HA/CS)20 736:748 The specificity and efficiency of MAR@(HA/CS)20 to glycopeptide was demonstrated by trapping N-linked glycopeptide from tryptic digests of human immunoglobulin G (IgG) and horseradish peroxidase (HRP) with a homemade solid-phase extraction (SPE) column. 28012591 1 55 theme facile 133:138 arg1 approach 140:147 A facile approach 131:147 A facile approach for preparation of hydrophilic polysaccharide-functionalized macroporous adsorption resin (MAR) 131:243 A facile approach for preparation of hydrophilic polysaccharide-functionalized macroporous adsorption resin (MAR) was presented. 28012591 8 56 theme real 1169:1172 arg1 sample 1185:1190 real biological sample 1169:1190 real biological sample 1169:1190 Furthermore, in the analysis of real biological sample, 745 unique N-glycosylation sites in 1353 unique glycopeptides mapped to 379 N-glycosylated proteins were identified in three replicate analyses of protein sample extracted from mouse liver, showing the great potential of MAR@(HA/CS)20 in the enrichment and identification of low-abundance N-linked glycopeptides in complicated biological samples. 28012591 8 57 theme HA/CS 1419:1423 arg1 potential 1401:1409 the great potential 1391:1409 the great potential of MAR@(HA/CS)20 in the enrichment and identification of low-abundance N-linked glycopeptides in complicated biological samples 1391:1537 Furthermore, in the analysis of real biological sample, 745 unique N-glycosylation sites in 1353 unique glycopeptides mapped to 379 N-glycosylated proteins were identified in three replicate analyses of protein sample extracted from mouse liver, showing the great potential of MAR@(HA/CS)20 in the enrichment and identification of low-abundance N-linked glycopeptides in complicated biological samples. 28012591 8 58 theme unique 1234:1239 arg1 glycopeptides 1241:1253 1353 unique glycopeptides 1229:1253 1353 unique glycopeptides mapped to 379 N-glycosylated proteins 1229:1291 Furthermore, in the analysis of real biological sample, 745 unique N-glycosylation sites in 1353 unique glycopeptides mapped to 379 N-glycosylated proteins were identified in three replicate analyses of protein sample extracted from mouse liver, showing the great potential of MAR@(HA/CS)20 in the enrichment and identification of low-abundance N-linked glycopeptides in complicated biological samples. 28012591 6 59 theme MALDI-TOF 1013:1021 arg1 MS 1023:1024 MALDI-TOF MS 1013:1024 MALDI-TOF MS 1013:1024 The detection sensitivity for glycopeptide determined by MALDI-TOF MS was as low as 5 fmol for standard tryptic digest of human IgG. 28012591 5 60 link N-linked 795:802 arg1 glycopeptide 804:815 trapping N-linked glycopeptide 786:815 trapping N-linked glycopeptide from tryptic digests of human immunoglobulin G (IgG) and horseradish peroxidase (HRP) with a homemade solid-phase extraction (SPE) column 786:953 The specificity and efficiency of MAR@(HA/CS)20 to glycopeptide was demonstrated by trapping N-linked glycopeptide from tryptic digests of human immunoglobulin G (IgG) and horseradish peroxidase (HRP) with a homemade solid-phase extraction (SPE) column. 28012591 4 61 theme adsorption 681:690 arg1 behavior 692:699 rapid adsorption behavior 675:699 rapid adsorption behavior 675:699 The resulting MAR@(HA/CS)20 possesses highly hydrophilic property and rapid adsorption behavior. 28012591 8 62 gly glycopeptides 1241:1253 arg2 glycopeptides 1241:1253 1353 unique glycopeptides 1229:1253 1353 unique glycopeptides mapped to 379 N-glycosylated proteins 1229:1291 Furthermore, in the analysis of real biological sample, 745 unique N-glycosylation sites in 1353 unique glycopeptides mapped to 379 N-glycosylated proteins were identified in three replicate analyses of protein sample extracted from mouse liver, showing the great potential of MAR@(HA/CS)20 in the enrichment and identification of low-abundance N-linked glycopeptides in complicated biological samples. 28012591 1 63 theme polysaccharide-functionalized 180:208 arg1 MAR 240:242 MAR 240:242 MAR 240:242 A facile approach for preparation of hydrophilic polysaccharide-functionalized macroporous adsorption resin (MAR) was presented. 28012591 1 63 theme polysaccharide-functionalized 180:208 arg1 resin 233:237 hydrophilic polysaccharide-functionalized macroporous adsorption resin 168:237 hydrophilic polysaccharide-functionalized macroporous adsorption resin (MAR) 168:243 A facile approach for preparation of hydrophilic polysaccharide-functionalized macroporous adsorption resin (MAR) was presented. 28012591 0 64 theme glycopeptides 116:128 arg1 enrichment 102:111 highly selective enrichment 85:111 highly selective enrichment of glycopeptides 85:128 Facile preparation of polysaccharide functionalized macroporous adsorption resin for highly selective enrichment of glycopeptides. 28012591 8 65 gly glycopeptides 1491:1503 arg2 glycopeptides 1491:1503 low-abundance N-linked glycopeptides 1468:1503 low-abundance N-linked glycopeptides 1468:1503 Furthermore, in the analysis of real biological sample, 745 unique N-glycosylation sites in 1353 unique glycopeptides mapped to 379 N-glycosylated proteins were identified in three replicate analyses of protein sample extracted from mouse liver, showing the great potential of MAR@(HA/CS)20 in the enrichment and identification of low-abundance N-linked glycopeptides in complicated biological samples. 28012591 6 66 theme detection 960:968 arg1 sensitivity 970:980 The detection sensitivity 956:980 The detection sensitivity for glycopeptide determined by MALDI-TOF MS 956:1024 The detection sensitivity for glycopeptide determined by MALDI-TOF MS was as low as 5 fmol for standard tryptic digest of human IgG. 28012591 6 66 theme detection 960:968 arg1 low 1033:1035 low 1033:1035 low 1033:1035 The detection sensitivity for glycopeptide determined by MALDI-TOF MS was as low as 5 fmol for standard tryptic digest of human IgG. 28012591 8 67 from HA/CS 1419:1423 arg1 enrichment 1435:1444 the enrichment 1431:1444 the enrichment 1431:1444 Furthermore, in the analysis of real biological sample, 745 unique N-glycosylation sites in 1353 unique glycopeptides mapped to 379 N-glycosylated proteins were identified in three replicate analyses of protein sample extracted from mouse liver, showing the great potential of MAR@(HA/CS)20 in the enrichment and identification of low-abundance N-linked glycopeptides in complicated biological samples. 28012591 8 67 from HA/CS 1419:1423 arg1 identification 1450:1463 identification 1450:1463 identification 1450:1463 Furthermore, in the analysis of real biological sample, 745 unique N-glycosylation sites in 1353 unique glycopeptides mapped to 379 N-glycosylated proteins were identified in three replicate analyses of protein sample extracted from mouse liver, showing the great potential of MAR@(HA/CS)20 in the enrichment and identification of low-abundance N-linked glycopeptides in complicated biological samples. 28012591 8 68 gly N-glycosylated 1269:1282 arg1 proteins 1284:1291 379 N-glycosylated proteins 1265:1291 379 N-glycosylated proteins 1265:1291 Furthermore, in the analysis of real biological sample, 745 unique N-glycosylation sites in 1353 unique glycopeptides mapped to 379 N-glycosylated proteins were identified in three replicate analyses of protein sample extracted from mouse liver, showing the great potential of MAR@(HA/CS)20 in the enrichment and identification of low-abundance N-linked glycopeptides in complicated biological samples. 28012591 8 69 theme N-glycosylation 1204:1218 arg1 sites 1220:1224 745 unique N-glycosylation sites 1193:1224 745 unique N-glycosylation sites in 1353 unique glycopeptides mapped to 379 N-glycosylated proteins 1193:1291 Furthermore, in the analysis of real biological sample, 745 unique N-glycosylation sites in 1353 unique glycopeptides mapped to 379 N-glycosylated proteins were identified in three replicate analyses of protein sample extracted from mouse liver, showing the great potential of MAR@(HA/CS)20 in the enrichment and identification of low-abundance N-linked glycopeptides in complicated biological samples. 28012591 2 70 from Polydisperse 260:271 arg1 diameter 305:312 diameter 305:312 diameter 305:312 Polydisperse MAR with approximately 250μm in diameter was synthesized via suspension polymerization and then modified with polysaccharides, sodium hyaluronate (HA) and chitosan (CS), through layer-by-layer (LbL) self-assembly process. 28012591 8 71 theme N-linked 1482:1489 arg1 glycopeptides 1491:1503 low-abundance N-linked glycopeptides 1468:1503 low-abundance N-linked glycopeptides 1468:1503 Furthermore, in the analysis of real biological sample, 745 unique N-glycosylation sites in 1353 unique glycopeptides mapped to 379 N-glycosylated proteins were identified in three replicate analyses of protein sample extracted from mouse liver, showing the great potential of MAR@(HA/CS)20 in the enrichment and identification of low-abundance N-linked glycopeptides in complicated biological samples. 28012591 5 72 theme N-linked 795:802 arg1 glycopeptide 804:815 trapping N-linked glycopeptide 786:815 trapping N-linked glycopeptide from tryptic digests of human immunoglobulin G (IgG) and horseradish peroxidase (HRP) with a homemade solid-phase extraction (SPE) column 786:953 The specificity and efficiency of MAR@(HA/CS)20 to glycopeptide was demonstrated by trapping N-linked glycopeptide from tryptic digests of human immunoglobulin G (IgG) and horseradish peroxidase (HRP) with a homemade solid-phase extraction (SPE) column. 28012591 5 73 theme homemade 910:917 arg1 extraction 931:940 a homemade solid-phase extraction 908:940 a homemade solid-phase extraction (SPE) column 908:953 The specificity and efficiency of MAR@(HA/CS)20 to glycopeptide was demonstrated by trapping N-linked glycopeptide from tryptic digests of human immunoglobulin G (IgG) and horseradish peroxidase (HRP) with a homemade solid-phase extraction (SPE) column. 28012591 5 73 theme homemade 910:917 arg1 SPE 943:945 SPE 943:945 SPE 943:945 The specificity and efficiency of MAR@(HA/CS)20 to glycopeptide was demonstrated by trapping N-linked glycopeptide from tryptic digests of human immunoglobulin G (IgG) and horseradish peroxidase (HRP) with a homemade solid-phase extraction (SPE) column. 28012591 2 74 theme self-assembly 472:484 arg1 process 486:492 layer-by-layer (LbL) self-assembly process 451:492 layer-by-layer (LbL) self-assembly process 451:492 Polydisperse MAR with approximately 250μm in diameter was synthesized via suspension polymerization and then modified with polysaccharides, sodium hyaluronate (HA) and chitosan (CS), through layer-by-layer (LbL) self-assembly process. 28012591 0 75 theme polysaccharide 22:35 arg1 preparation 7:17 Facile preparation 0:17 Facile preparation of polysaccharide 0:35 Facile preparation of polysaccharide functionalized macroporous adsorption resin for highly selective enrichment of glycopeptides. 28012591 5 76 theme extraction 931:940 arg1 column 948:953 a homemade solid-phase extraction (SPE) column 908:953 a homemade solid-phase extraction (SPE) column 908:953 The specificity and efficiency of MAR@(HA/CS)20 to glycopeptide was demonstrated by trapping N-linked glycopeptide from tryptic digests of human immunoglobulin G (IgG) and horseradish peroxidase (HRP) with a homemade solid-phase extraction (SPE) column. 28012591 2 77 theme LbL 467:469 arg1 process 486:492 layer-by-layer (LbL) self-assembly process 451:492 layer-by-layer (LbL) self-assembly process 451:492 Polydisperse MAR with approximately 250μm in diameter was synthesized via suspension polymerization and then modified with polysaccharides, sodium hyaluronate (HA) and chitosan (CS), through layer-by-layer (LbL) self-assembly process. 28012591 8 78 theme biological 1520:1529 arg1 samples 1531:1537 complicated biological samples 1508:1537 complicated biological samples 1508:1537 Furthermore, in the analysis of real biological sample, 745 unique N-glycosylation sites in 1353 unique glycopeptides mapped to 379 N-glycosylated proteins were identified in three replicate analyses of protein sample extracted from mouse liver, showing the great potential of MAR@(HA/CS)20 in the enrichment and identification of low-abundance N-linked glycopeptides in complicated biological samples. 28012591 4 79 contain possesses 633:641 arg2 property 662:669 highly hydrophilic property 643:669 highly hydrophilic property 643:669 The resulting MAR@(HA/CS)20 possesses highly hydrophilic property and rapid adsorption behavior. 28012591 4 79 contain possesses 633:641 arg2 behavior 692:699 rapid adsorption behavior 675:699 rapid adsorption behavior 675:699 The resulting MAR@(HA/CS)20 possesses highly hydrophilic property and rapid adsorption behavior. 28012591 4 79 contain possesses 633:641 arg1 HA/CS 624:628 MAR@(HA/CS)20 619:631 The resulting MAR@(HA/CS)20 605:631 The resulting MAR@(HA/CS)20 possesses highly hydrophilic property and rapid adsorption behavior. 28012591 8 80 theme protein 1340:1346 arg1 sample 1348:1353 protein sample 1340:1353 protein sample extracted from mouse liver 1340:1380 Furthermore, in the analysis of real biological sample, 745 unique N-glycosylation sites in 1353 unique glycopeptides mapped to 379 N-glycosylated proteins were identified in three replicate analyses of protein sample extracted from mouse liver, showing the great potential of MAR@(HA/CS)20 in the enrichment and identification of low-abundance N-linked glycopeptides in complicated biological samples. 28012591 2 81 theme layer-by-layer 451:464 arg1 process 486:492 layer-by-layer (LbL) self-assembly process 451:492 layer-by-layer (LbL) self-assembly process 451:492 Polydisperse MAR with approximately 250μm in diameter was synthesized via suspension polymerization and then modified with polysaccharides, sodium hyaluronate (HA) and chitosan (CS), through layer-by-layer (LbL) self-assembly process. 28012591 0 82 theme macroporous 52:62 arg1 resin 75:79 macroporous adsorption resin 52:79 macroporous adsorption resin for highly selective enrichment of glycopeptides 52:128 Facile preparation of polysaccharide functionalized macroporous adsorption resin for highly selective enrichment of glycopeptides. 28012591 7 83 theme enrichment 1093:1102 arg1 higher 1120:1125 higher 1120:1125 higher 1120:1125 The enrichment recoveries were higher than 73%. 28012591 7 83 theme enrichment 1093:1102 arg1 recoveries 1104:1113 The enrichment recoveries 1089:1113 The enrichment recoveries 1089:1113 The enrichment recoveries were higher than 73%. 28012591 8 84 theme mouse 1370:1374 arg1 liver 1376:1380 mouse liver 1370:1380 mouse liver 1370:1380 Furthermore, in the analysis of real biological sample, 745 unique N-glycosylation sites in 1353 unique glycopeptides mapped to 379 N-glycosylated proteins were identified in three replicate analyses of protein sample extracted from mouse liver, showing the great potential of MAR@(HA/CS)20 in the enrichment and identification of low-abundance N-linked glycopeptides in complicated biological samples. 28012591 2 85 theme sodium 400:405 arg1 HA 420:421 HA 420:421 HA 420:421 Polydisperse MAR with approximately 250μm in diameter was synthesized via suspension polymerization and then modified with polysaccharides, sodium hyaluronate (HA) and chitosan (CS), through layer-by-layer (LbL) self-assembly process. 28012591 2 85 theme sodium 400:405 arg1 hyaluronate 407:417 sodium hyaluronate 400:417 sodium hyaluronate (HA) 400:422 Polydisperse MAR with approximately 250μm in diameter was synthesized via suspension polymerization and then modified with polysaccharides, sodium hyaluronate (HA) and chitosan (CS), through layer-by-layer (LbL) self-assembly process. 28012591 6 86 theme IgG 1084:1086 arg1 digest 1068:1073 standard tryptic digest 1051:1073 standard tryptic digest of human IgG 1051:1086 The detection sensitivity for glycopeptide determined by MALDI-TOF MS was as low as 5 fmol for standard tryptic digest of human IgG. 28012591 4 87 theme @ 622:622 arg1 HA/CS 624:628 MAR@(HA/CS)20 619:631 The resulting MAR@(HA/CS)20 605:631 The resulting MAR@(HA/CS)20 possesses highly hydrophilic property and rapid adsorption behavior. 28012591 8 88 link N-linked 1482:1489 arg1 glycopeptides 1491:1503 low-abundance N-linked glycopeptides 1468:1503 low-abundance N-linked glycopeptides 1468:1503 Furthermore, in the analysis of real biological sample, 745 unique N-glycosylation sites in 1353 unique glycopeptides mapped to 379 N-glycosylated proteins were identified in three replicate analyses of protein sample extracted from mouse liver, showing the great potential of MAR@(HA/CS)20 in the enrichment and identification of low-abundance N-linked glycopeptides in complicated biological samples. 28012591 6 89 gly glycopeptide 986:997 arg2 glycopeptide 986:997 glycopeptide 986:997 glycopeptide 986:997 The detection sensitivity for glycopeptide determined by MALDI-TOF MS was as low as 5 fmol for standard tryptic digest of human IgG. 29242193 7 0 theme nanomolar 1051:1059 arg1 affinity 1069:1076 a very tight nanomolar binding affinity 1038:1076 a very tight nanomolar binding affinity to m4-1BBL 1038:1087 Kinetics studies of m4-1BB disclosed a very tight nanomolar binding affinity to m4-1BBL with an unexpectedly strong avidity effect. 29242193 3 1 theme m4-1BB 605:610 arg1 structure 592:600 the crystal structure 580:600 the crystal structure of m4-1BB to 2.2-Å resolution 580:630 Here, using sulfur-SAD phasing, we determined the crystal structure of m4-1BB to 2.2-Å resolution. 29242193 5 2 from structure 825:833 arg1 organization 732:743 the organization 728:743 the organization of CRD1 and the orientation of CRD3 and CRD4 with respect to CRD2 in the m4-1BB structure 728:833 However, the organization of CRD1 and the orientation of CRD3 and CRD4 with respect to CRD2 in the m4-1BB structure distinctly differed from those of other TNFRSFs. 29242193 9 3 theme TNF 1247:1249 arg1 THD 1268:1270 THD 1268:1270 THD 1268:1270 Although the TNF homology domain (THD) of human (h)4-1BBL forms non-covalent trimers, we found that m4-1BBL formed a covalent dimer via 2 cysteines absent in h4-1BBL. 29242193 9 3 theme TNF 1247:1249 arg1 domain 1260:1265 the TNF homology domain 1243:1265 the TNF homology domain (THD) of human (h)4-1BBL 1243:1290 Although the TNF homology domain (THD) of human (h)4-1BBL forms non-covalent trimers, we found that m4-1BBL formed a covalent dimer via 2 cysteines absent in h4-1BBL. 29242193 9 3 theme TNF 1247:1249 arg1 4-1BBL 1285:1290 human (h)4-1BBL 1276:1290 human (h)4-1BBL 1276:1290 Although the TNF homology domain (THD) of human (h)4-1BBL forms non-covalent trimers, we found that m4-1BBL formed a covalent dimer via 2 cysteines absent in h4-1BBL. 29242193 2 4 theme mouse 413:417 arg1 4-1BB 422:426 mouse (m)4-1BB 413:426 mouse (m)4-1BB 413:426 4-1BB also can bind to the tandem repeat-type lectin galectin-9 (Gal-9), and signaling through mouse (m)4-1BB is reduced in galectin-9 (Gal-9)-deficient mice, suggesting a pivotal role of Gal-9 in m4-1BB activation. 29242193 5 5 theme orientation 761:771 arg1 organization 732:743 the organization 728:743 the organization of CRD1 and the orientation of CRD3 and CRD4 with respect to CRD2 in the m4-1BB structure 728:833 However, the organization of CRD1 and the orientation of CRD3 and CRD4 with respect to CRD2 in the m4-1BB structure distinctly differed from those of other TNFRSFs. 29242193 1 6 theme receptor 203:210 arg1 trimerization 212:224 receptor trimerization 203:224 receptor trimerization 203:224 4-1BB (CD137) is a TNF receptor superfamily (TNFRSF) member that is thought to undergo receptor trimerization upon binding to its trimeric TNF superfamily ligand (4-1BBL) to stimulate immune responses. 29242193 9 7 from h4-1BBL 1392:1398 arg1 absent 1382:1387 absent 1382:1387 absent 1382:1387 Although the TNF homology domain (THD) of human (h)4-1BBL forms non-covalent trimers, we found that m4-1BBL formed a covalent dimer via 2 cysteines absent in h4-1BBL. 29242193 6 8 dep glycosylated 951:962 arg1 N-linked 942:949 N-linked 942:949 N-linked 942:949 Moreover, we mapped two Asn residues within CRD4 that are N-linked glycosylated and mediate m4-1BB binding to Gal-9. 29242193 2 9 theme pivotal 490:496 arg1 role 498:501 a pivotal role 488:501 a pivotal role of Gal-9 in m4-1BB activation 488:531 4-1BB also can bind to the tandem repeat-type lectin galectin-9 (Gal-9), and signaling through mouse (m)4-1BB is reduced in galectin-9 (Gal-9)-deficient mice, suggesting a pivotal role of Gal-9 in m4-1BB activation. 29242193 5 10 from orientation 761:771 arg1 structure 825:833 the m4-1BB structure 814:833 the m4-1BB structure 814:833 However, the organization of CRD1 and the orientation of CRD3 and CRD4 with respect to CRD2 in the m4-1BB structure distinctly differed from those of other TNFRSFs. 29242193 9 11 theme covalent 1351:1358 arg1 dimer 1360:1364 a covalent dimer 1349:1364 a covalent dimer 1349:1364 Although the TNF homology domain (THD) of human (h)4-1BBL forms non-covalent trimers, we found that m4-1BBL formed a covalent dimer via 2 cysteines absent in h4-1BBL. 29242193 9 12 theme absent 1382:1387 arg1 cysteines 1372:1380 2 cysteines 1370:1380 2 cysteines absent in h4-1BBL 1370:1398 Although the TNF homology domain (THD) of human (h)4-1BBL forms non-covalent trimers, we found that m4-1BBL formed a covalent dimer via 2 cysteines absent in h4-1BBL. 29242193 5 13 from organization 732:743 arg1 structure 825:833 the m4-1BB structure 814:833 the m4-1BB structure 814:833 However, the organization of CRD1 and the orientation of CRD3 and CRD4 with respect to CRD2 in the m4-1BB structure distinctly differed from those of other TNFRSFs. 29242193 1 14 theme immune 300:305 arg1 responses 307:315 immune responses 300:315 immune responses 300:315 4-1BB (CD137) is a TNF receptor superfamily (TNFRSF) member that is thought to undergo receptor trimerization upon binding to its trimeric TNF superfamily ligand (4-1BBL) to stimulate immune responses. 29242193 7 15 theme binding 1061:1067 arg1 affinity 1069:1076 a very tight nanomolar binding affinity 1038:1076 a very tight nanomolar binding affinity to m4-1BBL 1038:1087 Kinetics studies of m4-1BB disclosed a very tight nanomolar binding affinity to m4-1BBL with an unexpectedly strong avidity effect. 29242193 5 16 from CRD1 748:751 arg1 structure 825:833 the m4-1BB structure 814:833 the m4-1BB structure 814:833 However, the organization of CRD1 and the orientation of CRD3 and CRD4 with respect to CRD2 in the m4-1BB structure distinctly differed from those of other TNFRSFs. 29242193 7 17 theme avidity 1117:1123 arg1 effect 1125:1130 an unexpectedly strong avidity effect 1094:1130 an unexpectedly strong avidity effect 1094:1130 Kinetics studies of m4-1BB disclosed a very tight nanomolar binding affinity to m4-1BBL with an unexpectedly strong avidity effect. 29242193 3 18 theme 2.2-Å 615:619 arg1 resolution 621:630 2.2-Å resolution 615:630 2.2-Å resolution 615:630 Here, using sulfur-SAD phasing, we determined the crystal structure of m4-1BB to 2.2-Å resolution. 29242193 4 19 theme other 658:662 arg1 TNFRSFs 664:670 other TNFRSFs 658:670 other TNFRSFs 658:670 We found that similar to other TNFRSFs, m4-1BB has four cysteine-rich domains (CRDs). 29242193 6 20 theme Asn 908:910 arg1 residues 912:919 two Asn residues 904:919 two Asn residues within CRD4 that are N-linked glycosylated and mediate m4-1BB binding to Gal-9 904:998 Moreover, we mapped two Asn residues within CRD4 that are N-linked glycosylated and mediate m4-1BB binding to Gal-9. 29242193 10 21 theme TNFR 1457:1460 arg1 signaling 1476:1484 TNFR intracellular signaling 1457:1484 TNFR intracellular signaling 1457:1484 As multimerization and clustering is a prerequisite for TNFR intracellular signaling, and as m4-1BBL can only recruit two m4-1BB monomers, we hypothesize that m4-1BBL and Gal-9 act together to aid aggregation of m4-1BB monomers to efficiently initiate m4-1BB signaling. 29242193 2 22 theme m4-1BB 515:520 arg1 activation 522:531 m4-1BB activation 515:531 m4-1BB activation 515:531 4-1BB also can bind to the tandem repeat-type lectin galectin-9 (Gal-9), and signaling through mouse (m)4-1BB is reduced in galectin-9 (Gal-9)-deficient mice, suggesting a pivotal role of Gal-9 in m4-1BB activation. 29242193 7 23 theme m4-1BB 1021:1026 arg1 studies 1010:1016 Kinetics studies 1001:1016 Kinetics studies of m4-1BB 1001:1026 Kinetics studies of m4-1BB disclosed a very tight nanomolar binding affinity to m4-1BBL with an unexpectedly strong avidity effect. 29242193 1 24 theme TNF 135:137 arg1 TNFRSF 161:166 TNFRSF 161:166 TNFRSF 161:166 4-1BB (CD137) is a TNF receptor superfamily (TNFRSF) member that is thought to undergo receptor trimerization upon binding to its trimeric TNF superfamily ligand (4-1BBL) to stimulate immune responses. 29242193 1 24 theme TNF 135:137 arg1 superfamily 148:158 TNF receptor superfamily 135:158 a TNF receptor superfamily (TNFRSF) member that is thought to undergo receptor trimerization upon binding to its trimeric TNF superfamily ligand (4-1BBL) to stimulate immune responses 133:315 4-1BB (CD137) is a TNF receptor superfamily (TNFRSF) member that is thought to undergo receptor trimerization upon binding to its trimeric TNF superfamily ligand (4-1BBL) to stimulate immune responses. 29242193 2 25 from role 498:501 arg1 activation 522:531 m4-1BB activation 515:531 m4-1BB activation 515:531 4-1BB also can bind to the tandem repeat-type lectin galectin-9 (Gal-9), and signaling through mouse (m)4-1BB is reduced in galectin-9 (Gal-9)-deficient mice, suggesting a pivotal role of Gal-9 in m4-1BB activation. 29242193 6 26 gly glycosylated 951:962 arg1 residues 912:919 two Asn residues 904:919 two Asn residues within CRD4 that are N-linked glycosylated and mediate m4-1BB binding to Gal-9 904:998 Moreover, we mapped two Asn residues within CRD4 that are N-linked glycosylated and mediate m4-1BB binding to Gal-9. 29242193 1 27 theme receptor 139:146 arg1 TNFRSF 161:166 TNFRSF 161:166 TNFRSF 161:166 4-1BB (CD137) is a TNF receptor superfamily (TNFRSF) member that is thought to undergo receptor trimerization upon binding to its trimeric TNF superfamily ligand (4-1BBL) to stimulate immune responses. 29242193 1 27 theme receptor 139:146 arg1 superfamily 148:158 TNF receptor superfamily 135:158 a TNF receptor superfamily (TNFRSF) member that is thought to undergo receptor trimerization upon binding to its trimeric TNF superfamily ligand (4-1BBL) to stimulate immune responses 133:315 4-1BB (CD137) is a TNF receptor superfamily (TNFRSF) member that is thought to undergo receptor trimerization upon binding to its trimeric TNF superfamily ligand (4-1BBL) to stimulate immune responses. 29242193 0 28 theme Crystal 0:6 arg1 structure 8:16 Crystal structure 0:16 Crystal structure of murine 4-1BB 0:32 Crystal structure of murine 4-1BB and its interaction with 4-1BBL support a role for galectin-9 in 4-1BB signaling. 29242193 2 29 theme Gal-9 506:510 arg1 role 498:501 a pivotal role 488:501 a pivotal role of Gal-9 in m4-1BB activation 488:531 4-1BB also can bind to the tandem repeat-type lectin galectin-9 (Gal-9), and signaling through mouse (m)4-1BB is reduced in galectin-9 (Gal-9)-deficient mice, suggesting a pivotal role of Gal-9 in m4-1BB activation. 29242193 8 30 theme lower 1196:1200 arg1 affinity 1202:1209 lower affinity 1196:1209 lower affinity 1196:1209 Both N- and C-terminal domains of Gal-9 bound m4-1BB, but with lower affinity compared with m4-1BBL. 29242193 1 31 theme superfamily 148:158 arg1 4-1BB 116:120 4-1BB 116:120 4-1BB (CD137) 116:128 4-1BB (CD137) is a TNF receptor superfamily (TNFRSF) member that is thought to undergo receptor trimerization upon binding to its trimeric TNF superfamily ligand (4-1BBL) to stimulate immune responses. 29242193 1 31 theme superfamily 148:158 arg1 member 169:174 a TNF receptor superfamily (TNFRSF) member 133:174 a TNF receptor superfamily (TNFRSF) member that is thought to undergo receptor trimerization upon binding to its trimeric TNF superfamily ligand (4-1BBL) to stimulate immune responses 133:315 4-1BB (CD137) is a TNF receptor superfamily (TNFRSF) member that is thought to undergo receptor trimerization upon binding to its trimeric TNF superfamily ligand (4-1BBL) to stimulate immune responses. 29242193 0 32 theme murine 21:26 arg1 4-1BB 28:32 murine 4-1BB 21:32 murine 4-1BB 21:32 Crystal structure of murine 4-1BB and its interaction with 4-1BBL support a role for galectin-9 in 4-1BB signaling. 29242193 8 33 theme C-terminal 1145:1154 arg1 Gal-9 1167:1171 Gal-9 1167:1171 Gal-9 1167:1171 Both N- and C-terminal domains of Gal-9 bound m4-1BB, but with lower affinity compared with m4-1BBL. 29242193 8 33 theme C-terminal 1145:1154 arg1 domains 1156:1162 C-terminal domains 1145:1162 C-terminal domains of Gal-9 1145:1171 Both N- and C-terminal domains of Gal-9 bound m4-1BB, but with lower affinity compared with m4-1BBL. 29242193 2 34 theme lectin 364:369 arg1 Gal-9 383:387 Gal-9 383:387 Gal-9 383:387 4-1BB also can bind to the tandem repeat-type lectin galectin-9 (Gal-9), and signaling through mouse (m)4-1BB is reduced in galectin-9 (Gal-9)-deficient mice, suggesting a pivotal role of Gal-9 in m4-1BB activation. 29242193 2 34 theme lectin 364:369 arg1 galectin-9 371:380 the tandem repeat-type lectin galectin-9 341:380 the tandem repeat-type lectin galectin-9 (Gal-9) 341:388 4-1BB also can bind to the tandem repeat-type lectin galectin-9 (Gal-9), and signaling through mouse (m)4-1BB is reduced in galectin-9 (Gal-9)-deficient mice, suggesting a pivotal role of Gal-9 in m4-1BB activation. 29242193 0 35 theme 4-1BB 99:103 arg1 signaling 105:113 4-1BB signaling 99:113 4-1BB signaling 99:113 Crystal structure of murine 4-1BB and its interaction with 4-1BBL support a role for galectin-9 in 4-1BB signaling. 29242193 8 36 theme Gal-9 1167:1171 arg1 Gal-9 1167:1171 Gal-9 1167:1171 Gal-9 1167:1171 Both N- and C-terminal domains of Gal-9 bound m4-1BB, but with lower affinity compared with m4-1BBL. 29242193 8 36 theme Gal-9 1167:1171 arg1 N- 1138:1139 N- 1138:1139 N- 1138:1139 Both N- and C-terminal domains of Gal-9 bound m4-1BB, but with lower affinity compared with m4-1BBL. 29242193 8 36 theme Gal-9 1167:1171 arg1 domains 1156:1162 C-terminal domains 1145:1162 C-terminal domains of Gal-9 1145:1171 Both N- and C-terminal domains of Gal-9 bound m4-1BB, but with lower affinity compared with m4-1BBL. 29242193 2 37 theme repeat-type 352:362 arg1 Gal-9 383:387 Gal-9 383:387 Gal-9 383:387 4-1BB also can bind to the tandem repeat-type lectin galectin-9 (Gal-9), and signaling through mouse (m)4-1BB is reduced in galectin-9 (Gal-9)-deficient mice, suggesting a pivotal role of Gal-9 in m4-1BB activation. 29242193 2 37 theme repeat-type 352:362 arg1 galectin-9 371:380 the tandem repeat-type lectin galectin-9 341:380 the tandem repeat-type lectin galectin-9 (Gal-9) 341:388 4-1BB also can bind to the tandem repeat-type lectin galectin-9 (Gal-9), and signaling through mouse (m)4-1BB is reduced in galectin-9 (Gal-9)-deficient mice, suggesting a pivotal role of Gal-9 in m4-1BB activation. 29242193 1 38 theme trimeric 246:253 arg1 4-1BBL 279:284 4-1BBL 279:284 4-1BBL 279:284 4-1BB (CD137) is a TNF receptor superfamily (TNFRSF) member that is thought to undergo receptor trimerization upon binding to its trimeric TNF superfamily ligand (4-1BBL) to stimulate immune responses. 29242193 1 38 theme trimeric 246:253 arg1 ligand 271:276 its trimeric TNF superfamily ligand 242:276 its trimeric TNF superfamily ligand (4-1BBL) 242:285 4-1BB (CD137) is a TNF receptor superfamily (TNFRSF) member that is thought to undergo receptor trimerization upon binding to its trimeric TNF superfamily ligand (4-1BBL) to stimulate immune responses. 29242193 9 39 theme non-covalent 1298:1309 arg1 trimers 1311:1317 non-covalent trimers 1298:1317 non-covalent trimers 1298:1317 Although the TNF homology domain (THD) of human (h)4-1BBL forms non-covalent trimers, we found that m4-1BBL formed a covalent dimer via 2 cysteines absent in h4-1BBL. 29242193 10 40 theme m4-1BB 1653:1658 arg1 signaling 1660:1668 m4-1BB signaling 1653:1668 m4-1BB signaling 1653:1668 As multimerization and clustering is a prerequisite for TNFR intracellular signaling, and as m4-1BBL can only recruit two m4-1BB monomers, we hypothesize that m4-1BBL and Gal-9 act together to aid aggregation of m4-1BB monomers to efficiently initiate m4-1BB signaling. 29242193 4 41 theme cysteine-rich 689:701 arg1 CRDs 712:715 CRDs 712:715 CRDs 712:715 We found that similar to other TNFRSFs, m4-1BB has four cysteine-rich domains (CRDs). 29242193 4 41 theme cysteine-rich 689:701 arg1 domains 703:709 four cysteine-rich domains 684:709 four cysteine-rich domains (CRDs) 684:716 We found that similar to other TNFRSFs, m4-1BB has four cysteine-rich domains (CRDs). 29242193 9 42 theme human 1276:1280 arg1 4-1BBL 1285:1290 human (h)4-1BBL 1276:1290 human (h)4-1BBL 1276:1290 Although the TNF homology domain (THD) of human (h)4-1BBL forms non-covalent trimers, we found that m4-1BBL formed a covalent dimer via 2 cysteines absent in h4-1BBL. 29242193 2 43 theme tandem 345:350 arg1 Gal-9 383:387 Gal-9 383:387 Gal-9 383:387 4-1BB also can bind to the tandem repeat-type lectin galectin-9 (Gal-9), and signaling through mouse (m)4-1BB is reduced in galectin-9 (Gal-9)-deficient mice, suggesting a pivotal role of Gal-9 in m4-1BB activation. 29242193 2 43 theme tandem 345:350 arg1 galectin-9 371:380 the tandem repeat-type lectin galectin-9 341:380 the tandem repeat-type lectin galectin-9 (Gal-9) 341:388 4-1BB also can bind to the tandem repeat-type lectin galectin-9 (Gal-9), and signaling through mouse (m)4-1BB is reduced in galectin-9 (Gal-9)-deficient mice, suggesting a pivotal role of Gal-9 in m4-1BB activation. 29242193 0 44 theme 4-1BB 28:32 arg1 structure 8:16 Crystal structure 0:16 Crystal structure of murine 4-1BB 0:32 Crystal structure of murine 4-1BB and its interaction with 4-1BBL support a role for galectin-9 in 4-1BB signaling. 29242193 0 44 theme 4-1BB 28:32 arg1 interaction 42:52 its interaction 38:52 its interaction with 4-1BBL 38:64 Crystal structure of murine 4-1BB and its interaction with 4-1BBL support a role for galectin-9 in 4-1BB signaling. 29242193 1 45 theme TNF 255:257 arg1 superfamily 259:269 TNF superfamily 255:269 its trimeric TNF superfamily ligand (4-1BBL) 242:285 4-1BB (CD137) is a TNF receptor superfamily (TNFRSF) member that is thought to undergo receptor trimerization upon binding to its trimeric TNF superfamily ligand (4-1BBL) to stimulate immune responses. 29242193 9 46 theme homology 1251:1258 arg1 THD 1268:1270 THD 1268:1270 THD 1268:1270 Although the TNF homology domain (THD) of human (h)4-1BBL forms non-covalent trimers, we found that m4-1BBL formed a covalent dimer via 2 cysteines absent in h4-1BBL. 29242193 9 46 theme homology 1251:1258 arg1 domain 1260:1265 the TNF homology domain 1243:1265 the TNF homology domain (THD) of human (h)4-1BBL 1243:1290 Although the TNF homology domain (THD) of human (h)4-1BBL forms non-covalent trimers, we found that m4-1BBL formed a covalent dimer via 2 cysteines absent in h4-1BBL. 29242193 9 46 theme homology 1251:1258 arg1 4-1BBL 1285:1290 human (h)4-1BBL 1276:1290 human (h)4-1BBL 1276:1290 Although the TNF homology domain (THD) of human (h)4-1BBL forms non-covalent trimers, we found that m4-1BBL formed a covalent dimer via 2 cysteines absent in h4-1BBL. 29242193 5 47 theme other 869:873 arg1 TNFRSFs 875:881 other TNFRSFs 869:881 other TNFRSFs 869:881 However, the organization of CRD1 and the orientation of CRD3 and CRD4 with respect to CRD2 in the m4-1BB structure distinctly differed from those of other TNFRSFs. 29242193 9 48 theme 4-1BBL 1285:1290 arg1 THD 1268:1270 THD 1268:1270 THD 1268:1270 Although the TNF homology domain (THD) of human (h)4-1BBL forms non-covalent trimers, we found that m4-1BBL formed a covalent dimer via 2 cysteines absent in h4-1BBL. 29242193 9 48 theme 4-1BBL 1285:1290 arg1 domain 1260:1265 the TNF homology domain 1243:1265 the TNF homology domain (THD) of human (h)4-1BBL 1243:1290 Although the TNF homology domain (THD) of human (h)4-1BBL forms non-covalent trimers, we found that m4-1BBL formed a covalent dimer via 2 cysteines absent in h4-1BBL. 29242193 9 48 theme 4-1BBL 1285:1290 arg1 4-1BBL 1285:1290 human (h)4-1BBL 1276:1290 human (h)4-1BBL 1276:1290 Although the TNF homology domain (THD) of human (h)4-1BBL forms non-covalent trimers, we found that m4-1BBL formed a covalent dimer via 2 cysteines absent in h4-1BBL. 29242193 1 49 theme superfamily 259:269 arg1 4-1BBL 279:284 4-1BBL 279:284 4-1BBL 279:284 4-1BB (CD137) is a TNF receptor superfamily (TNFRSF) member that is thought to undergo receptor trimerization upon binding to its trimeric TNF superfamily ligand (4-1BBL) to stimulate immune responses. 29242193 1 49 theme superfamily 259:269 arg1 ligand 271:276 its trimeric TNF superfamily ligand 242:276 its trimeric TNF superfamily ligand (4-1BBL) 242:285 4-1BB (CD137) is a TNF receptor superfamily (TNFRSF) member that is thought to undergo receptor trimerization upon binding to its trimeric TNF superfamily ligand (4-1BBL) to stimulate immune responses. 29242193 10 50 theme monomers 1620:1627 arg1 aggregation 1598:1608 aggregation 1598:1608 aggregation of m4-1BB monomers to efficiently initiate m4-1BB signaling 1598:1668 As multimerization and clustering is a prerequisite for TNFR intracellular signaling, and as m4-1BBL can only recruit two m4-1BB monomers, we hypothesize that m4-1BBL and Gal-9 act together to aid aggregation of m4-1BB monomers to efficiently initiate m4-1BB signaling. 29242193 6 51 theme m4-1BB 976:981 arg1 binding 983:989 m4-1BB binding 976:989 m4-1BB binding to Gal-9 976:998 Moreover, we mapped two Asn residues within CRD4 that are N-linked glycosylated and mediate m4-1BB binding to Gal-9. 29242193 10 52 theme intracellular 1462:1474 arg1 signaling 1476:1484 TNFR intracellular signaling 1457:1484 TNFR intracellular signaling 1457:1484 As multimerization and clustering is a prerequisite for TNFR intracellular signaling, and as m4-1BBL can only recruit two m4-1BB monomers, we hypothesize that m4-1BBL and Gal-9 act together to aid aggregation of m4-1BB monomers to efficiently initiate m4-1BB signaling. 29242193 0 53 with structure 8:16 arg1 4-1BBL 59:64 4-1BBL 59:64 4-1BBL 59:64 Crystal structure of murine 4-1BB and its interaction with 4-1BBL support a role for galectin-9 in 4-1BB signaling. 29242193 5 54 theme CRD3 776:779 arg1 CRD1 748:751 CRD1 748:751 CRD1 748:751 However, the organization of CRD1 and the orientation of CRD3 and CRD4 with respect to CRD2 in the m4-1BB structure distinctly differed from those of other TNFRSFs. 29242193 5 54 theme CRD3 776:779 arg1 orientation 761:771 the orientation 757:771 the orientation of CRD3 and CRD4 with respect to CRD2 in the m4-1BB structure 757:833 However, the organization of CRD1 and the orientation of CRD3 and CRD4 with respect to CRD2 in the m4-1BB structure distinctly differed from those of other TNFRSFs. 29242193 7 55 theme Kinetics 1001:1008 arg1 studies 1010:1016 Kinetics studies 1001:1016 Kinetics studies of m4-1BB 1001:1026 Kinetics studies of m4-1BB disclosed a very tight nanomolar binding affinity to m4-1BBL with an unexpectedly strong avidity effect. 29242193 9 56 dep human 1276:1280 arg1 h 1283:1283 h 1283:1283 h 1283:1283 Although the TNF homology domain (THD) of human (h)4-1BBL forms non-covalent trimers, we found that m4-1BBL formed a covalent dimer via 2 cysteines absent in h4-1BBL. 29242193 7 57 theme strong 1110:1115 arg1 effect 1125:1130 an unexpectedly strong avidity effect 1094:1130 an unexpectedly strong avidity effect 1094:1130 Kinetics studies of m4-1BB disclosed a very tight nanomolar binding affinity to m4-1BBL with an unexpectedly strong avidity effect. 29242193 9 58 from absent 1382:1387 arg1 h4-1BBL 1392:1398 h4-1BBL 1392:1398 h4-1BBL 1392:1398 Although the TNF homology domain (THD) of human (h)4-1BBL forms non-covalent trimers, we found that m4-1BBL formed a covalent dimer via 2 cysteines absent in h4-1BBL. 29242193 2 59 theme -deficient 460:469 arg1 mice 471:474 galectin-9 (Gal-9)-deficient mice 442:474 galectin-9 (Gal-9)-deficient mice 442:474 4-1BB also can bind to the tandem repeat-type lectin galectin-9 (Gal-9), and signaling through mouse (m)4-1BB is reduced in galectin-9 (Gal-9)-deficient mice, suggesting a pivotal role of Gal-9 in m4-1BB activation. 29242193 3 60 theme sulfur-SAD 546:555 arg1 phasing 557:563 sulfur-SAD phasing 546:563 sulfur-SAD phasing 546:563 Here, using sulfur-SAD phasing, we determined the crystal structure of m4-1BB to 2.2-Å resolution. 29242193 5 61 theme m4-1BB 818:823 arg1 structure 825:833 the m4-1BB structure 814:833 the m4-1BB structure 814:833 However, the organization of CRD1 and the orientation of CRD3 and CRD4 with respect to CRD2 in the m4-1BB structure distinctly differed from those of other TNFRSFs. 29242193 0 62 with interaction 42:52 arg1 4-1BBL 59:64 4-1BBL 59:64 4-1BBL 59:64 Crystal structure of murine 4-1BB and its interaction with 4-1BBL support a role for galectin-9 in 4-1BB signaling. 29242193 5 63 theme CRD4 785:788 arg1 CRD1 748:751 CRD1 748:751 CRD1 748:751 However, the organization of CRD1 and the orientation of CRD3 and CRD4 with respect to CRD2 in the m4-1BB structure distinctly differed from those of other TNFRSFs. 29242193 5 63 theme CRD4 785:788 arg1 orientation 761:771 the orientation 757:771 the orientation of CRD3 and CRD4 with respect to CRD2 in the m4-1BB structure 757:833 However, the organization of CRD1 and the orientation of CRD3 and CRD4 with respect to CRD2 in the m4-1BB structure distinctly differed from those of other TNFRSFs. 29242193 4 64 contain has 680:682 arg1 m4-1BB 673:678 m4-1BB 673:678 m4-1BB 673:678 We found that similar to other TNFRSFs, m4-1BB has four cysteine-rich domains (CRDs). 29242193 4 64 contain has 680:682 arg2 CRDs 712:715 CRDs 712:715 CRDs 712:715 We found that similar to other TNFRSFs, m4-1BB has four cysteine-rich domains (CRDs). 29242193 4 64 contain has 680:682 arg2 domains 703:709 four cysteine-rich domains 684:709 four cysteine-rich domains (CRDs) 684:716 We found that similar to other TNFRSFs, m4-1BB has four cysteine-rich domains (CRDs). 29242193 0 65 from role 76:79 arg1 signaling 105:113 4-1BB signaling 99:113 4-1BB signaling 99:113 Crystal structure of murine 4-1BB and its interaction with 4-1BBL support a role for galectin-9 in 4-1BB signaling. 29242193 10 66 theme m4-1BB 1613:1618 arg1 monomers 1620:1627 m4-1BB monomers 1613:1627 m4-1BB monomers 1613:1627 As multimerization and clustering is a prerequisite for TNFR intracellular signaling, and as m4-1BBL can only recruit two m4-1BB monomers, we hypothesize that m4-1BBL and Gal-9 act together to aid aggregation of m4-1BB monomers to efficiently initiate m4-1BB signaling. 29242193 5 67 theme CRD1 748:751 arg1 organization 732:743 the organization 728:743 the organization of CRD1 and the orientation of CRD3 and CRD4 with respect to CRD2 in the m4-1BB structure 728:833 However, the organization of CRD1 and the orientation of CRD3 and CRD4 with respect to CRD2 in the m4-1BB structure distinctly differed from those of other TNFRSFs. 29242193 2 68 theme m 420:420 arg1 4-1BB 422:426 mouse (m)4-1BB 413:426 mouse (m)4-1BB 413:426 4-1BB also can bind to the tandem repeat-type lectin galectin-9 (Gal-9), and signaling through mouse (m)4-1BB is reduced in galectin-9 (Gal-9)-deficient mice, suggesting a pivotal role of Gal-9 in m4-1BB activation. 29242193 3 69 theme crystal 584:590 arg1 structure 592:600 the crystal structure 580:600 the crystal structure of m4-1BB to 2.2-Å resolution 580:630 Here, using sulfur-SAD phasing, we determined the crystal structure of m4-1BB to 2.2-Å resolution. 29242193 10 70 theme m4-1BB 1523:1528 arg1 monomers 1530:1537 two m4-1BB monomers 1519:1537 two m4-1BB monomers 1519:1537 As multimerization and clustering is a prerequisite for TNFR intracellular signaling, and as m4-1BBL can only recruit two m4-1BB monomers, we hypothesize that m4-1BBL and Gal-9 act together to aid aggregation of m4-1BB monomers to efficiently initiate m4-1BB signaling. 29242193 7 71 theme tight 1045:1049 arg1 affinity 1069:1076 a very tight nanomolar binding affinity 1038:1076 a very tight nanomolar binding affinity to m4-1BBL 1038:1087 Kinetics studies of m4-1BB disclosed a very tight nanomolar binding affinity to m4-1BBL with an unexpectedly strong avidity effect. 27479005 7 0 from 1976 1177:1180 arg1 1995 1207:1210 1995 1207:1210 1995 1207:1210 We conclude that: 1) the common practice of rooting the phylogeny of EBOV between the first known outbreak in 1976 and the next outbreak in 1995 provides a misleading view of EBOV evolution that ignores the fact that there is a non-human EBOV host between outbreaks; 2) the N-terminus of GP1 may be constrained from evolving in response to the host immune system by the highly expressed, secreted glycoprotein, which is encoded by the same region of the GP gene; 3) although the mucin-like domain of GP1 is essential for EBOV in vivo, it evolves rapidly without losing its twin functions: providing O-linked glycosylation sites and a flexible surface. 27479005 4 1 theme spike 605:609 arg1 one 580:582 one 580:582 one 580:582 We have focused this study on the evolution of the EBOV glycoprotein gene (GP) because one of its products, the spike glycoprotein (GP1,2), is central to the host immune response and because it contains a large amount of the phylogenetic signal for this virus. 27479005 4 1 theme spike 605:609 arg1 products 591:598 its products 587:598 its products 587:598 We have focused this study on the evolution of the EBOV glycoprotein gene (GP) because one of its products, the spike glycoprotein (GP1,2), is central to the host immune response and because it contains a large amount of the phylogenetic signal for this virus. 27479005 4 1 theme spike 605:609 arg1 GP1,2 625:629 GP1,2 625:629 GP1,2 625:629 We have focused this study on the evolution of the EBOV glycoprotein gene (GP) because one of its products, the spike glycoprotein (GP1,2), is central to the host immune response and because it contains a large amount of the phylogenetic signal for this virus. 27479005 4 1 theme spike 605:609 arg1 glycoprotein 611:622 the spike glycoprotein 601:622 the spike glycoprotein (GP1,2) 601:630 We have focused this study on the evolution of the EBOV glycoprotein gene (GP) because one of its products, the spike glycoprotein (GP1,2), is central to the host immune response and because it contains a large amount of the phylogenetic signal for this virus. 27479005 1 2 from outbreak 72:79 arg1 Africa 115:120 Africa 115:120 Africa 115:120 Since the recent devastating outbreak of Ebola virus disease in western Africa, there has been significant effort to understand the evolution of the deadly virus that caused the outbreak. 27479005 7 3 theme O-linked 1666:1673 arg1 sites 1689:1693 O-linked glycosylation sites 1666:1693 O-linked glycosylation sites 1666:1693 We conclude that: 1) the common practice of rooting the phylogeny of EBOV between the first known outbreak in 1976 and the next outbreak in 1995 provides a misleading view of EBOV evolution that ignores the fact that there is a non-human EBOV host between outbreaks; 2) the N-terminus of GP1 may be constrained from evolving in response to the host immune system by the highly expressed, secreted glycoprotein, which is encoded by the same region of the GP gene; 3) although the mucin-like domain of GP1 is essential for EBOV in vivo, it evolves rapidly without losing its twin functions: providing O-linked glycosylation sites and a flexible surface. 27479005 0 4 from Perspectives 4:15 arg1 Evolution 32:40 Ebola Virus Evolution 20:40 Ebola Virus Evolution 20:40 New Perspectives on Ebola Virus Evolution. 27479005 7 5 theme flexible 1701:1708 arg1 surface 1710:1716 a flexible surface 1699:1716 a flexible surface 1699:1716 We conclude that: 1) the common practice of rooting the phylogeny of EBOV between the first known outbreak in 1976 and the next outbreak in 1995 provides a misleading view of EBOV evolution that ignores the fact that there is a non-human EBOV host between outbreaks; 2) the N-terminus of GP1 may be constrained from evolving in response to the host immune system by the highly expressed, secreted glycoprotein, which is encoded by the same region of the GP gene; 3) although the mucin-like domain of GP1 is essential for EBOV in vivo, it evolves rapidly without losing its twin functions: providing O-linked glycosylation sites and a flexible surface. 27479005 5 6 theme maximum 770:776 arg1 phylogeny 789:797 the maximum likelihood phylogeny 766:797 the maximum likelihood phylogeny of 96 nonredundant GP gene sequences representing each of the outbreaks since 1976 up to the end of 2014 766:902 We inferred the maximum likelihood phylogeny of 96 nonredundant GP gene sequences representing each of the outbreaks since 1976 up to the end of 2014. 27479005 1 7 theme significant 138:148 arg1 effort 150:155 significant effort 138:155 significant effort to understand the evolution of the deadly virus that caused the outbreak 138:228 Since the recent devastating outbreak of Ebola virus disease in western Africa, there has been significant effort to understand the evolution of the deadly virus that caused the outbreak. 27479005 5 8 theme gene 821:824 arg1 sequences 826:834 96 nonredundant GP gene sequences 802:834 96 nonredundant GP gene sequences representing each of the outbreaks since 1976 up to the end of 2014 802:902 We inferred the maximum likelihood phylogeny of 96 nonredundant GP gene sequences representing each of the outbreaks since 1976 up to the end of 2014. 27479005 7 9 theme non-human 1295:1303 arg1 host 1310:1313 a non-human EBOV host 1293:1313 a non-human EBOV host between outbreaks 1293:1331 We conclude that: 1) the common practice of rooting the phylogeny of EBOV between the first known outbreak in 1976 and the next outbreak in 1995 provides a misleading view of EBOV evolution that ignores the fact that there is a non-human EBOV host between outbreaks; 2) the N-terminus of GP1 may be constrained from evolving in response to the host immune system by the highly expressed, secreted glycoprotein, which is encoded by the same region of the GP gene; 3) although the mucin-like domain of GP1 is essential for EBOV in vivo, it evolves rapidly without losing its twin functions: providing O-linked glycosylation sites and a flexible surface. 27479005 7 10 dep system 1423:1428 arg1 response 1395:1402 response 1395:1402 response 1395:1402 We conclude that: 1) the common practice of rooting the phylogeny of EBOV between the first known outbreak in 1976 and the next outbreak in 1995 provides a misleading view of EBOV evolution that ignores the fact that there is a non-human EBOV host between outbreaks; 2) the N-terminus of GP1 may be constrained from evolving in response to the host immune system by the highly expressed, secreted glycoprotein, which is encoded by the same region of the GP gene; 3) although the mucin-like domain of GP1 is essential for EBOV in vivo, it evolves rapidly without losing its twin functions: providing O-linked glycosylation sites and a flexible surface. 27479005 4 11 theme host 651:654 arg1 response 663:670 the host immune response 647:670 the host immune response 647:670 We have focused this study on the evolution of the EBOV glycoprotein gene (GP) because one of its products, the spike glycoprotein (GP1,2), is central to the host immune response and because it contains a large amount of the phylogenetic signal for this virus. 27479005 7 12 theme GP1 1355:1357 arg1 N-terminus 1341:1350 the N-terminus 1337:1350 the N-terminus of GP1 1337:1357 We conclude that: 1) the common practice of rooting the phylogeny of EBOV between the first known outbreak in 1976 and the next outbreak in 1995 provides a misleading view of EBOV evolution that ignores the fact that there is a non-human EBOV host between outbreaks; 2) the N-terminus of GP1 may be constrained from evolving in response to the host immune system by the highly expressed, secreted glycoprotein, which is encoded by the same region of the GP gene; 3) although the mucin-like domain of GP1 is essential for EBOV in vivo, it evolves rapidly without losing its twin functions: providing O-linked glycosylation sites and a flexible surface. 27479005 5 13 theme GP 818:819 arg1 sequences 826:834 96 nonredundant GP gene sequences 802:834 96 nonredundant GP gene sequences representing each of the outbreaks since 1976 up to the end of 2014 802:902 We inferred the maximum likelihood phylogeny of 96 nonredundant GP gene sequences representing each of the outbreaks since 1976 up to the end of 2014. 27479005 1 14 theme recent 53:58 arg1 outbreak 72:79 the recent devastating outbreak 49:79 the recent devastating outbreak of Ebola virus disease in western Africa 49:120 Since the recent devastating outbreak of Ebola virus disease in western Africa, there has been significant effort to understand the evolution of the deadly virus that caused the outbreak. 27479005 7 15 theme common 1092:1097 arg1 practice 1099:1106 the common practice 1088:1106 the common practice of rooting the phylogeny of EBOV between the first known outbreak in 1976 and the next outbreak in 1995 1088:1210 We conclude that: 1) the common practice of rooting the phylogeny of EBOV between the first known outbreak in 1976 and the next outbreak in 1995 provides a misleading view of EBOV evolution that ignores the fact that there is a non-human EBOV host between outbreaks; 2) the N-terminus of GP1 may be constrained from evolving in response to the host immune system by the highly expressed, secreted glycoprotein, which is encoded by the same region of the GP gene; 3) although the mucin-like domain of GP1 is essential for EBOV in vivo, it evolves rapidly without losing its twin functions: providing O-linked glycosylation sites and a flexible surface. 27479005 2 16 theme considerable 248:259 arg1 investment 261:270 a considerable investment 246:270 a considerable investment in sequencing Ebola virus (EBOV) isolates 246:312 There has been a considerable investment in sequencing Ebola virus (EBOV) isolates, and the results paint an important picture of how the virus has spread in western Africa. 27479005 5 17 theme nonredundant 805:816 arg1 sequences 826:834 96 nonredundant GP gene sequences 802:834 96 nonredundant GP gene sequences representing each of the outbreaks since 1976 up to the end of 2014 802:902 We inferred the maximum likelihood phylogeny of 96 nonredundant GP gene sequences representing each of the outbreaks since 1976 up to the end of 2014. 27479005 4 18 theme phylogenetic 718:729 arg1 signal 731:736 the phylogenetic signal 714:736 the phylogenetic signal for this virus 714:751 We have focused this study on the evolution of the EBOV glycoprotein gene (GP) because one of its products, the spike glycoprotein (GP1,2), is central to the host immune response and because it contains a large amount of the phylogenetic signal for this virus. 27479005 4 19 gly glycoprotein 549:560 arg1 glycoprotein 549:560 the EBOV glycoprotein gene 540:565 the EBOV glycoprotein gene (GP) 540:570 We have focused this study on the evolution of the EBOV glycoprotein gene (GP) because one of its products, the spike glycoprotein (GP1,2), is central to the host immune response and because it contains a large amount of the phylogenetic signal for this virus. 27479005 1 20 theme devastating 60:70 arg1 outbreak 72:79 the recent devastating outbreak 49:79 the recent devastating outbreak of Ebola virus disease in western Africa 49:120 Since the recent devastating outbreak of Ebola virus disease in western Africa, there has been significant effort to understand the evolution of the deadly virus that caused the outbreak. 27479005 7 21 theme known 1159:1163 arg1 outbreak 1165:1172 the first known outbreak 1149:1172 the first known outbreak in 1976 and the next outbreak in 1995 1149:1210 We conclude that: 1) the common practice of rooting the phylogeny of EBOV between the first known outbreak in 1976 and the next outbreak in 1995 provides a misleading view of EBOV evolution that ignores the fact that there is a non-human EBOV host between outbreaks; 2) the N-terminus of GP1 may be constrained from evolving in response to the host immune system by the highly expressed, secreted glycoprotein, which is encoded by the same region of the GP gene; 3) although the mucin-like domain of GP1 is essential for EBOV in vivo, it evolves rapidly without losing its twin functions: providing O-linked glycosylation sites and a flexible surface. 27479005 7 22 gly glycosylation 1675:1687 arg2 sites 1689:1693 O-linked glycosylation sites 1666:1693 O-linked glycosylation sites 1666:1693 We conclude that: 1) the common practice of rooting the phylogeny of EBOV between the first known outbreak in 1976 and the next outbreak in 1995 provides a misleading view of EBOV evolution that ignores the fact that there is a non-human EBOV host between outbreaks; 2) the N-terminus of GP1 may be constrained from evolving in response to the host immune system by the highly expressed, secreted glycoprotein, which is encoded by the same region of the GP gene; 3) although the mucin-like domain of GP1 is essential for EBOV in vivo, it evolves rapidly without losing its twin functions: providing O-linked glycosylation sites and a flexible surface. 27479005 4 23 from study 514:518 arg1 evolution 527:535 the evolution 523:535 the evolution of the EBOV glycoprotein gene (GP) 523:570 We have focused this study on the evolution of the EBOV glycoprotein gene (GP) because one of its products, the spike glycoprotein (GP1,2), is central to the host immune response and because it contains a large amount of the phylogenetic signal for this virus. 27479005 5 24 theme likelihood 778:787 arg1 phylogeny 789:797 the maximum likelihood phylogeny 766:797 the maximum likelihood phylogeny of 96 nonredundant GP gene sequences representing each of the outbreaks since 1976 up to the end of 2014 766:902 We inferred the maximum likelihood phylogeny of 96 nonredundant GP gene sequences representing each of the outbreaks since 1976 up to the end of 2014. 27479005 7 25 theme glycosylation 1675:1687 arg1 sites 1689:1693 O-linked glycosylation sites 1666:1693 O-linked glycosylation sites 1666:1693 We conclude that: 1) the common practice of rooting the phylogeny of EBOV between the first known outbreak in 1976 and the next outbreak in 1995 provides a misleading view of EBOV evolution that ignores the fact that there is a non-human EBOV host between outbreaks; 2) the N-terminus of GP1 may be constrained from evolving in response to the host immune system by the highly expressed, secreted glycoprotein, which is encoded by the same region of the GP gene; 3) although the mucin-like domain of GP1 is essential for EBOV in vivo, it evolves rapidly without losing its twin functions: providing O-linked glycosylation sites and a flexible surface. 27479005 7 26 theme first 1153:1157 arg1 outbreak 1165:1172 the first known outbreak 1149:1172 the first known outbreak in 1976 and the next outbreak in 1995 1149:1210 We conclude that: 1) the common practice of rooting the phylogeny of EBOV between the first known outbreak in 1976 and the next outbreak in 1995 provides a misleading view of EBOV evolution that ignores the fact that there is a non-human EBOV host between outbreaks; 2) the N-terminus of GP1 may be constrained from evolving in response to the host immune system by the highly expressed, secreted glycoprotein, which is encoded by the same region of the GP gene; 3) although the mucin-like domain of GP1 is essential for EBOV in vivo, it evolves rapidly without losing its twin functions: providing O-linked glycosylation sites and a flexible surface. 27479005 4 27 theme immune 656:661 arg1 response 663:670 the host immune response 647:670 the host immune response 647:670 We have focused this study on the evolution of the EBOV glycoprotein gene (GP) because one of its products, the spike glycoprotein (GP1,2), is central to the host immune response and because it contains a large amount of the phylogenetic signal for this virus. 27479005 7 28 theme twin 1640:1643 arg1 functions 1645:1653 its twin functions 1636:1653 its twin functions 1636:1653 We conclude that: 1) the common practice of rooting the phylogeny of EBOV between the first known outbreak in 1976 and the next outbreak in 1995 provides a misleading view of EBOV evolution that ignores the fact that there is a non-human EBOV host between outbreaks; 2) the N-terminus of GP1 may be constrained from evolving in response to the host immune system by the highly expressed, secreted glycoprotein, which is encoded by the same region of the GP gene; 3) although the mucin-like domain of GP1 is essential for EBOV in vivo, it evolves rapidly without losing its twin functions: providing O-linked glycosylation sites and a flexible surface. 27479005 2 29 theme important 340:348 arg1 picture 350:356 an important picture 337:356 an important picture of how the virus has spread in western Africa 337:402 There has been a considerable investment in sequencing Ebola virus (EBOV) isolates, and the results paint an important picture of how the virus has spread in western Africa. 27479005 7 30 theme gene 1524:1527 arg1 region 1507:1512 the same region 1498:1512 the same region of the GP gene 1498:1527 We conclude that: 1) the common practice of rooting the phylogeny of EBOV between the first known outbreak in 1976 and the next outbreak in 1995 provides a misleading view of EBOV evolution that ignores the fact that there is a non-human EBOV host between outbreaks; 2) the N-terminus of GP1 may be constrained from evolving in response to the host immune system by the highly expressed, secreted glycoprotein, which is encoded by the same region of the GP gene; 3) although the mucin-like domain of GP1 is essential for EBOV in vivo, it evolves rapidly without losing its twin functions: providing O-linked glycosylation sites and a flexible surface. 27479005 2 31 theme virus 292:296 arg1 isolates 305:312 sequencing Ebola virus (EBOV) isolates 275:312 sequencing Ebola virus (EBOV) isolates 275:312 There has been a considerable investment in sequencing Ebola virus (EBOV) isolates, and the results paint an important picture of how the virus has spread in western Africa. 27479005 7 32 from outbreak 1195:1202 arg1 1995 1207:1210 1995 1207:1210 1995 1207:1210 We conclude that: 1) the common practice of rooting the phylogeny of EBOV between the first known outbreak in 1976 and the next outbreak in 1995 provides a misleading view of EBOV evolution that ignores the fact that there is a non-human EBOV host between outbreaks; 2) the N-terminus of GP1 may be constrained from evolving in response to the host immune system by the highly expressed, secreted glycoprotein, which is encoded by the same region of the GP gene; 3) although the mucin-like domain of GP1 is essential for EBOV in vivo, it evolves rapidly without losing its twin functions: providing O-linked glycosylation sites and a flexible surface. 27479005 7 33 link O-linked 1666:1673 arg1 sites 1689:1693 O-linked glycosylation sites 1666:1693 O-linked glycosylation sites 1666:1693 We conclude that: 1) the common practice of rooting the phylogeny of EBOV between the first known outbreak in 1976 and the next outbreak in 1995 provides a misleading view of EBOV evolution that ignores the fact that there is a non-human EBOV host between outbreaks; 2) the N-terminus of GP1 may be constrained from evolving in response to the host immune system by the highly expressed, secreted glycoprotein, which is encoded by the same region of the GP gene; 3) although the mucin-like domain of GP1 is essential for EBOV in vivo, it evolves rapidly without losing its twin functions: providing O-linked glycosylation sites and a flexible surface. 27479005 0 34 theme New 0:2 arg1 Perspectives 4:15 New Perspectives 0:15 New Perspectives on Ebola Virus Evolution. 0:41 New Perspectives on Ebola Virus Evolution. 27479005 4 35 theme signal 731:736 arg1 signal 731:736 the phylogenetic signal 714:736 the phylogenetic signal for this virus 714:751 We have focused this study on the evolution of the EBOV glycoprotein gene (GP) because one of its products, the spike glycoprotein (GP1,2), is central to the host immune response and because it contains a large amount of the phylogenetic signal for this virus. 27479005 4 35 theme signal 731:736 arg1 amount 704:709 a large amount 696:709 a large amount of the phylogenetic signal for this virus 696:751 We have focused this study on the evolution of the EBOV glycoprotein gene (GP) because one of its products, the spike glycoprotein (GP1,2), is central to the host immune response and because it contains a large amount of the phylogenetic signal for this virus. 27479005 1 36 theme Ebola 84:88 arg1 virus 90:94 Ebola virus 84:94 Ebola virus disease 84:102 Since the recent devastating outbreak of Ebola virus disease in western Africa, there has been significant effort to understand the evolution of the deadly virus that caused the outbreak. 27479005 5 37 dep end 892:894 arg1 up 882:883 up 882:883 up 882:883 We inferred the maximum likelihood phylogeny of 96 nonredundant GP gene sequences representing each of the outbreaks since 1976 up to the end of 2014. 27479005 0 38 theme Ebola 20:24 arg1 Evolution 32:40 Ebola Virus Evolution 20:40 Ebola Virus Evolution 20:40 New Perspectives on Ebola Virus Evolution. 27479005 7 39 theme EBOV 1242:1245 arg1 evolution 1247:1255 EBOV evolution 1242:1255 EBOV evolution 1242:1255 We conclude that: 1) the common practice of rooting the phylogeny of EBOV between the first known outbreak in 1976 and the next outbreak in 1995 provides a misleading view of EBOV evolution that ignores the fact that there is a non-human EBOV host between outbreaks; 2) the N-terminus of GP1 may be constrained from evolving in response to the host immune system by the highly expressed, secreted glycoprotein, which is encoded by the same region of the GP gene; 3) although the mucin-like domain of GP1 is essential for EBOV in vivo, it evolves rapidly without losing its twin functions: providing O-linked glycosylation sites and a flexible surface. 27479005 4 40 gly glycoprotein 611:622 arg1 one 580:582 one 580:582 one 580:582 We have focused this study on the evolution of the EBOV glycoprotein gene (GP) because one of its products, the spike glycoprotein (GP1,2), is central to the host immune response and because it contains a large amount of the phylogenetic signal for this virus. 27479005 4 40 gly glycoprotein 611:622 arg1 products 591:598 its products 587:598 its products 587:598 We have focused this study on the evolution of the EBOV glycoprotein gene (GP) because one of its products, the spike glycoprotein (GP1,2), is central to the host immune response and because it contains a large amount of the phylogenetic signal for this virus. 27479005 4 40 gly glycoprotein 611:622 arg1 GP1,2 625:629 GP1,2 625:629 GP1,2 625:629 We have focused this study on the evolution of the EBOV glycoprotein gene (GP) because one of its products, the spike glycoprotein (GP1,2), is central to the host immune response and because it contains a large amount of the phylogenetic signal for this virus. 27479005 4 40 gly glycoprotein 611:622 arg1 glycoprotein 611:622 the spike glycoprotein 601:622 the spike glycoprotein (GP1,2) 601:630 We have focused this study on the evolution of the EBOV glycoprotein gene (GP) because one of its products, the spike glycoprotein (GP1,2), is central to the host immune response and because it contains a large amount of the phylogenetic signal for this virus. 27479005 7 41 theme mucin-like 1546:1555 arg1 essential 1574:1582 essential 1574:1582 essential 1574:1582 We conclude that: 1) the common practice of rooting the phylogeny of EBOV between the first known outbreak in 1976 and the next outbreak in 1995 provides a misleading view of EBOV evolution that ignores the fact that there is a non-human EBOV host between outbreaks; 2) the N-terminus of GP1 may be constrained from evolving in response to the host immune system by the highly expressed, secreted glycoprotein, which is encoded by the same region of the GP gene; 3) although the mucin-like domain of GP1 is essential for EBOV in vivo, it evolves rapidly without losing its twin functions: providing O-linked glycosylation sites and a flexible surface. 27479005 7 41 theme mucin-like 1546:1555 arg1 GP1 1567:1569 GP1 1567:1569 GP1 1567:1569 We conclude that: 1) the common practice of rooting the phylogeny of EBOV between the first known outbreak in 1976 and the next outbreak in 1995 provides a misleading view of EBOV evolution that ignores the fact that there is a non-human EBOV host between outbreaks; 2) the N-terminus of GP1 may be constrained from evolving in response to the host immune system by the highly expressed, secreted glycoprotein, which is encoded by the same region of the GP gene; 3) although the mucin-like domain of GP1 is essential for EBOV in vivo, it evolves rapidly without losing its twin functions: providing O-linked glycosylation sites and a flexible surface. 27479005 7 41 theme mucin-like 1546:1555 arg1 domain 1557:1562 the mucin-like domain 1542:1562 the mucin-like domain of GP1 1542:1569 We conclude that: 1) the common practice of rooting the phylogeny of EBOV between the first known outbreak in 1976 and the next outbreak in 1995 provides a misleading view of EBOV evolution that ignores the fact that there is a non-human EBOV host between outbreaks; 2) the N-terminus of GP1 may be constrained from evolving in response to the host immune system by the highly expressed, secreted glycoprotein, which is encoded by the same region of the GP gene; 3) although the mucin-like domain of GP1 is essential for EBOV in vivo, it evolves rapidly without losing its twin functions: providing O-linked glycosylation sites and a flexible surface. 27479005 2 42 theme sequencing 275:284 arg1 EBOV 299:302 EBOV 299:302 EBOV 299:302 There has been a considerable investment in sequencing Ebola virus (EBOV) isolates, and the results paint an important picture of how the virus has spread in western Africa. 27479005 2 42 theme sequencing 275:284 arg1 virus 292:296 sequencing Ebola virus 275:296 sequencing Ebola virus (EBOV) isolates 275:312 There has been a considerable investment in sequencing Ebola virus (EBOV) isolates, and the results paint an important picture of how the virus has spread in western Africa. 27479005 3 43 theme EBOV 405:408 arg1 evolution 410:418 EBOV evolution 405:418 EBOV evolution 405:418 EBOV evolution cannot be understood outside the context of previous outbreaks, however. 27479005 2 44 theme Ebola 286:290 arg1 EBOV 299:302 EBOV 299:302 EBOV 299:302 There has been a considerable investment in sequencing Ebola virus (EBOV) isolates, and the results paint an important picture of how the virus has spread in western Africa. 27479005 2 44 theme Ebola 286:290 arg1 virus 292:296 sequencing Ebola virus 275:296 sequencing Ebola virus (EBOV) isolates 275:312 There has been a considerable investment in sequencing Ebola virus (EBOV) isolates, and the results paint an important picture of how the virus has spread in western Africa. 27479005 3 45 theme outbreaks 473:481 arg1 context 453:459 the context 449:459 the context of previous outbreaks 449:481 EBOV evolution cannot be understood outside the context of previous outbreaks, however. 27479005 1 46 theme disease 96:102 arg1 outbreak 72:79 the recent devastating outbreak 49:79 the recent devastating outbreak of Ebola virus disease in western Africa 49:120 Since the recent devastating outbreak of Ebola virus disease in western Africa, there has been significant effort to understand the evolution of the deadly virus that caused the outbreak. 27479005 7 47 theme expressed 1444:1452 arg1 glycoprotein 1464:1475 the highly expressed, secreted glycoprotein 1433:1475 the highly expressed, secreted glycoprotein 1433:1475 We conclude that: 1) the common practice of rooting the phylogeny of EBOV between the first known outbreak in 1976 and the next outbreak in 1995 provides a misleading view of EBOV evolution that ignores the fact that there is a non-human EBOV host between outbreaks; 2) the N-terminus of GP1 may be constrained from evolving in response to the host immune system by the highly expressed, secreted glycoprotein, which is encoded by the same region of the GP gene; 3) although the mucin-like domain of GP1 is essential for EBOV in vivo, it evolves rapidly without losing its twin functions: providing O-linked glycosylation sites and a flexible surface. 27479005 4 48 theme gene 562:565 arg1 evolution 527:535 the evolution 523:535 the evolution of the EBOV glycoprotein gene (GP) 523:570 We have focused this study on the evolution of the EBOV glycoprotein gene (GP) because one of its products, the spike glycoprotein (GP1,2), is central to the host immune response and because it contains a large amount of the phylogenetic signal for this virus. 27479005 7 49 dep provides 1212:1219 arg1 essential 1574:1582 essential 1574:1582 essential 1574:1582 We conclude that: 1) the common practice of rooting the phylogeny of EBOV between the first known outbreak in 1976 and the next outbreak in 1995 provides a misleading view of EBOV evolution that ignores the fact that there is a non-human EBOV host between outbreaks; 2) the N-terminus of GP1 may be constrained from evolving in response to the host immune system by the highly expressed, secreted glycoprotein, which is encoded by the same region of the GP gene; 3) although the mucin-like domain of GP1 is essential for EBOV in vivo, it evolves rapidly without losing its twin functions: providing O-linked glycosylation sites and a flexible surface. 27479005 7 49 dep provides 1212:1219 arg1 although 1533:1540 although 1533:1540 although 1533:1540 We conclude that: 1) the common practice of rooting the phylogeny of EBOV between the first known outbreak in 1976 and the next outbreak in 1995 provides a misleading view of EBOV evolution that ignores the fact that there is a non-human EBOV host between outbreaks; 2) the N-terminus of GP1 may be constrained from evolving in response to the host immune system by the highly expressed, secreted glycoprotein, which is encoded by the same region of the GP gene; 3) although the mucin-like domain of GP1 is essential for EBOV in vivo, it evolves rapidly without losing its twin functions: providing O-linked glycosylation sites and a flexible surface. 27479005 7 49 dep provides 1212:1219 arg1 domain 1557:1562 the mucin-like domain 1542:1562 the mucin-like domain of GP1 1542:1569 We conclude that: 1) the common practice of rooting the phylogeny of EBOV between the first known outbreak in 1976 and the next outbreak in 1995 provides a misleading view of EBOV evolution that ignores the fact that there is a non-human EBOV host between outbreaks; 2) the N-terminus of GP1 may be constrained from evolving in response to the host immune system by the highly expressed, secreted glycoprotein, which is encoded by the same region of the GP gene; 3) although the mucin-like domain of GP1 is essential for EBOV in vivo, it evolves rapidly without losing its twin functions: providing O-linked glycosylation sites and a flexible surface. 27479005 7 49 dep provides 1212:1219 arg1 2 1334:1334 2 1334:1334 2 1334:1334 We conclude that: 1) the common practice of rooting the phylogeny of EBOV between the first known outbreak in 1976 and the next outbreak in 1995 provides a misleading view of EBOV evolution that ignores the fact that there is a non-human EBOV host between outbreaks; 2) the N-terminus of GP1 may be constrained from evolving in response to the host immune system by the highly expressed, secreted glycoprotein, which is encoded by the same region of the GP gene; 3) although the mucin-like domain of GP1 is essential for EBOV in vivo, it evolves rapidly without losing its twin functions: providing O-linked glycosylation sites and a flexible surface. 27479005 7 49 dep provides 1212:1219 arg1 1 1085:1085 1 1085:1085 1 1085:1085 We conclude that: 1) the common practice of rooting the phylogeny of EBOV between the first known outbreak in 1976 and the next outbreak in 1995 provides a misleading view of EBOV evolution that ignores the fact that there is a non-human EBOV host between outbreaks; 2) the N-terminus of GP1 may be constrained from evolving in response to the host immune system by the highly expressed, secreted glycoprotein, which is encoded by the same region of the GP gene; 3) although the mucin-like domain of GP1 is essential for EBOV in vivo, it evolves rapidly without losing its twin functions: providing O-linked glycosylation sites and a flexible surface. 27479005 7 49 dep provides 1212:1219 arg1 3 1530:1530 3 1530:1530 3 1530:1530 We conclude that: 1) the common practice of rooting the phylogeny of EBOV between the first known outbreak in 1976 and the next outbreak in 1995 provides a misleading view of EBOV evolution that ignores the fact that there is a non-human EBOV host between outbreaks; 2) the N-terminus of GP1 may be constrained from evolving in response to the host immune system by the highly expressed, secreted glycoprotein, which is encoded by the same region of the GP gene; 3) although the mucin-like domain of GP1 is essential for EBOV in vivo, it evolves rapidly without losing its twin functions: providing O-linked glycosylation sites and a flexible surface. 27479005 7 49 dep provides 1212:1219 arg1 GP1 1567:1569 GP1 1567:1569 GP1 1567:1569 We conclude that: 1) the common practice of rooting the phylogeny of EBOV between the first known outbreak in 1976 and the next outbreak in 1995 provides a misleading view of EBOV evolution that ignores the fact that there is a non-human EBOV host between outbreaks; 2) the N-terminus of GP1 may be constrained from evolving in response to the host immune system by the highly expressed, secreted glycoprotein, which is encoded by the same region of the GP gene; 3) although the mucin-like domain of GP1 is essential for EBOV in vivo, it evolves rapidly without losing its twin functions: providing O-linked glycosylation sites and a flexible surface. 27479005 7 49 dep provides 1212:1219 arg1 constrained 1366:1376 constrained 1366:1376 may be constrained from evolving in response to the host immune system by the highly expressed, secreted glycoprotein, which is encoded by the same region of the GP gene 1359:1527 We conclude that: 1) the common practice of rooting the phylogeny of EBOV between the first known outbreak in 1976 and the next outbreak in 1995 provides a misleading view of EBOV evolution that ignores the fact that there is a non-human EBOV host between outbreaks; 2) the N-terminus of GP1 may be constrained from evolving in response to the host immune system by the highly expressed, secreted glycoprotein, which is encoded by the same region of the GP gene; 3) although the mucin-like domain of GP1 is essential for EBOV in vivo, it evolves rapidly without losing its twin functions: providing O-linked glycosylation sites and a flexible surface. 27479005 7 50 from EBOV 1588:1591 arg1 vivo 1596:1599 vivo 1596:1599 vivo 1596:1599 We conclude that: 1) the common practice of rooting the phylogeny of EBOV between the first known outbreak in 1976 and the next outbreak in 1995 provides a misleading view of EBOV evolution that ignores the fact that there is a non-human EBOV host between outbreaks; 2) the N-terminus of GP1 may be constrained from evolving in response to the host immune system by the highly expressed, secreted glycoprotein, which is encoded by the same region of the GP gene; 3) although the mucin-like domain of GP1 is essential for EBOV in vivo, it evolves rapidly without losing its twin functions: providing O-linked glycosylation sites and a flexible surface. 27479005 4 51 theme large 698:702 arg1 signal 731:736 the phylogenetic signal 714:736 the phylogenetic signal for this virus 714:751 We have focused this study on the evolution of the EBOV glycoprotein gene (GP) because one of its products, the spike glycoprotein (GP1,2), is central to the host immune response and because it contains a large amount of the phylogenetic signal for this virus. 27479005 4 51 theme large 698:702 arg1 amount 704:709 a large amount 696:709 a large amount of the phylogenetic signal for this virus 696:751 We have focused this study on the evolution of the EBOV glycoprotein gene (GP) because one of its products, the spike glycoprotein (GP1,2), is central to the host immune response and because it contains a large amount of the phylogenetic signal for this virus. 27479005 6 52 theme positive 919:926 arg1 selection 928:936 positive selection 919:936 positive selection 919:936 We tested for positive selection and considered the placement of adaptive amino acid substitutions along the phylogeny and within the protein structure of GP1,2. 27479005 7 53 theme EBOV 1136:1139 arg1 phylogeny 1123:1131 the phylogeny 1119:1131 the phylogeny of EBOV 1119:1139 We conclude that: 1) the common practice of rooting the phylogeny of EBOV between the first known outbreak in 1976 and the next outbreak in 1995 provides a misleading view of EBOV evolution that ignores the fact that there is a non-human EBOV host between outbreaks; 2) the N-terminus of GP1 may be constrained from evolving in response to the host immune system by the highly expressed, secreted glycoprotein, which is encoded by the same region of the GP gene; 3) although the mucin-like domain of GP1 is essential for EBOV in vivo, it evolves rapidly without losing its twin functions: providing O-linked glycosylation sites and a flexible surface. 27479005 0 54 theme Virus 26:30 arg1 Evolution 32:40 Ebola Virus Evolution 20:40 Ebola Virus Evolution 20:40 New Perspectives on Ebola Virus Evolution. 27479005 7 55 theme host 1411:1414 arg1 system 1423:1428 the host immune system 1407:1428 the host immune system 1407:1428 We conclude that: 1) the common practice of rooting the phylogeny of EBOV between the first known outbreak in 1976 and the next outbreak in 1995 provides a misleading view of EBOV evolution that ignores the fact that there is a non-human EBOV host between outbreaks; 2) the N-terminus of GP1 may be constrained from evolving in response to the host immune system by the highly expressed, secreted glycoprotein, which is encoded by the same region of the GP gene; 3) although the mucin-like domain of GP1 is essential for EBOV in vivo, it evolves rapidly without losing its twin functions: providing O-linked glycosylation sites and a flexible surface. 27479005 7 56 theme misleading 1223:1232 arg1 view 1234:1237 a misleading view 1221:1237 a misleading view of EBOV evolution that ignores the fact that there is a non-human EBOV host between outbreaks 1221:1331 We conclude that: 1) the common practice of rooting the phylogeny of EBOV between the first known outbreak in 1976 and the next outbreak in 1995 provides a misleading view of EBOV evolution that ignores the fact that there is a non-human EBOV host between outbreaks; 2) the N-terminus of GP1 may be constrained from evolving in response to the host immune system by the highly expressed, secreted glycoprotein, which is encoded by the same region of the GP gene; 3) although the mucin-like domain of GP1 is essential for EBOV in vivo, it evolves rapidly without losing its twin functions: providing O-linked glycosylation sites and a flexible surface. 27479005 1 57 theme deadly 192:197 arg1 virus 199:203 the deadly virus 188:203 the deadly virus that caused the outbreak 188:228 Since the recent devastating outbreak of Ebola virus disease in western Africa, there has been significant effort to understand the evolution of the deadly virus that caused the outbreak. 27479005 7 58 theme immune 1416:1421 arg1 system 1423:1428 the host immune system 1407:1428 the host immune system 1407:1428 We conclude that: 1) the common practice of rooting the phylogeny of EBOV between the first known outbreak in 1976 and the next outbreak in 1995 provides a misleading view of EBOV evolution that ignores the fact that there is a non-human EBOV host between outbreaks; 2) the N-terminus of GP1 may be constrained from evolving in response to the host immune system by the highly expressed, secreted glycoprotein, which is encoded by the same region of the GP gene; 3) although the mucin-like domain of GP1 is essential for EBOV in vivo, it evolves rapidly without losing its twin functions: providing O-linked glycosylation sites and a flexible surface. 27479005 2 59 from paint 331:335 arg1 isolates 305:312 sequencing Ebola virus (EBOV) isolates 275:312 sequencing Ebola virus (EBOV) isolates 275:312 There has been a considerable investment in sequencing Ebola virus (EBOV) isolates, and the results paint an important picture of how the virus has spread in western Africa. 27479005 5 60 theme sequences 826:834 arg1 phylogeny 789:797 the maximum likelihood phylogeny 766:797 the maximum likelihood phylogeny of 96 nonredundant GP gene sequences representing each of the outbreaks since 1976 up to the end of 2014 766:902 We inferred the maximum likelihood phylogeny of 96 nonredundant GP gene sequences representing each of the outbreaks since 1976 up to the end of 2014. 27479005 7 61 theme EBOV 1305:1308 arg1 host 1310:1313 a non-human EBOV host 1293:1313 a non-human EBOV host between outbreaks 1293:1331 We conclude that: 1) the common practice of rooting the phylogeny of EBOV between the first known outbreak in 1976 and the next outbreak in 1995 provides a misleading view of EBOV evolution that ignores the fact that there is a non-human EBOV host between outbreaks; 2) the N-terminus of GP1 may be constrained from evolving in response to the host immune system by the highly expressed, secreted glycoprotein, which is encoded by the same region of the GP gene; 3) although the mucin-like domain of GP1 is essential for EBOV in vivo, it evolves rapidly without losing its twin functions: providing O-linked glycosylation sites and a flexible surface. 27479005 5 62 theme 2014 899:902 arg1 end 892:894 the end 888:894 the end of 2014 888:902 We inferred the maximum likelihood phylogeny of 96 nonredundant GP gene sequences representing each of the outbreaks since 1976 up to the end of 2014. 27479005 6 63 theme substitutions 990:1002 arg1 placement 957:965 the placement 953:965 the placement of adaptive amino acid substitutions along the phylogeny and within the protein structure of GP1,2 953:1064 We tested for positive selection and considered the placement of adaptive amino acid substitutions along the phylogeny and within the protein structure of GP1,2. 27479005 7 64 theme GP 1521:1522 arg1 gene 1524:1527 the GP gene 1517:1527 the GP gene 1517:1527 We conclude that: 1) the common practice of rooting the phylogeny of EBOV between the first known outbreak in 1976 and the next outbreak in 1995 provides a misleading view of EBOV evolution that ignores the fact that there is a non-human EBOV host between outbreaks; 2) the N-terminus of GP1 may be constrained from evolving in response to the host immune system by the highly expressed, secreted glycoprotein, which is encoded by the same region of the GP gene; 3) although the mucin-like domain of GP1 is essential for EBOV in vivo, it evolves rapidly without losing its twin functions: providing O-linked glycosylation sites and a flexible surface. 27479005 6 65 theme GP1,2 1060:1064 arg1 structure 1047:1055 the protein structure 1035:1055 the protein structure of GP1,2 1035:1064 We tested for positive selection and considered the placement of adaptive amino acid substitutions along the phylogeny and within the protein structure of GP1,2. 27479005 7 66 theme next 1190:1193 arg1 outbreak 1195:1202 the next outbreak 1186:1202 the next outbreak in 1995 1186:1210 We conclude that: 1) the common practice of rooting the phylogeny of EBOV between the first known outbreak in 1976 and the next outbreak in 1995 provides a misleading view of EBOV evolution that ignores the fact that there is a non-human EBOV host between outbreaks; 2) the N-terminus of GP1 may be constrained from evolving in response to the host immune system by the highly expressed, secreted glycoprotein, which is encoded by the same region of the GP gene; 3) although the mucin-like domain of GP1 is essential for EBOV in vivo, it evolves rapidly without losing its twin functions: providing O-linked glycosylation sites and a flexible surface. 27479005 7 67 theme evolution 1247:1255 arg1 view 1234:1237 a misleading view 1221:1237 a misleading view of EBOV evolution that ignores the fact that there is a non-human EBOV host between outbreaks 1221:1331 We conclude that: 1) the common practice of rooting the phylogeny of EBOV between the first known outbreak in 1976 and the next outbreak in 1995 provides a misleading view of EBOV evolution that ignores the fact that there is a non-human EBOV host between outbreaks; 2) the N-terminus of GP1 may be constrained from evolving in response to the host immune system by the highly expressed, secreted glycoprotein, which is encoded by the same region of the GP gene; 3) although the mucin-like domain of GP1 is essential for EBOV in vivo, it evolves rapidly without losing its twin functions: providing O-linked glycosylation sites and a flexible surface. 27479005 6 68 theme acid 985:988 arg1 substitutions 990:1002 adaptive amino acid substitutions 970:1002 adaptive amino acid substitutions 970:1002 We tested for positive selection and considered the placement of adaptive amino acid substitutions along the phylogeny and within the protein structure of GP1,2. 27479005 1 69 theme virus 90:94 arg1 disease 96:102 Ebola virus disease 84:102 Ebola virus disease 84:102 Since the recent devastating outbreak of Ebola virus disease in western Africa, there has been significant effort to understand the evolution of the deadly virus that caused the outbreak. 27479005 1 70 theme virus 199:203 arg1 evolution 175:183 the evolution 171:183 the evolution of the deadly virus that caused the outbreak 171:228 Since the recent devastating outbreak of Ebola virus disease in western Africa, there has been significant effort to understand the evolution of the deadly virus that caused the outbreak. 27479005 7 71 dep expressed 1444:1452 arg1 secreted 1455:1462 secreted 1455:1462 secreted 1455:1462 We conclude that: 1) the common practice of rooting the phylogeny of EBOV between the first known outbreak in 1976 and the next outbreak in 1995 provides a misleading view of EBOV evolution that ignores the fact that there is a non-human EBOV host between outbreaks; 2) the N-terminus of GP1 may be constrained from evolving in response to the host immune system by the highly expressed, secreted glycoprotein, which is encoded by the same region of the GP gene; 3) although the mucin-like domain of GP1 is essential for EBOV in vivo, it evolves rapidly without losing its twin functions: providing O-linked glycosylation sites and a flexible surface. 27479005 4 72 theme products 591:598 arg1 one 580:582 one 580:582 one 580:582 We have focused this study on the evolution of the EBOV glycoprotein gene (GP) because one of its products, the spike glycoprotein (GP1,2), is central to the host immune response and because it contains a large amount of the phylogenetic signal for this virus. 27479005 4 72 theme products 591:598 arg1 products 591:598 its products 587:598 its products 587:598 We have focused this study on the evolution of the EBOV glycoprotein gene (GP) because one of its products, the spike glycoprotein (GP1,2), is central to the host immune response and because it contains a large amount of the phylogenetic signal for this virus. 27479005 4 72 theme products 591:598 arg1 glycoprotein 611:622 the spike glycoprotein 601:622 the spike glycoprotein (GP1,2) 601:630 We have focused this study on the evolution of the EBOV glycoprotein gene (GP) because one of its products, the spike glycoprotein (GP1,2), is central to the host immune response and because it contains a large amount of the phylogenetic signal for this virus. 27479005 2 73 from investment 261:270 arg1 isolates 305:312 sequencing Ebola virus (EBOV) isolates 275:312 sequencing Ebola virus (EBOV) isolates 275:312 There has been a considerable investment in sequencing Ebola virus (EBOV) isolates, and the results paint an important picture of how the virus has spread in western Africa. 27479005 4 74 contain contains 687:694 arg1 it 684:685 it 684:685 it 684:685 We have focused this study on the evolution of the EBOV glycoprotein gene (GP) because one of its products, the spike glycoprotein (GP1,2), is central to the host immune response and because it contains a large amount of the phylogenetic signal for this virus. 27479005 4 74 contain contains 687:694 arg2 amount 704:709 a large amount 696:709 a large amount of the phylogenetic signal for this virus 696:751 We have focused this study on the evolution of the EBOV glycoprotein gene (GP) because one of its products, the spike glycoprotein (GP1,2), is central to the host immune response and because it contains a large amount of the phylogenetic signal for this virus. 27479005 4 74 contain contains 687:694 arg2 signal 731:736 the phylogenetic signal 714:736 the phylogenetic signal for this virus 714:751 We have focused this study on the evolution of the EBOV glycoprotein gene (GP) because one of its products, the spike glycoprotein (GP1,2), is central to the host immune response and because it contains a large amount of the phylogenetic signal for this virus. 27479005 7 75 from outbreak 1165:1172 arg1 outbreak 1195:1202 the next outbreak 1186:1202 the next outbreak in 1995 1186:1210 We conclude that: 1) the common practice of rooting the phylogeny of EBOV between the first known outbreak in 1976 and the next outbreak in 1995 provides a misleading view of EBOV evolution that ignores the fact that there is a non-human EBOV host between outbreaks; 2) the N-terminus of GP1 may be constrained from evolving in response to the host immune system by the highly expressed, secreted glycoprotein, which is encoded by the same region of the GP gene; 3) although the mucin-like domain of GP1 is essential for EBOV in vivo, it evolves rapidly without losing its twin functions: providing O-linked glycosylation sites and a flexible surface. 27479005 7 75 from outbreak 1165:1172 arg1 1976 1177:1180 1976 1177:1180 1976 1177:1180 We conclude that: 1) the common practice of rooting the phylogeny of EBOV between the first known outbreak in 1976 and the next outbreak in 1995 provides a misleading view of EBOV evolution that ignores the fact that there is a non-human EBOV host between outbreaks; 2) the N-terminus of GP1 may be constrained from evolving in response to the host immune system by the highly expressed, secreted glycoprotein, which is encoded by the same region of the GP gene; 3) although the mucin-like domain of GP1 is essential for EBOV in vivo, it evolves rapidly without losing its twin functions: providing O-linked glycosylation sites and a flexible surface. 27479005 6 76 theme adaptive 970:977 arg1 substitutions 990:1002 adaptive amino acid substitutions 970:1002 adaptive amino acid substitutions 970:1002 We tested for positive selection and considered the placement of adaptive amino acid substitutions along the phylogeny and within the protein structure of GP1,2. 27479005 6 77 theme protein 1039:1045 arg1 structure 1047:1055 the protein structure 1035:1055 the protein structure of GP1,2 1035:1064 We tested for positive selection and considered the placement of adaptive amino acid substitutions along the phylogeny and within the protein structure of GP1,2. 27479005 4 78 theme glycoprotein 549:560 arg1 GP 568:569 GP 568:569 GP 568:569 We have focused this study on the evolution of the EBOV glycoprotein gene (GP) because one of its products, the spike glycoprotein (GP1,2), is central to the host immune response and because it contains a large amount of the phylogenetic signal for this virus. 27479005 4 78 theme glycoprotein 549:560 arg1 gene 562:565 the EBOV glycoprotein gene 540:565 the EBOV glycoprotein gene (GP) 540:570 We have focused this study on the evolution of the EBOV glycoprotein gene (GP) because one of its products, the spike glycoprotein (GP1,2), is central to the host immune response and because it contains a large amount of the phylogenetic signal for this virus. 27479005 7 79 gly glycoprotein 1464:1475 arg1 glycoprotein 1464:1475 the highly expressed, secreted glycoprotein 1433:1475 the highly expressed, secreted glycoprotein 1433:1475 We conclude that: 1) the common practice of rooting the phylogeny of EBOV between the first known outbreak in 1976 and the next outbreak in 1995 provides a misleading view of EBOV evolution that ignores the fact that there is a non-human EBOV host between outbreaks; 2) the N-terminus of GP1 may be constrained from evolving in response to the host immune system by the highly expressed, secreted glycoprotein, which is encoded by the same region of the GP gene; 3) although the mucin-like domain of GP1 is essential for EBOV in vivo, it evolves rapidly without losing its twin functions: providing O-linked glycosylation sites and a flexible surface. 27479005 6 80 theme amino 979:983 arg1 substitutions 990:1002 adaptive amino acid substitutions 970:1002 adaptive amino acid substitutions 970:1002 We tested for positive selection and considered the placement of adaptive amino acid substitutions along the phylogeny and within the protein structure of GP1,2. 27479005 7 81 theme GP1 1567:1569 arg1 essential 1574:1582 essential 1574:1582 essential 1574:1582 We conclude that: 1) the common practice of rooting the phylogeny of EBOV between the first known outbreak in 1976 and the next outbreak in 1995 provides a misleading view of EBOV evolution that ignores the fact that there is a non-human EBOV host between outbreaks; 2) the N-terminus of GP1 may be constrained from evolving in response to the host immune system by the highly expressed, secreted glycoprotein, which is encoded by the same region of the GP gene; 3) although the mucin-like domain of GP1 is essential for EBOV in vivo, it evolves rapidly without losing its twin functions: providing O-linked glycosylation sites and a flexible surface. 27479005 7 81 theme GP1 1567:1569 arg1 GP1 1567:1569 GP1 1567:1569 GP1 1567:1569 We conclude that: 1) the common practice of rooting the phylogeny of EBOV between the first known outbreak in 1976 and the next outbreak in 1995 provides a misleading view of EBOV evolution that ignores the fact that there is a non-human EBOV host between outbreaks; 2) the N-terminus of GP1 may be constrained from evolving in response to the host immune system by the highly expressed, secreted glycoprotein, which is encoded by the same region of the GP gene; 3) although the mucin-like domain of GP1 is essential for EBOV in vivo, it evolves rapidly without losing its twin functions: providing O-linked glycosylation sites and a flexible surface. 27479005 7 81 theme GP1 1567:1569 arg1 domain 1557:1562 the mucin-like domain 1542:1562 the mucin-like domain of GP1 1542:1569 We conclude that: 1) the common practice of rooting the phylogeny of EBOV between the first known outbreak in 1976 and the next outbreak in 1995 provides a misleading view of EBOV evolution that ignores the fact that there is a non-human EBOV host between outbreaks; 2) the N-terminus of GP1 may be constrained from evolving in response to the host immune system by the highly expressed, secreted glycoprotein, which is encoded by the same region of the GP gene; 3) although the mucin-like domain of GP1 is essential for EBOV in vivo, it evolves rapidly without losing its twin functions: providing O-linked glycosylation sites and a flexible surface. 27479005 3 82 theme previous 464:471 arg1 outbreaks 473:481 previous outbreaks 464:481 previous outbreaks 464:481 EBOV evolution cannot be understood outside the context of previous outbreaks, however. 27479005 7 83 theme same 1502:1505 arg1 region 1507:1512 the same region 1498:1512 the same region of the GP gene 1498:1527 We conclude that: 1) the common practice of rooting the phylogeny of EBOV between the first known outbreak in 1976 and the next outbreak in 1995 provides a misleading view of EBOV evolution that ignores the fact that there is a non-human EBOV host between outbreaks; 2) the N-terminus of GP1 may be constrained from evolving in response to the host immune system by the highly expressed, secreted glycoprotein, which is encoded by the same region of the GP gene; 3) although the mucin-like domain of GP1 is essential for EBOV in vivo, it evolves rapidly without losing its twin functions: providing O-linked glycosylation sites and a flexible surface. 27479005 4 84 theme EBOV 544:547 arg1 GP 568:569 GP 568:569 GP 568:569 We have focused this study on the evolution of the EBOV glycoprotein gene (GP) because one of its products, the spike glycoprotein (GP1,2), is central to the host immune response and because it contains a large amount of the phylogenetic signal for this virus. 27479005 4 84 theme EBOV 544:547 arg1 gene 562:565 the EBOV glycoprotein gene 540:565 the EBOV glycoprotein gene (GP) 540:570 We have focused this study on the evolution of the EBOV glycoprotein gene (GP) because one of its products, the spike glycoprotein (GP1,2), is central to the host immune response and because it contains a large amount of the phylogenetic signal for this virus. 25244057 7 0 theme large 1313:1317 arg1 carcinoma 1324:1332 large cell carcinoma 1313:1332 large cell carcinoma 1313:1332 The glycosylation profiling of fibronectin indicated that the peanut agglutinin (PNA) signal appeared to differentiate two NSCLC types, adenocarcinoma and large cell carcinoma, whereas the protein expression level was similar between these types. 25244057 7 0 theme large 1313:1317 arg1 types 1287:1291 two NSCLC types 1277:1291 two NSCLC types 1277:1291 The glycosylation profiling of fibronectin indicated that the peanut agglutinin (PNA) signal appeared to differentiate two NSCLC types, adenocarcinoma and large cell carcinoma, whereas the protein expression level was similar between these types. 25244057 2 1 theme lung 391:394 arg1 tissue 403:408 lung cancer tissue 391:408 lung cancer tissue 391:408 Thus, we focused on discovering glycobiomarker candidates to classify the types of lung cancer tissue. 25244057 1 2 theme prognosis 297:305 arg1 prediction 275:284 the prediction 271:284 the prediction of patient prognosis 271:305 Histopathological classification of lung cancer has important implications in the application of clinical practice guidelines and the prediction of patient prognosis. 25244057 1 2 theme prognosis 297:305 arg1 application 223:233 the application 219:233 the application of clinical practice guidelines 219:265 Histopathological classification of lung cancer has important implications in the application of clinical practice guidelines and the prediction of patient prognosis. 25244057 8 3 theme concurrent 1452:1461 arg1 applicable 1496:1505 applicable 1496:1505 applicable 1496:1505 Our glycoproteomics approach together with the concurrent use of an antibody and lectin is applicable to the quantitative and qualitative monitoring of variations in glycosylation of fibronectin specific to certain types of lung cancer tissue. 25244057 8 3 theme concurrent 1452:1461 arg1 use 1463:1465 the concurrent use 1448:1465 Our glycoproteomics approach together with the concurrent use of an antibody and lectin 1405:1491 Our glycoproteomics approach together with the concurrent use of an antibody and lectin is applicable to the quantitative and qualitative monitoring of variations in glycosylation of fibronectin specific to certain types of lung cancer tissue. 25244057 7 4 theme fibronectin 1189:1199 arg1 profiling 1176:1184 The glycosylation profiling 1158:1184 The glycosylation profiling of fibronectin 1158:1199 The glycosylation profiling of fibronectin indicated that the peanut agglutinin (PNA) signal appeared to differentiate two NSCLC types, adenocarcinoma and large cell carcinoma, whereas the protein expression level was similar between these types. 25244057 4 5 theme glycoproteins 882:894 arg1 glycoforms 868:877 NSCLC-specific glycoforms 853:877 NSCLC-specific glycoforms of glycoproteins 853:894 LC-MS-based analysis was performed for the comprehensive identification of glycoproteins and N-linked glycosylation sites using lectin affinity capture of NSCLC-specific glycoforms of glycoproteins. 25244057 3 6 theme hybrid 563:568 arg1 lectin 570:575 Hippeastrum hybrid lectin 551:575 Hippeastrum hybrid lectin (HHL) 551:581 First, we performed lectin microarray analysis of lung cancer tissue specimens and cell lines and identified Aleuria aurantia lectin (AAL), Hippeastrum hybrid lectin (HHL), and Concanavalia ensiformis agglutinin (ConA) as lectin probes specific to non-small cell lung carcinoma (NSCLC). 25244057 3 6 theme hybrid 563:568 arg1 agglutinin 612:621 Concanavalia ensiformis agglutinin 588:621 Concanavalia ensiformis agglutinin (ConA) 588:628 First, we performed lectin microarray analysis of lung cancer tissue specimens and cell lines and identified Aleuria aurantia lectin (AAL), Hippeastrum hybrid lectin (HHL), and Concanavalia ensiformis agglutinin (ConA) as lectin probes specific to non-small cell lung carcinoma (NSCLC). 25244057 3 6 theme hybrid 563:568 arg1 probes 640:645 lectin probes 633:645 lectin probes specific to non-small cell lung carcinoma (NSCLC) 633:695 First, we performed lectin microarray analysis of lung cancer tissue specimens and cell lines and identified Aleuria aurantia lectin (AAL), Hippeastrum hybrid lectin (HHL), and Concanavalia ensiformis agglutinin (ConA) as lectin probes specific to non-small cell lung carcinoma (NSCLC). 25244057 3 6 theme hybrid 563:568 arg1 lectin 537:542 Aleuria aurantia lectin 520:542 Aleuria aurantia lectin (AAL) 520:548 First, we performed lectin microarray analysis of lung cancer tissue specimens and cell lines and identified Aleuria aurantia lectin (AAL), Hippeastrum hybrid lectin (HHL), and Concanavalia ensiformis agglutinin (ConA) as lectin probes specific to non-small cell lung carcinoma (NSCLC). 25244057 3 6 theme hybrid 563:568 arg1 HHL 578:580 HHL 578:580 HHL 578:580 First, we performed lectin microarray analysis of lung cancer tissue specimens and cell lines and identified Aleuria aurantia lectin (AAL), Hippeastrum hybrid lectin (HHL), and Concanavalia ensiformis agglutinin (ConA) as lectin probes specific to non-small cell lung carcinoma (NSCLC). 25244057 5 7 theme AAL-bound 927:935 arg1 glycoproteins 937:949 1092 AAL-bound glycoproteins 922:949 1092 AAL-bound glycoproteins (316 gene symbols) 922:968 This analysis identified 1092 AAL-bound glycoproteins (316 gene symbols) and 948 HHL/ConA-bound glycoproteins (279 gene symbols). 25244057 5 7 theme AAL-bound 927:935 arg1 symbols 961:967 316 gene symbols 952:967 316 gene symbols 952:967 This analysis identified 1092 AAL-bound glycoproteins (316 gene symbols) and 948 HHL/ConA-bound glycoproteins (279 gene symbols). 25244057 4 8 gly glycoproteins 882:894 arg1 glycoproteins 882:894 glycoproteins 882:894 glycoproteins 882:894 LC-MS-based analysis was performed for the comprehensive identification of glycoproteins and N-linked glycosylation sites using lectin affinity capture of NSCLC-specific glycoforms of glycoproteins. 25244057 8 9 theme quantitative 1514:1525 arg1 monitoring 1543:1552 the quantitative and qualitative monitoring 1510:1552 the quantitative and qualitative monitoring of variations in glycosylation of fibronectin specific to certain types of lung cancer tissue 1510:1646 Our glycoproteomics approach together with the concurrent use of an antibody and lectin is applicable to the quantitative and qualitative monitoring of variations in glycosylation of fibronectin specific to certain types of lung cancer tissue. 25244057 1 10 theme guidelines 256:265 arg1 prediction 275:284 the prediction 271:284 the prediction of patient prognosis 271:305 Histopathological classification of lung cancer has important implications in the application of clinical practice guidelines and the prediction of patient prognosis. 25244057 1 10 theme guidelines 256:265 arg1 application 223:233 the application 219:233 the application of clinical practice guidelines 219:265 Histopathological classification of lung cancer has important implications in the application of clinical practice guidelines and the prediction of patient prognosis. 25244057 8 11 theme qualitative 1531:1541 arg1 monitoring 1543:1552 the quantitative and qualitative monitoring 1510:1552 the quantitative and qualitative monitoring of variations in glycosylation of fibronectin specific to certain types of lung cancer tissue 1510:1646 Our glycoproteomics approach together with the concurrent use of an antibody and lectin is applicable to the quantitative and qualitative monitoring of variations in glycosylation of fibronectin specific to certain types of lung cancer tissue. 25244057 3 12 theme ensiformis 601:610 arg1 agglutinin 612:621 Concanavalia ensiformis agglutinin 588:621 Concanavalia ensiformis agglutinin (ConA) 588:628 First, we performed lectin microarray analysis of lung cancer tissue specimens and cell lines and identified Aleuria aurantia lectin (AAL), Hippeastrum hybrid lectin (HHL), and Concanavalia ensiformis agglutinin (ConA) as lectin probes specific to non-small cell lung carcinoma (NSCLC). 25244057 3 12 theme ensiformis 601:610 arg1 lectin 570:575 Hippeastrum hybrid lectin 551:575 Hippeastrum hybrid lectin (HHL) 551:581 First, we performed lectin microarray analysis of lung cancer tissue specimens and cell lines and identified Aleuria aurantia lectin (AAL), Hippeastrum hybrid lectin (HHL), and Concanavalia ensiformis agglutinin (ConA) as lectin probes specific to non-small cell lung carcinoma (NSCLC). 25244057 3 12 theme ensiformis 601:610 arg1 probes 640:645 lectin probes 633:645 lectin probes specific to non-small cell lung carcinoma (NSCLC) 633:695 First, we performed lectin microarray analysis of lung cancer tissue specimens and cell lines and identified Aleuria aurantia lectin (AAL), Hippeastrum hybrid lectin (HHL), and Concanavalia ensiformis agglutinin (ConA) as lectin probes specific to non-small cell lung carcinoma (NSCLC). 25244057 3 12 theme ensiformis 601:610 arg1 lectin 537:542 Aleuria aurantia lectin 520:542 Aleuria aurantia lectin (AAL) 520:548 First, we performed lectin microarray analysis of lung cancer tissue specimens and cell lines and identified Aleuria aurantia lectin (AAL), Hippeastrum hybrid lectin (HHL), and Concanavalia ensiformis agglutinin (ConA) as lectin probes specific to non-small cell lung carcinoma (NSCLC). 25244057 3 12 theme ensiformis 601:610 arg1 ConA 624:627 ConA 624:627 ConA 624:627 First, we performed lectin microarray analysis of lung cancer tissue specimens and cell lines and identified Aleuria aurantia lectin (AAL), Hippeastrum hybrid lectin (HHL), and Concanavalia ensiformis agglutinin (ConA) as lectin probes specific to non-small cell lung carcinoma (NSCLC). 25244057 1 13 theme Histopathological 141:157 arg1 classification 159:172 Histopathological classification 141:172 Histopathological classification of lung cancer 141:187 Histopathological classification of lung cancer has important implications in the application of clinical practice guidelines and the prediction of patient prognosis. 25244057 3 14 theme lectin 633:638 arg1 agglutinin 612:621 Concanavalia ensiformis agglutinin 588:621 Concanavalia ensiformis agglutinin (ConA) 588:628 First, we performed lectin microarray analysis of lung cancer tissue specimens and cell lines and identified Aleuria aurantia lectin (AAL), Hippeastrum hybrid lectin (HHL), and Concanavalia ensiformis agglutinin (ConA) as lectin probes specific to non-small cell lung carcinoma (NSCLC). 25244057 3 14 theme lectin 633:638 arg1 lectin 570:575 Hippeastrum hybrid lectin 551:575 Hippeastrum hybrid lectin (HHL) 551:581 First, we performed lectin microarray analysis of lung cancer tissue specimens and cell lines and identified Aleuria aurantia lectin (AAL), Hippeastrum hybrid lectin (HHL), and Concanavalia ensiformis agglutinin (ConA) as lectin probes specific to non-small cell lung carcinoma (NSCLC). 25244057 3 14 theme lectin 633:638 arg1 probes 640:645 lectin probes 633:645 lectin probes specific to non-small cell lung carcinoma (NSCLC) 633:695 First, we performed lectin microarray analysis of lung cancer tissue specimens and cell lines and identified Aleuria aurantia lectin (AAL), Hippeastrum hybrid lectin (HHL), and Concanavalia ensiformis agglutinin (ConA) as lectin probes specific to non-small cell lung carcinoma (NSCLC). 25244057 3 14 theme lectin 633:638 arg1 lectin 537:542 Aleuria aurantia lectin 520:542 Aleuria aurantia lectin (AAL) 520:548 First, we performed lectin microarray analysis of lung cancer tissue specimens and cell lines and identified Aleuria aurantia lectin (AAL), Hippeastrum hybrid lectin (HHL), and Concanavalia ensiformis agglutinin (ConA) as lectin probes specific to non-small cell lung carcinoma (NSCLC). 25244057 6 15 theme lung 1080:1083 arg1 lines 1097:1101 15 lung cancer cell lines 1077:1101 15 lung cancer cell lines 1077:1101 The lectin microarray-assisted verification using 15 lung cancer cell lines revealed the NSCLC-specific expression of fibronectin. 25244057 0 16 theme tissue 80:85 arg1 classification 92:105 tissue type classification 80:105 tissue type classification of non-small cell lung carcinoma 80:138 Glycoproteomics approach for identifying Glycobiomarker candidate molecules for tissue type classification of non-small cell lung carcinoma. 25244057 1 17 theme cancer 182:187 arg1 classification 159:172 Histopathological classification 141:172 Histopathological classification of lung cancer 141:187 Histopathological classification of lung cancer has important implications in the application of clinical practice guidelines and the prediction of patient prognosis. 25244057 4 18 theme LC-MS-based 698:708 arg1 analysis 710:717 LC-MS-based analysis 698:717 LC-MS-based analysis 698:717 LC-MS-based analysis was performed for the comprehensive identification of glycoproteins and N-linked glycosylation sites using lectin affinity capture of NSCLC-specific glycoforms of glycoproteins. 25244057 4 19 gly glycosylation 800:812 arg2 sites 814:818 N-linked glycosylation sites 791:818 N-linked glycosylation sites 791:818 LC-MS-based analysis was performed for the comprehensive identification of glycoproteins and N-linked glycosylation sites using lectin affinity capture of NSCLC-specific glycoforms of glycoproteins. 25244057 1 20 theme important 193:201 arg1 implications 203:214 important implications 193:214 important implications 193:214 Histopathological classification of lung cancer has important implications in the application of clinical practice guidelines and the prediction of patient prognosis. 25244057 6 21 theme microarray-assisted 1038:1056 arg1 verification 1058:1069 The lectin microarray-assisted verification 1027:1069 The lectin microarray-assisted verification using 15 lung cancer cell lines 1027:1101 The lectin microarray-assisted verification using 15 lung cancer cell lines revealed the NSCLC-specific expression of fibronectin. 25244057 5 22 gly glycoproteins 993:1005 arg1 symbols 1017:1023 279 gene symbols 1008:1023 279 gene symbols 1008:1023 This analysis identified 1092 AAL-bound glycoproteins (316 gene symbols) and 948 HHL/ConA-bound glycoproteins (279 gene symbols). 25244057 5 22 gly glycoproteins 993:1005 arg1 glycoproteins 993:1005 948 HHL/ConA-bound glycoproteins 974:1005 948 HHL/ConA-bound glycoproteins (279 gene symbols) 974:1024 This analysis identified 1092 AAL-bound glycoproteins (316 gene symbols) and 948 HHL/ConA-bound glycoproteins (279 gene symbols). 25244057 8 23 theme specific 1600:1607 arg1 fibronectin 1588:1598 fibronectin 1588:1598 fibronectin specific to certain types of lung cancer tissue 1588:1646 Our glycoproteomics approach together with the concurrent use of an antibody and lectin is applicable to the quantitative and qualitative monitoring of variations in glycosylation of fibronectin specific to certain types of lung cancer tissue. 25244057 0 24 theme non-small 110:118 arg1 carcinoma 130:138 non-small cell lung carcinoma 110:138 non-small cell lung carcinoma 110:138 Glycoproteomics approach for identifying Glycobiomarker candidate molecules for tissue type classification of non-small cell lung carcinoma. 25244057 8 25 theme certain 1612:1618 arg1 types 1620:1624 certain types 1612:1624 certain types of lung cancer tissue 1612:1646 Our glycoproteomics approach together with the concurrent use of an antibody and lectin is applicable to the quantitative and qualitative monitoring of variations in glycosylation of fibronectin specific to certain types of lung cancer tissue. 25244057 4 26 theme glycosylation 800:812 arg1 sites 814:818 N-linked glycosylation sites 791:818 N-linked glycosylation sites 791:818 LC-MS-based analysis was performed for the comprehensive identification of glycoproteins and N-linked glycosylation sites using lectin affinity capture of NSCLC-specific glycoforms of glycoproteins. 25244057 3 27 theme tissue 473:478 arg1 specimens 480:488 tissue specimens 473:488 tissue specimens 473:488 First, we performed lectin microarray analysis of lung cancer tissue specimens and cell lines and identified Aleuria aurantia lectin (AAL), Hippeastrum hybrid lectin (HHL), and Concanavalia ensiformis agglutinin (ConA) as lectin probes specific to non-small cell lung carcinoma (NSCLC). 25244057 0 28 theme lung 125:128 arg1 carcinoma 130:138 non-small cell lung carcinoma 110:138 non-small cell lung carcinoma 110:138 Glycoproteomics approach for identifying Glycobiomarker candidate molecules for tissue type classification of non-small cell lung carcinoma. 25244057 0 29 theme candidate 56:64 arg1 molecules 66:74 Glycobiomarker candidate molecules 41:74 Glycobiomarker candidate molecules for tissue type classification of non-small cell lung carcinoma 41:138 Glycoproteomics approach for identifying Glycobiomarker candidate molecules for tissue type classification of non-small cell lung carcinoma. 25244057 0 30 theme type 87:90 arg1 classification 92:105 tissue type classification 80:105 tissue type classification of non-small cell lung carcinoma 80:138 Glycoproteomics approach for identifying Glycobiomarker candidate molecules for tissue type classification of non-small cell lung carcinoma. 25244057 4 31 theme comprehensive 741:753 arg1 identification 755:768 the comprehensive identification 737:768 the comprehensive identification of glycoproteins and N-linked glycosylation sites 737:818 LC-MS-based analysis was performed for the comprehensive identification of glycoproteins and N-linked glycosylation sites using lectin affinity capture of NSCLC-specific glycoforms of glycoproteins. 25244057 3 32 theme lung 461:464 arg1 cancer 466:471 lung cancer tissue specimens and cell lines 461:503 cancer 466:471 First, we performed lectin microarray analysis of lung cancer tissue specimens and cell lines and identified Aleuria aurantia lectin (AAL), Hippeastrum hybrid lectin (HHL), and Concanavalia ensiformis agglutinin (ConA) as lectin probes specific to non-small cell lung carcinoma (NSCLC). 25244057 6 33 theme NSCLC-specific 1116:1129 arg1 expression 1131:1140 the NSCLC-specific expression 1112:1140 the NSCLC-specific expression of fibronectin 1112:1155 The lectin microarray-assisted verification using 15 lung cancer cell lines revealed the NSCLC-specific expression of fibronectin. 25244057 8 34 theme cancer 1634:1639 arg1 tissue 1641:1646 lung cancer tissue 1629:1646 lung cancer tissue 1629:1646 Our glycoproteomics approach together with the concurrent use of an antibody and lectin is applicable to the quantitative and qualitative monitoring of variations in glycosylation of fibronectin specific to certain types of lung cancer tissue. 25244057 3 35 theme lines 499:503 arg1 analysis 449:456 lectin microarray analysis 431:456 lectin microarray analysis of lung cancer tissue specimens and cell lines 431:503 First, we performed lectin microarray analysis of lung cancer tissue specimens and cell lines and identified Aleuria aurantia lectin (AAL), Hippeastrum hybrid lectin (HHL), and Concanavalia ensiformis agglutinin (ConA) as lectin probes specific to non-small cell lung carcinoma (NSCLC). 25244057 4 36 gly glycoforms 868:877 arg1 glycoproteins 882:894 glycoproteins 882:894 glycoproteins 882:894 LC-MS-based analysis was performed for the comprehensive identification of glycoproteins and N-linked glycosylation sites using lectin affinity capture of NSCLC-specific glycoforms of glycoproteins. 25244057 3 37 theme non-small 659:667 arg1 NSCLC 690:694 NSCLC 690:694 NSCLC 690:694 First, we performed lectin microarray analysis of lung cancer tissue specimens and cell lines and identified Aleuria aurantia lectin (AAL), Hippeastrum hybrid lectin (HHL), and Concanavalia ensiformis agglutinin (ConA) as lectin probes specific to non-small cell lung carcinoma (NSCLC). 25244057 3 37 theme non-small 659:667 arg1 carcinoma 679:687 non-small cell lung carcinoma 659:687 non-small cell lung carcinoma (NSCLC) 659:695 First, we performed lectin microarray analysis of lung cancer tissue specimens and cell lines and identified Aleuria aurantia lectin (AAL), Hippeastrum hybrid lectin (HHL), and Concanavalia ensiformis agglutinin (ConA) as lectin probes specific to non-small cell lung carcinoma (NSCLC). 25244057 8 38 theme antibody 1473:1480 arg1 applicable 1496:1505 applicable 1496:1505 applicable 1496:1505 Our glycoproteomics approach together with the concurrent use of an antibody and lectin is applicable to the quantitative and qualitative monitoring of variations in glycosylation of fibronectin specific to certain types of lung cancer tissue. 25244057 8 38 theme antibody 1473:1480 arg1 use 1463:1465 the concurrent use 1448:1465 Our glycoproteomics approach together with the concurrent use of an antibody and lectin 1405:1491 Our glycoproteomics approach together with the concurrent use of an antibody and lectin is applicable to the quantitative and qualitative monitoring of variations in glycosylation of fibronectin specific to certain types of lung cancer tissue. 25244057 0 39 theme Glycobiomarker 41:54 arg1 molecules 66:74 Glycobiomarker candidate molecules 41:74 Glycobiomarker candidate molecules for tissue type classification of non-small cell lung carcinoma 41:138 Glycoproteomics approach for identifying Glycobiomarker candidate molecules for tissue type classification of non-small cell lung carcinoma. 25244057 3 40 dep cancer 466:471 arg1 specimens 480:488 tissue specimens 473:488 tissue specimens 473:488 First, we performed lectin microarray analysis of lung cancer tissue specimens and cell lines and identified Aleuria aurantia lectin (AAL), Hippeastrum hybrid lectin (HHL), and Concanavalia ensiformis agglutinin (ConA) as lectin probes specific to non-small cell lung carcinoma (NSCLC). 25244057 6 41 theme cell 1092:1095 arg1 lines 1097:1101 15 lung cancer cell lines 1077:1101 15 lung cancer cell lines 1077:1101 The lectin microarray-assisted verification using 15 lung cancer cell lines revealed the NSCLC-specific expression of fibronectin. 25244057 3 42 theme lectin 431:436 arg1 analysis 449:456 lectin microarray analysis 431:456 lectin microarray analysis of lung cancer tissue specimens and cell lines 431:503 First, we performed lectin microarray analysis of lung cancer tissue specimens and cell lines and identified Aleuria aurantia lectin (AAL), Hippeastrum hybrid lectin (HHL), and Concanavalia ensiformis agglutinin (ConA) as lectin probes specific to non-small cell lung carcinoma (NSCLC). 25244057 3 43 theme specific 647:654 arg1 agglutinin 612:621 Concanavalia ensiformis agglutinin 588:621 Concanavalia ensiformis agglutinin (ConA) 588:628 First, we performed lectin microarray analysis of lung cancer tissue specimens and cell lines and identified Aleuria aurantia lectin (AAL), Hippeastrum hybrid lectin (HHL), and Concanavalia ensiformis agglutinin (ConA) as lectin probes specific to non-small cell lung carcinoma (NSCLC). 25244057 3 43 theme specific 647:654 arg1 lectin 570:575 Hippeastrum hybrid lectin 551:575 Hippeastrum hybrid lectin (HHL) 551:581 First, we performed lectin microarray analysis of lung cancer tissue specimens and cell lines and identified Aleuria aurantia lectin (AAL), Hippeastrum hybrid lectin (HHL), and Concanavalia ensiformis agglutinin (ConA) as lectin probes specific to non-small cell lung carcinoma (NSCLC). 25244057 3 43 theme specific 647:654 arg1 probes 640:645 lectin probes 633:645 lectin probes specific to non-small cell lung carcinoma (NSCLC) 633:695 First, we performed lectin microarray analysis of lung cancer tissue specimens and cell lines and identified Aleuria aurantia lectin (AAL), Hippeastrum hybrid lectin (HHL), and Concanavalia ensiformis agglutinin (ConA) as lectin probes specific to non-small cell lung carcinoma (NSCLC). 25244057 3 43 theme specific 647:654 arg1 lectin 537:542 Aleuria aurantia lectin 520:542 Aleuria aurantia lectin (AAL) 520:548 First, we performed lectin microarray analysis of lung cancer tissue specimens and cell lines and identified Aleuria aurantia lectin (AAL), Hippeastrum hybrid lectin (HHL), and Concanavalia ensiformis agglutinin (ConA) as lectin probes specific to non-small cell lung carcinoma (NSCLC). 25244057 4 44 theme glycoforms 868:877 arg1 capture 842:848 lectin affinity capture 826:848 lectin affinity capture of NSCLC-specific glycoforms of glycoproteins 826:894 LC-MS-based analysis was performed for the comprehensive identification of glycoproteins and N-linked glycosylation sites using lectin affinity capture of NSCLC-specific glycoforms of glycoproteins. 25244057 3 45 theme aurantia 528:535 arg1 agglutinin 612:621 Concanavalia ensiformis agglutinin 588:621 Concanavalia ensiformis agglutinin (ConA) 588:628 First, we performed lectin microarray analysis of lung cancer tissue specimens and cell lines and identified Aleuria aurantia lectin (AAL), Hippeastrum hybrid lectin (HHL), and Concanavalia ensiformis agglutinin (ConA) as lectin probes specific to non-small cell lung carcinoma (NSCLC). 25244057 3 45 theme aurantia 528:535 arg1 AAL 545:547 AAL 545:547 AAL 545:547 First, we performed lectin microarray analysis of lung cancer tissue specimens and cell lines and identified Aleuria aurantia lectin (AAL), Hippeastrum hybrid lectin (HHL), and Concanavalia ensiformis agglutinin (ConA) as lectin probes specific to non-small cell lung carcinoma (NSCLC). 25244057 3 45 theme aurantia 528:535 arg1 probes 640:645 lectin probes 633:645 lectin probes specific to non-small cell lung carcinoma (NSCLC) 633:695 First, we performed lectin microarray analysis of lung cancer tissue specimens and cell lines and identified Aleuria aurantia lectin (AAL), Hippeastrum hybrid lectin (HHL), and Concanavalia ensiformis agglutinin (ConA) as lectin probes specific to non-small cell lung carcinoma (NSCLC). 25244057 3 45 theme aurantia 528:535 arg1 lectin 537:542 Aleuria aurantia lectin 520:542 Aleuria aurantia lectin (AAL) 520:548 First, we performed lectin microarray analysis of lung cancer tissue specimens and cell lines and identified Aleuria aurantia lectin (AAL), Hippeastrum hybrid lectin (HHL), and Concanavalia ensiformis agglutinin (ConA) as lectin probes specific to non-small cell lung carcinoma (NSCLC). 25244057 3 45 theme aurantia 528:535 arg1 lectin 570:575 Hippeastrum hybrid lectin 551:575 Hippeastrum hybrid lectin (HHL) 551:581 First, we performed lectin microarray analysis of lung cancer tissue specimens and cell lines and identified Aleuria aurantia lectin (AAL), Hippeastrum hybrid lectin (HHL), and Concanavalia ensiformis agglutinin (ConA) as lectin probes specific to non-small cell lung carcinoma (NSCLC). 25244057 7 46 theme peanut 1220:1225 arg1 agglutinin 1227:1236 the peanut agglutinin 1216:1236 the peanut agglutinin (PNA) signal 1216:1249 The glycosylation profiling of fibronectin indicated that the peanut agglutinin (PNA) signal appeared to differentiate two NSCLC types, adenocarcinoma and large cell carcinoma, whereas the protein expression level was similar between these types. 25244057 7 46 theme peanut 1220:1225 arg1 PNA 1239:1241 PNA 1239:1241 PNA 1239:1241 The glycosylation profiling of fibronectin indicated that the peanut agglutinin (PNA) signal appeared to differentiate two NSCLC types, adenocarcinoma and large cell carcinoma, whereas the protein expression level was similar between these types. 25244057 7 47 theme expression 1355:1364 arg1 similar 1376:1382 similar 1376:1382 similar 1376:1382 The glycosylation profiling of fibronectin indicated that the peanut agglutinin (PNA) signal appeared to differentiate two NSCLC types, adenocarcinoma and large cell carcinoma, whereas the protein expression level was similar between these types. 25244057 7 47 theme expression 1355:1364 arg1 level 1366:1370 the protein expression level 1343:1370 the protein expression level 1343:1370 The glycosylation profiling of fibronectin indicated that the peanut agglutinin (PNA) signal appeared to differentiate two NSCLC types, adenocarcinoma and large cell carcinoma, whereas the protein expression level was similar between these types. 25244057 3 48 theme lung 674:677 arg1 NSCLC 690:694 NSCLC 690:694 NSCLC 690:694 First, we performed lectin microarray analysis of lung cancer tissue specimens and cell lines and identified Aleuria aurantia lectin (AAL), Hippeastrum hybrid lectin (HHL), and Concanavalia ensiformis agglutinin (ConA) as lectin probes specific to non-small cell lung carcinoma (NSCLC). 25244057 3 48 theme lung 674:677 arg1 carcinoma 679:687 non-small cell lung carcinoma 659:687 non-small cell lung carcinoma (NSCLC) 659:695 First, we performed lectin microarray analysis of lung cancer tissue specimens and cell lines and identified Aleuria aurantia lectin (AAL), Hippeastrum hybrid lectin (HHL), and Concanavalia ensiformis agglutinin (ConA) as lectin probes specific to non-small cell lung carcinoma (NSCLC). 25244057 4 49 theme affinity 833:840 arg1 capture 842:848 lectin affinity capture 826:848 lectin affinity capture of NSCLC-specific glycoforms of glycoproteins 826:894 LC-MS-based analysis was performed for the comprehensive identification of glycoproteins and N-linked glycosylation sites using lectin affinity capture of NSCLC-specific glycoforms of glycoproteins. 25244057 2 50 theme cancer 396:401 arg1 tissue 403:408 lung cancer tissue 391:408 lung cancer tissue 391:408 Thus, we focused on discovering glycobiomarker candidates to classify the types of lung cancer tissue. 25244057 1 51 theme patient 289:295 arg1 prognosis 297:305 patient prognosis 289:305 patient prognosis 289:305 Histopathological classification of lung cancer has important implications in the application of clinical practice guidelines and the prediction of patient prognosis. 25244057 7 52 theme cell 1319:1322 arg1 carcinoma 1324:1332 large cell carcinoma 1313:1332 large cell carcinoma 1313:1332 The glycosylation profiling of fibronectin indicated that the peanut agglutinin (PNA) signal appeared to differentiate two NSCLC types, adenocarcinoma and large cell carcinoma, whereas the protein expression level was similar between these types. 25244057 7 52 theme cell 1319:1322 arg1 types 1287:1291 two NSCLC types 1277:1291 two NSCLC types 1277:1291 The glycosylation profiling of fibronectin indicated that the peanut agglutinin (PNA) signal appeared to differentiate two NSCLC types, adenocarcinoma and large cell carcinoma, whereas the protein expression level was similar between these types. 25244057 8 53 theme lectin 1486:1491 arg1 applicable 1496:1505 applicable 1496:1505 applicable 1496:1505 Our glycoproteomics approach together with the concurrent use of an antibody and lectin is applicable to the quantitative and qualitative monitoring of variations in glycosylation of fibronectin specific to certain types of lung cancer tissue. 25244057 8 53 theme lectin 1486:1491 arg1 use 1463:1465 the concurrent use 1448:1465 Our glycoproteomics approach together with the concurrent use of an antibody and lectin 1405:1491 Our glycoproteomics approach together with the concurrent use of an antibody and lectin is applicable to the quantitative and qualitative monitoring of variations in glycosylation of fibronectin specific to certain types of lung cancer tissue. 25244057 8 54 dep antibody 1473:1480 arg1 an 1470:1471 an 1470:1471 an 1470:1471 Our glycoproteomics approach together with the concurrent use of an antibody and lectin is applicable to the quantitative and qualitative monitoring of variations in glycosylation of fibronectin specific to certain types of lung cancer tissue. 25244057 1 55 contain has 189:191 arg1 classification 159:172 Histopathological classification 141:172 Histopathological classification of lung cancer 141:187 Histopathological classification of lung cancer has important implications in the application of clinical practice guidelines and the prediction of patient prognosis. 25244057 1 55 contain has 189:191 arg2 implications 203:214 important implications 193:214 important implications 193:214 Histopathological classification of lung cancer has important implications in the application of clinical practice guidelines and the prediction of patient prognosis. 25244057 7 56 theme glycosylation 1162:1174 arg1 profiling 1176:1184 The glycosylation profiling 1158:1184 The glycosylation profiling of fibronectin 1158:1199 The glycosylation profiling of fibronectin indicated that the peanut agglutinin (PNA) signal appeared to differentiate two NSCLC types, adenocarcinoma and large cell carcinoma, whereas the protein expression level was similar between these types. 25244057 3 57 theme Hippeastrum 551:561 arg1 lectin 570:575 Hippeastrum hybrid lectin 551:575 Hippeastrum hybrid lectin (HHL) 551:581 First, we performed lectin microarray analysis of lung cancer tissue specimens and cell lines and identified Aleuria aurantia lectin (AAL), Hippeastrum hybrid lectin (HHL), and Concanavalia ensiformis agglutinin (ConA) as lectin probes specific to non-small cell lung carcinoma (NSCLC). 25244057 3 57 theme Hippeastrum 551:561 arg1 agglutinin 612:621 Concanavalia ensiformis agglutinin 588:621 Concanavalia ensiformis agglutinin (ConA) 588:628 First, we performed lectin microarray analysis of lung cancer tissue specimens and cell lines and identified Aleuria aurantia lectin (AAL), Hippeastrum hybrid lectin (HHL), and Concanavalia ensiformis agglutinin (ConA) as lectin probes specific to non-small cell lung carcinoma (NSCLC). 25244057 3 57 theme Hippeastrum 551:561 arg1 probes 640:645 lectin probes 633:645 lectin probes specific to non-small cell lung carcinoma (NSCLC) 633:695 First, we performed lectin microarray analysis of lung cancer tissue specimens and cell lines and identified Aleuria aurantia lectin (AAL), Hippeastrum hybrid lectin (HHL), and Concanavalia ensiformis agglutinin (ConA) as lectin probes specific to non-small cell lung carcinoma (NSCLC). 25244057 3 57 theme Hippeastrum 551:561 arg1 lectin 537:542 Aleuria aurantia lectin 520:542 Aleuria aurantia lectin (AAL) 520:548 First, we performed lectin microarray analysis of lung cancer tissue specimens and cell lines and identified Aleuria aurantia lectin (AAL), Hippeastrum hybrid lectin (HHL), and Concanavalia ensiformis agglutinin (ConA) as lectin probes specific to non-small cell lung carcinoma (NSCLC). 25244057 3 57 theme Hippeastrum 551:561 arg1 HHL 578:580 HHL 578:580 HHL 578:580 First, we performed lectin microarray analysis of lung cancer tissue specimens and cell lines and identified Aleuria aurantia lectin (AAL), Hippeastrum hybrid lectin (HHL), and Concanavalia ensiformis agglutinin (ConA) as lectin probes specific to non-small cell lung carcinoma (NSCLC). 25244057 5 58 theme 1092 922:925 arg1 glycoproteins 937:949 1092 AAL-bound glycoproteins 922:949 1092 AAL-bound glycoproteins (316 gene symbols) 922:968 This analysis identified 1092 AAL-bound glycoproteins (316 gene symbols) and 948 HHL/ConA-bound glycoproteins (279 gene symbols). 25244057 5 58 theme 1092 922:925 arg1 symbols 961:967 316 gene symbols 952:967 316 gene symbols 952:967 This analysis identified 1092 AAL-bound glycoproteins (316 gene symbols) and 948 HHL/ConA-bound glycoproteins (279 gene symbols). 25244057 2 59 theme glycobiomarker 340:353 arg1 candidates 355:364 glycobiomarker candidates 340:364 glycobiomarker candidates 340:364 Thus, we focused on discovering glycobiomarker candidates to classify the types of lung cancer tissue. 25244057 5 60 theme gene 956:959 arg1 glycoproteins 937:949 1092 AAL-bound glycoproteins 922:949 1092 AAL-bound glycoproteins (316 gene symbols) 922:968 This analysis identified 1092 AAL-bound glycoproteins (316 gene symbols) and 948 HHL/ConA-bound glycoproteins (279 gene symbols). 25244057 5 60 theme gene 956:959 arg1 symbols 961:967 316 gene symbols 952:967 316 gene symbols 952:967 This analysis identified 1092 AAL-bound glycoproteins (316 gene symbols) and 948 HHL/ConA-bound glycoproteins (279 gene symbols). 25244057 4 61 link N-linked 791:798 arg1 sites 814:818 N-linked glycosylation sites 791:818 N-linked glycosylation sites 791:818 LC-MS-based analysis was performed for the comprehensive identification of glycoproteins and N-linked glycosylation sites using lectin affinity capture of NSCLC-specific glycoforms of glycoproteins. 25244057 1 62 theme practice 247:254 arg1 guidelines 256:265 clinical practice guidelines 238:265 clinical practice guidelines 238:265 Histopathological classification of lung cancer has important implications in the application of clinical practice guidelines and the prediction of patient prognosis. 25244057 8 63 dep together 1434:1441 arg1 with 1443:1446 with 1443:1446 with 1443:1446 Our glycoproteomics approach together with the concurrent use of an antibody and lectin is applicable to the quantitative and qualitative monitoring of variations in glycosylation of fibronectin specific to certain types of lung cancer tissue. 25244057 8 64 from glycosylation 1571:1583 arg1 monitoring 1543:1552 the quantitative and qualitative monitoring 1510:1552 the quantitative and qualitative monitoring of variations in glycosylation of fibronectin specific to certain types of lung cancer tissue 1510:1646 Our glycoproteomics approach together with the concurrent use of an antibody and lectin is applicable to the quantitative and qualitative monitoring of variations in glycosylation of fibronectin specific to certain types of lung cancer tissue. 25244057 3 65 theme Concanavalia 588:599 arg1 agglutinin 612:621 Concanavalia ensiformis agglutinin 588:621 Concanavalia ensiformis agglutinin (ConA) 588:628 First, we performed lectin microarray analysis of lung cancer tissue specimens and cell lines and identified Aleuria aurantia lectin (AAL), Hippeastrum hybrid lectin (HHL), and Concanavalia ensiformis agglutinin (ConA) as lectin probes specific to non-small cell lung carcinoma (NSCLC). 25244057 3 65 theme Concanavalia 588:599 arg1 lectin 570:575 Hippeastrum hybrid lectin 551:575 Hippeastrum hybrid lectin (HHL) 551:581 First, we performed lectin microarray analysis of lung cancer tissue specimens and cell lines and identified Aleuria aurantia lectin (AAL), Hippeastrum hybrid lectin (HHL), and Concanavalia ensiformis agglutinin (ConA) as lectin probes specific to non-small cell lung carcinoma (NSCLC). 25244057 3 65 theme Concanavalia 588:599 arg1 probes 640:645 lectin probes 633:645 lectin probes specific to non-small cell lung carcinoma (NSCLC) 633:695 First, we performed lectin microarray analysis of lung cancer tissue specimens and cell lines and identified Aleuria aurantia lectin (AAL), Hippeastrum hybrid lectin (HHL), and Concanavalia ensiformis agglutinin (ConA) as lectin probes specific to non-small cell lung carcinoma (NSCLC). 25244057 3 65 theme Concanavalia 588:599 arg1 lectin 537:542 Aleuria aurantia lectin 520:542 Aleuria aurantia lectin (AAL) 520:548 First, we performed lectin microarray analysis of lung cancer tissue specimens and cell lines and identified Aleuria aurantia lectin (AAL), Hippeastrum hybrid lectin (HHL), and Concanavalia ensiformis agglutinin (ConA) as lectin probes specific to non-small cell lung carcinoma (NSCLC). 25244057 3 65 theme Concanavalia 588:599 arg1 ConA 624:627 ConA 624:627 ConA 624:627 First, we performed lectin microarray analysis of lung cancer tissue specimens and cell lines and identified Aleuria aurantia lectin (AAL), Hippeastrum hybrid lectin (HHL), and Concanavalia ensiformis agglutinin (ConA) as lectin probes specific to non-small cell lung carcinoma (NSCLC). 25244057 5 66 gly glycoproteins 937:949 arg1 glycoproteins 937:949 1092 AAL-bound glycoproteins 922:949 1092 AAL-bound glycoproteins (316 gene symbols) 922:968 This analysis identified 1092 AAL-bound glycoproteins (316 gene symbols) and 948 HHL/ConA-bound glycoproteins (279 gene symbols). 25244057 5 66 gly glycoproteins 937:949 arg1 symbols 961:967 316 gene symbols 952:967 316 gene symbols 952:967 This analysis identified 1092 AAL-bound glycoproteins (316 gene symbols) and 948 HHL/ConA-bound glycoproteins (279 gene symbols). 25244057 8 67 theme variations 1557:1566 arg1 monitoring 1543:1552 the quantitative and qualitative monitoring 1510:1552 the quantitative and qualitative monitoring of variations in glycosylation of fibronectin specific to certain types of lung cancer tissue 1510:1646 Our glycoproteomics approach together with the concurrent use of an antibody and lectin is applicable to the quantitative and qualitative monitoring of variations in glycosylation of fibronectin specific to certain types of lung cancer tissue. 25244057 6 68 theme cancer 1085:1090 arg1 lines 1097:1101 15 lung cancer cell lines 1077:1101 15 lung cancer cell lines 1077:1101 The lectin microarray-assisted verification using 15 lung cancer cell lines revealed the NSCLC-specific expression of fibronectin. 25244057 8 69 from monitoring 1543:1552 arg1 glycosylation 1571:1583 glycosylation 1571:1583 glycosylation of fibronectin specific to certain types of lung cancer tissue 1571:1646 Our glycoproteomics approach together with the concurrent use of an antibody and lectin is applicable to the quantitative and qualitative monitoring of variations in glycosylation of fibronectin specific to certain types of lung cancer tissue. 25244057 4 70 gly glycoproteins 773:785 arg1 glycoproteins 773:785 glycoproteins 773:785 glycoproteins 773:785 LC-MS-based analysis was performed for the comprehensive identification of glycoproteins and N-linked glycosylation sites using lectin affinity capture of NSCLC-specific glycoforms of glycoproteins. 25244057 1 71 theme lung 177:180 arg1 cancer 182:187 lung cancer 177:187 lung cancer 177:187 Histopathological classification of lung cancer has important implications in the application of clinical practice guidelines and the prediction of patient prognosis. 25244057 8 72 theme fibronectin 1588:1598 arg1 glycosylation 1571:1583 glycosylation 1571:1583 glycosylation of fibronectin specific to certain types of lung cancer tissue 1571:1646 Our glycoproteomics approach together with the concurrent use of an antibody and lectin is applicable to the quantitative and qualitative monitoring of variations in glycosylation of fibronectin specific to certain types of lung cancer tissue. 25244057 7 73 theme NSCLC 1281:1285 arg1 carcinoma 1324:1332 large cell carcinoma 1313:1332 large cell carcinoma 1313:1332 The glycosylation profiling of fibronectin indicated that the peanut agglutinin (PNA) signal appeared to differentiate two NSCLC types, adenocarcinoma and large cell carcinoma, whereas the protein expression level was similar between these types. 25244057 7 73 theme NSCLC 1281:1285 arg1 adenocarcinoma 1294:1307 adenocarcinoma 1294:1307 adenocarcinoma 1294:1307 The glycosylation profiling of fibronectin indicated that the peanut agglutinin (PNA) signal appeared to differentiate two NSCLC types, adenocarcinoma and large cell carcinoma, whereas the protein expression level was similar between these types. 25244057 7 73 theme NSCLC 1281:1285 arg1 types 1287:1291 two NSCLC types 1277:1291 two NSCLC types 1277:1291 The glycosylation profiling of fibronectin indicated that the peanut agglutinin (PNA) signal appeared to differentiate two NSCLC types, adenocarcinoma and large cell carcinoma, whereas the protein expression level was similar between these types. 25244057 5 74 theme 316 952:954 arg1 glycoproteins 937:949 1092 AAL-bound glycoproteins 922:949 1092 AAL-bound glycoproteins (316 gene symbols) 922:968 This analysis identified 1092 AAL-bound glycoproteins (316 gene symbols) and 948 HHL/ConA-bound glycoproteins (279 gene symbols). 25244057 5 74 theme 316 952:954 arg1 symbols 961:967 316 gene symbols 952:967 316 gene symbols 952:967 This analysis identified 1092 AAL-bound glycoproteins (316 gene symbols) and 948 HHL/ConA-bound glycoproteins (279 gene symbols). 25244057 0 75 theme cell 120:123 arg1 carcinoma 130:138 non-small cell lung carcinoma 110:138 non-small cell lung carcinoma 110:138 Glycoproteomics approach for identifying Glycobiomarker candidate molecules for tissue type classification of non-small cell lung carcinoma. 25244057 5 76 theme gene 1012:1015 arg1 symbols 1017:1023 279 gene symbols 1008:1023 279 gene symbols 1008:1023 This analysis identified 1092 AAL-bound glycoproteins (316 gene symbols) and 948 HHL/ConA-bound glycoproteins (279 gene symbols). 25244057 5 76 theme gene 1012:1015 arg1 glycoproteins 993:1005 948 HHL/ConA-bound glycoproteins 974:1005 948 HHL/ConA-bound glycoproteins (279 gene symbols) 974:1024 This analysis identified 1092 AAL-bound glycoproteins (316 gene symbols) and 948 HHL/ConA-bound glycoproteins (279 gene symbols). 25244057 6 77 theme lectin 1031:1036 arg1 verification 1058:1069 The lectin microarray-assisted verification 1027:1069 The lectin microarray-assisted verification using 15 lung cancer cell lines 1027:1101 The lectin microarray-assisted verification using 15 lung cancer cell lines revealed the NSCLC-specific expression of fibronectin. 25244057 8 78 theme glycoproteomics 1409:1423 arg1 approach 1425:1432 Our glycoproteomics approach 1405:1432 Our glycoproteomics approach together with the concurrent use of an antibody and lectin 1405:1491 Our glycoproteomics approach together with the concurrent use of an antibody and lectin is applicable to the quantitative and qualitative monitoring of variations in glycosylation of fibronectin specific to certain types of lung cancer tissue. 25244057 4 79 theme glycoproteins 773:785 arg1 identification 755:768 the comprehensive identification 737:768 the comprehensive identification of glycoproteins and N-linked glycosylation sites 737:818 LC-MS-based analysis was performed for the comprehensive identification of glycoproteins and N-linked glycosylation sites using lectin affinity capture of NSCLC-specific glycoforms of glycoproteins. 25244057 0 80 theme carcinoma 130:138 arg1 classification 92:105 tissue type classification 80:105 tissue type classification of non-small cell lung carcinoma 80:138 Glycoproteomics approach for identifying Glycobiomarker candidate molecules for tissue type classification of non-small cell lung carcinoma. 25244057 1 81 theme clinical 238:245 arg1 guidelines 256:265 clinical practice guidelines 238:265 clinical practice guidelines 238:265 Histopathological classification of lung cancer has important implications in the application of clinical practice guidelines and the prediction of patient prognosis. 25244057 6 82 theme fibronectin 1145:1155 arg1 expression 1131:1140 the NSCLC-specific expression 1112:1140 the NSCLC-specific expression of fibronectin 1112:1155 The lectin microarray-assisted verification using 15 lung cancer cell lines revealed the NSCLC-specific expression of fibronectin. 25244057 8 83 theme lung 1629:1632 arg1 tissue 1641:1646 lung cancer tissue 1629:1646 lung cancer tissue 1629:1646 Our glycoproteomics approach together with the concurrent use of an antibody and lectin is applicable to the quantitative and qualitative monitoring of variations in glycosylation of fibronectin specific to certain types of lung cancer tissue. 25244057 4 84 theme N-linked 791:798 arg1 sites 814:818 N-linked glycosylation sites 791:818 N-linked glycosylation sites 791:818 LC-MS-based analysis was performed for the comprehensive identification of glycoproteins and N-linked glycosylation sites using lectin affinity capture of NSCLC-specific glycoforms of glycoproteins. 25244057 8 85 from variations 1557:1566 arg1 glycosylation 1571:1583 glycosylation 1571:1583 glycosylation of fibronectin specific to certain types of lung cancer tissue 1571:1646 Our glycoproteomics approach together with the concurrent use of an antibody and lectin is applicable to the quantitative and qualitative monitoring of variations in glycosylation of fibronectin specific to certain types of lung cancer tissue. 25244057 5 86 theme HHL/ConA-bound 978:991 arg1 symbols 1017:1023 279 gene symbols 1008:1023 279 gene symbols 1008:1023 This analysis identified 1092 AAL-bound glycoproteins (316 gene symbols) and 948 HHL/ConA-bound glycoproteins (279 gene symbols). 25244057 5 86 theme HHL/ConA-bound 978:991 arg1 glycoproteins 993:1005 948 HHL/ConA-bound glycoproteins 974:1005 948 HHL/ConA-bound glycoproteins (279 gene symbols) 974:1024 This analysis identified 1092 AAL-bound glycoproteins (316 gene symbols) and 948 HHL/ConA-bound glycoproteins (279 gene symbols). 25244057 8 87 theme tissue 1641:1646 arg1 types 1620:1624 certain types 1612:1624 certain types of lung cancer tissue 1612:1646 Our glycoproteomics approach together with the concurrent use of an antibody and lectin is applicable to the quantitative and qualitative monitoring of variations in glycosylation of fibronectin specific to certain types of lung cancer tissue. 25244057 3 88 theme cancer 466:471 arg1 analysis 449:456 lectin microarray analysis 431:456 lectin microarray analysis of lung cancer tissue specimens and cell lines 431:503 First, we performed lectin microarray analysis of lung cancer tissue specimens and cell lines and identified Aleuria aurantia lectin (AAL), Hippeastrum hybrid lectin (HHL), and Concanavalia ensiformis agglutinin (ConA) as lectin probes specific to non-small cell lung carcinoma (NSCLC). 25244057 7 89 theme agglutinin 1227:1236 arg1 signal 1244:1249 the peanut agglutinin (PNA) signal 1216:1249 the peanut agglutinin (PNA) signal 1216:1249 The glycosylation profiling of fibronectin indicated that the peanut agglutinin (PNA) signal appeared to differentiate two NSCLC types, adenocarcinoma and large cell carcinoma, whereas the protein expression level was similar between these types. 25244057 3 90 theme cell 494:497 arg1 lines 499:503 cell lines 494:503 cell lines 494:503 First, we performed lectin microarray analysis of lung cancer tissue specimens and cell lines and identified Aleuria aurantia lectin (AAL), Hippeastrum hybrid lectin (HHL), and Concanavalia ensiformis agglutinin (ConA) as lectin probes specific to non-small cell lung carcinoma (NSCLC). 25244057 7 91 theme protein 1347:1353 arg1 similar 1376:1382 similar 1376:1382 similar 1376:1382 The glycosylation profiling of fibronectin indicated that the peanut agglutinin (PNA) signal appeared to differentiate two NSCLC types, adenocarcinoma and large cell carcinoma, whereas the protein expression level was similar between these types. 25244057 7 91 theme protein 1347:1353 arg1 level 1366:1370 the protein expression level 1343:1370 the protein expression level 1343:1370 The glycosylation profiling of fibronectin indicated that the peanut agglutinin (PNA) signal appeared to differentiate two NSCLC types, adenocarcinoma and large cell carcinoma, whereas the protein expression level was similar between these types. 25244057 3 92 theme microarray 438:447 arg1 analysis 449:456 lectin microarray analysis 431:456 lectin microarray analysis of lung cancer tissue specimens and cell lines 431:503 First, we performed lectin microarray analysis of lung cancer tissue specimens and cell lines and identified Aleuria aurantia lectin (AAL), Hippeastrum hybrid lectin (HHL), and Concanavalia ensiformis agglutinin (ConA) as lectin probes specific to non-small cell lung carcinoma (NSCLC). 25244057 4 93 theme NSCLC-specific 853:866 arg1 glycoforms 868:877 NSCLC-specific glycoforms 853:877 NSCLC-specific glycoforms of glycoproteins 853:894 LC-MS-based analysis was performed for the comprehensive identification of glycoproteins and N-linked glycosylation sites using lectin affinity capture of NSCLC-specific glycoforms of glycoproteins. 25244057 3 94 theme cell 669:672 arg1 NSCLC 690:694 NSCLC 690:694 NSCLC 690:694 First, we performed lectin microarray analysis of lung cancer tissue specimens and cell lines and identified Aleuria aurantia lectin (AAL), Hippeastrum hybrid lectin (HHL), and Concanavalia ensiformis agglutinin (ConA) as lectin probes specific to non-small cell lung carcinoma (NSCLC). 25244057 3 94 theme cell 669:672 arg1 carcinoma 679:687 non-small cell lung carcinoma 659:687 non-small cell lung carcinoma (NSCLC) 659:695 First, we performed lectin microarray analysis of lung cancer tissue specimens and cell lines and identified Aleuria aurantia lectin (AAL), Hippeastrum hybrid lectin (HHL), and Concanavalia ensiformis agglutinin (ConA) as lectin probes specific to non-small cell lung carcinoma (NSCLC). 25244057 4 95 theme sites 814:818 arg1 identification 755:768 the comprehensive identification 737:768 the comprehensive identification of glycoproteins and N-linked glycosylation sites 737:818 LC-MS-based analysis was performed for the comprehensive identification of glycoproteins and N-linked glycosylation sites using lectin affinity capture of NSCLC-specific glycoforms of glycoproteins. 25244057 8 96 gly glycosylation 1571:1583 arg1 fibronectin 1588:1598 fibronectin 1588:1598 fibronectin specific to certain types of lung cancer tissue 1588:1646 Our glycoproteomics approach together with the concurrent use of an antibody and lectin is applicable to the quantitative and qualitative monitoring of variations in glycosylation of fibronectin specific to certain types of lung cancer tissue. 25244057 4 97 theme lectin 826:831 arg1 capture 842:848 lectin affinity capture 826:848 lectin affinity capture of NSCLC-specific glycoforms of glycoproteins 826:894 LC-MS-based analysis was performed for the comprehensive identification of glycoproteins and N-linked glycosylation sites using lectin affinity capture of NSCLC-specific glycoforms of glycoproteins. 25244057 2 98 theme tissue 403:408 arg1 types 382:386 the types 378:386 the types of lung cancer tissue 378:408 Thus, we focused on discovering glycobiomarker candidates to classify the types of lung cancer tissue. 25212012 8 0 theme FSH 1244:1246 arg1 Folltropin-V 1261:1272 Folltropin-V 1261:1272 Folltropin-V 1261:1272 Single injection of this recombinant FSH could induce folliculogenesis and ovulation in rats, the efficacy was similar with the commercially available FSH preparation (Folltropin-V) administrated 8 times consecutively. 25212012 8 0 theme FSH 1244:1246 arg1 preparation 1248:1258 the commercially available FSH preparation 1217:1258 the commercially available FSH preparation (Folltropin-V) administrated 8 times consecutively 1217:1309 Single injection of this recombinant FSH could induce folliculogenesis and ovulation in rats, the efficacy was similar with the commercially available FSH preparation (Folltropin-V) administrated 8 times consecutively. 25212012 7 1 theme CHO-K1 1040:1045 arg1 strain 1052:1057 CHO-K1 cell strain 1040:1057 CHO-K1 cell strain 1040:1057 The recombinant FSH expression level in CHO-K1 cell strain in serum-free culture was 3 mg/L. 25212012 1 2 theme pituitary 119:127 arg1 hormone 142:148 a pituitary glycoprotein hormone 117:148 a pituitary glycoprotein hormone that is essential for the development of ovarian follicles and testicular seminiferous tubules 117:243 Follicle-stimulating hormone (FSH) is a pituitary glycoprotein hormone that is essential for the development of ovarian follicles and testicular seminiferous tubules. 25212012 1 2 theme pituitary 119:127 arg1 essential 158:166 essential 158:166 essential 158:166 Follicle-stimulating hormone (FSH) is a pituitary glycoprotein hormone that is essential for the development of ovarian follicles and testicular seminiferous tubules. 25212012 1 2 theme pituitary 119:127 arg1 hormone 100:106 Follicle-stimulating hormone 79:106 Follicle-stimulating hormone (FSH) 79:112 Follicle-stimulating hormone (FSH) is a pituitary glycoprotein hormone that is essential for the development of ovarian follicles and testicular seminiferous tubules. 25212012 1 3 theme seminiferous 224:235 arg1 tubules 237:243 testicular seminiferous tubules 213:243 testicular seminiferous tubules 213:243 Follicle-stimulating hormone (FSH) is a pituitary glycoprotein hormone that is essential for the development of ovarian follicles and testicular seminiferous tubules. 25212012 7 4 theme cell 1047:1050 arg1 strain 1052:1057 CHO-K1 cell strain 1040:1057 CHO-K1 cell strain 1040:1057 The recombinant FSH expression level in CHO-K1 cell strain in serum-free culture was 3 mg/L. 25212012 5 5 theme positive 827:834 arg1 transformants 836:848 positive transformants 827:848 positive transformants 827:848 The pcDNA3.1-FSH was linearized and transfected into CHO-K1, positive transformants were selected by G418 and confirmed by PCR and Western blotting. 25212012 1 6 theme glycoprotein 129:140 arg1 hormone 142:148 a pituitary glycoprotein hormone 117:148 a pituitary glycoprotein hormone that is essential for the development of ovarian follicles and testicular seminiferous tubules 117:243 Follicle-stimulating hormone (FSH) is a pituitary glycoprotein hormone that is essential for the development of ovarian follicles and testicular seminiferous tubules. 25212012 1 6 theme glycoprotein 129:140 arg1 essential 158:166 essential 158:166 essential 158:166 Follicle-stimulating hormone (FSH) is a pituitary glycoprotein hormone that is essential for the development of ovarian follicles and testicular seminiferous tubules. 25212012 1 6 theme glycoprotein 129:140 arg1 hormone 100:106 Follicle-stimulating hormone 79:106 Follicle-stimulating hormone (FSH) 79:112 Follicle-stimulating hormone (FSH) is a pituitary glycoprotein hormone that is essential for the development of ovarian follicles and testicular seminiferous tubules. 25212012 1 7 theme tubules 237:243 arg1 development 176:186 the development 172:186 the development of ovarian follicles and testicular seminiferous tubules 172:243 Follicle-stimulating hormone (FSH) is a pituitary glycoprotein hormone that is essential for the development of ovarian follicles and testicular seminiferous tubules. 25212012 0 8 from [Expression 0:10 arg1 cell 44:47 CHO cell 40:47 CHO cell 40:47 [Expression of human long-acting FSH in CHO cell and its bioactivity in vivo]. 25212012 1 9 theme Follicle-stimulating 79:98 arg1 FSH 109:111 FSH 109:111 FSH 109:111 Follicle-stimulating hormone (FSH) is a pituitary glycoprotein hormone that is essential for the development of ovarian follicles and testicular seminiferous tubules. 25212012 1 9 theme Follicle-stimulating 79:98 arg1 hormone 100:106 Follicle-stimulating hormone 79:106 Follicle-stimulating hormone (FSH) 79:112 Follicle-stimulating hormone (FSH) is a pituitary glycoprotein hormone that is essential for the development of ovarian follicles and testicular seminiferous tubules. 25212012 1 9 theme Follicle-stimulating 79:98 arg1 essential 158:166 essential 158:166 essential 158:166 Follicle-stimulating hormone (FSH) is a pituitary glycoprotein hormone that is essential for the development of ovarian follicles and testicular seminiferous tubules. 25212012 1 9 theme Follicle-stimulating 79:98 arg1 hormone 142:148 a pituitary glycoprotein hormone 117:148 a pituitary glycoprotein hormone that is essential for the development of ovarian follicles and testicular seminiferous tubules 117:243 Follicle-stimulating hormone (FSH) is a pituitary glycoprotein hormone that is essential for the development of ovarian follicles and testicular seminiferous tubules. 25212012 6 10 theme single 917:922 arg1 FSH 942:944 A single chain recombinant FSH 915:944 A single chain recombinant FSH 915:944 A single chain recombinant FSH was expressed, with molecular weight of about 49 kDa. 25212012 0 11 from cell 44:47 arg1 bioactivity 57:67 its bioactivity 53:67 its bioactivity in vivo 53:75 [Expression of human long-acting FSH in CHO cell and its bioactivity in vivo]. 25212012 0 11 from cell 44:47 arg1 [Expression 0:10 [Expression 0:10 [Expression of human long-acting FSH in CHO cell 0:47 [Expression of human long-acting FSH in CHO cell and its bioactivity in vivo]. 25212012 5 12 theme Western 897:903 arg1 blotting 905:912 Western blotting 897:912 Western blotting 897:912 The pcDNA3.1-FSH was linearized and transfected into CHO-K1, positive transformants were selected by G418 and confirmed by PCR and Western blotting. 25212012 3 13 theme present 442:448 arg1 study 450:454 the present study 438:454 the present study 438:454 The goal of the present study was to increase FSH glycosylation, in order to develop a long-acting recombinant FSH. 25212012 4 14 theme glycosylation 640:652 arg1 sites 654:658 two N-linked glycosylation sites 627:658 two N-linked glycosylation sites 627:658 The cDNA of native alpha and beta subunit of human FSH was linked by a sequence with two N-linked glycosylation sites, and the resulted DNA was inserted into pcDNA3.1 vector to generate a recombinant vector of pcDNA3.1-FSH. 25212012 7 15 theme FSH 1016:1018 arg1 mg/L 1087:1090 3 mg/L 1085:1090 3 mg/L 1085:1090 The recombinant FSH expression level in CHO-K1 cell strain in serum-free culture was 3 mg/L. 25212012 7 15 theme FSH 1016:1018 arg1 level 1031:1035 The recombinant FSH expression level 1000:1035 The recombinant FSH expression level in CHO-K1 cell strain in serum-free culture 1000:1079 The recombinant FSH expression level in CHO-K1 cell strain in serum-free culture was 3 mg/L. 25212012 2 16 theme short 261:265 arg1 half-life 267:275 The relatively short half-life 246:275 The relatively short half-life of FSH in vivo 246:290 The relatively short half-life of FSH in vivo requires daily injections for more than 10 days that is inconvenient and possibly contribute to the stress perceived by the patients. 25212012 4 17 with sequence 613:620 arg1 sites 654:658 two N-linked glycosylation sites 627:658 two N-linked glycosylation sites 627:658 The cDNA of native alpha and beta subunit of human FSH was linked by a sequence with two N-linked glycosylation sites, and the resulted DNA was inserted into pcDNA3.1 vector to generate a recombinant vector of pcDNA3.1-FSH. 25212012 6 18 theme recombinant 930:940 arg1 FSH 942:944 A single chain recombinant FSH 915:944 A single chain recombinant FSH 915:944 A single chain recombinant FSH was expressed, with molecular weight of about 49 kDa. 25212012 4 19 link N-linked 631:638 arg1 sites 654:658 two N-linked glycosylation sites 627:658 two N-linked glycosylation sites 627:658 The cDNA of native alpha and beta subunit of human FSH was linked by a sequence with two N-linked glycosylation sites, and the resulted DNA was inserted into pcDNA3.1 vector to generate a recombinant vector of pcDNA3.1-FSH. 25212012 4 20 theme FSH 593:595 arg1 alpha 561:565 native alpha and beta subunit 554:582 alpha 561:565 The cDNA of native alpha and beta subunit of human FSH was linked by a sequence with two N-linked glycosylation sites, and the resulted DNA was inserted into pcDNA3.1 vector to generate a recombinant vector of pcDNA3.1-FSH. 25212012 4 20 theme FSH 593:595 arg1 subunit 576:582 native alpha and beta subunit 554:582 subunit 576:582 The cDNA of native alpha and beta subunit of human FSH was linked by a sequence with two N-linked glycosylation sites, and the resulted DNA was inserted into pcDNA3.1 vector to generate a recombinant vector of pcDNA3.1-FSH. 25212012 0 21 from FSH 33:35 arg1 cell 44:47 CHO cell 40:47 CHO cell 40:47 [Expression of human long-acting FSH in CHO cell and its bioactivity in vivo]. 25212012 3 22 theme long-acting 513:523 arg1 FSH 537:539 a long-acting recombinant FSH 511:539 a long-acting recombinant FSH 511:539 The goal of the present study was to increase FSH glycosylation, in order to develop a long-acting recombinant FSH. 25212012 8 23 theme Single 1093:1098 arg1 injection 1100:1108 Single injection 1093:1108 Single injection of this recombinant FSH 1093:1132 Single injection of this recombinant FSH could induce folliculogenesis and ovulation in rats, the efficacy was similar with the commercially available FSH preparation (Folltropin-V) administrated 8 times consecutively. 25212012 7 24 theme recombinant 1004:1014 arg1 mg/L 1087:1090 3 mg/L 1085:1090 3 mg/L 1085:1090 The recombinant FSH expression level in CHO-K1 cell strain in serum-free culture was 3 mg/L. 25212012 7 24 theme recombinant 1004:1014 arg1 level 1031:1035 The recombinant FSH expression level 1000:1035 The recombinant FSH expression level in CHO-K1 cell strain in serum-free culture 1000:1079 The recombinant FSH expression level in CHO-K1 cell strain in serum-free culture was 3 mg/L. 25212012 3 25 theme recombinant 525:535 arg1 FSH 537:539 a long-acting recombinant FSH 511:539 a long-acting recombinant FSH 511:539 The goal of the present study was to increase FSH glycosylation, in order to develop a long-acting recombinant FSH. 25212012 0 26 theme long-acting 21:31 arg1 FSH 33:35 human long-acting FSH 15:35 human long-acting FSH in CHO cell 15:47 [Expression of human long-acting FSH in CHO cell and its bioactivity in vivo]. 25212012 6 27 theme molecular 966:974 arg1 weight 976:981 molecular weight 966:981 molecular weight of about 49 kDa 966:997 A single chain recombinant FSH was expressed, with molecular weight of about 49 kDa. 25212012 4 28 theme subunit 576:582 arg1 cDNA 546:549 The cDNA 542:549 The cDNA of native alpha and beta subunit of human FSH 542:595 The cDNA of native alpha and beta subunit of human FSH was linked by a sequence with two N-linked glycosylation sites, and the resulted DNA was inserted into pcDNA3.1 vector to generate a recombinant vector of pcDNA3.1-FSH. 25212012 0 29 theme human 15:19 arg1 FSH 33:35 human long-acting FSH 15:35 human long-acting FSH in CHO cell 15:47 [Expression of human long-acting FSH in CHO cell and its bioactivity in vivo]. 25212012 4 30 gly glycosylation 640:652 arg2 sites 654:658 two N-linked glycosylation sites 627:658 two N-linked glycosylation sites 627:658 The cDNA of native alpha and beta subunit of human FSH was linked by a sequence with two N-linked glycosylation sites, and the resulted DNA was inserted into pcDNA3.1 vector to generate a recombinant vector of pcDNA3.1-FSH. 25212012 4 30 gly glycosylation 640:652 arg2 two 627:629 two 627:629 two 627:629 The cDNA of native alpha and beta subunit of human FSH was linked by a sequence with two N-linked glycosylation sites, and the resulted DNA was inserted into pcDNA3.1 vector to generate a recombinant vector of pcDNA3.1-FSH. 25212012 9 31 dep suggested 1324:1332 arg1 produced 1356:1363 produced 1356:1363 suggested a long-acting FSH was produced successfully 1324:1376 The results suggested a long-acting FSH was produced successfully. 25212012 2 32 theme FSH 280:282 arg1 half-life 267:275 The relatively short half-life 246:275 The relatively short half-life of FSH in vivo 246:290 The relatively short half-life of FSH in vivo requires daily injections for more than 10 days that is inconvenient and possibly contribute to the stress perceived by the patients. 25212012 4 33 theme beta 571:574 arg1 subunit 576:582 native alpha and beta subunit 554:582 subunit 576:582 The cDNA of native alpha and beta subunit of human FSH was linked by a sequence with two N-linked glycosylation sites, and the resulted DNA was inserted into pcDNA3.1 vector to generate a recombinant vector of pcDNA3.1-FSH. 25212012 7 34 theme serum-free 1062:1071 arg1 culture 1073:1079 serum-free culture 1062:1079 serum-free culture 1062:1079 The recombinant FSH expression level in CHO-K1 cell strain in serum-free culture was 3 mg/L. 25212012 0 35 from bioactivity 57:67 arg1 cell 44:47 CHO cell 40:47 CHO cell 40:47 [Expression of human long-acting FSH in CHO cell and its bioactivity in vivo]. 25212012 4 36 theme human 587:591 arg1 FSH 593:595 human FSH 587:595 human FSH 587:595 The cDNA of native alpha and beta subunit of human FSH was linked by a sequence with two N-linked glycosylation sites, and the resulted DNA was inserted into pcDNA3.1 vector to generate a recombinant vector of pcDNA3.1-FSH. 25212012 0 37 theme FSH 33:35 arg1 bioactivity 57:67 its bioactivity 53:67 its bioactivity in vivo 53:75 [Expression of human long-acting FSH in CHO cell and its bioactivity in vivo]. 25212012 0 37 theme FSH 33:35 arg1 [Expression 0:10 [Expression 0:10 [Expression of human long-acting FSH in CHO cell 0:47 [Expression of human long-acting FSH in CHO cell and its bioactivity in vivo]. 25212012 7 38 from level 1031:1035 arg1 strain 1052:1057 CHO-K1 cell strain 1040:1057 CHO-K1 cell strain 1040:1057 The recombinant FSH expression level in CHO-K1 cell strain in serum-free culture was 3 mg/L. 25212012 7 38 from level 1031:1035 arg1 culture 1073:1079 serum-free culture 1062:1079 serum-free culture 1062:1079 The recombinant FSH expression level in CHO-K1 cell strain in serum-free culture was 3 mg/L. 25212012 6 39 theme chain 924:928 arg1 FSH 942:944 A single chain recombinant FSH 915:944 A single chain recombinant FSH 915:944 A single chain recombinant FSH was expressed, with molecular weight of about 49 kDa. 25212012 4 40 attach linked 601:606 arg3 sequence 613:620 a sequence 611:620 a sequence with two N-linked glycosylation sites 611:658 The cDNA of native alpha and beta subunit of human FSH was linked by a sequence with two N-linked glycosylation sites, and the resulted DNA was inserted into pcDNA3.1 vector to generate a recombinant vector of pcDNA3.1-FSH. 25212012 4 40 attach linked 601:606 arg2 cDNA 546:549 The cDNA 542:549 The cDNA of native alpha and beta subunit of human FSH 542:595 The cDNA of native alpha and beta subunit of human FSH was linked by a sequence with two N-linked glycosylation sites, and the resulted DNA was inserted into pcDNA3.1 vector to generate a recombinant vector of pcDNA3.1-FSH. 25212012 4 41 theme recombinant 730:740 arg1 vector 742:747 a recombinant vector 728:747 a recombinant vector of pcDNA3.1-FSH 728:763 The cDNA of native alpha and beta subunit of human FSH was linked by a sequence with two N-linked glycosylation sites, and the resulted DNA was inserted into pcDNA3.1 vector to generate a recombinant vector of pcDNA3.1-FSH. 25212012 9 42 theme long-acting 1336:1346 arg1 FSH 1348:1350 a long-acting FSH 1334:1350 a long-acting FSH 1334:1350 The results suggested a long-acting FSH was produced successfully. 25212012 8 43 theme FSH 1130:1132 arg1 injection 1100:1108 Single injection 1093:1108 Single injection of this recombinant FSH 1093:1132 Single injection of this recombinant FSH could induce folliculogenesis and ovulation in rats, the efficacy was similar with the commercially available FSH preparation (Folltropin-V) administrated 8 times consecutively. 25212012 4 44 theme pcDNA3.1-FSH 752:763 arg1 vector 742:747 a recombinant vector 728:747 a recombinant vector of pcDNA3.1-FSH 728:763 The cDNA of native alpha and beta subunit of human FSH was linked by a sequence with two N-linked glycosylation sites, and the resulted DNA was inserted into pcDNA3.1 vector to generate a recombinant vector of pcDNA3.1-FSH. 25212012 8 45 from ovulation 1168:1176 arg1 rats 1181:1184 rats 1181:1184 rats 1181:1184 Single injection of this recombinant FSH could induce folliculogenesis and ovulation in rats, the efficacy was similar with the commercially available FSH preparation (Folltropin-V) administrated 8 times consecutively. 25212012 3 46 theme study 450:454 arg1 goal 430:433 The goal 426:433 The goal of the present study 426:454 The goal of the present study was to increase FSH glycosylation, in order to develop a long-acting recombinant FSH. 25212012 0 47 theme CHO 40:42 arg1 cell 44:47 CHO cell 40:47 CHO cell 40:47 [Expression of human long-acting FSH in CHO cell and its bioactivity in vivo]. 25212012 7 48 theme expression 1020:1029 arg1 mg/L 1087:1090 3 mg/L 1085:1090 3 mg/L 1085:1090 The recombinant FSH expression level in CHO-K1 cell strain in serum-free culture was 3 mg/L. 25212012 7 48 theme expression 1020:1029 arg1 level 1031:1035 The recombinant FSH expression level 1000:1035 The recombinant FSH expression level in CHO-K1 cell strain in serum-free culture 1000:1079 The recombinant FSH expression level in CHO-K1 cell strain in serum-free culture was 3 mg/L. 25212012 8 49 theme recombinant 1118:1128 arg1 FSH 1130:1132 this recombinant FSH 1113:1132 this recombinant FSH 1113:1132 Single injection of this recombinant FSH could induce folliculogenesis and ovulation in rats, the efficacy was similar with the commercially available FSH preparation (Folltropin-V) administrated 8 times consecutively. 25212012 4 50 theme N-linked 631:638 arg1 sites 654:658 two N-linked glycosylation sites 627:658 two N-linked glycosylation sites 627:658 The cDNA of native alpha and beta subunit of human FSH was linked by a sequence with two N-linked glycosylation sites, and the resulted DNA was inserted into pcDNA3.1 vector to generate a recombinant vector of pcDNA3.1-FSH. 25212012 1 51 gly glycoprotein 129:140 arg1 glycoprotein 129:140 a pituitary glycoprotein hormone 117:148 a pituitary glycoprotein hormone that is essential for the development of ovarian follicles and testicular seminiferous tubules 117:243 Follicle-stimulating hormone (FSH) is a pituitary glycoprotein hormone that is essential for the development of ovarian follicles and testicular seminiferous tubules. 25212012 8 52 from folliculogenesis 1147:1162 arg1 rats 1181:1184 rats 1181:1184 rats 1181:1184 Single injection of this recombinant FSH could induce folliculogenesis and ovulation in rats, the efficacy was similar with the commercially available FSH preparation (Folltropin-V) administrated 8 times consecutively. 25212012 1 53 theme ovarian 191:197 arg1 follicles 199:207 ovarian follicles 191:207 ovarian follicles 191:207 Follicle-stimulating hormone (FSH) is a pituitary glycoprotein hormone that is essential for the development of ovarian follicles and testicular seminiferous tubules. 25212012 8 54 theme available 1234:1242 arg1 Folltropin-V 1261:1272 Folltropin-V 1261:1272 Folltropin-V 1261:1272 Single injection of this recombinant FSH could induce folliculogenesis and ovulation in rats, the efficacy was similar with the commercially available FSH preparation (Folltropin-V) administrated 8 times consecutively. 25212012 8 54 theme available 1234:1242 arg1 preparation 1248:1258 the commercially available FSH preparation 1217:1258 the commercially available FSH preparation (Folltropin-V) administrated 8 times consecutively 1217:1309 Single injection of this recombinant FSH could induce folliculogenesis and ovulation in rats, the efficacy was similar with the commercially available FSH preparation (Folltropin-V) administrated 8 times consecutively. 25212012 4 55 theme resulted 669:676 arg1 DNA 678:680 the resulted DNA 665:680 the resulted DNA 665:680 The cDNA of native alpha and beta subunit of human FSH was linked by a sequence with two N-linked glycosylation sites, and the resulted DNA was inserted into pcDNA3.1 vector to generate a recombinant vector of pcDNA3.1-FSH. 25212012 2 56 theme daily 301:305 arg1 injections 307:316 daily injections 301:316 daily injections for more than 10 days that is inconvenient and possibly contribute to the stress perceived by the patients 301:423 The relatively short half-life of FSH in vivo requires daily injections for more than 10 days that is inconvenient and possibly contribute to the stress perceived by the patients. 25212012 1 57 theme follicles 199:207 arg1 development 176:186 the development 172:186 the development of ovarian follicles and testicular seminiferous tubules 172:243 Follicle-stimulating hormone (FSH) is a pituitary glycoprotein hormone that is essential for the development of ovarian follicles and testicular seminiferous tubules. 25212012 8 58 with similar 1204:1210 arg1 Folltropin-V 1261:1272 Folltropin-V 1261:1272 Folltropin-V 1261:1272 Single injection of this recombinant FSH could induce folliculogenesis and ovulation in rats, the efficacy was similar with the commercially available FSH preparation (Folltropin-V) administrated 8 times consecutively. 25212012 8 58 with similar 1204:1210 arg1 preparation 1248:1258 the commercially available FSH preparation 1217:1258 the commercially available FSH preparation (Folltropin-V) administrated 8 times consecutively 1217:1309 Single injection of this recombinant FSH could induce folliculogenesis and ovulation in rats, the efficacy was similar with the commercially available FSH preparation (Folltropin-V) administrated 8 times consecutively. 25212012 3 59 theme FSH 472:474 arg1 glycosylation 476:488 FSH glycosylation 472:488 FSH glycosylation 472:488 The goal of the present study was to increase FSH glycosylation, in order to develop a long-acting recombinant FSH. 25212012 6 60 theme kDa 995:997 arg1 weight 976:981 molecular weight 966:981 molecular weight of about 49 kDa 966:997 A single chain recombinant FSH was expressed, with molecular weight of about 49 kDa. 25212012 4 61 theme alpha 561:565 arg1 cDNA 546:549 The cDNA 542:549 The cDNA of native alpha and beta subunit of human FSH 542:595 The cDNA of native alpha and beta subunit of human FSH was linked by a sequence with two N-linked glycosylation sites, and the resulted DNA was inserted into pcDNA3.1 vector to generate a recombinant vector of pcDNA3.1-FSH. 25212012 4 62 theme native 554:559 arg1 alpha 561:565 native alpha and beta subunit 554:582 alpha 561:565 The cDNA of native alpha and beta subunit of human FSH was linked by a sequence with two N-linked glycosylation sites, and the resulted DNA was inserted into pcDNA3.1 vector to generate a recombinant vector of pcDNA3.1-FSH. 25212012 1 63 theme testicular 213:222 arg1 tubules 237:243 testicular seminiferous tubules 213:243 testicular seminiferous tubules 213:243 Follicle-stimulating hormone (FSH) is a pituitary glycoprotein hormone that is essential for the development of ovarian follicles and testicular seminiferous tubules. 26858738 6 0 theme IgA1 1138:1141 arg1 region 1161:1166 the IgA1 alpha chain hinge region 1134:1166 the IgA1 alpha chain hinge region 1134:1166 Analysis of the peptide carrying nine potential O-glycosylation sites in the IgA1 alpha chain hinge region showed the presence of plant-specific modifications including hydroxyproline formation and the attachment of pentoses. 26858738 3 1 theme immunoglobulin 511:524 arg1 IgA 529:531 IgA 529:531 IgA 529:531 Compared to immunoglobulin G (IgG), less effort has been undertaken to express immunoglobulin A (IgA), which is the most prevalent antibody class at mucosal sites and a promising candidate for novel recombinant biopharmaceuticals with enhanced anti-tumor activity. 26858738 3 1 theme immunoglobulin 511:524 arg1 A 526:526 immunoglobulin A 511:526 immunoglobulin A (IgA) 511:532 Compared to immunoglobulin G (IgG), less effort has been undertaken to express immunoglobulin A (IgA), which is the most prevalent antibody class at mucosal sites and a promising candidate for novel recombinant biopharmaceuticals with enhanced anti-tumor activity. 26858738 3 1 theme immunoglobulin 511:524 arg1 class 572:576 the most prevalent antibody class 544:576 the most prevalent antibody class at mucosal sites 544:593 Compared to immunoglobulin G (IgG), less effort has been undertaken to express immunoglobulin A (IgA), which is the most prevalent antibody class at mucosal sites and a promising candidate for novel recombinant biopharmaceuticals with enhanced anti-tumor activity. 26858738 2 2 theme plant-based 272:282 arg1 systems 295:301 plant-based expression systems 272:301 plant-based expression systems 272:301 The recent development of plant-based expression systems has demonstrated that plants are well-suited for the production of recombinant monoclonal antibodies with defined glycosylation. 26858738 3 3 with biopharmaceuticals 643:660 arg1 activity 687:694 enhanced anti-tumor activity 667:694 enhanced anti-tumor activity 667:694 Compared to immunoglobulin G (IgG), less effort has been undertaken to express immunoglobulin A (IgA), which is the most prevalent antibody class at mucosal sites and a promising candidate for novel recombinant biopharmaceuticals with enhanced anti-tumor activity. 26858738 6 4 theme hydroxyproline 1230:1243 arg1 formation 1245:1253 hydroxyproline formation 1230:1253 hydroxyproline formation 1230:1253 Analysis of the peptide carrying nine potential O-glycosylation sites in the IgA1 alpha chain hinge region showed the presence of plant-specific modifications including hydroxyproline formation and the attachment of pentoses. 26858738 3 5 theme immunoglobulin 444:457 arg1 IgG 462:464 IgG 462:464 IgG 462:464 Compared to immunoglobulin G (IgG), less effort has been undertaken to express immunoglobulin A (IgA), which is the most prevalent antibody class at mucosal sites and a promising candidate for novel recombinant biopharmaceuticals with enhanced anti-tumor activity. 26858738 3 5 theme immunoglobulin 444:457 arg1 G 459:459 immunoglobulin G 444:459 immunoglobulin G (IgG) 444:465 Compared to immunoglobulin G (IgG), less effort has been undertaken to express immunoglobulin A (IgA), which is the most prevalent antibody class at mucosal sites and a promising candidate for novel recombinant biopharmaceuticals with enhanced anti-tumor activity. 26858738 6 6 theme modifications 1206:1218 arg1 presence 1179:1186 the presence 1175:1186 the presence of plant-specific modifications including hydroxyproline formation and the attachment of pentoses 1175:1284 Analysis of the peptide carrying nine potential O-glycosylation sites in the IgA1 alpha chain hinge region showed the presence of plant-specific modifications including hydroxyproline formation and the attachment of pentoses. 26858738 3 7 theme prevalent 553:561 arg1 A 526:526 immunoglobulin A 511:526 immunoglobulin A (IgA) 511:532 Compared to immunoglobulin G (IgG), less effort has been undertaken to express immunoglobulin A (IgA), which is the most prevalent antibody class at mucosal sites and a promising candidate for novel recombinant biopharmaceuticals with enhanced anti-tumor activity. 26858738 3 7 theme prevalent 553:561 arg1 class 572:576 the most prevalent antibody class 544:576 the most prevalent antibody class at mucosal sites 544:593 Compared to immunoglobulin G (IgG), less effort has been undertaken to express immunoglobulin A (IgA), which is the most prevalent antibody class at mucosal sites and a promising candidate for novel recombinant biopharmaceuticals with enhanced anti-tumor activity. 26858738 2 8 theme systems 295:301 arg1 development 257:267 The recent development 246:267 The recent development of plant-based expression systems 246:301 The recent development of plant-based expression systems has demonstrated that plants are well-suited for the production of recombinant monoclonal antibodies with defined glycosylation. 26858738 1 9 theme therapeutic 115:125 arg1 antibodies 127:136 therapeutic antibodies 115:136 therapeutic antibodies 115:136 The production of therapeutic antibodies to combat pathogens and treat diseases, such as cancer is of great interest for the biotechnology industry. 26858738 3 10 theme mucosal 581:587 arg1 sites 589:593 mucosal sites 581:593 mucosal sites 581:593 Compared to immunoglobulin G (IgG), less effort has been undertaken to express immunoglobulin A (IgA), which is the most prevalent antibody class at mucosal sites and a promising candidate for novel recombinant biopharmaceuticals with enhanced anti-tumor activity. 26858738 1 11 theme great 199:203 arg1 interest 205:212 great interest 199:212 great interest for the biotechnology industry 199:243 The production of therapeutic antibodies to combat pathogens and treat diseases, such as cancer is of great interest for the biotechnology industry. 26858738 7 12 theme plant-produced 1451:1464 arg1 IgA1 1466:1469 plant-produced IgA1 1451:1469 plant-produced IgA1 1451:1469 By co-expression of enzymes required for initiation and elongation of human O-glycosylation it was possible to generate disialylated mucin-type core 1 O-glycans on plant-produced IgA1. 26858738 5 13 theme terminal 953:960 arg1 N-acetylglucosamine 962:980 terminal N-acetylglucosamine 953:980 terminal N-acetylglucosamine present on the N-glycosylation site of the CH2 domain in the IgA1 alpha chain 953:1058 Mass spectrometric analysis of IgA1 glycopeptides revealed the presence of complex biantennary N-glycans with terminal N-acetylglucosamine present on the N-glycosylation site of the CH2 domain in the IgA1 alpha chain. 26858738 6 14 theme pentoses 1277:1284 arg1 formation 1245:1253 hydroxyproline formation 1230:1253 hydroxyproline formation 1230:1253 Analysis of the peptide carrying nine potential O-glycosylation sites in the IgA1 alpha chain hinge region showed the presence of plant-specific modifications including hydroxyproline formation and the attachment of pentoses. 26858738 6 14 theme pentoses 1277:1284 arg1 attachment 1263:1272 the attachment 1259:1272 the attachment of pentoses 1259:1284 Analysis of the peptide carrying nine potential O-glycosylation sites in the IgA1 alpha chain hinge region showed the presence of plant-specific modifications including hydroxyproline formation and the attachment of pentoses. 26858738 4 15 theme recombinant 728:738 arg1 IgA1 746:749 recombinant human IgA1 728:749 recombinant human IgA1 against the VP8* rotavirus antigen 728:784 Here, we transiently expressed recombinant human IgA1 against the VP8* rotavirus antigen in glyco-engineered ΔXT/FT Nicotiana benthamiana plants. 26858738 3 16 theme promising 601:609 arg1 candidate 611:619 a promising candidate 599:619 a promising candidate for novel recombinant biopharmaceuticals with enhanced anti-tumor activity 599:694 Compared to immunoglobulin G (IgG), less effort has been undertaken to express immunoglobulin A (IgA), which is the most prevalent antibody class at mucosal sites and a promising candidate for novel recombinant biopharmaceuticals with enhanced anti-tumor activity. 26858738 5 17 theme present 982:988 arg1 N-acetylglucosamine 962:980 terminal N-acetylglucosamine 953:980 terminal N-acetylglucosamine present on the N-glycosylation site of the CH2 domain in the IgA1 alpha chain 953:1058 Mass spectrometric analysis of IgA1 glycopeptides revealed the presence of complex biantennary N-glycans with terminal N-acetylglucosamine present on the N-glycosylation site of the CH2 domain in the IgA1 alpha chain. 26858738 8 18 theme recombinant 1570:1580 arg1 IgA1 1582:1585 recombinant IgA1 1570:1585 recombinant IgA1 with defined human-type N- and O-linked glycans 1570:1633 Our data demonstrate that ΔXT/FT N. benthamiana plants can be engineered toward the production of recombinant IgA1 with defined human-type N- and O-linked glycans. 26858738 7 19 theme core 1431:1434 arg1 O-glycans 1438:1446 disialylated mucin-type core 1 O-glycans 1407:1446 disialylated mucin-type core 1 O-glycans on plant-produced IgA1 1407:1469 By co-expression of enzymes required for initiation and elongation of human O-glycosylation it was possible to generate disialylated mucin-type core 1 O-glycans on plant-produced IgA1. 26858738 5 20 theme complex 918:924 arg1 N-glycans 938:946 complex biantennary N-glycans 918:946 complex biantennary N-glycans with terminal N-acetylglucosamine present on the N-glycosylation site of the CH2 domain in the IgA1 alpha chain 918:1058 Mass spectrometric analysis of IgA1 glycopeptides revealed the presence of complex biantennary N-glycans with terminal N-acetylglucosamine present on the N-glycosylation site of the CH2 domain in the IgA1 alpha chain. 26858738 5 21 theme N-glycans 938:946 arg1 presence 906:913 the presence 902:913 the presence of complex biantennary N-glycans with terminal N-acetylglucosamine present on the N-glycosylation site of the CH2 domain in the IgA1 alpha chain 902:1058 Mass spectrometric analysis of IgA1 glycopeptides revealed the presence of complex biantennary N-glycans with terminal N-acetylglucosamine present on the N-glycosylation site of the CH2 domain in the IgA1 alpha chain. 26858738 8 22 theme human-type 1600:1609 arg1 N- 1611:1612 defined human-type N- 1592:1612 defined human-type N- 1592:1612 Our data demonstrate that ΔXT/FT N. benthamiana plants can be engineered toward the production of recombinant IgA1 with defined human-type N- and O-linked glycans. 26858738 2 23 gly glycosylation 417:429 arg1 antibodies 393:402 recombinant monoclonal antibodies 370:402 recombinant monoclonal antibodies with defined glycosylation 370:429 The recent development of plant-based expression systems has demonstrated that plants are well-suited for the production of recombinant monoclonal antibodies with defined glycosylation. 26858738 4 24 theme * 766:766 arg1 antigen 778:784 the VP8* rotavirus antigen 759:784 the VP8* rotavirus antigen 759:784 Here, we transiently expressed recombinant human IgA1 against the VP8* rotavirus antigen in glyco-engineered ΔXT/FT Nicotiana benthamiana plants. 26858738 2 25 theme defined 409:415 arg1 glycosylation 417:429 defined glycosylation 409:429 defined glycosylation 409:429 The recent development of plant-based expression systems has demonstrated that plants are well-suited for the production of recombinant monoclonal antibodies with defined glycosylation. 26858738 7 26 gly disialylated 1407:1418 arg1 O-glycans 1438:1446 disialylated mucin-type core 1 O-glycans 1407:1446 disialylated mucin-type core 1 O-glycans on plant-produced IgA1 1407:1469 By co-expression of enzymes required for initiation and elongation of human O-glycosylation it was possible to generate disialylated mucin-type core 1 O-glycans on plant-produced IgA1. 26858738 5 27 theme domain 1029:1034 arg1 site 1013:1016 the N-glycosylation site 993:1016 the N-glycosylation site of the CH2 domain in the IgA1 alpha chain 993:1058 Mass spectrometric analysis of IgA1 glycopeptides revealed the presence of complex biantennary N-glycans with terminal N-acetylglucosamine present on the N-glycosylation site of the CH2 domain in the IgA1 alpha chain. 26858738 5 27 theme domain 1029:1034 arg1 domain 1029:1034 the CH2 domain 1021:1034 the CH2 domain 1021:1034 Mass spectrometric analysis of IgA1 glycopeptides revealed the presence of complex biantennary N-glycans with terminal N-acetylglucosamine present on the N-glycosylation site of the CH2 domain in the IgA1 alpha chain. 26858738 7 28 from O-glycans 1438:1446 arg1 IgA1 1466:1469 plant-produced IgA1 1451:1469 plant-produced IgA1 1451:1469 By co-expression of enzymes required for initiation and elongation of human O-glycosylation it was possible to generate disialylated mucin-type core 1 O-glycans on plant-produced IgA1. 26858738 7 29 theme mucin-type 1420:1429 arg1 O-glycans 1438:1446 disialylated mucin-type core 1 O-glycans 1407:1446 disialylated mucin-type core 1 O-glycans on plant-produced IgA1 1407:1469 By co-expression of enzymes required for initiation and elongation of human O-glycosylation it was possible to generate disialylated mucin-type core 1 O-glycans on plant-produced IgA1. 26858738 2 30 theme antibodies 393:402 arg1 production 356:365 the production 352:365 the production of recombinant monoclonal antibodies with defined glycosylation 352:429 The recent development of plant-based expression systems has demonstrated that plants are well-suited for the production of recombinant monoclonal antibodies with defined glycosylation. 26858738 0 31 theme Transient 0:8 arg1 Glyco-Engineering 10:26 Transient Glyco-Engineering 0:26 Transient Glyco-Engineering 0:26 Transient Glyco-Engineering to Produce Recombinant IgA1 with Defined N- and O-Glycans in Plants. 26858738 6 32 theme potential 1099:1107 arg1 sites 1125:1129 nine potential O-glycosylation sites 1094:1129 nine potential O-glycosylation sites 1094:1129 Analysis of the peptide carrying nine potential O-glycosylation sites in the IgA1 alpha chain hinge region showed the presence of plant-specific modifications including hydroxyproline formation and the attachment of pentoses. 26858738 6 33 theme peptide 1077:1083 arg1 Analysis 1061:1068 Analysis 1061:1068 Analysis of the peptide carrying nine potential O-glycosylation sites in the IgA1 alpha chain hinge region 1061:1166 Analysis of the peptide carrying nine potential O-glycosylation sites in the IgA1 alpha chain hinge region showed the presence of plant-specific modifications including hydroxyproline formation and the attachment of pentoses. 26858738 5 34 theme Mass 843:846 arg1 analysis 862:869 Mass spectrometric analysis 843:869 Mass spectrometric analysis of IgA1 glycopeptides 843:891 Mass spectrometric analysis of IgA1 glycopeptides revealed the presence of complex biantennary N-glycans with terminal N-acetylglucosamine present on the N-glycosylation site of the CH2 domain in the IgA1 alpha chain. 26858738 3 35 theme recombinant 631:641 arg1 biopharmaceuticals 643:660 novel recombinant biopharmaceuticals 625:660 novel recombinant biopharmaceuticals with enhanced anti-tumor activity 625:694 Compared to immunoglobulin G (IgG), less effort has been undertaken to express immunoglobulin A (IgA), which is the most prevalent antibody class at mucosal sites and a promising candidate for novel recombinant biopharmaceuticals with enhanced anti-tumor activity. 26858738 0 36 theme Recombinant 39:49 arg1 IgA1 51:54 Recombinant IgA1 39:54 Recombinant IgA1 with Defined N- and O-Glycans in Plants 39:94 Transient Glyco-Engineering to Produce Recombinant IgA1 with Defined N- and O-Glycans in Plants. 26858738 8 37 link O-linked 1618:1625 arg1 glycans 1627:1633 O-linked glycans 1618:1633 O-linked glycans 1618:1633 Our data demonstrate that ΔXT/FT N. benthamiana plants can be engineered toward the production of recombinant IgA1 with defined human-type N- and O-linked glycans. 26858738 8 38 theme ΔXT/FT 1498:1503 arg1 plants 1520:1525 ΔXT/FT N. benthamiana plants 1498:1525 ΔXT/FT N. benthamiana plants 1498:1525 Our data demonstrate that ΔXT/FT N. benthamiana plants can be engineered toward the production of recombinant IgA1 with defined human-type N- and O-linked glycans. 26858738 7 39 theme human 1357:1361 arg1 O-glycosylation 1363:1377 human O-glycosylation 1357:1377 human O-glycosylation 1357:1377 By co-expression of enzymes required for initiation and elongation of human O-glycosylation it was possible to generate disialylated mucin-type core 1 O-glycans on plant-produced IgA1. 26858738 3 40 theme anti-tumor 676:685 arg1 activity 687:694 enhanced anti-tumor activity 667:694 enhanced anti-tumor activity 667:694 Compared to immunoglobulin G (IgG), less effort has been undertaken to express immunoglobulin A (IgA), which is the most prevalent antibody class at mucosal sites and a promising candidate for novel recombinant biopharmaceuticals with enhanced anti-tumor activity. 26858738 4 41 theme glyco-engineered 789:804 arg1 plants 835:840 glyco-engineered ΔXT/FT Nicotiana benthamiana plants 789:840 glyco-engineered ΔXT/FT Nicotiana benthamiana plants 789:840 Here, we transiently expressed recombinant human IgA1 against the VP8* rotavirus antigen in glyco-engineered ΔXT/FT Nicotiana benthamiana plants. 26858738 5 42 from site 1013:1016 arg1 chain 1054:1058 the IgA1 alpha chain 1039:1058 the IgA1 alpha chain 1039:1058 Mass spectrometric analysis of IgA1 glycopeptides revealed the presence of complex biantennary N-glycans with terminal N-acetylglucosamine present on the N-glycosylation site of the CH2 domain in the IgA1 alpha chain. 26858738 6 43 theme hinge 1155:1159 arg1 region 1161:1166 the IgA1 alpha chain hinge region 1134:1166 the IgA1 alpha chain hinge region 1134:1166 Analysis of the peptide carrying nine potential O-glycosylation sites in the IgA1 alpha chain hinge region showed the presence of plant-specific modifications including hydroxyproline formation and the attachment of pentoses. 26858738 4 44 theme Nicotiana 813:821 arg1 plants 835:840 glyco-engineered ΔXT/FT Nicotiana benthamiana plants 789:840 glyco-engineered ΔXT/FT Nicotiana benthamiana plants 789:840 Here, we transiently expressed recombinant human IgA1 against the VP8* rotavirus antigen in glyco-engineered ΔXT/FT Nicotiana benthamiana plants. 26858738 2 45 theme recombinant 370:380 arg1 antibodies 393:402 recombinant monoclonal antibodies 370:402 recombinant monoclonal antibodies with defined glycosylation 370:429 The recent development of plant-based expression systems has demonstrated that plants are well-suited for the production of recombinant monoclonal antibodies with defined glycosylation. 26858738 2 46 with antibodies 393:402 arg1 glycosylation 417:429 defined glycosylation 409:429 defined glycosylation 409:429 The recent development of plant-based expression systems has demonstrated that plants are well-suited for the production of recombinant monoclonal antibodies with defined glycosylation. 26858738 5 47 theme alpha 1048:1052 arg1 chain 1054:1058 the IgA1 alpha chain 1039:1058 the IgA1 alpha chain 1039:1058 Mass spectrometric analysis of IgA1 glycopeptides revealed the presence of complex biantennary N-glycans with terminal N-acetylglucosamine present on the N-glycosylation site of the CH2 domain in the IgA1 alpha chain. 26858738 6 48 theme alpha 1143:1147 arg1 region 1161:1166 the IgA1 alpha chain hinge region 1134:1166 the IgA1 alpha chain hinge region 1134:1166 Analysis of the peptide carrying nine potential O-glycosylation sites in the IgA1 alpha chain hinge region showed the presence of plant-specific modifications including hydroxyproline formation and the attachment of pentoses. 26858738 5 49 attach present 982:988 arg1 site 1013:1016 the N-glycosylation site 993:1016 the N-glycosylation site of the CH2 domain in the IgA1 alpha chain 993:1058 Mass spectrometric analysis of IgA1 glycopeptides revealed the presence of complex biantennary N-glycans with terminal N-acetylglucosamine present on the N-glycosylation site of the CH2 domain in the IgA1 alpha chain. 26858738 5 49 attach present 982:988 arg2 N-acetylglucosamine 962:980 terminal N-acetylglucosamine 953:980 terminal N-acetylglucosamine present on the N-glycosylation site of the CH2 domain in the IgA1 alpha chain 953:1058 Mass spectrometric analysis of IgA1 glycopeptides revealed the presence of complex biantennary N-glycans with terminal N-acetylglucosamine present on the N-glycosylation site of the CH2 domain in the IgA1 alpha chain. 26858738 5 49 attach present 982:988 arg1 domain 1029:1034 the CH2 domain 1021:1034 the CH2 domain 1021:1034 Mass spectrometric analysis of IgA1 glycopeptides revealed the presence of complex biantennary N-glycans with terminal N-acetylglucosamine present on the N-glycosylation site of the CH2 domain in the IgA1 alpha chain. 26858738 5 50 gly glycopeptides 879:891 arg2 glycopeptides 879:891 IgA1 glycopeptides 874:891 IgA1 glycopeptides 874:891 Mass spectrometric analysis of IgA1 glycopeptides revealed the presence of complex biantennary N-glycans with terminal N-acetylglucosamine present on the N-glycosylation site of the CH2 domain in the IgA1 alpha chain. 26858738 2 51 theme expression 284:293 arg1 systems 295:301 plant-based expression systems 272:301 plant-based expression systems 272:301 The recent development of plant-based expression systems has demonstrated that plants are well-suited for the production of recombinant monoclonal antibodies with defined glycosylation. 26858738 5 52 theme glycopeptides 879:891 arg1 analysis 862:869 Mass spectrometric analysis 843:869 Mass spectrometric analysis of IgA1 glycopeptides 843:891 Mass spectrometric analysis of IgA1 glycopeptides revealed the presence of complex biantennary N-glycans with terminal N-acetylglucosamine present on the N-glycosylation site of the CH2 domain in the IgA1 alpha chain. 26858738 6 53 theme plant-specific 1191:1204 arg1 modifications 1206:1218 plant-specific modifications 1191:1218 plant-specific modifications including hydroxyproline formation and the attachment of pentoses 1191:1284 Analysis of the peptide carrying nine potential O-glycosylation sites in the IgA1 alpha chain hinge region showed the presence of plant-specific modifications including hydroxyproline formation and the attachment of pentoses. 26858738 6 53 theme plant-specific 1191:1204 arg1 formation 1245:1253 hydroxyproline formation 1230:1253 hydroxyproline formation 1230:1253 Analysis of the peptide carrying nine potential O-glycosylation sites in the IgA1 alpha chain hinge region showed the presence of plant-specific modifications including hydroxyproline formation and the attachment of pentoses. 26858738 6 53 theme plant-specific 1191:1204 arg1 attachment 1263:1272 the attachment 1259:1272 the attachment of pentoses 1259:1284 Analysis of the peptide carrying nine potential O-glycosylation sites in the IgA1 alpha chain hinge region showed the presence of plant-specific modifications including hydroxyproline formation and the attachment of pentoses. 26858738 5 54 theme spectrometric 848:860 arg1 analysis 862:869 Mass spectrometric analysis 843:869 Mass spectrometric analysis of IgA1 glycopeptides 843:891 Mass spectrometric analysis of IgA1 glycopeptides revealed the presence of complex biantennary N-glycans with terminal N-acetylglucosamine present on the N-glycosylation site of the CH2 domain in the IgA1 alpha chain. 26858738 3 55 theme antibody 563:570 arg1 A 526:526 immunoglobulin A 511:526 immunoglobulin A (IgA) 511:532 Compared to immunoglobulin G (IgG), less effort has been undertaken to express immunoglobulin A (IgA), which is the most prevalent antibody class at mucosal sites and a promising candidate for novel recombinant biopharmaceuticals with enhanced anti-tumor activity. 26858738 3 55 theme antibody 563:570 arg1 class 572:576 the most prevalent antibody class 544:576 the most prevalent antibody class at mucosal sites 544:593 Compared to immunoglobulin G (IgG), less effort has been undertaken to express immunoglobulin A (IgA), which is the most prevalent antibody class at mucosal sites and a promising candidate for novel recombinant biopharmaceuticals with enhanced anti-tumor activity. 26858738 8 56 theme benthamiana 1508:1518 arg1 plants 1520:1525 ΔXT/FT N. benthamiana plants 1498:1525 ΔXT/FT N. benthamiana plants 1498:1525 Our data demonstrate that ΔXT/FT N. benthamiana plants can be engineered toward the production of recombinant IgA1 with defined human-type N- and O-linked glycans. 26858738 2 57 theme recent 250:255 arg1 development 257:267 The recent development 246:267 The recent development of plant-based expression systems 246:301 The recent development of plant-based expression systems has demonstrated that plants are well-suited for the production of recombinant monoclonal antibodies with defined glycosylation. 26858738 1 58 theme antibodies 127:136 arg1 production 101:110 The production 97:110 The production of therapeutic antibodies to combat pathogens and treat diseases, such as cancer 97:191 The production of therapeutic antibodies to combat pathogens and treat diseases, such as cancer is of great interest for the biotechnology industry. 26858738 8 59 theme IgA1 1582:1585 arg1 production 1556:1565 the production 1552:1565 the production of recombinant IgA1 with defined human-type N- and O-linked glycans 1552:1633 Our data demonstrate that ΔXT/FT N. benthamiana plants can be engineered toward the production of recombinant IgA1 with defined human-type N- and O-linked glycans. 26858738 8 60 theme defined 1592:1598 arg1 N- 1611:1612 defined human-type N- 1592:1612 defined human-type N- 1592:1612 Our data demonstrate that ΔXT/FT N. benthamiana plants can be engineered toward the production of recombinant IgA1 with defined human-type N- and O-linked glycans. 26858738 5 61 theme biantennary 926:936 arg1 N-glycans 938:946 complex biantennary N-glycans 918:946 complex biantennary N-glycans with terminal N-acetylglucosamine present on the N-glycosylation site of the CH2 domain in the IgA1 alpha chain 918:1058 Mass spectrometric analysis of IgA1 glycopeptides revealed the presence of complex biantennary N-glycans with terminal N-acetylglucosamine present on the N-glycosylation site of the CH2 domain in the IgA1 alpha chain. 26858738 5 62 with N-glycans 938:946 arg1 N-acetylglucosamine 962:980 terminal N-acetylglucosamine 953:980 terminal N-acetylglucosamine present on the N-glycosylation site of the CH2 domain in the IgA1 alpha chain 953:1058 Mass spectrometric analysis of IgA1 glycopeptides revealed the presence of complex biantennary N-glycans with terminal N-acetylglucosamine present on the N-glycosylation site of the CH2 domain in the IgA1 alpha chain. 26858738 8 63 theme O-linked 1618:1625 arg1 glycans 1627:1633 O-linked glycans 1618:1633 O-linked glycans 1618:1633 Our data demonstrate that ΔXT/FT N. benthamiana plants can be engineered toward the production of recombinant IgA1 with defined human-type N- and O-linked glycans. 26858738 4 64 theme VP8 763:765 arg1 * 766:766 VP8* 763:766 the VP8* rotavirus antigen 759:784 Here, we transiently expressed recombinant human IgA1 against the VP8* rotavirus antigen in glyco-engineered ΔXT/FT Nicotiana benthamiana plants. 26858738 3 65 from sites 589:593 arg1 candidate 611:619 a promising candidate 599:619 a promising candidate for novel recombinant biopharmaceuticals with enhanced anti-tumor activity 599:694 Compared to immunoglobulin G (IgG), less effort has been undertaken to express immunoglobulin A (IgA), which is the most prevalent antibody class at mucosal sites and a promising candidate for novel recombinant biopharmaceuticals with enhanced anti-tumor activity. 26858738 3 65 from sites 589:593 arg1 A 526:526 immunoglobulin A 511:526 immunoglobulin A (IgA) 511:532 Compared to immunoglobulin G (IgG), less effort has been undertaken to express immunoglobulin A (IgA), which is the most prevalent antibody class at mucosal sites and a promising candidate for novel recombinant biopharmaceuticals with enhanced anti-tumor activity. 26858738 3 65 from sites 589:593 arg1 class 572:576 the most prevalent antibody class 544:576 the most prevalent antibody class at mucosal sites 544:593 Compared to immunoglobulin G (IgG), less effort has been undertaken to express immunoglobulin A (IgA), which is the most prevalent antibody class at mucosal sites and a promising candidate for novel recombinant biopharmaceuticals with enhanced anti-tumor activity. 26858738 5 66 theme CH2 1025:1027 arg1 domain 1029:1034 the CH2 domain 1021:1034 the CH2 domain 1021:1034 Mass spectrometric analysis of IgA1 glycopeptides revealed the presence of complex biantennary N-glycans with terminal N-acetylglucosamine present on the N-glycosylation site of the CH2 domain in the IgA1 alpha chain. 26858738 7 67 theme disialylated 1407:1418 arg1 O-glycans 1438:1446 disialylated mucin-type core 1 O-glycans 1407:1446 disialylated mucin-type core 1 O-glycans on plant-produced IgA1 1407:1469 By co-expression of enzymes required for initiation and elongation of human O-glycosylation it was possible to generate disialylated mucin-type core 1 O-glycans on plant-produced IgA1. 26858738 5 68 gly N-glycosylation 997:1011 arg2 domain 1029:1034 the CH2 domain 1021:1034 the CH2 domain 1021:1034 Mass spectrometric analysis of IgA1 glycopeptides revealed the presence of complex biantennary N-glycans with terminal N-acetylglucosamine present on the N-glycosylation site of the CH2 domain in the IgA1 alpha chain. 26858738 5 68 gly N-glycosylation 997:1011 arg2 site 1013:1016 the N-glycosylation site 993:1016 the N-glycosylation site of the CH2 domain in the IgA1 alpha chain 993:1058 Mass spectrometric analysis of IgA1 glycopeptides revealed the presence of complex biantennary N-glycans with terminal N-acetylglucosamine present on the N-glycosylation site of the CH2 domain in the IgA1 alpha chain. 26858738 5 68 gly N-glycosylation 997:1011 arg1 domain 1029:1034 the CH2 domain 1021:1034 the CH2 domain 1021:1034 Mass spectrometric analysis of IgA1 glycopeptides revealed the presence of complex biantennary N-glycans with terminal N-acetylglucosamine present on the N-glycosylation site of the CH2 domain in the IgA1 alpha chain. 26858738 0 69 from IgA1 51:54 arg1 Plants 89:94 Plants 89:94 Plants 89:94 Transient Glyco-Engineering to Produce Recombinant IgA1 with Defined N- and O-Glycans in Plants. 26858738 4 70 theme rotavirus 768:776 arg1 antigen 778:784 the VP8* rotavirus antigen 759:784 the VP8* rotavirus antigen 759:784 Here, we transiently expressed recombinant human IgA1 against the VP8* rotavirus antigen in glyco-engineered ΔXT/FT Nicotiana benthamiana plants. 26858738 6 71 theme O-glycosylation 1109:1123 arg1 sites 1125:1129 nine potential O-glycosylation sites 1094:1129 nine potential O-glycosylation sites 1094:1129 Analysis of the peptide carrying nine potential O-glycosylation sites in the IgA1 alpha chain hinge region showed the presence of plant-specific modifications including hydroxyproline formation and the attachment of pentoses. 26858738 4 72 theme human 740:744 arg1 IgA1 746:749 recombinant human IgA1 728:749 recombinant human IgA1 against the VP8* rotavirus antigen 728:784 Here, we transiently expressed recombinant human IgA1 against the VP8* rotavirus antigen in glyco-engineered ΔXT/FT Nicotiana benthamiana plants. 26858738 2 73 theme monoclonal 382:391 arg1 antibodies 393:402 recombinant monoclonal antibodies 370:402 recombinant monoclonal antibodies with defined glycosylation 370:429 The recent development of plant-based expression systems has demonstrated that plants are well-suited for the production of recombinant monoclonal antibodies with defined glycosylation. 26858738 5 74 theme N-glycosylation 997:1011 arg1 site 1013:1016 the N-glycosylation site 993:1016 the N-glycosylation site of the CH2 domain in the IgA1 alpha chain 993:1058 Mass spectrometric analysis of IgA1 glycopeptides revealed the presence of complex biantennary N-glycans with terminal N-acetylglucosamine present on the N-glycosylation site of the CH2 domain in the IgA1 alpha chain. 26858738 5 74 theme N-glycosylation 997:1011 arg1 domain 1029:1034 the CH2 domain 1021:1034 the CH2 domain 1021:1034 Mass spectrometric analysis of IgA1 glycopeptides revealed the presence of complex biantennary N-glycans with terminal N-acetylglucosamine present on the N-glycosylation site of the CH2 domain in the IgA1 alpha chain. 26858738 3 75 theme novel 625:629 arg1 biopharmaceuticals 643:660 novel recombinant biopharmaceuticals 625:660 novel recombinant biopharmaceuticals with enhanced anti-tumor activity 625:694 Compared to immunoglobulin G (IgG), less effort has been undertaken to express immunoglobulin A (IgA), which is the most prevalent antibody class at mucosal sites and a promising candidate for novel recombinant biopharmaceuticals with enhanced anti-tumor activity. 26858738 8 76 with IgA1 1582:1585 arg1 N- 1611:1612 defined human-type N- 1592:1612 defined human-type N- 1592:1612 Our data demonstrate that ΔXT/FT N. benthamiana plants can be engineered toward the production of recombinant IgA1 with defined human-type N- and O-linked glycans. 26858738 8 76 with IgA1 1582:1585 arg1 glycans 1627:1633 O-linked glycans 1618:1633 O-linked glycans 1618:1633 Our data demonstrate that ΔXT/FT N. benthamiana plants can be engineered toward the production of recombinant IgA1 with defined human-type N- and O-linked glycans. 26858738 7 77 theme O-glycosylation 1363:1377 arg1 elongation 1343:1352 elongation 1343:1352 elongation 1343:1352 By co-expression of enzymes required for initiation and elongation of human O-glycosylation it was possible to generate disialylated mucin-type core 1 O-glycans on plant-produced IgA1. 26858738 7 77 theme O-glycosylation 1363:1377 arg1 initiation 1328:1337 initiation 1328:1337 initiation 1328:1337 By co-expression of enzymes required for initiation and elongation of human O-glycosylation it was possible to generate disialylated mucin-type core 1 O-glycans on plant-produced IgA1. 26858738 4 78 theme benthamiana 823:833 arg1 plants 835:840 glyco-engineered ΔXT/FT Nicotiana benthamiana plants 789:840 glyco-engineered ΔXT/FT Nicotiana benthamiana plants 789:840 Here, we transiently expressed recombinant human IgA1 against the VP8* rotavirus antigen in glyco-engineered ΔXT/FT Nicotiana benthamiana plants. 26858738 0 79 theme Defined 61:67 arg1 N- 69:70 N- 69:70 N- 69:70 Transient Glyco-Engineering to Produce Recombinant IgA1 with Defined N- and O-Glycans in Plants. 26858738 6 80 contain carrying 1085:1092 arg2 sites 1125:1129 nine potential O-glycosylation sites 1094:1129 nine potential O-glycosylation sites 1094:1129 Analysis of the peptide carrying nine potential O-glycosylation sites in the IgA1 alpha chain hinge region showed the presence of plant-specific modifications including hydroxyproline formation and the attachment of pentoses. 26858738 6 80 contain carrying 1085:1092 arg1 peptide 1077:1083 the peptide 1073:1083 the peptide carrying nine potential O-glycosylation sites in the IgA1 alpha chain hinge region 1073:1166 Analysis of the peptide carrying nine potential O-glycosylation sites in the IgA1 alpha chain hinge region showed the presence of plant-specific modifications including hydroxyproline formation and the attachment of pentoses. 26858738 3 81 theme enhanced 667:674 arg1 activity 687:694 enhanced anti-tumor activity 667:694 enhanced anti-tumor activity 667:694 Compared to immunoglobulin G (IgG), less effort has been undertaken to express immunoglobulin A (IgA), which is the most prevalent antibody class at mucosal sites and a promising candidate for novel recombinant biopharmaceuticals with enhanced anti-tumor activity. 26858738 6 82 gly O-glycosylation 1109:1123 arg2 sites 1125:1129 nine potential O-glycosylation sites 1094:1129 nine potential O-glycosylation sites 1094:1129 Analysis of the peptide carrying nine potential O-glycosylation sites in the IgA1 alpha chain hinge region showed the presence of plant-specific modifications including hydroxyproline formation and the attachment of pentoses. 26858738 6 82 gly O-glycosylation 1109:1123 arg2 nine 1094:1097 nine 1094:1097 nine 1094:1097 Analysis of the peptide carrying nine potential O-glycosylation sites in the IgA1 alpha chain hinge region showed the presence of plant-specific modifications including hydroxyproline formation and the attachment of pentoses. 26858738 8 83 theme N. 1505:1506 arg1 plants 1520:1525 ΔXT/FT N. benthamiana plants 1498:1525 ΔXT/FT N. benthamiana plants 1498:1525 Our data demonstrate that ΔXT/FT N. benthamiana plants can be engineered toward the production of recombinant IgA1 with defined human-type N- and O-linked glycans. 26858738 5 84 theme IgA1 874:877 arg1 glycopeptides 879:891 IgA1 glycopeptides 874:891 IgA1 glycopeptides 874:891 Mass spectrometric analysis of IgA1 glycopeptides revealed the presence of complex biantennary N-glycans with terminal N-acetylglucosamine present on the N-glycosylation site of the CH2 domain in the IgA1 alpha chain. 26858738 5 85 theme IgA1 1043:1046 arg1 chain 1054:1058 the IgA1 alpha chain 1039:1058 the IgA1 alpha chain 1039:1058 Mass spectrometric analysis of IgA1 glycopeptides revealed the presence of complex biantennary N-glycans with terminal N-acetylglucosamine present on the N-glycosylation site of the CH2 domain in the IgA1 alpha chain. 26858738 6 86 theme chain 1149:1153 arg1 region 1161:1166 the IgA1 alpha chain hinge region 1134:1166 the IgA1 alpha chain hinge region 1134:1166 Analysis of the peptide carrying nine potential O-glycosylation sites in the IgA1 alpha chain hinge region showed the presence of plant-specific modifications including hydroxyproline formation and the attachment of pentoses. 26858738 4 87 theme ΔXT/FT 806:811 arg1 plants 835:840 glyco-engineered ΔXT/FT Nicotiana benthamiana plants 789:840 glyco-engineered ΔXT/FT Nicotiana benthamiana plants 789:840 Here, we transiently expressed recombinant human IgA1 against the VP8* rotavirus antigen in glyco-engineered ΔXT/FT Nicotiana benthamiana plants. 26858738 0 88 with IgA1 51:54 arg1 O-Glycans 76:84 O-Glycans 76:84 O-Glycans 76:84 Transient Glyco-Engineering to Produce Recombinant IgA1 with Defined N- and O-Glycans in Plants. 26858738 0 88 with IgA1 51:54 arg1 N- 69:70 N- 69:70 N- 69:70 Transient Glyco-Engineering to Produce Recombinant IgA1 with Defined N- and O-Glycans in Plants. 26858738 7 89 theme enzymes 1307:1313 arg1 co-expression 1290:1302 co-expression 1290:1302 co-expression of enzymes required for initiation and elongation of human O-glycosylation 1290:1377 By co-expression of enzymes required for initiation and elongation of human O-glycosylation it was possible to generate disialylated mucin-type core 1 O-glycans on plant-produced IgA1. 26858738 1 90 theme biotechnology 222:234 arg1 industry 236:243 the biotechnology industry 218:243 the biotechnology industry 218:243 The production of therapeutic antibodies to combat pathogens and treat diseases, such as cancer is of great interest for the biotechnology industry. 28584151 4 0 theme proteins 643:650 arg1 panel 613:617 a panel 611:617 a panel of 124 envelope (gp160) proteins spanning 11 subtypes 611:671 The final optimized inhibitor exhibited full potency against a panel of 124 envelope (gp160) proteins spanning 11 subtypes, indicating broad-spectrum activity. 28584151 3 1 theme mRNA 462:465 arg1 display 467:473 mRNA display 462:473 mRNA display 462:473 The progenitor sequence of this novel inhibitor was selected from a library of trillions of Adnectin variants using mRNA display and then further optimized for improved antiviral and physical properties. 28584151 0 2 theme Anti-HIV 75:82 arg1 Activity 84:91 Potent Anti-HIV Activity 68:91 Potent Anti-HIV Activity 68:91 Discovery and Characterization of a Novel CD4-Binding Adnectin with Potent Anti-HIV Activity. 28584151 5 3 theme viral 855:859 arg1 titer 861:865 viral titer 855:865 viral titer breakthrough 855:878 Resistance profiling studies showed that this inhibitor required 30 passages (151 days) in culture to acquire sufficient resistance to result in viral titer breakthrough. 28584151 4 4 theme optimized 560:568 arg1 inhibitor 570:578 The final optimized inhibitor 550:578 The final optimized inhibitor 550:578 The final optimized inhibitor exhibited full potency against a panel of 124 envelope (gp160) proteins spanning 11 subtypes, indicating broad-spectrum activity. 28584151 3 5 theme antiviral 515:523 arg1 properties 538:547 improved antiviral and physical properties 506:547 improved antiviral and physical properties 506:547 The progenitor sequence of this novel inhibitor was selected from a library of trillions of Adnectin variants using mRNA display and then further optimized for improved antiviral and physical properties. 28584151 3 6 theme improved 506:513 arg1 properties 538:547 improved antiviral and physical properties 506:547 improved antiviral and physical properties 506:547 The progenitor sequence of this novel inhibitor was selected from a library of trillions of Adnectin variants using mRNA display and then further optimized for improved antiviral and physical properties. 28584151 4 7 theme final 554:558 arg1 inhibitor 570:578 The final optimized inhibitor 550:578 The final optimized inhibitor 550:578 The final optimized inhibitor exhibited full potency against a panel of 124 envelope (gp160) proteins spanning 11 subtypes, indicating broad-spectrum activity. 28584151 5 8 theme Resistance 710:719 arg1 studies 731:737 Resistance profiling studies 710:737 Resistance profiling studies 710:737 Resistance profiling studies showed that this inhibitor required 30 passages (151 days) in culture to acquire sufficient resistance to result in viral titer breakthrough. 28584151 2 9 theme CD4 300:302 arg1 engagement 304:313 CD4 engagement 300:313 CD4 engagement 300:313 This inhibitor binds to human CD4 with a high affinity (3.9 nM) and inhibits viral entry at a step after CD4 engagement and preceding membrane fusion. 28584151 6 10 from gp120 965:969 arg1 loss 906:909 the loss 902:909 the loss of multiple potential N-linked glycosylation sites in gp120 902:969 Resistance mapped to the loss of multiple potential N-linked glycosylation sites in gp120, suggesting that inhibition is due to steric hindrance of CD4-binding-induced conformational changes. 28584151 3 11 theme trillions 425:433 arg1 library 414:420 a library 412:420 a library of trillions of Adnectin variants 412:454 The progenitor sequence of this novel inhibitor was selected from a library of trillions of Adnectin variants using mRNA display and then further optimized for improved antiviral and physical properties. 28584151 4 12 theme gp160 636:640 arg1 proteins 643:650 124 envelope (gp160) proteins 622:650 124 envelope (gp160) proteins spanning 11 subtypes 622:671 The final optimized inhibitor exhibited full potency against a panel of 124 envelope (gp160) proteins spanning 11 subtypes, indicating broad-spectrum activity. 28584151 4 13 theme envelope 626:633 arg1 proteins 643:650 124 envelope (gp160) proteins 622:650 124 envelope (gp160) proteins spanning 11 subtypes 622:671 The final optimized inhibitor exhibited full potency against a panel of 124 envelope (gp160) proteins spanning 11 subtypes, indicating broad-spectrum activity. 28584151 5 14 theme profiling 721:729 arg1 studies 731:737 Resistance profiling studies 710:737 Resistance profiling studies 710:737 Resistance profiling studies showed that this inhibitor required 30 passages (151 days) in culture to acquire sufficient resistance to result in viral titer breakthrough. 28584151 6 15 gly glycosylation 942:954 arg2 sites 956:960 multiple potential N-linked glycosylation sites 914:960 multiple potential N-linked glycosylation sites in gp120 914:969 Resistance mapped to the loss of multiple potential N-linked glycosylation sites in gp120, suggesting that inhibition is due to steric hindrance of CD4-binding-induced conformational changes. 28584151 3 16 theme variants 447:454 arg1 trillions 425:433 trillions 425:433 trillions of Adnectin variants 425:454 The progenitor sequence of this novel inhibitor was selected from a library of trillions of Adnectin variants using mRNA display and then further optimized for improved antiviral and physical properties. 28584151 1 17 theme in 175:176 arg1 selection 184:192 in vitro selection 175:192 in vitro selection 175:192 A novel fibronectin-based protein (Adnectin) HIV-1 inhibitor was generated using in vitro selection. 28584151 3 18 theme physical 529:536 arg1 properties 538:547 improved antiviral and physical properties 506:547 improved antiviral and physical properties 506:547 The progenitor sequence of this novel inhibitor was selected from a library of trillions of Adnectin variants using mRNA display and then further optimized for improved antiviral and physical properties. 28584151 3 19 theme inhibitor 384:392 arg1 sequence 361:368 The progenitor sequence 346:368 The progenitor sequence of this novel inhibitor 346:392 The progenitor sequence of this novel inhibitor was selected from a library of trillions of Adnectin variants using mRNA display and then further optimized for improved antiviral and physical properties. 28584151 3 20 theme progenitor 350:359 arg1 sequence 361:368 The progenitor sequence 346:368 The progenitor sequence of this novel inhibitor 346:392 The progenitor sequence of this novel inhibitor was selected from a library of trillions of Adnectin variants using mRNA display and then further optimized for improved antiviral and physical properties. 28584151 6 21 theme sites 956:960 arg1 loss 906:909 the loss 902:909 the loss of multiple potential N-linked glycosylation sites in gp120 902:969 Resistance mapped to the loss of multiple potential N-linked glycosylation sites in gp120, suggesting that inhibition is due to steric hindrance of CD4-binding-induced conformational changes. 28584151 5 22 theme sufficient 820:829 arg1 resistance 831:840 sufficient resistance 820:840 sufficient resistance 820:840 Resistance profiling studies showed that this inhibitor required 30 passages (151 days) in culture to acquire sufficient resistance to result in viral titer breakthrough. 28584151 6 23 theme CD4-binding-induced 1029:1047 arg1 changes 1064:1070 CD4-binding-induced conformational changes 1029:1070 CD4-binding-induced conformational changes 1029:1070 Resistance mapped to the loss of multiple potential N-linked glycosylation sites in gp120, suggesting that inhibition is due to steric hindrance of CD4-binding-induced conformational changes. 28584151 6 24 theme glycosylation 942:954 arg1 sites 956:960 multiple potential N-linked glycosylation sites 914:960 multiple potential N-linked glycosylation sites in gp120 914:969 Resistance mapped to the loss of multiple potential N-linked glycosylation sites in gp120, suggesting that inhibition is due to steric hindrance of CD4-binding-induced conformational changes. 28584151 2 25 theme viral 272:276 arg1 entry 278:282 viral entry 272:282 viral entry 272:282 This inhibitor binds to human CD4 with a high affinity (3.9 nM) and inhibits viral entry at a step after CD4 engagement and preceding membrane fusion. 28584151 6 26 theme changes 1064:1070 arg1 hindrance 1016:1024 steric hindrance 1009:1024 steric hindrance of CD4-binding-induced conformational changes 1009:1070 Resistance mapped to the loss of multiple potential N-linked glycosylation sites in gp120, suggesting that inhibition is due to steric hindrance of CD4-binding-induced conformational changes. 28584151 6 27 theme N-linked 933:940 arg1 sites 956:960 multiple potential N-linked glycosylation sites 914:960 multiple potential N-linked glycosylation sites in gp120 914:969 Resistance mapped to the loss of multiple potential N-linked glycosylation sites in gp120, suggesting that inhibition is due to steric hindrance of CD4-binding-induced conformational changes. 28584151 1 28 theme fibronectin-based 102:118 arg1 inhibitor 145:153 A novel fibronectin-based protein (Adnectin) HIV-1 inhibitor 94:153 A novel fibronectin-based protein (Adnectin) HIV-1 inhibitor 94:153 A novel fibronectin-based protein (Adnectin) HIV-1 inhibitor was generated using in vitro selection. 28584151 1 29 theme HIV-1 139:143 arg1 inhibitor 145:153 A novel fibronectin-based protein (Adnectin) HIV-1 inhibitor 94:153 A novel fibronectin-based protein (Adnectin) HIV-1 inhibitor 94:153 A novel fibronectin-based protein (Adnectin) HIV-1 inhibitor was generated using in vitro selection. 28584151 0 30 theme Novel 36:40 arg1 Adnectin 54:61 a Novel CD4-Binding Adnectin 34:61 a Novel CD4-Binding Adnectin with Potent Anti-HIV Activity 34:91 Discovery and Characterization of a Novel CD4-Binding Adnectin with Potent Anti-HIV Activity. 28584151 6 31 theme potential 923:931 arg1 sites 956:960 multiple potential N-linked glycosylation sites 914:960 multiple potential N-linked glycosylation sites in gp120 914:969 Resistance mapped to the loss of multiple potential N-linked glycosylation sites in gp120, suggesting that inhibition is due to steric hindrance of CD4-binding-induced conformational changes. 28584151 6 32 from sites 956:960 arg1 gp120 965:969 gp120 965:969 gp120 965:969 Resistance mapped to the loss of multiple potential N-linked glycosylation sites in gp120, suggesting that inhibition is due to steric hindrance of CD4-binding-induced conformational changes. 28584151 6 33 link N-linked 933:940 arg1 sites 956:960 multiple potential N-linked glycosylation sites 914:960 multiple potential N-linked glycosylation sites in gp120 914:969 Resistance mapped to the loss of multiple potential N-linked glycosylation sites in gp120, suggesting that inhibition is due to steric hindrance of CD4-binding-induced conformational changes. 28584151 6 34 theme steric 1009:1014 arg1 hindrance 1016:1024 steric hindrance 1009:1024 steric hindrance of CD4-binding-induced conformational changes 1009:1070 Resistance mapped to the loss of multiple potential N-linked glycosylation sites in gp120, suggesting that inhibition is due to steric hindrance of CD4-binding-induced conformational changes. 28584151 3 35 theme novel 378:382 arg1 inhibitor 384:392 this novel inhibitor 373:392 this novel inhibitor 373:392 The progenitor sequence of this novel inhibitor was selected from a library of trillions of Adnectin variants using mRNA display and then further optimized for improved antiviral and physical properties. 28584151 6 36 theme multiple 914:921 arg1 sites 956:960 multiple potential N-linked glycosylation sites 914:960 multiple potential N-linked glycosylation sites in gp120 914:969 Resistance mapped to the loss of multiple potential N-linked glycosylation sites in gp120, suggesting that inhibition is due to steric hindrance of CD4-binding-induced conformational changes. 28584151 6 37 theme conformational 1049:1062 arg1 changes 1064:1070 CD4-binding-induced conformational changes 1029:1070 CD4-binding-induced conformational changes 1029:1070 Resistance mapped to the loss of multiple potential N-linked glycosylation sites in gp120, suggesting that inhibition is due to steric hindrance of CD4-binding-induced conformational changes. 28584151 0 38 theme Adnectin 54:61 arg1 Characterization 14:29 Characterization 14:29 Characterization 14:29 Discovery and Characterization of a Novel CD4-Binding Adnectin with Potent Anti-HIV Activity. 28584151 0 38 theme Adnectin 54:61 arg1 Discovery 0:8 Discovery 0:8 Discovery 0:8 Discovery and Characterization of a Novel CD4-Binding Adnectin with Potent Anti-HIV Activity. 28584151 6 39 from loss 906:909 arg1 gp120 965:969 gp120 965:969 gp120 965:969 Resistance mapped to the loss of multiple potential N-linked glycosylation sites in gp120, suggesting that inhibition is due to steric hindrance of CD4-binding-induced conformational changes. 28584151 2 40 theme human 219:223 arg1 CD4 225:227 human CD4 219:227 human CD4 219:227 This inhibitor binds to human CD4 with a high affinity (3.9 nM) and inhibits viral entry at a step after CD4 engagement and preceding membrane fusion. 28584151 1 41 theme protein 120:126 arg1 inhibitor 145:153 A novel fibronectin-based protein (Adnectin) HIV-1 inhibitor 94:153 A novel fibronectin-based protein (Adnectin) HIV-1 inhibitor 94:153 A novel fibronectin-based protein (Adnectin) HIV-1 inhibitor was generated using in vitro selection. 28584151 0 42 theme CD4-Binding 42:52 arg1 Adnectin 54:61 a Novel CD4-Binding Adnectin 34:61 a Novel CD4-Binding Adnectin with Potent Anti-HIV Activity 34:91 Discovery and Characterization of a Novel CD4-Binding Adnectin with Potent Anti-HIV Activity. 28584151 1 43 dep in 175:176 arg1 vitro 178:182 vitro 178:182 vitro 178:182 A novel fibronectin-based protein (Adnectin) HIV-1 inhibitor was generated using in vitro selection. 28584151 5 44 from passages 778:785 arg1 culture 801:807 culture 801:807 culture 801:807 Resistance profiling studies showed that this inhibitor required 30 passages (151 days) in culture to acquire sufficient resistance to result in viral titer breakthrough. 28584151 1 45 theme Adnectin 129:136 arg1 inhibitor 145:153 A novel fibronectin-based protein (Adnectin) HIV-1 inhibitor 94:153 A novel fibronectin-based protein (Adnectin) HIV-1 inhibitor 94:153 A novel fibronectin-based protein (Adnectin) HIV-1 inhibitor was generated using in vitro selection. 28584151 1 46 theme novel 96:100 arg1 inhibitor 145:153 A novel fibronectin-based protein (Adnectin) HIV-1 inhibitor 94:153 A novel fibronectin-based protein (Adnectin) HIV-1 inhibitor 94:153 A novel fibronectin-based protein (Adnectin) HIV-1 inhibitor was generated using in vitro selection. 28584151 0 47 with Adnectin 54:61 arg1 Activity 84:91 Potent Anti-HIV Activity 68:91 Potent Anti-HIV Activity 68:91 Discovery and Characterization of a Novel CD4-Binding Adnectin with Potent Anti-HIV Activity. 28584151 3 48 theme Adnectin 438:445 arg1 variants 447:454 Adnectin variants 438:454 Adnectin variants 438:454 The progenitor sequence of this novel inhibitor was selected from a library of trillions of Adnectin variants using mRNA display and then further optimized for improved antiviral and physical properties. 28584151 4 49 theme broad-spectrum 685:698 arg1 activity 700:707 broad-spectrum activity 685:707 broad-spectrum activity 685:707 The final optimized inhibitor exhibited full potency against a panel of 124 envelope (gp160) proteins spanning 11 subtypes, indicating broad-spectrum activity. 28584151 0 50 theme Potent 68:73 arg1 Activity 84:91 Potent Anti-HIV Activity 68:91 Potent Anti-HIV Activity 68:91 Discovery and Characterization of a Novel CD4-Binding Adnectin with Potent Anti-HIV Activity. 28584151 2 51 theme high 236:239 arg1 affinity 241:248 a high affinity 234:248 a high affinity (3.9 nM) 234:257 This inhibitor binds to human CD4 with a high affinity (3.9 nM) and inhibits viral entry at a step after CD4 engagement and preceding membrane fusion. 28584151 2 51 theme high 236:239 arg1 nM 255:256 3.9 nM 251:256 3.9 nM 251:256 This inhibitor binds to human CD4 with a high affinity (3.9 nM) and inhibits viral entry at a step after CD4 engagement and preceding membrane fusion. 28584151 2 52 theme membrane 329:336 arg1 fusion 338:343 preceding membrane fusion 319:343 preceding membrane fusion 319:343 This inhibitor binds to human CD4 with a high affinity (3.9 nM) and inhibits viral entry at a step after CD4 engagement and preceding membrane fusion. 28584151 4 53 theme 124 622:624 arg1 proteins 643:650 124 envelope (gp160) proteins 622:650 124 envelope (gp160) proteins spanning 11 subtypes 622:671 The final optimized inhibitor exhibited full potency against a panel of 124 envelope (gp160) proteins spanning 11 subtypes, indicating broad-spectrum activity. 28584151 2 54 theme preceding 319:327 arg1 fusion 338:343 preceding membrane fusion 319:343 preceding membrane fusion 319:343 This inhibitor binds to human CD4 with a high affinity (3.9 nM) and inhibits viral entry at a step after CD4 engagement and preceding membrane fusion. 28584151 4 55 theme full 590:593 arg1 potency 595:601 full potency 590:601 full potency 590:601 The final optimized inhibitor exhibited full potency against a panel of 124 envelope (gp160) proteins spanning 11 subtypes, indicating broad-spectrum activity. 25525276 8 0 theme novel 1326:1330 arg1 information 1332:1342 novel information 1326:1342 novel information on the mechanisms behind the influence of SorLA activity on APP metabolism 1326:1417 Our results provide novel information on the mechanisms behind the influence of SorLA activity on APP metabolism by controlling post-translational glycosylation in the Golgi, suggesting new strategies against amyloidogenesis in Alzheimer disease. 25525276 2 1 theme peptide 349:355 arg1 generation 321:330 a decreased generation 309:330 a decreased generation of the amyloid-β peptide 309:355 SorLA interacts directly with the amyloid precursor protein (APP) and affects the processing of the precursor, leading to a decreased generation of the amyloid-β peptide. 25525276 7 2 link O-linked 1243:1250 arg1 glycosylation 1252:1264 the O-linked glycosylation 1239:1264 the O-linked glycosylation of APP 1239:1271 Mutation of identified fingerprint residues in the SorLA CR-domains leads to changes in the O-linked glycosylation of APP when expressed in SH-SY5Y cells. 25525276 7 3 from changes 1228:1234 arg1 glycosylation 1252:1264 the O-linked glycosylation 1239:1264 the O-linked glycosylation of APP 1239:1271 Mutation of identified fingerprint residues in the SorLA CR-domains leads to changes in the O-linked glycosylation of APP when expressed in SH-SY5Y cells. 25525276 3 4 theme formation 493:501 arg1 determinants 459:470 the precise molecular determinants 437:470 the precise molecular determinants of SorLA·APP complex formation and the mechanisms responsible for the effect of binding on APP processing 437:576 The SorLA complement-type repeat (CR) domains associate in vitro with APP, but the precise molecular determinants of SorLA·APP complex formation and the mechanisms responsible for the effect of binding on APP processing have not yet been elucidated. 25525276 8 5 theme Alzheimer 1534:1542 arg1 disease 1544:1550 Alzheimer disease 1534:1550 Alzheimer disease 1534:1550 Our results provide novel information on the mechanisms behind the influence of SorLA activity on APP metabolism by controlling post-translational glycosylation in the Golgi, suggesting new strategies against amyloidogenesis in Alzheimer disease. 25525276 8 6 from amyloidogenesis 1515:1529 arg1 disease 1544:1550 Alzheimer disease 1534:1550 Alzheimer disease 1534:1550 Our results provide novel information on the mechanisms behind the influence of SorLA activity on APP metabolism by controlling post-translational glycosylation in the Golgi, suggesting new strategies against amyloidogenesis in Alzheimer disease. 25525276 7 7 theme SorLA 1202:1206 arg1 CR-domains 1208:1217 the SorLA CR-domains 1198:1217 the SorLA CR-domains 1198:1217 Mutation of identified fingerprint residues in the SorLA CR-domains leads to changes in the O-linked glycosylation of APP when expressed in SH-SY5Y cells. 25525276 7 8 from Mutation 1151:1158 arg1 CR-domains 1208:1217 the SorLA CR-domains 1198:1217 the SorLA CR-domains 1198:1217 Mutation of identified fingerprint residues in the SorLA CR-domains leads to changes in the O-linked glycosylation of APP when expressed in SH-SY5Y cells. 25525276 2 9 theme amyloid-β 339:347 arg1 peptide 349:355 the amyloid-β peptide 335:355 the amyloid-β peptide 335:355 SorLA interacts directly with the amyloid precursor protein (APP) and affects the processing of the precursor, leading to a decreased generation of the amyloid-β peptide. 25525276 2 10 theme precursor 287:295 arg1 processing 269:278 the processing 265:278 the processing of the precursor 265:295 SorLA interacts directly with the amyloid precursor protein (APP) and affects the processing of the precursor, leading to a decreased generation of the amyloid-β peptide. 25525276 4 11 theme SorLA 712:716 arg1 mutants 718:724 two SorLA mutants 708:724 two SorLA mutants harboring substitutions of the fingerprint residues in the central CR-domains 708:802 Here, we have generated protein expression constructs for SorLA devoid of the 11 CR-domains and for two SorLA mutants harboring substitutions of the fingerprint residues in the central CR-domains. 25525276 1 12 theme Alzheimer 168:176 arg1 disease 178:184 Alzheimer disease 168:184 Alzheimer disease 168:184 SorLA is a neuronal sorting receptor that is genetically associated with Alzheimer disease. 25525276 7 13 theme APP 1269:1271 arg1 glycosylation 1252:1264 the O-linked glycosylation 1239:1264 the O-linked glycosylation of APP 1239:1271 Mutation of identified fingerprint residues in the SorLA CR-domains leads to changes in the O-linked glycosylation of APP when expressed in SH-SY5Y cells. 25525276 5 14 theme Western 954:960 arg1 blotting/ELISAs 962:976 Western blotting/ELISAs 954:976 Western blotting/ELISAs 954:976 We generated SH-SY5Y cell lines that stably express these SorLA variants to study the binding and processing of APP using co-immunoprecipitation and Western blotting/ELISAs, respectively. 25525276 4 15 from substitutions 736:748 arg1 CR-domains 793:802 the central CR-domains 781:802 the central CR-domains 781:802 Here, we have generated protein expression constructs for SorLA devoid of the 11 CR-domains and for two SorLA mutants harboring substitutions of the fingerprint residues in the central CR-domains. 25525276 3 16 theme complex 485:491 arg1 formation 493:501 SorLA·APP complex formation 475:501 SorLA·APP complex formation 475:501 The SorLA complement-type repeat (CR) domains associate in vitro with APP, but the precise molecular determinants of SorLA·APP complex formation and the mechanisms responsible for the effect of binding on APP processing have not yet been elucidated. 25525276 4 17 theme CR-domains 689:698 arg1 devoid 672:677 devoid 672:677 devoid 672:677 Here, we have generated protein expression constructs for SorLA devoid of the 11 CR-domains and for two SorLA mutants harboring substitutions of the fingerprint residues in the central CR-domains. 25525276 4 18 theme devoid 672:677 arg1 SorLA 666:670 SorLA 666:670 SorLA devoid of the 11 CR-domains 666:698 Here, we have generated protein expression constructs for SorLA devoid of the 11 CR-domains and for two SorLA mutants harboring substitutions of the fingerprint residues in the central CR-domains. 25525276 7 19 theme identified 1163:1172 arg1 residues 1186:1193 identified fingerprint residues 1163:1193 identified fingerprint residues in the SorLA CR-domains 1163:1217 Mutation of identified fingerprint residues in the SorLA CR-domains leads to changes in the O-linked glycosylation of APP when expressed in SH-SY5Y cells. 25525276 5 20 theme SH-SY5Y 818:824 arg1 lines 831:835 SH-SY5Y cell lines 818:835 SH-SY5Y cell lines that stably express these SorLA variants to study the binding and processing of APP using co-immunoprecipitation and Western blotting/ELISAs, respectively 818:990 We generated SH-SY5Y cell lines that stably express these SorLA variants to study the binding and processing of APP using co-immunoprecipitation and Western blotting/ELISAs, respectively. 25525276 3 21 theme mechanisms 511:520 arg1 determinants 459:470 the precise molecular determinants 437:470 the precise molecular determinants of SorLA·APP complex formation and the mechanisms responsible for the effect of binding on APP processing 437:576 The SorLA complement-type repeat (CR) domains associate in vitro with APP, but the precise molecular determinants of SorLA·APP complex formation and the mechanisms responsible for the effect of binding on APP processing have not yet been elucidated. 25525276 4 22 theme protein 632:638 arg1 constructs 651:660 protein expression constructs 632:660 protein expression constructs for SorLA devoid of the 11 CR-domains and for two SorLA mutants harboring substitutions of the fingerprint residues in the central CR-domains 632:802 Here, we have generated protein expression constructs for SorLA devoid of the 11 CR-domains and for two SorLA mutants harboring substitutions of the fingerprint residues in the central CR-domains. 25525276 8 23 from information 1332:1342 arg1 mechanisms 1351:1360 the mechanisms 1347:1360 the mechanisms behind the influence of SorLA activity on APP metabolism 1347:1417 Our results provide novel information on the mechanisms behind the influence of SorLA activity on APP metabolism by controlling post-translational glycosylation in the Golgi, suggesting new strategies against amyloidogenesis in Alzheimer disease. 25525276 3 24 theme responsible 522:532 arg1 mechanisms 511:520 the mechanisms 507:520 the mechanisms responsible for the effect of binding on APP processing 507:576 The SorLA complement-type repeat (CR) domains associate in vitro with APP, but the precise molecular determinants of SorLA·APP complex formation and the mechanisms responsible for the effect of binding on APP processing have not yet been elucidated. 25525276 0 25 theme complement-type 6:20 arg1 domains 29:35 SorLA complement-type repeat domains 0:35 SorLA complement-type repeat domains 0:35 SorLA complement-type repeat domains protect the amyloid precursor protein against processing. 25525276 7 26 from residues 1186:1193 arg1 CR-domains 1208:1217 the SorLA CR-domains 1198:1217 the SorLA CR-domains 1198:1217 Mutation of identified fingerprint residues in the SorLA CR-domains leads to changes in the O-linked glycosylation of APP when expressed in SH-SY5Y cells. 25525276 8 27 from influence 1373:1381 arg1 metabolism 1408:1417 APP metabolism 1404:1417 APP metabolism 1404:1417 Our results provide novel information on the mechanisms behind the influence of SorLA activity on APP metabolism by controlling post-translational glycosylation in the Golgi, suggesting new strategies against amyloidogenesis in Alzheimer disease. 25525276 3 28 theme binding 552:558 arg1 effect 542:547 the effect 538:547 the effect of binding on APP processing 538:576 The SorLA complement-type repeat (CR) domains associate in vitro with APP, but the precise molecular determinants of SorLA·APP complex formation and the mechanisms responsible for the effect of binding on APP processing have not yet been elucidated. 25525276 7 29 theme fingerprint 1174:1184 arg1 residues 1186:1193 identified fingerprint residues 1163:1193 identified fingerprint residues in the SorLA CR-domains 1163:1217 Mutation of identified fingerprint residues in the SorLA CR-domains leads to changes in the O-linked glycosylation of APP when expressed in SH-SY5Y cells. 25525276 0 30 theme SorLA 0:4 arg1 domains 29:35 SorLA complement-type repeat domains 0:35 SorLA complement-type repeat domains 0:35 SorLA complement-type repeat domains protect the amyloid precursor protein against processing. 25525276 5 31 theme APP 917:919 arg1 binding 891:897 binding 891:897 binding 891:897 We generated SH-SY5Y cell lines that stably express these SorLA variants to study the binding and processing of APP using co-immunoprecipitation and Western blotting/ELISAs, respectively. 25525276 5 31 theme APP 917:919 arg1 processing 903:912 processing 903:912 processing 903:912 We generated SH-SY5Y cell lines that stably express these SorLA variants to study the binding and processing of APP using co-immunoprecipitation and Western blotting/ELISAs, respectively. 25525276 4 32 theme expression 640:649 arg1 constructs 651:660 protein expression constructs 632:660 protein expression constructs for SorLA devoid of the 11 CR-domains and for two SorLA mutants harboring substitutions of the fingerprint residues in the central CR-domains 632:802 Here, we have generated protein expression constructs for SorLA devoid of the 11 CR-domains and for two SorLA mutants harboring substitutions of the fingerprint residues in the central CR-domains. 25525276 3 33 theme SorLA 362:366 arg1 repeat 384:389 SorLA complement-type repeat 362:389 The SorLA complement-type repeat (CR) domains 358:402 The SorLA complement-type repeat (CR) domains associate in vitro with APP, but the precise molecular determinants of SorLA·APP complex formation and the mechanisms responsible for the effect of binding on APP processing have not yet been elucidated. 25525276 3 33 theme SorLA 362:366 arg1 CR 392:393 CR 392:393 CR 392:393 The SorLA complement-type repeat (CR) domains associate in vitro with APP, but the precise molecular determinants of SorLA·APP complex formation and the mechanisms responsible for the effect of binding on APP processing have not yet been elucidated. 25525276 8 34 theme APP 1404:1406 arg1 metabolism 1408:1417 APP metabolism 1404:1417 APP metabolism 1404:1417 Our results provide novel information on the mechanisms behind the influence of SorLA activity on APP metabolism by controlling post-translational glycosylation in the Golgi, suggesting new strategies against amyloidogenesis in Alzheimer disease. 25525276 8 35 theme SorLA 1386:1390 arg1 activity 1392:1399 SorLA activity 1386:1399 SorLA activity 1386:1399 Our results provide novel information on the mechanisms behind the influence of SorLA activity on APP metabolism by controlling post-translational glycosylation in the Golgi, suggesting new strategies against amyloidogenesis in Alzheimer disease. 25525276 0 36 theme repeat 22:27 arg1 domains 29:35 SorLA complement-type repeat domains 0:35 SorLA complement-type repeat domains 0:35 SorLA complement-type repeat domains protect the amyloid precursor protein against processing. 25525276 7 37 gly glycosylation 1252:1264 arg1 APP 1269:1271 APP 1269:1271 APP 1269:1271 Mutation of identified fingerprint residues in the SorLA CR-domains leads to changes in the O-linked glycosylation of APP when expressed in SH-SY5Y cells. 25525276 1 38 theme neuronal 106:113 arg1 receptor 123:130 a neuronal sorting receptor 104:130 a neuronal sorting receptor that is genetically associated with Alzheimer disease 104:184 SorLA is a neuronal sorting receptor that is genetically associated with Alzheimer disease. 25525276 1 38 theme neuronal 106:113 arg1 SorLA 95:99 SorLA 95:99 SorLA 95:99 SorLA is a neuronal sorting receptor that is genetically associated with Alzheimer disease. 25525276 3 39 theme precise 441:447 arg1 determinants 459:470 the precise molecular determinants 437:470 the precise molecular determinants of SorLA·APP complex formation and the mechanisms responsible for the effect of binding on APP processing 437:576 The SorLA complement-type repeat (CR) domains associate in vitro with APP, but the precise molecular determinants of SorLA·APP complex formation and the mechanisms responsible for the effect of binding on APP processing have not yet been elucidated. 25525276 7 40 theme SH-SY5Y 1291:1297 arg1 cells 1299:1303 SH-SY5Y cells 1291:1303 SH-SY5Y cells 1291:1303 Mutation of identified fingerprint residues in the SorLA CR-domains leads to changes in the O-linked glycosylation of APP when expressed in SH-SY5Y cells. 25525276 5 41 theme cell 826:829 arg1 lines 831:835 SH-SY5Y cell lines 818:835 SH-SY5Y cell lines that stably express these SorLA variants to study the binding and processing of APP using co-immunoprecipitation and Western blotting/ELISAs, respectively 818:990 We generated SH-SY5Y cell lines that stably express these SorLA variants to study the binding and processing of APP using co-immunoprecipitation and Western blotting/ELISAs, respectively. 25525276 8 42 dep mechanisms 1351:1360 arg1 behind 1362:1367 behind 1362:1367 behind the influence of SorLA activity on APP metabolism 1362:1417 Our results provide novel information on the mechanisms behind the influence of SorLA activity on APP metabolism by controlling post-translational glycosylation in the Golgi, suggesting new strategies against amyloidogenesis in Alzheimer disease. 25525276 4 43 theme central 785:791 arg1 CR-domains 793:802 the central CR-domains 781:802 the central CR-domains 781:802 Here, we have generated protein expression constructs for SorLA devoid of the 11 CR-domains and for two SorLA mutants harboring substitutions of the fingerprint residues in the central CR-domains. 25525276 7 44 theme O-linked 1243:1250 arg1 glycosylation 1252:1264 the O-linked glycosylation 1239:1264 the O-linked glycosylation of APP 1239:1271 Mutation of identified fingerprint residues in the SorLA CR-domains leads to changes in the O-linked glycosylation of APP when expressed in SH-SY5Y cells. 25525276 0 45 theme precursor 57:65 arg1 protein 67:73 the amyloid precursor protein 45:73 the amyloid precursor protein 45:73 SorLA complement-type repeat domains protect the amyloid precursor protein against processing. 25525276 7 46 from CR-domains 1208:1217 arg1 Mutation 1151:1158 Mutation 1151:1158 Mutation of identified fingerprint residues in the SorLA CR-domains 1151:1217 Mutation of identified fingerprint residues in the SorLA CR-domains leads to changes in the O-linked glycosylation of APP when expressed in SH-SY5Y cells. 25525276 3 47 theme APP 563:565 arg1 processing 567:576 APP processing 563:576 APP processing 563:576 The SorLA complement-type repeat (CR) domains associate in vitro with APP, but the precise molecular determinants of SorLA·APP complex formation and the mechanisms responsible for the effect of binding on APP processing have not yet been elucidated. 25525276 6 48 theme CR-cluster 1091:1100 arg1 deletion 1075:1082 deletion 1075:1082 deletion of the CR-cluster 1075:1100 We found that the SorLA CR-cluster is essential for interaction with APP and that deletion of the CR-cluster abolishes the protection against APP processing. 25525276 1 49 theme sorting 115:121 arg1 receptor 123:130 a neuronal sorting receptor 104:130 a neuronal sorting receptor that is genetically associated with Alzheimer disease 104:184 SorLA is a neuronal sorting receptor that is genetically associated with Alzheimer disease. 25525276 1 49 theme sorting 115:121 arg1 SorLA 95:99 SorLA 95:99 SorLA 95:99 SorLA is a neuronal sorting receptor that is genetically associated with Alzheimer disease. 25525276 0 50 theme amyloid 49:55 arg1 protein 67:73 the amyloid precursor protein 45:73 the amyloid precursor protein 45:73 SorLA complement-type repeat domains protect the amyloid precursor protein against processing. 25525276 8 51 theme new 1492:1494 arg1 strategies 1496:1505 new strategies 1492:1505 new strategies against amyloidogenesis in Alzheimer disease 1492:1550 Our results provide novel information on the mechanisms behind the influence of SorLA activity on APP metabolism by controlling post-translational glycosylation in the Golgi, suggesting new strategies against amyloidogenesis in Alzheimer disease. 25525276 2 52 theme amyloid 221:227 arg1 APP 248:250 APP 248:250 APP 248:250 SorLA interacts directly with the amyloid precursor protein (APP) and affects the processing of the precursor, leading to a decreased generation of the amyloid-β peptide. 25525276 2 52 theme amyloid 221:227 arg1 protein 239:245 amyloid precursor protein 221:245 the amyloid precursor protein (APP) 217:251 SorLA interacts directly with the amyloid precursor protein (APP) and affects the processing of the precursor, leading to a decreased generation of the amyloid-β peptide. 25525276 2 53 theme precursor 229:237 arg1 APP 248:250 APP 248:250 APP 248:250 SorLA interacts directly with the amyloid precursor protein (APP) and affects the processing of the precursor, leading to a decreased generation of the amyloid-β peptide. 25525276 2 53 theme precursor 229:237 arg1 protein 239:245 amyloid precursor protein 221:245 the amyloid precursor protein (APP) 217:251 SorLA interacts directly with the amyloid precursor protein (APP) and affects the processing of the precursor, leading to a decreased generation of the amyloid-β peptide. 25525276 4 54 from CR-domains 793:802 arg1 substitutions 736:748 substitutions 736:748 substitutions of the fingerprint residues in the central CR-domains 736:802 Here, we have generated protein expression constructs for SorLA devoid of the 11 CR-domains and for two SorLA mutants harboring substitutions of the fingerprint residues in the central CR-domains. 25525276 3 55 theme SorLA·APP 475:483 arg1 formation 493:501 SorLA·APP complex formation 475:501 SorLA·APP complex formation 475:501 The SorLA complement-type repeat (CR) domains associate in vitro with APP, but the precise molecular determinants of SorLA·APP complex formation and the mechanisms responsible for the effect of binding on APP processing have not yet been elucidated. 25525276 3 56 from effect 542:547 arg1 processing 567:576 APP processing 563:576 APP processing 563:576 The SorLA complement-type repeat (CR) domains associate in vitro with APP, but the precise molecular determinants of SorLA·APP complex formation and the mechanisms responsible for the effect of binding on APP processing have not yet been elucidated. 25525276 8 57 theme post-translational 1434:1451 arg1 glycosylation 1453:1465 post-translational glycosylation 1434:1465 post-translational glycosylation 1434:1465 Our results provide novel information on the mechanisms behind the influence of SorLA activity on APP metabolism by controlling post-translational glycosylation in the Golgi, suggesting new strategies against amyloidogenesis in Alzheimer disease. 25525276 4 58 theme residues 769:776 arg1 substitutions 736:748 substitutions 736:748 substitutions of the fingerprint residues in the central CR-domains 736:802 Here, we have generated protein expression constructs for SorLA devoid of the 11 CR-domains and for two SorLA mutants harboring substitutions of the fingerprint residues in the central CR-domains. 25525276 8 59 theme activity 1392:1399 arg1 influence 1373:1381 the influence 1369:1381 the influence of SorLA activity on APP metabolism 1369:1417 Our results provide novel information on the mechanisms behind the influence of SorLA activity on APP metabolism by controlling post-translational glycosylation in the Golgi, suggesting new strategies against amyloidogenesis in Alzheimer disease. 25525276 3 60 theme molecular 449:457 arg1 determinants 459:470 the precise molecular determinants 437:470 the precise molecular determinants of SorLA·APP complex formation and the mechanisms responsible for the effect of binding on APP processing 437:576 The SorLA complement-type repeat (CR) domains associate in vitro with APP, but the precise molecular determinants of SorLA·APP complex formation and the mechanisms responsible for the effect of binding on APP processing have not yet been elucidated. 25525276 5 61 dep binding 891:897 arg1 the 887:889 the 887:889 the 887:889 We generated SH-SY5Y cell lines that stably express these SorLA variants to study the binding and processing of APP using co-immunoprecipitation and Western blotting/ELISAs, respectively. 25525276 6 62 with interaction 1045:1055 arg1 APP 1062:1064 APP 1062:1064 APP 1062:1064 We found that the SorLA CR-cluster is essential for interaction with APP and that deletion of the CR-cluster abolishes the protection against APP processing. 25525276 4 63 theme fingerprint 757:767 arg1 residues 769:776 the fingerprint residues 753:776 the fingerprint residues in the central CR-domains 753:802 Here, we have generated protein expression constructs for SorLA devoid of the 11 CR-domains and for two SorLA mutants harboring substitutions of the fingerprint residues in the central CR-domains. 25525276 2 64 theme decreased 311:319 arg1 generation 321:330 a decreased generation 309:330 a decreased generation of the amyloid-β peptide 309:355 SorLA interacts directly with the amyloid precursor protein (APP) and affects the processing of the precursor, leading to a decreased generation of the amyloid-β peptide. 25525276 6 65 theme SorLA 1011:1015 arg1 essential 1031:1039 essential 1031:1039 essential 1031:1039 We found that the SorLA CR-cluster is essential for interaction with APP and that deletion of the CR-cluster abolishes the protection against APP processing. 25525276 6 65 theme SorLA 1011:1015 arg1 CR-cluster 1017:1026 the SorLA CR-cluster 1007:1026 the SorLA CR-cluster 1007:1026 We found that the SorLA CR-cluster is essential for interaction with APP and that deletion of the CR-cluster abolishes the protection against APP processing. 25525276 5 66 theme SorLA 863:867 arg1 variants 869:876 these SorLA variants 857:876 these SorLA variants 857:876 We generated SH-SY5Y cell lines that stably express these SorLA variants to study the binding and processing of APP using co-immunoprecipitation and Western blotting/ELISAs, respectively. 25525276 6 67 theme APP 1135:1137 arg1 processing 1139:1148 APP processing 1135:1148 APP processing 1135:1148 We found that the SorLA CR-cluster is essential for interaction with APP and that deletion of the CR-cluster abolishes the protection against APP processing. 25525276 3 68 theme complement-type 368:382 arg1 repeat 384:389 SorLA complement-type repeat 362:389 The SorLA complement-type repeat (CR) domains 358:402 The SorLA complement-type repeat (CR) domains associate in vitro with APP, but the precise molecular determinants of SorLA·APP complex formation and the mechanisms responsible for the effect of binding on APP processing have not yet been elucidated. 25525276 3 68 theme complement-type 368:382 arg1 CR 392:393 CR 392:393 CR 392:393 The SorLA complement-type repeat (CR) domains associate in vitro with APP, but the precise molecular determinants of SorLA·APP complex formation and the mechanisms responsible for the effect of binding on APP processing have not yet been elucidated. 25525276 4 69 from residues 769:776 arg1 CR-domains 793:802 the central CR-domains 781:802 the central CR-domains 781:802 Here, we have generated protein expression constructs for SorLA devoid of the 11 CR-domains and for two SorLA mutants harboring substitutions of the fingerprint residues in the central CR-domains. 25525276 3 70 theme repeat 384:389 arg1 domains 396:402 The SorLA complement-type repeat (CR) domains 358:402 The SorLA complement-type repeat (CR) domains 358:402 The SorLA complement-type repeat (CR) domains associate in vitro with APP, but the precise molecular determinants of SorLA·APP complex formation and the mechanisms responsible for the effect of binding on APP processing have not yet been elucidated. 25525276 7 71 theme residues 1186:1193 arg1 Mutation 1151:1158 Mutation 1151:1158 Mutation of identified fingerprint residues in the SorLA CR-domains 1151:1217 Mutation of identified fingerprint residues in the SorLA CR-domains leads to changes in the O-linked glycosylation of APP when expressed in SH-SY5Y cells. 26271046 6 0 theme mutants 1026:1032 arg1 series 1016:1021 a series 1014:1021 a series of mutants lacking potential N-glycosylation sites (N256, N370, N406, and N413) within GluA2 1014:1114 In the present study, using a series of mutants lacking potential N-glycosylation sites (N256, N370, N406, and N413) within GluA2, we demonstrated that the mutant lacking the N-glycan at N370 strongly suppressed the intracellular trafficking of GluA2 from the endoplasmic reticulum (ER) in HEK293 cells. 26271046 9 1 theme GluA2 1751:1755 arg1 expression 1737:1746 enhanced cell surface expression 1715:1746 enhanced cell surface expression of GluA2 1715:1755 Moreover, we found that N413 was the main potential site of the HNK-1 epitope that promoted the interaction of GluA2 with N-cadherin, resulting in enhanced cell surface expression of GluA2. 26271046 11 2 theme intracellular 1944:1956 arg1 trafficking 1958:1968 the intracellular trafficking 1940:1968 the intracellular trafficking 1940:1968 Thus, our data suggested that site-specific N-glycans on GluA2 regulate the intracellular trafficking and cell surface expression of AMPAR. 26271046 3 3 theme cell 693:696 arg1 expression 706:715 the cell surface expression 689:715 the cell surface expression of AMPAR 689:724 To date, a unique trisaccharide (HSO3-3GlcAβ1-3Galβ1-4GlcNAc), human natural killer-1 (HNK-1) carbohydrate, was found expressed specifically on N-linked glycans of GluA2 and regulated the cell surface expression of AMPAR and the spine maturation process. 26271046 7 4 theme AMPAR 1352:1356 arg1 subunit 1341:1347 a major subunit 1333:1347 a major subunit of AMPAR in neurons 1333:1367 Cell surface expression of GluA1, which is a major subunit of AMPAR in neurons, was also suppressed by co-expression of the GluA2 N370S mutant. 26271046 7 4 theme AMPAR 1352:1356 arg1 expression 1303:1312 Cell surface expression 1290:1312 Cell surface expression 1290:1312 Cell surface expression of GluA1, which is a major subunit of AMPAR in neurons, was also suppressed by co-expression of the GluA2 N370S mutant. 26271046 5 5 contain have 927:930 arg1 N-glycans 903:911 other N-glycans 897:911 other N-glycans on GluA2 897:920 Moreover, it is thought that other N-glycans on GluA2 also have potential roles in the regulation of AMPAR functions. 26271046 5 5 contain have 927:930 arg2 roles 942:946 potential roles 932:946 potential roles 932:946 Moreover, it is thought that other N-glycans on GluA2 also have potential roles in the regulation of AMPAR functions. 26271046 6 6 theme N-glycan 1161:1168 arg1 N370 1173:1176 the N-glycan at N370 1157:1176 the N-glycan at N370 1157:1176 In the present study, using a series of mutants lacking potential N-glycosylation sites (N256, N370, N406, and N413) within GluA2, we demonstrated that the mutant lacking the N-glycan at N370 strongly suppressed the intracellular trafficking of GluA2 from the endoplasmic reticulum (ER) in HEK293 cells. 26271046 10 7 from epitope 1768:1774 arg1 N-glycan 1779:1786 N-glycan 1779:1786 N-glycan 1779:1786 The HNK-1 epitope on N-glycan at the N413 of GluA2 was also involved in the cell surface expression of GluA1. 26271046 4 8 theme GluA2 817:821 arg1 N-glycans 804:812 N-glycans 804:812 N-glycans of GluA2 804:821 However, evidence that the HNK-1 epitope on N-glycans of GluA2 directly affects these phenomena is lacking. 26271046 3 9 theme AMPAR 720:724 arg1 expression 706:715 the cell surface expression 689:715 the cell surface expression of AMPAR 689:724 To date, a unique trisaccharide (HSO3-3GlcAβ1-3Galβ1-4GlcNAc), human natural killer-1 (HNK-1) carbohydrate, was found expressed specifically on N-linked glycans of GluA2 and regulated the cell surface expression of AMPAR and the spine maturation process. 26271046 3 9 theme AMPAR 720:724 arg1 process 751:757 the spine maturation process 730:757 the spine maturation process 730:757 To date, a unique trisaccharide (HSO3-3GlcAβ1-3Galβ1-4GlcNAc), human natural killer-1 (HNK-1) carbohydrate, was found expressed specifically on N-linked glycans of GluA2 and regulated the cell surface expression of AMPAR and the spine maturation process. 26271046 11 10 theme site-specific 1898:1910 arg1 N-glycans 1912:1920 site-specific N-glycans 1898:1920 site-specific N-glycans on GluA2 1898:1929 Thus, our data suggested that site-specific N-glycans on GluA2 regulate the intracellular trafficking and cell surface expression of AMPAR. 26271046 7 11 theme surface 1295:1301 arg1 expression 1303:1312 Cell surface expression 1290:1312 Cell surface expression 1290:1312 Cell surface expression of GluA1, which is a major subunit of AMPAR in neurons, was also suppressed by co-expression of the GluA2 N370S mutant. 26271046 7 11 theme surface 1295:1301 arg1 subunit 1341:1347 a major subunit 1333:1347 a major subunit of AMPAR in neurons 1333:1367 Cell surface expression of GluA1, which is a major subunit of AMPAR in neurons, was also suppressed by co-expression of the GluA2 N370S mutant. 26271046 11 12 theme surface 1979:1985 arg1 expression 1987:1996 cell surface expression 1974:1996 cell surface expression 1974:1996 Thus, our data suggested that site-specific N-glycans on GluA2 regulate the intracellular trafficking and cell surface expression of AMPAR. 26271046 6 13 theme endoplasmic 1246:1256 arg1 ER 1269:1270 ER 1269:1270 ER 1269:1270 In the present study, using a series of mutants lacking potential N-glycosylation sites (N256, N370, N406, and N413) within GluA2, we demonstrated that the mutant lacking the N-glycan at N370 strongly suppressed the intracellular trafficking of GluA2 from the endoplasmic reticulum (ER) in HEK293 cells. 26271046 6 13 theme endoplasmic 1246:1256 arg1 reticulum 1258:1266 the endoplasmic reticulum 1242:1266 the endoplasmic reticulum (ER) 1242:1271 In the present study, using a series of mutants lacking potential N-glycosylation sites (N256, N370, N406, and N413) within GluA2, we demonstrated that the mutant lacking the N-glycan at N370 strongly suppressed the intracellular trafficking of GluA2 from the endoplasmic reticulum (ER) in HEK293 cells. 26271046 10 14 theme surface 1839:1845 arg1 expression 1847:1856 the cell surface expression 1830:1856 the cell surface expression of GluA1 1830:1865 The HNK-1 epitope on N-glycan at the N413 of GluA2 was also involved in the cell surface expression of GluA1. 26271046 3 15 theme natural 574:580 arg1 trisaccharide 523:535 a unique trisaccharide 514:535 a unique trisaccharide (HSO3-3GlcAβ1-3Galβ1-4GlcNAc) 514:565 To date, a unique trisaccharide (HSO3-3GlcAβ1-3Galβ1-4GlcNAc), human natural killer-1 (HNK-1) carbohydrate, was found expressed specifically on N-linked glycans of GluA2 and regulated the cell surface expression of AMPAR and the spine maturation process. 26271046 3 15 theme natural 574:580 arg1 carbohydrate 599:610 human natural killer-1 (HNK-1) carbohydrate 568:610 human natural killer-1 (HNK-1) carbohydrate 568:610 To date, a unique trisaccharide (HSO3-3GlcAβ1-3Galβ1-4GlcNAc), human natural killer-1 (HNK-1) carbohydrate, was found expressed specifically on N-linked glycans of GluA2 and regulated the cell surface expression of AMPAR and the spine maturation process. 26271046 4 16 from epitope 793:799 arg1 N-glycans 804:812 N-glycans 804:812 N-glycans of GluA2 804:821 However, evidence that the HNK-1 epitope on N-glycans of GluA2 directly affects these phenomena is lacking. 26271046 9 17 theme main 1605:1608 arg1 site 1620:1623 the main potential site 1601:1623 the main potential site of the HNK-1 epitope that promoted the interaction of GluA2 with N-cadherin, resulting in enhanced cell surface expression of GluA2 1601:1755 Moreover, we found that N413 was the main potential site of the HNK-1 epitope that promoted the interaction of GluA2 with N-cadherin, resulting in enhanced cell surface expression of GluA2. 26271046 9 17 theme main 1605:1608 arg1 N413 1592:1595 N413 1592:1595 N413 1592:1595 Moreover, we found that N413 was the main potential site of the HNK-1 epitope that promoted the interaction of GluA2 with N-cadherin, resulting in enhanced cell surface expression of GluA2. 26271046 9 17 theme main 1605:1608 arg1 epitope 1638:1644 the HNK-1 epitope 1628:1644 the HNK-1 epitope that promoted the interaction of GluA2 with N-cadherin, resulting in enhanced cell surface expression of GluA2 1628:1755 Moreover, we found that N413 was the main potential site of the HNK-1 epitope that promoted the interaction of GluA2 with N-cadherin, resulting in enhanced cell surface expression of GluA2. 26271046 6 18 theme intracellular 1202:1214 arg1 trafficking 1216:1226 the intracellular trafficking 1198:1226 the intracellular trafficking of GluA2 from the endoplasmic reticulum (ER) 1198:1271 In the present study, using a series of mutants lacking potential N-glycosylation sites (N256, N370, N406, and N413) within GluA2, we demonstrated that the mutant lacking the N-glycan at N370 strongly suppressed the intracellular trafficking of GluA2 from the endoplasmic reticulum (ER) in HEK293 cells. 26271046 1 19 theme excitatory 296:305 arg1 transmissions 316:328 rapid excitatory synaptic transmissions 290:328 rapid excitatory synaptic transmissions 290:328 The AMPA-type glutamate receptor (AMPAR), which is a tetrameric complex composed of four subunits (GluA1-4) with several combinations, mediates the majority of rapid excitatory synaptic transmissions in the nervous system. 26271046 1 20 theme glutamate 144:152 arg1 AMPAR 164:168 AMPAR 164:168 AMPAR 164:168 The AMPA-type glutamate receptor (AMPAR), which is a tetrameric complex composed of four subunits (GluA1-4) with several combinations, mediates the majority of rapid excitatory synaptic transmissions in the nervous system. 26271046 1 20 theme glutamate 144:152 arg1 receptor 154:161 The AMPA-type glutamate receptor 130:161 The AMPA-type glutamate receptor (AMPAR) 130:169 The AMPA-type glutamate receptor (AMPAR), which is a tetrameric complex composed of four subunits (GluA1-4) with several combinations, mediates the majority of rapid excitatory synaptic transmissions in the nervous system. 26271046 1 20 theme glutamate 144:152 arg1 complex 194:200 a tetrameric complex 181:200 a tetrameric complex composed of four subunits (GluA1-4) with several combinations 181:262 The AMPA-type glutamate receptor (AMPAR), which is a tetrameric complex composed of four subunits (GluA1-4) with several combinations, mediates the majority of rapid excitatory synaptic transmissions in the nervous system. 26271046 2 21 theme bases 464:468 arg1 one 443:445 one 443:445 one 443:445 Cell surface expression levels of AMPAR modulate synaptic plasticity, which is considered one of the molecular bases for learning and memory formation. 26271046 2 21 theme bases 464:468 arg1 bases 464:468 the molecular bases 450:468 the molecular bases for learning and memory formation 450:502 Cell surface expression levels of AMPAR modulate synaptic plasticity, which is considered one of the molecular bases for learning and memory formation. 26271046 6 22 theme HEK293 1276:1281 arg1 cells 1283:1287 HEK293 cells 1276:1287 HEK293 cells 1276:1287 In the present study, using a series of mutants lacking potential N-glycosylation sites (N256, N370, N406, and N413) within GluA2, we demonstrated that the mutant lacking the N-glycan at N370 strongly suppressed the intracellular trafficking of GluA2 from the endoplasmic reticulum (ER) in HEK293 cells. 26271046 1 23 theme transmissions 316:328 arg1 majority 278:285 the majority 274:285 the majority of rapid excitatory synaptic transmissions 274:328 The AMPA-type glutamate receptor (AMPAR), which is a tetrameric complex composed of four subunits (GluA1-4) with several combinations, mediates the majority of rapid excitatory synaptic transmissions in the nervous system. 26271046 9 24 theme epitope 1638:1644 arg1 site 1620:1623 the main potential site 1601:1623 the main potential site of the HNK-1 epitope that promoted the interaction of GluA2 with N-cadherin, resulting in enhanced cell surface expression of GluA2 1601:1755 Moreover, we found that N413 was the main potential site of the HNK-1 epitope that promoted the interaction of GluA2 with N-cadherin, resulting in enhanced cell surface expression of GluA2. 26271046 9 24 theme epitope 1638:1644 arg1 N413 1592:1595 N413 1592:1595 N413 1592:1595 Moreover, we found that N413 was the main potential site of the HNK-1 epitope that promoted the interaction of GluA2 with N-cadherin, resulting in enhanced cell surface expression of GluA2. 26271046 9 24 theme epitope 1638:1644 arg1 epitope 1638:1644 the HNK-1 epitope 1628:1644 the HNK-1 epitope that promoted the interaction of GluA2 with N-cadherin, resulting in enhanced cell surface expression of GluA2 1628:1755 Moreover, we found that N413 was the main potential site of the HNK-1 epitope that promoted the interaction of GluA2 with N-cadherin, resulting in enhanced cell surface expression of GluA2. 26271046 0 25 theme Surface 77:83 arg1 Expression 85:94 Cell Surface Expression 72:94 Cell Surface Expression of AMPA-Type Glutamate Receptors 72:127 Role of Site-Specific N-Glycans Expressed on GluA2 in the Regulation of Cell Surface Expression of AMPA-Type Glutamate Receptors. 26271046 5 26 theme potential 932:940 arg1 roles 942:946 potential roles 932:946 potential roles 932:946 Moreover, it is thought that other N-glycans on GluA2 also have potential roles in the regulation of AMPAR functions. 26271046 6 27 gly N-glycosylation 1052:1066 arg2 N256 1075:1078 N256 1075:1078 N256 1075:1078 In the present study, using a series of mutants lacking potential N-glycosylation sites (N256, N370, N406, and N413) within GluA2, we demonstrated that the mutant lacking the N-glycan at N370 strongly suppressed the intracellular trafficking of GluA2 from the endoplasmic reticulum (ER) in HEK293 cells. 26271046 6 27 gly N-glycosylation 1052:1066 arg2 sites 1068:1072 potential N-glycosylation sites 1042:1072 potential N-glycosylation sites (N256, N370, N406, and N413) within GluA2 1042:1114 In the present study, using a series of mutants lacking potential N-glycosylation sites (N256, N370, N406, and N413) within GluA2, we demonstrated that the mutant lacking the N-glycan at N370 strongly suppressed the intracellular trafficking of GluA2 from the endoplasmic reticulum (ER) in HEK293 cells. 26271046 6 27 gly N-glycosylation 1052:1066 arg2 N413 1097:1100 N413 1097:1100 N413 1097:1100 In the present study, using a series of mutants lacking potential N-glycosylation sites (N256, N370, N406, and N413) within GluA2, we demonstrated that the mutant lacking the N-glycan at N370 strongly suppressed the intracellular trafficking of GluA2 from the endoplasmic reticulum (ER) in HEK293 cells. 26271046 6 27 gly N-glycosylation 1052:1066 arg2 N406 1087:1090 N406 1087:1090 N406 1087:1090 In the present study, using a series of mutants lacking potential N-glycosylation sites (N256, N370, N406, and N413) within GluA2, we demonstrated that the mutant lacking the N-glycan at N370 strongly suppressed the intracellular trafficking of GluA2 from the endoplasmic reticulum (ER) in HEK293 cells. 26271046 6 27 gly N-glycosylation 1052:1066 arg2 N370 1081:1084 N370 1081:1084 N370 1081:1084 In the present study, using a series of mutants lacking potential N-glycosylation sites (N256, N370, N406, and N413) within GluA2, we demonstrated that the mutant lacking the N-glycan at N370 strongly suppressed the intracellular trafficking of GluA2 from the endoplasmic reticulum (ER) in HEK293 cells. 26271046 2 28 theme surface 358:364 arg1 levels 377:382 Cell surface expression levels 353:382 Cell surface expression levels of AMPAR 353:391 Cell surface expression levels of AMPAR modulate synaptic plasticity, which is considered one of the molecular bases for learning and memory formation. 26271046 1 29 theme several 243:249 arg1 combinations 251:262 several combinations 243:262 several combinations 243:262 The AMPA-type glutamate receptor (AMPAR), which is a tetrameric complex composed of four subunits (GluA1-4) with several combinations, mediates the majority of rapid excitatory synaptic transmissions in the nervous system. 26271046 5 30 theme other 897:901 arg1 N-glycans 903:911 other N-glycans 897:911 other N-glycans on GluA2 897:920 Moreover, it is thought that other N-glycans on GluA2 also have potential roles in the regulation of AMPAR functions. 26271046 9 31 theme GluA2 1679:1683 arg1 interaction 1664:1674 the interaction 1660:1674 the interaction of GluA2 with N-cadherin 1660:1699 Moreover, we found that N413 was the main potential site of the HNK-1 epitope that promoted the interaction of GluA2 with N-cadherin, resulting in enhanced cell surface expression of GluA2. 26271046 2 32 theme synaptic 402:409 arg1 plasticity 411:420 synaptic plasticity 402:420 synaptic plasticity 402:420 Cell surface expression levels of AMPAR modulate synaptic plasticity, which is considered one of the molecular bases for learning and memory formation. 26271046 0 33 theme Site-Specific 8:20 arg1 N-Glycans 22:30 Site-Specific N-Glycans 8:30 Site-Specific N-Glycans 8:30 Role of Site-Specific N-Glycans Expressed on GluA2 in the Regulation of Cell Surface Expression of AMPA-Type Glutamate Receptors. 26271046 6 34 from reticulum 1258:1266 arg1 trafficking 1216:1226 the intracellular trafficking 1198:1226 the intracellular trafficking of GluA2 from the endoplasmic reticulum (ER) 1198:1271 In the present study, using a series of mutants lacking potential N-glycosylation sites (N256, N370, N406, and N413) within GluA2, we demonstrated that the mutant lacking the N-glycan at N370 strongly suppressed the intracellular trafficking of GluA2 from the endoplasmic reticulum (ER) in HEK293 cells. 26271046 7 35 theme GluA2 1414:1418 arg1 mutant 1426:1431 the GluA2 N370S mutant 1410:1431 the GluA2 N370S mutant 1410:1431 Cell surface expression of GluA1, which is a major subunit of AMPAR in neurons, was also suppressed by co-expression of the GluA2 N370S mutant. 26271046 6 36 theme present 993:999 arg1 study 1001:1005 the present study 989:1005 the present study 989:1005 In the present study, using a series of mutants lacking potential N-glycosylation sites (N256, N370, N406, and N413) within GluA2, we demonstrated that the mutant lacking the N-glycan at N370 strongly suppressed the intracellular trafficking of GluA2 from the endoplasmic reticulum (ER) in HEK293 cells. 26271046 2 37 theme AMPAR 387:391 arg1 levels 377:382 Cell surface expression levels 353:382 Cell surface expression levels of AMPAR 353:391 Cell surface expression levels of AMPAR modulate synaptic plasticity, which is considered one of the molecular bases for learning and memory formation. 26271046 5 38 theme AMPAR 969:973 arg1 functions 975:983 AMPAR functions 969:983 AMPAR functions 969:983 Moreover, it is thought that other N-glycans on GluA2 also have potential roles in the regulation of AMPAR functions. 26271046 9 39 theme enhanced 1715:1722 arg1 expression 1737:1746 enhanced cell surface expression 1715:1746 enhanced cell surface expression of GluA2 1715:1755 Moreover, we found that N413 was the main potential site of the HNK-1 epitope that promoted the interaction of GluA2 with N-cadherin, resulting in enhanced cell surface expression of GluA2. 26271046 3 40 theme N-linked 649:656 arg1 glycans 658:664 N-linked glycans 649:664 N-linked glycans of GluA2 649:673 To date, a unique trisaccharide (HSO3-3GlcAβ1-3Galβ1-4GlcNAc), human natural killer-1 (HNK-1) carbohydrate, was found expressed specifically on N-linked glycans of GluA2 and regulated the cell surface expression of AMPAR and the spine maturation process. 26271046 6 41 dep sites 1068:1072 arg1 sites 1068:1072 potential N-glycosylation sites 1042:1072 potential N-glycosylation sites (N256, N370, N406, and N413) within GluA2 1042:1114 In the present study, using a series of mutants lacking potential N-glycosylation sites (N256, N370, N406, and N413) within GluA2, we demonstrated that the mutant lacking the N-glycan at N370 strongly suppressed the intracellular trafficking of GluA2 from the endoplasmic reticulum (ER) in HEK293 cells. 26271046 6 41 dep sites 1068:1072 arg1 N406 1087:1090 N406 1087:1090 N406 1087:1090 In the present study, using a series of mutants lacking potential N-glycosylation sites (N256, N370, N406, and N413) within GluA2, we demonstrated that the mutant lacking the N-glycan at N370 strongly suppressed the intracellular trafficking of GluA2 from the endoplasmic reticulum (ER) in HEK293 cells. 26271046 6 41 dep sites 1068:1072 arg1 N413 1097:1100 N413 1097:1100 N413 1097:1100 In the present study, using a series of mutants lacking potential N-glycosylation sites (N256, N370, N406, and N413) within GluA2, we demonstrated that the mutant lacking the N-glycan at N370 strongly suppressed the intracellular trafficking of GluA2 from the endoplasmic reticulum (ER) in HEK293 cells. 26271046 6 41 dep sites 1068:1072 arg1 N370 1081:1084 N370 1081:1084 N370 1081:1084 In the present study, using a series of mutants lacking potential N-glycosylation sites (N256, N370, N406, and N413) within GluA2, we demonstrated that the mutant lacking the N-glycan at N370 strongly suppressed the intracellular trafficking of GluA2 from the endoplasmic reticulum (ER) in HEK293 cells. 26271046 6 41 dep sites 1068:1072 arg1 N256 1075:1078 N256 1075:1078 N256 1075:1078 In the present study, using a series of mutants lacking potential N-glycosylation sites (N256, N370, N406, and N413) within GluA2, we demonstrated that the mutant lacking the N-glycan at N370 strongly suppressed the intracellular trafficking of GluA2 from the endoplasmic reticulum (ER) in HEK293 cells. 26271046 6 42 theme N-glycosylation 1052:1066 arg1 sites 1068:1072 potential N-glycosylation sites 1042:1072 potential N-glycosylation sites (N256, N370, N406, and N413) within GluA2 1042:1114 In the present study, using a series of mutants lacking potential N-glycosylation sites (N256, N370, N406, and N413) within GluA2, we demonstrated that the mutant lacking the N-glycan at N370 strongly suppressed the intracellular trafficking of GluA2 from the endoplasmic reticulum (ER) in HEK293 cells. 26271046 6 42 theme N-glycosylation 1052:1066 arg1 N406 1087:1090 N406 1087:1090 N406 1087:1090 In the present study, using a series of mutants lacking potential N-glycosylation sites (N256, N370, N406, and N413) within GluA2, we demonstrated that the mutant lacking the N-glycan at N370 strongly suppressed the intracellular trafficking of GluA2 from the endoplasmic reticulum (ER) in HEK293 cells. 26271046 6 42 theme N-glycosylation 1052:1066 arg1 N413 1097:1100 N413 1097:1100 N413 1097:1100 In the present study, using a series of mutants lacking potential N-glycosylation sites (N256, N370, N406, and N413) within GluA2, we demonstrated that the mutant lacking the N-glycan at N370 strongly suppressed the intracellular trafficking of GluA2 from the endoplasmic reticulum (ER) in HEK293 cells. 26271046 6 42 theme N-glycosylation 1052:1066 arg1 N370 1081:1084 N370 1081:1084 N370 1081:1084 In the present study, using a series of mutants lacking potential N-glycosylation sites (N256, N370, N406, and N413) within GluA2, we demonstrated that the mutant lacking the N-glycan at N370 strongly suppressed the intracellular trafficking of GluA2 from the endoplasmic reticulum (ER) in HEK293 cells. 26271046 6 42 theme N-glycosylation 1052:1066 arg1 N256 1075:1078 N256 1075:1078 N256 1075:1078 In the present study, using a series of mutants lacking potential N-glycosylation sites (N256, N370, N406, and N413) within GluA2, we demonstrated that the mutant lacking the N-glycan at N370 strongly suppressed the intracellular trafficking of GluA2 from the endoplasmic reticulum (ER) in HEK293 cells. 26271046 9 43 theme surface 1729:1735 arg1 expression 1737:1746 enhanced cell surface expression 1715:1746 enhanced cell surface expression of GluA2 1715:1755 Moreover, we found that N413 was the main potential site of the HNK-1 epitope that promoted the interaction of GluA2 with N-cadherin, resulting in enhanced cell surface expression of GluA2. 26271046 11 44 theme cell 1974:1977 arg1 expression 1987:1996 cell surface expression 1974:1996 cell surface expression 1974:1996 Thus, our data suggested that site-specific N-glycans on GluA2 regulate the intracellular trafficking and cell surface expression of AMPAR. 26271046 10 45 theme HNK-1 1762:1766 arg1 epitope 1768:1774 The HNK-1 epitope 1758:1774 The HNK-1 epitope on N-glycan at the N413 of GluA2 1758:1807 The HNK-1 epitope on N-glycan at the N413 of GluA2 was also involved in the cell surface expression of GluA1. 26271046 3 46 theme surface 698:704 arg1 expression 706:715 the cell surface expression 689:715 the cell surface expression of AMPAR 689:724 To date, a unique trisaccharide (HSO3-3GlcAβ1-3Galβ1-4GlcNAc), human natural killer-1 (HNK-1) carbohydrate, was found expressed specifically on N-linked glycans of GluA2 and regulated the cell surface expression of AMPAR and the spine maturation process. 26271046 6 47 theme at 1170:1171 arg1 N370 1173:1176 the N-glycan at N370 1157:1176 the N-glycan at N370 1157:1176 In the present study, using a series of mutants lacking potential N-glycosylation sites (N256, N370, N406, and N413) within GluA2, we demonstrated that the mutant lacking the N-glycan at N370 strongly suppressed the intracellular trafficking of GluA2 from the endoplasmic reticulum (ER) in HEK293 cells. 26271046 4 48 dep evidence 769:776 arg1 affects 832:838 affects 832:838 affects these phenomena 832:854 However, evidence that the HNK-1 epitope on N-glycans of GluA2 directly affects these phenomena is lacking. 26271046 7 49 theme major 1335:1339 arg1 subunit 1341:1347 a major subunit 1333:1347 a major subunit of AMPAR in neurons 1333:1367 Cell surface expression of GluA1, which is a major subunit of AMPAR in neurons, was also suppressed by co-expression of the GluA2 N370S mutant. 26271046 7 49 theme major 1335:1339 arg1 expression 1303:1312 Cell surface expression 1290:1312 Cell surface expression 1290:1312 Cell surface expression of GluA1, which is a major subunit of AMPAR in neurons, was also suppressed by co-expression of the GluA2 N370S mutant. 26271046 11 50 theme AMPAR 2001:2005 arg1 expression 1987:1996 cell surface expression 1974:1996 cell surface expression 1974:1996 Thus, our data suggested that site-specific N-glycans on GluA2 regulate the intracellular trafficking and cell surface expression of AMPAR. 26271046 11 50 theme AMPAR 2001:2005 arg1 trafficking 1958:1968 the intracellular trafficking 1940:1968 the intracellular trafficking 1940:1968 Thus, our data suggested that site-specific N-glycans on GluA2 regulate the intracellular trafficking and cell surface expression of AMPAR. 26271046 9 51 theme HNK-1 1632:1636 arg1 epitope 1638:1644 the HNK-1 epitope 1628:1644 the HNK-1 epitope that promoted the interaction of GluA2 with N-cadherin, resulting in enhanced cell surface expression of GluA2 1628:1755 Moreover, we found that N413 was the main potential site of the HNK-1 epitope that promoted the interaction of GluA2 with N-cadherin, resulting in enhanced cell surface expression of GluA2. 26271046 7 52 from subunit 1341:1347 arg1 neurons 1361:1367 neurons 1361:1367 neurons 1361:1367 Cell surface expression of GluA1, which is a major subunit of AMPAR in neurons, was also suppressed by co-expression of the GluA2 N370S mutant. 26271046 7 53 theme GluA1 1317:1321 arg1 expression 1303:1312 Cell surface expression 1290:1312 Cell surface expression 1290:1312 Cell surface expression of GluA1, which is a major subunit of AMPAR in neurons, was also suppressed by co-expression of the GluA2 N370S mutant. 26271046 7 53 theme GluA1 1317:1321 arg1 subunit 1341:1347 a major subunit 1333:1347 a major subunit of AMPAR in neurons 1333:1367 Cell surface expression of GluA1, which is a major subunit of AMPAR in neurons, was also suppressed by co-expression of the GluA2 N370S mutant. 26271046 0 54 theme Receptors 119:127 arg1 Expression 85:94 Cell Surface Expression 72:94 Cell Surface Expression of AMPA-Type Glutamate Receptors 72:127 Role of Site-Specific N-Glycans Expressed on GluA2 in the Regulation of Cell Surface Expression of AMPA-Type Glutamate Receptors. 26271046 9 55 with interaction 1664:1674 arg1 N-cadherin 1690:1699 N-cadherin 1690:1699 N-cadherin 1690:1699 Moreover, we found that N413 was the main potential site of the HNK-1 epitope that promoted the interaction of GluA2 with N-cadherin, resulting in enhanced cell surface expression of GluA2. 26271046 10 56 theme GluA2 1803:1807 arg1 N413 1795:1798 the N413 1791:1798 the N413 of GluA2 1791:1807 The HNK-1 epitope on N-glycan at the N413 of GluA2 was also involved in the cell surface expression of GluA1. 26271046 3 57 theme human 568:572 arg1 trisaccharide 523:535 a unique trisaccharide 514:535 a unique trisaccharide (HSO3-3GlcAβ1-3Galβ1-4GlcNAc) 514:565 To date, a unique trisaccharide (HSO3-3GlcAβ1-3Galβ1-4GlcNAc), human natural killer-1 (HNK-1) carbohydrate, was found expressed specifically on N-linked glycans of GluA2 and regulated the cell surface expression of AMPAR and the spine maturation process. 26271046 3 57 theme human 568:572 arg1 carbohydrate 599:610 human natural killer-1 (HNK-1) carbohydrate 568:610 human natural killer-1 (HNK-1) carbohydrate 568:610 To date, a unique trisaccharide (HSO3-3GlcAβ1-3Galβ1-4GlcNAc), human natural killer-1 (HNK-1) carbohydrate, was found expressed specifically on N-linked glycans of GluA2 and regulated the cell surface expression of AMPAR and the spine maturation process. 26271046 1 58 theme tetrameric 183:192 arg1 receptor 154:161 The AMPA-type glutamate receptor 130:161 The AMPA-type glutamate receptor (AMPAR) 130:169 The AMPA-type glutamate receptor (AMPAR), which is a tetrameric complex composed of four subunits (GluA1-4) with several combinations, mediates the majority of rapid excitatory synaptic transmissions in the nervous system. 26271046 1 58 theme tetrameric 183:192 arg1 complex 194:200 a tetrameric complex 181:200 a tetrameric complex composed of four subunits (GluA1-4) with several combinations 181:262 The AMPA-type glutamate receptor (AMPAR), which is a tetrameric complex composed of four subunits (GluA1-4) with several combinations, mediates the majority of rapid excitatory synaptic transmissions in the nervous system. 26271046 7 59 theme Cell 1290:1293 arg1 expression 1303:1312 Cell surface expression 1290:1312 Cell surface expression 1290:1312 Cell surface expression of GluA1, which is a major subunit of AMPAR in neurons, was also suppressed by co-expression of the GluA2 N370S mutant. 26271046 7 59 theme Cell 1290:1293 arg1 subunit 1341:1347 a major subunit 1333:1347 a major subunit of AMPAR in neurons 1333:1367 Cell surface expression of GluA1, which is a major subunit of AMPAR in neurons, was also suppressed by co-expression of the GluA2 N370S mutant. 26271046 10 60 theme cell 1834:1837 arg1 expression 1847:1856 the cell surface expression 1830:1856 the cell surface expression of GluA1 1830:1865 The HNK-1 epitope on N-glycan at the N413 of GluA2 was also involved in the cell surface expression of GluA1. 26271046 6 61 theme GluA2 1231:1235 arg1 trafficking 1216:1226 the intracellular trafficking 1198:1226 the intracellular trafficking of GluA2 from the endoplasmic reticulum (ER) 1198:1271 In the present study, using a series of mutants lacking potential N-glycosylation sites (N256, N370, N406, and N413) within GluA2, we demonstrated that the mutant lacking the N-glycan at N370 strongly suppressed the intracellular trafficking of GluA2 from the endoplasmic reticulum (ER) in HEK293 cells. 26271046 8 62 dep mutant 1444:1449 arg1 The 1434:1436 The 1434:1436 The 1434:1436 The N370S mutant and wild-type GluA2 were co-immunoprecipitated with GluA1, suggesting that N370S was properly associated with GluA1. 26271046 8 62 dep mutant 1444:1449 arg1 GluA2 1465:1469 GluA2 1465:1469 GluA2 1465:1469 The N370S mutant and wild-type GluA2 were co-immunoprecipitated with GluA1, suggesting that N370S was properly associated with GluA1. 26271046 10 63 from N413 1795:1798 arg1 epitope 1768:1774 The HNK-1 epitope 1758:1774 The HNK-1 epitope on N-glycan at the N413 of GluA2 1758:1807 The HNK-1 epitope on N-glycan at the N413 of GluA2 was also involved in the cell surface expression of GluA1. 26271046 3 64 theme spine 734:738 arg1 process 751:757 the spine maturation process 730:757 the spine maturation process 730:757 To date, a unique trisaccharide (HSO3-3GlcAβ1-3Galβ1-4GlcNAc), human natural killer-1 (HNK-1) carbohydrate, was found expressed specifically on N-linked glycans of GluA2 and regulated the cell surface expression of AMPAR and the spine maturation process. 26271046 3 65 theme HNK-1 592:596 arg1 trisaccharide 523:535 a unique trisaccharide 514:535 a unique trisaccharide (HSO3-3GlcAβ1-3Galβ1-4GlcNAc) 514:565 To date, a unique trisaccharide (HSO3-3GlcAβ1-3Galβ1-4GlcNAc), human natural killer-1 (HNK-1) carbohydrate, was found expressed specifically on N-linked glycans of GluA2 and regulated the cell surface expression of AMPAR and the spine maturation process. 26271046 3 65 theme HNK-1 592:596 arg1 carbohydrate 599:610 human natural killer-1 (HNK-1) carbohydrate 568:610 human natural killer-1 (HNK-1) carbohydrate 568:610 To date, a unique trisaccharide (HSO3-3GlcAβ1-3Galβ1-4GlcNAc), human natural killer-1 (HNK-1) carbohydrate, was found expressed specifically on N-linked glycans of GluA2 and regulated the cell surface expression of AMPAR and the spine maturation process. 26271046 3 66 theme unique 516:521 arg1 trisaccharide 523:535 a unique trisaccharide 514:535 a unique trisaccharide (HSO3-3GlcAβ1-3Galβ1-4GlcNAc) 514:565 To date, a unique trisaccharide (HSO3-3GlcAβ1-3Galβ1-4GlcNAc), human natural killer-1 (HNK-1) carbohydrate, was found expressed specifically on N-linked glycans of GluA2 and regulated the cell surface expression of AMPAR and the spine maturation process. 26271046 3 66 theme unique 516:521 arg1 carbohydrate 599:610 human natural killer-1 (HNK-1) carbohydrate 568:610 human natural killer-1 (HNK-1) carbohydrate 568:610 To date, a unique trisaccharide (HSO3-3GlcAβ1-3Galβ1-4GlcNAc), human natural killer-1 (HNK-1) carbohydrate, was found expressed specifically on N-linked glycans of GluA2 and regulated the cell surface expression of AMPAR and the spine maturation process. 26271046 3 66 theme unique 516:521 arg1 HSO3-3GlcAβ1-3Galβ1-4GlcNAc 538:564 HSO3-3GlcAβ1-3Galβ1-4GlcNAc 538:564 HSO3-3GlcAβ1-3Galβ1-4GlcNAc 538:564 To date, a unique trisaccharide (HSO3-3GlcAβ1-3Galβ1-4GlcNAc), human natural killer-1 (HNK-1) carbohydrate, was found expressed specifically on N-linked glycans of GluA2 and regulated the cell surface expression of AMPAR and the spine maturation process. 26271046 9 67 theme potential 1610:1618 arg1 site 1620:1623 the main potential site 1601:1623 the main potential site of the HNK-1 epitope that promoted the interaction of GluA2 with N-cadherin, resulting in enhanced cell surface expression of GluA2 1601:1755 Moreover, we found that N413 was the main potential site of the HNK-1 epitope that promoted the interaction of GluA2 with N-cadherin, resulting in enhanced cell surface expression of GluA2. 26271046 9 67 theme potential 1610:1618 arg1 N413 1592:1595 N413 1592:1595 N413 1592:1595 Moreover, we found that N413 was the main potential site of the HNK-1 epitope that promoted the interaction of GluA2 with N-cadherin, resulting in enhanced cell surface expression of GluA2. 26271046 9 67 theme potential 1610:1618 arg1 epitope 1638:1644 the HNK-1 epitope 1628:1644 the HNK-1 epitope that promoted the interaction of GluA2 with N-cadherin, resulting in enhanced cell surface expression of GluA2 1628:1755 Moreover, we found that N413 was the main potential site of the HNK-1 epitope that promoted the interaction of GluA2 with N-cadherin, resulting in enhanced cell surface expression of GluA2. 26271046 10 68 theme GluA1 1861:1865 arg1 expression 1847:1856 the cell surface expression 1830:1856 the cell surface expression of GluA1 1830:1865 The HNK-1 epitope on N-glycan at the N413 of GluA2 was also involved in the cell surface expression of GluA1. 26271046 3 69 theme killer-1 582:589 arg1 trisaccharide 523:535 a unique trisaccharide 514:535 a unique trisaccharide (HSO3-3GlcAβ1-3Galβ1-4GlcNAc) 514:565 To date, a unique trisaccharide (HSO3-3GlcAβ1-3Galβ1-4GlcNAc), human natural killer-1 (HNK-1) carbohydrate, was found expressed specifically on N-linked glycans of GluA2 and regulated the cell surface expression of AMPAR and the spine maturation process. 26271046 3 69 theme killer-1 582:589 arg1 carbohydrate 599:610 human natural killer-1 (HNK-1) carbohydrate 568:610 human natural killer-1 (HNK-1) carbohydrate 568:610 To date, a unique trisaccharide (HSO3-3GlcAβ1-3Galβ1-4GlcNAc), human natural killer-1 (HNK-1) carbohydrate, was found expressed specifically on N-linked glycans of GluA2 and regulated the cell surface expression of AMPAR and the spine maturation process. 26271046 1 70 theme AMPA-type 134:142 arg1 AMPAR 164:168 AMPAR 164:168 AMPAR 164:168 The AMPA-type glutamate receptor (AMPAR), which is a tetrameric complex composed of four subunits (GluA1-4) with several combinations, mediates the majority of rapid excitatory synaptic transmissions in the nervous system. 26271046 1 70 theme AMPA-type 134:142 arg1 receptor 154:161 The AMPA-type glutamate receptor 130:161 The AMPA-type glutamate receptor (AMPAR) 130:169 The AMPA-type glutamate receptor (AMPAR), which is a tetrameric complex composed of four subunits (GluA1-4) with several combinations, mediates the majority of rapid excitatory synaptic transmissions in the nervous system. 26271046 1 70 theme AMPA-type 134:142 arg1 complex 194:200 a tetrameric complex 181:200 a tetrameric complex composed of four subunits (GluA1-4) with several combinations 181:262 The AMPA-type glutamate receptor (AMPAR), which is a tetrameric complex composed of four subunits (GluA1-4) with several combinations, mediates the majority of rapid excitatory synaptic transmissions in the nervous system. 26271046 0 71 theme Cell 72:75 arg1 Expression 85:94 Cell Surface Expression 72:94 Cell Surface Expression of AMPA-Type Glutamate Receptors 72:127 Role of Site-Specific N-Glycans Expressed on GluA2 in the Regulation of Cell Surface Expression of AMPA-Type Glutamate Receptors. 26271046 1 72 theme synaptic 307:314 arg1 transmissions 316:328 rapid excitatory synaptic transmissions 290:328 rapid excitatory synaptic transmissions 290:328 The AMPA-type glutamate receptor (AMPAR), which is a tetrameric complex composed of four subunits (GluA1-4) with several combinations, mediates the majority of rapid excitatory synaptic transmissions in the nervous system. 26271046 2 73 theme molecular 454:462 arg1 bases 464:468 the molecular bases 450:468 the molecular bases for learning and memory formation 450:502 Cell surface expression levels of AMPAR modulate synaptic plasticity, which is considered one of the molecular bases for learning and memory formation. 26271046 0 74 theme Expression 85:94 arg1 Regulation 58:67 the Regulation 54:67 the Regulation of Cell Surface Expression of AMPA-Type Glutamate Receptors 54:127 Role of Site-Specific N-Glycans Expressed on GluA2 in the Regulation of Cell Surface Expression of AMPA-Type Glutamate Receptors. 26271046 7 75 theme mutant 1426:1431 arg1 co-expression 1393:1405 co-expression 1393:1405 co-expression of the GluA2 N370S mutant 1393:1431 Cell surface expression of GluA1, which is a major subunit of AMPAR in neurons, was also suppressed by co-expression of the GluA2 N370S mutant. 26271046 11 76 from N-glycans 1912:1920 arg1 GluA2 1925:1929 GluA2 1925:1929 GluA2 1925:1929 Thus, our data suggested that site-specific N-glycans on GluA2 regulate the intracellular trafficking and cell surface expression of AMPAR. 26271046 0 77 theme AMPA-Type 99:107 arg1 Receptors 119:127 AMPA-Type Glutamate Receptors 99:127 AMPA-Type Glutamate Receptors 99:127 Role of Site-Specific N-Glycans Expressed on GluA2 in the Regulation of Cell Surface Expression of AMPA-Type Glutamate Receptors. 26271046 1 78 theme nervous 337:343 arg1 system 345:350 the nervous system 333:350 the nervous system 333:350 The AMPA-type glutamate receptor (AMPAR), which is a tetrameric complex composed of four subunits (GluA1-4) with several combinations, mediates the majority of rapid excitatory synaptic transmissions in the nervous system. 26271046 2 79 theme expression 366:375 arg1 levels 377:382 Cell surface expression levels 353:382 Cell surface expression levels of AMPAR 353:391 Cell surface expression levels of AMPAR modulate synaptic plasticity, which is considered one of the molecular bases for learning and memory formation. 26271046 2 80 theme Cell 353:356 arg1 levels 377:382 Cell surface expression levels 353:382 Cell surface expression levels of AMPAR 353:391 Cell surface expression levels of AMPAR modulate synaptic plasticity, which is considered one of the molecular bases for learning and memory formation. 26271046 0 81 theme N-Glycans 22:30 arg1 Role 0:3 Role 0:3 Role of Site-Specific N-Glycans 0:30 Role of Site-Specific N-Glycans Expressed on GluA2 in the Regulation of Cell Surface Expression of AMPA-Type Glutamate Receptors. 26271046 6 82 theme potential 1042:1050 arg1 sites 1068:1072 potential N-glycosylation sites 1042:1072 potential N-glycosylation sites (N256, N370, N406, and N413) within GluA2 1042:1114 In the present study, using a series of mutants lacking potential N-glycosylation sites (N256, N370, N406, and N413) within GluA2, we demonstrated that the mutant lacking the N-glycan at N370 strongly suppressed the intracellular trafficking of GluA2 from the endoplasmic reticulum (ER) in HEK293 cells. 26271046 6 82 theme potential 1042:1050 arg1 N406 1087:1090 N406 1087:1090 N406 1087:1090 In the present study, using a series of mutants lacking potential N-glycosylation sites (N256, N370, N406, and N413) within GluA2, we demonstrated that the mutant lacking the N-glycan at N370 strongly suppressed the intracellular trafficking of GluA2 from the endoplasmic reticulum (ER) in HEK293 cells. 26271046 6 82 theme potential 1042:1050 arg1 N413 1097:1100 N413 1097:1100 N413 1097:1100 In the present study, using a series of mutants lacking potential N-glycosylation sites (N256, N370, N406, and N413) within GluA2, we demonstrated that the mutant lacking the N-glycan at N370 strongly suppressed the intracellular trafficking of GluA2 from the endoplasmic reticulum (ER) in HEK293 cells. 26271046 6 82 theme potential 1042:1050 arg1 N370 1081:1084 N370 1081:1084 N370 1081:1084 In the present study, using a series of mutants lacking potential N-glycosylation sites (N256, N370, N406, and N413) within GluA2, we demonstrated that the mutant lacking the N-glycan at N370 strongly suppressed the intracellular trafficking of GluA2 from the endoplasmic reticulum (ER) in HEK293 cells. 26271046 6 82 theme potential 1042:1050 arg1 N256 1075:1078 N256 1075:1078 N256 1075:1078 In the present study, using a series of mutants lacking potential N-glycosylation sites (N256, N370, N406, and N413) within GluA2, we demonstrated that the mutant lacking the N-glycan at N370 strongly suppressed the intracellular trafficking of GluA2 from the endoplasmic reticulum (ER) in HEK293 cells. 26271046 7 83 theme N370S 1420:1424 arg1 mutant 1426:1431 the GluA2 N370S mutant 1410:1431 the GluA2 N370S mutant 1410:1431 Cell surface expression of GluA1, which is a major subunit of AMPAR in neurons, was also suppressed by co-expression of the GluA2 N370S mutant. 26271046 3 84 theme maturation 740:749 arg1 process 751:757 the spine maturation process 730:757 the spine maturation process 730:757 To date, a unique trisaccharide (HSO3-3GlcAβ1-3Galβ1-4GlcNAc), human natural killer-1 (HNK-1) carbohydrate, was found expressed specifically on N-linked glycans of GluA2 and regulated the cell surface expression of AMPAR and the spine maturation process. 26271046 5 85 theme functions 975:983 arg1 regulation 955:964 the regulation 951:964 the regulation of AMPAR functions 951:983 Moreover, it is thought that other N-glycans on GluA2 also have potential roles in the regulation of AMPAR functions. 26271046 4 86 theme HNK-1 787:791 arg1 epitope 793:799 the HNK-1 epitope 783:799 the HNK-1 epitope on N-glycans of GluA2 783:821 However, evidence that the HNK-1 epitope on N-glycans of GluA2 directly affects these phenomena is lacking. 26271046 5 87 from N-glycans 903:911 arg1 GluA2 916:920 GluA2 916:920 GluA2 916:920 Moreover, it is thought that other N-glycans on GluA2 also have potential roles in the regulation of AMPAR functions. 26271046 1 88 theme rapid 290:294 arg1 transmissions 316:328 rapid excitatory synaptic transmissions 290:328 rapid excitatory synaptic transmissions 290:328 The AMPA-type glutamate receptor (AMPAR), which is a tetrameric complex composed of four subunits (GluA1-4) with several combinations, mediates the majority of rapid excitatory synaptic transmissions in the nervous system. 26271046 2 89 dep learning 474:481 arg1 formation 494:502 formation 494:502 formation 494:502 Cell surface expression levels of AMPAR modulate synaptic plasticity, which is considered one of the molecular bases for learning and memory formation. 26271046 9 90 theme cell 1724:1727 arg1 expression 1737:1746 enhanced cell surface expression 1715:1746 enhanced cell surface expression of GluA2 1715:1755 Moreover, we found that N413 was the main potential site of the HNK-1 epitope that promoted the interaction of GluA2 with N-cadherin, resulting in enhanced cell surface expression of GluA2. 26271046 6 91 from N370 1173:1176 arg1 N-glycan 1161:1168 the N-glycan at N370 1157:1176 the N-glycan at N370 1157:1176 In the present study, using a series of mutants lacking potential N-glycosylation sites (N256, N370, N406, and N413) within GluA2, we demonstrated that the mutant lacking the N-glycan at N370 strongly suppressed the intracellular trafficking of GluA2 from the endoplasmic reticulum (ER) in HEK293 cells. 26271046 6 91 from N370 1173:1176 arg1 at 1170:1171 the N-glycan at N370 1157:1176 the N-glycan at N370 1157:1176 In the present study, using a series of mutants lacking potential N-glycosylation sites (N256, N370, N406, and N413) within GluA2, we demonstrated that the mutant lacking the N-glycan at N370 strongly suppressed the intracellular trafficking of GluA2 from the endoplasmic reticulum (ER) in HEK293 cells. 26271046 1 92 with subunits 219:226 arg1 combinations 251:262 several combinations 243:262 several combinations 243:262 The AMPA-type glutamate receptor (AMPAR), which is a tetrameric complex composed of four subunits (GluA1-4) with several combinations, mediates the majority of rapid excitatory synaptic transmissions in the nervous system. 26271046 0 93 theme Glutamate 109:117 arg1 Receptors 119:127 AMPA-Type Glutamate Receptors 99:127 AMPA-Type Glutamate Receptors 99:127 Role of Site-Specific N-Glycans Expressed on GluA2 in the Regulation of Cell Surface Expression of AMPA-Type Glutamate Receptors. 26271046 3 94 link N-linked 649:656 arg1 glycans 658:664 N-linked glycans 649:664 N-linked glycans of GluA2 649:673 To date, a unique trisaccharide (HSO3-3GlcAβ1-3Galβ1-4GlcNAc), human natural killer-1 (HNK-1) carbohydrate, was found expressed specifically on N-linked glycans of GluA2 and regulated the cell surface expression of AMPAR and the spine maturation process. 26271046 3 95 theme GluA2 669:673 arg1 glycans 658:664 N-linked glycans 649:664 N-linked glycans of GluA2 649:673 To date, a unique trisaccharide (HSO3-3GlcAβ1-3Galβ1-4GlcNAc), human natural killer-1 (HNK-1) carbohydrate, was found expressed specifically on N-linked glycans of GluA2 and regulated the cell surface expression of AMPAR and the spine maturation process. 26271046 3 96 dep found 617:621 arg1 expressed 623:631 expressed 623:631 was found expressed specifically on N-linked glycans of GluA2 613:673 To date, a unique trisaccharide (HSO3-3GlcAβ1-3Galβ1-4GlcNAc), human natural killer-1 (HNK-1) carbohydrate, was found expressed specifically on N-linked glycans of GluA2 and regulated the cell surface expression of AMPAR and the spine maturation process. 27456536 7 0 theme overall 866:872 arg1 O-GlcNAc 874:881 overall O-GlcNAc 866:881 overall O-GlcNAc 866:881 We found that overall O-GlcNAc quickly increased and reached peak level at around 2 hrs post-stress, then returned to baseline levels after about 24 hrs. 27456536 4 1 theme oxidative 604:612 arg1 damage 614:619 oxidative damage 604:619 oxidative damage 604:619 However, many consider chronic stress, including oxidative damage as a major risk factor in the development of the disease. 27456536 1 2 link O-linked 98:105 arg1 modification 186:197 a dynamic post-translational modification 157:197 a dynamic post-translational modification occurring on the Ser/Thr residues of many intracellular proteins 157:262 O-linked β-N-acetlyglucosamine or O-GlcNAc modification is a dynamic post-translational modification occurring on the Ser/Thr residues of many intracellular proteins. 27456536 1 2 link O-linked 98:105 arg1 β-N-acetlyglucosamine 107:127 O-linked β-N-acetlyglucosamine 98:127 O-linked β-N-acetlyglucosamine 98:127 O-linked β-N-acetlyglucosamine or O-GlcNAc modification is a dynamic post-translational modification occurring on the Ser/Thr residues of many intracellular proteins. 27456536 1 2 link O-linked 98:105 arg1 modification 141:152 O-GlcNAc modification 132:152 O-GlcNAc modification 132:152 O-linked β-N-acetlyglucosamine or O-GlcNAc modification is a dynamic post-translational modification occurring on the Ser/Thr residues of many intracellular proteins. 27456536 7 3 theme hrs 936:938 arg1 post-stress 940:950 2 hrs post-stress 934:950 2 hrs post-stress 934:950 We found that overall O-GlcNAc quickly increased and reached peak level at around 2 hrs post-stress, then returned to baseline levels after about 24 hrs. 27456536 10 4 from O-GlcNAc 1401:1408 arg1 proteins 1437:1444 tau proteins 1433:1444 tau proteins 1433:1444 Furthermore, oxidative stress changes the dynamic balance between O-GlcNAc and phosphorylation on tau proteins. 27456536 8 5 from S262 1076:1079 arg1 phosphorylation 1052:1066 tau protein phosphorylation 1040:1066 tau protein phosphorylation at site S262 1040:1079 Interestingly, we also found that tau protein phosphorylation at site S262 showed parallel, whereas at S199 and PHF1 sites showed inverse dynamic to O-Glycosylation. 27456536 10 6 theme dynamic 1377:1383 arg1 balance 1385:1391 the dynamic balance 1373:1391 the dynamic balance between O-GlcNAc and phosphorylation on tau proteins 1373:1444 Furthermore, oxidative stress changes the dynamic balance between O-GlcNAc and phosphorylation on tau proteins. 27456536 10 7 theme oxidative 1348:1356 arg1 stress 1358:1363 oxidative stress 1348:1363 oxidative stress 1348:1363 Furthermore, oxidative stress changes the dynamic balance between O-GlcNAc and phosphorylation on tau proteins. 27456536 8 8 theme S199 1109:1112 arg1 sites 1123:1127 S199 and PHF1 sites 1109:1127 S199 and PHF1 sites 1109:1127 Interestingly, we also found that tau protein phosphorylation at site S262 showed parallel, whereas at S199 and PHF1 sites showed inverse dynamic to O-Glycosylation. 27456536 7 9 dep increased 891:899 arg1 returned 958:965 returned 958:965 returned to baseline levels after about 24 hrs 958:1003 We found that overall O-GlcNAc quickly increased and reached peak level at around 2 hrs post-stress, then returned to baseline levels after about 24 hrs. 27456536 5 10 theme O-GlcNAc 769:776 arg1 nature 759:764 the dynamic nature 747:764 the dynamic nature of O-GlcNAc 747:776 In this study, using the neuronal cell line SH-SY5Y we investigated the dynamic nature of O-GlcNAc after treatment with 0.5 mM H2 O2 for 30 min. 27456536 9 11 theme -induced 1266:1273 arg1 stress 1285:1290 H2 O2 -induced oxidative stress 1260:1290 H2 O2 -induced oxidative stress 1260:1290 In conclusion, our results show that temporary elevation in O-GlcNAc modification after H2 O2 -induced oxidative stress is detectable in cells of neuronal origin. 27456536 2 12 theme tau 327:329 arg1 protein 331:337 tau protein 327:337 tau protein 327:337 The chronic imbalance between phosphorylation and O-GlcNAc on tau protein is considered as one of the main hallmarks of Alzheimer's disease. 27456536 4 13 theme disease 670:676 arg1 development 651:661 the development 647:661 the development of the disease 647:676 However, many consider chronic stress, including oxidative damage as a major risk factor in the development of the disease. 27456536 8 14 theme PHF1 1118:1121 arg1 sites 1123:1127 S199 and PHF1 sites 1109:1127 S199 and PHF1 sites 1109:1127 Interestingly, we also found that tau protein phosphorylation at site S262 showed parallel, whereas at S199 and PHF1 sites showed inverse dynamic to O-Glycosylation. 27456536 9 15 theme oxidative 1275:1283 arg1 stress 1285:1290 H2 O2 -induced oxidative stress 1260:1290 H2 O2 -induced oxidative stress 1260:1290 In conclusion, our results show that temporary elevation in O-GlcNAc modification after H2 O2 -induced oxidative stress is detectable in cells of neuronal origin. 27456536 9 16 from cells 1309:1313 arg1 detectable 1295:1304 detectable 1295:1304 detectable 1295:1304 In conclusion, our results show that temporary elevation in O-GlcNAc modification after H2 O2 -induced oxidative stress is detectable in cells of neuronal origin. 27456536 5 17 with treatment 784:792 arg1 H2 806:807 0.5 mM H2 O2 799:810 0.5 mM H2 O2 799:810 In this study, using the neuronal cell line SH-SY5Y we investigated the dynamic nature of O-GlcNAc after treatment with 0.5 mM H2 O2 for 30 min. 27456536 2 18 from imbalance 277:285 arg1 protein 331:337 tau protein 327:337 tau protein 327:337 The chronic imbalance between phosphorylation and O-GlcNAc on tau protein is considered as one of the main hallmarks of Alzheimer's disease. 27456536 5 19 theme mM 803:804 arg1 H2 806:807 0.5 mM H2 O2 799:810 0.5 mM H2 O2 799:810 In this study, using the neuronal cell line SH-SY5Y we investigated the dynamic nature of O-GlcNAc after treatment with 0.5 mM H2 O2 for 30 min. 27456536 0 20 theme SH-SY5Y 83:89 arg1 cells 91:95 SH-SY5Y cells 83:95 SH-SY5Y cells 83:95 Oxidative stress induces transient O-GlcNAc elevation and tau dephosphorylation in SH-SY5Y cells. 27456536 10 21 theme tau 1433:1435 arg1 proteins 1437:1444 tau proteins 1433:1444 tau proteins 1433:1444 Furthermore, oxidative stress changes the dynamic balance between O-GlcNAc and phosphorylation on tau proteins. 27456536 5 22 theme dynamic 751:757 arg1 nature 759:764 the dynamic nature 747:764 the dynamic nature of O-GlcNAc 747:776 In this study, using the neuronal cell line SH-SY5Y we investigated the dynamic nature of O-GlcNAc after treatment with 0.5 mM H2 O2 for 30 min. 27456536 1 23 theme Ser/Thr 216:222 arg1 residues 224:231 the Ser/Thr residues 212:231 the Ser/Thr residues of many intracellular proteins 212:262 O-linked β-N-acetlyglucosamine or O-GlcNAc modification is a dynamic post-translational modification occurring on the Ser/Thr residues of many intracellular proteins. 27456536 1 23 theme Ser/Thr 216:222 arg1 proteins 255:262 many intracellular proteins 236:262 many intracellular proteins 236:262 O-linked β-N-acetlyglucosamine or O-GlcNAc modification is a dynamic post-translational modification occurring on the Ser/Thr residues of many intracellular proteins. 27456536 0 24 theme Oxidative 0:8 arg1 stress 10:15 Oxidative stress 0:15 Oxidative stress 0:15 Oxidative stress induces transient O-GlcNAc elevation and tau dephosphorylation in SH-SY5Y cells. 27456536 4 25 theme chronic 578:584 arg1 stress 586:591 chronic stress 578:591 chronic stress 578:591 However, many consider chronic stress, including oxidative damage as a major risk factor in the development of the disease. 27456536 4 25 theme chronic 578:584 arg1 factor 637:642 a major risk factor 624:642 a major risk factor in the development of the disease 624:676 However, many consider chronic stress, including oxidative damage as a major risk factor in the development of the disease. 27456536 9 26 from detectable 1295:1304 arg1 cells 1309:1313 cells 1309:1313 cells of neuronal origin 1309:1332 In conclusion, our results show that temporary elevation in O-GlcNAc modification after H2 O2 -induced oxidative stress is detectable in cells of neuronal origin. 27456536 1 27 theme O-linked 98:105 arg1 modification 186:197 a dynamic post-translational modification 157:197 a dynamic post-translational modification occurring on the Ser/Thr residues of many intracellular proteins 157:262 O-linked β-N-acetlyglucosamine or O-GlcNAc modification is a dynamic post-translational modification occurring on the Ser/Thr residues of many intracellular proteins. 27456536 1 27 theme O-linked 98:105 arg1 β-N-acetlyglucosamine 107:127 O-linked β-N-acetlyglucosamine 98:127 O-linked β-N-acetlyglucosamine 98:127 O-linked β-N-acetlyglucosamine or O-GlcNAc modification is a dynamic post-translational modification occurring on the Ser/Thr residues of many intracellular proteins. 27456536 1 27 theme O-linked 98:105 arg1 modification 141:152 O-GlcNAc modification 132:152 O-GlcNAc modification 132:152 O-linked β-N-acetlyglucosamine or O-GlcNAc modification is a dynamic post-translational modification occurring on the Ser/Thr residues of many intracellular proteins. 27456536 3 28 theme O-GlcNAc 453:460 arg1 levels 462:467 O-GlcNAc levels 453:467 O-GlcNAc levels 453:467 In recent years, many studies also showed that O-GlcNAc levels can elevate upon acute stress and suggested that this might facilitate cell survival. 27456536 0 29 theme transient 25:33 arg1 elevation 44:52 transient O-GlcNAc elevation 25:52 transient O-GlcNAc elevation 25:52 Oxidative stress induces transient O-GlcNAc elevation and tau dephosphorylation in SH-SY5Y cells. 27456536 8 30 theme tau 1040:1042 arg1 phosphorylation 1052:1066 tau protein phosphorylation 1040:1066 tau protein phosphorylation at site S262 1040:1079 Interestingly, we also found that tau protein phosphorylation at site S262 showed parallel, whereas at S199 and PHF1 sites showed inverse dynamic to O-Glycosylation. 27456536 7 31 theme peak 913:916 arg1 level 918:922 peak level 913:922 peak level 913:922 We found that overall O-GlcNAc quickly increased and reached peak level at around 2 hrs post-stress, then returned to baseline levels after about 24 hrs. 27456536 3 32 theme acute 486:490 arg1 stress 492:497 acute stress 486:497 acute stress 486:497 In recent years, many studies also showed that O-GlcNAc levels can elevate upon acute stress and suggested that this might facilitate cell survival. 27456536 3 33 theme recent 409:414 arg1 years 416:420 recent years 409:420 recent years 409:420 In recent years, many studies also showed that O-GlcNAc levels can elevate upon acute stress and suggested that this might facilitate cell survival. 27456536 10 34 from phosphorylation 1414:1428 arg1 proteins 1437:1444 tau proteins 1433:1444 tau proteins 1433:1444 Furthermore, oxidative stress changes the dynamic balance between O-GlcNAc and phosphorylation on tau proteins. 27456536 5 35 theme neuronal 704:711 arg1 line 718:721 the neuronal cell line 700:721 the neuronal cell line SH-SY5Y 700:729 In this study, using the neuronal cell line SH-SY5Y we investigated the dynamic nature of O-GlcNAc after treatment with 0.5 mM H2 O2 for 30 min. 27456536 1 36 theme many 236:239 arg1 proteins 255:262 many intracellular proteins 236:262 many intracellular proteins 236:262 O-linked β-N-acetlyglucosamine or O-GlcNAc modification is a dynamic post-translational modification occurring on the Ser/Thr residues of many intracellular proteins. 27456536 5 37 theme cell 713:716 arg1 line 718:721 the neuronal cell line 700:721 the neuronal cell line SH-SY5Y 700:729 In this study, using the neuronal cell line SH-SY5Y we investigated the dynamic nature of O-GlcNAc after treatment with 0.5 mM H2 O2 for 30 min. 27456536 1 38 theme intracellular 241:253 arg1 proteins 255:262 many intracellular proteins 236:262 many intracellular proteins 236:262 O-linked β-N-acetlyglucosamine or O-GlcNAc modification is a dynamic post-translational modification occurring on the Ser/Thr residues of many intracellular proteins. 27456536 0 39 theme O-GlcNAc 35:42 arg1 elevation 44:52 transient O-GlcNAc elevation 25:52 transient O-GlcNAc elevation 25:52 Oxidative stress induces transient O-GlcNAc elevation and tau dephosphorylation in SH-SY5Y cells. 27456536 8 40 theme protein 1044:1050 arg1 phosphorylation 1052:1066 tau protein phosphorylation 1040:1066 tau protein phosphorylation at site S262 1040:1079 Interestingly, we also found that tau protein phosphorylation at site S262 showed parallel, whereas at S199 and PHF1 sites showed inverse dynamic to O-Glycosylation. 27456536 6 41 theme oxidative 834:842 arg1 stress 844:849 oxidative stress 834:849 oxidative stress 834:849 to induce oxidative stress. 27456536 2 42 theme chronic 269:275 arg1 hallmarks 372:380 the main hallmarks 363:380 the main hallmarks of Alzheimer's disease 363:403 The chronic imbalance between phosphorylation and O-GlcNAc on tau protein is considered as one of the main hallmarks of Alzheimer's disease. 27456536 2 42 theme chronic 269:275 arg1 imbalance 277:285 The chronic imbalance 265:285 The chronic imbalance between phosphorylation and O-GlcNAc on tau protein 265:337 The chronic imbalance between phosphorylation and O-GlcNAc on tau protein is considered as one of the main hallmarks of Alzheimer's disease. 27456536 2 42 theme chronic 269:275 arg1 one 356:358 one 356:358 one 356:358 The chronic imbalance between phosphorylation and O-GlcNAc on tau protein is considered as one of the main hallmarks of Alzheimer's disease. 27456536 1 43 theme proteins 255:262 arg1 residues 224:231 the Ser/Thr residues 212:231 the Ser/Thr residues of many intracellular proteins 212:262 O-linked β-N-acetlyglucosamine or O-GlcNAc modification is a dynamic post-translational modification occurring on the Ser/Thr residues of many intracellular proteins. 27456536 1 43 theme proteins 255:262 arg1 proteins 255:262 many intracellular proteins 236:262 many intracellular proteins 236:262 O-linked β-N-acetlyglucosamine or O-GlcNAc modification is a dynamic post-translational modification occurring on the Ser/Thr residues of many intracellular proteins. 27456536 0 44 theme tau 58:60 arg1 dephosphorylation 62:78 tau dephosphorylation 58:78 tau dephosphorylation 58:78 Oxidative stress induces transient O-GlcNAc elevation and tau dephosphorylation in SH-SY5Y cells. 27456536 9 45 theme neuronal 1318:1325 arg1 origin 1327:1332 neuronal origin 1318:1332 neuronal origin 1318:1332 In conclusion, our results show that temporary elevation in O-GlcNAc modification after H2 O2 -induced oxidative stress is detectable in cells of neuronal origin. 27456536 8 46 theme site 1071:1074 arg1 S262 1076:1079 site S262 1071:1079 site S262 1071:1079 Interestingly, we also found that tau protein phosphorylation at site S262 showed parallel, whereas at S199 and PHF1 sites showed inverse dynamic to O-Glycosylation. 27456536 5 47 dep line 718:721 arg1 SH-SY5Y 723:729 SH-SY5Y 723:729 the neuronal cell line SH-SY5Y 700:729 In this study, using the neuronal cell line SH-SY5Y we investigated the dynamic nature of O-GlcNAc after treatment with 0.5 mM H2 O2 for 30 min. 27456536 1 48 theme O-GlcNAc 132:139 arg1 β-N-acetlyglucosamine 107:127 O-linked β-N-acetlyglucosamine 98:127 O-linked β-N-acetlyglucosamine 98:127 O-linked β-N-acetlyglucosamine or O-GlcNAc modification is a dynamic post-translational modification occurring on the Ser/Thr residues of many intracellular proteins. 27456536 1 48 theme O-GlcNAc 132:139 arg1 modification 186:197 a dynamic post-translational modification 157:197 a dynamic post-translational modification occurring on the Ser/Thr residues of many intracellular proteins 157:262 O-linked β-N-acetlyglucosamine or O-GlcNAc modification is a dynamic post-translational modification occurring on the Ser/Thr residues of many intracellular proteins. 27456536 1 48 theme O-GlcNAc 132:139 arg1 modification 141:152 O-GlcNAc modification 132:152 O-GlcNAc modification 132:152 O-linked β-N-acetlyglucosamine or O-GlcNAc modification is a dynamic post-translational modification occurring on the Ser/Thr residues of many intracellular proteins. 27456536 5 49 theme 0.5 799:801 arg1 mM 803:804 mM 803:804 mM 803:804 In this study, using the neuronal cell line SH-SY5Y we investigated the dynamic nature of O-GlcNAc after treatment with 0.5 mM H2 O2 for 30 min. 27456536 9 50 theme origin 1327:1332 arg1 cells 1309:1313 cells 1309:1313 cells of neuronal origin 1309:1332 In conclusion, our results show that temporary elevation in O-GlcNAc modification after H2 O2 -induced oxidative stress is detectable in cells of neuronal origin. 27456536 9 51 theme temporary 1209:1217 arg1 elevation 1219:1227 temporary elevation 1209:1227 temporary elevation in O-GlcNAc modification after H2 O2 -induced oxidative stress 1209:1290 In conclusion, our results show that temporary elevation in O-GlcNAc modification after H2 O2 -induced oxidative stress is detectable in cells of neuronal origin. 27456536 7 52 theme baseline 970:977 arg1 levels 979:984 baseline levels 970:984 baseline levels 970:984 We found that overall O-GlcNAc quickly increased and reached peak level at around 2 hrs post-stress, then returned to baseline levels after about 24 hrs. 27456536 2 53 theme hallmarks 372:380 arg1 hallmarks 372:380 the main hallmarks 363:380 the main hallmarks of Alzheimer's disease 363:403 The chronic imbalance between phosphorylation and O-GlcNAc on tau protein is considered as one of the main hallmarks of Alzheimer's disease. 27456536 2 53 theme hallmarks 372:380 arg1 imbalance 277:285 The chronic imbalance 265:285 The chronic imbalance between phosphorylation and O-GlcNAc on tau protein 265:337 The chronic imbalance between phosphorylation and O-GlcNAc on tau protein is considered as one of the main hallmarks of Alzheimer's disease. 27456536 2 53 theme hallmarks 372:380 arg1 one 356:358 one 356:358 one 356:358 The chronic imbalance between phosphorylation and O-GlcNAc on tau protein is considered as one of the main hallmarks of Alzheimer's disease. 27456536 1 54 theme dynamic 159:165 arg1 β-N-acetlyglucosamine 107:127 O-linked β-N-acetlyglucosamine 98:127 O-linked β-N-acetlyglucosamine 98:127 O-linked β-N-acetlyglucosamine or O-GlcNAc modification is a dynamic post-translational modification occurring on the Ser/Thr residues of many intracellular proteins. 27456536 1 54 theme dynamic 159:165 arg1 modification 186:197 a dynamic post-translational modification 157:197 a dynamic post-translational modification occurring on the Ser/Thr residues of many intracellular proteins 157:262 O-linked β-N-acetlyglucosamine or O-GlcNAc modification is a dynamic post-translational modification occurring on the Ser/Thr residues of many intracellular proteins. 27456536 1 54 theme dynamic 159:165 arg1 modification 141:152 O-GlcNAc modification 132:152 O-GlcNAc modification 132:152 O-linked β-N-acetlyglucosamine or O-GlcNAc modification is a dynamic post-translational modification occurring on the Ser/Thr residues of many intracellular proteins. 27456536 2 55 theme main 367:370 arg1 hallmarks 372:380 the main hallmarks 363:380 the main hallmarks of Alzheimer's disease 363:403 The chronic imbalance between phosphorylation and O-GlcNAc on tau protein is considered as one of the main hallmarks of Alzheimer's disease. 27456536 4 56 theme major 626:630 arg1 stress 586:591 chronic stress 578:591 chronic stress 578:591 However, many consider chronic stress, including oxidative damage as a major risk factor in the development of the disease. 27456536 4 56 theme major 626:630 arg1 factor 637:642 a major risk factor 624:642 a major risk factor in the development of the disease 624:676 However, many consider chronic stress, including oxidative damage as a major risk factor in the development of the disease. 27456536 9 57 from elevation 1219:1227 arg1 modification 1241:1252 O-GlcNAc modification 1232:1252 O-GlcNAc modification 1232:1252 In conclusion, our results show that temporary elevation in O-GlcNAc modification after H2 O2 -induced oxidative stress is detectable in cells of neuronal origin. 27456536 4 58 from factor 637:642 arg1 development 651:661 the development 647:661 the development of the disease 647:676 However, many consider chronic stress, including oxidative damage as a major risk factor in the development of the disease. 27456536 3 59 theme cell 540:543 arg1 survival 545:552 cell survival 540:552 cell survival 540:552 In recent years, many studies also showed that O-GlcNAc levels can elevate upon acute stress and suggested that this might facilitate cell survival. 27456536 3 60 theme many 423:426 arg1 studies 428:434 many studies 423:434 many studies 423:434 In recent years, many studies also showed that O-GlcNAc levels can elevate upon acute stress and suggested that this might facilitate cell survival. 27456536 9 61 theme O-GlcNAc 1232:1239 arg1 modification 1241:1252 O-GlcNAc modification 1232:1252 O-GlcNAc modification 1232:1252 In conclusion, our results show that temporary elevation in O-GlcNAc modification after H2 O2 -induced oxidative stress is detectable in cells of neuronal origin. 27456536 1 62 theme post-translational 167:184 arg1 β-N-acetlyglucosamine 107:127 O-linked β-N-acetlyglucosamine 98:127 O-linked β-N-acetlyglucosamine 98:127 O-linked β-N-acetlyglucosamine or O-GlcNAc modification is a dynamic post-translational modification occurring on the Ser/Thr residues of many intracellular proteins. 27456536 1 62 theme post-translational 167:184 arg1 modification 186:197 a dynamic post-translational modification 157:197 a dynamic post-translational modification occurring on the Ser/Thr residues of many intracellular proteins 157:262 O-linked β-N-acetlyglucosamine or O-GlcNAc modification is a dynamic post-translational modification occurring on the Ser/Thr residues of many intracellular proteins. 27456536 1 62 theme post-translational 167:184 arg1 modification 141:152 O-GlcNAc modification 132:152 O-GlcNAc modification 132:152 O-linked β-N-acetlyglucosamine or O-GlcNAc modification is a dynamic post-translational modification occurring on the Ser/Thr residues of many intracellular proteins. 27456536 4 63 theme risk 632:635 arg1 stress 586:591 chronic stress 578:591 chronic stress 578:591 However, many consider chronic stress, including oxidative damage as a major risk factor in the development of the disease. 27456536 4 63 theme risk 632:635 arg1 factor 637:642 a major risk factor 624:642 a major risk factor in the development of the disease 624:676 However, many consider chronic stress, including oxidative damage as a major risk factor in the development of the disease. 25053479 1 0 from POGLUT1 335:341 arg1 human 346:350 human 346:350 human 346:350 One of the evolutionarily conserved posttranslational modifications of the Notch receptors is the addition of an O-linked glucose to epidermal growth factor-like (EGF) repeats with a specific consensus sequence by the protein O-glucosyltransferase Rumi (POGLUT1 in human). 25053479 3 1 theme Drosophila 690:699 arg1 Notch 701:705 Drosophila Notch 690:705 Drosophila Notch 690:705 To demonstrate that the Notch receptor itself is the biologically relevant target of Rumi in flies, and to determine the role of the 18 Rumi target sites on Notch in regulating Notch signaling, we have performed an in vivo structure-function analysis of Drosophila Notch. 25053479 1 2 theme consensus 273:281 arg1 sequence 283:290 a specific consensus sequence 262:290 a specific consensus sequence by the protein O-glucosyltransferase Rumi (POGLUT1 in human) 262:351 One of the evolutionarily conserved posttranslational modifications of the Notch receptors is the addition of an O-linked glucose to epidermal growth factor-like (EGF) repeats with a specific consensus sequence by the protein O-glucosyltransferase Rumi (POGLUT1 in human). 25053479 5 3 theme transgenes 872:881 arg1 insertion 859:867 random insertion 852:867 random insertion of transgenes 852:881 To avoid the potential artifacts associated with overexpression of Notch and random insertion of transgenes, we have used recombineering and site-specific integration technologies, which have been adapted for usage in Drosophila in recent years. 25053479 5 3 theme transgenes 872:881 arg1 overexpression 824:837 overexpression 824:837 overexpression of Notch 824:846 To avoid the potential artifacts associated with overexpression of Notch and random insertion of transgenes, we have used recombineering and site-specific integration technologies, which have been adapted for usage in Drosophila in recent years. 25053479 7 4 from experiments 1222:1232 arg1 animals 1237:1243 animals 1237:1243 animals raised at various temperatures 1237:1274 Gene dosage and rescue experiments in animals raised at various temperatures allowed us to dissect the contribution of O-glucosylation sites to the regulation of the Notch signaling strength. 25053479 2 5 from Loss 354:357 arg1 flies 370:374 flies 370:374 flies 370:374 Loss of rumi in flies results in a temperature-sensitive loss of Notch signaling. 25053479 7 6 theme strength 1381:1388 arg1 regulation 1347:1356 the regulation 1343:1356 the regulation of the Notch signaling strength 1343:1388 Gene dosage and rescue experiments in animals raised at various temperatures allowed us to dissect the contribution of O-glucosylation sites to the regulation of the Notch signaling strength. 25053479 1 7 theme glucose 203:209 arg1 One 81:83 One 81:83 One 81:83 One of the evolutionarily conserved posttranslational modifications of the Notch receptors is the addition of an O-linked glucose to epidermal growth factor-like (EGF) repeats with a specific consensus sequence by the protein O-glucosyltransferase Rumi (POGLUT1 in human). 25053479 1 7 theme glucose 203:209 arg1 modifications 135:147 the evolutionarily conserved posttranslational modifications 88:147 the evolutionarily conserved posttranslational modifications of the Notch receptors 88:170 One of the evolutionarily conserved posttranslational modifications of the Notch receptors is the addition of an O-linked glucose to epidermal growth factor-like (EGF) repeats with a specific consensus sequence by the protein O-glucosyltransferase Rumi (POGLUT1 in human). 25053479 1 7 theme glucose 203:209 arg1 addition 179:186 the addition 175:186 the addition of an O-linked glucose to epidermal growth factor-like (EGF) repeats with a specific consensus sequence by the protein O-glucosyltransferase Rumi (POGLUT1 in human) 175:351 One of the evolutionarily conserved posttranslational modifications of the Notch receptors is the addition of an O-linked glucose to epidermal growth factor-like (EGF) repeats with a specific consensus sequence by the protein O-glucosyltransferase Rumi (POGLUT1 in human). 25053479 6 8 theme transgenes 1112:1121 arg1 series 1088:1093 a series 1086:1093 a series of Notch genomic transgenes which harbor mutations in all or specific subsets of Notch O-glucose sites 1086:1196 Using gene synthesis and site-directed mutagenesis, we generated a series of Notch genomic transgenes which harbor mutations in all or specific subsets of Notch O-glucose sites. 25053479 5 9 from usage 984:988 arg1 Drosophila 993:1002 Drosophila 993:1002 Drosophila 993:1002 To avoid the potential artifacts associated with overexpression of Notch and random insertion of transgenes, we have used recombineering and site-specific integration technologies, which have been adapted for usage in Drosophila in recent years. 25053479 5 9 from usage 984:988 arg1 years 1014:1018 recent years 1007:1018 recent years 1007:1018 To avoid the potential artifacts associated with overexpression of Notch and random insertion of transgenes, we have used recombineering and site-specific integration technologies, which have been adapted for usage in Drosophila in recent years. 25053479 5 10 theme potential 788:796 arg1 artifacts 798:806 the potential artifacts 784:806 the potential artifacts associated with overexpression of Notch and random insertion of transgenes 784:881 To avoid the potential artifacts associated with overexpression of Notch and random insertion of transgenes, we have used recombineering and site-specific integration technologies, which have been adapted for usage in Drosophila in recent years. 25053479 3 11 theme Rumi 572:575 arg1 sites 584:588 the 18 Rumi target sites 565:588 the 18 Rumi target sites on Notch 565:597 To demonstrate that the Notch receptor itself is the biologically relevant target of Rumi in flies, and to determine the role of the 18 Rumi target sites on Notch in regulating Notch signaling, we have performed an in vivo structure-function analysis of Drosophila Notch. 25053479 1 12 theme factor-like 231:241 arg1 repeats 249:255 epidermal growth factor-like (EGF) repeats 214:255 epidermal growth factor-like (EGF) repeats with a specific consensus sequence by the protein O-glucosyltransferase Rumi (POGLUT1 in human) 214:351 One of the evolutionarily conserved posttranslational modifications of the Notch receptors is the addition of an O-linked glucose to epidermal growth factor-like (EGF) repeats with a specific consensus sequence by the protein O-glucosyltransferase Rumi (POGLUT1 in human). 25053479 6 13 theme sites 1192:1196 arg1 subsets 1165:1171 specific subsets 1156:1171 specific subsets of Notch O-glucose sites 1156:1196 Using gene synthesis and site-directed mutagenesis, we generated a series of Notch genomic transgenes which harbor mutations in all or specific subsets of Notch O-glucose sites. 25053479 6 13 theme sites 1192:1196 arg1 mutations 1136:1144 mutations 1136:1144 mutations in all 1136:1151 Using gene synthesis and site-directed mutagenesis, we generated a series of Notch genomic transgenes which harbor mutations in all or specific subsets of Notch O-glucose sites. 25053479 8 14 used used 1438:1441 arg2 methods 1408:1414 methods 1408:1414 methods 1408:1414 The reagents and methods presented here can be used to address similar questions about other posttranslational modifications of Notch or other Drosophila proteins. 25053479 8 14 used used 1438:1441 arg2 reagents 1395:1402 reagents 1395:1402 reagents 1395:1402 The reagents and methods presented here can be used to address similar questions about other posttranslational modifications of Notch or other Drosophila proteins. 25053479 5 15 theme recent 1007:1012 arg1 years 1014:1018 recent years 1007:1018 recent years 1007:1018 To avoid the potential artifacts associated with overexpression of Notch and random insertion of transgenes, we have used recombineering and site-specific integration technologies, which have been adapted for usage in Drosophila in recent years. 25053479 6 16 theme Notch 1176:1180 arg1 sites 1192:1196 Notch O-glucose sites 1176:1196 Notch O-glucose sites 1176:1196 Using gene synthesis and site-directed mutagenesis, we generated a series of Notch genomic transgenes which harbor mutations in all or specific subsets of Notch O-glucose sites. 25053479 7 17 theme sites 1334:1338 arg1 contribution 1302:1313 the contribution 1298:1313 the contribution of O-glucosylation sites to the regulation of the Notch signaling strength 1298:1388 Gene dosage and rescue experiments in animals raised at various temperatures allowed us to dissect the contribution of O-glucosylation sites to the regulation of the Notch signaling strength. 25053479 1 18 theme Notch 156:160 arg1 receptors 162:170 the Notch receptors 152:170 the Notch receptors 152:170 One of the evolutionarily conserved posttranslational modifications of the Notch receptors is the addition of an O-linked glucose to epidermal growth factor-like (EGF) repeats with a specific consensus sequence by the protein O-glucosyltransferase Rumi (POGLUT1 in human). 25053479 2 19 theme Notch 419:423 arg1 signaling 425:433 Notch signaling 419:433 Notch signaling 419:433 Loss of rumi in flies results in a temperature-sensitive loss of Notch signaling. 25053479 3 20 from role 557:560 arg1 Notch 593:597 Notch 593:597 Notch 593:597 To demonstrate that the Notch receptor itself is the biologically relevant target of Rumi in flies, and to determine the role of the 18 Rumi target sites on Notch in regulating Notch signaling, we have performed an in vivo structure-function analysis of Drosophila Notch. 25053479 7 21 theme Gene 1199:1202 arg1 dosage 1204:1209 Gene dosage 1199:1209 Gene dosage 1199:1209 Gene dosage and rescue experiments in animals raised at various temperatures allowed us to dissect the contribution of O-glucosylation sites to the regulation of the Notch signaling strength. 25053479 3 22 theme sites 584:588 arg1 role 557:560 the role 553:560 the role of the 18 Rumi target sites on Notch in regulating Notch signaling 553:627 To demonstrate that the Notch receptor itself is the biologically relevant target of Rumi in flies, and to determine the role of the 18 Rumi target sites on Notch in regulating Notch signaling, we have performed an in vivo structure-function analysis of Drosophila Notch. 25053479 5 23 theme random 852:857 arg1 insertion 859:867 random insertion 852:867 random insertion of transgenes 852:881 To avoid the potential artifacts associated with overexpression of Notch and random insertion of transgenes, we have used recombineering and site-specific integration technologies, which have been adapted for usage in Drosophila in recent years. 25053479 3 24 from flies 529:533 arg1 target 511:516 the biologically relevant target 485:516 the biologically relevant target of Rumi in flies 485:533 To demonstrate that the Notch receptor itself is the biologically relevant target of Rumi in flies, and to determine the role of the 18 Rumi target sites on Notch in regulating Notch signaling, we have performed an in vivo structure-function analysis of Drosophila Notch. 25053479 3 24 from flies 529:533 arg1 receptor 466:473 the Notch receptor 456:473 the Notch receptor itself 456:480 To demonstrate that the Notch receptor itself is the biologically relevant target of Rumi in flies, and to determine the role of the 18 Rumi target sites on Notch in regulating Notch signaling, we have performed an in vivo structure-function analysis of Drosophila Notch. 25053479 8 25 theme other 1478:1482 arg1 modifications 1502:1514 other posttranslational modifications 1478:1514 other posttranslational modifications of Notch or other Drosophila proteins 1478:1552 The reagents and methods presented here can be used to address similar questions about other posttranslational modifications of Notch or other Drosophila proteins. 25053479 1 26 theme posttranslational 117:133 arg1 modifications 135:147 the evolutionarily conserved posttranslational modifications 88:147 the evolutionarily conserved posttranslational modifications of the Notch receptors 88:170 One of the evolutionarily conserved posttranslational modifications of the Notch receptors is the addition of an O-linked glucose to epidermal growth factor-like (EGF) repeats with a specific consensus sequence by the protein O-glucosyltransferase Rumi (POGLUT1 in human). 25053479 1 27 link O-linked 194:201 arg1 glucose 203:209 an O-linked glucose 191:209 an O-linked glucose 191:209 One of the evolutionarily conserved posttranslational modifications of the Notch receptors is the addition of an O-linked glucose to epidermal growth factor-like (EGF) repeats with a specific consensus sequence by the protein O-glucosyltransferase Rumi (POGLUT1 in human). 25053479 3 28 from sites 584:588 arg1 Notch 593:597 Notch 593:597 Notch 593:597 To demonstrate that the Notch receptor itself is the biologically relevant target of Rumi in flies, and to determine the role of the 18 Rumi target sites on Notch in regulating Notch signaling, we have performed an in vivo structure-function analysis of Drosophila Notch. 25053479 8 29 theme Notch 1519:1523 arg1 modifications 1502:1514 other posttranslational modifications 1478:1514 other posttranslational modifications of Notch or other Drosophila proteins 1478:1552 The reagents and methods presented here can be used to address similar questions about other posttranslational modifications of Notch or other Drosophila proteins. 25053479 3 30 from Notch 593:597 arg1 role 557:560 the role 553:560 the role of the 18 Rumi target sites on Notch in regulating Notch signaling 553:627 To demonstrate that the Notch receptor itself is the biologically relevant target of Rumi in flies, and to determine the role of the 18 Rumi target sites on Notch in regulating Notch signaling, we have performed an in vivo structure-function analysis of Drosophila Notch. 25053479 0 31 theme Structure-function 0:17 arg1 analysis 19:26 Structure-function analysis 0:26 Structure-function analysis of Drosophila Notch 0:46 Structure-function analysis of Drosophila Notch using genomic rescue transgenes. 25053479 5 32 theme recombineering 897:910 arg1 technologies 942:953 recombineering and site-specific integration technologies 897:953 recombineering and site-specific integration technologies 897:953 To avoid the potential artifacts associated with overexpression of Notch and random insertion of transgenes, we have used recombineering and site-specific integration technologies, which have been adapted for usage in Drosophila in recent years. 25053479 6 33 theme gene 1027:1030 arg1 synthesis 1032:1040 gene synthesis 1027:1040 gene synthesis 1027:1040 Using gene synthesis and site-directed mutagenesis, we generated a series of Notch genomic transgenes which harbor mutations in all or specific subsets of Notch O-glucose sites. 25053479 8 34 theme other 1528:1532 arg1 proteins 1545:1552 other Drosophila proteins 1528:1552 other Drosophila proteins 1528:1552 The reagents and methods presented here can be used to address similar questions about other posttranslational modifications of Notch or other Drosophila proteins. 25053479 3 35 theme Notch 460:464 arg1 target 511:516 the biologically relevant target 485:516 the biologically relevant target of Rumi in flies 485:533 To demonstrate that the Notch receptor itself is the biologically relevant target of Rumi in flies, and to determine the role of the 18 Rumi target sites on Notch in regulating Notch signaling, we have performed an in vivo structure-function analysis of Drosophila Notch. 25053479 3 35 theme Notch 460:464 arg1 receptor 466:473 the Notch receptor 456:473 the Notch receptor itself 456:480 To demonstrate that the Notch receptor itself is the biologically relevant target of Rumi in flies, and to determine the role of the 18 Rumi target sites on Notch in regulating Notch signaling, we have performed an in vivo structure-function analysis of Drosophila Notch. 25053479 5 36 theme site-specific 916:928 arg1 integration 930:940 site-specific integration 916:940 site-specific integration 916:940 To avoid the potential artifacts associated with overexpression of Notch and random insertion of transgenes, we have used recombineering and site-specific integration technologies, which have been adapted for usage in Drosophila in recent years. 25053479 8 37 theme proteins 1545:1552 arg1 modifications 1502:1514 other posttranslational modifications 1478:1514 other posttranslational modifications of Notch or other Drosophila proteins 1478:1552 The reagents and methods presented here can be used to address similar questions about other posttranslational modifications of Notch or other Drosophila proteins. 25053479 0 38 theme Notch 42:46 arg1 analysis 19:26 Structure-function analysis 0:26 Structure-function analysis of Drosophila Notch 0:46 Structure-function analysis of Drosophila Notch using genomic rescue transgenes. 25053479 1 39 theme O-glucosyltransferase 307:327 arg1 Rumi 329:332 the protein O-glucosyltransferase Rumi 295:332 the protein O-glucosyltransferase Rumi (POGLUT1 in human) 295:351 One of the evolutionarily conserved posttranslational modifications of the Notch receptors is the addition of an O-linked glucose to epidermal growth factor-like (EGF) repeats with a specific consensus sequence by the protein O-glucosyltransferase Rumi (POGLUT1 in human). 25053479 1 39 theme O-glucosyltransferase 307:327 arg1 POGLUT1 335:341 POGLUT1 335:341 POGLUT1 335:341 One of the evolutionarily conserved posttranslational modifications of the Notch receptors is the addition of an O-linked glucose to epidermal growth factor-like (EGF) repeats with a specific consensus sequence by the protein O-glucosyltransferase Rumi (POGLUT1 in human). 25053479 6 40 from mutations 1136:1144 arg1 all 1149:1151 all 1149:1151 all 1149:1151 Using gene synthesis and site-directed mutagenesis, we generated a series of Notch genomic transgenes which harbor mutations in all or specific subsets of Notch O-glucose sites. 25053479 0 41 theme genomic 54:60 arg1 transgenes 69:78 genomic rescue transgenes 54:78 genomic rescue transgenes 54:78 Structure-function analysis of Drosophila Notch using genomic rescue transgenes. 25053479 6 42 theme specific 1156:1163 arg1 subsets 1165:1171 specific subsets 1156:1171 specific subsets of Notch O-glucose sites 1156:1196 Using gene synthesis and site-directed mutagenesis, we generated a series of Notch genomic transgenes which harbor mutations in all or specific subsets of Notch O-glucose sites. 25053479 3 43 theme structure-function 659:676 arg1 analysis 678:685 an in vivo structure-function analysis 648:685 an in vivo structure-function analysis of Drosophila Notch 648:705 To demonstrate that the Notch receptor itself is the biologically relevant target of Rumi in flies, and to determine the role of the 18 Rumi target sites on Notch in regulating Notch signaling, we have performed an in vivo structure-function analysis of Drosophila Notch. 25053479 3 44 theme relevant 502:509 arg1 target 511:516 the biologically relevant target 485:516 the biologically relevant target of Rumi in flies 485:533 To demonstrate that the Notch receptor itself is the biologically relevant target of Rumi in flies, and to determine the role of the 18 Rumi target sites on Notch in regulating Notch signaling, we have performed an in vivo structure-function analysis of Drosophila Notch. 25053479 3 44 theme relevant 502:509 arg1 receptor 466:473 the Notch receptor 456:473 the Notch receptor itself 456:480 To demonstrate that the Notch receptor itself is the biologically relevant target of Rumi in flies, and to determine the role of the 18 Rumi target sites on Notch in regulating Notch signaling, we have performed an in vivo structure-function analysis of Drosophila Notch. 25053479 7 45 from dosage 1204:1209 arg1 animals 1237:1243 animals 1237:1243 animals raised at various temperatures 1237:1274 Gene dosage and rescue experiments in animals raised at various temperatures allowed us to dissect the contribution of O-glucosylation sites to the regulation of the Notch signaling strength. 25053479 3 46 theme in 651:652 arg1 analysis 678:685 an in vivo structure-function analysis 648:685 an in vivo structure-function analysis of Drosophila Notch 648:705 To demonstrate that the Notch receptor itself is the biologically relevant target of Rumi in flies, and to determine the role of the 18 Rumi target sites on Notch in regulating Notch signaling, we have performed an in vivo structure-function analysis of Drosophila Notch. 25053479 3 47 from target 511:516 arg1 flies 529:533 flies 529:533 flies 529:533 To demonstrate that the Notch receptor itself is the biologically relevant target of Rumi in flies, and to determine the role of the 18 Rumi target sites on Notch in regulating Notch signaling, we have performed an in vivo structure-function analysis of Drosophila Notch. 25053479 1 48 theme specific 264:271 arg1 sequence 283:290 a specific consensus sequence 262:290 a specific consensus sequence by the protein O-glucosyltransferase Rumi (POGLUT1 in human) 262:351 One of the evolutionarily conserved posttranslational modifications of the Notch receptors is the addition of an O-linked glucose to epidermal growth factor-like (EGF) repeats with a specific consensus sequence by the protein O-glucosyltransferase Rumi (POGLUT1 in human). 25053479 3 49 theme Notch 701:705 arg1 analysis 678:685 an in vivo structure-function analysis 648:685 an in vivo structure-function analysis of Drosophila Notch 648:705 To demonstrate that the Notch receptor itself is the biologically relevant target of Rumi in flies, and to determine the role of the 18 Rumi target sites on Notch in regulating Notch signaling, we have performed an in vivo structure-function analysis of Drosophila Notch. 25053479 1 50 theme O-linked 194:201 arg1 glucose 203:209 an O-linked glucose 191:209 an O-linked glucose 191:209 One of the evolutionarily conserved posttranslational modifications of the Notch receptors is the addition of an O-linked glucose to epidermal growth factor-like (EGF) repeats with a specific consensus sequence by the protein O-glucosyltransferase Rumi (POGLUT1 in human). 25053479 7 51 theme signaling 1371:1379 arg1 strength 1381:1388 the Notch signaling strength 1361:1388 the Notch signaling strength 1361:1388 Gene dosage and rescue experiments in animals raised at various temperatures allowed us to dissect the contribution of O-glucosylation sites to the regulation of the Notch signaling strength. 25053479 5 52 theme Notch 842:846 arg1 insertion 859:867 random insertion 852:867 random insertion of transgenes 852:881 To avoid the potential artifacts associated with overexpression of Notch and random insertion of transgenes, we have used recombineering and site-specific integration technologies, which have been adapted for usage in Drosophila in recent years. 25053479 5 52 theme Notch 842:846 arg1 overexpression 824:837 overexpression 824:837 overexpression of Notch 824:846 To avoid the potential artifacts associated with overexpression of Notch and random insertion of transgenes, we have used recombineering and site-specific integration technologies, which have been adapted for usage in Drosophila in recent years. 25053479 1 53 theme growth 224:229 arg1 repeats 249:255 epidermal growth factor-like (EGF) repeats 214:255 epidermal growth factor-like (EGF) repeats with a specific consensus sequence by the protein O-glucosyltransferase Rumi (POGLUT1 in human) 214:351 One of the evolutionarily conserved posttranslational modifications of the Notch receptors is the addition of an O-linked glucose to epidermal growth factor-like (EGF) repeats with a specific consensus sequence by the protein O-glucosyltransferase Rumi (POGLUT1 in human). 25053479 1 54 theme modifications 135:147 arg1 One 81:83 One 81:83 One 81:83 One of the evolutionarily conserved posttranslational modifications of the Notch receptors is the addition of an O-linked glucose to epidermal growth factor-like (EGF) repeats with a specific consensus sequence by the protein O-glucosyltransferase Rumi (POGLUT1 in human). 25053479 1 54 theme modifications 135:147 arg1 modifications 135:147 the evolutionarily conserved posttranslational modifications 88:147 the evolutionarily conserved posttranslational modifications of the Notch receptors 88:170 One of the evolutionarily conserved posttranslational modifications of the Notch receptors is the addition of an O-linked glucose to epidermal growth factor-like (EGF) repeats with a specific consensus sequence by the protein O-glucosyltransferase Rumi (POGLUT1 in human). 25053479 1 54 theme modifications 135:147 arg1 addition 179:186 the addition 175:186 the addition of an O-linked glucose to epidermal growth factor-like (EGF) repeats with a specific consensus sequence by the protein O-glucosyltransferase Rumi (POGLUT1 in human) 175:351 One of the evolutionarily conserved posttranslational modifications of the Notch receptors is the addition of an O-linked glucose to epidermal growth factor-like (EGF) repeats with a specific consensus sequence by the protein O-glucosyltransferase Rumi (POGLUT1 in human). 25053479 6 55 theme O-glucose 1182:1190 arg1 sites 1192:1196 Notch O-glucose sites 1176:1196 Notch O-glucose sites 1176:1196 Using gene synthesis and site-directed mutagenesis, we generated a series of Notch genomic transgenes which harbor mutations in all or specific subsets of Notch O-glucose sites. 25053479 8 56 dep reagents 1395:1402 arg1 The 1391:1393 The 1391:1393 The 1391:1393 The reagents and methods presented here can be used to address similar questions about other posttranslational modifications of Notch or other Drosophila proteins. 25053479 7 57 theme Notch 1365:1369 arg1 strength 1381:1388 the Notch signaling strength 1361:1388 the Notch signaling strength 1361:1388 Gene dosage and rescue experiments in animals raised at various temperatures allowed us to dissect the contribution of O-glucosylation sites to the regulation of the Notch signaling strength. 25053479 8 58 theme similar 1454:1460 arg1 questions 1462:1470 similar questions 1454:1470 similar questions about other posttranslational modifications of Notch or other Drosophila proteins 1454:1552 The reagents and methods presented here can be used to address similar questions about other posttranslational modifications of Notch or other Drosophila proteins. 25053479 3 59 theme target 577:582 arg1 sites 584:588 the 18 Rumi target sites 565:588 the 18 Rumi target sites on Notch 565:597 To demonstrate that the Notch receptor itself is the biologically relevant target of Rumi in flies, and to determine the role of the 18 Rumi target sites on Notch in regulating Notch signaling, we have performed an in vivo structure-function analysis of Drosophila Notch. 25053479 1 60 theme receptors 162:170 arg1 modifications 135:147 the evolutionarily conserved posttranslational modifications 88:147 the evolutionarily conserved posttranslational modifications of the Notch receptors 88:170 One of the evolutionarily conserved posttranslational modifications of the Notch receptors is the addition of an O-linked glucose to epidermal growth factor-like (EGF) repeats with a specific consensus sequence by the protein O-glucosyltransferase Rumi (POGLUT1 in human). 25053479 7 61 theme O-glucosylation 1318:1332 arg1 sites 1334:1338 O-glucosylation sites 1318:1338 O-glucosylation sites 1318:1338 Gene dosage and rescue experiments in animals raised at various temperatures allowed us to dissect the contribution of O-glucosylation sites to the regulation of the Notch signaling strength. 25053479 6 62 from subsets 1165:1171 arg1 all 1149:1151 all 1149:1151 all 1149:1151 Using gene synthesis and site-directed mutagenesis, we generated a series of Notch genomic transgenes which harbor mutations in all or specific subsets of Notch O-glucose sites. 25053479 8 63 theme posttranslational 1484:1500 arg1 modifications 1502:1514 other posttranslational modifications 1478:1514 other posttranslational modifications of Notch or other Drosophila proteins 1478:1552 The reagents and methods presented here can be used to address similar questions about other posttranslational modifications of Notch or other Drosophila proteins. 25053479 5 64 theme integration 930:940 arg1 technologies 942:953 recombineering and site-specific integration technologies 897:953 recombineering and site-specific integration technologies 897:953 To avoid the potential artifacts associated with overexpression of Notch and random insertion of transgenes, we have used recombineering and site-specific integration technologies, which have been adapted for usage in Drosophila in recent years. 25053479 6 65 theme genomic 1104:1110 arg1 transgenes 1112:1121 Notch genomic transgenes 1098:1121 Notch genomic transgenes 1098:1121 Using gene synthesis and site-directed mutagenesis, we generated a series of Notch genomic transgenes which harbor mutations in all or specific subsets of Notch O-glucose sites. 25053479 1 66 theme epidermal 214:222 arg1 repeats 249:255 epidermal growth factor-like (EGF) repeats 214:255 epidermal growth factor-like (EGF) repeats with a specific consensus sequence by the protein O-glucosyltransferase Rumi (POGLUT1 in human) 214:351 One of the evolutionarily conserved posttranslational modifications of the Notch receptors is the addition of an O-linked glucose to epidermal growth factor-like (EGF) repeats with a specific consensus sequence by the protein O-glucosyltransferase Rumi (POGLUT1 in human). 25053479 6 67 theme site-directed 1046:1058 arg1 mutagenesis 1060:1070 site-directed mutagenesis 1046:1070 site-directed mutagenesis 1046:1070 Using gene synthesis and site-directed mutagenesis, we generated a series of Notch genomic transgenes which harbor mutations in all or specific subsets of Notch O-glucose sites. 25053479 8 68 theme Drosophila 1534:1543 arg1 proteins 1545:1552 other Drosophila proteins 1528:1552 other Drosophila proteins 1528:1552 The reagents and methods presented here can be used to address similar questions about other posttranslational modifications of Notch or other Drosophila proteins. 25053479 5 69 used used 892:895 arg2 we 884:885 we 884:885 we 884:885 To avoid the potential artifacts associated with overexpression of Notch and random insertion of transgenes, we have used recombineering and site-specific integration technologies, which have been adapted for usage in Drosophila in recent years. 25053479 0 70 theme Drosophila 31:40 arg1 Notch 42:46 Drosophila Notch 31:46 Drosophila Notch 31:46 Structure-function analysis of Drosophila Notch using genomic rescue transgenes. 25053479 3 71 dep in 651:652 arg1 vivo 654:657 vivo 654:657 vivo 654:657 To demonstrate that the Notch receptor itself is the biologically relevant target of Rumi in flies, and to determine the role of the 18 Rumi target sites on Notch in regulating Notch signaling, we have performed an in vivo structure-function analysis of Drosophila Notch. 25053479 1 72 theme conserved 107:115 arg1 modifications 135:147 the evolutionarily conserved posttranslational modifications 88:147 the evolutionarily conserved posttranslational modifications of the Notch receptors 88:170 One of the evolutionarily conserved posttranslational modifications of the Notch receptors is the addition of an O-linked glucose to epidermal growth factor-like (EGF) repeats with a specific consensus sequence by the protein O-glucosyltransferase Rumi (POGLUT1 in human). 25053479 2 73 theme signaling 425:433 arg1 loss 411:414 a temperature-sensitive loss 387:414 a temperature-sensitive loss of Notch signaling 387:433 Loss of rumi in flies results in a temperature-sensitive loss of Notch signaling. 25053479 3 74 theme Notch 613:617 arg1 signaling 619:627 Notch signaling 613:627 Notch signaling 613:627 To demonstrate that the Notch receptor itself is the biologically relevant target of Rumi in flies, and to determine the role of the 18 Rumi target sites on Notch in regulating Notch signaling, we have performed an in vivo structure-function analysis of Drosophila Notch. 25053479 1 75 theme protein 299:305 arg1 Rumi 329:332 the protein O-glucosyltransferase Rumi 295:332 the protein O-glucosyltransferase Rumi (POGLUT1 in human) 295:351 One of the evolutionarily conserved posttranslational modifications of the Notch receptors is the addition of an O-linked glucose to epidermal growth factor-like (EGF) repeats with a specific consensus sequence by the protein O-glucosyltransferase Rumi (POGLUT1 in human). 25053479 1 75 theme protein 299:305 arg1 POGLUT1 335:341 POGLUT1 335:341 POGLUT1 335:341 One of the evolutionarily conserved posttranslational modifications of the Notch receptors is the addition of an O-linked glucose to epidermal growth factor-like (EGF) repeats with a specific consensus sequence by the protein O-glucosyltransferase Rumi (POGLUT1 in human). 25053479 7 76 theme various 1255:1261 arg1 temperatures 1263:1274 various temperatures 1255:1274 various temperatures 1255:1274 Gene dosage and rescue experiments in animals raised at various temperatures allowed us to dissect the contribution of O-glucosylation sites to the regulation of the Notch signaling strength. 25053479 2 77 theme temperature-sensitive 389:409 arg1 loss 411:414 a temperature-sensitive loss 387:414 a temperature-sensitive loss of Notch signaling 387:433 Loss of rumi in flies results in a temperature-sensitive loss of Notch signaling. 25053479 0 78 theme rescue 62:67 arg1 transgenes 69:78 genomic rescue transgenes 54:78 genomic rescue transgenes 54:78 Structure-function analysis of Drosophila Notch using genomic rescue transgenes. 25053479 6 79 theme Notch 1098:1102 arg1 transgenes 1112:1121 Notch genomic transgenes 1098:1121 Notch genomic transgenes 1098:1121 Using gene synthesis and site-directed mutagenesis, we generated a series of Notch genomic transgenes which harbor mutations in all or specific subsets of Notch O-glucose sites. 25053479 4 80 theme detailed 738:745 arg1 protocol 747:754 a detailed protocol 736:754 a detailed protocol for this analysis 736:772 In this chapter, we provide a detailed protocol for this analysis. 25053479 2 81 theme rumi 362:365 arg1 Loss 354:357 Loss 354:357 Loss of rumi in flies 354:374 Loss of rumi in flies results in a temperature-sensitive loss of Notch signaling. 25053479 1 82 theme EGF 244:246 arg1 repeats 249:255 epidermal growth factor-like (EGF) repeats 214:255 epidermal growth factor-like (EGF) repeats with a specific consensus sequence by the protein O-glucosyltransferase Rumi (POGLUT1 in human) 214:351 One of the evolutionarily conserved posttranslational modifications of the Notch receptors is the addition of an O-linked glucose to epidermal growth factor-like (EGF) repeats with a specific consensus sequence by the protein O-glucosyltransferase Rumi (POGLUT1 in human). 25053479 1 83 with repeats 249:255 arg1 sequence 283:290 a specific consensus sequence 262:290 a specific consensus sequence by the protein O-glucosyltransferase Rumi (POGLUT1 in human) 262:351 One of the evolutionarily conserved posttranslational modifications of the Notch receptors is the addition of an O-linked glucose to epidermal growth factor-like (EGF) repeats with a specific consensus sequence by the protein O-glucosyltransferase Rumi (POGLUT1 in human). 25053479 7 84 theme rescue 1215:1220 arg1 experiments 1222:1232 rescue experiments 1215:1232 rescue experiments 1215:1232 Gene dosage and rescue experiments in animals raised at various temperatures allowed us to dissect the contribution of O-glucosylation sites to the regulation of the Notch signaling strength. 25053479 3 85 theme Rumi 521:524 arg1 target 511:516 the biologically relevant target 485:516 the biologically relevant target of Rumi in flies 485:533 To demonstrate that the Notch receptor itself is the biologically relevant target of Rumi in flies, and to determine the role of the 18 Rumi target sites on Notch in regulating Notch signaling, we have performed an in vivo structure-function analysis of Drosophila Notch. 25053479 3 85 theme Rumi 521:524 arg1 receptor 466:473 the Notch receptor 456:473 the Notch receptor itself 456:480 To demonstrate that the Notch receptor itself is the biologically relevant target of Rumi in flies, and to determine the role of the 18 Rumi target sites on Notch in regulating Notch signaling, we have performed an in vivo structure-function analysis of Drosophila Notch. 26121645 7 0 theme assays 1462:1467 arg1 array 1453:1457 an array 1450:1457 an array of assays, determining the envelope glycoprotein levels in mutant viral particles, their infectivity and the capture and transmission efficiencies of mutant virus particles by DC-SIGN 1450:1641 The generated HIV-1NL4.3 mutants were subjected to an array of assays, determining the envelope glycoprotein levels in mutant viral particles, their infectivity and the capture and transmission efficiencies of mutant virus particles by DC-SIGN. 26121645 10 1 theme disulphide 2088:2097 arg1 bridges 2099:2105 well-defined disulphide bridges 2075:2105 well-defined disulphide bridges of gp120 2075:2114 It was shown that the N-glycan environment around well-defined disulphide bridges of gp120 is highly critical to allow efficient viral infection and transmission. 26121645 2 2 from glycans 428:434 arg1 gp120 445:449 HIV-1 gp120 439:449 HIV-1 gp120 439:449 Using a probability calculation, we here demonstrate that there is a co-localization of disulphide bridges and N-linked glycans in HIV-1 gp120, with a predominance of N-linked glycans in close proximity to disulphide bridges, at the C-terminal side of the involved cysteines. 26121645 2 3 theme cysteines 573:581 arg1 side 552:555 the C-terminal side 537:555 the C-terminal side of the involved cysteines 537:581 Using a probability calculation, we here demonstrate that there is a co-localization of disulphide bridges and N-linked glycans in HIV-1 gp120, with a predominance of N-linked glycans in close proximity to disulphide bridges, at the C-terminal side of the involved cysteines. 26121645 3 4 theme N-terminal 680:689 arg1 side 691:694 the N-terminal side 676:694 the N-terminal side of the involved cysteines 676:720 Also, N-glycans are frequently found immediately adjacent to disulphide bridges in gp120 at the N-terminal side of the involved cysteines. 26121645 6 5 theme HIV-1 1236:1240 arg1 gp120 1242:1246 HIV-1 gp120 1236:1246 HIV-1 gp120 1236:1246 The potential functional role of the presence of N-glycans near disulphide bridges in HIV-1 gp120 was studied using site-directed mutagenesis, either by deleting conserved N-glycans or by inserting new N-glycosylation sites near disulphide bridges. 26121645 7 6 theme generated 1403:1411 arg1 mutants 1424:1430 The generated HIV-1NL4.3 mutants 1399:1430 The generated HIV-1NL4.3 mutants 1399:1430 The generated HIV-1NL4.3 mutants were subjected to an array of assays, determining the envelope glycoprotein levels in mutant viral particles, their infectivity and the capture and transmission efficiencies of mutant virus particles by DC-SIGN. 26121645 1 7 gly glycoprotein 187:198 arg1 glycoprotein 187:198 The HIV envelope glycoprotein gp120 170:204 The HIV envelope glycoprotein gp120 170:204 The HIV envelope glycoprotein gp120 contains nine disulphide bridges and is highly glycosylated, carrying on average 24 N-linked glycans. 26121645 3 8 from bridges 656:662 arg1 gp120 667:671 gp120 667:671 gp120 at the N-terminal side of the involved cysteines 667:720 Also, N-glycans are frequently found immediately adjacent to disulphide bridges in gp120 at the N-terminal side of the involved cysteines. 26121645 3 8 from bridges 656:662 arg1 side 691:694 the N-terminal side 676:694 the N-terminal side of the involved cysteines 676:720 Also, N-glycans are frequently found immediately adjacent to disulphide bridges in gp120 at the N-terminal side of the involved cysteines. 26121645 3 9 theme involved 703:710 arg1 cysteines 712:720 the involved cysteines 699:720 the involved cysteines 699:720 Also, N-glycans are frequently found immediately adjacent to disulphide bridges in gp120 at the N-terminal side of the involved cysteines. 26121645 5 10 from virus 1143:1147 arg1 E2 1101:1102 E2 1101:1102 E2 from HCV 1101:1111 Such a pronounced co-localization of disulphide bridges and N-glycans was also found for the N-glycans on glycoprotein E1 of the hepatitis C virus (HCV) but not for other heavily glycosylated proteins such as E2 from HCV and the surface GP from Ebola virus. 26121645 5 10 from virus 1143:1147 arg1 GP 1129:1130 the surface GP 1117:1130 the surface GP 1117:1130 Such a pronounced co-localization of disulphide bridges and N-glycans was also found for the N-glycans on glycoprotein E1 of the hepatitis C virus (HCV) but not for other heavily glycosylated proteins such as E2 from HCV and the surface GP from Ebola virus. 26121645 1 11 theme envelope 178:185 arg1 gp120 200:204 The HIV envelope glycoprotein gp120 170:204 The HIV envelope glycoprotein gp120 170:204 The HIV envelope glycoprotein gp120 contains nine disulphide bridges and is highly glycosylated, carrying on average 24 N-linked glycans. 26121645 4 12 theme involved 872:879 arg1 cysteines 881:889 the involved cysteines 868:889 the involved cysteines 868:889 In contrast, N-glycans at positions close to, but not immediately neighboring disulphide bridges seem to be disfavored at the N-terminal side of the involved cysteines. 26121645 2 13 theme probability 316:326 arg1 calculation 328:338 a probability calculation 314:338 a probability calculation 314:338 Using a probability calculation, we here demonstrate that there is a co-localization of disulphide bridges and N-linked glycans in HIV-1 gp120, with a predominance of N-linked glycans in close proximity to disulphide bridges, at the C-terminal side of the involved cysteines. 26121645 7 14 theme virus 1616:1620 arg1 particles 1622:1630 mutant virus particles 1609:1630 mutant virus particles 1609:1630 The generated HIV-1NL4.3 mutants were subjected to an array of assays, determining the envelope glycoprotein levels in mutant viral particles, their infectivity and the capture and transmission efficiencies of mutant virus particles by DC-SIGN. 26121645 2 15 from glycans 484:490 arg1 proximity 501:509 close proximity 495:509 close proximity to disulphide bridges 495:531 Using a probability calculation, we here demonstrate that there is a co-localization of disulphide bridges and N-linked glycans in HIV-1 gp120, with a predominance of N-linked glycans in close proximity to disulphide bridges, at the C-terminal side of the involved cysteines. 26121645 6 16 theme presence 1187:1194 arg1 role 1175:1178 The potential functional role 1150:1178 The potential functional role of the presence of N-glycans near disulphide bridges in HIV-1 gp120 1150:1246 The potential functional role of the presence of N-glycans near disulphide bridges in HIV-1 gp120 was studied using site-directed mutagenesis, either by deleting conserved N-glycans or by inserting new N-glycosylation sites near disulphide bridges. 26121645 5 17 gly glycosylated 1071:1082 arg1 proteins 1084:1091 other heavily glycosylated proteins 1057:1091 other heavily glycosylated proteins such as E2 from HCV and the surface GP from Ebola virus 1057:1147 Such a pronounced co-localization of disulphide bridges and N-glycans was also found for the N-glycans on glycoprotein E1 of the hepatitis C virus (HCV) but not for other heavily glycosylated proteins such as E2 from HCV and the surface GP from Ebola virus. 26121645 5 17 gly glycosylated 1071:1082 arg1 E2 1101:1102 E2 1101:1102 E2 from HCV 1101:1111 Such a pronounced co-localization of disulphide bridges and N-glycans was also found for the N-glycans on glycoprotein E1 of the hepatitis C virus (HCV) but not for other heavily glycosylated proteins such as E2 from HCV and the surface GP from Ebola virus. 26121645 5 17 gly glycosylated 1071:1082 arg1 GP 1129:1130 the surface GP 1117:1130 the surface GP 1117:1130 Such a pronounced co-localization of disulphide bridges and N-glycans was also found for the N-glycans on glycoprotein E1 of the hepatitis C virus (HCV) but not for other heavily glycosylated proteins such as E2 from HCV and the surface GP from Ebola virus. 26121645 3 18 from side 691:694 arg1 gp120 667:671 gp120 667:671 gp120 at the N-terminal side of the involved cysteines 667:720 Also, N-glycans are frequently found immediately adjacent to disulphide bridges in gp120 at the N-terminal side of the involved cysteines. 26121645 3 18 from side 691:694 arg1 bridges 656:662 disulphide bridges 645:662 disulphide bridges in gp120 at the N-terminal side of the involved cysteines 645:720 Also, N-glycans are frequently found immediately adjacent to disulphide bridges in gp120 at the N-terminal side of the involved cysteines. 26121645 8 19 theme several 1743:1749 arg1 preservation 1727:1738 the preservation 1723:1738 the preservation of several of these functions of gp120 1723:1777 Three N-glycans located nearby disulphide bridges were found to be crucial for the preservation of several of these functions of gp120. 26121645 4 20 theme cysteines 881:889 arg1 side 860:863 the N-terminal side 845:863 the N-terminal side of the involved cysteines 845:889 In contrast, N-glycans at positions close to, but not immediately neighboring disulphide bridges seem to be disfavored at the N-terminal side of the involved cysteines. 26121645 9 21 theme broad 1932:1936 arg1 variety 1938:1944 a broad variety 1930:1944 a broad variety of virus strains 1930:1961 In addition, introduction of new N-glycans upstream of several disulphide bridges, at locations where there was a significant absence of N-glycans in a broad variety of virus strains, was found to result in a complete loss of viral infectivity. 26121645 9 21 theme broad 1932:1936 arg1 strains 1955:1961 virus strains 1949:1961 virus strains 1949:1961 In addition, introduction of new N-glycans upstream of several disulphide bridges, at locations where there was a significant absence of N-glycans in a broad variety of virus strains, was found to result in a complete loss of viral infectivity. 26121645 0 22 theme Virus 150:154 arg1 Transmission 156:167 Virus Transmission 150:167 Virus Transmission 150:167 Several N-Glycans on the HIV Envelope Glycoprotein gp120 Preferentially Locate Near Disulphide Bridges and Are Required for Efficient Infectivity and Virus Transmission. 26121645 5 23 theme C 1031:1031 arg1 HCV 1040:1042 HCV 1040:1042 HCV 1040:1042 Such a pronounced co-localization of disulphide bridges and N-glycans was also found for the N-glycans on glycoprotein E1 of the hepatitis C virus (HCV) but not for other heavily glycosylated proteins such as E2 from HCV and the surface GP from Ebola virus. 26121645 5 23 theme C 1031:1031 arg1 virus 1033:1037 the hepatitis C virus 1017:1037 the hepatitis C virus (HCV) 1017:1043 Such a pronounced co-localization of disulphide bridges and N-glycans was also found for the N-glycans on glycoprotein E1 of the hepatitis C virus (HCV) but not for other heavily glycosylated proteins such as E2 from HCV and the surface GP from Ebola virus. 26121645 5 24 theme pronounced 899:908 arg1 co-localization 910:924 Such a pronounced co-localization 892:924 Such a pronounced co-localization of disulphide bridges 892:946 Such a pronounced co-localization of disulphide bridges and N-glycans was also found for the N-glycans on glycoprotein E1 of the hepatitis C virus (HCV) but not for other heavily glycosylated proteins such as E2 from HCV and the surface GP from Ebola virus. 26121645 7 25 theme transmission 1580:1591 arg1 efficiencies 1593:1604 transmission efficiencies 1580:1604 transmission efficiencies 1580:1604 The generated HIV-1NL4.3 mutants were subjected to an array of assays, determining the envelope glycoprotein levels in mutant viral particles, their infectivity and the capture and transmission efficiencies of mutant virus particles by DC-SIGN. 26121645 6 26 theme functional 1164:1173 arg1 role 1175:1178 The potential functional role 1150:1178 The potential functional role of the presence of N-glycans near disulphide bridges in HIV-1 gp120 1150:1246 The potential functional role of the presence of N-glycans near disulphide bridges in HIV-1 gp120 was studied using site-directed mutagenesis, either by deleting conserved N-glycans or by inserting new N-glycosylation sites near disulphide bridges. 26121645 6 27 from role 1175:1178 arg1 gp120 1242:1246 HIV-1 gp120 1236:1246 HIV-1 gp120 1236:1246 The potential functional role of the presence of N-glycans near disulphide bridges in HIV-1 gp120 was studied using site-directed mutagenesis, either by deleting conserved N-glycans or by inserting new N-glycosylation sites near disulphide bridges. 26121645 9 28 from locations 1866:1874 arg1 introduction 1793:1804 introduction 1793:1804 introduction 1793:1804 In addition, introduction of new N-glycans upstream of several disulphide bridges, at locations where there was a significant absence of N-glycans in a broad variety of virus strains, was found to result in a complete loss of viral infectivity. 26121645 9 29 theme strains 1955:1961 arg1 variety 1938:1944 a broad variety 1930:1944 a broad variety of virus strains 1930:1961 In addition, introduction of new N-glycans upstream of several disulphide bridges, at locations where there was a significant absence of N-glycans in a broad variety of virus strains, was found to result in a complete loss of viral infectivity. 26121645 9 29 theme strains 1955:1961 arg1 strains 1955:1961 virus strains 1949:1961 virus strains 1949:1961 In addition, introduction of new N-glycans upstream of several disulphide bridges, at locations where there was a significant absence of N-glycans in a broad variety of virus strains, was found to result in a complete loss of viral infectivity. 26121645 6 30 theme new 1348:1350 arg1 sites 1368:1372 new N-glycosylation sites 1348:1372 new N-glycosylation sites 1348:1372 The potential functional role of the presence of N-glycans near disulphide bridges in HIV-1 gp120 was studied using site-directed mutagenesis, either by deleting conserved N-glycans or by inserting new N-glycosylation sites near disulphide bridges. 26121645 0 31 theme Near 79:82 arg1 Bridges 95:101 Near Disulphide Bridges 79:101 Near Disulphide Bridges 79:101 Several N-Glycans on the HIV Envelope Glycoprotein gp120 Preferentially Locate Near Disulphide Bridges and Are Required for Efficient Infectivity and Virus Transmission. 26121645 9 32 theme viral 2006:2010 arg1 infectivity 2012:2022 viral infectivity 2006:2022 viral infectivity 2006:2022 In addition, introduction of new N-glycans upstream of several disulphide bridges, at locations where there was a significant absence of N-glycans in a broad variety of virus strains, was found to result in a complete loss of viral infectivity. 26121645 4 33 theme close 759:763 arg1 positions 749:757 positions 749:757 positions close to 749:766 In contrast, N-glycans at positions close to, but not immediately neighboring disulphide bridges seem to be disfavored at the N-terminal side of the involved cysteines. 26121645 5 34 theme other 1057:1061 arg1 proteins 1084:1091 other heavily glycosylated proteins 1057:1091 other heavily glycosylated proteins such as E2 from HCV and the surface GP from Ebola virus 1057:1147 Such a pronounced co-localization of disulphide bridges and N-glycans was also found for the N-glycans on glycoprotein E1 of the hepatitis C virus (HCV) but not for other heavily glycosylated proteins such as E2 from HCV and the surface GP from Ebola virus. 26121645 5 34 theme other 1057:1061 arg1 E2 1101:1102 E2 1101:1102 E2 from HCV 1101:1111 Such a pronounced co-localization of disulphide bridges and N-glycans was also found for the N-glycans on glycoprotein E1 of the hepatitis C virus (HCV) but not for other heavily glycosylated proteins such as E2 from HCV and the surface GP from Ebola virus. 26121645 5 34 theme other 1057:1061 arg1 GP 1129:1130 the surface GP 1117:1130 the surface GP 1117:1130 Such a pronounced co-localization of disulphide bridges and N-glycans was also found for the N-glycans on glycoprotein E1 of the hepatitis C virus (HCV) but not for other heavily glycosylated proteins such as E2 from HCV and the surface GP from Ebola virus. 26121645 1 35 gly glycosylated 253:264 arg1 gp120 200:204 The HIV envelope glycoprotein gp120 170:204 The HIV envelope glycoprotein gp120 170:204 The HIV envelope glycoprotein gp120 contains nine disulphide bridges and is highly glycosylated, carrying on average 24 N-linked glycans. 26121645 2 36 theme disulphide 514:523 arg1 bridges 525:531 disulphide bridges 514:531 disulphide bridges 514:531 Using a probability calculation, we here demonstrate that there is a co-localization of disulphide bridges and N-linked glycans in HIV-1 gp120, with a predominance of N-linked glycans in close proximity to disulphide bridges, at the C-terminal side of the involved cysteines. 26121645 2 37 theme bridges 407:413 arg1 co-localization 377:391 a co-localization 375:391 a co-localization of disulphide bridges and N-linked glycans in HIV-1 gp120 375:449 Using a probability calculation, we here demonstrate that there is a co-localization of disulphide bridges and N-linked glycans in HIV-1 gp120, with a predominance of N-linked glycans in close proximity to disulphide bridges, at the C-terminal side of the involved cysteines. 26121645 5 38 theme glycosylated 1071:1082 arg1 proteins 1084:1091 other heavily glycosylated proteins 1057:1091 other heavily glycosylated proteins such as E2 from HCV and the surface GP from Ebola virus 1057:1147 Such a pronounced co-localization of disulphide bridges and N-glycans was also found for the N-glycans on glycoprotein E1 of the hepatitis C virus (HCV) but not for other heavily glycosylated proteins such as E2 from HCV and the surface GP from Ebola virus. 26121645 5 38 theme glycosylated 1071:1082 arg1 E2 1101:1102 E2 1101:1102 E2 from HCV 1101:1111 Such a pronounced co-localization of disulphide bridges and N-glycans was also found for the N-glycans on glycoprotein E1 of the hepatitis C virus (HCV) but not for other heavily glycosylated proteins such as E2 from HCV and the surface GP from Ebola virus. 26121645 5 38 theme glycosylated 1071:1082 arg1 GP 1129:1130 the surface GP 1117:1130 the surface GP 1117:1130 Such a pronounced co-localization of disulphide bridges and N-glycans was also found for the N-glycans on glycoprotein E1 of the hepatitis C virus (HCV) but not for other heavily glycosylated proteins such as E2 from HCV and the surface GP from Ebola virus. 26121645 9 39 theme complete 1989:1996 arg1 loss 1998:2001 a complete loss 1987:2001 a complete loss of viral infectivity 1987:2022 In addition, introduction of new N-glycans upstream of several disulphide bridges, at locations where there was a significant absence of N-glycans in a broad variety of virus strains, was found to result in a complete loss of viral infectivity. 26121645 0 40 theme Several 0:6 arg1 N-Glycans 8:16 Several N-Glycans 0:16 Several N-Glycans on the HIV Envelope Glycoprotein gp120 0:55 Several N-Glycans on the HIV Envelope Glycoprotein gp120 Preferentially Locate Near Disulphide Bridges and Are Required for Efficient Infectivity and Virus Transmission. 26121645 5 41 theme bridges 940:946 arg1 N-glycans 952:960 N-glycans 952:960 N-glycans 952:960 Such a pronounced co-localization of disulphide bridges and N-glycans was also found for the N-glycans on glycoprotein E1 of the hepatitis C virus (HCV) but not for other heavily glycosylated proteins such as E2 from HCV and the surface GP from Ebola virus. 26121645 5 41 theme bridges 940:946 arg1 co-localization 910:924 Such a pronounced co-localization 892:924 Such a pronounced co-localization of disulphide bridges 892:946 Such a pronounced co-localization of disulphide bridges and N-glycans was also found for the N-glycans on glycoprotein E1 of the hepatitis C virus (HCV) but not for other heavily glycosylated proteins such as E2 from HCV and the surface GP from Ebola virus. 26121645 10 42 theme viral 2154:2158 arg1 infection 2160:2168 efficient viral infection 2144:2168 efficient viral infection 2144:2168 It was shown that the N-glycan environment around well-defined disulphide bridges of gp120 is highly critical to allow efficient viral infection and transmission. 26121645 5 43 theme Ebola 1137:1141 arg1 virus 1143:1147 Ebola virus 1137:1147 Ebola virus 1137:1147 Such a pronounced co-localization of disulphide bridges and N-glycans was also found for the N-glycans on glycoprotein E1 of the hepatitis C virus (HCV) but not for other heavily glycosylated proteins such as E2 from HCV and the surface GP from Ebola virus. 26121645 2 44 theme N-linked 475:482 arg1 glycans 484:490 N-linked glycans 475:490 N-linked glycans in close proximity to disulphide bridges 475:531 Using a probability calculation, we here demonstrate that there is a co-localization of disulphide bridges and N-linked glycans in HIV-1 gp120, with a predominance of N-linked glycans in close proximity to disulphide bridges, at the C-terminal side of the involved cysteines. 26121645 9 45 theme infectivity 2012:2022 arg1 loss 1998:2001 a complete loss 1987:2001 a complete loss of viral infectivity 1987:2022 In addition, introduction of new N-glycans upstream of several disulphide bridges, at locations where there was a significant absence of N-glycans in a broad variety of virus strains, was found to result in a complete loss of viral infectivity. 26121645 2 46 theme N-linked 419:426 arg1 glycans 428:434 N-linked glycans 419:434 N-linked glycans 419:434 Using a probability calculation, we here demonstrate that there is a co-localization of disulphide bridges and N-linked glycans in HIV-1 gp120, with a predominance of N-linked glycans in close proximity to disulphide bridges, at the C-terminal side of the involved cysteines. 26121645 6 47 theme disulphide 1379:1388 arg1 bridges 1390:1396 disulphide bridges 1379:1396 disulphide bridges 1379:1396 The potential functional role of the presence of N-glycans near disulphide bridges in HIV-1 gp120 was studied using site-directed mutagenesis, either by deleting conserved N-glycans or by inserting new N-glycosylation sites near disulphide bridges. 26121645 0 48 theme HIV 25:27 arg1 gp120 51:55 the HIV Envelope Glycoprotein gp120 21:55 the HIV Envelope Glycoprotein gp120 21:55 Several N-Glycans on the HIV Envelope Glycoprotein gp120 Preferentially Locate Near Disulphide Bridges and Are Required for Efficient Infectivity and Virus Transmission. 26121645 7 49 theme glycoprotein 1495:1506 arg1 levels 1508:1513 the envelope glycoprotein levels 1482:1513 the envelope glycoprotein levels in mutant viral particles 1482:1539 The generated HIV-1NL4.3 mutants were subjected to an array of assays, determining the envelope glycoprotein levels in mutant viral particles, their infectivity and the capture and transmission efficiencies of mutant virus particles by DC-SIGN. 26121645 5 50 gly glycoprotein 998:1009 arg1 glycoprotein 998:1009 glycoprotein E1 998:1012 glycoprotein E1 of the hepatitis C virus (HCV) 998:1043 Such a pronounced co-localization of disulphide bridges and N-glycans was also found for the N-glycans on glycoprotein E1 of the hepatitis C virus (HCV) but not for other heavily glycosylated proteins such as E2 from HCV and the surface GP from Ebola virus. 26121645 0 51 theme Glycoprotein 38:49 arg1 gp120 51:55 the HIV Envelope Glycoprotein gp120 21:55 the HIV Envelope Glycoprotein gp120 21:55 Several N-Glycans on the HIV Envelope Glycoprotein gp120 Preferentially Locate Near Disulphide Bridges and Are Required for Efficient Infectivity and Virus Transmission. 26121645 5 52 theme hepatitis 1021:1029 arg1 HCV 1040:1042 HCV 1040:1042 HCV 1040:1042 Such a pronounced co-localization of disulphide bridges and N-glycans was also found for the N-glycans on glycoprotein E1 of the hepatitis C virus (HCV) but not for other heavily glycosylated proteins such as E2 from HCV and the surface GP from Ebola virus. 26121645 5 52 theme hepatitis 1021:1029 arg1 virus 1033:1037 the hepatitis C virus 1017:1037 the hepatitis C virus (HCV) 1017:1043 Such a pronounced co-localization of disulphide bridges and N-glycans was also found for the N-glycans on glycoprotein E1 of the hepatitis C virus (HCV) but not for other heavily glycosylated proteins such as E2 from HCV and the surface GP from Ebola virus. 26121645 2 53 from bridges 407:413 arg1 gp120 445:449 HIV-1 gp120 439:449 HIV-1 gp120 439:449 Using a probability calculation, we here demonstrate that there is a co-localization of disulphide bridges and N-linked glycans in HIV-1 gp120, with a predominance of N-linked glycans in close proximity to disulphide bridges, at the C-terminal side of the involved cysteines. 26121645 7 54 from capture 1568:1574 arg1 particles 1531:1539 mutant viral particles 1518:1539 mutant viral particles 1518:1539 The generated HIV-1NL4.3 mutants were subjected to an array of assays, determining the envelope glycoprotein levels in mutant viral particles, their infectivity and the capture and transmission efficiencies of mutant virus particles by DC-SIGN. 26121645 6 55 gly N-glycosylation 1352:1366 arg2 sites 1368:1372 new N-glycosylation sites 1348:1372 new N-glycosylation sites 1348:1372 The potential functional role of the presence of N-glycans near disulphide bridges in HIV-1 gp120 was studied using site-directed mutagenesis, either by deleting conserved N-glycans or by inserting new N-glycosylation sites near disulphide bridges. 26121645 9 56 theme disulphide 1843:1852 arg1 bridges 1854:1860 several disulphide bridges 1835:1860 several disulphide bridges 1835:1860 In addition, introduction of new N-glycans upstream of several disulphide bridges, at locations where there was a significant absence of N-glycans in a broad variety of virus strains, was found to result in a complete loss of viral infectivity. 26121645 1 57 contain contains 206:213 arg2 bridges 231:237 nine disulphide bridges 215:237 nine disulphide bridges 215:237 The HIV envelope glycoprotein gp120 contains nine disulphide bridges and is highly glycosylated, carrying on average 24 N-linked glycans. 26121645 1 57 contain contains 206:213 arg1 gp120 200:204 The HIV envelope glycoprotein gp120 170:204 The HIV envelope glycoprotein gp120 170:204 The HIV envelope glycoprotein gp120 contains nine disulphide bridges and is highly glycosylated, carrying on average 24 N-linked glycans. 26121645 4 58 theme neighboring 789:799 arg1 bridges 812:818 N-glycans at positions close to, but not immediately neighboring disulphide bridges 736:818 N-glycans at positions close to, but not immediately neighboring disulphide bridges 736:818 In contrast, N-glycans at positions close to, but not immediately neighboring disulphide bridges seem to be disfavored at the N-terminal side of the involved cysteines. 26121645 9 59 theme N-glycans 1813:1821 arg1 introduction 1793:1804 introduction 1793:1804 introduction 1793:1804 In addition, introduction of new N-glycans upstream of several disulphide bridges, at locations where there was a significant absence of N-glycans in a broad variety of virus strains, was found to result in a complete loss of viral infectivity. 26121645 5 60 theme glycoprotein 998:1009 arg1 E1 1011:1012 glycoprotein E1 998:1012 glycoprotein E1 of the hepatitis C virus (HCV) 998:1043 Such a pronounced co-localization of disulphide bridges and N-glycans was also found for the N-glycans on glycoprotein E1 of the hepatitis C virus (HCV) but not for other heavily glycosylated proteins such as E2 from HCV and the surface GP from Ebola virus. 26121645 1 61 link N-linked 290:297 arg1 glycans 299:305 24 N-linked glycans 287:305 24 N-linked glycans 287:305 The HIV envelope glycoprotein gp120 contains nine disulphide bridges and is highly glycosylated, carrying on average 24 N-linked glycans. 26121645 4 62 theme N-terminal 849:858 arg1 side 860:863 the N-terminal side 845:863 the N-terminal side of the involved cysteines 845:889 In contrast, N-glycans at positions close to, but not immediately neighboring disulphide bridges seem to be disfavored at the N-terminal side of the involved cysteines. 26121645 5 63 from HCV 1109:1111 arg1 E2 1101:1102 E2 1101:1102 E2 from HCV 1101:1111 Such a pronounced co-localization of disulphide bridges and N-glycans was also found for the N-glycans on glycoprotein E1 of the hepatitis C virus (HCV) but not for other heavily glycosylated proteins such as E2 from HCV and the surface GP from Ebola virus. 26121645 5 63 from HCV 1109:1111 arg1 GP 1129:1130 the surface GP 1117:1130 the surface GP 1117:1130 Such a pronounced co-localization of disulphide bridges and N-glycans was also found for the N-glycans on glycoprotein E1 of the hepatitis C virus (HCV) but not for other heavily glycosylated proteins such as E2 from HCV and the surface GP from Ebola virus. 26121645 8 64 theme disulphide 1675:1684 arg1 bridges 1686:1692 Three N-glycans located nearby disulphide bridges 1644:1692 Three N-glycans located nearby disulphide bridges 1644:1692 Three N-glycans located nearby disulphide bridges were found to be crucial for the preservation of several of these functions of gp120. 26121645 7 65 from levels 1508:1513 arg1 particles 1531:1539 mutant viral particles 1518:1539 mutant viral particles 1518:1539 The generated HIV-1NL4.3 mutants were subjected to an array of assays, determining the envelope glycoprotein levels in mutant viral particles, their infectivity and the capture and transmission efficiencies of mutant virus particles by DC-SIGN. 26121645 7 66 theme HIV-1NL4.3 1413:1422 arg1 mutants 1424:1430 The generated HIV-1NL4.3 mutants 1399:1430 The generated HIV-1NL4.3 mutants 1399:1430 The generated HIV-1NL4.3 mutants were subjected to an array of assays, determining the envelope glycoprotein levels in mutant viral particles, their infectivity and the capture and transmission efficiencies of mutant virus particles by DC-SIGN. 26121645 10 67 theme well-defined 2075:2086 arg1 bridges 2099:2105 well-defined disulphide bridges 2075:2105 well-defined disulphide bridges of gp120 2075:2114 It was shown that the N-glycan environment around well-defined disulphide bridges of gp120 is highly critical to allow efficient viral infection and transmission. 26121645 9 68 theme significant 1894:1904 arg1 absence 1906:1912 a significant absence 1892:1912 a significant absence of N-glycans 1892:1925 In addition, introduction of new N-glycans upstream of several disulphide bridges, at locations where there was a significant absence of N-glycans in a broad variety of virus strains, was found to result in a complete loss of viral infectivity. 26121645 6 69 theme disulphide 1214:1223 arg1 bridges 1225:1231 disulphide bridges 1214:1231 disulphide bridges 1214:1231 The potential functional role of the presence of N-glycans near disulphide bridges in HIV-1 gp120 was studied using site-directed mutagenesis, either by deleting conserved N-glycans or by inserting new N-glycosylation sites near disulphide bridges. 26121645 1 70 theme HIV 174:176 arg1 gp120 200:204 The HIV envelope glycoprotein gp120 170:204 The HIV envelope glycoprotein gp120 170:204 The HIV envelope glycoprotein gp120 contains nine disulphide bridges and is highly glycosylated, carrying on average 24 N-linked glycans. 26121645 3 71 theme cysteines 712:720 arg1 side 691:694 the N-terminal side 676:694 the N-terminal side of the involved cysteines 676:720 Also, N-glycans are frequently found immediately adjacent to disulphide bridges in gp120 at the N-terminal side of the involved cysteines. 26121645 6 72 theme N-glycans 1199:1207 arg1 presence 1187:1194 the presence 1183:1194 the presence of N-glycans near disulphide bridges 1183:1231 The potential functional role of the presence of N-glycans near disulphide bridges in HIV-1 gp120 was studied using site-directed mutagenesis, either by deleting conserved N-glycans or by inserting new N-glycosylation sites near disulphide bridges. 26121645 5 73 from N-glycans 985:993 arg1 E1 1011:1012 glycoprotein E1 998:1012 glycoprotein E1 of the hepatitis C virus (HCV) 998:1043 Such a pronounced co-localization of disulphide bridges and N-glycans was also found for the N-glycans on glycoprotein E1 of the hepatitis C virus (HCV) but not for other heavily glycosylated proteins such as E2 from HCV and the surface GP from Ebola virus. 26121645 1 74 theme glycoprotein 187:198 arg1 gp120 200:204 The HIV envelope glycoprotein gp120 170:204 The HIV envelope glycoprotein gp120 170:204 The HIV envelope glycoprotein gp120 contains nine disulphide bridges and is highly glycosylated, carrying on average 24 N-linked glycans. 26121645 7 75 theme particles 1622:1630 arg1 efficiencies 1593:1604 transmission efficiencies 1580:1604 transmission efficiencies 1580:1604 The generated HIV-1NL4.3 mutants were subjected to an array of assays, determining the envelope glycoprotein levels in mutant viral particles, their infectivity and the capture and transmission efficiencies of mutant virus particles by DC-SIGN. 26121645 7 75 theme particles 1622:1630 arg1 levels 1508:1513 the envelope glycoprotein levels 1482:1513 the envelope glycoprotein levels in mutant viral particles 1482:1539 The generated HIV-1NL4.3 mutants were subjected to an array of assays, determining the envelope glycoprotein levels in mutant viral particles, their infectivity and the capture and transmission efficiencies of mutant virus particles by DC-SIGN. 26121645 7 75 theme particles 1622:1630 arg1 infectivity 1548:1558 their infectivity 1542:1558 their infectivity 1542:1558 The generated HIV-1NL4.3 mutants were subjected to an array of assays, determining the envelope glycoprotein levels in mutant viral particles, their infectivity and the capture and transmission efficiencies of mutant virus particles by DC-SIGN. 26121645 7 75 theme particles 1622:1630 arg1 capture 1568:1574 capture 1568:1574 capture 1568:1574 The generated HIV-1NL4.3 mutants were subjected to an array of assays, determining the envelope glycoprotein levels in mutant viral particles, their infectivity and the capture and transmission efficiencies of mutant virus particles by DC-SIGN. 26121645 10 76 theme gp120 2110:2114 arg1 bridges 2099:2105 well-defined disulphide bridges 2075:2105 well-defined disulphide bridges of gp120 2075:2114 It was shown that the N-glycan environment around well-defined disulphide bridges of gp120 is highly critical to allow efficient viral infection and transmission. 26121645 0 77 theme Efficient 124:132 arg1 Infectivity 134:144 Efficient Infectivity 124:144 Efficient Infectivity 124:144 Several N-Glycans on the HIV Envelope Glycoprotein gp120 Preferentially Locate Near Disulphide Bridges and Are Required for Efficient Infectivity and Virus Transmission. 26121645 6 78 dep using 1260:1264 arg1 inserting 1338:1346 inserting 1338:1346 inserting new N-glycosylation sites near disulphide bridges 1338:1396 The potential functional role of the presence of N-glycans near disulphide bridges in HIV-1 gp120 was studied using site-directed mutagenesis, either by deleting conserved N-glycans or by inserting new N-glycosylation sites near disulphide bridges. 26121645 6 78 dep using 1260:1264 arg1 deleting 1303:1310 deleting 1303:1310 deleting conserved N-glycans 1303:1330 The potential functional role of the presence of N-glycans near disulphide bridges in HIV-1 gp120 was studied using site-directed mutagenesis, either by deleting conserved N-glycans or by inserting new N-glycosylation sites near disulphide bridges. 26121645 7 79 theme mutant 1609:1614 arg1 particles 1622:1630 mutant virus particles 1609:1630 mutant virus particles 1609:1630 The generated HIV-1NL4.3 mutants were subjected to an array of assays, determining the envelope glycoprotein levels in mutant viral particles, their infectivity and the capture and transmission efficiencies of mutant virus particles by DC-SIGN. 26121645 2 80 theme C-terminal 541:550 arg1 side 552:555 the C-terminal side 537:555 the C-terminal side of the involved cysteines 537:581 Using a probability calculation, we here demonstrate that there is a co-localization of disulphide bridges and N-linked glycans in HIV-1 gp120, with a predominance of N-linked glycans in close proximity to disulphide bridges, at the C-terminal side of the involved cysteines. 26121645 9 81 theme N-glycans 1917:1925 arg1 absence 1906:1912 a significant absence 1892:1912 a significant absence of N-glycans 1892:1925 In addition, introduction of new N-glycans upstream of several disulphide bridges, at locations where there was a significant absence of N-glycans in a broad variety of virus strains, was found to result in a complete loss of viral infectivity. 26121645 1 82 theme disulphide 220:229 arg1 bridges 231:237 nine disulphide bridges 215:237 nine disulphide bridges 215:237 The HIV envelope glycoprotein gp120 contains nine disulphide bridges and is highly glycosylated, carrying on average 24 N-linked glycans. 26121645 2 83 from proximity 501:509 arg1 predominance 459:470 a predominance 457:470 a predominance of N-linked glycans in close proximity to disulphide bridges 457:531 Using a probability calculation, we here demonstrate that there is a co-localization of disulphide bridges and N-linked glycans in HIV-1 gp120, with a predominance of N-linked glycans in close proximity to disulphide bridges, at the C-terminal side of the involved cysteines. 26121645 6 84 theme site-directed 1266:1278 arg1 mutagenesis 1280:1290 site-directed mutagenesis 1266:1290 site-directed mutagenesis 1266:1290 The potential functional role of the presence of N-glycans near disulphide bridges in HIV-1 gp120 was studied using site-directed mutagenesis, either by deleting conserved N-glycans or by inserting new N-glycosylation sites near disulphide bridges. 26121645 7 85 dep capture 1568:1574 arg1 the 1564:1566 the 1564:1566 the 1564:1566 The generated HIV-1NL4.3 mutants were subjected to an array of assays, determining the envelope glycoprotein levels in mutant viral particles, their infectivity and the capture and transmission efficiencies of mutant virus particles by DC-SIGN. 26121645 2 86 theme involved 564:571 arg1 cysteines 573:581 the involved cysteines 560:581 the involved cysteines 560:581 Using a probability calculation, we here demonstrate that there is a co-localization of disulphide bridges and N-linked glycans in HIV-1 gp120, with a predominance of N-linked glycans in close proximity to disulphide bridges, at the C-terminal side of the involved cysteines. 26121645 5 87 theme virus 1033:1037 arg1 E1 1011:1012 glycoprotein E1 998:1012 glycoprotein E1 of the hepatitis C virus (HCV) 998:1043 Such a pronounced co-localization of disulphide bridges and N-glycans was also found for the N-glycans on glycoprotein E1 of the hepatitis C virus (HCV) but not for other heavily glycosylated proteins such as E2 from HCV and the surface GP from Ebola virus. 26121645 6 88 theme potential 1154:1162 arg1 role 1175:1178 The potential functional role 1150:1178 The potential functional role of the presence of N-glycans near disulphide bridges in HIV-1 gp120 1150:1246 The potential functional role of the presence of N-glycans near disulphide bridges in HIV-1 gp120 was studied using site-directed mutagenesis, either by deleting conserved N-glycans or by inserting new N-glycosylation sites near disulphide bridges. 26121645 9 89 theme virus 1949:1953 arg1 strains 1955:1961 virus strains 1949:1961 virus strains 1949:1961 In addition, introduction of new N-glycans upstream of several disulphide bridges, at locations where there was a significant absence of N-glycans in a broad variety of virus strains, was found to result in a complete loss of viral infectivity. 26121645 6 90 theme N-glycosylation 1352:1366 arg1 sites 1368:1372 new N-glycosylation sites 1348:1372 new N-glycosylation sites 1348:1372 The potential functional role of the presence of N-glycans near disulphide bridges in HIV-1 gp120 was studied using site-directed mutagenesis, either by deleting conserved N-glycans or by inserting new N-glycosylation sites near disulphide bridges. 26121645 8 91 theme functions 1760:1768 arg1 several 1743:1749 several 1743:1749 several 1743:1749 Three N-glycans located nearby disulphide bridges were found to be crucial for the preservation of several of these functions of gp120. 26121645 2 92 theme close 495:499 arg1 proximity 501:509 close proximity 495:509 close proximity to disulphide bridges 495:531 Using a probability calculation, we here demonstrate that there is a co-localization of disulphide bridges and N-linked glycans in HIV-1 gp120, with a predominance of N-linked glycans in close proximity to disulphide bridges, at the C-terminal side of the involved cysteines. 26121645 2 93 from gp120 445:449 arg1 co-localization 377:391 a co-localization 375:391 a co-localization of disulphide bridges and N-linked glycans in HIV-1 gp120 375:449 Using a probability calculation, we here demonstrate that there is a co-localization of disulphide bridges and N-linked glycans in HIV-1 gp120, with a predominance of N-linked glycans in close proximity to disulphide bridges, at the C-terminal side of the involved cysteines. 26121645 10 94 theme efficient 2144:2152 arg1 infection 2160:2168 efficient viral infection 2144:2168 efficient viral infection 2144:2168 It was shown that the N-glycan environment around well-defined disulphide bridges of gp120 is highly critical to allow efficient viral infection and transmission. 26121645 0 95 theme Disulphide 84:93 arg1 Bridges 95:101 Near Disulphide Bridges 79:101 Near Disulphide Bridges 79:101 Several N-Glycans on the HIV Envelope Glycoprotein gp120 Preferentially Locate Near Disulphide Bridges and Are Required for Efficient Infectivity and Virus Transmission. 26121645 8 96 theme gp120 1773:1777 arg1 functions 1760:1768 these functions 1754:1768 these functions of gp120 1754:1777 Three N-glycans located nearby disulphide bridges were found to be crucial for the preservation of several of these functions of gp120. 26121645 2 97 theme glycans 484:490 arg1 predominance 459:470 a predominance 457:470 a predominance of N-linked glycans in close proximity to disulphide bridges 457:531 Using a probability calculation, we here demonstrate that there is a co-localization of disulphide bridges and N-linked glycans in HIV-1 gp120, with a predominance of N-linked glycans in close proximity to disulphide bridges, at the C-terminal side of the involved cysteines. 26121645 0 98 from N-Glycans 8:16 arg1 gp120 51:55 the HIV Envelope Glycoprotein gp120 21:55 the HIV Envelope Glycoprotein gp120 21:55 Several N-Glycans on the HIV Envelope Glycoprotein gp120 Preferentially Locate Near Disulphide Bridges and Are Required for Efficient Infectivity and Virus Transmission. 26121645 7 99 from efficiencies 1593:1604 arg1 particles 1531:1539 mutant viral particles 1518:1539 mutant viral particles 1518:1539 The generated HIV-1NL4.3 mutants were subjected to an array of assays, determining the envelope glycoprotein levels in mutant viral particles, their infectivity and the capture and transmission efficiencies of mutant virus particles by DC-SIGN. 26121645 7 100 gly glycoprotein 1495:1506 arg1 glycoprotein 1495:1506 envelope glycoprotein 1486:1506 the envelope glycoprotein levels in mutant viral particles 1482:1539 The generated HIV-1NL4.3 mutants were subjected to an array of assays, determining the envelope glycoprotein levels in mutant viral particles, their infectivity and the capture and transmission efficiencies of mutant virus particles by DC-SIGN. 26121645 7 101 theme viral 1525:1529 arg1 particles 1531:1539 mutant viral particles 1518:1539 mutant viral particles 1518:1539 The generated HIV-1NL4.3 mutants were subjected to an array of assays, determining the envelope glycoprotein levels in mutant viral particles, their infectivity and the capture and transmission efficiencies of mutant virus particles by DC-SIGN. 26121645 2 102 from predominance 459:470 arg1 proximity 501:509 close proximity 495:509 close proximity to disulphide bridges 495:531 Using a probability calculation, we here demonstrate that there is a co-localization of disulphide bridges and N-linked glycans in HIV-1 gp120, with a predominance of N-linked glycans in close proximity to disulphide bridges, at the C-terminal side of the involved cysteines. 26121645 10 103 theme N-glycan 2047:2054 arg1 critical 2126:2133 critical 2126:2133 critical 2126:2133 It was shown that the N-glycan environment around well-defined disulphide bridges of gp120 is highly critical to allow efficient viral infection and transmission. 26121645 10 103 theme N-glycan 2047:2054 arg1 environment 2056:2066 the N-glycan environment 2043:2066 the N-glycan environment around well-defined disulphide bridges of gp120 2043:2114 It was shown that the N-glycan environment around well-defined disulphide bridges of gp120 is highly critical to allow efficient viral infection and transmission. 26121645 6 104 theme conserved 1312:1320 arg1 N-glycans 1322:1330 conserved N-glycans 1312:1330 conserved N-glycans 1312:1330 The potential functional role of the presence of N-glycans near disulphide bridges in HIV-1 gp120 was studied using site-directed mutagenesis, either by deleting conserved N-glycans or by inserting new N-glycosylation sites near disulphide bridges. 26121645 4 105 from positions 749:757 arg1 N-glycans 736:744 N-glycans 736:744 N-glycans 736:744 In contrast, N-glycans at positions close to, but not immediately neighboring disulphide bridges seem to be disfavored at the N-terminal side of the involved cysteines. 26121645 2 106 theme disulphide 396:405 arg1 bridges 407:413 disulphide bridges 396:413 disulphide bridges 396:413 Using a probability calculation, we here demonstrate that there is a co-localization of disulphide bridges and N-linked glycans in HIV-1 gp120, with a predominance of N-linked glycans in close proximity to disulphide bridges, at the C-terminal side of the involved cysteines. 26121645 5 107 theme disulphide 929:938 arg1 bridges 940:946 disulphide bridges 929:946 disulphide bridges 929:946 Such a pronounced co-localization of disulphide bridges and N-glycans was also found for the N-glycans on glycoprotein E1 of the hepatitis C virus (HCV) but not for other heavily glycosylated proteins such as E2 from HCV and the surface GP from Ebola virus. 26121645 2 108 link N-linked 475:482 arg1 glycans 484:490 N-linked glycans 475:490 N-linked glycans in close proximity to disulphide bridges 475:531 Using a probability calculation, we here demonstrate that there is a co-localization of disulphide bridges and N-linked glycans in HIV-1 gp120, with a predominance of N-linked glycans in close proximity to disulphide bridges, at the C-terminal side of the involved cysteines. 26121645 1 109 theme N-linked 290:297 arg1 glycans 299:305 24 N-linked glycans 287:305 24 N-linked glycans 287:305 The HIV envelope glycoprotein gp120 contains nine disulphide bridges and is highly glycosylated, carrying on average 24 N-linked glycans. 26121645 2 110 theme HIV-1 439:443 arg1 gp120 445:449 HIV-1 gp120 439:449 HIV-1 gp120 439:449 Using a probability calculation, we here demonstrate that there is a co-localization of disulphide bridges and N-linked glycans in HIV-1 gp120, with a predominance of N-linked glycans in close proximity to disulphide bridges, at the C-terminal side of the involved cysteines. 26121645 3 111 theme disulphide 645:654 arg1 bridges 656:662 disulphide bridges 645:662 disulphide bridges in gp120 at the N-terminal side of the involved cysteines 645:720 Also, N-glycans are frequently found immediately adjacent to disulphide bridges in gp120 at the N-terminal side of the involved cysteines. 26121645 4 112 theme N-glycans 736:744 arg1 bridges 812:818 N-glycans at positions close to, but not immediately neighboring disulphide bridges 736:818 N-glycans at positions close to, but not immediately neighboring disulphide bridges 736:818 In contrast, N-glycans at positions close to, but not immediately neighboring disulphide bridges seem to be disfavored at the N-terminal side of the involved cysteines. 26121645 2 113 theme glycans 428:434 arg1 co-localization 377:391 a co-localization 375:391 a co-localization of disulphide bridges and N-linked glycans in HIV-1 gp120 375:449 Using a probability calculation, we here demonstrate that there is a co-localization of disulphide bridges and N-linked glycans in HIV-1 gp120, with a predominance of N-linked glycans in close proximity to disulphide bridges, at the C-terminal side of the involved cysteines. 26121645 0 114 theme Envelope 29:36 arg1 gp120 51:55 the HIV Envelope Glycoprotein gp120 21:55 the HIV Envelope Glycoprotein gp120 21:55 Several N-Glycans on the HIV Envelope Glycoprotein gp120 Preferentially Locate Near Disulphide Bridges and Are Required for Efficient Infectivity and Virus Transmission. 26121645 7 115 dep assays 1462:1467 arg1 determining 1470:1480 determining 1470:1480 determining the envelope glycoprotein levels in mutant viral particles, their infectivity and the capture and transmission efficiencies of mutant virus particles by DC-SIGN 1470:1641 The generated HIV-1NL4.3 mutants were subjected to an array of assays, determining the envelope glycoprotein levels in mutant viral particles, their infectivity and the capture and transmission efficiencies of mutant virus particles by DC-SIGN. 26121645 7 116 theme mutant 1518:1523 arg1 particles 1531:1539 mutant viral particles 1518:1539 mutant viral particles 1518:1539 The generated HIV-1NL4.3 mutants were subjected to an array of assays, determining the envelope glycoprotein levels in mutant viral particles, their infectivity and the capture and transmission efficiencies of mutant virus particles by DC-SIGN. 26121645 9 117 theme new 1809:1811 arg1 N-glycans 1813:1821 new N-glycans 1809:1821 new N-glycans 1809:1821 In addition, introduction of new N-glycans upstream of several disulphide bridges, at locations where there was a significant absence of N-glycans in a broad variety of virus strains, was found to result in a complete loss of viral infectivity. 26121645 4 118 theme disulphide 801:810 arg1 bridges 812:818 N-glycans at positions close to, but not immediately neighboring disulphide bridges 736:818 N-glycans at positions close to, but not immediately neighboring disulphide bridges 736:818 In contrast, N-glycans at positions close to, but not immediately neighboring disulphide bridges seem to be disfavored at the N-terminal side of the involved cysteines. 26121645 7 119 from infectivity 1548:1558 arg1 particles 1531:1539 mutant viral particles 1518:1539 mutant viral particles 1518:1539 The generated HIV-1NL4.3 mutants were subjected to an array of assays, determining the envelope glycoprotein levels in mutant viral particles, their infectivity and the capture and transmission efficiencies of mutant virus particles by DC-SIGN. 26121645 2 120 from co-localization 377:391 arg1 gp120 445:449 HIV-1 gp120 439:449 HIV-1 gp120 439:449 Using a probability calculation, we here demonstrate that there is a co-localization of disulphide bridges and N-linked glycans in HIV-1 gp120, with a predominance of N-linked glycans in close proximity to disulphide bridges, at the C-terminal side of the involved cysteines. 26121645 2 121 link N-linked 419:426 arg1 glycans 428:434 N-linked glycans 419:434 N-linked glycans 419:434 Using a probability calculation, we here demonstrate that there is a co-localization of disulphide bridges and N-linked glycans in HIV-1 gp120, with a predominance of N-linked glycans in close proximity to disulphide bridges, at the C-terminal side of the involved cysteines. 26121645 5 122 theme surface 1121:1127 arg1 GP 1129:1130 the surface GP 1117:1130 the surface GP 1117:1130 Such a pronounced co-localization of disulphide bridges and N-glycans was also found for the N-glycans on glycoprotein E1 of the hepatitis C virus (HCV) but not for other heavily glycosylated proteins such as E2 from HCV and the surface GP from Ebola virus. 26121645 7 123 theme envelope 1486:1493 arg1 glycoprotein 1495:1506 envelope glycoprotein 1486:1506 the envelope glycoprotein levels in mutant viral particles 1482:1539 The generated HIV-1NL4.3 mutants were subjected to an array of assays, determining the envelope glycoprotein levels in mutant viral particles, their infectivity and the capture and transmission efficiencies of mutant virus particles by DC-SIGN. 26121645 9 124 theme several 1835:1841 arg1 bridges 1854:1860 several disulphide bridges 1835:1860 several disulphide bridges 1835:1860 In addition, introduction of new N-glycans upstream of several disulphide bridges, at locations where there was a significant absence of N-glycans in a broad variety of virus strains, was found to result in a complete loss of viral infectivity. 26121645 9 125 located found 1968:1972 arg2 introduction 1793:1804 introduction 1793:1804 introduction 1793:1804 In addition, introduction of new N-glycans upstream of several disulphide bridges, at locations where there was a significant absence of N-glycans in a broad variety of virus strains, was found to result in a complete loss of viral infectivity. 26121645 9 125 located found 1968:1972 arg1 addition 1783:1790 addition 1783:1790 addition 1783:1790 In addition, introduction of new N-glycans upstream of several disulphide bridges, at locations where there was a significant absence of N-glycans in a broad variety of virus strains, was found to result in a complete loss of viral infectivity. 26121645 9 126 theme bridges 1854:1860 arg1 introduction 1793:1804 introduction 1793:1804 introduction 1793:1804 In addition, introduction of new N-glycans upstream of several disulphide bridges, at locations where there was a significant absence of N-glycans in a broad variety of virus strains, was found to result in a complete loss of viral infectivity. 26121645 8 127 theme nearby 1668:1673 arg1 bridges 1686:1692 Three N-glycans located nearby disulphide bridges 1644:1692 Three N-glycans located nearby disulphide bridges 1644:1692 Three N-glycans located nearby disulphide bridges were found to be crucial for the preservation of several of these functions of gp120. 28401776 7 0 from envelope 1387:1394 arg1 frequency 1362:1370 the frequency 1358:1370 the frequency of PNGS in the envelope of the viruses obtained from very recently infected individuals in our population 1358:1476 In brief, our observations suggest that differences in the length of the variable regions and variation in the frequency of PNGS in the envelope of the viruses obtained from very recently infected individuals in our population could be important characteristics of the unique quasispecies that is responsible for the spread of HIV in the early stages of infection in MTCT. 28401776 7 1 theme PNGS 1375:1378 arg1 frequency 1362:1370 the frequency 1358:1370 the frequency of PNGS in the envelope of the viruses obtained from very recently infected individuals in our population 1358:1476 In brief, our observations suggest that differences in the length of the variable regions and variation in the frequency of PNGS in the envelope of the viruses obtained from very recently infected individuals in our population could be important characteristics of the unique quasispecies that is responsible for the spread of HIV in the early stages of infection in MTCT. 28401776 4 2 theme region 826:831 arg1 length 807:812 length 807:812 length of the V1V2 region of the envelope sequences 807:857 Detailed analysis revealed unique features of potential N-linked glycosylation sites (PNGS) and their frequency of occurrence that built on the difference in length of the V1V2 region of the envelope sequences. 28401776 6 3 theme variant 1177:1183 arg1 interaction 1146:1156 the established interaction 1130:1156 the established interaction of the transmitted variant with the integrin α4β7 receptor and R5 co-receptor, respectively 1130:1248 Further, a stable net charge was observed in the V2 and V3 regions prompting us to speculate on the established interaction of the transmitted variant with the integrin α4β7 receptor and R5 co-receptor, respectively. 28401776 0 4 with Infants 87:93 arg1 Infection 104:112 HIV Infection 100:112 HIV Infection 100:112 Molecular Characteristics of the Envelope of Vertically Transmitted HIV-1 Strains from Infants with HIV Infection. 28401776 1 5 theme host 238:241 arg1 environment 243:253 the host environment 234:253 the host environment to which the virus has partially adapted 234:294 Mother-to-child transmission (MTCT) of HIV offers a good opportunity to study the dynamics of early viral evolution in the host environment to which the virus has partially adapted. 28401776 6 6 located observed 1067:1074 arg2 charge 1056:1061 a stable net charge 1043:1061 a stable net charge 1043:1061 Further, a stable net charge was observed in the V2 and V3 regions prompting us to speculate on the established interaction of the transmitted variant with the integrin α4β7 receptor and R5 co-receptor, respectively. 28401776 6 6 located observed 1067:1074 arg1 V3 1090:1091 V3 1090:1091 V3 1090:1091 Further, a stable net charge was observed in the V2 and V3 regions prompting us to speculate on the established interaction of the transmitted variant with the integrin α4β7 receptor and R5 co-receptor, respectively. 28401776 6 6 located observed 1067:1074 arg1 V2 1083:1084 V2 1083:1084 V2 1083:1084 Further, a stable net charge was observed in the V2 and V3 regions prompting us to speculate on the established interaction of the transmitted variant with the integrin α4β7 receptor and R5 co-receptor, respectively. 28401776 7 7 from stages 1595:1600 arg1 MTCT 1618:1621 MTCT 1618:1621 MTCT 1618:1621 In brief, our observations suggest that differences in the length of the variable regions and variation in the frequency of PNGS in the envelope of the viruses obtained from very recently infected individuals in our population could be important characteristics of the unique quasispecies that is responsible for the spread of HIV in the early stages of infection in MTCT. 28401776 7 7 from stages 1595:1600 arg1 spread 1568:1573 the spread 1564:1573 the spread of HIV in the early stages of infection in MTCT 1564:1621 In brief, our observations suggest that differences in the length of the variable regions and variation in the frequency of PNGS in the envelope of the viruses obtained from very recently infected individuals in our population could be important characteristics of the unique quasispecies that is responsible for the spread of HIV in the early stages of infection in MTCT. 28401776 3 8 from infants 629:635 arg1 divergence 565:574 the genetic divergence 553:574 the genetic divergence of proviral envelope sequences from the HIV-infected infants (<2 years) 553:646 Therefore, we undertook a study to determine the genetic divergence of proviral envelope sequences from the HIV-infected infants (<2 years). 28401776 3 8 from infants 629:635 arg1 sequences 597:605 proviral envelope sequences 579:605 proviral envelope sequences from the HIV-infected infants (<2 years) 579:646 Therefore, we undertook a study to determine the genetic divergence of proviral envelope sequences from the HIV-infected infants (<2 years). 28401776 1 9 theme good 167:170 arg1 opportunity 172:182 a good opportunity 165:182 a good opportunity to study the dynamics of early viral evolution in the host environment to which the virus has partially adapted 165:294 Mother-to-child transmission (MTCT) of HIV offers a good opportunity to study the dynamics of early viral evolution in the host environment to which the virus has partially adapted. 28401776 7 10 from infection 1605:1613 arg1 MTCT 1618:1621 MTCT 1618:1621 MTCT 1618:1621 In brief, our observations suggest that differences in the length of the variable regions and variation in the frequency of PNGS in the envelope of the viruses obtained from very recently infected individuals in our population could be important characteristics of the unique quasispecies that is responsible for the spread of HIV in the early stages of infection in MTCT. 28401776 7 11 from variation 1345:1353 arg1 frequency 1362:1370 the frequency 1358:1370 the frequency of PNGS in the envelope of the viruses obtained from very recently infected individuals in our population 1358:1476 In brief, our observations suggest that differences in the length of the variable regions and variation in the frequency of PNGS in the envelope of the viruses obtained from very recently infected individuals in our population could be important characteristics of the unique quasispecies that is responsible for the spread of HIV in the early stages of infection in MTCT. 28401776 7 11 from variation 1345:1353 arg1 length 1310:1315 the length 1306:1315 the length of the variable regions 1306:1339 In brief, our observations suggest that differences in the length of the variable regions and variation in the frequency of PNGS in the envelope of the viruses obtained from very recently infected individuals in our population could be important characteristics of the unique quasispecies that is responsible for the spread of HIV in the early stages of infection in MTCT. 28401776 6 12 theme net 1052:1054 arg1 charge 1056:1061 a stable net charge 1043:1061 a stable net charge 1043:1061 Further, a stable net charge was observed in the V2 and V3 regions prompting us to speculate on the established interaction of the transmitted variant with the integrin α4β7 receptor and R5 co-receptor, respectively. 28401776 7 13 theme unique 1520:1525 arg1 quasispecies 1527:1538 the unique quasispecies 1516:1538 the unique quasispecies that is responsible for the spread of HIV in the early stages of infection in MTCT 1516:1621 In brief, our observations suggest that differences in the length of the variable regions and variation in the frequency of PNGS in the envelope of the viruses obtained from very recently infected individuals in our population could be important characteristics of the unique quasispecies that is responsible for the spread of HIV in the early stages of infection in MTCT. 28401776 7 13 theme unique 1520:1525 arg1 responsible 1548:1558 responsible 1548:1558 responsible 1548:1558 In brief, our observations suggest that differences in the length of the variable regions and variation in the frequency of PNGS in the envelope of the viruses obtained from very recently infected individuals in our population could be important characteristics of the unique quasispecies that is responsible for the spread of HIV in the early stages of infection in MTCT. 28401776 6 14 dep V2 1083:1084 arg1 regions 1093:1099 regions 1093:1099 regions 1093:1099 Further, a stable net charge was observed in the V2 and V3 regions prompting us to speculate on the established interaction of the transmitted variant with the integrin α4β7 receptor and R5 co-receptor, respectively. 28401776 6 14 dep V2 1083:1084 arg1 the 1079:1081 the 1079:1081 the 1079:1081 Further, a stable net charge was observed in the V2 and V3 regions prompting us to speculate on the established interaction of the transmitted variant with the integrin α4β7 receptor and R5 co-receptor, respectively. 28401776 5 15 theme fitness 991:997 arg1 disadvantage 999:1010 a fitness disadvantage 989:1010 a fitness disadvantage in the variant forms 989:1031 Surprisingly, frequency of PNGS in the V5 region was found to revert rapidly, in about 75% of the sequences, which could surmise a fitness disadvantage in the variant forms. 28401776 4 16 from difference 793:802 arg1 length 807:812 length 807:812 length of the V1V2 region of the envelope sequences 807:857 Detailed analysis revealed unique features of potential N-linked glycosylation sites (PNGS) and their frequency of occurrence that built on the difference in length of the V1V2 region of the envelope sequences. 28401776 4 17 theme sequences 849:857 arg1 region 826:831 the V1V2 region 817:831 the V1V2 region of the envelope sequences 817:857 Detailed analysis revealed unique features of potential N-linked glycosylation sites (PNGS) and their frequency of occurrence that built on the difference in length of the V1V2 region of the envelope sequences. 28401776 6 18 theme α4β7 1203:1206 arg1 receptor 1208:1215 the integrin α4β7 receptor 1190:1215 the integrin α4β7 receptor 1190:1215 Further, a stable net charge was observed in the V2 and V3 regions prompting us to speculate on the established interaction of the transmitted variant with the integrin α4β7 receptor and R5 co-receptor, respectively. 28401776 5 19 theme sequences 958:966 arg1 % 949:949 about 75% 941:949 about 75% of the sequences, which could surmise a fitness disadvantage in the variant forms 941:1031 Surprisingly, frequency of PNGS in the V5 region was found to revert rapidly, in about 75% of the sequences, which could surmise a fitness disadvantage in the variant forms. 28401776 5 19 theme sequences 958:966 arg1 sequences 958:966 the sequences 954:966 the sequences 954:966 Surprisingly, frequency of PNGS in the V5 region was found to revert rapidly, in about 75% of the sequences, which could surmise a fitness disadvantage in the variant forms. 28401776 7 20 theme important 1487:1495 arg1 characteristics 1497:1511 important characteristics 1487:1511 important characteristics of the unique quasispecies that is responsible for the spread of HIV in the early stages of infection in MTCT 1487:1621 In brief, our observations suggest that differences in the length of the variable regions and variation in the frequency of PNGS in the envelope of the viruses obtained from very recently infected individuals in our population could be important characteristics of the unique quasispecies that is responsible for the spread of HIV in the early stages of infection in MTCT. 28401776 7 21 from spread 1568:1573 arg1 stages 1595:1600 the early stages 1585:1600 the early stages of infection in MTCT 1585:1621 In brief, our observations suggest that differences in the length of the variable regions and variation in the frequency of PNGS in the envelope of the viruses obtained from very recently infected individuals in our population could be important characteristics of the unique quasispecies that is responsible for the spread of HIV in the early stages of infection in MTCT. 28401776 4 22 theme potential 695:703 arg1 sites 728:732 potential N-linked glycosylation sites 695:732 potential N-linked glycosylation sites (PNGS) 695:739 Detailed analysis revealed unique features of potential N-linked glycosylation sites (PNGS) and their frequency of occurrence that built on the difference in length of the V1V2 region of the envelope sequences. 28401776 4 22 theme potential 695:703 arg1 PNGS 735:738 PNGS 735:738 PNGS 735:738 Detailed analysis revealed unique features of potential N-linked glycosylation sites (PNGS) and their frequency of occurrence that built on the difference in length of the V1V2 region of the envelope sequences. 28401776 3 23 theme sequences 597:605 arg1 divergence 565:574 the genetic divergence 553:574 the genetic divergence of proviral envelope sequences from the HIV-infected infants (<2 years) 553:646 Therefore, we undertook a study to determine the genetic divergence of proviral envelope sequences from the HIV-infected infants (<2 years). 28401776 5 24 theme PNGS 887:890 arg1 frequency 874:882 frequency 874:882 frequency of PNGS in the V5 region 874:907 Surprisingly, frequency of PNGS in the V5 region was found to revert rapidly, in about 75% of the sequences, which could surmise a fitness disadvantage in the variant forms. 28401776 7 25 theme infection 1605:1613 arg1 stages 1595:1600 the early stages 1585:1600 the early stages of infection in MTCT 1585:1621 In brief, our observations suggest that differences in the length of the variable regions and variation in the frequency of PNGS in the envelope of the viruses obtained from very recently infected individuals in our population could be important characteristics of the unique quasispecies that is responsible for the spread of HIV in the early stages of infection in MTCT. 28401776 7 26 from HIV 1578:1580 arg1 stages 1595:1600 the early stages 1585:1600 the early stages of infection in MTCT 1585:1621 In brief, our observations suggest that differences in the length of the variable regions and variation in the frequency of PNGS in the envelope of the viruses obtained from very recently infected individuals in our population could be important characteristics of the unique quasispecies that is responsible for the spread of HIV in the early stages of infection in MTCT. 28401776 4 27 theme Detailed 649:656 arg1 analysis 658:665 Detailed analysis 649:665 Detailed analysis 649:665 Detailed analysis revealed unique features of potential N-linked glycosylation sites (PNGS) and their frequency of occurrence that built on the difference in length of the V1V2 region of the envelope sequences. 28401776 0 28 theme HIV-1 68:72 arg1 Strains 74:80 Vertically Transmitted HIV-1 Strains 45:80 Vertically Transmitted HIV-1 Strains from Infants with HIV Infection 45:112 Molecular Characteristics of the Envelope of Vertically Transmitted HIV-1 Strains from Infants with HIV Infection. 28401776 3 29 theme proviral 579:586 arg1 sequences 597:605 proviral envelope sequences 579:605 proviral envelope sequences from the HIV-infected infants (<2 years) 579:646 Therefore, we undertook a study to determine the genetic divergence of proviral envelope sequences from the HIV-infected infants (<2 years). 28401776 2 30 theme HIV 503:505 arg1 strains 492:498 the newly infecting and evolving strains 459:498 the newly infecting and evolving strains of HIV 459:505 Such studies would throw light on the unique features of the infecting viruses, which will subsequently help to design preventive or therapeutic measures against the newly infecting and evolving strains of HIV. 28401776 4 31 gly glycosylation 714:726 arg2 PNGS 735:738 PNGS 735:738 PNGS 735:738 Detailed analysis revealed unique features of potential N-linked glycosylation sites (PNGS) and their frequency of occurrence that built on the difference in length of the V1V2 region of the envelope sequences. 28401776 4 31 gly glycosylation 714:726 arg2 sites 728:732 potential N-linked glycosylation sites 695:732 potential N-linked glycosylation sites (PNGS) 695:739 Detailed analysis revealed unique features of potential N-linked glycosylation sites (PNGS) and their frequency of occurrence that built on the difference in length of the V1V2 region of the envelope sequences. 28401776 7 32 theme HIV 1578:1580 arg1 spread 1568:1573 the spread 1564:1573 the spread of HIV in the early stages of infection in MTCT 1564:1621 In brief, our observations suggest that differences in the length of the variable regions and variation in the frequency of PNGS in the envelope of the viruses obtained from very recently infected individuals in our population could be important characteristics of the unique quasispecies that is responsible for the spread of HIV in the early stages of infection in MTCT. 28401776 2 33 theme viruses 368:374 arg1 features 342:349 the unique features 331:349 the unique features of the infecting viruses, which will subsequently help to design preventive or therapeutic measures against the newly infecting and evolving strains of HIV 331:505 Such studies would throw light on the unique features of the infecting viruses, which will subsequently help to design preventive or therapeutic measures against the newly infecting and evolving strains of HIV. 28401776 5 34 theme variant 1019:1025 arg1 forms 1027:1031 the variant forms 1015:1031 the variant forms 1015:1031 Surprisingly, frequency of PNGS in the V5 region was found to revert rapidly, in about 75% of the sequences, which could surmise a fitness disadvantage in the variant forms. 28401776 2 35 theme preventive 416:425 arg1 measures 442:449 preventive or therapeutic measures 416:449 preventive or therapeutic measures against the newly infecting and evolving strains of HIV 416:505 Such studies would throw light on the unique features of the infecting viruses, which will subsequently help to design preventive or therapeutic measures against the newly infecting and evolving strains of HIV. 28401776 0 36 from Envelope 33:40 arg1 Infants 87:93 Infants 87:93 Infants with HIV Infection 87:112 Molecular Characteristics of the Envelope of Vertically Transmitted HIV-1 Strains from Infants with HIV Infection. 28401776 4 37 theme glycosylation 714:726 arg1 sites 728:732 potential N-linked glycosylation sites 695:732 potential N-linked glycosylation sites (PNGS) 695:739 Detailed analysis revealed unique features of potential N-linked glycosylation sites (PNGS) and their frequency of occurrence that built on the difference in length of the V1V2 region of the envelope sequences. 28401776 4 37 theme glycosylation 714:726 arg1 PNGS 735:738 PNGS 735:738 PNGS 735:738 Detailed analysis revealed unique features of potential N-linked glycosylation sites (PNGS) and their frequency of occurrence that built on the difference in length of the V1V2 region of the envelope sequences. 28401776 0 38 theme Molecular 0:8 arg1 Characteristics 10:24 Molecular Characteristics 0:24 Molecular Characteristics of the Envelope of Vertically Transmitted HIV-1 Strains from Infants with HIV Infection. 0:113 Molecular Characteristics of the Envelope of Vertically Transmitted HIV-1 Strains from Infants with HIV Infection. 28401776 3 39 from divergence 565:574 arg1 infants 629:635 the HIV-infected infants 612:635 the HIV-infected infants (<2 years) 612:646 Therefore, we undertook a study to determine the genetic divergence of proviral envelope sequences from the HIV-infected infants (<2 years). 28401776 3 39 from divergence 565:574 arg1 years 641:645 <2 years 638:645 <2 years 638:645 Therefore, we undertook a study to determine the genetic divergence of proviral envelope sequences from the HIV-infected infants (<2 years). 28401776 0 40 theme Envelope 33:40 arg1 Characteristics 10:24 Molecular Characteristics 0:24 Molecular Characteristics of the Envelope of Vertically Transmitted HIV-1 Strains from Infants with HIV Infection. 0:113 Molecular Characteristics of the Envelope of Vertically Transmitted HIV-1 Strains from Infants with HIV Infection. 28401776 7 41 from individuals 1448:1458 arg1 population 1467:1476 our population 1463:1476 our population 1463:1476 In brief, our observations suggest that differences in the length of the variable regions and variation in the frequency of PNGS in the envelope of the viruses obtained from very recently infected individuals in our population could be important characteristics of the unique quasispecies that is responsible for the spread of HIV in the early stages of infection in MTCT. 28401776 2 42 theme therapeutic 430:440 arg1 measures 442:449 preventive or therapeutic measures 416:449 preventive or therapeutic measures against the newly infecting and evolving strains of HIV 416:505 Such studies would throw light on the unique features of the infecting viruses, which will subsequently help to design preventive or therapeutic measures against the newly infecting and evolving strains of HIV. 28401776 5 43 from region 902:907 arg1 frequency 874:882 frequency 874:882 frequency of PNGS in the V5 region 874:907 Surprisingly, frequency of PNGS in the V5 region was found to revert rapidly, in about 75% of the sequences, which could surmise a fitness disadvantage in the variant forms. 28401776 1 44 theme early 209:213 arg1 evolution 221:229 early viral evolution 209:229 early viral evolution 209:229 Mother-to-child transmission (MTCT) of HIV offers a good opportunity to study the dynamics of early viral evolution in the host environment to which the virus has partially adapted. 28401776 1 45 theme evolution 221:229 arg1 dynamics 197:204 the dynamics 193:204 the dynamics of early viral evolution in the host environment to which the virus has partially adapted 193:294 Mother-to-child transmission (MTCT) of HIV offers a good opportunity to study the dynamics of early viral evolution in the host environment to which the virus has partially adapted. 28401776 4 46 theme V1V2 821:824 arg1 region 826:831 the V1V2 region 817:831 the V1V2 region of the envelope sequences 817:857 Detailed analysis revealed unique features of potential N-linked glycosylation sites (PNGS) and their frequency of occurrence that built on the difference in length of the V1V2 region of the envelope sequences. 28401776 4 47 link N-linked 705:712 arg1 sites 728:732 potential N-linked glycosylation sites 695:732 potential N-linked glycosylation sites (PNGS) 695:739 Detailed analysis revealed unique features of potential N-linked glycosylation sites (PNGS) and their frequency of occurrence that built on the difference in length of the V1V2 region of the envelope sequences. 28401776 4 47 link N-linked 705:712 arg1 PNGS 735:738 PNGS 735:738 PNGS 735:738 Detailed analysis revealed unique features of potential N-linked glycosylation sites (PNGS) and their frequency of occurrence that built on the difference in length of the V1V2 region of the envelope sequences. 28401776 6 48 theme transmitted 1165:1175 arg1 variant 1177:1183 the transmitted variant 1161:1183 the transmitted variant 1161:1183 Further, a stable net charge was observed in the V2 and V3 regions prompting us to speculate on the established interaction of the transmitted variant with the integrin α4β7 receptor and R5 co-receptor, respectively. 28401776 6 49 with interaction 1146:1156 arg1 receptor 1208:1215 the integrin α4β7 receptor 1190:1215 the integrin α4β7 receptor 1190:1215 Further, a stable net charge was observed in the V2 and V3 regions prompting us to speculate on the established interaction of the transmitted variant with the integrin α4β7 receptor and R5 co-receptor, respectively. 28401776 6 49 with interaction 1146:1156 arg1 co-receptor 1224:1234 R5 co-receptor 1221:1234 R5 co-receptor 1221:1234 Further, a stable net charge was observed in the V2 and V3 regions prompting us to speculate on the established interaction of the transmitted variant with the integrin α4β7 receptor and R5 co-receptor, respectively. 28401776 7 50 theme variable 1324:1331 arg1 regions 1333:1339 the variable regions 1320:1339 the variable regions 1320:1339 In brief, our observations suggest that differences in the length of the variable regions and variation in the frequency of PNGS in the envelope of the viruses obtained from very recently infected individuals in our population could be important characteristics of the unique quasispecies that is responsible for the spread of HIV in the early stages of infection in MTCT. 28401776 7 51 from MTCT 1618:1621 arg1 stages 1595:1600 the early stages 1585:1600 the early stages of infection in MTCT 1585:1621 In brief, our observations suggest that differences in the length of the variable regions and variation in the frequency of PNGS in the envelope of the viruses obtained from very recently infected individuals in our population could be important characteristics of the unique quasispecies that is responsible for the spread of HIV in the early stages of infection in MTCT. 28401776 7 52 theme regions 1333:1339 arg1 length 1310:1315 the length 1306:1315 the length of the variable regions 1306:1339 In brief, our observations suggest that differences in the length of the variable regions and variation in the frequency of PNGS in the envelope of the viruses obtained from very recently infected individuals in our population could be important characteristics of the unique quasispecies that is responsible for the spread of HIV in the early stages of infection in MTCT. 28401776 6 53 theme established 1134:1144 arg1 interaction 1146:1156 the established interaction 1130:1156 the established interaction of the transmitted variant with the integrin α4β7 receptor and R5 co-receptor, respectively 1130:1248 Further, a stable net charge was observed in the V2 and V3 regions prompting us to speculate on the established interaction of the transmitted variant with the integrin α4β7 receptor and R5 co-receptor, respectively. 28401776 2 54 theme Such 297:300 arg1 studies 302:308 Such studies 297:308 Such studies 297:308 Such studies would throw light on the unique features of the infecting viruses, which will subsequently help to design preventive or therapeutic measures against the newly infecting and evolving strains of HIV. 28401776 7 55 theme quasispecies 1527:1538 arg1 characteristics 1497:1511 important characteristics 1487:1511 important characteristics of the unique quasispecies that is responsible for the spread of HIV in the early stages of infection in MTCT 1487:1621 In brief, our observations suggest that differences in the length of the variable regions and variation in the frequency of PNGS in the envelope of the viruses obtained from very recently infected individuals in our population could be important characteristics of the unique quasispecies that is responsible for the spread of HIV in the early stages of infection in MTCT. 28401776 0 56 from Infants 87:93 arg1 Strains 74:80 Vertically Transmitted HIV-1 Strains 45:80 Vertically Transmitted HIV-1 Strains from Infants with HIV Infection 45:112 Molecular Characteristics of the Envelope of Vertically Transmitted HIV-1 Strains from Infants with HIV Infection. 28401776 0 56 from Infants 87:93 arg1 Envelope 33:40 the Envelope 29:40 the Envelope of Vertically Transmitted HIV-1 Strains from Infants with HIV Infection 29:112 Molecular Characteristics of the Envelope of Vertically Transmitted HIV-1 Strains from Infants with HIV Infection. 28401776 6 57 theme stable 1045:1050 arg1 charge 1056:1061 a stable net charge 1043:1061 a stable net charge 1043:1061 Further, a stable net charge was observed in the V2 and V3 regions prompting us to speculate on the established interaction of the transmitted variant with the integrin α4β7 receptor and R5 co-receptor, respectively. 28401776 6 58 theme R5 1221:1222 arg1 co-receptor 1224:1234 R5 co-receptor 1221:1234 R5 co-receptor 1221:1234 Further, a stable net charge was observed in the V2 and V3 regions prompting us to speculate on the established interaction of the transmitted variant with the integrin α4β7 receptor and R5 co-receptor, respectively. 28401776 3 59 theme genetic 557:563 arg1 divergence 565:574 the genetic divergence 553:574 the genetic divergence of proviral envelope sequences from the HIV-infected infants (<2 years) 553:646 Therefore, we undertook a study to determine the genetic divergence of proviral envelope sequences from the HIV-infected infants (<2 years). 28401776 7 60 from frequency 1362:1370 arg1 envelope 1387:1394 the envelope 1383:1394 the envelope of the viruses obtained from very recently infected individuals in our population 1383:1476 In brief, our observations suggest that differences in the length of the variable regions and variation in the frequency of PNGS in the envelope of the viruses obtained from very recently infected individuals in our population could be important characteristics of the unique quasispecies that is responsible for the spread of HIV in the early stages of infection in MTCT. 28401776 1 61 theme Mother-to-child 115:129 arg1 MTCT 145:148 MTCT 145:148 MTCT 145:148 Mother-to-child transmission (MTCT) of HIV offers a good opportunity to study the dynamics of early viral evolution in the host environment to which the virus has partially adapted. 28401776 1 61 theme Mother-to-child 115:129 arg1 transmission 131:142 Mother-to-child transmission 115:142 Mother-to-child transmission (MTCT) of HIV 115:156 Mother-to-child transmission (MTCT) of HIV offers a good opportunity to study the dynamics of early viral evolution in the host environment to which the virus has partially adapted. 28401776 7 62 from PNGS 1375:1378 arg1 envelope 1387:1394 the envelope 1383:1394 the envelope of the viruses obtained from very recently infected individuals in our population 1383:1476 In brief, our observations suggest that differences in the length of the variable regions and variation in the frequency of PNGS in the envelope of the viruses obtained from very recently infected individuals in our population could be important characteristics of the unique quasispecies that is responsible for the spread of HIV in the early stages of infection in MTCT. 28401776 4 63 theme envelope 840:847 arg1 sequences 849:857 the envelope sequences 836:857 the envelope sequences 836:857 Detailed analysis revealed unique features of potential N-linked glycosylation sites (PNGS) and their frequency of occurrence that built on the difference in length of the V1V2 region of the envelope sequences. 28401776 4 64 theme unique 676:681 arg1 features 683:690 unique features 676:690 unique features of potential N-linked glycosylation sites (PNGS) 676:739 Detailed analysis revealed unique features of potential N-linked glycosylation sites (PNGS) and their frequency of occurrence that built on the difference in length of the V1V2 region of the envelope sequences. 28401776 6 65 theme integrin 1194:1201 arg1 receptor 1208:1215 the integrin α4β7 receptor 1190:1215 the integrin α4β7 receptor 1190:1215 Further, a stable net charge was observed in the V2 and V3 regions prompting us to speculate on the established interaction of the transmitted variant with the integrin α4β7 receptor and R5 co-receptor, respectively. 28401776 3 66 theme envelope 588:595 arg1 sequences 597:605 proviral envelope sequences 579:605 proviral envelope sequences from the HIV-infected infants (<2 years) 579:646 Therefore, we undertook a study to determine the genetic divergence of proviral envelope sequences from the HIV-infected infants (<2 years). 28401776 7 67 from differences 1291:1301 arg1 frequency 1362:1370 the frequency 1358:1370 the frequency of PNGS in the envelope of the viruses obtained from very recently infected individuals in our population 1358:1476 In brief, our observations suggest that differences in the length of the variable regions and variation in the frequency of PNGS in the envelope of the viruses obtained from very recently infected individuals in our population could be important characteristics of the unique quasispecies that is responsible for the spread of HIV in the early stages of infection in MTCT. 28401776 7 67 from differences 1291:1301 arg1 length 1310:1315 the length 1306:1315 the length of the variable regions 1306:1339 In brief, our observations suggest that differences in the length of the variable regions and variation in the frequency of PNGS in the envelope of the viruses obtained from very recently infected individuals in our population could be important characteristics of the unique quasispecies that is responsible for the spread of HIV in the early stages of infection in MTCT. 28401776 0 68 theme Strains 74:80 arg1 Envelope 33:40 the Envelope 29:40 the Envelope of Vertically Transmitted HIV-1 Strains from Infants with HIV Infection 29:112 Molecular Characteristics of the Envelope of Vertically Transmitted HIV-1 Strains from Infants with HIV Infection. 28401776 2 69 theme infecting 469:477 arg1 strains 492:498 the newly infecting and evolving strains 459:498 the newly infecting and evolving strains of HIV 459:505 Such studies would throw light on the unique features of the infecting viruses, which will subsequently help to design preventive or therapeutic measures against the newly infecting and evolving strains of HIV. 28401776 5 70 from disadvantage 999:1010 arg1 forms 1027:1031 the variant forms 1015:1031 the variant forms 1015:1031 Surprisingly, frequency of PNGS in the V5 region was found to revert rapidly, in about 75% of the sequences, which could surmise a fitness disadvantage in the variant forms. 28401776 1 71 theme HIV 154:156 arg1 MTCT 145:148 MTCT 145:148 MTCT 145:148 Mother-to-child transmission (MTCT) of HIV offers a good opportunity to study the dynamics of early viral evolution in the host environment to which the virus has partially adapted. 28401776 1 71 theme HIV 154:156 arg1 transmission 131:142 Mother-to-child transmission 115:142 Mother-to-child transmission (MTCT) of HIV 115:156 Mother-to-child transmission (MTCT) of HIV offers a good opportunity to study the dynamics of early viral evolution in the host environment to which the virus has partially adapted. 28401776 7 72 theme infected 1439:1446 arg1 individuals 1448:1458 very recently infected individuals 1425:1458 very recently infected individuals in our population 1425:1476 In brief, our observations suggest that differences in the length of the variable regions and variation in the frequency of PNGS in the envelope of the viruses obtained from very recently infected individuals in our population could be important characteristics of the unique quasispecies that is responsible for the spread of HIV in the early stages of infection in MTCT. 28401776 0 73 theme HIV 100:102 arg1 Infection 104:112 HIV Infection 100:112 HIV Infection 100:112 Molecular Characteristics of the Envelope of Vertically Transmitted HIV-1 Strains from Infants with HIV Infection. 28401776 7 74 theme early 1589:1593 arg1 stages 1595:1600 the early stages 1585:1600 the early stages of infection in MTCT 1585:1621 In brief, our observations suggest that differences in the length of the variable regions and variation in the frequency of PNGS in the envelope of the viruses obtained from very recently infected individuals in our population could be important characteristics of the unique quasispecies that is responsible for the spread of HIV in the early stages of infection in MTCT. 28401776 2 75 theme evolving 483:490 arg1 strains 492:498 the newly infecting and evolving strains 459:498 the newly infecting and evolving strains of HIV 459:505 Such studies would throw light on the unique features of the infecting viruses, which will subsequently help to design preventive or therapeutic measures against the newly infecting and evolving strains of HIV. 28401776 2 76 theme infecting 358:366 arg1 viruses 368:374 the infecting viruses 354:374 the infecting viruses 354:374 Such studies would throw light on the unique features of the infecting viruses, which will subsequently help to design preventive or therapeutic measures against the newly infecting and evolving strains of HIV. 28401776 5 77 from PNGS 887:890 arg1 region 902:907 the V5 region 895:907 the V5 region 895:907 Surprisingly, frequency of PNGS in the V5 region was found to revert rapidly, in about 75% of the sequences, which could surmise a fitness disadvantage in the variant forms. 28401776 4 78 theme N-linked 705:712 arg1 sites 728:732 potential N-linked glycosylation sites 695:732 potential N-linked glycosylation sites (PNGS) 695:739 Detailed analysis revealed unique features of potential N-linked glycosylation sites (PNGS) and their frequency of occurrence that built on the difference in length of the V1V2 region of the envelope sequences. 28401776 4 78 theme N-linked 705:712 arg1 PNGS 735:738 PNGS 735:738 PNGS 735:738 Detailed analysis revealed unique features of potential N-linked glycosylation sites (PNGS) and their frequency of occurrence that built on the difference in length of the V1V2 region of the envelope sequences. 28401776 5 79 from frequency 874:882 arg1 region 902:907 the V5 region 895:907 the V5 region 895:907 Surprisingly, frequency of PNGS in the V5 region was found to revert rapidly, in about 75% of the sequences, which could surmise a fitness disadvantage in the variant forms. 28401776 5 80 theme V5 899:900 arg1 region 902:907 the V5 region 895:907 the V5 region 895:907 Surprisingly, frequency of PNGS in the V5 region was found to revert rapidly, in about 75% of the sequences, which could surmise a fitness disadvantage in the variant forms. 28401776 3 81 theme HIV-infected 616:627 arg1 infants 629:635 the HIV-infected infants 612:635 the HIV-infected infants (<2 years) 612:646 Therefore, we undertook a study to determine the genetic divergence of proviral envelope sequences from the HIV-infected infants (<2 years). 28401776 3 81 theme HIV-infected 616:627 arg1 years 641:645 <2 years 638:645 <2 years 638:645 Therefore, we undertook a study to determine the genetic divergence of proviral envelope sequences from the HIV-infected infants (<2 years). 28401776 4 82 theme sites 728:732 arg1 features 683:690 unique features 676:690 unique features of potential N-linked glycosylation sites (PNGS) 676:739 Detailed analysis revealed unique features of potential N-linked glycosylation sites (PNGS) and their frequency of occurrence that built on the difference in length of the V1V2 region of the envelope sequences. 28401776 4 82 theme sites 728:732 arg1 frequency 751:759 their frequency 745:759 their frequency of occurrence 745:773 Detailed analysis revealed unique features of potential N-linked glycosylation sites (PNGS) and their frequency of occurrence that built on the difference in length of the V1V2 region of the envelope sequences. 28401776 0 83 theme Transmitted 56:66 arg1 Strains 74:80 Vertically Transmitted HIV-1 Strains 45:80 Vertically Transmitted HIV-1 Strains from Infants with HIV Infection 45:112 Molecular Characteristics of the Envelope of Vertically Transmitted HIV-1 Strains from Infants with HIV Infection. 28401776 7 84 theme viruses 1403:1409 arg1 envelope 1387:1394 the envelope 1383:1394 the envelope of the viruses obtained from very recently infected individuals in our population 1383:1476 In brief, our observations suggest that differences in the length of the variable regions and variation in the frequency of PNGS in the envelope of the viruses obtained from very recently infected individuals in our population could be important characteristics of the unique quasispecies that is responsible for the spread of HIV in the early stages of infection in MTCT. 28401776 1 85 from dynamics 197:204 arg1 environment 243:253 the host environment 234:253 the host environment to which the virus has partially adapted 234:294 Mother-to-child transmission (MTCT) of HIV offers a good opportunity to study the dynamics of early viral evolution in the host environment to which the virus has partially adapted. 28401776 1 86 theme viral 215:219 arg1 evolution 221:229 early viral evolution 209:229 early viral evolution 209:229 Mother-to-child transmission (MTCT) of HIV offers a good opportunity to study the dynamics of early viral evolution in the host environment to which the virus has partially adapted. 28401776 4 87 theme occurrence 764:773 arg1 features 683:690 unique features 676:690 unique features of potential N-linked glycosylation sites (PNGS) 676:739 Detailed analysis revealed unique features of potential N-linked glycosylation sites (PNGS) and their frequency of occurrence that built on the difference in length of the V1V2 region of the envelope sequences. 28401776 4 87 theme occurrence 764:773 arg1 frequency 751:759 their frequency 745:759 their frequency of occurrence 745:773 Detailed analysis revealed unique features of potential N-linked glycosylation sites (PNGS) and their frequency of occurrence that built on the difference in length of the V1V2 region of the envelope sequences. 28401776 2 88 theme unique 335:340 arg1 features 342:349 the unique features 331:349 the unique features of the infecting viruses, which will subsequently help to design preventive or therapeutic measures against the newly infecting and evolving strains of HIV 331:505 Such studies would throw light on the unique features of the infecting viruses, which will subsequently help to design preventive or therapeutic measures against the newly infecting and evolving strains of HIV. 25263469 0 0 theme damage 97:102 arg1 pathway 113:119 the DNA damage response pathway 89:119 the DNA damage response pathway 89:119 Quantitative phosphoproteomics reveals crosstalk between phosphorylation and O-GlcNAc in the DNA damage response pathway. 25263469 5 1 theme 232 813:815 arg1 phosphosites 817:828 232 phosphosites 813:828 232 phosphosites 813:828 Quantitation of the phosphoproteome demonstrated that of 5529 phosphoserine, phosphothreonine, and phosphotyrosine sites, 232 phosphosites were upregulated and 133 downregulated in the absence of O-GlcNAc. 25263469 8 2 from changes 1276:1282 arg1 phosphoproteome 1291:1305 the phosphoproteome 1287:1305 the phosphoproteome 1287:1305 Together, these data support widespread changes in the phosphoproteome upon removal of O-GlcNAc, suggesting that O-GlcNAc regulates processes such as the cell cycle, genomic stability, and lysosomal biogenesis. 25263469 0 3 theme DNA 93:95 arg1 pathway 113:119 the DNA damage response pathway 89:119 the DNA damage response pathway 89:119 Quantitative phosphoproteomics reveals crosstalk between phosphorylation and O-GlcNAc in the DNA damage response pathway. 25263469 1 4 theme O-linked 187:194 arg1 O-GlcNAc 219:226 O-GlcNAc 219:226 O-GlcNAc 219:226 The modification of intracellular proteins by monosaccharides of O-linked β-N-acetylglucosamine (O-GlcNAc) is an essential and dynamic PTM of metazoans. 25263469 1 4 theme O-linked 187:194 arg1 β-N-acetylglucosamine 196:216 O-linked β-N-acetylglucosamine 187:216 O-linked β-N-acetylglucosamine (O-GlcNAc) 187:227 The modification of intracellular proteins by monosaccharides of O-linked β-N-acetylglucosamine (O-GlcNAc) is an essential and dynamic PTM of metazoans. 25263469 4 5 from comparisons 613:623 arg1 cells 684:688 OGT wild-type and Null cells 661:688 OGT wild-type and Null cells 661:688 To provide insight into the pathways regulated by O-GlcNAc, we have utilized SILAC-based quantitative proteomics to carry out comparisons of site-specific phosphorylation in OGT wild-type and Null cells. 25263469 4 6 used utilized 555:562 arg2 we 547:548 we 547:548 we 547:548 To provide insight into the pathways regulated by O-GlcNAc, we have utilized SILAC-based quantitative proteomics to carry out comparisons of site-specific phosphorylation in OGT wild-type and Null cells. 25263469 9 7 dep PXD001153 1518:1526 arg1 the 1482:1484 the 1482:1484 the 1482:1484 All MS data have been deposited in the ProteomeXchange with identifier PXD001153 (http://proteomecentral.proteomexchange.org/dataset/PXD001153). 25263469 9 7 dep PXD001153 1518:1526 arg1 ProteomeXchange 1486:1500 ProteomeXchange 1486:1500 ProteomeXchange 1486:1500 All MS data have been deposited in the ProteomeXchange with identifier PXD001153 (http://proteomecentral.proteomexchange.org/dataset/PXD001153). 25263469 6 8 theme response 1025:1032 arg1 proteins 1034:1041 response proteins 1025:1041 response proteins 1025:1041 Collectively, these data suggest that deletion of OGT has a profound effect on the phosphorylation of cell cycle and DNA damage response proteins. 25263469 0 9 theme response 104:111 arg1 pathway 113:119 the DNA damage response pathway 89:119 the DNA damage response pathway 89:119 Quantitative phosphoproteomics reveals crosstalk between phosphorylation and O-GlcNAc in the DNA damage response pathway. 25263469 6 10 theme OGT 947:949 arg1 deletion 935:942 deletion 935:942 deletion of OGT 935:949 Collectively, these data suggest that deletion of OGT has a profound effect on the phosphorylation of cell cycle and DNA damage response proteins. 25263469 2 11 theme O-GlcNAc 303:310 arg1 removal 292:298 removal 292:298 removal 292:298 The addition and removal of O-GlcNAc is catalyzed by the O-GlcNAc transferase (OGT) and O-GlcNAcase, respectively. 25263469 2 11 theme O-GlcNAc 303:310 arg1 addition 279:286 addition 279:286 addition 279:286 The addition and removal of O-GlcNAc is catalyzed by the O-GlcNAc transferase (OGT) and O-GlcNAcase, respectively. 25263469 6 12 theme damage 1018:1023 arg1 phosphorylation 980:994 the phosphorylation 976:994 the phosphorylation of cell cycle and DNA damage response proteins 976:1041 Collectively, these data suggest that deletion of OGT has a profound effect on the phosphorylation of cell cycle and DNA damage response proteins. 25263469 7 13 theme autophosphorylation 1140:1158 arg1 event 1160:1164 the activating autophosphorylation event 1125:1164 the activating autophosphorylation event on ATM (Ser1987) and on ATM's downstream targets p53, H2AX, and Chk2 1125:1233 Key events were confirmed by biochemical analyses and demonstrate an increase in the activating autophosphorylation event on ATM (Ser1987) and on ATM's downstream targets p53, H2AX, and Chk2. 25263469 5 14 theme O-GlcNAc 887:894 arg1 absence 876:882 the absence 872:882 the absence of O-GlcNAc 872:894 Quantitation of the phosphoproteome demonstrated that of 5529 phosphoserine, phosphothreonine, and phosphotyrosine sites, 232 phosphosites were upregulated and 133 downregulated in the absence of O-GlcNAc. 25263469 1 15 theme β-N-acetylglucosamine 196:216 arg1 monosaccharides 168:182 monosaccharides 168:182 monosaccharides of O-linked β-N-acetylglucosamine (O-GlcNAc) 168:227 The modification of intracellular proteins by monosaccharides of O-linked β-N-acetylglucosamine (O-GlcNAc) is an essential and dynamic PTM of metazoans. 25263469 5 16 theme phosphotyrosine 790:804 arg1 sites 806:810 phosphotyrosine sites 790:810 phosphotyrosine sites 790:810 Quantitation of the phosphoproteome demonstrated that of 5529 phosphoserine, phosphothreonine, and phosphotyrosine sites, 232 phosphosites were upregulated and 133 downregulated in the absence of O-GlcNAc. 25263469 9 17 theme identifier 1507:1516 arg1 PXD001153 1518:1526 identifier PXD001153 1507:1526 identifier PXD001153 (http://proteomecentral.proteomexchange.org/dataset/PXD001153) 1507:1589 All MS data have been deposited in the ProteomeXchange with identifier PXD001153 (http://proteomecentral.proteomexchange.org/dataset/PXD001153). 25263469 9 17 theme identifier 1507:1516 arg1 http 1529:1532 http://proteomecentral.proteomexchange.org/dataset/PXD001153 1529:1588 http://proteomecentral.proteomexchange.org/dataset/PXD001153 1529:1588 All MS data have been deposited in the ProteomeXchange with identifier PXD001153 (http://proteomecentral.proteomexchange.org/dataset/PXD001153). 25263469 6 18 theme cell 999:1002 arg1 cycle 1004:1008 cell cycle 999:1008 cell cycle 999:1008 Collectively, these data suggest that deletion of OGT has a profound effect on the phosphorylation of cell cycle and DNA damage response proteins. 25263469 6 19 theme DNA 1014:1016 arg1 damage 1018:1023 DNA damage 1014:1023 DNA damage 1014:1023 Collectively, these data suggest that deletion of OGT has a profound effect on the phosphorylation of cell cycle and DNA damage response proteins. 25263469 2 20 theme O-GlcNAc 332:339 arg1 OGT 354:356 OGT 354:356 OGT 354:356 The addition and removal of O-GlcNAc is catalyzed by the O-GlcNAc transferase (OGT) and O-GlcNAcase, respectively. 25263469 2 20 theme O-GlcNAc 332:339 arg1 transferase 341:351 O-GlcNAc transferase 332:351 O-GlcNAc transferase (OGT) 332:357 The addition and removal of O-GlcNAc is catalyzed by the O-GlcNAc transferase (OGT) and O-GlcNAcase, respectively. 25263469 8 21 theme widespread 1265:1274 arg1 changes 1276:1282 widespread changes 1265:1282 widespread changes in the phosphoproteome upon removal of O-GlcNAc 1265:1330 Together, these data support widespread changes in the phosphoproteome upon removal of O-GlcNAc, suggesting that O-GlcNAc regulates processes such as the cell cycle, genomic stability, and lysosomal biogenesis. 25263469 0 22 theme Quantitative 0:11 arg1 phosphoproteomics 13:29 Quantitative phosphoproteomics 0:29 Quantitative phosphoproteomics 0:29 Quantitative phosphoproteomics reveals crosstalk between phosphorylation and O-GlcNAc in the DNA damage response pathway. 25263469 4 23 theme SILAC-based 564:574 arg1 proteomics 589:598 SILAC-based quantitative proteomics 564:598 SILAC-based quantitative proteomics 564:598 To provide insight into the pathways regulated by O-GlcNAc, we have utilized SILAC-based quantitative proteomics to carry out comparisons of site-specific phosphorylation in OGT wild-type and Null cells. 25263469 7 24 theme activating 1129:1138 arg1 event 1160:1164 the activating autophosphorylation event 1125:1164 the activating autophosphorylation event on ATM (Ser1987) and on ATM's downstream targets p53, H2AX, and Chk2 1125:1233 Key events were confirmed by biochemical analyses and demonstrate an increase in the activating autophosphorylation event on ATM (Ser1987) and on ATM's downstream targets p53, H2AX, and Chk2. 25263469 2 25 dep addition 279:286 arg1 The 275:277 The 275:277 The 275:277 The addition and removal of O-GlcNAc is catalyzed by the O-GlcNAc transferase (OGT) and O-GlcNAcase, respectively. 25263469 9 26 theme MS 1451:1452 arg1 data 1454:1457 All MS data 1447:1457 All MS data 1447:1457 All MS data have been deposited in the ProteomeXchange with identifier PXD001153 (http://proteomecentral.proteomexchange.org/dataset/PXD001153). 25263469 4 27 theme wild-type 665:673 arg1 cells 684:688 OGT wild-type and Null cells 661:688 OGT wild-type and Null cells 661:688 To provide insight into the pathways regulated by O-GlcNAc, we have utilized SILAC-based quantitative proteomics to carry out comparisons of site-specific phosphorylation in OGT wild-type and Null cells. 25263469 7 28 theme downstream 1196:1205 arg1 targets 1207:1213 ATM's downstream targets p53, H2AX, and Chk2 1190:1233 ATM's downstream targets p53, H2AX, and Chk2 1190:1233 Key events were confirmed by biochemical analyses and demonstrate an increase in the activating autophosphorylation event on ATM (Ser1987) and on ATM's downstream targets p53, H2AX, and Chk2. 25263469 7 28 theme downstream 1196:1205 arg1 H2AX 1220:1223 H2AX 1220:1223 H2AX 1220:1223 Key events were confirmed by biochemical analyses and demonstrate an increase in the activating autophosphorylation event on ATM (Ser1987) and on ATM's downstream targets p53, H2AX, and Chk2. 25263469 7 28 theme downstream 1196:1205 arg1 Chk2 1230:1233 Chk2 1230:1233 Chk2 1230:1233 Key events were confirmed by biochemical analyses and demonstrate an increase in the activating autophosphorylation event on ATM (Ser1987) and on ATM's downstream targets p53, H2AX, and Chk2. 25263469 7 28 theme downstream 1196:1205 arg1 p53 1215:1217 p53 1215:1217 p53 1215:1217 Key events were confirmed by biochemical analyses and demonstrate an increase in the activating autophosphorylation event on ATM (Ser1987) and on ATM's downstream targets p53, H2AX, and Chk2. 25263469 6 29 theme cycle 1004:1008 arg1 phosphorylation 980:994 the phosphorylation 976:994 the phosphorylation of cell cycle and DNA damage response proteins 976:1041 Collectively, these data suggest that deletion of OGT has a profound effect on the phosphorylation of cell cycle and DNA damage response proteins. 25263469 1 30 link O-linked 187:194 arg1 O-GlcNAc 219:226 O-GlcNAc 219:226 O-GlcNAc 219:226 The modification of intracellular proteins by monosaccharides of O-linked β-N-acetylglucosamine (O-GlcNAc) is an essential and dynamic PTM of metazoans. 25263469 1 30 link O-linked 187:194 arg1 β-N-acetylglucosamine 196:216 O-linked β-N-acetylglucosamine 187:216 O-linked β-N-acetylglucosamine (O-GlcNAc) 187:227 The modification of intracellular proteins by monosaccharides of O-linked β-N-acetylglucosamine (O-GlcNAc) is an essential and dynamic PTM of metazoans. 25263469 6 31 theme profound 957:964 arg1 effect 966:971 a profound effect 955:971 a profound effect 955:971 Collectively, these data suggest that deletion of OGT has a profound effect on the phosphorylation of cell cycle and DNA damage response proteins. 25263469 4 32 theme OGT 661:663 arg1 cells 684:688 OGT wild-type and Null cells 661:688 OGT wild-type and Null cells 661:688 To provide insight into the pathways regulated by O-GlcNAc, we have utilized SILAC-based quantitative proteomics to carry out comparisons of site-specific phosphorylation in OGT wild-type and Null cells. 25263469 4 33 theme quantitative 576:587 arg1 proteomics 589:598 SILAC-based quantitative proteomics 564:598 SILAC-based quantitative proteomics 564:598 To provide insight into the pathways regulated by O-GlcNAc, we have utilized SILAC-based quantitative proteomics to carry out comparisons of site-specific phosphorylation in OGT wild-type and Null cells. 25263469 1 34 theme essential 235:243 arg1 modification 126:137 The modification 122:137 The modification of intracellular proteins by monosaccharides of O-linked β-N-acetylglucosamine (O-GlcNAc) 122:227 The modification of intracellular proteins by monosaccharides of O-linked β-N-acetylglucosamine (O-GlcNAc) is an essential and dynamic PTM of metazoans. 25263469 1 34 theme essential 235:243 arg1 PTM 257:259 an essential and dynamic PTM 232:259 an essential and dynamic PTM of metazoans 232:272 The modification of intracellular proteins by monosaccharides of O-linked β-N-acetylglucosamine (O-GlcNAc) is an essential and dynamic PTM of metazoans. 25263469 4 35 theme Null 679:682 arg1 cells 684:688 OGT wild-type and Null cells 661:688 OGT wild-type and Null cells 661:688 To provide insight into the pathways regulated by O-GlcNAc, we have utilized SILAC-based quantitative proteomics to carry out comparisons of site-specific phosphorylation in OGT wild-type and Null cells. 25263469 6 36 contain has 951:953 arg2 effect 966:971 a profound effect 955:971 a profound effect 955:971 Collectively, these data suggest that deletion of OGT has a profound effect on the phosphorylation of cell cycle and DNA damage response proteins. 25263469 6 36 contain has 951:953 arg1 deletion 935:942 deletion 935:942 deletion of OGT 935:949 Collectively, these data suggest that deletion of OGT has a profound effect on the phosphorylation of cell cycle and DNA damage response proteins. 25263469 8 37 theme genomic 1402:1408 arg1 stability 1410:1418 genomic stability 1402:1418 genomic stability 1402:1418 Together, these data support widespread changes in the phosphoproteome upon removal of O-GlcNAc, suggesting that O-GlcNAc regulates processes such as the cell cycle, genomic stability, and lysosomal biogenesis. 25263469 7 38 from ATM 1169:1171 arg1 increase 1113:1120 an increase 1110:1120 an increase in the activating autophosphorylation event on ATM (Ser1987) and on ATM's downstream targets p53, H2AX, and Chk2 1110:1233 Key events were confirmed by biochemical analyses and demonstrate an increase in the activating autophosphorylation event on ATM (Ser1987) and on ATM's downstream targets p53, H2AX, and Chk2. 25263469 8 39 theme cell 1390:1393 arg1 cycle 1395:1399 the cell cycle 1386:1399 the cell cycle 1386:1399 Together, these data support widespread changes in the phosphoproteome upon removal of O-GlcNAc, suggesting that O-GlcNAc regulates processes such as the cell cycle, genomic stability, and lysosomal biogenesis. 25263469 5 40 theme phosphoproteome 711:725 arg1 Quantitation 691:702 Quantitation 691:702 Quantitation of the phosphoproteome 691:725 Quantitation of the phosphoproteome demonstrated that of 5529 phosphoserine, phosphothreonine, and phosphotyrosine sites, 232 phosphosites were upregulated and 133 downregulated in the absence of O-GlcNAc. 25263469 6 41 dep cycle 1004:1008 arg1 proteins 1034:1041 response proteins 1025:1041 response proteins 1025:1041 Collectively, these data suggest that deletion of OGT has a profound effect on the phosphorylation of cell cycle and DNA damage response proteins. 25263469 7 42 theme Key 1044:1046 arg1 events 1048:1053 Key events 1044:1053 Key events 1044:1053 Key events were confirmed by biochemical analyses and demonstrate an increase in the activating autophosphorylation event on ATM (Ser1987) and on ATM's downstream targets p53, H2AX, and Chk2. 25263469 7 43 dep targets 1207:1213 arg1 targets 1207:1213 ATM's downstream targets p53, H2AX, and Chk2 1190:1233 ATM's downstream targets p53, H2AX, and Chk2 1190:1233 Key events were confirmed by biochemical analyses and demonstrate an increase in the activating autophosphorylation event on ATM (Ser1987) and on ATM's downstream targets p53, H2AX, and Chk2. 25263469 7 43 dep targets 1207:1213 arg1 H2AX 1220:1223 H2AX 1220:1223 H2AX 1220:1223 Key events were confirmed by biochemical analyses and demonstrate an increase in the activating autophosphorylation event on ATM (Ser1987) and on ATM's downstream targets p53, H2AX, and Chk2. 25263469 7 43 dep targets 1207:1213 arg1 Chk2 1230:1233 Chk2 1230:1233 Chk2 1230:1233 Key events were confirmed by biochemical analyses and demonstrate an increase in the activating autophosphorylation event on ATM (Ser1987) and on ATM's downstream targets p53, H2AX, and Chk2. 25263469 7 43 dep targets 1207:1213 arg1 p53 1215:1217 p53 1215:1217 p53 1215:1217 Key events were confirmed by biochemical analyses and demonstrate an increase in the activating autophosphorylation event on ATM (Ser1987) and on ATM's downstream targets p53, H2AX, and Chk2. 25263469 1 44 theme intracellular 142:154 arg1 proteins 156:163 intracellular proteins 142:163 intracellular proteins 142:163 The modification of intracellular proteins by monosaccharides of O-linked β-N-acetylglucosamine (O-GlcNAc) is an essential and dynamic PTM of metazoans. 25263469 1 45 theme dynamic 249:255 arg1 modification 126:137 The modification 122:137 The modification of intracellular proteins by monosaccharides of O-linked β-N-acetylglucosamine (O-GlcNAc) 122:227 The modification of intracellular proteins by monosaccharides of O-linked β-N-acetylglucosamine (O-GlcNAc) is an essential and dynamic PTM of metazoans. 25263469 1 45 theme dynamic 249:255 arg1 PTM 257:259 an essential and dynamic PTM 232:259 an essential and dynamic PTM of metazoans 232:272 The modification of intracellular proteins by monosaccharides of O-linked β-N-acetylglucosamine (O-GlcNAc) is an essential and dynamic PTM of metazoans. 25263469 7 46 theme biochemical 1073:1083 arg1 analyses 1085:1092 biochemical analyses 1073:1092 biochemical analyses 1073:1092 Key events were confirmed by biochemical analyses and demonstrate an increase in the activating autophosphorylation event on ATM (Ser1987) and on ATM's downstream targets p53, H2AX, and Chk2. 25263469 8 47 theme lysosomal 1425:1433 arg1 biogenesis 1435:1444 lysosomal biogenesis 1425:1444 lysosomal biogenesis 1425:1444 Together, these data support widespread changes in the phosphoproteome upon removal of O-GlcNAc, suggesting that O-GlcNAc regulates processes such as the cell cycle, genomic stability, and lysosomal biogenesis. 25263469 7 48 from event 1160:1164 arg1 ATM 1169:1171 ATM 1169:1171 ATM (Ser1987) 1169:1181 Key events were confirmed by biochemical analyses and demonstrate an increase in the activating autophosphorylation event on ATM (Ser1987) and on ATM's downstream targets p53, H2AX, and Chk2. 25263469 7 48 from event 1160:1164 arg1 Ser1987 1174:1180 Ser1987 1174:1180 Ser1987 1174:1180 Key events were confirmed by biochemical analyses and demonstrate an increase in the activating autophosphorylation event on ATM (Ser1987) and on ATM's downstream targets p53, H2AX, and Chk2. 25263469 1 49 theme proteins 156:163 arg1 modification 126:137 The modification 122:137 The modification of intracellular proteins by monosaccharides of O-linked β-N-acetylglucosamine (O-GlcNAc) 122:227 The modification of intracellular proteins by monosaccharides of O-linked β-N-acetylglucosamine (O-GlcNAc) is an essential and dynamic PTM of metazoans. 25263469 1 49 theme proteins 156:163 arg1 PTM 257:259 an essential and dynamic PTM 232:259 an essential and dynamic PTM of metazoans 232:272 The modification of intracellular proteins by monosaccharides of O-linked β-N-acetylglucosamine (O-GlcNAc) is an essential and dynamic PTM of metazoans. 25263469 8 50 theme O-GlcNAc 1323:1330 arg1 removal 1312:1318 removal 1312:1318 removal of O-GlcNAc 1312:1330 Together, these data support widespread changes in the phosphoproteome upon removal of O-GlcNAc, suggesting that O-GlcNAc regulates processes such as the cell cycle, genomic stability, and lysosomal biogenesis. 25263469 7 51 from increase 1113:1120 arg1 ATM 1169:1171 ATM 1169:1171 ATM (Ser1987) 1169:1181 Key events were confirmed by biochemical analyses and demonstrate an increase in the activating autophosphorylation event on ATM (Ser1987) and on ATM's downstream targets p53, H2AX, and Chk2. 25263469 7 51 from increase 1113:1120 arg1 event 1160:1164 the activating autophosphorylation event 1125:1164 the activating autophosphorylation event on ATM (Ser1987) and on ATM's downstream targets p53, H2AX, and Chk2 1125:1233 Key events were confirmed by biochemical analyses and demonstrate an increase in the activating autophosphorylation event on ATM (Ser1987) and on ATM's downstream targets p53, H2AX, and Chk2. 25263469 7 51 from increase 1113:1120 arg1 Ser1987 1174:1180 Ser1987 1174:1180 Ser1987 1174:1180 Key events were confirmed by biochemical analyses and demonstrate an increase in the activating autophosphorylation event on ATM (Ser1987) and on ATM's downstream targets p53, H2AX, and Chk2. 25263469 1 52 theme metazoans 264:272 arg1 modification 126:137 The modification 122:137 The modification of intracellular proteins by monosaccharides of O-linked β-N-acetylglucosamine (O-GlcNAc) 122:227 The modification of intracellular proteins by monosaccharides of O-linked β-N-acetylglucosamine (O-GlcNAc) is an essential and dynamic PTM of metazoans. 25263469 1 52 theme metazoans 264:272 arg1 PTM 257:259 an essential and dynamic PTM 232:259 an essential and dynamic PTM of metazoans 232:272 The modification of intracellular proteins by monosaccharides of O-linked β-N-acetylglucosamine (O-GlcNAc) is an essential and dynamic PTM of metazoans. 25263469 4 53 theme site-specific 628:640 arg1 phosphorylation 642:656 site-specific phosphorylation 628:656 site-specific phosphorylation 628:656 To provide insight into the pathways regulated by O-GlcNAc, we have utilized SILAC-based quantitative proteomics to carry out comparisons of site-specific phosphorylation in OGT wild-type and Null cells. 25263469 4 54 theme phosphorylation 642:656 arg1 comparisons 613:623 comparisons 613:623 comparisons of site-specific phosphorylation in OGT wild-type and Null cells 613:688 To provide insight into the pathways regulated by O-GlcNAc, we have utilized SILAC-based quantitative proteomics to carry out comparisons of site-specific phosphorylation in OGT wild-type and Null cells. 27421773 9 0 theme binding 1445:1451 arg1 toxin 1461:1465 toxin 1461:1465 toxin 1461:1465 Our findings suggest that specific mutations in the binding site of toxin are potentially preventing the formation of stable complex of receptor-toxin, which might lead to mechanism of resistance. 27421773 9 0 theme binding 1445:1451 arg1 site 1453:1456 the binding site 1441:1456 the binding site of toxin 1441:1465 Our findings suggest that specific mutations in the binding site of toxin are potentially preventing the formation of stable complex of receptor-toxin, which might lead to mechanism of resistance. 27421773 6 1 theme Residue 932:938 arg1 variations 940:949 Residue variations 932:949 Residue variations at key positions 932:966 Residue variations at key positions alter the secondary structure of binding cleft, which might interfere with toxin binding and it could be one of the possible explanations for the resistance to snake venoms. 27421773 5 2 gly glycosylation 894:906 arg1 organisms 921:929 resistant organisms 911:929 resistant organisms 911:929 We have reported the potential glycosylation residues within the toxin-binding cleft adding sugar moieties through N-linked glycosylation in resistant organisms. 27421773 8 3 from variation 1248:1256 arg1 stability 1273:1281 the binding stability 1261:1281 the binding stability of Mongoose nAChR-α-Bungarotoxin (α-BTX) and human nAChR-α-BTX complexes 1261:1354 In addition, drastic variation in the binding stability of Mongoose nAChR-α-Bungarotoxin (α-BTX) and human nAChR-α-BTX complexes were found at specific phase of MDS. 27421773 10 4 theme interacting 1661:1671 arg1 residues 1673:1680 interacting residues 1661:1680 interacting residues 1661:1680 This in silico study on the binding cleft of nAChR and the findings of interacting residues will assist in designing potential inhibitors as therapeutic targets. 27421773 8 5 theme binding 1265:1271 arg1 stability 1273:1281 the binding stability 1261:1281 the binding stability of Mongoose nAChR-α-Bungarotoxin (α-BTX) and human nAChR-α-BTX complexes 1261:1354 In addition, drastic variation in the binding stability of Mongoose nAChR-α-Bungarotoxin (α-BTX) and human nAChR-α-BTX complexes were found at specific phase of MDS. 27421773 0 6 theme Molecular 0:8 arg1 modeling 10:17 Molecular modeling 0:17 Molecular modeling 0:17 Molecular modeling and structural analysis of nAChR variants uncovers the mechanism of resistance to snake toxins. 27421773 10 7 theme binding 1618:1624 arg1 cleft 1626:1630 the binding cleft 1614:1630 the binding cleft of nAChR and the findings of interacting residues 1614:1680 This in silico study on the binding cleft of nAChR and the findings of interacting residues will assist in designing potential inhibitors as therapeutic targets. 27421773 4 8 theme nAChRs 652:657 arg1 structures 614:623 structures 614:623 structures 614:623 In this study, we have analyzed the sequence and structures of toxin-binding/resistant nAChRs and their interaction stability with toxins through molecular docking and molecular dynamics simulation (MDS). 27421773 4 8 theme nAChRs 652:657 arg1 sequence 601:608 sequence 601:608 sequence 601:608 In this study, we have analyzed the sequence and structures of toxin-binding/resistant nAChRs and their interaction stability with toxins through molecular docking and molecular dynamics simulation (MDS). 27421773 6 9 theme binding 1001:1007 arg1 cleft 1009:1013 binding cleft 1001:1013 binding cleft 1001:1013 Residue variations at key positions alter the secondary structure of binding cleft, which might interfere with toxin binding and it could be one of the possible explanations for the resistance to snake venoms. 27421773 8 10 theme nAChR-α-Bungarotoxin 1295:1314 arg1 stability 1273:1281 the binding stability 1261:1281 the binding stability of Mongoose nAChR-α-Bungarotoxin (α-BTX) and human nAChR-α-BTX complexes 1261:1354 In addition, drastic variation in the binding stability of Mongoose nAChR-α-Bungarotoxin (α-BTX) and human nAChR-α-BTX complexes were found at specific phase of MDS. 27421773 4 11 theme molecular 733:741 arg1 simulation 752:761 molecular docking and molecular dynamics simulation 711:761 simulation 752:761 In this study, we have analyzed the sequence and structures of toxin-binding/resistant nAChRs and their interaction stability with toxins through molecular docking and molecular dynamics simulation (MDS). 27421773 3 12 theme resistance 543:552 arg1 organisms 554:562 resistance organisms 543:562 resistance organisms 543:562 The toxin-binding site of alpha subunit in the nAChRs is highly conserved throughout chordate lineages with few exceptions in resistance organisms. 27421773 8 13 theme drastic 1240:1246 arg1 variation 1248:1256 drastic variation 1240:1256 drastic variation in the binding stability of Mongoose nAChR-α-Bungarotoxin (α-BTX) and human nAChR-α-BTX complexes 1240:1354 In addition, drastic variation in the binding stability of Mongoose nAChR-α-Bungarotoxin (α-BTX) and human nAChR-α-BTX complexes were found at specific phase of MDS. 27421773 5 14 theme sugar 862:866 arg1 moieties 868:875 sugar moieties 862:875 sugar moieties 862:875 We have reported the potential glycosylation residues within the toxin-binding cleft adding sugar moieties through N-linked glycosylation in resistant organisms. 27421773 4 15 theme molecular 711:719 arg1 docking 721:727 molecular docking and molecular dynamics simulation 711:761 docking 721:727 In this study, we have analyzed the sequence and structures of toxin-binding/resistant nAChRs and their interaction stability with toxins through molecular docking and molecular dynamics simulation (MDS). 27421773 4 15 theme molecular 711:719 arg1 MDS 764:766 MDS 764:766 MDS 764:766 In this study, we have analyzed the sequence and structures of toxin-binding/resistant nAChRs and their interaction stability with toxins through molecular docking and molecular dynamics simulation (MDS). 27421773 1 16 theme Nicotinic 115:123 arg1 nAChRs 150:155 nAChRs 150:155 nAChRs 150:155 Nicotinic acetylcholine receptors (nAChRs) are neuromuscular proteins responsible for muscle contraction upon binding with chemical stimulant acetylcholine (ACh). 27421773 1 16 theme Nicotinic 115:123 arg1 receptors 139:147 Nicotinic acetylcholine receptors 115:147 Nicotinic acetylcholine receptors (nAChRs) 115:156 Nicotinic acetylcholine receptors (nAChRs) are neuromuscular proteins responsible for muscle contraction upon binding with chemical stimulant acetylcholine (ACh). 27421773 1 16 theme Nicotinic 115:123 arg1 proteins 176:183 neuromuscular proteins 162:183 neuromuscular proteins responsible for muscle contraction upon binding with chemical stimulant acetylcholine (ACh) 162:275 Nicotinic acetylcholine receptors (nAChRs) are neuromuscular proteins responsible for muscle contraction upon binding with chemical stimulant acetylcholine (ACh). 27421773 7 17 theme nAChR-α-neurotoxin 1154:1171 arg1 complexes 1173:1181 nAChR-α-neurotoxin complexes 1154:1181 nAChR-α-neurotoxin complexes 1154:1181 Analysis of nAChR-α-neurotoxin complexes has confirmed the key interacting residues. 27421773 4 18 theme interaction 669:679 arg1 stability 681:689 their interaction stability 663:689 their interaction stability 663:689 In this study, we have analyzed the sequence and structures of toxin-binding/resistant nAChRs and their interaction stability with toxins through molecular docking and molecular dynamics simulation (MDS). 27421773 8 19 theme nAChR-α-BTX 1334:1344 arg1 complexes 1346:1354 human nAChR-α-BTX complexes 1328:1354 human nAChR-α-BTX complexes 1328:1354 In addition, drastic variation in the binding stability of Mongoose nAChR-α-Bungarotoxin (α-BTX) and human nAChR-α-BTX complexes were found at specific phase of MDS. 27421773 3 20 theme few 525:527 arg1 exceptions 529:538 few exceptions 525:538 few exceptions in resistance organisms 525:562 The toxin-binding site of alpha subunit in the nAChRs is highly conserved throughout chordate lineages with few exceptions in resistance organisms. 27421773 1 21 theme acetylcholine 125:137 arg1 nAChRs 150:155 nAChRs 150:155 nAChRs 150:155 Nicotinic acetylcholine receptors (nAChRs) are neuromuscular proteins responsible for muscle contraction upon binding with chemical stimulant acetylcholine (ACh). 27421773 1 21 theme acetylcholine 125:137 arg1 receptors 139:147 Nicotinic acetylcholine receptors 115:147 Nicotinic acetylcholine receptors (nAChRs) 115:156 Nicotinic acetylcholine receptors (nAChRs) are neuromuscular proteins responsible for muscle contraction upon binding with chemical stimulant acetylcholine (ACh). 27421773 1 21 theme acetylcholine 125:137 arg1 proteins 176:183 neuromuscular proteins 162:183 neuromuscular proteins responsible for muscle contraction upon binding with chemical stimulant acetylcholine (ACh) 162:275 Nicotinic acetylcholine receptors (nAChRs) are neuromuscular proteins responsible for muscle contraction upon binding with chemical stimulant acetylcholine (ACh). 27421773 1 22 theme muscle 201:206 arg1 contraction 208:218 muscle contraction 201:218 muscle contraction upon binding with chemical stimulant acetylcholine (ACh) 201:275 Nicotinic acetylcholine receptors (nAChRs) are neuromuscular proteins responsible for muscle contraction upon binding with chemical stimulant acetylcholine (ACh). 27421773 4 23 theme stability 681:689 arg1 structures 614:623 structures 614:623 structures 614:623 In this study, we have analyzed the sequence and structures of toxin-binding/resistant nAChRs and their interaction stability with toxins through molecular docking and molecular dynamics simulation (MDS). 27421773 4 23 theme stability 681:689 arg1 sequence 601:608 sequence 601:608 sequence 601:608 In this study, we have analyzed the sequence and structures of toxin-binding/resistant nAChRs and their interaction stability with toxins through molecular docking and molecular dynamics simulation (MDS). 27421773 5 24 theme resistant 911:919 arg1 organisms 921:929 resistant organisms 911:929 resistant organisms 911:929 We have reported the potential glycosylation residues within the toxin-binding cleft adding sugar moieties through N-linked glycosylation in resistant organisms. 27421773 3 25 from exceptions 529:538 arg1 organisms 554:562 resistance organisms 543:562 resistance organisms 543:562 The toxin-binding site of alpha subunit in the nAChRs is highly conserved throughout chordate lineages with few exceptions in resistance organisms. 27421773 0 26 theme resistance 87:96 arg1 mechanism 74:82 the mechanism 70:82 the mechanism of resistance to snake toxins 70:112 Molecular modeling and structural analysis of nAChR variants uncovers the mechanism of resistance to snake toxins. 27421773 8 27 theme MDS 1388:1390 arg1 phase 1379:1383 specific phase 1370:1383 specific phase of MDS 1370:1390 In addition, drastic variation in the binding stability of Mongoose nAChR-α-Bungarotoxin (α-BTX) and human nAChR-α-BTX complexes were found at specific phase of MDS. 27421773 10 28 theme residues 1673:1680 arg1 nAChR 1635:1639 nAChR 1635:1639 nAChR 1635:1639 This in silico study on the binding cleft of nAChR and the findings of interacting residues will assist in designing potential inhibitors as therapeutic targets. 27421773 10 28 theme residues 1673:1680 arg1 findings 1649:1656 the findings 1645:1656 the findings of interacting residues 1645:1680 This in silico study on the binding cleft of nAChR and the findings of interacting residues will assist in designing potential inhibitors as therapeutic targets. 27421773 0 29 theme snake 101:105 arg1 toxins 107:112 snake toxins 101:112 snake toxins 101:112 Molecular modeling and structural analysis of nAChR variants uncovers the mechanism of resistance to snake toxins. 27421773 3 30 with lineages 511:518 arg1 exceptions 529:538 few exceptions 525:538 few exceptions in resistance organisms 525:562 The toxin-binding site of alpha subunit in the nAChRs is highly conserved throughout chordate lineages with few exceptions in resistance organisms. 27421773 6 31 theme possible 1084:1091 arg1 explanations 1093:1104 the possible explanations 1080:1104 the possible explanations for the resistance to snake venoms 1080:1139 Residue variations at key positions alter the secondary structure of binding cleft, which might interfere with toxin binding and it could be one of the possible explanations for the resistance to snake venoms. 27421773 3 32 theme chordate 502:509 arg1 lineages 511:518 chordate lineages 502:518 chordate lineages with few exceptions in resistance organisms 502:562 The toxin-binding site of alpha subunit in the nAChRs is highly conserved throughout chordate lineages with few exceptions in resistance organisms. 27421773 4 33 theme dynamics 743:750 arg1 simulation 752:761 molecular docking and molecular dynamics simulation 711:761 simulation 752:761 In this study, we have analyzed the sequence and structures of toxin-binding/resistant nAChRs and their interaction stability with toxins through molecular docking and molecular dynamics simulation (MDS). 27421773 7 34 theme interacting 1205:1215 arg1 residues 1217:1224 the key interacting residues 1197:1224 the key interacting residues 1197:1224 Analysis of nAChR-α-neurotoxin complexes has confirmed the key interacting residues. 27421773 3 35 theme alpha 443:447 arg1 subunit 449:455 alpha subunit 443:455 alpha subunit 443:455 The toxin-binding site of alpha subunit in the nAChRs is highly conserved throughout chordate lineages with few exceptions in resistance organisms. 27421773 1 36 with binding 225:231 arg1 ACh 272:274 ACh 272:274 ACh 272:274 Nicotinic acetylcholine receptors (nAChRs) are neuromuscular proteins responsible for muscle contraction upon binding with chemical stimulant acetylcholine (ACh). 27421773 1 36 with binding 225:231 arg1 acetylcholine 257:269 chemical stimulant acetylcholine 238:269 chemical stimulant acetylcholine (ACh) 238:275 Nicotinic acetylcholine receptors (nAChRs) are neuromuscular proteins responsible for muscle contraction upon binding with chemical stimulant acetylcholine (ACh). 27421773 9 37 theme toxin 1461:1465 arg1 toxin 1461:1465 toxin 1461:1465 toxin 1461:1465 Our findings suggest that specific mutations in the binding site of toxin are potentially preventing the formation of stable complex of receptor-toxin, which might lead to mechanism of resistance. 27421773 9 37 theme toxin 1461:1465 arg1 site 1453:1456 the binding site 1441:1456 the binding site of toxin 1441:1465 Our findings suggest that specific mutations in the binding site of toxin are potentially preventing the formation of stable complex of receptor-toxin, which might lead to mechanism of resistance. 27421773 10 38 theme therapeutic 1731:1741 arg1 inhibitors 1717:1726 potential inhibitors 1707:1726 potential inhibitors 1707:1726 This in silico study on the binding cleft of nAChR and the findings of interacting residues will assist in designing potential inhibitors as therapeutic targets. 27421773 10 38 theme therapeutic 1731:1741 arg1 targets 1743:1749 therapeutic targets 1731:1749 therapeutic targets 1731:1749 This in silico study on the binding cleft of nAChR and the findings of interacting residues will assist in designing potential inhibitors as therapeutic targets. 27421773 5 39 theme potential 791:799 arg1 residues 815:822 the potential glycosylation residues 787:822 the potential glycosylation residues within the toxin-binding cleft adding sugar moieties through N-linked glycosylation in resistant organisms 787:929 We have reported the potential glycosylation residues within the toxin-binding cleft adding sugar moieties through N-linked glycosylation in resistant organisms. 27421773 4 40 dep sequence 601:608 arg1 the 597:599 the 597:599 the 597:599 In this study, we have analyzed the sequence and structures of toxin-binding/resistant nAChRs and their interaction stability with toxins through molecular docking and molecular dynamics simulation (MDS). 27421773 4 41 with structures 614:623 arg1 toxins 696:701 toxins 696:701 toxins 696:701 In this study, we have analyzed the sequence and structures of toxin-binding/resistant nAChRs and their interaction stability with toxins through molecular docking and molecular dynamics simulation (MDS). 27421773 10 42 from study 1605:1609 arg1 cleft 1626:1630 the binding cleft 1614:1630 the binding cleft of nAChR and the findings of interacting residues 1614:1680 This in silico study on the binding cleft of nAChR and the findings of interacting residues will assist in designing potential inhibitors as therapeutic targets. 27421773 6 43 theme snake 1128:1132 arg1 venoms 1134:1139 snake venoms 1128:1139 snake venoms 1128:1139 Residue variations at key positions alter the secondary structure of binding cleft, which might interfere with toxin binding and it could be one of the possible explanations for the resistance to snake venoms. 27421773 4 44 with sequence 601:608 arg1 toxins 696:701 toxins 696:701 toxins 696:701 In this study, we have analyzed the sequence and structures of toxin-binding/resistant nAChRs and their interaction stability with toxins through molecular docking and molecular dynamics simulation (MDS). 27421773 1 45 theme stimulant 247:255 arg1 ACh 272:274 ACh 272:274 ACh 272:274 Nicotinic acetylcholine receptors (nAChRs) are neuromuscular proteins responsible for muscle contraction upon binding with chemical stimulant acetylcholine (ACh). 27421773 1 45 theme stimulant 247:255 arg1 acetylcholine 257:269 chemical stimulant acetylcholine 238:269 chemical stimulant acetylcholine (ACh) 238:275 Nicotinic acetylcholine receptors (nAChRs) are neuromuscular proteins responsible for muscle contraction upon binding with chemical stimulant acetylcholine (ACh). 27421773 6 46 theme key 954:956 arg1 positions 958:966 key positions 954:966 key positions 954:966 Residue variations at key positions alter the secondary structure of binding cleft, which might interfere with toxin binding and it could be one of the possible explanations for the resistance to snake venoms. 27421773 2 47 theme snake 299:303 arg1 α-neurotoxins 282:294 The α-neurotoxins 278:294 The α-neurotoxins of snake 278:303 The α-neurotoxins of snake mimic the structure of ACh and attacks nAChRs, which block the flow of ACh and leads to numbness and paralysis. 27421773 10 48 theme in 1595:1596 arg1 study 1605:1609 This in silico study 1590:1609 This in silico study on the binding cleft of nAChR and the findings of interacting residues 1590:1680 This in silico study on the binding cleft of nAChR and the findings of interacting residues will assist in designing potential inhibitors as therapeutic targets. 27421773 1 49 theme responsible 185:195 arg1 receptors 139:147 Nicotinic acetylcholine receptors 115:147 Nicotinic acetylcholine receptors (nAChRs) 115:156 Nicotinic acetylcholine receptors (nAChRs) are neuromuscular proteins responsible for muscle contraction upon binding with chemical stimulant acetylcholine (ACh). 27421773 1 49 theme responsible 185:195 arg1 proteins 176:183 neuromuscular proteins 162:183 neuromuscular proteins responsible for muscle contraction upon binding with chemical stimulant acetylcholine (ACh) 162:275 Nicotinic acetylcholine receptors (nAChRs) are neuromuscular proteins responsible for muscle contraction upon binding with chemical stimulant acetylcholine (ACh). 27421773 1 50 theme neuromuscular 162:174 arg1 receptors 139:147 Nicotinic acetylcholine receptors 115:147 Nicotinic acetylcholine receptors (nAChRs) 115:156 Nicotinic acetylcholine receptors (nAChRs) are neuromuscular proteins responsible for muscle contraction upon binding with chemical stimulant acetylcholine (ACh). 27421773 1 50 theme neuromuscular 162:174 arg1 proteins 176:183 neuromuscular proteins 162:183 neuromuscular proteins responsible for muscle contraction upon binding with chemical stimulant acetylcholine (ACh) 162:275 Nicotinic acetylcholine receptors (nAChRs) are neuromuscular proteins responsible for muscle contraction upon binding with chemical stimulant acetylcholine (ACh). 27421773 0 51 theme nAChR 46:50 arg1 variants 52:59 nAChR variants 46:59 nAChR variants 46:59 Molecular modeling and structural analysis of nAChR variants uncovers the mechanism of resistance to snake toxins. 27421773 4 52 theme toxin-binding/resistant 628:650 arg1 nAChRs 652:657 toxin-binding/resistant nAChRs 628:657 toxin-binding/resistant nAChRs 628:657 In this study, we have analyzed the sequence and structures of toxin-binding/resistant nAChRs and their interaction stability with toxins through molecular docking and molecular dynamics simulation (MDS). 27421773 5 53 theme N-linked 885:892 arg1 glycosylation 894:906 N-linked glycosylation 885:906 N-linked glycosylation in resistant organisms 885:929 We have reported the potential glycosylation residues within the toxin-binding cleft adding sugar moieties through N-linked glycosylation in resistant organisms. 27421773 6 54 theme cleft 1009:1013 arg1 structure 988:996 the secondary structure 974:996 the secondary structure of binding cleft, which might interfere with toxin binding 974:1055 Residue variations at key positions alter the secondary structure of binding cleft, which might interfere with toxin binding and it could be one of the possible explanations for the resistance to snake venoms. 27421773 10 55 dep in 1595:1596 arg1 silico 1598:1603 silico 1598:1603 silico 1598:1603 This in silico study on the binding cleft of nAChR and the findings of interacting residues will assist in designing potential inhibitors as therapeutic targets. 27421773 5 56 theme toxin-binding 835:847 arg1 cleft 849:853 the toxin-binding cleft 831:853 the toxin-binding cleft adding sugar moieties through N-linked glycosylation in resistant organisms 831:929 We have reported the potential glycosylation residues within the toxin-binding cleft adding sugar moieties through N-linked glycosylation in resistant organisms. 27421773 8 57 theme Mongoose 1286:1293 arg1 nAChR-α-Bungarotoxin 1295:1314 Mongoose nAChR-α-Bungarotoxin 1286:1314 Mongoose nAChR-α-Bungarotoxin (α-BTX) 1286:1322 In addition, drastic variation in the binding stability of Mongoose nAChR-α-Bungarotoxin (α-BTX) and human nAChR-α-BTX complexes were found at specific phase of MDS. 27421773 8 57 theme Mongoose 1286:1293 arg1 α-BTX 1317:1321 α-BTX 1317:1321 α-BTX 1317:1321 In addition, drastic variation in the binding stability of Mongoose nAChR-α-Bungarotoxin (α-BTX) and human nAChR-α-BTX complexes were found at specific phase of MDS. 27421773 6 58 theme secondary 978:986 arg1 structure 988:996 the secondary structure 974:996 the secondary structure of binding cleft, which might interfere with toxin binding 974:1055 Residue variations at key positions alter the secondary structure of binding cleft, which might interfere with toxin binding and it could be one of the possible explanations for the resistance to snake venoms. 27421773 10 59 theme nAChR 1635:1639 arg1 cleft 1626:1630 the binding cleft 1614:1630 the binding cleft of nAChR and the findings of interacting residues 1614:1680 This in silico study on the binding cleft of nAChR and the findings of interacting residues will assist in designing potential inhibitors as therapeutic targets. 27421773 9 60 theme complex 1518:1524 arg1 formation 1498:1506 the formation 1494:1506 the formation of stable complex of receptor-toxin 1494:1542 Our findings suggest that specific mutations in the binding site of toxin are potentially preventing the formation of stable complex of receptor-toxin, which might lead to mechanism of resistance. 27421773 9 61 theme receptor-toxin 1529:1542 arg1 complex 1518:1524 stable complex 1511:1524 stable complex of receptor-toxin 1511:1542 Our findings suggest that specific mutations in the binding site of toxin are potentially preventing the formation of stable complex of receptor-toxin, which might lead to mechanism of resistance. 27421773 8 62 theme human 1328:1332 arg1 complexes 1346:1354 human nAChR-α-BTX complexes 1328:1354 human nAChR-α-BTX complexes 1328:1354 In addition, drastic variation in the binding stability of Mongoose nAChR-α-Bungarotoxin (α-BTX) and human nAChR-α-BTX complexes were found at specific phase of MDS. 27421773 5 63 from glycosylation 894:906 arg1 organisms 921:929 resistant organisms 911:929 resistant organisms 911:929 We have reported the potential glycosylation residues within the toxin-binding cleft adding sugar moieties through N-linked glycosylation in resistant organisms. 27421773 6 64 theme toxin 1043:1047 arg1 binding 1049:1055 toxin binding 1043:1055 toxin binding 1043:1055 Residue variations at key positions alter the secondary structure of binding cleft, which might interfere with toxin binding and it could be one of the possible explanations for the resistance to snake venoms. 27421773 8 65 theme complexes 1346:1354 arg1 stability 1273:1281 the binding stability 1261:1281 the binding stability of Mongoose nAChR-α-Bungarotoxin (α-BTX) and human nAChR-α-BTX complexes 1261:1354 In addition, drastic variation in the binding stability of Mongoose nAChR-α-Bungarotoxin (α-BTX) and human nAChR-α-BTX complexes were found at specific phase of MDS. 27421773 8 66 theme specific 1370:1377 arg1 phase 1379:1383 specific phase 1370:1383 specific phase of MDS 1370:1390 In addition, drastic variation in the binding stability of Mongoose nAChR-α-Bungarotoxin (α-BTX) and human nAChR-α-BTX complexes were found at specific phase of MDS. 27421773 2 67 theme ACh 328:330 arg1 structure 315:323 the structure 311:323 the structure 311:323 The α-neurotoxins of snake mimic the structure of ACh and attacks nAChRs, which block the flow of ACh and leads to numbness and paralysis. 27421773 5 68 link N-linked 885:892 arg1 glycosylation 894:906 N-linked glycosylation 885:906 N-linked glycosylation in resistant organisms 885:929 We have reported the potential glycosylation residues within the toxin-binding cleft adding sugar moieties through N-linked glycosylation in resistant organisms. 27421773 9 69 theme resistance 1578:1587 arg1 mechanism 1565:1573 mechanism 1565:1573 mechanism of resistance 1565:1587 Our findings suggest that specific mutations in the binding site of toxin are potentially preventing the formation of stable complex of receptor-toxin, which might lead to mechanism of resistance. 27421773 6 70 theme explanations 1093:1104 arg1 one 1073:1075 one 1073:1075 one 1073:1075 Residue variations at key positions alter the secondary structure of binding cleft, which might interfere with toxin binding and it could be one of the possible explanations for the resistance to snake venoms. 27421773 6 70 theme explanations 1093:1104 arg1 explanations 1093:1104 the possible explanations 1080:1104 the possible explanations for the resistance to snake venoms 1080:1139 Residue variations at key positions alter the secondary structure of binding cleft, which might interfere with toxin binding and it could be one of the possible explanations for the resistance to snake venoms. 27421773 1 71 theme chemical 238:245 arg1 ACh 272:274 ACh 272:274 ACh 272:274 Nicotinic acetylcholine receptors (nAChRs) are neuromuscular proteins responsible for muscle contraction upon binding with chemical stimulant acetylcholine (ACh). 27421773 1 71 theme chemical 238:245 arg1 acetylcholine 257:269 chemical stimulant acetylcholine 238:269 chemical stimulant acetylcholine (ACh) 238:275 Nicotinic acetylcholine receptors (nAChRs) are neuromuscular proteins responsible for muscle contraction upon binding with chemical stimulant acetylcholine (ACh). 27421773 2 72 theme ACh 376:378 arg1 flow 368:371 the flow 364:371 the flow of ACh 364:378 The α-neurotoxins of snake mimic the structure of ACh and attacks nAChRs, which block the flow of ACh and leads to numbness and paralysis. 27421773 5 73 theme glycosylation 801:813 arg1 residues 815:822 the potential glycosylation residues 787:822 the potential glycosylation residues within the toxin-binding cleft adding sugar moieties through N-linked glycosylation in resistant organisms 787:929 We have reported the potential glycosylation residues within the toxin-binding cleft adding sugar moieties through N-linked glycosylation in resistant organisms. 27421773 2 74 dep ACh 328:330 arg1 nAChRs 344:349 nAChRs 344:349 nAChRs 344:349 The α-neurotoxins of snake mimic the structure of ACh and attacks nAChRs, which block the flow of ACh and leads to numbness and paralysis. 27421773 10 75 theme findings 1649:1656 arg1 cleft 1626:1630 the binding cleft 1614:1630 the binding cleft of nAChR and the findings of interacting residues 1614:1680 This in silico study on the binding cleft of nAChR and the findings of interacting residues will assist in designing potential inhibitors as therapeutic targets. 27421773 0 76 theme structural 23:32 arg1 analysis 34:41 structural analysis 23:41 structural analysis 23:41 Molecular modeling and structural analysis of nAChR variants uncovers the mechanism of resistance to snake toxins. 27421773 3 77 theme subunit 449:455 arg1 site 435:438 The toxin-binding site 417:438 The toxin-binding site of alpha subunit in the nAChRs 417:469 The toxin-binding site of alpha subunit in the nAChRs is highly conserved throughout chordate lineages with few exceptions in resistance organisms. 27421773 3 77 theme subunit 449:455 arg1 subunit 449:455 alpha subunit 443:455 alpha subunit 443:455 The toxin-binding site of alpha subunit in the nAChRs is highly conserved throughout chordate lineages with few exceptions in resistance organisms. 27421773 7 78 theme complexes 1173:1181 arg1 Analysis 1142:1149 Analysis 1142:1149 Analysis of nAChR-α-neurotoxin complexes 1142:1181 Analysis of nAChR-α-neurotoxin complexes has confirmed the key interacting residues. 27421773 3 79 from site 435:438 arg1 nAChRs 464:469 the nAChRs 460:469 the nAChRs 460:469 The toxin-binding site of alpha subunit in the nAChRs is highly conserved throughout chordate lineages with few exceptions in resistance organisms. 27421773 0 80 theme variants 52:59 arg1 modeling 10:17 Molecular modeling 0:17 Molecular modeling 0:17 Molecular modeling and structural analysis of nAChR variants uncovers the mechanism of resistance to snake toxins. 27421773 0 80 theme variants 52:59 arg1 analysis 34:41 structural analysis 23:41 structural analysis 23:41 Molecular modeling and structural analysis of nAChR variants uncovers the mechanism of resistance to snake toxins. 27421773 9 81 from mutations 1428:1436 arg1 toxin 1461:1465 toxin 1461:1465 toxin 1461:1465 Our findings suggest that specific mutations in the binding site of toxin are potentially preventing the formation of stable complex of receptor-toxin, which might lead to mechanism of resistance. 27421773 9 81 from mutations 1428:1436 arg1 site 1453:1456 the binding site 1441:1456 the binding site of toxin 1441:1465 Our findings suggest that specific mutations in the binding site of toxin are potentially preventing the formation of stable complex of receptor-toxin, which might lead to mechanism of resistance. 27421773 6 82 from positions 958:966 arg1 variations 940:949 Residue variations 932:949 Residue variations at key positions 932:966 Residue variations at key positions alter the secondary structure of binding cleft, which might interfere with toxin binding and it could be one of the possible explanations for the resistance to snake venoms. 27421773 2 83 theme attacks 336:342 arg1 structure 315:323 the structure 311:323 the structure 311:323 The α-neurotoxins of snake mimic the structure of ACh and attacks nAChRs, which block the flow of ACh and leads to numbness and paralysis. 27421773 8 84 located found 1361:1365 arg2 variation 1248:1256 drastic variation 1240:1256 drastic variation in the binding stability of Mongoose nAChR-α-Bungarotoxin (α-BTX) and human nAChR-α-BTX complexes 1240:1354 In addition, drastic variation in the binding stability of Mongoose nAChR-α-Bungarotoxin (α-BTX) and human nAChR-α-BTX complexes were found at specific phase of MDS. 27421773 8 84 located found 1361:1365 arg1 addition 1230:1237 addition 1230:1237 addition 1230:1237 In addition, drastic variation in the binding stability of Mongoose nAChR-α-Bungarotoxin (α-BTX) and human nAChR-α-BTX complexes were found at specific phase of MDS. 27421773 8 84 located found 1361:1365 arg1 phase 1379:1383 specific phase 1370:1383 specific phase of MDS 1370:1390 In addition, drastic variation in the binding stability of Mongoose nAChR-α-Bungarotoxin (α-BTX) and human nAChR-α-BTX complexes were found at specific phase of MDS. 27421773 10 85 theme potential 1707:1715 arg1 inhibitors 1717:1726 potential inhibitors 1707:1726 potential inhibitors 1707:1726 This in silico study on the binding cleft of nAChR and the findings of interacting residues will assist in designing potential inhibitors as therapeutic targets. 27421773 10 85 theme potential 1707:1715 arg1 targets 1743:1749 therapeutic targets 1731:1749 therapeutic targets 1731:1749 This in silico study on the binding cleft of nAChR and the findings of interacting residues will assist in designing potential inhibitors as therapeutic targets. 27421773 9 86 theme specific 1419:1426 arg1 mutations 1428:1436 specific mutations 1419:1436 specific mutations in the binding site of toxin 1419:1465 Our findings suggest that specific mutations in the binding site of toxin are potentially preventing the formation of stable complex of receptor-toxin, which might lead to mechanism of resistance. 27421773 9 87 theme stable 1511:1516 arg1 complex 1518:1524 stable complex 1511:1524 stable complex of receptor-toxin 1511:1542 Our findings suggest that specific mutations in the binding site of toxin are potentially preventing the formation of stable complex of receptor-toxin, which might lead to mechanism of resistance. 27421773 3 88 theme toxin-binding 421:433 arg1 site 435:438 The toxin-binding site 417:438 The toxin-binding site of alpha subunit in the nAChRs 417:469 The toxin-binding site of alpha subunit in the nAChRs is highly conserved throughout chordate lineages with few exceptions in resistance organisms. 27421773 3 88 theme toxin-binding 421:433 arg1 subunit 449:455 alpha subunit 443:455 alpha subunit 443:455 The toxin-binding site of alpha subunit in the nAChRs is highly conserved throughout chordate lineages with few exceptions in resistance organisms. 27421773 7 89 theme key 1201:1203 arg1 residues 1217:1224 the key interacting residues 1197:1224 the key interacting residues 1197:1224 Analysis of nAChR-α-neurotoxin complexes has confirmed the key interacting residues. 24892637 3 0 theme G-like 331:336 arg1 SHBG 348:351 SHBG 348:351 SHBG 348:351 The N-terminal laminin G-like domain of SHBG includes binding sites for calcium, sex steroids, and fibulin family members, as well as a dimerization domain. 24892637 3 0 theme G-like 331:336 arg1 domain 338:343 The N-terminal laminin G-like domain 308:343 The N-terminal laminin G-like domain of SHBG 308:351 The N-terminal laminin G-like domain of SHBG includes binding sites for calcium, sex steroids, and fibulin family members, as well as a dimerization domain. 24892637 4 1 from properties 609:618 arg1 ways 631:634 ways 631:634 ways not previously recognized 631:660 We have found that 8 of 18 uncharacterized nonsynonymous single nucleotide polymorphisms within this domain alter the production or biochemical properties of SHBG in ways not previously recognized. 24892637 8 2 theme relative 1089:1096 arg1 affinity 1106:1113 the relative binding affinity 1085:1113 the relative binding affinity for estradiol 1085:1127 Two different substitutions within the dimer interface at R123 (R123H and R123C) reduce the affinity for 5α-dihydrotestosterone, while increasing the relative binding affinity for estradiol. 24892637 9 3 theme calcium 1156:1162 arg1 binding 1164:1170 calcium binding 1156:1170 calcium binding 1156:1170 SHBG T48I is defective in calcium binding, which leads to a defect in dimerization, reduced affinity for sex steroids, and an enhanced interaction with fibulin-2, which can all be restored by calcium supplementation. 24892637 9 4 theme reduced 1214:1220 arg1 affinity 1222:1229 reduced affinity 1214:1229 reduced affinity for sex steroids 1214:1246 SHBG T48I is defective in calcium binding, which leads to a defect in dimerization, reduced affinity for sex steroids, and an enhanced interaction with fibulin-2, which can all be restored by calcium supplementation. 24892637 9 5 theme enhanced 1256:1263 arg1 interaction 1265:1275 an enhanced interaction 1253:1275 an enhanced interaction with fibulin-2 1253:1290 SHBG T48I is defective in calcium binding, which leads to a defect in dimerization, reduced affinity for sex steroids, and an enhanced interaction with fibulin-2, which can all be restored by calcium supplementation. 24892637 5 6 theme O-Linked 663:670 arg1 glycosylation 672:684 O-Linked glycosylation 663:684 O-Linked glycosylation at Thr7 663:692 O-Linked glycosylation at Thr7 is disrupted in SHBG T7N, whereas abnormal glycosylation of SHBG G195E limits its secretion. 24892637 5 7 dep disrupted 697:705 arg1 whereas 720:726 whereas 720:726 whereas 720:726 O-Linked glycosylation at Thr7 is disrupted in SHBG T7N, whereas abnormal glycosylation of SHBG G195E limits its secretion. 24892637 4 8 from production 583:592 arg1 ways 631:634 ways 631:634 ways not previously recognized 631:660 We have found that 8 of 18 uncharacterized nonsynonymous single nucleotide polymorphisms within this domain alter the production or biochemical properties of SHBG in ways not previously recognized. 24892637 10 9 theme SHBG 1402:1405 arg1 structure 1407:1415 SHBG structure 1402:1415 SHBG structure 1402:1415 These naturally occurring mutants provide insight into SHBG structure and function, and defects in SHBG production or function need to be considered in the context of its utility as a biomarker of diseases. 24892637 8 10 theme dimer 978:982 arg1 interface 984:992 the dimer interface 974:992 the dimer interface 974:992 Two different substitutions within the dimer interface at R123 (R123H and R123C) reduce the affinity for 5α-dihydrotestosterone, while increasing the relative binding affinity for estradiol. 24892637 2 11 theme metabolic 288:296 arg1 syndrome 298:305 the metabolic syndrome 284:305 the metabolic syndrome 284:305 Several single nucleotide polymorphisms in the human SHBG gene have been linked to sex steroid-dependent diseases, including those associated with the metabolic syndrome. 24892637 9 12 from binding 1164:1170 arg1 defective 1143:1151 defective 1143:1151 defective 1143:1151 SHBG T48I is defective in calcium binding, which leads to a defect in dimerization, reduced affinity for sex steroids, and an enhanced interaction with fibulin-2, which can all be restored by calcium supplementation. 24892637 2 13 theme nucleotide 152:161 arg1 polymorphisms 163:175 Several single nucleotide polymorphisms 137:175 Several single nucleotide polymorphisms in the human SHBG gene 137:198 Several single nucleotide polymorphisms in the human SHBG gene have been linked to sex steroid-dependent diseases, including those associated with the metabolic syndrome. 24892637 8 14 dep R123 997:1000 arg1 R123C 1013:1017 R123C 1013:1017 R123C 1013:1017 Two different substitutions within the dimer interface at R123 (R123H and R123C) reduce the affinity for 5α-dihydrotestosterone, while increasing the relative binding affinity for estradiol. 24892637 8 14 dep R123 997:1000 arg1 R123H 1003:1007 R123H 1003:1007 R123H 1003:1007 Two different substitutions within the dimer interface at R123 (R123H and R123C) reduce the affinity for 5α-dihydrotestosterone, while increasing the relative binding affinity for estradiol. 24892637 9 15 from defective 1143:1151 arg1 binding 1164:1170 calcium binding 1156:1170 calcium binding 1156:1170 SHBG T48I is defective in calcium binding, which leads to a defect in dimerization, reduced affinity for sex steroids, and an enhanced interaction with fibulin-2, which can all be restored by calcium supplementation. 24892637 3 16 theme binding 362:368 arg1 sites 370:374 binding sites 362:374 binding sites 362:374 The N-terminal laminin G-like domain of SHBG includes binding sites for calcium, sex steroids, and fibulin family members, as well as a dimerization domain. 24892637 2 17 theme single 145:150 arg1 polymorphisms 163:175 Several single nucleotide polymorphisms 137:175 Several single nucleotide polymorphisms in the human SHBG gene 137:198 Several single nucleotide polymorphisms in the human SHBG gene have been linked to sex steroid-dependent diseases, including those associated with the metabolic syndrome. 24892637 6 18 theme SHBG 793:796 arg1 L165M 814:818 L165M 814:818 L165M 814:818 Three SHBG mutants (R135C, L165M, and E176K) bind estradiol with abnormally high affinity. 24892637 6 18 theme SHBG 793:796 arg1 E176K 825:829 E176K 825:829 E176K 825:829 Three SHBG mutants (R135C, L165M, and E176K) bind estradiol with abnormally high affinity. 24892637 6 18 theme SHBG 793:796 arg1 R135C 807:811 R135C 807:811 R135C 807:811 Three SHBG mutants (R135C, L165M, and E176K) bind estradiol with abnormally high affinity. 24892637 6 18 theme SHBG 793:796 arg1 mutants 798:804 Three SHBG mutants 787:804 Three SHBG mutants (R135C, L165M, and E176K) 787:830 Three SHBG mutants (R135C, L165M, and E176K) bind estradiol with abnormally high affinity. 24892637 9 19 with affinity 1222:1229 arg1 fibulin-2 1282:1290 fibulin-2 1282:1290 fibulin-2 1282:1290 SHBG T48I is defective in calcium binding, which leads to a defect in dimerization, reduced affinity for sex steroids, and an enhanced interaction with fibulin-2, which can all be restored by calcium supplementation. 24892637 2 20 attach linked 210:215 arg2 polymorphisms 163:175 Several single nucleotide polymorphisms 137:175 Several single nucleotide polymorphisms in the human SHBG gene 137:198 Several single nucleotide polymorphisms in the human SHBG gene have been linked to sex steroid-dependent diseases, including those associated with the metabolic syndrome. 24892637 2 20 attach linked 210:215 arg1 diseases 242:249 sex steroid-dependent diseases 220:249 sex steroid-dependent diseases 220:249 Several single nucleotide polymorphisms in the human SHBG gene have been linked to sex steroid-dependent diseases, including those associated with the metabolic syndrome. 24892637 2 20 attach linked 210:215 arg1 those 262:266 those 262:266 those 262:266 Several single nucleotide polymorphisms in the human SHBG gene have been linked to sex steroid-dependent diseases, including those associated with the metabolic syndrome. 24892637 3 21 theme sex 389:391 arg1 steroids 393:400 sex steroids 389:400 sex steroids 389:400 The N-terminal laminin G-like domain of SHBG includes binding sites for calcium, sex steroids, and fibulin family members, as well as a dimerization domain. 24892637 2 22 theme Several 137:143 arg1 polymorphisms 163:175 Several single nucleotide polymorphisms 137:175 Several single nucleotide polymorphisms in the human SHBG gene 137:198 Several single nucleotide polymorphisms in the human SHBG gene have been linked to sex steroid-dependent diseases, including those associated with the metabolic syndrome. 24892637 7 23 contain has 894:896 arg1 R135C 883:887 SHBG R135C 878:887 SHBG R135C 878:887 SHBG R135C also has an increased interaction with fibulin-2. 24892637 7 23 contain has 894:896 arg2 interaction 911:921 an increased interaction 898:921 an increased interaction with fibulin-2 898:936 SHBG R135C also has an increased interaction with fibulin-2. 24892637 5 24 gly glycosylation 672:684 arg1 T7N 715:717 SHBG T7N 710:717 SHBG T7N 710:717 O-Linked glycosylation at Thr7 is disrupted in SHBG T7N, whereas abnormal glycosylation of SHBG G195E limits its secretion. 24892637 5 24 gly glycosylation 672:684 arg1 Thr7 689:692 Thr7 689:692 Thr7 689:692 O-Linked glycosylation at Thr7 is disrupted in SHBG T7N, whereas abnormal glycosylation of SHBG G195E limits its secretion. 24892637 5 24 gly glycosylation 672:684 arg2 Thr7 689:692 Thr7 689:692 Thr7 689:692 O-Linked glycosylation at Thr7 is disrupted in SHBG T7N, whereas abnormal glycosylation of SHBG G195E limits its secretion. 24892637 10 25 theme diseases 1544:1551 arg1 biomarker 1531:1539 a biomarker 1529:1539 a biomarker of diseases 1529:1551 These naturally occurring mutants provide insight into SHBG structure and function, and defects in SHBG production or function need to be considered in the context of its utility as a biomarker of diseases. 24892637 10 25 theme diseases 1544:1551 arg1 defects 1435:1441 defects 1435:1441 defects in SHBG production or function 1435:1472 These naturally occurring mutants provide insight into SHBG structure and function, and defects in SHBG production or function need to be considered in the context of its utility as a biomarker of diseases. 24892637 9 26 theme calcium 1322:1328 arg1 supplementation 1330:1344 calcium supplementation 1322:1344 calcium supplementation 1322:1344 SHBG T48I is defective in calcium binding, which leads to a defect in dimerization, reduced affinity for sex steroids, and an enhanced interaction with fibulin-2, which can all be restored by calcium supplementation. 24892637 4 27 dep production 583:592 arg1 the 579:581 the 579:581 the 579:581 We have found that 8 of 18 uncharacterized nonsynonymous single nucleotide polymorphisms within this domain alter the production or biochemical properties of SHBG in ways not previously recognized. 24892637 7 28 theme increased 901:909 arg1 interaction 911:921 an increased interaction 898:921 an increased interaction with fibulin-2 898:936 SHBG R135C also has an increased interaction with fibulin-2. 24892637 6 29 dep mutants 798:804 arg1 L165M 814:818 L165M 814:818 L165M 814:818 Three SHBG mutants (R135C, L165M, and E176K) bind estradiol with abnormally high affinity. 24892637 6 29 dep mutants 798:804 arg1 E176K 825:829 E176K 825:829 E176K 825:829 Three SHBG mutants (R135C, L165M, and E176K) bind estradiol with abnormally high affinity. 24892637 6 29 dep mutants 798:804 arg1 R135C 807:811 R135C 807:811 R135C 807:811 Three SHBG mutants (R135C, L165M, and E176K) bind estradiol with abnormally high affinity. 24892637 6 29 dep mutants 798:804 arg1 mutants 798:804 Three SHBG mutants 787:804 Three SHBG mutants (R135C, L165M, and E176K) 787:830 Three SHBG mutants (R135C, L165M, and E176K) bind estradiol with abnormally high affinity. 24892637 3 30 theme dimerization 444:455 arg1 domain 457:462 a dimerization domain 442:462 a dimerization domain 442:462 The N-terminal laminin G-like domain of SHBG includes binding sites for calcium, sex steroids, and fibulin family members, as well as a dimerization domain. 24892637 7 31 with interaction 911:921 arg1 fibulin-2 928:936 fibulin-2 928:936 fibulin-2 928:936 SHBG R135C also has an increased interaction with fibulin-2. 24892637 5 32 theme SHBG 710:713 arg1 T7N 715:717 SHBG T7N 710:717 SHBG T7N 710:717 O-Linked glycosylation at Thr7 is disrupted in SHBG T7N, whereas abnormal glycosylation of SHBG G195E limits its secretion. 24892637 2 33 theme SHBG 190:193 arg1 gene 195:198 the human SHBG gene 180:198 the human SHBG gene 180:198 Several single nucleotide polymorphisms in the human SHBG gene have been linked to sex steroid-dependent diseases, including those associated with the metabolic syndrome. 24892637 5 34 gly glycosylation 737:749 arg1 G195E 759:763 SHBG G195E 754:763 SHBG G195E 754:763 O-Linked glycosylation at Thr7 is disrupted in SHBG T7N, whereas abnormal glycosylation of SHBG G195E limits its secretion. 24892637 3 35 theme fibulin 407:413 arg1 members 422:428 fibulin family members 407:428 fibulin family members 407:428 The N-terminal laminin G-like domain of SHBG includes binding sites for calcium, sex steroids, and fibulin family members, as well as a dimerization domain. 24892637 10 36 theme occurring 1363:1371 arg1 mutants 1373:1379 These naturally occurring mutants 1347:1379 These naturally occurring mutants 1347:1379 These naturally occurring mutants provide insight into SHBG structure and function, and defects in SHBG production or function need to be considered in the context of its utility as a biomarker of diseases. 24892637 2 37 theme human 184:188 arg1 gene 195:198 the human SHBG gene 180:198 the human SHBG gene 180:198 Several single nucleotide polymorphisms in the human SHBG gene have been linked to sex steroid-dependent diseases, including those associated with the metabolic syndrome. 24892637 9 38 with dimerization 1200:1211 arg1 fibulin-2 1282:1290 fibulin-2 1282:1290 fibulin-2 1282:1290 SHBG T48I is defective in calcium binding, which leads to a defect in dimerization, reduced affinity for sex steroids, and an enhanced interaction with fibulin-2, which can all be restored by calcium supplementation. 24892637 0 39 theme SHBG 35:38 arg1 structure 40:48 SHBG structure 35:48 SHBG structure 35:48 Naturally occurring mutants inform SHBG structure and function. 24892637 4 40 theme nonsynonymous 508:520 arg1 polymorphisms 540:552 8 of 18 uncharacterized nonsynonymous single nucleotide polymorphisms 484:552 8 of 18 uncharacterized nonsynonymous single nucleotide polymorphisms within this domain 484:571 We have found that 8 of 18 uncharacterized nonsynonymous single nucleotide polymorphisms within this domain alter the production or biochemical properties of SHBG in ways not previously recognized. 24892637 3 41 theme family 415:420 arg1 members 422:428 fibulin family members 407:428 fibulin family members 407:428 The N-terminal laminin G-like domain of SHBG includes binding sites for calcium, sex steroids, and fibulin family members, as well as a dimerization domain. 24892637 2 42 theme steroid-dependent 224:240 arg1 diseases 242:249 sex steroid-dependent diseases 220:249 sex steroid-dependent diseases 220:249 Several single nucleotide polymorphisms in the human SHBG gene have been linked to sex steroid-dependent diseases, including those associated with the metabolic syndrome. 24892637 2 42 theme steroid-dependent 224:240 arg1 those 262:266 those 262:266 those 262:266 Several single nucleotide polymorphisms in the human SHBG gene have been linked to sex steroid-dependent diseases, including those associated with the metabolic syndrome. 24892637 10 43 from defects 1435:1441 arg1 function 1465:1472 function 1465:1472 function 1465:1472 These naturally occurring mutants provide insight into SHBG structure and function, and defects in SHBG production or function need to be considered in the context of its utility as a biomarker of diseases. 24892637 10 43 from defects 1435:1441 arg1 production 1451:1460 SHBG production 1446:1460 SHBG production 1446:1460 These naturally occurring mutants provide insight into SHBG structure and function, and defects in SHBG production or function need to be considered in the context of its utility as a biomarker of diseases. 24892637 2 44 from polymorphisms 163:175 arg1 gene 195:198 the human SHBG gene 180:198 the human SHBG gene 180:198 Several single nucleotide polymorphisms in the human SHBG gene have been linked to sex steroid-dependent diseases, including those associated with the metabolic syndrome. 24892637 4 45 theme uncharacterized 492:506 arg1 polymorphisms 540:552 8 of 18 uncharacterized nonsynonymous single nucleotide polymorphisms 484:552 8 of 18 uncharacterized nonsynonymous single nucleotide polymorphisms within this domain 484:571 We have found that 8 of 18 uncharacterized nonsynonymous single nucleotide polymorphisms within this domain alter the production or biochemical properties of SHBG in ways not previously recognized. 24892637 3 46 theme N-terminal 312:321 arg1 SHBG 348:351 SHBG 348:351 SHBG 348:351 The N-terminal laminin G-like domain of SHBG includes binding sites for calcium, sex steroids, and fibulin family members, as well as a dimerization domain. 24892637 3 46 theme N-terminal 312:321 arg1 domain 338:343 The N-terminal laminin G-like domain 308:343 The N-terminal laminin G-like domain of SHBG 308:351 The N-terminal laminin G-like domain of SHBG includes binding sites for calcium, sex steroids, and fibulin family members, as well as a dimerization domain. 24892637 5 47 theme G195E 759:763 arg1 glycosylation 737:749 abnormal glycosylation 728:749 abnormal glycosylation of SHBG G195E 728:763 O-Linked glycosylation at Thr7 is disrupted in SHBG T7N, whereas abnormal glycosylation of SHBG G195E limits its secretion. 24892637 2 48 theme sex 220:222 arg1 diseases 242:249 sex steroid-dependent diseases 220:249 sex steroid-dependent diseases 220:249 Several single nucleotide polymorphisms in the human SHBG gene have been linked to sex steroid-dependent diseases, including those associated with the metabolic syndrome. 24892637 2 48 theme sex 220:222 arg1 those 262:266 those 262:266 those 262:266 Several single nucleotide polymorphisms in the human SHBG gene have been linked to sex steroid-dependent diseases, including those associated with the metabolic syndrome. 24892637 6 49 theme high 863:866 arg1 affinity 868:875 abnormally high affinity 852:875 abnormally high affinity 852:875 Three SHBG mutants (R135C, L165M, and E176K) bind estradiol with abnormally high affinity. 24892637 1 50 theme androgens 112:120 arg1 activities 98:107 the activities 94:107 the activities of androgens and estrogens 94:134 SHBG transports and regulates the activities of androgens and estrogens. 24892637 10 51 theme SHBG 1446:1449 arg1 production 1451:1460 SHBG production 1446:1460 SHBG production 1446:1460 These naturally occurring mutants provide insight into SHBG structure and function, and defects in SHBG production or function need to be considered in the context of its utility as a biomarker of diseases. 24892637 4 52 theme nucleotide 529:538 arg1 polymorphisms 540:552 8 of 18 uncharacterized nonsynonymous single nucleotide polymorphisms 484:552 8 of 18 uncharacterized nonsynonymous single nucleotide polymorphisms within this domain 484:571 We have found that 8 of 18 uncharacterized nonsynonymous single nucleotide polymorphisms within this domain alter the production or biochemical properties of SHBG in ways not previously recognized. 24892637 3 53 theme laminin 323:329 arg1 SHBG 348:351 SHBG 348:351 SHBG 348:351 The N-terminal laminin G-like domain of SHBG includes binding sites for calcium, sex steroids, and fibulin family members, as well as a dimerization domain. 24892637 3 53 theme laminin 323:329 arg1 domain 338:343 The N-terminal laminin G-like domain 308:343 The N-terminal laminin G-like domain of SHBG 308:351 The N-terminal laminin G-like domain of SHBG includes binding sites for calcium, sex steroids, and fibulin family members, as well as a dimerization domain. 24892637 9 54 from defect 1190:1195 arg1 interaction 1265:1275 an enhanced interaction 1253:1275 an enhanced interaction with fibulin-2 1253:1290 SHBG T48I is defective in calcium binding, which leads to a defect in dimerization, reduced affinity for sex steroids, and an enhanced interaction with fibulin-2, which can all be restored by calcium supplementation. 24892637 9 54 from defect 1190:1195 arg1 affinity 1222:1229 reduced affinity 1214:1229 reduced affinity for sex steroids 1214:1246 SHBG T48I is defective in calcium binding, which leads to a defect in dimerization, reduced affinity for sex steroids, and an enhanced interaction with fibulin-2, which can all be restored by calcium supplementation. 24892637 9 54 from defect 1190:1195 arg1 dimerization 1200:1211 dimerization 1200:1211 dimerization 1200:1211 SHBG T48I is defective in calcium binding, which leads to a defect in dimerization, reduced affinity for sex steroids, and an enhanced interaction with fibulin-2, which can all be restored by calcium supplementation. 24892637 4 55 theme single 522:527 arg1 polymorphisms 540:552 8 of 18 uncharacterized nonsynonymous single nucleotide polymorphisms 484:552 8 of 18 uncharacterized nonsynonymous single nucleotide polymorphisms within this domain 484:571 We have found that 8 of 18 uncharacterized nonsynonymous single nucleotide polymorphisms within this domain alter the production or biochemical properties of SHBG in ways not previously recognized. 24892637 9 56 with interaction 1265:1275 arg1 fibulin-2 1282:1290 fibulin-2 1282:1290 fibulin-2 1282:1290 SHBG T48I is defective in calcium binding, which leads to a defect in dimerization, reduced affinity for sex steroids, and an enhanced interaction with fibulin-2, which can all be restored by calcium supplementation. 24892637 9 57 theme SHBG 1130:1133 arg1 T48I 1135:1138 SHBG T48I 1130:1138 SHBG T48I 1130:1138 SHBG T48I is defective in calcium binding, which leads to a defect in dimerization, reduced affinity for sex steroids, and an enhanced interaction with fibulin-2, which can all be restored by calcium supplementation. 24892637 1 58 theme estrogens 126:134 arg1 activities 98:107 the activities 94:107 the activities of androgens and estrogens 94:134 SHBG transports and regulates the activities of androgens and estrogens. 24892637 8 59 theme binding 1098:1104 arg1 affinity 1106:1113 the relative binding affinity 1085:1113 the relative binding affinity for estradiol 1085:1127 Two different substitutions within the dimer interface at R123 (R123H and R123C) reduce the affinity for 5α-dihydrotestosterone, while increasing the relative binding affinity for estradiol. 24892637 9 60 theme sex 1235:1237 arg1 steroids 1239:1246 sex steroids 1235:1246 sex steroids 1235:1246 SHBG T48I is defective in calcium binding, which leads to a defect in dimerization, reduced affinity for sex steroids, and an enhanced interaction with fibulin-2, which can all be restored by calcium supplementation. 24892637 8 61 from R123 997:1000 arg1 substitutions 953:965 Two different substitutions 939:965 Two different substitutions within the dimer interface at R123 (R123H and R123C) 939:1018 Two different substitutions within the dimer interface at R123 (R123H and R123C) reduce the affinity for 5α-dihydrotestosterone, while increasing the relative binding affinity for estradiol. 24892637 7 62 theme SHBG 878:881 arg1 R135C 883:887 SHBG R135C 878:887 SHBG R135C 878:887 SHBG R135C also has an increased interaction with fibulin-2. 24892637 4 63 theme biochemical 597:607 arg1 properties 609:618 biochemical properties 597:618 biochemical properties 597:618 We have found that 8 of 18 uncharacterized nonsynonymous single nucleotide polymorphisms within this domain alter the production or biochemical properties of SHBG in ways not previously recognized. 24892637 5 64 theme SHBG 754:757 arg1 G195E 759:763 SHBG G195E 754:763 SHBG G195E 754:763 O-Linked glycosylation at Thr7 is disrupted in SHBG T7N, whereas abnormal glycosylation of SHBG G195E limits its secretion. 24892637 10 65 theme utility 1518:1524 arg1 context 1503:1509 the context 1499:1509 the context of its utility 1499:1524 These naturally occurring mutants provide insight into SHBG structure and function, and defects in SHBG production or function need to be considered in the context of its utility as a biomarker of diseases. 24892637 4 66 theme SHBG 623:626 arg1 production 583:592 production 583:592 production 583:592 We have found that 8 of 18 uncharacterized nonsynonymous single nucleotide polymorphisms within this domain alter the production or biochemical properties of SHBG in ways not previously recognized. 24892637 4 66 theme SHBG 623:626 arg1 properties 609:618 biochemical properties 597:618 biochemical properties 597:618 We have found that 8 of 18 uncharacterized nonsynonymous single nucleotide polymorphisms within this domain alter the production or biochemical properties of SHBG in ways not previously recognized. 24892637 3 67 theme SHBG 348:351 arg1 SHBG 348:351 SHBG 348:351 SHBG 348:351 The N-terminal laminin G-like domain of SHBG includes binding sites for calcium, sex steroids, and fibulin family members, as well as a dimerization domain. 24892637 3 67 theme SHBG 348:351 arg1 domain 338:343 The N-terminal laminin G-like domain 308:343 The N-terminal laminin G-like domain of SHBG 308:351 The N-terminal laminin G-like domain of SHBG includes binding sites for calcium, sex steroids, and fibulin family members, as well as a dimerization domain. 24892637 5 68 from Thr7 689:692 arg1 glycosylation 672:684 O-Linked glycosylation 663:684 O-Linked glycosylation at Thr7 663:692 O-Linked glycosylation at Thr7 is disrupted in SHBG T7N, whereas abnormal glycosylation of SHBG G195E limits its secretion. 24892637 8 69 theme different 943:951 arg1 substitutions 953:965 Two different substitutions 939:965 Two different substitutions within the dimer interface at R123 (R123H and R123C) 939:1018 Two different substitutions within the dimer interface at R123 (R123H and R123C) reduce the affinity for 5α-dihydrotestosterone, while increasing the relative binding affinity for estradiol. 24892637 0 70 theme occurring 10:18 arg1 mutants 20:26 Naturally occurring mutants 0:26 Naturally occurring mutants 0:26 Naturally occurring mutants inform SHBG structure and function. 24892637 5 71 theme abnormal 728:735 arg1 glycosylation 737:749 abnormal glycosylation 728:749 abnormal glycosylation of SHBG G195E 728:763 O-Linked glycosylation at Thr7 is disrupted in SHBG T7N, whereas abnormal glycosylation of SHBG G195E limits its secretion. 28791335 2 0 theme rat 436:438 arg1 granulosa 440:448 rat granulosa and Leydig cells 436:465 granulosa 440:448 Previous studies from this laboratory had demonstrated that recombinant eCG (rec-eCG) from Chinese hamster ovary (CHO-K1) cells exhibited both FSH- and LH-like activity in rat granulosa and Leydig cells. 28791335 6 1 theme selected 847:854 arg1 receptor 889:896 the stably selected rat follicle-stimulating hormone receptor 836:896 the stably selected rat follicle-stimulating hormone receptor (rFSHR) 836:904 Internalization values in the stably selected rat follicle-stimulating hormone receptor (rFSHR) and rat luteinizing/chorionic gonadotropin receptor (rLH/CGR) were highest at 50 min after stimulation with 10 ng of rec-eCGβ/α. 28791335 6 1 theme selected 847:854 arg1 rFSHR 899:903 rFSHR 899:903 rFSHR 899:903 Internalization values in the stably selected rat follicle-stimulating hormone receptor (rFSHR) and rat luteinizing/chorionic gonadotropin receptor (rLH/CGR) were highest at 50 min after stimulation with 10 ng of rec-eCGβ/α. 28791335 3 2 from Asn56 624:628 arg1 oligosaccharide 605:619 an N-linked oligosaccharide 593:619 an N-linked oligosaccharide at Asn56 of the α-subunit 593:645 In this study, we analyzed receptor internalization through rec-eCGs, wild type eCG (eCGβ/α) and mutant eCG (eCGβ/αΔ56) with an N-linked oligosaccharide at Asn56 of the α-subunit. 28791335 2 3 theme recombinant 324:334 arg1 rec-eCG 341:347 rec-eCG 341:347 rec-eCG 341:347 Previous studies from this laboratory had demonstrated that recombinant eCG (rec-eCG) from Chinese hamster ovary (CHO-K1) cells exhibited both FSH- and LH-like activity in rat granulosa and Leydig cells. 28791335 2 3 theme recombinant 324:334 arg1 eCG 336:338 recombinant eCG 324:338 recombinant eCG (rec-eCG) from Chinese hamster ovary (CHO-K1) cells 324:390 Previous studies from this laboratory had demonstrated that recombinant eCG (rec-eCG) from Chinese hamster ovary (CHO-K1) cells exhibited both FSH- and LH-like activity in rat granulosa and Leydig cells. 28791335 1 4 theme luteinizing 221:231 arg1 hormone 233:239 luteinizing hormone 221:239 luteinizing hormone (LH) 221:244 Equine chorionic gonadotropin (eCG) is a unique molecule that elicits the response characteristics of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in other species. 28791335 1 4 theme luteinizing 221:231 arg1 LH 242:243 LH 242:243 LH 242:243 Equine chorionic gonadotropin (eCG) is a unique molecule that elicits the response characteristics of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in other species. 28791335 0 5 theme CHO-K1 61:66 arg1 Cells 68:72 CHO-K1 Cells 61:72 CHO-K1 Cells 61:72 Internalization of Rat FSH and LH/CG Receptors by rec-eCG in CHO-K1 Cells. 28791335 3 6 theme N-linked 596:603 arg1 oligosaccharide 605:619 an N-linked oligosaccharide 593:619 an N-linked oligosaccharide at Asn56 of the α-subunit 593:645 In this study, we analyzed receptor internalization through rec-eCGs, wild type eCG (eCGβ/α) and mutant eCG (eCGβ/αΔ56) with an N-linked oligosaccharide at Asn56 of the α-subunit. 28791335 2 7 from laboratory 291:300 arg1 studies 273:279 Previous studies 264:279 Previous studies from this laboratory 264:300 Previous studies from this laboratory had demonstrated that recombinant eCG (rec-eCG) from Chinese hamster ovary (CHO-K1) cells exhibited both FSH- and LH-like activity in rat granulosa and Leydig cells. 28791335 1 8 theme hormone 233:239 arg1 characteristics 158:172 the response characteristics 145:172 the response characteristics of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in other species 145:261 Equine chorionic gonadotropin (eCG) is a unique molecule that elicits the response characteristics of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in other species. 28791335 7 9 theme rec-eCGβ/α 1089:1098 arg1 ng 1083:1084 10 ng 1080:1084 10 ng of rec-eCGβ/α 1080:1098 The dose-dependent response was highest when 10 ng of rec-eCGβ/α was used. 28791335 0 10 from Internalization 0:14 arg1 Cells 68:72 CHO-K1 Cells 61:72 CHO-K1 Cells 61:72 Internalization of Rat FSH and LH/CG Receptors by rec-eCG in CHO-K1 Cells. 28791335 7 11 theme dose-dependent 1039:1052 arg1 response 1054:1061 The dose-dependent response 1035:1061 The dose-dependent response 1035:1061 The dose-dependent response was highest when 10 ng of rec-eCGβ/α was used. 28791335 7 11 theme dose-dependent 1039:1052 arg1 highest 1067:1073 highest 1067:1073 highest 1067:1073 The dose-dependent response was highest when 10 ng of rec-eCGβ/α was used. 28791335 8 12 gly deglycosylated 1114:1127 arg1 mutant 1139:1144 The deglycosylated eCGβ/αΔ56 mutant 1110:1144 The deglycosylated eCGβ/αΔ56 mutant 1110:1144 The deglycosylated eCGβ/αΔ56 mutant did not enhance the agonist-stimulated internalization. 28791335 11 13 theme responsiveness 1476:1489 arg1 lack 1468:1471 the lack 1464:1471 the lack of responsiveness of the deglycosylated eCGβ/ αΔ56 1464:1522 We also suggested that the lack of responsiveness of the deglycosylated eCGβ/ αΔ56 was likely because the site of glycosylation played a pivotal role in agonist-stimulated internalization in cells expressing rFSHR and rLH/CGR. 28791335 11 13 theme responsiveness 1476:1489 arg1 likely 1528:1533 likely 1528:1533 likely 1528:1533 We also suggested that the lack of responsiveness of the deglycosylated eCGβ/ αΔ56 was likely because the site of glycosylation played a pivotal role in agonist-stimulated internalization in cells expressing rFSHR and rLH/CGR. 28791335 6 14 theme gonadotropin 936:947 arg1 receptor 949:956 rat luteinizing/chorionic gonadotropin receptor 910:956 rat luteinizing/chorionic gonadotropin receptor (rLH/CGR) 910:966 Internalization values in the stably selected rat follicle-stimulating hormone receptor (rFSHR) and rat luteinizing/chorionic gonadotropin receptor (rLH/CGR) were highest at 50 min after stimulation with 10 ng of rec-eCGβ/α. 28791335 6 14 theme gonadotropin 936:947 arg1 rLH/CGR 959:965 rLH/CGR 959:965 rLH/CGR 959:965 Internalization values in the stably selected rat follicle-stimulating hormone receptor (rFSHR) and rat luteinizing/chorionic gonadotropin receptor (rLH/CGR) were highest at 50 min after stimulation with 10 ng of rec-eCGβ/α. 28791335 3 15 theme α-subunit 637:645 arg1 Asn56 624:628 Asn56 624:628 Asn56 of the α-subunit 624:645 In this study, we analyzed receptor internalization through rec-eCGs, wild type eCG (eCGβ/α) and mutant eCG (eCGβ/αΔ56) with an N-linked oligosaccharide at Asn56 of the α-subunit. 28791335 6 16 theme luteinizing/chorionic 914:934 arg1 receptor 949:956 rat luteinizing/chorionic gonadotropin receptor 910:956 rat luteinizing/chorionic gonadotropin receptor (rLH/CGR) 910:966 Internalization values in the stably selected rat follicle-stimulating hormone receptor (rFSHR) and rat luteinizing/chorionic gonadotropin receptor (rLH/CGR) were highest at 50 min after stimulation with 10 ng of rec-eCGβ/α. 28791335 6 16 theme luteinizing/chorionic 914:934 arg1 rLH/CGR 959:965 rLH/CGR 959:965 rLH/CGR 959:965 Internalization values in the stably selected rat follicle-stimulating hormone receptor (rFSHR) and rat luteinizing/chorionic gonadotropin receptor (rLH/CGR) were highest at 50 min after stimulation with 10 ng of rec-eCGβ/α. 28791335 11 17 theme deglycosylated 1498:1511 arg1 αΔ56 1519:1522 the deglycosylated eCGβ/ αΔ56 1494:1522 the deglycosylated eCGβ/ αΔ56 1494:1522 We also suggested that the lack of responsiveness of the deglycosylated eCGβ/ αΔ56 was likely because the site of glycosylation played a pivotal role in agonist-stimulated internalization in cells expressing rFSHR and rLH/CGR. 28791335 6 18 theme rec-eCGβ/α 1023:1032 arg1 ng 1017:1018 10 ng 1014:1018 10 ng of rec-eCGβ/α 1014:1032 Internalization values in the stably selected rat follicle-stimulating hormone receptor (rFSHR) and rat luteinizing/chorionic gonadotropin receptor (rLH/CGR) were highest at 50 min after stimulation with 10 ng of rec-eCGβ/α. 28791335 5 19 theme stimulation 761:771 arg1 time 773:776 stimulation time 761:776 stimulation time 761:776 The agonist activation of receptors was analyzed by measuring stimulation time and concentrations of rec-eCGs. 28791335 9 20 theme rLH/CGR 1257:1263 arg1 activation 1233:1242 activation 1233:1242 activation of rFSHR and rLH/CGR 1233:1263 We concluded that the state of activation of rFSHR and rLH/CGR could be modulated through agonist-stimulated internalization. 28791335 11 21 theme eCGβ/ 1513:1517 arg1 αΔ56 1519:1522 the deglycosylated eCGβ/ αΔ56 1494:1522 the deglycosylated eCGβ/ αΔ56 1494:1522 We also suggested that the lack of responsiveness of the deglycosylated eCGβ/ αΔ56 was likely because the site of glycosylation played a pivotal role in agonist-stimulated internalization in cells expressing rFSHR and rLH/CGR. 28791335 2 22 theme Chinese 355:361 arg1 cells 386:390 Chinese hamster ovary (CHO-K1) cells 355:390 Chinese hamster ovary (CHO-K1) cells 355:390 Previous studies from this laboratory had demonstrated that recombinant eCG (rec-eCG) from Chinese hamster ovary (CHO-K1) cells exhibited both FSH- and LH-like activity in rat granulosa and Leydig cells. 28791335 2 23 theme Leydig 454:459 arg1 cells 461:465 rat granulosa and Leydig cells 436:465 cells 461:465 Previous studies from this laboratory had demonstrated that recombinant eCG (rec-eCG) from Chinese hamster ovary (CHO-K1) cells exhibited both FSH- and LH-like activity in rat granulosa and Leydig cells. 28791335 2 24 from activity 424:431 arg1 granulosa 440:448 rat granulosa and Leydig cells 436:465 granulosa 440:448 Previous studies from this laboratory had demonstrated that recombinant eCG (rec-eCG) from Chinese hamster ovary (CHO-K1) cells exhibited both FSH- and LH-like activity in rat granulosa and Leydig cells. 28791335 2 24 from activity 424:431 arg1 cells 461:465 rat granulosa and Leydig cells 436:465 cells 461:465 Previous studies from this laboratory had demonstrated that recombinant eCG (rec-eCG) from Chinese hamster ovary (CHO-K1) cells exhibited both FSH- and LH-like activity in rat granulosa and Leydig cells. 28791335 6 25 from values 826:831 arg1 receptor 949:956 rat luteinizing/chorionic gonadotropin receptor 910:956 rat luteinizing/chorionic gonadotropin receptor (rLH/CGR) 910:966 Internalization values in the stably selected rat follicle-stimulating hormone receptor (rFSHR) and rat luteinizing/chorionic gonadotropin receptor (rLH/CGR) were highest at 50 min after stimulation with 10 ng of rec-eCGβ/α. 28791335 6 25 from values 826:831 arg1 receptor 889:896 the stably selected rat follicle-stimulating hormone receptor 836:896 the stably selected rat follicle-stimulating hormone receptor (rFSHR) 836:904 Internalization values in the stably selected rat follicle-stimulating hormone receptor (rFSHR) and rat luteinizing/chorionic gonadotropin receptor (rLH/CGR) were highest at 50 min after stimulation with 10 ng of rec-eCGβ/α. 28791335 6 25 from values 826:831 arg1 rFSHR 899:903 rFSHR 899:903 rFSHR 899:903 Internalization values in the stably selected rat follicle-stimulating hormone receptor (rFSHR) and rat luteinizing/chorionic gonadotropin receptor (rLH/CGR) were highest at 50 min after stimulation with 10 ng of rec-eCGβ/α. 28791335 6 25 from values 826:831 arg1 rLH/CGR 959:965 rLH/CGR 959:965 rLH/CGR 959:965 Internalization values in the stably selected rat follicle-stimulating hormone receptor (rFSHR) and rat luteinizing/chorionic gonadotropin receptor (rLH/CGR) were highest at 50 min after stimulation with 10 ng of rec-eCGβ/α. 28791335 4 26 theme CHO-K1 685:690 arg1 cells 692:696 CHO-K1 cells 685:696 CHO-K1 cells 685:696 Both the rec-eCGs were obtained from CHO-K1 cells. 28791335 8 27 theme agonist-stimulated 1166:1183 arg1 internalization 1185:1199 the agonist-stimulated internalization 1162:1199 the agonist-stimulated internalization 1162:1199 The deglycosylated eCGβ/αΔ56 mutant did not enhance the agonist-stimulated internalization. 28791335 8 28 theme deglycosylated 1114:1127 arg1 mutant 1139:1144 The deglycosylated eCGβ/αΔ56 mutant 1110:1144 The deglycosylated eCGβ/αΔ56 mutant 1110:1144 The deglycosylated eCGβ/αΔ56 mutant did not enhance the agonist-stimulated internalization. 28791335 11 29 theme agonist-stimulated 1594:1611 arg1 internalization 1613:1627 agonist-stimulated internalization 1594:1627 agonist-stimulated internalization in cells expressing rFSHR and rLH/CGR 1594:1665 We also suggested that the lack of responsiveness of the deglycosylated eCGβ/ αΔ56 was likely because the site of glycosylation played a pivotal role in agonist-stimulated internalization in cells expressing rFSHR and rLH/CGR. 28791335 11 30 theme glycosylation 1555:1567 arg1 glycosylation 1555:1567 glycosylation 1555:1567 glycosylation 1555:1567 We also suggested that the lack of responsiveness of the deglycosylated eCGβ/ αΔ56 was likely because the site of glycosylation played a pivotal role in agonist-stimulated internalization in cells expressing rFSHR and rLH/CGR. 28791335 11 30 theme glycosylation 1555:1567 arg1 site 1547:1550 the site 1543:1550 the site of glycosylation 1543:1567 We also suggested that the lack of responsiveness of the deglycosylated eCGβ/ αΔ56 was likely because the site of glycosylation played a pivotal role in agonist-stimulated internalization in cells expressing rFSHR and rLH/CGR. 28791335 1 31 theme response 149:156 arg1 characteristics 158:172 the response characteristics 145:172 the response characteristics of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in other species 145:261 Equine chorionic gonadotropin (eCG) is a unique molecule that elicits the response characteristics of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in other species. 28791335 5 32 theme receptors 725:733 arg1 activation 711:720 The agonist activation 699:720 The agonist activation of receptors 699:733 The agonist activation of receptors was analyzed by measuring stimulation time and concentrations of rec-eCGs. 28791335 6 33 theme rat 910:912 arg1 receptor 949:956 rat luteinizing/chorionic gonadotropin receptor 910:956 rat luteinizing/chorionic gonadotropin receptor (rLH/CGR) 910:966 Internalization values in the stably selected rat follicle-stimulating hormone receptor (rFSHR) and rat luteinizing/chorionic gonadotropin receptor (rLH/CGR) were highest at 50 min after stimulation with 10 ng of rec-eCGβ/α. 28791335 6 33 theme rat 910:912 arg1 rLH/CGR 959:965 rLH/CGR 959:965 rLH/CGR 959:965 Internalization values in the stably selected rat follicle-stimulating hormone receptor (rFSHR) and rat luteinizing/chorionic gonadotropin receptor (rLH/CGR) were highest at 50 min after stimulation with 10 ng of rec-eCGβ/α. 28791335 1 34 theme Equine 75:80 arg1 molecule 123:130 a unique molecule 114:130 a unique molecule that elicits the response characteristics of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in other species 114:261 Equine chorionic gonadotropin (eCG) is a unique molecule that elicits the response characteristics of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in other species. 28791335 1 34 theme Equine 75:80 arg1 eCG 106:108 eCG 106:108 eCG 106:108 Equine chorionic gonadotropin (eCG) is a unique molecule that elicits the response characteristics of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in other species. 28791335 1 34 theme Equine 75:80 arg1 gonadotropin 92:103 Equine chorionic gonadotropin 75:103 Equine chorionic gonadotropin (eCG) 75:109 Equine chorionic gonadotropin (eCG) is a unique molecule that elicits the response characteristics of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in other species. 28791335 0 35 theme Receptors 37:45 arg1 Internalization 0:14 Internalization 0:14 Internalization of Rat FSH and LH/CG Receptors by rec-eCG in CHO-K1 Cells 0:72 Internalization of Rat FSH and LH/CG Receptors by rec-eCG in CHO-K1 Cells. 28791335 5 36 theme rec-eCGs 800:807 arg1 concentrations 782:795 concentrations 782:795 concentrations of rec-eCGs 782:807 The agonist activation of receptors was analyzed by measuring stimulation time and concentrations of rec-eCGs. 28791335 5 36 theme rec-eCGs 800:807 arg1 time 773:776 stimulation time 761:776 stimulation time 761:776 The agonist activation of receptors was analyzed by measuring stimulation time and concentrations of rec-eCGs. 28791335 0 37 theme FSH 23:25 arg1 Internalization 0:14 Internalization 0:14 Internalization of Rat FSH and LH/CG Receptors by rec-eCG in CHO-K1 Cells 0:72 Internalization of Rat FSH and LH/CG Receptors by rec-eCG in CHO-K1 Cells. 28791335 1 38 theme chorionic 82:90 arg1 molecule 123:130 a unique molecule 114:130 a unique molecule that elicits the response characteristics of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in other species 114:261 Equine chorionic gonadotropin (eCG) is a unique molecule that elicits the response characteristics of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in other species. 28791335 1 38 theme chorionic 82:90 arg1 eCG 106:108 eCG 106:108 eCG 106:108 Equine chorionic gonadotropin (eCG) is a unique molecule that elicits the response characteristics of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in other species. 28791335 1 38 theme chorionic 82:90 arg1 gonadotropin 92:103 Equine chorionic gonadotropin 75:103 Equine chorionic gonadotropin (eCG) 75:109 Equine chorionic gonadotropin (eCG) is a unique molecule that elicits the response characteristics of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in other species. 28791335 11 39 theme αΔ56 1519:1522 arg1 responsiveness 1476:1489 responsiveness 1476:1489 responsiveness of the deglycosylated eCGβ/ αΔ56 1476:1522 We also suggested that the lack of responsiveness of the deglycosylated eCGβ/ αΔ56 was likely because the site of glycosylation played a pivotal role in agonist-stimulated internalization in cells expressing rFSHR and rLH/CGR. 28791335 2 40 theme CHO-K1 378:383 arg1 cells 386:390 Chinese hamster ovary (CHO-K1) cells 355:390 Chinese hamster ovary (CHO-K1) cells 355:390 Previous studies from this laboratory had demonstrated that recombinant eCG (rec-eCG) from Chinese hamster ovary (CHO-K1) cells exhibited both FSH- and LH-like activity in rat granulosa and Leydig cells. 28791335 0 41 theme Rat 19:21 arg1 FSH 23:25 Rat FSH 19:25 Rat FSH 19:25 Internalization of Rat FSH and LH/CG Receptors by rec-eCG in CHO-K1 Cells. 28791335 1 42 theme other 249:253 arg1 species 255:261 other species 249:261 other species 249:261 Equine chorionic gonadotropin (eCG) is a unique molecule that elicits the response characteristics of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in other species. 28791335 3 43 theme receptor 495:502 arg1 internalization 504:518 receptor internalization 495:518 receptor internalization 495:518 In this study, we analyzed receptor internalization through rec-eCGs, wild type eCG (eCGβ/α) and mutant eCG (eCGβ/αΔ56) with an N-linked oligosaccharide at Asn56 of the α-subunit. 28791335 3 44 with eCG 572:574 arg1 oligosaccharide 605:619 an N-linked oligosaccharide 593:619 an N-linked oligosaccharide at Asn56 of the α-subunit 593:645 In this study, we analyzed receptor internalization through rec-eCGs, wild type eCG (eCGβ/α) and mutant eCG (eCGβ/αΔ56) with an N-linked oligosaccharide at Asn56 of the α-subunit. 28791335 3 45 link N-linked 596:603 arg1 oligosaccharide 605:619 an N-linked oligosaccharide 593:619 an N-linked oligosaccharide at Asn56 of the α-subunit 593:645 In this study, we analyzed receptor internalization through rec-eCGs, wild type eCG (eCGβ/α) and mutant eCG (eCGβ/αΔ56) with an N-linked oligosaccharide at Asn56 of the α-subunit. 28791335 0 46 theme LH/CG 31:35 arg1 Receptors 37:45 LH/CG Receptors 31:45 LH/CG Receptors 31:45 Internalization of Rat FSH and LH/CG Receptors by rec-eCG in CHO-K1 Cells. 28791335 1 47 theme follicle-stimulating 182:201 arg1 FSH 212:214 FSH 212:214 FSH 212:214 Equine chorionic gonadotropin (eCG) is a unique molecule that elicits the response characteristics of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in other species. 28791335 1 47 theme follicle-stimulating 182:201 arg1 hormone 203:209 follicle-stimulating hormone 182:209 follicle-stimulating hormone (FSH) 182:215 Equine chorionic gonadotropin (eCG) is a unique molecule that elicits the response characteristics of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in other species. 28791335 3 48 theme wild 538:541 arg1 rec-eCGs 528:535 rec-eCGs 528:535 rec-eCGs 528:535 In this study, we analyzed receptor internalization through rec-eCGs, wild type eCG (eCGβ/α) and mutant eCG (eCGβ/αΔ56) with an N-linked oligosaccharide at Asn56 of the α-subunit. 28791335 3 48 theme wild 538:541 arg1 eCGβ/α 553:558 eCGβ/α 553:558 eCGβ/α 553:558 In this study, we analyzed receptor internalization through rec-eCGs, wild type eCG (eCGβ/α) and mutant eCG (eCGβ/αΔ56) with an N-linked oligosaccharide at Asn56 of the α-subunit. 28791335 3 48 theme wild 538:541 arg1 eCG 548:550 wild type eCG 538:550 wild type eCG (eCGβ/α) 538:559 In this study, we analyzed receptor internalization through rec-eCGs, wild type eCG (eCGβ/α) and mutant eCG (eCGβ/αΔ56) with an N-linked oligosaccharide at Asn56 of the α-subunit. 28791335 2 49 theme ovary 371:375 arg1 cells 386:390 Chinese hamster ovary (CHO-K1) cells 355:390 Chinese hamster ovary (CHO-K1) cells 355:390 Previous studies from this laboratory had demonstrated that recombinant eCG (rec-eCG) from Chinese hamster ovary (CHO-K1) cells exhibited both FSH- and LH-like activity in rat granulosa and Leydig cells. 28791335 2 50 theme LH-like 416:422 arg1 activity 424:431 both FSH- and LH-like activity 402:431 both FSH- and LH-like activity in rat granulosa and Leydig cells 402:465 Previous studies from this laboratory had demonstrated that recombinant eCG (rec-eCG) from Chinese hamster ovary (CHO-K1) cells exhibited both FSH- and LH-like activity in rat granulosa and Leydig cells. 28791335 7 51 used used 1104:1107 arg2 ng 1083:1084 10 ng 1080:1084 10 ng of rec-eCGβ/α 1080:1098 The dose-dependent response was highest when 10 ng of rec-eCGβ/α was used. 28791335 3 52 theme type 543:546 arg1 rec-eCGs 528:535 rec-eCGs 528:535 rec-eCGs 528:535 In this study, we analyzed receptor internalization through rec-eCGs, wild type eCG (eCGβ/α) and mutant eCG (eCGβ/αΔ56) with an N-linked oligosaccharide at Asn56 of the α-subunit. 28791335 3 52 theme type 543:546 arg1 eCGβ/α 553:558 eCGβ/α 553:558 eCGβ/α 553:558 In this study, we analyzed receptor internalization through rec-eCGs, wild type eCG (eCGβ/α) and mutant eCG (eCGβ/αΔ56) with an N-linked oligosaccharide at Asn56 of the α-subunit. 28791335 3 52 theme type 543:546 arg1 eCG 548:550 wild type eCG 538:550 wild type eCG (eCGβ/α) 538:559 In this study, we analyzed receptor internalization through rec-eCGs, wild type eCG (eCGβ/α) and mutant eCG (eCGβ/αΔ56) with an N-linked oligosaccharide at Asn56 of the α-subunit. 28791335 6 53 with stimulation 997:1007 arg1 ng 1017:1018 10 ng 1014:1018 10 ng of rec-eCGβ/α 1014:1032 Internalization values in the stably selected rat follicle-stimulating hormone receptor (rFSHR) and rat luteinizing/chorionic gonadotropin receptor (rLH/CGR) were highest at 50 min after stimulation with 10 ng of rec-eCGβ/α. 28791335 1 54 theme hormone 203:209 arg1 characteristics 158:172 the response characteristics 145:172 the response characteristics of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in other species 145:261 Equine chorionic gonadotropin (eCG) is a unique molecule that elicits the response characteristics of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in other species. 28791335 5 55 theme agonist 703:709 arg1 activation 711:720 The agonist activation 699:720 The agonist activation of receptors 699:733 The agonist activation of receptors was analyzed by measuring stimulation time and concentrations of rec-eCGs. 28791335 3 56 theme mutant 565:570 arg1 eCG 572:574 mutant eCG 565:574 mutant eCG (eCGβ/αΔ56) 565:586 In this study, we analyzed receptor internalization through rec-eCGs, wild type eCG (eCGβ/α) and mutant eCG (eCGβ/αΔ56) with an N-linked oligosaccharide at Asn56 of the α-subunit. 28791335 3 56 theme mutant 565:570 arg1 rec-eCGs 528:535 rec-eCGs 528:535 rec-eCGs 528:535 In this study, we analyzed receptor internalization through rec-eCGs, wild type eCG (eCGβ/α) and mutant eCG (eCGβ/αΔ56) with an N-linked oligosaccharide at Asn56 of the α-subunit. 28791335 3 56 theme mutant 565:570 arg1 eCGβ/αΔ56 577:585 eCGβ/αΔ56 577:585 eCGβ/αΔ56 577:585 In this study, we analyzed receptor internalization through rec-eCGs, wild type eCG (eCGβ/α) and mutant eCG (eCGβ/αΔ56) with an N-linked oligosaccharide at Asn56 of the α-subunit. 28791335 6 57 theme Internalization 810:824 arg1 values 826:831 Internalization values 810:831 Internalization values in the stably selected rat follicle-stimulating hormone receptor (rFSHR) and rat luteinizing/chorionic gonadotropin receptor (rLH/CGR) 810:966 Internalization values in the stably selected rat follicle-stimulating hormone receptor (rFSHR) and rat luteinizing/chorionic gonadotropin receptor (rLH/CGR) were highest at 50 min after stimulation with 10 ng of rec-eCGβ/α. 28791335 2 58 theme FSH- 407:410 arg1 activity 424:431 both FSH- and LH-like activity 402:431 both FSH- and LH-like activity in rat granulosa and Leydig cells 402:465 Previous studies from this laboratory had demonstrated that recombinant eCG (rec-eCG) from Chinese hamster ovary (CHO-K1) cells exhibited both FSH- and LH-like activity in rat granulosa and Leydig cells. 28791335 6 59 theme hormone 881:887 arg1 receptor 889:896 the stably selected rat follicle-stimulating hormone receptor 836:896 the stably selected rat follicle-stimulating hormone receptor (rFSHR) 836:904 Internalization values in the stably selected rat follicle-stimulating hormone receptor (rFSHR) and rat luteinizing/chorionic gonadotropin receptor (rLH/CGR) were highest at 50 min after stimulation with 10 ng of rec-eCGβ/α. 28791335 6 59 theme hormone 881:887 arg1 rFSHR 899:903 rFSHR 899:903 rFSHR 899:903 Internalization values in the stably selected rat follicle-stimulating hormone receptor (rFSHR) and rat luteinizing/chorionic gonadotropin receptor (rLH/CGR) were highest at 50 min after stimulation with 10 ng of rec-eCGβ/α. 28791335 6 60 theme rat 856:858 arg1 receptor 889:896 the stably selected rat follicle-stimulating hormone receptor 836:896 the stably selected rat follicle-stimulating hormone receptor (rFSHR) 836:904 Internalization values in the stably selected rat follicle-stimulating hormone receptor (rFSHR) and rat luteinizing/chorionic gonadotropin receptor (rLH/CGR) were highest at 50 min after stimulation with 10 ng of rec-eCGβ/α. 28791335 6 60 theme rat 856:858 arg1 rFSHR 899:903 rFSHR 899:903 rFSHR 899:903 Internalization values in the stably selected rat follicle-stimulating hormone receptor (rFSHR) and rat luteinizing/chorionic gonadotropin receptor (rLH/CGR) were highest at 50 min after stimulation with 10 ng of rec-eCGβ/α. 28791335 9 61 theme activation 1233:1242 arg1 state 1224:1228 the state 1220:1228 the state of activation of rFSHR and rLH/CGR 1220:1263 We concluded that the state of activation of rFSHR and rLH/CGR could be modulated through agonist-stimulated internalization. 28791335 6 62 theme follicle-stimulating 860:879 arg1 receptor 889:896 the stably selected rat follicle-stimulating hormone receptor 836:896 the stably selected rat follicle-stimulating hormone receptor (rFSHR) 836:904 Internalization values in the stably selected rat follicle-stimulating hormone receptor (rFSHR) and rat luteinizing/chorionic gonadotropin receptor (rLH/CGR) were highest at 50 min after stimulation with 10 ng of rec-eCGβ/α. 28791335 6 62 theme follicle-stimulating 860:879 arg1 rFSHR 899:903 rFSHR 899:903 rFSHR 899:903 Internalization values in the stably selected rat follicle-stimulating hormone receptor (rFSHR) and rat luteinizing/chorionic gonadotropin receptor (rLH/CGR) were highest at 50 min after stimulation with 10 ng of rec-eCGβ/α. 28791335 11 63 from internalization 1613:1627 arg1 cells 1632:1636 cells 1632:1636 cells expressing rFSHR and rLH/CGR 1632:1665 We also suggested that the lack of responsiveness of the deglycosylated eCGβ/ αΔ56 was likely because the site of glycosylation played a pivotal role in agonist-stimulated internalization in cells expressing rFSHR and rLH/CGR. 28791335 11 64 gly deglycosylated 1498:1511 arg1 αΔ56 1519:1522 the deglycosylated eCGβ/ αΔ56 1494:1522 the deglycosylated eCGβ/ αΔ56 1494:1522 We also suggested that the lack of responsiveness of the deglycosylated eCGβ/ αΔ56 was likely because the site of glycosylation played a pivotal role in agonist-stimulated internalization in cells expressing rFSHR and rLH/CGR. 28791335 9 65 theme agonist-stimulated 1292:1309 arg1 internalization 1311:1325 agonist-stimulated internalization 1292:1325 agonist-stimulated internalization 1292:1325 We concluded that the state of activation of rFSHR and rLH/CGR could be modulated through agonist-stimulated internalization. 28791335 2 66 theme Previous 264:271 arg1 studies 273:279 Previous studies 264:279 Previous studies from this laboratory 264:300 Previous studies from this laboratory had demonstrated that recombinant eCG (rec-eCG) from Chinese hamster ovary (CHO-K1) cells exhibited both FSH- and LH-like activity in rat granulosa and Leydig cells. 28791335 9 67 theme rFSHR 1247:1251 arg1 activation 1233:1242 activation 1233:1242 activation of rFSHR and rLH/CGR 1233:1263 We concluded that the state of activation of rFSHR and rLH/CGR could be modulated through agonist-stimulated internalization. 28791335 3 68 with eCG 548:550 arg1 oligosaccharide 605:619 an N-linked oligosaccharide 593:619 an N-linked oligosaccharide at Asn56 of the α-subunit 593:645 In this study, we analyzed receptor internalization through rec-eCGs, wild type eCG (eCGβ/α) and mutant eCG (eCGβ/αΔ56) with an N-linked oligosaccharide at Asn56 of the α-subunit. 28791335 2 69 theme hamster 363:369 arg1 cells 386:390 Chinese hamster ovary (CHO-K1) cells 355:390 Chinese hamster ovary (CHO-K1) cells 355:390 Previous studies from this laboratory had demonstrated that recombinant eCG (rec-eCG) from Chinese hamster ovary (CHO-K1) cells exhibited both FSH- and LH-like activity in rat granulosa and Leydig cells. 28791335 1 70 from characteristics 158:172 arg1 species 255:261 other species 249:261 other species 249:261 Equine chorionic gonadotropin (eCG) is a unique molecule that elicits the response characteristics of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in other species. 28791335 11 71 gly glycosylation 1555:1567 arg2 site 1547:1550 the site 1543:1550 the site of glycosylation 1543:1567 We also suggested that the lack of responsiveness of the deglycosylated eCGβ/ αΔ56 was likely because the site of glycosylation played a pivotal role in agonist-stimulated internalization in cells expressing rFSHR and rLH/CGR. 28791335 11 71 gly glycosylation 1555:1567 arg2 glycosylation 1555:1567 glycosylation 1555:1567 glycosylation 1555:1567 We also suggested that the lack of responsiveness of the deglycosylated eCGβ/ αΔ56 was likely because the site of glycosylation played a pivotal role in agonist-stimulated internalization in cells expressing rFSHR and rLH/CGR. 28791335 2 72 from cells 386:390 arg1 rec-eCG 341:347 rec-eCG 341:347 rec-eCG 341:347 Previous studies from this laboratory had demonstrated that recombinant eCG (rec-eCG) from Chinese hamster ovary (CHO-K1) cells exhibited both FSH- and LH-like activity in rat granulosa and Leydig cells. 28791335 2 72 from cells 386:390 arg1 eCG 336:338 recombinant eCG 324:338 recombinant eCG (rec-eCG) from Chinese hamster ovary (CHO-K1) cells 324:390 Previous studies from this laboratory had demonstrated that recombinant eCG (rec-eCG) from Chinese hamster ovary (CHO-K1) cells exhibited both FSH- and LH-like activity in rat granulosa and Leydig cells. 28791335 8 73 theme eCGβ/αΔ56 1129:1137 arg1 mutant 1139:1144 The deglycosylated eCGβ/αΔ56 mutant 1110:1144 The deglycosylated eCGβ/αΔ56 mutant 1110:1144 The deglycosylated eCGβ/αΔ56 mutant did not enhance the agonist-stimulated internalization. 28791335 11 74 theme pivotal 1578:1584 arg1 role 1586:1589 a pivotal role 1576:1589 a pivotal role 1576:1589 We also suggested that the lack of responsiveness of the deglycosylated eCGβ/ αΔ56 was likely because the site of glycosylation played a pivotal role in agonist-stimulated internalization in cells expressing rFSHR and rLH/CGR. 28791335 1 75 theme unique 116:121 arg1 molecule 123:130 a unique molecule 114:130 a unique molecule that elicits the response characteristics of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in other species 114:261 Equine chorionic gonadotropin (eCG) is a unique molecule that elicits the response characteristics of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in other species. 28791335 1 75 theme unique 116:121 arg1 gonadotropin 92:103 Equine chorionic gonadotropin 75:103 Equine chorionic gonadotropin (eCG) 75:109 Equine chorionic gonadotropin (eCG) is a unique molecule that elicits the response characteristics of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in other species. 25828812 8 0 theme immunized 907:915 arg1 mice 917:920 immunized mice 907:920 immunized mice 907:920 The expression levels of IL-4 and IFN-γ in splenocytes of immunized mice and infected mice were detected by ELISA and flow cytometry. 25828812 11 1 theme mice 1325:1328 arg1 sera 1297:1300 sera 1297:1300 sera of CsRNASET2 immunized mice 1297:1328 In addition, sera of CsRNASET2 immunized mice had obviously higher levels of specific antibody titers. 25828812 3 2 theme immune 465:470 arg1 response 472:479 adaptive immune response 456:479 adaptive immune response 456:479 However, it is unclear whether CsRNASET2 can induce adaptive immune response. 25828812 10 3 theme active 1149:1154 arg1 residues 1166:1173 active histidine residues 1149:1173 active histidine residues 1149:1173 The conserved active site (CAS) motifs, active histidine residues, and N-linked glycosylation region of CsRNASET2 were close to each other in the three-dimensional structure. 25828812 10 3 theme active 1149:1154 arg1 CsRNASET2 1213:1221 CsRNASET2 1213:1221 CsRNASET2 1213:1221 The conserved active site (CAS) motifs, active histidine residues, and N-linked glycosylation region of CsRNASET2 were close to each other in the three-dimensional structure. 25828812 12 4 theme CsRNASET2 1409:1417 arg1 mice 1429:1432 CsRNASET2 immunized mice 1409:1432 CsRNASET2 immunized mice 1409:1432 Splenocytes from both CsRNASET2 immunized mice and C. sinensis infected mice expressed increased levels of IL-4, while the production of IFN-γ exhibited no significant difference. 25828812 11 5 theme specific 1361:1368 arg1 titers 1379:1384 specific antibody titers 1361:1384 specific antibody titers 1361:1384 In addition, sera of CsRNASET2 immunized mice had obviously higher levels of specific antibody titers. 25828812 2 6 theme sinensis 280:287 arg1 ESPs 261:264 ESPs 261:264 ESPs of Clonorchis sinensis (C. sinensis, Cs) 261:305 CsRNASET2, a glycosylated T2 ribonuclease present in ESPs of Clonorchis sinensis (C. sinensis, Cs), has recently been reported to possess potent effects in regulating mouse dendritic cells (DCs). 25828812 8 7 theme mice 935:938 arg1 splenocytes 892:902 splenocytes 892:902 splenocytes of immunized mice and infected mice 892:938 The expression levels of IL-4 and IFN-γ in splenocytes of immunized mice and infected mice were detected by ELISA and flow cytometry. 25828812 6 8 theme specific 742:749 arg1 titers 760:765 specific antibody titers 742:765 specific antibody titers 742:765 Sera of immunized mice were collected and evaluated for specific antibody titers by ELISA. 25828812 7 9 theme mice 805:808 arg1 Splenocytes 777:787 Splenocytes 777:787 Splenocytes of experimental mice 777:808 Splenocytes of experimental mice were isolated and stimulated in vitro. 25828812 1 10 theme excretory/secretory 171:189 arg1 proteins 191:198 excretory/secretory proteins 171:198 excretory/secretory proteins (ESPs) 171:205 Many parasites can trigger the host immune response by releasing excretory/secretory proteins (ESPs). 25828812 1 10 theme excretory/secretory 171:189 arg1 ESPs 201:204 ESPs 201:204 ESPs 201:204 Many parasites can trigger the host immune response by releasing excretory/secretory proteins (ESPs). 25828812 13 11 theme C. 1722:1723 arg1 sinensis 1725:1732 C. sinensis 1722:1732 C. sinensis 1722:1732 Immunization with CsRNASET2 elicited Th2 immune response by promoting the synthesis of IL-4, consistent with the immune response initiated by infection of C. sinensis. 25828812 5 12 theme Balb/c 595:600 arg1 mice 602:605 Balb/c mice 595:605 Balb/c mice 595:605 Besides, we immunized Balb/c mice with CsRNASET2 and orally infected Balb/c mice with C. sinensis, respectively. 25828812 12 13 from mice 1459:1462 arg1 Splenocytes 1387:1397 Splenocytes 1387:1397 Splenocytes from both CsRNASET2 immunized mice and C. sinensis infected mice 1387:1462 Splenocytes from both CsRNASET2 immunized mice and C. sinensis infected mice expressed increased levels of IL-4, while the production of IFN-γ exhibited no significant difference. 25828812 5 14 theme C. 659:660 arg1 sinensis 662:669 C. sinensis 659:669 C. sinensis 659:669 Besides, we immunized Balb/c mice with CsRNASET2 and orally infected Balb/c mice with C. sinensis, respectively. 25828812 4 15 contain carried 500:506 arg2 investigations 520:533 further investigations 512:533 further investigations 512:533 In this study, we carried out further investigations on biochemical features of CsRNASET2. 25828812 4 15 contain carried 500:506 arg3 study 490:494 this study 485:494 this study 485:494 In this study, we carried out further investigations on biochemical features of CsRNASET2. 25828812 4 15 contain carried 500:506 arg3 features 550:557 biochemical features 538:557 biochemical features of CsRNASET2 538:570 In this study, we carried out further investigations on biochemical features of CsRNASET2. 25828812 4 15 contain carried 500:506 arg1 we 497:498 we 497:498 we 497:498 In this study, we carried out further investigations on biochemical features of CsRNASET2. 25828812 8 16 theme expression 853:862 arg1 levels 864:869 The expression levels 849:869 The expression levels of IL-4 and IFN-γ in splenocytes of immunized mice and infected mice 849:938 The expression levels of IL-4 and IFN-γ in splenocytes of immunized mice and infected mice were detected by ELISA and flow cytometry. 25828812 11 17 theme CsRNASET2 1305:1313 arg1 mice 1325:1328 CsRNASET2 immunized mice 1305:1328 CsRNASET2 immunized mice 1305:1328 In addition, sera of CsRNASET2 immunized mice had obviously higher levels of specific antibody titers. 25828812 2 18 theme glycosylated 221:232 arg1 ribonuclease 237:248 a glycosylated T2 ribonuclease 219:248 a glycosylated T2 ribonuclease present in ESPs of Clonorchis sinensis (C. sinensis, Cs) 219:305 CsRNASET2, a glycosylated T2 ribonuclease present in ESPs of Clonorchis sinensis (C. sinensis, Cs), has recently been reported to possess potent effects in regulating mouse dendritic cells (DCs). 25828812 2 18 theme glycosylated 221:232 arg1 CsRNASET2 208:216 CsRNASET2 208:216 CsRNASET2 208:216 CsRNASET2, a glycosylated T2 ribonuclease present in ESPs of Clonorchis sinensis (C. sinensis, Cs), has recently been reported to possess potent effects in regulating mouse dendritic cells (DCs). 25828812 14 19 theme immune 1832:1837 arg1 response 1839:1846 Th2 immune response 1828:1846 Th2 immune response 1828:1846 Taken together, these data suggested that CsRNASET2 was important for C. sinensis to trigger Th2 immune response. 25828812 12 20 theme IFN-γ 1524:1528 arg1 production 1510:1519 the production 1506:1519 the production of IFN-γ 1506:1528 Splenocytes from both CsRNASET2 immunized mice and C. sinensis infected mice expressed increased levels of IL-4, while the production of IFN-γ exhibited no significant difference. 25828812 2 21 dep sinensis 293:300 arg1 Cs 303:304 Cs 303:304 Cs 303:304 CsRNASET2, a glycosylated T2 ribonuclease present in ESPs of Clonorchis sinensis (C. sinensis, Cs), has recently been reported to possess potent effects in regulating mouse dendritic cells (DCs). 25828812 0 22 theme responsible 59:69 arg1 CsRNASET2 0:8 CsRNASET2 0:8 CsRNASET2 0:8 CsRNASET2 is an important component of Clonorchis sinensis responsible for eliciting Th2 immune response. 25828812 0 22 theme responsible 59:69 arg1 component 26:34 an important component 13:34 an important component of Clonorchis sinensis responsible for eliciting Th2 immune response 13:103 CsRNASET2 is an important component of Clonorchis sinensis responsible for eliciting Th2 immune response. 25828812 9 23 contain had 1033:1035 arg1 sequence 1011:1018 the sequence 1007:1018 the sequence of CsRNASET2 1007:1031 Our results showed that the sequence of CsRNASET2 had close relationship with the homologue from Echinococcus multilocularis. 25828812 9 23 contain had 1033:1035 arg2 relationship 1043:1054 close relationship 1037:1054 close relationship with the homologue from Echinococcus multilocularis 1037:1106 Our results showed that the sequence of CsRNASET2 had close relationship with the homologue from Echinococcus multilocularis. 25828812 1 24 theme immune 142:147 arg1 response 149:156 the host immune response 133:156 the host immune response 133:156 Many parasites can trigger the host immune response by releasing excretory/secretory proteins (ESPs). 25828812 2 25 attach present 250:256 arg2 CsRNASET2 208:216 CsRNASET2 208:216 CsRNASET2 208:216 CsRNASET2, a glycosylated T2 ribonuclease present in ESPs of Clonorchis sinensis (C. sinensis, Cs), has recently been reported to possess potent effects in regulating mouse dendritic cells (DCs). 25828812 2 25 attach present 250:256 arg2 ribonuclease 237:248 a glycosylated T2 ribonuclease 219:248 a glycosylated T2 ribonuclease present in ESPs of Clonorchis sinensis (C. sinensis, Cs) 219:305 CsRNASET2, a glycosylated T2 ribonuclease present in ESPs of Clonorchis sinensis (C. sinensis, Cs), has recently been reported to possess potent effects in regulating mouse dendritic cells (DCs). 25828812 2 25 attach present 250:256 arg1 ESPs 261:264 ESPs 261:264 ESPs of Clonorchis sinensis (C. sinensis, Cs) 261:305 CsRNASET2, a glycosylated T2 ribonuclease present in ESPs of Clonorchis sinensis (C. sinensis, Cs), has recently been reported to possess potent effects in regulating mouse dendritic cells (DCs). 25828812 13 26 with consistent 1660:1669 arg1 response 1687:1694 the immune response 1676:1694 the immune response initiated by infection of C. sinensis 1676:1732 Immunization with CsRNASET2 elicited Th2 immune response by promoting the synthesis of IL-4, consistent with the immune response initiated by infection of C. sinensis. 25828812 8 27 theme flow 967:970 arg1 cytometry 972:980 flow cytometry 967:980 flow cytometry 967:980 The expression levels of IL-4 and IFN-γ in splenocytes of immunized mice and infected mice were detected by ELISA and flow cytometry. 25828812 8 28 from levels 864:869 arg1 splenocytes 892:902 splenocytes 892:902 splenocytes of immunized mice and infected mice 892:938 The expression levels of IL-4 and IFN-γ in splenocytes of immunized mice and infected mice were detected by ELISA and flow cytometry. 25828812 10 29 link N-linked 1180:1187 arg1 glycosylation 1189:1201 N-linked glycosylation 1180:1201 N-linked glycosylation region 1180:1208 The conserved active site (CAS) motifs, active histidine residues, and N-linked glycosylation region of CsRNASET2 were close to each other in the three-dimensional structure. 25828812 10 30 theme glycosylation 1189:1201 arg1 region 1203:1208 N-linked glycosylation region 1180:1208 N-linked glycosylation region 1180:1208 The conserved active site (CAS) motifs, active histidine residues, and N-linked glycosylation region of CsRNASET2 were close to each other in the three-dimensional structure. 25828812 0 31 theme immune 89:94 arg1 response 96:103 Th2 immune response 85:103 Th2 immune response 85:103 CsRNASET2 is an important component of Clonorchis sinensis responsible for eliciting Th2 immune response. 25828812 12 32 theme IL-4 1494:1497 arg1 levels 1484:1489 increased levels 1474:1489 increased levels of IL-4 1474:1497 Splenocytes from both CsRNASET2 immunized mice and C. sinensis infected mice expressed increased levels of IL-4, while the production of IFN-γ exhibited no significant difference. 25828812 10 33 from structure 1273:1281 arg1 motifs 1141:1146 The conserved active site (CAS) motifs 1109:1146 The conserved active site (CAS) motifs 1109:1146 The conserved active site (CAS) motifs, active histidine residues, and N-linked glycosylation region of CsRNASET2 were close to each other in the three-dimensional structure. 25828812 10 33 from structure 1273:1281 arg1 other 1242:1246 other 1242:1246 other 1242:1246 The conserved active site (CAS) motifs, active histidine residues, and N-linked glycosylation region of CsRNASET2 were close to each other in the three-dimensional structure. 25828812 13 34 theme IL-4 1654:1657 arg1 synthesis 1641:1649 the synthesis 1637:1649 the synthesis of IL-4 1637:1657 Immunization with CsRNASET2 elicited Th2 immune response by promoting the synthesis of IL-4, consistent with the immune response initiated by infection of C. sinensis. 25828812 11 35 theme titers 1379:1384 arg1 levels 1351:1356 obviously higher levels 1334:1356 obviously higher levels of specific antibody titers 1334:1384 In addition, sera of CsRNASET2 immunized mice had obviously higher levels of specific antibody titers. 25828812 2 36 from present 250:256 arg1 ESPs 261:264 ESPs 261:264 ESPs of Clonorchis sinensis (C. sinensis, Cs) 261:305 CsRNASET2, a glycosylated T2 ribonuclease present in ESPs of Clonorchis sinensis (C. sinensis, Cs), has recently been reported to possess potent effects in regulating mouse dendritic cells (DCs). 25828812 1 37 theme Many 106:109 arg1 parasites 111:119 Many parasites 106:119 Many parasites 106:119 Many parasites can trigger the host immune response by releasing excretory/secretory proteins (ESPs). 25828812 2 38 from ESPs 261:264 arg1 present 250:256 present 250:256 present 250:256 CsRNASET2, a glycosylated T2 ribonuclease present in ESPs of Clonorchis sinensis (C. sinensis, Cs), has recently been reported to possess potent effects in regulating mouse dendritic cells (DCs). 25828812 14 39 theme C. 1805:1806 arg1 sinensis 1808:1815 C. sinensis 1805:1815 C. sinensis 1805:1815 Taken together, these data suggested that CsRNASET2 was important for C. sinensis to trigger Th2 immune response. 25828812 2 40 theme dendritic 381:389 arg1 DCs 398:400 DCs 398:400 DCs 398:400 CsRNASET2, a glycosylated T2 ribonuclease present in ESPs of Clonorchis sinensis (C. sinensis, Cs), has recently been reported to possess potent effects in regulating mouse dendritic cells (DCs). 25828812 2 40 theme dendritic 381:389 arg1 cells 391:395 mouse dendritic cells 375:395 mouse dendritic cells (DCs) 375:401 CsRNASET2, a glycosylated T2 ribonuclease present in ESPs of Clonorchis sinensis (C. sinensis, Cs), has recently been reported to possess potent effects in regulating mouse dendritic cells (DCs). 25828812 10 41 theme active 1123:1128 arg1 CAS 1136:1138 CAS 1136:1138 CAS 1136:1138 The conserved active site (CAS) motifs, active histidine residues, and N-linked glycosylation region of CsRNASET2 were close to each other in the three-dimensional structure. 25828812 10 41 theme active 1123:1128 arg1 site 1130:1133 active site 1123:1133 The conserved active site (CAS) motifs 1109:1146 The conserved active site (CAS) motifs, active histidine residues, and N-linked glycosylation region of CsRNASET2 were close to each other in the three-dimensional structure. 25828812 12 42 theme increased 1474:1482 arg1 levels 1484:1489 increased levels 1474:1489 increased levels of IL-4 1474:1497 Splenocytes from both CsRNASET2 immunized mice and C. sinensis infected mice expressed increased levels of IL-4, while the production of IFN-γ exhibited no significant difference. 25828812 0 43 theme Clonorchis 39:48 arg1 sinensis 50:57 Clonorchis sinensis 39:57 Clonorchis sinensis 39:57 CsRNASET2 is an important component of Clonorchis sinensis responsible for eliciting Th2 immune response. 25828812 13 44 theme Th2 1604:1606 arg1 response 1615:1622 Th2 immune response 1604:1622 Th2 immune response 1604:1622 Immunization with CsRNASET2 elicited Th2 immune response by promoting the synthesis of IL-4, consistent with the immune response initiated by infection of C. sinensis. 25828812 9 45 theme close 1037:1041 arg1 relationship 1043:1054 close relationship 1037:1054 close relationship with the homologue from Echinococcus multilocularis 1037:1106 Our results showed that the sequence of CsRNASET2 had close relationship with the homologue from Echinococcus multilocularis. 25828812 12 46 theme sinensis 1441:1448 arg1 mice 1459:1462 C. sinensis infected mice 1438:1462 C. sinensis infected mice 1438:1462 Splenocytes from both CsRNASET2 immunized mice and C. sinensis infected mice expressed increased levels of IL-4, while the production of IFN-γ exhibited no significant difference. 25828812 8 47 theme mice 917:920 arg1 splenocytes 892:902 splenocytes 892:902 splenocytes of immunized mice and infected mice 892:938 The expression levels of IL-4 and IFN-γ in splenocytes of immunized mice and infected mice were detected by ELISA and flow cytometry. 25828812 11 48 theme immunized 1315:1323 arg1 mice 1325:1328 CsRNASET2 immunized mice 1305:1328 CsRNASET2 immunized mice 1305:1328 In addition, sera of CsRNASET2 immunized mice had obviously higher levels of specific antibody titers. 25828812 3 49 theme adaptive 456:463 arg1 response 472:479 adaptive immune response 456:479 adaptive immune response 456:479 However, it is unclear whether CsRNASET2 can induce adaptive immune response. 25828812 10 50 theme histidine 1156:1164 arg1 residues 1166:1173 active histidine residues 1149:1173 active histidine residues 1149:1173 The conserved active site (CAS) motifs, active histidine residues, and N-linked glycosylation region of CsRNASET2 were close to each other in the three-dimensional structure. 25828812 10 50 theme histidine 1156:1164 arg1 CsRNASET2 1213:1221 CsRNASET2 1213:1221 CsRNASET2 1213:1221 The conserved active site (CAS) motifs, active histidine residues, and N-linked glycosylation region of CsRNASET2 were close to each other in the three-dimensional structure. 25828812 12 51 theme immunized 1419:1427 arg1 mice 1429:1432 CsRNASET2 immunized mice 1409:1432 CsRNASET2 immunized mice 1409:1432 Splenocytes from both CsRNASET2 immunized mice and C. sinensis infected mice expressed increased levels of IL-4, while the production of IFN-γ exhibited no significant difference. 25828812 8 52 theme infected 926:933 arg1 mice 935:938 infected mice 926:938 infected mice 926:938 The expression levels of IL-4 and IFN-γ in splenocytes of immunized mice and infected mice were detected by ELISA and flow cytometry. 25828812 4 53 theme biochemical 538:548 arg1 features 550:557 biochemical features 538:557 biochemical features of CsRNASET2 538:570 In this study, we carried out further investigations on biochemical features of CsRNASET2. 25828812 11 54 theme higher 1344:1349 arg1 levels 1351:1356 obviously higher levels 1334:1356 obviously higher levels of specific antibody titers 1334:1384 In addition, sera of CsRNASET2 immunized mice had obviously higher levels of specific antibody titers. 25828812 6 55 theme antibody 751:758 arg1 titers 760:765 specific antibody titers 742:765 specific antibody titers 742:765 Sera of immunized mice were collected and evaluated for specific antibody titers by ELISA. 25828812 2 56 theme Clonorchis 269:278 arg1 sinensis 280:287 Clonorchis sinensis 269:287 Clonorchis sinensis (C. sinensis, Cs) 269:305 CsRNASET2, a glycosylated T2 ribonuclease present in ESPs of Clonorchis sinensis (C. sinensis, Cs), has recently been reported to possess potent effects in regulating mouse dendritic cells (DCs). 25828812 2 56 theme Clonorchis 269:278 arg1 sinensis 293:300 C. sinensis 290:300 C. sinensis 290:300 CsRNASET2, a glycosylated T2 ribonuclease present in ESPs of Clonorchis sinensis (C. sinensis, Cs), has recently been reported to possess potent effects in regulating mouse dendritic cells (DCs). 25828812 13 57 theme sinensis 1725:1732 arg1 infection 1709:1717 infection 1709:1717 infection of C. sinensis 1709:1732 Immunization with CsRNASET2 elicited Th2 immune response by promoting the synthesis of IL-4, consistent with the immune response initiated by infection of C. sinensis. 25828812 7 58 theme experimental 792:803 arg1 mice 805:808 experimental mice 792:808 experimental mice 792:808 Splenocytes of experimental mice were isolated and stimulated in vitro. 25828812 11 59 contain had 1330:1332 arg1 sera 1297:1300 sera 1297:1300 sera of CsRNASET2 immunized mice 1297:1328 In addition, sera of CsRNASET2 immunized mice had obviously higher levels of specific antibody titers. 25828812 11 59 contain had 1330:1332 arg2 levels 1351:1356 obviously higher levels 1334:1356 obviously higher levels of specific antibody titers 1334:1384 In addition, sera of CsRNASET2 immunized mice had obviously higher levels of specific antibody titers. 25828812 9 60 from multilocularis 1093:1106 arg1 homologue 1065:1073 the homologue 1061:1073 the homologue from Echinococcus multilocularis 1061:1106 Our results showed that the sequence of CsRNASET2 had close relationship with the homologue from Echinococcus multilocularis. 25828812 2 61 gly glycosylated 221:232 arg1 ribonuclease 237:248 a glycosylated T2 ribonuclease 219:248 a glycosylated T2 ribonuclease present in ESPs of Clonorchis sinensis (C. sinensis, Cs) 219:305 CsRNASET2, a glycosylated T2 ribonuclease present in ESPs of Clonorchis sinensis (C. sinensis, Cs), has recently been reported to possess potent effects in regulating mouse dendritic cells (DCs). 25828812 2 61 gly glycosylated 221:232 arg1 CsRNASET2 208:216 CsRNASET2 208:216 CsRNASET2 208:216 CsRNASET2, a glycosylated T2 ribonuclease present in ESPs of Clonorchis sinensis (C. sinensis, Cs), has recently been reported to possess potent effects in regulating mouse dendritic cells (DCs). 25828812 2 62 theme T2 234:235 arg1 ribonuclease 237:248 a glycosylated T2 ribonuclease 219:248 a glycosylated T2 ribonuclease present in ESPs of Clonorchis sinensis (C. sinensis, Cs) 219:305 CsRNASET2, a glycosylated T2 ribonuclease present in ESPs of Clonorchis sinensis (C. sinensis, Cs), has recently been reported to possess potent effects in regulating mouse dendritic cells (DCs). 25828812 2 62 theme T2 234:235 arg1 CsRNASET2 208:216 CsRNASET2 208:216 CsRNASET2 208:216 CsRNASET2, a glycosylated T2 ribonuclease present in ESPs of Clonorchis sinensis (C. sinensis, Cs), has recently been reported to possess potent effects in regulating mouse dendritic cells (DCs). 25828812 9 63 with relationship 1043:1054 arg1 homologue 1065:1073 the homologue 1061:1073 the homologue from Echinococcus multilocularis 1061:1106 Our results showed that the sequence of CsRNASET2 had close relationship with the homologue from Echinococcus multilocularis. 25828812 14 64 theme Th2 1828:1830 arg1 response 1839:1846 Th2 immune response 1828:1846 Th2 immune response 1828:1846 Taken together, these data suggested that CsRNASET2 was important for C. sinensis to trigger Th2 immune response. 25828812 12 65 from mice 1429:1432 arg1 Splenocytes 1387:1397 Splenocytes 1387:1397 Splenocytes from both CsRNASET2 immunized mice and C. sinensis infected mice 1387:1462 Splenocytes from both CsRNASET2 immunized mice and C. sinensis infected mice expressed increased levels of IL-4, while the production of IFN-γ exhibited no significant difference. 25828812 12 66 theme significant 1543:1553 arg1 difference 1555:1564 no significant difference 1540:1564 no significant difference 1540:1564 Splenocytes from both CsRNASET2 immunized mice and C. sinensis infected mice expressed increased levels of IL-4, while the production of IFN-γ exhibited no significant difference. 25828812 10 67 theme N-linked 1180:1187 arg1 glycosylation 1189:1201 N-linked glycosylation 1180:1201 N-linked glycosylation region 1180:1208 The conserved active site (CAS) motifs, active histidine residues, and N-linked glycosylation region of CsRNASET2 were close to each other in the three-dimensional structure. 25828812 5 68 theme Balb/c 642:647 arg1 mice 649:652 Balb/c mice 642:652 Balb/c mice 642:652 Besides, we immunized Balb/c mice with CsRNASET2 and orally infected Balb/c mice with C. sinensis, respectively. 25828812 6 69 theme immunized 694:702 arg1 mice 704:707 immunized mice 694:707 immunized mice 694:707 Sera of immunized mice were collected and evaluated for specific antibody titers by ELISA. 25828812 10 70 from other 1242:1246 arg1 structure 1273:1281 the three-dimensional structure 1251:1281 the three-dimensional structure 1251:1281 The conserved active site (CAS) motifs, active histidine residues, and N-linked glycosylation region of CsRNASET2 were close to each other in the three-dimensional structure. 25828812 2 71 theme present 250:256 arg1 ribonuclease 237:248 a glycosylated T2 ribonuclease 219:248 a glycosylated T2 ribonuclease present in ESPs of Clonorchis sinensis (C. sinensis, Cs) 219:305 CsRNASET2, a glycosylated T2 ribonuclease present in ESPs of Clonorchis sinensis (C. sinensis, Cs), has recently been reported to possess potent effects in regulating mouse dendritic cells (DCs). 25828812 2 71 theme present 250:256 arg1 CsRNASET2 208:216 CsRNASET2 208:216 CsRNASET2 208:216 CsRNASET2, a glycosylated T2 ribonuclease present in ESPs of Clonorchis sinensis (C. sinensis, Cs), has recently been reported to possess potent effects in regulating mouse dendritic cells (DCs). 25828812 1 72 theme host 137:140 arg1 response 149:156 the host immune response 133:156 the host immune response 133:156 Many parasites can trigger the host immune response by releasing excretory/secretory proteins (ESPs). 25828812 10 73 theme CsRNASET2 1213:1221 arg1 region 1203:1208 N-linked glycosylation region 1180:1208 N-linked glycosylation region 1180:1208 The conserved active site (CAS) motifs, active histidine residues, and N-linked glycosylation region of CsRNASET2 were close to each other in the three-dimensional structure. 25828812 10 73 theme CsRNASET2 1213:1221 arg1 residues 1166:1173 active histidine residues 1149:1173 active histidine residues 1149:1173 The conserved active site (CAS) motifs, active histidine residues, and N-linked glycosylation region of CsRNASET2 were close to each other in the three-dimensional structure. 25828812 10 73 theme CsRNASET2 1213:1221 arg1 other 1242:1246 other 1242:1246 other 1242:1246 The conserved active site (CAS) motifs, active histidine residues, and N-linked glycosylation region of CsRNASET2 were close to each other in the three-dimensional structure. 25828812 10 73 theme CsRNASET2 1213:1221 arg1 motifs 1141:1146 The conserved active site (CAS) motifs 1109:1146 The conserved active site (CAS) motifs 1109:1146 The conserved active site (CAS) motifs, active histidine residues, and N-linked glycosylation region of CsRNASET2 were close to each other in the three-dimensional structure. 25828812 10 73 theme CsRNASET2 1213:1221 arg1 CsRNASET2 1213:1221 CsRNASET2 1213:1221 CsRNASET2 1213:1221 The conserved active site (CAS) motifs, active histidine residues, and N-linked glycosylation region of CsRNASET2 were close to each other in the three-dimensional structure. 25828812 0 74 theme Th2 85:87 arg1 response 96:103 Th2 immune response 85:103 Th2 immune response 85:103 CsRNASET2 is an important component of Clonorchis sinensis responsible for eliciting Th2 immune response. 25828812 13 75 theme immune 1680:1685 arg1 response 1687:1694 the immune response 1676:1694 the immune response initiated by infection of C. sinensis 1676:1732 Immunization with CsRNASET2 elicited Th2 immune response by promoting the synthesis of IL-4, consistent with the immune response initiated by infection of C. sinensis. 25828812 11 76 theme antibody 1370:1377 arg1 titers 1379:1384 specific antibody titers 1361:1384 specific antibody titers 1361:1384 In addition, sera of CsRNASET2 immunized mice had obviously higher levels of specific antibody titers. 25828812 2 77 contain possess 338:344 arg1 ribonuclease 237:248 a glycosylated T2 ribonuclease 219:248 a glycosylated T2 ribonuclease present in ESPs of Clonorchis sinensis (C. sinensis, Cs) 219:305 CsRNASET2, a glycosylated T2 ribonuclease present in ESPs of Clonorchis sinensis (C. sinensis, Cs), has recently been reported to possess potent effects in regulating mouse dendritic cells (DCs). 25828812 2 77 contain possess 338:344 arg2 effects 353:359 potent effects 346:359 potent effects 346:359 CsRNASET2, a glycosylated T2 ribonuclease present in ESPs of Clonorchis sinensis (C. sinensis, Cs), has recently been reported to possess potent effects in regulating mouse dendritic cells (DCs). 25828812 2 77 contain possess 338:344 arg1 CsRNASET2 208:216 CsRNASET2 208:216 CsRNASET2 208:216 CsRNASET2, a glycosylated T2 ribonuclease present in ESPs of Clonorchis sinensis (C. sinensis, Cs), has recently been reported to possess potent effects in regulating mouse dendritic cells (DCs). 25828812 10 78 theme three-dimensional 1255:1271 arg1 structure 1273:1281 the three-dimensional structure 1251:1281 the three-dimensional structure 1251:1281 The conserved active site (CAS) motifs, active histidine residues, and N-linked glycosylation region of CsRNASET2 were close to each other in the three-dimensional structure. 25828812 2 79 theme potent 346:351 arg1 effects 353:359 potent effects 346:359 potent effects 346:359 CsRNASET2, a glycosylated T2 ribonuclease present in ESPs of Clonorchis sinensis (C. sinensis, Cs), has recently been reported to possess potent effects in regulating mouse dendritic cells (DCs). 25828812 0 80 theme important 16:24 arg1 CsRNASET2 0:8 CsRNASET2 0:8 CsRNASET2 0:8 CsRNASET2 is an important component of Clonorchis sinensis responsible for eliciting Th2 immune response. 25828812 0 80 theme important 16:24 arg1 component 26:34 an important component 13:34 an important component of Clonorchis sinensis responsible for eliciting Th2 immune response 13:103 CsRNASET2 is an important component of Clonorchis sinensis responsible for eliciting Th2 immune response. 25828812 4 81 theme further 512:518 arg1 investigations 520:533 further investigations 512:533 further investigations 512:533 In this study, we carried out further investigations on biochemical features of CsRNASET2. 25828812 13 82 with Immunization 1567:1578 arg1 CsRNASET2 1585:1593 CsRNASET2 1585:1593 CsRNASET2 1585:1593 Immunization with CsRNASET2 elicited Th2 immune response by promoting the synthesis of IL-4, consistent with the immune response initiated by infection of C. sinensis. 25828812 12 83 theme infected 1450:1457 arg1 mice 1459:1462 C. sinensis infected mice 1438:1462 C. sinensis infected mice 1438:1462 Splenocytes from both CsRNASET2 immunized mice and C. sinensis infected mice expressed increased levels of IL-4, while the production of IFN-γ exhibited no significant difference. 25828812 2 84 theme mouse 375:379 arg1 DCs 398:400 DCs 398:400 DCs 398:400 CsRNASET2, a glycosylated T2 ribonuclease present in ESPs of Clonorchis sinensis (C. sinensis, Cs), has recently been reported to possess potent effects in regulating mouse dendritic cells (DCs). 25828812 2 84 theme mouse 375:379 arg1 cells 391:395 mouse dendritic cells 375:395 mouse dendritic cells (DCs) 375:401 CsRNASET2, a glycosylated T2 ribonuclease present in ESPs of Clonorchis sinensis (C. sinensis, Cs), has recently been reported to possess potent effects in regulating mouse dendritic cells (DCs). 25828812 0 85 theme sinensis 50:57 arg1 CsRNASET2 0:8 CsRNASET2 0:8 CsRNASET2 0:8 CsRNASET2 is an important component of Clonorchis sinensis responsible for eliciting Th2 immune response. 25828812 0 85 theme sinensis 50:57 arg1 component 26:34 an important component 13:34 an important component of Clonorchis sinensis responsible for eliciting Th2 immune response 13:103 CsRNASET2 is an important component of Clonorchis sinensis responsible for eliciting Th2 immune response. 25828812 10 86 theme conserved 1113:1121 arg1 other 1242:1246 other 1242:1246 other 1242:1246 The conserved active site (CAS) motifs, active histidine residues, and N-linked glycosylation region of CsRNASET2 were close to each other in the three-dimensional structure. 25828812 10 86 theme conserved 1113:1121 arg1 motifs 1141:1146 The conserved active site (CAS) motifs 1109:1146 The conserved active site (CAS) motifs 1109:1146 The conserved active site (CAS) motifs, active histidine residues, and N-linked glycosylation region of CsRNASET2 were close to each other in the three-dimensional structure. 25828812 8 87 theme IL-4 874:877 arg1 levels 864:869 The expression levels 849:869 The expression levels of IL-4 and IFN-γ in splenocytes of immunized mice and infected mice 849:938 The expression levels of IL-4 and IFN-γ in splenocytes of immunized mice and infected mice were detected by ELISA and flow cytometry. 25828812 6 88 theme mice 704:707 arg1 Sera 686:689 Sera 686:689 Sera of immunized mice 686:707 Sera of immunized mice were collected and evaluated for specific antibody titers by ELISA. 25828812 8 89 theme IFN-γ 883:887 arg1 levels 864:869 The expression levels 849:869 The expression levels of IL-4 and IFN-γ in splenocytes of immunized mice and infected mice 849:938 The expression levels of IL-4 and IFN-γ in splenocytes of immunized mice and infected mice were detected by ELISA and flow cytometry. 25828812 4 90 theme CsRNASET2 562:570 arg1 features 550:557 biochemical features 538:557 biochemical features of CsRNASET2 538:570 In this study, we carried out further investigations on biochemical features of CsRNASET2. 25828812 13 91 theme immune 1608:1613 arg1 response 1615:1622 Th2 immune response 1604:1622 Th2 immune response 1604:1622 Immunization with CsRNASET2 elicited Th2 immune response by promoting the synthesis of IL-4, consistent with the immune response initiated by infection of C. sinensis. 25828812 9 92 theme CsRNASET2 1023:1031 arg1 sequence 1011:1018 the sequence 1007:1018 the sequence of CsRNASET2 1007:1031 Our results showed that the sequence of CsRNASET2 had close relationship with the homologue from Echinococcus multilocularis. 25828812 12 93 theme C. 1438:1439 arg1 mice 1459:1462 C. sinensis infected mice 1438:1462 C. sinensis infected mice 1438:1462 Splenocytes from both CsRNASET2 immunized mice and C. sinensis infected mice expressed increased levels of IL-4, while the production of IFN-γ exhibited no significant difference. 25828812 10 94 theme site 1130:1133 arg1 other 1242:1246 other 1242:1246 other 1242:1246 The conserved active site (CAS) motifs, active histidine residues, and N-linked glycosylation region of CsRNASET2 were close to each other in the three-dimensional structure. 25828812 10 94 theme site 1130:1133 arg1 motifs 1141:1146 The conserved active site (CAS) motifs 1109:1146 The conserved active site (CAS) motifs 1109:1146 The conserved active site (CAS) motifs, active histidine residues, and N-linked glycosylation region of CsRNASET2 were close to each other in the three-dimensional structure. 24342833 6 0 theme transcriptional 1124:1138 arg1 site 986:989 a site 984:989 a site for O-GlcNAc modification which regulated its subcellular distribution 984:1060 RESULTS: Serine 23 of β-catenin was determined as a site for O-GlcNAc modification which regulated its subcellular distribution, its interactions with cellular partners and consequently its transcriptional activity. 24342833 6 0 theme transcriptional 1124:1138 arg1 activity 1140:1147 consequently its transcriptional activity 1107:1147 consequently its transcriptional activity 1107:1147 RESULTS: Serine 23 of β-catenin was determined as a site for O-GlcNAc modification which regulated its subcellular distribution, its interactions with cellular partners and consequently its transcriptional activity. 24342833 7 1 theme transcriptional 1273:1287 arg1 activity 1289:1296 transcriptional activity 1273:1296 transcriptional activity 1273:1296 SIGNIFICANCE: O-GlcNAcylation of Serine 23 is a novel regulatory modification for β-catenin's subcellular localization and transcriptional activity. 24342833 8 2 theme first 1317:1321 arg1 study 1304:1308 This study 1299:1308 This study 1299:1308 This study is the first report to characterize site specific regulation of β-catenin by the O-GlcNAc modification. 24342833 8 2 theme first 1317:1321 arg1 report 1323:1328 the first report 1313:1328 the first report to characterize site specific regulation of β-catenin by the O-GlcNAc modification 1313:1411 This study is the first report to characterize site specific regulation of β-catenin by the O-GlcNAc modification. 24342833 1 3 mod modified 211:218 arg3 attachment 243:252 a single O-linked attachment 225:252 a single O-linked attachment of β-N-acetyl-glucosamine (O-GlcNAc) 225:289 BACKGROUND: We have previously reported that β-catenin is post-translationally modified with a single O-linked attachment of β-N-acetyl-glucosamine (O-GlcNAc). 24342833 1 3 mod modified 211:218 arg1 β-catenin 177:185 β-catenin 177:185 β-catenin 177:185 BACKGROUND: We have previously reported that β-catenin is post-translationally modified with a single O-linked attachment of β-N-acetyl-glucosamine (O-GlcNAc). 24342833 4 4 theme Missense 621:628 arg1 mutations 630:638 Missense mutations 621:638 Missense mutations 621:638 METHOD: Missense mutations were introduced to potential O-GlcNAc sites of pEGFP-C2-N-Terminal- or pEGFP-C2-Wild Type-β-catenin by site-directed mutagenesis. 24342833 5 5 theme subcellular 818:828 arg1 localization 830:841 subcellular localization 818:841 subcellular localization 818:841 We determined the levels of O-GlcNAc-β-catenin, subcellular localization, interaction with binding partners and transcriptional activity of the various constructs. 24342833 7 6 theme subcellular 1244:1254 arg1 localization 1256:1267 β-catenin's subcellular localization 1232:1267 β-catenin's subcellular localization 1232:1267 SIGNIFICANCE: O-GlcNAcylation of Serine 23 is a novel regulatory modification for β-catenin's subcellular localization and transcriptional activity. 24342833 0 7 theme subcellular 78:88 arg1 localization 90:101 β-catenin's subcellular localization 66:101 β-catenin's subcellular localization 66:101 β-catenin is O-GlcNAc glycosylated at Serine 23: implications for β-catenin's subcellular localization and transactivator function. 24342833 6 8 theme O-GlcNAc 995:1002 arg1 modification 1004:1015 O-GlcNAc modification 995:1015 O-GlcNAc modification 995:1015 RESULTS: Serine 23 of β-catenin was determined as a site for O-GlcNAc modification which regulated its subcellular distribution, its interactions with cellular partners and consequently its transcriptional activity. 24342833 6 9 with interactions 1067:1078 arg1 partners 1094:1101 cellular partners 1085:1101 cellular partners 1085:1101 RESULTS: Serine 23 of β-catenin was determined as a site for O-GlcNAc modification which regulated its subcellular distribution, its interactions with cellular partners and consequently its transcriptional activity. 24342833 3 10 theme transcriptional 587:601 arg1 activity 603:610 transcriptional activity 587:610 transcriptional activity 587:610 OBJECTIVE: The objectives of this investigation were to identify the putative O-GlcNAc sites of β-catenin and the relevance of identified sites in the regulation of β-catenin's localization and transcriptional activity. 24342833 0 11 theme transactivator 107:120 arg1 function 122:129 transactivator function 107:129 transactivator function 107:129 β-catenin is O-GlcNAc glycosylated at Serine 23: implications for β-catenin's subcellular localization and transactivator function. 24342833 8 12 theme O-GlcNAc 1391:1398 arg1 modification 1400:1411 the O-GlcNAc modification 1387:1411 the O-GlcNAc modification 1387:1411 This study is the first report to characterize site specific regulation of β-catenin by the O-GlcNAc modification. 24342833 5 13 theme interaction 844:854 arg1 levels 788:793 the levels 784:793 the levels of O-GlcNAc-β-catenin, subcellular localization, interaction with binding partners and transcriptional activity of the various constructs 784:931 We determined the levels of O-GlcNAc-β-catenin, subcellular localization, interaction with binding partners and transcriptional activity of the various constructs. 24342833 6 14 theme cellular 1085:1092 arg1 partners 1094:1101 cellular partners 1085:1101 cellular partners 1085:1101 RESULTS: Serine 23 of β-catenin was determined as a site for O-GlcNAc modification which regulated its subcellular distribution, its interactions with cellular partners and consequently its transcriptional activity. 24342833 3 15 theme localization 570:581 arg1 regulation 544:553 the regulation 540:553 the regulation of β-catenin's localization and transcriptional activity 540:610 OBJECTIVE: The objectives of this investigation were to identify the putative O-GlcNAc sites of β-catenin and the relevance of identified sites in the regulation of β-catenin's localization and transcriptional activity. 24342833 7 16 dep SIGNIFICANCE 1150:1161 arg1 O-GlcNAcylation 1164:1178 O-GlcNAcylation 1164:1178 SIGNIFICANCE: O-GlcNAcylation of Serine 23 1150:1191 SIGNIFICANCE: O-GlcNAcylation of Serine 23 is a novel regulatory modification for β-catenin's subcellular localization and transcriptional activity. 24342833 4 17 theme Type-β-catenin 725:738 arg1 Type-β-catenin 725:738 pEGFP-C2-N-Terminal- or pEGFP-C2-Wild Type-β-catenin 687:738 pEGFP-C2-N-Terminal- or pEGFP-C2-Wild Type-β-catenin 687:738 METHOD: Missense mutations were introduced to potential O-GlcNAc sites of pEGFP-C2-N-Terminal- or pEGFP-C2-Wild Type-β-catenin by site-directed mutagenesis. 24342833 4 17 theme Type-β-catenin 725:738 arg1 sites 678:682 potential O-GlcNAc sites 659:682 potential O-GlcNAc sites of pEGFP-C2-N-Terminal- or pEGFP-C2-Wild Type-β-catenin 659:738 METHOD: Missense mutations were introduced to potential O-GlcNAc sites of pEGFP-C2-N-Terminal- or pEGFP-C2-Wild Type-β-catenin by site-directed mutagenesis. 24342833 5 18 theme various 914:920 arg1 constructs 922:931 the various constructs 910:931 the various constructs 910:931 We determined the levels of O-GlcNAc-β-catenin, subcellular localization, interaction with binding partners and transcriptional activity of the various constructs. 24342833 2 19 theme subcellular 338:348 arg1 localization 350:361 β-catenin's subcellular localization 326:361 β-catenin's subcellular localization 326:361 We showed that O-GlcNAc regulated β-catenin's subcellular localization and transcriptional activity. 24342833 3 20 theme putative 462:469 arg1 sites 480:484 the putative O-GlcNAc sites 458:484 the putative O-GlcNAc sites of β-catenin 458:497 OBJECTIVE: The objectives of this investigation were to identify the putative O-GlcNAc sites of β-catenin and the relevance of identified sites in the regulation of β-catenin's localization and transcriptional activity. 24342833 3 20 theme putative 462:469 arg1 sites 531:535 identified sites 520:535 identified sites 520:535 OBJECTIVE: The objectives of this investigation were to identify the putative O-GlcNAc sites of β-catenin and the relevance of identified sites in the regulation of β-catenin's localization and transcriptional activity. 24342833 3 20 theme putative 462:469 arg1 β-catenin 489:497 β-catenin 489:497 β-catenin 489:497 OBJECTIVE: The objectives of this investigation were to identify the putative O-GlcNAc sites of β-catenin and the relevance of identified sites in the regulation of β-catenin's localization and transcriptional activity. 24342833 3 21 theme investigation 427:439 arg1 objectives 408:417 The objectives 404:417 The objectives of this investigation 404:439 OBJECTIVE: The objectives of this investigation were to identify the putative O-GlcNAc sites of β-catenin and the relevance of identified sites in the regulation of β-catenin's localization and transcriptional activity. 24342833 1 22 link O-linked 234:241 arg1 attachment 243:252 a single O-linked attachment 225:252 a single O-linked attachment of β-N-acetyl-glucosamine (O-GlcNAc) 225:289 BACKGROUND: We have previously reported that β-catenin is post-translationally modified with a single O-linked attachment of β-N-acetyl-glucosamine (O-GlcNAc). 24342833 3 23 theme O-GlcNAc 471:478 arg1 sites 480:484 the putative O-GlcNAc sites 458:484 the putative O-GlcNAc sites of β-catenin 458:497 OBJECTIVE: The objectives of this investigation were to identify the putative O-GlcNAc sites of β-catenin and the relevance of identified sites in the regulation of β-catenin's localization and transcriptional activity. 24342833 3 23 theme O-GlcNAc 471:478 arg1 sites 531:535 identified sites 520:535 identified sites 520:535 OBJECTIVE: The objectives of this investigation were to identify the putative O-GlcNAc sites of β-catenin and the relevance of identified sites in the regulation of β-catenin's localization and transcriptional activity. 24342833 3 23 theme O-GlcNAc 471:478 arg1 β-catenin 489:497 β-catenin 489:497 β-catenin 489:497 OBJECTIVE: The objectives of this investigation were to identify the putative O-GlcNAc sites of β-catenin and the relevance of identified sites in the regulation of β-catenin's localization and transcriptional activity. 24342833 8 24 theme specific 1351:1358 arg1 regulation 1360:1369 site specific regulation 1346:1369 site specific regulation of β-catenin by the O-GlcNAc modification 1346:1411 This study is the first report to characterize site specific regulation of β-catenin by the O-GlcNAc modification. 24342833 5 25 theme constructs 922:931 arg1 interaction 844:854 interaction 844:854 interaction with binding partners 844:876 We determined the levels of O-GlcNAc-β-catenin, subcellular localization, interaction with binding partners and transcriptional activity of the various constructs. 24342833 5 25 theme constructs 922:931 arg1 O-GlcNAc-β-catenin 798:815 O-GlcNAc-β-catenin 798:815 O-GlcNAc-β-catenin 798:815 We determined the levels of O-GlcNAc-β-catenin, subcellular localization, interaction with binding partners and transcriptional activity of the various constructs. 24342833 5 25 theme constructs 922:931 arg1 localization 830:841 subcellular localization 818:841 subcellular localization 818:841 We determined the levels of O-GlcNAc-β-catenin, subcellular localization, interaction with binding partners and transcriptional activity of the various constructs. 24342833 5 25 theme constructs 922:931 arg1 activity 898:905 transcriptional activity 882:905 transcriptional activity of the various constructs 882:931 We determined the levels of O-GlcNAc-β-catenin, subcellular localization, interaction with binding partners and transcriptional activity of the various constructs. 24342833 7 26 theme novel 1198:1202 arg1 modification 1215:1226 a novel regulatory modification 1196:1226 a novel regulatory modification for β-catenin's subcellular localization and transcriptional activity 1196:1296 SIGNIFICANCE: O-GlcNAcylation of Serine 23 is a novel regulatory modification for β-catenin's subcellular localization and transcriptional activity. 24342833 7 26 theme novel 1198:1202 arg1 SIGNIFICANCE 1150:1161 SIGNIFICANCE 1150:1161 SIGNIFICANCE: O-GlcNAcylation of Serine 23 1150:1191 SIGNIFICANCE: O-GlcNAcylation of Serine 23 is a novel regulatory modification for β-catenin's subcellular localization and transcriptional activity. 24342833 5 27 with localization 830:841 arg1 partners 869:876 binding partners 861:876 binding partners 861:876 We determined the levels of O-GlcNAc-β-catenin, subcellular localization, interaction with binding partners and transcriptional activity of the various constructs. 24342833 3 28 theme activity 603:610 arg1 regulation 544:553 the regulation 540:553 the regulation of β-catenin's localization and transcriptional activity 540:610 OBJECTIVE: The objectives of this investigation were to identify the putative O-GlcNAc sites of β-catenin and the relevance of identified sites in the regulation of β-catenin's localization and transcriptional activity. 24342833 4 29 theme pEGFP-C2-N-Terminal- 687:706 arg1 Type-β-catenin 725:738 pEGFP-C2-N-Terminal- or pEGFP-C2-Wild Type-β-catenin 687:738 pEGFP-C2-N-Terminal- or pEGFP-C2-Wild Type-β-catenin 687:738 METHOD: Missense mutations were introduced to potential O-GlcNAc sites of pEGFP-C2-N-Terminal- or pEGFP-C2-Wild Type-β-catenin by site-directed mutagenesis. 24342833 7 30 theme regulatory 1204:1213 arg1 modification 1215:1226 a novel regulatory modification 1196:1226 a novel regulatory modification for β-catenin's subcellular localization and transcriptional activity 1196:1296 SIGNIFICANCE: O-GlcNAcylation of Serine 23 is a novel regulatory modification for β-catenin's subcellular localization and transcriptional activity. 24342833 7 30 theme regulatory 1204:1213 arg1 SIGNIFICANCE 1150:1161 SIGNIFICANCE 1150:1161 SIGNIFICANCE: O-GlcNAcylation of Serine 23 1150:1191 SIGNIFICANCE: O-GlcNAcylation of Serine 23 is a novel regulatory modification for β-catenin's subcellular localization and transcriptional activity. 24342833 5 31 theme transcriptional 882:896 arg1 activity 898:905 transcriptional activity 882:905 transcriptional activity of the various constructs 882:931 We determined the levels of O-GlcNAc-β-catenin, subcellular localization, interaction with binding partners and transcriptional activity of the various constructs. 24342833 5 32 theme O-GlcNAc-β-catenin 798:815 arg1 levels 788:793 the levels 784:793 the levels of O-GlcNAc-β-catenin, subcellular localization, interaction with binding partners and transcriptional activity of the various constructs 784:931 We determined the levels of O-GlcNAc-β-catenin, subcellular localization, interaction with binding partners and transcriptional activity of the various constructs. 24342833 4 33 theme pEGFP-C2-Wild 711:723 arg1 Type-β-catenin 725:738 pEGFP-C2-N-Terminal- or pEGFP-C2-Wild Type-β-catenin 687:738 pEGFP-C2-N-Terminal- or pEGFP-C2-Wild Type-β-catenin 687:738 METHOD: Missense mutations were introduced to potential O-GlcNAc sites of pEGFP-C2-N-Terminal- or pEGFP-C2-Wild Type-β-catenin by site-directed mutagenesis. 24342833 4 34 theme site-directed 743:755 arg1 mutagenesis 757:767 site-directed mutagenesis 743:767 site-directed mutagenesis 743:767 METHOD: Missense mutations were introduced to potential O-GlcNAc sites of pEGFP-C2-N-Terminal- or pEGFP-C2-Wild Type-β-catenin by site-directed mutagenesis. 24342833 3 35 theme β-catenin 489:497 arg1 sites 480:484 the putative O-GlcNAc sites 458:484 the putative O-GlcNAc sites of β-catenin 458:497 OBJECTIVE: The objectives of this investigation were to identify the putative O-GlcNAc sites of β-catenin and the relevance of identified sites in the regulation of β-catenin's localization and transcriptional activity. 24342833 3 35 theme β-catenin 489:497 arg1 sites 531:535 identified sites 520:535 identified sites 520:535 OBJECTIVE: The objectives of this investigation were to identify the putative O-GlcNAc sites of β-catenin and the relevance of identified sites in the regulation of β-catenin's localization and transcriptional activity. 24342833 3 35 theme β-catenin 489:497 arg1 β-catenin 489:497 β-catenin 489:497 β-catenin 489:497 OBJECTIVE: The objectives of this investigation were to identify the putative O-GlcNAc sites of β-catenin and the relevance of identified sites in the regulation of β-catenin's localization and transcriptional activity. 24342833 3 35 theme β-catenin 489:497 arg1 relevance 507:515 the relevance 503:515 the relevance of identified sites 503:535 OBJECTIVE: The objectives of this investigation were to identify the putative O-GlcNAc sites of β-catenin and the relevance of identified sites in the regulation of β-catenin's localization and transcriptional activity. 24342833 5 36 theme activity 898:905 arg1 levels 788:793 the levels 784:793 the levels of O-GlcNAc-β-catenin, subcellular localization, interaction with binding partners and transcriptional activity of the various constructs 784:931 We determined the levels of O-GlcNAc-β-catenin, subcellular localization, interaction with binding partners and transcriptional activity of the various constructs. 24342833 5 37 theme localization 830:841 arg1 levels 788:793 the levels 784:793 the levels of O-GlcNAc-β-catenin, subcellular localization, interaction with binding partners and transcriptional activity of the various constructs 784:931 We determined the levels of O-GlcNAc-β-catenin, subcellular localization, interaction with binding partners and transcriptional activity of the various constructs. 24342833 5 38 with interaction 844:854 arg1 partners 869:876 binding partners 861:876 binding partners 861:876 We determined the levels of O-GlcNAc-β-catenin, subcellular localization, interaction with binding partners and transcriptional activity of the various constructs. 24342833 1 39 theme single 227:232 arg1 attachment 243:252 a single O-linked attachment 225:252 a single O-linked attachment of β-N-acetyl-glucosamine (O-GlcNAc) 225:289 BACKGROUND: We have previously reported that β-catenin is post-translationally modified with a single O-linked attachment of β-N-acetyl-glucosamine (O-GlcNAc). 24342833 7 40 theme Serine 1183:1188 arg1 O-GlcNAcylation 1164:1178 O-GlcNAcylation 1164:1178 SIGNIFICANCE: O-GlcNAcylation of Serine 23 1150:1191 SIGNIFICANCE: O-GlcNAcylation of Serine 23 is a novel regulatory modification for β-catenin's subcellular localization and transcriptional activity. 24342833 6 41 theme β-catenin 956:964 arg1 Serine 943:948 Serine 23 943:951 Serine 23 of β-catenin 943:964 RESULTS: Serine 23 of β-catenin was determined as a site for O-GlcNAc modification which regulated its subcellular distribution, its interactions with cellular partners and consequently its transcriptional activity. 24342833 6 41 theme β-catenin 956:964 arg1 site 986:989 a site 984:989 a site for O-GlcNAc modification which regulated its subcellular distribution 984:1060 RESULTS: Serine 23 of β-catenin was determined as a site for O-GlcNAc modification which regulated its subcellular distribution, its interactions with cellular partners and consequently its transcriptional activity. 24342833 3 42 theme sites 531:535 arg1 sites 480:484 the putative O-GlcNAc sites 458:484 the putative O-GlcNAc sites of β-catenin 458:497 OBJECTIVE: The objectives of this investigation were to identify the putative O-GlcNAc sites of β-catenin and the relevance of identified sites in the regulation of β-catenin's localization and transcriptional activity. 24342833 3 42 theme sites 531:535 arg1 sites 531:535 identified sites 520:535 identified sites 520:535 OBJECTIVE: The objectives of this investigation were to identify the putative O-GlcNAc sites of β-catenin and the relevance of identified sites in the regulation of β-catenin's localization and transcriptional activity. 24342833 3 42 theme sites 531:535 arg1 β-catenin 489:497 β-catenin 489:497 β-catenin 489:497 OBJECTIVE: The objectives of this investigation were to identify the putative O-GlcNAc sites of β-catenin and the relevance of identified sites in the regulation of β-catenin's localization and transcriptional activity. 24342833 3 42 theme sites 531:535 arg1 relevance 507:515 the relevance 503:515 the relevance of identified sites 503:535 OBJECTIVE: The objectives of this investigation were to identify the putative O-GlcNAc sites of β-catenin and the relevance of identified sites in the regulation of β-catenin's localization and transcriptional activity. 24342833 8 43 theme β-catenin 1374:1382 arg1 regulation 1360:1369 site specific regulation 1346:1369 site specific regulation of β-catenin by the O-GlcNAc modification 1346:1411 This study is the first report to characterize site specific regulation of β-catenin by the O-GlcNAc modification. 24342833 0 44 gly glycosylated 22:33 arg1 β-catenin 0:8 β-catenin 0:8 β-catenin 0:8 β-catenin is O-GlcNAc glycosylated at Serine 23: implications for β-catenin's subcellular localization and transactivator function. 24342833 0 44 gly glycosylated 22:33 arg2 Serine 38:43 Serine 23 38:46 Serine 23 38:46 β-catenin is O-GlcNAc glycosylated at Serine 23: implications for β-catenin's subcellular localization and transactivator function. 24342833 2 45 theme transcriptional 367:381 arg1 activity 383:390 transcriptional activity 367:390 transcriptional activity 367:390 We showed that O-GlcNAc regulated β-catenin's subcellular localization and transcriptional activity. 24342833 6 46 theme subcellular 1037:1047 arg1 distribution 1049:1060 its subcellular distribution 1033:1060 its subcellular distribution 1033:1060 RESULTS: Serine 23 of β-catenin was determined as a site for O-GlcNAc modification which regulated its subcellular distribution, its interactions with cellular partners and consequently its transcriptional activity. 24342833 6 47 with activity 1140:1147 arg1 partners 1094:1101 cellular partners 1085:1101 cellular partners 1085:1101 RESULTS: Serine 23 of β-catenin was determined as a site for O-GlcNAc modification which regulated its subcellular distribution, its interactions with cellular partners and consequently its transcriptional activity. 24342833 1 48 theme O-linked 234:241 arg1 attachment 243:252 a single O-linked attachment 225:252 a single O-linked attachment of β-N-acetyl-glucosamine (O-GlcNAc) 225:289 BACKGROUND: We have previously reported that β-catenin is post-translationally modified with a single O-linked attachment of β-N-acetyl-glucosamine (O-GlcNAc). 24342833 5 49 with activity 898:905 arg1 partners 869:876 binding partners 861:876 binding partners 861:876 We determined the levels of O-GlcNAc-β-catenin, subcellular localization, interaction with binding partners and transcriptional activity of the various constructs. 24342833 3 50 theme identified 520:529 arg1 sites 531:535 identified sites 520:535 identified sites 520:535 OBJECTIVE: The objectives of this investigation were to identify the putative O-GlcNAc sites of β-catenin and the relevance of identified sites in the regulation of β-catenin's localization and transcriptional activity. 24342833 5 51 with O-GlcNAc-β-catenin 798:815 arg1 partners 869:876 binding partners 861:876 binding partners 861:876 We determined the levels of O-GlcNAc-β-catenin, subcellular localization, interaction with binding partners and transcriptional activity of the various constructs. 24342833 5 52 theme binding 861:867 arg1 partners 869:876 binding partners 861:876 binding partners 861:876 We determined the levels of O-GlcNAc-β-catenin, subcellular localization, interaction with binding partners and transcriptional activity of the various constructs. 24342833 1 53 theme β-N-acetyl-glucosamine 257:278 arg1 attachment 243:252 a single O-linked attachment 225:252 a single O-linked attachment of β-N-acetyl-glucosamine (O-GlcNAc) 225:289 BACKGROUND: We have previously reported that β-catenin is post-translationally modified with a single O-linked attachment of β-N-acetyl-glucosamine (O-GlcNAc). 24342833 4 54 theme potential 659:667 arg1 Type-β-catenin 725:738 pEGFP-C2-N-Terminal- or pEGFP-C2-Wild Type-β-catenin 687:738 pEGFP-C2-N-Terminal- or pEGFP-C2-Wild Type-β-catenin 687:738 METHOD: Missense mutations were introduced to potential O-GlcNAc sites of pEGFP-C2-N-Terminal- or pEGFP-C2-Wild Type-β-catenin by site-directed mutagenesis. 24342833 4 54 theme potential 659:667 arg1 sites 678:682 potential O-GlcNAc sites 659:682 potential O-GlcNAc sites of pEGFP-C2-N-Terminal- or pEGFP-C2-Wild Type-β-catenin 659:738 METHOD: Missense mutations were introduced to potential O-GlcNAc sites of pEGFP-C2-N-Terminal- or pEGFP-C2-Wild Type-β-catenin by site-directed mutagenesis. 24342833 4 55 theme O-GlcNAc 669:676 arg1 Type-β-catenin 725:738 pEGFP-C2-N-Terminal- or pEGFP-C2-Wild Type-β-catenin 687:738 pEGFP-C2-N-Terminal- or pEGFP-C2-Wild Type-β-catenin 687:738 METHOD: Missense mutations were introduced to potential O-GlcNAc sites of pEGFP-C2-N-Terminal- or pEGFP-C2-Wild Type-β-catenin by site-directed mutagenesis. 24342833 4 55 theme O-GlcNAc 669:676 arg1 sites 678:682 potential O-GlcNAc sites 659:682 potential O-GlcNAc sites of pEGFP-C2-N-Terminal- or pEGFP-C2-Wild Type-β-catenin 659:738 METHOD: Missense mutations were introduced to potential O-GlcNAc sites of pEGFP-C2-N-Terminal- or pEGFP-C2-Wild Type-β-catenin by site-directed mutagenesis. 28512128 0 0 theme complex 89:95 arg1 subunit 48:54 the STT3/Stt3 protein subunit 26:54 the STT3/Stt3 protein subunit of the oligosaccharyltransferase complex 26:95 Refined topology model of the STT3/Stt3 protein subunit of the oligosaccharyltransferase complex. 28512128 5 1 theme integration 784:794 arg1 efficiency 796:805 the membrane integration efficiency 771:805 the membrane integration efficiency of the mouse STT3-A 771:825 We measured the membrane integration efficiency of the mouse STT3-A and yeast Stt3p transmembrane domains (TMDs) and report a refined topology of the N-terminal half of the mouse STT3-A. 28512128 4 2 theme mapping 710:716 arg1 approach 718:725 a glycosylation mapping approach 694:725 a glycosylation mapping approach 694:725 Here, we use a glycosylation mapping approach to investigate these questions. 28512128 1 3 theme numerous 251:258 arg1 substrates 268:277 numerous protein substrates 251:277 numerous protein substrates 251:277 The oligosaccharyltransferase complex, localized in the endoplasmic reticulum (ER) of eukaryotic cells, is responsible for the N-linked glycosylation of numerous protein substrates. 28512128 0 4 theme oligosaccharyltransferase 63:87 arg1 complex 89:95 the oligosaccharyltransferase complex 59:95 the oligosaccharyltransferase complex 59:95 Refined topology model of the STT3/Stt3 protein subunit of the oligosaccharyltransferase complex. 28512128 9 5 with consistent 1471:1480 arg1 structure 1491:1499 the structure 1487:1499 the structure of the bacterial homolog of STT3 1487:1532 This result indicates that the eukaryotic STT3 has 13 transmembrane domains, consistent with the structure of the bacterial homolog of STT3 and setting the stage for future combined efforts to interrogate this fascinating system. 28512128 4 6 theme glycosylation 696:708 arg1 approach 718:725 a glycosylation mapping approach 694:725 a glycosylation mapping approach 694:725 Here, we use a glycosylation mapping approach to investigate these questions. 28512128 1 7 theme protein 260:266 arg1 substrates 268:277 numerous protein substrates 251:277 numerous protein substrates 251:277 The oligosaccharyltransferase complex, localized in the endoplasmic reticulum (ER) of eukaryotic cells, is responsible for the N-linked glycosylation of numerous protein substrates. 28512128 7 8 dep domains 1137:1143 arg1 2 1177:1177 2 1177:1177 2 1177:1177 However, for the mouse STT3-A hydrophobic domains 4 and 6 and yeast Stt3p domains 2, 3a, 3c, and 6 we measured reduced insertion efficiency into the ER membrane. 28512128 7 8 dep domains 1137:1143 arg1 6 1151:1151 6 1151:1151 6 1151:1151 However, for the mouse STT3-A hydrophobic domains 4 and 6 and yeast Stt3p domains 2, 3a, 3c, and 6 we measured reduced insertion efficiency into the ER membrane. 28512128 7 8 dep domains 1137:1143 arg1 4 1145:1145 4 1145:1145 4 1145:1145 However, for the mouse STT3-A hydrophobic domains 4 and 6 and yeast Stt3p domains 2, 3a, 3c, and 6 we measured reduced insertion efficiency into the ER membrane. 28512128 5 9 theme mouse 814:818 arg1 STT3-A 820:825 the mouse STT3-A 810:825 the mouse STT3-A 810:825 We measured the membrane integration efficiency of the mouse STT3-A and yeast Stt3p transmembrane domains (TMDs) and report a refined topology of the N-terminal half of the mouse STT3-A. 28512128 1 10 theme substrates 268:277 arg1 glycosylation 234:246 the N-linked glycosylation 221:246 the N-linked glycosylation of numerous protein substrates 221:277 The oligosaccharyltransferase complex, localized in the endoplasmic reticulum (ER) of eukaryotic cells, is responsible for the N-linked glycosylation of numerous protein substrates. 28512128 5 11 theme STT3-A 938:943 arg1 half 920:923 the N-terminal half 905:923 the N-terminal half of the mouse STT3-A 905:943 We measured the membrane integration efficiency of the mouse STT3-A and yeast Stt3p transmembrane domains (TMDs) and report a refined topology of the N-terminal half of the mouse STT3-A. 28512128 3 12 theme structural 545:554 arg1 topology 556:563 the structural topology 541:563 the structural topology of the bacterial versus eukaryotic proteins 541:607 However, understanding the catalytic determinants of this system has been challenging, in part because of a discrepancy in the structural topology of the bacterial versus eukaryotic proteins and incomplete information about the mechanism of membrane integration. 28512128 2 13 theme protein 293:299 arg1 part 328:331 a highly conserved part 309:331 a highly conserved part of the oligosaccharyltransferase 309:364 The membrane protein STT3 is a highly conserved part of the oligosaccharyltransferase and likely contains the active site of the complex. 28512128 2 13 theme protein 293:299 arg1 STT3 301:304 The membrane protein STT3 280:304 The membrane protein STT3 280:304 The membrane protein STT3 is a highly conserved part of the oligosaccharyltransferase and likely contains the active site of the complex. 28512128 6 14 theme flanking 1076:1083 arg1 residues 1085:1092 the natural flanking residues 1064:1092 the natural flanking residues 1064:1092 Our results show that most of the STT3 TMDs are well inserted into the ER membrane on their own or in the presence of the natural flanking residues. 28512128 5 15 theme half 920:923 arg1 topology 893:900 a refined topology 883:900 a refined topology of the N-terminal half of the mouse STT3-A 883:943 We measured the membrane integration efficiency of the mouse STT3-A and yeast Stt3p transmembrane domains (TMDs) and report a refined topology of the N-terminal half of the mouse STT3-A. 28512128 9 16 theme future 1560:1565 arg1 efforts 1576:1582 future combined efforts 1560:1582 future combined efforts 1560:1582 This result indicates that the eukaryotic STT3 has 13 transmembrane domains, consistent with the structure of the bacterial homolog of STT3 and setting the stage for future combined efforts to interrogate this fascinating system. 28512128 1 17 gly glycosylation 234:246 arg1 substrates 268:277 numerous protein substrates 251:277 numerous protein substrates 251:277 The oligosaccharyltransferase complex, localized in the endoplasmic reticulum (ER) of eukaryotic cells, is responsible for the N-linked glycosylation of numerous protein substrates. 28512128 2 18 theme membrane 284:291 arg1 part 328:331 a highly conserved part 309:331 a highly conserved part of the oligosaccharyltransferase 309:364 The membrane protein STT3 is a highly conserved part of the oligosaccharyltransferase and likely contains the active site of the complex. 28512128 2 18 theme membrane 284:291 arg1 STT3 301:304 The membrane protein STT3 280:304 The membrane protein STT3 280:304 The membrane protein STT3 is a highly conserved part of the oligosaccharyltransferase and likely contains the active site of the complex. 28512128 3 19 from information 624:634 arg1 topology 556:563 the structural topology 541:563 the structural topology of the bacterial versus eukaryotic proteins 541:607 However, understanding the catalytic determinants of this system has been challenging, in part because of a discrepancy in the structural topology of the bacterial versus eukaryotic proteins and incomplete information about the mechanism of membrane integration. 28512128 3 20 theme catalytic 445:453 arg1 determinants 455:466 the catalytic determinants 441:466 the catalytic determinants of this system 441:481 However, understanding the catalytic determinants of this system has been challenging, in part because of a discrepancy in the structural topology of the bacterial versus eukaryotic proteins and incomplete information about the mechanism of membrane integration. 28512128 5 21 theme STT3-A 820:825 arg1 TMDs 866:869 TMDs 866:869 TMDs 866:869 We measured the membrane integration efficiency of the mouse STT3-A and yeast Stt3p transmembrane domains (TMDs) and report a refined topology of the N-terminal half of the mouse STT3-A. 28512128 5 21 theme STT3-A 820:825 arg1 domains 857:863 yeast Stt3p transmembrane domains 831:863 yeast Stt3p transmembrane domains (TMDs) 831:870 We measured the membrane integration efficiency of the mouse STT3-A and yeast Stt3p transmembrane domains (TMDs) and report a refined topology of the N-terminal half of the mouse STT3-A. 28512128 5 21 theme STT3-A 820:825 arg1 STT3-A 820:825 the mouse STT3-A 810:825 the mouse STT3-A 810:825 We measured the membrane integration efficiency of the mouse STT3-A and yeast Stt3p transmembrane domains (TMDs) and report a refined topology of the N-terminal half of the mouse STT3-A. 28512128 5 21 theme STT3-A 820:825 arg1 efficiency 796:805 the membrane integration efficiency 771:805 the membrane integration efficiency of the mouse STT3-A 771:825 We measured the membrane integration efficiency of the mouse STT3-A and yeast Stt3p transmembrane domains (TMDs) and report a refined topology of the N-terminal half of the mouse STT3-A. 28512128 2 22 contain contains 377:384 arg1 part 328:331 a highly conserved part 309:331 a highly conserved part of the oligosaccharyltransferase 309:364 The membrane protein STT3 is a highly conserved part of the oligosaccharyltransferase and likely contains the active site of the complex. 28512128 2 22 contain contains 377:384 arg1 STT3 301:304 The membrane protein STT3 280:304 The membrane protein STT3 280:304 The membrane protein STT3 is a highly conserved part of the oligosaccharyltransferase and likely contains the active site of the complex. 28512128 2 22 contain contains 377:384 arg2 complex 409:415 the complex 405:415 the complex 405:415 The membrane protein STT3 is a highly conserved part of the oligosaccharyltransferase and likely contains the active site of the complex. 28512128 2 22 contain contains 377:384 arg2 site 397:400 the active site 386:400 the active site of the complex 386:415 The membrane protein STT3 is a highly conserved part of the oligosaccharyltransferase and likely contains the active site of the complex. 28512128 9 23 theme combined 1567:1574 arg1 efforts 1576:1582 future combined efforts 1560:1582 future combined efforts 1560:1582 This result indicates that the eukaryotic STT3 has 13 transmembrane domains, consistent with the structure of the bacterial homolog of STT3 and setting the stage for future combined efforts to interrogate this fascinating system. 28512128 6 24 from membrane 1020:1027 arg1 presence 1052:1059 the presence 1048:1059 the presence of the natural flanking residues 1048:1092 Our results show that most of the STT3 TMDs are well inserted into the ER membrane on their own or in the presence of the natural flanking residues. 28512128 6 24 from membrane 1020:1027 arg1 own 1038:1040 own 1038:1040 own 1038:1040 Our results show that most of the STT3 TMDs are well inserted into the ER membrane on their own or in the presence of the natural flanking residues. 28512128 5 25 theme yeast 831:835 arg1 TMDs 866:869 TMDs 866:869 TMDs 866:869 We measured the membrane integration efficiency of the mouse STT3-A and yeast Stt3p transmembrane domains (TMDs) and report a refined topology of the N-terminal half of the mouse STT3-A. 28512128 5 25 theme yeast 831:835 arg1 domains 857:863 yeast Stt3p transmembrane domains 831:863 yeast Stt3p transmembrane domains (TMDs) 831:870 We measured the membrane integration efficiency of the mouse STT3-A and yeast Stt3p transmembrane domains (TMDs) and report a refined topology of the N-terminal half of the mouse STT3-A. 28512128 5 25 theme yeast 831:835 arg1 STT3-A 820:825 the mouse STT3-A 810:825 the mouse STT3-A 810:825 We measured the membrane integration efficiency of the mouse STT3-A and yeast Stt3p transmembrane domains (TMDs) and report a refined topology of the N-terminal half of the mouse STT3-A. 28512128 9 26 theme bacterial 1508:1516 arg1 homolog 1518:1524 the bacterial homolog 1504:1524 the bacterial homolog of STT3 1504:1532 This result indicates that the eukaryotic STT3 has 13 transmembrane domains, consistent with the structure of the bacterial homolog of STT3 and setting the stage for future combined efforts to interrogate this fascinating system. 28512128 0 27 theme topology 8:15 arg1 model 17:21 Refined topology model 0:21 Refined topology model of the STT3/Stt3 protein subunit of the oligosaccharyltransferase complex 0:95 Refined topology model of the STT3/Stt3 protein subunit of the oligosaccharyltransferase complex. 28512128 9 28 contain has 1441:1443 arg2 domains 1462:1468 13 transmembrane domains 1445:1468 13 transmembrane domains 1445:1468 This result indicates that the eukaryotic STT3 has 13 transmembrane domains, consistent with the structure of the bacterial homolog of STT3 and setting the stage for future combined efforts to interrogate this fascinating system. 28512128 9 28 contain has 1441:1443 arg1 STT3 1436:1439 the eukaryotic STT3 1421:1439 the eukaryotic STT3 1421:1439 This result indicates that the eukaryotic STT3 has 13 transmembrane domains, consistent with the structure of the bacterial homolog of STT3 and setting the stage for future combined efforts to interrogate this fascinating system. 28512128 9 29 theme eukaryotic 1425:1434 arg1 STT3 1436:1439 the eukaryotic STT3 1421:1439 the eukaryotic STT3 1421:1439 This result indicates that the eukaryotic STT3 has 13 transmembrane domains, consistent with the structure of the bacterial homolog of STT3 and setting the stage for future combined efforts to interrogate this fascinating system. 28512128 2 30 theme conserved 318:326 arg1 part 328:331 a highly conserved part 309:331 a highly conserved part of the oligosaccharyltransferase 309:364 The membrane protein STT3 is a highly conserved part of the oligosaccharyltransferase and likely contains the active site of the complex. 28512128 2 30 theme conserved 318:326 arg1 STT3 301:304 The membrane protein STT3 280:304 The membrane protein STT3 280:304 The membrane protein STT3 is a highly conserved part of the oligosaccharyltransferase and likely contains the active site of the complex. 28512128 1 31 theme eukaryotic 184:193 arg1 cells 195:199 eukaryotic cells 184:199 eukaryotic cells 184:199 The oligosaccharyltransferase complex, localized in the endoplasmic reticulum (ER) of eukaryotic cells, is responsible for the N-linked glycosylation of numerous protein substrates. 28512128 0 32 theme Refined 0:6 arg1 model 17:21 Refined topology model 0:21 Refined topology model of the STT3/Stt3 protein subunit of the oligosaccharyltransferase complex 0:95 Refined topology model of the STT3/Stt3 protein subunit of the oligosaccharyltransferase complex. 28512128 8 33 theme fourth 1382:1387 arg1 TMD 1389:1391 the fourth TMD 1378:1391 the fourth TMD 1378:1391 Furthermore, we mapped the first half of the STT3-A protein, finding two extra hydrophobic domains between the third and the fourth TMD. 28512128 3 34 theme bacterial 572:580 arg1 proteins 600:607 the bacterial versus eukaryotic proteins 568:607 the bacterial versus eukaryotic proteins 568:607 However, understanding the catalytic determinants of this system has been challenging, in part because of a discrepancy in the structural topology of the bacterial versus eukaryotic proteins and incomplete information about the mechanism of membrane integration. 28512128 1 35 theme cells 195:199 arg1 reticulum 166:174 the endoplasmic reticulum 150:174 the endoplasmic reticulum (ER) of eukaryotic cells 150:199 The oligosaccharyltransferase complex, localized in the endoplasmic reticulum (ER) of eukaryotic cells, is responsible for the N-linked glycosylation of numerous protein substrates. 28512128 1 35 theme cells 195:199 arg1 ER 177:178 ER 177:178 ER 177:178 The oligosaccharyltransferase complex, localized in the endoplasmic reticulum (ER) of eukaryotic cells, is responsible for the N-linked glycosylation of numerous protein substrates. 28512128 5 36 theme Stt3p 837:841 arg1 TMDs 866:869 TMDs 866:869 TMDs 866:869 We measured the membrane integration efficiency of the mouse STT3-A and yeast Stt3p transmembrane domains (TMDs) and report a refined topology of the N-terminal half of the mouse STT3-A. 28512128 5 36 theme Stt3p 837:841 arg1 domains 857:863 yeast Stt3p transmembrane domains 831:863 yeast Stt3p transmembrane domains (TMDs) 831:870 We measured the membrane integration efficiency of the mouse STT3-A and yeast Stt3p transmembrane domains (TMDs) and report a refined topology of the N-terminal half of the mouse STT3-A. 28512128 5 36 theme Stt3p 837:841 arg1 STT3-A 820:825 the mouse STT3-A 810:825 the mouse STT3-A 810:825 We measured the membrane integration efficiency of the mouse STT3-A and yeast Stt3p transmembrane domains (TMDs) and report a refined topology of the N-terminal half of the mouse STT3-A. 28512128 8 37 theme hydrophobic 1336:1346 arg1 domains 1348:1354 two extra hydrophobic domains 1326:1354 two extra hydrophobic domains between the third and the fourth TMD 1326:1391 Furthermore, we mapped the first half of the STT3-A protein, finding two extra hydrophobic domains between the third and the fourth TMD. 28512128 1 38 link N-linked 225:232 arg1 glycosylation 234:246 the N-linked glycosylation 221:246 the N-linked glycosylation of numerous protein substrates 221:277 The oligosaccharyltransferase complex, localized in the endoplasmic reticulum (ER) of eukaryotic cells, is responsible for the N-linked glycosylation of numerous protein substrates. 28512128 1 39 theme oligosaccharyltransferase 102:126 arg1 responsible 205:215 responsible 205:215 responsible 205:215 The oligosaccharyltransferase complex, localized in the endoplasmic reticulum (ER) of eukaryotic cells, is responsible for the N-linked glycosylation of numerous protein substrates. 28512128 1 39 theme oligosaccharyltransferase 102:126 arg1 complex 128:134 The oligosaccharyltransferase complex 98:134 The oligosaccharyltransferase complex 98:134 The oligosaccharyltransferase complex, localized in the endoplasmic reticulum (ER) of eukaryotic cells, is responsible for the N-linked glycosylation of numerous protein substrates. 28512128 8 40 theme STT3-A 1302:1307 arg1 protein 1309:1315 the STT3-A protein 1298:1315 the STT3-A protein 1298:1315 Furthermore, we mapped the first half of the STT3-A protein, finding two extra hydrophobic domains between the third and the fourth TMD. 28512128 3 41 theme system 476:481 arg1 determinants 455:466 the catalytic determinants 441:466 the catalytic determinants of this system 441:481 However, understanding the catalytic determinants of this system has been challenging, in part because of a discrepancy in the structural topology of the bacterial versus eukaryotic proteins and incomplete information about the mechanism of membrane integration. 28512128 5 42 theme transmembrane 843:855 arg1 TMDs 866:869 TMDs 866:869 TMDs 866:869 We measured the membrane integration efficiency of the mouse STT3-A and yeast Stt3p transmembrane domains (TMDs) and report a refined topology of the N-terminal half of the mouse STT3-A. 28512128 5 42 theme transmembrane 843:855 arg1 domains 857:863 yeast Stt3p transmembrane domains 831:863 yeast Stt3p transmembrane domains (TMDs) 831:870 We measured the membrane integration efficiency of the mouse STT3-A and yeast Stt3p transmembrane domains (TMDs) and report a refined topology of the N-terminal half of the mouse STT3-A. 28512128 5 42 theme transmembrane 843:855 arg1 STT3-A 820:825 the mouse STT3-A 810:825 the mouse STT3-A 810:825 We measured the membrane integration efficiency of the mouse STT3-A and yeast Stt3p transmembrane domains (TMDs) and report a refined topology of the N-terminal half of the mouse STT3-A. 28512128 9 43 theme transmembrane 1448:1460 arg1 domains 1462:1468 13 transmembrane domains 1445:1468 13 transmembrane domains 1445:1468 This result indicates that the eukaryotic STT3 has 13 transmembrane domains, consistent with the structure of the bacterial homolog of STT3 and setting the stage for future combined efforts to interrogate this fascinating system. 28512128 3 44 theme membrane 659:666 arg1 integration 668:678 membrane integration 659:678 membrane integration 659:678 However, understanding the catalytic determinants of this system has been challenging, in part because of a discrepancy in the structural topology of the bacterial versus eukaryotic proteins and incomplete information about the mechanism of membrane integration. 28512128 5 45 theme N-terminal 909:918 arg1 half 920:923 the N-terminal half 905:923 the N-terminal half of the mouse STT3-A 905:943 We measured the membrane integration efficiency of the mouse STT3-A and yeast Stt3p transmembrane domains (TMDs) and report a refined topology of the N-terminal half of the mouse STT3-A. 28512128 6 46 theme natural 1068:1074 arg1 residues 1085:1092 the natural flanking residues 1064:1092 the natural flanking residues 1064:1092 Our results show that most of the STT3 TMDs are well inserted into the ER membrane on their own or in the presence of the natural flanking residues. 28512128 0 47 theme STT3/Stt3 30:38 arg1 subunit 48:54 the STT3/Stt3 protein subunit 26:54 the STT3/Stt3 protein subunit of the oligosaccharyltransferase complex 26:95 Refined topology model of the STT3/Stt3 protein subunit of the oligosaccharyltransferase complex. 28512128 7 48 theme insertion 1214:1222 arg1 efficiency 1224:1233 reduced insertion efficiency 1206:1233 reduced insertion efficiency 1206:1233 However, for the mouse STT3-A hydrophobic domains 4 and 6 and yeast Stt3p domains 2, 3a, 3c, and 6 we measured reduced insertion efficiency into the ER membrane. 28512128 9 49 theme fascinating 1604:1614 arg1 system 1616:1621 this fascinating system 1599:1621 this fascinating system 1599:1621 This result indicates that the eukaryotic STT3 has 13 transmembrane domains, consistent with the structure of the bacterial homolog of STT3 and setting the stage for future combined efforts to interrogate this fascinating system. 28512128 3 50 theme integration 668:678 arg1 mechanism 646:654 the mechanism 642:654 the mechanism of membrane integration 642:678 However, understanding the catalytic determinants of this system has been challenging, in part because of a discrepancy in the structural topology of the bacterial versus eukaryotic proteins and incomplete information about the mechanism of membrane integration. 28512128 3 51 theme proteins 600:607 arg1 topology 556:563 the structural topology 541:563 the structural topology of the bacterial versus eukaryotic proteins 541:607 However, understanding the catalytic determinants of this system has been challenging, in part because of a discrepancy in the structural topology of the bacterial versus eukaryotic proteins and incomplete information about the mechanism of membrane integration. 28512128 2 52 theme active 390:395 arg1 site 397:400 the active site 386:400 the active site of the complex 386:415 The membrane protein STT3 is a highly conserved part of the oligosaccharyltransferase and likely contains the active site of the complex. 28512128 2 52 theme active 390:395 arg1 complex 409:415 the complex 405:415 the complex 405:415 The membrane protein STT3 is a highly conserved part of the oligosaccharyltransferase and likely contains the active site of the complex. 28512128 7 53 theme reduced 1206:1212 arg1 efficiency 1224:1233 reduced insertion efficiency 1206:1233 reduced insertion efficiency 1206:1233 However, for the mouse STT3-A hydrophobic domains 4 and 6 and yeast Stt3p domains 2, 3a, 3c, and 6 we measured reduced insertion efficiency into the ER membrane. 28512128 7 54 theme mouse 1112:1116 arg1 3c 1184:1185 3c 1184:1185 3c 1184:1185 However, for the mouse STT3-A hydrophobic domains 4 and 6 and yeast Stt3p domains 2, 3a, 3c, and 6 we measured reduced insertion efficiency into the ER membrane. 28512128 7 54 theme mouse 1112:1116 arg1 6 1192:1192 6 1192:1192 6 1192:1192 However, for the mouse STT3-A hydrophobic domains 4 and 6 and yeast Stt3p domains 2, 3a, 3c, and 6 we measured reduced insertion efficiency into the ER membrane. 28512128 7 54 theme mouse 1112:1116 arg1 3a 1180:1181 3a 1180:1181 3a 1180:1181 However, for the mouse STT3-A hydrophobic domains 4 and 6 and yeast Stt3p domains 2, 3a, 3c, and 6 we measured reduced insertion efficiency into the ER membrane. 28512128 7 54 theme mouse 1112:1116 arg1 domains 1137:1143 the mouse STT3-A hydrophobic domains 4 and 6 1108:1151 the mouse STT3-A hydrophobic domains 4 and 6 1108:1151 However, for the mouse STT3-A hydrophobic domains 4 and 6 and yeast Stt3p domains 2, 3a, 3c, and 6 we measured reduced insertion efficiency into the ER membrane. 28512128 7 55 theme STT3-A 1118:1123 arg1 3c 1184:1185 3c 1184:1185 3c 1184:1185 However, for the mouse STT3-A hydrophobic domains 4 and 6 and yeast Stt3p domains 2, 3a, 3c, and 6 we measured reduced insertion efficiency into the ER membrane. 28512128 7 55 theme STT3-A 1118:1123 arg1 6 1192:1192 6 1192:1192 6 1192:1192 However, for the mouse STT3-A hydrophobic domains 4 and 6 and yeast Stt3p domains 2, 3a, 3c, and 6 we measured reduced insertion efficiency into the ER membrane. 28512128 7 55 theme STT3-A 1118:1123 arg1 3a 1180:1181 3a 1180:1181 3a 1180:1181 However, for the mouse STT3-A hydrophobic domains 4 and 6 and yeast Stt3p domains 2, 3a, 3c, and 6 we measured reduced insertion efficiency into the ER membrane. 28512128 7 55 theme STT3-A 1118:1123 arg1 domains 1137:1143 the mouse STT3-A hydrophobic domains 4 and 6 1108:1151 the mouse STT3-A hydrophobic domains 4 and 6 1108:1151 However, for the mouse STT3-A hydrophobic domains 4 and 6 and yeast Stt3p domains 2, 3a, 3c, and 6 we measured reduced insertion efficiency into the ER membrane. 28512128 9 56 theme STT3 1529:1532 arg1 homolog 1518:1524 the bacterial homolog 1504:1524 the bacterial homolog of STT3 1504:1532 This result indicates that the eukaryotic STT3 has 13 transmembrane domains, consistent with the structure of the bacterial homolog of STT3 and setting the stage for future combined efforts to interrogate this fascinating system. 28512128 2 57 theme complex 409:415 arg1 site 397:400 the active site 386:400 the active site of the complex 386:415 The membrane protein STT3 is a highly conserved part of the oligosaccharyltransferase and likely contains the active site of the complex. 28512128 2 57 theme complex 409:415 arg1 complex 409:415 the complex 405:415 the complex 405:415 The membrane protein STT3 is a highly conserved part of the oligosaccharyltransferase and likely contains the active site of the complex. 28512128 0 58 theme subunit 48:54 arg1 model 17:21 Refined topology model 0:21 Refined topology model of the STT3/Stt3 protein subunit of the oligosaccharyltransferase complex 0:95 Refined topology model of the STT3/Stt3 protein subunit of the oligosaccharyltransferase complex. 28512128 8 59 theme first 1284:1288 arg1 half 1290:1293 the first half 1280:1293 the first half of the STT3-A protein 1280:1315 Furthermore, we mapped the first half of the STT3-A protein, finding two extra hydrophobic domains between the third and the fourth TMD. 28512128 2 60 theme oligosaccharyltransferase 340:364 arg1 part 328:331 a highly conserved part 309:331 a highly conserved part of the oligosaccharyltransferase 309:364 The membrane protein STT3 is a highly conserved part of the oligosaccharyltransferase and likely contains the active site of the complex. 28512128 2 60 theme oligosaccharyltransferase 340:364 arg1 STT3 301:304 The membrane protein STT3 280:304 The membrane protein STT3 280:304 The membrane protein STT3 is a highly conserved part of the oligosaccharyltransferase and likely contains the active site of the complex. 28512128 0 61 theme protein 40:46 arg1 subunit 48:54 the STT3/Stt3 protein subunit 26:54 the STT3/Stt3 protein subunit of the oligosaccharyltransferase complex 26:95 Refined topology model of the STT3/Stt3 protein subunit of the oligosaccharyltransferase complex. 28512128 7 62 theme ER 1244:1245 arg1 membrane 1247:1254 the ER membrane 1240:1254 the ER membrane 1240:1254 However, for the mouse STT3-A hydrophobic domains 4 and 6 and yeast Stt3p domains 2, 3a, 3c, and 6 we measured reduced insertion efficiency into the ER membrane. 28512128 3 63 theme eukaryotic 589:598 arg1 proteins 600:607 the bacterial versus eukaryotic proteins 568:607 the bacterial versus eukaryotic proteins 568:607 However, understanding the catalytic determinants of this system has been challenging, in part because of a discrepancy in the structural topology of the bacterial versus eukaryotic proteins and incomplete information about the mechanism of membrane integration. 28512128 8 64 theme extra 1330:1334 arg1 domains 1348:1354 two extra hydrophobic domains 1326:1354 two extra hydrophobic domains between the third and the fourth TMD 1326:1391 Furthermore, we mapped the first half of the STT3-A protein, finding two extra hydrophobic domains between the third and the fourth TMD. 28512128 9 65 theme homolog 1518:1524 arg1 structure 1491:1499 the structure 1487:1499 the structure of the bacterial homolog of STT3 1487:1532 This result indicates that the eukaryotic STT3 has 13 transmembrane domains, consistent with the structure of the bacterial homolog of STT3 and setting the stage for future combined efforts to interrogate this fascinating system. 28512128 6 66 theme residues 1085:1092 arg1 presence 1052:1059 the presence 1048:1059 the presence of the natural flanking residues 1048:1092 Our results show that most of the STT3 TMDs are well inserted into the ER membrane on their own or in the presence of the natural flanking residues. 28512128 5 67 theme refined 885:891 arg1 topology 893:900 a refined topology 883:900 a refined topology of the N-terminal half of the mouse STT3-A 883:943 We measured the membrane integration efficiency of the mouse STT3-A and yeast Stt3p transmembrane domains (TMDs) and report a refined topology of the N-terminal half of the mouse STT3-A. 28512128 6 68 theme STT3 980:983 arg1 TMDs 985:988 the STT3 TMDs 976:988 the STT3 TMDs 976:988 Our results show that most of the STT3 TMDs are well inserted into the ER membrane on their own or in the presence of the natural flanking residues. 28512128 7 69 theme Stt3p 1163:1167 arg1 domains 1169:1175 yeast Stt3p domains 1157:1175 yeast Stt3p domains 1157:1175 However, for the mouse STT3-A hydrophobic domains 4 and 6 and yeast Stt3p domains 2, 3a, 3c, and 6 we measured reduced insertion efficiency into the ER membrane. 28512128 5 70 theme mouse 932:936 arg1 STT3-A 938:943 the mouse STT3-A 928:943 the mouse STT3-A 928:943 We measured the membrane integration efficiency of the mouse STT3-A and yeast Stt3p transmembrane domains (TMDs) and report a refined topology of the N-terminal half of the mouse STT3-A. 28512128 1 71 theme N-linked 225:232 arg1 glycosylation 234:246 the N-linked glycosylation 221:246 the N-linked glycosylation of numerous protein substrates 221:277 The oligosaccharyltransferase complex, localized in the endoplasmic reticulum (ER) of eukaryotic cells, is responsible for the N-linked glycosylation of numerous protein substrates. 28512128 8 72 theme protein 1309:1315 arg1 half 1290:1293 the first half 1280:1293 the first half of the STT3-A protein 1280:1315 Furthermore, we mapped the first half of the STT3-A protein, finding two extra hydrophobic domains between the third and the fourth TMD. 28512128 6 73 theme ER 1017:1018 arg1 membrane 1020:1027 the ER membrane 1013:1027 the ER membrane on their own or in the presence of the natural flanking residues 1013:1092 Our results show that most of the STT3 TMDs are well inserted into the ER membrane on their own or in the presence of the natural flanking residues. 28512128 3 74 theme incomplete 613:622 arg1 information 624:634 incomplete information 613:634 incomplete information about the mechanism of membrane integration 613:678 However, understanding the catalytic determinants of this system has been challenging, in part because of a discrepancy in the structural topology of the bacterial versus eukaryotic proteins and incomplete information about the mechanism of membrane integration. 28512128 1 75 theme endoplasmic 154:164 arg1 reticulum 166:174 the endoplasmic reticulum 150:174 the endoplasmic reticulum (ER) of eukaryotic cells 150:199 The oligosaccharyltransferase complex, localized in the endoplasmic reticulum (ER) of eukaryotic cells, is responsible for the N-linked glycosylation of numerous protein substrates. 28512128 1 75 theme endoplasmic 154:164 arg1 ER 177:178 ER 177:178 ER 177:178 The oligosaccharyltransferase complex, localized in the endoplasmic reticulum (ER) of eukaryotic cells, is responsible for the N-linked glycosylation of numerous protein substrates. 28512128 5 76 theme membrane 775:782 arg1 efficiency 796:805 the membrane integration efficiency 771:805 the membrane integration efficiency of the mouse STT3-A 771:825 We measured the membrane integration efficiency of the mouse STT3-A and yeast Stt3p transmembrane domains (TMDs) and report a refined topology of the N-terminal half of the mouse STT3-A. 28512128 1 77 located localized 137:145 arg2 complex 128:134 The oligosaccharyltransferase complex 98:134 The oligosaccharyltransferase complex 98:134 The oligosaccharyltransferase complex, localized in the endoplasmic reticulum (ER) of eukaryotic cells, is responsible for the N-linked glycosylation of numerous protein substrates. 28512128 1 77 located localized 137:145 arg1 reticulum 166:174 the endoplasmic reticulum 150:174 the endoplasmic reticulum (ER) of eukaryotic cells 150:199 The oligosaccharyltransferase complex, localized in the endoplasmic reticulum (ER) of eukaryotic cells, is responsible for the N-linked glycosylation of numerous protein substrates. 28512128 1 77 located localized 137:145 arg2 responsible 205:215 responsible 205:215 responsible 205:215 The oligosaccharyltransferase complex, localized in the endoplasmic reticulum (ER) of eukaryotic cells, is responsible for the N-linked glycosylation of numerous protein substrates. 28512128 1 77 located localized 137:145 arg1 ER 177:178 ER 177:178 ER 177:178 The oligosaccharyltransferase complex, localized in the endoplasmic reticulum (ER) of eukaryotic cells, is responsible for the N-linked glycosylation of numerous protein substrates. 28512128 7 78 theme hydrophobic 1125:1135 arg1 3c 1184:1185 3c 1184:1185 3c 1184:1185 However, for the mouse STT3-A hydrophobic domains 4 and 6 and yeast Stt3p domains 2, 3a, 3c, and 6 we measured reduced insertion efficiency into the ER membrane. 28512128 7 78 theme hydrophobic 1125:1135 arg1 6 1192:1192 6 1192:1192 6 1192:1192 However, for the mouse STT3-A hydrophobic domains 4 and 6 and yeast Stt3p domains 2, 3a, 3c, and 6 we measured reduced insertion efficiency into the ER membrane. 28512128 7 78 theme hydrophobic 1125:1135 arg1 3a 1180:1181 3a 1180:1181 3a 1180:1181 However, for the mouse STT3-A hydrophobic domains 4 and 6 and yeast Stt3p domains 2, 3a, 3c, and 6 we measured reduced insertion efficiency into the ER membrane. 28512128 7 78 theme hydrophobic 1125:1135 arg1 domains 1137:1143 the mouse STT3-A hydrophobic domains 4 and 6 1108:1151 the mouse STT3-A hydrophobic domains 4 and 6 1108:1151 However, for the mouse STT3-A hydrophobic domains 4 and 6 and yeast Stt3p domains 2, 3a, 3c, and 6 we measured reduced insertion efficiency into the ER membrane. 28512128 3 79 from discrepancy 526:536 arg1 topology 556:563 the structural topology 541:563 the structural topology of the bacterial versus eukaryotic proteins 541:607 However, understanding the catalytic determinants of this system has been challenging, in part because of a discrepancy in the structural topology of the bacterial versus eukaryotic proteins and incomplete information about the mechanism of membrane integration. 28512128 7 80 theme yeast 1157:1161 arg1 domains 1169:1175 yeast Stt3p domains 1157:1175 yeast Stt3p domains 1157:1175 However, for the mouse STT3-A hydrophobic domains 4 and 6 and yeast Stt3p domains 2, 3a, 3c, and 6 we measured reduced insertion efficiency into the ER membrane. 26260331 1 0 theme infection 304:312 arg1 breakthrough 284:295 breakthrough 284:295 breakthrough of HBV infection in patients with anti-HBs antibodies 284:349 Immune escape mutants with mutations in the hepatitis B surface antigen (HBsAg) major hydrophilic region (MHR) often emerge in association with diagnostic failure or breakthrough of HBV infection in patients with anti-HBs antibodies. 26260331 1 0 theme infection 304:312 arg1 failure 273:279 diagnostic failure 262:279 diagnostic failure 262:279 Immune escape mutants with mutations in the hepatitis B surface antigen (HBsAg) major hydrophilic region (MHR) often emerge in association with diagnostic failure or breakthrough of HBV infection in patients with anti-HBs antibodies. 26260331 1 1 from breakthrough 284:295 arg1 patients 317:324 patients 317:324 patients with anti-HBs antibodies 317:349 Immune escape mutants with mutations in the hepatitis B surface antigen (HBsAg) major hydrophilic region (MHR) often emerge in association with diagnostic failure or breakthrough of HBV infection in patients with anti-HBs antibodies. 26260331 1 2 with patients 317:324 arg1 antibodies 340:349 anti-HBs antibodies 331:349 anti-HBs antibodies 331:349 Immune escape mutants with mutations in the hepatitis B surface antigen (HBsAg) major hydrophilic region (MHR) often emerge in association with diagnostic failure or breakthrough of HBV infection in patients with anti-HBs antibodies. 26260331 6 3 theme virion 965:970 arg1 secretion 972:980 virion secretion 965:980 virion secretion 965:980 The results demonstrated that sT123N substitution impaired virion secretion, resulting in intracellular retention of HBcAg. 26260331 7 4 theme HBsAg 1167:1171 arg1 clearance 1173:1181 HBsAg clearance 1167:1181 HBsAg clearance 1167:1181 Using the HBV HI mouse model, we found that mice mounted significantly stronger antibody responses to HBsAg and HBcAg, which accelerated HBsAg clearance. 26260331 1 5 from mutations 145:153 arg1 region 216:221 the hepatitis B surface antigen (HBsAg) major hydrophilic region 158:221 the hepatitis B surface antigen (HBsAg) major hydrophilic region (MHR) 158:227 Immune escape mutants with mutations in the hepatitis B surface antigen (HBsAg) major hydrophilic region (MHR) often emerge in association with diagnostic failure or breakthrough of HBV infection in patients with anti-HBs antibodies. 26260331 1 5 from mutations 145:153 arg1 MHR 224:226 MHR 224:226 MHR 224:226 Immune escape mutants with mutations in the hepatitis B surface antigen (HBsAg) major hydrophilic region (MHR) often emerge in association with diagnostic failure or breakthrough of HBV infection in patients with anti-HBs antibodies. 26260331 0 6 theme in 93:94 arg1 clearance 107:115 in vivo HBsAg clearance 93:115 in vivo HBsAg clearance 93:115 HBsAg sT123N mutation induces stronger antibody responses to HBsAg and HBcAg and accelerates in vivo HBsAg clearance. 26260331 1 7 from failure 273:279 arg1 patients 317:324 patients 317:324 patients with anti-HBs antibodies 317:349 Immune escape mutants with mutations in the hepatitis B surface antigen (HBsAg) major hydrophilic region (MHR) often emerge in association with diagnostic failure or breakthrough of HBV infection in patients with anti-HBs antibodies. 26260331 3 8 theme additional 530:539 arg1 forms 556:560 additional N-glycosylated forms 530:560 additional N-glycosylated forms of HBsAg 530:569 We have previously showed that sT123N substitution could generate additional N-glycosylated forms of HBsAg. 26260331 8 9 theme additional 1190:1199 arg1 N-glycosylation 1201:1215 additional N-glycosylation 1190:1215 additional N-glycosylation generated by amino acid substitutions in HBsAg MHR 1190:1266 Thus, additional N-glycosylation generated by amino acid substitutions in HBsAg MHR may significantly modulate specific host immune responses and influence HBV infection in vivo. 26260331 6 10 theme sT123N 936:941 arg1 substitution 943:954 sT123N substitution 936:954 sT123N substitution 936:954 The results demonstrated that sT123N substitution impaired virion secretion, resulting in intracellular retention of HBcAg. 26260331 4 11 theme hydrodynamic 775:786 arg1 injection 788:796 hydrodynamic injection 775:796 hydrodynamic injection (HI) 775:801 In the present study, 1.3-fold-overlength HBV genomes containing the sT123N substitution were digested from the pHBV1.3-sT123N construct and subcloned into the pAAV vector to generate pAAV1.3-sT123N for hydrodynamic injection (HI) in mice. 26260331 4 11 theme hydrodynamic 775:786 arg1 HI 799:800 HI 799:800 HI 799:800 In the present study, 1.3-fold-overlength HBV genomes containing the sT123N substitution were digested from the pHBV1.3-sT123N construct and subcloned into the pAAV vector to generate pAAV1.3-sT123N for hydrodynamic injection (HI) in mice. 26260331 2 12 contain have 413:416 arg2 site 458:461 an additional potential N-glycosylation site 418:461 an additional potential N-glycosylation site 418:461 Some mutants harboring substitutions to Asn in HBsAg MHR may have an additional potential N-glycosylation site. 26260331 2 12 contain have 413:416 arg1 mutants 357:363 Some mutants 352:363 Some mutants harboring substitutions to Asn in HBsAg MHR 352:407 Some mutants harboring substitutions to Asn in HBsAg MHR may have an additional potential N-glycosylation site. 26260331 3 13 theme N-glycosylated 541:554 arg1 forms 556:560 additional N-glycosylated forms 530:560 additional N-glycosylated forms of HBsAg 530:569 We have previously showed that sT123N substitution could generate additional N-glycosylated forms of HBsAg. 26260331 4 14 theme pAAV 732:735 arg1 vector 737:742 the pAAV vector 728:742 the pAAV vector 728:742 In the present study, 1.3-fold-overlength HBV genomes containing the sT123N substitution were digested from the pHBV1.3-sT123N construct and subcloned into the pAAV vector to generate pAAV1.3-sT123N for hydrodynamic injection (HI) in mice. 26260331 0 15 theme HBsAg 101:105 arg1 clearance 107:115 in vivo HBsAg clearance 93:115 in vivo HBsAg clearance 93:115 HBsAg sT123N mutation induces stronger antibody responses to HBsAg and HBcAg and accelerates in vivo HBsAg clearance. 26260331 1 16 theme anti-HBs 331:338 arg1 antibodies 340:349 anti-HBs antibodies 331:349 anti-HBs antibodies 331:349 Immune escape mutants with mutations in the hepatitis B surface antigen (HBsAg) major hydrophilic region (MHR) often emerge in association with diagnostic failure or breakthrough of HBV infection in patients with anti-HBs antibodies. 26260331 5 17 theme Viral 812:816 arg1 expression 818:827 Viral expression 812:827 Viral expression 812:827 Viral expression and replication were phenotypically characterized by transient transfection. 26260331 0 18 dep in 93:94 arg1 vivo 96:99 vivo 96:99 vivo 96:99 HBsAg sT123N mutation induces stronger antibody responses to HBsAg and HBcAg and accelerates in vivo HBsAg clearance. 26260331 8 19 theme immune 1309:1314 arg1 responses 1316:1324 specific host immune responses 1295:1324 specific host immune responses 1295:1324 Thus, additional N-glycosylation generated by amino acid substitutions in HBsAg MHR may significantly modulate specific host immune responses and influence HBV infection in vivo. 26260331 5 20 theme transient 882:890 arg1 transfection 892:903 transient transfection 882:903 transient transfection 882:903 Viral expression and replication were phenotypically characterized by transient transfection. 26260331 4 21 theme present 579:585 arg1 study 587:591 the present study 575:591 the present study 575:591 In the present study, 1.3-fold-overlength HBV genomes containing the sT123N substitution were digested from the pHBV1.3-sT123N construct and subcloned into the pAAV vector to generate pAAV1.3-sT123N for hydrodynamic injection (HI) in mice. 26260331 9 22 link N-linked 1448:1455 arg1 glycosylation 1457:1469 N-linked glycosylation 1448:1469 N-linked glycosylation 1448:1469 Our results help further the understanding of the role of immune escape mutants with N-linked glycosylation in the biology of HBV infection. 26260331 8 23 theme amino 1230:1234 arg1 substitutions 1241:1253 amino acid substitutions 1230:1253 amino acid substitutions in HBsAg MHR 1230:1266 Thus, additional N-glycosylation generated by amino acid substitutions in HBsAg MHR may significantly modulate specific host immune responses and influence HBV infection in vivo. 26260331 1 24 theme hepatitis 162:170 arg1 HBsAg 191:195 HBsAg 191:195 HBsAg 191:195 Immune escape mutants with mutations in the hepatitis B surface antigen (HBsAg) major hydrophilic region (MHR) often emerge in association with diagnostic failure or breakthrough of HBV infection in patients with anti-HBs antibodies. 26260331 1 24 theme hepatitis 162:170 arg1 antigen 182:188 the hepatitis B surface antigen 158:188 the hepatitis B surface antigen (HBsAg) major hydrophilic region (MHR) 158:227 Immune escape mutants with mutations in the hepatitis B surface antigen (HBsAg) major hydrophilic region (MHR) often emerge in association with diagnostic failure or breakthrough of HBV infection in patients with anti-HBs antibodies. 26260331 0 25 theme sT123N 6:11 arg1 mutation 13:20 HBsAg sT123N mutation 0:20 HBsAg sT123N mutation 0:20 HBsAg sT123N mutation induces stronger antibody responses to HBsAg and HBcAg and accelerates in vivo HBsAg clearance. 26260331 4 26 from pAAV1.3-sT123N 756:769 arg1 mice 806:809 mice 806:809 mice 806:809 In the present study, 1.3-fold-overlength HBV genomes containing the sT123N substitution were digested from the pHBV1.3-sT123N construct and subcloned into the pAAV vector to generate pAAV1.3-sT123N for hydrodynamic injection (HI) in mice. 26260331 3 27 theme HBsAg 565:569 arg1 forms 556:560 additional N-glycosylated forms 530:560 additional N-glycosylated forms of HBsAg 530:569 We have previously showed that sT123N substitution could generate additional N-glycosylated forms of HBsAg. 26260331 1 28 theme B 172:172 arg1 HBsAg 191:195 HBsAg 191:195 HBsAg 191:195 Immune escape mutants with mutations in the hepatitis B surface antigen (HBsAg) major hydrophilic region (MHR) often emerge in association with diagnostic failure or breakthrough of HBV infection in patients with anti-HBs antibodies. 26260331 1 28 theme B 172:172 arg1 antigen 182:188 the hepatitis B surface antigen 158:188 the hepatitis B surface antigen (HBsAg) major hydrophilic region (MHR) 158:227 Immune escape mutants with mutations in the hepatitis B surface antigen (HBsAg) major hydrophilic region (MHR) often emerge in association with diagnostic failure or breakthrough of HBV infection in patients with anti-HBs antibodies. 26260331 0 29 theme HBsAg 0:4 arg1 mutation 13:20 HBsAg sT123N mutation 0:20 HBsAg sT123N mutation 0:20 HBsAg sT123N mutation induces stronger antibody responses to HBsAg and HBcAg and accelerates in vivo HBsAg clearance. 26260331 8 30 theme specific 1295:1302 arg1 responses 1316:1324 specific host immune responses 1295:1324 specific host immune responses 1295:1324 Thus, additional N-glycosylation generated by amino acid substitutions in HBsAg MHR may significantly modulate specific host immune responses and influence HBV infection in vivo. 26260331 1 31 theme surface 174:180 arg1 HBsAg 191:195 HBsAg 191:195 HBsAg 191:195 Immune escape mutants with mutations in the hepatitis B surface antigen (HBsAg) major hydrophilic region (MHR) often emerge in association with diagnostic failure or breakthrough of HBV infection in patients with anti-HBs antibodies. 26260331 1 31 theme surface 174:180 arg1 antigen 182:188 the hepatitis B surface antigen 158:188 the hepatitis B surface antigen (HBsAg) major hydrophilic region (MHR) 158:227 Immune escape mutants with mutations in the hepatitis B surface antigen (HBsAg) major hydrophilic region (MHR) often emerge in association with diagnostic failure or breakthrough of HBV infection in patients with anti-HBs antibodies. 26260331 6 32 theme HBcAg 1023:1027 arg1 retention 1010:1018 intracellular retention 996:1018 intracellular retention of HBcAg 996:1027 The results demonstrated that sT123N substitution impaired virion secretion, resulting in intracellular retention of HBcAg. 26260331 7 33 theme antibody 1110:1117 arg1 responses 1119:1127 significantly stronger antibody responses 1087:1127 significantly stronger antibody responses to HBsAg and HBcAg 1087:1146 Using the HBV HI mouse model, we found that mice mounted significantly stronger antibody responses to HBsAg and HBcAg, which accelerated HBsAg clearance. 26260331 1 34 with association 245:255 arg1 breakthrough 284:295 breakthrough 284:295 breakthrough of HBV infection in patients with anti-HBs antibodies 284:349 Immune escape mutants with mutations in the hepatitis B surface antigen (HBsAg) major hydrophilic region (MHR) often emerge in association with diagnostic failure or breakthrough of HBV infection in patients with anti-HBs antibodies. 26260331 1 34 with association 245:255 arg1 failure 273:279 diagnostic failure 262:279 diagnostic failure 262:279 Immune escape mutants with mutations in the hepatitis B surface antigen (HBsAg) major hydrophilic region (MHR) often emerge in association with diagnostic failure or breakthrough of HBV infection in patients with anti-HBs antibodies. 26260331 9 35 theme escape 1428:1433 arg1 mutants 1435:1441 immune escape mutants 1421:1441 immune escape mutants with N-linked glycosylation 1421:1469 Our results help further the understanding of the role of immune escape mutants with N-linked glycosylation in the biology of HBV infection. 26260331 1 36 theme antigen 182:188 arg1 region 216:221 the hepatitis B surface antigen (HBsAg) major hydrophilic region 158:221 the hepatitis B surface antigen (HBsAg) major hydrophilic region (MHR) 158:227 Immune escape mutants with mutations in the hepatitis B surface antigen (HBsAg) major hydrophilic region (MHR) often emerge in association with diagnostic failure or breakthrough of HBV infection in patients with anti-HBs antibodies. 26260331 1 36 theme antigen 182:188 arg1 MHR 224:226 MHR 224:226 MHR 224:226 Immune escape mutants with mutations in the hepatitis B surface antigen (HBsAg) major hydrophilic region (MHR) often emerge in association with diagnostic failure or breakthrough of HBV infection in patients with anti-HBs antibodies. 26260331 7 37 theme HI 1044:1045 arg1 model 1053:1057 the HBV HI mouse model 1036:1057 the HBV HI mouse model 1036:1057 Using the HBV HI mouse model, we found that mice mounted significantly stronger antibody responses to HBsAg and HBcAg, which accelerated HBsAg clearance. 26260331 4 38 theme 1.3-fold-overlength 594:612 arg1 genomes 618:624 1.3-fold-overlength HBV genomes 594:624 1.3-fold-overlength HBV genomes containing the sT123N substitution 594:659 In the present study, 1.3-fold-overlength HBV genomes containing the sT123N substitution were digested from the pHBV1.3-sT123N construct and subcloned into the pAAV vector to generate pAAV1.3-sT123N for hydrodynamic injection (HI) in mice. 26260331 8 39 from substitutions 1241:1253 arg1 MHR 1264:1266 HBsAg MHR 1258:1266 HBsAg MHR 1258:1266 Thus, additional N-glycosylation generated by amino acid substitutions in HBsAg MHR may significantly modulate specific host immune responses and influence HBV infection in vivo. 26260331 3 40 theme sT123N 495:500 arg1 substitution 502:513 sT123N substitution 495:513 sT123N substitution 495:513 We have previously showed that sT123N substitution could generate additional N-glycosylated forms of HBsAg. 26260331 0 41 theme antibody 39:46 arg1 responses 48:56 stronger antibody responses 30:56 stronger antibody responses to HBsAg and HBcAg 30:75 HBsAg sT123N mutation induces stronger antibody responses to HBsAg and HBcAg and accelerates in vivo HBsAg clearance. 26260331 1 42 theme diagnostic 262:271 arg1 failure 273:279 diagnostic failure 262:279 diagnostic failure 262:279 Immune escape mutants with mutations in the hepatitis B surface antigen (HBsAg) major hydrophilic region (MHR) often emerge in association with diagnostic failure or breakthrough of HBV infection in patients with anti-HBs antibodies. 26260331 2 43 gly N-glycosylation 442:456 arg2 site 458:461 an additional potential N-glycosylation site 418:461 an additional potential N-glycosylation site 418:461 Some mutants harboring substitutions to Asn in HBsAg MHR may have an additional potential N-glycosylation site. 26260331 8 44 theme host 1304:1307 arg1 responses 1316:1324 specific host immune responses 1295:1324 specific host immune responses 1295:1324 Thus, additional N-glycosylation generated by amino acid substitutions in HBsAg MHR may significantly modulate specific host immune responses and influence HBV infection in vivo. 26260331 8 45 theme HBV 1340:1342 arg1 infection 1344:1352 HBV infection 1340:1352 HBV infection 1340:1352 Thus, additional N-glycosylation generated by amino acid substitutions in HBsAg MHR may significantly modulate specific host immune responses and influence HBV infection in vivo. 26260331 0 46 theme stronger 30:37 arg1 responses 48:56 stronger antibody responses 30:56 stronger antibody responses to HBsAg and HBcAg 30:75 HBsAg sT123N mutation induces stronger antibody responses to HBsAg and HBcAg and accelerates in vivo HBsAg clearance. 26260331 6 47 theme intracellular 996:1008 arg1 retention 1010:1018 intracellular retention 996:1018 intracellular retention of HBcAg 996:1027 The results demonstrated that sT123N substitution impaired virion secretion, resulting in intracellular retention of HBcAg. 26260331 2 48 theme N-glycosylation 442:456 arg1 site 458:461 an additional potential N-glycosylation site 418:461 an additional potential N-glycosylation site 418:461 Some mutants harboring substitutions to Asn in HBsAg MHR may have an additional potential N-glycosylation site. 26260331 4 49 contain containing 626:635 arg2 substitution 648:659 the sT123N substitution 637:659 the sT123N substitution 637:659 In the present study, 1.3-fold-overlength HBV genomes containing the sT123N substitution were digested from the pHBV1.3-sT123N construct and subcloned into the pAAV vector to generate pAAV1.3-sT123N for hydrodynamic injection (HI) in mice. 26260331 4 49 contain containing 626:635 arg1 genomes 618:624 1.3-fold-overlength HBV genomes 594:624 1.3-fold-overlength HBV genomes containing the sT123N substitution 594:659 In the present study, 1.3-fold-overlength HBV genomes containing the sT123N substitution were digested from the pHBV1.3-sT123N construct and subcloned into the pAAV vector to generate pAAV1.3-sT123N for hydrodynamic injection (HI) in mice. 26260331 9 50 from understanding 1392:1404 arg1 biology 1478:1484 the biology 1474:1484 the biology of HBV infection 1474:1501 Our results help further the understanding of the role of immune escape mutants with N-linked glycosylation in the biology of HBV infection. 26260331 4 51 theme sT123N 641:646 arg1 substitution 648:659 the sT123N substitution 637:659 the sT123N substitution 637:659 In the present study, 1.3-fold-overlength HBV genomes containing the sT123N substitution were digested from the pHBV1.3-sT123N construct and subcloned into the pAAV vector to generate pAAV1.3-sT123N for hydrodynamic injection (HI) in mice. 26260331 2 52 theme potential 432:440 arg1 site 458:461 an additional potential N-glycosylation site 418:461 an additional potential N-glycosylation site 418:461 Some mutants harboring substitutions to Asn in HBsAg MHR may have an additional potential N-glycosylation site. 26260331 9 53 theme role 1413:1416 arg1 understanding 1392:1404 the understanding 1388:1404 the understanding of the role of immune escape mutants with N-linked glycosylation in the biology of HBV infection 1388:1501 Our results help further the understanding of the role of immune escape mutants with N-linked glycosylation in the biology of HBV infection. 26260331 8 54 theme HBsAg 1258:1262 arg1 MHR 1264:1266 HBsAg MHR 1258:1266 HBsAg MHR 1258:1266 Thus, additional N-glycosylation generated by amino acid substitutions in HBsAg MHR may significantly modulate specific host immune responses and influence HBV infection in vivo. 26260331 9 55 gly glycosylation 1457:1469 arg1 mutants 1435:1441 immune escape mutants 1421:1441 immune escape mutants with N-linked glycosylation 1421:1469 Our results help further the understanding of the role of immune escape mutants with N-linked glycosylation in the biology of HBV infection. 26260331 9 56 theme HBV 1489:1491 arg1 infection 1493:1501 HBV infection 1489:1501 HBV infection 1489:1501 Our results help further the understanding of the role of immune escape mutants with N-linked glycosylation in the biology of HBV infection. 26260331 7 57 theme stronger 1101:1108 arg1 responses 1119:1127 significantly stronger antibody responses 1087:1127 significantly stronger antibody responses to HBsAg and HBcAg 1087:1146 Using the HBV HI mouse model, we found that mice mounted significantly stronger antibody responses to HBsAg and HBcAg, which accelerated HBsAg clearance. 26260331 2 58 theme additional 421:430 arg1 site 458:461 an additional potential N-glycosylation site 418:461 an additional potential N-glycosylation site 418:461 Some mutants harboring substitutions to Asn in HBsAg MHR may have an additional potential N-glycosylation site. 26260331 9 59 theme immune 1421:1426 arg1 mutants 1435:1441 immune escape mutants 1421:1441 immune escape mutants with N-linked glycosylation 1421:1469 Our results help further the understanding of the role of immune escape mutants with N-linked glycosylation in the biology of HBV infection. 26260331 9 60 from biology 1478:1484 arg1 understanding 1392:1404 the understanding 1388:1404 the understanding of the role of immune escape mutants with N-linked glycosylation in the biology of HBV infection 1388:1501 Our results help further the understanding of the role of immune escape mutants with N-linked glycosylation in the biology of HBV infection. 26260331 7 61 theme mouse 1047:1051 arg1 model 1053:1057 the HBV HI mouse model 1036:1057 the HBV HI mouse model 1036:1057 Using the HBV HI mouse model, we found that mice mounted significantly stronger antibody responses to HBsAg and HBcAg, which accelerated HBsAg clearance. 26260331 1 62 with mutants 132:138 arg1 mutations 145:153 mutations 145:153 mutations in the hepatitis B surface antigen (HBsAg) major hydrophilic region (MHR) 145:227 Immune escape mutants with mutations in the hepatitis B surface antigen (HBsAg) major hydrophilic region (MHR) often emerge in association with diagnostic failure or breakthrough of HBV infection in patients with anti-HBs antibodies. 26260331 8 63 theme acid 1236:1239 arg1 substitutions 1241:1253 amino acid substitutions 1230:1253 amino acid substitutions in HBsAg MHR 1230:1266 Thus, additional N-glycosylation generated by amino acid substitutions in HBsAg MHR may significantly modulate specific host immune responses and influence HBV infection in vivo. 26260331 1 64 theme Immune 118:123 arg1 mutants 132:138 Immune escape mutants 118:138 Immune escape mutants with mutations in the hepatitis B surface antigen (HBsAg) major hydrophilic region (MHR) 118:227 Immune escape mutants with mutations in the hepatitis B surface antigen (HBsAg) major hydrophilic region (MHR) often emerge in association with diagnostic failure or breakthrough of HBV infection in patients with anti-HBs antibodies. 26260331 9 65 theme mutants 1435:1441 arg1 role 1413:1416 the role 1409:1416 the role of immune escape mutants with N-linked glycosylation in the biology of HBV infection 1409:1501 Our results help further the understanding of the role of immune escape mutants with N-linked glycosylation in the biology of HBV infection. 26260331 1 66 theme major 198:202 arg1 region 216:221 the hepatitis B surface antigen (HBsAg) major hydrophilic region 158:221 the hepatitis B surface antigen (HBsAg) major hydrophilic region (MHR) 158:227 Immune escape mutants with mutations in the hepatitis B surface antigen (HBsAg) major hydrophilic region (MHR) often emerge in association with diagnostic failure or breakthrough of HBV infection in patients with anti-HBs antibodies. 26260331 1 66 theme major 198:202 arg1 MHR 224:226 MHR 224:226 MHR 224:226 Immune escape mutants with mutations in the hepatitis B surface antigen (HBsAg) major hydrophilic region (MHR) often emerge in association with diagnostic failure or breakthrough of HBV infection in patients with anti-HBs antibodies. 26260331 7 67 theme HBV 1040:1042 arg1 model 1053:1057 the HBV HI mouse model 1036:1057 the HBV HI mouse model 1036:1057 Using the HBV HI mouse model, we found that mice mounted significantly stronger antibody responses to HBsAg and HBcAg, which accelerated HBsAg clearance. 26260331 1 68 theme escape 125:130 arg1 mutants 132:138 Immune escape mutants 118:138 Immune escape mutants with mutations in the hepatitis B surface antigen (HBsAg) major hydrophilic region (MHR) 118:227 Immune escape mutants with mutations in the hepatitis B surface antigen (HBsAg) major hydrophilic region (MHR) often emerge in association with diagnostic failure or breakthrough of HBV infection in patients with anti-HBs antibodies. 26260331 7 69 dep mounted 1079:1085 arg1 accelerated 1155:1165 accelerated 1155:1165 accelerated HBsAg clearance 1155:1181 Using the HBV HI mouse model, we found that mice mounted significantly stronger antibody responses to HBsAg and HBcAg, which accelerated HBsAg clearance. 26260331 1 70 theme hydrophilic 204:214 arg1 region 216:221 the hepatitis B surface antigen (HBsAg) major hydrophilic region 158:221 the hepatitis B surface antigen (HBsAg) major hydrophilic region (MHR) 158:227 Immune escape mutants with mutations in the hepatitis B surface antigen (HBsAg) major hydrophilic region (MHR) often emerge in association with diagnostic failure or breakthrough of HBV infection in patients with anti-HBs antibodies. 26260331 1 70 theme hydrophilic 204:214 arg1 MHR 224:226 MHR 224:226 MHR 224:226 Immune escape mutants with mutations in the hepatitis B surface antigen (HBsAg) major hydrophilic region (MHR) often emerge in association with diagnostic failure or breakthrough of HBV infection in patients with anti-HBs antibodies. 26260331 9 71 from role 1413:1416 arg1 biology 1478:1484 the biology 1474:1484 the biology of HBV infection 1474:1501 Our results help further the understanding of the role of immune escape mutants with N-linked glycosylation in the biology of HBV infection. 26260331 2 72 theme HBsAg 399:403 arg1 MHR 405:407 HBsAg MHR 399:407 HBsAg MHR 399:407 Some mutants harboring substitutions to Asn in HBsAg MHR may have an additional potential N-glycosylation site. 26260331 3 73 gly N-glycosylated 541:554 arg1 HBsAg 565:569 HBsAg 565:569 HBsAg 565:569 We have previously showed that sT123N substitution could generate additional N-glycosylated forms of HBsAg. 26260331 3 73 gly N-glycosylated 541:554 arg1 forms 556:560 additional N-glycosylated forms 530:560 additional N-glycosylated forms of HBsAg 530:569 We have previously showed that sT123N substitution could generate additional N-glycosylated forms of HBsAg. 26260331 9 74 theme infection 1493:1501 arg1 biology 1478:1484 the biology 1474:1484 the biology of HBV infection 1474:1501 Our results help further the understanding of the role of immune escape mutants with N-linked glycosylation in the biology of HBV infection. 26260331 9 75 theme N-linked 1448:1455 arg1 glycosylation 1457:1469 N-linked glycosylation 1448:1469 N-linked glycosylation 1448:1469 Our results help further the understanding of the role of immune escape mutants with N-linked glycosylation in the biology of HBV infection. 26260331 1 76 theme HBV 300:302 arg1 infection 304:312 HBV infection 300:312 HBV infection 300:312 Immune escape mutants with mutations in the hepatitis B surface antigen (HBsAg) major hydrophilic region (MHR) often emerge in association with diagnostic failure or breakthrough of HBV infection in patients with anti-HBs antibodies. 26260331 9 77 with mutants 1435:1441 arg1 glycosylation 1457:1469 N-linked glycosylation 1448:1469 N-linked glycosylation 1448:1469 Our results help further the understanding of the role of immune escape mutants with N-linked glycosylation in the biology of HBV infection. 26260331 4 78 theme pHBV1.3-sT123N 684:697 arg1 construct 699:707 the pHBV1.3-sT123N construct 680:707 the pHBV1.3-sT123N construct 680:707 In the present study, 1.3-fold-overlength HBV genomes containing the sT123N substitution were digested from the pHBV1.3-sT123N construct and subcloned into the pAAV vector to generate pAAV1.3-sT123N for hydrodynamic injection (HI) in mice. 26260331 4 79 theme HBV 614:616 arg1 genomes 618:624 1.3-fold-overlength HBV genomes 594:624 1.3-fold-overlength HBV genomes containing the sT123N substitution 594:659 In the present study, 1.3-fold-overlength HBV genomes containing the sT123N substitution were digested from the pHBV1.3-sT123N construct and subcloned into the pAAV vector to generate pAAV1.3-sT123N for hydrodynamic injection (HI) in mice. 26867212 5 0 gly glycoproteins 819:831 arg1 glycoproteins 819:831 glycoproteins 819:831 glycoproteins 819:831 Paramyxoviral cell entry requires the coordinated actions of two viral membrane glycoproteins: the attachment (HN/H/G) and fusion (F) glycoproteins. 26867212 7 1 theme cell-cell 1081:1089 arg1 fusion 1091:1096 altered cell-cell fusion 1073:1096 altered cell-cell fusion 1073:1096 We mutated the identified HeV G O-glycosylation sites and found mutants with altered cell-cell fusion, G conformation, G/F association, viral entry in a pseudotyped viral system, and, quite unexpectedly, pseudotyped viral F protein incorporation and processing phenotypes. 26867212 9 2 theme equivalent 1371:1380 arg1 mutants 1386:1392 equivalent NiV mutants 1371:1392 equivalent NiV mutants 1371:1392 These phenotypes were broadly conserved for equivalent NiV mutants. 26867212 5 3 dep attachment 784:793 arg1 glycoproteins 819:831 glycoproteins 819:831 glycoproteins 819:831 Paramyxoviral cell entry requires the coordinated actions of two viral membrane glycoproteins: the attachment (HN/H/G) and fusion (F) glycoproteins. 26867212 6 4 from sites 843:847 arg1 G 856:856 HeV G 852:856 HeV G 852:856 O-glycan sites in HeV G were recently identified, facilitating use of the attachment protein of this deadly paramyxovirus as a model to study O-glycan functions. 26867212 6 5 theme HeV 852:854 arg1 G 856:856 HeV G 852:856 HeV G 852:856 O-glycan sites in HeV G were recently identified, facilitating use of the attachment protein of this deadly paramyxovirus as a model to study O-glycan functions. 26867212 10 6 theme O-glycan 1527:1534 arg1 functions 1536:1544 O-glycan functions 1527:1544 O-glycan functions in other paramyxoviruses and enveloped viruses 1527:1591 Thus our results identify multiple novel and pathologically important functions of paramyxoviral O-glycans, paving the way to study O-glycan functions in other paramyxoviruses and enveloped viruses. 26867212 2 7 theme many 276:279 arg1 pathogens 281:289 many pathogens 276:289 many pathogens 276:289 Both microbial and host protein glycans are used by many pathogens for host invasion and immune evasion, yet little is known about the roles of O-glycans in viral pathogenesis. 26867212 10 8 theme enveloped 1575:1583 arg1 viruses 1585:1591 enveloped viruses 1575:1591 enveloped viruses 1575:1591 Thus our results identify multiple novel and pathologically important functions of paramyxoviral O-glycans, paving the way to study O-glycan functions in other paramyxoviruses and enveloped viruses. 26867212 2 9 theme immune 313:318 arg1 evasion 320:326 immune evasion 313:326 immune evasion 313:326 Both microbial and host protein glycans are used by many pathogens for host invasion and immune evasion, yet little is known about the roles of O-glycans in viral pathogenesis. 26867212 4 10 theme deadly 626:631 arg1 NiV 654:656 the deadly Henipaviruses Nipah (NiV) and Hendra (HeV) viruses 622:682 NiV 654:656 The paramyxovirus family includes many important pathogens, such as measles, mumps, parainfluenza, metapneumo- and the deadly Henipaviruses Nipah (NiV) and Hendra (HeV) viruses. 26867212 7 11 theme G 1026:1026 arg1 sites 1044:1048 the identified HeV G O-glycosylation sites 1007:1048 the identified HeV G O-glycosylation sites 1007:1048 We mutated the identified HeV G O-glycosylation sites and found mutants with altered cell-cell fusion, G conformation, G/F association, viral entry in a pseudotyped viral system, and, quite unexpectedly, pseudotyped viral F protein incorporation and processing phenotypes. 26867212 6 12 theme attachment 908:917 arg1 protein 919:925 the attachment protein 904:925 the attachment protein 904:925 O-glycan sites in HeV G were recently identified, facilitating use of the attachment protein of this deadly paramyxovirus as a model to study O-glycan functions. 26867212 7 13 from entry 1138:1142 arg1 system 1167:1172 a pseudotyped viral system 1147:1172 a pseudotyped viral system 1147:1172 We mutated the identified HeV G O-glycosylation sites and found mutants with altered cell-cell fusion, G conformation, G/F association, viral entry in a pseudotyped viral system, and, quite unexpectedly, pseudotyped viral F protein incorporation and processing phenotypes. 26867212 4 14 theme Nipah 647:651 arg1 NiV 654:656 the deadly Henipaviruses Nipah (NiV) and Hendra (HeV) viruses 622:682 NiV 654:656 The paramyxovirus family includes many important pathogens, such as measles, mumps, parainfluenza, metapneumo- and the deadly Henipaviruses Nipah (NiV) and Hendra (HeV) viruses. 26867212 5 15 theme cell 699:702 arg1 entry 704:708 Paramyxoviral cell entry 685:708 Paramyxoviral cell entry 685:708 Paramyxoviral cell entry requires the coordinated actions of two viral membrane glycoproteins: the attachment (HN/H/G) and fusion (F) glycoproteins. 26867212 1 16 theme O-linked 120:127 arg1 glycosylation 129:141 O-linked glycosylation 120:141 O-linked glycosylation 120:141 O-linked glycosylation is a ubiquitous protein modification in organisms belonging to several kingdoms. 26867212 1 16 theme O-linked 120:127 arg1 modification 167:178 a ubiquitous protein modification 146:178 a ubiquitous protein modification in organisms belonging to several kingdoms 146:221 O-linked glycosylation is a ubiquitous protein modification in organisms belonging to several kingdoms. 26867212 0 17 theme First 55:59 arg1 Functions 70:78 The First O-glycan Functions 51:78 Multiple Novel Functions of Henipavirus O-glycans: The First O-glycan Functions Identified in the Paramyxovirus Family. 0:118 Multiple Novel Functions of Henipavirus O-glycans: The First O-glycan Functions Identified in the Paramyxovirus Family. 26867212 1 18 theme ubiquitous 148:157 arg1 glycosylation 129:141 O-linked glycosylation 120:141 O-linked glycosylation 120:141 O-linked glycosylation is a ubiquitous protein modification in organisms belonging to several kingdoms. 26867212 1 18 theme ubiquitous 148:157 arg1 modification 167:178 a ubiquitous protein modification 146:178 a ubiquitous protein modification in organisms belonging to several kingdoms 146:221 O-linked glycosylation is a ubiquitous protein modification in organisms belonging to several kingdoms. 26867212 5 19 theme viral 750:754 arg1 glycoproteins 765:777 two viral membrane glycoproteins 746:777 two viral membrane glycoproteins: the attachment (HN/H/G) and fusion (F) glycoproteins 746:831 Paramyxoviral cell entry requires the coordinated actions of two viral membrane glycoproteins: the attachment (HN/H/G) and fusion (F) glycoproteins. 26867212 5 19 theme viral 750:754 arg1 attachment 784:793 the attachment 780:793 the attachment (HN/H/G) 780:802 Paramyxoviral cell entry requires the coordinated actions of two viral membrane glycoproteins: the attachment (HN/H/G) and fusion (F) glycoproteins. 26867212 5 19 theme viral 750:754 arg1 fusion 808:813 fusion 808:813 fusion (F) 808:817 Paramyxoviral cell entry requires the coordinated actions of two viral membrane glycoproteins: the attachment (HN/H/G) and fusion (F) glycoproteins. 26867212 7 20 from conformation 1101:1112 arg1 system 1167:1172 a pseudotyped viral system 1147:1172 a pseudotyped viral system 1147:1172 We mutated the identified HeV G O-glycosylation sites and found mutants with altered cell-cell fusion, G conformation, G/F association, viral entry in a pseudotyped viral system, and, quite unexpectedly, pseudotyped viral F protein incorporation and processing phenotypes. 26867212 8 21 theme important 1283:1291 arg1 functions 1293:1301 all important functions 1279:1301 all important functions of viral glycoproteins 1279:1324 These are all important functions of viral glycoproteins. 26867212 8 21 theme important 1283:1291 arg1 These 1269:1273 These 1269:1273 These 1269:1273 These are all important functions of viral glycoproteins. 26867212 6 22 theme deadly 935:940 arg1 paramyxovirus 942:954 this deadly paramyxovirus 930:954 this deadly paramyxovirus 930:954 O-glycan sites in HeV G were recently identified, facilitating use of the attachment protein of this deadly paramyxovirus as a model to study O-glycan functions. 26867212 2 23 theme viral 381:385 arg1 pathogenesis 387:398 viral pathogenesis 381:398 viral pathogenesis 381:398 Both microbial and host protein glycans are used by many pathogens for host invasion and immune evasion, yet little is known about the roles of O-glycans in viral pathogenesis. 26867212 5 24 theme coordinated 723:733 arg1 actions 735:741 the coordinated actions 719:741 the coordinated actions of two viral membrane glycoproteins: the attachment (HN/H/G) and fusion (F) glycoproteins 719:831 Paramyxoviral cell entry requires the coordinated actions of two viral membrane glycoproteins: the attachment (HN/H/G) and fusion (F) glycoproteins. 26867212 5 25 theme membrane 756:763 arg1 glycoproteins 765:777 two viral membrane glycoproteins 746:777 two viral membrane glycoproteins: the attachment (HN/H/G) and fusion (F) glycoproteins 746:831 Paramyxoviral cell entry requires the coordinated actions of two viral membrane glycoproteins: the attachment (HN/H/G) and fusion (F) glycoproteins. 26867212 5 25 theme membrane 756:763 arg1 attachment 784:793 the attachment 780:793 the attachment (HN/H/G) 780:802 Paramyxoviral cell entry requires the coordinated actions of two viral membrane glycoproteins: the attachment (HN/H/G) and fusion (F) glycoproteins. 26867212 5 25 theme membrane 756:763 arg1 fusion 808:813 fusion 808:813 fusion (F) 808:817 Paramyxoviral cell entry requires the coordinated actions of two viral membrane glycoproteins: the attachment (HN/H/G) and fusion (F) glycoproteins. 26867212 10 26 theme multiple 1421:1428 arg1 functions 1465:1473 multiple novel and pathologically important functions 1421:1473 multiple novel and pathologically important functions of paramyxoviral O-glycans 1421:1500 Thus our results identify multiple novel and pathologically important functions of paramyxoviral O-glycans, paving the way to study O-glycan functions in other paramyxoviruses and enveloped viruses. 26867212 8 27 theme glycoproteins 1312:1324 arg1 functions 1293:1301 all important functions 1279:1301 all important functions of viral glycoproteins 1279:1324 These are all important functions of viral glycoproteins. 26867212 8 27 theme glycoproteins 1312:1324 arg1 These 1269:1273 These 1269:1273 These 1269:1273 These are all important functions of viral glycoproteins. 26867212 2 28 theme O-glycans 368:376 arg1 roles 359:363 the roles 355:363 the roles of O-glycans in viral pathogenesis 355:398 Both microbial and host protein glycans are used by many pathogens for host invasion and immune evasion, yet little is known about the roles of O-glycans in viral pathogenesis. 26867212 0 29 theme Multiple 0:7 arg1 Functions 15:23 Multiple Novel Functions 0:23 Multiple Novel Functions of Henipavirus O-glycans: The First O-glycan Functions Identified in the Paramyxovirus Family. 0:118 Multiple Novel Functions of Henipavirus O-glycans: The First O-glycan Functions Identified in the Paramyxovirus Family. 26867212 7 30 theme G/F 1115:1117 arg1 association 1119:1129 G/F association 1115:1129 G/F association 1115:1129 We mutated the identified HeV G O-glycosylation sites and found mutants with altered cell-cell fusion, G conformation, G/F association, viral entry in a pseudotyped viral system, and, quite unexpectedly, pseudotyped viral F protein incorporation and processing phenotypes. 26867212 6 31 theme O-glycan 834:841 arg1 sites 843:847 O-glycan sites 834:847 O-glycan sites in HeV G 834:856 O-glycan sites in HeV G were recently identified, facilitating use of the attachment protein of this deadly paramyxovirus as a model to study O-glycan functions. 26867212 7 32 theme processing 1246:1255 arg1 phenotypes 1257:1266 processing phenotypes 1246:1266 processing phenotypes 1246:1266 We mutated the identified HeV G O-glycosylation sites and found mutants with altered cell-cell fusion, G conformation, G/F association, viral entry in a pseudotyped viral system, and, quite unexpectedly, pseudotyped viral F protein incorporation and processing phenotypes. 26867212 10 33 theme important 1455:1463 arg1 functions 1465:1473 multiple novel and pathologically important functions 1421:1473 multiple novel and pathologically important functions of paramyxoviral O-glycans 1421:1500 Thus our results identify multiple novel and pathologically important functions of paramyxoviral O-glycans, paving the way to study O-glycan functions in other paramyxoviruses and enveloped viruses. 26867212 0 34 theme Henipavirus 28:38 arg1 O-glycans 40:48 Henipavirus O-glycans 28:48 Henipavirus O-glycans 28:48 Multiple Novel Functions of Henipavirus O-glycans: The First O-glycan Functions Identified in the Paramyxovirus Family. 26867212 5 35 theme glycoproteins 765:777 arg1 actions 735:741 the coordinated actions 719:741 the coordinated actions of two viral membrane glycoproteins: the attachment (HN/H/G) and fusion (F) glycoproteins 719:831 Paramyxoviral cell entry requires the coordinated actions of two viral membrane glycoproteins: the attachment (HN/H/G) and fusion (F) glycoproteins. 26867212 3 36 theme significant 473:483 arg1 family 499:504 the significant paramyxovirus family 469:504 the significant paramyxovirus family 469:504 Reportedly, there is no single function attributed to O-glycans for the significant paramyxovirus family. 26867212 10 37 from functions 1536:1544 arg1 paramyxoviruses 1555:1569 other paramyxoviruses 1549:1569 other paramyxoviruses 1549:1569 Thus our results identify multiple novel and pathologically important functions of paramyxoviral O-glycans, paving the way to study O-glycan functions in other paramyxoviruses and enveloped viruses. 26867212 10 37 from functions 1536:1544 arg1 viruses 1585:1591 enveloped viruses 1575:1591 enveloped viruses 1575:1591 Thus our results identify multiple novel and pathologically important functions of paramyxoviral O-glycans, paving the way to study O-glycan functions in other paramyxoviruses and enveloped viruses. 26867212 7 38 theme F 1218:1218 arg1 incorporation 1228:1240 pseudotyped viral F protein incorporation 1200:1240 pseudotyped viral F protein incorporation 1200:1240 We mutated the identified HeV G O-glycosylation sites and found mutants with altered cell-cell fusion, G conformation, G/F association, viral entry in a pseudotyped viral system, and, quite unexpectedly, pseudotyped viral F protein incorporation and processing phenotypes. 26867212 4 39 theme many 541:544 arg1 mumps 584:588 mumps 584:588 mumps 584:588 The paramyxovirus family includes many important pathogens, such as measles, mumps, parainfluenza, metapneumo- and the deadly Henipaviruses Nipah (NiV) and Hendra (HeV) viruses. 26867212 4 39 theme many 541:544 arg1 pathogens 556:564 many important pathogens 541:564 many important pathogens 541:564 The paramyxovirus family includes many important pathogens, such as measles, mumps, parainfluenza, metapneumo- and the deadly Henipaviruses Nipah (NiV) and Hendra (HeV) viruses. 26867212 4 39 theme many 541:544 arg1 parainfluenza 591:603 parainfluenza 591:603 parainfluenza 591:603 The paramyxovirus family includes many important pathogens, such as measles, mumps, parainfluenza, metapneumo- and the deadly Henipaviruses Nipah (NiV) and Hendra (HeV) viruses. 26867212 4 39 theme many 541:544 arg1 metapneumo- 606:616 metapneumo- 606:616 metapneumo- 606:616 The paramyxovirus family includes many important pathogens, such as measles, mumps, parainfluenza, metapneumo- and the deadly Henipaviruses Nipah (NiV) and Hendra (HeV) viruses. 26867212 4 39 theme many 541:544 arg1 NiV 654:656 the deadly Henipaviruses Nipah (NiV) and Hendra (HeV) viruses 622:682 NiV 654:656 The paramyxovirus family includes many important pathogens, such as measles, mumps, parainfluenza, metapneumo- and the deadly Henipaviruses Nipah (NiV) and Hendra (HeV) viruses. 26867212 4 39 theme many 541:544 arg1 measles 575:581 measles 575:581 measles 575:581 The paramyxovirus family includes many important pathogens, such as measles, mumps, parainfluenza, metapneumo- and the deadly Henipaviruses Nipah (NiV) and Hendra (HeV) viruses. 26867212 10 40 theme O-glycans 1492:1500 arg1 functions 1465:1473 multiple novel and pathologically important functions 1421:1473 multiple novel and pathologically important functions of paramyxoviral O-glycans 1421:1500 Thus our results identify multiple novel and pathologically important functions of paramyxoviral O-glycans, paving the way to study O-glycan functions in other paramyxoviruses and enveloped viruses. 26867212 5 41 gly glycoproteins 765:777 arg1 glycoproteins 765:777 two viral membrane glycoproteins 746:777 two viral membrane glycoproteins: the attachment (HN/H/G) and fusion (F) glycoproteins 746:831 Paramyxoviral cell entry requires the coordinated actions of two viral membrane glycoproteins: the attachment (HN/H/G) and fusion (F) glycoproteins. 26867212 5 41 gly glycoproteins 765:777 arg1 attachment 784:793 the attachment 780:793 the attachment (HN/H/G) 780:802 Paramyxoviral cell entry requires the coordinated actions of two viral membrane glycoproteins: the attachment (HN/H/G) and fusion (F) glycoproteins. 26867212 5 41 gly glycoproteins 765:777 arg1 fusion 808:813 fusion 808:813 fusion (F) 808:817 Paramyxoviral cell entry requires the coordinated actions of two viral membrane glycoproteins: the attachment (HN/H/G) and fusion (F) glycoproteins. 26867212 0 42 dep Functions 15:23 arg1 Functions 70:78 The First O-glycan Functions 51:78 Multiple Novel Functions of Henipavirus O-glycans: The First O-glycan Functions Identified in the Paramyxovirus Family. 0:118 Multiple Novel Functions of Henipavirus O-glycans: The First O-glycan Functions Identified in the Paramyxovirus Family. 26867212 7 43 from phenotypes 1257:1266 arg1 system 1167:1172 a pseudotyped viral system 1147:1172 a pseudotyped viral system 1147:1172 We mutated the identified HeV G O-glycosylation sites and found mutants with altered cell-cell fusion, G conformation, G/F association, viral entry in a pseudotyped viral system, and, quite unexpectedly, pseudotyped viral F protein incorporation and processing phenotypes. 26867212 7 44 theme pseudotyped 1200:1210 arg1 incorporation 1228:1240 pseudotyped viral F protein incorporation 1200:1240 pseudotyped viral F protein incorporation 1200:1240 We mutated the identified HeV G O-glycosylation sites and found mutants with altered cell-cell fusion, G conformation, G/F association, viral entry in a pseudotyped viral system, and, quite unexpectedly, pseudotyped viral F protein incorporation and processing phenotypes. 26867212 7 45 theme altered 1073:1079 arg1 fusion 1091:1096 altered cell-cell fusion 1073:1096 altered cell-cell fusion 1073:1096 We mutated the identified HeV G O-glycosylation sites and found mutants with altered cell-cell fusion, G conformation, G/F association, viral entry in a pseudotyped viral system, and, quite unexpectedly, pseudotyped viral F protein incorporation and processing phenotypes. 26867212 10 46 theme other 1549:1553 arg1 paramyxoviruses 1555:1569 other paramyxoviruses 1549:1569 other paramyxoviruses 1549:1569 Thus our results identify multiple novel and pathologically important functions of paramyxoviral O-glycans, paving the way to study O-glycan functions in other paramyxoviruses and enveloped viruses. 26867212 2 47 theme host 295:298 arg1 invasion 300:307 host invasion 295:307 host invasion 295:307 Both microbial and host protein glycans are used by many pathogens for host invasion and immune evasion, yet little is known about the roles of O-glycans in viral pathogenesis. 26867212 9 48 theme NiV 1382:1384 arg1 mutants 1386:1392 equivalent NiV mutants 1371:1392 equivalent NiV mutants 1371:1392 These phenotypes were broadly conserved for equivalent NiV mutants. 26867212 2 49 used used 268:271 arg2 glycans 256:262 Both microbial and host protein glycans 224:262 Both microbial and host protein glycans 224:262 Both microbial and host protein glycans are used by many pathogens for host invasion and immune evasion, yet little is known about the roles of O-glycans in viral pathogenesis. 26867212 2 50 dep glycans 256:262 arg1 host 243:246 host 243:246 host 243:246 Both microbial and host protein glycans are used by many pathogens for host invasion and immune evasion, yet little is known about the roles of O-glycans in viral pathogenesis. 26867212 2 50 dep glycans 256:262 arg1 Both 224:227 Both 224:227 Both 224:227 Both microbial and host protein glycans are used by many pathogens for host invasion and immune evasion, yet little is known about the roles of O-glycans in viral pathogenesis. 26867212 7 51 theme viral 1161:1165 arg1 system 1167:1172 a pseudotyped viral system 1147:1172 a pseudotyped viral system 1147:1172 We mutated the identified HeV G O-glycosylation sites and found mutants with altered cell-cell fusion, G conformation, G/F association, viral entry in a pseudotyped viral system, and, quite unexpectedly, pseudotyped viral F protein incorporation and processing phenotypes. 26867212 7 52 theme O-glycosylation 1028:1042 arg1 sites 1044:1048 the identified HeV G O-glycosylation sites 1007:1048 the identified HeV G O-glycosylation sites 1007:1048 We mutated the identified HeV G O-glycosylation sites and found mutants with altered cell-cell fusion, G conformation, G/F association, viral entry in a pseudotyped viral system, and, quite unexpectedly, pseudotyped viral F protein incorporation and processing phenotypes. 26867212 5 53 dep glycoproteins 765:777 arg1 F 816:816 F 816:816 F 816:816 Paramyxoviral cell entry requires the coordinated actions of two viral membrane glycoproteins: the attachment (HN/H/G) and fusion (F) glycoproteins. 26867212 5 53 dep glycoproteins 765:777 arg1 HN/H/G 796:801 HN/H/G 796:801 HN/H/G 796:801 Paramyxoviral cell entry requires the coordinated actions of two viral membrane glycoproteins: the attachment (HN/H/G) and fusion (F) glycoproteins. 26867212 5 53 dep glycoproteins 765:777 arg1 fusion 808:813 fusion 808:813 fusion (F) 808:817 Paramyxoviral cell entry requires the coordinated actions of two viral membrane glycoproteins: the attachment (HN/H/G) and fusion (F) glycoproteins. 26867212 5 53 dep glycoproteins 765:777 arg1 attachment 784:793 the attachment 780:793 the attachment (HN/H/G) 780:802 Paramyxoviral cell entry requires the coordinated actions of two viral membrane glycoproteins: the attachment (HN/H/G) and fusion (F) glycoproteins. 26867212 5 53 dep glycoproteins 765:777 arg1 glycoproteins 765:777 two viral membrane glycoproteins 746:777 two viral membrane glycoproteins: the attachment (HN/H/G) and fusion (F) glycoproteins 746:831 Paramyxoviral cell entry requires the coordinated actions of two viral membrane glycoproteins: the attachment (HN/H/G) and fusion (F) glycoproteins. 26867212 2 54 from roles 359:363 arg1 pathogenesis 387:398 viral pathogenesis 381:398 viral pathogenesis 381:398 Both microbial and host protein glycans are used by many pathogens for host invasion and immune evasion, yet little is known about the roles of O-glycans in viral pathogenesis. 26867212 7 55 gly O-glycosylation 1028:1042 arg2 sites 1044:1048 the identified HeV G O-glycosylation sites 1007:1048 the identified HeV G O-glycosylation sites 1007:1048 We mutated the identified HeV G O-glycosylation sites and found mutants with altered cell-cell fusion, G conformation, G/F association, viral entry in a pseudotyped viral system, and, quite unexpectedly, pseudotyped viral F protein incorporation and processing phenotypes. 26867212 7 56 theme HeV 1022:1024 arg1 sites 1044:1048 the identified HeV G O-glycosylation sites 1007:1048 the identified HeV G O-glycosylation sites 1007:1048 We mutated the identified HeV G O-glycosylation sites and found mutants with altered cell-cell fusion, G conformation, G/F association, viral entry in a pseudotyped viral system, and, quite unexpectedly, pseudotyped viral F protein incorporation and processing phenotypes. 26867212 1 57 theme several 206:212 arg1 kingdoms 214:221 several kingdoms 206:221 several kingdoms 206:221 O-linked glycosylation is a ubiquitous protein modification in organisms belonging to several kingdoms. 26867212 6 58 theme protein 919:925 arg1 use 897:899 use 897:899 use of the attachment protein of this deadly paramyxovirus 897:954 O-glycan sites in HeV G were recently identified, facilitating use of the attachment protein of this deadly paramyxovirus as a model to study O-glycan functions. 26867212 6 58 theme protein 919:925 arg1 model 961:965 a model 959:965 a model to study O-glycan functions 959:993 O-glycan sites in HeV G were recently identified, facilitating use of the attachment protein of this deadly paramyxovirus as a model to study O-glycan functions. 26867212 5 59 theme Paramyxoviral 685:697 arg1 entry 704:708 Paramyxoviral cell entry 685:708 Paramyxoviral cell entry 685:708 Paramyxoviral cell entry requires the coordinated actions of two viral membrane glycoproteins: the attachment (HN/H/G) and fusion (F) glycoproteins. 26867212 2 60 theme protein 248:254 arg1 glycans 256:262 Both microbial and host protein glycans 224:262 Both microbial and host protein glycans 224:262 Both microbial and host protein glycans are used by many pathogens for host invasion and immune evasion, yet little is known about the roles of O-glycans in viral pathogenesis. 26867212 4 61 theme Henipaviruses 633:645 arg1 NiV 654:656 the deadly Henipaviruses Nipah (NiV) and Hendra (HeV) viruses 622:682 NiV 654:656 The paramyxovirus family includes many important pathogens, such as measles, mumps, parainfluenza, metapneumo- and the deadly Henipaviruses Nipah (NiV) and Hendra (HeV) viruses. 26867212 0 62 theme O-glycans 40:48 arg1 Functions 15:23 Multiple Novel Functions 0:23 Multiple Novel Functions of Henipavirus O-glycans: The First O-glycan Functions Identified in the Paramyxovirus Family. 0:118 Multiple Novel Functions of Henipavirus O-glycans: The First O-glycan Functions Identified in the Paramyxovirus Family. 26867212 6 63 theme O-glycan 976:983 arg1 functions 985:993 O-glycan functions 976:993 O-glycan functions 976:993 O-glycan sites in HeV G were recently identified, facilitating use of the attachment protein of this deadly paramyxovirus as a model to study O-glycan functions. 26867212 0 64 theme O-glycan 61:68 arg1 Functions 70:78 The First O-glycan Functions 51:78 Multiple Novel Functions of Henipavirus O-glycans: The First O-glycan Functions Identified in the Paramyxovirus Family. 0:118 Multiple Novel Functions of Henipavirus O-glycans: The First O-glycan Functions Identified in the Paramyxovirus Family. 26867212 7 65 from fusion 1091:1096 arg1 system 1167:1172 a pseudotyped viral system 1147:1172 a pseudotyped viral system 1147:1172 We mutated the identified HeV G O-glycosylation sites and found mutants with altered cell-cell fusion, G conformation, G/F association, viral entry in a pseudotyped viral system, and, quite unexpectedly, pseudotyped viral F protein incorporation and processing phenotypes. 26867212 4 66 theme Hendra 663:668 arg1 viruses 676:682 the deadly Henipaviruses Nipah (NiV) and Hendra (HeV) viruses 622:682 viruses 676:682 The paramyxovirus family includes many important pathogens, such as measles, mumps, parainfluenza, metapneumo- and the deadly Henipaviruses Nipah (NiV) and Hendra (HeV) viruses. 26867212 7 67 theme pseudotyped 1149:1159 arg1 system 1167:1172 a pseudotyped viral system 1147:1172 a pseudotyped viral system 1147:1172 We mutated the identified HeV G O-glycosylation sites and found mutants with altered cell-cell fusion, G conformation, G/F association, viral entry in a pseudotyped viral system, and, quite unexpectedly, pseudotyped viral F protein incorporation and processing phenotypes. 26867212 10 68 theme paramyxoviral 1478:1490 arg1 O-glycans 1492:1500 paramyxoviral O-glycans 1478:1500 paramyxoviral O-glycans 1478:1500 Thus our results identify multiple novel and pathologically important functions of paramyxoviral O-glycans, paving the way to study O-glycan functions in other paramyxoviruses and enveloped viruses. 26867212 1 69 theme protein 159:165 arg1 glycosylation 129:141 O-linked glycosylation 120:141 O-linked glycosylation 120:141 O-linked glycosylation is a ubiquitous protein modification in organisms belonging to several kingdoms. 26867212 1 69 theme protein 159:165 arg1 modification 167:178 a ubiquitous protein modification 146:178 a ubiquitous protein modification in organisms belonging to several kingdoms 146:221 O-linked glycosylation is a ubiquitous protein modification in organisms belonging to several kingdoms. 26867212 4 70 theme paramyxovirus 511:523 arg1 family 525:530 The paramyxovirus family 507:530 The paramyxovirus family 507:530 The paramyxovirus family includes many important pathogens, such as measles, mumps, parainfluenza, metapneumo- and the deadly Henipaviruses Nipah (NiV) and Hendra (HeV) viruses. 26867212 4 71 theme HeV 671:673 arg1 viruses 676:682 the deadly Henipaviruses Nipah (NiV) and Hendra (HeV) viruses 622:682 viruses 676:682 The paramyxovirus family includes many important pathogens, such as measles, mumps, parainfluenza, metapneumo- and the deadly Henipaviruses Nipah (NiV) and Hendra (HeV) viruses. 26867212 1 72 from modification 167:178 arg1 organisms 183:191 organisms 183:191 organisms belonging to several kingdoms 183:221 O-linked glycosylation is a ubiquitous protein modification in organisms belonging to several kingdoms. 26867212 6 73 theme paramyxovirus 942:954 arg1 use 897:899 use 897:899 use of the attachment protein of this deadly paramyxovirus 897:954 O-glycan sites in HeV G were recently identified, facilitating use of the attachment protein of this deadly paramyxovirus as a model to study O-glycan functions. 26867212 6 73 theme paramyxovirus 942:954 arg1 model 961:965 a model 959:965 a model to study O-glycan functions 959:993 O-glycan sites in HeV G were recently identified, facilitating use of the attachment protein of this deadly paramyxovirus as a model to study O-glycan functions. 26867212 7 74 theme viral 1132:1136 arg1 entry 1138:1142 viral entry 1132:1142 viral entry in a pseudotyped viral system 1132:1172 We mutated the identified HeV G O-glycosylation sites and found mutants with altered cell-cell fusion, G conformation, G/F association, viral entry in a pseudotyped viral system, and, quite unexpectedly, pseudotyped viral F protein incorporation and processing phenotypes. 26867212 7 75 from association 1119:1129 arg1 system 1167:1172 a pseudotyped viral system 1147:1172 a pseudotyped viral system 1147:1172 We mutated the identified HeV G O-glycosylation sites and found mutants with altered cell-cell fusion, G conformation, G/F association, viral entry in a pseudotyped viral system, and, quite unexpectedly, pseudotyped viral F protein incorporation and processing phenotypes. 26867212 10 76 theme novel 1430:1434 arg1 functions 1465:1473 multiple novel and pathologically important functions 1421:1473 multiple novel and pathologically important functions of paramyxoviral O-glycans 1421:1500 Thus our results identify multiple novel and pathologically important functions of paramyxoviral O-glycans, paving the way to study O-glycan functions in other paramyxoviruses and enveloped viruses. 26867212 3 77 theme single 425:430 arg1 function 432:439 no single function 422:439 no single function attributed to O-glycans for the significant paramyxovirus family 422:504 Reportedly, there is no single function attributed to O-glycans for the significant paramyxovirus family. 26867212 0 78 theme Novel 9:13 arg1 Functions 15:23 Multiple Novel Functions 0:23 Multiple Novel Functions of Henipavirus O-glycans: The First O-glycan Functions Identified in the Paramyxovirus Family. 0:118 Multiple Novel Functions of Henipavirus O-glycans: The First O-glycan Functions Identified in the Paramyxovirus Family. 26867212 8 79 theme viral 1306:1310 arg1 glycoproteins 1312:1324 viral glycoproteins 1306:1324 viral glycoproteins 1306:1324 These are all important functions of viral glycoproteins. 26867212 7 80 theme G 1099:1099 arg1 conformation 1101:1112 G conformation 1099:1112 G conformation 1099:1112 We mutated the identified HeV G O-glycosylation sites and found mutants with altered cell-cell fusion, G conformation, G/F association, viral entry in a pseudotyped viral system, and, quite unexpectedly, pseudotyped viral F protein incorporation and processing phenotypes. 26867212 7 81 theme protein 1220:1226 arg1 incorporation 1228:1240 pseudotyped viral F protein incorporation 1200:1240 pseudotyped viral F protein incorporation 1200:1240 We mutated the identified HeV G O-glycosylation sites and found mutants with altered cell-cell fusion, G conformation, G/F association, viral entry in a pseudotyped viral system, and, quite unexpectedly, pseudotyped viral F protein incorporation and processing phenotypes. 26867212 0 82 theme Paramyxovirus 98:110 arg1 Family 112:117 the Paramyxovirus Family 94:117 the Paramyxovirus Family 94:117 Multiple Novel Functions of Henipavirus O-glycans: The First O-glycan Functions Identified in the Paramyxovirus Family. 26867212 8 83 gly glycoproteins 1312:1324 arg1 glycoproteins 1312:1324 viral glycoproteins 1306:1324 viral glycoproteins 1306:1324 These are all important functions of viral glycoproteins. 26867212 7 84 from incorporation 1228:1240 arg1 system 1167:1172 a pseudotyped viral system 1147:1172 a pseudotyped viral system 1147:1172 We mutated the identified HeV G O-glycosylation sites and found mutants with altered cell-cell fusion, G conformation, G/F association, viral entry in a pseudotyped viral system, and, quite unexpectedly, pseudotyped viral F protein incorporation and processing phenotypes. 26867212 7 85 theme viral 1212:1216 arg1 incorporation 1228:1240 pseudotyped viral F protein incorporation 1200:1240 pseudotyped viral F protein incorporation 1200:1240 We mutated the identified HeV G O-glycosylation sites and found mutants with altered cell-cell fusion, G conformation, G/F association, viral entry in a pseudotyped viral system, and, quite unexpectedly, pseudotyped viral F protein incorporation and processing phenotypes. 26867212 7 86 theme identified 1011:1020 arg1 sites 1044:1048 the identified HeV G O-glycosylation sites 1007:1048 the identified HeV G O-glycosylation sites 1007:1048 We mutated the identified HeV G O-glycosylation sites and found mutants with altered cell-cell fusion, G conformation, G/F association, viral entry in a pseudotyped viral system, and, quite unexpectedly, pseudotyped viral F protein incorporation and processing phenotypes. 26867212 4 87 theme important 546:554 arg1 mumps 584:588 mumps 584:588 mumps 584:588 The paramyxovirus family includes many important pathogens, such as measles, mumps, parainfluenza, metapneumo- and the deadly Henipaviruses Nipah (NiV) and Hendra (HeV) viruses. 26867212 4 87 theme important 546:554 arg1 pathogens 556:564 many important pathogens 541:564 many important pathogens 541:564 The paramyxovirus family includes many important pathogens, such as measles, mumps, parainfluenza, metapneumo- and the deadly Henipaviruses Nipah (NiV) and Hendra (HeV) viruses. 26867212 4 87 theme important 546:554 arg1 parainfluenza 591:603 parainfluenza 591:603 parainfluenza 591:603 The paramyxovirus family includes many important pathogens, such as measles, mumps, parainfluenza, metapneumo- and the deadly Henipaviruses Nipah (NiV) and Hendra (HeV) viruses. 26867212 4 87 theme important 546:554 arg1 metapneumo- 606:616 metapneumo- 606:616 metapneumo- 606:616 The paramyxovirus family includes many important pathogens, such as measles, mumps, parainfluenza, metapneumo- and the deadly Henipaviruses Nipah (NiV) and Hendra (HeV) viruses. 26867212 4 87 theme important 546:554 arg1 NiV 654:656 the deadly Henipaviruses Nipah (NiV) and Hendra (HeV) viruses 622:682 NiV 654:656 The paramyxovirus family includes many important pathogens, such as measles, mumps, parainfluenza, metapneumo- and the deadly Henipaviruses Nipah (NiV) and Hendra (HeV) viruses. 26867212 4 87 theme important 546:554 arg1 measles 575:581 measles 575:581 measles 575:581 The paramyxovirus family includes many important pathogens, such as measles, mumps, parainfluenza, metapneumo- and the deadly Henipaviruses Nipah (NiV) and Hendra (HeV) viruses. 26867212 3 88 theme paramyxovirus 485:497 arg1 family 499:504 the significant paramyxovirus family 469:504 the significant paramyxovirus family 469:504 Reportedly, there is no single function attributed to O-glycans for the significant paramyxovirus family. 26867212 1 89 link O-linked 120:127 arg1 glycosylation 129:141 O-linked glycosylation 120:141 O-linked glycosylation 120:141 O-linked glycosylation is a ubiquitous protein modification in organisms belonging to several kingdoms. 26867212 1 89 link O-linked 120:127 arg1 modification 167:178 a ubiquitous protein modification 146:178 a ubiquitous protein modification in organisms belonging to several kingdoms 146:221 O-linked glycosylation is a ubiquitous protein modification in organisms belonging to several kingdoms. 26867212 7 90 with mutants 1060:1066 arg1 association 1119:1129 G/F association 1115:1129 G/F association 1115:1129 We mutated the identified HeV G O-glycosylation sites and found mutants with altered cell-cell fusion, G conformation, G/F association, viral entry in a pseudotyped viral system, and, quite unexpectedly, pseudotyped viral F protein incorporation and processing phenotypes. 26867212 7 90 with mutants 1060:1066 arg1 incorporation 1228:1240 pseudotyped viral F protein incorporation 1200:1240 pseudotyped viral F protein incorporation 1200:1240 We mutated the identified HeV G O-glycosylation sites and found mutants with altered cell-cell fusion, G conformation, G/F association, viral entry in a pseudotyped viral system, and, quite unexpectedly, pseudotyped viral F protein incorporation and processing phenotypes. 26867212 7 90 with mutants 1060:1066 arg1 fusion 1091:1096 altered cell-cell fusion 1073:1096 altered cell-cell fusion 1073:1096 We mutated the identified HeV G O-glycosylation sites and found mutants with altered cell-cell fusion, G conformation, G/F association, viral entry in a pseudotyped viral system, and, quite unexpectedly, pseudotyped viral F protein incorporation and processing phenotypes. 26867212 7 90 with mutants 1060:1066 arg1 conformation 1101:1112 G conformation 1099:1112 G conformation 1099:1112 We mutated the identified HeV G O-glycosylation sites and found mutants with altered cell-cell fusion, G conformation, G/F association, viral entry in a pseudotyped viral system, and, quite unexpectedly, pseudotyped viral F protein incorporation and processing phenotypes. 26867212 7 90 with mutants 1060:1066 arg1 entry 1138:1142 viral entry 1132:1142 viral entry in a pseudotyped viral system 1132:1172 We mutated the identified HeV G O-glycosylation sites and found mutants with altered cell-cell fusion, G conformation, G/F association, viral entry in a pseudotyped viral system, and, quite unexpectedly, pseudotyped viral F protein incorporation and processing phenotypes. 26867212 7 90 with mutants 1060:1066 arg1 phenotypes 1257:1266 processing phenotypes 1246:1266 processing phenotypes 1246:1266 We mutated the identified HeV G O-glycosylation sites and found mutants with altered cell-cell fusion, G conformation, G/F association, viral entry in a pseudotyped viral system, and, quite unexpectedly, pseudotyped viral F protein incorporation and processing phenotypes. 26867212 2 91 dep Both 224:227 arg1 microbial 229:237 microbial 229:237 microbial 229:237 Both microbial and host protein glycans are used by many pathogens for host invasion and immune evasion, yet little is known about the roles of O-glycans in viral pathogenesis. 24403531 2 0 theme amino 458:462 arg1 identity 478:485 virtually no amino acid sequence identity 445:485 virtually no amino acid sequence identity 445:485 Ly49B displays substantial sequence divergence from other Ly49s and in particular shares virtually no amino acid sequence identity with the residues that have been reported to bind to MHC class I (cI) ligands in other Ly49s. 24403531 1 1 theme family 301:306 arg1 Ly49B 167:171 Ly49B 167:171 Ly49B 167:171 Ly49B is a potentially important immunoregulator expressed on mouse myeloid cells, and it is thus an unusual member of the wider Ly49 family whose members are ordinarily found on NK cells. 24403531 1 1 theme family 301:306 arg1 it 254:255 it 254:255 it 254:255 Ly49B is a potentially important immunoregulator expressed on mouse myeloid cells, and it is thus an unusual member of the wider Ly49 family whose members are ordinarily found on NK cells. 24403531 1 1 theme family 301:306 arg1 member 276:281 an unusual member 265:281 an unusual member of the wider Ly49 family whose members are ordinarily found on NK cells 265:353 Ly49B is a potentially important immunoregulator expressed on mouse myeloid cells, and it is thus an unusual member of the wider Ly49 family whose members are ordinarily found on NK cells. 24403531 1 1 theme family 301:306 arg1 immunoregulator 200:214 a potentially important immunoregulator 176:214 a potentially important immunoregulator expressed on mouse myeloid cells 176:247 Ly49B is a potentially important immunoregulator expressed on mouse myeloid cells, and it is thus an unusual member of the wider Ly49 family whose members are ordinarily found on NK cells. 24403531 2 2 theme MHC 540:542 arg1 class 544:548 MHC class I 540:550 MHC class I (cI) ligands 540:563 Ly49B displays substantial sequence divergence from other Ly49s and in particular shares virtually no amino acid sequence identity with the residues that have been reported to bind to MHC class I (cI) ligands in other Ly49s. 24403531 2 2 theme MHC 540:542 arg1 cI 553:554 cI 553:554 cI 553:554 Ly49B displays substantial sequence divergence from other Ly49s and in particular shares virtually no amino acid sequence identity with the residues that have been reported to bind to MHC class I (cI) ligands in other Ly49s. 24403531 2 3 theme no 455:456 arg1 identity 478:485 virtually no amino acid sequence identity 445:485 virtually no amino acid sequence identity 445:485 Ly49B displays substantial sequence divergence from other Ly49s and in particular shares virtually no amino acid sequence identity with the residues that have been reported to bind to MHC class I (cI) ligands in other Ly49s. 24403531 0 4 theme Ly49s 160:164 arg1 evolution 147:155 the molecular evolution 133:155 the molecular evolution of Ly49s 133:164 Mutagenesis of Ly49B reveals key structural elements required for promiscuous binding to MHC class I molecules and new insights into the molecular evolution of Ly49s. 24403531 8 5 theme acid 1535:1538 arg1 changes 1540:1546 amino acid changes 1529:1546 amino acid changes 1529:1546 Remarkably, however, Ly49B(BALB) variants that have C57 residues at positions 166 or 167, and are unable to bind cI multimers, regain substantial cI binding when amino acid changes are made at distal positions, providing an explanation of how highly divergent Ly49s that retain the ability to bind cI molecules might have evolved. 24403531 1 6 located found 337:341 arg2 members 314:320 members 314:320 members 314:320 Ly49B is a potentially important immunoregulator expressed on mouse myeloid cells, and it is thus an unusual member of the wider Ly49 family whose members are ordinarily found on NK cells. 24403531 1 6 located found 337:341 arg1 cells 349:353 NK cells 346:353 NK cells 346:353 Ly49B is a potentially important immunoregulator expressed on mouse myeloid cells, and it is thus an unusual member of the wider Ly49 family whose members are ordinarily found on NK cells. 24403531 5 7 theme Ly49s 1115:1119 arg1 region 1105:1110 the C-terminal region 1090:1110 the C-terminal region of Ly49s 1090:1119 However, transfer of these C-terminal 20 aa to Ly49A inhibited cI binding, as did the addition of a hemagglutinin tag to the C terminus of Ly49B, demonstrating unexpectedly that the C-terminal region of Ly49s can play a significant role in ligand binding. 24403531 5 8 theme Ly49B 1051:1055 arg1 terminus 1039:1046 the C terminus 1033:1046 the C terminus of Ly49B 1033:1055 However, transfer of these C-terminal 20 aa to Ly49A inhibited cI binding, as did the addition of a hemagglutinin tag to the C terminus of Ly49B, demonstrating unexpectedly that the C-terminal region of Ly49s can play a significant role in ligand binding. 24403531 0 9 theme class 93:97 arg1 molecules 101:109 MHC class I molecules 89:109 MHC class I molecules 89:109 Mutagenesis of Ly49B reveals key structural elements required for promiscuous binding to MHC class I molecules and new insights into the molecular evolution of Ly49s. 24403531 2 10 from Ly49s 414:418 arg1 divergence 392:401 substantial sequence divergence 371:401 substantial sequence divergence from other Ly49s 371:418 Ly49B displays substantial sequence divergence from other Ly49s and in particular shares virtually no amino acid sequence identity with the residues that have been reported to bind to MHC class I (cI) ligands in other Ly49s. 24403531 4 11 theme predicted 775:783 arg1 sites 808:812 the four predicted N-linked glycosylation sites 766:812 the four predicted N-linked glycosylation sites of Ly49B 766:821 Binding was not significantly affected by inactivation of any of the four predicted N-linked glycosylation sites of Ly49B, nor was it affected by removal of the unique 20-aa C-terminal extension found in Ly49B. 24403531 4 11 theme predicted 775:783 arg1 Ly49B 817:821 Ly49B 817:821 Ly49B 817:821 Binding was not significantly affected by inactivation of any of the four predicted N-linked glycosylation sites of Ly49B, nor was it affected by removal of the unique 20-aa C-terminal extension found in Ly49B. 24403531 8 12 theme amino 1529:1533 arg1 changes 1540:1546 amino acid changes 1529:1546 amino acid changes 1529:1546 Remarkably, however, Ly49B(BALB) variants that have C57 residues at positions 166 or 167, and are unable to bind cI multimers, regain substantial cI binding when amino acid changes are made at distal positions, providing an explanation of how highly divergent Ly49s that retain the ability to bind cI molecules might have evolved. 24403531 4 13 theme unique 862:867 arg1 extension 886:894 the unique 20-aa C-terminal extension 858:894 the unique 20-aa C-terminal extension found in Ly49B 858:909 Binding was not significantly affected by inactivation of any of the four predicted N-linked glycosylation sites of Ly49B, nor was it affected by removal of the unique 20-aa C-terminal extension found in Ly49B. 24403531 0 14 theme MHC 89:91 arg1 molecules 101:109 MHC class I molecules 89:109 MHC class I molecules 89:109 Mutagenesis of Ly49B reveals key structural elements required for promiscuous binding to MHC class I molecules and new insights into the molecular evolution of Ly49s. 24403531 2 15 theme class 544:548 arg1 ligands 557:563 MHC class I (cI) ligands 540:563 MHC class I (cI) ligands 540:563 Ly49B displays substantial sequence divergence from other Ly49s and in particular shares virtually no amino acid sequence identity with the residues that have been reported to bind to MHC class I (cI) ligands in other Ly49s. 24403531 8 16 theme BALB 1394:1397 arg1 variants 1400:1407 Ly49B(BALB) variants 1388:1407 Ly49B(BALB) variants 1388:1407 Remarkably, however, Ly49B(BALB) variants that have C57 residues at positions 166 or 167, and are unable to bind cI multimers, regain substantial cI binding when amino acid changes are made at distal positions, providing an explanation of how highly divergent Ly49s that retain the ability to bind cI molecules might have evolved. 24403531 6 17 theme BALB/c 1191:1196 arg1 residues 1206:1213 BALB/c and C57 residues 1191:1213 residues 1206:1213 Systematic exchange of BALB/c and C57 residues revealed that Trp(166), Asn(167), and Cys(251) are of major importance for cI binding in Ly49B. 24403531 6 18 theme C57 1202:1204 arg1 residues 1206:1213 BALB/c and C57 residues 1191:1213 residues 1206:1213 Systematic exchange of BALB/c and C57 residues revealed that Trp(166), Asn(167), and Cys(251) are of major importance for cI binding in Ly49B. 24403531 2 19 theme other 568:572 arg1 Ly49s 574:578 other Ly49s 568:578 other Ly49s 568:578 Ly49B displays substantial sequence divergence from other Ly49s and in particular shares virtually no amino acid sequence identity with the residues that have been reported to bind to MHC class I (cI) ligands in other Ly49s. 24403531 8 20 theme C57 1419:1421 arg1 residues 1423:1430 C57 residues 1419:1430 C57 residues at positions 166 or 167 1419:1454 Remarkably, however, Ly49B(BALB) variants that have C57 residues at positions 166 or 167, and are unable to bind cI multimers, regain substantial cI binding when amino acid changes are made at distal positions, providing an explanation of how highly divergent Ly49s that retain the ability to bind cI molecules might have evolved. 24403531 4 21 link N-linked 785:792 arg1 sites 808:812 the four predicted N-linked glycosylation sites 766:812 the four predicted N-linked glycosylation sites of Ly49B 766:821 Binding was not significantly affected by inactivation of any of the four predicted N-linked glycosylation sites of Ly49B, nor was it affected by removal of the unique 20-aa C-terminal extension found in Ly49B. 24403531 4 21 link N-linked 785:792 arg1 Ly49B 817:821 Ly49B 817:821 Ly49B 817:821 Binding was not significantly affected by inactivation of any of the four predicted N-linked glycosylation sites of Ly49B, nor was it affected by removal of the unique 20-aa C-terminal extension found in Ly49B. 24403531 3 22 theme BALB/c 626:631 arg1 isoform 651:657 the BALB/c, but not the C57, isoform 622:657 the BALB/c, but not the C57, isoform of Ly49B 622:666 Despite this, we show in this study that the BALB/c, but not the C57, isoform of Ly49B displays promiscuous cI binding. 24403531 4 23 theme extension 886:894 arg1 removal 847:853 removal 847:853 removal of the unique 20-aa C-terminal extension found in Ly49B 847:909 Binding was not significantly affected by inactivation of any of the four predicted N-linked glycosylation sites of Ly49B, nor was it affected by removal of the unique 20-aa C-terminal extension found in Ly49B. 24403531 5 24 theme hemagglutinin 1012:1024 arg1 tag 1026:1028 a hemagglutinin tag 1010:1028 a hemagglutinin tag 1010:1028 However, transfer of these C-terminal 20 aa to Ly49A inhibited cI binding, as did the addition of a hemagglutinin tag to the C terminus of Ly49B, demonstrating unexpectedly that the C-terminal region of Ly49s can play a significant role in ligand binding. 24403531 3 25 theme C57 646:648 arg1 isoform 651:657 the BALB/c, but not the C57, isoform 622:657 the BALB/c, but not the C57, isoform of Ly49B 622:666 Despite this, we show in this study that the BALB/c, but not the C57, isoform of Ly49B displays promiscuous cI binding. 24403531 4 26 theme any 759:761 arg1 inactivation 743:754 inactivation 743:754 inactivation of any of the four predicted N-linked glycosylation sites of Ly49B 743:821 Binding was not significantly affected by inactivation of any of the four predicted N-linked glycosylation sites of Ly49B, nor was it affected by removal of the unique 20-aa C-terminal extension found in Ly49B. 24403531 0 27 theme promiscuous 66:76 arg1 binding 78:84 promiscuous binding 66:84 promiscuous binding to MHC class I molecules 66:109 Mutagenesis of Ly49B reveals key structural elements required for promiscuous binding to MHC class I molecules and new insights into the molecular evolution of Ly49s. 24403531 6 28 theme residues 1206:1213 arg1 exchange 1179:1186 Systematic exchange 1168:1186 Systematic exchange of BALB/c and C57 residues 1168:1213 Systematic exchange of BALB/c and C57 residues revealed that Trp(166), Asn(167), and Cys(251) are of major importance for cI binding in Ly49B. 24403531 5 29 theme tag 1026:1028 arg1 addition 998:1005 the addition 994:1005 the addition of a hemagglutinin tag to the C terminus of Ly49B 994:1055 However, transfer of these C-terminal 20 aa to Ly49A inhibited cI binding, as did the addition of a hemagglutinin tag to the C terminus of Ly49B, demonstrating unexpectedly that the C-terminal region of Ly49s can play a significant role in ligand binding. 24403531 4 30 located found 896:900 arg2 extension 886:894 the unique 20-aa C-terminal extension 858:894 the unique 20-aa C-terminal extension found in Ly49B 858:909 Binding was not significantly affected by inactivation of any of the four predicted N-linked glycosylation sites of Ly49B, nor was it affected by removal of the unique 20-aa C-terminal extension found in Ly49B. 24403531 4 30 located found 896:900 arg1 Ly49B 905:909 Ly49B 905:909 Ly49B 905:909 Binding was not significantly affected by inactivation of any of the four predicted N-linked glycosylation sites of Ly49B, nor was it affected by removal of the unique 20-aa C-terminal extension found in Ly49B. 24403531 8 31 contain have 1414:1417 arg1 variants 1400:1407 Ly49B(BALB) variants 1388:1407 Ly49B(BALB) variants 1388:1407 Remarkably, however, Ly49B(BALB) variants that have C57 residues at positions 166 or 167, and are unable to bind cI multimers, regain substantial cI binding when amino acid changes are made at distal positions, providing an explanation of how highly divergent Ly49s that retain the ability to bind cI molecules might have evolved. 24403531 8 31 contain have 1414:1417 arg2 residues 1423:1430 C57 residues 1419:1430 C57 residues at positions 166 or 167 1419:1454 Remarkably, however, Ly49B(BALB) variants that have C57 residues at positions 166 or 167, and are unable to bind cI multimers, regain substantial cI binding when amino acid changes are made at distal positions, providing an explanation of how highly divergent Ly49s that retain the ability to bind cI molecules might have evolved. 24403531 5 32 theme aa 953:954 arg1 transfer 921:928 transfer 921:928 transfer of these C-terminal 20 aa to Ly49A 921:963 However, transfer of these C-terminal 20 aa to Ly49A inhibited cI binding, as did the addition of a hemagglutinin tag to the C terminus of Ly49B, demonstrating unexpectedly that the C-terminal region of Ly49s can play a significant role in ligand binding. 24403531 2 33 theme other 408:412 arg1 Ly49s 414:418 other Ly49s 408:418 other Ly49s 408:418 Ly49B displays substantial sequence divergence from other Ly49s and in particular shares virtually no amino acid sequence identity with the residues that have been reported to bind to MHC class I (cI) ligands in other Ly49s. 24403531 3 34 theme cI 689:690 arg1 binding 692:698 promiscuous cI binding 677:698 promiscuous cI binding 677:698 Despite this, we show in this study that the BALB/c, but not the C57, isoform of Ly49B displays promiscuous cI binding. 24403531 0 35 theme new 115:117 arg1 insights 119:126 new insights 115:126 new insights into the molecular evolution of Ly49s 115:164 Mutagenesis of Ly49B reveals key structural elements required for promiscuous binding to MHC class I molecules and new insights into the molecular evolution of Ly49s. 24403531 8 36 theme distal 1560:1565 arg1 positions 1567:1575 distal positions 1560:1575 distal positions 1560:1575 Remarkably, however, Ly49B(BALB) variants that have C57 residues at positions 166 or 167, and are unable to bind cI multimers, regain substantial cI binding when amino acid changes are made at distal positions, providing an explanation of how highly divergent Ly49s that retain the ability to bind cI molecules might have evolved. 24403531 5 37 theme ligand 1152:1157 arg1 binding 1159:1165 ligand binding 1152:1165 ligand binding 1152:1165 However, transfer of these C-terminal 20 aa to Ly49A inhibited cI binding, as did the addition of a hemagglutinin tag to the C terminus of Ly49B, demonstrating unexpectedly that the C-terminal region of Ly49s can play a significant role in ligand binding. 24403531 4 38 theme 20-aa 869:873 arg1 extension 886:894 the unique 20-aa C-terminal extension 858:894 the unique 20-aa C-terminal extension found in Ly49B 858:909 Binding was not significantly affected by inactivation of any of the four predicted N-linked glycosylation sites of Ly49B, nor was it affected by removal of the unique 20-aa C-terminal extension found in Ly49B. 24403531 0 39 theme Ly49B 15:19 arg1 Mutagenesis 0:10 Mutagenesis 0:10 Mutagenesis of Ly49B 0:19 Mutagenesis of Ly49B reveals key structural elements required for promiscuous binding to MHC class I molecules and new insights into the molecular evolution of Ly49s. 24403531 5 40 theme C 1037:1037 arg1 terminus 1039:1046 the C terminus 1033:1046 the C terminus of Ly49B 1033:1055 However, transfer of these C-terminal 20 aa to Ly49A inhibited cI binding, as did the addition of a hemagglutinin tag to the C terminus of Ly49B, demonstrating unexpectedly that the C-terminal region of Ly49s can play a significant role in ligand binding. 24403531 4 41 theme Ly49B 817:821 arg1 sites 808:812 the four predicted N-linked glycosylation sites 766:812 the four predicted N-linked glycosylation sites of Ly49B 766:821 Binding was not significantly affected by inactivation of any of the four predicted N-linked glycosylation sites of Ly49B, nor was it affected by removal of the unique 20-aa C-terminal extension found in Ly49B. 24403531 4 41 theme Ly49B 817:821 arg1 Ly49B 817:821 Ly49B 817:821 Ly49B 817:821 Binding was not significantly affected by inactivation of any of the four predicted N-linked glycosylation sites of Ly49B, nor was it affected by removal of the unique 20-aa C-terminal extension found in Ly49B. 24403531 1 42 theme NK 346:347 arg1 cells 349:353 NK cells 346:353 NK cells 346:353 Ly49B is a potentially important immunoregulator expressed on mouse myeloid cells, and it is thus an unusual member of the wider Ly49 family whose members are ordinarily found on NK cells. 24403531 6 43 from binding 1293:1299 arg1 Ly49B 1304:1308 Ly49B 1304:1308 Ly49B 1304:1308 Systematic exchange of BALB/c and C57 residues revealed that Trp(166), Asn(167), and Cys(251) are of major importance for cI binding in Ly49B. 24403531 6 44 theme cI 1290:1291 arg1 binding 1293:1299 cI binding 1290:1299 cI binding in Ly49B 1290:1308 Systematic exchange of BALB/c and C57 residues revealed that Trp(166), Asn(167), and Cys(251) are of major importance for cI binding in Ly49B. 24403531 2 45 theme sequence 383:390 arg1 divergence 392:401 substantial sequence divergence 371:401 substantial sequence divergence from other Ly49s 371:418 Ly49B displays substantial sequence divergence from other Ly49s and in particular shares virtually no amino acid sequence identity with the residues that have been reported to bind to MHC class I (cI) ligands in other Ly49s. 24403531 0 46 theme structural 33:42 arg1 elements 44:51 key structural elements 29:51 key structural elements required for promiscuous binding to MHC class I molecules and new insights into the molecular evolution of Ly49s 29:164 Mutagenesis of Ly49B reveals key structural elements required for promiscuous binding to MHC class I molecules and new insights into the molecular evolution of Ly49s. 24403531 1 47 theme unusual 268:274 arg1 member 276:281 an unusual member 265:281 an unusual member of the wider Ly49 family whose members are ordinarily found on NK cells 265:353 Ly49B is a potentially important immunoregulator expressed on mouse myeloid cells, and it is thus an unusual member of the wider Ly49 family whose members are ordinarily found on NK cells. 24403531 1 47 theme unusual 268:274 arg1 it 254:255 it 254:255 it 254:255 Ly49B is a potentially important immunoregulator expressed on mouse myeloid cells, and it is thus an unusual member of the wider Ly49 family whose members are ordinarily found on NK cells. 24403531 4 48 dep affected 835:842 arg1 it 832:833 it 832:833 it 832:833 Binding was not significantly affected by inactivation of any of the four predicted N-linked glycosylation sites of Ly49B, nor was it affected by removal of the unique 20-aa C-terminal extension found in Ly49B. 24403531 2 49 theme substantial 371:381 arg1 divergence 392:401 substantial sequence divergence 371:401 substantial sequence divergence from other Ly49s 371:418 Ly49B displays substantial sequence divergence from other Ly49s and in particular shares virtually no amino acid sequence identity with the residues that have been reported to bind to MHC class I (cI) ligands in other Ly49s. 24403531 1 50 theme important 190:198 arg1 Ly49B 167:171 Ly49B 167:171 Ly49B 167:171 Ly49B is a potentially important immunoregulator expressed on mouse myeloid cells, and it is thus an unusual member of the wider Ly49 family whose members are ordinarily found on NK cells. 24403531 1 50 theme important 190:198 arg1 immunoregulator 200:214 a potentially important immunoregulator 176:214 a potentially important immunoregulator expressed on mouse myeloid cells 176:247 Ly49B is a potentially important immunoregulator expressed on mouse myeloid cells, and it is thus an unusual member of the wider Ly49 family whose members are ordinarily found on NK cells. 24403531 0 51 theme key 29:31 arg1 elements 44:51 key structural elements 29:51 key structural elements required for promiscuous binding to MHC class I molecules and new insights into the molecular evolution of Ly49s 29:164 Mutagenesis of Ly49B reveals key structural elements required for promiscuous binding to MHC class I molecules and new insights into the molecular evolution of Ly49s. 24403531 4 52 theme C-terminal 875:884 arg1 extension 886:894 the unique 20-aa C-terminal extension 858:894 the unique 20-aa C-terminal extension found in Ly49B 858:909 Binding was not significantly affected by inactivation of any of the four predicted N-linked glycosylation sites of Ly49B, nor was it affected by removal of the unique 20-aa C-terminal extension found in Ly49B. 24403531 2 53 dep displays 362:369 arg1 shares 438:443 shares 438:443 shares virtually no amino acid sequence identity with the residues that have been reported to bind to MHC class I (cI) ligands in other Ly49s 438:578 Ly49B displays substantial sequence divergence from other Ly49s and in particular shares virtually no amino acid sequence identity with the residues that have been reported to bind to MHC class I (cI) ligands in other Ly49s. 24403531 3 54 theme Ly49B 662:666 arg1 isoform 651:657 the BALB/c, but not the C57, isoform 622:657 the BALB/c, but not the C57, isoform of Ly49B 622:666 Despite this, we show in this study that the BALB/c, but not the C57, isoform of Ly49B displays promiscuous cI binding. 24403531 3 55 theme promiscuous 677:687 arg1 binding 692:698 promiscuous cI binding 677:698 promiscuous cI binding 677:698 Despite this, we show in this study that the BALB/c, but not the C57, isoform of Ly49B displays promiscuous cI binding. 24403531 0 56 theme molecular 137:145 arg1 evolution 147:155 the molecular evolution 133:155 the molecular evolution of Ly49s 133:164 Mutagenesis of Ly49B reveals key structural elements required for promiscuous binding to MHC class I molecules and new insights into the molecular evolution of Ly49s. 24403531 8 57 from 167 1452:1454 arg1 residues 1423:1430 C57 residues 1419:1430 C57 residues at positions 166 or 167 1419:1454 Remarkably, however, Ly49B(BALB) variants that have C57 residues at positions 166 or 167, and are unable to bind cI multimers, regain substantial cI binding when amino acid changes are made at distal positions, providing an explanation of how highly divergent Ly49s that retain the ability to bind cI molecules might have evolved. 24403531 8 58 theme cI 1665:1666 arg1 molecules 1668:1676 cI molecules 1665:1676 cI molecules 1665:1676 Remarkably, however, Ly49B(BALB) variants that have C57 residues at positions 166 or 167, and are unable to bind cI multimers, regain substantial cI binding when amino acid changes are made at distal positions, providing an explanation of how highly divergent Ly49s that retain the ability to bind cI molecules might have evolved. 24403531 6 59 theme Systematic 1168:1177 arg1 exchange 1179:1186 Systematic exchange 1168:1186 Systematic exchange of BALB/c and C57 residues 1168:1213 Systematic exchange of BALB/c and C57 residues revealed that Trp(166), Asn(167), and Cys(251) are of major importance for cI binding in Ly49B. 24403531 4 60 theme glycosylation 794:806 arg1 sites 808:812 the four predicted N-linked glycosylation sites 766:812 the four predicted N-linked glycosylation sites of Ly49B 766:821 Binding was not significantly affected by inactivation of any of the four predicted N-linked glycosylation sites of Ly49B, nor was it affected by removal of the unique 20-aa C-terminal extension found in Ly49B. 24403531 4 60 theme glycosylation 794:806 arg1 Ly49B 817:821 Ly49B 817:821 Ly49B 817:821 Binding was not significantly affected by inactivation of any of the four predicted N-linked glycosylation sites of Ly49B, nor was it affected by removal of the unique 20-aa C-terminal extension found in Ly49B. 24403531 4 61 theme N-linked 785:792 arg1 sites 808:812 the four predicted N-linked glycosylation sites 766:812 the four predicted N-linked glycosylation sites of Ly49B 766:821 Binding was not significantly affected by inactivation of any of the four predicted N-linked glycosylation sites of Ly49B, nor was it affected by removal of the unique 20-aa C-terminal extension found in Ly49B. 24403531 4 61 theme N-linked 785:792 arg1 Ly49B 817:821 Ly49B 817:821 Ly49B 817:821 Binding was not significantly affected by inactivation of any of the four predicted N-linked glycosylation sites of Ly49B, nor was it affected by removal of the unique 20-aa C-terminal extension found in Ly49B. 24403531 5 62 dep did 990:992 arg1 as 987:988 as 987:988 as 987:988 However, transfer of these C-terminal 20 aa to Ly49A inhibited cI binding, as did the addition of a hemagglutinin tag to the C terminus of Ly49B, demonstrating unexpectedly that the C-terminal region of Ly49s can play a significant role in ligand binding. 24403531 8 63 theme divergent 1617:1625 arg1 Ly49s 1627:1631 highly divergent Ly49s 1610:1631 highly divergent Ly49s that retain the ability to bind cI molecules 1610:1676 Remarkably, however, Ly49B(BALB) variants that have C57 residues at positions 166 or 167, and are unable to bind cI multimers, regain substantial cI binding when amino acid changes are made at distal positions, providing an explanation of how highly divergent Ly49s that retain the ability to bind cI molecules might have evolved. 24403531 1 64 theme wider 290:294 arg1 family 301:306 the wider Ly49 family 286:306 the wider Ly49 family whose members are ordinarily found on NK cells 286:353 Ly49B is a potentially important immunoregulator expressed on mouse myeloid cells, and it is thus an unusual member of the wider Ly49 family whose members are ordinarily found on NK cells. 24403531 8 65 theme Ly49B 1388:1392 arg1 variants 1400:1407 Ly49B(BALB) variants 1388:1407 Ly49B(BALB) variants 1388:1407 Remarkably, however, Ly49B(BALB) variants that have C57 residues at positions 166 or 167, and are unable to bind cI multimers, regain substantial cI binding when amino acid changes are made at distal positions, providing an explanation of how highly divergent Ly49s that retain the ability to bind cI molecules might have evolved. 24403531 8 66 theme substantial 1501:1511 arg1 binding 1516:1522 substantial cI binding 1501:1522 substantial cI binding 1501:1522 Remarkably, however, Ly49B(BALB) variants that have C57 residues at positions 166 or 167, and are unable to bind cI multimers, regain substantial cI binding when amino acid changes are made at distal positions, providing an explanation of how highly divergent Ly49s that retain the ability to bind cI molecules might have evolved. 24403531 6 67 theme major 1269:1273 arg1 importance 1275:1284 major importance 1269:1284 major importance 1269:1284 Systematic exchange of BALB/c and C57 residues revealed that Trp(166), Asn(167), and Cys(251) are of major importance for cI binding in Ly49B. 24403531 8 68 from positions 1435:1443 arg1 residues 1423:1430 C57 residues 1419:1430 C57 residues at positions 166 or 167 1419:1454 Remarkably, however, Ly49B(BALB) variants that have C57 residues at positions 166 or 167, and are unable to bind cI multimers, regain substantial cI binding when amino acid changes are made at distal positions, providing an explanation of how highly divergent Ly49s that retain the ability to bind cI molecules might have evolved. 24403531 8 69 theme cI 1513:1514 arg1 binding 1516:1522 substantial cI binding 1501:1522 substantial cI binding 1501:1522 Remarkably, however, Ly49B(BALB) variants that have C57 residues at positions 166 or 167, and are unable to bind cI multimers, regain substantial cI binding when amino acid changes are made at distal positions, providing an explanation of how highly divergent Ly49s that retain the ability to bind cI molecules might have evolved. 24403531 5 70 theme significant 1132:1142 arg1 role 1144:1147 a significant role 1130:1147 a significant role 1130:1147 However, transfer of these C-terminal 20 aa to Ly49A inhibited cI binding, as did the addition of a hemagglutinin tag to the C terminus of Ly49B, demonstrating unexpectedly that the C-terminal region of Ly49s can play a significant role in ligand binding. 24403531 2 71 theme sequence 469:476 arg1 identity 478:485 virtually no amino acid sequence identity 445:485 virtually no amino acid sequence identity 445:485 Ly49B displays substantial sequence divergence from other Ly49s and in particular shares virtually no amino acid sequence identity with the residues that have been reported to bind to MHC class I (cI) ligands in other Ly49s. 24403531 5 72 theme C-terminal 939:948 arg1 aa 953:954 these C-terminal 20 aa 933:954 these C-terminal 20 aa 933:954 However, transfer of these C-terminal 20 aa to Ly49A inhibited cI binding, as did the addition of a hemagglutinin tag to the C terminus of Ly49B, demonstrating unexpectedly that the C-terminal region of Ly49s can play a significant role in ligand binding. 24403531 7 73 theme Ly49 1354:1357 arg1 family 1359:1364 the Ly49 family 1350:1364 the Ly49 family 1350:1364 These residues are highly conserved in the Ly49 family. 24403531 1 74 theme mouse 229:233 arg1 cells 243:247 mouse myeloid cells 229:247 mouse myeloid cells 229:247 Ly49B is a potentially important immunoregulator expressed on mouse myeloid cells, and it is thus an unusual member of the wider Ly49 family whose members are ordinarily found on NK cells. 24403531 2 75 theme acid 464:467 arg1 identity 478:485 virtually no amino acid sequence identity 445:485 virtually no amino acid sequence identity 445:485 Ly49B displays substantial sequence divergence from other Ly49s and in particular shares virtually no amino acid sequence identity with the residues that have been reported to bind to MHC class I (cI) ligands in other Ly49s. 24403531 1 76 theme Ly49 296:299 arg1 family 301:306 the wider Ly49 family 286:306 the wider Ly49 family whose members are ordinarily found on NK cells 286:353 Ly49B is a potentially important immunoregulator expressed on mouse myeloid cells, and it is thus an unusual member of the wider Ly49 family whose members are ordinarily found on NK cells. 24403531 5 77 theme C-terminal 1094:1103 arg1 region 1105:1110 the C-terminal region 1090:1110 the C-terminal region of Ly49s 1090:1119 However, transfer of these C-terminal 20 aa to Ly49A inhibited cI binding, as did the addition of a hemagglutinin tag to the C terminus of Ly49B, demonstrating unexpectedly that the C-terminal region of Ly49s can play a significant role in ligand binding. 24403531 4 78 gly glycosylation 794:806 arg2 four 770:773 four 770:773 four 770:773 Binding was not significantly affected by inactivation of any of the four predicted N-linked glycosylation sites of Ly49B, nor was it affected by removal of the unique 20-aa C-terminal extension found in Ly49B. 24403531 4 78 gly glycosylation 794:806 arg2 Ly49B 817:821 Ly49B 817:821 Ly49B 817:821 Binding was not significantly affected by inactivation of any of the four predicted N-linked glycosylation sites of Ly49B, nor was it affected by removal of the unique 20-aa C-terminal extension found in Ly49B. 24403531 4 78 gly glycosylation 794:806 arg1 Ly49B 817:821 Ly49B 817:821 Ly49B 817:821 Binding was not significantly affected by inactivation of any of the four predicted N-linked glycosylation sites of Ly49B, nor was it affected by removal of the unique 20-aa C-terminal extension found in Ly49B. 24403531 4 78 gly glycosylation 794:806 arg2 sites 808:812 the four predicted N-linked glycosylation sites 766:812 the four predicted N-linked glycosylation sites of Ly49B 766:821 Binding was not significantly affected by inactivation of any of the four predicted N-linked glycosylation sites of Ly49B, nor was it affected by removal of the unique 20-aa C-terminal extension found in Ly49B. 24403531 8 79 theme cI 1480:1481 arg1 multimers 1483:1491 cI multimers 1480:1491 cI multimers 1480:1491 Remarkably, however, Ly49B(BALB) variants that have C57 residues at positions 166 or 167, and are unable to bind cI multimers, regain substantial cI binding when amino acid changes are made at distal positions, providing an explanation of how highly divergent Ly49s that retain the ability to bind cI molecules might have evolved. 24403531 1 80 theme myeloid 235:241 arg1 cells 243:247 mouse myeloid cells 229:247 mouse myeloid cells 229:247 Ly49B is a potentially important immunoregulator expressed on mouse myeloid cells, and it is thus an unusual member of the wider Ly49 family whose members are ordinarily found on NK cells. 24760753 10 0 from position 1460:1467 arg1 Ser 1453:1455 Ser 1453:1455 Ser at position -1 1453:1470 Altogether, these findings suggested that a substrate (peptide or protein) with Pro, Ala at position -2, and/or Val, Ala, Thr, Ser at position -1, and/or Ala, Ser, Pro, Thr, Gly at position +2 would have more chances for O-GlcNAcylation. 24760753 10 1 from position 1507:1514 arg1 Pro 1406:1408 Pro 1406:1408 Pro 1406:1408 Altogether, these findings suggested that a substrate (peptide or protein) with Pro, Ala at position -2, and/or Val, Ala, Thr, Ser at position -1, and/or Ala, Ser, Pro, Thr, Gly at position +2 would have more chances for O-GlcNAcylation. 24760753 5 2 dep site 678:681 arg1 position 696:703 position 0 696:705 position 0 696:705 Frequency analysis on many O-GlcNAcylated peptides revealed a signature sequence, PPVS/TSATT, around the modification site (underlined, position 0). 24760753 9 3 theme Pro 1208:1210 arg1 acids 1197:1201 The preferred amino acids 1177:1201 The preferred amino acids 1177:1201 The preferred amino acids were Pro > Ala > Gly at position -2, Ala > Thr > Val > Lys > Pro at position -1, and Ala > Gly > Arg > Glu at position +2. 24760753 9 3 theme Pro 1208:1210 arg1 Gly 1220:1222 Pro > Ala > Gly 1208:1222 Pro > Ala > Gly at position -2 1208:1237 The preferred amino acids were Pro > Ala > Gly at position -2, Ala > Thr > Val > Lys > Pro at position -1, and Ala > Gly > Arg > Glu at position +2. 24760753 13 4 theme functional 1850:1859 arg1 studies 1861:1867 further functional studies 1842:1867 further functional studies 1842:1867 The result will contribute to predicting the O-GlcNAc status of a protein and further functional studies. 24760753 4 5 theme many 453:456 arg1 sites 474:478 many O-GlcNAcylation sites 453:478 many O-GlcNAcylation sites 453:478 Structural analysis of many O-GlcNAcylation sites indicated that the modification occurred predominantly in a random coil region. 24760753 9 6 theme Ala 1214:1216 arg1 acids 1197:1201 The preferred amino acids 1177:1201 The preferred amino acids 1177:1201 The preferred amino acids were Pro > Ala > Gly at position -2, Ala > Thr > Val > Lys > Pro at position -1, and Ala > Gly > Arg > Glu at position +2. 24760753 9 6 theme Ala 1214:1216 arg1 Gly 1220:1222 Pro > Ala > Gly 1208:1222 Pro > Ala > Gly at position -2 1208:1237 The preferred amino acids were Pro > Ala > Gly at position -2, Ala > Thr > Val > Lys > Pro at position -1, and Ala > Gly > Arg > Glu at position +2. 24760753 4 7 theme sites 474:478 arg1 analysis 441:448 Structural analysis 430:448 Structural analysis of many O-GlcNAcylation sites 430:478 Structural analysis of many O-GlcNAcylation sites indicated that the modification occurred predominantly in a random coil region. 24760753 5 8 theme many 582:585 arg1 peptides 602:609 many O-GlcNAcylated peptides 582:609 many O-GlcNAcylated peptides 582:609 Frequency analysis on many O-GlcNAcylated peptides revealed a signature sequence, PPVS/TSATT, around the modification site (underlined, position 0). 24760753 6 9 theme preference 849:858 arg1 O-GlcNAcylation 800:814 O-GlcNAcylation 800:814 O-GlcNAcylation of peptides and their amino acid preference 800:858 Based on the sequence, a peptide panel was designed to investigate key positions affecting O-GlcNAcylation of peptides and their amino acid preference. 24760753 1 10 theme physiological 223:235 arg1 processes 237:245 various physiological processes 215:245 various physiological processes 215:245 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is widely distributed on nucleocytoplasmic proteins and participates in various physiological processes. 24760753 11 11 from sites 1600:1604 arg1 sOGT 1609:1612 sOGT 1609:1612 sOGT (S52 and T449) 1609:1627 To test the rule, 2 O-GlcNAcylation sites on sOGT (S52 and T449) were predicted and confirmed by Western blot. 24760753 9 12 theme > 1244:1244 arg1 Val 1252:1254 Ala > Thr > Val 1240:1254 Ala > Thr > Val > Lys > Pro at position -1 1240:1281 The preferred amino acids were Pro > Ala > Gly at position -2, Ala > Thr > Val > Lys > Pro at position -1, and Ala > Gly > Arg > Glu at position +2. 24760753 2 13 theme numerous 271:278 arg1 proteins 280:287 numerous proteins 271:287 numerous proteins 271:287 But O-GlcNAc status on numerous proteins remains unknown. 24760753 7 14 theme high 1037:1040 arg1 reactivity 1042:1051 high reactivity 1037:1051 high reactivity 1037:1051 It was indicated that 3 positions (-2, -1, and +2) had an important role for this modification, where the presence of uncharged amino acids with small side chains could confer high reactivity. 24760753 9 15 from position 1227:1234 arg1 Val 1252:1254 Ala > Thr > Val 1240:1254 Ala > Thr > Val > Lys > Pro at position -1 1240:1281 The preferred amino acids were Pro > Ala > Gly at position -2, Ala > Thr > Val > Lys > Pro at position -1, and Ala > Gly > Arg > Glu at position +2. 24760753 9 15 from position 1227:1234 arg1 Arg 1300:1302 Ala > Gly > Arg 1288:1302 Ala > Gly > Arg 1288:1302 The preferred amino acids were Pro > Ala > Gly at position -2, Ala > Thr > Val > Lys > Pro at position -1, and Ala > Gly > Arg > Glu at position +2. 24760753 9 15 from position 1227:1234 arg1 acids 1197:1201 The preferred amino acids 1177:1201 The preferred amino acids 1177:1201 The preferred amino acids were Pro > Ala > Gly at position -2, Ala > Thr > Val > Lys > Pro at position -1, and Ala > Gly > Arg > Glu at position +2. 24760753 9 15 from position 1227:1234 arg1 Gly 1220:1222 Pro > Ala > Gly 1208:1222 Pro > Ala > Gly at position -2 1208:1237 The preferred amino acids were Pro > Ala > Gly at position -2, Ala > Thr > Val > Lys > Pro at position -1, and Ala > Gly > Arg > Glu at position +2. 24760753 9 16 theme > 1250:1250 arg1 Val 1252:1254 Ala > Thr > Val 1240:1254 Ala > Thr > Val > Lys > Pro at position -1 1240:1281 The preferred amino acids were Pro > Ala > Gly at position -2, Ala > Thr > Val > Lys > Pro at position -1, and Ala > Gly > Arg > Glu at position +2. 24760753 7 17 with acids 995:999 arg1 chains 1017:1022 small side chains 1006:1022 small side chains 1006:1022 It was indicated that 3 positions (-2, -1, and +2) had an important role for this modification, where the presence of uncharged amino acids with small side chains could confer high reactivity. 24760753 9 18 theme > 1256:1256 arg1 Pro 1264:1266 > Lys > Pro 1256:1266 Ala > Thr > Val > Lys > Pro at position -1 1240:1281 The preferred amino acids were Pro > Ala > Gly at position -2, Ala > Thr > Val > Lys > Pro at position -1, and Ala > Gly > Arg > Glu at position +2. 24760753 7 19 theme side 1012:1015 arg1 chains 1017:1022 small side chains 1006:1022 small side chains 1006:1022 It was indicated that 3 positions (-2, -1, and +2) had an important role for this modification, where the presence of uncharged amino acids with small side chains could confer high reactivity. 24760753 11 20 dep sOGT 1609:1612 arg1 S52 1615:1617 S52 1615:1617 S52 1615:1617 To test the rule, 2 O-GlcNAcylation sites on sOGT (S52 and T449) were predicted and confirmed by Western blot. 24760753 11 20 dep sOGT 1609:1612 arg1 T449 1623:1626 T449 1623:1626 T449 1623:1626 To test the rule, 2 O-GlcNAcylation sites on sOGT (S52 and T449) were predicted and confirmed by Western blot. 24760753 1 21 theme nucleocytoplasmic 168:184 arg1 proteins 186:193 nucleocytoplasmic proteins 168:193 nucleocytoplasmic proteins 168:193 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is widely distributed on nucleocytoplasmic proteins and participates in various physiological processes. 24760753 7 22 contain had 912:914 arg1 positions 885:893 3 positions 883:893 3 positions (-2, -1, and +2) 883:910 It was indicated that 3 positions (-2, -1, and +2) had an important role for this modification, where the presence of uncharged amino acids with small side chains could confer high reactivity. 24760753 7 22 contain had 912:914 arg2 role 929:932 an important role 916:932 an important role 916:932 It was indicated that 3 positions (-2, -1, and +2) had an important role for this modification, where the presence of uncharged amino acids with small side chains could confer high reactivity. 24760753 0 23 theme transferase 75:85 arg1 specificity 51:61 the acceptor specificity 38:61 the acceptor specificity of O-GlcNAc transferase 38:85 A peptide panel investigation reveals the acceptor specificity of O-GlcNAc transferase. 24760753 9 24 from position 1313:1320 arg1 Val 1252:1254 Ala > Thr > Val 1240:1254 Ala > Thr > Val > Lys > Pro at position -1 1240:1281 The preferred amino acids were Pro > Ala > Gly at position -2, Ala > Thr > Val > Lys > Pro at position -1, and Ala > Gly > Arg > Glu at position +2. 24760753 9 24 from position 1313:1320 arg1 Arg 1300:1302 Ala > Gly > Arg 1288:1302 Ala > Gly > Arg 1288:1302 The preferred amino acids were Pro > Ala > Gly at position -2, Ala > Thr > Val > Lys > Pro at position -1, and Ala > Gly > Arg > Glu at position +2. 24760753 9 24 from position 1313:1320 arg1 acids 1197:1201 The preferred amino acids 1177:1201 The preferred amino acids 1177:1201 The preferred amino acids were Pro > Ala > Gly at position -2, Ala > Thr > Val > Lys > Pro at position -1, and Ala > Gly > Arg > Glu at position +2. 24760753 9 24 from position 1313:1320 arg1 Gly 1220:1222 Pro > Ala > Gly 1208:1222 Pro > Ala > Gly at position -2 1208:1237 The preferred amino acids were Pro > Ala > Gly at position -2, Ala > Thr > Val > Lys > Pro at position -1, and Ala > Gly > Arg > Glu at position +2. 24760753 7 25 theme amino 989:993 arg1 acids 995:999 uncharged amino acids 979:999 uncharged amino acids with small side chains 979:1022 It was indicated that 3 positions (-2, -1, and +2) had an important role for this modification, where the presence of uncharged amino acids with small side chains could confer high reactivity. 24760753 9 26 dep Gly 1220:1222 arg1 Glu 1306:1308 > Glu 1304:1308 > Glu 1304:1308 The preferred amino acids were Pro > Ala > Gly at position -2, Ala > Thr > Val > Lys > Pro at position -1, and Ala > Gly > Arg > Glu at position +2. 24760753 10 27 from position 1418:1425 arg1 Ala 1411:1413 Ala 1411:1413 Ala at position -2 1411:1428 Altogether, these findings suggested that a substrate (peptide or protein) with Pro, Ala at position -2, and/or Val, Ala, Thr, Ser at position -1, and/or Ala, Ser, Pro, Thr, Gly at position +2 would have more chances for O-GlcNAcylation. 24760753 13 28 theme studies 1861:1867 arg1 status 1818:1823 the O-GlcNAc status 1805:1823 the O-GlcNAc status of a protein and further functional studies 1805:1867 The result will contribute to predicting the O-GlcNAc status of a protein and further functional studies. 24760753 8 29 theme amino 1058:1062 arg1 preference 1069:1078 The amino acid preference 1054:1078 The amino acid preference at key positions 1054:1095 The amino acid preference at key positions was further investigated on bovine crystalline α via site-directed mutagenesis. 24760753 10 30 with substrate 1370:1378 arg1 Pro 1490:1492 Pro 1490:1492 Pro 1490:1492 Altogether, these findings suggested that a substrate (peptide or protein) with Pro, Ala at position -2, and/or Val, Ala, Thr, Ser at position -1, and/or Ala, Ser, Pro, Thr, Gly at position +2 would have more chances for O-GlcNAcylation. 24760753 10 30 with substrate 1370:1378 arg1 Thr 1448:1450 Thr 1448:1450 Thr 1448:1450 Altogether, these findings suggested that a substrate (peptide or protein) with Pro, Ala at position -2, and/or Val, Ala, Thr, Ser at position -1, and/or Ala, Ser, Pro, Thr, Gly at position +2 would have more chances for O-GlcNAcylation. 24760753 10 30 with substrate 1370:1378 arg1 Thr 1495:1497 Thr 1495:1497 Thr 1495:1497 Altogether, these findings suggested that a substrate (peptide or protein) with Pro, Ala at position -2, and/or Val, Ala, Thr, Ser at position -1, and/or Ala, Ser, Pro, Thr, Gly at position +2 would have more chances for O-GlcNAcylation. 24760753 10 30 with substrate 1370:1378 arg1 Pro 1406:1408 Pro 1406:1408 Pro 1406:1408 Altogether, these findings suggested that a substrate (peptide or protein) with Pro, Ala at position -2, and/or Val, Ala, Thr, Ser at position -1, and/or Ala, Ser, Pro, Thr, Gly at position +2 would have more chances for O-GlcNAcylation. 24760753 10 30 with substrate 1370:1378 arg1 Ser 1453:1455 Ser 1453:1455 Ser at position -1 1453:1470 Altogether, these findings suggested that a substrate (peptide or protein) with Pro, Ala at position -2, and/or Val, Ala, Thr, Ser at position -1, and/or Ala, Ser, Pro, Thr, Gly at position +2 would have more chances for O-GlcNAcylation. 24760753 10 30 with substrate 1370:1378 arg1 Ala 1480:1482 Ala 1480:1482 Ala 1480:1482 Altogether, these findings suggested that a substrate (peptide or protein) with Pro, Ala at position -2, and/or Val, Ala, Thr, Ser at position -1, and/or Ala, Ser, Pro, Thr, Gly at position +2 would have more chances for O-GlcNAcylation. 24760753 10 30 with substrate 1370:1378 arg1 Ala 1411:1413 Ala 1411:1413 Ala at position -2 1411:1428 Altogether, these findings suggested that a substrate (peptide or protein) with Pro, Ala at position -2, and/or Val, Ala, Thr, Ser at position -1, and/or Ala, Ser, Pro, Thr, Gly at position +2 would have more chances for O-GlcNAcylation. 24760753 10 30 with substrate 1370:1378 arg1 Val 1438:1440 Val 1438:1440 Val 1438:1440 Altogether, these findings suggested that a substrate (peptide or protein) with Pro, Ala at position -2, and/or Val, Ala, Thr, Ser at position -1, and/or Ala, Ser, Pro, Thr, Gly at position +2 would have more chances for O-GlcNAcylation. 24760753 10 30 with substrate 1370:1378 arg1 Ser 1485:1487 Ser 1485:1487 Ser 1485:1487 Altogether, these findings suggested that a substrate (peptide or protein) with Pro, Ala at position -2, and/or Val, Ala, Thr, Ser at position -1, and/or Ala, Ser, Pro, Thr, Gly at position +2 would have more chances for O-GlcNAcylation. 24760753 10 30 with substrate 1370:1378 arg1 Gly 1500:1502 Gly 1500:1502 Gly 1500:1502 Altogether, these findings suggested that a substrate (peptide or protein) with Pro, Ala at position -2, and/or Val, Ala, Thr, Ser at position -1, and/or Ala, Ser, Pro, Thr, Gly at position +2 would have more chances for O-GlcNAcylation. 24760753 10 30 with substrate 1370:1378 arg1 Ala 1443:1445 Ala 1443:1445 Ala 1443:1445 Altogether, these findings suggested that a substrate (peptide or protein) with Pro, Ala at position -2, and/or Val, Ala, Thr, Ser at position -1, and/or Ala, Ser, Pro, Thr, Gly at position +2 would have more chances for O-GlcNAcylation. 24760753 4 31 theme coil 547:550 arg1 region 552:557 a random coil region 538:557 a random coil region 538:557 Structural analysis of many O-GlcNAcylation sites indicated that the modification occurred predominantly in a random coil region. 24760753 13 32 theme O-GlcNAc 1809:1816 arg1 status 1818:1823 the O-GlcNAc status 1805:1823 the O-GlcNAc status of a protein and further functional studies 1805:1867 The result will contribute to predicting the O-GlcNAc status of a protein and further functional studies. 24760753 9 33 theme > 1292:1292 arg1 Arg 1300:1302 Ala > Gly > Arg 1288:1302 Ala > Gly > Arg 1288:1302 The preferred amino acids were Pro > Ala > Gly at position -2, Ala > Thr > Val > Lys > Pro at position -1, and Ala > Gly > Arg > Glu at position +2. 24760753 8 34 theme key 1083:1085 arg1 positions 1087:1095 key positions 1083:1095 key positions 1083:1095 The amino acid preference at key positions was further investigated on bovine crystalline α via site-directed mutagenesis. 24760753 5 35 theme modification 665:676 arg1 site 678:681 the modification site 661:681 the modification site (underlined, position 0) 661:706 Frequency analysis on many O-GlcNAcylated peptides revealed a signature sequence, PPVS/TSATT, around the modification site (underlined, position 0). 24760753 0 36 theme panel 10:14 arg1 investigation 16:28 A peptide panel investigation 0:28 A peptide panel investigation 0:28 A peptide panel investigation reveals the acceptor specificity of O-GlcNAc transferase. 24760753 9 37 theme > 1298:1298 arg1 Arg 1300:1302 Ala > Gly > Arg 1288:1302 Ala > Gly > Arg 1288:1302 The preferred amino acids were Pro > Ala > Gly at position -2, Ala > Thr > Val > Lys > Pro at position -1, and Ala > Gly > Arg > Glu at position +2. 24760753 9 38 theme > 1304:1304 arg1 Glu 1306:1308 > Glu 1304:1308 > Glu 1304:1308 The preferred amino acids were Pro > Ala > Gly at position -2, Ala > Thr > Val > Lys > Pro at position -1, and Ala > Gly > Arg > Glu at position +2. 24760753 0 39 theme acceptor 42:49 arg1 specificity 51:61 the acceptor specificity 38:61 the acceptor specificity of O-GlcNAc transferase 38:85 A peptide panel investigation reveals the acceptor specificity of O-GlcNAc transferase. 24760753 8 40 theme bovine 1125:1130 arg1 α 1144:1144 bovine crystalline α 1125:1144 bovine crystalline α 1125:1144 The amino acid preference at key positions was further investigated on bovine crystalline α via site-directed mutagenesis. 24760753 6 41 theme peptides 819:826 arg1 O-GlcNAcylation 800:814 O-GlcNAcylation 800:814 O-GlcNAcylation of peptides and their amino acid preference 800:858 Based on the sequence, a peptide panel was designed to investigate key positions affecting O-GlcNAcylation of peptides and their amino acid preference. 24760753 13 42 theme protein 1830:1836 arg1 status 1818:1823 the O-GlcNAc status 1805:1823 the O-GlcNAc status of a protein and further functional studies 1805:1867 The result will contribute to predicting the O-GlcNAc status of a protein and further functional studies. 24760753 9 43 theme amino 1191:1195 arg1 acids 1197:1201 The preferred amino acids 1177:1201 The preferred amino acids 1177:1201 The preferred amino acids were Pro > Ala > Gly at position -2, Ala > Thr > Val > Lys > Pro at position -1, and Ala > Gly > Arg > Glu at position +2. 24760753 9 43 theme amino 1191:1195 arg1 Gly 1220:1222 Pro > Ala > Gly 1208:1222 Pro > Ala > Gly at position -2 1208:1237 The preferred amino acids were Pro > Ala > Gly at position -2, Ala > Thr > Val > Lys > Pro at position -1, and Ala > Gly > Arg > Glu at position +2. 24760753 8 44 theme site-directed 1150:1162 arg1 mutagenesis 1164:1174 site-directed mutagenesis 1150:1174 site-directed mutagenesis 1150:1174 The amino acid preference at key positions was further investigated on bovine crystalline α via site-directed mutagenesis. 24760753 1 45 link O-linked 88:95 arg1 β-N-acetylglucosaminylation 97:123 O-linked β-N-acetylglucosaminylation 88:123 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) 88:141 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is widely distributed on nucleocytoplasmic proteins and participates in various physiological processes. 24760753 1 45 link O-linked 88:95 arg1 O-GlcNAcylation 126:140 O-GlcNAcylation 126:140 O-GlcNAcylation 126:140 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is widely distributed on nucleocytoplasmic proteins and participates in various physiological processes. 24760753 7 46 theme important 919:927 arg1 role 929:932 an important role 916:932 an important role 916:932 It was indicated that 3 positions (-2, -1, and +2) had an important role for this modification, where the presence of uncharged amino acids with small side chains could confer high reactivity. 24760753 4 47 theme O-GlcNAcylation 458:472 arg1 sites 474:478 many O-GlcNAcylation sites 453:478 many O-GlcNAcylation sites 453:478 Structural analysis of many O-GlcNAcylation sites indicated that the modification occurred predominantly in a random coil region. 24760753 9 48 theme > 1212:1212 arg1 acids 1197:1201 The preferred amino acids 1177:1201 The preferred amino acids 1177:1201 The preferred amino acids were Pro > Ala > Gly at position -2, Ala > Thr > Val > Lys > Pro at position -1, and Ala > Gly > Arg > Glu at position +2. 24760753 9 48 theme > 1212:1212 arg1 Gly 1220:1222 Pro > Ala > Gly 1208:1222 Pro > Ala > Gly at position -2 1208:1237 The preferred amino acids were Pro > Ala > Gly at position -2, Ala > Thr > Val > Lys > Pro at position -1, and Ala > Gly > Arg > Glu at position +2. 24760753 7 49 theme small 1006:1010 arg1 chains 1017:1022 small side chains 1006:1022 small side chains 1006:1022 It was indicated that 3 positions (-2, -1, and +2) had an important role for this modification, where the presence of uncharged amino acids with small side chains could confer high reactivity. 24760753 9 50 dep Val 1252:1254 arg1 Pro 1264:1266 > Lys > Pro 1256:1266 Ala > Thr > Val > Lys > Pro at position -1 1240:1281 The preferred amino acids were Pro > Ala > Gly at position -2, Ala > Thr > Val > Lys > Pro at position -1, and Ala > Gly > Arg > Glu at position +2. 24760753 9 51 theme > 1218:1218 arg1 acids 1197:1201 The preferred amino acids 1177:1201 The preferred amino acids 1177:1201 The preferred amino acids were Pro > Ala > Gly at position -2, Ala > Thr > Val > Lys > Pro at position -1, and Ala > Gly > Arg > Glu at position +2. 24760753 9 51 theme > 1218:1218 arg1 Gly 1220:1222 Pro > Ala > Gly 1208:1222 Pro > Ala > Gly at position -2 1208:1237 The preferred amino acids were Pro > Ala > Gly at position -2, Ala > Thr > Val > Lys > Pro at position -1, and Ala > Gly > Arg > Glu at position +2. 24760753 4 52 theme Structural 430:439 arg1 analysis 441:448 Structural analysis 430:448 Structural analysis of many O-GlcNAcylation sites 430:478 Structural analysis of many O-GlcNAcylation sites indicated that the modification occurred predominantly in a random coil region. 24760753 5 53 theme O-GlcNAcylated 587:600 arg1 peptides 602:609 many O-GlcNAcylated peptides 582:609 many O-GlcNAcylated peptides 582:609 Frequency analysis on many O-GlcNAcylated peptides revealed a signature sequence, PPVS/TSATT, around the modification site (underlined, position 0). 24760753 1 54 theme various 215:221 arg1 processes 237:245 various physiological processes 215:245 various physiological processes 215:245 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is widely distributed on nucleocytoplasmic proteins and participates in various physiological processes. 24760753 12 55 theme sequence 1724:1731 arg1 signature 1733:1741 the sequence signature 1720:1741 the sequence signature for O-GlcNAcylation 1720:1761 The present work systematically investigated the sequence signature for O-GlcNAcylation. 24760753 6 56 theme acid 844:847 arg1 preference 849:858 their amino acid preference 832:858 their amino acid preference 832:858 Based on the sequence, a peptide panel was designed to investigate key positions affecting O-GlcNAcylation of peptides and their amino acid preference. 24760753 10 57 contain have 1525:1528 arg2 chances 1535:1541 more chances 1530:1541 more chances for O-GlcNAcylation 1530:1561 Altogether, these findings suggested that a substrate (peptide or protein) with Pro, Ala at position -2, and/or Val, Ala, Thr, Ser at position -1, and/or Ala, Ser, Pro, Thr, Gly at position +2 would have more chances for O-GlcNAcylation. 24760753 10 57 contain have 1525:1528 arg1 substrate 1370:1378 a substrate 1368:1378 a substrate (peptide or protein) with Pro, Ala at position -2, and/or Val, Ala, Thr, Ser at position -1, and/or Ala, Ser, Pro, Thr, Gly at position +2 1368:1517 Altogether, these findings suggested that a substrate (peptide or protein) with Pro, Ala at position -2, and/or Val, Ala, Thr, Ser at position -1, and/or Ala, Ser, Pro, Thr, Gly at position +2 would have more chances for O-GlcNAcylation. 24760753 10 58 theme more 1530:1533 arg1 chances 1535:1541 more chances 1530:1541 more chances for O-GlcNAcylation 1530:1561 Altogether, these findings suggested that a substrate (peptide or protein) with Pro, Ala at position -2, and/or Val, Ala, Thr, Ser at position -1, and/or Ala, Ser, Pro, Thr, Gly at position +2 would have more chances for O-GlcNAcylation. 24760753 9 59 theme Ala 1240:1242 arg1 Val 1252:1254 Ala > Thr > Val 1240:1254 Ala > Thr > Val > Lys > Pro at position -1 1240:1281 The preferred amino acids were Pro > Ala > Gly at position -2, Ala > Thr > Val > Lys > Pro at position -1, and Ala > Gly > Arg > Glu at position +2. 24760753 5 60 theme Frequency 560:568 arg1 analysis 570:577 Frequency analysis 560:577 Frequency analysis on many O-GlcNAcylated peptides 560:609 Frequency analysis on many O-GlcNAcylated peptides revealed a signature sequence, PPVS/TSATT, around the modification site (underlined, position 0). 24760753 9 61 from position 1271:1278 arg1 Val 1252:1254 Ala > Thr > Val 1240:1254 Ala > Thr > Val > Lys > Pro at position -1 1240:1281 The preferred amino acids were Pro > Ala > Gly at position -2, Ala > Thr > Val > Lys > Pro at position -1, and Ala > Gly > Arg > Glu at position +2. 24760753 9 61 from position 1271:1278 arg1 Arg 1300:1302 Ala > Gly > Arg 1288:1302 Ala > Gly > Arg 1288:1302 The preferred amino acids were Pro > Ala > Gly at position -2, Ala > Thr > Val > Lys > Pro at position -1, and Ala > Gly > Arg > Glu at position +2. 24760753 9 61 from position 1271:1278 arg1 acids 1197:1201 The preferred amino acids 1177:1201 The preferred amino acids 1177:1201 The preferred amino acids were Pro > Ala > Gly at position -2, Ala > Thr > Val > Lys > Pro at position -1, and Ala > Gly > Arg > Glu at position +2. 24760753 9 61 from position 1271:1278 arg1 Gly 1220:1222 Pro > Ala > Gly 1208:1222 Pro > Ala > Gly at position -2 1208:1237 The preferred amino acids were Pro > Ala > Gly at position -2, Ala > Thr > Val > Lys > Pro at position -1, and Ala > Gly > Arg > Glu at position +2. 24760753 8 62 from positions 1087:1095 arg1 preference 1069:1078 The amino acid preference 1054:1078 The amino acid preference at key positions 1054:1095 The amino acid preference at key positions was further investigated on bovine crystalline α via site-directed mutagenesis. 24760753 4 63 theme random 540:545 arg1 region 552:557 a random coil region 538:557 a random coil region 538:557 Structural analysis of many O-GlcNAcylation sites indicated that the modification occurred predominantly in a random coil region. 24760753 9 64 theme Thr 1246:1248 arg1 Val 1252:1254 Ala > Thr > Val 1240:1254 Ala > Thr > Val > Lys > Pro at position -1 1240:1281 The preferred amino acids were Pro > Ala > Gly at position -2, Ala > Thr > Val > Lys > Pro at position -1, and Ala > Gly > Arg > Glu at position +2. 24760753 5 65 theme underlined 684:693 arg1 position 696:703 position 0 696:705 position 0 696:705 Frequency analysis on many O-GlcNAcylated peptides revealed a signature sequence, PPVS/TSATT, around the modification site (underlined, position 0). 24760753 3 66 theme computational 346:358 arg1 analysis 360:367 computational analysis 346:367 computational analysis combined with experimental study 346:400 To better understand this modification, computational analysis combined with experimental study was performed in this work. 24760753 0 67 theme O-GlcNAc 66:73 arg1 transferase 75:85 O-GlcNAc transferase 66:85 O-GlcNAc transferase 66:85 A peptide panel investigation reveals the acceptor specificity of O-GlcNAc transferase. 24760753 9 68 theme Lys 1258:1260 arg1 Pro 1264:1266 > Lys > Pro 1256:1266 Ala > Thr > Val > Lys > Pro at position -1 1240:1281 The preferred amino acids were Pro > Ala > Gly at position -2, Ala > Thr > Val > Lys > Pro at position -1, and Ala > Gly > Arg > Glu at position +2. 24760753 5 69 theme signature 622:630 arg1 PPVS/TSATT 642:651 PPVS/TSATT 642:651 PPVS/TSATT 642:651 Frequency analysis on many O-GlcNAcylated peptides revealed a signature sequence, PPVS/TSATT, around the modification site (underlined, position 0). 24760753 5 69 theme signature 622:630 arg1 sequence 632:639 a signature sequence 620:639 a signature sequence 620:639 Frequency analysis on many O-GlcNAcylated peptides revealed a signature sequence, PPVS/TSATT, around the modification site (underlined, position 0). 24760753 3 70 theme experimental 383:394 arg1 study 396:400 experimental study 383:400 experimental study 383:400 To better understand this modification, computational analysis combined with experimental study was performed in this work. 24760753 8 71 theme acid 1064:1067 arg1 preference 1069:1078 The amino acid preference 1054:1078 The amino acid preference at key positions 1054:1095 The amino acid preference at key positions was further investigated on bovine crystalline α via site-directed mutagenesis. 24760753 7 72 theme acids 995:999 arg1 presence 967:974 the presence 963:974 the presence of uncharged amino acids with small side chains 963:1022 It was indicated that 3 positions (-2, -1, and +2) had an important role for this modification, where the presence of uncharged amino acids with small side chains could confer high reactivity. 24760753 9 73 theme preferred 1181:1189 arg1 acids 1197:1201 The preferred amino acids 1177:1201 The preferred amino acids 1177:1201 The preferred amino acids were Pro > Ala > Gly at position -2, Ala > Thr > Val > Lys > Pro at position -1, and Ala > Gly > Arg > Glu at position +2. 24760753 9 73 theme preferred 1181:1189 arg1 Gly 1220:1222 Pro > Ala > Gly 1208:1222 Pro > Ala > Gly at position -2 1208:1237 The preferred amino acids were Pro > Ala > Gly at position -2, Ala > Thr > Val > Lys > Pro at position -1, and Ala > Gly > Arg > Glu at position +2. 24760753 6 74 theme key 776:778 arg1 positions 780:788 key positions 776:788 key positions affecting O-GlcNAcylation of peptides and their amino acid preference 776:858 Based on the sequence, a peptide panel was designed to investigate key positions affecting O-GlcNAcylation of peptides and their amino acid preference. 24760753 11 75 theme O-GlcNAcylation 1584:1598 arg1 sites 1600:1604 2 O-GlcNAcylation sites 1582:1604 2 O-GlcNAcylation sites on sOGT (S52 and T449) 1582:1627 To test the rule, 2 O-GlcNAcylation sites on sOGT (S52 and T449) were predicted and confirmed by Western blot. 24760753 7 76 theme uncharged 979:987 arg1 acids 995:999 uncharged amino acids 979:999 uncharged amino acids with small side chains 979:1022 It was indicated that 3 positions (-2, -1, and +2) had an important role for this modification, where the presence of uncharged amino acids with small side chains could confer high reactivity. 24760753 2 77 from status 261:266 arg1 proteins 280:287 numerous proteins 271:287 numerous proteins 271:287 But O-GlcNAc status on numerous proteins remains unknown. 24760753 0 78 theme peptide 2:8 arg1 investigation 16:28 A peptide panel investigation 0:28 A peptide panel investigation 0:28 A peptide panel investigation reveals the acceptor specificity of O-GlcNAc transferase. 24760753 9 79 theme Ala 1288:1290 arg1 Arg 1300:1302 Ala > Gly > Arg 1288:1302 Ala > Gly > Arg 1288:1302 The preferred amino acids were Pro > Ala > Gly at position -2, Ala > Thr > Val > Lys > Pro at position -1, and Ala > Gly > Arg > Glu at position +2. 24760753 1 80 theme O-linked 88:95 arg1 β-N-acetylglucosaminylation 97:123 O-linked β-N-acetylglucosaminylation 88:123 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) 88:141 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is widely distributed on nucleocytoplasmic proteins and participates in various physiological processes. 24760753 1 80 theme O-linked 88:95 arg1 O-GlcNAcylation 126:140 O-GlcNAcylation 126:140 O-GlcNAcylation 126:140 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is widely distributed on nucleocytoplasmic proteins and participates in various physiological processes. 24760753 9 81 theme Gly 1294:1296 arg1 Arg 1300:1302 Ala > Gly > Arg 1288:1302 Ala > Gly > Arg 1288:1302 The preferred amino acids were Pro > Ala > Gly at position -2, Ala > Thr > Val > Lys > Pro at position -1, and Ala > Gly > Arg > Glu at position +2. 24760753 6 82 theme peptide 734:740 arg1 panel 742:746 a peptide panel 732:746 a peptide panel 732:746 Based on the sequence, a peptide panel was designed to investigate key positions affecting O-GlcNAcylation of peptides and their amino acid preference. 24760753 9 83 theme > 1262:1262 arg1 Pro 1264:1266 > Lys > Pro 1256:1266 Ala > Thr > Val > Lys > Pro at position -1 1240:1281 The preferred amino acids were Pro > Ala > Gly at position -2, Ala > Thr > Val > Lys > Pro at position -1, and Ala > Gly > Arg > Glu at position +2. 24760753 10 84 dep substrate 1370:1378 arg1 protein 1392:1398 protein 1392:1398 protein 1392:1398 Altogether, these findings suggested that a substrate (peptide or protein) with Pro, Ala at position -2, and/or Val, Ala, Thr, Ser at position -1, and/or Ala, Ser, Pro, Thr, Gly at position +2 would have more chances for O-GlcNAcylation. 24760753 10 84 dep substrate 1370:1378 arg1 peptide 1381:1387 peptide 1381:1387 peptide 1381:1387 Altogether, these findings suggested that a substrate (peptide or protein) with Pro, Ala at position -2, and/or Val, Ala, Thr, Ser at position -1, and/or Ala, Ser, Pro, Thr, Gly at position +2 would have more chances for O-GlcNAcylation. 24760753 12 85 theme present 1679:1685 arg1 work 1687:1690 The present work 1675:1690 The present work 1675:1690 The present work systematically investigated the sequence signature for O-GlcNAcylation. 24760753 6 86 theme amino 838:842 arg1 preference 849:858 their amino acid preference 832:858 their amino acid preference 832:858 Based on the sequence, a peptide panel was designed to investigate key positions affecting O-GlcNAcylation of peptides and their amino acid preference. 24760753 8 87 theme crystalline 1132:1142 arg1 α 1144:1144 bovine crystalline α 1125:1144 bovine crystalline α 1125:1144 The amino acid preference at key positions was further investigated on bovine crystalline α via site-directed mutagenesis. 24760753 2 88 theme O-GlcNAc 252:259 arg1 status 261:266 O-GlcNAc status 252:266 O-GlcNAc status on numerous proteins 252:287 But O-GlcNAc status on numerous proteins remains unknown. 24760753 13 89 theme further 1842:1848 arg1 studies 1861:1867 further functional studies 1842:1867 further functional studies 1842:1867 The result will contribute to predicting the O-GlcNAc status of a protein and further functional studies. 24760753 11 90 theme Western 1661:1667 arg1 blot 1669:1672 Western blot 1661:1672 Western blot 1661:1672 To test the rule, 2 O-GlcNAcylation sites on sOGT (S52 and T449) were predicted and confirmed by Western blot. 24760753 7 91 dep positions 885:893 arg1 -1 900:901 -1 900:901 -1 900:901 It was indicated that 3 positions (-2, -1, and +2) had an important role for this modification, where the presence of uncharged amino acids with small side chains could confer high reactivity. 24760753 7 91 dep positions 885:893 arg1 +2 908:909 +2 908:909 +2 908:909 It was indicated that 3 positions (-2, -1, and +2) had an important role for this modification, where the presence of uncharged amino acids with small side chains could confer high reactivity. 24760753 5 92 from analysis 570:577 arg1 peptides 602:609 many O-GlcNAcylated peptides 582:609 many O-GlcNAcylated peptides 582:609 Frequency analysis on many O-GlcNAcylated peptides revealed a signature sequence, PPVS/TSATT, around the modification site (underlined, position 0). 25982853 12 0 theme analyses 2309:2316 arg1 prediction 2331:2340 protein classification, similarity analyses and function prediction 2274:2340 protein classification, similarity analyses and function prediction 2274:2340 This software is intended to provide a useful tool for general-purpose encoding of protein sequences and structures for applications is protein classification, similarity analyses and function prediction. 25982853 5 1 dep analysis 896:903 arg1 means 867:871 means 867:871 means 867:871 We demonstrate, by means of principle component analysis and Shannon entropy tests, how ProtDCal's sequence-based descriptors provide new and more relevant information not encoded by currently available servers for sequence-based protein feature generation. 25982853 6 2 theme additional 1202:1211 arg1 information 1227:1237 additional complementary information 1202:1237 additional complementary information 1202:1237 The wide diversity of the 3D-structure-based features generated by ProtDCal is shown to provide additional complementary information and effectively completes its general protein encoding capability. 25982853 11 3 theme systems 2129:2135 arg1 characterization 2097:2112 the features-based characterization 2078:2112 the features-based characterization of polypeptide systems 2078:2135 Furthermore, we have shown that adding structure-based descriptors contributes non-redundant additional information to the features-based characterization of polypeptide systems. 25982853 8 4 theme glycosylation 1535:1547 arg1 sites 1549:1553 N-linked glycosylation sites 1526:1553 N-linked glycosylation sites 1526:1553 Classification performance compares favourably with that of contemporary predictors of N-linked glycosylation sites, in spite of not using domain-specific features as input information. 25982853 12 5 theme protein 2274:2280 arg1 classification 2282:2295 protein classification 2274:2295 protein classification 2274:2295 This software is intended to provide a useful tool for general-purpose encoding of protein sequences and structures for applications is protein classification, similarity analyses and function prediction. 25982853 4 6 theme software 718:725 arg1 ProtDCal 688:695 ProtDCal 688:695 ProtDCal 688:695 RESULTS: We here introduce ProtDCal, a new computational software suite capable of generating tens of thousands of features considering both sequence-based and 3D-structural descriptors. 25982853 4 6 theme software 718:725 arg1 suite 727:731 a new computational software suite 698:731 a new computational software suite capable of generating tens of thousands of features considering both sequence-based and 3D-structural descriptors 698:845 RESULTS: We here introduce ProtDCal, a new computational software suite capable of generating tens of thousands of features considering both sequence-based and 3D-structural descriptors. 25982853 1 7 theme databases 184:192 arg1 growth 142:147 The exponential growth 126:147 The exponential growth of protein structural and sequence databases 126:192 BACKGROUND: The exponential growth of protein structural and sequence databases is enabling multifaceted approaches to understanding the long sought sequence-structure-function relationship. 25982853 12 8 theme sequences 2229:2237 arg1 encoding 2209:2216 general-purpose encoding 2193:2216 general-purpose encoding of protein sequences and structures 2193:2252 This software is intended to provide a useful tool for general-purpose encoding of protein sequences and structures for applications is protein classification, similarity analyses and function prediction. 25982853 4 9 theme capable 733:739 arg1 ProtDCal 688:695 ProtDCal 688:695 ProtDCal 688:695 RESULTS: We here introduce ProtDCal, a new computational software suite capable of generating tens of thousands of features considering both sequence-based and 3D-structural descriptors. 25982853 4 9 theme capable 733:739 arg1 suite 727:731 a new computational software suite 698:731 a new computational software suite capable of generating tens of thousands of features considering both sequence-based and 3D-structural descriptors 698:845 RESULTS: We here introduce ProtDCal, a new computational software suite capable of generating tens of thousands of features considering both sequence-based and 3D-structural descriptors. 25982853 5 10 theme sequence-based 947:960 arg1 descriptors 962:972 ProtDCal's sequence-based descriptors 936:972 ProtDCal's sequence-based descriptors 936:972 We demonstrate, by means of principle component analysis and Shannon entropy tests, how ProtDCal's sequence-based descriptors provide new and more relevant information not encoded by currently available servers for sequence-based protein feature generation. 25982853 12 11 theme structures 2243:2252 arg1 encoding 2209:2216 general-purpose encoding 2193:2216 general-purpose encoding of protein sequences and structures 2193:2252 This software is intended to provide a useful tool for general-purpose encoding of protein sequences and structures for applications is protein classification, similarity analyses and function prediction. 25982853 3 12 theme structure 578:586 arg1 descriptors 542:552 meaningful numerical descriptors 521:552 meaningful numerical descriptors of protein sequence and structure 521:586 However, extracting meaningful numerical descriptors of protein sequence and structure is a key issue that requires an efficient and widely available solution. 25982853 5 13 theme entropy 917:923 arg1 tests 925:929 Shannon entropy tests 909:929 Shannon entropy tests 909:929 We demonstrate, by means of principle component analysis and Shannon entropy tests, how ProtDCal's sequence-based descriptors provide new and more relevant information not encoded by currently available servers for sequence-based protein feature generation. 25982853 12 14 theme general-purpose 2193:2207 arg1 encoding 2209:2216 general-purpose encoding 2193:2216 general-purpose encoding of protein sequences and structures 2193:2252 This software is intended to provide a useful tool for general-purpose encoding of protein sequences and structures for applications is protein classification, similarity analyses and function prediction. 25982853 7 15 link N-linked 1383:1390 arg1 sites 1406:1410 N-linked glycosylation sites 1383:1410 N-linked glycosylation sites 1383:1410 As demonstration of the utility of ProtDCal's features, prediction models of N-linked glycosylation sites are trained and evaluated. 25982853 8 16 theme input 1606:1610 arg1 information 1612:1622 input information 1606:1622 input information 1606:1622 Classification performance compares favourably with that of contemporary predictors of N-linked glycosylation sites, in spite of not using domain-specific features as input information. 25982853 4 17 theme new 700:702 arg1 ProtDCal 688:695 ProtDCal 688:695 ProtDCal 688:695 RESULTS: We here introduce ProtDCal, a new computational software suite capable of generating tens of thousands of features considering both sequence-based and 3D-structural descriptors. 25982853 4 17 theme new 700:702 arg1 suite 727:731 a new computational software suite 698:731 a new computational software suite capable of generating tens of thousands of features considering both sequence-based and 3D-structural descriptors 698:845 RESULTS: We here introduce ProtDCal, a new computational software suite capable of generating tens of thousands of features considering both sequence-based and 3D-structural descriptors. 25982853 11 18 theme non-redundant 2038:2050 arg1 information 2063:2073 non-redundant additional information 2038:2073 non-redundant additional information 2038:2073 Furthermore, we have shown that adding structure-based descriptors contributes non-redundant additional information to the features-based characterization of polypeptide systems. 25982853 5 19 theme relevant 995:1002 arg1 information 1004:1014 new and more relevant information 982:1014 new and more relevant information not encoded by currently available servers for sequence-based protein feature generation 982:1103 We demonstrate, by means of principle component analysis and Shannon entropy tests, how ProtDCal's sequence-based descriptors provide new and more relevant information not encoded by currently available servers for sequence-based protein feature generation. 25982853 8 20 link N-linked 1526:1533 arg1 sites 1549:1553 N-linked glycosylation sites 1526:1553 N-linked glycosylation sites 1526:1553 Classification performance compares favourably with that of contemporary predictors of N-linked glycosylation sites, in spite of not using domain-specific features as input information. 25982853 9 21 theme graphical 1686:1694 arg1 interface 1701:1709 cross-platform graphical user interface 1671:1709 cross-platform graphical user interface 1671:1709 CONCLUSIONS: ProtDCal provides a friendly and cross-platform graphical user interface, developed in the Java programming language and is freely available at: http://bioinf.sce.carleton.ca/ProtDCal/ . 25982853 1 22 theme exponential 130:140 arg1 growth 142:147 The exponential growth 126:147 The exponential growth of protein structural and sequence databases 126:192 BACKGROUND: The exponential growth of protein structural and sequence databases is enabling multifaceted approaches to understanding the long sought sequence-structure-function relationship. 25982853 12 23 theme function 2322:2329 arg1 prediction 2331:2340 protein classification, similarity analyses and function prediction 2274:2340 protein classification, similarity analyses and function prediction 2274:2340 This software is intended to provide a useful tool for general-purpose encoding of protein sequences and structures for applications is protein classification, similarity analyses and function prediction. 25982853 7 24 theme prediction 1362:1371 arg1 models 1373:1378 prediction models 1362:1378 prediction models of N-linked glycosylation sites 1362:1410 As demonstration of the utility of ProtDCal's features, prediction models of N-linked glycosylation sites are trained and evaluated. 25982853 7 24 theme prediction 1362:1371 arg1 demonstration 1309:1321 demonstration 1309:1321 demonstration of the utility of ProtDCal's features 1309:1359 As demonstration of the utility of ProtDCal's features, prediction models of N-linked glycosylation sites are trained and evaluated. 25982853 6 25 theme wide 1110:1113 arg1 diversity 1115:1123 The wide diversity 1106:1123 The wide diversity of the 3D-structure-based features generated by ProtDCal 1106:1180 The wide diversity of the 3D-structure-based features generated by ProtDCal is shown to provide additional complementary information and effectively completes its general protein encoding capability. 25982853 8 26 theme contemporary 1499:1510 arg1 predictors 1512:1521 contemporary predictors 1499:1521 contemporary predictors of N-linked glycosylation sites 1499:1553 Classification performance compares favourably with that of contemporary predictors of N-linked glycosylation sites, in spite of not using domain-specific features as input information. 25982853 12 27 theme useful 2177:2182 arg1 tool 2184:2187 a useful tool 2175:2187 a useful tool for general-purpose encoding of protein sequences and structures for applications is protein classification, similarity analyses and function prediction 2175:2340 This software is intended to provide a useful tool for general-purpose encoding of protein sequences and structures for applications is protein classification, similarity analyses and function prediction. 25982853 4 28 theme features 776:783 arg1 thousands 763:771 thousands 763:771 thousands of features considering both sequence-based and 3D-structural descriptors 763:845 RESULTS: We here introduce ProtDCal, a new computational software suite capable of generating tens of thousands of features considering both sequence-based and 3D-structural descriptors. 25982853 10 29 theme group-based 1855:1865 arg1 encoding 1867:1874 local and group-based encoding 1845:1874 local and group-based encoding which enhances the diversity of the information captured by the computed features 1845:1956 ProtDCal introduces local and group-based encoding which enhances the diversity of the information captured by the computed features. 25982853 7 30 theme utility 1330:1336 arg1 models 1373:1378 prediction models 1362:1378 prediction models of N-linked glycosylation sites 1362:1410 As demonstration of the utility of ProtDCal's features, prediction models of N-linked glycosylation sites are trained and evaluated. 25982853 7 30 theme utility 1330:1336 arg1 demonstration 1309:1321 demonstration 1309:1321 demonstration of the utility of ProtDCal's features 1309:1359 As demonstration of the utility of ProtDCal's features, prediction models of N-linked glycosylation sites are trained and evaluated. 25982853 5 31 theme protein 1078:1084 arg1 generation 1094:1103 sequence-based protein feature generation 1063:1103 sequence-based protein feature generation 1063:1103 We demonstrate, by means of principle component analysis and Shannon entropy tests, how ProtDCal's sequence-based descriptors provide new and more relevant information not encoded by currently available servers for sequence-based protein feature generation. 25982853 4 32 theme sequence-based 802:815 arg1 descriptors 835:845 both sequence-based and 3D-structural descriptors 797:845 both sequence-based and 3D-structural descriptors 797:845 RESULTS: We here introduce ProtDCal, a new computational software suite capable of generating tens of thousands of features considering both sequence-based and 3D-structural descriptors. 25982853 10 33 theme local 1845:1849 arg1 encoding 1867:1874 local and group-based encoding 1845:1874 local and group-based encoding which enhances the diversity of the information captured by the computed features 1845:1956 ProtDCal introduces local and group-based encoding which enhances the diversity of the information captured by the computed features. 25982853 5 34 theme component 886:894 arg1 analysis 896:903 principle component analysis 876:903 principle component analysis 876:903 We demonstrate, by means of principle component analysis and Shannon entropy tests, how ProtDCal's sequence-based descriptors provide new and more relevant information not encoded by currently available servers for sequence-based protein feature generation. 25982853 4 35 theme 3D-structural 821:833 arg1 descriptors 835:845 both sequence-based and 3D-structural descriptors 797:845 both sequence-based and 3D-structural descriptors 797:845 RESULTS: We here introduce ProtDCal, a new computational software suite capable of generating tens of thousands of features considering both sequence-based and 3D-structural descriptors. 25982853 3 36 theme meaningful 521:530 arg1 descriptors 542:552 meaningful numerical descriptors 521:552 meaningful numerical descriptors of protein sequence and structure 521:586 However, extracting meaningful numerical descriptors of protein sequence and structure is a key issue that requires an efficient and widely available solution. 25982853 5 37 theme available 1041:1049 arg1 servers 1051:1057 currently available servers 1031:1057 currently available servers for sequence-based protein feature generation 1031:1103 We demonstrate, by means of principle component analysis and Shannon entropy tests, how ProtDCal's sequence-based descriptors provide new and more relevant information not encoded by currently available servers for sequence-based protein feature generation. 25982853 12 38 dep applications 2258:2269 arg1 prediction 2331:2340 protein classification, similarity analyses and function prediction 2274:2340 protein classification, similarity analyses and function prediction 2274:2340 This software is intended to provide a useful tool for general-purpose encoding of protein sequences and structures for applications is protein classification, similarity analyses and function prediction. 25982853 6 39 theme 3D-structure-based 1132:1149 arg1 features 1151:1158 the 3D-structure-based features 1128:1158 the 3D-structure-based features generated by ProtDCal 1128:1180 The wide diversity of the 3D-structure-based features generated by ProtDCal is shown to provide additional complementary information and effectively completes its general protein encoding capability. 25982853 2 40 theme pattern 392:398 arg1 techniques 412:421 and pattern recognition techniques 388:421 techniques 412:421 Advances in computation now make it possible to apply well-established data mining and pattern recognition techniques to these data to learn models that effectively relate structure and function. 25982853 10 41 theme information 1912:1922 arg1 diversity 1895:1903 the diversity 1891:1903 the diversity of the information captured by the computed features 1891:1956 ProtDCal introduces local and group-based encoding which enhances the diversity of the information captured by the computed features. 25982853 0 42 theme general-purpose-numerical 31:55 arg1 descriptors 57:67 general-purpose-numerical descriptors 31:67 general-purpose-numerical descriptors 31:67 ProtDCal: A program to compute general-purpose-numerical descriptors for sequences and 3D-structures of proteins. 25982853 8 43 theme domain-specific 1578:1592 arg1 features 1594:1601 domain-specific features 1578:1601 domain-specific features 1578:1601 Classification performance compares favourably with that of contemporary predictors of N-linked glycosylation sites, in spite of not using domain-specific features as input information. 25982853 6 44 theme complementary 1213:1225 arg1 information 1227:1237 additional complementary information 1202:1237 additional complementary information 1202:1237 The wide diversity of the 3D-structure-based features generated by ProtDCal is shown to provide additional complementary information and effectively completes its general protein encoding capability. 25982853 10 45 theme computed 1940:1947 arg1 features 1949:1956 the computed features 1936:1956 the computed features 1936:1956 ProtDCal introduces local and group-based encoding which enhances the diversity of the information captured by the computed features. 25982853 1 46 theme sought 256:261 arg1 relationship 291:302 the long sought sequence-structure-function relationship 247:302 the long sought sequence-structure-function relationship 247:302 BACKGROUND: The exponential growth of protein structural and sequence databases is enabling multifaceted approaches to understanding the long sought sequence-structure-function relationship. 25982853 12 47 theme classification 2282:2295 arg1 prediction 2331:2340 protein classification, similarity analyses and function prediction 2274:2340 protein classification, similarity analyses and function prediction 2274:2340 This software is intended to provide a useful tool for general-purpose encoding of protein sequences and structures for applications is protein classification, similarity analyses and function prediction. 25982853 0 48 dep ProtDCal 0:7 arg1 program 12:18 A program 10:18 ProtDCal: A program to compute general-purpose-numerical descriptors for sequences and 3D-structures of proteins. 0:112 ProtDCal: A program to compute general-purpose-numerical descriptors for sequences and 3D-structures of proteins. 25982853 7 49 theme glycosylation 1392:1404 arg1 sites 1406:1410 N-linked glycosylation sites 1383:1410 N-linked glycosylation sites 1383:1410 As demonstration of the utility of ProtDCal's features, prediction models of N-linked glycosylation sites are trained and evaluated. 25982853 11 50 theme polypeptide 2117:2127 arg1 systems 2129:2135 polypeptide systems 2117:2135 polypeptide systems 2117:2135 Furthermore, we have shown that adding structure-based descriptors contributes non-redundant additional information to the features-based characterization of polypeptide systems. 25982853 12 51 theme similarity 2298:2307 arg1 analyses 2309:2316 similarity analyses 2298:2316 similarity analyses 2298:2316 This software is intended to provide a useful tool for general-purpose encoding of protein sequences and structures for applications is protein classification, similarity analyses and function prediction. 25982853 2 52 theme recognition 400:410 arg1 techniques 412:421 and pattern recognition techniques 388:421 techniques 412:421 Advances in computation now make it possible to apply well-established data mining and pattern recognition techniques to these data to learn models that effectively relate structure and function. 25982853 5 53 theme new 982:984 arg1 information 1004:1014 new and more relevant information 982:1014 new and more relevant information not encoded by currently available servers for sequence-based protein feature generation 982:1103 We demonstrate, by means of principle component analysis and Shannon entropy tests, how ProtDCal's sequence-based descriptors provide new and more relevant information not encoded by currently available servers for sequence-based protein feature generation. 25982853 3 54 theme protein 557:563 arg1 sequence 565:572 protein sequence 557:572 protein sequence 557:572 However, extracting meaningful numerical descriptors of protein sequence and structure is a key issue that requires an efficient and widely available solution. 25982853 3 55 theme key 593:595 arg1 issue 597:601 a key issue 591:601 a key issue that requires an efficient and widely available solution 591:658 However, extracting meaningful numerical descriptors of protein sequence and structure is a key issue that requires an efficient and widely available solution. 25982853 1 56 theme sequence 175:182 arg1 databases 184:192 protein structural and sequence databases 152:192 databases 184:192 BACKGROUND: The exponential growth of protein structural and sequence databases is enabling multifaceted approaches to understanding the long sought sequence-structure-function relationship. 25982853 4 57 theme computational 704:716 arg1 ProtDCal 688:695 ProtDCal 688:695 ProtDCal 688:695 RESULTS: We here introduce ProtDCal, a new computational software suite capable of generating tens of thousands of features considering both sequence-based and 3D-structural descriptors. 25982853 4 57 theme computational 704:716 arg1 suite 727:731 a new computational software suite 698:731 a new computational software suite capable of generating tens of thousands of features considering both sequence-based and 3D-structural descriptors 698:845 RESULTS: We here introduce ProtDCal, a new computational software suite capable of generating tens of thousands of features considering both sequence-based and 3D-structural descriptors. 25982853 2 58 theme well-established 359:374 arg1 data 376:379 well-established data 359:379 well-established data mining and pattern recognition techniques to these data 359:435 Advances in computation now make it possible to apply well-established data mining and pattern recognition techniques to these data to learn models that effectively relate structure and function. 25982853 12 59 theme protein 2221:2227 arg1 sequences 2229:2237 protein sequences 2221:2237 protein sequences 2221:2237 This software is intended to provide a useful tool for general-purpose encoding of protein sequences and structures for applications is protein classification, similarity analyses and function prediction. 25982853 5 60 theme Shannon 909:915 arg1 tests 925:929 Shannon entropy tests 909:929 Shannon entropy tests 909:929 We demonstrate, by means of principle component analysis and Shannon entropy tests, how ProtDCal's sequence-based descriptors provide new and more relevant information not encoded by currently available servers for sequence-based protein feature generation. 25982853 6 61 theme general 1269:1275 arg1 protein 1277:1283 its general protein 1265:1283 its general protein encoding capability 1265:1303 The wide diversity of the 3D-structure-based features generated by ProtDCal is shown to provide additional complementary information and effectively completes its general protein encoding capability. 25982853 11 62 theme structure-based 1998:2012 arg1 descriptors 2014:2024 structure-based descriptors 1998:2024 structure-based descriptors 1998:2024 Furthermore, we have shown that adding structure-based descriptors contributes non-redundant additional information to the features-based characterization of polypeptide systems. 25982853 3 63 theme available 641:649 arg1 solution 651:658 an efficient and widely available solution 617:658 an efficient and widely available solution 617:658 However, extracting meaningful numerical descriptors of protein sequence and structure is a key issue that requires an efficient and widely available solution. 25982853 4 64 theme thousands 763:771 arg1 tens 755:758 tens 755:758 tens of thousands of features considering both sequence-based and 3D-structural descriptors 755:845 RESULTS: We here introduce ProtDCal, a new computational software suite capable of generating tens of thousands of features considering both sequence-based and 3D-structural descriptors. 25982853 11 65 theme additional 2052:2061 arg1 information 2063:2073 non-redundant additional information 2038:2073 non-redundant additional information 2038:2073 Furthermore, we have shown that adding structure-based descriptors contributes non-redundant additional information to the features-based characterization of polypeptide systems. 25982853 0 66 dep program 12:18 arg1 compute 23:29 compute 23:29 to compute general-purpose-numerical descriptors for sequences and 3D-structures of proteins 20:111 ProtDCal: A program to compute general-purpose-numerical descriptors for sequences and 3D-structures of proteins. 25982853 9 67 theme cross-platform 1671:1684 arg1 interface 1701:1709 cross-platform graphical user interface 1671:1709 cross-platform graphical user interface 1671:1709 CONCLUSIONS: ProtDCal provides a friendly and cross-platform graphical user interface, developed in the Java programming language and is freely available at: http://bioinf.sce.carleton.ca/ProtDCal/ . 25982853 8 68 theme Classification 1439:1452 arg1 performance 1454:1464 Classification performance 1439:1464 Classification performance 1439:1464 Classification performance compares favourably with that of contemporary predictors of N-linked glycosylation sites, in spite of not using domain-specific features as input information. 25982853 1 69 theme multifaceted 206:217 arg1 approaches 219:228 multifaceted approaches 206:228 multifaceted approaches to understanding the long sought sequence-structure-function relationship 206:302 BACKGROUND: The exponential growth of protein structural and sequence databases is enabling multifaceted approaches to understanding the long sought sequence-structure-function relationship. 25982853 9 70 theme user 1696:1699 arg1 interface 1701:1709 cross-platform graphical user interface 1671:1709 cross-platform graphical user interface 1671:1709 CONCLUSIONS: ProtDCal provides a friendly and cross-platform graphical user interface, developed in the Java programming language and is freely available at: http://bioinf.sce.carleton.ca/ProtDCal/ . 25982853 1 71 theme structural 160:169 arg1 growth 142:147 The exponential growth 126:147 The exponential growth of protein structural and sequence databases 126:192 BACKGROUND: The exponential growth of protein structural and sequence databases is enabling multifaceted approaches to understanding the long sought sequence-structure-function relationship. 25982853 0 72 theme proteins 104:111 arg1 3D-structures 87:99 3D-structures 87:99 3D-structures 87:99 ProtDCal: A program to compute general-purpose-numerical descriptors for sequences and 3D-structures of proteins. 25982853 0 72 theme proteins 104:111 arg1 sequences 73:81 sequences 73:81 sequences 73:81 ProtDCal: A program to compute general-purpose-numerical descriptors for sequences and 3D-structures of proteins. 25982853 3 73 theme efficient 620:628 arg1 solution 651:658 an efficient and widely available solution 617:658 an efficient and widely available solution 617:658 However, extracting meaningful numerical descriptors of protein sequence and structure is a key issue that requires an efficient and widely available solution. 25982853 5 74 theme sequence-based 1063:1076 arg1 generation 1094:1103 sequence-based protein feature generation 1063:1103 sequence-based protein feature generation 1063:1103 We demonstrate, by means of principle component analysis and Shannon entropy tests, how ProtDCal's sequence-based descriptors provide new and more relevant information not encoded by currently available servers for sequence-based protein feature generation. 25982853 5 75 theme principle 876:884 arg1 analysis 896:903 principle component analysis 876:903 principle component analysis 876:903 We demonstrate, by means of principle component analysis and Shannon entropy tests, how ProtDCal's sequence-based descriptors provide new and more relevant information not encoded by currently available servers for sequence-based protein feature generation. 25982853 8 76 theme N-linked 1526:1533 arg1 sites 1549:1553 N-linked glycosylation sites 1526:1553 N-linked glycosylation sites 1526:1553 Classification performance compares favourably with that of contemporary predictors of N-linked glycosylation sites, in spite of not using domain-specific features as input information. 25982853 7 77 gly glycosylation 1392:1404 arg2 sites 1406:1410 N-linked glycosylation sites 1383:1410 N-linked glycosylation sites 1383:1410 As demonstration of the utility of ProtDCal's features, prediction models of N-linked glycosylation sites are trained and evaluated. 25982853 9 78 from http 1783:1786 arg1 available 1769:1777 available 1769:1777 available 1769:1777 CONCLUSIONS: ProtDCal provides a friendly and cross-platform graphical user interface, developed in the Java programming language and is freely available at: http://bioinf.sce.carleton.ca/ProtDCal/ . 25982853 9 78 from http 1783:1786 arg1 CONCLUSIONS 1625:1635 CONCLUSIONS 1625:1635 CONCLUSIONS: ProtDCal provides a friendly and cross-platform graphical user interface, developed in the Java programming language and is freely available at: http://bioinf.sce.carleton.ca/ProtDCal/ . 1625:1823 CONCLUSIONS: ProtDCal provides a friendly and cross-platform graphical user interface, developed in the Java programming language and is freely available at: http://bioinf.sce.carleton.ca/ProtDCal/ . 25982853 9 79 theme Java 1729:1732 arg1 language 1746:1753 the Java programming language 1725:1753 the Java programming language 1725:1753 CONCLUSIONS: ProtDCal provides a friendly and cross-platform graphical user interface, developed in the Java programming language and is freely available at: http://bioinf.sce.carleton.ca/ProtDCal/ . 25982853 8 80 theme sites 1549:1553 arg1 predictors 1512:1521 contemporary predictors 1499:1521 contemporary predictors of N-linked glycosylation sites 1499:1553 Classification performance compares favourably with that of contemporary predictors of N-linked glycosylation sites, in spite of not using domain-specific features as input information. 25982853 3 81 theme numerical 532:540 arg1 descriptors 542:552 meaningful numerical descriptors 521:552 meaningful numerical descriptors of protein sequence and structure 521:586 However, extracting meaningful numerical descriptors of protein sequence and structure is a key issue that requires an efficient and widely available solution. 25982853 2 82 from Advances 305:312 arg1 computation 317:327 computation 317:327 computation 317:327 Advances in computation now make it possible to apply well-established data mining and pattern recognition techniques to these data to learn models that effectively relate structure and function. 25982853 6 83 theme features 1151:1158 arg1 diversity 1115:1123 The wide diversity 1106:1123 The wide diversity of the 3D-structure-based features generated by ProtDCal 1106:1180 The wide diversity of the 3D-structure-based features generated by ProtDCal is shown to provide additional complementary information and effectively completes its general protein encoding capability. 25982853 8 84 gly glycosylation 1535:1547 arg2 sites 1549:1553 N-linked glycosylation sites 1526:1553 N-linked glycosylation sites 1526:1553 Classification performance compares favourably with that of contemporary predictors of N-linked glycosylation sites, in spite of not using domain-specific features as input information. 25982853 3 85 theme sequence 565:572 arg1 descriptors 542:552 meaningful numerical descriptors 521:552 meaningful numerical descriptors of protein sequence and structure 521:586 However, extracting meaningful numerical descriptors of protein sequence and structure is a key issue that requires an efficient and widely available solution. 25982853 5 86 theme feature 1086:1092 arg1 generation 1094:1103 sequence-based protein feature generation 1063:1103 sequence-based protein feature generation 1063:1103 We demonstrate, by means of principle component analysis and Shannon entropy tests, how ProtDCal's sequence-based descriptors provide new and more relevant information not encoded by currently available servers for sequence-based protein feature generation. 25982853 7 87 theme sites 1406:1410 arg1 models 1373:1378 prediction models 1362:1378 prediction models of N-linked glycosylation sites 1362:1410 As demonstration of the utility of ProtDCal's features, prediction models of N-linked glycosylation sites are trained and evaluated. 25982853 7 87 theme sites 1406:1410 arg1 demonstration 1309:1321 demonstration 1309:1321 demonstration of the utility of ProtDCal's features 1309:1359 As demonstration of the utility of ProtDCal's features, prediction models of N-linked glycosylation sites are trained and evaluated. 25982853 9 88 theme programming 1734:1744 arg1 language 1746:1753 the Java programming language 1725:1753 the Java programming language 1725:1753 CONCLUSIONS: ProtDCal provides a friendly and cross-platform graphical user interface, developed in the Java programming language and is freely available at: http://bioinf.sce.carleton.ca/ProtDCal/ . 25982853 11 89 theme features-based 2082:2095 arg1 characterization 2097:2112 the features-based characterization 2078:2112 the features-based characterization of polypeptide systems 2078:2135 Furthermore, we have shown that adding structure-based descriptors contributes non-redundant additional information to the features-based characterization of polypeptide systems. 25982853 7 90 theme N-linked 1383:1390 arg1 sites 1406:1410 N-linked glycosylation sites 1383:1410 N-linked glycosylation sites 1383:1410 As demonstration of the utility of ProtDCal's features, prediction models of N-linked glycosylation sites are trained and evaluated. 25982853 1 91 theme sequence-structure-function 263:289 arg1 relationship 291:302 the long sought sequence-structure-function relationship 247:302 the long sought sequence-structure-function relationship 247:302 BACKGROUND: The exponential growth of protein structural and sequence databases is enabling multifaceted approaches to understanding the long sought sequence-structure-function relationship. 29020515 4 0 theme production 757:766 arg1 course 747:752 the course 743:752 the course of production 743:766 The objective of this evaluation was to show that the product profile of ETN drug substance (DS) has been consistent over the course of production. 29020515 8 1 dep indicates 1619:1627 arg1 18 years 1666:1673 18 years 1666:1673 18 years 1666:1673 Examination of results for all major quality attributes for ETN DS indicates a highly consistent process for over 18 years and throughout changes to the manufacturing process, without affecting safety and efficacy, as demonstrated across a wide range of clinical trials of ETN in multiple inflammatory diseases. 29020515 8 1 dep indicates 1619:1627 arg1 changes 1690:1696 changes 1690:1696 changes to the manufacturing process 1690:1725 Examination of results for all major quality attributes for ETN DS indicates a highly consistent process for over 18 years and throughout changes to the manufacturing process, without affecting safety and efficacy, as demonstrated across a wide range of clinical trials of ETN in multiple inflammatory diseases. 29020515 3 2 theme product 600:606 arg1 consistency 608:618 product consistency 600:618 product consistency 600:618 Successful manufacture of biologics, such as ETN, requires sophisticated process and product understanding, as well as meticulous control of operations to maintain product consistency. 29020515 2 3 theme hamster 288:294 arg1 cells 302:306 Chinese hamster ovary cells 280:306 Chinese hamster ovary cells 280:306 ETN is synthesized in Chinese hamster ovary cells by recombinant DNA technology as a fusion protein, with a fully human TNFRII ectodomain linked to the Fc portion of human IgG1. 29020515 6 4 theme ETN 1299:1301 arg1 DS 1303:1304 ETN DS 1299:1304 ETN DS 1299:1304 Based on the key quality attributes of product purity (assessed by hydrophobic interaction chromatography HPLC), binding activity (to TNF by ELISA), potency (inhibition of TNF-induced apoptosis by cell-based bioassay) and quality (N-linked oligosaccharide map), we show that the integrity of ETN DS has remained consistent over time. 29020515 1 5 theme necrosis 207:214 arg1 cytokine 248:255 a proinflammatory cytokine 230:255 a proinflammatory cytokine 230:255 Etanercept (ETN) (Enbrel®) is a soluble protein that binds to, and specifically inhibits, tumor necrosis factor (TNF), a proinflammatory cytokine. 29020515 1 5 theme necrosis 207:214 arg1 TNF 224:226 TNF 224:226 TNF 224:226 Etanercept (ETN) (Enbrel®) is a soluble protein that binds to, and specifically inhibits, tumor necrosis factor (TNF), a proinflammatory cytokine. 29020515 1 5 theme necrosis 207:214 arg1 protein 151:157 a soluble protein 141:157 a soluble protein that binds to, and specifically inhibits 141:198 Etanercept (ETN) (Enbrel®) is a soluble protein that binds to, and specifically inhibits, tumor necrosis factor (TNF), a proinflammatory cytokine. 29020515 1 5 theme necrosis 207:214 arg1 factor 216:221 tumor necrosis factor 201:221 tumor necrosis factor (TNF) 201:227 Etanercept (ETN) (Enbrel®) is a soluble protein that binds to, and specifically inhibits, tumor necrosis factor (TNF), a proinflammatory cytokine. 29020515 8 6 theme results 1567:1573 arg1 Examination 1552:1562 Examination 1552:1562 Examination of results for all major quality attributes for ETN DS 1552:1617 Examination of results for all major quality attributes for ETN DS indicates a highly consistent process for over 18 years and throughout changes to the manufacturing process, without affecting safety and efficacy, as demonstrated across a wide range of clinical trials of ETN in multiple inflammatory diseases. 29020515 6 7 theme product 1046:1052 arg1 purity 1054:1059 product purity 1046:1059 product purity (assessed by hydrophobic interaction chromatography HPLC) 1046:1117 Based on the key quality attributes of product purity (assessed by hydrophobic interaction chromatography HPLC), binding activity (to TNF by ELISA), potency (inhibition of TNF-induced apoptosis by cell-based bioassay) and quality (N-linked oligosaccharide map), we show that the integrity of ETN DS has remained consistent over time. 29020515 6 8 dep potency 1156:1162 arg1 inhibition 1165:1174 inhibition 1165:1174 inhibition of TNF-induced apoptosis by cell-based bioassay 1165:1222 Based on the key quality attributes of product purity (assessed by hydrophobic interaction chromatography HPLC), binding activity (to TNF by ELISA), potency (inhibition of TNF-induced apoptosis by cell-based bioassay) and quality (N-linked oligosaccharide map), we show that the integrity of ETN DS has remained consistent over time. 29020515 6 9 theme binding 1120:1126 arg1 activity 1128:1135 binding activity 1120:1135 binding activity (to TNF by ELISA) 1120:1153 Based on the key quality attributes of product purity (assessed by hydrophobic interaction chromatography HPLC), binding activity (to TNF by ELISA), potency (inhibition of TNF-induced apoptosis by cell-based bioassay) and quality (N-linked oligosaccharide map), we show that the integrity of ETN DS has remained consistent over time. 29020515 8 10 theme quality 1589:1595 arg1 attributes 1597:1606 all major quality attributes 1579:1606 all major quality attributes for ETN DS 1579:1617 Examination of results for all major quality attributes for ETN DS indicates a highly consistent process for over 18 years and throughout changes to the manufacturing process, without affecting safety and efficacy, as demonstrated across a wide range of clinical trials of ETN in multiple inflammatory diseases. 29020515 5 11 theme Multiple 769:776 arg1 analyses 801:808 Multiple orthogonal biochemical analyses 769:808 Multiple orthogonal biochemical analyses 769:808 Multiple orthogonal biochemical analyses, which included evaluation of attributes indicative of product purity, potency, and quality, were assessed on >2,000 batches of ETN from three sites of DS manufacture, during the period 1998-2015. 29020515 6 12 theme key 1020:1022 arg1 attributes 1032:1041 the key quality attributes 1016:1041 the key quality attributes of product purity (assessed by hydrophobic interaction chromatography HPLC), binding activity (to TNF by ELISA), potency (inhibition of TNF-induced apoptosis by cell-based bioassay) and quality (N-linked oligosaccharide map) 1016:1266 Based on the key quality attributes of product purity (assessed by hydrophobic interaction chromatography HPLC), binding activity (to TNF by ELISA), potency (inhibition of TNF-induced apoptosis by cell-based bioassay) and quality (N-linked oligosaccharide map), we show that the integrity of ETN DS has remained consistent over time. 29020515 6 13 theme apoptosis 1191:1199 arg1 inhibition 1165:1174 inhibition 1165:1174 inhibition of TNF-induced apoptosis by cell-based bioassay 1165:1222 Based on the key quality attributes of product purity (assessed by hydrophobic interaction chromatography HPLC), binding activity (to TNF by ELISA), potency (inhibition of TNF-induced apoptosis by cell-based bioassay) and quality (N-linked oligosaccharide map), we show that the integrity of ETN DS has remained consistent over time. 29020515 8 14 from ETN 1825:1827 arg1 diseases 1854:1861 multiple inflammatory diseases 1832:1861 multiple inflammatory diseases 1832:1861 Examination of results for all major quality attributes for ETN DS indicates a highly consistent process for over 18 years and throughout changes to the manufacturing process, without affecting safety and efficacy, as demonstrated across a wide range of clinical trials of ETN in multiple inflammatory diseases. 29020515 5 15 theme DS 962:963 arg1 manufacture 965:975 DS manufacture 962:975 DS manufacture 962:975 Multiple orthogonal biochemical analyses, which included evaluation of attributes indicative of product purity, potency, and quality, were assessed on >2,000 batches of ETN from three sites of DS manufacture, during the period 1998-2015. 29020515 7 16 theme detailed 1469:1476 arg1 assessments 1492:1502 detailed comparability assessments 1469:1502 detailed comparability assessments 1469:1502 This consistency was maintained through three major enhancements to the initial process of manufacturing that were supported by detailed comparability assessments, and approved by the European Medicines Agency. 29020515 8 17 from trials 1815:1820 arg1 diseases 1854:1861 multiple inflammatory diseases 1832:1861 multiple inflammatory diseases 1832:1861 Examination of results for all major quality attributes for ETN DS indicates a highly consistent process for over 18 years and throughout changes to the manufacturing process, without affecting safety and efficacy, as demonstrated across a wide range of clinical trials of ETN in multiple inflammatory diseases. 29020515 8 18 theme clinical 1806:1813 arg1 trials 1815:1820 clinical trials 1806:1820 clinical trials of ETN in multiple inflammatory diseases 1806:1861 Examination of results for all major quality attributes for ETN DS indicates a highly consistent process for over 18 years and throughout changes to the manufacturing process, without affecting safety and efficacy, as demonstrated across a wide range of clinical trials of ETN in multiple inflammatory diseases. 29020515 8 19 theme wide 1792:1795 arg1 range 1797:1801 a wide range 1790:1801 a wide range of clinical trials of ETN in multiple inflammatory diseases 1790:1861 Examination of results for all major quality attributes for ETN DS indicates a highly consistent process for over 18 years and throughout changes to the manufacturing process, without affecting safety and efficacy, as demonstrated across a wide range of clinical trials of ETN in multiple inflammatory diseases. 29020515 3 20 theme sophisticated 495:507 arg1 process 509:515 sophisticated process 495:515 sophisticated process 495:515 Successful manufacture of biologics, such as ETN, requires sophisticated process and product understanding, as well as meticulous control of operations to maintain product consistency. 29020515 8 21 from diseases 1854:1861 arg1 trials 1815:1820 clinical trials 1806:1820 clinical trials of ETN in multiple inflammatory diseases 1806:1861 Examination of results for all major quality attributes for ETN DS indicates a highly consistent process for over 18 years and throughout changes to the manufacturing process, without affecting safety and efficacy, as demonstrated across a wide range of clinical trials of ETN in multiple inflammatory diseases. 29020515 6 22 theme interaction 1086:1096 arg1 chromatography 1098:1111 hydrophobic interaction chromatography 1074:1111 hydrophobic interaction chromatography HPLC 1074:1116 Based on the key quality attributes of product purity (assessed by hydrophobic interaction chromatography HPLC), binding activity (to TNF by ELISA), potency (inhibition of TNF-induced apoptosis by cell-based bioassay) and quality (N-linked oligosaccharide map), we show that the integrity of ETN DS has remained consistent over time. 29020515 4 23 theme evaluation 643:652 arg1 objective 625:633 The objective 621:633 The objective of this evaluation 621:652 The objective of this evaluation was to show that the product profile of ETN drug substance (DS) has been consistent over the course of production. 29020515 8 24 theme ETN 1825:1827 arg1 trials 1815:1820 clinical trials 1806:1820 clinical trials of ETN in multiple inflammatory diseases 1806:1861 Examination of results for all major quality attributes for ETN DS indicates a highly consistent process for over 18 years and throughout changes to the manufacturing process, without affecting safety and efficacy, as demonstrated across a wide range of clinical trials of ETN in multiple inflammatory diseases. 29020515 8 25 theme consistent 1638:1647 arg1 process 1649:1655 a highly consistent process 1629:1655 a highly consistent process 1629:1655 Examination of results for all major quality attributes for ETN DS indicates a highly consistent process for over 18 years and throughout changes to the manufacturing process, without affecting safety and efficacy, as demonstrated across a wide range of clinical trials of ETN in multiple inflammatory diseases. 29020515 8 26 theme trials 1815:1820 arg1 range 1797:1801 a wide range 1790:1801 a wide range of clinical trials of ETN in multiple inflammatory diseases 1790:1861 Examination of results for all major quality attributes for ETN DS indicates a highly consistent process for over 18 years and throughout changes to the manufacturing process, without affecting safety and efficacy, as demonstrated across a wide range of clinical trials of ETN in multiple inflammatory diseases. 29020515 5 27 theme biochemical 789:799 arg1 analyses 801:808 Multiple orthogonal biochemical analyses 769:808 Multiple orthogonal biochemical analyses 769:808 Multiple orthogonal biochemical analyses, which included evaluation of attributes indicative of product purity, potency, and quality, were assessed on >2,000 batches of ETN from three sites of DS manufacture, during the period 1998-2015. 29020515 2 28 theme Fc 410:411 arg1 portion 413:419 the Fc portion 406:419 the Fc portion of human IgG1 406:433 ETN is synthesized in Chinese hamster ovary cells by recombinant DNA technology as a fusion protein, with a fully human TNFRII ectodomain linked to the Fc portion of human IgG1. 29020515 0 29 theme product 62:68 arg1 quality 70:76 product quality 62:76 product quality 62:76 Manufacturing history of etanercept (Enbrel®): Consistency of product quality through major process revisions. 29020515 2 30 attach linked 396:401 arg1 portion 413:419 the Fc portion 406:419 the Fc portion of human IgG1 406:433 ETN is synthesized in Chinese hamster ovary cells by recombinant DNA technology as a fusion protein, with a fully human TNFRII ectodomain linked to the Fc portion of human IgG1. 29020515 2 30 attach linked 396:401 arg2 ectodomain 385:394 a fully human TNFRII ectodomain 364:394 a fully human TNFRII ectodomain linked to the Fc portion of human IgG1 364:433 ETN is synthesized in Chinese hamster ovary cells by recombinant DNA technology as a fusion protein, with a fully human TNFRII ectodomain linked to the Fc portion of human IgG1. 29020515 7 31 theme initial 1413:1419 arg1 process 1421:1427 the initial process 1409:1427 the initial process of manufacturing that were supported by detailed comparability assessments 1409:1502 This consistency was maintained through three major enhancements to the initial process of manufacturing that were supported by detailed comparability assessments, and approved by the European Medicines Agency. 29020515 4 32 theme product 675:681 arg1 consistent 727:736 consistent 727:736 consistent 727:736 The objective of this evaluation was to show that the product profile of ETN drug substance (DS) has been consistent over the course of production. 29020515 4 32 theme product 675:681 arg1 profile 683:689 the product profile 671:689 the product profile of ETN drug substance (DS) 671:716 The objective of this evaluation was to show that the product profile of ETN drug substance (DS) has been consistent over the course of production. 29020515 8 33 theme multiple 1832:1839 arg1 diseases 1854:1861 multiple inflammatory diseases 1832:1861 multiple inflammatory diseases 1832:1861 Examination of results for all major quality attributes for ETN DS indicates a highly consistent process for over 18 years and throughout changes to the manufacturing process, without affecting safety and efficacy, as demonstrated across a wide range of clinical trials of ETN in multiple inflammatory diseases. 29020515 2 34 theme IgG1 430:433 arg1 portion 413:419 the Fc portion 406:419 the Fc portion of human IgG1 406:433 ETN is synthesized in Chinese hamster ovary cells by recombinant DNA technology as a fusion protein, with a fully human TNFRII ectodomain linked to the Fc portion of human IgG1. 29020515 6 35 link N-linked 1238:1245 arg1 map 1263:1265 N-linked oligosaccharide map 1238:1265 N-linked oligosaccharide map 1238:1265 Based on the key quality attributes of product purity (assessed by hydrophobic interaction chromatography HPLC), binding activity (to TNF by ELISA), potency (inhibition of TNF-induced apoptosis by cell-based bioassay) and quality (N-linked oligosaccharide map), we show that the integrity of ETN DS has remained consistent over time. 29020515 6 35 link N-linked 1238:1245 arg1 quality 1229:1235 quality 1229:1235 quality (N-linked oligosaccharide map) 1229:1266 Based on the key quality attributes of product purity (assessed by hydrophobic interaction chromatography HPLC), binding activity (to TNF by ELISA), potency (inhibition of TNF-induced apoptosis by cell-based bioassay) and quality (N-linked oligosaccharide map), we show that the integrity of ETN DS has remained consistent over time. 29020515 0 36 theme process 92:98 arg1 revisions 100:108 major process revisions 86:108 major process revisions 86:108 Manufacturing history of etanercept (Enbrel®): Consistency of product quality through major process revisions. 29020515 2 37 theme human 372:376 arg1 ectodomain 385:394 a fully human TNFRII ectodomain 364:394 a fully human TNFRII ectodomain linked to the Fc portion of human IgG1 364:433 ETN is synthesized in Chinese hamster ovary cells by recombinant DNA technology as a fusion protein, with a fully human TNFRII ectodomain linked to the Fc portion of human IgG1. 29020515 2 38 theme DNA 323:325 arg1 technology 327:336 recombinant DNA technology 311:336 recombinant DNA technology 311:336 ETN is synthesized in Chinese hamster ovary cells by recombinant DNA technology as a fusion protein, with a fully human TNFRII ectodomain linked to the Fc portion of human IgG1. 29020515 8 39 theme manufacturing 1705:1717 arg1 process 1719:1725 the manufacturing process 1701:1725 the manufacturing process 1701:1725 Examination of results for all major quality attributes for ETN DS indicates a highly consistent process for over 18 years and throughout changes to the manufacturing process, without affecting safety and efficacy, as demonstrated across a wide range of clinical trials of ETN in multiple inflammatory diseases. 29020515 5 40 theme indicative 851:860 arg1 attributes 840:849 attributes 840:849 attributes indicative of product purity, potency, and quality 840:900 Multiple orthogonal biochemical analyses, which included evaluation of attributes indicative of product purity, potency, and quality, were assessed on >2,000 batches of ETN from three sites of DS manufacture, during the period 1998-2015. 29020515 5 41 theme product 865:871 arg1 purity 873:878 product purity 865:878 product purity 865:878 Multiple orthogonal biochemical analyses, which included evaluation of attributes indicative of product purity, potency, and quality, were assessed on >2,000 batches of ETN from three sites of DS manufacture, during the period 1998-2015. 29020515 2 42 theme fusion 343:348 arg1 protein 350:356 a fusion protein 341:356 a fusion protein 341:356 ETN is synthesized in Chinese hamster ovary cells by recombinant DNA technology as a fusion protein, with a fully human TNFRII ectodomain linked to the Fc portion of human IgG1. 29020515 2 42 theme fusion 343:348 arg1 ETN 258:260 ETN 258:260 ETN 258:260 ETN is synthesized in Chinese hamster ovary cells by recombinant DNA technology as a fusion protein, with a fully human TNFRII ectodomain linked to the Fc portion of human IgG1. 29020515 1 43 theme proinflammatory 232:246 arg1 cytokine 248:255 a proinflammatory cytokine 230:255 a proinflammatory cytokine 230:255 Etanercept (ETN) (Enbrel®) is a soluble protein that binds to, and specifically inhibits, tumor necrosis factor (TNF), a proinflammatory cytokine. 29020515 1 43 theme proinflammatory 232:246 arg1 factor 216:221 tumor necrosis factor 201:221 tumor necrosis factor (TNF) 201:227 Etanercept (ETN) (Enbrel®) is a soluble protein that binds to, and specifically inhibits, tumor necrosis factor (TNF), a proinflammatory cytokine. 29020515 6 44 theme N-linked 1238:1245 arg1 map 1263:1265 N-linked oligosaccharide map 1238:1265 N-linked oligosaccharide map 1238:1265 Based on the key quality attributes of product purity (assessed by hydrophobic interaction chromatography HPLC), binding activity (to TNF by ELISA), potency (inhibition of TNF-induced apoptosis by cell-based bioassay) and quality (N-linked oligosaccharide map), we show that the integrity of ETN DS has remained consistent over time. 29020515 6 44 theme N-linked 1238:1245 arg1 quality 1229:1235 quality 1229:1235 quality (N-linked oligosaccharide map) 1229:1266 Based on the key quality attributes of product purity (assessed by hydrophobic interaction chromatography HPLC), binding activity (to TNF by ELISA), potency (inhibition of TNF-induced apoptosis by cell-based bioassay) and quality (N-linked oligosaccharide map), we show that the integrity of ETN DS has remained consistent over time. 29020515 2 45 theme Chinese 280:286 arg1 cells 302:306 Chinese hamster ovary cells 280:306 Chinese hamster ovary cells 280:306 ETN is synthesized in Chinese hamster ovary cells by recombinant DNA technology as a fusion protein, with a fully human TNFRII ectodomain linked to the Fc portion of human IgG1. 29020515 4 46 theme drug 698:701 arg1 substance 703:711 ETN drug substance 694:711 ETN drug substance (DS) 694:716 The objective of this evaluation was to show that the product profile of ETN drug substance (DS) has been consistent over the course of production. 29020515 4 46 theme drug 698:701 arg1 DS 714:715 DS 714:715 DS 714:715 The objective of this evaluation was to show that the product profile of ETN drug substance (DS) has been consistent over the course of production. 29020515 5 47 theme quality 894:900 arg1 indicative 851:860 indicative 851:860 indicative 851:860 Multiple orthogonal biochemical analyses, which included evaluation of attributes indicative of product purity, potency, and quality, were assessed on >2,000 batches of ETN from three sites of DS manufacture, during the period 1998-2015. 29020515 3 48 theme operations 577:586 arg1 process 509:515 sophisticated process 495:515 sophisticated process 495:515 Successful manufacture of biologics, such as ETN, requires sophisticated process and product understanding, as well as meticulous control of operations to maintain product consistency. 29020515 3 48 theme operations 577:586 arg1 understanding 529:541 product understanding 521:541 product understanding 521:541 Successful manufacture of biologics, such as ETN, requires sophisticated process and product understanding, as well as meticulous control of operations to maintain product consistency. 29020515 3 48 theme operations 577:586 arg1 control 566:572 meticulous control 555:572 meticulous control of operations 555:586 Successful manufacture of biologics, such as ETN, requires sophisticated process and product understanding, as well as meticulous control of operations to maintain product consistency. 29020515 0 49 dep Manufacturing 0:12 arg1 Consistency 47:57 Consistency 47:57 Consistency of product quality through major process revisions 47:108 Manufacturing history of etanercept (Enbrel®): Consistency of product quality through major process revisions. 29020515 2 50 theme ovary 296:300 arg1 cells 302:306 Chinese hamster ovary cells 280:306 Chinese hamster ovary cells 280:306 ETN is synthesized in Chinese hamster ovary cells by recombinant DNA technology as a fusion protein, with a fully human TNFRII ectodomain linked to the Fc portion of human IgG1. 29020515 6 51 theme DS 1303:1304 arg1 integrity 1286:1294 the integrity 1282:1294 the integrity of ETN DS 1282:1304 Based on the key quality attributes of product purity (assessed by hydrophobic interaction chromatography HPLC), binding activity (to TNF by ELISA), potency (inhibition of TNF-induced apoptosis by cell-based bioassay) and quality (N-linked oligosaccharide map), we show that the integrity of ETN DS has remained consistent over time. 29020515 1 52 theme tumor 201:205 arg1 cytokine 248:255 a proinflammatory cytokine 230:255 a proinflammatory cytokine 230:255 Etanercept (ETN) (Enbrel®) is a soluble protein that binds to, and specifically inhibits, tumor necrosis factor (TNF), a proinflammatory cytokine. 29020515 1 52 theme tumor 201:205 arg1 TNF 224:226 TNF 224:226 TNF 224:226 Etanercept (ETN) (Enbrel®) is a soluble protein that binds to, and specifically inhibits, tumor necrosis factor (TNF), a proinflammatory cytokine. 29020515 1 52 theme tumor 201:205 arg1 protein 151:157 a soluble protein 141:157 a soluble protein that binds to, and specifically inhibits 141:198 Etanercept (ETN) (Enbrel®) is a soluble protein that binds to, and specifically inhibits, tumor necrosis factor (TNF), a proinflammatory cytokine. 29020515 1 52 theme tumor 201:205 arg1 factor 216:221 tumor necrosis factor 201:221 tumor necrosis factor (TNF) 201:227 Etanercept (ETN) (Enbrel®) is a soluble protein that binds to, and specifically inhibits, tumor necrosis factor (TNF), a proinflammatory cytokine. 29020515 3 53 theme biologics 462:470 arg1 manufacture 447:457 Successful manufacture 436:457 Successful manufacture of biologics, such as ETN, 436:484 Successful manufacture of biologics, such as ETN, requires sophisticated process and product understanding, as well as meticulous control of operations to maintain product consistency. 29020515 6 54 theme purity 1054:1059 arg1 attributes 1032:1041 the key quality attributes 1016:1041 the key quality attributes of product purity (assessed by hydrophobic interaction chromatography HPLC), binding activity (to TNF by ELISA), potency (inhibition of TNF-induced apoptosis by cell-based bioassay) and quality (N-linked oligosaccharide map) 1016:1266 Based on the key quality attributes of product purity (assessed by hydrophobic interaction chromatography HPLC), binding activity (to TNF by ELISA), potency (inhibition of TNF-induced apoptosis by cell-based bioassay) and quality (N-linked oligosaccharide map), we show that the integrity of ETN DS has remained consistent over time. 29020515 6 55 theme quality 1229:1235 arg1 attributes 1032:1041 the key quality attributes 1016:1041 the key quality attributes of product purity (assessed by hydrophobic interaction chromatography HPLC), binding activity (to TNF by ELISA), potency (inhibition of TNF-induced apoptosis by cell-based bioassay) and quality (N-linked oligosaccharide map) 1016:1266 Based on the key quality attributes of product purity (assessed by hydrophobic interaction chromatography HPLC), binding activity (to TNF by ELISA), potency (inhibition of TNF-induced apoptosis by cell-based bioassay) and quality (N-linked oligosaccharide map), we show that the integrity of ETN DS has remained consistent over time. 29020515 6 56 theme activity 1128:1135 arg1 attributes 1032:1041 the key quality attributes 1016:1041 the key quality attributes of product purity (assessed by hydrophobic interaction chromatography HPLC), binding activity (to TNF by ELISA), potency (inhibition of TNF-induced apoptosis by cell-based bioassay) and quality (N-linked oligosaccharide map) 1016:1266 Based on the key quality attributes of product purity (assessed by hydrophobic interaction chromatography HPLC), binding activity (to TNF by ELISA), potency (inhibition of TNF-induced apoptosis by cell-based bioassay) and quality (N-linked oligosaccharide map), we show that the integrity of ETN DS has remained consistent over time. 29020515 1 57 theme soluble 143:149 arg1 protein 151:157 a soluble protein 141:157 a soluble protein that binds to, and specifically inhibits 141:198 Etanercept (ETN) (Enbrel®) is a soluble protein that binds to, and specifically inhibits, tumor necrosis factor (TNF), a proinflammatory cytokine. 29020515 1 57 theme soluble 143:149 arg1 factor 216:221 tumor necrosis factor 201:221 tumor necrosis factor (TNF) 201:227 Etanercept (ETN) (Enbrel®) is a soluble protein that binds to, and specifically inhibits, tumor necrosis factor (TNF), a proinflammatory cytokine. 29020515 1 57 theme soluble 143:149 arg1 Etanercept 111:120 Etanercept 111:120 Etanercept (ETN) (Enbrel®) 111:136 Etanercept (ETN) (Enbrel®) is a soluble protein that binds to, and specifically inhibits, tumor necrosis factor (TNF), a proinflammatory cytokine. 29020515 6 58 theme quality 1024:1030 arg1 attributes 1032:1041 the key quality attributes 1016:1041 the key quality attributes of product purity (assessed by hydrophobic interaction chromatography HPLC), binding activity (to TNF by ELISA), potency (inhibition of TNF-induced apoptosis by cell-based bioassay) and quality (N-linked oligosaccharide map) 1016:1266 Based on the key quality attributes of product purity (assessed by hydrophobic interaction chromatography HPLC), binding activity (to TNF by ELISA), potency (inhibition of TNF-induced apoptosis by cell-based bioassay) and quality (N-linked oligosaccharide map), we show that the integrity of ETN DS has remained consistent over time. 29020515 5 59 from batches 927:933 arg1 sites 953:957 three sites 947:957 three sites of DS manufacture 947:975 Multiple orthogonal biochemical analyses, which included evaluation of attributes indicative of product purity, potency, and quality, were assessed on >2,000 batches of ETN from three sites of DS manufacture, during the period 1998-2015. 29020515 5 59 from batches 927:933 arg1 manufacture 965:975 DS manufacture 962:975 DS manufacture 962:975 Multiple orthogonal biochemical analyses, which included evaluation of attributes indicative of product purity, potency, and quality, were assessed on >2,000 batches of ETN from three sites of DS manufacture, during the period 1998-2015. 29020515 7 60 theme comparability 1478:1490 arg1 assessments 1492:1502 detailed comparability assessments 1469:1502 detailed comparability assessments 1469:1502 This consistency was maintained through three major enhancements to the initial process of manufacturing that were supported by detailed comparability assessments, and approved by the European Medicines Agency. 29020515 6 61 theme TNF-induced 1179:1189 arg1 apoptosis 1191:1199 TNF-induced apoptosis 1179:1199 TNF-induced apoptosis 1179:1199 Based on the key quality attributes of product purity (assessed by hydrophobic interaction chromatography HPLC), binding activity (to TNF by ELISA), potency (inhibition of TNF-induced apoptosis by cell-based bioassay) and quality (N-linked oligosaccharide map), we show that the integrity of ETN DS has remained consistent over time. 29020515 6 62 dep purity 1054:1059 arg1 assessed 1062:1069 assessed 1062:1069 assessed by hydrophobic interaction chromatography HPLC 1062:1116 Based on the key quality attributes of product purity (assessed by hydrophobic interaction chromatography HPLC), binding activity (to TNF by ELISA), potency (inhibition of TNF-induced apoptosis by cell-based bioassay) and quality (N-linked oligosaccharide map), we show that the integrity of ETN DS has remained consistent over time. 29020515 8 63 theme inflammatory 1841:1852 arg1 diseases 1854:1861 multiple inflammatory diseases 1832:1861 multiple inflammatory diseases 1832:1861 Examination of results for all major quality attributes for ETN DS indicates a highly consistent process for over 18 years and throughout changes to the manufacturing process, without affecting safety and efficacy, as demonstrated across a wide range of clinical trials of ETN in multiple inflammatory diseases. 29020515 5 64 theme manufacture 965:975 arg1 sites 953:957 three sites 947:957 three sites of DS manufacture 947:975 Multiple orthogonal biochemical analyses, which included evaluation of attributes indicative of product purity, potency, and quality, were assessed on >2,000 batches of ETN from three sites of DS manufacture, during the period 1998-2015. 29020515 5 64 theme manufacture 965:975 arg1 manufacture 965:975 DS manufacture 962:975 DS manufacture 962:975 Multiple orthogonal biochemical analyses, which included evaluation of attributes indicative of product purity, potency, and quality, were assessed on >2,000 batches of ETN from three sites of DS manufacture, during the period 1998-2015. 29020515 8 65 theme ETN 1612:1614 arg1 DS 1616:1617 ETN DS 1612:1617 ETN DS 1612:1617 Examination of results for all major quality attributes for ETN DS indicates a highly consistent process for over 18 years and throughout changes to the manufacturing process, without affecting safety and efficacy, as demonstrated across a wide range of clinical trials of ETN in multiple inflammatory diseases. 29020515 6 66 theme chromatography 1098:1111 arg1 HPLC 1113:1116 hydrophobic interaction chromatography HPLC 1074:1116 hydrophobic interaction chromatography HPLC 1074:1116 Based on the key quality attributes of product purity (assessed by hydrophobic interaction chromatography HPLC), binding activity (to TNF by ELISA), potency (inhibition of TNF-induced apoptosis by cell-based bioassay) and quality (N-linked oligosaccharide map), we show that the integrity of ETN DS has remained consistent over time. 29020515 6 67 theme potency 1156:1162 arg1 attributes 1032:1041 the key quality attributes 1016:1041 the key quality attributes of product purity (assessed by hydrophobic interaction chromatography HPLC), binding activity (to TNF by ELISA), potency (inhibition of TNF-induced apoptosis by cell-based bioassay) and quality (N-linked oligosaccharide map) 1016:1266 Based on the key quality attributes of product purity (assessed by hydrophobic interaction chromatography HPLC), binding activity (to TNF by ELISA), potency (inhibition of TNF-induced apoptosis by cell-based bioassay) and quality (N-linked oligosaccharide map), we show that the integrity of ETN DS has remained consistent over time. 29020515 5 68 theme ETN 938:940 arg1 batches 927:933 >2,000 batches 920:933 >2,000 batches of ETN from three sites of DS manufacture 920:975 Multiple orthogonal biochemical analyses, which included evaluation of attributes indicative of product purity, potency, and quality, were assessed on >2,000 batches of ETN from three sites of DS manufacture, during the period 1998-2015. 29020515 7 69 theme manufacturing 1432:1444 arg1 process 1421:1427 the initial process 1409:1427 the initial process of manufacturing that were supported by detailed comparability assessments 1409:1502 This consistency was maintained through three major enhancements to the initial process of manufacturing that were supported by detailed comparability assessments, and approved by the European Medicines Agency. 29020515 6 70 theme hydrophobic 1074:1084 arg1 chromatography 1098:1111 hydrophobic interaction chromatography 1074:1111 hydrophobic interaction chromatography HPLC 1074:1116 Based on the key quality attributes of product purity (assessed by hydrophobic interaction chromatography HPLC), binding activity (to TNF by ELISA), potency (inhibition of TNF-induced apoptosis by cell-based bioassay) and quality (N-linked oligosaccharide map), we show that the integrity of ETN DS has remained consistent over time. 29020515 8 71 theme major 1583:1587 arg1 attributes 1597:1606 all major quality attributes 1579:1606 all major quality attributes for ETN DS 1579:1617 Examination of results for all major quality attributes for ETN DS indicates a highly consistent process for over 18 years and throughout changes to the manufacturing process, without affecting safety and efficacy, as demonstrated across a wide range of clinical trials of ETN in multiple inflammatory diseases. 29020515 6 72 theme oligosaccharide 1247:1261 arg1 map 1263:1265 N-linked oligosaccharide map 1238:1265 N-linked oligosaccharide map 1238:1265 Based on the key quality attributes of product purity (assessed by hydrophobic interaction chromatography HPLC), binding activity (to TNF by ELISA), potency (inhibition of TNF-induced apoptosis by cell-based bioassay) and quality (N-linked oligosaccharide map), we show that the integrity of ETN DS has remained consistent over time. 29020515 6 72 theme oligosaccharide 1247:1261 arg1 quality 1229:1235 quality 1229:1235 quality (N-linked oligosaccharide map) 1229:1266 Based on the key quality attributes of product purity (assessed by hydrophobic interaction chromatography HPLC), binding activity (to TNF by ELISA), potency (inhibition of TNF-induced apoptosis by cell-based bioassay) and quality (N-linked oligosaccharide map), we show that the integrity of ETN DS has remained consistent over time. 29020515 3 73 theme product 521:527 arg1 understanding 529:541 product understanding 521:541 product understanding 521:541 Successful manufacture of biologics, such as ETN, requires sophisticated process and product understanding, as well as meticulous control of operations to maintain product consistency. 29020515 5 74 theme orthogonal 778:787 arg1 analyses 801:808 Multiple orthogonal biochemical analyses 769:808 Multiple orthogonal biochemical analyses 769:808 Multiple orthogonal biochemical analyses, which included evaluation of attributes indicative of product purity, potency, and quality, were assessed on >2,000 batches of ETN from three sites of DS manufacture, during the period 1998-2015. 29020515 0 75 theme quality 70:76 arg1 Consistency 47:57 Consistency 47:57 Consistency of product quality through major process revisions 47:108 Manufacturing history of etanercept (Enbrel®): Consistency of product quality through major process revisions. 29020515 8 76 dep safety 1746:1751 arg1 demonstrated 1770:1781 demonstrated 1770:1781 demonstrated across a wide range of clinical trials of ETN in multiple inflammatory diseases 1770:1861 Examination of results for all major quality attributes for ETN DS indicates a highly consistent process for over 18 years and throughout changes to the manufacturing process, without affecting safety and efficacy, as demonstrated across a wide range of clinical trials of ETN in multiple inflammatory diseases. 29020515 0 77 theme major 86:90 arg1 revisions 100:108 major process revisions 86:108 major process revisions 86:108 Manufacturing history of etanercept (Enbrel®): Consistency of product quality through major process revisions. 29020515 5 78 theme purity 873:878 arg1 indicative 851:860 indicative 851:860 indicative 851:860 Multiple orthogonal biochemical analyses, which included evaluation of attributes indicative of product purity, potency, and quality, were assessed on >2,000 batches of ETN from three sites of DS manufacture, during the period 1998-2015. 29020515 5 79 from sites 953:957 arg1 ETN 938:940 ETN 938:940 ETN from three sites of DS manufacture 938:975 Multiple orthogonal biochemical analyses, which included evaluation of attributes indicative of product purity, potency, and quality, were assessed on >2,000 batches of ETN from three sites of DS manufacture, during the period 1998-2015. 29020515 5 79 from sites 953:957 arg1 batches 927:933 >2,000 batches 920:933 >2,000 batches of ETN from three sites of DS manufacture 920:975 Multiple orthogonal biochemical analyses, which included evaluation of attributes indicative of product purity, potency, and quality, were assessed on >2,000 batches of ETN from three sites of DS manufacture, during the period 1998-2015. 29020515 5 80 theme potency 881:887 arg1 indicative 851:860 indicative 851:860 indicative 851:860 Multiple orthogonal biochemical analyses, which included evaluation of attributes indicative of product purity, potency, and quality, were assessed on >2,000 batches of ETN from three sites of DS manufacture, during the period 1998-2015. 29020515 2 81 theme human 424:428 arg1 IgG1 430:433 human IgG1 424:433 human IgG1 424:433 ETN is synthesized in Chinese hamster ovary cells by recombinant DNA technology as a fusion protein, with a fully human TNFRII ectodomain linked to the Fc portion of human IgG1. 29020515 5 82 theme attributes 840:849 arg1 evaluation 826:835 evaluation 826:835 evaluation of attributes indicative of product purity, potency, and quality 826:900 Multiple orthogonal biochemical analyses, which included evaluation of attributes indicative of product purity, potency, and quality, were assessed on >2,000 batches of ETN from three sites of DS manufacture, during the period 1998-2015. 29020515 2 83 theme recombinant 311:321 arg1 technology 327:336 recombinant DNA technology 311:336 recombinant DNA technology 311:336 ETN is synthesized in Chinese hamster ovary cells by recombinant DNA technology as a fusion protein, with a fully human TNFRII ectodomain linked to the Fc portion of human IgG1. 29020515 0 84 theme etanercept 25:34 arg1 history 14:20 history 14:20 history of etanercept (Enbrel®) 14:44 Manufacturing history of etanercept (Enbrel®): Consistency of product quality through major process revisions. 29020515 3 85 theme meticulous 555:564 arg1 control 566:572 meticulous control 555:572 meticulous control of operations 555:586 Successful manufacture of biologics, such as ETN, requires sophisticated process and product understanding, as well as meticulous control of operations to maintain product consistency. 29020515 7 86 theme major 1387:1391 arg1 enhancements 1393:1404 three major enhancements 1381:1404 three major enhancements to the initial process of manufacturing that were supported by detailed comparability assessments 1381:1502 This consistency was maintained through three major enhancements to the initial process of manufacturing that were supported by detailed comparability assessments, and approved by the European Medicines Agency. 29020515 6 87 theme cell-based 1204:1213 arg1 bioassay 1215:1222 cell-based bioassay 1204:1222 cell-based bioassay 1204:1222 Based on the key quality attributes of product purity (assessed by hydrophobic interaction chromatography HPLC), binding activity (to TNF by ELISA), potency (inhibition of TNF-induced apoptosis by cell-based bioassay) and quality (N-linked oligosaccharide map), we show that the integrity of ETN DS has remained consistent over time. 29020515 2 88 theme TNFRII 378:383 arg1 ectodomain 385:394 a fully human TNFRII ectodomain 364:394 a fully human TNFRII ectodomain linked to the Fc portion of human IgG1 364:433 ETN is synthesized in Chinese hamster ovary cells by recombinant DNA technology as a fusion protein, with a fully human TNFRII ectodomain linked to the Fc portion of human IgG1. 29020515 4 89 theme ETN 694:696 arg1 substance 703:711 ETN drug substance 694:711 ETN drug substance (DS) 694:716 The objective of this evaluation was to show that the product profile of ETN drug substance (DS) has been consistent over the course of production. 29020515 4 89 theme ETN 694:696 arg1 DS 714:715 DS 714:715 DS 714:715 The objective of this evaluation was to show that the product profile of ETN drug substance (DS) has been consistent over the course of production. 29020515 4 90 theme substance 703:711 arg1 consistent 727:736 consistent 727:736 consistent 727:736 The objective of this evaluation was to show that the product profile of ETN drug substance (DS) has been consistent over the course of production. 29020515 4 90 theme substance 703:711 arg1 profile 683:689 the product profile 671:689 the product profile of ETN drug substance (DS) 671:716 The objective of this evaluation was to show that the product profile of ETN drug substance (DS) has been consistent over the course of production. 29020515 3 91 theme Successful 436:445 arg1 manufacture 447:457 Successful manufacture 436:457 Successful manufacture of biologics, such as ETN, 436:484 Successful manufacture of biologics, such as ETN, requires sophisticated process and product understanding, as well as meticulous control of operations to maintain product consistency. 27458206 1 0 theme biological 159:168 arg1 processes 170:178 numerous biological processes 150:178 numerous biological processes 150:178 O-linked N-acetylglucosamine linkage (O-GlcNAcylation) to serine or threonine residues regulates numerous biological processes; however, its role in DNA damage response remains elusive. 27458206 3 1 theme O-GlcNAc 310:317 arg1 transferase 319:329 O-GlcNAc transferase 310:329 O-GlcNAc transferase (OGT) 310:335 O-GlcNAc transferase (OGT), the solo enzyme for O-GlcNAcylation, relocates to the sites of DNA damage and induces the O-GlcNAcylation of histone H2AX and mediator of DNA damage checkpoint 1 (MDC1). 27458206 3 1 theme O-GlcNAc 310:317 arg1 enzyme 347:352 the solo enzyme 338:352 the solo enzyme for O-GlcNAcylation 338:372 O-GlcNAc transferase (OGT), the solo enzyme for O-GlcNAcylation, relocates to the sites of DNA damage and induces the O-GlcNAcylation of histone H2AX and mediator of DNA damage checkpoint 1 (MDC1). 27458206 3 1 theme O-GlcNAc 310:317 arg1 OGT 332:334 OGT 332:334 OGT 332:334 O-GlcNAc transferase (OGT), the solo enzyme for O-GlcNAcylation, relocates to the sites of DNA damage and induces the O-GlcNAcylation of histone H2AX and mediator of DNA damage checkpoint 1 (MDC1). 27458206 4 2 theme double-strand 553:565 arg1 phosphorylation 581:595 DNA double-strand break-induced phosphorylation 549:595 DNA double-strand break-induced phosphorylation of H2AX and MDC1 549:612 The O-GlcNAcylation negatively regulates DNA double-strand break-induced phosphorylation of H2AX and MDC1 by restraining the expansion of these phosphorylation events from the sites of DNA damage. 27458206 1 3 theme O-linked 53:60 arg1 O-GlcNAcylation 91:105 O-GlcNAcylation 91:105 O-GlcNAcylation 91:105 O-linked N-acetylglucosamine linkage (O-GlcNAcylation) to serine or threonine residues regulates numerous biological processes; however, its role in DNA damage response remains elusive. 27458206 1 3 theme O-linked 53:60 arg1 linkage 82:88 O-linked N-acetylglucosamine linkage 53:88 O-linked N-acetylglucosamine linkage (O-GlcNAcylation) to serine or threonine residues 53:138 O-linked N-acetylglucosamine linkage (O-GlcNAcylation) to serine or threonine residues regulates numerous biological processes; however, its role in DNA damage response remains elusive. 27458206 4 4 theme DNA 693:695 arg1 damage 697:702 DNA damage 693:702 DNA damage 693:702 The O-GlcNAcylation negatively regulates DNA double-strand break-induced phosphorylation of H2AX and MDC1 by restraining the expansion of these phosphorylation events from the sites of DNA damage. 27458206 1 5 theme N-acetylglucosamine 62:80 arg1 O-GlcNAcylation 91:105 O-GlcNAcylation 91:105 O-GlcNAcylation 91:105 O-linked N-acetylglucosamine linkage (O-GlcNAcylation) to serine or threonine residues regulates numerous biological processes; however, its role in DNA damage response remains elusive. 27458206 1 5 theme N-acetylglucosamine 62:80 arg1 linkage 82:88 O-linked N-acetylglucosamine linkage 53:88 O-linked N-acetylglucosamine linkage (O-GlcNAcylation) to serine or threonine residues 53:138 O-linked N-acetylglucosamine linkage (O-GlcNAcylation) to serine or threonine residues regulates numerous biological processes; however, its role in DNA damage response remains elusive. 27458206 3 6 theme DNA 401:403 arg1 damage 405:410 DNA damage 401:410 DNA damage 401:410 O-GlcNAc transferase (OGT), the solo enzyme for O-GlcNAcylation, relocates to the sites of DNA damage and induces the O-GlcNAcylation of histone H2AX and mediator of DNA damage checkpoint 1 (MDC1). 27458206 1 7 link O-linked 53:60 arg1 O-GlcNAcylation 91:105 O-GlcNAcylation 91:105 O-GlcNAcylation 91:105 O-linked N-acetylglucosamine linkage (O-GlcNAcylation) to serine or threonine residues regulates numerous biological processes; however, its role in DNA damage response remains elusive. 27458206 1 7 link O-linked 53:60 arg1 linkage 82:88 O-linked N-acetylglucosamine linkage 53:88 O-linked N-acetylglucosamine linkage (O-GlcNAcylation) to serine or threonine residues 53:138 O-linked N-acetylglucosamine linkage (O-GlcNAcylation) to serine or threonine residues regulates numerous biological processes; however, its role in DNA damage response remains elusive. 27458206 3 8 theme damage 405:410 arg1 sites 392:396 the sites 388:396 the sites of DNA damage 388:410 O-GlcNAc transferase (OGT), the solo enzyme for O-GlcNAcylation, relocates to the sites of DNA damage and induces the O-GlcNAcylation of histone H2AX and mediator of DNA damage checkpoint 1 (MDC1). 27458206 3 8 theme damage 405:410 arg1 damage 405:410 DNA damage 401:410 DNA damage 401:410 O-GlcNAc transferase (OGT), the solo enzyme for O-GlcNAcylation, relocates to the sites of DNA damage and induces the O-GlcNAcylation of histone H2AX and mediator of DNA damage checkpoint 1 (MDC1). 27458206 5 9 theme molecular 738:746 arg1 mechanism 748:756 molecular mechanism 738:756 molecular mechanism 738:756 Therefore, our study reveals the molecular mechanism and biological function of OGT-dependent O-GlcNAcylation in response to DNA damage. 27458206 5 10 dep mechanism 748:756 arg1 the 734:736 the 734:736 the 734:736 Therefore, our study reveals the molecular mechanism and biological function of OGT-dependent O-GlcNAcylation in response to DNA damage. 27458206 5 11 theme OGT-dependent 785:797 arg1 O-GlcNAcylation 799:813 OGT-dependent O-GlcNAcylation 785:813 OGT-dependent O-GlcNAcylation 785:813 Therefore, our study reveals the molecular mechanism and biological function of OGT-dependent O-GlcNAcylation in response to DNA damage. 27458206 2 12 theme damage 293:298 arg1 response 300:307 DNA damage response 289:307 DNA damage response 289:307 Here, we found that O-GlcNAcylation is induced by DNA damage response. 27458206 0 13 theme damage 35:40 arg1 signaling 42:50 DNA damage signaling 31:50 DNA damage signaling 31:50 OGT restrains the expansion of DNA damage signaling. 27458206 3 14 theme solo 342:345 arg1 transferase 319:329 O-GlcNAc transferase 310:329 O-GlcNAc transferase (OGT) 310:335 O-GlcNAc transferase (OGT), the solo enzyme for O-GlcNAcylation, relocates to the sites of DNA damage and induces the O-GlcNAcylation of histone H2AX and mediator of DNA damage checkpoint 1 (MDC1). 27458206 3 14 theme solo 342:345 arg1 enzyme 347:352 the solo enzyme 338:352 the solo enzyme for O-GlcNAcylation 338:372 O-GlcNAc transferase (OGT), the solo enzyme for O-GlcNAcylation, relocates to the sites of DNA damage and induces the O-GlcNAcylation of histone H2AX and mediator of DNA damage checkpoint 1 (MDC1). 27458206 2 15 theme DNA 289:291 arg1 damage 293:298 DNA damage 289:298 DNA damage response 289:307 Here, we found that O-GlcNAcylation is induced by DNA damage response. 27458206 4 16 theme MDC1 609:612 arg1 phosphorylation 581:595 DNA double-strand break-induced phosphorylation 549:595 DNA double-strand break-induced phosphorylation of H2AX and MDC1 549:612 The O-GlcNAcylation negatively regulates DNA double-strand break-induced phosphorylation of H2AX and MDC1 by restraining the expansion of these phosphorylation events from the sites of DNA damage. 27458206 3 17 theme checkpoint 487:496 arg1 mediator 464:471 mediator 464:471 mediator of DNA damage checkpoint 1 (MDC1) 464:505 O-GlcNAc transferase (OGT), the solo enzyme for O-GlcNAcylation, relocates to the sites of DNA damage and induces the O-GlcNAcylation of histone H2AX and mediator of DNA damage checkpoint 1 (MDC1). 27458206 3 17 theme checkpoint 487:496 arg1 O-GlcNAcylation 428:442 the O-GlcNAcylation 424:442 the O-GlcNAcylation of histone H2AX 424:458 O-GlcNAc transferase (OGT), the solo enzyme for O-GlcNAcylation, relocates to the sites of DNA damage and induces the O-GlcNAcylation of histone H2AX and mediator of DNA damage checkpoint 1 (MDC1). 27458206 5 18 theme O-GlcNAcylation 799:813 arg1 mechanism 748:756 molecular mechanism 738:756 molecular mechanism 738:756 Therefore, our study reveals the molecular mechanism and biological function of OGT-dependent O-GlcNAcylation in response to DNA damage. 27458206 5 18 theme O-GlcNAcylation 799:813 arg1 function 773:780 biological function 762:780 biological function 762:780 Therefore, our study reveals the molecular mechanism and biological function of OGT-dependent O-GlcNAcylation in response to DNA damage. 27458206 4 19 theme events 668:673 arg1 expansion 633:641 the expansion 629:641 the expansion of these phosphorylation events from the sites of DNA damage 629:702 The O-GlcNAcylation negatively regulates DNA double-strand break-induced phosphorylation of H2AX and MDC1 by restraining the expansion of these phosphorylation events from the sites of DNA damage. 27458206 0 20 theme DNA 31:33 arg1 damage 35:40 DNA damage 31:40 DNA damage signaling 31:50 OGT restrains the expansion of DNA damage signaling. 27458206 5 21 theme DNA 830:832 arg1 damage 834:839 DNA damage 830:839 DNA damage 830:839 Therefore, our study reveals the molecular mechanism and biological function of OGT-dependent O-GlcNAcylation in response to DNA damage. 27458206 1 22 theme DNA 202:204 arg1 damage 206:211 DNA damage 202:211 DNA damage response 202:220 O-linked N-acetylglucosamine linkage (O-GlcNAcylation) to serine or threonine residues regulates numerous biological processes; however, its role in DNA damage response remains elusive. 27458206 4 23 theme H2AX 600:603 arg1 phosphorylation 581:595 DNA double-strand break-induced phosphorylation 549:595 DNA double-strand break-induced phosphorylation of H2AX and MDC1 549:612 The O-GlcNAcylation negatively regulates DNA double-strand break-induced phosphorylation of H2AX and MDC1 by restraining the expansion of these phosphorylation events from the sites of DNA damage. 27458206 1 24 theme damage 206:211 arg1 response 213:220 DNA damage response 202:220 DNA damage response 202:220 O-linked N-acetylglucosamine linkage (O-GlcNAcylation) to serine or threonine residues regulates numerous biological processes; however, its role in DNA damage response remains elusive. 27458206 0 25 theme signaling 42:50 arg1 expansion 18:26 the expansion 14:26 the expansion of DNA damage signaling 14:50 OGT restrains the expansion of DNA damage signaling. 27458206 3 26 theme H2AX 455:458 arg1 mediator 464:471 mediator 464:471 mediator of DNA damage checkpoint 1 (MDC1) 464:505 O-GlcNAc transferase (OGT), the solo enzyme for O-GlcNAcylation, relocates to the sites of DNA damage and induces the O-GlcNAcylation of histone H2AX and mediator of DNA damage checkpoint 1 (MDC1). 27458206 3 26 theme H2AX 455:458 arg1 O-GlcNAcylation 428:442 the O-GlcNAcylation 424:442 the O-GlcNAcylation of histone H2AX 424:458 O-GlcNAc transferase (OGT), the solo enzyme for O-GlcNAcylation, relocates to the sites of DNA damage and induces the O-GlcNAcylation of histone H2AX and mediator of DNA damage checkpoint 1 (MDC1). 27458206 1 27 dep serine 111:116 arg1 residues 131:138 residues 131:138 residues 131:138 O-linked N-acetylglucosamine linkage (O-GlcNAcylation) to serine or threonine residues regulates numerous biological processes; however, its role in DNA damage response remains elusive. 27458206 1 28 theme numerous 150:157 arg1 processes 170:178 numerous biological processes 150:178 numerous biological processes 150:178 O-linked N-acetylglucosamine linkage (O-GlcNAcylation) to serine or threonine residues regulates numerous biological processes; however, its role in DNA damage response remains elusive. 27458206 1 29 from role 194:197 arg1 response 213:220 DNA damage response 202:220 DNA damage response 202:220 O-linked N-acetylglucosamine linkage (O-GlcNAcylation) to serine or threonine residues regulates numerous biological processes; however, its role in DNA damage response remains elusive. 27458206 4 30 theme phosphorylation 652:666 arg1 events 668:673 these phosphorylation events 646:673 these phosphorylation events 646:673 The O-GlcNAcylation negatively regulates DNA double-strand break-induced phosphorylation of H2AX and MDC1 by restraining the expansion of these phosphorylation events from the sites of DNA damage. 27458206 4 31 theme damage 697:702 arg1 sites 684:688 the sites 680:688 the sites of DNA damage 680:702 The O-GlcNAcylation negatively regulates DNA double-strand break-induced phosphorylation of H2AX and MDC1 by restraining the expansion of these phosphorylation events from the sites of DNA damage. 27458206 4 31 theme damage 697:702 arg1 damage 697:702 DNA damage 693:702 DNA damage 693:702 The O-GlcNAcylation negatively regulates DNA double-strand break-induced phosphorylation of H2AX and MDC1 by restraining the expansion of these phosphorylation events from the sites of DNA damage. 27458206 3 32 theme histone 447:453 arg1 H2AX 455:458 histone H2AX 447:458 histone H2AX 447:458 O-GlcNAc transferase (OGT), the solo enzyme for O-GlcNAcylation, relocates to the sites of DNA damage and induces the O-GlcNAcylation of histone H2AX and mediator of DNA damage checkpoint 1 (MDC1). 27458206 4 33 theme break-induced 567:579 arg1 phosphorylation 581:595 DNA double-strand break-induced phosphorylation 549:595 DNA double-strand break-induced phosphorylation of H2AX and MDC1 549:612 The O-GlcNAcylation negatively regulates DNA double-strand break-induced phosphorylation of H2AX and MDC1 by restraining the expansion of these phosphorylation events from the sites of DNA damage. 27458206 3 34 theme DNA 476:478 arg1 damage 480:485 DNA damage 476:485 DNA damage checkpoint 1 (MDC1) 476:505 O-GlcNAc transferase (OGT), the solo enzyme for O-GlcNAcylation, relocates to the sites of DNA damage and induces the O-GlcNAcylation of histone H2AX and mediator of DNA damage checkpoint 1 (MDC1). 27458206 4 35 from sites 684:688 arg1 expansion 633:641 the expansion 629:641 the expansion of these phosphorylation events from the sites of DNA damage 629:702 The O-GlcNAcylation negatively regulates DNA double-strand break-induced phosphorylation of H2AX and MDC1 by restraining the expansion of these phosphorylation events from the sites of DNA damage. 27458206 4 36 theme DNA 549:551 arg1 phosphorylation 581:595 DNA double-strand break-induced phosphorylation 549:595 DNA double-strand break-induced phosphorylation of H2AX and MDC1 549:612 The O-GlcNAcylation negatively regulates DNA double-strand break-induced phosphorylation of H2AX and MDC1 by restraining the expansion of these phosphorylation events from the sites of DNA damage. 27458206 5 37 theme biological 762:771 arg1 function 773:780 biological function 762:780 biological function 762:780 Therefore, our study reveals the molecular mechanism and biological function of OGT-dependent O-GlcNAcylation in response to DNA damage. 27458206 3 38 theme damage 480:485 arg1 checkpoint 487:496 DNA damage checkpoint 1 476:498 DNA damage checkpoint 1 (MDC1) 476:505 O-GlcNAc transferase (OGT), the solo enzyme for O-GlcNAcylation, relocates to the sites of DNA damage and induces the O-GlcNAcylation of histone H2AX and mediator of DNA damage checkpoint 1 (MDC1). 27458206 3 38 theme damage 480:485 arg1 MDC1 501:504 MDC1 501:504 MDC1 501:504 O-GlcNAc transferase (OGT), the solo enzyme for O-GlcNAcylation, relocates to the sites of DNA damage and induces the O-GlcNAcylation of histone H2AX and mediator of DNA damage checkpoint 1 (MDC1). 24444746 0 0 theme conformational 86:99 arg1 properties 101:110 the conformational properties 82:110 the conformational properties of tau monomers 82:126 O-GlcNAc modification of tau directly inhibits its aggregation without perturbing the conformational properties of tau monomers. 24444746 7 1 theme enhanced 1276:1283 arg1 solubility 1293:1302 enhanced monomer solubility 1276:1302 enhanced monomer solubility 1276:1302 These data indicate that the inhibitory effects of O-GlcNAc on tau aggregation may result from enhanced monomer solubility or the destabilization of fibrils or soluble aggregates, rather than by altering the conformational properties of the monomeric protein. 24444746 1 2 theme protein 175:181 arg1 tau 183:185 the microtubule-associated protein tau 148:185 the microtubule-associated protein tau 148:185 The aggregation of the microtubule-associated protein tau into paired helical filaments to form neurofibrillary tangles constitutes one of the pathological hallmarks of Alzheimer's disease. 24444746 1 3 theme pathological 272:283 arg1 hallmarks 285:293 the pathological hallmarks 268:293 the pathological hallmarks of Alzheimer's disease 268:316 The aggregation of the microtubule-associated protein tau into paired helical filaments to form neurofibrillary tangles constitutes one of the pathological hallmarks of Alzheimer's disease. 24444746 7 4 theme monomer 1285:1291 arg1 solubility 1293:1302 enhanced monomer solubility 1276:1302 enhanced monomer solubility 1276:1302 These data indicate that the inhibitory effects of O-GlcNAc on tau aggregation may result from enhanced monomer solubility or the destabilization of fibrils or soluble aggregates, rather than by altering the conformational properties of the monomeric protein. 24444746 1 5 theme tau 183:185 arg1 aggregation 133:143 The aggregation 129:143 The aggregation of the microtubule-associated protein tau into paired helical filaments to form neurofibrillary tangles 129:247 The aggregation of the microtubule-associated protein tau into paired helical filaments to form neurofibrillary tangles constitutes one of the pathological hallmarks of Alzheimer's disease. 24444746 1 6 theme hallmarks 285:293 arg1 hallmarks 285:293 the pathological hallmarks 268:293 the pathological hallmarks of Alzheimer's disease 268:316 The aggregation of the microtubule-associated protein tau into paired helical filaments to form neurofibrillary tangles constitutes one of the pathological hallmarks of Alzheimer's disease. 24444746 1 6 theme hallmarks 285:293 arg1 one 261:263 one 261:263 one 261:263 The aggregation of the microtubule-associated protein tau into paired helical filaments to form neurofibrillary tangles constitutes one of the pathological hallmarks of Alzheimer's disease. 24444746 7 7 theme soluble 1341:1347 arg1 aggregates 1349:1358 soluble aggregates 1341:1358 soluble aggregates 1341:1358 These data indicate that the inhibitory effects of O-GlcNAc on tau aggregation may result from enhanced monomer solubility or the destabilization of fibrils or soluble aggregates, rather than by altering the conformational properties of the monomeric protein. 24444746 3 8 theme mouse 583:587 arg1 model 589:593 a tauopathy mouse model 571:593 a tauopathy mouse model 571:593 Previously, increased O-GlcNAcylation of tau has been shown to block the accumulation of tau aggregates within a tauopathy mouse model. 24444746 6 9 theme resonance 944:952 arg1 studies 954:960 nuclear magnetic resonance studies 927:960 nuclear magnetic resonance studies 927:960 Similarly, nuclear magnetic resonance studies demonstrated that O-GlcNAcylation only minimally perturbs the local structural and dynamic features of a tau fragment (residues 353-408) spanning the last microtubule binding repeat to the major GlcNAc-acceptor Ser400. 24444746 6 10 theme major 1151:1155 arg1 Ser400 1173:1178 the major GlcNAc-acceptor Ser400 1147:1178 the major GlcNAc-acceptor Ser400 1147:1178 Similarly, nuclear magnetic resonance studies demonstrated that O-GlcNAcylation only minimally perturbs the local structural and dynamic features of a tau fragment (residues 353-408) spanning the last microtubule binding repeat to the major GlcNAc-acceptor Ser400. 24444746 5 11 theme resonance 883:891 arg1 transfer 900:907 a Förster resonance energy transfer 873:907 a Förster resonance energy transfer assay 873:913 O-GlcNAcylation, however, does not impact the "global-fold" of tau as measured by a Förster resonance energy transfer assay. 24444746 0 12 theme monomers 119:126 arg1 properties 101:110 the conformational properties 82:110 the conformational properties of tau monomers 82:126 O-GlcNAc modification of tau directly inhibits its aggregation without perturbing the conformational properties of tau monomers. 24444746 2 13 link O-linked 398:405 arg1 N-acetyl-D-glucosamine 375:396 N-acetyl-D-glucosamine 375:396 N-acetyl-D-glucosamine O-linked to several serine and threonine residues (O-GlcNAc) 375:457 Tau is post-translationally modified by the addition of N-acetyl-D-glucosamine O-linked to several serine and threonine residues (O-GlcNAc). 24444746 2 14 dep serine 418:423 arg1 residues 439:446 residues 439:446 residues 439:446 Tau is post-translationally modified by the addition of N-acetyl-D-glucosamine O-linked to several serine and threonine residues (O-GlcNAc). 24444746 4 15 theme aggregation 712:722 arg1 extent 682:687 extent 682:687 extent 682:687 Here we show that O-GlcNAc modification of full-length human tau impairs the rate and extent of its heparin-induced aggregation without perturbing its activity toward microtubule polymerization. 24444746 4 15 theme aggregation 712:722 arg1 rate 673:676 rate 673:676 rate 673:676 Here we show that O-GlcNAc modification of full-length human tau impairs the rate and extent of its heparin-induced aggregation without perturbing its activity toward microtubule polymerization. 24444746 5 16 theme transfer 900:907 arg1 assay 909:913 a Förster resonance energy transfer assay 873:913 a Förster resonance energy transfer assay 873:913 O-GlcNAcylation, however, does not impact the "global-fold" of tau as measured by a Förster resonance energy transfer assay. 24444746 0 17 theme tau 115:117 arg1 monomers 119:126 tau monomers 115:126 tau monomers 115:126 O-GlcNAc modification of tau directly inhibits its aggregation without perturbing the conformational properties of tau monomers. 24444746 6 18 theme nuclear 927:933 arg1 resonance 944:952 nuclear magnetic resonance 927:952 nuclear magnetic resonance studies 927:960 Similarly, nuclear magnetic resonance studies demonstrated that O-GlcNAcylation only minimally perturbs the local structural and dynamic features of a tau fragment (residues 353-408) spanning the last microtubule binding repeat to the major GlcNAc-acceptor Ser400. 24444746 4 19 theme O-GlcNAc 614:621 arg1 modification 623:634 O-GlcNAc modification 614:634 O-GlcNAc modification of full-length human tau 614:659 Here we show that O-GlcNAc modification of full-length human tau impairs the rate and extent of its heparin-induced aggregation without perturbing its activity toward microtubule polymerization. 24444746 3 20 theme tauopathy 573:581 arg1 model 589:593 a tauopathy mouse model 571:593 a tauopathy mouse model 571:593 Previously, increased O-GlcNAcylation of tau has been shown to block the accumulation of tau aggregates within a tauopathy mouse model. 24444746 1 21 theme paired 192:197 arg1 filaments 207:215 paired helical filaments 192:215 paired helical filaments to form neurofibrillary tangles 192:247 The aggregation of the microtubule-associated protein tau into paired helical filaments to form neurofibrillary tangles constitutes one of the pathological hallmarks of Alzheimer's disease. 24444746 5 22 theme tau 854:856 arg1 " 849:849 the "global-fold" 833:849 the "global-fold" of tau 833:856 O-GlcNAcylation, however, does not impact the "global-fold" of tau as measured by a Förster resonance energy transfer assay. 24444746 6 23 dep residues 1081:1088 arg1 353-408 1090:1096 353-408 1090:1096 353-408 1090:1096 Similarly, nuclear magnetic resonance studies demonstrated that O-GlcNAcylation only minimally perturbs the local structural and dynamic features of a tau fragment (residues 353-408) spanning the last microtubule binding repeat to the major GlcNAc-acceptor Ser400. 24444746 6 24 theme magnetic 935:942 arg1 resonance 944:952 nuclear magnetic resonance 927:952 nuclear magnetic resonance studies 927:960 Similarly, nuclear magnetic resonance studies demonstrated that O-GlcNAcylation only minimally perturbs the local structural and dynamic features of a tau fragment (residues 353-408) spanning the last microtubule binding repeat to the major GlcNAc-acceptor Ser400. 24444746 6 25 theme binding 1129:1135 arg1 repeat 1137:1142 the last microtubule binding repeat 1108:1142 the last microtubule binding repeat to the major GlcNAc-acceptor Ser400 1108:1178 Similarly, nuclear magnetic resonance studies demonstrated that O-GlcNAcylation only minimally perturbs the local structural and dynamic features of a tau fragment (residues 353-408) spanning the last microtubule binding repeat to the major GlcNAc-acceptor Ser400. 24444746 1 26 theme helical 199:205 arg1 filaments 207:215 paired helical filaments 192:215 paired helical filaments to form neurofibrillary tangles 192:247 The aggregation of the microtubule-associated protein tau into paired helical filaments to form neurofibrillary tangles constitutes one of the pathological hallmarks of Alzheimer's disease. 24444746 0 27 theme O-GlcNAc 0:7 arg1 modification 9:20 O-GlcNAc modification 0:20 O-GlcNAc modification of tau 0:27 O-GlcNAc modification of tau directly inhibits its aggregation without perturbing the conformational properties of tau monomers. 24444746 6 28 theme dynamic 1045:1051 arg1 features 1053:1060 the local structural and dynamic features 1020:1060 the local structural and dynamic features of a tau fragment (residues 353-408) spanning the last microtubule binding repeat to the major GlcNAc-acceptor Ser400 1020:1178 Similarly, nuclear magnetic resonance studies demonstrated that O-GlcNAcylation only minimally perturbs the local structural and dynamic features of a tau fragment (residues 353-408) spanning the last microtubule binding repeat to the major GlcNAc-acceptor Ser400. 24444746 2 29 mod modified 347:354 arg3 addition 363:370 the addition 359:370 the addition of N-acetyl-D-glucosamine O-linked to several serine and threonine residues (O-GlcNAc) 359:457 Tau is post-translationally modified by the addition of N-acetyl-D-glucosamine O-linked to several serine and threonine residues (O-GlcNAc). 24444746 2 29 mod modified 347:354 arg1 Tau 319:321 Tau 319:321 Tau 319:321 Tau is post-translationally modified by the addition of N-acetyl-D-glucosamine O-linked to several serine and threonine residues (O-GlcNAc). 24444746 6 30 theme tau 1067:1069 arg1 residues 1081:1088 residues 353-408 1081:1096 residues 353-408 1081:1096 Similarly, nuclear magnetic resonance studies demonstrated that O-GlcNAcylation only minimally perturbs the local structural and dynamic features of a tau fragment (residues 353-408) spanning the last microtubule binding repeat to the major GlcNAc-acceptor Ser400. 24444746 6 30 theme tau 1067:1069 arg1 fragment 1071:1078 a tau fragment 1065:1078 a tau fragment (residues 353-408) spanning the last microtubule binding repeat to the major GlcNAc-acceptor Ser400 1065:1178 Similarly, nuclear magnetic resonance studies demonstrated that O-GlcNAcylation only minimally perturbs the local structural and dynamic features of a tau fragment (residues 353-408) spanning the last microtubule binding repeat to the major GlcNAc-acceptor Ser400. 24444746 3 31 theme increased 472:480 arg1 O-GlcNAcylation 482:496 increased O-GlcNAcylation 472:496 increased O-GlcNAcylation of tau 472:503 Previously, increased O-GlcNAcylation of tau has been shown to block the accumulation of tau aggregates within a tauopathy mouse model. 24444746 0 32 theme tau 25:27 arg1 modification 9:20 O-GlcNAc modification 0:20 O-GlcNAc modification of tau 0:27 O-GlcNAc modification of tau directly inhibits its aggregation without perturbing the conformational properties of tau monomers. 24444746 7 33 theme monomeric 1422:1430 arg1 protein 1432:1438 the monomeric protein 1418:1438 the monomeric protein 1418:1438 These data indicate that the inhibitory effects of O-GlcNAc on tau aggregation may result from enhanced monomer solubility or the destabilization of fibrils or soluble aggregates, rather than by altering the conformational properties of the monomeric protein. 24444746 6 34 theme last 1112:1115 arg1 repeat 1137:1142 the last microtubule binding repeat 1108:1142 the last microtubule binding repeat to the major GlcNAc-acceptor Ser400 1108:1178 Similarly, nuclear magnetic resonance studies demonstrated that O-GlcNAcylation only minimally perturbs the local structural and dynamic features of a tau fragment (residues 353-408) spanning the last microtubule binding repeat to the major GlcNAc-acceptor Ser400. 24444746 7 35 theme O-GlcNAc 1232:1239 arg1 effects 1221:1227 the inhibitory effects 1206:1227 the inhibitory effects of O-GlcNAc on tau aggregation 1206:1258 These data indicate that the inhibitory effects of O-GlcNAc on tau aggregation may result from enhanced monomer solubility or the destabilization of fibrils or soluble aggregates, rather than by altering the conformational properties of the monomeric protein. 24444746 6 36 theme structural 1030:1039 arg1 features 1053:1060 the local structural and dynamic features 1020:1060 the local structural and dynamic features of a tau fragment (residues 353-408) spanning the last microtubule binding repeat to the major GlcNAc-acceptor Ser400 1020:1178 Similarly, nuclear magnetic resonance studies demonstrated that O-GlcNAcylation only minimally perturbs the local structural and dynamic features of a tau fragment (residues 353-408) spanning the last microtubule binding repeat to the major GlcNAc-acceptor Ser400. 24444746 2 37 theme O-linked 398:405 arg1 N-acetyl-D-glucosamine 375:396 N-acetyl-D-glucosamine 375:396 N-acetyl-D-glucosamine O-linked to several serine and threonine residues (O-GlcNAc) 375:457 Tau is post-translationally modified by the addition of N-acetyl-D-glucosamine O-linked to several serine and threonine residues (O-GlcNAc). 24444746 5 38 theme Förster 875:881 arg1 transfer 900:907 a Förster resonance energy transfer 873:907 a Förster resonance energy transfer assay 873:913 O-GlcNAcylation, however, does not impact the "global-fold" of tau as measured by a Förster resonance energy transfer assay. 24444746 7 39 theme inhibitory 1210:1219 arg1 effects 1221:1227 the inhibitory effects 1206:1227 the inhibitory effects of O-GlcNAc on tau aggregation 1206:1258 These data indicate that the inhibitory effects of O-GlcNAc on tau aggregation may result from enhanced monomer solubility or the destabilization of fibrils or soluble aggregates, rather than by altering the conformational properties of the monomeric protein. 24444746 6 40 theme local 1024:1028 arg1 features 1053:1060 the local structural and dynamic features 1020:1060 the local structural and dynamic features of a tau fragment (residues 353-408) spanning the last microtubule binding repeat to the major GlcNAc-acceptor Ser400 1020:1178 Similarly, nuclear magnetic resonance studies demonstrated that O-GlcNAcylation only minimally perturbs the local structural and dynamic features of a tau fragment (residues 353-408) spanning the last microtubule binding repeat to the major GlcNAc-acceptor Ser400. 24444746 3 41 theme tau 501:503 arg1 O-GlcNAcylation 482:496 increased O-GlcNAcylation 472:496 increased O-GlcNAcylation of tau 472:503 Previously, increased O-GlcNAcylation of tau has been shown to block the accumulation of tau aggregates within a tauopathy mouse model. 24444746 4 42 theme heparin-induced 696:710 arg1 aggregation 712:722 its heparin-induced aggregation 692:722 its heparin-induced aggregation 692:722 Here we show that O-GlcNAc modification of full-length human tau impairs the rate and extent of its heparin-induced aggregation without perturbing its activity toward microtubule polymerization. 24444746 1 43 theme neurofibrillary 225:239 arg1 tangles 241:247 neurofibrillary tangles 225:247 neurofibrillary tangles 225:247 The aggregation of the microtubule-associated protein tau into paired helical filaments to form neurofibrillary tangles constitutes one of the pathological hallmarks of Alzheimer's disease. 24444746 5 44 theme global-fold 838:848 arg1 " 849:849 the "global-fold" 833:849 the "global-fold" of tau 833:856 O-GlcNAcylation, however, does not impact the "global-fold" of tau as measured by a Förster resonance energy transfer assay. 24444746 8 45 theme disease 1545:1551 arg1 therapeutics 1553:1564 potential Alzheimer's disease therapeutics 1523:1564 potential Alzheimer's disease therapeutics 1523:1564 This work further underscores the potential of targeting the O-GlcNAc pathway for potential Alzheimer's disease therapeutics. 24444746 1 46 dep filaments 207:215 arg1 form 220:223 form 220:223 to form neurofibrillary tangles 217:247 The aggregation of the microtubule-associated protein tau into paired helical filaments to form neurofibrillary tangles constitutes one of the pathological hallmarks of Alzheimer's disease. 24444746 5 47 theme energy 893:898 arg1 transfer 900:907 a Förster resonance energy transfer 873:907 a Förster resonance energy transfer assay 873:913 O-GlcNAcylation, however, does not impact the "global-fold" of tau as measured by a Förster resonance energy transfer assay. 24444746 7 48 theme aggregates 1349:1358 arg1 solubility 1293:1302 enhanced monomer solubility 1276:1302 enhanced monomer solubility 1276:1302 These data indicate that the inhibitory effects of O-GlcNAc on tau aggregation may result from enhanced monomer solubility or the destabilization of fibrils or soluble aggregates, rather than by altering the conformational properties of the monomeric protein. 24444746 7 48 theme aggregates 1349:1358 arg1 destabilization 1311:1325 the destabilization 1307:1325 the destabilization of fibrils or soluble aggregates 1307:1358 These data indicate that the inhibitory effects of O-GlcNAc on tau aggregation may result from enhanced monomer solubility or the destabilization of fibrils or soluble aggregates, rather than by altering the conformational properties of the monomeric protein. 24444746 4 49 dep rate 673:676 arg1 the 669:671 the 669:671 the 669:671 Here we show that O-GlcNAc modification of full-length human tau impairs the rate and extent of its heparin-induced aggregation without perturbing its activity toward microtubule polymerization. 24444746 2 50 theme N-acetyl-D-glucosamine 375:396 arg1 addition 363:370 the addition 359:370 the addition of N-acetyl-D-glucosamine O-linked to several serine and threonine residues (O-GlcNAc) 359:457 Tau is post-translationally modified by the addition of N-acetyl-D-glucosamine O-linked to several serine and threonine residues (O-GlcNAc). 24444746 7 51 from effects 1221:1227 arg1 aggregation 1248:1258 tau aggregation 1244:1258 tau aggregation 1244:1258 These data indicate that the inhibitory effects of O-GlcNAc on tau aggregation may result from enhanced monomer solubility or the destabilization of fibrils or soluble aggregates, rather than by altering the conformational properties of the monomeric protein. 24444746 7 52 theme conformational 1389:1402 arg1 properties 1404:1413 the conformational properties 1385:1413 the conformational properties of the monomeric protein 1385:1438 These data indicate that the inhibitory effects of O-GlcNAc on tau aggregation may result from enhanced monomer solubility or the destabilization of fibrils or soluble aggregates, rather than by altering the conformational properties of the monomeric protein. 24444746 3 53 theme tau 549:551 arg1 aggregates 553:562 tau aggregates 549:562 tau aggregates 549:562 Previously, increased O-GlcNAcylation of tau has been shown to block the accumulation of tau aggregates within a tauopathy mouse model. 24444746 8 54 theme potential 1523:1531 arg1 therapeutics 1553:1564 potential Alzheimer's disease therapeutics 1523:1564 potential Alzheimer's disease therapeutics 1523:1564 This work further underscores the potential of targeting the O-GlcNAc pathway for potential Alzheimer's disease therapeutics. 24444746 7 55 theme fibrils 1330:1336 arg1 solubility 1293:1302 enhanced monomer solubility 1276:1302 enhanced monomer solubility 1276:1302 These data indicate that the inhibitory effects of O-GlcNAc on tau aggregation may result from enhanced monomer solubility or the destabilization of fibrils or soluble aggregates, rather than by altering the conformational properties of the monomeric protein. 24444746 7 55 theme fibrils 1330:1336 arg1 destabilization 1311:1325 the destabilization 1307:1325 the destabilization of fibrils or soluble aggregates 1307:1358 These data indicate that the inhibitory effects of O-GlcNAc on tau aggregation may result from enhanced monomer solubility or the destabilization of fibrils or soluble aggregates, rather than by altering the conformational properties of the monomeric protein. 24444746 4 56 theme microtubule 763:773 arg1 polymerization 775:788 microtubule polymerization 763:788 microtubule polymerization 763:788 Here we show that O-GlcNAc modification of full-length human tau impairs the rate and extent of its heparin-induced aggregation without perturbing its activity toward microtubule polymerization. 24444746 8 57 theme O-GlcNAc 1502:1509 arg1 pathway 1511:1517 the O-GlcNAc pathway 1498:1517 the O-GlcNAc pathway for potential Alzheimer's disease therapeutics 1498:1564 This work further underscores the potential of targeting the O-GlcNAc pathway for potential Alzheimer's disease therapeutics. 24444746 7 58 theme protein 1432:1438 arg1 properties 1404:1413 the conformational properties 1385:1413 the conformational properties of the monomeric protein 1385:1438 These data indicate that the inhibitory effects of O-GlcNAc on tau aggregation may result from enhanced monomer solubility or the destabilization of fibrils or soluble aggregates, rather than by altering the conformational properties of the monomeric protein. 24444746 4 59 theme human 651:655 arg1 tau 657:659 full-length human tau 639:659 full-length human tau 639:659 Here we show that O-GlcNAc modification of full-length human tau impairs the rate and extent of its heparin-induced aggregation without perturbing its activity toward microtubule polymerization. 24444746 6 60 theme microtubule 1117:1127 arg1 repeat 1137:1142 the last microtubule binding repeat 1108:1142 the last microtubule binding repeat to the major GlcNAc-acceptor Ser400 1108:1178 Similarly, nuclear magnetic resonance studies demonstrated that O-GlcNAcylation only minimally perturbs the local structural and dynamic features of a tau fragment (residues 353-408) spanning the last microtubule binding repeat to the major GlcNAc-acceptor Ser400. 24444746 1 61 theme microtubule-associated 152:173 arg1 tau 183:185 the microtubule-associated protein tau 148:185 the microtubule-associated protein tau 148:185 The aggregation of the microtubule-associated protein tau into paired helical filaments to form neurofibrillary tangles constitutes one of the pathological hallmarks of Alzheimer's disease. 24444746 4 62 theme full-length 639:649 arg1 tau 657:659 full-length human tau 639:659 full-length human tau 639:659 Here we show that O-GlcNAc modification of full-length human tau impairs the rate and extent of its heparin-induced aggregation without perturbing its activity toward microtubule polymerization. 24444746 4 63 mod modification 623:634 arg3 O-GlcNAc 614:621 O-GlcNAc modification 614:634 O-GlcNAc modification of full-length human tau 614:659 Here we show that O-GlcNAc modification of full-length human tau impairs the rate and extent of its heparin-induced aggregation without perturbing its activity toward microtubule polymerization. 24444746 4 63 mod modification 623:634 arg1 tau 657:659 full-length human tau 639:659 full-length human tau 639:659 Here we show that O-GlcNAc modification of full-length human tau impairs the rate and extent of its heparin-induced aggregation without perturbing its activity toward microtubule polymerization. 24444746 6 64 theme GlcNAc-acceptor 1157:1171 arg1 Ser400 1173:1178 the major GlcNAc-acceptor Ser400 1147:1178 the major GlcNAc-acceptor Ser400 1147:1178 Similarly, nuclear magnetic resonance studies demonstrated that O-GlcNAcylation only minimally perturbs the local structural and dynamic features of a tau fragment (residues 353-408) spanning the last microtubule binding repeat to the major GlcNAc-acceptor Ser400. 24444746 3 65 theme aggregates 553:562 arg1 accumulation 533:544 the accumulation 529:544 the accumulation of tau aggregates within a tauopathy mouse model 529:593 Previously, increased O-GlcNAcylation of tau has been shown to block the accumulation of tau aggregates within a tauopathy mouse model. 24444746 6 66 theme fragment 1071:1078 arg1 features 1053:1060 the local structural and dynamic features 1020:1060 the local structural and dynamic features of a tau fragment (residues 353-408) spanning the last microtubule binding repeat to the major GlcNAc-acceptor Ser400 1020:1178 Similarly, nuclear magnetic resonance studies demonstrated that O-GlcNAcylation only minimally perturbs the local structural and dynamic features of a tau fragment (residues 353-408) spanning the last microtubule binding repeat to the major GlcNAc-acceptor Ser400. 24444746 2 67 theme several 410:416 arg1 O-GlcNAc 449:456 O-GlcNAc 449:456 O-GlcNAc 449:456 Tau is post-translationally modified by the addition of N-acetyl-D-glucosamine O-linked to several serine and threonine residues (O-GlcNAc). 24444746 2 67 theme several 410:416 arg1 serine 418:423 serine 418:423 serine 418:423 Tau is post-translationally modified by the addition of N-acetyl-D-glucosamine O-linked to several serine and threonine residues (O-GlcNAc). 24444746 7 68 theme tau 1244:1246 arg1 aggregation 1248:1258 tau aggregation 1244:1258 tau aggregation 1244:1258 These data indicate that the inhibitory effects of O-GlcNAc on tau aggregation may result from enhanced monomer solubility or the destabilization of fibrils or soluble aggregates, rather than by altering the conformational properties of the monomeric protein. 24444746 4 69 theme tau 657:659 arg1 modification 623:634 O-GlcNAc modification 614:634 O-GlcNAc modification of full-length human tau 614:659 Here we show that O-GlcNAc modification of full-length human tau impairs the rate and extent of its heparin-induced aggregation without perturbing its activity toward microtubule polymerization. 26197478 4 0 theme His6-tagged 628:638 arg1 Endo-CC1 640:647 recombinant His6-tagged Endo-CC1 616:647 recombinant His6-tagged Endo-CC1 616:647 We successfully expressed recombinant His6-tagged Endo-CC1 and Endo-CC2 in Escherichia coli and purified them for enzymatic characterization. 26197478 6 1 theme E. 901:902 arg1 cultures 909:916 E. coli cultures 901:916 E. coli cultures 901:916 Since Endo-CC1 could be prepared more easily than Endo-CC2 from E. coli cultures, we examined the enzymatic properties of Endo-CC1 in detail. 26197478 2 2 theme oligosaccharides 384:399 arg1 hydrolysis 351:360 the hydrolysis 347:360 the hydrolysis of human complex type oligosaccharides 347:399 However, there are only a few known ENGases that can catalyze the hydrolysis of human complex type oligosaccharides, and although commercially available, they are expensive. 26197478 7 3 theme complex 1204:1210 arg1 oligosaccharide 1212:1226 the sialotriantennary type complex oligosaccharide 1177:1226 the sialotriantennary type complex oligosaccharide of glycoprotein fetuin 1177:1249 Our results showed that Endo-CC1 acted on both N-linked high-mannose type and sialobiantennary type complex oligosaccharides of glycoproteins RNase B and human transferrin, respectively, but not on the sialotriantennary type complex oligosaccharide of glycoprotein fetuin. 26197478 5 4 from activity 777:784 arg1 complex 806:812 complex 806:812 complex 806:812 Both Endo-CC1 and Endo-CC2 showed hydrolytic activity on high-mannose and complex type oligosaccharides. 26197478 5 4 from activity 777:784 arg1 high-mannose 789:800 high-mannose 789:800 high-mannose 789:800 Both Endo-CC1 and Endo-CC2 showed hydrolytic activity on high-mannose and complex type oligosaccharides. 26197478 8 5 theme activity 1290:1297 arg1 Examination 1252:1262 Examination 1252:1262 Examination of the transglycosylation activity of Endo-CC1 1252:1309 Examination of the transglycosylation activity of Endo-CC1 revealed that the wild-type Endo-CC1 could not transfer the sialobiantennary type complex oligosaccharide onto the deglycosylated RNase B. To obtain an Endo-CC1 mutant with desired transglycosylation activity, we performed mutation analysis of the active site residue Asn 180 (N180), known to be important for catalysis, by individually replacing it with the remaining 19 amino acid residues. 26197478 7 6 theme sialotriantennary 1181:1197 arg1 oligosaccharide 1212:1226 the sialotriantennary type complex oligosaccharide 1177:1226 the sialotriantennary type complex oligosaccharide of glycoprotein fetuin 1177:1249 Our results showed that Endo-CC1 acted on both N-linked high-mannose type and sialobiantennary type complex oligosaccharides of glycoproteins RNase B and human transferrin, respectively, but not on the sialotriantennary type complex oligosaccharide of glycoprotein fetuin. 26197478 1 7 theme useful 216:221 arg1 tool 223:226 a useful tool 214:226 a useful tool for analyzing oligosaccharide contents of glycoproteins 214:282 Endo-β-N-acetylglucosaminidase (ENGase), which catalyzes hydrolysis of N-linked oligosaccharides, is a useful tool for analyzing oligosaccharide contents of glycoproteins. 26197478 1 7 theme useful 216:221 arg1 Endo-β-N-acetylglucosaminidase 113:142 Endo-β-N-acetylglucosaminidase 113:142 Endo-β-N-acetylglucosaminidase (ENGase) 113:151 Endo-β-N-acetylglucosaminidase (ENGase), which catalyzes hydrolysis of N-linked oligosaccharides, is a useful tool for analyzing oligosaccharide contents of glycoproteins. 26197478 8 8 theme Endo-CC1 1302:1309 arg1 activity 1290:1297 the transglycosylation activity 1267:1297 the transglycosylation activity of Endo-CC1 1267:1309 Examination of the transglycosylation activity of Endo-CC1 revealed that the wild-type Endo-CC1 could not transfer the sialobiantennary type complex oligosaccharide onto the deglycosylated RNase B. To obtain an Endo-CC1 mutant with desired transglycosylation activity, we performed mutation analysis of the active site residue Asn 180 (N180), known to be important for catalysis, by individually replacing it with the remaining 19 amino acid residues. 26197478 8 9 theme sialobiantennary 1371:1386 arg1 oligosaccharide 1401:1415 the sialobiantennary type complex oligosaccharide 1367:1415 the sialobiantennary type complex oligosaccharide 1367:1415 Examination of the transglycosylation activity of Endo-CC1 revealed that the wild-type Endo-CC1 could not transfer the sialobiantennary type complex oligosaccharide onto the deglycosylated RNase B. To obtain an Endo-CC1 mutant with desired transglycosylation activity, we performed mutation analysis of the active site residue Asn 180 (N180), known to be important for catalysis, by individually replacing it with the remaining 19 amino acid residues. 26197478 8 10 theme complex 1393:1399 arg1 oligosaccharide 1401:1415 the sialobiantennary type complex oligosaccharide 1367:1415 the sialobiantennary type complex oligosaccharide 1367:1415 Examination of the transglycosylation activity of Endo-CC1 revealed that the wild-type Endo-CC1 could not transfer the sialobiantennary type complex oligosaccharide onto the deglycosylated RNase B. To obtain an Endo-CC1 mutant with desired transglycosylation activity, we performed mutation analysis of the active site residue Asn 180 (N180), known to be important for catalysis, by individually replacing it with the remaining 19 amino acid residues. 26197478 3 11 theme fungus 539:544 arg1 cinerea 558:564 the basidiomycete fungus Coprinopsis cinerea 521:564 the basidiomycete fungus Coprinopsis cinerea 521:564 Here, we report the cloning of two ENGase encoding cDNAs from the basidiomycete fungus Coprinopsis cinerea, Endo-CC1 and Endo-CC2. 26197478 1 12 theme oligosaccharide 242:256 arg1 contents 258:265 oligosaccharide contents 242:265 oligosaccharide contents of glycoproteins 242:282 Endo-β-N-acetylglucosaminidase (ENGase), which catalyzes hydrolysis of N-linked oligosaccharides, is a useful tool for analyzing oligosaccharide contents of glycoproteins. 26197478 8 13 theme wild-type 1329:1337 arg1 Endo-CC1 1339:1346 the wild-type Endo-CC1 1325:1346 the wild-type Endo-CC1 1325:1346 Examination of the transglycosylation activity of Endo-CC1 revealed that the wild-type Endo-CC1 could not transfer the sialobiantennary type complex oligosaccharide onto the deglycosylated RNase B. To obtain an Endo-CC1 mutant with desired transglycosylation activity, we performed mutation analysis of the active site residue Asn 180 (N180), known to be important for catalysis, by individually replacing it with the remaining 19 amino acid residues. 26197478 9 14 theme desired 1822:1828 arg1 activity 1849:1856 the desired transglycosylation activity 1818:1856 the desired transglycosylation activity 1818:1856 Transglycosylation analyses of these mutants led us to identify one mutant, namely Endo-CC1N180H, which exhibited the desired transglycosylation activity. 26197478 7 15 theme glycoproteins 1107:1119 arg1 type 1048:1051 both N-linked high-mannose type and sialobiantennary type complex oligosaccharides 1021:1102 type 1048:1051 Our results showed that Endo-CC1 acted on both N-linked high-mannose type and sialobiantennary type complex oligosaccharides of glycoproteins RNase B and human transferrin, respectively, but not on the sialotriantennary type complex oligosaccharide of glycoprotein fetuin. 26197478 7 16 theme type 1074:1077 arg1 oligosaccharides 1087:1102 both N-linked high-mannose type and sialobiantennary type complex oligosaccharides 1021:1102 oligosaccharides 1087:1102 Our results showed that Endo-CC1 acted on both N-linked high-mannose type and sialobiantennary type complex oligosaccharides of glycoproteins RNase B and human transferrin, respectively, but not on the sialotriantennary type complex oligosaccharide of glycoprotein fetuin. 26197478 0 17 theme Coprinopsis 92:102 arg1 cinerea 104:110 Coprinopsis cinerea 92:110 Coprinopsis cinerea 92:110 Transglycosylation Activity of Glycosynthase Mutants of Endo-β-N-Acetylglucosaminidase from Coprinopsis cinerea. 26197478 1 18 theme oligosaccharides 193:208 arg1 hydrolysis 170:179 hydrolysis 170:179 hydrolysis of N-linked oligosaccharides 170:208 Endo-β-N-acetylglucosaminidase (ENGase), which catalyzes hydrolysis of N-linked oligosaccharides, is a useful tool for analyzing oligosaccharide contents of glycoproteins. 26197478 8 19 theme Endo-CC1 1463:1470 arg1 mutant 1472:1477 an Endo-CC1 mutant 1460:1477 an Endo-CC1 mutant with desired transglycosylation activity 1460:1518 Examination of the transglycosylation activity of Endo-CC1 revealed that the wild-type Endo-CC1 could not transfer the sialobiantennary type complex oligosaccharide onto the deglycosylated RNase B. To obtain an Endo-CC1 mutant with desired transglycosylation activity, we performed mutation analysis of the active site residue Asn 180 (N180), known to be important for catalysis, by individually replacing it with the remaining 19 amino acid residues. 26197478 7 20 theme high-mannose 1035:1046 arg1 type 1048:1051 both N-linked high-mannose type and sialobiantennary type complex oligosaccharides 1021:1102 type 1048:1051 Our results showed that Endo-CC1 acted on both N-linked high-mannose type and sialobiantennary type complex oligosaccharides of glycoproteins RNase B and human transferrin, respectively, but not on the sialotriantennary type complex oligosaccharide of glycoprotein fetuin. 26197478 8 21 theme transglycosylation 1492:1509 arg1 activity 1511:1518 desired transglycosylation activity 1484:1518 desired transglycosylation activity 1484:1518 Examination of the transglycosylation activity of Endo-CC1 revealed that the wild-type Endo-CC1 could not transfer the sialobiantennary type complex oligosaccharide onto the deglycosylated RNase B. To obtain an Endo-CC1 mutant with desired transglycosylation activity, we performed mutation analysis of the active site residue Asn 180 (N180), known to be important for catalysis, by individually replacing it with the remaining 19 amino acid residues. 26197478 0 22 from Mutants 45:51 arg1 cinerea 104:110 Coprinopsis cinerea 92:110 Coprinopsis cinerea 92:110 Transglycosylation Activity of Glycosynthase Mutants of Endo-β-N-Acetylglucosaminidase from Coprinopsis cinerea. 26197478 0 23 theme Transglycosylation 0:17 arg1 Activity 19:26 Transglycosylation Activity 0:26 Transglycosylation Activity of Glycosynthase Mutants of Endo-β-N-Acetylglucosaminidase from Coprinopsis cinerea. 0:111 Transglycosylation Activity of Glycosynthase Mutants of Endo-β-N-Acetylglucosaminidase from Coprinopsis cinerea. 26197478 10 24 from oligosaccharides 1951:1966 arg1 glycoproteins 1971:1983 glycoproteins 1971:1983 glycoproteins 1971:1983 Taken together, we suggest that Endo-CC1 would potentially be a valuable tool for analyzing oligosaccharides on glycoproteins, as large quantities of it could be made available more easily and less expensively than the currently used enzyme, Endo-M. 26197478 8 25 theme remaining 1670:1678 arg1 residues 1694:1701 the remaining 19 amino acid residues 1666:1701 the remaining 19 amino acid residues 1666:1701 Examination of the transglycosylation activity of Endo-CC1 revealed that the wild-type Endo-CC1 could not transfer the sialobiantennary type complex oligosaccharide onto the deglycosylated RNase B. To obtain an Endo-CC1 mutant with desired transglycosylation activity, we performed mutation analysis of the active site residue Asn 180 (N180), known to be important for catalysis, by individually replacing it with the remaining 19 amino acid residues. 26197478 1 26 link N-linked 184:191 arg1 oligosaccharides 193:208 N-linked oligosaccharides 184:208 N-linked oligosaccharides 184:208 Endo-β-N-acetylglucosaminidase (ENGase), which catalyzes hydrolysis of N-linked oligosaccharides, is a useful tool for analyzing oligosaccharide contents of glycoproteins. 26197478 10 27 theme large 1989:1993 arg1 quantities 1995:2004 large quantities 1989:2004 large quantities of it 1989:2010 Taken together, we suggest that Endo-CC1 would potentially be a valuable tool for analyzing oligosaccharides on glycoproteins, as large quantities of it could be made available more easily and less expensively than the currently used enzyme, Endo-M. 26197478 0 28 theme Mutants 45:51 arg1 Activity 19:26 Transglycosylation Activity 0:26 Transglycosylation Activity of Glycosynthase Mutants of Endo-β-N-Acetylglucosaminidase from Coprinopsis cinerea. 0:111 Transglycosylation Activity of Glycosynthase Mutants of Endo-β-N-Acetylglucosaminidase from Coprinopsis cinerea. 26197478 7 29 gly glycoproteins 1107:1119 arg1 B 1127:1127 RNase B 1121:1127 RNase B 1121:1127 Our results showed that Endo-CC1 acted on both N-linked high-mannose type and sialobiantennary type complex oligosaccharides of glycoproteins RNase B and human transferrin, respectively, but not on the sialotriantennary type complex oligosaccharide of glycoprotein fetuin. 26197478 7 29 gly glycoproteins 1107:1119 arg1 transferrin 1139:1149 human transferrin 1133:1149 human transferrin 1133:1149 Our results showed that Endo-CC1 acted on both N-linked high-mannose type and sialobiantennary type complex oligosaccharides of glycoproteins RNase B and human transferrin, respectively, but not on the sialotriantennary type complex oligosaccharide of glycoprotein fetuin. 26197478 7 29 gly glycoproteins 1107:1119 arg1 glycoproteins 1107:1119 glycoproteins RNase B and human transferrin 1107:1149 glycoproteins RNase B and human transferrin 1107:1149 Our results showed that Endo-CC1 acted on both N-linked high-mannose type and sialobiantennary type complex oligosaccharides of glycoproteins RNase B and human transferrin, respectively, but not on the sialotriantennary type complex oligosaccharide of glycoprotein fetuin. 26197478 2 30 theme type 379:382 arg1 oligosaccharides 384:399 human complex type oligosaccharides 365:399 human complex type oligosaccharides 365:399 However, there are only a few known ENGases that can catalyze the hydrolysis of human complex type oligosaccharides, and although commercially available, they are expensive. 26197478 7 31 theme fetuin 1244:1249 arg1 oligosaccharide 1212:1226 the sialotriantennary type complex oligosaccharide 1177:1226 the sialotriantennary type complex oligosaccharide of glycoprotein fetuin 1177:1249 Our results showed that Endo-CC1 acted on both N-linked high-mannose type and sialobiantennary type complex oligosaccharides of glycoproteins RNase B and human transferrin, respectively, but not on the sialotriantennary type complex oligosaccharide of glycoprotein fetuin. 26197478 8 32 theme site 1566:1569 arg1 Asn 1579:1581 the active site residue Asn 180 (N180), known to be important for catalysis, 1555:1630 Asn 1579:1581 Examination of the transglycosylation activity of Endo-CC1 revealed that the wild-type Endo-CC1 could not transfer the sialobiantennary type complex oligosaccharide onto the deglycosylated RNase B. To obtain an Endo-CC1 mutant with desired transglycosylation activity, we performed mutation analysis of the active site residue Asn 180 (N180), known to be important for catalysis, by individually replacing it with the remaining 19 amino acid residues. 26197478 3 33 theme encoding 501:508 arg1 Endo-CC2 580:587 Endo-CC2 580:587 Endo-CC2 580:587 Here, we report the cloning of two ENGase encoding cDNAs from the basidiomycete fungus Coprinopsis cinerea, Endo-CC1 and Endo-CC2. 26197478 3 33 theme encoding 501:508 arg1 cDNAs 510:514 two ENGase encoding cDNAs 490:514 two ENGase encoding cDNAs from the basidiomycete fungus Coprinopsis cinerea 490:564 Here, we report the cloning of two ENGase encoding cDNAs from the basidiomycete fungus Coprinopsis cinerea, Endo-CC1 and Endo-CC2. 26197478 3 33 theme encoding 501:508 arg1 Endo-CC1 567:574 Endo-CC1 567:574 Endo-CC1 567:574 Here, we report the cloning of two ENGase encoding cDNAs from the basidiomycete fungus Coprinopsis cinerea, Endo-CC1 and Endo-CC2. 26197478 1 34 theme glycoproteins 270:282 arg1 contents 258:265 oligosaccharide contents 242:265 oligosaccharide contents of glycoproteins 242:282 Endo-β-N-acetylglucosaminidase (ENGase), which catalyzes hydrolysis of N-linked oligosaccharides, is a useful tool for analyzing oligosaccharide contents of glycoproteins. 26197478 9 35 gly Transglycosylation 1704:1721 arg1 mutants 1741:1747 these mutants 1735:1747 these mutants 1735:1747 Transglycosylation analyses of these mutants led us to identify one mutant, namely Endo-CC1N180H, which exhibited the desired transglycosylation activity. 26197478 8 36 theme Asn 1579:1581 arg1 analysis 1543:1550 mutation analysis 1534:1550 mutation analysis of the active site residue Asn 180 (N180), known to be important for catalysis, 1534:1630 Examination of the transglycosylation activity of Endo-CC1 revealed that the wild-type Endo-CC1 could not transfer the sialobiantennary type complex oligosaccharide onto the deglycosylated RNase B. To obtain an Endo-CC1 mutant with desired transglycosylation activity, we performed mutation analysis of the active site residue Asn 180 (N180), known to be important for catalysis, by individually replacing it with the remaining 19 amino acid residues. 26197478 3 37 theme Coprinopsis 546:556 arg1 cinerea 558:564 the basidiomycete fungus Coprinopsis cinerea 521:564 the basidiomycete fungus Coprinopsis cinerea 521:564 Here, we report the cloning of two ENGase encoding cDNAs from the basidiomycete fungus Coprinopsis cinerea, Endo-CC1 and Endo-CC2. 26197478 8 38 theme amino 1683:1687 arg1 residues 1694:1701 the remaining 19 amino acid residues 1666:1701 the remaining 19 amino acid residues 1666:1701 Examination of the transglycosylation activity of Endo-CC1 revealed that the wild-type Endo-CC1 could not transfer the sialobiantennary type complex oligosaccharide onto the deglycosylated RNase B. To obtain an Endo-CC1 mutant with desired transglycosylation activity, we performed mutation analysis of the active site residue Asn 180 (N180), known to be important for catalysis, by individually replacing it with the remaining 19 amino acid residues. 26197478 3 39 theme basidiomycete 525:537 arg1 cinerea 558:564 the basidiomycete fungus Coprinopsis cinerea 521:564 the basidiomycete fungus Coprinopsis cinerea 521:564 Here, we report the cloning of two ENGase encoding cDNAs from the basidiomycete fungus Coprinopsis cinerea, Endo-CC1 and Endo-CC2. 26197478 4 40 theme recombinant 616:626 arg1 Endo-CC1 640:647 recombinant His6-tagged Endo-CC1 616:647 recombinant His6-tagged Endo-CC1 616:647 We successfully expressed recombinant His6-tagged Endo-CC1 and Endo-CC2 in Escherichia coli and purified them for enzymatic characterization. 26197478 6 41 from Endo-CC1 959:966 arg1 detail 971:976 detail 971:976 detail 971:976 Since Endo-CC1 could be prepared more easily than Endo-CC2 from E. coli cultures, we examined the enzymatic properties of Endo-CC1 in detail. 26197478 7 42 theme type 1199:1202 arg1 oligosaccharide 1212:1226 the sialotriantennary type complex oligosaccharide 1177:1226 the sialotriantennary type complex oligosaccharide of glycoprotein fetuin 1177:1249 Our results showed that Endo-CC1 acted on both N-linked high-mannose type and sialobiantennary type complex oligosaccharides of glycoproteins RNase B and human transferrin, respectively, but not on the sialotriantennary type complex oligosaccharide of glycoprotein fetuin. 26197478 6 43 from detail 971:976 arg1 properties 945:954 the enzymatic properties 931:954 the enzymatic properties of Endo-CC1 in detail 931:976 Since Endo-CC1 could be prepared more easily than Endo-CC2 from E. coli cultures, we examined the enzymatic properties of Endo-CC1 in detail. 26197478 3 44 from cinerea 558:564 arg1 Endo-CC2 580:587 Endo-CC2 580:587 Endo-CC2 580:587 Here, we report the cloning of two ENGase encoding cDNAs from the basidiomycete fungus Coprinopsis cinerea, Endo-CC1 and Endo-CC2. 26197478 3 44 from cinerea 558:564 arg1 cDNAs 510:514 two ENGase encoding cDNAs 490:514 two ENGase encoding cDNAs from the basidiomycete fungus Coprinopsis cinerea 490:564 Here, we report the cloning of two ENGase encoding cDNAs from the basidiomycete fungus Coprinopsis cinerea, Endo-CC1 and Endo-CC2. 26197478 3 44 from cinerea 558:564 arg1 cloning 479:485 the cloning 475:485 the cloning of two ENGase encoding cDNAs from the basidiomycete fungus Coprinopsis cinerea, Endo-CC1 and Endo-CC2 475:587 Here, we report the cloning of two ENGase encoding cDNAs from the basidiomycete fungus Coprinopsis cinerea, Endo-CC1 and Endo-CC2. 26197478 3 44 from cinerea 558:564 arg1 Endo-CC1 567:574 Endo-CC1 567:574 Endo-CC1 567:574 Here, we report the cloning of two ENGase encoding cDNAs from the basidiomycete fungus Coprinopsis cinerea, Endo-CC1 and Endo-CC2. 26197478 2 45 theme known 315:319 arg1 ENGases 321:327 only a few known ENGases 304:327 only a few known ENGases that can catalyze the hydrolysis of human complex type oligosaccharides 304:399 However, there are only a few known ENGases that can catalyze the hydrolysis of human complex type oligosaccharides, and although commercially available, they are expensive. 26197478 8 46 theme transglycosylation 1271:1288 arg1 activity 1290:1297 the transglycosylation activity 1267:1297 the transglycosylation activity of Endo-CC1 1267:1309 Examination of the transglycosylation activity of Endo-CC1 revealed that the wild-type Endo-CC1 could not transfer the sialobiantennary type complex oligosaccharide onto the deglycosylated RNase B. To obtain an Endo-CC1 mutant with desired transglycosylation activity, we performed mutation analysis of the active site residue Asn 180 (N180), known to be important for catalysis, by individually replacing it with the remaining 19 amino acid residues. 26197478 6 47 theme Endo-CC1 959:966 arg1 properties 945:954 the enzymatic properties 931:954 the enzymatic properties of Endo-CC1 in detail 931:976 Since Endo-CC1 could be prepared more easily than Endo-CC2 from E. coli cultures, we examined the enzymatic properties of Endo-CC1 in detail. 26197478 4 48 theme enzymatic 704:712 arg1 characterization 714:729 enzymatic characterization 704:729 enzymatic characterization 704:729 We successfully expressed recombinant His6-tagged Endo-CC1 and Endo-CC2 in Escherichia coli and purified them for enzymatic characterization. 26197478 0 49 theme Endo-β-N-Acetylglucosaminidase 56:85 arg1 Mutants 45:51 Glycosynthase Mutants 31:51 Glycosynthase Mutants of Endo-β-N-Acetylglucosaminidase from Coprinopsis cinerea 31:110 Transglycosylation Activity of Glycosynthase Mutants of Endo-β-N-Acetylglucosaminidase from Coprinopsis cinerea. 26197478 6 50 from properties 945:954 arg1 detail 971:976 detail 971:976 detail 971:976 Since Endo-CC1 could be prepared more easily than Endo-CC2 from E. coli cultures, we examined the enzymatic properties of Endo-CC1 in detail. 26197478 10 51 theme used 2088:2091 arg1 Endo-M 2101:2106 Endo-M 2101:2106 Endo-M 2101:2106 Taken together, we suggest that Endo-CC1 would potentially be a valuable tool for analyzing oligosaccharides on glycoproteins, as large quantities of it could be made available more easily and less expensively than the currently used enzyme, Endo-M. 26197478 10 51 theme used 2088:2091 arg1 enzyme 2093:2098 the currently used enzyme 2074:2098 the currently used enzyme 2074:2098 Taken together, we suggest that Endo-CC1 would potentially be a valuable tool for analyzing oligosaccharides on glycoproteins, as large quantities of it could be made available more easily and less expensively than the currently used enzyme, Endo-M. 26197478 5 52 theme hydrolytic 766:775 arg1 activity 777:784 hydrolytic activity 766:784 hydrolytic activity on high-mannose and complex type oligosaccharides 766:834 Both Endo-CC1 and Endo-CC2 showed hydrolytic activity on high-mannose and complex type oligosaccharides. 26197478 6 53 dep E. 901:902 arg1 coli 904:907 coli 904:907 coli 904:907 Since Endo-CC1 could be prepared more easily than Endo-CC2 from E. coli cultures, we examined the enzymatic properties of Endo-CC1 in detail. 26197478 8 54 theme type 1388:1391 arg1 oligosaccharide 1401:1415 the sialobiantennary type complex oligosaccharide 1367:1415 the sialobiantennary type complex oligosaccharide 1367:1415 Examination of the transglycosylation activity of Endo-CC1 revealed that the wild-type Endo-CC1 could not transfer the sialobiantennary type complex oligosaccharide onto the deglycosylated RNase B. To obtain an Endo-CC1 mutant with desired transglycosylation activity, we performed mutation analysis of the active site residue Asn 180 (N180), known to be important for catalysis, by individually replacing it with the remaining 19 amino acid residues. 26197478 9 55 theme transglycosylation 1830:1847 arg1 activity 1849:1856 the desired transglycosylation activity 1818:1856 the desired transglycosylation activity 1818:1856 Transglycosylation analyses of these mutants led us to identify one mutant, namely Endo-CC1N180H, which exhibited the desired transglycosylation activity. 26197478 0 56 from cinerea 104:110 arg1 Endo-β-N-Acetylglucosaminidase 56:85 Endo-β-N-Acetylglucosaminidase 56:85 Endo-β-N-Acetylglucosaminidase from Coprinopsis cinerea 56:110 Transglycosylation Activity of Glycosynthase Mutants of Endo-β-N-Acetylglucosaminidase from Coprinopsis cinerea. 26197478 0 56 from cinerea 104:110 arg1 Mutants 45:51 Glycosynthase Mutants 31:51 Glycosynthase Mutants of Endo-β-N-Acetylglucosaminidase from Coprinopsis cinerea 31:110 Transglycosylation Activity of Glycosynthase Mutants of Endo-β-N-Acetylglucosaminidase from Coprinopsis cinerea. 26197478 7 57 theme human 1133:1137 arg1 transferrin 1139:1149 human transferrin 1133:1149 human transferrin 1133:1149 Our results showed that Endo-CC1 acted on both N-linked high-mannose type and sialobiantennary type complex oligosaccharides of glycoproteins RNase B and human transferrin, respectively, but not on the sialotriantennary type complex oligosaccharide of glycoprotein fetuin. 26197478 7 57 theme human 1133:1137 arg1 glycoproteins 1107:1119 glycoproteins RNase B and human transferrin 1107:1149 glycoproteins RNase B and human transferrin 1107:1149 Our results showed that Endo-CC1 acted on both N-linked high-mannose type and sialobiantennary type complex oligosaccharides of glycoproteins RNase B and human transferrin, respectively, but not on the sialotriantennary type complex oligosaccharide of glycoprotein fetuin. 26197478 10 58 theme valuable 1923:1930 arg1 tool 1932:1935 a valuable tool 1921:1935 a valuable tool for analyzing oligosaccharides on glycoproteins 1921:1983 Taken together, we suggest that Endo-CC1 would potentially be a valuable tool for analyzing oligosaccharides on glycoproteins, as large quantities of it could be made available more easily and less expensively than the currently used enzyme, Endo-M. 26197478 10 58 theme valuable 1923:1930 arg1 Endo-CC1 1891:1898 Endo-CC1 1891:1898 Endo-CC1 1891:1898 Taken together, we suggest that Endo-CC1 would potentially be a valuable tool for analyzing oligosaccharides on glycoproteins, as large quantities of it could be made available more easily and less expensively than the currently used enzyme, Endo-M. 26197478 7 59 theme RNase 1121:1125 arg1 B 1127:1127 RNase B 1121:1127 RNase B 1121:1127 Our results showed that Endo-CC1 acted on both N-linked high-mannose type and sialobiantennary type complex oligosaccharides of glycoproteins RNase B and human transferrin, respectively, but not on the sialotriantennary type complex oligosaccharide of glycoprotein fetuin. 26197478 7 59 theme RNase 1121:1125 arg1 glycoproteins 1107:1119 glycoproteins RNase B and human transferrin 1107:1149 glycoproteins RNase B and human transferrin 1107:1149 Our results showed that Endo-CC1 acted on both N-linked high-mannose type and sialobiantennary type complex oligosaccharides of glycoproteins RNase B and human transferrin, respectively, but not on the sialotriantennary type complex oligosaccharide of glycoprotein fetuin. 26197478 8 60 dep B. 1447:1448 arg1 performed 1524:1532 performed 1524:1532 performed mutation analysis of the active site residue Asn 180 (N180), known to be important for catalysis, by individually replacing it with the remaining 19 amino acid residues 1524:1701 Examination of the transglycosylation activity of Endo-CC1 revealed that the wild-type Endo-CC1 could not transfer the sialobiantennary type complex oligosaccharide onto the deglycosylated RNase B. To obtain an Endo-CC1 mutant with desired transglycosylation activity, we performed mutation analysis of the active site residue Asn 180 (N180), known to be important for catalysis, by individually replacing it with the remaining 19 amino acid residues. 26197478 2 61 theme human 365:369 arg1 oligosaccharides 384:399 human complex type oligosaccharides 365:399 human complex type oligosaccharides 365:399 However, there are only a few known ENGases that can catalyze the hydrolysis of human complex type oligosaccharides, and although commercially available, they are expensive. 26197478 7 62 theme complex 1079:1085 arg1 oligosaccharides 1087:1102 both N-linked high-mannose type and sialobiantennary type complex oligosaccharides 1021:1102 oligosaccharides 1087:1102 Our results showed that Endo-CC1 acted on both N-linked high-mannose type and sialobiantennary type complex oligosaccharides of glycoproteins RNase B and human transferrin, respectively, but not on the sialotriantennary type complex oligosaccharide of glycoprotein fetuin. 26197478 1 63 theme N-linked 184:191 arg1 oligosaccharides 193:208 N-linked oligosaccharides 184:208 N-linked oligosaccharides 184:208 Endo-β-N-acetylglucosaminidase (ENGase), which catalyzes hydrolysis of N-linked oligosaccharides, is a useful tool for analyzing oligosaccharide contents of glycoproteins. 26197478 5 64 dep high-mannose 789:800 arg1 oligosaccharides 819:834 type oligosaccharides 814:834 type oligosaccharides 814:834 Both Endo-CC1 and Endo-CC2 showed hydrolytic activity on high-mannose and complex type oligosaccharides. 26197478 8 65 with mutant 1472:1477 arg1 activity 1511:1518 desired transglycosylation activity 1484:1518 desired transglycosylation activity 1484:1518 Examination of the transglycosylation activity of Endo-CC1 revealed that the wild-type Endo-CC1 could not transfer the sialobiantennary type complex oligosaccharide onto the deglycosylated RNase B. To obtain an Endo-CC1 mutant with desired transglycosylation activity, we performed mutation analysis of the active site residue Asn 180 (N180), known to be important for catalysis, by individually replacing it with the remaining 19 amino acid residues. 26197478 7 66 theme sialobiantennary 1057:1072 arg1 oligosaccharides 1087:1102 both N-linked high-mannose type and sialobiantennary type complex oligosaccharides 1021:1102 oligosaccharides 1087:1102 Our results showed that Endo-CC1 acted on both N-linked high-mannose type and sialobiantennary type complex oligosaccharides of glycoproteins RNase B and human transferrin, respectively, but not on the sialotriantennary type complex oligosaccharide of glycoprotein fetuin. 26197478 7 67 link N-linked 1026:1033 arg1 type 1048:1051 both N-linked high-mannose type and sialobiantennary type complex oligosaccharides 1021:1102 type 1048:1051 Our results showed that Endo-CC1 acted on both N-linked high-mannose type and sialobiantennary type complex oligosaccharides of glycoproteins RNase B and human transferrin, respectively, but not on the sialotriantennary type complex oligosaccharide of glycoprotein fetuin. 26197478 1 68 gly glycoproteins 270:282 arg1 glycoproteins 270:282 glycoproteins 270:282 glycoproteins 270:282 Endo-β-N-acetylglucosaminidase (ENGase), which catalyzes hydrolysis of N-linked oligosaccharides, is a useful tool for analyzing oligosaccharide contents of glycoproteins. 26197478 5 69 theme type 814:817 arg1 oligosaccharides 819:834 type oligosaccharides 814:834 type oligosaccharides 814:834 Both Endo-CC1 and Endo-CC2 showed hydrolytic activity on high-mannose and complex type oligosaccharides. 26197478 7 70 theme N-linked 1026:1033 arg1 type 1048:1051 both N-linked high-mannose type and sialobiantennary type complex oligosaccharides 1021:1102 type 1048:1051 Our results showed that Endo-CC1 acted on both N-linked high-mannose type and sialobiantennary type complex oligosaccharides of glycoproteins RNase B and human transferrin, respectively, but not on the sialotriantennary type complex oligosaccharide of glycoprotein fetuin. 26197478 8 71 theme desired 1484:1490 arg1 activity 1511:1518 desired transglycosylation activity 1484:1518 desired transglycosylation activity 1484:1518 Examination of the transglycosylation activity of Endo-CC1 revealed that the wild-type Endo-CC1 could not transfer the sialobiantennary type complex oligosaccharide onto the deglycosylated RNase B. To obtain an Endo-CC1 mutant with desired transglycosylation activity, we performed mutation analysis of the active site residue Asn 180 (N180), known to be important for catalysis, by individually replacing it with the remaining 19 amino acid residues. 26197478 7 72 dep glycoproteins 1107:1119 arg1 B 1127:1127 RNase B 1121:1127 RNase B 1121:1127 Our results showed that Endo-CC1 acted on both N-linked high-mannose type and sialobiantennary type complex oligosaccharides of glycoproteins RNase B and human transferrin, respectively, but not on the sialotriantennary type complex oligosaccharide of glycoprotein fetuin. 26197478 7 72 dep glycoproteins 1107:1119 arg1 transferrin 1139:1149 human transferrin 1133:1149 human transferrin 1133:1149 Our results showed that Endo-CC1 acted on both N-linked high-mannose type and sialobiantennary type complex oligosaccharides of glycoproteins RNase B and human transferrin, respectively, but not on the sialotriantennary type complex oligosaccharide of glycoprotein fetuin. 26197478 7 72 dep glycoproteins 1107:1119 arg1 glycoproteins 1107:1119 glycoproteins RNase B and human transferrin 1107:1149 glycoproteins RNase B and human transferrin 1107:1149 Our results showed that Endo-CC1 acted on both N-linked high-mannose type and sialobiantennary type complex oligosaccharides of glycoproteins RNase B and human transferrin, respectively, but not on the sialotriantennary type complex oligosaccharide of glycoprotein fetuin. 26197478 0 73 theme Glycosynthase 31:43 arg1 Mutants 45:51 Glycosynthase Mutants 31:51 Glycosynthase Mutants of Endo-β-N-Acetylglucosaminidase from Coprinopsis cinerea 31:110 Transglycosylation Activity of Glycosynthase Mutants of Endo-β-N-Acetylglucosaminidase from Coprinopsis cinerea. 26197478 3 74 theme ENGase 494:499 arg1 Endo-CC2 580:587 Endo-CC2 580:587 Endo-CC2 580:587 Here, we report the cloning of two ENGase encoding cDNAs from the basidiomycete fungus Coprinopsis cinerea, Endo-CC1 and Endo-CC2. 26197478 3 74 theme ENGase 494:499 arg1 cDNAs 510:514 two ENGase encoding cDNAs 490:514 two ENGase encoding cDNAs from the basidiomycete fungus Coprinopsis cinerea 490:564 Here, we report the cloning of two ENGase encoding cDNAs from the basidiomycete fungus Coprinopsis cinerea, Endo-CC1 and Endo-CC2. 26197478 3 74 theme ENGase 494:499 arg1 Endo-CC1 567:574 Endo-CC1 567:574 Endo-CC1 567:574 Here, we report the cloning of two ENGase encoding cDNAs from the basidiomycete fungus Coprinopsis cinerea, Endo-CC1 and Endo-CC2. 26197478 6 75 theme enzymatic 935:943 arg1 properties 945:954 the enzymatic properties 931:954 the enzymatic properties of Endo-CC1 in detail 931:976 Since Endo-CC1 could be prepared more easily than Endo-CC2 from E. coli cultures, we examined the enzymatic properties of Endo-CC1 in detail. 26197478 9 76 theme Transglycosylation 1704:1721 arg1 analyses 1723:1730 Transglycosylation analyses 1704:1730 Transglycosylation analyses of these mutants 1704:1747 Transglycosylation analyses of these mutants led us to identify one mutant, namely Endo-CC1N180H, which exhibited the desired transglycosylation activity. 26197478 8 77 theme acid 1689:1692 arg1 residues 1694:1701 the remaining 19 amino acid residues 1666:1701 the remaining 19 amino acid residues 1666:1701 Examination of the transglycosylation activity of Endo-CC1 revealed that the wild-type Endo-CC1 could not transfer the sialobiantennary type complex oligosaccharide onto the deglycosylated RNase B. To obtain an Endo-CC1 mutant with desired transglycosylation activity, we performed mutation analysis of the active site residue Asn 180 (N180), known to be important for catalysis, by individually replacing it with the remaining 19 amino acid residues. 26197478 8 78 theme mutation 1534:1541 arg1 analysis 1543:1550 mutation analysis 1534:1550 mutation analysis of the active site residue Asn 180 (N180), known to be important for catalysis, 1534:1630 Examination of the transglycosylation activity of Endo-CC1 revealed that the wild-type Endo-CC1 could not transfer the sialobiantennary type complex oligosaccharide onto the deglycosylated RNase B. To obtain an Endo-CC1 mutant with desired transglycosylation activity, we performed mutation analysis of the active site residue Asn 180 (N180), known to be important for catalysis, by individually replacing it with the remaining 19 amino acid residues. 26197478 3 79 from cloning 479:485 arg1 cinerea 558:564 the basidiomycete fungus Coprinopsis cinerea 521:564 the basidiomycete fungus Coprinopsis cinerea 521:564 Here, we report the cloning of two ENGase encoding cDNAs from the basidiomycete fungus Coprinopsis cinerea, Endo-CC1 and Endo-CC2. 26197478 7 80 theme glycoprotein 1231:1242 arg1 fetuin 1244:1249 glycoprotein fetuin 1231:1249 glycoprotein fetuin 1231:1249 Our results showed that Endo-CC1 acted on both N-linked high-mannose type and sialobiantennary type complex oligosaccharides of glycoproteins RNase B and human transferrin, respectively, but not on the sialotriantennary type complex oligosaccharide of glycoprotein fetuin. 26197478 7 81 gly glycoprotein 1231:1242 arg1 glycoprotein 1231:1242 glycoprotein fetuin 1231:1249 glycoprotein fetuin 1231:1249 Our results showed that Endo-CC1 acted on both N-linked high-mannose type and sialobiantennary type complex oligosaccharides of glycoproteins RNase B and human transferrin, respectively, but not on the sialotriantennary type complex oligosaccharide of glycoprotein fetuin. 26197478 2 82 theme complex 371:377 arg1 oligosaccharides 384:399 human complex type oligosaccharides 365:399 human complex type oligosaccharides 365:399 However, there are only a few known ENGases that can catalyze the hydrolysis of human complex type oligosaccharides, and although commercially available, they are expensive. 26197478 9 83 theme mutants 1741:1747 arg1 analyses 1723:1730 Transglycosylation analyses 1704:1730 Transglycosylation analyses of these mutants 1704:1747 Transglycosylation analyses of these mutants led us to identify one mutant, namely Endo-CC1N180H, which exhibited the desired transglycosylation activity. 26197478 10 84 theme it 2009:2010 arg1 quantities 1995:2004 large quantities 1989:2004 large quantities of it 1989:2010 Taken together, we suggest that Endo-CC1 would potentially be a valuable tool for analyzing oligosaccharides on glycoproteins, as large quantities of it could be made available more easily and less expensively than the currently used enzyme, Endo-M. 26197478 8 85 theme active 1559:1564 arg1 Asn 1579:1581 the active site residue Asn 180 (N180), known to be important for catalysis, 1555:1630 Asn 1579:1581 Examination of the transglycosylation activity of Endo-CC1 revealed that the wild-type Endo-CC1 could not transfer the sialobiantennary type complex oligosaccharide onto the deglycosylated RNase B. To obtain an Endo-CC1 mutant with desired transglycosylation activity, we performed mutation analysis of the active site residue Asn 180 (N180), known to be important for catalysis, by individually replacing it with the remaining 19 amino acid residues. 26197478 3 86 theme cDNAs 510:514 arg1 cloning 479:485 the cloning 475:485 the cloning of two ENGase encoding cDNAs from the basidiomycete fungus Coprinopsis cinerea, Endo-CC1 and Endo-CC2 475:587 Here, we report the cloning of two ENGase encoding cDNAs from the basidiomycete fungus Coprinopsis cinerea, Endo-CC1 and Endo-CC2. 26197478 10 87 gly glycoproteins 1971:1983 arg1 glycoproteins 1971:1983 glycoproteins 1971:1983 glycoproteins 1971:1983 Taken together, we suggest that Endo-CC1 would potentially be a valuable tool for analyzing oligosaccharides on glycoproteins, as large quantities of it could be made available more easily and less expensively than the currently used enzyme, Endo-M. 26197478 8 88 theme residue 1571:1577 arg1 Asn 1579:1581 the active site residue Asn 180 (N180), known to be important for catalysis, 1555:1630 Asn 1579:1581 Examination of the transglycosylation activity of Endo-CC1 revealed that the wild-type Endo-CC1 could not transfer the sialobiantennary type complex oligosaccharide onto the deglycosylated RNase B. To obtain an Endo-CC1 mutant with desired transglycosylation activity, we performed mutation analysis of the active site residue Asn 180 (N180), known to be important for catalysis, by individually replacing it with the remaining 19 amino acid residues. 25790529 7 0 theme vaccine 1360:1366 arg1 development 1368:1378 AIDS vaccine development 1355:1378 AIDS vaccine development 1355:1378 CONCLUSION: The results suggest that CCR5 antagonists may be extremely efficient for AIDS treatment and R5 strains should be used as candidates for AIDS vaccine development. 25790529 5 1 from account 982:988 arg1 development 1006:1016 AIDS vaccine development 993:1016 AIDS vaccine development 993:1016 These results suggest that reducing the polymorphism, heterogeneity, and PNGSs of the 4 hypervariable regions should be taken into account in AIDS vaccine development for effectively eliciting immune response. 25790529 1 2 theme hypervariable 158:170 arg1 regions 172:178 5 hypervariable regions 156:178 its 5 hypervariable regions 152:178 BACKGROUND/AIM: To investigate polymorphism characteristics of HIV-1 gpl20 and its 5 hypervariable regions. 25790529 2 3 from characteristics 296:310 arg1 subtypes 392:399 HIV-1 subtypes 386:399 HIV-1 subtypes A 386:401 MATERIALS AND METHODS: Length polymorphism, potential number of N-linked glycosylation sites (PNGSs), and sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H were analyzed. 25790529 2 3 from characteristics 296:310 arg1 D 410:410 D 410:410 D 410:410 MATERIALS AND METHODS: Length polymorphism, potential number of N-linked glycosylation sites (PNGSs), and sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H were analyzed. 25790529 2 3 from characteristics 296:310 arg1 G 413:413 G 413:413 G 413:413 MATERIALS AND METHODS: Length polymorphism, potential number of N-linked glycosylation sites (PNGSs), and sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H were analyzed. 25790529 2 3 from characteristics 296:310 arg1 B 404:404 B 404:404 B 404:404 MATERIALS AND METHODS: Length polymorphism, potential number of N-linked glycosylation sites (PNGSs), and sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H were analyzed. 25790529 2 3 from characteristics 296:310 arg1 C 407:407 C 407:407 C 407:407 MATERIALS AND METHODS: Length polymorphism, potential number of N-linked glycosylation sites (PNGSs), and sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H were analyzed. 25790529 2 3 from characteristics 296:310 arg1 H 420:420 H 420:420 H 420:420 MATERIALS AND METHODS: Length polymorphism, potential number of N-linked glycosylation sites (PNGSs), and sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H were analyzed. 25790529 2 4 dep MATERIALS 181:189 arg1 analyzed 427:434 analyzed 427:434 were analyzed 422:434 MATERIALS AND METHODS: Length polymorphism, potential number of N-linked glycosylation sites (PNGSs), and sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H were analyzed. 25790529 3 5 with gp120 549:553 arg1 length 565:570 this length 560:570 this length 560:570 RESULTS: We found that the majority of HIV-1 gpl20s have 496-515 amino acids and 21-30 PNGSs, suggesting that a gp120 with this length might be a good virus candidate for vaccine development. 25790529 5 6 theme hypervariable 939:951 arg1 regions 953:959 the 4 hypervariable regions 933:959 the 4 hypervariable regions 933:959 These results suggest that reducing the polymorphism, heterogeneity, and PNGSs of the 4 hypervariable regions should be taken into account in AIDS vaccine development for effectively eliciting immune response. 25790529 1 7 theme regions 172:178 arg1 characteristics 117:131 polymorphism characteristics 104:131 polymorphism characteristics of HIV-1 gpl20 and its 5 hypervariable regions 104:178 BACKGROUND/AIM: To investigate polymorphism characteristics of HIV-1 gpl20 and its 5 hypervariable regions. 25790529 7 8 theme CCR5 1244:1247 arg1 antagonists 1249:1259 CCR5 antagonists 1244:1259 CCR5 antagonists 1244:1259 CONCLUSION: The results suggest that CCR5 antagonists may be extremely efficient for AIDS treatment and R5 strains should be used as candidates for AIDS vaccine development. 25790529 2 9 theme sequence 287:294 arg1 characteristics 296:310 sequence characteristics 287:310 sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H 287:420 MATERIALS AND METHODS: Length polymorphism, potential number of N-linked glycosylation sites (PNGSs), and sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H were analyzed. 25790529 4 10 theme more 839:842 arg1 PNGSs 844:848 more PNGSs 839:848 more PNGSs 839:848 Among 5 hypervariable regions, the V3 regions had the lowest levels of length polymorphism and heterogeneity and less PNGSs, while V1 and V4 regions had high levels of length polymorphism and heterogeneity and more PNGSs. 25790529 3 11 theme gpl20s 482:487 arg1 majority 464:471 the majority 460:471 the majority of HIV-1 gpl20s 460:487 RESULTS: We found that the majority of HIV-1 gpl20s have 496-515 amino acids and 21-30 PNGSs, suggesting that a gp120 with this length might be a good virus candidate for vaccine development. 25790529 2 12 from number 235:240 arg1 subtypes 392:399 HIV-1 subtypes 386:399 HIV-1 subtypes A 386:401 MATERIALS AND METHODS: Length polymorphism, potential number of N-linked glycosylation sites (PNGSs), and sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H were analyzed. 25790529 2 12 from number 235:240 arg1 D 410:410 D 410:410 D 410:410 MATERIALS AND METHODS: Length polymorphism, potential number of N-linked glycosylation sites (PNGSs), and sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H were analyzed. 25790529 2 12 from number 235:240 arg1 G 413:413 G 413:413 G 413:413 MATERIALS AND METHODS: Length polymorphism, potential number of N-linked glycosylation sites (PNGSs), and sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H were analyzed. 25790529 2 12 from number 235:240 arg1 B 404:404 B 404:404 B 404:404 MATERIALS AND METHODS: Length polymorphism, potential number of N-linked glycosylation sites (PNGSs), and sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H were analyzed. 25790529 2 12 from number 235:240 arg1 C 407:407 C 407:407 C 407:407 MATERIALS AND METHODS: Length polymorphism, potential number of N-linked glycosylation sites (PNGSs), and sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H were analyzed. 25790529 2 12 from number 235:240 arg1 H 420:420 H 420:420 H 420:420 MATERIALS AND METHODS: Length polymorphism, potential number of N-linked glycosylation sites (PNGSs), and sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H were analyzed. 25790529 7 13 used used 1332:1335 arg2 strains 1314:1320 R5 strains 1311:1320 R5 strains 1311:1320 CONCLUSION: The results suggest that CCR5 antagonists may be extremely efficient for AIDS treatment and R5 strains should be used as candidates for AIDS vaccine development. 25790529 7 13 used used 1332:1335 arg2 candidates 1340:1349 candidates 1340:1349 candidates for AIDS vaccine development 1340:1378 CONCLUSION: The results suggest that CCR5 antagonists may be extremely efficient for AIDS treatment and R5 strains should be used as candidates for AIDS vaccine development. 25790529 4 14 contain had 778:780 arg1 V4 767:768 V4 767:768 V4 767:768 Among 5 hypervariable regions, the V3 regions had the lowest levels of length polymorphism and heterogeneity and less PNGSs, while V1 and V4 regions had high levels of length polymorphism and heterogeneity and more PNGSs. 25790529 4 14 contain had 778:780 arg1 V1 760:761 V1 760:761 V1 760:761 Among 5 hypervariable regions, the V3 regions had the lowest levels of length polymorphism and heterogeneity and less PNGSs, while V1 and V4 regions had high levels of length polymorphism and heterogeneity and more PNGSs. 25790529 4 14 contain had 778:780 arg2 levels 787:792 high levels 782:792 high levels of length polymorphism and heterogeneity 782:833 Among 5 hypervariable regions, the V3 regions had the lowest levels of length polymorphism and heterogeneity and less PNGSs, while V1 and V4 regions had high levels of length polymorphism and heterogeneity and more PNGSs. 25790529 4 14 contain had 778:780 arg2 PNGSs 844:848 more PNGSs 839:848 more PNGSs 839:848 Among 5 hypervariable regions, the V3 regions had the lowest levels of length polymorphism and heterogeneity and less PNGSs, while V1 and V4 regions had high levels of length polymorphism and heterogeneity and more PNGSs. 25790529 4 15 theme lowest 683:688 arg1 levels 690:695 the lowest levels 679:695 the lowest levels of length polymorphism and heterogeneity and less PNGSs 679:751 Among 5 hypervariable regions, the V3 regions had the lowest levels of length polymorphism and heterogeneity and less PNGSs, while V1 and V4 regions had high levels of length polymorphism and heterogeneity and more PNGSs. 25790529 2 16 from polymorphism 211:222 arg1 subtypes 392:399 HIV-1 subtypes 386:399 HIV-1 subtypes A 386:401 MATERIALS AND METHODS: Length polymorphism, potential number of N-linked glycosylation sites (PNGSs), and sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H were analyzed. 25790529 2 16 from polymorphism 211:222 arg1 D 410:410 D 410:410 D 410:410 MATERIALS AND METHODS: Length polymorphism, potential number of N-linked glycosylation sites (PNGSs), and sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H were analyzed. 25790529 2 16 from polymorphism 211:222 arg1 G 413:413 G 413:413 G 413:413 MATERIALS AND METHODS: Length polymorphism, potential number of N-linked glycosylation sites (PNGSs), and sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H were analyzed. 25790529 2 16 from polymorphism 211:222 arg1 B 404:404 B 404:404 B 404:404 MATERIALS AND METHODS: Length polymorphism, potential number of N-linked glycosylation sites (PNGSs), and sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H were analyzed. 25790529 2 16 from polymorphism 211:222 arg1 C 407:407 C 407:407 C 407:407 MATERIALS AND METHODS: Length polymorphism, potential number of N-linked glycosylation sites (PNGSs), and sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H were analyzed. 25790529 2 16 from polymorphism 211:222 arg1 H 420:420 H 420:420 H 420:420 MATERIALS AND METHODS: Length polymorphism, potential number of N-linked glycosylation sites (PNGSs), and sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H were analyzed. 25790529 5 17 theme AIDS 993:996 arg1 development 1006:1016 AIDS vaccine development 993:1016 AIDS vaccine development 993:1016 These results suggest that reducing the polymorphism, heterogeneity, and PNGSs of the 4 hypervariable regions should be taken into account in AIDS vaccine development for effectively eliciting immune response. 25790529 4 18 theme polymorphism 707:718 arg1 levels 690:695 the lowest levels 679:695 the lowest levels of length polymorphism and heterogeneity and less PNGSs 679:751 Among 5 hypervariable regions, the V3 regions had the lowest levels of length polymorphism and heterogeneity and less PNGSs, while V1 and V4 regions had high levels of length polymorphism and heterogeneity and more PNGSs. 25790529 4 19 dep V1 760:761 arg1 regions 770:776 regions 770:776 regions 770:776 Among 5 hypervariable regions, the V3 regions had the lowest levels of length polymorphism and heterogeneity and less PNGSs, while V1 and V4 regions had high levels of length polymorphism and heterogeneity and more PNGSs. 25790529 5 20 theme vaccine 998:1004 arg1 development 1006:1016 AIDS vaccine development 993:1016 AIDS vaccine development 993:1016 These results suggest that reducing the polymorphism, heterogeneity, and PNGSs of the 4 hypervariable regions should be taken into account in AIDS vaccine development for effectively eliciting immune response. 25790529 7 21 theme AIDS 1355:1358 arg1 development 1368:1378 AIDS vaccine development 1355:1378 AIDS vaccine development 1355:1378 CONCLUSION: The results suggest that CCR5 antagonists may be extremely efficient for AIDS treatment and R5 strains should be used as candidates for AIDS vaccine development. 25790529 3 22 theme amino 502:506 arg1 acids 508:512 496-515 amino acids 494:512 496-515 amino acids 494:512 RESULTS: We found that the majority of HIV-1 gpl20s have 496-515 amino acids and 21-30 PNGSs, suggesting that a gp120 with this length might be a good virus candidate for vaccine development. 25790529 2 23 theme HIV-1 386:390 arg1 subtypes 392:399 HIV-1 subtypes 386:399 HIV-1 subtypes A 386:401 MATERIALS AND METHODS: Length polymorphism, potential number of N-linked glycosylation sites (PNGSs), and sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H were analyzed. 25790529 2 23 theme HIV-1 386:390 arg1 D 410:410 D 410:410 D 410:410 MATERIALS AND METHODS: Length polymorphism, potential number of N-linked glycosylation sites (PNGSs), and sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H were analyzed. 25790529 2 23 theme HIV-1 386:390 arg1 G 413:413 G 413:413 G 413:413 MATERIALS AND METHODS: Length polymorphism, potential number of N-linked glycosylation sites (PNGSs), and sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H were analyzed. 25790529 2 23 theme HIV-1 386:390 arg1 B 404:404 B 404:404 B 404:404 MATERIALS AND METHODS: Length polymorphism, potential number of N-linked glycosylation sites (PNGSs), and sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H were analyzed. 25790529 2 23 theme HIV-1 386:390 arg1 C 407:407 C 407:407 C 407:407 MATERIALS AND METHODS: Length polymorphism, potential number of N-linked glycosylation sites (PNGSs), and sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H were analyzed. 25790529 2 23 theme HIV-1 386:390 arg1 H 420:420 H 420:420 H 420:420 MATERIALS AND METHODS: Length polymorphism, potential number of N-linked glycosylation sites (PNGSs), and sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H were analyzed. 25790529 0 24 theme Polymorphism 0:11 arg1 characteristics 13:27 Polymorphism characteristics 0:27 Polymorphism characteristics of HIV-1 gpl20 and 5 hypervariable regions. 0:71 Polymorphism characteristics of HIV-1 gpl20 and 5 hypervariable regions. 25790529 7 25 theme R5 1311:1312 arg1 candidates 1340:1349 candidates 1340:1349 candidates for AIDS vaccine development 1340:1378 CONCLUSION: The results suggest that CCR5 antagonists may be extremely efficient for AIDS treatment and R5 strains should be used as candidates for AIDS vaccine development. 25790529 7 25 theme R5 1311:1312 arg1 strains 1314:1320 R5 strains 1311:1320 R5 strains 1311:1320 CONCLUSION: The results suggest that CCR5 antagonists may be extremely efficient for AIDS treatment and R5 strains should be used as candidates for AIDS vaccine development. 25790529 6 26 theme R5 1135:1136 arg1 tropism 1138:1144 R5 tropism 1135:1144 R5 tropism 1135:1144 Except for subtype D, other subtypes have the consensus V3 sequences with R5 tropism, implying that the majority of HIV-1 strains are R5 strains. 25790529 7 27 theme AIDS 1292:1295 arg1 treatment 1297:1305 AIDS treatment 1292:1305 AIDS treatment 1292:1305 CONCLUSION: The results suggest that CCR5 antagonists may be extremely efficient for AIDS treatment and R5 strains should be used as candidates for AIDS vaccine development. 25790529 2 28 gly glycosylation 254:266 arg2 PNGSs 275:279 PNGSs 275:279 PNGSs 275:279 MATERIALS AND METHODS: Length polymorphism, potential number of N-linked glycosylation sites (PNGSs), and sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H were analyzed. 25790529 2 28 gly glycosylation 254:266 arg2 sites 268:272 N-linked glycosylation sites 245:272 N-linked glycosylation sites (PNGSs) 245:280 MATERIALS AND METHODS: Length polymorphism, potential number of N-linked glycosylation sites (PNGSs), and sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H were analyzed. 25790529 3 29 contain have 489:492 arg2 acids 508:512 496-515 amino acids 494:512 496-515 amino acids 494:512 RESULTS: We found that the majority of HIV-1 gpl20s have 496-515 amino acids and 21-30 PNGSs, suggesting that a gp120 with this length might be a good virus candidate for vaccine development. 25790529 3 29 contain have 489:492 arg1 majority 464:471 the majority 460:471 the majority of HIV-1 gpl20s 460:487 RESULTS: We found that the majority of HIV-1 gpl20s have 496-515 amino acids and 21-30 PNGSs, suggesting that a gp120 with this length might be a good virus candidate for vaccine development. 25790529 3 29 contain have 489:492 arg2 PNGSs 524:528 21-30 PNGSs 518:528 21-30 PNGSs 518:528 RESULTS: We found that the majority of HIV-1 gpl20s have 496-515 amino acids and 21-30 PNGSs, suggesting that a gp120 with this length might be a good virus candidate for vaccine development. 25790529 6 30 theme consensus 1107:1115 arg1 sequences 1120:1128 the consensus V3 sequences 1103:1128 the consensus V3 sequences 1103:1128 Except for subtype D, other subtypes have the consensus V3 sequences with R5 tropism, implying that the majority of HIV-1 strains are R5 strains. 25790529 1 31 theme polymorphism 104:115 arg1 characteristics 117:131 polymorphism characteristics 104:131 polymorphism characteristics of HIV-1 gpl20 and its 5 hypervariable regions 104:178 BACKGROUND/AIM: To investigate polymorphism characteristics of HIV-1 gpl20 and its 5 hypervariable regions. 25790529 4 32 theme heterogeneity 724:736 arg1 levels 690:695 the lowest levels 679:695 the lowest levels of length polymorphism and heterogeneity and less PNGSs 679:751 Among 5 hypervariable regions, the V3 regions had the lowest levels of length polymorphism and heterogeneity and less PNGSs, while V1 and V4 regions had high levels of length polymorphism and heterogeneity and more PNGSs. 25790529 4 33 theme length 700:705 arg1 polymorphism 707:718 length polymorphism 700:718 length polymorphism 700:718 Among 5 hypervariable regions, the V3 regions had the lowest levels of length polymorphism and heterogeneity and less PNGSs, while V1 and V4 regions had high levels of length polymorphism and heterogeneity and more PNGSs. 25790529 4 34 theme polymorphism 804:815 arg1 levels 787:792 high levels 782:792 high levels of length polymorphism and heterogeneity 782:833 Among 5 hypervariable regions, the V3 regions had the lowest levels of length polymorphism and heterogeneity and less PNGSs, while V1 and V4 regions had high levels of length polymorphism and heterogeneity and more PNGSs. 25790529 4 34 theme polymorphism 804:815 arg1 PNGSs 844:848 more PNGSs 839:848 more PNGSs 839:848 Among 5 hypervariable regions, the V3 regions had the lowest levels of length polymorphism and heterogeneity and less PNGSs, while V1 and V4 regions had high levels of length polymorphism and heterogeneity and more PNGSs. 25790529 5 35 gly heterogeneity 905:917 arg1 regions 953:959 the 4 hypervariable regions 933:959 the 4 hypervariable regions 933:959 These results suggest that reducing the polymorphism, heterogeneity, and PNGSs of the 4 hypervariable regions should be taken into account in AIDS vaccine development for effectively eliciting immune response. 25790529 2 36 theme gp120 343:347 arg1 polymorphism 211:222 Length polymorphism 204:222 Length polymorphism 204:222 MATERIALS AND METHODS: Length polymorphism, potential number of N-linked glycosylation sites (PNGSs), and sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H were analyzed. 25790529 2 36 theme gp120 343:347 arg1 number 235:240 potential number 225:240 potential number of N-linked glycosylation sites (PNGSs) 225:280 MATERIALS AND METHODS: Length polymorphism, potential number of N-linked glycosylation sites (PNGSs), and sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H were analyzed. 25790529 2 36 theme gp120 343:347 arg1 characteristics 296:310 sequence characteristics 287:310 sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H 287:420 MATERIALS AND METHODS: Length polymorphism, potential number of N-linked glycosylation sites (PNGSs), and sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H were analyzed. 25790529 2 37 theme N-linked 245:252 arg1 sites 268:272 N-linked glycosylation sites 245:272 N-linked glycosylation sites (PNGSs) 245:280 MATERIALS AND METHODS: Length polymorphism, potential number of N-linked glycosylation sites (PNGSs), and sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H were analyzed. 25790529 2 37 theme N-linked 245:252 arg1 PNGSs 275:279 PNGSs 275:279 PNGSs 275:279 MATERIALS AND METHODS: Length polymorphism, potential number of N-linked glycosylation sites (PNGSs), and sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H were analyzed. 25790529 6 38 theme other 1083:1087 arg1 subtypes 1089:1096 other subtypes 1083:1096 other subtypes 1083:1096 Except for subtype D, other subtypes have the consensus V3 sequences with R5 tropism, implying that the majority of HIV-1 strains are R5 strains. 25790529 0 39 theme gpl20 38:42 arg1 characteristics 13:27 Polymorphism characteristics 0:27 Polymorphism characteristics of HIV-1 gpl20 and 5 hypervariable regions. 0:71 Polymorphism characteristics of HIV-1 gpl20 and 5 hypervariable regions. 25790529 5 40 theme immune 1044:1049 arg1 response 1051:1058 immune response 1044:1058 immune response 1044:1058 These results suggest that reducing the polymorphism, heterogeneity, and PNGSs of the 4 hypervariable regions should be taken into account in AIDS vaccine development for effectively eliciting immune response. 25790529 4 41 theme heterogeneity 821:833 arg1 levels 787:792 high levels 782:792 high levels of length polymorphism and heterogeneity 782:833 Among 5 hypervariable regions, the V3 regions had the lowest levels of length polymorphism and heterogeneity and less PNGSs, while V1 and V4 regions had high levels of length polymorphism and heterogeneity and more PNGSs. 25790529 4 41 theme heterogeneity 821:833 arg1 PNGSs 844:848 more PNGSs 839:848 more PNGSs 839:848 Among 5 hypervariable regions, the V3 regions had the lowest levels of length polymorphism and heterogeneity and less PNGSs, while V1 and V4 regions had high levels of length polymorphism and heterogeneity and more PNGSs. 25790529 0 42 theme HIV-1 32:36 arg1 gpl20 38:42 HIV-1 gpl20 32:42 HIV-1 gpl20 32:42 Polymorphism characteristics of HIV-1 gpl20 and 5 hypervariable regions. 25790529 4 43 contain had 675:677 arg2 levels 690:695 the lowest levels 679:695 the lowest levels of length polymorphism and heterogeneity and less PNGSs 679:751 Among 5 hypervariable regions, the V3 regions had the lowest levels of length polymorphism and heterogeneity and less PNGSs, while V1 and V4 regions had high levels of length polymorphism and heterogeneity and more PNGSs. 25790529 4 43 contain had 675:677 arg1 regions 667:673 the V3 regions 660:673 the V3 regions 660:673 Among 5 hypervariable regions, the V3 regions had the lowest levels of length polymorphism and heterogeneity and less PNGSs, while V1 and V4 regions had high levels of length polymorphism and heterogeneity and more PNGSs. 25790529 0 44 theme hypervariable 50:62 arg1 regions 64:70 5 hypervariable regions 48:70 5 hypervariable regions 48:70 Polymorphism characteristics of HIV-1 gpl20 and 5 hypervariable regions. 25790529 6 45 theme R5 1195:1196 arg1 majority 1165:1172 the majority 1161:1172 the majority of HIV-1 strains 1161:1189 Except for subtype D, other subtypes have the consensus V3 sequences with R5 tropism, implying that the majority of HIV-1 strains are R5 strains. 25790529 6 45 theme R5 1195:1196 arg1 strains 1198:1204 R5 strains 1195:1204 R5 strains 1195:1204 Except for subtype D, other subtypes have the consensus V3 sequences with R5 tropism, implying that the majority of HIV-1 strains are R5 strains. 25790529 6 46 theme V3 1117:1118 arg1 sequences 1120:1128 the consensus V3 sequences 1103:1128 the consensus V3 sequences 1103:1128 Except for subtype D, other subtypes have the consensus V3 sequences with R5 tropism, implying that the majority of HIV-1 strains are R5 strains. 25790529 6 47 theme strains 1183:1189 arg1 majority 1165:1172 the majority 1161:1172 the majority of HIV-1 strains 1161:1189 Except for subtype D, other subtypes have the consensus V3 sequences with R5 tropism, implying that the majority of HIV-1 strains are R5 strains. 25790529 6 47 theme strains 1183:1189 arg1 strains 1198:1204 R5 strains 1195:1204 R5 strains 1195:1204 Except for subtype D, other subtypes have the consensus V3 sequences with R5 tropism, implying that the majority of HIV-1 strains are R5 strains. 25790529 6 48 contain have 1098:1101 arg2 sequences 1120:1128 the consensus V3 sequences 1103:1128 the consensus V3 sequences 1103:1128 Except for subtype D, other subtypes have the consensus V3 sequences with R5 tropism, implying that the majority of HIV-1 strains are R5 strains. 25790529 6 48 contain have 1098:1101 arg1 subtypes 1089:1096 other subtypes 1083:1096 other subtypes 1083:1096 Except for subtype D, other subtypes have the consensus V3 sequences with R5 tropism, implying that the majority of HIV-1 strains are R5 strains. 25790529 4 49 theme high 782:785 arg1 levels 787:792 high levels 782:792 high levels of length polymorphism and heterogeneity 782:833 Among 5 hypervariable regions, the V3 regions had the lowest levels of length polymorphism and heterogeneity and less PNGSs, while V1 and V4 regions had high levels of length polymorphism and heterogeneity and more PNGSs. 25790529 3 50 theme good 583:586 arg1 candidate 594:602 a good virus candidate 581:602 a good virus candidate for vaccine development 581:626 RESULTS: We found that the majority of HIV-1 gpl20s have 496-515 amino acids and 21-30 PNGSs, suggesting that a gp120 with this length might be a good virus candidate for vaccine development. 25790529 3 50 theme good 583:586 arg1 gp120 549:553 a gp120 547:553 a gp120 with this length 547:570 RESULTS: We found that the majority of HIV-1 gpl20s have 496-515 amino acids and 21-30 PNGSs, suggesting that a gp120 with this length might be a good virus candidate for vaccine development. 25790529 2 51 theme potential 225:233 arg1 number 235:240 potential number 225:240 potential number of N-linked glycosylation sites (PNGSs) 225:280 MATERIALS AND METHODS: Length polymorphism, potential number of N-linked glycosylation sites (PNGSs), and sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H were analyzed. 25790529 1 52 theme HIV-1 136:140 arg1 gpl20 142:146 HIV-1 gpl20 136:146 HIV-1 gpl20 136:146 BACKGROUND/AIM: To investigate polymorphism characteristics of HIV-1 gpl20 and its 5 hypervariable regions. 25790529 4 53 theme hypervariable 637:649 arg1 regions 651:657 5 hypervariable regions 635:657 5 hypervariable regions 635:657 Among 5 hypervariable regions, the V3 regions had the lowest levels of length polymorphism and heterogeneity and less PNGSs, while V1 and V4 regions had high levels of length polymorphism and heterogeneity and more PNGSs. 25790529 2 54 dep subtypes 392:399 arg1 A 401:401 A 401:401 A 401:401 MATERIALS AND METHODS: Length polymorphism, potential number of N-linked glycosylation sites (PNGSs), and sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H were analyzed. 25790529 4 55 theme length 797:802 arg1 polymorphism 804:815 length polymorphism 797:815 length polymorphism 797:815 Among 5 hypervariable regions, the V3 regions had the lowest levels of length polymorphism and heterogeneity and less PNGSs, while V1 and V4 regions had high levels of length polymorphism and heterogeneity and more PNGSs. 25790529 3 56 theme virus 588:592 arg1 candidate 594:602 a good virus candidate 581:602 a good virus candidate for vaccine development 581:626 RESULTS: We found that the majority of HIV-1 gpl20s have 496-515 amino acids and 21-30 PNGSs, suggesting that a gp120 with this length might be a good virus candidate for vaccine development. 25790529 3 56 theme virus 588:592 arg1 gp120 549:553 a gp120 547:553 a gp120 with this length 547:570 RESULTS: We found that the majority of HIV-1 gpl20s have 496-515 amino acids and 21-30 PNGSs, suggesting that a gp120 with this length might be a good virus candidate for vaccine development. 25790529 2 57 from subtypes 392:399 arg1 gp120 343:347 nearly all available global gp120 315:347 nearly all available global gp120 315:347 MATERIALS AND METHODS: Length polymorphism, potential number of N-linked glycosylation sites (PNGSs), and sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H were analyzed. 25790529 2 57 from subtypes 392:399 arg1 polymorphism 211:222 Length polymorphism 204:222 Length polymorphism 204:222 MATERIALS AND METHODS: Length polymorphism, potential number of N-linked glycosylation sites (PNGSs), and sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H were analyzed. 25790529 2 57 from subtypes 392:399 arg1 number 235:240 potential number 225:240 potential number of N-linked glycosylation sites (PNGSs) 225:280 MATERIALS AND METHODS: Length polymorphism, potential number of N-linked glycosylation sites (PNGSs), and sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H were analyzed. 25790529 2 57 from subtypes 392:399 arg1 characteristics 296:310 sequence characteristics 287:310 sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H 287:420 MATERIALS AND METHODS: Length polymorphism, potential number of N-linked glycosylation sites (PNGSs), and sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H were analyzed. 25790529 2 57 from subtypes 392:399 arg1 regions 373:379 5 hypervariable regions 357:379 its 5 hypervariable regions 353:379 MATERIALS AND METHODS: Length polymorphism, potential number of N-linked glycosylation sites (PNGSs), and sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H were analyzed. 25790529 1 58 theme gpl20 142:146 arg1 characteristics 117:131 polymorphism characteristics 104:131 polymorphism characteristics of HIV-1 gpl20 and its 5 hypervariable regions 104:178 BACKGROUND/AIM: To investigate polymorphism characteristics of HIV-1 gpl20 and its 5 hypervariable regions. 25790529 4 59 theme V3 664:665 arg1 regions 667:673 the V3 regions 660:673 the V3 regions 660:673 Among 5 hypervariable regions, the V3 regions had the lowest levels of length polymorphism and heterogeneity and less PNGSs, while V1 and V4 regions had high levels of length polymorphism and heterogeneity and more PNGSs. 25790529 6 60 theme HIV-1 1177:1181 arg1 strains 1183:1189 HIV-1 strains 1177:1189 HIV-1 strains 1177:1189 Except for subtype D, other subtypes have the consensus V3 sequences with R5 tropism, implying that the majority of HIV-1 strains are R5 strains. 25790529 2 61 theme Length 204:209 arg1 polymorphism 211:222 Length polymorphism 204:222 Length polymorphism 204:222 MATERIALS AND METHODS: Length polymorphism, potential number of N-linked glycosylation sites (PNGSs), and sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H were analyzed. 25790529 3 62 theme HIV-1 476:480 arg1 gpl20s 482:487 HIV-1 gpl20s 476:487 HIV-1 gpl20s 476:487 RESULTS: We found that the majority of HIV-1 gpl20s have 496-515 amino acids and 21-30 PNGSs, suggesting that a gp120 with this length might be a good virus candidate for vaccine development. 25790529 2 63 theme available 326:334 arg1 gp120 343:347 nearly all available global gp120 315:347 nearly all available global gp120 315:347 MATERIALS AND METHODS: Length polymorphism, potential number of N-linked glycosylation sites (PNGSs), and sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H were analyzed. 25790529 2 64 theme global 336:341 arg1 gp120 343:347 nearly all available global gp120 315:347 nearly all available global gp120 315:347 MATERIALS AND METHODS: Length polymorphism, potential number of N-linked glycosylation sites (PNGSs), and sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H were analyzed. 25790529 5 65 theme regions 953:959 arg1 heterogeneity 905:917 heterogeneity 905:917 heterogeneity 905:917 These results suggest that reducing the polymorphism, heterogeneity, and PNGSs of the 4 hypervariable regions should be taken into account in AIDS vaccine development for effectively eliciting immune response. 25790529 5 65 theme regions 953:959 arg1 PNGSs 924:928 PNGSs 924:928 PNGSs 924:928 These results suggest that reducing the polymorphism, heterogeneity, and PNGSs of the 4 hypervariable regions should be taken into account in AIDS vaccine development for effectively eliciting immune response. 25790529 5 65 theme regions 953:959 arg1 polymorphism 891:902 polymorphism 891:902 polymorphism 891:902 These results suggest that reducing the polymorphism, heterogeneity, and PNGSs of the 4 hypervariable regions should be taken into account in AIDS vaccine development for effectively eliciting immune response. 25790529 2 66 theme sites 268:272 arg1 polymorphism 211:222 Length polymorphism 204:222 Length polymorphism 204:222 MATERIALS AND METHODS: Length polymorphism, potential number of N-linked glycosylation sites (PNGSs), and sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H were analyzed. 25790529 2 66 theme sites 268:272 arg1 number 235:240 potential number 225:240 potential number of N-linked glycosylation sites (PNGSs) 225:280 MATERIALS AND METHODS: Length polymorphism, potential number of N-linked glycosylation sites (PNGSs), and sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H were analyzed. 25790529 2 66 theme sites 268:272 arg1 characteristics 296:310 sequence characteristics 287:310 sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H 287:420 MATERIALS AND METHODS: Length polymorphism, potential number of N-linked glycosylation sites (PNGSs), and sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H were analyzed. 25790529 2 67 theme regions 373:379 arg1 polymorphism 211:222 Length polymorphism 204:222 Length polymorphism 204:222 MATERIALS AND METHODS: Length polymorphism, potential number of N-linked glycosylation sites (PNGSs), and sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H were analyzed. 25790529 2 67 theme regions 373:379 arg1 number 235:240 potential number 225:240 potential number of N-linked glycosylation sites (PNGSs) 225:280 MATERIALS AND METHODS: Length polymorphism, potential number of N-linked glycosylation sites (PNGSs), and sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H were analyzed. 25790529 2 67 theme regions 373:379 arg1 characteristics 296:310 sequence characteristics 287:310 sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H 287:420 MATERIALS AND METHODS: Length polymorphism, potential number of N-linked glycosylation sites (PNGSs), and sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H were analyzed. 25790529 6 68 theme subtype 1072:1078 arg1 D 1080:1080 subtype D 1072:1080 subtype D 1072:1080 Except for subtype D, other subtypes have the consensus V3 sequences with R5 tropism, implying that the majority of HIV-1 strains are R5 strains. 25790529 2 69 link N-linked 245:252 arg1 sites 268:272 N-linked glycosylation sites 245:272 N-linked glycosylation sites (PNGSs) 245:280 MATERIALS AND METHODS: Length polymorphism, potential number of N-linked glycosylation sites (PNGSs), and sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H were analyzed. 25790529 2 69 link N-linked 245:252 arg1 PNGSs 275:279 PNGSs 275:279 PNGSs 275:279 MATERIALS AND METHODS: Length polymorphism, potential number of N-linked glycosylation sites (PNGSs), and sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H were analyzed. 25790529 0 70 theme regions 64:70 arg1 characteristics 13:27 Polymorphism characteristics 0:27 Polymorphism characteristics of HIV-1 gpl20 and 5 hypervariable regions. 0:71 Polymorphism characteristics of HIV-1 gpl20 and 5 hypervariable regions. 25790529 3 71 theme vaccine 608:614 arg1 development 616:626 vaccine development 608:626 vaccine development 608:626 RESULTS: We found that the majority of HIV-1 gpl20s have 496-515 amino acids and 21-30 PNGSs, suggesting that a gp120 with this length might be a good virus candidate for vaccine development. 25790529 2 72 theme glycosylation 254:266 arg1 sites 268:272 N-linked glycosylation sites 245:272 N-linked glycosylation sites (PNGSs) 245:280 MATERIALS AND METHODS: Length polymorphism, potential number of N-linked glycosylation sites (PNGSs), and sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H were analyzed. 25790529 2 72 theme glycosylation 254:266 arg1 PNGSs 275:279 PNGSs 275:279 PNGSs 275:279 MATERIALS AND METHODS: Length polymorphism, potential number of N-linked glycosylation sites (PNGSs), and sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H were analyzed. 25790529 2 73 theme hypervariable 359:371 arg1 regions 373:379 5 hypervariable regions 357:379 its 5 hypervariable regions 353:379 MATERIALS AND METHODS: Length polymorphism, potential number of N-linked glycosylation sites (PNGSs), and sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H were analyzed. 25541284 0 0 theme myelin 66:71 arg1 glycoprotein 89:100 myelin oligodendrocyte glycoprotein 66:100 myelin oligodendrocyte glycoprotein (MOG) 66:106 The role of N-glycan in folding, trafficking and pathogenicity of myelin oligodendrocyte glycoprotein (MOG). 25541284 0 0 theme myelin 66:71 arg1 MOG 103:105 MOG 103:105 MOG 103:105 The role of N-glycan in folding, trafficking and pathogenicity of myelin oligodendrocyte glycoprotein (MOG). 25541284 2 1 gly N-glycosylation 255:269 arg2 site 271:274 a single N-glycosylation site 246:274 a single N-glycosylation site within its extracellular domain 246:306 MOG has a single N-glycosylation site within its extracellular domain. 25541284 9 2 theme Issue 1088:1092 arg1 part 1070:1073 part 1070:1073 part of a Special Issue entitled: 13th European Symposium on Calcium 1070:1137 This article is part of a Special Issue entitled: 13th European Symposium on Calcium. 25541284 1 3 theme central 214:220 arg1 system 230:235 the central nervous system 210:235 the central nervous system 210:235 Myelin oligodendrocyte glycoprotein (MOG) is a type I integral membrane protein that is expressed in the central nervous system. 25541284 0 4 from role 4:7 arg1 folding 24:30 folding 24:30 folding 24:30 The role of N-glycan in folding, trafficking and pathogenicity of myelin oligodendrocyte glycoprotein (MOG). 25541284 0 4 from role 4:7 arg1 pathogenicity 49:61 pathogenicity 49:61 pathogenicity 49:61 The role of N-glycan in folding, trafficking and pathogenicity of myelin oligodendrocyte glycoprotein (MOG). 25541284 0 4 from role 4:7 arg1 trafficking 33:43 trafficking 33:43 trafficking 33:43 The role of N-glycan in folding, trafficking and pathogenicity of myelin oligodendrocyte glycoprotein (MOG). 25541284 9 5 theme entitled 1094:1101 arg1 Issue 1088:1092 a Special Issue entitled 1078:1101 a Special Issue entitled: 13th European Symposium on Calcium 1078:1137 This article is part of a Special Issue entitled: 13th European Symposium on Calcium. 25541284 7 6 theme MOG 805:807 arg1 abundance 809:817 MOG abundance 805:817 MOG abundance in the absence of endoplasmic reticulum molecular chaperone calnexin 805:886 We concluded that the lack of sugar did not impact on MOG abundance in the absence of endoplasmic reticulum molecular chaperone calnexin. 25541284 1 7 theme nervous 222:228 arg1 system 230:235 the central nervous system 210:235 the central nervous system 210:235 Myelin oligodendrocyte glycoprotein (MOG) is a type I integral membrane protein that is expressed in the central nervous system. 25541284 0 8 theme glycoprotein 89:100 arg1 folding 24:30 folding 24:30 folding 24:30 The role of N-glycan in folding, trafficking and pathogenicity of myelin oligodendrocyte glycoprotein (MOG). 25541284 0 8 theme glycoprotein 89:100 arg1 pathogenicity 49:61 pathogenicity 49:61 pathogenicity 49:61 The role of N-glycan in folding, trafficking and pathogenicity of myelin oligodendrocyte glycoprotein (MOG). 25541284 0 8 theme glycoprotein 89:100 arg1 trafficking 33:43 trafficking 33:43 trafficking 33:43 The role of N-glycan in folding, trafficking and pathogenicity of myelin oligodendrocyte glycoprotein (MOG). 25541284 4 9 theme post-translational 485:502 arg1 N-glycosylation 453:467 N-glycosylation 453:467 N-glycosylation 453:467 N-glycosylation is an important post-translational modification of protein that might impact their folding, localization and function. 25541284 4 9 theme post-translational 485:502 arg1 modification 504:515 an important post-translational modification 472:515 an important post-translational modification of protein that might impact their folding, localization and function 472:585 N-glycosylation is an important post-translational modification of protein that might impact their folding, localization and function. 25541284 5 10 theme MOG 633:635 arg1 biology 622:628 the biology 618:628 the biology of MOG 618:635 However, the role of sugar in the biology of MOG is not well understood. 25541284 9 11 theme 13th 1104:1107 arg1 Symposium 1118:1126 13th European Symposium 1104:1126 a Special Issue entitled: 13th European Symposium on Calcium 1078:1137 This article is part of a Special Issue entitled: 13th European Symposium on Calcium. 25541284 2 12 theme single 248:253 arg1 site 271:274 a single N-glycosylation site 246:274 a single N-glycosylation site within its extracellular domain 246:306 MOG has a single N-glycosylation site within its extracellular domain. 25541284 7 13 theme molecular 859:867 arg1 calnexin 879:886 endoplasmic reticulum molecular chaperone calnexin 837:886 endoplasmic reticulum molecular chaperone calnexin 837:886 We concluded that the lack of sugar did not impact on MOG abundance in the absence of endoplasmic reticulum molecular chaperone calnexin. 25541284 0 14 theme oligodendrocyte 73:87 arg1 glycoprotein 89:100 myelin oligodendrocyte glycoprotein 66:100 myelin oligodendrocyte glycoprotein (MOG) 66:106 The role of N-glycan in folding, trafficking and pathogenicity of myelin oligodendrocyte glycoprotein (MOG). 25541284 0 14 theme oligodendrocyte 73:87 arg1 MOG 103:105 MOG 103:105 MOG 103:105 The role of N-glycan in folding, trafficking and pathogenicity of myelin oligodendrocyte glycoprotein (MOG). 25541284 8 15 theme subcellular 960:970 arg1 localization 972:983 MOG's subcellular localization 954:983 MOG's subcellular localization 954:983 We also show that the absence of N-glycan did not interfere with MOG's subcellular localization and it did not result in activation of endoplasmic reticulum stress. 25541284 8 16 theme N-glycan 922:929 arg1 absence 911:917 the absence 907:917 the absence of N-glycan 907:929 We also show that the absence of N-glycan did not interfere with MOG's subcellular localization and it did not result in activation of endoplasmic reticulum stress. 25541284 7 17 from abundance 809:817 arg1 absence 826:832 the absence 822:832 the absence of endoplasmic reticulum molecular chaperone calnexin 822:886 We concluded that the lack of sugar did not impact on MOG abundance in the absence of endoplasmic reticulum molecular chaperone calnexin. 25541284 2 18 theme extracellular 287:299 arg1 domain 301:306 its extracellular domain 283:306 its extracellular domain 283:306 MOG has a single N-glycosylation site within its extracellular domain. 25541284 3 19 theme sclerosis 433:441 arg1 patients 443:450 multiple sclerosis patients 424:450 multiple sclerosis patients 424:450 MOG has been linked with pathogenesis of multiple sclerosis; anti-MOG antibodies have been detected in the sera of multiple sclerosis patients. 25541284 5 20 theme sugar 609:613 arg1 role 601:604 the role 597:604 the role of sugar in the biology of MOG 597:635 However, the role of sugar in the biology of MOG is not well understood. 25541284 7 21 theme calnexin 879:886 arg1 absence 826:832 the absence 822:832 the absence of endoplasmic reticulum molecular chaperone calnexin 822:886 We concluded that the lack of sugar did not impact on MOG abundance in the absence of endoplasmic reticulum molecular chaperone calnexin. 25541284 3 22 theme multiple 350:357 arg1 sclerosis 359:367 multiple sclerosis 350:367 multiple sclerosis 350:367 MOG has been linked with pathogenesis of multiple sclerosis; anti-MOG antibodies have been detected in the sera of multiple sclerosis patients. 25541284 9 23 dep Issue 1088:1092 arg1 Symposium 1118:1126 13th European Symposium 1104:1126 a Special Issue entitled: 13th European Symposium on Calcium 1078:1137 This article is part of a Special Issue entitled: 13th European Symposium on Calcium. 25541284 8 24 theme endoplasmic 1024:1034 arg1 reticulum 1036:1044 endoplasmic reticulum 1024:1044 endoplasmic reticulum stress 1024:1051 We also show that the absence of N-glycan did not interfere with MOG's subcellular localization and it did not result in activation of endoplasmic reticulum stress. 25541284 1 25 theme type 156:159 arg1 protein 181:187 a type I integral membrane protein 154:187 a type I integral membrane protein that is expressed in the central nervous system 154:235 Myelin oligodendrocyte glycoprotein (MOG) is a type I integral membrane protein that is expressed in the central nervous system. 25541284 1 25 theme type 156:159 arg1 glycoprotein 132:143 Myelin oligodendrocyte glycoprotein 109:143 Myelin oligodendrocyte glycoprotein (MOG) 109:149 Myelin oligodendrocyte glycoprotein (MOG) is a type I integral membrane protein that is expressed in the central nervous system. 25541284 3 26 theme sclerosis 359:367 arg1 pathogenesis 334:345 pathogenesis 334:345 pathogenesis of multiple sclerosis 334:367 MOG has been linked with pathogenesis of multiple sclerosis; anti-MOG antibodies have been detected in the sera of multiple sclerosis patients. 25541284 3 27 located detected 400:407 arg2 antibodies 379:388 anti-MOG antibodies 370:388 anti-MOG antibodies 370:388 MOG has been linked with pathogenesis of multiple sclerosis; anti-MOG antibodies have been detected in the sera of multiple sclerosis patients. 25541284 3 27 located detected 400:407 arg1 sera 416:419 the sera 412:419 the sera of multiple sclerosis patients 412:450 MOG has been linked with pathogenesis of multiple sclerosis; anti-MOG antibodies have been detected in the sera of multiple sclerosis patients. 25541284 0 28 gly glycoprotein 89:100 arg1 glycoprotein 89:100 myelin oligodendrocyte glycoprotein 66:100 myelin oligodendrocyte glycoprotein (MOG) 66:106 The role of N-glycan in folding, trafficking and pathogenicity of myelin oligodendrocyte glycoprotein (MOG). 25541284 0 28 gly glycoprotein 89:100 arg1 MOG 103:105 MOG 103:105 MOG 103:105 The role of N-glycan in folding, trafficking and pathogenicity of myelin oligodendrocyte glycoprotein (MOG). 25541284 1 29 theme I 161:161 arg1 protein 181:187 a type I integral membrane protein 154:187 a type I integral membrane protein that is expressed in the central nervous system 154:235 Myelin oligodendrocyte glycoprotein (MOG) is a type I integral membrane protein that is expressed in the central nervous system. 25541284 1 29 theme I 161:161 arg1 glycoprotein 132:143 Myelin oligodendrocyte glycoprotein 109:143 Myelin oligodendrocyte glycoprotein (MOG) 109:149 Myelin oligodendrocyte glycoprotein (MOG) is a type I integral membrane protein that is expressed in the central nervous system. 25541284 0 30 theme N-glycan 12:19 arg1 role 4:7 The role 0:7 The role of N-glycan in folding, trafficking and pathogenicity of myelin oligodendrocyte glycoprotein (MOG). 0:107 The role of N-glycan in folding, trafficking and pathogenicity of myelin oligodendrocyte glycoprotein (MOG). 25541284 2 31 contain has 242:244 arg1 MOG 238:240 MOG 238:240 MOG 238:240 MOG has a single N-glycosylation site within its extracellular domain. 25541284 2 31 contain has 242:244 arg2 site 271:274 a single N-glycosylation site 246:274 a single N-glycosylation site within its extracellular domain 246:306 MOG has a single N-glycosylation site within its extracellular domain. 25541284 7 32 theme chaperone 869:877 arg1 calnexin 879:886 endoplasmic reticulum molecular chaperone calnexin 837:886 endoplasmic reticulum molecular chaperone calnexin 837:886 We concluded that the lack of sugar did not impact on MOG abundance in the absence of endoplasmic reticulum molecular chaperone calnexin. 25541284 7 33 theme sugar 781:785 arg1 lack 773:776 the lack 769:776 the lack of sugar 769:785 We concluded that the lack of sugar did not impact on MOG abundance in the absence of endoplasmic reticulum molecular chaperone calnexin. 25541284 1 34 theme integral 163:170 arg1 protein 181:187 a type I integral membrane protein 154:187 a type I integral membrane protein that is expressed in the central nervous system 154:235 Myelin oligodendrocyte glycoprotein (MOG) is a type I integral membrane protein that is expressed in the central nervous system. 25541284 1 34 theme integral 163:170 arg1 glycoprotein 132:143 Myelin oligodendrocyte glycoprotein 109:143 Myelin oligodendrocyte glycoprotein (MOG) 109:149 Myelin oligodendrocyte glycoprotein (MOG) is a type I integral membrane protein that is expressed in the central nervous system. 25541284 6 35 link N-linked 708:715 arg1 glycan 717:722 N-linked glycan 708:722 N-linked glycan 708:722 In this study, we created a mutant MOG lacking N-linked glycan and tested its properties. 25541284 2 36 theme N-glycosylation 255:269 arg1 site 271:274 a single N-glycosylation site 246:274 a single N-glycosylation site within its extracellular domain 246:306 MOG has a single N-glycosylation site within its extracellular domain. 25541284 1 37 theme membrane 172:179 arg1 protein 181:187 a type I integral membrane protein 154:187 a type I integral membrane protein that is expressed in the central nervous system 154:235 Myelin oligodendrocyte glycoprotein (MOG) is a type I integral membrane protein that is expressed in the central nervous system. 25541284 1 37 theme membrane 172:179 arg1 glycoprotein 132:143 Myelin oligodendrocyte glycoprotein 109:143 Myelin oligodendrocyte glycoprotein (MOG) 109:149 Myelin oligodendrocyte glycoprotein (MOG) is a type I integral membrane protein that is expressed in the central nervous system. 25541284 4 38 theme protein 520:526 arg1 N-glycosylation 453:467 N-glycosylation 453:467 N-glycosylation 453:467 N-glycosylation is an important post-translational modification of protein that might impact their folding, localization and function. 25541284 4 38 theme protein 520:526 arg1 modification 504:515 an important post-translational modification 472:515 an important post-translational modification of protein that might impact their folding, localization and function 472:585 N-glycosylation is an important post-translational modification of protein that might impact their folding, localization and function. 25541284 8 39 theme reticulum 1036:1044 arg1 stress 1046:1051 endoplasmic reticulum stress 1024:1051 endoplasmic reticulum stress 1024:1051 We also show that the absence of N-glycan did not interfere with MOG's subcellular localization and it did not result in activation of endoplasmic reticulum stress. 25541284 6 40 theme N-linked 708:715 arg1 glycan 717:722 N-linked glycan 708:722 N-linked glycan 708:722 In this study, we created a mutant MOG lacking N-linked glycan and tested its properties. 25541284 3 41 theme anti-MOG 370:377 arg1 antibodies 379:388 anti-MOG antibodies 370:388 anti-MOG antibodies 370:388 MOG has been linked with pathogenesis of multiple sclerosis; anti-MOG antibodies have been detected in the sera of multiple sclerosis patients. 25541284 1 42 gly glycoprotein 132:143 arg1 protein 181:187 a type I integral membrane protein 154:187 a type I integral membrane protein that is expressed in the central nervous system 154:235 Myelin oligodendrocyte glycoprotein (MOG) is a type I integral membrane protein that is expressed in the central nervous system. 25541284 1 42 gly glycoprotein 132:143 arg1 MOG 146:148 MOG 146:148 MOG 146:148 Myelin oligodendrocyte glycoprotein (MOG) is a type I integral membrane protein that is expressed in the central nervous system. 25541284 1 42 gly glycoprotein 132:143 arg1 glycoprotein 132:143 Myelin oligodendrocyte glycoprotein 109:143 Myelin oligodendrocyte glycoprotein (MOG) 109:149 Myelin oligodendrocyte glycoprotein (MOG) is a type I integral membrane protein that is expressed in the central nervous system. 25541284 7 43 theme endoplasmic 837:847 arg1 reticulum 849:857 endoplasmic reticulum 837:857 endoplasmic reticulum molecular chaperone calnexin 837:886 We concluded that the lack of sugar did not impact on MOG abundance in the absence of endoplasmic reticulum molecular chaperone calnexin. 25541284 1 44 theme Myelin 109:114 arg1 protein 181:187 a type I integral membrane protein 154:187 a type I integral membrane protein that is expressed in the central nervous system 154:235 Myelin oligodendrocyte glycoprotein (MOG) is a type I integral membrane protein that is expressed in the central nervous system. 25541284 1 44 theme Myelin 109:114 arg1 MOG 146:148 MOG 146:148 MOG 146:148 Myelin oligodendrocyte glycoprotein (MOG) is a type I integral membrane protein that is expressed in the central nervous system. 25541284 1 44 theme Myelin 109:114 arg1 glycoprotein 132:143 Myelin oligodendrocyte glycoprotein 109:143 Myelin oligodendrocyte glycoprotein (MOG) 109:149 Myelin oligodendrocyte glycoprotein (MOG) is a type I integral membrane protein that is expressed in the central nervous system. 25541284 7 45 theme reticulum 849:857 arg1 calnexin 879:886 endoplasmic reticulum molecular chaperone calnexin 837:886 endoplasmic reticulum molecular chaperone calnexin 837:886 We concluded that the lack of sugar did not impact on MOG abundance in the absence of endoplasmic reticulum molecular chaperone calnexin. 25541284 9 46 from Symposium 1118:1126 arg1 Calcium 1131:1137 Calcium 1131:1137 Calcium 1131:1137 This article is part of a Special Issue entitled: 13th European Symposium on Calcium. 25541284 8 47 theme stress 1046:1051 arg1 activation 1010:1019 activation 1010:1019 activation of endoplasmic reticulum stress 1010:1051 We also show that the absence of N-glycan did not interfere with MOG's subcellular localization and it did not result in activation of endoplasmic reticulum stress. 25541284 6 48 theme mutant 689:694 arg1 MOG 696:698 a mutant MOG 687:698 a mutant MOG lacking N-linked glycan 687:722 In this study, we created a mutant MOG lacking N-linked glycan and tested its properties. 25541284 1 49 theme oligodendrocyte 116:130 arg1 protein 181:187 a type I integral membrane protein 154:187 a type I integral membrane protein that is expressed in the central nervous system 154:235 Myelin oligodendrocyte glycoprotein (MOG) is a type I integral membrane protein that is expressed in the central nervous system. 25541284 1 49 theme oligodendrocyte 116:130 arg1 MOG 146:148 MOG 146:148 MOG 146:148 Myelin oligodendrocyte glycoprotein (MOG) is a type I integral membrane protein that is expressed in the central nervous system. 25541284 1 49 theme oligodendrocyte 116:130 arg1 glycoprotein 132:143 Myelin oligodendrocyte glycoprotein 109:143 Myelin oligodendrocyte glycoprotein (MOG) 109:149 Myelin oligodendrocyte glycoprotein (MOG) is a type I integral membrane protein that is expressed in the central nervous system. 25541284 9 50 theme European 1109:1116 arg1 Symposium 1118:1126 13th European Symposium 1104:1126 a Special Issue entitled: 13th European Symposium on Calcium 1078:1137 This article is part of a Special Issue entitled: 13th European Symposium on Calcium. 25541284 3 51 theme patients 443:450 arg1 sera 416:419 the sera 412:419 the sera of multiple sclerosis patients 412:450 MOG has been linked with pathogenesis of multiple sclerosis; anti-MOG antibodies have been detected in the sera of multiple sclerosis patients. 25541284 7 52 from impact 795:800 arg1 abundance 809:817 MOG abundance 805:817 MOG abundance in the absence of endoplasmic reticulum molecular chaperone calnexin 805:886 We concluded that the lack of sugar did not impact on MOG abundance in the absence of endoplasmic reticulum molecular chaperone calnexin. 25541284 3 53 theme multiple 424:431 arg1 patients 443:450 multiple sclerosis patients 424:450 multiple sclerosis patients 424:450 MOG has been linked with pathogenesis of multiple sclerosis; anti-MOG antibodies have been detected in the sera of multiple sclerosis patients. 25541284 4 54 theme important 475:483 arg1 N-glycosylation 453:467 N-glycosylation 453:467 N-glycosylation 453:467 N-glycosylation is an important post-translational modification of protein that might impact their folding, localization and function. 25541284 4 54 theme important 475:483 arg1 modification 504:515 an important post-translational modification 472:515 an important post-translational modification of protein that might impact their folding, localization and function 472:585 N-glycosylation is an important post-translational modification of protein that might impact their folding, localization and function. 25541284 9 55 theme Special 1080:1086 arg1 Issue 1088:1092 a Special Issue entitled 1078:1101 a Special Issue entitled: 13th European Symposium on Calcium 1078:1137 This article is part of a Special Issue entitled: 13th European Symposium on Calcium. 25541284 5 56 from role 601:604 arg1 biology 622:628 the biology 618:628 the biology of MOG 618:635 However, the role of sugar in the biology of MOG is not well understood. 26572842 0 0 theme selective 102:110 arg1 enrichment 112:121 highly selective enrichment 95:121 highly selective enrichment 95:121 Gold nanoparticles immobilized hydrophilic monoliths with variable functional modification for highly selective enrichment and on-line deglycosylation of glycopeptides. 26572842 3 1 theme alkaline 789:796 arg1 environment 798:808 weak alkaline environment 784:808 weak alkaline environment 784:808 Furthermore, the enrichment was specially achieved in weak alkaline environment, with 10 mM NH4HCO3 as the elution buffer, compatible with deglycosylation conditions. 26572842 2 2 theme hydrophilic 682:692 arg1 chromatography 706:719 hydrophilic interaction chromatography 682:719 hydrophilic interaction chromatography (HILIC) 682:727 By the cysteine functionalized monolithic column, glycopeptides could be efficiently and selectively enriched with good reproducibility based on hydrophilic interaction chromatography (HILIC). 26572842 2 2 theme hydrophilic 682:692 arg1 HILIC 722:726 HILIC 722:726 HILIC 722:726 By the cysteine functionalized monolithic column, glycopeptides could be efficiently and selectively enriched with good reproducibility based on hydrophilic interaction chromatography (HILIC). 26572842 0 3 with monoliths 43:51 arg1 modification 78:89 variable functional modification 58:89 variable functional modification for highly selective enrichment and on-line deglycosylation of glycopeptides 58:166 Gold nanoparticles immobilized hydrophilic monoliths with variable functional modification for highly selective enrichment and on-line deglycosylation of glycopeptides. 26572842 1 4 theme glycidyl 179:186 arg1 glycol 219:224 ethylene glycol 210:224 ethylene glycol 210:224 The poly (glycidyl methacrylate-co-poly (ethylene glycol) diacrylate) monoliths modified with gold nanoparticles, with advantages of enhanced reactive sites, good hydrophilicity and facile modification, were prepared as the matrix, followed by variable functionalization with cysteine and PNGase F for glycopeptide enrichment and on-line deglycosylation respectively. 26572842 1 4 theme glycidyl 179:186 arg1 methacrylate-co-poly 188:207 glycidyl methacrylate-co-poly 179:207 glycidyl methacrylate-co-poly (ethylene glycol) diacrylate 179:236 The poly (glycidyl methacrylate-co-poly (ethylene glycol) diacrylate) monoliths modified with gold nanoparticles, with advantages of enhanced reactive sites, good hydrophilicity and facile modification, were prepared as the matrix, followed by variable functionalization with cysteine and PNGase F for glycopeptide enrichment and on-line deglycosylation respectively. 26572842 4 5 theme adjustment 1153:1162 arg1 requirement 1115:1125 the requirement 1111:1125 the requirement of buffer exchange and pH adjustment 1111:1162 Therefore, the glycopeptides could be on-line deglycosylated with high efficiency and throughput by directly coupling the PNGase F functionalized monolithic column with the enrichment column during elution without the requirement of buffer exchange and pH adjustment. 26572842 5 6 theme N-linked 1220:1227 arg1 glycopeptides 1229:1241 196 N-linked glycopeptides 1216:1241 196 N-linked glycopeptides 1216:1241 By such a method, within only 70-min pretreatment, 196 N-linked glycopeptides, corresponding to 122 glycoproteins, could be identified from 5 μg of human plasma with 14 high-abundant proteins removed, and the N-linked glycopeptides occupied 81% of all identified peptides, achieving to the best of our knowledge, the highest selectivity of HILIC-based methods. 26572842 5 7 theme HILIC-based 1505:1515 arg1 methods 1517:1523 HILIC-based methods 1505:1523 HILIC-based methods 1505:1523 By such a method, within only 70-min pretreatment, 196 N-linked glycopeptides, corresponding to 122 glycoproteins, could be identified from 5 μg of human plasma with 14 high-abundant proteins removed, and the N-linked glycopeptides occupied 81% of all identified peptides, achieving to the best of our knowledge, the highest selectivity of HILIC-based methods. 26572842 1 8 theme methacrylate-co-poly 188:207 arg1 poly 173:176 poly 173:176 The poly (glycidyl methacrylate-co-poly (ethylene glycol) diacrylate) monoliths 169:247 The poly (glycidyl methacrylate-co-poly (ethylene glycol) diacrylate) monoliths modified with gold nanoparticles, with advantages of enhanced reactive sites, good hydrophilicity and facile modification, were prepared as the matrix, followed by variable functionalization with cysteine and PNGase F for glycopeptide enrichment and on-line deglycosylation respectively. 26572842 1 8 theme methacrylate-co-poly 188:207 arg1 diacrylate 227:236 glycidyl methacrylate-co-poly (ethylene glycol) diacrylate 179:236 glycidyl methacrylate-co-poly (ethylene glycol) diacrylate 179:236 The poly (glycidyl methacrylate-co-poly (ethylene glycol) diacrylate) monoliths modified with gold nanoparticles, with advantages of enhanced reactive sites, good hydrophilicity and facile modification, were prepared as the matrix, followed by variable functionalization with cysteine and PNGase F for glycopeptide enrichment and on-line deglycosylation respectively. 26572842 4 9 theme PNGase 1019:1024 arg1 F 1026:1026 PNGase F 1019:1026 PNGase F 1019:1026 Therefore, the glycopeptides could be on-line deglycosylated with high efficiency and throughput by directly coupling the PNGase F functionalized monolithic column with the enrichment column during elution without the requirement of buffer exchange and pH adjustment. 26572842 4 10 dep functionalized 1028:1041 arg1 F 1026:1026 PNGase F 1019:1026 PNGase F 1019:1026 Therefore, the glycopeptides could be on-line deglycosylated with high efficiency and throughput by directly coupling the PNGase F functionalized monolithic column with the enrichment column during elution without the requirement of buffer exchange and pH adjustment. 26572842 1 11 theme glycopeptide 471:482 arg1 enrichment 484:493 glycopeptide enrichment 471:493 glycopeptide enrichment 471:493 The poly (glycidyl methacrylate-co-poly (ethylene glycol) diacrylate) monoliths modified with gold nanoparticles, with advantages of enhanced reactive sites, good hydrophilicity and facile modification, were prepared as the matrix, followed by variable functionalization with cysteine and PNGase F for glycopeptide enrichment and on-line deglycosylation respectively. 26572842 6 12 theme proposed 1610:1617 arg1 strategy 1619:1626 our proposed strategy 1606:1626 our proposed strategy for the large scale glycoproteome analysis 1606:1669 All the results demonstrated the high efficiency, selectivity and throughput of our proposed strategy for the large scale glycoproteome analysis. 26572842 4 13 theme monolithic 1043:1052 arg1 column 1054:1059 the PNGase F functionalized monolithic column 1015:1059 the PNGase F functionalized monolithic column with the enrichment column 1015:1086 Therefore, the glycopeptides could be on-line deglycosylated with high efficiency and throughput by directly coupling the PNGase F functionalized monolithic column with the enrichment column during elution without the requirement of buffer exchange and pH adjustment. 26572842 6 14 theme strategy 1619:1626 arg1 efficiency 1564:1573 high efficiency 1559:1573 high efficiency 1559:1573 All the results demonstrated the high efficiency, selectivity and throughput of our proposed strategy for the large scale glycoproteome analysis. 26572842 6 14 theme strategy 1619:1626 arg1 throughput 1592:1601 throughput 1592:1601 throughput 1592:1601 All the results demonstrated the high efficiency, selectivity and throughput of our proposed strategy for the large scale glycoproteome analysis. 26572842 6 14 theme strategy 1619:1626 arg1 selectivity 1576:1586 selectivity 1576:1586 selectivity 1576:1586 All the results demonstrated the high efficiency, selectivity and throughput of our proposed strategy for the large scale glycoproteome analysis. 26572842 2 15 gly glycopeptides 587:599 arg2 glycopeptides 587:599 glycopeptides 587:599 glycopeptides 587:599 By the cysteine functionalized monolithic column, glycopeptides could be efficiently and selectively enriched with good reproducibility based on hydrophilic interaction chromatography (HILIC). 26572842 1 16 theme enhanced 302:309 arg1 sites 320:324 enhanced reactive sites 302:324 enhanced reactive sites 302:324 The poly (glycidyl methacrylate-co-poly (ethylene glycol) diacrylate) monoliths modified with gold nanoparticles, with advantages of enhanced reactive sites, good hydrophilicity and facile modification, were prepared as the matrix, followed by variable functionalization with cysteine and PNGase F for glycopeptide enrichment and on-line deglycosylation respectively. 26572842 3 17 theme 10 816:817 arg1 mM 819:820 mM 819:820 mM 819:820 Furthermore, the enrichment was specially achieved in weak alkaline environment, with 10 mM NH4HCO3 as the elution buffer, compatible with deglycosylation conditions. 26572842 3 18 with compatible 853:862 arg1 conditions 885:894 deglycosylation conditions 869:894 deglycosylation conditions 869:894 Furthermore, the enrichment was specially achieved in weak alkaline environment, with 10 mM NH4HCO3 as the elution buffer, compatible with deglycosylation conditions. 26572842 6 19 theme large 1636:1640 arg1 analysis 1662:1669 the large scale glycoproteome analysis 1632:1669 the large scale glycoproteome analysis 1632:1669 All the results demonstrated the high efficiency, selectivity and throughput of our proposed strategy for the large scale glycoproteome analysis. 26572842 5 20 theme identified 1417:1426 arg1 peptides 1428:1435 all identified peptides 1413:1435 all identified peptides 1413:1435 By such a method, within only 70-min pretreatment, 196 N-linked glycopeptides, corresponding to 122 glycoproteins, could be identified from 5 μg of human plasma with 14 high-abundant proteins removed, and the N-linked glycopeptides occupied 81% of all identified peptides, achieving to the best of our knowledge, the highest selectivity of HILIC-based methods. 26572842 4 21 theme high 963:966 arg1 efficiency 968:977 high efficiency 963:977 high efficiency 963:977 Therefore, the glycopeptides could be on-line deglycosylated with high efficiency and throughput by directly coupling the PNGase F functionalized monolithic column with the enrichment column during elution without the requirement of buffer exchange and pH adjustment. 26572842 0 22 theme on-line 127:133 arg1 deglycosylation 135:149 on-line deglycosylation 127:149 on-line deglycosylation 127:149 Gold nanoparticles immobilized hydrophilic monoliths with variable functional modification for highly selective enrichment and on-line deglycosylation of glycopeptides. 26572842 1 23 theme on-line 499:505 arg1 deglycosylation 507:521 on-line deglycosylation 499:521 on-line deglycosylation 499:521 The poly (glycidyl methacrylate-co-poly (ethylene glycol) diacrylate) monoliths modified with gold nanoparticles, with advantages of enhanced reactive sites, good hydrophilicity and facile modification, were prepared as the matrix, followed by variable functionalization with cysteine and PNGase F for glycopeptide enrichment and on-line deglycosylation respectively. 26572842 5 24 theme plasma 1319:1324 arg1 μg 1307:1308 5 μg 1305:1308 5 μg of human plasma with 14 high-abundant proteins removed 1305:1363 By such a method, within only 70-min pretreatment, 196 N-linked glycopeptides, corresponding to 122 glycoproteins, could be identified from 5 μg of human plasma with 14 high-abundant proteins removed, and the N-linked glycopeptides occupied 81% of all identified peptides, achieving to the best of our knowledge, the highest selectivity of HILIC-based methods. 26572842 5 25 theme peptides 1428:1435 arg1 % 1408:1408 81% 1406:1408 81% of all identified peptides 1406:1435 By such a method, within only 70-min pretreatment, 196 N-linked glycopeptides, corresponding to 122 glycoproteins, could be identified from 5 μg of human plasma with 14 high-abundant proteins removed, and the N-linked glycopeptides occupied 81% of all identified peptides, achieving to the best of our knowledge, the highest selectivity of HILIC-based methods. 26572842 5 25 theme peptides 1428:1435 arg1 peptides 1428:1435 all identified peptides 1413:1435 all identified peptides 1413:1435 By such a method, within only 70-min pretreatment, 196 N-linked glycopeptides, corresponding to 122 glycoproteins, could be identified from 5 μg of human plasma with 14 high-abundant proteins removed, and the N-linked glycopeptides occupied 81% of all identified peptides, achieving to the best of our knowledge, the highest selectivity of HILIC-based methods. 26572842 1 26 theme ethylene 210:217 arg1 glycol 219:224 ethylene glycol 210:224 ethylene glycol 210:224 The poly (glycidyl methacrylate-co-poly (ethylene glycol) diacrylate) monoliths modified with gold nanoparticles, with advantages of enhanced reactive sites, good hydrophilicity and facile modification, were prepared as the matrix, followed by variable functionalization with cysteine and PNGase F for glycopeptide enrichment and on-line deglycosylation respectively. 26572842 1 26 theme ethylene 210:217 arg1 methacrylate-co-poly 188:207 glycidyl methacrylate-co-poly 179:207 glycidyl methacrylate-co-poly (ethylene glycol) diacrylate 179:236 The poly (glycidyl methacrylate-co-poly (ethylene glycol) diacrylate) monoliths modified with gold nanoparticles, with advantages of enhanced reactive sites, good hydrophilicity and facile modification, were prepared as the matrix, followed by variable functionalization with cysteine and PNGase F for glycopeptide enrichment and on-line deglycosylation respectively. 26572842 4 27 theme exchange 1137:1144 arg1 requirement 1115:1125 the requirement 1111:1125 the requirement of buffer exchange and pH adjustment 1111:1162 Therefore, the glycopeptides could be on-line deglycosylated with high efficiency and throughput by directly coupling the PNGase F functionalized monolithic column with the enrichment column during elution without the requirement of buffer exchange and pH adjustment. 26572842 5 28 theme highest 1482:1488 arg1 selectivity 1490:1500 the highest selectivity 1478:1500 the highest selectivity of HILIC-based methods 1478:1523 By such a method, within only 70-min pretreatment, 196 N-linked glycopeptides, corresponding to 122 glycoproteins, could be identified from 5 μg of human plasma with 14 high-abundant proteins removed, and the N-linked glycopeptides occupied 81% of all identified peptides, achieving to the best of our knowledge, the highest selectivity of HILIC-based methods. 26572842 5 29 gly glycopeptides 1229:1241 arg2 glycopeptides 1229:1241 196 N-linked glycopeptides 1216:1241 196 N-linked glycopeptides 1216:1241 By such a method, within only 70-min pretreatment, 196 N-linked glycopeptides, corresponding to 122 glycoproteins, could be identified from 5 μg of human plasma with 14 high-abundant proteins removed, and the N-linked glycopeptides occupied 81% of all identified peptides, achieving to the best of our knowledge, the highest selectivity of HILIC-based methods. 26572842 4 30 theme buffer 1130:1135 arg1 exchange 1137:1144 buffer exchange 1130:1144 buffer exchange 1130:1144 Therefore, the glycopeptides could be on-line deglycosylated with high efficiency and throughput by directly coupling the PNGase F functionalized monolithic column with the enrichment column during elution without the requirement of buffer exchange and pH adjustment. 26572842 1 31 theme reactive 311:318 arg1 sites 320:324 enhanced reactive sites 302:324 enhanced reactive sites 302:324 The poly (glycidyl methacrylate-co-poly (ethylene glycol) diacrylate) monoliths modified with gold nanoparticles, with advantages of enhanced reactive sites, good hydrophilicity and facile modification, were prepared as the matrix, followed by variable functionalization with cysteine and PNGase F for glycopeptide enrichment and on-line deglycosylation respectively. 26572842 2 32 theme interaction 694:704 arg1 chromatography 706:719 hydrophilic interaction chromatography 682:719 hydrophilic interaction chromatography (HILIC) 682:727 By the cysteine functionalized monolithic column, glycopeptides could be efficiently and selectively enriched with good reproducibility based on hydrophilic interaction chromatography (HILIC). 26572842 2 32 theme interaction 694:704 arg1 HILIC 722:726 HILIC 722:726 HILIC 722:726 By the cysteine functionalized monolithic column, glycopeptides could be efficiently and selectively enriched with good reproducibility based on hydrophilic interaction chromatography (HILIC). 26572842 1 33 with functionalization 422:438 arg1 cysteine 445:452 cysteine 445:452 cysteine 445:452 The poly (glycidyl methacrylate-co-poly (ethylene glycol) diacrylate) monoliths modified with gold nanoparticles, with advantages of enhanced reactive sites, good hydrophilicity and facile modification, were prepared as the matrix, followed by variable functionalization with cysteine and PNGase F for glycopeptide enrichment and on-line deglycosylation respectively. 26572842 1 33 with functionalization 422:438 arg1 F 465:465 PNGase F 458:465 PNGase F 458:465 The poly (glycidyl methacrylate-co-poly (ethylene glycol) diacrylate) monoliths modified with gold nanoparticles, with advantages of enhanced reactive sites, good hydrophilicity and facile modification, were prepared as the matrix, followed by variable functionalization with cysteine and PNGase F for glycopeptide enrichment and on-line deglycosylation respectively. 26572842 0 34 theme hydrophilic 31:41 arg1 monoliths 43:51 immobilized hydrophilic monoliths 19:51 immobilized hydrophilic monoliths with variable functional modification for highly selective enrichment and on-line deglycosylation of glycopeptides 19:166 Gold nanoparticles immobilized hydrophilic monoliths with variable functional modification for highly selective enrichment and on-line deglycosylation of glycopeptides. 26572842 1 35 theme sites 320:324 arg1 advantages 288:297 advantages 288:297 advantages of enhanced reactive sites 288:324 The poly (glycidyl methacrylate-co-poly (ethylene glycol) diacrylate) monoliths modified with gold nanoparticles, with advantages of enhanced reactive sites, good hydrophilicity and facile modification, were prepared as the matrix, followed by variable functionalization with cysteine and PNGase F for glycopeptide enrichment and on-line deglycosylation respectively. 26572842 0 36 theme glycopeptides 154:166 arg1 enrichment 112:121 highly selective enrichment 95:121 highly selective enrichment 95:121 Gold nanoparticles immobilized hydrophilic monoliths with variable functional modification for highly selective enrichment and on-line deglycosylation of glycopeptides. 26572842 0 36 theme glycopeptides 154:166 arg1 deglycosylation 135:149 on-line deglycosylation 127:149 on-line deglycosylation 127:149 Gold nanoparticles immobilized hydrophilic monoliths with variable functional modification for highly selective enrichment and on-line deglycosylation of glycopeptides. 26572842 5 37 used occupied 1397:1404 arg2 glycopeptides 1383:1395 the N-linked glycopeptides 1370:1395 the N-linked glycopeptides 1370:1395 By such a method, within only 70-min pretreatment, 196 N-linked glycopeptides, corresponding to 122 glycoproteins, could be identified from 5 μg of human plasma with 14 high-abundant proteins removed, and the N-linked glycopeptides occupied 81% of all identified peptides, achieving to the best of our knowledge, the highest selectivity of HILIC-based methods. 26572842 0 38 theme immobilized 19:29 arg1 monoliths 43:51 immobilized hydrophilic monoliths 19:51 immobilized hydrophilic monoliths with variable functional modification for highly selective enrichment and on-line deglycosylation of glycopeptides 19:166 Gold nanoparticles immobilized hydrophilic monoliths with variable functional modification for highly selective enrichment and on-line deglycosylation of glycopeptides. 26572842 3 39 theme mM 819:820 arg1 NH4HCO3 822:828 10 mM NH4HCO3 816:828 10 mM NH4HCO3 as the elution buffer 816:850 Furthermore, the enrichment was specially achieved in weak alkaline environment, with 10 mM NH4HCO3 as the elution buffer, compatible with deglycosylation conditions. 26572842 0 40 gly deglycosylation 135:149 arg1 glycopeptides 154:166 glycopeptides 154:166 glycopeptides 154:166 Gold nanoparticles immobilized hydrophilic monoliths with variable functional modification for highly selective enrichment and on-line deglycosylation of glycopeptides. 26572842 1 41 theme good 327:330 arg1 monoliths 239:247 The poly (glycidyl methacrylate-co-poly (ethylene glycol) diacrylate) monoliths 169:247 The poly (glycidyl methacrylate-co-poly (ethylene glycol) diacrylate) monoliths 169:247 The poly (glycidyl methacrylate-co-poly (ethylene glycol) diacrylate) monoliths modified with gold nanoparticles, with advantages of enhanced reactive sites, good hydrophilicity and facile modification, were prepared as the matrix, followed by variable functionalization with cysteine and PNGase F for glycopeptide enrichment and on-line deglycosylation respectively. 26572842 1 41 theme good 327:330 arg1 hydrophilicity 332:345 good hydrophilicity 327:345 good hydrophilicity 327:345 The poly (glycidyl methacrylate-co-poly (ethylene glycol) diacrylate) monoliths modified with gold nanoparticles, with advantages of enhanced reactive sites, good hydrophilicity and facile modification, were prepared as the matrix, followed by variable functionalization with cysteine and PNGase F for glycopeptide enrichment and on-line deglycosylation respectively. 26572842 4 42 theme functionalized 1028:1041 arg1 column 1054:1059 the PNGase F functionalized monolithic column 1015:1059 the PNGase F functionalized monolithic column with the enrichment column 1015:1086 Therefore, the glycopeptides could be on-line deglycosylated with high efficiency and throughput by directly coupling the PNGase F functionalized monolithic column with the enrichment column during elution without the requirement of buffer exchange and pH adjustment. 26572842 1 43 theme variable 413:420 arg1 functionalization 422:438 variable functionalization 413:438 variable functionalization with cysteine and PNGase F for glycopeptide enrichment and on-line deglycosylation respectively 413:534 The poly (glycidyl methacrylate-co-poly (ethylene glycol) diacrylate) monoliths modified with gold nanoparticles, with advantages of enhanced reactive sites, good hydrophilicity and facile modification, were prepared as the matrix, followed by variable functionalization with cysteine and PNGase F for glycopeptide enrichment and on-line deglycosylation respectively. 26572842 5 44 link N-linked 1220:1227 arg1 glycopeptides 1229:1241 196 N-linked glycopeptides 1216:1241 196 N-linked glycopeptides 1216:1241 By such a method, within only 70-min pretreatment, 196 N-linked glycopeptides, corresponding to 122 glycoproteins, could be identified from 5 μg of human plasma with 14 high-abundant proteins removed, and the N-linked glycopeptides occupied 81% of all identified peptides, achieving to the best of our knowledge, the highest selectivity of HILIC-based methods. 26572842 3 45 theme elution 837:843 arg1 buffer 845:850 the elution buffer 833:850 the elution buffer 833:850 Furthermore, the enrichment was specially achieved in weak alkaline environment, with 10 mM NH4HCO3 as the elution buffer, compatible with deglycosylation conditions. 26572842 4 46 theme pH 1150:1151 arg1 adjustment 1153:1162 pH adjustment 1150:1162 pH adjustment 1150:1162 Therefore, the glycopeptides could be on-line deglycosylated with high efficiency and throughput by directly coupling the PNGase F functionalized monolithic column with the enrichment column during elution without the requirement of buffer exchange and pH adjustment. 26572842 5 47 with μg 1307:1308 arg1 proteins 1348:1355 14 high-abundant proteins 1331:1355 14 high-abundant proteins removed 1331:1363 By such a method, within only 70-min pretreatment, 196 N-linked glycopeptides, corresponding to 122 glycoproteins, could be identified from 5 μg of human plasma with 14 high-abundant proteins removed, and the N-linked glycopeptides occupied 81% of all identified peptides, achieving to the best of our knowledge, the highest selectivity of HILIC-based methods. 26572842 2 48 theme monolithic 568:577 arg1 column 579:584 the cysteine functionalized monolithic column 540:584 the cysteine functionalized monolithic column 540:584 By the cysteine functionalized monolithic column, glycopeptides could be efficiently and selectively enriched with good reproducibility based on hydrophilic interaction chromatography (HILIC). 26572842 0 49 theme functional 67:76 arg1 modification 78:89 variable functional modification 58:89 variable functional modification for highly selective enrichment and on-line deglycosylation of glycopeptides 58:166 Gold nanoparticles immobilized hydrophilic monoliths with variable functional modification for highly selective enrichment and on-line deglycosylation of glycopeptides. 26572842 2 50 theme good 652:655 arg1 reproducibility 657:671 good reproducibility 652:671 good reproducibility based on hydrophilic interaction chromatography (HILIC) 652:727 By the cysteine functionalized monolithic column, glycopeptides could be efficiently and selectively enriched with good reproducibility based on hydrophilic interaction chromatography (HILIC). 26572842 4 51 theme enrichment 1070:1079 arg1 column 1081:1086 the enrichment column 1066:1086 the enrichment column 1066:1086 Therefore, the glycopeptides could be on-line deglycosylated with high efficiency and throughput by directly coupling the PNGase F functionalized monolithic column with the enrichment column during elution without the requirement of buffer exchange and pH adjustment. 26572842 6 52 theme scale 1642:1646 arg1 analysis 1662:1669 the large scale glycoproteome analysis 1632:1669 the large scale glycoproteome analysis 1632:1669 All the results demonstrated the high efficiency, selectivity and throughput of our proposed strategy for the large scale glycoproteome analysis. 26572842 0 53 theme variable 58:65 arg1 modification 78:89 variable functional modification 58:89 variable functional modification for highly selective enrichment and on-line deglycosylation of glycopeptides 58:166 Gold nanoparticles immobilized hydrophilic monoliths with variable functional modification for highly selective enrichment and on-line deglycosylation of glycopeptides. 26572842 1 54 theme facile 351:356 arg1 monoliths 239:247 The poly (glycidyl methacrylate-co-poly (ethylene glycol) diacrylate) monoliths 169:247 The poly (glycidyl methacrylate-co-poly (ethylene glycol) diacrylate) monoliths 169:247 The poly (glycidyl methacrylate-co-poly (ethylene glycol) diacrylate) monoliths modified with gold nanoparticles, with advantages of enhanced reactive sites, good hydrophilicity and facile modification, were prepared as the matrix, followed by variable functionalization with cysteine and PNGase F for glycopeptide enrichment and on-line deglycosylation respectively. 26572842 1 54 theme facile 351:356 arg1 modification 358:369 facile modification 351:369 facile modification 351:369 The poly (glycidyl methacrylate-co-poly (ethylene glycol) diacrylate) monoliths modified with gold nanoparticles, with advantages of enhanced reactive sites, good hydrophilicity and facile modification, were prepared as the matrix, followed by variable functionalization with cysteine and PNGase F for glycopeptide enrichment and on-line deglycosylation respectively. 26572842 1 55 with monoliths 239:247 arg1 advantages 288:297 advantages 288:297 advantages of enhanced reactive sites 288:324 The poly (glycidyl methacrylate-co-poly (ethylene glycol) diacrylate) monoliths modified with gold nanoparticles, with advantages of enhanced reactive sites, good hydrophilicity and facile modification, were prepared as the matrix, followed by variable functionalization with cysteine and PNGase F for glycopeptide enrichment and on-line deglycosylation respectively. 26572842 5 56 link N-linked 1374:1381 arg1 glycopeptides 1383:1395 the N-linked glycopeptides 1370:1395 the N-linked glycopeptides 1370:1395 By such a method, within only 70-min pretreatment, 196 N-linked glycopeptides, corresponding to 122 glycoproteins, could be identified from 5 μg of human plasma with 14 high-abundant proteins removed, and the N-linked glycopeptides occupied 81% of all identified peptides, achieving to the best of our knowledge, the highest selectivity of HILIC-based methods. 26572842 0 57 gly glycopeptides 154:166 arg2 glycopeptides 154:166 glycopeptides 154:166 glycopeptides 154:166 Gold nanoparticles immobilized hydrophilic monoliths with variable functional modification for highly selective enrichment and on-line deglycosylation of glycopeptides. 26572842 5 58 dep occupied 1397:1404 arg1 achieving 1438:1446 achieving 1438:1446 achieving to the best of our knowledge 1438:1475 By such a method, within only 70-min pretreatment, 196 N-linked glycopeptides, corresponding to 122 glycoproteins, could be identified from 5 μg of human plasma with 14 high-abundant proteins removed, and the N-linked glycopeptides occupied 81% of all identified peptides, achieving to the best of our knowledge, the highest selectivity of HILIC-based methods. 26572842 5 59 theme 70-min 1195:1200 arg1 pretreatment 1202:1213 only 70-min pretreatment 1190:1213 only 70-min pretreatment 1190:1213 By such a method, within only 70-min pretreatment, 196 N-linked glycopeptides, corresponding to 122 glycoproteins, could be identified from 5 μg of human plasma with 14 high-abundant proteins removed, and the N-linked glycopeptides occupied 81% of all identified peptides, achieving to the best of our knowledge, the highest selectivity of HILIC-based methods. 26572842 5 60 theme methods 1517:1523 arg1 selectivity 1490:1500 the highest selectivity 1478:1500 the highest selectivity of HILIC-based methods 1478:1523 By such a method, within only 70-min pretreatment, 196 N-linked glycopeptides, corresponding to 122 glycoproteins, could be identified from 5 μg of human plasma with 14 high-abundant proteins removed, and the N-linked glycopeptides occupied 81% of all identified peptides, achieving to the best of our knowledge, the highest selectivity of HILIC-based methods. 26572842 5 61 gly glycoproteins 1265:1277 arg1 glycoproteins 1265:1277 122 glycoproteins 1261:1277 122 glycoproteins 1261:1277 By such a method, within only 70-min pretreatment, 196 N-linked glycopeptides, corresponding to 122 glycoproteins, could be identified from 5 μg of human plasma with 14 high-abundant proteins removed, and the N-linked glycopeptides occupied 81% of all identified peptides, achieving to the best of our knowledge, the highest selectivity of HILIC-based methods. 26572842 1 62 gly glycopeptide 471:482 arg2 glycopeptide 471:482 glycopeptide enrichment 471:493 glycopeptide enrichment 471:493 The poly (glycidyl methacrylate-co-poly (ethylene glycol) diacrylate) monoliths modified with gold nanoparticles, with advantages of enhanced reactive sites, good hydrophilicity and facile modification, were prepared as the matrix, followed by variable functionalization with cysteine and PNGase F for glycopeptide enrichment and on-line deglycosylation respectively. 26572842 1 63 theme PNGase 458:463 arg1 F 465:465 PNGase F 458:465 PNGase F 458:465 The poly (glycidyl methacrylate-co-poly (ethylene glycol) diacrylate) monoliths modified with gold nanoparticles, with advantages of enhanced reactive sites, good hydrophilicity and facile modification, were prepared as the matrix, followed by variable functionalization with cysteine and PNGase F for glycopeptide enrichment and on-line deglycosylation respectively. 26572842 6 64 dep efficiency 1564:1573 arg1 the 1555:1557 the 1555:1557 the 1555:1557 All the results demonstrated the high efficiency, selectivity and throughput of our proposed strategy for the large scale glycoproteome analysis. 26572842 5 65 theme N-linked 1374:1381 arg1 glycopeptides 1383:1395 the N-linked glycopeptides 1370:1395 the N-linked glycopeptides 1370:1395 By such a method, within only 70-min pretreatment, 196 N-linked glycopeptides, corresponding to 122 glycoproteins, could be identified from 5 μg of human plasma with 14 high-abundant proteins removed, and the N-linked glycopeptides occupied 81% of all identified peptides, achieving to the best of our knowledge, the highest selectivity of HILIC-based methods. 26572842 1 66 theme gold 263:266 arg1 nanoparticles 268:280 gold nanoparticles 263:280 gold nanoparticles 263:280 The poly (glycidyl methacrylate-co-poly (ethylene glycol) diacrylate) monoliths modified with gold nanoparticles, with advantages of enhanced reactive sites, good hydrophilicity and facile modification, were prepared as the matrix, followed by variable functionalization with cysteine and PNGase F for glycopeptide enrichment and on-line deglycosylation respectively. 26572842 2 67 theme functionalized 553:566 arg1 column 579:584 the cysteine functionalized monolithic column 540:584 the cysteine functionalized monolithic column 540:584 By the cysteine functionalized monolithic column, glycopeptides could be efficiently and selectively enriched with good reproducibility based on hydrophilic interaction chromatography (HILIC). 26572842 4 68 gly deglycosylated 943:956 arg1 on-line 935:941 on-line 935:941 on-line deglycosylated with high efficiency and throughput by directly coupling the PNGase F functionalized monolithic column with the enrichment column during elution without the requirement of buffer exchange and pH adjustment 935:1162 Therefore, the glycopeptides could be on-line deglycosylated with high efficiency and throughput by directly coupling the PNGase F functionalized monolithic column with the enrichment column during elution without the requirement of buffer exchange and pH adjustment. 26572842 4 68 gly deglycosylated 943:956 arg1 glycopeptides 912:924 the glycopeptides 908:924 the glycopeptides 908:924 Therefore, the glycopeptides could be on-line deglycosylated with high efficiency and throughput by directly coupling the PNGase F functionalized monolithic column with the enrichment column during elution without the requirement of buffer exchange and pH adjustment. 26572842 5 69 gly glycopeptides 1383:1395 arg2 glycopeptides 1383:1395 the N-linked glycopeptides 1370:1395 the N-linked glycopeptides 1370:1395 By such a method, within only 70-min pretreatment, 196 N-linked glycopeptides, corresponding to 122 glycoproteins, could be identified from 5 μg of human plasma with 14 high-abundant proteins removed, and the N-linked glycopeptides occupied 81% of all identified peptides, achieving to the best of our knowledge, the highest selectivity of HILIC-based methods. 26572842 6 70 theme glycoproteome 1648:1660 arg1 analysis 1662:1669 the large scale glycoproteome analysis 1632:1669 the large scale glycoproteome analysis 1632:1669 All the results demonstrated the high efficiency, selectivity and throughput of our proposed strategy for the large scale glycoproteome analysis. 26572842 1 71 theme poly 173:176 arg1 matrix 393:398 the matrix 389:398 the matrix 389:398 The poly (glycidyl methacrylate-co-poly (ethylene glycol) diacrylate) monoliths modified with gold nanoparticles, with advantages of enhanced reactive sites, good hydrophilicity and facile modification, were prepared as the matrix, followed by variable functionalization with cysteine and PNGase F for glycopeptide enrichment and on-line deglycosylation respectively. 26572842 1 71 theme poly 173:176 arg1 monoliths 239:247 The poly (glycidyl methacrylate-co-poly (ethylene glycol) diacrylate) monoliths 169:247 The poly (glycidyl methacrylate-co-poly (ethylene glycol) diacrylate) monoliths 169:247 The poly (glycidyl methacrylate-co-poly (ethylene glycol) diacrylate) monoliths modified with gold nanoparticles, with advantages of enhanced reactive sites, good hydrophilicity and facile modification, were prepared as the matrix, followed by variable functionalization with cysteine and PNGase F for glycopeptide enrichment and on-line deglycosylation respectively. 26572842 1 71 theme poly 173:176 arg1 hydrophilicity 332:345 good hydrophilicity 327:345 good hydrophilicity 327:345 The poly (glycidyl methacrylate-co-poly (ethylene glycol) diacrylate) monoliths modified with gold nanoparticles, with advantages of enhanced reactive sites, good hydrophilicity and facile modification, were prepared as the matrix, followed by variable functionalization with cysteine and PNGase F for glycopeptide enrichment and on-line deglycosylation respectively. 26572842 1 71 theme poly 173:176 arg1 modification 358:369 facile modification 351:369 facile modification 351:369 The poly (glycidyl methacrylate-co-poly (ethylene glycol) diacrylate) monoliths modified with gold nanoparticles, with advantages of enhanced reactive sites, good hydrophilicity and facile modification, were prepared as the matrix, followed by variable functionalization with cysteine and PNGase F for glycopeptide enrichment and on-line deglycosylation respectively. 26572842 6 72 theme high 1559:1562 arg1 efficiency 1564:1573 high efficiency 1559:1573 high efficiency 1559:1573 All the results demonstrated the high efficiency, selectivity and throughput of our proposed strategy for the large scale glycoproteome analysis. 26572842 2 73 theme cysteine 544:551 arg1 column 579:584 the cysteine functionalized monolithic column 540:584 the cysteine functionalized monolithic column 540:584 By the cysteine functionalized monolithic column, glycopeptides could be efficiently and selectively enriched with good reproducibility based on hydrophilic interaction chromatography (HILIC). 26572842 3 74 theme weak 784:787 arg1 environment 798:808 weak alkaline environment 784:808 weak alkaline environment 784:808 Furthermore, the enrichment was specially achieved in weak alkaline environment, with 10 mM NH4HCO3 as the elution buffer, compatible with deglycosylation conditions. 26572842 4 75 gly glycopeptides 912:924 arg2 glycopeptides 912:924 the glycopeptides 908:924 the glycopeptides 908:924 Therefore, the glycopeptides could be on-line deglycosylated with high efficiency and throughput by directly coupling the PNGase F functionalized monolithic column with the enrichment column during elution without the requirement of buffer exchange and pH adjustment. 26572842 4 75 gly glycopeptides 912:924 arg2 on-line 935:941 on-line 935:941 on-line deglycosylated with high efficiency and throughput by directly coupling the PNGase F functionalized monolithic column with the enrichment column during elution without the requirement of buffer exchange and pH adjustment 935:1162 Therefore, the glycopeptides could be on-line deglycosylated with high efficiency and throughput by directly coupling the PNGase F functionalized monolithic column with the enrichment column during elution without the requirement of buffer exchange and pH adjustment. 26572842 4 76 with column 1054:1059 arg1 column 1081:1086 the enrichment column 1066:1086 the enrichment column 1066:1086 Therefore, the glycopeptides could be on-line deglycosylated with high efficiency and throughput by directly coupling the PNGase F functionalized monolithic column with the enrichment column during elution without the requirement of buffer exchange and pH adjustment. 26572842 5 77 theme human 1313:1317 arg1 plasma 1319:1324 human plasma 1313:1324 human plasma 1313:1324 By such a method, within only 70-min pretreatment, 196 N-linked glycopeptides, corresponding to 122 glycoproteins, could be identified from 5 μg of human plasma with 14 high-abundant proteins removed, and the N-linked glycopeptides occupied 81% of all identified peptides, achieving to the best of our knowledge, the highest selectivity of HILIC-based methods. 26572842 5 78 theme high-abundant 1334:1346 arg1 proteins 1348:1355 14 high-abundant proteins 1331:1355 14 high-abundant proteins removed 1331:1363 By such a method, within only 70-min pretreatment, 196 N-linked glycopeptides, corresponding to 122 glycoproteins, could be identified from 5 μg of human plasma with 14 high-abundant proteins removed, and the N-linked glycopeptides occupied 81% of all identified peptides, achieving to the best of our knowledge, the highest selectivity of HILIC-based methods. 26572842 3 79 theme deglycosylation 869:883 arg1 conditions 885:894 deglycosylation conditions 869:894 deglycosylation conditions 869:894 Furthermore, the enrichment was specially achieved in weak alkaline environment, with 10 mM NH4HCO3 as the elution buffer, compatible with deglycosylation conditions. 26867740 4 0 theme O-GlcNAc 720:727 arg1 proteins/peptides 729:745 O-GlcNAc proteins/peptides 720:745 O-GlcNAc proteins/peptides from complex samples 720:766 In this chapter, we describe a recently developed approach for the identification and quantification of O-GlcNAc proteins/peptides from complex samples. 26867740 1 1 theme multiple 280:287 arg1 events 320:325 multiple physiological and pathological events 280:325 multiple physiological and pathological events 280:325 The dynamic co- and post-translational modification (PTM) of proteins, O-linked β-D-N-acetylglucosamine modification (O-GlcNAcylation) of serine/threonine residues is critical in many cellular processes, contributing to multiple physiological and pathological events. 26867740 2 2 theme complete 374:381 arg1 set 383:385 not only the complete set 361:385 not only the complete set of proteins that undergo O-GlcNAcylation but also the O-GlcNAc status at individual residues, as well as the dynamics of O-GlcNAcylation in response to various stimuli 361:553 The term "O-GlcNAcome" refers to not only the complete set of proteins that undergo O-GlcNAcylation but also the O-GlcNAc status at individual residues, as well as the dynamics of O-GlcNAcylation in response to various stimuli. 26867740 2 2 theme complete 374:381 arg1 proteins 390:397 proteins 390:397 proteins that undergo O-GlcNAcylation but also the O-GlcNAc status at individual residues, as well as the dynamics of O-GlcNAcylation in response to various stimuli 390:553 The term "O-GlcNAcome" refers to not only the complete set of proteins that undergo O-GlcNAcylation but also the O-GlcNAc status at individual residues, as well as the dynamics of O-GlcNAcylation in response to various stimuli. 26867740 4 3 from quantification 702:715 arg1 samples 760:766 complex samples 752:766 complex samples 752:766 In this chapter, we describe a recently developed approach for the identification and quantification of O-GlcNAc proteins/peptides from complex samples. 26867740 1 4 theme physiological 289:301 arg1 events 320:325 multiple physiological and pathological events 280:325 multiple physiological and pathological events 280:325 The dynamic co- and post-translational modification (PTM) of proteins, O-linked β-D-N-acetylglucosamine modification (O-GlcNAcylation) of serine/threonine residues is critical in many cellular processes, contributing to multiple physiological and pathological events. 26867740 2 5 from residues 471:478 arg1 O-GlcNAcylation 412:426 O-GlcNAcylation 412:426 O-GlcNAcylation 412:426 The term "O-GlcNAcome" refers to not only the complete set of proteins that undergo O-GlcNAcylation but also the O-GlcNAc status at individual residues, as well as the dynamics of O-GlcNAcylation in response to various stimuli. 26867740 2 5 from residues 471:478 arg1 dynamics 496:503 the dynamics 492:503 the dynamics of O-GlcNAcylation in response to various stimuli 492:553 The term "O-GlcNAcome" refers to not only the complete set of proteins that undergo O-GlcNAcylation but also the O-GlcNAc status at individual residues, as well as the dynamics of O-GlcNAcylation in response to various stimuli. 26867740 2 5 from residues 471:478 arg1 status 450:455 the O-GlcNAc status 437:455 the O-GlcNAc status at individual residues 437:478 The term "O-GlcNAcome" refers to not only the complete set of proteins that undergo O-GlcNAcylation but also the O-GlcNAc status at individual residues, as well as the dynamics of O-GlcNAcylation in response to various stimuli. 26867740 1 6 theme co- 72:74 arg1 PTM 113:115 PTM 113:115 PTM 113:115 The dynamic co- and post-translational modification (PTM) of proteins, O-linked β-D-N-acetylglucosamine modification (O-GlcNAcylation) of serine/threonine residues is critical in many cellular processes, contributing to multiple physiological and pathological events. 26867740 1 6 theme co- 72:74 arg1 modification 99:110 The dynamic co- and post-translational modification 60:110 The dynamic co- and post-translational modification (PTM) of proteins, O-linked β-D-N-acetylglucosamine modification (O-GlcNAcylation) of serine/threonine residues 60:222 The dynamic co- and post-translational modification (PTM) of proteins, O-linked β-D-N-acetylglucosamine modification (O-GlcNAcylation) of serine/threonine residues is critical in many cellular processes, contributing to multiple physiological and pathological events. 26867740 1 6 theme co- 72:74 arg1 critical 227:234 critical 227:234 critical 227:234 The dynamic co- and post-translational modification (PTM) of proteins, O-linked β-D-N-acetylglucosamine modification (O-GlcNAcylation) of serine/threonine residues is critical in many cellular processes, contributing to multiple physiological and pathological events. 26867740 2 7 theme various 539:545 arg1 stimuli 547:553 various stimuli 539:553 various stimuli 539:553 The term "O-GlcNAcome" refers to not only the complete set of proteins that undergo O-GlcNAcylation but also the O-GlcNAc status at individual residues, as well as the dynamics of O-GlcNAcylation in response to various stimuli. 26867740 4 8 from identification 683:696 arg1 samples 760:766 complex samples 752:766 complex samples 752:766 In this chapter, we describe a recently developed approach for the identification and quantification of O-GlcNAc proteins/peptides from complex samples. 26867740 1 9 theme pathological 307:318 arg1 events 320:325 multiple physiological and pathological events 280:325 multiple physiological and pathological events 280:325 The dynamic co- and post-translational modification (PTM) of proteins, O-linked β-D-N-acetylglucosamine modification (O-GlcNAcylation) of serine/threonine residues is critical in many cellular processes, contributing to multiple physiological and pathological events. 26867740 4 10 theme developed 656:664 arg1 approach 666:673 a recently developed approach 645:673 a recently developed approach for the identification and quantification of O-GlcNAc proteins/peptides from complex samples 645:766 In this chapter, we describe a recently developed approach for the identification and quantification of O-GlcNAc proteins/peptides from complex samples. 26867740 1 11 theme post-translational 80:97 arg1 PTM 113:115 PTM 113:115 PTM 113:115 The dynamic co- and post-translational modification (PTM) of proteins, O-linked β-D-N-acetylglucosamine modification (O-GlcNAcylation) of serine/threonine residues is critical in many cellular processes, contributing to multiple physiological and pathological events. 26867740 1 11 theme post-translational 80:97 arg1 modification 99:110 The dynamic co- and post-translational modification 60:110 The dynamic co- and post-translational modification (PTM) of proteins, O-linked β-D-N-acetylglucosamine modification (O-GlcNAcylation) of serine/threonine residues 60:222 The dynamic co- and post-translational modification (PTM) of proteins, O-linked β-D-N-acetylglucosamine modification (O-GlcNAcylation) of serine/threonine residues is critical in many cellular processes, contributing to multiple physiological and pathological events. 26867740 1 11 theme post-translational 80:97 arg1 critical 227:234 critical 227:234 critical 227:234 The dynamic co- and post-translational modification (PTM) of proteins, O-linked β-D-N-acetylglucosamine modification (O-GlcNAcylation) of serine/threonine residues is critical in many cellular processes, contributing to multiple physiological and pathological events. 26867740 3 12 theme O-GlcNAcomic 556:567 arg1 analyses 569:576 O-GlcNAcomic analyses 556:576 O-GlcNAcomic analyses 556:576 O-GlcNAcomic analyses have been a challenge for many years. 26867740 3 12 theme O-GlcNAcomic 556:567 arg1 challenge 590:598 a challenge 588:598 a challenge for many years 588:613 O-GlcNAcomic analyses have been a challenge for many years. 26867740 1 13 theme serine/threonine 198:213 arg1 residues 215:222 serine/threonine residues 198:222 serine/threonine residues 198:222 The dynamic co- and post-translational modification (PTM) of proteins, O-linked β-D-N-acetylglucosamine modification (O-GlcNAcylation) of serine/threonine residues is critical in many cellular processes, contributing to multiple physiological and pathological events. 26867740 0 14 theme Spectrometry-Based 5:22 arg1 Analysis 50:57 Mass Spectrometry-Based Quantitative O-GlcNAcomic Analysis 0:57 Mass Spectrometry-Based Quantitative O-GlcNAcomic Analysis 0:57 Mass Spectrometry-Based Quantitative O-GlcNAcomic Analysis. 26867740 1 15 theme residues 215:222 arg1 PTM 113:115 PTM 113:115 PTM 113:115 The dynamic co- and post-translational modification (PTM) of proteins, O-linked β-D-N-acetylglucosamine modification (O-GlcNAcylation) of serine/threonine residues is critical in many cellular processes, contributing to multiple physiological and pathological events. 26867740 1 15 theme residues 215:222 arg1 modification 99:110 The dynamic co- and post-translational modification 60:110 The dynamic co- and post-translational modification (PTM) of proteins, O-linked β-D-N-acetylglucosamine modification (O-GlcNAcylation) of serine/threonine residues 60:222 The dynamic co- and post-translational modification (PTM) of proteins, O-linked β-D-N-acetylglucosamine modification (O-GlcNAcylation) of serine/threonine residues is critical in many cellular processes, contributing to multiple physiological and pathological events. 26867740 1 15 theme residues 215:222 arg1 critical 227:234 critical 227:234 critical 227:234 The dynamic co- and post-translational modification (PTM) of proteins, O-linked β-D-N-acetylglucosamine modification (O-GlcNAcylation) of serine/threonine residues is critical in many cellular processes, contributing to multiple physiological and pathological events. 26867740 0 16 theme Mass 0:3 arg1 Analysis 50:57 Mass Spectrometry-Based Quantitative O-GlcNAcomic Analysis 0:57 Mass Spectrometry-Based Quantitative O-GlcNAcomic Analysis 0:57 Mass Spectrometry-Based Quantitative O-GlcNAcomic Analysis. 26867740 4 17 theme complex 752:758 arg1 samples 760:766 complex samples 752:766 complex samples 752:766 In this chapter, we describe a recently developed approach for the identification and quantification of O-GlcNAc proteins/peptides from complex samples. 26867740 0 18 theme O-GlcNAcomic 37:48 arg1 Analysis 50:57 Mass Spectrometry-Based Quantitative O-GlcNAcomic Analysis 0:57 Mass Spectrometry-Based Quantitative O-GlcNAcomic Analysis 0:57 Mass Spectrometry-Based Quantitative O-GlcNAcomic Analysis. 26867740 2 19 theme O-GlcNAcome 338:348 arg1 " 349:349 The term "O-GlcNAcome" 328:349 The term "O-GlcNAcome" 328:349 The term "O-GlcNAcome" refers to not only the complete set of proteins that undergo O-GlcNAcylation but also the O-GlcNAc status at individual residues, as well as the dynamics of O-GlcNAcylation in response to various stimuli. 26867740 0 20 theme Quantitative 24:35 arg1 Analysis 50:57 Mass Spectrometry-Based Quantitative O-GlcNAcomic Analysis 0:57 Mass Spectrometry-Based Quantitative O-GlcNAcomic Analysis 0:57 Mass Spectrometry-Based Quantitative O-GlcNAcomic Analysis. 26867740 2 21 theme O-GlcNAc 441:448 arg1 status 450:455 the O-GlcNAc status 437:455 the O-GlcNAc status at individual residues 437:478 The term "O-GlcNAcome" refers to not only the complete set of proteins that undergo O-GlcNAcylation but also the O-GlcNAc status at individual residues, as well as the dynamics of O-GlcNAcylation in response to various stimuli. 26867740 2 22 from dynamics 496:503 arg1 response 527:534 response 527:534 response to various stimuli 527:553 The term "O-GlcNAcome" refers to not only the complete set of proteins that undergo O-GlcNAcylation but also the O-GlcNAc status at individual residues, as well as the dynamics of O-GlcNAcylation in response to various stimuli. 26867740 1 23 theme many 239:242 arg1 processes 253:261 many cellular processes 239:261 many cellular processes 239:261 The dynamic co- and post-translational modification (PTM) of proteins, O-linked β-D-N-acetylglucosamine modification (O-GlcNAcylation) of serine/threonine residues is critical in many cellular processes, contributing to multiple physiological and pathological events. 26867740 2 24 theme individual 460:469 arg1 residues 471:478 individual residues 460:478 individual residues 460:478 The term "O-GlcNAcome" refers to not only the complete set of proteins that undergo O-GlcNAcylation but also the O-GlcNAc status at individual residues, as well as the dynamics of O-GlcNAcylation in response to various stimuli. 26867740 1 25 theme cellular 244:251 arg1 processes 253:261 many cellular processes 239:261 many cellular processes 239:261 The dynamic co- and post-translational modification (PTM) of proteins, O-linked β-D-N-acetylglucosamine modification (O-GlcNAcylation) of serine/threonine residues is critical in many cellular processes, contributing to multiple physiological and pathological events. 26867740 1 26 link O-linked 131:138 arg1 proteins 121:128 proteins 121:128 proteins 121:128 The dynamic co- and post-translational modification (PTM) of proteins, O-linked β-D-N-acetylglucosamine modification (O-GlcNAcylation) of serine/threonine residues is critical in many cellular processes, contributing to multiple physiological and pathological events. 26867740 1 26 link O-linked 131:138 arg1 O-GlcNAcylation 178:192 O-GlcNAcylation 178:192 O-GlcNAcylation 178:192 The dynamic co- and post-translational modification (PTM) of proteins, O-linked β-D-N-acetylglucosamine modification (O-GlcNAcylation) of serine/threonine residues is critical in many cellular processes, contributing to multiple physiological and pathological events. 26867740 1 26 link O-linked 131:138 arg1 modification 164:175 O-linked β-D-N-acetylglucosamine modification 131:175 O-linked β-D-N-acetylglucosamine modification (O-GlcNAcylation) 131:193 The dynamic co- and post-translational modification (PTM) of proteins, O-linked β-D-N-acetylglucosamine modification (O-GlcNAcylation) of serine/threonine residues is critical in many cellular processes, contributing to multiple physiological and pathological events. 26867740 3 27 theme many 604:607 arg1 years 609:613 many years 604:613 many years 604:613 O-GlcNAcomic analyses have been a challenge for many years. 26867740 1 28 theme proteins 121:128 arg1 PTM 113:115 PTM 113:115 PTM 113:115 The dynamic co- and post-translational modification (PTM) of proteins, O-linked β-D-N-acetylglucosamine modification (O-GlcNAcylation) of serine/threonine residues is critical in many cellular processes, contributing to multiple physiological and pathological events. 26867740 1 28 theme proteins 121:128 arg1 modification 99:110 The dynamic co- and post-translational modification 60:110 The dynamic co- and post-translational modification (PTM) of proteins, O-linked β-D-N-acetylglucosamine modification (O-GlcNAcylation) of serine/threonine residues 60:222 The dynamic co- and post-translational modification (PTM) of proteins, O-linked β-D-N-acetylglucosamine modification (O-GlcNAcylation) of serine/threonine residues is critical in many cellular processes, contributing to multiple physiological and pathological events. 26867740 1 28 theme proteins 121:128 arg1 critical 227:234 critical 227:234 critical 227:234 The dynamic co- and post-translational modification (PTM) of proteins, O-linked β-D-N-acetylglucosamine modification (O-GlcNAcylation) of serine/threonine residues is critical in many cellular processes, contributing to multiple physiological and pathological events. 26867740 1 29 from critical 227:234 arg1 processes 253:261 many cellular processes 239:261 many cellular processes 239:261 The dynamic co- and post-translational modification (PTM) of proteins, O-linked β-D-N-acetylglucosamine modification (O-GlcNAcylation) of serine/threonine residues is critical in many cellular processes, contributing to multiple physiological and pathological events. 26867740 4 30 theme proteins/peptides 729:745 arg1 quantification 702:715 quantification 702:715 quantification 702:715 In this chapter, we describe a recently developed approach for the identification and quantification of O-GlcNAc proteins/peptides from complex samples. 26867740 4 30 theme proteins/peptides 729:745 arg1 identification 683:696 identification 683:696 identification 683:696 In this chapter, we describe a recently developed approach for the identification and quantification of O-GlcNAc proteins/peptides from complex samples. 26867740 4 31 from samples 760:766 arg1 quantification 702:715 quantification 702:715 quantification 702:715 In this chapter, we describe a recently developed approach for the identification and quantification of O-GlcNAc proteins/peptides from complex samples. 26867740 4 31 from samples 760:766 arg1 proteins/peptides 729:745 O-GlcNAc proteins/peptides 720:745 O-GlcNAc proteins/peptides from complex samples 720:766 In this chapter, we describe a recently developed approach for the identification and quantification of O-GlcNAc proteins/peptides from complex samples. 26867740 4 31 from samples 760:766 arg1 identification 683:696 identification 683:696 identification 683:696 In this chapter, we describe a recently developed approach for the identification and quantification of O-GlcNAc proteins/peptides from complex samples. 26867740 1 32 from processes 253:261 arg1 modification 99:110 The dynamic co- and post-translational modification 60:110 The dynamic co- and post-translational modification (PTM) of proteins, O-linked β-D-N-acetylglucosamine modification (O-GlcNAcylation) of serine/threonine residues 60:222 The dynamic co- and post-translational modification (PTM) of proteins, O-linked β-D-N-acetylglucosamine modification (O-GlcNAcylation) of serine/threonine residues is critical in many cellular processes, contributing to multiple physiological and pathological events. 26867740 1 32 from processes 253:261 arg1 critical 227:234 critical 227:234 critical 227:234 The dynamic co- and post-translational modification (PTM) of proteins, O-linked β-D-N-acetylglucosamine modification (O-GlcNAcylation) of serine/threonine residues is critical in many cellular processes, contributing to multiple physiological and pathological events. 26867740 4 33 dep identification 683:696 arg1 the 679:681 the 679:681 the 679:681 In this chapter, we describe a recently developed approach for the identification and quantification of O-GlcNAc proteins/peptides from complex samples. 26867740 2 34 from O-GlcNAcylation 412:426 arg1 response 527:534 response 527:534 response to various stimuli 527:553 The term "O-GlcNAcome" refers to not only the complete set of proteins that undergo O-GlcNAcylation but also the O-GlcNAc status at individual residues, as well as the dynamics of O-GlcNAcylation in response to various stimuli. 26867740 1 35 theme O-linked 131:138 arg1 proteins 121:128 proteins 121:128 proteins 121:128 The dynamic co- and post-translational modification (PTM) of proteins, O-linked β-D-N-acetylglucosamine modification (O-GlcNAcylation) of serine/threonine residues is critical in many cellular processes, contributing to multiple physiological and pathological events. 26867740 1 35 theme O-linked 131:138 arg1 O-GlcNAcylation 178:192 O-GlcNAcylation 178:192 O-GlcNAcylation 178:192 The dynamic co- and post-translational modification (PTM) of proteins, O-linked β-D-N-acetylglucosamine modification (O-GlcNAcylation) of serine/threonine residues is critical in many cellular processes, contributing to multiple physiological and pathological events. 26867740 1 35 theme O-linked 131:138 arg1 modification 164:175 O-linked β-D-N-acetylglucosamine modification 131:175 O-linked β-D-N-acetylglucosamine modification (O-GlcNAcylation) 131:193 The dynamic co- and post-translational modification (PTM) of proteins, O-linked β-D-N-acetylglucosamine modification (O-GlcNAcylation) of serine/threonine residues is critical in many cellular processes, contributing to multiple physiological and pathological events. 26867740 2 36 theme term 332:335 arg1 " 349:349 The term "O-GlcNAcome" 328:349 The term "O-GlcNAcome" 328:349 The term "O-GlcNAcome" refers to not only the complete set of proteins that undergo O-GlcNAcylation but also the O-GlcNAc status at individual residues, as well as the dynamics of O-GlcNAcylation in response to various stimuli. 26867740 1 37 theme β-D-N-acetylglucosamine 140:162 arg1 proteins 121:128 proteins 121:128 proteins 121:128 The dynamic co- and post-translational modification (PTM) of proteins, O-linked β-D-N-acetylglucosamine modification (O-GlcNAcylation) of serine/threonine residues is critical in many cellular processes, contributing to multiple physiological and pathological events. 26867740 1 37 theme β-D-N-acetylglucosamine 140:162 arg1 O-GlcNAcylation 178:192 O-GlcNAcylation 178:192 O-GlcNAcylation 178:192 The dynamic co- and post-translational modification (PTM) of proteins, O-linked β-D-N-acetylglucosamine modification (O-GlcNAcylation) of serine/threonine residues is critical in many cellular processes, contributing to multiple physiological and pathological events. 26867740 1 37 theme β-D-N-acetylglucosamine 140:162 arg1 modification 164:175 O-linked β-D-N-acetylglucosamine modification 131:175 O-linked β-D-N-acetylglucosamine modification (O-GlcNAcylation) 131:193 The dynamic co- and post-translational modification (PTM) of proteins, O-linked β-D-N-acetylglucosamine modification (O-GlcNAcylation) of serine/threonine residues is critical in many cellular processes, contributing to multiple physiological and pathological events. 26867740 2 38 theme proteins 390:397 arg1 set 383:385 not only the complete set 361:385 not only the complete set of proteins that undergo O-GlcNAcylation but also the O-GlcNAc status at individual residues, as well as the dynamics of O-GlcNAcylation in response to various stimuli 361:553 The term "O-GlcNAcome" refers to not only the complete set of proteins that undergo O-GlcNAcylation but also the O-GlcNAc status at individual residues, as well as the dynamics of O-GlcNAcylation in response to various stimuli. 26867740 2 38 theme proteins 390:397 arg1 proteins 390:397 proteins 390:397 proteins that undergo O-GlcNAcylation but also the O-GlcNAc status at individual residues, as well as the dynamics of O-GlcNAcylation in response to various stimuli 390:553 The term "O-GlcNAcome" refers to not only the complete set of proteins that undergo O-GlcNAcylation but also the O-GlcNAc status at individual residues, as well as the dynamics of O-GlcNAcylation in response to various stimuli. 26867740 2 39 theme O-GlcNAcylation 508:522 arg1 O-GlcNAcylation 412:426 O-GlcNAcylation 412:426 O-GlcNAcylation 412:426 The term "O-GlcNAcome" refers to not only the complete set of proteins that undergo O-GlcNAcylation but also the O-GlcNAc status at individual residues, as well as the dynamics of O-GlcNAcylation in response to various stimuli. 26867740 2 39 theme O-GlcNAcylation 508:522 arg1 dynamics 496:503 the dynamics 492:503 the dynamics of O-GlcNAcylation in response to various stimuli 492:553 The term "O-GlcNAcome" refers to not only the complete set of proteins that undergo O-GlcNAcylation but also the O-GlcNAc status at individual residues, as well as the dynamics of O-GlcNAcylation in response to various stimuli. 26867740 2 39 theme O-GlcNAcylation 508:522 arg1 status 450:455 the O-GlcNAc status 437:455 the O-GlcNAc status at individual residues 437:478 The term "O-GlcNAcome" refers to not only the complete set of proteins that undergo O-GlcNAcylation but also the O-GlcNAc status at individual residues, as well as the dynamics of O-GlcNAcylation in response to various stimuli. 26867740 1 40 theme dynamic 64:70 arg1 PTM 113:115 PTM 113:115 PTM 113:115 The dynamic co- and post-translational modification (PTM) of proteins, O-linked β-D-N-acetylglucosamine modification (O-GlcNAcylation) of serine/threonine residues is critical in many cellular processes, contributing to multiple physiological and pathological events. 26867740 1 40 theme dynamic 64:70 arg1 modification 99:110 The dynamic co- and post-translational modification 60:110 The dynamic co- and post-translational modification (PTM) of proteins, O-linked β-D-N-acetylglucosamine modification (O-GlcNAcylation) of serine/threonine residues 60:222 The dynamic co- and post-translational modification (PTM) of proteins, O-linked β-D-N-acetylglucosamine modification (O-GlcNAcylation) of serine/threonine residues is critical in many cellular processes, contributing to multiple physiological and pathological events. 26867740 1 40 theme dynamic 64:70 arg1 critical 227:234 critical 227:234 critical 227:234 The dynamic co- and post-translational modification (PTM) of proteins, O-linked β-D-N-acetylglucosamine modification (O-GlcNAcylation) of serine/threonine residues is critical in many cellular processes, contributing to multiple physiological and pathological events. 26867740 2 41 from status 450:455 arg1 response 527:534 response 527:534 response to various stimuli 527:553 The term "O-GlcNAcome" refers to not only the complete set of proteins that undergo O-GlcNAcylation but also the O-GlcNAc status at individual residues, as well as the dynamics of O-GlcNAcylation in response to various stimuli. 28062574 5 0 theme reduced 848:854 arg1 expression 856:865 reduced expression 848:865 reduced expression of GALNT4 848:875 GALNT4 expression is markedly repressed in primary HCC tissues, and reduced expression of GALNT4 is significantly associated with adverse survival of patients with HCC. 28062574 10 1 theme miR-9/GALNT4 1684:1695 arg1 axis 1697:1700 the miR-9/GALNT4 axis 1680:1700 the miR-9/GALNT4 axis 1680:1700 In conclusion, this study establishes the miR-9/GALNT4 axis as a potential adverse prognostic factor and therapeutic target for HCC patients. 28062574 10 1 theme miR-9/GALNT4 1684:1695 arg1 target 1759:1764 a potential adverse prognostic factor and therapeutic target 1705:1764 a potential adverse prognostic factor and therapeutic target for HCC patients 1705:1781 In conclusion, this study establishes the miR-9/GALNT4 axis as a potential adverse prognostic factor and therapeutic target for HCC patients. 28062574 9 2 theme miR-9/GALNT4 1511:1522 arg1 signature 1535:1543 the miR-9/GALNT4 expression signature 1507:1543 the miR-9/GALNT4 expression signature 1507:1543 Kaplan-Meier survival analysis indicates that the miR-9/GALNT4 expression signature yields promising prognostic significance to refine the risk stratification of patients with HCC. 28062574 2 3 theme partial 420:426 arg1 substrates 448:457 partial GalNAc-glycosylated substrates 420:457 partial GalNAc-glycosylated substrates 420:457 GALNT4 is one of the few isoforms preferring to catalyze partial GalNAc-glycosylated substrates and modify the sites not utilized by other known GALNTs. 28062574 4 4 theme in 664:665 arg1 hybridization 672:684 in situ hybridization 664:684 in situ hybridization analysis 664:693 Immunohistochemistry and in situ hybridization analysis were performed to assess GALNT4 and miR-9 level in clinical specimens, respectively. 28062574 8 5 theme GALNT4 1396:1401 arg1 expression 1403:1412 restoring GALNT4 expression 1386:1412 restoring GALNT4 expression 1386:1412 Furthermore, restoring GALNT4 expression attenuates miR-9-mediated oncogenic functions. 28062574 6 6 link O-linked 1165:1172 arg1 glycosylation 1174:1186 O-linked glycosylation 1165:1186 O-linked glycosylation on EGFR 1165:1194 Functional investigations demonstrate that repressed GALNT4 could promote migration, invasion, anoikis resistance, and stemness of HCC cells in vitro as well as tumor growth in vivo The wild-type GALNT4 could modify O-linked glycosylation on EGFR and thus modulate the activity of EGFR. 28062574 9 7 theme risk 1600:1603 arg1 stratification 1605:1618 the risk stratification 1596:1618 the risk stratification of patients with HCC 1596:1639 Kaplan-Meier survival analysis indicates that the miR-9/GALNT4 expression signature yields promising prognostic significance to refine the risk stratification of patients with HCC. 28062574 1 8 theme initial 207:213 arg1 step 215:218 the initial step 203:218 the initial step of mucin-type O-glycosylation 203:248 Deregulated expression of N-acetylgalactosaminyltransferases (GALNTs), which is responsible for the initial step of mucin-type O-glycosylation, could produce abnormal truncated O-glycans and thereby exert pivotal functions during malignant transformation. 28062574 6 9 theme Functional 949:958 arg1 investigations 960:973 Functional investigations 949:973 Functional investigations 949:973 Functional investigations demonstrate that repressed GALNT4 could promote migration, invasion, anoikis resistance, and stemness of HCC cells in vitro as well as tumor growth in vivo The wild-type GALNT4 could modify O-linked glycosylation on EGFR and thus modulate the activity of EGFR. 28062574 1 10 theme pivotal 312:318 arg1 functions 320:328 pivotal functions 312:328 pivotal functions 312:328 Deregulated expression of N-acetylgalactosaminyltransferases (GALNTs), which is responsible for the initial step of mucin-type O-glycosylation, could produce abnormal truncated O-glycans and thereby exert pivotal functions during malignant transformation. 28062574 10 11 theme prognostic 1725:1734 arg1 factor 1736:1741 adverse prognostic factor 1717:1741 adverse prognostic factor 1717:1741 In conclusion, this study establishes the miR-9/GALNT4 axis as a potential adverse prognostic factor and therapeutic target for HCC patients. 28062574 6 12 gly glycosylation 1174:1186 arg1 EGFR 1191:1194 EGFR 1191:1194 EGFR 1191:1194 Functional investigations demonstrate that repressed GALNT4 could promote migration, invasion, anoikis resistance, and stemness of HCC cells in vitro as well as tumor growth in vivo The wild-type GALNT4 could modify O-linked glycosylation on EGFR and thus modulate the activity of EGFR. 28062574 3 13 theme carcinoma 622:630 arg1 transformation 589:602 malignant transformation 579:602 malignant transformation of hepatocellular carcinoma (HCC) 579:636 This study aims to evaluate the impact of GALNT4 expression on malignant transformation of hepatocellular carcinoma (HCC). 28062574 6 14 from glycosylation 1174:1186 arg1 EGFR 1191:1194 EGFR 1191:1194 EGFR 1191:1194 Functional investigations demonstrate that repressed GALNT4 could promote migration, invasion, anoikis resistance, and stemness of HCC cells in vitro as well as tumor growth in vivo The wild-type GALNT4 could modify O-linked glycosylation on EGFR and thus modulate the activity of EGFR. 28062574 4 15 theme hybridization 672:684 arg1 analysis 686:693 in situ hybridization analysis 664:693 in situ hybridization analysis 664:693 Immunohistochemistry and in situ hybridization analysis were performed to assess GALNT4 and miR-9 level in clinical specimens, respectively. 28062574 5 16 theme primary 823:829 arg1 tissues 835:841 primary HCC tissues 823:841 primary HCC tissues 823:841 GALNT4 expression is markedly repressed in primary HCC tissues, and reduced expression of GALNT4 is significantly associated with adverse survival of patients with HCC. 28062574 8 17 theme oncogenic 1440:1448 arg1 functions 1450:1458 miR-9-mediated oncogenic functions 1425:1458 miR-9-mediated oncogenic functions 1425:1458 Furthermore, restoring GALNT4 expression attenuates miR-9-mediated oncogenic functions. 28062574 10 18 theme HCC 1770:1772 arg1 patients 1774:1781 HCC patients 1770:1781 HCC patients 1770:1781 In conclusion, this study establishes the miR-9/GALNT4 axis as a potential adverse prognostic factor and therapeutic target for HCC patients. 28062574 3 19 theme expression 565:574 arg1 impact 548:553 the impact 544:553 the impact of GALNT4 expression on malignant transformation of hepatocellular carcinoma (HCC) 544:636 This study aims to evaluate the impact of GALNT4 expression on malignant transformation of hepatocellular carcinoma (HCC). 28062574 6 20 theme cells 1084:1088 arg1 resistance 1052:1061 anoikis resistance 1044:1061 anoikis resistance 1044:1061 Functional investigations demonstrate that repressed GALNT4 could promote migration, invasion, anoikis resistance, and stemness of HCC cells in vitro as well as tumor growth in vivo The wild-type GALNT4 could modify O-linked glycosylation on EGFR and thus modulate the activity of EGFR. 28062574 6 20 theme cells 1084:1088 arg1 migration 1023:1031 migration 1023:1031 migration 1023:1031 Functional investigations demonstrate that repressed GALNT4 could promote migration, invasion, anoikis resistance, and stemness of HCC cells in vitro as well as tumor growth in vivo The wild-type GALNT4 could modify O-linked glycosylation on EGFR and thus modulate the activity of EGFR. 28062574 6 20 theme cells 1084:1088 arg1 invasion 1034:1041 invasion 1034:1041 invasion 1034:1041 Functional investigations demonstrate that repressed GALNT4 could promote migration, invasion, anoikis resistance, and stemness of HCC cells in vitro as well as tumor growth in vivo The wild-type GALNT4 could modify O-linked glycosylation on EGFR and thus modulate the activity of EGFR. 28062574 6 20 theme cells 1084:1088 arg1 stemness 1068:1075 stemness 1068:1075 stemness 1068:1075 Functional investigations demonstrate that repressed GALNT4 could promote migration, invasion, anoikis resistance, and stemness of HCC cells in vitro as well as tumor growth in vivo The wild-type GALNT4 could modify O-linked glycosylation on EGFR and thus modulate the activity of EGFR. 28062574 6 20 theme cells 1084:1088 arg1 growth 1116:1121 tumor growth 1110:1121 migration, invasion, anoikis resistance, and stemness of HCC cells in vitro as well as tumor growth 1023:1121 Functional investigations demonstrate that repressed GALNT4 could promote migration, invasion, anoikis resistance, and stemness of HCC cells in vitro as well as tumor growth in vivo The wild-type GALNT4 could modify O-linked glycosylation on EGFR and thus modulate the activity of EGFR. 28062574 5 21 theme HCC 831:833 arg1 tissues 835:841 primary HCC tissues 823:841 primary HCC tissues 823:841 GALNT4 expression is markedly repressed in primary HCC tissues, and reduced expression of GALNT4 is significantly associated with adverse survival of patients with HCC. 28062574 7 22 theme activity 1249:1256 arg1 assay 1258:1262 A luciferase activity assay 1236:1262 A luciferase activity assay 1236:1262 A luciferase activity assay further identified microRNA-9 (miR-9) as the crucial specific arbitrator for GALNT4 expression in HCC cells. 28062574 1 23 theme Deregulated 107:117 arg1 expression 119:128 Deregulated expression 107:128 Deregulated expression 107:128 Deregulated expression of N-acetylgalactosaminyltransferases (GALNTs), which is responsible for the initial step of mucin-type O-glycosylation, could produce abnormal truncated O-glycans and thereby exert pivotal functions during malignant transformation. 28062574 6 24 theme O-linked 1165:1172 arg1 glycosylation 1174:1186 O-linked glycosylation 1165:1186 O-linked glycosylation on EGFR 1165:1194 Functional investigations demonstrate that repressed GALNT4 could promote migration, invasion, anoikis resistance, and stemness of HCC cells in vitro as well as tumor growth in vivo The wild-type GALNT4 could modify O-linked glycosylation on EGFR and thus modulate the activity of EGFR. 28062574 0 25 from MicroRNA-9 67:76 arg1 Carcinoma 96:104 Hepatocellular Carcinoma 81:104 Hepatocellular Carcinoma 81:104 Loss of N-Acetylgalactosaminyltransferase-4 Orchestrates Oncogenic MicroRNA-9 in Hepatocellular Carcinoma. 28062574 7 26 from expression 1348:1357 arg1 cells 1366:1370 HCC cells 1362:1370 HCC cells 1362:1370 A luciferase activity assay further identified microRNA-9 (miR-9) as the crucial specific arbitrator for GALNT4 expression in HCC cells. 28062574 3 27 theme hepatocellular 607:620 arg1 carcinoma 622:630 hepatocellular carcinoma 607:630 hepatocellular carcinoma (HCC) 607:636 This study aims to evaluate the impact of GALNT4 expression on malignant transformation of hepatocellular carcinoma (HCC). 28062574 3 27 theme hepatocellular 607:620 arg1 HCC 633:635 HCC 633:635 HCC 633:635 This study aims to evaluate the impact of GALNT4 expression on malignant transformation of hepatocellular carcinoma (HCC). 28062574 10 28 theme potential 1707:1715 arg1 axis 1697:1700 the miR-9/GALNT4 axis 1680:1700 the miR-9/GALNT4 axis 1680:1700 In conclusion, this study establishes the miR-9/GALNT4 axis as a potential adverse prognostic factor and therapeutic target for HCC patients. 28062574 10 28 theme potential 1707:1715 arg1 target 1759:1764 a potential adverse prognostic factor and therapeutic target 1705:1764 a potential adverse prognostic factor and therapeutic target for HCC patients 1705:1781 In conclusion, this study establishes the miR-9/GALNT4 axis as a potential adverse prognostic factor and therapeutic target for HCC patients. 28062574 10 29 dep potential 1707:1715 arg1 factor 1736:1741 adverse prognostic factor 1717:1741 adverse prognostic factor 1717:1741 In conclusion, this study establishes the miR-9/GALNT4 axis as a potential adverse prognostic factor and therapeutic target for HCC patients. 28062574 3 30 from impact 548:553 arg1 transformation 589:602 malignant transformation 579:602 malignant transformation of hepatocellular carcinoma (HCC) 579:636 This study aims to evaluate the impact of GALNT4 expression on malignant transformation of hepatocellular carcinoma (HCC). 28062574 4 31 from level 737:741 arg1 specimens 755:763 clinical specimens 746:763 clinical specimens 746:763 Immunohistochemistry and in situ hybridization analysis were performed to assess GALNT4 and miR-9 level in clinical specimens, respectively. 28062574 1 32 theme mucin-type 223:232 arg1 O-glycosylation 234:248 mucin-type O-glycosylation 223:248 mucin-type O-glycosylation 223:248 Deregulated expression of N-acetylgalactosaminyltransferases (GALNTs), which is responsible for the initial step of mucin-type O-glycosylation, could produce abnormal truncated O-glycans and thereby exert pivotal functions during malignant transformation. 28062574 10 33 theme therapeutic 1747:1757 arg1 axis 1697:1700 the miR-9/GALNT4 axis 1680:1700 the miR-9/GALNT4 axis 1680:1700 In conclusion, this study establishes the miR-9/GALNT4 axis as a potential adverse prognostic factor and therapeutic target for HCC patients. 28062574 10 33 theme therapeutic 1747:1757 arg1 target 1759:1764 a potential adverse prognostic factor and therapeutic target 1705:1764 a potential adverse prognostic factor and therapeutic target for HCC patients 1705:1781 In conclusion, this study establishes the miR-9/GALNT4 axis as a potential adverse prognostic factor and therapeutic target for HCC patients. 28062574 1 34 theme malignant 337:345 arg1 transformation 347:360 malignant transformation 337:360 malignant transformation 337:360 Deregulated expression of N-acetylgalactosaminyltransferases (GALNTs), which is responsible for the initial step of mucin-type O-glycosylation, could produce abnormal truncated O-glycans and thereby exert pivotal functions during malignant transformation. 28062574 6 35 dep promote 1015:1021 arg1 modulate 1205:1212 modulate 1205:1212 modulate the activity of EGFR 1205:1233 Functional investigations demonstrate that repressed GALNT4 could promote migration, invasion, anoikis resistance, and stemness of HCC cells in vitro as well as tumor growth in vivo The wild-type GALNT4 could modify O-linked glycosylation on EGFR and thus modulate the activity of EGFR. 28062574 6 35 dep promote 1015:1021 arg1 modify 1158:1163 modify 1158:1163 modify O-linked glycosylation on EGFR 1158:1194 Functional investigations demonstrate that repressed GALNT4 could promote migration, invasion, anoikis resistance, and stemness of HCC cells in vitro as well as tumor growth in vivo The wild-type GALNT4 could modify O-linked glycosylation on EGFR and thus modulate the activity of EGFR. 28062574 1 36 theme N-acetylgalactosaminyltransferases 133:166 arg1 expression 119:128 Deregulated expression 107:128 Deregulated expression 107:128 Deregulated expression of N-acetylgalactosaminyltransferases (GALNTs), which is responsible for the initial step of mucin-type O-glycosylation, could produce abnormal truncated O-glycans and thereby exert pivotal functions during malignant transformation. 28062574 1 37 theme O-glycosylation 234:248 arg1 step 215:218 the initial step 203:218 the initial step of mucin-type O-glycosylation 203:248 Deregulated expression of N-acetylgalactosaminyltransferases (GALNTs), which is responsible for the initial step of mucin-type O-glycosylation, could produce abnormal truncated O-glycans and thereby exert pivotal functions during malignant transformation. 28062574 5 38 theme adverse 910:916 arg1 survival 918:925 adverse survival 910:925 adverse survival of patients with HCC 910:946 GALNT4 expression is markedly repressed in primary HCC tissues, and reduced expression of GALNT4 is significantly associated with adverse survival of patients with HCC. 28062574 8 39 theme restoring 1386:1394 arg1 expression 1403:1412 restoring GALNT4 expression 1386:1412 restoring GALNT4 expression 1386:1412 Furthermore, restoring GALNT4 expression attenuates miR-9-mediated oncogenic functions. 28062574 2 40 gly GalNAc-glycosylated 428:446 arg1 substrates 448:457 partial GalNAc-glycosylated substrates 420:457 partial GalNAc-glycosylated substrates 420:457 GALNT4 is one of the few isoforms preferring to catalyze partial GalNAc-glycosylated substrates and modify the sites not utilized by other known GALNTs. 28062574 6 41 theme EGFR 1230:1233 arg1 activity 1218:1225 the activity 1214:1225 the activity of EGFR 1214:1233 Functional investigations demonstrate that repressed GALNT4 could promote migration, invasion, anoikis resistance, and stemness of HCC cells in vitro as well as tumor growth in vivo The wild-type GALNT4 could modify O-linked glycosylation on EGFR and thus modulate the activity of EGFR. 28062574 2 42 theme other 496:500 arg1 GALNTs 508:513 other known GALNTs 496:513 other known GALNTs 496:513 GALNT4 is one of the few isoforms preferring to catalyze partial GalNAc-glycosylated substrates and modify the sites not utilized by other known GALNTs. 28062574 2 43 theme known 502:506 arg1 GALNTs 508:513 other known GALNTs 496:513 other known GALNTs 496:513 GALNT4 is one of the few isoforms preferring to catalyze partial GalNAc-glycosylated substrates and modify the sites not utilized by other known GALNTs. 28062574 4 44 from GALNT4 720:725 arg1 specimens 755:763 clinical specimens 746:763 clinical specimens 746:763 Immunohistochemistry and in situ hybridization analysis were performed to assess GALNT4 and miR-9 level in clinical specimens, respectively. 28062574 5 45 theme patients 930:937 arg1 survival 918:925 adverse survival 910:925 adverse survival of patients with HCC 910:946 GALNT4 expression is markedly repressed in primary HCC tissues, and reduced expression of GALNT4 is significantly associated with adverse survival of patients with HCC. 28062574 9 46 theme Kaplan-Meier 1461:1472 arg1 analysis 1483:1490 Kaplan-Meier survival analysis 1461:1490 Kaplan-Meier survival analysis 1461:1490 Kaplan-Meier survival analysis indicates that the miR-9/GALNT4 expression signature yields promising prognostic significance to refine the risk stratification of patients with HCC. 28062574 9 47 theme patients 1623:1630 arg1 stratification 1605:1618 the risk stratification 1596:1618 the risk stratification of patients with HCC 1596:1639 Kaplan-Meier survival analysis indicates that the miR-9/GALNT4 expression signature yields promising prognostic significance to refine the risk stratification of patients with HCC. 28062574 4 48 theme clinical 746:753 arg1 specimens 755:763 clinical specimens 746:763 clinical specimens 746:763 Immunohistochemistry and in situ hybridization analysis were performed to assess GALNT4 and miR-9 level in clinical specimens, respectively. 28062574 4 49 theme miR-9 731:735 arg1 level 737:741 miR-9 level 731:741 miR-9 level 731:741 Immunohistochemistry and in situ hybridization analysis were performed to assess GALNT4 and miR-9 level in clinical specimens, respectively. 28062574 0 50 theme Oncogenic 57:65 arg1 MicroRNA-9 67:76 Oncogenic MicroRNA-9 57:76 Oncogenic MicroRNA-9 in Hepatocellular Carcinoma 57:104 Loss of N-Acetylgalactosaminyltransferase-4 Orchestrates Oncogenic MicroRNA-9 in Hepatocellular Carcinoma. 28062574 9 51 theme survival 1474:1481 arg1 analysis 1483:1490 Kaplan-Meier survival analysis 1461:1490 Kaplan-Meier survival analysis 1461:1490 Kaplan-Meier survival analysis indicates that the miR-9/GALNT4 expression signature yields promising prognostic significance to refine the risk stratification of patients with HCC. 28062574 5 52 theme GALNT4 870:875 arg1 expression 856:865 reduced expression 848:865 reduced expression of GALNT4 848:875 GALNT4 expression is markedly repressed in primary HCC tissues, and reduced expression of GALNT4 is significantly associated with adverse survival of patients with HCC. 28062574 4 53 dep in 664:665 arg1 situ 667:670 situ 667:670 situ 667:670 Immunohistochemistry and in situ hybridization analysis were performed to assess GALNT4 and miR-9 level in clinical specimens, respectively. 28062574 7 54 theme luciferase 1238:1247 arg1 assay 1258:1262 A luciferase activity assay 1236:1262 A luciferase activity assay 1236:1262 A luciferase activity assay further identified microRNA-9 (miR-9) as the crucial specific arbitrator for GALNT4 expression in HCC cells. 28062574 1 55 theme abnormal 265:272 arg1 O-glycans 284:292 abnormal truncated O-glycans 265:292 abnormal truncated O-glycans 265:292 Deregulated expression of N-acetylgalactosaminyltransferases (GALNTs), which is responsible for the initial step of mucin-type O-glycosylation, could produce abnormal truncated O-glycans and thereby exert pivotal functions during malignant transformation. 28062574 0 56 theme Hepatocellular 81:94 arg1 Carcinoma 96:104 Hepatocellular Carcinoma 81:104 Hepatocellular Carcinoma 81:104 Loss of N-Acetylgalactosaminyltransferase-4 Orchestrates Oncogenic MicroRNA-9 in Hepatocellular Carcinoma. 28062574 6 57 theme repressed 992:1000 arg1 GALNT4 1002:1007 repressed GALNT4 992:1007 repressed GALNT4 992:1007 Functional investigations demonstrate that repressed GALNT4 could promote migration, invasion, anoikis resistance, and stemness of HCC cells in vitro as well as tumor growth in vivo The wild-type GALNT4 could modify O-linked glycosylation on EGFR and thus modulate the activity of EGFR. 28062574 7 58 theme HCC 1362:1364 arg1 cells 1366:1370 HCC cells 1362:1370 HCC cells 1362:1370 A luciferase activity assay further identified microRNA-9 (miR-9) as the crucial specific arbitrator for GALNT4 expression in HCC cells. 28062574 5 59 with patients 930:937 arg1 HCC 944:946 HCC 944:946 HCC 944:946 GALNT4 expression is markedly repressed in primary HCC tissues, and reduced expression of GALNT4 is significantly associated with adverse survival of patients with HCC. 28062574 6 60 theme anoikis 1044:1050 arg1 resistance 1052:1061 anoikis resistance 1044:1061 anoikis resistance 1044:1061 Functional investigations demonstrate that repressed GALNT4 could promote migration, invasion, anoikis resistance, and stemness of HCC cells in vitro as well as tumor growth in vivo The wild-type GALNT4 could modify O-linked glycosylation on EGFR and thus modulate the activity of EGFR. 28062574 9 61 with patients 1623:1630 arg1 HCC 1637:1639 HCC 1637:1639 HCC 1637:1639 Kaplan-Meier survival analysis indicates that the miR-9/GALNT4 expression signature yields promising prognostic significance to refine the risk stratification of patients with HCC. 28062574 3 62 theme GALNT4 558:563 arg1 expression 565:574 GALNT4 expression 558:574 GALNT4 expression 558:574 This study aims to evaluate the impact of GALNT4 expression on malignant transformation of hepatocellular carcinoma (HCC). 28062574 7 63 theme GALNT4 1341:1346 arg1 expression 1348:1357 GALNT4 expression 1341:1357 GALNT4 expression in HCC cells 1341:1370 A luciferase activity assay further identified microRNA-9 (miR-9) as the crucial specific arbitrator for GALNT4 expression in HCC cells. 28062574 1 64 dep produce 257:263 arg1 exert 306:310 exert 306:310 exert pivotal functions during malignant transformation 306:360 Deregulated expression of N-acetylgalactosaminyltransferases (GALNTs), which is responsible for the initial step of mucin-type O-glycosylation, could produce abnormal truncated O-glycans and thereby exert pivotal functions during malignant transformation. 28062574 2 65 theme isoforms 388:395 arg1 one 373:375 one 373:375 one 373:375 GALNT4 is one of the few isoforms preferring to catalyze partial GalNAc-glycosylated substrates and modify the sites not utilized by other known GALNTs. 28062574 2 65 theme isoforms 388:395 arg1 isoforms 388:395 the few isoforms 380:395 the few isoforms preferring to catalyze partial GalNAc-glycosylated substrates and modify the sites not utilized by other known GALNTs 380:513 GALNT4 is one of the few isoforms preferring to catalyze partial GalNAc-glycosylated substrates and modify the sites not utilized by other known GALNTs. 28062574 1 66 theme truncated 274:282 arg1 O-glycans 284:292 abnormal truncated O-glycans 265:292 abnormal truncated O-glycans 265:292 Deregulated expression of N-acetylgalactosaminyltransferases (GALNTs), which is responsible for the initial step of mucin-type O-glycosylation, could produce abnormal truncated O-glycans and thereby exert pivotal functions during malignant transformation. 28062574 5 67 theme GALNT4 780:785 arg1 expression 787:796 GALNT4 expression 780:796 GALNT4 expression 780:796 GALNT4 expression is markedly repressed in primary HCC tissues, and reduced expression of GALNT4 is significantly associated with adverse survival of patients with HCC. 28062574 9 68 theme promising 1552:1560 arg1 significance 1573:1584 promising prognostic significance 1552:1584 promising prognostic significance 1552:1584 Kaplan-Meier survival analysis indicates that the miR-9/GALNT4 expression signature yields promising prognostic significance to refine the risk stratification of patients with HCC. 28062574 9 69 theme prognostic 1562:1571 arg1 significance 1573:1584 promising prognostic significance 1552:1584 promising prognostic significance 1552:1584 Kaplan-Meier survival analysis indicates that the miR-9/GALNT4 expression signature yields promising prognostic significance to refine the risk stratification of patients with HCC. 28062574 2 70 theme few 384:386 arg1 isoforms 388:395 the few isoforms 380:395 the few isoforms preferring to catalyze partial GalNAc-glycosylated substrates and modify the sites not utilized by other known GALNTs 380:513 GALNT4 is one of the few isoforms preferring to catalyze partial GalNAc-glycosylated substrates and modify the sites not utilized by other known GALNTs. 28062574 8 71 theme miR-9-mediated 1425:1438 arg1 functions 1450:1458 miR-9-mediated oncogenic functions 1425:1458 miR-9-mediated oncogenic functions 1425:1458 Furthermore, restoring GALNT4 expression attenuates miR-9-mediated oncogenic functions. 28062574 6 72 theme tumor 1110:1114 arg1 growth 1116:1121 tumor growth 1110:1121 migration, invasion, anoikis resistance, and stemness of HCC cells in vitro as well as tumor growth 1023:1121 Functional investigations demonstrate that repressed GALNT4 could promote migration, invasion, anoikis resistance, and stemness of HCC cells in vitro as well as tumor growth in vivo The wild-type GALNT4 could modify O-linked glycosylation on EGFR and thus modulate the activity of EGFR. 28062574 6 73 theme wild-type 1135:1143 arg1 GALNT4 1145:1150 The wild-type GALNT4 1131:1150 The wild-type GALNT4 1131:1150 Functional investigations demonstrate that repressed GALNT4 could promote migration, invasion, anoikis resistance, and stemness of HCC cells in vitro as well as tumor growth in vivo The wild-type GALNT4 could modify O-linked glycosylation on EGFR and thus modulate the activity of EGFR. 28062574 3 74 theme malignant 579:587 arg1 transformation 589:602 malignant transformation 579:602 malignant transformation of hepatocellular carcinoma (HCC) 579:636 This study aims to evaluate the impact of GALNT4 expression on malignant transformation of hepatocellular carcinoma (HCC). 28062574 9 75 theme expression 1524:1533 arg1 signature 1535:1543 the miR-9/GALNT4 expression signature 1507:1543 the miR-9/GALNT4 expression signature 1507:1543 Kaplan-Meier survival analysis indicates that the miR-9/GALNT4 expression signature yields promising prognostic significance to refine the risk stratification of patients with HCC. 28062574 7 76 theme crucial 1309:1315 arg1 arbitrator 1326:1335 the crucial specific arbitrator 1305:1335 the crucial specific arbitrator for GALNT4 expression in HCC cells 1305:1370 A luciferase activity assay further identified microRNA-9 (miR-9) as the crucial specific arbitrator for GALNT4 expression in HCC cells. 28062574 7 76 theme crucial 1309:1315 arg1 microRNA-9 1283:1292 microRNA-9 1283:1292 microRNA-9 (miR-9) 1283:1300 A luciferase activity assay further identified microRNA-9 (miR-9) as the crucial specific arbitrator for GALNT4 expression in HCC cells. 28062574 0 77 theme N-Acetylgalactosaminyltransferase-4 8:42 arg1 Loss 0:3 Loss 0:3 Loss of N-Acetylgalactosaminyltransferase-4 0:42 Loss of N-Acetylgalactosaminyltransferase-4 Orchestrates Oncogenic MicroRNA-9 in Hepatocellular Carcinoma. 28062574 6 78 theme HCC 1080:1082 arg1 cells 1084:1088 HCC cells 1080:1088 HCC cells 1080:1088 Functional investigations demonstrate that repressed GALNT4 could promote migration, invasion, anoikis resistance, and stemness of HCC cells in vitro as well as tumor growth in vivo The wild-type GALNT4 could modify O-linked glycosylation on EGFR and thus modulate the activity of EGFR. 28062574 2 79 theme GalNAc-glycosylated 428:446 arg1 substrates 448:457 partial GalNAc-glycosylated substrates 420:457 partial GalNAc-glycosylated substrates 420:457 GALNT4 is one of the few isoforms preferring to catalyze partial GalNAc-glycosylated substrates and modify the sites not utilized by other known GALNTs. 28062574 7 80 theme specific 1317:1324 arg1 arbitrator 1326:1335 the crucial specific arbitrator 1305:1335 the crucial specific arbitrator for GALNT4 expression in HCC cells 1305:1370 A luciferase activity assay further identified microRNA-9 (miR-9) as the crucial specific arbitrator for GALNT4 expression in HCC cells. 28062574 7 80 theme specific 1317:1324 arg1 microRNA-9 1283:1292 microRNA-9 1283:1292 microRNA-9 (miR-9) 1283:1300 A luciferase activity assay further identified microRNA-9 (miR-9) as the crucial specific arbitrator for GALNT4 expression in HCC cells. 28062574 10 81 theme adverse 1717:1723 arg1 factor 1736:1741 adverse prognostic factor 1717:1741 adverse prognostic factor 1717:1741 In conclusion, this study establishes the miR-9/GALNT4 axis as a potential adverse prognostic factor and therapeutic target for HCC patients. 26343633 4 0 theme O-GlcNAc 537:544 arg1 transferase 546:556 O-GlcNAc transferase 537:556 O-GlcNAc transferase (OGT) 537:562 Despite the importance of O-GlcNAcylation in tau pathology, O-GlcNAc transferase (OGT), and an enzyme catalyzing O-GlcNAc to tau, has not been carefully investigated in the context of tau aggregation. 26343633 4 0 theme O-GlcNAc 537:544 arg1 OGT 559:561 OGT 559:561 OGT 559:561 Despite the importance of O-GlcNAcylation in tau pathology, O-GlcNAc transferase (OGT), and an enzyme catalyzing O-GlcNAc to tau, has not been carefully investigated in the context of tau aggregation. 26343633 7 1 theme O-GlcNAcase 1025:1035 arg1 G 1006:1006 Thiamet G 998:1006 Thiamet G 998:1006 Moreover, the BZX2 induced tau aggregation was efficiently reduced by the treatment of Thiamet G, an inhibitor of O-GlcNAcase (OGA). 26343633 7 1 theme O-GlcNAcase 1025:1035 arg1 inhibitor 1012:1020 an inhibitor 1009:1020 an inhibitor of O-GlcNAcase (OGA) 1009:1041 Moreover, the BZX2 induced tau aggregation was efficiently reduced by the treatment of Thiamet G, an inhibitor of O-GlcNAcase (OGA). 26343633 8 2 from OGT 1176:1178 arg1 pathology 1187:1195 tau pathology 1183:1195 tau pathology 1183:1195 Our results demonstrated the protective role of OGT in tau aggregation and also suggest the counter-regulatory mechanism of OGA and OGT in tau pathology. 26343633 1 3 theme tau 168:170 arg1 aggregation 172:182 tau aggregation 168:182 tau aggregation 168:182 Abnormal phosphorylation of tau has been considered as a key pathogenic mechanism inducing tau aggregation in multiple neurodegenerative disorders, collectively called tauopathies. 26343633 3 4 theme pathological 393:404 arg1 condition 406:414 pathological condition 393:414 pathological condition 393:414 In pathological condition, tau is de-glycosylated and becomes a substrate for kinases. 26343633 8 5 from OGA 1168:1170 arg1 pathology 1187:1195 tau pathology 1183:1195 tau pathology 1183:1195 Our results demonstrated the protective role of OGT in tau aggregation and also suggest the counter-regulatory mechanism of OGA and OGT in tau pathology. 26343633 4 6 theme tau 522:524 arg1 pathology 526:534 tau pathology 522:534 tau pathology 522:534 Despite the importance of O-GlcNAcylation in tau pathology, O-GlcNAc transferase (OGT), and an enzyme catalyzing O-GlcNAc to tau, has not been carefully investigated in the context of tau aggregation. 26343633 6 7 theme tau 894:896 arg1 aggregation 898:908 increased tau aggregation 884:908 increased tau aggregation 884:908 Upon the inhibition of OGT, tau phosphorylation increased 2.0-fold at Ser199 and 1.5-fold at Ser396, resulting in increased tau aggregation. 26343633 3 8 gly de-glycosylated 424:438 arg1 tau 417:419 tau 417:419 tau 417:419 In pathological condition, tau is de-glycosylated and becomes a substrate for kinases. 26343633 3 8 gly de-glycosylated 424:438 arg2 tau 417:419 tau 417:419 tau 417:419 In pathological condition, tau is de-glycosylated and becomes a substrate for kinases. 26343633 3 8 gly de-glycosylated 424:438 arg1 condition 406:414 pathological condition 393:414 pathological condition 393:414 In pathological condition, tau is de-glycosylated and becomes a substrate for kinases. 26343633 6 9 theme tau 798:800 arg1 phosphorylation 802:816 tau phosphorylation 798:816 tau phosphorylation 798:816 Upon the inhibition of OGT, tau phosphorylation increased 2.0-fold at Ser199 and 1.5-fold at Ser396, resulting in increased tau aggregation. 26343633 1 10 theme Abnormal 77:84 arg1 mechanism 149:157 a key pathogenic mechanism 132:157 a key pathogenic mechanism inducing tau aggregation in multiple neurodegenerative disorders, collectively called tauopathies 132:255 Abnormal phosphorylation of tau has been considered as a key pathogenic mechanism inducing tau aggregation in multiple neurodegenerative disorders, collectively called tauopathies. 26343633 1 10 theme Abnormal 77:84 arg1 phosphorylation 86:100 Abnormal phosphorylation 77:100 Abnormal phosphorylation of tau 77:107 Abnormal phosphorylation of tau has been considered as a key pathogenic mechanism inducing tau aggregation in multiple neurodegenerative disorders, collectively called tauopathies. 26343633 6 11 theme increased 884:892 arg1 aggregation 898:908 increased tau aggregation 884:908 increased tau aggregation 884:908 Upon the inhibition of OGT, tau phosphorylation increased 2.0-fold at Ser199 and 1.5-fold at Ser396, resulting in increased tau aggregation. 26343633 7 12 theme tau 938:940 arg1 aggregation 942:952 the BZX2 induced tau aggregation 921:952 the BZX2 induced tau aggregation 921:952 Moreover, the BZX2 induced tau aggregation was efficiently reduced by the treatment of Thiamet G, an inhibitor of O-GlcNAcase (OGA). 26343633 4 13 theme aggregation 665:675 arg1 context 650:656 the context 646:656 the context of tau aggregation 646:675 Despite the importance of O-GlcNAcylation in tau pathology, O-GlcNAc transferase (OGT), and an enzyme catalyzing O-GlcNAc to tau, has not been carefully investigated in the context of tau aggregation. 26343633 3 14 from de-glycosylated 424:438 arg1 condition 406:414 pathological condition 393:414 pathological condition 393:414 In pathological condition, tau is de-glycosylated and becomes a substrate for kinases. 26343633 6 15 theme OGT 793:795 arg1 inhibition 779:788 the inhibition 775:788 the inhibition of OGT 775:795 Upon the inhibition of OGT, tau phosphorylation increased 2.0-fold at Ser199 and 1.5-fold at Ser396, resulting in increased tau aggregation. 26343633 1 16 theme multiple 187:194 arg1 tauopathies 245:255 collectively called tauopathies 225:255 collectively called tauopathies 225:255 Abnormal phosphorylation of tau has been considered as a key pathogenic mechanism inducing tau aggregation in multiple neurodegenerative disorders, collectively called tauopathies. 26343633 1 16 theme multiple 187:194 arg1 disorders 214:222 multiple neurodegenerative disorders 187:222 multiple neurodegenerative disorders 187:222 Abnormal phosphorylation of tau has been considered as a key pathogenic mechanism inducing tau aggregation in multiple neurodegenerative disorders, collectively called tauopathies. 26343633 8 17 theme OGA 1168:1170 arg1 mechanism 1155:1163 the counter-regulatory mechanism 1132:1163 the counter-regulatory mechanism of OGA and OGT in tau pathology 1132:1195 Our results demonstrated the protective role of OGT in tau aggregation and also suggest the counter-regulatory mechanism of OGA and OGT in tau pathology. 26343633 7 18 theme BZX2 925:928 arg1 aggregation 942:952 the BZX2 induced tau aggregation 921:952 the BZX2 induced tau aggregation 921:952 Moreover, the BZX2 induced tau aggregation was efficiently reduced by the treatment of Thiamet G, an inhibitor of O-GlcNAcase (OGA). 26343633 1 19 theme tau 105:107 arg1 mechanism 149:157 a key pathogenic mechanism 132:157 a key pathogenic mechanism inducing tau aggregation in multiple neurodegenerative disorders, collectively called tauopathies 132:255 Abnormal phosphorylation of tau has been considered as a key pathogenic mechanism inducing tau aggregation in multiple neurodegenerative disorders, collectively called tauopathies. 26343633 1 19 theme tau 105:107 arg1 phosphorylation 86:100 Abnormal phosphorylation 77:100 Abnormal phosphorylation of tau 77:107 Abnormal phosphorylation of tau has been considered as a key pathogenic mechanism inducing tau aggregation in multiple neurodegenerative disorders, collectively called tauopathies. 26343633 1 20 theme neurodegenerative 196:212 arg1 tauopathies 245:255 collectively called tauopathies 225:255 collectively called tauopathies 225:255 Abnormal phosphorylation of tau has been considered as a key pathogenic mechanism inducing tau aggregation in multiple neurodegenerative disorders, collectively called tauopathies. 26343633 1 20 theme neurodegenerative 196:212 arg1 disorders 214:222 multiple neurodegenerative disorders 187:222 multiple neurodegenerative disorders 187:222 Abnormal phosphorylation of tau has been considered as a key pathogenic mechanism inducing tau aggregation in multiple neurodegenerative disorders, collectively called tauopathies. 26343633 0 21 theme Tau 28:30 arg1 Aggregation 32:42 Intracellular Tau Aggregation 14:42 Intracellular Tau Aggregation 14:42 Monitoring of Intracellular Tau Aggregation Regulated by OGA/OGT Inhibitors. 26343633 7 22 theme induced 930:936 arg1 aggregation 942:952 the BZX2 induced tau aggregation 921:952 the BZX2 induced tau aggregation 921:952 Moreover, the BZX2 induced tau aggregation was efficiently reduced by the treatment of Thiamet G, an inhibitor of O-GlcNAcase (OGA). 26343633 0 23 theme Intracellular 14:26 arg1 Aggregation 32:42 Intracellular Tau Aggregation 14:42 Intracellular Tau Aggregation 14:42 Monitoring of Intracellular Tau Aggregation Regulated by OGA/OGT Inhibitors. 26343633 2 24 theme O-linked 331:338 arg1 β-N-acetylglucosamine 340:360 O-linked β-N-acetylglucosamine 331:360 O-linked β-N-acetylglucosamine (O-GlcNAc) in normal brain 331:387 Recent evidence showed that tau phosphorylation sites are protected with O-linked β-N-acetylglucosamine (O-GlcNAc) in normal brain. 26343633 2 24 theme O-linked 331:338 arg1 O-GlcNAc 363:370 O-GlcNAc 363:370 O-GlcNAc 363:370 Recent evidence showed that tau phosphorylation sites are protected with O-linked β-N-acetylglucosamine (O-GlcNAc) in normal brain. 26343633 8 25 from pathology 1187:1195 arg1 mechanism 1155:1163 the counter-regulatory mechanism 1132:1163 the counter-regulatory mechanism of OGA and OGT in tau pathology 1132:1195 Our results demonstrated the protective role of OGT in tau aggregation and also suggest the counter-regulatory mechanism of OGA and OGT in tau pathology. 26343633 4 26 from importance 489:498 arg1 pathology 526:534 tau pathology 522:534 tau pathology 522:534 Despite the importance of O-GlcNAcylation in tau pathology, O-GlcNAc transferase (OGT), and an enzyme catalyzing O-GlcNAc to tau, has not been carefully investigated in the context of tau aggregation. 26343633 4 27 theme tau 661:663 arg1 aggregation 665:675 tau aggregation 661:675 tau aggregation 661:675 Despite the importance of O-GlcNAcylation in tau pathology, O-GlcNAc transferase (OGT), and an enzyme catalyzing O-GlcNAc to tau, has not been carefully investigated in the context of tau aggregation. 26343633 0 28 theme Aggregation 32:42 arg1 Monitoring 0:9 Monitoring 0:9 Monitoring of Intracellular Tau Aggregation 0:42 Monitoring of Intracellular Tau Aggregation Regulated by OGA/OGT Inhibitors. 26343633 8 29 theme tau 1183:1185 arg1 pathology 1187:1195 tau pathology 1183:1195 tau pathology 1183:1195 Our results demonstrated the protective role of OGT in tau aggregation and also suggest the counter-regulatory mechanism of OGA and OGT in tau pathology. 26343633 4 30 theme O-GlcNAcylation 503:517 arg1 importance 489:498 the importance 485:498 the importance of O-GlcNAcylation in tau pathology 485:534 Despite the importance of O-GlcNAcylation in tau pathology, O-GlcNAc transferase (OGT), and an enzyme catalyzing O-GlcNAc to tau, has not been carefully investigated in the context of tau aggregation. 26343633 2 31 theme Recent 258:263 arg1 evidence 265:272 Recent evidence 258:272 Recent evidence 258:272 Recent evidence showed that tau phosphorylation sites are protected with O-linked β-N-acetylglucosamine (O-GlcNAc) in normal brain. 26343633 1 32 theme called 238:243 arg1 tauopathies 245:255 collectively called tauopathies 225:255 collectively called tauopathies 225:255 Abnormal phosphorylation of tau has been considered as a key pathogenic mechanism inducing tau aggregation in multiple neurodegenerative disorders, collectively called tauopathies. 26343633 1 32 theme called 238:243 arg1 disorders 214:222 multiple neurodegenerative disorders 187:222 multiple neurodegenerative disorders 187:222 Abnormal phosphorylation of tau has been considered as a key pathogenic mechanism inducing tau aggregation in multiple neurodegenerative disorders, collectively called tauopathies. 26343633 0 33 theme OGA/OGT 57:63 arg1 Inhibitors 65:74 OGA/OGT Inhibitors 57:74 OGA/OGT Inhibitors 57:74 Monitoring of Intracellular Tau Aggregation Regulated by OGA/OGT Inhibitors. 26343633 2 34 link O-linked 331:338 arg1 β-N-acetylglucosamine 340:360 O-linked β-N-acetylglucosamine 331:360 O-linked β-N-acetylglucosamine (O-GlcNAc) in normal brain 331:387 Recent evidence showed that tau phosphorylation sites are protected with O-linked β-N-acetylglucosamine (O-GlcNAc) in normal brain. 26343633 2 34 link O-linked 331:338 arg1 O-GlcNAc 363:370 O-GlcNAc 363:370 O-GlcNAc 363:370 Recent evidence showed that tau phosphorylation sites are protected with O-linked β-N-acetylglucosamine (O-GlcNAc) in normal brain. 26343633 8 35 theme OGT 1092:1094 arg1 role 1084:1087 the protective role 1069:1087 the protective role of OGT in tau aggregation 1069:1113 Our results demonstrated the protective role of OGT in tau aggregation and also suggest the counter-regulatory mechanism of OGA and OGT in tau pathology. 26343633 3 36 from condition 406:414 arg1 de-glycosylated 424:438 de-glycosylated 424:438 de-glycosylated 424:438 In pathological condition, tau is de-glycosylated and becomes a substrate for kinases. 26343633 8 37 theme tau 1099:1101 arg1 aggregation 1103:1113 tau aggregation 1099:1113 tau aggregation 1099:1113 Our results demonstrated the protective role of OGT in tau aggregation and also suggest the counter-regulatory mechanism of OGA and OGT in tau pathology. 26343633 8 38 theme protective 1073:1082 arg1 role 1084:1087 the protective role 1069:1087 the protective role of OGT in tau aggregation 1069:1113 Our results demonstrated the protective role of OGT in tau aggregation and also suggest the counter-regulatory mechanism of OGA and OGT in tau pathology. 26343633 7 39 theme G 1006:1006 arg1 treatment 985:993 the treatment 981:993 the treatment of Thiamet G, an inhibitor of O-GlcNAcase (OGA) 981:1041 Moreover, the BZX2 induced tau aggregation was efficiently reduced by the treatment of Thiamet G, an inhibitor of O-GlcNAcase (OGA). 26343633 2 40 theme normal 376:381 arg1 brain 383:387 normal brain 376:387 normal brain 376:387 Recent evidence showed that tau phosphorylation sites are protected with O-linked β-N-acetylglucosamine (O-GlcNAc) in normal brain. 26343633 5 41 theme intracellular 700:712 arg1 aggregation 718:728 intracellular tau aggregation 700:728 intracellular tau aggregation regulated by BZX2, an inhibitor of OGT 700:767 Here, we investigated intracellular tau aggregation regulated by BZX2, an inhibitor of OGT. 26343633 8 42 from mechanism 1155:1163 arg1 pathology 1187:1195 tau pathology 1183:1195 tau pathology 1183:1195 Our results demonstrated the protective role of OGT in tau aggregation and also suggest the counter-regulatory mechanism of OGA and OGT in tau pathology. 26343633 2 43 theme phosphorylation 290:304 arg1 sites 306:310 tau phosphorylation sites 286:310 tau phosphorylation sites 286:310 Recent evidence showed that tau phosphorylation sites are protected with O-linked β-N-acetylglucosamine (O-GlcNAc) in normal brain. 26343633 8 44 theme counter-regulatory 1136:1153 arg1 mechanism 1155:1163 the counter-regulatory mechanism 1132:1163 the counter-regulatory mechanism of OGA and OGT in tau pathology 1132:1195 Our results demonstrated the protective role of OGT in tau aggregation and also suggest the counter-regulatory mechanism of OGA and OGT in tau pathology. 26343633 5 45 theme tau 714:716 arg1 aggregation 718:728 intracellular tau aggregation 700:728 intracellular tau aggregation regulated by BZX2, an inhibitor of OGT 700:767 Here, we investigated intracellular tau aggregation regulated by BZX2, an inhibitor of OGT. 26343633 2 46 theme tau 286:288 arg1 sites 306:310 tau phosphorylation sites 286:310 tau phosphorylation sites 286:310 Recent evidence showed that tau phosphorylation sites are protected with O-linked β-N-acetylglucosamine (O-GlcNAc) in normal brain. 26343633 1 47 theme key 134:136 arg1 mechanism 149:157 a key pathogenic mechanism 132:157 a key pathogenic mechanism inducing tau aggregation in multiple neurodegenerative disorders, collectively called tauopathies 132:255 Abnormal phosphorylation of tau has been considered as a key pathogenic mechanism inducing tau aggregation in multiple neurodegenerative disorders, collectively called tauopathies. 26343633 1 47 theme key 134:136 arg1 phosphorylation 86:100 Abnormal phosphorylation 77:100 Abnormal phosphorylation of tau 77:107 Abnormal phosphorylation of tau has been considered as a key pathogenic mechanism inducing tau aggregation in multiple neurodegenerative disorders, collectively called tauopathies. 26343633 5 48 theme OGT 765:767 arg1 inhibitor 752:760 an inhibitor 749:760 an inhibitor of OGT 749:767 Here, we investigated intracellular tau aggregation regulated by BZX2, an inhibitor of OGT. 26343633 5 48 theme OGT 765:767 arg1 BZX2 743:746 BZX2 743:746 BZX2 743:746 Here, we investigated intracellular tau aggregation regulated by BZX2, an inhibitor of OGT. 26343633 7 49 theme Thiamet 998:1004 arg1 G 1006:1006 Thiamet G 998:1006 Thiamet G 998:1006 Moreover, the BZX2 induced tau aggregation was efficiently reduced by the treatment of Thiamet G, an inhibitor of O-GlcNAcase (OGA). 26343633 7 49 theme Thiamet 998:1004 arg1 inhibitor 1012:1020 an inhibitor 1009:1020 an inhibitor of O-GlcNAcase (OGA) 1009:1041 Moreover, the BZX2 induced tau aggregation was efficiently reduced by the treatment of Thiamet G, an inhibitor of O-GlcNAcase (OGA). 26343633 1 50 theme pathogenic 138:147 arg1 mechanism 149:157 a key pathogenic mechanism 132:157 a key pathogenic mechanism inducing tau aggregation in multiple neurodegenerative disorders, collectively called tauopathies 132:255 Abnormal phosphorylation of tau has been considered as a key pathogenic mechanism inducing tau aggregation in multiple neurodegenerative disorders, collectively called tauopathies. 26343633 1 50 theme pathogenic 138:147 arg1 phosphorylation 86:100 Abnormal phosphorylation 77:100 Abnormal phosphorylation of tau 77:107 Abnormal phosphorylation of tau has been considered as a key pathogenic mechanism inducing tau aggregation in multiple neurodegenerative disorders, collectively called tauopathies. 26343633 8 51 theme OGT 1176:1178 arg1 mechanism 1155:1163 the counter-regulatory mechanism 1132:1163 the counter-regulatory mechanism of OGA and OGT in tau pathology 1132:1195 Our results demonstrated the protective role of OGT in tau aggregation and also suggest the counter-regulatory mechanism of OGA and OGT in tau pathology. 26343633 8 52 from role 1084:1087 arg1 aggregation 1103:1113 tau aggregation 1099:1113 tau aggregation 1099:1113 Our results demonstrated the protective role of OGT in tau aggregation and also suggest the counter-regulatory mechanism of OGA and OGT in tau pathology. 26343633 2 53 from β-N-acetylglucosamine 340:360 arg1 brain 383:387 normal brain 376:387 normal brain 376:387 Recent evidence showed that tau phosphorylation sites are protected with O-linked β-N-acetylglucosamine (O-GlcNAc) in normal brain. 26850058 5 0 dep in 1335:1336 arg1 vivo 1338:1341 vivo 1338:1341 vivo 1338:1341 To examine the relationship between neutralization phenotype and stably persistent infection in monkeys, we performed in vivo rectal inoculation experiments using a SHIV-MK38 molecular clone. 26850058 2 1 theme individuals 707:717 arg1 plasma 636:641 SHIV-MK38-infected plasma 617:641 SHIV-MK38-infected plasma 617:641 Here, to clarify the significance of the neutralization-resistant phenotype of SHIV in a macaque model, we initially investigated the precise neutralization phenotype of the SHIVs, including SHIV-MK38 molecular clones, using SHIV-MK38-infected plasma, a pooled plasma of human immunodeficiency virus (HIV)-infected individuals, soluble CD4 and anti-HIV-1 neutralizing mAbs, the epitopes of which were known. 26850058 2 1 theme individuals 707:717 arg1 neutralizing 747:758 anti-HIV-1 neutralizing 736:758 anti-HIV-1 neutralizing 736:758 Here, to clarify the significance of the neutralization-resistant phenotype of SHIV in a macaque model, we initially investigated the precise neutralization phenotype of the SHIVs, including SHIV-MK38 molecular clones, using SHIV-MK38-infected plasma, a pooled plasma of human immunodeficiency virus (HIV)-infected individuals, soluble CD4 and anti-HIV-1 neutralizing mAbs, the epitopes of which were known. 26850058 2 1 theme individuals 707:717 arg1 plasma 653:658 a pooled plasma 644:658 a pooled plasma of human immunodeficiency virus (HIV)-infected individuals 644:717 Here, to clarify the significance of the neutralization-resistant phenotype of SHIV in a macaque model, we initially investigated the precise neutralization phenotype of the SHIVs, including SHIV-MK38 molecular clones, using SHIV-MK38-infected plasma, a pooled plasma of human immunodeficiency virus (HIV)-infected individuals, soluble CD4 and anti-HIV-1 neutralizing mAbs, the epitopes of which were known. 26850058 2 1 theme individuals 707:717 arg1 CD4 728:730 soluble CD4 720:730 soluble CD4 720:730 Here, to clarify the significance of the neutralization-resistant phenotype of SHIV in a macaque model, we initially investigated the precise neutralization phenotype of the SHIVs, including SHIV-MK38 molecular clones, using SHIV-MK38-infected plasma, a pooled plasma of human immunodeficiency virus (HIV)-infected individuals, soluble CD4 and anti-HIV-1 neutralizing mAbs, the epitopes of which were known. 26850058 2 2 theme plasma 636:641 arg1 mAbs 760:763 SHIV-MK38-infected plasma, a pooled plasma of human immunodeficiency virus (HIV)-infected individuals, soluble CD4 and anti-HIV-1 neutralizing mAbs 617:763 SHIV-MK38-infected plasma, a pooled plasma of human immunodeficiency virus (HIV)-infected individuals, soluble CD4 and anti-HIV-1 neutralizing mAbs 617:763 Here, to clarify the significance of the neutralization-resistant phenotype of SHIV in a macaque model, we initially investigated the precise neutralization phenotype of the SHIVs, including SHIV-MK38 molecular clones, using SHIV-MK38-infected plasma, a pooled plasma of human immunodeficiency virus (HIV)-infected individuals, soluble CD4 and anti-HIV-1 neutralizing mAbs, the epitopes of which were known. 26850058 2 3 theme neutralizing 747:758 arg1 mAbs 760:763 SHIV-MK38-infected plasma, a pooled plasma of human immunodeficiency virus (HIV)-infected individuals, soluble CD4 and anti-HIV-1 neutralizing mAbs 617:763 SHIV-MK38-infected plasma, a pooled plasma of human immunodeficiency virus (HIV)-infected individuals, soluble CD4 and anti-HIV-1 neutralizing mAbs 617:763 Here, to clarify the significance of the neutralization-resistant phenotype of SHIV in a macaque model, we initially investigated the precise neutralization phenotype of the SHIVs, including SHIV-MK38 molecular clones, using SHIV-MK38-infected plasma, a pooled plasma of human immunodeficiency virus (HIV)-infected individuals, soluble CD4 and anti-HIV-1 neutralizing mAbs, the epitopes of which were known. 26850058 6 4 theme high 1546:1549 arg1 responses 1560:1568 the high antibody responses 1542:1568 the high antibody responses that occurred in the host 1542:1594 The results showed that one of three rhesus monkeys exhibited durable infection with a plasma viral load of 105 copies ml- 1 despite the high antibody responses that occurred in the host. 26850058 7 5 theme virus 1672:1676 arg1 development 1645:1655 the development 1641:1655 the development of a challenge virus 1641:1676 Whilst further improvements are required in the development of a challenge virus, it will be useful to generate a neutralization-resistant R5 tropic molecular clone of the SHIV-89.6 lineage commonly used for vaccine development - a result that can be used to explore the foundation of AIDS pathogenesis. 26850058 1 6 theme CCR5 200:203 arg1 SHIV-MK38 254:262 SHIV-MK38 254:262 SHIV-MK38 254:262 Previously, we reported that a new genetically diverse CCR5 (R5) tropic simian/human immunodeficiency virus (SHIV-MK38) adapted to rhesus monkeys became more neutralization resistant to SHIV-infected plasma than did the parental SHIV-KS661 clone. 26850058 1 6 theme CCR5 200:203 arg1 virus 247:251 a new genetically diverse CCR5 (R5) tropic simian/human immunodeficiency virus 174:251 a new genetically diverse CCR5 (R5) tropic simian/human immunodeficiency virus (SHIV-MK38) adapted to rhesus monkeys 174:289 Previously, we reported that a new genetically diverse CCR5 (R5) tropic simian/human immunodeficiency virus (SHIV-MK38) adapted to rhesus monkeys became more neutralization resistant to SHIV-infected plasma than did the parental SHIV-KS661 clone. 26850058 4 7 theme conformational 1112:1125 arg1 changes 1127:1133 conformational changes 1112:1133 conformational changes in Env associated with the net charge and potential N-linked glycosylation sites 1112:1214 Sequence analysis of the env gene suggested that the neutralization-resistant phenotype of SHIV-MK38 was acquired by conformational changes in Env associated with the net charge and potential N-linked glycosylation sites. 26850058 7 8 theme tropic 1739:1744 arg1 clone 1756:1760 a neutralization-resistant R5 tropic molecular clone 1709:1760 a neutralization-resistant R5 tropic molecular clone of the SHIV-89.6 lineage commonly used for vaccine development - a result that can be used to explore the foundation of AIDS pathogenesis 1709:1898 Whilst further improvements are required in the development of a challenge virus, it will be useful to generate a neutralization-resistant R5 tropic molecular clone of the SHIV-89.6 lineage commonly used for vaccine development - a result that can be used to explore the foundation of AIDS pathogenesis. 26850058 0 9 theme SHIV-89.6 134:142 arg1 clone 111:115 a neutralization-resistant CCR5 tropic simian/human immunodeficiency virus (SHIV-MK38) molecular clone 14:115 a neutralization-resistant CCR5 tropic simian/human immunodeficiency virus (SHIV-MK38) molecular clone 14:115 Generation of a neutralization-resistant CCR5 tropic simian/human immunodeficiency virus (SHIV-MK38) molecular clone, a derivative of SHIV-89.6. 26850058 0 9 theme SHIV-89.6 134:142 arg1 derivative 120:129 a derivative 118:129 a derivative of SHIV-89.6 118:142 Generation of a neutralization-resistant CCR5 tropic simian/human immunodeficiency virus (SHIV-MK38) molecular clone, a derivative of SHIV-89.6. 26850058 1 10 theme R5 206:207 arg1 SHIV-MK38 254:262 SHIV-MK38 254:262 SHIV-MK38 254:262 Previously, we reported that a new genetically diverse CCR5 (R5) tropic simian/human immunodeficiency virus (SHIV-MK38) adapted to rhesus monkeys became more neutralization resistant to SHIV-infected plasma than did the parental SHIV-KS661 clone. 26850058 1 10 theme R5 206:207 arg1 virus 247:251 a new genetically diverse CCR5 (R5) tropic simian/human immunodeficiency virus 174:251 a new genetically diverse CCR5 (R5) tropic simian/human immunodeficiency virus (SHIV-MK38) adapted to rhesus monkeys 174:289 Previously, we reported that a new genetically diverse CCR5 (R5) tropic simian/human immunodeficiency virus (SHIV-MK38) adapted to rhesus monkeys became more neutralization resistant to SHIV-infected plasma than did the parental SHIV-KS661 clone. 26850058 4 11 theme potential 1177:1185 arg1 sites 1210:1214 potential N-linked glycosylation sites 1177:1214 potential N-linked glycosylation sites 1177:1214 Sequence analysis of the env gene suggested that the neutralization-resistant phenotype of SHIV-MK38 was acquired by conformational changes in Env associated with the net charge and potential N-linked glycosylation sites. 26850058 5 12 from phenotype 1268:1276 arg1 monkeys 1313:1319 monkeys 1313:1319 monkeys 1313:1319 To examine the relationship between neutralization phenotype and stably persistent infection in monkeys, we performed in vivo rectal inoculation experiments using a SHIV-MK38 molecular clone. 26850058 2 13 theme anti-HIV-1 736:745 arg1 neutralizing 747:758 anti-HIV-1 neutralizing 736:758 anti-HIV-1 neutralizing 736:758 Here, to clarify the significance of the neutralization-resistant phenotype of SHIV in a macaque model, we initially investigated the precise neutralization phenotype of the SHIVs, including SHIV-MK38 molecular clones, using SHIV-MK38-infected plasma, a pooled plasma of human immunodeficiency virus (HIV)-infected individuals, soluble CD4 and anti-HIV-1 neutralizing mAbs, the epitopes of which were known. 26850058 3 14 theme neutralization 844:857 arg1 sensitivity 859:869 tier 1 neutralization sensitivity 837:869 tier 1 neutralization sensitivity 837:869 The results show that SHIV-KS661 had tier 1 neutralization sensitivity, but monkey-adapted R5 tropic SHIV-MK38 acquired neutralization resistance similar to that of tier 2 or 3 as a clone virus. 26850058 4 15 theme glycosylation 1196:1208 arg1 sites 1210:1214 potential N-linked glycosylation sites 1177:1214 potential N-linked glycosylation sites 1177:1214 Sequence analysis of the env gene suggested that the neutralization-resistant phenotype of SHIV-MK38 was acquired by conformational changes in Env associated with the net charge and potential N-linked glycosylation sites. 26850058 3 16 theme tier 837:840 arg1 sensitivity 859:869 tier 1 neutralization sensitivity 837:869 tier 1 neutralization sensitivity 837:869 The results show that SHIV-KS661 had tier 1 neutralization sensitivity, but monkey-adapted R5 tropic SHIV-MK38 acquired neutralization resistance similar to that of tier 2 or 3 as a clone virus. 26850058 0 17 theme virus 83:87 arg1 clone 111:115 a neutralization-resistant CCR5 tropic simian/human immunodeficiency virus (SHIV-MK38) molecular clone 14:115 a neutralization-resistant CCR5 tropic simian/human immunodeficiency virus (SHIV-MK38) molecular clone 14:115 Generation of a neutralization-resistant CCR5 tropic simian/human immunodeficiency virus (SHIV-MK38) molecular clone, a derivative of SHIV-89.6. 26850058 0 17 theme virus 83:87 arg1 derivative 120:129 a derivative 118:129 a derivative of SHIV-89.6 118:142 Generation of a neutralization-resistant CCR5 tropic simian/human immunodeficiency virus (SHIV-MK38) molecular clone, a derivative of SHIV-89.6. 26850058 3 18 theme monkey-adapted 876:889 arg1 SHIV-MK38 901:909 monkey-adapted R5 tropic SHIV-MK38 876:909 monkey-adapted R5 tropic SHIV-MK38 876:909 The results show that SHIV-KS661 had tier 1 neutralization sensitivity, but monkey-adapted R5 tropic SHIV-MK38 acquired neutralization resistance similar to that of tier 2 or 3 as a clone virus. 26850058 7 19 theme further 1604:1610 arg1 improvements 1612:1623 further improvements 1604:1623 further improvements 1604:1623 Whilst further improvements are required in the development of a challenge virus, it will be useful to generate a neutralization-resistant R5 tropic molecular clone of the SHIV-89.6 lineage commonly used for vaccine development - a result that can be used to explore the foundation of AIDS pathogenesis. 26850058 1 20 theme rhesus 276:281 arg1 monkeys 283:289 rhesus monkeys 276:289 rhesus monkeys 276:289 Previously, we reported that a new genetically diverse CCR5 (R5) tropic simian/human immunodeficiency virus (SHIV-MK38) adapted to rhesus monkeys became more neutralization resistant to SHIV-infected plasma than did the parental SHIV-KS661 clone. 26850058 2 21 theme soluble 720:726 arg1 CD4 728:730 soluble CD4 720:730 soluble CD4 720:730 Here, to clarify the significance of the neutralization-resistant phenotype of SHIV in a macaque model, we initially investigated the precise neutralization phenotype of the SHIVs, including SHIV-MK38 molecular clones, using SHIV-MK38-infected plasma, a pooled plasma of human immunodeficiency virus (HIV)-infected individuals, soluble CD4 and anti-HIV-1 neutralizing mAbs, the epitopes of which were known. 26850058 7 22 theme neutralization-resistant 1711:1734 arg1 clone 1756:1760 a neutralization-resistant R5 tropic molecular clone 1709:1760 a neutralization-resistant R5 tropic molecular clone of the SHIV-89.6 lineage commonly used for vaccine development - a result that can be used to explore the foundation of AIDS pathogenesis 1709:1898 Whilst further improvements are required in the development of a challenge virus, it will be useful to generate a neutralization-resistant R5 tropic molecular clone of the SHIV-89.6 lineage commonly used for vaccine development - a result that can be used to explore the foundation of AIDS pathogenesis. 26850058 2 23 theme precise 526:532 arg1 phenotype 549:557 the precise neutralization phenotype 522:557 the precise neutralization phenotype of the SHIVs, including SHIV-MK38 molecular clones 522:608 Here, to clarify the significance of the neutralization-resistant phenotype of SHIV in a macaque model, we initially investigated the precise neutralization phenotype of the SHIVs, including SHIV-MK38 molecular clones, using SHIV-MK38-infected plasma, a pooled plasma of human immunodeficiency virus (HIV)-infected individuals, soluble CD4 and anti-HIV-1 neutralizing mAbs, the epitopes of which were known. 26850058 0 24 theme molecular 101:109 arg1 clone 111:115 a neutralization-resistant CCR5 tropic simian/human immunodeficiency virus (SHIV-MK38) molecular clone 14:115 a neutralization-resistant CCR5 tropic simian/human immunodeficiency virus (SHIV-MK38) molecular clone 14:115 Generation of a neutralization-resistant CCR5 tropic simian/human immunodeficiency virus (SHIV-MK38) molecular clone, a derivative of SHIV-89.6. 26850058 0 24 theme molecular 101:109 arg1 derivative 120:129 a derivative 118:129 a derivative of SHIV-89.6 118:142 Generation of a neutralization-resistant CCR5 tropic simian/human immunodeficiency virus (SHIV-MK38) molecular clone, a derivative of SHIV-89.6. 26850058 6 25 with infection 1479:1487 arg1 load 1509:1512 a plasma viral load 1494:1512 a plasma viral load of 105 copies ml- 1 1494:1532 The results showed that one of three rhesus monkeys exhibited durable infection with a plasma viral load of 105 copies ml- 1 despite the high antibody responses that occurred in the host. 26850058 2 26 theme pooled 646:651 arg1 plasma 653:658 a pooled plasma 644:658 a pooled plasma of human immunodeficiency virus (HIV)-infected individuals 644:717 Here, to clarify the significance of the neutralization-resistant phenotype of SHIV in a macaque model, we initially investigated the precise neutralization phenotype of the SHIVs, including SHIV-MK38 molecular clones, using SHIV-MK38-infected plasma, a pooled plasma of human immunodeficiency virus (HIV)-infected individuals, soluble CD4 and anti-HIV-1 neutralizing mAbs, the epitopes of which were known. 26850058 1 27 theme parental 365:372 arg1 clone 385:389 the parental SHIV-KS661 clone 361:389 the parental SHIV-KS661 clone 361:389 Previously, we reported that a new genetically diverse CCR5 (R5) tropic simian/human immunodeficiency virus (SHIV-MK38) adapted to rhesus monkeys became more neutralization resistant to SHIV-infected plasma than did the parental SHIV-KS661 clone. 26850058 0 28 theme tropic 46:51 arg1 virus 83:87 a neutralization-resistant CCR5 tropic simian/human immunodeficiency virus 14:87 a neutralization-resistant CCR5 tropic simian/human immunodeficiency virus (SHIV-MK38) molecular clone 14:115 Generation of a neutralization-resistant CCR5 tropic simian/human immunodeficiency virus (SHIV-MK38) molecular clone, a derivative of SHIV-89.6. 26850058 3 29 theme tropic 894:899 arg1 SHIV-MK38 901:909 monkey-adapted R5 tropic SHIV-MK38 876:909 monkey-adapted R5 tropic SHIV-MK38 876:909 The results show that SHIV-KS661 had tier 1 neutralization sensitivity, but monkey-adapted R5 tropic SHIV-MK38 acquired neutralization resistance similar to that of tier 2 or 3 as a clone virus. 26850058 2 30 theme phenotype 458:466 arg1 significance 413:424 the significance 409:424 the significance of the neutralization-resistant phenotype of SHIV in a macaque model 409:493 Here, to clarify the significance of the neutralization-resistant phenotype of SHIV in a macaque model, we initially investigated the precise neutralization phenotype of the SHIVs, including SHIV-MK38 molecular clones, using SHIV-MK38-infected plasma, a pooled plasma of human immunodeficiency virus (HIV)-infected individuals, soluble CD4 and anti-HIV-1 neutralizing mAbs, the epitopes of which were known. 26850058 6 31 theme durable 1471:1477 arg1 infection 1479:1487 durable infection 1471:1487 durable infection with a plasma viral load of 105 copies ml- 1 1471:1532 The results showed that one of three rhesus monkeys exhibited durable infection with a plasma viral load of 105 copies ml- 1 despite the high antibody responses that occurred in the host. 26850058 4 32 theme gene 1024:1027 arg1 analysis 1004:1011 Sequence analysis 995:1011 Sequence analysis of the env gene 995:1027 Sequence analysis of the env gene suggested that the neutralization-resistant phenotype of SHIV-MK38 was acquired by conformational changes in Env associated with the net charge and potential N-linked glycosylation sites. 26850058 2 33 theme immunodeficiency 669:684 arg1 virus 686:690 human immunodeficiency virus 663:690 human immunodeficiency virus (HIV)-infected individuals 663:717 Here, to clarify the significance of the neutralization-resistant phenotype of SHIV in a macaque model, we initially investigated the precise neutralization phenotype of the SHIVs, including SHIV-MK38 molecular clones, using SHIV-MK38-infected plasma, a pooled plasma of human immunodeficiency virus (HIV)-infected individuals, soluble CD4 and anti-HIV-1 neutralizing mAbs, the epitopes of which were known. 26850058 2 33 theme immunodeficiency 669:684 arg1 HIV 693:695 HIV 693:695 HIV 693:695 Here, to clarify the significance of the neutralization-resistant phenotype of SHIV in a macaque model, we initially investigated the precise neutralization phenotype of the SHIVs, including SHIV-MK38 molecular clones, using SHIV-MK38-infected plasma, a pooled plasma of human immunodeficiency virus (HIV)-infected individuals, soluble CD4 and anti-HIV-1 neutralizing mAbs, the epitopes of which were known. 26850058 5 34 theme in 1335:1336 arg1 experiments 1362:1372 in vivo rectal inoculation experiments 1335:1372 in vivo rectal inoculation experiments 1335:1372 To examine the relationship between neutralization phenotype and stably persistent infection in monkeys, we performed in vivo rectal inoculation experiments using a SHIV-MK38 molecular clone. 26850058 6 35 theme monkeys 1453:1459 arg1 one 1433:1435 one 1433:1435 one 1433:1435 The results showed that one of three rhesus monkeys exhibited durable infection with a plasma viral load of 105 copies ml- 1 despite the high antibody responses that occurred in the host. 26850058 6 35 theme monkeys 1453:1459 arg1 monkeys 1453:1459 three rhesus monkeys 1440:1459 three rhesus monkeys 1440:1459 The results showed that one of three rhesus monkeys exhibited durable infection with a plasma viral load of 105 copies ml- 1 despite the high antibody responses that occurred in the host. 26850058 4 36 gly glycosylation 1196:1208 arg2 sites 1210:1214 potential N-linked glycosylation sites 1177:1214 potential N-linked glycosylation sites 1177:1214 Sequence analysis of the env gene suggested that the neutralization-resistant phenotype of SHIV-MK38 was acquired by conformational changes in Env associated with the net charge and potential N-linked glycosylation sites. 26850058 5 37 theme rectal 1343:1348 arg1 experiments 1362:1372 in vivo rectal inoculation experiments 1335:1372 in vivo rectal inoculation experiments 1335:1372 To examine the relationship between neutralization phenotype and stably persistent infection in monkeys, we performed in vivo rectal inoculation experiments using a SHIV-MK38 molecular clone. 26850058 0 38 theme CCR5 41:44 arg1 virus 83:87 a neutralization-resistant CCR5 tropic simian/human immunodeficiency virus 14:87 a neutralization-resistant CCR5 tropic simian/human immunodeficiency virus (SHIV-MK38) molecular clone 14:115 Generation of a neutralization-resistant CCR5 tropic simian/human immunodeficiency virus (SHIV-MK38) molecular clone, a derivative of SHIV-89.6. 26850058 2 39 theme SHIV 471:474 arg1 phenotype 458:466 the neutralization-resistant phenotype 429:466 the neutralization-resistant phenotype of SHIV 429:474 Here, to clarify the significance of the neutralization-resistant phenotype of SHIV in a macaque model, we initially investigated the precise neutralization phenotype of the SHIVs, including SHIV-MK38 molecular clones, using SHIV-MK38-infected plasma, a pooled plasma of human immunodeficiency virus (HIV)-infected individuals, soluble CD4 and anti-HIV-1 neutralizing mAbs, the epitopes of which were known. 26850058 3 40 contain had 833:835 arg2 sensitivity 859:869 tier 1 neutralization sensitivity 837:869 tier 1 neutralization sensitivity 837:869 The results show that SHIV-KS661 had tier 1 neutralization sensitivity, but monkey-adapted R5 tropic SHIV-MK38 acquired neutralization resistance similar to that of tier 2 or 3 as a clone virus. 26850058 3 40 contain had 833:835 arg1 SHIV-KS661 822:831 SHIV-KS661 822:831 SHIV-KS661 822:831 The results show that SHIV-KS661 had tier 1 neutralization sensitivity, but monkey-adapted R5 tropic SHIV-MK38 acquired neutralization resistance similar to that of tier 2 or 3 as a clone virus. 26850058 0 41 theme simian/human 53:64 arg1 virus 83:87 a neutralization-resistant CCR5 tropic simian/human immunodeficiency virus 14:87 a neutralization-resistant CCR5 tropic simian/human immunodeficiency virus (SHIV-MK38) molecular clone 14:115 Generation of a neutralization-resistant CCR5 tropic simian/human immunodeficiency virus (SHIV-MK38) molecular clone, a derivative of SHIV-89.6. 26850058 7 42 theme pathogenesis 1887:1898 arg1 foundation 1868:1877 the foundation 1864:1877 the foundation of AIDS pathogenesis 1864:1898 Whilst further improvements are required in the development of a challenge virus, it will be useful to generate a neutralization-resistant R5 tropic molecular clone of the SHIV-89.6 lineage commonly used for vaccine development - a result that can be used to explore the foundation of AIDS pathogenesis. 26850058 7 43 used used 1848:1851 arg2 result 1829:1834 a result 1827:1834 vaccine development - a result that can be used to explore the foundation of AIDS pathogenesis 1805:1898 Whilst further improvements are required in the development of a challenge virus, it will be useful to generate a neutralization-resistant R5 tropic molecular clone of the SHIV-89.6 lineage commonly used for vaccine development - a result that can be used to explore the foundation of AIDS pathogenesis. 26850058 5 44 theme molecular 1392:1400 arg1 clone 1402:1406 SHIV-MK38 molecular clone 1382:1406 a SHIV-MK38 molecular clone 1380:1406 To examine the relationship between neutralization phenotype and stably persistent infection in monkeys, we performed in vivo rectal inoculation experiments using a SHIV-MK38 molecular clone. 26850058 1 45 theme simian/human 217:228 arg1 SHIV-MK38 254:262 SHIV-MK38 254:262 SHIV-MK38 254:262 Previously, we reported that a new genetically diverse CCR5 (R5) tropic simian/human immunodeficiency virus (SHIV-MK38) adapted to rhesus monkeys became more neutralization resistant to SHIV-infected plasma than did the parental SHIV-KS661 clone. 26850058 1 45 theme simian/human 217:228 arg1 virus 247:251 a new genetically diverse CCR5 (R5) tropic simian/human immunodeficiency virus 174:251 a new genetically diverse CCR5 (R5) tropic simian/human immunodeficiency virus (SHIV-MK38) adapted to rhesus monkeys 174:289 Previously, we reported that a new genetically diverse CCR5 (R5) tropic simian/human immunodeficiency virus (SHIV-MK38) adapted to rhesus monkeys became more neutralization resistant to SHIV-infected plasma than did the parental SHIV-KS661 clone. 26850058 2 46 from significance 413:424 arg1 model 489:493 a macaque model 479:493 a macaque model 479:493 Here, to clarify the significance of the neutralization-resistant phenotype of SHIV in a macaque model, we initially investigated the precise neutralization phenotype of the SHIVs, including SHIV-MK38 molecular clones, using SHIV-MK38-infected plasma, a pooled plasma of human immunodeficiency virus (HIV)-infected individuals, soluble CD4 and anti-HIV-1 neutralizing mAbs, the epitopes of which were known. 26850058 6 47 theme plasma 1496:1501 arg1 load 1509:1512 a plasma viral load 1494:1512 a plasma viral load of 105 copies ml- 1 1494:1532 The results showed that one of three rhesus monkeys exhibited durable infection with a plasma viral load of 105 copies ml- 1 despite the high antibody responses that occurred in the host. 26850058 4 48 theme neutralization-resistant 1048:1071 arg1 phenotype 1073:1081 the neutralization-resistant phenotype 1044:1081 the neutralization-resistant phenotype of SHIV-MK38 1044:1094 Sequence analysis of the env gene suggested that the neutralization-resistant phenotype of SHIV-MK38 was acquired by conformational changes in Env associated with the net charge and potential N-linked glycosylation sites. 26850058 2 49 theme molecular 593:601 arg1 clones 603:608 SHIV-MK38 molecular clones 583:608 SHIV-MK38 molecular clones 583:608 Here, to clarify the significance of the neutralization-resistant phenotype of SHIV in a macaque model, we initially investigated the precise neutralization phenotype of the SHIVs, including SHIV-MK38 molecular clones, using SHIV-MK38-infected plasma, a pooled plasma of human immunodeficiency virus (HIV)-infected individuals, soluble CD4 and anti-HIV-1 neutralizing mAbs, the epitopes of which were known. 26850058 7 50 theme vaccine 1805:1811 arg1 development 1813:1823 vaccine development 1805:1823 vaccine development - a result that can be used to explore the foundation of AIDS pathogenesis 1805:1898 Whilst further improvements are required in the development of a challenge virus, it will be useful to generate a neutralization-resistant R5 tropic molecular clone of the SHIV-89.6 lineage commonly used for vaccine development - a result that can be used to explore the foundation of AIDS pathogenesis. 26850058 5 51 from infection 1300:1308 arg1 monkeys 1313:1319 monkeys 1313:1319 monkeys 1313:1319 To examine the relationship between neutralization phenotype and stably persistent infection in monkeys, we performed in vivo rectal inoculation experiments using a SHIV-MK38 molecular clone. 26850058 7 52 theme molecular 1746:1754 arg1 clone 1756:1760 a neutralization-resistant R5 tropic molecular clone 1709:1760 a neutralization-resistant R5 tropic molecular clone of the SHIV-89.6 lineage commonly used for vaccine development - a result that can be used to explore the foundation of AIDS pathogenesis 1709:1898 Whilst further improvements are required in the development of a challenge virus, it will be useful to generate a neutralization-resistant R5 tropic molecular clone of the SHIV-89.6 lineage commonly used for vaccine development - a result that can be used to explore the foundation of AIDS pathogenesis. 26850058 3 53 dep tier 965:968 arg1 2 970:970 2 970:970 2 970:970 The results show that SHIV-KS661 had tier 1 neutralization sensitivity, but monkey-adapted R5 tropic SHIV-MK38 acquired neutralization resistance similar to that of tier 2 or 3 as a clone virus. 26850058 3 53 dep tier 965:968 arg1 3 975:975 3 975:975 3 975:975 The results show that SHIV-KS661 had tier 1 neutralization sensitivity, but monkey-adapted R5 tropic SHIV-MK38 acquired neutralization resistance similar to that of tier 2 or 3 as a clone virus. 26850058 2 54 theme mAbs 760:763 arg1 epitopes 770:777 the epitopes 766:777 the epitopes 766:777 Here, to clarify the significance of the neutralization-resistant phenotype of SHIV in a macaque model, we initially investigated the precise neutralization phenotype of the SHIVs, including SHIV-MK38 molecular clones, using SHIV-MK38-infected plasma, a pooled plasma of human immunodeficiency virus (HIV)-infected individuals, soluble CD4 and anti-HIV-1 neutralizing mAbs, the epitopes of which were known. 26850058 6 55 theme antibody 1551:1558 arg1 responses 1560:1568 the high antibody responses 1542:1568 the high antibody responses that occurred in the host 1542:1594 The results showed that one of three rhesus monkeys exhibited durable infection with a plasma viral load of 105 copies ml- 1 despite the high antibody responses that occurred in the host. 26850058 1 56 theme new 176:178 arg1 SHIV-MK38 254:262 SHIV-MK38 254:262 SHIV-MK38 254:262 Previously, we reported that a new genetically diverse CCR5 (R5) tropic simian/human immunodeficiency virus (SHIV-MK38) adapted to rhesus monkeys became more neutralization resistant to SHIV-infected plasma than did the parental SHIV-KS661 clone. 26850058 1 56 theme new 176:178 arg1 virus 247:251 a new genetically diverse CCR5 (R5) tropic simian/human immunodeficiency virus 174:251 a new genetically diverse CCR5 (R5) tropic simian/human immunodeficiency virus (SHIV-MK38) adapted to rhesus monkeys 174:289 Previously, we reported that a new genetically diverse CCR5 (R5) tropic simian/human immunodeficiency virus (SHIV-MK38) adapted to rhesus monkeys became more neutralization resistant to SHIV-infected plasma than did the parental SHIV-KS661 clone. 26850058 7 57 theme challenge 1662:1670 arg1 virus 1672:1676 a challenge virus 1660:1676 a challenge virus 1660:1676 Whilst further improvements are required in the development of a challenge virus, it will be useful to generate a neutralization-resistant R5 tropic molecular clone of the SHIV-89.6 lineage commonly used for vaccine development - a result that can be used to explore the foundation of AIDS pathogenesis. 26850058 2 58 theme SHIV-MK38-infected 617:634 arg1 plasma 636:641 SHIV-MK38-infected plasma 617:641 SHIV-MK38-infected plasma 617:641 Here, to clarify the significance of the neutralization-resistant phenotype of SHIV in a macaque model, we initially investigated the precise neutralization phenotype of the SHIVs, including SHIV-MK38 molecular clones, using SHIV-MK38-infected plasma, a pooled plasma of human immunodeficiency virus (HIV)-infected individuals, soluble CD4 and anti-HIV-1 neutralizing mAbs, the epitopes of which were known. 26850058 7 59 theme lineage 1779:1785 arg1 clone 1756:1760 a neutralization-resistant R5 tropic molecular clone 1709:1760 a neutralization-resistant R5 tropic molecular clone of the SHIV-89.6 lineage commonly used for vaccine development - a result that can be used to explore the foundation of AIDS pathogenesis 1709:1898 Whilst further improvements are required in the development of a challenge virus, it will be useful to generate a neutralization-resistant R5 tropic molecular clone of the SHIV-89.6 lineage commonly used for vaccine development - a result that can be used to explore the foundation of AIDS pathogenesis. 26850058 4 60 from changes 1127:1133 arg1 Env 1138:1140 Env 1138:1140 Env 1138:1140 Sequence analysis of the env gene suggested that the neutralization-resistant phenotype of SHIV-MK38 was acquired by conformational changes in Env associated with the net charge and potential N-linked glycosylation sites. 26850058 6 61 theme ml- 1 1528:1532 arg1 load 1509:1512 a plasma viral load 1494:1512 a plasma viral load of 105 copies ml- 1 1494:1532 The results showed that one of three rhesus monkeys exhibited durable infection with a plasma viral load of 105 copies ml- 1 despite the high antibody responses that occurred in the host. 26850058 2 62 theme neutralization 534:547 arg1 phenotype 549:557 the precise neutralization phenotype 522:557 the precise neutralization phenotype of the SHIVs, including SHIV-MK38 molecular clones 522:608 Here, to clarify the significance of the neutralization-resistant phenotype of SHIV in a macaque model, we initially investigated the precise neutralization phenotype of the SHIVs, including SHIV-MK38 molecular clones, using SHIV-MK38-infected plasma, a pooled plasma of human immunodeficiency virus (HIV)-infected individuals, soluble CD4 and anti-HIV-1 neutralizing mAbs, the epitopes of which were known. 26850058 4 63 theme N-linked 1187:1194 arg1 sites 1210:1214 potential N-linked glycosylation sites 1177:1214 potential N-linked glycosylation sites 1177:1214 Sequence analysis of the env gene suggested that the neutralization-resistant phenotype of SHIV-MK38 was acquired by conformational changes in Env associated with the net charge and potential N-linked glycosylation sites. 26850058 2 64 theme -infected 697:705 arg1 individuals 707:717 human immunodeficiency virus (HIV)-infected individuals 663:717 human immunodeficiency virus (HIV)-infected individuals 663:717 Here, to clarify the significance of the neutralization-resistant phenotype of SHIV in a macaque model, we initially investigated the precise neutralization phenotype of the SHIVs, including SHIV-MK38 molecular clones, using SHIV-MK38-infected plasma, a pooled plasma of human immunodeficiency virus (HIV)-infected individuals, soluble CD4 and anti-HIV-1 neutralizing mAbs, the epitopes of which were known. 26850058 7 65 theme SHIV-89.6 1769:1777 arg1 lineage 1779:1785 the SHIV-89.6 lineage 1765:1785 the SHIV-89.6 lineage commonly used for vaccine development - a result that can be used to explore the foundation of AIDS pathogenesis 1765:1898 Whilst further improvements are required in the development of a challenge virus, it will be useful to generate a neutralization-resistant R5 tropic molecular clone of the SHIV-89.6 lineage commonly used for vaccine development - a result that can be used to explore the foundation of AIDS pathogenesis. 26850058 2 66 theme SHIVs 566:570 arg1 phenotype 549:557 the precise neutralization phenotype 522:557 the precise neutralization phenotype of the SHIVs, including SHIV-MK38 molecular clones 522:608 Here, to clarify the significance of the neutralization-resistant phenotype of SHIV in a macaque model, we initially investigated the precise neutralization phenotype of the SHIVs, including SHIV-MK38 molecular clones, using SHIV-MK38-infected plasma, a pooled plasma of human immunodeficiency virus (HIV)-infected individuals, soluble CD4 and anti-HIV-1 neutralizing mAbs, the epitopes of which were known. 26850058 4 67 theme net 1162:1164 arg1 charge 1166:1171 the net charge 1158:1171 the net charge 1158:1171 Sequence analysis of the env gene suggested that the neutralization-resistant phenotype of SHIV-MK38 was acquired by conformational changes in Env associated with the net charge and potential N-linked glycosylation sites. 26850058 1 68 theme diverse 192:198 arg1 SHIV-MK38 254:262 SHIV-MK38 254:262 SHIV-MK38 254:262 Previously, we reported that a new genetically diverse CCR5 (R5) tropic simian/human immunodeficiency virus (SHIV-MK38) adapted to rhesus monkeys became more neutralization resistant to SHIV-infected plasma than did the parental SHIV-KS661 clone. 26850058 1 68 theme diverse 192:198 arg1 virus 247:251 a new genetically diverse CCR5 (R5) tropic simian/human immunodeficiency virus 174:251 a new genetically diverse CCR5 (R5) tropic simian/human immunodeficiency virus (SHIV-MK38) adapted to rhesus monkeys 174:289 Previously, we reported that a new genetically diverse CCR5 (R5) tropic simian/human immunodeficiency virus (SHIV-MK38) adapted to rhesus monkeys became more neutralization resistant to SHIV-infected plasma than did the parental SHIV-KS661 clone. 26850058 2 69 theme CD4 728:730 arg1 mAbs 760:763 SHIV-MK38-infected plasma, a pooled plasma of human immunodeficiency virus (HIV)-infected individuals, soluble CD4 and anti-HIV-1 neutralizing mAbs 617:763 SHIV-MK38-infected plasma, a pooled plasma of human immunodeficiency virus (HIV)-infected individuals, soluble CD4 and anti-HIV-1 neutralizing mAbs 617:763 Here, to clarify the significance of the neutralization-resistant phenotype of SHIV in a macaque model, we initially investigated the precise neutralization phenotype of the SHIVs, including SHIV-MK38 molecular clones, using SHIV-MK38-infected plasma, a pooled plasma of human immunodeficiency virus (HIV)-infected individuals, soluble CD4 and anti-HIV-1 neutralizing mAbs, the epitopes of which were known. 26850058 1 70 theme SHIV-infected 331:343 arg1 plasma 345:350 SHIV-infected plasma 331:350 SHIV-infected plasma 331:350 Previously, we reported that a new genetically diverse CCR5 (R5) tropic simian/human immunodeficiency virus (SHIV-MK38) adapted to rhesus monkeys became more neutralization resistant to SHIV-infected plasma than did the parental SHIV-KS661 clone. 26850058 3 71 theme R5 891:892 arg1 SHIV-MK38 901:909 monkey-adapted R5 tropic SHIV-MK38 876:909 monkey-adapted R5 tropic SHIV-MK38 876:909 The results show that SHIV-KS661 had tier 1 neutralization sensitivity, but monkey-adapted R5 tropic SHIV-MK38 acquired neutralization resistance similar to that of tier 2 or 3 as a clone virus. 26850058 2 72 theme macaque 481:487 arg1 model 489:493 a macaque model 479:493 a macaque model 479:493 Here, to clarify the significance of the neutralization-resistant phenotype of SHIV in a macaque model, we initially investigated the precise neutralization phenotype of the SHIVs, including SHIV-MK38 molecular clones, using SHIV-MK38-infected plasma, a pooled plasma of human immunodeficiency virus (HIV)-infected individuals, soluble CD4 and anti-HIV-1 neutralizing mAbs, the epitopes of which were known. 26850058 2 73 theme human 663:667 arg1 virus 686:690 human immunodeficiency virus 663:690 human immunodeficiency virus (HIV)-infected individuals 663:717 Here, to clarify the significance of the neutralization-resistant phenotype of SHIV in a macaque model, we initially investigated the precise neutralization phenotype of the SHIVs, including SHIV-MK38 molecular clones, using SHIV-MK38-infected plasma, a pooled plasma of human immunodeficiency virus (HIV)-infected individuals, soluble CD4 and anti-HIV-1 neutralizing mAbs, the epitopes of which were known. 26850058 2 73 theme human 663:667 arg1 HIV 693:695 HIV 693:695 HIV 693:695 Here, to clarify the significance of the neutralization-resistant phenotype of SHIV in a macaque model, we initially investigated the precise neutralization phenotype of the SHIVs, including SHIV-MK38 molecular clones, using SHIV-MK38-infected plasma, a pooled plasma of human immunodeficiency virus (HIV)-infected individuals, soluble CD4 and anti-HIV-1 neutralizing mAbs, the epitopes of which were known. 26850058 5 74 theme persistent 1289:1298 arg1 infection 1300:1308 stably persistent infection 1282:1308 stably persistent infection in monkeys 1282:1319 To examine the relationship between neutralization phenotype and stably persistent infection in monkeys, we performed in vivo rectal inoculation experiments using a SHIV-MK38 molecular clone. 26850058 0 75 theme clone 111:115 arg1 Generation 0:9 Generation 0:9 Generation of a neutralization-resistant CCR5 tropic simian/human immunodeficiency virus (SHIV-MK38) molecular clone, a derivative of SHIV-89.6. 0:143 Generation of a neutralization-resistant CCR5 tropic simian/human immunodeficiency virus (SHIV-MK38) molecular clone, a derivative of SHIV-89.6. 26850058 7 76 theme R5 1736:1737 arg1 clone 1756:1760 a neutralization-resistant R5 tropic molecular clone 1709:1760 a neutralization-resistant R5 tropic molecular clone of the SHIV-89.6 lineage commonly used for vaccine development - a result that can be used to explore the foundation of AIDS pathogenesis 1709:1898 Whilst further improvements are required in the development of a challenge virus, it will be useful to generate a neutralization-resistant R5 tropic molecular clone of the SHIV-89.6 lineage commonly used for vaccine development - a result that can be used to explore the foundation of AIDS pathogenesis. 26850058 2 77 theme plasma 653:658 arg1 mAbs 760:763 SHIV-MK38-infected plasma, a pooled plasma of human immunodeficiency virus (HIV)-infected individuals, soluble CD4 and anti-HIV-1 neutralizing mAbs 617:763 SHIV-MK38-infected plasma, a pooled plasma of human immunodeficiency virus (HIV)-infected individuals, soluble CD4 and anti-HIV-1 neutralizing mAbs 617:763 Here, to clarify the significance of the neutralization-resistant phenotype of SHIV in a macaque model, we initially investigated the precise neutralization phenotype of the SHIVs, including SHIV-MK38 molecular clones, using SHIV-MK38-infected plasma, a pooled plasma of human immunodeficiency virus (HIV)-infected individuals, soluble CD4 and anti-HIV-1 neutralizing mAbs, the epitopes of which were known. 26850058 5 78 theme inoculation 1350:1360 arg1 experiments 1362:1372 in vivo rectal inoculation experiments 1335:1372 in vivo rectal inoculation experiments 1335:1372 To examine the relationship between neutralization phenotype and stably persistent infection in monkeys, we performed in vivo rectal inoculation experiments using a SHIV-MK38 molecular clone. 26850058 3 79 theme neutralization 920:933 arg1 virus 988:992 a clone virus 980:992 a clone virus 980:992 The results show that SHIV-KS661 had tier 1 neutralization sensitivity, but monkey-adapted R5 tropic SHIV-MK38 acquired neutralization resistance similar to that of tier 2 or 3 as a clone virus. 26850058 3 79 theme neutralization 920:933 arg1 resistance 935:944 neutralization resistance 920:944 neutralization resistance similar to that of tier 2 or 3 920:975 The results show that SHIV-KS661 had tier 1 neutralization sensitivity, but monkey-adapted R5 tropic SHIV-MK38 acquired neutralization resistance similar to that of tier 2 or 3 as a clone virus. 26850058 4 80 link N-linked 1187:1194 arg1 sites 1210:1214 potential N-linked glycosylation sites 1177:1214 potential N-linked glycosylation sites 1177:1214 Sequence analysis of the env gene suggested that the neutralization-resistant phenotype of SHIV-MK38 was acquired by conformational changes in Env associated with the net charge and potential N-linked glycosylation sites. 26850058 1 81 theme SHIV-KS661 374:383 arg1 clone 385:389 the parental SHIV-KS661 clone 361:389 the parental SHIV-KS661 clone 361:389 Previously, we reported that a new genetically diverse CCR5 (R5) tropic simian/human immunodeficiency virus (SHIV-MK38) adapted to rhesus monkeys became more neutralization resistant to SHIV-infected plasma than did the parental SHIV-KS661 clone. 26850058 2 82 theme neutralization-resistant 433:456 arg1 phenotype 458:466 the neutralization-resistant phenotype 429:466 the neutralization-resistant phenotype of SHIV 429:474 Here, to clarify the significance of the neutralization-resistant phenotype of SHIV in a macaque model, we initially investigated the precise neutralization phenotype of the SHIVs, including SHIV-MK38 molecular clones, using SHIV-MK38-infected plasma, a pooled plasma of human immunodeficiency virus (HIV)-infected individuals, soluble CD4 and anti-HIV-1 neutralizing mAbs, the epitopes of which were known. 26850058 2 83 theme virus 686:690 arg1 individuals 707:717 human immunodeficiency virus (HIV)-infected individuals 663:717 human immunodeficiency virus (HIV)-infected individuals 663:717 Here, to clarify the significance of the neutralization-resistant phenotype of SHIV in a macaque model, we initially investigated the precise neutralization phenotype of the SHIVs, including SHIV-MK38 molecular clones, using SHIV-MK38-infected plasma, a pooled plasma of human immunodeficiency virus (HIV)-infected individuals, soluble CD4 and anti-HIV-1 neutralizing mAbs, the epitopes of which were known. 26850058 0 84 theme neutralization-resistant 16:39 arg1 virus 83:87 a neutralization-resistant CCR5 tropic simian/human immunodeficiency virus 14:87 a neutralization-resistant CCR5 tropic simian/human immunodeficiency virus (SHIV-MK38) molecular clone 14:115 Generation of a neutralization-resistant CCR5 tropic simian/human immunodeficiency virus (SHIV-MK38) molecular clone, a derivative of SHIV-89.6. 26850058 4 85 theme env 1020:1022 arg1 gene 1024:1027 the env gene 1016:1027 the env gene 1016:1027 Sequence analysis of the env gene suggested that the neutralization-resistant phenotype of SHIV-MK38 was acquired by conformational changes in Env associated with the net charge and potential N-linked glycosylation sites. 26850058 6 86 theme rhesus 1446:1451 arg1 monkeys 1453:1459 three rhesus monkeys 1440:1459 three rhesus monkeys 1440:1459 The results showed that one of three rhesus monkeys exhibited durable infection with a plasma viral load of 105 copies ml- 1 despite the high antibody responses that occurred in the host. 26850058 3 87 theme similar 946:952 arg1 virus 988:992 a clone virus 980:992 a clone virus 980:992 The results show that SHIV-KS661 had tier 1 neutralization sensitivity, but monkey-adapted R5 tropic SHIV-MK38 acquired neutralization resistance similar to that of tier 2 or 3 as a clone virus. 26850058 3 87 theme similar 946:952 arg1 resistance 935:944 neutralization resistance 920:944 neutralization resistance similar to that of tier 2 or 3 920:975 The results show that SHIV-KS661 had tier 1 neutralization sensitivity, but monkey-adapted R5 tropic SHIV-MK38 acquired neutralization resistance similar to that of tier 2 or 3 as a clone virus. 26850058 5 88 theme neutralization 1253:1266 arg1 phenotype 1268:1276 neutralization phenotype 1253:1276 neutralization phenotype 1253:1276 To examine the relationship between neutralization phenotype and stably persistent infection in monkeys, we performed in vivo rectal inoculation experiments using a SHIV-MK38 molecular clone. 26850058 0 89 theme immunodeficiency 66:81 arg1 virus 83:87 a neutralization-resistant CCR5 tropic simian/human immunodeficiency virus 14:87 a neutralization-resistant CCR5 tropic simian/human immunodeficiency virus (SHIV-MK38) molecular clone 14:115 Generation of a neutralization-resistant CCR5 tropic simian/human immunodeficiency virus (SHIV-MK38) molecular clone, a derivative of SHIV-89.6. 26850058 7 90 theme AIDS 1882:1885 arg1 pathogenesis 1887:1898 AIDS pathogenesis 1882:1898 AIDS pathogenesis 1882:1898 Whilst further improvements are required in the development of a challenge virus, it will be useful to generate a neutralization-resistant R5 tropic molecular clone of the SHIV-89.6 lineage commonly used for vaccine development - a result that can be used to explore the foundation of AIDS pathogenesis. 26850058 4 91 theme Sequence 995:1002 arg1 analysis 1004:1011 Sequence analysis 995:1011 Sequence analysis of the env gene 995:1027 Sequence analysis of the env gene suggested that the neutralization-resistant phenotype of SHIV-MK38 was acquired by conformational changes in Env associated with the net charge and potential N-linked glycosylation sites. 26850058 1 92 dep did 357:359 arg1 than 352:355 than 352:355 than 352:355 Previously, we reported that a new genetically diverse CCR5 (R5) tropic simian/human immunodeficiency virus (SHIV-MK38) adapted to rhesus monkeys became more neutralization resistant to SHIV-infected plasma than did the parental SHIV-KS661 clone. 26850058 6 93 theme copies 1521:1526 arg1 ml- 1 1528:1532 105 copies ml- 1 1517:1532 105 copies ml- 1 1517:1532 The results showed that one of three rhesus monkeys exhibited durable infection with a plasma viral load of 105 copies ml- 1 despite the high antibody responses that occurred in the host. 26850058 7 94 dep development 1813:1823 arg1 result 1829:1834 a result 1827:1834 vaccine development - a result that can be used to explore the foundation of AIDS pathogenesis 1805:1898 Whilst further improvements are required in the development of a challenge virus, it will be useful to generate a neutralization-resistant R5 tropic molecular clone of the SHIV-89.6 lineage commonly used for vaccine development - a result that can be used to explore the foundation of AIDS pathogenesis. 26850058 1 95 theme tropic 210:215 arg1 SHIV-MK38 254:262 SHIV-MK38 254:262 SHIV-MK38 254:262 Previously, we reported that a new genetically diverse CCR5 (R5) tropic simian/human immunodeficiency virus (SHIV-MK38) adapted to rhesus monkeys became more neutralization resistant to SHIV-infected plasma than did the parental SHIV-KS661 clone. 26850058 1 95 theme tropic 210:215 arg1 virus 247:251 a new genetically diverse CCR5 (R5) tropic simian/human immunodeficiency virus 174:251 a new genetically diverse CCR5 (R5) tropic simian/human immunodeficiency virus (SHIV-MK38) adapted to rhesus monkeys 174:289 Previously, we reported that a new genetically diverse CCR5 (R5) tropic simian/human immunodeficiency virus (SHIV-MK38) adapted to rhesus monkeys became more neutralization resistant to SHIV-infected plasma than did the parental SHIV-KS661 clone. 26850058 3 96 theme clone 982:986 arg1 virus 988:992 a clone virus 980:992 a clone virus 980:992 The results show that SHIV-KS661 had tier 1 neutralization sensitivity, but monkey-adapted R5 tropic SHIV-MK38 acquired neutralization resistance similar to that of tier 2 or 3 as a clone virus. 26850058 3 96 theme clone 982:986 arg1 resistance 935:944 neutralization resistance 920:944 neutralization resistance similar to that of tier 2 or 3 920:975 The results show that SHIV-KS661 had tier 1 neutralization sensitivity, but monkey-adapted R5 tropic SHIV-MK38 acquired neutralization resistance similar to that of tier 2 or 3 as a clone virus. 26850058 4 97 theme SHIV-MK38 1086:1094 arg1 phenotype 1073:1081 the neutralization-resistant phenotype 1044:1081 the neutralization-resistant phenotype of SHIV-MK38 1044:1094 Sequence analysis of the env gene suggested that the neutralization-resistant phenotype of SHIV-MK38 was acquired by conformational changes in Env associated with the net charge and potential N-linked glycosylation sites. 26850058 6 98 theme viral 1503:1507 arg1 load 1509:1512 a plasma viral load 1494:1512 a plasma viral load of 105 copies ml- 1 1494:1532 The results showed that one of three rhesus monkeys exhibited durable infection with a plasma viral load of 105 copies ml- 1 despite the high antibody responses that occurred in the host. 26850058 1 99 theme immunodeficiency 230:245 arg1 SHIV-MK38 254:262 SHIV-MK38 254:262 SHIV-MK38 254:262 Previously, we reported that a new genetically diverse CCR5 (R5) tropic simian/human immunodeficiency virus (SHIV-MK38) adapted to rhesus monkeys became more neutralization resistant to SHIV-infected plasma than did the parental SHIV-KS661 clone. 26850058 1 99 theme immunodeficiency 230:245 arg1 virus 247:251 a new genetically diverse CCR5 (R5) tropic simian/human immunodeficiency virus 174:251 a new genetically diverse CCR5 (R5) tropic simian/human immunodeficiency virus (SHIV-MK38) adapted to rhesus monkeys 174:289 Previously, we reported that a new genetically diverse CCR5 (R5) tropic simian/human immunodeficiency virus (SHIV-MK38) adapted to rhesus monkeys became more neutralization resistant to SHIV-infected plasma than did the parental SHIV-KS661 clone. 24332980 2 0 link N-linked 364:371 arg1 glycosylation 373:385 N-linked glycosylation 364:385 N-linked glycosylation 364:385 In contrast to N-linked glycosylation, O-GlcNAcylation does not display a strict amino acid consensus sequence, although serine or threonine residues flanked by proline and valine are preferred sites of O-GlcNAcylation. 24332980 9 1 theme computational 1758:1770 arg1 methods 1783:1789 the presently available computational prediction methods 1734:1789 the presently available computational prediction methods for O-GlcNAc sites 1734:1808 Thus, our study indicates the limitations of the presently available computational prediction methods for O-GlcNAc sites and suggests that experimental validation is mandatory. 24332980 6 2 from sequence 1181:1188 arg1 located 1156:1162 located 1156:1162 located 1156:1162 However, both prediction programs revealed numerous false negative O-GlcNAc predictions when the site of modification was located in an amino acid sequence differing from the known consensus sequence. 24332980 6 2 from sequence 1181:1188 arg1 modification 1139:1150 modification 1139:1150 modification 1139:1150 However, both prediction programs revealed numerous false negative O-GlcNAc predictions when the site of modification was located in an amino acid sequence differing from the known consensus sequence. 24332980 6 2 from sequence 1181:1188 arg1 site 1131:1134 the site 1127:1134 the site of modification 1127:1150 However, both prediction programs revealed numerous false negative O-GlcNAc predictions when the site of modification was located in an amino acid sequence differing from the known consensus sequence. 24332980 1 3 theme protein-protein 284:298 arg1 interaction 300:310 protein-protein interaction 284:310 protein-protein interaction 284:310 O-GlcNAcylation is an inducible, highly dynamic and reversible posttranslational modification, which regulates numerous cellular processes such as gene expression, translation, immune reactions, protein degradation, protein-protein interaction, apoptosis, and signal transduction. 24332980 9 4 theme methods 1783:1789 arg1 limitations 1719:1729 the limitations 1715:1729 the limitations of the presently available computational prediction methods for O-GlcNAc sites 1715:1808 Thus, our study indicates the limitations of the presently available computational prediction methods for O-GlcNAc sites and suggests that experimental validation is mandatory. 24332980 5 5 theme situated 957:964 arg1 sites 951:955 O-GlcNAc sites 942:955 O-GlcNAc sites situated in an environment resembling the consensus sequence P-P-V-[ST]-T-A 942:1031 Both prediction programs efficiently identified O-GlcNAc sites situated in an environment resembling the consensus sequence P-P-V-[ST]-T-A. 24332980 9 6 theme O-GlcNAc 1795:1802 arg1 sites 1804:1808 O-GlcNAc sites 1795:1808 O-GlcNAc sites 1795:1808 Thus, our study indicates the limitations of the presently available computational prediction methods for O-GlcNAc sites and suggests that experimental validation is mandatory. 24332980 10 7 theme available 1913:1921 arg1 databases 1923:1931 available databases 1913:1931 available databases 1913:1931 Continuously update and further development of available databases will be the key to improve the performance of O-GlcNAc site prediction. 24332980 7 8 dep serine 1490:1495 arg1 residues 1511:1518 residues 1511:1518 residues 1511:1518 By searching for a common sequence motif, we found that O-GlcNAcylation of nucleocytoplasmic proteins preferably occurs at serine and threonine residues flanked downstream by proline and valine and upstream by one to two alanines followed by a stretch of serine and threonine residues. 24332980 6 9 theme prediction 1048:1057 arg1 programs 1059:1066 both prediction programs 1043:1066 both prediction programs 1043:1066 However, both prediction programs revealed numerous false negative O-GlcNAc predictions when the site of modification was located in an amino acid sequence differing from the known consensus sequence. 24332980 8 10 theme proteins 1549:1556 arg1 O-GlcNAcylation 1530:1544 O-GlcNAcylation 1530:1544 O-GlcNAcylation of proteins located in the mitochondria or in the secretory lumen 1530:1610 However, O-GlcNAcylation of proteins located in the mitochondria or in the secretory lumen occurs at different sites and does not follow a distinct consensus sequence. 24332980 3 11 theme sites 639:643 arg1 tools 621:625 computational prediction tools 596:625 computational prediction tools of O-GlcNAc sites 596:643 Based on this information, computational prediction tools of O-GlcNAc sites have been developed. 24332980 5 12 theme O-GlcNAc 942:949 arg1 sites 951:955 O-GlcNAc sites 942:955 O-GlcNAc sites situated in an environment resembling the consensus sequence P-P-V-[ST]-T-A 942:1031 Both prediction programs efficiently identified O-GlcNAc sites situated in an environment resembling the consensus sequence P-P-V-[ST]-T-A. 24332980 5 13 theme P-P-V-[ST 1018:1026 arg1 -T-A 1028:1031 the consensus sequence P-P-V-[ST]-T-A 995:1031 the consensus sequence P-P-V-[ST]-T-A 995:1031 Both prediction programs efficiently identified O-GlcNAc sites situated in an environment resembling the consensus sequence P-P-V-[ST]-T-A. 24332980 4 14 theme available 723:731 arg1 programs 753:760 two available O-GlcNAc prediction programs 719:760 two available O-GlcNAc prediction programs YinOYang 1.2 server and OGlcNAcScan 719:796 Here, we retrospectively assessed the performance of two available O-GlcNAc prediction programs YinOYang 1.2 server and OGlcNAcScan by comparing their predictions for recently discovered experimentally validated O-GlcNAc sites. 24332980 6 15 dep false 1086:1090 arg1 negative 1092:1099 negative 1092:1099 negative 1092:1099 However, both prediction programs revealed numerous false negative O-GlcNAc predictions when the site of modification was located in an amino acid sequence differing from the known consensus sequence. 24332980 4 16 theme prediction 742:751 arg1 programs 753:760 two available O-GlcNAc prediction programs 719:760 two available O-GlcNAc prediction programs YinOYang 1.2 server and OGlcNAcScan 719:796 Here, we retrospectively assessed the performance of two available O-GlcNAc prediction programs YinOYang 1.2 server and OGlcNAcScan by comparing their predictions for recently discovered experimentally validated O-GlcNAc sites. 24332980 7 17 theme proteins 1328:1335 arg1 O-GlcNAcylation 1291:1305 O-GlcNAcylation 1291:1305 O-GlcNAcylation of nucleocytoplasmic proteins 1291:1335 By searching for a common sequence motif, we found that O-GlcNAcylation of nucleocytoplasmic proteins preferably occurs at serine and threonine residues flanked downstream by proline and valine and upstream by one to two alanines followed by a stretch of serine and threonine residues. 24332980 1 18 theme numerous 179:186 arg1 transduction 335:346 signal transduction 328:346 signal transduction 328:346 O-GlcNAcylation is an inducible, highly dynamic and reversible posttranslational modification, which regulates numerous cellular processes such as gene expression, translation, immune reactions, protein degradation, protein-protein interaction, apoptosis, and signal transduction. 24332980 1 18 theme numerous 179:186 arg1 reactions 252:260 immune reactions 245:260 immune reactions 245:260 O-GlcNAcylation is an inducible, highly dynamic and reversible posttranslational modification, which regulates numerous cellular processes such as gene expression, translation, immune reactions, protein degradation, protein-protein interaction, apoptosis, and signal transduction. 24332980 1 18 theme numerous 179:186 arg1 interaction 300:310 protein-protein interaction 284:310 protein-protein interaction 284:310 O-GlcNAcylation is an inducible, highly dynamic and reversible posttranslational modification, which regulates numerous cellular processes such as gene expression, translation, immune reactions, protein degradation, protein-protein interaction, apoptosis, and signal transduction. 24332980 1 18 theme numerous 179:186 arg1 apoptosis 313:321 apoptosis 313:321 apoptosis 313:321 O-GlcNAcylation is an inducible, highly dynamic and reversible posttranslational modification, which regulates numerous cellular processes such as gene expression, translation, immune reactions, protein degradation, protein-protein interaction, apoptosis, and signal transduction. 24332980 1 18 theme numerous 179:186 arg1 expression 220:229 gene expression 215:229 gene expression 215:229 O-GlcNAcylation is an inducible, highly dynamic and reversible posttranslational modification, which regulates numerous cellular processes such as gene expression, translation, immune reactions, protein degradation, protein-protein interaction, apoptosis, and signal transduction. 24332980 1 18 theme numerous 179:186 arg1 translation 232:242 translation 232:242 translation 232:242 O-GlcNAcylation is an inducible, highly dynamic and reversible posttranslational modification, which regulates numerous cellular processes such as gene expression, translation, immune reactions, protein degradation, protein-protein interaction, apoptosis, and signal transduction. 24332980 1 18 theme numerous 179:186 arg1 degradation 271:281 protein degradation 263:281 protein degradation 263:281 O-GlcNAcylation is an inducible, highly dynamic and reversible posttranslational modification, which regulates numerous cellular processes such as gene expression, translation, immune reactions, protein degradation, protein-protein interaction, apoptosis, and signal transduction. 24332980 1 18 theme numerous 179:186 arg1 processes 197:205 numerous cellular processes 179:205 numerous cellular processes such as gene expression, translation, immune reactions, protein degradation, protein-protein interaction, apoptosis, and signal transduction 179:346 O-GlcNAcylation is an inducible, highly dynamic and reversible posttranslational modification, which regulates numerous cellular processes such as gene expression, translation, immune reactions, protein degradation, protein-protein interaction, apoptosis, and signal transduction. 24332980 6 19 theme O-GlcNAc 1101:1108 arg1 predictions 1110:1120 numerous false negative O-GlcNAc predictions 1077:1120 numerous false negative O-GlcNAc predictions when the site of modification was located in an amino acid sequence differing from the known consensus sequence 1077:1232 However, both prediction programs revealed numerous false negative O-GlcNAc predictions when the site of modification was located in an amino acid sequence differing from the known consensus sequence. 24332980 2 20 theme O-GlcNAcylation 552:566 arg1 serine 470:475 serine 470:475 serine 470:475 In contrast to N-linked glycosylation, O-GlcNAcylation does not display a strict amino acid consensus sequence, although serine or threonine residues flanked by proline and valine are preferred sites of O-GlcNAcylation. 24332980 2 20 theme O-GlcNAcylation 552:566 arg1 sites 543:547 preferred sites 533:547 preferred sites of O-GlcNAcylation 533:566 In contrast to N-linked glycosylation, O-GlcNAcylation does not display a strict amino acid consensus sequence, although serine or threonine residues flanked by proline and valine are preferred sites of O-GlcNAcylation. 24332980 2 20 theme O-GlcNAcylation 552:566 arg1 threonine 480:488 threonine 480:488 threonine 480:488 In contrast to N-linked glycosylation, O-GlcNAcylation does not display a strict amino acid consensus sequence, although serine or threonine residues flanked by proline and valine are preferred sites of O-GlcNAcylation. 24332980 2 20 theme O-GlcNAcylation 552:566 arg1 O-GlcNAcylation 552:566 O-GlcNAcylation 552:566 O-GlcNAcylation 552:566 In contrast to N-linked glycosylation, O-GlcNAcylation does not display a strict amino acid consensus sequence, although serine or threonine residues flanked by proline and valine are preferred sites of O-GlcNAcylation. 24332980 5 21 from environment 972:982 arg1 situated 957:964 situated 957:964 situated 957:964 Both prediction programs efficiently identified O-GlcNAc sites situated in an environment resembling the consensus sequence P-P-V-[ST]-T-A. 24332980 6 22 theme false 1086:1090 arg1 predictions 1110:1120 numerous false negative O-GlcNAc predictions 1077:1120 numerous false negative O-GlcNAc predictions when the site of modification was located in an amino acid sequence differing from the known consensus sequence 1077:1232 However, both prediction programs revealed numerous false negative O-GlcNAc predictions when the site of modification was located in an amino acid sequence differing from the known consensus sequence. 24332980 8 23 theme different 1622:1630 arg1 sites 1632:1636 different sites 1622:1636 different sites 1622:1636 However, O-GlcNAcylation of proteins located in the mitochondria or in the secretory lumen occurs at different sites and does not follow a distinct consensus sequence. 24332980 2 24 theme strict 423:428 arg1 sequence 451:458 a strict amino acid consensus sequence 421:458 a strict amino acid consensus sequence 421:458 In contrast to N-linked glycosylation, O-GlcNAcylation does not display a strict amino acid consensus sequence, although serine or threonine residues flanked by proline and valine are preferred sites of O-GlcNAcylation. 24332980 8 25 from mitochondria 1573:1584 arg1 located 1558:1564 located 1558:1564 located 1558:1564 However, O-GlcNAcylation of proteins located in the mitochondria or in the secretory lumen occurs at different sites and does not follow a distinct consensus sequence. 24332980 5 26 theme consensus 999:1007 arg1 -T-A 1028:1031 the consensus sequence P-P-V-[ST]-T-A 995:1031 the consensus sequence P-P-V-[ST]-T-A 995:1031 Both prediction programs efficiently identified O-GlcNAc sites situated in an environment resembling the consensus sequence P-P-V-[ST]-T-A. 24332980 6 27 theme acid 1176:1179 arg1 sequence 1181:1188 an amino acid sequence 1167:1188 an amino acid sequence differing from the known consensus sequence 1167:1232 However, both prediction programs revealed numerous false negative O-GlcNAc predictions when the site of modification was located in an amino acid sequence differing from the known consensus sequence. 24332980 2 28 dep serine 470:475 arg1 residues 490:497 residues 490:497 residues 490:497 In contrast to N-linked glycosylation, O-GlcNAcylation does not display a strict amino acid consensus sequence, although serine or threonine residues flanked by proline and valine are preferred sites of O-GlcNAcylation. 24332980 7 29 dep serine 1358:1363 arg1 residues 1379:1386 residues 1379:1386 residues 1379:1386 By searching for a common sequence motif, we found that O-GlcNAcylation of nucleocytoplasmic proteins preferably occurs at serine and threonine residues flanked downstream by proline and valine and upstream by one to two alanines followed by a stretch of serine and threonine residues. 24332980 5 30 theme prediction 899:908 arg1 programs 910:917 Both prediction programs 894:917 Both prediction programs 894:917 Both prediction programs efficiently identified O-GlcNAc sites situated in an environment resembling the consensus sequence P-P-V-[ST]-T-A. 24332980 10 31 theme site 1988:1991 arg1 prediction 1993:2002 O-GlcNAc site prediction 1979:2002 O-GlcNAc site prediction 1979:2002 Continuously update and further development of available databases will be the key to improve the performance of O-GlcNAc site prediction. 24332980 2 32 theme acid 436:439 arg1 sequence 451:458 a strict amino acid consensus sequence 421:458 a strict amino acid consensus sequence 421:458 In contrast to N-linked glycosylation, O-GlcNAcylation does not display a strict amino acid consensus sequence, although serine or threonine residues flanked by proline and valine are preferred sites of O-GlcNAcylation. 24332980 7 33 theme common 1254:1259 arg1 motif 1270:1274 a common sequence motif 1252:1274 a common sequence motif 1252:1274 By searching for a common sequence motif, we found that O-GlcNAcylation of nucleocytoplasmic proteins preferably occurs at serine and threonine residues flanked downstream by proline and valine and upstream by one to two alanines followed by a stretch of serine and threonine residues. 24332980 6 34 theme modification 1139:1150 arg1 located 1156:1162 located 1156:1162 located 1156:1162 However, both prediction programs revealed numerous false negative O-GlcNAc predictions when the site of modification was located in an amino acid sequence differing from the known consensus sequence. 24332980 6 34 theme modification 1139:1150 arg1 modification 1139:1150 modification 1139:1150 modification 1139:1150 However, both prediction programs revealed numerous false negative O-GlcNAc predictions when the site of modification was located in an amino acid sequence differing from the known consensus sequence. 24332980 6 34 theme modification 1139:1150 arg1 site 1131:1134 the site 1127:1134 the site of modification 1127:1150 However, both prediction programs revealed numerous false negative O-GlcNAc predictions when the site of modification was located in an amino acid sequence differing from the known consensus sequence. 24332980 8 35 theme consensus 1669:1677 arg1 sequence 1679:1686 a distinct consensus sequence 1658:1686 a distinct consensus sequence 1658:1686 However, O-GlcNAcylation of proteins located in the mitochondria or in the secretory lumen occurs at different sites and does not follow a distinct consensus sequence. 24332980 2 36 theme N-linked 364:371 arg1 glycosylation 373:385 N-linked glycosylation 364:385 N-linked glycosylation 364:385 In contrast to N-linked glycosylation, O-GlcNAcylation does not display a strict amino acid consensus sequence, although serine or threonine residues flanked by proline and valine are preferred sites of O-GlcNAcylation. 24332980 0 37 theme O-GlcNAc 47:54 arg1 prediction 56:65 computational O-GlcNAc prediction 33:65 computational O-GlcNAc prediction 33:65 Validation of the reliability of computational O-GlcNAc prediction. 24332980 6 38 theme consensus 1215:1223 arg1 sequence 1225:1232 the known consensus sequence 1205:1232 the known consensus sequence 1205:1232 However, both prediction programs revealed numerous false negative O-GlcNAc predictions when the site of modification was located in an amino acid sequence differing from the known consensus sequence. 24332980 4 39 theme O-GlcNAc 878:885 arg1 sites 887:891 recently discovered experimentally validated O-GlcNAc sites 833:891 recently discovered experimentally validated O-GlcNAc sites 833:891 Here, we retrospectively assessed the performance of two available O-GlcNAc prediction programs YinOYang 1.2 server and OGlcNAcScan by comparing their predictions for recently discovered experimentally validated O-GlcNAc sites. 24332980 8 40 from located 1558:1564 arg1 lumen 1606:1610 the secretory lumen 1592:1610 the secretory lumen 1592:1610 However, O-GlcNAcylation of proteins located in the mitochondria or in the secretory lumen occurs at different sites and does not follow a distinct consensus sequence. 24332980 8 40 from located 1558:1564 arg1 mitochondria 1573:1584 the mitochondria 1569:1584 the mitochondria 1569:1584 However, O-GlcNAcylation of proteins located in the mitochondria or in the secretory lumen occurs at different sites and does not follow a distinct consensus sequence. 24332980 1 41 theme protein 263:269 arg1 degradation 271:281 protein degradation 263:281 protein degradation 263:281 O-GlcNAcylation is an inducible, highly dynamic and reversible posttranslational modification, which regulates numerous cellular processes such as gene expression, translation, immune reactions, protein degradation, protein-protein interaction, apoptosis, and signal transduction. 24332980 8 42 theme secretory 1596:1604 arg1 lumen 1606:1610 the secretory lumen 1592:1610 the secretory lumen 1592:1610 However, O-GlcNAcylation of proteins located in the mitochondria or in the secretory lumen occurs at different sites and does not follow a distinct consensus sequence. 24332980 9 43 theme available 1748:1756 arg1 methods 1783:1789 the presently available computational prediction methods 1734:1789 the presently available computational prediction methods for O-GlcNAc sites 1734:1808 Thus, our study indicates the limitations of the presently available computational prediction methods for O-GlcNAc sites and suggests that experimental validation is mandatory. 24332980 10 44 theme further 1890:1896 arg1 key 1945:1947 key 1945:1947 key 1945:1947 Continuously update and further development of available databases will be the key to improve the performance of O-GlcNAc site prediction. 24332980 10 44 theme further 1890:1896 arg1 update 1879:1884 update 1879:1884 update 1879:1884 Continuously update and further development of available databases will be the key to improve the performance of O-GlcNAc site prediction. 24332980 10 44 theme further 1890:1896 arg1 development 1898:1908 further development 1890:1908 further development 1890:1908 Continuously update and further development of available databases will be the key to improve the performance of O-GlcNAc site prediction. 24332980 10 45 theme databases 1923:1931 arg1 key 1945:1947 key 1945:1947 key 1945:1947 Continuously update and further development of available databases will be the key to improve the performance of O-GlcNAc site prediction. 24332980 10 45 theme databases 1923:1931 arg1 update 1879:1884 update 1879:1884 update 1879:1884 Continuously update and further development of available databases will be the key to improve the performance of O-GlcNAc site prediction. 24332980 10 45 theme databases 1923:1931 arg1 development 1898:1908 further development 1890:1908 further development 1890:1908 Continuously update and further development of available databases will be the key to improve the performance of O-GlcNAc site prediction. 24332980 9 46 theme prediction 1772:1781 arg1 methods 1783:1789 the presently available computational prediction methods 1734:1789 the presently available computational prediction methods for O-GlcNAc sites 1734:1808 Thus, our study indicates the limitations of the presently available computational prediction methods for O-GlcNAc sites and suggests that experimental validation is mandatory. 24332980 1 47 dep inducible 90:98 arg1 reversible 120:129 reversible 120:129 reversible 120:129 O-GlcNAcylation is an inducible, highly dynamic and reversible posttranslational modification, which regulates numerous cellular processes such as gene expression, translation, immune reactions, protein degradation, protein-protein interaction, apoptosis, and signal transduction. 24332980 1 47 dep inducible 90:98 arg1 dynamic 108:114 dynamic 108:114 dynamic 108:114 O-GlcNAcylation is an inducible, highly dynamic and reversible posttranslational modification, which regulates numerous cellular processes such as gene expression, translation, immune reactions, protein degradation, protein-protein interaction, apoptosis, and signal transduction. 24332980 1 48 theme cellular 188:195 arg1 transduction 335:346 signal transduction 328:346 signal transduction 328:346 O-GlcNAcylation is an inducible, highly dynamic and reversible posttranslational modification, which regulates numerous cellular processes such as gene expression, translation, immune reactions, protein degradation, protein-protein interaction, apoptosis, and signal transduction. 24332980 1 48 theme cellular 188:195 arg1 reactions 252:260 immune reactions 245:260 immune reactions 245:260 O-GlcNAcylation is an inducible, highly dynamic and reversible posttranslational modification, which regulates numerous cellular processes such as gene expression, translation, immune reactions, protein degradation, protein-protein interaction, apoptosis, and signal transduction. 24332980 1 48 theme cellular 188:195 arg1 interaction 300:310 protein-protein interaction 284:310 protein-protein interaction 284:310 O-GlcNAcylation is an inducible, highly dynamic and reversible posttranslational modification, which regulates numerous cellular processes such as gene expression, translation, immune reactions, protein degradation, protein-protein interaction, apoptosis, and signal transduction. 24332980 1 48 theme cellular 188:195 arg1 apoptosis 313:321 apoptosis 313:321 apoptosis 313:321 O-GlcNAcylation is an inducible, highly dynamic and reversible posttranslational modification, which regulates numerous cellular processes such as gene expression, translation, immune reactions, protein degradation, protein-protein interaction, apoptosis, and signal transduction. 24332980 1 48 theme cellular 188:195 arg1 expression 220:229 gene expression 215:229 gene expression 215:229 O-GlcNAcylation is an inducible, highly dynamic and reversible posttranslational modification, which regulates numerous cellular processes such as gene expression, translation, immune reactions, protein degradation, protein-protein interaction, apoptosis, and signal transduction. 24332980 1 48 theme cellular 188:195 arg1 translation 232:242 translation 232:242 translation 232:242 O-GlcNAcylation is an inducible, highly dynamic and reversible posttranslational modification, which regulates numerous cellular processes such as gene expression, translation, immune reactions, protein degradation, protein-protein interaction, apoptosis, and signal transduction. 24332980 1 48 theme cellular 188:195 arg1 degradation 271:281 protein degradation 263:281 protein degradation 263:281 O-GlcNAcylation is an inducible, highly dynamic and reversible posttranslational modification, which regulates numerous cellular processes such as gene expression, translation, immune reactions, protein degradation, protein-protein interaction, apoptosis, and signal transduction. 24332980 1 48 theme cellular 188:195 arg1 processes 197:205 numerous cellular processes 179:205 numerous cellular processes such as gene expression, translation, immune reactions, protein degradation, protein-protein interaction, apoptosis, and signal transduction 179:346 O-GlcNAcylation is an inducible, highly dynamic and reversible posttranslational modification, which regulates numerous cellular processes such as gene expression, translation, immune reactions, protein degradation, protein-protein interaction, apoptosis, and signal transduction. 24332980 3 49 theme computational 596:608 arg1 tools 621:625 computational prediction tools 596:625 computational prediction tools of O-GlcNAc sites 596:643 Based on this information, computational prediction tools of O-GlcNAc sites have been developed. 24332980 6 50 theme numerous 1077:1084 arg1 predictions 1110:1120 numerous false negative O-GlcNAc predictions 1077:1120 numerous false negative O-GlcNAc predictions when the site of modification was located in an amino acid sequence differing from the known consensus sequence 1077:1232 However, both prediction programs revealed numerous false negative O-GlcNAc predictions when the site of modification was located in an amino acid sequence differing from the known consensus sequence. 24332980 6 51 from located 1156:1162 arg1 sequence 1181:1188 an amino acid sequence 1167:1188 an amino acid sequence differing from the known consensus sequence 1167:1232 However, both prediction programs revealed numerous false negative O-GlcNAc predictions when the site of modification was located in an amino acid sequence differing from the known consensus sequence. 24332980 1 52 theme gene 215:218 arg1 expression 220:229 gene expression 215:229 gene expression 215:229 O-GlcNAcylation is an inducible, highly dynamic and reversible posttranslational modification, which regulates numerous cellular processes such as gene expression, translation, immune reactions, protein degradation, protein-protein interaction, apoptosis, and signal transduction. 24332980 3 53 theme prediction 610:619 arg1 tools 621:625 computational prediction tools 596:625 computational prediction tools of O-GlcNAc sites 596:643 Based on this information, computational prediction tools of O-GlcNAc sites have been developed. 24332980 8 54 theme located 1558:1564 arg1 proteins 1549:1556 proteins 1549:1556 proteins located in the mitochondria or in the secretory lumen 1549:1610 However, O-GlcNAcylation of proteins located in the mitochondria or in the secretory lumen occurs at different sites and does not follow a distinct consensus sequence. 24332980 7 55 theme threonine 1501:1509 arg1 stretch 1479:1485 a stretch 1477:1485 a stretch of serine and threonine residues 1477:1518 By searching for a common sequence motif, we found that O-GlcNAcylation of nucleocytoplasmic proteins preferably occurs at serine and threonine residues flanked downstream by proline and valine and upstream by one to two alanines followed by a stretch of serine and threonine residues. 24332980 3 56 theme O-GlcNAc 630:637 arg1 sites 639:643 O-GlcNAc sites 630:643 O-GlcNAc sites 630:643 Based on this information, computational prediction tools of O-GlcNAc sites have been developed. 24332980 9 57 theme experimental 1828:1839 arg1 validation 1841:1850 experimental validation 1828:1850 experimental validation 1828:1850 Thus, our study indicates the limitations of the presently available computational prediction methods for O-GlcNAc sites and suggests that experimental validation is mandatory. 24332980 7 58 theme serine 1490:1495 arg1 stretch 1479:1485 a stretch 1477:1485 a stretch of serine and threonine residues 1477:1518 By searching for a common sequence motif, we found that O-GlcNAcylation of nucleocytoplasmic proteins preferably occurs at serine and threonine residues flanked downstream by proline and valine and upstream by one to two alanines followed by a stretch of serine and threonine residues. 24332980 5 59 theme sequence 1009:1016 arg1 -T-A 1028:1031 the consensus sequence P-P-V-[ST]-T-A 995:1031 the consensus sequence P-P-V-[ST]-T-A 995:1031 Both prediction programs efficiently identified O-GlcNAc sites situated in an environment resembling the consensus sequence P-P-V-[ST]-T-A. 24332980 4 60 theme programs 753:760 arg1 performance 704:714 the performance 700:714 the performance of two available O-GlcNAc prediction programs YinOYang 1.2 server and OGlcNAcScan 700:796 Here, we retrospectively assessed the performance of two available O-GlcNAc prediction programs YinOYang 1.2 server and OGlcNAcScan by comparing their predictions for recently discovered experimentally validated O-GlcNAc sites. 24332980 7 61 theme sequence 1261:1268 arg1 motif 1270:1274 a common sequence motif 1252:1274 a common sequence motif 1252:1274 By searching for a common sequence motif, we found that O-GlcNAcylation of nucleocytoplasmic proteins preferably occurs at serine and threonine residues flanked downstream by proline and valine and upstream by one to two alanines followed by a stretch of serine and threonine residues. 24332980 1 62 theme posttranslational 131:147 arg1 modification 149:160 an inducible, highly dynamic and reversible posttranslational modification 87:160 an inducible, highly dynamic and reversible posttranslational modification 87:160 O-GlcNAcylation is an inducible, highly dynamic and reversible posttranslational modification, which regulates numerous cellular processes such as gene expression, translation, immune reactions, protein degradation, protein-protein interaction, apoptosis, and signal transduction. 24332980 1 62 theme posttranslational 131:147 arg1 O-GlcNAcylation 68:82 O-GlcNAcylation 68:82 O-GlcNAcylation 68:82 O-GlcNAcylation is an inducible, highly dynamic and reversible posttranslational modification, which regulates numerous cellular processes such as gene expression, translation, immune reactions, protein degradation, protein-protein interaction, apoptosis, and signal transduction. 24332980 8 63 from lumen 1606:1610 arg1 located 1558:1564 located 1558:1564 located 1558:1564 However, O-GlcNAcylation of proteins located in the mitochondria or in the secretory lumen occurs at different sites and does not follow a distinct consensus sequence. 24332980 7 64 dep two 1452:1454 arg1 to 1449:1450 to 1449:1450 to 1449:1450 By searching for a common sequence motif, we found that O-GlcNAcylation of nucleocytoplasmic proteins preferably occurs at serine and threonine residues flanked downstream by proline and valine and upstream by one to two alanines followed by a stretch of serine and threonine residues. 24332980 6 65 located located 1156:1162 arg2 modification 1139:1150 modification 1139:1150 modification 1139:1150 However, both prediction programs revealed numerous false negative O-GlcNAc predictions when the site of modification was located in an amino acid sequence differing from the known consensus sequence. 24332980 6 65 located located 1156:1162 arg2 site 1131:1134 the site 1127:1134 the site of modification 1127:1150 However, both prediction programs revealed numerous false negative O-GlcNAc predictions when the site of modification was located in an amino acid sequence differing from the known consensus sequence. 24332980 6 65 located located 1156:1162 arg2 located 1156:1162 located 1156:1162 located 1156:1162 However, both prediction programs revealed numerous false negative O-GlcNAc predictions when the site of modification was located in an amino acid sequence differing from the known consensus sequence. 24332980 6 65 located located 1156:1162 arg1 sequence 1181:1188 an amino acid sequence 1167:1188 an amino acid sequence differing from the known consensus sequence 1167:1232 However, both prediction programs revealed numerous false negative O-GlcNAc predictions when the site of modification was located in an amino acid sequence differing from the known consensus sequence. 24332980 7 66 theme nucleocytoplasmic 1310:1326 arg1 proteins 1328:1335 nucleocytoplasmic proteins 1310:1335 nucleocytoplasmic proteins 1310:1335 By searching for a common sequence motif, we found that O-GlcNAcylation of nucleocytoplasmic proteins preferably occurs at serine and threonine residues flanked downstream by proline and valine and upstream by one to two alanines followed by a stretch of serine and threonine residues. 24332980 5 67 from situated 957:964 arg1 environment 972:982 an environment 969:982 an environment resembling the consensus sequence P-P-V-[ST]-T-A 969:1031 Both prediction programs efficiently identified O-GlcNAc sites situated in an environment resembling the consensus sequence P-P-V-[ST]-T-A. 24332980 4 68 theme O-GlcNAc 733:740 arg1 programs 753:760 two available O-GlcNAc prediction programs 719:760 two available O-GlcNAc prediction programs YinOYang 1.2 server and OGlcNAcScan 719:796 Here, we retrospectively assessed the performance of two available O-GlcNAc prediction programs YinOYang 1.2 server and OGlcNAcScan by comparing their predictions for recently discovered experimentally validated O-GlcNAc sites. 24332980 2 69 dep glycosylation 373:385 arg1 contrast 352:359 contrast 352:359 contrast 352:359 In contrast to N-linked glycosylation, O-GlcNAcylation does not display a strict amino acid consensus sequence, although serine or threonine residues flanked by proline and valine are preferred sites of O-GlcNAcylation. 24332980 2 70 theme preferred 533:541 arg1 serine 470:475 serine 470:475 serine 470:475 In contrast to N-linked glycosylation, O-GlcNAcylation does not display a strict amino acid consensus sequence, although serine or threonine residues flanked by proline and valine are preferred sites of O-GlcNAcylation. 24332980 2 70 theme preferred 533:541 arg1 sites 543:547 preferred sites 533:547 preferred sites of O-GlcNAcylation 533:566 In contrast to N-linked glycosylation, O-GlcNAcylation does not display a strict amino acid consensus sequence, although serine or threonine residues flanked by proline and valine are preferred sites of O-GlcNAcylation. 24332980 2 70 theme preferred 533:541 arg1 threonine 480:488 threonine 480:488 threonine 480:488 In contrast to N-linked glycosylation, O-GlcNAcylation does not display a strict amino acid consensus sequence, although serine or threonine residues flanked by proline and valine are preferred sites of O-GlcNAcylation. 24332980 2 70 theme preferred 533:541 arg1 O-GlcNAcylation 552:566 O-GlcNAcylation 552:566 O-GlcNAcylation 552:566 In contrast to N-linked glycosylation, O-GlcNAcylation does not display a strict amino acid consensus sequence, although serine or threonine residues flanked by proline and valine are preferred sites of O-GlcNAcylation. 24332980 1 71 theme inducible 90:98 arg1 modification 149:160 an inducible, highly dynamic and reversible posttranslational modification 87:160 an inducible, highly dynamic and reversible posttranslational modification 87:160 O-GlcNAcylation is an inducible, highly dynamic and reversible posttranslational modification, which regulates numerous cellular processes such as gene expression, translation, immune reactions, protein degradation, protein-protein interaction, apoptosis, and signal transduction. 24332980 1 71 theme inducible 90:98 arg1 O-GlcNAcylation 68:82 O-GlcNAcylation 68:82 O-GlcNAcylation 68:82 O-GlcNAcylation is an inducible, highly dynamic and reversible posttranslational modification, which regulates numerous cellular processes such as gene expression, translation, immune reactions, protein degradation, protein-protein interaction, apoptosis, and signal transduction. 24332980 6 72 theme amino 1170:1174 arg1 sequence 1181:1188 an amino acid sequence 1167:1188 an amino acid sequence differing from the known consensus sequence 1167:1232 However, both prediction programs revealed numerous false negative O-GlcNAc predictions when the site of modification was located in an amino acid sequence differing from the known consensus sequence. 24332980 0 73 theme reliability 18:28 arg1 Validation 0:9 Validation 0:9 Validation of the reliability of computational O-GlcNAc prediction 0:65 Validation of the reliability of computational O-GlcNAc prediction. 24332980 8 74 theme distinct 1660:1667 arg1 sequence 1679:1686 a distinct consensus sequence 1658:1686 a distinct consensus sequence 1658:1686 However, O-GlcNAcylation of proteins located in the mitochondria or in the secretory lumen occurs at different sites and does not follow a distinct consensus sequence. 24332980 10 75 theme prediction 1993:2002 arg1 performance 1964:1974 the performance 1960:1974 the performance of O-GlcNAc site prediction 1960:2002 Continuously update and further development of available databases will be the key to improve the performance of O-GlcNAc site prediction. 24332980 2 76 theme consensus 441:449 arg1 sequence 451:458 a strict amino acid consensus sequence 421:458 a strict amino acid consensus sequence 421:458 In contrast to N-linked glycosylation, O-GlcNAcylation does not display a strict amino acid consensus sequence, although serine or threonine residues flanked by proline and valine are preferred sites of O-GlcNAcylation. 24332980 0 77 theme computational 33:45 arg1 prediction 56:65 computational O-GlcNAc prediction 33:65 computational O-GlcNAc prediction 33:65 Validation of the reliability of computational O-GlcNAc prediction. 24332980 10 78 theme O-GlcNAc 1979:1986 arg1 prediction 1993:2002 O-GlcNAc site prediction 1979:2002 O-GlcNAc site prediction 1979:2002 Continuously update and further development of available databases will be the key to improve the performance of O-GlcNAc site prediction. 24332980 2 79 theme amino 430:434 arg1 sequence 451:458 a strict amino acid consensus sequence 421:458 a strict amino acid consensus sequence 421:458 In contrast to N-linked glycosylation, O-GlcNAcylation does not display a strict amino acid consensus sequence, although serine or threonine residues flanked by proline and valine are preferred sites of O-GlcNAcylation. 24332980 0 80 theme prediction 56:65 arg1 reliability 18:28 the reliability 14:28 the reliability of computational O-GlcNAc prediction 14:65 Validation of the reliability of computational O-GlcNAc prediction. 24332980 1 81 theme signal 328:333 arg1 transduction 335:346 signal transduction 328:346 signal transduction 328:346 O-GlcNAcylation is an inducible, highly dynamic and reversible posttranslational modification, which regulates numerous cellular processes such as gene expression, translation, immune reactions, protein degradation, protein-protein interaction, apoptosis, and signal transduction. 24332980 4 82 theme discovered 842:851 arg1 sites 887:891 recently discovered experimentally validated O-GlcNAc sites 833:891 recently discovered experimentally validated O-GlcNAc sites 833:891 Here, we retrospectively assessed the performance of two available O-GlcNAc prediction programs YinOYang 1.2 server and OGlcNAcScan by comparing their predictions for recently discovered experimentally validated O-GlcNAc sites. 24332980 1 83 theme immune 245:250 arg1 reactions 252:260 immune reactions 245:260 immune reactions 245:260 O-GlcNAcylation is an inducible, highly dynamic and reversible posttranslational modification, which regulates numerous cellular processes such as gene expression, translation, immune reactions, protein degradation, protein-protein interaction, apoptosis, and signal transduction. 24332980 6 84 theme known 1209:1213 arg1 sequence 1225:1232 the known consensus sequence 1205:1232 the known consensus sequence 1205:1232 However, both prediction programs revealed numerous false negative O-GlcNAc predictions when the site of modification was located in an amino acid sequence differing from the known consensus sequence. 24332980 4 85 theme validated 868:876 arg1 sites 887:891 recently discovered experimentally validated O-GlcNAc sites 833:891 recently discovered experimentally validated O-GlcNAc sites 833:891 Here, we retrospectively assessed the performance of two available O-GlcNAc prediction programs YinOYang 1.2 server and OGlcNAcScan by comparing their predictions for recently discovered experimentally validated O-GlcNAc sites. 27922006 8 0 theme ganglioside 1150:1160 arg1 binding 1162:1168 trans ganglioside binding 1144:1168 trans ganglioside binding 1144:1168 The combination of trans ganglioside binding and cis homodimerization explains how MAG maintains the myelin-axon spacing and provides a mechanism for MAG-mediated bi-directional signalling. 27922006 1 1 gly glycoprotein 94:105 arg1 glycoprotein 94:105 Myelin-associated glycoprotein 76:105 Myelin-associated glycoprotein (MAG) 76:111 Myelin-associated glycoprotein (MAG) is a myelin-expressed cell-adhesion and bi-directional signalling molecule. 27922006 1 1 gly glycoprotein 94:105 arg1 cell-adhesion 135:147 a myelin-expressed cell-adhesion 116:147 a myelin-expressed cell-adhesion 116:147 Myelin-associated glycoprotein (MAG) is a myelin-expressed cell-adhesion and bi-directional signalling molecule. 27922006 1 1 gly glycoprotein 94:105 arg1 MAG 108:110 MAG 108:110 MAG 108:110 Myelin-associated glycoprotein (MAG) is a myelin-expressed cell-adhesion and bi-directional signalling molecule. 27922006 4 2 dep domains 594:600 arg1 Ig4 602:604 Ig4 602:604 Ig4 602:604 We present crystal structures of the MAG full ectodomain, which reveal an extended conformation of five Ig domains and a homodimeric arrangement involving membrane-proximal domains Ig4 and Ig5. 27922006 4 2 dep domains 594:600 arg1 domains 594:600 membrane-proximal domains 576:600 membrane-proximal domains Ig4 and Ig5 576:612 We present crystal structures of the MAG full ectodomain, which reveal an extended conformation of five Ig domains and a homodimeric arrangement involving membrane-proximal domains Ig4 and Ig5. 27922006 4 2 dep domains 594:600 arg1 Ig5 610:612 Ig5 610:612 Ig5 610:612 We present crystal structures of the MAG full ectodomain, which reveal an extended conformation of five Ig domains and a homodimeric arrangement involving membrane-proximal domains Ig4 and Ig5. 27922006 8 3 theme myelin-axon 1226:1236 arg1 spacing 1238:1244 the myelin-axon spacing 1222:1244 the myelin-axon spacing 1222:1244 The combination of trans ganglioside binding and cis homodimerization explains how MAG maintains the myelin-axon spacing and provides a mechanism for MAG-mediated bi-directional signalling. 27922006 8 4 theme cis 1174:1176 arg1 homodimerization 1178:1193 cis homodimerization 1174:1193 cis homodimerization 1174:1193 The combination of trans ganglioside binding and cis homodimerization explains how MAG maintains the myelin-axon spacing and provides a mechanism for MAG-mediated bi-directional signalling. 27922006 6 5 from C-mannosylation 854:868 arg1 glycosylation 795:807 identified-N-linked glycosylation 775:807 identified-N-linked glycosylation 775:807 Two post-translational modifications were identified-N-linked glycosylation at the dimerization interface and tryptophan C-mannosylation proximal to the ganglioside binding site-that appear to have regulatory functions. 27922006 4 6 theme arrangement 554:564 arg1 conformation 504:515 an extended conformation 492:515 an extended conformation of five Ig domains and a homodimeric arrangement involving membrane-proximal domains Ig4 and Ig5 492:612 We present crystal structures of the MAG full ectodomain, which reveal an extended conformation of five Ig domains and a homodimeric arrangement involving membrane-proximal domains Ig4 and Ig5. 27922006 2 7 theme myelin 333:338 arg1 formation 340:348 myelin formation 333:348 myelin formation 333:348 MAG maintains the myelin-axon spacing by interacting with specific neuronal glycolipids (gangliosides), inhibits axon regeneration and controls myelin formation. 27922006 7 8 theme carbohydrate 1042:1053 arg1 recognition 1055:1065 carbohydrate recognition 1042:1065 carbohydrate recognition 1042:1065 Structure-guided mutations and neurite outgrowth assays demonstrate MAG dimerization and carbohydrate recognition are essential for its regeneration-inhibiting properties. 27922006 8 9 theme trans 1144:1148 arg1 binding 1162:1168 trans ganglioside binding 1144:1168 trans ganglioside binding 1144:1168 The combination of trans ganglioside binding and cis homodimerization explains how MAG maintains the myelin-axon spacing and provides a mechanism for MAG-mediated bi-directional signalling. 27922006 4 10 theme Ig 525:526 arg1 domains 528:534 five Ig domains 520:534 five Ig domains 520:534 We present crystal structures of the MAG full ectodomain, which reveal an extended conformation of five Ig domains and a homodimeric arrangement involving membrane-proximal domains Ig4 and Ig5. 27922006 7 11 dep demonstrate 1009:1019 arg1 essential 1071:1079 essential 1071:1079 essential 1071:1079 Structure-guided mutations and neurite outgrowth assays demonstrate MAG dimerization and carbohydrate recognition are essential for its regeneration-inhibiting properties. 27922006 4 12 theme full 462:465 arg1 ectodomain 467:476 the MAG full ectodomain 454:476 the MAG full ectodomain 454:476 We present crystal structures of the MAG full ectodomain, which reveal an extended conformation of five Ig domains and a homodimeric arrangement involving membrane-proximal domains Ig4 and Ig5. 27922006 1 13 theme Myelin-associated 76:92 arg1 glycoprotein 94:105 Myelin-associated glycoprotein 76:105 Myelin-associated glycoprotein (MAG) 76:111 Myelin-associated glycoprotein (MAG) is a myelin-expressed cell-adhesion and bi-directional signalling molecule. 27922006 1 13 theme Myelin-associated 76:92 arg1 cell-adhesion 135:147 a myelin-expressed cell-adhesion 116:147 a myelin-expressed cell-adhesion 116:147 Myelin-associated glycoprotein (MAG) is a myelin-expressed cell-adhesion and bi-directional signalling molecule. 27922006 1 13 theme Myelin-associated 76:92 arg1 MAG 108:110 MAG 108:110 MAG 108:110 Myelin-associated glycoprotein (MAG) is a myelin-expressed cell-adhesion and bi-directional signalling molecule. 27922006 7 14 theme MAG 1021:1023 arg1 dimerization 1025:1036 MAG dimerization 1021:1036 MAG dimerization 1021:1036 Structure-guided mutations and neurite outgrowth assays demonstrate MAG dimerization and carbohydrate recognition are essential for its regeneration-inhibiting properties. 27922006 5 15 theme axonal 698:703 arg1 gangliosides 705:716 axonal gangliosides 698:716 axonal gangliosides 698:716 MAG-oligosaccharide complex structures and biophysical assays show how MAG engages axonal gangliosides at domain Ig1. 27922006 4 16 theme MAG 458:460 arg1 ectodomain 467:476 the MAG full ectodomain 454:476 the MAG full ectodomain 454:476 We present crystal structures of the MAG full ectodomain, which reveal an extended conformation of five Ig domains and a homodimeric arrangement involving membrane-proximal domains Ig4 and Ig5. 27922006 6 17 from interface 829:837 arg1 glycosylation 795:807 identified-N-linked glycosylation 775:807 identified-N-linked glycosylation 775:807 Two post-translational modifications were identified-N-linked glycosylation at the dimerization interface and tryptophan C-mannosylation proximal to the ganglioside binding site-that appear to have regulatory functions. 27922006 6 18 theme dimerization 816:827 arg1 interface 829:837 dimerization interface 816:837 dimerization interface 816:837 Two post-translational modifications were identified-N-linked glycosylation at the dimerization interface and tryptophan C-mannosylation proximal to the ganglioside binding site-that appear to have regulatory functions. 27922006 8 19 theme binding 1162:1168 arg1 combination 1129:1139 The combination 1125:1139 The combination of trans ganglioside binding and cis homodimerization 1125:1193 The combination of trans ganglioside binding and cis homodimerization explains how MAG maintains the myelin-axon spacing and provides a mechanism for MAG-mediated bi-directional signalling. 27922006 6 20 contain have 926:929 arg1 modifications 756:768 Two post-translational modifications 733:768 Two post-translational modifications were identified-N-linked glycosylation at the dimerization interface and tryptophan C-mannosylation proximal to the ganglioside binding site-that 733:914 Two post-translational modifications were identified-N-linked glycosylation at the dimerization interface and tryptophan C-mannosylation proximal to the ganglioside binding site-that appear to have regulatory functions. 27922006 6 20 contain have 926:929 arg2 functions 942:950 regulatory functions 931:950 regulatory functions 931:950 Two post-translational modifications were identified-N-linked glycosylation at the dimerization interface and tryptophan C-mannosylation proximal to the ganglioside binding site-that appear to have regulatory functions. 27922006 6 21 link identified-N-linked 775:793 arg1 glycosylation 795:807 identified-N-linked glycosylation 775:807 identified-N-linked glycosylation 775:807 Two post-translational modifications were identified-N-linked glycosylation at the dimerization interface and tryptophan C-mannosylation proximal to the ganglioside binding site-that appear to have regulatory functions. 27922006 4 22 theme domains 528:534 arg1 conformation 504:515 an extended conformation 492:515 an extended conformation of five Ig domains and a homodimeric arrangement involving membrane-proximal domains Ig4 and Ig5 492:612 We present crystal structures of the MAG full ectodomain, which reveal an extended conformation of five Ig domains and a homodimeric arrangement involving membrane-proximal domains Ig4 and Ig5. 27922006 8 23 theme MAG-mediated 1275:1286 arg1 signalling 1303:1312 MAG-mediated bi-directional signalling 1275:1312 MAG-mediated bi-directional signalling 1275:1312 The combination of trans ganglioside binding and cis homodimerization explains how MAG maintains the myelin-axon spacing and provides a mechanism for MAG-mediated bi-directional signalling. 27922006 0 24 theme Structural 0:9 arg1 basis 11:15 Structural basis 0:15 Structural basis of myelin-associated glycoprotein adhesion and signalling 0:73 Structural basis of myelin-associated glycoprotein adhesion and signalling. 27922006 5 25 theme domain 721:726 arg1 Ig1 728:730 domain Ig1 721:730 domain Ig1 721:730 MAG-oligosaccharide complex structures and biophysical assays show how MAG engages axonal gangliosides at domain Ig1. 27922006 5 26 theme biophysical 658:668 arg1 assays 670:675 biophysical assays 658:675 biophysical assays 658:675 MAG-oligosaccharide complex structures and biophysical assays show how MAG engages axonal gangliosides at domain Ig1. 27922006 7 27 theme neurite 984:990 arg1 outgrowth 992:1000 neurite outgrowth 984:1000 neurite outgrowth assays 984:1007 Structure-guided mutations and neurite outgrowth assays demonstrate MAG dimerization and carbohydrate recognition are essential for its regeneration-inhibiting properties. 27922006 6 28 gly glycosylation 795:807 arg1 C-mannosylation 854:868 tryptophan C-mannosylation 843:868 tryptophan C-mannosylation 843:868 Two post-translational modifications were identified-N-linked glycosylation at the dimerization interface and tryptophan C-mannosylation proximal to the ganglioside binding site-that appear to have regulatory functions. 27922006 6 28 gly glycosylation 795:807 arg2 interface 829:837 dimerization interface 816:837 dimerization interface 816:837 Two post-translational modifications were identified-N-linked glycosylation at the dimerization interface and tryptophan C-mannosylation proximal to the ganglioside binding site-that appear to have regulatory functions. 27922006 6 28 gly glycosylation 795:807 arg2 C-mannosylation 854:868 tryptophan C-mannosylation 843:868 tryptophan C-mannosylation 843:868 Two post-translational modifications were identified-N-linked glycosylation at the dimerization interface and tryptophan C-mannosylation proximal to the ganglioside binding site-that appear to have regulatory functions. 27922006 6 28 gly glycosylation 795:807 arg1 interface 829:837 dimerization interface 816:837 dimerization interface 816:837 Two post-translational modifications were identified-N-linked glycosylation at the dimerization interface and tryptophan C-mannosylation proximal to the ganglioside binding site-that appear to have regulatory functions. 27922006 0 29 theme myelin-associated 20:36 arg1 adhesion 51:58 myelin-associated glycoprotein adhesion 20:58 myelin-associated glycoprotein adhesion 20:58 Structural basis of myelin-associated glycoprotein adhesion and signalling. 27922006 6 30 dep interface 829:837 arg1 the 812:814 the 812:814 the 812:814 Two post-translational modifications were identified-N-linked glycosylation at the dimerization interface and tryptophan C-mannosylation proximal to the ganglioside binding site-that appear to have regulatory functions. 27922006 2 31 theme neuronal 256:263 arg1 gangliosides 278:289 gangliosides 278:289 gangliosides 278:289 MAG maintains the myelin-axon spacing by interacting with specific neuronal glycolipids (gangliosides), inhibits axon regeneration and controls myelin formation. 27922006 2 31 theme neuronal 256:263 arg1 glycolipids 265:275 specific neuronal glycolipids 247:275 specific neuronal glycolipids (gangliosides) 247:290 MAG maintains the myelin-axon spacing by interacting with specific neuronal glycolipids (gangliosides), inhibits axon regeneration and controls myelin formation. 27922006 6 32 theme identified-N-linked 775:793 arg1 glycosylation 795:807 identified-N-linked glycosylation 775:807 identified-N-linked glycosylation 775:807 Two post-translational modifications were identified-N-linked glycosylation at the dimerization interface and tryptophan C-mannosylation proximal to the ganglioside binding site-that appear to have regulatory functions. 27922006 8 33 theme bi-directional 1288:1301 arg1 signalling 1303:1312 MAG-mediated bi-directional signalling 1275:1312 MAG-mediated bi-directional signalling 1275:1312 The combination of trans ganglioside binding and cis homodimerization explains how MAG maintains the myelin-axon spacing and provides a mechanism for MAG-mediated bi-directional signalling. 27922006 4 34 theme extended 495:502 arg1 conformation 504:515 an extended conformation 492:515 an extended conformation of five Ig domains and a homodimeric arrangement involving membrane-proximal domains Ig4 and Ig5 492:612 We present crystal structures of the MAG full ectodomain, which reveal an extended conformation of five Ig domains and a homodimeric arrangement involving membrane-proximal domains Ig4 and Ig5. 27922006 0 35 theme adhesion 51:58 arg1 basis 11:15 Structural basis 0:15 Structural basis of myelin-associated glycoprotein adhesion and signalling 0:73 Structural basis of myelin-associated glycoprotein adhesion and signalling. 27922006 2 36 theme myelin-axon 207:217 arg1 spacing 219:225 the myelin-axon spacing 203:225 the myelin-axon spacing 203:225 MAG maintains the myelin-axon spacing by interacting with specific neuronal glycolipids (gangliosides), inhibits axon regeneration and controls myelin formation. 27922006 0 37 theme glycoprotein 38:49 arg1 adhesion 51:58 myelin-associated glycoprotein adhesion 20:58 myelin-associated glycoprotein adhesion 20:58 Structural basis of myelin-associated glycoprotein adhesion and signalling. 27922006 6 38 theme binding 898:904 arg1 site-that 906:914 the ganglioside binding site-that 882:914 the ganglioside binding site-that 882:914 Two post-translational modifications were identified-N-linked glycosylation at the dimerization interface and tryptophan C-mannosylation proximal to the ganglioside binding site-that appear to have regulatory functions. 27922006 0 39 theme signalling 64:73 arg1 basis 11:15 Structural basis 0:15 Structural basis of myelin-associated glycoprotein adhesion and signalling 0:73 Structural basis of myelin-associated glycoprotein adhesion and signalling. 27922006 4 40 theme membrane-proximal 576:592 arg1 Ig4 602:604 Ig4 602:604 Ig4 602:604 We present crystal structures of the MAG full ectodomain, which reveal an extended conformation of five Ig domains and a homodimeric arrangement involving membrane-proximal domains Ig4 and Ig5. 27922006 4 40 theme membrane-proximal 576:592 arg1 domains 594:600 membrane-proximal domains 576:600 membrane-proximal domains Ig4 and Ig5 576:612 We present crystal structures of the MAG full ectodomain, which reveal an extended conformation of five Ig domains and a homodimeric arrangement involving membrane-proximal domains Ig4 and Ig5. 27922006 4 40 theme membrane-proximal 576:592 arg1 Ig5 610:612 Ig5 610:612 Ig5 610:612 We present crystal structures of the MAG full ectodomain, which reveal an extended conformation of five Ig domains and a homodimeric arrangement involving membrane-proximal domains Ig4 and Ig5. 27922006 7 41 theme outgrowth 992:1000 arg1 assays 1002:1007 neurite outgrowth assays 984:1007 neurite outgrowth assays 984:1007 Structure-guided mutations and neurite outgrowth assays demonstrate MAG dimerization and carbohydrate recognition are essential for its regeneration-inhibiting properties. 27922006 6 42 theme ganglioside 886:896 arg1 site-that 906:914 the ganglioside binding site-that 882:914 the ganglioside binding site-that 882:914 Two post-translational modifications were identified-N-linked glycosylation at the dimerization interface and tryptophan C-mannosylation proximal to the ganglioside binding site-that appear to have regulatory functions. 27922006 1 43 theme myelin-expressed 118:133 arg1 glycoprotein 94:105 Myelin-associated glycoprotein 76:105 Myelin-associated glycoprotein (MAG) 76:111 Myelin-associated glycoprotein (MAG) is a myelin-expressed cell-adhesion and bi-directional signalling molecule. 27922006 1 43 theme myelin-expressed 118:133 arg1 cell-adhesion 135:147 a myelin-expressed cell-adhesion 116:147 a myelin-expressed cell-adhesion 116:147 Myelin-associated glycoprotein (MAG) is a myelin-expressed cell-adhesion and bi-directional signalling molecule. 27922006 2 44 theme specific 247:254 arg1 gangliosides 278:289 gangliosides 278:289 gangliosides 278:289 MAG maintains the myelin-axon spacing by interacting with specific neuronal glycolipids (gangliosides), inhibits axon regeneration and controls myelin formation. 27922006 2 44 theme specific 247:254 arg1 glycolipids 265:275 specific neuronal glycolipids 247:275 specific neuronal glycolipids (gangliosides) 247:290 MAG maintains the myelin-axon spacing by interacting with specific neuronal glycolipids (gangliosides), inhibits axon regeneration and controls myelin formation. 27922006 4 45 theme ectodomain 467:476 arg1 structures 440:449 crystal structures 432:449 crystal structures 432:449 We present crystal structures of the MAG full ectodomain, which reveal an extended conformation of five Ig domains and a homodimeric arrangement involving membrane-proximal domains Ig4 and Ig5. 27922006 5 46 theme MAG-oligosaccharide 615:633 arg1 structures 643:652 MAG-oligosaccharide complex structures 615:652 MAG-oligosaccharide complex structures 615:652 MAG-oligosaccharide complex structures and biophysical assays show how MAG engages axonal gangliosides at domain Ig1. 27922006 6 47 theme post-translational 737:754 arg1 modifications 756:768 Two post-translational modifications 733:768 Two post-translational modifications were identified-N-linked glycosylation at the dimerization interface and tryptophan C-mannosylation proximal to the ganglioside binding site-that 733:914 Two post-translational modifications were identified-N-linked glycosylation at the dimerization interface and tryptophan C-mannosylation proximal to the ganglioside binding site-that appear to have regulatory functions. 27922006 4 48 theme crystal 432:438 arg1 structures 440:449 crystal structures 432:449 crystal structures 432:449 We present crystal structures of the MAG full ectodomain, which reveal an extended conformation of five Ig domains and a homodimeric arrangement involving membrane-proximal domains Ig4 and Ig5. 27922006 0 49 gly glycoprotein 38:49 arg1 glycoprotein 38:49 myelin-associated glycoprotein adhesion 20:58 myelin-associated glycoprotein adhesion 20:58 Structural basis of myelin-associated glycoprotein adhesion and signalling. 27922006 2 50 theme axon 302:305 arg1 regeneration 307:318 axon regeneration 302:318 axon regeneration 302:318 MAG maintains the myelin-axon spacing by interacting with specific neuronal glycolipids (gangliosides), inhibits axon regeneration and controls myelin formation. 27922006 5 51 theme complex 635:641 arg1 structures 643:652 MAG-oligosaccharide complex structures 615:652 MAG-oligosaccharide complex structures 615:652 MAG-oligosaccharide complex structures and biophysical assays show how MAG engages axonal gangliosides at domain Ig1. 27922006 8 52 theme homodimerization 1178:1193 arg1 combination 1129:1139 The combination 1125:1139 The combination of trans ganglioside binding and cis homodimerization 1125:1193 The combination of trans ganglioside binding and cis homodimerization explains how MAG maintains the myelin-axon spacing and provides a mechanism for MAG-mediated bi-directional signalling. 27922006 7 53 theme regeneration-inhibiting 1089:1111 arg1 properties 1113:1122 its regeneration-inhibiting properties 1085:1122 its regeneration-inhibiting properties 1085:1122 Structure-guided mutations and neurite outgrowth assays demonstrate MAG dimerization and carbohydrate recognition are essential for its regeneration-inhibiting properties. 27922006 6 54 theme proximal 870:877 arg1 interface 829:837 dimerization interface 816:837 dimerization interface 816:837 Two post-translational modifications were identified-N-linked glycosylation at the dimerization interface and tryptophan C-mannosylation proximal to the ganglioside binding site-that appear to have regulatory functions. 27922006 1 55 theme bi-directional 153:166 arg1 molecule 179:186 bi-directional signalling molecule 153:186 bi-directional signalling molecule 153:186 Myelin-associated glycoprotein (MAG) is a myelin-expressed cell-adhesion and bi-directional signalling molecule. 27922006 6 56 theme regulatory 931:940 arg1 functions 942:950 regulatory functions 931:950 regulatory functions 931:950 Two post-translational modifications were identified-N-linked glycosylation at the dimerization interface and tryptophan C-mannosylation proximal to the ganglioside binding site-that appear to have regulatory functions. 27922006 3 57 theme MAG 377:379 arg1 adhesion 381:388 MAG adhesion 377:388 MAG adhesion 377:388 The mechanisms underlying MAG adhesion and signalling are unresolved. 27922006 7 58 theme Structure-guided 953:968 arg1 mutations 970:978 Structure-guided mutations 953:978 Structure-guided mutations 953:978 Structure-guided mutations and neurite outgrowth assays demonstrate MAG dimerization and carbohydrate recognition are essential for its regeneration-inhibiting properties. 27922006 1 59 theme signalling 168:177 arg1 molecule 179:186 bi-directional signalling molecule 153:186 bi-directional signalling molecule 153:186 Myelin-associated glycoprotein (MAG) is a myelin-expressed cell-adhesion and bi-directional signalling molecule. 27922006 4 60 theme homodimeric 542:552 arg1 arrangement 554:564 a homodimeric arrangement 540:564 a homodimeric arrangement involving membrane-proximal domains Ig4 and Ig5 540:612 We present crystal structures of the MAG full ectodomain, which reveal an extended conformation of five Ig domains and a homodimeric arrangement involving membrane-proximal domains Ig4 and Ig5. 27922006 6 61 theme tryptophan 843:852 arg1 C-mannosylation 854:868 tryptophan C-mannosylation 843:868 tryptophan C-mannosylation 843:868 Two post-translational modifications were identified-N-linked glycosylation at the dimerization interface and tryptophan C-mannosylation proximal to the ganglioside binding site-that appear to have regulatory functions. 24173317 6 0 theme specific 1146:1153 arg1 proteomics 1155:1164 proteomics and modification specific proteomics 1118:1164 proteomics 1155:1164 Combining proteomics and modification specific proteomics we identified a total of 5105 proteins whereof 57% contained transmembrane domains or signal peptides. 24173317 3 1 theme post-translational 525:542 arg1 glycosylation 586:598 glycosylation 586:598 glycosylation 586:598 Membrane-associated proteins are very important in cellular signaling and recognition, and their function and activity are frequently regulated by post-translational modifications such as phosphorylation and glycosylation. 24173317 3 1 theme post-translational 525:542 arg1 modifications 544:556 post-translational modifications 525:556 post-translational modifications such as phosphorylation and glycosylation 525:598 Membrane-associated proteins are very important in cellular signaling and recognition, and their function and activity are frequently regulated by post-translational modifications such as phosphorylation and glycosylation. 24173317 3 1 theme post-translational 525:542 arg1 phosphorylation 566:580 phosphorylation 566:580 phosphorylation 566:580 Membrane-associated proteins are very important in cellular signaling and recognition, and their function and activity are frequently regulated by post-translational modifications such as phosphorylation and glycosylation. 24173317 3 2 from recognition 452:462 arg1 important 416:424 important 416:424 important 416:424 Membrane-associated proteins are very important in cellular signaling and recognition, and their function and activity are frequently regulated by post-translational modifications such as phosphorylation and glycosylation. 24173317 9 3 theme novel 1741:1745 arg1 markers 1709:1715 potential NSC markers 1695:1715 potential NSC markers 1695:1715 In the latter group of proteins, we could identify potential NSC markers as Crumbs 2 and several novel proteins. 24173317 9 3 theme novel 1741:1745 arg1 proteins 1747:1754 several novel proteins 1733:1754 several novel proteins 1733:1754 In the latter group of proteins, we could identify potential NSC markers as Crumbs 2 and several novel proteins. 24173317 7 4 theme N-linked 1467:1474 arg1 glycopeptides 1476:1488 1810 unique formerly sialylated N-linked glycopeptides 1435:1488 1810 unique formerly sialylated N-linked glycopeptides 1435:1488 The enrichment strategy yielded a total of 10,087 phosphorylated peptides in which 78% of phosphopeptides were identified with ≥99% confidence in site assignment and 1810 unique formerly sialylated N-linked glycopeptides. 24173317 6 5 theme proteins 1196:1203 arg1 total 1182:1186 a total 1180:1186 a total of 5105 proteins 1180:1203 Combining proteomics and modification specific proteomics we identified a total of 5105 proteins whereof 57% contained transmembrane domains or signal peptides. 24173317 0 6 theme neural 117:122 arg1 cells 129:133 human embryonic and neural stem cells 97:133 human embryonic and neural stem cells 97:133 Comprehensive quantitative comparison of the membrane proteome, phosphoproteome, and sialiome of human embryonic and neural stem cells. 24173317 11 7 theme protein 1956:1962 arg1 kinase-2 1964:1971 the calmodulin-dependent protein kinase-2 1931:1971 the calmodulin-dependent protein kinase-2 1931:1971 This motif is among other kinases recognized by the calmodulin-dependent protein kinase-2, emphasizing a possible importance of this kinase for this cell stage. 24173317 4 8 theme modified 668:675 arg1 acids 683:687 their modified amino acids 662:687 their modified amino acids 662:687 To obtain information about membrane-associated proteins and their modified amino acids potentially involved in changes of hESCs and NSCs as well as to investigate potential new markers for these two cell stages, we performed large-scale quantitative membrane-proteomic of hESCs and NSCs. 24173317 0 9 theme cells 129:133 arg1 comparison 27:36 Comprehensive quantitative comparison 0:36 Comprehensive quantitative comparison of the membrane proteome 0:61 Comprehensive quantitative comparison of the membrane proteome, phosphoproteome, and sialiome of human embryonic and neural stem cells. 24173317 0 9 theme cells 129:133 arg1 phosphoproteome 64:78 phosphoproteome 64:78 phosphoproteome 64:78 Comprehensive quantitative comparison of the membrane proteome, phosphoproteome, and sialiome of human embryonic and neural stem cells. 24173317 0 9 theme cells 129:133 arg1 sialiome 85:92 sialiome 85:92 sialiome 85:92 Comprehensive quantitative comparison of the membrane proteome, phosphoproteome, and sialiome of human embryonic and neural stem cells. 24173317 11 10 theme cell 2032:2035 arg1 stage 2037:2041 this cell stage 2027:2041 this cell stage 2027:2041 This motif is among other kinases recognized by the calmodulin-dependent protein kinase-2, emphasizing a possible importance of this kinase for this cell stage. 24173317 1 11 theme stem 201:204 arg1 NSCs 213:216 NSCs 213:216 NSCs 213:216 Human embryonic stem cells (hESCs) can differentiate into neural stem cells (NSCs), which can further be differentiated into neurons and glia cells. 24173317 1 11 theme stem 201:204 arg1 cells 206:210 neural stem cells 194:210 neural stem cells (NSCs) 194:217 Human embryonic stem cells (hESCs) can differentiate into neural stem cells (NSCs), which can further be differentiated into neurons and glia cells. 24173317 4 12 theme NSCs 734:737 arg1 changes 713:719 changes 713:719 changes of hESCs and NSCs 713:737 To obtain information about membrane-associated proteins and their modified amino acids potentially involved in changes of hESCs and NSCs as well as to investigate potential new markers for these two cell stages, we performed large-scale quantitative membrane-proteomic of hESCs and NSCs. 24173317 5 13 theme peptide 947:953 arg1 labeling 964:971 peptide dimethyl labeling 947:971 peptide dimethyl labeling 947:971 This approach employed membrane purification followed by peptide dimethyl labeling and peptide enrichment to study the membrane subproteome as well as changes in phosphorylation and sialylation between hESCs and NSCs. 24173317 7 14 theme % 1399:1399 arg1 confidence 1401:1410 ≥99% confidence 1396:1410 ≥99% confidence in site assignment 1396:1429 The enrichment strategy yielded a total of 10,087 phosphorylated peptides in which 78% of phosphopeptides were identified with ≥99% confidence in site assignment and 1810 unique formerly sialylated N-linked glycopeptides. 24173317 1 15 theme embryonic 142:150 arg1 hESCs 164:168 hESCs 164:168 hESCs 164:168 Human embryonic stem cells (hESCs) can differentiate into neural stem cells (NSCs), which can further be differentiated into neurons and glia cells. 24173317 1 15 theme embryonic 142:150 arg1 cells 157:161 Human embryonic stem cells 136:161 Human embryonic stem cells (hESCs) 136:169 Human embryonic stem cells (hESCs) can differentiate into neural stem cells (NSCs), which can further be differentiated into neurons and glia cells. 24173317 12 16 theme modifications 2121:2133 arg1 set 2095:2097 the most diverse set 2078:2097 the most diverse set of post-translational modifications reported for hESCs and NSCs 2078:2161 Collectively, this data represent the most diverse set of post-translational modifications reported for hESCs and NSCs. 24173317 12 16 theme modifications 2121:2133 arg1 modifications 2121:2133 post-translational modifications 2102:2133 post-translational modifications reported for hESCs and NSCs 2102:2161 Collectively, this data represent the most diverse set of post-translational modifications reported for hESCs and NSCs. 24173317 5 17 theme membrane 913:920 arg1 purification 922:933 membrane purification 913:933 membrane purification followed by peptide dimethyl labeling and peptide enrichment 913:994 This approach employed membrane purification followed by peptide dimethyl labeling and peptide enrichment to study the membrane subproteome as well as changes in phosphorylation and sialylation between hESCs and NSCs. 24173317 7 18 link N-linked 1467:1474 arg1 glycopeptides 1476:1488 1810 unique formerly sialylated N-linked glycopeptides 1435:1488 1810 unique formerly sialylated N-linked glycopeptides 1435:1488 The enrichment strategy yielded a total of 10,087 phosphorylated peptides in which 78% of phosphopeptides were identified with ≥99% confidence in site assignment and 1810 unique formerly sialylated N-linked glycopeptides. 24173317 4 19 theme hESCs 724:728 arg1 changes 713:719 changes 713:719 changes of hESCs and NSCs 713:737 To obtain information about membrane-associated proteins and their modified amino acids potentially involved in changes of hESCs and NSCs as well as to investigate potential new markers for these two cell stages, we performed large-scale quantitative membrane-proteomic of hESCs and NSCs. 24173317 7 20 theme enrichment 1273:1282 arg1 strategy 1284:1291 The enrichment strategy 1269:1291 The enrichment strategy 1269:1291 The enrichment strategy yielded a total of 10,087 phosphorylated peptides in which 78% of phosphopeptides were identified with ≥99% confidence in site assignment and 1810 unique formerly sialylated N-linked glycopeptides. 24173317 13 21 from understanding 2268:2280 arg1 process 2305:2311 the differentiation process 2285:2311 the differentiation process 2285:2311 This study revealed potential markers to distinguish NSCs from hESCs and will contribute to improve our understanding on the differentiation process. 24173317 2 22 contain have 308:311 arg1 cells 302:306 these cells 296:306 these cells 296:306 Therefore, these cells have huge potential as source for treatment of neurological diseases. 24173317 2 22 contain have 308:311 arg2 potential 318:326 huge potential 313:326 huge potential 313:326 Therefore, these cells have huge potential as source for treatment of neurological diseases. 24173317 10 23 theme sequence 1811:1818 arg1 R-X-XpS/T 1837:1845 R-X-XpS/T 1837:1845 R-X-XpS/T 1837:1845 A motif analysis of the altered phosphosites showed a sequence consensus motif (R-X-XpS/T) significantly up-regulated in NSC. 24173317 10 23 theme sequence 1811:1818 arg1 motif 1830:1834 a sequence consensus motif 1809:1834 a sequence consensus motif (R-X-XpS/T) significantly up-regulated in NSC 1809:1880 A motif analysis of the altered phosphosites showed a sequence consensus motif (R-X-XpS/T) significantly up-regulated in NSC. 24173317 0 24 theme embryonic 103:111 arg1 cells 129:133 human embryonic and neural stem cells 97:133 human embryonic and neural stem cells 97:133 Comprehensive quantitative comparison of the membrane proteome, phosphoproteome, and sialiome of human embryonic and neural stem cells. 24173317 7 25 theme ≥99 1396:1398 arg1 % 1399:1399 % 1399:1399 % 1399:1399 The enrichment strategy yielded a total of 10,087 phosphorylated peptides in which 78% of phosphopeptides were identified with ≥99% confidence in site assignment and 1810 unique formerly sialylated N-linked glycopeptides. 24173317 8 26 theme early 1604:1608 arg1 development 1631:1641 the early embryonic and neural development 1600:1641 the early embryonic and neural development 1600:1641 Several proteins were identified as significantly regulated in hESCs and NSC, including proteins involved in the early embryonic and neural development. 24173317 0 27 theme Comprehensive 0:12 arg1 comparison 27:36 Comprehensive quantitative comparison 0:36 Comprehensive quantitative comparison of the membrane proteome 0:61 Comprehensive quantitative comparison of the membrane proteome, phosphoproteome, and sialiome of human embryonic and neural stem cells. 24173317 0 27 theme Comprehensive 0:12 arg1 phosphoproteome 64:78 phosphoproteome 64:78 phosphoproteome 64:78 Comprehensive quantitative comparison of the membrane proteome, phosphoproteome, and sialiome of human embryonic and neural stem cells. 24173317 0 27 theme Comprehensive 0:12 arg1 sialiome 85:92 sialiome 85:92 sialiome 85:92 Comprehensive quantitative comparison of the membrane proteome, phosphoproteome, and sialiome of human embryonic and neural stem cells. 24173317 5 28 theme peptide 977:983 arg1 enrichment 985:994 peptide enrichment 977:994 peptide enrichment 977:994 This approach employed membrane purification followed by peptide dimethyl labeling and peptide enrichment to study the membrane subproteome as well as changes in phosphorylation and sialylation between hESCs and NSCs. 24173317 6 29 theme signal 1252:1257 arg1 peptides 1259:1266 signal peptides 1252:1266 signal peptides 1252:1266 Combining proteomics and modification specific proteomics we identified a total of 5105 proteins whereof 57% contained transmembrane domains or signal peptides. 24173317 4 30 theme potential 765:773 arg1 markers 779:785 potential new markers 765:785 potential new markers for these two cell stages 765:811 To obtain information about membrane-associated proteins and their modified amino acids potentially involved in changes of hESCs and NSCs as well as to investigate potential new markers for these two cell stages, we performed large-scale quantitative membrane-proteomic of hESCs and NSCs. 24173317 7 31 theme phosphopeptides 1359:1373 arg1 phosphopeptides 1359:1373 phosphopeptides 1359:1373 phosphopeptides 1359:1373 The enrichment strategy yielded a total of 10,087 phosphorylated peptides in which 78% of phosphopeptides were identified with ≥99% confidence in site assignment and 1810 unique formerly sialylated N-linked glycopeptides. 24173317 7 31 theme phosphopeptides 1359:1373 arg1 % 1354:1354 78% 1352:1354 78% of phosphopeptides 1352:1373 The enrichment strategy yielded a total of 10,087 phosphorylated peptides in which 78% of phosphopeptides were identified with ≥99% confidence in site assignment and 1810 unique formerly sialylated N-linked glycopeptides. 24173317 11 32 theme possible 1988:1995 arg1 importance 1997:2006 a possible importance 1986:2006 a possible importance of this kinase for this cell stage 1986:2041 This motif is among other kinases recognized by the calmodulin-dependent protein kinase-2, emphasizing a possible importance of this kinase for this cell stage. 24173317 2 33 theme diseases 368:375 arg1 treatment 342:350 treatment 342:350 treatment of neurological diseases 342:375 Therefore, these cells have huge potential as source for treatment of neurological diseases. 24173317 9 34 theme proteins 1667:1674 arg1 proteins 1667:1674 proteins 1667:1674 proteins 1667:1674 In the latter group of proteins, we could identify potential NSC markers as Crumbs 2 and several novel proteins. 24173317 9 34 theme proteins 1667:1674 arg1 group 1658:1662 the latter group 1647:1662 the latter group of proteins 1647:1674 In the latter group of proteins, we could identify potential NSC markers as Crumbs 2 and several novel proteins. 24173317 4 35 theme quantitative 839:850 arg1 membrane-proteomic 852:869 large-scale quantitative membrane-proteomic 827:869 large-scale quantitative membrane-proteomic of hESCs and NSCs 827:887 To obtain information about membrane-associated proteins and their modified amino acids potentially involved in changes of hESCs and NSCs as well as to investigate potential new markers for these two cell stages, we performed large-scale quantitative membrane-proteomic of hESCs and NSCs. 24173317 0 36 theme proteome 54:61 arg1 comparison 27:36 Comprehensive quantitative comparison 0:36 Comprehensive quantitative comparison of the membrane proteome 0:61 Comprehensive quantitative comparison of the membrane proteome, phosphoproteome, and sialiome of human embryonic and neural stem cells. 24173317 0 36 theme proteome 54:61 arg1 phosphoproteome 64:78 phosphoproteome 64:78 phosphoproteome 64:78 Comprehensive quantitative comparison of the membrane proteome, phosphoproteome, and sialiome of human embryonic and neural stem cells. 24173317 0 36 theme proteome 54:61 arg1 sialiome 85:92 sialiome 85:92 sialiome 85:92 Comprehensive quantitative comparison of the membrane proteome, phosphoproteome, and sialiome of human embryonic and neural stem cells. 24173317 8 37 theme Several 1491:1497 arg1 proteins 1499:1506 Several proteins 1491:1506 Several proteins 1491:1506 Several proteins were identified as significantly regulated in hESCs and NSC, including proteins involved in the early embryonic and neural development. 24173317 7 38 theme peptides 1334:1341 arg1 total 1303:1307 a total 1301:1307 a total of 10,087 phosphorylated peptides in which 78% of phosphopeptides were identified with ≥99% confidence in site assignment and 1810 unique formerly sialylated N-linked glycopeptides 1301:1488 The enrichment strategy yielded a total of 10,087 phosphorylated peptides in which 78% of phosphopeptides were identified with ≥99% confidence in site assignment and 1810 unique formerly sialylated N-linked glycopeptides. 24173317 6 39 contain contained 1217:1225 arg2 domains 1241:1247 transmembrane domains 1227:1247 transmembrane domains 1227:1247 Combining proteomics and modification specific proteomics we identified a total of 5105 proteins whereof 57% contained transmembrane domains or signal peptides. 24173317 6 39 contain contained 1217:1225 arg1 % 1215:1215 57% 1213:1215 57% 1213:1215 Combining proteomics and modification specific proteomics we identified a total of 5105 proteins whereof 57% contained transmembrane domains or signal peptides. 24173317 6 39 contain contained 1217:1225 arg2 peptides 1259:1266 signal peptides 1252:1266 signal peptides 1252:1266 Combining proteomics and modification specific proteomics we identified a total of 5105 proteins whereof 57% contained transmembrane domains or signal peptides. 24173317 2 40 theme neurological 355:366 arg1 diseases 368:375 neurological diseases 355:375 neurological diseases 355:375 Therefore, these cells have huge potential as source for treatment of neurological diseases. 24173317 10 41 theme phosphosites 1789:1800 arg1 analysis 1765:1772 A motif analysis 1757:1772 A motif analysis of the altered phosphosites 1757:1800 A motif analysis of the altered phosphosites showed a sequence consensus motif (R-X-XpS/T) significantly up-regulated in NSC. 24173317 9 42 theme NSC 1705:1707 arg1 markers 1709:1715 potential NSC markers 1695:1715 potential NSC markers 1695:1715 In the latter group of proteins, we could identify potential NSC markers as Crumbs 2 and several novel proteins. 24173317 9 42 theme NSC 1705:1707 arg1 proteins 1747:1754 several novel proteins 1733:1754 several novel proteins 1733:1754 In the latter group of proteins, we could identify potential NSC markers as Crumbs 2 and several novel proteins. 24173317 3 43 from important 416:424 arg1 recognition 452:462 recognition 452:462 recognition 452:462 Membrane-associated proteins are very important in cellular signaling and recognition, and their function and activity are frequently regulated by post-translational modifications such as phosphorylation and glycosylation. 24173317 3 43 from important 416:424 arg1 signaling 438:446 cellular signaling 429:446 cellular signaling 429:446 Membrane-associated proteins are very important in cellular signaling and recognition, and their function and activity are frequently regulated by post-translational modifications such as phosphorylation and glycosylation. 24173317 2 44 theme huge 313:316 arg1 potential 318:326 huge potential 313:326 huge potential 313:326 Therefore, these cells have huge potential as source for treatment of neurological diseases. 24173317 5 45 from subproteome 1018:1028 arg1 phosphorylation 1052:1066 phosphorylation 1052:1066 phosphorylation 1052:1066 This approach employed membrane purification followed by peptide dimethyl labeling and peptide enrichment to study the membrane subproteome as well as changes in phosphorylation and sialylation between hESCs and NSCs. 24173317 5 45 from subproteome 1018:1028 arg1 sialylation 1072:1082 sialylation 1072:1082 sialylation 1072:1082 This approach employed membrane purification followed by peptide dimethyl labeling and peptide enrichment to study the membrane subproteome as well as changes in phosphorylation and sialylation between hESCs and NSCs. 24173317 4 46 theme NSCs 884:887 arg1 membrane-proteomic 852:869 large-scale quantitative membrane-proteomic 827:869 large-scale quantitative membrane-proteomic of hESCs and NSCs 827:887 To obtain information about membrane-associated proteins and their modified amino acids potentially involved in changes of hESCs and NSCs as well as to investigate potential new markers for these two cell stages, we performed large-scale quantitative membrane-proteomic of hESCs and NSCs. 24173317 6 47 theme modification 1133:1144 arg1 proteomics 1155:1164 proteomics and modification specific proteomics 1118:1164 proteomics 1155:1164 Combining proteomics and modification specific proteomics we identified a total of 5105 proteins whereof 57% contained transmembrane domains or signal peptides. 24173317 10 48 theme consensus 1820:1828 arg1 R-X-XpS/T 1837:1845 R-X-XpS/T 1837:1845 R-X-XpS/T 1837:1845 A motif analysis of the altered phosphosites showed a sequence consensus motif (R-X-XpS/T) significantly up-regulated in NSC. 24173317 10 48 theme consensus 1820:1828 arg1 motif 1830:1834 a sequence consensus motif 1809:1834 a sequence consensus motif (R-X-XpS/T) significantly up-regulated in NSC 1809:1880 A motif analysis of the altered phosphosites showed a sequence consensus motif (R-X-XpS/T) significantly up-regulated in NSC. 24173317 7 49 dep N-linked 1467:1474 arg1 sialylated 1456:1465 sialylated 1456:1465 sialylated 1456:1465 The enrichment strategy yielded a total of 10,087 phosphorylated peptides in which 78% of phosphopeptides were identified with ≥99% confidence in site assignment and 1810 unique formerly sialylated N-linked glycopeptides. 24173317 5 50 from changes 1041:1047 arg1 phosphorylation 1052:1066 phosphorylation 1052:1066 phosphorylation 1052:1066 This approach employed membrane purification followed by peptide dimethyl labeling and peptide enrichment to study the membrane subproteome as well as changes in phosphorylation and sialylation between hESCs and NSCs. 24173317 5 50 from changes 1041:1047 arg1 sialylation 1072:1082 sialylation 1072:1082 sialylation 1072:1082 This approach employed membrane purification followed by peptide dimethyl labeling and peptide enrichment to study the membrane subproteome as well as changes in phosphorylation and sialylation between hESCs and NSCs. 24173317 9 51 theme several 1733:1739 arg1 markers 1709:1715 potential NSC markers 1695:1715 potential NSC markers 1695:1715 In the latter group of proteins, we could identify potential NSC markers as Crumbs 2 and several novel proteins. 24173317 9 51 theme several 1733:1739 arg1 proteins 1747:1754 several novel proteins 1733:1754 several novel proteins 1733:1754 In the latter group of proteins, we could identify potential NSC markers as Crumbs 2 and several novel proteins. 24173317 4 52 theme amino 677:681 arg1 acids 683:687 their modified amino acids 662:687 their modified amino acids 662:687 To obtain information about membrane-associated proteins and their modified amino acids potentially involved in changes of hESCs and NSCs as well as to investigate potential new markers for these two cell stages, we performed large-scale quantitative membrane-proteomic of hESCs and NSCs. 24173317 4 53 theme hESCs 874:878 arg1 membrane-proteomic 852:869 large-scale quantitative membrane-proteomic 827:869 large-scale quantitative membrane-proteomic of hESCs and NSCs 827:887 To obtain information about membrane-associated proteins and their modified amino acids potentially involved in changes of hESCs and NSCs as well as to investigate potential new markers for these two cell stages, we performed large-scale quantitative membrane-proteomic of hESCs and NSCs. 24173317 0 54 theme stem 124:127 arg1 cells 129:133 human embryonic and neural stem cells 97:133 human embryonic and neural stem cells 97:133 Comprehensive quantitative comparison of the membrane proteome, phosphoproteome, and sialiome of human embryonic and neural stem cells. 24173317 6 55 theme 5105 1191:1194 arg1 proteins 1196:1203 5105 proteins 1191:1203 5105 proteins 1191:1203 Combining proteomics and modification specific proteomics we identified a total of 5105 proteins whereof 57% contained transmembrane domains or signal peptides. 24173317 1 56 theme neural 194:199 arg1 NSCs 213:216 NSCs 213:216 NSCs 213:216 Human embryonic stem cells (hESCs) can differentiate into neural stem cells (NSCs), which can further be differentiated into neurons and glia cells. 24173317 1 56 theme neural 194:199 arg1 cells 206:210 neural stem cells 194:210 neural stem cells (NSCs) 194:217 Human embryonic stem cells (hESCs) can differentiate into neural stem cells (NSCs), which can further be differentiated into neurons and glia cells. 24173317 7 57 theme unique 1440:1445 arg1 glycopeptides 1476:1488 1810 unique formerly sialylated N-linked glycopeptides 1435:1488 1810 unique formerly sialylated N-linked glycopeptides 1435:1488 The enrichment strategy yielded a total of 10,087 phosphorylated peptides in which 78% of phosphopeptides were identified with ≥99% confidence in site assignment and 1810 unique formerly sialylated N-linked glycopeptides. 24173317 11 58 theme kinase 2016:2021 arg1 importance 1997:2006 a possible importance 1986:2006 a possible importance of this kinase for this cell stage 1986:2041 This motif is among other kinases recognized by the calmodulin-dependent protein kinase-2, emphasizing a possible importance of this kinase for this cell stage. 24173317 6 59 theme transmembrane 1227:1239 arg1 domains 1241:1247 transmembrane domains 1227:1247 transmembrane domains 1227:1247 Combining proteomics and modification specific proteomics we identified a total of 5105 proteins whereof 57% contained transmembrane domains or signal peptides. 24173317 4 60 theme cell 801:804 arg1 stages 806:811 these two cell stages 791:811 these two cell stages 791:811 To obtain information about membrane-associated proteins and their modified amino acids potentially involved in changes of hESCs and NSCs as well as to investigate potential new markers for these two cell stages, we performed large-scale quantitative membrane-proteomic of hESCs and NSCs. 24173317 5 61 theme dimethyl 955:962 arg1 labeling 964:971 peptide dimethyl labeling 947:971 peptide dimethyl labeling 947:971 This approach employed membrane purification followed by peptide dimethyl labeling and peptide enrichment to study the membrane subproteome as well as changes in phosphorylation and sialylation between hESCs and NSCs. 24173317 7 62 theme site 1415:1418 arg1 assignment 1420:1429 site assignment 1415:1429 site assignment 1415:1429 The enrichment strategy yielded a total of 10,087 phosphorylated peptides in which 78% of phosphopeptides were identified with ≥99% confidence in site assignment and 1810 unique formerly sialylated N-linked glycopeptides. 24173317 13 63 theme potential 2184:2192 arg1 markers 2194:2200 potential markers 2184:2200 potential markers 2184:2200 This study revealed potential markers to distinguish NSCs from hESCs and will contribute to improve our understanding on the differentiation process. 24173317 1 64 theme Human 136:140 arg1 hESCs 164:168 hESCs 164:168 hESCs 164:168 Human embryonic stem cells (hESCs) can differentiate into neural stem cells (NSCs), which can further be differentiated into neurons and glia cells. 24173317 1 64 theme Human 136:140 arg1 cells 157:161 Human embryonic stem cells 136:161 Human embryonic stem cells (hESCs) 136:169 Human embryonic stem cells (hESCs) can differentiate into neural stem cells (NSCs), which can further be differentiated into neurons and glia cells. 24173317 7 65 from glycopeptides 1476:1488 arg1 assignment 1420:1429 site assignment 1415:1429 site assignment 1415:1429 The enrichment strategy yielded a total of 10,087 phosphorylated peptides in which 78% of phosphopeptides were identified with ≥99% confidence in site assignment and 1810 unique formerly sialylated N-linked glycopeptides. 24173317 12 66 theme post-translational 2102:2119 arg1 modifications 2121:2133 post-translational modifications 2102:2133 post-translational modifications reported for hESCs and NSCs 2102:2161 Collectively, this data represent the most diverse set of post-translational modifications reported for hESCs and NSCs. 24173317 1 67 theme stem 152:155 arg1 hESCs 164:168 hESCs 164:168 hESCs 164:168 Human embryonic stem cells (hESCs) can differentiate into neural stem cells (NSCs), which can further be differentiated into neurons and glia cells. 24173317 1 67 theme stem 152:155 arg1 cells 157:161 Human embryonic stem cells 136:161 Human embryonic stem cells (hESCs) 136:169 Human embryonic stem cells (hESCs) can differentiate into neural stem cells (NSCs), which can further be differentiated into neurons and glia cells. 24173317 0 68 theme human 97:101 arg1 cells 129:133 human embryonic and neural stem cells 97:133 human embryonic and neural stem cells 97:133 Comprehensive quantitative comparison of the membrane proteome, phosphoproteome, and sialiome of human embryonic and neural stem cells. 24173317 4 69 theme new 775:777 arg1 markers 779:785 potential new markers 765:785 potential new markers for these two cell stages 765:811 To obtain information about membrane-associated proteins and their modified amino acids potentially involved in changes of hESCs and NSCs as well as to investigate potential new markers for these two cell stages, we performed large-scale quantitative membrane-proteomic of hESCs and NSCs. 24173317 5 70 theme membrane 1009:1016 arg1 subproteome 1018:1028 the membrane subproteome 1005:1028 the membrane subproteome as well as changes in phosphorylation and sialylation between hESCs and NSCs 1005:1105 This approach employed membrane purification followed by peptide dimethyl labeling and peptide enrichment to study the membrane subproteome as well as changes in phosphorylation and sialylation between hESCs and NSCs. 24173317 7 71 from confidence 1401:1410 arg1 assignment 1420:1429 site assignment 1415:1429 site assignment 1415:1429 The enrichment strategy yielded a total of 10,087 phosphorylated peptides in which 78% of phosphopeptides were identified with ≥99% confidence in site assignment and 1810 unique formerly sialylated N-linked glycopeptides. 24173317 8 72 theme embryonic 1610:1618 arg1 development 1631:1641 the early embryonic and neural development 1600:1641 the early embryonic and neural development 1600:1641 Several proteins were identified as significantly regulated in hESCs and NSC, including proteins involved in the early embryonic and neural development. 24173317 0 73 theme quantitative 14:25 arg1 comparison 27:36 Comprehensive quantitative comparison 0:36 Comprehensive quantitative comparison of the membrane proteome 0:61 Comprehensive quantitative comparison of the membrane proteome, phosphoproteome, and sialiome of human embryonic and neural stem cells. 24173317 0 73 theme quantitative 14:25 arg1 phosphoproteome 64:78 phosphoproteome 64:78 phosphoproteome 64:78 Comprehensive quantitative comparison of the membrane proteome, phosphoproteome, and sialiome of human embryonic and neural stem cells. 24173317 0 73 theme quantitative 14:25 arg1 sialiome 85:92 sialiome 85:92 sialiome 85:92 Comprehensive quantitative comparison of the membrane proteome, phosphoproteome, and sialiome of human embryonic and neural stem cells. 24173317 12 74 theme diverse 2087:2093 arg1 set 2095:2097 the most diverse set 2078:2097 the most diverse set of post-translational modifications reported for hESCs and NSCs 2078:2161 Collectively, this data represent the most diverse set of post-translational modifications reported for hESCs and NSCs. 24173317 12 74 theme diverse 2087:2093 arg1 modifications 2121:2133 post-translational modifications 2102:2133 post-translational modifications reported for hESCs and NSCs 2102:2161 Collectively, this data represent the most diverse set of post-translational modifications reported for hESCs and NSCs. 24173317 8 75 theme neural 1624:1629 arg1 development 1631:1641 the early embryonic and neural development 1600:1641 the early embryonic and neural development 1600:1641 Several proteins were identified as significantly regulated in hESCs and NSC, including proteins involved in the early embryonic and neural development. 24173317 9 76 theme latter 1651:1656 arg1 proteins 1667:1674 proteins 1667:1674 proteins 1667:1674 In the latter group of proteins, we could identify potential NSC markers as Crumbs 2 and several novel proteins. 24173317 9 76 theme latter 1651:1656 arg1 group 1658:1662 the latter group 1647:1662 the latter group of proteins 1647:1674 In the latter group of proteins, we could identify potential NSC markers as Crumbs 2 and several novel proteins. 24173317 11 77 theme calmodulin-dependent 1935:1954 arg1 kinase-2 1964:1971 the calmodulin-dependent protein kinase-2 1931:1971 the calmodulin-dependent protein kinase-2 1931:1971 This motif is among other kinases recognized by the calmodulin-dependent protein kinase-2, emphasizing a possible importance of this kinase for this cell stage. 24173317 0 78 theme membrane 45:52 arg1 proteome 54:61 the membrane proteome 41:61 the membrane proteome 41:61 Comprehensive quantitative comparison of the membrane proteome, phosphoproteome, and sialiome of human embryonic and neural stem cells. 24173317 3 79 theme Membrane-associated 378:396 arg1 proteins 398:405 Membrane-associated proteins 378:405 Membrane-associated proteins 378:405 Membrane-associated proteins are very important in cellular signaling and recognition, and their function and activity are frequently regulated by post-translational modifications such as phosphorylation and glycosylation. 24173317 13 80 from hESCs 2227:2231 arg1 NSCs 2217:2220 NSCs 2217:2220 NSCs from hESCs 2217:2231 This study revealed potential markers to distinguish NSCs from hESCs and will contribute to improve our understanding on the differentiation process. 24173317 3 81 theme cellular 429:436 arg1 signaling 438:446 cellular signaling 429:446 cellular signaling 429:446 Membrane-associated proteins are very important in cellular signaling and recognition, and their function and activity are frequently regulated by post-translational modifications such as phosphorylation and glycosylation. 24173317 1 82 theme glia 273:276 arg1 cells 278:282 glia cells 273:282 glia cells 273:282 Human embryonic stem cells (hESCs) can differentiate into neural stem cells (NSCs), which can further be differentiated into neurons and glia cells. 24173317 4 83 theme large-scale 827:837 arg1 membrane-proteomic 852:869 large-scale quantitative membrane-proteomic 827:869 large-scale quantitative membrane-proteomic of hESCs and NSCs 827:887 To obtain information about membrane-associated proteins and their modified amino acids potentially involved in changes of hESCs and NSCs as well as to investigate potential new markers for these two cell stages, we performed large-scale quantitative membrane-proteomic of hESCs and NSCs. 24173317 3 84 from signaling 438:446 arg1 important 416:424 important 416:424 important 416:424 Membrane-associated proteins are very important in cellular signaling and recognition, and their function and activity are frequently regulated by post-translational modifications such as phosphorylation and glycosylation. 24173317 10 85 theme motif 1759:1763 arg1 analysis 1765:1772 A motif analysis 1757:1772 A motif analysis of the altered phosphosites 1757:1800 A motif analysis of the altered phosphosites showed a sequence consensus motif (R-X-XpS/T) significantly up-regulated in NSC. 24173317 13 86 theme differentiation 2289:2303 arg1 process 2305:2311 the differentiation process 2285:2311 the differentiation process 2285:2311 This study revealed potential markers to distinguish NSCs from hESCs and will contribute to improve our understanding on the differentiation process. 24173317 7 87 theme phosphorylated 1319:1332 arg1 peptides 1334:1341 10,087 phosphorylated peptides 1312:1341 10,087 phosphorylated peptides in which 78% of phosphopeptides were identified with ≥99% confidence in site assignment and 1810 unique formerly sialylated N-linked glycopeptides 1312:1488 The enrichment strategy yielded a total of 10,087 phosphorylated peptides in which 78% of phosphopeptides were identified with ≥99% confidence in site assignment and 1810 unique formerly sialylated N-linked glycopeptides. 24173317 6 88 dep identified 1169:1178 arg1 Combining 1108:1116 Combining 1108:1116 Combining proteomics and modification specific proteomics 1108:1164 Combining proteomics and modification specific proteomics we identified a total of 5105 proteins whereof 57% contained transmembrane domains or signal peptides. 24173317 6 88 dep identified 1169:1178 arg1 contained 1217:1225 contained 1217:1225 contained transmembrane domains or signal peptides 1217:1266 Combining proteomics and modification specific proteomics we identified a total of 5105 proteins whereof 57% contained transmembrane domains or signal peptides. 24173317 11 89 theme other 1903:1907 arg1 kinases 1909:1915 other kinases 1903:1915 other kinases recognized by the calmodulin-dependent protein kinase-2 1903:1971 This motif is among other kinases recognized by the calmodulin-dependent protein kinase-2, emphasizing a possible importance of this kinase for this cell stage. 24173317 7 90 gly glycopeptides 1476:1488 arg2 glycopeptides 1476:1488 1810 unique formerly sialylated N-linked glycopeptides 1435:1488 1810 unique formerly sialylated N-linked glycopeptides 1435:1488 The enrichment strategy yielded a total of 10,087 phosphorylated peptides in which 78% of phosphopeptides were identified with ≥99% confidence in site assignment and 1810 unique formerly sialylated N-linked glycopeptides. 24173317 9 91 theme potential 1695:1703 arg1 markers 1709:1715 potential NSC markers 1695:1715 potential NSC markers 1695:1715 In the latter group of proteins, we could identify potential NSC markers as Crumbs 2 and several novel proteins. 24173317 9 91 theme potential 1695:1703 arg1 proteins 1747:1754 several novel proteins 1733:1754 several novel proteins 1733:1754 In the latter group of proteins, we could identify potential NSC markers as Crumbs 2 and several novel proteins. 24173317 6 92 theme proteomics 1118:1127 arg1 proteomics 1155:1164 proteomics and modification specific proteomics 1118:1164 proteomics 1155:1164 Combining proteomics and modification specific proteomics we identified a total of 5105 proteins whereof 57% contained transmembrane domains or signal peptides. 24173317 4 93 theme membrane-associated 629:647 arg1 proteins 649:656 membrane-associated proteins 629:656 membrane-associated proteins 629:656 To obtain information about membrane-associated proteins and their modified amino acids potentially involved in changes of hESCs and NSCs as well as to investigate potential new markers for these two cell stages, we performed large-scale quantitative membrane-proteomic of hESCs and NSCs. 24173317 10 94 theme altered 1781:1787 arg1 phosphosites 1789:1800 the altered phosphosites 1777:1800 the altered phosphosites 1777:1800 A motif analysis of the altered phosphosites showed a sequence consensus motif (R-X-XpS/T) significantly up-regulated in NSC. 24723968 2 0 theme functional 489:498 arg1 impacts 500:506 their functional impacts 483:506 their functional impacts on protein level 483:523 Despite the reported association of GalNAc-T1 gene mutations with human disease susceptibility, the comprehensive computational analysis of coding, noncoding and regulatory SNPs, and their functional impacts on protein level, still remains unknown. 24723968 2 0 theme functional 489:498 arg1 coding 440:445 coding 440:445 coding 440:445 Despite the reported association of GalNAc-T1 gene mutations with human disease susceptibility, the comprehensive computational analysis of coding, noncoding and regulatory SNPs, and their functional impacts on protein level, still remains unknown. 24723968 6 1 theme GalNAc-T1 1211:1219 arg1 enzyme 1221:1226 GalNAc-T1 enzyme 1211:1226 GalNAc-T1 enzyme 1211:1226 Using multiple computational approaches, we have systematically classified the functional mutations in regulatory and coding regions that can modify expression and function of GalNAc-T1 enzyme. 24723968 2 2 theme mutations 351:359 arg1 association 321:331 the reported association 308:331 the reported association of GalNAc-T1 gene mutations with human disease susceptibility 308:393 Despite the reported association of GalNAc-T1 gene mutations with human disease susceptibility, the comprehensive computational analysis of coding, noncoding and regulatory SNPs, and their functional impacts on protein level, still remains unknown. 24723968 7 3 theme therapeutic 1438:1448 arg1 elements 1450:1457 novel therapeutic elements 1432:1457 novel therapeutic elements for associated diseases 1432:1481 These genetic variants can further assist in better understanding the wide range of disease susceptibility associated with the mucin-based cell signalling and pathogenic binding, and may help to develop novel therapeutic elements for associated diseases. 24723968 0 4 theme consequences 72:83 arg1 analysis 30:37 First comprehensive in silico analysis 0:37 First comprehensive in silico analysis of the functional and structural consequences of SNPs in human GalNAc-T1 gene 0:115 First comprehensive in silico analysis of the functional and structural consequences of SNPs in human GalNAc-T1 gene. 24723968 6 5 theme computational 1050:1062 arg1 approaches 1064:1073 multiple computational approaches 1041:1073 multiple computational approaches 1041:1073 Using multiple computational approaches, we have systematically classified the functional mutations in regulatory and coding regions that can modify expression and function of GalNAc-T1 enzyme. 24723968 2 6 theme gene 346:349 arg1 mutations 351:359 GalNAc-T1 gene mutations 336:359 GalNAc-T1 gene mutations 336:359 Despite the reported association of GalNAc-T1 gene mutations with human disease susceptibility, the comprehensive computational analysis of coding, noncoding and regulatory SNPs, and their functional impacts on protein level, still remains unknown. 24723968 2 7 theme protein 511:517 arg1 level 519:523 protein level 511:523 protein level 511:523 Despite the reported association of GalNAc-T1 gene mutations with human disease susceptibility, the comprehensive computational analysis of coding, noncoding and regulatory SNPs, and their functional impacts on protein level, still remains unknown. 24723968 3 8 theme entire 638:643 arg1 SNPs 659:662 the entire listed coding SNPs 634:662 the entire listed coding SNPs of GalNAc-T1 gene 634:680 Therefore, sequence- and structure-based computational tools were employed to screen the entire listed coding SNPs of GalNAc-T1 gene in order to identify and characterize them. 24723968 5 9 theme regulatory 928:937 arg1 SNPs 939:942 2 regulatory SNPs 926:942 2 regulatory SNPs (rs72964406 and #x26; rs34304568) 926:976 Additionally, 2 regulatory SNPs (rs72964406 and #x26; rs34304568) were also identified in GalNAc-T1 by using FastSNP tool. 24723968 5 9 theme regulatory 928:937 arg1 # 960:960 # 960:960 # 960:960 Additionally, 2 regulatory SNPs (rs72964406 and #x26; rs34304568) were also identified in GalNAc-T1 by using FastSNP tool. 24723968 5 9 theme regulatory 928:937 arg1 rs72964406 945:954 rs72964406 945:954 rs72964406 945:954 Additionally, 2 regulatory SNPs (rs72964406 and #x26; rs34304568) were also identified in GalNAc-T1 by using FastSNP tool. 24723968 7 10 theme pathogenic 1388:1397 arg1 binding 1399:1405 pathogenic binding 1388:1405 pathogenic binding 1388:1405 These genetic variants can further assist in better understanding the wide range of disease susceptibility associated with the mucin-based cell signalling and pathogenic binding, and may help to develop novel therapeutic elements for associated diseases. 24723968 0 11 theme SNPs 88:91 arg1 consequences 72:83 the functional and structural consequences 42:83 the functional and structural consequences of SNPs in human GalNAc-T1 gene 42:115 First comprehensive in silico analysis of the functional and structural consequences of SNPs in human GalNAc-T1 gene. 24723968 2 12 from SNPs 473:476 arg1 level 519:523 protein level 511:523 protein level 511:523 Despite the reported association of GalNAc-T1 gene mutations with human disease susceptibility, the comprehensive computational analysis of coding, noncoding and regulatory SNPs, and their functional impacts on protein level, still remains unknown. 24723968 6 13 theme multiple 1041:1048 arg1 approaches 1064:1073 multiple computational approaches 1041:1073 multiple computational approaches 1041:1073 Using multiple computational approaches, we have systematically classified the functional mutations in regulatory and coding regions that can modify expression and function of GalNAc-T1 enzyme. 24723968 1 14 theme most 260:263 arg1 tissues 276:282 most biological tissues 260:282 most biological tissues 260:282 GalNAc-T1, a key candidate of GalNac-transferases genes family that is involved in mucin-type O-linked glycosylation pathway, is expressed in most biological tissues and cell types. 24723968 0 15 theme GalNAc-T1 102:110 arg1 gene 112:115 human GalNAc-T1 gene 96:115 human GalNAc-T1 gene 96:115 First comprehensive in silico analysis of the functional and structural consequences of SNPs in human GalNAc-T1 gene. 24723968 6 16 theme regulatory 1138:1147 arg1 regions 1160:1166 regulatory and coding regions 1138:1166 regions 1160:1166 Using multiple computational approaches, we have systematically classified the functional mutations in regulatory and coding regions that can modify expression and function of GalNAc-T1 enzyme. 24723968 7 17 theme disease 1313:1319 arg1 susceptibility 1321:1334 disease susceptibility 1313:1334 disease susceptibility associated with the mucin-based cell signalling and pathogenic binding 1313:1405 These genetic variants can further assist in better understanding the wide range of disease susceptibility associated with the mucin-based cell signalling and pathogenic binding, and may help to develop novel therapeutic elements for associated diseases. 24723968 1 18 theme GalNac-transferases 148:166 arg1 family 174:179 GalNac-transferases genes family 148:179 GalNac-transferases genes family that is involved in mucin-type O-linked glycosylation pathway 148:241 GalNAc-T1, a key candidate of GalNac-transferases genes family that is involved in mucin-type O-linked glycosylation pathway, is expressed in most biological tissues and cell types. 24723968 0 19 theme human 96:100 arg1 gene 112:115 human GalNAc-T1 gene 96:115 human GalNAc-T1 gene 96:115 First comprehensive in silico analysis of the functional and structural consequences of SNPs in human GalNAc-T1 gene. 24723968 4 20 theme potential 831:839 arg1 G258V 856:860 G258V 856:860 G258V 856:860 Our concordant in silico analysis by SIFT, PolyPhen-2, PANTHER-cSNP, and SNPeffect tools, identified the potential nsSNPs (S143P, G258V, and Y414D variants) from 18 nsSNPs of GalNAc-T1. 24723968 4 20 theme potential 831:839 arg1 S143P 849:853 S143P 849:853 S143P 849:853 Our concordant in silico analysis by SIFT, PolyPhen-2, PANTHER-cSNP, and SNPeffect tools, identified the potential nsSNPs (S143P, G258V, and Y414D variants) from 18 nsSNPs of GalNAc-T1. 24723968 4 20 theme potential 831:839 arg1 nsSNPs 841:846 the potential nsSNPs 827:846 the potential nsSNPs (S143P, G258V, and Y414D variants) 827:881 Our concordant in silico analysis by SIFT, PolyPhen-2, PANTHER-cSNP, and SNPeffect tools, identified the potential nsSNPs (S143P, G258V, and Y414D variants) from 18 nsSNPs of GalNAc-T1. 24723968 2 21 theme noncoding 448:456 arg1 SNPs 473:476 noncoding and regulatory SNPs 448:476 SNPs 473:476 Despite the reported association of GalNAc-T1 gene mutations with human disease susceptibility, the comprehensive computational analysis of coding, noncoding and regulatory SNPs, and their functional impacts on protein level, still remains unknown. 24723968 2 21 theme noncoding 448:456 arg1 coding 440:445 coding 440:445 coding 440:445 Despite the reported association of GalNAc-T1 gene mutations with human disease susceptibility, the comprehensive computational analysis of coding, noncoding and regulatory SNPs, and their functional impacts on protein level, still remains unknown. 24723968 1 22 theme genes 168:172 arg1 family 174:179 GalNac-transferases genes family 148:179 GalNac-transferases genes family that is involved in mucin-type O-linked glycosylation pathway 148:241 GalNAc-T1, a key candidate of GalNac-transferases genes family that is involved in mucin-type O-linked glycosylation pathway, is expressed in most biological tissues and cell types. 24723968 0 23 theme comprehensive 6:18 arg1 analysis 30:37 First comprehensive in silico analysis 0:37 First comprehensive in silico analysis of the functional and structural consequences of SNPs in human GalNAc-T1 gene 0:115 First comprehensive in silico analysis of the functional and structural consequences of SNPs in human GalNAc-T1 gene. 24723968 7 24 theme novel 1432:1436 arg1 elements 1450:1457 novel therapeutic elements 1432:1457 novel therapeutic elements for associated diseases 1432:1481 These genetic variants can further assist in better understanding the wide range of disease susceptibility associated with the mucin-based cell signalling and pathogenic binding, and may help to develop novel therapeutic elements for associated diseases. 24723968 6 25 theme enzyme 1221:1226 arg1 function 1199:1206 function 1199:1206 function 1199:1206 Using multiple computational approaches, we have systematically classified the functional mutations in regulatory and coding regions that can modify expression and function of GalNAc-T1 enzyme. 24723968 6 25 theme enzyme 1221:1226 arg1 expression 1184:1193 expression 1184:1193 expression 1184:1193 Using multiple computational approaches, we have systematically classified the functional mutations in regulatory and coding regions that can modify expression and function of GalNAc-T1 enzyme. 24723968 1 26 theme family 174:179 arg1 GalNAc-T1 118:126 GalNAc-T1 118:126 GalNAc-T1 118:126 GalNAc-T1, a key candidate of GalNac-transferases genes family that is involved in mucin-type O-linked glycosylation pathway, is expressed in most biological tissues and cell types. 24723968 1 26 theme family 174:179 arg1 candidate 135:143 a key candidate 129:143 a key candidate of GalNac-transferases genes family that is involved in mucin-type O-linked glycosylation pathway 129:241 GalNAc-T1, a key candidate of GalNac-transferases genes family that is involved in mucin-type O-linked glycosylation pathway, is expressed in most biological tissues and cell types. 24723968 0 27 theme First 0:4 arg1 analysis 30:37 First comprehensive in silico analysis 0:37 First comprehensive in silico analysis of the functional and structural consequences of SNPs in human GalNAc-T1 gene 0:115 First comprehensive in silico analysis of the functional and structural consequences of SNPs in human GalNAc-T1 gene. 24723968 1 28 theme biological 265:274 arg1 tissues 276:282 most biological tissues 260:282 most biological tissues 260:282 GalNAc-T1, a key candidate of GalNac-transferases genes family that is involved in mucin-type O-linked glycosylation pathway, is expressed in most biological tissues and cell types. 24723968 3 29 theme gene 677:680 arg1 SNPs 659:662 the entire listed coding SNPs 634:662 the entire listed coding SNPs of GalNAc-T1 gene 634:680 Therefore, sequence- and structure-based computational tools were employed to screen the entire listed coding SNPs of GalNAc-T1 gene in order to identify and characterize them. 24723968 1 30 link O-linked 212:219 arg1 glycosylation 221:233 mucin-type O-linked glycosylation 201:233 mucin-type O-linked glycosylation pathway 201:241 GalNAc-T1, a key candidate of GalNac-transferases genes family that is involved in mucin-type O-linked glycosylation pathway, is expressed in most biological tissues and cell types. 24723968 3 31 theme structure-based 574:588 arg1 tools 604:608 structure-based computational tools 574:608 structure-based computational tools 574:608 Therefore, sequence- and structure-based computational tools were employed to screen the entire listed coding SNPs of GalNAc-T1 gene in order to identify and characterize them. 24723968 2 32 theme disease 372:378 arg1 susceptibility 380:393 human disease susceptibility 366:393 human disease susceptibility 366:393 Despite the reported association of GalNAc-T1 gene mutations with human disease susceptibility, the comprehensive computational analysis of coding, noncoding and regulatory SNPs, and their functional impacts on protein level, still remains unknown. 24723968 4 33 dep nsSNPs 841:846 arg1 G258V 856:860 G258V 856:860 G258V 856:860 Our concordant in silico analysis by SIFT, PolyPhen-2, PANTHER-cSNP, and SNPeffect tools, identified the potential nsSNPs (S143P, G258V, and Y414D variants) from 18 nsSNPs of GalNAc-T1. 24723968 4 33 dep nsSNPs 841:846 arg1 S143P 849:853 S143P 849:853 S143P 849:853 Our concordant in silico analysis by SIFT, PolyPhen-2, PANTHER-cSNP, and SNPeffect tools, identified the potential nsSNPs (S143P, G258V, and Y414D variants) from 18 nsSNPs of GalNAc-T1. 24723968 4 33 dep nsSNPs 841:846 arg1 variants 873:880 Y414D variants 867:880 Y414D variants 867:880 Our concordant in silico analysis by SIFT, PolyPhen-2, PANTHER-cSNP, and SNPeffect tools, identified the potential nsSNPs (S143P, G258V, and Y414D variants) from 18 nsSNPs of GalNAc-T1. 24723968 4 33 dep nsSNPs 841:846 arg1 nsSNPs 841:846 the potential nsSNPs 827:846 the potential nsSNPs (S143P, G258V, and Y414D variants) 827:881 Our concordant in silico analysis by SIFT, PolyPhen-2, PANTHER-cSNP, and SNPeffect tools, identified the potential nsSNPs (S143P, G258V, and Y414D variants) from 18 nsSNPs of GalNAc-T1. 24723968 4 34 theme in 741:742 arg1 analysis 751:758 Our concordant in silico analysis 726:758 Our concordant in silico analysis by SIFT 726:766 Our concordant in silico analysis by SIFT, PolyPhen-2, PANTHER-cSNP, and SNPeffect tools, identified the potential nsSNPs (S143P, G258V, and Y414D variants) from 18 nsSNPs of GalNAc-T1. 24723968 2 35 theme comprehensive 400:412 arg1 analysis 428:435 the comprehensive computational analysis 396:435 the comprehensive computational analysis of coding, noncoding and regulatory SNPs, and their functional impacts on protein level, 396:524 Despite the reported association of GalNAc-T1 gene mutations with human disease susceptibility, the comprehensive computational analysis of coding, noncoding and regulatory SNPs, and their functional impacts on protein level, still remains unknown. 24723968 0 36 theme in 20:21 arg1 analysis 30:37 First comprehensive in silico analysis 0:37 First comprehensive in silico analysis of the functional and structural consequences of SNPs in human GalNAc-T1 gene 0:115 First comprehensive in silico analysis of the functional and structural consequences of SNPs in human GalNAc-T1 gene. 24723968 6 37 theme coding 1153:1158 arg1 regions 1160:1166 regulatory and coding regions 1138:1166 regions 1160:1166 Using multiple computational approaches, we have systematically classified the functional mutations in regulatory and coding regions that can modify expression and function of GalNAc-T1 enzyme. 24723968 2 38 with association 321:331 arg1 susceptibility 380:393 human disease susceptibility 366:393 human disease susceptibility 366:393 Despite the reported association of GalNAc-T1 gene mutations with human disease susceptibility, the comprehensive computational analysis of coding, noncoding and regulatory SNPs, and their functional impacts on protein level, still remains unknown. 24723968 4 39 dep in 741:742 arg1 silico 744:749 silico 744:749 silico 744:749 Our concordant in silico analysis by SIFT, PolyPhen-2, PANTHER-cSNP, and SNPeffect tools, identified the potential nsSNPs (S143P, G258V, and Y414D variants) from 18 nsSNPs of GalNAc-T1. 24723968 6 40 from mutations 1125:1133 arg1 regions 1160:1166 regulatory and coding regions 1138:1166 regions 1160:1166 Using multiple computational approaches, we have systematically classified the functional mutations in regulatory and coding regions that can modify expression and function of GalNAc-T1 enzyme. 24723968 6 41 theme functional 1114:1123 arg1 mutations 1125:1133 the functional mutations 1110:1133 the functional mutations in regulatory and coding regions that can modify expression and function of GalNAc-T1 enzyme 1110:1226 Using multiple computational approaches, we have systematically classified the functional mutations in regulatory and coding regions that can modify expression and function of GalNAc-T1 enzyme. 24723968 1 42 theme cell 288:291 arg1 types 293:297 cell types 288:297 cell types 288:297 GalNAc-T1, a key candidate of GalNac-transferases genes family that is involved in mucin-type O-linked glycosylation pathway, is expressed in most biological tissues and cell types. 24723968 4 43 theme GalNAc-T1 901:909 arg1 nsSNPs 891:896 18 nsSNPs 888:896 18 nsSNPs of GalNAc-T1 888:909 Our concordant in silico analysis by SIFT, PolyPhen-2, PANTHER-cSNP, and SNPeffect tools, identified the potential nsSNPs (S143P, G258V, and Y414D variants) from 18 nsSNPs of GalNAc-T1. 24723968 0 44 from consequences 72:83 arg1 gene 112:115 human GalNAc-T1 gene 96:115 human GalNAc-T1 gene 96:115 First comprehensive in silico analysis of the functional and structural consequences of SNPs in human GalNAc-T1 gene. 24723968 7 45 theme cell 1368:1371 arg1 signalling 1373:1382 the mucin-based cell signalling 1352:1382 the mucin-based cell signalling 1352:1382 These genetic variants can further assist in better understanding the wide range of disease susceptibility associated with the mucin-based cell signalling and pathogenic binding, and may help to develop novel therapeutic elements for associated diseases. 24723968 7 46 theme wide 1299:1302 arg1 range 1304:1308 the wide range 1295:1308 the wide range of disease susceptibility associated with the mucin-based cell signalling and pathogenic binding 1295:1405 These genetic variants can further assist in better understanding the wide range of disease susceptibility associated with the mucin-based cell signalling and pathogenic binding, and may help to develop novel therapeutic elements for associated diseases. 24723968 2 47 theme computational 414:426 arg1 analysis 428:435 the comprehensive computational analysis 396:435 the comprehensive computational analysis of coding, noncoding and regulatory SNPs, and their functional impacts on protein level, 396:524 Despite the reported association of GalNAc-T1 gene mutations with human disease susceptibility, the comprehensive computational analysis of coding, noncoding and regulatory SNPs, and their functional impacts on protein level, still remains unknown. 24723968 3 48 theme listed 645:650 arg1 SNPs 659:662 the entire listed coding SNPs 634:662 the entire listed coding SNPs of GalNAc-T1 gene 634:680 Therefore, sequence- and structure-based computational tools were employed to screen the entire listed coding SNPs of GalNAc-T1 gene in order to identify and characterize them. 24723968 1 49 theme mucin-type 201:210 arg1 glycosylation 221:233 mucin-type O-linked glycosylation 201:233 mucin-type O-linked glycosylation pathway 201:241 GalNAc-T1, a key candidate of GalNac-transferases genes family that is involved in mucin-type O-linked glycosylation pathway, is expressed in most biological tissues and cell types. 24723968 0 50 theme functional 46:55 arg1 consequences 72:83 the functional and structural consequences 42:83 the functional and structural consequences of SNPs in human GalNAc-T1 gene 42:115 First comprehensive in silico analysis of the functional and structural consequences of SNPs in human GalNAc-T1 gene. 24723968 2 51 from impacts 500:506 arg1 level 519:523 protein level 511:523 protein level 511:523 Despite the reported association of GalNAc-T1 gene mutations with human disease susceptibility, the comprehensive computational analysis of coding, noncoding and regulatory SNPs, and their functional impacts on protein level, still remains unknown. 24723968 3 52 theme computational 590:602 arg1 tools 604:608 structure-based computational tools 574:608 structure-based computational tools 574:608 Therefore, sequence- and structure-based computational tools were employed to screen the entire listed coding SNPs of GalNAc-T1 gene in order to identify and characterize them. 24723968 2 53 theme GalNAc-T1 336:344 arg1 mutations 351:359 GalNAc-T1 gene mutations 336:359 GalNAc-T1 gene mutations 336:359 Despite the reported association of GalNAc-T1 gene mutations with human disease susceptibility, the comprehensive computational analysis of coding, noncoding and regulatory SNPs, and their functional impacts on protein level, still remains unknown. 24723968 2 54 theme regulatory 462:471 arg1 SNPs 473:476 noncoding and regulatory SNPs 448:476 SNPs 473:476 Despite the reported association of GalNAc-T1 gene mutations with human disease susceptibility, the comprehensive computational analysis of coding, noncoding and regulatory SNPs, and their functional impacts on protein level, still remains unknown. 24723968 2 54 theme regulatory 462:471 arg1 coding 440:445 coding 440:445 coding 440:445 Despite the reported association of GalNAc-T1 gene mutations with human disease susceptibility, the comprehensive computational analysis of coding, noncoding and regulatory SNPs, and their functional impacts on protein level, still remains unknown. 24723968 4 55 theme Y414D 867:871 arg1 variants 873:880 Y414D variants 867:880 Y414D variants 867:880 Our concordant in silico analysis by SIFT, PolyPhen-2, PANTHER-cSNP, and SNPeffect tools, identified the potential nsSNPs (S143P, G258V, and Y414D variants) from 18 nsSNPs of GalNAc-T1. 24723968 3 56 theme coding 652:657 arg1 SNPs 659:662 the entire listed coding SNPs 634:662 the entire listed coding SNPs of GalNAc-T1 gene 634:680 Therefore, sequence- and structure-based computational tools were employed to screen the entire listed coding SNPs of GalNAc-T1 gene in order to identify and characterize them. 24723968 7 57 theme mucin-based 1356:1366 arg1 signalling 1373:1382 the mucin-based cell signalling 1352:1382 the mucin-based cell signalling 1352:1382 These genetic variants can further assist in better understanding the wide range of disease susceptibility associated with the mucin-based cell signalling and pathogenic binding, and may help to develop novel therapeutic elements for associated diseases. 24723968 7 58 theme associated 1463:1472 arg1 diseases 1474:1481 associated diseases 1463:1481 associated diseases 1463:1481 These genetic variants can further assist in better understanding the wide range of disease susceptibility associated with the mucin-based cell signalling and pathogenic binding, and may help to develop novel therapeutic elements for associated diseases. 24723968 7 59 theme susceptibility 1321:1334 arg1 range 1304:1308 the wide range 1295:1308 the wide range of disease susceptibility associated with the mucin-based cell signalling and pathogenic binding 1295:1405 These genetic variants can further assist in better understanding the wide range of disease susceptibility associated with the mucin-based cell signalling and pathogenic binding, and may help to develop novel therapeutic elements for associated diseases. 24723968 4 60 theme concordant 730:739 arg1 analysis 751:758 Our concordant in silico analysis 726:758 Our concordant in silico analysis by SIFT 726:766 Our concordant in silico analysis by SIFT, PolyPhen-2, PANTHER-cSNP, and SNPeffect tools, identified the potential nsSNPs (S143P, G258V, and Y414D variants) from 18 nsSNPs of GalNAc-T1. 24723968 1 61 theme O-linked 212:219 arg1 glycosylation 221:233 mucin-type O-linked glycosylation 201:233 mucin-type O-linked glycosylation pathway 201:241 GalNAc-T1, a key candidate of GalNac-transferases genes family that is involved in mucin-type O-linked glycosylation pathway, is expressed in most biological tissues and cell types. 24723968 3 62 theme GalNAc-T1 667:675 arg1 gene 677:680 GalNAc-T1 gene 667:680 GalNAc-T1 gene 667:680 Therefore, sequence- and structure-based computational tools were employed to screen the entire listed coding SNPs of GalNAc-T1 gene in order to identify and characterize them. 24723968 0 63 dep in 20:21 arg1 silico 23:28 silico 23:28 silico 23:28 First comprehensive in silico analysis of the functional and structural consequences of SNPs in human GalNAc-T1 gene. 24723968 5 64 theme FastSNP 1021:1027 arg1 tool 1029:1032 FastSNP tool 1021:1032 FastSNP tool 1021:1032 Additionally, 2 regulatory SNPs (rs72964406 and #x26; rs34304568) were also identified in GalNAc-T1 by using FastSNP tool. 24723968 2 65 theme reported 312:319 arg1 association 321:331 the reported association 308:331 the reported association of GalNAc-T1 gene mutations with human disease susceptibility 308:393 Despite the reported association of GalNAc-T1 gene mutations with human disease susceptibility, the comprehensive computational analysis of coding, noncoding and regulatory SNPs, and their functional impacts on protein level, still remains unknown. 24723968 1 66 theme glycosylation 221:233 arg1 pathway 235:241 mucin-type O-linked glycosylation pathway 201:241 mucin-type O-linked glycosylation pathway 201:241 GalNAc-T1, a key candidate of GalNac-transferases genes family that is involved in mucin-type O-linked glycosylation pathway, is expressed in most biological tissues and cell types. 24723968 0 67 theme structural 61:70 arg1 consequences 72:83 the functional and structural consequences 42:83 the functional and structural consequences of SNPs in human GalNAc-T1 gene 42:115 First comprehensive in silico analysis of the functional and structural consequences of SNPs in human GalNAc-T1 gene. 24723968 0 68 from SNPs 88:91 arg1 gene 112:115 human GalNAc-T1 gene 96:115 human GalNAc-T1 gene 96:115 First comprehensive in silico analysis of the functional and structural consequences of SNPs in human GalNAc-T1 gene. 24723968 4 69 theme SNPeffect 799:807 arg1 tools 809:813 SNPeffect tools 799:813 SNPeffect tools 799:813 Our concordant in silico analysis by SIFT, PolyPhen-2, PANTHER-cSNP, and SNPeffect tools, identified the potential nsSNPs (S143P, G258V, and Y414D variants) from 18 nsSNPs of GalNAc-T1. 24723968 2 70 theme human 366:370 arg1 susceptibility 380:393 human disease susceptibility 366:393 human disease susceptibility 366:393 Despite the reported association of GalNAc-T1 gene mutations with human disease susceptibility, the comprehensive computational analysis of coding, noncoding and regulatory SNPs, and their functional impacts on protein level, still remains unknown. 24723968 2 71 theme coding 440:445 arg1 analysis 428:435 the comprehensive computational analysis 396:435 the comprehensive computational analysis of coding, noncoding and regulatory SNPs, and their functional impacts on protein level, 396:524 Despite the reported association of GalNAc-T1 gene mutations with human disease susceptibility, the comprehensive computational analysis of coding, noncoding and regulatory SNPs, and their functional impacts on protein level, still remains unknown. 24723968 7 72 theme genetic 1235:1241 arg1 variants 1243:1250 These genetic variants 1229:1250 These genetic variants 1229:1250 These genetic variants can further assist in better understanding the wide range of disease susceptibility associated with the mucin-based cell signalling and pathogenic binding, and may help to develop novel therapeutic elements for associated diseases. 24723968 1 73 theme key 131:133 arg1 GalNAc-T1 118:126 GalNAc-T1 118:126 GalNAc-T1 118:126 GalNAc-T1, a key candidate of GalNac-transferases genes family that is involved in mucin-type O-linked glycosylation pathway, is expressed in most biological tissues and cell types. 24723968 1 73 theme key 131:133 arg1 candidate 135:143 a key candidate 129:143 a key candidate of GalNac-transferases genes family that is involved in mucin-type O-linked glycosylation pathway 129:241 GalNAc-T1, a key candidate of GalNac-transferases genes family that is involved in mucin-type O-linked glycosylation pathway, is expressed in most biological tissues and cell types. 24723968 0 74 from gene 112:115 arg1 consequences 72:83 the functional and structural consequences 42:83 the functional and structural consequences of SNPs in human GalNAc-T1 gene 42:115 First comprehensive in silico analysis of the functional and structural consequences of SNPs in human GalNAc-T1 gene. 24265318 4 0 theme Env 564:566 arg1 signatures 568:577 specific Env signatures 555:577 specific Env signatures 555:577 This raises the question of whether primary Envs derived from HIV-infected patients are capable of inducing bystander apoptosis and whether specific Env signatures are associated with this phenomenon. 24265318 7 1 theme apoptosis-inducing 1110:1127 arg1 potential 1129:1137 their bystander apoptosis-inducing potential 1094:1137 their bystander apoptosis-inducing potential 1094:1137 Our studies show that primary Envs vary considerably in their bystander apoptosis-inducing potential, a phenomenon that correlates inversely with putative N-linked glycosylation sites and positively with virion infectivity. 24265318 7 1 theme apoptosis-inducing 1110:1127 arg1 phenomenon 1142:1151 a phenomenon 1140:1151 a phenomenon that correlates inversely with putative N-linked glycosylation sites and positively with virion infectivity 1140:1259 Our studies show that primary Envs vary considerably in their bystander apoptosis-inducing potential, a phenomenon that correlates inversely with putative N-linked glycosylation sites and positively with virion infectivity. 24265318 6 2 theme bystander 768:776 arg1 apoptosis 778:786 bystander apoptosis 768:786 bystander apoptosis 768:786 We tested 38 different Envs for bystander apoptosis, virion infectivity, neutralizing antibody sensitivity, and putative N-linked glycosylation sites along with a comprehensive sequence analysis to determine if specific sequence signatures within the viral Env are associated with bystander apoptosis. 24265318 2 3 theme contributing 259:270 arg1 apoptosis 235:243 bystander apoptosis 225:243 bystander apoptosis that may be a contributing factor in CD4(+) T cell loss 225:299 Several lines of evidence support the role of HIV-1 Env in inducing bystander apoptosis that may be a contributing factor in CD4(+) T cell loss. 24265318 2 3 theme contributing 259:270 arg1 factor 272:277 a contributing factor 257:277 a contributing factor 257:277 Several lines of evidence support the role of HIV-1 Env in inducing bystander apoptosis that may be a contributing factor in CD4(+) T cell loss. 24265318 6 4 theme glycosylation 866:878 arg1 sites 880:884 putative N-linked glycosylation sites 848:884 putative N-linked glycosylation sites 848:884 We tested 38 different Envs for bystander apoptosis, virion infectivity, neutralizing antibody sensitivity, and putative N-linked glycosylation sites along with a comprehensive sequence analysis to determine if specific sequence signatures within the viral Env are associated with bystander apoptosis. 24265318 7 5 theme N-linked 1193:1200 arg1 sites 1216:1220 putative N-linked glycosylation sites 1184:1220 putative N-linked glycosylation sites 1184:1220 Our studies show that primary Envs vary considerably in their bystander apoptosis-inducing potential, a phenomenon that correlates inversely with putative N-linked glycosylation sites and positively with virion infectivity. 24265318 6 6 theme putative 848:855 arg1 sites 880:884 putative N-linked glycosylation sites 848:884 putative N-linked glycosylation sites 848:884 We tested 38 different Envs for bystander apoptosis, virion infectivity, neutralizing antibody sensitivity, and putative N-linked glycosylation sites along with a comprehensive sequence analysis to determine if specific sequence signatures within the viral Env are associated with bystander apoptosis. 24265318 9 7 theme specific 1493:1500 arg1 role 1502:1505 A specific role 1491:1505 A specific role of these residues 1491:1523 A specific role of these residues was also confirmed experimentally. 24265318 6 8 theme sequence 956:963 arg1 signatures 965:974 specific sequence signatures 947:974 specific sequence signatures within the viral Env 947:995 We tested 38 different Envs for bystander apoptosis, virion infectivity, neutralizing antibody sensitivity, and putative N-linked glycosylation sites along with a comprehensive sequence analysis to determine if specific sequence signatures within the viral Env are associated with bystander apoptosis. 24265318 8 9 theme phylogenetic 1280:1291 arg1 analysis 1293:1300 a novel phylogenetic analysis 1272:1300 a novel phylogenetic analysis that avoids subtype bias coupled with structural considerations 1272:1364 By use of a novel phylogenetic analysis that avoids subtype bias coupled with structural considerations, we found specific residues like Arg-476 and Asn-425 that were associated with differences in bystander apoptosis induction. 24265318 10 10 theme R5 1627:1628 arg1 Envs 1630:1633 primary R5 Envs 1619:1633 primary R5 Envs 1619:1633 These data demonstrate for the first time the potential of primary R5 Envs to mediate bystander apoptosis in CD4(+) T cells. 24265318 5 11 theme apoptosis 680:688 arg1 activity 699:706 the bystander apoptosis inducing activity 666:706 the bystander apoptosis inducing activity of a panel of primary Envs 666:733 We developed a high throughput assay to determine the bystander apoptosis inducing activity of a panel of primary Envs. 24265318 9 12 theme residues 1516:1523 arg1 role 1502:1505 A specific role 1491:1505 A specific role of these residues 1491:1523 A specific role of these residues was also confirmed experimentally. 24265318 8 13 theme subtype 1314:1320 arg1 bias 1322:1325 subtype bias 1314:1325 subtype bias coupled with structural considerations 1314:1364 By use of a novel phylogenetic analysis that avoids subtype bias coupled with structural considerations, we found specific residues like Arg-476 and Asn-425 that were associated with differences in bystander apoptosis induction. 24265318 10 14 theme bystander 1646:1654 arg1 apoptosis 1656:1664 bystander apoptosis 1646:1664 bystander apoptosis in CD4(+) T cells 1646:1682 These data demonstrate for the first time the potential of primary R5 Envs to mediate bystander apoptosis in CD4(+) T cells. 24265318 2 15 theme HIV-1 203:207 arg1 Env 209:211 HIV-1 Env 203:211 HIV-1 Env 203:211 Several lines of evidence support the role of HIV-1 Env in inducing bystander apoptosis that may be a contributing factor in CD4(+) T cell loss. 24265318 7 16 theme bystander 1100:1108 arg1 potential 1129:1137 their bystander apoptosis-inducing potential 1094:1137 their bystander apoptosis-inducing potential 1094:1137 Our studies show that primary Envs vary considerably in their bystander apoptosis-inducing potential, a phenomenon that correlates inversely with putative N-linked glycosylation sites and positively with virion infectivity. 24265318 7 16 theme bystander 1100:1108 arg1 phenomenon 1142:1151 a phenomenon 1140:1151 a phenomenon that correlates inversely with putative N-linked glycosylation sites and positively with virion infectivity 1140:1259 Our studies show that primary Envs vary considerably in their bystander apoptosis-inducing potential, a phenomenon that correlates inversely with putative N-linked glycosylation sites and positively with virion infectivity. 24265318 6 17 theme sequence 913:920 arg1 analysis 922:929 a comprehensive sequence analysis 897:929 a comprehensive sequence analysis to determine if specific sequence signatures within the viral Env are associated with bystander apoptosis 897:1035 We tested 38 different Envs for bystander apoptosis, virion infectivity, neutralizing antibody sensitivity, and putative N-linked glycosylation sites along with a comprehensive sequence analysis to determine if specific sequence signatures within the viral Env are associated with bystander apoptosis. 24265318 2 18 from factor 272:277 arg1 loss 296:299 CD4(+) T cell loss 282:299 CD4(+) T cell loss 282:299 Several lines of evidence support the role of HIV-1 Env in inducing bystander apoptosis that may be a contributing factor in CD4(+) T cell loss. 24265318 8 19 theme structural 1340:1349 arg1 considerations 1351:1364 structural considerations 1340:1364 structural considerations 1340:1364 By use of a novel phylogenetic analysis that avoids subtype bias coupled with structural considerations, we found specific residues like Arg-476 and Asn-425 that were associated with differences in bystander apoptosis induction. 24265318 5 20 theme Envs 730:733 arg1 panel 713:717 a panel 711:717 a panel of primary Envs 711:733 We developed a high throughput assay to determine the bystander apoptosis inducing activity of a panel of primary Envs. 24265318 7 21 link N-linked 1193:1200 arg1 sites 1216:1220 putative N-linked glycosylation sites 1184:1220 putative N-linked glycosylation sites 1184:1220 Our studies show that primary Envs vary considerably in their bystander apoptosis-inducing potential, a phenomenon that correlates inversely with putative N-linked glycosylation sites and positively with virion infectivity. 24265318 1 22 theme viral 137:141 arg1 pathogenesis 143:154 viral pathogenesis 137:154 viral pathogenesis 137:154 The envelope (Env) glycoprotein of HIV is an important determinant of viral pathogenesis. 24265318 4 23 theme primary 451:457 arg1 Envs 459:462 primary Envs 451:462 primary Envs derived from HIV-infected patients 451:497 This raises the question of whether primary Envs derived from HIV-infected patients are capable of inducing bystander apoptosis and whether specific Env signatures are associated with this phenomenon. 24265318 11 24 theme bystander 1785:1793 arg1 phenotype 1814:1822 the bystander apoptosis-inducing phenotype 1781:1822 the bystander apoptosis-inducing phenotype 1781:1822 Furthermore, we identify specific genetic signatures within the Env that may be associated with the bystander apoptosis-inducing phenotype. 24265318 7 25 theme virion 1242:1247 arg1 infectivity 1249:1259 virion infectivity 1242:1259 virion infectivity 1242:1259 Our studies show that primary Envs vary considerably in their bystander apoptosis-inducing potential, a phenomenon that correlates inversely with putative N-linked glycosylation sites and positively with virion infectivity. 24265318 5 26 theme throughput 636:645 arg1 assay 647:651 a high throughput assay 629:651 a high throughput assay to determine the bystander apoptosis inducing activity of a panel of primary Envs 629:733 We developed a high throughput assay to determine the bystander apoptosis inducing activity of a panel of primary Envs. 24265318 6 27 theme viral 987:991 arg1 Env 993:995 the viral Env 983:995 the viral Env 983:995 We tested 38 different Envs for bystander apoptosis, virion infectivity, neutralizing antibody sensitivity, and putative N-linked glycosylation sites along with a comprehensive sequence analysis to determine if specific sequence signatures within the viral Env are associated with bystander apoptosis. 24265318 1 28 theme envelope 71:78 arg1 glycoprotein 86:97 The envelope (Env) glycoprotein 67:97 The envelope (Env) glycoprotein of HIV 67:104 The envelope (Env) glycoprotein of HIV is an important determinant of viral pathogenesis. 24265318 1 28 theme envelope 71:78 arg1 determinant 122:132 an important determinant 109:132 an important determinant of viral pathogenesis 109:154 The envelope (Env) glycoprotein of HIV is an important determinant of viral pathogenesis. 24265318 3 29 theme laboratory-adapted 380:397 arg1 isolates 405:412 laboratory-adapted HIV-1 isolates 380:412 laboratory-adapted HIV-1 isolates 380:412 However, most of the studies testing this phenomenon have been conducted with laboratory-adapted HIV-1 isolates. 24265318 1 30 theme Env 81:83 arg1 glycoprotein 86:97 The envelope (Env) glycoprotein 67:97 The envelope (Env) glycoprotein of HIV 67:104 The envelope (Env) glycoprotein of HIV is an important determinant of viral pathogenesis. 24265318 1 30 theme Env 81:83 arg1 determinant 122:132 an important determinant 109:132 an important determinant of viral pathogenesis 109:154 The envelope (Env) glycoprotein of HIV is an important determinant of viral pathogenesis. 24265318 0 31 theme Genetic 0:6 arg1 signatures 8:17 Genetic signatures 0:17 Genetic signatures of HIV-1 envelope-mediated bystander apoptosis 0:64 Genetic signatures of HIV-1 envelope-mediated bystander apoptosis. 24265318 6 32 link N-linked 857:864 arg1 sites 880:884 putative N-linked glycosylation sites 848:884 putative N-linked glycosylation sites 848:884 We tested 38 different Envs for bystander apoptosis, virion infectivity, neutralizing antibody sensitivity, and putative N-linked glycosylation sites along with a comprehensive sequence analysis to determine if specific sequence signatures within the viral Env are associated with bystander apoptosis. 24265318 2 33 theme evidence 174:181 arg1 lines 165:169 Several lines 157:169 Several lines of evidence 157:181 Several lines of evidence support the role of HIV-1 Env in inducing bystander apoptosis that may be a contributing factor in CD4(+) T cell loss. 24265318 1 34 theme HIV 102:104 arg1 glycoprotein 86:97 The envelope (Env) glycoprotein 67:97 The envelope (Env) glycoprotein of HIV 67:104 The envelope (Env) glycoprotein of HIV is an important determinant of viral pathogenesis. 24265318 1 34 theme HIV 102:104 arg1 determinant 122:132 an important determinant 109:132 an important determinant of viral pathogenesis 109:154 The envelope (Env) glycoprotein of HIV is an important determinant of viral pathogenesis. 24265318 4 35 theme bystander 523:531 arg1 apoptosis 533:541 bystander apoptosis 523:541 bystander apoptosis 523:541 This raises the question of whether primary Envs derived from HIV-infected patients are capable of inducing bystander apoptosis and whether specific Env signatures are associated with this phenomenon. 24265318 11 36 theme genetic 1719:1725 arg1 signatures 1727:1736 specific genetic signatures 1710:1736 specific genetic signatures within the Env that may be associated with the bystander apoptosis-inducing phenotype 1710:1822 Furthermore, we identify specific genetic signatures within the Env that may be associated with the bystander apoptosis-inducing phenotype. 24265318 0 37 theme envelope-mediated 28:44 arg1 apoptosis 56:64 HIV-1 envelope-mediated bystander apoptosis 22:64 HIV-1 envelope-mediated bystander apoptosis 22:64 Genetic signatures of HIV-1 envelope-mediated bystander apoptosis. 24265318 4 38 theme HIV-infected 477:488 arg1 patients 490:497 HIV-infected patients 477:497 HIV-infected patients 477:497 This raises the question of whether primary Envs derived from HIV-infected patients are capable of inducing bystander apoptosis and whether specific Env signatures are associated with this phenomenon. 24265318 2 39 theme Several 157:163 arg1 lines 165:169 Several lines 157:169 Several lines of evidence 157:181 Several lines of evidence support the role of HIV-1 Env in inducing bystander apoptosis that may be a contributing factor in CD4(+) T cell loss. 24265318 0 40 theme apoptosis 56:64 arg1 signatures 8:17 Genetic signatures 0:17 Genetic signatures of HIV-1 envelope-mediated bystander apoptosis 0:64 Genetic signatures of HIV-1 envelope-mediated bystander apoptosis. 24265318 6 41 theme neutralizing 809:820 arg1 sensitivity 831:841 neutralizing antibody sensitivity 809:841 neutralizing antibody sensitivity 809:841 We tested 38 different Envs for bystander apoptosis, virion infectivity, neutralizing antibody sensitivity, and putative N-linked glycosylation sites along with a comprehensive sequence analysis to determine if specific sequence signatures within the viral Env are associated with bystander apoptosis. 24265318 2 42 theme bystander 225:233 arg1 apoptosis 235:243 bystander apoptosis 225:243 bystander apoptosis that may be a contributing factor in CD4(+) T cell loss 225:299 Several lines of evidence support the role of HIV-1 Env in inducing bystander apoptosis that may be a contributing factor in CD4(+) T cell loss. 24265318 2 42 theme bystander 225:233 arg1 factor 272:277 a contributing factor 257:277 a contributing factor 257:277 Several lines of evidence support the role of HIV-1 Env in inducing bystander apoptosis that may be a contributing factor in CD4(+) T cell loss. 24265318 4 43 attach derived 464:470 arg2 Envs 459:462 primary Envs 451:462 primary Envs derived from HIV-infected patients 451:497 This raises the question of whether primary Envs derived from HIV-infected patients are capable of inducing bystander apoptosis and whether specific Env signatures are associated with this phenomenon. 24265318 4 43 attach derived 464:470 arg1 patients 490:497 HIV-infected patients 477:497 HIV-infected patients 477:497 This raises the question of whether primary Envs derived from HIV-infected patients are capable of inducing bystander apoptosis and whether specific Env signatures are associated with this phenomenon. 24265318 8 44 theme apoptosis 1470:1478 arg1 induction 1480:1488 bystander apoptosis induction 1460:1488 bystander apoptosis induction 1460:1488 By use of a novel phylogenetic analysis that avoids subtype bias coupled with structural considerations, we found specific residues like Arg-476 and Asn-425 that were associated with differences in bystander apoptosis induction. 24265318 7 45 theme glycosylation 1202:1214 arg1 sites 1216:1220 putative N-linked glycosylation sites 1184:1220 putative N-linked glycosylation sites 1184:1220 Our studies show that primary Envs vary considerably in their bystander apoptosis-inducing potential, a phenomenon that correlates inversely with putative N-linked glycosylation sites and positively with virion infectivity. 24265318 10 46 theme primary 1619:1625 arg1 Envs 1630:1633 primary R5 Envs 1619:1633 primary R5 Envs 1619:1633 These data demonstrate for the first time the potential of primary R5 Envs to mediate bystander apoptosis in CD4(+) T cells. 24265318 5 47 theme high 631:634 arg1 assay 647:651 a high throughput assay 629:651 a high throughput assay to determine the bystander apoptosis inducing activity of a panel of primary Envs 629:733 We developed a high throughput assay to determine the bystander apoptosis inducing activity of a panel of primary Envs. 24265318 10 48 from apoptosis 1656:1664 arg1 cells 1678:1682 CD4(+) T cells 1669:1682 CD4(+) T cells 1669:1682 These data demonstrate for the first time the potential of primary R5 Envs to mediate bystander apoptosis in CD4(+) T cells. 24265318 4 49 theme specific 555:562 arg1 signatures 568:577 specific Env signatures 555:577 specific Env signatures 555:577 This raises the question of whether primary Envs derived from HIV-infected patients are capable of inducing bystander apoptosis and whether specific Env signatures are associated with this phenomenon. 24265318 6 50 theme N-linked 857:864 arg1 sites 880:884 putative N-linked glycosylation sites 848:884 putative N-linked glycosylation sites 848:884 We tested 38 different Envs for bystander apoptosis, virion infectivity, neutralizing antibody sensitivity, and putative N-linked glycosylation sites along with a comprehensive sequence analysis to determine if specific sequence signatures within the viral Env are associated with bystander apoptosis. 24265318 6 51 theme different 749:757 arg1 Envs 759:762 38 different Envs 746:762 38 different Envs for bystander apoptosis 746:786 We tested 38 different Envs for bystander apoptosis, virion infectivity, neutralizing antibody sensitivity, and putative N-linked glycosylation sites along with a comprehensive sequence analysis to determine if specific sequence signatures within the viral Env are associated with bystander apoptosis. 24265318 10 52 theme Envs 1630:1633 arg1 potential 1606:1614 the potential 1602:1614 the potential of primary R5 Envs to mediate bystander apoptosis in CD4(+) T cells 1602:1682 These data demonstrate for the first time the potential of primary R5 Envs to mediate bystander apoptosis in CD4(+) T cells. 24265318 5 53 theme bystander 670:678 arg1 activity 699:706 the bystander apoptosis inducing activity 666:706 the bystander apoptosis inducing activity of a panel of primary Envs 666:733 We developed a high throughput assay to determine the bystander apoptosis inducing activity of a panel of primary Envs. 24265318 2 54 theme CD4 282:284 arg1 loss 296:299 CD4(+) T cell loss 282:299 CD4(+) T cell loss 282:299 Several lines of evidence support the role of HIV-1 Env in inducing bystander apoptosis that may be a contributing factor in CD4(+) T cell loss. 24265318 6 55 theme specific 947:954 arg1 signatures 965:974 specific sequence signatures 947:974 specific sequence signatures within the viral Env 947:995 We tested 38 different Envs for bystander apoptosis, virion infectivity, neutralizing antibody sensitivity, and putative N-linked glycosylation sites along with a comprehensive sequence analysis to determine if specific sequence signatures within the viral Env are associated with bystander apoptosis. 24265318 8 56 theme novel 1274:1278 arg1 analysis 1293:1300 a novel phylogenetic analysis 1272:1300 a novel phylogenetic analysis that avoids subtype bias coupled with structural considerations 1272:1364 By use of a novel phylogenetic analysis that avoids subtype bias coupled with structural considerations, we found specific residues like Arg-476 and Asn-425 that were associated with differences in bystander apoptosis induction. 24265318 10 57 theme CD4 1669:1671 arg1 cells 1678:1682 CD4(+) T cells 1669:1682 CD4(+) T cells 1669:1682 These data demonstrate for the first time the potential of primary R5 Envs to mediate bystander apoptosis in CD4(+) T cells. 24265318 5 58 theme inducing 690:697 arg1 activity 699:706 the bystander apoptosis inducing activity 666:706 the bystander apoptosis inducing activity of a panel of primary Envs 666:733 We developed a high throughput assay to determine the bystander apoptosis inducing activity of a panel of primary Envs. 24265318 8 59 from differences 1445:1455 arg1 induction 1480:1488 bystander apoptosis induction 1460:1488 bystander apoptosis induction 1460:1488 By use of a novel phylogenetic analysis that avoids subtype bias coupled with structural considerations, we found specific residues like Arg-476 and Asn-425 that were associated with differences in bystander apoptosis induction. 24265318 8 60 theme analysis 1293:1300 arg1 use 1265:1267 use 1265:1267 use of a novel phylogenetic analysis that avoids subtype bias coupled with structural considerations 1265:1364 By use of a novel phylogenetic analysis that avoids subtype bias coupled with structural considerations, we found specific residues like Arg-476 and Asn-425 that were associated with differences in bystander apoptosis induction. 24265318 2 61 theme Env 209:211 arg1 role 195:198 the role 191:198 the role of HIV-1 Env in inducing bystander apoptosis that may be a contributing factor in CD4(+) T cell loss 191:299 Several lines of evidence support the role of HIV-1 Env in inducing bystander apoptosis that may be a contributing factor in CD4(+) T cell loss. 24265318 7 62 theme primary 1060:1066 arg1 Envs 1068:1071 primary Envs 1060:1071 primary Envs 1060:1071 Our studies show that primary Envs vary considerably in their bystander apoptosis-inducing potential, a phenomenon that correlates inversely with putative N-linked glycosylation sites and positively with virion infectivity. 24265318 6 63 gly glycosylation 866:878 arg2 sites 880:884 putative N-linked glycosylation sites 848:884 putative N-linked glycosylation sites 848:884 We tested 38 different Envs for bystander apoptosis, virion infectivity, neutralizing antibody sensitivity, and putative N-linked glycosylation sites along with a comprehensive sequence analysis to determine if specific sequence signatures within the viral Env are associated with bystander apoptosis. 24265318 1 64 theme important 112:120 arg1 glycoprotein 86:97 The envelope (Env) glycoprotein 67:97 The envelope (Env) glycoprotein of HIV 67:104 The envelope (Env) glycoprotein of HIV is an important determinant of viral pathogenesis. 24265318 1 64 theme important 112:120 arg1 determinant 122:132 an important determinant 109:132 an important determinant of viral pathogenesis 109:154 The envelope (Env) glycoprotein of HIV is an important determinant of viral pathogenesis. 24265318 6 65 theme bystander 1017:1025 arg1 apoptosis 1027:1035 bystander apoptosis 1017:1035 bystander apoptosis 1017:1035 We tested 38 different Envs for bystander apoptosis, virion infectivity, neutralizing antibody sensitivity, and putative N-linked glycosylation sites along with a comprehensive sequence analysis to determine if specific sequence signatures within the viral Env are associated with bystander apoptosis. 24265318 2 66 theme T 289:289 arg1 loss 296:299 CD4(+) T cell loss 282:299 CD4(+) T cell loss 282:299 Several lines of evidence support the role of HIV-1 Env in inducing bystander apoptosis that may be a contributing factor in CD4(+) T cell loss. 24265318 5 67 theme primary 722:728 arg1 Envs 730:733 primary Envs 722:733 primary Envs 722:733 We developed a high throughput assay to determine the bystander apoptosis inducing activity of a panel of primary Envs. 24265318 1 68 theme pathogenesis 143:154 arg1 glycoprotein 86:97 The envelope (Env) glycoprotein 67:97 The envelope (Env) glycoprotein of HIV 67:104 The envelope (Env) glycoprotein of HIV is an important determinant of viral pathogenesis. 24265318 1 68 theme pathogenesis 143:154 arg1 determinant 122:132 an important determinant 109:132 an important determinant of viral pathogenesis 109:154 The envelope (Env) glycoprotein of HIV is an important determinant of viral pathogenesis. 24265318 11 69 theme apoptosis-inducing 1795:1812 arg1 phenotype 1814:1822 the bystander apoptosis-inducing phenotype 1781:1822 the bystander apoptosis-inducing phenotype 1781:1822 Furthermore, we identify specific genetic signatures within the Env that may be associated with the bystander apoptosis-inducing phenotype. 24265318 1 70 gly glycoprotein 86:97 arg1 glycoprotein 86:97 The envelope (Env) glycoprotein 67:97 The envelope (Env) glycoprotein of HIV 67:104 The envelope (Env) glycoprotein of HIV is an important determinant of viral pathogenesis. 24265318 1 70 gly glycoprotein 86:97 arg1 determinant 122:132 an important determinant 109:132 an important determinant of viral pathogenesis 109:154 The envelope (Env) glycoprotein of HIV is an important determinant of viral pathogenesis. 24265318 5 71 theme panel 713:717 arg1 activity 699:706 the bystander apoptosis inducing activity 666:706 the bystander apoptosis inducing activity of a panel of primary Envs 666:733 We developed a high throughput assay to determine the bystander apoptosis inducing activity of a panel of primary Envs. 24265318 8 72 theme specific 1376:1383 arg1 residues 1385:1392 specific residues 1376:1392 specific residues like Arg-476 and Asn-425 that were associated with differences in bystander apoptosis induction 1376:1488 By use of a novel phylogenetic analysis that avoids subtype bias coupled with structural considerations, we found specific residues like Arg-476 and Asn-425 that were associated with differences in bystander apoptosis induction. 24265318 3 73 theme HIV-1 399:403 arg1 isolates 405:412 laboratory-adapted HIV-1 isolates 380:412 laboratory-adapted HIV-1 isolates 380:412 However, most of the studies testing this phenomenon have been conducted with laboratory-adapted HIV-1 isolates. 24265318 7 74 theme putative 1184:1191 arg1 sites 1216:1220 putative N-linked glycosylation sites 1184:1220 putative N-linked glycosylation sites 1184:1220 Our studies show that primary Envs vary considerably in their bystander apoptosis-inducing potential, a phenomenon that correlates inversely with putative N-linked glycosylation sites and positively with virion infectivity. 24265318 0 75 theme HIV-1 22:26 arg1 apoptosis 56:64 HIV-1 envelope-mediated bystander apoptosis 22:64 HIV-1 envelope-mediated bystander apoptosis 22:64 Genetic signatures of HIV-1 envelope-mediated bystander apoptosis. 24265318 11 76 theme specific 1710:1717 arg1 signatures 1727:1736 specific genetic signatures 1710:1736 specific genetic signatures within the Env that may be associated with the bystander apoptosis-inducing phenotype 1710:1822 Furthermore, we identify specific genetic signatures within the Env that may be associated with the bystander apoptosis-inducing phenotype. 24265318 0 77 theme bystander 46:54 arg1 apoptosis 56:64 HIV-1 envelope-mediated bystander apoptosis 22:64 HIV-1 envelope-mediated bystander apoptosis 22:64 Genetic signatures of HIV-1 envelope-mediated bystander apoptosis. 24265318 10 78 theme T 1676:1676 arg1 cells 1678:1682 CD4(+) T cells 1669:1682 CD4(+) T cells 1669:1682 These data demonstrate for the first time the potential of primary R5 Envs to mediate bystander apoptosis in CD4(+) T cells. 24265318 6 79 theme antibody 822:829 arg1 sensitivity 831:841 neutralizing antibody sensitivity 809:841 neutralizing antibody sensitivity 809:841 We tested 38 different Envs for bystander apoptosis, virion infectivity, neutralizing antibody sensitivity, and putative N-linked glycosylation sites along with a comprehensive sequence analysis to determine if specific sequence signatures within the viral Env are associated with bystander apoptosis. 24265318 6 80 theme comprehensive 899:911 arg1 analysis 922:929 a comprehensive sequence analysis 897:929 a comprehensive sequence analysis to determine if specific sequence signatures within the viral Env are associated with bystander apoptosis 897:1035 We tested 38 different Envs for bystander apoptosis, virion infectivity, neutralizing antibody sensitivity, and putative N-linked glycosylation sites along with a comprehensive sequence analysis to determine if specific sequence signatures within the viral Env are associated with bystander apoptosis. 24265318 2 81 theme cell 291:294 arg1 loss 296:299 CD4(+) T cell loss 282:299 CD4(+) T cell loss 282:299 Several lines of evidence support the role of HIV-1 Env in inducing bystander apoptosis that may be a contributing factor in CD4(+) T cell loss. 24265318 7 82 gly glycosylation 1202:1214 arg2 sites 1216:1220 putative N-linked glycosylation sites 1184:1220 putative N-linked glycosylation sites 1184:1220 Our studies show that primary Envs vary considerably in their bystander apoptosis-inducing potential, a phenomenon that correlates inversely with putative N-linked glycosylation sites and positively with virion infectivity. 24265318 6 83 theme virion 789:794 arg1 infectivity 796:806 virion infectivity 789:806 virion infectivity 789:806 We tested 38 different Envs for bystander apoptosis, virion infectivity, neutralizing antibody sensitivity, and putative N-linked glycosylation sites along with a comprehensive sequence analysis to determine if specific sequence signatures within the viral Env are associated with bystander apoptosis. 24265318 10 84 theme first 1591:1595 arg1 time 1597:1600 the first time 1587:1600 the first time 1587:1600 These data demonstrate for the first time the potential of primary R5 Envs to mediate bystander apoptosis in CD4(+) T cells. 24265318 8 85 theme bystander 1460:1468 arg1 induction 1480:1488 bystander apoptosis induction 1460:1488 bystander apoptosis induction 1460:1488 By use of a novel phylogenetic analysis that avoids subtype bias coupled with structural considerations, we found specific residues like Arg-476 and Asn-425 that were associated with differences in bystander apoptosis induction. 25326145 4 0 theme protein 745:751 arg1 C 753:753 protein C 745:753 |protein C (vitamin K-dependent protein C precursor, gi||62078422)| 745:808 |Tandem mass spectra of the peptides obtained following trypsin digestion and liquid chromatography identified this protein to be protein C (vitamin K-dependent protein C precursor, gi||62078422) with 100% probability.| 25326145 9 1 theme anti-coagulant 1779:1792 arg1 properties 1794:1803 amidolytic and anti-coagulant properties 1764:1803 amidolytic and anti-coagulant properties 1764:1803 CONCLUSIONS: These studies showed that CnPC could be purified from plasma using HPC4 and that this protein showed amidolytic and anti-coagulant properties upon activation with Protac. 25326145 6 2 theme bond 1307:1310 arg1 salt 1384:1387 an amide bond [H-D-(γ-carbobenzoxyl)-lysyl-prolyl-arginine-paranitroanilide diacetate salt] 1298:1388 an amide bond [H-D-(γ-carbobenzoxyl)-lysyl-prolyl-arginine-paranitroanilide diacetate salt] 1298:1388 Following incubation with Protac (a specific activator of protein C), the heavy chain showed a slight decrease in molecular size and amidolytic activity measured by a synthetic chromogenic substrate containing an amide bond [H-D-(γ-carbobenzoxyl)-lysyl-prolyl-arginine-paranitroanilide diacetate salt]. 25326145 2 3 dep characterize 442:453 arg1 2 436:436 2 436:436 2 436:436 The goals of this study were (1) to purify protein C from fresh frozen canine plasma by barium chloride and ammonium sulphate precipitation, followed by immunoaffinity chromatography using a monoclonal mouse antibody against human protein C (HPC4) and (2) to characterize this protein's structure. 25326145 3 4 theme ~ 605:605 arg1 kDa 610:612 ~ 25 kDa 605:612 ~ 25 kDa 605:612 RESULTS: The purified protein contained three glycosylated forms of a heavy chain (~49 kDa) and a glycosylated light chain (~ 25 kDa). 25326145 3 4 theme ~ 605:605 arg1 chain 598:602 a glycosylated light chain 577:602 a glycosylated light chain (~ 25 kDa) 577:613 RESULTS: The purified protein contained three glycosylated forms of a heavy chain (~49 kDa) and a glycosylated light chain (~ 25 kDa). 25326145 6 5 theme specific 1124:1131 arg1 activator 1133:1141 a specific activator 1122:1141 a specific activator of protein C 1122:1154 Following incubation with Protac (a specific activator of protein C), the heavy chain showed a slight decrease in molecular size and amidolytic activity measured by a synthetic chromogenic substrate containing an amide bond [H-D-(γ-carbobenzoxyl)-lysyl-prolyl-arginine-paranitroanilide diacetate salt]. 25326145 8 6 theme canine 1604:1609 arg1 plasma 1611:1616 canine plasma 1604:1616 canine plasma 1604:1616 The purified protein showed concentration-dependent anti-factor V and anti-factor VIII activities in canine plasma in coagulometric factor assays. 25326145 5 7 theme 18O-labeled 1069:1079 arg1 water 1081:1085 18O-labeled water 1069:1085 18O-labeled water 1069:1085 Three glycosylation sites (Asn139, Asn202, and Asn350) were identified by detection of peptides containing an N-linked glycosylation consensus sequon with a 3-dalton increase in mass following incubation of the protein with PNGase F in 18O-labeled water. 25326145 3 8 theme chain 598:602 arg1 forms 540:544 three glycosylated forms 521:544 three glycosylated forms of a heavy chain (~49 kDa) and a glycosylated light chain (~ 25 kDa) 521:613 RESULTS: The purified protein contained three glycosylated forms of a heavy chain (~49 kDa) and a glycosylated light chain (~ 25 kDa). 25326145 5 9 contain containing 929:938 arg1 peptides 920:927 peptides 920:927 peptides containing an N-linked glycosylation consensus sequon with a 3-dalton increase in mass following incubation of the protein with PNGase F in 18O-labeled water 920:1085 Three glycosylation sites (Asn139, Asn202, and Asn350) were identified by detection of peptides containing an N-linked glycosylation consensus sequon with a 3-dalton increase in mass following incubation of the protein with PNGase F in 18O-labeled water. 25326145 5 9 contain containing 929:938 arg2 sequon 976:981 an N-linked glycosylation consensus sequon 940:981 an N-linked glycosylation consensus sequon 940:981 Three glycosylation sites (Asn139, Asn202, and Asn350) were identified by detection of peptides containing an N-linked glycosylation consensus sequon with a 3-dalton increase in mass following incubation of the protein with PNGase F in 18O-labeled water. 25326145 8 10 theme factor 1635:1640 arg1 assays 1642:1647 coagulometric factor assays 1621:1647 coagulometric factor assays 1621:1647 The purified protein showed concentration-dependent anti-factor V and anti-factor VIII activities in canine plasma in coagulometric factor assays. 25326145 2 11 dep purify 219:224 arg1 1 213:213 1 213:213 1 213:213 The goals of this study were (1) to purify protein C from fresh frozen canine plasma by barium chloride and ammonium sulphate precipitation, followed by immunoaffinity chromatography using a monoclonal mouse antibody against human protein C (HPC4) and (2) to characterize this protein's structure. 25326145 5 12 from F 1064:1064 arg1 water 1081:1085 18O-labeled water 1069:1085 18O-labeled water 1069:1085 Three glycosylation sites (Asn139, Asn202, and Asn350) were identified by detection of peptides containing an N-linked glycosylation consensus sequon with a 3-dalton increase in mass following incubation of the protein with PNGase F in 18O-labeled water. 25326145 4 13 theme K-dependent 764:774 arg1 C 784:784 vitamin K-dependent protein C 756:784 vitamin K-dependent protein C precursor 756:794 |Tandem mass spectra of the peptides obtained following trypsin digestion and liquid chromatography identified this protein to be protein C (vitamin K-dependent protein C precursor, gi||62078422) with 100% probability.| 25326145 4 14 theme C 784:784 arg1 |gi||62078422| 797:807 |gi||62078422| 797:807 |gi||62078422| 797:807 |Tandem mass spectra of the peptides obtained following trypsin digestion and liquid chromatography identified this protein to be protein C (vitamin K-dependent protein C precursor, gi||62078422) with 100% probability.| 25326145 4 14 theme C 784:784 arg1 precursor 786:794 vitamin K-dependent protein C precursor 756:794 vitamin K-dependent protein C precursor 756:794 |Tandem mass spectra of the peptides obtained following trypsin digestion and liquid chromatography identified this protein to be protein C (vitamin K-dependent protein C precursor, gi||62078422) with 100% probability.| 25326145 6 15 theme C 1154:1154 arg1 activator 1133:1141 a specific activator 1122:1141 a specific activator of protein C 1122:1154 Following incubation with Protac (a specific activator of protein C), the heavy chain showed a slight decrease in molecular size and amidolytic activity measured by a synthetic chromogenic substrate containing an amide bond [H-D-(γ-carbobenzoxyl)-lysyl-prolyl-arginine-paranitroanilide diacetate salt]. 25326145 2 16 theme study 201:205 arg1 goals 187:191 The goals 183:191 The goals of this study 183:205 The goals of this study were (1) to purify protein C from fresh frozen canine plasma by barium chloride and ammonium sulphate precipitation, followed by immunoaffinity chromatography using a monoclonal mouse antibody against human protein C (HPC4) and (2) to characterize this protein's structure. 25326145 1 17 theme protein 119:125 arg1 CnPC 130:133 CnPC 130:133 CnPC 130:133 BACKGROUND: In order to characterize the functional properties of canine protein C (CnPC), the zymogen needs to be purified from plasma. 25326145 1 17 theme protein 119:125 arg1 C 127:127 canine protein C 112:127 canine protein C (CnPC) 112:134 BACKGROUND: In order to characterize the functional properties of canine protein C (CnPC), the zymogen needs to be purified from plasma. 25326145 8 18 theme VIII 1585:1588 arg1 activities 1590:1599 concentration-dependent anti-factor V and anti-factor VIII activities 1531:1599 concentration-dependent anti-factor V and anti-factor VIII activities in canine plasma 1531:1616 The purified protein showed concentration-dependent anti-factor V and anti-factor VIII activities in canine plasma in coagulometric factor assays. 25326145 6 19 theme amidolytic 1221:1230 arg1 activity 1232:1239 amidolytic activity 1221:1239 amidolytic activity 1221:1239 Following incubation with Protac (a specific activator of protein C), the heavy chain showed a slight decrease in molecular size and amidolytic activity measured by a synthetic chromogenic substrate containing an amide bond [H-D-(γ-carbobenzoxyl)-lysyl-prolyl-arginine-paranitroanilide diacetate salt]. 25326145 6 20 theme chromogenic 1265:1275 arg1 substrate 1277:1285 a synthetic chromogenic substrate 1253:1285 a synthetic chromogenic substrate containing an amide bond [H-D-(γ-carbobenzoxyl)-lysyl-prolyl-arginine-paranitroanilide diacetate salt] 1253:1388 Following incubation with Protac (a specific activator of protein C), the heavy chain showed a slight decrease in molecular size and amidolytic activity measured by a synthetic chromogenic substrate containing an amide bond [H-D-(γ-carbobenzoxyl)-lysyl-prolyl-arginine-paranitroanilide diacetate salt]. 25326145 7 21 theme protein 1455:1461 arg1 preparation 1463:1473 the final protein preparation 1445:1473 the final protein preparation 1445:1473 The amidolytic activity was increased by ~303-fold in the final protein preparation compared to that in plasma. 25326145 5 22 theme 3-dalton 990:997 arg1 increase 999:1006 a 3-dalton increase 988:1006 a 3-dalton increase in mass following incubation of the protein with PNGase F in 18O-labeled water 988:1085 Three glycosylation sites (Asn139, Asn202, and Asn350) were identified by detection of peptides containing an N-linked glycosylation consensus sequon with a 3-dalton increase in mass following incubation of the protein with PNGase F in 18O-labeled water. 25326145 4 23 theme 100 815:817 arg1 % 818:818 % 818:818 % 818:818 |Tandem mass spectra of the peptides obtained following trypsin digestion and liquid chromatography identified this protein to be protein C (vitamin K-dependent protein C precursor, gi||62078422) with 100% probability.| 25326145 5 24 theme N-linked 943:950 arg1 sequon 976:981 an N-linked glycosylation consensus sequon 940:981 an N-linked glycosylation consensus sequon 940:981 Three glycosylation sites (Asn139, Asn202, and Asn350) were identified by detection of peptides containing an N-linked glycosylation consensus sequon with a 3-dalton increase in mass following incubation of the protein with PNGase F in 18O-labeled water. 25326145 0 25 from plasma 38:43 arg1 Purification 0:11 Purification 0:11 Purification of protein C from canine plasma. 0:44 Purification of protein C from canine plasma. 25326145 6 26 theme slight 1183:1188 arg1 decrease 1190:1197 a slight decrease 1181:1197 a slight decrease in molecular size and amidolytic activity measured by a synthetic chromogenic substrate containing an amide bond [H-D-(γ-carbobenzoxyl)-lysyl-prolyl-arginine-paranitroanilide diacetate salt] 1181:1388 Following incubation with Protac (a specific activator of protein C), the heavy chain showed a slight decrease in molecular size and amidolytic activity measured by a synthetic chromogenic substrate containing an amide bond [H-D-(γ-carbobenzoxyl)-lysyl-prolyl-arginine-paranitroanilide diacetate salt]. 25326145 5 27 theme consensus 966:974 arg1 sequon 976:981 an N-linked glycosylation consensus sequon 940:981 an N-linked glycosylation consensus sequon 940:981 Three glycosylation sites (Asn139, Asn202, and Asn350) were identified by detection of peptides containing an N-linked glycosylation consensus sequon with a 3-dalton increase in mass following incubation of the protein with PNGase F in 18O-labeled water. 25326145 0 28 theme canine 31:36 arg1 plasma 38:43 canine plasma 31:43 canine plasma 31:43 Purification of protein C from canine plasma. 25326145 5 29 link N-linked 943:950 arg1 sequon 976:981 an N-linked glycosylation consensus sequon 940:981 an N-linked glycosylation consensus sequon 940:981 Three glycosylation sites (Asn139, Asn202, and Asn350) were identified by detection of peptides containing an N-linked glycosylation consensus sequon with a 3-dalton increase in mass following incubation of the protein with PNGase F in 18O-labeled water. 25326145 2 30 theme mouse 385:389 arg1 antibody 391:398 a monoclonal mouse antibody 372:398 a monoclonal mouse antibody against human protein C 372:422 The goals of this study were (1) to purify protein C from fresh frozen canine plasma by barium chloride and ammonium sulphate precipitation, followed by immunoaffinity chromatography using a monoclonal mouse antibody against human protein C (HPC4) and (2) to characterize this protein's structure. 25326145 8 31 from activities 1590:1599 arg1 plasma 1611:1616 canine plasma 1604:1616 canine plasma 1604:1616 The purified protein showed concentration-dependent anti-factor V and anti-factor VIII activities in canine plasma in coagulometric factor assays. 25326145 2 32 theme sulphate 300:307 arg1 precipitation 309:321 ammonium sulphate precipitation 291:321 ammonium sulphate precipitation 291:321 The goals of this study were (1) to purify protein C from fresh frozen canine plasma by barium chloride and ammonium sulphate precipitation, followed by immunoaffinity chromatography using a monoclonal mouse antibody against human protein C (HPC4) and (2) to characterize this protein's structure. 25326145 4 33 theme Tandem 616:621 arg1 spectra 628:634 Tandem mass spectra 616:634 Tandem mass spectra of the peptides obtained following trypsin digestion and liquid chromatography 616:713 |Tandem mass spectra of the peptides obtained following trypsin digestion and liquid chromatography identified this protein to be protein C (vitamin K-dependent protein C precursor, gi||62078422) with 100% probability.| 25326145 0 34 theme protein 16:22 arg1 C 24:24 protein C 16:24 protein C 16:24 Purification of protein C from canine plasma. 25326145 5 35 theme protein 1044:1050 arg1 incubation 1026:1035 incubation 1026:1035 incubation of the protein with PNGase F in 18O-labeled water 1026:1085 Three glycosylation sites (Asn139, Asn202, and Asn350) were identified by detection of peptides containing an N-linked glycosylation consensus sequon with a 3-dalton increase in mass following incubation of the protein with PNGase F in 18O-labeled water. 25326145 1 36 theme functional 87:96 arg1 properties 98:107 the functional properties 83:107 the functional properties of canine protein C (CnPC) 83:134 BACKGROUND: In order to characterize the functional properties of canine protein C (CnPC), the zymogen needs to be purified from plasma. 25326145 2 37 theme protein 414:420 arg1 C 422:422 human protein C 408:422 human protein C 408:422 The goals of this study were (1) to purify protein C from fresh frozen canine plasma by barium chloride and ammonium sulphate precipitation, followed by immunoaffinity chromatography using a monoclonal mouse antibody against human protein C (HPC4) and (2) to characterize this protein's structure. 25326145 3 38 theme chain 557:561 arg1 forms 540:544 three glycosylated forms 521:544 three glycosylated forms of a heavy chain (~49 kDa) and a glycosylated light chain (~ 25 kDa) 521:613 RESULTS: The purified protein contained three glycosylated forms of a heavy chain (~49 kDa) and a glycosylated light chain (~ 25 kDa). 25326145 5 39 from increase 999:1006 arg1 mass 1011:1014 mass 1011:1014 mass following incubation of the protein with PNGase F in 18O-labeled water 1011:1085 Three glycosylation sites (Asn139, Asn202, and Asn350) were identified by detection of peptides containing an N-linked glycosylation consensus sequon with a 3-dalton increase in mass following incubation of the protein with PNGase F in 18O-labeled water. 25326145 4 40 dep C 753:753 arg1 |gi||62078422| 797:807 |gi||62078422| 797:807 |gi||62078422| 797:807 |Tandem mass spectra of the peptides obtained following trypsin digestion and liquid chromatography identified this protein to be protein C (vitamin K-dependent protein C precursor, gi||62078422) with 100% probability.| 25326145 4 40 dep C 753:753 arg1 precursor 786:794 vitamin K-dependent protein C precursor 756:794 vitamin K-dependent protein C precursor 756:794 |Tandem mass spectra of the peptides obtained following trypsin digestion and liquid chromatography identified this protein to be protein C (vitamin K-dependent protein C precursor, gi||62078422) with 100% probability.| 25326145 7 41 theme amidolytic 1395:1404 arg1 activity 1406:1413 The amidolytic activity 1391:1413 The amidolytic activity 1391:1413 The amidolytic activity was increased by ~303-fold in the final protein preparation compared to that in plasma. 25326145 7 42 theme final 1449:1453 arg1 preparation 1463:1473 the final protein preparation 1445:1473 the final protein preparation 1445:1473 The amidolytic activity was increased by ~303-fold in the final protein preparation compared to that in plasma. 25326145 3 43 gly glycosylated 579:590 arg1 kDa 610:612 ~ 25 kDa 605:612 ~ 25 kDa 605:612 RESULTS: The purified protein contained three glycosylated forms of a heavy chain (~49 kDa) and a glycosylated light chain (~ 25 kDa). 25326145 3 43 gly glycosylated 579:590 arg1 chain 598:602 a glycosylated light chain 577:602 a glycosylated light chain (~ 25 kDa) 577:613 RESULTS: The purified protein contained three glycosylated forms of a heavy chain (~49 kDa) and a glycosylated light chain (~ 25 kDa). 25326145 6 44 contain containing 1287:1296 arg1 substrate 1277:1285 a synthetic chromogenic substrate 1253:1285 a synthetic chromogenic substrate containing an amide bond [H-D-(γ-carbobenzoxyl)-lysyl-prolyl-arginine-paranitroanilide diacetate salt] 1253:1388 Following incubation with Protac (a specific activator of protein C), the heavy chain showed a slight decrease in molecular size and amidolytic activity measured by a synthetic chromogenic substrate containing an amide bond [H-D-(γ-carbobenzoxyl)-lysyl-prolyl-arginine-paranitroanilide diacetate salt]. 25326145 6 44 contain containing 1287:1296 arg2 salt 1384:1387 an amide bond [H-D-(γ-carbobenzoxyl)-lysyl-prolyl-arginine-paranitroanilide diacetate salt] 1298:1388 an amide bond [H-D-(γ-carbobenzoxyl)-lysyl-prolyl-arginine-paranitroanilide diacetate salt] 1298:1388 Following incubation with Protac (a specific activator of protein C), the heavy chain showed a slight decrease in molecular size and amidolytic activity measured by a synthetic chromogenic substrate containing an amide bond [H-D-(γ-carbobenzoxyl)-lysyl-prolyl-arginine-paranitroanilide diacetate salt]. 25326145 2 45 theme frozen 247:252 arg1 plasma 261:266 fresh frozen canine plasma 241:266 fresh frozen canine plasma 241:266 The goals of this study were (1) to purify protein C from fresh frozen canine plasma by barium chloride and ammonium sulphate precipitation, followed by immunoaffinity chromatography using a monoclonal mouse antibody against human protein C (HPC4) and (2) to characterize this protein's structure. 25326145 6 46 theme -lysyl-prolyl-arginine-paranitroanilide 1334:1372 arg1 salt 1384:1387 an amide bond [H-D-(γ-carbobenzoxyl)-lysyl-prolyl-arginine-paranitroanilide diacetate salt] 1298:1388 an amide bond [H-D-(γ-carbobenzoxyl)-lysyl-prolyl-arginine-paranitroanilide diacetate salt] 1298:1388 Following incubation with Protac (a specific activator of protein C), the heavy chain showed a slight decrease in molecular size and amidolytic activity measured by a synthetic chromogenic substrate containing an amide bond [H-D-(γ-carbobenzoxyl)-lysyl-prolyl-arginine-paranitroanilide diacetate salt]. 25326145 3 47 contain contained 511:519 arg2 forms 540:544 three glycosylated forms 521:544 three glycosylated forms of a heavy chain (~49 kDa) and a glycosylated light chain (~ 25 kDa) 521:613 RESULTS: The purified protein contained three glycosylated forms of a heavy chain (~49 kDa) and a glycosylated light chain (~ 25 kDa). 25326145 3 47 contain contained 511:519 arg1 protein 503:509 The purified protein 490:509 The purified protein 490:509 RESULTS: The purified protein contained three glycosylated forms of a heavy chain (~49 kDa) and a glycosylated light chain (~ 25 kDa). 25326145 4 48 theme trypsin 671:677 arg1 digestion 679:687 trypsin digestion 671:687 trypsin digestion 671:687 |Tandem mass spectra of the peptides obtained following trypsin digestion and liquid chromatography identified this protein to be protein C (vitamin K-dependent protein C precursor, gi||62078422) with 100% probability.| 25326145 6 49 theme γ-carbobenzoxyl 1318:1332 arg1 salt 1384:1387 an amide bond [H-D-(γ-carbobenzoxyl)-lysyl-prolyl-arginine-paranitroanilide diacetate salt] 1298:1388 an amide bond [H-D-(γ-carbobenzoxyl)-lysyl-prolyl-arginine-paranitroanilide diacetate salt] 1298:1388 Following incubation with Protac (a specific activator of protein C), the heavy chain showed a slight decrease in molecular size and amidolytic activity measured by a synthetic chromogenic substrate containing an amide bond [H-D-(γ-carbobenzoxyl)-lysyl-prolyl-arginine-paranitroanilide diacetate salt]. 25326145 3 50 theme light 592:596 arg1 kDa 610:612 ~ 25 kDa 605:612 ~ 25 kDa 605:612 RESULTS: The purified protein contained three glycosylated forms of a heavy chain (~49 kDa) and a glycosylated light chain (~ 25 kDa). 25326145 3 50 theme light 592:596 arg1 chain 598:602 a glycosylated light chain 577:602 a glycosylated light chain (~ 25 kDa) 577:613 RESULTS: The purified protein contained three glycosylated forms of a heavy chain (~49 kDa) and a glycosylated light chain (~ 25 kDa). 25326145 6 51 theme protein 1146:1152 arg1 C 1154:1154 protein C 1146:1154 protein C 1146:1154 Following incubation with Protac (a specific activator of protein C), the heavy chain showed a slight decrease in molecular size and amidolytic activity measured by a synthetic chromogenic substrate containing an amide bond [H-D-(γ-carbobenzoxyl)-lysyl-prolyl-arginine-paranitroanilide diacetate salt]. 25326145 2 52 theme barium 271:276 arg1 chloride 278:285 barium chloride 271:285 barium chloride 271:285 The goals of this study were (1) to purify protein C from fresh frozen canine plasma by barium chloride and ammonium sulphate precipitation, followed by immunoaffinity chromatography using a monoclonal mouse antibody against human protein C (HPC4) and (2) to characterize this protein's structure. 25326145 6 53 theme [H-D- 1312:1316 arg1 salt 1384:1387 an amide bond [H-D-(γ-carbobenzoxyl)-lysyl-prolyl-arginine-paranitroanilide diacetate salt] 1298:1388 an amide bond [H-D-(γ-carbobenzoxyl)-lysyl-prolyl-arginine-paranitroanilide diacetate salt] 1298:1388 Following incubation with Protac (a specific activator of protein C), the heavy chain showed a slight decrease in molecular size and amidolytic activity measured by a synthetic chromogenic substrate containing an amide bond [H-D-(γ-carbobenzoxyl)-lysyl-prolyl-arginine-paranitroanilide diacetate salt]. 25326145 5 54 theme PNGase 1057:1062 arg1 F 1064:1064 PNGase F 1057:1064 PNGase F in 18O-labeled water 1057:1085 Three glycosylation sites (Asn139, Asn202, and Asn350) were identified by detection of peptides containing an N-linked glycosylation consensus sequon with a 3-dalton increase in mass following incubation of the protein with PNGase F in 18O-labeled water. 25326145 5 55 with incubation 1026:1035 arg1 F 1064:1064 PNGase F 1057:1064 PNGase F in 18O-labeled water 1057:1085 Three glycosylation sites (Asn139, Asn202, and Asn350) were identified by detection of peptides containing an N-linked glycosylation consensus sequon with a 3-dalton increase in mass following incubation of the protein with PNGase F in 18O-labeled water. 25326145 6 56 theme amide 1301:1305 arg1 salt 1384:1387 an amide bond [H-D-(γ-carbobenzoxyl)-lysyl-prolyl-arginine-paranitroanilide diacetate salt] 1298:1388 an amide bond [H-D-(γ-carbobenzoxyl)-lysyl-prolyl-arginine-paranitroanilide diacetate salt] 1298:1388 Following incubation with Protac (a specific activator of protein C), the heavy chain showed a slight decrease in molecular size and amidolytic activity measured by a synthetic chromogenic substrate containing an amide bond [H-D-(γ-carbobenzoxyl)-lysyl-prolyl-arginine-paranitroanilide diacetate salt]. 25326145 8 57 theme purified 1507:1514 arg1 protein 1516:1522 The purified protein 1503:1522 The purified protein 1503:1522 The purified protein showed concentration-dependent anti-factor V and anti-factor VIII activities in canine plasma in coagulometric factor assays. 25326145 3 58 gly glycosylated 527:538 arg1 kDa 610:612 ~ 25 kDa 605:612 ~ 25 kDa 605:612 RESULTS: The purified protein contained three glycosylated forms of a heavy chain (~49 kDa) and a glycosylated light chain (~ 25 kDa). 25326145 3 58 gly glycosylated 527:538 arg1 chain 557:561 a heavy chain 549:561 a heavy chain (~49 kDa) 549:571 RESULTS: The purified protein contained three glycosylated forms of a heavy chain (~49 kDa) and a glycosylated light chain (~ 25 kDa). 25326145 3 58 gly glycosylated 527:538 arg1 kDa 568:570 ~49 kDa 564:570 ~49 kDa 564:570 RESULTS: The purified protein contained three glycosylated forms of a heavy chain (~49 kDa) and a glycosylated light chain (~ 25 kDa). 25326145 3 58 gly glycosylated 527:538 arg1 chain 598:602 a glycosylated light chain 577:602 a glycosylated light chain (~ 25 kDa) 577:613 RESULTS: The purified protein contained three glycosylated forms of a heavy chain (~49 kDa) and a glycosylated light chain (~ 25 kDa). 25326145 3 58 gly glycosylated 527:538 arg1 forms 540:544 three glycosylated forms 521:544 three glycosylated forms of a heavy chain (~49 kDa) and a glycosylated light chain (~ 25 kDa) 521:613 RESULTS: The purified protein contained three glycosylated forms of a heavy chain (~49 kDa) and a glycosylated light chain (~ 25 kDa). 25326145 5 59 gly glycosylation 952:964 arg2 sequon 976:981 an N-linked glycosylation consensus sequon 940:981 an N-linked glycosylation consensus sequon 940:981 Three glycosylation sites (Asn139, Asn202, and Asn350) were identified by detection of peptides containing an N-linked glycosylation consensus sequon with a 3-dalton increase in mass following incubation of the protein with PNGase F in 18O-labeled water. 25326145 2 60 theme protein 226:232 arg1 C 234:234 protein C 226:234 protein C 226:234 The goals of this study were (1) to purify protein C from fresh frozen canine plasma by barium chloride and ammonium sulphate precipitation, followed by immunoaffinity chromatography using a monoclonal mouse antibody against human protein C (HPC4) and (2) to characterize this protein's structure. 25326145 8 61 theme coagulometric 1621:1633 arg1 assays 1642:1647 coagulometric factor assays 1621:1647 coagulometric factor assays 1621:1647 The purified protein showed concentration-dependent anti-factor V and anti-factor VIII activities in canine plasma in coagulometric factor assays. 25326145 5 62 theme peptides 920:927 arg1 detection 907:915 detection 907:915 detection of peptides containing an N-linked glycosylation consensus sequon with a 3-dalton increase in mass following incubation of the protein with PNGase F in 18O-labeled water 907:1085 Three glycosylation sites (Asn139, Asn202, and Asn350) were identified by detection of peptides containing an N-linked glycosylation consensus sequon with a 3-dalton increase in mass following incubation of the protein with PNGase F in 18O-labeled water. 25326145 3 63 theme purified 494:501 arg1 protein 503:509 The purified protein 490:509 The purified protein 490:509 RESULTS: The purified protein contained three glycosylated forms of a heavy chain (~49 kDa) and a glycosylated light chain (~ 25 kDa). 25326145 8 64 theme concentration-dependent 1531:1553 arg1 V 1567:1567 concentration-dependent anti-factor V 1531:1567 concentration-dependent anti-factor V 1531:1567 The purified protein showed concentration-dependent anti-factor V and anti-factor VIII activities in canine plasma in coagulometric factor assays. 25326145 4 65 theme vitamin 756:762 arg1 C 784:784 vitamin K-dependent protein C 756:784 vitamin K-dependent protein C precursor 756:794 |Tandem mass spectra of the peptides obtained following trypsin digestion and liquid chromatography identified this protein to be protein C (vitamin K-dependent protein C precursor, gi||62078422) with 100% probability.| 25326145 5 66 dep sites 853:857 arg1 Asn202 868:873 Asn202 868:873 Asn202 868:873 Three glycosylation sites (Asn139, Asn202, and Asn350) were identified by detection of peptides containing an N-linked glycosylation consensus sequon with a 3-dalton increase in mass following incubation of the protein with PNGase F in 18O-labeled water. 25326145 5 66 dep sites 853:857 arg1 Asn350 880:885 Asn350 880:885 Asn350 880:885 Three glycosylation sites (Asn139, Asn202, and Asn350) were identified by detection of peptides containing an N-linked glycosylation consensus sequon with a 3-dalton increase in mass following incubation of the protein with PNGase F in 18O-labeled water. 25326145 5 66 dep sites 853:857 arg1 Asn139 860:865 Asn139 860:865 Asn139 860:865 Three glycosylation sites (Asn139, Asn202, and Asn350) were identified by detection of peptides containing an N-linked glycosylation consensus sequon with a 3-dalton increase in mass following incubation of the protein with PNGase F in 18O-labeled water. 25326145 5 66 dep sites 853:857 arg1 sites 853:857 Three glycosylation sites 833:857 Three glycosylation sites (Asn139, Asn202, and Asn350) 833:886 Three glycosylation sites (Asn139, Asn202, and Asn350) were identified by detection of peptides containing an N-linked glycosylation consensus sequon with a 3-dalton increase in mass following incubation of the protein with PNGase F in 18O-labeled water. 25326145 3 67 theme glycosylated 527:538 arg1 forms 540:544 three glycosylated forms 521:544 three glycosylated forms of a heavy chain (~49 kDa) and a glycosylated light chain (~ 25 kDa) 521:613 RESULTS: The purified protein contained three glycosylated forms of a heavy chain (~49 kDa) and a glycosylated light chain (~ 25 kDa). 25326145 1 68 theme canine 112:117 arg1 CnPC 130:133 CnPC 130:133 CnPC 130:133 BACKGROUND: In order to characterize the functional properties of canine protein C (CnPC), the zymogen needs to be purified from plasma. 25326145 1 68 theme canine 112:117 arg1 C 127:127 canine protein C 112:127 canine protein C (CnPC) 112:134 BACKGROUND: In order to characterize the functional properties of canine protein C (CnPC), the zymogen needs to be purified from plasma. 25326145 4 69 with C 753:753 arg1 probability 820:830 100% probability 815:830 100% probability 815:830 |Tandem mass spectra of the peptides obtained following trypsin digestion and liquid chromatography identified this protein to be protein C (vitamin K-dependent protein C precursor, gi||62078422) with 100% probability.| 25326145 4 70 theme protein 776:782 arg1 C 784:784 vitamin K-dependent protein C 756:784 vitamin K-dependent protein C precursor 756:794 |Tandem mass spectra of the peptides obtained following trypsin digestion and liquid chromatography identified this protein to be protein C (vitamin K-dependent protein C precursor, gi||62078422) with 100% probability.| 25326145 1 71 theme C 127:127 arg1 properties 98:107 the functional properties 83:107 the functional properties of canine protein C (CnPC) 83:134 BACKGROUND: In order to characterize the functional properties of canine protein C (CnPC), the zymogen needs to be purified from plasma. 25326145 6 72 with incubation 1098:1107 arg1 Protac 1114:1119 Protac 1114:1119 Protac (a specific activator of protein C) 1114:1155 Following incubation with Protac (a specific activator of protein C), the heavy chain showed a slight decrease in molecular size and amidolytic activity measured by a synthetic chromogenic substrate containing an amide bond [H-D-(γ-carbobenzoxyl)-lysyl-prolyl-arginine-paranitroanilide diacetate salt]. 25326145 6 73 from decrease 1190:1197 arg1 size 1212:1215 molecular size 1202:1215 molecular size 1202:1215 Following incubation with Protac (a specific activator of protein C), the heavy chain showed a slight decrease in molecular size and amidolytic activity measured by a synthetic chromogenic substrate containing an amide bond [H-D-(γ-carbobenzoxyl)-lysyl-prolyl-arginine-paranitroanilide diacetate salt]. 25326145 6 73 from decrease 1190:1197 arg1 activity 1232:1239 amidolytic activity 1221:1239 amidolytic activity 1221:1239 Following incubation with Protac (a specific activator of protein C), the heavy chain showed a slight decrease in molecular size and amidolytic activity measured by a synthetic chromogenic substrate containing an amide bond [H-D-(γ-carbobenzoxyl)-lysyl-prolyl-arginine-paranitroanilide diacetate salt]. 25326145 5 74 gly glycosylation 839:851 arg2 sites 853:857 Three glycosylation sites 833:857 Three glycosylation sites (Asn139, Asn202, and Asn350) 833:886 Three glycosylation sites (Asn139, Asn202, and Asn350) were identified by detection of peptides containing an N-linked glycosylation consensus sequon with a 3-dalton increase in mass following incubation of the protein with PNGase F in 18O-labeled water. 25326145 5 74 gly glycosylation 839:851 arg2 Three 833:837 Three 833:837 Three 833:837 Three glycosylation sites (Asn139, Asn202, and Asn350) were identified by detection of peptides containing an N-linked glycosylation consensus sequon with a 3-dalton increase in mass following incubation of the protein with PNGase F in 18O-labeled water. 25326145 5 74 gly glycosylation 839:851 arg2 Asn350 880:885 Asn350 880:885 Asn350 880:885 Three glycosylation sites (Asn139, Asn202, and Asn350) were identified by detection of peptides containing an N-linked glycosylation consensus sequon with a 3-dalton increase in mass following incubation of the protein with PNGase F in 18O-labeled water. 25326145 5 74 gly glycosylation 839:851 arg2 Asn202 868:873 Asn202 868:873 Asn202 868:873 Three glycosylation sites (Asn139, Asn202, and Asn350) were identified by detection of peptides containing an N-linked glycosylation consensus sequon with a 3-dalton increase in mass following incubation of the protein with PNGase F in 18O-labeled water. 25326145 5 74 gly glycosylation 839:851 arg2 Asn139 860:865 Asn139 860:865 Asn139 860:865 Three glycosylation sites (Asn139, Asn202, and Asn350) were identified by detection of peptides containing an N-linked glycosylation consensus sequon with a 3-dalton increase in mass following incubation of the protein with PNGase F in 18O-labeled water. 25326145 1 75 dep characterize 70:81 arg1 to 67:68 to 67:68 to 67:68 BACKGROUND: In order to characterize the functional properties of canine protein C (CnPC), the zymogen needs to be purified from plasma. 25326145 6 76 theme molecular 1202:1210 arg1 size 1212:1215 molecular size 1202:1215 molecular size 1202:1215 Following incubation with Protac (a specific activator of protein C), the heavy chain showed a slight decrease in molecular size and amidolytic activity measured by a synthetic chromogenic substrate containing an amide bond [H-D-(γ-carbobenzoxyl)-lysyl-prolyl-arginine-paranitroanilide diacetate salt]. 25326145 4 77 theme mass 623:626 arg1 spectra 628:634 Tandem mass spectra 616:634 Tandem mass spectra of the peptides obtained following trypsin digestion and liquid chromatography 616:713 |Tandem mass spectra of the peptides obtained following trypsin digestion and liquid chromatography identified this protein to be protein C (vitamin K-dependent protein C precursor, gi||62078422) with 100% probability.| 25326145 5 78 theme glycosylation 952:964 arg1 sequon 976:981 an N-linked glycosylation consensus sequon 940:981 an N-linked glycosylation consensus sequon 940:981 Three glycosylation sites (Asn139, Asn202, and Asn350) were identified by detection of peptides containing an N-linked glycosylation consensus sequon with a 3-dalton increase in mass following incubation of the protein with PNGase F in 18O-labeled water. 25326145 5 79 theme glycosylation 839:851 arg1 Asn202 868:873 Asn202 868:873 Asn202 868:873 Three glycosylation sites (Asn139, Asn202, and Asn350) were identified by detection of peptides containing an N-linked glycosylation consensus sequon with a 3-dalton increase in mass following incubation of the protein with PNGase F in 18O-labeled water. 25326145 5 79 theme glycosylation 839:851 arg1 Asn350 880:885 Asn350 880:885 Asn350 880:885 Three glycosylation sites (Asn139, Asn202, and Asn350) were identified by detection of peptides containing an N-linked glycosylation consensus sequon with a 3-dalton increase in mass following incubation of the protein with PNGase F in 18O-labeled water. 25326145 5 79 theme glycosylation 839:851 arg1 Asn139 860:865 Asn139 860:865 Asn139 860:865 Three glycosylation sites (Asn139, Asn202, and Asn350) were identified by detection of peptides containing an N-linked glycosylation consensus sequon with a 3-dalton increase in mass following incubation of the protein with PNGase F in 18O-labeled water. 25326145 5 79 theme glycosylation 839:851 arg1 sites 853:857 Three glycosylation sites 833:857 Three glycosylation sites (Asn139, Asn202, and Asn350) 833:886 Three glycosylation sites (Asn139, Asn202, and Asn350) were identified by detection of peptides containing an N-linked glycosylation consensus sequon with a 3-dalton increase in mass following incubation of the protein with PNGase F in 18O-labeled water. 25326145 4 80 theme % 818:818 arg1 probability 820:830 100% probability 815:830 100% probability 815:830 |Tandem mass spectra of the peptides obtained following trypsin digestion and liquid chromatography identified this protein to be protein C (vitamin K-dependent protein C precursor, gi||62078422) with 100% probability.| 25326145 2 81 theme monoclonal 374:383 arg1 antibody 391:398 a monoclonal mouse antibody 372:398 a monoclonal mouse antibody against human protein C 372:422 The goals of this study were (1) to purify protein C from fresh frozen canine plasma by barium chloride and ammonium sulphate precipitation, followed by immunoaffinity chromatography using a monoclonal mouse antibody against human protein C (HPC4) and (2) to characterize this protein's structure. 25326145 2 82 theme ammonium 291:298 arg1 precipitation 309:321 ammonium sulphate precipitation 291:321 ammonium sulphate precipitation 291:321 The goals of this study were (1) to purify protein C from fresh frozen canine plasma by barium chloride and ammonium sulphate precipitation, followed by immunoaffinity chromatography using a monoclonal mouse antibody against human protein C (HPC4) and (2) to characterize this protein's structure. 25326145 0 83 theme C 24:24 arg1 Purification 0:11 Purification 0:11 Purification of protein C from canine plasma. 0:44 Purification of protein C from canine plasma. 25326145 3 84 theme heavy 551:555 arg1 chain 557:561 a heavy chain 549:561 a heavy chain (~49 kDa) 549:571 RESULTS: The purified protein contained three glycosylated forms of a heavy chain (~49 kDa) and a glycosylated light chain (~ 25 kDa). 25326145 3 84 theme heavy 551:555 arg1 kDa 568:570 ~49 kDa 564:570 ~49 kDa 564:570 RESULTS: The purified protein contained three glycosylated forms of a heavy chain (~49 kDa) and a glycosylated light chain (~ 25 kDa). 25326145 2 85 theme immunoaffinity 336:349 arg1 chromatography 351:364 immunoaffinity chromatography 336:364 immunoaffinity chromatography using a monoclonal mouse antibody against human protein C 336:422 The goals of this study were (1) to purify protein C from fresh frozen canine plasma by barium chloride and ammonium sulphate precipitation, followed by immunoaffinity chromatography using a monoclonal mouse antibody against human protein C (HPC4) and (2) to characterize this protein's structure. 25326145 6 86 theme synthetic 1255:1263 arg1 substrate 1277:1285 a synthetic chromogenic substrate 1253:1285 a synthetic chromogenic substrate containing an amide bond [H-D-(γ-carbobenzoxyl)-lysyl-prolyl-arginine-paranitroanilide diacetate salt] 1253:1388 Following incubation with Protac (a specific activator of protein C), the heavy chain showed a slight decrease in molecular size and amidolytic activity measured by a synthetic chromogenic substrate containing an amide bond [H-D-(γ-carbobenzoxyl)-lysyl-prolyl-arginine-paranitroanilide diacetate salt]. 25326145 8 87 theme anti-factor 1555:1565 arg1 V 1567:1567 concentration-dependent anti-factor V 1531:1567 concentration-dependent anti-factor V 1531:1567 The purified protein showed concentration-dependent anti-factor V and anti-factor VIII activities in canine plasma in coagulometric factor assays. 25326145 2 88 theme human 408:412 arg1 C 422:422 human protein C 408:422 human protein C 408:422 The goals of this study were (1) to purify protein C from fresh frozen canine plasma by barium chloride and ammonium sulphate precipitation, followed by immunoaffinity chromatography using a monoclonal mouse antibody against human protein C (HPC4) and (2) to characterize this protein's structure. 25326145 2 89 dep followed 324:331 arg1 HPC4 425:428 HPC4 425:428 HPC4 425:428 The goals of this study were (1) to purify protein C from fresh frozen canine plasma by barium chloride and ammonium sulphate precipitation, followed by immunoaffinity chromatography using a monoclonal mouse antibody against human protein C (HPC4) and (2) to characterize this protein's structure. 25326145 6 90 theme heavy 1162:1166 arg1 chain 1168:1172 the heavy chain 1158:1172 the heavy chain 1158:1172 Following incubation with Protac (a specific activator of protein C), the heavy chain showed a slight decrease in molecular size and amidolytic activity measured by a synthetic chromogenic substrate containing an amide bond [H-D-(γ-carbobenzoxyl)-lysyl-prolyl-arginine-paranitroanilide diacetate salt]. 25326145 4 91 theme liquid 693:698 arg1 chromatography 700:713 liquid chromatography 693:713 liquid chromatography 693:713 |Tandem mass spectra of the peptides obtained following trypsin digestion and liquid chromatography identified this protein to be protein C (vitamin K-dependent protein C precursor, gi||62078422) with 100% probability.| 25326145 2 92 theme canine 254:259 arg1 plasma 261:266 fresh frozen canine plasma 241:266 fresh frozen canine plasma 241:266 The goals of this study were (1) to purify protein C from fresh frozen canine plasma by barium chloride and ammonium sulphate precipitation, followed by immunoaffinity chromatography using a monoclonal mouse antibody against human protein C (HPC4) and (2) to characterize this protein's structure. 25326145 6 93 theme diacetate 1374:1382 arg1 salt 1384:1387 an amide bond [H-D-(γ-carbobenzoxyl)-lysyl-prolyl-arginine-paranitroanilide diacetate salt] 1298:1388 an amide bond [H-D-(γ-carbobenzoxyl)-lysyl-prolyl-arginine-paranitroanilide diacetate salt] 1298:1388 Following incubation with Protac (a specific activator of protein C), the heavy chain showed a slight decrease in molecular size and amidolytic activity measured by a synthetic chromogenic substrate containing an amide bond [H-D-(γ-carbobenzoxyl)-lysyl-prolyl-arginine-paranitroanilide diacetate salt]. 25326145 9 94 with activation 1810:1819 arg1 Protac 1826:1831 Protac 1826:1831 Protac 1826:1831 CONCLUSIONS: These studies showed that CnPC could be purified from plasma using HPC4 and that this protein showed amidolytic and anti-coagulant properties upon activation with Protac. 25326145 4 95 theme peptides 643:650 arg1 spectra 628:634 Tandem mass spectra 616:634 Tandem mass spectra of the peptides obtained following trypsin digestion and liquid chromatography 616:713 |Tandem mass spectra of the peptides obtained following trypsin digestion and liquid chromatography identified this protein to be protein C (vitamin K-dependent protein C precursor, gi||62078422) with 100% probability.| 25326145 2 96 theme fresh 241:245 arg1 plasma 261:266 fresh frozen canine plasma 241:266 fresh frozen canine plasma 241:266 The goals of this study were (1) to purify protein C from fresh frozen canine plasma by barium chloride and ammonium sulphate precipitation, followed by immunoaffinity chromatography using a monoclonal mouse antibody against human protein C (HPC4) and (2) to characterize this protein's structure. 25326145 8 97 theme V 1567:1567 arg1 activities 1590:1599 concentration-dependent anti-factor V and anti-factor VIII activities 1531:1599 concentration-dependent anti-factor V and anti-factor VIII activities in canine plasma 1531:1616 The purified protein showed concentration-dependent anti-factor V and anti-factor VIII activities in canine plasma in coagulometric factor assays. 25326145 6 98 dep Protac 1114:1119 arg1 activator 1133:1141 a specific activator 1122:1141 a specific activator of protein C 1122:1154 Following incubation with Protac (a specific activator of protein C), the heavy chain showed a slight decrease in molecular size and amidolytic activity measured by a synthetic chromogenic substrate containing an amide bond [H-D-(γ-carbobenzoxyl)-lysyl-prolyl-arginine-paranitroanilide diacetate salt]. 25326145 9 99 theme amidolytic 1764:1773 arg1 properties 1794:1803 amidolytic and anti-coagulant properties 1764:1803 amidolytic and anti-coagulant properties 1764:1803 CONCLUSIONS: These studies showed that CnPC could be purified from plasma using HPC4 and that this protein showed amidolytic and anti-coagulant properties upon activation with Protac. 25326145 3 100 theme glycosylated 579:590 arg1 kDa 610:612 ~ 25 kDa 605:612 ~ 25 kDa 605:612 RESULTS: The purified protein contained three glycosylated forms of a heavy chain (~49 kDa) and a glycosylated light chain (~ 25 kDa). 25326145 3 100 theme glycosylated 579:590 arg1 chain 598:602 a glycosylated light chain 577:602 a glycosylated light chain (~ 25 kDa) 577:613 RESULTS: The purified protein contained three glycosylated forms of a heavy chain (~49 kDa) and a glycosylated light chain (~ 25 kDa). 25326145 8 101 theme anti-factor 1573:1583 arg1 VIII 1585:1588 anti-factor VIII 1573:1588 anti-factor VIII 1573:1588 The purified protein showed concentration-dependent anti-factor V and anti-factor VIII activities in canine plasma in coagulometric factor assays. 27582497 10 0 theme predicted 1404:1412 arg1 residues 1427:1434 predicted zinc-binding residues 1404:1434 predicted zinc-binding residues 1404:1434 Recombinant LITAF contains 1 mol/mol zinc, while mutation of predicted zinc-binding residues disrupts LITAF membrane association. 27582497 3 1 theme zinc 525:528 arg1 fingers 530:536 zinc fingers 525:536 zinc fingers 525:536 These mutations map to a highly conserved C-terminal region, termed the LITAF domain, which includes a 22 residue hydrophobic sequence and flanking cysteine-rich regions that contain peptide motifs found in zinc fingers. 27582497 2 2 theme type 309:312 arg1 1C 314:315 autosomal-dominant Charcot Marie Tooth disease type 1C 262:315 autosomal-dominant Charcot Marie Tooth disease type 1C 262:315 Several mutations in LITAF cause autosomal-dominant Charcot Marie Tooth disease type 1C. 27582497 12 3 theme LITAF 1767:1771 arg1 proteins 1780:1787 LITAF family proteins 1767:1787 LITAF family proteins 1767:1787 The related human protein, CDIP1 (cell death involved p53 target 1), displays identical membrane topology, suggesting that this mode of membrane integration is conserved in LITAF family proteins. 27582497 10 4 theme LITAF 1445:1449 arg1 association 1460:1470 LITAF membrane association 1445:1470 LITAF membrane association 1445:1470 Recombinant LITAF contains 1 mol/mol zinc, while mutation of predicted zinc-binding residues disrupts LITAF membrane association. 27582497 2 5 theme Tooth 295:299 arg1 1C 314:315 autosomal-dominant Charcot Marie Tooth disease type 1C 262:315 autosomal-dominant Charcot Marie Tooth disease type 1C 262:315 Several mutations in LITAF cause autosomal-dominant Charcot Marie Tooth disease type 1C. 27582497 8 6 from protein 1197:1203 arg1 cells 1208:1212 cells 1208:1212 cells 1208:1212 Expression in cells of an LITAF construct containing C-terminal glycosylation sites confirms that LITAF is not a TA protein in cells. 27582497 10 7 theme residues 1427:1434 arg1 mutation 1392:1399 mutation 1392:1399 mutation of predicted zinc-binding residues 1392:1434 Recombinant LITAF contains 1 mol/mol zinc, while mutation of predicted zinc-binding residues disrupts LITAF membrane association. 27582497 12 8 theme integration 1739:1749 arg1 mode 1722:1725 this mode 1717:1725 this mode of membrane integration 1717:1749 The related human protein, CDIP1 (cell death involved p53 target 1), displays identical membrane topology, suggesting that this mode of membrane integration is conserved in LITAF family proteins. 27582497 4 9 theme LITAF 645:649 arg1 topology 633:640 the membrane topology 620:640 the membrane topology of LITAF 620:649 Although the LITAF domain is thought to be responsible for membrane integration, the membrane topology of LITAF has not been established. 27582497 9 10 theme immunofluorescence-based 1227:1250 arg1 assay 1260:1264 an immunofluorescence-based latency assay 1224:1264 an immunofluorescence-based latency assay 1224:1264 Finally, an immunofluorescence-based latency assay showed that both the N- and C-termini of LITAF are exposed to the cytoplasm. 27582497 1 11 theme body 215:218 arg1 sorting 220:226 multivesicular body sorting 200:226 multivesicular body sorting 200:226 LITAF (LPS-induced TNF-activating factor) is an endosome-associated integral membrane protein important for multivesicular body sorting. 27582497 2 12 theme Several 229:235 arg1 mutations 237:245 Several mutations 229:245 Several mutations in LITAF 229:254 Several mutations in LITAF cause autosomal-dominant Charcot Marie Tooth disease type 1C. 27582497 1 13 theme TNF-activating 111:124 arg1 factor 126:131 LPS-induced TNF-activating factor 99:131 LPS-induced TNF-activating factor 99:131 LITAF (LPS-induced TNF-activating factor) is an endosome-associated integral membrane protein important for multivesicular body sorting. 27582497 1 13 theme TNF-activating 111:124 arg1 LITAF 92:96 LITAF 92:96 LITAF (LPS-induced TNF-activating factor) 92:132 LITAF (LPS-induced TNF-activating factor) is an endosome-associated integral membrane protein important for multivesicular body sorting. 27582497 12 14 theme human 1606:1610 arg1 CDIP1 1621:1625 CDIP1 1621:1625 CDIP1 (cell death involved p53 target 1) 1621:1660 The related human protein, CDIP1 (cell death involved p53 target 1), displays identical membrane topology, suggesting that this mode of membrane integration is conserved in LITAF family proteins. 27582497 12 14 theme human 1606:1610 arg1 protein 1612:1618 The related human protein 1594:1618 The related human protein 1594:1618 The related human protein, CDIP1 (cell death involved p53 target 1), displays identical membrane topology, suggesting that this mode of membrane integration is conserved in LITAF family proteins. 27582497 5 15 dep tail-anchored 723:735 arg1 TA 738:739 TA 738:739 TA 738:739 Here, we have investigated whether LITAF is a tail-anchored (TA) membrane-spanning protein or monotopic membrane protein. 27582497 11 16 theme monotopic 1508:1516 arg1 protein 1527:1533 a monotopic membrane protein 1506:1533 a monotopic membrane protein whose membrane integration is stabilised by a zinc finger 1506:1591 Hence, we conclude that LITAF is a monotopic membrane protein whose membrane integration is stabilised by a zinc finger. 27582497 11 16 theme monotopic 1508:1516 arg1 LITAF 1497:1501 LITAF 1497:1501 LITAF 1497:1501 Hence, we conclude that LITAF is a monotopic membrane protein whose membrane integration is stabilised by a zinc finger. 27582497 3 17 located found 516:520 arg1 fingers 530:536 zinc fingers 525:536 zinc fingers 525:536 These mutations map to a highly conserved C-terminal region, termed the LITAF domain, which includes a 22 residue hydrophobic sequence and flanking cysteine-rich regions that contain peptide motifs found in zinc fingers. 27582497 3 17 located found 516:520 arg2 motifs 509:514 peptide motifs 501:514 peptide motifs found in zinc fingers 501:536 These mutations map to a highly conserved C-terminal region, termed the LITAF domain, which includes a 22 residue hydrophobic sequence and flanking cysteine-rich regions that contain peptide motifs found in zinc fingers. 27582497 12 18 theme membrane 1682:1689 arg1 topology 1691:1698 identical membrane topology 1672:1698 identical membrane topology 1672:1698 The related human protein, CDIP1 (cell death involved p53 target 1), displays identical membrane topology, suggesting that this mode of membrane integration is conserved in LITAF family proteins. 27582497 11 19 theme membrane 1541:1548 arg1 integration 1550:1560 integration 1550:1560 integration 1550:1560 Hence, we conclude that LITAF is a monotopic membrane protein whose membrane integration is stabilised by a zinc finger. 27582497 7 20 link N-linked 951:958 arg1 reporters 974:982 N-linked glycosylation reporters 951:982 N-linked glycosylation reporters 951:982 Furthermore, introduction of N-linked glycosylation reporters shows that neither the N-terminal nor C-terminal domains of LITAF translocate into the ER lumen. 27582497 0 21 theme monotopic 64:72 arg1 LITAF 40:44 The Charcot Marie Tooth disease protein LITAF 0:44 The Charcot Marie Tooth disease protein LITAF 0:44 The Charcot Marie Tooth disease protein LITAF is a zinc-binding monotopic membrane protein. 27582497 0 21 theme monotopic 64:72 arg1 protein 83:89 a zinc-binding monotopic membrane protein 49:89 a zinc-binding monotopic membrane protein 49:89 The Charcot Marie Tooth disease protein LITAF is a zinc-binding monotopic membrane protein. 27582497 7 22 theme reporters 974:982 arg1 introduction 935:946 introduction 935:946 introduction of N-linked glycosylation reporters 935:982 Furthermore, introduction of N-linked glycosylation reporters shows that neither the N-terminal nor C-terminal domains of LITAF translocate into the ER lumen. 27582497 1 23 theme integral 160:167 arg1 LITAF 92:96 LITAF 92:96 LITAF (LPS-induced TNF-activating factor) 92:132 LITAF (LPS-induced TNF-activating factor) is an endosome-associated integral membrane protein important for multivesicular body sorting. 27582497 1 23 theme integral 160:167 arg1 protein 178:184 an endosome-associated integral membrane protein 137:184 an endosome-associated integral membrane protein important for multivesicular body sorting 137:226 LITAF (LPS-induced TNF-activating factor) is an endosome-associated integral membrane protein important for multivesicular body sorting. 27582497 7 24 theme N-linked 951:958 arg1 reporters 974:982 N-linked glycosylation reporters 951:982 N-linked glycosylation reporters 951:982 Furthermore, introduction of N-linked glycosylation reporters shows that neither the N-terminal nor C-terminal domains of LITAF translocate into the ER lumen. 27582497 2 25 from mutations 237:245 arg1 LITAF 250:254 LITAF 250:254 LITAF 250:254 Several mutations in LITAF cause autosomal-dominant Charcot Marie Tooth disease type 1C. 27582497 3 26 theme C-terminal 360:369 arg1 region 371:376 a highly conserved C-terminal region 341:376 a highly conserved C-terminal region 341:376 These mutations map to a highly conserved C-terminal region, termed the LITAF domain, which includes a 22 residue hydrophobic sequence and flanking cysteine-rich regions that contain peptide motifs found in zinc fingers. 27582497 3 27 contain contain 493:499 arg1 sequence 444:451 a 22 residue hydrophobic sequence 419:451 a 22 residue hydrophobic sequence 419:451 These mutations map to a highly conserved C-terminal region, termed the LITAF domain, which includes a 22 residue hydrophobic sequence and flanking cysteine-rich regions that contain peptide motifs found in zinc fingers. 27582497 3 27 contain contain 493:499 arg1 regions 480:486 flanking cysteine-rich regions 457:486 flanking cysteine-rich regions 457:486 These mutations map to a highly conserved C-terminal region, termed the LITAF domain, which includes a 22 residue hydrophobic sequence and flanking cysteine-rich regions that contain peptide motifs found in zinc fingers. 27582497 3 27 contain contain 493:499 arg2 motifs 509:514 peptide motifs 501:514 peptide motifs found in zinc fingers 501:536 These mutations map to a highly conserved C-terminal region, termed the LITAF domain, which includes a 22 residue hydrophobic sequence and flanking cysteine-rich regions that contain peptide motifs found in zinc fingers. 27582497 0 28 theme protein 32:38 arg1 LITAF 40:44 The Charcot Marie Tooth disease protein LITAF 0:44 The Charcot Marie Tooth disease protein LITAF 0:44 The Charcot Marie Tooth disease protein LITAF is a zinc-binding monotopic membrane protein. 27582497 0 28 theme protein 32:38 arg1 protein 83:89 a zinc-binding monotopic membrane protein 49:89 a zinc-binding monotopic membrane protein 49:89 The Charcot Marie Tooth disease protein LITAF is a zinc-binding monotopic membrane protein. 27582497 0 29 theme zinc-binding 51:62 arg1 LITAF 40:44 The Charcot Marie Tooth disease protein LITAF 0:44 The Charcot Marie Tooth disease protein LITAF 0:44 The Charcot Marie Tooth disease protein LITAF is a zinc-binding monotopic membrane protein. 27582497 0 29 theme zinc-binding 51:62 arg1 protein 83:89 a zinc-binding monotopic membrane protein 49:89 a zinc-binding monotopic membrane protein 49:89 The Charcot Marie Tooth disease protein LITAF is a zinc-binding monotopic membrane protein. 27582497 3 30 theme residue 424:430 arg1 sequence 444:451 a 22 residue hydrophobic sequence 419:451 a 22 residue hydrophobic sequence 419:451 These mutations map to a highly conserved C-terminal region, termed the LITAF domain, which includes a 22 residue hydrophobic sequence and flanking cysteine-rich regions that contain peptide motifs found in zinc fingers. 27582497 12 31 theme involved 1639:1646 arg1 CDIP1 1621:1625 CDIP1 1621:1625 CDIP1 (cell death involved p53 target 1) 1621:1660 The related human protein, CDIP1 (cell death involved p53 target 1), displays identical membrane topology, suggesting that this mode of membrane integration is conserved in LITAF family proteins. 27582497 12 31 theme involved 1639:1646 arg1 target 1652:1657 cell death involved p53 target 1 1628:1659 cell death involved p53 target 1 1628:1659 The related human protein, CDIP1 (cell death involved p53 target 1), displays identical membrane topology, suggesting that this mode of membrane integration is conserved in LITAF family proteins. 27582497 0 32 theme Marie 12:16 arg1 LITAF 40:44 The Charcot Marie Tooth disease protein LITAF 0:44 The Charcot Marie Tooth disease protein LITAF 0:44 The Charcot Marie Tooth disease protein LITAF is a zinc-binding monotopic membrane protein. 27582497 0 32 theme Marie 12:16 arg1 protein 83:89 a zinc-binding monotopic membrane protein 49:89 a zinc-binding monotopic membrane protein 49:89 The Charcot Marie Tooth disease protein LITAF is a zinc-binding monotopic membrane protein. 27582497 3 33 theme flanking 457:464 arg1 regions 480:486 flanking cysteine-rich regions 457:486 flanking cysteine-rich regions 457:486 These mutations map to a highly conserved C-terminal region, termed the LITAF domain, which includes a 22 residue hydrophobic sequence and flanking cysteine-rich regions that contain peptide motifs found in zinc fingers. 27582497 0 34 theme disease 24:30 arg1 LITAF 40:44 The Charcot Marie Tooth disease protein LITAF 0:44 The Charcot Marie Tooth disease protein LITAF 0:44 The Charcot Marie Tooth disease protein LITAF is a zinc-binding monotopic membrane protein. 27582497 0 34 theme disease 24:30 arg1 protein 83:89 a zinc-binding monotopic membrane protein 49:89 a zinc-binding monotopic membrane protein 49:89 The Charcot Marie Tooth disease protein LITAF is a zinc-binding monotopic membrane protein. 27582497 10 35 contain contains 1361:1368 arg2 zinc 1380:1383 1 mol/mol zinc 1370:1383 1 mol/mol zinc 1370:1383 Recombinant LITAF contains 1 mol/mol zinc, while mutation of predicted zinc-binding residues disrupts LITAF membrane association. 27582497 10 35 contain contains 1361:1368 arg1 LITAF 1355:1359 Recombinant LITAF 1343:1359 Recombinant LITAF 1343:1359 Recombinant LITAF contains 1 mol/mol zinc, while mutation of predicted zinc-binding residues disrupts LITAF membrane association. 27582497 10 36 theme Recombinant 1343:1353 arg1 LITAF 1355:1359 Recombinant LITAF 1343:1359 Recombinant LITAF 1343:1359 Recombinant LITAF contains 1 mol/mol zinc, while mutation of predicted zinc-binding residues disrupts LITAF membrane association. 27582497 8 37 contain containing 1123:1132 arg1 construct 1113:1121 an LITAF construct 1104:1121 an LITAF construct containing C-terminal glycosylation sites 1104:1163 Expression in cells of an LITAF construct containing C-terminal glycosylation sites confirms that LITAF is not a TA protein in cells. 27582497 8 37 contain containing 1123:1132 arg2 sites 1159:1163 C-terminal glycosylation sites 1134:1163 C-terminal glycosylation sites 1134:1163 Expression in cells of an LITAF construct containing C-terminal glycosylation sites confirms that LITAF is not a TA protein in cells. 27582497 8 38 theme LITAF 1107:1111 arg1 construct 1113:1121 an LITAF construct 1104:1121 an LITAF construct containing C-terminal glycosylation sites 1104:1163 Expression in cells of an LITAF construct containing C-terminal glycosylation sites confirms that LITAF is not a TA protein in cells. 27582497 4 39 theme LITAF 552:556 arg1 responsible 582:592 responsible 582:592 responsible 582:592 Although the LITAF domain is thought to be responsible for membrane integration, the membrane topology of LITAF has not been established. 27582497 4 39 theme LITAF 552:556 arg1 domain 558:563 the LITAF domain 548:563 the LITAF domain 548:563 Although the LITAF domain is thought to be responsible for membrane integration, the membrane topology of LITAF has not been established. 27582497 8 40 theme glycosylation 1145:1157 arg1 sites 1159:1163 C-terminal glycosylation sites 1134:1163 C-terminal glycosylation sites 1134:1163 Expression in cells of an LITAF construct containing C-terminal glycosylation sites confirms that LITAF is not a TA protein in cells. 27582497 4 41 theme membrane 624:631 arg1 topology 633:640 the membrane topology 620:640 the membrane topology of LITAF 620:649 Although the LITAF domain is thought to be responsible for membrane integration, the membrane topology of LITAF has not been established. 27582497 6 42 theme TA 910:911 arg1 Sec61β 890:895 Sec61β 890:895 Sec61β 890:895 When translated in vitro, LITAF integrates poorly into ER-derived microsomes compared with Sec61β, a bona fide TA protein. 27582497 6 42 theme TA 910:911 arg1 protein 913:919 a bona fide TA protein 898:919 a bona fide TA protein 898:919 When translated in vitro, LITAF integrates poorly into ER-derived microsomes compared with Sec61β, a bona fide TA protein. 27582497 6 43 theme bona 900:903 arg1 Sec61β 890:895 Sec61β 890:895 Sec61β 890:895 When translated in vitro, LITAF integrates poorly into ER-derived microsomes compared with Sec61β, a bona fide TA protein. 27582497 6 43 theme bona 900:903 arg1 protein 913:919 a bona fide TA protein 898:919 a bona fide TA protein 898:919 When translated in vitro, LITAF integrates poorly into ER-derived microsomes compared with Sec61β, a bona fide TA protein. 27582497 12 44 theme family 1773:1778 arg1 proteins 1780:1787 LITAF family proteins 1767:1787 LITAF family proteins 1767:1787 The related human protein, CDIP1 (cell death involved p53 target 1), displays identical membrane topology, suggesting that this mode of membrane integration is conserved in LITAF family proteins. 27582497 4 45 theme membrane 598:605 arg1 integration 607:617 membrane integration 598:617 membrane integration 598:617 Although the LITAF domain is thought to be responsible for membrane integration, the membrane topology of LITAF has not been established. 27582497 2 46 theme disease 301:307 arg1 1C 314:315 autosomal-dominant Charcot Marie Tooth disease type 1C 262:315 autosomal-dominant Charcot Marie Tooth disease type 1C 262:315 Several mutations in LITAF cause autosomal-dominant Charcot Marie Tooth disease type 1C. 27582497 1 47 theme membrane 169:176 arg1 LITAF 92:96 LITAF 92:96 LITAF (LPS-induced TNF-activating factor) 92:132 LITAF (LPS-induced TNF-activating factor) is an endosome-associated integral membrane protein important for multivesicular body sorting. 27582497 1 47 theme membrane 169:176 arg1 protein 178:184 an endosome-associated integral membrane protein 137:184 an endosome-associated integral membrane protein important for multivesicular body sorting 137:226 LITAF (LPS-induced TNF-activating factor) is an endosome-associated integral membrane protein important for multivesicular body sorting. 27582497 12 48 theme membrane 1730:1737 arg1 integration 1739:1749 membrane integration 1730:1749 membrane integration 1730:1749 The related human protein, CDIP1 (cell death involved p53 target 1), displays identical membrane topology, suggesting that this mode of membrane integration is conserved in LITAF family proteins. 27582497 5 49 theme monotopic 771:779 arg1 protein 790:796 monotopic membrane protein 771:796 monotopic membrane protein 771:796 Here, we have investigated whether LITAF is a tail-anchored (TA) membrane-spanning protein or monotopic membrane protein. 27582497 1 50 theme important 186:194 arg1 LITAF 92:96 LITAF 92:96 LITAF (LPS-induced TNF-activating factor) 92:132 LITAF (LPS-induced TNF-activating factor) is an endosome-associated integral membrane protein important for multivesicular body sorting. 27582497 1 50 theme important 186:194 arg1 protein 178:184 an endosome-associated integral membrane protein 137:184 an endosome-associated integral membrane protein important for multivesicular body sorting 137:226 LITAF (LPS-induced TNF-activating factor) is an endosome-associated integral membrane protein important for multivesicular body sorting. 27582497 8 51 theme TA 1194:1195 arg1 protein 1197:1203 a TA protein 1192:1203 a TA protein in cells 1192:1212 Expression in cells of an LITAF construct containing C-terminal glycosylation sites confirms that LITAF is not a TA protein in cells. 27582497 8 51 theme TA 1194:1195 arg1 LITAF 1179:1183 LITAF 1179:1183 LITAF 1179:1183 Expression in cells of an LITAF construct containing C-terminal glycosylation sites confirms that LITAF is not a TA protein in cells. 27582497 10 52 theme zinc-binding 1414:1425 arg1 residues 1427:1434 predicted zinc-binding residues 1404:1434 predicted zinc-binding residues 1404:1434 Recombinant LITAF contains 1 mol/mol zinc, while mutation of predicted zinc-binding residues disrupts LITAF membrane association. 27582497 1 53 theme multivesicular 200:213 arg1 sorting 220:226 multivesicular body sorting 200:226 multivesicular body sorting 200:226 LITAF (LPS-induced TNF-activating factor) is an endosome-associated integral membrane protein important for multivesicular body sorting. 27582497 12 54 theme cell 1628:1631 arg1 CDIP1 1621:1625 CDIP1 1621:1625 CDIP1 (cell death involved p53 target 1) 1621:1660 The related human protein, CDIP1 (cell death involved p53 target 1), displays identical membrane topology, suggesting that this mode of membrane integration is conserved in LITAF family proteins. 27582497 12 54 theme cell 1628:1631 arg1 target 1652:1657 cell death involved p53 target 1 1628:1659 cell death involved p53 target 1 1628:1659 The related human protein, CDIP1 (cell death involved p53 target 1), displays identical membrane topology, suggesting that this mode of membrane integration is conserved in LITAF family proteins. 27582497 7 55 theme ER 1071:1072 arg1 lumen 1074:1078 the ER lumen 1067:1078 the ER lumen 1067:1078 Furthermore, introduction of N-linked glycosylation reporters shows that neither the N-terminal nor C-terminal domains of LITAF translocate into the ER lumen. 27582497 9 56 theme latency 1252:1258 arg1 assay 1260:1264 an immunofluorescence-based latency assay 1224:1264 an immunofluorescence-based latency assay 1224:1264 Finally, an immunofluorescence-based latency assay showed that both the N- and C-termini of LITAF are exposed to the cytoplasm. 27582497 8 57 from Expression 1081:1090 arg1 cells 1095:1099 cells 1095:1099 cells of an LITAF construct containing C-terminal glycosylation sites 1095:1163 Expression in cells of an LITAF construct containing C-terminal glycosylation sites confirms that LITAF is not a TA protein in cells. 27582497 1 58 theme LPS-induced 99:109 arg1 factor 126:131 LPS-induced TNF-activating factor 99:131 LPS-induced TNF-activating factor 99:131 LITAF (LPS-induced TNF-activating factor) is an endosome-associated integral membrane protein important for multivesicular body sorting. 27582497 1 58 theme LPS-induced 99:109 arg1 LITAF 92:96 LITAF 92:96 LITAF (LPS-induced TNF-activating factor) 92:132 LITAF (LPS-induced TNF-activating factor) is an endosome-associated integral membrane protein important for multivesicular body sorting. 27582497 11 59 theme zinc 1581:1584 arg1 finger 1586:1591 a zinc finger 1579:1591 a zinc finger 1579:1591 Hence, we conclude that LITAF is a monotopic membrane protein whose membrane integration is stabilised by a zinc finger. 27582497 7 60 theme LITAF 1044:1048 arg1 LITAF 1044:1048 LITAF 1044:1048 LITAF 1044:1048 Furthermore, introduction of N-linked glycosylation reporters shows that neither the N-terminal nor C-terminal domains of LITAF translocate into the ER lumen. 27582497 7 60 theme LITAF 1044:1048 arg1 domains 1033:1039 neither the N-terminal nor C-terminal domains 995:1039 domains 1033:1039 Furthermore, introduction of N-linked glycosylation reporters shows that neither the N-terminal nor C-terminal domains of LITAF translocate into the ER lumen. 27582497 2 61 theme Marie 289:293 arg1 1C 314:315 autosomal-dominant Charcot Marie Tooth disease type 1C 262:315 autosomal-dominant Charcot Marie Tooth disease type 1C 262:315 Several mutations in LITAF cause autosomal-dominant Charcot Marie Tooth disease type 1C. 27582497 7 62 theme C-terminal 1022:1031 arg1 LITAF 1044:1048 LITAF 1044:1048 LITAF 1044:1048 Furthermore, introduction of N-linked glycosylation reporters shows that neither the N-terminal nor C-terminal domains of LITAF translocate into the ER lumen. 27582497 7 62 theme C-terminal 1022:1031 arg1 domains 1033:1039 neither the N-terminal nor C-terminal domains 995:1039 domains 1033:1039 Furthermore, introduction of N-linked glycosylation reporters shows that neither the N-terminal nor C-terminal domains of LITAF translocate into the ER lumen. 27582497 5 63 theme membrane-spanning 742:758 arg1 protein 760:766 a tail-anchored (TA) membrane-spanning protein 721:766 a tail-anchored (TA) membrane-spanning protein 721:766 Here, we have investigated whether LITAF is a tail-anchored (TA) membrane-spanning protein or monotopic membrane protein. 27582497 5 63 theme membrane-spanning 742:758 arg1 LITAF 712:716 LITAF 712:716 LITAF 712:716 Here, we have investigated whether LITAF is a tail-anchored (TA) membrane-spanning protein or monotopic membrane protein. 27582497 2 64 theme autosomal-dominant 262:279 arg1 1C 314:315 autosomal-dominant Charcot Marie Tooth disease type 1C 262:315 autosomal-dominant Charcot Marie Tooth disease type 1C 262:315 Several mutations in LITAF cause autosomal-dominant Charcot Marie Tooth disease type 1C. 27582497 7 65 theme N-terminal 1007:1016 arg1 LITAF 1044:1048 LITAF 1044:1048 LITAF 1044:1048 Furthermore, introduction of N-linked glycosylation reporters shows that neither the N-terminal nor C-terminal domains of LITAF translocate into the ER lumen. 27582497 7 65 theme N-terminal 1007:1016 arg1 domains 1033:1039 neither the N-terminal nor C-terminal domains 995:1039 domains 1033:1039 Furthermore, introduction of N-linked glycosylation reporters shows that neither the N-terminal nor C-terminal domains of LITAF translocate into the ER lumen. 27582497 3 66 theme conserved 350:358 arg1 region 371:376 a highly conserved C-terminal region 341:376 a highly conserved C-terminal region 341:376 These mutations map to a highly conserved C-terminal region, termed the LITAF domain, which includes a 22 residue hydrophobic sequence and flanking cysteine-rich regions that contain peptide motifs found in zinc fingers. 27582497 0 67 theme membrane 74:81 arg1 LITAF 40:44 The Charcot Marie Tooth disease protein LITAF 0:44 The Charcot Marie Tooth disease protein LITAF 0:44 The Charcot Marie Tooth disease protein LITAF is a zinc-binding monotopic membrane protein. 27582497 0 67 theme membrane 74:81 arg1 protein 83:89 a zinc-binding monotopic membrane protein 49:89 a zinc-binding monotopic membrane protein 49:89 The Charcot Marie Tooth disease protein LITAF is a zinc-binding monotopic membrane protein. 27582497 1 68 theme endosome-associated 140:158 arg1 LITAF 92:96 LITAF 92:96 LITAF (LPS-induced TNF-activating factor) 92:132 LITAF (LPS-induced TNF-activating factor) is an endosome-associated integral membrane protein important for multivesicular body sorting. 27582497 1 68 theme endosome-associated 140:158 arg1 protein 178:184 an endosome-associated integral membrane protein 137:184 an endosome-associated integral membrane protein important for multivesicular body sorting 137:226 LITAF (LPS-induced TNF-activating factor) is an endosome-associated integral membrane protein important for multivesicular body sorting. 27582497 12 69 theme identical 1672:1680 arg1 topology 1691:1698 identical membrane topology 1672:1698 identical membrane topology 1672:1698 The related human protein, CDIP1 (cell death involved p53 target 1), displays identical membrane topology, suggesting that this mode of membrane integration is conserved in LITAF family proteins. 27582497 11 70 theme membrane 1518:1525 arg1 protein 1527:1533 a monotopic membrane protein 1506:1533 a monotopic membrane protein whose membrane integration is stabilised by a zinc finger 1506:1591 Hence, we conclude that LITAF is a monotopic membrane protein whose membrane integration is stabilised by a zinc finger. 27582497 11 70 theme membrane 1518:1525 arg1 LITAF 1497:1501 LITAF 1497:1501 LITAF 1497:1501 Hence, we conclude that LITAF is a monotopic membrane protein whose membrane integration is stabilised by a zinc finger. 27582497 5 71 theme tail-anchored 723:735 arg1 protein 760:766 a tail-anchored (TA) membrane-spanning protein 721:766 a tail-anchored (TA) membrane-spanning protein 721:766 Here, we have investigated whether LITAF is a tail-anchored (TA) membrane-spanning protein or monotopic membrane protein. 27582497 5 71 theme tail-anchored 723:735 arg1 LITAF 712:716 LITAF 712:716 LITAF 712:716 Here, we have investigated whether LITAF is a tail-anchored (TA) membrane-spanning protein or monotopic membrane protein. 27582497 9 72 theme LITAF 1307:1311 arg1 N- 1287:1288 the N- 1283:1288 the N- 1283:1288 Finally, an immunofluorescence-based latency assay showed that both the N- and C-termini of LITAF are exposed to the cytoplasm. 27582497 10 73 theme membrane 1451:1458 arg1 association 1460:1470 LITAF membrane association 1445:1470 LITAF membrane association 1445:1470 Recombinant LITAF contains 1 mol/mol zinc, while mutation of predicted zinc-binding residues disrupts LITAF membrane association. 27582497 7 74 theme glycosylation 960:972 arg1 reporters 974:982 N-linked glycosylation reporters 951:982 N-linked glycosylation reporters 951:982 Furthermore, introduction of N-linked glycosylation reporters shows that neither the N-terminal nor C-terminal domains of LITAF translocate into the ER lumen. 27582497 7 75 dep domains 1033:1039 arg1 neither 995:1001 neither 995:1001 neither 995:1001 Furthermore, introduction of N-linked glycosylation reporters shows that neither the N-terminal nor C-terminal domains of LITAF translocate into the ER lumen. 27582497 0 76 theme Charcot 4:10 arg1 LITAF 40:44 The Charcot Marie Tooth disease protein LITAF 0:44 The Charcot Marie Tooth disease protein LITAF 0:44 The Charcot Marie Tooth disease protein LITAF is a zinc-binding monotopic membrane protein. 27582497 0 76 theme Charcot 4:10 arg1 protein 83:89 a zinc-binding monotopic membrane protein 49:89 a zinc-binding monotopic membrane protein 49:89 The Charcot Marie Tooth disease protein LITAF is a zinc-binding monotopic membrane protein. 27582497 3 77 theme hydrophobic 432:442 arg1 sequence 444:451 a 22 residue hydrophobic sequence 419:451 a 22 residue hydrophobic sequence 419:451 These mutations map to a highly conserved C-terminal region, termed the LITAF domain, which includes a 22 residue hydrophobic sequence and flanking cysteine-rich regions that contain peptide motifs found in zinc fingers. 27582497 0 78 theme Tooth 18:22 arg1 LITAF 40:44 The Charcot Marie Tooth disease protein LITAF 0:44 The Charcot Marie Tooth disease protein LITAF 0:44 The Charcot Marie Tooth disease protein LITAF is a zinc-binding monotopic membrane protein. 27582497 0 78 theme Tooth 18:22 arg1 protein 83:89 a zinc-binding monotopic membrane protein 49:89 a zinc-binding monotopic membrane protein 49:89 The Charcot Marie Tooth disease protein LITAF is a zinc-binding monotopic membrane protein. 27582497 12 79 theme death 1633:1637 arg1 CDIP1 1621:1625 CDIP1 1621:1625 CDIP1 (cell death involved p53 target 1) 1621:1660 The related human protein, CDIP1 (cell death involved p53 target 1), displays identical membrane topology, suggesting that this mode of membrane integration is conserved in LITAF family proteins. 27582497 12 79 theme death 1633:1637 arg1 target 1652:1657 cell death involved p53 target 1 1628:1659 cell death involved p53 target 1 1628:1659 The related human protein, CDIP1 (cell death involved p53 target 1), displays identical membrane topology, suggesting that this mode of membrane integration is conserved in LITAF family proteins. 27582497 3 80 theme LITAF 390:394 arg1 domain 396:401 the LITAF domain 386:401 the LITAF domain 386:401 These mutations map to a highly conserved C-terminal region, termed the LITAF domain, which includes a 22 residue hydrophobic sequence and flanking cysteine-rich regions that contain peptide motifs found in zinc fingers. 27582497 5 81 theme membrane 781:788 arg1 protein 790:796 monotopic membrane protein 771:796 monotopic membrane protein 771:796 Here, we have investigated whether LITAF is a tail-anchored (TA) membrane-spanning protein or monotopic membrane protein. 27582497 12 82 theme p53 1648:1650 arg1 CDIP1 1621:1625 CDIP1 1621:1625 CDIP1 (cell death involved p53 target 1) 1621:1660 The related human protein, CDIP1 (cell death involved p53 target 1), displays identical membrane topology, suggesting that this mode of membrane integration is conserved in LITAF family proteins. 27582497 12 82 theme p53 1648:1650 arg1 target 1652:1657 cell death involved p53 target 1 1628:1659 cell death involved p53 target 1 1628:1659 The related human protein, CDIP1 (cell death involved p53 target 1), displays identical membrane topology, suggesting that this mode of membrane integration is conserved in LITAF family proteins. 27582497 3 83 theme 22 421:422 arg1 residue 424:430 residue 424:430 residue 424:430 These mutations map to a highly conserved C-terminal region, termed the LITAF domain, which includes a 22 residue hydrophobic sequence and flanking cysteine-rich regions that contain peptide motifs found in zinc fingers. 27582497 8 84 gly glycosylation 1145:1157 arg2 sites 1159:1163 C-terminal glycosylation sites 1134:1163 C-terminal glycosylation sites 1134:1163 Expression in cells of an LITAF construct containing C-terminal glycosylation sites confirms that LITAF is not a TA protein in cells. 27582497 3 85 theme cysteine-rich 466:478 arg1 regions 480:486 flanking cysteine-rich regions 457:486 flanking cysteine-rich regions 457:486 These mutations map to a highly conserved C-terminal region, termed the LITAF domain, which includes a 22 residue hydrophobic sequence and flanking cysteine-rich regions that contain peptide motifs found in zinc fingers. 27582497 12 86 theme related 1598:1604 arg1 CDIP1 1621:1625 CDIP1 1621:1625 CDIP1 (cell death involved p53 target 1) 1621:1660 The related human protein, CDIP1 (cell death involved p53 target 1), displays identical membrane topology, suggesting that this mode of membrane integration is conserved in LITAF family proteins. 27582497 12 86 theme related 1598:1604 arg1 protein 1612:1618 The related human protein 1594:1618 The related human protein 1594:1618 The related human protein, CDIP1 (cell death involved p53 target 1), displays identical membrane topology, suggesting that this mode of membrane integration is conserved in LITAF family proteins. 27582497 8 87 theme construct 1113:1121 arg1 cells 1095:1099 cells 1095:1099 cells of an LITAF construct containing C-terminal glycosylation sites 1095:1163 Expression in cells of an LITAF construct containing C-terminal glycosylation sites confirms that LITAF is not a TA protein in cells. 27582497 6 88 theme ER-derived 854:863 arg1 microsomes 865:874 ER-derived microsomes 854:874 ER-derived microsomes 854:874 When translated in vitro, LITAF integrates poorly into ER-derived microsomes compared with Sec61β, a bona fide TA protein. 27582497 6 89 link ER-derived 854:863 arg1 microsomes 865:874 ER-derived microsomes 854:874 ER-derived microsomes 854:874 When translated in vitro, LITAF integrates poorly into ER-derived microsomes compared with Sec61β, a bona fide TA protein. 27582497 8 90 theme C-terminal 1134:1143 arg1 sites 1159:1163 C-terminal glycosylation sites 1134:1163 C-terminal glycosylation sites 1134:1163 Expression in cells of an LITAF construct containing C-terminal glycosylation sites confirms that LITAF is not a TA protein in cells. 27582497 3 91 theme peptide 501:507 arg1 motifs 509:514 peptide motifs 501:514 peptide motifs found in zinc fingers 501:536 These mutations map to a highly conserved C-terminal region, termed the LITAF domain, which includes a 22 residue hydrophobic sequence and flanking cysteine-rich regions that contain peptide motifs found in zinc fingers. 27582497 6 92 dep bona 900:903 arg1 fide 905:908 fide 905:908 fide 905:908 When translated in vitro, LITAF integrates poorly into ER-derived microsomes compared with Sec61β, a bona fide TA protein. 27582497 10 93 theme 1 mol/mol 1370:1378 arg1 zinc 1380:1383 1 mol/mol zinc 1370:1383 1 mol/mol zinc 1370:1383 Recombinant LITAF contains 1 mol/mol zinc, while mutation of predicted zinc-binding residues disrupts LITAF membrane association. 24280012 5 0 theme 29-amino 550:557 arg1 peptide 571:577 a 29-amino acid signal peptide 548:577 a 29-amino acid signal peptide 548:577 The complete open reading frame (ORF) of GoIL-17A contains 510 base pairs that encode 169 amino acid residues, including a 29-amino acid signal peptide and a single potential N-linked glycosylation site. 24280012 5 1 theme potential 592:600 arg1 site 625:628 a single potential N-linked glycosylation site 583:628 a single potential N-linked glycosylation site 583:628 The complete open reading frame (ORF) of GoIL-17A contains 510 base pairs that encode 169 amino acid residues, including a 29-amino acid signal peptide and a single potential N-linked glycosylation site. 24280012 6 2 theme 18.9kDa 670:676 arg1 weight 660:665 a molecular weight 648:665 a molecular weight of 18.9kDa 648:676 This protein has a molecular weight of 18.9kDa. 24280012 10 3 theme goose 1120:1124 arg1 fibroblasts 1136:1146 goose embryonic fibroblasts 1120:1146 goose embryonic fibroblasts treated with 1-50 μg of rGoIL-17A for 12h 1120:1188 RT-PCR analysis revealed a marked up-regulation of IL-6 and IL-8 mRNA expression in goose embryonic fibroblasts treated with 1-50 μg of rGoIL-17A for 12h. 24280012 5 4 theme N-linked 602:609 arg1 site 625:628 a single potential N-linked glycosylation site 583:628 a single potential N-linked glycosylation site 583:628 The complete open reading frame (ORF) of GoIL-17A contains 510 base pairs that encode 169 amino acid residues, including a 29-amino acid signal peptide and a single potential N-linked glycosylation site. 24280012 7 5 with % 714:714 arg1 rat 789:791 rat 789:791 rat 789:791 The amino acid sequence showed 95.9%, 84.6%, 45.0% and 38.4% similarity with the corresponding duck, chicken, rat, and human IL-17A sequences, respectively. 24280012 7 5 with % 714:714 arg1 chicken 780:786 chicken 780:786 chicken 780:786 The amino acid sequence showed 95.9%, 84.6%, 45.0% and 38.4% similarity with the corresponding duck, chicken, rat, and human IL-17A sequences, respectively. 24280012 7 5 with % 714:714 arg1 duck 774:777 the corresponding duck 756:777 the corresponding duck 756:777 The amino acid sequence showed 95.9%, 84.6%, 45.0% and 38.4% similarity with the corresponding duck, chicken, rat, and human IL-17A sequences, respectively. 24280012 7 5 with % 714:714 arg1 sequences 811:819 human IL-17A sequences 798:819 human IL-17A sequences 798:819 The amino acid sequence showed 95.9%, 84.6%, 45.0% and 38.4% similarity with the corresponding duck, chicken, rat, and human IL-17A sequences, respectively. 24280012 5 6 contain contains 477:484 arg2 site 625:628 a single potential N-linked glycosylation site 583:628 a single potential N-linked glycosylation site 583:628 The complete open reading frame (ORF) of GoIL-17A contains 510 base pairs that encode 169 amino acid residues, including a 29-amino acid signal peptide and a single potential N-linked glycosylation site. 24280012 5 6 contain contains 477:484 arg2 pairs 495:499 510 base pairs 486:499 510 base pairs that encode 169 amino acid residues, including a 29-amino acid signal peptide and a single potential N-linked glycosylation site 486:628 The complete open reading frame (ORF) of GoIL-17A contains 510 base pairs that encode 169 amino acid residues, including a 29-amino acid signal peptide and a single potential N-linked glycosylation site. 24280012 5 6 contain contains 477:484 arg2 residues 528:535 169 amino acid residues 513:535 169 amino acid residues 513:535 The complete open reading frame (ORF) of GoIL-17A contains 510 base pairs that encode 169 amino acid residues, including a 29-amino acid signal peptide and a single potential N-linked glycosylation site. 24280012 5 6 contain contains 477:484 arg1 frame 453:457 The complete open reading frame 427:457 The complete open reading frame (ORF) of GoIL-17A 427:475 The complete open reading frame (ORF) of GoIL-17A contains 510 base pairs that encode 169 amino acid residues, including a 29-amino acid signal peptide and a single potential N-linked glycosylation site. 24280012 5 6 contain contains 477:484 arg2 peptide 571:577 a 29-amino acid signal peptide 548:577 a 29-amino acid signal peptide 548:577 The complete open reading frame (ORF) of GoIL-17A contains 510 base pairs that encode 169 amino acid residues, including a 29-amino acid signal peptide and a single potential N-linked glycosylation site. 24280012 5 6 contain contains 477:484 arg1 ORF 460:462 ORF 460:462 ORF 460:462 The complete open reading frame (ORF) of GoIL-17A contains 510 base pairs that encode 169 amino acid residues, including a 29-amino acid signal peptide and a single potential N-linked glycosylation site. 24280012 7 7 theme amino 683:687 arg1 sequence 694:701 The amino acid sequence 679:701 The amino acid sequence 679:701 The amino acid sequence showed 95.9%, 84.6%, 45.0% and 38.4% similarity with the corresponding duck, chicken, rat, and human IL-17A sequences, respectively. 24280012 10 8 theme IL-6 1087:1090 arg1 expression 1106:1115 IL-6 and IL-8 mRNA expression 1087:1115 IL-6 and IL-8 mRNA expression in goose embryonic fibroblasts treated with 1-50 μg of rGoIL-17A for 12h 1087:1188 RT-PCR analysis revealed a marked up-regulation of IL-6 and IL-8 mRNA expression in goose embryonic fibroblasts treated with 1-50 μg of rGoIL-17A for 12h. 24280012 5 9 theme glycosylation 611:623 arg1 site 625:628 a single potential N-linked glycosylation site 583:628 a single potential N-linked glycosylation site 583:628 The complete open reading frame (ORF) of GoIL-17A contains 510 base pairs that encode 169 amino acid residues, including a 29-amino acid signal peptide and a single potential N-linked glycosylation site. 24280012 5 10 theme acid 559:562 arg1 peptide 571:577 a 29-amino acid signal peptide 548:577 a 29-amino acid signal peptide 548:577 The complete open reading frame (ORF) of GoIL-17A contains 510 base pairs that encode 169 amino acid residues, including a 29-amino acid signal peptide and a single potential N-linked glycosylation site. 24280012 10 11 from fibroblasts 1136:1146 arg1 up-regulation 1070:1082 a marked up-regulation 1061:1082 a marked up-regulation of IL-6 and IL-8 mRNA expression in goose embryonic fibroblasts treated with 1-50 μg of rGoIL-17A for 12h 1061:1188 RT-PCR analysis revealed a marked up-regulation of IL-6 and IL-8 mRNA expression in goose embryonic fibroblasts treated with 1-50 μg of rGoIL-17A for 12h. 24280012 4 12 dep using 352:356 arg1 characterized 412:424 characterized 412:424 characterized 412:424 Recombinant GoIL-17A (rGoIL-17A) was expressed using a baculovirus expression system and then biologically characterized. 24280012 10 13 theme expression 1106:1115 arg1 up-regulation 1070:1082 a marked up-regulation 1061:1082 a marked up-regulation of IL-6 and IL-8 mRNA expression in goose embryonic fibroblasts treated with 1-50 μg of rGoIL-17A for 12h 1061:1188 RT-PCR analysis revealed a marked up-regulation of IL-6 and IL-8 mRNA expression in goose embryonic fibroblasts treated with 1-50 μg of rGoIL-17A for 12h. 24280012 11 14 theme immune 1320:1325 arg1 regulation 1327:1336 immune regulation 1320:1336 immune regulation 1320:1336 The GoIL-17A gene sequence and the biologically active recombinant protein may be useful for understanding the role of IL-17A in immune regulation. 24280012 4 15 theme expression 372:381 arg1 system 383:388 a baculovirus expression system 358:388 a baculovirus expression system 358:388 Recombinant GoIL-17A (rGoIL-17A) was expressed using a baculovirus expression system and then biologically characterized. 24280012 7 16 theme corresponding 760:772 arg1 duck 774:777 the corresponding duck 756:777 the corresponding duck 756:777 The amino acid sequence showed 95.9%, 84.6%, 45.0% and 38.4% similarity with the corresponding duck, chicken, rat, and human IL-17A sequences, respectively. 24280012 8 17 theme cysteine 854:861 arg1 residues 863:870 The six conserved cysteine residues 836:870 The six conserved cysteine residues 836:870 The six conserved cysteine residues were also observed in GoIL-17A. 24280012 4 18 theme baculovirus 360:370 arg1 system 383:388 a baculovirus expression system 358:388 a baculovirus expression system 358:388 Recombinant GoIL-17A (rGoIL-17A) was expressed using a baculovirus expression system and then biologically characterized. 24280012 9 19 theme biological 964:973 arg1 activities 975:984 its biological activities 960:984 its biological activities in goose embryonic fibroblasts 960:1015 A recombinant, mature form of GoIL-17A was produced and its biological activities in goose embryonic fibroblasts were investigated. 24280012 9 20 theme recombinant 906:916 arg1 form 926:929 A recombinant, mature form 904:929 A recombinant, mature form of GoIL-17A 904:941 A recombinant, mature form of GoIL-17A was produced and its biological activities in goose embryonic fibroblasts were investigated. 24280012 9 21 dep recombinant 906:916 arg1 mature 919:924 mature 919:924 mature 919:924 A recombinant, mature form of GoIL-17A was produced and its biological activities in goose embryonic fibroblasts were investigated. 24280012 5 22 theme acid 523:526 arg1 peptide 571:577 a 29-amino acid signal peptide 548:577 a 29-amino acid signal peptide 548:577 The complete open reading frame (ORF) of GoIL-17A contains 510 base pairs that encode 169 amino acid residues, including a 29-amino acid signal peptide and a single potential N-linked glycosylation site. 24280012 5 22 theme acid 523:526 arg1 pairs 495:499 510 base pairs 486:499 510 base pairs that encode 169 amino acid residues, including a 29-amino acid signal peptide and a single potential N-linked glycosylation site 486:628 The complete open reading frame (ORF) of GoIL-17A contains 510 base pairs that encode 169 amino acid residues, including a 29-amino acid signal peptide and a single potential N-linked glycosylation site. 24280012 5 22 theme acid 523:526 arg1 residues 528:535 169 amino acid residues 513:535 169 amino acid residues 513:535 The complete open reading frame (ORF) of GoIL-17A contains 510 base pairs that encode 169 amino acid residues, including a 29-amino acid signal peptide and a single potential N-linked glycosylation site. 24280012 5 22 theme acid 523:526 arg1 site 625:628 a single potential N-linked glycosylation site 583:628 a single potential N-linked glycosylation site 583:628 The complete open reading frame (ORF) of GoIL-17A contains 510 base pairs that encode 169 amino acid residues, including a 29-amino acid signal peptide and a single potential N-linked glycosylation site. 24280012 6 23 theme molecular 650:658 arg1 weight 660:665 a molecular weight 648:665 a molecular weight of 18.9kDa 648:676 This protein has a molecular weight of 18.9kDa. 24280012 11 24 theme active 1239:1244 arg1 protein 1258:1264 the biologically active recombinant protein 1222:1264 the biologically active recombinant protein 1222:1264 The GoIL-17A gene sequence and the biologically active recombinant protein may be useful for understanding the role of IL-17A in immune regulation. 24280012 11 24 theme active 1239:1244 arg1 useful 1273:1278 useful 1273:1278 useful 1273:1278 The GoIL-17A gene sequence and the biologically active recombinant protein may be useful for understanding the role of IL-17A in immune regulation. 24280012 10 25 from up-regulation 1070:1082 arg1 fibroblasts 1136:1146 goose embryonic fibroblasts 1120:1146 goose embryonic fibroblasts treated with 1-50 μg of rGoIL-17A for 12h 1120:1188 RT-PCR analysis revealed a marked up-regulation of IL-6 and IL-8 mRNA expression in goose embryonic fibroblasts treated with 1-50 μg of rGoIL-17A for 12h. 24280012 11 26 theme gene 1204:1207 arg1 sequence 1209:1216 The GoIL-17A gene sequence 1191:1216 The GoIL-17A gene sequence 1191:1216 The GoIL-17A gene sequence and the biologically active recombinant protein may be useful for understanding the role of IL-17A in immune regulation. 24280012 11 26 theme gene 1204:1207 arg1 useful 1273:1278 useful 1273:1278 useful 1273:1278 The GoIL-17A gene sequence and the biologically active recombinant protein may be useful for understanding the role of IL-17A in immune regulation. 24280012 5 27 theme GoIL-17A 468:475 arg1 frame 453:457 The complete open reading frame 427:457 The complete open reading frame (ORF) of GoIL-17A 427:475 The complete open reading frame (ORF) of GoIL-17A contains 510 base pairs that encode 169 amino acid residues, including a 29-amino acid signal peptide and a single potential N-linked glycosylation site. 24280012 5 27 theme GoIL-17A 468:475 arg1 ORF 460:462 ORF 460:462 ORF 460:462 The complete open reading frame (ORF) of GoIL-17A contains 510 base pairs that encode 169 amino acid residues, including a 29-amino acid signal peptide and a single potential N-linked glycosylation site. 24280012 11 28 theme recombinant 1246:1256 arg1 protein 1258:1264 the biologically active recombinant protein 1222:1264 the biologically active recombinant protein 1222:1264 The GoIL-17A gene sequence and the biologically active recombinant protein may be useful for understanding the role of IL-17A in immune regulation. 24280012 11 28 theme recombinant 1246:1256 arg1 useful 1273:1278 useful 1273:1278 useful 1273:1278 The GoIL-17A gene sequence and the biologically active recombinant protein may be useful for understanding the role of IL-17A in immune regulation. 24280012 5 29 theme single 585:590 arg1 site 625:628 a single potential N-linked glycosylation site 583:628 a single potential N-linked glycosylation site 583:628 The complete open reading frame (ORF) of GoIL-17A contains 510 base pairs that encode 169 amino acid residues, including a 29-amino acid signal peptide and a single potential N-linked glycosylation site. 24280012 7 30 with % 728:728 arg1 rat 789:791 rat 789:791 rat 789:791 The amino acid sequence showed 95.9%, 84.6%, 45.0% and 38.4% similarity with the corresponding duck, chicken, rat, and human IL-17A sequences, respectively. 24280012 7 30 with % 728:728 arg1 chicken 780:786 chicken 780:786 chicken 780:786 The amino acid sequence showed 95.9%, 84.6%, 45.0% and 38.4% similarity with the corresponding duck, chicken, rat, and human IL-17A sequences, respectively. 24280012 7 30 with % 728:728 arg1 duck 774:777 the corresponding duck 756:777 the corresponding duck 756:777 The amino acid sequence showed 95.9%, 84.6%, 45.0% and 38.4% similarity with the corresponding duck, chicken, rat, and human IL-17A sequences, respectively. 24280012 7 30 with % 728:728 arg1 sequences 811:819 human IL-17A sequences 798:819 human IL-17A sequences 798:819 The amino acid sequence showed 95.9%, 84.6%, 45.0% and 38.4% similarity with the corresponding duck, chicken, rat, and human IL-17A sequences, respectively. 24280012 5 31 theme open 440:443 arg1 frame 453:457 The complete open reading frame 427:457 The complete open reading frame (ORF) of GoIL-17A 427:475 The complete open reading frame (ORF) of GoIL-17A contains 510 base pairs that encode 169 amino acid residues, including a 29-amino acid signal peptide and a single potential N-linked glycosylation site. 24280012 5 31 theme open 440:443 arg1 ORF 460:462 ORF 460:462 ORF 460:462 The complete open reading frame (ORF) of GoIL-17A contains 510 base pairs that encode 169 amino acid residues, including a 29-amino acid signal peptide and a single potential N-linked glycosylation site. 24280012 5 32 gly glycosylation 611:623 arg2 site 625:628 a single potential N-linked glycosylation site 583:628 a single potential N-linked glycosylation site 583:628 The complete open reading frame (ORF) of GoIL-17A contains 510 base pairs that encode 169 amino acid residues, including a 29-amino acid signal peptide and a single potential N-linked glycosylation site. 24280012 10 33 theme RT-PCR 1036:1041 arg1 analysis 1043:1050 RT-PCR analysis 1036:1050 RT-PCR analysis 1036:1050 RT-PCR analysis revealed a marked up-regulation of IL-6 and IL-8 mRNA expression in goose embryonic fibroblasts treated with 1-50 μg of rGoIL-17A for 12h. 24280012 3 34 theme goose 248:252 arg1 gene 272:275 the goose IL-17A (GoIL-17A) gene 244:275 the goose IL-17A (GoIL-17A) gene 244:275 In this study, the cDNA of the goose IL-17A (GoIL-17A) gene was cloned from thymocytes. 24280012 5 35 theme signal 564:569 arg1 peptide 571:577 a 29-amino acid signal peptide 548:577 a 29-amino acid signal peptide 548:577 The complete open reading frame (ORF) of GoIL-17A contains 510 base pairs that encode 169 amino acid residues, including a 29-amino acid signal peptide and a single potential N-linked glycosylation site. 24280012 5 36 theme reading 445:451 arg1 frame 453:457 The complete open reading frame 427:457 The complete open reading frame (ORF) of GoIL-17A 427:475 The complete open reading frame (ORF) of GoIL-17A contains 510 base pairs that encode 169 amino acid residues, including a 29-amino acid signal peptide and a single potential N-linked glycosylation site. 24280012 5 36 theme reading 445:451 arg1 ORF 460:462 ORF 460:462 ORF 460:462 The complete open reading frame (ORF) of GoIL-17A contains 510 base pairs that encode 169 amino acid residues, including a 29-amino acid signal peptide and a single potential N-linked glycosylation site. 24280012 10 37 theme mRNA 1101:1104 arg1 expression 1106:1115 IL-6 and IL-8 mRNA expression 1087:1115 IL-6 and IL-8 mRNA expression in goose embryonic fibroblasts treated with 1-50 μg of rGoIL-17A for 12h 1087:1188 RT-PCR analysis revealed a marked up-regulation of IL-6 and IL-8 mRNA expression in goose embryonic fibroblasts treated with 1-50 μg of rGoIL-17A for 12h. 24280012 3 38 theme IL-17A 254:259 arg1 gene 272:275 the goose IL-17A (GoIL-17A) gene 244:275 the goose IL-17A (GoIL-17A) gene 244:275 In this study, the cDNA of the goose IL-17A (GoIL-17A) gene was cloned from thymocytes. 24280012 7 39 theme 38.4 734:737 arg1 % 738:738 % 738:738 % 738:738 The amino acid sequence showed 95.9%, 84.6%, 45.0% and 38.4% similarity with the corresponding duck, chicken, rat, and human IL-17A sequences, respectively. 24280012 9 40 theme goose 989:993 arg1 fibroblasts 1005:1015 goose embryonic fibroblasts 989:1015 goose embryonic fibroblasts 989:1015 A recombinant, mature form of GoIL-17A was produced and its biological activities in goose embryonic fibroblasts were investigated. 24280012 0 41 theme interleukin-17A 38:52 arg1 cDNA 54:57 goose interleukin-17A cDNA 32:57 goose interleukin-17A cDNA 32:57 Cloning and characterization of goose interleukin-17A cDNA. 24280012 11 42 theme GoIL-17A 1195:1202 arg1 sequence 1209:1216 The GoIL-17A gene sequence 1191:1216 The GoIL-17A gene sequence 1191:1216 The GoIL-17A gene sequence and the biologically active recombinant protein may be useful for understanding the role of IL-17A in immune regulation. 24280012 11 42 theme GoIL-17A 1195:1202 arg1 useful 1273:1278 useful 1273:1278 useful 1273:1278 The GoIL-17A gene sequence and the biologically active recombinant protein may be useful for understanding the role of IL-17A in immune regulation. 24280012 2 43 theme important 167:175 arg1 roles 177:181 important roles 167:181 important roles 167:181 IL-17A plays important roles in inflammation and host defense. 24280012 7 44 theme % 738:738 arg1 similarity 740:749 38.4% similarity 734:749 38.4% similarity with the corresponding duck, chicken, rat, and human IL-17A sequences 734:819 The amino acid sequence showed 95.9%, 84.6%, 45.0% and 38.4% similarity with the corresponding duck, chicken, rat, and human IL-17A sequences, respectively. 24280012 0 45 theme goose 32:36 arg1 cDNA 54:57 goose interleukin-17A cDNA 32:57 goose interleukin-17A cDNA 32:57 Cloning and characterization of goose interleukin-17A cDNA. 24280012 7 46 theme human 798:802 arg1 sequences 811:819 human IL-17A sequences 798:819 human IL-17A sequences 798:819 The amino acid sequence showed 95.9%, 84.6%, 45.0% and 38.4% similarity with the corresponding duck, chicken, rat, and human IL-17A sequences, respectively. 24280012 7 47 with similarity 740:749 arg1 rat 789:791 rat 789:791 rat 789:791 The amino acid sequence showed 95.9%, 84.6%, 45.0% and 38.4% similarity with the corresponding duck, chicken, rat, and human IL-17A sequences, respectively. 24280012 7 47 with similarity 740:749 arg1 chicken 780:786 chicken 780:786 chicken 780:786 The amino acid sequence showed 95.9%, 84.6%, 45.0% and 38.4% similarity with the corresponding duck, chicken, rat, and human IL-17A sequences, respectively. 24280012 7 47 with similarity 740:749 arg1 duck 774:777 the corresponding duck 756:777 the corresponding duck 756:777 The amino acid sequence showed 95.9%, 84.6%, 45.0% and 38.4% similarity with the corresponding duck, chicken, rat, and human IL-17A sequences, respectively. 24280012 7 47 with similarity 740:749 arg1 sequences 811:819 human IL-17A sequences 798:819 human IL-17A sequences 798:819 The amino acid sequence showed 95.9%, 84.6%, 45.0% and 38.4% similarity with the corresponding duck, chicken, rat, and human IL-17A sequences, respectively. 24280012 8 48 located observed 882:889 arg2 residues 863:870 The six conserved cysteine residues 836:870 The six conserved cysteine residues 836:870 The six conserved cysteine residues were also observed in GoIL-17A. 24280012 8 48 located observed 882:889 arg1 GoIL-17A 894:901 GoIL-17A 894:901 GoIL-17A 894:901 The six conserved cysteine residues were also observed in GoIL-17A. 24280012 4 49 theme Recombinant 305:315 arg1 rGoIL-17A 327:335 rGoIL-17A 327:335 rGoIL-17A 327:335 Recombinant GoIL-17A (rGoIL-17A) was expressed using a baculovirus expression system and then biologically characterized. 24280012 4 49 theme Recombinant 305:315 arg1 GoIL-17A 317:324 Recombinant GoIL-17A 305:324 Recombinant GoIL-17A (rGoIL-17A) 305:336 Recombinant GoIL-17A (rGoIL-17A) was expressed using a baculovirus expression system and then biologically characterized. 24280012 5 50 link N-linked 602:609 arg1 site 625:628 a single potential N-linked glycosylation site 583:628 a single potential N-linked glycosylation site 583:628 The complete open reading frame (ORF) of GoIL-17A contains 510 base pairs that encode 169 amino acid residues, including a 29-amino acid signal peptide and a single potential N-linked glycosylation site. 24280012 10 51 theme marked 1063:1068 arg1 up-regulation 1070:1082 a marked up-regulation 1061:1082 a marked up-regulation of IL-6 and IL-8 mRNA expression in goose embryonic fibroblasts treated with 1-50 μg of rGoIL-17A for 12h 1061:1188 RT-PCR analysis revealed a marked up-regulation of IL-6 and IL-8 mRNA expression in goose embryonic fibroblasts treated with 1-50 μg of rGoIL-17A for 12h. 24280012 10 52 from expression 1106:1115 arg1 fibroblasts 1136:1146 goose embryonic fibroblasts 1120:1146 goose embryonic fibroblasts treated with 1-50 μg of rGoIL-17A for 12h 1120:1188 RT-PCR analysis revealed a marked up-regulation of IL-6 and IL-8 mRNA expression in goose embryonic fibroblasts treated with 1-50 μg of rGoIL-17A for 12h. 24280012 10 53 theme embryonic 1126:1134 arg1 fibroblasts 1136:1146 goose embryonic fibroblasts 1120:1146 goose embryonic fibroblasts treated with 1-50 μg of rGoIL-17A for 12h 1120:1188 RT-PCR analysis revealed a marked up-regulation of IL-6 and IL-8 mRNA expression in goose embryonic fibroblasts treated with 1-50 μg of rGoIL-17A for 12h. 24280012 1 54 theme proinflammatory 98:112 arg1 Interleukin-17 60:73 Interleukin-17 60:73 Interleukin-17 (IL-17 or IL-17A) 60:91 Interleukin-17 (IL-17 or IL-17A) is a proinflammatory cytokine produced by activated T cells. 24280012 1 54 theme proinflammatory 98:112 arg1 cytokine 114:121 a proinflammatory cytokine 96:121 a proinflammatory cytokine produced by activated T cells 96:151 Interleukin-17 (IL-17 or IL-17A) is a proinflammatory cytokine produced by activated T cells. 24280012 0 55 theme cDNA 54:57 arg1 characterization 12:27 characterization 12:27 characterization 12:27 Cloning and characterization of goose interleukin-17A cDNA. 24280012 0 55 theme cDNA 54:57 arg1 Cloning 0:6 Cloning 0:6 Cloning 0:6 Cloning and characterization of goose interleukin-17A cDNA. 24280012 3 56 theme gene 272:275 arg1 cDNA 236:239 the cDNA 232:239 the cDNA of the goose IL-17A (GoIL-17A) gene 232:275 In this study, the cDNA of the goose IL-17A (GoIL-17A) gene was cloned from thymocytes. 24280012 2 57 theme host 203:206 arg1 defense 208:214 host defense 203:214 host defense 203:214 IL-17A plays important roles in inflammation and host defense. 24280012 7 58 theme IL-17A 804:809 arg1 sequences 811:819 human IL-17A sequences 798:819 human IL-17A sequences 798:819 The amino acid sequence showed 95.9%, 84.6%, 45.0% and 38.4% similarity with the corresponding duck, chicken, rat, and human IL-17A sequences, respectively. 24280012 9 59 from activities 975:984 arg1 fibroblasts 1005:1015 goose embryonic fibroblasts 989:1015 goose embryonic fibroblasts 989:1015 A recombinant, mature form of GoIL-17A was produced and its biological activities in goose embryonic fibroblasts were investigated. 24280012 5 60 theme amino 517:521 arg1 peptide 571:577 a 29-amino acid signal peptide 548:577 a 29-amino acid signal peptide 548:577 The complete open reading frame (ORF) of GoIL-17A contains 510 base pairs that encode 169 amino acid residues, including a 29-amino acid signal peptide and a single potential N-linked glycosylation site. 24280012 5 60 theme amino 517:521 arg1 pairs 495:499 510 base pairs 486:499 510 base pairs that encode 169 amino acid residues, including a 29-amino acid signal peptide and a single potential N-linked glycosylation site 486:628 The complete open reading frame (ORF) of GoIL-17A contains 510 base pairs that encode 169 amino acid residues, including a 29-amino acid signal peptide and a single potential N-linked glycosylation site. 24280012 5 60 theme amino 517:521 arg1 residues 528:535 169 amino acid residues 513:535 169 amino acid residues 513:535 The complete open reading frame (ORF) of GoIL-17A contains 510 base pairs that encode 169 amino acid residues, including a 29-amino acid signal peptide and a single potential N-linked glycosylation site. 24280012 5 60 theme amino 517:521 arg1 site 625:628 a single potential N-linked glycosylation site 583:628 a single potential N-linked glycosylation site 583:628 The complete open reading frame (ORF) of GoIL-17A contains 510 base pairs that encode 169 amino acid residues, including a 29-amino acid signal peptide and a single potential N-linked glycosylation site. 24280012 1 61 dep Interleukin-17 60:73 arg1 IL-17 76:80 IL-17 76:80 IL-17 76:80 Interleukin-17 (IL-17 or IL-17A) is a proinflammatory cytokine produced by activated T cells. 24280012 1 61 dep Interleukin-17 60:73 arg1 IL-17A 85:90 IL-17A 85:90 IL-17A 85:90 Interleukin-17 (IL-17 or IL-17A) is a proinflammatory cytokine produced by activated T cells. 24280012 10 62 theme IL-8 1096:1099 arg1 expression 1106:1115 IL-6 and IL-8 mRNA expression 1087:1115 IL-6 and IL-8 mRNA expression in goose embryonic fibroblasts treated with 1-50 μg of rGoIL-17A for 12h 1087:1188 RT-PCR analysis revealed a marked up-regulation of IL-6 and IL-8 mRNA expression in goose embryonic fibroblasts treated with 1-50 μg of rGoIL-17A for 12h. 24280012 3 63 theme GoIL-17A 262:269 arg1 gene 272:275 the goose IL-17A (GoIL-17A) gene 244:275 the goose IL-17A (GoIL-17A) gene 244:275 In this study, the cDNA of the goose IL-17A (GoIL-17A) gene was cloned from thymocytes. 24280012 8 64 theme conserved 844:852 arg1 residues 863:870 The six conserved cysteine residues 836:870 The six conserved cysteine residues 836:870 The six conserved cysteine residues were also observed in GoIL-17A. 24280012 9 65 theme embryonic 995:1003 arg1 fibroblasts 1005:1015 goose embryonic fibroblasts 989:1015 goose embryonic fibroblasts 989:1015 A recombinant, mature form of GoIL-17A was produced and its biological activities in goose embryonic fibroblasts were investigated. 24280012 7 66 with % 721:721 arg1 rat 789:791 rat 789:791 rat 789:791 The amino acid sequence showed 95.9%, 84.6%, 45.0% and 38.4% similarity with the corresponding duck, chicken, rat, and human IL-17A sequences, respectively. 24280012 7 66 with % 721:721 arg1 chicken 780:786 chicken 780:786 chicken 780:786 The amino acid sequence showed 95.9%, 84.6%, 45.0% and 38.4% similarity with the corresponding duck, chicken, rat, and human IL-17A sequences, respectively. 24280012 7 66 with % 721:721 arg1 duck 774:777 the corresponding duck 756:777 the corresponding duck 756:777 The amino acid sequence showed 95.9%, 84.6%, 45.0% and 38.4% similarity with the corresponding duck, chicken, rat, and human IL-17A sequences, respectively. 24280012 7 66 with % 721:721 arg1 sequences 811:819 human IL-17A sequences 798:819 human IL-17A sequences 798:819 The amino acid sequence showed 95.9%, 84.6%, 45.0% and 38.4% similarity with the corresponding duck, chicken, rat, and human IL-17A sequences, respectively. 24280012 10 67 theme 1-50 1161:1164 arg1 μg 1166:1167 1-50 μg 1161:1167 1-50 μg of rGoIL-17A for 12h 1161:1188 RT-PCR analysis revealed a marked up-regulation of IL-6 and IL-8 mRNA expression in goose embryonic fibroblasts treated with 1-50 μg of rGoIL-17A for 12h. 24280012 10 68 theme rGoIL-17A 1172:1180 arg1 μg 1166:1167 1-50 μg 1161:1167 1-50 μg of rGoIL-17A for 12h 1161:1188 RT-PCR analysis revealed a marked up-regulation of IL-6 and IL-8 mRNA expression in goose embryonic fibroblasts treated with 1-50 μg of rGoIL-17A for 12h. 24280012 1 69 theme activated 135:143 arg1 cells 147:151 activated T cells 135:151 activated T cells 135:151 Interleukin-17 (IL-17 or IL-17A) is a proinflammatory cytokine produced by activated T cells. 24280012 5 70 theme complete 431:438 arg1 frame 453:457 The complete open reading frame 427:457 The complete open reading frame (ORF) of GoIL-17A 427:475 The complete open reading frame (ORF) of GoIL-17A contains 510 base pairs that encode 169 amino acid residues, including a 29-amino acid signal peptide and a single potential N-linked glycosylation site. 24280012 5 70 theme complete 431:438 arg1 ORF 460:462 ORF 460:462 ORF 460:462 The complete open reading frame (ORF) of GoIL-17A contains 510 base pairs that encode 169 amino acid residues, including a 29-amino acid signal peptide and a single potential N-linked glycosylation site. 24280012 7 71 theme acid 689:692 arg1 sequence 694:701 The amino acid sequence 679:701 The amino acid sequence 679:701 The amino acid sequence showed 95.9%, 84.6%, 45.0% and 38.4% similarity with the corresponding duck, chicken, rat, and human IL-17A sequences, respectively. 24280012 6 72 contain has 644:646 arg1 protein 636:642 This protein 631:642 This protein 631:642 This protein has a molecular weight of 18.9kDa. 24280012 6 72 contain has 644:646 arg2 weight 660:665 a molecular weight 648:665 a molecular weight of 18.9kDa 648:676 This protein has a molecular weight of 18.9kDa. 24280012 11 73 from role 1302:1305 arg1 regulation 1327:1336 immune regulation 1320:1336 immune regulation 1320:1336 The GoIL-17A gene sequence and the biologically active recombinant protein may be useful for understanding the role of IL-17A in immune regulation. 24280012 5 74 theme base 490:493 arg1 peptide 571:577 a 29-amino acid signal peptide 548:577 a 29-amino acid signal peptide 548:577 The complete open reading frame (ORF) of GoIL-17A contains 510 base pairs that encode 169 amino acid residues, including a 29-amino acid signal peptide and a single potential N-linked glycosylation site. 24280012 5 74 theme base 490:493 arg1 pairs 495:499 510 base pairs 486:499 510 base pairs that encode 169 amino acid residues, including a 29-amino acid signal peptide and a single potential N-linked glycosylation site 486:628 The complete open reading frame (ORF) of GoIL-17A contains 510 base pairs that encode 169 amino acid residues, including a 29-amino acid signal peptide and a single potential N-linked glycosylation site. 24280012 5 74 theme base 490:493 arg1 residues 528:535 169 amino acid residues 513:535 169 amino acid residues 513:535 The complete open reading frame (ORF) of GoIL-17A contains 510 base pairs that encode 169 amino acid residues, including a 29-amino acid signal peptide and a single potential N-linked glycosylation site. 24280012 5 74 theme base 490:493 arg1 site 625:628 a single potential N-linked glycosylation site 583:628 a single potential N-linked glycosylation site 583:628 The complete open reading frame (ORF) of GoIL-17A contains 510 base pairs that encode 169 amino acid residues, including a 29-amino acid signal peptide and a single potential N-linked glycosylation site. 24280012 1 75 theme T 145:145 arg1 cells 147:151 activated T cells 135:151 activated T cells 135:151 Interleukin-17 (IL-17 or IL-17A) is a proinflammatory cytokine produced by activated T cells. 24280012 9 76 theme GoIL-17A 934:941 arg1 form 926:929 A recombinant, mature form 904:929 A recombinant, mature form of GoIL-17A 904:941 A recombinant, mature form of GoIL-17A was produced and its biological activities in goose embryonic fibroblasts were investigated. 24280012 11 77 theme IL-17A 1310:1315 arg1 role 1302:1305 the role 1298:1305 the role of IL-17A in immune regulation 1298:1336 The GoIL-17A gene sequence and the biologically active recombinant protein may be useful for understanding the role of IL-17A in immune regulation. 28537384 3 0 theme G 729:729 arg1 digest 659:664 digest 659:664 digest of horseradish peroxidase (HRP) and human serum immunoglobulin G (IgG), respectively 659:749 By using this nanocomposite, 16 and 31 glycopeptides were efficiently extracted from digest of horseradish peroxidase (HRP) and human serum immunoglobulin G (IgG), respectively. 28537384 3 1 theme human 702:706 arg1 IgG 732:734 IgG 732:734 IgG 732:734 By using this nanocomposite, 16 and 31 glycopeptides were efficiently extracted from digest of horseradish peroxidase (HRP) and human serum immunoglobulin G (IgG), respectively. 28537384 3 1 theme human 702:706 arg1 G 729:729 human serum immunoglobulin G 702:729 human serum immunoglobulin G (IgG) 702:735 By using this nanocomposite, 16 and 31 glycopeptides were efficiently extracted from digest of horseradish peroxidase (HRP) and human serum immunoglobulin G (IgG), respectively. 28537384 6 2 theme best 1308:1311 arg1 result 1313:1318 the best result 1304:1318 the best result 1304:1318 Compared with those of previously reported hydrophilic methods, to our knowledge, it was the best result. 28537384 6 2 theme best 1308:1311 arg1 it 1297:1298 it 1297:1298 it 1297:1298 Compared with those of previously reported hydrophilic methods, to our knowledge, it was the best result. 28537384 1 3 theme Au 270:271 arg1 nanoparticles 273:285 Au nanoparticles 270:285 Au nanoparticles 270:285 Cysteine-functionalized metal-organic framework (MOF) was synthesized via a common and facile two-step method of in situ loading of Au nanoparticles on amino-derived MOF followed by l-cysteine (Cys) immobilization. 28537384 2 4 located observed 472:479 arg1 enrichment 488:497 the enrichment 484:497 the enrichment of N-linked glycopeptides in both model glycoprotein and HeLa cell lysate 484:571 Owing to the large specific surface area and ultrahigh hydrophilicity of this nanocomposite, excellent performance was observed in the enrichment of N-linked glycopeptides in both model glycoprotein and HeLa cell lysate. 28537384 2 4 located observed 472:479 arg2 performance 456:466 excellent performance 446:466 excellent performance 446:466 Owing to the large specific surface area and ultrahigh hydrophilicity of this nanocomposite, excellent performance was observed in the enrichment of N-linked glycopeptides in both model glycoprotein and HeLa cell lysate. 28537384 1 5 from MOF 304:306 arg1 method 241:246 a common and facile two-step method 212:246 a common and facile two-step method of in situ loading of Au nanoparticles on amino-derived MOF followed by l-cysteine (Cys) immobilization 212:350 Cysteine-functionalized metal-organic framework (MOF) was synthesized via a common and facile two-step method of in situ loading of Au nanoparticles on amino-derived MOF followed by l-cysteine (Cys) immobilization. 28537384 1 6 theme common 214:219 arg1 method 241:246 a common and facile two-step method 212:246 a common and facile two-step method of in situ loading of Au nanoparticles on amino-derived MOF followed by l-cysteine (Cys) immobilization 212:350 Cysteine-functionalized metal-organic framework (MOF) was synthesized via a common and facile two-step method of in situ loading of Au nanoparticles on amino-derived MOF followed by l-cysteine (Cys) immobilization. 28537384 4 7 theme molar 870:874 arg1 ratio 876:880 molar ratio 870:880 molar ratio of IgG and bovine serum albumin (BSA) digest 870:925 The short incubation time (5 min), large binding capacity (150 mg/g, IgG digest to material), good selectivity (1:50, molar ratio of IgG and bovine serum albumin (BSA) digest), high recovery (over 80%), and low detection limit (1 fmol) ensure the effectiveness and robustness of MIL-101(NH2)@Au-Cys in complex HeLa cell lysate. 28537384 3 8 gly glycopeptides 613:625 arg2 glycopeptides 613:625 16 and 31 glycopeptides 603:625 16 and 31 glycopeptides 603:625 By using this nanocomposite, 16 and 31 glycopeptides were efficiently extracted from digest of horseradish peroxidase (HRP) and human serum immunoglobulin G (IgG), respectively. 28537384 1 9 theme facile 225:230 arg1 method 241:246 a common and facile two-step method 212:246 a common and facile two-step method of in situ loading of Au nanoparticles on amino-derived MOF followed by l-cysteine (Cys) immobilization 212:350 Cysteine-functionalized metal-organic framework (MOF) was synthesized via a common and facile two-step method of in situ loading of Au nanoparticles on amino-derived MOF followed by l-cysteine (Cys) immobilization. 28537384 4 10 dep IgG 885:887 arg1 digest 920:925 digest 920:925 digest 920:925 The short incubation time (5 min), large binding capacity (150 mg/g, IgG digest to material), good selectivity (1:50, molar ratio of IgG and bovine serum albumin (BSA) digest), high recovery (over 80%), and low detection limit (1 fmol) ensure the effectiveness and robustness of MIL-101(NH2)@Au-Cys in complex HeLa cell lysate. 28537384 1 11 dep in 251:252 arg1 situ 254:257 situ 254:257 situ 254:257 Cysteine-functionalized metal-organic framework (MOF) was synthesized via a common and facile two-step method of in situ loading of Au nanoparticles on amino-derived MOF followed by l-cysteine (Cys) immobilization. 28537384 2 12 link N-linked 502:509 arg1 glycopeptides 511:523 N-linked glycopeptides 502:523 N-linked glycopeptides 502:523 Owing to the large specific surface area and ultrahigh hydrophilicity of this nanocomposite, excellent performance was observed in the enrichment of N-linked glycopeptides in both model glycoprotein and HeLa cell lysate. 28537384 1 13 from loading 259:265 arg1 MOF 304:306 amino-derived MOF 290:306 amino-derived MOF followed by l-cysteine (Cys) immobilization 290:350 Cysteine-functionalized metal-organic framework (MOF) was synthesized via a common and facile two-step method of in situ loading of Au nanoparticles on amino-derived MOF followed by l-cysteine (Cys) immobilization. 28537384 1 14 theme Cysteine-functionalized 138:160 arg1 MOF 187:189 MOF 187:189 MOF 187:189 Cysteine-functionalized metal-organic framework (MOF) was synthesized via a common and facile two-step method of in situ loading of Au nanoparticles on amino-derived MOF followed by l-cysteine (Cys) immobilization. 28537384 1 14 theme Cysteine-functionalized 138:160 arg1 framework 176:184 Cysteine-functionalized metal-organic framework 138:184 Cysteine-functionalized metal-organic framework (MOF) 138:190 Cysteine-functionalized metal-organic framework (MOF) was synthesized via a common and facile two-step method of in situ loading of Au nanoparticles on amino-derived MOF followed by l-cysteine (Cys) immobilization. 28537384 7 15 theme sample 1435:1440 arg1 preparation 1442:1452 sample preparation 1435:1452 sample preparation 1435:1452 This work paves a new way for fast functionalization of MOF and also provides a novel idea for material design in sample preparation, especially in glycoproteome and related analysis. 28537384 4 16 theme Au-Cys 1044:1049 arg1 effectiveness 999:1011 the effectiveness 995:1011 the effectiveness 995:1011 The short incubation time (5 min), large binding capacity (150 mg/g, IgG digest to material), good selectivity (1:50, molar ratio of IgG and bovine serum albumin (BSA) digest), high recovery (over 80%), and low detection limit (1 fmol) ensure the effectiveness and robustness of MIL-101(NH2)@Au-Cys in complex HeLa cell lysate. 28537384 4 16 theme Au-Cys 1044:1049 arg1 robustness 1017:1026 robustness 1017:1026 robustness 1017:1026 The short incubation time (5 min), large binding capacity (150 mg/g, IgG digest to material), good selectivity (1:50, molar ratio of IgG and bovine serum albumin (BSA) digest), high recovery (over 80%), and low detection limit (1 fmol) ensure the effectiveness and robustness of MIL-101(NH2)@Au-Cys in complex HeLa cell lysate. 28537384 0 17 theme Efficient 75:83 arg1 Enrichment 85:94 High Efficient Enrichment 70:94 High Efficient Enrichment 70:94 Cysteine-Functionalized Metal-Organic Framework: Facile Synthesis and High Efficient Enrichment of N-Linked Glycopeptides in Cell Lysate. 28537384 2 18 theme glycopeptides 511:523 arg1 enrichment 488:497 the enrichment 484:497 the enrichment of N-linked glycopeptides in both model glycoprotein and HeLa cell lysate 484:571 Owing to the large specific surface area and ultrahigh hydrophilicity of this nanocomposite, excellent performance was observed in the enrichment of N-linked glycopeptides in both model glycoprotein and HeLa cell lysate. 28537384 5 19 theme 1123 1093:1096 arg1 sites 1114:1118 1123 N-glycosylation sites 1093:1118 1123 N-glycosylation sites corresponding to 1069 N-glycopeptides and 614 N-glycoproteins 1093:1180 As a result, 1123 N-glycosylation sites corresponding to 1069 N-glycopeptides and 614 N-glycoproteins were identified from the lysate. 28537384 5 19 theme 1123 1093:1096 arg1 result 1085:1090 a result 1083:1090 a result 1083:1090 As a result, 1123 N-glycosylation sites corresponding to 1069 N-glycopeptides and 614 N-glycoproteins were identified from the lysate. 28537384 7 20 theme novel 1401:1405 arg1 idea 1407:1410 a novel idea 1399:1410 a novel idea 1399:1410 This work paves a new way for fast functionalization of MOF and also provides a novel idea for material design in sample preparation, especially in glycoproteome and related analysis. 28537384 2 21 theme HeLa 556:559 arg1 lysate 566:571 HeLa cell lysate 556:571 HeLa cell lysate 556:571 Owing to the large specific surface area and ultrahigh hydrophilicity of this nanocomposite, excellent performance was observed in the enrichment of N-linked glycopeptides in both model glycoprotein and HeLa cell lysate. 28537384 0 22 theme Glycopeptides 108:120 arg1 Synthesis 56:64 Facile Synthesis 49:64 Facile Synthesis 49:64 Cysteine-Functionalized Metal-Organic Framework: Facile Synthesis and High Efficient Enrichment of N-Linked Glycopeptides in Cell Lysate. 28537384 0 22 theme Glycopeptides 108:120 arg1 Enrichment 85:94 High Efficient Enrichment 70:94 High Efficient Enrichment 70:94 Cysteine-Functionalized Metal-Organic Framework: Facile Synthesis and High Efficient Enrichment of N-Linked Glycopeptides in Cell Lysate. 28537384 4 23 theme serum 900:904 arg1 BSA 915:917 BSA 915:917 BSA 915:917 The short incubation time (5 min), large binding capacity (150 mg/g, IgG digest to material), good selectivity (1:50, molar ratio of IgG and bovine serum albumin (BSA) digest), high recovery (over 80%), and low detection limit (1 fmol) ensure the effectiveness and robustness of MIL-101(NH2)@Au-Cys in complex HeLa cell lysate. 28537384 4 23 theme serum 900:904 arg1 albumin 906:912 bovine serum albumin 893:912 bovine serum albumin (BSA) 893:918 The short incubation time (5 min), large binding capacity (150 mg/g, IgG digest to material), good selectivity (1:50, molar ratio of IgG and bovine serum albumin (BSA) digest), high recovery (over 80%), and low detection limit (1 fmol) ensure the effectiveness and robustness of MIL-101(NH2)@Au-Cys in complex HeLa cell lysate. 28537384 0 24 theme Cell 125:128 arg1 Lysate 130:135 Cell Lysate 125:135 Cell Lysate 125:135 Cysteine-Functionalized Metal-Organic Framework: Facile Synthesis and High Efficient Enrichment of N-Linked Glycopeptides in Cell Lysate. 28537384 2 25 gly glycoprotein 539:550 arg1 glycoprotein 539:550 model glycoprotein 533:550 model glycoprotein 533:550 Owing to the large specific surface area and ultrahigh hydrophilicity of this nanocomposite, excellent performance was observed in the enrichment of N-linked glycopeptides in both model glycoprotein and HeLa cell lysate. 28537384 2 26 from enrichment 488:497 arg1 glycoprotein 539:550 model glycoprotein 533:550 model glycoprotein 533:550 Owing to the large specific surface area and ultrahigh hydrophilicity of this nanocomposite, excellent performance was observed in the enrichment of N-linked glycopeptides in both model glycoprotein and HeLa cell lysate. 28537384 2 26 from enrichment 488:497 arg1 lysate 566:571 HeLa cell lysate 556:571 HeLa cell lysate 556:571 Owing to the large specific surface area and ultrahigh hydrophilicity of this nanocomposite, excellent performance was observed in the enrichment of N-linked glycopeptides in both model glycoprotein and HeLa cell lysate. 28537384 4 27 theme complex 1054:1060 arg1 lysate 1072:1077 complex HeLa cell lysate 1054:1077 complex HeLa cell lysate 1054:1077 The short incubation time (5 min), large binding capacity (150 mg/g, IgG digest to material), good selectivity (1:50, molar ratio of IgG and bovine serum albumin (BSA) digest), high recovery (over 80%), and low detection limit (1 fmol) ensure the effectiveness and robustness of MIL-101(NH2)@Au-Cys in complex HeLa cell lysate. 28537384 0 28 theme Cysteine-Functionalized 0:22 arg1 Framework 38:46 Cysteine-Functionalized Metal-Organic Framework 0:46 Cysteine-Functionalized Metal-Organic Framework 0:46 Cysteine-Functionalized Metal-Organic Framework: Facile Synthesis and High Efficient Enrichment of N-Linked Glycopeptides in Cell Lysate. 28537384 1 29 theme amino-derived 290:302 arg1 MOF 304:306 amino-derived MOF 290:306 amino-derived MOF followed by l-cysteine (Cys) immobilization 290:350 Cysteine-functionalized metal-organic framework (MOF) was synthesized via a common and facile two-step method of in situ loading of Au nanoparticles on amino-derived MOF followed by l-cysteine (Cys) immobilization. 28537384 4 30 theme cell 1067:1070 arg1 lysate 1072:1077 complex HeLa cell lysate 1054:1077 complex HeLa cell lysate 1054:1077 The short incubation time (5 min), large binding capacity (150 mg/g, IgG digest to material), good selectivity (1:50, molar ratio of IgG and bovine serum albumin (BSA) digest), high recovery (over 80%), and low detection limit (1 fmol) ensure the effectiveness and robustness of MIL-101(NH2)@Au-Cys in complex HeLa cell lysate. 28537384 4 31 theme short 756:760 arg1 time 773:776 The short incubation time 752:776 The short incubation time (5 min) 752:784 The short incubation time (5 min), large binding capacity (150 mg/g, IgG digest to material), good selectivity (1:50, molar ratio of IgG and bovine serum albumin (BSA) digest), high recovery (over 80%), and low detection limit (1 fmol) ensure the effectiveness and robustness of MIL-101(NH2)@Au-Cys in complex HeLa cell lysate. 28537384 4 31 theme short 756:760 arg1 min 781:783 5 min 779:783 5 min 779:783 The short incubation time (5 min), large binding capacity (150 mg/g, IgG digest to material), good selectivity (1:50, molar ratio of IgG and bovine serum albumin (BSA) digest), high recovery (over 80%), and low detection limit (1 fmol) ensure the effectiveness and robustness of MIL-101(NH2)@Au-Cys in complex HeLa cell lysate. 28537384 4 32 dep mg/g 815:818 arg1 digest 825:830 IgG digest 821:830 IgG digest to material 821:842 The short incubation time (5 min), large binding capacity (150 mg/g, IgG digest to material), good selectivity (1:50, molar ratio of IgG and bovine serum albumin (BSA) digest), high recovery (over 80%), and low detection limit (1 fmol) ensure the effectiveness and robustness of MIL-101(NH2)@Au-Cys in complex HeLa cell lysate. 28537384 7 33 theme MOF 1377:1379 arg1 functionalization 1356:1372 fast functionalization 1351:1372 fast functionalization of MOF 1351:1379 This work paves a new way for fast functionalization of MOF and also provides a novel idea for material design in sample preparation, especially in glycoproteome and related analysis. 28537384 2 34 gly glycopeptides 511:523 arg2 glycopeptides 511:523 N-linked glycopeptides 502:523 N-linked glycopeptides 502:523 Owing to the large specific surface area and ultrahigh hydrophilicity of this nanocomposite, excellent performance was observed in the enrichment of N-linked glycopeptides in both model glycoprotein and HeLa cell lysate. 28537384 7 35 theme related 1487:1493 arg1 analysis 1495:1502 related analysis 1487:1502 related analysis 1487:1502 This work paves a new way for fast functionalization of MOF and also provides a novel idea for material design in sample preparation, especially in glycoproteome and related analysis. 28537384 3 36 theme peroxidase 681:690 arg1 digest 659:664 digest 659:664 digest of horseradish peroxidase (HRP) and human serum immunoglobulin G (IgG), respectively 659:749 By using this nanocomposite, 16 and 31 glycopeptides were efficiently extracted from digest of horseradish peroxidase (HRP) and human serum immunoglobulin G (IgG), respectively. 28537384 0 37 theme Facile 49:54 arg1 Synthesis 56:64 Facile Synthesis 49:64 Facile Synthesis 49:64 Cysteine-Functionalized Metal-Organic Framework: Facile Synthesis and High Efficient Enrichment of N-Linked Glycopeptides in Cell Lysate. 28537384 1 38 theme l-cysteine 320:329 arg1 immobilization 337:350 l-cysteine (Cys) immobilization 320:350 l-cysteine (Cys) immobilization 320:350 Cysteine-functionalized metal-organic framework (MOF) was synthesized via a common and facile two-step method of in situ loading of Au nanoparticles on amino-derived MOF followed by l-cysteine (Cys) immobilization. 28537384 4 39 from Au-Cys 1044:1049 arg1 lysate 1072:1077 complex HeLa cell lysate 1054:1077 complex HeLa cell lysate 1054:1077 The short incubation time (5 min), large binding capacity (150 mg/g, IgG digest to material), good selectivity (1:50, molar ratio of IgG and bovine serum albumin (BSA) digest), high recovery (over 80%), and low detection limit (1 fmol) ensure the effectiveness and robustness of MIL-101(NH2)@Au-Cys in complex HeLa cell lysate. 28537384 4 40 theme high 929:932 arg1 % 951:951 over 80% 944:951 over 80% 944:951 The short incubation time (5 min), large binding capacity (150 mg/g, IgG digest to material), good selectivity (1:50, molar ratio of IgG and bovine serum albumin (BSA) digest), high recovery (over 80%), and low detection limit (1 fmol) ensure the effectiveness and robustness of MIL-101(NH2)@Au-Cys in complex HeLa cell lysate. 28537384 4 40 theme high 929:932 arg1 recovery 934:941 high recovery 929:941 high recovery (over 80%) 929:952 The short incubation time (5 min), large binding capacity (150 mg/g, IgG digest to material), good selectivity (1:50, molar ratio of IgG and bovine serum albumin (BSA) digest), high recovery (over 80%), and low detection limit (1 fmol) ensure the effectiveness and robustness of MIL-101(NH2)@Au-Cys in complex HeLa cell lysate. 28537384 6 41 theme reported 1249:1256 arg1 methods 1270:1276 previously reported hydrophilic methods 1238:1276 previously reported hydrophilic methods 1238:1276 Compared with those of previously reported hydrophilic methods, to our knowledge, it was the best result. 28537384 1 42 theme Cys 332:334 arg1 immobilization 337:350 l-cysteine (Cys) immobilization 320:350 l-cysteine (Cys) immobilization 320:350 Cysteine-functionalized metal-organic framework (MOF) was synthesized via a common and facile two-step method of in situ loading of Au nanoparticles on amino-derived MOF followed by l-cysteine (Cys) immobilization. 28537384 4 43 theme detection 963:971 arg1 limit 973:977 low detection limit 959:977 low detection limit (1 fmol) 959:986 The short incubation time (5 min), large binding capacity (150 mg/g, IgG digest to material), good selectivity (1:50, molar ratio of IgG and bovine serum albumin (BSA) digest), high recovery (over 80%), and low detection limit (1 fmol) ensure the effectiveness and robustness of MIL-101(NH2)@Au-Cys in complex HeLa cell lysate. 28537384 4 43 theme detection 963:971 arg1 fmol 982:985 1 fmol 980:985 1 fmol 980:985 The short incubation time (5 min), large binding capacity (150 mg/g, IgG digest to material), good selectivity (1:50, molar ratio of IgG and bovine serum albumin (BSA) digest), high recovery (over 80%), and low detection limit (1 fmol) ensure the effectiveness and robustness of MIL-101(NH2)@Au-Cys in complex HeLa cell lysate. 28537384 7 44 theme new 1339:1341 arg1 way 1343:1345 a new way 1337:1345 a new way for fast functionalization of MOF 1337:1379 This work paves a new way for fast functionalization of MOF and also provides a novel idea for material design in sample preparation, especially in glycoproteome and related analysis. 28537384 6 45 theme hydrophilic 1258:1268 arg1 methods 1270:1276 previously reported hydrophilic methods 1238:1276 previously reported hydrophilic methods 1238:1276 Compared with those of previously reported hydrophilic methods, to our knowledge, it was the best result. 28537384 5 46 gly N-glycosylation 1098:1112 arg2 result 1085:1090 a result 1083:1090 a result 1083:1090 As a result, 1123 N-glycosylation sites corresponding to 1069 N-glycopeptides and 614 N-glycoproteins were identified from the lysate. 28537384 5 46 gly N-glycosylation 1098:1112 arg2 sites 1114:1118 1123 N-glycosylation sites 1093:1118 1123 N-glycosylation sites corresponding to 1069 N-glycopeptides and 614 N-glycoproteins 1093:1180 As a result, 1123 N-glycosylation sites corresponding to 1069 N-glycopeptides and 614 N-glycoproteins were identified from the lysate. 28537384 4 47 theme large 787:791 arg1 capacity 801:808 large binding capacity 787:808 large binding capacity (150 mg/g, IgG digest to material) 787:843 The short incubation time (5 min), large binding capacity (150 mg/g, IgG digest to material), good selectivity (1:50, molar ratio of IgG and bovine serum albumin (BSA) digest), high recovery (over 80%), and low detection limit (1 fmol) ensure the effectiveness and robustness of MIL-101(NH2)@Au-Cys in complex HeLa cell lysate. 28537384 2 48 theme surface 381:387 arg1 area 389:392 the large specific surface area 362:392 the large specific surface area 362:392 Owing to the large specific surface area and ultrahigh hydrophilicity of this nanocomposite, excellent performance was observed in the enrichment of N-linked glycopeptides in both model glycoprotein and HeLa cell lysate. 28537384 4 49 dep selectivity 851:861 arg1 1:50 864:867 1:50 864:867 1:50 864:867 The short incubation time (5 min), large binding capacity (150 mg/g, IgG digest to material), good selectivity (1:50, molar ratio of IgG and bovine serum albumin (BSA) digest), high recovery (over 80%), and low detection limit (1 fmol) ensure the effectiveness and robustness of MIL-101(NH2)@Au-Cys in complex HeLa cell lysate. 28537384 2 50 theme large 366:370 arg1 area 389:392 the large specific surface area 362:392 the large specific surface area 362:392 Owing to the large specific surface area and ultrahigh hydrophilicity of this nanocomposite, excellent performance was observed in the enrichment of N-linked glycopeptides in both model glycoprotein and HeLa cell lysate. 28537384 3 51 theme serum 708:712 arg1 IgG 732:734 IgG 732:734 IgG 732:734 By using this nanocomposite, 16 and 31 glycopeptides were efficiently extracted from digest of horseradish peroxidase (HRP) and human serum immunoglobulin G (IgG), respectively. 28537384 3 51 theme serum 708:712 arg1 G 729:729 human serum immunoglobulin G 702:729 human serum immunoglobulin G (IgG) 702:735 By using this nanocomposite, 16 and 31 glycopeptides were efficiently extracted from digest of horseradish peroxidase (HRP) and human serum immunoglobulin G (IgG), respectively. 28537384 1 52 theme nanoparticles 273:285 arg1 loading 259:265 in situ loading 251:265 in situ loading of Au nanoparticles on amino-derived MOF followed by l-cysteine (Cys) immobilization 251:350 Cysteine-functionalized metal-organic framework (MOF) was synthesized via a common and facile two-step method of in situ loading of Au nanoparticles on amino-derived MOF followed by l-cysteine (Cys) immobilization. 28537384 4 53 from robustness 1017:1026 arg1 lysate 1072:1077 complex HeLa cell lysate 1054:1077 complex HeLa cell lysate 1054:1077 The short incubation time (5 min), large binding capacity (150 mg/g, IgG digest to material), good selectivity (1:50, molar ratio of IgG and bovine serum albumin (BSA) digest), high recovery (over 80%), and low detection limit (1 fmol) ensure the effectiveness and robustness of MIL-101(NH2)@Au-Cys in complex HeLa cell lysate. 28537384 5 54 gly N-glycoproteins 1166:1180 arg1 N-glycoproteins 1166:1180 614 N-glycoproteins 1162:1180 614 N-glycoproteins 1162:1180 As a result, 1123 N-glycosylation sites corresponding to 1069 N-glycopeptides and 614 N-glycoproteins were identified from the lysate. 28537384 4 55 from effectiveness 999:1011 arg1 lysate 1072:1077 complex HeLa cell lysate 1054:1077 complex HeLa cell lysate 1054:1077 The short incubation time (5 min), large binding capacity (150 mg/g, IgG digest to material), good selectivity (1:50, molar ratio of IgG and bovine serum albumin (BSA) digest), high recovery (over 80%), and low detection limit (1 fmol) ensure the effectiveness and robustness of MIL-101(NH2)@Au-Cys in complex HeLa cell lysate. 28537384 4 56 theme IgG 821:823 arg1 digest 825:830 IgG digest 821:830 IgG digest to material 821:842 The short incubation time (5 min), large binding capacity (150 mg/g, IgG digest to material), good selectivity (1:50, molar ratio of IgG and bovine serum albumin (BSA) digest), high recovery (over 80%), and low detection limit (1 fmol) ensure the effectiveness and robustness of MIL-101(NH2)@Au-Cys in complex HeLa cell lysate. 28537384 1 57 theme two-step 232:239 arg1 method 241:246 a common and facile two-step method 212:246 a common and facile two-step method of in situ loading of Au nanoparticles on amino-derived MOF followed by l-cysteine (Cys) immobilization 212:350 Cysteine-functionalized metal-organic framework (MOF) was synthesized via a common and facile two-step method of in situ loading of Au nanoparticles on amino-derived MOF followed by l-cysteine (Cys) immobilization. 28537384 2 58 theme cell 561:564 arg1 lysate 566:571 HeLa cell lysate 556:571 HeLa cell lysate 556:571 Owing to the large specific surface area and ultrahigh hydrophilicity of this nanocomposite, excellent performance was observed in the enrichment of N-linked glycopeptides in both model glycoprotein and HeLa cell lysate. 28537384 0 59 from Enrichment 85:94 arg1 Lysate 130:135 Cell Lysate 125:135 Cell Lysate 125:135 Cysteine-Functionalized Metal-Organic Framework: Facile Synthesis and High Efficient Enrichment of N-Linked Glycopeptides in Cell Lysate. 28537384 4 60 theme @ 1043:1043 arg1 Au-Cys 1044:1049 MIL-101(NH2)@Au-Cys 1031:1049 MIL-101(NH2)@Au-Cys in complex HeLa cell lysate 1031:1077 The short incubation time (5 min), large binding capacity (150 mg/g, IgG digest to material), good selectivity (1:50, molar ratio of IgG and bovine serum albumin (BSA) digest), high recovery (over 80%), and low detection limit (1 fmol) ensure the effectiveness and robustness of MIL-101(NH2)@Au-Cys in complex HeLa cell lysate. 28537384 1 61 from method 241:246 arg1 MOF 304:306 amino-derived MOF 290:306 amino-derived MOF followed by l-cysteine (Cys) immobilization 290:350 Cysteine-functionalized metal-organic framework (MOF) was synthesized via a common and facile two-step method of in situ loading of Au nanoparticles on amino-derived MOF followed by l-cysteine (Cys) immobilization. 28537384 4 62 theme good 846:849 arg1 selectivity 851:861 good selectivity 846:861 good selectivity (1:50, molar ratio of IgG and bovine serum albumin (BSA) digest) 846:926 The short incubation time (5 min), large binding capacity (150 mg/g, IgG digest to material), good selectivity (1:50, molar ratio of IgG and bovine serum albumin (BSA) digest), high recovery (over 80%), and low detection limit (1 fmol) ensure the effectiveness and robustness of MIL-101(NH2)@Au-Cys in complex HeLa cell lysate. 28537384 1 63 theme metal-organic 162:174 arg1 MOF 187:189 MOF 187:189 MOF 187:189 Cysteine-functionalized metal-organic framework (MOF) was synthesized via a common and facile two-step method of in situ loading of Au nanoparticles on amino-derived MOF followed by l-cysteine (Cys) immobilization. 28537384 1 63 theme metal-organic 162:174 arg1 framework 176:184 Cysteine-functionalized metal-organic framework 138:184 Cysteine-functionalized metal-organic framework (MOF) 138:190 Cysteine-functionalized metal-organic framework (MOF) was synthesized via a common and facile two-step method of in situ loading of Au nanoparticles on amino-derived MOF followed by l-cysteine (Cys) immobilization. 28537384 7 64 theme material 1416:1423 arg1 design 1425:1430 material design 1416:1430 material design 1416:1430 This work paves a new way for fast functionalization of MOF and also provides a novel idea for material design in sample preparation, especially in glycoproteome and related analysis. 28537384 4 65 theme MIL-101 1031:1037 arg1 Au-Cys 1044:1049 MIL-101(NH2)@Au-Cys 1031:1049 MIL-101(NH2)@Au-Cys in complex HeLa cell lysate 1031:1077 The short incubation time (5 min), large binding capacity (150 mg/g, IgG digest to material), good selectivity (1:50, molar ratio of IgG and bovine serum albumin (BSA) digest), high recovery (over 80%), and low detection limit (1 fmol) ensure the effectiveness and robustness of MIL-101(NH2)@Au-Cys in complex HeLa cell lysate. 28537384 4 66 dep 1:50 864:867 arg1 ratio 876:880 molar ratio 870:880 molar ratio of IgG and bovine serum albumin (BSA) digest 870:925 The short incubation time (5 min), large binding capacity (150 mg/g, IgG digest to material), good selectivity (1:50, molar ratio of IgG and bovine serum albumin (BSA) digest), high recovery (over 80%), and low detection limit (1 fmol) ensure the effectiveness and robustness of MIL-101(NH2)@Au-Cys in complex HeLa cell lysate. 28537384 4 67 theme albumin 906:912 arg1 ratio 876:880 molar ratio 870:880 molar ratio of IgG and bovine serum albumin (BSA) digest 870:925 The short incubation time (5 min), large binding capacity (150 mg/g, IgG digest to material), good selectivity (1:50, molar ratio of IgG and bovine serum albumin (BSA) digest), high recovery (over 80%), and low detection limit (1 fmol) ensure the effectiveness and robustness of MIL-101(NH2)@Au-Cys in complex HeLa cell lysate. 28537384 4 68 theme NH2 1039:1041 arg1 Au-Cys 1044:1049 MIL-101(NH2)@Au-Cys 1031:1049 MIL-101(NH2)@Au-Cys in complex HeLa cell lysate 1031:1077 The short incubation time (5 min), large binding capacity (150 mg/g, IgG digest to material), good selectivity (1:50, molar ratio of IgG and bovine serum albumin (BSA) digest), high recovery (over 80%), and low detection limit (1 fmol) ensure the effectiveness and robustness of MIL-101(NH2)@Au-Cys in complex HeLa cell lysate. 28537384 0 69 theme N-Linked 99:106 arg1 Glycopeptides 108:120 N-Linked Glycopeptides 99:120 N-Linked Glycopeptides 99:120 Cysteine-Functionalized Metal-Organic Framework: Facile Synthesis and High Efficient Enrichment of N-Linked Glycopeptides in Cell Lysate. 28537384 2 70 theme N-linked 502:509 arg1 glycopeptides 511:523 N-linked glycopeptides 502:523 N-linked glycopeptides 502:523 Owing to the large specific surface area and ultrahigh hydrophilicity of this nanocomposite, excellent performance was observed in the enrichment of N-linked glycopeptides in both model glycoprotein and HeLa cell lysate. 28537384 5 71 theme N-glycosylation 1098:1112 arg1 sites 1114:1118 1123 N-glycosylation sites 1093:1118 1123 N-glycosylation sites corresponding to 1069 N-glycopeptides and 614 N-glycoproteins 1093:1180 As a result, 1123 N-glycosylation sites corresponding to 1069 N-glycopeptides and 614 N-glycoproteins were identified from the lysate. 28537384 5 71 theme N-glycosylation 1098:1112 arg1 result 1085:1090 a result 1083:1090 a result 1083:1090 As a result, 1123 N-glycosylation sites corresponding to 1069 N-glycopeptides and 614 N-glycoproteins were identified from the lysate. 28537384 4 72 theme IgG 885:887 arg1 ratio 876:880 molar ratio 870:880 molar ratio of IgG and bovine serum albumin (BSA) digest 870:925 The short incubation time (5 min), large binding capacity (150 mg/g, IgG digest to material), good selectivity (1:50, molar ratio of IgG and bovine serum albumin (BSA) digest), high recovery (over 80%), and low detection limit (1 fmol) ensure the effectiveness and robustness of MIL-101(NH2)@Au-Cys in complex HeLa cell lysate. 28537384 4 73 theme incubation 762:771 arg1 time 773:776 The short incubation time 752:776 The short incubation time (5 min) 752:784 The short incubation time (5 min), large binding capacity (150 mg/g, IgG digest to material), good selectivity (1:50, molar ratio of IgG and bovine serum albumin (BSA) digest), high recovery (over 80%), and low detection limit (1 fmol) ensure the effectiveness and robustness of MIL-101(NH2)@Au-Cys in complex HeLa cell lysate. 28537384 4 73 theme incubation 762:771 arg1 min 781:783 5 min 779:783 5 min 779:783 The short incubation time (5 min), large binding capacity (150 mg/g, IgG digest to material), good selectivity (1:50, molar ratio of IgG and bovine serum albumin (BSA) digest), high recovery (over 80%), and low detection limit (1 fmol) ensure the effectiveness and robustness of MIL-101(NH2)@Au-Cys in complex HeLa cell lysate. 28537384 4 74 theme bovine 893:898 arg1 BSA 915:917 BSA 915:917 BSA 915:917 The short incubation time (5 min), large binding capacity (150 mg/g, IgG digest to material), good selectivity (1:50, molar ratio of IgG and bovine serum albumin (BSA) digest), high recovery (over 80%), and low detection limit (1 fmol) ensure the effectiveness and robustness of MIL-101(NH2)@Au-Cys in complex HeLa cell lysate. 28537384 4 74 theme bovine 893:898 arg1 albumin 906:912 bovine serum albumin 893:912 bovine serum albumin (BSA) 893:918 The short incubation time (5 min), large binding capacity (150 mg/g, IgG digest to material), good selectivity (1:50, molar ratio of IgG and bovine serum albumin (BSA) digest), high recovery (over 80%), and low detection limit (1 fmol) ensure the effectiveness and robustness of MIL-101(NH2)@Au-Cys in complex HeLa cell lysate. 28537384 0 75 from Synthesis 56:64 arg1 Lysate 130:135 Cell Lysate 125:135 Cell Lysate 125:135 Cysteine-Functionalized Metal-Organic Framework: Facile Synthesis and High Efficient Enrichment of N-Linked Glycopeptides in Cell Lysate. 28537384 4 76 theme HeLa 1062:1065 arg1 lysate 1072:1077 complex HeLa cell lysate 1054:1077 complex HeLa cell lysate 1054:1077 The short incubation time (5 min), large binding capacity (150 mg/g, IgG digest to material), good selectivity (1:50, molar ratio of IgG and bovine serum albumin (BSA) digest), high recovery (over 80%), and low detection limit (1 fmol) ensure the effectiveness and robustness of MIL-101(NH2)@Au-Cys in complex HeLa cell lysate. 28537384 2 77 theme ultrahigh 398:406 arg1 hydrophilicity 408:421 ultrahigh hydrophilicity 398:421 ultrahigh hydrophilicity of this nanocomposite 398:443 Owing to the large specific surface area and ultrahigh hydrophilicity of this nanocomposite, excellent performance was observed in the enrichment of N-linked glycopeptides in both model glycoprotein and HeLa cell lysate. 28537384 0 78 theme Metal-Organic 24:36 arg1 Framework 38:46 Cysteine-Functionalized Metal-Organic Framework 0:46 Cysteine-Functionalized Metal-Organic Framework 0:46 Cysteine-Functionalized Metal-Organic Framework: Facile Synthesis and High Efficient Enrichment of N-Linked Glycopeptides in Cell Lysate. 28537384 4 79 from lysate 1072:1077 arg1 effectiveness 999:1011 the effectiveness 995:1011 the effectiveness 995:1011 The short incubation time (5 min), large binding capacity (150 mg/g, IgG digest to material), good selectivity (1:50, molar ratio of IgG and bovine serum albumin (BSA) digest), high recovery (over 80%), and low detection limit (1 fmol) ensure the effectiveness and robustness of MIL-101(NH2)@Au-Cys in complex HeLa cell lysate. 28537384 4 79 from lysate 1072:1077 arg1 robustness 1017:1026 robustness 1017:1026 robustness 1017:1026 The short incubation time (5 min), large binding capacity (150 mg/g, IgG digest to material), good selectivity (1:50, molar ratio of IgG and bovine serum albumin (BSA) digest), high recovery (over 80%), and low detection limit (1 fmol) ensure the effectiveness and robustness of MIL-101(NH2)@Au-Cys in complex HeLa cell lysate. 28537384 2 80 theme excellent 446:454 arg1 performance 456:466 excellent performance 446:466 excellent performance 446:466 Owing to the large specific surface area and ultrahigh hydrophilicity of this nanocomposite, excellent performance was observed in the enrichment of N-linked glycopeptides in both model glycoprotein and HeLa cell lysate. 28537384 3 81 theme horseradish 669:679 arg1 HRP 693:695 HRP 693:695 HRP 693:695 By using this nanocomposite, 16 and 31 glycopeptides were efficiently extracted from digest of horseradish peroxidase (HRP) and human serum immunoglobulin G (IgG), respectively. 28537384 3 81 theme horseradish 669:679 arg1 peroxidase 681:690 horseradish peroxidase 669:690 horseradish peroxidase (HRP) 669:696 By using this nanocomposite, 16 and 31 glycopeptides were efficiently extracted from digest of horseradish peroxidase (HRP) and human serum immunoglobulin G (IgG), respectively. 28537384 2 82 theme nanocomposite 431:443 arg1 area 389:392 the large specific surface area 362:392 the large specific surface area 362:392 Owing to the large specific surface area and ultrahigh hydrophilicity of this nanocomposite, excellent performance was observed in the enrichment of N-linked glycopeptides in both model glycoprotein and HeLa cell lysate. 28537384 2 82 theme nanocomposite 431:443 arg1 hydrophilicity 408:421 ultrahigh hydrophilicity 398:421 ultrahigh hydrophilicity of this nanocomposite 398:443 Owing to the large specific surface area and ultrahigh hydrophilicity of this nanocomposite, excellent performance was observed in the enrichment of N-linked glycopeptides in both model glycoprotein and HeLa cell lysate. 28537384 4 83 dep capacity 801:808 arg1 mg/g 815:818 150 mg/g 811:818 150 mg/g 811:818 The short incubation time (5 min), large binding capacity (150 mg/g, IgG digest to material), good selectivity (1:50, molar ratio of IgG and bovine serum albumin (BSA) digest), high recovery (over 80%), and low detection limit (1 fmol) ensure the effectiveness and robustness of MIL-101(NH2)@Au-Cys in complex HeLa cell lysate. 28537384 5 84 gly N-glycopeptides 1142:1156 arg2 N-glycopeptides 1142:1156 1069 N-glycopeptides 1137:1156 1069 N-glycopeptides 1137:1156 As a result, 1123 N-glycosylation sites corresponding to 1069 N-glycopeptides and 614 N-glycoproteins were identified from the lysate. 28537384 4 85 theme binding 793:799 arg1 capacity 801:808 large binding capacity 787:808 large binding capacity (150 mg/g, IgG digest to material) 787:843 The short incubation time (5 min), large binding capacity (150 mg/g, IgG digest to material), good selectivity (1:50, molar ratio of IgG and bovine serum albumin (BSA) digest), high recovery (over 80%), and low detection limit (1 fmol) ensure the effectiveness and robustness of MIL-101(NH2)@Au-Cys in complex HeLa cell lysate. 28537384 2 86 theme model 533:537 arg1 glycoprotein 539:550 model glycoprotein 533:550 model glycoprotein 533:550 Owing to the large specific surface area and ultrahigh hydrophilicity of this nanocomposite, excellent performance was observed in the enrichment of N-linked glycopeptides in both model glycoprotein and HeLa cell lysate. 28537384 0 87 theme High 70:73 arg1 Enrichment 85:94 High Efficient Enrichment 70:94 High Efficient Enrichment 70:94 Cysteine-Functionalized Metal-Organic Framework: Facile Synthesis and High Efficient Enrichment of N-Linked Glycopeptides in Cell Lysate. 28537384 0 88 dep Synthesis 56:64 arg1 Framework 38:46 Cysteine-Functionalized Metal-Organic Framework 0:46 Cysteine-Functionalized Metal-Organic Framework 0:46 Cysteine-Functionalized Metal-Organic Framework: Facile Synthesis and High Efficient Enrichment of N-Linked Glycopeptides in Cell Lysate. 28537384 7 89 theme fast 1351:1354 arg1 functionalization 1356:1372 fast functionalization 1351:1372 fast functionalization of MOF 1351:1379 This work paves a new way for fast functionalization of MOF and also provides a novel idea for material design in sample preparation, especially in glycoproteome and related analysis. 28537384 4 90 theme low 959:961 arg1 limit 973:977 low detection limit 959:977 low detection limit (1 fmol) 959:986 The short incubation time (5 min), large binding capacity (150 mg/g, IgG digest to material), good selectivity (1:50, molar ratio of IgG and bovine serum albumin (BSA) digest), high recovery (over 80%), and low detection limit (1 fmol) ensure the effectiveness and robustness of MIL-101(NH2)@Au-Cys in complex HeLa cell lysate. 28537384 4 90 theme low 959:961 arg1 fmol 982:985 1 fmol 980:985 1 fmol 980:985 The short incubation time (5 min), large binding capacity (150 mg/g, IgG digest to material), good selectivity (1:50, molar ratio of IgG and bovine serum albumin (BSA) digest), high recovery (over 80%), and low detection limit (1 fmol) ensure the effectiveness and robustness of MIL-101(NH2)@Au-Cys in complex HeLa cell lysate. 28537384 1 91 theme in 251:252 arg1 loading 259:265 in situ loading 251:265 in situ loading of Au nanoparticles on amino-derived MOF followed by l-cysteine (Cys) immobilization 251:350 Cysteine-functionalized metal-organic framework (MOF) was synthesized via a common and facile two-step method of in situ loading of Au nanoparticles on amino-derived MOF followed by l-cysteine (Cys) immobilization. 28537384 3 92 theme immunoglobulin 714:727 arg1 IgG 732:734 IgG 732:734 IgG 732:734 By using this nanocomposite, 16 and 31 glycopeptides were efficiently extracted from digest of horseradish peroxidase (HRP) and human serum immunoglobulin G (IgG), respectively. 28537384 3 92 theme immunoglobulin 714:727 arg1 G 729:729 human serum immunoglobulin G 702:729 human serum immunoglobulin G (IgG) 702:735 By using this nanocomposite, 16 and 31 glycopeptides were efficiently extracted from digest of horseradish peroxidase (HRP) and human serum immunoglobulin G (IgG), respectively. 28537384 1 93 link amino-derived 290:302 arg1 MOF 304:306 amino-derived MOF 290:306 amino-derived MOF followed by l-cysteine (Cys) immobilization 290:350 Cysteine-functionalized metal-organic framework (MOF) was synthesized via a common and facile two-step method of in situ loading of Au nanoparticles on amino-derived MOF followed by l-cysteine (Cys) immobilization. 28537384 2 94 theme specific 372:379 arg1 area 389:392 the large specific surface area 362:392 the large specific surface area 362:392 Owing to the large specific surface area and ultrahigh hydrophilicity of this nanocomposite, excellent performance was observed in the enrichment of N-linked glycopeptides in both model glycoprotein and HeLa cell lysate. 28537384 1 95 theme loading 259:265 arg1 method 241:246 a common and facile two-step method 212:246 a common and facile two-step method of in situ loading of Au nanoparticles on amino-derived MOF followed by l-cysteine (Cys) immobilization 212:350 Cysteine-functionalized metal-organic framework (MOF) was synthesized via a common and facile two-step method of in situ loading of Au nanoparticles on amino-derived MOF followed by l-cysteine (Cys) immobilization. 25344606 8 0 theme ST6GAL1 1119:1125 arg1 knockdown 1127:1135 ST6GAL1 knockdown 1119:1135 ST6GAL1 knockdown 1119:1135 Moreover, ST6GAL1 knockdown inhibited the phosphorylation of Akt, but not Smad2, suggesting that ST6GAL1 contributes to EMT through a non-Smad signaling pathway. 25344606 4 1 theme St6gal1 586:592 arg1 Knockdown 573:581 Knockdown 573:581 Knockdown of St6gal1 573:592 Knockdown of St6gal1 strongly suppressed TGF-β-induced EMT with a concomitant increase in E-cadherin expression, a major determinant of epithelial cell adherens junctions. 25344606 8 2 theme non-Smad 1243:1250 arg1 pathway 1262:1268 a non-Smad signaling pathway 1241:1268 a non-Smad signaling pathway 1241:1268 Moreover, ST6GAL1 knockdown inhibited the phosphorylation of Akt, but not Smad2, suggesting that ST6GAL1 contributes to EMT through a non-Smad signaling pathway. 25344606 7 3 theme cells 1058:1062 arg1 phenotype 1014:1022 The basal mesenchymal phenotype 992:1022 The basal mesenchymal phenotype of MDA-MB-231 human breast cancer cells 992:1062 The basal mesenchymal phenotype of MDA-MB-231 human breast cancer cells was partially reversed by ST6GAL1 silencing. 25344606 9 4 theme up-regulated 1456:1467 arg1 ST6GAL1 1469:1475 up-regulated ST6GAL1 1456:1475 up-regulated ST6GAL1 1456:1475 Taken together, our data indicate that ST6GAL1 promotes TGF-β-dependent EMT as well as maintenance of the mesenchymal state by growth signaling, providing a plausible mechanism whereby up-regulated ST6GAL1 may promote malignant progression. 25344606 4 5 theme TGF-β-induced 614:626 arg1 EMT 628:630 TGF-β-induced EMT 614:630 TGF-β-induced EMT 614:630 Knockdown of St6gal1 strongly suppressed TGF-β-induced EMT with a concomitant increase in E-cadherin expression, a major determinant of epithelial cell adherens junctions. 25344606 9 6 theme mesenchymal 1377:1387 arg1 state 1389:1393 the mesenchymal state 1373:1393 the mesenchymal state 1373:1393 Taken together, our data indicate that ST6GAL1 promotes TGF-β-dependent EMT as well as maintenance of the mesenchymal state by growth signaling, providing a plausible mechanism whereby up-regulated ST6GAL1 may promote malignant progression. 25344606 7 7 theme human 1038:1042 arg1 cells 1058:1062 MDA-MB-231 human breast cancer cells 1027:1062 MDA-MB-231 human breast cancer cells 1027:1062 The basal mesenchymal phenotype of MDA-MB-231 human breast cancer cells was partially reversed by ST6GAL1 silencing. 25344606 5 8 theme TGF-β-induced 846:858 arg1 EMT 860:862 TGF-β-induced EMT 846:862 TGF-β-induced EMT 846:862 Conversely, overexpression of ST6GAL1 increased the turnover of cell surface E-cadherin and promoted TGF-β-induced EMT. 25344606 5 9 theme ST6GAL1 775:781 arg1 overexpression 757:770 overexpression 757:770 overexpression of ST6GAL1 757:781 Conversely, overexpression of ST6GAL1 increased the turnover of cell surface E-cadherin and promoted TGF-β-induced EMT. 25344606 7 10 theme breast 1044:1049 arg1 cells 1058:1062 MDA-MB-231 human breast cancer cells 1027:1062 MDA-MB-231 human breast cancer cells 1027:1062 The basal mesenchymal phenotype of MDA-MB-231 human breast cancer cells was partially reversed by ST6GAL1 silencing. 25344606 3 11 theme TGF-β-induced 449:461 arg1 EMT 498:500 EMT 498:500 EMT 498:500 Here, we report that St6gal1 transcription and α2,6-sialylated N-glycans are up-regulated during TGF-β-induced epithelial-mesenchymal transition (EMT) in GE11 cells, requiring the Sp1 element within the St6gal1 promoter. 25344606 3 11 theme TGF-β-induced 449:461 arg1 transition 486:495 TGF-β-induced epithelial-mesenchymal transition 449:495 TGF-β-induced epithelial-mesenchymal transition (EMT) in GE11 cells 449:515 Here, we report that St6gal1 transcription and α2,6-sialylated N-glycans are up-regulated during TGF-β-induced epithelial-mesenchymal transition (EMT) in GE11 cells, requiring the Sp1 element within the St6gal1 promoter. 25344606 8 12 theme Akt 1170:1172 arg1 phosphorylation 1151:1165 the phosphorylation 1147:1165 the phosphorylation of Akt, but not Smad2 1147:1187 Moreover, ST6GAL1 knockdown inhibited the phosphorylation of Akt, but not Smad2, suggesting that ST6GAL1 contributes to EMT through a non-Smad signaling pathway. 25344606 4 13 theme major 688:692 arg1 determinant 694:704 a major determinant 686:704 a major determinant of epithelial cell adherens junctions 686:742 Knockdown of St6gal1 strongly suppressed TGF-β-induced EMT with a concomitant increase in E-cadherin expression, a major determinant of epithelial cell adherens junctions. 25344606 4 13 theme major 688:692 arg1 expression 674:683 E-cadherin expression 663:683 E-cadherin expression 663:683 Knockdown of St6gal1 strongly suppressed TGF-β-induced EMT with a concomitant increase in E-cadherin expression, a major determinant of epithelial cell adherens junctions. 25344606 3 14 from transition 486:495 arg1 cells 511:515 GE11 cells 506:515 GE11 cells 506:515 Here, we report that St6gal1 transcription and α2,6-sialylated N-glycans are up-regulated during TGF-β-induced epithelial-mesenchymal transition (EMT) in GE11 cells, requiring the Sp1 element within the St6gal1 promoter. 25344606 4 15 theme junctions 734:742 arg1 determinant 694:704 a major determinant 686:704 a major determinant of epithelial cell adherens junctions 686:742 Knockdown of St6gal1 strongly suppressed TGF-β-induced EMT with a concomitant increase in E-cadherin expression, a major determinant of epithelial cell adherens junctions. 25344606 4 15 theme junctions 734:742 arg1 expression 674:683 E-cadherin expression 663:683 E-cadherin expression 663:683 Knockdown of St6gal1 strongly suppressed TGF-β-induced EMT with a concomitant increase in E-cadherin expression, a major determinant of epithelial cell adherens junctions. 25344606 1 16 theme β-Galactoside 120:132 arg1 α2,6-sialyltranferase 134:154 β-Galactoside α2,6-sialyltranferase 1 120:156 β-Galactoside α2,6-sialyltranferase 1 (ST6GAL1) 120:166 β-Galactoside α2,6-sialyltranferase 1 (ST6GAL1) catalyzes the addition of terminal α2,6-sialylation to N-glycans. 25344606 1 16 theme β-Galactoside 120:132 arg1 ST6GAL1 159:165 ST6GAL1 159:165 ST6GAL1 159:165 β-Galactoside α2,6-sialyltranferase 1 (ST6GAL1) catalyzes the addition of terminal α2,6-sialylation to N-glycans. 25344606 7 17 theme MDA-MB-231 1027:1036 arg1 cells 1058:1062 MDA-MB-231 human breast cancer cells 1027:1062 MDA-MB-231 human breast cancer cells 1027:1062 The basal mesenchymal phenotype of MDA-MB-231 human breast cancer cells was partially reversed by ST6GAL1 silencing. 25344606 3 18 theme GE11 506:509 arg1 cells 511:515 GE11 cells 506:515 GE11 cells 506:515 Here, we report that St6gal1 transcription and α2,6-sialylated N-glycans are up-regulated during TGF-β-induced epithelial-mesenchymal transition (EMT) in GE11 cells, requiring the Sp1 element within the St6gal1 promoter. 25344606 7 19 theme mesenchymal 1002:1012 arg1 phenotype 1014:1022 The basal mesenchymal phenotype 992:1022 The basal mesenchymal phenotype of MDA-MB-231 human breast cancer cells 992:1062 The basal mesenchymal phenotype of MDA-MB-231 human breast cancer cells was partially reversed by ST6GAL1 silencing. 25344606 3 20 theme Sp1 532:534 arg1 element 536:542 the Sp1 element 528:542 the Sp1 element within the St6gal1 promoter 528:570 Here, we report that St6gal1 transcription and α2,6-sialylated N-glycans are up-regulated during TGF-β-induced epithelial-mesenchymal transition (EMT) in GE11 cells, requiring the Sp1 element within the St6gal1 promoter. 25344606 3 21 theme St6gal1 373:379 arg1 transcription 381:393 St6gal1 transcription 373:393 St6gal1 transcription 373:393 Here, we report that St6gal1 transcription and α2,6-sialylated N-glycans are up-regulated during TGF-β-induced epithelial-mesenchymal transition (EMT) in GE11 cells, requiring the Sp1 element within the St6gal1 promoter. 25344606 0 22 theme β-Galactoside 0:12 arg1 α2,6-sialyltranferase 14:34 β-Galactoside α2,6-sialyltranferase 1 0:36 β-Galactoside α2,6-sialyltranferase 1 0:36 β-Galactoside α2,6-sialyltranferase 1 promotes transforming growth factor-β-mediated epithelial-mesenchymal transition. 25344606 7 23 theme ST6GAL1 1090:1096 arg1 silencing 1098:1106 ST6GAL1 silencing 1090:1106 ST6GAL1 silencing 1090:1106 The basal mesenchymal phenotype of MDA-MB-231 human breast cancer cells was partially reversed by ST6GAL1 silencing. 25344606 3 24 theme epithelial-mesenchymal 463:484 arg1 EMT 498:500 EMT 498:500 EMT 498:500 Here, we report that St6gal1 transcription and α2,6-sialylated N-glycans are up-regulated during TGF-β-induced epithelial-mesenchymal transition (EMT) in GE11 cells, requiring the Sp1 element within the St6gal1 promoter. 25344606 3 24 theme epithelial-mesenchymal 463:484 arg1 transition 486:495 TGF-β-induced epithelial-mesenchymal transition 449:495 TGF-β-induced epithelial-mesenchymal transition (EMT) in GE11 cells 449:515 Here, we report that St6gal1 transcription and α2,6-sialylated N-glycans are up-regulated during TGF-β-induced epithelial-mesenchymal transition (EMT) in GE11 cells, requiring the Sp1 element within the St6gal1 promoter. 25344606 8 25 theme Smad2 1183:1187 arg1 phosphorylation 1151:1165 the phosphorylation 1147:1165 the phosphorylation of Akt, but not Smad2 1147:1187 Moreover, ST6GAL1 knockdown inhibited the phosphorylation of Akt, but not Smad2, suggesting that ST6GAL1 contributes to EMT through a non-Smad signaling pathway. 25344606 5 26 theme surface 814:820 arg1 E-cadherin 822:831 cell surface E-cadherin 809:831 cell surface E-cadherin 809:831 Conversely, overexpression of ST6GAL1 increased the turnover of cell surface E-cadherin and promoted TGF-β-induced EMT. 25344606 6 27 theme little 922:927 arg1 influence 929:937 little influence 922:937 little influence 922:937 Overexpressing β-galactoside α2,3-sialyltranferase 4 had little influence on EMT, indicating specificity for α2,6-sialylation. 25344606 7 28 theme basal 996:1000 arg1 phenotype 1014:1022 The basal mesenchymal phenotype 992:1022 The basal mesenchymal phenotype of MDA-MB-231 human breast cancer cells 992:1062 The basal mesenchymal phenotype of MDA-MB-231 human breast cancer cells was partially reversed by ST6GAL1 silencing. 25344606 4 29 from increase 651:658 arg1 determinant 694:704 a major determinant 686:704 a major determinant of epithelial cell adherens junctions 686:742 Knockdown of St6gal1 strongly suppressed TGF-β-induced EMT with a concomitant increase in E-cadherin expression, a major determinant of epithelial cell adherens junctions. 25344606 4 29 from increase 651:658 arg1 expression 674:683 E-cadherin expression 663:683 E-cadherin expression 663:683 Knockdown of St6gal1 strongly suppressed TGF-β-induced EMT with a concomitant increase in E-cadherin expression, a major determinant of epithelial cell adherens junctions. 25344606 5 30 theme E-cadherin 822:831 arg1 turnover 797:804 the turnover 793:804 the turnover of cell surface E-cadherin 793:831 Conversely, overexpression of ST6GAL1 increased the turnover of cell surface E-cadherin and promoted TGF-β-induced EMT. 25344606 3 31 theme St6gal1 555:561 arg1 promoter 563:570 the St6gal1 promoter 551:570 the St6gal1 promoter 551:570 Here, we report that St6gal1 transcription and α2,6-sialylated N-glycans are up-regulated during TGF-β-induced epithelial-mesenchymal transition (EMT) in GE11 cells, requiring the Sp1 element within the St6gal1 promoter. 25344606 0 32 theme growth 60:65 arg1 transition 108:117 transforming growth factor-β-mediated epithelial-mesenchymal transition 47:117 transforming growth factor-β-mediated epithelial-mesenchymal transition 47:117 β-Galactoside α2,6-sialyltranferase 1 promotes transforming growth factor-β-mediated epithelial-mesenchymal transition. 25344606 4 33 theme E-cadherin 663:672 arg1 determinant 694:704 a major determinant 686:704 a major determinant of epithelial cell adherens junctions 686:742 Knockdown of St6gal1 strongly suppressed TGF-β-induced EMT with a concomitant increase in E-cadherin expression, a major determinant of epithelial cell adherens junctions. 25344606 4 33 theme E-cadherin 663:672 arg1 expression 674:683 E-cadherin expression 663:683 E-cadherin expression 663:683 Knockdown of St6gal1 strongly suppressed TGF-β-induced EMT with a concomitant increase in E-cadherin expression, a major determinant of epithelial cell adherens junctions. 25344606 9 34 theme malignant 1489:1497 arg1 progression 1499:1509 malignant progression 1489:1509 malignant progression 1489:1509 Taken together, our data indicate that ST6GAL1 promotes TGF-β-dependent EMT as well as maintenance of the mesenchymal state by growth signaling, providing a plausible mechanism whereby up-regulated ST6GAL1 may promote malignant progression. 25344606 9 35 theme growth 1398:1403 arg1 signaling 1405:1413 growth signaling 1398:1413 growth signaling 1398:1413 Taken together, our data indicate that ST6GAL1 promotes TGF-β-dependent EMT as well as maintenance of the mesenchymal state by growth signaling, providing a plausible mechanism whereby up-regulated ST6GAL1 may promote malignant progression. 25344606 0 36 theme transforming 47:58 arg1 transition 108:117 transforming growth factor-β-mediated epithelial-mesenchymal transition 47:117 transforming growth factor-β-mediated epithelial-mesenchymal transition 47:117 β-Galactoside α2,6-sialyltranferase 1 promotes transforming growth factor-β-mediated epithelial-mesenchymal transition. 25344606 8 37 theme signaling 1252:1260 arg1 pathway 1262:1268 a non-Smad signaling pathway 1241:1268 a non-Smad signaling pathway 1241:1268 Moreover, ST6GAL1 knockdown inhibited the phosphorylation of Akt, but not Smad2, suggesting that ST6GAL1 contributes to EMT through a non-Smad signaling pathway. 25344606 2 38 theme Increased 234:242 arg1 expression 244:253 Increased expression 234:253 Increased expression of ST6GAL1 234:264 Increased expression of ST6GAL1 has been reported in diverse carcinomas and highly correlates with tumor progression. 25344606 0 39 theme epithelial-mesenchymal 85:106 arg1 transition 108:117 transforming growth factor-β-mediated epithelial-mesenchymal transition 47:117 transforming growth factor-β-mediated epithelial-mesenchymal transition 47:117 β-Galactoside α2,6-sialyltranferase 1 promotes transforming growth factor-β-mediated epithelial-mesenchymal transition. 25344606 2 40 theme diverse 287:293 arg1 carcinomas 295:304 diverse carcinomas 287:304 diverse carcinomas 287:304 Increased expression of ST6GAL1 has been reported in diverse carcinomas and highly correlates with tumor progression. 25344606 0 41 theme factor-β-mediated 67:83 arg1 transition 108:117 transforming growth factor-β-mediated epithelial-mesenchymal transition 47:117 transforming growth factor-β-mediated epithelial-mesenchymal transition 47:117 β-Galactoside α2,6-sialyltranferase 1 promotes transforming growth factor-β-mediated epithelial-mesenchymal transition. 25344606 4 42 theme concomitant 639:649 arg1 increase 651:658 a concomitant increase 637:658 a concomitant increase in E-cadherin expression, a major determinant of epithelial cell adherens junctions 637:742 Knockdown of St6gal1 strongly suppressed TGF-β-induced EMT with a concomitant increase in E-cadherin expression, a major determinant of epithelial cell adherens junctions. 25344606 3 43 gly α2,6-sialylated 399:413 arg1 N-glycans 415:423 α2,6-sialylated N-glycans 399:423 α2,6-sialylated N-glycans 399:423 Here, we report that St6gal1 transcription and α2,6-sialylated N-glycans are up-regulated during TGF-β-induced epithelial-mesenchymal transition (EMT) in GE11 cells, requiring the Sp1 element within the St6gal1 promoter. 25344606 9 44 theme state 1389:1393 arg1 maintenance 1358:1368 maintenance 1358:1368 TGF-β-dependent EMT as well as maintenance of the mesenchymal state 1327:1393 Taken together, our data indicate that ST6GAL1 promotes TGF-β-dependent EMT as well as maintenance of the mesenchymal state by growth signaling, providing a plausible mechanism whereby up-regulated ST6GAL1 may promote malignant progression. 25344606 9 44 theme state 1389:1393 arg1 EMT 1343:1345 TGF-β-dependent EMT 1327:1345 TGF-β-dependent EMT as well as maintenance of the mesenchymal state 1327:1393 Taken together, our data indicate that ST6GAL1 promotes TGF-β-dependent EMT as well as maintenance of the mesenchymal state by growth signaling, providing a plausible mechanism whereby up-regulated ST6GAL1 may promote malignant progression. 25344606 2 45 theme tumor 333:337 arg1 progression 339:349 tumor progression 333:349 tumor progression 333:349 Increased expression of ST6GAL1 has been reported in diverse carcinomas and highly correlates with tumor progression. 25344606 6 46 theme β-galactoside 880:892 arg1 α2,3-sialyltranferase 894:914 Overexpressing β-galactoside α2,3-sialyltranferase 4 865:916 Overexpressing β-galactoside α2,3-sialyltranferase 4 865:916 Overexpressing β-galactoside α2,3-sialyltranferase 4 had little influence on EMT, indicating specificity for α2,6-sialylation. 25344606 4 47 theme epithelial 709:718 arg1 junctions 734:742 epithelial cell adherens junctions 709:742 epithelial cell adherens junctions 709:742 Knockdown of St6gal1 strongly suppressed TGF-β-induced EMT with a concomitant increase in E-cadherin expression, a major determinant of epithelial cell adherens junctions. 25344606 5 48 theme cell 809:812 arg1 E-cadherin 822:831 cell surface E-cadherin 809:831 cell surface E-cadherin 809:831 Conversely, overexpression of ST6GAL1 increased the turnover of cell surface E-cadherin and promoted TGF-β-induced EMT. 25344606 9 49 theme plausible 1428:1436 arg1 mechanism 1438:1446 a plausible mechanism 1426:1446 a plausible mechanism whereby up-regulated ST6GAL1 may promote malignant progression 1426:1509 Taken together, our data indicate that ST6GAL1 promotes TGF-β-dependent EMT as well as maintenance of the mesenchymal state by growth signaling, providing a plausible mechanism whereby up-regulated ST6GAL1 may promote malignant progression. 25344606 6 50 theme Overexpressing 865:878 arg1 α2,3-sialyltranferase 894:914 Overexpressing β-galactoside α2,3-sialyltranferase 4 865:916 Overexpressing β-galactoside α2,3-sialyltranferase 4 865:916 Overexpressing β-galactoside α2,3-sialyltranferase 4 had little influence on EMT, indicating specificity for α2,6-sialylation. 25344606 3 51 theme α2,6-sialylated 399:413 arg1 N-glycans 415:423 α2,6-sialylated N-glycans 399:423 α2,6-sialylated N-glycans 399:423 Here, we report that St6gal1 transcription and α2,6-sialylated N-glycans are up-regulated during TGF-β-induced epithelial-mesenchymal transition (EMT) in GE11 cells, requiring the Sp1 element within the St6gal1 promoter. 25344606 2 52 theme ST6GAL1 258:264 arg1 expression 244:253 Increased expression 234:253 Increased expression of ST6GAL1 234:264 Increased expression of ST6GAL1 has been reported in diverse carcinomas and highly correlates with tumor progression. 25344606 1 53 theme terminal 194:201 arg1 α2,6-sialylation 203:218 terminal α2,6-sialylation 194:218 terminal α2,6-sialylation 194:218 β-Galactoside α2,6-sialyltranferase 1 (ST6GAL1) catalyzes the addition of terminal α2,6-sialylation to N-glycans. 25344606 4 54 theme adherens 725:732 arg1 junctions 734:742 epithelial cell adherens junctions 709:742 epithelial cell adherens junctions 709:742 Knockdown of St6gal1 strongly suppressed TGF-β-induced EMT with a concomitant increase in E-cadherin expression, a major determinant of epithelial cell adherens junctions. 25344606 6 55 contain had 918:920 arg1 α2,3-sialyltranferase 894:914 Overexpressing β-galactoside α2,3-sialyltranferase 4 865:916 Overexpressing β-galactoside α2,3-sialyltranferase 4 865:916 Overexpressing β-galactoside α2,3-sialyltranferase 4 had little influence on EMT, indicating specificity for α2,6-sialylation. 25344606 6 55 contain had 918:920 arg2 influence 929:937 little influence 922:937 little influence 922:937 Overexpressing β-galactoside α2,3-sialyltranferase 4 had little influence on EMT, indicating specificity for α2,6-sialylation. 25344606 9 56 theme TGF-β-dependent 1327:1341 arg1 EMT 1343:1345 TGF-β-dependent EMT 1327:1345 TGF-β-dependent EMT as well as maintenance of the mesenchymal state 1327:1393 Taken together, our data indicate that ST6GAL1 promotes TGF-β-dependent EMT as well as maintenance of the mesenchymal state by growth signaling, providing a plausible mechanism whereby up-regulated ST6GAL1 may promote malignant progression. 25344606 1 57 theme α2,6-sialylation 203:218 arg1 addition 182:189 the addition 178:189 the addition of terminal α2,6-sialylation to N-glycans 178:231 β-Galactoside α2,6-sialyltranferase 1 (ST6GAL1) catalyzes the addition of terminal α2,6-sialylation to N-glycans. 25344606 7 58 theme cancer 1051:1056 arg1 cells 1058:1062 MDA-MB-231 human breast cancer cells 1027:1062 MDA-MB-231 human breast cancer cells 1027:1062 The basal mesenchymal phenotype of MDA-MB-231 human breast cancer cells was partially reversed by ST6GAL1 silencing. 25344606 4 59 theme cell 720:723 arg1 junctions 734:742 epithelial cell adherens junctions 709:742 epithelial cell adherens junctions 709:742 Knockdown of St6gal1 strongly suppressed TGF-β-induced EMT with a concomitant increase in E-cadherin expression, a major determinant of epithelial cell adherens junctions. 27452734 5 0 theme phase 808:812 arg1 extraction 814:823 solid phase extraction 802:823 solid phase extraction of glycosite-containing peptides (SPEG) 802:863 Using solid phase extraction of glycosite-containing peptides (SPEG), we were able to identify 799 unique N-linked glycosylation sites (glycosites) in platelets, representing the largest and the most comprehensive analysis to date. 27452734 4 1 theme stimulated 738:747 arg1 states 749:754 resting and stimulated states 726:754 resting and stimulated states 726:754 The platelet glycoproteome, was studied using an iTRAQ in resting and stimulated states and with and without aspirin treatment. 27452734 3 2 from impact 489:494 arg1 glycoproteome 606:618 the platelet glycoproteome 593:618 the platelet glycoproteome 593:618 To study the impact of aspirin, which is commonly prescribed for primary and secondary cardiovascular prevention, on the platelet glycoproteome, we evaluated washed platelets from ten donors. 27452734 3 3 theme primary 541:547 arg1 prevention 578:587 primary and secondary cardiovascular prevention 541:587 primary and secondary cardiovascular prevention 541:587 To study the impact of aspirin, which is commonly prescribed for primary and secondary cardiovascular prevention, on the platelet glycoproteome, we evaluated washed platelets from ten donors. 27452734 1 4 gly glycoproteins 92:104 arg1 glycoproteins 92:104 Platelet glycoproteins 83:104 Platelet glycoproteins 83:104 Platelet glycoproteins are known to play central roles in hemostasis and vascular integrity and have pathologic roles in vascular occlusive diseases such as myocardial infarction and stroke. 27452734 2 5 theme vascular 390:397 arg1 pathologies 399:409 vascular pathologies 390:409 vascular pathologies 390:409 Characterizing glycoproteins within and secreted by platelets can provide insight into the mechanisms that underlie vascular pathologies and the therapeutic benefits or failure of anti-platelet agents. 27452734 7 6 theme metallopeptidase 1221:1236 arg1 TIMP1 1251:1255 TIMP1 1251:1255 TIMP1 1251:1255 In our analyses, metallopeptidase inhibitor 1 (TIMP1) was the single most significantly affected glycoprotein by aspirin treatment. 27452734 7 6 theme metallopeptidase 1221:1236 arg1 inhibitor 1238:1246 metallopeptidase inhibitor 1 1221:1248 metallopeptidase inhibitor 1 (TIMP1) 1221:1256 In our analyses, metallopeptidase inhibitor 1 (TIMP1) was the single most significantly affected glycoprotein by aspirin treatment. 27452734 7 6 theme metallopeptidase 1221:1236 arg1 glycoprotein 1301:1312 the single most significantly affected glycoprotein 1262:1312 the single most significantly affected glycoprotein by aspirin treatment 1262:1333 In our analyses, metallopeptidase inhibitor 1 (TIMP1) was the single most significantly affected glycoprotein by aspirin treatment. 27452734 5 7 gly glycosylation 911:923 arg2 sites 925:929 799 unique N-linked glycosylation sites 891:929 799 unique N-linked glycosylation sites (glycosites) in platelets 891:955 Using solid phase extraction of glycosite-containing peptides (SPEG), we were able to identify 799 unique N-linked glycosylation sites (glycosites) in platelets, representing the largest and the most comprehensive analysis to date. 27452734 5 7 gly glycosylation 911:923 arg2 799 891:893 799 891:893 799 891:893 Using solid phase extraction of glycosite-containing peptides (SPEG), we were able to identify 799 unique N-linked glycosylation sites (glycosites) in platelets, representing the largest and the most comprehensive analysis to date. 27452734 5 7 gly glycosylation 911:923 arg2 glycosites 932:941 glycosites 932:941 glycosites 932:941 Using solid phase extraction of glycosite-containing peptides (SPEG), we were able to identify 799 unique N-linked glycosylation sites (glycosites) in platelets, representing the largest and the most comprehensive analysis to date. 27452734 3 8 theme secondary 553:561 arg1 prevention 578:587 primary and secondary cardiovascular prevention 541:587 primary and secondary cardiovascular prevention 541:587 To study the impact of aspirin, which is commonly prescribed for primary and secondary cardiovascular prevention, on the platelet glycoproteome, we evaluated washed platelets from ten donors. 27452734 6 9 theme platelets 1165:1173 arg1 analysis 1153:1160 global proteomics analysis 1135:1160 global proteomics analysis of platelets and their secreted proteins 1135:1201 We were able to identity a number of glycoproteins impacted by aspirin treatment, which we validated using global proteomics analysis of platelets and their secreted proteins. 27452734 11 10 theme platelet 1798:1805 arg1 response 1807:1814 platelet response 1798:1814 platelet response to aspirin or other anti-platelet therapies 1798:1858 If validated, our findings may be useful for developing assays that assess platelet response to aspirin or other anti-platelet therapies. 27452734 6 11 theme secreted 1185:1192 arg1 proteins 1194:1201 their secreted proteins 1179:1201 their secreted proteins 1179:1201 We were able to identity a number of glycoproteins impacted by aspirin treatment, which we validated using global proteomics analysis of platelets and their secreted proteins. 27452734 1 12 contain have 179:182 arg1 glycoproteins 92:104 Platelet glycoproteins 83:104 Platelet glycoproteins 83:104 Platelet glycoproteins are known to play central roles in hemostasis and vascular integrity and have pathologic roles in vascular occlusive diseases such as myocardial infarction and stroke. 27452734 1 12 contain have 179:182 arg2 roles 195:199 pathologic roles 184:199 pathologic roles 184:199 Platelet glycoproteins are known to play central roles in hemostasis and vascular integrity and have pathologic roles in vascular occlusive diseases such as myocardial infarction and stroke. 27452734 5 13 theme comprehensive 996:1008 arg1 analysis 1010:1017 the most comprehensive analysis 987:1017 the most comprehensive analysis to date 987:1025 Using solid phase extraction of glycosite-containing peptides (SPEG), we were able to identify 799 unique N-linked glycosylation sites (glycosites) in platelets, representing the largest and the most comprehensive analysis to date. 27452734 5 14 from sites 925:929 arg1 platelets 947:955 platelets 947:955 platelets 947:955 Using solid phase extraction of glycosite-containing peptides (SPEG), we were able to identify 799 unique N-linked glycosylation sites (glycosites) in platelets, representing the largest and the most comprehensive analysis to date. 27452734 1 15 theme Platelet 83:90 arg1 glycoproteins 92:104 Platelet glycoproteins 83:104 Platelet glycoproteins 83:104 Platelet glycoproteins are known to play central roles in hemostasis and vascular integrity and have pathologic roles in vascular occlusive diseases such as myocardial infarction and stroke. 27452734 4 16 from iTRAQ 717:721 arg1 states 749:754 resting and stimulated states 726:754 resting and stimulated states 726:754 The platelet glycoproteome, was studied using an iTRAQ in resting and stimulated states and with and without aspirin treatment. 27452734 7 17 theme affected 1292:1299 arg1 inhibitor 1238:1246 metallopeptidase inhibitor 1 1221:1248 metallopeptidase inhibitor 1 (TIMP1) 1221:1256 In our analyses, metallopeptidase inhibitor 1 (TIMP1) was the single most significantly affected glycoprotein by aspirin treatment. 27452734 7 17 theme affected 1292:1299 arg1 glycoprotein 1301:1312 the single most significantly affected glycoprotein 1262:1312 the single most significantly affected glycoprotein by aspirin treatment 1262:1333 In our analyses, metallopeptidase inhibitor 1 (TIMP1) was the single most significantly affected glycoprotein by aspirin treatment. 27452734 7 18 theme single 1266:1271 arg1 inhibitor 1238:1246 metallopeptidase inhibitor 1 1221:1248 metallopeptidase inhibitor 1 (TIMP1) 1221:1256 In our analyses, metallopeptidase inhibitor 1 (TIMP1) was the single most significantly affected glycoprotein by aspirin treatment. 27452734 7 18 theme single 1266:1271 arg1 glycoprotein 1301:1312 the single most significantly affected glycoprotein 1262:1312 the single most significantly affected glycoprotein by aspirin treatment 1262:1333 In our analyses, metallopeptidase inhibitor 1 (TIMP1) was the single most significantly affected glycoprotein by aspirin treatment. 27452734 5 19 link N-linked 902:909 arg1 glycosites 932:941 glycosites 932:941 glycosites 932:941 Using solid phase extraction of glycosite-containing peptides (SPEG), we were able to identify 799 unique N-linked glycosylation sites (glycosites) in platelets, representing the largest and the most comprehensive analysis to date. 27452734 5 19 link N-linked 902:909 arg1 sites 925:929 799 unique N-linked glycosylation sites 891:929 799 unique N-linked glycosylation sites (glycosites) in platelets 891:955 Using solid phase extraction of glycosite-containing peptides (SPEG), we were able to identify 799 unique N-linked glycosylation sites (glycosites) in platelets, representing the largest and the most comprehensive analysis to date. 27452734 4 20 theme platelet 672:679 arg1 glycoproteome 681:693 The platelet glycoproteome 668:693 The platelet glycoproteome 668:693 The platelet glycoproteome, was studied using an iTRAQ in resting and stimulated states and with and without aspirin treatment. 27452734 3 21 from donors 660:665 arg1 platelets 641:649 washed platelets 634:649 washed platelets from ten donors 634:665 To study the impact of aspirin, which is commonly prescribed for primary and secondary cardiovascular prevention, on the platelet glycoproteome, we evaluated washed platelets from ten donors. 27452734 1 22 theme pathologic 184:193 arg1 roles 195:199 pathologic roles 184:199 pathologic roles 184:199 Platelet glycoproteins are known to play central roles in hemostasis and vascular integrity and have pathologic roles in vascular occlusive diseases such as myocardial infarction and stroke. 27452734 9 23 theme platelet 1484:1491 arg1 reactivity 1493:1502 platelet reactivity 1484:1502 platelet reactivity 1484:1502 Functional analysis demonstrated that TIMP1 levels were highly correlated with platelet reactivity in vitro, with a correlation coefficient of -0.5. 27452734 6 24 theme proteins 1194:1201 arg1 analysis 1153:1160 global proteomics analysis 1135:1160 global proteomics analysis of platelets and their secreted proteins 1135:1201 We were able to identity a number of glycoproteins impacted by aspirin treatment, which we validated using global proteomics analysis of platelets and their secreted proteins. 27452734 5 25 theme unique 895:900 arg1 glycosites 932:941 glycosites 932:941 glycosites 932:941 Using solid phase extraction of glycosite-containing peptides (SPEG), we were able to identify 799 unique N-linked glycosylation sites (glycosites) in platelets, representing the largest and the most comprehensive analysis to date. 27452734 5 25 theme unique 895:900 arg1 sites 925:929 799 unique N-linked glycosylation sites 891:929 799 unique N-linked glycosylation sites (glycosites) in platelets 891:955 Using solid phase extraction of glycosite-containing peptides (SPEG), we were able to identify 799 unique N-linked glycosylation sites (glycosites) in platelets, representing the largest and the most comprehensive analysis to date. 27452734 2 26 gly glycoproteins 289:301 arg1 glycoproteins 289:301 Characterizing glycoproteins 274:301 Characterizing glycoproteins within and secreted by platelets 274:334 Characterizing glycoproteins within and secreted by platelets can provide insight into the mechanisms that underlie vascular pathologies and the therapeutic benefits or failure of anti-platelet agents. 27452734 11 27 theme other 1830:1834 arg1 therapies 1850:1858 other anti-platelet therapies 1830:1858 other anti-platelet therapies 1830:1858 If validated, our findings may be useful for developing assays that assess platelet response to aspirin or other anti-platelet therapies. 27452734 10 28 theme aspirin 1638:1644 arg1 treatment 1646:1654 aspirin treatment 1638:1654 aspirin treatment 1638:1654 The release of TIMP1 from platelets, which was previously unknown to be affected by aspirin treatment, may play important roles in hemostasis and/or vascular integrity. 27452734 4 29 theme aspirin 777:783 arg1 treatment 785:793 aspirin treatment 777:793 aspirin treatment 777:793 The platelet glycoproteome, was studied using an iTRAQ in resting and stimulated states and with and without aspirin treatment. 27452734 6 30 theme aspirin 1091:1097 arg1 treatment 1099:1107 aspirin treatment 1091:1107 aspirin treatment 1091:1107 We were able to identity a number of glycoproteins impacted by aspirin treatment, which we validated using global proteomics analysis of platelets and their secreted proteins. 27452734 5 31 theme N-linked 902:909 arg1 glycosites 932:941 glycosites 932:941 glycosites 932:941 Using solid phase extraction of glycosite-containing peptides (SPEG), we were able to identify 799 unique N-linked glycosylation sites (glycosites) in platelets, representing the largest and the most comprehensive analysis to date. 27452734 5 31 theme N-linked 902:909 arg1 sites 925:929 799 unique N-linked glycosylation sites 891:929 799 unique N-linked glycosylation sites (glycosites) in platelets 891:955 Using solid phase extraction of glycosite-containing peptides (SPEG), we were able to identify 799 unique N-linked glycosylation sites (glycosites) in platelets, representing the largest and the most comprehensive analysis to date. 27452734 0 32 theme Platelet 0:7 arg1 glycoproteins 9:21 Platelet glycoproteins 0:21 Platelet glycoproteins 0:21 Platelet glycoproteins associated with aspirin-treatment upon platelet activation. 27452734 11 33 theme anti-platelet 1836:1848 arg1 therapies 1850:1858 other anti-platelet therapies 1830:1858 other anti-platelet therapies 1830:1858 If validated, our findings may be useful for developing assays that assess platelet response to aspirin or other anti-platelet therapies. 27452734 7 34 from glycoprotein 1301:1312 arg1 analyses 1211:1218 our analyses 1207:1218 our analyses 1207:1218 In our analyses, metallopeptidase inhibitor 1 (TIMP1) was the single most significantly affected glycoprotein by aspirin treatment. 27452734 2 35 theme therapeutic 419:429 arg1 benefits 431:438 the therapeutic benefits 415:438 the therapeutic benefits 415:438 Characterizing glycoproteins within and secreted by platelets can provide insight into the mechanisms that underlie vascular pathologies and the therapeutic benefits or failure of anti-platelet agents. 27452734 6 36 gly glycoproteins 1065:1077 arg1 glycoproteins 1065:1077 glycoproteins 1065:1077 glycoproteins impacted by aspirin treatment 1065:1107 We were able to identity a number of glycoproteins impacted by aspirin treatment, which we validated using global proteomics analysis of platelets and their secreted proteins. 27452734 3 37 theme platelet 597:604 arg1 glycoproteome 606:618 the platelet glycoproteome 593:618 the platelet glycoproteome 593:618 To study the impact of aspirin, which is commonly prescribed for primary and secondary cardiovascular prevention, on the platelet glycoproteome, we evaluated washed platelets from ten donors. 27452734 1 38 theme occlusive 213:221 arg1 diseases 223:230 vascular occlusive diseases 204:230 vascular occlusive diseases such as myocardial infarction and stroke 204:271 Platelet glycoproteins are known to play central roles in hemostasis and vascular integrity and have pathologic roles in vascular occlusive diseases such as myocardial infarction and stroke. 27452734 1 38 theme occlusive 213:221 arg1 stroke 266:271 stroke 266:271 stroke 266:271 Platelet glycoproteins are known to play central roles in hemostasis and vascular integrity and have pathologic roles in vascular occlusive diseases such as myocardial infarction and stroke. 27452734 1 38 theme occlusive 213:221 arg1 infarction 251:260 myocardial infarction 240:260 myocardial infarction 240:260 Platelet glycoproteins are known to play central roles in hemostasis and vascular integrity and have pathologic roles in vascular occlusive diseases such as myocardial infarction and stroke. 27452734 1 39 theme central 124:130 arg1 roles 132:136 central roles 124:136 central roles 124:136 Platelet glycoproteins are known to play central roles in hemostasis and vascular integrity and have pathologic roles in vascular occlusive diseases such as myocardial infarction and stroke. 27452734 2 40 theme agents 468:473 arg1 pathologies 399:409 vascular pathologies 390:409 vascular pathologies 390:409 Characterizing glycoproteins within and secreted by platelets can provide insight into the mechanisms that underlie vascular pathologies and the therapeutic benefits or failure of anti-platelet agents. 27452734 2 40 theme agents 468:473 arg1 failure 443:449 failure 443:449 failure of anti-platelet agents 443:473 Characterizing glycoproteins within and secreted by platelets can provide insight into the mechanisms that underlie vascular pathologies and the therapeutic benefits or failure of anti-platelet agents. 27452734 2 40 theme agents 468:473 arg1 benefits 431:438 the therapeutic benefits 415:438 the therapeutic benefits 415:438 Characterizing glycoproteins within and secreted by platelets can provide insight into the mechanisms that underlie vascular pathologies and the therapeutic benefits or failure of anti-platelet agents. 27452734 10 41 theme important 1666:1674 arg1 roles 1676:1680 important roles 1666:1680 important roles 1666:1680 The release of TIMP1 from platelets, which was previously unknown to be affected by aspirin treatment, may play important roles in hemostasis and/or vascular integrity. 27452734 8 42 theme proteomic 1359:1367 arg1 results 1369:1375 proteomic results 1359:1375 proteomic results 1359:1375 ELISA assays confirmed proteomic results and validated our strategy. 27452734 7 43 theme aspirin 1317:1323 arg1 treatment 1325:1333 aspirin treatment 1317:1333 aspirin treatment 1317:1333 In our analyses, metallopeptidase inhibitor 1 (TIMP1) was the single most significantly affected glycoprotein by aspirin treatment. 27452734 1 44 theme vascular 204:211 arg1 diseases 223:230 vascular occlusive diseases 204:230 vascular occlusive diseases such as myocardial infarction and stroke 204:271 Platelet glycoproteins are known to play central roles in hemostasis and vascular integrity and have pathologic roles in vascular occlusive diseases such as myocardial infarction and stroke. 27452734 1 44 theme vascular 204:211 arg1 stroke 266:271 stroke 266:271 stroke 266:271 Platelet glycoproteins are known to play central roles in hemostasis and vascular integrity and have pathologic roles in vascular occlusive diseases such as myocardial infarction and stroke. 27452734 1 44 theme vascular 204:211 arg1 infarction 251:260 myocardial infarction 240:260 myocardial infarction 240:260 Platelet glycoproteins are known to play central roles in hemostasis and vascular integrity and have pathologic roles in vascular occlusive diseases such as myocardial infarction and stroke. 27452734 2 45 theme anti-platelet 454:466 arg1 agents 468:473 anti-platelet agents 454:473 anti-platelet agents 454:473 Characterizing glycoproteins within and secreted by platelets can provide insight into the mechanisms that underlie vascular pathologies and the therapeutic benefits or failure of anti-platelet agents. 27452734 4 46 theme resting 726:732 arg1 states 749:754 resting and stimulated states 726:754 resting and stimulated states 726:754 The platelet glycoproteome, was studied using an iTRAQ in resting and stimulated states and with and without aspirin treatment. 27452734 5 47 theme glycosite-containing 828:847 arg1 peptides 849:856 glycosite-containing peptides 828:856 glycosite-containing peptides (SPEG) 828:863 Using solid phase extraction of glycosite-containing peptides (SPEG), we were able to identify 799 unique N-linked glycosylation sites (glycosites) in platelets, representing the largest and the most comprehensive analysis to date. 27452734 5 47 theme glycosite-containing 828:847 arg1 SPEG 859:862 SPEG 859:862 SPEG 859:862 Using solid phase extraction of glycosite-containing peptides (SPEG), we were able to identify 799 unique N-linked glycosylation sites (glycosites) in platelets, representing the largest and the most comprehensive analysis to date. 27452734 0 48 gly glycoproteins 9:21 arg1 glycoproteins 9:21 Platelet glycoproteins 0:21 Platelet glycoproteins 0:21 Platelet glycoproteins associated with aspirin-treatment upon platelet activation. 27452734 6 49 theme glycoproteins 1065:1077 arg1 number 1055:1060 a number 1053:1060 a number 1053:1060 We were able to identity a number of glycoproteins impacted by aspirin treatment, which we validated using global proteomics analysis of platelets and their secreted proteins. 27452734 3 50 theme aspirin 499:505 arg1 impact 489:494 the impact 485:494 the impact of aspirin, which is commonly prescribed for primary and secondary cardiovascular prevention, on the platelet glycoproteome 485:618 To study the impact of aspirin, which is commonly prescribed for primary and secondary cardiovascular prevention, on the platelet glycoproteome, we evaluated washed platelets from ten donors. 27452734 5 51 theme peptides 849:856 arg1 extraction 814:823 solid phase extraction 802:823 solid phase extraction of glycosite-containing peptides (SPEG) 802:863 Using solid phase extraction of glycosite-containing peptides (SPEG), we were able to identify 799 unique N-linked glycosylation sites (glycosites) in platelets, representing the largest and the most comprehensive analysis to date. 27452734 9 52 theme Functional 1405:1414 arg1 analysis 1416:1423 Functional analysis 1405:1423 Functional analysis 1405:1423 Functional analysis demonstrated that TIMP1 levels were highly correlated with platelet reactivity in vitro, with a correlation coefficient of -0.5. 27452734 10 53 from platelets 1580:1588 arg1 release 1558:1564 The release 1554:1564 The release of TIMP1 from platelets, which was previously unknown to be affected by aspirin treatment, 1554:1655 The release of TIMP1 from platelets, which was previously unknown to be affected by aspirin treatment, may play important roles in hemostasis and/or vascular integrity. 27452734 9 54 theme correlation 1521:1531 arg1 coefficient 1533:1543 a correlation coefficient 1519:1543 a correlation coefficient of -0.5 1519:1551 Functional analysis demonstrated that TIMP1 levels were highly correlated with platelet reactivity in vitro, with a correlation coefficient of -0.5. 27452734 10 55 theme TIMP1 1569:1573 arg1 release 1558:1564 The release 1554:1564 The release of TIMP1 from platelets, which was previously unknown to be affected by aspirin treatment, 1554:1655 The release of TIMP1 from platelets, which was previously unknown to be affected by aspirin treatment, may play important roles in hemostasis and/or vascular integrity. 27452734 0 56 theme platelet 62:69 arg1 activation 71:80 platelet activation 62:80 platelet activation 62:80 Platelet glycoproteins associated with aspirin-treatment upon platelet activation. 27452734 7 57 gly glycoprotein 1301:1312 arg1 inhibitor 1238:1246 metallopeptidase inhibitor 1 1221:1248 metallopeptidase inhibitor 1 (TIMP1) 1221:1256 In our analyses, metallopeptidase inhibitor 1 (TIMP1) was the single most significantly affected glycoprotein by aspirin treatment. 27452734 7 57 gly glycoprotein 1301:1312 arg1 glycoprotein 1301:1312 the single most significantly affected glycoprotein 1262:1312 the single most significantly affected glycoprotein by aspirin treatment 1262:1333 In our analyses, metallopeptidase inhibitor 1 (TIMP1) was the single most significantly affected glycoprotein by aspirin treatment. 27452734 3 58 theme washed 634:639 arg1 platelets 641:649 washed platelets 634:649 washed platelets from ten donors 634:665 To study the impact of aspirin, which is commonly prescribed for primary and secondary cardiovascular prevention, on the platelet glycoproteome, we evaluated washed platelets from ten donors. 27452734 9 59 theme -0.5 1548:1551 arg1 coefficient 1533:1543 a correlation coefficient 1519:1543 a correlation coefficient of -0.5 1519:1551 Functional analysis demonstrated that TIMP1 levels were highly correlated with platelet reactivity in vitro, with a correlation coefficient of -0.5. 27452734 6 60 theme proteomics 1142:1151 arg1 analysis 1153:1160 global proteomics analysis 1135:1160 global proteomics analysis of platelets and their secreted proteins 1135:1201 We were able to identity a number of glycoproteins impacted by aspirin treatment, which we validated using global proteomics analysis of platelets and their secreted proteins. 27452734 5 61 theme glycosylation 911:923 arg1 glycosites 932:941 glycosites 932:941 glycosites 932:941 Using solid phase extraction of glycosite-containing peptides (SPEG), we were able to identify 799 unique N-linked glycosylation sites (glycosites) in platelets, representing the largest and the most comprehensive analysis to date. 27452734 5 61 theme glycosylation 911:923 arg1 sites 925:929 799 unique N-linked glycosylation sites 891:929 799 unique N-linked glycosylation sites (glycosites) in platelets 891:955 Using solid phase extraction of glycosite-containing peptides (SPEG), we were able to identify 799 unique N-linked glycosylation sites (glycosites) in platelets, representing the largest and the most comprehensive analysis to date. 27452734 1 62 theme myocardial 240:249 arg1 infarction 251:260 myocardial infarction 240:260 myocardial infarction 240:260 Platelet glycoproteins are known to play central roles in hemostasis and vascular integrity and have pathologic roles in vascular occlusive diseases such as myocardial infarction and stroke. 27452734 5 63 gly glycosites 932:941 arg2 sites 925:929 799 unique N-linked glycosylation sites 891:929 799 unique N-linked glycosylation sites (glycosites) in platelets 891:955 Using solid phase extraction of glycosite-containing peptides (SPEG), we were able to identify 799 unique N-linked glycosylation sites (glycosites) in platelets, representing the largest and the most comprehensive analysis to date. 27452734 5 63 gly glycosites 932:941 arg2 glycosites 932:941 glycosites 932:941 glycosites 932:941 Using solid phase extraction of glycosite-containing peptides (SPEG), we were able to identify 799 unique N-linked glycosylation sites (glycosites) in platelets, representing the largest and the most comprehensive analysis to date. 27452734 9 64 theme TIMP1 1443:1447 arg1 levels 1449:1454 TIMP1 levels 1443:1454 TIMP1 levels 1443:1454 Functional analysis demonstrated that TIMP1 levels were highly correlated with platelet reactivity in vitro, with a correlation coefficient of -0.5. 27452734 6 65 theme global 1135:1140 arg1 analysis 1153:1160 global proteomics analysis 1135:1160 global proteomics analysis of platelets and their secreted proteins 1135:1201 We were able to identity a number of glycoproteins impacted by aspirin treatment, which we validated using global proteomics analysis of platelets and their secreted proteins. 27452734 8 66 theme ELISA 1336:1340 arg1 assays 1342:1347 ELISA assays 1336:1347 ELISA assays 1336:1347 ELISA assays confirmed proteomic results and validated our strategy. 27452734 10 67 theme vascular 1703:1710 arg1 integrity 1712:1720 vascular integrity 1703:1720 vascular integrity 1703:1720 The release of TIMP1 from platelets, which was previously unknown to be affected by aspirin treatment, may play important roles in hemostasis and/or vascular integrity. 27452734 2 68 theme Characterizing 274:287 arg1 glycoproteins 289:301 Characterizing glycoproteins 274:301 Characterizing glycoproteins within and secreted by platelets 274:334 Characterizing glycoproteins within and secreted by platelets can provide insight into the mechanisms that underlie vascular pathologies and the therapeutic benefits or failure of anti-platelet agents. 27452734 1 69 theme vascular 156:163 arg1 integrity 165:173 vascular integrity 156:173 vascular integrity 156:173 Platelet glycoproteins are known to play central roles in hemostasis and vascular integrity and have pathologic roles in vascular occlusive diseases such as myocardial infarction and stroke. 27452734 5 70 theme solid 802:806 arg1 extraction 814:823 solid phase extraction 802:823 solid phase extraction of glycosite-containing peptides (SPEG) 802:863 Using solid phase extraction of glycosite-containing peptides (SPEG), we were able to identify 799 unique N-linked glycosylation sites (glycosites) in platelets, representing the largest and the most comprehensive analysis to date. 27452734 3 71 theme cardiovascular 563:576 arg1 prevention 578:587 primary and secondary cardiovascular prevention 541:587 primary and secondary cardiovascular prevention 541:587 To study the impact of aspirin, which is commonly prescribed for primary and secondary cardiovascular prevention, on the platelet glycoproteome, we evaluated washed platelets from ten donors. 25499264 12 0 contain had 1952:1954 arg2 effects 1966:1972 no marked effects 1956:1972 no marked effects on CBA susceptibility 1956:1994 Single gp41 glycan deletions had no marked effects on CBA susceptibility, whereas some combinations of two to three gp41 glycan-deletions had a minor effect on CBA activity. 25499264 12 0 contain had 1952:1954 arg1 deletions 1942:1950 Single gp41 glycan deletions 1923:1950 Single gp41 glycan deletions 1923:1950 Single gp41 glycan deletions had no marked effects on CBA susceptibility, whereas some combinations of two to three gp41 glycan-deletions had a minor effect on CBA activity. 25499264 13 1 theme several 2278:2284 arg1 strains 2292:2298 several virus strains 2278:2298 several virus strains 2278:2298 CONCLUSIONS: We revealed the importance of some gp41 N-linked glycans, in particular the N616 glycan which was shown to be absolutely indispensable for the infectivity potential of several virus strains. 25499264 6 2 gly glycosylation 1128:1140 arg2 site 1142:1145 an intact N616 glycosylation site 1113:1145 an intact N616 glycosylation site 1113:1145 In particular, lack of an intact N616 glycosylation site was shown to result in the loss of viral infectivity of several (i.e. the X4-tropic IIIB and NL4.3 strains, and the X4/R5-tropic HE strain), but not all (i.e. the R5-tropic ADA strain) studied HIV-1 strains. 25499264 6 3 theme studied 1332:1338 arg1 strains 1346:1352 several (i.e. the X4-tropic IIIB and NL4.3 strains, and the X4/R5-tropic HE strain), but not all (i.e. the R5-tropic ADA strain) studied HIV-1 strains 1203:1352 several (i.e. the X4-tropic IIIB and NL4.3 strains, and the X4/R5-tropic HE strain), but not all (i.e. the R5-tropic ADA strain) studied HIV-1 strains 1203:1352 In particular, lack of an intact N616 glycosylation site was shown to result in the loss of viral infectivity of several (i.e. the X4-tropic IIIB and NL4.3 strains, and the X4/R5-tropic HE strain), but not all (i.e. the R5-tropic ADA strain) studied HIV-1 strains. 25499264 1 4 theme HIV-1 251:255 arg1 glycoproteins 266:278 the HIV-1 envelope glycoproteins 247:278 the HIV-1 envelope glycoproteins 247:278 BACKGROUND: Carbohydrate-binding agents (CBAs) are potent antiretroviral compounds that target the N-glycans on the HIV-1 envelope glycoproteins. 25499264 6 5 theme intact 1116:1121 arg1 site 1142:1145 an intact N616 glycosylation site 1113:1145 an intact N616 glycosylation site 1113:1145 In particular, lack of an intact N616 glycosylation site was shown to result in the loss of viral infectivity of several (i.e. the X4-tropic IIIB and NL4.3 strains, and the X4/R5-tropic HE strain), but not all (i.e. the R5-tropic ADA strain) studied HIV-1 strains. 25499264 6 6 theme infectivity 1188:1198 arg1 loss 1174:1177 the loss 1170:1177 the loss of viral infectivity of several (i.e. the X4-tropic IIIB and NL4.3 strains, and the X4/R5-tropic HE strain), but not all (i.e. the R5-tropic ADA strain) studied HIV-1 strains 1170:1352 In particular, lack of an intact N616 glycosylation site was shown to result in the loss of viral infectivity of several (i.e. the X4-tropic IIIB and NL4.3 strains, and the X4/R5-tropic HE strain), but not all (i.e. the R5-tropic ADA strain) studied HIV-1 strains. 25499264 8 7 theme similar 1553:1559 arg1 levels 1546:1551 gp120 levels 1540:1551 gp120 levels similar to the gp120 levels in WT HIV-1ADA virus 1540:1600 In contrast, N616Q gp41 mutant HIV-1ADA contained gp120 levels similar to the gp120 levels in WT HIV-1ADA virus. 25499264 8 8 theme mutant 1514:1519 arg1 HIV-1ADA 1521:1528 N616Q gp41 mutant HIV-1ADA 1503:1528 N616Q gp41 mutant HIV-1ADA 1503:1528 In contrast, N616Q gp41 mutant HIV-1ADA contained gp120 levels similar to the gp120 levels in WT HIV-1ADA virus. 25499264 10 9 contain have 1765:1768 arg1 CBAs 1760:1763 CBAs 1760:1763 CBAs 1760:1763 Using surface plasmon resonance technology we showed that CBAs have a pronounced affinity for both gp120 and gp41. 25499264 10 9 contain have 1765:1768 arg2 affinity 1783:1790 a pronounced affinity 1770:1790 a pronounced affinity for both gp120 and gp41 1770:1814 Using surface plasmon resonance technology we showed that CBAs have a pronounced affinity for both gp120 and gp41. 25499264 11 10 theme CBAs 1852:1855 arg1 dependent 1864:1872 dependent 1864:1872 dependent 1864:1872 However, the antiviral activity of CBAs is not dependent on the concomitant presence of all gp41 glycans. 25499264 11 10 theme CBAs 1852:1855 arg1 activity 1840:1847 the antiviral activity 1826:1847 the antiviral activity of CBAs 1826:1855 However, the antiviral activity of CBAs is not dependent on the concomitant presence of all gp41 glycans. 25499264 13 11 theme glycans 2159:2165 arg1 importance 2126:2135 the importance 2122:2135 the importance of some gp41 N-linked glycans 2122:2165 CONCLUSIONS: We revealed the importance of some gp41 N-linked glycans, in particular the N616 glycan which was shown to be absolutely indispensable for the infectivity potential of several virus strains. 25499264 4 12 theme DC-SIGN 849:855 arg1 cells 860:864 DC-SIGN(+) cells 849:864 DC-SIGN(+) cells 849:864 RESULTS: We generated HIV-1 mutants lacking gp41 N-glycans and determined the influence of these glycan deletions on the viral phenotype (infectivity, CD4 binding, envelope glycoprotein incorporation in the viral particle and on the transfected cell, virus capture by DC-SIGN(+) cells and transmission of DC-SIGN-captured virions to CD4(+) T-lymphocytes) and on the phenotypic susceptibility of HIV-1 to a selection of CBAs. 25499264 13 13 theme virus 2286:2290 arg1 strains 2292:2298 several virus strains 2278:2298 several virus strains 2278:2298 CONCLUSIONS: We revealed the importance of some gp41 N-linked glycans, in particular the N616 glycan which was shown to be absolutely indispensable for the infectivity potential of several virus strains. 25499264 4 14 theme glycan 678:683 arg1 deletions 685:693 these glycan deletions 672:693 these glycan deletions 672:693 RESULTS: We generated HIV-1 mutants lacking gp41 N-glycans and determined the influence of these glycan deletions on the viral phenotype (infectivity, CD4 binding, envelope glycoprotein incorporation in the viral particle and on the transfected cell, virus capture by DC-SIGN(+) cells and transmission of DC-SIGN-captured virions to CD4(+) T-lymphocytes) and on the phenotypic susceptibility of HIV-1 to a selection of CBAs. 25499264 11 15 theme concomitant 1881:1891 arg1 presence 1893:1900 the concomitant presence 1877:1900 the concomitant presence of all gp41 glycans 1877:1920 However, the antiviral activity of CBAs is not dependent on the concomitant presence of all gp41 glycans. 25499264 6 16 dep IIIB 1231:1234 arg1 i.e. 1212:1215 i.e. 1212:1215 i.e. 1212:1215 In particular, lack of an intact N616 glycosylation site was shown to result in the loss of viral infectivity of several (i.e. the X4-tropic IIIB and NL4.3 strains, and the X4/R5-tropic HE strain), but not all (i.e. the R5-tropic ADA strain) studied HIV-1 strains. 25499264 8 17 contain contained 1530:1538 arg1 HIV-1ADA 1521:1528 N616Q gp41 mutant HIV-1ADA 1503:1528 N616Q gp41 mutant HIV-1ADA 1503:1528 In contrast, N616Q gp41 mutant HIV-1ADA contained gp120 levels similar to the gp120 levels in WT HIV-1ADA virus. 25499264 8 17 contain contained 1530:1538 arg1 contrast 1493:1500 contrast 1493:1500 contrast 1493:1500 In contrast, N616Q gp41 mutant HIV-1ADA contained gp120 levels similar to the gp120 levels in WT HIV-1ADA virus. 25499264 8 17 contain contained 1530:1538 arg2 HIV-1ADA 1521:1528 N616Q gp41 mutant HIV-1ADA 1503:1528 N616Q gp41 mutant HIV-1ADA 1503:1528 In contrast, N616Q gp41 mutant HIV-1ADA contained gp120 levels similar to the gp120 levels in WT HIV-1ADA virus. 25499264 8 17 contain contained 1530:1538 arg2 levels 1546:1551 gp120 levels 1540:1551 gp120 levels similar to the gp120 levels in WT HIV-1ADA virus 1540:1600 In contrast, N616Q gp41 mutant HIV-1ADA contained gp120 levels similar to the gp120 levels in WT HIV-1ADA virus. 25499264 3 18 theme resistance 557:566 arg1 development 568:578 CBA resistance development 553:578 CBA resistance development 553:578 Recently, also an N-glycan on the transmembrane envelope glycoprotein gp41 was shown to be deleted during CBA resistance development. 25499264 8 19 theme WT 1584:1585 arg1 virus 1596:1600 WT HIV-1ADA virus 1584:1600 WT HIV-1ADA virus 1584:1600 In contrast, N616Q gp41 mutant HIV-1ADA contained gp120 levels similar to the gp120 levels in WT HIV-1ADA virus. 25499264 1 20 theme antiretroviral 193:206 arg1 compounds 208:216 potent antiretroviral compounds 186:216 potent antiretroviral compounds that target the N-glycans on the HIV-1 envelope glycoproteins 186:278 BACKGROUND: Carbohydrate-binding agents (CBAs) are potent antiretroviral compounds that target the N-glycans on the HIV-1 envelope glycoproteins. 25499264 1 20 theme antiretroviral 193:206 arg1 BACKGROUND 135:144 BACKGROUND 135:144 BACKGROUND: Carbohydrate-binding agents (CBAs) are potent antiretroviral compounds that target the N-glycans on the HIV-1 envelope glycoproteins. 135:279 BACKGROUND: Carbohydrate-binding agents (CBAs) are potent antiretroviral compounds that target the N-glycans on the HIV-1 envelope glycoproteins. 25499264 1 20 theme antiretroviral 193:206 arg1 agents 168:173 Carbohydrate-binding agents 147:173 Carbohydrate-binding agents (CBAs) 147:180 BACKGROUND: Carbohydrate-binding agents (CBAs) are potent antiretroviral compounds that target the N-glycans on the HIV-1 envelope glycoproteins. 25499264 8 21 theme gp120 1540:1544 arg1 levels 1546:1551 gp120 levels 1540:1551 gp120 levels similar to the gp120 levels in WT HIV-1ADA virus 1540:1600 In contrast, N616Q gp41 mutant HIV-1ADA contained gp120 levels similar to the gp120 levels in WT HIV-1ADA virus. 25499264 13 22 dep particular 2171:2180 arg1 indispensable 2231:2243 indispensable 2231:2243 indispensable 2231:2243 CONCLUSIONS: We revealed the importance of some gp41 N-linked glycans, in particular the N616 glycan which was shown to be absolutely indispensable for the infectivity potential of several virus strains. 25499264 13 22 dep particular 2171:2180 arg1 glycan 2191:2196 the N616 glycan 2182:2196 particular the N616 glycan which was shown to be absolutely indispensable for the infectivity potential of several virus strains 2171:2298 CONCLUSIONS: We revealed the importance of some gp41 N-linked glycans, in particular the N616 glycan which was shown to be absolutely indispensable for the infectivity potential of several virus strains. 25499264 0 23 theme agents 127:132 arg1 effects 95:101 the suppressive effects 79:101 the suppressive effects of carbohydrate-binding agents 79:132 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. 25499264 4 24 theme CBAs 1000:1003 arg1 selection 987:995 a selection 985:995 a selection of CBAs 985:1003 RESULTS: We generated HIV-1 mutants lacking gp41 N-glycans and determined the influence of these glycan deletions on the viral phenotype (infectivity, CD4 binding, envelope glycoprotein incorporation in the viral particle and on the transfected cell, virus capture by DC-SIGN(+) cells and transmission of DC-SIGN-captured virions to CD4(+) T-lymphocytes) and on the phenotypic susceptibility of HIV-1 to a selection of CBAs. 25499264 11 25 theme glycans 1914:1920 arg1 presence 1893:1900 the concomitant presence 1877:1900 the concomitant presence of all gp41 glycans 1877:1920 However, the antiviral activity of CBAs is not dependent on the concomitant presence of all gp41 glycans. 25499264 6 26 theme X4-tropic 1221:1229 arg1 IIIB 1231:1234 the X4-tropic IIIB and NL4.3 strains 1217:1252 IIIB 1231:1234 In particular, lack of an intact N616 glycosylation site was shown to result in the loss of viral infectivity of several (i.e. the X4-tropic IIIB and NL4.3 strains, and the X4/R5-tropic HE strain), but not all (i.e. the R5-tropic ADA strain) studied HIV-1 strains. 25499264 4 27 theme DC-SIGN-captured 886:901 arg1 virions 903:909 DC-SIGN-captured virions 886:909 DC-SIGN-captured virions 886:909 RESULTS: We generated HIV-1 mutants lacking gp41 N-glycans and determined the influence of these glycan deletions on the viral phenotype (infectivity, CD4 binding, envelope glycoprotein incorporation in the viral particle and on the transfected cell, virus capture by DC-SIGN(+) cells and transmission of DC-SIGN-captured virions to CD4(+) T-lymphocytes) and on the phenotypic susceptibility of HIV-1 to a selection of CBAs. 25499264 12 28 theme gp41 1930:1933 arg1 deletions 1942:1950 Single gp41 glycan deletions 1923:1950 Single gp41 glycan deletions 1923:1950 Single gp41 glycan deletions had no marked effects on CBA susceptibility, whereas some combinations of two to three gp41 glycan-deletions had a minor effect on CBA activity. 25499264 12 29 dep three 2033:2037 arg1 to 2030:2031 to 2030:2031 to 2030:2031 Single gp41 glycan deletions had no marked effects on CBA susceptibility, whereas some combinations of two to three gp41 glycan-deletions had a minor effect on CBA activity. 25499264 14 30 theme CBA 2408:2410 arg1 susceptibility 2412:2425 CBA susceptibility 2408:2425 CBA susceptibility 2408:2425 In addition, we demonstrated that the deletion of up to three gp41 N-linked glycans only slightly affected CBA susceptibility. 25499264 6 31 theme glycosylation 1128:1140 arg1 site 1142:1145 an intact N616 glycosylation site 1113:1145 an intact N616 glycosylation site 1113:1145 In particular, lack of an intact N616 glycosylation site was shown to result in the loss of viral infectivity of several (i.e. the X4-tropic IIIB and NL4.3 strains, and the X4/R5-tropic HE strain), but not all (i.e. the R5-tropic ADA strain) studied HIV-1 strains. 25499264 14 32 link N-linked 2368:2375 arg1 glycans 2377:2383 up to three gp41 N-linked glycans 2351:2383 up to three gp41 N-linked glycans 2351:2383 In addition, we demonstrated that the deletion of up to three gp41 N-linked glycans only slightly affected CBA susceptibility. 25499264 0 33 theme virus 39:43 arg1 infectivity 45:55 virus infectivity 39:55 virus infectivity 39:55 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. 25499264 7 34 theme strains 1438:1444 arg1 envelope 1408:1415 the envelope 1404:1415 the envelope of N616Q mutant gp41 strains NL4.3, IIIB and HE 1404:1463 In accordance, we found that the gp120 levels in the envelope of N616Q mutant gp41 strains NL4.3, IIIB and HE were severely decreased. 25499264 4 35 theme phenotypic 947:956 arg1 susceptibility 958:971 the phenotypic susceptibility 943:971 the phenotypic susceptibility of HIV-1 to a selection of CBAs 943:1003 RESULTS: We generated HIV-1 mutants lacking gp41 N-glycans and determined the influence of these glycan deletions on the viral phenotype (infectivity, CD4 binding, envelope glycoprotein incorporation in the viral particle and on the transfected cell, virus capture by DC-SIGN(+) cells and transmission of DC-SIGN-captured virions to CD4(+) T-lymphocytes) and on the phenotypic susceptibility of HIV-1 to a selection of CBAs. 25499264 4 36 theme viral 702:706 arg1 phenotype 708:716 the viral phenotype 698:716 the viral phenotype (infectivity, CD4 binding, envelope glycoprotein incorporation in the viral particle and on the transfected cell, virus capture by DC-SIGN(+) cells and transmission of DC-SIGN-captured virions to CD4(+) T-lymphocytes) 698:934 RESULTS: We generated HIV-1 mutants lacking gp41 N-glycans and determined the influence of these glycan deletions on the viral phenotype (infectivity, CD4 binding, envelope glycoprotein incorporation in the viral particle and on the transfected cell, virus capture by DC-SIGN(+) cells and transmission of DC-SIGN-captured virions to CD4(+) T-lymphocytes) and on the phenotypic susceptibility of HIV-1 to a selection of CBAs. 25499264 7 37 theme mutant 1426:1431 arg1 HE 1462:1463 HE 1462:1463 HE 1462:1463 In accordance, we found that the gp120 levels in the envelope of N616Q mutant gp41 strains NL4.3, IIIB and HE were severely decreased. 25499264 7 37 theme mutant 1426:1431 arg1 strains 1438:1444 N616Q mutant gp41 strains NL4.3, IIIB and HE 1420:1463 N616Q mutant gp41 strains NL4.3, IIIB and HE 1420:1463 In accordance, we found that the gp120 levels in the envelope of N616Q mutant gp41 strains NL4.3, IIIB and HE were severely decreased. 25499264 7 37 theme mutant 1426:1431 arg1 IIIB 1453:1456 IIIB 1453:1456 IIIB 1453:1456 In accordance, we found that the gp120 levels in the envelope of N616Q mutant gp41 strains NL4.3, IIIB and HE were severely decreased. 25499264 7 37 theme mutant 1426:1431 arg1 NL4.3 1446:1450 NL4.3 1446:1450 NL4.3 1446:1450 In accordance, we found that the gp120 levels in the envelope of N616Q mutant gp41 strains NL4.3, IIIB and HE were severely decreased. 25499264 9 38 theme deleting 1617:1624 arg1 N-glycans 1640:1648 Concomitantly deleting multiple gp41 N-glycans 1603:1648 Concomitantly deleting multiple gp41 N-glycans 1603:1648 Concomitantly deleting multiple gp41 N-glycans was often highly detrimental for viral infectivity. 25499264 12 39 theme minor 2067:2071 arg1 effect 2073:2078 a minor effect 2065:2078 a minor effect 2065:2078 Single gp41 glycan deletions had no marked effects on CBA susceptibility, whereas some combinations of two to three gp41 glycan-deletions had a minor effect on CBA activity. 25499264 6 40 theme X4/R5-tropic 1263:1274 arg1 strain 1279:1284 the X4/R5-tropic HE strain 1259:1284 the X4/R5-tropic HE strain 1259:1284 In particular, lack of an intact N616 glycosylation site was shown to result in the loss of viral infectivity of several (i.e. the X4-tropic IIIB and NL4.3 strains, and the X4/R5-tropic HE strain), but not all (i.e. the R5-tropic ADA strain) studied HIV-1 strains. 25499264 4 41 from incorporation 767:779 arg1 cell 826:829 the transfected cell 810:829 the transfected cell 810:829 RESULTS: We generated HIV-1 mutants lacking gp41 N-glycans and determined the influence of these glycan deletions on the viral phenotype (infectivity, CD4 binding, envelope glycoprotein incorporation in the viral particle and on the transfected cell, virus capture by DC-SIGN(+) cells and transmission of DC-SIGN-captured virions to CD4(+) T-lymphocytes) and on the phenotypic susceptibility of HIV-1 to a selection of CBAs. 25499264 4 41 from incorporation 767:779 arg1 particle 794:801 the viral particle 784:801 the viral particle 784:801 RESULTS: We generated HIV-1 mutants lacking gp41 N-glycans and determined the influence of these glycan deletions on the viral phenotype (infectivity, CD4 binding, envelope glycoprotein incorporation in the viral particle and on the transfected cell, virus capture by DC-SIGN(+) cells and transmission of DC-SIGN-captured virions to CD4(+) T-lymphocytes) and on the phenotypic susceptibility of HIV-1 to a selection of CBAs. 25499264 13 42 theme infectivity 2253:2263 arg1 potential 2265:2273 the infectivity potential 2249:2273 the infectivity potential of several virus strains 2249:2298 CONCLUSIONS: We revealed the importance of some gp41 N-linked glycans, in particular the N616 glycan which was shown to be absolutely indispensable for the infectivity potential of several virus strains. 25499264 9 43 theme gp41 1635:1638 arg1 N-glycans 1640:1648 Concomitantly deleting multiple gp41 N-glycans 1603:1648 Concomitantly deleting multiple gp41 N-glycans 1603:1648 Concomitantly deleting multiple gp41 N-glycans was often highly detrimental for viral infectivity. 25499264 12 44 theme CBA 2083:2085 arg1 activity 2087:2094 CBA activity 2083:2094 CBA activity 2083:2094 Single gp41 glycan deletions had no marked effects on CBA susceptibility, whereas some combinations of two to three gp41 glycan-deletions had a minor effect on CBA activity. 25499264 2 45 theme glycans 395:401 arg1 deletion 365:372 the deletion 361:372 the deletion of multiple N-linked glycans of the surface envelope glycoprotein gp120 361:444 The development of phenotypic resistance to CBAs by the virus is accompanied by the deletion of multiple N-linked glycans of the surface envelope glycoprotein gp120. 25499264 0 46 theme suppressive 83:93 arg1 effects 95:101 the suppressive effects 79:101 the suppressive effects of carbohydrate-binding agents 79:132 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. 25499264 13 47 link N-linked 2150:2157 arg1 glycans 2159:2165 some gp41 N-linked glycans 2140:2165 some gp41 N-linked glycans 2140:2165 CONCLUSIONS: We revealed the importance of some gp41 N-linked glycans, in particular the N616 glycan which was shown to be absolutely indispensable for the infectivity potential of several virus strains. 25499264 12 48 theme gp41 2039:2042 arg1 glycan-deletions 2044:2059 two to three gp41 glycan-deletions 2026:2059 two to three gp41 glycan-deletions 2026:2059 Single gp41 glycan deletions had no marked effects on CBA susceptibility, whereas some combinations of two to three gp41 glycan-deletions had a minor effect on CBA activity. 25499264 2 49 theme multiple 377:384 arg1 glycans 395:401 multiple N-linked glycans 377:401 multiple N-linked glycans of the surface envelope glycoprotein gp120 377:444 The development of phenotypic resistance to CBAs by the virus is accompanied by the deletion of multiple N-linked glycans of the surface envelope glycoprotein gp120. 25499264 6 50 theme ADA 1320:1322 arg1 strain 1324:1329 the R5-tropic ADA strain 1306:1329 the R5-tropic ADA strain 1306:1329 In particular, lack of an intact N616 glycosylation site was shown to result in the loss of viral infectivity of several (i.e. the X4-tropic IIIB and NL4.3 strains, and the X4/R5-tropic HE strain), but not all (i.e. the R5-tropic ADA strain) studied HIV-1 strains. 25499264 1 51 gly glycoproteins 266:278 arg1 glycoproteins 266:278 the HIV-1 envelope glycoproteins 247:278 the HIV-1 envelope glycoproteins 247:278 BACKGROUND: Carbohydrate-binding agents (CBAs) are potent antiretroviral compounds that target the N-glycans on the HIV-1 envelope glycoproteins. 25499264 2 52 theme gp120 440:444 arg1 glycans 395:401 multiple N-linked glycans 377:401 multiple N-linked glycans of the surface envelope glycoprotein gp120 377:444 The development of phenotypic resistance to CBAs by the virus is accompanied by the deletion of multiple N-linked glycans of the surface envelope glycoprotein gp120. 25499264 4 53 theme envelope 745:752 arg1 incorporation 767:779 envelope glycoprotein incorporation 745:779 envelope glycoprotein incorporation in the viral particle and on the transfected cell 745:829 RESULTS: We generated HIV-1 mutants lacking gp41 N-glycans and determined the influence of these glycan deletions on the viral phenotype (infectivity, CD4 binding, envelope glycoprotein incorporation in the viral particle and on the transfected cell, virus capture by DC-SIGN(+) cells and transmission of DC-SIGN-captured virions to CD4(+) T-lymphocytes) and on the phenotypic susceptibility of HIV-1 to a selection of CBAs. 25499264 4 53 theme envelope 745:752 arg1 infectivity 719:729 infectivity 719:729 infectivity 719:729 RESULTS: We generated HIV-1 mutants lacking gp41 N-glycans and determined the influence of these glycan deletions on the viral phenotype (infectivity, CD4 binding, envelope glycoprotein incorporation in the viral particle and on the transfected cell, virus capture by DC-SIGN(+) cells and transmission of DC-SIGN-captured virions to CD4(+) T-lymphocytes) and on the phenotypic susceptibility of HIV-1 to a selection of CBAs. 25499264 2 54 theme envelope 418:425 arg1 gp120 440:444 the surface envelope glycoprotein gp120 406:444 the surface envelope glycoprotein gp120 406:444 The development of phenotypic resistance to CBAs by the virus is accompanied by the deletion of multiple N-linked glycans of the surface envelope glycoprotein gp120. 25499264 4 55 dep phenotype 708:716 arg1 incorporation 767:779 envelope glycoprotein incorporation 745:779 envelope glycoprotein incorporation in the viral particle and on the transfected cell 745:829 RESULTS: We generated HIV-1 mutants lacking gp41 N-glycans and determined the influence of these glycan deletions on the viral phenotype (infectivity, CD4 binding, envelope glycoprotein incorporation in the viral particle and on the transfected cell, virus capture by DC-SIGN(+) cells and transmission of DC-SIGN-captured virions to CD4(+) T-lymphocytes) and on the phenotypic susceptibility of HIV-1 to a selection of CBAs. 25499264 4 55 dep phenotype 708:716 arg1 infectivity 719:729 infectivity 719:729 infectivity 719:729 RESULTS: We generated HIV-1 mutants lacking gp41 N-glycans and determined the influence of these glycan deletions on the viral phenotype (infectivity, CD4 binding, envelope glycoprotein incorporation in the viral particle and on the transfected cell, virus capture by DC-SIGN(+) cells and transmission of DC-SIGN-captured virions to CD4(+) T-lymphocytes) and on the phenotypic susceptibility of HIV-1 to a selection of CBAs. 25499264 4 55 dep phenotype 708:716 arg1 binding 736:742 CD4 binding 732:742 CD4 binding 732:742 RESULTS: We generated HIV-1 mutants lacking gp41 N-glycans and determined the influence of these glycan deletions on the viral phenotype (infectivity, CD4 binding, envelope glycoprotein incorporation in the viral particle and on the transfected cell, virus capture by DC-SIGN(+) cells and transmission of DC-SIGN-captured virions to CD4(+) T-lymphocytes) and on the phenotypic susceptibility of HIV-1 to a selection of CBAs. 25499264 4 55 dep phenotype 708:716 arg1 capture 838:844 virus capture 832:844 virus capture by DC-SIGN(+) cells and transmission of DC-SIGN-captured virions to CD4(+) T-lymphocytes 832:933 RESULTS: We generated HIV-1 mutants lacking gp41 N-glycans and determined the influence of these glycan deletions on the viral phenotype (infectivity, CD4 binding, envelope glycoprotein incorporation in the viral particle and on the transfected cell, virus capture by DC-SIGN(+) cells and transmission of DC-SIGN-captured virions to CD4(+) T-lymphocytes) and on the phenotypic susceptibility of HIV-1 to a selection of CBAs. 25499264 10 56 theme plasmon 1716:1722 arg1 technology 1734:1743 surface plasmon resonance technology 1708:1743 surface plasmon resonance technology 1708:1743 Using surface plasmon resonance technology we showed that CBAs have a pronounced affinity for both gp120 and gp41. 25499264 4 57 theme transfected 814:824 arg1 cell 826:829 the transfected cell 810:829 the transfected cell 810:829 RESULTS: We generated HIV-1 mutants lacking gp41 N-glycans and determined the influence of these glycan deletions on the viral phenotype (infectivity, CD4 binding, envelope glycoprotein incorporation in the viral particle and on the transfected cell, virus capture by DC-SIGN(+) cells and transmission of DC-SIGN-captured virions to CD4(+) T-lymphocytes) and on the phenotypic susceptibility of HIV-1 to a selection of CBAs. 25499264 7 58 theme gp120 1388:1392 arg1 levels 1394:1399 the gp120 levels 1384:1399 the gp120 levels in the envelope of N616Q mutant gp41 strains NL4.3, IIIB and HE 1384:1463 In accordance, we found that the gp120 levels in the envelope of N616Q mutant gp41 strains NL4.3, IIIB and HE were severely decreased. 25499264 6 59 dep studied 1332:1338 arg1 several 1203:1209 several 1203:1209 several 1203:1209 In particular, lack of an intact N616 glycosylation site was shown to result in the loss of viral infectivity of several (i.e. the X4-tropic IIIB and NL4.3 strains, and the X4/R5-tropic HE strain), but not all (i.e. the R5-tropic ADA strain) studied HIV-1 strains. 25499264 6 59 dep studied 1332:1338 arg1 all 1296:1298 all 1296:1298 all 1296:1298 In particular, lack of an intact N616 glycosylation site was shown to result in the loss of viral infectivity of several (i.e. the X4-tropic IIIB and NL4.3 strains, and the X4/R5-tropic HE strain), but not all (i.e. the R5-tropic ADA strain) studied HIV-1 strains. 25499264 2 60 link N-linked 386:393 arg1 glycans 395:401 multiple N-linked glycans 377:401 multiple N-linked glycans of the surface envelope glycoprotein gp120 377:444 The development of phenotypic resistance to CBAs by the virus is accompanied by the deletion of multiple N-linked glycans of the surface envelope glycoprotein gp120. 25499264 3 61 theme transmembrane 481:493 arg1 glycoprotein 504:515 the transmembrane envelope glycoprotein gp41 477:520 the transmembrane envelope glycoprotein gp41 477:520 Recently, also an N-glycan on the transmembrane envelope glycoprotein gp41 was shown to be deleted during CBA resistance development. 25499264 3 62 from N-glycan 465:472 arg1 glycoprotein 504:515 the transmembrane envelope glycoprotein gp41 477:520 the transmembrane envelope glycoprotein gp41 477:520 Recently, also an N-glycan on the transmembrane envelope glycoprotein gp41 was shown to be deleted during CBA resistance development. 25499264 4 63 theme HIV-1 603:607 arg1 mutants 609:615 HIV-1 mutants 603:615 HIV-1 mutants lacking gp41 N-glycans 603:638 RESULTS: We generated HIV-1 mutants lacking gp41 N-glycans and determined the influence of these glycan deletions on the viral phenotype (infectivity, CD4 binding, envelope glycoprotein incorporation in the viral particle and on the transfected cell, virus capture by DC-SIGN(+) cells and transmission of DC-SIGN-captured virions to CD4(+) T-lymphocytes) and on the phenotypic susceptibility of HIV-1 to a selection of CBAs. 25499264 6 64 theme R5-tropic 1310:1318 arg1 strain 1324:1329 the R5-tropic ADA strain 1306:1329 the R5-tropic ADA strain 1306:1329 In particular, lack of an intact N616 glycosylation site was shown to result in the loss of viral infectivity of several (i.e. the X4-tropic IIIB and NL4.3 strains, and the X4/R5-tropic HE strain), but not all (i.e. the R5-tropic ADA strain) studied HIV-1 strains. 25499264 8 65 from levels 1574:1579 arg1 virus 1596:1600 WT HIV-1ADA virus 1584:1600 WT HIV-1ADA virus 1584:1600 In contrast, N616Q gp41 mutant HIV-1ADA contained gp120 levels similar to the gp120 levels in WT HIV-1ADA virus. 25499264 8 66 theme N616Q 1503:1507 arg1 HIV-1ADA 1521:1528 N616Q gp41 mutant HIV-1ADA 1503:1528 N616Q gp41 mutant HIV-1ADA 1503:1528 In contrast, N616Q gp41 mutant HIV-1ADA contained gp120 levels similar to the gp120 levels in WT HIV-1ADA virus. 25499264 10 67 dep showed 1748:1753 arg1 Using 1702:1706 Using 1702:1706 Using surface plasmon resonance technology 1702:1743 Using surface plasmon resonance technology we showed that CBAs have a pronounced affinity for both gp120 and gp41. 25499264 6 68 theme HIV-1 1340:1344 arg1 strains 1346:1352 several (i.e. the X4-tropic IIIB and NL4.3 strains, and the X4/R5-tropic HE strain), but not all (i.e. the R5-tropic ADA strain) studied HIV-1 strains 1203:1352 several (i.e. the X4-tropic IIIB and NL4.3 strains, and the X4/R5-tropic HE strain), but not all (i.e. the R5-tropic ADA strain) studied HIV-1 strains 1203:1352 In particular, lack of an intact N616 glycosylation site was shown to result in the loss of viral infectivity of several (i.e. the X4-tropic IIIB and NL4.3 strains, and the X4/R5-tropic HE strain), but not all (i.e. the R5-tropic ADA strain) studied HIV-1 strains. 25499264 1 69 theme envelope 257:264 arg1 glycoproteins 266:278 the HIV-1 envelope glycoproteins 247:278 the HIV-1 envelope glycoproteins 247:278 BACKGROUND: Carbohydrate-binding agents (CBAs) are potent antiretroviral compounds that target the N-glycans on the HIV-1 envelope glycoproteins. 25499264 7 70 from levels 1394:1399 arg1 envelope 1408:1415 the envelope 1404:1415 the envelope of N616Q mutant gp41 strains NL4.3, IIIB and HE 1404:1463 In accordance, we found that the gp120 levels in the envelope of N616Q mutant gp41 strains NL4.3, IIIB and HE were severely decreased. 25499264 6 71 theme viral 1182:1186 arg1 infectivity 1188:1198 viral infectivity 1182:1198 viral infectivity of several (i.e. the X4-tropic IIIB and NL4.3 strains, and the X4/R5-tropic HE strain), but not all (i.e. the R5-tropic ADA strain) studied HIV-1 strains 1182:1352 In particular, lack of an intact N616 glycosylation site was shown to result in the loss of viral infectivity of several (i.e. the X4-tropic IIIB and NL4.3 strains, and the X4/R5-tropic HE strain), but not all (i.e. the R5-tropic ADA strain) studied HIV-1 strains. 25499264 12 72 theme CBA 1977:1979 arg1 susceptibility 1981:1994 CBA susceptibility 1977:1994 CBA susceptibility 1977:1994 Single gp41 glycan deletions had no marked effects on CBA susceptibility, whereas some combinations of two to three gp41 glycan-deletions had a minor effect on CBA activity. 25499264 13 73 theme N-linked 2150:2157 arg1 glycans 2159:2165 some gp41 N-linked glycans 2140:2165 some gp41 N-linked glycans 2140:2165 CONCLUSIONS: We revealed the importance of some gp41 N-linked glycans, in particular the N616 glycan which was shown to be absolutely indispensable for the infectivity potential of several virus strains. 25499264 6 74 dep several 1203:1209 arg1 IIIB 1231:1234 the X4-tropic IIIB and NL4.3 strains 1217:1252 IIIB 1231:1234 In particular, lack of an intact N616 glycosylation site was shown to result in the loss of viral infectivity of several (i.e. the X4-tropic IIIB and NL4.3 strains, and the X4/R5-tropic HE strain), but not all (i.e. the R5-tropic ADA strain) studied HIV-1 strains. 25499264 6 74 dep several 1203:1209 arg1 strains 1246:1252 the X4-tropic IIIB and NL4.3 strains 1217:1252 strains 1246:1252 In particular, lack of an intact N616 glycosylation site was shown to result in the loss of viral infectivity of several (i.e. the X4-tropic IIIB and NL4.3 strains, and the X4/R5-tropic HE strain), but not all (i.e. the R5-tropic ADA strain) studied HIV-1 strains. 25499264 6 74 dep several 1203:1209 arg1 strain 1279:1284 the X4/R5-tropic HE strain 1259:1284 the X4/R5-tropic HE strain 1259:1284 In particular, lack of an intact N616 glycosylation site was shown to result in the loss of viral infectivity of several (i.e. the X4-tropic IIIB and NL4.3 strains, and the X4/R5-tropic HE strain), but not all (i.e. the R5-tropic ADA strain) studied HIV-1 strains. 25499264 4 75 theme virus 832:836 arg1 infectivity 719:729 infectivity 719:729 infectivity 719:729 RESULTS: We generated HIV-1 mutants lacking gp41 N-glycans and determined the influence of these glycan deletions on the viral phenotype (infectivity, CD4 binding, envelope glycoprotein incorporation in the viral particle and on the transfected cell, virus capture by DC-SIGN(+) cells and transmission of DC-SIGN-captured virions to CD4(+) T-lymphocytes) and on the phenotypic susceptibility of HIV-1 to a selection of CBAs. 25499264 4 75 theme virus 832:836 arg1 capture 838:844 virus capture 832:844 virus capture by DC-SIGN(+) cells and transmission of DC-SIGN-captured virions to CD4(+) T-lymphocytes 832:933 RESULTS: We generated HIV-1 mutants lacking gp41 N-glycans and determined the influence of these glycan deletions on the viral phenotype (infectivity, CD4 binding, envelope glycoprotein incorporation in the viral particle and on the transfected cell, virus capture by DC-SIGN(+) cells and transmission of DC-SIGN-captured virions to CD4(+) T-lymphocytes) and on the phenotypic susceptibility of HIV-1 to a selection of CBAs. 25499264 12 76 theme marked 1959:1964 arg1 effects 1966:1972 no marked effects 1956:1972 no marked effects on CBA susceptibility 1956:1994 Single gp41 glycan deletions had no marked effects on CBA susceptibility, whereas some combinations of two to three gp41 glycan-deletions had a minor effect on CBA activity. 25499264 4 77 from influence 659:667 arg1 susceptibility 958:971 the phenotypic susceptibility 943:971 the phenotypic susceptibility of HIV-1 to a selection of CBAs 943:1003 RESULTS: We generated HIV-1 mutants lacking gp41 N-glycans and determined the influence of these glycan deletions on the viral phenotype (infectivity, CD4 binding, envelope glycoprotein incorporation in the viral particle and on the transfected cell, virus capture by DC-SIGN(+) cells and transmission of DC-SIGN-captured virions to CD4(+) T-lymphocytes) and on the phenotypic susceptibility of HIV-1 to a selection of CBAs. 25499264 4 77 from influence 659:667 arg1 phenotype 708:716 the viral phenotype 698:716 the viral phenotype (infectivity, CD4 binding, envelope glycoprotein incorporation in the viral particle and on the transfected cell, virus capture by DC-SIGN(+) cells and transmission of DC-SIGN-captured virions to CD4(+) T-lymphocytes) 698:934 RESULTS: We generated HIV-1 mutants lacking gp41 N-glycans and determined the influence of these glycan deletions on the viral phenotype (infectivity, CD4 binding, envelope glycoprotein incorporation in the viral particle and on the transfected cell, virus capture by DC-SIGN(+) cells and transmission of DC-SIGN-captured virions to CD4(+) T-lymphocytes) and on the phenotypic susceptibility of HIV-1 to a selection of CBAs. 25499264 0 78 theme carbohydrate-binding 106:125 arg1 agents 127:132 carbohydrate-binding agents 106:132 carbohydrate-binding agents 106:132 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. 25499264 2 79 theme resistance 311:320 arg1 development 285:295 The development 281:295 The development of phenotypic resistance to CBAs by the virus 281:341 The development of phenotypic resistance to CBAs by the virus is accompanied by the deletion of multiple N-linked glycans of the surface envelope glycoprotein gp120. 25499264 8 80 theme gp120 1568:1572 arg1 levels 1574:1579 the gp120 levels 1564:1579 the gp120 levels in WT HIV-1ADA virus 1564:1600 In contrast, N616Q gp41 mutant HIV-1ADA contained gp120 levels similar to the gp120 levels in WT HIV-1ADA virus. 25499264 1 81 theme potent 186:191 arg1 compounds 208:216 potent antiretroviral compounds 186:216 potent antiretroviral compounds that target the N-glycans on the HIV-1 envelope glycoproteins 186:278 BACKGROUND: Carbohydrate-binding agents (CBAs) are potent antiretroviral compounds that target the N-glycans on the HIV-1 envelope glycoproteins. 25499264 1 81 theme potent 186:191 arg1 BACKGROUND 135:144 BACKGROUND 135:144 BACKGROUND: Carbohydrate-binding agents (CBAs) are potent antiretroviral compounds that target the N-glycans on the HIV-1 envelope glycoproteins. 135:279 BACKGROUND: Carbohydrate-binding agents (CBAs) are potent antiretroviral compounds that target the N-glycans on the HIV-1 envelope glycoproteins. 25499264 1 81 theme potent 186:191 arg1 agents 168:173 Carbohydrate-binding agents 147:173 Carbohydrate-binding agents (CBAs) 147:180 BACKGROUND: Carbohydrate-binding agents (CBAs) are potent antiretroviral compounds that target the N-glycans on the HIV-1 envelope glycoproteins. 25499264 4 82 theme virions 903:909 arg1 transmission 870:881 transmission 870:881 transmission of DC-SIGN-captured virions to CD4(+) T-lymphocytes 870:933 RESULTS: We generated HIV-1 mutants lacking gp41 N-glycans and determined the influence of these glycan deletions on the viral phenotype (infectivity, CD4 binding, envelope glycoprotein incorporation in the viral particle and on the transfected cell, virus capture by DC-SIGN(+) cells and transmission of DC-SIGN-captured virions to CD4(+) T-lymphocytes) and on the phenotypic susceptibility of HIV-1 to a selection of CBAs. 25499264 4 82 theme virions 903:909 arg1 cells 860:864 DC-SIGN(+) cells 849:864 DC-SIGN(+) cells 849:864 RESULTS: We generated HIV-1 mutants lacking gp41 N-glycans and determined the influence of these glycan deletions on the viral phenotype (infectivity, CD4 binding, envelope glycoprotein incorporation in the viral particle and on the transfected cell, virus capture by DC-SIGN(+) cells and transmission of DC-SIGN-captured virions to CD4(+) T-lymphocytes) and on the phenotypic susceptibility of HIV-1 to a selection of CBAs. 25499264 0 83 from susceptibility 61:74 arg1 infectivity 45:55 virus infectivity 39:55 virus infectivity 39:55 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. 25499264 12 84 theme glycan 1935:1940 arg1 deletions 1942:1950 Single gp41 glycan deletions 1923:1950 Single gp41 glycan deletions 1923:1950 Single gp41 glycan deletions had no marked effects on CBA susceptibility, whereas some combinations of two to three gp41 glycan-deletions had a minor effect on CBA activity. 25499264 6 85 theme NL4.3 1240:1244 arg1 strains 1246:1252 the X4-tropic IIIB and NL4.3 strains 1217:1252 strains 1246:1252 In particular, lack of an intact N616 glycosylation site was shown to result in the loss of viral infectivity of several (i.e. the X4-tropic IIIB and NL4.3 strains, and the X4/R5-tropic HE strain), but not all (i.e. the R5-tropic ADA strain) studied HIV-1 strains. 25499264 7 86 dep strains 1438:1444 arg1 HE 1462:1463 HE 1462:1463 HE 1462:1463 In accordance, we found that the gp120 levels in the envelope of N616Q mutant gp41 strains NL4.3, IIIB and HE were severely decreased. 25499264 7 86 dep strains 1438:1444 arg1 strains 1438:1444 N616Q mutant gp41 strains NL4.3, IIIB and HE 1420:1463 N616Q mutant gp41 strains NL4.3, IIIB and HE 1420:1463 In accordance, we found that the gp120 levels in the envelope of N616Q mutant gp41 strains NL4.3, IIIB and HE were severely decreased. 25499264 7 86 dep strains 1438:1444 arg1 IIIB 1453:1456 IIIB 1453:1456 IIIB 1453:1456 In accordance, we found that the gp120 levels in the envelope of N616Q mutant gp41 strains NL4.3, IIIB and HE were severely decreased. 25499264 7 86 dep strains 1438:1444 arg1 NL4.3 1446:1450 NL4.3 1446:1450 NL4.3 1446:1450 In accordance, we found that the gp120 levels in the envelope of N616Q mutant gp41 strains NL4.3, IIIB and HE were severely decreased. 25499264 4 87 theme CD4 914:916 arg1 T-lymphocytes 921:933 CD4(+) T-lymphocytes 914:933 CD4(+) T-lymphocytes 914:933 RESULTS: We generated HIV-1 mutants lacking gp41 N-glycans and determined the influence of these glycan deletions on the viral phenotype (infectivity, CD4 binding, envelope glycoprotein incorporation in the viral particle and on the transfected cell, virus capture by DC-SIGN(+) cells and transmission of DC-SIGN-captured virions to CD4(+) T-lymphocytes) and on the phenotypic susceptibility of HIV-1 to a selection of CBAs. 25499264 1 88 from N-glycans 234:242 arg1 glycoproteins 266:278 the HIV-1 envelope glycoproteins 247:278 the HIV-1 envelope glycoproteins 247:278 BACKGROUND: Carbohydrate-binding agents (CBAs) are potent antiretroviral compounds that target the N-glycans on the HIV-1 envelope glycoproteins. 25499264 8 89 theme HIV-1ADA 1587:1594 arg1 virus 1596:1600 WT HIV-1ADA virus 1584:1600 WT HIV-1ADA virus 1584:1600 In contrast, N616Q gp41 mutant HIV-1ADA contained gp120 levels similar to the gp120 levels in WT HIV-1ADA virus. 25499264 13 90 theme strains 2292:2298 arg1 potential 2265:2273 the infectivity potential 2249:2273 the infectivity potential of several virus strains 2249:2298 CONCLUSIONS: We revealed the importance of some gp41 N-linked glycans, in particular the N616 glycan which was shown to be absolutely indispensable for the infectivity potential of several virus strains. 25499264 11 91 theme antiviral 1830:1838 arg1 dependent 1864:1872 dependent 1864:1872 dependent 1864:1872 However, the antiviral activity of CBAs is not dependent on the concomitant presence of all gp41 glycans. 25499264 11 91 theme antiviral 1830:1838 arg1 activity 1840:1847 the antiviral activity 1826:1847 the antiviral activity of CBAs 1826:1855 However, the antiviral activity of CBAs is not dependent on the concomitant presence of all gp41 glycans. 25499264 3 92 theme CBA 553:555 arg1 development 568:578 CBA resistance development 553:578 CBA resistance development 553:578 Recently, also an N-glycan on the transmembrane envelope glycoprotein gp41 was shown to be deleted during CBA resistance development. 25499264 14 93 dep three 2357:2361 arg1 to 2354:2355 to 2354:2355 to 2354:2355 In addition, we demonstrated that the deletion of up to three gp41 N-linked glycans only slightly affected CBA susceptibility. 25499264 6 94 theme site 1142:1145 arg1 lack 1105:1108 lack 1105:1108 lack of an intact N616 glycosylation site 1105:1145 In particular, lack of an intact N616 glycosylation site was shown to result in the loss of viral infectivity of several (i.e. the X4-tropic IIIB and NL4.3 strains, and the X4/R5-tropic HE strain), but not all (i.e. the R5-tropic ADA strain) studied HIV-1 strains. 25499264 12 95 theme Single 1923:1928 arg1 deletions 1942:1950 Single gp41 glycan deletions 1923:1950 Single gp41 glycan deletions 1923:1950 Single gp41 glycan deletions had no marked effects on CBA susceptibility, whereas some combinations of two to three gp41 glycan-deletions had a minor effect on CBA activity. 25499264 4 96 gly glycoprotein 754:765 arg1 glycoprotein 754:765 envelope glycoprotein incorporation 745:779 envelope glycoprotein incorporation in the viral particle and on the transfected cell 745:829 RESULTS: We generated HIV-1 mutants lacking gp41 N-glycans and determined the influence of these glycan deletions on the viral phenotype (infectivity, CD4 binding, envelope glycoprotein incorporation in the viral particle and on the transfected cell, virus capture by DC-SIGN(+) cells and transmission of DC-SIGN-captured virions to CD4(+) T-lymphocytes) and on the phenotypic susceptibility of HIV-1 to a selection of CBAs. 25499264 7 97 theme gp41 1433:1436 arg1 HE 1462:1463 HE 1462:1463 HE 1462:1463 In accordance, we found that the gp120 levels in the envelope of N616Q mutant gp41 strains NL4.3, IIIB and HE were severely decreased. 25499264 7 97 theme gp41 1433:1436 arg1 strains 1438:1444 N616Q mutant gp41 strains NL4.3, IIIB and HE 1420:1463 N616Q mutant gp41 strains NL4.3, IIIB and HE 1420:1463 In accordance, we found that the gp120 levels in the envelope of N616Q mutant gp41 strains NL4.3, IIIB and HE were severely decreased. 25499264 7 97 theme gp41 1433:1436 arg1 IIIB 1453:1456 IIIB 1453:1456 IIIB 1453:1456 In accordance, we found that the gp120 levels in the envelope of N616Q mutant gp41 strains NL4.3, IIIB and HE were severely decreased. 25499264 7 97 theme gp41 1433:1436 arg1 NL4.3 1446:1450 NL4.3 1446:1450 NL4.3 1446:1450 In accordance, we found that the gp120 levels in the envelope of N616Q mutant gp41 strains NL4.3, IIIB and HE were severely decreased. 25499264 12 98 contain had 2061:2063 arg2 effect 2073:2078 a minor effect 2065:2078 a minor effect 2065:2078 Single gp41 glycan deletions had no marked effects on CBA susceptibility, whereas some combinations of two to three gp41 glycan-deletions had a minor effect on CBA activity. 25499264 12 98 contain had 2061:2063 arg1 combinations 2010:2021 some combinations 2005:2021 some combinations of two to three gp41 glycan-deletions 2005:2059 Single gp41 glycan deletions had no marked effects on CBA susceptibility, whereas some combinations of two to three gp41 glycan-deletions had a minor effect on CBA activity. 25499264 6 99 theme N616 1123:1126 arg1 site 1142:1145 an intact N616 glycosylation site 1113:1145 an intact N616 glycosylation site 1113:1145 In particular, lack of an intact N616 glycosylation site was shown to result in the loss of viral infectivity of several (i.e. the X4-tropic IIIB and NL4.3 strains, and the X4/R5-tropic HE strain), but not all (i.e. the R5-tropic ADA strain) studied HIV-1 strains. 25499264 4 100 theme deletions 685:693 arg1 influence 659:667 the influence 655:667 the influence of these glycan deletions on the viral phenotype (infectivity, CD4 binding, envelope glycoprotein incorporation in the viral particle and on the transfected cell, virus capture by DC-SIGN(+) cells and transmission of DC-SIGN-captured virions to CD4(+) T-lymphocytes) and on the phenotypic susceptibility of HIV-1 to a selection of CBAs 655:1003 RESULTS: We generated HIV-1 mutants lacking gp41 N-glycans and determined the influence of these glycan deletions on the viral phenotype (infectivity, CD4 binding, envelope glycoprotein incorporation in the viral particle and on the transfected cell, virus capture by DC-SIGN(+) cells and transmission of DC-SIGN-captured virions to CD4(+) T-lymphocytes) and on the phenotypic susceptibility of HIV-1 to a selection of CBAs. 25499264 14 101 theme glycans 2377:2383 arg1 deletion 2339:2346 the deletion 2335:2346 the deletion of up to three gp41 N-linked glycans 2335:2383 In addition, we demonstrated that the deletion of up to three gp41 N-linked glycans only slightly affected CBA susceptibility. 25499264 1 102 theme Carbohydrate-binding 147:166 arg1 compounds 208:216 potent antiretroviral compounds 186:216 potent antiretroviral compounds that target the N-glycans on the HIV-1 envelope glycoproteins 186:278 BACKGROUND: Carbohydrate-binding agents (CBAs) are potent antiretroviral compounds that target the N-glycans on the HIV-1 envelope glycoproteins. 25499264 1 102 theme Carbohydrate-binding 147:166 arg1 CBAs 176:179 CBAs 176:179 CBAs 176:179 BACKGROUND: Carbohydrate-binding agents (CBAs) are potent antiretroviral compounds that target the N-glycans on the HIV-1 envelope glycoproteins. 25499264 1 102 theme Carbohydrate-binding 147:166 arg1 BACKGROUND 135:144 BACKGROUND 135:144 BACKGROUND: Carbohydrate-binding agents (CBAs) are potent antiretroviral compounds that target the N-glycans on the HIV-1 envelope glycoproteins. 135:279 BACKGROUND: Carbohydrate-binding agents (CBAs) are potent antiretroviral compounds that target the N-glycans on the HIV-1 envelope glycoproteins. 25499264 1 102 theme Carbohydrate-binding 147:166 arg1 agents 168:173 Carbohydrate-binding agents 147:173 Carbohydrate-binding agents (CBAs) 147:180 BACKGROUND: Carbohydrate-binding agents (CBAs) are potent antiretroviral compounds that target the N-glycans on the HIV-1 envelope glycoproteins. 25499264 7 103 theme N616Q 1420:1424 arg1 HE 1462:1463 HE 1462:1463 HE 1462:1463 In accordance, we found that the gp120 levels in the envelope of N616Q mutant gp41 strains NL4.3, IIIB and HE were severely decreased. 25499264 7 103 theme N616Q 1420:1424 arg1 strains 1438:1444 N616Q mutant gp41 strains NL4.3, IIIB and HE 1420:1463 N616Q mutant gp41 strains NL4.3, IIIB and HE 1420:1463 In accordance, we found that the gp120 levels in the envelope of N616Q mutant gp41 strains NL4.3, IIIB and HE were severely decreased. 25499264 7 103 theme N616Q 1420:1424 arg1 IIIB 1453:1456 IIIB 1453:1456 IIIB 1453:1456 In accordance, we found that the gp120 levels in the envelope of N616Q mutant gp41 strains NL4.3, IIIB and HE were severely decreased. 25499264 7 103 theme N616Q 1420:1424 arg1 NL4.3 1446:1450 NL4.3 1446:1450 NL4.3 1446:1450 In accordance, we found that the gp120 levels in the envelope of N616Q mutant gp41 strains NL4.3, IIIB and HE were severely decreased. 25499264 0 104 from role 4:7 arg1 infectivity 45:55 virus infectivity 39:55 virus infectivity 39:55 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. 25499264 6 105 theme HE 1276:1277 arg1 strain 1279:1284 the X4/R5-tropic HE strain 1259:1284 the X4/R5-tropic HE strain 1259:1284 In particular, lack of an intact N616 glycosylation site was shown to result in the loss of viral infectivity of several (i.e. the X4-tropic IIIB and NL4.3 strains, and the X4/R5-tropic HE strain), but not all (i.e. the R5-tropic ADA strain) studied HIV-1 strains. 25499264 5 106 theme virus 1083:1087 arg1 infectivity 1064:1074 the infectivity 1060:1074 the infectivity of the virus 1060:1087 It was shown that some gp41 N-glycans are crucial for the infectivity of the virus. 25499264 12 107 from effects 1966:1972 arg1 susceptibility 1981:1994 CBA susceptibility 1977:1994 CBA susceptibility 1977:1994 Single gp41 glycan deletions had no marked effects on CBA susceptibility, whereas some combinations of two to three gp41 glycan-deletions had a minor effect on CBA activity. 25499264 2 108 theme phenotypic 300:309 arg1 resistance 311:320 phenotypic resistance 300:320 phenotypic resistance to CBAs 300:328 The development of phenotypic resistance to CBAs by the virus is accompanied by the deletion of multiple N-linked glycans of the surface envelope glycoprotein gp120. 25499264 14 109 theme N-linked 2368:2375 arg1 glycans 2377:2383 up to three gp41 N-linked glycans 2351:2383 up to three gp41 N-linked glycans 2351:2383 In addition, we demonstrated that the deletion of up to three gp41 N-linked glycans only slightly affected CBA susceptibility. 25499264 9 110 theme multiple 1626:1633 arg1 N-glycans 1640:1648 Concomitantly deleting multiple gp41 N-glycans 1603:1648 Concomitantly deleting multiple gp41 N-glycans 1603:1648 Concomitantly deleting multiple gp41 N-glycans was often highly detrimental for viral infectivity. 25499264 4 111 theme glycoprotein 754:765 arg1 incorporation 767:779 envelope glycoprotein incorporation 745:779 envelope glycoprotein incorporation in the viral particle and on the transfected cell 745:829 RESULTS: We generated HIV-1 mutants lacking gp41 N-glycans and determined the influence of these glycan deletions on the viral phenotype (infectivity, CD4 binding, envelope glycoprotein incorporation in the viral particle and on the transfected cell, virus capture by DC-SIGN(+) cells and transmission of DC-SIGN-captured virions to CD4(+) T-lymphocytes) and on the phenotypic susceptibility of HIV-1 to a selection of CBAs. 25499264 4 111 theme glycoprotein 754:765 arg1 infectivity 719:729 infectivity 719:729 infectivity 719:729 RESULTS: We generated HIV-1 mutants lacking gp41 N-glycans and determined the influence of these glycan deletions on the viral phenotype (infectivity, CD4 binding, envelope glycoprotein incorporation in the viral particle and on the transfected cell, virus capture by DC-SIGN(+) cells and transmission of DC-SIGN-captured virions to CD4(+) T-lymphocytes) and on the phenotypic susceptibility of HIV-1 to a selection of CBAs. 25499264 3 112 gly glycoprotein 504:515 arg1 glycoprotein 504:515 the transmembrane envelope glycoprotein gp41 477:520 the transmembrane envelope glycoprotein gp41 477:520 Recently, also an N-glycan on the transmembrane envelope glycoprotein gp41 was shown to be deleted during CBA resistance development. 25499264 2 113 theme N-linked 386:393 arg1 glycans 395:401 multiple N-linked glycans 377:401 multiple N-linked glycans of the surface envelope glycoprotein gp120 377:444 The development of phenotypic resistance to CBAs by the virus is accompanied by the deletion of multiple N-linked glycans of the surface envelope glycoprotein gp120. 25499264 4 114 theme CD4 732:734 arg1 infectivity 719:729 infectivity 719:729 infectivity 719:729 RESULTS: We generated HIV-1 mutants lacking gp41 N-glycans and determined the influence of these glycan deletions on the viral phenotype (infectivity, CD4 binding, envelope glycoprotein incorporation in the viral particle and on the transfected cell, virus capture by DC-SIGN(+) cells and transmission of DC-SIGN-captured virions to CD4(+) T-lymphocytes) and on the phenotypic susceptibility of HIV-1 to a selection of CBAs. 25499264 4 114 theme CD4 732:734 arg1 binding 736:742 CD4 binding 732:742 CD4 binding 732:742 RESULTS: We generated HIV-1 mutants lacking gp41 N-glycans and determined the influence of these glycan deletions on the viral phenotype (infectivity, CD4 binding, envelope glycoprotein incorporation in the viral particle and on the transfected cell, virus capture by DC-SIGN(+) cells and transmission of DC-SIGN-captured virions to CD4(+) T-lymphocytes) and on the phenotypic susceptibility of HIV-1 to a selection of CBAs. 25499264 0 115 theme N-glycans 12:20 arg1 susceptibility 61:74 susceptibility 61:74 susceptibility to the suppressive effects of carbohydrate-binding agents 61:132 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. 25499264 0 115 theme N-glycans 12:20 arg1 role 4:7 The role 0:7 The role of N-glycans of HIV-1 gp41 in virus infectivity 0:55 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. 25499264 13 116 theme N616 2186:2189 arg1 indispensable 2231:2243 indispensable 2231:2243 indispensable 2231:2243 CONCLUSIONS: We revealed the importance of some gp41 N-linked glycans, in particular the N616 glycan which was shown to be absolutely indispensable for the infectivity potential of several virus strains. 25499264 13 116 theme N616 2186:2189 arg1 glycan 2191:2196 the N616 glycan 2182:2196 particular the N616 glycan which was shown to be absolutely indispensable for the infectivity potential of several virus strains 2171:2298 CONCLUSIONS: We revealed the importance of some gp41 N-linked glycans, in particular the N616 glycan which was shown to be absolutely indispensable for the infectivity potential of several virus strains. 25499264 2 117 theme glycoprotein 427:438 arg1 gp120 440:444 the surface envelope glycoprotein gp120 406:444 the surface envelope glycoprotein gp120 406:444 The development of phenotypic resistance to CBAs by the virus is accompanied by the deletion of multiple N-linked glycans of the surface envelope glycoprotein gp120. 25499264 10 118 theme resonance 1724:1732 arg1 technology 1734:1743 surface plasmon resonance technology 1708:1743 surface plasmon resonance technology 1708:1743 Using surface plasmon resonance technology we showed that CBAs have a pronounced affinity for both gp120 and gp41. 25499264 12 119 theme glycan-deletions 2044:2059 arg1 combinations 2010:2021 some combinations 2005:2021 some combinations of two to three gp41 glycan-deletions 2005:2059 Single gp41 glycan deletions had no marked effects on CBA susceptibility, whereas some combinations of two to three gp41 glycan-deletions had a minor effect on CBA activity. 25499264 2 120 theme surface 410:416 arg1 gp120 440:444 the surface envelope glycoprotein gp120 406:444 the surface envelope glycoprotein gp120 406:444 The development of phenotypic resistance to CBAs by the virus is accompanied by the deletion of multiple N-linked glycans of the surface envelope glycoprotein gp120. 25499264 0 121 theme HIV-1 25:29 arg1 N-glycans 12:20 N-glycans 12:20 N-glycans of HIV-1 gp41 12:34 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. 25499264 9 122 theme viral 1683:1687 arg1 infectivity 1689:1699 viral infectivity 1683:1699 viral infectivity 1683:1699 Concomitantly deleting multiple gp41 N-glycans was often highly detrimental for viral infectivity. 25499264 10 123 theme surface 1708:1714 arg1 technology 1734:1743 surface plasmon resonance technology 1708:1743 surface plasmon resonance technology 1708:1743 Using surface plasmon resonance technology we showed that CBAs have a pronounced affinity for both gp120 and gp41. 25499264 4 124 theme HIV-1 976:980 arg1 susceptibility 958:971 the phenotypic susceptibility 943:971 the phenotypic susceptibility of HIV-1 to a selection of CBAs 943:1003 RESULTS: We generated HIV-1 mutants lacking gp41 N-glycans and determined the influence of these glycan deletions on the viral phenotype (infectivity, CD4 binding, envelope glycoprotein incorporation in the viral particle and on the transfected cell, virus capture by DC-SIGN(+) cells and transmission of DC-SIGN-captured virions to CD4(+) T-lymphocytes) and on the phenotypic susceptibility of HIV-1 to a selection of CBAs. 25499264 3 125 theme envelope 495:502 arg1 glycoprotein 504:515 the transmembrane envelope glycoprotein gp41 477:520 the transmembrane envelope glycoprotein gp41 477:520 Recently, also an N-glycan on the transmembrane envelope glycoprotein gp41 was shown to be deleted during CBA resistance development. 25499264 6 126 dep strain 1324:1329 arg1 i.e. 1301:1304 i.e. 1301:1304 i.e. 1301:1304 In particular, lack of an intact N616 glycosylation site was shown to result in the loss of viral infectivity of several (i.e. the X4-tropic IIIB and NL4.3 strains, and the X4/R5-tropic HE strain), but not all (i.e. the R5-tropic ADA strain) studied HIV-1 strains. 25499264 4 127 theme viral 788:792 arg1 particle 794:801 the viral particle 784:801 the viral particle 784:801 RESULTS: We generated HIV-1 mutants lacking gp41 N-glycans and determined the influence of these glycan deletions on the viral phenotype (infectivity, CD4 binding, envelope glycoprotein incorporation in the viral particle and on the transfected cell, virus capture by DC-SIGN(+) cells and transmission of DC-SIGN-captured virions to CD4(+) T-lymphocytes) and on the phenotypic susceptibility of HIV-1 to a selection of CBAs. 25499264 2 128 gly glycoprotein 427:438 arg1 glycoprotein 427:438 the surface envelope glycoprotein gp120 406:444 the surface envelope glycoprotein gp120 406:444 The development of phenotypic resistance to CBAs by the virus is accompanied by the deletion of multiple N-linked glycans of the surface envelope glycoprotein gp120. 25499264 4 129 theme gp41 625:628 arg1 N-glycans 630:638 gp41 N-glycans 625:638 gp41 N-glycans 625:638 RESULTS: We generated HIV-1 mutants lacking gp41 N-glycans and determined the influence of these glycan deletions on the viral phenotype (infectivity, CD4 binding, envelope glycoprotein incorporation in the viral particle and on the transfected cell, virus capture by DC-SIGN(+) cells and transmission of DC-SIGN-captured virions to CD4(+) T-lymphocytes) and on the phenotypic susceptibility of HIV-1 to a selection of CBAs. 25499264 10 130 theme pronounced 1772:1781 arg1 affinity 1783:1790 a pronounced affinity 1770:1790 a pronounced affinity for both gp120 and gp41 1770:1814 Using surface plasmon resonance technology we showed that CBAs have a pronounced affinity for both gp120 and gp41. 25499264 6 131 theme strains 1346:1352 arg1 infectivity 1188:1198 viral infectivity 1182:1198 viral infectivity of several (i.e. the X4-tropic IIIB and NL4.3 strains, and the X4/R5-tropic HE strain), but not all (i.e. the R5-tropic ADA strain) studied HIV-1 strains 1182:1352 In particular, lack of an intact N616 glycosylation site was shown to result in the loss of viral infectivity of several (i.e. the X4-tropic IIIB and NL4.3 strains, and the X4/R5-tropic HE strain), but not all (i.e. the R5-tropic ADA strain) studied HIV-1 strains. 27455909 3 0 theme bp 487:488 arg1 frame 503:507 a 1,029 bp open reading frame 479:507 a 1,029 bp open reading frame encoding 342 amino acid residues 479:540 The cloned full-length SjGnRHR cDNA was 1,468 bp long and contained a 1,029 bp open reading frame encoding 342 amino acid residues, 8 bp of 5' untranslated regions (UTR), and 431 bp of 3' UTR. 27455909 3 1 theme amino 522:526 arg1 residues 533:540 342 amino acid residues 518:540 342 amino acid residues 518:540 The cloned full-length SjGnRHR cDNA was 1,468 bp long and contained a 1,029 bp open reading frame encoding 342 amino acid residues, 8 bp of 5' untranslated regions (UTR), and 431 bp of 3' UTR. 27455909 1 2 theme GnRH 275:278 arg1 receptor 280:287 the GnRH receptor 271:287 the GnRH receptor 271:287 Gonadotropin-releasing hormone (GnRH) plays a vital role in the regulation of reproduction through interaction with a specific receptor (the GnRH receptor). 27455909 1 2 theme GnRH 275:278 arg1 receptor 261:268 a specific receptor 250:268 a specific receptor (the GnRH receptor) 250:288 Gonadotropin-releasing hormone (GnRH) plays a vital role in the regulation of reproduction through interaction with a specific receptor (the GnRH receptor). 27455909 12 3 theme reproduction 1730:1741 arg1 control 1719:1725 the control 1715:1725 the control of reproduction 1715:1741 Results indicate that GnRHR may be involved in diverse S. japonica physiological functions, especially in the control of reproduction. 27455909 7 4 theme three-dimensional 1002:1018 arg1 modeling 1030:1037 three-dimensional structure modeling 1002:1037 three-dimensional structure modeling 1002:1037 Multiple sequence alignment, phylogenetic tree analysis, and three-dimensional structure modeling were conducted to clarify SjGnRHR bioinformatics characteristics. 27455909 10 5 theme SjGnRHR 1365:1371 arg1 quantification 1389:1402 SjGnRHR transcriptional quantification 1365:1402 SjGnRHR transcriptional quantification 1365:1402 SjGnRHR transcriptional quantification confirmed the wide distribution of SjGnRHR in various S. japonica mature tissues. 27455909 6 6 theme acid 854:857 arg1 sequence 859:866 The predicted amino acid sequence 834:866 The predicted amino acid sequence 834:866 The predicted amino acid sequence contained two N-linked glycosylation sites and 18 phosphorylation sites. 27455909 4 7 contain have 642:645 arg2 weight 659:664 a molecular weight 647:664 a molecular weight of 38.75 kDa 647:677 The putative protein was predicted to have a molecular weight of 38.75 kDa and an isoelectric point of 9.47. 27455909 4 7 contain have 642:645 arg1 protein 617:623 The putative protein 604:623 The putative protein 604:623 The putative protein was predicted to have a molecular weight of 38.75 kDa and an isoelectric point of 9.47. 27455909 4 7 contain have 642:645 arg2 point 698:702 an isoelectric point 683:702 an isoelectric point of 9.47 683:710 The putative protein was predicted to have a molecular weight of 38.75 kDa and an isoelectric point of 9.47. 27455909 7 8 theme tree 983:986 arg1 analysis 988:995 phylogenetic tree analysis 970:995 phylogenetic tree analysis 970:995 Multiple sequence alignment, phylogenetic tree analysis, and three-dimensional structure modeling were conducted to clarify SjGnRHR bioinformatics characteristics. 27455909 6 9 link N-linked 882:889 arg1 sites 905:909 two N-linked glycosylation sites 878:909 two N-linked glycosylation sites 878:909 The predicted amino acid sequence contained two N-linked glycosylation sites and 18 phosphorylation sites. 27455909 6 10 theme predicted 838:846 arg1 sequence 859:866 The predicted amino acid sequence 834:866 The predicted amino acid sequence 834:866 The predicted amino acid sequence contained two N-linked glycosylation sites and 18 phosphorylation sites. 27455909 7 11 theme sequence 950:957 arg1 alignment 959:967 Multiple sequence alignment 941:967 Multiple sequence alignment 941:967 Multiple sequence alignment, phylogenetic tree analysis, and three-dimensional structure modeling were conducted to clarify SjGnRHR bioinformatics characteristics. 27455909 1 12 theme Gonadotropin-releasing 134:155 arg1 hormone 157:163 Gonadotropin-releasing hormone 134:163 Gonadotropin-releasing hormone (GnRH) 134:170 Gonadotropin-releasing hormone (GnRH) plays a vital role in the regulation of reproduction through interaction with a specific receptor (the GnRH receptor). 27455909 1 12 theme Gonadotropin-releasing 134:155 arg1 GnRH 166:169 GnRH 166:169 GnRH 166:169 Gonadotropin-releasing hormone (GnRH) plays a vital role in the regulation of reproduction through interaction with a specific receptor (the GnRH receptor). 27455909 5 13 theme protein-coupled 801:815 arg1 family 826:831 the rhodopsin-type (class A) G protein-coupled receptor family 770:831 the rhodopsin-type (class A) G protein-coupled receptor family 770:831 In addition, this protein was identified as belonging to the rhodopsin-type (class A) G protein-coupled receptor family. 27455909 0 14 theme Receptor 76:83 arg1 Identification 0:13 Identification 0:13 Identification 0:13 Identification and Expression Profile of the Gonadotropin-Releasing Hormone Receptor in Common Chinese Cuttlefish, Sepiella japonica. 27455909 0 14 theme Receptor 76:83 arg1 Profile 30:36 Expression Profile 19:36 Expression Profile 19:36 Identification and Expression Profile of the Gonadotropin-Releasing Hormone Receptor in Common Chinese Cuttlefish, Sepiella japonica. 27455909 3 15 theme regions 567:573 arg1 frame 503:507 a 1,029 bp open reading frame 479:507 a 1,029 bp open reading frame encoding 342 amino acid residues 479:540 The cloned full-length SjGnRHR cDNA was 1,468 bp long and contained a 1,029 bp open reading frame encoding 342 amino acid residues, 8 bp of 5' untranslated regions (UTR), and 431 bp of 3' UTR. 27455909 3 15 theme regions 567:573 arg1 bp 545:546 8 bp 543:546 8 bp of 5' untranslated regions (UTR) 543:579 The cloned full-length SjGnRHR cDNA was 1,468 bp long and contained a 1,029 bp open reading frame encoding 342 amino acid residues, 8 bp of 5' untranslated regions (UTR), and 431 bp of 3' UTR. 27455909 3 15 theme regions 567:573 arg1 bp 590:591 431 bp 586:591 431 bp of 3' UTR 586:601 The cloned full-length SjGnRHR cDNA was 1,468 bp long and contained a 1,029 bp open reading frame encoding 342 amino acid residues, 8 bp of 5' untranslated regions (UTR), and 431 bp of 3' UTR. 27455909 5 16 theme rhodopsin-type 774:787 arg1 family 826:831 the rhodopsin-type (class A) G protein-coupled receptor family 770:831 the rhodopsin-type (class A) G protein-coupled receptor family 770:831 In addition, this protein was identified as belonging to the rhodopsin-type (class A) G protein-coupled receptor family. 27455909 4 17 theme putative 608:615 arg1 protein 617:623 The putative protein 604:623 The putative protein 604:623 The putative protein was predicted to have a molecular weight of 38.75 kDa and an isoelectric point of 9.47. 27455909 0 18 theme Common 88:93 arg1 Sepiella 115:122 Sepiella 115:122 Sepiella 115:122 Identification and Expression Profile of the Gonadotropin-Releasing Hormone Receptor in Common Chinese Cuttlefish, Sepiella japonica. 27455909 0 18 theme Common 88:93 arg1 Cuttlefish 103:112 Common Chinese Cuttlefish 88:112 Common Chinese Cuttlefish 88:112 Identification and Expression Profile of the Gonadotropin-Releasing Hormone Receptor in Common Chinese Cuttlefish, Sepiella japonica. 27455909 5 19 theme class 790:794 arg1 A 796:796 class A 790:796 class A 790:796 In addition, this protein was identified as belonging to the rhodopsin-type (class A) G protein-coupled receptor family. 27455909 12 20 theme diverse 1656:1662 arg1 functions 1690:1698 diverse S. japonica physiological functions 1656:1698 diverse S. japonica physiological functions 1656:1698 Results indicate that GnRHR may be involved in diverse S. japonica physiological functions, especially in the control of reproduction. 27455909 6 21 theme N-linked 882:889 arg1 sites 905:909 two N-linked glycosylation sites 878:909 two N-linked glycosylation sites 878:909 The predicted amino acid sequence contained two N-linked glycosylation sites and 18 phosphorylation sites. 27455909 0 22 from Identification 0:13 arg1 Sepiella 115:122 Sepiella 115:122 Sepiella 115:122 Identification and Expression Profile of the Gonadotropin-Releasing Hormone Receptor in Common Chinese Cuttlefish, Sepiella japonica. 27455909 0 22 from Identification 0:13 arg1 Cuttlefish 103:112 Common Chinese Cuttlefish 88:112 Common Chinese Cuttlefish 88:112 Identification and Expression Profile of the Gonadotropin-Releasing Hormone Receptor in Common Chinese Cuttlefish, Sepiella japonica. 27455909 4 23 theme molecular 649:657 arg1 weight 659:664 a molecular weight 647:664 a molecular weight of 38.75 kDa 647:677 The putative protein was predicted to have a molecular weight of 38.75 kDa and an isoelectric point of 9.47. 27455909 0 24 dep Sepiella 115:122 arg1 japonica 124:131 Sepiella japonica 115:131 Sepiella japonica 115:131 Identification and Expression Profile of the Gonadotropin-Releasing Hormone Receptor in Common Chinese Cuttlefish, Sepiella japonica. 27455909 10 25 theme SjGnRHR 1439:1445 arg1 distribution 1423:1434 the wide distribution 1414:1434 the wide distribution of SjGnRHR in various S. japonica mature tissues 1414:1483 SjGnRHR transcriptional quantification confirmed the wide distribution of SjGnRHR in various S. japonica mature tissues. 27455909 3 26 theme full-length 422:432 arg1 long 460:463 long 460:463 long 460:463 The cloned full-length SjGnRHR cDNA was 1,468 bp long and contained a 1,029 bp open reading frame encoding 342 amino acid residues, 8 bp of 5' untranslated regions (UTR), and 431 bp of 3' UTR. 27455909 3 26 theme full-length 422:432 arg1 cDNA 442:445 The cloned full-length SjGnRHR cDNA 411:445 The cloned full-length SjGnRHR cDNA 411:445 The cloned full-length SjGnRHR cDNA was 1,468 bp long and contained a 1,029 bp open reading frame encoding 342 amino acid residues, 8 bp of 5' untranslated regions (UTR), and 431 bp of 3' UTR. 27455909 10 27 dep S. 1458:1459 arg1 japonica 1461:1468 japonica 1461:1468 japonica 1461:1468 SjGnRHR transcriptional quantification confirmed the wide distribution of SjGnRHR in various S. japonica mature tissues. 27455909 3 28 contain contained 469:477 arg2 frame 503:507 a 1,029 bp open reading frame 479:507 a 1,029 bp open reading frame encoding 342 amino acid residues 479:540 The cloned full-length SjGnRHR cDNA was 1,468 bp long and contained a 1,029 bp open reading frame encoding 342 amino acid residues, 8 bp of 5' untranslated regions (UTR), and 431 bp of 3' UTR. 27455909 3 28 contain contained 469:477 arg1 long 460:463 long 460:463 long 460:463 The cloned full-length SjGnRHR cDNA was 1,468 bp long and contained a 1,029 bp open reading frame encoding 342 amino acid residues, 8 bp of 5' untranslated regions (UTR), and 431 bp of 3' UTR. 27455909 3 28 contain contained 469:477 arg2 bp 590:591 431 bp 586:591 431 bp of 3' UTR 586:601 The cloned full-length SjGnRHR cDNA was 1,468 bp long and contained a 1,029 bp open reading frame encoding 342 amino acid residues, 8 bp of 5' untranslated regions (UTR), and 431 bp of 3' UTR. 27455909 3 28 contain contained 469:477 arg1 cDNA 442:445 The cloned full-length SjGnRHR cDNA 411:445 The cloned full-length SjGnRHR cDNA 411:445 The cloned full-length SjGnRHR cDNA was 1,468 bp long and contained a 1,029 bp open reading frame encoding 342 amino acid residues, 8 bp of 5' untranslated regions (UTR), and 431 bp of 3' UTR. 27455909 3 28 contain contained 469:477 arg2 bp 545:546 8 bp 543:546 8 bp of 5' untranslated regions (UTR) 543:579 The cloned full-length SjGnRHR cDNA was 1,468 bp long and contained a 1,029 bp open reading frame encoding 342 amino acid residues, 8 bp of 5' untranslated regions (UTR), and 431 bp of 3' UTR. 27455909 6 29 contain contained 868:876 arg2 sites 934:938 18 phosphorylation sites 915:938 18 phosphorylation sites 915:938 The predicted amino acid sequence contained two N-linked glycosylation sites and 18 phosphorylation sites. 27455909 6 29 contain contained 868:876 arg2 sites 905:909 two N-linked glycosylation sites 878:909 two N-linked glycosylation sites 878:909 The predicted amino acid sequence contained two N-linked glycosylation sites and 18 phosphorylation sites. 27455909 6 29 contain contained 868:876 arg1 sequence 859:866 The predicted amino acid sequence 834:866 The predicted amino acid sequence 834:866 The predicted amino acid sequence contained two N-linked glycosylation sites and 18 phosphorylation sites. 27455909 0 30 theme Expression 19:28 arg1 Profile 30:36 Expression Profile 19:36 Expression Profile 19:36 Identification and Expression Profile of the Gonadotropin-Releasing Hormone Receptor in Common Chinese Cuttlefish, Sepiella japonica. 27455909 9 31 theme S. 1278:1279 arg1 receptor 1295:1302 the S. japonica GnRH receptor 1274:1302 the S. japonica GnRH receptor 1274:1302 The interaction between the S. japonica GnRH receptor and its ligand was clarified using internalization analysis. 27455909 10 32 theme various 1450:1456 arg1 tissues 1477:1483 various S. japonica mature tissues 1450:1483 various S. japonica mature tissues 1450:1483 SjGnRHR transcriptional quantification confirmed the wide distribution of SjGnRHR in various S. japonica mature tissues. 27455909 7 33 theme bioinformatics 1073:1086 arg1 characteristics 1088:1102 SjGnRHR bioinformatics characteristics 1065:1102 SjGnRHR bioinformatics characteristics 1065:1102 Multiple sequence alignment, phylogenetic tree analysis, and three-dimensional structure modeling were conducted to clarify SjGnRHR bioinformatics characteristics. 27455909 9 34 theme GnRH 1290:1293 arg1 receptor 1295:1302 the S. japonica GnRH receptor 1274:1302 the S. japonica GnRH receptor 1274:1302 The interaction between the S. japonica GnRH receptor and its ligand was clarified using internalization analysis. 27455909 6 35 gly glycosylation 891:903 arg2 sites 905:909 two N-linked glycosylation sites 878:909 two N-linked glycosylation sites 878:909 The predicted amino acid sequence contained two N-linked glycosylation sites and 18 phosphorylation sites. 27455909 6 35 gly glycosylation 891:903 arg2 two 878:880 two 878:880 two 878:880 The predicted amino acid sequence contained two N-linked glycosylation sites and 18 phosphorylation sites. 27455909 0 36 theme Gonadotropin-Releasing 45:66 arg1 Receptor 76:83 the Gonadotropin-Releasing Hormone Receptor 41:83 the Gonadotropin-Releasing Hormone Receptor 41:83 Identification and Expression Profile of the Gonadotropin-Releasing Hormone Receptor in Common Chinese Cuttlefish, Sepiella japonica. 27455909 0 37 from Profile 30:36 arg1 Sepiella 115:122 Sepiella 115:122 Sepiella 115:122 Identification and Expression Profile of the Gonadotropin-Releasing Hormone Receptor in Common Chinese Cuttlefish, Sepiella japonica. 27455909 0 37 from Profile 30:36 arg1 Cuttlefish 103:112 Common Chinese Cuttlefish 88:112 Common Chinese Cuttlefish 88:112 Identification and Expression Profile of the Gonadotropin-Releasing Hormone Receptor in Common Chinese Cuttlefish, Sepiella japonica. 27455909 11 38 theme SjGnRHR 1530:1536 arg1 profile 1519:1525 the transcriptional profile 1499:1525 the transcriptional profile of SjGnRHR in the female brain and ovary during gonadal development 1499:1593 In addition, the transcriptional profile of SjGnRHR in the female brain and ovary during gonadal development was analyzed. 27455909 4 39 theme isoelectric 686:696 arg1 point 698:702 an isoelectric point 683:702 an isoelectric point of 9.47 683:710 The putative protein was predicted to have a molecular weight of 38.75 kDa and an isoelectric point of 9.47. 27455909 11 40 theme female 1545:1550 arg1 brain 1552:1556 brain 1552:1556 brain 1552:1556 In addition, the transcriptional profile of SjGnRHR in the female brain and ovary during gonadal development was analyzed. 27455909 2 41 theme receptor 315:322 arg1 gene 324:327 the GnRH receptor gene 306:327 the GnRH receptor gene from the cuttlefish Sepiella japonica (SjGnRHR) 306:375 In this study, the GnRH receptor gene from the cuttlefish Sepiella japonica (SjGnRHR) was identified and characterized. 27455909 3 42 theme open 490:493 arg1 frame 503:507 a 1,029 bp open reading frame 479:507 a 1,029 bp open reading frame encoding 342 amino acid residues 479:540 The cloned full-length SjGnRHR cDNA was 1,468 bp long and contained a 1,029 bp open reading frame encoding 342 amino acid residues, 8 bp of 5' untranslated regions (UTR), and 431 bp of 3' UTR. 27455909 1 43 with interaction 233:243 arg1 receptor 280:287 the GnRH receptor 271:287 the GnRH receptor 271:287 Gonadotropin-releasing hormone (GnRH) plays a vital role in the regulation of reproduction through interaction with a specific receptor (the GnRH receptor). 27455909 1 43 with interaction 233:243 arg1 receptor 261:268 a specific receptor 250:268 a specific receptor (the GnRH receptor) 250:288 Gonadotropin-releasing hormone (GnRH) plays a vital role in the regulation of reproduction through interaction with a specific receptor (the GnRH receptor). 27455909 2 44 theme cuttlefish 338:347 arg1 SjGnRHR 368:374 SjGnRHR 368:374 SjGnRHR 368:374 In this study, the GnRH receptor gene from the cuttlefish Sepiella japonica (SjGnRHR) was identified and characterized. 27455909 2 44 theme cuttlefish 338:347 arg1 japonica 358:365 the cuttlefish Sepiella japonica 334:365 the cuttlefish Sepiella japonica (SjGnRHR) 334:375 In this study, the GnRH receptor gene from the cuttlefish Sepiella japonica (SjGnRHR) was identified and characterized. 27455909 9 45 theme internalization 1339:1353 arg1 analysis 1355:1362 internalization analysis 1339:1362 internalization analysis 1339:1362 The interaction between the S. japonica GnRH receptor and its ligand was clarified using internalization analysis. 27455909 7 46 theme structure 1020:1028 arg1 modeling 1030:1037 three-dimensional structure modeling 1002:1037 three-dimensional structure modeling 1002:1037 Multiple sequence alignment, phylogenetic tree analysis, and three-dimensional structure modeling were conducted to clarify SjGnRHR bioinformatics characteristics. 27455909 11 47 theme transcriptional 1503:1517 arg1 profile 1519:1525 the transcriptional profile 1499:1525 the transcriptional profile of SjGnRHR in the female brain and ovary during gonadal development 1499:1593 In addition, the transcriptional profile of SjGnRHR in the female brain and ovary during gonadal development was analyzed. 27455909 1 48 theme vital 180:184 arg1 role 186:189 a vital role 178:189 a vital role 178:189 Gonadotropin-releasing hormone (GnRH) plays a vital role in the regulation of reproduction through interaction with a specific receptor (the GnRH receptor). 27455909 8 49 theme In 1105:1106 arg1 expression 1122:1131 In vitro SjGnRHR expression 1105:1131 In vitro SjGnRHR expression 1105:1131 In vitro SjGnRHR expression was carried out using HEK293 cells and the pEGFP-N1 plasmid, to verify the transmembrane properties of this protein. 27455909 11 50 dep brain 1552:1556 arg1 the 1541:1543 the 1541:1543 the 1541:1543 In addition, the transcriptional profile of SjGnRHR in the female brain and ovary during gonadal development was analyzed. 27455909 8 51 theme SjGnRHR 1114:1120 arg1 expression 1122:1131 In vitro SjGnRHR expression 1105:1131 In vitro SjGnRHR expression 1105:1131 In vitro SjGnRHR expression was carried out using HEK293 cells and the pEGFP-N1 plasmid, to verify the transmembrane properties of this protein. 27455909 2 52 from japonica 358:365 arg1 gene 324:327 the GnRH receptor gene 306:327 the GnRH receptor gene from the cuttlefish Sepiella japonica (SjGnRHR) 306:375 In this study, the GnRH receptor gene from the cuttlefish Sepiella japonica (SjGnRHR) was identified and characterized. 27455909 8 53 theme pEGFP-N1 1176:1183 arg1 plasmid 1185:1191 the pEGFP-N1 plasmid 1172:1191 the pEGFP-N1 plasmid 1172:1191 In vitro SjGnRHR expression was carried out using HEK293 cells and the pEGFP-N1 plasmid, to verify the transmembrane properties of this protein. 27455909 7 54 theme phylogenetic 970:981 arg1 analysis 988:995 phylogenetic tree analysis 970:995 phylogenetic tree analysis 970:995 Multiple sequence alignment, phylogenetic tree analysis, and three-dimensional structure modeling were conducted to clarify SjGnRHR bioinformatics characteristics. 27455909 12 55 dep S. 1664:1665 arg1 japonica 1667:1674 japonica 1667:1674 japonica 1667:1674 Results indicate that GnRHR may be involved in diverse S. japonica physiological functions, especially in the control of reproduction. 27455909 3 56 theme acid 528:531 arg1 residues 533:540 342 amino acid residues 518:540 342 amino acid residues 518:540 The cloned full-length SjGnRHR cDNA was 1,468 bp long and contained a 1,029 bp open reading frame encoding 342 amino acid residues, 8 bp of 5' untranslated regions (UTR), and 431 bp of 3' UTR. 27455909 6 57 theme amino 848:852 arg1 sequence 859:866 The predicted amino acid sequence 834:866 The predicted amino acid sequence 834:866 The predicted amino acid sequence contained two N-linked glycosylation sites and 18 phosphorylation sites. 27455909 3 58 theme 1,029 481:485 arg1 bp 487:488 bp 487:488 bp 487:488 The cloned full-length SjGnRHR cDNA was 1,468 bp long and contained a 1,029 bp open reading frame encoding 342 amino acid residues, 8 bp of 5' untranslated regions (UTR), and 431 bp of 3' UTR. 27455909 1 59 theme reproduction 212:223 arg1 regulation 198:207 the regulation 194:207 the regulation of reproduction through interaction with a specific receptor (the GnRH receptor) 194:288 Gonadotropin-releasing hormone (GnRH) plays a vital role in the regulation of reproduction through interaction with a specific receptor (the GnRH receptor). 27455909 10 60 from distribution 1423:1434 arg1 tissues 1477:1483 various S. japonica mature tissues 1450:1483 various S. japonica mature tissues 1450:1483 SjGnRHR transcriptional quantification confirmed the wide distribution of SjGnRHR in various S. japonica mature tissues. 27455909 7 61 theme Multiple 941:948 arg1 alignment 959:967 Multiple sequence alignment 941:967 Multiple sequence alignment 941:967 Multiple sequence alignment, phylogenetic tree analysis, and three-dimensional structure modeling were conducted to clarify SjGnRHR bioinformatics characteristics. 27455909 11 62 from profile 1519:1525 arg1 brain 1552:1556 brain 1552:1556 brain 1552:1556 In addition, the transcriptional profile of SjGnRHR in the female brain and ovary during gonadal development was analyzed. 27455909 11 62 from profile 1519:1525 arg1 ovary 1562:1566 ovary 1562:1566 ovary 1562:1566 In addition, the transcriptional profile of SjGnRHR in the female brain and ovary during gonadal development was analyzed. 27455909 8 63 theme HEK293 1155:1160 arg1 cells 1162:1166 HEK293 cells 1155:1166 HEK293 cells 1155:1166 In vitro SjGnRHR expression was carried out using HEK293 cells and the pEGFP-N1 plasmid, to verify the transmembrane properties of this protein. 27455909 8 64 theme transmembrane 1208:1220 arg1 properties 1222:1231 the transmembrane properties 1204:1231 the transmembrane properties of this protein 1204:1247 In vitro SjGnRHR expression was carried out using HEK293 cells and the pEGFP-N1 plasmid, to verify the transmembrane properties of this protein. 27455909 12 65 theme S. 1664:1665 arg1 functions 1690:1698 diverse S. japonica physiological functions 1656:1698 diverse S. japonica physiological functions 1656:1698 Results indicate that GnRHR may be involved in diverse S. japonica physiological functions, especially in the control of reproduction. 27455909 6 66 theme phosphorylation 918:932 arg1 sites 934:938 18 phosphorylation sites 915:938 18 phosphorylation sites 915:938 The predicted amino acid sequence contained two N-linked glycosylation sites and 18 phosphorylation sites. 27455909 3 67 theme untranslated 554:565 arg1 regions 567:573 5' untranslated regions 551:573 5' untranslated regions (UTR) 551:579 The cloned full-length SjGnRHR cDNA was 1,468 bp long and contained a 1,029 bp open reading frame encoding 342 amino acid residues, 8 bp of 5' untranslated regions (UTR), and 431 bp of 3' UTR. 27455909 3 67 theme untranslated 554:565 arg1 UTR 576:578 UTR 576:578 UTR 576:578 The cloned full-length SjGnRHR cDNA was 1,468 bp long and contained a 1,029 bp open reading frame encoding 342 amino acid residues, 8 bp of 5' untranslated regions (UTR), and 431 bp of 3' UTR. 27455909 12 68 theme physiological 1676:1688 arg1 functions 1690:1698 diverse S. japonica physiological functions 1656:1698 diverse S. japonica physiological functions 1656:1698 Results indicate that GnRHR may be involved in diverse S. japonica physiological functions, especially in the control of reproduction. 27455909 9 69 dep S. 1278:1279 arg1 japonica 1281:1288 japonica 1281:1288 japonica 1281:1288 The interaction between the S. japonica GnRH receptor and its ligand was clarified using internalization analysis. 27455909 8 70 theme protein 1241:1247 arg1 properties 1222:1231 the transmembrane properties 1204:1231 the transmembrane properties of this protein 1204:1247 In vitro SjGnRHR expression was carried out using HEK293 cells and the pEGFP-N1 plasmid, to verify the transmembrane properties of this protein. 27455909 0 71 theme Chinese 95:101 arg1 Sepiella 115:122 Sepiella 115:122 Sepiella 115:122 Identification and Expression Profile of the Gonadotropin-Releasing Hormone Receptor in Common Chinese Cuttlefish, Sepiella japonica. 27455909 0 71 theme Chinese 95:101 arg1 Cuttlefish 103:112 Common Chinese Cuttlefish 88:112 Common Chinese Cuttlefish 88:112 Identification and Expression Profile of the Gonadotropin-Releasing Hormone Receptor in Common Chinese Cuttlefish, Sepiella japonica. 27455909 6 72 theme glycosylation 891:903 arg1 sites 905:909 two N-linked glycosylation sites 878:909 two N-linked glycosylation sites 878:909 The predicted amino acid sequence contained two N-linked glycosylation sites and 18 phosphorylation sites. 27455909 8 73 dep In 1105:1106 arg1 vitro 1108:1112 vitro 1108:1112 vitro 1108:1112 In vitro SjGnRHR expression was carried out using HEK293 cells and the pEGFP-N1 plasmid, to verify the transmembrane properties of this protein. 27455909 10 74 theme transcriptional 1373:1387 arg1 quantification 1389:1402 SjGnRHR transcriptional quantification 1365:1402 SjGnRHR transcriptional quantification 1365:1402 SjGnRHR transcriptional quantification confirmed the wide distribution of SjGnRHR in various S. japonica mature tissues. 27455909 4 75 theme kDa 675:677 arg1 point 698:702 an isoelectric point 683:702 an isoelectric point of 9.47 683:710 The putative protein was predicted to have a molecular weight of 38.75 kDa and an isoelectric point of 9.47. 27455909 4 75 theme kDa 675:677 arg1 weight 659:664 a molecular weight 647:664 a molecular weight of 38.75 kDa 647:677 The putative protein was predicted to have a molecular weight of 38.75 kDa and an isoelectric point of 9.47. 27455909 3 76 theme SjGnRHR 434:440 arg1 long 460:463 long 460:463 long 460:463 The cloned full-length SjGnRHR cDNA was 1,468 bp long and contained a 1,029 bp open reading frame encoding 342 amino acid residues, 8 bp of 5' untranslated regions (UTR), and 431 bp of 3' UTR. 27455909 3 76 theme SjGnRHR 434:440 arg1 cDNA 442:445 The cloned full-length SjGnRHR cDNA 411:445 The cloned full-length SjGnRHR cDNA 411:445 The cloned full-length SjGnRHR cDNA was 1,468 bp long and contained a 1,029 bp open reading frame encoding 342 amino acid residues, 8 bp of 5' untranslated regions (UTR), and 431 bp of 3' UTR. 27455909 5 77 theme receptor 817:824 arg1 family 826:831 the rhodopsin-type (class A) G protein-coupled receptor family 770:831 the rhodopsin-type (class A) G protein-coupled receptor family 770:831 In addition, this protein was identified as belonging to the rhodopsin-type (class A) G protein-coupled receptor family. 27455909 10 78 theme wide 1418:1421 arg1 distribution 1423:1434 the wide distribution 1414:1434 the wide distribution of SjGnRHR in various S. japonica mature tissues 1414:1483 SjGnRHR transcriptional quantification confirmed the wide distribution of SjGnRHR in various S. japonica mature tissues. 27455909 3 79 theme cloned 415:420 arg1 long 460:463 long 460:463 long 460:463 The cloned full-length SjGnRHR cDNA was 1,468 bp long and contained a 1,029 bp open reading frame encoding 342 amino acid residues, 8 bp of 5' untranslated regions (UTR), and 431 bp of 3' UTR. 27455909 3 79 theme cloned 415:420 arg1 cDNA 442:445 The cloned full-length SjGnRHR cDNA 411:445 The cloned full-length SjGnRHR cDNA 411:445 The cloned full-length SjGnRHR cDNA was 1,468 bp long and contained a 1,029 bp open reading frame encoding 342 amino acid residues, 8 bp of 5' untranslated regions (UTR), and 431 bp of 3' UTR. 27455909 10 80 theme S. 1458:1459 arg1 tissues 1477:1483 various S. japonica mature tissues 1450:1483 various S. japonica mature tissues 1450:1483 SjGnRHR transcriptional quantification confirmed the wide distribution of SjGnRHR in various S. japonica mature tissues. 27455909 5 81 dep rhodopsin-type 774:787 arg1 A 796:796 class A 790:796 class A 790:796 In addition, this protein was identified as belonging to the rhodopsin-type (class A) G protein-coupled receptor family. 27455909 7 82 theme SjGnRHR 1065:1071 arg1 characteristics 1088:1102 SjGnRHR bioinformatics characteristics 1065:1102 SjGnRHR bioinformatics characteristics 1065:1102 Multiple sequence alignment, phylogenetic tree analysis, and three-dimensional structure modeling were conducted to clarify SjGnRHR bioinformatics characteristics. 27455909 4 83 theme 9.47 707:710 arg1 point 698:702 an isoelectric point 683:702 an isoelectric point of 9.47 683:710 The putative protein was predicted to have a molecular weight of 38.75 kDa and an isoelectric point of 9.47. 27455909 4 83 theme 9.47 707:710 arg1 weight 659:664 a molecular weight 647:664 a molecular weight of 38.75 kDa 647:677 The putative protein was predicted to have a molecular weight of 38.75 kDa and an isoelectric point of 9.47. 27455909 0 84 theme Hormone 68:74 arg1 Receptor 76:83 the Gonadotropin-Releasing Hormone Receptor 41:83 the Gonadotropin-Releasing Hormone Receptor 41:83 Identification and Expression Profile of the Gonadotropin-Releasing Hormone Receptor in Common Chinese Cuttlefish, Sepiella japonica. 27455909 10 85 theme mature 1470:1475 arg1 tissues 1477:1483 various S. japonica mature tissues 1450:1483 various S. japonica mature tissues 1450:1483 SjGnRHR transcriptional quantification confirmed the wide distribution of SjGnRHR in various S. japonica mature tissues. 27455909 11 86 theme gonadal 1575:1581 arg1 development 1583:1593 gonadal development 1575:1593 gonadal development 1575:1593 In addition, the transcriptional profile of SjGnRHR in the female brain and ovary during gonadal development was analyzed. 27455909 2 87 theme GnRH 310:313 arg1 gene 324:327 the GnRH receptor gene 306:327 the GnRH receptor gene from the cuttlefish Sepiella japonica (SjGnRHR) 306:375 In this study, the GnRH receptor gene from the cuttlefish Sepiella japonica (SjGnRHR) was identified and characterized. 27455909 3 88 theme reading 495:501 arg1 frame 503:507 a 1,029 bp open reading frame 479:507 a 1,029 bp open reading frame encoding 342 amino acid residues 479:540 The cloned full-length SjGnRHR cDNA was 1,468 bp long and contained a 1,029 bp open reading frame encoding 342 amino acid residues, 8 bp of 5' untranslated regions (UTR), and 431 bp of 3' UTR. 27455909 2 89 theme Sepiella 349:356 arg1 SjGnRHR 368:374 SjGnRHR 368:374 SjGnRHR 368:374 In this study, the GnRH receptor gene from the cuttlefish Sepiella japonica (SjGnRHR) was identified and characterized. 27455909 2 89 theme Sepiella 349:356 arg1 japonica 358:365 the cuttlefish Sepiella japonica 334:365 the cuttlefish Sepiella japonica (SjGnRHR) 334:375 In this study, the GnRH receptor gene from the cuttlefish Sepiella japonica (SjGnRHR) was identified and characterized. 27455909 1 90 theme specific 252:259 arg1 receptor 280:287 the GnRH receptor 271:287 the GnRH receptor 271:287 Gonadotropin-releasing hormone (GnRH) plays a vital role in the regulation of reproduction through interaction with a specific receptor (the GnRH receptor). 27455909 1 90 theme specific 252:259 arg1 receptor 261:268 a specific receptor 250:268 a specific receptor (the GnRH receptor) 250:288 Gonadotropin-releasing hormone (GnRH) plays a vital role in the regulation of reproduction through interaction with a specific receptor (the GnRH receptor). 25137014 10 0 dep https 2019:2023 arg1 //desairegroup.ku.edu/research 2025:2054 //desairegroup.ku.edu/research 2025:2054 https://desairegroup.ku.edu/research 2019:2054 The software is provided at https://desairegroup.ku.edu/research. 25137014 0 1 theme data 149:152 arg1 sets 154:157 small data sets 143:157 small data sets 143:157 New glycoproteomics software, GlycoPep Evaluator, generates decoy glycopeptides de novo and enables accurate false discovery rate analysis for small data sets. 25137014 3 2 dep way 664:666 arg1 provide 717:723 provide 717:723 provide the false discovery rate (FDR) 717:754 While several emerging automated tools are developed, no consensus is present in the field about the best way to determine the reliability of the tools and/or provide the false discovery rate (FDR). 25137014 3 2 dep way 664:666 arg1 determine 671:679 determine 671:679 determine the reliability of the tools 671:708 While several emerging automated tools are developed, no consensus is present in the field about the best way to determine the reliability of the tools and/or provide the false discovery rate (FDR). 25137014 3 3 from field 643:647 arg1 present 628:634 present 628:634 present 628:634 While several emerging automated tools are developed, no consensus is present in the field about the best way to determine the reliability of the tools and/or provide the false discovery rate (FDR). 25137014 8 4 theme ratio 1802:1806 arg1 number 1770:1775 the number 1766:1775 the number of decoy matches and the ratio of the number of targets to decoys, for small data sets 1766:1862 The decoys, along with target glycopeptides, are scored against the ETD data, from which FDRs can be calculated accurately based on the number of decoy matches and the ratio of the number of targets to decoys, for small data sets. 25137014 2 5 theme protein 302:308 arg1 information 324:334 site-specific protein glycosylation information 288:334 site-specific protein glycosylation information 288:334 In order to obtain site-specific protein glycosylation information, intact glycopeptides, with the glycan attached to the peptide sequence, are characterized by tandem mass spectrometry (MS/MS) methods such as collision-induced dissociation (CID) and electron transfer dissociation (ETD). 25137014 6 6 theme decoy 1512:1516 arg1 database 1518:1525 a decoy database 1510:1525 a decoy database 1510:1525 To address the need to accurately determine FDRs for automated glycopeptide assignments, we developed GlycoPep Evaluator (GPE), a tool that helps to measure FDRs in identifying glycopeptides without using a decoy database. 25137014 5 7 theme consensus 1179:1187 arg1 sequence 1189:1196 a consensus sequence 1177:1196 a consensus sequence 1177:1196 Nonetheless, this approach is not optimal in measuring the confidence of N-linked glycopeptide matches, because the glycopeptide data set is considerably smaller compared to that of peptides, and the requirement of a consensus sequence for N-glycosylation further limits the number of possible decoy glycopeptides tested in a database search. 25137014 3 8 theme tools 704:708 arg1 reliability 685:695 the reliability 681:695 the reliability of the tools 681:708 While several emerging automated tools are developed, no consensus is present in the field about the best way to determine the reliability of the tools and/or provide the false discovery rate (FDR). 25137014 8 9 theme small 1848:1852 arg1 sets 1859:1862 small data sets 1848:1862 small data sets 1848:1862 The decoys, along with target glycopeptides, are scored against the ETD data, from which FDRs can be calculated accurately based on the number of decoy matches and the ratio of the number of targets to decoys, for small data sets. 25137014 2 10 theme intact 337:342 arg1 glycopeptides 344:356 intact glycopeptides 337:356 intact glycopeptides 337:356 In order to obtain site-specific protein glycosylation information, intact glycopeptides, with the glycan attached to the peptide sequence, are characterized by tandem mass spectrometry (MS/MS) methods such as collision-induced dissociation (CID) and electron transfer dissociation (ETD). 25137014 1 11 theme significant 191:201 arg1 molecules 209:217 biologically significant large molecules 178:217 biologically significant large molecules that participate in numerous cellular activities 178:266 Glycoproteins are biologically significant large molecules that participate in numerous cellular activities. 25137014 1 11 theme significant 191:201 arg1 Glycoproteins 160:172 Glycoproteins 160:172 Glycoproteins 160:172 Glycoproteins are biologically significant large molecules that participate in numerous cellular activities. 25137014 7 12 theme 1:20 1606:1609 arg1 ratio 1627:1631 a 1:20 target-to-decoy ratio 1604:1631 a 1:20 target-to-decoy ratio 1604:1631 GPE generates decoy glycopeptides de novo for every target glycopeptide, in a 1:20 target-to-decoy ratio. 25137014 3 13 theme false 729:733 arg1 rate 745:748 the false discovery rate 725:748 the false discovery rate (FDR) 725:754 While several emerging automated tools are developed, no consensus is present in the field about the best way to determine the reliability of the tools and/or provide the false discovery rate (FDR). 25137014 3 13 theme false 729:733 arg1 FDR 751:753 FDR 751:753 FDR 751:753 While several emerging automated tools are developed, no consensus is present in the field about the best way to determine the reliability of the tools and/or provide the false discovery rate (FDR). 25137014 0 14 theme discovery 115:123 arg1 rate 125:128 false discovery rate 109:128 accurate false discovery rate analysis for small data sets 100:157 New glycoproteomics software, GlycoPep Evaluator, generates decoy glycopeptides de novo and enables accurate false discovery rate analysis for small data sets. 25137014 5 15 theme N-linked 1035:1042 arg1 matches 1057:1063 N-linked glycopeptide matches 1035:1063 N-linked glycopeptide matches 1035:1063 Nonetheless, this approach is not optimal in measuring the confidence of N-linked glycopeptide matches, because the glycopeptide data set is considerably smaller compared to that of peptides, and the requirement of a consensus sequence for N-glycosylation further limits the number of possible decoy glycopeptides tested in a database search. 25137014 3 16 theme emerging 572:579 arg1 tools 591:595 several emerging automated tools 564:595 several emerging automated tools 564:595 While several emerging automated tools are developed, no consensus is present in the field about the best way to determine the reliability of the tools and/or provide the false discovery rate (FDR). 25137014 8 17 theme ETD 1702:1704 arg1 data 1706:1709 the ETD data 1698:1709 the ETD data 1698:1709 The decoys, along with target glycopeptides, are scored against the ETD data, from which FDRs can be calculated accurately based on the number of decoy matches and the ratio of the number of targets to decoys, for small data sets. 25137014 5 18 gly glycopeptide 1078:1089 arg2 glycopeptide 1078:1089 the glycopeptide data set 1074:1098 the glycopeptide data set 1074:1098 Nonetheless, this approach is not optimal in measuring the confidence of N-linked glycopeptide matches, because the glycopeptide data set is considerably smaller compared to that of peptides, and the requirement of a consensus sequence for N-glycosylation further limits the number of possible decoy glycopeptides tested in a database search. 25137014 5 19 theme matches 1057:1063 arg1 confidence 1021:1030 the confidence 1017:1030 the confidence of N-linked glycopeptide matches 1017:1063 Nonetheless, this approach is not optimal in measuring the confidence of N-linked glycopeptide matches, because the glycopeptide data set is considerably smaller compared to that of peptides, and the requirement of a consensus sequence for N-glycosylation further limits the number of possible decoy glycopeptides tested in a database search. 25137014 8 20 dep along 1646:1650 arg1 with 1652:1655 with 1652:1655 with 1652:1655 The decoys, along with target glycopeptides, are scored against the ETD data, from which FDRs can be calculated accurately based on the number of decoy matches and the ratio of the number of targets to decoys, for small data sets. 25137014 0 21 theme small 143:147 arg1 sets 154:157 small data sets 143:157 small data sets 143:157 New glycoproteomics software, GlycoPep Evaluator, generates decoy glycopeptides de novo and enables accurate false discovery rate analysis for small data sets. 25137014 4 22 theme decoy 884:888 arg1 database 890:897 a decoy database 882:897 a decoy database that is created based on the target protein sequence database 882:959 A common approach to calculate FDRs for glycopeptide analysis, adopted from the target-decoy strategy in proteomics, employs a decoy database that is created based on the target protein sequence database. 25137014 5 23 theme decoy 1256:1260 arg1 glycopeptides 1262:1274 possible decoy glycopeptides 1247:1274 possible decoy glycopeptides tested in a database search 1247:1302 Nonetheless, this approach is not optimal in measuring the confidence of N-linked glycopeptide matches, because the glycopeptide data set is considerably smaller compared to that of peptides, and the requirement of a consensus sequence for N-glycosylation further limits the number of possible decoy glycopeptides tested in a database search. 25137014 4 24 theme sequence 943:950 arg1 database 952:959 the target protein sequence database 924:959 the target protein sequence database 924:959 A common approach to calculate FDRs for glycopeptide analysis, adopted from the target-decoy strategy in proteomics, employs a decoy database that is created based on the target protein sequence database. 25137014 6 25 theme automated 1358:1366 arg1 assignments 1381:1391 automated glycopeptide assignments 1358:1391 automated glycopeptide assignments 1358:1391 To address the need to accurately determine FDRs for automated glycopeptide assignments, we developed GlycoPep Evaluator (GPE), a tool that helps to measure FDRs in identifying glycopeptides without using a decoy database. 25137014 4 26 from strategy 850:857 arg1 proteomics 862:871 proteomics 862:871 proteomics 862:871 A common approach to calculate FDRs for glycopeptide analysis, adopted from the target-decoy strategy in proteomics, employs a decoy database that is created based on the target protein sequence database. 25137014 5 27 link N-linked 1035:1042 arg1 matches 1057:1063 N-linked glycopeptide matches 1035:1063 N-linked glycopeptide matches 1035:1063 Nonetheless, this approach is not optimal in measuring the confidence of N-linked glycopeptide matches, because the glycopeptide data set is considerably smaller compared to that of peptides, and the requirement of a consensus sequence for N-glycosylation further limits the number of possible decoy glycopeptides tested in a database search. 25137014 0 28 gly glycopeptides 66:78 arg2 glycopeptides 66:78 decoy glycopeptides 60:78 decoy glycopeptides 60:78 New glycoproteomics software, GlycoPep Evaluator, generates decoy glycopeptides de novo and enables accurate false discovery rate analysis for small data sets. 25137014 2 29 theme transfer 529:536 arg1 ETD 552:554 ETD 552:554 ETD 552:554 In order to obtain site-specific protein glycosylation information, intact glycopeptides, with the glycan attached to the peptide sequence, are characterized by tandem mass spectrometry (MS/MS) methods such as collision-induced dissociation (CID) and electron transfer dissociation (ETD). 25137014 2 29 theme transfer 529:536 arg1 dissociation 538:549 electron transfer dissociation 520:549 electron transfer dissociation (ETD) 520:555 In order to obtain site-specific protein glycosylation information, intact glycopeptides, with the glycan attached to the peptide sequence, are characterized by tandem mass spectrometry (MS/MS) methods such as collision-induced dissociation (CID) and electron transfer dissociation (ETD). 25137014 9 30 theme search 1925:1930 arg1 engine 1932:1937 any search engine 1921:1937 any search engine that interprets ETD data of N-linked glycopeptides 1921:1988 GPE is freely accessible for download and can work with any search engine that interprets ETD data of N-linked glycopeptides. 25137014 0 31 theme accurate 100:107 arg1 analysis 130:137 accurate false discovery rate analysis 100:137 accurate false discovery rate analysis for small data sets 100:157 New glycoproteomics software, GlycoPep Evaluator, generates decoy glycopeptides de novo and enables accurate false discovery rate analysis for small data sets. 25137014 5 32 theme glycopeptide 1078:1089 arg1 set 1096:1098 the glycopeptide data set 1074:1098 the glycopeptide data set 1074:1098 Nonetheless, this approach is not optimal in measuring the confidence of N-linked glycopeptide matches, because the glycopeptide data set is considerably smaller compared to that of peptides, and the requirement of a consensus sequence for N-glycosylation further limits the number of possible decoy glycopeptides tested in a database search. 25137014 5 32 theme glycopeptide 1078:1089 arg1 smaller 1116:1122 smaller 1116:1122 smaller 1116:1122 Nonetheless, this approach is not optimal in measuring the confidence of N-linked glycopeptide matches, because the glycopeptide data set is considerably smaller compared to that of peptides, and the requirement of a consensus sequence for N-glycosylation further limits the number of possible decoy glycopeptides tested in a database search. 25137014 0 33 theme New 0:2 arg1 software 20:27 New glycoproteomics software 0:27 New glycoproteomics software 0:27 New glycoproteomics software, GlycoPep Evaluator, generates decoy glycopeptides de novo and enables accurate false discovery rate analysis for small data sets. 25137014 0 33 theme New 0:2 arg1 Evaluator 39:47 GlycoPep Evaluator 30:47 GlycoPep Evaluator 30:47 New glycoproteomics software, GlycoPep Evaluator, generates decoy glycopeptides de novo and enables accurate false discovery rate analysis for small data sets. 25137014 8 34 theme matches 1786:1792 arg1 number 1770:1775 the number 1766:1775 the number of decoy matches and the ratio of the number of targets to decoys, for small data sets 1766:1862 The decoys, along with target glycopeptides, are scored against the ETD data, from which FDRs can be calculated accurately based on the number of decoy matches and the ratio of the number of targets to decoys, for small data sets. 25137014 9 35 theme ETD 1955:1957 arg1 data 1959:1962 ETD data 1955:1962 ETD data of N-linked glycopeptides 1955:1988 GPE is freely accessible for download and can work with any search engine that interprets ETD data of N-linked glycopeptides. 25137014 2 36 theme spectrometry 442:453 arg1 methods 463:469 tandem mass spectrometry (MS/MS) methods 430:469 tandem mass spectrometry (MS/MS) methods such as collision-induced dissociation (CID) and electron transfer dissociation (ETD) 430:555 In order to obtain site-specific protein glycosylation information, intact glycopeptides, with the glycan attached to the peptide sequence, are characterized by tandem mass spectrometry (MS/MS) methods such as collision-induced dissociation (CID) and electron transfer dissociation (ETD). 25137014 2 36 theme spectrometry 442:453 arg1 dissociation 538:549 electron transfer dissociation 520:549 electron transfer dissociation (ETD) 520:555 In order to obtain site-specific protein glycosylation information, intact glycopeptides, with the glycan attached to the peptide sequence, are characterized by tandem mass spectrometry (MS/MS) methods such as collision-induced dissociation (CID) and electron transfer dissociation (ETD). 25137014 2 36 theme spectrometry 442:453 arg1 dissociation 497:508 collision-induced dissociation 479:508 collision-induced dissociation (CID) 479:514 In order to obtain site-specific protein glycosylation information, intact glycopeptides, with the glycan attached to the peptide sequence, are characterized by tandem mass spectrometry (MS/MS) methods such as collision-induced dissociation (CID) and electron transfer dissociation (ETD). 25137014 6 37 theme GlycoPep 1407:1414 arg1 Evaluator 1416:1424 GlycoPep Evaluator 1407:1424 GlycoPep Evaluator (GPE) 1407:1430 To address the need to accurately determine FDRs for automated glycopeptide assignments, we developed GlycoPep Evaluator (GPE), a tool that helps to measure FDRs in identifying glycopeptides without using a decoy database. 25137014 6 37 theme GlycoPep 1407:1414 arg1 tool 1435:1438 a tool 1433:1438 a tool that helps to measure FDRs in identifying glycopeptides without using a decoy database 1433:1525 To address the need to accurately determine FDRs for automated glycopeptide assignments, we developed GlycoPep Evaluator (GPE), a tool that helps to measure FDRs in identifying glycopeptides without using a decoy database. 25137014 6 37 theme GlycoPep 1407:1414 arg1 GPE 1427:1429 GPE 1427:1429 GPE 1427:1429 To address the need to accurately determine FDRs for automated glycopeptide assignments, we developed GlycoPep Evaluator (GPE), a tool that helps to measure FDRs in identifying glycopeptides without using a decoy database. 25137014 7 38 theme target-to-decoy 1611:1625 arg1 ratio 1627:1631 a 1:20 target-to-decoy ratio 1604:1631 a 1:20 target-to-decoy ratio 1604:1631 GPE generates decoy glycopeptides de novo for every target glycopeptide, in a 1:20 target-to-decoy ratio. 25137014 0 39 theme decoy 60:64 arg1 glycopeptides 66:78 decoy glycopeptides 60:78 decoy glycopeptides 60:78 New glycoproteomics software, GlycoPep Evaluator, generates decoy glycopeptides de novo and enables accurate false discovery rate analysis for small data sets. 25137014 2 40 theme tandem 430:435 arg1 MS/MS 456:460 MS/MS 456:460 MS/MS 456:460 In order to obtain site-specific protein glycosylation information, intact glycopeptides, with the glycan attached to the peptide sequence, are characterized by tandem mass spectrometry (MS/MS) methods such as collision-induced dissociation (CID) and electron transfer dissociation (ETD). 25137014 2 40 theme tandem 430:435 arg1 spectrometry 442:453 tandem mass spectrometry 430:453 tandem mass spectrometry (MS/MS) methods such as collision-induced dissociation (CID) and electron transfer dissociation (ETD) 430:555 In order to obtain site-specific protein glycosylation information, intact glycopeptides, with the glycan attached to the peptide sequence, are characterized by tandem mass spectrometry (MS/MS) methods such as collision-induced dissociation (CID) and electron transfer dissociation (ETD). 25137014 0 41 theme GlycoPep 30:37 arg1 software 20:27 New glycoproteomics software 0:27 New glycoproteomics software 0:27 New glycoproteomics software, GlycoPep Evaluator, generates decoy glycopeptides de novo and enables accurate false discovery rate analysis for small data sets. 25137014 0 41 theme GlycoPep 30:37 arg1 Evaluator 39:47 GlycoPep Evaluator 30:47 GlycoPep Evaluator 30:47 New glycoproteomics software, GlycoPep Evaluator, generates decoy glycopeptides de novo and enables accurate false discovery rate analysis for small data sets. 25137014 7 42 gly glycopeptide 1587:1598 arg2 glycopeptide 1587:1598 every target glycopeptide 1574:1598 every target glycopeptide 1574:1598 GPE generates decoy glycopeptides de novo for every target glycopeptide, in a 1:20 target-to-decoy ratio. 25137014 5 43 gly glycopeptides 1262:1274 arg2 glycopeptides 1262:1274 possible decoy glycopeptides 1247:1274 possible decoy glycopeptides tested in a database search 1247:1302 Nonetheless, this approach is not optimal in measuring the confidence of N-linked glycopeptide matches, because the glycopeptide data set is considerably smaller compared to that of peptides, and the requirement of a consensus sequence for N-glycosylation further limits the number of possible decoy glycopeptides tested in a database search. 25137014 5 44 gly glycopeptide 1044:1055 arg2 glycopeptide 1044:1055 N-linked glycopeptide matches 1035:1063 N-linked glycopeptide matches 1035:1063 Nonetheless, this approach is not optimal in measuring the confidence of N-linked glycopeptide matches, because the glycopeptide data set is considerably smaller compared to that of peptides, and the requirement of a consensus sequence for N-glycosylation further limits the number of possible decoy glycopeptides tested in a database search. 25137014 3 45 located present 628:634 arg1 field 643:647 the field 639:647 the field 639:647 While several emerging automated tools are developed, no consensus is present in the field about the best way to determine the reliability of the tools and/or provide the false discovery rate (FDR). 25137014 3 45 located present 628:634 arg2 consensus 615:623 no consensus 612:623 no consensus 612:623 While several emerging automated tools are developed, no consensus is present in the field about the best way to determine the reliability of the tools and/or provide the false discovery rate (FDR). 25137014 5 46 theme sequence 1189:1196 arg1 requirement 1162:1172 the requirement 1158:1172 the requirement of a consensus sequence for N-glycosylation 1158:1216 Nonetheless, this approach is not optimal in measuring the confidence of N-linked glycopeptide matches, because the glycopeptide data set is considerably smaller compared to that of peptides, and the requirement of a consensus sequence for N-glycosylation further limits the number of possible decoy glycopeptides tested in a database search. 25137014 6 47 gly glycopeptide 1368:1379 arg2 glycopeptide 1368:1379 automated glycopeptide assignments 1358:1391 automated glycopeptide assignments 1358:1391 To address the need to accurately determine FDRs for automated glycopeptide assignments, we developed GlycoPep Evaluator (GPE), a tool that helps to measure FDRs in identifying glycopeptides without using a decoy database. 25137014 4 48 theme calculate 778:786 arg1 FDRs 788:791 calculate FDRs 778:791 calculate FDRs 778:791 A common approach to calculate FDRs for glycopeptide analysis, adopted from the target-decoy strategy in proteomics, employs a decoy database that is created based on the target protein sequence database. 25137014 2 49 theme peptide 391:397 arg1 sequence 399:406 the peptide sequence 387:406 the peptide sequence 387:406 In order to obtain site-specific protein glycosylation information, intact glycopeptides, with the glycan attached to the peptide sequence, are characterized by tandem mass spectrometry (MS/MS) methods such as collision-induced dissociation (CID) and electron transfer dissociation (ETD). 25137014 1 50 theme cellular 248:255 arg1 activities 257:266 numerous cellular activities 239:266 numerous cellular activities 239:266 Glycoproteins are biologically significant large molecules that participate in numerous cellular activities. 25137014 2 51 attach attached 375:382 arg1 sequence 399:406 the peptide sequence 387:406 the peptide sequence 387:406 In order to obtain site-specific protein glycosylation information, intact glycopeptides, with the glycan attached to the peptide sequence, are characterized by tandem mass spectrometry (MS/MS) methods such as collision-induced dissociation (CID) and electron transfer dissociation (ETD). 25137014 2 51 attach attached 375:382 arg2 glycan 368:373 the glycan 364:373 the glycan attached to the peptide sequence 364:406 In order to obtain site-specific protein glycosylation information, intact glycopeptides, with the glycan attached to the peptide sequence, are characterized by tandem mass spectrometry (MS/MS) methods such as collision-induced dissociation (CID) and electron transfer dissociation (ETD). 25137014 4 52 theme target-decoy 837:848 arg1 strategy 850:857 the target-decoy strategy 833:857 the target-decoy strategy in proteomics 833:871 A common approach to calculate FDRs for glycopeptide analysis, adopted from the target-decoy strategy in proteomics, employs a decoy database that is created based on the target protein sequence database. 25137014 9 53 theme glycopeptides 1976:1988 arg1 data 1959:1962 ETD data 1955:1962 ETD data of N-linked glycopeptides 1955:1988 GPE is freely accessible for download and can work with any search engine that interprets ETD data of N-linked glycopeptides. 25137014 2 54 theme glycosylation 310:322 arg1 information 324:334 site-specific protein glycosylation information 288:334 site-specific protein glycosylation information 288:334 In order to obtain site-specific protein glycosylation information, intact glycopeptides, with the glycan attached to the peptide sequence, are characterized by tandem mass spectrometry (MS/MS) methods such as collision-induced dissociation (CID) and electron transfer dissociation (ETD). 25137014 8 55 theme number 1815:1820 arg1 ratio 1802:1806 the ratio 1798:1806 the ratio of the number of targets to decoys, for small data sets 1798:1862 The decoys, along with target glycopeptides, are scored against the ETD data, from which FDRs can be calculated accurately based on the number of decoy matches and the ratio of the number of targets to decoys, for small data sets. 25137014 8 55 theme number 1815:1820 arg1 matches 1786:1792 decoy matches 1780:1792 decoy matches 1780:1792 The decoys, along with target glycopeptides, are scored against the ETD data, from which FDRs can be calculated accurately based on the number of decoy matches and the ratio of the number of targets to decoys, for small data sets. 25137014 2 56 theme site-specific 288:300 arg1 information 324:334 site-specific protein glycosylation information 288:334 site-specific protein glycosylation information 288:334 In order to obtain site-specific protein glycosylation information, intact glycopeptides, with the glycan attached to the peptide sequence, are characterized by tandem mass spectrometry (MS/MS) methods such as collision-induced dissociation (CID) and electron transfer dissociation (ETD). 25137014 8 57 theme target 1657:1662 arg1 glycopeptides 1664:1676 target glycopeptides 1657:1676 target glycopeptides 1657:1676 The decoys, along with target glycopeptides, are scored against the ETD data, from which FDRs can be calculated accurately based on the number of decoy matches and the ratio of the number of targets to decoys, for small data sets. 25137014 8 58 theme targets 1825:1831 arg1 number 1815:1820 the number 1811:1820 the number of targets 1811:1831 The decoys, along with target glycopeptides, are scored against the ETD data, from which FDRs can be calculated accurately based on the number of decoy matches and the ratio of the number of targets to decoys, for small data sets. 25137014 3 59 theme automated 581:589 arg1 tools 591:595 several emerging automated tools 564:595 several emerging automated tools 564:595 While several emerging automated tools are developed, no consensus is present in the field about the best way to determine the reliability of the tools and/or provide the false discovery rate (FDR). 25137014 7 60 gly glycopeptides 1548:1560 arg2 glycopeptides 1548:1560 decoy glycopeptides 1542:1560 decoy glycopeptides 1542:1560 GPE generates decoy glycopeptides de novo for every target glycopeptide, in a 1:20 target-to-decoy ratio. 25137014 0 61 theme rate 125:128 arg1 analysis 130:137 accurate false discovery rate analysis 100:137 accurate false discovery rate analysis for small data sets 100:157 New glycoproteomics software, GlycoPep Evaluator, generates decoy glycopeptides de novo and enables accurate false discovery rate analysis for small data sets. 25137014 3 62 theme several 564:570 arg1 tools 591:595 several emerging automated tools 564:595 several emerging automated tools 564:595 While several emerging automated tools are developed, no consensus is present in the field about the best way to determine the reliability of the tools and/or provide the false discovery rate (FDR). 25137014 1 63 theme large 203:207 arg1 molecules 209:217 biologically significant large molecules 178:217 biologically significant large molecules that participate in numerous cellular activities 178:266 Glycoproteins are biologically significant large molecules that participate in numerous cellular activities. 25137014 1 63 theme large 203:207 arg1 Glycoproteins 160:172 Glycoproteins 160:172 Glycoproteins 160:172 Glycoproteins are biologically significant large molecules that participate in numerous cellular activities. 25137014 8 64 gly glycopeptides 1664:1676 arg2 glycopeptides 1664:1676 target glycopeptides 1657:1676 target glycopeptides 1657:1676 The decoys, along with target glycopeptides, are scored against the ETD data, from which FDRs can be calculated accurately based on the number of decoy matches and the ratio of the number of targets to decoys, for small data sets. 25137014 3 65 theme discovery 735:743 arg1 rate 745:748 the false discovery rate 725:748 the false discovery rate (FDR) 725:754 While several emerging automated tools are developed, no consensus is present in the field about the best way to determine the reliability of the tools and/or provide the false discovery rate (FDR). 25137014 3 65 theme discovery 735:743 arg1 FDR 751:753 FDR 751:753 FDR 751:753 While several emerging automated tools are developed, no consensus is present in the field about the best way to determine the reliability of the tools and/or provide the false discovery rate (FDR). 25137014 6 66 gly glycopeptides 1482:1494 arg2 glycopeptides 1482:1494 glycopeptides 1482:1494 glycopeptides 1482:1494 To address the need to accurately determine FDRs for automated glycopeptide assignments, we developed GlycoPep Evaluator (GPE), a tool that helps to measure FDRs in identifying glycopeptides without using a decoy database. 25137014 7 67 theme target 1580:1585 arg1 glycopeptide 1587:1598 every target glycopeptide 1574:1598 every target glycopeptide 1574:1598 GPE generates decoy glycopeptides de novo for every target glycopeptide, in a 1:20 target-to-decoy ratio. 25137014 8 68 theme data 1854:1857 arg1 sets 1859:1862 small data sets 1848:1862 small data sets 1848:1862 The decoys, along with target glycopeptides, are scored against the ETD data, from which FDRs can be calculated accurately based on the number of decoy matches and the ratio of the number of targets to decoys, for small data sets. 25137014 5 69 theme possible 1247:1254 arg1 glycopeptides 1262:1274 possible decoy glycopeptides 1247:1274 possible decoy glycopeptides tested in a database search 1247:1302 Nonetheless, this approach is not optimal in measuring the confidence of N-linked glycopeptide matches, because the glycopeptide data set is considerably smaller compared to that of peptides, and the requirement of a consensus sequence for N-glycosylation further limits the number of possible decoy glycopeptides tested in a database search. 25137014 3 70 attach present 628:634 arg2 consensus 615:623 no consensus 612:623 no consensus 612:623 While several emerging automated tools are developed, no consensus is present in the field about the best way to determine the reliability of the tools and/or provide the false discovery rate (FDR). 25137014 3 70 attach present 628:634 arg1 field 643:647 the field 639:647 the field 639:647 While several emerging automated tools are developed, no consensus is present in the field about the best way to determine the reliability of the tools and/or provide the false discovery rate (FDR). 25137014 5 71 theme glycopeptides 1262:1274 arg1 number 1237:1242 the number 1233:1242 the number of possible decoy glycopeptides tested in a database search 1233:1302 Nonetheless, this approach is not optimal in measuring the confidence of N-linked glycopeptide matches, because the glycopeptide data set is considerably smaller compared to that of peptides, and the requirement of a consensus sequence for N-glycosylation further limits the number of possible decoy glycopeptides tested in a database search. 25137014 6 72 theme glycopeptide 1368:1379 arg1 assignments 1381:1391 automated glycopeptide assignments 1358:1391 automated glycopeptide assignments 1358:1391 To address the need to accurately determine FDRs for automated glycopeptide assignments, we developed GlycoPep Evaluator (GPE), a tool that helps to measure FDRs in identifying glycopeptides without using a decoy database. 25137014 7 73 theme decoy 1542:1546 arg1 glycopeptides 1548:1560 decoy glycopeptides 1542:1560 decoy glycopeptides 1542:1560 GPE generates decoy glycopeptides de novo for every target glycopeptide, in a 1:20 target-to-decoy ratio. 25137014 4 74 theme protein 935:941 arg1 database 952:959 the target protein sequence database 924:959 the target protein sequence database 924:959 A common approach to calculate FDRs for glycopeptide analysis, adopted from the target-decoy strategy in proteomics, employs a decoy database that is created based on the target protein sequence database. 25137014 2 75 with glycopeptides 344:356 arg1 glycan 368:373 the glycan 364:373 the glycan attached to the peptide sequence 364:406 In order to obtain site-specific protein glycosylation information, intact glycopeptides, with the glycan attached to the peptide sequence, are characterized by tandem mass spectrometry (MS/MS) methods such as collision-induced dissociation (CID) and electron transfer dissociation (ETD). 25137014 0 76 theme false 109:113 arg1 rate 125:128 false discovery rate 109:128 accurate false discovery rate analysis for small data sets 100:157 New glycoproteomics software, GlycoPep Evaluator, generates decoy glycopeptides de novo and enables accurate false discovery rate analysis for small data sets. 25137014 2 77 theme electron 520:527 arg1 ETD 552:554 ETD 552:554 ETD 552:554 In order to obtain site-specific protein glycosylation information, intact glycopeptides, with the glycan attached to the peptide sequence, are characterized by tandem mass spectrometry (MS/MS) methods such as collision-induced dissociation (CID) and electron transfer dissociation (ETD). 25137014 2 77 theme electron 520:527 arg1 dissociation 538:549 electron transfer dissociation 520:549 electron transfer dissociation (ETD) 520:555 In order to obtain site-specific protein glycosylation information, intact glycopeptides, with the glycan attached to the peptide sequence, are characterized by tandem mass spectrometry (MS/MS) methods such as collision-induced dissociation (CID) and electron transfer dissociation (ETD). 25137014 3 78 from present 628:634 arg1 field 643:647 the field 639:647 the field 639:647 While several emerging automated tools are developed, no consensus is present in the field about the best way to determine the reliability of the tools and/or provide the false discovery rate (FDR). 25137014 4 79 theme target 928:933 arg1 database 952:959 the target protein sequence database 924:959 the target protein sequence database 924:959 A common approach to calculate FDRs for glycopeptide analysis, adopted from the target-decoy strategy in proteomics, employs a decoy database that is created based on the target protein sequence database. 25137014 0 80 theme glycoproteomics 4:18 arg1 software 20:27 New glycoproteomics software 0:27 New glycoproteomics software 0:27 New glycoproteomics software, GlycoPep Evaluator, generates decoy glycopeptides de novo and enables accurate false discovery rate analysis for small data sets. 25137014 0 80 theme glycoproteomics 4:18 arg1 Evaluator 39:47 GlycoPep Evaluator 30:47 GlycoPep Evaluator 30:47 New glycoproteomics software, GlycoPep Evaluator, generates decoy glycopeptides de novo and enables accurate false discovery rate analysis for small data sets. 25137014 5 81 theme data 1091:1094 arg1 set 1096:1098 the glycopeptide data set 1074:1098 the glycopeptide data set 1074:1098 Nonetheless, this approach is not optimal in measuring the confidence of N-linked glycopeptide matches, because the glycopeptide data set is considerably smaller compared to that of peptides, and the requirement of a consensus sequence for N-glycosylation further limits the number of possible decoy glycopeptides tested in a database search. 25137014 5 81 theme data 1091:1094 arg1 smaller 1116:1122 smaller 1116:1122 smaller 1116:1122 Nonetheless, this approach is not optimal in measuring the confidence of N-linked glycopeptide matches, because the glycopeptide data set is considerably smaller compared to that of peptides, and the requirement of a consensus sequence for N-glycosylation further limits the number of possible decoy glycopeptides tested in a database search. 25137014 9 82 gly glycopeptides 1976:1988 arg2 glycopeptides 1976:1988 N-linked glycopeptides 1967:1988 N-linked glycopeptides 1967:1988 GPE is freely accessible for download and can work with any search engine that interprets ETD data of N-linked glycopeptides. 25137014 5 83 theme glycopeptide 1044:1055 arg1 matches 1057:1063 N-linked glycopeptide matches 1035:1063 N-linked glycopeptide matches 1035:1063 Nonetheless, this approach is not optimal in measuring the confidence of N-linked glycopeptide matches, because the glycopeptide data set is considerably smaller compared to that of peptides, and the requirement of a consensus sequence for N-glycosylation further limits the number of possible decoy glycopeptides tested in a database search. 25137014 4 84 gly glycopeptide 797:808 arg2 glycopeptide 797:808 glycopeptide analysis 797:817 glycopeptide analysis 797:817 A common approach to calculate FDRs for glycopeptide analysis, adopted from the target-decoy strategy in proteomics, employs a decoy database that is created based on the target protein sequence database. 25137014 8 85 theme decoy 1780:1784 arg1 matches 1786:1792 decoy matches 1780:1792 decoy matches 1780:1792 The decoys, along with target glycopeptides, are scored against the ETD data, from which FDRs can be calculated accurately based on the number of decoy matches and the ratio of the number of targets to decoys, for small data sets. 25137014 5 86 theme database 1288:1295 arg1 search 1297:1302 a database search 1286:1302 a database search 1286:1302 Nonetheless, this approach is not optimal in measuring the confidence of N-linked glycopeptide matches, because the glycopeptide data set is considerably smaller compared to that of peptides, and the requirement of a consensus sequence for N-glycosylation further limits the number of possible decoy glycopeptides tested in a database search. 25137014 2 87 theme mass 437:440 arg1 MS/MS 456:460 MS/MS 456:460 MS/MS 456:460 In order to obtain site-specific protein glycosylation information, intact glycopeptides, with the glycan attached to the peptide sequence, are characterized by tandem mass spectrometry (MS/MS) methods such as collision-induced dissociation (CID) and electron transfer dissociation (ETD). 25137014 2 87 theme mass 437:440 arg1 spectrometry 442:453 tandem mass spectrometry 430:453 tandem mass spectrometry (MS/MS) methods such as collision-induced dissociation (CID) and electron transfer dissociation (ETD) 430:555 In order to obtain site-specific protein glycosylation information, intact glycopeptides, with the glycan attached to the peptide sequence, are characterized by tandem mass spectrometry (MS/MS) methods such as collision-induced dissociation (CID) and electron transfer dissociation (ETD). 25137014 2 88 theme collision-induced 479:495 arg1 CID 511:513 CID 511:513 CID 511:513 In order to obtain site-specific protein glycosylation information, intact glycopeptides, with the glycan attached to the peptide sequence, are characterized by tandem mass spectrometry (MS/MS) methods such as collision-induced dissociation (CID) and electron transfer dissociation (ETD). 25137014 2 88 theme collision-induced 479:495 arg1 dissociation 497:508 collision-induced dissociation 479:508 collision-induced dissociation (CID) 479:514 In order to obtain site-specific protein glycosylation information, intact glycopeptides, with the glycan attached to the peptide sequence, are characterized by tandem mass spectrometry (MS/MS) methods such as collision-induced dissociation (CID) and electron transfer dissociation (ETD). 25137014 9 89 theme N-linked 1967:1974 arg1 glycopeptides 1976:1988 N-linked glycopeptides 1967:1988 N-linked glycopeptides 1967:1988 GPE is freely accessible for download and can work with any search engine that interprets ETD data of N-linked glycopeptides. 25137014 4 90 theme glycopeptide 797:808 arg1 analysis 810:817 glycopeptide analysis 797:817 glycopeptide analysis 797:817 A common approach to calculate FDRs for glycopeptide analysis, adopted from the target-decoy strategy in proteomics, employs a decoy database that is created based on the target protein sequence database. 25137014 3 91 theme best 659:662 arg1 way 664:666 the best way 655:666 the best way to determine the reliability of the tools and/or provide the false discovery rate (FDR) 655:754 While several emerging automated tools are developed, no consensus is present in the field about the best way to determine the reliability of the tools and/or provide the false discovery rate (FDR). 25137014 4 92 theme common 759:764 arg1 approach 766:773 A common approach 757:773 A common approach 757:773 A common approach to calculate FDRs for glycopeptide analysis, adopted from the target-decoy strategy in proteomics, employs a decoy database that is created based on the target protein sequence database. 25137014 1 93 theme numerous 239:246 arg1 activities 257:266 numerous cellular activities 239:266 numerous cellular activities 239:266 Glycoproteins are biologically significant large molecules that participate in numerous cellular activities. 25137014 2 94 gly glycopeptides 344:356 arg2 glycopeptides 344:356 intact glycopeptides 337:356 intact glycopeptides 337:356 In order to obtain site-specific protein glycosylation information, intact glycopeptides, with the glycan attached to the peptide sequence, are characterized by tandem mass spectrometry (MS/MS) methods such as collision-induced dissociation (CID) and electron transfer dissociation (ETD). 25137014 9 95 link N-linked 1967:1974 arg1 glycopeptides 1976:1988 N-linked glycopeptides 1967:1988 N-linked glycopeptides 1967:1988 GPE is freely accessible for download and can work with any search engine that interprets ETD data of N-linked glycopeptides. 26401918 6 0 theme complementary 1068:1080 arg1 manner 1061:1066 a manner 1059:1066 a manner complementary to that with conventional native chemical ligation-desulfurization strategies 1059:1158 The chemoselective activation and coupling of C-terminal peptidyl Gly thioacids with the N-terminus of an unprotected peptide provide ligated peptides directly in a manner complementary to that with conventional native chemical ligation-desulfurization strategies. 26401918 1 1 gly glycoprotein 206:217 arg1 factor 174:179 Human granulocyte colony-stimulating factor 137:179 Human granulocyte colony-stimulating factor (G-CSF) 137:187 Human granulocyte colony-stimulating factor (G-CSF) is an endogenous glycoprotein involved in hematopoiesis. 26401918 1 1 gly glycoprotein 206:217 arg1 glycoprotein 206:217 an endogenous glycoprotein 192:217 an endogenous glycoprotein involved in hematopoiesis 192:243 Human granulocyte colony-stimulating factor (G-CSF) is an endogenous glycoprotein involved in hematopoiesis. 26401918 3 2 from Thr133 531:536 arg1 purpose 494:500 the purpose 490:500 the purpose of O-linked glycosylation at Thr133 490:536 Despite their comparable therapeutic potential, the purpose of O-linked glycosylation at Thr133 remains a subject of controversy. 26401918 6 3 theme chemical 1115:1122 arg1 strategies 1149:1158 conventional native chemical ligation-desulfurization strategies 1095:1158 conventional native chemical ligation-desulfurization strategies 1095:1158 The chemoselective activation and coupling of C-terminal peptidyl Gly thioacids with the N-terminus of an unprotected peptide provide ligated peptides directly in a manner complementary to that with conventional native chemical ligation-desulfurization strategies. 26401918 0 4 theme Large 97:101 arg1 Peptides 127:134 Large, Side-Chain-Unprotected Peptides 97:134 Large, Side-Chain-Unprotected Peptides 97:134 Fully Synthetic Granulocyte Colony-Stimulating Factor Enabled by Isonitrile-Mediated Coupling of Large, Side-Chain-Unprotected Peptides. 26401918 4 5 with glycoforms 711:720 arg1 site-selectivity 727:742 site-selectivity 727:742 site-selectivity 727:742 In light of this, we have developed a synthetic platform to prepare G-CSF aglycone with the goal of enabling access to native and designed glycoforms with site-selectivity and glycan homogeneity. 26401918 4 5 with glycoforms 711:720 arg1 homogeneity 755:765 glycan homogeneity 748:765 glycan homogeneity 748:765 In light of this, we have developed a synthetic platform to prepare G-CSF aglycone with the goal of enabling access to native and designed glycoforms with site-selectivity and glycan homogeneity. 26401918 7 6 theme total 1253:1257 arg1 synthesis 1259:1267 the convergent total synthesis 1238:1267 the convergent total synthesis of G-CSF aglycone 1238:1285 Herein, we describe the details and application of this method as it enabled the convergent total synthesis of G-CSF aglycone. 26401918 2 7 theme chemotherapeutic 414:429 arg1 treatment 431:439 chemotherapeutic treatment 414:439 chemotherapeutic treatment 414:439 Natively glycosylated and nonglycosylated recombinant forms, lenograstim and filgrastim, respectively, are used clinically to manage neutropenia in patients undergoing chemotherapeutic treatment. 26401918 6 8 theme native 1108:1113 arg1 strategies 1149:1158 conventional native chemical ligation-desulfurization strategies 1095:1158 conventional native chemical ligation-desulfurization strategies 1095:1158 The chemoselective activation and coupling of C-terminal peptidyl Gly thioacids with the N-terminus of an unprotected peptide provide ligated peptides directly in a manner complementary to that with conventional native chemical ligation-desulfurization strategies. 26401918 0 9 theme Peptides 127:134 arg1 Coupling 85:92 Isonitrile-Mediated Coupling 65:92 Isonitrile-Mediated Coupling of Large, Side-Chain-Unprotected Peptides 65:134 Fully Synthetic Granulocyte Colony-Stimulating Factor Enabled by Isonitrile-Mediated Coupling of Large, Side-Chain-Unprotected Peptides. 26401918 6 10 theme unprotected 1002:1012 arg1 peptide 1014:1020 an unprotected peptide 999:1020 an unprotected peptide 999:1020 The chemoselective activation and coupling of C-terminal peptidyl Gly thioacids with the N-terminus of an unprotected peptide provide ligated peptides directly in a manner complementary to that with conventional native chemical ligation-desulfurization strategies. 26401918 2 11 from neutropenia 379:389 arg1 patients 394:401 patients 394:401 patients undergoing chemotherapeutic treatment 394:439 Natively glycosylated and nonglycosylated recombinant forms, lenograstim and filgrastim, respectively, are used clinically to manage neutropenia in patients undergoing chemotherapeutic treatment. 26401918 6 12 theme conventional 1095:1106 arg1 strategies 1149:1158 conventional native chemical ligation-desulfurization strategies 1095:1158 conventional native chemical ligation-desulfurization strategies 1095:1158 The chemoselective activation and coupling of C-terminal peptidyl Gly thioacids with the N-terminus of an unprotected peptide provide ligated peptides directly in a manner complementary to that with conventional native chemical ligation-desulfurization strategies. 26401918 5 13 theme large 809:813 arg1 sequence 834:841 a relatively large, aggregation-prone sequence 796:841 a relatively large, aggregation-prone sequence 796:841 To address the synthesis of a relatively large, aggregation-prone sequence, we advanced an isonitrile-mediated ligation method. 26401918 3 14 link O-linked 505:512 arg1 glycosylation 514:526 O-linked glycosylation 505:526 O-linked glycosylation 505:526 Despite their comparable therapeutic potential, the purpose of O-linked glycosylation at Thr133 remains a subject of controversy. 26401918 4 15 theme glycan 748:753 arg1 homogeneity 755:765 glycan homogeneity 748:765 glycan homogeneity 748:765 In light of this, we have developed a synthetic platform to prepare G-CSF aglycone with the goal of enabling access to native and designed glycoforms with site-selectivity and glycan homogeneity. 26401918 1 16 theme endogenous 195:204 arg1 factor 174:179 Human granulocyte colony-stimulating factor 137:179 Human granulocyte colony-stimulating factor (G-CSF) 137:187 Human granulocyte colony-stimulating factor (G-CSF) is an endogenous glycoprotein involved in hematopoiesis. 26401918 1 16 theme endogenous 195:204 arg1 glycoprotein 206:217 an endogenous glycoprotein 192:217 an endogenous glycoprotein involved in hematopoiesis 192:243 Human granulocyte colony-stimulating factor (G-CSF) is an endogenous glycoprotein involved in hematopoiesis. 26401918 0 17 theme Synthetic 6:14 arg1 Factor 47:52 Fully Synthetic Granulocyte Colony-Stimulating Factor 0:52 Fully Synthetic Granulocyte Colony-Stimulating Factor 0:52 Fully Synthetic Granulocyte Colony-Stimulating Factor Enabled by Isonitrile-Mediated Coupling of Large, Side-Chain-Unprotected Peptides. 26401918 7 18 dep details 1185:1191 arg1 the 1181:1183 the 1181:1183 the 1181:1183 Herein, we describe the details and application of this method as it enabled the convergent total synthesis of G-CSF aglycone. 26401918 3 19 theme O-linked 505:512 arg1 glycosylation 514:526 O-linked glycosylation 505:526 O-linked glycosylation 505:526 Despite their comparable therapeutic potential, the purpose of O-linked glycosylation at Thr133 remains a subject of controversy. 26401918 6 20 theme peptide 1014:1020 arg1 N-terminus 985:994 the N-terminus 981:994 the N-terminus of an unprotected peptide 981:1020 The chemoselective activation and coupling of C-terminal peptidyl Gly thioacids with the N-terminus of an unprotected peptide provide ligated peptides directly in a manner complementary to that with conventional native chemical ligation-desulfurization strategies. 26401918 7 21 theme method 1217:1222 arg1 application 1197:1207 application 1197:1207 application 1197:1207 Herein, we describe the details and application of this method as it enabled the convergent total synthesis of G-CSF aglycone. 26401918 7 21 theme method 1217:1222 arg1 details 1185:1191 details 1185:1191 details 1185:1191 Herein, we describe the details and application of this method as it enabled the convergent total synthesis of G-CSF aglycone. 26401918 0 22 dep Large 97:101 arg1 Side-Chain-Unprotected 104:125 Side-Chain-Unprotected 104:125 Side-Chain-Unprotected 104:125 Fully Synthetic Granulocyte Colony-Stimulating Factor Enabled by Isonitrile-Mediated Coupling of Large, Side-Chain-Unprotected Peptides. 26401918 3 23 theme glycosylation 514:526 arg1 purpose 494:500 the purpose 490:500 the purpose of O-linked glycosylation at Thr133 490:536 Despite their comparable therapeutic potential, the purpose of O-linked glycosylation at Thr133 remains a subject of controversy. 26401918 0 24 theme Colony-Stimulating 28:45 arg1 Factor 47:52 Fully Synthetic Granulocyte Colony-Stimulating Factor 0:52 Fully Synthetic Granulocyte Colony-Stimulating Factor 0:52 Fully Synthetic Granulocyte Colony-Stimulating Factor Enabled by Isonitrile-Mediated Coupling of Large, Side-Chain-Unprotected Peptides. 26401918 7 25 theme convergent 1242:1251 arg1 synthesis 1259:1267 the convergent total synthesis 1238:1267 the convergent total synthesis of G-CSF aglycone 1238:1285 Herein, we describe the details and application of this method as it enabled the convergent total synthesis of G-CSF aglycone. 26401918 0 26 theme Granulocyte 16:26 arg1 Factor 47:52 Fully Synthetic Granulocyte Colony-Stimulating Factor 0:52 Fully Synthetic Granulocyte Colony-Stimulating Factor 0:52 Fully Synthetic Granulocyte Colony-Stimulating Factor Enabled by Isonitrile-Mediated Coupling of Large, Side-Chain-Unprotected Peptides. 26401918 4 27 theme G-CSF 640:644 arg1 aglycone 646:653 G-CSF aglycone 640:653 G-CSF aglycone 640:653 In light of this, we have developed a synthetic platform to prepare G-CSF aglycone with the goal of enabling access to native and designed glycoforms with site-selectivity and glycan homogeneity. 26401918 6 28 theme C-terminal 942:951 arg1 thioacids 966:974 C-terminal peptidyl Gly thioacids 942:974 C-terminal peptidyl Gly thioacids with the N-terminus of an unprotected peptide 942:1020 The chemoselective activation and coupling of C-terminal peptidyl Gly thioacids with the N-terminus of an unprotected peptide provide ligated peptides directly in a manner complementary to that with conventional native chemical ligation-desulfurization strategies. 26401918 1 29 theme Human 137:141 arg1 factor 174:179 Human granulocyte colony-stimulating factor 137:179 Human granulocyte colony-stimulating factor (G-CSF) 137:187 Human granulocyte colony-stimulating factor (G-CSF) is an endogenous glycoprotein involved in hematopoiesis. 26401918 1 29 theme Human 137:141 arg1 glycoprotein 206:217 an endogenous glycoprotein 192:217 an endogenous glycoprotein involved in hematopoiesis 192:243 Human granulocyte colony-stimulating factor (G-CSF) is an endogenous glycoprotein involved in hematopoiesis. 26401918 1 29 theme Human 137:141 arg1 G-CSF 182:186 G-CSF 182:186 G-CSF 182:186 Human granulocyte colony-stimulating factor (G-CSF) is an endogenous glycoprotein involved in hematopoiesis. 26401918 6 30 dep activation 915:924 arg1 The 896:898 The 896:898 The 896:898 The chemoselective activation and coupling of C-terminal peptidyl Gly thioacids with the N-terminus of an unprotected peptide provide ligated peptides directly in a manner complementary to that with conventional native chemical ligation-desulfurization strategies. 26401918 4 31 theme native 691:696 arg1 glycoforms 711:720 native and designed glycoforms 691:720 native and designed glycoforms with site-selectivity and glycan homogeneity 691:765 In light of this, we have developed a synthetic platform to prepare G-CSF aglycone with the goal of enabling access to native and designed glycoforms with site-selectivity and glycan homogeneity. 26401918 7 32 theme G-CSF 1272:1276 arg1 aglycone 1278:1285 G-CSF aglycone 1272:1285 G-CSF aglycone 1272:1285 Herein, we describe the details and application of this method as it enabled the convergent total synthesis of G-CSF aglycone. 26401918 6 33 theme thioacids 966:974 arg1 coupling 930:937 coupling 930:937 coupling 930:937 The chemoselective activation and coupling of C-terminal peptidyl Gly thioacids with the N-terminus of an unprotected peptide provide ligated peptides directly in a manner complementary to that with conventional native chemical ligation-desulfurization strategies. 26401918 6 33 theme thioacids 966:974 arg1 activation 915:924 chemoselective activation 900:924 chemoselective activation 900:924 The chemoselective activation and coupling of C-terminal peptidyl Gly thioacids with the N-terminus of an unprotected peptide provide ligated peptides directly in a manner complementary to that with conventional native chemical ligation-desulfurization strategies. 26401918 6 34 with thioacids 966:974 arg1 N-terminus 985:994 the N-terminus 981:994 the N-terminus of an unprotected peptide 981:1020 The chemoselective activation and coupling of C-terminal peptidyl Gly thioacids with the N-terminus of an unprotected peptide provide ligated peptides directly in a manner complementary to that with conventional native chemical ligation-desulfurization strategies. 26401918 5 35 theme isonitrile-mediated 859:877 arg1 method 888:893 an isonitrile-mediated ligation method 856:893 an isonitrile-mediated ligation method 856:893 To address the synthesis of a relatively large, aggregation-prone sequence, we advanced an isonitrile-mediated ligation method. 26401918 7 36 theme aglycone 1278:1285 arg1 synthesis 1259:1267 the convergent total synthesis 1238:1267 the convergent total synthesis of G-CSF aglycone 1238:1285 Herein, we describe the details and application of this method as it enabled the convergent total synthesis of G-CSF aglycone. 26401918 6 37 theme Gly 962:964 arg1 thioacids 966:974 C-terminal peptidyl Gly thioacids 942:974 C-terminal peptidyl Gly thioacids with the N-terminus of an unprotected peptide 942:1020 The chemoselective activation and coupling of C-terminal peptidyl Gly thioacids with the N-terminus of an unprotected peptide provide ligated peptides directly in a manner complementary to that with conventional native chemical ligation-desulfurization strategies. 26401918 2 38 theme recombinant 288:298 arg1 lenograstim 307:317 lenograstim 307:317 lenograstim 307:317 Natively glycosylated and nonglycosylated recombinant forms, lenograstim and filgrastim, respectively, are used clinically to manage neutropenia in patients undergoing chemotherapeutic treatment. 26401918 2 38 theme recombinant 288:298 arg1 forms 300:304 Natively glycosylated and nonglycosylated recombinant forms 246:304 Natively glycosylated and nonglycosylated recombinant forms 246:304 Natively glycosylated and nonglycosylated recombinant forms, lenograstim and filgrastim, respectively, are used clinically to manage neutropenia in patients undergoing chemotherapeutic treatment. 26401918 2 38 theme recombinant 288:298 arg1 filgrastim 323:332 filgrastim 323:332 filgrastim 323:332 Natively glycosylated and nonglycosylated recombinant forms, lenograstim and filgrastim, respectively, are used clinically to manage neutropenia in patients undergoing chemotherapeutic treatment. 26401918 4 39 theme designed 702:709 arg1 glycoforms 711:720 native and designed glycoforms 691:720 native and designed glycoforms with site-selectivity and glycan homogeneity 691:765 In light of this, we have developed a synthetic platform to prepare G-CSF aglycone with the goal of enabling access to native and designed glycoforms with site-selectivity and glycan homogeneity. 26401918 0 40 theme Isonitrile-Mediated 65:83 arg1 Coupling 85:92 Isonitrile-Mediated Coupling 65:92 Isonitrile-Mediated Coupling of Large, Side-Chain-Unprotected Peptides 65:134 Fully Synthetic Granulocyte Colony-Stimulating Factor Enabled by Isonitrile-Mediated Coupling of Large, Side-Chain-Unprotected Peptides. 26401918 6 41 theme peptidyl 953:960 arg1 thioacids 966:974 C-terminal peptidyl Gly thioacids 942:974 C-terminal peptidyl Gly thioacids with the N-terminus of an unprotected peptide 942:1020 The chemoselective activation and coupling of C-terminal peptidyl Gly thioacids with the N-terminus of an unprotected peptide provide ligated peptides directly in a manner complementary to that with conventional native chemical ligation-desulfurization strategies. 26401918 2 42 theme nonglycosylated 272:286 arg1 lenograstim 307:317 lenograstim 307:317 lenograstim 307:317 Natively glycosylated and nonglycosylated recombinant forms, lenograstim and filgrastim, respectively, are used clinically to manage neutropenia in patients undergoing chemotherapeutic treatment. 26401918 2 42 theme nonglycosylated 272:286 arg1 forms 300:304 Natively glycosylated and nonglycosylated recombinant forms 246:304 Natively glycosylated and nonglycosylated recombinant forms 246:304 Natively glycosylated and nonglycosylated recombinant forms, lenograstim and filgrastim, respectively, are used clinically to manage neutropenia in patients undergoing chemotherapeutic treatment. 26401918 2 42 theme nonglycosylated 272:286 arg1 filgrastim 323:332 filgrastim 323:332 filgrastim 323:332 Natively glycosylated and nonglycosylated recombinant forms, lenograstim and filgrastim, respectively, are used clinically to manage neutropenia in patients undergoing chemotherapeutic treatment. 26401918 1 43 theme granulocyte 143:153 arg1 factor 174:179 Human granulocyte colony-stimulating factor 137:179 Human granulocyte colony-stimulating factor (G-CSF) 137:187 Human granulocyte colony-stimulating factor (G-CSF) is an endogenous glycoprotein involved in hematopoiesis. 26401918 1 43 theme granulocyte 143:153 arg1 glycoprotein 206:217 an endogenous glycoprotein 192:217 an endogenous glycoprotein involved in hematopoiesis 192:243 Human granulocyte colony-stimulating factor (G-CSF) is an endogenous glycoprotein involved in hematopoiesis. 26401918 1 43 theme granulocyte 143:153 arg1 G-CSF 182:186 G-CSF 182:186 G-CSF 182:186 Human granulocyte colony-stimulating factor (G-CSF) is an endogenous glycoprotein involved in hematopoiesis. 26401918 2 44 gly nonglycosylated 272:286 arg1 lenograstim 307:317 lenograstim 307:317 lenograstim 307:317 Natively glycosylated and nonglycosylated recombinant forms, lenograstim and filgrastim, respectively, are used clinically to manage neutropenia in patients undergoing chemotherapeutic treatment. 26401918 2 44 gly nonglycosylated 272:286 arg1 forms 300:304 Natively glycosylated and nonglycosylated recombinant forms 246:304 Natively glycosylated and nonglycosylated recombinant forms 246:304 Natively glycosylated and nonglycosylated recombinant forms, lenograstim and filgrastim, respectively, are used clinically to manage neutropenia in patients undergoing chemotherapeutic treatment. 26401918 2 44 gly nonglycosylated 272:286 arg1 filgrastim 323:332 filgrastim 323:332 filgrastim 323:332 Natively glycosylated and nonglycosylated recombinant forms, lenograstim and filgrastim, respectively, are used clinically to manage neutropenia in patients undergoing chemotherapeutic treatment. 26401918 4 45 theme synthetic 610:618 arg1 platform 620:627 a synthetic platform 608:627 a synthetic platform to prepare G-CSF aglycone with the goal of enabling access to native and designed glycoforms with site-selectivity and glycan homogeneity 608:765 In light of this, we have developed a synthetic platform to prepare G-CSF aglycone with the goal of enabling access to native and designed glycoforms with site-selectivity and glycan homogeneity. 26401918 6 46 theme ligated 1030:1036 arg1 peptides 1038:1045 ligated peptides 1030:1045 ligated peptides 1030:1045 The chemoselective activation and coupling of C-terminal peptidyl Gly thioacids with the N-terminus of an unprotected peptide provide ligated peptides directly in a manner complementary to that with conventional native chemical ligation-desulfurization strategies. 26401918 2 47 theme glycosylated 255:266 arg1 lenograstim 307:317 lenograstim 307:317 lenograstim 307:317 Natively glycosylated and nonglycosylated recombinant forms, lenograstim and filgrastim, respectively, are used clinically to manage neutropenia in patients undergoing chemotherapeutic treatment. 26401918 2 47 theme glycosylated 255:266 arg1 forms 300:304 Natively glycosylated and nonglycosylated recombinant forms 246:304 Natively glycosylated and nonglycosylated recombinant forms 246:304 Natively glycosylated and nonglycosylated recombinant forms, lenograstim and filgrastim, respectively, are used clinically to manage neutropenia in patients undergoing chemotherapeutic treatment. 26401918 2 47 theme glycosylated 255:266 arg1 filgrastim 323:332 filgrastim 323:332 filgrastim 323:332 Natively glycosylated and nonglycosylated recombinant forms, lenograstim and filgrastim, respectively, are used clinically to manage neutropenia in patients undergoing chemotherapeutic treatment. 26401918 1 48 theme colony-stimulating 155:172 arg1 factor 174:179 Human granulocyte colony-stimulating factor 137:179 Human granulocyte colony-stimulating factor (G-CSF) 137:187 Human granulocyte colony-stimulating factor (G-CSF) is an endogenous glycoprotein involved in hematopoiesis. 26401918 1 48 theme colony-stimulating 155:172 arg1 glycoprotein 206:217 an endogenous glycoprotein 192:217 an endogenous glycoprotein involved in hematopoiesis 192:243 Human granulocyte colony-stimulating factor (G-CSF) is an endogenous glycoprotein involved in hematopoiesis. 26401918 1 48 theme colony-stimulating 155:172 arg1 G-CSF 182:186 G-CSF 182:186 G-CSF 182:186 Human granulocyte colony-stimulating factor (G-CSF) is an endogenous glycoprotein involved in hematopoiesis. 26401918 2 49 used used 353:356 arg2 filgrastim 323:332 filgrastim 323:332 filgrastim 323:332 Natively glycosylated and nonglycosylated recombinant forms, lenograstim and filgrastim, respectively, are used clinically to manage neutropenia in patients undergoing chemotherapeutic treatment. 26401918 2 49 used used 353:356 arg2 lenograstim 307:317 lenograstim 307:317 lenograstim 307:317 Natively glycosylated and nonglycosylated recombinant forms, lenograstim and filgrastim, respectively, are used clinically to manage neutropenia in patients undergoing chemotherapeutic treatment. 26401918 2 49 used used 353:356 arg2 forms 300:304 Natively glycosylated and nonglycosylated recombinant forms 246:304 Natively glycosylated and nonglycosylated recombinant forms 246:304 Natively glycosylated and nonglycosylated recombinant forms, lenograstim and filgrastim, respectively, are used clinically to manage neutropenia in patients undergoing chemotherapeutic treatment. 26401918 6 50 theme chemoselective 900:913 arg1 activation 915:924 chemoselective activation 900:924 chemoselective activation 900:924 The chemoselective activation and coupling of C-terminal peptidyl Gly thioacids with the N-terminus of an unprotected peptide provide ligated peptides directly in a manner complementary to that with conventional native chemical ligation-desulfurization strategies. 26401918 3 51 theme controversy 559:569 arg1 subject 548:554 a subject 546:554 a subject of controversy 546:569 Despite their comparable therapeutic potential, the purpose of O-linked glycosylation at Thr133 remains a subject of controversy. 26401918 2 52 gly glycosylated 255:266 arg1 lenograstim 307:317 lenograstim 307:317 lenograstim 307:317 Natively glycosylated and nonglycosylated recombinant forms, lenograstim and filgrastim, respectively, are used clinically to manage neutropenia in patients undergoing chemotherapeutic treatment. 26401918 2 52 gly glycosylated 255:266 arg1 forms 300:304 Natively glycosylated and nonglycosylated recombinant forms 246:304 Natively glycosylated and nonglycosylated recombinant forms 246:304 Natively glycosylated and nonglycosylated recombinant forms, lenograstim and filgrastim, respectively, are used clinically to manage neutropenia in patients undergoing chemotherapeutic treatment. 26401918 2 52 gly glycosylated 255:266 arg1 filgrastim 323:332 filgrastim 323:332 filgrastim 323:332 Natively glycosylated and nonglycosylated recombinant forms, lenograstim and filgrastim, respectively, are used clinically to manage neutropenia in patients undergoing chemotherapeutic treatment. 26401918 5 53 dep large 809:813 arg1 aggregation-prone 816:832 aggregation-prone 816:832 aggregation-prone 816:832 To address the synthesis of a relatively large, aggregation-prone sequence, we advanced an isonitrile-mediated ligation method. 26401918 5 54 theme sequence 834:841 arg1 synthesis 783:791 the synthesis 779:791 the synthesis of a relatively large, aggregation-prone sequence 779:841 To address the synthesis of a relatively large, aggregation-prone sequence, we advanced an isonitrile-mediated ligation method. 26401918 5 55 theme ligation 879:886 arg1 method 888:893 an isonitrile-mediated ligation method 856:893 an isonitrile-mediated ligation method 856:893 To address the synthesis of a relatively large, aggregation-prone sequence, we advanced an isonitrile-mediated ligation method. 26401918 4 56 theme this 584:587 arg1 light 575:579 light 575:579 light of this 575:587 In light of this, we have developed a synthetic platform to prepare G-CSF aglycone with the goal of enabling access to native and designed glycoforms with site-selectivity and glycan homogeneity. 26401918 3 57 theme comparable 456:465 arg1 potential 479:487 their comparable therapeutic potential 450:487 their comparable therapeutic potential 450:487 Despite their comparable therapeutic potential, the purpose of O-linked glycosylation at Thr133 remains a subject of controversy. 26401918 3 58 theme therapeutic 467:477 arg1 potential 479:487 their comparable therapeutic potential 450:487 their comparable therapeutic potential 450:487 Despite their comparable therapeutic potential, the purpose of O-linked glycosylation at Thr133 remains a subject of controversy. 26401918 6 59 theme ligation-desulfurization 1124:1147 arg1 strategies 1149:1158 conventional native chemical ligation-desulfurization strategies 1095:1158 conventional native chemical ligation-desulfurization strategies 1095:1158 The chemoselective activation and coupling of C-terminal peptidyl Gly thioacids with the N-terminus of an unprotected peptide provide ligated peptides directly in a manner complementary to that with conventional native chemical ligation-desulfurization strategies. 25288802 0 0 theme missense 75:82 arg1 mutants 84:90 missense mutants 75:90 missense mutants associated with hereditary phosphoglucomutase 1 deficiency 75:149 Compromised catalysis and potential folding defects in in vitro studies of missense mutants associated with hereditary phosphoglucomutase 1 deficiency. 25288802 6 1 theme dramatic 952:959 arg1 reductions 961:970 dramatic reductions 952:970 dramatic reductions in enzyme activity 952:989 In contrast, other missense variants are well behaved in solution, but show dramatic reductions in enzyme activity, with kcat/Km often <1.5% of wild-type. 25288802 9 2 theme protein 1395:1401 arg1 misfolding 1403:1412 protein misfolding 1395:1412 protein misfolding 1395:1412 Our results complement previous in vivo studies, which suggest that both protein misfolding and catalytic impairment may play a role in PGM1 deficiency. 25288802 6 3 theme % 1015:1015 arg1 kcat/Km 997:1003 kcat/Km 997:1003 kcat/Km often <1.5% of wild-type 997:1028 In contrast, other missense variants are well behaved in solution, but show dramatic reductions in enzyme activity, with kcat/Km often <1.5% of wild-type. 25288802 4 4 theme PGM1 610:613 arg1 mutants 615:621 the PGM1 mutants 606:621 the PGM1 mutants 606:621 The biochemical phenotypes of the PGM1 mutants cluster into two groups: those with compromised catalysis and those with possible folding defects. 25288802 5 5 theme decreased 806:814 arg1 expression 816:825 greatly decreased expression 798:825 greatly decreased expression of soluble protein and/or increased aggregation 798:873 Relative to the recombinant wild-type enzyme, certain missense mutants show greatly decreased expression of soluble protein and/or increased aggregation. 25288802 9 6 theme PGM1 1458:1461 arg1 deficiency 1463:1472 PGM1 deficiency 1458:1472 PGM1 deficiency 1458:1472 Our results complement previous in vivo studies, which suggest that both protein misfolding and catalytic impairment may play a role in PGM1 deficiency. 25288802 3 7 theme missense 528:535 arg1 mutations 537:545 13 missense mutations 525:545 13 missense mutations involved in PGM1 deficiency 525:573 We present here the first in vitro biochemical characterization of 13 missense mutations involved in PGM1 deficiency. 25288802 6 8 theme wild-type 1020:1028 arg1 kcat/Km 997:1003 kcat/Km 997:1003 kcat/Km often <1.5% of wild-type 997:1028 In contrast, other missense variants are well behaved in solution, but show dramatic reductions in enzyme activity, with kcat/Km often <1.5% of wild-type. 25288802 9 9 dep in 1354:1355 arg1 vivo 1357:1360 vivo 1357:1360 vivo 1357:1360 Our results complement previous in vivo studies, which suggest that both protein misfolding and catalytic impairment may play a role in PGM1 deficiency. 25288802 0 10 theme mutants 84:90 arg1 studies 64:70 in vitro studies 55:70 in vitro studies of missense mutants associated with hereditary phosphoglucomutase 1 deficiency 55:149 Compromised catalysis and potential folding defects in in vitro studies of missense mutants associated with hereditary phosphoglucomutase 1 deficiency. 25288802 9 11 theme previous 1345:1352 arg1 studies 1362:1368 previous in vivo studies 1345:1368 previous in vivo studies 1345:1368 Our results complement previous in vivo studies, which suggest that both protein misfolding and catalytic impairment may play a role in PGM1 deficiency. 25288802 2 12 theme disease 300:306 arg1 intolerance 363:373 exercise intolerance 354:373 exercise intolerance 354:373 Affected patients show multiple disease phenotypes, including dilated cardiomyopathy, exercise intolerance, and hepatopathy, reflecting the central role of the enzyme in glucose metabolism. 25288802 2 12 theme disease 300:306 arg1 hepatopathy 380:390 hepatopathy 380:390 hepatopathy 380:390 Affected patients show multiple disease phenotypes, including dilated cardiomyopathy, exercise intolerance, and hepatopathy, reflecting the central role of the enzyme in glucose metabolism. 25288802 2 12 theme disease 300:306 arg1 phenotypes 308:317 multiple disease phenotypes 291:317 multiple disease phenotypes 291:317 Affected patients show multiple disease phenotypes, including dilated cardiomyopathy, exercise intolerance, and hepatopathy, reflecting the central role of the enzyme in glucose metabolism. 25288802 2 12 theme disease 300:306 arg1 cardiomyopathy 338:351 dilated cardiomyopathy 330:351 dilated cardiomyopathy 330:351 Affected patients show multiple disease phenotypes, including dilated cardiomyopathy, exercise intolerance, and hepatopathy, reflecting the central role of the enzyme in glucose metabolism. 25288802 4 13 theme mutants 615:621 arg1 phenotypes 592:601 The biochemical phenotypes 576:601 The biochemical phenotypes of the PGM1 mutants 576:621 The biochemical phenotypes of the PGM1 mutants cluster into two groups: those with compromised catalysis and those with possible folding defects. 25288802 0 14 theme hereditary 108:117 arg1 deficiency 140:149 hereditary phosphoglucomutase 1 deficiency 108:149 hereditary phosphoglucomutase 1 deficiency 108:149 Compromised catalysis and potential folding defects in in vitro studies of missense mutants associated with hereditary phosphoglucomutase 1 deficiency. 25288802 8 15 theme serine 1263:1268 arg1 inability 1232:1240 the inability 1228:1240 the inability of a key active site serine to be phosphorylated, a prerequisite for catalysis 1228:1319 In the case of the G291R mutant, severely compromised activity is linked to the inability of a key active site serine to be phosphorylated, a prerequisite for catalysis. 25288802 3 16 theme in 484:485 arg1 characterization 505:520 the first in vitro biochemical characterization 474:520 the first in vitro biochemical characterization of 13 missense mutations involved in PGM1 deficiency 474:573 We present here the first in vitro biochemical characterization of 13 missense mutations involved in PGM1 deficiency. 25288802 2 17 theme multiple 291:298 arg1 intolerance 363:373 exercise intolerance 354:373 exercise intolerance 354:373 Affected patients show multiple disease phenotypes, including dilated cardiomyopathy, exercise intolerance, and hepatopathy, reflecting the central role of the enzyme in glucose metabolism. 25288802 2 17 theme multiple 291:298 arg1 hepatopathy 380:390 hepatopathy 380:390 hepatopathy 380:390 Affected patients show multiple disease phenotypes, including dilated cardiomyopathy, exercise intolerance, and hepatopathy, reflecting the central role of the enzyme in glucose metabolism. 25288802 2 17 theme multiple 291:298 arg1 phenotypes 308:317 multiple disease phenotypes 291:317 multiple disease phenotypes 291:317 Affected patients show multiple disease phenotypes, including dilated cardiomyopathy, exercise intolerance, and hepatopathy, reflecting the central role of the enzyme in glucose metabolism. 25288802 2 17 theme multiple 291:298 arg1 cardiomyopathy 338:351 dilated cardiomyopathy 330:351 dilated cardiomyopathy 330:351 Affected patients show multiple disease phenotypes, including dilated cardiomyopathy, exercise intolerance, and hepatopathy, reflecting the central role of the enzyme in glucose metabolism. 25288802 4 18 theme possible 696:703 arg1 defects 713:719 possible folding defects 696:719 possible folding defects 696:719 The biochemical phenotypes of the PGM1 mutants cluster into two groups: those with compromised catalysis and those with possible folding defects. 25288802 1 19 theme phosphoglucomutase 183:200 arg1 disorder 248:255 an inherited metabolic disorder 225:255 an inherited metabolic disorder in humans 225:265 Recent studies have identified phosphoglucomutase 1 (PGM1) deficiency as an inherited metabolic disorder in humans. 25288802 1 19 theme phosphoglucomutase 183:200 arg1 deficiency 211:220 phosphoglucomutase 1 (PGM1) deficiency 183:220 phosphoglucomutase 1 (PGM1) deficiency 183:220 Recent studies have identified phosphoglucomutase 1 (PGM1) deficiency as an inherited metabolic disorder in humans. 25288802 5 20 theme missense 776:783 arg1 mutants 785:791 certain missense mutants 768:791 certain missense mutants 768:791 Relative to the recombinant wild-type enzyme, certain missense mutants show greatly decreased expression of soluble protein and/or increased aggregation. 25288802 7 21 theme impaired 1133:1140 arg1 variants 1142:1149 the catalytically impaired variants 1115:1149 the catalytically impaired variants 1115:1149 Modest changes in protein conformation and flexibility are also apparent in some of the catalytically impaired variants. 25288802 3 22 theme PGM1 559:562 arg1 deficiency 564:573 PGM1 deficiency 559:573 PGM1 deficiency 559:573 We present here the first in vitro biochemical characterization of 13 missense mutations involved in PGM1 deficiency. 25288802 7 23 from some 1107:1110 arg1 apparent 1095:1102 apparent 1095:1102 apparent 1095:1102 Modest changes in protein conformation and flexibility are also apparent in some of the catalytically impaired variants. 25288802 5 24 theme certain 768:774 arg1 mutants 785:791 certain missense mutants 768:791 certain missense mutants 768:791 Relative to the recombinant wild-type enzyme, certain missense mutants show greatly decreased expression of soluble protein and/or increased aggregation. 25288802 6 25 theme <1.5 1011:1014 arg1 % 1015:1015 % 1015:1015 % 1015:1015 In contrast, other missense variants are well behaved in solution, but show dramatic reductions in enzyme activity, with kcat/Km often <1.5% of wild-type. 25288802 2 26 theme central 408:414 arg1 role 416:419 the central role 404:419 the central role of the enzyme in glucose metabolism 404:455 Affected patients show multiple disease phenotypes, including dilated cardiomyopathy, exercise intolerance, and hepatopathy, reflecting the central role of the enzyme in glucose metabolism. 25288802 5 27 theme increased 853:861 arg1 aggregation 863:873 increased aggregation 853:873 increased aggregation 853:873 Relative to the recombinant wild-type enzyme, certain missense mutants show greatly decreased expression of soluble protein and/or increased aggregation. 25288802 4 28 theme biochemical 580:590 arg1 phenotypes 592:601 The biochemical phenotypes 576:601 The biochemical phenotypes of the PGM1 mutants 576:621 The biochemical phenotypes of the PGM1 mutants cluster into two groups: those with compromised catalysis and those with possible folding defects. 25288802 8 29 theme active 1251:1256 arg1 serine 1263:1268 a key active site serine 1245:1268 a key active site serine 1245:1268 In the case of the G291R mutant, severely compromised activity is linked to the inability of a key active site serine to be phosphorylated, a prerequisite for catalysis. 25288802 2 30 theme dilated 330:336 arg1 cardiomyopathy 338:351 dilated cardiomyopathy 330:351 dilated cardiomyopathy 330:351 Affected patients show multiple disease phenotypes, including dilated cardiomyopathy, exercise intolerance, and hepatopathy, reflecting the central role of the enzyme in glucose metabolism. 25288802 8 31 theme G291R 1171:1175 arg1 mutant 1177:1182 the G291R mutant 1167:1182 the G291R mutant 1167:1182 In the case of the G291R mutant, severely compromised activity is linked to the inability of a key active site serine to be phosphorylated, a prerequisite for catalysis. 25288802 1 32 theme PGM1 205:208 arg1 disorder 248:255 an inherited metabolic disorder 225:255 an inherited metabolic disorder in humans 225:265 Recent studies have identified phosphoglucomutase 1 (PGM1) deficiency as an inherited metabolic disorder in humans. 25288802 1 32 theme PGM1 205:208 arg1 deficiency 211:220 phosphoglucomutase 1 (PGM1) deficiency 183:220 phosphoglucomutase 1 (PGM1) deficiency 183:220 Recent studies have identified phosphoglucomutase 1 (PGM1) deficiency as an inherited metabolic disorder in humans. 25288802 0 33 theme potential 26:34 arg1 defects 44:50 potential folding defects 26:50 potential folding defects 26:50 Compromised catalysis and potential folding defects in in vitro studies of missense mutants associated with hereditary phosphoglucomutase 1 deficiency. 25288802 9 34 theme in 1354:1355 arg1 studies 1362:1368 previous in vivo studies 1345:1368 previous in vivo studies 1345:1368 Our results complement previous in vivo studies, which suggest that both protein misfolding and catalytic impairment may play a role in PGM1 deficiency. 25288802 2 35 theme glucose 438:444 arg1 metabolism 446:455 glucose metabolism 438:455 glucose metabolism 438:455 Affected patients show multiple disease phenotypes, including dilated cardiomyopathy, exercise intolerance, and hepatopathy, reflecting the central role of the enzyme in glucose metabolism. 25288802 0 36 theme phosphoglucomutase 119:136 arg1 deficiency 140:149 hereditary phosphoglucomutase 1 deficiency 108:149 hereditary phosphoglucomutase 1 deficiency 108:149 Compromised catalysis and potential folding defects in in vitro studies of missense mutants associated with hereditary phosphoglucomutase 1 deficiency. 25288802 3 37 theme mutations 537:545 arg1 characterization 505:520 the first in vitro biochemical characterization 474:520 the first in vitro biochemical characterization of 13 missense mutations involved in PGM1 deficiency 474:573 We present here the first in vitro biochemical characterization of 13 missense mutations involved in PGM1 deficiency. 25288802 7 38 from changes 1038:1044 arg1 flexibility 1074:1084 flexibility 1074:1084 flexibility 1074:1084 Modest changes in protein conformation and flexibility are also apparent in some of the catalytically impaired variants. 25288802 7 38 from changes 1038:1044 arg1 conformation 1057:1068 protein conformation 1049:1068 protein conformation 1049:1068 Modest changes in protein conformation and flexibility are also apparent in some of the catalytically impaired variants. 25288802 5 39 theme recombinant 738:748 arg1 enzyme 760:765 the recombinant wild-type enzyme 734:765 the recombinant wild-type enzyme 734:765 Relative to the recombinant wild-type enzyme, certain missense mutants show greatly decreased expression of soluble protein and/or increased aggregation. 25288802 0 40 dep in 55:56 arg1 vitro 58:62 vitro 58:62 vitro 58:62 Compromised catalysis and potential folding defects in in vitro studies of missense mutants associated with hereditary phosphoglucomutase 1 deficiency. 25288802 8 41 theme site 1258:1261 arg1 serine 1263:1268 a key active site serine 1245:1268 a key active site serine 1245:1268 In the case of the G291R mutant, severely compromised activity is linked to the inability of a key active site serine to be phosphorylated, a prerequisite for catalysis. 25288802 2 42 theme enzyme 428:433 arg1 role 416:419 the central role 404:419 the central role of the enzyme in glucose metabolism 404:455 Affected patients show multiple disease phenotypes, including dilated cardiomyopathy, exercise intolerance, and hepatopathy, reflecting the central role of the enzyme in glucose metabolism. 25288802 0 43 theme folding 36:42 arg1 defects 44:50 potential folding defects 26:50 potential folding defects 26:50 Compromised catalysis and potential folding defects in in vitro studies of missense mutants associated with hereditary phosphoglucomutase 1 deficiency. 25288802 5 44 theme wild-type 750:758 arg1 enzyme 760:765 the recombinant wild-type enzyme 734:765 the recombinant wild-type enzyme 734:765 Relative to the recombinant wild-type enzyme, certain missense mutants show greatly decreased expression of soluble protein and/or increased aggregation. 25288802 5 45 theme aggregation 863:873 arg1 expression 816:825 greatly decreased expression 798:825 greatly decreased expression of soluble protein and/or increased aggregation 798:873 Relative to the recombinant wild-type enzyme, certain missense mutants show greatly decreased expression of soluble protein and/or increased aggregation. 25288802 9 46 theme catalytic 1418:1426 arg1 impairment 1428:1437 catalytic impairment 1418:1437 catalytic impairment 1418:1437 Our results complement previous in vivo studies, which suggest that both protein misfolding and catalytic impairment may play a role in PGM1 deficiency. 25288802 4 47 theme compromised 659:669 arg1 catalysis 671:679 compromised catalysis 659:679 compromised catalysis 659:679 The biochemical phenotypes of the PGM1 mutants cluster into two groups: those with compromised catalysis and those with possible folding defects. 25288802 0 48 theme in 55:56 arg1 studies 64:70 in vitro studies 55:70 in vitro studies of missense mutants associated with hereditary phosphoglucomutase 1 deficiency 55:149 Compromised catalysis and potential folding defects in in vitro studies of missense mutants associated with hereditary phosphoglucomutase 1 deficiency. 25288802 1 49 from disorder 248:255 arg1 humans 260:265 humans 260:265 humans 260:265 Recent studies have identified phosphoglucomutase 1 (PGM1) deficiency as an inherited metabolic disorder in humans. 25288802 6 50 theme missense 895:902 arg1 variants 904:911 other missense variants 889:911 other missense variants 889:911 In contrast, other missense variants are well behaved in solution, but show dramatic reductions in enzyme activity, with kcat/Km often <1.5% of wild-type. 25288802 8 51 attach linked 1218:1223 arg3 case 1159:1162 the case 1155:1162 the case of the G291R mutant 1155:1182 In the case of the G291R mutant, severely compromised activity is linked to the inability of a key active site serine to be phosphorylated, a prerequisite for catalysis. 25288802 8 51 attach linked 1218:1223 arg2 activity 1206:1213 severely compromised activity 1185:1213 severely compromised activity 1185:1213 In the case of the G291R mutant, severely compromised activity is linked to the inability of a key active site serine to be phosphorylated, a prerequisite for catalysis. 25288802 8 51 attach linked 1218:1223 arg1 inability 1232:1240 the inability 1228:1240 the inability of a key active site serine to be phosphorylated, a prerequisite for catalysis 1228:1319 In the case of the G291R mutant, severely compromised activity is linked to the inability of a key active site serine to be phosphorylated, a prerequisite for catalysis. 25288802 7 52 theme protein 1049:1055 arg1 conformation 1057:1068 protein conformation 1049:1068 protein conformation 1049:1068 Modest changes in protein conformation and flexibility are also apparent in some of the catalytically impaired variants. 25288802 5 53 theme protein 838:844 arg1 expression 816:825 greatly decreased expression 798:825 greatly decreased expression of soluble protein and/or increased aggregation 798:873 Relative to the recombinant wild-type enzyme, certain missense mutants show greatly decreased expression of soluble protein and/or increased aggregation. 25288802 6 54 theme enzyme 975:980 arg1 activity 982:989 enzyme activity 975:989 enzyme activity 975:989 In contrast, other missense variants are well behaved in solution, but show dramatic reductions in enzyme activity, with kcat/Km often <1.5% of wild-type. 25288802 6 55 theme other 889:893 arg1 variants 904:911 other missense variants 889:911 other missense variants 889:911 In contrast, other missense variants are well behaved in solution, but show dramatic reductions in enzyme activity, with kcat/Km often <1.5% of wild-type. 25288802 7 56 theme Modest 1031:1036 arg1 changes 1038:1044 Modest changes 1031:1044 Modest changes in protein conformation and flexibility 1031:1084 Modest changes in protein conformation and flexibility are also apparent in some of the catalytically impaired variants. 25288802 4 57 dep groups 640:645 arg1 those 685:689 those 685:689 those 685:689 The biochemical phenotypes of the PGM1 mutants cluster into two groups: those with compromised catalysis and those with possible folding defects. 25288802 4 57 dep groups 640:645 arg1 those 648:652 those 648:652 those 648:652 The biochemical phenotypes of the PGM1 mutants cluster into two groups: those with compromised catalysis and those with possible folding defects. 25288802 2 58 from role 416:419 arg1 metabolism 446:455 glucose metabolism 438:455 glucose metabolism 438:455 Affected patients show multiple disease phenotypes, including dilated cardiomyopathy, exercise intolerance, and hepatopathy, reflecting the central role of the enzyme in glucose metabolism. 25288802 2 59 theme exercise 354:361 arg1 intolerance 363:373 exercise intolerance 354:373 exercise intolerance 354:373 Affected patients show multiple disease phenotypes, including dilated cardiomyopathy, exercise intolerance, and hepatopathy, reflecting the central role of the enzyme in glucose metabolism. 25288802 1 60 theme inherited 228:236 arg1 disorder 248:255 an inherited metabolic disorder 225:255 an inherited metabolic disorder in humans 225:265 Recent studies have identified phosphoglucomutase 1 (PGM1) deficiency as an inherited metabolic disorder in humans. 25288802 1 60 theme inherited 228:236 arg1 deficiency 211:220 phosphoglucomutase 1 (PGM1) deficiency 183:220 phosphoglucomutase 1 (PGM1) deficiency 183:220 Recent studies have identified phosphoglucomutase 1 (PGM1) deficiency as an inherited metabolic disorder in humans. 25288802 8 61 theme compromised 1194:1204 arg1 activity 1206:1213 severely compromised activity 1185:1213 severely compromised activity 1185:1213 In the case of the G291R mutant, severely compromised activity is linked to the inability of a key active site serine to be phosphorylated, a prerequisite for catalysis. 25288802 2 62 theme Affected 268:275 arg1 patients 277:284 Affected patients 268:284 Affected patients 268:284 Affected patients show multiple disease phenotypes, including dilated cardiomyopathy, exercise intolerance, and hepatopathy, reflecting the central role of the enzyme in glucose metabolism. 25288802 3 63 theme biochemical 493:503 arg1 characterization 505:520 the first in vitro biochemical characterization 474:520 the first in vitro biochemical characterization of 13 missense mutations involved in PGM1 deficiency 474:573 We present here the first in vitro biochemical characterization of 13 missense mutations involved in PGM1 deficiency. 25288802 1 64 theme metabolic 238:246 arg1 disorder 248:255 an inherited metabolic disorder 225:255 an inherited metabolic disorder in humans 225:265 Recent studies have identified phosphoglucomutase 1 (PGM1) deficiency as an inherited metabolic disorder in humans. 25288802 1 64 theme metabolic 238:246 arg1 deficiency 211:220 phosphoglucomutase 1 (PGM1) deficiency 183:220 phosphoglucomutase 1 (PGM1) deficiency 183:220 Recent studies have identified phosphoglucomutase 1 (PGM1) deficiency as an inherited metabolic disorder in humans. 25288802 7 65 from apparent 1095:1102 arg1 variants 1142:1149 the catalytically impaired variants 1115:1149 the catalytically impaired variants 1115:1149 Modest changes in protein conformation and flexibility are also apparent in some of the catalytically impaired variants. 25288802 7 65 from apparent 1095:1102 arg1 some 1107:1110 some 1107:1110 some 1107:1110 Modest changes in protein conformation and flexibility are also apparent in some of the catalytically impaired variants. 25288802 3 66 theme first 478:482 arg1 characterization 505:520 the first in vitro biochemical characterization 474:520 the first in vitro biochemical characterization of 13 missense mutations involved in PGM1 deficiency 474:573 We present here the first in vitro biochemical characterization of 13 missense mutations involved in PGM1 deficiency. 25288802 1 67 theme Recent 152:157 arg1 studies 159:165 Recent studies 152:165 Recent studies 152:165 Recent studies have identified phosphoglucomutase 1 (PGM1) deficiency as an inherited metabolic disorder in humans. 25288802 8 68 theme key 1247:1249 arg1 serine 1263:1268 a key active site serine 1245:1268 a key active site serine 1245:1268 In the case of the G291R mutant, severely compromised activity is linked to the inability of a key active site serine to be phosphorylated, a prerequisite for catalysis. 25288802 5 69 theme soluble 830:836 arg1 protein 838:844 soluble protein 830:844 soluble protein 830:844 Relative to the recombinant wild-type enzyme, certain missense mutants show greatly decreased expression of soluble protein and/or increased aggregation. 25288802 3 70 dep in 484:485 arg1 vitro 487:491 vitro 487:491 vitro 487:491 We present here the first in vitro biochemical characterization of 13 missense mutations involved in PGM1 deficiency. 25288802 4 71 theme folding 705:711 arg1 defects 713:719 possible folding defects 696:719 possible folding defects 696:719 The biochemical phenotypes of the PGM1 mutants cluster into two groups: those with compromised catalysis and those with possible folding defects. 25288802 6 72 from reductions 961:970 arg1 activity 982:989 enzyme activity 975:989 enzyme activity 975:989 In contrast, other missense variants are well behaved in solution, but show dramatic reductions in enzyme activity, with kcat/Km often <1.5% of wild-type. 25288802 8 73 theme mutant 1177:1182 arg1 case 1159:1162 the case 1155:1162 the case of the G291R mutant 1155:1182 In the case of the G291R mutant, severely compromised activity is linked to the inability of a key active site serine to be phosphorylated, a prerequisite for catalysis. 28073289 3 0 theme CCR5-tropic 645:655 arg1 virus 584:588 The T/F virus 576:588 The T/F virus 576:588 The T/F virus was classified as subtype CRF07_BC and predicted to be CCR5-tropic virus. 28073289 3 0 theme CCR5-tropic 645:655 arg1 virus 657:661 CCR5-tropic virus 645:661 CCR5-tropic virus 645:661 The T/F virus was classified as subtype CRF07_BC and predicted to be CCR5-tropic virus. 28073289 4 1 theme consensus 782:790 arg1 HSX.CON 802:808 HSX.CON 802:808 HSX.CON 802:808 The variable region (V1, V2, and V4 loop) of IDU.CON showed length variation compared with the heterosexual T/F virus consensus sequence (HSX.CON) and homosexual T/F virus consensus sequence (MSM.CON). 28073289 4 1 theme consensus 782:790 arg1 sequence 792:799 the heterosexual T/F virus consensus sequence 755:799 the heterosexual T/F virus consensus sequence (HSX.CON) 755:809 The variable region (V1, V2, and V4 loop) of IDU.CON showed length variation compared with the heterosexual T/F virus consensus sequence (HSX.CON) and homosexual T/F virus consensus sequence (MSM.CON). 28073289 6 2 dep make-up 1061:1067 arg1 the 1049:1051 the 1049:1051 the 1049:1051 Characterization of T/F virus from IDUs highlights the genetic make-up and complexity of virus near the moment of transmission or in early infection preceding systemic dissemination and is important toward the development of an effective HIV-1 preventive methods, including vaccines. 28073289 2 3 theme single 384:389 arg1 sequencing 398:407 single genome sequencing 384:407 single genome sequencing (SGS) 384:413 We investigated a total of 749 sequences of full-length gp160 gene obtained by single genome sequencing (SGS) from 22 HIV-1 early infected IDUs in Xinjiang province, northwest China, and generated a transmitted and founder virus (T/F virus) consensus sequence (IDU.CON). 28073289 2 3 theme single 384:389 arg1 SGS 410:412 SGS 410:412 SGS 410:412 We investigated a total of 749 sequences of full-length gp160 gene obtained by single genome sequencing (SGS) from 22 HIV-1 early infected IDUs in Xinjiang province, northwest China, and generated a transmitted and founder virus (T/F virus) consensus sequence (IDU.CON). 28073289 4 4 theme virus 776:780 arg1 HSX.CON 802:808 HSX.CON 802:808 HSX.CON 802:808 The variable region (V1, V2, and V4 loop) of IDU.CON showed length variation compared with the heterosexual T/F virus consensus sequence (HSX.CON) and homosexual T/F virus consensus sequence (MSM.CON). 28073289 4 4 theme virus 776:780 arg1 sequence 792:799 the heterosexual T/F virus consensus sequence 755:799 the heterosexual T/F virus consensus sequence (HSX.CON) 755:809 The variable region (V1, V2, and V4 loop) of IDU.CON showed length variation compared with the heterosexual T/F virus consensus sequence (HSX.CON) and homosexual T/F virus consensus sequence (MSM.CON). 28073289 1 5 theme intravenous 160:170 arg1 IDUs 184:187 IDUs 184:187 IDUs 184:187 HIV-1 transmission in intravenous drug users (IDUs) has been characterized by high genetic multiplicity and suggests a greater challenge for HIV-1 infection blocking. 28073289 1 5 theme intravenous 160:170 arg1 users 177:181 intravenous drug users 160:181 intravenous drug users (IDUs) 160:188 HIV-1 transmission in intravenous drug users (IDUs) has been characterized by high genetic multiplicity and suggests a greater challenge for HIV-1 infection blocking. 28073289 4 6 theme virus 830:834 arg1 MSM.CON 856:862 MSM.CON 856:862 MSM.CON 856:862 The variable region (V1, V2, and V4 loop) of IDU.CON showed length variation compared with the heterosexual T/F virus consensus sequence (HSX.CON) and homosexual T/F virus consensus sequence (MSM.CON). 28073289 4 6 theme virus 830:834 arg1 sequence 846:853 homosexual T/F virus consensus sequence 815:853 homosexual T/F virus consensus sequence (MSM.CON) 815:863 The variable region (V1, V2, and V4 loop) of IDU.CON showed length variation compared with the heterosexual T/F virus consensus sequence (HSX.CON) and homosexual T/F virus consensus sequence (MSM.CON). 28073289 0 7 theme Drug 107:110 arg1 Users 112:116 Intravenous Drug Users 95:116 Intravenous Drug Users in Xinjiang, China 95:135 Generation and Characterization of HIV-1 Transmitted and Founder Virus Consensus Sequence from Intravenous Drug Users in Xinjiang, China. 28073289 2 8 theme consensus 546:554 arg1 sequence 556:563 a transmitted and founder virus (T/F virus) consensus sequence 502:563 a transmitted and founder virus (T/F virus) consensus sequence (IDU.CON) 502:573 We investigated a total of 749 sequences of full-length gp160 gene obtained by single genome sequencing (SGS) from 22 HIV-1 early infected IDUs in Xinjiang province, northwest China, and generated a transmitted and founder virus (T/F virus) consensus sequence (IDU.CON). 28073289 2 8 theme consensus 546:554 arg1 IDU.CON 566:572 IDU.CON 566:572 IDU.CON 566:572 We investigated a total of 749 sequences of full-length gp160 gene obtained by single genome sequencing (SGS) from 22 HIV-1 early infected IDUs in Xinjiang province, northwest China, and generated a transmitted and founder virus (T/F virus) consensus sequence (IDU.CON). 28073289 6 9 theme transmission 1112:1123 arg1 moment 1102:1107 the moment 1098:1107 the moment of transmission 1098:1123 Characterization of T/F virus from IDUs highlights the genetic make-up and complexity of virus near the moment of transmission or in early infection preceding systemic dissemination and is important toward the development of an effective HIV-1 preventive methods, including vaccines. 28073289 0 10 theme Intravenous 95:105 arg1 Users 112:116 Intravenous Drug Users 95:116 Intravenous Drug Users in Xinjiang, China 95:135 Generation and Characterization of HIV-1 Transmitted and Founder Virus Consensus Sequence from Intravenous Drug Users in Xinjiang, China. 28073289 1 11 theme greater 257:263 arg1 challenge 265:273 a greater challenge 255:273 a greater challenge for HIV-1 infection blocking 255:302 HIV-1 transmission in intravenous drug users (IDUs) has been characterized by high genetic multiplicity and suggests a greater challenge for HIV-1 infection blocking. 28073289 6 12 theme systemic 1157:1164 arg1 dissemination 1166:1178 systemic dissemination 1157:1178 systemic dissemination 1157:1178 Characterization of T/F virus from IDUs highlights the genetic make-up and complexity of virus near the moment of transmission or in early infection preceding systemic dissemination and is important toward the development of an effective HIV-1 preventive methods, including vaccines. 28073289 1 13 from transmission 144:155 arg1 IDUs 184:187 IDUs 184:187 IDUs 184:187 HIV-1 transmission in intravenous drug users (IDUs) has been characterized by high genetic multiplicity and suggests a greater challenge for HIV-1 infection blocking. 28073289 1 13 from transmission 144:155 arg1 users 177:181 intravenous drug users 160:181 intravenous drug users (IDUs) 160:188 HIV-1 transmission in intravenous drug users (IDUs) has been characterized by high genetic multiplicity and suggests a greater challenge for HIV-1 infection blocking. 28073289 4 14 theme V4 697:698 arg1 loop 700:703 V4 loop 697:703 V4 loop 697:703 The variable region (V1, V2, and V4 loop) of IDU.CON showed length variation compared with the heterosexual T/F virus consensus sequence (HSX.CON) and homosexual T/F virus consensus sequence (MSM.CON). 28073289 6 15 from make-up 1061:1067 arg1 infection 1137:1145 early infection 1131:1145 early infection preceding systemic dissemination 1131:1178 Characterization of T/F virus from IDUs highlights the genetic make-up and complexity of virus near the moment of transmission or in early infection preceding systemic dissemination and is important toward the development of an effective HIV-1 preventive methods, including vaccines. 28073289 1 16 theme drug 172:175 arg1 IDUs 184:187 IDUs 184:187 IDUs 184:187 HIV-1 transmission in intravenous drug users (IDUs) has been characterized by high genetic multiplicity and suggests a greater challenge for HIV-1 infection blocking. 28073289 1 16 theme drug 172:175 arg1 users 177:181 intravenous drug users 160:181 intravenous drug users (IDUs) 160:188 HIV-1 transmission in intravenous drug users (IDUs) has been characterized by high genetic multiplicity and suggests a greater challenge for HIV-1 infection blocking. 28073289 6 17 theme methods 1253:1259 arg1 development 1208:1218 the development 1204:1218 the development of an effective HIV-1 preventive methods, including vaccines 1204:1279 Characterization of T/F virus from IDUs highlights the genetic make-up and complexity of virus near the moment of transmission or in early infection preceding systemic dissemination and is important toward the development of an effective HIV-1 preventive methods, including vaccines. 28073289 6 18 theme T/F 1018:1020 arg1 virus 1022:1026 T/F virus 1018:1026 T/F virus from IDUs 1018:1036 Characterization of T/F virus from IDUs highlights the genetic make-up and complexity of virus near the moment of transmission or in early infection preceding systemic dissemination and is important toward the development of an effective HIV-1 preventive methods, including vaccines. 28073289 5 19 theme 26 N-linked 877:887 arg1 sites 903:907 26 N-linked glycosylation sites 877:907 26 N-linked glycosylation sites 877:907 A total of 26 N-linked glycosylation sites were discovered in the IDU.CON sequence, which is less than that of MSM.CON and HSX.CON. 28073289 2 20 theme HIV-1 423:427 arg1 IDUs 444:447 22 HIV-1 early infected IDUs 420:447 22 HIV-1 early infected IDUs in Xinjiang province, northwest China 420:485 We investigated a total of 749 sequences of full-length gp160 gene obtained by single genome sequencing (SGS) from 22 HIV-1 early infected IDUs in Xinjiang province, northwest China, and generated a transmitted and founder virus (T/F virus) consensus sequence (IDU.CON). 28073289 2 21 from IDUs 444:447 arg1 China 481:485 China 481:485 China 481:485 We investigated a total of 749 sequences of full-length gp160 gene obtained by single genome sequencing (SGS) from 22 HIV-1 early infected IDUs in Xinjiang province, northwest China, and generated a transmitted and founder virus (T/F virus) consensus sequence (IDU.CON). 28073289 4 22 theme T/F 772:774 arg1 HSX.CON 802:808 HSX.CON 802:808 HSX.CON 802:808 The variable region (V1, V2, and V4 loop) of IDU.CON showed length variation compared with the heterosexual T/F virus consensus sequence (HSX.CON) and homosexual T/F virus consensus sequence (MSM.CON). 28073289 4 22 theme T/F 772:774 arg1 sequence 792:799 the heterosexual T/F virus consensus sequence 755:799 the heterosexual T/F virus consensus sequence (HSX.CON) 755:809 The variable region (V1, V2, and V4 loop) of IDU.CON showed length variation compared with the heterosexual T/F virus consensus sequence (HSX.CON) and homosexual T/F virus consensus sequence (MSM.CON). 28073289 6 23 theme genetic 1053:1059 arg1 make-up 1061:1067 genetic make-up 1053:1067 genetic make-up 1053:1067 Characterization of T/F virus from IDUs highlights the genetic make-up and complexity of virus near the moment of transmission or in early infection preceding systemic dissemination and is important toward the development of an effective HIV-1 preventive methods, including vaccines. 28073289 6 24 from complexity 1073:1082 arg1 infection 1137:1145 early infection 1131:1145 early infection preceding systemic dissemination 1131:1178 Characterization of T/F virus from IDUs highlights the genetic make-up and complexity of virus near the moment of transmission or in early infection preceding systemic dissemination and is important toward the development of an effective HIV-1 preventive methods, including vaccines. 28073289 6 25 theme effective 1226:1234 arg1 methods 1253:1259 an effective HIV-1 preventive methods 1223:1259 an effective HIV-1 preventive methods 1223:1259 Characterization of T/F virus from IDUs highlights the genetic make-up and complexity of virus near the moment of transmission or in early infection preceding systemic dissemination and is important toward the development of an effective HIV-1 preventive methods, including vaccines. 28073289 6 25 theme effective 1226:1234 arg1 vaccines 1272:1279 vaccines 1272:1279 vaccines 1272:1279 Characterization of T/F virus from IDUs highlights the genetic make-up and complexity of virus near the moment of transmission or in early infection preceding systemic dissemination and is important toward the development of an effective HIV-1 preventive methods, including vaccines. 28073289 6 26 theme preventive 1242:1251 arg1 methods 1253:1259 an effective HIV-1 preventive methods 1223:1259 an effective HIV-1 preventive methods 1223:1259 Characterization of T/F virus from IDUs highlights the genetic make-up and complexity of virus near the moment of transmission or in early infection preceding systemic dissemination and is important toward the development of an effective HIV-1 preventive methods, including vaccines. 28073289 6 26 theme preventive 1242:1251 arg1 vaccines 1272:1279 vaccines 1272:1279 vaccines 1272:1279 Characterization of T/F virus from IDUs highlights the genetic make-up and complexity of virus near the moment of transmission or in early infection preceding systemic dissemination and is important toward the development of an effective HIV-1 preventive methods, including vaccines. 28073289 4 27 theme heterosexual 759:770 arg1 HSX.CON 802:808 HSX.CON 802:808 HSX.CON 802:808 The variable region (V1, V2, and V4 loop) of IDU.CON showed length variation compared with the heterosexual T/F virus consensus sequence (HSX.CON) and homosexual T/F virus consensus sequence (MSM.CON). 28073289 4 27 theme heterosexual 759:770 arg1 sequence 792:799 the heterosexual T/F virus consensus sequence 755:799 the heterosexual T/F virus consensus sequence (HSX.CON) 755:809 The variable region (V1, V2, and V4 loop) of IDU.CON showed length variation compared with the heterosexual T/F virus consensus sequence (HSX.CON) and homosexual T/F virus consensus sequence (MSM.CON). 28073289 0 28 dep Sequence 81:88 arg1 Founder 57:63 Founder 57:63 Founder 57:63 Generation and Characterization of HIV-1 Transmitted and Founder Virus Consensus Sequence from Intravenous Drug Users in Xinjiang, China. 28073289 6 29 theme HIV-1 1236:1240 arg1 methods 1253:1259 an effective HIV-1 preventive methods 1223:1259 an effective HIV-1 preventive methods 1223:1259 Characterization of T/F virus from IDUs highlights the genetic make-up and complexity of virus near the moment of transmission or in early infection preceding systemic dissemination and is important toward the development of an effective HIV-1 preventive methods, including vaccines. 28073289 6 29 theme HIV-1 1236:1240 arg1 vaccines 1272:1279 vaccines 1272:1279 vaccines 1272:1279 Characterization of T/F virus from IDUs highlights the genetic make-up and complexity of virus near the moment of transmission or in early infection preceding systemic dissemination and is important toward the development of an effective HIV-1 preventive methods, including vaccines. 28073289 2 30 theme gene 367:370 arg1 sequences 336:344 749 sequences 332:344 749 sequences of full-length gp160 gene obtained by single genome sequencing (SGS) from 22 HIV-1 early infected IDUs in Xinjiang province, northwest China 332:485 We investigated a total of 749 sequences of full-length gp160 gene obtained by single genome sequencing (SGS) from 22 HIV-1 early infected IDUs in Xinjiang province, northwest China, and generated a transmitted and founder virus (T/F virus) consensus sequence (IDU.CON). 28073289 2 31 theme founder 520:526 arg1 sequence 556:563 a transmitted and founder virus (T/F virus) consensus sequence 502:563 a transmitted and founder virus (T/F virus) consensus sequence (IDU.CON) 502:573 We investigated a total of 749 sequences of full-length gp160 gene obtained by single genome sequencing (SGS) from 22 HIV-1 early infected IDUs in Xinjiang province, northwest China, and generated a transmitted and founder virus (T/F virus) consensus sequence (IDU.CON). 28073289 2 31 theme founder 520:526 arg1 IDU.CON 566:572 IDU.CON 566:572 IDU.CON 566:572 We investigated a total of 749 sequences of full-length gp160 gene obtained by single genome sequencing (SGS) from 22 HIV-1 early infected IDUs in Xinjiang province, northwest China, and generated a transmitted and founder virus (T/F virus) consensus sequence (IDU.CON). 28073289 6 32 from IDUs 1033:1036 arg1 Characterization 998:1013 Characterization 998:1013 Characterization of T/F virus from IDUs 998:1036 Characterization of T/F virus from IDUs highlights the genetic make-up and complexity of virus near the moment of transmission or in early infection preceding systemic dissemination and is important toward the development of an effective HIV-1 preventive methods, including vaccines. 28073289 6 32 from IDUs 1033:1036 arg1 virus 1022:1026 T/F virus 1018:1026 T/F virus from IDUs 1018:1036 Characterization of T/F virus from IDUs highlights the genetic make-up and complexity of virus near the moment of transmission or in early infection preceding systemic dissemination and is important toward the development of an effective HIV-1 preventive methods, including vaccines. 28073289 1 33 theme HIV-1 279:283 arg1 infection 285:293 HIV-1 infection blocking 279:302 HIV-1 infection blocking 279:302 HIV-1 transmission in intravenous drug users (IDUs) has been characterized by high genetic multiplicity and suggests a greater challenge for HIV-1 infection blocking. 28073289 4 34 theme T/F 826:828 arg1 MSM.CON 856:862 MSM.CON 856:862 MSM.CON 856:862 The variable region (V1, V2, and V4 loop) of IDU.CON showed length variation compared with the heterosexual T/F virus consensus sequence (HSX.CON) and homosexual T/F virus consensus sequence (MSM.CON). 28073289 4 34 theme T/F 826:828 arg1 sequence 846:853 homosexual T/F virus consensus sequence 815:853 homosexual T/F virus consensus sequence (MSM.CON) 815:863 The variable region (V1, V2, and V4 loop) of IDU.CON showed length variation compared with the heterosexual T/F virus consensus sequence (HSX.CON) and homosexual T/F virus consensus sequence (MSM.CON). 28073289 5 35 gly glycosylation 889:901 arg2 sites 903:907 26 N-linked glycosylation sites 877:907 26 N-linked glycosylation sites 877:907 A total of 26 N-linked glycosylation sites were discovered in the IDU.CON sequence, which is less than that of MSM.CON and HSX.CON. 28073289 2 36 theme sequences 336:344 arg1 total 323:327 a total 321:327 a total of 749 sequences of full-length gp160 gene obtained by single genome sequencing (SGS) from 22 HIV-1 early infected IDUs in Xinjiang province, northwest China 321:485 We investigated a total of 749 sequences of full-length gp160 gene obtained by single genome sequencing (SGS) from 22 HIV-1 early infected IDUs in Xinjiang province, northwest China, and generated a transmitted and founder virus (T/F virus) consensus sequence (IDU.CON). 28073289 1 37 theme HIV-1 138:142 arg1 transmission 144:155 HIV-1 transmission 138:155 HIV-1 transmission in intravenous drug users (IDUs) 138:188 HIV-1 transmission in intravenous drug users (IDUs) has been characterized by high genetic multiplicity and suggests a greater challenge for HIV-1 infection blocking. 28073289 2 38 theme transmitted 504:514 arg1 sequence 556:563 a transmitted and founder virus (T/F virus) consensus sequence 502:563 a transmitted and founder virus (T/F virus) consensus sequence (IDU.CON) 502:573 We investigated a total of 749 sequences of full-length gp160 gene obtained by single genome sequencing (SGS) from 22 HIV-1 early infected IDUs in Xinjiang province, northwest China, and generated a transmitted and founder virus (T/F virus) consensus sequence (IDU.CON). 28073289 2 38 theme transmitted 504:514 arg1 IDU.CON 566:572 IDU.CON 566:572 IDU.CON 566:572 We investigated a total of 749 sequences of full-length gp160 gene obtained by single genome sequencing (SGS) from 22 HIV-1 early infected IDUs in Xinjiang province, northwest China, and generated a transmitted and founder virus (T/F virus) consensus sequence (IDU.CON). 28073289 4 39 theme length 724:729 arg1 variation 731:739 length variation 724:739 length variation 724:739 The variable region (V1, V2, and V4 loop) of IDU.CON showed length variation compared with the heterosexual T/F virus consensus sequence (HSX.CON) and homosexual T/F virus consensus sequence (MSM.CON). 28073289 0 40 theme HIV-1 35:39 arg1 Characterization 15:30 Characterization 15:30 Characterization 15:30 Generation and Characterization of HIV-1 Transmitted and Founder Virus Consensus Sequence from Intravenous Drug Users in Xinjiang, China. 28073289 0 40 theme HIV-1 35:39 arg1 Generation 0:9 Generation 0:9 Generation 0:9 Generation and Characterization of HIV-1 Transmitted and Founder Virus Consensus Sequence from Intravenous Drug Users in Xinjiang, China. 28073289 1 41 theme blocking 295:302 arg1 infection 285:293 HIV-1 infection blocking 279:302 HIV-1 infection blocking 279:302 HIV-1 transmission in intravenous drug users (IDUs) has been characterized by high genetic multiplicity and suggests a greater challenge for HIV-1 infection blocking. 28073289 4 42 theme consensus 836:844 arg1 MSM.CON 856:862 MSM.CON 856:862 MSM.CON 856:862 The variable region (V1, V2, and V4 loop) of IDU.CON showed length variation compared with the heterosexual T/F virus consensus sequence (HSX.CON) and homosexual T/F virus consensus sequence (MSM.CON). 28073289 4 42 theme consensus 836:844 arg1 sequence 846:853 homosexual T/F virus consensus sequence 815:853 homosexual T/F virus consensus sequence (MSM.CON) 815:863 The variable region (V1, V2, and V4 loop) of IDU.CON showed length variation compared with the heterosexual T/F virus consensus sequence (HSX.CON) and homosexual T/F virus consensus sequence (MSM.CON). 28073289 3 43 theme T/F 580:582 arg1 CRF07_BC 616:623 subtype CRF07_BC 608:623 subtype CRF07_BC 608:623 The T/F virus was classified as subtype CRF07_BC and predicted to be CCR5-tropic virus. 28073289 3 43 theme T/F 580:582 arg1 virus 584:588 The T/F virus 576:588 The T/F virus 576:588 The T/F virus was classified as subtype CRF07_BC and predicted to be CCR5-tropic virus. 28073289 3 43 theme T/F 580:582 arg1 virus 657:661 CCR5-tropic virus 645:661 CCR5-tropic virus 645:661 The T/F virus was classified as subtype CRF07_BC and predicted to be CCR5-tropic virus. 28073289 2 44 theme genome 391:396 arg1 sequencing 398:407 single genome sequencing 384:407 single genome sequencing (SGS) 384:413 We investigated a total of 749 sequences of full-length gp160 gene obtained by single genome sequencing (SGS) from 22 HIV-1 early infected IDUs in Xinjiang province, northwest China, and generated a transmitted and founder virus (T/F virus) consensus sequence (IDU.CON). 28073289 2 44 theme genome 391:396 arg1 SGS 410:412 SGS 410:412 SGS 410:412 We investigated a total of 749 sequences of full-length gp160 gene obtained by single genome sequencing (SGS) from 22 HIV-1 early infected IDUs in Xinjiang province, northwest China, and generated a transmitted and founder virus (T/F virus) consensus sequence (IDU.CON). 28073289 2 45 theme infected 435:442 arg1 IDUs 444:447 22 HIV-1 early infected IDUs 420:447 22 HIV-1 early infected IDUs in Xinjiang province, northwest China 420:485 We investigated a total of 749 sequences of full-length gp160 gene obtained by single genome sequencing (SGS) from 22 HIV-1 early infected IDUs in Xinjiang province, northwest China, and generated a transmitted and founder virus (T/F virus) consensus sequence (IDU.CON). 28073289 2 46 theme virus 539:543 arg1 sequence 556:563 a transmitted and founder virus (T/F virus) consensus sequence 502:563 a transmitted and founder virus (T/F virus) consensus sequence (IDU.CON) 502:573 We investigated a total of 749 sequences of full-length gp160 gene obtained by single genome sequencing (SGS) from 22 HIV-1 early infected IDUs in Xinjiang province, northwest China, and generated a transmitted and founder virus (T/F virus) consensus sequence (IDU.CON). 28073289 2 46 theme virus 539:543 arg1 IDU.CON 566:572 IDU.CON 566:572 IDU.CON 566:572 We investigated a total of 749 sequences of full-length gp160 gene obtained by single genome sequencing (SGS) from 22 HIV-1 early infected IDUs in Xinjiang province, northwest China, and generated a transmitted and founder virus (T/F virus) consensus sequence (IDU.CON). 28073289 5 47 theme IDU.CON 932:938 arg1 less 959:962 less 959:962 less 959:962 A total of 26 N-linked glycosylation sites were discovered in the IDU.CON sequence, which is less than that of MSM.CON and HSX.CON. 28073289 5 47 theme IDU.CON 932:938 arg1 sequence 940:947 the IDU.CON sequence 928:947 the IDU.CON sequence 928:947 A total of 26 N-linked glycosylation sites were discovered in the IDU.CON sequence, which is less than that of MSM.CON and HSX.CON. 28073289 6 48 theme early 1131:1135 arg1 infection 1137:1145 early infection 1131:1145 early infection preceding systemic dissemination 1131:1178 Characterization of T/F virus from IDUs highlights the genetic make-up and complexity of virus near the moment of transmission or in early infection preceding systemic dissemination and is important toward the development of an effective HIV-1 preventive methods, including vaccines. 28073289 2 49 theme early 429:433 arg1 IDUs 444:447 22 HIV-1 early infected IDUs 420:447 22 HIV-1 early infected IDUs in Xinjiang province, northwest China 420:485 We investigated a total of 749 sequences of full-length gp160 gene obtained by single genome sequencing (SGS) from 22 HIV-1 early infected IDUs in Xinjiang province, northwest China, and generated a transmitted and founder virus (T/F virus) consensus sequence (IDU.CON). 28073289 2 50 theme T/F 535:537 arg1 sequence 556:563 a transmitted and founder virus (T/F virus) consensus sequence 502:563 a transmitted and founder virus (T/F virus) consensus sequence (IDU.CON) 502:573 We investigated a total of 749 sequences of full-length gp160 gene obtained by single genome sequencing (SGS) from 22 HIV-1 early infected IDUs in Xinjiang province, northwest China, and generated a transmitted and founder virus (T/F virus) consensus sequence (IDU.CON). 28073289 2 50 theme T/F 535:537 arg1 IDU.CON 566:572 IDU.CON 566:572 IDU.CON 566:572 We investigated a total of 749 sequences of full-length gp160 gene obtained by single genome sequencing (SGS) from 22 HIV-1 early infected IDUs in Xinjiang province, northwest China, and generated a transmitted and founder virus (T/F virus) consensus sequence (IDU.CON). 28073289 6 51 theme virus 1022:1026 arg1 Characterization 998:1013 Characterization 998:1013 Characterization of T/F virus from IDUs 998:1036 Characterization of T/F virus from IDUs highlights the genetic make-up and complexity of virus near the moment of transmission or in early infection preceding systemic dissemination and is important toward the development of an effective HIV-1 preventive methods, including vaccines. 28073289 4 52 theme homosexual 815:824 arg1 MSM.CON 856:862 MSM.CON 856:862 MSM.CON 856:862 The variable region (V1, V2, and V4 loop) of IDU.CON showed length variation compared with the heterosexual T/F virus consensus sequence (HSX.CON) and homosexual T/F virus consensus sequence (MSM.CON). 28073289 4 52 theme homosexual 815:824 arg1 sequence 846:853 homosexual T/F virus consensus sequence 815:853 homosexual T/F virus consensus sequence (MSM.CON) 815:863 The variable region (V1, V2, and V4 loop) of IDU.CON showed length variation compared with the heterosexual T/F virus consensus sequence (HSX.CON) and homosexual T/F virus consensus sequence (MSM.CON). 28073289 0 53 from Users 112:116 arg1 China 131:135 China 131:135 China 131:135 Generation and Characterization of HIV-1 Transmitted and Founder Virus Consensus Sequence from Intravenous Drug Users in Xinjiang, China. 28073289 5 54 theme glycosylation 889:901 arg1 sites 903:907 26 N-linked glycosylation sites 877:907 26 N-linked glycosylation sites 877:907 A total of 26 N-linked glycosylation sites were discovered in the IDU.CON sequence, which is less than that of MSM.CON and HSX.CON. 28073289 4 55 theme variable 668:675 arg1 region 677:682 The variable region 664:682 The variable region (V1, V2, and V4 loop) of IDU.CON 664:715 The variable region (V1, V2, and V4 loop) of IDU.CON showed length variation compared with the heterosexual T/F virus consensus sequence (HSX.CON) and homosexual T/F virus consensus sequence (MSM.CON). 28073289 2 56 theme virus 528:532 arg1 sequence 556:563 a transmitted and founder virus (T/F virus) consensus sequence 502:563 a transmitted and founder virus (T/F virus) consensus sequence (IDU.CON) 502:573 We investigated a total of 749 sequences of full-length gp160 gene obtained by single genome sequencing (SGS) from 22 HIV-1 early infected IDUs in Xinjiang province, northwest China, and generated a transmitted and founder virus (T/F virus) consensus sequence (IDU.CON). 28073289 2 56 theme virus 528:532 arg1 IDU.CON 566:572 IDU.CON 566:572 IDU.CON 566:572 We investigated a total of 749 sequences of full-length gp160 gene obtained by single genome sequencing (SGS) from 22 HIV-1 early infected IDUs in Xinjiang province, northwest China, and generated a transmitted and founder virus (T/F virus) consensus sequence (IDU.CON). 28073289 5 57 theme sites 903:907 arg1 total 868:872 A total 866:872 A total of 26 N-linked glycosylation sites 866:907 A total of 26 N-linked glycosylation sites were discovered in the IDU.CON sequence, which is less than that of MSM.CON and HSX.CON. 28073289 4 58 dep region 677:682 arg1 V1 685:686 V1 685:686 V1 685:686 The variable region (V1, V2, and V4 loop) of IDU.CON showed length variation compared with the heterosexual T/F virus consensus sequence (HSX.CON) and homosexual T/F virus consensus sequence (MSM.CON). 28073289 4 58 dep region 677:682 arg1 loop 700:703 V4 loop 697:703 V4 loop 697:703 The variable region (V1, V2, and V4 loop) of IDU.CON showed length variation compared with the heterosexual T/F virus consensus sequence (HSX.CON) and homosexual T/F virus consensus sequence (MSM.CON). 28073289 4 58 dep region 677:682 arg1 V2 689:690 V2 689:690 V2 689:690 The variable region (V1, V2, and V4 loop) of IDU.CON showed length variation compared with the heterosexual T/F virus consensus sequence (HSX.CON) and homosexual T/F virus consensus sequence (MSM.CON). 28073289 1 59 theme high 216:219 arg1 multiplicity 229:240 high genetic multiplicity 216:240 high genetic multiplicity 216:240 HIV-1 transmission in intravenous drug users (IDUs) has been characterized by high genetic multiplicity and suggests a greater challenge for HIV-1 infection blocking. 28073289 0 60 theme Consensus 71:79 arg1 Sequence 81:88 and Founder Virus Consensus Sequence 53:88 Sequence 81:88 Generation and Characterization of HIV-1 Transmitted and Founder Virus Consensus Sequence from Intravenous Drug Users in Xinjiang, China. 28073289 3 61 theme subtype 608:614 arg1 CRF07_BC 616:623 subtype CRF07_BC 608:623 subtype CRF07_BC 608:623 The T/F virus was classified as subtype CRF07_BC and predicted to be CCR5-tropic virus. 28073289 3 61 theme subtype 608:614 arg1 virus 584:588 The T/F virus 576:588 The T/F virus 576:588 The T/F virus was classified as subtype CRF07_BC and predicted to be CCR5-tropic virus. 28073289 4 62 theme IDU.CON 709:715 arg1 region 677:682 The variable region 664:682 The variable region (V1, V2, and V4 loop) of IDU.CON 664:715 The variable region (V1, V2, and V4 loop) of IDU.CON showed length variation compared with the heterosexual T/F virus consensus sequence (HSX.CON) and homosexual T/F virus consensus sequence (MSM.CON). 28073289 2 63 theme gp160 361:365 arg1 gene 367:370 full-length gp160 gene 349:370 full-length gp160 gene 349:370 We investigated a total of 749 sequences of full-length gp160 gene obtained by single genome sequencing (SGS) from 22 HIV-1 early infected IDUs in Xinjiang province, northwest China, and generated a transmitted and founder virus (T/F virus) consensus sequence (IDU.CON). 28073289 1 64 theme genetic 221:227 arg1 multiplicity 229:240 high genetic multiplicity 216:240 high genetic multiplicity 216:240 HIV-1 transmission in intravenous drug users (IDUs) has been characterized by high genetic multiplicity and suggests a greater challenge for HIV-1 infection blocking. 28073289 0 65 theme Virus 65:69 arg1 Sequence 81:88 and Founder Virus Consensus Sequence 53:88 Sequence 81:88 Generation and Characterization of HIV-1 Transmitted and Founder Virus Consensus Sequence from Intravenous Drug Users in Xinjiang, China. 28073289 6 66 theme virus 1087:1091 arg1 complexity 1073:1082 complexity 1073:1082 complexity 1073:1082 Characterization of T/F virus from IDUs highlights the genetic make-up and complexity of virus near the moment of transmission or in early infection preceding systemic dissemination and is important toward the development of an effective HIV-1 preventive methods, including vaccines. 28073289 6 66 theme virus 1087:1091 arg1 make-up 1061:1067 genetic make-up 1053:1067 genetic make-up 1053:1067 Characterization of T/F virus from IDUs highlights the genetic make-up and complexity of virus near the moment of transmission or in early infection preceding systemic dissemination and is important toward the development of an effective HIV-1 preventive methods, including vaccines. 28073289 6 67 from Characterization 998:1013 arg1 IDUs 1033:1036 IDUs 1033:1036 IDUs 1033:1036 Characterization of T/F virus from IDUs highlights the genetic make-up and complexity of virus near the moment of transmission or in early infection preceding systemic dissemination and is important toward the development of an effective HIV-1 preventive methods, including vaccines. 28073289 2 68 theme full-length 349:359 arg1 gene 367:370 full-length gp160 gene 349:370 full-length gp160 gene 349:370 We investigated a total of 749 sequences of full-length gp160 gene obtained by single genome sequencing (SGS) from 22 HIV-1 early infected IDUs in Xinjiang province, northwest China, and generated a transmitted and founder virus (T/F virus) consensus sequence (IDU.CON). 28073289 5 69 link 26 N-linked 877:887 arg1 sites 903:907 26 N-linked glycosylation sites 877:907 26 N-linked glycosylation sites 877:907 A total of 26 N-linked glycosylation sites were discovered in the IDU.CON sequence, which is less than that of MSM.CON and HSX.CON. 27175940 2 0 theme glycosylation 451:463 arg1 Ser110 417:422 Ser110 417:422 Ser110 417:422 The post-translational addition of O-GlcNAc to p27 occurs in HEK293T and HCC (hepatocellular carcinoma) cell lines, and we identified Ser2, Ser106, Ser110, Thr157, and Thr198 as the glycosylation sites of p27 based on the Q-TOF spectrum. 27175940 2 0 theme glycosylation 451:463 arg1 Thr157 425:430 Thr157 425:430 Thr157 425:430 The post-translational addition of O-GlcNAc to p27 occurs in HEK293T and HCC (hepatocellular carcinoma) cell lines, and we identified Ser2, Ser106, Ser110, Thr157, and Thr198 as the glycosylation sites of p27 based on the Q-TOF spectrum. 27175940 2 0 theme glycosylation 451:463 arg1 sites 465:469 the glycosylation sites 447:469 the glycosylation sites of p27 based on the Q-TOF spectrum 447:504 The post-translational addition of O-GlcNAc to p27 occurs in HEK293T and HCC (hepatocellular carcinoma) cell lines, and we identified Ser2, Ser106, Ser110, Thr157, and Thr198 as the glycosylation sites of p27 based on the Q-TOF spectrum. 27175940 2 0 theme glycosylation 451:463 arg1 Ser2 403:406 Ser2 403:406 Ser2 403:406 The post-translational addition of O-GlcNAc to p27 occurs in HEK293T and HCC (hepatocellular carcinoma) cell lines, and we identified Ser2, Ser106, Ser110, Thr157, and Thr198 as the glycosylation sites of p27 based on the Q-TOF spectrum. 27175940 2 0 theme glycosylation 451:463 arg1 Ser106 409:414 Ser106 409:414 Ser106 409:414 The post-translational addition of O-GlcNAc to p27 occurs in HEK293T and HCC (hepatocellular carcinoma) cell lines, and we identified Ser2, Ser106, Ser110, Thr157, and Thr198 as the glycosylation sites of p27 based on the Q-TOF spectrum. 27175940 2 0 theme glycosylation 451:463 arg1 Thr198 437:442 Thr198 437:442 Thr198 437:442 The post-translational addition of O-GlcNAc to p27 occurs in HEK293T and HCC (hepatocellular carcinoma) cell lines, and we identified Ser2, Ser106, Ser110, Thr157, and Thr198 as the glycosylation sites of p27 based on the Q-TOF spectrum. 27175940 2 0 theme glycosylation 451:463 arg1 p27 474:476 p27 474:476 p27 based on the Q-TOF spectrum 474:504 The post-translational addition of O-GlcNAc to p27 occurs in HEK293T and HCC (hepatocellular carcinoma) cell lines, and we identified Ser2, Ser106, Ser110, Thr157, and Thr198 as the glycosylation sites of p27 based on the Q-TOF spectrum. 27175940 4 1 theme nuclear 865:871 arg1 export 873:878 the nuclear export 861:878 the nuclear export of p27 861:885 In addition, O-GlcNAcylation at Ser2 suppressed Cyclin/CDK complex-p27 interactions by promoting the nuclear export of p27, thus facilitating cell cycle progression. 27175940 6 2 theme corresponding 1098:1110 arg1 tissues 1124:1130 their corresponding nontumorous tissues 1092:1130 their corresponding nontumorous tissues 1092:1130 Furthermore, western blot and immunohistochemical analyses of HCC tissues and their corresponding nontumorous tissues were performed, and we found that O-GlcNAcylated p27 correlated with cell proliferation in HCC. 27175940 6 3 from proliferation 1206:1218 arg1 HCC 1223:1225 HCC 1223:1225 HCC 1223:1225 Furthermore, western blot and immunohistochemical analyses of HCC tissues and their corresponding nontumorous tissues were performed, and we found that O-GlcNAcylated p27 correlated with cell proliferation in HCC. 27175940 1 4 theme anti-proliferative 242:259 arg1 events 261:266 anti-proliferative events 242:266 anti-proliferative events 242:266 The tumor suppressor p27, which is a member of the Cip/Kip family of Cyclin-dependent kinase inhibitory proteins (CKIs), controls anti-proliferative events. 27175940 0 5 theme hepatocellular 86:99 arg1 carcinoma 101:109 hepatocellular carcinoma 86:109 hepatocellular carcinoma 86:109 Modification of p27 with O-linked N-acetylglucosamine regulates cell proliferation in hepatocellular carcinoma. 27175940 2 6 theme hepatocellular 347:360 arg1 carcinoma 362:370 hepatocellular carcinoma 347:370 hepatocellular carcinoma 347:370 The post-translational addition of O-GlcNAc to p27 occurs in HEK293T and HCC (hepatocellular carcinoma) cell lines, and we identified Ser2, Ser106, Ser110, Thr157, and Thr198 as the glycosylation sites of p27 based on the Q-TOF spectrum. 27175940 2 6 theme hepatocellular 347:360 arg1 HEK293T 330:336 HEK293T 330:336 HEK293T 330:336 The post-translational addition of O-GlcNAc to p27 occurs in HEK293T and HCC (hepatocellular carcinoma) cell lines, and we identified Ser2, Ser106, Ser110, Thr157, and Thr198 as the glycosylation sites of p27 based on the Q-TOF spectrum. 27175940 2 7 theme O-GlcNAc 304:311 arg1 addition 292:299 The post-translational addition 269:299 The post-translational addition of O-GlcNAc to p27 269:318 The post-translational addition of O-GlcNAc to p27 occurs in HEK293T and HCC (hepatocellular carcinoma) cell lines, and we identified Ser2, Ser106, Ser110, Thr157, and Thr198 as the glycosylation sites of p27 based on the Q-TOF spectrum. 27175940 2 8 gly glycosylation 451:463 arg2 Ser106 409:414 Ser106 409:414 Ser106 409:414 The post-translational addition of O-GlcNAc to p27 occurs in HEK293T and HCC (hepatocellular carcinoma) cell lines, and we identified Ser2, Ser106, Ser110, Thr157, and Thr198 as the glycosylation sites of p27 based on the Q-TOF spectrum. 27175940 2 8 gly glycosylation 451:463 arg2 sites 465:469 the glycosylation sites 447:469 the glycosylation sites of p27 based on the Q-TOF spectrum 447:504 The post-translational addition of O-GlcNAc to p27 occurs in HEK293T and HCC (hepatocellular carcinoma) cell lines, and we identified Ser2, Ser106, Ser110, Thr157, and Thr198 as the glycosylation sites of p27 based on the Q-TOF spectrum. 27175940 2 8 gly glycosylation 451:463 arg2 Thr198 437:442 Thr198 437:442 Thr198 437:442 The post-translational addition of O-GlcNAc to p27 occurs in HEK293T and HCC (hepatocellular carcinoma) cell lines, and we identified Ser2, Ser106, Ser110, Thr157, and Thr198 as the glycosylation sites of p27 based on the Q-TOF spectrum. 27175940 2 8 gly glycosylation 451:463 arg2 p27 474:476 p27 474:476 p27 based on the Q-TOF spectrum 474:504 The post-translational addition of O-GlcNAc to p27 occurs in HEK293T and HCC (hepatocellular carcinoma) cell lines, and we identified Ser2, Ser106, Ser110, Thr157, and Thr198 as the glycosylation sites of p27 based on the Q-TOF spectrum. 27175940 2 8 gly glycosylation 451:463 arg2 Ser110 417:422 Ser110 417:422 Ser110 417:422 The post-translational addition of O-GlcNAc to p27 occurs in HEK293T and HCC (hepatocellular carcinoma) cell lines, and we identified Ser2, Ser106, Ser110, Thr157, and Thr198 as the glycosylation sites of p27 based on the Q-TOF spectrum. 27175940 2 8 gly glycosylation 451:463 arg2 Ser2 403:406 Ser2 403:406 Ser2 403:406 The post-translational addition of O-GlcNAc to p27 occurs in HEK293T and HCC (hepatocellular carcinoma) cell lines, and we identified Ser2, Ser106, Ser110, Thr157, and Thr198 as the glycosylation sites of p27 based on the Q-TOF spectrum. 27175940 2 8 gly glycosylation 451:463 arg2 Thr157 425:430 Thr157 425:430 Thr157 425:430 The post-translational addition of O-GlcNAc to p27 occurs in HEK293T and HCC (hepatocellular carcinoma) cell lines, and we identified Ser2, Ser106, Ser110, Thr157, and Thr198 as the glycosylation sites of p27 based on the Q-TOF spectrum. 27175940 2 8 gly glycosylation 451:463 arg1 p27 474:476 p27 474:476 p27 based on the Q-TOF spectrum 474:504 The post-translational addition of O-GlcNAc to p27 occurs in HEK293T and HCC (hepatocellular carcinoma) cell lines, and we identified Ser2, Ser106, Ser110, Thr157, and Thr198 as the glycosylation sites of p27 based on the Q-TOF spectrum. 27175940 6 9 theme O-GlcNAcylated 1166:1179 arg1 p27 1181:1183 O-GlcNAcylated p27 1166:1183 O-GlcNAcylated p27 1166:1183 Furthermore, western blot and immunohistochemical analyses of HCC tissues and their corresponding nontumorous tissues were performed, and we found that O-GlcNAcylated p27 correlated with cell proliferation in HCC. 27175940 3 10 theme p27 696:698 arg1 accumulation 700:711 p27 accumulation 696:711 p27 accumulation 696:711 Here, immunoprecipitation analysis showed that Ser2 was O-GlcNAcylated and that this modification was associated with the increased phosphorylation of p27 at Ser10, ultimately resulting in p27 accumulation in the cytoplasm and increased p27 ubiquitination. 27175940 6 11 theme immunohistochemical 1044:1062 arg1 analyses 1064:1071 immunohistochemical analyses 1044:1071 immunohistochemical analyses of HCC tissues and their corresponding nontumorous tissues 1044:1130 Furthermore, western blot and immunohistochemical analyses of HCC tissues and their corresponding nontumorous tissues were performed, and we found that O-GlcNAcylated p27 correlated with cell proliferation in HCC. 27175940 7 12 dep O-GlcNAcylation 1294:1308 arg1 phosphorylation 1318:1332 phosphorylation 1318:1332 phosphorylation 1318:1332 Together, our results indicate that the dynamic interplay between O-GlcNAcylation and p27 phosphorylation coordinates and regulates cell proliferation in hepatocellular carcinoma. 27175940 1 13 theme Cip/Kip 163:169 arg1 family 171:176 the Cip/Kip family 159:176 the Cip/Kip family of Cyclin-dependent kinase inhibitory proteins (CKIs) 159:230 The tumor suppressor p27, which is a member of the Cip/Kip family of Cyclin-dependent kinase inhibitory proteins (CKIs), controls anti-proliferative events. 27175940 2 14 theme p27 474:476 arg1 Ser110 417:422 Ser110 417:422 Ser110 417:422 The post-translational addition of O-GlcNAc to p27 occurs in HEK293T and HCC (hepatocellular carcinoma) cell lines, and we identified Ser2, Ser106, Ser110, Thr157, and Thr198 as the glycosylation sites of p27 based on the Q-TOF spectrum. 27175940 2 14 theme p27 474:476 arg1 Thr157 425:430 Thr157 425:430 Thr157 425:430 The post-translational addition of O-GlcNAc to p27 occurs in HEK293T and HCC (hepatocellular carcinoma) cell lines, and we identified Ser2, Ser106, Ser110, Thr157, and Thr198 as the glycosylation sites of p27 based on the Q-TOF spectrum. 27175940 2 14 theme p27 474:476 arg1 sites 465:469 the glycosylation sites 447:469 the glycosylation sites of p27 based on the Q-TOF spectrum 447:504 The post-translational addition of O-GlcNAc to p27 occurs in HEK293T and HCC (hepatocellular carcinoma) cell lines, and we identified Ser2, Ser106, Ser110, Thr157, and Thr198 as the glycosylation sites of p27 based on the Q-TOF spectrum. 27175940 2 14 theme p27 474:476 arg1 Ser2 403:406 Ser2 403:406 Ser2 403:406 The post-translational addition of O-GlcNAc to p27 occurs in HEK293T and HCC (hepatocellular carcinoma) cell lines, and we identified Ser2, Ser106, Ser110, Thr157, and Thr198 as the glycosylation sites of p27 based on the Q-TOF spectrum. 27175940 2 14 theme p27 474:476 arg1 Ser106 409:414 Ser106 409:414 Ser106 409:414 The post-translational addition of O-GlcNAc to p27 occurs in HEK293T and HCC (hepatocellular carcinoma) cell lines, and we identified Ser2, Ser106, Ser110, Thr157, and Thr198 as the glycosylation sites of p27 based on the Q-TOF spectrum. 27175940 2 14 theme p27 474:476 arg1 Thr198 437:442 Thr198 437:442 Thr198 437:442 The post-translational addition of O-GlcNAc to p27 occurs in HEK293T and HCC (hepatocellular carcinoma) cell lines, and we identified Ser2, Ser106, Ser110, Thr157, and Thr198 as the glycosylation sites of p27 based on the Q-TOF spectrum. 27175940 2 14 theme p27 474:476 arg1 p27 474:476 p27 474:476 p27 based on the Q-TOF spectrum 474:504 The post-translational addition of O-GlcNAc to p27 occurs in HEK293T and HCC (hepatocellular carcinoma) cell lines, and we identified Ser2, Ser106, Ser110, Thr157, and Thr198 as the glycosylation sites of p27 based on the Q-TOF spectrum. 27175940 4 15 theme complex-p27 823:833 arg1 interactions 835:846 Cyclin/CDK complex-p27 interactions 812:846 Cyclin/CDK complex-p27 interactions 812:846 In addition, O-GlcNAcylation at Ser2 suppressed Cyclin/CDK complex-p27 interactions by promoting the nuclear export of p27, thus facilitating cell cycle progression. 27175940 2 16 theme post-translational 273:290 arg1 addition 292:299 The post-translational addition 269:299 The post-translational addition of O-GlcNAc to p27 269:318 The post-translational addition of O-GlcNAc to p27 occurs in HEK293T and HCC (hepatocellular carcinoma) cell lines, and we identified Ser2, Ser106, Ser110, Thr157, and Thr198 as the glycosylation sites of p27 based on the Q-TOF spectrum. 27175940 1 17 theme family 171:176 arg1 member 149:154 a member 147:154 a member of the Cip/Kip family of Cyclin-dependent kinase inhibitory proteins (CKIs) 147:230 The tumor suppressor p27, which is a member of the Cip/Kip family of Cyclin-dependent kinase inhibitory proteins (CKIs), controls anti-proliferative events. 27175940 1 17 theme family 171:176 arg1 p27 133:135 The tumor suppressor p27 112:135 The tumor suppressor p27 112:135 The tumor suppressor p27, which is a member of the Cip/Kip family of Cyclin-dependent kinase inhibitory proteins (CKIs), controls anti-proliferative events. 27175940 7 18 theme dynamic 1268:1274 arg1 interplay 1276:1284 the dynamic interplay 1264:1284 the dynamic interplay between O-GlcNAcylation and p27 phosphorylation 1264:1332 Together, our results indicate that the dynamic interplay between O-GlcNAcylation and p27 phosphorylation coordinates and regulates cell proliferation in hepatocellular carcinoma. 27175940 5 19 theme Cell 930:933 arg1 proliferation 935:947 Cell proliferation 930:947 Cell proliferation 930:947 Cell proliferation was negatively regulated when Ser2 of p27 was replaced with Ala. 27175940 6 20 theme HCC 1076:1078 arg1 tissues 1080:1086 HCC tissues 1076:1086 HCC tissues 1076:1086 Furthermore, western blot and immunohistochemical analyses of HCC tissues and their corresponding nontumorous tissues were performed, and we found that O-GlcNAcylated p27 correlated with cell proliferation in HCC. 27175940 3 21 theme immunoprecipitation 513:531 arg1 analysis 533:540 immunoprecipitation analysis 513:540 immunoprecipitation analysis 513:540 Here, immunoprecipitation analysis showed that Ser2 was O-GlcNAcylated and that this modification was associated with the increased phosphorylation of p27 at Ser10, ultimately resulting in p27 accumulation in the cytoplasm and increased p27 ubiquitination. 27175940 1 22 theme Cyclin-dependent 181:196 arg1 CKIs 226:229 CKIs 226:229 CKIs 226:229 The tumor suppressor p27, which is a member of the Cip/Kip family of Cyclin-dependent kinase inhibitory proteins (CKIs), controls anti-proliferative events. 27175940 1 22 theme Cyclin-dependent 181:196 arg1 proteins 216:223 Cyclin-dependent kinase inhibitory proteins 181:223 Cyclin-dependent kinase inhibitory proteins (CKIs) 181:230 The tumor suppressor p27, which is a member of the Cip/Kip family of Cyclin-dependent kinase inhibitory proteins (CKIs), controls anti-proliferative events. 27175940 4 23 theme cycle 911:915 arg1 progression 917:927 cell cycle progression 906:927 cell cycle progression 906:927 In addition, O-GlcNAcylation at Ser2 suppressed Cyclin/CDK complex-p27 interactions by promoting the nuclear export of p27, thus facilitating cell cycle progression. 27175940 0 24 link O-linked 25:32 arg1 N-acetylglucosamine 34:52 O-linked N-acetylglucosamine 25:52 O-linked N-acetylglucosamine 25:52 Modification of p27 with O-linked N-acetylglucosamine regulates cell proliferation in hepatocellular carcinoma. 27175940 1 25 theme tumor 116:120 arg1 member 149:154 a member 147:154 a member of the Cip/Kip family of Cyclin-dependent kinase inhibitory proteins (CKIs) 147:230 The tumor suppressor p27, which is a member of the Cip/Kip family of Cyclin-dependent kinase inhibitory proteins (CKIs), controls anti-proliferative events. 27175940 1 25 theme tumor 116:120 arg1 p27 133:135 The tumor suppressor p27 112:135 The tumor suppressor p27 112:135 The tumor suppressor p27, which is a member of the Cip/Kip family of Cyclin-dependent kinase inhibitory proteins (CKIs), controls anti-proliferative events. 27175940 1 26 theme kinase 198:203 arg1 CKIs 226:229 CKIs 226:229 CKIs 226:229 The tumor suppressor p27, which is a member of the Cip/Kip family of Cyclin-dependent kinase inhibitory proteins (CKIs), controls anti-proliferative events. 27175940 1 26 theme kinase 198:203 arg1 proteins 216:223 Cyclin-dependent kinase inhibitory proteins 181:223 Cyclin-dependent kinase inhibitory proteins (CKIs) 181:230 The tumor suppressor p27, which is a member of the Cip/Kip family of Cyclin-dependent kinase inhibitory proteins (CKIs), controls anti-proliferative events. 27175940 0 27 theme p27 16:18 arg1 Modification 0:11 Modification 0:11 Modification of p27 with O-linked N-acetylglucosamine 0:52 Modification of p27 with O-linked N-acetylglucosamine regulates cell proliferation in hepatocellular carcinoma. 27175940 4 28 theme cell 906:909 arg1 progression 917:927 cell cycle progression 906:927 cell cycle progression 906:927 In addition, O-GlcNAcylation at Ser2 suppressed Cyclin/CDK complex-p27 interactions by promoting the nuclear export of p27, thus facilitating cell cycle progression. 27175940 1 29 theme suppressor 122:131 arg1 member 149:154 a member 147:154 a member of the Cip/Kip family of Cyclin-dependent kinase inhibitory proteins (CKIs) 147:230 The tumor suppressor p27, which is a member of the Cip/Kip family of Cyclin-dependent kinase inhibitory proteins (CKIs), controls anti-proliferative events. 27175940 1 29 theme suppressor 122:131 arg1 p27 133:135 The tumor suppressor p27 112:135 The tumor suppressor p27 112:135 The tumor suppressor p27, which is a member of the Cip/Kip family of Cyclin-dependent kinase inhibitory proteins (CKIs), controls anti-proliferative events. 27175940 1 30 theme inhibitory 205:214 arg1 CKIs 226:229 CKIs 226:229 CKIs 226:229 The tumor suppressor p27, which is a member of the Cip/Kip family of Cyclin-dependent kinase inhibitory proteins (CKIs), controls anti-proliferative events. 27175940 1 30 theme inhibitory 205:214 arg1 proteins 216:223 Cyclin-dependent kinase inhibitory proteins 181:223 Cyclin-dependent kinase inhibitory proteins (CKIs) 181:230 The tumor suppressor p27, which is a member of the Cip/Kip family of Cyclin-dependent kinase inhibitory proteins (CKIs), controls anti-proliferative events. 27175940 7 31 theme cell 1360:1363 arg1 proliferation 1365:1377 cell proliferation 1360:1377 cell proliferation 1360:1377 Together, our results indicate that the dynamic interplay between O-GlcNAcylation and p27 phosphorylation coordinates and regulates cell proliferation in hepatocellular carcinoma. 27175940 1 32 theme proteins 216:223 arg1 family 171:176 the Cip/Kip family 159:176 the Cip/Kip family of Cyclin-dependent kinase inhibitory proteins (CKIs) 159:230 The tumor suppressor p27, which is a member of the Cip/Kip family of Cyclin-dependent kinase inhibitory proteins (CKIs), controls anti-proliferative events. 27175940 0 33 theme O-linked 25:32 arg1 N-acetylglucosamine 34:52 O-linked N-acetylglucosamine 25:52 O-linked N-acetylglucosamine 25:52 Modification of p27 with O-linked N-acetylglucosamine regulates cell proliferation in hepatocellular carcinoma. 27175940 3 34 from Ser10 665:669 arg1 phosphorylation 639:653 the increased phosphorylation 625:653 the increased phosphorylation of p27 at Ser10 625:669 Here, immunoprecipitation analysis showed that Ser2 was O-GlcNAcylated and that this modification was associated with the increased phosphorylation of p27 at Ser10, ultimately resulting in p27 accumulation in the cytoplasm and increased p27 ubiquitination. 27175940 2 35 theme Q-TOF 491:495 arg1 spectrum 497:504 the Q-TOF spectrum 487:504 the Q-TOF spectrum 487:504 The post-translational addition of O-GlcNAc to p27 occurs in HEK293T and HCC (hepatocellular carcinoma) cell lines, and we identified Ser2, Ser106, Ser110, Thr157, and Thr198 as the glycosylation sites of p27 based on the Q-TOF spectrum. 27175940 0 36 theme cell 64:67 arg1 proliferation 69:81 cell proliferation 64:81 cell proliferation 64:81 Modification of p27 with O-linked N-acetylglucosamine regulates cell proliferation in hepatocellular carcinoma. 27175940 6 37 theme tissues 1124:1130 arg1 blot 1035:1038 western blot 1027:1038 western blot 1027:1038 Furthermore, western blot and immunohistochemical analyses of HCC tissues and their corresponding nontumorous tissues were performed, and we found that O-GlcNAcylated p27 correlated with cell proliferation in HCC. 27175940 6 37 theme tissues 1124:1130 arg1 analyses 1064:1071 immunohistochemical analyses 1044:1071 immunohistochemical analyses of HCC tissues and their corresponding nontumorous tissues 1044:1130 Furthermore, western blot and immunohistochemical analyses of HCC tissues and their corresponding nontumorous tissues were performed, and we found that O-GlcNAcylated p27 correlated with cell proliferation in HCC. 27175940 4 38 theme p27 883:885 arg1 export 873:878 the nuclear export 861:878 the nuclear export of p27 861:885 In addition, O-GlcNAcylation at Ser2 suppressed Cyclin/CDK complex-p27 interactions by promoting the nuclear export of p27, thus facilitating cell cycle progression. 27175940 4 39 from Ser2 796:799 arg1 O-GlcNAcylation 777:791 O-GlcNAcylation 777:791 O-GlcNAcylation at Ser2 777:799 In addition, O-GlcNAcylation at Ser2 suppressed Cyclin/CDK complex-p27 interactions by promoting the nuclear export of p27, thus facilitating cell cycle progression. 27175940 2 40 theme HCC 342:344 arg1 lines 378:382 HEK293T and HCC (hepatocellular carcinoma) cell lines 330:382 HEK293T and HCC (hepatocellular carcinoma) cell lines 330:382 The post-translational addition of O-GlcNAc to p27 occurs in HEK293T and HCC (hepatocellular carcinoma) cell lines, and we identified Ser2, Ser106, Ser110, Thr157, and Thr198 as the glycosylation sites of p27 based on the Q-TOF spectrum. 27175940 3 41 theme p27 744:746 arg1 ubiquitination 748:761 p27 ubiquitination 744:761 p27 ubiquitination 744:761 Here, immunoprecipitation analysis showed that Ser2 was O-GlcNAcylated and that this modification was associated with the increased phosphorylation of p27 at Ser10, ultimately resulting in p27 accumulation in the cytoplasm and increased p27 ubiquitination. 27175940 3 42 theme p27 658:660 arg1 phosphorylation 639:653 the increased phosphorylation 625:653 the increased phosphorylation of p27 at Ser10 625:669 Here, immunoprecipitation analysis showed that Ser2 was O-GlcNAcylated and that this modification was associated with the increased phosphorylation of p27 at Ser10, ultimately resulting in p27 accumulation in the cytoplasm and increased p27 ubiquitination. 27175940 5 43 theme p27 987:989 arg1 Ser2 979:982 Ser2 979:982 Ser2 of p27 979:989 Cell proliferation was negatively regulated when Ser2 of p27 was replaced with Ala. 27175940 0 44 with Modification 0:11 arg1 N-acetylglucosamine 34:52 O-linked N-acetylglucosamine 25:52 O-linked N-acetylglucosamine 25:52 Modification of p27 with O-linked N-acetylglucosamine regulates cell proliferation in hepatocellular carcinoma. 27175940 6 45 theme western 1027:1033 arg1 blot 1035:1038 western blot 1027:1038 western blot 1027:1038 Furthermore, western blot and immunohistochemical analyses of HCC tissues and their corresponding nontumorous tissues were performed, and we found that O-GlcNAcylated p27 correlated with cell proliferation in HCC. 27175940 3 46 theme increased 629:637 arg1 phosphorylation 639:653 the increased phosphorylation 625:653 the increased phosphorylation of p27 at Ser10 625:669 Here, immunoprecipitation analysis showed that Ser2 was O-GlcNAcylated and that this modification was associated with the increased phosphorylation of p27 at Ser10, ultimately resulting in p27 accumulation in the cytoplasm and increased p27 ubiquitination. 27175940 6 47 theme cell 1201:1204 arg1 proliferation 1206:1218 cell proliferation 1201:1218 cell proliferation in HCC 1201:1225 Furthermore, western blot and immunohistochemical analyses of HCC tissues and their corresponding nontumorous tissues were performed, and we found that O-GlcNAcylated p27 correlated with cell proliferation in HCC. 27175940 2 48 theme HEK293T 330:336 arg1 lines 378:382 HEK293T and HCC (hepatocellular carcinoma) cell lines 330:382 HEK293T and HCC (hepatocellular carcinoma) cell lines 330:382 The post-translational addition of O-GlcNAc to p27 occurs in HEK293T and HCC (hepatocellular carcinoma) cell lines, and we identified Ser2, Ser106, Ser110, Thr157, and Thr198 as the glycosylation sites of p27 based on the Q-TOF spectrum. 27175940 7 49 theme hepatocellular 1382:1395 arg1 carcinoma 1397:1405 hepatocellular carcinoma 1382:1405 hepatocellular carcinoma 1382:1405 Together, our results indicate that the dynamic interplay between O-GlcNAcylation and p27 phosphorylation coordinates and regulates cell proliferation in hepatocellular carcinoma. 27175940 8 50 dep © 1408:1408 arg1 Inc. 1434:1437 Inc. 1434:1437 Inc. 1434:1437 © 2016 Wiley Periodicals, Inc. 27175940 2 51 theme cell 373:376 arg1 lines 378:382 HEK293T and HCC (hepatocellular carcinoma) cell lines 330:382 HEK293T and HCC (hepatocellular carcinoma) cell lines 330:382 The post-translational addition of O-GlcNAc to p27 occurs in HEK293T and HCC (hepatocellular carcinoma) cell lines, and we identified Ser2, Ser106, Ser110, Thr157, and Thr198 as the glycosylation sites of p27 based on the Q-TOF spectrum. 27175940 6 52 theme tissues 1080:1086 arg1 blot 1035:1038 western blot 1027:1038 western blot 1027:1038 Furthermore, western blot and immunohistochemical analyses of HCC tissues and their corresponding nontumorous tissues were performed, and we found that O-GlcNAcylated p27 correlated with cell proliferation in HCC. 27175940 6 52 theme tissues 1080:1086 arg1 analyses 1064:1071 immunohistochemical analyses 1044:1071 immunohistochemical analyses of HCC tissues and their corresponding nontumorous tissues 1044:1130 Furthermore, western blot and immunohistochemical analyses of HCC tissues and their corresponding nontumorous tissues were performed, and we found that O-GlcNAcylated p27 correlated with cell proliferation in HCC. 27175940 6 53 theme nontumorous 1112:1122 arg1 tissues 1124:1130 their corresponding nontumorous tissues 1092:1130 their corresponding nontumorous tissues 1092:1130 Furthermore, western blot and immunohistochemical analyses of HCC tissues and their corresponding nontumorous tissues were performed, and we found that O-GlcNAcylated p27 correlated with cell proliferation in HCC. 27342663 5 0 theme glycosylation 1222:1234 arg1 chain 1254:1258 the heavy chain 1244:1258 the heavy chain 1244:1258 The large majority of the glycoforms present on the single, conserved N-linked glycosylation site of the heavy chain is elucidated, although some of the very low abundance glycoforms are not determined by this protocol. 27342663 5 0 theme glycosylation 1222:1234 arg1 site 1236:1239 the single, conserved N-linked glycosylation site 1191:1239 the single, conserved N-linked glycosylation site of the heavy chain 1191:1258 The large majority of the glycoforms present on the single, conserved N-linked glycosylation site of the heavy chain is elucidated, although some of the very low abundance glycoforms are not determined by this protocol. 27342663 5 1 attach present 1180:1186 arg1 chain 1254:1258 the heavy chain 1244:1258 the heavy chain 1244:1258 The large majority of the glycoforms present on the single, conserved N-linked glycosylation site of the heavy chain is elucidated, although some of the very low abundance glycoforms are not determined by this protocol. 27342663 5 1 attach present 1180:1186 arg2 glycoforms 1169:1178 the glycoforms 1165:1178 the glycoforms present on the single, conserved N-linked glycosylation site of the heavy chain 1165:1258 The large majority of the glycoforms present on the single, conserved N-linked glycosylation site of the heavy chain is elucidated, although some of the very low abundance glycoforms are not determined by this protocol. 27342663 5 1 attach present 1180:1186 arg1 site 1236:1239 the single, conserved N-linked glycosylation site 1191:1239 the single, conserved N-linked glycosylation site of the heavy chain 1191:1258 The large majority of the glycoforms present on the single, conserved N-linked glycosylation site of the heavy chain is elucidated, although some of the very low abundance glycoforms are not determined by this protocol. 27342663 0 2 theme spectral 85:92 arg1 analysis 94:101 single sample mass spectral analysis 66:101 single sample mass spectral analysis after IdeS proteolysis 66:124 Structural characterization of expressed monoclonal antibodies by single sample mass spectral analysis after IdeS proteolysis. 27342663 4 3 theme simple 957:962 arg1 introduction 964:975 simple introduction 957:975 simple introduction of a single, unseparated mixture of alkylated fragments into a mass spectrometer 957:1056 In this study, we coupled IdeS fragmentation and simultaneous reduction and alkylation of the resultant fragments using tributylphosphine and iodoacetamide to prepare samples in about 2 h. Following simple introduction of a single, unseparated mixture of alkylated fragments into a mass spectrometer, detailed structural information is obtained, covering the entire antibody molecule. 27342663 5 4 gly glycoforms 1315:1324 arg1 abundance 1305:1313 the very low abundance glycoforms 1292:1324 the very low abundance glycoforms 1292:1324 The large majority of the glycoforms present on the single, conserved N-linked glycosylation site of the heavy chain is elucidated, although some of the very low abundance glycoforms are not determined by this protocol. 27342663 1 5 theme monoclonal 168:177 arg1 antibody 179:186 monoclonal antibody 168:186 monoclonal antibody structure 168:196 Simple and rapid methods for analysis of monoclonal antibody structure and post-translational modifications are increasingly needed due to the explosion of therapeutic monoclonal antibodies and monoclonal antibody applications. 27342663 1 6 theme therapeutic 283:293 arg1 antibodies 306:315 therapeutic monoclonal antibodies 283:315 therapeutic monoclonal antibodies 283:315 Simple and rapid methods for analysis of monoclonal antibody structure and post-translational modifications are increasingly needed due to the explosion of therapeutic monoclonal antibodies and monoclonal antibody applications. 27342663 0 7 theme IdeS 109:112 arg1 proteolysis 114:124 IdeS proteolysis 109:124 IdeS proteolysis 109:124 Structural characterization of expressed monoclonal antibodies by single sample mass spectral analysis after IdeS proteolysis. 27342663 4 8 theme fragments 862:870 arg1 reduction 820:828 simultaneous reduction 807:828 simultaneous reduction 807:828 In this study, we coupled IdeS fragmentation and simultaneous reduction and alkylation of the resultant fragments using tributylphosphine and iodoacetamide to prepare samples in about 2 h. Following simple introduction of a single, unseparated mixture of alkylated fragments into a mass spectrometer, detailed structural information is obtained, covering the entire antibody molecule. 27342663 4 8 theme fragments 862:870 arg1 alkylation 834:843 alkylation 834:843 alkylation 834:843 In this study, we coupled IdeS fragmentation and simultaneous reduction and alkylation of the resultant fragments using tributylphosphine and iodoacetamide to prepare samples in about 2 h. Following simple introduction of a single, unseparated mixture of alkylated fragments into a mass spectrometer, detailed structural information is obtained, covering the entire antibody molecule. 27342663 4 8 theme fragments 862:870 arg1 fragmentation 789:801 IdeS fragmentation 784:801 IdeS fragmentation 784:801 In this study, we coupled IdeS fragmentation and simultaneous reduction and alkylation of the resultant fragments using tributylphosphine and iodoacetamide to prepare samples in about 2 h. Following simple introduction of a single, unseparated mixture of alkylated fragments into a mass spectrometer, detailed structural information is obtained, covering the entire antibody molecule. 27342663 6 9 theme stages 1470:1475 arg1 analysis 1440:1447 analysis 1440:1447 analysis of the developmental stages and production batches of therapeutic monoclonal antibodies 1440:1535 The ease, simplicity, speed, and power of this method make it attractive for analysis of the developmental stages and production batches of therapeutic monoclonal antibodies. 27342663 6 10 theme antibodies 1526:1535 arg1 stages 1470:1475 developmental stages 1456:1475 developmental stages 1456:1475 The ease, simplicity, speed, and power of this method make it attractive for analysis of the developmental stages and production batches of therapeutic monoclonal antibodies. 27342663 6 10 theme antibodies 1526:1535 arg1 batches 1492:1498 production batches 1481:1498 production batches 1481:1498 The ease, simplicity, speed, and power of this method make it attractive for analysis of the developmental stages and production batches of therapeutic monoclonal antibodies. 27342663 1 11 theme monoclonal 295:304 arg1 antibodies 306:315 therapeutic monoclonal antibodies 283:315 therapeutic monoclonal antibodies 283:315 Simple and rapid methods for analysis of monoclonal antibody structure and post-translational modifications are increasingly needed due to the explosion of therapeutic monoclonal antibodies and monoclonal antibody applications. 27342663 4 12 theme entire 1117:1122 arg1 molecule 1133:1140 the entire antibody molecule 1113:1140 the entire antibody molecule 1113:1140 In this study, we coupled IdeS fragmentation and simultaneous reduction and alkylation of the resultant fragments using tributylphosphine and iodoacetamide to prepare samples in about 2 h. Following simple introduction of a single, unseparated mixture of alkylated fragments into a mass spectrometer, detailed structural information is obtained, covering the entire antibody molecule. 27342663 3 13 theme suitable 631:638 arg1 size 640:643 suitable size 631:643 suitable size 631:643 Recent discovery and commercialization of the Immunoglobulin G-degrading enzyme of Streptococcus pyogene (IdeS protease) has facilitated and improved the generation of antibody fragments of suitable size to allow characterization of the structure of the entire antibody molecule via analysis of just a few fragments. 27342663 5 14 gly glycosylation 1222:1234 arg1 chain 1254:1258 the heavy chain 1244:1258 the heavy chain 1244:1258 The large majority of the glycoforms present on the single, conserved N-linked glycosylation site of the heavy chain is elucidated, although some of the very low abundance glycoforms are not determined by this protocol. 27342663 5 14 gly glycosylation 1222:1234 arg2 site 1236:1239 the single, conserved N-linked glycosylation site 1191:1239 the single, conserved N-linked glycosylation site of the heavy chain 1191:1258 The large majority of the glycoforms present on the single, conserved N-linked glycosylation site of the heavy chain is elucidated, although some of the very low abundance glycoforms are not determined by this protocol. 27342663 5 14 gly glycosylation 1222:1234 arg2 chain 1254:1258 the heavy chain 1244:1258 the heavy chain 1244:1258 The large majority of the glycoforms present on the single, conserved N-linked glycosylation site of the heavy chain is elucidated, although some of the very low abundance glycoforms are not determined by this protocol. 27342663 1 15 theme antibodies 306:315 arg1 explosion 270:278 the explosion 266:278 the explosion of therapeutic monoclonal antibodies and monoclonal antibody applications 266:352 Simple and rapid methods for analysis of monoclonal antibody structure and post-translational modifications are increasingly needed due to the explosion of therapeutic monoclonal antibodies and monoclonal antibody applications. 27342663 5 16 theme single 1195:1200 arg1 chain 1254:1258 the heavy chain 1244:1258 the heavy chain 1244:1258 The large majority of the glycoforms present on the single, conserved N-linked glycosylation site of the heavy chain is elucidated, although some of the very low abundance glycoforms are not determined by this protocol. 27342663 5 16 theme single 1195:1200 arg1 site 1236:1239 the single, conserved N-linked glycosylation site 1191:1239 the single, conserved N-linked glycosylation site of the heavy chain 1191:1258 The large majority of the glycoforms present on the single, conserved N-linked glycosylation site of the heavy chain is elucidated, although some of the very low abundance glycoforms are not determined by this protocol. 27342663 3 17 theme antibody 609:616 arg1 fragments 618:626 antibody fragments 609:626 antibody fragments of suitable size 609:643 Recent discovery and commercialization of the Immunoglobulin G-degrading enzyme of Streptococcus pyogene (IdeS protease) has facilitated and improved the generation of antibody fragments of suitable size to allow characterization of the structure of the entire antibody molecule via analysis of just a few fragments. 27342663 1 18 theme antibody 179:186 arg1 structure 188:196 monoclonal antibody structure 168:196 monoclonal antibody structure 168:196 Simple and rapid methods for analysis of monoclonal antibody structure and post-translational modifications are increasingly needed due to the explosion of therapeutic monoclonal antibodies and monoclonal antibody applications. 27342663 5 19 theme low 1301:1303 arg1 glycoforms 1315:1324 the very low abundance glycoforms 1292:1324 the very low abundance glycoforms 1292:1324 The large majority of the glycoforms present on the single, conserved N-linked glycosylation site of the heavy chain is elucidated, although some of the very low abundance glycoforms are not determined by this protocol. 27342663 6 20 dep stages 1470:1475 arg1 the 1452:1454 the 1452:1454 the 1452:1454 The ease, simplicity, speed, and power of this method make it attractive for analysis of the developmental stages and production batches of therapeutic monoclonal antibodies. 27342663 6 21 theme production 1481:1490 arg1 batches 1492:1498 production batches 1481:1498 production batches 1481:1498 The ease, simplicity, speed, and power of this method make it attractive for analysis of the developmental stages and production batches of therapeutic monoclonal antibodies. 27342663 3 22 theme fragments 618:626 arg1 generation 595:604 the generation 591:604 the generation of antibody fragments of suitable size to allow characterization of the structure of the entire antibody molecule via analysis of just a few fragments 591:755 Recent discovery and commercialization of the Immunoglobulin G-degrading enzyme of Streptococcus pyogene (IdeS protease) has facilitated and improved the generation of antibody fragments of suitable size to allow characterization of the structure of the entire antibody molecule via analysis of just a few fragments. 27342663 1 23 theme structure 188:196 arg1 analysis 156:163 analysis 156:163 analysis of monoclonal antibody structure and post-translational modifications 156:233 Simple and rapid methods for analysis of monoclonal antibody structure and post-translational modifications are increasingly needed due to the explosion of therapeutic monoclonal antibodies and monoclonal antibody applications. 27342663 4 24 theme antibody 1124:1131 arg1 molecule 1133:1140 the entire antibody molecule 1113:1140 the entire antibody molecule 1113:1140 In this study, we coupled IdeS fragmentation and simultaneous reduction and alkylation of the resultant fragments using tributylphosphine and iodoacetamide to prepare samples in about 2 h. Following simple introduction of a single, unseparated mixture of alkylated fragments into a mass spectrometer, detailed structural information is obtained, covering the entire antibody molecule. 27342663 4 25 dep single 982:987 arg1 unseparated 990:1000 unseparated 990:1000 unseparated 990:1000 In this study, we coupled IdeS fragmentation and simultaneous reduction and alkylation of the resultant fragments using tributylphosphine and iodoacetamide to prepare samples in about 2 h. Following simple introduction of a single, unseparated mixture of alkylated fragments into a mass spectrometer, detailed structural information is obtained, covering the entire antibody molecule. 27342663 4 26 theme structural 1068:1077 arg1 information 1079:1089 detailed structural information 1059:1089 detailed structural information 1059:1089 In this study, we coupled IdeS fragmentation and simultaneous reduction and alkylation of the resultant fragments using tributylphosphine and iodoacetamide to prepare samples in about 2 h. Following simple introduction of a single, unseparated mixture of alkylated fragments into a mass spectrometer, detailed structural information is obtained, covering the entire antibody molecule. 27342663 4 27 theme simultaneous 807:818 arg1 reduction 820:828 simultaneous reduction 807:828 simultaneous reduction 807:828 In this study, we coupled IdeS fragmentation and simultaneous reduction and alkylation of the resultant fragments using tributylphosphine and iodoacetamide to prepare samples in about 2 h. Following simple introduction of a single, unseparated mixture of alkylated fragments into a mass spectrometer, detailed structural information is obtained, covering the entire antibody molecule. 27342663 3 28 theme G-degrading 502:512 arg1 enzyme 514:519 the Immunoglobulin G-degrading enzyme 483:519 the Immunoglobulin G-degrading enzyme 483:519 Recent discovery and commercialization of the Immunoglobulin G-degrading enzyme of Streptococcus pyogene (IdeS protease) has facilitated and improved the generation of antibody fragments of suitable size to allow characterization of the structure of the entire antibody molecule via analysis of just a few fragments. 27342663 0 29 theme Structural 0:9 arg1 characterization 11:26 Structural characterization 0:26 Structural characterization of expressed monoclonal antibodies by single sample mass spectral analysis after IdeS proteolysis. 0:125 Structural characterization of expressed monoclonal antibodies by single sample mass spectral analysis after IdeS proteolysis. 27342663 2 30 theme spectral 360:367 arg1 method 392:397 a powerful method 381:397 a powerful method for characterizing monoclonal antibodies 381:438 Mass spectral analysis is a powerful method for characterizing monoclonal antibodies. 27342663 2 30 theme spectral 360:367 arg1 analysis 369:376 Mass spectral analysis 355:376 Mass spectral analysis 355:376 Mass spectral analysis is a powerful method for characterizing monoclonal antibodies. 27342663 1 31 theme post-translational 202:219 arg1 modifications 221:233 post-translational modifications 202:233 post-translational modifications 202:233 Simple and rapid methods for analysis of monoclonal antibody structure and post-translational modifications are increasingly needed due to the explosion of therapeutic monoclonal antibodies and monoclonal antibody applications. 27342663 0 32 theme expressed 31:39 arg1 antibodies 52:61 expressed monoclonal antibodies 31:61 expressed monoclonal antibodies 31:61 Structural characterization of expressed monoclonal antibodies by single sample mass spectral analysis after IdeS proteolysis. 27342663 1 33 theme monoclonal 321:330 arg1 applications 341:352 monoclonal antibody applications 321:352 monoclonal antibody applications 321:352 Simple and rapid methods for analysis of monoclonal antibody structure and post-translational modifications are increasingly needed due to the explosion of therapeutic monoclonal antibodies and monoclonal antibody applications. 27342663 4 34 theme alkylated 1013:1021 arg1 fragments 1023:1031 alkylated fragments 1013:1031 alkylated fragments 1013:1031 In this study, we coupled IdeS fragmentation and simultaneous reduction and alkylation of the resultant fragments using tributylphosphine and iodoacetamide to prepare samples in about 2 h. Following simple introduction of a single, unseparated mixture of alkylated fragments into a mass spectrometer, detailed structural information is obtained, covering the entire antibody molecule. 27342663 2 35 theme Mass 355:358 arg1 method 392:397 a powerful method 381:397 a powerful method for characterizing monoclonal antibodies 381:438 Mass spectral analysis is a powerful method for characterizing monoclonal antibodies. 27342663 2 35 theme Mass 355:358 arg1 analysis 369:376 Mass spectral analysis 355:376 Mass spectral analysis 355:376 Mass spectral analysis is a powerful method for characterizing monoclonal antibodies. 27342663 1 36 theme modifications 221:233 arg1 analysis 156:163 analysis 156:163 analysis of monoclonal antibody structure and post-translational modifications 156:233 Simple and rapid methods for analysis of monoclonal antibody structure and post-translational modifications are increasingly needed due to the explosion of therapeutic monoclonal antibodies and monoclonal antibody applications. 27342663 3 37 theme Recent 441:446 arg1 discovery 448:456 Recent discovery 441:456 Recent discovery 441:456 Recent discovery and commercialization of the Immunoglobulin G-degrading enzyme of Streptococcus pyogene (IdeS protease) has facilitated and improved the generation of antibody fragments of suitable size to allow characterization of the structure of the entire antibody molecule via analysis of just a few fragments. 27342663 1 38 theme antibody 332:339 arg1 applications 341:352 monoclonal antibody applications 321:352 monoclonal antibody applications 321:352 Simple and rapid methods for analysis of monoclonal antibody structure and post-translational modifications are increasingly needed due to the explosion of therapeutic monoclonal antibodies and monoclonal antibody applications. 27342663 4 39 theme resultant 852:860 arg1 fragments 862:870 the resultant fragments 848:870 the resultant fragments using tributylphosphine and iodoacetamide 848:912 In this study, we coupled IdeS fragmentation and simultaneous reduction and alkylation of the resultant fragments using tributylphosphine and iodoacetamide to prepare samples in about 2 h. Following simple introduction of a single, unseparated mixture of alkylated fragments into a mass spectrometer, detailed structural information is obtained, covering the entire antibody molecule. 27342663 5 40 link N-linked 1213:1220 arg1 chain 1254:1258 the heavy chain 1244:1258 the heavy chain 1244:1258 The large majority of the glycoforms present on the single, conserved N-linked glycosylation site of the heavy chain is elucidated, although some of the very low abundance glycoforms are not determined by this protocol. 27342663 5 40 link N-linked 1213:1220 arg1 site 1236:1239 the single, conserved N-linked glycosylation site 1191:1239 the single, conserved N-linked glycosylation site of the heavy chain 1191:1258 The large majority of the glycoforms present on the single, conserved N-linked glycosylation site of the heavy chain is elucidated, although some of the very low abundance glycoforms are not determined by this protocol. 27342663 0 41 theme antibodies 52:61 arg1 characterization 11:26 Structural characterization 0:26 Structural characterization of expressed monoclonal antibodies by single sample mass spectral analysis after IdeS proteolysis. 0:125 Structural characterization of expressed monoclonal antibodies by single sample mass spectral analysis after IdeS proteolysis. 27342663 1 42 theme applications 341:352 arg1 explosion 270:278 the explosion 266:278 the explosion of therapeutic monoclonal antibodies and monoclonal antibody applications 266:352 Simple and rapid methods for analysis of monoclonal antibody structure and post-translational modifications are increasingly needed due to the explosion of therapeutic monoclonal antibodies and monoclonal antibody applications. 27342663 5 43 theme glycoforms 1169:1178 arg1 majority 1153:1160 The large majority 1143:1160 The large majority of the glycoforms present on the single, conserved N-linked glycosylation site of the heavy chain 1143:1258 The large majority of the glycoforms present on the single, conserved N-linked glycosylation site of the heavy chain is elucidated, although some of the very low abundance glycoforms are not determined by this protocol. 27342663 3 44 theme structure 678:686 arg1 characterization 654:669 characterization 654:669 characterization of the structure of the entire antibody molecule 654:718 Recent discovery and commercialization of the Immunoglobulin G-degrading enzyme of Streptococcus pyogene (IdeS protease) has facilitated and improved the generation of antibody fragments of suitable size to allow characterization of the structure of the entire antibody molecule via analysis of just a few fragments. 27342663 3 45 theme enzyme 514:519 arg1 discovery 448:456 Recent discovery 441:456 Recent discovery 441:456 Recent discovery and commercialization of the Immunoglobulin G-degrading enzyme of Streptococcus pyogene (IdeS protease) has facilitated and improved the generation of antibody fragments of suitable size to allow characterization of the structure of the entire antibody molecule via analysis of just a few fragments. 27342663 3 45 theme enzyme 514:519 arg1 commercialization 462:478 commercialization 462:478 commercialization 462:478 Recent discovery and commercialization of the Immunoglobulin G-degrading enzyme of Streptococcus pyogene (IdeS protease) has facilitated and improved the generation of antibody fragments of suitable size to allow characterization of the structure of the entire antibody molecule via analysis of just a few fragments. 27342663 3 46 theme pyogene 538:544 arg1 discovery 448:456 Recent discovery 441:456 Recent discovery 441:456 Recent discovery and commercialization of the Immunoglobulin G-degrading enzyme of Streptococcus pyogene (IdeS protease) has facilitated and improved the generation of antibody fragments of suitable size to allow characterization of the structure of the entire antibody molecule via analysis of just a few fragments. 27342663 3 46 theme pyogene 538:544 arg1 commercialization 462:478 commercialization 462:478 commercialization 462:478 Recent discovery and commercialization of the Immunoglobulin G-degrading enzyme of Streptococcus pyogene (IdeS protease) has facilitated and improved the generation of antibody fragments of suitable size to allow characterization of the structure of the entire antibody molecule via analysis of just a few fragments. 27342663 0 47 theme monoclonal 41:50 arg1 antibodies 52:61 expressed monoclonal antibodies 31:61 expressed monoclonal antibodies 31:61 Structural characterization of expressed monoclonal antibodies by single sample mass spectral analysis after IdeS proteolysis. 27342663 3 48 theme Immunoglobulin 487:500 arg1 enzyme 514:519 the Immunoglobulin G-degrading enzyme 483:519 the Immunoglobulin G-degrading enzyme 483:519 Recent discovery and commercialization of the Immunoglobulin G-degrading enzyme of Streptococcus pyogene (IdeS protease) has facilitated and improved the generation of antibody fragments of suitable size to allow characterization of the structure of the entire antibody molecule via analysis of just a few fragments. 27342663 5 49 theme present 1180:1186 arg1 glycoforms 1169:1178 the glycoforms 1165:1178 the glycoforms present on the single, conserved N-linked glycosylation site of the heavy chain 1165:1258 The large majority of the glycoforms present on the single, conserved N-linked glycosylation site of the heavy chain is elucidated, although some of the very low abundance glycoforms are not determined by this protocol. 27342663 6 50 theme method 1410:1415 arg1 speed 1385:1389 speed 1385:1389 speed 1385:1389 The ease, simplicity, speed, and power of this method make it attractive for analysis of the developmental stages and production batches of therapeutic monoclonal antibodies. 27342663 6 50 theme method 1410:1415 arg1 power 1396:1400 power 1396:1400 power 1396:1400 The ease, simplicity, speed, and power of this method make it attractive for analysis of the developmental stages and production batches of therapeutic monoclonal antibodies. 27342663 6 50 theme method 1410:1415 arg1 simplicity 1373:1382 simplicity 1373:1382 simplicity 1373:1382 The ease, simplicity, speed, and power of this method make it attractive for analysis of the developmental stages and production batches of therapeutic monoclonal antibodies. 27342663 0 51 theme single 66:71 arg1 analysis 94:101 single sample mass spectral analysis 66:101 single sample mass spectral analysis after IdeS proteolysis 66:124 Structural characterization of expressed monoclonal antibodies by single sample mass spectral analysis after IdeS proteolysis. 27342663 4 52 theme mass 1040:1043 arg1 spectrometer 1045:1056 a mass spectrometer 1038:1056 a mass spectrometer 1038:1056 In this study, we coupled IdeS fragmentation and simultaneous reduction and alkylation of the resultant fragments using tributylphosphine and iodoacetamide to prepare samples in about 2 h. Following simple introduction of a single, unseparated mixture of alkylated fragments into a mass spectrometer, detailed structural information is obtained, covering the entire antibody molecule. 27342663 4 53 theme detailed 1059:1066 arg1 information 1079:1089 detailed structural information 1059:1089 detailed structural information 1059:1089 In this study, we coupled IdeS fragmentation and simultaneous reduction and alkylation of the resultant fragments using tributylphosphine and iodoacetamide to prepare samples in about 2 h. Following simple introduction of a single, unseparated mixture of alkylated fragments into a mass spectrometer, detailed structural information is obtained, covering the entire antibody molecule. 27342663 6 54 theme therapeutic 1503:1513 arg1 antibodies 1526:1535 therapeutic monoclonal antibodies 1503:1535 therapeutic monoclonal antibodies 1503:1535 The ease, simplicity, speed, and power of this method make it attractive for analysis of the developmental stages and production batches of therapeutic monoclonal antibodies. 27342663 1 55 theme Simple 127:132 arg1 methods 144:150 Simple and rapid methods 127:150 Simple and rapid methods for analysis of monoclonal antibody structure and post-translational modifications 127:233 Simple and rapid methods for analysis of monoclonal antibody structure and post-translational modifications are increasingly needed due to the explosion of therapeutic monoclonal antibodies and monoclonal antibody applications. 27342663 4 56 theme fragments 1023:1031 arg1 mixture 1002:1008 a single, unseparated mixture 980:1008 a single, unseparated mixture of alkylated fragments 980:1031 In this study, we coupled IdeS fragmentation and simultaneous reduction and alkylation of the resultant fragments using tributylphosphine and iodoacetamide to prepare samples in about 2 h. Following simple introduction of a single, unseparated mixture of alkylated fragments into a mass spectrometer, detailed structural information is obtained, covering the entire antibody molecule. 27342663 5 57 theme chain 1254:1258 arg1 chain 1254:1258 the heavy chain 1244:1258 the heavy chain 1244:1258 The large majority of the glycoforms present on the single, conserved N-linked glycosylation site of the heavy chain is elucidated, although some of the very low abundance glycoforms are not determined by this protocol. 27342663 5 57 theme chain 1254:1258 arg1 site 1236:1239 the single, conserved N-linked glycosylation site 1191:1239 the single, conserved N-linked glycosylation site of the heavy chain 1191:1258 The large majority of the glycoforms present on the single, conserved N-linked glycosylation site of the heavy chain is elucidated, although some of the very low abundance glycoforms are not determined by this protocol. 27342663 4 58 theme single 982:987 arg1 mixture 1002:1008 a single, unseparated mixture 980:1008 a single, unseparated mixture of alkylated fragments 980:1031 In this study, we coupled IdeS fragmentation and simultaneous reduction and alkylation of the resultant fragments using tributylphosphine and iodoacetamide to prepare samples in about 2 h. Following simple introduction of a single, unseparated mixture of alkylated fragments into a mass spectrometer, detailed structural information is obtained, covering the entire antibody molecule. 27342663 3 59 theme fragments 747:755 arg1 analysis 724:731 analysis 724:731 analysis of just a few fragments 724:755 Recent discovery and commercialization of the Immunoglobulin G-degrading enzyme of Streptococcus pyogene (IdeS protease) has facilitated and improved the generation of antibody fragments of suitable size to allow characterization of the structure of the entire antibody molecule via analysis of just a few fragments. 27342663 2 60 theme powerful 383:390 arg1 method 392:397 a powerful method 381:397 a powerful method for characterizing monoclonal antibodies 381:438 Mass spectral analysis is a powerful method for characterizing monoclonal antibodies. 27342663 2 60 theme powerful 383:390 arg1 analysis 369:376 Mass spectral analysis 355:376 Mass spectral analysis 355:376 Mass spectral analysis is a powerful method for characterizing monoclonal antibodies. 27342663 5 61 dep single 1195:1200 arg1 conserved 1203:1211 conserved 1203:1211 conserved 1203:1211 The large majority of the glycoforms present on the single, conserved N-linked glycosylation site of the heavy chain is elucidated, although some of the very low abundance glycoforms are not determined by this protocol. 27342663 4 62 theme mixture 1002:1008 arg1 introduction 964:975 simple introduction 957:975 simple introduction of a single, unseparated mixture of alkylated fragments into a mass spectrometer 957:1056 In this study, we coupled IdeS fragmentation and simultaneous reduction and alkylation of the resultant fragments using tributylphosphine and iodoacetamide to prepare samples in about 2 h. Following simple introduction of a single, unseparated mixture of alkylated fragments into a mass spectrometer, detailed structural information is obtained, covering the entire antibody molecule. 27342663 5 63 theme large 1147:1151 arg1 majority 1153:1160 The large majority 1143:1160 The large majority of the glycoforms present on the single, conserved N-linked glycosylation site of the heavy chain 1143:1258 The large majority of the glycoforms present on the single, conserved N-linked glycosylation site of the heavy chain is elucidated, although some of the very low abundance glycoforms are not determined by this protocol. 27342663 3 64 theme antibody 702:709 arg1 molecule 711:718 the entire antibody molecule 691:718 the entire antibody molecule 691:718 Recent discovery and commercialization of the Immunoglobulin G-degrading enzyme of Streptococcus pyogene (IdeS protease) has facilitated and improved the generation of antibody fragments of suitable size to allow characterization of the structure of the entire antibody molecule via analysis of just a few fragments. 27342663 6 65 theme monoclonal 1515:1524 arg1 antibodies 1526:1535 therapeutic monoclonal antibodies 1503:1535 therapeutic monoclonal antibodies 1503:1535 The ease, simplicity, speed, and power of this method make it attractive for analysis of the developmental stages and production batches of therapeutic monoclonal antibodies. 27342663 1 66 theme rapid 138:142 arg1 methods 144:150 Simple and rapid methods 127:150 Simple and rapid methods for analysis of monoclonal antibody structure and post-translational modifications 127:233 Simple and rapid methods for analysis of monoclonal antibody structure and post-translational modifications are increasingly needed due to the explosion of therapeutic monoclonal antibodies and monoclonal antibody applications. 27342663 3 67 theme size 640:643 arg1 fragments 618:626 antibody fragments 609:626 antibody fragments of suitable size 609:643 Recent discovery and commercialization of the Immunoglobulin G-degrading enzyme of Streptococcus pyogene (IdeS protease) has facilitated and improved the generation of antibody fragments of suitable size to allow characterization of the structure of the entire antibody molecule via analysis of just a few fragments. 27342663 5 68 theme abundance 1305:1313 arg1 glycoforms 1315:1324 the very low abundance glycoforms 1292:1324 the very low abundance glycoforms 1292:1324 The large majority of the glycoforms present on the single, conserved N-linked glycosylation site of the heavy chain is elucidated, although some of the very low abundance glycoforms are not determined by this protocol. 27342663 3 69 theme molecule 711:718 arg1 structure 678:686 the structure 674:686 the structure of the entire antibody molecule 674:718 Recent discovery and commercialization of the Immunoglobulin G-degrading enzyme of Streptococcus pyogene (IdeS protease) has facilitated and improved the generation of antibody fragments of suitable size to allow characterization of the structure of the entire antibody molecule via analysis of just a few fragments. 27342663 4 70 theme IdeS 784:787 arg1 fragmentation 789:801 IdeS fragmentation 784:801 IdeS fragmentation 784:801 In this study, we coupled IdeS fragmentation and simultaneous reduction and alkylation of the resultant fragments using tributylphosphine and iodoacetamide to prepare samples in about 2 h. Following simple introduction of a single, unseparated mixture of alkylated fragments into a mass spectrometer, detailed structural information is obtained, covering the entire antibody molecule. 27342663 6 71 theme batches 1492:1498 arg1 analysis 1440:1447 analysis 1440:1447 analysis of the developmental stages and production batches of therapeutic monoclonal antibodies 1440:1535 The ease, simplicity, speed, and power of this method make it attractive for analysis of the developmental stages and production batches of therapeutic monoclonal antibodies. 27342663 0 72 theme mass 80:83 arg1 analysis 94:101 single sample mass spectral analysis 66:101 single sample mass spectral analysis after IdeS proteolysis 66:124 Structural characterization of expressed monoclonal antibodies by single sample mass spectral analysis after IdeS proteolysis. 27342663 3 73 theme IdeS 547:550 arg1 pyogene 538:544 Streptococcus pyogene 524:544 Streptococcus pyogene (IdeS protease) 524:560 Recent discovery and commercialization of the Immunoglobulin G-degrading enzyme of Streptococcus pyogene (IdeS protease) has facilitated and improved the generation of antibody fragments of suitable size to allow characterization of the structure of the entire antibody molecule via analysis of just a few fragments. 27342663 3 73 theme IdeS 547:550 arg1 protease 552:559 IdeS protease 547:559 IdeS protease 547:559 Recent discovery and commercialization of the Immunoglobulin G-degrading enzyme of Streptococcus pyogene (IdeS protease) has facilitated and improved the generation of antibody fragments of suitable size to allow characterization of the structure of the entire antibody molecule via analysis of just a few fragments. 27342663 6 74 theme developmental 1456:1468 arg1 stages 1470:1475 developmental stages 1456:1475 developmental stages 1456:1475 The ease, simplicity, speed, and power of this method make it attractive for analysis of the developmental stages and production batches of therapeutic monoclonal antibodies. 27342663 3 75 theme Streptococcus 524:536 arg1 pyogene 538:544 Streptococcus pyogene 524:544 Streptococcus pyogene (IdeS protease) 524:560 Recent discovery and commercialization of the Immunoglobulin G-degrading enzyme of Streptococcus pyogene (IdeS protease) has facilitated and improved the generation of antibody fragments of suitable size to allow characterization of the structure of the entire antibody molecule via analysis of just a few fragments. 27342663 3 75 theme Streptococcus 524:536 arg1 protease 552:559 IdeS protease 547:559 IdeS protease 547:559 Recent discovery and commercialization of the Immunoglobulin G-degrading enzyme of Streptococcus pyogene (IdeS protease) has facilitated and improved the generation of antibody fragments of suitable size to allow characterization of the structure of the entire antibody molecule via analysis of just a few fragments. 27342663 0 76 theme sample 73:78 arg1 analysis 94:101 single sample mass spectral analysis 66:101 single sample mass spectral analysis after IdeS proteolysis 66:124 Structural characterization of expressed monoclonal antibodies by single sample mass spectral analysis after IdeS proteolysis. 27342663 5 77 theme N-linked 1213:1220 arg1 chain 1254:1258 the heavy chain 1244:1258 the heavy chain 1244:1258 The large majority of the glycoforms present on the single, conserved N-linked glycosylation site of the heavy chain is elucidated, although some of the very low abundance glycoforms are not determined by this protocol. 27342663 5 77 theme N-linked 1213:1220 arg1 site 1236:1239 the single, conserved N-linked glycosylation site 1191:1239 the single, conserved N-linked glycosylation site of the heavy chain 1191:1258 The large majority of the glycoforms present on the single, conserved N-linked glycosylation site of the heavy chain is elucidated, although some of the very low abundance glycoforms are not determined by this protocol. 27342663 3 78 theme entire 695:700 arg1 molecule 711:718 the entire antibody molecule 691:718 the entire antibody molecule 691:718 Recent discovery and commercialization of the Immunoglobulin G-degrading enzyme of Streptococcus pyogene (IdeS protease) has facilitated and improved the generation of antibody fragments of suitable size to allow characterization of the structure of the entire antibody molecule via analysis of just a few fragments. 27342663 2 79 theme monoclonal 418:427 arg1 antibodies 429:438 monoclonal antibodies 418:438 monoclonal antibodies 418:438 Mass spectral analysis is a powerful method for characterizing monoclonal antibodies. 27342663 5 80 theme heavy 1248:1252 arg1 chain 1254:1258 the heavy chain 1244:1258 the heavy chain 1244:1258 The large majority of the glycoforms present on the single, conserved N-linked glycosylation site of the heavy chain is elucidated, although some of the very low abundance glycoforms are not determined by this protocol. 24501222 7 0 theme important 1093:1101 arg1 site 1125:1128 an important molecular interaction site 1090:1128 an important molecular interaction site on HRG 1090:1135 The structure confirms that the N2 domain, which along with the N1 domain, forms an important molecular interaction site on HRG, possesses a cystatin-like fold composed of a 5-stranded antiparallel β-sheet wrapped around a 5-turn α-helix. 24501222 2 1 theme C-terminal 507:516 arg1 domain 518:523 a C-terminal domain 505:523 a C-terminal domain 505:523 The protein is composed of 2 N-terminal domains (N1 and N2), 2 proline-rich regions (PRR1 and PRR2) that flank a histidine-rich region (HRR), and a C-terminal domain. 24501222 6 2 theme HRG 1004:1006 arg1 domain 972:977 the N2 domain 965:977 the N2 domain of serum-purified rabbit HRG 965:1006 Here, we present a 1.93 Å resolution crystal structure of the N2 domain of serum-purified rabbit HRG. 24501222 6 2 theme HRG 1004:1006 arg1 HRG 1004:1006 serum-purified rabbit HRG 982:1006 serum-purified rabbit HRG 982:1006 Here, we present a 1.93 Å resolution crystal structure of the N2 domain of serum-purified rabbit HRG. 24501222 7 3 theme molecular 1103:1111 arg1 site 1125:1128 an important molecular interaction site 1090:1128 an important molecular interaction site on HRG 1090:1135 The structure confirms that the N2 domain, which along with the N1 domain, forms an important molecular interaction site on HRG, possesses a cystatin-like fold composed of a 5-stranded antiparallel β-sheet wrapped around a 5-turn α-helix. 24501222 7 4 contain possesses 1138:1146 arg2 fold 1164:1167 a cystatin-like fold 1148:1167 a cystatin-like fold composed of a 5-stranded antiparallel β-sheet wrapped around a 5-turn α-helix 1148:1245 The structure confirms that the N2 domain, which along with the N1 domain, forms an important molecular interaction site on HRG, possesses a cystatin-like fold composed of a 5-stranded antiparallel β-sheet wrapped around a 5-turn α-helix. 24501222 7 4 contain possesses 1138:1146 arg1 domain 1044:1049 the N2 domain 1037:1049 the N2 domain 1037:1049 The structure confirms that the N2 domain, which along with the N1 domain, forms an important molecular interaction site on HRG, possesses a cystatin-like fold composed of a 5-stranded antiparallel β-sheet wrapped around a 5-turn α-helix. 24501222 5 5 theme disulphide 830:839 arg1 bond 841:844 a disulphide bond 828:844 a disulphide bond 828:844 However, its release also requires cleavage of a disulphide bond suggesting that its activity is mediated by a redox process. 24501222 0 6 theme disulfide 100:108 arg1 bridge 110:115 an interdomain disulfide bridge 85:115 an interdomain disulfide bridge 85:115 Crystal structure of histidine-rich glycoprotein N2 domain reveals redox activity at an interdomain disulfide bridge: implications for angiogenic regulation. 24501222 4 7 theme plasmin-mediated 700:715 arg1 cleavage 717:724 plasmin-mediated cleavage 700:724 plasmin-mediated cleavage 700:724 It is thought that an HRG fragment containing the HRR, released via plasmin-mediated cleavage, acts as a negative regulator of angiogenesis in vivo. 24501222 8 8 theme glycosylation 1266:1278 arg1 site 1280:1283 A native N-linked glycosylation site 1248:1283 A native N-linked glycosylation site 1248:1283 A native N-linked glycosylation site was identified at Asn184. 24501222 0 9 theme interdomain 88:98 arg1 bridge 110:115 an interdomain disulfide bridge 85:115 an interdomain disulfide bridge 85:115 Crystal structure of histidine-rich glycoprotein N2 domain reveals redox activity at an interdomain disulfide bridge: implications for angiogenic regulation. 24501222 5 10 theme redox 892:896 arg1 process 898:904 a redox process 890:904 a redox process 890:904 However, its release also requires cleavage of a disulphide bond suggesting that its activity is mediated by a redox process. 24501222 1 11 theme important 266:274 arg1 regulator 276:284 an important regulator 263:284 an important regulator of key cardiovascular processes, including angiogenesis and coagulation 263:356 Histidine-rich glycoprotein (HRG) is a plasma protein consisting of 6 distinct functional domains and is an important regulator of key cardiovascular processes, including angiogenesis and coagulation. 24501222 4 12 contain containing 667:676 arg1 fragment 658:665 an HRG fragment 651:665 an HRG fragment containing the HRR, released via plasmin-mediated cleavage, 651:725 It is thought that an HRG fragment containing the HRR, released via plasmin-mediated cleavage, acts as a negative regulator of angiogenesis in vivo. 24501222 4 12 contain containing 667:676 arg1 regulator 746:754 a negative regulator 735:754 a negative regulator of angiogenesis 735:770 It is thought that an HRG fragment containing the HRR, released via plasmin-mediated cleavage, acts as a negative regulator of angiogenesis in vivo. 24501222 4 12 contain containing 667:676 arg2 HRR 682:684 the HRR 678:684 the HRR 678:684 It is thought that an HRG fragment containing the HRR, released via plasmin-mediated cleavage, acts as a negative regulator of angiogenesis in vivo. 24501222 9 13 contain has 1401:1403 arg2 implications 1405:1416 implications 1405:1416 implications for the redox-mediated release of the antiangiogenic cleavage product from HRG 1405:1495 Moreover, the structure reveals the presence of an S-glutathionyl adduct at Cys185, which has implications for the redox-mediated release of the antiangiogenic cleavage product from HRG. 24501222 9 13 contain has 1401:1403 arg1 adduct 1377:1382 an S-glutathionyl adduct 1359:1382 an S-glutathionyl adduct 1359:1382 Moreover, the structure reveals the presence of an S-glutathionyl adduct at Cys185, which has implications for the redox-mediated release of the antiangiogenic cleavage product from HRG. 24501222 6 14 theme domain 972:977 arg1 structure 952:960 a 1.93 Å resolution crystal structure 924:960 a 1.93 Å resolution crystal structure of the N2 domain of serum-purified rabbit HRG 924:1006 Here, we present a 1.93 Å resolution crystal structure of the N2 domain of serum-purified rabbit HRG. 24501222 6 15 theme serum-purified 982:995 arg1 HRG 1004:1006 serum-purified rabbit HRG 982:1006 serum-purified rabbit HRG 982:1006 Here, we present a 1.93 Å resolution crystal structure of the N2 domain of serum-purified rabbit HRG. 24501222 2 16 theme histidine-rich 472:485 arg1 region 487:492 a histidine-rich region 470:492 a histidine-rich region (HRR) 470:498 The protein is composed of 2 N-terminal domains (N1 and N2), 2 proline-rich regions (PRR1 and PRR2) that flank a histidine-rich region (HRR), and a C-terminal domain. 24501222 2 16 theme histidine-rich 472:485 arg1 HRR 495:497 HRR 495:497 HRR 495:497 The protein is composed of 2 N-terminal domains (N1 and N2), 2 proline-rich regions (PRR1 and PRR2) that flank a histidine-rich region (HRR), and a C-terminal domain. 24501222 0 17 theme Crystal 0:6 arg1 structure 8:16 Crystal structure 0:16 Crystal structure of histidine-rich glycoprotein N2 domain 0:57 Crystal structure of histidine-rich glycoprotein N2 domain reveals redox activity at an interdomain disulfide bridge: implications for angiogenic regulation. 24501222 8 18 link N-linked 1257:1264 arg1 site 1280:1283 A native N-linked glycosylation site 1248:1283 A native N-linked glycosylation site 1248:1283 A native N-linked glycosylation site was identified at Asn184. 24501222 9 19 from presence 1347:1354 arg1 Cys185 1387:1392 Cys185 1387:1392 Cys185 1387:1392 Moreover, the structure reveals the presence of an S-glutathionyl adduct at Cys185, which has implications for the redox-mediated release of the antiangiogenic cleavage product from HRG. 24501222 2 20 dep regions 435:441 arg1 PRR1 444:447 PRR1 444:447 PRR1 444:447 The protein is composed of 2 N-terminal domains (N1 and N2), 2 proline-rich regions (PRR1 and PRR2) that flank a histidine-rich region (HRR), and a C-terminal domain. 24501222 2 20 dep regions 435:441 arg1 regions 435:441 2 proline-rich regions 420:441 2 proline-rich regions (PRR1 and PRR2) that flank a histidine-rich region (HRR), and a C-terminal domain 420:523 The protein is composed of 2 N-terminal domains (N1 and N2), 2 proline-rich regions (PRR1 and PRR2) that flank a histidine-rich region (HRR), and a C-terminal domain. 24501222 2 20 dep regions 435:441 arg1 PRR2 453:456 PRR2 453:456 PRR2 453:456 The protein is composed of 2 N-terminal domains (N1 and N2), 2 proline-rich regions (PRR1 and PRR2) that flank a histidine-rich region (HRR), and a C-terminal domain. 24501222 8 21 theme N-linked 1257:1264 arg1 site 1280:1283 A native N-linked glycosylation site 1248:1283 A native N-linked glycosylation site 1248:1283 A native N-linked glycosylation site was identified at Asn184. 24501222 2 22 theme N-terminal 388:397 arg1 domains 399:405 2 N-terminal domains 386:405 2 N-terminal domains (N1 and N2) 386:417 The protein is composed of 2 N-terminal domains (N1 and N2), 2 proline-rich regions (PRR1 and PRR2) that flank a histidine-rich region (HRR), and a C-terminal domain. 24501222 2 22 theme N-terminal 388:397 arg1 regions 435:441 2 proline-rich regions 420:441 2 proline-rich regions (PRR1 and PRR2) that flank a histidine-rich region (HRR), and a C-terminal domain 420:523 The protein is composed of 2 N-terminal domains (N1 and N2), 2 proline-rich regions (PRR1 and PRR2) that flank a histidine-rich region (HRR), and a C-terminal domain. 24501222 2 22 theme N-terminal 388:397 arg1 N2 415:416 N2 415:416 N2 415:416 The protein is composed of 2 N-terminal domains (N1 and N2), 2 proline-rich regions (PRR1 and PRR2) that flank a histidine-rich region (HRR), and a C-terminal domain. 24501222 2 22 theme N-terminal 388:397 arg1 N1 408:409 N1 408:409 N1 408:409 The protein is composed of 2 N-terminal domains (N1 and N2), 2 proline-rich regions (PRR1 and PRR2) that flank a histidine-rich region (HRR), and a C-terminal domain. 24501222 2 23 theme proline-rich 422:433 arg1 domains 399:405 2 N-terminal domains 386:405 2 N-terminal domains (N1 and N2) 386:417 The protein is composed of 2 N-terminal domains (N1 and N2), 2 proline-rich regions (PRR1 and PRR2) that flank a histidine-rich region (HRR), and a C-terminal domain. 24501222 2 23 theme proline-rich 422:433 arg1 PRR1 444:447 PRR1 444:447 PRR1 444:447 The protein is composed of 2 N-terminal domains (N1 and N2), 2 proline-rich regions (PRR1 and PRR2) that flank a histidine-rich region (HRR), and a C-terminal domain. 24501222 2 23 theme proline-rich 422:433 arg1 regions 435:441 2 proline-rich regions 420:441 2 proline-rich regions (PRR1 and PRR2) that flank a histidine-rich region (HRR), and a C-terminal domain 420:523 The protein is composed of 2 N-terminal domains (N1 and N2), 2 proline-rich regions (PRR1 and PRR2) that flank a histidine-rich region (HRR), and a C-terminal domain. 24501222 2 23 theme proline-rich 422:433 arg1 PRR2 453:456 PRR2 453:456 PRR2 453:456 The protein is composed of 2 N-terminal domains (N1 and N2), 2 proline-rich regions (PRR1 and PRR2) that flank a histidine-rich region (HRR), and a C-terminal domain. 24501222 9 24 theme antiangiogenic 1456:1469 arg1 product 1480:1486 the antiangiogenic cleavage product 1452:1486 the antiangiogenic cleavage product 1452:1486 Moreover, the structure reveals the presence of an S-glutathionyl adduct at Cys185, which has implications for the redox-mediated release of the antiangiogenic cleavage product from HRG. 24501222 7 25 from site 1125:1128 arg1 HRG 1133:1135 HRG 1133:1135 HRG 1133:1135 The structure confirms that the N2 domain, which along with the N1 domain, forms an important molecular interaction site on HRG, possesses a cystatin-like fold composed of a 5-stranded antiparallel β-sheet wrapped around a 5-turn α-helix. 24501222 8 26 theme native 1250:1255 arg1 site 1280:1283 A native N-linked glycosylation site 1248:1283 A native N-linked glycosylation site 1248:1283 A native N-linked glycosylation site was identified at Asn184. 24501222 6 27 theme N2 969:970 arg1 domain 972:977 the N2 domain 965:977 the N2 domain of serum-purified rabbit HRG 965:1006 Here, we present a 1.93 Å resolution crystal structure of the N2 domain of serum-purified rabbit HRG. 24501222 6 27 theme N2 969:970 arg1 HRG 1004:1006 serum-purified rabbit HRG 982:1006 serum-purified rabbit HRG 982:1006 Here, we present a 1.93 Å resolution crystal structure of the N2 domain of serum-purified rabbit HRG. 24501222 0 28 theme histidine-rich 21:34 arg1 domain 52:57 histidine-rich glycoprotein N2 domain 21:57 histidine-rich glycoprotein N2 domain 21:57 Crystal structure of histidine-rich glycoprotein N2 domain reveals redox activity at an interdomain disulfide bridge: implications for angiogenic regulation. 24501222 7 29 theme 5-turn 1232:1237 arg1 α-helix 1239:1245 a 5-turn α-helix 1230:1245 a 5-turn α-helix 1230:1245 The structure confirms that the N2 domain, which along with the N1 domain, forms an important molecular interaction site on HRG, possesses a cystatin-like fold composed of a 5-stranded antiparallel β-sheet wrapped around a 5-turn α-helix. 24501222 9 30 from Cys185 1387:1392 arg1 presence 1347:1354 the presence 1343:1354 the presence of an S-glutathionyl adduct at Cys185, which has implications for the redox-mediated release of the antiangiogenic cleavage product from HRG 1343:1495 Moreover, the structure reveals the presence of an S-glutathionyl adduct at Cys185, which has implications for the redox-mediated release of the antiangiogenic cleavage product from HRG. 24501222 9 30 from Cys185 1387:1392 arg1 adduct 1377:1382 an S-glutathionyl adduct 1359:1382 an S-glutathionyl adduct 1359:1382 Moreover, the structure reveals the presence of an S-glutathionyl adduct at Cys185, which has implications for the redox-mediated release of the antiangiogenic cleavage product from HRG. 24501222 9 31 theme product 1480:1486 arg1 release 1441:1447 the redox-mediated release 1422:1447 the redox-mediated release of the antiangiogenic cleavage product from HRG 1422:1495 Moreover, the structure reveals the presence of an S-glutathionyl adduct at Cys185, which has implications for the redox-mediated release of the antiangiogenic cleavage product from HRG. 24501222 3 32 theme structural 535:544 arg1 information 546:556 structural information 535:556 structural information of HRG 535:563 To date, structural information of HRG has largely come from sequence analysis and spectroscopic studies. 24501222 1 33 theme plasma 197:202 arg1 protein 204:210 a plasma protein 195:210 a plasma protein consisting of 6 distinct functional domains 195:254 Histidine-rich glycoprotein (HRG) is a plasma protein consisting of 6 distinct functional domains and is an important regulator of key cardiovascular processes, including angiogenesis and coagulation. 24501222 1 33 theme plasma 197:202 arg1 glycoprotein 173:184 Histidine-rich glycoprotein 158:184 Histidine-rich glycoprotein (HRG) 158:190 Histidine-rich glycoprotein (HRG) is a plasma protein consisting of 6 distinct functional domains and is an important regulator of key cardiovascular processes, including angiogenesis and coagulation. 24501222 9 34 theme cleavage 1471:1478 arg1 product 1480:1486 the antiangiogenic cleavage product 1452:1486 the antiangiogenic cleavage product 1452:1486 Moreover, the structure reveals the presence of an S-glutathionyl adduct at Cys185, which has implications for the redox-mediated release of the antiangiogenic cleavage product from HRG. 24501222 1 35 theme key 289:291 arg1 coagulation 346:356 coagulation 346:356 coagulation 346:356 Histidine-rich glycoprotein (HRG) is a plasma protein consisting of 6 distinct functional domains and is an important regulator of key cardiovascular processes, including angiogenesis and coagulation. 24501222 1 35 theme key 289:291 arg1 processes 308:316 key cardiovascular processes 289:316 key cardiovascular processes 289:316 Histidine-rich glycoprotein (HRG) is a plasma protein consisting of 6 distinct functional domains and is an important regulator of key cardiovascular processes, including angiogenesis and coagulation. 24501222 1 35 theme key 289:291 arg1 angiogenesis 329:340 angiogenesis 329:340 angiogenesis 329:340 Histidine-rich glycoprotein (HRG) is a plasma protein consisting of 6 distinct functional domains and is an important regulator of key cardiovascular processes, including angiogenesis and coagulation. 24501222 3 36 theme sequence 587:594 arg1 analysis 596:603 sequence analysis 587:603 sequence analysis 587:603 To date, structural information of HRG has largely come from sequence analysis and spectroscopic studies. 24501222 6 37 theme rabbit 997:1002 arg1 HRG 1004:1006 serum-purified rabbit HRG 982:1006 serum-purified rabbit HRG 982:1006 Here, we present a 1.93 Å resolution crystal structure of the N2 domain of serum-purified rabbit HRG. 24501222 9 38 from HRG 1493:1495 arg1 release 1441:1447 the redox-mediated release 1422:1447 the redox-mediated release of the antiangiogenic cleavage product from HRG 1422:1495 Moreover, the structure reveals the presence of an S-glutathionyl adduct at Cys185, which has implications for the redox-mediated release of the antiangiogenic cleavage product from HRG. 24501222 7 39 theme antiparallel 1194:1205 arg1 β-sheet 1207:1213 a 5-stranded antiparallel β-sheet 1181:1213 a 5-stranded antiparallel β-sheet wrapped around a 5-turn α-helix 1181:1245 The structure confirms that the N2 domain, which along with the N1 domain, forms an important molecular interaction site on HRG, possesses a cystatin-like fold composed of a 5-stranded antiparallel β-sheet wrapped around a 5-turn α-helix. 24501222 0 40 theme N2 49:50 arg1 domain 52:57 histidine-rich glycoprotein N2 domain 21:57 histidine-rich glycoprotein N2 domain 21:57 Crystal structure of histidine-rich glycoprotein N2 domain reveals redox activity at an interdomain disulfide bridge: implications for angiogenic regulation. 24501222 1 41 theme cardiovascular 293:306 arg1 coagulation 346:356 coagulation 346:356 coagulation 346:356 Histidine-rich glycoprotein (HRG) is a plasma protein consisting of 6 distinct functional domains and is an important regulator of key cardiovascular processes, including angiogenesis and coagulation. 24501222 1 41 theme cardiovascular 293:306 arg1 processes 308:316 key cardiovascular processes 289:316 key cardiovascular processes 289:316 Histidine-rich glycoprotein (HRG) is a plasma protein consisting of 6 distinct functional domains and is an important regulator of key cardiovascular processes, including angiogenesis and coagulation. 24501222 1 41 theme cardiovascular 293:306 arg1 angiogenesis 329:340 angiogenesis 329:340 angiogenesis 329:340 Histidine-rich glycoprotein (HRG) is a plasma protein consisting of 6 distinct functional domains and is an important regulator of key cardiovascular processes, including angiogenesis and coagulation. 24501222 7 42 theme N1 1073:1074 arg1 domain 1076:1081 the N1 domain 1069:1081 the N1 domain 1069:1081 The structure confirms that the N2 domain, which along with the N1 domain, forms an important molecular interaction site on HRG, possesses a cystatin-like fold composed of a 5-stranded antiparallel β-sheet wrapped around a 5-turn α-helix. 24501222 0 43 dep reveals 59:65 arg1 implications 118:129 implications 118:129 implications for angiogenic regulation 118:155 Crystal structure of histidine-rich glycoprotein N2 domain reveals redox activity at an interdomain disulfide bridge: implications for angiogenic regulation. 24501222 9 44 theme S-glutathionyl 1362:1375 arg1 adduct 1377:1382 an S-glutathionyl adduct 1359:1382 an S-glutathionyl adduct 1359:1382 Moreover, the structure reveals the presence of an S-glutathionyl adduct at Cys185, which has implications for the redox-mediated release of the antiangiogenic cleavage product from HRG. 24501222 0 45 theme glycoprotein 36:47 arg1 domain 52:57 histidine-rich glycoprotein N2 domain 21:57 histidine-rich glycoprotein N2 domain 21:57 Crystal structure of histidine-rich glycoprotein N2 domain reveals redox activity at an interdomain disulfide bridge: implications for angiogenic regulation. 24501222 1 46 theme processes 308:316 arg1 protein 204:210 a plasma protein 195:210 a plasma protein consisting of 6 distinct functional domains 195:254 Histidine-rich glycoprotein (HRG) is a plasma protein consisting of 6 distinct functional domains and is an important regulator of key cardiovascular processes, including angiogenesis and coagulation. 24501222 1 46 theme processes 308:316 arg1 regulator 276:284 an important regulator 263:284 an important regulator of key cardiovascular processes, including angiogenesis and coagulation 263:356 Histidine-rich glycoprotein (HRG) is a plasma protein consisting of 6 distinct functional domains and is an important regulator of key cardiovascular processes, including angiogenesis and coagulation. 24501222 1 46 theme processes 308:316 arg1 glycoprotein 173:184 Histidine-rich glycoprotein 158:184 Histidine-rich glycoprotein (HRG) 158:190 Histidine-rich glycoprotein (HRG) is a plasma protein consisting of 6 distinct functional domains and is an important regulator of key cardiovascular processes, including angiogenesis and coagulation. 24501222 0 47 theme angiogenic 135:144 arg1 regulation 146:155 angiogenic regulation 135:155 angiogenic regulation 135:155 Crystal structure of histidine-rich glycoprotein N2 domain reveals redox activity at an interdomain disulfide bridge: implications for angiogenic regulation. 24501222 9 48 theme adduct 1377:1382 arg1 presence 1347:1354 the presence 1343:1354 the presence of an S-glutathionyl adduct at Cys185, which has implications for the redox-mediated release of the antiangiogenic cleavage product from HRG 1343:1495 Moreover, the structure reveals the presence of an S-glutathionyl adduct at Cys185, which has implications for the redox-mediated release of the antiangiogenic cleavage product from HRG. 24501222 6 49 theme crystal 944:950 arg1 structure 952:960 a 1.93 Å resolution crystal structure 924:960 a 1.93 Å resolution crystal structure of the N2 domain of serum-purified rabbit HRG 924:1006 Here, we present a 1.93 Å resolution crystal structure of the N2 domain of serum-purified rabbit HRG. 24501222 7 50 theme N2 1041:1042 arg1 domain 1044:1049 the N2 domain 1037:1049 the N2 domain 1037:1049 The structure confirms that the N2 domain, which along with the N1 domain, forms an important molecular interaction site on HRG, possesses a cystatin-like fold composed of a 5-stranded antiparallel β-sheet wrapped around a 5-turn α-helix. 24501222 4 51 theme HRG 654:656 arg1 fragment 658:665 an HRG fragment 651:665 an HRG fragment containing the HRR, released via plasmin-mediated cleavage, 651:725 It is thought that an HRG fragment containing the HRR, released via plasmin-mediated cleavage, acts as a negative regulator of angiogenesis in vivo. 24501222 4 51 theme HRG 654:656 arg1 regulator 746:754 a negative regulator 735:754 a negative regulator of angiogenesis 735:770 It is thought that an HRG fragment containing the HRR, released via plasmin-mediated cleavage, acts as a negative regulator of angiogenesis in vivo. 24501222 0 52 theme domain 52:57 arg1 structure 8:16 Crystal structure 0:16 Crystal structure of histidine-rich glycoprotein N2 domain 0:57 Crystal structure of histidine-rich glycoprotein N2 domain reveals redox activity at an interdomain disulfide bridge: implications for angiogenic regulation. 24501222 8 53 gly glycosylation 1266:1278 arg2 site 1280:1283 A native N-linked glycosylation site 1248:1283 A native N-linked glycosylation site 1248:1283 A native N-linked glycosylation site was identified at Asn184. 24501222 4 54 theme angiogenesis 759:770 arg1 fragment 658:665 an HRG fragment 651:665 an HRG fragment containing the HRR, released via plasmin-mediated cleavage, 651:725 It is thought that an HRG fragment containing the HRR, released via plasmin-mediated cleavage, acts as a negative regulator of angiogenesis in vivo. 24501222 4 54 theme angiogenesis 759:770 arg1 regulator 746:754 a negative regulator 735:754 a negative regulator of angiogenesis 735:770 It is thought that an HRG fragment containing the HRR, released via plasmin-mediated cleavage, acts as a negative regulator of angiogenesis in vivo. 24501222 0 55 gly glycoprotein 36:47 arg1 glycoprotein 36:47 histidine-rich glycoprotein N2 domain 21:57 histidine-rich glycoprotein N2 domain 21:57 Crystal structure of histidine-rich glycoprotein N2 domain reveals redox activity at an interdomain disulfide bridge: implications for angiogenic regulation. 24501222 6 56 theme Å 931:931 arg1 structure 952:960 a 1.93 Å resolution crystal structure 924:960 a 1.93 Å resolution crystal structure of the N2 domain of serum-purified rabbit HRG 924:1006 Here, we present a 1.93 Å resolution crystal structure of the N2 domain of serum-purified rabbit HRG. 24501222 6 57 theme resolution 933:942 arg1 structure 952:960 a 1.93 Å resolution crystal structure 924:960 a 1.93 Å resolution crystal structure of the N2 domain of serum-purified rabbit HRG 924:1006 Here, we present a 1.93 Å resolution crystal structure of the N2 domain of serum-purified rabbit HRG. 24501222 1 58 gly glycoprotein 173:184 arg1 protein 204:210 a plasma protein 195:210 a plasma protein consisting of 6 distinct functional domains 195:254 Histidine-rich glycoprotein (HRG) is a plasma protein consisting of 6 distinct functional domains and is an important regulator of key cardiovascular processes, including angiogenesis and coagulation. 24501222 1 58 gly glycoprotein 173:184 arg1 HRG 187:189 HRG 187:189 HRG 187:189 Histidine-rich glycoprotein (HRG) is a plasma protein consisting of 6 distinct functional domains and is an important regulator of key cardiovascular processes, including angiogenesis and coagulation. 24501222 1 58 gly glycoprotein 173:184 arg1 glycoprotein 173:184 Histidine-rich glycoprotein 158:184 Histidine-rich glycoprotein (HRG) 158:190 Histidine-rich glycoprotein (HRG) is a plasma protein consisting of 6 distinct functional domains and is an important regulator of key cardiovascular processes, including angiogenesis and coagulation. 24501222 5 59 theme bond 841:844 arg1 cleavage 816:823 cleavage 816:823 cleavage of a disulphide bond 816:844 However, its release also requires cleavage of a disulphide bond suggesting that its activity is mediated by a redox process. 24501222 9 60 theme redox-mediated 1426:1439 arg1 release 1441:1447 the redox-mediated release 1422:1447 the redox-mediated release of the antiangiogenic cleavage product from HRG 1422:1495 Moreover, the structure reveals the presence of an S-glutathionyl adduct at Cys185, which has implications for the redox-mediated release of the antiangiogenic cleavage product from HRG. 24501222 7 61 theme cystatin-like 1150:1162 arg1 fold 1164:1167 a cystatin-like fold 1148:1167 a cystatin-like fold composed of a 5-stranded antiparallel β-sheet wrapped around a 5-turn α-helix 1148:1245 The structure confirms that the N2 domain, which along with the N1 domain, forms an important molecular interaction site on HRG, possesses a cystatin-like fold composed of a 5-stranded antiparallel β-sheet wrapped around a 5-turn α-helix. 24501222 1 62 theme distinct 228:235 arg1 domains 248:254 6 distinct functional domains 226:254 6 distinct functional domains 226:254 Histidine-rich glycoprotein (HRG) is a plasma protein consisting of 6 distinct functional domains and is an important regulator of key cardiovascular processes, including angiogenesis and coagulation. 24501222 7 63 theme interaction 1113:1123 arg1 site 1125:1128 an important molecular interaction site 1090:1128 an important molecular interaction site on HRG 1090:1135 The structure confirms that the N2 domain, which along with the N1 domain, forms an important molecular interaction site on HRG, possesses a cystatin-like fold composed of a 5-stranded antiparallel β-sheet wrapped around a 5-turn α-helix. 24501222 3 64 theme spectroscopic 609:621 arg1 studies 623:629 spectroscopic studies 609:629 spectroscopic studies 609:629 To date, structural information of HRG has largely come from sequence analysis and spectroscopic studies. 24501222 4 65 theme negative 737:744 arg1 fragment 658:665 an HRG fragment 651:665 an HRG fragment containing the HRR, released via plasmin-mediated cleavage, 651:725 It is thought that an HRG fragment containing the HRR, released via plasmin-mediated cleavage, acts as a negative regulator of angiogenesis in vivo. 24501222 4 65 theme negative 737:744 arg1 regulator 746:754 a negative regulator 735:754 a negative regulator of angiogenesis 735:770 It is thought that an HRG fragment containing the HRR, released via plasmin-mediated cleavage, acts as a negative regulator of angiogenesis in vivo. 24501222 7 66 theme 5-stranded 1183:1192 arg1 β-sheet 1207:1213 a 5-stranded antiparallel β-sheet 1181:1213 a 5-stranded antiparallel β-sheet wrapped around a 5-turn α-helix 1181:1245 The structure confirms that the N2 domain, which along with the N1 domain, forms an important molecular interaction site on HRG, possesses a cystatin-like fold composed of a 5-stranded antiparallel β-sheet wrapped around a 5-turn α-helix. 24501222 1 67 theme functional 237:246 arg1 domains 248:254 6 distinct functional domains 226:254 6 distinct functional domains 226:254 Histidine-rich glycoprotein (HRG) is a plasma protein consisting of 6 distinct functional domains and is an important regulator of key cardiovascular processes, including angiogenesis and coagulation. 24501222 0 68 theme redox 67:71 arg1 activity 73:80 redox activity 67:80 redox activity 67:80 Crystal structure of histidine-rich glycoprotein N2 domain reveals redox activity at an interdomain disulfide bridge: implications for angiogenic regulation. 24501222 3 69 theme HRG 561:563 arg1 information 546:556 structural information 535:556 structural information of HRG 535:563 To date, structural information of HRG has largely come from sequence analysis and spectroscopic studies. 24501222 1 70 theme Histidine-rich 158:171 arg1 protein 204:210 a plasma protein 195:210 a plasma protein consisting of 6 distinct functional domains 195:254 Histidine-rich glycoprotein (HRG) is a plasma protein consisting of 6 distinct functional domains and is an important regulator of key cardiovascular processes, including angiogenesis and coagulation. 24501222 1 70 theme Histidine-rich 158:171 arg1 HRG 187:189 HRG 187:189 HRG 187:189 Histidine-rich glycoprotein (HRG) is a plasma protein consisting of 6 distinct functional domains and is an important regulator of key cardiovascular processes, including angiogenesis and coagulation. 24501222 1 70 theme Histidine-rich 158:171 arg1 glycoprotein 173:184 Histidine-rich glycoprotein 158:184 Histidine-rich glycoprotein (HRG) 158:190 Histidine-rich glycoprotein (HRG) is a plasma protein consisting of 6 distinct functional domains and is an important regulator of key cardiovascular processes, including angiogenesis and coagulation. 26837192 8 0 theme V3 1447:1448 arg1 mutations 1450:1458 the observed V3 mutations 1434:1458 the observed V3 mutations 1434:1458 We demonstrate that the observed V3 mutations confer neutralization resistance in other virus strains through both gain-of-function and escape studies. 26837192 4 1 theme N332 812:815 arg1 absence 801:807 the absence 797:807 the absence of N332 797:815 We have recently shown that this bnAb family consists of two distinct antibody classes that can bind alternate arrangements of glycans in the mannose-patch in the absence of N332 thereby limiting viral escape. 26837192 8 2 theme other 1496:1500 arg1 strains 1508:1514 other virus strains 1496:1514 other virus strains 1496:1514 We demonstrate that the observed V3 mutations confer neutralization resistance in other virus strains through both gain-of-function and escape studies. 26837192 3 3 theme N-linked 507:514 arg1 glycans 516:522 at least two N-linked glycans 494:522 at least two N-linked glycans 494:522 The overlapping epitopes recognized by this family are intricate and neutralization requires interaction with at least two N-linked glycans (N332/N334, N295 or N301) in addition to backbone-mediated contact with the (323)IGDIR(327) motif of the V3 loop. 26837192 6 4 gly glycosylation 1122:1134 arg2 sites 1136:1140 repositioning critical N-linked glycosylation sites 1090:1140 repositioning critical N-linked glycosylation sites 1090:1140 RESULTS: Using an escape virus isolated from the PGT125-131 donor as a guide, we show that mutating both the V3 core protein epitope and repositioning critical N-linked glycosylation sites are required to restore neutralization sensitivity. 26837192 8 5 theme neutralization 1467:1480 arg1 resistance 1482:1491 neutralization resistance 1467:1491 neutralization resistance in other virus strains 1467:1514 We demonstrate that the observed V3 mutations confer neutralization resistance in other virus strains through both gain-of-function and escape studies. 26837192 1 6 theme desirable 252:260 arg1 targets 262:268 desirable targets 252:268 desirable targets for vaccine design 252:287 BACKGROUND: Broadly neutralizing antibodies (bnAbs) directed against the mannose-patch on the HIV envelope glycoprotein gp120 have several features that make them desirable targets for vaccine design. 26837192 0 7 from Mechanisms 0:9 arg1 family 37:42 the PGT128 family 26:42 the PGT128 family of anti-HIV 26:54 Mechanisms of escape from the PGT128 family of anti-HIV broadly neutralizing antibodies. 26837192 7 8 theme PGT125-131 1320:1329 arg1 family 1331:1336 the PGT125-131 family 1316:1336 the PGT125-131 family 1316:1336 Interestingly, neutralization sensitivity could be restored via different routes for the two distinct bnAb classes within the PGT125-131 family, which may have been important in generating the divergence in recognition. 26837192 7 8 theme PGT125-131 1320:1329 arg1 important 1359:1367 important 1359:1367 important 1359:1367 Interestingly, neutralization sensitivity could be restored via different routes for the two distinct bnAb classes within the PGT125-131 family, which may have been important in generating the divergence in recognition. 26837192 4 9 theme antibody 708:715 arg1 classes 717:723 two distinct antibody classes 695:723 two distinct antibody classes that can bind alternate arrangements of glycans in the mannose-patch in the absence of N332 thereby limiting viral escape 695:845 We have recently shown that this bnAb family consists of two distinct antibody classes that can bind alternate arrangements of glycans in the mannose-patch in the absence of N332 thereby limiting viral escape. 26837192 1 10 theme Broadly 101:107 arg1 bnAbs 134:138 bnAbs 134:138 bnAbs 134:138 BACKGROUND: Broadly neutralizing antibodies (bnAbs) directed against the mannose-patch on the HIV envelope glycoprotein gp120 have several features that make them desirable targets for vaccine design. 26837192 1 10 theme Broadly 101:107 arg1 antibodies 122:131 Broadly neutralizing antibodies 101:131 Broadly neutralizing antibodies (bnAbs) directed against the mannose-patch on the HIV envelope glycoprotein gp120 101:213 BACKGROUND: Broadly neutralizing antibodies (bnAbs) directed against the mannose-patch on the HIV envelope glycoprotein gp120 have several features that make them desirable targets for vaccine design. 26837192 3 11 with contact 583:589 arg1 motif 616:620 the (323)IGDIR(327) motif 596:620 the (323)IGDIR(327) motif of the V3 loop 596:635 The overlapping epitopes recognized by this family are intricate and neutralization requires interaction with at least two N-linked glycans (N332/N334, N295 or N301) in addition to backbone-mediated contact with the (323)IGDIR(327) motif of the V3 loop. 26837192 6 12 theme core 1065:1068 arg1 epitope 1078:1084 the V3 core protein epitope 1058:1084 the V3 core protein epitope 1058:1084 RESULTS: Using an escape virus isolated from the PGT125-131 donor as a guide, we show that mutating both the V3 core protein epitope and repositioning critical N-linked glycosylation sites are required to restore neutralization sensitivity. 26837192 6 13 theme repositioning 1090:1102 arg1 sites 1136:1140 repositioning critical N-linked glycosylation sites 1090:1140 repositioning critical N-linked glycosylation sites 1090:1140 RESULTS: Using an escape virus isolated from the PGT125-131 donor as a guide, we show that mutating both the V3 core protein epitope and repositioning critical N-linked glycosylation sites are required to restore neutralization sensitivity. 26837192 9 14 theme promiscuous 1633:1643 arg1 binding 1645:1651 promiscuous binding 1633:1651 promiscuous binding to glycans within the mannose-patch 1633:1687 Furthermore, we show that the V3 loop is important in facilitating promiscuous binding to glycans within the mannose-patch. 26837192 4 15 theme distinct 699:706 arg1 classes 717:723 two distinct antibody classes 695:723 two distinct antibody classes that can bind alternate arrangements of glycans in the mannose-patch in the absence of N332 thereby limiting viral escape 695:845 We have recently shown that this bnAb family consists of two distinct antibody classes that can bind alternate arrangements of glycans in the mannose-patch in the absence of N332 thereby limiting viral escape. 26837192 0 16 from family 37:42 arg1 escape 14:19 escape 14:19 escape from the PGT128 family of anti-HIV 14:54 Mechanisms of escape from the PGT128 family of anti-HIV broadly neutralizing antibodies. 26837192 0 16 from family 37:42 arg1 Mechanisms 0:9 Mechanisms 0:9 Mechanisms of escape from the PGT128 family of anti-HIV 0:54 Mechanisms of escape from the PGT128 family of anti-HIV broadly neutralizing antibodies. 26837192 1 17 gly glycoprotein 196:207 arg1 glycoprotein 196:207 the HIV envelope glycoprotein gp120 179:213 the HIV envelope glycoprotein gp120 179:213 BACKGROUND: Broadly neutralizing antibodies (bnAbs) directed against the mannose-patch on the HIV envelope glycoprotein gp120 have several features that make them desirable targets for vaccine design. 26837192 7 18 theme bnAb 1296:1299 arg1 classes 1301:1307 the two distinct bnAb classes 1279:1307 the two distinct bnAb classes within the PGT125-131 family, which may have been important in generating the divergence in recognition 1279:1411 Interestingly, neutralization sensitivity could be restored via different routes for the two distinct bnAb classes within the PGT125-131 family, which may have been important in generating the divergence in recognition. 26837192 10 19 theme immunogens 1771:1780 arg1 design 1761:1766 the design 1757:1766 the design of immunogens aimed at inducing broad and potent bnAbs that can bind promiscuously to the mannose-patch 1757:1870 CONCLUSIONS: These data highlight the importance of the V3 loop in the design of immunogens aimed at inducing broad and potent bnAbs that can bind promiscuously to the mannose-patch. 26837192 8 20 theme virus 1502:1506 arg1 strains 1508:1514 other virus strains 1496:1514 other virus strains 1496:1514 We demonstrate that the observed V3 mutations confer neutralization resistance in other virus strains through both gain-of-function and escape studies. 26837192 3 21 dep contact 583:589 arg1 addition 553:560 addition 553:560 addition 553:560 The overlapping epitopes recognized by this family are intricate and neutralization requires interaction with at least two N-linked glycans (N332/N334, N295 or N301) in addition to backbone-mediated contact with the (323)IGDIR(327) motif of the V3 loop. 26837192 5 22 theme bnAb 940:943 arg1 family 945:950 the PGT125-131 bnAb family 925:950 the PGT125-131 bnAb family 925:950 This led us to further investigate viral resistance and escape mechanisms to the PGT125-131 bnAb family. 26837192 4 23 from mannose-patch 780:792 arg1 absence 801:807 the absence 797:807 the absence of N332 797:815 We have recently shown that this bnAb family consists of two distinct antibody classes that can bind alternate arrangements of glycans in the mannose-patch in the absence of N332 thereby limiting viral escape. 26837192 10 24 theme loop 1749:1752 arg1 importance 1728:1737 the importance 1724:1737 the importance of the V3 loop in the design of immunogens aimed at inducing broad and potent bnAbs that can bind promiscuously to the mannose-patch 1724:1870 CONCLUSIONS: These data highlight the importance of the V3 loop in the design of immunogens aimed at inducing broad and potent bnAbs that can bind promiscuously to the mannose-patch. 26837192 6 25 theme protein 1070:1076 arg1 epitope 1078:1084 the V3 core protein epitope 1058:1084 the V3 core protein epitope 1058:1084 RESULTS: Using an escape virus isolated from the PGT125-131 donor as a guide, we show that mutating both the V3 core protein epitope and repositioning critical N-linked glycosylation sites are required to restore neutralization sensitivity. 26837192 6 26 theme PGT125-131 1002:1011 arg1 donor 1013:1017 the PGT125-131 donor 998:1017 the PGT125-131 donor 998:1017 RESULTS: Using an escape virus isolated from the PGT125-131 donor as a guide, we show that mutating both the V3 core protein epitope and repositioning critical N-linked glycosylation sites are required to restore neutralization sensitivity. 26837192 1 27 theme vaccine 274:280 arg1 design 282:287 vaccine design 274:287 vaccine design 274:287 BACKGROUND: Broadly neutralizing antibodies (bnAbs) directed against the mannose-patch on the HIV envelope glycoprotein gp120 have several features that make them desirable targets for vaccine design. 26837192 3 28 theme V3 629:630 arg1 loop 632:635 the V3 loop 625:635 the V3 loop 625:635 The overlapping epitopes recognized by this family are intricate and neutralization requires interaction with at least two N-linked glycans (N332/N334, N295 or N301) in addition to backbone-mediated contact with the (323)IGDIR(327) motif of the V3 loop. 26837192 1 29 theme HIV 183:185 arg1 gp120 209:213 the HIV envelope glycoprotein gp120 179:213 the HIV envelope glycoprotein gp120 179:213 BACKGROUND: Broadly neutralizing antibodies (bnAbs) directed against the mannose-patch on the HIV envelope glycoprotein gp120 have several features that make them desirable targets for vaccine design. 26837192 6 30 theme glycosylation 1122:1134 arg1 sites 1136:1140 repositioning critical N-linked glycosylation sites 1090:1140 repositioning critical N-linked glycosylation sites 1090:1140 RESULTS: Using an escape virus isolated from the PGT125-131 donor as a guide, we show that mutating both the V3 core protein epitope and repositioning critical N-linked glycosylation sites are required to restore neutralization sensitivity. 26837192 3 31 link N-linked 507:514 arg1 glycans 516:522 at least two N-linked glycans 494:522 at least two N-linked glycans 494:522 The overlapping epitopes recognized by this family are intricate and neutralization requires interaction with at least two N-linked glycans (N332/N334, N295 or N301) in addition to backbone-mediated contact with the (323)IGDIR(327) motif of the V3 loop. 26837192 2 32 theme bnAb 305:308 arg1 family 310:315 The PGT125-131 bnAb family 290:315 The PGT125-131 bnAb family 290:315 The PGT125-131 bnAb family is of particular interest due to its superior breadth and potency. 26837192 6 33 theme neutralization 1166:1179 arg1 sensitivity 1181:1191 neutralization sensitivity 1166:1191 neutralization sensitivity 1166:1191 RESULTS: Using an escape virus isolated from the PGT125-131 donor as a guide, we show that mutating both the V3 core protein epitope and repositioning critical N-linked glycosylation sites are required to restore neutralization sensitivity. 26837192 1 34 theme envelope 187:194 arg1 gp120 209:213 the HIV envelope glycoprotein gp120 179:213 the HIV envelope glycoprotein gp120 179:213 BACKGROUND: Broadly neutralizing antibodies (bnAbs) directed against the mannose-patch on the HIV envelope glycoprotein gp120 have several features that make them desirable targets for vaccine design. 26837192 0 35 theme escape 14:19 arg1 Mechanisms 0:9 Mechanisms 0:9 Mechanisms of escape from the PGT128 family of anti-HIV 0:54 Mechanisms of escape from the PGT128 family of anti-HIV broadly neutralizing antibodies. 26837192 5 36 theme viral 883:887 arg1 mechanisms 911:920 viral resistance and escape mechanisms 883:920 viral resistance and escape mechanisms 883:920 This led us to further investigate viral resistance and escape mechanisms to the PGT125-131 bnAb family. 26837192 6 37 theme critical 1104:1111 arg1 sites 1136:1140 repositioning critical N-linked glycosylation sites 1090:1140 repositioning critical N-linked glycosylation sites 1090:1140 RESULTS: Using an escape virus isolated from the PGT125-131 donor as a guide, we show that mutating both the V3 core protein epitope and repositioning critical N-linked glycosylation sites are required to restore neutralization sensitivity. 26837192 2 38 theme PGT125-131 294:303 arg1 family 310:315 The PGT125-131 bnAb family 290:315 The PGT125-131 bnAb family 290:315 The PGT125-131 bnAb family is of particular interest due to its superior breadth and potency. 26837192 1 39 theme glycoprotein 196:207 arg1 gp120 209:213 the HIV envelope glycoprotein gp120 179:213 the HIV envelope glycoprotein gp120 179:213 BACKGROUND: Broadly neutralizing antibodies (bnAbs) directed against the mannose-patch on the HIV envelope glycoprotein gp120 have several features that make them desirable targets for vaccine design. 26837192 0 40 theme PGT128 30:35 arg1 family 37:42 the PGT128 family 26:42 the PGT128 family of anti-HIV 26:54 Mechanisms of escape from the PGT128 family of anti-HIV broadly neutralizing antibodies. 26837192 5 41 theme escape 904:909 arg1 mechanisms 911:920 viral resistance and escape mechanisms 883:920 viral resistance and escape mechanisms 883:920 This led us to further investigate viral resistance and escape mechanisms to the PGT125-131 bnAb family. 26837192 10 42 theme broad 1800:1804 arg1 bnAbs 1817:1821 broad and potent bnAbs 1800:1821 broad and potent bnAbs that can bind promiscuously to the mannose-patch 1800:1870 CONCLUSIONS: These data highlight the importance of the V3 loop in the design of immunogens aimed at inducing broad and potent bnAbs that can bind promiscuously to the mannose-patch. 26837192 4 43 theme glycans 765:771 arg1 arrangements 749:760 alternate arrangements 739:760 alternate arrangements of glycans 739:771 We have recently shown that this bnAb family consists of two distinct antibody classes that can bind alternate arrangements of glycans in the mannose-patch in the absence of N332 thereby limiting viral escape. 26837192 10 44 from importance 1728:1737 arg1 design 1761:1766 the design 1757:1766 the design of immunogens aimed at inducing broad and potent bnAbs that can bind promiscuously to the mannose-patch 1757:1870 CONCLUSIONS: These data highlight the importance of the V3 loop in the design of immunogens aimed at inducing broad and potent bnAbs that can bind promiscuously to the mannose-patch. 26837192 9 45 theme V3 1596:1597 arg1 important 1607:1615 important 1607:1615 important 1607:1615 Furthermore, we show that the V3 loop is important in facilitating promiscuous binding to glycans within the mannose-patch. 26837192 9 45 theme V3 1596:1597 arg1 loop 1599:1602 the V3 loop 1592:1602 the V3 loop 1592:1602 Furthermore, we show that the V3 loop is important in facilitating promiscuous binding to glycans within the mannose-patch. 26837192 8 46 theme escape 1550:1555 arg1 studies 1557:1563 escape studies 1550:1563 escape studies 1550:1563 We demonstrate that the observed V3 mutations confer neutralization resistance in other virus strains through both gain-of-function and escape studies. 26837192 3 47 with interaction 477:487 arg1 glycans 516:522 at least two N-linked glycans 494:522 at least two N-linked glycans 494:522 The overlapping epitopes recognized by this family are intricate and neutralization requires interaction with at least two N-linked glycans (N332/N334, N295 or N301) in addition to backbone-mediated contact with the (323)IGDIR(327) motif of the V3 loop. 26837192 10 48 theme potent 1810:1815 arg1 bnAbs 1817:1821 broad and potent bnAbs 1800:1821 broad and potent bnAbs that can bind promiscuously to the mannose-patch 1800:1870 CONCLUSIONS: These data highlight the importance of the V3 loop in the design of immunogens aimed at inducing broad and potent bnAbs that can bind promiscuously to the mannose-patch. 26837192 6 49 theme escape 971:976 arg1 virus 978:982 an escape virus 968:982 an escape virus isolated from the PGT125-131 donor 968:1017 RESULTS: Using an escape virus isolated from the PGT125-131 donor as a guide, we show that mutating both the V3 core protein epitope and repositioning critical N-linked glycosylation sites are required to restore neutralization sensitivity. 26837192 6 49 theme escape 971:976 arg1 guide 1024:1028 a guide 1022:1028 a guide 1022:1028 RESULTS: Using an escape virus isolated from the PGT125-131 donor as a guide, we show that mutating both the V3 core protein epitope and repositioning critical N-linked glycosylation sites are required to restore neutralization sensitivity. 26837192 3 50 theme overlapping 388:398 arg1 epitopes 400:407 The overlapping epitopes 384:407 The overlapping epitopes recognized by this family 384:433 The overlapping epitopes recognized by this family are intricate and neutralization requires interaction with at least two N-linked glycans (N332/N334, N295 or N301) in addition to backbone-mediated contact with the (323)IGDIR(327) motif of the V3 loop. 26837192 3 50 theme overlapping 388:398 arg1 intricate 439:447 intricate 439:447 intricate 439:447 The overlapping epitopes recognized by this family are intricate and neutralization requires interaction with at least two N-linked glycans (N332/N334, N295 or N301) in addition to backbone-mediated contact with the (323)IGDIR(327) motif of the V3 loop. 26837192 6 51 link N-linked 1113:1120 arg1 sites 1136:1140 repositioning critical N-linked glycosylation sites 1090:1140 repositioning critical N-linked glycosylation sites 1090:1140 RESULTS: Using an escape virus isolated from the PGT125-131 donor as a guide, we show that mutating both the V3 core protein epitope and repositioning critical N-linked glycosylation sites are required to restore neutralization sensitivity. 26837192 3 52 theme backbone-mediated 565:581 arg1 contact 583:589 backbone-mediated contact 565:589 backbone-mediated contact with the (323)IGDIR(327) motif of the V3 loop 565:635 The overlapping epitopes recognized by this family are intricate and neutralization requires interaction with at least two N-linked glycans (N332/N334, N295 or N301) in addition to backbone-mediated contact with the (323)IGDIR(327) motif of the V3 loop. 26837192 7 53 theme neutralization 1209:1222 arg1 sensitivity 1224:1234 neutralization sensitivity 1209:1234 neutralization sensitivity 1209:1234 Interestingly, neutralization sensitivity could be restored via different routes for the two distinct bnAb classes within the PGT125-131 family, which may have been important in generating the divergence in recognition. 26837192 1 54 theme neutralizing 109:120 arg1 bnAbs 134:138 bnAbs 134:138 bnAbs 134:138 BACKGROUND: Broadly neutralizing antibodies (bnAbs) directed against the mannose-patch on the HIV envelope glycoprotein gp120 have several features that make them desirable targets for vaccine design. 26837192 1 54 theme neutralizing 109:120 arg1 antibodies 122:131 Broadly neutralizing antibodies 101:131 Broadly neutralizing antibodies (bnAbs) directed against the mannose-patch on the HIV envelope glycoprotein gp120 101:213 BACKGROUND: Broadly neutralizing antibodies (bnAbs) directed against the mannose-patch on the HIV envelope glycoprotein gp120 have several features that make them desirable targets for vaccine design. 26837192 8 55 from resistance 1482:1491 arg1 strains 1508:1514 other virus strains 1496:1514 other virus strains 1496:1514 We demonstrate that the observed V3 mutations confer neutralization resistance in other virus strains through both gain-of-function and escape studies. 26837192 4 56 theme viral 834:838 arg1 escape 840:845 viral escape 834:845 viral escape 834:845 We have recently shown that this bnAb family consists of two distinct antibody classes that can bind alternate arrangements of glycans in the mannose-patch in the absence of N332 thereby limiting viral escape. 26837192 1 57 contain have 215:218 arg1 bnAbs 134:138 bnAbs 134:138 bnAbs 134:138 BACKGROUND: Broadly neutralizing antibodies (bnAbs) directed against the mannose-patch on the HIV envelope glycoprotein gp120 have several features that make them desirable targets for vaccine design. 26837192 1 57 contain have 215:218 arg1 antibodies 122:131 Broadly neutralizing antibodies 101:131 Broadly neutralizing antibodies (bnAbs) directed against the mannose-patch on the HIV envelope glycoprotein gp120 101:213 BACKGROUND: Broadly neutralizing antibodies (bnAbs) directed against the mannose-patch on the HIV envelope glycoprotein gp120 have several features that make them desirable targets for vaccine design. 26837192 1 57 contain have 215:218 arg2 features 228:235 several features 220:235 several features that make them desirable targets for vaccine design 220:287 BACKGROUND: Broadly neutralizing antibodies (bnAbs) directed against the mannose-patch on the HIV envelope glycoprotein gp120 have several features that make them desirable targets for vaccine design. 26837192 6 58 theme V3 1062:1063 arg1 epitope 1078:1084 the V3 core protein epitope 1058:1084 the V3 core protein epitope 1058:1084 RESULTS: Using an escape virus isolated from the PGT125-131 donor as a guide, we show that mutating both the V3 core protein epitope and repositioning critical N-linked glycosylation sites are required to restore neutralization sensitivity. 26837192 10 59 theme V3 1746:1747 arg1 loop 1749:1752 the V3 loop 1742:1752 the V3 loop 1742:1752 CONCLUSIONS: These data highlight the importance of the V3 loop in the design of immunogens aimed at inducing broad and potent bnAbs that can bind promiscuously to the mannose-patch. 26837192 6 60 theme N-linked 1113:1120 arg1 sites 1136:1140 repositioning critical N-linked glycosylation sites 1090:1140 repositioning critical N-linked glycosylation sites 1090:1140 RESULTS: Using an escape virus isolated from the PGT125-131 donor as a guide, we show that mutating both the V3 core protein epitope and repositioning critical N-linked glycosylation sites are required to restore neutralization sensitivity. 26837192 3 61 theme loop 632:635 arg1 motif 616:620 the (323)IGDIR(327) motif 596:620 the (323)IGDIR(327) motif of the V3 loop 596:635 The overlapping epitopes recognized by this family are intricate and neutralization requires interaction with at least two N-linked glycans (N332/N334, N295 or N301) in addition to backbone-mediated contact with the (323)IGDIR(327) motif of the V3 loop. 26837192 5 62 theme PGT125-131 929:938 arg1 family 945:950 the PGT125-131 bnAb family 925:950 the PGT125-131 bnAb family 925:950 This led us to further investigate viral resistance and escape mechanisms to the PGT125-131 bnAb family. 26837192 2 63 theme particular 323:332 arg1 interest 334:341 particular interest 323:341 particular interest 323:341 The PGT125-131 bnAb family is of particular interest due to its superior breadth and potency. 26837192 5 64 theme resistance 889:898 arg1 mechanisms 911:920 viral resistance and escape mechanisms 883:920 viral resistance and escape mechanisms 883:920 This led us to further investigate viral resistance and escape mechanisms to the PGT125-131 bnAb family. 26837192 1 65 theme several 220:226 arg1 features 228:235 several features 220:235 several features that make them desirable targets for vaccine design 220:287 BACKGROUND: Broadly neutralizing antibodies (bnAbs) directed against the mannose-patch on the HIV envelope glycoprotein gp120 have several features that make them desirable targets for vaccine design. 26837192 8 66 theme observed 1438:1445 arg1 mutations 1450:1458 the observed V3 mutations 1434:1458 the observed V3 mutations 1434:1458 We demonstrate that the observed V3 mutations confer neutralization resistance in other virus strains through both gain-of-function and escape studies. 26837192 3 67 theme IGDIR 605:609 arg1 motif 616:620 the (323)IGDIR(327) motif 596:620 the (323)IGDIR(327) motif of the V3 loop 596:635 The overlapping epitopes recognized by this family are intricate and neutralization requires interaction with at least two N-linked glycans (N332/N334, N295 or N301) in addition to backbone-mediated contact with the (323)IGDIR(327) motif of the V3 loop. 26837192 4 68 theme bnAb 671:674 arg1 family 676:681 this bnAb family 666:681 this bnAb family 666:681 We have recently shown that this bnAb family consists of two distinct antibody classes that can bind alternate arrangements of glycans in the mannose-patch in the absence of N332 thereby limiting viral escape. 26837192 7 69 from divergence 1387:1396 arg1 recognition 1401:1411 recognition 1401:1411 recognition 1401:1411 Interestingly, neutralization sensitivity could be restored via different routes for the two distinct bnAb classes within the PGT125-131 family, which may have been important in generating the divergence in recognition. 26837192 3 70 dep requires 468:475 arg1 N301 544:547 N301 544:547 N301 544:547 The overlapping epitopes recognized by this family are intricate and neutralization requires interaction with at least two N-linked glycans (N332/N334, N295 or N301) in addition to backbone-mediated contact with the (323)IGDIR(327) motif of the V3 loop. 26837192 3 70 dep requires 468:475 arg1 N295 536:539 N295 536:539 N295 536:539 The overlapping epitopes recognized by this family are intricate and neutralization requires interaction with at least two N-linked glycans (N332/N334, N295 or N301) in addition to backbone-mediated contact with the (323)IGDIR(327) motif of the V3 loop. 26837192 7 71 theme different 1258:1266 arg1 routes 1268:1273 different routes 1258:1273 different routes for the two distinct bnAb classes within the PGT125-131 family, which may have been important in generating the divergence in recognition 1258:1411 Interestingly, neutralization sensitivity could be restored via different routes for the two distinct bnAb classes within the PGT125-131 family, which may have been important in generating the divergence in recognition. 26837192 7 72 theme distinct 1287:1294 arg1 classes 1301:1307 the two distinct bnAb classes 1279:1307 the two distinct bnAb classes within the PGT125-131 family, which may have been important in generating the divergence in recognition 1279:1411 Interestingly, neutralization sensitivity could be restored via different routes for the two distinct bnAb classes within the PGT125-131 family, which may have been important in generating the divergence in recognition. 26837192 0 73 theme anti-HIV 47:54 arg1 family 37:42 the PGT128 family 26:42 the PGT128 family of anti-HIV 26:54 Mechanisms of escape from the PGT128 family of anti-HIV broadly neutralizing antibodies. 26837192 6 74 attach isolated 984:991 arg1 donor 1013:1017 the PGT125-131 donor 998:1017 the PGT125-131 donor 998:1017 RESULTS: Using an escape virus isolated from the PGT125-131 donor as a guide, we show that mutating both the V3 core protein epitope and repositioning critical N-linked glycosylation sites are required to restore neutralization sensitivity. 26837192 6 74 attach isolated 984:991 arg2 guide 1024:1028 a guide 1022:1028 a guide 1022:1028 RESULTS: Using an escape virus isolated from the PGT125-131 donor as a guide, we show that mutating both the V3 core protein epitope and repositioning critical N-linked glycosylation sites are required to restore neutralization sensitivity. 26837192 6 74 attach isolated 984:991 arg2 virus 978:982 an escape virus 968:982 an escape virus isolated from the PGT125-131 donor 968:1017 RESULTS: Using an escape virus isolated from the PGT125-131 donor as a guide, we show that mutating both the V3 core protein epitope and repositioning critical N-linked glycosylation sites are required to restore neutralization sensitivity. 26837192 4 75 theme alternate 739:747 arg1 arrangements 749:760 alternate arrangements 739:760 alternate arrangements of glycans 739:771 We have recently shown that this bnAb family consists of two distinct antibody classes that can bind alternate arrangements of glycans in the mannose-patch in the absence of N332 thereby limiting viral escape. 26837192 1 76 from mannose-patch 162:174 arg1 gp120 209:213 the HIV envelope glycoprotein gp120 179:213 the HIV envelope glycoprotein gp120 179:213 BACKGROUND: Broadly neutralizing antibodies (bnAbs) directed against the mannose-patch on the HIV envelope glycoprotein gp120 have several features that make them desirable targets for vaccine design. 26837192 2 77 theme superior 354:361 arg1 breadth 363:369 its superior breadth 350:369 its superior breadth 350:369 The PGT125-131 bnAb family is of particular interest due to its superior breadth and potency. 26997012 4 0 theme IgG 587:589 arg1 EIA 611:613 EIA 611:613 EIA 611:613 METHODS: By using commercial mumps IgG enzyme immunoassay (EIA) and a rapid focus reduction neutralization test (FRNT), a panel of serum samples was tested. 26997012 4 0 theme IgG 587:589 arg1 immunoassay 598:608 commercial mumps IgG enzyme immunoassay 570:608 commercial mumps IgG enzyme immunoassay (EIA) 570:614 METHODS: By using commercial mumps IgG enzyme immunoassay (EIA) and a rapid focus reduction neutralization test (FRNT), a panel of serum samples was tested. 26997012 13 1 theme vaccine 1717:1723 arg1 strain 1725:1730 mumps virus vaccine strain 1705:1730 mumps virus vaccine strain 1705:1730 INTERPRETATION & CONCLUSIONS: Good cross-neutralization activity was observed for three mumps virus strains, however, higher level of FRNT titres was detected for mumps virus vaccine strain compared to Indian wild type isolates. 26997012 7 2 theme viruses 1057:1063 arg1 sequence 1033:1040 The HN protein sequence 1018:1040 The HN protein sequence of three mumps viruses 1018:1063 The HN protein sequence of three mumps viruses was analyzed for the presence of key epitopes. 26997012 1 3 theme antibody 263:270 arg1 titres 272:277 mumps virus neutralizing antibody titres 238:277 mumps virus neutralizing antibody titres when tested with vaccine and wild type viruses 238:324 BACKGROUND & OBJECTIVES: The reports from the countries where mumps vaccine is given as routine immunization suggest differences in mumps virus neutralizing antibody titres when tested with vaccine and wild type viruses. 26997012 13 4 theme titres 1681:1686 arg1 level 1667:1671 higher level 1660:1671 higher level of FRNT titres 1660:1686 INTERPRETATION & CONCLUSIONS: Good cross-neutralization activity was observed for three mumps virus strains, however, higher level of FRNT titres was detected for mumps virus vaccine strain compared to Indian wild type isolates. 26997012 8 5 theme virus 1169:1173 arg1 types 1180:1184 mumps virus wild types 1163:1184 mumps virus wild types 1163:1184 RESULTS: All serum samples effectively neutralized mumps virus wild types and a vaccine strain. 26997012 11 6 theme type 1452:1455 arg1 strains 1457:1463 the Indian wild type strains 1436:1463 the Indian wild type strains 1436:1463 No amino acid changes were seen in the epitopes in the Indian wild type strains. 26997012 3 7 theme viruses 543:549 arg1 activity 518:525 the cross-neutralization activity 493:525 the cross-neutralization activity of Indian mumps viruses 493:549 We, therefore, undertook this study to understand the cross-neutralization activity of Indian mumps viruses. 26997012 5 8 theme serum 825:829 arg1 samples 831:837 18 archived serum samples 813:837 18 archived serum samples 813:837 The panel consisted of 14 acute and 14 convalescent serum samples collected during a mumps outbreak and 18 archived serum samples. 26997012 13 9 theme higher 1660:1665 arg1 level 1667:1671 higher level 1660:1671 higher level of FRNT titres 1660:1686 INTERPRETATION & CONCLUSIONS: Good cross-neutralization activity was observed for three mumps virus strains, however, higher level of FRNT titres was detected for mumps virus vaccine strain compared to Indian wild type isolates. 26997012 7 10 theme HN 1022:1023 arg1 sequence 1033:1040 The HN protein sequence 1018:1040 The HN protein sequence of three mumps viruses 1018:1063 The HN protein sequence of three mumps viruses was analyzed for the presence of key epitopes. 26997012 11 11 theme Indian 1440:1445 arg1 strains 1457:1463 the Indian wild type strains 1436:1463 the Indian wild type strains 1436:1463 No amino acid changes were seen in the epitopes in the Indian wild type strains. 26997012 6 12 theme genotype 912:919 arg1 strain 904:909 Leningrad-Zagreb vaccine strain 879:909 Leningrad-Zagreb vaccine strain (genotype N) 879:922 Two wild types (genotypes C and G) and Leningrad-Zagreb vaccine strain (genotype N) were used for the challenge experiments and FRNT titres were determined and further compared. 26997012 6 12 theme genotype 912:919 arg1 N 921:921 genotype N 912:921 genotype N 912:921 Two wild types (genotypes C and G) and Leningrad-Zagreb vaccine strain (genotype N) were used for the challenge experiments and FRNT titres were determined and further compared. 26997012 4 13 theme rapid 622:626 arg1 test 659:662 a rapid focus reduction neutralization test 620:662 a rapid focus reduction neutralization test (FRNT) 620:669 METHODS: By using commercial mumps IgG enzyme immunoassay (EIA) and a rapid focus reduction neutralization test (FRNT), a panel of serum samples was tested. 26997012 4 13 theme rapid 622:626 arg1 FRNT 665:668 FRNT 665:668 FRNT 665:668 METHODS: By using commercial mumps IgG enzyme immunoassay (EIA) and a rapid focus reduction neutralization test (FRNT), a panel of serum samples was tested. 26997012 1 14 theme routine 194:200 arg1 immunization 202:213 routine immunization 194:213 routine immunization 194:213 BACKGROUND & OBJECTIVES: The reports from the countries where mumps vaccine is given as routine immunization suggest differences in mumps virus neutralizing antibody titres when tested with vaccine and wild type viruses. 26997012 1 14 theme routine 194:200 arg1 vaccine 174:180 mumps vaccine 168:180 mumps vaccine 168:180 BACKGROUND & OBJECTIVES: The reports from the countries where mumps vaccine is given as routine immunization suggest differences in mumps virus neutralizing antibody titres when tested with vaccine and wild type viruses. 26997012 4 15 theme reduction 634:642 arg1 test 659:662 a rapid focus reduction neutralization test 620:662 a rapid focus reduction neutralization test (FRNT) 620:669 METHODS: By using commercial mumps IgG enzyme immunoassay (EIA) and a rapid focus reduction neutralization test (FRNT), a panel of serum samples was tested. 26997012 4 15 theme reduction 634:642 arg1 FRNT 665:668 FRNT 665:668 FRNT 665:668 METHODS: By using commercial mumps IgG enzyme immunoassay (EIA) and a rapid focus reduction neutralization test (FRNT), a panel of serum samples was tested. 26997012 4 16 theme mumps 581:585 arg1 EIA 611:613 EIA 611:613 EIA 611:613 METHODS: By using commercial mumps IgG enzyme immunoassay (EIA) and a rapid focus reduction neutralization test (FRNT), a panel of serum samples was tested. 26997012 4 16 theme mumps 581:585 arg1 immunoassay 598:608 commercial mumps IgG enzyme immunoassay 570:608 commercial mumps IgG enzyme immunoassay (EIA) 570:614 METHODS: By using commercial mumps IgG enzyme immunoassay (EIA) and a rapid focus reduction neutralization test (FRNT), a panel of serum samples was tested. 26997012 6 17 theme Leningrad-Zagreb 879:894 arg1 strain 904:909 Leningrad-Zagreb vaccine strain 879:909 Leningrad-Zagreb vaccine strain (genotype N) 879:922 Two wild types (genotypes C and G) and Leningrad-Zagreb vaccine strain (genotype N) were used for the challenge experiments and FRNT titres were determined and further compared. 26997012 6 17 theme Leningrad-Zagreb 879:894 arg1 N 921:921 genotype N 912:921 genotype N 912:921 Two wild types (genotypes C and G) and Leningrad-Zagreb vaccine strain (genotype N) were used for the challenge experiments and FRNT titres were determined and further compared. 26997012 4 18 theme serum 683:687 arg1 samples 689:695 serum samples 683:695 serum samples 683:695 METHODS: By using commercial mumps IgG enzyme immunoassay (EIA) and a rapid focus reduction neutralization test (FRNT), a panel of serum samples was tested. 26997012 12 19 theme potential 1470:1478 arg1 sites 1503:1507 All potential N-linked glycosylation sites 1466:1507 All potential N-linked glycosylation sites 1466:1507 All potential N-linked glycosylation sites were observed in Indian strains. 26997012 11 20 theme acid 1394:1397 arg1 changes 1399:1405 No amino acid changes 1385:1405 No amino acid changes 1385:1405 No amino acid changes were seen in the epitopes in the Indian wild type strains. 26997012 0 21 theme haemagglutinin-neuraminidase 62:89 arg1 epitopes 96:103 haemagglutinin-neuraminidase (HN) epitopes 62:103 haemagglutinin-neuraminidase (HN) epitopes 62:103 Cross-neutralization between three mumps viruses & mapping of haemagglutinin-neuraminidase (HN) epitopes. 26997012 11 22 from epitopes 1424:1431 arg1 strains 1457:1463 the Indian wild type strains 1436:1463 the Indian wild type strains 1436:1463 No amino acid changes were seen in the epitopes in the Indian wild type strains. 26997012 0 23 theme HN 92:93 arg1 epitopes 96:103 haemagglutinin-neuraminidase (HN) epitopes 62:103 haemagglutinin-neuraminidase (HN) epitopes 62:103 Cross-neutralization between three mumps viruses & mapping of haemagglutinin-neuraminidase (HN) epitopes. 26997012 1 24 from countries 152:160 arg1 reports 135:141 The reports 131:141 The reports from the countries where mumps vaccine is given as routine immunization 131:213 BACKGROUND & OBJECTIVES: The reports from the countries where mumps vaccine is given as routine immunization suggest differences in mumps virus neutralizing antibody titres when tested with vaccine and wild type viruses. 26997012 0 25 theme epitopes 96:103 arg1 mapping 51:57 mapping 51:57 mapping of haemagglutinin-neuraminidase (HN) epitopes 51:103 Cross-neutralization between three mumps viruses & mapping of haemagglutinin-neuraminidase (HN) epitopes. 26997012 9 26 theme lower 1231:1235 arg1 titres 1242:1247 significantly lower FRNT titres 1217:1247 significantly lower FRNT titres 1217:1247 However, significantly lower FRNT titres were noted to wild types than to vaccine strain (P<0.05). 26997012 13 27 theme Good 1572:1575 arg1 activity 1598:1605 Good cross-neutralization activity 1572:1605 Good cross-neutralization activity 1572:1605 INTERPRETATION & CONCLUSIONS: Good cross-neutralization activity was observed for three mumps virus strains, however, higher level of FRNT titres was detected for mumps virus vaccine strain compared to Indian wild type isolates. 26997012 1 28 dep OBJECTIVES 119:128 arg1 suggest 215:221 suggest 215:221 suggest differences in mumps virus neutralizing antibody titres when tested with vaccine and wild type viruses 215:324 BACKGROUND & OBJECTIVES: The reports from the countries where mumps vaccine is given as routine immunization suggest differences in mumps virus neutralizing antibody titres when tested with vaccine and wild type viruses. 26997012 13 29 theme type 1756:1759 arg1 isolates 1761:1768 Indian wild type isolates 1744:1768 Indian wild type isolates 1744:1768 INTERPRETATION & CONCLUSIONS: Good cross-neutralization activity was observed for three mumps virus strains, however, higher level of FRNT titres was detected for mumps virus vaccine strain compared to Indian wild type isolates. 26997012 2 30 theme mumps 388:392 arg1 vaccine 394:400 mumps vaccine 388:400 mumps vaccine 388:400 Such reports are unavailable from countries like India where mumps vaccine is not included in routine immunization. 26997012 7 31 theme epitopes 1102:1109 arg1 presence 1086:1093 the presence 1082:1093 the presence of key epitopes 1082:1109 The HN protein sequence of three mumps viruses was analyzed for the presence of key epitopes. 26997012 12 32 theme Indian 1526:1531 arg1 strains 1533:1539 Indian strains 1526:1539 Indian strains 1526:1539 All potential N-linked glycosylation sites were observed in Indian strains. 26997012 13 33 theme INTERPRETATION 1542:1555 arg1 CONCLUSIONS 1559:1569 INTERPRETATION & CONCLUSIONS 1542:1569 INTERPRETATION & CONCLUSIONS: Good cross-neutralization activity was observed for three mumps virus strains, however, higher level of FRNT titres was detected for mumps virus vaccine strain compared to Indian wild type isolates. 1542:1769 INTERPRETATION & CONCLUSIONS: Good cross-neutralization activity was observed for three mumps virus strains, however, higher level of FRNT titres was detected for mumps virus vaccine strain compared to Indian wild type isolates. 26997012 2 34 theme routine 421:427 arg1 immunization 429:440 routine immunization 421:440 routine immunization 421:440 Such reports are unavailable from countries like India where mumps vaccine is not included in routine immunization. 26997012 9 35 theme wild 1263:1266 arg1 types 1268:1272 wild types 1263:1272 wild types than to vaccine strain (P<0.05) 1263:1304 However, significantly lower FRNT titres were noted to wild types than to vaccine strain (P<0.05). 26997012 1 36 theme & 117:117 arg1 OBJECTIVES 119:128 BACKGROUND & OBJECTIVES 106:128 BACKGROUND & OBJECTIVES: The reports from the countries where mumps vaccine is given as routine immunization suggest differences in mumps virus neutralizing antibody titres when tested with vaccine and wild type viruses. 106:325 BACKGROUND & OBJECTIVES: The reports from the countries where mumps vaccine is given as routine immunization suggest differences in mumps virus neutralizing antibody titres when tested with vaccine and wild type viruses. 26997012 13 37 theme Indian 1744:1749 arg1 isolates 1761:1768 Indian wild type isolates 1744:1768 Indian wild type isolates 1744:1768 INTERPRETATION & CONCLUSIONS: Good cross-neutralization activity was observed for three mumps virus strains, however, higher level of FRNT titres was detected for mumps virus vaccine strain compared to Indian wild type isolates. 26997012 5 38 theme archived 816:823 arg1 samples 831:837 18 archived serum samples 813:837 18 archived serum samples 813:837 The panel consisted of 14 acute and 14 convalescent serum samples collected during a mumps outbreak and 18 archived serum samples. 26997012 1 39 theme wild 308:311 arg1 type 313:316 wild type 308:316 wild type 308:316 BACKGROUND & OBJECTIVES: The reports from the countries where mumps vaccine is given as routine immunization suggest differences in mumps virus neutralizing antibody titres when tested with vaccine and wild type viruses. 26997012 6 40 theme FRNT 968:971 arg1 titres 973:978 FRNT titres 968:978 FRNT titres 968:978 Two wild types (genotypes C and G) and Leningrad-Zagreb vaccine strain (genotype N) were used for the challenge experiments and FRNT titres were determined and further compared. 26997012 5 41 theme serum 761:765 arg1 samples 767:773 14 acute and 14 convalescent serum samples 732:773 14 acute and 14 convalescent serum samples collected during a mumps outbreak and 18 archived serum samples 732:837 The panel consisted of 14 acute and 14 convalescent serum samples collected during a mumps outbreak and 18 archived serum samples. 26997012 9 42 theme vaccine 1282:1288 arg1 P<0.05 1298:1303 P<0.05 1298:1303 P<0.05 1298:1303 However, significantly lower FRNT titres were noted to wild types than to vaccine strain (P<0.05). 26997012 9 42 theme vaccine 1282:1288 arg1 strain 1290:1295 vaccine strain 1282:1295 vaccine strain (P<0.05) 1282:1304 However, significantly lower FRNT titres were noted to wild types than to vaccine strain (P<0.05). 26997012 13 43 dep detected 1692:1699 arg1 compared 1732:1739 compared 1732:1739 compared to Indian wild type isolates 1732:1768 INTERPRETATION & CONCLUSIONS: Good cross-neutralization activity was observed for three mumps virus strains, however, higher level of FRNT titres was detected for mumps virus vaccine strain compared to Indian wild type isolates. 26997012 12 44 link N-linked 1480:1487 arg1 sites 1503:1507 All potential N-linked glycosylation sites 1466:1507 All potential N-linked glycosylation sites 1466:1507 All potential N-linked glycosylation sites were observed in Indian strains. 26997012 8 45 theme mumps 1163:1167 arg1 types 1180:1184 mumps virus wild types 1163:1184 mumps virus wild types 1163:1184 RESULTS: All serum samples effectively neutralized mumps virus wild types and a vaccine strain. 26997012 1 46 theme mumps 238:242 arg1 titres 272:277 mumps virus neutralizing antibody titres 238:277 mumps virus neutralizing antibody titres when tested with vaccine and wild type viruses 238:324 BACKGROUND & OBJECTIVES: The reports from the countries where mumps vaccine is given as routine immunization suggest differences in mumps virus neutralizing antibody titres when tested with vaccine and wild type viruses. 26997012 13 47 theme virus 1711:1715 arg1 strain 1725:1730 mumps virus vaccine strain 1705:1730 mumps virus vaccine strain 1705:1730 INTERPRETATION & CONCLUSIONS: Good cross-neutralization activity was observed for three mumps virus strains, however, higher level of FRNT titres was detected for mumps virus vaccine strain compared to Indian wild type isolates. 26997012 7 48 theme mumps 1051:1055 arg1 viruses 1057:1063 three mumps viruses 1045:1063 three mumps viruses 1045:1063 The HN protein sequence of three mumps viruses was analyzed for the presence of key epitopes. 26997012 3 49 theme cross-neutralization 497:516 arg1 activity 518:525 the cross-neutralization activity 493:525 the cross-neutralization activity of Indian mumps viruses 493:549 We, therefore, undertook this study to understand the cross-neutralization activity of Indian mumps viruses. 26997012 1 50 theme neutralizing 250:261 arg1 titres 272:277 mumps virus neutralizing antibody titres 238:277 mumps virus neutralizing antibody titres when tested with vaccine and wild type viruses 238:324 BACKGROUND & OBJECTIVES: The reports from the countries where mumps vaccine is given as routine immunization suggest differences in mumps virus neutralizing antibody titres when tested with vaccine and wild type viruses. 26997012 6 51 dep genotypes 856:864 arg1 C 866:866 C 866:866 C 866:866 Two wild types (genotypes C and G) and Leningrad-Zagreb vaccine strain (genotype N) were used for the challenge experiments and FRNT titres were determined and further compared. 26997012 6 51 dep genotypes 856:864 arg1 genotypes 856:864 genotypes C and G 856:872 genotypes C and G 856:872 Two wild types (genotypes C and G) and Leningrad-Zagreb vaccine strain (genotype N) were used for the challenge experiments and FRNT titres were determined and further compared. 26997012 6 51 dep genotypes 856:864 arg1 G 872:872 G 872:872 G 872:872 Two wild types (genotypes C and G) and Leningrad-Zagreb vaccine strain (genotype N) were used for the challenge experiments and FRNT titres were determined and further compared. 26997012 13 52 theme FRNT 1676:1679 arg1 titres 1681:1686 FRNT titres 1676:1686 FRNT titres 1676:1686 INTERPRETATION & CONCLUSIONS: Good cross-neutralization activity was observed for three mumps virus strains, however, higher level of FRNT titres was detected for mumps virus vaccine strain compared to Indian wild type isolates. 26997012 6 53 used used 929:932 arg2 N 921:921 genotype N 912:921 genotype N 912:921 Two wild types (genotypes C and G) and Leningrad-Zagreb vaccine strain (genotype N) were used for the challenge experiments and FRNT titres were determined and further compared. 26997012 6 53 used used 929:932 arg2 genotypes 856:864 genotypes C and G 856:872 genotypes C and G 856:872 Two wild types (genotypes C and G) and Leningrad-Zagreb vaccine strain (genotype N) were used for the challenge experiments and FRNT titres were determined and further compared. 26997012 6 53 used used 929:932 arg2 strain 904:909 Leningrad-Zagreb vaccine strain 879:909 Leningrad-Zagreb vaccine strain (genotype N) 879:922 Two wild types (genotypes C and G) and Leningrad-Zagreb vaccine strain (genotype N) were used for the challenge experiments and FRNT titres were determined and further compared. 26997012 6 53 used used 929:932 arg2 types 849:853 Two wild types 840:853 Two wild types (genotypes C and G) 840:873 Two wild types (genotypes C and G) and Leningrad-Zagreb vaccine strain (genotype N) were used for the challenge experiments and FRNT titres were determined and further compared. 26997012 12 54 gly glycosylation 1489:1501 arg1 strains 1533:1539 Indian strains 1526:1539 Indian strains 1526:1539 All potential N-linked glycosylation sites were observed in Indian strains. 26997012 12 54 gly glycosylation 1489:1501 arg2 sites 1503:1507 All potential N-linked glycosylation sites 1466:1507 All potential N-linked glycosylation sites 1466:1507 All potential N-linked glycosylation sites were observed in Indian strains. 26997012 4 55 theme enzyme 591:596 arg1 EIA 611:613 EIA 611:613 EIA 611:613 METHODS: By using commercial mumps IgG enzyme immunoassay (EIA) and a rapid focus reduction neutralization test (FRNT), a panel of serum samples was tested. 26997012 4 55 theme enzyme 591:596 arg1 immunoassay 598:608 commercial mumps IgG enzyme immunoassay 570:608 commercial mumps IgG enzyme immunoassay (EIA) 570:614 METHODS: By using commercial mumps IgG enzyme immunoassay (EIA) and a rapid focus reduction neutralization test (FRNT), a panel of serum samples was tested. 26997012 7 56 theme protein 1025:1031 arg1 sequence 1033:1040 The HN protein sequence 1018:1040 The HN protein sequence of three mumps viruses 1018:1063 The HN protein sequence of three mumps viruses was analyzed for the presence of key epitopes. 26997012 3 57 theme mumps 537:541 arg1 viruses 543:549 Indian mumps viruses 530:549 Indian mumps viruses 530:549 We, therefore, undertook this study to understand the cross-neutralization activity of Indian mumps viruses. 26997012 1 58 theme mumps 168:172 arg1 immunization 202:213 routine immunization 194:213 routine immunization 194:213 BACKGROUND & OBJECTIVES: The reports from the countries where mumps vaccine is given as routine immunization suggest differences in mumps virus neutralizing antibody titres when tested with vaccine and wild type viruses. 26997012 1 58 theme mumps 168:172 arg1 vaccine 174:180 mumps vaccine 168:180 mumps vaccine 168:180 BACKGROUND & OBJECTIVES: The reports from the countries where mumps vaccine is given as routine immunization suggest differences in mumps virus neutralizing antibody titres when tested with vaccine and wild type viruses. 26997012 6 59 theme wild 844:847 arg1 types 849:853 Two wild types 840:853 Two wild types (genotypes C and G) 840:873 Two wild types (genotypes C and G) and Leningrad-Zagreb vaccine strain (genotype N) were used for the challenge experiments and FRNT titres were determined and further compared. 26997012 6 59 theme wild 844:847 arg1 genotypes 856:864 genotypes C and G 856:872 genotypes C and G 856:872 Two wild types (genotypes C and G) and Leningrad-Zagreb vaccine strain (genotype N) were used for the challenge experiments and FRNT titres were determined and further compared. 26997012 2 60 from countries 361:369 arg1 unavailable 344:354 unavailable 344:354 unavailable 344:354 Such reports are unavailable from countries like India where mumps vaccine is not included in routine immunization. 26997012 4 61 theme neutralization 644:657 arg1 test 659:662 a rapid focus reduction neutralization test 620:662 a rapid focus reduction neutralization test (FRNT) 620:669 METHODS: By using commercial mumps IgG enzyme immunoassay (EIA) and a rapid focus reduction neutralization test (FRNT), a panel of serum samples was tested. 26997012 4 61 theme neutralization 644:657 arg1 FRNT 665:668 FRNT 665:668 FRNT 665:668 METHODS: By using commercial mumps IgG enzyme immunoassay (EIA) and a rapid focus reduction neutralization test (FRNT), a panel of serum samples was tested. 26997012 5 62 theme acute 735:739 arg1 samples 767:773 14 acute and 14 convalescent serum samples 732:773 14 acute and 14 convalescent serum samples collected during a mumps outbreak and 18 archived serum samples 732:837 The panel consisted of 14 acute and 14 convalescent serum samples collected during a mumps outbreak and 18 archived serum samples. 26997012 8 63 theme wild 1175:1178 arg1 types 1180:1184 mumps virus wild types 1163:1184 mumps virus wild types 1163:1184 RESULTS: All serum samples effectively neutralized mumps virus wild types and a vaccine strain. 26997012 11 64 theme wild 1447:1450 arg1 strains 1457:1463 the Indian wild type strains 1436:1463 the Indian wild type strains 1436:1463 No amino acid changes were seen in the epitopes in the Indian wild type strains. 26997012 5 65 theme mumps 794:798 arg1 outbreak 800:807 a mumps outbreak 792:807 a mumps outbreak 792:807 The panel consisted of 14 acute and 14 convalescent serum samples collected during a mumps outbreak and 18 archived serum samples. 26997012 13 66 theme virus 1636:1640 arg1 strains 1642:1648 three mumps virus strains 1624:1648 three mumps virus strains 1624:1648 INTERPRETATION & CONCLUSIONS: Good cross-neutralization activity was observed for three mumps virus strains, however, higher level of FRNT titres was detected for mumps virus vaccine strain compared to Indian wild type isolates. 26997012 8 67 theme serum 1125:1129 arg1 samples 1131:1137 All serum samples 1121:1137 All serum samples 1121:1137 RESULTS: All serum samples effectively neutralized mumps virus wild types and a vaccine strain. 26997012 6 68 theme vaccine 896:902 arg1 strain 904:909 Leningrad-Zagreb vaccine strain 879:909 Leningrad-Zagreb vaccine strain (genotype N) 879:922 Two wild types (genotypes C and G) and Leningrad-Zagreb vaccine strain (genotype N) were used for the challenge experiments and FRNT titres were determined and further compared. 26997012 6 68 theme vaccine 896:902 arg1 N 921:921 genotype N 912:921 genotype N 912:921 Two wild types (genotypes C and G) and Leningrad-Zagreb vaccine strain (genotype N) were used for the challenge experiments and FRNT titres were determined and further compared. 26997012 4 69 theme focus 628:632 arg1 test 659:662 a rapid focus reduction neutralization test 620:662 a rapid focus reduction neutralization test (FRNT) 620:669 METHODS: By using commercial mumps IgG enzyme immunoassay (EIA) and a rapid focus reduction neutralization test (FRNT), a panel of serum samples was tested. 26997012 4 69 theme focus 628:632 arg1 FRNT 665:668 FRNT 665:668 FRNT 665:668 METHODS: By using commercial mumps IgG enzyme immunoassay (EIA) and a rapid focus reduction neutralization test (FRNT), a panel of serum samples was tested. 26997012 12 70 theme glycosylation 1489:1501 arg1 sites 1503:1507 All potential N-linked glycosylation sites 1466:1507 All potential N-linked glycosylation sites 1466:1507 All potential N-linked glycosylation sites were observed in Indian strains. 26997012 12 71 theme N-linked 1480:1487 arg1 sites 1503:1507 All potential N-linked glycosylation sites 1466:1507 All potential N-linked glycosylation sites 1466:1507 All potential N-linked glycosylation sites were observed in Indian strains. 26997012 11 72 theme amino 1388:1392 arg1 changes 1399:1405 No amino acid changes 1385:1405 No amino acid changes 1385:1405 No amino acid changes were seen in the epitopes in the Indian wild type strains. 26997012 1 73 from differences 223:233 arg1 titres 272:277 mumps virus neutralizing antibody titres 238:277 mumps virus neutralizing antibody titres when tested with vaccine and wild type viruses 238:324 BACKGROUND & OBJECTIVES: The reports from the countries where mumps vaccine is given as routine immunization suggest differences in mumps virus neutralizing antibody titres when tested with vaccine and wild type viruses. 26997012 12 74 located observed 1514:1521 arg1 strains 1533:1539 Indian strains 1526:1539 Indian strains 1526:1539 All potential N-linked glycosylation sites were observed in Indian strains. 26997012 12 74 located observed 1514:1521 arg2 sites 1503:1507 All potential N-linked glycosylation sites 1466:1507 All potential N-linked glycosylation sites 1466:1507 All potential N-linked glycosylation sites were observed in Indian strains. 26997012 4 75 theme samples 689:695 arg1 panel 674:678 a panel 672:678 a panel of serum samples 672:695 METHODS: By using commercial mumps IgG enzyme immunoassay (EIA) and a rapid focus reduction neutralization test (FRNT), a panel of serum samples was tested. 26997012 6 76 theme challenge 942:950 arg1 experiments 952:962 the challenge experiments 938:962 the challenge experiments 938:962 Two wild types (genotypes C and G) and Leningrad-Zagreb vaccine strain (genotype N) were used for the challenge experiments and FRNT titres were determined and further compared. 26997012 1 77 dep vaccine 296:302 arg1 viruses 318:324 viruses 318:324 viruses 318:324 BACKGROUND & OBJECTIVES: The reports from the countries where mumps vaccine is given as routine immunization suggest differences in mumps virus neutralizing antibody titres when tested with vaccine and wild type viruses. 26997012 13 78 theme mumps 1630:1634 arg1 strains 1642:1648 three mumps virus strains 1624:1648 three mumps virus strains 1624:1648 INTERPRETATION & CONCLUSIONS: Good cross-neutralization activity was observed for three mumps virus strains, however, higher level of FRNT titres was detected for mumps virus vaccine strain compared to Indian wild type isolates. 26997012 13 79 theme wild 1751:1754 arg1 isolates 1761:1768 Indian wild type isolates 1744:1768 Indian wild type isolates 1744:1768 INTERPRETATION & CONCLUSIONS: Good cross-neutralization activity was observed for three mumps virus strains, however, higher level of FRNT titres was detected for mumps virus vaccine strain compared to Indian wild type isolates. 26997012 9 80 theme FRNT 1237:1240 arg1 titres 1242:1247 significantly lower FRNT titres 1217:1247 significantly lower FRNT titres 1217:1247 However, significantly lower FRNT titres were noted to wild types than to vaccine strain (P<0.05). 26997012 13 81 theme cross-neutralization 1577:1596 arg1 activity 1598:1605 Good cross-neutralization activity 1572:1605 Good cross-neutralization activity 1572:1605 INTERPRETATION & CONCLUSIONS: Good cross-neutralization activity was observed for three mumps virus strains, however, higher level of FRNT titres was detected for mumps virus vaccine strain compared to Indian wild type isolates. 26997012 7 82 theme key 1098:1100 arg1 epitopes 1102:1109 key epitopes 1098:1109 key epitopes 1098:1109 The HN protein sequence of three mumps viruses was analyzed for the presence of key epitopes. 26997012 10 83 theme 95.6 1360:1363 arg1 agreement 1374:1382 95.6 per cent agreement 1360:1382 95.6 per cent agreement 1360:1382 The comparison between EIA and FRNT results revealed 95.6 per cent agreement. 26997012 0 84 theme mumps 35:39 arg1 viruses 41:47 three mumps viruses 29:47 three mumps viruses 29:47 Cross-neutralization between three mumps viruses & mapping of haemagglutinin-neuraminidase (HN) epitopes. 26997012 1 85 theme BACKGROUND 106:115 arg1 OBJECTIVES 119:128 BACKGROUND & OBJECTIVES 106:128 BACKGROUND & OBJECTIVES: The reports from the countries where mumps vaccine is given as routine immunization suggest differences in mumps virus neutralizing antibody titres when tested with vaccine and wild type viruses. 106:325 BACKGROUND & OBJECTIVES: The reports from the countries where mumps vaccine is given as routine immunization suggest differences in mumps virus neutralizing antibody titres when tested with vaccine and wild type viruses. 26997012 4 86 theme commercial 570:579 arg1 EIA 611:613 EIA 611:613 EIA 611:613 METHODS: By using commercial mumps IgG enzyme immunoassay (EIA) and a rapid focus reduction neutralization test (FRNT), a panel of serum samples was tested. 26997012 4 86 theme commercial 570:579 arg1 immunoassay 598:608 commercial mumps IgG enzyme immunoassay 570:608 commercial mumps IgG enzyme immunoassay (EIA) 570:614 METHODS: By using commercial mumps IgG enzyme immunoassay (EIA) and a rapid focus reduction neutralization test (FRNT), a panel of serum samples was tested. 26997012 13 87 theme & 1557:1557 arg1 CONCLUSIONS 1559:1569 INTERPRETATION & CONCLUSIONS 1542:1569 INTERPRETATION & CONCLUSIONS: Good cross-neutralization activity was observed for three mumps virus strains, however, higher level of FRNT titres was detected for mumps virus vaccine strain compared to Indian wild type isolates. 1542:1769 INTERPRETATION & CONCLUSIONS: Good cross-neutralization activity was observed for three mumps virus strains, however, higher level of FRNT titres was detected for mumps virus vaccine strain compared to Indian wild type isolates. 26997012 5 88 theme convalescent 748:759 arg1 samples 767:773 14 acute and 14 convalescent serum samples 732:773 14 acute and 14 convalescent serum samples collected during a mumps outbreak and 18 archived serum samples 732:837 The panel consisted of 14 acute and 14 convalescent serum samples collected during a mumps outbreak and 18 archived serum samples. 26997012 2 89 theme Such 327:330 arg1 reports 332:338 Such reports 327:338 Such reports 327:338 Such reports are unavailable from countries like India where mumps vaccine is not included in routine immunization. 26997012 10 90 dep EIA 1330:1332 arg1 results 1343:1349 results 1343:1349 results 1343:1349 The comparison between EIA and FRNT results revealed 95.6 per cent agreement. 26997012 13 91 dep CONCLUSIONS 1559:1569 arg1 observed 1611:1618 observed 1611:1618 was observed for three mumps virus strains 1607:1648 INTERPRETATION & CONCLUSIONS: Good cross-neutralization activity was observed for three mumps virus strains, however, higher level of FRNT titres was detected for mumps virus vaccine strain compared to Indian wild type isolates. 26997012 8 92 theme vaccine 1192:1198 arg1 strain 1200:1205 a vaccine strain 1190:1205 a vaccine strain 1190:1205 RESULTS: All serum samples effectively neutralized mumps virus wild types and a vaccine strain. 26997012 13 93 theme mumps 1705:1709 arg1 strain 1725:1730 mumps virus vaccine strain 1705:1730 mumps virus vaccine strain 1705:1730 INTERPRETATION & CONCLUSIONS: Good cross-neutralization activity was observed for three mumps virus strains, however, higher level of FRNT titres was detected for mumps virus vaccine strain compared to Indian wild type isolates. 26997012 3 94 theme Indian 530:535 arg1 viruses 543:549 Indian mumps viruses 530:549 Indian mumps viruses 530:549 We, therefore, undertook this study to understand the cross-neutralization activity of Indian mumps viruses. 26997012 1 95 theme virus 244:248 arg1 titres 272:277 mumps virus neutralizing antibody titres 238:277 mumps virus neutralizing antibody titres when tested with vaccine and wild type viruses 238:324 BACKGROUND & OBJECTIVES: The reports from the countries where mumps vaccine is given as routine immunization suggest differences in mumps virus neutralizing antibody titres when tested with vaccine and wild type viruses. 25651845 3 0 theme clotting 600:607 arg1 % 597:597 36% 595:597 36% (clotting assay) 595:614 A recent cohort study aimed at establishing a normal PC range identified a healthy PC-deficient subject whose PC antigen level of 65% and activity levels of 50% (chromogenic assay) and 36% (clotting assay) were markedly low. 25651845 3 0 theme clotting 600:607 arg1 assay 609:613 clotting assay 600:613 clotting assay 600:613 A recent cohort study aimed at establishing a normal PC range identified a healthy PC-deficient subject whose PC antigen level of 65% and activity levels of 50% (chromogenic assay) and 36% (clotting assay) were markedly low. 25651845 7 1 theme mutant 1005:1010 arg1 activities 967:976 both anticoagulant and anti-inflammatory activities 926:976 both anticoagulant and anti-inflammatory activities of the activated protein C mutant 926:1010 A similar decrease in both anticoagulant and anti-inflammatory activities of the activated protein C mutant was observed in plasma- and cell-based assays. 25651845 7 2 theme similar 906:912 arg1 decrease 914:921 A similar decrease 904:921 A similar decrease in both anticoagulant and anti-inflammatory activities of the activated protein C mutant 904:1010 A similar decrease in both anticoagulant and anti-inflammatory activities of the activated protein C mutant was observed in plasma- and cell-based assays. 25651845 7 3 theme anti-inflammatory 949:965 arg1 activities 967:976 both anticoagulant and anti-inflammatory activities 926:976 both anticoagulant and anti-inflammatory activities of the activated protein C mutant 926:1010 A similar decrease in both anticoagulant and anti-inflammatory activities of the activated protein C mutant was observed in plasma- and cell-based assays. 25651845 1 4 theme feedback 290:297 arg1 mechanism 315:323 a feedback loop inhibition mechanism 288:323 a feedback loop inhibition mechanism 288:323 Protein C (PC) is a vitamin K-dependent plasma glycoprotein, which upon activation by thrombin in complex with thrombomodulin (TM), regulates the coagulation cascade through a feedback loop inhibition mechanism. 25651845 5 5 theme PC 784:785 arg1 chain 793:797 the PC heavy chain 780:797 the PC heavy chain 780:797 Genetic analysis revealed the proband has a heterozygous missense mutation in which Thr-315 of the PC heavy chain has been substituted with Ala. 25651845 1 6 theme loop 299:302 arg1 mechanism 315:323 a feedback loop inhibition mechanism 288:323 a feedback loop inhibition mechanism 288:323 Protein C (PC) is a vitamin K-dependent plasma glycoprotein, which upon activation by thrombin in complex with thrombomodulin (TM), regulates the coagulation cascade through a feedback loop inhibition mechanism. 25651845 7 7 theme protein 995:1001 arg1 C 1003:1003 the activated protein C 981:1003 the activated protein C mutant 981:1010 A similar decrease in both anticoagulant and anti-inflammatory activities of the activated protein C mutant was observed in plasma- and cell-based assays. 25651845 3 8 theme normal 456:461 arg1 range 466:470 a normal PC range 454:470 a normal PC range 454:470 A recent cohort study aimed at establishing a normal PC range identified a healthy PC-deficient subject whose PC antigen level of 65% and activity levels of 50% (chromogenic assay) and 36% (clotting assay) were markedly low. 25651845 9 9 theme thrombin-TM 1427:1437 arg1 complex 1439:1445 the thrombin-TM complex 1423:1445 the thrombin-TM complex 1423:1445 Sequence analysis revealed Thr-315 is a consensus N-linked glycosylation site for Asn-313 and that its elimination significantly (∼four- to fivefold) improves the maximum velocity of PC activation by the thrombin-TM complex, explaining the basis for the proband's negative VTE pedigree. 25651845 0 10 theme type 73:76 arg1 deficiency 81:90 type II deficiency 73:90 type II deficiency in diagnostic assays 73:111 Protein C Thr315Ala variant results in gain of function but manifests as type II deficiency in diagnostic assays. 25651845 1 11 theme inhibition 304:313 arg1 mechanism 315:323 a feedback loop inhibition mechanism 288:323 a feedback loop inhibition mechanism 288:323 Protein C (PC) is a vitamin K-dependent plasma glycoprotein, which upon activation by thrombin in complex with thrombomodulin (TM), regulates the coagulation cascade through a feedback loop inhibition mechanism. 25651845 7 12 theme C 1003:1003 arg1 mutant 1005:1010 the activated protein C mutant 981:1010 the activated protein C mutant 981:1010 A similar decrease in both anticoagulant and anti-inflammatory activities of the activated protein C mutant was observed in plasma- and cell-based assays. 25651845 3 13 theme healthy 485:491 arg1 subject 506:512 a healthy PC-deficient subject 483:512 a healthy PC-deficient subject whose PC antigen level of 65% and activity levels of 50% (chromogenic assay) and 36% (clotting assay) were markedly low 483:632 A recent cohort study aimed at establishing a normal PC range identified a healthy PC-deficient subject whose PC antigen level of 65% and activity levels of 50% (chromogenic assay) and 36% (clotting assay) were markedly low. 25651845 6 14 theme HEK-293 858:864 arg1 cells 866:870 HEK-293 cells 858:870 HEK-293 cells 858:870 We expressed this mutant in HEK-293 cells and purified it to homogeneity. 25651845 9 15 theme activation 1409:1418 arg1 velocity 1394:1401 the maximum velocity 1382:1401 the maximum velocity of PC activation by the thrombin-TM complex 1382:1445 Sequence analysis revealed Thr-315 is a consensus N-linked glycosylation site for Asn-313 and that its elimination significantly (∼four- to fivefold) improves the maximum velocity of PC activation by the thrombin-TM complex, explaining the basis for the proband's negative VTE pedigree. 25651845 1 16 gly glycoprotein 161:172 arg1 glycoprotein 161:172 a vitamin K-dependent plasma glycoprotein 132:172 a vitamin K-dependent plasma glycoprotein 132:172 Protein C (PC) is a vitamin K-dependent plasma glycoprotein, which upon activation by thrombin in complex with thrombomodulin (TM), regulates the coagulation cascade through a feedback loop inhibition mechanism. 25651845 1 16 gly glycoprotein 161:172 arg1 C 122:122 Protein C 114:122 Protein C (PC) 114:127 Protein C (PC) is a vitamin K-dependent plasma glycoprotein, which upon activation by thrombin in complex with thrombomodulin (TM), regulates the coagulation cascade through a feedback loop inhibition mechanism. 25651845 5 17 theme Genetic 685:691 arg1 analysis 693:700 Genetic analysis 685:700 Genetic analysis 685:700 Genetic analysis revealed the proband has a heterozygous missense mutation in which Thr-315 of the PC heavy chain has been substituted with Ala. 25651845 4 18 theme family 662:667 arg1 history 669:675 a negative family history 651:675 a negative family history of VTE 651:682 The proband has a negative family history of VTE. 25651845 5 19 theme missense 742:749 arg1 mutation 751:758 a heterozygous missense mutation 727:758 a heterozygous missense mutation in which Thr-315 of the PC heavy chain has been substituted with Ala. 727:828 Genetic analysis revealed the proband has a heterozygous missense mutation in which Thr-315 of the PC heavy chain has been substituted with Ala. 25651845 7 20 theme activated 985:993 arg1 C 1003:1003 the activated protein C 981:1003 the activated protein C mutant 981:1010 A similar decrease in both anticoagulant and anti-inflammatory activities of the activated protein C mutant was observed in plasma- and cell-based assays. 25651845 9 21 theme PC 1406:1407 arg1 activation 1409:1418 PC activation 1406:1418 PC activation 1406:1418 Sequence analysis revealed Thr-315 is a consensus N-linked glycosylation site for Asn-313 and that its elimination significantly (∼four- to fivefold) improves the maximum velocity of PC activation by the thrombin-TM complex, explaining the basis for the proband's negative VTE pedigree. 25651845 4 22 theme negative 653:660 arg1 history 669:675 a negative family history 651:675 a negative family history of VTE 651:682 The proband has a negative family history of VTE. 25651845 4 23 contain has 647:649 arg2 history 669:675 a negative family history 651:675 a negative family history of VTE 651:682 The proband has a negative family history of VTE. 25651845 4 23 contain has 647:649 arg1 proband 639:645 The proband 635:645 The proband 635:645 The proband has a negative family history of VTE. 25651845 0 24 theme C 8:8 arg1 variant 20:26 Protein C Thr315Ala variant 0:26 Protein C Thr315Ala variant 0:26 Protein C Thr315Ala variant results in gain of function but manifests as type II deficiency in diagnostic assays. 25651845 1 25 theme vitamin 134:140 arg1 glycoprotein 161:172 a vitamin K-dependent plasma glycoprotein 132:172 a vitamin K-dependent plasma glycoprotein 132:172 Protein C (PC) is a vitamin K-dependent plasma glycoprotein, which upon activation by thrombin in complex with thrombomodulin (TM), regulates the coagulation cascade through a feedback loop inhibition mechanism. 25651845 1 25 theme vitamin 134:140 arg1 C 122:122 Protein C 114:122 Protein C (PC) 114:127 Protein C (PC) is a vitamin K-dependent plasma glycoprotein, which upon activation by thrombin in complex with thrombomodulin (TM), regulates the coagulation cascade through a feedback loop inhibition mechanism. 25651845 0 26 theme Protein 0:6 arg1 variant 20:26 Protein C Thr315Ala variant 0:26 Protein C Thr315Ala variant 0:26 Protein C Thr315Ala variant results in gain of function but manifests as type II deficiency in diagnostic assays. 25651845 5 27 contain has 723:725 arg1 analysis 693:700 Genetic analysis 685:700 Genetic analysis 685:700 Genetic analysis revealed the proband has a heterozygous missense mutation in which Thr-315 of the PC heavy chain has been substituted with Ala. 25651845 5 27 contain has 723:725 arg2 mutation 751:758 a heterozygous missense mutation 727:758 a heterozygous missense mutation in which Thr-315 of the PC heavy chain has been substituted with Ala. 727:828 Genetic analysis revealed the proband has a heterozygous missense mutation in which Thr-315 of the PC heavy chain has been substituted with Ala. 25651845 5 27 contain has 723:725 arg1 proband 715:721 the proband 711:721 the proband 711:721 Genetic analysis revealed the proband has a heterozygous missense mutation in which Thr-315 of the PC heavy chain has been substituted with Ala. 25651845 3 28 theme PC 520:521 arg1 level 531:535 PC antigen level 520:535 PC antigen level of 65% 520:542 A recent cohort study aimed at establishing a normal PC range identified a healthy PC-deficient subject whose PC antigen level of 65% and activity levels of 50% (chromogenic assay) and 36% (clotting assay) were markedly low. 25651845 1 29 theme K-dependent 142:152 arg1 glycoprotein 161:172 a vitamin K-dependent plasma glycoprotein 132:172 a vitamin K-dependent plasma glycoprotein 132:172 Protein C (PC) is a vitamin K-dependent plasma glycoprotein, which upon activation by thrombin in complex with thrombomodulin (TM), regulates the coagulation cascade through a feedback loop inhibition mechanism. 25651845 1 29 theme K-dependent 142:152 arg1 C 122:122 Protein C 114:122 Protein C (PC) 114:127 Protein C (PC) is a vitamin K-dependent plasma glycoprotein, which upon activation by thrombin in complex with thrombomodulin (TM), regulates the coagulation cascade through a feedback loop inhibition mechanism. 25651845 2 30 theme thromboembolism 387:401 arg1 risk 372:375 an increased risk 359:375 an increased risk of venous thromboembolism (VTE) 359:407 PC deficiency is associated with an increased risk of venous thromboembolism (VTE). 25651845 9 31 link N-linked 1273:1280 arg1 site 1296:1299 a consensus N-linked glycosylation site 1261:1299 a consensus N-linked glycosylation site for Asn-313 1261:1311 Sequence analysis revealed Thr-315 is a consensus N-linked glycosylation site for Asn-313 and that its elimination significantly (∼four- to fivefold) improves the maximum velocity of PC activation by the thrombin-TM complex, explaining the basis for the proband's negative VTE pedigree. 25651845 9 31 link N-linked 1273:1280 arg1 Thr-315 1250:1256 Thr-315 1250:1256 Thr-315 1250:1256 Sequence analysis revealed Thr-315 is a consensus N-linked glycosylation site for Asn-313 and that its elimination significantly (∼four- to fivefold) improves the maximum velocity of PC activation by the thrombin-TM complex, explaining the basis for the proband's negative VTE pedigree. 25651845 9 32 dep fivefold 1363:1370 arg1 to 1360:1361 to 1360:1361 to 1360:1361 Sequence analysis revealed Thr-315 is a consensus N-linked glycosylation site for Asn-313 and that its elimination significantly (∼four- to fivefold) improves the maximum velocity of PC activation by the thrombin-TM complex, explaining the basis for the proband's negative VTE pedigree. 25651845 7 33 located observed 1016:1023 arg1 plasma- 1028:1034 plasma- 1028:1034 plasma- 1028:1034 A similar decrease in both anticoagulant and anti-inflammatory activities of the activated protein C mutant was observed in plasma- and cell-based assays. 25651845 7 33 located observed 1016:1023 arg1 assays 1051:1056 cell-based assays 1040:1056 cell-based assays 1040:1056 A similar decrease in both anticoagulant and anti-inflammatory activities of the activated protein C mutant was observed in plasma- and cell-based assays. 25651845 7 33 located observed 1016:1023 arg2 decrease 914:921 A similar decrease 904:921 A similar decrease in both anticoagulant and anti-inflammatory activities of the activated protein C mutant 904:1010 A similar decrease in both anticoagulant and anti-inflammatory activities of the activated protein C mutant was observed in plasma- and cell-based assays. 25651845 3 34 theme PC-deficient 493:504 arg1 subject 506:512 a healthy PC-deficient subject 483:512 a healthy PC-deficient subject whose PC antigen level of 65% and activity levels of 50% (chromogenic assay) and 36% (clotting assay) were markedly low 483:632 A recent cohort study aimed at establishing a normal PC range identified a healthy PC-deficient subject whose PC antigen level of 65% and activity levels of 50% (chromogenic assay) and 36% (clotting assay) were markedly low. 25651845 9 35 theme consensus 1263:1271 arg1 site 1296:1299 a consensus N-linked glycosylation site 1261:1299 a consensus N-linked glycosylation site for Asn-313 1261:1311 Sequence analysis revealed Thr-315 is a consensus N-linked glycosylation site for Asn-313 and that its elimination significantly (∼four- to fivefold) improves the maximum velocity of PC activation by the thrombin-TM complex, explaining the basis for the proband's negative VTE pedigree. 25651845 9 35 theme consensus 1263:1271 arg1 Thr-315 1250:1256 Thr-315 1250:1256 Thr-315 1250:1256 Sequence analysis revealed Thr-315 is a consensus N-linked glycosylation site for Asn-313 and that its elimination significantly (∼four- to fivefold) improves the maximum velocity of PC activation by the thrombin-TM complex, explaining the basis for the proband's negative VTE pedigree. 25651845 1 36 theme plasma 154:159 arg1 glycoprotein 161:172 a vitamin K-dependent plasma glycoprotein 132:172 a vitamin K-dependent plasma glycoprotein 132:172 Protein C (PC) is a vitamin K-dependent plasma glycoprotein, which upon activation by thrombin in complex with thrombomodulin (TM), regulates the coagulation cascade through a feedback loop inhibition mechanism. 25651845 1 36 theme plasma 154:159 arg1 C 122:122 Protein C 114:122 Protein C (PC) 114:127 Protein C (PC) is a vitamin K-dependent plasma glycoprotein, which upon activation by thrombin in complex with thrombomodulin (TM), regulates the coagulation cascade through a feedback loop inhibition mechanism. 25651845 2 37 theme venous 380:385 arg1 VTE 404:406 VTE 404:406 VTE 404:406 PC deficiency is associated with an increased risk of venous thromboembolism (VTE). 25651845 2 37 theme venous 380:385 arg1 thromboembolism 387:401 venous thromboembolism 380:401 venous thromboembolism (VTE) 380:407 PC deficiency is associated with an increased risk of venous thromboembolism (VTE). 25651845 0 38 theme diagnostic 95:104 arg1 assays 106:111 diagnostic assays 95:111 diagnostic assays 95:111 Protein C Thr315Ala variant results in gain of function but manifests as type II deficiency in diagnostic assays. 25651845 3 39 theme % 569:569 arg1 level 531:535 PC antigen level 520:535 PC antigen level of 65% 520:542 A recent cohort study aimed at establishing a normal PC range identified a healthy PC-deficient subject whose PC antigen level of 65% and activity levels of 50% (chromogenic assay) and 36% (clotting assay) were markedly low. 25651845 3 39 theme % 569:569 arg1 levels 557:562 activity levels 548:562 activity levels of 50% (chromogenic assay) and 36% (clotting assay) 548:614 A recent cohort study aimed at establishing a normal PC range identified a healthy PC-deficient subject whose PC antigen level of 65% and activity levels of 50% (chromogenic assay) and 36% (clotting assay) were markedly low. 25651845 3 40 theme recent 412:417 arg1 study 426:430 A recent cohort study 410:430 A recent cohort study aimed at establishing a normal PC range 410:470 A recent cohort study aimed at establishing a normal PC range identified a healthy PC-deficient subject whose PC antigen level of 65% and activity levels of 50% (chromogenic assay) and 36% (clotting assay) were markedly low. 25651845 9 41 theme maximum 1386:1392 arg1 velocity 1394:1401 the maximum velocity 1382:1401 the maximum velocity of PC activation by the thrombin-TM complex 1382:1445 Sequence analysis revealed Thr-315 is a consensus N-linked glycosylation site for Asn-313 and that its elimination significantly (∼four- to fivefold) improves the maximum velocity of PC activation by the thrombin-TM complex, explaining the basis for the proband's negative VTE pedigree. 25651845 9 42 dep revealed 1241:1248 arg1 site 1296:1299 a consensus N-linked glycosylation site 1261:1299 a consensus N-linked glycosylation site for Asn-313 1261:1311 Sequence analysis revealed Thr-315 is a consensus N-linked glycosylation site for Asn-313 and that its elimination significantly (∼four- to fivefold) improves the maximum velocity of PC activation by the thrombin-TM complex, explaining the basis for the proband's negative VTE pedigree. 25651845 9 42 dep revealed 1241:1248 arg1 Thr-315 1250:1256 Thr-315 1250:1256 Thr-315 1250:1256 Sequence analysis revealed Thr-315 is a consensus N-linked glycosylation site for Asn-313 and that its elimination significantly (∼four- to fivefold) improves the maximum velocity of PC activation by the thrombin-TM complex, explaining the basis for the proband's negative VTE pedigree. 25651845 9 42 dep revealed 1241:1248 arg1 improves 1373:1380 improves 1373:1380 improves 1373:1380 Sequence analysis revealed Thr-315 is a consensus N-linked glycosylation site for Asn-313 and that its elimination significantly (∼four- to fivefold) improves the maximum velocity of PC activation by the thrombin-TM complex, explaining the basis for the proband's negative VTE pedigree. 25651845 9 43 gly glycosylation 1282:1294 arg2 Thr-315 1250:1256 Thr-315 1250:1256 Thr-315 1250:1256 Sequence analysis revealed Thr-315 is a consensus N-linked glycosylation site for Asn-313 and that its elimination significantly (∼four- to fivefold) improves the maximum velocity of PC activation by the thrombin-TM complex, explaining the basis for the proband's negative VTE pedigree. 25651845 9 43 gly glycosylation 1282:1294 arg2 site 1296:1299 a consensus N-linked glycosylation site 1261:1299 a consensus N-linked glycosylation site for Asn-313 1261:1311 Sequence analysis revealed Thr-315 is a consensus N-linked glycosylation site for Asn-313 and that its elimination significantly (∼four- to fivefold) improves the maximum velocity of PC activation by the thrombin-TM complex, explaining the basis for the proband's negative VTE pedigree. 25651845 2 44 theme increased 362:370 arg1 risk 372:375 an increased risk 359:375 an increased risk of venous thromboembolism (VTE) 359:407 PC deficiency is associated with an increased risk of venous thromboembolism (VTE). 25651845 8 45 theme PC 1125:1126 arg1 activation 1128:1137 PC activation 1125:1137 PC activation by the thrombin-TM complex 1125:1164 Interestingly, we discovered if functional assays were coupled to PC activation by the thrombin-TM complex, the variant exhibits improved activities in all assays. 25651845 7 46 theme anticoagulant 931:943 arg1 activities 967:976 both anticoagulant and anti-inflammatory activities 926:976 both anticoagulant and anti-inflammatory activities of the activated protein C mutant 926:1010 A similar decrease in both anticoagulant and anti-inflammatory activities of the activated protein C mutant was observed in plasma- and cell-based assays. 25651845 9 47 dep significantly 1338:1350 arg1 fivefold 1363:1370 fivefold 1363:1370 fivefold 1363:1370 Sequence analysis revealed Thr-315 is a consensus N-linked glycosylation site for Asn-313 and that its elimination significantly (∼four- to fivefold) improves the maximum velocity of PC activation by the thrombin-TM complex, explaining the basis for the proband's negative VTE pedigree. 25651845 7 48 theme cell-based 1040:1049 arg1 assays 1051:1056 cell-based assays 1040:1056 cell-based assays 1040:1056 A similar decrease in both anticoagulant and anti-inflammatory activities of the activated protein C mutant was observed in plasma- and cell-based assays. 25651845 5 49 theme heterozygous 729:740 arg1 mutation 751:758 a heterozygous missense mutation 727:758 a heterozygous missense mutation in which Thr-315 of the PC heavy chain has been substituted with Ala. 727:828 Genetic analysis revealed the proband has a heterozygous missense mutation in which Thr-315 of the PC heavy chain has been substituted with Ala. 25651845 8 50 theme functional 1091:1100 arg1 assays 1102:1107 functional assays 1091:1107 functional assays 1091:1107 Interestingly, we discovered if functional assays were coupled to PC activation by the thrombin-TM complex, the variant exhibits improved activities in all assays. 25651845 9 51 theme Sequence 1223:1230 arg1 analysis 1232:1239 Sequence analysis 1223:1239 Sequence analysis 1223:1239 Sequence analysis revealed Thr-315 is a consensus N-linked glycosylation site for Asn-313 and that its elimination significantly (∼four- to fivefold) improves the maximum velocity of PC activation by the thrombin-TM complex, explaining the basis for the proband's negative VTE pedigree. 25651845 3 52 theme antigen 523:529 arg1 level 531:535 PC antigen level 520:535 PC antigen level of 65% 520:542 A recent cohort study aimed at establishing a normal PC range identified a healthy PC-deficient subject whose PC antigen level of 65% and activity levels of 50% (chromogenic assay) and 36% (clotting assay) were markedly low. 25651845 5 53 theme heavy 787:791 arg1 chain 793:797 the PC heavy chain 780:797 the PC heavy chain 780:797 Genetic analysis revealed the proband has a heterozygous missense mutation in which Thr-315 of the PC heavy chain has been substituted with Ala. 25651845 3 54 theme % 597:597 arg1 level 531:535 PC antigen level 520:535 PC antigen level of 65% 520:542 A recent cohort study aimed at establishing a normal PC range identified a healthy PC-deficient subject whose PC antigen level of 65% and activity levels of 50% (chromogenic assay) and 36% (clotting assay) were markedly low. 25651845 3 54 theme % 597:597 arg1 levels 557:562 activity levels 548:562 activity levels of 50% (chromogenic assay) and 36% (clotting assay) 548:614 A recent cohort study aimed at establishing a normal PC range identified a healthy PC-deficient subject whose PC antigen level of 65% and activity levels of 50% (chromogenic assay) and 36% (clotting assay) were markedly low. 25651845 1 55 theme coagulation 260:270 arg1 cascade 272:278 the coagulation cascade 256:278 the coagulation cascade 256:278 Protein C (PC) is a vitamin K-dependent plasma glycoprotein, which upon activation by thrombin in complex with thrombomodulin (TM), regulates the coagulation cascade through a feedback loop inhibition mechanism. 25651845 9 56 theme glycosylation 1282:1294 arg1 site 1296:1299 a consensus N-linked glycosylation site 1261:1299 a consensus N-linked glycosylation site for Asn-313 1261:1311 Sequence analysis revealed Thr-315 is a consensus N-linked glycosylation site for Asn-313 and that its elimination significantly (∼four- to fivefold) improves the maximum velocity of PC activation by the thrombin-TM complex, explaining the basis for the proband's negative VTE pedigree. 25651845 9 56 theme glycosylation 1282:1294 arg1 Thr-315 1250:1256 Thr-315 1250:1256 Thr-315 1250:1256 Sequence analysis revealed Thr-315 is a consensus N-linked glycosylation site for Asn-313 and that its elimination significantly (∼four- to fivefold) improves the maximum velocity of PC activation by the thrombin-TM complex, explaining the basis for the proband's negative VTE pedigree. 25651845 5 57 dep has 723:725 arg1 revealed 702:709 revealed 702:709 revealed 702:709 Genetic analysis revealed the proband has a heterozygous missense mutation in which Thr-315 of the PC heavy chain has been substituted with Ala. 25651845 5 58 theme chain 793:797 arg1 Thr-315 769:775 Thr-315 769:775 Thr-315 of the PC heavy chain 769:797 Genetic analysis revealed the proband has a heterozygous missense mutation in which Thr-315 of the PC heavy chain has been substituted with Ala. 25651845 4 59 theme VTE 680:682 arg1 history 669:675 a negative family history 651:675 a negative family history of VTE 651:682 The proband has a negative family history of VTE. 25651845 9 60 theme negative 1487:1494 arg1 pedigree 1500:1507 the proband's negative VTE pedigree 1473:1507 the proband's negative VTE pedigree 1473:1507 Sequence analysis revealed Thr-315 is a consensus N-linked glycosylation site for Asn-313 and that its elimination significantly (∼four- to fivefold) improves the maximum velocity of PC activation by the thrombin-TM complex, explaining the basis for the proband's negative VTE pedigree. 25651845 0 61 from deficiency 81:90 arg1 assays 106:111 diagnostic assays 95:111 diagnostic assays 95:111 Protein C Thr315Ala variant results in gain of function but manifests as type II deficiency in diagnostic assays. 25651845 3 62 theme activity 548:555 arg1 levels 557:562 activity levels 548:562 activity levels of 50% (chromogenic assay) and 36% (clotting assay) 548:614 A recent cohort study aimed at establishing a normal PC range identified a healthy PC-deficient subject whose PC antigen level of 65% and activity levels of 50% (chromogenic assay) and 36% (clotting assay) were markedly low. 25651845 1 63 with complex 212:218 arg1 TM 241:242 TM 241:242 TM 241:242 Protein C (PC) is a vitamin K-dependent plasma glycoprotein, which upon activation by thrombin in complex with thrombomodulin (TM), regulates the coagulation cascade through a feedback loop inhibition mechanism. 25651845 1 63 with complex 212:218 arg1 thrombomodulin 225:238 thrombomodulin 225:238 thrombomodulin (TM) 225:243 Protein C (PC) is a vitamin K-dependent plasma glycoprotein, which upon activation by thrombin in complex with thrombomodulin (TM), regulates the coagulation cascade through a feedback loop inhibition mechanism. 25651845 3 64 theme cohort 419:424 arg1 study 426:430 A recent cohort study 410:430 A recent cohort study aimed at establishing a normal PC range 410:470 A recent cohort study aimed at establishing a normal PC range identified a healthy PC-deficient subject whose PC antigen level of 65% and activity levels of 50% (chromogenic assay) and 36% (clotting assay) were markedly low. 25651845 9 65 theme N-linked 1273:1280 arg1 site 1296:1299 a consensus N-linked glycosylation site 1261:1299 a consensus N-linked glycosylation site for Asn-313 1261:1311 Sequence analysis revealed Thr-315 is a consensus N-linked glycosylation site for Asn-313 and that its elimination significantly (∼four- to fivefold) improves the maximum velocity of PC activation by the thrombin-TM complex, explaining the basis for the proband's negative VTE pedigree. 25651845 9 65 theme N-linked 1273:1280 arg1 Thr-315 1250:1256 Thr-315 1250:1256 Thr-315 1250:1256 Sequence analysis revealed Thr-315 is a consensus N-linked glycosylation site for Asn-313 and that its elimination significantly (∼four- to fivefold) improves the maximum velocity of PC activation by the thrombin-TM complex, explaining the basis for the proband's negative VTE pedigree. 25651845 1 66 from activation 186:195 arg1 complex 212:218 complex 212:218 complex with thrombomodulin (TM) 212:243 Protein C (PC) is a vitamin K-dependent plasma glycoprotein, which upon activation by thrombin in complex with thrombomodulin (TM), regulates the coagulation cascade through a feedback loop inhibition mechanism. 25651845 3 67 theme chromogenic 572:582 arg1 % 569:569 50% 567:569 50% (chromogenic assay) 567:589 A recent cohort study aimed at establishing a normal PC range identified a healthy PC-deficient subject whose PC antigen level of 65% and activity levels of 50% (chromogenic assay) and 36% (clotting assay) were markedly low. 25651845 3 67 theme chromogenic 572:582 arg1 assay 584:588 chromogenic assay 572:588 chromogenic assay 572:588 A recent cohort study aimed at establishing a normal PC range identified a healthy PC-deficient subject whose PC antigen level of 65% and activity levels of 50% (chromogenic assay) and 36% (clotting assay) were markedly low. 25651845 1 68 theme Protein 114:120 arg1 glycoprotein 161:172 a vitamin K-dependent plasma glycoprotein 132:172 a vitamin K-dependent plasma glycoprotein 132:172 Protein C (PC) is a vitamin K-dependent plasma glycoprotein, which upon activation by thrombin in complex with thrombomodulin (TM), regulates the coagulation cascade through a feedback loop inhibition mechanism. 25651845 1 68 theme Protein 114:120 arg1 PC 125:126 PC 125:126 PC 125:126 Protein C (PC) is a vitamin K-dependent plasma glycoprotein, which upon activation by thrombin in complex with thrombomodulin (TM), regulates the coagulation cascade through a feedback loop inhibition mechanism. 25651845 1 68 theme Protein 114:120 arg1 C 122:122 Protein C 114:122 Protein C (PC) 114:127 Protein C (PC) is a vitamin K-dependent plasma glycoprotein, which upon activation by thrombin in complex with thrombomodulin (TM), regulates the coagulation cascade through a feedback loop inhibition mechanism. 25651845 8 69 theme improved 1188:1195 arg1 activities 1197:1206 improved activities 1188:1206 improved activities 1188:1206 Interestingly, we discovered if functional assays were coupled to PC activation by the thrombin-TM complex, the variant exhibits improved activities in all assays. 25651845 3 70 theme % 542:542 arg1 level 531:535 PC antigen level 520:535 PC antigen level of 65% 520:542 A recent cohort study aimed at establishing a normal PC range identified a healthy PC-deficient subject whose PC antigen level of 65% and activity levels of 50% (chromogenic assay) and 36% (clotting assay) were markedly low. 25651845 3 70 theme % 542:542 arg1 levels 557:562 activity levels 548:562 activity levels of 50% (chromogenic assay) and 36% (clotting assay) 548:614 A recent cohort study aimed at establishing a normal PC range identified a healthy PC-deficient subject whose PC antigen level of 65% and activity levels of 50% (chromogenic assay) and 36% (clotting assay) were markedly low. 25651845 8 71 theme thrombin-TM 1146:1156 arg1 complex 1158:1164 the thrombin-TM complex 1142:1164 the thrombin-TM complex 1142:1164 Interestingly, we discovered if functional assays were coupled to PC activation by the thrombin-TM complex, the variant exhibits improved activities in all assays. 25651845 2 72 theme PC 326:327 arg1 deficiency 329:338 PC deficiency 326:338 PC deficiency 326:338 PC deficiency is associated with an increased risk of venous thromboembolism (VTE). 25651845 7 73 from decrease 914:921 arg1 activities 967:976 both anticoagulant and anti-inflammatory activities 926:976 both anticoagulant and anti-inflammatory activities of the activated protein C mutant 926:1010 A similar decrease in both anticoagulant and anti-inflammatory activities of the activated protein C mutant was observed in plasma- and cell-based assays. 25651845 0 74 theme function 47:54 arg1 gain 39:42 gain 39:42 gain of function 39:54 Protein C Thr315Ala variant results in gain of function but manifests as type II deficiency in diagnostic assays. 25651845 0 75 theme Thr315Ala 10:18 arg1 variant 20:26 Protein C Thr315Ala variant 0:26 Protein C Thr315Ala variant 0:26 Protein C Thr315Ala variant results in gain of function but manifests as type II deficiency in diagnostic assays. 25651845 3 76 theme PC 463:464 arg1 range 466:470 a normal PC range 454:470 a normal PC range 454:470 A recent cohort study aimed at establishing a normal PC range identified a healthy PC-deficient subject whose PC antigen level of 65% and activity levels of 50% (chromogenic assay) and 36% (clotting assay) were markedly low. 25651845 9 77 theme VTE 1496:1498 arg1 pedigree 1500:1507 the proband's negative VTE pedigree 1473:1507 the proband's negative VTE pedigree 1473:1507 Sequence analysis revealed Thr-315 is a consensus N-linked glycosylation site for Asn-313 and that its elimination significantly (∼four- to fivefold) improves the maximum velocity of PC activation by the thrombin-TM complex, explaining the basis for the proband's negative VTE pedigree. 23763973 0 0 theme major 61:65 arg1 allergen 74:81 a major rabbit allergen 59:81 a major rabbit allergen 59:81 Identification and isolation of a Fel d 1-like molecule as a major rabbit allergen. 23763973 7 1 theme IgE 654:656 arg1 reactivity 658:667 IgE reactivity 654:667 IgE reactivity to a new allergen 654:685 IgE reactivity to a new allergen was analyzed in sera of 35 patients sensitized to rabbits in a domestic setting. 23763973 1 2 theme domestic 129:136 arg1 Rabbits 96:102 Rabbits 96:102 Rabbits 96:102 BACKGROUND: Rabbits are increasingly kept as domestic pets. 23763973 1 2 theme domestic 129:136 arg1 pets 138:141 domestic pets 129:141 domestic pets 129:141 BACKGROUND: Rabbits are increasingly kept as domestic pets. 23763973 8 3 theme isolated 808:815 arg1 proteins 817:824 the isolated proteins 804:824 the isolated proteins 804:824 A model of the crystal structure of the isolated proteins was constructed. 23763973 16 4 theme heterodimer 1574:1584 arg1 allergen 1631:1638 a major rabbit allergen 1616:1638 a major rabbit allergen 1616:1638 CONCLUSION: The rabbit lipophilin heterodimer AL-CL2 has been identified as a major rabbit allergen. 23763973 16 4 theme heterodimer 1574:1584 arg1 AL-CL2 1586:1591 The rabbit lipophilin heterodimer AL-CL2 1552:1591 The rabbit lipophilin heterodimer AL-CL2 1552:1591 CONCLUSION: The rabbit lipophilin heterodimer AL-CL2 has been identified as a major rabbit allergen. 23763973 17 5 theme Fel 1647:1649 arg1 d 1651:1651 Fel d 1 1647:1653 Fel d 1 1647:1653 After Fel d 1, Ory c 3 is the second mammalian secretoglobin shown to be a major allergen. 23763973 10 6 theme kDa 1010:1012 arg1 molecule 931:938 The molecule 927:938 The molecule that belongs to the secretoglobin family 927:979 The molecule that belongs to the secretoglobin family is a heterodimer of 18 to 19 kDa composed of 2 polypeptide chains, CL2 and AL. 23763973 10 6 theme kDa 1010:1012 arg1 heterodimer 986:996 a heterodimer 984:996 a heterodimer of 18 to 19 kDa composed of 2 polypeptide chains, CL2 and AL 984:1057 The molecule that belongs to the secretoglobin family is a heterodimer of 18 to 19 kDa composed of 2 polypeptide chains, CL2 and AL. 23763973 14 7 theme Fel 1432:1434 arg1 d 1436:1436 Fel d 1 1432:1438 Fel d 1 1432:1438 Modeling of the structure revealed a marked homology to Fel d 1, the major cat allergen. 23763973 14 7 theme Fel 1432:1434 arg1 allergen 1455:1462 the major cat allergen 1441:1462 the major cat allergen 1441:1462 Modeling of the structure revealed a marked homology to Fel d 1, the major cat allergen. 23763973 6 8 theme N-terminal 609:618 arg1 sequencing 620:629 N-terminal sequencing 609:629 N-terminal sequencing 609:629 Allergens were characterized by means of N-terminal sequencing and mass spectrometry. 23763973 7 9 theme patients 714:721 arg1 sera 703:706 sera 703:706 sera of 35 patients sensitized to rabbits in a domestic setting 703:765 IgE reactivity to a new allergen was analyzed in sera of 35 patients sensitized to rabbits in a domestic setting. 23763973 11 10 link N-linked 1080:1087 arg1 site 1103:1106 a predicted N-linked glycosylation site 1068:1106 a predicted N-linked glycosylation site confirmed by using mass spectrometry 1068:1143 CL2 has a predicted N-linked glycosylation site confirmed by using mass spectrometry. 23763973 17 11 theme second 1671:1676 arg1 c 1660:1660 Ory c 3 1656:1662 Ory c 3 1656:1662 After Fel d 1, Ory c 3 is the second mammalian secretoglobin shown to be a major allergen. 23763973 17 11 theme second 1671:1676 arg1 secretoglobin 1688:1700 the second mammalian secretoglobin 1667:1700 the second mammalian secretoglobin shown to be a major allergen 1667:1729 After Fel d 1, Ory c 3 is the second mammalian secretoglobin shown to be a major allergen. 23763973 11 12 gly glycosylation 1089:1101 arg2 site 1103:1106 a predicted N-linked glycosylation site 1068:1106 a predicted N-linked glycosylation site confirmed by using mass spectrometry 1068:1143 CL2 has a predicted N-linked glycosylation site confirmed by using mass spectrometry. 23763973 0 13 theme rabbit 67:72 arg1 allergen 74:81 a major rabbit allergen 59:81 a major rabbit allergen 59:81 Identification and isolation of a Fel d 1-like molecule as a major rabbit allergen. 23763973 17 14 theme mammalian 1678:1686 arg1 c 1660:1660 Ory c 3 1656:1662 Ory c 3 1656:1662 After Fel d 1, Ory c 3 is the second mammalian secretoglobin shown to be a major allergen. 23763973 17 14 theme mammalian 1678:1686 arg1 secretoglobin 1688:1700 the second mammalian secretoglobin 1667:1700 the second mammalian secretoglobin shown to be a major allergen 1667:1729 After Fel d 1, Ory c 3 is the second mammalian secretoglobin shown to be a major allergen. 23763973 15 15 theme Ory 1531:1533 arg1 c 1535:1535 Ory c 3 1531:1537 Ory c 3 1531:1537 However, no IgE cross-reactivity was detected between Fel d 1 and Ory c 3. 23763973 12 16 with patients 1156:1163 arg1 allergy 1177:1183 rabbit allergy 1170:1183 rabbit allergy 1170:1183 Of the 35 patients with rabbit allergy studied, 27 (77%) had IgE to both the glycosylated and deglycosylated Ory c 3 heterodimer. 23763973 9 17 theme new 854:856 arg1 lipophilin 915:924 rabbit lipophilin 908:924 rabbit lipophilin 908:924 RESULTS: A new IgE-reactive allergen, Ory c 3, was identified as rabbit lipophilin. 23763973 9 17 theme new 854:856 arg1 allergen 871:878 A new IgE-reactive allergen 852:878 A new IgE-reactive allergen 852:878 RESULTS: A new IgE-reactive allergen, Ory c 3, was identified as rabbit lipophilin. 23763973 9 17 theme new 854:856 arg1 c 885:885 Ory c 3 881:887 Ory c 3 881:887 RESULTS: A new IgE-reactive allergen, Ory c 3, was identified as rabbit lipophilin. 23763973 12 18 dep the 1219:1221 arg1 heterodimer 1263:1273 Ory c 3 heterodimer 1255:1273 Ory c 3 heterodimer 1255:1273 Of the 35 patients with rabbit allergy studied, 27 (77%) had IgE to both the glycosylated and deglycosylated Ory c 3 heterodimer. 23763973 9 19 theme rabbit 908:913 arg1 lipophilin 915:924 rabbit lipophilin 908:924 rabbit lipophilin 908:924 RESULTS: A new IgE-reactive allergen, Ory c 3, was identified as rabbit lipophilin. 23763973 9 19 theme rabbit 908:913 arg1 allergen 871:878 A new IgE-reactive allergen 852:878 A new IgE-reactive allergen 852:878 RESULTS: A new IgE-reactive allergen, Ory c 3, was identified as rabbit lipophilin. 23763973 10 20 theme polypeptide 1028:1038 arg1 AL 1056:1057 AL 1056:1057 AL 1056:1057 The molecule that belongs to the secretoglobin family is a heterodimer of 18 to 19 kDa composed of 2 polypeptide chains, CL2 and AL. 23763973 10 20 theme polypeptide 1028:1038 arg1 CL2 1048:1050 CL2 1048:1050 CL2 1048:1050 The molecule that belongs to the secretoglobin family is a heterodimer of 18 to 19 kDa composed of 2 polypeptide chains, CL2 and AL. 23763973 10 20 theme polypeptide 1028:1038 arg1 chains 1040:1045 2 polypeptide chains 1026:1045 2 polypeptide chains 1026:1045 The molecule that belongs to the secretoglobin family is a heterodimer of 18 to 19 kDa composed of 2 polypeptide chains, CL2 and AL. 23763973 12 21 contain had 1203:1205 arg1 27 1194:1195 27 1194:1195 27 1194:1195 Of the 35 patients with rabbit allergy studied, 27 (77%) had IgE to both the glycosylated and deglycosylated Ory c 3 heterodimer. 23763973 12 21 contain had 1203:1205 arg2 IgE 1207:1209 IgE 1207:1209 IgE 1207:1209 Of the 35 patients with rabbit allergy studied, 27 (77%) had IgE to both the glycosylated and deglycosylated Ory c 3 heterodimer. 23763973 12 21 contain had 1203:1205 arg1 % 1200:1200 77% 1198:1200 77% 1198:1200 Of the 35 patients with rabbit allergy studied, 27 (77%) had IgE to both the glycosylated and deglycosylated Ory c 3 heterodimer. 23763973 5 22 theme sequential 541:550 arg1 chromatography 552:565 sequential chromatography 541:565 sequential chromatography 541:565 METHODS: Proteins were extracted from rabbit hair, and IgE-reactive proteins were purified by using sequential chromatography. 23763973 11 23 theme glycosylation 1089:1101 arg1 site 1103:1106 a predicted N-linked glycosylation site 1068:1106 a predicted N-linked glycosylation site confirmed by using mass spectrometry 1068:1143 CL2 has a predicted N-linked glycosylation site confirmed by using mass spectrometry. 23763973 5 24 theme rabbit 479:484 arg1 hair 486:489 rabbit hair 479:489 rabbit hair 479:489 METHODS: Proteins were extracted from rabbit hair, and IgE-reactive proteins were purified by using sequential chromatography. 23763973 11 25 contain has 1064:1066 arg1 CL2 1060:1062 CL2 1060:1062 CL2 1060:1062 CL2 has a predicted N-linked glycosylation site confirmed by using mass spectrometry. 23763973 11 25 contain has 1064:1066 arg2 site 1103:1106 a predicted N-linked glycosylation site 1068:1106 a predicted N-linked glycosylation site confirmed by using mass spectrometry 1068:1143 CL2 has a predicted N-linked glycosylation site confirmed by using mass spectrometry. 23763973 4 26 theme major 327:331 arg1 allergens 333:341 major allergens 327:341 major allergens 327:341 OBJECTIVE: We sought to isolate major allergens from the rabbit Oryctolagus cuniculus and to investigate their importance in sensitized patients. 23763973 11 27 theme mass 1127:1130 arg1 spectrometry 1132:1143 mass spectrometry 1127:1143 mass spectrometry 1127:1143 CL2 has a predicted N-linked glycosylation site confirmed by using mass spectrometry. 23763973 17 28 theme Ory 1656:1658 arg1 c 1660:1660 Ory c 3 1656:1662 Ory c 3 1656:1662 After Fel d 1, Ory c 3 is the second mammalian secretoglobin shown to be a major allergen. 23763973 17 28 theme Ory 1656:1658 arg1 secretoglobin 1688:1700 the second mammalian secretoglobin 1667:1700 the second mammalian secretoglobin shown to be a major allergen 1667:1729 After Fel d 1, Ory c 3 is the second mammalian secretoglobin shown to be a major allergen. 23763973 17 29 theme major 1716:1720 arg1 allergen 1722:1729 a major allergen 1714:1729 a major allergen 1714:1729 After Fel d 1, Ory c 3 is the second mammalian secretoglobin shown to be a major allergen. 23763973 14 30 theme structure 1392:1400 arg1 Modeling 1376:1383 Modeling 1376:1383 Modeling of the structure 1376:1400 Modeling of the structure revealed a marked homology to Fel d 1, the major cat allergen. 23763973 12 31 theme c 1259:1259 arg1 heterodimer 1263:1273 Ory c 3 heterodimer 1255:1273 Ory c 3 heterodimer 1255:1273 Of the 35 patients with rabbit allergy studied, 27 (77%) had IgE to both the glycosylated and deglycosylated Ory c 3 heterodimer. 23763973 15 32 theme Fel 1519:1521 arg1 d 1523:1523 Fel d 1 1519:1525 Fel d 1 1519:1525 However, no IgE cross-reactivity was detected between Fel d 1 and Ory c 3. 23763973 14 33 theme marked 1413:1418 arg1 homology 1420:1427 a marked homology 1411:1427 a marked homology to Fel d 1, the major cat allergen 1411:1462 Modeling of the structure revealed a marked homology to Fel d 1, the major cat allergen. 23763973 13 34 theme Ory 1293:1295 arg1 c 1297:1297 Ory c 3 1293:1299 Ory c 3 1293:1299 Allergenicity of Ory c 3 was confirmed by using skin prick tests and the basophil activation assay. 23763973 11 35 theme N-linked 1080:1087 arg1 site 1103:1106 a predicted N-linked glycosylation site 1068:1106 a predicted N-linked glycosylation site confirmed by using mass spectrometry 1068:1143 CL2 has a predicted N-linked glycosylation site confirmed by using mass spectrometry. 23763973 4 36 theme sensitized 420:429 arg1 patients 431:438 sensitized patients 420:438 sensitized patients 420:438 OBJECTIVE: We sought to isolate major allergens from the rabbit Oryctolagus cuniculus and to investigate their importance in sensitized patients. 23763973 0 37 theme Fel 34:36 arg1 molecule 47:54 a Fel d 1-like molecule 32:54 a Fel d 1-like molecule as a major rabbit allergen 32:81 Identification and isolation of a Fel d 1-like molecule as a major rabbit allergen. 23763973 13 38 theme c 1297:1297 arg1 Allergenicity 1276:1288 Allergenicity 1276:1288 Allergenicity of Ory c 3 1276:1299 Allergenicity of Ory c 3 was confirmed by using skin prick tests and the basophil activation assay. 23763973 2 39 theme rabbit 152:157 arg1 allergens 159:167 Several rabbit allergens 144:167 Several rabbit allergens 144:167 Several rabbit allergens have been characterized. 23763973 13 40 theme basophil 1349:1356 arg1 assay 1369:1373 the basophil activation assay 1345:1373 the basophil activation assay 1345:1373 Allergenicity of Ory c 3 was confirmed by using skin prick tests and the basophil activation assay. 23763973 16 41 theme rabbit 1624:1629 arg1 AL-CL2 1586:1591 The rabbit lipophilin heterodimer AL-CL2 1552:1591 The rabbit lipophilin heterodimer AL-CL2 1552:1591 CONCLUSION: The rabbit lipophilin heterodimer AL-CL2 has been identified as a major rabbit allergen. 23763973 16 41 theme rabbit 1624:1629 arg1 allergen 1631:1638 a major rabbit allergen 1616:1638 a major rabbit allergen 1616:1638 CONCLUSION: The rabbit lipophilin heterodimer AL-CL2 has been identified as a major rabbit allergen. 23763973 16 42 theme lipophilin 1563:1572 arg1 allergen 1631:1638 a major rabbit allergen 1616:1638 a major rabbit allergen 1616:1638 CONCLUSION: The rabbit lipophilin heterodimer AL-CL2 has been identified as a major rabbit allergen. 23763973 16 42 theme lipophilin 1563:1572 arg1 AL-CL2 1586:1591 The rabbit lipophilin heterodimer AL-CL2 1552:1591 The rabbit lipophilin heterodimer AL-CL2 1552:1591 CONCLUSION: The rabbit lipophilin heterodimer AL-CL2 has been identified as a major rabbit allergen. 23763973 2 43 theme Several 144:150 arg1 allergens 159:167 Several rabbit allergens 144:167 Several rabbit allergens 144:167 Several rabbit allergens have been characterized. 23763973 13 44 theme activation 1358:1367 arg1 assay 1369:1373 the basophil activation assay 1345:1373 the basophil activation assay 1345:1373 Allergenicity of Ory c 3 was confirmed by using skin prick tests and the basophil activation assay. 23763973 0 45 theme 1-like 40:45 arg1 molecule 47:54 a Fel d 1-like molecule 32:54 a Fel d 1-like molecule as a major rabbit allergen 32:81 Identification and isolation of a Fel d 1-like molecule as a major rabbit allergen. 23763973 10 46 dep 19 1007:1008 arg1 to 1004:1005 to 1004:1005 to 1004:1005 The molecule that belongs to the secretoglobin family is a heterodimer of 18 to 19 kDa composed of 2 polypeptide chains, CL2 and AL. 23763973 4 47 from importance 406:415 arg1 patients 431:438 sensitized patients 420:438 sensitized patients 420:438 OBJECTIVE: We sought to isolate major allergens from the rabbit Oryctolagus cuniculus and to investigate their importance in sensitized patients. 23763973 10 48 theme secretoglobin 960:972 arg1 family 974:979 the secretoglobin family 956:979 the secretoglobin family 956:979 The molecule that belongs to the secretoglobin family is a heterodimer of 18 to 19 kDa composed of 2 polypeptide chains, CL2 and AL. 23763973 12 49 theme Ory 1255:1257 arg1 heterodimer 1263:1273 Ory c 3 heterodimer 1255:1273 Ory c 3 heterodimer 1255:1273 Of the 35 patients with rabbit allergy studied, 27 (77%) had IgE to both the glycosylated and deglycosylated Ory c 3 heterodimer. 23763973 0 50 theme d 38:38 arg1 molecule 47:54 a Fel d 1-like molecule 32:54 a Fel d 1-like molecule as a major rabbit allergen 32:81 Identification and isolation of a Fel d 1-like molecule as a major rabbit allergen. 23763973 9 51 theme IgE-reactive 858:869 arg1 lipophilin 915:924 rabbit lipophilin 908:924 rabbit lipophilin 908:924 RESULTS: A new IgE-reactive allergen, Ory c 3, was identified as rabbit lipophilin. 23763973 9 51 theme IgE-reactive 858:869 arg1 allergen 871:878 A new IgE-reactive allergen 852:878 A new IgE-reactive allergen 852:878 RESULTS: A new IgE-reactive allergen, Ory c 3, was identified as rabbit lipophilin. 23763973 9 51 theme IgE-reactive 858:869 arg1 c 885:885 Ory c 3 881:887 Ory c 3 881:887 RESULTS: A new IgE-reactive allergen, Ory c 3, was identified as rabbit lipophilin. 23763973 14 52 theme cat 1451:1453 arg1 d 1436:1436 Fel d 1 1432:1438 Fel d 1 1432:1438 Modeling of the structure revealed a marked homology to Fel d 1, the major cat allergen. 23763973 14 52 theme cat 1451:1453 arg1 allergen 1455:1462 the major cat allergen 1441:1462 the major cat allergen 1441:1462 Modeling of the structure revealed a marked homology to Fel d 1, the major cat allergen. 23763973 13 53 theme skin 1324:1327 arg1 tests 1335:1339 skin prick tests 1324:1339 skin prick tests 1324:1339 Allergenicity of Ory c 3 was confirmed by using skin prick tests and the basophil activation assay. 23763973 8 54 theme structure 791:799 arg1 model 770:774 A model 768:774 A model of the crystal structure of the isolated proteins 768:824 A model of the crystal structure of the isolated proteins was constructed. 23763973 7 55 theme domestic 750:757 arg1 setting 759:765 a domestic setting 748:765 a domestic setting 748:765 IgE reactivity to a new allergen was analyzed in sera of 35 patients sensitized to rabbits in a domestic setting. 23763973 7 56 theme new 674:676 arg1 allergen 678:685 a new allergen 672:685 a new allergen 672:685 IgE reactivity to a new allergen was analyzed in sera of 35 patients sensitized to rabbits in a domestic setting. 23763973 14 57 theme major 1445:1449 arg1 d 1436:1436 Fel d 1 1432:1438 Fel d 1 1432:1438 Modeling of the structure revealed a marked homology to Fel d 1, the major cat allergen. 23763973 14 57 theme major 1445:1449 arg1 allergen 1455:1462 the major cat allergen 1441:1462 the major cat allergen 1441:1462 Modeling of the structure revealed a marked homology to Fel d 1, the major cat allergen. 23763973 13 58 theme prick 1329:1333 arg1 tests 1335:1339 skin prick tests 1324:1339 skin prick tests 1324:1339 Allergenicity of Ory c 3 was confirmed by using skin prick tests and the basophil activation assay. 23763973 8 59 theme crystal 783:789 arg1 structure 791:799 the crystal structure 779:799 the crystal structure of the isolated proteins 779:824 A model of the crystal structure of the isolated proteins was constructed. 23763973 11 60 theme predicted 1070:1078 arg1 site 1103:1106 a predicted N-linked glycosylation site 1068:1106 a predicted N-linked glycosylation site confirmed by using mass spectrometry 1068:1143 CL2 has a predicted N-linked glycosylation site confirmed by using mass spectrometry. 23763973 12 61 theme rabbit 1170:1175 arg1 allergy 1177:1183 rabbit allergy 1170:1183 rabbit allergy 1170:1183 Of the 35 patients with rabbit allergy studied, 27 (77%) had IgE to both the glycosylated and deglycosylated Ory c 3 heterodimer. 23763973 9 62 theme Ory 881:883 arg1 allergen 871:878 A new IgE-reactive allergen 852:878 A new IgE-reactive allergen 852:878 RESULTS: A new IgE-reactive allergen, Ory c 3, was identified as rabbit lipophilin. 23763973 9 62 theme Ory 881:883 arg1 c 885:885 Ory c 3 881:887 Ory c 3 881:887 RESULTS: A new IgE-reactive allergen, Ory c 3, was identified as rabbit lipophilin. 23763973 15 63 theme IgE 1477:1479 arg1 cross-reactivity 1481:1496 no IgE cross-reactivity 1474:1496 no IgE cross-reactivity 1474:1496 However, no IgE cross-reactivity was detected between Fel d 1 and Ory c 3. 23763973 6 64 theme mass 635:638 arg1 spectrometry 640:651 mass spectrometry 635:651 mass spectrometry 635:651 Allergens were characterized by means of N-terminal sequencing and mass spectrometry. 23763973 16 65 theme rabbit 1556:1561 arg1 allergen 1631:1638 a major rabbit allergen 1616:1638 a major rabbit allergen 1616:1638 CONCLUSION: The rabbit lipophilin heterodimer AL-CL2 has been identified as a major rabbit allergen. 23763973 16 65 theme rabbit 1556:1561 arg1 AL-CL2 1586:1591 The rabbit lipophilin heterodimer AL-CL2 1552:1591 The rabbit lipophilin heterodimer AL-CL2 1552:1591 CONCLUSION: The rabbit lipophilin heterodimer AL-CL2 has been identified as a major rabbit allergen. 23763973 0 66 theme molecule 47:54 arg1 isolation 19:27 isolation 19:27 isolation 19:27 Identification and isolation of a Fel d 1-like molecule as a major rabbit allergen. 23763973 0 66 theme molecule 47:54 arg1 Identification 0:13 Identification 0:13 Identification 0:13 Identification and isolation of a Fel d 1-like molecule as a major rabbit allergen. 23763973 5 67 theme IgE-reactive 496:507 arg1 proteins 509:516 IgE-reactive proteins 496:516 IgE-reactive proteins 496:516 METHODS: Proteins were extracted from rabbit hair, and IgE-reactive proteins were purified by using sequential chromatography. 23763973 8 68 theme proteins 817:824 arg1 structure 791:799 the crystal structure 779:799 the crystal structure of the isolated proteins 779:824 A model of the crystal structure of the isolated proteins was constructed. 23763973 16 69 theme major 1618:1622 arg1 AL-CL2 1586:1591 The rabbit lipophilin heterodimer AL-CL2 1552:1591 The rabbit lipophilin heterodimer AL-CL2 1552:1591 CONCLUSION: The rabbit lipophilin heterodimer AL-CL2 has been identified as a major rabbit allergen. 23763973 16 69 theme major 1618:1622 arg1 allergen 1631:1638 a major rabbit allergen 1616:1638 a major rabbit allergen 1616:1638 CONCLUSION: The rabbit lipophilin heterodimer AL-CL2 has been identified as a major rabbit allergen. 24369354 6 0 theme great 1001:1005 arg1 challenge 1007:1015 a great challenge 999:1015 a great challenge to our future preventative and therapeutic interventions based on VRC01 999:1087 The persistence and continuing evolution of VRC01-resistant HIV-1 in vivo presents a great challenge to our future preventative and therapeutic interventions based on VRC01. 24369354 6 1 theme preventative 1031:1042 arg1 interventions 1060:1072 our future preventative and therapeutic interventions 1020:1072 our future preventative and therapeutic interventions based on VRC01 1020:1087 The persistence and continuing evolution of VRC01-resistant HIV-1 in vivo presents a great challenge to our future preventative and therapeutic interventions based on VRC01. 24369354 1 2 theme diverse 144:150 arg1 array 152:156 a diverse array 142:156 a diverse array of HIV-1 isolates 142:174 VRC01, a broadly neutralizing monoclonal antibody (bnmAb), can neutralize a diverse array of HIV-1 isolates by mimicking CD4 binding to the envelope glycoprotein gp120. 24369354 4 3 theme VRC01-resistant 565:579 arg1 HIV-1 581:585 VRC01-resistant HIV-1 565:585 VRC01-resistant HIV-1 565:585 With genetic and phenotypic analysis of over 70 full-length molecular clones of the HIV-1 envelope, we show that VRC01-resistant HIV-1 continued to exist and change in its proportion of the infecting virus during treatment with a highly active antiretroviral therapy. 24369354 5 4 theme resistant 766:774 arg1 phenotype 776:784 the resistant phenotype 762:784 the resistant phenotype 762:784 Consistent with our previous observation, the resistant phenotype was associated with a single asparagine residue at position 460 (N460), a potential N-linked glycosylation site in the V5 region. 24369354 4 5 theme molecular 512:520 arg1 clones 522:527 over 70 full-length molecular clones 492:527 over 70 full-length molecular clones of the HIV-1 envelope 492:549 With genetic and phenotypic analysis of over 70 full-length molecular clones of the HIV-1 envelope, we show that VRC01-resistant HIV-1 continued to exist and change in its proportion of the infecting virus during treatment with a highly active antiretroviral therapy. 24369354 2 6 theme antiretroviral 345:358 arg1 therapy 360:366 antiretroviral therapy 345:366 antiretroviral therapy 345:366 We have previously demonstrated the presence of VRC01-resistant strains in an HIV-1 infected patient during antiretroviral therapy. 24369354 4 7 theme full-length 500:510 arg1 clones 522:527 over 70 full-length molecular clones 492:527 over 70 full-length molecular clones of the HIV-1 envelope 492:549 With genetic and phenotypic analysis of over 70 full-length molecular clones of the HIV-1 envelope, we show that VRC01-resistant HIV-1 continued to exist and change in its proportion of the infecting virus during treatment with a highly active antiretroviral therapy. 24369354 5 8 from site 893:896 arg1 region 908:913 the V5 region 901:913 the V5 region 901:913 Consistent with our previous observation, the resistant phenotype was associated with a single asparagine residue at position 460 (N460), a potential N-linked glycosylation site in the V5 region. 24369354 4 9 theme phenotypic 469:478 arg1 analysis 480:487 genetic and phenotypic analysis 457:487 genetic and phenotypic analysis of over 70 full-length molecular clones of the HIV-1 envelope 457:549 With genetic and phenotypic analysis of over 70 full-length molecular clones of the HIV-1 envelope, we show that VRC01-resistant HIV-1 continued to exist and change in its proportion of the infecting virus during treatment with a highly active antiretroviral therapy. 24369354 5 10 theme glycosylation 879:891 arg1 site 893:896 a potential N-linked glycosylation site 858:896 a potential N-linked glycosylation site in the V5 region 858:913 Consistent with our previous observation, the resistant phenotype was associated with a single asparagine residue at position 460 (N460), a potential N-linked glycosylation site in the V5 region. 24369354 5 10 theme glycosylation 879:891 arg1 position 837:844 position 460 837:848 position 460 (N460) 837:855 Consistent with our previous observation, the resistant phenotype was associated with a single asparagine residue at position 460 (N460), a potential N-linked glycosylation site in the V5 region. 24369354 6 11 theme HIV-1 976:980 arg1 persistence 920:930 persistence 920:930 persistence 920:930 The persistence and continuing evolution of VRC01-resistant HIV-1 in vivo presents a great challenge to our future preventative and therapeutic interventions based on VRC01. 24369354 6 11 theme HIV-1 976:980 arg1 evolution 947:955 continuing evolution 936:955 continuing evolution 936:955 The persistence and continuing evolution of VRC01-resistant HIV-1 in vivo presents a great challenge to our future preventative and therapeutic interventions based on VRC01. 24369354 1 12 gly glycoprotein 217:228 arg1 glycoprotein 217:228 the envelope glycoprotein gp120 204:234 the envelope glycoprotein gp120 204:234 VRC01, a broadly neutralizing monoclonal antibody (bnmAb), can neutralize a diverse array of HIV-1 isolates by mimicking CD4 binding to the envelope glycoprotein gp120. 24369354 1 13 theme isolates 167:174 arg1 array 152:156 a diverse array 142:156 a diverse array of HIV-1 isolates 142:174 VRC01, a broadly neutralizing monoclonal antibody (bnmAb), can neutralize a diverse array of HIV-1 isolates by mimicking CD4 binding to the envelope glycoprotein gp120. 24369354 4 14 theme infecting 642:650 arg1 virus 652:656 the infecting virus 638:656 the infecting virus 638:656 With genetic and phenotypic analysis of over 70 full-length molecular clones of the HIV-1 envelope, we show that VRC01-resistant HIV-1 continued to exist and change in its proportion of the infecting virus during treatment with a highly active antiretroviral therapy. 24369354 5 15 theme previous 740:747 arg1 observation 749:759 our previous observation 736:759 our previous observation 736:759 Consistent with our previous observation, the resistant phenotype was associated with a single asparagine residue at position 460 (N460), a potential N-linked glycosylation site in the V5 region. 24369354 1 16 theme broadly 77:83 arg1 bnmAb 119:123 bnmAb 119:123 bnmAb 119:123 VRC01, a broadly neutralizing monoclonal antibody (bnmAb), can neutralize a diverse array of HIV-1 isolates by mimicking CD4 binding to the envelope glycoprotein gp120. 24369354 1 16 theme broadly 77:83 arg1 antibody 109:116 a broadly neutralizing monoclonal antibody 75:116 a broadly neutralizing monoclonal antibody (bnmAb) 75:124 VRC01, a broadly neutralizing monoclonal antibody (bnmAb), can neutralize a diverse array of HIV-1 isolates by mimicking CD4 binding to the envelope glycoprotein gp120. 24369354 1 16 theme broadly 77:83 arg1 VRC01 68:72 VRC01 68:72 VRC01 68:72 VRC01, a broadly neutralizing monoclonal antibody (bnmAb), can neutralize a diverse array of HIV-1 isolates by mimicking CD4 binding to the envelope glycoprotein gp120. 24369354 1 17 theme HIV-1 161:165 arg1 isolates 167:174 HIV-1 isolates 161:174 HIV-1 isolates 161:174 VRC01, a broadly neutralizing monoclonal antibody (bnmAb), can neutralize a diverse array of HIV-1 isolates by mimicking CD4 binding to the envelope glycoprotein gp120. 24369354 4 18 with treatment 665:673 arg1 therapy 711:717 a highly active antiretroviral therapy 680:717 a highly active antiretroviral therapy 680:717 With genetic and phenotypic analysis of over 70 full-length molecular clones of the HIV-1 envelope, we show that VRC01-resistant HIV-1 continued to exist and change in its proportion of the infecting virus during treatment with a highly active antiretroviral therapy. 24369354 1 19 theme neutralizing 85:96 arg1 bnmAb 119:123 bnmAb 119:123 bnmAb 119:123 VRC01, a broadly neutralizing monoclonal antibody (bnmAb), can neutralize a diverse array of HIV-1 isolates by mimicking CD4 binding to the envelope glycoprotein gp120. 24369354 1 19 theme neutralizing 85:96 arg1 antibody 109:116 a broadly neutralizing monoclonal antibody 75:116 a broadly neutralizing monoclonal antibody (bnmAb) 75:124 VRC01, a broadly neutralizing monoclonal antibody (bnmAb), can neutralize a diverse array of HIV-1 isolates by mimicking CD4 binding to the envelope glycoprotein gp120. 24369354 1 19 theme neutralizing 85:96 arg1 VRC01 68:72 VRC01 68:72 VRC01 68:72 VRC01, a broadly neutralizing monoclonal antibody (bnmAb), can neutralize a diverse array of HIV-1 isolates by mimicking CD4 binding to the envelope glycoprotein gp120. 24369354 3 20 theme samples 421:427 arg1 studies 395:401 follow-up studies 385:401 follow-up studies of two subsequent samples from the same patient 385:449 Here, we report follow-up studies of two subsequent samples from the same patient. 24369354 3 21 theme follow-up 385:393 arg1 studies 395:401 follow-up studies 385:401 follow-up studies of two subsequent samples from the same patient 385:449 Here, we report follow-up studies of two subsequent samples from the same patient. 24369354 6 22 theme VRC01-resistant 960:974 arg1 HIV-1 976:980 VRC01-resistant HIV-1 960:980 VRC01-resistant HIV-1 960:980 The persistence and continuing evolution of VRC01-resistant HIV-1 in vivo presents a great challenge to our future preventative and therapeutic interventions based on VRC01. 24369354 1 23 theme monoclonal 98:107 arg1 bnmAb 119:123 bnmAb 119:123 bnmAb 119:123 VRC01, a broadly neutralizing monoclonal antibody (bnmAb), can neutralize a diverse array of HIV-1 isolates by mimicking CD4 binding to the envelope glycoprotein gp120. 24369354 1 23 theme monoclonal 98:107 arg1 antibody 109:116 a broadly neutralizing monoclonal antibody 75:116 a broadly neutralizing monoclonal antibody (bnmAb) 75:124 VRC01, a broadly neutralizing monoclonal antibody (bnmAb), can neutralize a diverse array of HIV-1 isolates by mimicking CD4 binding to the envelope glycoprotein gp120. 24369354 1 23 theme monoclonal 98:107 arg1 VRC01 68:72 VRC01 68:72 VRC01 68:72 VRC01, a broadly neutralizing monoclonal antibody (bnmAb), can neutralize a diverse array of HIV-1 isolates by mimicking CD4 binding to the envelope glycoprotein gp120. 24369354 4 24 theme virus 652:656 arg1 proportion 624:633 its proportion 620:633 its proportion of the infecting virus 620:656 With genetic and phenotypic analysis of over 70 full-length molecular clones of the HIV-1 envelope, we show that VRC01-resistant HIV-1 continued to exist and change in its proportion of the infecting virus during treatment with a highly active antiretroviral therapy. 24369354 0 25 theme HIV-1 31:35 arg1 Persistence 0:10 Persistence 0:10 Persistence of VRC01-resistant HIV-1 during antiretroviral therapy 0:65 Persistence of VRC01-resistant HIV-1 during antiretroviral therapy. 24369354 4 26 theme envelope 542:549 arg1 clones 522:527 over 70 full-length molecular clones 492:527 over 70 full-length molecular clones of the HIV-1 envelope 492:549 With genetic and phenotypic analysis of over 70 full-length molecular clones of the HIV-1 envelope, we show that VRC01-resistant HIV-1 continued to exist and change in its proportion of the infecting virus during treatment with a highly active antiretroviral therapy. 24369354 2 27 theme strains 301:307 arg1 presence 273:280 the presence 269:280 the presence of VRC01-resistant strains in an HIV-1 infected patient during antiretroviral therapy 269:366 We have previously demonstrated the presence of VRC01-resistant strains in an HIV-1 infected patient during antiretroviral therapy. 24369354 0 28 theme VRC01-resistant 15:29 arg1 HIV-1 31:35 VRC01-resistant HIV-1 15:35 VRC01-resistant HIV-1 15:35 Persistence of VRC01-resistant HIV-1 during antiretroviral therapy. 24369354 5 29 theme V5 905:906 arg1 region 908:913 the V5 region 901:913 the V5 region 901:913 Consistent with our previous observation, the resistant phenotype was associated with a single asparagine residue at position 460 (N460), a potential N-linked glycosylation site in the V5 region. 24369354 2 30 theme VRC01-resistant 285:299 arg1 strains 301:307 VRC01-resistant strains 285:307 VRC01-resistant strains 285:307 We have previously demonstrated the presence of VRC01-resistant strains in an HIV-1 infected patient during antiretroviral therapy. 24369354 1 31 theme CD4 189:191 arg1 binding 193:199 CD4 binding 189:199 CD4 binding to the envelope glycoprotein gp120 189:234 VRC01, a broadly neutralizing monoclonal antibody (bnmAb), can neutralize a diverse array of HIV-1 isolates by mimicking CD4 binding to the envelope glycoprotein gp120. 24369354 0 32 theme antiretroviral 44:57 arg1 therapy 59:65 antiretroviral therapy 44:65 antiretroviral therapy 44:65 Persistence of VRC01-resistant HIV-1 during antiretroviral therapy. 24369354 6 33 theme continuing 936:945 arg1 evolution 947:955 continuing evolution 936:955 continuing evolution 936:955 The persistence and continuing evolution of VRC01-resistant HIV-1 in vivo presents a great challenge to our future preventative and therapeutic interventions based on VRC01. 24369354 6 34 theme therapeutic 1048:1058 arg1 interventions 1060:1072 our future preventative and therapeutic interventions 1020:1072 our future preventative and therapeutic interventions based on VRC01 1020:1087 The persistence and continuing evolution of VRC01-resistant HIV-1 in vivo presents a great challenge to our future preventative and therapeutic interventions based on VRC01. 24369354 6 35 theme future 1024:1029 arg1 interventions 1060:1072 our future preventative and therapeutic interventions 1020:1072 our future preventative and therapeutic interventions based on VRC01 1020:1087 The persistence and continuing evolution of VRC01-resistant HIV-1 in vivo presents a great challenge to our future preventative and therapeutic interventions based on VRC01. 24369354 3 36 theme subsequent 410:419 arg1 samples 421:427 two subsequent samples 406:427 two subsequent samples from the same patient 406:449 Here, we report follow-up studies of two subsequent samples from the same patient. 24369354 2 37 attach presence 273:280 arg1 patient 330:336 an HIV-1 infected patient 312:336 an HIV-1 infected patient during antiretroviral therapy 312:366 We have previously demonstrated the presence of VRC01-resistant strains in an HIV-1 infected patient during antiretroviral therapy. 24369354 2 37 attach presence 273:280 arg2 strains 301:307 VRC01-resistant strains 285:307 VRC01-resistant strains 285:307 We have previously demonstrated the presence of VRC01-resistant strains in an HIV-1 infected patient during antiretroviral therapy. 24369354 5 38 link N-linked 870:877 arg1 site 893:896 a potential N-linked glycosylation site 858:896 a potential N-linked glycosylation site in the V5 region 858:913 Consistent with our previous observation, the resistant phenotype was associated with a single asparagine residue at position 460 (N460), a potential N-linked glycosylation site in the V5 region. 24369354 5 38 link N-linked 870:877 arg1 position 837:844 position 460 837:848 position 460 (N460) 837:855 Consistent with our previous observation, the resistant phenotype was associated with a single asparagine residue at position 460 (N460), a potential N-linked glycosylation site in the V5 region. 24369354 4 39 theme genetic 457:463 arg1 analysis 480:487 genetic and phenotypic analysis 457:487 genetic and phenotypic analysis of over 70 full-length molecular clones of the HIV-1 envelope 457:549 With genetic and phenotypic analysis of over 70 full-length molecular clones of the HIV-1 envelope, we show that VRC01-resistant HIV-1 continued to exist and change in its proportion of the infecting virus during treatment with a highly active antiretroviral therapy. 24369354 5 40 theme asparagine 815:824 arg1 residue 826:832 a single asparagine residue 806:832 a single asparagine residue at position 460 (N460), a potential N-linked glycosylation site in the V5 region 806:913 Consistent with our previous observation, the resistant phenotype was associated with a single asparagine residue at position 460 (N460), a potential N-linked glycosylation site in the V5 region. 24369354 3 41 from patient 443:449 arg1 samples 421:427 two subsequent samples 406:427 two subsequent samples from the same patient 406:449 Here, we report follow-up studies of two subsequent samples from the same patient. 24369354 3 41 from patient 443:449 arg1 studies 395:401 follow-up studies 385:401 follow-up studies of two subsequent samples from the same patient 385:449 Here, we report follow-up studies of two subsequent samples from the same patient. 24369354 4 42 theme clones 522:527 arg1 analysis 480:487 genetic and phenotypic analysis 457:487 genetic and phenotypic analysis of over 70 full-length molecular clones of the HIV-1 envelope 457:549 With genetic and phenotypic analysis of over 70 full-length molecular clones of the HIV-1 envelope, we show that VRC01-resistant HIV-1 continued to exist and change in its proportion of the infecting virus during treatment with a highly active antiretroviral therapy. 24369354 6 43 dep persistence 920:930 arg1 The 916:918 The 916:918 The 916:918 The persistence and continuing evolution of VRC01-resistant HIV-1 in vivo presents a great challenge to our future preventative and therapeutic interventions based on VRC01. 24369354 5 44 with Consistent 720:729 arg1 observation 749:759 our previous observation 736:759 our previous observation 736:759 Consistent with our previous observation, the resistant phenotype was associated with a single asparagine residue at position 460 (N460), a potential N-linked glycosylation site in the V5 region. 24369354 4 45 theme antiretroviral 696:709 arg1 therapy 711:717 a highly active antiretroviral therapy 680:717 a highly active antiretroviral therapy 680:717 With genetic and phenotypic analysis of over 70 full-length molecular clones of the HIV-1 envelope, we show that VRC01-resistant HIV-1 continued to exist and change in its proportion of the infecting virus during treatment with a highly active antiretroviral therapy. 24369354 4 46 theme HIV-1 536:540 arg1 envelope 542:549 the HIV-1 envelope 532:549 the HIV-1 envelope 532:549 With genetic and phenotypic analysis of over 70 full-length molecular clones of the HIV-1 envelope, we show that VRC01-resistant HIV-1 continued to exist and change in its proportion of the infecting virus during treatment with a highly active antiretroviral therapy. 24369354 4 47 theme active 689:694 arg1 therapy 711:717 a highly active antiretroviral therapy 680:717 a highly active antiretroviral therapy 680:717 With genetic and phenotypic analysis of over 70 full-length molecular clones of the HIV-1 envelope, we show that VRC01-resistant HIV-1 continued to exist and change in its proportion of the infecting virus during treatment with a highly active antiretroviral therapy. 24369354 5 48 from position 837:844 arg1 residue 826:832 a single asparagine residue 806:832 a single asparagine residue at position 460 (N460), a potential N-linked glycosylation site in the V5 region 806:913 Consistent with our previous observation, the resistant phenotype was associated with a single asparagine residue at position 460 (N460), a potential N-linked glycosylation site in the V5 region. 24369354 2 49 theme infected 321:328 arg1 patient 330:336 an HIV-1 infected patient 312:336 an HIV-1 infected patient during antiretroviral therapy 312:366 We have previously demonstrated the presence of VRC01-resistant strains in an HIV-1 infected patient during antiretroviral therapy. 24369354 5 50 gly glycosylation 879:891 arg2 site 893:896 a potential N-linked glycosylation site 858:896 a potential N-linked glycosylation site in the V5 region 858:913 Consistent with our previous observation, the resistant phenotype was associated with a single asparagine residue at position 460 (N460), a potential N-linked glycosylation site in the V5 region. 24369354 5 50 gly glycosylation 879:891 arg2 position 837:844 position 460 837:848 position 460 (N460) 837:855 Consistent with our previous observation, the resistant phenotype was associated with a single asparagine residue at position 460 (N460), a potential N-linked glycosylation site in the V5 region. 24369354 2 51 theme HIV-1 315:319 arg1 patient 330:336 an HIV-1 infected patient 312:336 an HIV-1 infected patient during antiretroviral therapy 312:366 We have previously demonstrated the presence of VRC01-resistant strains in an HIV-1 infected patient during antiretroviral therapy. 24369354 1 52 theme envelope 208:215 arg1 gp120 230:234 the envelope glycoprotein gp120 204:234 the envelope glycoprotein gp120 204:234 VRC01, a broadly neutralizing monoclonal antibody (bnmAb), can neutralize a diverse array of HIV-1 isolates by mimicking CD4 binding to the envelope glycoprotein gp120. 24369354 3 53 theme same 438:441 arg1 patient 443:449 the same patient 434:449 the same patient 434:449 Here, we report follow-up studies of two subsequent samples from the same patient. 24369354 5 54 theme potential 860:868 arg1 site 893:896 a potential N-linked glycosylation site 858:896 a potential N-linked glycosylation site in the V5 region 858:913 Consistent with our previous observation, the resistant phenotype was associated with a single asparagine residue at position 460 (N460), a potential N-linked glycosylation site in the V5 region. 24369354 5 54 theme potential 860:868 arg1 position 837:844 position 460 837:848 position 460 (N460) 837:855 Consistent with our previous observation, the resistant phenotype was associated with a single asparagine residue at position 460 (N460), a potential N-linked glycosylation site in the V5 region. 24369354 2 55 from presence 273:280 arg1 patient 330:336 an HIV-1 infected patient 312:336 an HIV-1 infected patient during antiretroviral therapy 312:366 We have previously demonstrated the presence of VRC01-resistant strains in an HIV-1 infected patient during antiretroviral therapy. 24369354 1 56 theme glycoprotein 217:228 arg1 gp120 230:234 the envelope glycoprotein gp120 204:234 the envelope glycoprotein gp120 204:234 VRC01, a broadly neutralizing monoclonal antibody (bnmAb), can neutralize a diverse array of HIV-1 isolates by mimicking CD4 binding to the envelope glycoprotein gp120. 24369354 3 57 from studies 395:401 arg1 patient 443:449 the same patient 434:449 the same patient 434:449 Here, we report follow-up studies of two subsequent samples from the same patient. 24369354 5 58 theme N-linked 870:877 arg1 site 893:896 a potential N-linked glycosylation site 858:896 a potential N-linked glycosylation site in the V5 region 858:913 Consistent with our previous observation, the resistant phenotype was associated with a single asparagine residue at position 460 (N460), a potential N-linked glycosylation site in the V5 region. 24369354 5 58 theme N-linked 870:877 arg1 position 837:844 position 460 837:848 position 460 (N460) 837:855 Consistent with our previous observation, the resistant phenotype was associated with a single asparagine residue at position 460 (N460), a potential N-linked glycosylation site in the V5 region. 24369354 5 59 theme single 808:813 arg1 residue 826:832 a single asparagine residue 806:832 a single asparagine residue at position 460 (N460), a potential N-linked glycosylation site in the V5 region 806:913 Consistent with our previous observation, the resistant phenotype was associated with a single asparagine residue at position 460 (N460), a potential N-linked glycosylation site in the V5 region. 25645918 4 0 theme broad 1005:1009 arg1 specificity 1021:1031 relative broad substrate specificity 996:1031 relative broad substrate specificity 996:1031 The timely expressed human azurophilic granule-resident β-hexosaminidase A displayed the capacity to generate paucimannosidic N-glycans by trimming hybrid/complex type N-glycan intermediates with relative broad substrate specificity. 25645918 9 1 from functions 1796:1804 arg1 neutrophils 1847:1857 activated human neutrophils 1831:1857 activated human neutrophils 1831:1857 Finally, paucimannosidic proteins displayed affinities to mannose-binding lectin, suggesting immune-related functions of paucimannosylation in activated human neutrophils. 25645918 0 2 from granules 78:85 arg1 proteins 52:59 bioactive paucimannosidic proteins 26:59 bioactive paucimannosidic proteins from azurophilic granules 26:85 Human neutrophils secrete bioactive paucimannosidic proteins from azurophilic granules into pathogen-infected sputum. 25645918 2 3 from advancements 310:321 arg1 characterization 351:366 system-wide biomolecular characterization 326:366 system-wide biomolecular characterization 326:366 Enabled by technology advancements in system-wide biomolecular characterization, we document that protein paucimannosylation is a significant host-derived molecular signature of neutrophil-rich sputum from pathogen-infected human lungs and is negligible in pathogen-free sputum. 25645918 3 4 theme N-glycans 597:605 arg1 types 572:576 Five types 567:576 Five types of paucimannosidic N-glycans 567:605 Five types of paucimannosidic N-glycans were carried by compartment-specific and inflammation-associated proteins of the azurophilic granules of human neutrophils including myeloperoxidase (MPO), azurocidin, and neutrophil elastase. 25645918 4 5 theme N-glycan 968:975 arg1 intermediates 977:989 hybrid/complex type N-glycan intermediates 948:989 hybrid/complex type N-glycan intermediates 948:989 The timely expressed human azurophilic granule-resident β-hexosaminidase A displayed the capacity to generate paucimannosidic N-glycans by trimming hybrid/complex type N-glycan intermediates with relative broad substrate specificity. 25645918 9 6 theme mannose-binding 1746:1760 arg1 lectin 1762:1767 mannose-binding lectin 1746:1767 mannose-binding lectin 1746:1767 Finally, paucimannosidic proteins displayed affinities to mannose-binding lectin, suggesting immune-related functions of paucimannosylation in activated human neutrophils. 25645918 3 7 theme compartment-specific 623:642 arg1 proteins 672:679 compartment-specific and inflammation-associated proteins 623:679 compartment-specific and inflammation-associated proteins of the azurophilic granules of human neutrophils including myeloperoxidase (MPO), azurocidin, and neutrophil elastase 623:797 Five types of paucimannosidic N-glycans were carried by compartment-specific and inflammation-associated proteins of the azurophilic granules of human neutrophils including myeloperoxidase (MPO), azurocidin, and neutrophil elastase. 25645918 3 7 theme compartment-specific 623:642 arg1 azurocidin 763:772 azurocidin 763:772 azurocidin 763:772 Five types of paucimannosidic N-glycans were carried by compartment-specific and inflammation-associated proteins of the azurophilic granules of human neutrophils including myeloperoxidase (MPO), azurocidin, and neutrophil elastase. 25645918 3 7 theme compartment-specific 623:642 arg1 myeloperoxidase 740:754 myeloperoxidase 740:754 myeloperoxidase (MPO) 740:760 Five types of paucimannosidic N-glycans were carried by compartment-specific and inflammation-associated proteins of the azurophilic granules of human neutrophils including myeloperoxidase (MPO), azurocidin, and neutrophil elastase. 25645918 3 7 theme compartment-specific 623:642 arg1 elastase 790:797 neutrophil elastase 779:797 neutrophil elastase 779:797 Five types of paucimannosidic N-glycans were carried by compartment-specific and inflammation-associated proteins of the azurophilic granules of human neutrophils including myeloperoxidase (MPO), azurocidin, and neutrophil elastase. 25645918 1 8 theme -linked 209:215 arg1 Asn 282:284 mannose(1-3)fucose(0-1)N-acetylglucosamine(2)Asn 237:284 mannose(1-3)fucose(0-1)N-acetylglucosamine(2)Asn 237:284 Unlike plants and invertebrates, mammals reportedly lack proteins displaying asparagine (N)-linked paucimannosylation (mannose(1-3)fucose(0-1)N-acetylglucosamine(2)Asn). 25645918 1 8 theme -linked 209:215 arg1 paucimannosylation 217:234 asparagine (N)-linked paucimannosylation 195:234 asparagine (N)-linked paucimannosylation (mannose(1-3)fucose(0-1)N-acetylglucosamine(2)Asn) 195:285 Unlike plants and invertebrates, mammals reportedly lack proteins displaying asparagine (N)-linked paucimannosylation (mannose(1-3)fucose(0-1)N-acetylglucosamine(2)Asn). 25645918 6 9 theme early 1382:1386 arg1 maturation 1399:1408 early neutrophil maturation 1382:1408 early neutrophil maturation 1382:1408 Furthermore, promyelocyte stage-specific expression of genes coding for paucimannosidic proteins and biosynthetic enzymes indicated a novel spatio-temporal biosynthetic route in early neutrophil maturation. 25645918 9 10 theme activated 1831:1839 arg1 neutrophils 1847:1857 activated human neutrophils 1831:1857 activated human neutrophils 1831:1857 Finally, paucimannosidic proteins displayed affinities to mannose-binding lectin, suggesting immune-related functions of paucimannosylation in activated human neutrophils. 25645918 2 11 from negligible 531:540 arg1 sputum 559:564 pathogen-free sputum 545:564 pathogen-free sputum 545:564 Enabled by technology advancements in system-wide biomolecular characterization, we document that protein paucimannosylation is a significant host-derived molecular signature of neutrophil-rich sputum from pathogen-infected human lungs and is negligible in pathogen-free sputum. 25645918 8 12 theme sputum 1585:1590 arg1 neutrophils 1592:1602 sputum neutrophils 1585:1602 sputum neutrophils 1585:1602 Paucimannosidic proteins from isolated and sputum neutrophils were preferentially secreted upon inoculation with virulent Pseudomonas aeruginosa. 25645918 3 13 theme inflammation-associated 648:670 arg1 proteins 672:679 compartment-specific and inflammation-associated proteins 623:679 compartment-specific and inflammation-associated proteins of the azurophilic granules of human neutrophils including myeloperoxidase (MPO), azurocidin, and neutrophil elastase 623:797 Five types of paucimannosidic N-glycans were carried by compartment-specific and inflammation-associated proteins of the azurophilic granules of human neutrophils including myeloperoxidase (MPO), azurocidin, and neutrophil elastase. 25645918 3 13 theme inflammation-associated 648:670 arg1 azurocidin 763:772 azurocidin 763:772 azurocidin 763:772 Five types of paucimannosidic N-glycans were carried by compartment-specific and inflammation-associated proteins of the azurophilic granules of human neutrophils including myeloperoxidase (MPO), azurocidin, and neutrophil elastase. 25645918 3 13 theme inflammation-associated 648:670 arg1 myeloperoxidase 740:754 myeloperoxidase 740:754 myeloperoxidase (MPO) 740:760 Five types of paucimannosidic N-glycans were carried by compartment-specific and inflammation-associated proteins of the azurophilic granules of human neutrophils including myeloperoxidase (MPO), azurocidin, and neutrophil elastase. 25645918 3 13 theme inflammation-associated 648:670 arg1 elastase 790:797 neutrophil elastase 779:797 neutrophil elastase 779:797 Five types of paucimannosidic N-glycans were carried by compartment-specific and inflammation-associated proteins of the azurophilic granules of human neutrophils including myeloperoxidase (MPO), azurocidin, and neutrophil elastase. 25645918 8 14 from isolated 1572:1579 arg1 proteins 1558:1565 Paucimannosidic proteins 1542:1565 Paucimannosidic proteins from isolated and sputum neutrophils 1542:1602 Paucimannosidic proteins from isolated and sputum neutrophils were preferentially secreted upon inoculation with virulent Pseudomonas aeruginosa. 25645918 5 15 theme β-hexosaminidase 1106:1121 arg1 A 1123:1123 β-hexosaminidase A 1106:1123 β-hexosaminidase A 1106:1123 Paucimannosidic N-glycoepitopes showed significant co-localization with β-hexosaminidase A and the azurophilic marker MPO in human neutrophils using immunocytochemistry. 25645918 6 16 theme promyelocyte 1217:1228 arg1 expression 1245:1254 promyelocyte stage-specific expression 1217:1254 promyelocyte stage-specific expression of genes coding for paucimannosidic proteins and biosynthetic enzymes 1217:1324 Furthermore, promyelocyte stage-specific expression of genes coding for paucimannosidic proteins and biosynthetic enzymes indicated a novel spatio-temporal biosynthetic route in early neutrophil maturation. 25645918 10 17 theme pathogen-based 2051:2064 arg1 inflammation 2066:2077 pathogen-based inflammation 2051:2077 pathogen-based inflammation 2051:2077 In conclusion, we are the first to document that human neutrophils produce, store and, upon activation, selectively secrete bioactive paucimannosidic proteins into sputum of lungs undergoing pathogen-based inflammation. 25645918 7 18 theme exogenous 1501:1509 arg1 origins 1511:1517 exogenous origins 1501:1517 exogenous origins of paucimannosylation 1501:1539 The absence of bacterial exoglycosidase activities and paucimannosidic N-glycans excluded exogenous origins of paucimannosylation. 25645918 3 19 theme azurophilic 688:698 arg1 granules 700:707 the azurophilic granules 684:707 the azurophilic granules of human neutrophils 684:728 Five types of paucimannosidic N-glycans were carried by compartment-specific and inflammation-associated proteins of the azurophilic granules of human neutrophils including myeloperoxidase (MPO), azurocidin, and neutrophil elastase. 25645918 5 20 theme Paucimannosidic 1034:1048 arg1 N-glycoepitopes 1050:1064 Paucimannosidic N-glycoepitopes 1034:1064 Paucimannosidic N-glycoepitopes 1034:1064 Paucimannosidic N-glycoepitopes showed significant co-localization with β-hexosaminidase A and the azurophilic marker MPO in human neutrophils using immunocytochemistry. 25645918 10 21 from conclusion 1863:1872 arg1 we 1875:1876 we 1875:1876 we 1875:1876 In conclusion, we are the first to document that human neutrophils produce, store and, upon activation, selectively secrete bioactive paucimannosidic proteins into sputum of lungs undergoing pathogen-based inflammation. 25645918 10 21 from conclusion 1863:1872 arg1 first 1886:1890 first 1886:1890 first 1886:1890 In conclusion, we are the first to document that human neutrophils produce, store and, upon activation, selectively secrete bioactive paucimannosidic proteins into sputum of lungs undergoing pathogen-based inflammation. 25645918 2 22 from signature 453:461 arg1 lungs 518:522 pathogen-infected human lungs 494:522 pathogen-infected human lungs 494:522 Enabled by technology advancements in system-wide biomolecular characterization, we document that protein paucimannosylation is a significant host-derived molecular signature of neutrophil-rich sputum from pathogen-infected human lungs and is negligible in pathogen-free sputum. 25645918 0 23 theme pathogen-infected 92:108 arg1 sputum 110:115 pathogen-infected sputum 92:115 pathogen-infected sputum 92:115 Human neutrophils secrete bioactive paucimannosidic proteins from azurophilic granules into pathogen-infected sputum. 25645918 7 24 theme exoglycosidase 1436:1449 arg1 activities 1451:1460 bacterial exoglycosidase activities 1426:1460 bacterial exoglycosidase activities 1426:1460 The absence of bacterial exoglycosidase activities and paucimannosidic N-glycans excluded exogenous origins of paucimannosylation. 25645918 5 25 theme human 1159:1163 arg1 neutrophils 1165:1175 human neutrophils 1159:1175 human neutrophils using immunocytochemistry 1159:1201 Paucimannosidic N-glycoepitopes showed significant co-localization with β-hexosaminidase A and the azurophilic marker MPO in human neutrophils using immunocytochemistry. 25645918 2 26 theme sputum 482:487 arg1 paucimannosylation 394:411 protein paucimannosylation 386:411 protein paucimannosylation 386:411 Enabled by technology advancements in system-wide biomolecular characterization, we document that protein paucimannosylation is a significant host-derived molecular signature of neutrophil-rich sputum from pathogen-infected human lungs and is negligible in pathogen-free sputum. 25645918 2 26 theme sputum 482:487 arg1 signature 453:461 a significant host-derived molecular signature 416:461 a significant host-derived molecular signature of neutrophil-rich sputum from pathogen-infected human lungs 416:522 Enabled by technology advancements in system-wide biomolecular characterization, we document that protein paucimannosylation is a significant host-derived molecular signature of neutrophil-rich sputum from pathogen-infected human lungs and is negligible in pathogen-free sputum. 25645918 4 27 theme human 821:825 arg1 A 873:873 The timely expressed human azurophilic granule-resident β-hexosaminidase A 800:873 The timely expressed human azurophilic granule-resident β-hexosaminidase A 800:873 The timely expressed human azurophilic granule-resident β-hexosaminidase A displayed the capacity to generate paucimannosidic N-glycans by trimming hybrid/complex type N-glycan intermediates with relative broad substrate specificity. 25645918 2 28 theme protein 386:392 arg1 paucimannosylation 394:411 protein paucimannosylation 386:411 protein paucimannosylation 386:411 Enabled by technology advancements in system-wide biomolecular characterization, we document that protein paucimannosylation is a significant host-derived molecular signature of neutrophil-rich sputum from pathogen-infected human lungs and is negligible in pathogen-free sputum. 25645918 2 28 theme protein 386:392 arg1 signature 453:461 a significant host-derived molecular signature 416:461 a significant host-derived molecular signature of neutrophil-rich sputum from pathogen-infected human lungs 416:522 Enabled by technology advancements in system-wide biomolecular characterization, we document that protein paucimannosylation is a significant host-derived molecular signature of neutrophil-rich sputum from pathogen-infected human lungs and is negligible in pathogen-free sputum. 25645918 0 29 theme Human 0:4 arg1 neutrophils 6:16 Human neutrophils 0:16 Human neutrophils 0:16 Human neutrophils secrete bioactive paucimannosidic proteins from azurophilic granules into pathogen-infected sputum. 25645918 4 30 theme granule-resident 839:854 arg1 A 873:873 The timely expressed human azurophilic granule-resident β-hexosaminidase A 800:873 The timely expressed human azurophilic granule-resident β-hexosaminidase A 800:873 The timely expressed human azurophilic granule-resident β-hexosaminidase A displayed the capacity to generate paucimannosidic N-glycans by trimming hybrid/complex type N-glycan intermediates with relative broad substrate specificity. 25645918 2 31 theme molecular 443:451 arg1 paucimannosylation 394:411 protein paucimannosylation 386:411 protein paucimannosylation 386:411 Enabled by technology advancements in system-wide biomolecular characterization, we document that protein paucimannosylation is a significant host-derived molecular signature of neutrophil-rich sputum from pathogen-infected human lungs and is negligible in pathogen-free sputum. 25645918 2 31 theme molecular 443:451 arg1 signature 453:461 a significant host-derived molecular signature 416:461 a significant host-derived molecular signature of neutrophil-rich sputum from pathogen-infected human lungs 416:522 Enabled by technology advancements in system-wide biomolecular characterization, we document that protein paucimannosylation is a significant host-derived molecular signature of neutrophil-rich sputum from pathogen-infected human lungs and is negligible in pathogen-free sputum. 25645918 5 32 theme azurophilic 1133:1143 arg1 MPO 1152:1154 the azurophilic marker MPO 1129:1154 the azurophilic marker MPO in human neutrophils using immunocytochemistry 1129:1201 Paucimannosidic N-glycoepitopes showed significant co-localization with β-hexosaminidase A and the azurophilic marker MPO in human neutrophils using immunocytochemistry. 25645918 6 33 theme genes 1259:1263 arg1 expression 1245:1254 promyelocyte stage-specific expression 1217:1254 promyelocyte stage-specific expression of genes coding for paucimannosidic proteins and biosynthetic enzymes 1217:1324 Furthermore, promyelocyte stage-specific expression of genes coding for paucimannosidic proteins and biosynthetic enzymes indicated a novel spatio-temporal biosynthetic route in early neutrophil maturation. 25645918 10 34 theme lungs 2034:2038 arg1 sputum 2024:2029 sputum 2024:2029 sputum of lungs undergoing pathogen-based inflammation 2024:2077 In conclusion, we are the first to document that human neutrophils produce, store and, upon activation, selectively secrete bioactive paucimannosidic proteins into sputum of lungs undergoing pathogen-based inflammation. 25645918 2 35 theme significant 418:428 arg1 paucimannosylation 394:411 protein paucimannosylation 386:411 protein paucimannosylation 386:411 Enabled by technology advancements in system-wide biomolecular characterization, we document that protein paucimannosylation is a significant host-derived molecular signature of neutrophil-rich sputum from pathogen-infected human lungs and is negligible in pathogen-free sputum. 25645918 2 35 theme significant 418:428 arg1 signature 453:461 a significant host-derived molecular signature 416:461 a significant host-derived molecular signature of neutrophil-rich sputum from pathogen-infected human lungs 416:522 Enabled by technology advancements in system-wide biomolecular characterization, we document that protein paucimannosylation is a significant host-derived molecular signature of neutrophil-rich sputum from pathogen-infected human lungs and is negligible in pathogen-free sputum. 25645918 0 36 theme paucimannosidic 36:50 arg1 proteins 52:59 bioactive paucimannosidic proteins 26:59 bioactive paucimannosidic proteins from azurophilic granules 26:85 Human neutrophils secrete bioactive paucimannosidic proteins from azurophilic granules into pathogen-infected sputum. 25645918 2 37 theme pathogen-infected 494:510 arg1 lungs 518:522 pathogen-infected human lungs 494:522 pathogen-infected human lungs 494:522 Enabled by technology advancements in system-wide biomolecular characterization, we document that protein paucimannosylation is a significant host-derived molecular signature of neutrophil-rich sputum from pathogen-infected human lungs and is negligible in pathogen-free sputum. 25645918 3 38 theme neutrophils 718:728 arg1 granules 700:707 the azurophilic granules 684:707 the azurophilic granules of human neutrophils 684:728 Five types of paucimannosidic N-glycans were carried by compartment-specific and inflammation-associated proteins of the azurophilic granules of human neutrophils including myeloperoxidase (MPO), azurocidin, and neutrophil elastase. 25645918 4 39 theme hybrid/complex 948:961 arg1 intermediates 977:989 hybrid/complex type N-glycan intermediates 948:989 hybrid/complex type N-glycan intermediates 948:989 The timely expressed human azurophilic granule-resident β-hexosaminidase A displayed the capacity to generate paucimannosidic N-glycans by trimming hybrid/complex type N-glycan intermediates with relative broad substrate specificity. 25645918 2 40 theme biomolecular 338:349 arg1 characterization 351:366 system-wide biomolecular characterization 326:366 system-wide biomolecular characterization 326:366 Enabled by technology advancements in system-wide biomolecular characterization, we document that protein paucimannosylation is a significant host-derived molecular signature of neutrophil-rich sputum from pathogen-infected human lungs and is negligible in pathogen-free sputum. 25645918 6 41 theme biosynthetic 1360:1371 arg1 route 1373:1377 a novel spatio-temporal biosynthetic route 1336:1377 a novel spatio-temporal biosynthetic route in early neutrophil maturation 1336:1408 Furthermore, promyelocyte stage-specific expression of genes coding for paucimannosidic proteins and biosynthetic enzymes indicated a novel spatio-temporal biosynthetic route in early neutrophil maturation. 25645918 6 42 theme novel 1338:1342 arg1 route 1373:1377 a novel spatio-temporal biosynthetic route 1336:1377 a novel spatio-temporal biosynthetic route in early neutrophil maturation 1336:1408 Furthermore, promyelocyte stage-specific expression of genes coding for paucimannosidic proteins and biosynthetic enzymes indicated a novel spatio-temporal biosynthetic route in early neutrophil maturation. 25645918 10 43 theme human 1909:1913 arg1 neutrophils 1915:1925 human neutrophils 1909:1925 human neutrophils 1909:1925 In conclusion, we are the first to document that human neutrophils produce, store and, upon activation, selectively secrete bioactive paucimannosidic proteins into sputum of lungs undergoing pathogen-based inflammation. 25645918 2 44 link host-derived 430:441 arg1 paucimannosylation 394:411 protein paucimannosylation 386:411 protein paucimannosylation 386:411 Enabled by technology advancements in system-wide biomolecular characterization, we document that protein paucimannosylation is a significant host-derived molecular signature of neutrophil-rich sputum from pathogen-infected human lungs and is negligible in pathogen-free sputum. 25645918 2 44 link host-derived 430:441 arg1 signature 453:461 a significant host-derived molecular signature 416:461 a significant host-derived molecular signature of neutrophil-rich sputum from pathogen-infected human lungs 416:522 Enabled by technology advancements in system-wide biomolecular characterization, we document that protein paucimannosylation is a significant host-derived molecular signature of neutrophil-rich sputum from pathogen-infected human lungs and is negligible in pathogen-free sputum. 25645918 4 45 theme paucimannosidic 910:924 arg1 N-glycans 926:934 paucimannosidic N-glycans 910:934 paucimannosidic N-glycans 910:934 The timely expressed human azurophilic granule-resident β-hexosaminidase A displayed the capacity to generate paucimannosidic N-glycans by trimming hybrid/complex type N-glycan intermediates with relative broad substrate specificity. 25645918 1 46 theme fucose 249:254 arg1 Asn 282:284 mannose(1-3)fucose(0-1)N-acetylglucosamine(2)Asn 237:284 mannose(1-3)fucose(0-1)N-acetylglucosamine(2)Asn 237:284 Unlike plants and invertebrates, mammals reportedly lack proteins displaying asparagine (N)-linked paucimannosylation (mannose(1-3)fucose(0-1)N-acetylglucosamine(2)Asn). 25645918 1 46 theme fucose 249:254 arg1 paucimannosylation 217:234 asparagine (N)-linked paucimannosylation 195:234 asparagine (N)-linked paucimannosylation (mannose(1-3)fucose(0-1)N-acetylglucosamine(2)Asn) 195:285 Unlike plants and invertebrates, mammals reportedly lack proteins displaying asparagine (N)-linked paucimannosylation (mannose(1-3)fucose(0-1)N-acetylglucosamine(2)Asn). 25645918 3 47 theme neutrophil 779:788 arg1 elastase 790:797 neutrophil elastase 779:797 neutrophil elastase 779:797 Five types of paucimannosidic N-glycans were carried by compartment-specific and inflammation-associated proteins of the azurophilic granules of human neutrophils including myeloperoxidase (MPO), azurocidin, and neutrophil elastase. 25645918 1 48 theme 0-1 256:258 arg1 Asn 282:284 mannose(1-3)fucose(0-1)N-acetylglucosamine(2)Asn 237:284 mannose(1-3)fucose(0-1)N-acetylglucosamine(2)Asn 237:284 Unlike plants and invertebrates, mammals reportedly lack proteins displaying asparagine (N)-linked paucimannosylation (mannose(1-3)fucose(0-1)N-acetylglucosamine(2)Asn). 25645918 1 48 theme 0-1 256:258 arg1 paucimannosylation 217:234 asparagine (N)-linked paucimannosylation 195:234 asparagine (N)-linked paucimannosylation (mannose(1-3)fucose(0-1)N-acetylglucosamine(2)Asn) 195:285 Unlike plants and invertebrates, mammals reportedly lack proteins displaying asparagine (N)-linked paucimannosylation (mannose(1-3)fucose(0-1)N-acetylglucosamine(2)Asn). 25645918 4 49 theme relative 996:1003 arg1 specificity 1021:1031 relative broad substrate specificity 996:1031 relative broad substrate specificity 996:1031 The timely expressed human azurophilic granule-resident β-hexosaminidase A displayed the capacity to generate paucimannosidic N-glycans by trimming hybrid/complex type N-glycan intermediates with relative broad substrate specificity. 25645918 6 50 theme biosynthetic 1305:1316 arg1 enzymes 1318:1324 biosynthetic enzymes 1305:1324 biosynthetic enzymes 1305:1324 Furthermore, promyelocyte stage-specific expression of genes coding for paucimannosidic proteins and biosynthetic enzymes indicated a novel spatio-temporal biosynthetic route in early neutrophil maturation. 25645918 3 51 theme paucimannosidic 581:595 arg1 N-glycans 597:605 paucimannosidic N-glycans 581:605 paucimannosidic N-glycans 581:605 Five types of paucimannosidic N-glycans were carried by compartment-specific and inflammation-associated proteins of the azurophilic granules of human neutrophils including myeloperoxidase (MPO), azurocidin, and neutrophil elastase. 25645918 5 52 from MPO 1152:1154 arg1 neutrophils 1165:1175 human neutrophils 1159:1175 human neutrophils using immunocytochemistry 1159:1201 Paucimannosidic N-glycoepitopes showed significant co-localization with β-hexosaminidase A and the azurophilic marker MPO in human neutrophils using immunocytochemistry. 25645918 1 53 theme N-acetylglucosamine 260:278 arg1 Asn 282:284 mannose(1-3)fucose(0-1)N-acetylglucosamine(2)Asn 237:284 mannose(1-3)fucose(0-1)N-acetylglucosamine(2)Asn 237:284 Unlike plants and invertebrates, mammals reportedly lack proteins displaying asparagine (N)-linked paucimannosylation (mannose(1-3)fucose(0-1)N-acetylglucosamine(2)Asn). 25645918 1 53 theme N-acetylglucosamine 260:278 arg1 paucimannosylation 217:234 asparagine (N)-linked paucimannosylation 195:234 asparagine (N)-linked paucimannosylation (mannose(1-3)fucose(0-1)N-acetylglucosamine(2)Asn) 195:285 Unlike plants and invertebrates, mammals reportedly lack proteins displaying asparagine (N)-linked paucimannosylation (mannose(1-3)fucose(0-1)N-acetylglucosamine(2)Asn). 25645918 4 54 theme substrate 1011:1019 arg1 specificity 1021:1031 relative broad substrate specificity 996:1031 relative broad substrate specificity 996:1031 The timely expressed human azurophilic granule-resident β-hexosaminidase A displayed the capacity to generate paucimannosidic N-glycans by trimming hybrid/complex type N-glycan intermediates with relative broad substrate specificity. 25645918 9 55 theme immune-related 1781:1794 arg1 functions 1796:1804 immune-related functions 1781:1804 immune-related functions of paucimannosylation in activated human neutrophils 1781:1857 Finally, paucimannosidic proteins displayed affinities to mannose-binding lectin, suggesting immune-related functions of paucimannosylation in activated human neutrophils. 25645918 4 56 theme type 963:966 arg1 intermediates 977:989 hybrid/complex type N-glycan intermediates 948:989 hybrid/complex type N-glycan intermediates 948:989 The timely expressed human azurophilic granule-resident β-hexosaminidase A displayed the capacity to generate paucimannosidic N-glycans by trimming hybrid/complex type N-glycan intermediates with relative broad substrate specificity. 25645918 7 57 theme N-glycans 1482:1490 arg1 absence 1415:1421 The absence 1411:1421 The absence of bacterial exoglycosidase activities and paucimannosidic N-glycans 1411:1490 The absence of bacterial exoglycosidase activities and paucimannosidic N-glycans excluded exogenous origins of paucimannosylation. 25645918 2 58 theme technology 299:308 arg1 advancements 310:321 technology advancements 299:321 technology advancements in system-wide biomolecular characterization 299:366 Enabled by technology advancements in system-wide biomolecular characterization, we document that protein paucimannosylation is a significant host-derived molecular signature of neutrophil-rich sputum from pathogen-infected human lungs and is negligible in pathogen-free sputum. 25645918 6 59 theme neutrophil 1388:1397 arg1 maturation 1399:1408 early neutrophil maturation 1382:1408 early neutrophil maturation 1382:1408 Furthermore, promyelocyte stage-specific expression of genes coding for paucimannosidic proteins and biosynthetic enzymes indicated a novel spatio-temporal biosynthetic route in early neutrophil maturation. 25645918 8 60 theme Paucimannosidic 1542:1556 arg1 proteins 1558:1565 Paucimannosidic proteins 1542:1565 Paucimannosidic proteins from isolated and sputum neutrophils 1542:1602 Paucimannosidic proteins from isolated and sputum neutrophils were preferentially secreted upon inoculation with virulent Pseudomonas aeruginosa. 25645918 10 61 theme bioactive 1984:1992 arg1 proteins 2010:2017 bioactive paucimannosidic proteins 1984:2017 bioactive paucimannosidic proteins 1984:2017 In conclusion, we are the first to document that human neutrophils produce, store and, upon activation, selectively secrete bioactive paucimannosidic proteins into sputum of lungs undergoing pathogen-based inflammation. 25645918 9 62 theme paucimannosylation 1809:1826 arg1 functions 1796:1804 immune-related functions 1781:1804 immune-related functions of paucimannosylation in activated human neutrophils 1781:1857 Finally, paucimannosidic proteins displayed affinities to mannose-binding lectin, suggesting immune-related functions of paucimannosylation in activated human neutrophils. 25645918 1 63 theme mannose 237:243 arg1 Asn 282:284 mannose(1-3)fucose(0-1)N-acetylglucosamine(2)Asn 237:284 mannose(1-3)fucose(0-1)N-acetylglucosamine(2)Asn 237:284 Unlike plants and invertebrates, mammals reportedly lack proteins displaying asparagine (N)-linked paucimannosylation (mannose(1-3)fucose(0-1)N-acetylglucosamine(2)Asn). 25645918 1 63 theme mannose 237:243 arg1 paucimannosylation 217:234 asparagine (N)-linked paucimannosylation 195:234 asparagine (N)-linked paucimannosylation (mannose(1-3)fucose(0-1)N-acetylglucosamine(2)Asn) 195:285 Unlike plants and invertebrates, mammals reportedly lack proteins displaying asparagine (N)-linked paucimannosylation (mannose(1-3)fucose(0-1)N-acetylglucosamine(2)Asn). 25645918 5 64 theme significant 1073:1083 arg1 co-localization 1085:1099 significant co-localization 1073:1099 significant co-localization with β-hexosaminidase A and the azurophilic marker MPO in human neutrophils using immunocytochemistry 1073:1201 Paucimannosidic N-glycoepitopes showed significant co-localization with β-hexosaminidase A and the azurophilic marker MPO in human neutrophils using immunocytochemistry. 25645918 2 65 from sputum 559:564 arg1 negligible 531:540 negligible 531:540 negligible 531:540 Enabled by technology advancements in system-wide biomolecular characterization, we document that protein paucimannosylation is a significant host-derived molecular signature of neutrophil-rich sputum from pathogen-infected human lungs and is negligible in pathogen-free sputum. 25645918 3 66 theme granules 700:707 arg1 proteins 672:679 compartment-specific and inflammation-associated proteins 623:679 compartment-specific and inflammation-associated proteins of the azurophilic granules of human neutrophils including myeloperoxidase (MPO), azurocidin, and neutrophil elastase 623:797 Five types of paucimannosidic N-glycans were carried by compartment-specific and inflammation-associated proteins of the azurophilic granules of human neutrophils including myeloperoxidase (MPO), azurocidin, and neutrophil elastase. 25645918 3 66 theme granules 700:707 arg1 azurocidin 763:772 azurocidin 763:772 azurocidin 763:772 Five types of paucimannosidic N-glycans were carried by compartment-specific and inflammation-associated proteins of the azurophilic granules of human neutrophils including myeloperoxidase (MPO), azurocidin, and neutrophil elastase. 25645918 3 66 theme granules 700:707 arg1 myeloperoxidase 740:754 myeloperoxidase 740:754 myeloperoxidase (MPO) 740:760 Five types of paucimannosidic N-glycans were carried by compartment-specific and inflammation-associated proteins of the azurophilic granules of human neutrophils including myeloperoxidase (MPO), azurocidin, and neutrophil elastase. 25645918 3 66 theme granules 700:707 arg1 elastase 790:797 neutrophil elastase 779:797 neutrophil elastase 779:797 Five types of paucimannosidic N-glycans were carried by compartment-specific and inflammation-associated proteins of the azurophilic granules of human neutrophils including myeloperoxidase (MPO), azurocidin, and neutrophil elastase. 25645918 6 67 theme stage-specific 1230:1243 arg1 expression 1245:1254 promyelocyte stage-specific expression 1217:1254 promyelocyte stage-specific expression of genes coding for paucimannosidic proteins and biosynthetic enzymes 1217:1324 Furthermore, promyelocyte stage-specific expression of genes coding for paucimannosidic proteins and biosynthetic enzymes indicated a novel spatio-temporal biosynthetic route in early neutrophil maturation. 25645918 1 68 dep Asn 282:284 arg1 2 280:280 2 280:280 2 280:280 Unlike plants and invertebrates, mammals reportedly lack proteins displaying asparagine (N)-linked paucimannosylation (mannose(1-3)fucose(0-1)N-acetylglucosamine(2)Asn). 25645918 7 69 theme paucimannosidic 1466:1480 arg1 N-glycans 1482:1490 paucimannosidic N-glycans 1466:1490 paucimannosidic N-glycans 1466:1490 The absence of bacterial exoglycosidase activities and paucimannosidic N-glycans excluded exogenous origins of paucimannosylation. 25645918 7 70 theme activities 1451:1460 arg1 absence 1415:1421 The absence 1411:1421 The absence of bacterial exoglycosidase activities and paucimannosidic N-glycans 1411:1490 The absence of bacterial exoglycosidase activities and paucimannosidic N-glycans excluded exogenous origins of paucimannosylation. 25645918 8 71 from neutrophils 1592:1602 arg1 proteins 1558:1565 Paucimannosidic proteins 1542:1565 Paucimannosidic proteins from isolated and sputum neutrophils 1542:1602 Paucimannosidic proteins from isolated and sputum neutrophils were preferentially secreted upon inoculation with virulent Pseudomonas aeruginosa. 25645918 5 72 theme marker 1145:1150 arg1 MPO 1152:1154 the azurophilic marker MPO 1129:1154 the azurophilic marker MPO in human neutrophils using immunocytochemistry 1129:1201 Paucimannosidic N-glycoepitopes showed significant co-localization with β-hexosaminidase A and the azurophilic marker MPO in human neutrophils using immunocytochemistry. 25645918 10 73 from first 1886:1890 arg1 conclusion 1863:1872 conclusion 1863:1872 conclusion 1863:1872 In conclusion, we are the first to document that human neutrophils produce, store and, upon activation, selectively secrete bioactive paucimannosidic proteins into sputum of lungs undergoing pathogen-based inflammation. 25645918 4 74 theme β-hexosaminidase 856:871 arg1 A 873:873 The timely expressed human azurophilic granule-resident β-hexosaminidase A 800:873 The timely expressed human azurophilic granule-resident β-hexosaminidase A 800:873 The timely expressed human azurophilic granule-resident β-hexosaminidase A displayed the capacity to generate paucimannosidic N-glycans by trimming hybrid/complex type N-glycan intermediates with relative broad substrate specificity. 25645918 7 75 theme bacterial 1426:1434 arg1 activities 1451:1460 bacterial exoglycosidase activities 1426:1460 bacterial exoglycosidase activities 1426:1460 The absence of bacterial exoglycosidase activities and paucimannosidic N-glycans excluded exogenous origins of paucimannosylation. 25645918 2 76 theme pathogen-free 545:557 arg1 sputum 559:564 pathogen-free sputum 545:564 pathogen-free sputum 545:564 Enabled by technology advancements in system-wide biomolecular characterization, we document that protein paucimannosylation is a significant host-derived molecular signature of neutrophil-rich sputum from pathogen-infected human lungs and is negligible in pathogen-free sputum. 25645918 2 77 from lungs 518:522 arg1 paucimannosylation 394:411 protein paucimannosylation 386:411 protein paucimannosylation 386:411 Enabled by technology advancements in system-wide biomolecular characterization, we document that protein paucimannosylation is a significant host-derived molecular signature of neutrophil-rich sputum from pathogen-infected human lungs and is negligible in pathogen-free sputum. 25645918 2 77 from lungs 518:522 arg1 signature 453:461 a significant host-derived molecular signature 416:461 a significant host-derived molecular signature of neutrophil-rich sputum from pathogen-infected human lungs 416:522 Enabled by technology advancements in system-wide biomolecular characterization, we document that protein paucimannosylation is a significant host-derived molecular signature of neutrophil-rich sputum from pathogen-infected human lungs and is negligible in pathogen-free sputum. 25645918 2 77 from lungs 518:522 arg1 sputum 482:487 neutrophil-rich sputum 466:487 neutrophil-rich sputum from pathogen-infected human lungs 466:522 Enabled by technology advancements in system-wide biomolecular characterization, we document that protein paucimannosylation is a significant host-derived molecular signature of neutrophil-rich sputum from pathogen-infected human lungs and is negligible in pathogen-free sputum. 25645918 1 78 link -linked 209:215 arg1 Asn 282:284 mannose(1-3)fucose(0-1)N-acetylglucosamine(2)Asn 237:284 mannose(1-3)fucose(0-1)N-acetylglucosamine(2)Asn 237:284 Unlike plants and invertebrates, mammals reportedly lack proteins displaying asparagine (N)-linked paucimannosylation (mannose(1-3)fucose(0-1)N-acetylglucosamine(2)Asn). 25645918 1 78 link -linked 209:215 arg1 paucimannosylation 217:234 asparagine (N)-linked paucimannosylation 195:234 asparagine (N)-linked paucimannosylation (mannose(1-3)fucose(0-1)N-acetylglucosamine(2)Asn) 195:285 Unlike plants and invertebrates, mammals reportedly lack proteins displaying asparagine (N)-linked paucimannosylation (mannose(1-3)fucose(0-1)N-acetylglucosamine(2)Asn). 25645918 6 79 theme paucimannosidic 1276:1290 arg1 proteins 1292:1299 paucimannosidic proteins 1276:1299 paucimannosidic proteins 1276:1299 Furthermore, promyelocyte stage-specific expression of genes coding for paucimannosidic proteins and biosynthetic enzymes indicated a novel spatio-temporal biosynthetic route in early neutrophil maturation. 25645918 2 80 theme neutrophil-rich 466:480 arg1 sputum 482:487 neutrophil-rich sputum 466:487 neutrophil-rich sputum from pathogen-infected human lungs 466:522 Enabled by technology advancements in system-wide biomolecular characterization, we document that protein paucimannosylation is a significant host-derived molecular signature of neutrophil-rich sputum from pathogen-infected human lungs and is negligible in pathogen-free sputum. 25645918 5 81 with co-localization 1085:1099 arg1 MPO 1152:1154 the azurophilic marker MPO 1129:1154 the azurophilic marker MPO in human neutrophils using immunocytochemistry 1129:1201 Paucimannosidic N-glycoepitopes showed significant co-localization with β-hexosaminidase A and the azurophilic marker MPO in human neutrophils using immunocytochemistry. 25645918 5 81 with co-localization 1085:1099 arg1 A 1123:1123 β-hexosaminidase A 1106:1123 β-hexosaminidase A 1106:1123 Paucimannosidic N-glycoepitopes showed significant co-localization with β-hexosaminidase A and the azurophilic marker MPO in human neutrophils using immunocytochemistry. 25645918 4 82 theme expressed 811:819 arg1 A 873:873 The timely expressed human azurophilic granule-resident β-hexosaminidase A 800:873 The timely expressed human azurophilic granule-resident β-hexosaminidase A 800:873 The timely expressed human azurophilic granule-resident β-hexosaminidase A displayed the capacity to generate paucimannosidic N-glycans by trimming hybrid/complex type N-glycan intermediates with relative broad substrate specificity. 25645918 10 83 theme paucimannosidic 1994:2008 arg1 proteins 2010:2017 bioactive paucimannosidic proteins 1984:2017 bioactive paucimannosidic proteins 1984:2017 In conclusion, we are the first to document that human neutrophils produce, store and, upon activation, selectively secrete bioactive paucimannosidic proteins into sputum of lungs undergoing pathogen-based inflammation. 25645918 0 84 theme bioactive 26:34 arg1 proteins 52:59 bioactive paucimannosidic proteins 26:59 bioactive paucimannosidic proteins from azurophilic granules 26:85 Human neutrophils secrete bioactive paucimannosidic proteins from azurophilic granules into pathogen-infected sputum. 25645918 4 85 theme azurophilic 827:837 arg1 A 873:873 The timely expressed human azurophilic granule-resident β-hexosaminidase A 800:873 The timely expressed human azurophilic granule-resident β-hexosaminidase A 800:873 The timely expressed human azurophilic granule-resident β-hexosaminidase A displayed the capacity to generate paucimannosidic N-glycans by trimming hybrid/complex type N-glycan intermediates with relative broad substrate specificity. 25645918 2 86 theme host-derived 430:441 arg1 paucimannosylation 394:411 protein paucimannosylation 386:411 protein paucimannosylation 386:411 Enabled by technology advancements in system-wide biomolecular characterization, we document that protein paucimannosylation is a significant host-derived molecular signature of neutrophil-rich sputum from pathogen-infected human lungs and is negligible in pathogen-free sputum. 25645918 2 86 theme host-derived 430:441 arg1 signature 453:461 a significant host-derived molecular signature 416:461 a significant host-derived molecular signature of neutrophil-rich sputum from pathogen-infected human lungs 416:522 Enabled by technology advancements in system-wide biomolecular characterization, we document that protein paucimannosylation is a significant host-derived molecular signature of neutrophil-rich sputum from pathogen-infected human lungs and is negligible in pathogen-free sputum. 25645918 9 87 theme human 1841:1845 arg1 neutrophils 1847:1857 activated human neutrophils 1831:1857 activated human neutrophils 1831:1857 Finally, paucimannosidic proteins displayed affinities to mannose-binding lectin, suggesting immune-related functions of paucimannosylation in activated human neutrophils. 25645918 2 88 theme human 512:516 arg1 lungs 518:522 pathogen-infected human lungs 494:522 pathogen-infected human lungs 494:522 Enabled by technology advancements in system-wide biomolecular characterization, we document that protein paucimannosylation is a significant host-derived molecular signature of neutrophil-rich sputum from pathogen-infected human lungs and is negligible in pathogen-free sputum. 25645918 3 89 theme human 712:716 arg1 neutrophils 718:728 human neutrophils 712:728 human neutrophils 712:728 Five types of paucimannosidic N-glycans were carried by compartment-specific and inflammation-associated proteins of the azurophilic granules of human neutrophils including myeloperoxidase (MPO), azurocidin, and neutrophil elastase. 25645918 0 90 theme azurophilic 66:76 arg1 granules 78:85 azurophilic granules 66:85 azurophilic granules 66:85 Human neutrophils secrete bioactive paucimannosidic proteins from azurophilic granules into pathogen-infected sputum. 25645918 8 91 with inoculation 1638:1648 arg1 aeruginosa 1676:1685 virulent Pseudomonas aeruginosa 1655:1685 virulent Pseudomonas aeruginosa 1655:1685 Paucimannosidic proteins from isolated and sputum neutrophils were preferentially secreted upon inoculation with virulent Pseudomonas aeruginosa. 25645918 6 92 from route 1373:1377 arg1 maturation 1399:1408 early neutrophil maturation 1382:1408 early neutrophil maturation 1382:1408 Furthermore, promyelocyte stage-specific expression of genes coding for paucimannosidic proteins and biosynthetic enzymes indicated a novel spatio-temporal biosynthetic route in early neutrophil maturation. 25645918 2 93 theme system-wide 326:336 arg1 characterization 351:366 system-wide biomolecular characterization 326:366 system-wide biomolecular characterization 326:366 Enabled by technology advancements in system-wide biomolecular characterization, we document that protein paucimannosylation is a significant host-derived molecular signature of neutrophil-rich sputum from pathogen-infected human lungs and is negligible in pathogen-free sputum. 25645918 9 94 theme paucimannosidic 1697:1711 arg1 proteins 1713:1720 paucimannosidic proteins 1697:1720 paucimannosidic proteins 1697:1720 Finally, paucimannosidic proteins displayed affinities to mannose-binding lectin, suggesting immune-related functions of paucimannosylation in activated human neutrophils. 25645918 6 95 theme spatio-temporal 1344:1358 arg1 route 1373:1377 a novel spatio-temporal biosynthetic route 1336:1377 a novel spatio-temporal biosynthetic route in early neutrophil maturation 1336:1408 Furthermore, promyelocyte stage-specific expression of genes coding for paucimannosidic proteins and biosynthetic enzymes indicated a novel spatio-temporal biosynthetic route in early neutrophil maturation. 25645918 5 96 from A 1123:1123 arg1 neutrophils 1165:1175 human neutrophils 1159:1175 human neutrophils using immunocytochemistry 1159:1201 Paucimannosidic N-glycoepitopes showed significant co-localization with β-hexosaminidase A and the azurophilic marker MPO in human neutrophils using immunocytochemistry. 25645918 7 97 theme paucimannosylation 1522:1539 arg1 origins 1511:1517 exogenous origins 1501:1517 exogenous origins of paucimannosylation 1501:1539 The absence of bacterial exoglycosidase activities and paucimannosidic N-glycans excluded exogenous origins of paucimannosylation. 24971706 4 0 theme Ca 641:642 arg1 mobilisation 648:659 NTZ-mediated Ca(2+) mobilisation 628:659 NTZ-mediated Ca(2+) mobilisation 628:659 In addition to PKR and eIF2α phosphorylation, consequences of NTZ-mediated Ca(2+) mobilisation included induction of chronic sub-lethal ER stress as well as perturbation of viral protein N-linked glycosylation and trafficking. 24971706 1 1 theme Japanese 130:137 arg1 encephalitis 139:150 Japanese encephalitis 130:150 Japanese encephalitis 130:150 Nitazoxanide (NTZ) inhibits influenza, Japanese encephalitis, hepatitis B and hepatitis C virus replication but effects on the replication of other members of the Flaviviridae family has yet to be defined. 24971706 5 2 theme -binding 880:887 arg1 proteins 889:896 Ca(2+)-binding proteins 874:896 Ca(2+)-binding proteins 874:896 To adapt to NTZ-mediated ER stress, NTZ treated cells upregulated translation of Ca(2+)-binding proteins, including the ER chaperone Bip and the cytosolic pro-survival and anti-viral protein TCTP. 24971706 5 2 theme -binding 880:887 arg1 TCTP 984:987 the cytosolic pro-survival and anti-viral protein TCTP 934:987 the cytosolic pro-survival and anti-viral protein TCTP 934:987 To adapt to NTZ-mediated ER stress, NTZ treated cells upregulated translation of Ca(2+)-binding proteins, including the ER chaperone Bip and the cytosolic pro-survival and anti-viral protein TCTP. 24971706 5 2 theme -binding 880:887 arg1 Bip 926:928 the ER chaperone Bip 909:928 the ER chaperone Bip 909:928 To adapt to NTZ-mediated ER stress, NTZ treated cells upregulated translation of Ca(2+)-binding proteins, including the ER chaperone Bip and the cytosolic pro-survival and anti-viral protein TCTP. 24971706 5 3 theme NTZ 829:831 arg1 cells 841:845 NTZ treated cells 829:845 NTZ treated cells 829:845 To adapt to NTZ-mediated ER stress, NTZ treated cells upregulated translation of Ca(2+)-binding proteins, including the ER chaperone Bip and the cytosolic pro-survival and anti-viral protein TCTP. 24971706 1 4 theme encephalitis 139:150 arg1 replication 187:197 influenza, Japanese encephalitis, hepatitis B and hepatitis C virus replication 119:197 influenza, Japanese encephalitis, hepatitis B and hepatitis C virus replication 119:197 Nitazoxanide (NTZ) inhibits influenza, Japanese encephalitis, hepatitis B and hepatitis C virus replication but effects on the replication of other members of the Flaviviridae family has yet to be defined. 24971706 6 5 theme antiviral 1105:1113 arg1 mechanisms 1115:1124 all antiviral mechanisms 1101:1124 all antiviral mechanisms attributed to the thiazolide 1101:1153 Depletion of intracellular Ca(2+) stores is the primary consequence of NTZ treatment and is likely to underpin all antiviral mechanisms attributed to the thiazolide. 24971706 4 6 theme glycosylation 762:774 arg1 perturbation 723:734 perturbation 723:734 induction of chronic sub-lethal ER stress as well as perturbation of viral protein N-linked glycosylation and trafficking 670:790 In addition to PKR and eIF2α phosphorylation, consequences of NTZ-mediated Ca(2+) mobilisation included induction of chronic sub-lethal ER stress as well as perturbation of viral protein N-linked glycosylation and trafficking. 24971706 4 6 theme glycosylation 762:774 arg1 induction 670:678 induction 670:678 induction of chronic sub-lethal ER stress as well as perturbation of viral protein N-linked glycosylation and trafficking 670:790 In addition to PKR and eIF2α phosphorylation, consequences of NTZ-mediated Ca(2+) mobilisation included induction of chronic sub-lethal ER stress as well as perturbation of viral protein N-linked glycosylation and trafficking. 24971706 4 7 theme ER 702:703 arg1 stress 705:710 chronic sub-lethal ER stress 683:710 chronic sub-lethal ER stress 683:710 In addition to PKR and eIF2α phosphorylation, consequences of NTZ-mediated Ca(2+) mobilisation included induction of chronic sub-lethal ER stress as well as perturbation of viral protein N-linked glycosylation and trafficking. 24971706 1 8 theme other 233:237 arg1 members 239:245 other members 233:245 other members of the Flaviviridae family 233:272 Nitazoxanide (NTZ) inhibits influenza, Japanese encephalitis, hepatitis B and hepatitis C virus replication but effects on the replication of other members of the Flaviviridae family has yet to be defined. 24971706 4 9 theme sub-lethal 691:700 arg1 stress 705:710 chronic sub-lethal ER stress 683:710 chronic sub-lethal ER stress 683:710 In addition to PKR and eIF2α phosphorylation, consequences of NTZ-mediated Ca(2+) mobilisation included induction of chronic sub-lethal ER stress as well as perturbation of viral protein N-linked glycosylation and trafficking. 24971706 2 10 theme viral 319:323 arg1 model 363:367 a surrogate model 351:367 a surrogate model for HCV infection 351:385 The pestivirus bovine viral diarrhoea virus (BVDV) is a surrogate model for HCV infection and NTZ induced PKR and eIF2α phosphorylation in both uninfected and BVDV-infected cells. 24971706 2 10 theme viral 319:323 arg1 BVDV 342:345 BVDV 342:345 BVDV 342:345 The pestivirus bovine viral diarrhoea virus (BVDV) is a surrogate model for HCV infection and NTZ induced PKR and eIF2α phosphorylation in both uninfected and BVDV-infected cells. 24971706 2 10 theme viral 319:323 arg1 virus 335:339 The pestivirus bovine viral diarrhoea virus 297:339 The pestivirus bovine viral diarrhoea virus (BVDV) 297:346 The pestivirus bovine viral diarrhoea virus (BVDV) is a surrogate model for HCV infection and NTZ induced PKR and eIF2α phosphorylation in both uninfected and BVDV-infected cells. 24971706 1 11 theme members 239:245 arg1 replication 218:228 the replication 214:228 the replication of other members of the Flaviviridae family 214:272 Nitazoxanide (NTZ) inhibits influenza, Japanese encephalitis, hepatitis B and hepatitis C virus replication but effects on the replication of other members of the Flaviviridae family has yet to be defined. 24971706 2 12 theme BVDV-infected 456:468 arg1 cells 470:474 both uninfected and BVDV-infected cells 436:474 both uninfected and BVDV-infected cells 436:474 The pestivirus bovine viral diarrhoea virus (BVDV) is a surrogate model for HCV infection and NTZ induced PKR and eIF2α phosphorylation in both uninfected and BVDV-infected cells. 24971706 6 13 theme primary 1038:1044 arg1 Depletion 990:998 Depletion 990:998 Depletion of intracellular Ca(2+) stores 990:1029 Depletion of intracellular Ca(2+) stores is the primary consequence of NTZ treatment and is likely to underpin all antiviral mechanisms attributed to the thiazolide. 24971706 6 13 theme primary 1038:1044 arg1 consequence 1046:1056 the primary consequence 1034:1056 the primary consequence of NTZ treatment 1034:1073 Depletion of intracellular Ca(2+) stores is the primary consequence of NTZ treatment and is likely to underpin all antiviral mechanisms attributed to the thiazolide. 24971706 4 14 theme trafficking 780:790 arg1 perturbation 723:734 perturbation 723:734 induction of chronic sub-lethal ER stress as well as perturbation of viral protein N-linked glycosylation and trafficking 670:790 In addition to PKR and eIF2α phosphorylation, consequences of NTZ-mediated Ca(2+) mobilisation included induction of chronic sub-lethal ER stress as well as perturbation of viral protein N-linked glycosylation and trafficking. 24971706 4 14 theme trafficking 780:790 arg1 induction 670:678 induction 670:678 induction of chronic sub-lethal ER stress as well as perturbation of viral protein N-linked glycosylation and trafficking 670:790 In addition to PKR and eIF2α phosphorylation, consequences of NTZ-mediated Ca(2+) mobilisation included induction of chronic sub-lethal ER stress as well as perturbation of viral protein N-linked glycosylation and trafficking. 24971706 5 15 theme NTZ-mediated 805:816 arg1 stress 821:826 NTZ-mediated ER stress 805:826 NTZ-mediated ER stress 805:826 To adapt to NTZ-mediated ER stress, NTZ treated cells upregulated translation of Ca(2+)-binding proteins, including the ER chaperone Bip and the cytosolic pro-survival and anti-viral protein TCTP. 24971706 4 16 theme eIF2α 589:593 arg1 phosphorylation 595:609 eIF2α phosphorylation 589:609 eIF2α phosphorylation 589:609 In addition to PKR and eIF2α phosphorylation, consequences of NTZ-mediated Ca(2+) mobilisation included induction of chronic sub-lethal ER stress as well as perturbation of viral protein N-linked glycosylation and trafficking. 24971706 5 17 theme treated 833:839 arg1 cells 841:845 NTZ treated cells 829:845 NTZ treated cells 829:845 To adapt to NTZ-mediated ER stress, NTZ treated cells upregulated translation of Ca(2+)-binding proteins, including the ER chaperone Bip and the cytosolic pro-survival and anti-viral protein TCTP. 24971706 4 18 theme stress 705:710 arg1 perturbation 723:734 perturbation 723:734 induction of chronic sub-lethal ER stress as well as perturbation of viral protein N-linked glycosylation and trafficking 670:790 In addition to PKR and eIF2α phosphorylation, consequences of NTZ-mediated Ca(2+) mobilisation included induction of chronic sub-lethal ER stress as well as perturbation of viral protein N-linked glycosylation and trafficking. 24971706 4 18 theme stress 705:710 arg1 induction 670:678 induction 670:678 induction of chronic sub-lethal ER stress as well as perturbation of viral protein N-linked glycosylation and trafficking 670:790 In addition to PKR and eIF2α phosphorylation, consequences of NTZ-mediated Ca(2+) mobilisation included induction of chronic sub-lethal ER stress as well as perturbation of viral protein N-linked glycosylation and trafficking. 24971706 6 19 theme Ca 1017:1018 arg1 stores 1024:1029 intracellular Ca(2+) stores 1003:1029 intracellular Ca(2+) stores 1003:1029 Depletion of intracellular Ca(2+) stores is the primary consequence of NTZ treatment and is likely to underpin all antiviral mechanisms attributed to the thiazolide. 24971706 1 20 theme hepatitis 153:161 arg1 B 163:163 hepatitis B 153:163 hepatitis B 153:163 Nitazoxanide (NTZ) inhibits influenza, Japanese encephalitis, hepatitis B and hepatitis C virus replication but effects on the replication of other members of the Flaviviridae family has yet to be defined. 24971706 2 21 theme uninfected 441:450 arg1 cells 470:474 both uninfected and BVDV-infected cells 436:474 both uninfected and BVDV-infected cells 436:474 The pestivirus bovine viral diarrhoea virus (BVDV) is a surrogate model for HCV infection and NTZ induced PKR and eIF2α phosphorylation in both uninfected and BVDV-infected cells. 24971706 6 22 theme treatment 1065:1073 arg1 Depletion 990:998 Depletion 990:998 Depletion of intracellular Ca(2+) stores 990:1029 Depletion of intracellular Ca(2+) stores is the primary consequence of NTZ treatment and is likely to underpin all antiviral mechanisms attributed to the thiazolide. 24971706 6 22 theme treatment 1065:1073 arg1 consequence 1046:1056 the primary consequence 1034:1056 the primary consequence of NTZ treatment 1034:1073 Depletion of intracellular Ca(2+) stores is the primary consequence of NTZ treatment and is likely to underpin all antiviral mechanisms attributed to the thiazolide. 24971706 1 23 theme B 163:163 arg1 replication 187:197 influenza, Japanese encephalitis, hepatitis B and hepatitis C virus replication 119:197 influenza, Japanese encephalitis, hepatitis B and hepatitis C virus replication 119:197 Nitazoxanide (NTZ) inhibits influenza, Japanese encephalitis, hepatitis B and hepatitis C virus replication but effects on the replication of other members of the Flaviviridae family has yet to be defined. 24971706 6 24 theme NTZ 1061:1063 arg1 treatment 1065:1073 NTZ treatment 1061:1073 NTZ treatment 1061:1073 Depletion of intracellular Ca(2+) stores is the primary consequence of NTZ treatment and is likely to underpin all antiviral mechanisms attributed to the thiazolide. 24971706 4 25 theme NTZ-mediated 628:639 arg1 2+ 644:645 2+ 644:645 2+ 644:645 In addition to PKR and eIF2α phosphorylation, consequences of NTZ-mediated Ca(2+) mobilisation included induction of chronic sub-lethal ER stress as well as perturbation of viral protein N-linked glycosylation and trafficking. 24971706 4 25 theme NTZ-mediated 628:639 arg1 Ca 641:642 NTZ-mediated Ca 628:642 NTZ-mediated Ca(2+) mobilisation 628:659 In addition to PKR and eIF2α phosphorylation, consequences of NTZ-mediated Ca(2+) mobilisation included induction of chronic sub-lethal ER stress as well as perturbation of viral protein N-linked glycosylation and trafficking. 24971706 0 26 theme antiviral 17:25 arg1 Nitazoxanide 0:11 Nitazoxanide 0:11 Nitazoxanide 0:11 Nitazoxanide, an antiviral thiazolide, depletes ATP-sensitive intracellular Ca(2+) stores. 24971706 0 26 theme antiviral 17:25 arg1 thiazolide 27:36 an antiviral thiazolide 14:36 an antiviral thiazolide 14:36 Nitazoxanide, an antiviral thiazolide, depletes ATP-sensitive intracellular Ca(2+) stores. 24971706 4 27 theme N-linked 753:760 arg1 glycosylation 762:774 viral protein N-linked glycosylation 739:774 viral protein N-linked glycosylation 739:774 In addition to PKR and eIF2α phosphorylation, consequences of NTZ-mediated Ca(2+) mobilisation included induction of chronic sub-lethal ER stress as well as perturbation of viral protein N-linked glycosylation and trafficking. 24971706 4 28 theme chronic 683:689 arg1 stress 705:710 chronic sub-lethal ER stress 683:710 chronic sub-lethal ER stress 683:710 In addition to PKR and eIF2α phosphorylation, consequences of NTZ-mediated Ca(2+) mobilisation included induction of chronic sub-lethal ER stress as well as perturbation of viral protein N-linked glycosylation and trafficking. 24971706 4 29 theme protein 745:751 arg1 glycosylation 762:774 viral protein N-linked glycosylation 739:774 viral protein N-linked glycosylation 739:774 In addition to PKR and eIF2α phosphorylation, consequences of NTZ-mediated Ca(2+) mobilisation included induction of chronic sub-lethal ER stress as well as perturbation of viral protein N-linked glycosylation and trafficking. 24971706 1 30 theme hepatitis 169:177 arg1 C 179:179 hepatitis C 169:179 hepatitis C 169:179 Nitazoxanide (NTZ) inhibits influenza, Japanese encephalitis, hepatitis B and hepatitis C virus replication but effects on the replication of other members of the Flaviviridae family has yet to be defined. 24971706 2 31 theme HCV 373:375 arg1 infection 377:385 HCV infection 373:385 HCV infection 373:385 The pestivirus bovine viral diarrhoea virus (BVDV) is a surrogate model for HCV infection and NTZ induced PKR and eIF2α phosphorylation in both uninfected and BVDV-infected cells. 24971706 1 32 theme Flaviviridae 254:265 arg1 family 267:272 the Flaviviridae family 250:272 the Flaviviridae family 250:272 Nitazoxanide (NTZ) inhibits influenza, Japanese encephalitis, hepatitis B and hepatitis C virus replication but effects on the replication of other members of the Flaviviridae family has yet to be defined. 24971706 2 33 theme bovine 312:317 arg1 model 363:367 a surrogate model 351:367 a surrogate model for HCV infection 351:385 The pestivirus bovine viral diarrhoea virus (BVDV) is a surrogate model for HCV infection and NTZ induced PKR and eIF2α phosphorylation in both uninfected and BVDV-infected cells. 24971706 2 33 theme bovine 312:317 arg1 BVDV 342:345 BVDV 342:345 BVDV 342:345 The pestivirus bovine viral diarrhoea virus (BVDV) is a surrogate model for HCV infection and NTZ induced PKR and eIF2α phosphorylation in both uninfected and BVDV-infected cells. 24971706 2 33 theme bovine 312:317 arg1 virus 335:339 The pestivirus bovine viral diarrhoea virus 297:339 The pestivirus bovine viral diarrhoea virus (BVDV) 297:346 The pestivirus bovine viral diarrhoea virus (BVDV) is a surrogate model for HCV infection and NTZ induced PKR and eIF2α phosphorylation in both uninfected and BVDV-infected cells. 24971706 5 34 theme cytosolic 938:946 arg1 protein 976:982 the cytosolic pro-survival and anti-viral protein 934:982 the cytosolic pro-survival and anti-viral protein TCTP 934:987 To adapt to NTZ-mediated ER stress, NTZ treated cells upregulated translation of Ca(2+)-binding proteins, including the ER chaperone Bip and the cytosolic pro-survival and anti-viral protein TCTP. 24971706 1 35 theme C 179:179 arg1 replication 187:197 influenza, Japanese encephalitis, hepatitis B and hepatitis C virus replication 119:197 influenza, Japanese encephalitis, hepatitis B and hepatitis C virus replication 119:197 Nitazoxanide (NTZ) inhibits influenza, Japanese encephalitis, hepatitis B and hepatitis C virus replication but effects on the replication of other members of the Flaviviridae family has yet to be defined. 24971706 2 36 theme eIF2α 411:415 arg1 phosphorylation 417:431 PKR and eIF2α phosphorylation 403:431 phosphorylation 417:431 The pestivirus bovine viral diarrhoea virus (BVDV) is a surrogate model for HCV infection and NTZ induced PKR and eIF2α phosphorylation in both uninfected and BVDV-infected cells. 24971706 1 37 theme family 267:272 arg1 members 239:245 other members 233:245 other members of the Flaviviridae family 233:272 Nitazoxanide (NTZ) inhibits influenza, Japanese encephalitis, hepatitis B and hepatitis C virus replication but effects on the replication of other members of the Flaviviridae family has yet to be defined. 24971706 1 38 theme virus 181:185 arg1 replication 187:197 influenza, Japanese encephalitis, hepatitis B and hepatitis C virus replication 119:197 influenza, Japanese encephalitis, hepatitis B and hepatitis C virus replication 119:197 Nitazoxanide (NTZ) inhibits influenza, Japanese encephalitis, hepatitis B and hepatitis C virus replication but effects on the replication of other members of the Flaviviridae family has yet to be defined. 24971706 3 39 theme Ca 551:552 arg1 stores 558:563 ATP-sensitive intracellular Ca(2+) stores 523:563 ATP-sensitive intracellular Ca(2+) stores 523:563 This led to the observation that NTZ depletes ATP-sensitive intracellular Ca(2+) stores. 24971706 5 40 theme ER 818:819 arg1 stress 821:826 NTZ-mediated ER stress 805:826 NTZ-mediated ER stress 805:826 To adapt to NTZ-mediated ER stress, NTZ treated cells upregulated translation of Ca(2+)-binding proteins, including the ER chaperone Bip and the cytosolic pro-survival and anti-viral protein TCTP. 24971706 2 41 theme surrogate 353:361 arg1 model 363:367 a surrogate model 351:367 a surrogate model for HCV infection 351:385 The pestivirus bovine viral diarrhoea virus (BVDV) is a surrogate model for HCV infection and NTZ induced PKR and eIF2α phosphorylation in both uninfected and BVDV-infected cells. 24971706 2 41 theme surrogate 353:361 arg1 virus 335:339 The pestivirus bovine viral diarrhoea virus 297:339 The pestivirus bovine viral diarrhoea virus (BVDV) 297:346 The pestivirus bovine viral diarrhoea virus (BVDV) is a surrogate model for HCV infection and NTZ induced PKR and eIF2α phosphorylation in both uninfected and BVDV-infected cells. 24971706 6 42 theme intracellular 1003:1015 arg1 stores 1024:1029 intracellular Ca(2+) stores 1003:1029 intracellular Ca(2+) stores 1003:1029 Depletion of intracellular Ca(2+) stores is the primary consequence of NTZ treatment and is likely to underpin all antiviral mechanisms attributed to the thiazolide. 24971706 4 43 theme viral 739:743 arg1 glycosylation 762:774 viral protein N-linked glycosylation 739:774 viral protein N-linked glycosylation 739:774 In addition to PKR and eIF2α phosphorylation, consequences of NTZ-mediated Ca(2+) mobilisation included induction of chronic sub-lethal ER stress as well as perturbation of viral protein N-linked glycosylation and trafficking. 24971706 0 44 theme ATP-sensitive 48:60 arg1 2+ 79:80 2+ 79:80 2+ 79:80 Nitazoxanide, an antiviral thiazolide, depletes ATP-sensitive intracellular Ca(2+) stores. 24971706 0 44 theme ATP-sensitive 48:60 arg1 Ca 76:77 ATP-sensitive intracellular Ca 48:77 ATP-sensitive intracellular Ca(2+) stores 48:88 Nitazoxanide, an antiviral thiazolide, depletes ATP-sensitive intracellular Ca(2+) stores. 24971706 0 45 theme intracellular 62:74 arg1 2+ 79:80 2+ 79:80 2+ 79:80 Nitazoxanide, an antiviral thiazolide, depletes ATP-sensitive intracellular Ca(2+) stores. 24971706 0 45 theme intracellular 62:74 arg1 Ca 76:77 ATP-sensitive intracellular Ca 48:77 ATP-sensitive intracellular Ca(2+) stores 48:88 Nitazoxanide, an antiviral thiazolide, depletes ATP-sensitive intracellular Ca(2+) stores. 24971706 3 46 theme ATP-sensitive 523:535 arg1 Ca 551:552 ATP-sensitive intracellular Ca 523:552 ATP-sensitive intracellular Ca(2+) stores 523:563 This led to the observation that NTZ depletes ATP-sensitive intracellular Ca(2+) stores. 24971706 3 46 theme ATP-sensitive 523:535 arg1 2+ 554:555 2+ 554:555 2+ 554:555 This led to the observation that NTZ depletes ATP-sensitive intracellular Ca(2+) stores. 24971706 2 47 theme pestivirus 301:310 arg1 model 363:367 a surrogate model 351:367 a surrogate model for HCV infection 351:385 The pestivirus bovine viral diarrhoea virus (BVDV) is a surrogate model for HCV infection and NTZ induced PKR and eIF2α phosphorylation in both uninfected and BVDV-infected cells. 24971706 2 47 theme pestivirus 301:310 arg1 BVDV 342:345 BVDV 342:345 BVDV 342:345 The pestivirus bovine viral diarrhoea virus (BVDV) is a surrogate model for HCV infection and NTZ induced PKR and eIF2α phosphorylation in both uninfected and BVDV-infected cells. 24971706 2 47 theme pestivirus 301:310 arg1 virus 335:339 The pestivirus bovine viral diarrhoea virus 297:339 The pestivirus bovine viral diarrhoea virus (BVDV) 297:346 The pestivirus bovine viral diarrhoea virus (BVDV) is a surrogate model for HCV infection and NTZ induced PKR and eIF2α phosphorylation in both uninfected and BVDV-infected cells. 24971706 5 48 theme pro-survival 948:959 arg1 protein 976:982 the cytosolic pro-survival and anti-viral protein 934:982 the cytosolic pro-survival and anti-viral protein TCTP 934:987 To adapt to NTZ-mediated ER stress, NTZ treated cells upregulated translation of Ca(2+)-binding proteins, including the ER chaperone Bip and the cytosolic pro-survival and anti-viral protein TCTP. 24971706 3 49 theme intracellular 537:549 arg1 Ca 551:552 ATP-sensitive intracellular Ca 523:552 ATP-sensitive intracellular Ca(2+) stores 523:563 This led to the observation that NTZ depletes ATP-sensitive intracellular Ca(2+) stores. 24971706 3 49 theme intracellular 537:549 arg1 2+ 554:555 2+ 554:555 2+ 554:555 This led to the observation that NTZ depletes ATP-sensitive intracellular Ca(2+) stores. 24971706 5 50 theme anti-viral 965:974 arg1 protein 976:982 the cytosolic pro-survival and anti-viral protein 934:982 the cytosolic pro-survival and anti-viral protein TCTP 934:987 To adapt to NTZ-mediated ER stress, NTZ treated cells upregulated translation of Ca(2+)-binding proteins, including the ER chaperone Bip and the cytosolic pro-survival and anti-viral protein TCTP. 24971706 4 51 theme mobilisation 648:659 arg1 consequences 612:623 consequences 612:623 consequences of NTZ-mediated Ca(2+) mobilisation 612:659 In addition to PKR and eIF2α phosphorylation, consequences of NTZ-mediated Ca(2+) mobilisation included induction of chronic sub-lethal ER stress as well as perturbation of viral protein N-linked glycosylation and trafficking. 24971706 6 52 theme stores 1024:1029 arg1 Depletion 990:998 Depletion 990:998 Depletion of intracellular Ca(2+) stores 990:1029 Depletion of intracellular Ca(2+) stores is the primary consequence of NTZ treatment and is likely to underpin all antiviral mechanisms attributed to the thiazolide. 24971706 6 52 theme stores 1024:1029 arg1 consequence 1046:1056 the primary consequence 1034:1056 the primary consequence of NTZ treatment 1034:1073 Depletion of intracellular Ca(2+) stores is the primary consequence of NTZ treatment and is likely to underpin all antiviral mechanisms attributed to the thiazolide. 24971706 1 53 from effects 203:209 arg1 replication 218:228 the replication 214:228 the replication of other members of the Flaviviridae family 214:272 Nitazoxanide (NTZ) inhibits influenza, Japanese encephalitis, hepatitis B and hepatitis C virus replication but effects on the replication of other members of the Flaviviridae family has yet to be defined. 24971706 5 54 theme protein 976:982 arg1 TCTP 984:987 the cytosolic pro-survival and anti-viral protein TCTP 934:987 the cytosolic pro-survival and anti-viral protein TCTP 934:987 To adapt to NTZ-mediated ER stress, NTZ treated cells upregulated translation of Ca(2+)-binding proteins, including the ER chaperone Bip and the cytosolic pro-survival and anti-viral protein TCTP. 24971706 5 55 theme ER 913:914 arg1 Bip 926:928 the ER chaperone Bip 909:928 the ER chaperone Bip 909:928 To adapt to NTZ-mediated ER stress, NTZ treated cells upregulated translation of Ca(2+)-binding proteins, including the ER chaperone Bip and the cytosolic pro-survival and anti-viral protein TCTP. 24971706 6 56 theme 2+ 1020:1021 arg1 stores 1024:1029 intracellular Ca(2+) stores 1003:1029 intracellular Ca(2+) stores 1003:1029 Depletion of intracellular Ca(2+) stores is the primary consequence of NTZ treatment and is likely to underpin all antiviral mechanisms attributed to the thiazolide. 24971706 0 57 theme Ca 76:77 arg1 stores 83:88 ATP-sensitive intracellular Ca(2+) stores 48:88 ATP-sensitive intracellular Ca(2+) stores 48:88 Nitazoxanide, an antiviral thiazolide, depletes ATP-sensitive intracellular Ca(2+) stores. 24971706 5 58 theme chaperone 916:924 arg1 Bip 926:928 the ER chaperone Bip 909:928 the ER chaperone Bip 909:928 To adapt to NTZ-mediated ER stress, NTZ treated cells upregulated translation of Ca(2+)-binding proteins, including the ER chaperone Bip and the cytosolic pro-survival and anti-viral protein TCTP. 24971706 1 59 theme influenza 119:127 arg1 replication 187:197 influenza, Japanese encephalitis, hepatitis B and hepatitis C virus replication 119:197 influenza, Japanese encephalitis, hepatitis B and hepatitis C virus replication 119:197 Nitazoxanide (NTZ) inhibits influenza, Japanese encephalitis, hepatitis B and hepatitis C virus replication but effects on the replication of other members of the Flaviviridae family has yet to be defined. 24971706 4 60 link N-linked 753:760 arg1 glycosylation 762:774 viral protein N-linked glycosylation 739:774 viral protein N-linked glycosylation 739:774 In addition to PKR and eIF2α phosphorylation, consequences of NTZ-mediated Ca(2+) mobilisation included induction of chronic sub-lethal ER stress as well as perturbation of viral protein N-linked glycosylation and trafficking. 24971706 2 61 theme PKR 403:405 arg1 phosphorylation 417:431 PKR and eIF2α phosphorylation 403:431 phosphorylation 417:431 The pestivirus bovine viral diarrhoea virus (BVDV) is a surrogate model for HCV infection and NTZ induced PKR and eIF2α phosphorylation in both uninfected and BVDV-infected cells. 24971706 5 62 theme proteins 889:896 arg1 translation 859:869 translation 859:869 translation of Ca(2+)-binding proteins, including the ER chaperone Bip and the cytosolic pro-survival and anti-viral protein TCTP 859:987 To adapt to NTZ-mediated ER stress, NTZ treated cells upregulated translation of Ca(2+)-binding proteins, including the ER chaperone Bip and the cytosolic pro-survival and anti-viral protein TCTP. 24971706 2 63 theme diarrhoea 325:333 arg1 model 363:367 a surrogate model 351:367 a surrogate model for HCV infection 351:385 The pestivirus bovine viral diarrhoea virus (BVDV) is a surrogate model for HCV infection and NTZ induced PKR and eIF2α phosphorylation in both uninfected and BVDV-infected cells. 24971706 2 63 theme diarrhoea 325:333 arg1 BVDV 342:345 BVDV 342:345 BVDV 342:345 The pestivirus bovine viral diarrhoea virus (BVDV) is a surrogate model for HCV infection and NTZ induced PKR and eIF2α phosphorylation in both uninfected and BVDV-infected cells. 24971706 2 63 theme diarrhoea 325:333 arg1 virus 335:339 The pestivirus bovine viral diarrhoea virus 297:339 The pestivirus bovine viral diarrhoea virus (BVDV) 297:346 The pestivirus bovine viral diarrhoea virus (BVDV) is a surrogate model for HCV infection and NTZ induced PKR and eIF2α phosphorylation in both uninfected and BVDV-infected cells. 25173615 4 0 link N-linked 607:614 arg1 complex 680:686 complex 680:686 complex 680:686 The N-linked glycosylation profile of the murine IgG1 was found to be highly complex since it included terminal galactosylation and sialylation, as well as variable core-fucosylation. 25173615 4 0 link N-linked 607:614 arg1 profile 630:636 The N-linked glycosylation profile 603:636 The N-linked glycosylation profile of the murine IgG1 603:655 The N-linked glycosylation profile of the murine IgG1 was found to be highly complex since it included terminal galactosylation and sialylation, as well as variable core-fucosylation. 25173615 3 1 from effect 424:429 arg1 microheterogeneity 510:527 the glycan microheterogeneity 499:527 the glycan microheterogeneity of an IgG1 antibody 499:547 In this study we investigated the effect of single and combined chemical and mechanical stress parameters on the glycan microheterogeneity of an IgG1 antibody using a shift-experiment procedure in batch cultures. 25173615 6 2 theme % 946:946 arg1 saturation 952:961 10-90% air saturation 941:961 10-90% air saturation 941:961 Variation of dissolved oxygen tension (10-90% air saturation) resulted in a maximum variability of 20% in galactosylation and 30% in sialylation. 25173615 6 2 theme % 946:946 arg1 tension 932:938 dissolved oxygen tension 915:938 dissolved oxygen tension (10-90% air saturation) 915:962 Variation of dissolved oxygen tension (10-90% air saturation) resulted in a maximum variability of 20% in galactosylation and 30% in sialylation. 25173615 4 3 theme murine 645:650 arg1 IgG1 652:655 the murine IgG1 641:655 the murine IgG1 641:655 The N-linked glycosylation profile of the murine IgG1 was found to be highly complex since it included terminal galactosylation and sialylation, as well as variable core-fucosylation. 25173615 1 4 theme antibodies 199:208 arg1 profile 164:170 the N-linked glycosylation profile 137:170 the N-linked glycosylation profile of the produced monoclonal antibodies 137:208 Bioreactor process parameters influence the N-linked glycosylation profile of the produced monoclonal antibodies. 25173615 6 5 theme oxygen 925:930 arg1 saturation 952:961 10-90% air saturation 941:961 10-90% air saturation 941:961 Variation of dissolved oxygen tension (10-90% air saturation) resulted in a maximum variability of 20% in galactosylation and 30% in sialylation. 25173615 6 5 theme oxygen 925:930 arg1 tension 932:938 dissolved oxygen tension 915:938 dissolved oxygen tension (10-90% air saturation) 915:962 Variation of dissolved oxygen tension (10-90% air saturation) resulted in a maximum variability of 20% in galactosylation and 30% in sialylation. 25173615 5 6 dep 7.8 815:817 arg1 to 812:813 to 812:813 to 812:813 Within a pH range of 6.8 to 7.8 differences in galactosylation and sialylation of approximately 50% were obtained. 25173615 8 7 theme bioprocess-related 1250:1267 arg1 factors 1269:1275 bioprocess-related factors 1250:1275 bioprocess-related factors affecting critical quality attributes under the scope of QbD 1250:1336 In this study a better understanding of bioprocess-related factors affecting critical quality attributes under the scope of QbD is provided and can bring us one step closer towards desired and targeted glycosylation for future therapeutic proteins. 25173615 2 8 theme critical 335:342 arg1 attributes 352:361 the most critical quality attributes 326:361 the most critical quality attributes of therapeutic antibodies 326:387 A systematic assessment of their impact is a prerequisite for providing controllability over glycosylation, one of the most critical quality attributes of therapeutic antibodies. 25173615 5 9 theme % 885:885 arg1 sialylation 854:864 sialylation 854:864 sialylation 854:864 Within a pH range of 6.8 to 7.8 differences in galactosylation and sialylation of approximately 50% were obtained. 25173615 5 9 theme % 885:885 arg1 galactosylation 834:848 galactosylation 834:848 galactosylation 834:848 Within a pH range of 6.8 to 7.8 differences in galactosylation and sialylation of approximately 50% were obtained. 25173615 8 10 theme quality 1296:1302 arg1 attributes 1304:1313 critical quality attributes 1287:1313 critical quality attributes 1287:1313 In this study a better understanding of bioprocess-related factors affecting critical quality attributes under the scope of QbD is provided and can bring us one step closer towards desired and targeted glycosylation for future therapeutic proteins. 25173615 2 11 theme impact 244:249 arg1 assessment 224:233 A systematic assessment 211:233 A systematic assessment of their impact 211:249 A systematic assessment of their impact is a prerequisite for providing controllability over glycosylation, one of the most critical quality attributes of therapeutic antibodies. 25173615 2 11 theme impact 244:249 arg1 prerequisite 256:267 a prerequisite 254:267 a prerequisite for providing controllability over glycosylation, one of the most critical quality attributes of therapeutic antibodies 254:387 A systematic assessment of their impact is a prerequisite for providing controllability over glycosylation, one of the most critical quality attributes of therapeutic antibodies. 25173615 5 12 from range 799:803 arg1 sialylation 854:864 sialylation 854:864 sialylation 854:864 Within a pH range of 6.8 to 7.8 differences in galactosylation and sialylation of approximately 50% were obtained. 25173615 5 12 from range 799:803 arg1 galactosylation 834:848 galactosylation 834:848 galactosylation 834:848 Within a pH range of 6.8 to 7.8 differences in galactosylation and sialylation of approximately 50% were obtained. 25173615 1 13 theme glycosylation 150:162 arg1 profile 164:170 the N-linked glycosylation profile 137:170 the N-linked glycosylation profile of the produced monoclonal antibodies 137:208 Bioreactor process parameters influence the N-linked glycosylation profile of the produced monoclonal antibodies. 25173615 8 14 theme QbD 1334:1336 arg1 scope 1325:1329 the scope 1321:1329 the scope of QbD 1321:1336 In this study a better understanding of bioprocess-related factors affecting critical quality attributes under the scope of QbD is provided and can bring us one step closer towards desired and targeted glycosylation for future therapeutic proteins. 25173615 6 15 theme % 1030:1030 arg1 variability 986:996 a maximum variability 976:996 a maximum variability of 20% in galactosylation and 30% in sialylation 976:1045 Variation of dissolved oxygen tension (10-90% air saturation) resulted in a maximum variability of 20% in galactosylation and 30% in sialylation. 25173615 0 16 from impact 15:20 arg1 N-glycosylation 80:94 monoclonal antibody N-glycosylation 60:94 monoclonal antibody N-glycosylation 60:94 Evaluating the impact of cell culture process parameters on monoclonal antibody N-glycosylation. 25173615 0 17 theme antibody 71:78 arg1 N-glycosylation 80:94 monoclonal antibody N-glycosylation 60:94 monoclonal antibody N-glycosylation 60:94 Evaluating the impact of cell culture process parameters on monoclonal antibody N-glycosylation. 25173615 1 18 theme produced 179:186 arg1 antibodies 199:208 the produced monoclonal antibodies 175:208 the produced monoclonal antibodies 175:208 Bioreactor process parameters influence the N-linked glycosylation profile of the produced monoclonal antibodies. 25173615 3 19 gly microheterogeneity 510:527 arg1 antibody 540:547 an IgG1 antibody 532:547 an IgG1 antibody 532:547 In this study we investigated the effect of single and combined chemical and mechanical stress parameters on the glycan microheterogeneity of an IgG1 antibody using a shift-experiment procedure in batch cultures. 25173615 6 20 from galactosylation 1008:1022 arg1 variability 986:996 a maximum variability 976:996 a maximum variability of 20% in galactosylation and 30% in sialylation 976:1045 Variation of dissolved oxygen tension (10-90% air saturation) resulted in a maximum variability of 20% in galactosylation and 30% in sialylation. 25173615 3 21 theme mechanical 467:476 arg1 parameters 485:494 single and combined chemical and mechanical stress parameters 434:494 single and combined chemical and mechanical stress parameters 434:494 In this study we investigated the effect of single and combined chemical and mechanical stress parameters on the glycan microheterogeneity of an IgG1 antibody using a shift-experiment procedure in batch cultures. 25173615 5 22 theme pH 796:797 arg1 range 799:803 a pH range 794:803 a pH range of 6.8 to 7.8 differences in galactosylation and sialylation of approximately 50% 794:885 Within a pH range of 6.8 to 7.8 differences in galactosylation and sialylation of approximately 50% were obtained. 25173615 7 23 dep 420 1163:1165 arg1 to 1160:1161 to 1160:1161 to 1160:1161 In contrast, no significant effect on the glycosylation profile was observed when osmolarity increased from 320 to 420 mOsm/kg and sparging from 0.05 to 0.2 vvm. 25173615 3 24 theme chemical 454:461 arg1 parameters 485:494 single and combined chemical and mechanical stress parameters 434:494 single and combined chemical and mechanical stress parameters 434:494 In this study we investigated the effect of single and combined chemical and mechanical stress parameters on the glycan microheterogeneity of an IgG1 antibody using a shift-experiment procedure in batch cultures. 25173615 1 25 theme Bioreactor 97:106 arg1 parameters 116:125 Bioreactor process parameters 97:125 Bioreactor process parameters 97:125 Bioreactor process parameters influence the N-linked glycosylation profile of the produced monoclonal antibodies. 25173615 6 26 theme dissolved 915:923 arg1 saturation 952:961 10-90% air saturation 941:961 10-90% air saturation 941:961 Variation of dissolved oxygen tension (10-90% air saturation) resulted in a maximum variability of 20% in galactosylation and 30% in sialylation. 25173615 6 26 theme dissolved 915:923 arg1 tension 932:938 dissolved oxygen tension 915:938 dissolved oxygen tension (10-90% air saturation) 915:962 Variation of dissolved oxygen tension (10-90% air saturation) resulted in a maximum variability of 20% in galactosylation and 30% in sialylation. 25173615 4 27 theme N-linked 607:614 arg1 complex 680:686 complex 680:686 complex 680:686 The N-linked glycosylation profile of the murine IgG1 was found to be highly complex since it included terminal galactosylation and sialylation, as well as variable core-fucosylation. 25173615 4 27 theme N-linked 607:614 arg1 profile 630:636 The N-linked glycosylation profile 603:636 The N-linked glycosylation profile of the murine IgG1 603:655 The N-linked glycosylation profile of the murine IgG1 was found to be highly complex since it included terminal galactosylation and sialylation, as well as variable core-fucosylation. 25173615 6 28 from % 1003:1003 arg1 sialylation 1035:1045 sialylation 1035:1045 sialylation 1035:1045 Variation of dissolved oxygen tension (10-90% air saturation) resulted in a maximum variability of 20% in galactosylation and 30% in sialylation. 25173615 6 28 from % 1003:1003 arg1 galactosylation 1008:1022 galactosylation 1008:1022 galactosylation 1008:1022 Variation of dissolved oxygen tension (10-90% air saturation) resulted in a maximum variability of 20% in galactosylation and 30% in sialylation. 25173615 5 29 gly sialylation 854:864 arg1 % 885:885 approximately 50% 869:885 approximately 50% 869:885 Within a pH range of 6.8 to 7.8 differences in galactosylation and sialylation of approximately 50% were obtained. 25173615 3 30 theme parameters 485:494 arg1 effect 424:429 the effect 420:429 the effect of single and combined chemical and mechanical stress parameters on the glycan microheterogeneity of an IgG1 antibody 420:547 In this study we investigated the effect of single and combined chemical and mechanical stress parameters on the glycan microheterogeneity of an IgG1 antibody using a shift-experiment procedure in batch cultures. 25173615 0 31 theme cell 25:28 arg1 parameters 46:55 cell culture process parameters 25:55 cell culture process parameters 25:55 Evaluating the impact of cell culture process parameters on monoclonal antibody N-glycosylation. 25173615 5 32 theme differences 819:829 arg1 range 799:803 a pH range 794:803 a pH range of 6.8 to 7.8 differences in galactosylation and sialylation of approximately 50% 794:885 Within a pH range of 6.8 to 7.8 differences in galactosylation and sialylation of approximately 50% were obtained. 25173615 1 33 link N-linked 141:148 arg1 profile 164:170 the N-linked glycosylation profile 137:170 the N-linked glycosylation profile of the produced monoclonal antibodies 137:208 Bioreactor process parameters influence the N-linked glycosylation profile of the produced monoclonal antibodies. 25173615 2 34 theme antibodies 378:387 arg1 attributes 352:361 the most critical quality attributes 326:361 the most critical quality attributes of therapeutic antibodies 326:387 A systematic assessment of their impact is a prerequisite for providing controllability over glycosylation, one of the most critical quality attributes of therapeutic antibodies. 25173615 0 35 theme process 38:44 arg1 parameters 46:55 cell culture process parameters 25:55 cell culture process parameters 25:55 Evaluating the impact of cell culture process parameters on monoclonal antibody N-glycosylation. 25173615 8 36 theme future 1430:1435 arg1 proteins 1449:1456 future therapeutic proteins 1430:1456 future therapeutic proteins 1430:1456 In this study a better understanding of bioprocess-related factors affecting critical quality attributes under the scope of QbD is provided and can bring us one step closer towards desired and targeted glycosylation for future therapeutic proteins. 25173615 4 37 theme IgG1 652:655 arg1 complex 680:686 complex 680:686 complex 680:686 The N-linked glycosylation profile of the murine IgG1 was found to be highly complex since it included terminal galactosylation and sialylation, as well as variable core-fucosylation. 25173615 4 37 theme IgG1 652:655 arg1 profile 630:636 The N-linked glycosylation profile 603:636 The N-linked glycosylation profile of the murine IgG1 603:655 The N-linked glycosylation profile of the murine IgG1 was found to be highly complex since it included terminal galactosylation and sialylation, as well as variable core-fucosylation. 25173615 2 38 theme systematic 213:222 arg1 assessment 224:233 A systematic assessment 211:233 A systematic assessment of their impact 211:249 A systematic assessment of their impact is a prerequisite for providing controllability over glycosylation, one of the most critical quality attributes of therapeutic antibodies. 25173615 2 38 theme systematic 213:222 arg1 prerequisite 256:267 a prerequisite 254:267 a prerequisite for providing controllability over glycosylation, one of the most critical quality attributes of therapeutic antibodies 254:387 A systematic assessment of their impact is a prerequisite for providing controllability over glycosylation, one of the most critical quality attributes of therapeutic antibodies. 25173615 3 39 theme antibody 540:547 arg1 microheterogeneity 510:527 the glycan microheterogeneity 499:527 the glycan microheterogeneity of an IgG1 antibody 499:547 In this study we investigated the effect of single and combined chemical and mechanical stress parameters on the glycan microheterogeneity of an IgG1 antibody using a shift-experiment procedure in batch cultures. 25173615 6 40 theme air 948:950 arg1 saturation 952:961 10-90% air saturation 941:961 10-90% air saturation 941:961 Variation of dissolved oxygen tension (10-90% air saturation) resulted in a maximum variability of 20% in galactosylation and 30% in sialylation. 25173615 6 40 theme air 948:950 arg1 tension 932:938 dissolved oxygen tension 915:938 dissolved oxygen tension (10-90% air saturation) 915:962 Variation of dissolved oxygen tension (10-90% air saturation) resulted in a maximum variability of 20% in galactosylation and 30% in sialylation. 25173615 7 41 from effect 1076:1081 arg1 profile 1104:1110 the glycosylation profile 1086:1110 the glycosylation profile 1086:1110 In contrast, no significant effect on the glycosylation profile was observed when osmolarity increased from 320 to 420 mOsm/kg and sparging from 0.05 to 0.2 vvm. 25173615 3 42 theme batch 587:591 arg1 cultures 593:600 batch cultures 587:600 batch cultures 587:600 In this study we investigated the effect of single and combined chemical and mechanical stress parameters on the glycan microheterogeneity of an IgG1 antibody using a shift-experiment procedure in batch cultures. 25173615 6 43 theme 10-90 941:945 arg1 % 946:946 % 946:946 % 946:946 Variation of dissolved oxygen tension (10-90% air saturation) resulted in a maximum variability of 20% in galactosylation and 30% in sialylation. 25173615 1 44 theme monoclonal 188:197 arg1 antibodies 199:208 the produced monoclonal antibodies 175:208 the produced monoclonal antibodies 175:208 Bioreactor process parameters influence the N-linked glycosylation profile of the produced monoclonal antibodies. 25173615 6 45 theme tension 932:938 arg1 Variation 902:910 Variation 902:910 Variation of dissolved oxygen tension (10-90% air saturation) 902:962 Variation of dissolved oxygen tension (10-90% air saturation) resulted in a maximum variability of 20% in galactosylation and 30% in sialylation. 25173615 8 46 theme better 1226:1231 arg1 understanding 1233:1245 a better understanding 1224:1245 a better understanding of bioprocess-related factors affecting critical quality attributes under the scope of QbD 1224:1336 In this study a better understanding of bioprocess-related factors affecting critical quality attributes under the scope of QbD is provided and can bring us one step closer towards desired and targeted glycosylation for future therapeutic proteins. 25173615 7 47 theme glycosylation 1090:1102 arg1 profile 1104:1110 the glycosylation profile 1086:1110 the glycosylation profile 1086:1110 In contrast, no significant effect on the glycosylation profile was observed when osmolarity increased from 320 to 420 mOsm/kg and sparging from 0.05 to 0.2 vvm. 25173615 2 48 theme quality 344:350 arg1 attributes 352:361 the most critical quality attributes 326:361 the most critical quality attributes of therapeutic antibodies 326:387 A systematic assessment of their impact is a prerequisite for providing controllability over glycosylation, one of the most critical quality attributes of therapeutic antibodies. 25173615 6 49 theme % 1003:1003 arg1 variability 986:996 a maximum variability 976:996 a maximum variability of 20% in galactosylation and 30% in sialylation 976:1045 Variation of dissolved oxygen tension (10-90% air saturation) resulted in a maximum variability of 20% in galactosylation and 30% in sialylation. 25173615 4 50 theme terminal 706:713 arg1 galactosylation 715:729 terminal galactosylation 706:729 terminal galactosylation 706:729 The N-linked glycosylation profile of the murine IgG1 was found to be highly complex since it included terminal galactosylation and sialylation, as well as variable core-fucosylation. 25173615 8 51 dep us 1364:1365 arg1 step 1371:1374 one step 1367:1374 us one step closer towards desired and targeted glycosylation for future therapeutic proteins 1364:1456 In this study a better understanding of bioprocess-related factors affecting critical quality attributes under the scope of QbD is provided and can bring us one step closer towards desired and targeted glycosylation for future therapeutic proteins. 25173615 8 52 theme factors 1269:1275 arg1 understanding 1233:1245 a better understanding 1224:1245 a better understanding of bioprocess-related factors affecting critical quality attributes under the scope of QbD 1224:1336 In this study a better understanding of bioprocess-related factors affecting critical quality attributes under the scope of QbD is provided and can bring us one step closer towards desired and targeted glycosylation for future therapeutic proteins. 25173615 2 53 theme therapeutic 366:376 arg1 antibodies 378:387 therapeutic antibodies 366:387 therapeutic antibodies 366:387 A systematic assessment of their impact is a prerequisite for providing controllability over glycosylation, one of the most critical quality attributes of therapeutic antibodies. 25173615 7 54 theme significant 1064:1074 arg1 effect 1076:1081 no significant effect 1061:1081 no significant effect on the glycosylation profile 1061:1110 In contrast, no significant effect on the glycosylation profile was observed when osmolarity increased from 320 to 420 mOsm/kg and sparging from 0.05 to 0.2 vvm. 25173615 6 55 theme maximum 978:984 arg1 variability 986:996 a maximum variability 976:996 a maximum variability of 20% in galactosylation and 30% in sialylation 976:1045 Variation of dissolved oxygen tension (10-90% air saturation) resulted in a maximum variability of 20% in galactosylation and 30% in sialylation. 25173615 8 56 theme critical 1287:1294 arg1 attributes 1304:1313 critical quality attributes 1287:1313 critical quality attributes 1287:1313 In this study a better understanding of bioprocess-related factors affecting critical quality attributes under the scope of QbD is provided and can bring us one step closer towards desired and targeted glycosylation for future therapeutic proteins. 25173615 7 57 located observed 1116:1123 arg2 effect 1076:1081 no significant effect 1061:1081 no significant effect on the glycosylation profile 1061:1110 In contrast, no significant effect on the glycosylation profile was observed when osmolarity increased from 320 to 420 mOsm/kg and sparging from 0.05 to 0.2 vvm. 25173615 7 57 located observed 1116:1123 arg1 contrast 1051:1058 contrast 1051:1058 contrast 1051:1058 In contrast, no significant effect on the glycosylation profile was observed when osmolarity increased from 320 to 420 mOsm/kg and sparging from 0.05 to 0.2 vvm. 25173615 4 58 gly glycosylation 616:628 arg1 IgG1 652:655 the murine IgG1 641:655 the murine IgG1 641:655 The N-linked glycosylation profile of the murine IgG1 was found to be highly complex since it included terminal galactosylation and sialylation, as well as variable core-fucosylation. 25173615 1 59 theme N-linked 141:148 arg1 profile 164:170 the N-linked glycosylation profile 137:170 the N-linked glycosylation profile of the produced monoclonal antibodies 137:208 Bioreactor process parameters influence the N-linked glycosylation profile of the produced monoclonal antibodies. 25173615 4 60 theme variable 759:766 arg1 core-fucosylation 768:784 variable core-fucosylation 759:784 variable core-fucosylation 759:784 The N-linked glycosylation profile of the murine IgG1 was found to be highly complex since it included terminal galactosylation and sialylation, as well as variable core-fucosylation. 25173615 0 61 theme monoclonal 60:69 arg1 N-glycosylation 80:94 monoclonal antibody N-glycosylation 60:94 monoclonal antibody N-glycosylation 60:94 Evaluating the impact of cell culture process parameters on monoclonal antibody N-glycosylation. 25173615 3 62 from procedure 574:582 arg1 cultures 593:600 batch cultures 587:600 batch cultures 587:600 In this study we investigated the effect of single and combined chemical and mechanical stress parameters on the glycan microheterogeneity of an IgG1 antibody using a shift-experiment procedure in batch cultures. 25173615 5 63 from galactosylation 834:848 arg1 range 799:803 a pH range 794:803 a pH range of 6.8 to 7.8 differences in galactosylation and sialylation of approximately 50% 794:885 Within a pH range of 6.8 to 7.8 differences in galactosylation and sialylation of approximately 50% were obtained. 25173615 6 64 from % 1030:1030 arg1 sialylation 1035:1045 sialylation 1035:1045 sialylation 1035:1045 Variation of dissolved oxygen tension (10-90% air saturation) resulted in a maximum variability of 20% in galactosylation and 30% in sialylation. 25173615 6 64 from % 1030:1030 arg1 galactosylation 1008:1022 galactosylation 1008:1022 galactosylation 1008:1022 Variation of dissolved oxygen tension (10-90% air saturation) resulted in a maximum variability of 20% in galactosylation and 30% in sialylation. 25173615 5 65 from differences 819:829 arg1 sialylation 854:864 sialylation 854:864 sialylation 854:864 Within a pH range of 6.8 to 7.8 differences in galactosylation and sialylation of approximately 50% were obtained. 25173615 5 65 from differences 819:829 arg1 galactosylation 834:848 galactosylation 834:848 galactosylation 834:848 Within a pH range of 6.8 to 7.8 differences in galactosylation and sialylation of approximately 50% were obtained. 25173615 6 66 from sialylation 1035:1045 arg1 variability 986:996 a maximum variability 976:996 a maximum variability of 20% in galactosylation and 30% in sialylation 976:1045 Variation of dissolved oxygen tension (10-90% air saturation) resulted in a maximum variability of 20% in galactosylation and 30% in sialylation. 25173615 3 67 theme stress 478:483 arg1 parameters 485:494 single and combined chemical and mechanical stress parameters 434:494 single and combined chemical and mechanical stress parameters 434:494 In this study we investigated the effect of single and combined chemical and mechanical stress parameters on the glycan microheterogeneity of an IgG1 antibody using a shift-experiment procedure in batch cultures. 25173615 5 68 from sialylation 854:864 arg1 range 799:803 a pH range 794:803 a pH range of 6.8 to 7.8 differences in galactosylation and sialylation of approximately 50% 794:885 Within a pH range of 6.8 to 7.8 differences in galactosylation and sialylation of approximately 50% were obtained. 25173615 1 69 gly glycosylation 150:162 arg1 antibodies 199:208 the produced monoclonal antibodies 175:208 the produced monoclonal antibodies 175:208 Bioreactor process parameters influence the N-linked glycosylation profile of the produced monoclonal antibodies. 25173615 1 70 theme process 108:114 arg1 parameters 116:125 Bioreactor process parameters 97:125 Bioreactor process parameters 97:125 Bioreactor process parameters influence the N-linked glycosylation profile of the produced monoclonal antibodies. 25173615 4 71 theme glycosylation 616:628 arg1 complex 680:686 complex 680:686 complex 680:686 The N-linked glycosylation profile of the murine IgG1 was found to be highly complex since it included terminal galactosylation and sialylation, as well as variable core-fucosylation. 25173615 4 71 theme glycosylation 616:628 arg1 profile 630:636 The N-linked glycosylation profile 603:636 The N-linked glycosylation profile of the murine IgG1 603:655 The N-linked glycosylation profile of the murine IgG1 was found to be highly complex since it included terminal galactosylation and sialylation, as well as variable core-fucosylation. 25173615 6 72 from variability 986:996 arg1 sialylation 1035:1045 sialylation 1035:1045 sialylation 1035:1045 Variation of dissolved oxygen tension (10-90% air saturation) resulted in a maximum variability of 20% in galactosylation and 30% in sialylation. 25173615 6 72 from variability 986:996 arg1 galactosylation 1008:1022 galactosylation 1008:1022 galactosylation 1008:1022 Variation of dissolved oxygen tension (10-90% air saturation) resulted in a maximum variability of 20% in galactosylation and 30% in sialylation. 25173615 8 73 theme closer 1376:1381 arg1 step 1371:1374 one step 1367:1374 us one step closer towards desired and targeted glycosylation for future therapeutic proteins 1364:1456 In this study a better understanding of bioprocess-related factors affecting critical quality attributes under the scope of QbD is provided and can bring us one step closer towards desired and targeted glycosylation for future therapeutic proteins. 25173615 3 74 theme glycan 503:508 arg1 microheterogeneity 510:527 the glycan microheterogeneity 499:527 the glycan microheterogeneity of an IgG1 antibody 499:547 In this study we investigated the effect of single and combined chemical and mechanical stress parameters on the glycan microheterogeneity of an IgG1 antibody using a shift-experiment procedure in batch cultures. 25173615 0 75 theme culture 30:36 arg1 parameters 46:55 cell culture process parameters 25:55 cell culture process parameters 25:55 Evaluating the impact of cell culture process parameters on monoclonal antibody N-glycosylation. 25173615 3 76 theme combined 445:452 arg1 parameters 485:494 single and combined chemical and mechanical stress parameters 434:494 single and combined chemical and mechanical stress parameters 434:494 In this study we investigated the effect of single and combined chemical and mechanical stress parameters on the glycan microheterogeneity of an IgG1 antibody using a shift-experiment procedure in batch cultures. 25173615 8 77 theme desired 1391:1397 arg1 glycosylation 1412:1424 desired and targeted glycosylation 1391:1424 desired and targeted glycosylation for future therapeutic proteins 1391:1456 In this study a better understanding of bioprocess-related factors affecting critical quality attributes under the scope of QbD is provided and can bring us one step closer towards desired and targeted glycosylation for future therapeutic proteins. 25173615 0 78 theme parameters 46:55 arg1 impact 15:20 the impact 11:20 the impact of cell culture process parameters on monoclonal antibody N-glycosylation 11:94 Evaluating the impact of cell culture process parameters on monoclonal antibody N-glycosylation. 25173615 3 79 theme single 434:439 arg1 parameters 485:494 single and combined chemical and mechanical stress parameters 434:494 single and combined chemical and mechanical stress parameters 434:494 In this study we investigated the effect of single and combined chemical and mechanical stress parameters on the glycan microheterogeneity of an IgG1 antibody using a shift-experiment procedure in batch cultures. 25173615 7 80 dep 0.2 1201:1203 arg1 to 1198:1199 to 1198:1199 to 1198:1199 In contrast, no significant effect on the glycosylation profile was observed when osmolarity increased from 320 to 420 mOsm/kg and sparging from 0.05 to 0.2 vvm. 25173615 8 81 theme targeted 1403:1410 arg1 glycosylation 1412:1424 desired and targeted glycosylation 1391:1424 desired and targeted glycosylation for future therapeutic proteins 1391:1456 In this study a better understanding of bioprocess-related factors affecting critical quality attributes under the scope of QbD is provided and can bring us one step closer towards desired and targeted glycosylation for future therapeutic proteins. 25173615 3 82 theme IgG1 535:538 arg1 antibody 540:547 an IgG1 antibody 532:547 an IgG1 antibody 532:547 In this study we investigated the effect of single and combined chemical and mechanical stress parameters on the glycan microheterogeneity of an IgG1 antibody using a shift-experiment procedure in batch cultures. 25173615 2 83 theme attributes 352:361 arg1 one 319:321 one 319:321 one 319:321 A systematic assessment of their impact is a prerequisite for providing controllability over glycosylation, one of the most critical quality attributes of therapeutic antibodies. 25173615 2 83 theme attributes 352:361 arg1 attributes 352:361 the most critical quality attributes 326:361 the most critical quality attributes of therapeutic antibodies 326:387 A systematic assessment of their impact is a prerequisite for providing controllability over glycosylation, one of the most critical quality attributes of therapeutic antibodies. 25173615 2 83 theme attributes 352:361 arg1 glycosylation 304:316 glycosylation 304:316 glycosylation 304:316 A systematic assessment of their impact is a prerequisite for providing controllability over glycosylation, one of the most critical quality attributes of therapeutic antibodies. 25173615 8 84 theme therapeutic 1437:1447 arg1 proteins 1449:1456 future therapeutic proteins 1430:1456 future therapeutic proteins 1430:1456 In this study a better understanding of bioprocess-related factors affecting critical quality attributes under the scope of QbD is provided and can bring us one step closer towards desired and targeted glycosylation for future therapeutic proteins. 25173615 3 85 theme shift-experiment 557:572 arg1 procedure 574:582 a shift-experiment procedure 555:582 a shift-experiment procedure in batch cultures 555:600 In this study we investigated the effect of single and combined chemical and mechanical stress parameters on the glycan microheterogeneity of an IgG1 antibody using a shift-experiment procedure in batch cultures. 26259768 3 0 contain possess 526:532 arg1 strains 518:524 several strains 510:524 several strains 510:524 These species were once considered to be asaccharolytic, but it was recently shown that several strains possess a pathway for fucose uptake and metabolism, providing those isolates with a competitive advantage in vivo. 26259768 3 0 contain possess 526:532 arg2 pathway 536:542 a pathway 534:542 a pathway for fucose uptake and metabolism 534:575 These species were once considered to be asaccharolytic, but it was recently shown that several strains possess a pathway for fucose uptake and metabolism, providing those isolates with a competitive advantage in vivo. 26259768 7 1 theme campylobacters 1261:1274 arg1 arsenal 1250:1256 the metabolic arsenal 1236:1256 the metabolic arsenal of campylobacters 1236:1274 In addition, Vorwerk et al. add to the metabolic arsenal of campylobacters further highlighting the nutritional diversity among strains, even within the same species. 26259768 7 2 theme metabolic 1240:1248 arg1 arsenal 1250:1256 the metabolic arsenal 1236:1256 the metabolic arsenal of campylobacters 1236:1274 In addition, Vorwerk et al. add to the metabolic arsenal of campylobacters further highlighting the nutritional diversity among strains, even within the same species. 26259768 6 3 theme labeled 1112:1118 arg1 sugars 1120:1125 metabolically labeled sugars 1098:1125 metabolically labeled sugars 1098:1125 This discovery now provides researchers with the opportunity to introduce metabolically labeled sugars into campylobacters to study glycoconjugate biosynthesis within the cell. 26259768 4 4 theme catabolism 778:787 arg1 capable 759:765 capable 759:765 capable 759:765 Vorwerk et al. have now demonstrated through isotopologue profiling that certain strains of C. coli and C. jejuni are capable of glucose catabolism through the Entner-Doudoroff and pentose phosphate pathways. 26259768 1 5 theme worldwide 114:122 arg1 cause 78:82 a leading cause 68:82 a leading cause of gastrointestinal morbidity worldwide 68:122 Campylobacters are a leading cause of gastrointestinal morbidity worldwide and the majority of human infections are triggered by eating foods contaminated with Campylobacter jejuni or Campylobacter coli. 26259768 1 5 theme worldwide 114:122 arg1 Campylobacters 49:62 Campylobacters 49:62 Campylobacters 49:62 Campylobacters are a leading cause of gastrointestinal morbidity worldwide and the majority of human infections are triggered by eating foods contaminated with Campylobacter jejuni or Campylobacter coli. 26259768 7 6 dep Vorwerk 1214:1220 arg1 al. 1225:1227 Vorwerk et al. 1214:1227 Vorwerk et al. 1214:1227 In addition, Vorwerk et al. add to the metabolic arsenal of campylobacters further highlighting the nutritional diversity among strains, even within the same species. 26259768 4 7 theme glucose 770:776 arg1 catabolism 778:787 glucose catabolism 770:787 glucose catabolism through the Entner-Doudoroff and pentose phosphate pathways 770:847 Vorwerk et al. have now demonstrated through isotopologue profiling that certain strains of C. coli and C. jejuni are capable of glucose catabolism through the Entner-Doudoroff and pentose phosphate pathways. 26259768 4 8 theme jejuni 748:753 arg1 strains 722:728 certain strains 714:728 certain strains of C. coli and C. jejuni 714:753 Vorwerk et al. have now demonstrated through isotopologue profiling that certain strains of C. coli and C. jejuni are capable of glucose catabolism through the Entner-Doudoroff and pentose phosphate pathways. 26259768 1 9 theme leading 70:76 arg1 cause 78:82 a leading cause 68:82 a leading cause of gastrointestinal morbidity worldwide 68:122 Campylobacters are a leading cause of gastrointestinal morbidity worldwide and the majority of human infections are triggered by eating foods contaminated with Campylobacter jejuni or Campylobacter coli. 26259768 1 9 theme leading 70:76 arg1 Campylobacters 49:62 Campylobacters 49:62 Campylobacters 49:62 Campylobacters are a leading cause of gastrointestinal morbidity worldwide and the majority of human infections are triggered by eating foods contaminated with Campylobacter jejuni or Campylobacter coli. 26259768 5 10 theme fucose 878:883 arg1 fate 870:873 the fate 866:873 the fate of fucose that has only been shown to be used for nutrition 866:933 However, unlike the fate of fucose that has only been shown to be used for nutrition, glucose can be metabolized or incorporated into select amino acids and glycoconjugates. 26259768 5 11 theme select 984:989 arg1 acids 997:1001 select amino acids 984:1001 select amino acids 984:1001 However, unlike the fate of fucose that has only been shown to be used for nutrition, glucose can be metabolized or incorporated into select amino acids and glycoconjugates. 26259768 7 12 theme same 1354:1357 arg1 species 1359:1365 the same species 1350:1365 the same species 1350:1365 In addition, Vorwerk et al. add to the metabolic arsenal of campylobacters further highlighting the nutritional diversity among strains, even within the same species. 26259768 2 13 gly glycoproteins 407:419 arg1 glycoproteins 407:419 O-linked glycoproteins 398:419 O-linked glycoproteins 398:419 Campylobacters are equally notorious for their ability to mimic human glycoconjugate structures and for their capacity to synthesize both N- and O-linked glycoproteins. 26259768 1 14 theme gastrointestinal 87:102 arg1 worldwide 114:122 gastrointestinal morbidity worldwide 87:122 gastrointestinal morbidity worldwide 87:122 Campylobacters are a leading cause of gastrointestinal morbidity worldwide and the majority of human infections are triggered by eating foods contaminated with Campylobacter jejuni or Campylobacter coli. 26259768 4 15 theme isotopologue 686:697 arg1 profiling 699:707 isotopologue profiling 686:707 isotopologue profiling 686:707 Vorwerk et al. have now demonstrated through isotopologue profiling that certain strains of C. coli and C. jejuni are capable of glucose catabolism through the Entner-Doudoroff and pentose phosphate pathways. 26259768 0 16 theme capable 23:29 arg1 campylobacters 4:17 campylobacters 4:17 campylobacters now capable of carbo-loading 4:46 Are campylobacters now capable of carbo-loading? 26259768 4 17 theme phosphate 830:838 arg1 pathways 840:847 the Entner-Doudoroff and pentose phosphate pathways 797:847 the Entner-Doudoroff and pentose phosphate pathways 797:847 Vorwerk et al. have now demonstrated through isotopologue profiling that certain strains of C. coli and C. jejuni are capable of glucose catabolism through the Entner-Doudoroff and pentose phosphate pathways. 26259768 2 18 theme glycoconjugate 323:336 arg1 structures 338:347 human glycoconjugate structures 317:347 human glycoconjugate structures 317:347 Campylobacters are equally notorious for their ability to mimic human glycoconjugate structures and for their capacity to synthesize both N- and O-linked glycoproteins. 26259768 3 19 dep in 632:633 arg1 vivo 635:638 vivo 635:638 vivo 635:638 These species were once considered to be asaccharolytic, but it was recently shown that several strains possess a pathway for fucose uptake and metabolism, providing those isolates with a competitive advantage in vivo. 26259768 3 20 with isolates 594:601 arg1 advantage 622:630 a competitive advantage 608:630 a competitive advantage in vivo 608:638 These species were once considered to be asaccharolytic, but it was recently shown that several strains possess a pathway for fucose uptake and metabolism, providing those isolates with a competitive advantage in vivo. 26259768 3 21 theme fucose 548:553 arg1 uptake 555:560 fucose uptake 548:560 fucose uptake 548:560 These species were once considered to be asaccharolytic, but it was recently shown that several strains possess a pathway for fucose uptake and metabolism, providing those isolates with a competitive advantage in vivo. 26259768 2 22 theme human 317:321 arg1 structures 338:347 human glycoconjugate structures 317:347 human glycoconjugate structures 317:347 Campylobacters are equally notorious for their ability to mimic human glycoconjugate structures and for their capacity to synthesize both N- and O-linked glycoproteins. 26259768 4 23 theme certain 714:720 arg1 strains 722:728 certain strains 714:728 certain strains of C. coli and C. jejuni 714:753 Vorwerk et al. have now demonstrated through isotopologue profiling that certain strains of C. coli and C. jejuni are capable of glucose catabolism through the Entner-Doudoroff and pentose phosphate pathways. 26259768 0 24 theme carbo-loading 34:46 arg1 capable 23:29 capable 23:29 capable 23:29 Are campylobacters now capable of carbo-loading? 26259768 2 25 link O-linked 398:405 arg1 glycoproteins 407:419 O-linked glycoproteins 398:419 O-linked glycoproteins 398:419 Campylobacters are equally notorious for their ability to mimic human glycoconjugate structures and for their capacity to synthesize both N- and O-linked glycoproteins. 26259768 3 26 theme competitive 610:620 arg1 advantage 622:630 a competitive advantage 608:630 a competitive advantage in vivo 608:638 These species were once considered to be asaccharolytic, but it was recently shown that several strains possess a pathway for fucose uptake and metabolism, providing those isolates with a competitive advantage in vivo. 26259768 2 27 theme O-linked 398:405 arg1 glycoproteins 407:419 O-linked glycoproteins 398:419 O-linked glycoproteins 398:419 Campylobacters are equally notorious for their ability to mimic human glycoconjugate structures and for their capacity to synthesize both N- and O-linked glycoproteins. 26259768 1 28 dep Campylobacter 233:245 arg1 coli 247:250 Campylobacter coli 233:250 Campylobacter coli 233:250 Campylobacters are a leading cause of gastrointestinal morbidity worldwide and the majority of human infections are triggered by eating foods contaminated with Campylobacter jejuni or Campylobacter coli. 26259768 3 29 theme several 510:516 arg1 strains 518:524 several strains 510:524 several strains 510:524 These species were once considered to be asaccharolytic, but it was recently shown that several strains possess a pathway for fucose uptake and metabolism, providing those isolates with a competitive advantage in vivo. 26259768 6 30 with researchers 1052:1062 arg1 opportunity 1073:1083 the opportunity to introduce metabolically labeled sugars into campylobacters 1069:1145 the opportunity to introduce metabolically labeled sugars into campylobacters 1069:1145 This discovery now provides researchers with the opportunity to introduce metabolically labeled sugars into campylobacters to study glycoconjugate biosynthesis within the cell. 26259768 4 31 dep Vorwerk 641:647 arg1 al. 652:654 Vorwerk et al. 641:654 Vorwerk et al. 641:654 Vorwerk et al. have now demonstrated through isotopologue profiling that certain strains of C. coli and C. jejuni are capable of glucose catabolism through the Entner-Doudoroff and pentose phosphate pathways. 26259768 6 32 theme glycoconjugate 1156:1169 arg1 biosynthesis 1171:1182 glycoconjugate biosynthesis 1156:1182 glycoconjugate biosynthesis 1156:1182 This discovery now provides researchers with the opportunity to introduce metabolically labeled sugars into campylobacters to study glycoconjugate biosynthesis within the cell. 26259768 5 33 used used 916:919 arg2 fate 870:873 the fate 866:873 the fate of fucose that has only been shown to be used for nutrition 866:933 However, unlike the fate of fucose that has only been shown to be used for nutrition, glucose can be metabolized or incorporated into select amino acids and glycoconjugates. 26259768 4 34 theme coli 736:739 arg1 strains 722:728 certain strains 714:728 certain strains of C. coli and C. jejuni 714:753 Vorwerk et al. have now demonstrated through isotopologue profiling that certain strains of C. coli and C. jejuni are capable of glucose catabolism through the Entner-Doudoroff and pentose phosphate pathways. 26259768 5 35 theme amino 991:995 arg1 acids 997:1001 select amino acids 984:1001 select amino acids 984:1001 However, unlike the fate of fucose that has only been shown to be used for nutrition, glucose can be metabolized or incorporated into select amino acids and glycoconjugates. 26259768 4 36 theme C. 745:746 arg1 jejuni 748:753 C. jejuni 745:753 C. jejuni 745:753 Vorwerk et al. have now demonstrated through isotopologue profiling that certain strains of C. coli and C. jejuni are capable of glucose catabolism through the Entner-Doudoroff and pentose phosphate pathways. 26259768 1 37 theme morbidity 104:112 arg1 worldwide 114:122 gastrointestinal morbidity worldwide 87:122 gastrointestinal morbidity worldwide 87:122 Campylobacters are a leading cause of gastrointestinal morbidity worldwide and the majority of human infections are triggered by eating foods contaminated with Campylobacter jejuni or Campylobacter coli. 26259768 4 38 theme Entner-Doudoroff 801:816 arg1 pathways 840:847 the Entner-Doudoroff and pentose phosphate pathways 797:847 the Entner-Doudoroff and pentose phosphate pathways 797:847 Vorwerk et al. have now demonstrated through isotopologue profiling that certain strains of C. coli and C. jejuni are capable of glucose catabolism through the Entner-Doudoroff and pentose phosphate pathways. 26259768 7 39 theme nutritional 1301:1311 arg1 diversity 1313:1321 the nutritional diversity 1297:1321 the nutritional diversity among strains, even within the same species 1297:1365 In addition, Vorwerk et al. add to the metabolic arsenal of campylobacters further highlighting the nutritional diversity among strains, even within the same species. 26259768 3 40 theme in 632:633 arg1 advantage 622:630 a competitive advantage 608:630 a competitive advantage in vivo 608:638 These species were once considered to be asaccharolytic, but it was recently shown that several strains possess a pathway for fucose uptake and metabolism, providing those isolates with a competitive advantage in vivo. 26259768 1 41 theme human 144:148 arg1 infections 150:159 human infections 144:159 human infections 144:159 Campylobacters are a leading cause of gastrointestinal morbidity worldwide and the majority of human infections are triggered by eating foods contaminated with Campylobacter jejuni or Campylobacter coli. 26259768 4 42 theme pentose 822:828 arg1 pathways 840:847 the Entner-Doudoroff and pentose phosphate pathways 797:847 the Entner-Doudoroff and pentose phosphate pathways 797:847 Vorwerk et al. have now demonstrated through isotopologue profiling that certain strains of C. coli and C. jejuni are capable of glucose catabolism through the Entner-Doudoroff and pentose phosphate pathways. 26259768 1 43 theme infections 150:159 arg1 majority 132:139 the majority 128:139 the majority of human infections 128:159 Campylobacters are a leading cause of gastrointestinal morbidity worldwide and the majority of human infections are triggered by eating foods contaminated with Campylobacter jejuni or Campylobacter coli. 25751766 5 0 theme mammalian 743:751 arg1 lines 758:762 several mammalian cell lines 735:762 several mammalian cell lines 735:762 It is cell-permeable and inhibits protein O-GlcNAcylation in several mammalian cell lines without qualitatively altering cell surface N- or O-linked glycans. 25751766 4 1 theme high-throughput 643:657 arg1 hit 669:671 a high-throughput screening hit 641:671 a high-throughput screening hit 641:671 Here, we report a small molecule OGT inhibitor, OSMI-1, developed from a high-throughput screening hit. 25751766 6 2 dep potent 1028:1033 arg1 OGT 1035:1037 OGT 1035:1037 OGT 1035:1037 The development of this molecule validates high-throughput screening approaches for the discovery of glycosyltransferase inhibitors, and further optimization of this scaffold may lead to yet more potent OGT inhibitors useful for studying OGT in animal models. 25751766 1 3 theme numerous 129:136 arg1 processes 147:155 numerous cellular processes 129:155 numerous cellular processes 129:155 O-GlcNAc transferase (OGT) is an essential mammalian enzyme that regulates numerous cellular processes through the attachment of O-linked N-acetylglucosamine (O-GlcNAc) residues to nuclear and cytoplasmic proteins. 25751766 1 4 theme nuclear 235:241 arg1 proteins 259:266 nuclear and cytoplasmic proteins 235:266 nuclear and cytoplasmic proteins 235:266 O-GlcNAc transferase (OGT) is an essential mammalian enzyme that regulates numerous cellular processes through the attachment of O-linked N-acetylglucosamine (O-GlcNAc) residues to nuclear and cytoplasmic proteins. 25751766 5 5 theme cell 753:756 arg1 lines 758:762 several mammalian cell lines 735:762 several mammalian cell lines 735:762 It is cell-permeable and inhibits protein O-GlcNAcylation in several mammalian cell lines without qualitatively altering cell surface N- or O-linked glycans. 25751766 1 6 theme cellular 138:145 arg1 processes 147:155 numerous cellular processes 129:155 numerous cellular processes 129:155 O-GlcNAc transferase (OGT) is an essential mammalian enzyme that regulates numerous cellular processes through the attachment of O-linked N-acetylglucosamine (O-GlcNAc) residues to nuclear and cytoplasmic proteins. 25751766 5 7 link O-linked 814:821 arg1 glycans 823:829 O-linked glycans 814:829 O-linked glycans 814:829 It is cell-permeable and inhibits protein O-GlcNAcylation in several mammalian cell lines without qualitatively altering cell surface N- or O-linked glycans. 25751766 6 8 from OGT 1070:1072 arg1 models 1084:1089 animal models 1077:1089 animal models 1077:1089 The development of this molecule validates high-throughput screening approaches for the discovery of glycosyltransferase inhibitors, and further optimization of this scaffold may lead to yet more potent OGT inhibitors useful for studying OGT in animal models. 25751766 1 9 theme cytoplasmic 247:257 arg1 proteins 259:266 nuclear and cytoplasmic proteins 235:266 nuclear and cytoplasmic proteins 235:266 O-GlcNAc transferase (OGT) is an essential mammalian enzyme that regulates numerous cellular processes through the attachment of O-linked N-acetylglucosamine (O-GlcNAc) residues to nuclear and cytoplasmic proteins. 25751766 4 10 theme molecule 594:601 arg1 inhibitor 607:615 a small molecule OGT inhibitor 586:615 a small molecule OGT inhibitor 586:615 Here, we report a small molecule OGT inhibitor, OSMI-1, developed from a high-throughput screening hit. 25751766 4 10 theme molecule 594:601 arg1 OSMI-1 618:623 OSMI-1 618:623 OSMI-1 618:623 Here, we report a small molecule OGT inhibitor, OSMI-1, developed from a high-throughput screening hit. 25751766 1 11 link O-linked 183:190 arg1 O-GlcNAc 213:220 O-GlcNAc 213:220 O-GlcNAc 213:220 O-GlcNAc transferase (OGT) is an essential mammalian enzyme that regulates numerous cellular processes through the attachment of O-linked N-acetylglucosamine (O-GlcNAc) residues to nuclear and cytoplasmic proteins. 25751766 1 11 link O-linked 183:190 arg1 N-acetylglucosamine 192:210 O-linked N-acetylglucosamine 183:210 O-linked N-acetylglucosamine (O-GlcNAc) residues 183:230 O-GlcNAc transferase (OGT) is an essential mammalian enzyme that regulates numerous cellular processes through the attachment of O-linked N-acetylglucosamine (O-GlcNAc) residues to nuclear and cytoplasmic proteins. 25751766 6 12 theme scaffold 998:1005 arg1 optimization 977:988 further optimization 969:988 further optimization of this scaffold 969:1005 The development of this molecule validates high-throughput screening approaches for the discovery of glycosyltransferase inhibitors, and further optimization of this scaffold may lead to yet more potent OGT inhibitors useful for studying OGT in animal models. 25751766 5 13 theme protein 708:714 arg1 O-GlcNAcylation 716:730 protein O-GlcNAcylation 708:730 protein O-GlcNAcylation 708:730 It is cell-permeable and inhibits protein O-GlcNAcylation in several mammalian cell lines without qualitatively altering cell surface N- or O-linked glycans. 25751766 0 14 from activity 35:42 arg1 cells 47:51 cells 47:51 cells 47:51 A small molecule that inhibits OGT activity in cells. 25751766 3 15 theme cell-permeable 455:468 arg1 inhibitors 470:479 cell-permeable inhibitors 455:479 cell-permeable inhibitors of OGT 455:486 The biology of O-GlcNAc modification is still not well understood, and cell-permeable inhibitors of OGT are needed both as research tools and for validating OGT as a therapeutic target. 25751766 3 15 theme cell-permeable 455:468 arg1 validating 530:539 validating 530:539 validating OGT as a therapeutic target 530:567 The biology of O-GlcNAc modification is still not well understood, and cell-permeable inhibitors of OGT are needed both as research tools and for validating OGT as a therapeutic target. 25751766 3 15 theme cell-permeable 455:468 arg1 tools 516:520 research tools 507:520 research tools 507:520 The biology of O-GlcNAc modification is still not well understood, and cell-permeable inhibitors of OGT are needed both as research tools and for validating OGT as a therapeutic target. 25751766 1 16 theme O-GlcNAc 54:61 arg1 OGT 76:78 OGT 76:78 OGT 76:78 O-GlcNAc transferase (OGT) is an essential mammalian enzyme that regulates numerous cellular processes through the attachment of O-linked N-acetylglucosamine (O-GlcNAc) residues to nuclear and cytoplasmic proteins. 25751766 1 16 theme O-GlcNAc 54:61 arg1 transferase 63:73 O-GlcNAc transferase 54:73 O-GlcNAc transferase (OGT) 54:79 O-GlcNAc transferase (OGT) is an essential mammalian enzyme that regulates numerous cellular processes through the attachment of O-linked N-acetylglucosamine (O-GlcNAc) residues to nuclear and cytoplasmic proteins. 25751766 1 16 theme O-GlcNAc 54:61 arg1 enzyme 107:112 an essential mammalian enzyme 84:112 an essential mammalian enzyme that regulates numerous cellular processes through the attachment of O-linked N-acetylglucosamine (O-GlcNAc) residues to nuclear and cytoplasmic proteins 84:266 O-GlcNAc transferase (OGT) is an essential mammalian enzyme that regulates numerous cellular processes through the attachment of O-linked N-acetylglucosamine (O-GlcNAc) residues to nuclear and cytoplasmic proteins. 25751766 6 17 theme high-throughput 875:889 arg1 approaches 901:910 high-throughput screening approaches 875:910 high-throughput screening approaches for the discovery of glycosyltransferase inhibitors 875:962 The development of this molecule validates high-throughput screening approaches for the discovery of glycosyltransferase inhibitors, and further optimization of this scaffold may lead to yet more potent OGT inhibitors useful for studying OGT in animal models. 25751766 3 18 theme O-GlcNAc 399:406 arg1 modification 408:419 O-GlcNAc modification 399:419 O-GlcNAc modification 399:419 The biology of O-GlcNAc modification is still not well understood, and cell-permeable inhibitors of OGT are needed both as research tools and for validating OGT as a therapeutic target. 25751766 6 19 theme animal 1077:1082 arg1 models 1084:1089 animal models 1077:1089 animal models 1077:1089 The development of this molecule validates high-throughput screening approaches for the discovery of glycosyltransferase inhibitors, and further optimization of this scaffold may lead to yet more potent OGT inhibitors useful for studying OGT in animal models. 25751766 0 20 theme small 2:6 arg1 molecule 8:15 A small molecule 0:15 A small molecule that inhibits OGT activity in cells 0:51 A small molecule that inhibits OGT activity in cells. 25751766 3 21 theme research 507:514 arg1 tools 516:520 research tools 507:520 research tools 507:520 The biology of O-GlcNAc modification is still not well understood, and cell-permeable inhibitors of OGT are needed both as research tools and for validating OGT as a therapeutic target. 25751766 3 21 theme research 507:514 arg1 inhibitors 470:479 cell-permeable inhibitors 455:479 cell-permeable inhibitors of OGT 455:486 The biology of O-GlcNAc modification is still not well understood, and cell-permeable inhibitors of OGT are needed both as research tools and for validating OGT as a therapeutic target. 25751766 6 22 theme screening 891:899 arg1 approaches 901:910 high-throughput screening approaches 875:910 high-throughput screening approaches for the discovery of glycosyltransferase inhibitors 875:962 The development of this molecule validates high-throughput screening approaches for the discovery of glycosyltransferase inhibitors, and further optimization of this scaffold may lead to yet more potent OGT inhibitors useful for studying OGT in animal models. 25751766 3 23 theme therapeutic 550:560 arg1 target 562:567 a therapeutic target 548:567 a therapeutic target 548:567 The biology of O-GlcNAc modification is still not well understood, and cell-permeable inhibitors of OGT are needed both as research tools and for validating OGT as a therapeutic target. 25751766 3 23 theme therapeutic 550:560 arg1 OGT 541:543 OGT 541:543 OGT 541:543 The biology of O-GlcNAc modification is still not well understood, and cell-permeable inhibitors of OGT are needed both as research tools and for validating OGT as a therapeutic target. 25751766 2 24 theme intracellular 360:372 arg1 proteins 374:381 many other intracellular proteins 349:381 many other intracellular proteins 349:381 Its targets include kinases, phosphatases, transcription factors, histones, and many other intracellular proteins. 25751766 4 25 theme OGT 603:605 arg1 inhibitor 607:615 a small molecule OGT inhibitor 586:615 a small molecule OGT inhibitor 586:615 Here, we report a small molecule OGT inhibitor, OSMI-1, developed from a high-throughput screening hit. 25751766 4 25 theme OGT 603:605 arg1 OSMI-1 618:623 OSMI-1 618:623 OSMI-1 618:623 Here, we report a small molecule OGT inhibitor, OSMI-1, developed from a high-throughput screening hit. 25751766 6 26 theme molecule 856:863 arg1 development 836:846 The development 832:846 The development of this molecule 832:863 The development of this molecule validates high-throughput screening approaches for the discovery of glycosyltransferase inhibitors, and further optimization of this scaffold may lead to yet more potent OGT inhibitors useful for studying OGT in animal models. 25751766 4 27 theme screening 659:667 arg1 hit 669:671 a high-throughput screening hit 641:671 a high-throughput screening hit 641:671 Here, we report a small molecule OGT inhibitor, OSMI-1, developed from a high-throughput screening hit. 25751766 1 28 theme O-linked 183:190 arg1 O-GlcNAc 213:220 O-GlcNAc 213:220 O-GlcNAc 213:220 O-GlcNAc transferase (OGT) is an essential mammalian enzyme that regulates numerous cellular processes through the attachment of O-linked N-acetylglucosamine (O-GlcNAc) residues to nuclear and cytoplasmic proteins. 25751766 1 28 theme O-linked 183:190 arg1 N-acetylglucosamine 192:210 O-linked N-acetylglucosamine 183:210 O-linked N-acetylglucosamine (O-GlcNAc) residues 183:230 O-GlcNAc transferase (OGT) is an essential mammalian enzyme that regulates numerous cellular processes through the attachment of O-linked N-acetylglucosamine (O-GlcNAc) residues to nuclear and cytoplasmic proteins. 25751766 0 29 theme OGT 31:33 arg1 activity 35:42 OGT activity 31:42 OGT activity in cells 31:51 A small molecule that inhibits OGT activity in cells. 25751766 6 30 theme further 969:975 arg1 optimization 977:988 further optimization 969:988 further optimization of this scaffold 969:1005 The development of this molecule validates high-throughput screening approaches for the discovery of glycosyltransferase inhibitors, and further optimization of this scaffold may lead to yet more potent OGT inhibitors useful for studying OGT in animal models. 25751766 6 31 theme useful 1050:1055 arg1 inhibitors 1039:1048 yet more potent OGT inhibitors 1019:1048 yet more potent OGT inhibitors useful for studying OGT in animal models 1019:1089 The development of this molecule validates high-throughput screening approaches for the discovery of glycosyltransferase inhibitors, and further optimization of this scaffold may lead to yet more potent OGT inhibitors useful for studying OGT in animal models. 25751766 1 32 theme N-acetylglucosamine 192:210 arg1 residues 223:230 O-linked N-acetylglucosamine (O-GlcNAc) residues 183:230 O-linked N-acetylglucosamine (O-GlcNAc) residues 183:230 O-GlcNAc transferase (OGT) is an essential mammalian enzyme that regulates numerous cellular processes through the attachment of O-linked N-acetylglucosamine (O-GlcNAc) residues to nuclear and cytoplasmic proteins. 25751766 3 33 theme modification 408:419 arg1 biology 388:394 The biology 384:394 The biology of O-GlcNAc modification 384:419 The biology of O-GlcNAc modification is still not well understood, and cell-permeable inhibitors of OGT are needed both as research tools and for validating OGT as a therapeutic target. 25751766 1 34 attach attachment 169:178 arg2 residues 223:230 O-linked N-acetylglucosamine (O-GlcNAc) residues 183:230 O-linked N-acetylglucosamine (O-GlcNAc) residues 183:230 O-GlcNAc transferase (OGT) is an essential mammalian enzyme that regulates numerous cellular processes through the attachment of O-linked N-acetylglucosamine (O-GlcNAc) residues to nuclear and cytoplasmic proteins. 25751766 1 34 attach attachment 169:178 arg1 proteins 259:266 nuclear and cytoplasmic proteins 235:266 nuclear and cytoplasmic proteins 235:266 O-GlcNAc transferase (OGT) is an essential mammalian enzyme that regulates numerous cellular processes through the attachment of O-linked N-acetylglucosamine (O-GlcNAc) residues to nuclear and cytoplasmic proteins. 25751766 4 35 theme small 588:592 arg1 inhibitor 607:615 a small molecule OGT inhibitor 586:615 a small molecule OGT inhibitor 586:615 Here, we report a small molecule OGT inhibitor, OSMI-1, developed from a high-throughput screening hit. 25751766 4 35 theme small 588:592 arg1 OSMI-1 618:623 OSMI-1 618:623 OSMI-1 618:623 Here, we report a small molecule OGT inhibitor, OSMI-1, developed from a high-throughput screening hit. 25751766 3 36 theme OGT 484:486 arg1 inhibitors 470:479 cell-permeable inhibitors 455:479 cell-permeable inhibitors of OGT 455:486 The biology of O-GlcNAc modification is still not well understood, and cell-permeable inhibitors of OGT are needed both as research tools and for validating OGT as a therapeutic target. 25751766 3 36 theme OGT 484:486 arg1 validating 530:539 validating 530:539 validating OGT as a therapeutic target 530:567 The biology of O-GlcNAc modification is still not well understood, and cell-permeable inhibitors of OGT are needed both as research tools and for validating OGT as a therapeutic target. 25751766 3 36 theme OGT 484:486 arg1 tools 516:520 research tools 507:520 research tools 507:520 The biology of O-GlcNAc modification is still not well understood, and cell-permeable inhibitors of OGT are needed both as research tools and for validating OGT as a therapeutic target. 25751766 5 37 dep surface 800:806 arg1 N- 808:809 N- 808:809 N- 808:809 It is cell-permeable and inhibits protein O-GlcNAcylation in several mammalian cell lines without qualitatively altering cell surface N- or O-linked glycans. 25751766 5 37 dep surface 800:806 arg1 glycans 823:829 O-linked glycans 814:829 O-linked glycans 814:829 It is cell-permeable and inhibits protein O-GlcNAcylation in several mammalian cell lines without qualitatively altering cell surface N- or O-linked glycans. 25751766 6 38 theme inhibitors 953:962 arg1 discovery 920:928 the discovery 916:928 the discovery of glycosyltransferase inhibitors 916:962 The development of this molecule validates high-throughput screening approaches for the discovery of glycosyltransferase inhibitors, and further optimization of this scaffold may lead to yet more potent OGT inhibitors useful for studying OGT in animal models. 25751766 1 39 theme essential 87:95 arg1 enzyme 107:112 an essential mammalian enzyme 84:112 an essential mammalian enzyme that regulates numerous cellular processes through the attachment of O-linked N-acetylglucosamine (O-GlcNAc) residues to nuclear and cytoplasmic proteins 84:266 O-GlcNAc transferase (OGT) is an essential mammalian enzyme that regulates numerous cellular processes through the attachment of O-linked N-acetylglucosamine (O-GlcNAc) residues to nuclear and cytoplasmic proteins. 25751766 1 39 theme essential 87:95 arg1 transferase 63:73 O-GlcNAc transferase 54:73 O-GlcNAc transferase (OGT) 54:79 O-GlcNAc transferase (OGT) is an essential mammalian enzyme that regulates numerous cellular processes through the attachment of O-linked N-acetylglucosamine (O-GlcNAc) residues to nuclear and cytoplasmic proteins. 25751766 6 40 theme glycosyltransferase 933:951 arg1 inhibitors 953:962 glycosyltransferase inhibitors 933:962 glycosyltransferase inhibitors 933:962 The development of this molecule validates high-throughput screening approaches for the discovery of glycosyltransferase inhibitors, and further optimization of this scaffold may lead to yet more potent OGT inhibitors useful for studying OGT in animal models. 25751766 1 41 theme mammalian 97:105 arg1 enzyme 107:112 an essential mammalian enzyme 84:112 an essential mammalian enzyme that regulates numerous cellular processes through the attachment of O-linked N-acetylglucosamine (O-GlcNAc) residues to nuclear and cytoplasmic proteins 84:266 O-GlcNAc transferase (OGT) is an essential mammalian enzyme that regulates numerous cellular processes through the attachment of O-linked N-acetylglucosamine (O-GlcNAc) residues to nuclear and cytoplasmic proteins. 25751766 1 41 theme mammalian 97:105 arg1 transferase 63:73 O-GlcNAc transferase 54:73 O-GlcNAc transferase (OGT) 54:79 O-GlcNAc transferase (OGT) is an essential mammalian enzyme that regulates numerous cellular processes through the attachment of O-linked N-acetylglucosamine (O-GlcNAc) residues to nuclear and cytoplasmic proteins. 25751766 5 42 theme cell 795:798 arg1 surface 800:806 cell surface N- or O-linked glycans 795:829 cell surface N- or O-linked glycans 795:829 It is cell-permeable and inhibits protein O-GlcNAcylation in several mammalian cell lines without qualitatively altering cell surface N- or O-linked glycans. 25751766 2 43 theme transcription 312:324 arg1 factors 326:332 transcription factors 312:332 transcription factors 312:332 Its targets include kinases, phosphatases, transcription factors, histones, and many other intracellular proteins. 25751766 6 44 theme potent 1028:1033 arg1 inhibitors 1039:1048 yet more potent OGT inhibitors 1019:1048 yet more potent OGT inhibitors useful for studying OGT in animal models 1019:1089 The development of this molecule validates high-throughput screening approaches for the discovery of glycosyltransferase inhibitors, and further optimization of this scaffold may lead to yet more potent OGT inhibitors useful for studying OGT in animal models. 25751766 5 45 theme O-linked 814:821 arg1 glycans 823:829 O-linked glycans 814:829 O-linked glycans 814:829 It is cell-permeable and inhibits protein O-GlcNAcylation in several mammalian cell lines without qualitatively altering cell surface N- or O-linked glycans. 25751766 2 46 theme other 354:358 arg1 proteins 374:381 many other intracellular proteins 349:381 many other intracellular proteins 349:381 Its targets include kinases, phosphatases, transcription factors, histones, and many other intracellular proteins. 25751766 1 47 theme residues 223:230 arg1 attachment 169:178 the attachment 165:178 the attachment of O-linked N-acetylglucosamine (O-GlcNAc) residues to nuclear and cytoplasmic proteins 165:266 O-GlcNAc transferase (OGT) is an essential mammalian enzyme that regulates numerous cellular processes through the attachment of O-linked N-acetylglucosamine (O-GlcNAc) residues to nuclear and cytoplasmic proteins. 25751766 5 48 theme several 735:741 arg1 lines 758:762 several mammalian cell lines 735:762 several mammalian cell lines 735:762 It is cell-permeable and inhibits protein O-GlcNAcylation in several mammalian cell lines without qualitatively altering cell surface N- or O-linked glycans. 25751766 2 49 theme many 349:352 arg1 proteins 374:381 many other intracellular proteins 349:381 many other intracellular proteins 349:381 Its targets include kinases, phosphatases, transcription factors, histones, and many other intracellular proteins. 27655785 5 0 theme excessive 1143:1151 arg1 intake 1162:1167 excessive fructose intake 1143:1167 excessive fructose intake 1143:1167 These results reveal novel functional roles of fructose in promoting embryonic/fetal growth and development during pregnancy, and also provide new insight into understanding the relationship between excessive fructose intake and metabolic disorders. 27655785 4 1 theme primary 888:894 arg1 product 896:902 a primary product 886:902 a primary product of the hexosamine biosynthesis pathway 886:941 The phosphorylation for activation of this cascade is mediated by O-GlcNAcylation from UDP-N-acetylglucosamine (UDP-GlcNAc), a primary product of the hexosamine biosynthesis pathway. 27655785 4 1 theme primary 888:894 arg1 UDP-N-acetylglucosamine 848:870 UDP-N-acetylglucosamine 848:870 UDP-N-acetylglucosamine (UDP-GlcNAc) 848:883 The phosphorylation for activation of this cascade is mediated by O-GlcNAcylation from UDP-N-acetylglucosamine (UDP-GlcNAc), a primary product of the hexosamine biosynthesis pathway. 27655785 3 2 theme conceptus 674:682 arg1 trophectoderm/chorion 684:704 the conceptus trophectoderm/chorion 670:704 the conceptus trophectoderm/chorion 670:704 Here we provided evidence for biological functions of fructose that affect proliferative behavior of the conceptus trophectoderm/chorion via activation of the Akt-TSC2-MTOR signaling cascade. 27655785 2 3 from tissues 446:452 arg1 component 390:398 the most enigmatic component 371:398 the most enigmatic component of carbohydrate metabolism in fetal-placental tissues 371:452 However, the role of fructose, the most enigmatic component of carbohydrate metabolism in fetal-placental tissues, is largely ignored since it is not metabolized via the glycolytic pathway or the Krebs cycle as an energy source. 27655785 2 3 from tissues 446:452 arg1 fructose 361:368 fructose 361:368 fructose 361:368 However, the role of fructose, the most enigmatic component of carbohydrate metabolism in fetal-placental tissues, is largely ignored since it is not metabolized via the glycolytic pathway or the Krebs cycle as an energy source. 27655785 5 4 theme fructose 1153:1160 arg1 intake 1162:1167 excessive fructose intake 1143:1167 excessive fructose intake 1143:1167 These results reveal novel functional roles of fructose in promoting embryonic/fetal growth and development during pregnancy, and also provide new insight into understanding the relationship between excessive fructose intake and metabolic disorders. 27655785 2 5 from component 390:398 arg1 tissues 446:452 fetal-placental tissues 430:452 fetal-placental tissues 430:452 However, the role of fructose, the most enigmatic component of carbohydrate metabolism in fetal-placental tissues, is largely ignored since it is not metabolized via the glycolytic pathway or the Krebs cycle as an energy source. 27655785 0 6 theme Cell 108:111 arg1 Cascade 123:129 Akt-TSC2-MTOR Cell Signaling Cascade 94:129 Akt-TSC2-MTOR Cell Signaling Cascade 94:129 Functional Roles of Fructose: Crosstalk between O-Linked Glycosylation and Phosphorylation of Akt-TSC2-MTOR Cell Signaling Cascade in Ovine Trophectoderm Cells. 27655785 1 7 theme fetal 316:320 arg1 fluids 322:327 fetal fluids 316:327 fetal fluids 316:327 During pregnancy, the placentae of ungulate mammals (e.g., cows, sheep, and pigs) convert glucose into fructose which is the most abundant hexose sugar in fetal fluids and blood. 27655785 0 8 gly Glycosylation 57:69 arg1 Cascade 123:129 Akt-TSC2-MTOR Cell Signaling Cascade 94:129 Akt-TSC2-MTOR Cell Signaling Cascade 94:129 Functional Roles of Fructose: Crosstalk between O-Linked Glycosylation and Phosphorylation of Akt-TSC2-MTOR Cell Signaling Cascade in Ovine Trophectoderm Cells. 27655785 0 9 theme Akt-TSC2-MTOR 94:106 arg1 Cascade 123:129 Akt-TSC2-MTOR Cell Signaling Cascade 94:129 Akt-TSC2-MTOR Cell Signaling Cascade 94:129 Functional Roles of Fructose: Crosstalk between O-Linked Glycosylation and Phosphorylation of Akt-TSC2-MTOR Cell Signaling Cascade in Ovine Trophectoderm Cells. 27655785 2 10 from metabolism 416:425 arg1 tissues 446:452 fetal-placental tissues 430:452 fetal-placental tissues 430:452 However, the role of fructose, the most enigmatic component of carbohydrate metabolism in fetal-placental tissues, is largely ignored since it is not metabolized via the glycolytic pathway or the Krebs cycle as an energy source. 27655785 2 11 theme Krebs 536:540 arg1 cycle 542:546 the Krebs cycle 532:546 the Krebs cycle 532:546 However, the role of fructose, the most enigmatic component of carbohydrate metabolism in fetal-placental tissues, is largely ignored since it is not metabolized via the glycolytic pathway or the Krebs cycle as an energy source. 27655785 5 12 theme novel 965:969 arg1 roles 982:986 novel functional roles 965:986 novel functional roles of fructose in promoting embryonic/fetal growth and development during pregnancy 965:1067 These results reveal novel functional roles of fructose in promoting embryonic/fetal growth and development during pregnancy, and also provide new insight into understanding the relationship between excessive fructose intake and metabolic disorders. 27655785 0 13 theme Cascade 123:129 arg1 Phosphorylation 75:89 Phosphorylation 75:89 Phosphorylation 75:89 Functional Roles of Fructose: Crosstalk between O-Linked Glycosylation and Phosphorylation of Akt-TSC2-MTOR Cell Signaling Cascade in Ovine Trophectoderm Cells. 27655785 0 13 theme Cascade 123:129 arg1 Glycosylation 57:69 O-Linked Glycosylation 48:69 O-Linked Glycosylation 48:69 Functional Roles of Fructose: Crosstalk between O-Linked Glycosylation and Phosphorylation of Akt-TSC2-MTOR Cell Signaling Cascade in Ovine Trophectoderm Cells. 27655785 3 14 theme trophectoderm/chorion 684:704 arg1 behavior 658:665 proliferative behavior 644:665 proliferative behavior of the conceptus trophectoderm/chorion 644:704 Here we provided evidence for biological functions of fructose that affect proliferative behavior of the conceptus trophectoderm/chorion via activation of the Akt-TSC2-MTOR signaling cascade. 27655785 5 15 theme functional 971:980 arg1 roles 982:986 novel functional roles 965:986 novel functional roles of fructose in promoting embryonic/fetal growth and development during pregnancy 965:1067 These results reveal novel functional roles of fructose in promoting embryonic/fetal growth and development during pregnancy, and also provide new insight into understanding the relationship between excessive fructose intake and metabolic disorders. 27655785 0 16 theme Signaling 113:121 arg1 Cascade 123:129 Akt-TSC2-MTOR Cell Signaling Cascade 94:129 Akt-TSC2-MTOR Cell Signaling Cascade 94:129 Functional Roles of Fructose: Crosstalk between O-Linked Glycosylation and Phosphorylation of Akt-TSC2-MTOR Cell Signaling Cascade in Ovine Trophectoderm Cells. 27655785 0 17 theme Functional 0:9 arg1 Roles 11:15 Functional Roles 0:15 Functional Roles of Fructose: Crosstalk between O-Linked Glycosylation and Phosphorylation of Akt-TSC2-MTOR Cell Signaling Cascade in Ovine Trophectoderm Cells. 0:159 Functional Roles of Fructose: Crosstalk between O-Linked Glycosylation and Phosphorylation of Akt-TSC2-MTOR Cell Signaling Cascade in Ovine Trophectoderm Cells. 27655785 2 18 theme energy 554:559 arg1 source 561:566 an energy source 551:566 an energy source 551:566 However, the role of fructose, the most enigmatic component of carbohydrate metabolism in fetal-placental tissues, is largely ignored since it is not metabolized via the glycolytic pathway or the Krebs cycle as an energy source. 27655785 2 18 theme energy 554:559 arg1 it 480:481 it 480:481 it 480:481 However, the role of fructose, the most enigmatic component of carbohydrate metabolism in fetal-placental tissues, is largely ignored since it is not metabolized via the glycolytic pathway or the Krebs cycle as an energy source. 27655785 1 19 theme ungulate 196:203 arg1 mammals 205:211 ungulate mammals 196:211 ungulate mammals (e.g., cows, sheep, and pigs) 196:241 During pregnancy, the placentae of ungulate mammals (e.g., cows, sheep, and pigs) convert glucose into fructose which is the most abundant hexose sugar in fetal fluids and blood. 27655785 0 20 theme Fructose 20:27 arg1 Roles 11:15 Functional Roles 0:15 Functional Roles of Fructose: Crosstalk between O-Linked Glycosylation and Phosphorylation of Akt-TSC2-MTOR Cell Signaling Cascade in Ovine Trophectoderm Cells. 0:159 Functional Roles of Fructose: Crosstalk between O-Linked Glycosylation and Phosphorylation of Akt-TSC2-MTOR Cell Signaling Cascade in Ovine Trophectoderm Cells. 27655785 0 21 dep Roles 11:15 arg1 Crosstalk 30:38 Crosstalk 30:38 Functional Roles of Fructose: Crosstalk between O-Linked Glycosylation and Phosphorylation of Akt-TSC2-MTOR Cell Signaling Cascade in Ovine Trophectoderm Cells. 0:159 Functional Roles of Fructose: Crosstalk between O-Linked Glycosylation and Phosphorylation of Akt-TSC2-MTOR Cell Signaling Cascade in Ovine Trophectoderm Cells. 27655785 0 22 theme Ovine 134:138 arg1 Cells 154:158 Ovine Trophectoderm Cells 134:158 Ovine Trophectoderm Cells 134:158 Functional Roles of Fructose: Crosstalk between O-Linked Glycosylation and Phosphorylation of Akt-TSC2-MTOR Cell Signaling Cascade in Ovine Trophectoderm Cells. 27655785 1 23 theme mammals 205:211 arg1 placentae 183:191 the placentae 179:191 the placentae of ungulate mammals (e.g., cows, sheep, and pigs) 179:241 During pregnancy, the placentae of ungulate mammals (e.g., cows, sheep, and pigs) convert glucose into fructose which is the most abundant hexose sugar in fetal fluids and blood. 27655785 4 24 theme hexosamine 911:920 arg1 pathway 935:941 the hexosamine biosynthesis pathway 907:941 the hexosamine biosynthesis pathway 907:941 The phosphorylation for activation of this cascade is mediated by O-GlcNAcylation from UDP-N-acetylglucosamine (UDP-GlcNAc), a primary product of the hexosamine biosynthesis pathway. 27655785 2 25 theme fetal-placental 430:444 arg1 tissues 446:452 fetal-placental tissues 430:452 fetal-placental tissues 430:452 However, the role of fructose, the most enigmatic component of carbohydrate metabolism in fetal-placental tissues, is largely ignored since it is not metabolized via the glycolytic pathway or the Krebs cycle as an energy source. 27655785 4 26 theme biosynthesis 922:933 arg1 pathway 935:941 the hexosamine biosynthesis pathway 907:941 the hexosamine biosynthesis pathway 907:941 The phosphorylation for activation of this cascade is mediated by O-GlcNAcylation from UDP-N-acetylglucosamine (UDP-GlcNAc), a primary product of the hexosamine biosynthesis pathway. 27655785 0 27 from Phosphorylation 75:89 arg1 Cells 154:158 Ovine Trophectoderm Cells 134:158 Ovine Trophectoderm Cells 134:158 Functional Roles of Fructose: Crosstalk between O-Linked Glycosylation and Phosphorylation of Akt-TSC2-MTOR Cell Signaling Cascade in Ovine Trophectoderm Cells. 27655785 5 28 theme embryonic/fetal 1013:1027 arg1 growth 1029:1034 growth 1029:1034 growth 1029:1034 These results reveal novel functional roles of fructose in promoting embryonic/fetal growth and development during pregnancy, and also provide new insight into understanding the relationship between excessive fructose intake and metabolic disorders. 27655785 2 29 theme fructose 361:368 arg1 role 353:356 the role 349:356 the role of fructose, the most enigmatic component of carbohydrate metabolism in fetal-placental tissues, 349:453 However, the role of fructose, the most enigmatic component of carbohydrate metabolism in fetal-placental tissues, is largely ignored since it is not metabolized via the glycolytic pathway or the Krebs cycle as an energy source. 27655785 3 30 theme cascade 752:758 arg1 activation 710:719 activation 710:719 activation of the Akt-TSC2-MTOR signaling cascade 710:758 Here we provided evidence for biological functions of fructose that affect proliferative behavior of the conceptus trophectoderm/chorion via activation of the Akt-TSC2-MTOR signaling cascade. 27655785 0 31 theme Trophectoderm 140:152 arg1 Cells 154:158 Ovine Trophectoderm Cells 134:158 Ovine Trophectoderm Cells 134:158 Functional Roles of Fructose: Crosstalk between O-Linked Glycosylation and Phosphorylation of Akt-TSC2-MTOR Cell Signaling Cascade in Ovine Trophectoderm Cells. 27655785 1 32 dep cows 220:223 arg1 e.g. 214:217 e.g. 214:217 e.g. 214:217 During pregnancy, the placentae of ungulate mammals (e.g., cows, sheep, and pigs) convert glucose into fructose which is the most abundant hexose sugar in fetal fluids and blood. 27655785 2 33 theme enigmatic 380:388 arg1 component 390:398 the most enigmatic component 371:398 the most enigmatic component of carbohydrate metabolism in fetal-placental tissues 371:452 However, the role of fructose, the most enigmatic component of carbohydrate metabolism in fetal-placental tissues, is largely ignored since it is not metabolized via the glycolytic pathway or the Krebs cycle as an energy source. 27655785 2 33 theme enigmatic 380:388 arg1 fructose 361:368 fructose 361:368 fructose 361:368 However, the role of fructose, the most enigmatic component of carbohydrate metabolism in fetal-placental tissues, is largely ignored since it is not metabolized via the glycolytic pathway or the Krebs cycle as an energy source. 27655785 3 34 theme signaling 742:750 arg1 cascade 752:758 the Akt-TSC2-MTOR signaling cascade 724:758 the Akt-TSC2-MTOR signaling cascade 724:758 Here we provided evidence for biological functions of fructose that affect proliferative behavior of the conceptus trophectoderm/chorion via activation of the Akt-TSC2-MTOR signaling cascade. 27655785 0 35 theme O-Linked 48:55 arg1 Glycosylation 57:69 O-Linked Glycosylation 48:69 O-Linked Glycosylation 48:69 Functional Roles of Fructose: Crosstalk between O-Linked Glycosylation and Phosphorylation of Akt-TSC2-MTOR Cell Signaling Cascade in Ovine Trophectoderm Cells. 27655785 5 36 theme metabolic 1173:1181 arg1 disorders 1183:1191 metabolic disorders 1173:1191 metabolic disorders 1173:1191 These results reveal novel functional roles of fructose in promoting embryonic/fetal growth and development during pregnancy, and also provide new insight into understanding the relationship between excessive fructose intake and metabolic disorders. 27655785 0 37 from Glycosylation 57:69 arg1 Cells 154:158 Ovine Trophectoderm Cells 134:158 Ovine Trophectoderm Cells 134:158 Functional Roles of Fructose: Crosstalk between O-Linked Glycosylation and Phosphorylation of Akt-TSC2-MTOR Cell Signaling Cascade in Ovine Trophectoderm Cells. 27655785 1 38 from sugar 307:311 arg1 blood 333:337 blood 333:337 blood 333:337 During pregnancy, the placentae of ungulate mammals (e.g., cows, sheep, and pigs) convert glucose into fructose which is the most abundant hexose sugar in fetal fluids and blood. 27655785 1 38 from sugar 307:311 arg1 fluids 322:327 fetal fluids 316:327 fetal fluids 316:327 During pregnancy, the placentae of ungulate mammals (e.g., cows, sheep, and pigs) convert glucose into fructose which is the most abundant hexose sugar in fetal fluids and blood. 27655785 3 39 theme Akt-TSC2-MTOR 728:740 arg1 cascade 752:758 the Akt-TSC2-MTOR signaling cascade 724:758 the Akt-TSC2-MTOR signaling cascade 724:758 Here we provided evidence for biological functions of fructose that affect proliferative behavior of the conceptus trophectoderm/chorion via activation of the Akt-TSC2-MTOR signaling cascade. 27655785 3 40 theme proliferative 644:656 arg1 behavior 658:665 proliferative behavior 644:665 proliferative behavior of the conceptus trophectoderm/chorion 644:704 Here we provided evidence for biological functions of fructose that affect proliferative behavior of the conceptus trophectoderm/chorion via activation of the Akt-TSC2-MTOR signaling cascade. 27655785 2 41 theme carbohydrate 403:414 arg1 metabolism 416:425 carbohydrate metabolism 403:425 carbohydrate metabolism in fetal-placental tissues 403:452 However, the role of fructose, the most enigmatic component of carbohydrate metabolism in fetal-placental tissues, is largely ignored since it is not metabolized via the glycolytic pathway or the Krebs cycle as an energy source. 27655785 4 42 theme cascade 804:810 arg1 activation 785:794 activation 785:794 activation of this cascade 785:810 The phosphorylation for activation of this cascade is mediated by O-GlcNAcylation from UDP-N-acetylglucosamine (UDP-GlcNAc), a primary product of the hexosamine biosynthesis pathway. 27655785 5 43 theme new 1087:1089 arg1 insight 1091:1097 new insight 1087:1097 new insight into understanding the relationship between excessive fructose intake and metabolic disorders 1087:1191 These results reveal novel functional roles of fructose in promoting embryonic/fetal growth and development during pregnancy, and also provide new insight into understanding the relationship between excessive fructose intake and metabolic disorders. 27655785 1 44 theme abundant 291:298 arg1 fructose 264:271 fructose 264:271 fructose which is the most abundant hexose sugar in fetal fluids and blood 264:337 During pregnancy, the placentae of ungulate mammals (e.g., cows, sheep, and pigs) convert glucose into fructose which is the most abundant hexose sugar in fetal fluids and blood. 27655785 1 44 theme abundant 291:298 arg1 sugar 307:311 the most abundant hexose sugar 282:311 the most abundant hexose sugar in fetal fluids and blood 282:337 During pregnancy, the placentae of ungulate mammals (e.g., cows, sheep, and pigs) convert glucose into fructose which is the most abundant hexose sugar in fetal fluids and blood. 27655785 3 45 theme fructose 623:630 arg1 functions 610:618 biological functions 599:618 biological functions of fructose that affect proliferative behavior of the conceptus trophectoderm/chorion via activation of the Akt-TSC2-MTOR signaling cascade 599:758 Here we provided evidence for biological functions of fructose that affect proliferative behavior of the conceptus trophectoderm/chorion via activation of the Akt-TSC2-MTOR signaling cascade. 27655785 2 46 theme glycolytic 510:519 arg1 pathway 521:527 the glycolytic pathway 506:527 the glycolytic pathway 506:527 However, the role of fructose, the most enigmatic component of carbohydrate metabolism in fetal-placental tissues, is largely ignored since it is not metabolized via the glycolytic pathway or the Krebs cycle as an energy source. 27655785 3 47 theme biological 599:608 arg1 functions 610:618 biological functions 599:618 biological functions of fructose that affect proliferative behavior of the conceptus trophectoderm/chorion via activation of the Akt-TSC2-MTOR signaling cascade 599:758 Here we provided evidence for biological functions of fructose that affect proliferative behavior of the conceptus trophectoderm/chorion via activation of the Akt-TSC2-MTOR signaling cascade. 27655785 5 48 theme fructose 991:998 arg1 roles 982:986 novel functional roles 965:986 novel functional roles of fructose in promoting embryonic/fetal growth and development during pregnancy 965:1067 These results reveal novel functional roles of fructose in promoting embryonic/fetal growth and development during pregnancy, and also provide new insight into understanding the relationship between excessive fructose intake and metabolic disorders. 27655785 1 49 dep mammals 205:211 arg1 sheep 226:230 sheep 226:230 sheep 226:230 During pregnancy, the placentae of ungulate mammals (e.g., cows, sheep, and pigs) convert glucose into fructose which is the most abundant hexose sugar in fetal fluids and blood. 27655785 1 49 dep mammals 205:211 arg1 pigs 237:240 pigs 237:240 pigs 237:240 During pregnancy, the placentae of ungulate mammals (e.g., cows, sheep, and pigs) convert glucose into fructose which is the most abundant hexose sugar in fetal fluids and blood. 27655785 1 49 dep mammals 205:211 arg1 cows 220:223 cows 220:223 cows 220:223 During pregnancy, the placentae of ungulate mammals (e.g., cows, sheep, and pigs) convert glucose into fructose which is the most abundant hexose sugar in fetal fluids and blood. 27655785 2 50 theme metabolism 416:425 arg1 component 390:398 the most enigmatic component 371:398 the most enigmatic component of carbohydrate metabolism in fetal-placental tissues 371:452 However, the role of fructose, the most enigmatic component of carbohydrate metabolism in fetal-placental tissues, is largely ignored since it is not metabolized via the glycolytic pathway or the Krebs cycle as an energy source. 27655785 2 50 theme metabolism 416:425 arg1 fructose 361:368 fructose 361:368 fructose 361:368 However, the role of fructose, the most enigmatic component of carbohydrate metabolism in fetal-placental tissues, is largely ignored since it is not metabolized via the glycolytic pathway or the Krebs cycle as an energy source. 27655785 1 51 theme hexose 300:305 arg1 fructose 264:271 fructose 264:271 fructose which is the most abundant hexose sugar in fetal fluids and blood 264:337 During pregnancy, the placentae of ungulate mammals (e.g., cows, sheep, and pigs) convert glucose into fructose which is the most abundant hexose sugar in fetal fluids and blood. 27655785 1 51 theme hexose 300:305 arg1 sugar 307:311 the most abundant hexose sugar 282:311 the most abundant hexose sugar in fetal fluids and blood 282:337 During pregnancy, the placentae of ungulate mammals (e.g., cows, sheep, and pigs) convert glucose into fructose which is the most abundant hexose sugar in fetal fluids and blood. 27655785 4 52 from UDP-N-acetylglucosamine 848:870 arg1 O-GlcNAcylation 827:841 O-GlcNAcylation 827:841 O-GlcNAcylation from UDP-N-acetylglucosamine (UDP-GlcNAc), a primary product of the hexosamine biosynthesis pathway 827:941 The phosphorylation for activation of this cascade is mediated by O-GlcNAcylation from UDP-N-acetylglucosamine (UDP-GlcNAc), a primary product of the hexosamine biosynthesis pathway. 27655785 4 53 theme pathway 935:941 arg1 product 896:902 a primary product 886:902 a primary product of the hexosamine biosynthesis pathway 886:941 The phosphorylation for activation of this cascade is mediated by O-GlcNAcylation from UDP-N-acetylglucosamine (UDP-GlcNAc), a primary product of the hexosamine biosynthesis pathway. 27655785 4 53 theme pathway 935:941 arg1 UDP-N-acetylglucosamine 848:870 UDP-N-acetylglucosamine 848:870 UDP-N-acetylglucosamine (UDP-GlcNAc) 848:883 The phosphorylation for activation of this cascade is mediated by O-GlcNAcylation from UDP-N-acetylglucosamine (UDP-GlcNAc), a primary product of the hexosamine biosynthesis pathway. 25844059 1 0 theme deprotonated 176:187 arg1 glycopeptides 198:210 both protonated and deprotonated O-linked glycopeptides 156:210 both protonated and deprotonated O-linked glycopeptides from fetuin and κ-casein obtained upon collision induced dissociation (CID) and 193 nm ultraviolet photodissociation (UVPD) 156:334 A comparison of the fragmentation pathways of both protonated and deprotonated O-linked glycopeptides from fetuin and κ-casein obtained upon collision induced dissociation (CID) and 193 nm ultraviolet photodissociation (UVPD) in a linear ion trap is presented. 25844059 1 1 gly glycopeptides 198:210 arg1 fetuin 217:222 fetuin 217:222 fetuin 217:222 A comparison of the fragmentation pathways of both protonated and deprotonated O-linked glycopeptides from fetuin and κ-casein obtained upon collision induced dissociation (CID) and 193 nm ultraviolet photodissociation (UVPD) in a linear ion trap is presented. 25844059 1 1 gly glycopeptides 198:210 arg2 glycopeptides 198:210 both protonated and deprotonated O-linked glycopeptides 156:210 both protonated and deprotonated O-linked glycopeptides from fetuin and κ-casein obtained upon collision induced dissociation (CID) and 193 nm ultraviolet photodissociation (UVPD) 156:334 A comparison of the fragmentation pathways of both protonated and deprotonated O-linked glycopeptides from fetuin and κ-casein obtained upon collision induced dissociation (CID) and 193 nm ultraviolet photodissociation (UVPD) in a linear ion trap is presented. 25844059 1 1 gly glycopeptides 198:210 arg1 κ-casein 228:235 κ-casein 228:235 κ-casein 228:235 A comparison of the fragmentation pathways of both protonated and deprotonated O-linked glycopeptides from fetuin and κ-casein obtained upon collision induced dissociation (CID) and 193 nm ultraviolet photodissociation (UVPD) in a linear ion trap is presented. 25844059 1 2 theme O-linked 189:196 arg1 glycopeptides 198:210 both protonated and deprotonated O-linked glycopeptides 156:210 both protonated and deprotonated O-linked glycopeptides from fetuin and κ-casein obtained upon collision induced dissociation (CID) and 193 nm ultraviolet photodissociation (UVPD) 156:334 A comparison of the fragmentation pathways of both protonated and deprotonated O-linked glycopeptides from fetuin and κ-casein obtained upon collision induced dissociation (CID) and 193 nm ultraviolet photodissociation (UVPD) in a linear ion trap is presented. 25844059 4 3 theme unique 802:807 arg1 ion 818:820 unique fragment ion 802:820 unique fragment ion such as Y-type ions arising from cleavage at the N-terminus of proline 802:891 In addition, UVPD generated unique fragment ion such as Y-type ions arising from cleavage at the N-terminus of proline. 25844059 1 4 theme 193 292:294 arg1 nm 296:297 nm 296:297 nm 296:297 A comparison of the fragmentation pathways of both protonated and deprotonated O-linked glycopeptides from fetuin and κ-casein obtained upon collision induced dissociation (CID) and 193 nm ultraviolet photodissociation (UVPD) in a linear ion trap is presented. 25844059 5 5 theme glycopeptides 921:933 arg1 CID 894:896 CID 894:896 CID 894:896 CID and UVPD of protonated glycopeptides produced fragment ions solely from glycan cleavages. 25844059 5 5 theme glycopeptides 921:933 arg1 UVPD 902:905 UVPD 902:905 UVPD 902:905 CID and UVPD of protonated glycopeptides produced fragment ions solely from glycan cleavages. 25844059 3 6 gly glycopeptides 607:619 arg2 glycopeptides 607:619 deprotonated glycopeptides 594:619 deprotonated glycopeptides 594:619 UVPD of deprotonated glycopeptides generally produced the greatest array of fragment ions, thus affording the most diagnostic information about both glycan structure and peptide sequence. 25844059 1 7 theme nm 296:297 arg1 UVPD 330:333 UVPD 330:333 UVPD 330:333 A comparison of the fragmentation pathways of both protonated and deprotonated O-linked glycopeptides from fetuin and κ-casein obtained upon collision induced dissociation (CID) and 193 nm ultraviolet photodissociation (UVPD) in a linear ion trap is presented. 25844059 1 7 theme nm 296:297 arg1 photodissociation 311:327 193 nm ultraviolet photodissociation 292:327 193 nm ultraviolet photodissociation (UVPD) 292:334 A comparison of the fragmentation pathways of both protonated and deprotonated O-linked glycopeptides from fetuin and κ-casein obtained upon collision induced dissociation (CID) and 193 nm ultraviolet photodissociation (UVPD) in a linear ion trap is presented. 25844059 2 8 theme nano-liquid 536:546 arg1 nano-LC 564:570 nano-LC 564:570 nano-LC 564:570 A strategy using non-specific pronase digestion, zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC) solid phase extraction (SPE) enrichment, and nano-liquid chromatography (nano-LC) is employed. 25844059 2 8 theme nano-liquid 536:546 arg1 chromatography 548:561 nano-liquid chromatography 536:561 nano-liquid chromatography (nano-LC) 536:571 A strategy using non-specific pronase digestion, zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC) solid phase extraction (SPE) enrichment, and nano-liquid chromatography (nano-LC) is employed. 25844059 5 9 theme fragment 944:951 arg1 ions 953:956 fragment ions 944:956 fragment ions 944:956 CID and UVPD of protonated glycopeptides produced fragment ions solely from glycan cleavages. 25844059 1 10 theme glycopeptides 198:210 arg1 pathways 144:151 the fragmentation pathways 126:151 the fragmentation pathways of both protonated and deprotonated O-linked glycopeptides from fetuin and κ-casein obtained upon collision induced dissociation (CID) and 193 nm ultraviolet photodissociation (UVPD) 126:334 A comparison of the fragmentation pathways of both protonated and deprotonated O-linked glycopeptides from fetuin and κ-casein obtained upon collision induced dissociation (CID) and 193 nm ultraviolet photodissociation (UVPD) in a linear ion trap is presented. 25844059 4 11 from N-terminus 871:880 arg1 cleavage 855:862 cleavage 855:862 cleavage at the N-terminus of proline 855:891 In addition, UVPD generated unique fragment ion such as Y-type ions arising from cleavage at the N-terminus of proline. 25844059 4 12 theme fragment 809:816 arg1 ion 818:820 unique fragment ion 802:820 unique fragment ion such as Y-type ions arising from cleavage at the N-terminus of proline 802:891 In addition, UVPD generated unique fragment ion such as Y-type ions arising from cleavage at the N-terminus of proline. 25844059 3 13 theme peptide 756:762 arg1 sequence 764:771 peptide sequence 756:771 peptide sequence 756:771 UVPD of deprotonated glycopeptides generally produced the greatest array of fragment ions, thus affording the most diagnostic information about both glycan structure and peptide sequence. 25844059 4 14 theme proline 885:891 arg1 N-terminus 871:880 the N-terminus 867:880 the N-terminus of proline 867:891 In addition, UVPD generated unique fragment ion such as Y-type ions arising from cleavage at the N-terminus of proline. 25844059 5 15 theme glycan 970:975 arg1 cleavages 977:985 glycan cleavages 970:985 glycan cleavages 970:985 CID and UVPD of protonated glycopeptides produced fragment ions solely from glycan cleavages. 25844059 2 16 theme pronase 401:407 arg1 digestion 409:417 non-specific pronase digestion 388:417 non-specific pronase digestion 388:417 A strategy using non-specific pronase digestion, zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC) solid phase extraction (SPE) enrichment, and nano-liquid chromatography (nano-LC) is employed. 25844059 2 17 theme ZIC-HILIC 480:488 arg1 SPE 515:517 SPE 515:517 SPE 515:517 A strategy using non-specific pronase digestion, zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC) solid phase extraction (SPE) enrichment, and nano-liquid chromatography (nano-LC) is employed. 25844059 2 17 theme ZIC-HILIC 480:488 arg1 extraction 503:512 zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC) solid phase extraction 420:512 zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC) solid phase extraction (SPE) enrichment 420:529 A strategy using non-specific pronase digestion, zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC) solid phase extraction (SPE) enrichment, and nano-liquid chromatography (nano-LC) is employed. 25844059 1 18 theme ultraviolet 299:309 arg1 UVPD 330:333 UVPD 330:333 UVPD 330:333 A comparison of the fragmentation pathways of both protonated and deprotonated O-linked glycopeptides from fetuin and κ-casein obtained upon collision induced dissociation (CID) and 193 nm ultraviolet photodissociation (UVPD) in a linear ion trap is presented. 25844059 1 18 theme ultraviolet 299:309 arg1 photodissociation 311:327 193 nm ultraviolet photodissociation 292:327 193 nm ultraviolet photodissociation (UVPD) 292:334 A comparison of the fragmentation pathways of both protonated and deprotonated O-linked glycopeptides from fetuin and κ-casein obtained upon collision induced dissociation (CID) and 193 nm ultraviolet photodissociation (UVPD) in a linear ion trap is presented. 25844059 3 19 theme deprotonated 594:605 arg1 glycopeptides 607:619 deprotonated glycopeptides 594:619 deprotonated glycopeptides 594:619 UVPD of deprotonated glycopeptides generally produced the greatest array of fragment ions, thus affording the most diagnostic information about both glycan structure and peptide sequence. 25844059 2 20 theme non-specific 388:399 arg1 digestion 409:417 non-specific pronase digestion 388:417 non-specific pronase digestion 388:417 A strategy using non-specific pronase digestion, zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC) solid phase extraction (SPE) enrichment, and nano-liquid chromatography (nano-LC) is employed. 25844059 0 21 theme Fragmentation 27:39 arg1 Comparison 0:9 Comparison 0:9 Comparison of Glycopeptide Fragmentation by Collision 0:52 Comparison of Glycopeptide Fragmentation by Collision Induced Dissociation and Ultraviolet Photodissociation. 25844059 1 22 from pathways 144:151 arg1 fetuin 217:222 fetuin 217:222 fetuin 217:222 A comparison of the fragmentation pathways of both protonated and deprotonated O-linked glycopeptides from fetuin and κ-casein obtained upon collision induced dissociation (CID) and 193 nm ultraviolet photodissociation (UVPD) in a linear ion trap is presented. 25844059 1 22 from pathways 144:151 arg1 κ-casein 228:235 κ-casein 228:235 κ-casein 228:235 A comparison of the fragmentation pathways of both protonated and deprotonated O-linked glycopeptides from fetuin and κ-casein obtained upon collision induced dissociation (CID) and 193 nm ultraviolet photodissociation (UVPD) in a linear ion trap is presented. 25844059 2 23 theme liquid 457:462 arg1 chromatography 464:477 zwitterionic hydrophilic interaction liquid chromatography 420:477 zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC) solid phase extraction (SPE) enrichment 420:529 A strategy using non-specific pronase digestion, zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC) solid phase extraction (SPE) enrichment, and nano-liquid chromatography (nano-LC) is employed. 25844059 0 24 theme Glycopeptide 14:25 arg1 Fragmentation 27:39 Glycopeptide Fragmentation 14:39 Glycopeptide Fragmentation 14:39 Comparison of Glycopeptide Fragmentation by Collision Induced Dissociation and Ultraviolet Photodissociation. 25844059 1 25 link O-linked 189:196 arg1 glycopeptides 198:210 both protonated and deprotonated O-linked glycopeptides 156:210 both protonated and deprotonated O-linked glycopeptides from fetuin and κ-casein obtained upon collision induced dissociation (CID) and 193 nm ultraviolet photodissociation (UVPD) 156:334 A comparison of the fragmentation pathways of both protonated and deprotonated O-linked glycopeptides from fetuin and κ-casein obtained upon collision induced dissociation (CID) and 193 nm ultraviolet photodissociation (UVPD) in a linear ion trap is presented. 25844059 2 26 theme interaction 445:455 arg1 chromatography 464:477 zwitterionic hydrophilic interaction liquid chromatography 420:477 zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC) solid phase extraction (SPE) enrichment 420:529 A strategy using non-specific pronase digestion, zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC) solid phase extraction (SPE) enrichment, and nano-liquid chromatography (nano-LC) is employed. 25844059 4 27 theme Y-type 830:835 arg1 ions 837:840 Y-type ions 830:840 Y-type ions arising from cleavage at the N-terminus of proline 830:891 In addition, UVPD generated unique fragment ion such as Y-type ions arising from cleavage at the N-terminus of proline. 25844059 2 28 theme hydrophilic 433:443 arg1 chromatography 464:477 zwitterionic hydrophilic interaction liquid chromatography 420:477 zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC) solid phase extraction (SPE) enrichment 420:529 A strategy using non-specific pronase digestion, zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC) solid phase extraction (SPE) enrichment, and nano-liquid chromatography (nano-LC) is employed. 25844059 2 29 theme extraction 503:512 arg1 enrichment 520:529 zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC) solid phase extraction (SPE) enrichment 420:529 zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC) solid phase extraction (SPE) enrichment 420:529 A strategy using non-specific pronase digestion, zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC) solid phase extraction (SPE) enrichment, and nano-liquid chromatography (nano-LC) is employed. 25844059 3 30 theme ions 671:674 arg1 array 653:657 the greatest array 640:657 the greatest array of fragment ions 640:674 UVPD of deprotonated glycopeptides generally produced the greatest array of fragment ions, thus affording the most diagnostic information about both glycan structure and peptide sequence. 25844059 1 31 theme collision 251:259 arg1 CID 283:285 CID 283:285 CID 283:285 A comparison of the fragmentation pathways of both protonated and deprotonated O-linked glycopeptides from fetuin and κ-casein obtained upon collision induced dissociation (CID) and 193 nm ultraviolet photodissociation (UVPD) in a linear ion trap is presented. 25844059 1 31 theme collision 251:259 arg1 dissociation 269:280 collision induced dissociation 251:280 collision induced dissociation (CID) 251:286 A comparison of the fragmentation pathways of both protonated and deprotonated O-linked glycopeptides from fetuin and κ-casein obtained upon collision induced dissociation (CID) and 193 nm ultraviolet photodissociation (UVPD) in a linear ion trap is presented. 25844059 2 32 theme phase 497:501 arg1 SPE 515:517 SPE 515:517 SPE 515:517 A strategy using non-specific pronase digestion, zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC) solid phase extraction (SPE) enrichment, and nano-liquid chromatography (nano-LC) is employed. 25844059 2 32 theme phase 497:501 arg1 extraction 503:512 zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC) solid phase extraction 420:512 zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC) solid phase extraction (SPE) enrichment 420:529 A strategy using non-specific pronase digestion, zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC) solid phase extraction (SPE) enrichment, and nano-liquid chromatography (nano-LC) is employed. 25844059 3 33 theme glycopeptides 607:619 arg1 UVPD 586:589 UVPD 586:589 UVPD of deprotonated glycopeptides 586:619 UVPD of deprotonated glycopeptides generally produced the greatest array of fragment ions, thus affording the most diagnostic information about both glycan structure and peptide sequence. 25844059 1 34 theme fragmentation 130:142 arg1 pathways 144:151 the fragmentation pathways 126:151 the fragmentation pathways of both protonated and deprotonated O-linked glycopeptides from fetuin and κ-casein obtained upon collision induced dissociation (CID) and 193 nm ultraviolet photodissociation (UVPD) 126:334 A comparison of the fragmentation pathways of both protonated and deprotonated O-linked glycopeptides from fetuin and κ-casein obtained upon collision induced dissociation (CID) and 193 nm ultraviolet photodissociation (UVPD) in a linear ion trap is presented. 25844059 2 35 theme solid 491:495 arg1 SPE 515:517 SPE 515:517 SPE 515:517 A strategy using non-specific pronase digestion, zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC) solid phase extraction (SPE) enrichment, and nano-liquid chromatography (nano-LC) is employed. 25844059 2 35 theme solid 491:495 arg1 extraction 503:512 zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC) solid phase extraction 420:512 zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC) solid phase extraction (SPE) enrichment 420:529 A strategy using non-specific pronase digestion, zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC) solid phase extraction (SPE) enrichment, and nano-liquid chromatography (nano-LC) is employed. 25844059 3 36 theme glycan 735:740 arg1 structure 742:750 glycan structure 735:750 glycan structure 735:750 UVPD of deprotonated glycopeptides generally produced the greatest array of fragment ions, thus affording the most diagnostic information about both glycan structure and peptide sequence. 25844059 3 37 theme diagnostic 701:710 arg1 information 712:722 the most diagnostic information 692:722 the most diagnostic information about both glycan structure and peptide sequence 692:771 UVPD of deprotonated glycopeptides generally produced the greatest array of fragment ions, thus affording the most diagnostic information about both glycan structure and peptide sequence. 25844059 1 38 from κ-casein 228:235 arg1 glycopeptides 198:210 both protonated and deprotonated O-linked glycopeptides 156:210 both protonated and deprotonated O-linked glycopeptides from fetuin and κ-casein obtained upon collision induced dissociation (CID) and 193 nm ultraviolet photodissociation (UVPD) 156:334 A comparison of the fragmentation pathways of both protonated and deprotonated O-linked glycopeptides from fetuin and κ-casein obtained upon collision induced dissociation (CID) and 193 nm ultraviolet photodissociation (UVPD) in a linear ion trap is presented. 25844059 1 38 from κ-casein 228:235 arg1 pathways 144:151 the fragmentation pathways 126:151 the fragmentation pathways of both protonated and deprotonated O-linked glycopeptides from fetuin and κ-casein obtained upon collision induced dissociation (CID) and 193 nm ultraviolet photodissociation (UVPD) 126:334 A comparison of the fragmentation pathways of both protonated and deprotonated O-linked glycopeptides from fetuin and κ-casein obtained upon collision induced dissociation (CID) and 193 nm ultraviolet photodissociation (UVPD) in a linear ion trap is presented. 25844059 1 39 theme pathways 144:151 arg1 comparison 112:121 A comparison 110:121 A comparison of the fragmentation pathways of both protonated and deprotonated O-linked glycopeptides from fetuin and κ-casein obtained upon collision induced dissociation (CID) and 193 nm ultraviolet photodissociation (UVPD) in a linear ion trap 110:355 A comparison of the fragmentation pathways of both protonated and deprotonated O-linked glycopeptides from fetuin and κ-casein obtained upon collision induced dissociation (CID) and 193 nm ultraviolet photodissociation (UVPD) in a linear ion trap is presented. 25844059 1 40 theme linear 341:346 arg1 trap 352:355 a linear ion trap 339:355 a linear ion trap 339:355 A comparison of the fragmentation pathways of both protonated and deprotonated O-linked glycopeptides from fetuin and κ-casein obtained upon collision induced dissociation (CID) and 193 nm ultraviolet photodissociation (UVPD) in a linear ion trap is presented. 25844059 1 41 theme induced 261:267 arg1 CID 283:285 CID 283:285 CID 283:285 A comparison of the fragmentation pathways of both protonated and deprotonated O-linked glycopeptides from fetuin and κ-casein obtained upon collision induced dissociation (CID) and 193 nm ultraviolet photodissociation (UVPD) in a linear ion trap is presented. 25844059 1 41 theme induced 261:267 arg1 dissociation 269:280 collision induced dissociation 251:280 collision induced dissociation (CID) 251:286 A comparison of the fragmentation pathways of both protonated and deprotonated O-linked glycopeptides from fetuin and κ-casein obtained upon collision induced dissociation (CID) and 193 nm ultraviolet photodissociation (UVPD) in a linear ion trap is presented. 25844059 5 42 gly glycopeptides 921:933 arg2 glycopeptides 921:933 protonated glycopeptides 910:933 protonated glycopeptides 910:933 CID and UVPD of protonated glycopeptides produced fragment ions solely from glycan cleavages. 25844059 3 43 theme fragment 662:669 arg1 ions 671:674 fragment ions 662:674 fragment ions 662:674 UVPD of deprotonated glycopeptides generally produced the greatest array of fragment ions, thus affording the most diagnostic information about both glycan structure and peptide sequence. 25844059 1 44 from fetuin 217:222 arg1 glycopeptides 198:210 both protonated and deprotonated O-linked glycopeptides 156:210 both protonated and deprotonated O-linked glycopeptides from fetuin and κ-casein obtained upon collision induced dissociation (CID) and 193 nm ultraviolet photodissociation (UVPD) 156:334 A comparison of the fragmentation pathways of both protonated and deprotonated O-linked glycopeptides from fetuin and κ-casein obtained upon collision induced dissociation (CID) and 193 nm ultraviolet photodissociation (UVPD) in a linear ion trap is presented. 25844059 1 44 from fetuin 217:222 arg1 pathways 144:151 the fragmentation pathways 126:151 the fragmentation pathways of both protonated and deprotonated O-linked glycopeptides from fetuin and κ-casein obtained upon collision induced dissociation (CID) and 193 nm ultraviolet photodissociation (UVPD) 126:334 A comparison of the fragmentation pathways of both protonated and deprotonated O-linked glycopeptides from fetuin and κ-casein obtained upon collision induced dissociation (CID) and 193 nm ultraviolet photodissociation (UVPD) in a linear ion trap is presented. 25844059 0 45 theme Ultraviolet 79:89 arg1 Photodissociation 91:107 Ultraviolet Photodissociation 79:107 Ultraviolet Photodissociation 79:107 Comparison of Glycopeptide Fragmentation by Collision Induced Dissociation and Ultraviolet Photodissociation. 25844059 2 46 theme zwitterionic 420:431 arg1 chromatography 464:477 zwitterionic hydrophilic interaction liquid chromatography 420:477 zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC) solid phase extraction (SPE) enrichment 420:529 A strategy using non-specific pronase digestion, zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC) solid phase extraction (SPE) enrichment, and nano-liquid chromatography (nano-LC) is employed. 25844059 3 47 theme greatest 644:651 arg1 array 653:657 the greatest array 640:657 the greatest array of fragment ions 640:674 UVPD of deprotonated glycopeptides generally produced the greatest array of fragment ions, thus affording the most diagnostic information about both glycan structure and peptide sequence. 25844059 1 48 theme protonated 161:170 arg1 glycopeptides 198:210 both protonated and deprotonated O-linked glycopeptides 156:210 both protonated and deprotonated O-linked glycopeptides from fetuin and κ-casein obtained upon collision induced dissociation (CID) and 193 nm ultraviolet photodissociation (UVPD) 156:334 A comparison of the fragmentation pathways of both protonated and deprotonated O-linked glycopeptides from fetuin and κ-casein obtained upon collision induced dissociation (CID) and 193 nm ultraviolet photodissociation (UVPD) in a linear ion trap is presented. 25844059 1 49 from comparison 112:121 arg1 trap 352:355 a linear ion trap 339:355 a linear ion trap 339:355 A comparison of the fragmentation pathways of both protonated and deprotonated O-linked glycopeptides from fetuin and κ-casein obtained upon collision induced dissociation (CID) and 193 nm ultraviolet photodissociation (UVPD) in a linear ion trap is presented. 25844059 1 50 theme ion 348:350 arg1 trap 352:355 a linear ion trap 339:355 a linear ion trap 339:355 A comparison of the fragmentation pathways of both protonated and deprotonated O-linked glycopeptides from fetuin and κ-casein obtained upon collision induced dissociation (CID) and 193 nm ultraviolet photodissociation (UVPD) in a linear ion trap is presented. 25844059 2 51 theme chromatography 464:477 arg1 SPE 515:517 SPE 515:517 SPE 515:517 A strategy using non-specific pronase digestion, zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC) solid phase extraction (SPE) enrichment, and nano-liquid chromatography (nano-LC) is employed. 25844059 2 51 theme chromatography 464:477 arg1 extraction 503:512 zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC) solid phase extraction 420:512 zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC) solid phase extraction (SPE) enrichment 420:529 A strategy using non-specific pronase digestion, zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC) solid phase extraction (SPE) enrichment, and nano-liquid chromatography (nano-LC) is employed. 25844059 5 52 theme protonated 910:919 arg1 glycopeptides 921:933 protonated glycopeptides 910:933 protonated glycopeptides 910:933 CID and UVPD of protonated glycopeptides produced fragment ions solely from glycan cleavages. 27910787 2 0 theme dry 515:517 arg1 weight 519:524 3.89, 14.57, and 0.37 mg/g dry weight 488:524 3.89, 14.57, and 0.37 mg/g dry weight 488:524 The ergothioneine contents of fruiting bodies and Hi-Ergo and regular mycelia were 3.89, 14.57, and 0.37 mg/g dry weight, respectively. 27910787 2 0 theme dry 515:517 arg1 contents 423:430 The ergothioneine contents 405:430 The ergothioneine contents of fruiting bodies and Hi-Ergo and regular mycelia 405:481 The ergothioneine contents of fruiting bodies and Hi-Ergo and regular mycelia were 3.89, 14.57, and 0.37 mg/g dry weight, respectively. 27910787 1 1 theme antioxidant 368:378 arg1 properties 380:389 antioxidant properties 368:389 antioxidant properties 368:389 Pleurotus citrinopileatus mycelium was prepared with high ergothioneine (Hi-Ergo) content and its proximate composition, nonvolatile taste components, and antioxidant properties were studied. 27910787 7 2 used used 1271:1274 arg2 mycelium 1240:1247 Hi-Ergo mycelium 1232:1247 Hi-Ergo mycelium 1232:1247 Overall, Hi-Ergo mycelium could be beneficially used as a food-flavoring material or as a nutritional supplement. 27910787 7 2 used used 1271:1274 arg2 supplement 1325:1334 a nutritional supplement 1311:1334 a nutritional supplement 1311:1334 Overall, Hi-Ergo mycelium could be beneficially used as a food-flavoring material or as a nutritional supplement. 27910787 7 2 used used 1271:1274 arg2 material 1296:1303 a food-flavoring material 1279:1303 a food-flavoring material 1279:1303 Overall, Hi-Ergo mycelium could be beneficially used as a food-flavoring material or as a nutritional supplement. 27910787 4 3 theme Hi-Ergo 708:714 arg1 mycelium 716:723 Hi-Ergo mycelium 708:723 Hi-Ergo mycelium 708:723 However, Hi-Ergo mycelium contained the smallest amounts of total sugars and polyols (47.43 mg/g dry weight). 27910787 1 4 theme Hi-Ergo 286:292 arg1 content 295:301 high ergothioneine (Hi-Ergo) content 266:301 high ergothioneine (Hi-Ergo) content 266:301 Pleurotus citrinopileatus mycelium was prepared with high ergothioneine (Hi-Ergo) content and its proximate composition, nonvolatile taste components, and antioxidant properties were studied. 27910787 0 5 theme Mycelium 77:84 arg1 Components 18:27 Nonvolatile Taste Components 0:27 Nonvolatile Taste Components 0:27 Nonvolatile Taste Components and Antioxidant Properties of Fruiting Body and Mycelium with High Ergothioneine Content from the Culinary-Medicinal Golden Oyster Mushroom Pleurotus citrinopileatus (Agaricomycetes). 27910787 0 5 theme Mycelium 77:84 arg1 Properties 45:54 Antioxidant Properties 33:54 Antioxidant Properties 33:54 Nonvolatile Taste Components and Antioxidant Properties of Fruiting Body and Mycelium with High Ergothioneine Content from the Culinary-Medicinal Golden Oyster Mushroom Pleurotus citrinopileatus (Agaricomycetes). 27910787 6 6 theme reducing 1046:1053 arg1 power 1055:1059 reducing power 1046:1059 reducing power 1046:1059 On the basis of the half-maximal effective concentration values obtained, the 70% ethanolic extract from Hi-Ergo mycelium showed the most effective antioxidant activity, reducing power, and scavenging ability, whereas the fruiting body showed the most effective antioxidant activity, chelating ability, and Trolox-equivalent antioxidant capacity. 27910787 0 7 from citrinopileatus 179:193 arg1 Content 110:116 High Ergothioneine Content 91:116 High Ergothioneine Content from the Culinary-Medicinal Golden Oyster Mushroom Pleurotus citrinopileatus (Agaricomycetes) 91:210 Nonvolatile Taste Components and Antioxidant Properties of Fruiting Body and Mycelium with High Ergothioneine Content from the Culinary-Medicinal Golden Oyster Mushroom Pleurotus citrinopileatus (Agaricomycetes). 27910787 0 8 theme Ergothioneine 96:108 arg1 Content 110:116 High Ergothioneine Content 91:116 High Ergothioneine Content from the Culinary-Medicinal Golden Oyster Mushroom Pleurotus citrinopileatus (Agaricomycetes) 91:210 Nonvolatile Taste Components and Antioxidant Properties of Fruiting Body and Mycelium with High Ergothioneine Content from the Culinary-Medicinal Golden Oyster Mushroom Pleurotus citrinopileatus (Agaricomycetes). 27910787 6 9 theme antioxidant 1201:1211 arg1 capacity 1213:1220 Trolox-equivalent antioxidant capacity 1183:1220 Trolox-equivalent antioxidant capacity 1183:1220 On the basis of the half-maximal effective concentration values obtained, the 70% ethanolic extract from Hi-Ergo mycelium showed the most effective antioxidant activity, reducing power, and scavenging ability, whereas the fruiting body showed the most effective antioxidant activity, chelating ability, and Trolox-equivalent antioxidant capacity. 27910787 3 10 theme dietary 573:579 arg1 fiber 581:585 dietary fiber 573:585 dietary fiber 573:585 Hi-Ergo mycelium contained more dietary fiber, soluble polysaccharides, and ash but less carbohydrates, reducing sugar, fiber, and fat than regular mycelium. 27910787 4 11 theme total 759:763 arg1 sugars 765:770 total sugars 759:770 total sugars 759:770 However, Hi-Ergo mycelium contained the smallest amounts of total sugars and polyols (47.43 mg/g dry weight). 27910787 0 12 theme High 91:94 arg1 Content 110:116 High Ergothioneine Content 91:116 High Ergothioneine Content from the Culinary-Medicinal Golden Oyster Mushroom Pleurotus citrinopileatus (Agaricomycetes) 91:210 Nonvolatile Taste Components and Antioxidant Properties of Fruiting Body and Mycelium with High Ergothioneine Content from the Culinary-Medicinal Golden Oyster Mushroom Pleurotus citrinopileatus (Agaricomycetes). 27910787 6 13 theme scavenging 1066:1075 arg1 ability 1077:1083 scavenging ability 1066:1083 scavenging ability 1066:1083 On the basis of the half-maximal effective concentration values obtained, the 70% ethanolic extract from Hi-Ergo mycelium showed the most effective antioxidant activity, reducing power, and scavenging ability, whereas the fruiting body showed the most effective antioxidant activity, chelating ability, and Trolox-equivalent antioxidant capacity. 27910787 6 14 theme chelating 1160:1168 arg1 ability 1170:1176 chelating ability 1160:1176 chelating ability 1160:1176 On the basis of the half-maximal effective concentration values obtained, the 70% ethanolic extract from Hi-Ergo mycelium showed the most effective antioxidant activity, reducing power, and scavenging ability, whereas the fruiting body showed the most effective antioxidant activity, chelating ability, and Trolox-equivalent antioxidant capacity. 27910787 7 15 theme nutritional 1313:1323 arg1 supplement 1325:1334 a nutritional supplement 1311:1334 a nutritional supplement 1311:1334 Overall, Hi-Ergo mycelium could be beneficially used as a food-flavoring material or as a nutritional supplement. 27910787 7 15 theme nutritional 1313:1323 arg1 mycelium 1240:1247 Hi-Ergo mycelium 1232:1247 Hi-Ergo mycelium 1232:1247 Overall, Hi-Ergo mycelium could be beneficially used as a food-flavoring material or as a nutritional supplement. 27910787 2 16 theme bodies 444:449 arg1 weight 519:524 3.89, 14.57, and 0.37 mg/g dry weight 488:524 3.89, 14.57, and 0.37 mg/g dry weight 488:524 The ergothioneine contents of fruiting bodies and Hi-Ergo and regular mycelia were 3.89, 14.57, and 0.37 mg/g dry weight, respectively. 27910787 2 16 theme bodies 444:449 arg1 contents 423:430 The ergothioneine contents 405:430 The ergothioneine contents of fruiting bodies and Hi-Ergo and regular mycelia 405:481 The ergothioneine contents of fruiting bodies and Hi-Ergo and regular mycelia were 3.89, 14.57, and 0.37 mg/g dry weight, respectively. 27910787 3 17 theme more 568:571 arg1 carbohydrates 630:642 more dietary fiber, soluble polysaccharides, and ash but less carbohydrates 568:642 more dietary fiber, soluble polysaccharides, and ash but less carbohydrates 568:642 Hi-Ergo mycelium contained more dietary fiber, soluble polysaccharides, and ash but less carbohydrates, reducing sugar, fiber, and fat than regular mycelium. 27910787 2 18 theme fruiting 435:442 arg1 bodies 444:449 fruiting bodies 435:449 fruiting bodies 435:449 The ergothioneine contents of fruiting bodies and Hi-Ergo and regular mycelia were 3.89, 14.57, and 0.37 mg/g dry weight, respectively. 27910787 0 19 theme Taste 12:16 arg1 Components 18:27 Nonvolatile Taste Components 0:27 Nonvolatile Taste Components 0:27 Nonvolatile Taste Components and Antioxidant Properties of Fruiting Body and Mycelium with High Ergothioneine Content from the Culinary-Medicinal Golden Oyster Mushroom Pleurotus citrinopileatus (Agaricomycetes). 27910787 4 20 contain contained 725:733 arg2 amounts 748:754 the smallest amounts 735:754 the smallest amounts of total sugars and polyols (47.43 mg/g dry weight) 735:806 However, Hi-Ergo mycelium contained the smallest amounts of total sugars and polyols (47.43 mg/g dry weight). 27910787 4 20 contain contained 725:733 arg2 polyols 776:782 polyols 776:782 polyols (47.43 mg/g dry weight) 776:806 However, Hi-Ergo mycelium contained the smallest amounts of total sugars and polyols (47.43 mg/g dry weight). 27910787 4 20 contain contained 725:733 arg2 sugars 765:770 total sugars 759:770 total sugars 759:770 However, Hi-Ergo mycelium contained the smallest amounts of total sugars and polyols (47.43 mg/g dry weight). 27910787 4 20 contain contained 725:733 arg1 mycelium 716:723 Hi-Ergo mycelium 708:723 Hi-Ergo mycelium 708:723 However, Hi-Ergo mycelium contained the smallest amounts of total sugars and polyols (47.43 mg/g dry weight). 27910787 4 20 contain contained 725:733 arg2 weight 800:805 47.43 mg/g dry weight 785:805 47.43 mg/g dry weight 785:805 However, Hi-Ergo mycelium contained the smallest amounts of total sugars and polyols (47.43 mg/g dry weight). 27910787 6 21 from mycelium 989:996 arg1 extract 968:974 the 70% ethanolic extract 950:974 the 70% ethanolic extract from Hi-Ergo mycelium 950:996 On the basis of the half-maximal effective concentration values obtained, the 70% ethanolic extract from Hi-Ergo mycelium showed the most effective antioxidant activity, reducing power, and scavenging ability, whereas the fruiting body showed the most effective antioxidant activity, chelating ability, and Trolox-equivalent antioxidant capacity. 27910787 2 22 dep mg/g 510:513 arg1 14.57 494:498 14.57 494:498 14.57 494:498 The ergothioneine contents of fruiting bodies and Hi-Ergo and regular mycelia were 3.89, 14.57, and 0.37 mg/g dry weight, respectively. 27910787 2 22 dep mg/g 510:513 arg1 0.37 505:508 0.37 505:508 0.37 505:508 The ergothioneine contents of fruiting bodies and Hi-Ergo and regular mycelia were 3.89, 14.57, and 0.37 mg/g dry weight, respectively. 27910787 5 23 theme umami 863:867 arg1 taste 869:873 the most intense umami taste 846:873 the most intense umami taste 846:873 In addition, Hi-Ergo mycelium showed the most intense umami taste. 27910787 0 24 theme Nonvolatile 0:10 arg1 Components 18:27 Nonvolatile Taste Components 0:27 Nonvolatile Taste Components 0:27 Nonvolatile Taste Components and Antioxidant Properties of Fruiting Body and Mycelium with High Ergothioneine Content from the Culinary-Medicinal Golden Oyster Mushroom Pleurotus citrinopileatus (Agaricomycetes). 27910787 6 25 theme ethanolic 958:966 arg1 extract 968:974 the 70% ethanolic extract 950:974 the 70% ethanolic extract from Hi-Ergo mycelium 950:996 On the basis of the half-maximal effective concentration values obtained, the 70% ethanolic extract from Hi-Ergo mycelium showed the most effective antioxidant activity, reducing power, and scavenging ability, whereas the fruiting body showed the most effective antioxidant activity, chelating ability, and Trolox-equivalent antioxidant capacity. 27910787 6 26 theme antioxidant 1138:1148 arg1 activity 1150:1157 the most effective antioxidant activity 1119:1157 the most effective antioxidant activity 1119:1157 On the basis of the half-maximal effective concentration values obtained, the 70% ethanolic extract from Hi-Ergo mycelium showed the most effective antioxidant activity, reducing power, and scavenging ability, whereas the fruiting body showed the most effective antioxidant activity, chelating ability, and Trolox-equivalent antioxidant capacity. 27910787 4 27 theme polyols 776:782 arg1 weight 800:805 47.43 mg/g dry weight 785:805 47.43 mg/g dry weight 785:805 However, Hi-Ergo mycelium contained the smallest amounts of total sugars and polyols (47.43 mg/g dry weight). 27910787 4 27 theme polyols 776:782 arg1 polyols 776:782 polyols 776:782 polyols (47.43 mg/g dry weight) 776:806 However, Hi-Ergo mycelium contained the smallest amounts of total sugars and polyols (47.43 mg/g dry weight). 27910787 4 27 theme polyols 776:782 arg1 amounts 748:754 the smallest amounts 735:754 the smallest amounts of total sugars and polyols (47.43 mg/g dry weight) 735:806 However, Hi-Ergo mycelium contained the smallest amounts of total sugars and polyols (47.43 mg/g dry weight). 27910787 4 27 theme polyols 776:782 arg1 sugars 765:770 total sugars 759:770 total sugars 759:770 However, Hi-Ergo mycelium contained the smallest amounts of total sugars and polyols (47.43 mg/g dry weight). 27910787 1 28 theme Pleurotus 213:221 arg1 mycelium 239:246 Pleurotus citrinopileatus mycelium 213:246 Pleurotus citrinopileatus mycelium 213:246 Pleurotus citrinopileatus mycelium was prepared with high ergothioneine (Hi-Ergo) content and its proximate composition, nonvolatile taste components, and antioxidant properties were studied. 27910787 1 29 theme proximate 311:319 arg1 composition 321:331 its proximate composition 307:331 its proximate composition 307:331 Pleurotus citrinopileatus mycelium was prepared with high ergothioneine (Hi-Ergo) content and its proximate composition, nonvolatile taste components, and antioxidant properties were studied. 27910787 1 29 theme proximate 311:319 arg1 components 352:361 nonvolatile taste components 334:361 nonvolatile taste components 334:361 Pleurotus citrinopileatus mycelium was prepared with high ergothioneine (Hi-Ergo) content and its proximate composition, nonvolatile taste components, and antioxidant properties were studied. 27910787 0 30 theme Culinary-Medicinal 127:144 arg1 Agaricomycetes 196:209 Agaricomycetes 196:209 Agaricomycetes 196:209 Nonvolatile Taste Components and Antioxidant Properties of Fruiting Body and Mycelium with High Ergothioneine Content from the Culinary-Medicinal Golden Oyster Mushroom Pleurotus citrinopileatus (Agaricomycetes). 27910787 0 30 theme Culinary-Medicinal 127:144 arg1 citrinopileatus 179:193 the Culinary-Medicinal Golden Oyster Mushroom Pleurotus citrinopileatus 123:193 the Culinary-Medicinal Golden Oyster Mushroom Pleurotus citrinopileatus (Agaricomycetes) 123:210 Nonvolatile Taste Components and Antioxidant Properties of Fruiting Body and Mycelium with High Ergothioneine Content from the Culinary-Medicinal Golden Oyster Mushroom Pleurotus citrinopileatus (Agaricomycetes). 27910787 4 31 theme sugars 765:770 arg1 weight 800:805 47.43 mg/g dry weight 785:805 47.43 mg/g dry weight 785:805 However, Hi-Ergo mycelium contained the smallest amounts of total sugars and polyols (47.43 mg/g dry weight). 27910787 4 31 theme sugars 765:770 arg1 polyols 776:782 polyols 776:782 polyols (47.43 mg/g dry weight) 776:806 However, Hi-Ergo mycelium contained the smallest amounts of total sugars and polyols (47.43 mg/g dry weight). 27910787 4 31 theme sugars 765:770 arg1 amounts 748:754 the smallest amounts 735:754 the smallest amounts of total sugars and polyols (47.43 mg/g dry weight) 735:806 However, Hi-Ergo mycelium contained the smallest amounts of total sugars and polyols (47.43 mg/g dry weight). 27910787 4 31 theme sugars 765:770 arg1 sugars 765:770 total sugars 759:770 total sugars 759:770 However, Hi-Ergo mycelium contained the smallest amounts of total sugars and polyols (47.43 mg/g dry weight). 27910787 2 32 theme regular 467:473 arg1 mycelia 475:481 Hi-Ergo and regular mycelia 455:481 Hi-Ergo and regular mycelia 455:481 The ergothioneine contents of fruiting bodies and Hi-Ergo and regular mycelia were 3.89, 14.57, and 0.37 mg/g dry weight, respectively. 27910787 2 33 theme mycelia 475:481 arg1 weight 519:524 3.89, 14.57, and 0.37 mg/g dry weight 488:524 3.89, 14.57, and 0.37 mg/g dry weight 488:524 The ergothioneine contents of fruiting bodies and Hi-Ergo and regular mycelia were 3.89, 14.57, and 0.37 mg/g dry weight, respectively. 27910787 2 33 theme mycelia 475:481 arg1 contents 423:430 The ergothioneine contents 405:430 The ergothioneine contents of fruiting bodies and Hi-Ergo and regular mycelia 405:481 The ergothioneine contents of fruiting bodies and Hi-Ergo and regular mycelia were 3.89, 14.57, and 0.37 mg/g dry weight, respectively. 27910787 6 34 theme 70 954:955 arg1 % 956:956 % 956:956 % 956:956 On the basis of the half-maximal effective concentration values obtained, the 70% ethanolic extract from Hi-Ergo mycelium showed the most effective antioxidant activity, reducing power, and scavenging ability, whereas the fruiting body showed the most effective antioxidant activity, chelating ability, and Trolox-equivalent antioxidant capacity. 27910787 6 35 dep values 933:938 arg1 the 879:881 the 879:881 the 879:881 On the basis of the half-maximal effective concentration values obtained, the 70% ethanolic extract from Hi-Ergo mycelium showed the most effective antioxidant activity, reducing power, and scavenging ability, whereas the fruiting body showed the most effective antioxidant activity, chelating ability, and Trolox-equivalent antioxidant capacity. 27910787 6 35 dep values 933:938 arg1 basis 883:887 basis 883:887 basis 883:887 On the basis of the half-maximal effective concentration values obtained, the 70% ethanolic extract from Hi-Ergo mycelium showed the most effective antioxidant activity, reducing power, and scavenging ability, whereas the fruiting body showed the most effective antioxidant activity, chelating ability, and Trolox-equivalent antioxidant capacity. 27910787 3 36 theme soluble 588:594 arg1 polysaccharides 596:610 soluble polysaccharides 588:610 soluble polysaccharides 588:610 Hi-Ergo mycelium contained more dietary fiber, soluble polysaccharides, and ash but less carbohydrates, reducing sugar, fiber, and fat than regular mycelium. 27910787 6 37 theme half-maximal 896:907 arg1 values 933:938 the half-maximal effective concentration values 892:938 the half-maximal effective concentration values obtained 892:947 On the basis of the half-maximal effective concentration values obtained, the 70% ethanolic extract from Hi-Ergo mycelium showed the most effective antioxidant activity, reducing power, and scavenging ability, whereas the fruiting body showed the most effective antioxidant activity, chelating ability, and Trolox-equivalent antioxidant capacity. 27910787 3 38 theme Hi-Ergo 541:547 arg1 mycelium 549:556 Hi-Ergo mycelium 541:556 Hi-Ergo mycelium 541:556 Hi-Ergo mycelium contained more dietary fiber, soluble polysaccharides, and ash but less carbohydrates, reducing sugar, fiber, and fat than regular mycelium. 27910787 7 39 theme food-flavoring 1281:1294 arg1 material 1296:1303 a food-flavoring material 1279:1303 a food-flavoring material 1279:1303 Overall, Hi-Ergo mycelium could be beneficially used as a food-flavoring material or as a nutritional supplement. 27910787 7 39 theme food-flavoring 1281:1294 arg1 mycelium 1240:1247 Hi-Ergo mycelium 1232:1247 Hi-Ergo mycelium 1232:1247 Overall, Hi-Ergo mycelium could be beneficially used as a food-flavoring material or as a nutritional supplement. 27910787 0 40 theme Oyster 153:158 arg1 Agaricomycetes 196:209 Agaricomycetes 196:209 Agaricomycetes 196:209 Nonvolatile Taste Components and Antioxidant Properties of Fruiting Body and Mycelium with High Ergothioneine Content from the Culinary-Medicinal Golden Oyster Mushroom Pleurotus citrinopileatus (Agaricomycetes). 27910787 0 40 theme Oyster 153:158 arg1 citrinopileatus 179:193 the Culinary-Medicinal Golden Oyster Mushroom Pleurotus citrinopileatus 123:193 the Culinary-Medicinal Golden Oyster Mushroom Pleurotus citrinopileatus (Agaricomycetes) 123:210 Nonvolatile Taste Components and Antioxidant Properties of Fruiting Body and Mycelium with High Ergothioneine Content from the Culinary-Medicinal Golden Oyster Mushroom Pleurotus citrinopileatus (Agaricomycetes). 27910787 2 41 theme Hi-Ergo 455:461 arg1 mycelia 475:481 Hi-Ergo and regular mycelia 455:481 Hi-Ergo and regular mycelia 455:481 The ergothioneine contents of fruiting bodies and Hi-Ergo and regular mycelia were 3.89, 14.57, and 0.37 mg/g dry weight, respectively. 27910787 0 42 theme Antioxidant 33:43 arg1 Properties 45:54 Antioxidant Properties 33:54 Antioxidant Properties 33:54 Nonvolatile Taste Components and Antioxidant Properties of Fruiting Body and Mycelium with High Ergothioneine Content from the Culinary-Medicinal Golden Oyster Mushroom Pleurotus citrinopileatus (Agaricomycetes). 27910787 1 43 theme nonvolatile 334:344 arg1 composition 321:331 its proximate composition 307:331 its proximate composition 307:331 Pleurotus citrinopileatus mycelium was prepared with high ergothioneine (Hi-Ergo) content and its proximate composition, nonvolatile taste components, and antioxidant properties were studied. 27910787 1 43 theme nonvolatile 334:344 arg1 components 352:361 nonvolatile taste components 334:361 nonvolatile taste components 334:361 Pleurotus citrinopileatus mycelium was prepared with high ergothioneine (Hi-Ergo) content and its proximate composition, nonvolatile taste components, and antioxidant properties were studied. 27910787 0 44 theme Golden 146:151 arg1 Agaricomycetes 196:209 Agaricomycetes 196:209 Agaricomycetes 196:209 Nonvolatile Taste Components and Antioxidant Properties of Fruiting Body and Mycelium with High Ergothioneine Content from the Culinary-Medicinal Golden Oyster Mushroom Pleurotus citrinopileatus (Agaricomycetes). 27910787 0 44 theme Golden 146:151 arg1 citrinopileatus 179:193 the Culinary-Medicinal Golden Oyster Mushroom Pleurotus citrinopileatus 123:193 the Culinary-Medicinal Golden Oyster Mushroom Pleurotus citrinopileatus (Agaricomycetes) 123:210 Nonvolatile Taste Components and Antioxidant Properties of Fruiting Body and Mycelium with High Ergothioneine Content from the Culinary-Medicinal Golden Oyster Mushroom Pleurotus citrinopileatus (Agaricomycetes). 27910787 6 45 theme Hi-Ergo 981:987 arg1 mycelium 989:996 Hi-Ergo mycelium 981:996 Hi-Ergo mycelium 981:996 On the basis of the half-maximal effective concentration values obtained, the 70% ethanolic extract from Hi-Ergo mycelium showed the most effective antioxidant activity, reducing power, and scavenging ability, whereas the fruiting body showed the most effective antioxidant activity, chelating ability, and Trolox-equivalent antioxidant capacity. 27910787 1 46 dep Pleurotus 213:221 arg1 citrinopileatus 223:237 citrinopileatus 223:237 citrinopileatus 223:237 Pleurotus citrinopileatus mycelium was prepared with high ergothioneine (Hi-Ergo) content and its proximate composition, nonvolatile taste components, and antioxidant properties were studied. 27910787 6 47 theme antioxidant 1024:1034 arg1 activity 1036:1043 the most effective antioxidant activity 1005:1043 the most effective antioxidant activity 1005:1043 On the basis of the half-maximal effective concentration values obtained, the 70% ethanolic extract from Hi-Ergo mycelium showed the most effective antioxidant activity, reducing power, and scavenging ability, whereas the fruiting body showed the most effective antioxidant activity, chelating ability, and Trolox-equivalent antioxidant capacity. 27910787 0 48 theme Fruiting 59:66 arg1 Body 68:71 Fruiting Body 59:71 Fruiting Body 59:71 Nonvolatile Taste Components and Antioxidant Properties of Fruiting Body and Mycelium with High Ergothioneine Content from the Culinary-Medicinal Golden Oyster Mushroom Pleurotus citrinopileatus (Agaricomycetes). 27910787 1 49 theme taste 346:350 arg1 composition 321:331 its proximate composition 307:331 its proximate composition 307:331 Pleurotus citrinopileatus mycelium was prepared with high ergothioneine (Hi-Ergo) content and its proximate composition, nonvolatile taste components, and antioxidant properties were studied. 27910787 1 49 theme taste 346:350 arg1 components 352:361 nonvolatile taste components 334:361 nonvolatile taste components 334:361 Pleurotus citrinopileatus mycelium was prepared with high ergothioneine (Hi-Ergo) content and its proximate composition, nonvolatile taste components, and antioxidant properties were studied. 27910787 0 50 theme Pleurotus 169:177 arg1 Agaricomycetes 196:209 Agaricomycetes 196:209 Agaricomycetes 196:209 Nonvolatile Taste Components and Antioxidant Properties of Fruiting Body and Mycelium with High Ergothioneine Content from the Culinary-Medicinal Golden Oyster Mushroom Pleurotus citrinopileatus (Agaricomycetes). 27910787 0 50 theme Pleurotus 169:177 arg1 citrinopileatus 179:193 the Culinary-Medicinal Golden Oyster Mushroom Pleurotus citrinopileatus 123:193 the Culinary-Medicinal Golden Oyster Mushroom Pleurotus citrinopileatus (Agaricomycetes) 123:210 Nonvolatile Taste Components and Antioxidant Properties of Fruiting Body and Mycelium with High Ergothioneine Content from the Culinary-Medicinal Golden Oyster Mushroom Pleurotus citrinopileatus (Agaricomycetes). 27910787 6 51 theme % 956:956 arg1 extract 968:974 the 70% ethanolic extract 950:974 the 70% ethanolic extract from Hi-Ergo mycelium 950:996 On the basis of the half-maximal effective concentration values obtained, the 70% ethanolic extract from Hi-Ergo mycelium showed the most effective antioxidant activity, reducing power, and scavenging ability, whereas the fruiting body showed the most effective antioxidant activity, chelating ability, and Trolox-equivalent antioxidant capacity. 27910787 0 52 with Components 18:27 arg1 Content 110:116 High Ergothioneine Content 91:116 High Ergothioneine Content from the Culinary-Medicinal Golden Oyster Mushroom Pleurotus citrinopileatus (Agaricomycetes) 91:210 Nonvolatile Taste Components and Antioxidant Properties of Fruiting Body and Mycelium with High Ergothioneine Content from the Culinary-Medicinal Golden Oyster Mushroom Pleurotus citrinopileatus (Agaricomycetes). 27910787 0 53 theme Mushroom 160:167 arg1 Agaricomycetes 196:209 Agaricomycetes 196:209 Agaricomycetes 196:209 Nonvolatile Taste Components and Antioxidant Properties of Fruiting Body and Mycelium with High Ergothioneine Content from the Culinary-Medicinal Golden Oyster Mushroom Pleurotus citrinopileatus (Agaricomycetes). 27910787 0 53 theme Mushroom 160:167 arg1 citrinopileatus 179:193 the Culinary-Medicinal Golden Oyster Mushroom Pleurotus citrinopileatus 123:193 the Culinary-Medicinal Golden Oyster Mushroom Pleurotus citrinopileatus (Agaricomycetes) 123:210 Nonvolatile Taste Components and Antioxidant Properties of Fruiting Body and Mycelium with High Ergothioneine Content from the Culinary-Medicinal Golden Oyster Mushroom Pleurotus citrinopileatus (Agaricomycetes). 27910787 3 54 theme regular 681:687 arg1 mycelium 689:696 regular mycelium 681:696 regular mycelium 681:696 Hi-Ergo mycelium contained more dietary fiber, soluble polysaccharides, and ash but less carbohydrates, reducing sugar, fiber, and fat than regular mycelium. 27910787 3 55 dep more 568:571 arg1 fiber 581:585 dietary fiber 573:585 dietary fiber 573:585 Hi-Ergo mycelium contained more dietary fiber, soluble polysaccharides, and ash but less carbohydrates, reducing sugar, fiber, and fat than regular mycelium. 27910787 3 55 dep more 568:571 arg1 polysaccharides 596:610 soluble polysaccharides 588:610 soluble polysaccharides 588:610 Hi-Ergo mycelium contained more dietary fiber, soluble polysaccharides, and ash but less carbohydrates, reducing sugar, fiber, and fat than regular mycelium. 27910787 3 55 dep more 568:571 arg1 ash 617:619 ash 617:619 ash 617:619 Hi-Ergo mycelium contained more dietary fiber, soluble polysaccharides, and ash but less carbohydrates, reducing sugar, fiber, and fat than regular mycelium. 27910787 6 56 theme concentration 919:931 arg1 values 933:938 the half-maximal effective concentration values 892:938 the half-maximal effective concentration values obtained 892:947 On the basis of the half-maximal effective concentration values obtained, the 70% ethanolic extract from Hi-Ergo mycelium showed the most effective antioxidant activity, reducing power, and scavenging ability, whereas the fruiting body showed the most effective antioxidant activity, chelating ability, and Trolox-equivalent antioxidant capacity. 27910787 4 57 theme dry 796:798 arg1 weight 800:805 47.43 mg/g dry weight 785:805 47.43 mg/g dry weight 785:805 However, Hi-Ergo mycelium contained the smallest amounts of total sugars and polyols (47.43 mg/g dry weight). 27910787 4 57 theme dry 796:798 arg1 polyols 776:782 polyols 776:782 polyols (47.43 mg/g dry weight) 776:806 However, Hi-Ergo mycelium contained the smallest amounts of total sugars and polyols (47.43 mg/g dry weight). 27910787 3 58 theme less 625:628 arg1 carbohydrates 630:642 more dietary fiber, soluble polysaccharides, and ash but less carbohydrates 568:642 more dietary fiber, soluble polysaccharides, and ash but less carbohydrates 568:642 Hi-Ergo mycelium contained more dietary fiber, soluble polysaccharides, and ash but less carbohydrates, reducing sugar, fiber, and fat than regular mycelium. 27910787 4 59 theme smallest 739:746 arg1 weight 800:805 47.43 mg/g dry weight 785:805 47.43 mg/g dry weight 785:805 However, Hi-Ergo mycelium contained the smallest amounts of total sugars and polyols (47.43 mg/g dry weight). 27910787 4 59 theme smallest 739:746 arg1 polyols 776:782 polyols 776:782 polyols (47.43 mg/g dry weight) 776:806 However, Hi-Ergo mycelium contained the smallest amounts of total sugars and polyols (47.43 mg/g dry weight). 27910787 4 59 theme smallest 739:746 arg1 amounts 748:754 the smallest amounts 735:754 the smallest amounts of total sugars and polyols (47.43 mg/g dry weight) 735:806 However, Hi-Ergo mycelium contained the smallest amounts of total sugars and polyols (47.43 mg/g dry weight). 27910787 4 59 theme smallest 739:746 arg1 sugars 765:770 total sugars 759:770 total sugars 759:770 However, Hi-Ergo mycelium contained the smallest amounts of total sugars and polyols (47.43 mg/g dry weight). 27910787 6 60 theme effective 1128:1136 arg1 activity 1150:1157 the most effective antioxidant activity 1119:1157 the most effective antioxidant activity 1119:1157 On the basis of the half-maximal effective concentration values obtained, the 70% ethanolic extract from Hi-Ergo mycelium showed the most effective antioxidant activity, reducing power, and scavenging ability, whereas the fruiting body showed the most effective antioxidant activity, chelating ability, and Trolox-equivalent antioxidant capacity. 27910787 6 61 theme effective 1014:1022 arg1 activity 1036:1043 the most effective antioxidant activity 1005:1043 the most effective antioxidant activity 1005:1043 On the basis of the half-maximal effective concentration values obtained, the 70% ethanolic extract from Hi-Ergo mycelium showed the most effective antioxidant activity, reducing power, and scavenging ability, whereas the fruiting body showed the most effective antioxidant activity, chelating ability, and Trolox-equivalent antioxidant capacity. 27910787 2 62 dep weight 519:524 arg1 mg/g 510:513 mg/g 510:513 mg/g 510:513 The ergothioneine contents of fruiting bodies and Hi-Ergo and regular mycelia were 3.89, 14.57, and 0.37 mg/g dry weight, respectively. 27910787 4 63 theme mg/g 791:794 arg1 weight 800:805 47.43 mg/g dry weight 785:805 47.43 mg/g dry weight 785:805 However, Hi-Ergo mycelium contained the smallest amounts of total sugars and polyols (47.43 mg/g dry weight). 27910787 4 63 theme mg/g 791:794 arg1 polyols 776:782 polyols 776:782 polyols (47.43 mg/g dry weight) 776:806 However, Hi-Ergo mycelium contained the smallest amounts of total sugars and polyols (47.43 mg/g dry weight). 27910787 6 64 theme fruiting 1098:1105 arg1 body 1107:1110 the fruiting body 1094:1110 the fruiting body 1094:1110 On the basis of the half-maximal effective concentration values obtained, the 70% ethanolic extract from Hi-Ergo mycelium showed the most effective antioxidant activity, reducing power, and scavenging ability, whereas the fruiting body showed the most effective antioxidant activity, chelating ability, and Trolox-equivalent antioxidant capacity. 27910787 1 65 theme high 266:269 arg1 content 295:301 high ergothioneine (Hi-Ergo) content 266:301 high ergothioneine (Hi-Ergo) content 266:301 Pleurotus citrinopileatus mycelium was prepared with high ergothioneine (Hi-Ergo) content and its proximate composition, nonvolatile taste components, and antioxidant properties were studied. 27910787 7 66 theme Hi-Ergo 1232:1238 arg1 supplement 1325:1334 a nutritional supplement 1311:1334 a nutritional supplement 1311:1334 Overall, Hi-Ergo mycelium could be beneficially used as a food-flavoring material or as a nutritional supplement. 27910787 7 66 theme Hi-Ergo 1232:1238 arg1 mycelium 1240:1247 Hi-Ergo mycelium 1232:1247 Hi-Ergo mycelium 1232:1247 Overall, Hi-Ergo mycelium could be beneficially used as a food-flavoring material or as a nutritional supplement. 27910787 7 66 theme Hi-Ergo 1232:1238 arg1 material 1296:1303 a food-flavoring material 1279:1303 a food-flavoring material 1279:1303 Overall, Hi-Ergo mycelium could be beneficially used as a food-flavoring material or as a nutritional supplement. 27910787 6 67 theme Trolox-equivalent 1183:1199 arg1 capacity 1213:1220 Trolox-equivalent antioxidant capacity 1183:1220 Trolox-equivalent antioxidant capacity 1183:1220 On the basis of the half-maximal effective concentration values obtained, the 70% ethanolic extract from Hi-Ergo mycelium showed the most effective antioxidant activity, reducing power, and scavenging ability, whereas the fruiting body showed the most effective antioxidant activity, chelating ability, and Trolox-equivalent antioxidant capacity. 27910787 5 68 theme Hi-Ergo 822:828 arg1 mycelium 830:837 Hi-Ergo mycelium 822:837 Hi-Ergo mycelium 822:837 In addition, Hi-Ergo mycelium showed the most intense umami taste. 27910787 2 69 theme ergothioneine 409:421 arg1 weight 519:524 3.89, 14.57, and 0.37 mg/g dry weight 488:524 3.89, 14.57, and 0.37 mg/g dry weight 488:524 The ergothioneine contents of fruiting bodies and Hi-Ergo and regular mycelia were 3.89, 14.57, and 0.37 mg/g dry weight, respectively. 27910787 2 69 theme ergothioneine 409:421 arg1 contents 423:430 The ergothioneine contents 405:430 The ergothioneine contents of fruiting bodies and Hi-Ergo and regular mycelia 405:481 The ergothioneine contents of fruiting bodies and Hi-Ergo and regular mycelia were 3.89, 14.57, and 0.37 mg/g dry weight, respectively. 27910787 5 70 theme intense 855:861 arg1 taste 869:873 the most intense umami taste 846:873 the most intense umami taste 846:873 In addition, Hi-Ergo mycelium showed the most intense umami taste. 27910787 1 71 theme ergothioneine 271:283 arg1 content 295:301 high ergothioneine (Hi-Ergo) content 266:301 high ergothioneine (Hi-Ergo) content 266:301 Pleurotus citrinopileatus mycelium was prepared with high ergothioneine (Hi-Ergo) content and its proximate composition, nonvolatile taste components, and antioxidant properties were studied. 27910787 0 72 theme Body 68:71 arg1 Components 18:27 Nonvolatile Taste Components 0:27 Nonvolatile Taste Components 0:27 Nonvolatile Taste Components and Antioxidant Properties of Fruiting Body and Mycelium with High Ergothioneine Content from the Culinary-Medicinal Golden Oyster Mushroom Pleurotus citrinopileatus (Agaricomycetes). 27910787 0 72 theme Body 68:71 arg1 Properties 45:54 Antioxidant Properties 33:54 Antioxidant Properties 33:54 Nonvolatile Taste Components and Antioxidant Properties of Fruiting Body and Mycelium with High Ergothioneine Content from the Culinary-Medicinal Golden Oyster Mushroom Pleurotus citrinopileatus (Agaricomycetes). 27910787 6 73 theme effective 909:917 arg1 values 933:938 the half-maximal effective concentration values 892:938 the half-maximal effective concentration values obtained 892:947 On the basis of the half-maximal effective concentration values obtained, the 70% ethanolic extract from Hi-Ergo mycelium showed the most effective antioxidant activity, reducing power, and scavenging ability, whereas the fruiting body showed the most effective antioxidant activity, chelating ability, and Trolox-equivalent antioxidant capacity. 27910787 0 74 with Properties 45:54 arg1 Content 110:116 High Ergothioneine Content 91:116 High Ergothioneine Content from the Culinary-Medicinal Golden Oyster Mushroom Pleurotus citrinopileatus (Agaricomycetes) 91:210 Nonvolatile Taste Components and Antioxidant Properties of Fruiting Body and Mycelium with High Ergothioneine Content from the Culinary-Medicinal Golden Oyster Mushroom Pleurotus citrinopileatus (Agaricomycetes). 27910787 3 75 contain contained 558:566 arg2 carbohydrates 630:642 more dietary fiber, soluble polysaccharides, and ash but less carbohydrates 568:642 more dietary fiber, soluble polysaccharides, and ash but less carbohydrates 568:642 Hi-Ergo mycelium contained more dietary fiber, soluble polysaccharides, and ash but less carbohydrates, reducing sugar, fiber, and fat than regular mycelium. 27910787 3 75 contain contained 558:566 arg1 mycelium 549:556 Hi-Ergo mycelium 541:556 Hi-Ergo mycelium 541:556 Hi-Ergo mycelium contained more dietary fiber, soluble polysaccharides, and ash but less carbohydrates, reducing sugar, fiber, and fat than regular mycelium. 27416027 0 0 theme Non-Gut 73:79 arg1 Bacteria 81:88 Closely Related Non-Gut Bacteria 57:88 Closely Related Non-Gut Bacteria 57:88 Functional Comparison of Bacteria from the Human Gut and Closely Related Non-Gut Bacteria Reveals the Importance of Conjugation and a Paucity of Motility and Chemotaxis Functions in the Gut Environment. 27416027 1 1 theme densest 300:306 arg1 communities 318:328 the densest microbial communities 296:328 the densest microbial communities on earth 296:337 The human GI tract is a complex and still poorly understood environment, inhabited by one of the densest microbial communities on earth. 27416027 5 2 theme relatives 1057:1065 arg1 group 1005:1009 a group 1003:1009 a group of human gut bacteria and their close non-gut relatives 1003:1065 In order to identify other bacterial functions that are important in the human gut environment, we investigated the distribution of functional groups of proteins in a group of human gut bacteria and their close non-gut relatives. 27416027 5 2 theme relatives 1057:1065 arg1 relatives 1057:1065 their close non-gut relatives 1037:1065 their close non-gut relatives 1037:1065 In order to identify other bacterial functions that are important in the human gut environment, we investigated the distribution of functional groups of proteins in a group of human gut bacteria and their close non-gut relatives. 27416027 5 2 theme relatives 1057:1065 arg1 bacteria 1024:1031 human gut bacteria 1014:1031 human gut bacteria 1014:1031 In order to identify other bacterial functions that are important in the human gut environment, we investigated the distribution of functional groups of proteins in a group of human gut bacteria and their close non-gut relatives. 27416027 4 3 theme carbohydrate 665:676 arg1 metabolism 678:687 carbohydrate metabolism 665:687 carbohydrate metabolism 665:687 This can be illustrated by the presence of a highly expanded repertoire of proteins involved in carbohydrate metabolism, in phase with the large diversity of polysaccharides originating from the diet or from the host itself that can be encountered in this environment. 27416027 7 4 theme human 1450:1454 arg1 bacteria 1460:1467 the human gut bacteria 1446:1467 the human gut bacteria which had not been recognized in a global approach 1446:1518 We identified several functions that are overrepresented in the human gut bacteria which had not been recognized in a global approach. 27416027 0 5 theme Related 65:71 arg1 Bacteria 81:88 Closely Related Non-Gut Bacteria 57:88 Closely Related Non-Gut Bacteria 57:88 Functional Comparison of Bacteria from the Human Gut and Closely Related Non-Gut Bacteria Reveals the Importance of Conjugation and a Paucity of Motility and Chemotaxis Functions in the Gut Environment. 27416027 0 6 from Comparison 11:20 arg1 Gut 49:51 the Human Gut 39:51 the Human Gut 39:51 Functional Comparison of Bacteria from the Human Gut and Closely Related Non-Gut Bacteria Reveals the Importance of Conjugation and a Paucity of Motility and Chemotaxis Functions in the Gut Environment. 27416027 0 7 theme Chemotaxis 158:167 arg1 Paucity 134:140 a Paucity 132:140 a Paucity of Motility and Chemotaxis Functions 132:177 Functional Comparison of Bacteria from the Human Gut and Closely Related Non-Gut Bacteria Reveals the Importance of Conjugation and a Paucity of Motility and Chemotaxis Functions in the Gut Environment. 27416027 0 7 theme Chemotaxis 158:167 arg1 Importance 102:111 the Importance 98:111 the Importance of Conjugation 98:126 Functional Comparison of Bacteria from the Human Gut and Closely Related Non-Gut Bacteria Reveals the Importance of Conjugation and a Paucity of Motility and Chemotaxis Functions in the Gut Environment. 27416027 5 8 theme other 859:863 arg1 functions 875:883 other bacterial functions 859:883 other bacterial functions that are important in the human gut environment 859:931 In order to identify other bacterial functions that are important in the human gut environment, we investigated the distribution of functional groups of proteins in a group of human gut bacteria and their close non-gut relatives. 27416027 1 9 theme complex 227:233 arg1 environment 263:273 a complex and still poorly understood environment 225:273 a complex and still poorly understood environment 225:273 The human GI tract is a complex and still poorly understood environment, inhabited by one of the densest microbial communities on earth. 27416027 1 9 theme complex 227:233 arg1 tract 216:220 The human GI tract 203:220 The human GI tract 203:220 The human GI tract is a complex and still poorly understood environment, inhabited by one of the densest microbial communities on earth. 27416027 1 10 theme communities 318:328 arg1 communities 318:328 the densest microbial communities 296:328 the densest microbial communities on earth 296:337 The human GI tract is a complex and still poorly understood environment, inhabited by one of the densest microbial communities on earth. 27416027 1 10 theme communities 318:328 arg1 one 289:291 one 289:291 one 289:291 The human GI tract is a complex and still poorly understood environment, inhabited by one of the densest microbial communities on earth. 27416027 3 11 theme molecular 509:517 arg1 functions 519:527 specific molecular functions 500:527 specific molecular functions important in the human gut environment 500:566 Members of the gut microbiota perform specific molecular functions important in the human gut environment. 27416027 5 12 theme human 911:915 arg1 environment 921:931 the human gut environment 907:931 the human gut environment 907:931 In order to identify other bacterial functions that are important in the human gut environment, we investigated the distribution of functional groups of proteins in a group of human gut bacteria and their close non-gut relatives. 27416027 7 13 theme global 1504:1509 arg1 approach 1511:1518 a global approach 1502:1518 a global approach 1502:1518 We identified several functions that are overrepresented in the human gut bacteria which had not been recognized in a global approach. 27416027 0 14 theme Bacteria 81:88 arg1 Comparison 11:20 Functional Comparison 0:20 Functional Comparison of Bacteria from the Human Gut and Closely Related Non-Gut Bacteria 0:88 Functional Comparison of Bacteria from the Human Gut and Closely Related Non-Gut Bacteria Reveals the Importance of Conjugation and a Paucity of Motility and Chemotaxis Functions in the Gut Environment. 27416027 0 15 from Gut 49:51 arg1 Bacteria 25:32 Bacteria 25:32 Bacteria from the Human Gut 25:51 Functional Comparison of Bacteria from the Human Gut and Closely Related Non-Gut Bacteria Reveals the Importance of Conjugation and a Paucity of Motility and Chemotaxis Functions in the Gut Environment. 27416027 0 15 from Gut 49:51 arg1 Comparison 11:20 Functional Comparison 0:20 Functional Comparison of Bacteria from the Human Gut and Closely Related Non-Gut Bacteria 0:88 Functional Comparison of Bacteria from the Human Gut and Closely Related Non-Gut Bacteria Reveals the Importance of Conjugation and a Paucity of Motility and Chemotaxis Functions in the Gut Environment. 27416027 0 15 from Gut 49:51 arg1 Bacteria 81:88 Closely Related Non-Gut Bacteria 57:88 Closely Related Non-Gut Bacteria 57:88 Functional Comparison of Bacteria from the Human Gut and Closely Related Non-Gut Bacteria Reveals the Importance of Conjugation and a Paucity of Motility and Chemotaxis Functions in the Gut Environment. 27416027 7 16 theme several 1400:1406 arg1 functions 1408:1416 several functions 1400:1416 several functions that are overrepresented in the human gut bacteria which had not been recognized in a global approach 1400:1518 We identified several functions that are overrepresented in the human gut bacteria which had not been recognized in a global approach. 27416027 5 17 from distribution 954:965 arg1 group 1005:1009 a group 1003:1009 a group of human gut bacteria and their close non-gut relatives 1003:1065 In order to identify other bacterial functions that are important in the human gut environment, we investigated the distribution of functional groups of proteins in a group of human gut bacteria and their close non-gut relatives. 27416027 5 17 from distribution 954:965 arg1 relatives 1057:1065 their close non-gut relatives 1037:1065 their close non-gut relatives 1037:1065 In order to identify other bacterial functions that are important in the human gut environment, we investigated the distribution of functional groups of proteins in a group of human gut bacteria and their close non-gut relatives. 27416027 5 17 from distribution 954:965 arg1 bacteria 1024:1031 human gut bacteria 1014:1031 human gut bacteria 1014:1031 In order to identify other bacterial functions that are important in the human gut environment, we investigated the distribution of functional groups of proteins in a group of human gut bacteria and their close non-gut relatives. 27416027 5 18 theme close 1043:1047 arg1 relatives 1057:1065 their close non-gut relatives 1037:1065 their close non-gut relatives 1037:1065 In order to identify other bacterial functions that are important in the human gut environment, we investigated the distribution of functional groups of proteins in a group of human gut bacteria and their close non-gut relatives. 27416027 6 19 theme related 1217:1223 arg1 functions 1198:1206 functions 1198:1206 functions directly related to the gut environment 1198:1246 Complementary to earlier global comparisons between different ecosystems, this approach should allow a closer focus on a group of functions directly related to the gut environment while avoiding functions related to taxonomically divergent microbiota composition, which may or may not be relevant for gut homeostasis. 27416027 4 20 theme expanded 621:628 arg1 proteins 644:651 proteins 644:651 proteins involved in carbohydrate metabolism 644:687 This can be illustrated by the presence of a highly expanded repertoire of proteins involved in carbohydrate metabolism, in phase with the large diversity of polysaccharides originating from the diet or from the host itself that can be encountered in this environment. 27416027 4 20 theme expanded 621:628 arg1 repertoire 630:639 a highly expanded repertoire 612:639 a highly expanded repertoire of proteins involved in carbohydrate metabolism 612:687 This can be illustrated by the presence of a highly expanded repertoire of proteins involved in carbohydrate metabolism, in phase with the large diversity of polysaccharides originating from the diet or from the host itself that can be encountered in this environment. 27416027 5 21 theme non-gut 1049:1055 arg1 relatives 1057:1065 their close non-gut relatives 1037:1065 their close non-gut relatives 1037:1065 In order to identify other bacterial functions that are important in the human gut environment, we investigated the distribution of functional groups of proteins in a group of human gut bacteria and their close non-gut relatives. 27416027 0 22 theme Gut 186:188 arg1 Environment 190:200 the Gut Environment 182:200 the Gut Environment 182:200 Functional Comparison of Bacteria from the Human Gut and Closely Related Non-Gut Bacteria Reveals the Importance of Conjugation and a Paucity of Motility and Chemotaxis Functions in the Gut Environment. 27416027 0 23 theme Functional 0:9 arg1 Comparison 11:20 Functional Comparison 0:20 Functional Comparison of Bacteria from the Human Gut and Closely Related Non-Gut Bacteria 0:88 Functional Comparison of Bacteria from the Human Gut and Closely Related Non-Gut Bacteria Reveals the Importance of Conjugation and a Paucity of Motility and Chemotaxis Functions in the Gut Environment. 27416027 2 24 theme symbiotic 437:445 arg1 relationships 447:459 symbiotic relationships 437:459 symbiotic relationships 437:459 The gut microbiota is shaped by millennia of evolution to co-exist with the host in commensal or symbiotic relationships. 27416027 6 25 theme functions 1198:1206 arg1 functions 1198:1206 functions 1198:1206 functions directly related to the gut environment 1198:1246 Complementary to earlier global comparisons between different ecosystems, this approach should allow a closer focus on a group of functions directly related to the gut environment while avoiding functions related to taxonomically divergent microbiota composition, which may or may not be relevant for gut homeostasis. 27416027 6 25 theme functions 1198:1206 arg1 group 1189:1193 a group 1187:1193 a group of functions directly related to the gut environment 1187:1246 Complementary to earlier global comparisons between different ecosystems, this approach should allow a closer focus on a group of functions directly related to the gut environment while avoiding functions related to taxonomically divergent microbiota composition, which may or may not be relevant for gut homeostasis. 27416027 6 26 theme different 1120:1128 arg1 ecosystems 1130:1139 different ecosystems 1120:1139 different ecosystems 1120:1139 Complementary to earlier global comparisons between different ecosystems, this approach should allow a closer focus on a group of functions directly related to the gut environment while avoiding functions related to taxonomically divergent microbiota composition, which may or may not be relevant for gut homeostasis. 27416027 1 27 theme microbial 308:316 arg1 communities 318:328 the densest microbial communities 296:328 the densest microbial communities on earth 296:337 The human GI tract is a complex and still poorly understood environment, inhabited by one of the densest microbial communities on earth. 27416027 6 28 theme earlier 1085:1091 arg1 comparisons 1100:1110 earlier global comparisons 1085:1110 earlier global comparisons between different ecosystems 1085:1139 Complementary to earlier global comparisons between different ecosystems, this approach should allow a closer focus on a group of functions directly related to the gut environment while avoiding functions related to taxonomically divergent microbiota composition, which may or may not be relevant for gut homeostasis. 27416027 7 29 theme gut 1456:1458 arg1 bacteria 1460:1467 the human gut bacteria 1446:1467 the human gut bacteria which had not been recognized in a global approach 1446:1518 We identified several functions that are overrepresented in the human gut bacteria which had not been recognized in a global approach. 27416027 3 30 theme human 546:550 arg1 environment 556:566 the human gut environment 542:566 the human gut environment 542:566 Members of the gut microbiota perform specific molecular functions important in the human gut environment. 27416027 2 31 theme gut 344:346 arg1 microbiota 348:357 The gut microbiota 340:357 The gut microbiota 340:357 The gut microbiota is shaped by millennia of evolution to co-exist with the host in commensal or symbiotic relationships. 27416027 0 32 theme Bacteria 25:32 arg1 Comparison 11:20 Functional Comparison 0:20 Functional Comparison of Bacteria from the Human Gut and Closely Related Non-Gut Bacteria 0:88 Functional Comparison of Bacteria from the Human Gut and Closely Related Non-Gut Bacteria Reveals the Importance of Conjugation and a Paucity of Motility and Chemotaxis Functions in the Gut Environment. 27416027 1 33 theme understood 252:261 arg1 environment 263:273 a complex and still poorly understood environment 225:273 a complex and still poorly understood environment 225:273 The human GI tract is a complex and still poorly understood environment, inhabited by one of the densest microbial communities on earth. 27416027 1 33 theme understood 252:261 arg1 tract 216:220 The human GI tract 203:220 The human GI tract 203:220 The human GI tract is a complex and still poorly understood environment, inhabited by one of the densest microbial communities on earth. 27416027 0 34 theme Conjugation 116:126 arg1 Paucity 134:140 a Paucity 132:140 a Paucity of Motility and Chemotaxis Functions 132:177 Functional Comparison of Bacteria from the Human Gut and Closely Related Non-Gut Bacteria Reveals the Importance of Conjugation and a Paucity of Motility and Chemotaxis Functions in the Gut Environment. 27416027 0 34 theme Conjugation 116:126 arg1 Importance 102:111 the Importance 98:111 the Importance of Conjugation 98:126 Functional Comparison of Bacteria from the Human Gut and Closely Related Non-Gut Bacteria Reveals the Importance of Conjugation and a Paucity of Motility and Chemotaxis Functions in the Gut Environment. 27416027 6 35 theme global 1093:1098 arg1 comparisons 1100:1110 earlier global comparisons 1085:1110 earlier global comparisons between different ecosystems 1085:1139 Complementary to earlier global comparisons between different ecosystems, this approach should allow a closer focus on a group of functions directly related to the gut environment while avoiding functions related to taxonomically divergent microbiota composition, which may or may not be relevant for gut homeostasis. 27416027 3 36 theme important 529:537 arg1 functions 519:527 specific molecular functions 500:527 specific molecular functions important in the human gut environment 500:566 Members of the gut microbiota perform specific molecular functions important in the human gut environment. 27416027 3 37 from environment 556:566 arg1 important 529:537 important 529:537 important 529:537 Members of the gut microbiota perform specific molecular functions important in the human gut environment. 27416027 2 38 theme evolution 385:393 arg1 millennia 372:380 millennia 372:380 millennia of evolution to co-exist with the host in commensal or symbiotic relationships 372:459 The gut microbiota is shaped by millennia of evolution to co-exist with the host in commensal or symbiotic relationships. 27416027 6 39 theme divergent 1298:1306 arg1 composition 1319:1329 taxonomically divergent microbiota composition 1284:1329 taxonomically divergent microbiota composition 1284:1329 Complementary to earlier global comparisons between different ecosystems, this approach should allow a closer focus on a group of functions directly related to the gut environment while avoiding functions related to taxonomically divergent microbiota composition, which may or may not be relevant for gut homeostasis. 27416027 5 40 theme human 1014:1018 arg1 bacteria 1024:1031 human gut bacteria 1014:1031 human gut bacteria 1014:1031 In order to identify other bacterial functions that are important in the human gut environment, we investigated the distribution of functional groups of proteins in a group of human gut bacteria and their close non-gut relatives. 27416027 4 41 theme large 708:712 arg1 diversity 714:722 the large diversity 704:722 the large diversity of polysaccharides originating from the diet or from the host itself that can be encountered in this environment 704:835 This can be illustrated by the presence of a highly expanded repertoire of proteins involved in carbohydrate metabolism, in phase with the large diversity of polysaccharides originating from the diet or from the host itself that can be encountered in this environment. 27416027 5 42 theme gut 917:919 arg1 environment 921:931 the human gut environment 907:931 the human gut environment 907:931 In order to identify other bacterial functions that are important in the human gut environment, we investigated the distribution of functional groups of proteins in a group of human gut bacteria and their close non-gut relatives. 27416027 3 43 theme specific 500:507 arg1 functions 519:527 specific molecular functions 500:527 specific molecular functions important in the human gut environment 500:566 Members of the gut microbiota perform specific molecular functions important in the human gut environment. 27416027 5 44 theme functional 970:979 arg1 groups 981:986 functional groups 970:986 functional groups of proteins 970:998 In order to identify other bacterial functions that are important in the human gut environment, we investigated the distribution of functional groups of proteins in a group of human gut bacteria and their close non-gut relatives. 27416027 5 44 theme functional 970:979 arg1 proteins 991:998 proteins 991:998 proteins 991:998 In order to identify other bacterial functions that are important in the human gut environment, we investigated the distribution of functional groups of proteins in a group of human gut bacteria and their close non-gut relatives. 27416027 4 45 theme repertoire 630:639 arg1 presence 600:607 the presence 596:607 the presence of a highly expanded repertoire of proteins involved in carbohydrate metabolism 596:687 This can be illustrated by the presence of a highly expanded repertoire of proteins involved in carbohydrate metabolism, in phase with the large diversity of polysaccharides originating from the diet or from the host itself that can be encountered in this environment. 27416027 1 46 from communities 318:328 arg1 earth 333:337 earth 333:337 earth 333:337 The human GI tract is a complex and still poorly understood environment, inhabited by one of the densest microbial communities on earth. 27416027 6 47 theme gut 1369:1371 arg1 homeostasis 1373:1383 gut homeostasis 1369:1383 gut homeostasis 1369:1383 Complementary to earlier global comparisons between different ecosystems, this approach should allow a closer focus on a group of functions directly related to the gut environment while avoiding functions related to taxonomically divergent microbiota composition, which may or may not be relevant for gut homeostasis. 27416027 5 48 theme bacteria 1024:1031 arg1 group 1005:1009 a group 1003:1009 a group of human gut bacteria and their close non-gut relatives 1003:1065 In order to identify other bacterial functions that are important in the human gut environment, we investigated the distribution of functional groups of proteins in a group of human gut bacteria and their close non-gut relatives. 27416027 5 48 theme bacteria 1024:1031 arg1 relatives 1057:1065 their close non-gut relatives 1037:1065 their close non-gut relatives 1037:1065 In order to identify other bacterial functions that are important in the human gut environment, we investigated the distribution of functional groups of proteins in a group of human gut bacteria and their close non-gut relatives. 27416027 5 48 theme bacteria 1024:1031 arg1 bacteria 1024:1031 human gut bacteria 1014:1031 human gut bacteria 1014:1031 In order to identify other bacterial functions that are important in the human gut environment, we investigated the distribution of functional groups of proteins in a group of human gut bacteria and their close non-gut relatives. 27416027 5 49 theme groups 981:986 arg1 distribution 954:965 the distribution 950:965 the distribution of functional groups of proteins in a group of human gut bacteria and their close non-gut relatives 950:1065 In order to identify other bacterial functions that are important in the human gut environment, we investigated the distribution of functional groups of proteins in a group of human gut bacteria and their close non-gut relatives. 27416027 8 50 theme observed 1525:1532 arg1 under-representation 1534:1553 The observed under-representation 1521:1553 The observed under-representation of certain other functions 1521:1580 The observed under-representation of certain other functions may be equally important for gut homeostasis. 27416027 8 50 theme observed 1525:1532 arg1 important 1597:1605 important 1597:1605 important 1597:1605 The observed under-representation of certain other functions may be equally important for gut homeostasis. 27416027 6 51 theme related 1273:1279 arg1 functions 1263:1271 functions 1263:1271 functions related to taxonomically divergent microbiota composition, which may or may not be relevant for gut homeostasis 1263:1383 Complementary to earlier global comparisons between different ecosystems, this approach should allow a closer focus on a group of functions directly related to the gut environment while avoiding functions related to taxonomically divergent microbiota composition, which may or may not be relevant for gut homeostasis. 27416027 3 52 theme gut 552:554 arg1 environment 556:566 the human gut environment 542:566 the human gut environment 542:566 Members of the gut microbiota perform specific molecular functions important in the human gut environment. 27416027 5 53 theme bacterial 865:873 arg1 functions 875:883 other bacterial functions 859:883 other bacterial functions that are important in the human gut environment 859:931 In order to identify other bacterial functions that are important in the human gut environment, we investigated the distribution of functional groups of proteins in a group of human gut bacteria and their close non-gut relatives. 27416027 0 54 theme Human 43:47 arg1 Gut 49:51 the Human Gut 39:51 the Human Gut 39:51 Functional Comparison of Bacteria from the Human Gut and Closely Related Non-Gut Bacteria Reveals the Importance of Conjugation and a Paucity of Motility and Chemotaxis Functions in the Gut Environment. 27416027 8 55 theme certain 1558:1564 arg1 functions 1572:1580 certain other functions 1558:1580 certain other functions 1558:1580 The observed under-representation of certain other functions may be equally important for gut homeostasis. 27416027 6 56 theme microbiota 1308:1317 arg1 composition 1319:1329 taxonomically divergent microbiota composition 1284:1329 taxonomically divergent microbiota composition 1284:1329 Complementary to earlier global comparisons between different ecosystems, this approach should allow a closer focus on a group of functions directly related to the gut environment while avoiding functions related to taxonomically divergent microbiota composition, which may or may not be relevant for gut homeostasis. 27416027 5 57 theme proteins 991:998 arg1 groups 981:986 functional groups 970:986 functional groups of proteins 970:998 In order to identify other bacterial functions that are important in the human gut environment, we investigated the distribution of functional groups of proteins in a group of human gut bacteria and their close non-gut relatives. 27416027 5 57 theme proteins 991:998 arg1 proteins 991:998 proteins 991:998 proteins 991:998 In order to identify other bacterial functions that are important in the human gut environment, we investigated the distribution of functional groups of proteins in a group of human gut bacteria and their close non-gut relatives. 27416027 0 58 dep Motility 145:152 arg1 Functions 169:177 Functions 169:177 Functions 169:177 Functional Comparison of Bacteria from the Human Gut and Closely Related Non-Gut Bacteria Reveals the Importance of Conjugation and a Paucity of Motility and Chemotaxis Functions in the Gut Environment. 27416027 3 59 from important 529:537 arg1 environment 556:566 the human gut environment 542:566 the human gut environment 542:566 Members of the gut microbiota perform specific molecular functions important in the human gut environment. 27416027 6 60 theme gut 1232:1234 arg1 environment 1236:1246 the gut environment 1228:1246 the gut environment 1228:1246 Complementary to earlier global comparisons between different ecosystems, this approach should allow a closer focus on a group of functions directly related to the gut environment while avoiding functions related to taxonomically divergent microbiota composition, which may or may not be relevant for gut homeostasis. 27416027 6 61 theme closer 1171:1176 arg1 focus 1178:1182 a closer focus 1169:1182 a closer focus on a group of functions directly related to the gut environment 1169:1246 Complementary to earlier global comparisons between different ecosystems, this approach should allow a closer focus on a group of functions directly related to the gut environment while avoiding functions related to taxonomically divergent microbiota composition, which may or may not be relevant for gut homeostasis. 27416027 8 62 theme functions 1572:1580 arg1 under-representation 1534:1553 The observed under-representation 1521:1553 The observed under-representation of certain other functions 1521:1580 The observed under-representation of certain other functions may be equally important for gut homeostasis. 27416027 8 62 theme functions 1572:1580 arg1 important 1597:1605 important 1597:1605 important 1597:1605 The observed under-representation of certain other functions may be equally important for gut homeostasis. 27416027 6 63 from focus 1178:1182 arg1 functions 1198:1206 functions 1198:1206 functions directly related to the gut environment 1198:1246 Complementary to earlier global comparisons between different ecosystems, this approach should allow a closer focus on a group of functions directly related to the gut environment while avoiding functions related to taxonomically divergent microbiota composition, which may or may not be relevant for gut homeostasis. 27416027 6 63 from focus 1178:1182 arg1 group 1189:1193 a group 1187:1193 a group of functions directly related to the gut environment 1187:1246 Complementary to earlier global comparisons between different ecosystems, this approach should allow a closer focus on a group of functions directly related to the gut environment while avoiding functions related to taxonomically divergent microbiota composition, which may or may not be relevant for gut homeostasis. 27416027 1 64 theme human 207:211 arg1 tract 216:220 The human GI tract 203:220 The human GI tract 203:220 The human GI tract is a complex and still poorly understood environment, inhabited by one of the densest microbial communities on earth. 27416027 1 64 theme human 207:211 arg1 environment 263:273 a complex and still poorly understood environment 225:273 a complex and still poorly understood environment 225:273 The human GI tract is a complex and still poorly understood environment, inhabited by one of the densest microbial communities on earth. 27416027 0 65 theme Motility 145:152 arg1 Paucity 134:140 a Paucity 132:140 a Paucity of Motility and Chemotaxis Functions 132:177 Functional Comparison of Bacteria from the Human Gut and Closely Related Non-Gut Bacteria Reveals the Importance of Conjugation and a Paucity of Motility and Chemotaxis Functions in the Gut Environment. 27416027 0 65 theme Motility 145:152 arg1 Importance 102:111 the Importance 98:111 the Importance of Conjugation 98:126 Functional Comparison of Bacteria from the Human Gut and Closely Related Non-Gut Bacteria Reveals the Importance of Conjugation and a Paucity of Motility and Chemotaxis Functions in the Gut Environment. 27416027 4 66 theme polysaccharides 727:741 arg1 diversity 714:722 the large diversity 704:722 the large diversity of polysaccharides originating from the diet or from the host itself that can be encountered in this environment 704:835 This can be illustrated by the presence of a highly expanded repertoire of proteins involved in carbohydrate metabolism, in phase with the large diversity of polysaccharides originating from the diet or from the host itself that can be encountered in this environment. 27416027 5 67 theme gut 1020:1022 arg1 bacteria 1024:1031 human gut bacteria 1014:1031 human gut bacteria 1014:1031 In order to identify other bacterial functions that are important in the human gut environment, we investigated the distribution of functional groups of proteins in a group of human gut bacteria and their close non-gut relatives. 27416027 4 68 theme proteins 644:651 arg1 proteins 644:651 proteins 644:651 proteins involved in carbohydrate metabolism 644:687 This can be illustrated by the presence of a highly expanded repertoire of proteins involved in carbohydrate metabolism, in phase with the large diversity of polysaccharides originating from the diet or from the host itself that can be encountered in this environment. 27416027 4 68 theme proteins 644:651 arg1 repertoire 630:639 a highly expanded repertoire 612:639 a highly expanded repertoire of proteins involved in carbohydrate metabolism 612:687 This can be illustrated by the presence of a highly expanded repertoire of proteins involved in carbohydrate metabolism, in phase with the large diversity of polysaccharides originating from the diet or from the host itself that can be encountered in this environment. 27416027 5 69 from important 894:902 arg1 environment 921:931 the human gut environment 907:931 the human gut environment 907:931 In order to identify other bacterial functions that are important in the human gut environment, we investigated the distribution of functional groups of proteins in a group of human gut bacteria and their close non-gut relatives. 27416027 1 70 theme GI 213:214 arg1 tract 216:220 The human GI tract 203:220 The human GI tract 203:220 The human GI tract is a complex and still poorly understood environment, inhabited by one of the densest microbial communities on earth. 27416027 1 70 theme GI 213:214 arg1 environment 263:273 a complex and still poorly understood environment 225:273 a complex and still poorly understood environment 225:273 The human GI tract is a complex and still poorly understood environment, inhabited by one of the densest microbial communities on earth. 27416027 5 71 from environment 921:931 arg1 important 894:902 important 894:902 important 894:902 In order to identify other bacterial functions that are important in the human gut environment, we investigated the distribution of functional groups of proteins in a group of human gut bacteria and their close non-gut relatives. 27416027 3 72 theme gut 477:479 arg1 microbiota 481:490 the gut microbiota 473:490 the gut microbiota 473:490 Members of the gut microbiota perform specific molecular functions important in the human gut environment. 27416027 8 73 theme gut 1611:1613 arg1 homeostasis 1615:1625 gut homeostasis 1611:1625 gut homeostasis 1611:1625 The observed under-representation of certain other functions may be equally important for gut homeostasis. 27416027 4 74 with phase 693:697 arg1 diversity 714:722 the large diversity 704:722 the large diversity of polysaccharides originating from the diet or from the host itself that can be encountered in this environment 704:835 This can be illustrated by the presence of a highly expanded repertoire of proteins involved in carbohydrate metabolism, in phase with the large diversity of polysaccharides originating from the diet or from the host itself that can be encountered in this environment. 27416027 8 75 theme other 1566:1570 arg1 functions 1572:1580 certain other functions 1558:1580 certain other functions 1558:1580 The observed under-representation of certain other functions may be equally important for gut homeostasis. 27416027 3 76 theme microbiota 481:490 arg1 Members 462:468 Members 462:468 Members of the gut microbiota 462:490 Members of the gut microbiota perform specific molecular functions important in the human gut environment. 27416027 9 77 theme new 1669:1671 arg1 information 1673:1683 new information 1669:1683 new information about this environment 1669:1706 Together, these analyses provide us with new information about this environment so critical to our health and well-being. 26428239 3 0 theme microbial 525:533 arg1 adhesion 535:542 the microbial adhesion 521:542 the microbial adhesion to hydrocarbons (MATH) assay and contact angle measurements 521:602 To elucidate the mechanism of the aggregative behaviour, the microbial adhesion to hydrocarbons (MATH) assay and contact angle measurements were performed that pointed to an increased cell surface hydrophobicity. 26428239 0 1 from regulation 8:17 arg1 taiwanensis 53:63 Pseudomonas taiwanensis VLB120 41:70 Pseudomonas taiwanensis VLB120 41:70 Trophic regulation of autoaggregation in Pseudomonas taiwanensis VLB120. 26428239 4 2 from lipopolysaccharide 805:822 arg1 amount 761:766 a reduced amount 751:766 a reduced amount of O-specific polysaccharides in the lipopolysaccharide of the mutant cells 751:842 Moreover, investigations of the outer layer of the cell membrane revealed a reduced amount of O-specific polysaccharides in the lipopolysaccharide of the mutant cells. 26428239 4 2 from lipopolysaccharide 805:822 arg1 polysaccharides 782:796 O-specific polysaccharides 771:796 O-specific polysaccharides in the lipopolysaccharide of the mutant cells 771:842 Moreover, investigations of the outer layer of the cell membrane revealed a reduced amount of O-specific polysaccharides in the lipopolysaccharide of the mutant cells. 26428239 1 3 theme organic 273:279 arg1 acids 281:285 organic acids 273:285 organic acids 273:285 Five mutants of Pseudomonas taiwanensis VLB120ΔCeGFP showed significant autoaggregation when growing on defined carbohydrates or gluconate, while they grew as suspended cells on complex medium and on organic acids like citrate and succinate. 26428239 6 4 theme diguanylate 1307:1317 arg1 concentration 1319:1331 the cellular cyclic diguanylate concentration 1287:1331 the cellular cyclic diguanylate concentration 1287:1331 In summary, it appears that the trophic autoaggregation was regulated via cyclic diguanylate and a link between the cellular cyclic diguanylate concentration and the lipopolysaccharide composition of P. taiwanensis VLB120ΔCeGFP is suggested. 26428239 6 5 theme trophic 1207:1213 arg1 autoaggregation 1215:1229 the trophic autoaggregation 1203:1229 the trophic autoaggregation 1203:1229 In summary, it appears that the trophic autoaggregation was regulated via cyclic diguanylate and a link between the cellular cyclic diguanylate concentration and the lipopolysaccharide composition of P. taiwanensis VLB120ΔCeGFP is suggested. 26428239 2 6 theme respective 333:342 arg1 mutations 344:352 the respective mutations 329:352 the respective mutations 329:352 Surprisingly, the respective mutations affected very different genes, although all five strains exhibited the same behaviour of aggregate formation. 26428239 6 7 theme cyclic 1300:1305 arg1 concentration 1319:1331 the cellular cyclic diguanylate concentration 1287:1331 the cellular cyclic diguanylate concentration 1287:1331 In summary, it appears that the trophic autoaggregation was regulated via cyclic diguanylate and a link between the cellular cyclic diguanylate concentration and the lipopolysaccharide composition of P. taiwanensis VLB120ΔCeGFP is suggested. 26428239 4 8 theme polysaccharides 782:796 arg1 amount 761:766 a reduced amount 751:766 a reduced amount of O-specific polysaccharides in the lipopolysaccharide of the mutant cells 751:842 Moreover, investigations of the outer layer of the cell membrane revealed a reduced amount of O-specific polysaccharides in the lipopolysaccharide of the mutant cells. 26428239 4 8 theme polysaccharides 782:796 arg1 polysaccharides 782:796 O-specific polysaccharides 771:796 O-specific polysaccharides in the lipopolysaccharide of the mutant cells 771:842 Moreover, investigations of the outer layer of the cell membrane revealed a reduced amount of O-specific polysaccharides in the lipopolysaccharide of the mutant cells. 26428239 3 9 theme behaviour 510:518 arg1 mechanism 481:489 the mechanism 477:489 the mechanism of the aggregative behaviour 477:518 To elucidate the mechanism of the aggregative behaviour, the microbial adhesion to hydrocarbons (MATH) assay and contact angle measurements were performed that pointed to an increased cell surface hydrophobicity. 26428239 1 10 theme significant 133:143 arg1 autoaggregation 145:159 significant autoaggregation 133:159 significant autoaggregation when growing on defined carbohydrates or gluconate 133:210 Five mutants of Pseudomonas taiwanensis VLB120ΔCeGFP showed significant autoaggregation when growing on defined carbohydrates or gluconate, while they grew as suspended cells on complex medium and on organic acids like citrate and succinate. 26428239 6 11 theme cellular 1291:1298 arg1 concentration 1319:1331 the cellular cyclic diguanylate concentration 1287:1331 the cellular cyclic diguanylate concentration 1287:1331 In summary, it appears that the trophic autoaggregation was regulated via cyclic diguanylate and a link between the cellular cyclic diguanylate concentration and the lipopolysaccharide composition of P. taiwanensis VLB120ΔCeGFP is suggested. 26428239 4 12 from polysaccharides 782:796 arg1 lipopolysaccharide 805:822 the lipopolysaccharide 801:822 the lipopolysaccharide of the mutant cells 801:842 Moreover, investigations of the outer layer of the cell membrane revealed a reduced amount of O-specific polysaccharides in the lipopolysaccharide of the mutant cells. 26428239 5 13 theme gene 1014:1017 arg1 transcription 995:1007 the transcription 991:1007 the transcription 991:1007 To determine the regulation of the aggregation, reverse transcription quantitative real-time PCR was performed and, irrespective of the mutation, the transcription of a gene encoding a putative phosphodiesterase, which is degrading the global second messenger cyclic diguanylate, was decreased or even deactivated in all mutants. 26428239 5 14 theme reverse 893:899 arg1 PCR 938:940 reverse transcription quantitative real-time PCR 893:940 reverse transcription quantitative real-time PCR 893:940 To determine the regulation of the aggregation, reverse transcription quantitative real-time PCR was performed and, irrespective of the mutation, the transcription of a gene encoding a putative phosphodiesterase, which is degrading the global second messenger cyclic diguanylate, was decreased or even deactivated in all mutants. 26428239 5 15 theme putative 1030:1037 arg1 phosphodiesterase 1039:1055 a putative phosphodiesterase 1028:1055 a putative phosphodiesterase 1028:1055 To determine the regulation of the aggregation, reverse transcription quantitative real-time PCR was performed and, irrespective of the mutation, the transcription of a gene encoding a putative phosphodiesterase, which is degrading the global second messenger cyclic diguanylate, was decreased or even deactivated in all mutants. 26428239 1 16 theme Pseudomonas 89:99 arg1 VLB120ΔCeGFP 113:124 Pseudomonas taiwanensis VLB120ΔCeGFP 89:124 Pseudomonas taiwanensis VLB120ΔCeGFP 89:124 Five mutants of Pseudomonas taiwanensis VLB120ΔCeGFP showed significant autoaggregation when growing on defined carbohydrates or gluconate, while they grew as suspended cells on complex medium and on organic acids like citrate and succinate. 26428239 5 17 theme transcription 901:913 arg1 PCR 938:940 reverse transcription quantitative real-time PCR 893:940 reverse transcription quantitative real-time PCR 893:940 To determine the regulation of the aggregation, reverse transcription quantitative real-time PCR was performed and, irrespective of the mutation, the transcription of a gene encoding a putative phosphodiesterase, which is degrading the global second messenger cyclic diguanylate, was decreased or even deactivated in all mutants. 26428239 0 18 theme Trophic 0:6 arg1 regulation 8:17 Trophic regulation 0:17 Trophic regulation of autoaggregation in Pseudomonas taiwanensis VLB120. 0:71 Trophic regulation of autoaggregation in Pseudomonas taiwanensis VLB120. 26428239 4 19 from amount 761:766 arg1 lipopolysaccharide 805:822 the lipopolysaccharide 801:822 the lipopolysaccharide of the mutant cells 801:842 Moreover, investigations of the outer layer of the cell membrane revealed a reduced amount of O-specific polysaccharides in the lipopolysaccharide of the mutant cells. 26428239 1 20 theme taiwanensis 101:111 arg1 VLB120ΔCeGFP 113:124 Pseudomonas taiwanensis VLB120ΔCeGFP 89:124 Pseudomonas taiwanensis VLB120ΔCeGFP 89:124 Five mutants of Pseudomonas taiwanensis VLB120ΔCeGFP showed significant autoaggregation when growing on defined carbohydrates or gluconate, while they grew as suspended cells on complex medium and on organic acids like citrate and succinate. 26428239 5 21 theme quantitative 915:926 arg1 PCR 938:940 reverse transcription quantitative real-time PCR 893:940 reverse transcription quantitative real-time PCR 893:940 To determine the regulation of the aggregation, reverse transcription quantitative real-time PCR was performed and, irrespective of the mutation, the transcription of a gene encoding a putative phosphodiesterase, which is degrading the global second messenger cyclic diguanylate, was decreased or even deactivated in all mutants. 26428239 0 22 theme autoaggregation 22:36 arg1 regulation 8:17 Trophic regulation 0:17 Trophic regulation of autoaggregation in Pseudomonas taiwanensis VLB120. 0:71 Trophic regulation of autoaggregation in Pseudomonas taiwanensis VLB120. 26428239 4 23 theme reduced 753:759 arg1 amount 761:766 a reduced amount 751:766 a reduced amount of O-specific polysaccharides in the lipopolysaccharide of the mutant cells 751:842 Moreover, investigations of the outer layer of the cell membrane revealed a reduced amount of O-specific polysaccharides in the lipopolysaccharide of the mutant cells. 26428239 4 23 theme reduced 753:759 arg1 polysaccharides 782:796 O-specific polysaccharides 771:796 O-specific polysaccharides in the lipopolysaccharide of the mutant cells 771:842 Moreover, investigations of the outer layer of the cell membrane revealed a reduced amount of O-specific polysaccharides in the lipopolysaccharide of the mutant cells. 26428239 1 24 theme VLB120ΔCeGFP 113:124 arg1 mutants 78:84 Five mutants 73:84 Five mutants of Pseudomonas taiwanensis VLB120ΔCeGFP 73:124 Five mutants of Pseudomonas taiwanensis VLB120ΔCeGFP showed significant autoaggregation when growing on defined carbohydrates or gluconate, while they grew as suspended cells on complex medium and on organic acids like citrate and succinate. 26428239 2 25 theme aggregate 443:451 arg1 formation 453:461 aggregate formation 443:461 aggregate formation 443:461 Surprisingly, the respective mutations affected very different genes, although all five strains exhibited the same behaviour of aggregate formation. 26428239 2 26 theme formation 453:461 arg1 behaviour 430:438 the same behaviour 421:438 the same behaviour of aggregate formation 421:461 Surprisingly, the respective mutations affected very different genes, although all five strains exhibited the same behaviour of aggregate formation. 26428239 6 27 theme VLB120ΔCeGFP 1390:1401 arg1 composition 1360:1370 the lipopolysaccharide composition 1337:1370 the lipopolysaccharide composition of P. taiwanensis VLB120ΔCeGFP 1337:1401 In summary, it appears that the trophic autoaggregation was regulated via cyclic diguanylate and a link between the cellular cyclic diguanylate concentration and the lipopolysaccharide composition of P. taiwanensis VLB120ΔCeGFP is suggested. 26428239 6 27 theme VLB120ΔCeGFP 1390:1401 arg1 concentration 1319:1331 the cellular cyclic diguanylate concentration 1287:1331 the cellular cyclic diguanylate concentration 1287:1331 In summary, it appears that the trophic autoaggregation was regulated via cyclic diguanylate and a link between the cellular cyclic diguanylate concentration and the lipopolysaccharide composition of P. taiwanensis VLB120ΔCeGFP is suggested. 26428239 5 28 theme cyclic 1105:1110 arg1 diguanylate 1112:1122 the global second messenger cyclic diguanylate 1077:1122 the global second messenger cyclic diguanylate 1077:1122 To determine the regulation of the aggregation, reverse transcription quantitative real-time PCR was performed and, irrespective of the mutation, the transcription of a gene encoding a putative phosphodiesterase, which is degrading the global second messenger cyclic diguanylate, was decreased or even deactivated in all mutants. 26428239 3 29 theme contact 577:583 arg1 measurements 591:602 contact angle measurements 577:602 contact angle measurements 577:602 To elucidate the mechanism of the aggregative behaviour, the microbial adhesion to hydrocarbons (MATH) assay and contact angle measurements were performed that pointed to an increased cell surface hydrophobicity. 26428239 5 30 theme real-time 928:936 arg1 PCR 938:940 reverse transcription quantitative real-time PCR 893:940 reverse transcription quantitative real-time PCR 893:940 To determine the regulation of the aggregation, reverse transcription quantitative real-time PCR was performed and, irrespective of the mutation, the transcription of a gene encoding a putative phosphodiesterase, which is degrading the global second messenger cyclic diguanylate, was decreased or even deactivated in all mutants. 26428239 0 31 theme Pseudomonas 41:51 arg1 taiwanensis 53:63 Pseudomonas taiwanensis VLB120 41:70 Pseudomonas taiwanensis VLB120 41:70 Trophic regulation of autoaggregation in Pseudomonas taiwanensis VLB120. 26428239 6 32 theme taiwanensis 1378:1388 arg1 VLB120ΔCeGFP 1390:1401 P. taiwanensis VLB120ΔCeGFP 1375:1401 P. taiwanensis VLB120ΔCeGFP 1375:1401 In summary, it appears that the trophic autoaggregation was regulated via cyclic diguanylate and a link between the cellular cyclic diguanylate concentration and the lipopolysaccharide composition of P. taiwanensis VLB120ΔCeGFP is suggested. 26428239 1 33 theme suspended 232:240 arg1 cells 242:246 suspended cells 232:246 suspended cells 232:246 Five mutants of Pseudomonas taiwanensis VLB120ΔCeGFP showed significant autoaggregation when growing on defined carbohydrates or gluconate, while they grew as suspended cells on complex medium and on organic acids like citrate and succinate. 26428239 6 34 theme P. 1375:1376 arg1 VLB120ΔCeGFP 1390:1401 P. taiwanensis VLB120ΔCeGFP 1375:1401 P. taiwanensis VLB120ΔCeGFP 1375:1401 In summary, it appears that the trophic autoaggregation was regulated via cyclic diguanylate and a link between the cellular cyclic diguanylate concentration and the lipopolysaccharide composition of P. taiwanensis VLB120ΔCeGFP is suggested. 26428239 3 35 theme surface 653:659 arg1 hydrophobicity 661:674 an increased cell surface hydrophobicity 635:674 an increased cell surface hydrophobicity 635:674 To elucidate the mechanism of the aggregative behaviour, the microbial adhesion to hydrocarbons (MATH) assay and contact angle measurements were performed that pointed to an increased cell surface hydrophobicity. 26428239 5 36 theme aggregation 880:890 arg1 regulation 862:871 the regulation 858:871 the regulation of the aggregation 858:890 To determine the regulation of the aggregation, reverse transcription quantitative real-time PCR was performed and, irrespective of the mutation, the transcription of a gene encoding a putative phosphodiesterase, which is degrading the global second messenger cyclic diguanylate, was decreased or even deactivated in all mutants. 26428239 2 37 theme same 425:428 arg1 behaviour 430:438 the same behaviour 421:438 the same behaviour of aggregate formation 421:461 Surprisingly, the respective mutations affected very different genes, although all five strains exhibited the same behaviour of aggregate formation. 26428239 6 38 theme lipopolysaccharide 1341:1358 arg1 composition 1360:1370 the lipopolysaccharide composition 1337:1370 the lipopolysaccharide composition of P. taiwanensis VLB120ΔCeGFP 1337:1401 In summary, it appears that the trophic autoaggregation was regulated via cyclic diguanylate and a link between the cellular cyclic diguanylate concentration and the lipopolysaccharide composition of P. taiwanensis VLB120ΔCeGFP is suggested. 26428239 2 39 theme different 368:376 arg1 genes 378:382 very different genes 363:382 very different genes 363:382 Surprisingly, the respective mutations affected very different genes, although all five strains exhibited the same behaviour of aggregate formation. 26428239 6 40 theme cyclic 1249:1254 arg1 diguanylate 1256:1266 cyclic diguanylate 1249:1266 cyclic diguanylate 1249:1266 In summary, it appears that the trophic autoaggregation was regulated via cyclic diguanylate and a link between the cellular cyclic diguanylate concentration and the lipopolysaccharide composition of P. taiwanensis VLB120ΔCeGFP is suggested. 26428239 4 41 theme cell 728:731 arg1 membrane 733:740 the cell membrane 724:740 the cell membrane 724:740 Moreover, investigations of the outer layer of the cell membrane revealed a reduced amount of O-specific polysaccharides in the lipopolysaccharide of the mutant cells. 26428239 3 42 theme angle 585:589 arg1 measurements 591:602 contact angle measurements 577:602 contact angle measurements 577:602 To elucidate the mechanism of the aggregative behaviour, the microbial adhesion to hydrocarbons (MATH) assay and contact angle measurements were performed that pointed to an increased cell surface hydrophobicity. 26428239 4 43 theme membrane 733:740 arg1 layer 715:719 the outer layer 705:719 the outer layer of the cell membrane 705:740 Moreover, investigations of the outer layer of the cell membrane revealed a reduced amount of O-specific polysaccharides in the lipopolysaccharide of the mutant cells. 26428239 5 44 theme global 1081:1086 arg1 diguanylate 1112:1122 the global second messenger cyclic diguanylate 1077:1122 the global second messenger cyclic diguanylate 1077:1122 To determine the regulation of the aggregation, reverse transcription quantitative real-time PCR was performed and, irrespective of the mutation, the transcription of a gene encoding a putative phosphodiesterase, which is degrading the global second messenger cyclic diguanylate, was decreased or even deactivated in all mutants. 26428239 3 45 theme increased 638:646 arg1 hydrophobicity 661:674 an increased cell surface hydrophobicity 635:674 an increased cell surface hydrophobicity 635:674 To elucidate the mechanism of the aggregative behaviour, the microbial adhesion to hydrocarbons (MATH) assay and contact angle measurements were performed that pointed to an increased cell surface hydrophobicity. 26428239 4 46 theme outer 709:713 arg1 layer 715:719 the outer layer 705:719 the outer layer of the cell membrane 705:740 Moreover, investigations of the outer layer of the cell membrane revealed a reduced amount of O-specific polysaccharides in the lipopolysaccharide of the mutant cells. 26428239 3 47 theme aggregative 498:508 arg1 behaviour 510:518 the aggregative behaviour 494:518 the aggregative behaviour 494:518 To elucidate the mechanism of the aggregative behaviour, the microbial adhesion to hydrocarbons (MATH) assay and contact angle measurements were performed that pointed to an increased cell surface hydrophobicity. 26428239 4 48 theme O-specific 771:780 arg1 polysaccharides 782:796 O-specific polysaccharides 771:796 O-specific polysaccharides in the lipopolysaccharide of the mutant cells 771:842 Moreover, investigations of the outer layer of the cell membrane revealed a reduced amount of O-specific polysaccharides in the lipopolysaccharide of the mutant cells. 26428239 5 49 theme second 1088:1093 arg1 diguanylate 1112:1122 the global second messenger cyclic diguanylate 1077:1122 the global second messenger cyclic diguanylate 1077:1122 To determine the regulation of the aggregation, reverse transcription quantitative real-time PCR was performed and, irrespective of the mutation, the transcription of a gene encoding a putative phosphodiesterase, which is degrading the global second messenger cyclic diguanylate, was decreased or even deactivated in all mutants. 26428239 3 50 theme cell 648:651 arg1 hydrophobicity 661:674 an increased cell surface hydrophobicity 635:674 an increased cell surface hydrophobicity 635:674 To elucidate the mechanism of the aggregative behaviour, the microbial adhesion to hydrocarbons (MATH) assay and contact angle measurements were performed that pointed to an increased cell surface hydrophobicity. 26428239 1 51 theme defined 177:183 arg1 carbohydrates 185:197 defined carbohydrates 177:197 defined carbohydrates 177:197 Five mutants of Pseudomonas taiwanensis VLB120ΔCeGFP showed significant autoaggregation when growing on defined carbohydrates or gluconate, while they grew as suspended cells on complex medium and on organic acids like citrate and succinate. 26428239 1 52 theme complex 251:257 arg1 medium 259:264 complex medium 251:264 complex medium 251:264 Five mutants of Pseudomonas taiwanensis VLB120ΔCeGFP showed significant autoaggregation when growing on defined carbohydrates or gluconate, while they grew as suspended cells on complex medium and on organic acids like citrate and succinate. 26428239 5 53 theme messenger 1095:1103 arg1 diguanylate 1112:1122 the global second messenger cyclic diguanylate 1077:1122 the global second messenger cyclic diguanylate 1077:1122 To determine the regulation of the aggregation, reverse transcription quantitative real-time PCR was performed and, irrespective of the mutation, the transcription of a gene encoding a putative phosphodiesterase, which is degrading the global second messenger cyclic diguanylate, was decreased or even deactivated in all mutants. 26428239 4 54 theme cells 838:842 arg1 lipopolysaccharide 805:822 the lipopolysaccharide 801:822 the lipopolysaccharide of the mutant cells 801:842 Moreover, investigations of the outer layer of the cell membrane revealed a reduced amount of O-specific polysaccharides in the lipopolysaccharide of the mutant cells. 26428239 4 55 theme layer 715:719 arg1 investigations 687:700 investigations 687:700 investigations of the outer layer of the cell membrane 687:740 Moreover, investigations of the outer layer of the cell membrane revealed a reduced amount of O-specific polysaccharides in the lipopolysaccharide of the mutant cells. 26428239 4 56 theme mutant 831:836 arg1 cells 838:842 the mutant cells 827:842 the mutant cells 827:842 Moreover, investigations of the outer layer of the cell membrane revealed a reduced amount of O-specific polysaccharides in the lipopolysaccharide of the mutant cells. 26428239 3 57 theme hydrocarbons 547:558 arg1 assay 567:571 hydrocarbons (MATH) assay 547:571 hydrocarbons (MATH) assay 547:571 To elucidate the mechanism of the aggregative behaviour, the microbial adhesion to hydrocarbons (MATH) assay and contact angle measurements were performed that pointed to an increased cell surface hydrophobicity. 25147684 7 0 theme viruses 1012:1018 arg1 site 1000:1003 the cleavage site 987:1003 the cleavage site of all viruses 987:1018 Arg was in the cleavage site of all viruses and 11-12 N-linked glycosylation sites were found. 25147684 7 0 theme viruses 1012:1018 arg1 viruses 1012:1018 all viruses 1008:1018 all viruses 1008:1018 Arg was in the cleavage site of all viruses and 11-12 N-linked glycosylation sites were found. 25147684 10 1 link N-linked 1290:1297 arg1 glycosylation 1299:1311 N-linked glycosylation 1290:1311 N-linked glycosylation 1290:1311 At residue 146 of NA, there was N-linked glycosylation, and Ile-222 was found in the enzyme active site. 25147684 3 2 theme receptor-binding 397:412 arg1 sites 414:418 the cleavage and receptor-binding sites 380:418 sites 414:418 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 8 3 located found 1128:1132 arg1 PB2 1137:1139 PB2 1137:1139 PB2 of all viruses in this study 1137:1168 In NS1, Asp-92 and Ala-149 were detected and Lys-627 was found in PB2 of all viruses in this study. 25147684 8 3 located found 1128:1132 arg2 Lys-627 1116:1122 Lys-627 1116:1122 Lys-627 1116:1122 In NS1, Asp-92 and Ala-149 were detected and Lys-627 was found in PB2 of all viruses in this study. 25147684 4 4 theme virus 720:724 arg1 pathogenesis 726:737 the virus pathogenesis 716:737 the virus pathogenesis 716:737 OBJECTIVES The goal of this study was to find the alterations in genes, which might be responsible in the virus pathogenesis. 25147684 3 5 theme pathogenicity 578:590 arg1 substitutions 488:500 substitutions 488:500 substitutions in PB2, NS1 and M genes 488:524 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 3 5 theme pathogenicity 578:590 arg1 Binding 319:325 Binding 319:325 Binding of host proteases by the viral NA 319:359 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 3 5 theme pathogenicity 578:590 arg1 number 421:426 number 421:426 number of oligosaccharide side chains of HA 421:463 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 3 5 theme pathogenicity 578:590 arg1 shortening 466:475 shortening 466:475 shortening of NA 466:481 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 3 5 theme pathogenicity 578:590 arg1 sequence 362:369 sequence 362:369 sequence of HA in the cleavage and receptor-binding sites 362:418 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 3 5 theme pathogenicity 578:590 arg1 correlates 564:573 molecular correlates 554:573 molecular correlates of pathogenicity of influenza viruses 554:611 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 3 6 theme side 447:450 arg1 chains 452:457 oligosaccharide side chains 431:457 oligosaccharide side chains of HA 431:463 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 12 7 theme amino 1622:1626 arg1 level 1633:1637 the amino acid level 1618:1637 the amino acid level 1618:1637 It is important to mention that these changes were at the amino acid level and studies need to be performed on animals to investigate the significance of these findings. 25147684 1 8 theme A 146:146 arg1 PB2 197:199 PB2 197:199 PB2 197:199 BACKGROUND In the influenza A viruses, neuraminidase (NA), hemagglutinin (HA), PB2, NS1 and M are responsible for the disease pathogenicity. 25147684 1 8 theme A 146:146 arg1 hemagglutinin 177:189 hemagglutinin 177:189 hemagglutinin (HA) 177:194 BACKGROUND In the influenza A viruses, neuraminidase (NA), hemagglutinin (HA), PB2, NS1 and M are responsible for the disease pathogenicity. 25147684 1 8 theme A 146:146 arg1 viruses 148:154 the influenza A viruses 132:154 the influenza A viruses 132:154 BACKGROUND In the influenza A viruses, neuraminidase (NA), hemagglutinin (HA), PB2, NS1 and M are responsible for the disease pathogenicity. 25147684 1 8 theme A 146:146 arg1 NS1 202:204 NS1 202:204 NS1 202:204 BACKGROUND In the influenza A viruses, neuraminidase (NA), hemagglutinin (HA), PB2, NS1 and M are responsible for the disease pathogenicity. 25147684 1 8 theme A 146:146 arg1 neuraminidase 157:169 neuraminidase 157:169 neuraminidase (NA) 157:174 BACKGROUND In the influenza A viruses, neuraminidase (NA), hemagglutinin (HA), PB2, NS1 and M are responsible for the disease pathogenicity. 25147684 1 8 theme A 146:146 arg1 M 210:210 M 210:210 M 210:210 BACKGROUND In the influenza A viruses, neuraminidase (NA), hemagglutinin (HA), PB2, NS1 and M are responsible for the disease pathogenicity. 25147684 6 9 theme Ser-228 943:949 arg1 Ile-226 925:931 Ile-226 925:931 Ile-226 925:931 RESULTS In the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 were found. 25147684 6 9 theme Ser-228 943:949 arg1 Asp-190 956:962 Asp-190 956:962 Asp-190 956:962 RESULTS In the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 were found. 25147684 6 9 theme Ser-228 943:949 arg1 Pro-227 934:940 Pro-227 934:940 Pro-227 934:940 RESULTS In the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 were found. 25147684 6 9 theme Ser-228 943:949 arg1 site 913:916 the receptor binding site 892:916 the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 892:962 RESULTS In the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 were found. 25147684 6 9 theme Ser-228 943:949 arg1 HA 921:922 HA 921:922 HA 921:922 RESULTS In the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 were found. 25147684 6 9 theme Ser-228 943:949 arg1 Ser-228 943:949 Ser-228 943:949 Ser-228 943:949 RESULTS In the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 were found. 25147684 3 10 theme influenza 595:603 arg1 viruses 605:611 influenza viruses 595:611 influenza viruses 595:611 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 0 11 from Neuraminidase 47:59 arg1 Iran 112:115 Iran 112:115 Iran 112:115 Characterization of Variations in PB2, NS1, M, Neuraminidase and Hemagglutinin of Influenza A (H3N2) Viruses in Iran. 25147684 0 11 from Neuraminidase 47:59 arg1 Characterization 0:15 Characterization 0:15 Characterization of Variations in PB2, NS1, M, Neuraminidase and Hemagglutinin of Influenza A (H3N2) Viruses in Iran. 0:116 Characterization of Variations in PB2, NS1, M, Neuraminidase and Hemagglutinin of Influenza A (H3N2) Viruses in Iran. 25147684 0 12 from M 44:44 arg1 Iran 112:115 Iran 112:115 Iran 112:115 Characterization of Variations in PB2, NS1, M, Neuraminidase and Hemagglutinin of Influenza A (H3N2) Viruses in Iran. 25147684 0 12 from M 44:44 arg1 Characterization 0:15 Characterization 0:15 Characterization of Variations in PB2, NS1, M, Neuraminidase and Hemagglutinin of Influenza A (H3N2) Viruses in Iran. 0:116 Characterization of Variations in PB2, NS1, M, Neuraminidase and Hemagglutinin of Influenza A (H3N2) Viruses in Iran. 25147684 4 13 from alterations 664:674 arg1 genes 679:683 genes 679:683 genes 679:683 OBJECTIVES The goal of this study was to find the alterations in genes, which might be responsible in the virus pathogenesis. 25147684 5 14 theme Reverse 762:768 arg1 RT-PCR 811:816 RT-PCR 811:816 RT-PCR 811:816 MATERIALS AND METHODS Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing of HA, NA, PB2, NS and M genes were performed. 25147684 5 14 theme Reverse 762:768 arg1 reaction 801:808 Reverse transcription-polymerase chain reaction 762:808 Reverse transcription-polymerase chain reaction (RT-PCR) 762:817 MATERIALS AND METHODS Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing of HA, NA, PB2, NS and M genes were performed. 25147684 5 14 theme Reverse 762:768 arg1 METHODS 754:760 METHODS Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing 754:832 METHODS Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing 754:832 MATERIALS AND METHODS Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing of HA, NA, PB2, NS and M genes were performed. 25147684 3 15 theme PB2 505:507 arg1 genes 520:524 PB2, NS1 and M genes 505:524 genes 520:524 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 5 16 theme chain 795:799 arg1 RT-PCR 811:816 RT-PCR 811:816 RT-PCR 811:816 MATERIALS AND METHODS Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing of HA, NA, PB2, NS and M genes were performed. 25147684 5 16 theme chain 795:799 arg1 reaction 801:808 Reverse transcription-polymerase chain reaction 762:808 Reverse transcription-polymerase chain reaction (RT-PCR) 762:817 MATERIALS AND METHODS Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing of HA, NA, PB2, NS and M genes were performed. 25147684 5 16 theme chain 795:799 arg1 METHODS 754:760 METHODS Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing 754:832 METHODS Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing 754:832 MATERIALS AND METHODS Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing of HA, NA, PB2, NS and M genes were performed. 25147684 0 17 from Hemagglutinin 65:77 arg1 Iran 112:115 Iran 112:115 Iran 112:115 Characterization of Variations in PB2, NS1, M, Neuraminidase and Hemagglutinin of Influenza A (H3N2) Viruses in Iran. 25147684 0 17 from Hemagglutinin 65:77 arg1 Characterization 0:15 Characterization 0:15 Characterization of Variations in PB2, NS1, M, Neuraminidase and Hemagglutinin of Influenza A (H3N2) Viruses in Iran. 0:116 Characterization of Variations in PB2, NS1, M, Neuraminidase and Hemagglutinin of Influenza A (H3N2) Viruses in Iran. 25147684 0 18 from Variations 20:29 arg1 Neuraminidase 47:59 Neuraminidase 47:59 Neuraminidase 47:59 Characterization of Variations in PB2, NS1, M, Neuraminidase and Hemagglutinin of Influenza A (H3N2) Viruses in Iran. 25147684 0 18 from Variations 20:29 arg1 M 44:44 M 44:44 M 44:44 Characterization of Variations in PB2, NS1, M, Neuraminidase and Hemagglutinin of Influenza A (H3N2) Viruses in Iran. 25147684 0 18 from Variations 20:29 arg1 NS1 39:41 NS1 39:41 NS1 39:41 Characterization of Variations in PB2, NS1, M, Neuraminidase and Hemagglutinin of Influenza A (H3N2) Viruses in Iran. 25147684 0 18 from Variations 20:29 arg1 Hemagglutinin 65:77 Hemagglutinin 65:77 Hemagglutinin 65:77 Characterization of Variations in PB2, NS1, M, Neuraminidase and Hemagglutinin of Influenza A (H3N2) Viruses in Iran. 25147684 0 18 from Variations 20:29 arg1 PB2 34:36 PB2 34:36 PB2 34:36 Characterization of Variations in PB2, NS1, M, Neuraminidase and Hemagglutinin of Influenza A (H3N2) Viruses in Iran. 25147684 0 19 from Characterization 0:15 arg1 Neuraminidase 47:59 Neuraminidase 47:59 Neuraminidase 47:59 Characterization of Variations in PB2, NS1, M, Neuraminidase and Hemagglutinin of Influenza A (H3N2) Viruses in Iran. 25147684 0 19 from Characterization 0:15 arg1 M 44:44 M 44:44 M 44:44 Characterization of Variations in PB2, NS1, M, Neuraminidase and Hemagglutinin of Influenza A (H3N2) Viruses in Iran. 25147684 0 19 from Characterization 0:15 arg1 NS1 39:41 NS1 39:41 NS1 39:41 Characterization of Variations in PB2, NS1, M, Neuraminidase and Hemagglutinin of Influenza A (H3N2) Viruses in Iran. 25147684 0 19 from Characterization 0:15 arg1 Hemagglutinin 65:77 Hemagglutinin 65:77 Hemagglutinin 65:77 Characterization of Variations in PB2, NS1, M, Neuraminidase and Hemagglutinin of Influenza A (H3N2) Viruses in Iran. 25147684 0 19 from Characterization 0:15 arg1 PB2 34:36 PB2 34:36 PB2 34:36 Characterization of Variations in PB2, NS1, M, Neuraminidase and Hemagglutinin of Influenza A (H3N2) Viruses in Iran. 25147684 0 20 from NS1 39:41 arg1 Iran 112:115 Iran 112:115 Iran 112:115 Characterization of Variations in PB2, NS1, M, Neuraminidase and Hemagglutinin of Influenza A (H3N2) Viruses in Iran. 25147684 0 20 from NS1 39:41 arg1 Characterization 0:15 Characterization 0:15 Characterization of Variations in PB2, NS1, M, Neuraminidase and Hemagglutinin of Influenza A (H3N2) Viruses in Iran. 0:116 Characterization of Variations in PB2, NS1, M, Neuraminidase and Hemagglutinin of Influenza A (H3N2) Viruses in Iran. 25147684 5 21 dep METHODS 754:760 arg1 RT-PCR 811:816 RT-PCR 811:816 RT-PCR 811:816 MATERIALS AND METHODS Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing of HA, NA, PB2, NS and M genes were performed. 25147684 5 21 dep METHODS 754:760 arg1 sequencing 823:832 sequencing 823:832 sequencing 823:832 MATERIALS AND METHODS Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing of HA, NA, PB2, NS and M genes were performed. 25147684 5 21 dep METHODS 754:760 arg1 reaction 801:808 Reverse transcription-polymerase chain reaction 762:808 Reverse transcription-polymerase chain reaction (RT-PCR) 762:817 MATERIALS AND METHODS Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing of HA, NA, PB2, NS and M genes were performed. 25147684 5 21 dep METHODS 754:760 arg1 METHODS 754:760 METHODS Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing 754:832 METHODS Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing 754:832 MATERIALS AND METHODS Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing of HA, NA, PB2, NS and M genes were performed. 25147684 3 22 from substitutions 488:500 arg1 sites 414:418 the cleavage and receptor-binding sites 380:418 sites 414:418 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 3 22 from substitutions 488:500 arg1 genes 520:524 PB2, NS1 and M genes 505:524 genes 520:524 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 10 23 theme active 1350:1355 arg1 site 1357:1360 the enzyme active site 1339:1360 the enzyme active site 1339:1360 At residue 146 of NA, there was N-linked glycosylation, and Ile-222 was found in the enzyme active site. 25147684 0 24 theme Influenza 82:90 arg1 H3N2 95:98 H3N2 95:98 H3N2 95:98 Characterization of Variations in PB2, NS1, M, Neuraminidase and Hemagglutinin of Influenza A (H3N2) Viruses in Iran. 25147684 0 24 theme Influenza 82:90 arg1 A 92:92 Influenza A 82:92 Influenza A (H3N2) Viruses 82:107 Characterization of Variations in PB2, NS1, M, Neuraminidase and Hemagglutinin of Influenza A (H3N2) Viruses in Iran. 25147684 5 25 theme HA 837:838 arg1 MATERIALS 740:748 MATERIALS 740:748 MATERIALS 740:748 MATERIALS AND METHODS Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing of HA, NA, PB2, NS and M genes were performed. 25147684 5 25 theme HA 837:838 arg1 sequencing 823:832 sequencing 823:832 sequencing 823:832 MATERIALS AND METHODS Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing of HA, NA, PB2, NS and M genes were performed. 25147684 5 25 theme HA 837:838 arg1 reaction 801:808 Reverse transcription-polymerase chain reaction 762:808 Reverse transcription-polymerase chain reaction (RT-PCR) 762:817 MATERIALS AND METHODS Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing of HA, NA, PB2, NS and M genes were performed. 25147684 5 25 theme HA 837:838 arg1 METHODS 754:760 METHODS Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing 754:832 METHODS Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing 754:832 MATERIALS AND METHODS Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing of HA, NA, PB2, NS and M genes were performed. 25147684 0 26 from PB2 34:36 arg1 Iran 112:115 Iran 112:115 Iran 112:115 Characterization of Variations in PB2, NS1, M, Neuraminidase and Hemagglutinin of Influenza A (H3N2) Viruses in Iran. 25147684 0 26 from PB2 34:36 arg1 Characterization 0:15 Characterization 0:15 Characterization of Variations in PB2, NS1, M, Neuraminidase and Hemagglutinin of Influenza A (H3N2) Viruses in Iran. 0:116 Characterization of Variations in PB2, NS1, M, Neuraminidase and Hemagglutinin of Influenza A (H3N2) Viruses in Iran. 25147684 3 27 theme proteases 335:343 arg1 substitutions 488:500 substitutions 488:500 substitutions in PB2, NS1 and M genes 488:524 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 3 27 theme proteases 335:343 arg1 Binding 319:325 Binding 319:325 Binding of host proteases by the viral NA 319:359 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 3 27 theme proteases 335:343 arg1 number 421:426 number 421:426 number of oligosaccharide side chains of HA 421:463 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 3 27 theme proteases 335:343 arg1 shortening 466:475 shortening 466:475 shortening of NA 466:481 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 3 27 theme proteases 335:343 arg1 sequence 362:369 sequence 362:369 sequence of HA in the cleavage and receptor-binding sites 362:418 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 3 27 theme proteases 335:343 arg1 correlates 564:573 molecular correlates 554:573 molecular correlates of pathogenicity of influenza viruses 554:611 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 0 28 theme Variations 20:29 arg1 Characterization 0:15 Characterization 0:15 Characterization of Variations in PB2, NS1, M, Neuraminidase and Hemagglutinin of Influenza A (H3N2) Viruses in Iran. 0:116 Characterization of Variations in PB2, NS1, M, Neuraminidase and Hemagglutinin of Influenza A (H3N2) Viruses in Iran. 25147684 3 29 theme M 518:518 arg1 genes 520:524 PB2, NS1 and M genes 505:524 genes 520:524 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 8 30 theme viruses 1148:1154 arg1 PB2 1137:1139 PB2 1137:1139 PB2 of all viruses in this study 1137:1168 In NS1, Asp-92 and Ala-149 were detected and Lys-627 was found in PB2 of all viruses in this study. 25147684 11 31 contain had 1541:1543 arg2 pathogenicity 1549:1561 low pathogenicity 1545:1561 low pathogenicity 1545:1561 CONCLUSIONS The changes found in these five genes, compared to other studies, suggest that viruses studied in this research had the ability to bind to Neu Acα2,6 Gal linkage and had low pathogenicity. 25147684 11 31 contain had 1541:1543 arg1 viruses 1454:1460 viruses 1454:1460 viruses studied in this research 1454:1485 CONCLUSIONS The changes found in these five genes, compared to other studies, suggest that viruses studied in this research had the ability to bind to Neu Acα2,6 Gal linkage and had low pathogenicity. 25147684 5 32 theme NS 850:851 arg1 MATERIALS 740:748 MATERIALS 740:748 MATERIALS 740:748 MATERIALS AND METHODS Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing of HA, NA, PB2, NS and M genes were performed. 25147684 5 32 theme NS 850:851 arg1 sequencing 823:832 sequencing 823:832 sequencing 823:832 MATERIALS AND METHODS Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing of HA, NA, PB2, NS and M genes were performed. 25147684 5 32 theme NS 850:851 arg1 reaction 801:808 Reverse transcription-polymerase chain reaction 762:808 Reverse transcription-polymerase chain reaction (RT-PCR) 762:817 MATERIALS AND METHODS Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing of HA, NA, PB2, NS and M genes were performed. 25147684 5 32 theme NS 850:851 arg1 METHODS 754:760 METHODS Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing 754:832 METHODS Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing 754:832 MATERIALS AND METHODS Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing of HA, NA, PB2, NS and M genes were performed. 25147684 3 33 theme NS1 510:512 arg1 genes 520:524 PB2, NS1 and M genes 505:524 genes 520:524 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 11 34 theme Acα2,6 1518:1523 arg1 linkage 1529:1535 Neu Acα2,6 Gal linkage 1514:1535 Neu Acα2,6 Gal linkage 1514:1535 CONCLUSIONS The changes found in these five genes, compared to other studies, suggest that viruses studied in this research had the ability to bind to Neu Acα2,6 Gal linkage and had low pathogenicity. 25147684 11 35 dep CONCLUSIONS 1363:1373 arg1 changes 1379:1385 The changes 1375:1385 CONCLUSIONS The changes found in these five genes 1363:1411 CONCLUSIONS The changes found in these five genes, compared to other studies, suggest that viruses studied in this research had the ability to bind to Neu Acα2,6 Gal linkage and had low pathogenicity. 25147684 5 36 theme M 857:857 arg1 MATERIALS 740:748 MATERIALS 740:748 MATERIALS 740:748 MATERIALS AND METHODS Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing of HA, NA, PB2, NS and M genes were performed. 25147684 5 36 theme M 857:857 arg1 sequencing 823:832 sequencing 823:832 sequencing 823:832 MATERIALS AND METHODS Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing of HA, NA, PB2, NS and M genes were performed. 25147684 5 36 theme M 857:857 arg1 reaction 801:808 Reverse transcription-polymerase chain reaction 762:808 Reverse transcription-polymerase chain reaction (RT-PCR) 762:817 MATERIALS AND METHODS Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing of HA, NA, PB2, NS and M genes were performed. 25147684 5 36 theme M 857:857 arg1 METHODS 754:760 METHODS Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing 754:832 METHODS Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing 754:832 MATERIALS AND METHODS Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing of HA, NA, PB2, NS and M genes were performed. 25147684 3 37 theme HA 374:375 arg1 substitutions 488:500 substitutions 488:500 substitutions in PB2, NS1 and M genes 488:524 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 3 37 theme HA 374:375 arg1 Binding 319:325 Binding 319:325 Binding of host proteases by the viral NA 319:359 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 3 37 theme HA 374:375 arg1 number 421:426 number 421:426 number of oligosaccharide side chains of HA 421:463 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 3 37 theme HA 374:375 arg1 shortening 466:475 shortening 466:475 shortening of NA 466:481 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 3 37 theme HA 374:375 arg1 sequence 362:369 sequence 362:369 sequence of HA in the cleavage and receptor-binding sites 362:418 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 3 37 theme HA 374:375 arg1 correlates 564:573 molecular correlates 554:573 molecular correlates of pathogenicity of influenza viruses 554:611 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 7 38 gly glycosylation 1039:1051 arg2 sites 1053:1057 11-12 N-linked glycosylation sites 1024:1057 11-12 N-linked glycosylation sites 1024:1057 Arg was in the cleavage site of all viruses and 11-12 N-linked glycosylation sites were found. 25147684 7 38 gly glycosylation 1039:1051 arg2 11-12 1024:1028 11-12 1024:1028 11-12 1024:1028 Arg was in the cleavage site of all viruses and 11-12 N-linked glycosylation sites were found. 25147684 5 39 theme NA 841:842 arg1 MATERIALS 740:748 MATERIALS 740:748 MATERIALS 740:748 MATERIALS AND METHODS Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing of HA, NA, PB2, NS and M genes were performed. 25147684 5 39 theme NA 841:842 arg1 sequencing 823:832 sequencing 823:832 sequencing 823:832 MATERIALS AND METHODS Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing of HA, NA, PB2, NS and M genes were performed. 25147684 5 39 theme NA 841:842 arg1 reaction 801:808 Reverse transcription-polymerase chain reaction 762:808 Reverse transcription-polymerase chain reaction (RT-PCR) 762:817 MATERIALS AND METHODS Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing of HA, NA, PB2, NS and M genes were performed. 25147684 5 39 theme NA 841:842 arg1 METHODS 754:760 METHODS Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing 754:832 METHODS Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing 754:832 MATERIALS AND METHODS Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing of HA, NA, PB2, NS and M genes were performed. 25147684 2 40 theme pathogenicity 276:288 arg1 mechanism 263:271 The mechanism 259:271 The mechanism of pathogenicity 259:288 The mechanism of pathogenicity differs among these viruses. 25147684 5 41 theme PB2 845:847 arg1 MATERIALS 740:748 MATERIALS 740:748 MATERIALS 740:748 MATERIALS AND METHODS Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing of HA, NA, PB2, NS and M genes were performed. 25147684 5 41 theme PB2 845:847 arg1 sequencing 823:832 sequencing 823:832 sequencing 823:832 MATERIALS AND METHODS Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing of HA, NA, PB2, NS and M genes were performed. 25147684 5 41 theme PB2 845:847 arg1 reaction 801:808 Reverse transcription-polymerase chain reaction 762:808 Reverse transcription-polymerase chain reaction (RT-PCR) 762:817 MATERIALS AND METHODS Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing of HA, NA, PB2, NS and M genes were performed. 25147684 5 41 theme PB2 845:847 arg1 METHODS 754:760 METHODS Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing 754:832 METHODS Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing 754:832 MATERIALS AND METHODS Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing of HA, NA, PB2, NS and M genes were performed. 25147684 11 42 contain had 1487:1489 arg2 ability 1495:1501 the ability to bind to Neu Acα2,6 Gal linkage 1491:1535 the ability to bind to Neu Acα2,6 Gal linkage 1491:1535 CONCLUSIONS The changes found in these five genes, compared to other studies, suggest that viruses studied in this research had the ability to bind to Neu Acα2,6 Gal linkage and had low pathogenicity. 25147684 11 42 contain had 1487:1489 arg1 viruses 1454:1460 viruses 1454:1460 viruses studied in this research 1454:1485 CONCLUSIONS The changes found in these five genes, compared to other studies, suggest that viruses studied in this research had the ability to bind to Neu Acα2,6 Gal linkage and had low pathogenicity. 25147684 7 43 theme N-linked 1030:1037 arg1 sites 1053:1057 11-12 N-linked glycosylation sites 1024:1057 11-12 N-linked glycosylation sites 1024:1057 Arg was in the cleavage site of all viruses and 11-12 N-linked glycosylation sites were found. 25147684 3 44 theme molecular 554:562 arg1 substitutions 488:500 substitutions 488:500 substitutions in PB2, NS1 and M genes 488:524 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 3 44 theme molecular 554:562 arg1 Binding 319:325 Binding 319:325 Binding of host proteases by the viral NA 319:359 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 3 44 theme molecular 554:562 arg1 number 421:426 number 421:426 number of oligosaccharide side chains of HA 421:463 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 3 44 theme molecular 554:562 arg1 shortening 466:475 shortening 466:475 shortening of NA 466:481 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 3 44 theme molecular 554:562 arg1 sequence 362:369 sequence 362:369 sequence of HA in the cleavage and receptor-binding sites 362:418 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 3 44 theme molecular 554:562 arg1 correlates 564:573 molecular correlates 554:573 molecular correlates of pathogenicity of influenza viruses 554:611 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 8 45 from PB2 1137:1139 arg1 study 1164:1168 this study 1159:1168 this study 1159:1168 In NS1, Asp-92 and Ala-149 were detected and Lys-627 was found in PB2 of all viruses in this study. 25147684 3 46 from Binding 319:325 arg1 sites 414:418 the cleavage and receptor-binding sites 380:418 sites 414:418 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 3 46 from Binding 319:325 arg1 genes 520:524 PB2, NS1 and M genes 505:524 genes 520:524 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 6 47 theme binding 905:911 arg1 Ile-226 925:931 Ile-226 925:931 Ile-226 925:931 RESULTS In the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 were found. 25147684 6 47 theme binding 905:911 arg1 Asp-190 956:962 Asp-190 956:962 Asp-190 956:962 RESULTS In the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 were found. 25147684 6 47 theme binding 905:911 arg1 Pro-227 934:940 Pro-227 934:940 Pro-227 934:940 RESULTS In the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 were found. 25147684 6 47 theme binding 905:911 arg1 site 913:916 the receptor binding site 892:916 the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 892:962 RESULTS In the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 were found. 25147684 6 47 theme binding 905:911 arg1 HA 921:922 HA 921:922 HA 921:922 RESULTS In the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 were found. 25147684 6 47 theme binding 905:911 arg1 Ser-228 943:949 Ser-228 943:949 Ser-228 943:949 RESULTS In the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 were found. 25147684 6 48 from RESULTS 881:887 arg1 Ile-226 925:931 Ile-226 925:931 Ile-226 925:931 RESULTS In the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 were found. 25147684 6 48 from RESULTS 881:887 arg1 Asp-190 956:962 Asp-190 956:962 Asp-190 956:962 RESULTS In the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 were found. 25147684 6 48 from RESULTS 881:887 arg1 Pro-227 934:940 Pro-227 934:940 Pro-227 934:940 RESULTS In the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 were found. 25147684 6 48 from RESULTS 881:887 arg1 site 913:916 the receptor binding site 892:916 the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 892:962 RESULTS In the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 were found. 25147684 6 48 from RESULTS 881:887 arg1 HA 921:922 HA 921:922 HA 921:922 RESULTS In the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 were found. 25147684 6 48 from RESULTS 881:887 arg1 Ser-228 943:949 Ser-228 943:949 Ser-228 943:949 RESULTS In the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 were found. 25147684 3 49 theme oligosaccharide 431:445 arg1 chains 452:457 oligosaccharide side chains 431:457 oligosaccharide side chains of HA 431:463 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 10 50 theme NA 1276:1277 arg1 residue 1261:1267 residue 146 1261:1271 residue 146 of NA 1261:1277 At residue 146 of NA, there was N-linked glycosylation, and Ile-222 was found in the enzyme active site. 25147684 10 50 theme NA 1276:1277 arg1 NA 1276:1277 NA 1276:1277 NA 1276:1277 At residue 146 of NA, there was N-linked glycosylation, and Ile-222 was found in the enzyme active site. 25147684 6 51 theme Asp-190 956:962 arg1 Ile-226 925:931 Ile-226 925:931 Ile-226 925:931 RESULTS In the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 were found. 25147684 6 51 theme Asp-190 956:962 arg1 Asp-190 956:962 Asp-190 956:962 Asp-190 956:962 RESULTS In the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 were found. 25147684 6 51 theme Asp-190 956:962 arg1 Pro-227 934:940 Pro-227 934:940 Pro-227 934:940 RESULTS In the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 were found. 25147684 6 51 theme Asp-190 956:962 arg1 site 913:916 the receptor binding site 892:916 the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 892:962 RESULTS In the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 were found. 25147684 6 51 theme Asp-190 956:962 arg1 HA 921:922 HA 921:922 HA 921:922 RESULTS In the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 were found. 25147684 6 51 theme Asp-190 956:962 arg1 Ser-228 943:949 Ser-228 943:949 Ser-228 943:949 RESULTS In the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 were found. 25147684 3 52 theme HA 462:463 arg1 chains 452:457 oligosaccharide side chains 431:457 oligosaccharide side chains of HA 431:463 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 1 53 theme influenza 136:144 arg1 PB2 197:199 PB2 197:199 PB2 197:199 BACKGROUND In the influenza A viruses, neuraminidase (NA), hemagglutinin (HA), PB2, NS1 and M are responsible for the disease pathogenicity. 25147684 1 53 theme influenza 136:144 arg1 hemagglutinin 177:189 hemagglutinin 177:189 hemagglutinin (HA) 177:194 BACKGROUND In the influenza A viruses, neuraminidase (NA), hemagglutinin (HA), PB2, NS1 and M are responsible for the disease pathogenicity. 25147684 1 53 theme influenza 136:144 arg1 viruses 148:154 the influenza A viruses 132:154 the influenza A viruses 132:154 BACKGROUND In the influenza A viruses, neuraminidase (NA), hemagglutinin (HA), PB2, NS1 and M are responsible for the disease pathogenicity. 25147684 1 53 theme influenza 136:144 arg1 NS1 202:204 NS1 202:204 NS1 202:204 BACKGROUND In the influenza A viruses, neuraminidase (NA), hemagglutinin (HA), PB2, NS1 and M are responsible for the disease pathogenicity. 25147684 1 53 theme influenza 136:144 arg1 neuraminidase 157:169 neuraminidase 157:169 neuraminidase (NA) 157:174 BACKGROUND In the influenza A viruses, neuraminidase (NA), hemagglutinin (HA), PB2, NS1 and M are responsible for the disease pathogenicity. 25147684 1 53 theme influenza 136:144 arg1 M 210:210 M 210:210 M 210:210 BACKGROUND In the influenza A viruses, neuraminidase (NA), hemagglutinin (HA), PB2, NS1 and M are responsible for the disease pathogenicity. 25147684 10 54 theme N-linked 1290:1297 arg1 glycosylation 1299:1311 N-linked glycosylation 1290:1311 N-linked glycosylation 1290:1311 At residue 146 of NA, there was N-linked glycosylation, and Ile-222 was found in the enzyme active site. 25147684 3 55 theme chains 452:457 arg1 substitutions 488:500 substitutions 488:500 substitutions in PB2, NS1 and M genes 488:524 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 3 55 theme chains 452:457 arg1 Binding 319:325 Binding 319:325 Binding of host proteases by the viral NA 319:359 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 3 55 theme chains 452:457 arg1 number 421:426 number 421:426 number of oligosaccharide side chains of HA 421:463 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 3 55 theme chains 452:457 arg1 shortening 466:475 shortening 466:475 shortening of NA 466:481 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 3 55 theme chains 452:457 arg1 sequence 362:369 sequence 362:369 sequence of HA in the cleavage and receptor-binding sites 362:418 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 3 55 theme chains 452:457 arg1 correlates 564:573 molecular correlates 554:573 molecular correlates of pathogenicity of influenza viruses 554:611 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 9 56 theme M1 1202:1203 arg1 Val-28 1209:1214 Val-28 1209:1214 Val-28 1209:1214 Val-15, Thr-139 and Ala-218 of M1 and Val-28, Leu-54 and His-57 were found in M2 gene. 25147684 9 56 theme M1 1202:1203 arg1 Val-15 1171:1176 Val-15 1171:1176 Val-15 1171:1176 Val-15, Thr-139 and Ala-218 of M1 and Val-28, Leu-54 and His-57 were found in M2 gene. 25147684 9 56 theme M1 1202:1203 arg1 M1 1202:1203 M1 1202:1203 M1 1202:1203 Val-15, Thr-139 and Ala-218 of M1 and Val-28, Leu-54 and His-57 were found in M2 gene. 25147684 12 57 theme acid 1628:1631 arg1 level 1633:1637 the amino acid level 1618:1637 the amino acid level 1618:1637 It is important to mention that these changes were at the amino acid level and studies need to be performed on animals to investigate the significance of these findings. 25147684 3 58 theme viruses 605:611 arg1 pathogenicity 578:590 pathogenicity 578:590 pathogenicity of influenza viruses 578:611 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 0 59 theme Viruses 101:107 arg1 Neuraminidase 47:59 Neuraminidase 47:59 Neuraminidase 47:59 Characterization of Variations in PB2, NS1, M, Neuraminidase and Hemagglutinin of Influenza A (H3N2) Viruses in Iran. 25147684 0 59 theme Viruses 101:107 arg1 M 44:44 M 44:44 M 44:44 Characterization of Variations in PB2, NS1, M, Neuraminidase and Hemagglutinin of Influenza A (H3N2) Viruses in Iran. 25147684 0 59 theme Viruses 101:107 arg1 NS1 39:41 NS1 39:41 NS1 39:41 Characterization of Variations in PB2, NS1, M, Neuraminidase and Hemagglutinin of Influenza A (H3N2) Viruses in Iran. 25147684 0 59 theme Viruses 101:107 arg1 Hemagglutinin 65:77 Hemagglutinin 65:77 Hemagglutinin 65:77 Characterization of Variations in PB2, NS1, M, Neuraminidase and Hemagglutinin of Influenza A (H3N2) Viruses in Iran. 25147684 0 59 theme Viruses 101:107 arg1 PB2 34:36 PB2 34:36 PB2 34:36 Characterization of Variations in PB2, NS1, M, Neuraminidase and Hemagglutinin of Influenza A (H3N2) Viruses in Iran. 25147684 3 60 theme NA 480:481 arg1 substitutions 488:500 substitutions 488:500 substitutions in PB2, NS1 and M genes 488:524 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 3 60 theme NA 480:481 arg1 Binding 319:325 Binding 319:325 Binding of host proteases by the viral NA 319:359 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 3 60 theme NA 480:481 arg1 number 421:426 number 421:426 number of oligosaccharide side chains of HA 421:463 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 3 60 theme NA 480:481 arg1 shortening 466:475 shortening 466:475 shortening of NA 466:481 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 3 60 theme NA 480:481 arg1 sequence 362:369 sequence 362:369 sequence of HA in the cleavage and receptor-binding sites 362:418 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 3 60 theme NA 480:481 arg1 correlates 564:573 molecular correlates 554:573 molecular correlates of pathogenicity of influenza viruses 554:611 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 9 61 theme Val-28 1209:1214 arg1 Val-28 1209:1214 Val-28 1209:1214 Val-28 1209:1214 Val-15, Thr-139 and Ala-218 of M1 and Val-28, Leu-54 and His-57 were found in M2 gene. 25147684 9 61 theme Val-28 1209:1214 arg1 Val-15 1171:1176 Val-15 1171:1176 Val-15 1171:1176 Val-15, Thr-139 and Ala-218 of M1 and Val-28, Leu-54 and His-57 were found in M2 gene. 25147684 9 61 theme Val-28 1209:1214 arg1 M1 1202:1203 M1 1202:1203 M1 1202:1203 Val-15, Thr-139 and Ala-218 of M1 and Val-28, Leu-54 and His-57 were found in M2 gene. 25147684 7 62 link N-linked 1030:1037 arg1 sites 1053:1057 11-12 N-linked glycosylation sites 1024:1057 11-12 N-linked glycosylation sites 1024:1057 Arg was in the cleavage site of all viruses and 11-12 N-linked glycosylation sites were found. 25147684 4 63 dep OBJECTIVES 614:623 arg1 was 648:650 was 648:650 was 648:650 OBJECTIVES The goal of this study was to find the alterations in genes, which might be responsible in the virus pathogenesis. 25147684 9 64 located found 1240:1244 arg2 Leu-54 1217:1222 Leu-54 1217:1222 Leu-54 1217:1222 Val-15, Thr-139 and Ala-218 of M1 and Val-28, Leu-54 and His-57 were found in M2 gene. 25147684 9 64 located found 1240:1244 arg2 Val-15 1171:1176 Val-15 1171:1176 Val-15 1171:1176 Val-15, Thr-139 and Ala-218 of M1 and Val-28, Leu-54 and His-57 were found in M2 gene. 25147684 9 64 located found 1240:1244 arg2 M1 1202:1203 M1 1202:1203 M1 1202:1203 Val-15, Thr-139 and Ala-218 of M1 and Val-28, Leu-54 and His-57 were found in M2 gene. 25147684 9 64 located found 1240:1244 arg2 His-57 1228:1233 His-57 1228:1233 His-57 1228:1233 Val-15, Thr-139 and Ala-218 of M1 and Val-28, Leu-54 and His-57 were found in M2 gene. 25147684 9 64 located found 1240:1244 arg1 gene 1252:1255 M2 gene 1249:1255 M2 gene 1249:1255 Val-15, Thr-139 and Ala-218 of M1 and Val-28, Leu-54 and His-57 were found in M2 gene. 25147684 9 64 located found 1240:1244 arg2 Val-28 1209:1214 Val-28 1209:1214 Val-28 1209:1214 Val-15, Thr-139 and Ala-218 of M1 and Val-28, Leu-54 and His-57 were found in M2 gene. 25147684 9 64 located found 1240:1244 arg2 Thr-139 1179:1185 Thr-139 1179:1185 Thr-139 1179:1185 Val-15, Thr-139 and Ala-218 of M1 and Val-28, Leu-54 and His-57 were found in M2 gene. 25147684 9 64 located found 1240:1244 arg2 Ala-218 1191:1197 Ala-218 1191:1197 Ala-218 1191:1197 Val-15, Thr-139 and Ala-218 of M1 and Val-28, Leu-54 and His-57 were found in M2 gene. 25147684 5 65 dep HA 837:838 arg1 genes 859:863 genes 859:863 genes 859:863 MATERIALS AND METHODS Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing of HA, NA, PB2, NS and M genes were performed. 25147684 5 66 theme transcription-polymerase 770:793 arg1 RT-PCR 811:816 RT-PCR 811:816 RT-PCR 811:816 MATERIALS AND METHODS Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing of HA, NA, PB2, NS and M genes were performed. 25147684 5 66 theme transcription-polymerase 770:793 arg1 reaction 801:808 Reverse transcription-polymerase chain reaction 762:808 Reverse transcription-polymerase chain reaction (RT-PCR) 762:817 MATERIALS AND METHODS Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing of HA, NA, PB2, NS and M genes were performed. 25147684 5 66 theme transcription-polymerase 770:793 arg1 METHODS 754:760 METHODS Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing 754:832 METHODS Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing 754:832 MATERIALS AND METHODS Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing of HA, NA, PB2, NS and M genes were performed. 25147684 12 67 theme findings 1724:1731 arg1 significance 1702:1713 the significance 1698:1713 the significance of these findings 1698:1731 It is important to mention that these changes were at the amino acid level and studies need to be performed on animals to investigate the significance of these findings. 25147684 6 68 theme Ile-226 925:931 arg1 Ile-226 925:931 Ile-226 925:931 Ile-226 925:931 RESULTS In the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 were found. 25147684 6 68 theme Ile-226 925:931 arg1 Asp-190 956:962 Asp-190 956:962 Asp-190 956:962 RESULTS In the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 were found. 25147684 6 68 theme Ile-226 925:931 arg1 Pro-227 934:940 Pro-227 934:940 Pro-227 934:940 RESULTS In the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 were found. 25147684 6 68 theme Ile-226 925:931 arg1 site 913:916 the receptor binding site 892:916 the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 892:962 RESULTS In the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 were found. 25147684 6 68 theme Ile-226 925:931 arg1 HA 921:922 HA 921:922 HA 921:922 RESULTS In the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 were found. 25147684 6 68 theme Ile-226 925:931 arg1 Ser-228 943:949 Ser-228 943:949 Ser-228 943:949 RESULTS In the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 were found. 25147684 4 69 from pathogenesis 726:737 arg1 responsible 701:711 responsible 701:711 responsible 701:711 OBJECTIVES The goal of this study was to find the alterations in genes, which might be responsible in the virus pathogenesis. 25147684 3 70 from number 421:426 arg1 sites 414:418 the cleavage and receptor-binding sites 380:418 sites 414:418 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 3 70 from number 421:426 arg1 genes 520:524 PB2, NS1 and M genes 505:524 genes 520:524 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 11 71 theme other 1426:1430 arg1 studies 1432:1438 other studies 1426:1438 other studies 1426:1438 CONCLUSIONS The changes found in these five genes, compared to other studies, suggest that viruses studied in this research had the ability to bind to Neu Acα2,6 Gal linkage and had low pathogenicity. 25147684 7 72 theme cleavage 991:998 arg1 site 1000:1003 the cleavage site 987:1003 the cleavage site of all viruses 987:1018 Arg was in the cleavage site of all viruses and 11-12 N-linked glycosylation sites were found. 25147684 7 72 theme cleavage 991:998 arg1 viruses 1012:1018 all viruses 1008:1018 all viruses 1008:1018 Arg was in the cleavage site of all viruses and 11-12 N-linked glycosylation sites were found. 25147684 1 73 theme disease 236:242 arg1 pathogenicity 244:256 the disease pathogenicity 232:256 the disease pathogenicity 232:256 BACKGROUND In the influenza A viruses, neuraminidase (NA), hemagglutinin (HA), PB2, NS1 and M are responsible for the disease pathogenicity. 25147684 9 74 theme M2 1249:1250 arg1 gene 1252:1255 M2 gene 1249:1255 M2 gene 1249:1255 Val-15, Thr-139 and Ala-218 of M1 and Val-28, Leu-54 and His-57 were found in M2 gene. 25147684 4 75 from responsible 701:711 arg1 pathogenesis 726:737 the virus pathogenesis 716:737 the virus pathogenesis 716:737 OBJECTIVES The goal of this study was to find the alterations in genes, which might be responsible in the virus pathogenesis. 25147684 1 76 from BACKGROUND 118:127 arg1 PB2 197:199 PB2 197:199 PB2 197:199 BACKGROUND In the influenza A viruses, neuraminidase (NA), hemagglutinin (HA), PB2, NS1 and M are responsible for the disease pathogenicity. 25147684 1 76 from BACKGROUND 118:127 arg1 hemagglutinin 177:189 hemagglutinin 177:189 hemagglutinin (HA) 177:194 BACKGROUND In the influenza A viruses, neuraminidase (NA), hemagglutinin (HA), PB2, NS1 and M are responsible for the disease pathogenicity. 25147684 1 76 from BACKGROUND 118:127 arg1 viruses 148:154 the influenza A viruses 132:154 the influenza A viruses 132:154 BACKGROUND In the influenza A viruses, neuraminidase (NA), hemagglutinin (HA), PB2, NS1 and M are responsible for the disease pathogenicity. 25147684 1 76 from BACKGROUND 118:127 arg1 NS1 202:204 NS1 202:204 NS1 202:204 BACKGROUND In the influenza A viruses, neuraminidase (NA), hemagglutinin (HA), PB2, NS1 and M are responsible for the disease pathogenicity. 25147684 1 76 from BACKGROUND 118:127 arg1 neuraminidase 157:169 neuraminidase 157:169 neuraminidase (NA) 157:174 BACKGROUND In the influenza A viruses, neuraminidase (NA), hemagglutinin (HA), PB2, NS1 and M are responsible for the disease pathogenicity. 25147684 1 76 from BACKGROUND 118:127 arg1 M 210:210 M 210:210 M 210:210 BACKGROUND In the influenza A viruses, neuraminidase (NA), hemagglutinin (HA), PB2, NS1 and M are responsible for the disease pathogenicity. 25147684 0 77 theme A 92:92 arg1 Viruses 101:107 Influenza A (H3N2) Viruses 82:107 Influenza A (H3N2) Viruses 82:107 Characterization of Variations in PB2, NS1, M, Neuraminidase and Hemagglutinin of Influenza A (H3N2) Viruses in Iran. 25147684 6 78 theme receptor 896:903 arg1 Ile-226 925:931 Ile-226 925:931 Ile-226 925:931 RESULTS In the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 were found. 25147684 6 78 theme receptor 896:903 arg1 Asp-190 956:962 Asp-190 956:962 Asp-190 956:962 RESULTS In the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 were found. 25147684 6 78 theme receptor 896:903 arg1 Pro-227 934:940 Pro-227 934:940 Pro-227 934:940 RESULTS In the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 were found. 25147684 6 78 theme receptor 896:903 arg1 site 913:916 the receptor binding site 892:916 the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 892:962 RESULTS In the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 were found. 25147684 6 78 theme receptor 896:903 arg1 HA 921:922 HA 921:922 HA 921:922 RESULTS In the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 were found. 25147684 6 78 theme receptor 896:903 arg1 Ser-228 943:949 Ser-228 943:949 Ser-228 943:949 RESULTS In the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 were found. 25147684 3 79 theme viral 352:356 arg1 NA 358:359 the viral NA 348:359 the viral NA 348:359 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 3 80 from shortening 466:475 arg1 sites 414:418 the cleavage and receptor-binding sites 380:418 sites 414:418 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 3 80 from shortening 466:475 arg1 genes 520:524 PB2, NS1 and M genes 505:524 genes 520:524 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 11 81 located found 1387:1391 arg1 genes 1407:1411 these five genes 1396:1411 these five genes 1396:1411 CONCLUSIONS The changes found in these five genes, compared to other studies, suggest that viruses studied in this research had the ability to bind to Neu Acα2,6 Gal linkage and had low pathogenicity. 25147684 11 81 located found 1387:1391 arg2 changes 1379:1385 The changes 1375:1385 CONCLUSIONS The changes found in these five genes 1363:1411 CONCLUSIONS The changes found in these five genes, compared to other studies, suggest that viruses studied in this research had the ability to bind to Neu Acα2,6 Gal linkage and had low pathogenicity. 25147684 3 82 theme host 330:333 arg1 proteases 335:343 host proteases 330:343 host proteases 330:343 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 10 83 located found 1330:1334 arg2 Ile-222 1318:1324 Ile-222 1318:1324 Ile-222 1318:1324 At residue 146 of NA, there was N-linked glycosylation, and Ile-222 was found in the enzyme active site. 25147684 10 83 located found 1330:1334 arg1 site 1357:1360 the enzyme active site 1339:1360 the enzyme active site 1339:1360 At residue 146 of NA, there was N-linked glycosylation, and Ile-222 was found in the enzyme active site. 25147684 6 84 theme Pro-227 934:940 arg1 Ile-226 925:931 Ile-226 925:931 Ile-226 925:931 RESULTS In the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 were found. 25147684 6 84 theme Pro-227 934:940 arg1 Asp-190 956:962 Asp-190 956:962 Asp-190 956:962 RESULTS In the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 were found. 25147684 6 84 theme Pro-227 934:940 arg1 Pro-227 934:940 Pro-227 934:940 Pro-227 934:940 RESULTS In the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 were found. 25147684 6 84 theme Pro-227 934:940 arg1 site 913:916 the receptor binding site 892:916 the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 892:962 RESULTS In the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 were found. 25147684 6 84 theme Pro-227 934:940 arg1 HA 921:922 HA 921:922 HA 921:922 RESULTS In the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 were found. 25147684 6 84 theme Pro-227 934:940 arg1 Ser-228 943:949 Ser-228 943:949 Ser-228 943:949 RESULTS In the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 were found. 25147684 3 85 from sequence 362:369 arg1 sites 414:418 the cleavage and receptor-binding sites 380:418 sites 414:418 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 3 85 from sequence 362:369 arg1 genes 520:524 PB2, NS1 and M genes 505:524 genes 520:524 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 3 86 theme cleavage 384:391 arg1 sites 414:418 the cleavage and receptor-binding sites 380:418 sites 414:418 Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. 25147684 11 87 theme Gal 1525:1527 arg1 linkage 1529:1535 Neu Acα2,6 Gal linkage 1514:1535 Neu Acα2,6 Gal linkage 1514:1535 CONCLUSIONS The changes found in these five genes, compared to other studies, suggest that viruses studied in this research had the ability to bind to Neu Acα2,6 Gal linkage and had low pathogenicity. 25147684 7 88 theme glycosylation 1039:1051 arg1 sites 1053:1057 11-12 N-linked glycosylation sites 1024:1057 11-12 N-linked glycosylation sites 1024:1057 Arg was in the cleavage site of all viruses and 11-12 N-linked glycosylation sites were found. 25147684 4 89 theme study 642:646 arg1 goal 629:632 The goal 625:632 The goal of this study 625:646 OBJECTIVES The goal of this study was to find the alterations in genes, which might be responsible in the virus pathogenesis. 25147684 11 90 theme Neu 1514:1516 arg1 linkage 1529:1535 Neu Acα2,6 Gal linkage 1514:1535 Neu Acα2,6 Gal linkage 1514:1535 CONCLUSIONS The changes found in these five genes, compared to other studies, suggest that viruses studied in this research had the ability to bind to Neu Acα2,6 Gal linkage and had low pathogenicity. 25147684 8 91 located detected 1103:1110 arg1 NS1 1074:1076 NS1 1074:1076 NS1 1074:1076 In NS1, Asp-92 and Ala-149 were detected and Lys-627 was found in PB2 of all viruses in this study. 25147684 8 91 located detected 1103:1110 arg2 Ala-149 1090:1096 Ala-149 1090:1096 Ala-149 1090:1096 In NS1, Asp-92 and Ala-149 were detected and Lys-627 was found in PB2 of all viruses in this study. 25147684 8 91 located detected 1103:1110 arg2 Asp-92 1079:1084 Asp-92 1079:1084 Asp-92 1079:1084 In NS1, Asp-92 and Ala-149 were detected and Lys-627 was found in PB2 of all viruses in this study. 25147684 6 92 theme HA 921:922 arg1 Ile-226 925:931 Ile-226 925:931 Ile-226 925:931 RESULTS In the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 were found. 25147684 6 92 theme HA 921:922 arg1 Asp-190 956:962 Asp-190 956:962 Asp-190 956:962 RESULTS In the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 were found. 25147684 6 92 theme HA 921:922 arg1 Pro-227 934:940 Pro-227 934:940 Pro-227 934:940 RESULTS In the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 were found. 25147684 6 92 theme HA 921:922 arg1 site 913:916 the receptor binding site 892:916 the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 892:962 RESULTS In the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 were found. 25147684 6 92 theme HA 921:922 arg1 HA 921:922 HA 921:922 HA 921:922 RESULTS In the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 were found. 25147684 6 92 theme HA 921:922 arg1 Ser-228 943:949 Ser-228 943:949 Ser-228 943:949 RESULTS In the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 were found. 25147684 10 93 theme enzyme 1343:1348 arg1 site 1357:1360 the enzyme active site 1339:1360 the enzyme active site 1339:1360 At residue 146 of NA, there was N-linked glycosylation, and Ile-222 was found in the enzyme active site. 25147684 11 94 theme low 1545:1547 arg1 pathogenicity 1549:1561 low pathogenicity 1545:1561 low pathogenicity 1545:1561 CONCLUSIONS The changes found in these five genes, compared to other studies, suggest that viruses studied in this research had the ability to bind to Neu Acα2,6 Gal linkage and had low pathogenicity. 28993419 7 0 theme regulatory 1460:1469 arg1 network 1471:1477 a novel regulatory network 1452:1477 a novel regulatory network that connects isoprenoid lipid biosynthesis and LLO substrate assembly 1452:1548 In addition, our proteomics approach revealed a novel regulatory network that connects isoprenoid lipid biosynthesis and LLO substrate assembly. 28993419 7 1 theme isoprenoid 1493:1502 arg1 biosynthesis 1510:1521 isoprenoid lipid biosynthesis 1493:1521 isoprenoid lipid biosynthesis 1493:1521 In addition, our proteomics approach revealed a novel regulatory network that connects isoprenoid lipid biosynthesis and LLO substrate assembly. 28993419 4 2 theme labeling 766:773 arg1 approach 783:790 coupling stable isotope labeling (SILAC) approach 742:790 coupling stable isotope labeling (SILAC) approach to parallel reaction monitoring (PRM) mass spectrometry (MS) 742:851 We developed a sensitive approach to examine glycosylation site occupancy in Saccharomyces cerevisiae by coupling stable isotope labeling (SILAC) approach to parallel reaction monitoring (PRM) mass spectrometry (MS). 28993419 5 3 theme glycosylation 956:968 arg1 sites 970:974 novel glycosylation sites 950:974 novel glycosylation sites dependent on the Ost3p and Ost6p regulatory subunits of OST 950:1034 We combined the method with genetic tools and validated the approach with the identification of novel glycosylation sites dependent on the Ost3p and Ost6p regulatory subunits of OST. 28993419 0 4 from Profiling 13:21 arg1 cerevisiae 82:91 Yeast Saccharomyces cerevisiae 62:91 Yeast Saccharomyces cerevisiae 62:91 Quantitative Profiling of N-linked Glycosylation Machinery in Yeast Saccharomyces cerevisiae. 28993419 0 5 link N-linked 26:33 arg1 Machinery 49:57 N-linked Glycosylation Machinery 26:57 N-linked Glycosylation Machinery 26:57 Quantitative Profiling of N-linked Glycosylation Machinery in Yeast Saccharomyces cerevisiae. 28993419 4 6 theme isotope 758:764 arg1 SILAC 776:780 SILAC 776:780 SILAC 776:780 We developed a sensitive approach to examine glycosylation site occupancy in Saccharomyces cerevisiae by coupling stable isotope labeling (SILAC) approach to parallel reaction monitoring (PRM) mass spectrometry (MS). 28993419 4 6 theme isotope 758:764 arg1 labeling 766:773 coupling stable isotope labeling 742:773 coupling stable isotope labeling (SILAC) approach to parallel reaction monitoring (PRM) mass spectrometry (MS) 742:851 We developed a sensitive approach to examine glycosylation site occupancy in Saccharomyces cerevisiae by coupling stable isotope labeling (SILAC) approach to parallel reaction monitoring (PRM) mass spectrometry (MS). 28993419 6 7 theme OST 1178:1180 arg1 output 1168:1173 the systemic output 1155:1173 the systemic output of OST 1155:1180 Based on the observations that alternations in LLO substrate structure and OST subunits activity differentially alter the systemic output of OST, we conclude that sequon recognition is a direct property of the catalytic subunit Stt3p, auxiliary subunits such as Ost3p and Ost6p extend the OST substrate range by modulating interfering pathways such as protein folding. 28993419 7 8 theme LLO 1527:1529 arg1 assembly 1541:1548 LLO substrate assembly 1527:1548 LLO substrate assembly 1527:1548 In addition, our proteomics approach revealed a novel regulatory network that connects isoprenoid lipid biosynthesis and LLO substrate assembly. 28993419 6 9 from alternations 1068:1079 arg1 activity 1125:1132 LLO substrate structure and OST subunits activity 1084:1132 LLO substrate structure and OST subunits activity 1084:1132 Based on the observations that alternations in LLO substrate structure and OST subunits activity differentially alter the systemic output of OST, we conclude that sequon recognition is a direct property of the catalytic subunit Stt3p, auxiliary subunits such as Ost3p and Ost6p extend the OST substrate range by modulating interfering pathways such as protein folding. 28993419 2 10 theme oligosaccharide 347:361 arg1 assembly 318:325 the assembly 314:325 the assembly of the lipid-linked oligosaccharide (LLO), which is then transferred to the asparagine residues on the polypeptides by the enzyme oligosaccharyltransferase (OST) 314:487 The N-linked glycosylation machinery involves enzymes responsible for the assembly of the lipid-linked oligosaccharide (LLO), which is then transferred to the asparagine residues on the polypeptides by the enzyme oligosaccharyltransferase (OST). 28993419 1 11 dep structure 192:200 arg1 the 188:190 the 188:190 the 188:190 Asparagine-linked glycosylation is a common posttranslational protein modification regulating the structure, stability and function of many proteins. 28993419 1 12 link Asparagine-linked 94:110 arg1 modification 164:175 a common posttranslational protein modification 129:175 a common posttranslational protein modification regulating the structure, stability and function of many proteins 129:241 Asparagine-linked glycosylation is a common posttranslational protein modification regulating the structure, stability and function of many proteins. 28993419 1 12 link Asparagine-linked 94:110 arg1 glycosylation 112:124 Asparagine-linked glycosylation 94:124 Asparagine-linked glycosylation 94:124 Asparagine-linked glycosylation is a common posttranslational protein modification regulating the structure, stability and function of many proteins. 28993419 7 13 theme lipid 1504:1508 arg1 biosynthesis 1510:1521 isoprenoid lipid biosynthesis 1493:1521 isoprenoid lipid biosynthesis 1493:1521 In addition, our proteomics approach revealed a novel regulatory network that connects isoprenoid lipid biosynthesis and LLO substrate assembly. 28993419 5 14 theme regulatory 1009:1018 arg1 subunits 1020:1027 regulatory subunits 1009:1027 regulatory subunits of OST 1009:1034 We combined the method with genetic tools and validated the approach with the identification of novel glycosylation sites dependent on the Ost3p and Ost6p regulatory subunits of OST. 28993419 2 15 theme lipid-linked 334:345 arg1 LLO 364:366 LLO 364:366 LLO 364:366 The N-linked glycosylation machinery involves enzymes responsible for the assembly of the lipid-linked oligosaccharide (LLO), which is then transferred to the asparagine residues on the polypeptides by the enzyme oligosaccharyltransferase (OST). 28993419 2 15 theme lipid-linked 334:345 arg1 oligosaccharide 347:361 the lipid-linked oligosaccharide 330:361 the lipid-linked oligosaccharide (LLO) 330:367 The N-linked glycosylation machinery involves enzymes responsible for the assembly of the lipid-linked oligosaccharide (LLO), which is then transferred to the asparagine residues on the polypeptides by the enzyme oligosaccharyltransferase (OST). 28993419 5 16 theme dependent 976:984 arg1 sites 970:974 novel glycosylation sites 950:974 novel glycosylation sites dependent on the Ost3p and Ost6p regulatory subunits of OST 950:1034 We combined the method with genetic tools and validated the approach with the identification of novel glycosylation sites dependent on the Ost3p and Ost6p regulatory subunits of OST. 28993419 5 17 theme genetic 882:888 arg1 tools 890:894 genetic tools 882:894 genetic tools 882:894 We combined the method with genetic tools and validated the approach with the identification of novel glycosylation sites dependent on the Ost3p and Ost6p regulatory subunits of OST. 28993419 3 18 theme protein 519:525 arg1 glycosylation 527:539 protein glycosylation 519:539 protein glycosylation 519:539 A major goal in the study of protein glycosylation is to establish quantitative methods for the analysis of site-specific extent of glycosylation. 28993419 4 19 theme parallel 795:802 arg1 MS 849:850 MS 849:850 MS 849:850 We developed a sensitive approach to examine glycosylation site occupancy in Saccharomyces cerevisiae by coupling stable isotope labeling (SILAC) approach to parallel reaction monitoring (PRM) mass spectrometry (MS). 28993419 4 19 theme parallel 795:802 arg1 spectrometry 835:846 parallel reaction monitoring (PRM) mass spectrometry 795:846 parallel reaction monitoring (PRM) mass spectrometry (MS) 795:851 We developed a sensitive approach to examine glycosylation site occupancy in Saccharomyces cerevisiae by coupling stable isotope labeling (SILAC) approach to parallel reaction monitoring (PRM) mass spectrometry (MS). 28993419 4 20 theme mass 830:833 arg1 MS 849:850 MS 849:850 MS 849:850 We developed a sensitive approach to examine glycosylation site occupancy in Saccharomyces cerevisiae by coupling stable isotope labeling (SILAC) approach to parallel reaction monitoring (PRM) mass spectrometry (MS). 28993419 4 20 theme mass 830:833 arg1 spectrometry 835:846 parallel reaction monitoring (PRM) mass spectrometry 795:846 parallel reaction monitoring (PRM) mass spectrometry (MS) 795:851 We developed a sensitive approach to examine glycosylation site occupancy in Saccharomyces cerevisiae by coupling stable isotope labeling (SILAC) approach to parallel reaction monitoring (PRM) mass spectrometry (MS). 28993419 6 21 theme substrate 1088:1096 arg1 structure 1098:1106 substrate structure 1088:1106 substrate structure 1088:1106 Based on the observations that alternations in LLO substrate structure and OST subunits activity differentially alter the systemic output of OST, we conclude that sequon recognition is a direct property of the catalytic subunit Stt3p, auxiliary subunits such as Ost3p and Ost6p extend the OST substrate range by modulating interfering pathways such as protein folding. 28993419 6 22 theme protein 1389:1395 arg1 folding 1397:1403 protein folding 1389:1403 protein folding 1389:1403 Based on the observations that alternations in LLO substrate structure and OST subunits activity differentially alter the systemic output of OST, we conclude that sequon recognition is a direct property of the catalytic subunit Stt3p, auxiliary subunits such as Ost3p and Ost6p extend the OST substrate range by modulating interfering pathways such as protein folding. 28993419 4 23 gly glycosylation 682:694 arg2 occupancy 701:709 glycosylation site occupancy 682:709 glycosylation site occupancy in Saccharomyces cerevisiae by coupling stable isotope labeling (SILAC) approach to parallel reaction monitoring (PRM) mass spectrometry (MS) 682:851 We developed a sensitive approach to examine glycosylation site occupancy in Saccharomyces cerevisiae by coupling stable isotope labeling (SILAC) approach to parallel reaction monitoring (PRM) mass spectrometry (MS). 28993419 4 23 gly glycosylation 682:694 arg2 site 696:699 glycosylation site occupancy 682:709 glycosylation site occupancy in Saccharomyces cerevisiae by coupling stable isotope labeling (SILAC) approach to parallel reaction monitoring (PRM) mass spectrometry (MS) 682:851 We developed a sensitive approach to examine glycosylation site occupancy in Saccharomyces cerevisiae by coupling stable isotope labeling (SILAC) approach to parallel reaction monitoring (PRM) mass spectrometry (MS). 28993419 1 24 theme Asparagine-linked 94:110 arg1 modification 164:175 a common posttranslational protein modification 129:175 a common posttranslational protein modification regulating the structure, stability and function of many proteins 129:241 Asparagine-linked glycosylation is a common posttranslational protein modification regulating the structure, stability and function of many proteins. 28993419 1 24 theme Asparagine-linked 94:110 arg1 glycosylation 112:124 Asparagine-linked glycosylation 94:124 Asparagine-linked glycosylation 94:124 Asparagine-linked glycosylation is a common posttranslational protein modification regulating the structure, stability and function of many proteins. 28993419 6 25 theme subunits 1116:1123 arg1 activity 1125:1132 LLO substrate structure and OST subunits activity 1084:1132 LLO substrate structure and OST subunits activity 1084:1132 Based on the observations that alternations in LLO substrate structure and OST subunits activity differentially alter the systemic output of OST, we conclude that sequon recognition is a direct property of the catalytic subunit Stt3p, auxiliary subunits such as Ost3p and Ost6p extend the OST substrate range by modulating interfering pathways such as protein folding. 28993419 6 26 theme sequon 1200:1205 arg1 property 1231:1238 a direct property 1222:1238 a direct property of the catalytic subunit Stt3p 1222:1269 Based on the observations that alternations in LLO substrate structure and OST subunits activity differentially alter the systemic output of OST, we conclude that sequon recognition is a direct property of the catalytic subunit Stt3p, auxiliary subunits such as Ost3p and Ost6p extend the OST substrate range by modulating interfering pathways such as protein folding. 28993419 6 26 theme sequon 1200:1205 arg1 recognition 1207:1217 sequon recognition 1200:1217 sequon recognition 1200:1217 Based on the observations that alternations in LLO substrate structure and OST subunits activity differentially alter the systemic output of OST, we conclude that sequon recognition is a direct property of the catalytic subunit Stt3p, auxiliary subunits such as Ost3p and Ost6p extend the OST substrate range by modulating interfering pathways such as protein folding. 28993419 6 27 theme structure 1098:1106 arg1 activity 1125:1132 LLO substrate structure and OST subunits activity 1084:1132 LLO substrate structure and OST subunits activity 1084:1132 Based on the observations that alternations in LLO substrate structure and OST subunits activity differentially alter the systemic output of OST, we conclude that sequon recognition is a direct property of the catalytic subunit Stt3p, auxiliary subunits such as Ost3p and Ost6p extend the OST substrate range by modulating interfering pathways such as protein folding. 28993419 3 28 theme extent 612:617 arg1 analysis 586:593 the analysis 582:593 the analysis of site-specific extent of glycosylation 582:634 A major goal in the study of protein glycosylation is to establish quantitative methods for the analysis of site-specific extent of glycosylation. 28993419 6 29 theme OST 1112:1114 arg1 subunits 1116:1123 OST subunits 1112:1123 OST subunits 1112:1123 Based on the observations that alternations in LLO substrate structure and OST subunits activity differentially alter the systemic output of OST, we conclude that sequon recognition is a direct property of the catalytic subunit Stt3p, auxiliary subunits such as Ost3p and Ost6p extend the OST substrate range by modulating interfering pathways such as protein folding. 28993419 0 30 theme Quantitative 0:11 arg1 Profiling 13:21 Quantitative Profiling 0:21 Quantitative Profiling of N-linked Glycosylation Machinery in Yeast Saccharomyces cerevisiae 0:91 Quantitative Profiling of N-linked Glycosylation Machinery in Yeast Saccharomyces cerevisiae. 28993419 3 31 theme site-specific 598:610 arg1 extent 612:617 site-specific extent 598:617 site-specific extent of glycosylation 598:634 A major goal in the study of protein glycosylation is to establish quantitative methods for the analysis of site-specific extent of glycosylation. 28993419 2 32 from residues 414:421 arg1 polypeptides 430:441 the polypeptides 426:441 the polypeptides 426:441 The N-linked glycosylation machinery involves enzymes responsible for the assembly of the lipid-linked oligosaccharide (LLO), which is then transferred to the asparagine residues on the polypeptides by the enzyme oligosaccharyltransferase (OST). 28993419 4 33 from occupancy 701:709 arg1 cerevisiae 728:737 Saccharomyces cerevisiae 714:737 Saccharomyces cerevisiae 714:737 We developed a sensitive approach to examine glycosylation site occupancy in Saccharomyces cerevisiae by coupling stable isotope labeling (SILAC) approach to parallel reaction monitoring (PRM) mass spectrometry (MS). 28993419 1 34 theme many 229:232 arg1 proteins 234:241 many proteins 229:241 many proteins 229:241 Asparagine-linked glycosylation is a common posttranslational protein modification regulating the structure, stability and function of many proteins. 28993419 0 35 theme N-linked 26:33 arg1 Machinery 49:57 N-linked Glycosylation Machinery 26:57 N-linked Glycosylation Machinery 26:57 Quantitative Profiling of N-linked Glycosylation Machinery in Yeast Saccharomyces cerevisiae. 28993419 5 36 gly glycosylation 956:968 arg2 sites 970:974 novel glycosylation sites 950:974 novel glycosylation sites dependent on the Ost3p and Ost6p regulatory subunits of OST 950:1034 We combined the method with genetic tools and validated the approach with the identification of novel glycosylation sites dependent on the Ost3p and Ost6p regulatory subunits of OST. 28993419 6 37 theme subunit 1257:1263 arg1 property 1231:1238 a direct property 1222:1238 a direct property of the catalytic subunit Stt3p 1222:1269 Based on the observations that alternations in LLO substrate structure and OST subunits activity differentially alter the systemic output of OST, we conclude that sequon recognition is a direct property of the catalytic subunit Stt3p, auxiliary subunits such as Ost3p and Ost6p extend the OST substrate range by modulating interfering pathways such as protein folding. 28993419 6 37 theme subunit 1257:1263 arg1 recognition 1207:1217 sequon recognition 1200:1217 sequon recognition 1200:1217 Based on the observations that alternations in LLO substrate structure and OST subunits activity differentially alter the systemic output of OST, we conclude that sequon recognition is a direct property of the catalytic subunit Stt3p, auxiliary subunits such as Ost3p and Ost6p extend the OST substrate range by modulating interfering pathways such as protein folding. 28993419 4 38 theme monitoring 813:822 arg1 MS 849:850 MS 849:850 MS 849:850 We developed a sensitive approach to examine glycosylation site occupancy in Saccharomyces cerevisiae by coupling stable isotope labeling (SILAC) approach to parallel reaction monitoring (PRM) mass spectrometry (MS). 28993419 4 38 theme monitoring 813:822 arg1 spectrometry 835:846 parallel reaction monitoring (PRM) mass spectrometry 795:846 parallel reaction monitoring (PRM) mass spectrometry (MS) 795:851 We developed a sensitive approach to examine glycosylation site occupancy in Saccharomyces cerevisiae by coupling stable isotope labeling (SILAC) approach to parallel reaction monitoring (PRM) mass spectrometry (MS). 28993419 1 39 theme proteins 234:241 arg1 structure 192:200 structure 192:200 structure 192:200 Asparagine-linked glycosylation is a common posttranslational protein modification regulating the structure, stability and function of many proteins. 28993419 1 39 theme proteins 234:241 arg1 function 217:224 function 217:224 function 217:224 Asparagine-linked glycosylation is a common posttranslational protein modification regulating the structure, stability and function of many proteins. 28993419 1 39 theme proteins 234:241 arg1 stability 203:211 stability 203:211 stability 203:211 Asparagine-linked glycosylation is a common posttranslational protein modification regulating the structure, stability and function of many proteins. 28993419 7 40 theme novel 1454:1458 arg1 network 1471:1477 a novel regulatory network 1452:1477 a novel regulatory network that connects isoprenoid lipid biosynthesis and LLO substrate assembly 1452:1548 In addition, our proteomics approach revealed a novel regulatory network that connects isoprenoid lipid biosynthesis and LLO substrate assembly. 28993419 6 41 theme direct 1224:1229 arg1 property 1231:1238 a direct property 1222:1238 a direct property of the catalytic subunit Stt3p 1222:1269 Based on the observations that alternations in LLO substrate structure and OST subunits activity differentially alter the systemic output of OST, we conclude that sequon recognition is a direct property of the catalytic subunit Stt3p, auxiliary subunits such as Ost3p and Ost6p extend the OST substrate range by modulating interfering pathways such as protein folding. 28993419 6 41 theme direct 1224:1229 arg1 recognition 1207:1217 sequon recognition 1200:1217 sequon recognition 1200:1217 Based on the observations that alternations in LLO substrate structure and OST subunits activity differentially alter the systemic output of OST, we conclude that sequon recognition is a direct property of the catalytic subunit Stt3p, auxiliary subunits such as Ost3p and Ost6p extend the OST substrate range by modulating interfering pathways such as protein folding. 28993419 1 42 theme common 131:136 arg1 modification 164:175 a common posttranslational protein modification 129:175 a common posttranslational protein modification regulating the structure, stability and function of many proteins 129:241 Asparagine-linked glycosylation is a common posttranslational protein modification regulating the structure, stability and function of many proteins. 28993419 1 42 theme common 131:136 arg1 glycosylation 112:124 Asparagine-linked glycosylation 94:124 Asparagine-linked glycosylation 94:124 Asparagine-linked glycosylation is a common posttranslational protein modification regulating the structure, stability and function of many proteins. 28993419 5 43 dep Ost3p 993:997 arg1 subunits 1020:1027 regulatory subunits 1009:1027 regulatory subunits of OST 1009:1034 We combined the method with genetic tools and validated the approach with the identification of novel glycosylation sites dependent on the Ost3p and Ost6p regulatory subunits of OST. 28993419 5 43 dep Ost3p 993:997 arg1 the 989:991 the 989:991 the 989:991 We combined the method with genetic tools and validated the approach with the identification of novel glycosylation sites dependent on the Ost3p and Ost6p regulatory subunits of OST. 28993419 0 44 theme Machinery 49:57 arg1 Profiling 13:21 Quantitative Profiling 0:21 Quantitative Profiling of N-linked Glycosylation Machinery in Yeast Saccharomyces cerevisiae 0:91 Quantitative Profiling of N-linked Glycosylation Machinery in Yeast Saccharomyces cerevisiae. 28993419 2 45 link lipid-linked 334:345 arg1 LLO 364:366 LLO 364:366 LLO 364:366 The N-linked glycosylation machinery involves enzymes responsible for the assembly of the lipid-linked oligosaccharide (LLO), which is then transferred to the asparagine residues on the polypeptides by the enzyme oligosaccharyltransferase (OST). 28993419 2 45 link lipid-linked 334:345 arg1 oligosaccharide 347:361 the lipid-linked oligosaccharide 330:361 the lipid-linked oligosaccharide (LLO) 330:367 The N-linked glycosylation machinery involves enzymes responsible for the assembly of the lipid-linked oligosaccharide (LLO), which is then transferred to the asparagine residues on the polypeptides by the enzyme oligosaccharyltransferase (OST). 28993419 6 46 theme interfering 1360:1370 arg1 folding 1397:1403 protein folding 1389:1403 protein folding 1389:1403 Based on the observations that alternations in LLO substrate structure and OST subunits activity differentially alter the systemic output of OST, we conclude that sequon recognition is a direct property of the catalytic subunit Stt3p, auxiliary subunits such as Ost3p and Ost6p extend the OST substrate range by modulating interfering pathways such as protein folding. 28993419 6 46 theme interfering 1360:1370 arg1 pathways 1372:1379 interfering pathways 1360:1379 interfering pathways such as protein folding 1360:1403 Based on the observations that alternations in LLO substrate structure and OST subunits activity differentially alter the systemic output of OST, we conclude that sequon recognition is a direct property of the catalytic subunit Stt3p, auxiliary subunits such as Ost3p and Ost6p extend the OST substrate range by modulating interfering pathways such as protein folding. 28993419 2 47 link N-linked 248:255 arg1 machinery 271:279 The N-linked glycosylation machinery 244:279 The N-linked glycosylation machinery 244:279 The N-linked glycosylation machinery involves enzymes responsible for the assembly of the lipid-linked oligosaccharide (LLO), which is then transferred to the asparagine residues on the polypeptides by the enzyme oligosaccharyltransferase (OST). 28993419 6 48 theme auxiliary 1272:1280 arg1 Ost6p 1309:1313 Ost6p 1309:1313 Ost6p 1309:1313 Based on the observations that alternations in LLO substrate structure and OST subunits activity differentially alter the systemic output of OST, we conclude that sequon recognition is a direct property of the catalytic subunit Stt3p, auxiliary subunits such as Ost3p and Ost6p extend the OST substrate range by modulating interfering pathways such as protein folding. 28993419 6 48 theme auxiliary 1272:1280 arg1 subunits 1282:1289 auxiliary subunits 1272:1289 auxiliary subunits such as Ost3p and Ost6p 1272:1313 Based on the observations that alternations in LLO substrate structure and OST subunits activity differentially alter the systemic output of OST, we conclude that sequon recognition is a direct property of the catalytic subunit Stt3p, auxiliary subunits such as Ost3p and Ost6p extend the OST substrate range by modulating interfering pathways such as protein folding. 28993419 6 48 theme auxiliary 1272:1280 arg1 Ost3p 1299:1303 Ost3p 1299:1303 Ost3p 1299:1303 Based on the observations that alternations in LLO substrate structure and OST subunits activity differentially alter the systemic output of OST, we conclude that sequon recognition is a direct property of the catalytic subunit Stt3p, auxiliary subunits such as Ost3p and Ost6p extend the OST substrate range by modulating interfering pathways such as protein folding. 28993419 2 49 theme enzyme 450:455 arg1 OST 484:486 OST 484:486 OST 484:486 The N-linked glycosylation machinery involves enzymes responsible for the assembly of the lipid-linked oligosaccharide (LLO), which is then transferred to the asparagine residues on the polypeptides by the enzyme oligosaccharyltransferase (OST). 28993419 2 49 theme enzyme 450:455 arg1 oligosaccharyltransferase 457:481 the enzyme oligosaccharyltransferase 446:481 the enzyme oligosaccharyltransferase (OST) 446:487 The N-linked glycosylation machinery involves enzymes responsible for the assembly of the lipid-linked oligosaccharide (LLO), which is then transferred to the asparagine residues on the polypeptides by the enzyme oligosaccharyltransferase (OST). 28993419 0 50 theme Glycosylation 35:47 arg1 Machinery 49:57 N-linked Glycosylation Machinery 26:57 N-linked Glycosylation Machinery 26:57 Quantitative Profiling of N-linked Glycosylation Machinery in Yeast Saccharomyces cerevisiae. 28993419 4 51 theme site 696:699 arg1 occupancy 701:709 glycosylation site occupancy 682:709 glycosylation site occupancy in Saccharomyces cerevisiae by coupling stable isotope labeling (SILAC) approach to parallel reaction monitoring (PRM) mass spectrometry (MS) 682:851 We developed a sensitive approach to examine glycosylation site occupancy in Saccharomyces cerevisiae by coupling stable isotope labeling (SILAC) approach to parallel reaction monitoring (PRM) mass spectrometry (MS). 28993419 0 52 theme Yeast 62:66 arg1 cerevisiae 82:91 Yeast Saccharomyces cerevisiae 62:91 Yeast Saccharomyces cerevisiae 62:91 Quantitative Profiling of N-linked Glycosylation Machinery in Yeast Saccharomyces cerevisiae. 28993419 6 53 theme systemic 1159:1166 arg1 output 1168:1173 the systemic output 1155:1173 the systemic output of OST 1155:1180 Based on the observations that alternations in LLO substrate structure and OST subunits activity differentially alter the systemic output of OST, we conclude that sequon recognition is a direct property of the catalytic subunit Stt3p, auxiliary subunits such as Ost3p and Ost6p extend the OST substrate range by modulating interfering pathways such as protein folding. 28993419 6 54 dep subunit 1257:1263 arg1 Stt3p 1265:1269 Stt3p 1265:1269 Stt3p 1265:1269 Based on the observations that alternations in LLO substrate structure and OST subunits activity differentially alter the systemic output of OST, we conclude that sequon recognition is a direct property of the catalytic subunit Stt3p, auxiliary subunits such as Ost3p and Ost6p extend the OST substrate range by modulating interfering pathways such as protein folding. 28993419 3 55 theme glycosylation 622:634 arg1 extent 612:617 site-specific extent 598:617 site-specific extent of glycosylation 598:634 A major goal in the study of protein glycosylation is to establish quantitative methods for the analysis of site-specific extent of glycosylation. 28993419 3 56 from goal 498:501 arg1 study 510:514 the study 506:514 the study of protein glycosylation 506:539 A major goal in the study of protein glycosylation is to establish quantitative methods for the analysis of site-specific extent of glycosylation. 28993419 1 57 theme posttranslational 138:154 arg1 modification 164:175 a common posttranslational protein modification 129:175 a common posttranslational protein modification regulating the structure, stability and function of many proteins 129:241 Asparagine-linked glycosylation is a common posttranslational protein modification regulating the structure, stability and function of many proteins. 28993419 1 57 theme posttranslational 138:154 arg1 glycosylation 112:124 Asparagine-linked glycosylation 94:124 Asparagine-linked glycosylation 94:124 Asparagine-linked glycosylation is a common posttranslational protein modification regulating the structure, stability and function of many proteins. 28993419 2 58 theme N-linked 248:255 arg1 machinery 271:279 The N-linked glycosylation machinery 244:279 The N-linked glycosylation machinery 244:279 The N-linked glycosylation machinery involves enzymes responsible for the assembly of the lipid-linked oligosaccharide (LLO), which is then transferred to the asparagine residues on the polypeptides by the enzyme oligosaccharyltransferase (OST). 28993419 2 59 theme glycosylation 257:269 arg1 machinery 271:279 The N-linked glycosylation machinery 244:279 The N-linked glycosylation machinery 244:279 The N-linked glycosylation machinery involves enzymes responsible for the assembly of the lipid-linked oligosaccharide (LLO), which is then transferred to the asparagine residues on the polypeptides by the enzyme oligosaccharyltransferase (OST). 28993419 1 60 theme protein 156:162 arg1 modification 164:175 a common posttranslational protein modification 129:175 a common posttranslational protein modification regulating the structure, stability and function of many proteins 129:241 Asparagine-linked glycosylation is a common posttranslational protein modification regulating the structure, stability and function of many proteins. 28993419 1 60 theme protein 156:162 arg1 glycosylation 112:124 Asparagine-linked glycosylation 94:124 Asparagine-linked glycosylation 94:124 Asparagine-linked glycosylation is a common posttranslational protein modification regulating the structure, stability and function of many proteins. 28993419 6 61 theme substrate 1330:1338 arg1 range 1340:1344 the OST substrate range 1322:1344 the OST substrate range 1322:1344 Based on the observations that alternations in LLO substrate structure and OST subunits activity differentially alter the systemic output of OST, we conclude that sequon recognition is a direct property of the catalytic subunit Stt3p, auxiliary subunits such as Ost3p and Ost6p extend the OST substrate range by modulating interfering pathways such as protein folding. 28993419 6 62 theme catalytic 1247:1255 arg1 subunit 1257:1263 the catalytic subunit Stt3p 1243:1269 the catalytic subunit Stt3p 1243:1269 Based on the observations that alternations in LLO substrate structure and OST subunits activity differentially alter the systemic output of OST, we conclude that sequon recognition is a direct property of the catalytic subunit Stt3p, auxiliary subunits such as Ost3p and Ost6p extend the OST substrate range by modulating interfering pathways such as protein folding. 28993419 5 63 theme OST 1032:1034 arg1 subunits 1020:1027 regulatory subunits 1009:1027 regulatory subunits of OST 1009:1034 We combined the method with genetic tools and validated the approach with the identification of novel glycosylation sites dependent on the Ost3p and Ost6p regulatory subunits of OST. 28993419 4 64 theme coupling 742:749 arg1 SILAC 776:780 SILAC 776:780 SILAC 776:780 We developed a sensitive approach to examine glycosylation site occupancy in Saccharomyces cerevisiae by coupling stable isotope labeling (SILAC) approach to parallel reaction monitoring (PRM) mass spectrometry (MS). 28993419 4 64 theme coupling 742:749 arg1 labeling 766:773 coupling stable isotope labeling 742:773 coupling stable isotope labeling (SILAC) approach to parallel reaction monitoring (PRM) mass spectrometry (MS) 742:851 We developed a sensitive approach to examine glycosylation site occupancy in Saccharomyces cerevisiae by coupling stable isotope labeling (SILAC) approach to parallel reaction monitoring (PRM) mass spectrometry (MS). 28993419 5 65 theme sites 970:974 arg1 identification 932:945 the identification 928:945 the identification of novel glycosylation sites dependent on the Ost3p and Ost6p regulatory subunits of OST 928:1034 We combined the method with genetic tools and validated the approach with the identification of novel glycosylation sites dependent on the Ost3p and Ost6p regulatory subunits of OST. 28993419 7 66 theme proteomics 1423:1432 arg1 approach 1434:1441 our proteomics approach 1419:1441 our proteomics approach 1419:1441 In addition, our proteomics approach revealed a novel regulatory network that connects isoprenoid lipid biosynthesis and LLO substrate assembly. 28993419 4 67 theme sensitive 652:660 arg1 approach 662:669 a sensitive approach 650:669 a sensitive approach to examine glycosylation site occupancy in Saccharomyces cerevisiae by coupling stable isotope labeling (SILAC) approach to parallel reaction monitoring (PRM) mass spectrometry (MS) 650:851 We developed a sensitive approach to examine glycosylation site occupancy in Saccharomyces cerevisiae by coupling stable isotope labeling (SILAC) approach to parallel reaction monitoring (PRM) mass spectrometry (MS). 28993419 6 68 theme OST 1326:1328 arg1 range 1340:1344 the OST substrate range 1322:1344 the OST substrate range 1322:1344 Based on the observations that alternations in LLO substrate structure and OST subunits activity differentially alter the systemic output of OST, we conclude that sequon recognition is a direct property of the catalytic subunit Stt3p, auxiliary subunits such as Ost3p and Ost6p extend the OST substrate range by modulating interfering pathways such as protein folding. 28993419 5 69 theme novel 950:954 arg1 sites 970:974 novel glycosylation sites 950:974 novel glycosylation sites dependent on the Ost3p and Ost6p regulatory subunits of OST 950:1034 We combined the method with genetic tools and validated the approach with the identification of novel glycosylation sites dependent on the Ost3p and Ost6p regulatory subunits of OST. 28993419 4 70 theme PRM 825:827 arg1 MS 849:850 MS 849:850 MS 849:850 We developed a sensitive approach to examine glycosylation site occupancy in Saccharomyces cerevisiae by coupling stable isotope labeling (SILAC) approach to parallel reaction monitoring (PRM) mass spectrometry (MS). 28993419 4 70 theme PRM 825:827 arg1 spectrometry 835:846 parallel reaction monitoring (PRM) mass spectrometry 795:846 parallel reaction monitoring (PRM) mass spectrometry (MS) 795:851 We developed a sensitive approach to examine glycosylation site occupancy in Saccharomyces cerevisiae by coupling stable isotope labeling (SILAC) approach to parallel reaction monitoring (PRM) mass spectrometry (MS). 28993419 4 71 theme reaction 804:811 arg1 MS 849:850 MS 849:850 MS 849:850 We developed a sensitive approach to examine glycosylation site occupancy in Saccharomyces cerevisiae by coupling stable isotope labeling (SILAC) approach to parallel reaction monitoring (PRM) mass spectrometry (MS). 28993419 4 71 theme reaction 804:811 arg1 spectrometry 835:846 parallel reaction monitoring (PRM) mass spectrometry 795:846 parallel reaction monitoring (PRM) mass spectrometry (MS) 795:851 We developed a sensitive approach to examine glycosylation site occupancy in Saccharomyces cerevisiae by coupling stable isotope labeling (SILAC) approach to parallel reaction monitoring (PRM) mass spectrometry (MS). 28993419 3 72 theme quantitative 557:568 arg1 methods 570:576 quantitative methods 557:576 quantitative methods for the analysis of site-specific extent of glycosylation 557:634 A major goal in the study of protein glycosylation is to establish quantitative methods for the analysis of site-specific extent of glycosylation. 28993419 3 73 theme major 492:496 arg1 goal 498:501 A major goal 490:501 A major goal in the study of protein glycosylation 490:539 A major goal in the study of protein glycosylation is to establish quantitative methods for the analysis of site-specific extent of glycosylation. 28993419 4 74 theme glycosylation 682:694 arg1 occupancy 701:709 glycosylation site occupancy 682:709 glycosylation site occupancy in Saccharomyces cerevisiae by coupling stable isotope labeling (SILAC) approach to parallel reaction monitoring (PRM) mass spectrometry (MS) 682:851 We developed a sensitive approach to examine glycosylation site occupancy in Saccharomyces cerevisiae by coupling stable isotope labeling (SILAC) approach to parallel reaction monitoring (PRM) mass spectrometry (MS). 28993419 4 75 theme stable 751:756 arg1 SILAC 776:780 SILAC 776:780 SILAC 776:780 We developed a sensitive approach to examine glycosylation site occupancy in Saccharomyces cerevisiae by coupling stable isotope labeling (SILAC) approach to parallel reaction monitoring (PRM) mass spectrometry (MS). 28993419 4 75 theme stable 751:756 arg1 labeling 766:773 coupling stable isotope labeling 742:773 coupling stable isotope labeling (SILAC) approach to parallel reaction monitoring (PRM) mass spectrometry (MS) 742:851 We developed a sensitive approach to examine glycosylation site occupancy in Saccharomyces cerevisiae by coupling stable isotope labeling (SILAC) approach to parallel reaction monitoring (PRM) mass spectrometry (MS). 28993419 6 76 dep property 1231:1238 arg1 extend 1315:1320 extend 1315:1320 extend the OST substrate range by modulating interfering pathways such as protein folding 1315:1403 Based on the observations that alternations in LLO substrate structure and OST subunits activity differentially alter the systemic output of OST, we conclude that sequon recognition is a direct property of the catalytic subunit Stt3p, auxiliary subunits such as Ost3p and Ost6p extend the OST substrate range by modulating interfering pathways such as protein folding. 28993419 0 77 theme Saccharomyces 68:80 arg1 cerevisiae 82:91 Yeast Saccharomyces cerevisiae 62:91 Yeast Saccharomyces cerevisiae 62:91 Quantitative Profiling of N-linked Glycosylation Machinery in Yeast Saccharomyces cerevisiae. 28993419 7 78 theme substrate 1531:1539 arg1 assembly 1541:1548 LLO substrate assembly 1527:1548 LLO substrate assembly 1527:1548 In addition, our proteomics approach revealed a novel regulatory network that connects isoprenoid lipid biosynthesis and LLO substrate assembly. 28993419 2 79 theme responsible 298:308 arg1 enzymes 290:296 enzymes 290:296 enzymes responsible for the assembly of the lipid-linked oligosaccharide (LLO), which is then transferred to the asparagine residues on the polypeptides by the enzyme oligosaccharyltransferase (OST) 290:487 The N-linked glycosylation machinery involves enzymes responsible for the assembly of the lipid-linked oligosaccharide (LLO), which is then transferred to the asparagine residues on the polypeptides by the enzyme oligosaccharyltransferase (OST). 28993419 2 80 theme asparagine 403:412 arg1 residues 414:421 the asparagine residues 399:421 the asparagine residues on the polypeptides 399:441 The N-linked glycosylation machinery involves enzymes responsible for the assembly of the lipid-linked oligosaccharide (LLO), which is then transferred to the asparagine residues on the polypeptides by the enzyme oligosaccharyltransferase (OST). 28993419 3 81 theme glycosylation 527:539 arg1 study 510:514 the study 506:514 the study of protein glycosylation 506:539 A major goal in the study of protein glycosylation is to establish quantitative methods for the analysis of site-specific extent of glycosylation. 28993419 6 82 theme LLO 1084:1086 arg1 activity 1125:1132 LLO substrate structure and OST subunits activity 1084:1132 LLO substrate structure and OST subunits activity 1084:1132 Based on the observations that alternations in LLO substrate structure and OST subunits activity differentially alter the systemic output of OST, we conclude that sequon recognition is a direct property of the catalytic subunit Stt3p, auxiliary subunits such as Ost3p and Ost6p extend the OST substrate range by modulating interfering pathways such as protein folding. 25388861 9 0 theme N-linked 1246:1253 arg1 glycosylation 1255:1267 N-linked glycosylation 1246:1267 N-linked glycosylation 1246:1267 N-linked glycosylation occurs at the consensus pattern Asn-Xaa-Ser/Thr; with Thr at i + 2, the sequence can adopt the secondary structure of a ω-turn, which may be the recognition site for protein modification. 25388861 10 1 theme common 1500:1505 arg1 occurrence 1507:1516 the most common occurrence 1491:1516 the most common occurrence in protein tertiary structure 1491:1546 Location between two β-strands is the most common occurrence in protein tertiary structure, and being generally exposed ω-turn may constitute the antigenic determinant site. 25388861 10 1 theme common 1500:1505 arg1 Location 1457:1464 Location 1457:1464 Location between two β-strands 1457:1486 Location between two β-strands is the most common occurrence in protein tertiary structure, and being generally exposed ω-turn may constitute the antigenic determinant site. 25388861 8 2 theme metal-binding 1225:1237 arg1 sites 1239:1243 the metal-binding sites 1221:1243 the metal-binding sites 1221:1243 With Cys occupying the i + 1 position, such turns are found in the metal-binding sites. 25388861 11 3 theme peptide 1698:1704 arg1 design 1706:1711 peptide design 1698:1711 peptide design 1698:1711 It is a stable scaffold and may be used in protein engineering and peptide design. 25388861 1 4 theme common 144:149 arg1 feature 151:157 a common feature 142:157 a common feature in proteins 142:169 Mimicry of structural motifs is a common feature in proteins. 25388861 1 4 theme common 144:149 arg1 Mimicry 110:116 Mimicry 110:116 Mimicry of structural motifs 110:137 Mimicry of structural motifs is a common feature in proteins. 25388861 0 5 theme side-chain 78:87 arg1 interaction 97:107 side-chain C−H···O interaction 78:107 side-chain C−H···O interaction 78:107 ω-Turn: a novel β-turn mimic in globular proteins stabilized by main-chain to side-chain C−H···O interaction. 25388861 7 6 theme last 1028:1031 arg1 residues 1037:1044 the last two residues 1024:1044 the last two residues 1024:1044 C(β) -branched side-chains, and Met and Gln have high propensities to occur at i + 2; for the last two residues the carbonyl oxygen may participate in an additional interaction involving the S and amino group, respectively. 25388861 11 7 used used 1666:1669 arg2 It 1631:1632 It 1631:1632 It 1631:1632 It is a stable scaffold and may be used in protein engineering and peptide design. 25388861 11 7 used used 1666:1669 arg2 scaffold 1646:1653 a stable scaffold 1637:1653 a stable scaffold 1637:1653 It is a stable scaffold and may be used in protein engineering and peptide design. 25388861 3 8 theme H···O 462:466 arg1 interaction 468:478 a nonconventional C − H···O interaction 440:478 a nonconventional C − H···O interaction 440:478 We show that the N − H component of hydrogen bond can be replaced by a C(γ) -H group in the side chain, culminating in a nonconventional C − H···O interaction. 25388861 10 9 theme protein 1521:1527 arg1 structure 1538:1546 protein tertiary structure 1521:1546 protein tertiary structure 1521:1546 Location between two β-strands is the most common occurrence in protein tertiary structure, and being generally exposed ω-turn may constitute the antigenic determinant site. 25388861 4 10 dep β-turn 507:512 arg1 mimic 514:518 mimic 514:518 mimic 514:518 Because of its shape this β-turn mimic is designated as ω-turn, which is found to occur ∼ three times per 100 residues. 25388861 8 11 located found 1212:1216 arg2 turns 1202:1206 such turns 1197:1206 such turns 1197:1206 With Cys occupying the i + 1 position, such turns are found in the metal-binding sites. 25388861 8 11 located found 1212:1216 arg1 sites 1239:1243 the metal-binding sites 1221:1243 the metal-binding sites 1221:1243 With Cys occupying the i + 1 position, such turns are found in the metal-binding sites. 25388861 3 12 theme nonconventional 442:456 arg1 interaction 468:478 a nonconventional C − H···O interaction 440:478 a nonconventional C − H···O interaction 440:478 We show that the N − H component of hydrogen bond can be replaced by a C(γ) -H group in the side chain, culminating in a nonconventional C − H···O interaction. 25388861 10 13 theme determinant 1613:1623 arg1 site 1625:1628 the antigenic determinant site 1599:1628 the antigenic determinant site 1599:1628 Location between two β-strands is the most common occurrence in protein tertiary structure, and being generally exposed ω-turn may constitute the antigenic determinant site. 25388861 10 14 from occurrence 1507:1516 arg1 structure 1538:1546 protein tertiary structure 1521:1546 protein tertiary structure 1521:1546 Location between two β-strands is the most common occurrence in protein tertiary structure, and being generally exposed ω-turn may constitute the antigenic determinant site. 25388861 7 15 theme C 934:934 arg1 side-chains 949:959 C(β) -branched side-chains, and Met and Gln 934:976 side-chains 949:959 C(β) -branched side-chains, and Met and Gln have high propensities to occur at i + 2; for the last two residues the carbonyl oxygen may participate in an additional interaction involving the S and amino group, respectively. 25388861 5 16 theme H···O 662:666 arg1 interaction 668:678 the C − H···O interaction 654:678 the C − H···O interaction 654:678 Three residues (i to i + 2) constitute the turn with the C − H···O interaction occurring between the terminal residues, constraining the torsion angles ϕi + 1, ψi + 1, ϕi + 2 and χ'1(i + 2) (using the interacting C(γ) atom). 25388861 5 17 dep angles 746:751 arg1 using 792:796 using 792:796 using the interacting C(γ) atom 792:822 Three residues (i to i + 2) constitute the turn with the C − H···O interaction occurring between the terminal residues, constraining the torsion angles ϕi + 1, ψi + 1, ϕi + 2 and χ'1(i + 2) (using the interacting C(γ) atom). 25388861 5 17 dep angles 746:751 arg1 ϕi 753:754 ϕi 753:754 ϕi 753:754 Three residues (i to i + 2) constitute the turn with the C − H···O interaction occurring between the terminal residues, constraining the torsion angles ϕi + 1, ψi + 1, ϕi + 2 and χ'1(i + 2) (using the interacting C(γ) atom). 25388861 5 17 dep angles 746:751 arg1 1 766:766 1 766:766 1 766:766 Three residues (i to i + 2) constitute the turn with the C − H···O interaction occurring between the terminal residues, constraining the torsion angles ϕi + 1, ψi + 1, ϕi + 2 and χ'1(i + 2) (using the interacting C(γ) atom). 25388861 5 17 dep angles 746:751 arg1 χ 780:780 χ 780:780 χ 780:780 Three residues (i to i + 2) constitute the turn with the C − H···O interaction occurring between the terminal residues, constraining the torsion angles ϕi + 1, ψi + 1, ϕi + 2 and χ'1(i + 2) (using the interacting C(γ) atom). 25388861 5 17 dep angles 746:751 arg1 1 758:758 1 758:758 1 758:758 Three residues (i to i + 2) constitute the turn with the C − H···O interaction occurring between the terminal residues, constraining the torsion angles ϕi + 1, ψi + 1, ϕi + 2 and χ'1(i + 2) (using the interacting C(γ) atom). 25388861 9 18 theme ω-turn 1389:1394 arg1 structure 1374:1382 the secondary structure 1360:1382 the secondary structure of a ω-turn, which may be the recognition site for protein modification 1360:1454 N-linked glycosylation occurs at the consensus pattern Asn-Xaa-Ser/Thr; with Thr at i + 2, the sequence can adopt the secondary structure of a ω-turn, which may be the recognition site for protein modification. 25388861 7 19 theme high 983:986 arg1 propensities 988:999 high propensities 983:999 high propensities 983:999 C(β) -branched side-chains, and Met and Gln have high propensities to occur at i + 2; for the last two residues the carbonyl oxygen may participate in an additional interaction involving the S and amino group, respectively. 25388861 0 20 theme C−H···O 89:95 arg1 interaction 97:107 side-chain C−H···O interaction 78:107 side-chain C−H···O interaction 78:107 ω-Turn: a novel β-turn mimic in globular proteins stabilized by main-chain to side-chain C−H···O interaction. 25388861 5 21 theme torsion 738:744 arg1 angles 746:751 the torsion angles ϕi + 1, ψi + 1, ϕi + 2 and χ'1(i + 2) 734:789 the torsion angles ϕi + 1, ψi + 1, ϕi + 2 and χ'1(i + 2) (using the interacting C(γ) atom) 734:823 Three residues (i to i + 2) constitute the turn with the C − H···O interaction occurring between the terminal residues, constraining the torsion angles ϕi + 1, ψi + 1, ϕi + 2 and χ'1(i + 2) (using the interacting C(γ) atom). 25388861 9 22 theme consensus 1283:1291 arg1 Asn-Xaa-Ser/Thr 1301:1315 the consensus pattern Asn-Xaa-Ser/Thr 1279:1315 the consensus pattern Asn-Xaa-Ser/Thr 1279:1315 N-linked glycosylation occurs at the consensus pattern Asn-Xaa-Ser/Thr; with Thr at i + 2, the sequence can adopt the secondary structure of a ω-turn, which may be the recognition site for protein modification. 25388861 5 23 dep ϕi 753:754 arg1 i 784:784 i 784:784 i 784:784 Three residues (i to i + 2) constitute the turn with the C − H···O interaction occurring between the terminal residues, constraining the torsion angles ϕi + 1, ψi + 1, ϕi + 2 and χ'1(i + 2) (using the interacting C(γ) atom). 25388861 5 23 dep ϕi 753:754 arg1 1 782:782 1 782:782 1 782:782 Three residues (i to i + 2) constitute the turn with the C − H···O interaction occurring between the terminal residues, constraining the torsion angles ϕi + 1, ψi + 1, ϕi + 2 and χ'1(i + 2) (using the interacting C(γ) atom). 25388861 5 23 dep ϕi 753:754 arg1 2 788:788 2 788:788 2 788:788 Three residues (i to i + 2) constitute the turn with the C − H···O interaction occurring between the terminal residues, constraining the torsion angles ϕi + 1, ψi + 1, ϕi + 2 and χ'1(i + 2) (using the interacting C(γ) atom). 25388861 3 24 theme − 340:340 arg1 component 344:352 the N − H component 334:352 the N − H component of hydrogen bond 334:369 We show that the N − H component of hydrogen bond can be replaced by a C(γ) -H group in the side chain, culminating in a nonconventional C − H···O interaction. 25388861 8 25 theme i 1181:1181 arg1 position 1187:1194 the i + 1 position 1177:1194 the i + 1 position 1177:1194 With Cys occupying the i + 1 position, such turns are found in the metal-binding sites. 25388861 9 26 theme pattern 1293:1299 arg1 Asn-Xaa-Ser/Thr 1301:1315 the consensus pattern Asn-Xaa-Ser/Thr 1279:1315 the consensus pattern Asn-Xaa-Ser/Thr 1279:1315 N-linked glycosylation occurs at the consensus pattern Asn-Xaa-Ser/Thr; with Thr at i + 2, the sequence can adopt the secondary structure of a ω-turn, which may be the recognition site for protein modification. 25388861 2 27 theme carbonyl 285:292 arg1 group 294:298 a side-chain carbonyl group 272:298 a side-chain carbonyl group leading to Asx-turn 272:318 The 10-membered hydrogen-bonded ring involving the main-chain C − O in a β-turn can be formed using a side-chain carbonyl group leading to Asx-turn. 25388861 7 28 theme additional 1088:1097 arg1 interaction 1099:1109 an additional interaction 1085:1109 an additional interaction involving the S and amino group, respectively 1085:1155 C(β) -branched side-chains, and Met and Gln have high propensities to occur at i + 2; for the last two residues the carbonyl oxygen may participate in an additional interaction involving the S and amino group, respectively. 25388861 5 29 theme terminal 702:709 arg1 residues 711:718 the terminal residues 698:718 the terminal residues 698:718 Three residues (i to i + 2) constitute the turn with the C − H···O interaction occurring between the terminal residues, constraining the torsion angles ϕi + 1, ψi + 1, ϕi + 2 and χ'1(i + 2) (using the interacting C(γ) atom). 25388861 3 30 theme H 342:342 arg1 component 344:352 the N − H component 334:352 the N − H component of hydrogen bond 334:369 We show that the N − H component of hydrogen bond can be replaced by a C(γ) -H group in the side chain, culminating in a nonconventional C − H···O interaction. 25388861 10 31 theme tertiary 1529:1536 arg1 structure 1538:1546 protein tertiary structure 1521:1546 protein tertiary structure 1521:1546 Location between two β-strands is the most common occurrence in protein tertiary structure, and being generally exposed ω-turn may constitute the antigenic determinant site. 25388861 3 32 from group 400:404 arg1 chain 418:422 the side chain 409:422 the side chain 409:422 We show that the N − H component of hydrogen bond can be replaced by a C(γ) -H group in the side chain, culminating in a nonconventional C − H···O interaction. 25388861 2 33 theme side-chain 274:283 arg1 group 294:298 a side-chain carbonyl group 272:298 a side-chain carbonyl group leading to Asx-turn 272:318 The 10-membered hydrogen-bonded ring involving the main-chain C − O in a β-turn can be formed using a side-chain carbonyl group leading to Asx-turn. 25388861 0 34 theme novel 10:14 arg1 β-turn 16:21 a novel β-turn 8:21 ω-Turn: a novel β-turn mimic in globular proteins stabilized by main-chain to side-chain C−H···O interaction. 0:108 ω-Turn: a novel β-turn mimic in globular proteins stabilized by main-chain to side-chain C−H···O interaction. 25388861 5 35 dep i 622:622 arg1 to 619:620 to 619:620 to 619:620 Three residues (i to i + 2) constitute the turn with the C − H···O interaction occurring between the terminal residues, constraining the torsion angles ϕi + 1, ψi + 1, ϕi + 2 and χ'1(i + 2) (using the interacting C(γ) atom). 25388861 3 36 theme C 458:458 arg1 interaction 468:478 a nonconventional C − H···O interaction 440:478 a nonconventional C − H···O interaction 440:478 We show that the N − H component of hydrogen bond can be replaced by a C(γ) -H group in the side chain, culminating in a nonconventional C − H···O interaction. 25388861 5 37 theme − 660:660 arg1 interaction 668:678 the C − H···O interaction 654:678 the C − H···O interaction 654:678 Three residues (i to i + 2) constitute the turn with the C − H···O interaction occurring between the terminal residues, constraining the torsion angles ϕi + 1, ψi + 1, ϕi + 2 and χ'1(i + 2) (using the interacting C(γ) atom). 25388861 3 38 theme N 338:338 arg1 component 344:352 the N − H component 334:352 the N − H component of hydrogen bond 334:369 We show that the N − H component of hydrogen bond can be replaced by a C(γ) -H group in the side chain, culminating in a nonconventional C − H···O interaction. 25388861 6 39 theme ω-turns 871:877 arg1 types 862:866 two types 858:866 two types 858:866 Based on these angles there are two types of ω-turns, each of which can be further divided into two groups. 25388861 5 40 theme interacting 802:812 arg1 atom 819:822 the interacting C(γ) atom 798:822 the interacting C(γ) atom 798:822 Three residues (i to i + 2) constitute the turn with the C − H···O interaction occurring between the terminal residues, constraining the torsion angles ϕi + 1, ψi + 1, ϕi + 2 and χ'1(i + 2) (using the interacting C(γ) atom). 25388861 3 41 theme − 460:460 arg1 interaction 468:478 a nonconventional C − H···O interaction 440:478 a nonconventional C − H···O interaction 440:478 We show that the N − H component of hydrogen bond can be replaced by a C(γ) -H group in the side chain, culminating in a nonconventional C − H···O interaction. 25388861 3 42 theme γ 394:394 arg1 group 400:404 a C(γ) -H group 390:404 a C(γ) -H group 390:404 We show that the N − H component of hydrogen bond can be replaced by a C(γ) -H group in the side chain, culminating in a nonconventional C − H···O interaction. 25388861 3 43 theme hydrogen 357:364 arg1 bond 366:369 hydrogen bond 357:369 hydrogen bond 357:369 We show that the N − H component of hydrogen bond can be replaced by a C(γ) -H group in the side chain, culminating in a nonconventional C − H···O interaction. 25388861 7 44 dep S 1125:1125 arg1 the 1121:1123 the 1121:1123 the 1121:1123 C(β) -branched side-chains, and Met and Gln have high propensities to occur at i + 2; for the last two residues the carbonyl oxygen may participate in an additional interaction involving the S and amino group, respectively. 25388861 5 45 theme C 814:814 arg1 atom 819:822 the interacting C(γ) atom 798:822 the interacting C(γ) atom 798:822 Three residues (i to i + 2) constitute the turn with the C − H···O interaction occurring between the terminal residues, constraining the torsion angles ϕi + 1, ψi + 1, ϕi + 2 and χ'1(i + 2) (using the interacting C(γ) atom). 25388861 2 46 theme C 234:234 arg1 O 238:238 the main-chain C − O 219:238 the main-chain C − O 219:238 The 10-membered hydrogen-bonded ring involving the main-chain C − O in a β-turn can be formed using a side-chain carbonyl group leading to Asx-turn. 25388861 9 47 link N-linked 1246:1253 arg1 glycosylation 1255:1267 N-linked glycosylation 1246:1267 N-linked glycosylation 1246:1267 N-linked glycosylation occurs at the consensus pattern Asn-Xaa-Ser/Thr; with Thr at i + 2, the sequence can adopt the secondary structure of a ω-turn, which may be the recognition site for protein modification. 25388861 3 48 theme bond 366:369 arg1 component 344:352 the N − H component 334:352 the N − H component of hydrogen bond 334:369 We show that the N − H component of hydrogen bond can be replaced by a C(γ) -H group in the side chain, culminating in a nonconventional C − H···O interaction. 25388861 2 49 theme main-chain 223:232 arg1 O 238:238 the main-chain C − O 219:238 the main-chain C − O 219:238 The 10-membered hydrogen-bonded ring involving the main-chain C − O in a β-turn can be formed using a side-chain carbonyl group leading to Asx-turn. 25388861 10 50 theme being 1553:1557 arg1 ω-turn 1577:1582 being generally exposed ω-turn 1553:1582 being generally exposed ω-turn 1553:1582 Location between two β-strands is the most common occurrence in protein tertiary structure, and being generally exposed ω-turn may constitute the antigenic determinant site. 25388861 3 51 theme C 392:392 arg1 group 400:404 a C(γ) -H group 390:404 a C(γ) -H group 390:404 We show that the N − H component of hydrogen bond can be replaced by a C(γ) -H group in the side chain, culminating in a nonconventional C − H···O interaction. 25388861 0 52 theme globular 32:39 arg1 proteins 41:48 globular proteins 32:48 globular proteins stabilized by main-chain to side-chain C−H···O interaction 32:107 ω-Turn: a novel β-turn mimic in globular proteins stabilized by main-chain to side-chain C−H···O interaction. 25388861 8 53 theme 1 1185:1185 arg1 position 1187:1194 the i + 1 position 1177:1194 the i + 1 position 1177:1194 With Cys occupying the i + 1 position, such turns are found in the metal-binding sites. 25388861 11 54 theme protein 1674:1680 arg1 engineering 1682:1692 protein engineering 1674:1692 protein engineering 1674:1692 It is a stable scaffold and may be used in protein engineering and peptide design. 25388861 7 55 theme -branched 939:947 arg1 side-chains 949:959 C(β) -branched side-chains, and Met and Gln 934:976 side-chains 949:959 C(β) -branched side-chains, and Met and Gln have high propensities to occur at i + 2; for the last two residues the carbonyl oxygen may participate in an additional interaction involving the S and amino group, respectively. 25388861 9 56 theme recognition 1414:1424 arg1 site 1426:1429 the recognition site 1410:1429 the recognition site for protein modification 1410:1454 N-linked glycosylation occurs at the consensus pattern Asn-Xaa-Ser/Thr; with Thr at i + 2, the sequence can adopt the secondary structure of a ω-turn, which may be the recognition site for protein modification. 25388861 9 56 theme recognition 1414:1424 arg1 ω-turn 1389:1394 a ω-turn 1387:1394 a ω-turn 1387:1394 N-linked glycosylation occurs at the consensus pattern Asn-Xaa-Ser/Thr; with Thr at i + 2, the sequence can adopt the secondary structure of a ω-turn, which may be the recognition site for protein modification. 25388861 8 57 theme such 1197:1200 arg1 turns 1202:1206 such turns 1197:1206 such turns 1197:1206 With Cys occupying the i + 1 position, such turns are found in the metal-binding sites. 25388861 11 58 theme stable 1639:1644 arg1 scaffold 1646:1653 a stable scaffold 1637:1653 a stable scaffold 1637:1653 It is a stable scaffold and may be used in protein engineering and peptide design. 25388861 11 58 theme stable 1639:1644 arg1 It 1631:1632 It 1631:1632 It 1631:1632 It is a stable scaffold and may be used in protein engineering and peptide design. 25388861 7 59 contain have 978:981 arg2 propensities 988:999 high propensities 983:999 high propensities 983:999 C(β) -branched side-chains, and Met and Gln have high propensities to occur at i + 2; for the last two residues the carbonyl oxygen may participate in an additional interaction involving the S and amino group, respectively. 25388861 7 59 contain have 978:981 arg1 Met 966:968 Met 966:968 Met 966:968 C(β) -branched side-chains, and Met and Gln have high propensities to occur at i + 2; for the last two residues the carbonyl oxygen may participate in an additional interaction involving the S and amino group, respectively. 25388861 7 59 contain have 978:981 arg1 side-chains 949:959 C(β) -branched side-chains, and Met and Gln 934:976 side-chains 949:959 C(β) -branched side-chains, and Met and Gln have high propensities to occur at i + 2; for the last two residues the carbonyl oxygen may participate in an additional interaction involving the S and amino group, respectively. 25388861 0 60 dep β-turn 16:21 arg1 mimic 23:27 mimic 23:27 mimic in globular proteins stabilized by main-chain to side-chain C−H···O interaction 23:107 ω-Turn: a novel β-turn mimic in globular proteins stabilized by main-chain to side-chain C−H···O interaction. 25388861 3 61 theme side 413:416 arg1 chain 418:422 the side chain 409:422 the side chain 409:422 We show that the N − H component of hydrogen bond can be replaced by a C(γ) -H group in the side chain, culminating in a nonconventional C − H···O interaction. 25388861 9 62 gly glycosylation 1255:1267 arg2 Asn-Xaa-Ser/Thr 1301:1315 the consensus pattern Asn-Xaa-Ser/Thr 1279:1315 the consensus pattern Asn-Xaa-Ser/Thr 1279:1315 N-linked glycosylation occurs at the consensus pattern Asn-Xaa-Ser/Thr; with Thr at i + 2, the sequence can adopt the secondary structure of a ω-turn, which may be the recognition site for protein modification. 25388861 0 63 dep ω-Turn 0:5 arg1 β-turn 16:21 a novel β-turn 8:21 ω-Turn: a novel β-turn mimic in globular proteins stabilized by main-chain to side-chain C−H···O interaction. 0:108 ω-Turn: a novel β-turn mimic in globular proteins stabilized by main-chain to side-chain C−H···O interaction. 25388861 2 64 theme hydrogen-bonded 188:202 arg1 ring 204:207 The 10-membered hydrogen-bonded ring 172:207 The 10-membered hydrogen-bonded ring involving the main-chain C − O in a β-turn 172:250 The 10-membered hydrogen-bonded ring involving the main-chain C − O in a β-turn can be formed using a side-chain carbonyl group leading to Asx-turn. 25388861 10 65 theme exposed 1569:1575 arg1 ω-turn 1577:1582 being generally exposed ω-turn 1553:1582 being generally exposed ω-turn 1553:1582 Location between two β-strands is the most common occurrence in protein tertiary structure, and being generally exposed ω-turn may constitute the antigenic determinant site. 25388861 5 66 dep residues 711:718 arg1 constraining 721:732 constraining 721:732 constraining the torsion angles ϕi + 1, ψi + 1, ϕi + 2 and χ'1(i + 2) (using the interacting C(γ) atom) 721:823 Three residues (i to i + 2) constitute the turn with the C − H···O interaction occurring between the terminal residues, constraining the torsion angles ϕi + 1, ψi + 1, ϕi + 2 and χ'1(i + 2) (using the interacting C(γ) atom). 25388861 7 67 theme β 936:936 arg1 side-chains 949:959 C(β) -branched side-chains, and Met and Gln 934:976 side-chains 949:959 C(β) -branched side-chains, and Met and Gln have high propensities to occur at i + 2; for the last two residues the carbonyl oxygen may participate in an additional interaction involving the S and amino group, respectively. 25388861 9 68 from 2 1334:1334 arg1 Thr 1323:1325 Thr 1323:1325 Thr at i + 2 1323:1334 N-linked glycosylation occurs at the consensus pattern Asn-Xaa-Ser/Thr; with Thr at i + 2, the sequence can adopt the secondary structure of a ω-turn, which may be the recognition site for protein modification. 25388861 7 69 theme carbonyl 1050:1057 arg1 oxygen 1059:1064 the carbonyl oxygen 1046:1064 the carbonyl oxygen 1046:1064 C(β) -branched side-chains, and Met and Gln have high propensities to occur at i + 2; for the last two residues the carbonyl oxygen may participate in an additional interaction involving the S and amino group, respectively. 25388861 2 70 theme 10-membered 176:186 arg1 ring 204:207 The 10-membered hydrogen-bonded ring 172:207 The 10-membered hydrogen-bonded ring involving the main-chain C − O in a β-turn 172:250 The 10-membered hydrogen-bonded ring involving the main-chain C − O in a β-turn can be formed using a side-chain carbonyl group leading to Asx-turn. 25388861 5 71 theme C 658:658 arg1 interaction 668:678 the C − H···O interaction 654:678 the C − H···O interaction 654:678 Three residues (i to i + 2) constitute the turn with the C − H···O interaction occurring between the terminal residues, constraining the torsion angles ϕi + 1, ψi + 1, ϕi + 2 and χ'1(i + 2) (using the interacting C(γ) atom). 25388861 1 72 theme structural 121:130 arg1 motifs 132:137 structural motifs 121:137 structural motifs 121:137 Mimicry of structural motifs is a common feature in proteins. 25388861 9 73 theme protein 1435:1441 arg1 modification 1443:1454 protein modification 1435:1454 protein modification 1435:1454 N-linked glycosylation occurs at the consensus pattern Asn-Xaa-Ser/Thr; with Thr at i + 2, the sequence can adopt the secondary structure of a ω-turn, which may be the recognition site for protein modification. 25388861 7 74 theme amino 1131:1135 arg1 group 1137:1141 amino group 1131:1141 amino group 1131:1141 C(β) -branched side-chains, and Met and Gln have high propensities to occur at i + 2; for the last two residues the carbonyl oxygen may participate in an additional interaction involving the S and amino group, respectively. 25388861 1 75 theme motifs 132:137 arg1 feature 151:157 a common feature 142:157 a common feature in proteins 142:169 Mimicry of structural motifs is a common feature in proteins. 25388861 1 75 theme motifs 132:137 arg1 Mimicry 110:116 Mimicry 110:116 Mimicry of structural motifs 110:137 Mimicry of structural motifs is a common feature in proteins. 25388861 9 76 from i 1330:1330 arg1 Thr 1323:1325 Thr 1323:1325 Thr at i + 2 1323:1334 N-linked glycosylation occurs at the consensus pattern Asn-Xaa-Ser/Thr; with Thr at i + 2, the sequence can adopt the secondary structure of a ω-turn, which may be the recognition site for protein modification. 25388861 2 77 theme − 236:236 arg1 O 238:238 the main-chain C − O 219:238 the main-chain C − O 219:238 The 10-membered hydrogen-bonded ring involving the main-chain C − O in a β-turn can be formed using a side-chain carbonyl group leading to Asx-turn. 25388861 1 78 from feature 151:157 arg1 proteins 162:169 proteins 162:169 proteins 162:169 Mimicry of structural motifs is a common feature in proteins. 25388861 10 79 theme antigenic 1603:1611 arg1 site 1625:1628 the antigenic determinant site 1599:1628 the antigenic determinant site 1599:1628 Location between two β-strands is the most common occurrence in protein tertiary structure, and being generally exposed ω-turn may constitute the antigenic determinant site. 25388861 9 80 theme secondary 1364:1372 arg1 structure 1374:1382 the secondary structure 1360:1382 the secondary structure of a ω-turn, which may be the recognition site for protein modification 1360:1454 N-linked glycosylation occurs at the consensus pattern Asn-Xaa-Ser/Thr; with Thr at i + 2, the sequence can adopt the secondary structure of a ω-turn, which may be the recognition site for protein modification. 28280844 6 0 theme informative 1286:1296 arg1 fragments 1346:1354 highly informative, mostly C- and Z-type glycosidic and cross-ring fragments 1279:1354 highly informative, mostly C- and Z-type glycosidic and cross-ring fragments 1279:1354 Data-dependent MS2 in negative mode provides highly informative, mostly C- and Z-type glycosidic and cross-ring fragments, making software-assisted and manual annotation reliable. 28280844 4 1 theme novel 905:909 arg1 desalter 911:918 a novel desalter 903:918 a novel desalter 903:918 With the relatively high flow rate of HPAE-PAD, post-column splitting diverted 60% of the flow to a novel desalter, then to the mass spectrometer. 28280844 5 2 theme positional 1118:1127 arg1 isomers 1129:1135 positional isomers 1118:1135 positional isomers 1118:1135 The delay between PAD and MS detectors is consistent, and salt removal after the column supports MS. HPAE resolves sialylated (charged) glycans and their linkage and positional isomers very well; separations of neutral glycans are sufficient for highly reproducible glycoprofiling. 28280844 1 3 theme present 195:201 arg1 glycans 187:193 glycans 187:193 glycans present on glycoproteins 187:218 Characterization of glycans present on glycoproteins has become of increasing importance due to their biological implications, such as protein folding, immunogenicity, cell-cell adhesion, clearance, receptor interactions, etc. 28280844 4 4 theme flow 830:833 arg1 rate 835:838 the relatively high flow rate 810:838 the relatively high flow rate of HPAE-PAD 810:850 With the relatively high flow rate of HPAE-PAD, post-column splitting diverted 60% of the flow to a novel desalter, then to the mass spectrometer. 28280844 5 5 theme reproducible 1205:1216 arg1 glycoprofiling 1218:1231 highly reproducible glycoprofiling 1198:1231 highly reproducible glycoprofiling 1198:1231 The delay between PAD and MS detectors is consistent, and salt removal after the column supports MS. HPAE resolves sialylated (charged) glycans and their linkage and positional isomers very well; separations of neutral glycans are sufficient for highly reproducible glycoprofiling. 28280844 6 6 theme software-assisted 1364:1380 arg1 annotation 1393:1402 software-assisted and manual annotation 1364:1402 software-assisted and manual annotation 1364:1402 Data-dependent MS2 in negative mode provides highly informative, mostly C- and Z-type glycosidic and cross-ring fragments, making software-assisted and manual annotation reliable. 28280844 1 7 gly glycoproteins 206:218 arg1 glycoproteins 206:218 glycoproteins 206:218 glycoproteins 206:218 Characterization of glycans present on glycoproteins has become of increasing importance due to their biological implications, such as protein folding, immunogenicity, cell-cell adhesion, clearance, receptor interactions, etc. 28280844 5 8 dep PAD 970:972 arg1 detectors 981:989 detectors 981:989 detectors 981:989 The delay between PAD and MS detectors is consistent, and salt removal after the column supports MS. HPAE resolves sialylated (charged) glycans and their linkage and positional isomers very well; separations of neutral glycans are sufficient for highly reproducible glycoprofiling. 28280844 6 9 theme Z-type 1313:1318 arg1 fragments 1346:1354 highly informative, mostly C- and Z-type glycosidic and cross-ring fragments 1279:1354 highly informative, mostly C- and Z-type glycosidic and cross-ring fragments 1279:1354 Data-dependent MS2 in negative mode provides highly informative, mostly C- and Z-type glycosidic and cross-ring fragments, making software-assisted and manual annotation reliable. 28280844 3 10 theme reproducible 754:765 arg1 annotation 767:776 reliable and reproducible annotation 741:776 reliable and reproducible annotation 741:776 A new, rapid workflow generates glycans from 200 μg of glycoprotein supporting reliable and reproducible annotation by mass spectrometry (MS). 28280844 6 11 theme C- 1306:1307 arg1 fragments 1346:1354 highly informative, mostly C- and Z-type glycosidic and cross-ring fragments 1279:1354 highly informative, mostly C- and Z-type glycosidic and cross-ring fragments 1279:1354 Data-dependent MS2 in negative mode provides highly informative, mostly C- and Z-type glycosidic and cross-ring fragments, making software-assisted and manual annotation reliable. 28280844 4 12 theme high 825:828 arg1 rate 835:838 the relatively high flow rate 810:838 the relatively high flow rate of HPAE-PAD 810:850 With the relatively high flow rate of HPAE-PAD, post-column splitting diverted 60% of the flow to a novel desalter, then to the mass spectrometer. 28280844 5 13 gly sialylated 1067:1076 arg1 glycans 1088:1094 sialylated (charged) glycans 1067:1094 sialylated (charged) glycans 1067:1094 The delay between PAD and MS detectors is consistent, and salt removal after the column supports MS. HPAE resolves sialylated (charged) glycans and their linkage and positional isomers very well; separations of neutral glycans are sufficient for highly reproducible glycoprofiling. 28280844 1 14 theme protein 302:308 arg1 clearance 355:363 clearance 355:363 clearance 355:363 Characterization of glycans present on glycoproteins has become of increasing importance due to their biological implications, such as protein folding, immunogenicity, cell-cell adhesion, clearance, receptor interactions, etc. 28280844 1 14 theme protein 302:308 arg1 immunogenicity 319:332 immunogenicity 319:332 immunogenicity 319:332 Characterization of glycans present on glycoproteins has become of increasing importance due to their biological implications, such as protein folding, immunogenicity, cell-cell adhesion, clearance, receptor interactions, etc. 28280844 1 14 theme protein 302:308 arg1 interactions 375:386 receptor interactions 366:386 receptor interactions 366:386 Characterization of glycans present on glycoproteins has become of increasing importance due to their biological implications, such as protein folding, immunogenicity, cell-cell adhesion, clearance, receptor interactions, etc. 28280844 1 14 theme protein 302:308 arg1 etc 389:391 etc 389:391 etc 389:391 Characterization of glycans present on glycoproteins has become of increasing importance due to their biological implications, such as protein folding, immunogenicity, cell-cell adhesion, clearance, receptor interactions, etc. 28280844 1 14 theme protein 302:308 arg1 adhesion 345:352 cell-cell adhesion 335:352 cell-cell adhesion 335:352 Characterization of glycans present on glycoproteins has become of increasing importance due to their biological implications, such as protein folding, immunogenicity, cell-cell adhesion, clearance, receptor interactions, etc. 28280844 1 14 theme protein 302:308 arg1 folding 310:316 protein folding 302:316 protein folding 302:316 Characterization of glycans present on glycoproteins has become of increasing importance due to their biological implications, such as protein folding, immunogenicity, cell-cell adhesion, clearance, receptor interactions, etc. 28280844 0 15 theme amperometric 114:125 arg1 detection 127:135 amperometric detection 114:135 amperometric detection coupled to mass spectrometry 114:164 In-depth analyses of native N-linked glycans facilitated by high-performance anion exchange chromatography-pulsed amperometric detection coupled to mass spectrometry. 28280844 2 16 theme different 637:645 arg1 glycoproteins 647:659 different glycoproteins 637:659 different glycoproteins 637:659 In this study, the resolving power of high-performance anion exchange chromatography with pulsed amperometric detection (HPAE-PAD) was applied to glycan separations and coupled to mass spectrometry to characterize native glycans released from different glycoproteins. 28280844 2 17 attach released 623:630 arg2 glycans 615:621 native glycans 608:621 native glycans released from different glycoproteins 608:659 In this study, the resolving power of high-performance anion exchange chromatography with pulsed amperometric detection (HPAE-PAD) was applied to glycan separations and coupled to mass spectrometry to characterize native glycans released from different glycoproteins. 28280844 2 17 attach released 623:630 arg1 glycoproteins 647:659 different glycoproteins 637:659 different glycoproteins 637:659 In this study, the resolving power of high-performance anion exchange chromatography with pulsed amperometric detection (HPAE-PAD) was applied to glycan separations and coupled to mass spectrometry to characterize native glycans released from different glycoproteins. 28280844 8 18 theme structures 1633:1642 arg1 characterization 1606:1621 characterization 1606:1621 characterization of 17 new structures from glycoproteins with challenging glycan profiles 1606:1694 Combining the isomer resolution of HPAE with MS2 permitted thorough N-glycan annotation and led to characterization of 17 new structures from glycoproteins with challenging glycan profiles. 28280844 7 19 theme MS-based 1485:1492 arg1 annotations 1494:1504 MS-based annotations 1485:1504 MS-based annotations 1485:1504 Fractionation of glycans followed by exoglycosidase digestion confirms MS-based annotations. 28280844 3 20 from 200 μg 707:712 arg1 glycans 694:700 glycans 694:700 glycans from 200 μg of glycoprotein supporting reliable and reproducible annotation by mass spectrometry (MS) 694:802 A new, rapid workflow generates glycans from 200 μg of glycoprotein supporting reliable and reproducible annotation by mass spectrometry (MS). 28280844 3 21 theme mass 781:784 arg1 spectrometry 786:797 mass spectrometry 781:797 mass spectrometry (MS) 781:802 A new, rapid workflow generates glycans from 200 μg of glycoprotein supporting reliable and reproducible annotation by mass spectrometry (MS). 28280844 3 21 theme mass 781:784 arg1 MS 800:801 MS 800:801 MS 800:801 A new, rapid workflow generates glycans from 200 μg of glycoprotein supporting reliable and reproducible annotation by mass spectrometry (MS). 28280844 6 22 theme manual 1386:1391 arg1 annotation 1393:1402 software-assisted and manual annotation 1364:1402 software-assisted and manual annotation 1364:1402 Data-dependent MS2 in negative mode provides highly informative, mostly C- and Z-type glycosidic and cross-ring fragments, making software-assisted and manual annotation reliable. 28280844 8 23 from glycoproteins 1649:1661 arg1 structures 1633:1642 17 new structures 1626:1642 17 new structures from glycoproteins with challenging glycan profiles 1626:1694 Combining the isomer resolution of HPAE with MS2 permitted thorough N-glycan annotation and led to characterization of 17 new structures from glycoproteins with challenging glycan profiles. 28280844 8 23 from glycoproteins 1649:1661 arg1 characterization 1606:1621 characterization 1606:1621 characterization of 17 new structures from glycoproteins with challenging glycan profiles 1606:1694 Combining the isomer resolution of HPAE with MS2 permitted thorough N-glycan annotation and led to characterization of 17 new structures from glycoproteins with challenging glycan profiles. 28280844 2 24 theme pulsed 484:489 arg1 HPAE-PAD 515:522 HPAE-PAD 515:522 HPAE-PAD 515:522 In this study, the resolving power of high-performance anion exchange chromatography with pulsed amperometric detection (HPAE-PAD) was applied to glycan separations and coupled to mass spectrometry to characterize native glycans released from different glycoproteins. 28280844 2 24 theme pulsed 484:489 arg1 detection 504:512 pulsed amperometric detection 484:512 pulsed amperometric detection (HPAE-PAD) 484:523 In this study, the resolving power of high-performance anion exchange chromatography with pulsed amperometric detection (HPAE-PAD) was applied to glycan separations and coupled to mass spectrometry to characterize native glycans released from different glycoproteins. 28280844 2 25 theme resolving 413:421 arg1 power 423:427 the resolving power 409:427 the resolving power of high-performance anion exchange chromatography with pulsed amperometric detection (HPAE-PAD) 409:523 In this study, the resolving power of high-performance anion exchange chromatography with pulsed amperometric detection (HPAE-PAD) was applied to glycan separations and coupled to mass spectrometry to characterize native glycans released from different glycoproteins. 28280844 2 26 theme amperometric 491:502 arg1 HPAE-PAD 515:522 HPAE-PAD 515:522 HPAE-PAD 515:522 In this study, the resolving power of high-performance anion exchange chromatography with pulsed amperometric detection (HPAE-PAD) was applied to glycan separations and coupled to mass spectrometry to characterize native glycans released from different glycoproteins. 28280844 2 26 theme amperometric 491:502 arg1 detection 504:512 pulsed amperometric detection 484:512 pulsed amperometric detection (HPAE-PAD) 484:523 In this study, the resolving power of high-performance anion exchange chromatography with pulsed amperometric detection (HPAE-PAD) was applied to glycan separations and coupled to mass spectrometry to characterize native glycans released from different glycoproteins. 28280844 1 27 attach present 195:201 arg2 glycans 187:193 glycans 187:193 glycans present on glycoproteins 187:218 Characterization of glycans present on glycoproteins has become of increasing importance due to their biological implications, such as protein folding, immunogenicity, cell-cell adhesion, clearance, receptor interactions, etc. 28280844 1 27 attach present 195:201 arg1 glycoproteins 206:218 glycoproteins 206:218 glycoproteins 206:218 Characterization of glycans present on glycoproteins has become of increasing importance due to their biological implications, such as protein folding, immunogenicity, cell-cell adhesion, clearance, receptor interactions, etc. 28280844 8 28 theme glycan 1680:1685 arg1 profiles 1687:1694 challenging glycan profiles 1668:1694 challenging glycan profiles 1668:1694 Combining the isomer resolution of HPAE with MS2 permitted thorough N-glycan annotation and led to characterization of 17 new structures from glycoproteins with challenging glycan profiles. 28280844 2 29 theme glycan 540:545 arg1 separations 547:557 glycan separations 540:557 glycan separations 540:557 In this study, the resolving power of high-performance anion exchange chromatography with pulsed amperometric detection (HPAE-PAD) was applied to glycan separations and coupled to mass spectrometry to characterize native glycans released from different glycoproteins. 28280844 6 30 theme glycosidic 1320:1329 arg1 fragments 1346:1354 highly informative, mostly C- and Z-type glycosidic and cross-ring fragments 1279:1354 highly informative, mostly C- and Z-type glycosidic and cross-ring fragments 1279:1354 Data-dependent MS2 in negative mode provides highly informative, mostly C- and Z-type glycosidic and cross-ring fragments, making software-assisted and manual annotation reliable. 28280844 0 31 theme In-depth 0:7 arg1 analyses 9:16 In-depth analyses 0:16 In-depth analyses of native N-linked glycans facilitated by high-performance anion exchange 0:90 In-depth analyses of native N-linked glycans facilitated by high-performance anion exchange chromatography-pulsed amperometric detection coupled to mass spectrometry. 28280844 8 32 theme new 1629:1631 arg1 structures 1633:1642 17 new structures 1626:1642 17 new structures from glycoproteins with challenging glycan profiles 1626:1694 Combining the isomer resolution of HPAE with MS2 permitted thorough N-glycan annotation and led to characterization of 17 new structures from glycoproteins with challenging glycan profiles. 28280844 4 33 theme flow 895:898 arg1 flow 895:898 the flow 891:898 the flow 891:898 With the relatively high flow rate of HPAE-PAD, post-column splitting diverted 60% of the flow to a novel desalter, then to the mass spectrometer. 28280844 4 33 theme flow 895:898 arg1 % 886:886 60% 884:886 60% of the flow 884:898 With the relatively high flow rate of HPAE-PAD, post-column splitting diverted 60% of the flow to a novel desalter, then to the mass spectrometer. 28280844 0 34 theme native 21:26 arg1 glycans 37:43 native N-linked glycans 21:43 native N-linked glycans facilitated by high-performance anion exchange 21:90 In-depth analyses of native N-linked glycans facilitated by high-performance anion exchange chromatography-pulsed amperometric detection coupled to mass spectrometry. 28280844 0 35 link N-linked 28:35 arg1 glycans 37:43 native N-linked glycans 21:43 native N-linked glycans facilitated by high-performance anion exchange 21:90 In-depth analyses of native N-linked glycans facilitated by high-performance anion exchange chromatography-pulsed amperometric detection coupled to mass spectrometry. 28280844 8 36 theme N-glycan 1575:1582 arg1 annotation 1584:1593 thorough N-glycan annotation 1566:1593 thorough N-glycan annotation 1566:1593 Combining the isomer resolution of HPAE with MS2 permitted thorough N-glycan annotation and led to characterization of 17 new structures from glycoproteins with challenging glycan profiles. 28280844 2 37 theme exchange 455:462 arg1 chromatography 464:477 high-performance anion exchange chromatography 432:477 high-performance anion exchange chromatography with pulsed amperometric detection (HPAE-PAD) 432:523 In this study, the resolving power of high-performance anion exchange chromatography with pulsed amperometric detection (HPAE-PAD) was applied to glycan separations and coupled to mass spectrometry to characterize native glycans released from different glycoproteins. 28280844 2 38 theme chromatography 464:477 arg1 power 423:427 the resolving power 409:427 the resolving power of high-performance anion exchange chromatography with pulsed amperometric detection (HPAE-PAD) 409:523 In this study, the resolving power of high-performance anion exchange chromatography with pulsed amperometric detection (HPAE-PAD) was applied to glycan separations and coupled to mass spectrometry to characterize native glycans released from different glycoproteins. 28280844 0 39 theme mass 148:151 arg1 spectrometry 153:164 mass spectrometry 148:164 mass spectrometry 148:164 In-depth analyses of native N-linked glycans facilitated by high-performance anion exchange chromatography-pulsed amperometric detection coupled to mass spectrometry. 28280844 5 40 theme charged 1079:1085 arg1 glycans 1088:1094 sialylated (charged) glycans 1067:1094 sialylated (charged) glycans 1067:1094 The delay between PAD and MS detectors is consistent, and salt removal after the column supports MS. HPAE resolves sialylated (charged) glycans and their linkage and positional isomers very well; separations of neutral glycans are sufficient for highly reproducible glycoprofiling. 28280844 7 41 theme exoglycosidase 1451:1464 arg1 digestion 1466:1474 exoglycosidase digestion 1451:1474 exoglycosidase digestion 1451:1474 Fractionation of glycans followed by exoglycosidase digestion confirms MS-based annotations. 28280844 2 42 theme anion 449:453 arg1 chromatography 464:477 high-performance anion exchange chromatography 432:477 high-performance anion exchange chromatography with pulsed amperometric detection (HPAE-PAD) 432:523 In this study, the resolving power of high-performance anion exchange chromatography with pulsed amperometric detection (HPAE-PAD) was applied to glycan separations and coupled to mass spectrometry to characterize native glycans released from different glycoproteins. 28280844 0 43 theme glycans 37:43 arg1 analyses 9:16 In-depth analyses 0:16 In-depth analyses of native N-linked glycans facilitated by high-performance anion exchange 0:90 In-depth analyses of native N-linked glycans facilitated by high-performance anion exchange chromatography-pulsed amperometric detection coupled to mass spectrometry. 28280844 1 44 theme cell-cell 335:343 arg1 adhesion 345:352 cell-cell adhesion 335:352 cell-cell adhesion 335:352 Characterization of glycans present on glycoproteins has become of increasing importance due to their biological implications, such as protein folding, immunogenicity, cell-cell adhesion, clearance, receptor interactions, etc. 28280844 1 44 theme cell-cell 335:343 arg1 folding 310:316 protein folding 302:316 protein folding 302:316 Characterization of glycans present on glycoproteins has become of increasing importance due to their biological implications, such as protein folding, immunogenicity, cell-cell adhesion, clearance, receptor interactions, etc. 28280844 7 45 theme glycans 1431:1437 arg1 Fractionation 1414:1426 Fractionation 1414:1426 Fractionation of glycans followed by exoglycosidase digestion 1414:1474 Fractionation of glycans followed by exoglycosidase digestion confirms MS-based annotations. 28280844 2 46 theme high-performance 432:447 arg1 chromatography 464:477 high-performance anion exchange chromatography 432:477 high-performance anion exchange chromatography with pulsed amperometric detection (HPAE-PAD) 432:523 In this study, the resolving power of high-performance anion exchange chromatography with pulsed amperometric detection (HPAE-PAD) was applied to glycan separations and coupled to mass spectrometry to characterize native glycans released from different glycoproteins. 28280844 0 47 theme N-linked 28:35 arg1 glycans 37:43 native N-linked glycans 21:43 native N-linked glycans facilitated by high-performance anion exchange 21:90 In-depth analyses of native N-linked glycans facilitated by high-performance anion exchange chromatography-pulsed amperometric detection coupled to mass spectrometry. 28280844 2 48 theme mass 574:577 arg1 spectrometry 579:590 mass spectrometry 574:590 mass spectrometry 574:590 In this study, the resolving power of high-performance anion exchange chromatography with pulsed amperometric detection (HPAE-PAD) was applied to glycan separations and coupled to mass spectrometry to characterize native glycans released from different glycoproteins. 28280844 6 49 theme negative 1256:1263 arg1 mode 1265:1268 negative mode 1256:1268 negative mode 1256:1268 Data-dependent MS2 in negative mode provides highly informative, mostly C- and Z-type glycosidic and cross-ring fragments, making software-assisted and manual annotation reliable. 28280844 8 50 theme isomer 1521:1526 arg1 resolution 1528:1537 the isomer resolution 1517:1537 the isomer resolution of HPAE 1517:1545 Combining the isomer resolution of HPAE with MS2 permitted thorough N-glycan annotation and led to characterization of 17 new structures from glycoproteins with challenging glycan profiles. 28280844 2 51 gly glycoproteins 647:659 arg1 glycoproteins 647:659 different glycoproteins 637:659 different glycoproteins 637:659 In this study, the resolving power of high-performance anion exchange chromatography with pulsed amperometric detection (HPAE-PAD) was applied to glycan separations and coupled to mass spectrometry to characterize native glycans released from different glycoproteins. 28280844 8 52 theme thorough 1566:1573 arg1 annotation 1584:1593 thorough N-glycan annotation 1566:1593 thorough N-glycan annotation 1566:1593 Combining the isomer resolution of HPAE with MS2 permitted thorough N-glycan annotation and led to characterization of 17 new structures from glycoproteins with challenging glycan profiles. 28280844 2 53 with chromatography 464:477 arg1 HPAE-PAD 515:522 HPAE-PAD 515:522 HPAE-PAD 515:522 In this study, the resolving power of high-performance anion exchange chromatography with pulsed amperometric detection (HPAE-PAD) was applied to glycan separations and coupled to mass spectrometry to characterize native glycans released from different glycoproteins. 28280844 2 53 with chromatography 464:477 arg1 detection 504:512 pulsed amperometric detection 484:512 pulsed amperometric detection (HPAE-PAD) 484:523 In this study, the resolving power of high-performance anion exchange chromatography with pulsed amperometric detection (HPAE-PAD) was applied to glycan separations and coupled to mass spectrometry to characterize native glycans released from different glycoproteins. 28280844 8 54 from characterization 1606:1621 arg1 glycoproteins 1649:1661 glycoproteins 1649:1661 glycoproteins with challenging glycan profiles 1649:1694 Combining the isomer resolution of HPAE with MS2 permitted thorough N-glycan annotation and led to characterization of 17 new structures from glycoproteins with challenging glycan profiles. 28280844 5 55 theme neutral 1163:1169 arg1 glycans 1171:1177 neutral glycans 1163:1177 neutral glycans 1163:1177 The delay between PAD and MS detectors is consistent, and salt removal after the column supports MS. HPAE resolves sialylated (charged) glycans and their linkage and positional isomers very well; separations of neutral glycans are sufficient for highly reproducible glycoprofiling. 28280844 6 56 theme cross-ring 1335:1344 arg1 fragments 1346:1354 highly informative, mostly C- and Z-type glycosidic and cross-ring fragments 1279:1354 highly informative, mostly C- and Z-type glycosidic and cross-ring fragments 1279:1354 Data-dependent MS2 in negative mode provides highly informative, mostly C- and Z-type glycosidic and cross-ring fragments, making software-assisted and manual annotation reliable. 28280844 6 57 theme Data-dependent 1234:1247 arg1 MS2 1249:1251 Data-dependent MS2 1234:1251 Data-dependent MS2 in negative mode 1234:1268 Data-dependent MS2 in negative mode provides highly informative, mostly C- and Z-type glycosidic and cross-ring fragments, making software-assisted and manual annotation reliable. 28280844 5 58 theme MS. 1049:1051 arg1 HPAE 1053:1056 MS. HPAE 1049:1056 MS. HPAE resolves sialylated (charged) glycans and their linkage and positional isomers 1049:1135 The delay between PAD and MS detectors is consistent, and salt removal after the column supports MS. HPAE resolves sialylated (charged) glycans and their linkage and positional isomers very well; separations of neutral glycans are sufficient for highly reproducible glycoprofiling. 28280844 8 59 theme challenging 1668:1678 arg1 profiles 1687:1694 challenging glycan profiles 1668:1694 challenging glycan profiles 1668:1694 Combining the isomer resolution of HPAE with MS2 permitted thorough N-glycan annotation and led to characterization of 17 new structures from glycoproteins with challenging glycan profiles. 28280844 5 60 theme glycans 1171:1177 arg1 separations 1148:1158 separations 1148:1158 separations of neutral glycans 1148:1177 The delay between PAD and MS detectors is consistent, and salt removal after the column supports MS. HPAE resolves sialylated (charged) glycans and their linkage and positional isomers very well; separations of neutral glycans are sufficient for highly reproducible glycoprofiling. 28280844 4 61 theme mass 933:936 arg1 spectrometer 938:949 the mass spectrometer 929:949 the mass spectrometer 929:949 With the relatively high flow rate of HPAE-PAD, post-column splitting diverted 60% of the flow to a novel desalter, then to the mass spectrometer. 28280844 3 62 theme reliable 741:748 arg1 annotation 767:776 reliable and reproducible annotation 741:776 reliable and reproducible annotation 741:776 A new, rapid workflow generates glycans from 200 μg of glycoprotein supporting reliable and reproducible annotation by mass spectrometry (MS). 28280844 4 63 theme HPAE-PAD 843:850 arg1 rate 835:838 the relatively high flow rate 810:838 the relatively high flow rate of HPAE-PAD 810:850 With the relatively high flow rate of HPAE-PAD, post-column splitting diverted 60% of the flow to a novel desalter, then to the mass spectrometer. 28280844 6 64 from MS2 1249:1251 arg1 mode 1265:1268 negative mode 1256:1268 negative mode 1256:1268 Data-dependent MS2 in negative mode provides highly informative, mostly C- and Z-type glycosidic and cross-ring fragments, making software-assisted and manual annotation reliable. 28280844 2 65 theme native 608:613 arg1 glycans 615:621 native glycans 608:621 native glycans released from different glycoproteins 608:659 In this study, the resolving power of high-performance anion exchange chromatography with pulsed amperometric detection (HPAE-PAD) was applied to glycan separations and coupled to mass spectrometry to characterize native glycans released from different glycoproteins. 28280844 1 66 dep such 294:297 arg1 as 299:300 as 299:300 as 299:300 Characterization of glycans present on glycoproteins has become of increasing importance due to their biological implications, such as protein folding, immunogenicity, cell-cell adhesion, clearance, receptor interactions, etc. 28280844 5 67 theme salt 1010:1013 arg1 removal 1015:1021 salt removal 1010:1021 salt removal after the column 1010:1038 The delay between PAD and MS detectors is consistent, and salt removal after the column supports MS. HPAE resolves sialylated (charged) glycans and their linkage and positional isomers very well; separations of neutral glycans are sufficient for highly reproducible glycoprofiling. 28280844 8 68 theme HPAE 1542:1545 arg1 resolution 1528:1537 the isomer resolution 1517:1537 the isomer resolution of HPAE 1517:1545 Combining the isomer resolution of HPAE with MS2 permitted thorough N-glycan annotation and led to characterization of 17 new structures from glycoproteins with challenging glycan profiles. 28280844 5 69 theme sialylated 1067:1076 arg1 glycans 1088:1094 sialylated (charged) glycans 1067:1094 sialylated (charged) glycans 1067:1094 The delay between PAD and MS detectors is consistent, and salt removal after the column supports MS. HPAE resolves sialylated (charged) glycans and their linkage and positional isomers very well; separations of neutral glycans are sufficient for highly reproducible glycoprofiling. 28280844 1 70 theme biological 269:278 arg1 implications 280:291 their biological implications 263:291 their biological implications 263:291 Characterization of glycans present on glycoproteins has become of increasing importance due to their biological implications, such as protein folding, immunogenicity, cell-cell adhesion, clearance, receptor interactions, etc. 28280844 0 71 theme anion 77:81 arg1 exchange 83:90 high-performance anion exchange 60:90 high-performance anion exchange 60:90 In-depth analyses of native N-linked glycans facilitated by high-performance anion exchange chromatography-pulsed amperometric detection coupled to mass spectrometry. 28280844 3 72 theme glycoprotein 717:728 arg1 200 μg 707:712 200 μg 707:712 200 μg of glycoprotein supporting reliable and reproducible annotation by mass spectrometry (MS) 707:802 A new, rapid workflow generates glycans from 200 μg of glycoprotein supporting reliable and reproducible annotation by mass spectrometry (MS). 28280844 3 73 theme new 664:666 arg1 workflow 675:682 A new, rapid workflow 662:682 A new, rapid workflow 662:682 A new, rapid workflow generates glycans from 200 μg of glycoprotein supporting reliable and reproducible annotation by mass spectrometry (MS). 28280844 3 74 dep new 664:666 arg1 rapid 669:673 rapid 669:673 rapid 669:673 A new, rapid workflow generates glycans from 200 μg of glycoprotein supporting reliable and reproducible annotation by mass spectrometry (MS). 28280844 8 75 gly glycoproteins 1649:1661 arg1 glycoproteins 1649:1661 glycoproteins 1649:1661 glycoproteins with challenging glycan profiles 1649:1694 Combining the isomer resolution of HPAE with MS2 permitted thorough N-glycan annotation and led to characterization of 17 new structures from glycoproteins with challenging glycan profiles. 28280844 3 76 gly glycoprotein 717:728 arg1 glycoprotein 717:728 glycoprotein 717:728 glycoprotein supporting reliable and reproducible annotation by mass spectrometry (MS) 717:802 A new, rapid workflow generates glycans from 200 μg of glycoprotein supporting reliable and reproducible annotation by mass spectrometry (MS). 28280844 0 77 theme high-performance 60:75 arg1 exchange 83:90 high-performance anion exchange 60:90 high-performance anion exchange 60:90 In-depth analyses of native N-linked glycans facilitated by high-performance anion exchange chromatography-pulsed amperometric detection coupled to mass spectrometry. 28280844 1 78 theme receptor 366:373 arg1 interactions 375:386 receptor interactions 366:386 receptor interactions 366:386 Characterization of glycans present on glycoproteins has become of increasing importance due to their biological implications, such as protein folding, immunogenicity, cell-cell adhesion, clearance, receptor interactions, etc. 28280844 1 78 theme receptor 366:373 arg1 folding 310:316 protein folding 302:316 protein folding 302:316 Characterization of glycans present on glycoproteins has become of increasing importance due to their biological implications, such as protein folding, immunogenicity, cell-cell adhesion, clearance, receptor interactions, etc. 28280844 8 79 with glycoproteins 1649:1661 arg1 profiles 1687:1694 challenging glycan profiles 1668:1694 challenging glycan profiles 1668:1694 Combining the isomer resolution of HPAE with MS2 permitted thorough N-glycan annotation and led to characterization of 17 new structures from glycoproteins with challenging glycan profiles. 28280844 1 80 theme glycans 187:193 arg1 Characterization 167:182 Characterization 167:182 Characterization of glycans present on glycoproteins 167:218 Characterization of glycans present on glycoproteins has become of increasing importance due to their biological implications, such as protein folding, immunogenicity, cell-cell adhesion, clearance, receptor interactions, etc. 28280844 5 81 dep HPAE 1053:1056 arg1 resolves 1058:1065 resolves 1058:1065 resolves sialylated (charged) glycans and their linkage and positional isomers 1058:1135 The delay between PAD and MS detectors is consistent, and salt removal after the column supports MS. HPAE resolves sialylated (charged) glycans and their linkage and positional isomers very well; separations of neutral glycans are sufficient for highly reproducible glycoprofiling. 27757071 11 0 theme protein 2039:2045 arg1 clue 2070:2073 a clue 2068:2073 a clue to dissimilarities in T1DM and T2DM 2068:2109 Thus, N-glycosylated protein differences could be a clue to dissimilarities in T1DM and T2DM at later stages of DN. 27757071 11 0 theme protein 2039:2045 arg1 differences 2047:2057 N-glycosylated protein differences 2024:2057 N-glycosylated protein differences 2024:2057 Thus, N-glycosylated protein differences could be a clue to dissimilarities in T1DM and T2DM at later stages of DN. 27757071 10 1 theme STZ 1872:1874 arg1 models 1882:1887 the db/db and STZ mouse models 1858:1887 models 1882:1887 CONCLUSIONS Our finding of differences in the N-glycosylation protein profiles in the db/db and STZ mouse models suggest that the etiology of DN could give rise to variations in the cell adhesion and cell-matrix composition in T1DM and T2DM. 27757071 2 2 theme extracellular 307:319 arg1 matrix 321:326 the extracellular matrix 303:326 the extracellular matrix where the majority of the proteins carry N-linked glycosylations 303:391 Already at an early stage of DN morphological changes occur at the cell surface and in the extracellular matrix where the majority of the proteins carry N-linked glycosylations. 27757071 7 3 theme proximal 1401:1408 arg1 tubules 1410:1416 the proximal tubules 1397:1416 the proximal tubules which abundance was increased in the db/db mice but decreased in the STZ diabetic mice 1397:1503 However, distinct differences between the two mouse models were for example seen for integrin-β1, a protein expressed mainly in the glomeruli which abundance was increased in the STZ diabetic mice while decreased in the db/db mice and for the sodium/glucose cotransporter-1, mainly expressed in the proximal tubules which abundance was increased in the db/db mice but decreased in the STZ diabetic mice. 27757071 8 4 theme db/db 1588:1592 arg1 mice 1594:1597 the db/db mice 1584:1597 the db/db mice 1584:1597 Insulin had an effect on the level of both glomerular and tubular proteins in the db/db mice. 27757071 2 5 theme morphological 248:260 arg1 changes 262:268 DN morphological changes 245:268 DN morphological changes 245:268 Already at an early stage of DN morphological changes occur at the cell surface and in the extracellular matrix where the majority of the proteins carry N-linked glycosylations. 27757071 4 6 theme healthy 781:787 arg1 mice 797:800 healthy control mice 781:800 healthy control mice dosed with vehicle 781:819 METHOD We enriched for the N-glycosylated kidney proteome in db/db mice dosed with insulin or vehicle, in streptozotocin-induced (STZ) diabetic mice and healthy control mice dosed with vehicle. 27757071 6 7 theme proteins 1046:1053 arg1 majority 1015:1022 The majority 1011:1022 RESULTS The majority of the N-glycosylated proteins 1003:1053 RESULTS The majority of the N-glycosylated proteins were similarly regulated in both mouse models. 27757071 8 8 from level 1535:1539 arg1 mice 1594:1597 the db/db mice 1584:1597 the db/db mice 1584:1597 Insulin had an effect on the level of both glomerular and tubular proteins in the db/db mice. 27757071 3 9 from adhesion 451:458 arg1 important 433:441 important 433:441 important 433:441 These glycosylated proteins are highly important in cell adhesion and cell-matrix processes but not much is known about how they change in DN or whether the distinct etiology of T1DM and T2DM could have an effect on their abundances. 27757071 1 10 theme type 174:177 arg1 T1DM 200:203 T1DM 200:203 T1DM 200:203 BACKGROUND Diabetic nephropathy (DN) is a late complication in both type 1 diabetes mellitus (T1DM) and T2DM. 27757071 1 10 theme type 174:177 arg1 mellitus 190:197 type 1 diabetes mellitus 174:197 type 1 diabetes mellitus (T1DM) 174:204 BACKGROUND Diabetic nephropathy (DN) is a late complication in both type 1 diabetes mellitus (T1DM) and T2DM. 27757071 1 11 theme diabetes 181:188 arg1 T1DM 200:203 T1DM 200:203 T1DM 200:203 BACKGROUND Diabetic nephropathy (DN) is a late complication in both type 1 diabetes mellitus (T1DM) and T2DM. 27757071 1 11 theme diabetes 181:188 arg1 mellitus 190:197 type 1 diabetes mellitus 174:197 type 1 diabetes mellitus (T1DM) 174:204 BACKGROUND Diabetic nephropathy (DN) is a late complication in both type 1 diabetes mellitus (T1DM) and T2DM. 27757071 9 12 theme coupled 1640:1646 arg1 receptor-116 1648:1659 G-protein coupled receptor-116 1630:1659 G-protein coupled receptor-116 1630:1659 It decreased the abundance of G-protein coupled receptor-116 and of tyrosine-protein phosphatase non-receptor type substrate-1 away from the level in the healthy control mice. 27757071 3 13 contain have 592:595 arg1 etiology 560:567 the distinct etiology 547:567 the distinct etiology of T1DM and T2DM 547:584 These glycosylated proteins are highly important in cell adhesion and cell-matrix processes but not much is known about how they change in DN or whether the distinct etiology of T1DM and T2DM could have an effect on their abundances. 27757071 3 13 contain have 592:595 arg2 effect 600:605 an effect 597:605 an effect 597:605 These glycosylated proteins are highly important in cell adhesion and cell-matrix processes but not much is known about how they change in DN or whether the distinct etiology of T1DM and T2DM could have an effect on their abundances. 27757071 1 14 theme BACKGROUND 106:115 arg1 complication 153:164 a late complication 146:164 a late complication in both type 1 diabetes mellitus (T1DM) and T2DM 146:213 BACKGROUND Diabetic nephropathy (DN) is a late complication in both type 1 diabetes mellitus (T1DM) and T2DM. 27757071 1 14 theme BACKGROUND 106:115 arg1 nephropathy 126:136 BACKGROUND Diabetic nephropathy 106:136 BACKGROUND Diabetic nephropathy (DN) 106:141 BACKGROUND Diabetic nephropathy (DN) is a late complication in both type 1 diabetes mellitus (T1DM) and T2DM. 27757071 10 15 theme DN 1918:1919 arg1 etiology 1906:1913 the etiology 1902:1913 the etiology of DN 1902:1919 CONCLUSIONS Our finding of differences in the N-glycosylation protein profiles in the db/db and STZ mouse models suggest that the etiology of DN could give rise to variations in the cell adhesion and cell-matrix composition in T1DM and T2DM. 27757071 4 16 gly N-glycosylated 655:668 arg1 proteome 677:684 the N-glycosylated kidney proteome 651:684 the N-glycosylated kidney proteome in db/db mice dosed with insulin or vehicle 651:728 METHOD We enriched for the N-glycosylated kidney proteome in db/db mice dosed with insulin or vehicle, in streptozotocin-induced (STZ) diabetic mice and healthy control mice dosed with vehicle. 27757071 10 17 dep CONCLUSIONS 1776:1786 arg1 finding 1792:1798 Our finding 1788:1798 CONCLUSIONS Our finding of differences in the N-glycosylation protein profiles in the db/db and STZ mouse models 1776:1887 CONCLUSIONS Our finding of differences in the N-glycosylation protein profiles in the db/db and STZ mouse models suggest that the etiology of DN could give rise to variations in the cell adhesion and cell-matrix composition in T1DM and T2DM. 27757071 9 18 theme tyrosine-protein 1668:1683 arg1 substrate-1 1715:1725 tyrosine-protein phosphatase non-receptor type substrate-1 1668:1725 tyrosine-protein phosphatase non-receptor type substrate-1 1668:1725 It decreased the abundance of G-protein coupled receptor-116 and of tyrosine-protein phosphatase non-receptor type substrate-1 away from the level in the healthy control mice. 27757071 12 19 theme control 2279:2285 arg1 mice 2287:2290 healthy control mice 2271:2290 healthy control mice 2271:2290 Furthermore, we observed insulin specific regulation of N-glycosylated proteins both in the direction of and away from the abundances in healthy control mice. 27757071 4 20 theme N-glycosylated 655:668 arg1 proteome 677:684 the N-glycosylated kidney proteome 651:684 the N-glycosylated kidney proteome in db/db mice dosed with insulin or vehicle 651:728 METHOD We enriched for the N-glycosylated kidney proteome in db/db mice dosed with insulin or vehicle, in streptozotocin-induced (STZ) diabetic mice and healthy control mice dosed with vehicle. 27757071 2 21 contain carry 363:367 arg1 majority 338:345 the majority 334:345 the majority of the proteins 334:361 Already at an early stage of DN morphological changes occur at the cell surface and in the extracellular matrix where the majority of the proteins carry N-linked glycosylations. 27757071 2 21 contain carry 363:367 arg2 glycosylations 378:391 N-linked glycosylations 369:391 N-linked glycosylations 369:391 Already at an early stage of DN morphological changes occur at the cell surface and in the extracellular matrix where the majority of the proteins carry N-linked glycosylations. 27757071 5 22 theme shotgun 866:872 arg1 spectrometry 879:890 label-free shotgun mass spectrometry 855:890 label-free shotgun mass spectrometry 855:890 Glycopeptides were analyzed with label-free shotgun mass spectrometry and differential protein abundances identified in both mouse models were compared using multivariate analyses. 27757071 9 23 theme non-receptor 1697:1708 arg1 substrate-1 1715:1725 tyrosine-protein phosphatase non-receptor type substrate-1 1668:1725 tyrosine-protein phosphatase non-receptor type substrate-1 1668:1725 It decreased the abundance of G-protein coupled receptor-116 and of tyrosine-protein phosphatase non-receptor type substrate-1 away from the level in the healthy control mice. 27757071 7 24 theme db/db 1322:1326 arg1 mice 1328:1331 the db/db mice 1318:1331 the db/db mice 1318:1331 However, distinct differences between the two mouse models were for example seen for integrin-β1, a protein expressed mainly in the glomeruli which abundance was increased in the STZ diabetic mice while decreased in the db/db mice and for the sodium/glucose cotransporter-1, mainly expressed in the proximal tubules which abundance was increased in the db/db mice but decreased in the STZ diabetic mice. 27757071 5 25 theme protein 909:915 arg1 abundances 917:926 differential protein abundances 896:926 differential protein abundances identified in both mouse models 896:958 Glycopeptides were analyzed with label-free shotgun mass spectrometry and differential protein abundances identified in both mouse models were compared using multivariate analyses. 27757071 3 26 theme T2DM 581:584 arg1 etiology 560:567 the distinct etiology 547:567 the distinct etiology of T1DM and T2DM 547:584 These glycosylated proteins are highly important in cell adhesion and cell-matrix processes but not much is known about how they change in DN or whether the distinct etiology of T1DM and T2DM could have an effect on their abundances. 27757071 11 27 gly N-glycosylated 2024:2037 arg1 clue 2070:2073 a clue 2068:2073 a clue to dissimilarities in T1DM and T2DM 2068:2109 Thus, N-glycosylated protein differences could be a clue to dissimilarities in T1DM and T2DM at later stages of DN. 27757071 11 27 gly N-glycosylated 2024:2037 arg1 differences 2047:2057 N-glycosylated protein differences 2024:2057 N-glycosylated protein differences 2024:2057 Thus, N-glycosylated protein differences could be a clue to dissimilarities in T1DM and T2DM at later stages of DN. 27757071 9 28 theme substrate-1 1715:1725 arg1 abundance 1617:1625 the abundance 1613:1625 the abundance of G-protein coupled receptor-116 and of tyrosine-protein phosphatase non-receptor type substrate-1 1613:1725 It decreased the abundance of G-protein coupled receptor-116 and of tyrosine-protein phosphatase non-receptor type substrate-1 away from the level in the healthy control mice. 27757071 10 29 dep adhesion 1963:1970 arg1 the 1954:1956 the 1954:1956 the 1954:1956 CONCLUSIONS Our finding of differences in the N-glycosylation protein profiles in the db/db and STZ mouse models suggest that the etiology of DN could give rise to variations in the cell adhesion and cell-matrix composition in T1DM and T2DM. 27757071 10 30 theme cell 1958:1961 arg1 adhesion 1963:1970 cell adhesion 1958:1970 cell adhesion 1958:1970 CONCLUSIONS Our finding of differences in the N-glycosylation protein profiles in the db/db and STZ mouse models suggest that the etiology of DN could give rise to variations in the cell adhesion and cell-matrix composition in T1DM and T2DM. 27757071 0 31 theme enrichment 25:34 arg1 analysis 36:43 N-glycosylation proteome enrichment analysis 0:43 N-glycosylation proteome enrichment analysis in kidney 0:53 N-glycosylation proteome enrichment analysis in kidney reveals differences between diabetic mouse models. 27757071 1 32 theme late 148:151 arg1 complication 153:164 a late complication 146:164 a late complication in both type 1 diabetes mellitus (T1DM) and T2DM 146:213 BACKGROUND Diabetic nephropathy (DN) is a late complication in both type 1 diabetes mellitus (T1DM) and T2DM. 27757071 1 32 theme late 148:151 arg1 nephropathy 126:136 BACKGROUND Diabetic nephropathy 106:136 BACKGROUND Diabetic nephropathy (DN) 106:141 BACKGROUND Diabetic nephropathy (DN) is a late complication in both type 1 diabetes mellitus (T1DM) and T2DM. 27757071 8 33 contain had 1514:1516 arg1 Insulin 1506:1512 Insulin 1506:1512 Insulin 1506:1512 Insulin had an effect on the level of both glomerular and tubular proteins in the db/db mice. 27757071 8 33 contain had 1514:1516 arg2 effect 1521:1526 an effect 1518:1526 an effect 1518:1526 Insulin had an effect on the level of both glomerular and tubular proteins in the db/db mice. 27757071 0 34 theme mouse 92:96 arg1 models 98:103 diabetic mouse models 83:103 diabetic mouse models 83:103 N-glycosylation proteome enrichment analysis in kidney reveals differences between diabetic mouse models. 27757071 1 35 from complication 153:164 arg1 T1DM 200:203 T1DM 200:203 T1DM 200:203 BACKGROUND Diabetic nephropathy (DN) is a late complication in both type 1 diabetes mellitus (T1DM) and T2DM. 27757071 1 35 from complication 153:164 arg1 T2DM 210:213 T2DM 210:213 T2DM 210:213 BACKGROUND Diabetic nephropathy (DN) is a late complication in both type 1 diabetes mellitus (T1DM) and T2DM. 27757071 1 35 from complication 153:164 arg1 mellitus 190:197 type 1 diabetes mellitus 174:197 type 1 diabetes mellitus (T1DM) 174:204 BACKGROUND Diabetic nephropathy (DN) is a late complication in both type 1 diabetes mellitus (T1DM) and T2DM. 27757071 2 36 theme early 230:234 arg1 stage 236:240 an early stage 227:240 an early stage of DN morphological changes 227:268 Already at an early stage of DN morphological changes occur at the cell surface and in the extracellular matrix where the majority of the proteins carry N-linked glycosylations. 27757071 12 37 theme specific 2167:2174 arg1 regulation 2176:2185 insulin specific regulation 2159:2185 insulin specific regulation of N-glycosylated proteins 2159:2212 Furthermore, we observed insulin specific regulation of N-glycosylated proteins both in the direction of and away from the abundances in healthy control mice. 27757071 12 38 theme N-glycosylated 2190:2203 arg1 proteins 2205:2212 N-glycosylated proteins 2190:2212 N-glycosylated proteins 2190:2212 Furthermore, we observed insulin specific regulation of N-glycosylated proteins both in the direction of and away from the abundances in healthy control mice. 27757071 2 39 theme proteins 354:361 arg1 majority 338:345 the majority 334:345 the majority of the proteins 334:361 Already at an early stage of DN morphological changes occur at the cell surface and in the extracellular matrix where the majority of the proteins carry N-linked glycosylations. 27757071 4 40 dep METHOD 628:633 arg1 enriched 638:645 enriched 638:645 enriched 638:645 METHOD We enriched for the N-glycosylated kidney proteome in db/db mice dosed with insulin or vehicle, in streptozotocin-induced (STZ) diabetic mice and healthy control mice dosed with vehicle. 27757071 9 41 theme control 1762:1768 arg1 mice 1770:1773 the healthy control mice 1750:1773 the healthy control mice 1750:1773 It decreased the abundance of G-protein coupled receptor-116 and of tyrosine-protein phosphatase non-receptor type substrate-1 away from the level in the healthy control mice. 27757071 4 42 theme db/db 689:693 arg1 mice 695:698 db/db mice 689:698 db/db mice dosed with insulin or vehicle 689:728 METHOD We enriched for the N-glycosylated kidney proteome in db/db mice dosed with insulin or vehicle, in streptozotocin-induced (STZ) diabetic mice and healthy control mice dosed with vehicle. 27757071 0 43 theme N-glycosylation 0:14 arg1 analysis 36:43 N-glycosylation proteome enrichment analysis 0:43 N-glycosylation proteome enrichment analysis in kidney 0:53 N-glycosylation proteome enrichment analysis in kidney reveals differences between diabetic mouse models. 27757071 10 44 from variations 1940:1949 arg1 adhesion 1963:1970 cell adhesion 1958:1970 cell adhesion 1958:1970 CONCLUSIONS Our finding of differences in the N-glycosylation protein profiles in the db/db and STZ mouse models suggest that the etiology of DN could give rise to variations in the cell adhesion and cell-matrix composition in T1DM and T2DM. 27757071 10 44 from variations 1940:1949 arg1 composition 1988:1998 cell-matrix composition 1976:1998 cell-matrix composition 1976:1998 CONCLUSIONS Our finding of differences in the N-glycosylation protein profiles in the db/db and STZ mouse models suggest that the etiology of DN could give rise to variations in the cell adhesion and cell-matrix composition in T1DM and T2DM. 27757071 5 45 theme differential 896:907 arg1 abundances 917:926 differential protein abundances 896:926 differential protein abundances identified in both mouse models 896:958 Glycopeptides were analyzed with label-free shotgun mass spectrometry and differential protein abundances identified in both mouse models were compared using multivariate analyses. 27757071 10 46 from finding 1792:1798 arg1 profiles 1846:1853 the N-glycosylation protein profiles 1818:1853 the N-glycosylation protein profiles in the db/db and STZ mouse models 1818:1887 CONCLUSIONS Our finding of differences in the N-glycosylation protein profiles in the db/db and STZ mouse models suggest that the etiology of DN could give rise to variations in the cell adhesion and cell-matrix composition in T1DM and T2DM. 27757071 6 47 theme N-glycosylated 1031:1044 arg1 proteins 1046:1053 the N-glycosylated proteins 1027:1053 the N-glycosylated proteins 1027:1053 RESULTS The majority of the N-glycosylated proteins were similarly regulated in both mouse models. 27757071 7 48 theme mouse 1148:1152 arg1 models 1154:1159 the two mouse models 1140:1159 the two mouse models 1140:1159 However, distinct differences between the two mouse models were for example seen for integrin-β1, a protein expressed mainly in the glomeruli which abundance was increased in the STZ diabetic mice while decreased in the db/db mice and for the sodium/glucose cotransporter-1, mainly expressed in the proximal tubules which abundance was increased in the db/db mice but decreased in the STZ diabetic mice. 27757071 10 49 from differences 1803:1813 arg1 profiles 1846:1853 the N-glycosylation protein profiles 1818:1853 the N-glycosylation protein profiles in the db/db and STZ mouse models 1818:1887 CONCLUSIONS Our finding of differences in the N-glycosylation protein profiles in the db/db and STZ mouse models suggest that the etiology of DN could give rise to variations in the cell adhesion and cell-matrix composition in T1DM and T2DM. 27757071 7 50 theme STZ 1281:1283 arg1 mice 1294:1297 the STZ diabetic mice 1277:1297 the STZ diabetic mice 1277:1297 However, distinct differences between the two mouse models were for example seen for integrin-β1, a protein expressed mainly in the glomeruli which abundance was increased in the STZ diabetic mice while decreased in the db/db mice and for the sodium/glucose cotransporter-1, mainly expressed in the proximal tubules which abundance was increased in the db/db mice but decreased in the STZ diabetic mice. 27757071 11 51 theme DN 2130:2131 arg1 stages 2120:2125 later stages 2114:2125 later stages of DN 2114:2131 Thus, N-glycosylated protein differences could be a clue to dissimilarities in T1DM and T2DM at later stages of DN. 27757071 10 52 theme N-glycosylation 1822:1836 arg1 profiles 1846:1853 the N-glycosylation protein profiles 1818:1853 the N-glycosylation protein profiles in the db/db and STZ mouse models 1818:1887 CONCLUSIONS Our finding of differences in the N-glycosylation protein profiles in the db/db and STZ mouse models suggest that the etiology of DN could give rise to variations in the cell adhesion and cell-matrix composition in T1DM and T2DM. 27757071 2 53 theme N-linked 369:376 arg1 glycosylations 378:391 N-linked glycosylations 369:391 N-linked glycosylations 369:391 Already at an early stage of DN morphological changes occur at the cell surface and in the extracellular matrix where the majority of the proteins carry N-linked glycosylations. 27757071 10 54 from adhesion 1963:1970 arg1 T2DM 2012:2015 T2DM 2012:2015 T2DM 2012:2015 CONCLUSIONS Our finding of differences in the N-glycosylation protein profiles in the db/db and STZ mouse models suggest that the etiology of DN could give rise to variations in the cell adhesion and cell-matrix composition in T1DM and T2DM. 27757071 10 54 from adhesion 1963:1970 arg1 T1DM 2003:2006 T1DM 2003:2006 T1DM 2003:2006 CONCLUSIONS Our finding of differences in the N-glycosylation protein profiles in the db/db and STZ mouse models suggest that the etiology of DN could give rise to variations in the cell adhesion and cell-matrix composition in T1DM and T2DM. 27757071 9 55 from level 1741:1745 arg1 mice 1770:1773 the healthy control mice 1750:1773 the healthy control mice 1750:1773 It decreased the abundance of G-protein coupled receptor-116 and of tyrosine-protein phosphatase non-receptor type substrate-1 away from the level in the healthy control mice. 27757071 3 56 from important 433:441 arg1 adhesion 451:458 cell adhesion 446:458 cell adhesion 446:458 These glycosylated proteins are highly important in cell adhesion and cell-matrix processes but not much is known about how they change in DN or whether the distinct etiology of T1DM and T2DM could have an effect on their abundances. 27757071 3 57 theme cell-matrix 464:474 arg1 proteins 413:420 These glycosylated proteins 394:420 These glycosylated proteins 394:420 These glycosylated proteins are highly important in cell adhesion and cell-matrix processes but not much is known about how they change in DN or whether the distinct etiology of T1DM and T2DM could have an effect on their abundances. 27757071 3 57 theme cell-matrix 464:474 arg1 processes 476:484 highly important in cell adhesion and cell-matrix processes 426:484 highly important in cell adhesion and cell-matrix processes 426:484 These glycosylated proteins are highly important in cell adhesion and cell-matrix processes but not much is known about how they change in DN or whether the distinct etiology of T1DM and T2DM could have an effect on their abundances. 27757071 7 58 theme STZ 1487:1489 arg1 mice 1500:1503 the STZ diabetic mice 1483:1503 the STZ diabetic mice 1483:1503 However, distinct differences between the two mouse models were for example seen for integrin-β1, a protein expressed mainly in the glomeruli which abundance was increased in the STZ diabetic mice while decreased in the db/db mice and for the sodium/glucose cotransporter-1, mainly expressed in the proximal tubules which abundance was increased in the db/db mice but decreased in the STZ diabetic mice. 27757071 3 59 theme T1DM 572:575 arg1 etiology 560:567 the distinct etiology 547:567 the distinct etiology of T1DM and T2DM 547:584 These glycosylated proteins are highly important in cell adhesion and cell-matrix processes but not much is known about how they change in DN or whether the distinct etiology of T1DM and T2DM could have an effect on their abundances. 27757071 6 60 gly N-glycosylated 1031:1044 arg1 proteins 1046:1053 the N-glycosylated proteins 1027:1053 the N-glycosylated proteins 1027:1053 RESULTS The majority of the N-glycosylated proteins were similarly regulated in both mouse models. 27757071 3 61 gly glycosylated 400:411 arg1 proteins 413:420 These glycosylated proteins 394:420 These glycosylated proteins 394:420 These glycosylated proteins are highly important in cell adhesion and cell-matrix processes but not much is known about how they change in DN or whether the distinct etiology of T1DM and T2DM could have an effect on their abundances. 27757071 3 61 gly glycosylated 400:411 arg1 processes 476:484 highly important in cell adhesion and cell-matrix processes 426:484 highly important in cell adhesion and cell-matrix processes 426:484 These glycosylated proteins are highly important in cell adhesion and cell-matrix processes but not much is known about how they change in DN or whether the distinct etiology of T1DM and T2DM could have an effect on their abundances. 27757071 7 62 theme db/db 1455:1459 arg1 mice 1461:1464 the db/db mice 1451:1464 the db/db mice 1451:1464 However, distinct differences between the two mouse models were for example seen for integrin-β1, a protein expressed mainly in the glomeruli which abundance was increased in the STZ diabetic mice while decreased in the db/db mice and for the sodium/glucose cotransporter-1, mainly expressed in the proximal tubules which abundance was increased in the db/db mice but decreased in the STZ diabetic mice. 27757071 10 63 theme mouse 1876:1880 arg1 models 1882:1887 the db/db and STZ mouse models 1858:1887 models 1882:1887 CONCLUSIONS Our finding of differences in the N-glycosylation protein profiles in the db/db and STZ mouse models suggest that the etiology of DN could give rise to variations in the cell adhesion and cell-matrix composition in T1DM and T2DM. 27757071 8 64 theme proteins 1572:1579 arg1 level 1535:1539 the level 1531:1539 the level of both glomerular and tubular proteins in the db/db mice 1531:1597 Insulin had an effect on the level of both glomerular and tubular proteins in the db/db mice. 27757071 2 65 theme changes 262:268 arg1 stage 236:240 an early stage 227:240 an early stage of DN morphological changes 227:268 Already at an early stage of DN morphological changes occur at the cell surface and in the extracellular matrix where the majority of the proteins carry N-linked glycosylations. 27757071 10 66 from profiles 1846:1853 arg1 finding 1792:1798 Our finding 1788:1798 CONCLUSIONS Our finding of differences in the N-glycosylation protein profiles in the db/db and STZ mouse models 1776:1887 CONCLUSIONS Our finding of differences in the N-glycosylation protein profiles in the db/db and STZ mouse models suggest that the etiology of DN could give rise to variations in the cell adhesion and cell-matrix composition in T1DM and T2DM. 27757071 10 66 from profiles 1846:1853 arg1 models 1882:1887 the db/db and STZ mouse models 1858:1887 models 1882:1887 CONCLUSIONS Our finding of differences in the N-glycosylation protein profiles in the db/db and STZ mouse models suggest that the etiology of DN could give rise to variations in the cell adhesion and cell-matrix composition in T1DM and T2DM. 27757071 10 66 from profiles 1846:1853 arg1 db/db 1862:1866 the db/db and STZ mouse models 1858:1887 db/db 1862:1866 CONCLUSIONS Our finding of differences in the N-glycosylation protein profiles in the db/db and STZ mouse models suggest that the etiology of DN could give rise to variations in the cell adhesion and cell-matrix composition in T1DM and T2DM. 27757071 2 67 theme DN 245:246 arg1 changes 262:268 DN morphological changes 245:268 DN morphological changes 245:268 Already at an early stage of DN morphological changes occur at the cell surface and in the extracellular matrix where the majority of the proteins carry N-linked glycosylations. 27757071 2 68 theme cell 283:286 arg1 surface 288:294 the cell surface 279:294 the cell surface 279:294 Already at an early stage of DN morphological changes occur at the cell surface and in the extracellular matrix where the majority of the proteins carry N-linked glycosylations. 27757071 4 69 theme control 789:795 arg1 mice 797:800 healthy control mice 781:800 healthy control mice dosed with vehicle 781:819 METHOD We enriched for the N-glycosylated kidney proteome in db/db mice dosed with insulin or vehicle, in streptozotocin-induced (STZ) diabetic mice and healthy control mice dosed with vehicle. 27757071 11 70 from dissimilarities 2078:2092 arg1 T2DM 2106:2109 T2DM 2106:2109 T2DM 2106:2109 Thus, N-glycosylated protein differences could be a clue to dissimilarities in T1DM and T2DM at later stages of DN. 27757071 11 70 from dissimilarities 2078:2092 arg1 T1DM 2097:2100 T1DM 2097:2100 T1DM 2097:2100 Thus, N-glycosylated protein differences could be a clue to dissimilarities in T1DM and T2DM at later stages of DN. 27757071 9 71 theme receptor-116 1648:1659 arg1 abundance 1617:1625 the abundance 1613:1625 the abundance of G-protein coupled receptor-116 and of tyrosine-protein phosphatase non-receptor type substrate-1 1613:1725 It decreased the abundance of G-protein coupled receptor-116 and of tyrosine-protein phosphatase non-receptor type substrate-1 away from the level in the healthy control mice. 27757071 12 72 theme healthy 2271:2277 arg1 mice 2287:2290 healthy control mice 2271:2290 healthy control mice 2271:2290 Furthermore, we observed insulin specific regulation of N-glycosylated proteins both in the direction of and away from the abundances in healthy control mice. 27757071 9 73 theme G-protein 1630:1638 arg1 receptor-116 1648:1659 G-protein coupled receptor-116 1630:1659 G-protein coupled receptor-116 1630:1659 It decreased the abundance of G-protein coupled receptor-116 and of tyrosine-protein phosphatase non-receptor type substrate-1 away from the level in the healthy control mice. 27757071 3 74 theme distinct 551:558 arg1 etiology 560:567 the distinct etiology 547:567 the distinct etiology of T1DM and T2DM 547:584 These glycosylated proteins are highly important in cell adhesion and cell-matrix processes but not much is known about how they change in DN or whether the distinct etiology of T1DM and T2DM could have an effect on their abundances. 27757071 7 75 theme sodium/glucose 1345:1358 arg1 cotransporter-1 1360:1374 the sodium/glucose cotransporter-1 1341:1374 the sodium/glucose cotransporter-1 1341:1374 However, distinct differences between the two mouse models were for example seen for integrin-β1, a protein expressed mainly in the glomeruli which abundance was increased in the STZ diabetic mice while decreased in the db/db mice and for the sodium/glucose cotransporter-1, mainly expressed in the proximal tubules which abundance was increased in the db/db mice but decreased in the STZ diabetic mice. 27757071 5 76 theme label-free 855:864 arg1 spectrometry 879:890 label-free shotgun mass spectrometry 855:890 label-free shotgun mass spectrometry 855:890 Glycopeptides were analyzed with label-free shotgun mass spectrometry and differential protein abundances identified in both mouse models were compared using multivariate analyses. 27757071 9 77 theme phosphatase 1685:1695 arg1 substrate-1 1715:1725 tyrosine-protein phosphatase non-receptor type substrate-1 1668:1725 tyrosine-protein phosphatase non-receptor type substrate-1 1668:1725 It decreased the abundance of G-protein coupled receptor-116 and of tyrosine-protein phosphatase non-receptor type substrate-1 away from the level in the healthy control mice. 27757071 10 78 theme differences 1803:1813 arg1 finding 1792:1798 Our finding 1788:1798 CONCLUSIONS Our finding of differences in the N-glycosylation protein profiles in the db/db and STZ mouse models 1776:1887 CONCLUSIONS Our finding of differences in the N-glycosylation protein profiles in the db/db and STZ mouse models suggest that the etiology of DN could give rise to variations in the cell adhesion and cell-matrix composition in T1DM and T2DM. 27757071 5 79 theme mass 874:877 arg1 spectrometry 879:890 label-free shotgun mass spectrometry 855:890 label-free shotgun mass spectrometry 855:890 Glycopeptides were analyzed with label-free shotgun mass spectrometry and differential protein abundances identified in both mouse models were compared using multivariate analyses. 27757071 9 80 theme type 1710:1713 arg1 substrate-1 1715:1725 tyrosine-protein phosphatase non-receptor type substrate-1 1668:1725 tyrosine-protein phosphatase non-receptor type substrate-1 1668:1725 It decreased the abundance of G-protein coupled receptor-116 and of tyrosine-protein phosphatase non-receptor type substrate-1 away from the level in the healthy control mice. 27757071 4 81 theme kidney 670:675 arg1 proteome 677:684 the N-glycosylated kidney proteome 651:684 the N-glycosylated kidney proteome in db/db mice dosed with insulin or vehicle 651:728 METHOD We enriched for the N-glycosylated kidney proteome in db/db mice dosed with insulin or vehicle, in streptozotocin-induced (STZ) diabetic mice and healthy control mice dosed with vehicle. 27757071 0 82 theme diabetic 83:90 arg1 models 98:103 diabetic mouse models 83:103 diabetic mouse models 83:103 N-glycosylation proteome enrichment analysis in kidney reveals differences between diabetic mouse models. 27757071 12 83 gly N-glycosylated 2190:2203 arg1 proteins 2205:2212 N-glycosylated proteins 2190:2212 N-glycosylated proteins 2190:2212 Furthermore, we observed insulin specific regulation of N-glycosylated proteins both in the direction of and away from the abundances in healthy control mice. 27757071 0 84 from analysis 36:43 arg1 kidney 48:53 kidney 48:53 kidney 48:53 N-glycosylation proteome enrichment analysis in kidney reveals differences between diabetic mouse models. 27757071 1 85 dep nephropathy 126:136 arg1 DN 139:140 DN 139:140 DN 139:140 BACKGROUND Diabetic nephropathy (DN) is a late complication in both type 1 diabetes mellitus (T1DM) and T2DM. 27757071 12 86 theme proteins 2205:2212 arg1 regulation 2176:2185 insulin specific regulation 2159:2185 insulin specific regulation of N-glycosylated proteins 2159:2212 Furthermore, we observed insulin specific regulation of N-glycosylated proteins both in the direction of and away from the abundances in healthy control mice. 27757071 12 87 theme insulin 2159:2165 arg1 regulation 2176:2185 insulin specific regulation 2159:2185 insulin specific regulation of N-glycosylated proteins 2159:2212 Furthermore, we observed insulin specific regulation of N-glycosylated proteins both in the direction of and away from the abundances in healthy control mice. 27757071 10 88 theme cell-matrix 1976:1986 arg1 composition 1988:1998 cell-matrix composition 1976:1998 cell-matrix composition 1976:1998 CONCLUSIONS Our finding of differences in the N-glycosylation protein profiles in the db/db and STZ mouse models suggest that the etiology of DN could give rise to variations in the cell adhesion and cell-matrix composition in T1DM and T2DM. 27757071 9 89 theme healthy 1754:1760 arg1 mice 1770:1773 the healthy control mice 1750:1773 the healthy control mice 1750:1773 It decreased the abundance of G-protein coupled receptor-116 and of tyrosine-protein phosphatase non-receptor type substrate-1 away from the level in the healthy control mice. 27757071 6 90 dep RESULTS 1003:1009 arg1 majority 1015:1022 The majority 1011:1022 RESULTS The majority of the N-glycosylated proteins 1003:1053 RESULTS The majority of the N-glycosylated proteins were similarly regulated in both mouse models. 27757071 0 91 theme proteome 16:23 arg1 analysis 36:43 N-glycosylation proteome enrichment analysis 0:43 N-glycosylation proteome enrichment analysis in kidney 0:53 N-glycosylation proteome enrichment analysis in kidney reveals differences between diabetic mouse models. 27757071 11 92 theme N-glycosylated 2024:2037 arg1 clue 2070:2073 a clue 2068:2073 a clue to dissimilarities in T1DM and T2DM 2068:2109 Thus, N-glycosylated protein differences could be a clue to dissimilarities in T1DM and T2DM at later stages of DN. 27757071 11 92 theme N-glycosylated 2024:2037 arg1 differences 2047:2057 N-glycosylated protein differences 2024:2057 N-glycosylated protein differences 2024:2057 Thus, N-glycosylated protein differences could be a clue to dissimilarities in T1DM and T2DM at later stages of DN. 27757071 7 93 theme diabetic 1285:1292 arg1 mice 1294:1297 the STZ diabetic mice 1277:1297 the STZ diabetic mice 1277:1297 However, distinct differences between the two mouse models were for example seen for integrin-β1, a protein expressed mainly in the glomeruli which abundance was increased in the STZ diabetic mice while decreased in the db/db mice and for the sodium/glucose cotransporter-1, mainly expressed in the proximal tubules which abundance was increased in the db/db mice but decreased in the STZ diabetic mice. 27757071 11 94 theme later 2114:2118 arg1 stages 2120:2125 later stages 2114:2125 later stages of DN 2114:2131 Thus, N-glycosylated protein differences could be a clue to dissimilarities in T1DM and T2DM at later stages of DN. 27757071 3 95 theme glycosylated 400:411 arg1 proteins 413:420 These glycosylated proteins 394:420 These glycosylated proteins 394:420 These glycosylated proteins are highly important in cell adhesion and cell-matrix processes but not much is known about how they change in DN or whether the distinct etiology of T1DM and T2DM could have an effect on their abundances. 27757071 3 95 theme glycosylated 400:411 arg1 processes 476:484 highly important in cell adhesion and cell-matrix processes 426:484 highly important in cell adhesion and cell-matrix processes 426:484 These glycosylated proteins are highly important in cell adhesion and cell-matrix processes but not much is known about how they change in DN or whether the distinct etiology of T1DM and T2DM could have an effect on their abundances. 27757071 1 96 theme Diabetic 117:124 arg1 complication 153:164 a late complication 146:164 a late complication in both type 1 diabetes mellitus (T1DM) and T2DM 146:213 BACKGROUND Diabetic nephropathy (DN) is a late complication in both type 1 diabetes mellitus (T1DM) and T2DM. 27757071 1 96 theme Diabetic 117:124 arg1 nephropathy 126:136 BACKGROUND Diabetic nephropathy 106:136 BACKGROUND Diabetic nephropathy (DN) 106:141 BACKGROUND Diabetic nephropathy (DN) is a late complication in both type 1 diabetes mellitus (T1DM) and T2DM. 27757071 10 97 theme protein 1838:1844 arg1 profiles 1846:1853 the N-glycosylation protein profiles 1818:1853 the N-glycosylation protein profiles in the db/db and STZ mouse models 1818:1887 CONCLUSIONS Our finding of differences in the N-glycosylation protein profiles in the db/db and STZ mouse models suggest that the etiology of DN could give rise to variations in the cell adhesion and cell-matrix composition in T1DM and T2DM. 27757071 3 98 theme cell 446:449 arg1 adhesion 451:458 cell adhesion 446:458 cell adhesion 446:458 These glycosylated proteins are highly important in cell adhesion and cell-matrix processes but not much is known about how they change in DN or whether the distinct etiology of T1DM and T2DM could have an effect on their abundances. 27757071 12 99 from abundances 2257:2266 arg1 mice 2287:2290 healthy control mice 2271:2290 healthy control mice 2271:2290 Furthermore, we observed insulin specific regulation of N-glycosylated proteins both in the direction of and away from the abundances in healthy control mice. 27757071 5 100 theme multivariate 980:991 arg1 analyses 993:1000 multivariate analyses 980:1000 multivariate analyses 980:1000 Glycopeptides were analyzed with label-free shotgun mass spectrometry and differential protein abundances identified in both mouse models were compared using multivariate analyses. 27757071 4 101 theme STZ 758:760 arg1 mice 772:775 streptozotocin-induced (STZ) diabetic mice 734:775 streptozotocin-induced (STZ) diabetic mice 734:775 METHOD We enriched for the N-glycosylated kidney proteome in db/db mice dosed with insulin or vehicle, in streptozotocin-induced (STZ) diabetic mice and healthy control mice dosed with vehicle. 27757071 3 102 theme important 433:441 arg1 proteins 413:420 These glycosylated proteins 394:420 These glycosylated proteins 394:420 These glycosylated proteins are highly important in cell adhesion and cell-matrix processes but not much is known about how they change in DN or whether the distinct etiology of T1DM and T2DM could have an effect on their abundances. 27757071 3 102 theme important 433:441 arg1 processes 476:484 highly important in cell adhesion and cell-matrix processes 426:484 highly important in cell adhesion and cell-matrix processes 426:484 These glycosylated proteins are highly important in cell adhesion and cell-matrix processes but not much is known about how they change in DN or whether the distinct etiology of T1DM and T2DM could have an effect on their abundances. 27757071 7 103 theme distinct 1111:1118 arg1 differences 1120:1130 distinct differences 1111:1130 distinct differences between the two mouse models 1111:1159 However, distinct differences between the two mouse models were for example seen for integrin-β1, a protein expressed mainly in the glomeruli which abundance was increased in the STZ diabetic mice while decreased in the db/db mice and for the sodium/glucose cotransporter-1, mainly expressed in the proximal tubules which abundance was increased in the db/db mice but decreased in the STZ diabetic mice. 27757071 10 104 from composition 1988:1998 arg1 T2DM 2012:2015 T2DM 2012:2015 T2DM 2012:2015 CONCLUSIONS Our finding of differences in the N-glycosylation protein profiles in the db/db and STZ mouse models suggest that the etiology of DN could give rise to variations in the cell adhesion and cell-matrix composition in T1DM and T2DM. 27757071 10 104 from composition 1988:1998 arg1 T1DM 2003:2006 T1DM 2003:2006 T1DM 2003:2006 CONCLUSIONS Our finding of differences in the N-glycosylation protein profiles in the db/db and STZ mouse models suggest that the etiology of DN could give rise to variations in the cell adhesion and cell-matrix composition in T1DM and T2DM. 27757071 7 105 theme diabetic 1491:1498 arg1 mice 1500:1503 the STZ diabetic mice 1483:1503 the STZ diabetic mice 1483:1503 However, distinct differences between the two mouse models were for example seen for integrin-β1, a protein expressed mainly in the glomeruli which abundance was increased in the STZ diabetic mice while decreased in the db/db mice and for the sodium/glucose cotransporter-1, mainly expressed in the proximal tubules which abundance was increased in the db/db mice but decreased in the STZ diabetic mice. 27757071 2 106 link N-linked 369:376 arg1 glycosylations 378:391 N-linked glycosylations 369:391 N-linked glycosylations 369:391 Already at an early stage of DN morphological changes occur at the cell surface and in the extracellular matrix where the majority of the proteins carry N-linked glycosylations. 27757071 4 107 theme diabetic 763:770 arg1 mice 772:775 streptozotocin-induced (STZ) diabetic mice 734:775 streptozotocin-induced (STZ) diabetic mice 734:775 METHOD We enriched for the N-glycosylated kidney proteome in db/db mice dosed with insulin or vehicle, in streptozotocin-induced (STZ) diabetic mice and healthy control mice dosed with vehicle. 27757071 4 108 from proteome 677:684 arg1 mice 695:698 db/db mice 689:698 db/db mice dosed with insulin or vehicle 689:728 METHOD We enriched for the N-glycosylated kidney proteome in db/db mice dosed with insulin or vehicle, in streptozotocin-induced (STZ) diabetic mice and healthy control mice dosed with vehicle. 27757071 8 109 theme glomerular 1549:1558 arg1 proteins 1572:1579 both glomerular and tubular proteins 1544:1579 both glomerular and tubular proteins 1544:1579 Insulin had an effect on the level of both glomerular and tubular proteins in the db/db mice. 27757071 5 110 theme mouse 947:951 arg1 models 953:958 both mouse models 942:958 both mouse models 942:958 Glycopeptides were analyzed with label-free shotgun mass spectrometry and differential protein abundances identified in both mouse models were compared using multivariate analyses. 27757071 6 111 theme mouse 1088:1092 arg1 models 1094:1099 both mouse models 1083:1099 both mouse models 1083:1099 RESULTS The majority of the N-glycosylated proteins were similarly regulated in both mouse models. 27757071 8 112 theme tubular 1564:1570 arg1 proteins 1572:1579 both glomerular and tubular proteins 1544:1579 both glomerular and tubular proteins 1544:1579 Insulin had an effect on the level of both glomerular and tubular proteins in the db/db mice. 27757071 11 113 from stages 2120:2125 arg1 clue 2070:2073 a clue 2068:2073 a clue to dissimilarities in T1DM and T2DM 2068:2109 Thus, N-glycosylated protein differences could be a clue to dissimilarities in T1DM and T2DM at later stages of DN. 27757071 11 113 from stages 2120:2125 arg1 differences 2047:2057 N-glycosylated protein differences 2024:2057 N-glycosylated protein differences 2024:2057 Thus, N-glycosylated protein differences could be a clue to dissimilarities in T1DM and T2DM at later stages of DN. 27757071 4 114 theme streptozotocin-induced 734:755 arg1 mice 772:775 streptozotocin-induced (STZ) diabetic mice 734:775 streptozotocin-induced (STZ) diabetic mice 734:775 METHOD We enriched for the N-glycosylated kidney proteome in db/db mice dosed with insulin or vehicle, in streptozotocin-induced (STZ) diabetic mice and healthy control mice dosed with vehicle. 24471554 11 0 theme other 1720:1724 arg1 species 1726:1732 other species 1720:1732 other species 1720:1732 Changes in glycosylation pattern have been related to pathological pregnancies in other species. 24471554 12 1 theme reproductive 1878:1889 arg1 events 1891:1896 both normal and pathological reproductive events 1849:1896 both normal and pathological reproductive events 1849:1896 Hence, the knowledge about glycosylation profile of the normal cat placenta may lead to a better understanding of both normal and pathological reproductive events. 24471554 2 2 theme ± 383:383 arg1 days 387:390 45 ± 5 days 380:390 45 ± 5 days of gestation 380:403 Samples from 12 normal pregnant female cats, after 45 ± 5 days of gestation, were obtained removing the uterine horns by hysterectomy. 24471554 7 3 theme glycans 1001:1007 arg1 population 987:996 a broad population 979:996 a broad population of glycans 979:1007 Trophoblast expressed a broad population of glycans, highly exposing terminal N-acetyl glucosamine residues and non-sialylated galactose and N-acetyl galactosamine oligomers. 24471554 1 4 theme decidual 276:283 arg1 cells 285:289 decidual cells 276:289 decidual cells 276:289 The aim of this study was to characterize cytoskeletal intermediate filament proteins and glycoconjugates of syncytiotrophoblast, cytotrophoblast and decidual cells of feline endotheliochorial placenta. 24471554 0 5 theme decidual 87:94 arg1 cells 96:100 trophoblast and decidual cells 71:100 cells 96:100 Intermediate filament proteins expression and carbohydrate moieties in trophoblast and decidual cells of mature cat placenta. 24471554 2 6 from cats 368:371 arg1 Samples 329:335 Samples 329:335 Samples from 12 normal pregnant female cats 329:371 Samples from 12 normal pregnant female cats, after 45 ± 5 days of gestation, were obtained removing the uterine horns by hysterectomy. 24471554 7 7 theme broad 981:985 arg1 population 987:996 a broad population 979:996 a broad population of glycans 979:1007 Trophoblast expressed a broad population of glycans, highly exposing terminal N-acetyl glucosamine residues and non-sialylated galactose and N-acetyl galactosamine oligomers. 24471554 1 8 theme cells 285:289 arg1 glycoconjugates 216:230 glycoconjugates 216:230 glycoconjugates of syncytiotrophoblast, cytotrophoblast and decidual cells of feline endotheliochorial placenta 216:326 The aim of this study was to characterize cytoskeletal intermediate filament proteins and glycoconjugates of syncytiotrophoblast, cytotrophoblast and decidual cells of feline endotheliochorial placenta. 24471554 1 8 theme cells 285:289 arg1 proteins 203:210 cytoskeletal intermediate filament proteins 168:210 cytoskeletal intermediate filament proteins 168:210 The aim of this study was to characterize cytoskeletal intermediate filament proteins and glycoconjugates of syncytiotrophoblast, cytotrophoblast and decidual cells of feline endotheliochorial placenta. 24471554 0 9 theme mature 105:110 arg1 placenta 116:123 mature cat placenta 105:123 mature cat placenta 105:123 Intermediate filament proteins expression and carbohydrate moieties in trophoblast and decidual cells of mature cat placenta. 24471554 10 10 theme properties 1531:1540 arg1 properties 1531:1540 their final properties 1519:1540 their final properties 1519:1540 Glycosylation of proteins determines many of their final properties, thus becoming essential for the embryo-maternal dialogue during implantation and placentation. 24471554 10 10 theme properties 1531:1540 arg1 many 1511:1514 many 1511:1514 many 1511:1514 Glycosylation of proteins determines many of their final properties, thus becoming essential for the embryo-maternal dialogue during implantation and placentation. 24471554 7 11 theme N-acetyl 1098:1105 arg1 oligomers 1121:1129 non-sialylated galactose and N-acetyl galactosamine oligomers 1069:1129 non-sialylated galactose and N-acetyl galactosamine oligomers 1069:1129 Trophoblast expressed a broad population of glycans, highly exposing terminal N-acetyl glucosamine residues and non-sialylated galactose and N-acetyl galactosamine oligomers. 24471554 3 12 theme antidesmin 581:590 arg1 antibodies 592:601 antidesmin antibodies 581:601 antidesmin antibodies 581:601 Sections were processed for routine observation and for immunohistochemistry using anticytokeratin, antivimentin and antidesmin antibodies. 24471554 12 13 theme pathological 1865:1876 arg1 events 1891:1896 both normal and pathological reproductive events 1849:1896 both normal and pathological reproductive events 1849:1896 Hence, the knowledge about glycosylation profile of the normal cat placenta may lead to a better understanding of both normal and pathological reproductive events. 24471554 7 14 theme non-sialylated 1069:1082 arg1 oligomers 1121:1129 non-sialylated galactose and N-acetyl galactosamine oligomers 1069:1129 non-sialylated galactose and N-acetyl galactosamine oligomers 1069:1129 Trophoblast expressed a broad population of glycans, highly exposing terminal N-acetyl glucosamine residues and non-sialylated galactose and N-acetyl galactosamine oligomers. 24471554 1 15 theme feline 294:299 arg1 placenta 319:326 feline endotheliochorial placenta 294:326 feline endotheliochorial placenta 294:326 The aim of this study was to characterize cytoskeletal intermediate filament proteins and glycoconjugates of syncytiotrophoblast, cytotrophoblast and decidual cells of feline endotheliochorial placenta. 24471554 0 16 theme placenta 116:123 arg1 expression 31:40 expression 31:40 expression 31:40 Intermediate filament proteins expression and carbohydrate moieties in trophoblast and decidual cells of mature cat placenta. 24471554 0 16 theme placenta 116:123 arg1 moieties 59:66 carbohydrate moieties 46:66 carbohydrate moieties 46:66 Intermediate filament proteins expression and carbohydrate moieties in trophoblast and decidual cells of mature cat placenta. 24471554 0 17 from moieties 59:66 arg1 cells 96:100 trophoblast and decidual cells 71:100 cells 96:100 Intermediate filament proteins expression and carbohydrate moieties in trophoblast and decidual cells of mature cat placenta. 24471554 8 18 theme branched 1216:1223 arg1 Oligosaccharides 1132:1147 Oligosaccharides 1132:1147 Oligosaccharides bound by Phaseolus vulgaris erythroagglutinin 1132:1193 Oligosaccharides bound by Phaseolus vulgaris erythroagglutinin were the only highly branched N-linked residues evidenced in cats, and they were restricted to the syncytium. 24471554 8 18 theme branched 1216:1223 arg1 residues 1234:1241 the only highly branched N-linked residues 1200:1241 the only highly branched N-linked residues evidenced in cats 1200:1259 Oligosaccharides bound by Phaseolus vulgaris erythroagglutinin were the only highly branched N-linked residues evidenced in cats, and they were restricted to the syncytium. 24471554 7 19 theme galactose 1084:1092 arg1 oligomers 1121:1129 non-sialylated galactose and N-acetyl galactosamine oligomers 1069:1129 non-sialylated galactose and N-acetyl galactosamine oligomers 1069:1129 Trophoblast expressed a broad population of glycans, highly exposing terminal N-acetyl glucosamine residues and non-sialylated galactose and N-acetyl galactosamine oligomers. 24471554 2 20 theme gestation 395:403 arg1 days 387:390 45 ± 5 days 380:390 45 ± 5 days of gestation 380:403 Samples from 12 normal pregnant female cats, after 45 ± 5 days of gestation, were obtained removing the uterine horns by hysterectomy. 24471554 4 21 theme glycosides 715:724 arg1 profile 737:743 glycosides expression profile 715:743 glycosides expression profile 715:743 In addition, lectin histochemistry was performed using a panel of several biotinylated lectins to characterize glycosides expression profile. 24471554 0 22 theme cat 112:114 arg1 placenta 116:123 mature cat placenta 105:123 mature cat placenta 105:123 Intermediate filament proteins expression and carbohydrate moieties in trophoblast and decidual cells of mature cat placenta. 24471554 10 23 theme embryo-maternal 1575:1589 arg1 dialogue 1591:1598 the embryo-maternal dialogue 1571:1598 the embryo-maternal dialogue 1571:1598 Glycosylation of proteins determines many of their final properties, thus becoming essential for the embryo-maternal dialogue during implantation and placentation. 24471554 11 24 from pregnancies 1705:1715 arg1 species 1726:1732 other species 1720:1732 other species 1720:1732 Changes in glycosylation pattern have been related to pathological pregnancies in other species. 24471554 1 25 theme cytoskeletal 168:179 arg1 proteins 203:210 cytoskeletal intermediate filament proteins 168:210 cytoskeletal intermediate filament proteins 168:210 The aim of this study was to characterize cytoskeletal intermediate filament proteins and glycoconjugates of syncytiotrophoblast, cytotrophoblast and decidual cells of feline endotheliochorial placenta. 24471554 6 26 with consistent 898:907 arg1 origin 920:925 their origin 914:925 their origin from endometrial fibroblasts 914:954 Decidual cells were only positive to vimentin, consistent with their origin from endometrial fibroblasts. 24471554 8 27 theme vulgaris 1168:1175 arg1 erythroagglutinin 1177:1193 Phaseolus vulgaris erythroagglutinin 1158:1193 Phaseolus vulgaris erythroagglutinin 1158:1193 Oligosaccharides bound by Phaseolus vulgaris erythroagglutinin were the only highly branched N-linked residues evidenced in cats, and they were restricted to the syncytium. 24471554 12 28 gly glycosylation 1762:1774 arg1 placenta 1802:1809 the normal cat placenta 1787:1809 the normal cat placenta 1787:1809 Hence, the knowledge about glycosylation profile of the normal cat placenta may lead to a better understanding of both normal and pathological reproductive events. 24471554 2 29 theme pregnant 352:359 arg1 cats 368:371 12 normal pregnant female cats 342:371 12 normal pregnant female cats 342:371 Samples from 12 normal pregnant female cats, after 45 ± 5 days of gestation, were obtained removing the uterine horns by hysterectomy. 24471554 1 30 theme intermediate 181:192 arg1 filament 194:201 intermediate filament 181:201 cytoskeletal intermediate filament proteins 168:210 The aim of this study was to characterize cytoskeletal intermediate filament proteins and glycoconjugates of syncytiotrophoblast, cytotrophoblast and decidual cells of feline endotheliochorial placenta. 24471554 0 31 theme Intermediate 0:11 arg1 filament 13:20 Intermediate filament 0:20 Intermediate filament 0:20 Intermediate filament proteins expression and carbohydrate moieties in trophoblast and decidual cells of mature cat placenta. 24471554 1 32 theme endotheliochorial 301:317 arg1 placenta 319:326 feline endotheliochorial placenta 294:326 feline endotheliochorial placenta 294:326 The aim of this study was to characterize cytoskeletal intermediate filament proteins and glycoconjugates of syncytiotrophoblast, cytotrophoblast and decidual cells of feline endotheliochorial placenta. 24471554 8 33 theme N-linked 1225:1232 arg1 Oligosaccharides 1132:1147 Oligosaccharides 1132:1147 Oligosaccharides bound by Phaseolus vulgaris erythroagglutinin 1132:1193 Oligosaccharides bound by Phaseolus vulgaris erythroagglutinin were the only highly branched N-linked residues evidenced in cats, and they were restricted to the syncytium. 24471554 8 33 theme N-linked 1225:1232 arg1 residues 1234:1241 the only highly branched N-linked residues 1200:1241 the only highly branched N-linked residues evidenced in cats 1200:1259 Oligosaccharides bound by Phaseolus vulgaris erythroagglutinin were the only highly branched N-linked residues evidenced in cats, and they were restricted to the syncytium. 24471554 7 34 theme N-acetyl 1035:1042 arg1 residues 1056:1063 terminal N-acetyl glucosamine residues and non-sialylated galactose and N-acetyl galactosamine oligomers 1026:1129 residues 1056:1063 Trophoblast expressed a broad population of glycans, highly exposing terminal N-acetyl glucosamine residues and non-sialylated galactose and N-acetyl galactosamine oligomers. 24471554 2 35 theme normal 345:350 arg1 cats 368:371 12 normal pregnant female cats 342:371 12 normal pregnant female cats 342:371 Samples from 12 normal pregnant female cats, after 45 ± 5 days of gestation, were obtained removing the uterine horns by hysterectomy. 24471554 1 36 theme filament 194:201 arg1 proteins 203:210 cytoskeletal intermediate filament proteins 168:210 cytoskeletal intermediate filament proteins 168:210 The aim of this study was to characterize cytoskeletal intermediate filament proteins and glycoconjugates of syncytiotrophoblast, cytotrophoblast and decidual cells of feline endotheliochorial placenta. 24471554 7 37 gly non-sialylated 1069:1082 arg1 oligomers 1121:1129 non-sialylated galactose and N-acetyl galactosamine oligomers 1069:1129 non-sialylated galactose and N-acetyl galactosamine oligomers 1069:1129 Trophoblast expressed a broad population of glycans, highly exposing terminal N-acetyl glucosamine residues and non-sialylated galactose and N-acetyl galactosamine oligomers. 24471554 1 38 theme placenta 319:326 arg1 cytotrophoblast 256:270 cytotrophoblast 256:270 cytotrophoblast 256:270 The aim of this study was to characterize cytoskeletal intermediate filament proteins and glycoconjugates of syncytiotrophoblast, cytotrophoblast and decidual cells of feline endotheliochorial placenta. 24471554 1 38 theme placenta 319:326 arg1 cells 285:289 decidual cells 276:289 decidual cells 276:289 The aim of this study was to characterize cytoskeletal intermediate filament proteins and glycoconjugates of syncytiotrophoblast, cytotrophoblast and decidual cells of feline endotheliochorial placenta. 24471554 1 38 theme placenta 319:326 arg1 syncytiotrophoblast 235:253 syncytiotrophoblast 235:253 syncytiotrophoblast 235:253 The aim of this study was to characterize cytoskeletal intermediate filament proteins and glycoconjugates of syncytiotrophoblast, cytotrophoblast and decidual cells of feline endotheliochorial placenta. 24471554 7 39 theme glucosamine 1044:1054 arg1 residues 1056:1063 terminal N-acetyl glucosamine residues and non-sialylated galactose and N-acetyl galactosamine oligomers 1026:1129 residues 1056:1063 Trophoblast expressed a broad population of glycans, highly exposing terminal N-acetyl glucosamine residues and non-sialylated galactose and N-acetyl galactosamine oligomers. 24471554 2 40 theme uterine 433:439 arg1 horns 441:445 the uterine horns 429:445 the uterine horns 429:445 Samples from 12 normal pregnant female cats, after 45 ± 5 days of gestation, were obtained removing the uterine horns by hysterectomy. 24471554 9 41 theme lectin 1357:1362 arg1 affinity 1364:1371 lectin affinity 1357:1371 lectin affinity of decidual cells 1357:1389 Unlike results reported on humans, mice and rats on lectin affinity of decidual cells, sialid acids and complex N-linked oligosaccharides were not demonstrated in cats. 24471554 12 42 theme placenta 1802:1809 arg1 profile 1776:1782 glycosylation profile 1762:1782 glycosylation profile of the normal cat placenta 1762:1809 Hence, the knowledge about glycosylation profile of the normal cat placenta may lead to a better understanding of both normal and pathological reproductive events. 24471554 10 43 gly Glycosylation 1474:1486 arg1 proteins 1491:1498 proteins 1491:1498 proteins 1491:1498 Glycosylation of proteins determines many of their final properties, thus becoming essential for the embryo-maternal dialogue during implantation and placentation. 24471554 9 44 link N-linked 1417:1424 arg1 oligosaccharides 1426:1441 complex N-linked oligosaccharides 1409:1441 complex N-linked oligosaccharides 1409:1441 Unlike results reported on humans, mice and rats on lectin affinity of decidual cells, sialid acids and complex N-linked oligosaccharides were not demonstrated in cats. 24471554 4 45 theme several 670:676 arg1 lectins 691:697 several biotinylated lectins 670:697 several biotinylated lectins 670:697 In addition, lectin histochemistry was performed using a panel of several biotinylated lectins to characterize glycosides expression profile. 24471554 0 46 theme carbohydrate 46:57 arg1 moieties 59:66 carbohydrate moieties 46:66 carbohydrate moieties 46:66 Intermediate filament proteins expression and carbohydrate moieties in trophoblast and decidual cells of mature cat placenta. 24471554 12 47 theme cat 1798:1800 arg1 placenta 1802:1809 the normal cat placenta 1787:1809 the normal cat placenta 1787:1809 Hence, the knowledge about glycosylation profile of the normal cat placenta may lead to a better understanding of both normal and pathological reproductive events. 24471554 9 48 theme decidual 1376:1383 arg1 cells 1385:1389 decidual cells 1376:1389 decidual cells 1376:1389 Unlike results reported on humans, mice and rats on lectin affinity of decidual cells, sialid acids and complex N-linked oligosaccharides were not demonstrated in cats. 24471554 4 49 theme expression 726:735 arg1 profile 737:743 glycosides expression profile 715:743 glycosides expression profile 715:743 In addition, lectin histochemistry was performed using a panel of several biotinylated lectins to characterize glycosides expression profile. 24471554 12 50 theme glycosylation 1762:1774 arg1 profile 1776:1782 glycosylation profile 1762:1782 glycosylation profile of the normal cat placenta 1762:1809 Hence, the knowledge about glycosylation profile of the normal cat placenta may lead to a better understanding of both normal and pathological reproductive events. 24471554 4 51 theme lectin 617:622 arg1 histochemistry 624:637 lectin histochemistry 617:637 lectin histochemistry 617:637 In addition, lectin histochemistry was performed using a panel of several biotinylated lectins to characterize glycosides expression profile. 24471554 9 52 theme cells 1385:1389 arg1 affinity 1364:1371 lectin affinity 1357:1371 lectin affinity of decidual cells 1357:1389 Unlike results reported on humans, mice and rats on lectin affinity of decidual cells, sialid acids and complex N-linked oligosaccharides were not demonstrated in cats. 24471554 12 53 theme better 1825:1830 arg1 understanding 1832:1844 a better understanding 1823:1844 a better understanding of both normal and pathological reproductive events 1823:1896 Hence, the knowledge about glycosylation profile of the normal cat placenta may lead to a better understanding of both normal and pathological reproductive events. 24471554 4 54 theme lectins 691:697 arg1 panel 661:665 a panel 659:665 a panel of several biotinylated lectins to characterize glycosides expression profile 659:743 In addition, lectin histochemistry was performed using a panel of several biotinylated lectins to characterize glycosides expression profile. 24471554 6 55 from fibroblasts 944:954 arg1 origin 920:925 their origin 914:925 their origin from endometrial fibroblasts 914:954 Decidual cells were only positive to vimentin, consistent with their origin from endometrial fibroblasts. 24471554 5 56 theme acidic 820:825 arg1 cytokeratins 837:848 acidic and basic cytokeratins 820:848 acidic and basic cytokeratins 820:848 Cytotrophoblast and syncytiotrophoblast showed immunoreactivity only with acidic and basic cytokeratins. 24471554 8 57 link N-linked 1225:1232 arg1 Oligosaccharides 1132:1147 Oligosaccharides 1132:1147 Oligosaccharides bound by Phaseolus vulgaris erythroagglutinin 1132:1193 Oligosaccharides bound by Phaseolus vulgaris erythroagglutinin were the only highly branched N-linked residues evidenced in cats, and they were restricted to the syncytium. 24471554 8 57 link N-linked 1225:1232 arg1 residues 1234:1241 the only highly branched N-linked residues 1200:1241 the only highly branched N-linked residues evidenced in cats 1200:1259 Oligosaccharides bound by Phaseolus vulgaris erythroagglutinin were the only highly branched N-linked residues evidenced in cats, and they were restricted to the syncytium. 24471554 11 58 from Changes 1638:1644 arg1 pattern 1663:1669 glycosylation pattern 1649:1669 glycosylation pattern 1649:1669 Changes in glycosylation pattern have been related to pathological pregnancies in other species. 24471554 10 59 theme proteins 1491:1498 arg1 Glycosylation 1474:1486 Glycosylation 1474:1486 Glycosylation of proteins 1474:1498 Glycosylation of proteins determines many of their final properties, thus becoming essential for the embryo-maternal dialogue during implantation and placentation. 24471554 9 60 theme N-linked 1417:1424 arg1 oligosaccharides 1426:1441 complex N-linked oligosaccharides 1409:1441 complex N-linked oligosaccharides 1409:1441 Unlike results reported on humans, mice and rats on lectin affinity of decidual cells, sialid acids and complex N-linked oligosaccharides were not demonstrated in cats. 24471554 9 61 theme sialid 1392:1397 arg1 acids 1399:1403 sialid acids 1392:1403 sialid acids 1392:1403 Unlike results reported on humans, mice and rats on lectin affinity of decidual cells, sialid acids and complex N-linked oligosaccharides were not demonstrated in cats. 24471554 12 62 theme normal 1854:1859 arg1 events 1891:1896 both normal and pathological reproductive events 1849:1896 both normal and pathological reproductive events 1849:1896 Hence, the knowledge about glycosylation profile of the normal cat placenta may lead to a better understanding of both normal and pathological reproductive events. 24471554 6 63 theme Decidual 851:858 arg1 cells 860:864 Decidual cells 851:864 Decidual cells 851:864 Decidual cells were only positive to vimentin, consistent with their origin from endometrial fibroblasts. 24471554 8 64 theme Phaseolus 1158:1166 arg1 erythroagglutinin 1177:1193 Phaseolus vulgaris erythroagglutinin 1158:1193 Phaseolus vulgaris erythroagglutinin 1158:1193 Oligosaccharides bound by Phaseolus vulgaris erythroagglutinin were the only highly branched N-linked residues evidenced in cats, and they were restricted to the syncytium. 24471554 6 65 theme endometrial 932:942 arg1 fibroblasts 944:954 endometrial fibroblasts 932:954 endometrial fibroblasts 932:954 Decidual cells were only positive to vimentin, consistent with their origin from endometrial fibroblasts. 24471554 3 66 theme routine 492:498 arg1 observation 500:510 routine observation 492:510 routine observation 492:510 Sections were processed for routine observation and for immunohistochemistry using anticytokeratin, antivimentin and antidesmin antibodies. 24471554 7 67 theme terminal 1026:1033 arg1 residues 1056:1063 terminal N-acetyl glucosamine residues and non-sialylated galactose and N-acetyl galactosamine oligomers 1026:1129 residues 1056:1063 Trophoblast expressed a broad population of glycans, highly exposing terminal N-acetyl glucosamine residues and non-sialylated galactose and N-acetyl galactosamine oligomers. 24471554 1 68 theme syncytiotrophoblast 235:253 arg1 glycoconjugates 216:230 glycoconjugates 216:230 glycoconjugates of syncytiotrophoblast, cytotrophoblast and decidual cells of feline endotheliochorial placenta 216:326 The aim of this study was to characterize cytoskeletal intermediate filament proteins and glycoconjugates of syncytiotrophoblast, cytotrophoblast and decidual cells of feline endotheliochorial placenta. 24471554 1 68 theme syncytiotrophoblast 235:253 arg1 proteins 203:210 cytoskeletal intermediate filament proteins 168:210 cytoskeletal intermediate filament proteins 168:210 The aim of this study was to characterize cytoskeletal intermediate filament proteins and glycoconjugates of syncytiotrophoblast, cytotrophoblast and decidual cells of feline endotheliochorial placenta. 24471554 12 69 theme normal 1791:1796 arg1 placenta 1802:1809 the normal cat placenta 1787:1809 the normal cat placenta 1787:1809 Hence, the knowledge about glycosylation profile of the normal cat placenta may lead to a better understanding of both normal and pathological reproductive events. 24471554 10 70 theme final 1525:1529 arg1 properties 1531:1540 their final properties 1519:1540 their final properties 1519:1540 Glycosylation of proteins determines many of their final properties, thus becoming essential for the embryo-maternal dialogue during implantation and placentation. 24471554 2 71 theme female 361:366 arg1 cats 368:371 12 normal pregnant female cats 342:371 12 normal pregnant female cats 342:371 Samples from 12 normal pregnant female cats, after 45 ± 5 days of gestation, were obtained removing the uterine horns by hysterectomy. 24471554 11 72 theme glycosylation 1649:1661 arg1 pattern 1663:1669 glycosylation pattern 1649:1669 glycosylation pattern 1649:1669 Changes in glycosylation pattern have been related to pathological pregnancies in other species. 24471554 9 73 theme complex 1409:1415 arg1 oligosaccharides 1426:1441 complex N-linked oligosaccharides 1409:1441 complex N-linked oligosaccharides 1409:1441 Unlike results reported on humans, mice and rats on lectin affinity of decidual cells, sialid acids and complex N-linked oligosaccharides were not demonstrated in cats. 24471554 4 74 theme biotinylated 678:689 arg1 lectins 691:697 several biotinylated lectins 670:697 several biotinylated lectins 670:697 In addition, lectin histochemistry was performed using a panel of several biotinylated lectins to characterize glycosides expression profile. 24471554 12 75 theme events 1891:1896 arg1 understanding 1832:1844 a better understanding 1823:1844 a better understanding of both normal and pathological reproductive events 1823:1896 Hence, the knowledge about glycosylation profile of the normal cat placenta may lead to a better understanding of both normal and pathological reproductive events. 24471554 1 76 theme cytotrophoblast 256:270 arg1 glycoconjugates 216:230 glycoconjugates 216:230 glycoconjugates of syncytiotrophoblast, cytotrophoblast and decidual cells of feline endotheliochorial placenta 216:326 The aim of this study was to characterize cytoskeletal intermediate filament proteins and glycoconjugates of syncytiotrophoblast, cytotrophoblast and decidual cells of feline endotheliochorial placenta. 24471554 1 76 theme cytotrophoblast 256:270 arg1 proteins 203:210 cytoskeletal intermediate filament proteins 168:210 cytoskeletal intermediate filament proteins 168:210 The aim of this study was to characterize cytoskeletal intermediate filament proteins and glycoconjugates of syncytiotrophoblast, cytotrophoblast and decidual cells of feline endotheliochorial placenta. 24471554 0 77 theme trophoblast 71:81 arg1 cells 96:100 trophoblast and decidual cells 71:100 cells 96:100 Intermediate filament proteins expression and carbohydrate moieties in trophoblast and decidual cells of mature cat placenta. 24471554 0 78 from expression 31:40 arg1 cells 96:100 trophoblast and decidual cells 71:100 cells 96:100 Intermediate filament proteins expression and carbohydrate moieties in trophoblast and decidual cells of mature cat placenta. 24471554 7 79 theme galactosamine 1107:1119 arg1 oligomers 1121:1129 non-sialylated galactose and N-acetyl galactosamine oligomers 1069:1129 non-sialylated galactose and N-acetyl galactosamine oligomers 1069:1129 Trophoblast expressed a broad population of glycans, highly exposing terminal N-acetyl glucosamine residues and non-sialylated galactose and N-acetyl galactosamine oligomers. 24471554 1 80 theme study 142:146 arg1 aim 130:132 The aim 126:132 The aim of this study 126:146 The aim of this study was to characterize cytoskeletal intermediate filament proteins and glycoconjugates of syncytiotrophoblast, cytotrophoblast and decidual cells of feline endotheliochorial placenta. 24471554 11 81 theme pathological 1692:1703 arg1 pregnancies 1705:1715 pathological pregnancies 1692:1715 pathological pregnancies in other species 1692:1732 Changes in glycosylation pattern have been related to pathological pregnancies in other species. 24471554 5 82 theme basic 831:835 arg1 cytokeratins 837:848 acidic and basic cytokeratins 820:848 acidic and basic cytokeratins 820:848 Cytotrophoblast and syncytiotrophoblast showed immunoreactivity only with acidic and basic cytokeratins. 28792526 9 0 theme modifications 1585:1597 arg1 significance 1544:1555 The significance 1540:1555 The significance of these post-translational modifications 1540:1597 The significance of these post-translational modifications is discussed with regards to the function of these proteins and the design of serological tests and vaccines. 28792526 2 1 theme Ser- 393:396 arg1 Gp40 426:429 Gp40 426:429 Gp40 426:429 C. parvum vaccine candidates, which are on the surface of sporozoites, include glycoproteins with Ser- and Thr-rich domains (Gp15, Gp40, and Gp900) and a low complexity, acidic protein (Cp23). 28792526 2 1 theme Ser- 393:396 arg1 Gp900 436:440 Gp900 436:440 Gp900 436:440 C. parvum vaccine candidates, which are on the surface of sporozoites, include glycoproteins with Ser- and Thr-rich domains (Gp15, Gp40, and Gp900) and a low complexity, acidic protein (Cp23). 28792526 2 1 theme Ser- 393:396 arg1 Gp15 420:423 Gp15 420:423 Gp15 420:423 C. parvum vaccine candidates, which are on the surface of sporozoites, include glycoproteins with Ser- and Thr-rich domains (Gp15, Gp40, and Gp900) and a low complexity, acidic protein (Cp23). 28792526 2 1 theme Ser- 393:396 arg1 domains 411:417 Ser- and Thr-rich domains 393:417 Ser- and Thr-rich domains (Gp15, Gp40, and Gp900) 393:441 C. parvum vaccine candidates, which are on the surface of sporozoites, include glycoproteins with Ser- and Thr-rich domains (Gp15, Gp40, and Gp900) and a low complexity, acidic protein (Cp23). 28792526 3 2 theme novel 700:704 arg1 Gp20 692:695 Gp20 692:695 Gp20 692:695 Here we used mass spectrometry to determine that O-linked GalNAc is present in dense arrays on a glycopeptide with consecutive Ser derived from Gp40 and on glycopeptides with consecutive Thr derived from Gp20, a novel C. parvum glycoprotein with a formula weight of ~20 kDa. 28792526 3 2 theme novel 700:704 arg1 glycoprotein 716:727 a novel C. parvum glycoprotein 698:727 a novel C. parvum glycoprotein with a formula weight of ~20 kDa 698:760 Here we used mass spectrometry to determine that O-linked GalNAc is present in dense arrays on a glycopeptide with consecutive Ser derived from Gp40 and on glycopeptides with consecutive Thr derived from Gp20, a novel C. parvum glycoprotein with a formula weight of ~20 kDa. 28792526 6 3 theme parvum 1146:1151 arg1 candidates 1161:1170 C. parvum vaccine candidates 1143:1170 C. parvum vaccine candidates 1143:1170 In summary, C. parvum O-GalNAc transferases, which are homologs of host enzymes, densely modify arrays of Ser or Thr, as well as isolated Ser and Thr residues on C. parvum vaccine candidates. 28792526 3 4 theme O-linked 537:544 arg1 GalNAc 546:551 O-linked GalNAc 537:551 O-linked GalNAc 537:551 Here we used mass spectrometry to determine that O-linked GalNAc is present in dense arrays on a glycopeptide with consecutive Ser derived from Gp40 and on glycopeptides with consecutive Thr derived from Gp20, a novel C. parvum glycoprotein with a formula weight of ~20 kDa. 28792526 3 5 attach derived 679:685 arg2 Thr 675:677 consecutive Thr 663:677 consecutive Thr derived from Gp20, a novel C. parvum glycoprotein with a formula weight of ~20 kDa 663:760 Here we used mass spectrometry to determine that O-linked GalNAc is present in dense arrays on a glycopeptide with consecutive Ser derived from Gp40 and on glycopeptides with consecutive Thr derived from Gp20, a novel C. parvum glycoprotein with a formula weight of ~20 kDa. 28792526 3 5 attach derived 679:685 arg1 Gp20 692:695 Gp20 692:695 Gp20 692:695 Here we used mass spectrometry to determine that O-linked GalNAc is present in dense arrays on a glycopeptide with consecutive Ser derived from Gp40 and on glycopeptides with consecutive Thr derived from Gp20, a novel C. parvum glycoprotein with a formula weight of ~20 kDa. 28792526 3 5 attach derived 679:685 arg1 glycoprotein 716:727 a novel C. parvum glycoprotein 698:727 a novel C. parvum glycoprotein with a formula weight of ~20 kDa 698:760 Here we used mass spectrometry to determine that O-linked GalNAc is present in dense arrays on a glycopeptide with consecutive Ser derived from Gp40 and on glycopeptides with consecutive Thr derived from Gp20, a novel C. parvum glycoprotein with a formula weight of ~20 kDa. 28792526 4 6 theme Thr 796:798 arg1 residues 800:807 the occupied Ser or Thr residues 776:807 the occupied Ser or Thr residues in glycopeptides from Gp15 and Gp900 776:844 In contrast, the occupied Ser or Thr residues in glycopeptides from Gp15 and Gp900 are isolated from one another. 28792526 8 7 gly glycopeptides 1347:1359 arg2 glycopeptides 1347:1359 glycopeptides 1347:1359 glycopeptides with O-glycans 1347:1374 Mass spectrometric demonstration here of glycopeptides with O-glycans complements previous identification C. parvum O-GalNAc transferases, lectin binding to vaccine candidates, and human and mouse antibodies binding to glycopeptides. 28792526 6 8 theme Thr 1127:1129 arg1 residues 1131:1138 isolated Ser and Thr residues 1110:1138 isolated Ser and Thr residues on C. parvum vaccine candidates 1110:1170 In summary, C. parvum O-GalNAc transferases, which are homologs of host enzymes, densely modify arrays of Ser or Thr, as well as isolated Ser and Thr residues on C. parvum vaccine candidates. 28792526 7 9 theme other 1276:1280 arg1 parasites 1295:1303 other apicomplexan parasites 1276:1303 other apicomplexan parasites 1276:1303 The N-terminus of an immunodominant antigen has lipid modifications similar to those of host cells and other apicomplexan parasites. 28792526 3 10 theme parvum 709:714 arg1 Gp20 692:695 Gp20 692:695 Gp20 692:695 Here we used mass spectrometry to determine that O-linked GalNAc is present in dense arrays on a glycopeptide with consecutive Ser derived from Gp40 and on glycopeptides with consecutive Thr derived from Gp20, a novel C. parvum glycoprotein with a formula weight of ~20 kDa. 28792526 3 10 theme parvum 709:714 arg1 glycoprotein 716:727 a novel C. parvum glycoprotein 698:727 a novel C. parvum glycoprotein with a formula weight of ~20 kDa 698:760 Here we used mass spectrometry to determine that O-linked GalNAc is present in dense arrays on a glycopeptide with consecutive Ser derived from Gp40 and on glycopeptides with consecutive Thr derived from Gp20, a novel C. parvum glycoprotein with a formula weight of ~20 kDa. 28792526 1 11 theme diarrhea 245:252 arg1 hominis 213:219 Cryptosporidium hominis 197:219 Cryptosporidium hominis 197:219 Cryptosporidium parvum (studied here) and Cryptosporidium hominis are important causes of diarrhea in infants and immunosuppressed persons. 28792526 1 11 theme diarrhea 245:252 arg1 causes 235:240 important causes 225:240 important causes of diarrhea in infants and immunosuppressed persons 225:292 Cryptosporidium parvum (studied here) and Cryptosporidium hominis are important causes of diarrhea in infants and immunosuppressed persons. 28792526 1 11 theme diarrhea 245:252 arg1 parvum 171:176 Cryptosporidium parvum 155:176 Cryptosporidium parvum (studied here) 155:191 Cryptosporidium parvum (studied here) and Cryptosporidium hominis are important causes of diarrhea in infants and immunosuppressed persons. 28792526 9 12 theme proteins 1650:1657 arg1 design 1667:1672 the design 1663:1672 the design of serological tests and vaccines 1663:1706 The significance of these post-translational modifications is discussed with regards to the function of these proteins and the design of serological tests and vaccines. 28792526 9 12 theme proteins 1650:1657 arg1 function 1632:1639 the function 1628:1639 the function of these proteins 1628:1657 The significance of these post-translational modifications is discussed with regards to the function of these proteins and the design of serological tests and vaccines. 28792526 6 13 theme isolated 1110:1117 arg1 residues 1131:1138 isolated Ser and Thr residues 1110:1138 isolated Ser and Thr residues on C. parvum vaccine candidates 1110:1170 In summary, C. parvum O-GalNAc transferases, which are homologs of host enzymes, densely modify arrays of Ser or Thr, as well as isolated Ser and Thr residues on C. parvum vaccine candidates. 28792526 3 14 theme formula 736:742 arg1 weight 744:749 a formula weight 734:749 a formula weight of ~20 kDa 734:760 Here we used mass spectrometry to determine that O-linked GalNAc is present in dense arrays on a glycopeptide with consecutive Ser derived from Gp40 and on glycopeptides with consecutive Thr derived from Gp20, a novel C. parvum glycoprotein with a formula weight of ~20 kDa. 28792526 2 15 theme vaccine 305:311 arg1 candidates 313:322 C. parvum vaccine candidates 295:322 C. parvum vaccine candidates 295:322 C. parvum vaccine candidates, which are on the surface of sporozoites, include glycoproteins with Ser- and Thr-rich domains (Gp15, Gp40, and Gp900) and a low complexity, acidic protein (Cp23). 28792526 9 16 theme tests 1689:1693 arg1 design 1667:1672 the design 1663:1672 the design of serological tests and vaccines 1663:1706 The significance of these post-translational modifications is discussed with regards to the function of these proteins and the design of serological tests and vaccines. 28792526 9 16 theme tests 1689:1693 arg1 function 1632:1639 the function 1628:1639 the function of these proteins 1628:1657 The significance of these post-translational modifications is discussed with regards to the function of these proteins and the design of serological tests and vaccines. 28792526 8 17 theme identification 1397:1410 arg1 transferases 1431:1442 previous identification C. parvum O-GalNAc transferases 1388:1442 previous identification C. parvum O-GalNAc transferases 1388:1442 Mass spectrometric demonstration here of glycopeptides with O-glycans complements previous identification C. parvum O-GalNAc transferases, lectin binding to vaccine candidates, and human and mouse antibodies binding to glycopeptides. 28792526 3 18 theme kDa 758:760 arg1 weight 744:749 a formula weight 734:749 a formula weight of ~20 kDa 734:760 Here we used mass spectrometry to determine that O-linked GalNAc is present in dense arrays on a glycopeptide with consecutive Ser derived from Gp40 and on glycopeptides with consecutive Thr derived from Gp20, a novel C. parvum glycoprotein with a formula weight of ~20 kDa. 28792526 9 19 theme vaccines 1699:1706 arg1 design 1667:1672 the design 1663:1672 the design of serological tests and vaccines 1663:1706 The significance of these post-translational modifications is discussed with regards to the function of these proteins and the design of serological tests and vaccines. 28792526 9 19 theme vaccines 1699:1706 arg1 function 1632:1639 the function 1628:1639 the function of these proteins 1628:1657 The significance of these post-translational modifications is discussed with regards to the function of these proteins and the design of serological tests and vaccines. 28792526 8 20 theme parvum 1415:1420 arg1 transferases 1431:1442 previous identification C. parvum O-GalNAc transferases 1388:1442 previous identification C. parvum O-GalNAc transferases 1388:1442 Mass spectrometric demonstration here of glycopeptides with O-glycans complements previous identification C. parvum O-GalNAc transferases, lectin binding to vaccine candidates, and human and mouse antibodies binding to glycopeptides. 28792526 6 21 from Thr 1094:1096 arg1 candidates 1161:1170 C. parvum vaccine candidates 1143:1170 C. parvum vaccine candidates 1143:1170 In summary, C. parvum O-GalNAc transferases, which are homologs of host enzymes, densely modify arrays of Ser or Thr, as well as isolated Ser and Thr residues on C. parvum vaccine candidates. 28792526 8 22 theme lectin 1445:1450 arg1 binding 1452:1458 lectin binding 1445:1458 lectin binding to vaccine candidates 1445:1480 Mass spectrometric demonstration here of glycopeptides with O-glycans complements previous identification C. parvum O-GalNAc transferases, lectin binding to vaccine candidates, and human and mouse antibodies binding to glycopeptides. 28792526 2 23 dep domains 411:417 arg1 Gp40 426:429 Gp40 426:429 Gp40 426:429 C. parvum vaccine candidates, which are on the surface of sporozoites, include glycoproteins with Ser- and Thr-rich domains (Gp15, Gp40, and Gp900) and a low complexity, acidic protein (Cp23). 28792526 2 23 dep domains 411:417 arg1 Gp900 436:440 Gp900 436:440 Gp900 436:440 C. parvum vaccine candidates, which are on the surface of sporozoites, include glycoproteins with Ser- and Thr-rich domains (Gp15, Gp40, and Gp900) and a low complexity, acidic protein (Cp23). 28792526 2 23 dep domains 411:417 arg1 Gp15 420:423 Gp15 420:423 Gp15 420:423 C. parvum vaccine candidates, which are on the surface of sporozoites, include glycoproteins with Ser- and Thr-rich domains (Gp15, Gp40, and Gp900) and a low complexity, acidic protein (Cp23). 28792526 2 23 dep domains 411:417 arg1 domains 411:417 Ser- and Thr-rich domains 393:417 Ser- and Thr-rich domains (Gp15, Gp40, and Gp900) 393:441 C. parvum vaccine candidates, which are on the surface of sporozoites, include glycoproteins with Ser- and Thr-rich domains (Gp15, Gp40, and Gp900) and a low complexity, acidic protein (Cp23). 28792526 6 24 from arrays 1077:1082 arg1 candidates 1161:1170 C. parvum vaccine candidates 1143:1170 C. parvum vaccine candidates 1143:1170 In summary, C. parvum O-GalNAc transferases, which are homologs of host enzymes, densely modify arrays of Ser or Thr, as well as isolated Ser and Thr residues on C. parvum vaccine candidates. 28792526 4 25 dep one 864:866 arg1 another 868:874 another 868:874 another 868:874 In contrast, the occupied Ser or Thr residues in glycopeptides from Gp15 and Gp900 are isolated from one another. 28792526 7 26 theme lipid 1221:1225 arg1 modifications 1227:1239 lipid modifications 1221:1239 lipid modifications similar to those of host cells and other apicomplexan parasites 1221:1303 The N-terminus of an immunodominant antigen has lipid modifications similar to those of host cells and other apicomplexan parasites. 28792526 6 27 from Ser 1087:1089 arg1 candidates 1161:1170 C. parvum vaccine candidates 1143:1170 C. parvum vaccine candidates 1143:1170 In summary, C. parvum O-GalNAc transferases, which are homologs of host enzymes, densely modify arrays of Ser or Thr, as well as isolated Ser and Thr residues on C. parvum vaccine candidates. 28792526 0 28 theme Cryptosporidium 0:14 arg1 parvum 16:21 Cryptosporidium parvum 0:21 Cryptosporidium parvum vaccine candidates 0:40 Cryptosporidium parvum vaccine candidates are incompletely modified with O-linked-N-acetylgalactosamine or contain N-terminal N-myristate and S-palmitate. 28792526 7 29 contain has 1217:1219 arg2 modifications 1227:1239 lipid modifications 1221:1239 lipid modifications similar to those of host cells and other apicomplexan parasites 1221:1303 The N-terminus of an immunodominant antigen has lipid modifications similar to those of host cells and other apicomplexan parasites. 28792526 7 29 contain has 1217:1219 arg1 N-terminus 1177:1186 The N-terminus 1173:1186 The N-terminus of an immunodominant antigen 1173:1215 The N-terminus of an immunodominant antigen has lipid modifications similar to those of host cells and other apicomplexan parasites. 28792526 7 30 theme antigen 1209:1215 arg1 N-terminus 1177:1186 The N-terminus 1173:1186 The N-terminus of an immunodominant antigen 1173:1215 The N-terminus of an immunodominant antigen has lipid modifications similar to those of host cells and other apicomplexan parasites. 28792526 3 31 from arrays 573:578 arg1 present 556:562 present 556:562 present 556:562 Here we used mass spectrometry to determine that O-linked GalNAc is present in dense arrays on a glycopeptide with consecutive Ser derived from Gp40 and on glycopeptides with consecutive Thr derived from Gp20, a novel C. parvum glycoprotein with a formula weight of ~20 kDa. 28792526 0 32 theme vaccine 23:29 arg1 candidates 31:40 Cryptosporidium parvum vaccine candidates 0:40 Cryptosporidium parvum vaccine candidates 0:40 Cryptosporidium parvum vaccine candidates are incompletely modified with O-linked-N-acetylgalactosamine or contain N-terminal N-myristate and S-palmitate. 28792526 4 33 attach isolated 850:857 arg1 one 864:866 one 864:866 one 864:866 In contrast, the occupied Ser or Thr residues in glycopeptides from Gp15 and Gp900 are isolated from one another. 28792526 4 33 attach isolated 850:857 arg2 residues 800:807 the occupied Ser or Thr residues 776:807 the occupied Ser or Thr residues in glycopeptides from Gp15 and Gp900 776:844 In contrast, the occupied Ser or Thr residues in glycopeptides from Gp15 and Gp900 are isolated from one another. 28792526 3 34 located present 556:562 arg2 GalNAc 546:551 O-linked GalNAc 537:551 O-linked GalNAc 537:551 Here we used mass spectrometry to determine that O-linked GalNAc is present in dense arrays on a glycopeptide with consecutive Ser derived from Gp40 and on glycopeptides with consecutive Thr derived from Gp20, a novel C. parvum glycoprotein with a formula weight of ~20 kDa. 28792526 3 34 located present 556:562 arg1 glycopeptide 585:596 a glycopeptide 583:596 a glycopeptide with consecutive Ser derived from Gp40 583:635 Here we used mass spectrometry to determine that O-linked GalNAc is present in dense arrays on a glycopeptide with consecutive Ser derived from Gp40 and on glycopeptides with consecutive Thr derived from Gp20, a novel C. parvum glycoprotein with a formula weight of ~20 kDa. 28792526 3 34 located present 556:562 arg1 arrays 573:578 dense arrays 567:578 dense arrays 567:578 Here we used mass spectrometry to determine that O-linked GalNAc is present in dense arrays on a glycopeptide with consecutive Ser derived from Gp40 and on glycopeptides with consecutive Thr derived from Gp20, a novel C. parvum glycoprotein with a formula weight of ~20 kDa. 28792526 5 35 theme amino 949:953 arg1 acid 955:958 the second amino acid 938:958 the second amino acid 938:958 Gly at the N-terminus of Cp23 is N-myristoylated, while Cys, the second amino acid, is S-palmitoylated. 28792526 5 35 theme amino 949:953 arg1 Cys 933:935 Cys 933:935 Cys 933:935 Gly at the N-terminus of Cp23 is N-myristoylated, while Cys, the second amino acid, is S-palmitoylated. 28792526 2 36 theme acidic 465:470 arg1 Cp23 481:484 Cp23 481:484 Cp23 481:484 C. parvum vaccine candidates, which are on the surface of sporozoites, include glycoproteins with Ser- and Thr-rich domains (Gp15, Gp40, and Gp900) and a low complexity, acidic protein (Cp23). 28792526 2 36 theme acidic 465:470 arg1 complexity 453:462 a low complexity 447:462 a low complexity 447:462 C. parvum vaccine candidates, which are on the surface of sporozoites, include glycoproteins with Ser- and Thr-rich domains (Gp15, Gp40, and Gp900) and a low complexity, acidic protein (Cp23). 28792526 2 36 theme acidic 465:470 arg1 protein 472:478 acidic protein 465:478 acidic protein (Cp23) 465:485 C. parvum vaccine candidates, which are on the surface of sporozoites, include glycoproteins with Ser- and Thr-rich domains (Gp15, Gp40, and Gp900) and a low complexity, acidic protein (Cp23). 28792526 2 37 gly glycoproteins 374:386 arg1 glycoproteins 374:386 glycoproteins 374:386 glycoproteins with Ser- and Thr-rich domains (Gp15, Gp40, and Gp900) and a low complexity, acidic protein (Cp23) 374:485 C. parvum vaccine candidates, which are on the surface of sporozoites, include glycoproteins with Ser- and Thr-rich domains (Gp15, Gp40, and Gp900) and a low complexity, acidic protein (Cp23). 28792526 4 38 theme Ser 789:791 arg1 residues 800:807 the occupied Ser or Thr residues 776:807 the occupied Ser or Thr residues in glycopeptides from Gp15 and Gp900 776:844 In contrast, the occupied Ser or Thr residues in glycopeptides from Gp15 and Gp900 are isolated from one another. 28792526 6 39 theme Thr 1094:1096 arg1 arrays 1077:1082 arrays 1077:1082 arrays of Ser or Thr, as well as isolated Ser and Thr residues on C. parvum vaccine candidates 1077:1170 In summary, C. parvum O-GalNAc transferases, which are homologs of host enzymes, densely modify arrays of Ser or Thr, as well as isolated Ser and Thr residues on C. parvum vaccine candidates. 28792526 3 40 theme consecutive 663:673 arg1 Thr 675:677 consecutive Thr 663:677 consecutive Thr derived from Gp20, a novel C. parvum glycoprotein with a formula weight of ~20 kDa 663:760 Here we used mass spectrometry to determine that O-linked GalNAc is present in dense arrays on a glycopeptide with consecutive Ser derived from Gp40 and on glycopeptides with consecutive Thr derived from Gp20, a novel C. parvum glycoprotein with a formula weight of ~20 kDa. 28792526 3 41 used used 496:499 arg2 we 493:494 we 493:494 we 493:494 Here we used mass spectrometry to determine that O-linked GalNAc is present in dense arrays on a glycopeptide with consecutive Ser derived from Gp40 and on glycopeptides with consecutive Thr derived from Gp20, a novel C. parvum glycoprotein with a formula weight of ~20 kDa. 28792526 8 42 gly glycopeptides 1525:1537 arg2 glycopeptides 1525:1537 glycopeptides 1525:1537 glycopeptides 1525:1537 Mass spectrometric demonstration here of glycopeptides with O-glycans complements previous identification C. parvum O-GalNAc transferases, lectin binding to vaccine candidates, and human and mouse antibodies binding to glycopeptides. 28792526 8 43 with glycopeptides 1347:1359 arg1 O-glycans 1366:1374 O-glycans 1366:1374 O-glycans 1366:1374 Mass spectrometric demonstration here of glycopeptides with O-glycans complements previous identification C. parvum O-GalNAc transferases, lectin binding to vaccine candidates, and human and mouse antibodies binding to glycopeptides. 28792526 3 44 theme mass 501:504 arg1 spectrometry 506:517 mass spectrometry 501:517 mass spectrometry 501:517 Here we used mass spectrometry to determine that O-linked GalNAc is present in dense arrays on a glycopeptide with consecutive Ser derived from Gp40 and on glycopeptides with consecutive Thr derived from Gp20, a novel C. parvum glycoprotein with a formula weight of ~20 kDa. 28792526 9 45 theme post-translational 1566:1583 arg1 modifications 1585:1597 these post-translational modifications 1560:1597 these post-translational modifications 1560:1597 The significance of these post-translational modifications is discussed with regards to the function of these proteins and the design of serological tests and vaccines. 28792526 6 46 from residues 1131:1138 arg1 candidates 1161:1170 C. parvum vaccine candidates 1143:1170 C. parvum vaccine candidates 1143:1170 In summary, C. parvum O-GalNAc transferases, which are homologs of host enzymes, densely modify arrays of Ser or Thr, as well as isolated Ser and Thr residues on C. parvum vaccine candidates. 28792526 6 47 theme O-GalNAc 1003:1010 arg1 homologs 1036:1043 homologs 1036:1043 homologs of host enzymes 1036:1059 In summary, C. parvum O-GalNAc transferases, which are homologs of host enzymes, densely modify arrays of Ser or Thr, as well as isolated Ser and Thr residues on C. parvum vaccine candidates. 28792526 6 47 theme O-GalNAc 1003:1010 arg1 transferases 1012:1023 C. parvum O-GalNAc transferases 993:1023 C. parvum O-GalNAc transferases 993:1023 In summary, C. parvum O-GalNAc transferases, which are homologs of host enzymes, densely modify arrays of Ser or Thr, as well as isolated Ser and Thr residues on C. parvum vaccine candidates. 28792526 6 48 theme vaccine 1153:1159 arg1 candidates 1161:1170 C. parvum vaccine candidates 1143:1170 C. parvum vaccine candidates 1143:1170 In summary, C. parvum O-GalNAc transferases, which are homologs of host enzymes, densely modify arrays of Ser or Thr, as well as isolated Ser and Thr residues on C. parvum vaccine candidates. 28792526 6 49 theme Ser 1087:1089 arg1 arrays 1077:1082 arrays 1077:1082 arrays of Ser or Thr, as well as isolated Ser and Thr residues on C. parvum vaccine candidates 1077:1170 In summary, C. parvum O-GalNAc transferases, which are homologs of host enzymes, densely modify arrays of Ser or Thr, as well as isolated Ser and Thr residues on C. parvum vaccine candidates. 28792526 3 50 theme C. 706:707 arg1 Gp20 692:695 Gp20 692:695 Gp20 692:695 Here we used mass spectrometry to determine that O-linked GalNAc is present in dense arrays on a glycopeptide with consecutive Ser derived from Gp40 and on glycopeptides with consecutive Thr derived from Gp20, a novel C. parvum glycoprotein with a formula weight of ~20 kDa. 28792526 3 50 theme C. 706:707 arg1 glycoprotein 716:727 a novel C. parvum glycoprotein 698:727 a novel C. parvum glycoprotein with a formula weight of ~20 kDa 698:760 Here we used mass spectrometry to determine that O-linked GalNAc is present in dense arrays on a glycopeptide with consecutive Ser derived from Gp40 and on glycopeptides with consecutive Thr derived from Gp20, a novel C. parvum glycoprotein with a formula weight of ~20 kDa. 28792526 3 51 with glycopeptides 644:656 arg1 Thr 675:677 consecutive Thr 663:677 consecutive Thr derived from Gp20, a novel C. parvum glycoprotein with a formula weight of ~20 kDa 663:760 Here we used mass spectrometry to determine that O-linked GalNAc is present in dense arrays on a glycopeptide with consecutive Ser derived from Gp40 and on glycopeptides with consecutive Thr derived from Gp20, a novel C. parvum glycoprotein with a formula weight of ~20 kDa. 28792526 4 52 gly glycopeptides 812:824 arg1 Gp900 840:844 Gp900 840:844 Gp900 840:844 In contrast, the occupied Ser or Thr residues in glycopeptides from Gp15 and Gp900 are isolated from one another. 28792526 4 52 gly glycopeptides 812:824 arg1 Gp15 831:834 Gp15 831:834 Gp15 831:834 In contrast, the occupied Ser or Thr residues in glycopeptides from Gp15 and Gp900 are isolated from one another. 28792526 4 52 gly glycopeptides 812:824 arg2 glycopeptides 812:824 glycopeptides 812:824 glycopeptides from Gp15 and Gp900 812:844 In contrast, the occupied Ser or Thr residues in glycopeptides from Gp15 and Gp900 are isolated from one another. 28792526 6 53 theme residues 1131:1138 arg1 arrays 1077:1082 arrays 1077:1082 arrays of Ser or Thr, as well as isolated Ser and Thr residues on C. parvum vaccine candidates 1077:1170 In summary, C. parvum O-GalNAc transferases, which are homologs of host enzymes, densely modify arrays of Ser or Thr, as well as isolated Ser and Thr residues on C. parvum vaccine candidates. 28792526 2 54 theme sporozoites 353:363 arg1 surface 342:348 the surface 338:348 the surface of sporozoites 338:363 C. parvum vaccine candidates, which are on the surface of sporozoites, include glycoproteins with Ser- and Thr-rich domains (Gp15, Gp40, and Gp900) and a low complexity, acidic protein (Cp23). 28792526 1 55 theme important 225:233 arg1 hominis 213:219 Cryptosporidium hominis 197:219 Cryptosporidium hominis 197:219 Cryptosporidium parvum (studied here) and Cryptosporidium hominis are important causes of diarrhea in infants and immunosuppressed persons. 28792526 1 55 theme important 225:233 arg1 causes 235:240 important causes 225:240 important causes of diarrhea in infants and immunosuppressed persons 225:292 Cryptosporidium parvum (studied here) and Cryptosporidium hominis are important causes of diarrhea in infants and immunosuppressed persons. 28792526 1 55 theme important 225:233 arg1 parvum 171:176 Cryptosporidium parvum 155:176 Cryptosporidium parvum (studied here) 155:191 Cryptosporidium parvum (studied here) and Cryptosporidium hominis are important causes of diarrhea in infants and immunosuppressed persons. 28792526 3 56 gly glycopeptide 585:596 arg2 glycopeptide 585:596 a glycopeptide 583:596 a glycopeptide with consecutive Ser derived from Gp40 583:635 Here we used mass spectrometry to determine that O-linked GalNAc is present in dense arrays on a glycopeptide with consecutive Ser derived from Gp40 and on glycopeptides with consecutive Thr derived from Gp20, a novel C. parvum glycoprotein with a formula weight of ~20 kDa. 28792526 6 57 theme enzymes 1053:1059 arg1 homologs 1036:1043 homologs 1036:1043 homologs of host enzymes 1036:1059 In summary, C. parvum O-GalNAc transferases, which are homologs of host enzymes, densely modify arrays of Ser or Thr, as well as isolated Ser and Thr residues on C. parvum vaccine candidates. 28792526 6 57 theme enzymes 1053:1059 arg1 transferases 1012:1023 C. parvum O-GalNAc transferases 993:1023 C. parvum O-GalNAc transferases 993:1023 In summary, C. parvum O-GalNAc transferases, which are homologs of host enzymes, densely modify arrays of Ser or Thr, as well as isolated Ser and Thr residues on C. parvum vaccine candidates. 28792526 6 58 theme Ser 1119:1121 arg1 residues 1131:1138 isolated Ser and Thr residues 1110:1138 isolated Ser and Thr residues on C. parvum vaccine candidates 1110:1170 In summary, C. parvum O-GalNAc transferases, which are homologs of host enzymes, densely modify arrays of Ser or Thr, as well as isolated Ser and Thr residues on C. parvum vaccine candidates. 28792526 3 59 theme dense 567:571 arg1 arrays 573:578 dense arrays 567:578 dense arrays 567:578 Here we used mass spectrometry to determine that O-linked GalNAc is present in dense arrays on a glycopeptide with consecutive Ser derived from Gp40 and on glycopeptides with consecutive Thr derived from Gp20, a novel C. parvum glycoprotein with a formula weight of ~20 kDa. 28792526 3 60 attach derived 619:625 arg2 Ser 615:617 consecutive Ser 603:617 consecutive Ser derived from Gp40 603:635 Here we used mass spectrometry to determine that O-linked GalNAc is present in dense arrays on a glycopeptide with consecutive Ser derived from Gp40 and on glycopeptides with consecutive Thr derived from Gp20, a novel C. parvum glycoprotein with a formula weight of ~20 kDa. 28792526 3 60 attach derived 619:625 arg1 Gp40 632:635 Gp40 632:635 Gp40 632:635 Here we used mass spectrometry to determine that O-linked GalNAc is present in dense arrays on a glycopeptide with consecutive Ser derived from Gp40 and on glycopeptides with consecutive Thr derived from Gp20, a novel C. parvum glycoprotein with a formula weight of ~20 kDa. 28792526 8 61 theme previous 1388:1395 arg1 transferases 1431:1442 previous identification C. parvum O-GalNAc transferases 1388:1442 previous identification C. parvum O-GalNAc transferases 1388:1442 Mass spectrometric demonstration here of glycopeptides with O-glycans complements previous identification C. parvum O-GalNAc transferases, lectin binding to vaccine candidates, and human and mouse antibodies binding to glycopeptides. 28792526 7 62 theme host 1261:1264 arg1 cells 1266:1270 host cells 1261:1270 host cells 1261:1270 The N-terminus of an immunodominant antigen has lipid modifications similar to those of host cells and other apicomplexan parasites. 28792526 8 63 theme spectrometric 1311:1323 arg1 demonstration 1325:1337 Mass spectrometric demonstration 1306:1337 Mass spectrometric demonstration 1306:1337 Mass spectrometric demonstration here of glycopeptides with O-glycans complements previous identification C. parvum O-GalNAc transferases, lectin binding to vaccine candidates, and human and mouse antibodies binding to glycopeptides. 28792526 3 64 theme consecutive 603:613 arg1 Ser 615:617 consecutive Ser 603:617 consecutive Ser derived from Gp40 603:635 Here we used mass spectrometry to determine that O-linked GalNAc is present in dense arrays on a glycopeptide with consecutive Ser derived from Gp40 and on glycopeptides with consecutive Thr derived from Gp20, a novel C. parvum glycoprotein with a formula weight of ~20 kDa. 28792526 9 65 theme serological 1677:1687 arg1 tests 1689:1693 serological tests 1677:1693 serological tests 1677:1693 The significance of these post-translational modifications is discussed with regards to the function of these proteins and the design of serological tests and vaccines. 28792526 8 66 theme C. 1412:1413 arg1 transferases 1431:1442 previous identification C. parvum O-GalNAc transferases 1388:1442 previous identification C. parvum O-GalNAc transferases 1388:1442 Mass spectrometric demonstration here of glycopeptides with O-glycans complements previous identification C. parvum O-GalNAc transferases, lectin binding to vaccine candidates, and human and mouse antibodies binding to glycopeptides. 28792526 3 67 from present 556:562 arg1 arrays 573:578 dense arrays 567:578 dense arrays 567:578 Here we used mass spectrometry to determine that O-linked GalNAc is present in dense arrays on a glycopeptide with consecutive Ser derived from Gp40 and on glycopeptides with consecutive Thr derived from Gp20, a novel C. parvum glycoprotein with a formula weight of ~20 kDa. 28792526 3 68 with glycopeptide 585:596 arg1 Ser 615:617 consecutive Ser 603:617 consecutive Ser derived from Gp40 603:635 Here we used mass spectrometry to determine that O-linked GalNAc is present in dense arrays on a glycopeptide with consecutive Ser derived from Gp40 and on glycopeptides with consecutive Thr derived from Gp20, a novel C. parvum glycoprotein with a formula weight of ~20 kDa. 28792526 4 69 from Gp900 840:844 arg1 residues 800:807 the occupied Ser or Thr residues 776:807 the occupied Ser or Thr residues in glycopeptides from Gp15 and Gp900 776:844 In contrast, the occupied Ser or Thr residues in glycopeptides from Gp15 and Gp900 are isolated from one another. 28792526 4 69 from Gp900 840:844 arg1 glycopeptides 812:824 glycopeptides 812:824 glycopeptides from Gp15 and Gp900 812:844 In contrast, the occupied Ser or Thr residues in glycopeptides from Gp15 and Gp900 are isolated from one another. 28792526 2 70 theme parvum 298:303 arg1 candidates 313:322 C. parvum vaccine candidates 295:322 C. parvum vaccine candidates 295:322 C. parvum vaccine candidates, which are on the surface of sporozoites, include glycoproteins with Ser- and Thr-rich domains (Gp15, Gp40, and Gp900) and a low complexity, acidic protein (Cp23). 28792526 1 71 from causes 235:240 arg1 persons 286:292 immunosuppressed persons 269:292 immunosuppressed persons 269:292 Cryptosporidium parvum (studied here) and Cryptosporidium hominis are important causes of diarrhea in infants and immunosuppressed persons. 28792526 1 71 from causes 235:240 arg1 infants 257:263 infants 257:263 infants 257:263 Cryptosporidium parvum (studied here) and Cryptosporidium hominis are important causes of diarrhea in infants and immunosuppressed persons. 28792526 8 72 theme O-GalNAc 1422:1429 arg1 transferases 1431:1442 previous identification C. parvum O-GalNAc transferases 1388:1442 previous identification C. parvum O-GalNAc transferases 1388:1442 Mass spectrometric demonstration here of glycopeptides with O-glycans complements previous identification C. parvum O-GalNAc transferases, lectin binding to vaccine candidates, and human and mouse antibodies binding to glycopeptides. 28792526 7 73 theme similar 1241:1247 arg1 modifications 1227:1239 lipid modifications 1221:1239 lipid modifications similar to those of host cells and other apicomplexan parasites 1221:1303 The N-terminus of an immunodominant antigen has lipid modifications similar to those of host cells and other apicomplexan parasites. 28792526 0 74 theme N-terminal 115:124 arg1 N-myristate 126:136 N-terminal N-myristate 115:136 N-terminal N-myristate 115:136 Cryptosporidium parvum vaccine candidates are incompletely modified with O-linked-N-acetylgalactosamine or contain N-terminal N-myristate and S-palmitate. 28792526 4 75 from Gp15 831:834 arg1 residues 800:807 the occupied Ser or Thr residues 776:807 the occupied Ser or Thr residues in glycopeptides from Gp15 and Gp900 776:844 In contrast, the occupied Ser or Thr residues in glycopeptides from Gp15 and Gp900 are isolated from one another. 28792526 4 75 from Gp15 831:834 arg1 glycopeptides 812:824 glycopeptides 812:824 glycopeptides from Gp15 and Gp900 812:844 In contrast, the occupied Ser or Thr residues in glycopeptides from Gp15 and Gp900 are isolated from one another. 28792526 5 76 theme Cp23 902:905 arg1 N-terminus 888:897 the N-terminus 884:897 the N-terminus of Cp23 884:905 Gly at the N-terminus of Cp23 is N-myristoylated, while Cys, the second amino acid, is S-palmitoylated. 28792526 7 77 theme apicomplexan 1282:1293 arg1 parasites 1295:1303 other apicomplexan parasites 1276:1303 other apicomplexan parasites 1276:1303 The N-terminus of an immunodominant antigen has lipid modifications similar to those of host cells and other apicomplexan parasites. 28792526 4 78 from residues 800:807 arg1 Gp900 840:844 Gp900 840:844 Gp900 840:844 In contrast, the occupied Ser or Thr residues in glycopeptides from Gp15 and Gp900 are isolated from one another. 28792526 4 78 from residues 800:807 arg1 Gp15 831:834 Gp15 831:834 Gp15 831:834 In contrast, the occupied Ser or Thr residues in glycopeptides from Gp15 and Gp900 are isolated from one another. 28792526 4 78 from residues 800:807 arg1 glycopeptides 812:824 glycopeptides 812:824 glycopeptides from Gp15 and Gp900 812:844 In contrast, the occupied Ser or Thr residues in glycopeptides from Gp15 and Gp900 are isolated from one another. 28792526 3 79 attach present 556:562 arg1 glycopeptides 644:656 glycopeptides 644:656 glycopeptides with consecutive Thr derived from Gp20, a novel C. parvum glycoprotein with a formula weight of ~20 kDa 644:760 Here we used mass spectrometry to determine that O-linked GalNAc is present in dense arrays on a glycopeptide with consecutive Ser derived from Gp40 and on glycopeptides with consecutive Thr derived from Gp20, a novel C. parvum glycoprotein with a formula weight of ~20 kDa. 28792526 3 79 attach present 556:562 arg2 GalNAc 546:551 O-linked GalNAc 537:551 O-linked GalNAc 537:551 Here we used mass spectrometry to determine that O-linked GalNAc is present in dense arrays on a glycopeptide with consecutive Ser derived from Gp40 and on glycopeptides with consecutive Thr derived from Gp20, a novel C. parvum glycoprotein with a formula weight of ~20 kDa. 28792526 3 79 attach present 556:562 arg1 glycopeptide 585:596 a glycopeptide 583:596 a glycopeptide with consecutive Ser derived from Gp40 583:635 Here we used mass spectrometry to determine that O-linked GalNAc is present in dense arrays on a glycopeptide with consecutive Ser derived from Gp40 and on glycopeptides with consecutive Thr derived from Gp20, a novel C. parvum glycoprotein with a formula weight of ~20 kDa. 28792526 3 79 attach present 556:562 arg1 arrays 573:578 dense arrays 567:578 dense arrays 567:578 Here we used mass spectrometry to determine that O-linked GalNAc is present in dense arrays on a glycopeptide with consecutive Ser derived from Gp40 and on glycopeptides with consecutive Thr derived from Gp20, a novel C. parvum glycoprotein with a formula weight of ~20 kDa. 28792526 6 80 theme parvum 996:1001 arg1 homologs 1036:1043 homologs 1036:1043 homologs of host enzymes 1036:1059 In summary, C. parvum O-GalNAc transferases, which are homologs of host enzymes, densely modify arrays of Ser or Thr, as well as isolated Ser and Thr residues on C. parvum vaccine candidates. 28792526 6 80 theme parvum 996:1001 arg1 transferases 1012:1023 C. parvum O-GalNAc transferases 993:1023 C. parvum O-GalNAc transferases 993:1023 In summary, C. parvum O-GalNAc transferases, which are homologs of host enzymes, densely modify arrays of Ser or Thr, as well as isolated Ser and Thr residues on C. parvum vaccine candidates. 28792526 3 81 link O-linked 537:544 arg1 GalNAc 546:551 O-linked GalNAc 537:551 O-linked GalNAc 537:551 Here we used mass spectrometry to determine that O-linked GalNAc is present in dense arrays on a glycopeptide with consecutive Ser derived from Gp40 and on glycopeptides with consecutive Thr derived from Gp20, a novel C. parvum glycoprotein with a formula weight of ~20 kDa. 28792526 3 82 gly glycoprotein 716:727 arg1 Gp20 692:695 Gp20 692:695 Gp20 692:695 Here we used mass spectrometry to determine that O-linked GalNAc is present in dense arrays on a glycopeptide with consecutive Ser derived from Gp40 and on glycopeptides with consecutive Thr derived from Gp20, a novel C. parvum glycoprotein with a formula weight of ~20 kDa. 28792526 3 82 gly glycoprotein 716:727 arg1 glycoprotein 716:727 a novel C. parvum glycoprotein 698:727 a novel C. parvum glycoprotein with a formula weight of ~20 kDa 698:760 Here we used mass spectrometry to determine that O-linked GalNAc is present in dense arrays on a glycopeptide with consecutive Ser derived from Gp40 and on glycopeptides with consecutive Thr derived from Gp20, a novel C. parvum glycoprotein with a formula weight of ~20 kDa. 28792526 0 83 theme parvum 16:21 arg1 candidates 31:40 Cryptosporidium parvum vaccine candidates 0:40 Cryptosporidium parvum vaccine candidates 0:40 Cryptosporidium parvum vaccine candidates are incompletely modified with O-linked-N-acetylgalactosamine or contain N-terminal N-myristate and S-palmitate. 28792526 3 84 with glycoprotein 716:727 arg1 weight 744:749 a formula weight 734:749 a formula weight of ~20 kDa 734:760 Here we used mass spectrometry to determine that O-linked GalNAc is present in dense arrays on a glycopeptide with consecutive Ser derived from Gp40 and on glycopeptides with consecutive Thr derived from Gp20, a novel C. parvum glycoprotein with a formula weight of ~20 kDa. 28792526 7 85 theme immunodominant 1194:1207 arg1 antigen 1209:1215 an immunodominant antigen 1191:1215 an immunodominant antigen 1191:1215 The N-terminus of an immunodominant antigen has lipid modifications similar to those of host cells and other apicomplexan parasites. 28792526 2 86 theme low 449:451 arg1 complexity 453:462 a low complexity 447:462 a low complexity 447:462 C. parvum vaccine candidates, which are on the surface of sporozoites, include glycoproteins with Ser- and Thr-rich domains (Gp15, Gp40, and Gp900) and a low complexity, acidic protein (Cp23). 28792526 2 86 theme low 449:451 arg1 protein 472:478 acidic protein 465:478 acidic protein (Cp23) 465:485 C. parvum vaccine candidates, which are on the surface of sporozoites, include glycoproteins with Ser- and Thr-rich domains (Gp15, Gp40, and Gp900) and a low complexity, acidic protein (Cp23). 28792526 0 87 mod modified 59:66 arg3 O-linked-N-acetylgalactosamine 73:102 O-linked-N-acetylgalactosamine 73:102 O-linked-N-acetylgalactosamine 73:102 Cryptosporidium parvum vaccine candidates are incompletely modified with O-linked-N-acetylgalactosamine or contain N-terminal N-myristate and S-palmitate. 28792526 0 87 mod modified 59:66 arg1 candidates 31:40 Cryptosporidium parvum vaccine candidates 0:40 Cryptosporidium parvum vaccine candidates 0:40 Cryptosporidium parvum vaccine candidates are incompletely modified with O-linked-N-acetylgalactosamine or contain N-terminal N-myristate and S-palmitate. 28792526 8 88 theme human 1487:1491 arg1 antibodies 1503:1512 human and mouse antibodies 1487:1512 antibodies 1503:1512 Mass spectrometric demonstration here of glycopeptides with O-glycans complements previous identification C. parvum O-GalNAc transferases, lectin binding to vaccine candidates, and human and mouse antibodies binding to glycopeptides. 28792526 5 89 theme second 942:947 arg1 acid 955:958 the second amino acid 938:958 the second amino acid 938:958 Gly at the N-terminus of Cp23 is N-myristoylated, while Cys, the second amino acid, is S-palmitoylated. 28792526 5 89 theme second 942:947 arg1 Cys 933:935 Cys 933:935 Cys 933:935 Gly at the N-terminus of Cp23 is N-myristoylated, while Cys, the second amino acid, is S-palmitoylated. 28792526 8 90 theme mouse 1497:1501 arg1 antibodies 1503:1512 human and mouse antibodies 1487:1512 antibodies 1503:1512 Mass spectrometric demonstration here of glycopeptides with O-glycans complements previous identification C. parvum O-GalNAc transferases, lectin binding to vaccine candidates, and human and mouse antibodies binding to glycopeptides. 28792526 2 91 with glycoproteins 374:386 arg1 Gp40 426:429 Gp40 426:429 Gp40 426:429 C. parvum vaccine candidates, which are on the surface of sporozoites, include glycoproteins with Ser- and Thr-rich domains (Gp15, Gp40, and Gp900) and a low complexity, acidic protein (Cp23). 28792526 2 91 with glycoproteins 374:386 arg1 complexity 453:462 a low complexity 447:462 a low complexity 447:462 C. parvum vaccine candidates, which are on the surface of sporozoites, include glycoproteins with Ser- and Thr-rich domains (Gp15, Gp40, and Gp900) and a low complexity, acidic protein (Cp23). 28792526 2 91 with glycoproteins 374:386 arg1 domains 411:417 Ser- and Thr-rich domains 393:417 Ser- and Thr-rich domains (Gp15, Gp40, and Gp900) 393:441 C. parvum vaccine candidates, which are on the surface of sporozoites, include glycoproteins with Ser- and Thr-rich domains (Gp15, Gp40, and Gp900) and a low complexity, acidic protein (Cp23). 28792526 2 91 with glycoproteins 374:386 arg1 Gp900 436:440 Gp900 436:440 Gp900 436:440 C. parvum vaccine candidates, which are on the surface of sporozoites, include glycoproteins with Ser- and Thr-rich domains (Gp15, Gp40, and Gp900) and a low complexity, acidic protein (Cp23). 28792526 2 91 with glycoproteins 374:386 arg1 protein 472:478 acidic protein 465:478 acidic protein (Cp23) 465:485 C. parvum vaccine candidates, which are on the surface of sporozoites, include glycoproteins with Ser- and Thr-rich domains (Gp15, Gp40, and Gp900) and a low complexity, acidic protein (Cp23). 28792526 2 91 with glycoproteins 374:386 arg1 Gp15 420:423 Gp15 420:423 Gp15 420:423 C. parvum vaccine candidates, which are on the surface of sporozoites, include glycoproteins with Ser- and Thr-rich domains (Gp15, Gp40, and Gp900) and a low complexity, acidic protein (Cp23). 28792526 8 92 theme vaccine 1463:1469 arg1 candidates 1471:1480 vaccine candidates 1463:1480 vaccine candidates 1463:1480 Mass spectrometric demonstration here of glycopeptides with O-glycans complements previous identification C. parvum O-GalNAc transferases, lectin binding to vaccine candidates, and human and mouse antibodies binding to glycopeptides. 28792526 6 93 theme host 1048:1051 arg1 enzymes 1053:1059 host enzymes 1048:1059 host enzymes 1048:1059 In summary, C. parvum O-GalNAc transferases, which are homologs of host enzymes, densely modify arrays of Ser or Thr, as well as isolated Ser and Thr residues on C. parvum vaccine candidates. 28792526 4 94 theme occupied 780:787 arg1 residues 800:807 the occupied Ser or Thr residues 776:807 the occupied Ser or Thr residues in glycopeptides from Gp15 and Gp900 776:844 In contrast, the occupied Ser or Thr residues in glycopeptides from Gp15 and Gp900 are isolated from one another. 28792526 5 95 from N-terminus 888:897 arg1 Gly 877:879 Gly 877:879 Gly at the N-terminus of Cp23 877:905 Gly at the N-terminus of Cp23 is N-myristoylated, while Cys, the second amino acid, is S-palmitoylated. 28792526 8 96 theme Mass 1306:1309 arg1 demonstration 1325:1337 Mass spectrometric demonstration 1306:1337 Mass spectrometric demonstration 1306:1337 Mass spectrometric demonstration here of glycopeptides with O-glycans complements previous identification C. parvum O-GalNAc transferases, lectin binding to vaccine candidates, and human and mouse antibodies binding to glycopeptides. 28792526 0 97 contain contain 107:113 arg1 candidates 31:40 Cryptosporidium parvum vaccine candidates 0:40 Cryptosporidium parvum vaccine candidates 0:40 Cryptosporidium parvum vaccine candidates are incompletely modified with O-linked-N-acetylgalactosamine or contain N-terminal N-myristate and S-palmitate. 28792526 0 97 contain contain 107:113 arg2 N-myristate 126:136 N-terminal N-myristate 115:136 N-terminal N-myristate 115:136 Cryptosporidium parvum vaccine candidates are incompletely modified with O-linked-N-acetylgalactosamine or contain N-terminal N-myristate and S-palmitate. 28792526 0 97 contain contain 107:113 arg2 S-palmitate 142:152 S-palmitate 142:152 S-palmitate 142:152 Cryptosporidium parvum vaccine candidates are incompletely modified with O-linked-N-acetylgalactosamine or contain N-terminal N-myristate and S-palmitate. 28792526 1 98 theme immunosuppressed 269:284 arg1 persons 286:292 immunosuppressed persons 269:292 immunosuppressed persons 269:292 Cryptosporidium parvum (studied here) and Cryptosporidium hominis are important causes of diarrhea in infants and immunosuppressed persons. 28792526 3 99 gly glycopeptides 644:656 arg2 glycopeptides 644:656 glycopeptides 644:656 glycopeptides with consecutive Thr derived from Gp20, a novel C. parvum glycoprotein with a formula weight of ~20 kDa 644:760 Here we used mass spectrometry to determine that O-linked GalNAc is present in dense arrays on a glycopeptide with consecutive Ser derived from Gp40 and on glycopeptides with consecutive Thr derived from Gp20, a novel C. parvum glycoprotein with a formula weight of ~20 kDa. 28792526 2 100 theme Thr-rich 402:409 arg1 Gp40 426:429 Gp40 426:429 Gp40 426:429 C. parvum vaccine candidates, which are on the surface of sporozoites, include glycoproteins with Ser- and Thr-rich domains (Gp15, Gp40, and Gp900) and a low complexity, acidic protein (Cp23). 28792526 2 100 theme Thr-rich 402:409 arg1 Gp900 436:440 Gp900 436:440 Gp900 436:440 C. parvum vaccine candidates, which are on the surface of sporozoites, include glycoproteins with Ser- and Thr-rich domains (Gp15, Gp40, and Gp900) and a low complexity, acidic protein (Cp23). 28792526 2 100 theme Thr-rich 402:409 arg1 Gp15 420:423 Gp15 420:423 Gp15 420:423 C. parvum vaccine candidates, which are on the surface of sporozoites, include glycoproteins with Ser- and Thr-rich domains (Gp15, Gp40, and Gp900) and a low complexity, acidic protein (Cp23). 28792526 2 100 theme Thr-rich 402:409 arg1 domains 411:417 Ser- and Thr-rich domains 393:417 Ser- and Thr-rich domains (Gp15, Gp40, and Gp900) 393:441 C. parvum vaccine candidates, which are on the surface of sporozoites, include glycoproteins with Ser- and Thr-rich domains (Gp15, Gp40, and Gp900) and a low complexity, acidic protein (Cp23). 28792526 6 101 from candidates 1161:1170 arg1 arrays 1077:1082 arrays 1077:1082 arrays of Ser or Thr, as well as isolated Ser and Thr residues on C. parvum vaccine candidates 1077:1170 In summary, C. parvum O-GalNAc transferases, which are homologs of host enzymes, densely modify arrays of Ser or Thr, as well as isolated Ser and Thr residues on C. parvum vaccine candidates. 28726377 5 0 gly glycosylated 922:933 arg1 peptides 945:952 Several glycosylated signaling peptides 914:952 Several glycosylated signaling peptides with multiple glycoforms 914:977 Several glycosylated signaling peptides with multiple glycoforms are identified, including the first report of glycosylated insulin-B chain and insulin-C peptide and BigLEN. 28726377 2 1 gly glycoproteins 324:336 arg1 glycoproteins 324:336 glycoproteins 324:336 glycoproteins 324:336 Despite growing interest in glycoproteins, little attention has been directed to glycosylated signaling peptides, largely due to lack of enabling analytical tools. 28726377 3 2 theme signaling 534:542 arg1 peptides 544:551 the signaling peptides 530:551 the signaling peptides extracted from mouse and human pancreatic islets 530:600 Here we explore the occurrence of naturally O-linked glycosylation on the signaling peptides extracted from mouse and human pancreatic islets using mass spectrometry (MS). 28726377 1 3 theme threonine 264:272 arg1 threonine 264:272 threonine 264:272 threonine 264:272 O-Linked glycosylation often involves the covalent attachment of sugar moieties to the hydroxyl group of serine or threonine on proteins/peptides. 28726377 1 3 theme threonine 264:272 arg1 serine 254:259 serine 254:259 serine 254:259 O-Linked glycosylation often involves the covalent attachment of sugar moieties to the hydroxyl group of serine or threonine on proteins/peptides. 28726377 1 3 theme threonine 264:272 arg1 group 245:249 the hydroxyl group 232:249 the hydroxyl group of serine or threonine on proteins/peptides 232:293 O-Linked glycosylation often involves the covalent attachment of sugar moieties to the hydroxyl group of serine or threonine on proteins/peptides. 28726377 3 4 theme human 578:582 arg1 islets 595:600 human pancreatic islets 578:600 human pancreatic islets 578:600 Here we explore the occurrence of naturally O-linked glycosylation on the signaling peptides extracted from mouse and human pancreatic islets using mass spectrometry (MS). 28726377 4 5 theme signaling 894:902 arg1 peptides 904:911 signaling peptides 894:911 signaling peptides 894:911 A novel targeted MS-based method is developed to increase the likelihood of capturing these modified signaling peptides and to provide improved sequence coverage and accurate glycosite localization, enabling the first large-scale discovery of O-glycosylation on signaling peptides. 28726377 7 6 theme previous 1279:1286 arg1 studies 1288:1294 previous studies 1279:1294 previous studies of glycosylated insulin analogues 1279:1328 Given the importance of insulin and its related peptide hormones and previous studies of glycosylated insulin analogues, this natural glycosylation may provide important insights into diabetes research and therapeutic treatments. 28726377 1 7 theme covalent 191:198 arg1 attachment 200:209 the covalent attachment 187:209 the covalent attachment of sugar moieties to the hydroxyl group of serine or threonine on proteins/peptides 187:293 O-Linked glycosylation often involves the covalent attachment of sugar moieties to the hydroxyl group of serine or threonine on proteins/peptides. 28726377 3 8 theme mass 608:611 arg1 MS 627:628 MS 627:628 MS 627:628 Here we explore the occurrence of naturally O-linked glycosylation on the signaling peptides extracted from mouse and human pancreatic islets using mass spectrometry (MS). 28726377 3 8 theme mass 608:611 arg1 spectrometry 613:624 mass spectrometry 608:624 mass spectrometry (MS) 608:629 Here we explore the occurrence of naturally O-linked glycosylation on the signaling peptides extracted from mouse and human pancreatic islets using mass spectrometry (MS). 28726377 1 9 theme moieties 220:227 arg1 attachment 200:209 the covalent attachment 187:209 the covalent attachment of sugar moieties to the hydroxyl group of serine or threonine on proteins/peptides 187:293 O-Linked glycosylation often involves the covalent attachment of sugar moieties to the hydroxyl group of serine or threonine on proteins/peptides. 28726377 0 10 from Insulin 72:78 arg1 Human 124:128 Human 124:128 Human 124:128 Targeted Mass Spectrometry Approach Enabled Discovery of O-Glycosylated Insulin and Related Signaling Peptides in Mouse and Human Pancreatic Islets. 28726377 0 10 from Insulin 72:78 arg1 Mouse 114:118 Mouse 114:118 Mouse 114:118 Targeted Mass Spectrometry Approach Enabled Discovery of O-Glycosylated Insulin and Related Signaling Peptides in Mouse and Human Pancreatic Islets. 28726377 0 11 from Mouse 114:118 arg1 Discovery 44:52 Discovery 44:52 Discovery of O-Glycosylated Insulin and Related Signaling Peptides in Mouse and Human Pancreatic Islets 44:146 Targeted Mass Spectrometry Approach Enabled Discovery of O-Glycosylated Insulin and Related Signaling Peptides in Mouse and Human Pancreatic Islets. 28726377 1 12 from group 245:249 arg1 proteins/peptides 277:293 proteins/peptides 277:293 proteins/peptides 277:293 O-Linked glycosylation often involves the covalent attachment of sugar moieties to the hydroxyl group of serine or threonine on proteins/peptides. 28726377 2 13 from interest 312:319 arg1 glycoproteins 324:336 glycoproteins 324:336 glycoproteins 324:336 Despite growing interest in glycoproteins, little attention has been directed to glycosylated signaling peptides, largely due to lack of enabling analytical tools. 28726377 0 14 from Peptides 102:109 arg1 Human 124:128 Human 124:128 Human 124:128 Targeted Mass Spectrometry Approach Enabled Discovery of O-Glycosylated Insulin and Related Signaling Peptides in Mouse and Human Pancreatic Islets. 28726377 0 14 from Peptides 102:109 arg1 Mouse 114:118 Mouse 114:118 Mouse 114:118 Targeted Mass Spectrometry Approach Enabled Discovery of O-Glycosylated Insulin and Related Signaling Peptides in Mouse and Human Pancreatic Islets. 28726377 7 15 theme natural 1336:1342 arg1 glycosylation 1344:1356 this natural glycosylation 1331:1356 this natural glycosylation 1331:1356 Given the importance of insulin and its related peptide hormones and previous studies of glycosylated insulin analogues, this natural glycosylation may provide important insights into diabetes research and therapeutic treatments. 28726377 7 16 theme hormones 1266:1273 arg1 studies 1288:1294 previous studies 1279:1294 previous studies of glycosylated insulin analogues 1279:1328 Given the importance of insulin and its related peptide hormones and previous studies of glycosylated insulin analogues, this natural glycosylation may provide important insights into diabetes research and therapeutic treatments. 28726377 7 16 theme hormones 1266:1273 arg1 importance 1220:1229 the importance 1216:1229 the importance of insulin and its related peptide hormones 1216:1273 Given the importance of insulin and its related peptide hormones and previous studies of glycosylated insulin analogues, this natural glycosylation may provide important insights into diabetes research and therapeutic treatments. 28726377 5 17 theme multiple 959:966 arg1 glycoforms 968:977 multiple glycoforms 959:977 multiple glycoforms 959:977 Several glycosylated signaling peptides with multiple glycoforms are identified, including the first report of glycosylated insulin-B chain and insulin-C peptide and BigLEN. 28726377 4 18 theme modified 724:731 arg1 peptides 743:750 these modified signaling peptides 718:750 these modified signaling peptides 718:750 A novel targeted MS-based method is developed to increase the likelihood of capturing these modified signaling peptides and to provide improved sequence coverage and accurate glycosite localization, enabling the first large-scale discovery of O-glycosylation on signaling peptides. 28726377 0 19 theme Related 84:90 arg1 Peptides 102:109 Related Signaling Peptides 84:109 Related Signaling Peptides in Mouse and Human Pancreatic Islets 84:146 Targeted Mass Spectrometry Approach Enabled Discovery of O-Glycosylated Insulin and Related Signaling Peptides in Mouse and Human Pancreatic Islets. 28726377 4 20 theme accurate 798:805 arg1 localization 817:828 accurate glycosite localization 798:828 accurate glycosite localization 798:828 A novel targeted MS-based method is developed to increase the likelihood of capturing these modified signaling peptides and to provide improved sequence coverage and accurate glycosite localization, enabling the first large-scale discovery of O-glycosylation on signaling peptides. 28726377 0 21 theme Peptides 102:109 arg1 Discovery 44:52 Discovery 44:52 Discovery of O-Glycosylated Insulin and Related Signaling Peptides in Mouse and Human Pancreatic Islets 44:146 Targeted Mass Spectrometry Approach Enabled Discovery of O-Glycosylated Insulin and Related Signaling Peptides in Mouse and Human Pancreatic Islets. 28726377 2 22 theme growing 304:310 arg1 interest 312:319 growing interest 304:319 growing interest in glycoproteins 304:336 Despite growing interest in glycoproteins, little attention has been directed to glycosylated signaling peptides, largely due to lack of enabling analytical tools. 28726377 0 23 dep Mouse 114:118 arg1 Islets 141:146 Pancreatic Islets 130:146 Pancreatic Islets 130:146 Targeted Mass Spectrometry Approach Enabled Discovery of O-Glycosylated Insulin and Related Signaling Peptides in Mouse and Human Pancreatic Islets. 28726377 5 24 gly glycosylated 1025:1036 arg1 chain 1048:1052 glycosylated insulin-B chain and insulin-C peptide 1025:1074 chain 1048:1052 Several glycosylated signaling peptides with multiple glycoforms are identified, including the first report of glycosylated insulin-B chain and insulin-C peptide and BigLEN. 28726377 5 25 theme insulin-C 1058:1066 arg1 peptide 1068:1074 glycosylated insulin-B chain and insulin-C peptide 1025:1074 peptide 1068:1074 Several glycosylated signaling peptides with multiple glycoforms are identified, including the first report of glycosylated insulin-B chain and insulin-C peptide and BigLEN. 28726377 4 26 theme improved 767:774 arg1 coverage 785:792 improved sequence coverage 767:792 improved sequence coverage 767:792 A novel targeted MS-based method is developed to increase the likelihood of capturing these modified signaling peptides and to provide improved sequence coverage and accurate glycosite localization, enabling the first large-scale discovery of O-glycosylation on signaling peptides. 28726377 0 27 theme Targeted 0:7 arg1 Approach 27:34 Targeted Mass Spectrometry Approach 0:34 Targeted Mass Spectrometry Approach 0:34 Targeted Mass Spectrometry Approach Enabled Discovery of O-Glycosylated Insulin and Related Signaling Peptides in Mouse and Human Pancreatic Islets. 28726377 2 28 theme analytical 442:451 arg1 tools 453:457 enabling analytical tools 433:457 enabling analytical tools 433:457 Despite growing interest in glycoproteins, little attention has been directed to glycosylated signaling peptides, largely due to lack of enabling analytical tools. 28726377 0 29 theme Spectrometry 14:25 arg1 Approach 27:34 Targeted Mass Spectrometry Approach 0:34 Targeted Mass Spectrometry Approach 0:34 Targeted Mass Spectrometry Approach Enabled Discovery of O-Glycosylated Insulin and Related Signaling Peptides in Mouse and Human Pancreatic Islets. 28726377 5 30 theme glycosylated 1025:1036 arg1 chain 1048:1052 glycosylated insulin-B chain and insulin-C peptide 1025:1074 chain 1048:1052 Several glycosylated signaling peptides with multiple glycoforms are identified, including the first report of glycosylated insulin-B chain and insulin-C peptide and BigLEN. 28726377 0 31 theme Insulin 72:78 arg1 Discovery 44:52 Discovery 44:52 Discovery of O-Glycosylated Insulin and Related Signaling Peptides in Mouse and Human Pancreatic Islets 44:146 Targeted Mass Spectrometry Approach Enabled Discovery of O-Glycosylated Insulin and Related Signaling Peptides in Mouse and Human Pancreatic Islets. 28726377 7 32 theme related 1250:1256 arg1 hormones 1266:1273 its related peptide hormones 1246:1273 its related peptide hormones 1246:1273 Given the importance of insulin and its related peptide hormones and previous studies of glycosylated insulin analogues, this natural glycosylation may provide important insights into diabetes research and therapeutic treatments. 28726377 7 33 theme therapeutic 1416:1426 arg1 treatments 1428:1437 therapeutic treatments 1416:1437 therapeutic treatments 1416:1437 Given the importance of insulin and its related peptide hormones and previous studies of glycosylated insulin analogues, this natural glycosylation may provide important insights into diabetes research and therapeutic treatments. 28726377 1 34 attach attachment 200:209 arg1 threonine 264:272 threonine 264:272 threonine 264:272 O-Linked glycosylation often involves the covalent attachment of sugar moieties to the hydroxyl group of serine or threonine on proteins/peptides. 28726377 1 34 attach attachment 200:209 arg2 moieties 220:227 sugar moieties 214:227 sugar moieties 214:227 O-Linked glycosylation often involves the covalent attachment of sugar moieties to the hydroxyl group of serine or threonine on proteins/peptides. 28726377 1 34 attach attachment 200:209 arg1 serine 254:259 serine 254:259 serine 254:259 O-Linked glycosylation often involves the covalent attachment of sugar moieties to the hydroxyl group of serine or threonine on proteins/peptides. 28726377 1 34 attach attachment 200:209 arg1 group 245:249 the hydroxyl group 232:249 the hydroxyl group of serine or threonine on proteins/peptides 232:293 O-Linked glycosylation often involves the covalent attachment of sugar moieties to the hydroxyl group of serine or threonine on proteins/peptides. 28726377 4 35 theme O-glycosylation 875:889 arg1 discovery 862:870 the first large-scale discovery 840:870 the first large-scale discovery of O-glycosylation 840:889 A novel targeted MS-based method is developed to increase the likelihood of capturing these modified signaling peptides and to provide improved sequence coverage and accurate glycosite localization, enabling the first large-scale discovery of O-glycosylation on signaling peptides. 28726377 3 36 theme glycosylation 513:525 arg1 occurrence 480:489 the occurrence 476:489 the occurrence of naturally O-linked glycosylation on the signaling peptides extracted from mouse and human pancreatic islets 476:600 Here we explore the occurrence of naturally O-linked glycosylation on the signaling peptides extracted from mouse and human pancreatic islets using mass spectrometry (MS). 28726377 1 37 theme hydroxyl 236:243 arg1 threonine 264:272 threonine 264:272 threonine 264:272 O-Linked glycosylation often involves the covalent attachment of sugar moieties to the hydroxyl group of serine or threonine on proteins/peptides. 28726377 1 37 theme hydroxyl 236:243 arg1 serine 254:259 serine 254:259 serine 254:259 O-Linked glycosylation often involves the covalent attachment of sugar moieties to the hydroxyl group of serine or threonine on proteins/peptides. 28726377 1 37 theme hydroxyl 236:243 arg1 group 245:249 the hydroxyl group 232:249 the hydroxyl group of serine or threonine on proteins/peptides 232:293 O-Linked glycosylation often involves the covalent attachment of sugar moieties to the hydroxyl group of serine or threonine on proteins/peptides. 28726377 6 38 theme potential 1114:1122 arg1 functions 1130:1138 potential novel functions 1114:1138 potential novel functions 1114:1138 This discovery may reveal potential novel functions as glycosylation could influence their conformation and biostability. 28726377 4 39 theme first 844:848 arg1 discovery 862:870 the first large-scale discovery 840:870 the first large-scale discovery of O-glycosylation 840:889 A novel targeted MS-based method is developed to increase the likelihood of capturing these modified signaling peptides and to provide improved sequence coverage and accurate glycosite localization, enabling the first large-scale discovery of O-glycosylation on signaling peptides. 28726377 5 40 theme glycosylated 922:933 arg1 peptides 945:952 Several glycosylated signaling peptides 914:952 Several glycosylated signaling peptides with multiple glycoforms 914:977 Several glycosylated signaling peptides with multiple glycoforms are identified, including the first report of glycosylated insulin-B chain and insulin-C peptide and BigLEN. 28726377 0 41 theme O-Glycosylated 57:70 arg1 Insulin 72:78 O-Glycosylated Insulin 57:78 O-Glycosylated Insulin 57:78 Targeted Mass Spectrometry Approach Enabled Discovery of O-Glycosylated Insulin and Related Signaling Peptides in Mouse and Human Pancreatic Islets. 28726377 7 42 theme important 1370:1378 arg1 insights 1380:1387 important insights 1370:1387 important insights into diabetes research and therapeutic treatments 1370:1437 Given the importance of insulin and its related peptide hormones and previous studies of glycosylated insulin analogues, this natural glycosylation may provide important insights into diabetes research and therapeutic treatments. 28726377 4 43 theme novel 634:638 arg1 method 658:663 A novel targeted MS-based method 632:663 A novel targeted MS-based method 632:663 A novel targeted MS-based method is developed to increase the likelihood of capturing these modified signaling peptides and to provide improved sequence coverage and accurate glycosite localization, enabling the first large-scale discovery of O-glycosylation on signaling peptides. 28726377 4 44 gly glycosite 807:815 arg2 glycosite 807:815 accurate glycosite localization 798:828 accurate glycosite localization 798:828 A novel targeted MS-based method is developed to increase the likelihood of capturing these modified signaling peptides and to provide improved sequence coverage and accurate glycosite localization, enabling the first large-scale discovery of O-glycosylation on signaling peptides. 28726377 2 45 theme glycosylated 377:388 arg1 peptides 400:407 glycosylated signaling peptides 377:407 glycosylated signaling peptides 377:407 Despite growing interest in glycoproteins, little attention has been directed to glycosylated signaling peptides, largely due to lack of enabling analytical tools. 28726377 5 46 theme Several 914:920 arg1 peptides 945:952 Several glycosylated signaling peptides 914:952 Several glycosylated signaling peptides with multiple glycoforms 914:977 Several glycosylated signaling peptides with multiple glycoforms are identified, including the first report of glycosylated insulin-B chain and insulin-C peptide and BigLEN. 28726377 2 47 theme little 339:344 arg1 attention 346:354 little attention 339:354 little attention 339:354 Despite growing interest in glycoproteins, little attention has been directed to glycosylated signaling peptides, largely due to lack of enabling analytical tools. 28726377 5 48 theme signaling 935:943 arg1 peptides 945:952 Several glycosylated signaling peptides 914:952 Several glycosylated signaling peptides with multiple glycoforms 914:977 Several glycosylated signaling peptides with multiple glycoforms are identified, including the first report of glycosylated insulin-B chain and insulin-C peptide and BigLEN. 28726377 0 49 theme Pancreatic 130:139 arg1 Islets 141:146 Pancreatic Islets 130:146 Pancreatic Islets 130:146 Targeted Mass Spectrometry Approach Enabled Discovery of O-Glycosylated Insulin and Related Signaling Peptides in Mouse and Human Pancreatic Islets. 28726377 3 50 theme pancreatic 584:593 arg1 islets 595:600 human pancreatic islets 578:600 human pancreatic islets 578:600 Here we explore the occurrence of naturally O-linked glycosylation on the signaling peptides extracted from mouse and human pancreatic islets using mass spectrometry (MS). 28726377 1 51 theme sugar 214:218 arg1 moieties 220:227 sugar moieties 214:227 sugar moieties 214:227 O-Linked glycosylation often involves the covalent attachment of sugar moieties to the hydroxyl group of serine or threonine on proteins/peptides. 28726377 4 52 theme MS-based 649:656 arg1 method 658:663 A novel targeted MS-based method 632:663 A novel targeted MS-based method 632:663 A novel targeted MS-based method is developed to increase the likelihood of capturing these modified signaling peptides and to provide improved sequence coverage and accurate glycosite localization, enabling the first large-scale discovery of O-glycosylation on signaling peptides. 28726377 7 53 theme analogues 1320:1328 arg1 studies 1288:1294 previous studies 1279:1294 previous studies of glycosylated insulin analogues 1279:1328 Given the importance of insulin and its related peptide hormones and previous studies of glycosylated insulin analogues, this natural glycosylation may provide important insights into diabetes research and therapeutic treatments. 28726377 7 53 theme analogues 1320:1328 arg1 importance 1220:1229 the importance 1216:1229 the importance of insulin and its related peptide hormones 1216:1273 Given the importance of insulin and its related peptide hormones and previous studies of glycosylated insulin analogues, this natural glycosylation may provide important insights into diabetes research and therapeutic treatments. 28726377 3 54 link O-linked 504:511 arg1 glycosylation 513:525 naturally O-linked glycosylation 494:525 naturally O-linked glycosylation 494:525 Here we explore the occurrence of naturally O-linked glycosylation on the signaling peptides extracted from mouse and human pancreatic islets using mass spectrometry (MS). 28726377 4 55 theme signaling 733:741 arg1 peptides 743:750 these modified signaling peptides 718:750 these modified signaling peptides 718:750 A novel targeted MS-based method is developed to increase the likelihood of capturing these modified signaling peptides and to provide improved sequence coverage and accurate glycosite localization, enabling the first large-scale discovery of O-glycosylation on signaling peptides. 28726377 1 56 theme O-Linked 149:156 arg1 glycosylation 158:170 O-Linked glycosylation 149:170 O-Linked glycosylation 149:170 O-Linked glycosylation often involves the covalent attachment of sugar moieties to the hydroxyl group of serine or threonine on proteins/peptides. 28726377 7 57 theme insulin 1312:1318 arg1 analogues 1320:1328 glycosylated insulin analogues 1299:1328 glycosylated insulin analogues 1299:1328 Given the importance of insulin and its related peptide hormones and previous studies of glycosylated insulin analogues, this natural glycosylation may provide important insights into diabetes research and therapeutic treatments. 28726377 0 58 theme Signaling 92:100 arg1 Peptides 102:109 Related Signaling Peptides 84:109 Related Signaling Peptides in Mouse and Human Pancreatic Islets 84:146 Targeted Mass Spectrometry Approach Enabled Discovery of O-Glycosylated Insulin and Related Signaling Peptides in Mouse and Human Pancreatic Islets. 28726377 7 59 theme glycosylated 1299:1310 arg1 analogues 1320:1328 glycosylated insulin analogues 1299:1328 glycosylated insulin analogues 1299:1328 Given the importance of insulin and its related peptide hormones and previous studies of glycosylated insulin analogues, this natural glycosylation may provide important insights into diabetes research and therapeutic treatments. 28726377 5 60 theme insulin-B 1038:1046 arg1 chain 1048:1052 glycosylated insulin-B chain and insulin-C peptide 1025:1074 chain 1048:1052 Several glycosylated signaling peptides with multiple glycoforms are identified, including the first report of glycosylated insulin-B chain and insulin-C peptide and BigLEN. 28726377 5 61 theme chain 1048:1052 arg1 report 1015:1020 the first report 1005:1020 the first report of glycosylated insulin-B chain and insulin-C peptide and BigLEN 1005:1085 Several glycosylated signaling peptides with multiple glycoforms are identified, including the first report of glycosylated insulin-B chain and insulin-C peptide and BigLEN. 28726377 7 62 gly glycosylated 1299:1310 arg1 analogues 1320:1328 glycosylated insulin analogues 1299:1328 glycosylated insulin analogues 1299:1328 Given the importance of insulin and its related peptide hormones and previous studies of glycosylated insulin analogues, this natural glycosylation may provide important insights into diabetes research and therapeutic treatments. 28726377 0 63 from Discovery 44:52 arg1 Human 124:128 Human 124:128 Human 124:128 Targeted Mass Spectrometry Approach Enabled Discovery of O-Glycosylated Insulin and Related Signaling Peptides in Mouse and Human Pancreatic Islets. 28726377 0 63 from Discovery 44:52 arg1 Mouse 114:118 Mouse 114:118 Mouse 114:118 Targeted Mass Spectrometry Approach Enabled Discovery of O-Glycosylated Insulin and Related Signaling Peptides in Mouse and Human Pancreatic Islets. 28726377 4 64 theme glycosite 807:815 arg1 localization 817:828 accurate glycosite localization 798:828 accurate glycosite localization 798:828 A novel targeted MS-based method is developed to increase the likelihood of capturing these modified signaling peptides and to provide improved sequence coverage and accurate glycosite localization, enabling the first large-scale discovery of O-glycosylation on signaling peptides. 28726377 2 65 theme due 418:420 arg1 peptides 400:407 glycosylated signaling peptides 377:407 glycosylated signaling peptides 377:407 Despite growing interest in glycoproteins, little attention has been directed to glycosylated signaling peptides, largely due to lack of enabling analytical tools. 28726377 0 66 theme Mass 9:12 arg1 Approach 27:34 Targeted Mass Spectrometry Approach 0:34 Targeted Mass Spectrometry Approach 0:34 Targeted Mass Spectrometry Approach Enabled Discovery of O-Glycosylated Insulin and Related Signaling Peptides in Mouse and Human Pancreatic Islets. 28726377 5 67 theme first 1009:1013 arg1 report 1015:1020 the first report 1005:1020 the first report of glycosylated insulin-B chain and insulin-C peptide and BigLEN 1005:1085 Several glycosylated signaling peptides with multiple glycoforms are identified, including the first report of glycosylated insulin-B chain and insulin-C peptide and BigLEN. 28726377 7 68 theme peptide 1258:1264 arg1 hormones 1266:1273 its related peptide hormones 1246:1273 its related peptide hormones 1246:1273 Given the importance of insulin and its related peptide hormones and previous studies of glycosylated insulin analogues, this natural glycosylation may provide important insights into diabetes research and therapeutic treatments. 28726377 2 69 theme tools 453:457 arg1 lack 425:428 lack 425:428 lack of enabling analytical tools 425:457 Despite growing interest in glycoproteins, little attention has been directed to glycosylated signaling peptides, largely due to lack of enabling analytical tools. 28726377 4 70 theme sequence 776:783 arg1 coverage 785:792 improved sequence coverage 767:792 improved sequence coverage 767:792 A novel targeted MS-based method is developed to increase the likelihood of capturing these modified signaling peptides and to provide improved sequence coverage and accurate glycosite localization, enabling the first large-scale discovery of O-glycosylation on signaling peptides. 28726377 2 71 theme enabling 433:440 arg1 tools 453:457 enabling analytical tools 433:457 enabling analytical tools 433:457 Despite growing interest in glycoproteins, little attention has been directed to glycosylated signaling peptides, largely due to lack of enabling analytical tools. 28726377 6 72 theme novel 1124:1128 arg1 functions 1130:1138 potential novel functions 1114:1138 potential novel functions 1114:1138 This discovery may reveal potential novel functions as glycosylation could influence their conformation and biostability. 28726377 2 73 gly glycosylated 377:388 arg1 peptides 400:407 glycosylated signaling peptides 377:407 glycosylated signaling peptides 377:407 Despite growing interest in glycoproteins, little attention has been directed to glycosylated signaling peptides, largely due to lack of enabling analytical tools. 28726377 4 74 theme large-scale 850:860 arg1 discovery 862:870 the first large-scale discovery 840:870 the first large-scale discovery of O-glycosylation 840:889 A novel targeted MS-based method is developed to increase the likelihood of capturing these modified signaling peptides and to provide improved sequence coverage and accurate glycosite localization, enabling the first large-scale discovery of O-glycosylation on signaling peptides. 28726377 7 75 theme insulin 1234:1240 arg1 studies 1288:1294 previous studies 1279:1294 previous studies of glycosylated insulin analogues 1279:1328 Given the importance of insulin and its related peptide hormones and previous studies of glycosylated insulin analogues, this natural glycosylation may provide important insights into diabetes research and therapeutic treatments. 28726377 7 75 theme insulin 1234:1240 arg1 importance 1220:1229 the importance 1216:1229 the importance of insulin and its related peptide hormones 1216:1273 Given the importance of insulin and its related peptide hormones and previous studies of glycosylated insulin analogues, this natural glycosylation may provide important insights into diabetes research and therapeutic treatments. 28726377 7 76 theme diabetes 1394:1401 arg1 research 1403:1410 diabetes research 1394:1410 diabetes research 1394:1410 Given the importance of insulin and its related peptide hormones and previous studies of glycosylated insulin analogues, this natural glycosylation may provide important insights into diabetes research and therapeutic treatments. 28726377 5 77 with peptides 945:952 arg1 glycoforms 968:977 multiple glycoforms 959:977 multiple glycoforms 959:977 Several glycosylated signaling peptides with multiple glycoforms are identified, including the first report of glycosylated insulin-B chain and insulin-C peptide and BigLEN. 28726377 3 78 from occurrence 480:489 arg1 peptides 544:551 the signaling peptides 530:551 the signaling peptides extracted from mouse and human pancreatic islets 530:600 Here we explore the occurrence of naturally O-linked glycosylation on the signaling peptides extracted from mouse and human pancreatic islets using mass spectrometry (MS). 28726377 5 79 theme peptide 1068:1074 arg1 report 1015:1020 the first report 1005:1020 the first report of glycosylated insulin-B chain and insulin-C peptide and BigLEN 1005:1085 Several glycosylated signaling peptides with multiple glycoforms are identified, including the first report of glycosylated insulin-B chain and insulin-C peptide and BigLEN. 28726377 3 80 theme O-linked 504:511 arg1 glycosylation 513:525 naturally O-linked glycosylation 494:525 naturally O-linked glycosylation 494:525 Here we explore the occurrence of naturally O-linked glycosylation on the signaling peptides extracted from mouse and human pancreatic islets using mass spectrometry (MS). 28726377 5 81 theme BigLEN 1080:1085 arg1 report 1015:1020 the first report 1005:1020 the first report of glycosylated insulin-B chain and insulin-C peptide and BigLEN 1005:1085 Several glycosylated signaling peptides with multiple glycoforms are identified, including the first report of glycosylated insulin-B chain and insulin-C peptide and BigLEN. 28726377 4 82 theme targeted 640:647 arg1 method 658:663 A novel targeted MS-based method 632:663 A novel targeted MS-based method 632:663 A novel targeted MS-based method is developed to increase the likelihood of capturing these modified signaling peptides and to provide improved sequence coverage and accurate glycosite localization, enabling the first large-scale discovery of O-glycosylation on signaling peptides. 28726377 0 83 from Human 124:128 arg1 Discovery 44:52 Discovery 44:52 Discovery of O-Glycosylated Insulin and Related Signaling Peptides in Mouse and Human Pancreatic Islets 44:146 Targeted Mass Spectrometry Approach Enabled Discovery of O-Glycosylated Insulin and Related Signaling Peptides in Mouse and Human Pancreatic Islets. 28726377 2 84 theme signaling 390:398 arg1 peptides 400:407 glycosylated signaling peptides 377:407 glycosylated signaling peptides 377:407 Despite growing interest in glycoproteins, little attention has been directed to glycosylated signaling peptides, largely due to lack of enabling analytical tools. 28726377 1 85 theme serine 254:259 arg1 threonine 264:272 threonine 264:272 threonine 264:272 O-Linked glycosylation often involves the covalent attachment of sugar moieties to the hydroxyl group of serine or threonine on proteins/peptides. 28726377 1 85 theme serine 254:259 arg1 serine 254:259 serine 254:259 serine 254:259 O-Linked glycosylation often involves the covalent attachment of sugar moieties to the hydroxyl group of serine or threonine on proteins/peptides. 28726377 1 85 theme serine 254:259 arg1 group 245:249 the hydroxyl group 232:249 the hydroxyl group of serine or threonine on proteins/peptides 232:293 O-Linked glycosylation often involves the covalent attachment of sugar moieties to the hydroxyl group of serine or threonine on proteins/peptides. 28228555 0 0 theme Sclerosis 93:101 arg1 Pathogenesis 68:79 Pathogenesis 68:79 Pathogenesis of Multiple Sclerosis 68:101 MicroRNA-15b Suppresses Th17 Differentiation and Is Associated with Pathogenesis of Multiple Sclerosis by Targeting O-GlcNAc Transferase. 28228555 7 1 theme miR-15b 1214:1220 arg1 pathogenesis 1254:1265 the pathogenesis 1250:1265 the pathogenesis of MS 1250:1271 These results contribute to the importance of miR-15b in Th17 differentiation and the pathogenesis of MS. 28228555 7 1 theme miR-15b 1214:1220 arg1 importance 1200:1209 the importance 1196:1209 the importance of miR-15b in Th17 differentiation 1196:1244 These results contribute to the importance of miR-15b in Th17 differentiation and the pathogenesis of MS. 28228555 2 2 from involvement 310:320 arg1 development 350:360 the development 346:360 the development of MS 346:366 Although the involvement of certain microRNAs in the development of MS has been reported, their role in Th17-driven autoimmunity is still poorly understood. 28228555 1 3 theme multiple 272:279 arg1 sclerosis 281:289 multiple sclerosis 272:289 multiple sclerosis (MS) 272:294 IL-17-producing Th17 cells have gradually become considered as key factors in the pathogenesis of many autoimmune diseases, including multiple sclerosis (MS). 28228555 1 3 theme multiple 272:279 arg1 MS 292:293 MS 292:293 MS 292:293 IL-17-producing Th17 cells have gradually become considered as key factors in the pathogenesis of many autoimmune diseases, including multiple sclerosis (MS). 28228555 0 4 theme Multiple 84:91 arg1 Sclerosis 93:101 Multiple Sclerosis 84:101 Multiple Sclerosis 84:101 MicroRNA-15b Suppresses Th17 Differentiation and Is Associated with Pathogenesis of Multiple Sclerosis by Targeting O-GlcNAc Transferase. 28228555 2 5 theme MS 365:366 arg1 development 350:360 the development 346:360 the development of MS 346:366 Although the involvement of certain microRNAs in the development of MS has been reported, their role in Th17-driven autoimmunity is still poorly understood. 28228555 4 6 theme miR-15b 805:811 arg1 knockdown 792:800 knockdown 792:800 knockdown of miR-15b 792:811 Overexpression of miR-15b alleviated experimental autoimmune encephalomyelitis, whereas knockdown of miR-15b aggravated it. 28228555 6 7 theme transcriptional 1036:1050 arg1 regulation 1052:1061 the transcriptional regulation 1032:1061 the transcriptional regulation of retinoic acid-related orphan receptor γT through O-linked N-acetylglucosamine glycosylation of NF-κB 1032:1165 We also found that O-linked N-acetylglucosamine transferase is a potential target of miR-15b, enabling it to affect the transcriptional regulation of retinoic acid-related orphan receptor γT through O-linked N-acetylglucosamine glycosylation of NF-κB. 28228555 6 8 theme O-linked N-acetylglucosamine 935:962 arg1 target 991:996 a potential target 979:996 a potential target of miR-15b 979:1007 We also found that O-linked N-acetylglucosamine transferase is a potential target of miR-15b, enabling it to affect the transcriptional regulation of retinoic acid-related orphan receptor γT through O-linked N-acetylglucosamine glycosylation of NF-κB. 28228555 6 8 theme O-linked N-acetylglucosamine 935:962 arg1 transferase 964:974 O-linked N-acetylglucosamine transferase 935:974 O-linked N-acetylglucosamine transferase 935:974 We also found that O-linked N-acetylglucosamine transferase is a potential target of miR-15b, enabling it to affect the transcriptional regulation of retinoic acid-related orphan receptor γT through O-linked N-acetylglucosamine glycosylation of NF-κB. 28228555 3 9 theme Th17-associated 528:542 arg1 effects 544:550 Th17-associated effects 528:550 Th17-associated effects 528:550 In this study, we identified microRNA (miR)-15b as an important factor in Th17-associated effects and determined that the expression of miR-15b is significantly downregulated in MS patients and in mice with experimental autoimmune encephalomyelitis. 28228555 3 10 with mice 651:654 arg1 encephalomyelitis 685:701 experimental autoimmune encephalomyelitis 661:701 experimental autoimmune encephalomyelitis 661:701 In this study, we identified microRNA (miR)-15b as an important factor in Th17-associated effects and determined that the expression of miR-15b is significantly downregulated in MS patients and in mice with experimental autoimmune encephalomyelitis. 28228555 4 11 theme experimental 741:752 arg1 encephalomyelitis 765:781 experimental autoimmune encephalomyelitis 741:781 experimental autoimmune encephalomyelitis 741:781 Overexpression of miR-15b alleviated experimental autoimmune encephalomyelitis, whereas knockdown of miR-15b aggravated it. 28228555 3 12 from factor 518:523 arg1 effects 544:550 Th17-associated effects 528:550 Th17-associated effects 528:550 In this study, we identified microRNA (miR)-15b as an important factor in Th17-associated effects and determined that the expression of miR-15b is significantly downregulated in MS patients and in mice with experimental autoimmune encephalomyelitis. 28228555 3 13 theme important 508:516 arg1 -15b 497:500 microRNA (miR)-15b 483:500 microRNA (miR)-15b 483:500 In this study, we identified microRNA (miR)-15b as an important factor in Th17-associated effects and determined that the expression of miR-15b is significantly downregulated in MS patients and in mice with experimental autoimmune encephalomyelitis. 28228555 3 13 theme important 508:516 arg1 factor 518:523 an important factor 505:523 an important factor in Th17-associated effects 505:550 In this study, we identified microRNA (miR)-15b as an important factor in Th17-associated effects and determined that the expression of miR-15b is significantly downregulated in MS patients and in mice with experimental autoimmune encephalomyelitis. 28228555 0 14 theme O-GlcNAc 116:123 arg1 Transferase 125:135 O-GlcNAc Transferase 116:135 O-GlcNAc Transferase 116:135 MicroRNA-15b Suppresses Th17 Differentiation and Is Associated with Pathogenesis of Multiple Sclerosis by Targeting O-GlcNAc Transferase. 28228555 6 15 theme orphan 1088:1093 arg1 receptor 1095:1102 retinoic acid-related orphan receptor 1066:1102 retinoic acid-related orphan receptor γT through O-linked N-acetylglucosamine glycosylation of NF-κB 1066:1165 We also found that O-linked N-acetylglucosamine transferase is a potential target of miR-15b, enabling it to affect the transcriptional regulation of retinoic acid-related orphan receptor γT through O-linked N-acetylglucosamine glycosylation of NF-κB. 28228555 1 16 theme key 201:203 arg1 factors 205:211 key factors 201:211 key factors 201:211 IL-17-producing Th17 cells have gradually become considered as key factors in the pathogenesis of many autoimmune diseases, including multiple sclerosis (MS). 28228555 1 16 theme key 201:203 arg1 sclerosis 281:289 multiple sclerosis 272:289 multiple sclerosis (MS) 272:294 IL-17-producing Th17 cells have gradually become considered as key factors in the pathogenesis of many autoimmune diseases, including multiple sclerosis (MS). 28228555 7 17 theme MS 1270:1271 arg1 pathogenesis 1254:1265 the pathogenesis 1250:1265 the pathogenesis of MS 1250:1271 These results contribute to the importance of miR-15b in Th17 differentiation and the pathogenesis of MS. 28228555 7 17 theme MS 1270:1271 arg1 importance 1200:1209 the importance 1196:1209 the importance of miR-15b in Th17 differentiation 1196:1244 These results contribute to the importance of miR-15b in Th17 differentiation and the pathogenesis of MS. 28228555 2 18 theme microRNAs 333:341 arg1 involvement 310:320 the involvement 306:320 the involvement of certain microRNAs in the development of MS 306:366 Although the involvement of certain microRNAs in the development of MS has been reported, their role in Th17-driven autoimmunity is still poorly understood. 28228555 6 19 theme NF-κB 1161:1165 arg1 glycosylation 1144:1156 O-linked N-acetylglucosamine glycosylation 1115:1156 O-linked N-acetylglucosamine glycosylation of NF-κB 1115:1165 We also found that O-linked N-acetylglucosamine transferase is a potential target of miR-15b, enabling it to affect the transcriptional regulation of retinoic acid-related orphan receptor γT through O-linked N-acetylglucosamine glycosylation of NF-κB. 28228555 2 20 theme certain 325:331 arg1 microRNAs 333:341 certain microRNAs 325:341 certain microRNAs 325:341 Although the involvement of certain microRNAs in the development of MS has been reported, their role in Th17-driven autoimmunity is still poorly understood. 28228555 7 21 from pathogenesis 1254:1265 arg1 differentiation 1230:1244 Th17 differentiation 1225:1244 Th17 differentiation 1225:1244 These results contribute to the importance of miR-15b in Th17 differentiation and the pathogenesis of MS. 28228555 5 22 theme Th17 868:871 arg1 differentiation 873:887 Th17 differentiation 868:887 Th17 differentiation 868:887 We demonstrated that miR-15b suppressed Th17 differentiation both in vivo and in vitro. 28228555 0 23 theme Th17 24:27 arg1 Differentiation 29:43 Th17 Differentiation 24:43 Th17 Differentiation 24:43 MicroRNA-15b Suppresses Th17 Differentiation and Is Associated with Pathogenesis of Multiple Sclerosis by Targeting O-GlcNAc Transferase. 28228555 6 24 gly glycosylation 1144:1156 arg1 NF-κB 1161:1165 NF-κB 1161:1165 NF-κB 1161:1165 We also found that O-linked N-acetylglucosamine transferase is a potential target of miR-15b, enabling it to affect the transcriptional regulation of retinoic acid-related orphan receptor γT through O-linked N-acetylglucosamine glycosylation of NF-κB. 28228555 6 25 theme O-linked N-acetylglucosamine 1115:1142 arg1 glycosylation 1144:1156 O-linked N-acetylglucosamine glycosylation 1115:1156 O-linked N-acetylglucosamine glycosylation of NF-κB 1115:1165 We also found that O-linked N-acetylglucosamine transferase is a potential target of miR-15b, enabling it to affect the transcriptional regulation of retinoic acid-related orphan receptor γT through O-linked N-acetylglucosamine glycosylation of NF-κB. 28228555 3 26 theme miR 493:495 arg1 -15b 497:500 microRNA (miR)-15b 483:500 microRNA (miR)-15b 483:500 In this study, we identified microRNA (miR)-15b as an important factor in Th17-associated effects and determined that the expression of miR-15b is significantly downregulated in MS patients and in mice with experimental autoimmune encephalomyelitis. 28228555 3 26 theme miR 493:495 arg1 factor 518:523 an important factor 505:523 an important factor in Th17-associated effects 505:550 In this study, we identified microRNA (miR)-15b as an important factor in Th17-associated effects and determined that the expression of miR-15b is significantly downregulated in MS patients and in mice with experimental autoimmune encephalomyelitis. 28228555 7 27 from importance 1200:1209 arg1 differentiation 1230:1244 Th17 differentiation 1225:1244 Th17 differentiation 1225:1244 These results contribute to the importance of miR-15b in Th17 differentiation and the pathogenesis of MS. 28228555 3 28 theme MS 632:633 arg1 patients 635:642 MS patients 632:642 MS patients 632:642 In this study, we identified microRNA (miR)-15b as an important factor in Th17-associated effects and determined that the expression of miR-15b is significantly downregulated in MS patients and in mice with experimental autoimmune encephalomyelitis. 28228555 3 29 theme miR-15b 590:596 arg1 expression 576:585 the expression 572:585 the expression of miR-15b 572:596 In this study, we identified microRNA (miR)-15b as an important factor in Th17-associated effects and determined that the expression of miR-15b is significantly downregulated in MS patients and in mice with experimental autoimmune encephalomyelitis. 28228555 1 30 theme many 236:239 arg1 diseases 252:259 many autoimmune diseases 236:259 many autoimmune diseases 236:259 IL-17-producing Th17 cells have gradually become considered as key factors in the pathogenesis of many autoimmune diseases, including multiple sclerosis (MS). 28228555 7 31 theme Th17 1225:1228 arg1 differentiation 1230:1244 Th17 differentiation 1225:1244 Th17 differentiation 1225:1244 These results contribute to the importance of miR-15b in Th17 differentiation and the pathogenesis of MS. 28228555 6 32 theme miR-15b 1001:1007 arg1 target 991:996 a potential target 979:996 a potential target of miR-15b 979:1007 We also found that O-linked N-acetylglucosamine transferase is a potential target of miR-15b, enabling it to affect the transcriptional regulation of retinoic acid-related orphan receptor γT through O-linked N-acetylglucosamine glycosylation of NF-κB. 28228555 6 32 theme miR-15b 1001:1007 arg1 transferase 964:974 O-linked N-acetylglucosamine transferase 935:974 O-linked N-acetylglucosamine transferase 935:974 We also found that O-linked N-acetylglucosamine transferase is a potential target of miR-15b, enabling it to affect the transcriptional regulation of retinoic acid-related orphan receptor γT through O-linked N-acetylglucosamine glycosylation of NF-κB. 28228555 3 33 theme experimental 661:672 arg1 encephalomyelitis 685:701 experimental autoimmune encephalomyelitis 661:701 experimental autoimmune encephalomyelitis 661:701 In this study, we identified microRNA (miR)-15b as an important factor in Th17-associated effects and determined that the expression of miR-15b is significantly downregulated in MS patients and in mice with experimental autoimmune encephalomyelitis. 28228555 1 34 theme IL-17-producing 138:152 arg1 cells 159:163 IL-17-producing Th17 cells 138:163 IL-17-producing Th17 cells 138:163 IL-17-producing Th17 cells have gradually become considered as key factors in the pathogenesis of many autoimmune diseases, including multiple sclerosis (MS). 28228555 3 35 theme autoimmune 674:683 arg1 encephalomyelitis 685:701 experimental autoimmune encephalomyelitis 661:701 experimental autoimmune encephalomyelitis 661:701 In this study, we identified microRNA (miR)-15b as an important factor in Th17-associated effects and determined that the expression of miR-15b is significantly downregulated in MS patients and in mice with experimental autoimmune encephalomyelitis. 28228555 2 36 from role 393:396 arg1 autoimmunity 413:424 Th17-driven autoimmunity 401:424 Th17-driven autoimmunity 401:424 Although the involvement of certain microRNAs in the development of MS has been reported, their role in Th17-driven autoimmunity is still poorly understood. 28228555 1 37 theme Th17 154:157 arg1 cells 159:163 IL-17-producing Th17 cells 138:163 IL-17-producing Th17 cells 138:163 IL-17-producing Th17 cells have gradually become considered as key factors in the pathogenesis of many autoimmune diseases, including multiple sclerosis (MS). 28228555 1 38 theme autoimmune 241:250 arg1 diseases 252:259 many autoimmune diseases 236:259 many autoimmune diseases 236:259 IL-17-producing Th17 cells have gradually become considered as key factors in the pathogenesis of many autoimmune diseases, including multiple sclerosis (MS). 28228555 4 39 theme autoimmune 754:763 arg1 encephalomyelitis 765:781 experimental autoimmune encephalomyelitis 741:781 experimental autoimmune encephalomyelitis 741:781 Overexpression of miR-15b alleviated experimental autoimmune encephalomyelitis, whereas knockdown of miR-15b aggravated it. 28228555 1 40 from factors 205:211 arg1 pathogenesis 220:231 the pathogenesis 216:231 the pathogenesis of many autoimmune diseases 216:259 IL-17-producing Th17 cells have gradually become considered as key factors in the pathogenesis of many autoimmune diseases, including multiple sclerosis (MS). 28228555 3 41 theme microRNA 483:490 arg1 -15b 497:500 microRNA (miR)-15b 483:500 microRNA (miR)-15b 483:500 In this study, we identified microRNA (miR)-15b as an important factor in Th17-associated effects and determined that the expression of miR-15b is significantly downregulated in MS patients and in mice with experimental autoimmune encephalomyelitis. 28228555 3 41 theme microRNA 483:490 arg1 factor 518:523 an important factor 505:523 an important factor in Th17-associated effects 505:550 In this study, we identified microRNA (miR)-15b as an important factor in Th17-associated effects and determined that the expression of miR-15b is significantly downregulated in MS patients and in mice with experimental autoimmune encephalomyelitis. 28228555 1 42 theme diseases 252:259 arg1 pathogenesis 220:231 the pathogenesis 216:231 the pathogenesis of many autoimmune diseases 216:259 IL-17-producing Th17 cells have gradually become considered as key factors in the pathogenesis of many autoimmune diseases, including multiple sclerosis (MS). 28228555 2 43 theme Th17-driven 401:411 arg1 autoimmunity 413:424 Th17-driven autoimmunity 401:424 Th17-driven autoimmunity 401:424 Although the involvement of certain microRNAs in the development of MS has been reported, their role in Th17-driven autoimmunity is still poorly understood. 28228555 6 44 theme acid-related 1075:1086 arg1 receptor 1095:1102 retinoic acid-related orphan receptor 1066:1102 retinoic acid-related orphan receptor γT through O-linked N-acetylglucosamine glycosylation of NF-κB 1066:1165 We also found that O-linked N-acetylglucosamine transferase is a potential target of miR-15b, enabling it to affect the transcriptional regulation of retinoic acid-related orphan receptor γT through O-linked N-acetylglucosamine glycosylation of NF-κB. 28228555 6 45 theme potential 981:989 arg1 target 991:996 a potential target 979:996 a potential target of miR-15b 979:1007 We also found that O-linked N-acetylglucosamine transferase is a potential target of miR-15b, enabling it to affect the transcriptional regulation of retinoic acid-related orphan receptor γT through O-linked N-acetylglucosamine glycosylation of NF-κB. 28228555 6 45 theme potential 981:989 arg1 transferase 964:974 O-linked N-acetylglucosamine transferase 935:974 O-linked N-acetylglucosamine transferase 935:974 We also found that O-linked N-acetylglucosamine transferase is a potential target of miR-15b, enabling it to affect the transcriptional regulation of retinoic acid-related orphan receptor γT through O-linked N-acetylglucosamine glycosylation of NF-κB. 28228555 6 46 theme retinoic 1066:1073 arg1 receptor 1095:1102 retinoic acid-related orphan receptor 1066:1102 retinoic acid-related orphan receptor γT through O-linked N-acetylglucosamine glycosylation of NF-κB 1066:1165 We also found that O-linked N-acetylglucosamine transferase is a potential target of miR-15b, enabling it to affect the transcriptional regulation of retinoic acid-related orphan receptor γT through O-linked N-acetylglucosamine glycosylation of NF-κB. 28228555 6 47 theme receptor 1095:1102 arg1 regulation 1052:1061 the transcriptional regulation 1032:1061 the transcriptional regulation of retinoic acid-related orphan receptor γT through O-linked N-acetylglucosamine glycosylation of NF-κB 1032:1165 We also found that O-linked N-acetylglucosamine transferase is a potential target of miR-15b, enabling it to affect the transcriptional regulation of retinoic acid-related orphan receptor γT through O-linked N-acetylglucosamine glycosylation of NF-κB. 28228555 4 48 theme miR-15b 722:728 arg1 Overexpression 704:717 Overexpression 704:717 Overexpression of miR-15b 704:728 Overexpression of miR-15b alleviated experimental autoimmune encephalomyelitis, whereas knockdown of miR-15b aggravated it. 28402840 6 0 dep binding 918:924 arg1 The 914:916 The 914:916 The 914:916 The binding and internalization of PI-Alexa were decreased on DCs previously incubated with mannan, anti-DC-SIGN and/or anti-MR antibodies. 28402840 7 1 theme PI 1192:1193 arg1 effect 1182:1187 the down-modulatory effect 1162:1187 the down-modulatory effect of PI on these cells 1162:1208 In agreement with this, the incubation of DCs with mannan, anti-DC-SIGN and/or anti-MR antibodies abolished the down-modulatory effect of PI on these cells. 28402840 8 2 dep in 1321:1322 arg1 vitro 1324:1328 vitro 1324:1328 vitro 1324:1328 It was also observed that the blockage of CLRs, DC-SIGN and MR on DCs reverted the inhibitory effect of PI in in vitro T cells proliferation. 28402840 1 3 theme molecular 266:274 arg1 PI 295:296 PI 295:296 PI 295:296 High molecular weight components (PI) from Ascaris suum extract down-modulate the immune response against ovalbumin (OVA). 28402840 1 3 theme molecular 266:274 arg1 components 283:292 High molecular weight components 261:292 High molecular weight components (PI) from Ascaris suum extract 261:323 High molecular weight components (PI) from Ascaris suum extract down-modulate the immune response against ovalbumin (OVA). 28402840 0 4 theme extract 86:92 arg1 oligosaccharides 53:68 N-linked oligosaccharides 44:68 N-linked oligosaccharides of Ascaris suum extract 44:92 High molecular weight components containing N-linked oligosaccharides of Ascaris suum extract inhibit the dendritic cells activation through DC-SIGN and MR. Helminths, as well as their secretory/excretory products, induce a tolerogenic immune microenvironment. 28402840 4 5 from residues 809:816 arg1 PI 821:822 PI 821:822 PI 821:822 Our data showed the presence of glycoconjugates with high mannose- and complex-type N-linked oligosaccharide chains and phosphorylcholine residues on PI. 28402840 4 6 theme phosphorylcholine 791:807 arg1 residues 809:816 phosphorylcholine residues 791:816 phosphorylcholine residues 791:816 Our data showed the presence of glycoconjugates with high mannose- and complex-type N-linked oligosaccharide chains and phosphorylcholine residues on PI. 28402840 8 7 from blockage 1241:1248 arg1 DCs 1277:1279 DCs 1277:1279 DCs 1277:1279 It was also observed that the blockage of CLRs, DC-SIGN and MR on DCs reverted the inhibitory effect of PI in in vitro T cells proliferation. 28402840 0 8 theme secretory/excretory 185:203 arg1 products 205:212 their secretory/excretory products 179:212 their secretory/excretory products 179:212 High molecular weight components containing N-linked oligosaccharides of Ascaris suum extract inhibit the dendritic cells activation through DC-SIGN and MR. Helminths, as well as their secretory/excretory products, induce a tolerogenic immune microenvironment. 28402840 1 9 theme weight 276:281 arg1 PI 295:296 PI 295:296 PI 295:296 High molecular weight components (PI) from Ascaris suum extract down-modulate the immune response against ovalbumin (OVA). 28402840 1 9 theme weight 276:281 arg1 components 283:292 High molecular weight components 261:292 High molecular weight components (PI) from Ascaris suum extract 261:323 High molecular weight components (PI) from Ascaris suum extract down-modulate the immune response against ovalbumin (OVA). 28402840 0 10 theme dendritic 106:114 arg1 cells 116:120 the dendritic cells 102:120 the dendritic cells activation 102:131 High molecular weight components containing N-linked oligosaccharides of Ascaris suum extract inhibit the dendritic cells activation through DC-SIGN and MR. Helminths, as well as their secretory/excretory products, induce a tolerogenic immune microenvironment. 28402840 0 11 theme immune 236:241 arg1 microenvironment 243:258 a tolerogenic immune microenvironment 222:258 a tolerogenic immune microenvironment 222:258 High molecular weight components containing N-linked oligosaccharides of Ascaris suum extract inhibit the dendritic cells activation through DC-SIGN and MR. Helminths, as well as their secretory/excretory products, induce a tolerogenic immune microenvironment. 28402840 8 12 theme MR 1271:1272 arg1 blockage 1241:1248 the blockage 1237:1248 the blockage of CLRs, DC-SIGN and MR on DCs 1237:1279 It was also observed that the blockage of CLRs, DC-SIGN and MR on DCs reverted the inhibitory effect of PI in in vitro T cells proliferation. 28402840 8 13 theme inhibitory 1294:1303 arg1 effect 1305:1310 the inhibitory effect 1290:1310 the inhibitory effect of PI in in vitro T cells proliferation 1290:1350 It was also observed that the blockage of CLRs, DC-SIGN and MR on DCs reverted the inhibitory effect of PI in in vitro T cells proliferation. 28402840 9 14 theme PI 1496:1497 arg1 components 1482:1491 N-glycosylated components 1467:1491 N-glycosylated components of PI 1467:1497 Therefore, our data show the involvement of DC-SIGN and MR in the recognition and consequent modulatory effect of N-glycosylated components of PI on DCs. 28402840 1 15 from extract 317:323 arg1 PI 295:296 PI 295:296 PI 295:296 High molecular weight components (PI) from Ascaris suum extract down-modulate the immune response against ovalbumin (OVA). 28402840 1 15 from extract 317:323 arg1 components 283:292 High molecular weight components 261:292 High molecular weight components (PI) from Ascaris suum extract 261:323 High molecular weight components (PI) from Ascaris suum extract down-modulate the immune response against ovalbumin (OVA). 28402840 0 16 contain containing 33:42 arg2 oligosaccharides 53:68 N-linked oligosaccharides 44:68 N-linked oligosaccharides of Ascaris suum extract 44:92 High molecular weight components containing N-linked oligosaccharides of Ascaris suum extract inhibit the dendritic cells activation through DC-SIGN and MR. Helminths, as well as their secretory/excretory products, induce a tolerogenic immune microenvironment. 28402840 0 16 contain containing 33:42 arg1 components 22:31 High molecular weight components 0:31 High molecular weight components containing N-linked oligosaccharides of Ascaris suum extract 0:92 High molecular weight components containing N-linked oligosaccharides of Ascaris suum extract inhibit the dendritic cells activation through DC-SIGN and MR. Helminths, as well as their secretory/excretory products, induce a tolerogenic immune microenvironment. 28402840 7 17 from effect 1182:1187 arg1 cells 1204:1208 these cells 1198:1208 these cells 1198:1208 In agreement with this, the incubation of DCs with mannan, anti-DC-SIGN and/or anti-MR antibodies abolished the down-modulatory effect of PI on these cells. 28402840 6 18 theme PI-Alexa 949:956 arg1 internalization 930:944 internalization 930:944 internalization 930:944 The binding and internalization of PI-Alexa were decreased on DCs previously incubated with mannan, anti-DC-SIGN and/or anti-MR antibodies. 28402840 6 18 theme PI-Alexa 949:956 arg1 binding 918:924 binding 918:924 binding 918:924 The binding and internalization of PI-Alexa were decreased on DCs previously incubated with mannan, anti-DC-SIGN and/or anti-MR antibodies. 28402840 4 19 from chains 780:785 arg1 PI 821:822 PI 821:822 PI 821:822 Our data showed the presence of glycoconjugates with high mannose- and complex-type N-linked oligosaccharide chains and phosphorylcholine residues on PI. 28402840 4 20 theme oligosaccharide 764:778 arg1 chains 780:785 complex-type N-linked oligosaccharide chains 742:785 complex-type N-linked oligosaccharide chains 742:785 Our data showed the presence of glycoconjugates with high mannose- and complex-type N-linked oligosaccharide chains and phosphorylcholine residues on PI. 28402840 2 21 theme direct 398:403 arg1 effect 405:410 direct effect 398:410 direct effect 398:410 The PI exerts direct effect on dendritic cells (DCs) independent of TLR 2, 4 and MyD88 molecule and, thus, decreases the T lymphocytes response. 28402840 0 22 theme cells 116:120 arg1 activation 122:131 the dendritic cells activation 102:131 the dendritic cells activation 102:131 High molecular weight components containing N-linked oligosaccharides of Ascaris suum extract inhibit the dendritic cells activation through DC-SIGN and MR. Helminths, as well as their secretory/excretory products, induce a tolerogenic immune microenvironment. 28402840 4 23 theme N-linked 755:762 arg1 chains 780:785 complex-type N-linked oligosaccharide chains 742:785 complex-type N-linked oligosaccharide chains 742:785 Our data showed the presence of glycoconjugates with high mannose- and complex-type N-linked oligosaccharide chains and phosphorylcholine residues on PI. 28402840 9 24 theme DC-SIGN 1397:1403 arg1 effect 1457:1462 consequent modulatory effect 1435:1462 consequent modulatory effect of N-glycosylated components of PI on DCs 1435:1504 Therefore, our data show the involvement of DC-SIGN and MR in the recognition and consequent modulatory effect of N-glycosylated components of PI on DCs. 28402840 9 24 theme DC-SIGN 1397:1403 arg1 involvement 1382:1392 the involvement 1378:1392 the involvement of DC-SIGN and MR in the recognition 1378:1429 Therefore, our data show the involvement of DC-SIGN and MR in the recognition and consequent modulatory effect of N-glycosylated components of PI on DCs. 28402840 0 25 theme molecular 5:13 arg1 components 22:31 High molecular weight components 0:31 High molecular weight components containing N-linked oligosaccharides of Ascaris suum extract 0:92 High molecular weight components containing N-linked oligosaccharides of Ascaris suum extract inhibit the dendritic cells activation through DC-SIGN and MR. Helminths, as well as their secretory/excretory products, induce a tolerogenic immune microenvironment. 28402840 7 26 theme down-modulatory 1166:1180 arg1 effect 1182:1187 the down-modulatory effect 1162:1187 the down-modulatory effect of PI on these cells 1162:1208 In agreement with this, the incubation of DCs with mannan, anti-DC-SIGN and/or anti-MR antibodies abolished the down-modulatory effect of PI on these cells. 28402840 0 27 theme tolerogenic 224:234 arg1 microenvironment 243:258 a tolerogenic immune microenvironment 222:258 a tolerogenic immune microenvironment 222:258 High molecular weight components containing N-linked oligosaccharides of Ascaris suum extract inhibit the dendritic cells activation through DC-SIGN and MR. Helminths, as well as their secretory/excretory products, induce a tolerogenic immune microenvironment. 28402840 2 28 theme molecule 471:478 arg1 independent 437:447 independent 437:447 independent 437:447 The PI exerts direct effect on dendritic cells (DCs) independent of TLR 2, 4 and MyD88 molecule and, thus, decreases the T lymphocytes response. 28402840 9 29 theme N-glycosylated 1467:1480 arg1 components 1482:1491 N-glycosylated components 1467:1491 N-glycosylated components of PI 1467:1497 Therefore, our data show the involvement of DC-SIGN and MR in the recognition and consequent modulatory effect of N-glycosylated components of PI on DCs. 28402840 0 30 theme High 0:3 arg1 components 22:31 High molecular weight components 0:31 High molecular weight components containing N-linked oligosaccharides of Ascaris suum extract 0:92 High molecular weight components containing N-linked oligosaccharides of Ascaris suum extract inhibit the dendritic cells activation through DC-SIGN and MR. Helminths, as well as their secretory/excretory products, induce a tolerogenic immune microenvironment. 28402840 3 31 theme activity 661:668 arg1 modulation 643:652 the modulation 639:652 the modulation of DCs activity 639:668 Here, we studied the glycoconjugates in PI and the role of C-type lectin receptors (CLRs), DC-SIGN and MR, in the modulation of DCs activity. 28402840 0 32 link N-linked 44:51 arg1 oligosaccharides 53:68 N-linked oligosaccharides 44:68 N-linked oligosaccharides of Ascaris suum extract 44:92 High molecular weight components containing N-linked oligosaccharides of Ascaris suum extract inhibit the dendritic cells activation through DC-SIGN and MR. Helminths, as well as their secretory/excretory products, induce a tolerogenic immune microenvironment. 28402840 5 33 theme DCs 883:885 arg1 maturation 887:896 the DCs maturation 879:896 the DCs maturation induced by LPS 879:911 In addition, these N-linked glycoconjugates inhibited the DCs maturation induced by LPS. 28402840 2 34 theme lymphocytes 507:517 arg1 response 519:526 the T lymphocytes response 501:526 the T lymphocytes response 501:526 The PI exerts direct effect on dendritic cells (DCs) independent of TLR 2, 4 and MyD88 molecule and, thus, decreases the T lymphocytes response. 28402840 8 35 theme in 1321:1322 arg1 proliferation 1338:1350 in vitro T cells proliferation 1321:1350 in vitro T cells proliferation 1321:1350 It was also observed that the blockage of CLRs, DC-SIGN and MR on DCs reverted the inhibitory effect of PI in in vitro T cells proliferation. 28402840 0 36 theme weight 15:20 arg1 components 22:31 High molecular weight components 0:31 High molecular weight components containing N-linked oligosaccharides of Ascaris suum extract 0:92 High molecular weight components containing N-linked oligosaccharides of Ascaris suum extract inhibit the dendritic cells activation through DC-SIGN and MR. Helminths, as well as their secretory/excretory products, induce a tolerogenic immune microenvironment. 28402840 2 37 theme T 505:505 arg1 lymphocytes 507:517 T lymphocytes 505:517 the T lymphocytes response 501:526 The PI exerts direct effect on dendritic cells (DCs) independent of TLR 2, 4 and MyD88 molecule and, thus, decreases the T lymphocytes response. 28402840 3 38 theme C-type 588:593 arg1 MR 632:633 MR 632:633 MR 632:633 Here, we studied the glycoconjugates in PI and the role of C-type lectin receptors (CLRs), DC-SIGN and MR, in the modulation of DCs activity. 28402840 3 38 theme C-type 588:593 arg1 CLRs 613:616 CLRs 613:616 CLRs 613:616 Here, we studied the glycoconjugates in PI and the role of C-type lectin receptors (CLRs), DC-SIGN and MR, in the modulation of DCs activity. 28402840 3 38 theme C-type 588:593 arg1 DC-SIGN 620:626 DC-SIGN 620:626 DC-SIGN 620:626 Here, we studied the glycoconjugates in PI and the role of C-type lectin receptors (CLRs), DC-SIGN and MR, in the modulation of DCs activity. 28402840 3 38 theme C-type 588:593 arg1 receptors 602:610 C-type lectin receptors 588:610 C-type lectin receptors (CLRs) 588:617 Here, we studied the glycoconjugates in PI and the role of C-type lectin receptors (CLRs), DC-SIGN and MR, in the modulation of DCs activity. 28402840 6 39 theme anti-MR 1034:1040 arg1 antibodies 1042:1051 anti-MR antibodies 1034:1051 anti-MR antibodies 1034:1051 The binding and internalization of PI-Alexa were decreased on DCs previously incubated with mannan, anti-DC-SIGN and/or anti-MR antibodies. 28402840 2 40 theme dendritic 415:423 arg1 DCs 432:434 DCs 432:434 DCs 432:434 The PI exerts direct effect on dendritic cells (DCs) independent of TLR 2, 4 and MyD88 molecule and, thus, decreases the T lymphocytes response. 28402840 2 40 theme dendritic 415:423 arg1 cells 425:429 dendritic cells 415:429 dendritic cells (DCs) independent of TLR 2, 4 and MyD88 molecule 415:478 The PI exerts direct effect on dendritic cells (DCs) independent of TLR 2, 4 and MyD88 molecule and, thus, decreases the T lymphocytes response. 28402840 0 41 theme N-linked 44:51 arg1 oligosaccharides 53:68 N-linked oligosaccharides 44:68 N-linked oligosaccharides of Ascaris suum extract 44:92 High molecular weight components containing N-linked oligosaccharides of Ascaris suum extract inhibit the dendritic cells activation through DC-SIGN and MR. Helminths, as well as their secretory/excretory products, induce a tolerogenic immune microenvironment. 28402840 3 42 theme DCs 657:659 arg1 activity 661:668 DCs activity 657:668 DCs activity 657:668 Here, we studied the glycoconjugates in PI and the role of C-type lectin receptors (CLRs), DC-SIGN and MR, in the modulation of DCs activity. 28402840 0 43 theme MR. 153:155 arg1 Helminths 157:165 MR. Helminths 153:165 MR. Helminths 153:165 High molecular weight components containing N-linked oligosaccharides of Ascaris suum extract inhibit the dendritic cells activation through DC-SIGN and MR. Helminths, as well as their secretory/excretory products, induce a tolerogenic immune microenvironment. 28402840 3 44 theme lectin 595:600 arg1 MR 632:633 MR 632:633 MR 632:633 Here, we studied the glycoconjugates in PI and the role of C-type lectin receptors (CLRs), DC-SIGN and MR, in the modulation of DCs activity. 28402840 3 44 theme lectin 595:600 arg1 CLRs 613:616 CLRs 613:616 CLRs 613:616 Here, we studied the glycoconjugates in PI and the role of C-type lectin receptors (CLRs), DC-SIGN and MR, in the modulation of DCs activity. 28402840 3 44 theme lectin 595:600 arg1 DC-SIGN 620:626 DC-SIGN 620:626 DC-SIGN 620:626 Here, we studied the glycoconjugates in PI and the role of C-type lectin receptors (CLRs), DC-SIGN and MR, in the modulation of DCs activity. 28402840 3 44 theme lectin 595:600 arg1 receptors 602:610 C-type lectin receptors 588:610 C-type lectin receptors (CLRs) 588:617 Here, we studied the glycoconjugates in PI and the role of C-type lectin receptors (CLRs), DC-SIGN and MR, in the modulation of DCs activity. 28402840 8 45 theme PI 1315:1316 arg1 effect 1305:1310 the inhibitory effect 1290:1310 the inhibitory effect of PI in in vitro T cells proliferation 1290:1350 It was also observed that the blockage of CLRs, DC-SIGN and MR on DCs reverted the inhibitory effect of PI in in vitro T cells proliferation. 28402840 3 46 from glycoconjugates 550:564 arg1 PI 569:570 PI 569:570 PI 569:570 Here, we studied the glycoconjugates in PI and the role of C-type lectin receptors (CLRs), DC-SIGN and MR, in the modulation of DCs activity. 28402840 3 46 from glycoconjugates 550:564 arg1 modulation 643:652 the modulation 639:652 the modulation of DCs activity 639:668 Here, we studied the glycoconjugates in PI and the role of C-type lectin receptors (CLRs), DC-SIGN and MR, in the modulation of DCs activity. 28402840 7 47 theme DCs 1096:1098 arg1 incubation 1082:1091 the incubation 1078:1091 the incubation of DCs with mannan, anti-DC-SIGN and/or anti-MR antibodies 1078:1150 In agreement with this, the incubation of DCs with mannan, anti-DC-SIGN and/or anti-MR antibodies abolished the down-modulatory effect of PI on these cells. 28402840 1 48 theme suum 312:315 arg1 extract 317:323 Ascaris suum extract 304:323 Ascaris suum extract 304:323 High molecular weight components (PI) from Ascaris suum extract down-modulate the immune response against ovalbumin (OVA). 28402840 4 49 theme high 724:727 arg1 mannose- 729:736 high mannose- 724:736 high mannose- 724:736 Our data showed the presence of glycoconjugates with high mannose- and complex-type N-linked oligosaccharide chains and phosphorylcholine residues on PI. 28402840 7 50 theme anti-MR 1133:1139 arg1 antibodies 1141:1150 anti-MR antibodies 1133:1150 anti-MR antibodies 1133:1150 In agreement with this, the incubation of DCs with mannan, anti-DC-SIGN and/or anti-MR antibodies abolished the down-modulatory effect of PI on these cells. 28402840 2 51 theme TLR 452:454 arg1 independent 437:447 independent 437:447 independent 437:447 The PI exerts direct effect on dendritic cells (DCs) independent of TLR 2, 4 and MyD88 molecule and, thus, decreases the T lymphocytes response. 28402840 3 52 from role 580:583 arg1 PI 569:570 PI 569:570 PI 569:570 Here, we studied the glycoconjugates in PI and the role of C-type lectin receptors (CLRs), DC-SIGN and MR, in the modulation of DCs activity. 28402840 3 52 from role 580:583 arg1 modulation 643:652 the modulation 639:652 the modulation of DCs activity 639:668 Here, we studied the glycoconjugates in PI and the role of C-type lectin receptors (CLRs), DC-SIGN and MR, in the modulation of DCs activity. 28402840 4 53 theme complex-type 742:753 arg1 chains 780:785 complex-type N-linked oligosaccharide chains 742:785 complex-type N-linked oligosaccharide chains 742:785 Our data showed the presence of glycoconjugates with high mannose- and complex-type N-linked oligosaccharide chains and phosphorylcholine residues on PI. 28402840 9 54 from involvement 1382:1392 arg1 recognition 1419:1429 the recognition 1415:1429 the recognition 1415:1429 Therefore, our data show the involvement of DC-SIGN and MR in the recognition and consequent modulatory effect of N-glycosylated components of PI on DCs. 28402840 9 54 from involvement 1382:1392 arg1 DCs 1502:1504 DCs 1502:1504 DCs 1502:1504 Therefore, our data show the involvement of DC-SIGN and MR in the recognition and consequent modulatory effect of N-glycosylated components of PI on DCs. 28402840 4 55 link N-linked 755:762 arg1 chains 780:785 complex-type N-linked oligosaccharide chains 742:785 complex-type N-linked oligosaccharide chains 742:785 Our data showed the presence of glycoconjugates with high mannose- and complex-type N-linked oligosaccharide chains and phosphorylcholine residues on PI. 28402840 7 56 with incubation 1082:1091 arg1 antibodies 1141:1150 anti-MR antibodies 1133:1150 anti-MR antibodies 1133:1150 In agreement with this, the incubation of DCs with mannan, anti-DC-SIGN and/or anti-MR antibodies abolished the down-modulatory effect of PI on these cells. 28402840 7 56 with incubation 1082:1091 arg1 mannan 1105:1110 mannan 1105:1110 mannan 1105:1110 In agreement with this, the incubation of DCs with mannan, anti-DC-SIGN and/or anti-MR antibodies abolished the down-modulatory effect of PI on these cells. 28402840 7 56 with incubation 1082:1091 arg1 anti-DC-SIGN 1113:1124 anti-DC-SIGN 1113:1124 anti-DC-SIGN 1113:1124 In agreement with this, the incubation of DCs with mannan, anti-DC-SIGN and/or anti-MR antibodies abolished the down-modulatory effect of PI on these cells. 28402840 9 57 theme consequent 1435:1444 arg1 effect 1457:1462 consequent modulatory effect 1435:1462 consequent modulatory effect of N-glycosylated components of PI on DCs 1435:1504 Therefore, our data show the involvement of DC-SIGN and MR in the recognition and consequent modulatory effect of N-glycosylated components of PI on DCs. 28402840 8 58 theme cells 1332:1336 arg1 proliferation 1338:1350 in vitro T cells proliferation 1321:1350 in vitro T cells proliferation 1321:1350 It was also observed that the blockage of CLRs, DC-SIGN and MR on DCs reverted the inhibitory effect of PI in in vitro T cells proliferation. 28402840 4 59 from mannose- 729:736 arg1 PI 821:822 PI 821:822 PI 821:822 Our data showed the presence of glycoconjugates with high mannose- and complex-type N-linked oligosaccharide chains and phosphorylcholine residues on PI. 28402840 5 60 theme N-linked 844:851 arg1 glycoconjugates 853:867 these N-linked glycoconjugates 838:867 these N-linked glycoconjugates 838:867 In addition, these N-linked glycoconjugates inhibited the DCs maturation induced by LPS. 28402840 9 61 gly N-glycosylated 1467:1480 arg1 components 1482:1491 N-glycosylated components 1467:1491 N-glycosylated components of PI 1467:1497 Therefore, our data show the involvement of DC-SIGN and MR in the recognition and consequent modulatory effect of N-glycosylated components of PI on DCs. 28402840 4 62 theme glycoconjugates 703:717 arg1 presence 691:698 the presence 687:698 the presence of glycoconjugates 687:717 Our data showed the presence of glycoconjugates with high mannose- and complex-type N-linked oligosaccharide chains and phosphorylcholine residues on PI. 28402840 8 63 theme T 1330:1330 arg1 proliferation 1338:1350 in vitro T cells proliferation 1321:1350 in vitro T cells proliferation 1321:1350 It was also observed that the blockage of CLRs, DC-SIGN and MR on DCs reverted the inhibitory effect of PI in in vitro T cells proliferation. 28402840 9 64 theme components 1482:1491 arg1 effect 1457:1462 consequent modulatory effect 1435:1462 consequent modulatory effect of N-glycosylated components of PI on DCs 1435:1504 Therefore, our data show the involvement of DC-SIGN and MR in the recognition and consequent modulatory effect of N-glycosylated components of PI on DCs. 28402840 9 64 theme components 1482:1491 arg1 involvement 1382:1392 the involvement 1378:1392 the involvement of DC-SIGN and MR in the recognition 1378:1429 Therefore, our data show the involvement of DC-SIGN and MR in the recognition and consequent modulatory effect of N-glycosylated components of PI on DCs. 28402840 5 65 link N-linked 844:851 arg1 glycoconjugates 853:867 these N-linked glycoconjugates 838:867 these N-linked glycoconjugates 838:867 In addition, these N-linked glycoconjugates inhibited the DCs maturation induced by LPS. 28402840 3 66 theme receptors 602:610 arg1 role 580:583 the role 576:583 the role of C-type lectin receptors (CLRs), DC-SIGN and MR, in the modulation of DCs activity 576:668 Here, we studied the glycoconjugates in PI and the role of C-type lectin receptors (CLRs), DC-SIGN and MR, in the modulation of DCs activity. 28402840 3 66 theme receptors 602:610 arg1 glycoconjugates 550:564 the glycoconjugates 546:564 the glycoconjugates in PI 546:570 Here, we studied the glycoconjugates in PI and the role of C-type lectin receptors (CLRs), DC-SIGN and MR, in the modulation of DCs activity. 28402840 8 67 theme CLRs 1253:1256 arg1 blockage 1241:1248 the blockage 1237:1248 the blockage of CLRs, DC-SIGN and MR on DCs 1237:1279 It was also observed that the blockage of CLRs, DC-SIGN and MR on DCs reverted the inhibitory effect of PI in in vitro T cells proliferation. 28402840 9 68 theme MR 1409:1410 arg1 effect 1457:1462 consequent modulatory effect 1435:1462 consequent modulatory effect of N-glycosylated components of PI on DCs 1435:1504 Therefore, our data show the involvement of DC-SIGN and MR in the recognition and consequent modulatory effect of N-glycosylated components of PI on DCs. 28402840 9 68 theme MR 1409:1410 arg1 involvement 1382:1392 the involvement 1378:1392 the involvement of DC-SIGN and MR in the recognition 1378:1429 Therefore, our data show the involvement of DC-SIGN and MR in the recognition and consequent modulatory effect of N-glycosylated components of PI on DCs. 28402840 8 69 theme DC-SIGN 1259:1265 arg1 blockage 1241:1248 the blockage 1237:1248 the blockage of CLRs, DC-SIGN and MR on DCs 1237:1279 It was also observed that the blockage of CLRs, DC-SIGN and MR on DCs reverted the inhibitory effect of PI in in vitro T cells proliferation. 28402840 0 70 theme suum 81:84 arg1 extract 86:92 Ascaris suum extract 73:92 Ascaris suum extract 73:92 High molecular weight components containing N-linked oligosaccharides of Ascaris suum extract inhibit the dendritic cells activation through DC-SIGN and MR. Helminths, as well as their secretory/excretory products, induce a tolerogenic immune microenvironment. 28402840 9 71 from effect 1457:1462 arg1 recognition 1419:1429 the recognition 1415:1429 the recognition 1415:1429 Therefore, our data show the involvement of DC-SIGN and MR in the recognition and consequent modulatory effect of N-glycosylated components of PI on DCs. 28402840 9 71 from effect 1457:1462 arg1 DCs 1502:1504 DCs 1502:1504 DCs 1502:1504 Therefore, our data show the involvement of DC-SIGN and MR in the recognition and consequent modulatory effect of N-glycosylated components of PI on DCs. 28402840 7 72 with agreement 1057:1065 arg1 this 1072:1075 this 1072:1075 this 1072:1075 In agreement with this, the incubation of DCs with mannan, anti-DC-SIGN and/or anti-MR antibodies abolished the down-modulatory effect of PI on these cells. 28402840 9 73 theme modulatory 1446:1455 arg1 effect 1457:1462 consequent modulatory effect 1435:1462 consequent modulatory effect of N-glycosylated components of PI on DCs 1435:1504 Therefore, our data show the involvement of DC-SIGN and MR in the recognition and consequent modulatory effect of N-glycosylated components of PI on DCs. 28402840 2 74 theme MyD88 465:469 arg1 molecule 471:478 MyD88 molecule 465:478 MyD88 molecule 465:478 The PI exerts direct effect on dendritic cells (DCs) independent of TLR 2, 4 and MyD88 molecule and, thus, decreases the T lymphocytes response. 28402840 1 75 theme immune 343:348 arg1 response 350:357 the immune response 339:357 the immune response against ovalbumin (OVA) 339:381 High molecular weight components (PI) from Ascaris suum extract down-modulate the immune response against ovalbumin (OVA). 28402840 2 76 dep exerts 391:396 arg1 decreases 491:499 decreases 491:499 decreases the T lymphocytes response 491:526 The PI exerts direct effect on dendritic cells (DCs) independent of TLR 2, 4 and MyD88 molecule and, thus, decreases the T lymphocytes response. 28402840 2 77 theme independent 437:447 arg1 DCs 432:434 DCs 432:434 DCs 432:434 The PI exerts direct effect on dendritic cells (DCs) independent of TLR 2, 4 and MyD88 molecule and, thus, decreases the T lymphocytes response. 28402840 2 77 theme independent 437:447 arg1 cells 425:429 dendritic cells 415:429 dendritic cells (DCs) independent of TLR 2, 4 and MyD88 molecule 415:478 The PI exerts direct effect on dendritic cells (DCs) independent of TLR 2, 4 and MyD88 molecule and, thus, decreases the T lymphocytes response. 28402840 8 78 from effect 1305:1310 arg1 proliferation 1338:1350 in vitro T cells proliferation 1321:1350 in vitro T cells proliferation 1321:1350 It was also observed that the blockage of CLRs, DC-SIGN and MR on DCs reverted the inhibitory effect of PI in in vitro T cells proliferation. 28402840 1 79 theme High 261:264 arg1 PI 295:296 PI 295:296 PI 295:296 High molecular weight components (PI) from Ascaris suum extract down-modulate the immune response against ovalbumin (OVA). 28402840 1 79 theme High 261:264 arg1 components 283:292 High molecular weight components 261:292 High molecular weight components (PI) from Ascaris suum extract 261:323 High molecular weight components (PI) from Ascaris suum extract down-modulate the immune response against ovalbumin (OVA). 25660114 5 0 theme cell 1072:1075 arg1 wall 1077:1080 the corn cell wall 1063:1080 the corn cell wall 1063:1080 In addition, both corn grains and corresponding DDGS had similar profiles of individual DFAs and TriFAs, indicating that ferulic acid cross-links in the corn cell wall are presumably not modified during fermentation and DDGS processing. 25660114 2 1 theme TriFAs 570:575 arg1 composition 546:556 composition 546:556 composition of DFAs and TriFAs 546:575 Corn, wheat, and mixed-cereal distiller's dried grains with solubles (DDGS) were investigated for composition of DFAs and TriFAs by reversed phase high-performance liquid chromatography with ultraviolet detection. 25660114 0 2 theme grains 74:79 arg1 dehydrodimer 13:24 Ferulic acid dehydrodimer 0:24 Ferulic acid dehydrodimer 0:24 Ferulic acid dehydrodimer and dehydrotrimer profiles of distiller's dried grains with solubles from different cereal species. 25660114 0 2 theme grains 74:79 arg1 profiles 44:51 dehydrotrimer profiles 30:51 dehydrotrimer profiles 30:51 Ferulic acid dehydrodimer and dehydrotrimer profiles of distiller's dried grains with solubles from different cereal species. 25660114 2 3 theme ultraviolet 639:649 arg1 detection 651:659 ultraviolet detection 639:659 ultraviolet detection 639:659 Corn, wheat, and mixed-cereal distiller's dried grains with solubles (DDGS) were investigated for composition of DFAs and TriFAs by reversed phase high-performance liquid chromatography with ultraviolet detection. 25660114 5 4 theme ferulic 1035:1041 arg1 cross-links 1048:1058 ferulic acid cross-links 1035:1058 ferulic acid cross-links in the corn cell wall 1035:1080 In addition, both corn grains and corresponding DDGS had similar profiles of individual DFAs and TriFAs, indicating that ferulic acid cross-links in the corn cell wall are presumably not modified during fermentation and DDGS processing. 25660114 2 5 theme DFAs 561:564 arg1 composition 546:556 composition 546:556 composition of DFAs and TriFAs 546:575 Corn, wheat, and mixed-cereal distiller's dried grains with solubles (DDGS) were investigated for composition of DFAs and TriFAs by reversed phase high-performance liquid chromatography with ultraviolet detection. 25660114 1 6 theme plant 431:435 arg1 wall 442:445 the plant cell wall 427:445 the plant cell wall 427:445 Ferulic acid dehydrodimers (DFA) and dehydrotrimers (TriFA) ester-linked to plant cell wall polymers may cross-link not only cell wall polysaccharides but also other cell wall components including proteins and lignin, thus enhancing the rigidity and potentially affecting the enzymatic degradation of the plant cell wall. 25660114 5 7 theme acid 1043:1046 arg1 cross-links 1048:1058 ferulic acid cross-links 1035:1058 ferulic acid cross-links in the corn cell wall 1035:1080 In addition, both corn grains and corresponding DDGS had similar profiles of individual DFAs and TriFAs, indicating that ferulic acid cross-links in the corn cell wall are presumably not modified during fermentation and DDGS processing. 25660114 1 8 link ester-linked 186:197 arg1 DFA 154:156 DFA 154:156 DFA 154:156 Ferulic acid dehydrodimers (DFA) and dehydrotrimers (TriFA) ester-linked to plant cell wall polymers may cross-link not only cell wall polysaccharides but also other cell wall components including proteins and lignin, thus enhancing the rigidity and potentially affecting the enzymatic degradation of the plant cell wall. 25660114 1 8 link ester-linked 186:197 arg1 dehydrodimers 139:151 Ferulic acid dehydrodimers 126:151 Ferulic acid dehydrodimers (DFA) 126:157 Ferulic acid dehydrodimers (DFA) and dehydrotrimers (TriFA) ester-linked to plant cell wall polymers may cross-link not only cell wall polysaccharides but also other cell wall components including proteins and lignin, thus enhancing the rigidity and potentially affecting the enzymatic degradation of the plant cell wall. 25660114 1 9 theme cell 437:440 arg1 wall 442:445 the plant cell wall 427:445 the plant cell wall 427:445 Ferulic acid dehydrodimers (DFA) and dehydrotrimers (TriFA) ester-linked to plant cell wall polymers may cross-link not only cell wall polysaccharides but also other cell wall components including proteins and lignin, thus enhancing the rigidity and potentially affecting the enzymatic degradation of the plant cell wall. 25660114 1 10 theme cell 251:254 arg1 lignin 336:341 lignin 336:341 lignin 336:341 Ferulic acid dehydrodimers (DFA) and dehydrotrimers (TriFA) ester-linked to plant cell wall polymers may cross-link not only cell wall polysaccharides but also other cell wall components including proteins and lignin, thus enhancing the rigidity and potentially affecting the enzymatic degradation of the plant cell wall. 25660114 1 10 theme cell 251:254 arg1 polysaccharides 261:275 cell wall polysaccharides 251:275 not only cell wall polysaccharides but also other cell wall components including proteins and lignin, thus enhancing the rigidity and potentially affecting the enzymatic degradation of the plant cell wall 242:445 Ferulic acid dehydrodimers (DFA) and dehydrotrimers (TriFA) ester-linked to plant cell wall polymers may cross-link not only cell wall polysaccharides but also other cell wall components including proteins and lignin, thus enhancing the rigidity and potentially affecting the enzymatic degradation of the plant cell wall. 25660114 1 10 theme cell 251:254 arg1 proteins 323:330 proteins 323:330 proteins 323:330 Ferulic acid dehydrodimers (DFA) and dehydrotrimers (TriFA) ester-linked to plant cell wall polymers may cross-link not only cell wall polysaccharides but also other cell wall components including proteins and lignin, thus enhancing the rigidity and potentially affecting the enzymatic degradation of the plant cell wall. 25660114 0 11 theme cereal 110:115 arg1 species 117:123 different cereal species 100:123 different cereal species 100:123 Ferulic acid dehydrodimer and dehydrotrimer profiles of distiller's dried grains with solubles from different cereal species. 25660114 2 12 theme high-performance 595:610 arg1 chromatography 619:632 reversed phase high-performance liquid chromatography 580:632 reversed phase high-performance liquid chromatography with ultraviolet detection 580:659 Corn, wheat, and mixed-cereal distiller's dried grains with solubles (DDGS) were investigated for composition of DFAs and TriFAs by reversed phase high-performance liquid chromatography with ultraviolet detection. 25660114 1 13 theme wall 442:445 arg1 degradation 412:422 the enzymatic degradation 398:422 the enzymatic degradation of the plant cell wall 398:445 Ferulic acid dehydrodimers (DFA) and dehydrotrimers (TriFA) ester-linked to plant cell wall polymers may cross-link not only cell wall polysaccharides but also other cell wall components including proteins and lignin, thus enhancing the rigidity and potentially affecting the enzymatic degradation of the plant cell wall. 25660114 0 14 theme different 100:108 arg1 species 117:123 different cereal species 100:123 different cereal species 100:123 Ferulic acid dehydrodimer and dehydrotrimer profiles of distiller's dried grains with solubles from different cereal species. 25660114 2 15 theme phase 589:593 arg1 chromatography 619:632 reversed phase high-performance liquid chromatography 580:632 reversed phase high-performance liquid chromatography with ultraviolet detection 580:659 Corn, wheat, and mixed-cereal distiller's dried grains with solubles (DDGS) were investigated for composition of DFAs and TriFAs by reversed phase high-performance liquid chromatography with ultraviolet detection. 25660114 5 16 theme corn 932:935 arg1 grains 937:942 corn grains 932:942 corn grains 932:942 In addition, both corn grains and corresponding DDGS had similar profiles of individual DFAs and TriFAs, indicating that ferulic acid cross-links in the corn cell wall are presumably not modified during fermentation and DDGS processing. 25660114 2 17 theme dried 490:494 arg1 grains 496:501 Corn, wheat, and mixed-cereal distiller's dried grains 448:501 Corn, wheat, and mixed-cereal distiller's dried grains with solubles (DDGS) 448:522 Corn, wheat, and mixed-cereal distiller's dried grains with solubles (DDGS) were investigated for composition of DFAs and TriFAs by reversed phase high-performance liquid chromatography with ultraviolet detection. 25660114 0 18 theme acid 8:11 arg1 dehydrodimer 13:24 Ferulic acid dehydrodimer 0:24 Ferulic acid dehydrodimer 0:24 Ferulic acid dehydrodimer and dehydrotrimer profiles of distiller's dried grains with solubles from different cereal species. 25660114 3 19 theme DFAs 725:728 arg1 contents 707:714 5.3 and 5.9 times higher contents 682:714 5.3 and 5.9 times higher contents of total DFAs 682:728 Corn DDGS contained 5.3 and 5.9 times higher contents of total DFAs than wheat and mixed-cereal DDGS, respectively. 25660114 2 20 theme reversed 580:587 arg1 chromatography 619:632 reversed phase high-performance liquid chromatography 580:632 reversed phase high-performance liquid chromatography with ultraviolet detection 580:659 Corn, wheat, and mixed-cereal distiller's dried grains with solubles (DDGS) were investigated for composition of DFAs and TriFAs by reversed phase high-performance liquid chromatography with ultraviolet detection. 25660114 2 21 with chromatography 619:632 arg1 detection 651:659 ultraviolet detection 639:659 ultraviolet detection 639:659 Corn, wheat, and mixed-cereal distiller's dried grains with solubles (DDGS) were investigated for composition of DFAs and TriFAs by reversed phase high-performance liquid chromatography with ultraviolet detection. 25660114 0 22 theme Ferulic 0:6 arg1 dehydrodimer 13:24 Ferulic acid dehydrodimer 0:24 Ferulic acid dehydrodimer 0:24 Ferulic acid dehydrodimer and dehydrotrimer profiles of distiller's dried grains with solubles from different cereal species. 25660114 1 23 theme wall 256:259 arg1 lignin 336:341 lignin 336:341 lignin 336:341 Ferulic acid dehydrodimers (DFA) and dehydrotrimers (TriFA) ester-linked to plant cell wall polymers may cross-link not only cell wall polysaccharides but also other cell wall components including proteins and lignin, thus enhancing the rigidity and potentially affecting the enzymatic degradation of the plant cell wall. 25660114 1 23 theme wall 256:259 arg1 polysaccharides 261:275 cell wall polysaccharides 251:275 not only cell wall polysaccharides but also other cell wall components including proteins and lignin, thus enhancing the rigidity and potentially affecting the enzymatic degradation of the plant cell wall 242:445 Ferulic acid dehydrodimers (DFA) and dehydrotrimers (TriFA) ester-linked to plant cell wall polymers may cross-link not only cell wall polysaccharides but also other cell wall components including proteins and lignin, thus enhancing the rigidity and potentially affecting the enzymatic degradation of the plant cell wall. 25660114 1 23 theme wall 256:259 arg1 proteins 323:330 proteins 323:330 proteins 323:330 Ferulic acid dehydrodimers (DFA) and dehydrotrimers (TriFA) ester-linked to plant cell wall polymers may cross-link not only cell wall polysaccharides but also other cell wall components including proteins and lignin, thus enhancing the rigidity and potentially affecting the enzymatic degradation of the plant cell wall. 25660114 3 24 dep contents 707:714 arg1 5.3 682:684 5.3 682:684 5.3 682:684 Corn DDGS contained 5.3 and 5.9 times higher contents of total DFAs than wheat and mixed-cereal DDGS, respectively. 25660114 3 24 dep contents 707:714 arg1 times 694:698 times 694:698 times 694:698 Corn DDGS contained 5.3 and 5.9 times higher contents of total DFAs than wheat and mixed-cereal DDGS, respectively. 25660114 5 25 theme individual 991:1000 arg1 DFAs 1002:1005 individual DFAs 991:1005 individual DFAs 991:1005 In addition, both corn grains and corresponding DDGS had similar profiles of individual DFAs and TriFAs, indicating that ferulic acid cross-links in the corn cell wall are presumably not modified during fermentation and DDGS processing. 25660114 3 26 dep 5.3 682:684 arg1 higher 700:705 higher 700:705 higher 700:705 Corn DDGS contained 5.3 and 5.9 times higher contents of total DFAs than wheat and mixed-cereal DDGS, respectively. 25660114 2 27 theme liquid 612:617 arg1 chromatography 619:632 reversed phase high-performance liquid chromatography 580:632 reversed phase high-performance liquid chromatography with ultraviolet detection 580:659 Corn, wheat, and mixed-cereal distiller's dried grains with solubles (DDGS) were investigated for composition of DFAs and TriFAs by reversed phase high-performance liquid chromatography with ultraviolet detection. 25660114 5 28 from cross-links 1048:1058 arg1 wall 1077:1080 the corn cell wall 1063:1080 the corn cell wall 1063:1080 In addition, both corn grains and corresponding DDGS had similar profiles of individual DFAs and TriFAs, indicating that ferulic acid cross-links in the corn cell wall are presumably not modified during fermentation and DDGS processing. 25660114 3 29 theme total 719:723 arg1 DFAs 725:728 total DFAs 719:728 total DFAs 719:728 Corn DDGS contained 5.3 and 5.9 times higher contents of total DFAs than wheat and mixed-cereal DDGS, respectively. 25660114 5 30 theme DDGS 1134:1137 arg1 processing 1139:1148 DDGS processing 1134:1148 DDGS processing 1134:1148 In addition, both corn grains and corresponding DDGS had similar profiles of individual DFAs and TriFAs, indicating that ferulic acid cross-links in the corn cell wall are presumably not modified during fermentation and DDGS processing. 25660114 1 31 theme ester-linked 186:197 arg1 DFA 154:156 DFA 154:156 DFA 154:156 Ferulic acid dehydrodimers (DFA) and dehydrotrimers (TriFA) ester-linked to plant cell wall polymers may cross-link not only cell wall polysaccharides but also other cell wall components including proteins and lignin, thus enhancing the rigidity and potentially affecting the enzymatic degradation of the plant cell wall. 25660114 1 31 theme ester-linked 186:197 arg1 dehydrodimers 139:151 Ferulic acid dehydrodimers 126:151 Ferulic acid dehydrodimers (DFA) 126:157 Ferulic acid dehydrodimers (DFA) and dehydrotrimers (TriFA) ester-linked to plant cell wall polymers may cross-link not only cell wall polysaccharides but also other cell wall components including proteins and lignin, thus enhancing the rigidity and potentially affecting the enzymatic degradation of the plant cell wall. 25660114 1 32 dep proteins 323:330 arg1 affecting 388:396 affecting 388:396 potentially affecting the enzymatic degradation of the plant cell wall 376:445 Ferulic acid dehydrodimers (DFA) and dehydrotrimers (TriFA) ester-linked to plant cell wall polymers may cross-link not only cell wall polysaccharides but also other cell wall components including proteins and lignin, thus enhancing the rigidity and potentially affecting the enzymatic degradation of the plant cell wall. 25660114 1 32 dep proteins 323:330 arg1 enhancing 349:357 enhancing 349:357 enhancing the rigidity 349:370 Ferulic acid dehydrodimers (DFA) and dehydrotrimers (TriFA) ester-linked to plant cell wall polymers may cross-link not only cell wall polysaccharides but also other cell wall components including proteins and lignin, thus enhancing the rigidity and potentially affecting the enzymatic degradation of the plant cell wall. 25660114 0 33 theme dehydrotrimer 30:42 arg1 profiles 44:51 dehydrotrimer profiles 30:51 dehydrotrimer profiles 30:51 Ferulic acid dehydrodimer and dehydrotrimer profiles of distiller's dried grains with solubles from different cereal species. 25660114 1 34 theme other 286:290 arg1 lignin 336:341 lignin 336:341 lignin 336:341 Ferulic acid dehydrodimers (DFA) and dehydrotrimers (TriFA) ester-linked to plant cell wall polymers may cross-link not only cell wall polysaccharides but also other cell wall components including proteins and lignin, thus enhancing the rigidity and potentially affecting the enzymatic degradation of the plant cell wall. 25660114 1 34 theme other 286:290 arg1 proteins 323:330 proteins 323:330 proteins 323:330 Ferulic acid dehydrodimers (DFA) and dehydrotrimers (TriFA) ester-linked to plant cell wall polymers may cross-link not only cell wall polysaccharides but also other cell wall components including proteins and lignin, thus enhancing the rigidity and potentially affecting the enzymatic degradation of the plant cell wall. 25660114 1 34 theme other 286:290 arg1 components 302:311 other cell wall components 286:311 not only cell wall polysaccharides but also other cell wall components including proteins and lignin, thus enhancing the rigidity and potentially affecting the enzymatic degradation of the plant cell wall 242:445 Ferulic acid dehydrodimers (DFA) and dehydrotrimers (TriFA) ester-linked to plant cell wall polymers may cross-link not only cell wall polysaccharides but also other cell wall components including proteins and lignin, thus enhancing the rigidity and potentially affecting the enzymatic degradation of the plant cell wall. 25660114 4 35 theme mixed-cereal 881:892 arg1 DDGS 894:897 mixed-cereal DDGS 881:897 mixed-cereal DDGS 881:897 Furthermore, the contents of total TriFAs were 5.7 and 6.3 times higher in corn DDGS than in wheat and mixed-cereal DDGS, respectively. 25660114 5 36 theme similar 971:977 arg1 profiles 979:986 similar profiles 971:986 similar profiles of individual DFAs and TriFAs 971:1016 In addition, both corn grains and corresponding DDGS had similar profiles of individual DFAs and TriFAs, indicating that ferulic acid cross-links in the corn cell wall are presumably not modified during fermentation and DDGS processing. 25660114 1 37 theme plant 202:206 arg1 polymers 218:225 plant cell wall polymers 202:225 plant cell wall polymers 202:225 Ferulic acid dehydrodimers (DFA) and dehydrotrimers (TriFA) ester-linked to plant cell wall polymers may cross-link not only cell wall polysaccharides but also other cell wall components including proteins and lignin, thus enhancing the rigidity and potentially affecting the enzymatic degradation of the plant cell wall. 25660114 1 38 theme cell 292:295 arg1 lignin 336:341 lignin 336:341 lignin 336:341 Ferulic acid dehydrodimers (DFA) and dehydrotrimers (TriFA) ester-linked to plant cell wall polymers may cross-link not only cell wall polysaccharides but also other cell wall components including proteins and lignin, thus enhancing the rigidity and potentially affecting the enzymatic degradation of the plant cell wall. 25660114 1 38 theme cell 292:295 arg1 proteins 323:330 proteins 323:330 proteins 323:330 Ferulic acid dehydrodimers (DFA) and dehydrotrimers (TriFA) ester-linked to plant cell wall polymers may cross-link not only cell wall polysaccharides but also other cell wall components including proteins and lignin, thus enhancing the rigidity and potentially affecting the enzymatic degradation of the plant cell wall. 25660114 1 38 theme cell 292:295 arg1 components 302:311 other cell wall components 286:311 not only cell wall polysaccharides but also other cell wall components including proteins and lignin, thus enhancing the rigidity and potentially affecting the enzymatic degradation of the plant cell wall 242:445 Ferulic acid dehydrodimers (DFA) and dehydrotrimers (TriFA) ester-linked to plant cell wall polymers may cross-link not only cell wall polysaccharides but also other cell wall components including proteins and lignin, thus enhancing the rigidity and potentially affecting the enzymatic degradation of the plant cell wall. 25660114 5 39 theme DFAs 1002:1005 arg1 profiles 979:986 similar profiles 971:986 similar profiles of individual DFAs and TriFAs 971:1016 In addition, both corn grains and corresponding DDGS had similar profiles of individual DFAs and TriFAs, indicating that ferulic acid cross-links in the corn cell wall are presumably not modified during fermentation and DDGS processing. 25660114 4 40 theme total 807:811 arg1 TriFAs 813:818 total TriFAs 807:818 total TriFAs 807:818 Furthermore, the contents of total TriFAs were 5.7 and 6.3 times higher in corn DDGS than in wheat and mixed-cereal DDGS, respectively. 25660114 0 41 with dehydrodimer 13:24 arg1 solubles 86:93 solubles 86:93 solubles from different cereal species 86:123 Ferulic acid dehydrodimer and dehydrotrimer profiles of distiller's dried grains with solubles from different cereal species. 25660114 1 42 theme wall 297:300 arg1 lignin 336:341 lignin 336:341 lignin 336:341 Ferulic acid dehydrodimers (DFA) and dehydrotrimers (TriFA) ester-linked to plant cell wall polymers may cross-link not only cell wall polysaccharides but also other cell wall components including proteins and lignin, thus enhancing the rigidity and potentially affecting the enzymatic degradation of the plant cell wall. 25660114 1 42 theme wall 297:300 arg1 proteins 323:330 proteins 323:330 proteins 323:330 Ferulic acid dehydrodimers (DFA) and dehydrotrimers (TriFA) ester-linked to plant cell wall polymers may cross-link not only cell wall polysaccharides but also other cell wall components including proteins and lignin, thus enhancing the rigidity and potentially affecting the enzymatic degradation of the plant cell wall. 25660114 1 42 theme wall 297:300 arg1 components 302:311 other cell wall components 286:311 not only cell wall polysaccharides but also other cell wall components including proteins and lignin, thus enhancing the rigidity and potentially affecting the enzymatic degradation of the plant cell wall 242:445 Ferulic acid dehydrodimers (DFA) and dehydrotrimers (TriFA) ester-linked to plant cell wall polymers may cross-link not only cell wall polysaccharides but also other cell wall components including proteins and lignin, thus enhancing the rigidity and potentially affecting the enzymatic degradation of the plant cell wall. 25660114 4 43 theme corn 853:856 arg1 DDGS 858:861 corn DDGS 853:861 corn DDGS 853:861 Furthermore, the contents of total TriFAs were 5.7 and 6.3 times higher in corn DDGS than in wheat and mixed-cereal DDGS, respectively. 25660114 3 44 theme Corn 662:665 arg1 DDGS 667:670 Corn DDGS 662:670 Corn DDGS 662:670 Corn DDGS contained 5.3 and 5.9 times higher contents of total DFAs than wheat and mixed-cereal DDGS, respectively. 25660114 4 45 theme TriFAs 813:818 arg1 contents 795:802 the contents 791:802 the contents of total TriFAs 791:818 Furthermore, the contents of total TriFAs were 5.7 and 6.3 times higher in corn DDGS than in wheat and mixed-cereal DDGS, respectively. 25660114 4 45 theme TriFAs 813:818 arg1 higher 843:848 higher 843:848 higher 843:848 Furthermore, the contents of total TriFAs were 5.7 and 6.3 times higher in corn DDGS than in wheat and mixed-cereal DDGS, respectively. 25660114 2 46 with grains 496:501 arg1 DDGS 518:521 DDGS 518:521 DDGS 518:521 Corn, wheat, and mixed-cereal distiller's dried grains with solubles (DDGS) were investigated for composition of DFAs and TriFAs by reversed phase high-performance liquid chromatography with ultraviolet detection. 25660114 2 46 with grains 496:501 arg1 solubles 508:515 solubles 508:515 solubles (DDGS) 508:522 Corn, wheat, and mixed-cereal distiller's dried grains with solubles (DDGS) were investigated for composition of DFAs and TriFAs by reversed phase high-performance liquid chromatography with ultraviolet detection. 25660114 1 47 theme enzymatic 402:410 arg1 degradation 412:422 the enzymatic degradation 398:422 the enzymatic degradation of the plant cell wall 398:445 Ferulic acid dehydrodimers (DFA) and dehydrotrimers (TriFA) ester-linked to plant cell wall polymers may cross-link not only cell wall polysaccharides but also other cell wall components including proteins and lignin, thus enhancing the rigidity and potentially affecting the enzymatic degradation of the plant cell wall. 25660114 1 48 theme Ferulic 126:132 arg1 DFA 154:156 DFA 154:156 DFA 154:156 Ferulic acid dehydrodimers (DFA) and dehydrotrimers (TriFA) ester-linked to plant cell wall polymers may cross-link not only cell wall polysaccharides but also other cell wall components including proteins and lignin, thus enhancing the rigidity and potentially affecting the enzymatic degradation of the plant cell wall. 25660114 1 48 theme Ferulic 126:132 arg1 dehydrodimers 139:151 Ferulic acid dehydrodimers 126:151 Ferulic acid dehydrodimers (DFA) 126:157 Ferulic acid dehydrodimers (DFA) and dehydrotrimers (TriFA) ester-linked to plant cell wall polymers may cross-link not only cell wall polysaccharides but also other cell wall components including proteins and lignin, thus enhancing the rigidity and potentially affecting the enzymatic degradation of the plant cell wall. 25660114 1 49 theme cell 208:211 arg1 polymers 218:225 plant cell wall polymers 202:225 plant cell wall polymers 202:225 Ferulic acid dehydrodimers (DFA) and dehydrotrimers (TriFA) ester-linked to plant cell wall polymers may cross-link not only cell wall polysaccharides but also other cell wall components including proteins and lignin, thus enhancing the rigidity and potentially affecting the enzymatic degradation of the plant cell wall. 25660114 3 50 theme mixed-cereal 745:756 arg1 DDGS 758:761 mixed-cereal DDGS 745:761 mixed-cereal DDGS 745:761 Corn DDGS contained 5.3 and 5.9 times higher contents of total DFAs than wheat and mixed-cereal DDGS, respectively. 25660114 1 51 theme acid 134:137 arg1 DFA 154:156 DFA 154:156 DFA 154:156 Ferulic acid dehydrodimers (DFA) and dehydrotrimers (TriFA) ester-linked to plant cell wall polymers may cross-link not only cell wall polysaccharides but also other cell wall components including proteins and lignin, thus enhancing the rigidity and potentially affecting the enzymatic degradation of the plant cell wall. 25660114 1 51 theme acid 134:137 arg1 dehydrodimers 139:151 Ferulic acid dehydrodimers 126:151 Ferulic acid dehydrodimers (DFA) 126:157 Ferulic acid dehydrodimers (DFA) and dehydrotrimers (TriFA) ester-linked to plant cell wall polymers may cross-link not only cell wall polysaccharides but also other cell wall components including proteins and lignin, thus enhancing the rigidity and potentially affecting the enzymatic degradation of the plant cell wall. 25660114 1 52 theme wall 213:216 arg1 polymers 218:225 plant cell wall polymers 202:225 plant cell wall polymers 202:225 Ferulic acid dehydrodimers (DFA) and dehydrotrimers (TriFA) ester-linked to plant cell wall polymers may cross-link not only cell wall polysaccharides but also other cell wall components including proteins and lignin, thus enhancing the rigidity and potentially affecting the enzymatic degradation of the plant cell wall. 25660114 0 53 theme dried 68:72 arg1 grains 74:79 distiller's dried grains 56:79 distiller's dried grains 56:79 Ferulic acid dehydrodimer and dehydrotrimer profiles of distiller's dried grains with solubles from different cereal species. 25660114 5 54 theme TriFAs 1011:1016 arg1 profiles 979:986 similar profiles 971:986 similar profiles of individual DFAs and TriFAs 971:1016 In addition, both corn grains and corresponding DDGS had similar profiles of individual DFAs and TriFAs, indicating that ferulic acid cross-links in the corn cell wall are presumably not modified during fermentation and DDGS processing. 25660114 5 55 theme corresponding 948:960 arg1 DDGS 962:965 corresponding DDGS 948:965 corresponding DDGS 948:965 In addition, both corn grains and corresponding DDGS had similar profiles of individual DFAs and TriFAs, indicating that ferulic acid cross-links in the corn cell wall are presumably not modified during fermentation and DDGS processing. 25660114 5 56 contain had 967:969 arg1 grains 937:942 corn grains 932:942 corn grains 932:942 In addition, both corn grains and corresponding DDGS had similar profiles of individual DFAs and TriFAs, indicating that ferulic acid cross-links in the corn cell wall are presumably not modified during fermentation and DDGS processing. 25660114 5 56 contain had 967:969 arg2 profiles 979:986 similar profiles 971:986 similar profiles of individual DFAs and TriFAs 971:1016 In addition, both corn grains and corresponding DDGS had similar profiles of individual DFAs and TriFAs, indicating that ferulic acid cross-links in the corn cell wall are presumably not modified during fermentation and DDGS processing. 25660114 5 56 contain had 967:969 arg1 DDGS 962:965 corresponding DDGS 948:965 corresponding DDGS 948:965 In addition, both corn grains and corresponding DDGS had similar profiles of individual DFAs and TriFAs, indicating that ferulic acid cross-links in the corn cell wall are presumably not modified during fermentation and DDGS processing. 25660114 2 57 theme mixed-cereal 465:476 arg1 distiller 478:486 mixed-cereal distiller 465:486 mixed-cereal distiller 465:486 Corn, wheat, and mixed-cereal distiller's dried grains with solubles (DDGS) were investigated for composition of DFAs and TriFAs by reversed phase high-performance liquid chromatography with ultraviolet detection. 25660114 5 58 theme corn 1067:1070 arg1 wall 1077:1080 the corn cell wall 1063:1080 the corn cell wall 1063:1080 In addition, both corn grains and corresponding DDGS had similar profiles of individual DFAs and TriFAs, indicating that ferulic acid cross-links in the corn cell wall are presumably not modified during fermentation and DDGS processing. 25660114 0 59 with profiles 44:51 arg1 solubles 86:93 solubles 86:93 solubles from different cereal species 86:123 Ferulic acid dehydrodimer and dehydrotrimer profiles of distiller's dried grains with solubles from different cereal species. 25660114 3 60 contain contained 672:680 arg2 contents 707:714 5.3 and 5.9 times higher contents 682:714 5.3 and 5.9 times higher contents of total DFAs 682:728 Corn DDGS contained 5.3 and 5.9 times higher contents of total DFAs than wheat and mixed-cereal DDGS, respectively. 25660114 3 60 contain contained 672:680 arg1 DDGS 667:670 Corn DDGS 662:670 Corn DDGS 662:670 Corn DDGS contained 5.3 and 5.9 times higher contents of total DFAs than wheat and mixed-cereal DDGS, respectively. 25660114 0 61 from species 117:123 arg1 solubles 86:93 solubles 86:93 solubles from different cereal species 86:123 Ferulic acid dehydrodimer and dehydrotrimer profiles of distiller's dried grains with solubles from different cereal species. 27775058 3 0 dep proteome 355:362 arg1 The 351:353 The 351:353 The 351:353 The proteome, lipidome, RNA content, and carbohydrate composition of EVs from Paracoccidioides brasiliensis and Paracoccidioides lutzii were characterized. 27775058 7 1 theme markers 976:982 arg1 expression 946:955 the augmented expression 932:955 the augmented expression of M2-polarization markers, stimulated by IL-4 plus IL-10, 932:1014 Furthermore, the augmented expression of M2-polarization markers, stimulated by IL-4 plus IL-10, was reverted toward an M1 phenotype in response to secondary stimulation with EVs from P. brasiliensis. 27775058 2 2 theme infection 340:348 arg1 pathogenesis 324:335 the pathogenesis 320:335 the pathogenesis of infection 320:348 The cargo analysis of EVs shows that they contain virulence factors suggesting a role in the pathogenesis of infection. 27775058 4 3 theme immune 563:568 arg1 system 570:575 the host immune system 554:575 the host immune system 554:575 However, the effects of P. brasiliensis EVs on the host immune system have not yet been investigated. 27775058 5 4 theme murine 713:718 arg1 macrophages 720:730 murine macrophages 713:730 murine macrophages 713:730 Herein, we verified that EVs from P. brasiliensis induce the production of proinflammatory mediators by murine macrophages in a dose-dependent manner. 27775058 8 5 from brasiliensis 1147:1158 arg1 EVs 1135:1137 EVs 1135:1137 EVs from P. brasiliensis 1135:1158 The ability of EVs from P. brasiliensis to promote M1 polarization macrophages favoring an enhanced fungicidal activity, demonstrated by the decreased CFU recovery of internalized yeasts, with comparable phagocytic efficacy. 27775058 8 5 from brasiliensis 1147:1158 arg1 ability 1124:1130 The ability 1120:1130 The ability 1120:1130 The ability of EVs from P. brasiliensis to promote M1 polarization macrophages favoring an enhanced fungicidal activity, demonstrated by the decreased CFU recovery of internalized yeasts, with comparable phagocytic efficacy. 27775058 7 6 from phenotype 1042:1050 arg1 response 1055:1062 response 1055:1062 response to secondary stimulation with EVs from P. brasiliensis 1055:1117 Furthermore, the augmented expression of M2-polarization markers, stimulated by IL-4 plus IL-10, was reverted toward an M1 phenotype in response to secondary stimulation with EVs from P. brasiliensis. 27775058 8 7 theme phagocytic 1324:1333 arg1 efficacy 1335:1342 comparable phagocytic efficacy 1313:1342 comparable phagocytic efficacy 1313:1342 The ability of EVs from P. brasiliensis to promote M1 polarization macrophages favoring an enhanced fungicidal activity, demonstrated by the decreased CFU recovery of internalized yeasts, with comparable phagocytic efficacy. 27775058 8 8 theme comparable 1313:1322 arg1 efficacy 1335:1342 comparable phagocytic efficacy 1313:1342 comparable phagocytic efficacy 1313:1342 The ability of EVs from P. brasiliensis to promote M1 polarization macrophages favoring an enhanced fungicidal activity, demonstrated by the decreased CFU recovery of internalized yeasts, with comparable phagocytic efficacy. 27775058 9 9 theme immune 1419:1424 arg1 response 1426:1433 the innate immune response 1408:1433 the innate immune response 1408:1433 Our results suggest that EVs from P. brasiliensis can modulate the innate immune response and affect the relationship between P. brasiliensis and host immune cells. 27775058 7 10 theme secondary 1067:1075 arg1 stimulation 1077:1087 secondary stimulation 1067:1087 secondary stimulation with EVs from P. brasiliensis 1067:1117 Furthermore, the augmented expression of M2-polarization markers, stimulated by IL-4 plus IL-10, was reverted toward an M1 phenotype in response to secondary stimulation with EVs from P. brasiliensis. 27775058 7 11 theme augmented 936:944 arg1 expression 946:955 the augmented expression 932:955 the augmented expression of M2-polarization markers, stimulated by IL-4 plus IL-10, 932:1014 Furthermore, the augmented expression of M2-polarization markers, stimulated by IL-4 plus IL-10, was reverted toward an M1 phenotype in response to secondary stimulation with EVs from P. brasiliensis. 27775058 8 12 theme fungicidal 1220:1229 arg1 activity 1231:1238 an enhanced fungicidal activity 1208:1238 an enhanced fungicidal activity 1208:1238 The ability of EVs from P. brasiliensis to promote M1 polarization macrophages favoring an enhanced fungicidal activity, demonstrated by the decreased CFU recovery of internalized yeasts, with comparable phagocytic efficacy. 27775058 4 13 from effects 520:526 arg1 system 570:575 the host immune system 554:575 the host immune system 554:575 However, the effects of P. brasiliensis EVs on the host immune system have not yet been investigated. 27775058 6 14 theme M2 878:879 arg1 markers 881:887 the M2 markers Arginase-1, Ym-1, and FIZZ-1 874:916 the M2 markers Arginase-1, Ym-1, and FIZZ-1 874:916 Addition of EV to macrophages also promoted transcription of the M1-polarization marker iNOs and diminish that of the M2 markers Arginase-1, Ym-1, and FIZZ-1. 27775058 6 14 theme M2 878:879 arg1 Ym-1 901:904 Ym-1 901:904 Ym-1 901:904 Addition of EV to macrophages also promoted transcription of the M1-polarization marker iNOs and diminish that of the M2 markers Arginase-1, Ym-1, and FIZZ-1. 27775058 6 14 theme M2 878:879 arg1 FIZZ-1 911:916 FIZZ-1 911:916 FIZZ-1 911:916 Addition of EV to macrophages also promoted transcription of the M1-polarization marker iNOs and diminish that of the M2 markers Arginase-1, Ym-1, and FIZZ-1. 27775058 6 14 theme M2 878:879 arg1 Arginase-1 889:898 Arginase-1 889:898 Arginase-1 889:898 Addition of EV to macrophages also promoted transcription of the M1-polarization marker iNOs and diminish that of the M2 markers Arginase-1, Ym-1, and FIZZ-1. 27775058 1 15 theme Extracellular 92:104 arg1 EVs 116:118 EVs 116:118 EVs 116:118 Extracellular vesicles (EVs) released by eukaryotes, archaea, and bacteria contain proteins, lipids, polysaccharides, and other molecules. 27775058 1 15 theme Extracellular 92:104 arg1 vesicles 106:113 Extracellular vesicles 92:113 Extracellular vesicles (EVs) released by eukaryotes, archaea, and bacteria 92:165 Extracellular vesicles (EVs) released by eukaryotes, archaea, and bacteria contain proteins, lipids, polysaccharides, and other molecules. 27775058 3 16 theme EVs 420:422 arg1 lipidome 365:372 lipidome 365:372 lipidome 365:372 The proteome, lipidome, RNA content, and carbohydrate composition of EVs from Paracoccidioides brasiliensis and Paracoccidioides lutzii were characterized. 27775058 3 16 theme EVs 420:422 arg1 content 379:385 RNA content 375:385 RNA content 375:385 The proteome, lipidome, RNA content, and carbohydrate composition of EVs from Paracoccidioides brasiliensis and Paracoccidioides lutzii were characterized. 27775058 3 16 theme EVs 420:422 arg1 proteome 355:362 proteome 355:362 proteome 355:362 The proteome, lipidome, RNA content, and carbohydrate composition of EVs from Paracoccidioides brasiliensis and Paracoccidioides lutzii were characterized. 27775058 3 16 theme EVs 420:422 arg1 composition 405:415 carbohydrate composition 392:415 carbohydrate composition 392:415 The proteome, lipidome, RNA content, and carbohydrate composition of EVs from Paracoccidioides brasiliensis and Paracoccidioides lutzii were characterized. 27775058 0 17 from brasiliensis 45:56 arg1 vesicles 14:21 Extracellular vesicles 0:21 Extracellular vesicles from Paracoccidioides brasiliensis 0:56 Extracellular vesicles from Paracoccidioides brasiliensis induced M1 polarization in vitro. 27775058 3 18 from lutzii 480:485 arg1 lipidome 365:372 lipidome 365:372 lipidome 365:372 The proteome, lipidome, RNA content, and carbohydrate composition of EVs from Paracoccidioides brasiliensis and Paracoccidioides lutzii were characterized. 27775058 3 18 from lutzii 480:485 arg1 content 379:385 RNA content 375:385 RNA content 375:385 The proteome, lipidome, RNA content, and carbohydrate composition of EVs from Paracoccidioides brasiliensis and Paracoccidioides lutzii were characterized. 27775058 3 18 from lutzii 480:485 arg1 proteome 355:362 proteome 355:362 proteome 355:362 The proteome, lipidome, RNA content, and carbohydrate composition of EVs from Paracoccidioides brasiliensis and Paracoccidioides lutzii were characterized. 27775058 3 18 from lutzii 480:485 arg1 composition 405:415 carbohydrate composition 392:415 carbohydrate composition 392:415 The proteome, lipidome, RNA content, and carbohydrate composition of EVs from Paracoccidioides brasiliensis and Paracoccidioides lutzii were characterized. 27775058 3 19 theme carbohydrate 392:403 arg1 composition 405:415 carbohydrate composition 392:415 carbohydrate composition 392:415 The proteome, lipidome, RNA content, and carbohydrate composition of EVs from Paracoccidioides brasiliensis and Paracoccidioides lutzii were characterized. 27775058 0 20 theme Extracellular 0:12 arg1 vesicles 14:21 Extracellular vesicles 0:21 Extracellular vesicles from Paracoccidioides brasiliensis 0:56 Extracellular vesicles from Paracoccidioides brasiliensis induced M1 polarization in vitro. 27775058 6 21 theme EV 772:773 arg1 Addition 760:767 Addition 760:767 Addition of EV to macrophages 760:788 Addition of EV to macrophages also promoted transcription of the M1-polarization marker iNOs and diminish that of the M2 markers Arginase-1, Ym-1, and FIZZ-1. 27775058 8 22 dep ability 1124:1130 arg1 promote 1163:1169 promote 1163:1169 to promote M1 polarization macrophages favoring an enhanced fungicidal activity 1160:1238 The ability of EVs from P. brasiliensis to promote M1 polarization macrophages favoring an enhanced fungicidal activity, demonstrated by the decreased CFU recovery of internalized yeasts, with comparable phagocytic efficacy. 27775058 0 23 theme Paracoccidioides 28:43 arg1 brasiliensis 45:56 Paracoccidioides brasiliensis 28:56 Paracoccidioides brasiliensis 28:56 Extracellular vesicles from Paracoccidioides brasiliensis induced M1 polarization in vitro. 27775058 4 24 theme EVs 547:549 arg1 effects 520:526 the effects 516:526 the effects of P. brasiliensis EVs on the host immune system 516:575 However, the effects of P. brasiliensis EVs on the host immune system have not yet been investigated. 27775058 4 25 theme host 558:561 arg1 system 570:575 the host immune system 554:575 the host immune system 554:575 However, the effects of P. brasiliensis EVs on the host immune system have not yet been investigated. 27775058 5 26 theme proinflammatory 684:698 arg1 mediators 700:708 proinflammatory mediators 684:708 proinflammatory mediators 684:708 Herein, we verified that EVs from P. brasiliensis induce the production of proinflammatory mediators by murine macrophages in a dose-dependent manner. 27775058 8 27 from ability 1124:1130 arg1 brasiliensis 1147:1158 P. brasiliensis 1144:1158 P. brasiliensis 1144:1158 The ability of EVs from P. brasiliensis to promote M1 polarization macrophages favoring an enhanced fungicidal activity, demonstrated by the decreased CFU recovery of internalized yeasts, with comparable phagocytic efficacy. 27775058 2 28 theme virulence 281:289 arg1 factors 291:297 virulence factors 281:297 virulence factors suggesting a role in the pathogenesis of infection 281:348 The cargo analysis of EVs shows that they contain virulence factors suggesting a role in the pathogenesis of infection. 27775058 2 29 contain contain 273:279 arg1 they 268:271 they 268:271 they 268:271 The cargo analysis of EVs shows that they contain virulence factors suggesting a role in the pathogenesis of infection. 27775058 2 29 contain contain 273:279 arg2 factors 291:297 virulence factors 281:297 virulence factors suggesting a role in the pathogenesis of infection 281:348 The cargo analysis of EVs shows that they contain virulence factors suggesting a role in the pathogenesis of infection. 27775058 5 30 theme mediators 700:708 arg1 production 670:679 the production 666:679 the production of proinflammatory mediators by murine macrophages 666:730 Herein, we verified that EVs from P. brasiliensis induce the production of proinflammatory mediators by murine macrophages in a dose-dependent manner. 27775058 8 31 theme decreased 1261:1269 arg1 recovery 1275:1282 the decreased CFU recovery 1257:1282 the decreased CFU recovery of internalized yeasts 1257:1305 The ability of EVs from P. brasiliensis to promote M1 polarization macrophages favoring an enhanced fungicidal activity, demonstrated by the decreased CFU recovery of internalized yeasts, with comparable phagocytic efficacy. 27775058 8 32 theme polarization 1174:1185 arg1 macrophages 1187:1197 M1 polarization macrophages 1171:1197 M1 polarization macrophages favoring an enhanced fungicidal activity 1171:1238 The ability of EVs from P. brasiliensis to promote M1 polarization macrophages favoring an enhanced fungicidal activity, demonstrated by the decreased CFU recovery of internalized yeasts, with comparable phagocytic efficacy. 27775058 7 33 theme M1 1039:1040 arg1 phenotype 1042:1050 an M1 phenotype 1036:1050 an M1 phenotype in response to secondary stimulation with EVs from P. brasiliensis 1036:1117 Furthermore, the augmented expression of M2-polarization markers, stimulated by IL-4 plus IL-10, was reverted toward an M1 phenotype in response to secondary stimulation with EVs from P. brasiliensis. 27775058 8 34 theme M1 1171:1172 arg1 macrophages 1187:1197 M1 polarization macrophages 1171:1197 M1 polarization macrophages favoring an enhanced fungicidal activity 1171:1238 The ability of EVs from P. brasiliensis to promote M1 polarization macrophages favoring an enhanced fungicidal activity, demonstrated by the decreased CFU recovery of internalized yeasts, with comparable phagocytic efficacy. 27775058 3 35 theme RNA 375:377 arg1 content 379:385 RNA content 375:385 RNA content 375:385 The proteome, lipidome, RNA content, and carbohydrate composition of EVs from Paracoccidioides brasiliensis and Paracoccidioides lutzii were characterized. 27775058 8 36 theme EVs 1135:1137 arg1 ability 1124:1130 The ability 1120:1130 The ability 1120:1130 The ability of EVs from P. brasiliensis to promote M1 polarization macrophages favoring an enhanced fungicidal activity, demonstrated by the decreased CFU recovery of internalized yeasts, with comparable phagocytic efficacy. 27775058 9 37 from brasiliensis 1382:1393 arg1 EVs 1370:1372 EVs 1370:1372 EVs from P. brasiliensis 1370:1393 Our results suggest that EVs from P. brasiliensis can modulate the innate immune response and affect the relationship between P. brasiliensis and host immune cells. 27775058 1 38 contain contain 167:173 arg1 EVs 116:118 EVs 116:118 EVs 116:118 Extracellular vesicles (EVs) released by eukaryotes, archaea, and bacteria contain proteins, lipids, polysaccharides, and other molecules. 27775058 1 38 contain contain 167:173 arg2 proteins 175:182 proteins 175:182 proteins 175:182 Extracellular vesicles (EVs) released by eukaryotes, archaea, and bacteria contain proteins, lipids, polysaccharides, and other molecules. 27775058 1 38 contain contain 167:173 arg2 lipids 185:190 lipids 185:190 lipids 185:190 Extracellular vesicles (EVs) released by eukaryotes, archaea, and bacteria contain proteins, lipids, polysaccharides, and other molecules. 27775058 1 38 contain contain 167:173 arg2 molecules 220:228 other molecules 214:228 other molecules 214:228 Extracellular vesicles (EVs) released by eukaryotes, archaea, and bacteria contain proteins, lipids, polysaccharides, and other molecules. 27775058 1 38 contain contain 167:173 arg2 polysaccharides 193:207 polysaccharides 193:207 polysaccharides 193:207 Extracellular vesicles (EVs) released by eukaryotes, archaea, and bacteria contain proteins, lipids, polysaccharides, and other molecules. 27775058 1 38 contain contain 167:173 arg1 vesicles 106:113 Extracellular vesicles 92:113 Extracellular vesicles (EVs) released by eukaryotes, archaea, and bacteria 92:165 Extracellular vesicles (EVs) released by eukaryotes, archaea, and bacteria contain proteins, lipids, polysaccharides, and other molecules. 27775058 0 39 theme M1 66:67 arg1 polarization 69:80 M1 polarization 66:80 M1 polarization 66:80 Extracellular vesicles from Paracoccidioides brasiliensis induced M1 polarization in vitro. 27775058 4 40 theme brasiliensis 534:545 arg1 EVs 547:549 P. brasiliensis EVs 531:549 P. brasiliensis EVs 531:549 However, the effects of P. brasiliensis EVs on the host immune system have not yet been investigated. 27775058 6 41 theme iNOs 848:851 arg1 transcription 804:816 transcription 804:816 transcription of the M1-polarization marker iNOs 804:851 Addition of EV to macrophages also promoted transcription of the M1-polarization marker iNOs and diminish that of the M2 markers Arginase-1, Ym-1, and FIZZ-1. 27775058 3 42 from brasiliensis 446:457 arg1 lipidome 365:372 lipidome 365:372 lipidome 365:372 The proteome, lipidome, RNA content, and carbohydrate composition of EVs from Paracoccidioides brasiliensis and Paracoccidioides lutzii were characterized. 27775058 3 42 from brasiliensis 446:457 arg1 content 379:385 RNA content 375:385 RNA content 375:385 The proteome, lipidome, RNA content, and carbohydrate composition of EVs from Paracoccidioides brasiliensis and Paracoccidioides lutzii were characterized. 27775058 3 42 from brasiliensis 446:457 arg1 proteome 355:362 proteome 355:362 proteome 355:362 The proteome, lipidome, RNA content, and carbohydrate composition of EVs from Paracoccidioides brasiliensis and Paracoccidioides lutzii were characterized. 27775058 3 42 from brasiliensis 446:457 arg1 composition 405:415 carbohydrate composition 392:415 carbohydrate composition 392:415 The proteome, lipidome, RNA content, and carbohydrate composition of EVs from Paracoccidioides brasiliensis and Paracoccidioides lutzii were characterized. 27775058 8 43 theme CFU 1271:1273 arg1 recovery 1275:1282 the decreased CFU recovery 1257:1282 the decreased CFU recovery of internalized yeasts 1257:1305 The ability of EVs from P. brasiliensis to promote M1 polarization macrophages favoring an enhanced fungicidal activity, demonstrated by the decreased CFU recovery of internalized yeasts, with comparable phagocytic efficacy. 27775058 4 44 theme P. 531:532 arg1 EVs 547:549 P. brasiliensis EVs 531:549 P. brasiliensis EVs 531:549 However, the effects of P. brasiliensis EVs on the host immune system have not yet been investigated. 27775058 6 45 theme marker 841:846 arg1 iNOs 848:851 the M1-polarization marker iNOs 821:851 the M1-polarization marker iNOs 821:851 Addition of EV to macrophages also promoted transcription of the M1-polarization marker iNOs and diminish that of the M2 markers Arginase-1, Ym-1, and FIZZ-1. 27775058 2 46 theme EVs 253:255 arg1 analysis 241:248 The cargo analysis 231:248 The cargo analysis of EVs 231:255 The cargo analysis of EVs shows that they contain virulence factors suggesting a role in the pathogenesis of infection. 27775058 8 47 theme internalized 1287:1298 arg1 yeasts 1300:1305 internalized yeasts 1287:1305 internalized yeasts 1287:1305 The ability of EVs from P. brasiliensis to promote M1 polarization macrophages favoring an enhanced fungicidal activity, demonstrated by the decreased CFU recovery of internalized yeasts, with comparable phagocytic efficacy. 27775058 1 48 theme other 214:218 arg1 molecules 220:228 other molecules 214:228 other molecules 214:228 Extracellular vesicles (EVs) released by eukaryotes, archaea, and bacteria contain proteins, lipids, polysaccharides, and other molecules. 27775058 6 49 theme M1-polarization 825:839 arg1 iNOs 848:851 the M1-polarization marker iNOs 821:851 the M1-polarization marker iNOs 821:851 Addition of EV to macrophages also promoted transcription of the M1-polarization marker iNOs and diminish that of the M2 markers Arginase-1, Ym-1, and FIZZ-1. 27775058 7 50 with stimulation 1077:1087 arg1 EVs 1094:1096 EVs 1094:1096 EVs from P. brasiliensis 1094:1117 Furthermore, the augmented expression of M2-polarization markers, stimulated by IL-4 plus IL-10, was reverted toward an M1 phenotype in response to secondary stimulation with EVs from P. brasiliensis. 27775058 9 51 theme immune 1496:1501 arg1 cells 1503:1507 host immune cells 1491:1507 host immune cells 1491:1507 Our results suggest that EVs from P. brasiliensis can modulate the innate immune response and affect the relationship between P. brasiliensis and host immune cells. 27775058 5 52 theme dose-dependent 737:750 arg1 manner 752:757 a dose-dependent manner 735:757 a dose-dependent manner 735:757 Herein, we verified that EVs from P. brasiliensis induce the production of proinflammatory mediators by murine macrophages in a dose-dependent manner. 27775058 9 53 theme host 1491:1494 arg1 cells 1503:1507 host immune cells 1491:1507 host immune cells 1491:1507 Our results suggest that EVs from P. brasiliensis can modulate the innate immune response and affect the relationship between P. brasiliensis and host immune cells. 27775058 8 54 theme enhanced 1211:1218 arg1 activity 1231:1238 an enhanced fungicidal activity 1208:1238 an enhanced fungicidal activity 1208:1238 The ability of EVs from P. brasiliensis to promote M1 polarization macrophages favoring an enhanced fungicidal activity, demonstrated by the decreased CFU recovery of internalized yeasts, with comparable phagocytic efficacy. 27775058 5 55 from brasiliensis 646:657 arg1 EVs 634:636 EVs 634:636 EVs from P. brasiliensis 634:657 Herein, we verified that EVs from P. brasiliensis induce the production of proinflammatory mediators by murine macrophages in a dose-dependent manner. 27775058 9 56 theme innate 1412:1417 arg1 response 1426:1433 the innate immune response 1408:1433 the innate immune response 1408:1433 Our results suggest that EVs from P. brasiliensis can modulate the innate immune response and affect the relationship between P. brasiliensis and host immune cells. 27775058 7 57 from brasiliensis 1106:1117 arg1 EVs 1094:1096 EVs 1094:1096 EVs from P. brasiliensis 1094:1117 Furthermore, the augmented expression of M2-polarization markers, stimulated by IL-4 plus IL-10, was reverted toward an M1 phenotype in response to secondary stimulation with EVs from P. brasiliensis. 27775058 2 58 theme cargo 235:239 arg1 analysis 241:248 The cargo analysis 231:248 The cargo analysis of EVs 231:255 The cargo analysis of EVs shows that they contain virulence factors suggesting a role in the pathogenesis of infection. 27775058 7 59 theme M2-polarization 960:974 arg1 markers 976:982 M2-polarization markers 960:982 M2-polarization markers 960:982 Furthermore, the augmented expression of M2-polarization markers, stimulated by IL-4 plus IL-10, was reverted toward an M1 phenotype in response to secondary stimulation with EVs from P. brasiliensis. 27775058 8 60 theme yeasts 1300:1305 arg1 recovery 1275:1282 the decreased CFU recovery 1257:1282 the decreased CFU recovery of internalized yeasts 1257:1305 The ability of EVs from P. brasiliensis to promote M1 polarization macrophages favoring an enhanced fungicidal activity, demonstrated by the decreased CFU recovery of internalized yeasts, with comparable phagocytic efficacy. 27775058 6 61 dep markers 881:887 arg1 markers 881:887 the M2 markers Arginase-1, Ym-1, and FIZZ-1 874:916 the M2 markers Arginase-1, Ym-1, and FIZZ-1 874:916 Addition of EV to macrophages also promoted transcription of the M1-polarization marker iNOs and diminish that of the M2 markers Arginase-1, Ym-1, and FIZZ-1. 27775058 6 61 dep markers 881:887 arg1 Ym-1 901:904 Ym-1 901:904 Ym-1 901:904 Addition of EV to macrophages also promoted transcription of the M1-polarization marker iNOs and diminish that of the M2 markers Arginase-1, Ym-1, and FIZZ-1. 27775058 6 61 dep markers 881:887 arg1 FIZZ-1 911:916 FIZZ-1 911:916 FIZZ-1 911:916 Addition of EV to macrophages also promoted transcription of the M1-polarization marker iNOs and diminish that of the M2 markers Arginase-1, Ym-1, and FIZZ-1. 27775058 6 61 dep markers 881:887 arg1 Arginase-1 889:898 Arginase-1 889:898 Arginase-1 889:898 Addition of EV to macrophages also promoted transcription of the M1-polarization marker iNOs and diminish that of the M2 markers Arginase-1, Ym-1, and FIZZ-1. 30023188 4 0 dep agranular 914:922 arg1 smaller 906:912 smaller 906:912 smaller 906:912 The acini I are formed by a large central cell surrounded by several smaller agranular peripheral cells. 30023188 2 1 theme von 684:686 arg1 calcium 675:681 calcium 675:681 calcium (von Kossa technique) 675:703 Unfed individuals were placed on New Zealand White rabbits for feeding and the females, after 4 days, were collected, dissected and the salivary glands were submitted to the application of histological (hematoxylin-eosin technique) and histochemical tests for the detection of protein (bromophenol blue technique, polysaccharides (periodic acid-Schiff technique), lipid (Nile blue technique) and calcium (von Kossa technique). 30023188 2 1 theme von 684:686 arg1 technique 694:702 von Kossa technique 684:702 von Kossa technique 684:702 Unfed individuals were placed on New Zealand White rabbits for feeding and the females, after 4 days, were collected, dissected and the salivary glands were submitted to the application of histological (hematoxylin-eosin technique) and histochemical tests for the detection of protein (bromophenol blue technique, polysaccharides (periodic acid-Schiff technique), lipid (Nile blue technique) and calcium (von Kossa technique). 30023188 1 2 theme semi-engorged 239:251 arg1 females 270:276 semi-engorged Amblyomma triste females 239:276 semi-engorged Amblyomma triste females 239:276 This study presents the morphological and physiological characterization of the salivary glands of semi-engorged Amblyomma triste females. 30023188 2 3 dep protein 556:562 arg1 technique 582:590 bromophenol blue technique 565:590 bromophenol blue technique 565:590 Unfed individuals were placed on New Zealand White rabbits for feeding and the females, after 4 days, were collected, dissected and the salivary glands were submitted to the application of histological (hematoxylin-eosin technique) and histochemical tests for the detection of protein (bromophenol blue technique, polysaccharides (periodic acid-Schiff technique), lipid (Nile blue technique) and calcium (von Kossa technique). 30023188 3 4 theme ducts 789:793 arg1 system 779:784 a system 777:784 a system of ducts and three types of acini (I, II and III) 777:834 The histological results show that the glandular tissue is composed by a system of ducts and three types of acini (I, II and III). 30023188 6 5 theme secretion 1101:1109 arg1 granules 1111:1118 secretion granules 1101:1118 secretion granules 1101:1118 Acini III are constituted by cells d, e and f; the former two contain secretion granules, the latter is agranular. 30023188 0 6 dep Acari 109:113 arg1 Ixodidae 116:123 Ixodidae 116:123 Ixodidae 116:123 Morpho-histochemical characterization of the salivary glands of semi-engorged Amblyomma triste (Koch, 1844) (Acari: Ixodidae) female ticks. 30023188 3 7 theme acini 814:818 arg1 types 805:809 three types 799:809 three types of acini (I, II and III) 799:834 The histological results show that the glandular tissue is composed by a system of ducts and three types of acini (I, II and III). 30023188 3 7 theme acini 814:818 arg1 III 831:833 III 831:833 III 831:833 The histological results show that the glandular tissue is composed by a system of ducts and three types of acini (I, II and III). 30023188 3 7 theme acini 814:818 arg1 II 824:825 II 824:825 II 824:825 The histological results show that the glandular tissue is composed by a system of ducts and three types of acini (I, II and III). 30023188 3 7 theme acini 814:818 arg1 ducts 789:793 ducts 789:793 ducts 789:793 The histological results show that the glandular tissue is composed by a system of ducts and three types of acini (I, II and III). 30023188 1 8 theme Amblyomma 253:261 arg1 females 270:276 semi-engorged Amblyomma triste females 239:276 semi-engorged Amblyomma triste females 239:276 This study presents the morphological and physiological characterization of the salivary glands of semi-engorged Amblyomma triste females. 30023188 8 9 from physiology 1311:1320 arg1 specie 1346:1351 this specie 1341:1351 this specie 1341:1351 Data obtained here will certainly help in the understanding of the cellular morphology and of the general physiology of these organs in this specie, providing important information for the creation of scientific bases which will contribute for the development of more specific and efficient methods of control. 30023188 8 10 theme organs 1331:1336 arg1 physiology 1311:1320 the general physiology 1299:1320 the general physiology of these organs in this specie 1299:1351 Data obtained here will certainly help in the understanding of the cellular morphology and of the general physiology of these organs in this specie, providing important information for the creation of scientific bases which will contribute for the development of more specific and efficient methods of control. 30023188 2 11 theme blue 577:580 arg1 technique 582:590 bromophenol blue technique 565:590 bromophenol blue technique 565:590 Unfed individuals were placed on New Zealand White rabbits for feeding and the females, after 4 days, were collected, dissected and the salivary glands were submitted to the application of histological (hematoxylin-eosin technique) and histochemical tests for the detection of protein (bromophenol blue technique, polysaccharides (periodic acid-Schiff technique), lipid (Nile blue technique) and calcium (von Kossa technique). 30023188 1 12 theme triste 263:268 arg1 females 270:276 semi-engorged Amblyomma triste females 239:276 semi-engorged Amblyomma triste females 239:276 This study presents the morphological and physiological characterization of the salivary glands of semi-engorged Amblyomma triste females. 30023188 4 13 dep acini 841:845 arg1 I 847:847 I 847:847 I 847:847 The acini I are formed by a large central cell surrounded by several smaller agranular peripheral cells. 30023188 2 14 theme bromophenol 565:575 arg1 technique 582:590 bromophenol blue technique 565:590 bromophenol blue technique 565:590 Unfed individuals were placed on New Zealand White rabbits for feeding and the females, after 4 days, were collected, dissected and the salivary glands were submitted to the application of histological (hematoxylin-eosin technique) and histochemical tests for the detection of protein (bromophenol blue technique, polysaccharides (periodic acid-Schiff technique), lipid (Nile blue technique) and calcium (von Kossa technique). 30023188 3 15 dep types 805:809 arg1 III 831:833 III 831:833 III 831:833 The histological results show that the glandular tissue is composed by a system of ducts and three types of acini (I, II and III). 30023188 3 15 dep types 805:809 arg1 types 805:809 three types 799:809 three types of acini (I, II and III) 799:834 The histological results show that the glandular tissue is composed by a system of ducts and three types of acini (I, II and III). 30023188 3 15 dep types 805:809 arg1 II 824:825 II 824:825 II 824:825 The histological results show that the glandular tissue is composed by a system of ducts and three types of acini (I, II and III). 30023188 4 16 theme central 871:877 arg1 cell 879:882 a large central cell 863:882 a large central cell surrounded by several smaller agranular peripheral cells 863:939 The acini I are formed by a large central cell surrounded by several smaller agranular peripheral cells. 30023188 1 17 theme females 270:276 arg1 glands 229:234 the salivary glands 216:234 the salivary glands of semi-engorged Amblyomma triste females 216:276 This study presents the morphological and physiological characterization of the salivary glands of semi-engorged Amblyomma triste females. 30023188 4 18 theme peripheral 924:933 arg1 cells 935:939 several smaller agranular peripheral cells 898:939 several smaller agranular peripheral cells 898:939 The acini I are formed by a large central cell surrounded by several smaller agranular peripheral cells. 30023188 2 19 theme acid-Schiff 619:629 arg1 technique 631:639 periodic acid-Schiff technique 610:639 periodic acid-Schiff technique 610:639 Unfed individuals were placed on New Zealand White rabbits for feeding and the females, after 4 days, were collected, dissected and the salivary glands were submitted to the application of histological (hematoxylin-eosin technique) and histochemical tests for the detection of protein (bromophenol blue technique, polysaccharides (periodic acid-Schiff technique), lipid (Nile blue technique) and calcium (von Kossa technique). 30023188 2 19 theme acid-Schiff 619:629 arg1 polysaccharides 593:607 polysaccharides 593:607 polysaccharides (periodic acid-Schiff technique) 593:640 Unfed individuals were placed on New Zealand White rabbits for feeding and the females, after 4 days, were collected, dissected and the salivary glands were submitted to the application of histological (hematoxylin-eosin technique) and histochemical tests for the detection of protein (bromophenol blue technique, polysaccharides (periodic acid-Schiff technique), lipid (Nile blue technique) and calcium (von Kossa technique). 30023188 2 20 theme Unfed 279:283 arg1 individuals 285:295 Unfed individuals 279:295 Unfed individuals 279:295 Unfed individuals were placed on New Zealand White rabbits for feeding and the females, after 4 days, were collected, dissected and the salivary glands were submitted to the application of histological (hematoxylin-eosin technique) and histochemical tests for the detection of protein (bromophenol blue technique, polysaccharides (periodic acid-Schiff technique), lipid (Nile blue technique) and calcium (von Kossa technique). 30023188 6 21 contain contain 1093:1099 arg2 granules 1111:1118 secretion granules 1101:1118 secretion granules 1101:1118 Acini III are constituted by cells d, e and f; the former two contain secretion granules, the latter is agranular. 30023188 6 21 contain contain 1093:1099 arg1 two 1089:1091 two 1089:1091 two 1089:1091 Acini III are constituted by cells d, e and f; the former two contain secretion granules, the latter is agranular. 30023188 2 22 theme hematoxylin-eosin 482:498 arg1 technique 500:508 hematoxylin-eosin technique 482:508 hematoxylin-eosin technique 482:508 Unfed individuals were placed on New Zealand White rabbits for feeding and the females, after 4 days, were collected, dissected and the salivary glands were submitted to the application of histological (hematoxylin-eosin technique) and histochemical tests for the detection of protein (bromophenol blue technique, polysaccharides (periodic acid-Schiff technique), lipid (Nile blue technique) and calcium (von Kossa technique). 30023188 2 23 theme periodic 610:617 arg1 acid-Schiff 619:629 periodic acid-Schiff 610:629 periodic acid-Schiff technique 610:639 Unfed individuals were placed on New Zealand White rabbits for feeding and the females, after 4 days, were collected, dissected and the salivary glands were submitted to the application of histological (hematoxylin-eosin technique) and histochemical tests for the detection of protein (bromophenol blue technique, polysaccharides (periodic acid-Schiff technique), lipid (Nile blue technique) and calcium (von Kossa technique). 30023188 2 24 theme salivary 415:422 arg1 glands 424:429 the salivary glands 411:429 the salivary glands 411:429 Unfed individuals were placed on New Zealand White rabbits for feeding and the females, after 4 days, were collected, dissected and the salivary glands were submitted to the application of histological (hematoxylin-eosin technique) and histochemical tests for the detection of protein (bromophenol blue technique, polysaccharides (periodic acid-Schiff technique), lipid (Nile blue technique) and calcium (von Kossa technique). 30023188 7 25 theme glandular 1150:1158 arg1 composition 1174:1184 The glandular histochemical composition 1146:1184 The glandular histochemical composition 1146:1184 The glandular histochemical composition was also verified. 30023188 2 26 theme blue 655:658 arg1 lipid 643:647 lipid 643:647 lipid (Nile blue technique) 643:669 Unfed individuals were placed on New Zealand White rabbits for feeding and the females, after 4 days, were collected, dissected and the salivary glands were submitted to the application of histological (hematoxylin-eosin technique) and histochemical tests for the detection of protein (bromophenol blue technique, polysaccharides (periodic acid-Schiff technique), lipid (Nile blue technique) and calcium (von Kossa technique). 30023188 2 26 theme blue 655:658 arg1 technique 660:668 Nile blue technique 650:668 Nile blue technique 650:668 Unfed individuals were placed on New Zealand White rabbits for feeding and the females, after 4 days, were collected, dissected and the salivary glands were submitted to the application of histological (hematoxylin-eosin technique) and histochemical tests for the detection of protein (bromophenol blue technique, polysaccharides (periodic acid-Schiff technique), lipid (Nile blue technique) and calcium (von Kossa technique). 30023188 2 27 theme Zealand 316:322 arg1 rabbits 330:336 New Zealand White rabbits 312:336 New Zealand White rabbits for feeding 312:348 Unfed individuals were placed on New Zealand White rabbits for feeding and the females, after 4 days, were collected, dissected and the salivary glands were submitted to the application of histological (hematoxylin-eosin technique) and histochemical tests for the detection of protein (bromophenol blue technique, polysaccharides (periodic acid-Schiff technique), lipid (Nile blue technique) and calcium (von Kossa technique). 30023188 2 28 theme protein 556:562 arg1 detection 543:551 the detection 539:551 the detection of protein (bromophenol blue technique, polysaccharides (periodic acid-Schiff technique), lipid (Nile blue technique) and calcium (von Kossa technique) 539:703 Unfed individuals were placed on New Zealand White rabbits for feeding and the females, after 4 days, were collected, dissected and the salivary glands were submitted to the application of histological (hematoxylin-eosin technique) and histochemical tests for the detection of protein (bromophenol blue technique, polysaccharides (periodic acid-Schiff technique), lipid (Nile blue technique) and calcium (von Kossa technique). 30023188 0 29 theme Morpho-histochemical 0:19 arg1 characterization 21:36 Morpho-histochemical characterization 0:36 Morpho-histochemical characterization of the salivary glands of semi-engorged Amblyomma triste (Koch, 1844) (Acari: Ixodidae) female ticks. 0:138 Morpho-histochemical characterization of the salivary glands of semi-engorged Amblyomma triste (Koch, 1844) (Acari: Ixodidae) female ticks. 30023188 3 30 theme histological 710:721 arg1 results 723:729 The histological results 706:729 The histological results 706:729 The histological results show that the glandular tissue is composed by a system of ducts and three types of acini (I, II and III). 30023188 2 31 theme Nile 650:653 arg1 lipid 643:647 lipid 643:647 lipid (Nile blue technique) 643:669 Unfed individuals were placed on New Zealand White rabbits for feeding and the females, after 4 days, were collected, dissected and the salivary glands were submitted to the application of histological (hematoxylin-eosin technique) and histochemical tests for the detection of protein (bromophenol blue technique, polysaccharides (periodic acid-Schiff technique), lipid (Nile blue technique) and calcium (von Kossa technique). 30023188 2 31 theme Nile 650:653 arg1 technique 660:668 Nile blue technique 650:668 Nile blue technique 650:668 Unfed individuals were placed on New Zealand White rabbits for feeding and the females, after 4 days, were collected, dissected and the salivary glands were submitted to the application of histological (hematoxylin-eosin technique) and histochemical tests for the detection of protein (bromophenol blue technique, polysaccharides (periodic acid-Schiff technique), lipid (Nile blue technique) and calcium (von Kossa technique). 30023188 2 32 theme New 312:314 arg1 rabbits 330:336 New Zealand White rabbits 312:336 New Zealand White rabbits for feeding 312:348 Unfed individuals were placed on New Zealand White rabbits for feeding and the females, after 4 days, were collected, dissected and the salivary glands were submitted to the application of histological (hematoxylin-eosin technique) and histochemical tests for the detection of protein (bromophenol blue technique, polysaccharides (periodic acid-Schiff technique), lipid (Nile blue technique) and calcium (von Kossa technique). 30023188 1 33 theme morphological 164:176 arg1 characterization 196:211 the morphological and physiological characterization 160:211 the morphological and physiological characterization of the salivary glands of semi-engorged Amblyomma triste females 160:276 This study presents the morphological and physiological characterization of the salivary glands of semi-engorged Amblyomma triste females. 30023188 8 34 theme important 1364:1372 arg1 information 1374:1384 important information 1364:1384 important information 1364:1384 Data obtained here will certainly help in the understanding of the cellular morphology and of the general physiology of these organs in this specie, providing important information for the creation of scientific bases which will contribute for the development of more specific and efficient methods of control. 30023188 8 35 theme morphology 1281:1290 arg1 understanding 1251:1263 the understanding 1247:1263 the understanding of the cellular morphology and of the general physiology of these organs in this specie 1247:1351 Data obtained here will certainly help in the understanding of the cellular morphology and of the general physiology of these organs in this specie, providing important information for the creation of scientific bases which will contribute for the development of more specific and efficient methods of control. 30023188 0 36 dep triste 88:93 arg1 Acari 109:113 Acari 109:113 Acari 109:113 Morpho-histochemical characterization of the salivary glands of semi-engorged Amblyomma triste (Koch, 1844) (Acari: Ixodidae) female ticks. 30023188 0 36 dep triste 88:93 arg1 Koch 96:99 Koch 96:99 Koch 96:99 Morpho-histochemical characterization of the salivary glands of semi-engorged Amblyomma triste (Koch, 1844) (Acari: Ixodidae) female ticks. 30023188 8 37 from understanding 1251:1263 arg1 specie 1346:1351 this specie 1341:1351 this specie 1341:1351 Data obtained here will certainly help in the understanding of the cellular morphology and of the general physiology of these organs in this specie, providing important information for the creation of scientific bases which will contribute for the development of more specific and efficient methods of control. 30023188 8 38 theme cellular 1272:1279 arg1 morphology 1281:1290 the cellular morphology 1268:1290 the cellular morphology 1268:1290 Data obtained here will certainly help in the understanding of the cellular morphology and of the general physiology of these organs in this specie, providing important information for the creation of scientific bases which will contribute for the development of more specific and efficient methods of control. 30023188 1 39 theme physiological 182:194 arg1 characterization 196:211 the morphological and physiological characterization 160:211 the morphological and physiological characterization of the salivary glands of semi-engorged Amblyomma triste females 160:276 This study presents the morphological and physiological characterization of the salivary glands of semi-engorged Amblyomma triste females. 30023188 0 40 theme glands 54:59 arg1 characterization 21:36 Morpho-histochemical characterization 0:36 Morpho-histochemical characterization of the salivary glands of semi-engorged Amblyomma triste (Koch, 1844) (Acari: Ixodidae) female ticks. 0:138 Morpho-histochemical characterization of the salivary glands of semi-engorged Amblyomma triste (Koch, 1844) (Acari: Ixodidae) female ticks. 30023188 2 41 theme tests 529:533 arg1 application 453:463 the application 449:463 the application of histological (hematoxylin-eosin technique) and histochemical tests for the detection of protein (bromophenol blue technique, polysaccharides (periodic acid-Schiff technique), lipid (Nile blue technique) and calcium (von Kossa technique) 449:703 Unfed individuals were placed on New Zealand White rabbits for feeding and the females, after 4 days, were collected, dissected and the salivary glands were submitted to the application of histological (hematoxylin-eosin technique) and histochemical tests for the detection of protein (bromophenol blue technique, polysaccharides (periodic acid-Schiff technique), lipid (Nile blue technique) and calcium (von Kossa technique). 30023188 4 42 theme agranular 914:922 arg1 cells 935:939 several smaller agranular peripheral cells 898:939 several smaller agranular peripheral cells 898:939 The acini I are formed by a large central cell surrounded by several smaller agranular peripheral cells. 30023188 8 43 theme efficient 1486:1494 arg1 methods 1496:1502 more specific and efficient methods 1468:1502 more specific and efficient methods of control 1468:1513 Data obtained here will certainly help in the understanding of the cellular morphology and of the general physiology of these organs in this specie, providing important information for the creation of scientific bases which will contribute for the development of more specific and efficient methods of control. 30023188 0 44 theme salivary 45:52 arg1 glands 54:59 the salivary glands 41:59 the salivary glands of semi-engorged Amblyomma triste (Koch, 1844) (Acari: Ixodidae) female ticks 41:137 Morpho-histochemical characterization of the salivary glands of semi-engorged Amblyomma triste (Koch, 1844) (Acari: Ixodidae) female ticks. 30023188 2 45 theme histochemical 515:527 arg1 tests 529:533 histological (hematoxylin-eosin technique) and histochemical tests 468:533 histological (hematoxylin-eosin technique) and histochemical tests for the detection of protein (bromophenol blue technique, polysaccharides (periodic acid-Schiff technique), lipid (Nile blue technique) and calcium (von Kossa technique) 468:703 Unfed individuals were placed on New Zealand White rabbits for feeding and the females, after 4 days, were collected, dissected and the salivary glands were submitted to the application of histological (hematoxylin-eosin technique) and histochemical tests for the detection of protein (bromophenol blue technique, polysaccharides (periodic acid-Schiff technique), lipid (Nile blue technique) and calcium (von Kossa technique). 30023188 5 46 dep cells 965:969 arg1 a 971:971 a 971:971 a 971:971 Acini II are formed by cells a, c1, c2, c3 and c5, which are full of secretion granules. 30023188 8 47 theme scientific 1406:1415 arg1 bases 1417:1421 scientific bases 1406:1421 scientific bases which will contribute for the development of more specific and efficient methods of control 1406:1513 Data obtained here will certainly help in the understanding of the cellular morphology and of the general physiology of these organs in this specie, providing important information for the creation of scientific bases which will contribute for the development of more specific and efficient methods of control. 30023188 0 48 theme semi-engorged 64:76 arg1 triste 88:93 semi-engorged Amblyomma triste 64:93 semi-engorged Amblyomma triste (Koch, 1844) (Acari: Ixodidae) female ticks 64:137 Morpho-histochemical characterization of the salivary glands of semi-engorged Amblyomma triste (Koch, 1844) (Acari: Ixodidae) female ticks. 30023188 3 49 theme glandular 745:753 arg1 tissue 755:760 the glandular tissue 741:760 the glandular tissue 741:760 The histological results show that the glandular tissue is composed by a system of ducts and three types of acini (I, II and III). 30023188 0 50 theme ticks 133:137 arg1 glands 54:59 the salivary glands 41:59 the salivary glands of semi-engorged Amblyomma triste (Koch, 1844) (Acari: Ixodidae) female ticks 41:137 Morpho-histochemical characterization of the salivary glands of semi-engorged Amblyomma triste (Koch, 1844) (Acari: Ixodidae) female ticks. 30023188 2 51 theme histological 468:479 arg1 tests 529:533 histological (hematoxylin-eosin technique) and histochemical tests 468:533 histological (hematoxylin-eosin technique) and histochemical tests for the detection of protein (bromophenol blue technique, polysaccharides (periodic acid-Schiff technique), lipid (Nile blue technique) and calcium (von Kossa technique) 468:703 Unfed individuals were placed on New Zealand White rabbits for feeding and the females, after 4 days, were collected, dissected and the salivary glands were submitted to the application of histological (hematoxylin-eosin technique) and histochemical tests for the detection of protein (bromophenol blue technique, polysaccharides (periodic acid-Schiff technique), lipid (Nile blue technique) and calcium (von Kossa technique). 30023188 2 52 dep technique 582:590 arg1 technique 631:639 periodic acid-Schiff technique 610:639 periodic acid-Schiff technique 610:639 Unfed individuals were placed on New Zealand White rabbits for feeding and the females, after 4 days, were collected, dissected and the salivary glands were submitted to the application of histological (hematoxylin-eosin technique) and histochemical tests for the detection of protein (bromophenol blue technique, polysaccharides (periodic acid-Schiff technique), lipid (Nile blue technique) and calcium (von Kossa technique). 30023188 2 52 dep technique 582:590 arg1 technique 694:702 von Kossa technique 684:702 von Kossa technique 684:702 Unfed individuals were placed on New Zealand White rabbits for feeding and the females, after 4 days, were collected, dissected and the salivary glands were submitted to the application of histological (hematoxylin-eosin technique) and histochemical tests for the detection of protein (bromophenol blue technique, polysaccharides (periodic acid-Schiff technique), lipid (Nile blue technique) and calcium (von Kossa technique). 30023188 2 52 dep technique 582:590 arg1 lipid 643:647 lipid 643:647 lipid (Nile blue technique) 643:669 Unfed individuals were placed on New Zealand White rabbits for feeding and the females, after 4 days, were collected, dissected and the salivary glands were submitted to the application of histological (hematoxylin-eosin technique) and histochemical tests for the detection of protein (bromophenol blue technique, polysaccharides (periodic acid-Schiff technique), lipid (Nile blue technique) and calcium (von Kossa technique). 30023188 2 52 dep technique 582:590 arg1 polysaccharides 593:607 polysaccharides 593:607 polysaccharides (periodic acid-Schiff technique) 593:640 Unfed individuals were placed on New Zealand White rabbits for feeding and the females, after 4 days, were collected, dissected and the salivary glands were submitted to the application of histological (hematoxylin-eosin technique) and histochemical tests for the detection of protein (bromophenol blue technique, polysaccharides (periodic acid-Schiff technique), lipid (Nile blue technique) and calcium (von Kossa technique). 30023188 2 52 dep technique 582:590 arg1 calcium 675:681 calcium 675:681 calcium (von Kossa technique) 675:703 Unfed individuals were placed on New Zealand White rabbits for feeding and the females, after 4 days, were collected, dissected and the salivary glands were submitted to the application of histological (hematoxylin-eosin technique) and histochemical tests for the detection of protein (bromophenol blue technique, polysaccharides (periodic acid-Schiff technique), lipid (Nile blue technique) and calcium (von Kossa technique). 30023188 2 52 dep technique 582:590 arg1 technique 660:668 Nile blue technique 650:668 Nile blue technique 650:668 Unfed individuals were placed on New Zealand White rabbits for feeding and the females, after 4 days, were collected, dissected and the salivary glands were submitted to the application of histological (hematoxylin-eosin technique) and histochemical tests for the detection of protein (bromophenol blue technique, polysaccharides (periodic acid-Schiff technique), lipid (Nile blue technique) and calcium (von Kossa technique). 30023188 8 53 theme bases 1417:1421 arg1 creation 1394:1401 the creation 1390:1401 the creation of scientific bases which will contribute for the development of more specific and efficient methods of control 1390:1513 Data obtained here will certainly help in the understanding of the cellular morphology and of the general physiology of these organs in this specie, providing important information for the creation of scientific bases which will contribute for the development of more specific and efficient methods of control. 30023188 0 54 theme female 126:131 arg1 ticks 133:137 semi-engorged Amblyomma triste (Koch, 1844) (Acari: Ixodidae) female ticks 64:137 semi-engorged Amblyomma triste (Koch, 1844) (Acari: Ixodidae) female ticks 64:137 Morpho-histochemical characterization of the salivary glands of semi-engorged Amblyomma triste (Koch, 1844) (Acari: Ixodidae) female ticks. 30023188 4 55 theme large 865:869 arg1 cell 879:882 a large central cell 863:882 a large central cell surrounded by several smaller agranular peripheral cells 863:939 The acini I are formed by a large central cell surrounded by several smaller agranular peripheral cells. 30023188 2 56 dep placed 302:307 arg1 collected 386:394 collected 386:394 were collected 381:394 Unfed individuals were placed on New Zealand White rabbits for feeding and the females, after 4 days, were collected, dissected and the salivary glands were submitted to the application of histological (hematoxylin-eosin technique) and histochemical tests for the detection of protein (bromophenol blue technique, polysaccharides (periodic acid-Schiff technique), lipid (Nile blue technique) and calcium (von Kossa technique). 30023188 2 56 dep placed 302:307 arg1 dissected 397:405 dissected 397:405 dissected 397:405 Unfed individuals were placed on New Zealand White rabbits for feeding and the females, after 4 days, were collected, dissected and the salivary glands were submitted to the application of histological (hematoxylin-eosin technique) and histochemical tests for the detection of protein (bromophenol blue technique, polysaccharides (periodic acid-Schiff technique), lipid (Nile blue technique) and calcium (von Kossa technique). 30023188 3 57 theme types 805:809 arg1 system 779:784 a system 777:784 a system of ducts and three types of acini (I, II and III) 777:834 The histological results show that the glandular tissue is composed by a system of ducts and three types of acini (I, II and III). 30023188 5 58 theme secretion 1011:1019 arg1 granules 1021:1028 secretion granules 1011:1028 secretion granules 1011:1028 Acini II are formed by cells a, c1, c2, c3 and c5, which are full of secretion granules. 30023188 6 59 dep cells 1060:1064 arg1 f 1075:1075 f 1075:1075 f 1075:1075 Acini III are constituted by cells d, e and f; the former two contain secretion granules, the latter is agranular. 30023188 6 59 dep cells 1060:1064 arg1 cells 1060:1064 cells d, e and f 1060:1075 cells d, e and f 1060:1075 Acini III are constituted by cells d, e and f; the former two contain secretion granules, the latter is agranular. 30023188 6 59 dep cells 1060:1064 arg1 e 1069:1069 e 1069:1069 e 1069:1069 Acini III are constituted by cells d, e and f; the former two contain secretion granules, the latter is agranular. 30023188 6 59 dep cells 1060:1064 arg1 d 1066:1066 d 1066:1066 d 1066:1066 Acini III are constituted by cells d, e and f; the former two contain secretion granules, the latter is agranular. 30023188 8 60 theme specific 1473:1480 arg1 methods 1496:1502 more specific and efficient methods 1468:1502 more specific and efficient methods of control 1468:1513 Data obtained here will certainly help in the understanding of the cellular morphology and of the general physiology of these organs in this specie, providing important information for the creation of scientific bases which will contribute for the development of more specific and efficient methods of control. 30023188 2 61 dep histological 468:479 arg1 technique 500:508 hematoxylin-eosin technique 482:508 hematoxylin-eosin technique 482:508 Unfed individuals were placed on New Zealand White rabbits for feeding and the females, after 4 days, were collected, dissected and the salivary glands were submitted to the application of histological (hematoxylin-eosin technique) and histochemical tests for the detection of protein (bromophenol blue technique, polysaccharides (periodic acid-Schiff technique), lipid (Nile blue technique) and calcium (von Kossa technique). 30023188 8 62 theme physiology 1311:1320 arg1 understanding 1251:1263 the understanding 1247:1263 the understanding of the cellular morphology and of the general physiology of these organs in this specie 1247:1351 Data obtained here will certainly help in the understanding of the cellular morphology and of the general physiology of these organs in this specie, providing important information for the creation of scientific bases which will contribute for the development of more specific and efficient methods of control. 30023188 2 63 theme White 324:328 arg1 rabbits 330:336 New Zealand White rabbits 312:336 New Zealand White rabbits for feeding 312:348 Unfed individuals were placed on New Zealand White rabbits for feeding and the females, after 4 days, were collected, dissected and the salivary glands were submitted to the application of histological (hematoxylin-eosin technique) and histochemical tests for the detection of protein (bromophenol blue technique, polysaccharides (periodic acid-Schiff technique), lipid (Nile blue technique) and calcium (von Kossa technique). 30023188 8 64 theme methods 1496:1502 arg1 development 1453:1463 the development 1449:1463 the development of more specific and efficient methods of control 1449:1513 Data obtained here will certainly help in the understanding of the cellular morphology and of the general physiology of these organs in this specie, providing important information for the creation of scientific bases which will contribute for the development of more specific and efficient methods of control. 30023188 1 65 theme salivary 220:227 arg1 glands 229:234 the salivary glands 216:234 the salivary glands of semi-engorged Amblyomma triste females 216:276 This study presents the morphological and physiological characterization of the salivary glands of semi-engorged Amblyomma triste females. 30023188 0 66 theme triste 88:93 arg1 ticks 133:137 semi-engorged Amblyomma triste (Koch, 1844) (Acari: Ixodidae) female ticks 64:137 semi-engorged Amblyomma triste (Koch, 1844) (Acari: Ixodidae) female ticks 64:137 Morpho-histochemical characterization of the salivary glands of semi-engorged Amblyomma triste (Koch, 1844) (Acari: Ixodidae) female ticks. 30023188 8 67 theme general 1303:1309 arg1 physiology 1311:1320 the general physiology 1299:1320 the general physiology of these organs in this specie 1299:1351 Data obtained here will certainly help in the understanding of the cellular morphology and of the general physiology of these organs in this specie, providing important information for the creation of scientific bases which will contribute for the development of more specific and efficient methods of control. 30023188 7 68 theme histochemical 1160:1172 arg1 composition 1174:1184 The glandular histochemical composition 1146:1184 The glandular histochemical composition 1146:1184 The glandular histochemical composition was also verified. 30023188 5 69 theme granules 1021:1028 arg1 full 1003:1006 full 1003:1006 full 1003:1006 Acini II are formed by cells a, c1, c2, c3 and c5, which are full of secretion granules. 30023188 1 70 theme glands 229:234 arg1 characterization 196:211 the morphological and physiological characterization 160:211 the morphological and physiological characterization of the salivary glands of semi-engorged Amblyomma triste females 160:276 This study presents the morphological and physiological characterization of the salivary glands of semi-engorged Amblyomma triste females. 30023188 0 71 theme Amblyomma 78:86 arg1 triste 88:93 semi-engorged Amblyomma triste 64:93 semi-engorged Amblyomma triste (Koch, 1844) (Acari: Ixodidae) female ticks 64:137 Morpho-histochemical characterization of the salivary glands of semi-engorged Amblyomma triste (Koch, 1844) (Acari: Ixodidae) female ticks. 30023188 2 72 theme Kossa 688:692 arg1 calcium 675:681 calcium 675:681 calcium (von Kossa technique) 675:703 Unfed individuals were placed on New Zealand White rabbits for feeding and the females, after 4 days, were collected, dissected and the salivary glands were submitted to the application of histological (hematoxylin-eosin technique) and histochemical tests for the detection of protein (bromophenol blue technique, polysaccharides (periodic acid-Schiff technique), lipid (Nile blue technique) and calcium (von Kossa technique). 30023188 2 72 theme Kossa 688:692 arg1 technique 694:702 von Kossa technique 684:702 von Kossa technique 684:702 Unfed individuals were placed on New Zealand White rabbits for feeding and the females, after 4 days, were collected, dissected and the salivary glands were submitted to the application of histological (hematoxylin-eosin technique) and histochemical tests for the detection of protein (bromophenol blue technique, polysaccharides (periodic acid-Schiff technique), lipid (Nile blue technique) and calcium (von Kossa technique). 30023188 8 73 theme control 1507:1513 arg1 methods 1496:1502 more specific and efficient methods 1468:1502 more specific and efficient methods of control 1468:1513 Data obtained here will certainly help in the understanding of the cellular morphology and of the general physiology of these organs in this specie, providing important information for the creation of scientific bases which will contribute for the development of more specific and efficient methods of control. 30023188 8 74 from specie 1346:1351 arg1 understanding 1251:1263 the understanding 1247:1263 the understanding of the cellular morphology and of the general physiology of these organs in this specie 1247:1351 Data obtained here will certainly help in the understanding of the cellular morphology and of the general physiology of these organs in this specie, providing important information for the creation of scientific bases which will contribute for the development of more specific and efficient methods of control. 30011702 0 0 theme fat 82:84 arg1 replacers 86:94 fat replacers 82:94 fat replacers 82:94 Reduced calorie emulsion-based foods: Protein microparticles and dietary fiber as fat replacers. 30011702 3 1 theme protein 633:639 arg1 aggregates 641:650 large protein aggregates 627:650 large protein aggregates 627:650 Increasing protein concentration (2.5-7.5%) increased the mean (d3,2) particle diameter due to the formation of large protein aggregates. 30011702 8 2 theme mixed 1172:1176 arg1 systems 1178:1184 the mixed systems 1168:1184 the mixed systems 1168:1184 Overall, the appearance and rheological properties of the mixed systems were similar to commercial sauces and dressings. 30011702 9 3 theme calorie 1272:1278 arg1 emulsions 1285:1293 reduced calorie food emulsions 1264:1293 reduced calorie food emulsions with appearance and consistency similar to those of full-fat versions 1264:1363 This study demonstrates that reduced calorie food emulsions with appearance and consistency similar to those of full-fat versions can be formulated using protein microparticles and polysaccharides. 30011702 7 4 theme calcium 989:995 arg1 10mM 1007:1010 10mM 1007:1010 10mM 1007:1010 Addition of calcium chloride (10mM) and pH adjustment (2-8) caused little change in the physicochemical properties of the mixed systems. 30011702 7 4 theme calcium 989:995 arg1 chloride 997:1004 calcium chloride 989:1004 calcium chloride (10mM) 989:1011 Addition of calcium chloride (10mM) and pH adjustment (2-8) caused little change in the physicochemical properties of the mixed systems. 30011702 9 5 theme protein 1389:1395 arg1 microparticles 1397:1410 protein microparticles 1389:1410 protein microparticles 1389:1410 This study demonstrates that reduced calorie food emulsions with appearance and consistency similar to those of full-fat versions can be formulated using protein microparticles and polysaccharides. 30011702 6 6 theme LBG 865:867 arg1 Addition 845:852 Addition 845:852 Addition of starch, LBG, or MWP 845:875 Addition of starch, LBG, or MWP increased emulsion viscosity due to the increased effective volume fraction of the dispersed phase. 30011702 2 7 theme emulsions 474:482 arg1 properties 434:443 the properties 430:443 the properties of thermally processed model emulsions (90°C/10min) 430:495 The influence of food matrix composition (protein, polysaccharide, and fat content), ionic strength, and pH on the properties of thermally processed model emulsions (90°C/10min) was investigated. 30011702 3 8 theme mean 573:576 arg1 diameter 594:601 the mean (d3,2) particle diameter 569:601 the mean (d3,2) particle diameter 569:601 Increasing protein concentration (2.5-7.5%) increased the mean (d3,2) particle diameter due to the formation of large protein aggregates. 30011702 1 9 theme fat 228:230 arg1 protein 143:149 microparticulated whey protein 120:149 microparticulated whey protein (MWP) in combination with either modified starch or locust bean gum (LBG) 120:223 The potential of using microparticulated whey protein (MWP) in combination with either modified starch or locust bean gum (LBG) as fat mimetics to fabricate reduced calorie emulsion-based sauces and dressings was studied. 30011702 1 9 theme fat 228:230 arg1 mimetics 232:239 fat mimetics 228:239 fat mimetics 228:239 The potential of using microparticulated whey protein (MWP) in combination with either modified starch or locust bean gum (LBG) as fat mimetics to fabricate reduced calorie emulsion-based sauces and dressings was studied. 30011702 2 10 theme model 468:472 arg1 90°C/10min 485:494 90°C/10min 485:494 90°C/10min 485:494 The influence of food matrix composition (protein, polysaccharide, and fat content), ionic strength, and pH on the properties of thermally processed model emulsions (90°C/10min) was investigated. 30011702 2 10 theme model 468:472 arg1 emulsions 474:482 thermally processed model emulsions 448:482 thermally processed model emulsions (90°C/10min) 448:495 The influence of food matrix composition (protein, polysaccharide, and fat content), ionic strength, and pH on the properties of thermally processed model emulsions (90°C/10min) was investigated. 30011702 8 11 theme systems 1178:1184 arg1 appearance 1127:1136 appearance 1127:1136 appearance 1127:1136 Overall, the appearance and rheological properties of the mixed systems were similar to commercial sauces and dressings. 30011702 8 11 theme systems 1178:1184 arg1 properties 1154:1163 rheological properties 1142:1163 rheological properties 1142:1163 Overall, the appearance and rheological properties of the mixed systems were similar to commercial sauces and dressings. 30011702 1 12 from protein 143:149 arg1 combination 160:170 combination 160:170 combination with either modified starch or locust bean gum (LBG) 160:223 The potential of using microparticulated whey protein (MWP) in combination with either modified starch or locust bean gum (LBG) as fat mimetics to fabricate reduced calorie emulsion-based sauces and dressings was studied. 30011702 4 13 theme white 693:697 arg1 appearance 699:708 a creamy white appearance 684:708 a creamy white appearance 684:708 All MWP-containing systems had a creamy white appearance with high lightness (L*>75). 30011702 6 14 theme starch 857:862 arg1 Addition 845:852 Addition 845:852 Addition of starch, LBG, or MWP 845:875 Addition of starch, LBG, or MWP increased emulsion viscosity due to the increased effective volume fraction of the dispersed phase. 30011702 2 15 theme processed 458:466 arg1 90°C/10min 485:494 90°C/10min 485:494 90°C/10min 485:494 The influence of food matrix composition (protein, polysaccharide, and fat content), ionic strength, and pH on the properties of thermally processed model emulsions (90°C/10min) was investigated. 30011702 2 15 theme processed 458:466 arg1 emulsions 474:482 thermally processed model emulsions 448:482 thermally processed model emulsions (90°C/10min) 448:495 The influence of food matrix composition (protein, polysaccharide, and fat content), ionic strength, and pH on the properties of thermally processed model emulsions (90°C/10min) was investigated. 30011702 7 16 theme pH 1017:1018 arg1 2-8 1032:1034 2-8 1032:1034 2-8 1032:1034 Addition of calcium chloride (10mM) and pH adjustment (2-8) caused little change in the physicochemical properties of the mixed systems. 30011702 7 16 theme pH 1017:1018 arg1 adjustment 1020:1029 pH adjustment 1017:1029 pH adjustment (2-8) 1017:1035 Addition of calcium chloride (10mM) and pH adjustment (2-8) caused little change in the physicochemical properties of the mixed systems. 30011702 9 17 theme similar 1327:1333 arg1 appearance 1300:1309 appearance 1300:1309 appearance 1300:1309 This study demonstrates that reduced calorie food emulsions with appearance and consistency similar to those of full-fat versions can be formulated using protein microparticles and polysaccharides. 30011702 4 18 theme high 715:718 arg1 lightness 720:728 high lightness 715:728 high lightness (L*>75) 715:736 All MWP-containing systems had a creamy white appearance with high lightness (L*>75). 30011702 4 18 theme high 715:718 arg1 * 732:732 L*>75 731:735 L*>75 731:735 All MWP-containing systems had a creamy white appearance with high lightness (L*>75). 30011702 9 19 theme food 1280:1283 arg1 emulsions 1285:1293 reduced calorie food emulsions 1264:1293 reduced calorie food emulsions with appearance and consistency similar to those of full-fat versions 1264:1363 This study demonstrates that reduced calorie food emulsions with appearance and consistency similar to those of full-fat versions can be formulated using protein microparticles and polysaccharides. 30011702 3 20 theme aggregates 641:650 arg1 formation 614:622 the formation 610:622 the formation of large protein aggregates 610:650 Increasing protein concentration (2.5-7.5%) increased the mean (d3,2) particle diameter due to the formation of large protein aggregates. 30011702 0 21 theme Protein 38:44 arg1 microparticles 46:59 emulsion-based foods: Protein microparticles 16:59 emulsion-based foods: Protein microparticles 16:59 Reduced calorie emulsion-based foods: Protein microparticles and dietary fiber as fat replacers. 30011702 6 22 theme volume 937:942 arg1 fraction 944:951 the increased effective volume fraction 913:951 the increased effective volume fraction of the dispersed phase 913:974 Addition of starch, LBG, or MWP increased emulsion viscosity due to the increased effective volume fraction of the dispersed phase. 30011702 2 23 theme ionic 404:408 arg1 strength 410:417 ionic strength 404:417 ionic strength 404:417 The influence of food matrix composition (protein, polysaccharide, and fat content), ionic strength, and pH on the properties of thermally processed model emulsions (90°C/10min) was investigated. 30011702 4 24 contain had 680:682 arg1 systems 672:678 All MWP-containing systems 653:678 All MWP-containing systems 653:678 All MWP-containing systems had a creamy white appearance with high lightness (L*>75). 30011702 4 24 contain had 680:682 arg2 appearance 699:708 a creamy white appearance 684:708 a creamy white appearance 684:708 All MWP-containing systems had a creamy white appearance with high lightness (L*>75). 30011702 2 25 from influence 323:331 arg1 properties 434:443 the properties 430:443 the properties of thermally processed model emulsions (90°C/10min) 430:495 The influence of food matrix composition (protein, polysaccharide, and fat content), ionic strength, and pH on the properties of thermally processed model emulsions (90°C/10min) was investigated. 30011702 3 26 theme Increasing 515:524 arg1 concentration 534:546 Increasing protein concentration 515:546 Increasing protein concentration (2.5-7.5%) 515:557 Increasing protein concentration (2.5-7.5%) increased the mean (d3,2) particle diameter due to the formation of large protein aggregates. 30011702 3 26 theme Increasing 515:524 arg1 % 556:556 2.5-7.5% 549:556 2.5-7.5% 549:556 Increasing protein concentration (2.5-7.5%) increased the mean (d3,2) particle diameter due to the formation of large protein aggregates. 30011702 7 27 theme adjustment 1020:1029 arg1 Addition 977:984 Addition 977:984 Addition of calcium chloride (10mM) and pH adjustment (2-8) 977:1035 Addition of calcium chloride (10mM) and pH adjustment (2-8) caused little change in the physicochemical properties of the mixed systems. 30011702 6 28 theme effective 927:935 arg1 fraction 944:951 the increased effective volume fraction 913:951 the increased effective volume fraction of the dispersed phase 913:974 Addition of starch, LBG, or MWP increased emulsion viscosity due to the increased effective volume fraction of the dispersed phase. 30011702 3 29 theme protein 526:532 arg1 concentration 534:546 Increasing protein concentration 515:546 Increasing protein concentration (2.5-7.5%) 515:557 Increasing protein concentration (2.5-7.5%) increased the mean (d3,2) particle diameter due to the formation of large protein aggregates. 30011702 3 29 theme protein 526:532 arg1 % 556:556 2.5-7.5% 549:556 2.5-7.5% 549:556 Increasing protein concentration (2.5-7.5%) increased the mean (d3,2) particle diameter due to the formation of large protein aggregates. 30011702 2 30 theme composition 348:358 arg1 influence 323:331 The influence 319:331 The influence of food matrix composition (protein, polysaccharide, and fat content), ionic strength, and pH on the properties of thermally processed model emulsions (90°C/10min) 319:495 The influence of food matrix composition (protein, polysaccharide, and fat content), ionic strength, and pH on the properties of thermally processed model emulsions (90°C/10min) was investigated. 30011702 0 31 theme foods 31:35 arg1 microparticles 46:59 emulsion-based foods: Protein microparticles 16:59 emulsion-based foods: Protein microparticles 16:59 Reduced calorie emulsion-based foods: Protein microparticles and dietary fiber as fat replacers. 30011702 2 32 theme food 336:339 arg1 composition 348:358 food matrix composition 336:358 food matrix composition (protein, polysaccharide, and fat content) 336:401 The influence of food matrix composition (protein, polysaccharide, and fat content), ionic strength, and pH on the properties of thermally processed model emulsions (90°C/10min) was investigated. 30011702 4 33 theme creamy 686:691 arg1 appearance 699:708 a creamy white appearance 684:708 a creamy white appearance 684:708 All MWP-containing systems had a creamy white appearance with high lightness (L*>75). 30011702 2 34 theme fat 390:392 arg1 content 394:400 fat content 390:400 fat content 390:400 The influence of food matrix composition (protein, polysaccharide, and fat content), ionic strength, and pH on the properties of thermally processed model emulsions (90°C/10min) was investigated. 30011702 0 35 theme emulsion-based 16:29 arg1 microparticles 46:59 emulsion-based foods: Protein microparticles 16:59 emulsion-based foods: Protein microparticles 16:59 Reduced calorie emulsion-based foods: Protein microparticles and dietary fiber as fat replacers. 30011702 1 36 theme reduced 254:260 arg1 sauces 285:290 reduced calorie emulsion-based sauces 254:290 reduced calorie emulsion-based sauces 254:290 The potential of using microparticulated whey protein (MWP) in combination with either modified starch or locust bean gum (LBG) as fat mimetics to fabricate reduced calorie emulsion-based sauces and dressings was studied. 30011702 5 37 theme light 827:831 arg1 scattering 833:842 enhanced light scattering 818:842 enhanced light scattering 818:842 Addition of fat droplets (5%) further increased their lightness (L*>90) due to enhanced light scattering. 30011702 5 38 theme fat 751:753 arg1 droplets 755:762 fat droplets 751:762 fat droplets (5%) 751:767 Addition of fat droplets (5%) further increased their lightness (L*>90) due to enhanced light scattering. 30011702 5 38 theme fat 751:753 arg1 % 766:766 5% 765:766 5% 765:766 Addition of fat droplets (5%) further increased their lightness (L*>90) due to enhanced light scattering. 30011702 2 39 theme pH 424:425 arg1 influence 323:331 The influence 319:331 The influence of food matrix composition (protein, polysaccharide, and fat content), ionic strength, and pH on the properties of thermally processed model emulsions (90°C/10min) 319:495 The influence of food matrix composition (protein, polysaccharide, and fat content), ionic strength, and pH on the properties of thermally processed model emulsions (90°C/10min) was investigated. 30011702 1 40 theme calorie 262:268 arg1 sauces 285:290 reduced calorie emulsion-based sauces 254:290 reduced calorie emulsion-based sauces 254:290 The potential of using microparticulated whey protein (MWP) in combination with either modified starch or locust bean gum (LBG) as fat mimetics to fabricate reduced calorie emulsion-based sauces and dressings was studied. 30011702 3 41 theme particle 585:592 arg1 diameter 594:601 the mean (d3,2) particle diameter 569:601 the mean (d3,2) particle diameter 569:601 Increasing protein concentration (2.5-7.5%) increased the mean (d3,2) particle diameter due to the formation of large protein aggregates. 30011702 6 42 theme increased 917:925 arg1 fraction 944:951 the increased effective volume fraction 913:951 the increased effective volume fraction of the dispersed phase 913:974 Addition of starch, LBG, or MWP increased emulsion viscosity due to the increased effective volume fraction of the dispersed phase. 30011702 5 43 theme droplets 755:762 arg1 Addition 739:746 Addition 739:746 Addition of fat droplets (5%) 739:767 Addition of fat droplets (5%) further increased their lightness (L*>90) due to enhanced light scattering. 30011702 6 44 theme emulsion 887:894 arg1 viscosity 896:904 emulsion viscosity 887:904 emulsion viscosity 887:904 Addition of starch, LBG, or MWP increased emulsion viscosity due to the increased effective volume fraction of the dispersed phase. 30011702 1 45 theme emulsion-based 270:283 arg1 sauces 285:290 reduced calorie emulsion-based sauces 254:290 reduced calorie emulsion-based sauces 254:290 The potential of using microparticulated whey protein (MWP) in combination with either modified starch or locust bean gum (LBG) as fat mimetics to fabricate reduced calorie emulsion-based sauces and dressings was studied. 30011702 8 46 theme rheological 1142:1152 arg1 properties 1154:1163 rheological properties 1142:1163 rheological properties 1142:1163 Overall, the appearance and rheological properties of the mixed systems were similar to commercial sauces and dressings. 30011702 1 47 theme locust 203:208 arg1 LBG 220:222 LBG 220:222 LBG 220:222 The potential of using microparticulated whey protein (MWP) in combination with either modified starch or locust bean gum (LBG) as fat mimetics to fabricate reduced calorie emulsion-based sauces and dressings was studied. 30011702 1 47 theme locust 203:208 arg1 gum 215:217 locust bean gum 203:217 locust bean gum (LBG) 203:223 The potential of using microparticulated whey protein (MWP) in combination with either modified starch or locust bean gum (LBG) as fat mimetics to fabricate reduced calorie emulsion-based sauces and dressings was studied. 30011702 7 48 theme chloride 997:1004 arg1 Addition 977:984 Addition 977:984 Addition of calcium chloride (10mM) and pH adjustment (2-8) 977:1035 Addition of calcium chloride (10mM) and pH adjustment (2-8) caused little change in the physicochemical properties of the mixed systems. 30011702 3 49 theme d3,2 579:582 arg1 diameter 594:601 the mean (d3,2) particle diameter 569:601 the mean (d3,2) particle diameter 569:601 Increasing protein concentration (2.5-7.5%) increased the mean (d3,2) particle diameter due to the formation of large protein aggregates. 30011702 6 50 theme phase 970:974 arg1 fraction 944:951 the increased effective volume fraction 913:951 the increased effective volume fraction of the dispersed phase 913:974 Addition of starch, LBG, or MWP increased emulsion viscosity due to the increased effective volume fraction of the dispersed phase. 30011702 5 51 theme L 804:804 arg1 lightness 793:801 their lightness 787:801 their lightness (L*>90) 787:809 Addition of fat droplets (5%) further increased their lightness (L*>90) due to enhanced light scattering. 30011702 5 51 theme L 804:804 arg1 * 805:805 L*>90 804:808 L*>90 804:808 Addition of fat droplets (5%) further increased their lightness (L*>90) due to enhanced light scattering. 30011702 2 52 theme strength 410:417 arg1 influence 323:331 The influence 319:331 The influence of food matrix composition (protein, polysaccharide, and fat content), ionic strength, and pH on the properties of thermally processed model emulsions (90°C/10min) 319:495 The influence of food matrix composition (protein, polysaccharide, and fat content), ionic strength, and pH on the properties of thermally processed model emulsions (90°C/10min) was investigated. 30011702 9 53 theme full-fat 1347:1354 arg1 versions 1356:1363 full-fat versions 1347:1363 full-fat versions 1347:1363 This study demonstrates that reduced calorie food emulsions with appearance and consistency similar to those of full-fat versions can be formulated using protein microparticles and polysaccharides. 30011702 7 54 theme mixed 1099:1103 arg1 systems 1105:1111 the mixed systems 1095:1111 the mixed systems 1095:1111 Addition of calcium chloride (10mM) and pH adjustment (2-8) caused little change in the physicochemical properties of the mixed systems. 30011702 9 55 with emulsions 1285:1293 arg1 appearance 1300:1309 appearance 1300:1309 appearance 1300:1309 This study demonstrates that reduced calorie food emulsions with appearance and consistency similar to those of full-fat versions can be formulated using protein microparticles and polysaccharides. 30011702 9 55 with emulsions 1285:1293 arg1 consistency 1315:1325 consistency 1315:1325 consistency 1315:1325 This study demonstrates that reduced calorie food emulsions with appearance and consistency similar to those of full-fat versions can be formulated using protein microparticles and polysaccharides. 30011702 8 56 theme commercial 1202:1211 arg1 sauces 1213:1218 sauces 1213:1218 sauces 1213:1218 Overall, the appearance and rheological properties of the mixed systems were similar to commercial sauces and dressings. 30011702 1 57 theme microparticulated 120:136 arg1 MWP 152:154 MWP 152:154 MWP 152:154 The potential of using microparticulated whey protein (MWP) in combination with either modified starch or locust bean gum (LBG) as fat mimetics to fabricate reduced calorie emulsion-based sauces and dressings was studied. 30011702 1 57 theme microparticulated 120:136 arg1 protein 143:149 microparticulated whey protein 120:149 microparticulated whey protein (MWP) in combination with either modified starch or locust bean gum (LBG) 120:223 The potential of using microparticulated whey protein (MWP) in combination with either modified starch or locust bean gum (LBG) as fat mimetics to fabricate reduced calorie emulsion-based sauces and dressings was studied. 30011702 1 57 theme microparticulated 120:136 arg1 mimetics 232:239 fat mimetics 228:239 fat mimetics 228:239 The potential of using microparticulated whey protein (MWP) in combination with either modified starch or locust bean gum (LBG) as fat mimetics to fabricate reduced calorie emulsion-based sauces and dressings was studied. 30011702 5 58 theme enhanced 818:825 arg1 scattering 833:842 enhanced light scattering 818:842 enhanced light scattering 818:842 Addition of fat droplets (5%) further increased their lightness (L*>90) due to enhanced light scattering. 30011702 1 59 theme bean 210:213 arg1 LBG 220:222 LBG 220:222 LBG 220:222 The potential of using microparticulated whey protein (MWP) in combination with either modified starch or locust bean gum (LBG) as fat mimetics to fabricate reduced calorie emulsion-based sauces and dressings was studied. 30011702 1 59 theme bean 210:213 arg1 gum 215:217 locust bean gum 203:217 locust bean gum (LBG) 203:223 The potential of using microparticulated whey protein (MWP) in combination with either modified starch or locust bean gum (LBG) as fat mimetics to fabricate reduced calorie emulsion-based sauces and dressings was studied. 30011702 1 60 with combination 160:170 arg1 starch 193:198 modified starch 184:198 modified starch 184:198 The potential of using microparticulated whey protein (MWP) in combination with either modified starch or locust bean gum (LBG) as fat mimetics to fabricate reduced calorie emulsion-based sauces and dressings was studied. 30011702 1 60 with combination 160:170 arg1 LBG 220:222 LBG 220:222 LBG 220:222 The potential of using microparticulated whey protein (MWP) in combination with either modified starch or locust bean gum (LBG) as fat mimetics to fabricate reduced calorie emulsion-based sauces and dressings was studied. 30011702 1 60 with combination 160:170 arg1 gum 215:217 locust bean gum 203:217 locust bean gum (LBG) 203:223 The potential of using microparticulated whey protein (MWP) in combination with either modified starch or locust bean gum (LBG) as fat mimetics to fabricate reduced calorie emulsion-based sauces and dressings was studied. 30011702 9 61 theme reduced 1264:1270 arg1 emulsions 1285:1293 reduced calorie food emulsions 1264:1293 reduced calorie food emulsions with appearance and consistency similar to those of full-fat versions 1264:1363 This study demonstrates that reduced calorie food emulsions with appearance and consistency similar to those of full-fat versions can be formulated using protein microparticles and polysaccharides. 30011702 2 62 dep composition 348:358 arg1 protein 361:367 protein 361:367 protein 361:367 The influence of food matrix composition (protein, polysaccharide, and fat content), ionic strength, and pH on the properties of thermally processed model emulsions (90°C/10min) was investigated. 30011702 2 62 dep composition 348:358 arg1 content 394:400 fat content 390:400 fat content 390:400 The influence of food matrix composition (protein, polysaccharide, and fat content), ionic strength, and pH on the properties of thermally processed model emulsions (90°C/10min) was investigated. 30011702 2 62 dep composition 348:358 arg1 polysaccharide 370:383 polysaccharide 370:383 polysaccharide 370:383 The influence of food matrix composition (protein, polysaccharide, and fat content), ionic strength, and pH on the properties of thermally processed model emulsions (90°C/10min) was investigated. 30011702 1 63 theme whey 138:141 arg1 MWP 152:154 MWP 152:154 MWP 152:154 The potential of using microparticulated whey protein (MWP) in combination with either modified starch or locust bean gum (LBG) as fat mimetics to fabricate reduced calorie emulsion-based sauces and dressings was studied. 30011702 1 63 theme whey 138:141 arg1 protein 143:149 microparticulated whey protein 120:149 microparticulated whey protein (MWP) in combination with either modified starch or locust bean gum (LBG) 120:223 The potential of using microparticulated whey protein (MWP) in combination with either modified starch or locust bean gum (LBG) as fat mimetics to fabricate reduced calorie emulsion-based sauces and dressings was studied. 30011702 1 63 theme whey 138:141 arg1 mimetics 232:239 fat mimetics 228:239 fat mimetics 228:239 The potential of using microparticulated whey protein (MWP) in combination with either modified starch or locust bean gum (LBG) as fat mimetics to fabricate reduced calorie emulsion-based sauces and dressings was studied. 30011702 4 64 theme MWP-containing 657:670 arg1 systems 672:678 All MWP-containing systems 653:678 All MWP-containing systems 653:678 All MWP-containing systems had a creamy white appearance with high lightness (L*>75). 30011702 6 65 theme dispersed 960:968 arg1 phase 970:974 the dispersed phase 956:974 the dispersed phase 956:974 Addition of starch, LBG, or MWP increased emulsion viscosity due to the increased effective volume fraction of the dispersed phase. 30011702 8 66 dep appearance 1127:1136 arg1 the 1123:1125 the 1123:1125 the 1123:1125 Overall, the appearance and rheological properties of the mixed systems were similar to commercial sauces and dressings. 30011702 1 67 theme modified 184:191 arg1 starch 193:198 modified starch 184:198 modified starch 184:198 The potential of using microparticulated whey protein (MWP) in combination with either modified starch or locust bean gum (LBG) as fat mimetics to fabricate reduced calorie emulsion-based sauces and dressings was studied. 30011702 2 68 theme matrix 341:346 arg1 composition 348:358 food matrix composition 336:358 food matrix composition (protein, polysaccharide, and fat content) 336:401 The influence of food matrix composition (protein, polysaccharide, and fat content), ionic strength, and pH on the properties of thermally processed model emulsions (90°C/10min) was investigated. 30011702 7 69 theme physicochemical 1065:1079 arg1 properties 1081:1090 the physicochemical properties 1061:1090 the physicochemical properties of the mixed systems 1061:1111 Addition of calcium chloride (10mM) and pH adjustment (2-8) caused little change in the physicochemical properties of the mixed systems. 30011702 6 70 theme MWP 873:875 arg1 Addition 845:852 Addition 845:852 Addition of starch, LBG, or MWP 845:875 Addition of starch, LBG, or MWP increased emulsion viscosity due to the increased effective volume fraction of the dispersed phase. 30011702 0 71 theme dietary 65:71 arg1 fiber 73:77 dietary fiber 65:77 dietary fiber 65:77 Reduced calorie emulsion-based foods: Protein microparticles and dietary fiber as fat replacers. 30011702 3 72 theme large 627:631 arg1 aggregates 641:650 large protein aggregates 627:650 large protein aggregates 627:650 Increasing protein concentration (2.5-7.5%) increased the mean (d3,2) particle diameter due to the formation of large protein aggregates. 30011702 4 73 theme L 731:731 arg1 lightness 720:728 high lightness 715:728 high lightness (L*>75) 715:736 All MWP-containing systems had a creamy white appearance with high lightness (L*>75). 30011702 4 73 theme L 731:731 arg1 * 732:732 L*>75 731:735 L*>75 731:735 All MWP-containing systems had a creamy white appearance with high lightness (L*>75). 30011702 7 74 theme systems 1105:1111 arg1 properties 1081:1090 the physicochemical properties 1061:1090 the physicochemical properties of the mixed systems 1061:1111 Addition of calcium chloride (10mM) and pH adjustment (2-8) caused little change in the physicochemical properties of the mixed systems. 30011702 1 75 dep potential 101:109 arg1 fabricate 244:252 fabricate 244:252 to fabricate reduced calorie emulsion-based sauces and dressings 241:304 The potential of using microparticulated whey protein (MWP) in combination with either modified starch or locust bean gum (LBG) as fat mimetics to fabricate reduced calorie emulsion-based sauces and dressings was studied. 30011702 7 76 theme little 1044:1049 arg1 change 1051:1056 little change 1044:1056 little change 1044:1056 Addition of calcium chloride (10mM) and pH adjustment (2-8) caused little change in the physicochemical properties of the mixed systems. 24355330 0 0 theme hydrothermal 71:82 arg1 treatment 84:92 hydrothermal treatment 71:92 hydrothermal treatment 71:92 The role of temperature and CaCl2 in activated sludge dewatering under hydrothermal treatment. 24355330 7 1 theme compacted 1172:1180 arg1 structure 1187:1195 the compacted floc structure 1168:1195 the compacted floc structure 1168:1195 The integration of soluble biopolymers into the floc matrix by CaCl2 contributed to the compacted floc structure and thus improved the dewaterability. 24355330 3 2 theme solid 520:524 arg1 dry 516:518 as less as 20 mg/g dry solid (DS) 497:529 as less as 20 mg/g dry solid (DS) 497:529 Calcium chloride assisted hydrothermal treatment to improve the dewaterability of activated sludge, and eliminated the threshold temperature at as less as 20 mg/g dry solid (DS). 24355330 3 2 theme solid 520:524 arg1 DS 527:528 DS 527:528 DS 527:528 Calcium chloride assisted hydrothermal treatment to improve the dewaterability of activated sludge, and eliminated the threshold temperature at as less as 20 mg/g dry solid (DS). 24355330 8 3 from variation 1279:1287 arg1 structure 1317:1325 structure 1317:1325 structure 1317:1325 This work presents an insight into the floc variation in both the composition and structure associated with the dewaterability and offers a new understanding to the role of temperature and CaCl2 in hydrothermal treatment on activated sludge dewatering. 24355330 8 3 from variation 1279:1287 arg1 composition 1301:1311 composition 1301:1311 composition 1301:1311 This work presents an insight into the floc variation in both the composition and structure associated with the dewaterability and offers a new understanding to the role of temperature and CaCl2 in hydrothermal treatment on activated sludge dewatering. 24355330 4 4 theme till 579:582 arg1 DS 592:593 CaCl2 till 60 mg/g DS 573:593 CaCl2 till 60 mg/g DS 573:593 An increase in temperature and dosage of CaCl2 till 60 mg/g DS allowed a continuous improvement of dewaterability. 24355330 0 5 from role 4:7 arg1 sludge 47:52 activated sludge 37:52 activated sludge 37:52 The role of temperature and CaCl2 in activated sludge dewatering under hydrothermal treatment. 24355330 7 6 theme floc 1182:1185 arg1 structure 1187:1195 the compacted floc structure 1168:1195 the compacted floc structure 1168:1195 The integration of soluble biopolymers into the floc matrix by CaCl2 contributed to the compacted floc structure and thus improved the dewaterability. 24355330 4 7 theme CaCl2 573:577 arg1 DS 592:593 CaCl2 till 60 mg/g DS 573:593 CaCl2 till 60 mg/g DS 573:593 An increase in temperature and dosage of CaCl2 till 60 mg/g DS allowed a continuous improvement of dewaterability. 24355330 3 8 theme assisted 370:377 arg1 treatment 392:400 Calcium chloride assisted hydrothermal treatment 353:400 Calcium chloride assisted hydrothermal treatment 353:400 Calcium chloride assisted hydrothermal treatment to improve the dewaterability of activated sludge, and eliminated the threshold temperature at as less as 20 mg/g dry solid (DS). 24355330 4 9 theme DS 592:593 arg1 dosage 563:568 dosage 563:568 dosage 563:568 An increase in temperature and dosage of CaCl2 till 60 mg/g DS allowed a continuous improvement of dewaterability. 24355330 4 9 theme DS 592:593 arg1 temperature 547:557 temperature 547:557 temperature 547:557 An increase in temperature and dosage of CaCl2 till 60 mg/g DS allowed a continuous improvement of dewaterability. 24355330 3 10 theme hydrothermal 379:390 arg1 treatment 392:400 Calcium chloride assisted hydrothermal treatment 353:400 Calcium chloride assisted hydrothermal treatment 353:400 Calcium chloride assisted hydrothermal treatment to improve the dewaterability of activated sludge, and eliminated the threshold temperature at as less as 20 mg/g dry solid (DS). 24355330 6 11 theme protein 934:940 arg1 weight 916:921 molecular weight 906:921 molecular weight of soluble protein and polysaccharides 906:960 The variation of molecular weight of soluble protein and polysaccharides implies that CaCl2 interacted with the component of sludge and altered the constituent during the hydrothermal treatment. 24355330 4 12 theme 60 mg/g 584:590 arg1 DS 592:593 CaCl2 till 60 mg/g DS 573:593 CaCl2 till 60 mg/g DS 573:593 An increase in temperature and dosage of CaCl2 till 60 mg/g DS allowed a continuous improvement of dewaterability. 24355330 3 13 theme Calcium 353:359 arg1 treatment 392:400 Calcium chloride assisted hydrothermal treatment 353:400 Calcium chloride assisted hydrothermal treatment 353:400 Calcium chloride assisted hydrothermal treatment to improve the dewaterability of activated sludge, and eliminated the threshold temperature at as less as 20 mg/g dry solid (DS). 24355330 6 14 theme soluble 926:932 arg1 protein 934:940 soluble protein 926:940 soluble protein 926:940 The variation of molecular weight of soluble protein and polysaccharides implies that CaCl2 interacted with the component of sludge and altered the constituent during the hydrothermal treatment. 24355330 8 15 theme temperature 1408:1418 arg1 role 1400:1403 the role 1396:1403 the role of temperature and CaCl2 in hydrothermal treatment on activated sludge dewatering 1396:1485 This work presents an insight into the floc variation in both the composition and structure associated with the dewaterability and offers a new understanding to the role of temperature and CaCl2 in hydrothermal treatment on activated sludge dewatering. 24355330 5 16 theme water-binding 811:823 arg1 components 825:834 water-binding components 811:834 water-binding components 811:834 It is found that the charge neutralization resulted from biopolymers solubilization dominated the dewaterability evolution below 160 °C, while the decomposition of water-binding components played a more important role at higher temperatures. 24355330 3 17 theme chloride 361:368 arg1 treatment 392:400 Calcium chloride assisted hydrothermal treatment 353:400 Calcium chloride assisted hydrothermal treatment 353:400 Calcium chloride assisted hydrothermal treatment to improve the dewaterability of activated sludge, and eliminated the threshold temperature at as less as 20 mg/g dry solid (DS). 24355330 0 18 theme CaCl2 28:32 arg1 role 4:7 The role 0:7 The role of temperature and CaCl2 in activated sludge 0:52 The role of temperature and CaCl2 in activated sludge dewatering under hydrothermal treatment. 24355330 6 19 theme weight 916:921 arg1 variation 893:901 The variation 889:901 The variation of molecular weight of soluble protein and polysaccharides 889:960 The variation of molecular weight of soluble protein and polysaccharides implies that CaCl2 interacted with the component of sludge and altered the constituent during the hydrothermal treatment. 24355330 2 20 theme 130 °C 316:321 arg1 temperature 301:311 a threshold temperature 289:311 a threshold temperature of 130 °C under hydrothermal treatment 289:350 The dewaterability of activated sludge was first deteriorated and then ameliorated when the temperature was raised from 100 to 200 °C with a threshold temperature of 130 °C under hydrothermal treatment. 24355330 8 21 from treatment 1446:1454 arg1 dewatering 1476:1485 activated sludge dewatering 1459:1485 activated sludge dewatering 1459:1485 This work presents an insight into the floc variation in both the composition and structure associated with the dewaterability and offers a new understanding to the role of temperature and CaCl2 in hydrothermal treatment on activated sludge dewatering. 24355330 6 22 theme polysaccharides 946:960 arg1 weight 916:921 molecular weight 906:921 molecular weight of soluble protein and polysaccharides 906:960 The variation of molecular weight of soluble protein and polysaccharides implies that CaCl2 interacted with the component of sludge and altered the constituent during the hydrothermal treatment. 24355330 0 23 theme temperature 12:22 arg1 role 4:7 The role 0:7 The role of temperature and CaCl2 in activated sludge 0:52 The role of temperature and CaCl2 in activated sludge dewatering under hydrothermal treatment. 24355330 6 24 theme sludge 1014:1019 arg1 component 1001:1009 the component 997:1009 the component of sludge 997:1019 The variation of molecular weight of soluble protein and polysaccharides implies that CaCl2 interacted with the component of sludge and altered the constituent during the hydrothermal treatment. 24355330 5 25 theme biopolymers 704:714 arg1 solubilization 716:729 biopolymers solubilization 704:729 biopolymers solubilization 704:729 It is found that the charge neutralization resulted from biopolymers solubilization dominated the dewaterability evolution below 160 °C, while the decomposition of water-binding components played a more important role at higher temperatures. 24355330 8 26 theme hydrothermal 1433:1444 arg1 treatment 1446:1454 hydrothermal treatment 1433:1454 hydrothermal treatment on activated sludge dewatering 1433:1485 This work presents an insight into the floc variation in both the composition and structure associated with the dewaterability and offers a new understanding to the role of temperature and CaCl2 in hydrothermal treatment on activated sludge dewatering. 24355330 4 27 theme dewaterability 631:644 arg1 improvement 616:626 a continuous improvement 603:626 a continuous improvement of dewaterability 603:644 An increase in temperature and dosage of CaCl2 till 60 mg/g DS allowed a continuous improvement of dewaterability. 24355330 8 28 theme CaCl2 1424:1428 arg1 role 1400:1403 the role 1396:1403 the role of temperature and CaCl2 in hydrothermal treatment on activated sludge dewatering 1396:1485 This work presents an insight into the floc variation in both the composition and structure associated with the dewaterability and offers a new understanding to the role of temperature and CaCl2 in hydrothermal treatment on activated sludge dewatering. 24355330 7 29 theme floc 1132:1135 arg1 matrix 1137:1142 the floc matrix 1128:1142 the floc matrix 1128:1142 The integration of soluble biopolymers into the floc matrix by CaCl2 contributed to the compacted floc structure and thus improved the dewaterability. 24355330 6 30 theme molecular 906:914 arg1 weight 916:921 molecular weight 906:921 molecular weight of soluble protein and polysaccharides 906:960 The variation of molecular weight of soluble protein and polysaccharides implies that CaCl2 interacted with the component of sludge and altered the constituent during the hydrothermal treatment. 24355330 2 31 theme threshold 291:299 arg1 temperature 301:311 a threshold temperature 289:311 a threshold temperature of 130 °C under hydrothermal treatment 289:350 The dewaterability of activated sludge was first deteriorated and then ameliorated when the temperature was raised from 100 to 200 °C with a threshold temperature of 130 °C under hydrothermal treatment. 24355330 5 32 theme higher 868:873 arg1 temperatures 875:886 higher temperatures 868:886 higher temperatures 868:886 It is found that the charge neutralization resulted from biopolymers solubilization dominated the dewaterability evolution below 160 °C, while the decomposition of water-binding components played a more important role at higher temperatures. 24355330 3 33 theme activated 435:443 arg1 sludge 445:450 activated sludge 435:450 activated sludge 435:450 Calcium chloride assisted hydrothermal treatment to improve the dewaterability of activated sludge, and eliminated the threshold temperature at as less as 20 mg/g dry solid (DS). 24355330 7 34 theme biopolymers 1111:1121 arg1 integration 1088:1098 The integration 1084:1098 The integration of soluble biopolymers into the floc matrix by CaCl2 1084:1151 The integration of soluble biopolymers into the floc matrix by CaCl2 contributed to the compacted floc structure and thus improved the dewaterability. 24355330 2 35 theme sludge 182:187 arg1 dewaterability 154:167 The dewaterability 150:167 The dewaterability of activated sludge 150:187 The dewaterability of activated sludge was first deteriorated and then ameliorated when the temperature was raised from 100 to 200 °C with a threshold temperature of 130 °C under hydrothermal treatment. 24355330 8 36 from dewatering 1476:1485 arg1 role 1400:1403 the role 1396:1403 the role of temperature and CaCl2 in hydrothermal treatment on activated sludge dewatering 1396:1485 This work presents an insight into the floc variation in both the composition and structure associated with the dewaterability and offers a new understanding to the role of temperature and CaCl2 in hydrothermal treatment on activated sludge dewatering. 24355330 3 37 theme threshold 472:480 arg1 temperature 482:492 the threshold temperature 468:492 the threshold temperature 468:492 Calcium chloride assisted hydrothermal treatment to improve the dewaterability of activated sludge, and eliminated the threshold temperature at as less as 20 mg/g dry solid (DS). 24355330 3 38 theme sludge 445:450 arg1 dewaterability 417:430 the dewaterability 413:430 the dewaterability of activated sludge 413:450 Calcium chloride assisted hydrothermal treatment to improve the dewaterability of activated sludge, and eliminated the threshold temperature at as less as 20 mg/g dry solid (DS). 24355330 5 39 dep resulted 690:697 arg1 dominated 731:739 dominated 731:739 dominated 731:739 It is found that the charge neutralization resulted from biopolymers solubilization dominated the dewaterability evolution below 160 °C, while the decomposition of water-binding components played a more important role at higher temperatures. 24355330 4 40 from increase 535:542 arg1 dosage 563:568 dosage 563:568 dosage 563:568 An increase in temperature and dosage of CaCl2 till 60 mg/g DS allowed a continuous improvement of dewaterability. 24355330 4 40 from increase 535:542 arg1 temperature 547:557 temperature 547:557 temperature 547:557 An increase in temperature and dosage of CaCl2 till 60 mg/g DS allowed a continuous improvement of dewaterability. 24355330 2 41 theme activated 172:180 arg1 sludge 182:187 activated sludge 172:187 activated sludge 172:187 The dewaterability of activated sludge was first deteriorated and then ameliorated when the temperature was raised from 100 to 200 °C with a threshold temperature of 130 °C under hydrothermal treatment. 24355330 5 42 theme important 850:858 arg1 role 860:863 a more important role 843:863 a more important role 843:863 It is found that the charge neutralization resulted from biopolymers solubilization dominated the dewaterability evolution below 160 °C, while the decomposition of water-binding components played a more important role at higher temperatures. 24355330 0 43 theme activated 37:45 arg1 sludge 47:52 activated sludge 37:52 activated sludge 37:52 The role of temperature and CaCl2 in activated sludge dewatering under hydrothermal treatment. 24355330 5 44 theme dewaterability 745:758 arg1 evolution 760:768 the dewaterability evolution 741:768 the dewaterability evolution below 160 °C 741:781 It is found that the charge neutralization resulted from biopolymers solubilization dominated the dewaterability evolution below 160 °C, while the decomposition of water-binding components played a more important role at higher temperatures. 24355330 5 45 theme charge 668:673 arg1 neutralization 675:688 the charge neutralization 664:688 the charge neutralization 664:688 It is found that the charge neutralization resulted from biopolymers solubilization dominated the dewaterability evolution below 160 °C, while the decomposition of water-binding components played a more important role at higher temperatures. 24355330 8 46 dep composition 1301:1311 arg1 the 1297:1299 the 1297:1299 the 1297:1299 This work presents an insight into the floc variation in both the composition and structure associated with the dewaterability and offers a new understanding to the role of temperature and CaCl2 in hydrothermal treatment on activated sludge dewatering. 24355330 8 47 theme sludge 1469:1474 arg1 dewatering 1476:1485 activated sludge dewatering 1459:1485 activated sludge dewatering 1459:1485 This work presents an insight into the floc variation in both the composition and structure associated with the dewaterability and offers a new understanding to the role of temperature and CaCl2 in hydrothermal treatment on activated sludge dewatering. 24355330 8 48 theme floc 1274:1277 arg1 variation 1279:1287 the floc variation 1270:1287 the floc variation in both the composition and structure associated with the dewaterability 1270:1360 This work presents an insight into the floc variation in both the composition and structure associated with the dewaterability and offers a new understanding to the role of temperature and CaCl2 in hydrothermal treatment on activated sludge dewatering. 24355330 7 49 theme soluble 1103:1109 arg1 biopolymers 1111:1121 soluble biopolymers 1103:1121 soluble biopolymers 1103:1121 The integration of soluble biopolymers into the floc matrix by CaCl2 contributed to the compacted floc structure and thus improved the dewaterability. 24355330 8 50 theme activated 1459:1467 arg1 dewatering 1476:1485 activated sludge dewatering 1459:1485 activated sludge dewatering 1459:1485 This work presents an insight into the floc variation in both the composition and structure associated with the dewaterability and offers a new understanding to the role of temperature and CaCl2 in hydrothermal treatment on activated sludge dewatering. 24355330 2 51 theme hydrothermal 329:340 arg1 treatment 342:350 hydrothermal treatment 329:350 hydrothermal treatment 329:350 The dewaterability of activated sludge was first deteriorated and then ameliorated when the temperature was raised from 100 to 200 °C with a threshold temperature of 130 °C under hydrothermal treatment. 24355330 8 52 theme new 1375:1377 arg1 understanding 1379:1391 a new understanding 1373:1391 a new understanding to the role of temperature and CaCl2 in hydrothermal treatment on activated sludge dewatering 1373:1485 This work presents an insight into the floc variation in both the composition and structure associated with the dewaterability and offers a new understanding to the role of temperature and CaCl2 in hydrothermal treatment on activated sludge dewatering. 24355330 1 53 theme sludge 133:138 arg1 disposal 140:147 activated sludge disposal 123:147 activated sludge disposal 123:147 Dewatering is important for activated sludge disposal. 24355330 8 54 from role 1400:1403 arg1 treatment 1446:1454 hydrothermal treatment 1433:1454 hydrothermal treatment on activated sludge dewatering 1433:1485 This work presents an insight into the floc variation in both the composition and structure associated with the dewaterability and offers a new understanding to the role of temperature and CaCl2 in hydrothermal treatment on activated sludge dewatering. 24355330 8 54 from role 1400:1403 arg1 dewatering 1476:1485 activated sludge dewatering 1459:1485 activated sludge dewatering 1459:1485 This work presents an insight into the floc variation in both the composition and structure associated with the dewaterability and offers a new understanding to the role of temperature and CaCl2 in hydrothermal treatment on activated sludge dewatering. 24355330 1 55 theme activated 123:131 arg1 disposal 140:147 activated sludge disposal 123:147 activated sludge disposal 123:147 Dewatering is important for activated sludge disposal. 24355330 2 56 dep 200 °C 277:282 arg1 to 274:275 to 274:275 to 274:275 The dewaterability of activated sludge was first deteriorated and then ameliorated when the temperature was raised from 100 to 200 °C with a threshold temperature of 130 °C under hydrothermal treatment. 24355330 6 57 theme hydrothermal 1060:1071 arg1 treatment 1073:1081 the hydrothermal treatment 1056:1081 the hydrothermal treatment 1056:1081 The variation of molecular weight of soluble protein and polysaccharides implies that CaCl2 interacted with the component of sludge and altered the constituent during the hydrothermal treatment. 24355330 5 58 theme components 825:834 arg1 decomposition 794:806 the decomposition 790:806 the decomposition of water-binding components 790:834 It is found that the charge neutralization resulted from biopolymers solubilization dominated the dewaterability evolution below 160 °C, while the decomposition of water-binding components played a more important role at higher temperatures. 24355330 4 59 theme continuous 605:614 arg1 improvement 616:626 a continuous improvement 603:626 a continuous improvement of dewaterability 603:644 An increase in temperature and dosage of CaCl2 till 60 mg/g DS allowed a continuous improvement of dewaterability. 25805020 8 0 theme viral 1528:1532 arg1 lysis 1534:1538 viral lysis 1528:1538 viral lysis 1528:1538 The results have implications on management of nitrogen for both the synthesis of products from algae and product recovery via viral lysis. 25805020 7 1 theme nitrogen 1309:1316 arg1 content 1318:1324 the nitrogen content 1305:1324 the nitrogen content in C. variabilis 1305:1341 After virus infection, cells with a low C/N ratio produced a 7.6 times higher burst size than cells with a high C/N ratio, suggesting that the nitrogen content in C. variabilis has a large influence on viral production and cell lysis. 25805020 7 2 theme high 1273:1276 arg1 ratio 1282:1286 a high C/N ratio 1271:1286 a high C/N ratio 1271:1286 After virus infection, cells with a low C/N ratio produced a 7.6 times higher burst size than cells with a high C/N ratio, suggesting that the nitrogen content in C. variabilis has a large influence on viral production and cell lysis. 25805020 4 3 theme starch 676:681 arg1 accumulation 683:694 Cytoplasmic starch accumulation 664:694 Cytoplasmic starch accumulation 664:694 Cytoplasmic starch accumulation increased from 5% to approximately 35% of the total dry weight when yeast extract decreased from 1 to 0.25 g L(-1). 25805020 8 4 from implications 1418:1429 arg1 management 1434:1443 management 1434:1443 management of nitrogen 1434:1455 The results have implications on management of nitrogen for both the synthesis of products from algae and product recovery via viral lysis. 25805020 3 5 theme NC64A 538:542 arg1 physiology 544:553 Chlorella variabilis NC64A physiology 517:553 Chlorella variabilis NC64A physiology 517:553 The concentration of yeast extract and presence of KNO3 in algae cultivation media were investigated to observe their effects on Chlorella variabilis NC64A physiology and composition and the subsequent effect on production of Chlorella virus and disruption of infected cells. 25805020 7 6 contain has 1343:1345 arg2 influence 1355:1363 a large influence 1347:1363 a large influence on viral production and cell lysis 1347:1398 After virus infection, cells with a low C/N ratio produced a 7.6 times higher burst size than cells with a high C/N ratio, suggesting that the nitrogen content in C. variabilis has a large influence on viral production and cell lysis. 25805020 7 6 contain has 1343:1345 arg1 content 1318:1324 the nitrogen content 1305:1324 the nitrogen content in C. variabilis 1305:1341 After virus infection, cells with a low C/N ratio produced a 7.6 times higher burst size than cells with a high C/N ratio, suggesting that the nitrogen content in C. variabilis has a large influence on viral production and cell lysis. 25805020 3 7 theme subsequent 579:588 arg1 effect 590:595 the subsequent effect 575:595 the subsequent effect on production of Chlorella virus and disruption of infected cells 575:661 The concentration of yeast extract and presence of KNO3 in algae cultivation media were investigated to observe their effects on Chlorella variabilis NC64A physiology and composition and the subsequent effect on production of Chlorella virus and disruption of infected cells. 25805020 7 8 dep size 1250:1253 arg1 times 1231:1235 times 1231:1235 times 1231:1235 After virus infection, cells with a low C/N ratio produced a 7.6 times higher burst size than cells with a high C/N ratio, suggesting that the nitrogen content in C. variabilis has a large influence on viral production and cell lysis. 25805020 6 9 theme biomass 1064:1070 arg1 ratio 1045:1049 The C/N ratio 1037:1049 The C/N ratio of the algal biomass 1037:1070 The C/N ratio of the algal biomass decreased by a factor of approximately 2 when yeast extract increased from 0.25 to 1 g L(-1). 25805020 7 10 from content 1318:1324 arg1 variabilis 1332:1341 C. variabilis 1329:1341 C. variabilis 1329:1341 After virus infection, cells with a low C/N ratio produced a 7.6 times higher burst size than cells with a high C/N ratio, suggesting that the nitrogen content in C. variabilis has a large influence on viral production and cell lysis. 25805020 7 11 theme burst 1244:1248 arg1 size 1250:1253 a 7.6 times higher burst size 1225:1253 a 7.6 times higher burst size 1225:1253 After virus infection, cells with a low C/N ratio produced a 7.6 times higher burst size than cells with a high C/N ratio, suggesting that the nitrogen content in C. variabilis has a large influence on viral production and cell lysis. 25805020 7 12 with cells 1189:1193 arg1 ratio 1210:1214 a low C/N ratio 1200:1214 a low C/N ratio 1200:1214 After virus infection, cells with a low C/N ratio produced a 7.6 times higher burst size than cells with a high C/N ratio, suggesting that the nitrogen content in C. variabilis has a large influence on viral production and cell lysis. 25805020 8 13 from synthesis 1470:1478 arg1 algae 1497:1501 algae 1497:1501 algae 1497:1501 The results have implications on management of nitrogen for both the synthesis of products from algae and product recovery via viral lysis. 25805020 5 14 theme total 874:878 arg1 polysaccharide 880:893 the total polysaccharide 870:893 the total polysaccharide 870:893 When cells were cultured with the lowest nitrogen levels, the total polysaccharide accounted for more than 50% of the cell wall, which was 1.7 times higher than the content in cells cultured with the highest nitrogen levels. 25805020 8 15 contain have 1413:1416 arg2 implications 1418:1429 implications 1418:1429 implications on management of nitrogen for both the synthesis of products from algae and product recovery 1418:1522 The results have implications on management of nitrogen for both the synthesis of products from algae and product recovery via viral lysis. 25805020 8 15 contain have 1413:1416 arg1 results 1405:1411 The results 1401:1411 The results 1401:1411 The results have implications on management of nitrogen for both the synthesis of products from algae and product recovery via viral lysis. 25805020 8 16 from recovery 1515:1522 arg1 algae 1497:1501 algae 1497:1501 algae 1497:1501 The results have implications on management of nitrogen for both the synthesis of products from algae and product recovery via viral lysis. 25805020 3 17 theme disruption 634:643 arg1 production 600:609 production 600:609 production of Chlorella virus and disruption of infected cells 600:661 The concentration of yeast extract and presence of KNO3 in algae cultivation media were investigated to observe their effects on Chlorella variabilis NC64A physiology and composition and the subsequent effect on production of Chlorella virus and disruption of infected cells. 25805020 3 18 from concentration 392:404 arg1 media 465:469 algae cultivation media 447:469 algae cultivation media 447:469 The concentration of yeast extract and presence of KNO3 in algae cultivation media were investigated to observe their effects on Chlorella variabilis NC64A physiology and composition and the subsequent effect on production of Chlorella virus and disruption of infected cells. 25805020 3 19 theme virus 624:628 arg1 production 600:609 production 600:609 production of Chlorella virus and disruption of infected cells 600:661 The concentration of yeast extract and presence of KNO3 in algae cultivation media were investigated to observe their effects on Chlorella variabilis NC64A physiology and composition and the subsequent effect on production of Chlorella virus and disruption of infected cells. 25805020 5 20 theme nitrogen 853:860 arg1 levels 862:867 the lowest nitrogen levels 842:867 the lowest nitrogen levels 842:867 When cells were cultured with the lowest nitrogen levels, the total polysaccharide accounted for more than 50% of the cell wall, which was 1.7 times higher than the content in cells cultured with the highest nitrogen levels. 25805020 5 21 from content 977:983 arg1 cells 988:992 cells 988:992 cells cultured with the highest nitrogen levels 988:1034 When cells were cultured with the lowest nitrogen levels, the total polysaccharide accounted for more than 50% of the cell wall, which was 1.7 times higher than the content in cells cultured with the highest nitrogen levels. 25805020 7 22 theme 7.6 1227:1229 arg1 times 1231:1235 times 1231:1235 times 1231:1235 After virus infection, cells with a low C/N ratio produced a 7.6 times higher burst size than cells with a high C/N ratio, suggesting that the nitrogen content in C. variabilis has a large influence on viral production and cell lysis. 25805020 4 23 theme yeast 764:768 arg1 extract 770:776 yeast extract 764:776 yeast extract 764:776 Cytoplasmic starch accumulation increased from 5% to approximately 35% of the total dry weight when yeast extract decreased from 1 to 0.25 g L(-1). 25805020 0 24 theme Viral 93:97 arg1 Production 99:108 Viral Production 93:108 Viral Production 93:108 Organic and Inorganic Nitrogen Impact Chlorella variabilis Productivity and Host Quality for Viral Production and Cell Lysis. 25805020 5 25 theme nitrogen 1020:1027 arg1 levels 1029:1034 the highest nitrogen levels 1008:1034 the highest nitrogen levels 1008:1034 When cells were cultured with the lowest nitrogen levels, the total polysaccharide accounted for more than 50% of the cell wall, which was 1.7 times higher than the content in cells cultured with the highest nitrogen levels. 25805020 5 26 theme cell 930:933 arg1 times 955:959 times 955:959 times 955:959 When cells were cultured with the lowest nitrogen levels, the total polysaccharide accounted for more than 50% of the cell wall, which was 1.7 times higher than the content in cells cultured with the highest nitrogen levels. 25805020 5 26 theme cell 930:933 arg1 wall 935:938 the cell wall 926:938 the cell wall 926:938 When cells were cultured with the lowest nitrogen levels, the total polysaccharide accounted for more than 50% of the cell wall, which was 1.7 times higher than the content in cells cultured with the highest nitrogen levels. 25805020 7 27 theme C/N 1206:1208 arg1 ratio 1210:1214 a low C/N ratio 1200:1214 a low C/N ratio 1200:1214 After virus infection, cells with a low C/N ratio produced a 7.6 times higher burst size than cells with a high C/N ratio, suggesting that the nitrogen content in C. variabilis has a large influence on viral production and cell lysis. 25805020 4 28 theme total 742:746 arg1 weight 752:757 the total dry weight 738:757 the total dry weight 738:757 Cytoplasmic starch accumulation increased from 5% to approximately 35% of the total dry weight when yeast extract decreased from 1 to 0.25 g L(-1). 25805020 0 29 theme Organic 0:6 arg1 Quality 81:87 Host Quality 76:87 Host Quality 76:87 Organic and Inorganic Nitrogen Impact Chlorella variabilis Productivity and Host Quality for Viral Production and Cell Lysis. 25805020 0 29 theme Organic 0:6 arg1 variabilis 48:57 Organic and Inorganic Nitrogen Impact Chlorella variabilis Productivity and Host Quality 0:87 Organic and Inorganic Nitrogen Impact Chlorella variabilis Productivity and Host Quality for Viral Production and Cell Lysis. 0:124 Organic and Inorganic Nitrogen Impact Chlorella variabilis Productivity and Host Quality for Viral Production and Cell Lysis. 25805020 0 29 theme Organic 0:6 arg1 Productivity 59:70 Productivity 59:70 Productivity 59:70 Organic and Inorganic Nitrogen Impact Chlorella variabilis Productivity and Host Quality for Viral Production and Cell Lysis. 25805020 4 30 theme weight 752:757 arg1 weight 752:757 the total dry weight 738:757 the total dry weight 738:757 Cytoplasmic starch accumulation increased from 5% to approximately 35% of the total dry weight when yeast extract decreased from 1 to 0.25 g L(-1). 25805020 4 30 theme weight 752:757 arg1 % 733:733 approximately 35% 717:733 approximately 35% of the total dry weight 717:757 Cytoplasmic starch accumulation increased from 5% to approximately 35% of the total dry weight when yeast extract decreased from 1 to 0.25 g L(-1). 25805020 3 31 theme cultivation 453:463 arg1 media 465:469 algae cultivation media 447:469 algae cultivation media 447:469 The concentration of yeast extract and presence of KNO3 in algae cultivation media were investigated to observe their effects on Chlorella variabilis NC64A physiology and composition and the subsequent effect on production of Chlorella virus and disruption of infected cells. 25805020 0 32 theme Inorganic 12:20 arg1 Quality 81:87 Host Quality 76:87 Host Quality 76:87 Organic and Inorganic Nitrogen Impact Chlorella variabilis Productivity and Host Quality for Viral Production and Cell Lysis. 25805020 0 32 theme Inorganic 12:20 arg1 variabilis 48:57 Organic and Inorganic Nitrogen Impact Chlorella variabilis Productivity and Host Quality 0:87 Organic and Inorganic Nitrogen Impact Chlorella variabilis Productivity and Host Quality for Viral Production and Cell Lysis. 0:124 Organic and Inorganic Nitrogen Impact Chlorella variabilis Productivity and Host Quality for Viral Production and Cell Lysis. 25805020 0 32 theme Inorganic 12:20 arg1 Productivity 59:70 Productivity 59:70 Productivity 59:70 Organic and Inorganic Nitrogen Impact Chlorella variabilis Productivity and Host Quality for Viral Production and Cell Lysis. 25805020 1 33 theme cytoplasmic 284:294 arg1 polysaccharides 296:310 cytoplasmic polysaccharides 284:310 cytoplasmic polysaccharides 284:310 Microalgae have been proposed as a potential feedstock for biofuel production; however, cell disruption is usually required for collection and utilization of cytoplasmic polysaccharides and lipids. 25805020 3 34 theme yeast 409:413 arg1 extract 415:421 yeast extract 409:421 yeast extract 409:421 The concentration of yeast extract and presence of KNO3 in algae cultivation media were investigated to observe their effects on Chlorella variabilis NC64A physiology and composition and the subsequent effect on production of Chlorella virus and disruption of infected cells. 25805020 7 35 dep times 1231:1235 arg1 higher 1237:1242 higher 1237:1242 higher 1237:1242 After virus infection, cells with a low C/N ratio produced a 7.6 times higher burst size than cells with a high C/N ratio, suggesting that the nitrogen content in C. variabilis has a large influence on viral production and cell lysis. 25805020 0 36 theme Impact 31:36 arg1 Quality 81:87 Host Quality 76:87 Host Quality 76:87 Organic and Inorganic Nitrogen Impact Chlorella variabilis Productivity and Host Quality for Viral Production and Cell Lysis. 25805020 0 36 theme Impact 31:36 arg1 variabilis 48:57 Organic and Inorganic Nitrogen Impact Chlorella variabilis Productivity and Host Quality 0:87 Organic and Inorganic Nitrogen Impact Chlorella variabilis Productivity and Host Quality for Viral Production and Cell Lysis. 0:124 Organic and Inorganic Nitrogen Impact Chlorella variabilis Productivity and Host Quality for Viral Production and Cell Lysis. 25805020 0 36 theme Impact 31:36 arg1 Productivity 59:70 Productivity 59:70 Productivity 59:70 Organic and Inorganic Nitrogen Impact Chlorella variabilis Productivity and Host Quality for Viral Production and Cell Lysis. 25805020 0 37 dep variabilis 48:57 arg1 Quality 81:87 Host Quality 76:87 Host Quality 76:87 Organic and Inorganic Nitrogen Impact Chlorella variabilis Productivity and Host Quality for Viral Production and Cell Lysis. 25805020 0 37 dep variabilis 48:57 arg1 variabilis 48:57 Organic and Inorganic Nitrogen Impact Chlorella variabilis Productivity and Host Quality 0:87 Organic and Inorganic Nitrogen Impact Chlorella variabilis Productivity and Host Quality for Viral Production and Cell Lysis. 0:124 Organic and Inorganic Nitrogen Impact Chlorella variabilis Productivity and Host Quality for Viral Production and Cell Lysis. 25805020 0 37 dep variabilis 48:57 arg1 Productivity 59:70 Productivity 59:70 Productivity 59:70 Organic and Inorganic Nitrogen Impact Chlorella variabilis Productivity and Host Quality for Viral Production and Cell Lysis. 25805020 3 38 theme infected 648:655 arg1 cells 657:661 infected cells 648:661 infected cells 648:661 The concentration of yeast extract and presence of KNO3 in algae cultivation media were investigated to observe their effects on Chlorella variabilis NC64A physiology and composition and the subsequent effect on production of Chlorella virus and disruption of infected cells. 25805020 7 39 with cells 1260:1264 arg1 ratio 1282:1286 a high C/N ratio 1271:1286 a high C/N ratio 1271:1286 After virus infection, cells with a low C/N ratio produced a 7.6 times higher burst size than cells with a high C/N ratio, suggesting that the nitrogen content in C. variabilis has a large influence on viral production and cell lysis. 25805020 7 40 theme large 1349:1353 arg1 influence 1355:1363 a large influence 1347:1363 a large influence on viral production and cell lysis 1347:1398 After virus infection, cells with a low C/N ratio produced a 7.6 times higher burst size than cells with a high C/N ratio, suggesting that the nitrogen content in C. variabilis has a large influence on viral production and cell lysis. 25805020 8 41 theme products 1483:1490 arg1 recovery 1515:1522 product recovery 1507:1522 product recovery 1507:1522 The results have implications on management of nitrogen for both the synthesis of products from algae and product recovery via viral lysis. 25805020 8 41 theme products 1483:1490 arg1 synthesis 1470:1478 the synthesis 1466:1478 the synthesis of products from algae 1466:1501 The results have implications on management of nitrogen for both the synthesis of products from algae and product recovery via viral lysis. 25805020 1 42 theme cell 214:217 arg1 disruption 219:228 cell disruption 214:228 cell disruption 214:228 Microalgae have been proposed as a potential feedstock for biofuel production; however, cell disruption is usually required for collection and utilization of cytoplasmic polysaccharides and lipids. 25805020 6 43 theme C/N 1041:1043 arg1 ratio 1045:1049 The C/N ratio 1037:1049 The C/N ratio of the algal biomass 1037:1070 The C/N ratio of the algal biomass decreased by a factor of approximately 2 when yeast extract increased from 0.25 to 1 g L(-1). 25805020 3 44 from presence 427:434 arg1 media 465:469 algae cultivation media 447:469 algae cultivation media 447:469 The concentration of yeast extract and presence of KNO3 in algae cultivation media were investigated to observe their effects on Chlorella variabilis NC64A physiology and composition and the subsequent effect on production of Chlorella virus and disruption of infected cells. 25805020 6 45 dep 1 1155:1155 arg1 to 1152:1153 to 1152:1153 to 1152:1153 The C/N ratio of the algal biomass decreased by a factor of approximately 2 when yeast extract increased from 0.25 to 1 g L(-1). 25805020 7 46 theme C. 1329:1330 arg1 variabilis 1332:1341 C. variabilis 1329:1341 C. variabilis 1329:1341 After virus infection, cells with a low C/N ratio produced a 7.6 times higher burst size than cells with a high C/N ratio, suggesting that the nitrogen content in C. variabilis has a large influence on viral production and cell lysis. 25805020 8 47 theme nitrogen 1448:1455 arg1 management 1434:1443 management 1434:1443 management of nitrogen 1434:1455 The results have implications on management of nitrogen for both the synthesis of products from algae and product recovery via viral lysis. 25805020 8 48 theme product 1507:1513 arg1 recovery 1515:1522 product recovery 1507:1522 product recovery 1507:1522 The results have implications on management of nitrogen for both the synthesis of products from algae and product recovery via viral lysis. 25805020 7 49 from influence 1355:1363 arg1 production 1374:1383 viral production 1368:1383 viral production 1368:1383 After virus infection, cells with a low C/N ratio produced a 7.6 times higher burst size than cells with a high C/N ratio, suggesting that the nitrogen content in C. variabilis has a large influence on viral production and cell lysis. 25805020 7 49 from influence 1355:1363 arg1 lysis 1394:1398 cell lysis 1389:1398 cell lysis 1389:1398 After virus infection, cells with a low C/N ratio produced a 7.6 times higher burst size than cells with a high C/N ratio, suggesting that the nitrogen content in C. variabilis has a large influence on viral production and cell lysis. 25805020 3 50 from effects 506:512 arg1 production 600:609 production 600:609 production of Chlorella virus and disruption of infected cells 600:661 The concentration of yeast extract and presence of KNO3 in algae cultivation media were investigated to observe their effects on Chlorella variabilis NC64A physiology and composition and the subsequent effect on production of Chlorella virus and disruption of infected cells. 25805020 3 50 from effects 506:512 arg1 physiology 544:553 Chlorella variabilis NC64A physiology 517:553 Chlorella variabilis NC64A physiology 517:553 The concentration of yeast extract and presence of KNO3 in algae cultivation media were investigated to observe their effects on Chlorella variabilis NC64A physiology and composition and the subsequent effect on production of Chlorella virus and disruption of infected cells. 25805020 3 50 from effects 506:512 arg1 composition 559:569 composition 559:569 composition 559:569 The concentration of yeast extract and presence of KNO3 in algae cultivation media were investigated to observe their effects on Chlorella variabilis NC64A physiology and composition and the subsequent effect on production of Chlorella virus and disruption of infected cells. 25805020 3 51 theme variabilis 527:536 arg1 physiology 544:553 Chlorella variabilis NC64A physiology 517:553 Chlorella variabilis NC64A physiology 517:553 The concentration of yeast extract and presence of KNO3 in algae cultivation media were investigated to observe their effects on Chlorella variabilis NC64A physiology and composition and the subsequent effect on production of Chlorella virus and disruption of infected cells. 25805020 1 52 theme potential 161:169 arg1 Microalgae 126:135 Microalgae 126:135 Microalgae 126:135 Microalgae have been proposed as a potential feedstock for biofuel production; however, cell disruption is usually required for collection and utilization of cytoplasmic polysaccharides and lipids. 25805020 1 52 theme potential 161:169 arg1 feedstock 171:179 a potential feedstock 159:179 a potential feedstock for biofuel production 159:202 Microalgae have been proposed as a potential feedstock for biofuel production; however, cell disruption is usually required for collection and utilization of cytoplasmic polysaccharides and lipids. 25805020 7 53 theme C/N 1278:1280 arg1 ratio 1282:1286 a high C/N ratio 1271:1286 a high C/N ratio 1271:1286 After virus infection, cells with a low C/N ratio produced a 7.6 times higher burst size than cells with a high C/N ratio, suggesting that the nitrogen content in C. variabilis has a large influence on viral production and cell lysis. 25805020 4 54 theme Cytoplasmic 664:674 arg1 accumulation 683:694 Cytoplasmic starch accumulation 664:694 Cytoplasmic starch accumulation 664:694 Cytoplasmic starch accumulation increased from 5% to approximately 35% of the total dry weight when yeast extract decreased from 1 to 0.25 g L(-1). 25805020 6 55 theme g 1157:1157 arg1 L 1159:1159 0.25 to 1 g L(-1) 1147:1163 0.25 to 1 g L(-1) 1147:1163 The C/N ratio of the algal biomass decreased by a factor of approximately 2 when yeast extract increased from 0.25 to 1 g L(-1). 25805020 2 56 theme Virus 324:328 arg1 infection 330:338 Virus infection 324:338 Virus infection 324:338 Virus infection might be one approach to disrupt the cell wall. 25805020 3 57 attach presence 427:434 arg2 extract 415:421 yeast extract 409:421 yeast extract 409:421 The concentration of yeast extract and presence of KNO3 in algae cultivation media were investigated to observe their effects on Chlorella variabilis NC64A physiology and composition and the subsequent effect on production of Chlorella virus and disruption of infected cells. 25805020 3 57 attach presence 427:434 arg2 KNO3 439:442 KNO3 439:442 KNO3 439:442 The concentration of yeast extract and presence of KNO3 in algae cultivation media were investigated to observe their effects on Chlorella variabilis NC64A physiology and composition and the subsequent effect on production of Chlorella virus and disruption of infected cells. 25805020 3 57 attach presence 427:434 arg1 media 465:469 algae cultivation media 447:469 algae cultivation media 447:469 The concentration of yeast extract and presence of KNO3 in algae cultivation media were investigated to observe their effects on Chlorella variabilis NC64A physiology and composition and the subsequent effect on production of Chlorella virus and disruption of infected cells. 25805020 5 58 dep times 955:959 arg1 higher 961:966 higher 961:966 higher 961:966 When cells were cultured with the lowest nitrogen levels, the total polysaccharide accounted for more than 50% of the cell wall, which was 1.7 times higher than the content in cells cultured with the highest nitrogen levels. 25805020 6 59 theme algal 1058:1062 arg1 biomass 1064:1070 the algal biomass 1054:1070 the algal biomass 1054:1070 The C/N ratio of the algal biomass decreased by a factor of approximately 2 when yeast extract increased from 0.25 to 1 g L(-1). 25805020 1 60 theme biofuel 185:191 arg1 production 193:202 biofuel production 185:202 biofuel production 185:202 Microalgae have been proposed as a potential feedstock for biofuel production; however, cell disruption is usually required for collection and utilization of cytoplasmic polysaccharides and lipids. 25805020 4 61 dep L 805:805 arg1 to 795:796 to 795:796 to 795:796 Cytoplasmic starch accumulation increased from 5% to approximately 35% of the total dry weight when yeast extract decreased from 1 to 0.25 g L(-1). 25805020 5 62 theme highest 1012:1018 arg1 levels 1029:1034 the highest nitrogen levels 1008:1034 the highest nitrogen levels 1008:1034 When cells were cultured with the lowest nitrogen levels, the total polysaccharide accounted for more than 50% of the cell wall, which was 1.7 times higher than the content in cells cultured with the highest nitrogen levels. 25805020 6 63 theme yeast 1118:1122 arg1 extract 1124:1130 yeast extract 1118:1130 yeast extract 1118:1130 The C/N ratio of the algal biomass decreased by a factor of approximately 2 when yeast extract increased from 0.25 to 1 g L(-1). 25805020 0 64 theme Host 76:79 arg1 Quality 81:87 Host Quality 76:87 Host Quality 76:87 Organic and Inorganic Nitrogen Impact Chlorella variabilis Productivity and Host Quality for Viral Production and Cell Lysis. 25805020 0 64 theme Host 76:79 arg1 variabilis 48:57 Organic and Inorganic Nitrogen Impact Chlorella variabilis Productivity and Host Quality 0:87 Organic and Inorganic Nitrogen Impact Chlorella variabilis Productivity and Host Quality for Viral Production and Cell Lysis. 0:124 Organic and Inorganic Nitrogen Impact Chlorella variabilis Productivity and Host Quality for Viral Production and Cell Lysis. 25805020 3 65 theme Chlorella 614:622 arg1 virus 624:628 Chlorella virus 614:628 Chlorella virus 614:628 The concentration of yeast extract and presence of KNO3 in algae cultivation media were investigated to observe their effects on Chlorella variabilis NC64A physiology and composition and the subsequent effect on production of Chlorella virus and disruption of infected cells. 25805020 5 66 theme lowest 846:851 arg1 levels 862:867 the lowest nitrogen levels 842:867 the lowest nitrogen levels 842:867 When cells were cultured with the lowest nitrogen levels, the total polysaccharide accounted for more than 50% of the cell wall, which was 1.7 times higher than the content in cells cultured with the highest nitrogen levels. 25805020 6 67 theme 2 1111:1111 arg1 factor 1087:1092 a factor 1085:1092 a factor of approximately 2 1085:1111 The C/N ratio of the algal biomass decreased by a factor of approximately 2 when yeast extract increased from 0.25 to 1 g L(-1). 25805020 7 68 theme cell 1389:1392 arg1 lysis 1394:1398 cell lysis 1389:1398 cell lysis 1389:1398 After virus infection, cells with a low C/N ratio produced a 7.6 times higher burst size than cells with a high C/N ratio, suggesting that the nitrogen content in C. variabilis has a large influence on viral production and cell lysis. 25805020 8 69 from algae 1497:1501 arg1 recovery 1515:1522 product recovery 1507:1522 product recovery 1507:1522 The results have implications on management of nitrogen for both the synthesis of products from algae and product recovery via viral lysis. 25805020 8 69 from algae 1497:1501 arg1 products 1483:1490 products 1483:1490 products from algae 1483:1501 The results have implications on management of nitrogen for both the synthesis of products from algae and product recovery via viral lysis. 25805020 8 69 from algae 1497:1501 arg1 synthesis 1470:1478 the synthesis 1466:1478 the synthesis of products from algae 1466:1501 The results have implications on management of nitrogen for both the synthesis of products from algae and product recovery via viral lysis. 25805020 0 70 theme Cell 114:117 arg1 Lysis 119:123 Cell Lysis 114:123 Cell Lysis 114:123 Organic and Inorganic Nitrogen Impact Chlorella variabilis Productivity and Host Quality for Viral Production and Cell Lysis. 25805020 7 71 theme low 1202:1204 arg1 ratio 1210:1214 a low C/N ratio 1200:1214 a low C/N ratio 1200:1214 After virus infection, cells with a low C/N ratio produced a 7.6 times higher burst size than cells with a high C/N ratio, suggesting that the nitrogen content in C. variabilis has a large influence on viral production and cell lysis. 25805020 3 72 theme KNO3 439:442 arg1 presence 427:434 presence 427:434 presence 427:434 The concentration of yeast extract and presence of KNO3 in algae cultivation media were investigated to observe their effects on Chlorella variabilis NC64A physiology and composition and the subsequent effect on production of Chlorella virus and disruption of infected cells. 25805020 3 72 theme KNO3 439:442 arg1 concentration 392:404 The concentration 388:404 The concentration of yeast extract 388:421 The concentration of yeast extract and presence of KNO3 in algae cultivation media were investigated to observe their effects on Chlorella variabilis NC64A physiology and composition and the subsequent effect on production of Chlorella virus and disruption of infected cells. 25805020 3 73 from effect 590:595 arg1 production 600:609 production 600:609 production of Chlorella virus and disruption of infected cells 600:661 The concentration of yeast extract and presence of KNO3 in algae cultivation media were investigated to observe their effects on Chlorella variabilis NC64A physiology and composition and the subsequent effect on production of Chlorella virus and disruption of infected cells. 25805020 3 73 from effect 590:595 arg1 physiology 544:553 Chlorella variabilis NC64A physiology 517:553 Chlorella variabilis NC64A physiology 517:553 The concentration of yeast extract and presence of KNO3 in algae cultivation media were investigated to observe their effects on Chlorella variabilis NC64A physiology and composition and the subsequent effect on production of Chlorella virus and disruption of infected cells. 25805020 3 73 from effect 590:595 arg1 composition 559:569 composition 559:569 composition 559:569 The concentration of yeast extract and presence of KNO3 in algae cultivation media were investigated to observe their effects on Chlorella variabilis NC64A physiology and composition and the subsequent effect on production of Chlorella virus and disruption of infected cells. 25805020 2 74 theme cell 377:380 arg1 wall 382:385 the cell wall 373:385 the cell wall 373:385 Virus infection might be one approach to disrupt the cell wall. 25805020 0 75 theme Nitrogen 22:29 arg1 Quality 81:87 Host Quality 76:87 Host Quality 76:87 Organic and Inorganic Nitrogen Impact Chlorella variabilis Productivity and Host Quality for Viral Production and Cell Lysis. 25805020 0 75 theme Nitrogen 22:29 arg1 variabilis 48:57 Organic and Inorganic Nitrogen Impact Chlorella variabilis Productivity and Host Quality 0:87 Organic and Inorganic Nitrogen Impact Chlorella variabilis Productivity and Host Quality for Viral Production and Cell Lysis. 0:124 Organic and Inorganic Nitrogen Impact Chlorella variabilis Productivity and Host Quality for Viral Production and Cell Lysis. 25805020 0 75 theme Nitrogen 22:29 arg1 Productivity 59:70 Productivity 59:70 Productivity 59:70 Organic and Inorganic Nitrogen Impact Chlorella variabilis Productivity and Host Quality for Viral Production and Cell Lysis. 25805020 3 76 theme cells 657:661 arg1 virus 624:628 Chlorella virus 614:628 Chlorella virus 614:628 The concentration of yeast extract and presence of KNO3 in algae cultivation media were investigated to observe their effects on Chlorella variabilis NC64A physiology and composition and the subsequent effect on production of Chlorella virus and disruption of infected cells. 25805020 3 76 theme cells 657:661 arg1 disruption 634:643 disruption 634:643 disruption of infected cells 634:661 The concentration of yeast extract and presence of KNO3 in algae cultivation media were investigated to observe their effects on Chlorella variabilis NC64A physiology and composition and the subsequent effect on production of Chlorella virus and disruption of infected cells. 25805020 4 77 theme dry 748:750 arg1 weight 752:757 the total dry weight 738:757 the total dry weight 738:757 Cytoplasmic starch accumulation increased from 5% to approximately 35% of the total dry weight when yeast extract decreased from 1 to 0.25 g L(-1). 25805020 0 78 theme Chlorella 38:46 arg1 Quality 81:87 Host Quality 76:87 Host Quality 76:87 Organic and Inorganic Nitrogen Impact Chlorella variabilis Productivity and Host Quality for Viral Production and Cell Lysis. 25805020 0 78 theme Chlorella 38:46 arg1 variabilis 48:57 Organic and Inorganic Nitrogen Impact Chlorella variabilis Productivity and Host Quality 0:87 Organic and Inorganic Nitrogen Impact Chlorella variabilis Productivity and Host Quality for Viral Production and Cell Lysis. 0:124 Organic and Inorganic Nitrogen Impact Chlorella variabilis Productivity and Host Quality for Viral Production and Cell Lysis. 25805020 0 78 theme Chlorella 38:46 arg1 Productivity 59:70 Productivity 59:70 Productivity 59:70 Organic and Inorganic Nitrogen Impact Chlorella variabilis Productivity and Host Quality for Viral Production and Cell Lysis. 25805020 1 79 theme polysaccharides 296:310 arg1 utilization 269:279 utilization 269:279 utilization 269:279 Microalgae have been proposed as a potential feedstock for biofuel production; however, cell disruption is usually required for collection and utilization of cytoplasmic polysaccharides and lipids. 25805020 1 79 theme polysaccharides 296:310 arg1 collection 254:263 collection 254:263 collection 254:263 Microalgae have been proposed as a potential feedstock for biofuel production; however, cell disruption is usually required for collection and utilization of cytoplasmic polysaccharides and lipids. 25805020 5 80 theme 1.7 951:953 arg1 times 955:959 times 955:959 times 955:959 When cells were cultured with the lowest nitrogen levels, the total polysaccharide accounted for more than 50% of the cell wall, which was 1.7 times higher than the content in cells cultured with the highest nitrogen levels. 25805020 5 80 theme 1.7 951:953 arg1 wall 935:938 the cell wall 926:938 the cell wall 926:938 When cells were cultured with the lowest nitrogen levels, the total polysaccharide accounted for more than 50% of the cell wall, which was 1.7 times higher than the content in cells cultured with the highest nitrogen levels. 25805020 7 81 theme virus 1172:1176 arg1 infection 1178:1186 virus infection 1172:1186 virus infection 1172:1186 After virus infection, cells with a low C/N ratio produced a 7.6 times higher burst size than cells with a high C/N ratio, suggesting that the nitrogen content in C. variabilis has a large influence on viral production and cell lysis. 25805020 3 82 theme extract 415:421 arg1 presence 427:434 presence 427:434 presence 427:434 The concentration of yeast extract and presence of KNO3 in algae cultivation media were investigated to observe their effects on Chlorella variabilis NC64A physiology and composition and the subsequent effect on production of Chlorella virus and disruption of infected cells. 25805020 3 82 theme extract 415:421 arg1 concentration 392:404 The concentration 388:404 The concentration of yeast extract 388:421 The concentration of yeast extract and presence of KNO3 in algae cultivation media were investigated to observe their effects on Chlorella variabilis NC64A physiology and composition and the subsequent effect on production of Chlorella virus and disruption of infected cells. 25805020 4 83 theme g 803:803 arg1 L 805:805 1 to 0.25 g L 793:805 1 to 0.25 g L(-1) 793:809 Cytoplasmic starch accumulation increased from 5% to approximately 35% of the total dry weight when yeast extract decreased from 1 to 0.25 g L(-1). 25805020 4 83 theme g 803:803 arg1 -1 807:808 -1 807:808 -1 807:808 Cytoplasmic starch accumulation increased from 5% to approximately 35% of the total dry weight when yeast extract decreased from 1 to 0.25 g L(-1). 25805020 3 84 theme algae 447:451 arg1 media 465:469 algae cultivation media 447:469 algae cultivation media 447:469 The concentration of yeast extract and presence of KNO3 in algae cultivation media were investigated to observe their effects on Chlorella variabilis NC64A physiology and composition and the subsequent effect on production of Chlorella virus and disruption of infected cells. 25805020 1 85 theme lipids 316:321 arg1 utilization 269:279 utilization 269:279 utilization 269:279 Microalgae have been proposed as a potential feedstock for biofuel production; however, cell disruption is usually required for collection and utilization of cytoplasmic polysaccharides and lipids. 25805020 1 85 theme lipids 316:321 arg1 collection 254:263 collection 254:263 collection 254:263 Microalgae have been proposed as a potential feedstock for biofuel production; however, cell disruption is usually required for collection and utilization of cytoplasmic polysaccharides and lipids. 25805020 7 86 theme viral 1368:1372 arg1 production 1374:1383 viral production 1368:1383 viral production 1368:1383 After virus infection, cells with a low C/N ratio produced a 7.6 times higher burst size than cells with a high C/N ratio, suggesting that the nitrogen content in C. variabilis has a large influence on viral production and cell lysis. 25805020 5 87 theme wall 935:938 arg1 times 955:959 times 955:959 times 955:959 When cells were cultured with the lowest nitrogen levels, the total polysaccharide accounted for more than 50% of the cell wall, which was 1.7 times higher than the content in cells cultured with the highest nitrogen levels. 25805020 5 87 theme wall 935:938 arg1 wall 935:938 the cell wall 926:938 the cell wall 926:938 When cells were cultured with the lowest nitrogen levels, the total polysaccharide accounted for more than 50% of the cell wall, which was 1.7 times higher than the content in cells cultured with the highest nitrogen levels. 25805020 5 87 theme wall 935:938 arg1 % 921:921 more than 50% 909:921 more than 50% of the cell wall, which was 1.7 times higher than the content in cells cultured with the highest nitrogen levels 909:1034 When cells were cultured with the lowest nitrogen levels, the total polysaccharide accounted for more than 50% of the cell wall, which was 1.7 times higher than the content in cells cultured with the highest nitrogen levels. 25805020 3 88 theme Chlorella 517:525 arg1 physiology 544:553 Chlorella variabilis NC64A physiology 517:553 Chlorella variabilis NC64A physiology 517:553 The concentration of yeast extract and presence of KNO3 in algae cultivation media were investigated to observe their effects on Chlorella variabilis NC64A physiology and composition and the subsequent effect on production of Chlorella virus and disruption of infected cells. 25317120 2 0 theme similar 298:304 arg1 effects 306:312 similar effects 298:312 similar effects 298:312 Glutamine bound to the fibre may have similar effects once it has been liberated from the fibre in the colon. 25317120 13 1 theme viable 1916:1921 arg1 counts 1923:1928 viable counts 1916:1928 viable counts 1916:1928 CONCLUSIONS Although the probiotic strains survived and reached the caecum, except B. infantis CURE 21, there were no effects on viable counts or in the fermentation of different fibre components, but the formation of some bacterial metabolites decreased. 25317120 8 2 theme fibre 1044:1048 arg1 polymers 1050:1057 insoluble fibre polymers 1034:1057 insoluble fibre polymers (93%) 1034:1063 RESULTS The malt mostly contained insoluble fibre polymers (93%), consisting of glucose and xylose (38-41 g/kg) and some arabinose (21 g/kg). 25317120 8 2 theme fibre 1044:1048 arg1 % 1062:1062 93% 1060:1062 93% 1060:1062 RESULTS The malt mostly contained insoluble fibre polymers (93%), consisting of glucose and xylose (38-41 g/kg) and some arabinose (21 g/kg). 25317120 13 3 from effects 1905:1911 arg1 counts 1923:1928 viable counts 1916:1928 viable counts 1916:1928 CONCLUSIONS Although the probiotic strains survived and reached the caecum, except B. infantis CURE 21, there were no effects on viable counts or in the fermentation of different fibre components, but the formation of some bacterial metabolites decreased. 25317120 13 3 from effects 1905:1911 arg1 fermentation 1940:1951 the fermentation 1936:1951 the fermentation of different fibre components 1936:1981 CONCLUSIONS Although the probiotic strains survived and reached the caecum, except B. infantis CURE 21, there were no effects on viable counts or in the fermentation of different fibre components, but the formation of some bacterial metabolites decreased. 25317120 7 4 theme g/day 993:997 arg1 units 958:962 units 958:962 units 958:962 The daily dose of the probiotic strain was 1×10(9) colony forming units and the intake of fibre 0.82 g/day. 25317120 7 4 theme g/day 993:997 arg1 intake 972:977 the intake 968:977 the intake of fibre 0.82 g/day 968:997 The daily dose of the probiotic strain was 1×10(9) colony forming units and the intake of fibre 0.82 g/day. 25317120 7 5 theme fibre 982:986 arg1 g/day 993:997 fibre 0.82 g/day 982:997 fibre 0.82 g/day 982:997 The daily dose of the probiotic strain was 1×10(9) colony forming units and the intake of fibre 0.82 g/day. 25317120 3 6 from amounts 417:423 arg1 barley 435:440 malted barley 428:440 malted barley 428:440 Both β-glucans and glutamine are found in high amounts in malted barley. 25317120 8 7 contain contained 1024:1032 arg2 polymers 1050:1057 insoluble fibre polymers 1034:1057 insoluble fibre polymers (93%) 1034:1063 RESULTS The malt mostly contained insoluble fibre polymers (93%), consisting of glucose and xylose (38-41 g/kg) and some arabinose (21 g/kg). 25317120 8 7 contain contained 1024:1032 arg1 malt 1012:1015 The malt 1008:1015 The malt 1008:1015 RESULTS The malt mostly contained insoluble fibre polymers (93%), consisting of glucose and xylose (38-41 g/kg) and some arabinose (21 g/kg). 25317120 8 7 contain contained 1024:1032 arg2 % 1062:1062 93% 1060:1062 93% 1060:1062 RESULTS The malt mostly contained insoluble fibre polymers (93%), consisting of glucose and xylose (38-41 g/kg) and some arabinose (21 g/kg). 25317120 10 8 theme plantarum 1381:1389 arg1 HEAL 1391:1394 L. plantarum HEAL 9 and L. rhamnosus 271 1378:1417 HEAL 1391:1394 Caecal and portal levels of acetic acid decreased in the rats after the addition of L. plantarum HEAL 9 and L. rhamnosus 271, and also the levels of butyric acid. 25317120 11 9 theme Lactobacilli 1577:1588 arg1 composition 1562:1572 the caecal composition 1551:1572 the caecal composition of Lactobacilli 1551:1588 Viable counts of Lactobacillus, Bifidobacterium and Enterobacteriaceae were unaffected, while the caecal composition of Lactobacilli was influenced by the type of strain administrated. 25317120 7 10 theme strain 924:929 arg1 dose 902:905 The daily dose 892:905 The daily dose of the probiotic strain 892:929 The daily dose of the probiotic strain was 1×10(9) colony forming units and the intake of fibre 0.82 g/day. 25317120 7 10 theme strain 924:929 arg1 colony 943:948 1×10(9) colony 935:948 1×10(9) colony forming units and the intake of fibre 0.82 g/day 935:997 The daily dose of the probiotic strain was 1×10(9) colony forming units and the intake of fibre 0.82 g/day. 25317120 10 11 theme L. 1402:1403 arg1 addition 1366:1373 the addition 1362:1373 the addition of L. plantarum HEAL 9 and L. rhamnosus 271, and also the levels of butyric acid 1362:1454 Caecal and portal levels of acetic acid decreased in the rats after the addition of L. plantarum HEAL 9 and L. rhamnosus 271, and also the levels of butyric acid. 25317120 13 12 theme infantis 1873:1880 arg1 CURE 1882:1885 B. infantis CURE 21 1870:1888 B. infantis CURE 21 1870:1888 CONCLUSIONS Although the probiotic strains survived and reached the caecum, except B. infantis CURE 21, there were no effects on viable counts or in the fermentation of different fibre components, but the formation of some bacterial metabolites decreased. 25317120 5 13 from acids 768:772 arg1 caecum 791:796 caecum 791:796 caecum 791:796 OBJECTIVE To investigate whether Lactobacillus rhamnosus 271, Lactobacillus paracasei 87002, Lactobacillus plantarum HEAL 9 and 19, and Bifidobacterium infantis CURE 21 affect the levels of short-chain fatty acids and glutamine in caecum and portal blood of rats fed barley malt. 25317120 5 13 from acids 768:772 arg1 blood 809:813 portal blood 802:813 portal blood 802:813 OBJECTIVE To investigate whether Lactobacillus rhamnosus 271, Lactobacillus paracasei 87002, Lactobacillus plantarum HEAL 9 and 19, and Bifidobacterium infantis CURE 21 affect the levels of short-chain fatty acids and glutamine in caecum and portal blood of rats fed barley malt. 25317120 6 14 theme experimental 851:862 arg1 diets 864:868 The experimental diets 847:868 DESIGN The experimental diets 840:868 DESIGN The experimental diets were fed for 12 days. 25317120 14 15 theme insoluble 2085:2093 arg1 fibres 2095:2100 insoluble fibres 2085:2100 insoluble fibres 2085:2100 This may be due to the high proportion of insoluble fibres in the malt. 25317120 5 16 dep Lactobacillus 653:665 arg1 HEAL 677:680 HEAL 677:680 HEAL 677:680 OBJECTIVE To investigate whether Lactobacillus rhamnosus 271, Lactobacillus paracasei 87002, Lactobacillus plantarum HEAL 9 and 19, and Bifidobacterium infantis CURE 21 affect the levels of short-chain fatty acids and glutamine in caecum and portal blood of rats fed barley malt. 25317120 5 16 dep Lactobacillus 653:665 arg1 19 688:689 19 688:689 19 688:689 OBJECTIVE To investigate whether Lactobacillus rhamnosus 271, Lactobacillus paracasei 87002, Lactobacillus plantarum HEAL 9 and 19, and Bifidobacterium infantis CURE 21 affect the levels of short-chain fatty acids and glutamine in caecum and portal blood of rats fed barley malt. 25317120 5 16 dep Lactobacillus 653:665 arg1 plantarum 667:675 Lactobacillus plantarum HEAL 9 and 19 653:689 Lactobacillus plantarum HEAL 9 and 19 653:689 OBJECTIVE To investigate whether Lactobacillus rhamnosus 271, Lactobacillus paracasei 87002, Lactobacillus plantarum HEAL 9 and 19, and Bifidobacterium infantis CURE 21 affect the levels of short-chain fatty acids and glutamine in caecum and portal blood of rats fed barley malt. 25317120 5 17 theme fatty 762:766 arg1 acids 768:772 short-chain fatty acids 750:772 short-chain fatty acids 750:772 OBJECTIVE To investigate whether Lactobacillus rhamnosus 271, Lactobacillus paracasei 87002, Lactobacillus plantarum HEAL 9 and 19, and Bifidobacterium infantis CURE 21 affect the levels of short-chain fatty acids and glutamine in caecum and portal blood of rats fed barley malt. 25317120 5 18 from caecum 791:796 arg1 levels 740:745 the levels 736:745 the levels of short-chain fatty acids and glutamine in caecum and portal blood of rats fed barley malt 736:837 OBJECTIVE To investigate whether Lactobacillus rhamnosus 271, Lactobacillus paracasei 87002, Lactobacillus plantarum HEAL 9 and 19, and Bifidobacterium infantis CURE 21 affect the levels of short-chain fatty acids and glutamine in caecum and portal blood of rats fed barley malt. 25317120 5 19 theme rats 818:821 arg1 caecum 791:796 caecum 791:796 caecum 791:796 OBJECTIVE To investigate whether Lactobacillus rhamnosus 271, Lactobacillus paracasei 87002, Lactobacillus plantarum HEAL 9 and 19, and Bifidobacterium infantis CURE 21 affect the levels of short-chain fatty acids and glutamine in caecum and portal blood of rats fed barley malt. 25317120 5 19 theme rats 818:821 arg1 blood 809:813 portal blood 802:813 portal blood 802:813 OBJECTIVE To investigate whether Lactobacillus rhamnosus 271, Lactobacillus paracasei 87002, Lactobacillus plantarum HEAL 9 and 19, and Bifidobacterium infantis CURE 21 affect the levels of short-chain fatty acids and glutamine in caecum and portal blood of rats fed barley malt. 25317120 2 20 from colon 363:367 arg1 fibre 350:354 fibre 350:354 fibre 350:354 Glutamine bound to the fibre may have similar effects once it has been liberated from the fibre in the colon. 25317120 0 21 theme selected 63:70 arg1 strains 81:87 selected bacteria strains 63:87 selected bacteria strains 63:87 Prebiotic and synbiotic effects on rats fed malted barley with selected bacteria strains. 25317120 9 22 from rats 1212:1215 arg1 resistant 1179:1187 resistant 1179:1187 resistant 1179:1187 The fibre polysaccharides were quite resistant to fermentation in the rats, regardless of whether or not probiotics were added (25-30% were fermented). 25317120 9 22 from rats 1212:1215 arg1 polysaccharides 1152:1166 The fibre polysaccharides 1142:1166 The fibre polysaccharides 1142:1166 The fibre polysaccharides were quite resistant to fermentation in the rats, regardless of whether or not probiotics were added (25-30% were fermented). 25317120 3 23 located found 403:407 arg1 amounts 417:423 high amounts 412:423 high amounts in malted barley 412:440 Both β-glucans and glutamine are found in high amounts in malted barley. 25317120 3 23 located found 403:407 arg2 glutamine 389:397 glutamine 389:397 glutamine 389:397 Both β-glucans and glutamine are found in high amounts in malted barley. 25317120 3 23 located found 403:407 arg2 β-glucans 375:383 β-glucans 375:383 β-glucans 375:383 Both β-glucans and glutamine are found in high amounts in malted barley. 25317120 5 24 theme barley 827:832 arg1 malt 834:837 barley malt 827:837 barley malt 827:837 OBJECTIVE To investigate whether Lactobacillus rhamnosus 271, Lactobacillus paracasei 87002, Lactobacillus plantarum HEAL 9 and 19, and Bifidobacterium infantis CURE 21 affect the levels of short-chain fatty acids and glutamine in caecum and portal blood of rats fed barley malt. 25317120 12 25 theme L. 1719:1720 arg1 HEAL 1732:1735 L. plantarum HEAL 9 and 19 1719:1744 HEAL 1732:1735 Portal levels of glutamine were unchanged, but glycine levels increased with L. plantarum HEAL 9 and 19 and phenylalanine with L. rhamnosus 271. 25317120 10 26 theme levels 1433:1438 arg1 addition 1366:1373 the addition 1362:1373 the addition of L. plantarum HEAL 9 and L. rhamnosus 271, and also the levels of butyric acid 1362:1454 Caecal and portal levels of acetic acid decreased in the rats after the addition of L. plantarum HEAL 9 and L. rhamnosus 271, and also the levels of butyric acid. 25317120 9 27 theme fibre 1146:1150 arg1 resistant 1179:1187 resistant 1179:1187 resistant 1179:1187 The fibre polysaccharides were quite resistant to fermentation in the rats, regardless of whether or not probiotics were added (25-30% were fermented). 25317120 9 27 theme fibre 1146:1150 arg1 polysaccharides 1152:1166 The fibre polysaccharides 1142:1166 The fibre polysaccharides 1142:1166 The fibre polysaccharides were quite resistant to fermentation in the rats, regardless of whether or not probiotics were added (25-30% were fermented). 25317120 0 28 theme Prebiotic 0:8 arg1 effects 24:30 Prebiotic and synbiotic effects 0:30 Prebiotic and synbiotic effects on rats 0:38 Prebiotic and synbiotic effects on rats fed malted barley with selected bacteria strains. 25317120 12 29 theme glycine 1689:1695 arg1 levels 1697:1702 glycine levels 1689:1702 glycine levels 1689:1702 Portal levels of glutamine were unchanged, but glycine levels increased with L. plantarum HEAL 9 and 19 and phenylalanine with L. rhamnosus 271. 25317120 0 30 theme synbiotic 14:22 arg1 effects 24:30 Prebiotic and synbiotic effects 0:30 Prebiotic and synbiotic effects on rats 0:38 Prebiotic and synbiotic effects on rats fed malted barley with selected bacteria strains. 25317120 1 31 theme colonic 244:250 arg1 health 252:257 colonic health 244:257 colonic health 244:257 BACKGROUND Butyric acid, one of the key products formed when β-glucans are degraded by the microbiota in the colon, has been proposed to be important for colonic health. 25317120 1 32 theme Butyric 101:107 arg1 one 115:117 one 115:117 one 115:117 BACKGROUND Butyric acid, one of the key products formed when β-glucans are degraded by the microbiota in the colon, has been proposed to be important for colonic health. 25317120 1 32 theme Butyric 101:107 arg1 acid 109:112 BACKGROUND Butyric acid 90:112 BACKGROUND Butyric acid 90:112 BACKGROUND Butyric acid, one of the key products formed when β-glucans are degraded by the microbiota in the colon, has been proposed to be important for colonic health. 25317120 1 32 theme Butyric 101:107 arg1 products 130:137 the key products 122:137 the key products formed when β-glucans are degraded by the microbiota in the colon 122:203 BACKGROUND Butyric acid, one of the key products formed when β-glucans are degraded by the microbiota in the colon, has been proposed to be important for colonic health. 25317120 11 33 theme Lactobacillus 1474:1486 arg1 counts 1464:1469 Viable counts 1457:1469 Viable counts of Lactobacillus, Bifidobacterium and Enterobacteriaceae 1457:1526 Viable counts of Lactobacillus, Bifidobacterium and Enterobacteriaceae were unaffected, while the caecal composition of Lactobacilli was influenced by the type of strain administrated. 25317120 10 34 theme butyric 1443:1449 arg1 acid 1451:1454 butyric acid 1443:1454 butyric acid 1443:1454 Caecal and portal levels of acetic acid decreased in the rats after the addition of L. plantarum HEAL 9 and L. rhamnosus 271, and also the levels of butyric acid. 25317120 4 35 dep Lactobacillus 443:455 arg1 rhamnosus 457:465 Lactobacillus rhamnosus 443:465 Lactobacillus rhamnosus together with malt 443:484 Lactobacillus rhamnosus together with malt has been shown to increase the formation of butyric acid further in rats. 25317120 13 36 theme different 1956:1964 arg1 components 1972:1981 different fibre components 1956:1981 different fibre components 1956:1981 CONCLUSIONS Although the probiotic strains survived and reached the caecum, except B. infantis CURE 21, there were no effects on viable counts or in the fermentation of different fibre components, but the formation of some bacterial metabolites decreased. 25317120 13 37 theme components 1972:1981 arg1 fermentation 1940:1951 the fermentation 1936:1951 the fermentation of different fibre components 1936:1981 CONCLUSIONS Although the probiotic strains survived and reached the caecum, except B. infantis CURE 21, there were no effects on viable counts or in the fermentation of different fibre components, but the formation of some bacterial metabolites decreased. 25317120 2 38 attach liberated 331:339 arg2 it 319:320 it 319:320 it 319:320 Glutamine bound to the fibre may have similar effects once it has been liberated from the fibre in the colon. 25317120 2 38 attach liberated 331:339 arg1 fibre 350:354 fibre 350:354 fibre 350:354 Glutamine bound to the fibre may have similar effects once it has been liberated from the fibre in the colon. 25317120 14 39 from proportion 2071:2080 arg1 malt 2109:2112 the malt 2105:2112 the malt 2105:2112 This may be due to the high proportion of insoluble fibres in the malt. 25317120 10 40 theme acetic 1322:1327 arg1 acid 1329:1332 acetic acid 1322:1332 acetic acid 1322:1332 Caecal and portal levels of acetic acid decreased in the rats after the addition of L. plantarum HEAL 9 and L. rhamnosus 271, and also the levels of butyric acid. 25317120 11 41 theme Enterobacteriaceae 1509:1526 arg1 counts 1464:1469 Viable counts 1457:1469 Viable counts of Lactobacillus, Bifidobacterium and Enterobacteriaceae 1457:1526 Viable counts of Lactobacillus, Bifidobacterium and Enterobacteriaceae were unaffected, while the caecal composition of Lactobacilli was influenced by the type of strain administrated. 25317120 12 42 theme Portal 1642:1647 arg1 levels 1649:1654 Portal levels 1642:1654 Portal levels of glutamine 1642:1667 Portal levels of glutamine were unchanged, but glycine levels increased with L. plantarum HEAL 9 and 19 and phenylalanine with L. rhamnosus 271. 25317120 2 43 from fibre 350:354 arg1 colon 363:367 the colon 359:367 the colon 359:367 Glutamine bound to the fibre may have similar effects once it has been liberated from the fibre in the colon. 25317120 1 44 theme key 126:128 arg1 products 130:137 the key products 122:137 the key products formed when β-glucans are degraded by the microbiota in the colon 122:203 BACKGROUND Butyric acid, one of the key products formed when β-glucans are degraded by the microbiota in the colon, has been proposed to be important for colonic health. 25317120 4 45 theme butyric 530:536 arg1 acid 538:541 butyric acid 530:541 butyric acid 530:541 Lactobacillus rhamnosus together with malt has been shown to increase the formation of butyric acid further in rats. 25317120 11 46 theme Bifidobacterium 1489:1503 arg1 counts 1464:1469 Viable counts 1457:1469 Viable counts of Lactobacillus, Bifidobacterium and Enterobacteriaceae 1457:1526 Viable counts of Lactobacillus, Bifidobacterium and Enterobacteriaceae were unaffected, while the caecal composition of Lactobacilli was influenced by the type of strain administrated. 25317120 13 47 theme bacterial 2010:2018 arg1 metabolites 2020:2030 some bacterial metabolites 2005:2030 some bacterial metabolites 2005:2030 CONCLUSIONS Although the probiotic strains survived and reached the caecum, except B. infantis CURE 21, there were no effects on viable counts or in the fermentation of different fibre components, but the formation of some bacterial metabolites decreased. 25317120 5 48 theme Bifidobacterium 696:710 arg1 CURE 721:724 Bifidobacterium infantis CURE 21 696:727 Bifidobacterium infantis CURE 21 696:727 OBJECTIVE To investigate whether Lactobacillus rhamnosus 271, Lactobacillus paracasei 87002, Lactobacillus plantarum HEAL 9 and 19, and Bifidobacterium infantis CURE 21 affect the levels of short-chain fatty acids and glutamine in caecum and portal blood of rats fed barley malt. 25317120 3 49 theme malted 428:433 arg1 barley 435:440 malted barley 428:440 malted barley 428:440 Both β-glucans and glutamine are found in high amounts in malted barley. 25317120 10 50 theme L. 1378:1379 arg1 HEAL 1391:1394 L. plantarum HEAL 9 and L. rhamnosus 271 1378:1417 HEAL 1391:1394 Caecal and portal levels of acetic acid decreased in the rats after the addition of L. plantarum HEAL 9 and L. rhamnosus 271, and also the levels of butyric acid. 25317120 8 51 theme insoluble 1034:1042 arg1 polymers 1050:1057 insoluble fibre polymers 1034:1057 insoluble fibre polymers (93%) 1034:1063 RESULTS The malt mostly contained insoluble fibre polymers (93%), consisting of glucose and xylose (38-41 g/kg) and some arabinose (21 g/kg). 25317120 8 51 theme insoluble 1034:1042 arg1 % 1062:1062 93% 1060:1062 93% 1060:1062 RESULTS The malt mostly contained insoluble fibre polymers (93%), consisting of glucose and xylose (38-41 g/kg) and some arabinose (21 g/kg). 25317120 13 52 theme metabolites 2020:2030 arg1 formation 1992:2000 the formation 1988:2000 the formation of some bacterial metabolites 1988:2030 CONCLUSIONS Although the probiotic strains survived and reached the caecum, except B. infantis CURE 21, there were no effects on viable counts or in the fermentation of different fibre components, but the formation of some bacterial metabolites decreased. 25317120 6 53 dep DESIGN 840:845 arg1 diets 864:868 The experimental diets 847:868 DESIGN The experimental diets 840:868 DESIGN The experimental diets were fed for 12 days. 25317120 0 54 with barley 51:56 arg1 strains 81:87 selected bacteria strains 63:87 selected bacteria strains 63:87 Prebiotic and synbiotic effects on rats fed malted barley with selected bacteria strains. 25317120 8 55 dep RESULTS 1000:1006 arg1 contained 1024:1032 contained 1024:1032 contained insoluble fibre polymers (93%), consisting of glucose and xylose (38-41 g/kg) and some arabinose (21 g/kg) 1024:1139 RESULTS The malt mostly contained insoluble fibre polymers (93%), consisting of glucose and xylose (38-41 g/kg) and some arabinose (21 g/kg). 25317120 5 56 theme infantis 712:719 arg1 CURE 721:724 Bifidobacterium infantis CURE 21 696:727 Bifidobacterium infantis CURE 21 696:727 OBJECTIVE To investigate whether Lactobacillus rhamnosus 271, Lactobacillus paracasei 87002, Lactobacillus plantarum HEAL 9 and 19, and Bifidobacterium infantis CURE 21 affect the levels of short-chain fatty acids and glutamine in caecum and portal blood of rats fed barley malt. 25317120 5 57 theme portal 802:807 arg1 blood 809:813 portal blood 802:813 portal blood 802:813 OBJECTIVE To investigate whether Lactobacillus rhamnosus 271, Lactobacillus paracasei 87002, Lactobacillus plantarum HEAL 9 and 19, and Bifidobacterium infantis CURE 21 affect the levels of short-chain fatty acids and glutamine in caecum and portal blood of rats fed barley malt. 25317120 5 58 from glutamine 778:786 arg1 caecum 791:796 caecum 791:796 caecum 791:796 OBJECTIVE To investigate whether Lactobacillus rhamnosus 271, Lactobacillus paracasei 87002, Lactobacillus plantarum HEAL 9 and 19, and Bifidobacterium infantis CURE 21 affect the levels of short-chain fatty acids and glutamine in caecum and portal blood of rats fed barley malt. 25317120 5 58 from glutamine 778:786 arg1 blood 809:813 portal blood 802:813 portal blood 802:813 OBJECTIVE To investigate whether Lactobacillus rhamnosus 271, Lactobacillus paracasei 87002, Lactobacillus plantarum HEAL 9 and 19, and Bifidobacterium infantis CURE 21 affect the levels of short-chain fatty acids and glutamine in caecum and portal blood of rats fed barley malt. 25317120 10 59 theme HEAL 1391:1394 arg1 addition 1366:1373 the addition 1362:1373 the addition of L. plantarum HEAL 9 and L. rhamnosus 271, and also the levels of butyric acid 1362:1454 Caecal and portal levels of acetic acid decreased in the rats after the addition of L. plantarum HEAL 9 and L. rhamnosus 271, and also the levels of butyric acid. 25317120 5 60 theme acids 768:772 arg1 levels 740:745 the levels 736:745 the levels of short-chain fatty acids and glutamine in caecum and portal blood of rats fed barley malt 736:837 OBJECTIVE To investigate whether Lactobacillus rhamnosus 271, Lactobacillus paracasei 87002, Lactobacillus plantarum HEAL 9 and 19, and Bifidobacterium infantis CURE 21 affect the levels of short-chain fatty acids and glutamine in caecum and portal blood of rats fed barley malt. 25317120 5 61 theme glutamine 778:786 arg1 levels 740:745 the levels 736:745 the levels of short-chain fatty acids and glutamine in caecum and portal blood of rats fed barley malt 736:837 OBJECTIVE To investigate whether Lactobacillus rhamnosus 271, Lactobacillus paracasei 87002, Lactobacillus plantarum HEAL 9 and 19, and Bifidobacterium infantis CURE 21 affect the levels of short-chain fatty acids and glutamine in caecum and portal blood of rats fed barley malt. 25317120 11 62 theme strain 1620:1625 arg1 type 1612:1615 the type 1608:1615 the type of strain administrated 1608:1639 Viable counts of Lactobacillus, Bifidobacterium and Enterobacteriaceae were unaffected, while the caecal composition of Lactobacilli was influenced by the type of strain administrated. 25317120 13 63 theme B. 1870:1871 arg1 CURE 1882:1885 B. infantis CURE 21 1870:1888 B. infantis CURE 21 1870:1888 CONCLUSIONS Although the probiotic strains survived and reached the caecum, except B. infantis CURE 21, there were no effects on viable counts or in the fermentation of different fibre components, but the formation of some bacterial metabolites decreased. 25317120 14 64 theme fibres 2095:2100 arg1 proportion 2071:2080 the high proportion 2062:2080 the high proportion of insoluble fibres in the malt 2062:2112 This may be due to the high proportion of insoluble fibres in the malt. 25317120 7 65 theme probiotic 914:922 arg1 strain 924:929 the probiotic strain 910:929 the probiotic strain 910:929 The daily dose of the probiotic strain was 1×10(9) colony forming units and the intake of fibre 0.82 g/day. 25317120 5 66 from blood 809:813 arg1 levels 740:745 the levels 736:745 the levels of short-chain fatty acids and glutamine in caecum and portal blood of rats fed barley malt 736:837 OBJECTIVE To investigate whether Lactobacillus rhamnosus 271, Lactobacillus paracasei 87002, Lactobacillus plantarum HEAL 9 and 19, and Bifidobacterium infantis CURE 21 affect the levels of short-chain fatty acids and glutamine in caecum and portal blood of rats fed barley malt. 25317120 0 67 from effects 24:30 arg1 rats 35:38 rats 35:38 rats 35:38 Prebiotic and synbiotic effects on rats fed malted barley with selected bacteria strains. 25317120 14 68 theme high 2066:2069 arg1 proportion 2071:2080 the high proportion 2062:2080 the high proportion of insoluble fibres in the malt 2062:2112 This may be due to the high proportion of insoluble fibres in the malt. 25317120 0 69 theme bacteria 72:79 arg1 strains 81:87 selected bacteria strains 63:87 selected bacteria strains 63:87 Prebiotic and synbiotic effects on rats fed malted barley with selected bacteria strains. 25317120 7 70 theme daily 896:900 arg1 dose 902:905 The daily dose 892:905 The daily dose of the probiotic strain 892:929 The daily dose of the probiotic strain was 1×10(9) colony forming units and the intake of fibre 0.82 g/day. 25317120 7 70 theme daily 896:900 arg1 colony 943:948 1×10(9) colony 935:948 1×10(9) colony forming units and the intake of fibre 0.82 g/day 935:997 The daily dose of the probiotic strain was 1×10(9) colony forming units and the intake of fibre 0.82 g/day. 25317120 1 71 theme products 130:137 arg1 one 115:117 one 115:117 one 115:117 BACKGROUND Butyric acid, one of the key products formed when β-glucans are degraded by the microbiota in the colon, has been proposed to be important for colonic health. 25317120 1 71 theme products 130:137 arg1 acid 109:112 BACKGROUND Butyric acid 90:112 BACKGROUND Butyric acid 90:112 BACKGROUND Butyric acid, one of the key products formed when β-glucans are degraded by the microbiota in the colon, has been proposed to be important for colonic health. 25317120 1 71 theme products 130:137 arg1 products 130:137 the key products 122:137 the key products formed when β-glucans are degraded by the microbiota in the colon 122:203 BACKGROUND Butyric acid, one of the key products formed when β-glucans are degraded by the microbiota in the colon, has been proposed to be important for colonic health. 25317120 2 72 contain have 293:296 arg1 Glutamine 260:268 Glutamine 260:268 Glutamine bound to the fibre 260:287 Glutamine bound to the fibre may have similar effects once it has been liberated from the fibre in the colon. 25317120 2 72 contain have 293:296 arg2 effects 306:312 similar effects 298:312 similar effects 298:312 Glutamine bound to the fibre may have similar effects once it has been liberated from the fibre in the colon. 25317120 12 73 theme plantarum 1722:1730 arg1 HEAL 1732:1735 L. plantarum HEAL 9 and 19 1719:1744 HEAL 1732:1735 Portal levels of glutamine were unchanged, but glycine levels increased with L. plantarum HEAL 9 and 19 and phenylalanine with L. rhamnosus 271. 25317120 11 74 theme caecal 1555:1560 arg1 composition 1562:1572 the caecal composition 1551:1572 the caecal composition of Lactobacilli 1551:1588 Viable counts of Lactobacillus, Bifidobacterium and Enterobacteriaceae were unaffected, while the caecal composition of Lactobacilli was influenced by the type of strain administrated. 25317120 9 75 from resistant 1179:1187 arg1 rats 1212:1215 the rats 1208:1215 the rats 1208:1215 The fibre polysaccharides were quite resistant to fermentation in the rats, regardless of whether or not probiotics were added (25-30% were fermented). 25317120 5 76 theme short-chain 750:760 arg1 acids 768:772 short-chain fatty acids 750:772 short-chain fatty acids 750:772 OBJECTIVE To investigate whether Lactobacillus rhamnosus 271, Lactobacillus paracasei 87002, Lactobacillus plantarum HEAL 9 and 19, and Bifidobacterium infantis CURE 21 affect the levels of short-chain fatty acids and glutamine in caecum and portal blood of rats fed barley malt. 25317120 12 77 theme glutamine 1659:1667 arg1 levels 1649:1654 Portal levels 1642:1654 Portal levels of glutamine 1642:1667 Portal levels of glutamine were unchanged, but glycine levels increased with L. plantarum HEAL 9 and 19 and phenylalanine with L. rhamnosus 271. 25317120 1 78 theme BACKGROUND 90:99 arg1 one 115:117 one 115:117 one 115:117 BACKGROUND Butyric acid, one of the key products formed when β-glucans are degraded by the microbiota in the colon, has been proposed to be important for colonic health. 25317120 1 78 theme BACKGROUND 90:99 arg1 acid 109:112 BACKGROUND Butyric acid 90:112 BACKGROUND Butyric acid 90:112 BACKGROUND Butyric acid, one of the key products formed when β-glucans are degraded by the microbiota in the colon, has been proposed to be important for colonic health. 25317120 1 78 theme BACKGROUND 90:99 arg1 products 130:137 the key products 122:137 the key products formed when β-glucans are degraded by the microbiota in the colon 122:203 BACKGROUND Butyric acid, one of the key products formed when β-glucans are degraded by the microbiota in the colon, has been proposed to be important for colonic health. 25317120 10 79 theme portal 1305:1310 arg1 levels 1312:1317 Caecal and portal levels 1294:1317 Caecal and portal levels of acetic acid 1294:1332 Caecal and portal levels of acetic acid decreased in the rats after the addition of L. plantarum HEAL 9 and L. rhamnosus 271, and also the levels of butyric acid. 25317120 10 80 theme acid 1451:1454 arg1 levels 1433:1438 the levels 1429:1438 the levels of butyric acid 1429:1454 Caecal and portal levels of acetic acid decreased in the rats after the addition of L. plantarum HEAL 9 and L. rhamnosus 271, and also the levels of butyric acid. 25317120 10 81 theme Caecal 1294:1299 arg1 levels 1312:1317 Caecal and portal levels 1294:1317 Caecal and portal levels of acetic acid 1294:1332 Caecal and portal levels of acetic acid decreased in the rats after the addition of L. plantarum HEAL 9 and L. rhamnosus 271, and also the levels of butyric acid. 25317120 11 82 theme Viable 1457:1462 arg1 counts 1464:1469 Viable counts 1457:1469 Viable counts of Lactobacillus, Bifidobacterium and Enterobacteriaceae 1457:1526 Viable counts of Lactobacillus, Bifidobacterium and Enterobacteriaceae were unaffected, while the caecal composition of Lactobacilli was influenced by the type of strain administrated. 25317120 0 83 theme malted 44:49 arg1 barley 51:56 malted barley 44:56 malted barley with selected bacteria strains 44:87 Prebiotic and synbiotic effects on rats fed malted barley with selected bacteria strains. 25317120 13 84 theme fibre 1966:1970 arg1 components 1972:1981 different fibre components 1956:1981 different fibre components 1956:1981 CONCLUSIONS Although the probiotic strains survived and reached the caecum, except B. infantis CURE 21, there were no effects on viable counts or in the fermentation of different fibre components, but the formation of some bacterial metabolites decreased. 25317120 5 85 from levels 740:745 arg1 caecum 791:796 caecum 791:796 caecum 791:796 OBJECTIVE To investigate whether Lactobacillus rhamnosus 271, Lactobacillus paracasei 87002, Lactobacillus plantarum HEAL 9 and 19, and Bifidobacterium infantis CURE 21 affect the levels of short-chain fatty acids and glutamine in caecum and portal blood of rats fed barley malt. 25317120 5 85 from levels 740:745 arg1 blood 809:813 portal blood 802:813 portal blood 802:813 OBJECTIVE To investigate whether Lactobacillus rhamnosus 271, Lactobacillus paracasei 87002, Lactobacillus plantarum HEAL 9 and 19, and Bifidobacterium infantis CURE 21 affect the levels of short-chain fatty acids and glutamine in caecum and portal blood of rats fed barley malt. 25317120 10 86 theme acid 1329:1332 arg1 levels 1312:1317 Caecal and portal levels 1294:1317 Caecal and portal levels of acetic acid 1294:1332 Caecal and portal levels of acetic acid decreased in the rats after the addition of L. plantarum HEAL 9 and L. rhamnosus 271, and also the levels of butyric acid. 25317120 13 87 theme probiotic 1812:1820 arg1 strains 1822:1828 the probiotic strains 1808:1828 the probiotic strains 1808:1828 CONCLUSIONS Although the probiotic strains survived and reached the caecum, except B. infantis CURE 21, there were no effects on viable counts or in the fermentation of different fibre components, but the formation of some bacterial metabolites decreased. 25317120 4 88 theme acid 538:541 arg1 formation 517:525 the formation 513:525 the formation of butyric acid 513:541 Lactobacillus rhamnosus together with malt has been shown to increase the formation of butyric acid further in rats. 25317120 1 89 from microbiota 181:190 arg1 colon 199:203 the colon 195:203 the colon 195:203 BACKGROUND Butyric acid, one of the key products formed when β-glucans are degraded by the microbiota in the colon, has been proposed to be important for colonic health. 25317120 3 90 theme high 412:415 arg1 amounts 417:423 high amounts 412:423 high amounts in malted barley 412:440 Both β-glucans and glutamine are found in high amounts in malted barley. 25123433 5 0 theme computational 632:644 arg1 method 646:651 an accurate computational method 620:651 an accurate computational method named PECM 620:662 In this paper, an accurate computational method named PECM is proposed for identifying ECMs. 25123433 7 1 theme information 921:931 arg1 redundancy 933:942 information redundancy 921:942 information redundancy 921:942 Rather than simply combining the features which may bring information redundancy and unwanted noises, we use Fisher-Markov selector and incremental feature selection approach to search the optimal feature subsets. 25123433 2 2 gly glycoproteins 280:292 arg1 glycoproteins 280:292 glycoproteins 280:292 glycoproteins 280:292 They consist of various secreted proteins, mainly polysaccharides and glycoproteins. 25123433 6 3 theme physicochemical 835:849 arg1 properties 851:860 physicochemical properties 835:860 physicochemical properties 835:860 Here, we explore various sequence-derived discriminative features including evolutionary information, predicted secondary structure, and physicochemical properties. 25123433 10 4 from http 1426:1429 arg1 PECM 1359:1362 A web-server named PECM 1340:1362 A web-server named PECM which implements the proposed approach 1340:1401 A web-server named PECM which implements the proposed approach is freely available at http://59.73.198.144:8088/PECM/. 25123433 10 4 from http 1426:1429 arg1 available 1413:1421 available 1413:1421 available 1413:1421 A web-server named PECM which implements the proposed approach is freely available at http://59.73.198.144:8088/PECM/. 25123433 4 5 theme therapeutic 562:572 arg1 targets 574:580 therapeutic targets 562:580 therapeutic targets 562:580 Accurate identification of ECMs is a significant step in understanding the evolution of cancer as well as promises wide range of potential applications in therapeutic targets or diagnostic markers. 25123433 0 6 theme pseudo 78:83 arg1 composition 96:106 Chou's pseudo amino acid composition 71:106 Chou's pseudo amino acid composition 71:106 PECM: prediction of extracellular matrix proteins using the concept of Chou's pseudo amino acid composition. 25123433 7 7 theme Fisher-Markov 972:984 arg1 selector 986:993 Fisher-Markov selector and incremental feature selection approach 972:1036 selector 986:993 Rather than simply combining the features which may bring information redundancy and unwanted noises, we use Fisher-Markov selector and incremental feature selection approach to search the optimal feature subsets. 25123433 7 8 theme feature 1011:1017 arg1 approach 1029:1036 Fisher-Markov selector and incremental feature selection approach 972:1036 approach 1029:1036 Rather than simply combining the features which may bring information redundancy and unwanted noises, we use Fisher-Markov selector and incremental feature selection approach to search the optimal feature subsets. 25123433 9 9 with competitive 1279:1289 arg1 tools 1333:1337 the state-of-the-art ECMs prediction tools 1296:1337 the state-of-the-art ECMs prediction tools 1296:1337 PECM achieves good prediction performance with the ACC scores about 86% and 90% on testing and independent datasets, which are competitive with the state-of-the-art ECMs prediction tools. 25123433 4 10 theme diagnostic 585:594 arg1 markers 596:602 diagnostic markers 585:602 diagnostic markers 585:602 Accurate identification of ECMs is a significant step in understanding the evolution of cancer as well as promises wide range of potential applications in therapeutic targets or diagnostic markers. 25123433 3 11 theme information 342:352 arg1 exchange 316:323 the exchange 312:323 the exchange of materials and information between resident cells and the external environment 312:404 The ECMs involve the exchange of materials and information between resident cells and the external environment. 25123433 9 12 theme state-of-the-art 1300:1315 arg1 tools 1333:1337 the state-of-the-art ECMs prediction tools 1296:1337 the state-of-the-art ECMs prediction tools 1296:1337 PECM achieves good prediction performance with the ACC scores about 86% and 90% on testing and independent datasets, which are competitive with the state-of-the-art ECMs prediction tools. 25123433 0 13 theme acid 91:94 arg1 composition 96:106 Chou's pseudo amino acid composition 71:106 Chou's pseudo amino acid composition 71:106 PECM: prediction of extracellular matrix proteins using the concept of Chou's pseudo amino acid composition. 25123433 9 14 theme ECMs 1317:1320 arg1 tools 1333:1337 the state-of-the-art ECMs prediction tools 1296:1337 the state-of-the-art ECMs prediction tools 1296:1337 PECM achieves good prediction performance with the ACC scores about 86% and 90% on testing and independent datasets, which are competitive with the state-of-the-art ECMs prediction tools. 25123433 10 15 theme proposed 1385:1392 arg1 approach 1394:1401 the proposed approach 1381:1401 the proposed approach 1381:1401 A web-server named PECM which implements the proposed approach is freely available at http://59.73.198.144:8088/PECM/. 25123433 0 16 theme amino 85:89 arg1 composition 96:106 Chou's pseudo amino acid composition 71:106 Chou's pseudo amino acid composition 71:106 PECM: prediction of extracellular matrix proteins using the concept of Chou's pseudo amino acid composition. 25123433 7 17 theme feature 1060:1066 arg1 subsets 1068:1074 the optimal feature subsets 1048:1074 the optimal feature subsets 1048:1074 Rather than simply combining the features which may bring information redundancy and unwanted noises, we use Fisher-Markov selector and incremental feature selection approach to search the optimal feature subsets. 25123433 4 18 from range 527:531 arg1 targets 574:580 therapeutic targets 562:580 therapeutic targets 562:580 Accurate identification of ECMs is a significant step in understanding the evolution of cancer as well as promises wide range of potential applications in therapeutic targets or diagnostic markers. 25123433 4 18 from range 527:531 arg1 markers 596:602 diagnostic markers 585:602 diagnostic markers 585:602 Accurate identification of ECMs is a significant step in understanding the evolution of cancer as well as promises wide range of potential applications in therapeutic targets or diagnostic markers. 25123433 6 19 theme secondary 810:818 arg1 structure 820:828 predicted secondary structure 800:828 predicted secondary structure 800:828 Here, we explore various sequence-derived discriminative features including evolutionary information, predicted secondary structure, and physicochemical properties. 25123433 4 20 from targets 574:580 arg1 range 527:531 wide range 522:531 wide range of potential applications in therapeutic targets or diagnostic markers 522:602 Accurate identification of ECMs is a significant step in understanding the evolution of cancer as well as promises wide range of potential applications in therapeutic targets or diagnostic markers. 25123433 4 21 from markers 596:602 arg1 range 527:531 wide range 522:531 wide range of potential applications in therapeutic targets or diagnostic markers 522:602 Accurate identification of ECMs is a significant step in understanding the evolution of cancer as well as promises wide range of potential applications in therapeutic targets or diagnostic markers. 25123433 6 22 theme predicted 800:808 arg1 structure 820:828 predicted secondary structure 800:828 predicted secondary structure 800:828 Here, we explore various sequence-derived discriminative features including evolutionary information, predicted secondary structure, and physicochemical properties. 25123433 9 23 from datasets 1259:1266 arg1 testing 1235:1241 testing 1235:1241 testing 1235:1241 PECM achieves good prediction performance with the ACC scores about 86% and 90% on testing and independent datasets, which are competitive with the state-of-the-art ECMs prediction tools. 25123433 4 24 from applications 546:557 arg1 targets 574:580 therapeutic targets 562:580 therapeutic targets 562:580 Accurate identification of ECMs is a significant step in understanding the evolution of cancer as well as promises wide range of potential applications in therapeutic targets or diagnostic markers. 25123433 4 24 from applications 546:557 arg1 markers 596:602 diagnostic markers 585:602 diagnostic markers 585:602 Accurate identification of ECMs is a significant step in understanding the evolution of cancer as well as promises wide range of potential applications in therapeutic targets or diagnostic markers. 25123433 4 25 theme potential 536:544 arg1 applications 546:557 potential applications 536:557 potential applications in therapeutic targets or diagnostic markers 536:602 Accurate identification of ECMs is a significant step in understanding the evolution of cancer as well as promises wide range of potential applications in therapeutic targets or diagnostic markers. 25123433 5 26 theme accurate 623:630 arg1 method 646:651 an accurate computational method 620:651 an accurate computational method named PECM 620:662 In this paper, an accurate computational method named PECM is proposed for identifying ECMs. 25123433 0 27 theme proteins 41:48 arg1 prediction 6:15 prediction 6:15 PECM: prediction of extracellular matrix proteins using the concept of Chou's pseudo amino acid composition. 0:107 PECM: prediction of extracellular matrix proteins using the concept of Chou's pseudo amino acid composition. 25123433 9 28 theme prediction 1171:1180 arg1 performance 1182:1192 good prediction performance 1166:1192 good prediction performance 1166:1192 PECM achieves good prediction performance with the ACC scores about 86% and 90% on testing and independent datasets, which are competitive with the state-of-the-art ECMs prediction tools. 25123433 9 29 theme good 1166:1169 arg1 performance 1182:1192 good prediction performance 1166:1192 good prediction performance 1166:1192 PECM achieves good prediction performance with the ACC scores about 86% and 90% on testing and independent datasets, which are competitive with the state-of-the-art ECMs prediction tools. 25123433 9 30 theme ACC 1203:1205 arg1 scores 1207:1212 the ACC scores 1199:1212 the ACC scores about 86% and 90% on testing 1199:1241 PECM achieves good prediction performance with the ACC scores about 86% and 90% on testing and independent datasets, which are competitive with the state-of-the-art ECMs prediction tools. 25123433 9 30 theme ACC 1203:1205 arg1 competitive 1279:1289 competitive 1279:1289 competitive 1279:1289 PECM achieves good prediction performance with the ACC scores about 86% and 90% on testing and independent datasets, which are competitive with the state-of-the-art ECMs prediction tools. 25123433 7 31 theme incremental 999:1009 arg1 approach 1029:1036 Fisher-Markov selector and incremental feature selection approach 972:1036 approach 1029:1036 Rather than simply combining the features which may bring information redundancy and unwanted noises, we use Fisher-Markov selector and incremental feature selection approach to search the optimal feature subsets. 25123433 3 32 theme resident 362:369 arg1 cells 371:375 resident cells 362:375 resident cells 362:375 The ECMs involve the exchange of materials and information between resident cells and the external environment. 25123433 9 33 from scores 1207:1212 arg1 testing 1235:1241 testing 1235:1241 testing 1235:1241 PECM achieves good prediction performance with the ACC scores about 86% and 90% on testing and independent datasets, which are competitive with the state-of-the-art ECMs prediction tools. 25123433 0 34 theme matrix 34:39 arg1 proteins 41:48 extracellular matrix proteins 20:48 extracellular matrix proteins using the concept of Chou's pseudo amino acid composition 20:106 PECM: prediction of extracellular matrix proteins using the concept of Chou's pseudo amino acid composition. 25123433 4 35 theme applications 546:557 arg1 range 527:531 wide range 522:531 wide range of potential applications in therapeutic targets or diagnostic markers 522:602 Accurate identification of ECMs is a significant step in understanding the evolution of cancer as well as promises wide range of potential applications in therapeutic targets or diagnostic markers. 25123433 8 36 theme support 1122:1128 arg1 machine 1137:1143 support vector machine 1122:1143 support vector machine (SVM) 1122:1149 Then, we train our model by the technique of support vector machine (SVM). 25123433 8 36 theme support 1122:1128 arg1 SVM 1146:1148 SVM 1146:1148 SVM 1146:1148 Then, we train our model by the technique of support vector machine (SVM). 25123433 0 37 theme extracellular 20:32 arg1 proteins 41:48 extracellular matrix proteins 20:48 extracellular matrix proteins using the concept of Chou's pseudo amino acid composition 20:106 PECM: prediction of extracellular matrix proteins using the concept of Chou's pseudo amino acid composition. 25123433 1 38 located found 161:165 arg2 ECMs 144:147 ECMs 144:147 ECMs 144:147 The extracellular matrix proteins (ECMs) are widely found in the tissues of multicellular organisms. 25123433 1 38 located found 161:165 arg2 proteins 134:141 The extracellular matrix proteins 109:141 The extracellular matrix proteins (ECMs) 109:148 The extracellular matrix proteins (ECMs) are widely found in the tissues of multicellular organisms. 25123433 1 38 located found 161:165 arg1 tissues 174:180 the tissues 170:180 the tissues of multicellular organisms 170:207 The extracellular matrix proteins (ECMs) are widely found in the tissues of multicellular organisms. 25123433 6 39 theme evolutionary 774:785 arg1 information 787:797 evolutionary information 774:797 evolutionary information 774:797 Here, we explore various sequence-derived discriminative features including evolutionary information, predicted secondary structure, and physicochemical properties. 25123433 3 40 theme materials 328:336 arg1 exchange 316:323 the exchange 312:323 the exchange of materials and information between resident cells and the external environment 312:404 The ECMs involve the exchange of materials and information between resident cells and the external environment. 25123433 6 41 link sequence-derived 723:738 arg1 features 755:762 various sequence-derived discriminative features 715:762 various sequence-derived discriminative features including evolutionary information, predicted secondary structure, and physicochemical properties 715:860 Here, we explore various sequence-derived discriminative features including evolutionary information, predicted secondary structure, and physicochemical properties. 25123433 6 41 link sequence-derived 723:738 arg1 properties 851:860 physicochemical properties 835:860 physicochemical properties 835:860 Here, we explore various sequence-derived discriminative features including evolutionary information, predicted secondary structure, and physicochemical properties. 25123433 6 41 link sequence-derived 723:738 arg1 information 787:797 evolutionary information 774:797 evolutionary information 774:797 Here, we explore various sequence-derived discriminative features including evolutionary information, predicted secondary structure, and physicochemical properties. 25123433 6 41 link sequence-derived 723:738 arg1 structure 820:828 predicted secondary structure 800:828 predicted secondary structure 800:828 Here, we explore various sequence-derived discriminative features including evolutionary information, predicted secondary structure, and physicochemical properties. 25123433 8 42 theme machine 1137:1143 arg1 technique 1109:1117 the technique 1105:1117 the technique of support vector machine (SVM) 1105:1149 Then, we train our model by the technique of support vector machine (SVM). 25123433 4 43 theme significant 444:454 arg1 identification 416:429 Accurate identification 407:429 Accurate identification of ECMs 407:437 Accurate identification of ECMs is a significant step in understanding the evolution of cancer as well as promises wide range of potential applications in therapeutic targets or diagnostic markers. 25123433 4 43 theme significant 444:454 arg1 step 456:459 a significant step 442:459 a significant step in understanding the evolution of cancer as well as promises wide range of potential applications in therapeutic targets or diagnostic markers 442:602 Accurate identification of ECMs is a significant step in understanding the evolution of cancer as well as promises wide range of potential applications in therapeutic targets or diagnostic markers. 25123433 9 44 theme prediction 1322:1331 arg1 tools 1333:1337 the state-of-the-art ECMs prediction tools 1296:1337 the state-of-the-art ECMs prediction tools 1296:1337 PECM achieves good prediction performance with the ACC scores about 86% and 90% on testing and independent datasets, which are competitive with the state-of-the-art ECMs prediction tools. 25123433 3 45 theme external 385:392 arg1 environment 394:404 the external environment 381:404 the external environment 381:404 The ECMs involve the exchange of materials and information between resident cells and the external environment. 25123433 8 46 theme vector 1130:1135 arg1 machine 1137:1143 support vector machine 1122:1143 support vector machine (SVM) 1122:1149 Then, we train our model by the technique of support vector machine (SVM). 25123433 8 46 theme vector 1130:1135 arg1 SVM 1146:1148 SVM 1146:1148 SVM 1146:1148 Then, we train our model by the technique of support vector machine (SVM). 25123433 9 47 theme independent 1247:1257 arg1 datasets 1259:1266 independent datasets 1247:1266 independent datasets 1247:1266 PECM achieves good prediction performance with the ACC scores about 86% and 90% on testing and independent datasets, which are competitive with the state-of-the-art ECMs prediction tools. 25123433 7 48 theme unwanted 948:955 arg1 noises 957:962 unwanted noises 948:962 unwanted noises 948:962 Rather than simply combining the features which may bring information redundancy and unwanted noises, we use Fisher-Markov selector and incremental feature selection approach to search the optimal feature subsets. 25123433 4 49 theme wide 522:525 arg1 range 527:531 wide range 522:531 wide range of potential applications in therapeutic targets or diagnostic markers 522:602 Accurate identification of ECMs is a significant step in understanding the evolution of cancer as well as promises wide range of potential applications in therapeutic targets or diagnostic markers. 25123433 4 50 theme Accurate 407:414 arg1 identification 416:429 Accurate identification 407:429 Accurate identification of ECMs 407:437 Accurate identification of ECMs is a significant step in understanding the evolution of cancer as well as promises wide range of potential applications in therapeutic targets or diagnostic markers. 25123433 4 50 theme Accurate 407:414 arg1 step 456:459 a significant step 442:459 a significant step in understanding the evolution of cancer as well as promises wide range of potential applications in therapeutic targets or diagnostic markers 442:602 Accurate identification of ECMs is a significant step in understanding the evolution of cancer as well as promises wide range of potential applications in therapeutic targets or diagnostic markers. 25123433 2 51 theme secreted 234:241 arg1 proteins 243:250 various secreted proteins 226:250 various secreted proteins 226:250 They consist of various secreted proteins, mainly polysaccharides and glycoproteins. 25123433 6 52 theme discriminative 740:753 arg1 features 755:762 various sequence-derived discriminative features 715:762 various sequence-derived discriminative features including evolutionary information, predicted secondary structure, and physicochemical properties 715:860 Here, we explore various sequence-derived discriminative features including evolutionary information, predicted secondary structure, and physicochemical properties. 25123433 6 52 theme discriminative 740:753 arg1 properties 851:860 physicochemical properties 835:860 physicochemical properties 835:860 Here, we explore various sequence-derived discriminative features including evolutionary information, predicted secondary structure, and physicochemical properties. 25123433 6 52 theme discriminative 740:753 arg1 information 787:797 evolutionary information 774:797 evolutionary information 774:797 Here, we explore various sequence-derived discriminative features including evolutionary information, predicted secondary structure, and physicochemical properties. 25123433 6 52 theme discriminative 740:753 arg1 structure 820:828 predicted secondary structure 800:828 predicted secondary structure 800:828 Here, we explore various sequence-derived discriminative features including evolutionary information, predicted secondary structure, and physicochemical properties. 25123433 7 53 dep Rather 863:868 arg1 combining 882:890 combining 882:890 combining the features which may bring information redundancy and unwanted noises 882:962 Rather than simply combining the features which may bring information redundancy and unwanted noises, we use Fisher-Markov selector and incremental feature selection approach to search the optimal feature subsets. 25123433 1 54 theme multicellular 185:197 arg1 organisms 199:207 multicellular organisms 185:207 multicellular organisms 185:207 The extracellular matrix proteins (ECMs) are widely found in the tissues of multicellular organisms. 25123433 7 55 theme optimal 1052:1058 arg1 subsets 1068:1074 the optimal feature subsets 1048:1074 the optimal feature subsets 1048:1074 Rather than simply combining the features which may bring information redundancy and unwanted noises, we use Fisher-Markov selector and incremental feature selection approach to search the optimal feature subsets. 25123433 4 56 theme ECMs 434:437 arg1 identification 416:429 Accurate identification 407:429 Accurate identification of ECMs 407:437 Accurate identification of ECMs is a significant step in understanding the evolution of cancer as well as promises wide range of potential applications in therapeutic targets or diagnostic markers. 25123433 4 56 theme ECMs 434:437 arg1 step 456:459 a significant step 442:459 a significant step in understanding the evolution of cancer as well as promises wide range of potential applications in therapeutic targets or diagnostic markers 442:602 Accurate identification of ECMs is a significant step in understanding the evolution of cancer as well as promises wide range of potential applications in therapeutic targets or diagnostic markers. 25123433 2 57 theme various 226:232 arg1 proteins 243:250 various secreted proteins 226:250 various secreted proteins 226:250 They consist of various secreted proteins, mainly polysaccharides and glycoproteins. 25123433 6 58 theme sequence-derived 723:738 arg1 features 755:762 various sequence-derived discriminative features 715:762 various sequence-derived discriminative features including evolutionary information, predicted secondary structure, and physicochemical properties 715:860 Here, we explore various sequence-derived discriminative features including evolutionary information, predicted secondary structure, and physicochemical properties. 25123433 6 58 theme sequence-derived 723:738 arg1 properties 851:860 physicochemical properties 835:860 physicochemical properties 835:860 Here, we explore various sequence-derived discriminative features including evolutionary information, predicted secondary structure, and physicochemical properties. 25123433 6 58 theme sequence-derived 723:738 arg1 information 787:797 evolutionary information 774:797 evolutionary information 774:797 Here, we explore various sequence-derived discriminative features including evolutionary information, predicted secondary structure, and physicochemical properties. 25123433 6 58 theme sequence-derived 723:738 arg1 structure 820:828 predicted secondary structure 800:828 predicted secondary structure 800:828 Here, we explore various sequence-derived discriminative features including evolutionary information, predicted secondary structure, and physicochemical properties. 25123433 1 59 theme extracellular 113:125 arg1 proteins 134:141 The extracellular matrix proteins 109:141 The extracellular matrix proteins (ECMs) 109:148 The extracellular matrix proteins (ECMs) are widely found in the tissues of multicellular organisms. 25123433 1 59 theme extracellular 113:125 arg1 ECMs 144:147 ECMs 144:147 ECMs 144:147 The extracellular matrix proteins (ECMs) are widely found in the tissues of multicellular organisms. 25123433 10 60 theme named 1353:1357 arg1 available 1413:1421 available 1413:1421 available 1413:1421 A web-server named PECM which implements the proposed approach is freely available at http://59.73.198.144:8088/PECM/. 25123433 10 60 theme named 1353:1357 arg1 PECM 1359:1362 A web-server named PECM 1340:1362 A web-server named PECM which implements the proposed approach 1340:1401 A web-server named PECM which implements the proposed approach is freely available at http://59.73.198.144:8088/PECM/. 25123433 1 61 theme organisms 199:207 arg1 tissues 174:180 the tissues 170:180 the tissues of multicellular organisms 170:207 The extracellular matrix proteins (ECMs) are widely found in the tissues of multicellular organisms. 25123433 6 62 theme various 715:721 arg1 features 755:762 various sequence-derived discriminative features 715:762 various sequence-derived discriminative features including evolutionary information, predicted secondary structure, and physicochemical properties 715:860 Here, we explore various sequence-derived discriminative features including evolutionary information, predicted secondary structure, and physicochemical properties. 25123433 6 62 theme various 715:721 arg1 properties 851:860 physicochemical properties 835:860 physicochemical properties 835:860 Here, we explore various sequence-derived discriminative features including evolutionary information, predicted secondary structure, and physicochemical properties. 25123433 6 62 theme various 715:721 arg1 information 787:797 evolutionary information 774:797 evolutionary information 774:797 Here, we explore various sequence-derived discriminative features including evolutionary information, predicted secondary structure, and physicochemical properties. 25123433 6 62 theme various 715:721 arg1 structure 820:828 predicted secondary structure 800:828 predicted secondary structure 800:828 Here, we explore various sequence-derived discriminative features including evolutionary information, predicted secondary structure, and physicochemical properties. 25123433 1 63 theme matrix 127:132 arg1 proteins 134:141 The extracellular matrix proteins 109:141 The extracellular matrix proteins (ECMs) 109:148 The extracellular matrix proteins (ECMs) are widely found in the tissues of multicellular organisms. 25123433 1 63 theme matrix 127:132 arg1 ECMs 144:147 ECMs 144:147 ECMs 144:147 The extracellular matrix proteins (ECMs) are widely found in the tissues of multicellular organisms. 25123433 4 64 theme cancer 495:500 arg1 evolution 482:490 the evolution 478:490 the evolution of cancer 478:500 Accurate identification of ECMs is a significant step in understanding the evolution of cancer as well as promises wide range of potential applications in therapeutic targets or diagnostic markers. 25123433 0 65 dep PECM 0:3 arg1 prediction 6:15 prediction 6:15 PECM: prediction of extracellular matrix proteins using the concept of Chou's pseudo amino acid composition. 0:107 PECM: prediction of extracellular matrix proteins using the concept of Chou's pseudo amino acid composition. 25123433 7 66 theme selection 1019:1027 arg1 approach 1029:1036 Fisher-Markov selector and incremental feature selection approach 972:1036 approach 1029:1036 Rather than simply combining the features which may bring information redundancy and unwanted noises, we use Fisher-Markov selector and incremental feature selection approach to search the optimal feature subsets. 24575887 6 0 theme surface 1276:1282 arg1 section 1284:1290 the surface section 1272:1290 the surface section 1272:1290 Cell viability in biofilms was also spatially influenced by monochloramine diffusion and reaction within biofilms, showing a lower survival in the surface section and a higher persistence in the middle section of the P. putida biofilm compared to the P. aeruginosa biofilms. 24575887 6 1 from persistence 1305:1315 arg1 section 1284:1290 the surface section 1272:1290 the surface section 1272:1290 Cell viability in biofilms was also spatially influenced by monochloramine diffusion and reaction within biofilms, showing a lower survival in the surface section and a higher persistence in the middle section of the P. putida biofilm compared to the P. aeruginosa biofilms. 24575887 6 1 from persistence 1305:1315 arg1 section 1331:1337 the middle section 1320:1337 the middle section of the P. putida biofilm compared to the P. aeruginosa biofilms 1320:1401 Cell viability in biofilms was also spatially influenced by monochloramine diffusion and reaction within biofilms, showing a lower survival in the surface section and a higher persistence in the middle section of the P. putida biofilm compared to the P. aeruginosa biofilms. 24575887 7 2 theme protein 1526:1532 arg1 EPS 1534:1536 protein EPS 1526:1536 protein EPS 1526:1536 While polysaccharide EPS promoted biofilm cell viability by obstructing monochloramine reactive sites on bacterial cells, protein EPS hindered monochloramine penetration by reacting with monochloramine and reduced its concentration within biofilms. 24575887 7 3 theme monochloramine 1476:1489 arg1 sites 1500:1504 monochloramine reactive sites 1476:1504 monochloramine reactive sites on bacterial cells 1476:1523 While polysaccharide EPS promoted biofilm cell viability by obstructing monochloramine reactive sites on bacterial cells, protein EPS hindered monochloramine penetration by reacting with monochloramine and reduced its concentration within biofilms. 24575887 3 4 theme detached 733:740 arg1 clusters 742:749 detached clusters 733:749 detached clusters 733:749 The different reactivity of EPS components with monochloramine influenced disinfectant penetration, biofilm inactivation, as well as the viability of detached clusters. 24575887 6 5 dep P. 1346:1347 arg1 putida 1349:1354 putida 1349:1354 putida 1349:1354 Cell viability in biofilms was also spatially influenced by monochloramine diffusion and reaction within biofilms, showing a lower survival in the surface section and a higher persistence in the middle section of the P. putida biofilm compared to the P. aeruginosa biofilms. 24575887 7 6 theme cell 1446:1449 arg1 viability 1451:1459 biofilm cell viability 1438:1459 biofilm cell viability 1438:1459 While polysaccharide EPS promoted biofilm cell viability by obstructing monochloramine reactive sites on bacterial cells, protein EPS hindered monochloramine penetration by reacting with monochloramine and reduced its concentration within biofilms. 24575887 5 7 dep time 1048:1051 arg1 the 1044:1046 the 1044:1046 the 1044:1046 The reaction with proteins in P. putida EPS multiplied both the time and the monochloramine mass required to achieve a full biofilm penetration. 24575887 5 8 theme biofilm 1108:1114 arg1 penetration 1116:1126 a full biofilm penetration 1101:1126 a full biofilm penetration 1101:1126 The reaction with proteins in P. putida EPS multiplied both the time and the monochloramine mass required to achieve a full biofilm penetration. 24575887 3 9 theme EPS 611:613 arg1 components 615:624 EPS components 611:624 EPS components 611:624 The different reactivity of EPS components with monochloramine influenced disinfectant penetration, biofilm inactivation, as well as the viability of detached clusters. 24575887 8 10 theme monochloramine 1837:1850 arg1 levels 1861:1866 currently recommended monochloramine residual levels 1815:1866 currently recommended monochloramine residual levels 1815:1866 Furthermore, the persistence of bacterial cells detached from biofilm (over 70% for P. putida and ∼40% for polysaccharide producing P. aeruginosa) suggested that currently recommended monochloramine residual levels may underestimate the risk of water quality deterioration caused by biofilm detachment. 24575887 1 11 theme polymeric 244:252 arg1 EPS 266:268 EPS 266:268 EPS 266:268 The efficiency of monochloramine disinfection was dependent on the quantity and composition of extracellular polymeric substances (EPS) in biofilms, as monochloramine has a selective reactivity with proteins over polysaccharides. 24575887 1 11 theme polymeric 244:252 arg1 substances 254:263 extracellular polymeric substances 230:263 extracellular polymeric substances (EPS) 230:269 The efficiency of monochloramine disinfection was dependent on the quantity and composition of extracellular polymeric substances (EPS) in biofilms, as monochloramine has a selective reactivity with proteins over polysaccharides. 24575887 7 12 theme polysaccharide 1410:1423 arg1 EPS 1425:1427 polysaccharide EPS 1410:1427 polysaccharide EPS 1410:1427 While polysaccharide EPS promoted biofilm cell viability by obstructing monochloramine reactive sites on bacterial cells, protein EPS hindered monochloramine penetration by reacting with monochloramine and reduced its concentration within biofilms. 24575887 1 13 from composition 215:225 arg1 biofilms 274:281 biofilms 274:281 biofilms 274:281 The efficiency of monochloramine disinfection was dependent on the quantity and composition of extracellular polymeric substances (EPS) in biofilms, as monochloramine has a selective reactivity with proteins over polysaccharides. 24575887 4 14 theme Monochloramine 752:765 arg1 profiling 777:785 Monochloramine transport profiling 752:785 Monochloramine transport profiling measured by a chloramine-sensitive microelectrode 752:835 Monochloramine transport profiling measured by a chloramine-sensitive microelectrode revealed a broader diffusion boundary layer between bulk and biofilm surface in the P. putida biofilm compared to those of P. aeruginosa biofilms. 24575887 2 15 with biofilms 480:487 arg1 amount 501:506 varied amount 494:506 varied amount of polysaccharide EPS (wild-type and mutant P. aeruginosa) 494:565 Biofilms with protein-based (Pseudomonas putida) and polysaccharide based EPS (Pseudomonas aeruginosa), as well as biofilms with varied amount of polysaccharide EPS (wild-type and mutant P. aeruginosa), were compared. 24575887 2 15 with biofilms 480:487 arg1 EPS 526:528 polysaccharide EPS 511:528 polysaccharide EPS (wild-type and mutant P. aeruginosa) 511:565 Biofilms with protein-based (Pseudomonas putida) and polysaccharide based EPS (Pseudomonas aeruginosa), as well as biofilms with varied amount of polysaccharide EPS (wild-type and mutant P. aeruginosa), were compared. 24575887 2 16 theme EPS 526:528 arg1 amount 501:506 varied amount 494:506 varied amount of polysaccharide EPS (wild-type and mutant P. aeruginosa) 494:565 Biofilms with protein-based (Pseudomonas putida) and polysaccharide based EPS (Pseudomonas aeruginosa), as well as biofilms with varied amount of polysaccharide EPS (wild-type and mutant P. aeruginosa), were compared. 24575887 2 16 theme EPS 526:528 arg1 EPS 526:528 polysaccharide EPS 511:528 polysaccharide EPS (wild-type and mutant P. aeruginosa) 511:565 Biofilms with protein-based (Pseudomonas putida) and polysaccharide based EPS (Pseudomonas aeruginosa), as well as biofilms with varied amount of polysaccharide EPS (wild-type and mutant P. aeruginosa), were compared. 24575887 6 17 theme lower 1254:1258 arg1 survival 1260:1267 a lower survival 1252:1267 a lower survival in the surface section 1252:1290 Cell viability in biofilms was also spatially influenced by monochloramine diffusion and reaction within biofilms, showing a lower survival in the surface section and a higher persistence in the middle section of the P. putida biofilm compared to the P. aeruginosa biofilms. 24575887 1 18 theme disinfection 168:179 arg1 efficiency 139:148 The efficiency 135:148 The efficiency of monochloramine disinfection 135:179 The efficiency of monochloramine disinfection was dependent on the quantity and composition of extracellular polymeric substances (EPS) in biofilms, as monochloramine has a selective reactivity with proteins over polysaccharides. 24575887 1 18 theme disinfection 168:179 arg1 dependent 185:193 dependent 185:193 dependent 185:193 The efficiency of monochloramine disinfection was dependent on the quantity and composition of extracellular polymeric substances (EPS) in biofilms, as monochloramine has a selective reactivity with proteins over polysaccharides. 24575887 8 19 theme water 1898:1902 arg1 deterioration 1912:1924 water quality deterioration 1898:1924 water quality deterioration 1898:1924 Furthermore, the persistence of bacterial cells detached from biofilm (over 70% for P. putida and ∼40% for polysaccharide producing P. aeruginosa) suggested that currently recommended monochloramine residual levels may underestimate the risk of water quality deterioration caused by biofilm detachment. 24575887 7 20 from sites 1500:1504 arg1 cells 1519:1523 bacterial cells 1509:1523 bacterial cells 1509:1523 While polysaccharide EPS promoted biofilm cell viability by obstructing monochloramine reactive sites on bacterial cells, protein EPS hindered monochloramine penetration by reacting with monochloramine and reduced its concentration within biofilms. 24575887 4 21 theme chloramine-sensitive 801:820 arg1 microelectrode 822:835 a chloramine-sensitive microelectrode 799:835 a chloramine-sensitive microelectrode 799:835 Monochloramine transport profiling measured by a chloramine-sensitive microelectrode revealed a broader diffusion boundary layer between bulk and biofilm surface in the P. putida biofilm compared to those of P. aeruginosa biofilms. 24575887 6 22 from survival 1260:1267 arg1 section 1284:1290 the surface section 1272:1290 the surface section 1272:1290 Cell viability in biofilms was also spatially influenced by monochloramine diffusion and reaction within biofilms, showing a lower survival in the surface section and a higher persistence in the middle section of the P. putida biofilm compared to the P. aeruginosa biofilms. 24575887 6 22 from survival 1260:1267 arg1 section 1331:1337 the middle section 1320:1337 the middle section of the P. putida biofilm compared to the P. aeruginosa biofilms 1320:1401 Cell viability in biofilms was also spatially influenced by monochloramine diffusion and reaction within biofilms, showing a lower survival in the surface section and a higher persistence in the middle section of the P. putida biofilm compared to the P. aeruginosa biofilms. 24575887 0 23 theme biofilm 104:110 arg1 disinfection 88:99 the disinfection 84:99 the disinfection of biofilm and detached clusters 84:132 Selective reactivity of monochloramine with extracellular matrix components affects the disinfection of biofilm and detached clusters. 24575887 8 24 theme deterioration 1912:1924 arg1 risk 1890:1893 the risk 1886:1893 the risk of water quality deterioration caused by biofilm detachment 1886:1953 Furthermore, the persistence of bacterial cells detached from biofilm (over 70% for P. putida and ∼40% for polysaccharide producing P. aeruginosa) suggested that currently recommended monochloramine residual levels may underestimate the risk of water quality deterioration caused by biofilm detachment. 24575887 2 25 theme based 433:437 arg1 EPS 439:441 protein-based (Pseudomonas putida) and polysaccharide based EPS 379:441 EPS 439:441 Biofilms with protein-based (Pseudomonas putida) and polysaccharide based EPS (Pseudomonas aeruginosa), as well as biofilms with varied amount of polysaccharide EPS (wild-type and mutant P. aeruginosa), were compared. 24575887 0 26 theme detached 116:123 arg1 clusters 125:132 detached clusters 116:132 detached clusters 116:132 Selective reactivity of monochloramine with extracellular matrix components affects the disinfection of biofilm and detached clusters. 24575887 0 27 theme Selective 0:8 arg1 reactivity 10:19 Selective reactivity 0:19 Selective reactivity of monochloramine with extracellular matrix components 0:74 Selective reactivity of monochloramine with extracellular matrix components affects the disinfection of biofilm and detached clusters. 24575887 2 28 theme varied 494:499 arg1 amount 501:506 varied amount 494:506 varied amount of polysaccharide EPS (wild-type and mutant P. aeruginosa) 494:565 Biofilms with protein-based (Pseudomonas putida) and polysaccharide based EPS (Pseudomonas aeruginosa), as well as biofilms with varied amount of polysaccharide EPS (wild-type and mutant P. aeruginosa), were compared. 24575887 2 28 theme varied 494:499 arg1 EPS 526:528 polysaccharide EPS 511:528 polysaccharide EPS (wild-type and mutant P. aeruginosa) 511:565 Biofilms with protein-based (Pseudomonas putida) and polysaccharide based EPS (Pseudomonas aeruginosa), as well as biofilms with varied amount of polysaccharide EPS (wild-type and mutant P. aeruginosa), were compared. 24575887 3 29 theme biofilm 683:689 arg1 inactivation 691:702 biofilm inactivation 683:702 biofilm inactivation 683:702 The different reactivity of EPS components with monochloramine influenced disinfectant penetration, biofilm inactivation, as well as the viability of detached clusters. 24575887 1 30 dep quantity 202:209 arg1 the 198:200 the 198:200 the 198:200 The efficiency of monochloramine disinfection was dependent on the quantity and composition of extracellular polymeric substances (EPS) in biofilms, as monochloramine has a selective reactivity with proteins over polysaccharides. 24575887 5 31 theme monochloramine 1061:1074 arg1 mass 1076:1079 the monochloramine mass 1057:1079 the monochloramine mass 1057:1079 The reaction with proteins in P. putida EPS multiplied both the time and the monochloramine mass required to achieve a full biofilm penetration. 24575887 0 32 theme matrix 58:63 arg1 components 65:74 extracellular matrix components 44:74 extracellular matrix components 44:74 Selective reactivity of monochloramine with extracellular matrix components affects the disinfection of biofilm and detached clusters. 24575887 4 33 theme broader 848:854 arg1 layer 875:879 a broader diffusion boundary layer 846:879 a broader diffusion boundary layer between bulk and biofilm surface 846:912 Monochloramine transport profiling measured by a chloramine-sensitive microelectrode revealed a broader diffusion boundary layer between bulk and biofilm surface in the P. putida biofilm compared to those of P. aeruginosa biofilms. 24575887 1 34 theme substances 254:263 arg1 quantity 202:209 quantity 202:209 quantity 202:209 The efficiency of monochloramine disinfection was dependent on the quantity and composition of extracellular polymeric substances (EPS) in biofilms, as monochloramine has a selective reactivity with proteins over polysaccharides. 24575887 1 34 theme substances 254:263 arg1 composition 215:225 composition 215:225 composition 215:225 The efficiency of monochloramine disinfection was dependent on the quantity and composition of extracellular polymeric substances (EPS) in biofilms, as monochloramine has a selective reactivity with proteins over polysaccharides. 24575887 8 35 theme bacterial 1685:1693 arg1 cells 1695:1699 bacterial cells 1685:1699 bacterial cells detached from biofilm (over 70% for P. putida and ∼40% for polysaccharide producing P. aeruginosa) 1685:1798 Furthermore, the persistence of bacterial cells detached from biofilm (over 70% for P. putida and ∼40% for polysaccharide producing P. aeruginosa) suggested that currently recommended monochloramine residual levels may underestimate the risk of water quality deterioration caused by biofilm detachment. 24575887 4 36 theme boundary 866:873 arg1 layer 875:879 a broader diffusion boundary layer 846:879 a broader diffusion boundary layer between bulk and biofilm surface 846:912 Monochloramine transport profiling measured by a chloramine-sensitive microelectrode revealed a broader diffusion boundary layer between bulk and biofilm surface in the P. putida biofilm compared to those of P. aeruginosa biofilms. 24575887 6 37 from viability 1134:1142 arg1 biofilms 1147:1154 biofilms 1147:1154 biofilms 1147:1154 Cell viability in biofilms was also spatially influenced by monochloramine diffusion and reaction within biofilms, showing a lower survival in the surface section and a higher persistence in the middle section of the P. putida biofilm compared to the P. aeruginosa biofilms. 24575887 7 38 theme monochloramine 1547:1560 arg1 penetration 1562:1572 monochloramine penetration 1547:1572 monochloramine penetration 1547:1572 While polysaccharide EPS promoted biofilm cell viability by obstructing monochloramine reactive sites on bacterial cells, protein EPS hindered monochloramine penetration by reacting with monochloramine and reduced its concentration within biofilms. 24575887 4 39 theme P. 921:922 arg1 biofilm 931:937 the P. putida biofilm 917:937 the P. putida biofilm 917:937 Monochloramine transport profiling measured by a chloramine-sensitive microelectrode revealed a broader diffusion boundary layer between bulk and biofilm surface in the P. putida biofilm compared to those of P. aeruginosa biofilms. 24575887 6 40 theme middle 1324:1329 arg1 section 1331:1337 the middle section 1320:1337 the middle section of the P. putida biofilm compared to the P. aeruginosa biofilms 1320:1401 Cell viability in biofilms was also spatially influenced by monochloramine diffusion and reaction within biofilms, showing a lower survival in the surface section and a higher persistence in the middle section of the P. putida biofilm compared to the P. aeruginosa biofilms. 24575887 1 41 with reactivity 318:327 arg1 proteins 334:341 proteins 334:341 proteins 334:341 The efficiency of monochloramine disinfection was dependent on the quantity and composition of extracellular polymeric substances (EPS) in biofilms, as monochloramine has a selective reactivity with proteins over polysaccharides. 24575887 1 42 contain has 302:304 arg1 monochloramine 287:300 monochloramine 287:300 monochloramine 287:300 The efficiency of monochloramine disinfection was dependent on the quantity and composition of extracellular polymeric substances (EPS) in biofilms, as monochloramine has a selective reactivity with proteins over polysaccharides. 24575887 1 42 contain has 302:304 arg2 reactivity 318:327 a selective reactivity 306:327 a selective reactivity with proteins 306:341 The efficiency of monochloramine disinfection was dependent on the quantity and composition of extracellular polymeric substances (EPS) in biofilms, as monochloramine has a selective reactivity with proteins over polysaccharides. 24575887 7 43 theme bacterial 1509:1517 arg1 cells 1519:1523 bacterial cells 1509:1523 bacterial cells 1509:1523 While polysaccharide EPS promoted biofilm cell viability by obstructing monochloramine reactive sites on bacterial cells, protein EPS hindered monochloramine penetration by reacting with monochloramine and reduced its concentration within biofilms. 24575887 4 44 theme biofilm 898:904 arg1 surface 906:912 bulk and biofilm surface 889:912 surface 906:912 Monochloramine transport profiling measured by a chloramine-sensitive microelectrode revealed a broader diffusion boundary layer between bulk and biofilm surface in the P. putida biofilm compared to those of P. aeruginosa biofilms. 24575887 7 45 theme reactive 1491:1498 arg1 sites 1500:1504 monochloramine reactive sites 1476:1504 monochloramine reactive sites on bacterial cells 1476:1523 While polysaccharide EPS promoted biofilm cell viability by obstructing monochloramine reactive sites on bacterial cells, protein EPS hindered monochloramine penetration by reacting with monochloramine and reduced its concentration within biofilms. 24575887 3 46 theme clusters 742:749 arg1 viability 720:728 the viability 716:728 the viability of detached clusters 716:749 The different reactivity of EPS components with monochloramine influenced disinfectant penetration, biofilm inactivation, as well as the viability of detached clusters. 24575887 3 46 theme clusters 742:749 arg1 penetration 670:680 disinfectant penetration 657:680 disinfectant penetration 657:680 The different reactivity of EPS components with monochloramine influenced disinfectant penetration, biofilm inactivation, as well as the viability of detached clusters. 24575887 3 46 theme clusters 742:749 arg1 inactivation 691:702 biofilm inactivation 683:702 biofilm inactivation 683:702 The different reactivity of EPS components with monochloramine influenced disinfectant penetration, biofilm inactivation, as well as the viability of detached clusters. 24575887 6 47 theme higher 1298:1303 arg1 persistence 1305:1315 a higher persistence 1296:1315 a higher persistence in the middle section of the P. putida biofilm compared to the P. aeruginosa biofilms 1296:1401 Cell viability in biofilms was also spatially influenced by monochloramine diffusion and reaction within biofilms, showing a lower survival in the surface section and a higher persistence in the middle section of the P. putida biofilm compared to the P. aeruginosa biofilms. 24575887 5 48 with reaction 988:995 arg1 proteins 1002:1009 proteins 1002:1009 proteins 1002:1009 The reaction with proteins in P. putida EPS multiplied both the time and the monochloramine mass required to achieve a full biofilm penetration. 24575887 4 49 theme aeruginosa 963:972 arg1 biofilms 974:981 P. aeruginosa biofilms 960:981 P. aeruginosa biofilms 960:981 Monochloramine transport profiling measured by a chloramine-sensitive microelectrode revealed a broader diffusion boundary layer between bulk and biofilm surface in the P. putida biofilm compared to those of P. aeruginosa biofilms. 24575887 6 50 theme monochloramine 1189:1202 arg1 diffusion 1204:1212 monochloramine diffusion 1189:1212 monochloramine diffusion 1189:1212 Cell viability in biofilms was also spatially influenced by monochloramine diffusion and reaction within biofilms, showing a lower survival in the surface section and a higher persistence in the middle section of the P. putida biofilm compared to the P. aeruginosa biofilms. 24575887 1 51 theme extracellular 230:242 arg1 EPS 266:268 EPS 266:268 EPS 266:268 The efficiency of monochloramine disinfection was dependent on the quantity and composition of extracellular polymeric substances (EPS) in biofilms, as monochloramine has a selective reactivity with proteins over polysaccharides. 24575887 1 51 theme extracellular 230:242 arg1 substances 254:263 extracellular polymeric substances 230:263 extracellular polymeric substances (EPS) 230:269 The efficiency of monochloramine disinfection was dependent on the quantity and composition of extracellular polymeric substances (EPS) in biofilms, as monochloramine has a selective reactivity with proteins over polysaccharides. 24575887 7 52 theme biofilm 1438:1444 arg1 viability 1451:1459 biofilm cell viability 1438:1459 biofilm cell viability 1438:1459 While polysaccharide EPS promoted biofilm cell viability by obstructing monochloramine reactive sites on bacterial cells, protein EPS hindered monochloramine penetration by reacting with monochloramine and reduced its concentration within biofilms. 24575887 6 53 theme biofilm 1356:1362 arg1 section 1331:1337 the middle section 1320:1337 the middle section of the P. putida biofilm compared to the P. aeruginosa biofilms 1320:1401 Cell viability in biofilms was also spatially influenced by monochloramine diffusion and reaction within biofilms, showing a lower survival in the surface section and a higher persistence in the middle section of the P. putida biofilm compared to the P. aeruginosa biofilms. 24575887 3 54 theme different 587:595 arg1 reactivity 597:606 The different reactivity 583:606 The different reactivity of EPS components with monochloramine 583:644 The different reactivity of EPS components with monochloramine influenced disinfectant penetration, biofilm inactivation, as well as the viability of detached clusters. 24575887 8 55 theme recommended 1825:1835 arg1 levels 1861:1866 currently recommended monochloramine residual levels 1815:1866 currently recommended monochloramine residual levels 1815:1866 Furthermore, the persistence of bacterial cells detached from biofilm (over 70% for P. putida and ∼40% for polysaccharide producing P. aeruginosa) suggested that currently recommended monochloramine residual levels may underestimate the risk of water quality deterioration caused by biofilm detachment. 24575887 6 56 theme P. 1346:1347 arg1 biofilm 1356:1362 the P. putida biofilm 1342:1362 the P. putida biofilm compared to the P. aeruginosa biofilms 1342:1401 Cell viability in biofilms was also spatially influenced by monochloramine diffusion and reaction within biofilms, showing a lower survival in the surface section and a higher persistence in the middle section of the P. putida biofilm compared to the P. aeruginosa biofilms. 24575887 8 57 theme residual 1852:1859 arg1 levels 1861:1866 currently recommended monochloramine residual levels 1815:1866 currently recommended monochloramine residual levels 1815:1866 Furthermore, the persistence of bacterial cells detached from biofilm (over 70% for P. putida and ∼40% for polysaccharide producing P. aeruginosa) suggested that currently recommended monochloramine residual levels may underestimate the risk of water quality deterioration caused by biofilm detachment. 24575887 5 58 theme full 1103:1106 arg1 penetration 1116:1126 a full biofilm penetration 1101:1126 a full biofilm penetration 1101:1126 The reaction with proteins in P. putida EPS multiplied both the time and the monochloramine mass required to achieve a full biofilm penetration. 24575887 3 59 theme components 615:624 arg1 reactivity 597:606 The different reactivity 583:606 The different reactivity of EPS components with monochloramine 583:644 The different reactivity of EPS components with monochloramine influenced disinfectant penetration, biofilm inactivation, as well as the viability of detached clusters. 24575887 1 60 theme monochloramine 153:166 arg1 disinfection 168:179 monochloramine disinfection 153:179 monochloramine disinfection 153:179 The efficiency of monochloramine disinfection was dependent on the quantity and composition of extracellular polymeric substances (EPS) in biofilms, as monochloramine has a selective reactivity with proteins over polysaccharides. 24575887 2 61 theme polysaccharide 511:524 arg1 EPS 526:528 polysaccharide EPS 511:528 polysaccharide EPS (wild-type and mutant P. aeruginosa) 511:565 Biofilms with protein-based (Pseudomonas putida) and polysaccharide based EPS (Pseudomonas aeruginosa), as well as biofilms with varied amount of polysaccharide EPS (wild-type and mutant P. aeruginosa), were compared. 24575887 3 62 with reactivity 597:606 arg1 monochloramine 631:644 monochloramine 631:644 monochloramine 631:644 The different reactivity of EPS components with monochloramine influenced disinfectant penetration, biofilm inactivation, as well as the viability of detached clusters. 24575887 5 63 theme P. 1014:1015 arg1 EPS 1024:1026 P. putida EPS 1014:1026 P. putida EPS 1014:1026 The reaction with proteins in P. putida EPS multiplied both the time and the monochloramine mass required to achieve a full biofilm penetration. 24575887 2 64 dep protein-based 379:391 arg1 aeruginosa 456:465 Pseudomonas aeruginosa 444:465 Pseudomonas aeruginosa 444:465 Biofilms with protein-based (Pseudomonas putida) and polysaccharide based EPS (Pseudomonas aeruginosa), as well as biofilms with varied amount of polysaccharide EPS (wild-type and mutant P. aeruginosa), were compared. 24575887 2 64 dep protein-based 379:391 arg1 putida 406:411 Pseudomonas putida 394:411 Pseudomonas putida 394:411 Biofilms with protein-based (Pseudomonas putida) and polysaccharide based EPS (Pseudomonas aeruginosa), as well as biofilms with varied amount of polysaccharide EPS (wild-type and mutant P. aeruginosa), were compared. 24575887 0 65 theme clusters 125:132 arg1 disinfection 88:99 the disinfection 84:99 the disinfection of biofilm and detached clusters 84:132 Selective reactivity of monochloramine with extracellular matrix components affects the disinfection of biofilm and detached clusters. 24575887 8 66 dep detached 1701:1708 arg1 % 1731:1731 over 70% 1724:1731 over 70% for P. putida 1724:1745 Furthermore, the persistence of bacterial cells detached from biofilm (over 70% for P. putida and ∼40% for polysaccharide producing P. aeruginosa) suggested that currently recommended monochloramine residual levels may underestimate the risk of water quality deterioration caused by biofilm detachment. 24575887 8 66 dep detached 1701:1708 arg1 % 1754:1754 ∼40% 1751:1754 ∼40% for polysaccharide producing P. aeruginosa 1751:1797 Furthermore, the persistence of bacterial cells detached from biofilm (over 70% for P. putida and ∼40% for polysaccharide producing P. aeruginosa) suggested that currently recommended monochloramine residual levels may underestimate the risk of water quality deterioration caused by biofilm detachment. 24575887 8 67 theme quality 1904:1910 arg1 deterioration 1912:1924 water quality deterioration 1898:1924 water quality deterioration 1898:1924 Furthermore, the persistence of bacterial cells detached from biofilm (over 70% for P. putida and ∼40% for polysaccharide producing P. aeruginosa) suggested that currently recommended monochloramine residual levels may underestimate the risk of water quality deterioration caused by biofilm detachment. 24575887 6 68 theme Cell 1129:1132 arg1 viability 1134:1142 Cell viability 1129:1142 Cell viability in biofilms 1129:1154 Cell viability in biofilms was also spatially influenced by monochloramine diffusion and reaction within biofilms, showing a lower survival in the surface section and a higher persistence in the middle section of the P. putida biofilm compared to the P. aeruginosa biofilms. 24575887 2 69 theme polysaccharide 418:431 arg1 EPS 439:441 protein-based (Pseudomonas putida) and polysaccharide based EPS 379:441 EPS 439:441 Biofilms with protein-based (Pseudomonas putida) and polysaccharide based EPS (Pseudomonas aeruginosa), as well as biofilms with varied amount of polysaccharide EPS (wild-type and mutant P. aeruginosa), were compared. 24575887 4 70 theme transport 767:775 arg1 profiling 777:785 Monochloramine transport profiling 752:785 Monochloramine transport profiling measured by a chloramine-sensitive microelectrode 752:835 Monochloramine transport profiling measured by a chloramine-sensitive microelectrode revealed a broader diffusion boundary layer between bulk and biofilm surface in the P. putida biofilm compared to those of P. aeruginosa biofilms. 24575887 0 71 theme monochloramine 24:37 arg1 reactivity 10:19 Selective reactivity 0:19 Selective reactivity of monochloramine with extracellular matrix components 0:74 Selective reactivity of monochloramine with extracellular matrix components affects the disinfection of biofilm and detached clusters. 24575887 2 72 dep wild-type 531:539 arg1 aeruginosa 555:564 P. aeruginosa 552:564 P. aeruginosa 552:564 Biofilms with protein-based (Pseudomonas putida) and polysaccharide based EPS (Pseudomonas aeruginosa), as well as biofilms with varied amount of polysaccharide EPS (wild-type and mutant P. aeruginosa), were compared. 24575887 8 73 theme biofilm 1936:1942 arg1 detachment 1944:1953 biofilm detachment 1936:1953 biofilm detachment 1936:1953 Furthermore, the persistence of bacterial cells detached from biofilm (over 70% for P. putida and ∼40% for polysaccharide producing P. aeruginosa) suggested that currently recommended monochloramine residual levels may underestimate the risk of water quality deterioration caused by biofilm detachment. 24575887 0 74 theme extracellular 44:56 arg1 components 65:74 extracellular matrix components 44:74 extracellular matrix components 44:74 Selective reactivity of monochloramine with extracellular matrix components affects the disinfection of biofilm and detached clusters. 24575887 1 75 theme selective 308:316 arg1 reactivity 318:327 a selective reactivity 306:327 a selective reactivity with proteins 306:341 The efficiency of monochloramine disinfection was dependent on the quantity and composition of extracellular polymeric substances (EPS) in biofilms, as monochloramine has a selective reactivity with proteins over polysaccharides. 24575887 3 76 theme disinfectant 657:668 arg1 penetration 670:680 disinfectant penetration 657:680 disinfectant penetration 657:680 The different reactivity of EPS components with monochloramine influenced disinfectant penetration, biofilm inactivation, as well as the viability of detached clusters. 24575887 6 77 theme aeruginosa 1383:1392 arg1 biofilms 1394:1401 the P. aeruginosa biofilms 1376:1401 the P. aeruginosa biofilms 1376:1401 Cell viability in biofilms was also spatially influenced by monochloramine diffusion and reaction within biofilms, showing a lower survival in the surface section and a higher persistence in the middle section of the P. putida biofilm compared to the P. aeruginosa biofilms. 24575887 2 78 with Biofilms 365:372 arg1 biofilms 480:487 biofilms 480:487 biofilms with varied amount of polysaccharide EPS (wild-type and mutant P. aeruginosa) 480:565 Biofilms with protein-based (Pseudomonas putida) and polysaccharide based EPS (Pseudomonas aeruginosa), as well as biofilms with varied amount of polysaccharide EPS (wild-type and mutant P. aeruginosa), were compared. 24575887 2 78 with Biofilms 365:372 arg1 EPS 439:441 protein-based (Pseudomonas putida) and polysaccharide based EPS 379:441 EPS 439:441 Biofilms with protein-based (Pseudomonas putida) and polysaccharide based EPS (Pseudomonas aeruginosa), as well as biofilms with varied amount of polysaccharide EPS (wild-type and mutant P. aeruginosa), were compared. 24575887 2 78 with Biofilms 365:372 arg1 protein-based 379:391 protein-based 379:391 protein-based 379:391 Biofilms with protein-based (Pseudomonas putida) and polysaccharide based EPS (Pseudomonas aeruginosa), as well as biofilms with varied amount of polysaccharide EPS (wild-type and mutant P. aeruginosa), were compared. 24575887 1 79 from quantity 202:209 arg1 biofilms 274:281 biofilms 274:281 biofilms 274:281 The efficiency of monochloramine disinfection was dependent on the quantity and composition of extracellular polymeric substances (EPS) in biofilms, as monochloramine has a selective reactivity with proteins over polysaccharides. 24575887 4 80 theme bulk 889:892 arg1 surface 906:912 bulk and biofilm surface 889:912 surface 906:912 Monochloramine transport profiling measured by a chloramine-sensitive microelectrode revealed a broader diffusion boundary layer between bulk and biofilm surface in the P. putida biofilm compared to those of P. aeruginosa biofilms. 24575887 0 81 with reactivity 10:19 arg1 components 65:74 extracellular matrix components 44:74 extracellular matrix components 44:74 Selective reactivity of monochloramine with extracellular matrix components affects the disinfection of biofilm and detached clusters. 24575887 2 82 dep EPS 526:528 arg1 wild-type 531:539 wild-type 531:539 wild-type 531:539 Biofilms with protein-based (Pseudomonas putida) and polysaccharide based EPS (Pseudomonas aeruginosa), as well as biofilms with varied amount of polysaccharide EPS (wild-type and mutant P. aeruginosa), were compared. 24575887 2 82 dep EPS 526:528 arg1 mutant 545:550 mutant 545:550 mutant 545:550 Biofilms with protein-based (Pseudomonas putida) and polysaccharide based EPS (Pseudomonas aeruginosa), as well as biofilms with varied amount of polysaccharide EPS (wild-type and mutant P. aeruginosa), were compared. 24575887 8 83 theme cells 1695:1699 arg1 persistence 1670:1680 the persistence 1666:1680 the persistence of bacterial cells detached from biofilm (over 70% for P. putida and ∼40% for polysaccharide producing P. aeruginosa) 1666:1798 Furthermore, the persistence of bacterial cells detached from biofilm (over 70% for P. putida and ∼40% for polysaccharide producing P. aeruginosa) suggested that currently recommended monochloramine residual levels may underestimate the risk of water quality deterioration caused by biofilm detachment. 24575887 5 84 from reaction 988:995 arg1 EPS 1024:1026 P. putida EPS 1014:1026 P. putida EPS 1014:1026 The reaction with proteins in P. putida EPS multiplied both the time and the monochloramine mass required to achieve a full biofilm penetration. 24575887 4 85 theme diffusion 856:864 arg1 layer 875:879 a broader diffusion boundary layer 846:879 a broader diffusion boundary layer between bulk and biofilm surface 846:912 Monochloramine transport profiling measured by a chloramine-sensitive microelectrode revealed a broader diffusion boundary layer between bulk and biofilm surface in the P. putida biofilm compared to those of P. aeruginosa biofilms. 24556634 8 0 theme phenotypic 1024:1033 arg1 properties 1035:1044 the genetic and phenotypic properties 1008:1044 the genetic and phenotypic properties 1008:1044 Since the genetic and phenotypic properties suggest that strain UasXn-3T represents a novel species, we propose the name Bacteroides luti sp. 24556634 8 1 theme strain 1059:1064 arg1 UasXn-3T 1066:1073 strain UasXn-3T 1059:1073 strain UasXn-3T 1059:1073 Since the genetic and phenotypic properties suggest that strain UasXn-3T represents a novel species, we propose the name Bacteroides luti sp. 24556634 4 2 theme pH 488:489 arg1 6.5-7.0 491:497 pH 6.5-7.0 488:497 pH 6.5-7.0 488:497 The optimal temperature for growth was 37-40 °C and the optimal pH for growth was pH 6.5-7.0. 24556634 4 2 theme pH 488:489 arg1 pH 470:471 the optimal pH 458:471 the optimal pH for growth 458:482 The optimal temperature for growth was 37-40 °C and the optimal pH for growth was pH 6.5-7.0. 24556634 10 3 theme type 1153:1156 arg1 strain 1158:1163 The type strain 1149:1163 The type strain 1149:1163 The type strain is UasXn-3T (=JCM 19020T=DSM 26991T). 24556634 10 3 theme type 1153:1156 arg1 UasXn-3T 1168:1175 UasXn-3T 1168:1175 UasXn-3T (=JCM 19020T=DSM 26991T) 1168:1200 The type strain is UasXn-3T (=JCM 19020T=DSM 26991T). 24556634 7 4 dep oleiciplenus 890:901 arg1 similarities 973:984 sequence similarities 964:984 sequence similarities of 91.3-91.6% 964:998 On the basis of comparative 16S rRNA gene sequence analysis, strain UasXn-3T was identified as a member of the genus Bacteroides and most closely related to Bacteroides oleiciplenus, B. intestinalis, B. cellulosilyticus and B. graminisolvens (sequence similarities of 91.3-91.6%). 24556634 2 5 theme blanket 271:277 arg1 reactor 279:285 a mesophilic upflow anaerobic sludge blanket reactor 234:285 a mesophilic upflow anaerobic sludge blanket reactor 234:285 A mesophilic, anaerobic, cellulolytic and xylanolytic strain, UasXn-3T, was isolated from anaerobic granular sludge in a mesophilic upflow anaerobic sludge blanket reactor, which was used to treat municipal sewage. 24556634 2 6 theme sludge 264:269 arg1 reactor 279:285 a mesophilic upflow anaerobic sludge blanket reactor 234:285 a mesophilic upflow anaerobic sludge blanket reactor 234:285 A mesophilic, anaerobic, cellulolytic and xylanolytic strain, UasXn-3T, was isolated from anaerobic granular sludge in a mesophilic upflow anaerobic sludge blanket reactor, which was used to treat municipal sewage. 24556634 7 7 theme strain 782:787 arg1 member 818:823 a member 816:823 a member of the genus Bacteroides 816:848 On the basis of comparative 16S rRNA gene sequence analysis, strain UasXn-3T was identified as a member of the genus Bacteroides and most closely related to Bacteroides oleiciplenus, B. intestinalis, B. cellulosilyticus and B. graminisolvens (sequence similarities of 91.3-91.6%). 24556634 7 7 theme strain 782:787 arg1 UasXn-3T 789:796 strain UasXn-3T 782:796 strain UasXn-3T 782:796 On the basis of comparative 16S rRNA gene sequence analysis, strain UasXn-3T was identified as a member of the genus Bacteroides and most closely related to Bacteroides oleiciplenus, B. intestinalis, B. cellulosilyticus and B. graminisolvens (sequence similarities of 91.3-91.6%). 24556634 8 8 theme luti 1135:1138 arg1 sp 1140:1141 the name Bacteroides luti sp 1114:1141 the name Bacteroides luti sp 1114:1141 Since the genetic and phenotypic properties suggest that strain UasXn-3T represents a novel species, we propose the name Bacteroides luti sp. 24556634 2 9 theme anaerobic 254:262 arg1 reactor 279:285 a mesophilic upflow anaerobic sludge blanket reactor 234:285 a mesophilic upflow anaerobic sludge blanket reactor 234:285 A mesophilic, anaerobic, cellulolytic and xylanolytic strain, UasXn-3T, was isolated from anaerobic granular sludge in a mesophilic upflow anaerobic sludge blanket reactor, which was used to treat municipal sewage. 24556634 7 10 theme sequence 763:770 arg1 analysis 772:779 comparative 16S rRNA gene sequence analysis 737:779 comparative 16S rRNA gene sequence analysis 737:779 On the basis of comparative 16S rRNA gene sequence analysis, strain UasXn-3T was identified as a member of the genus Bacteroides and most closely related to Bacteroides oleiciplenus, B. intestinalis, B. cellulosilyticus and B. graminisolvens (sequence similarities of 91.3-91.6%). 24556634 2 11 attach isolated 191:198 arg1 sludge 224:229 anaerobic granular sludge 205:229 anaerobic granular sludge 205:229 A mesophilic, anaerobic, cellulolytic and xylanolytic strain, UasXn-3T, was isolated from anaerobic granular sludge in a mesophilic upflow anaerobic sludge blanket reactor, which was used to treat municipal sewage. 24556634 2 11 attach isolated 191:198 arg2 UasXn-3T 177:184 UasXn-3T 177:184 UasXn-3T 177:184 A mesophilic, anaerobic, cellulolytic and xylanolytic strain, UasXn-3T, was isolated from anaerobic granular sludge in a mesophilic upflow anaerobic sludge blanket reactor, which was used to treat municipal sewage. 24556634 2 11 attach isolated 191:198 arg2 strain 169:174 A mesophilic, anaerobic, cellulolytic and xylanolytic strain 115:174 A mesophilic, anaerobic, cellulolytic and xylanolytic strain 115:174 A mesophilic, anaerobic, cellulolytic and xylanolytic strain, UasXn-3T, was isolated from anaerobic granular sludge in a mesophilic upflow anaerobic sludge blanket reactor, which was used to treat municipal sewage. 24556634 0 12 theme luti 12:15 arg1 sp 17:18 Bacteroides luti sp 0:18 Bacteroides luti sp. 0:19 Bacteroides luti sp. 24556634 4 13 theme optimal 462:468 arg1 6.5-7.0 491:497 pH 6.5-7.0 488:497 pH 6.5-7.0 488:497 The optimal temperature for growth was 37-40 °C and the optimal pH for growth was pH 6.5-7.0. 24556634 4 13 theme optimal 462:468 arg1 pH 470:471 the optimal pH 458:471 the optimal pH for growth 458:482 The optimal temperature for growth was 37-40 °C and the optimal pH for growth was pH 6.5-7.0. 24556634 7 14 theme analysis 772:779 arg1 basis 728:732 the basis 724:732 the basis of comparative 16S rRNA gene sequence analysis 724:779 On the basis of comparative 16S rRNA gene sequence analysis, strain UasXn-3T was identified as a member of the genus Bacteroides and most closely related to Bacteroides oleiciplenus, B. intestinalis, B. cellulosilyticus and B. graminisolvens (sequence similarities of 91.3-91.6%). 24556634 0 15 theme Bacteroides 0:10 arg1 sp 17:18 Bacteroides luti sp 0:18 Bacteroides luti sp. 0:19 Bacteroides luti sp. 24556634 8 16 theme genetic 1012:1018 arg1 properties 1035:1044 the genetic and phenotypic properties 1008:1044 the genetic and phenotypic properties 1008:1044 Since the genetic and phenotypic properties suggest that strain UasXn-3T represents a novel species, we propose the name Bacteroides luti sp. 24556634 6 17 theme mol 715:717 arg1 % 718:718 44.4 mol% 710:718 44.4 mol% 710:718 The DNA G+C content was 44.4 mol%. 24556634 6 17 theme mol 715:717 arg1 content 698:704 The DNA G+C content 686:704 The DNA G+C content 686:704 The DNA G+C content was 44.4 mol%. 24556634 7 18 theme rRNA 753:756 arg1 analysis 772:779 comparative 16S rRNA gene sequence analysis 737:779 comparative 16S rRNA gene sequence analysis 737:779 On the basis of comparative 16S rRNA gene sequence analysis, strain UasXn-3T was identified as a member of the genus Bacteroides and most closely related to Bacteroides oleiciplenus, B. intestinalis, B. cellulosilyticus and B. graminisolvens (sequence similarities of 91.3-91.6%). 24556634 7 19 theme genus 832:836 arg1 Bacteroides 838:848 the genus Bacteroides 828:848 the genus Bacteroides 828:848 On the basis of comparative 16S rRNA gene sequence analysis, strain UasXn-3T was identified as a member of the genus Bacteroides and most closely related to Bacteroides oleiciplenus, B. intestinalis, B. cellulosilyticus and B. graminisolvens (sequence similarities of 91.3-91.6%). 24556634 7 20 theme Bacteroides 838:848 arg1 member 818:823 a member 816:823 a member of the genus Bacteroides 816:848 On the basis of comparative 16S rRNA gene sequence analysis, strain UasXn-3T was identified as a member of the genus Bacteroides and most closely related to Bacteroides oleiciplenus, B. intestinalis, B. cellulosilyticus and B. graminisolvens (sequence similarities of 91.3-91.6%). 24556634 7 20 theme Bacteroides 838:848 arg1 UasXn-3T 789:796 strain UasXn-3T 782:796 strain UasXn-3T 782:796 On the basis of comparative 16S rRNA gene sequence analysis, strain UasXn-3T was identified as a member of the genus Bacteroides and most closely related to Bacteroides oleiciplenus, B. intestinalis, B. cellulosilyticus and B. graminisolvens (sequence similarities of 91.3-91.6%). 24556634 7 21 theme gene 758:761 arg1 analysis 772:779 comparative 16S rRNA gene sequence analysis 737:779 comparative 16S rRNA gene sequence analysis 737:779 On the basis of comparative 16S rRNA gene sequence analysis, strain UasXn-3T was identified as a member of the genus Bacteroides and most closely related to Bacteroides oleiciplenus, B. intestinalis, B. cellulosilyticus and B. graminisolvens (sequence similarities of 91.3-91.6%). 24556634 7 22 theme % 998:998 arg1 similarities 973:984 sequence similarities 964:984 sequence similarities of 91.3-91.6% 964:998 On the basis of comparative 16S rRNA gene sequence analysis, strain UasXn-3T was identified as a member of the genus Bacteroides and most closely related to Bacteroides oleiciplenus, B. intestinalis, B. cellulosilyticus and B. graminisolvens (sequence similarities of 91.3-91.6%). 24556634 1 23 theme methanogenic 94:105 arg1 sludge 107:112 methanogenic sludge 94:112 methanogenic sludge 94:112 nov., an anaerobic, cellulolytic and xylanolytic bacterium isolated from methanogenic sludge. 24556634 7 24 theme comparative 737:747 arg1 analysis 772:779 comparative 16S rRNA gene sequence analysis 737:779 comparative 16S rRNA gene sequence analysis 737:779 On the basis of comparative 16S rRNA gene sequence analysis, strain UasXn-3T was identified as a member of the genus Bacteroides and most closely related to Bacteroides oleiciplenus, B. intestinalis, B. cellulosilyticus and B. graminisolvens (sequence similarities of 91.3-91.6%). 24556634 1 25 dep anaerobic 30:38 arg1 xylanolytic 58:68 xylanolytic 58:68 xylanolytic 58:68 nov., an anaerobic, cellulolytic and xylanolytic bacterium isolated from methanogenic sludge. 24556634 1 25 dep anaerobic 30:38 arg1 cellulolytic 41:52 cellulolytic 41:52 cellulolytic 41:52 nov., an anaerobic, cellulolytic and xylanolytic bacterium isolated from methanogenic sludge. 24556634 8 26 theme Bacteroides 1123:1133 arg1 sp 1140:1141 the name Bacteroides luti sp 1114:1141 the name Bacteroides luti sp 1114:1141 Since the genetic and phenotypic properties suggest that strain UasXn-3T represents a novel species, we propose the name Bacteroides luti sp. 24556634 10 27 theme 19020T=DSM 1183:1192 arg1 26991T 1194:1199 =JCM 19020T=DSM 26991T 1178:1199 =JCM 19020T=DSM 26991T 1178:1199 The type strain is UasXn-3T (=JCM 19020T=DSM 26991T). 24556634 10 27 theme 19020T=DSM 1183:1192 arg1 UasXn-3T 1168:1175 UasXn-3T 1168:1175 UasXn-3T (=JCM 19020T=DSM 26991T) 1168:1200 The type strain is UasXn-3T (=JCM 19020T=DSM 26991T). 24556634 7 28 theme 16S 749:751 arg1 analysis 772:779 comparative 16S rRNA gene sequence analysis 737:779 comparative 16S rRNA gene sequence analysis 737:779 On the basis of comparative 16S rRNA gene sequence analysis, strain UasXn-3T was identified as a member of the genus Bacteroides and most closely related to Bacteroides oleiciplenus, B. intestinalis, B. cellulosilyticus and B. graminisolvens (sequence similarities of 91.3-91.6%). 24556634 8 29 theme name 1118:1121 arg1 sp 1140:1141 the name Bacteroides luti sp 1114:1141 the name Bacteroides luti sp 1114:1141 Since the genetic and phenotypic properties suggest that strain UasXn-3T represents a novel species, we propose the name Bacteroides luti sp. 24556634 2 30 theme granular 215:222 arg1 sludge 224:229 anaerobic granular sludge 205:229 anaerobic granular sludge 205:229 A mesophilic, anaerobic, cellulolytic and xylanolytic strain, UasXn-3T, was isolated from anaerobic granular sludge in a mesophilic upflow anaerobic sludge blanket reactor, which was used to treat municipal sewage. 24556634 8 31 theme novel 1088:1092 arg1 species 1094:1100 a novel species 1086:1100 a novel species 1086:1100 Since the genetic and phenotypic properties suggest that strain UasXn-3T represents a novel species, we propose the name Bacteroides luti sp. 24556634 2 32 theme anaerobic 205:213 arg1 sludge 224:229 anaerobic granular sludge 205:229 anaerobic granular sludge 205:229 A mesophilic, anaerobic, cellulolytic and xylanolytic strain, UasXn-3T, was isolated from anaerobic granular sludge in a mesophilic upflow anaerobic sludge blanket reactor, which was used to treat municipal sewage. 24556634 3 33 theme non-spore-forming 382:398 arg1 rods 400:403 non-spore-forming rods 382:403 non-spore-forming rods 382:403 The cells were Gram-stain-negative, non-motile, and non-spore-forming rods. 24556634 2 34 dep mesophilic 117:126 arg1 anaerobic 129:137 anaerobic 129:137 anaerobic 129:137 A mesophilic, anaerobic, cellulolytic and xylanolytic strain, UasXn-3T, was isolated from anaerobic granular sludge in a mesophilic upflow anaerobic sludge blanket reactor, which was used to treat municipal sewage. 24556634 2 34 dep mesophilic 117:126 arg1 xylanolytic 157:167 xylanolytic 157:167 xylanolytic 157:167 A mesophilic, anaerobic, cellulolytic and xylanolytic strain, UasXn-3T, was isolated from anaerobic granular sludge in a mesophilic upflow anaerobic sludge blanket reactor, which was used to treat municipal sewage. 24556634 2 34 dep mesophilic 117:126 arg1 cellulolytic 140:151 cellulolytic 140:151 cellulolytic 140:151 A mesophilic, anaerobic, cellulolytic and xylanolytic strain, UasXn-3T, was isolated from anaerobic granular sludge in a mesophilic upflow anaerobic sludge blanket reactor, which was used to treat municipal sewage. 24556634 7 35 theme sequence 964:971 arg1 similarities 973:984 sequence similarities 964:984 sequence similarities of 91.3-91.6% 964:998 On the basis of comparative 16S rRNA gene sequence analysis, strain UasXn-3T was identified as a member of the genus Bacteroides and most closely related to Bacteroides oleiciplenus, B. intestinalis, B. cellulosilyticus and B. graminisolvens (sequence similarities of 91.3-91.6%). 24556634 4 36 theme optimal 410:416 arg1 temperature 418:428 The optimal temperature 406:428 The optimal temperature for growth 406:439 The optimal temperature for growth was 37-40 °C and the optimal pH for growth was pH 6.5-7.0. 24556634 4 36 theme optimal 410:416 arg1 °C 451:452 37-40 °C 445:452 37-40 °C 445:452 The optimal temperature for growth was 37-40 °C and the optimal pH for growth was pH 6.5-7.0. 24556634 6 37 theme G+C 694:696 arg1 % 718:718 44.4 mol% 710:718 44.4 mol% 710:718 The DNA G+C content was 44.4 mol%. 24556634 6 37 theme G+C 694:696 arg1 content 698:704 The DNA G+C content 686:704 The DNA G+C content 686:704 The DNA G+C content was 44.4 mol%. 24556634 2 38 theme municipal 312:320 arg1 sewage 322:327 municipal sewage 312:327 municipal sewage 312:327 A mesophilic, anaerobic, cellulolytic and xylanolytic strain, UasXn-3T, was isolated from anaerobic granular sludge in a mesophilic upflow anaerobic sludge blanket reactor, which was used to treat municipal sewage. 24556634 2 39 theme upflow 247:252 arg1 reactor 279:285 a mesophilic upflow anaerobic sludge blanket reactor 234:285 a mesophilic upflow anaerobic sludge blanket reactor 234:285 A mesophilic, anaerobic, cellulolytic and xylanolytic strain, UasXn-3T, was isolated from anaerobic granular sludge in a mesophilic upflow anaerobic sludge blanket reactor, which was used to treat municipal sewage. 24556634 5 40 theme several 530:536 arg1 raffinose 653:661 raffinose 653:661 raffinose 653:661 Strain UasXn-3T could grow on several polysaccharides and sugars, including cellulose, cellobiose, xylan, xylose, glucose, fructose, arabinose, mannose, raffinose, trehalose and starch. 24556634 5 40 theme several 530:536 arg1 xylan 599:603 xylan 599:603 xylan 599:603 Strain UasXn-3T could grow on several polysaccharides and sugars, including cellulose, cellobiose, xylan, xylose, glucose, fructose, arabinose, mannose, raffinose, trehalose and starch. 24556634 5 40 theme several 530:536 arg1 trehalose 664:672 trehalose 664:672 trehalose 664:672 Strain UasXn-3T could grow on several polysaccharides and sugars, including cellulose, cellobiose, xylan, xylose, glucose, fructose, arabinose, mannose, raffinose, trehalose and starch. 24556634 5 40 theme several 530:536 arg1 xylose 606:611 xylose 606:611 xylose 606:611 Strain UasXn-3T could grow on several polysaccharides and sugars, including cellulose, cellobiose, xylan, xylose, glucose, fructose, arabinose, mannose, raffinose, trehalose and starch. 24556634 5 40 theme several 530:536 arg1 arabinose 633:641 arabinose 633:641 arabinose 633:641 Strain UasXn-3T could grow on several polysaccharides and sugars, including cellulose, cellobiose, xylan, xylose, glucose, fructose, arabinose, mannose, raffinose, trehalose and starch. 24556634 5 40 theme several 530:536 arg1 cellulose 576:584 cellulose 576:584 cellulose 576:584 Strain UasXn-3T could grow on several polysaccharides and sugars, including cellulose, cellobiose, xylan, xylose, glucose, fructose, arabinose, mannose, raffinose, trehalose and starch. 24556634 5 40 theme several 530:536 arg1 mannose 644:650 mannose 644:650 mannose 644:650 Strain UasXn-3T could grow on several polysaccharides and sugars, including cellulose, cellobiose, xylan, xylose, glucose, fructose, arabinose, mannose, raffinose, trehalose and starch. 24556634 5 40 theme several 530:536 arg1 starch 678:683 starch 678:683 starch 678:683 Strain UasXn-3T could grow on several polysaccharides and sugars, including cellulose, cellobiose, xylan, xylose, glucose, fructose, arabinose, mannose, raffinose, trehalose and starch. 24556634 5 40 theme several 530:536 arg1 cellobiose 587:596 cellobiose 587:596 cellobiose 587:596 Strain UasXn-3T could grow on several polysaccharides and sugars, including cellulose, cellobiose, xylan, xylose, glucose, fructose, arabinose, mannose, raffinose, trehalose and starch. 24556634 5 40 theme several 530:536 arg1 glucose 614:620 glucose 614:620 glucose 614:620 Strain UasXn-3T could grow on several polysaccharides and sugars, including cellulose, cellobiose, xylan, xylose, glucose, fructose, arabinose, mannose, raffinose, trehalose and starch. 24556634 5 40 theme several 530:536 arg1 polysaccharides 538:552 several polysaccharides 530:552 several polysaccharides 530:552 Strain UasXn-3T could grow on several polysaccharides and sugars, including cellulose, cellobiose, xylan, xylose, glucose, fructose, arabinose, mannose, raffinose, trehalose and starch. 24556634 5 40 theme several 530:536 arg1 fructose 623:630 fructose 623:630 fructose 623:630 Strain UasXn-3T could grow on several polysaccharides and sugars, including cellulose, cellobiose, xylan, xylose, glucose, fructose, arabinose, mannose, raffinose, trehalose and starch. 24556634 6 41 theme DNA 690:692 arg1 % 718:718 44.4 mol% 710:718 44.4 mol% 710:718 The DNA G+C content was 44.4 mol%. 24556634 6 41 theme DNA 690:692 arg1 content 698:704 The DNA G+C content 686:704 The DNA G+C content 686:704 The DNA G+C content was 44.4 mol%. 24556634 2 42 theme mesophilic 236:245 arg1 reactor 279:285 a mesophilic upflow anaerobic sludge blanket reactor 234:285 a mesophilic upflow anaerobic sludge blanket reactor 234:285 A mesophilic, anaerobic, cellulolytic and xylanolytic strain, UasXn-3T, was isolated from anaerobic granular sludge in a mesophilic upflow anaerobic sludge blanket reactor, which was used to treat municipal sewage. 24556634 10 43 theme =JCM 1178:1181 arg1 26991T 1194:1199 =JCM 19020T=DSM 26991T 1178:1199 =JCM 19020T=DSM 26991T 1178:1199 The type strain is UasXn-3T (=JCM 19020T=DSM 26991T). 24556634 10 43 theme =JCM 1178:1181 arg1 UasXn-3T 1168:1175 UasXn-3T 1168:1175 UasXn-3T (=JCM 19020T=DSM 26991T) 1168:1200 The type strain is UasXn-3T (=JCM 19020T=DSM 26991T). 24556634 2 44 used used 298:301 arg2 reactor 279:285 a mesophilic upflow anaerobic sludge blanket reactor 234:285 a mesophilic upflow anaerobic sludge blanket reactor 234:285 A mesophilic, anaerobic, cellulolytic and xylanolytic strain, UasXn-3T, was isolated from anaerobic granular sludge in a mesophilic upflow anaerobic sludge blanket reactor, which was used to treat municipal sewage. 24556634 2 45 theme mesophilic 117:126 arg1 strain 169:174 A mesophilic, anaerobic, cellulolytic and xylanolytic strain 115:174 A mesophilic, anaerobic, cellulolytic and xylanolytic strain 115:174 A mesophilic, anaerobic, cellulolytic and xylanolytic strain, UasXn-3T, was isolated from anaerobic granular sludge in a mesophilic upflow anaerobic sludge blanket reactor, which was used to treat municipal sewage. 24556634 2 45 theme mesophilic 117:126 arg1 UasXn-3T 177:184 UasXn-3T 177:184 UasXn-3T 177:184 A mesophilic, anaerobic, cellulolytic and xylanolytic strain, UasXn-3T, was isolated from anaerobic granular sludge in a mesophilic upflow anaerobic sludge blanket reactor, which was used to treat municipal sewage. 24556634 1 46 theme anaerobic 30:38 arg1 nov. 21:24 nov. 21:24 nov. 21:24 nov., an anaerobic, cellulolytic and xylanolytic bacterium isolated from methanogenic sludge. 24556634 1 46 theme anaerobic 30:38 arg1 bacterium 70:78 an anaerobic, cellulolytic and xylanolytic bacterium 27:78 an anaerobic, cellulolytic and xylanolytic bacterium 27:78 nov., an anaerobic, cellulolytic and xylanolytic bacterium isolated from methanogenic sludge. 24556634 5 47 theme Strain 500:505 arg1 UasXn-3T 507:514 Strain UasXn-3T 500:514 Strain UasXn-3T 500:514 Strain UasXn-3T could grow on several polysaccharides and sugars, including cellulose, cellobiose, xylan, xylose, glucose, fructose, arabinose, mannose, raffinose, trehalose and starch. 28511646 0 0 from due 33:35 arg1 model 80:84 a spatial model 70:84 a spatial model of gut microbial metabolism 70:112 Emergence of microbial diversity due to cross-feeding interactions in a spatial model of gut microbial metabolism. 28511646 2 1 theme digestive 330:338 arg1 enzymes 340:346 our own digestive enzymes 322:346 our own digestive enzymes 322:346 Together, these microbial species form a complex food web that can break down nutrient sources that our own digestive enzymes cannot handle, including complex polysaccharides, producing short chain fatty acids and additional metabolites, e.g., vitamin K. Microbial diversity is important for colonic health: Changes in the composition of the microbiota have been associated with inflammatory bowel disease, diabetes, obesity and Crohn's disease, and make the microbiota more vulnerable to infestation by harmful species, e.g., Clostridium difficile. 28511646 3 2 dep gut-like 989:996 arg1 tubular 999:1005 tubular 999:1005 tubular 999:1005 To get a grip on the controlling factors of microbial diversity in the gut, we here propose a multi-scale, spatiotemporal dynamic flux-balance analysis model to study the emergence of metabolic diversity in a spatial gut-like, tubular environment. 28511646 3 3 from diversity 826:834 arg1 gut 843:845 the gut 839:845 the gut 839:845 To get a grip on the controlling factors of microbial diversity in the gut, we here propose a multi-scale, spatiotemporal dynamic flux-balance analysis model to study the emergence of metabolic diversity in a spatial gut-like, tubular environment. 28511646 9 4 theme intestinal 2090:2099 arg1 wall 2101:2104 the intestinal wall 2086:2104 the intestinal wall 2086:2104 It can be extended to include, e.g., complex nutrient sources, and host-microbiota interactions via the intestinal wall. 28511646 8 5 theme in 1851:1852 arg1 tool 1880:1883 a helpful tool 1870:1883 a helpful tool in systems biology to predict and explain the controlling factors of microbial diversity in the gut 1870:1983 CONCLUSIONS In conclusion, this in silico model is a helpful tool in systems biology to predict and explain the controlling factors of microbial diversity in the gut. 28511646 8 5 theme in 1851:1852 arg1 model 1861:1865 this in silico model 1846:1865 this in silico model 1846:1865 CONCLUSIONS In conclusion, this in silico model is a helpful tool in systems biology to predict and explain the controlling factors of microbial diversity in the gut. 28511646 3 6 theme metabolic 956:964 arg1 diversity 966:974 metabolic diversity 956:974 metabolic diversity 956:974 To get a grip on the controlling factors of microbial diversity in the gut, we here propose a multi-scale, spatiotemporal dynamic flux-balance analysis model to study the emergence of metabolic diversity in a spatial gut-like, tubular environment. 28511646 2 7 theme harmful 726:732 arg1 species 734:740 harmful species 726:740 harmful species 726:740 Together, these microbial species form a complex food web that can break down nutrient sources that our own digestive enzymes cannot handle, including complex polysaccharides, producing short chain fatty acids and additional metabolites, e.g., vitamin K. Microbial diversity is important for colonic health: Changes in the composition of the microbiota have been associated with inflammatory bowel disease, diabetes, obesity and Crohn's disease, and make the microbiota more vulnerable to infestation by harmful species, e.g., Clostridium difficile. 28511646 1 8 contain contains 140:147 arg2 bacteria 168:175 approximately 1014 bacteria 149:175 approximately 1014 bacteria 149:175 BACKGROUND The human gut contains approximately 1014 bacteria, belonging to hundreds of different species. 28511646 1 8 contain contains 140:147 arg1 gut 136:138 The human gut 126:138 The human gut 126:138 BACKGROUND The human gut contains approximately 1014 bacteria, belonging to hundreds of different species. 28511646 2 9 theme complex 263:269 arg1 web 276:278 a complex food web 261:278 a complex food web that can break down nutrient sources that our own digestive enzymes cannot handle, including complex polysaccharides, producing short chain fatty acids and additional metabolites, e.g., vitamin K. Microbial diversity is important for colonic health: Changes in the composition of the microbiota have been associated with inflammatory bowel disease, diabetes, obesity and Crohn's disease, and make the microbiota more vulnerable to infestation by harmful species, e.g., Clostridium difficile 261:769 Together, these microbial species form a complex food web that can break down nutrient sources that our own digestive enzymes cannot handle, including complex polysaccharides, producing short chain fatty acids and additional metabolites, e.g., vitamin K. Microbial diversity is important for colonic health: Changes in the composition of the microbiota have been associated with inflammatory bowel disease, diabetes, obesity and Crohn's disease, and make the microbiota more vulnerable to infestation by harmful species, e.g., Clostridium difficile. 28511646 6 10 theme microbial 1494:1502 arg1 subpopulations 1504:1517 the microbial subpopulations 1490:1517 the microbial subpopulations 1490:1517 Interestingly, the community requires cross-feeding for producing a realistic set of short-chain fatty acids from an input of glucose, If we let the composition of the microbial subpopulations change during invasion of adjacent space, a complex and stratified microbiota evolves, with subspecies specializing on cross-feeding interactions via a mechanism of compensated trait loss. 28511646 2 11 theme inflammatory 601:612 arg1 disease 620:626 inflammatory bowel disease 601:626 inflammatory bowel disease 601:626 Together, these microbial species form a complex food web that can break down nutrient sources that our own digestive enzymes cannot handle, including complex polysaccharides, producing short chain fatty acids and additional metabolites, e.g., vitamin K. Microbial diversity is important for colonic health: Changes in the composition of the microbiota have been associated with inflammatory bowel disease, diabetes, obesity and Crohn's disease, and make the microbiota more vulnerable to infestation by harmful species, e.g., Clostridium difficile. 28511646 2 12 dep difficile 761:769 arg1 e.g. 743:746 e.g. 743:746 e.g. 743:746 Together, these microbial species form a complex food web that can break down nutrient sources that our own digestive enzymes cannot handle, including complex polysaccharides, producing short chain fatty acids and additional metabolites, e.g., vitamin K. Microbial diversity is important for colonic health: Changes in the composition of the microbiota have been associated with inflammatory bowel disease, diabetes, obesity and Crohn's disease, and make the microbiota more vulnerable to infestation by harmful species, e.g., Clostridium difficile. 28511646 4 13 theme populations 1088:1098 arg1 GEM 1070:1072 GEM 1070:1072 GEM 1070:1072 The model features genome-scale metabolic models (GEM) of microbial populations, resource sharing via extracellular metabolites, and spatial population dynamics and evolution. 28511646 4 13 theme populations 1088:1098 arg1 models 1062:1067 genome-scale metabolic models 1039:1067 genome-scale metabolic models (GEM) of microbial populations, resource sharing via extracellular metabolites, and spatial population dynamics and evolution 1039:1193 The model features genome-scale metabolic models (GEM) of microbial populations, resource sharing via extracellular metabolites, and spatial population dynamics and evolution. 28511646 2 14 theme down 295:298 arg1 sources 309:315 down nutrient sources 295:315 down nutrient sources 295:315 Together, these microbial species form a complex food web that can break down nutrient sources that our own digestive enzymes cannot handle, including complex polysaccharides, producing short chain fatty acids and additional metabolites, e.g., vitamin K. Microbial diversity is important for colonic health: Changes in the composition of the microbiota have been associated with inflammatory bowel disease, diabetes, obesity and Crohn's disease, and make the microbiota more vulnerable to infestation by harmful species, e.g., Clostridium difficile. 28511646 3 15 theme spatial 981:987 arg1 environment 1007:1017 a spatial gut-like, tubular environment 979:1017 a spatial gut-like, tubular environment 979:1017 To get a grip on the controlling factors of microbial diversity in the gut, we here propose a multi-scale, spatiotemporal dynamic flux-balance analysis model to study the emergence of metabolic diversity in a spatial gut-like, tubular environment. 28511646 8 16 from factors 1943:1949 arg1 gut 1981:1983 the gut 1977:1983 the gut 1977:1983 CONCLUSIONS In conclusion, this in silico model is a helpful tool in systems biology to predict and explain the controlling factors of microbial diversity in the gut. 28511646 8 17 theme systems 1888:1894 arg1 biology 1896:1902 systems biology 1888:1902 systems biology 1888:1902 CONCLUSIONS In conclusion, this in silico model is a helpful tool in systems biology to predict and explain the controlling factors of microbial diversity in the gut. 28511646 6 18 theme short-chain 1411:1421 arg1 acids 1429:1433 short-chain fatty acids 1411:1433 short-chain fatty acids 1411:1433 Interestingly, the community requires cross-feeding for producing a realistic set of short-chain fatty acids from an input of glucose, If we let the composition of the microbial subpopulations change during invasion of adjacent space, a complex and stratified microbiota evolves, with subspecies specializing on cross-feeding interactions via a mechanism of compensated trait loss. 28511646 6 19 theme complex 1563:1569 arg1 microbiota 1586:1595 a complex and stratified microbiota 1561:1595 a complex and stratified microbiota 1561:1595 Interestingly, the community requires cross-feeding for producing a realistic set of short-chain fatty acids from an input of glucose, If we let the composition of the microbial subpopulations change during invasion of adjacent space, a complex and stratified microbiota evolves, with subspecies specializing on cross-feeding interactions via a mechanism of compensated trait loss. 28511646 1 20 theme species 213:219 arg1 hundreds 191:198 hundreds 191:198 hundreds of different species 191:219 BACKGROUND The human gut contains approximately 1014 bacteria, belonging to hundreds of different species. 28511646 5 21 dep RESULTS 1196:1202 arg1 emerge 1246:1251 emerge 1246:1251 emerge 1246:1251 RESULTS In this model, cross-feeding interactions emerge readily, despite the species' ability to metabolize sugars autonomously. 28511646 6 22 theme adjacent 1545:1552 arg1 space 1554:1558 adjacent space 1545:1558 adjacent space 1545:1558 Interestingly, the community requires cross-feeding for producing a realistic set of short-chain fatty acids from an input of glucose, If we let the composition of the microbial subpopulations change during invasion of adjacent space, a complex and stratified microbiota evolves, with subspecies specializing on cross-feeding interactions via a mechanism of compensated trait loss. 28511646 1 23 theme human 130:134 arg1 gut 136:138 The human gut 126:138 The human gut 126:138 BACKGROUND The human gut contains approximately 1014 bacteria, belonging to hundreds of different species. 28511646 7 24 theme microbial 1712:1720 arg1 diversity 1722:1730 microbial diversity 1712:1730 microbial diversity 1712:1730 The microbial diversity and stratification collapse if the flux through the gut is enhanced to mimic diarrhea. 28511646 4 25 theme resource 1101:1108 arg1 GEM 1070:1072 GEM 1070:1072 GEM 1070:1072 The model features genome-scale metabolic models (GEM) of microbial populations, resource sharing via extracellular metabolites, and spatial population dynamics and evolution. 28511646 4 25 theme resource 1101:1108 arg1 models 1062:1067 genome-scale metabolic models 1039:1067 genome-scale metabolic models (GEM) of microbial populations, resource sharing via extracellular metabolites, and spatial population dynamics and evolution 1039:1193 The model features genome-scale metabolic models (GEM) of microbial populations, resource sharing via extracellular metabolites, and spatial population dynamics and evolution. 28511646 3 26 theme microbial 816:824 arg1 diversity 826:834 microbial diversity 816:834 microbial diversity in the gut 816:845 To get a grip on the controlling factors of microbial diversity in the gut, we here propose a multi-scale, spatiotemporal dynamic flux-balance analysis model to study the emergence of metabolic diversity in a spatial gut-like, tubular environment. 28511646 0 27 theme microbial 13:21 arg1 diversity 23:31 microbial diversity 13:31 microbial diversity 13:31 Emergence of microbial diversity due to cross-feeding interactions in a spatial model of gut microbial metabolism. 28511646 0 28 theme spatial 72:78 arg1 model 80:84 a spatial model 70:84 a spatial model of gut microbial metabolism 70:112 Emergence of microbial diversity due to cross-feeding interactions in a spatial model of gut microbial metabolism. 28511646 3 29 theme diversity 826:834 arg1 factors 805:811 the controlling factors 789:811 the controlling factors of microbial diversity in the gut 789:845 To get a grip on the controlling factors of microbial diversity in the gut, we here propose a multi-scale, spatiotemporal dynamic flux-balance analysis model to study the emergence of metabolic diversity in a spatial gut-like, tubular environment. 28511646 2 30 theme colonic 514:520 arg1 health 522:527 colonic health 514:527 colonic health 514:527 Together, these microbial species form a complex food web that can break down nutrient sources that our own digestive enzymes cannot handle, including complex polysaccharides, producing short chain fatty acids and additional metabolites, e.g., vitamin K. Microbial diversity is important for colonic health: Changes in the composition of the microbiota have been associated with inflammatory bowel disease, diabetes, obesity and Crohn's disease, and make the microbiota more vulnerable to infestation by harmful species, e.g., Clostridium difficile. 28511646 7 31 dep diversity 1722:1730 arg1 The 1708:1710 The 1708:1710 The 1708:1710 The microbial diversity and stratification collapse if the flux through the gut is enhanced to mimic diarrhea. 28511646 8 32 theme microbial 1954:1962 arg1 diversity 1964:1972 microbial diversity 1954:1972 microbial diversity 1954:1972 CONCLUSIONS In conclusion, this in silico model is a helpful tool in systems biology to predict and explain the controlling factors of microbial diversity in the gut. 28511646 3 33 theme controlling 793:803 arg1 factors 805:811 the controlling factors 789:811 the controlling factors of microbial diversity in the gut 789:845 To get a grip on the controlling factors of microbial diversity in the gut, we here propose a multi-scale, spatiotemporal dynamic flux-balance analysis model to study the emergence of metabolic diversity in a spatial gut-like, tubular environment. 28511646 0 34 theme microbial 93:101 arg1 metabolism 103:112 gut microbial metabolism 89:112 gut microbial metabolism 89:112 Emergence of microbial diversity due to cross-feeding interactions in a spatial model of gut microbial metabolism. 28511646 2 35 theme additional 436:445 arg1 metabolites 447:457 additional metabolites 436:457 additional metabolites 436:457 Together, these microbial species form a complex food web that can break down nutrient sources that our own digestive enzymes cannot handle, including complex polysaccharides, producing short chain fatty acids and additional metabolites, e.g., vitamin K. Microbial diversity is important for colonic health: Changes in the composition of the microbiota have been associated with inflammatory bowel disease, diabetes, obesity and Crohn's disease, and make the microbiota more vulnerable to infestation by harmful species, e.g., Clostridium difficile. 28511646 6 36 theme trait 1696:1700 arg1 loss 1702:1705 compensated trait loss 1684:1705 compensated trait loss 1684:1705 Interestingly, the community requires cross-feeding for producing a realistic set of short-chain fatty acids from an input of glucose, If we let the composition of the microbial subpopulations change during invasion of adjacent space, a complex and stratified microbiota evolves, with subspecies specializing on cross-feeding interactions via a mechanism of compensated trait loss. 28511646 4 37 theme population 1161:1170 arg1 dynamics 1172:1179 spatial population dynamics 1153:1179 spatial population dynamics 1153:1179 The model features genome-scale metabolic models (GEM) of microbial populations, resource sharing via extracellular metabolites, and spatial population dynamics and evolution. 28511646 6 38 theme fatty 1423:1427 arg1 acids 1429:1433 short-chain fatty acids 1411:1433 short-chain fatty acids 1411:1433 Interestingly, the community requires cross-feeding for producing a realistic set of short-chain fatty acids from an input of glucose, If we let the composition of the microbial subpopulations change during invasion of adjacent space, a complex and stratified microbiota evolves, with subspecies specializing on cross-feeding interactions via a mechanism of compensated trait loss. 28511646 6 39 theme stratified 1575:1584 arg1 microbiota 1586:1595 a complex and stratified microbiota 1561:1595 a complex and stratified microbiota 1561:1595 Interestingly, the community requires cross-feeding for producing a realistic set of short-chain fatty acids from an input of glucose, If we let the composition of the microbial subpopulations change during invasion of adjacent space, a complex and stratified microbiota evolves, with subspecies specializing on cross-feeding interactions via a mechanism of compensated trait loss. 28511646 3 40 from emergence 943:951 arg1 environment 1007:1017 a spatial gut-like, tubular environment 979:1017 a spatial gut-like, tubular environment 979:1017 To get a grip on the controlling factors of microbial diversity in the gut, we here propose a multi-scale, spatiotemporal dynamic flux-balance analysis model to study the emergence of metabolic diversity in a spatial gut-like, tubular environment. 28511646 2 41 theme chain 414:418 arg1 acids 426:430 short chain fatty acids 408:430 short chain fatty acids 408:430 Together, these microbial species form a complex food web that can break down nutrient sources that our own digestive enzymes cannot handle, including complex polysaccharides, producing short chain fatty acids and additional metabolites, e.g., vitamin K. Microbial diversity is important for colonic health: Changes in the composition of the microbiota have been associated with inflammatory bowel disease, diabetes, obesity and Crohn's disease, and make the microbiota more vulnerable to infestation by harmful species, e.g., Clostridium difficile. 28511646 2 42 theme vulnerable 697:706 arg1 microbiota 681:690 the microbiota 677:690 the microbiota more vulnerable 677:706 Together, these microbial species form a complex food web that can break down nutrient sources that our own digestive enzymes cannot handle, including complex polysaccharides, producing short chain fatty acids and additional metabolites, e.g., vitamin K. Microbial diversity is important for colonic health: Changes in the composition of the microbiota have been associated with inflammatory bowel disease, diabetes, obesity and Crohn's disease, and make the microbiota more vulnerable to infestation by harmful species, e.g., Clostridium difficile. 28511646 6 43 theme realistic 1394:1402 arg1 set 1404:1406 a realistic set 1392:1406 a realistic set of short-chain fatty acids 1392:1433 Interestingly, the community requires cross-feeding for producing a realistic set of short-chain fatty acids from an input of glucose, If we let the composition of the microbial subpopulations change during invasion of adjacent space, a complex and stratified microbiota evolves, with subspecies specializing on cross-feeding interactions via a mechanism of compensated trait loss. 28511646 6 43 theme realistic 1394:1402 arg1 acids 1429:1433 short-chain fatty acids 1411:1433 short-chain fatty acids 1411:1433 Interestingly, the community requires cross-feeding for producing a realistic set of short-chain fatty acids from an input of glucose, If we let the composition of the microbial subpopulations change during invasion of adjacent space, a complex and stratified microbiota evolves, with subspecies specializing on cross-feeding interactions via a mechanism of compensated trait loss. 28511646 3 44 theme analysis 915:922 arg1 model 924:928 a multi-scale, spatiotemporal dynamic flux-balance analysis model 864:928 model 924:928 To get a grip on the controlling factors of microbial diversity in the gut, we here propose a multi-scale, spatiotemporal dynamic flux-balance analysis model to study the emergence of metabolic diversity in a spatial gut-like, tubular environment. 28511646 9 45 theme complex 2023:2029 arg1 sources 2040:2046 complex nutrient sources 2023:2046 complex nutrient sources 2023:2046 It can be extended to include, e.g., complex nutrient sources, and host-microbiota interactions via the intestinal wall. 28511646 2 46 theme own 326:328 arg1 enzymes 340:346 our own digestive enzymes 322:346 our own digestive enzymes 322:346 Together, these microbial species form a complex food web that can break down nutrient sources that our own digestive enzymes cannot handle, including complex polysaccharides, producing short chain fatty acids and additional metabolites, e.g., vitamin K. Microbial diversity is important for colonic health: Changes in the composition of the microbiota have been associated with inflammatory bowel disease, diabetes, obesity and Crohn's disease, and make the microbiota more vulnerable to infestation by harmful species, e.g., Clostridium difficile. 28511646 0 47 theme cross-feeding 40:52 arg1 interactions 54:65 cross-feeding interactions 40:65 cross-feeding interactions 40:65 Emergence of microbial diversity due to cross-feeding interactions in a spatial model of gut microbial metabolism. 28511646 3 48 theme dynamic 894:900 arg1 model 924:928 a multi-scale, spatiotemporal dynamic flux-balance analysis model 864:928 model 924:928 To get a grip on the controlling factors of microbial diversity in the gut, we here propose a multi-scale, spatiotemporal dynamic flux-balance analysis model to study the emergence of metabolic diversity in a spatial gut-like, tubular environment. 28511646 2 49 theme microbial 238:246 arg1 species 248:254 these microbial species 232:254 these microbial species 232:254 Together, these microbial species form a complex food web that can break down nutrient sources that our own digestive enzymes cannot handle, including complex polysaccharides, producing short chain fatty acids and additional metabolites, e.g., vitamin K. Microbial diversity is important for colonic health: Changes in the composition of the microbiota have been associated with inflammatory bowel disease, diabetes, obesity and Crohn's disease, and make the microbiota more vulnerable to infestation by harmful species, e.g., Clostridium difficile. 28511646 4 50 theme metabolic 1052:1060 arg1 GEM 1070:1072 GEM 1070:1072 GEM 1070:1072 The model features genome-scale metabolic models (GEM) of microbial populations, resource sharing via extracellular metabolites, and spatial population dynamics and evolution. 28511646 4 50 theme metabolic 1052:1060 arg1 models 1062:1067 genome-scale metabolic models 1039:1067 genome-scale metabolic models (GEM) of microbial populations, resource sharing via extracellular metabolites, and spatial population dynamics and evolution 1039:1193 The model features genome-scale metabolic models (GEM) of microbial populations, resource sharing via extracellular metabolites, and spatial population dynamics and evolution. 28511646 6 51 theme glucose 1452:1458 arg1 input 1443:1447 an input 1440:1447 an input of glucose 1440:1458 Interestingly, the community requires cross-feeding for producing a realistic set of short-chain fatty acids from an input of glucose, If we let the composition of the microbial subpopulations change during invasion of adjacent space, a complex and stratified microbiota evolves, with subspecies specializing on cross-feeding interactions via a mechanism of compensated trait loss. 28511646 2 52 from Changes 530:536 arg1 composition 545:555 the composition 541:555 the composition of the microbiota 541:573 Together, these microbial species form a complex food web that can break down nutrient sources that our own digestive enzymes cannot handle, including complex polysaccharides, producing short chain fatty acids and additional metabolites, e.g., vitamin K. Microbial diversity is important for colonic health: Changes in the composition of the microbiota have been associated with inflammatory bowel disease, diabetes, obesity and Crohn's disease, and make the microbiota more vulnerable to infestation by harmful species, e.g., Clostridium difficile. 28511646 3 53 theme diversity 966:974 arg1 emergence 943:951 the emergence 939:951 the emergence of metabolic diversity in a spatial gut-like, tubular environment 939:1017 To get a grip on the controlling factors of microbial diversity in the gut, we here propose a multi-scale, spatiotemporal dynamic flux-balance analysis model to study the emergence of metabolic diversity in a spatial gut-like, tubular environment. 28511646 2 54 theme microbiota 564:573 arg1 composition 545:555 the composition 541:555 the composition of the microbiota 541:573 Together, these microbial species form a complex food web that can break down nutrient sources that our own digestive enzymes cannot handle, including complex polysaccharides, producing short chain fatty acids and additional metabolites, e.g., vitamin K. Microbial diversity is important for colonic health: Changes in the composition of the microbiota have been associated with inflammatory bowel disease, diabetes, obesity and Crohn's disease, and make the microbiota more vulnerable to infestation by harmful species, e.g., Clostridium difficile. 28511646 4 55 theme microbial 1078:1086 arg1 populations 1088:1098 microbial populations 1078:1098 microbial populations 1078:1098 The model features genome-scale metabolic models (GEM) of microbial populations, resource sharing via extracellular metabolites, and spatial population dynamics and evolution. 28511646 2 56 theme food 271:274 arg1 web 276:278 a complex food web 261:278 a complex food web that can break down nutrient sources that our own digestive enzymes cannot handle, including complex polysaccharides, producing short chain fatty acids and additional metabolites, e.g., vitamin K. Microbial diversity is important for colonic health: Changes in the composition of the microbiota have been associated with inflammatory bowel disease, diabetes, obesity and Crohn's disease, and make the microbiota more vulnerable to infestation by harmful species, e.g., Clostridium difficile 261:769 Together, these microbial species form a complex food web that can break down nutrient sources that our own digestive enzymes cannot handle, including complex polysaccharides, producing short chain fatty acids and additional metabolites, e.g., vitamin K. Microbial diversity is important for colonic health: Changes in the composition of the microbiota have been associated with inflammatory bowel disease, diabetes, obesity and Crohn's disease, and make the microbiota more vulnerable to infestation by harmful species, e.g., Clostridium difficile. 28511646 6 57 theme subpopulations 1504:1517 arg1 composition 1475:1485 the composition 1471:1485 the composition of the microbial subpopulations 1471:1517 Interestingly, the community requires cross-feeding for producing a realistic set of short-chain fatty acids from an input of glucose, If we let the composition of the microbial subpopulations change during invasion of adjacent space, a complex and stratified microbiota evolves, with subspecies specializing on cross-feeding interactions via a mechanism of compensated trait loss. 28511646 2 58 theme bowel 614:618 arg1 disease 620:626 inflammatory bowel disease 601:626 inflammatory bowel disease 601:626 Together, these microbial species form a complex food web that can break down nutrient sources that our own digestive enzymes cannot handle, including complex polysaccharides, producing short chain fatty acids and additional metabolites, e.g., vitamin K. Microbial diversity is important for colonic health: Changes in the composition of the microbiota have been associated with inflammatory bowel disease, diabetes, obesity and Crohn's disease, and make the microbiota more vulnerable to infestation by harmful species, e.g., Clostridium difficile. 28511646 3 59 theme gut-like 989:996 arg1 environment 1007:1017 a spatial gut-like, tubular environment 979:1017 a spatial gut-like, tubular environment 979:1017 To get a grip on the controlling factors of microbial diversity in the gut, we here propose a multi-scale, spatiotemporal dynamic flux-balance analysis model to study the emergence of metabolic diversity in a spatial gut-like, tubular environment. 28511646 3 60 from gut 843:845 arg1 factors 805:811 the controlling factors 789:811 the controlling factors of microbial diversity in the gut 789:845 To get a grip on the controlling factors of microbial diversity in the gut, we here propose a multi-scale, spatiotemporal dynamic flux-balance analysis model to study the emergence of metabolic diversity in a spatial gut-like, tubular environment. 28511646 8 61 dep CONCLUSIONS 1819:1829 arg1 tool 1880:1883 a helpful tool 1870:1883 a helpful tool in systems biology to predict and explain the controlling factors of microbial diversity in the gut 1870:1983 CONCLUSIONS In conclusion, this in silico model is a helpful tool in systems biology to predict and explain the controlling factors of microbial diversity in the gut. 28511646 8 61 dep CONCLUSIONS 1819:1829 arg1 model 1861:1865 this in silico model 1846:1865 this in silico model 1846:1865 CONCLUSIONS In conclusion, this in silico model is a helpful tool in systems biology to predict and explain the controlling factors of microbial diversity in the gut. 28511646 8 62 theme helpful 1872:1878 arg1 tool 1880:1883 a helpful tool 1870:1883 a helpful tool in systems biology to predict and explain the controlling factors of microbial diversity in the gut 1870:1983 CONCLUSIONS In conclusion, this in silico model is a helpful tool in systems biology to predict and explain the controlling factors of microbial diversity in the gut. 28511646 8 62 theme helpful 1872:1878 arg1 model 1861:1865 this in silico model 1846:1865 this in silico model 1846:1865 CONCLUSIONS In conclusion, this in silico model is a helpful tool in systems biology to predict and explain the controlling factors of microbial diversity in the gut. 28511646 2 63 theme nutrient 300:307 arg1 sources 309:315 down nutrient sources 295:315 down nutrient sources 295:315 Together, these microbial species form a complex food web that can break down nutrient sources that our own digestive enzymes cannot handle, including complex polysaccharides, producing short chain fatty acids and additional metabolites, e.g., vitamin K. Microbial diversity is important for colonic health: Changes in the composition of the microbiota have been associated with inflammatory bowel disease, diabetes, obesity and Crohn's disease, and make the microbiota more vulnerable to infestation by harmful species, e.g., Clostridium difficile. 28511646 3 64 from factors 805:811 arg1 gut 843:845 the gut 839:845 the gut 839:845 To get a grip on the controlling factors of microbial diversity in the gut, we here propose a multi-scale, spatiotemporal dynamic flux-balance analysis model to study the emergence of metabolic diversity in a spatial gut-like, tubular environment. 28511646 2 65 theme Clostridium 749:759 arg1 difficile 761:769 Clostridium difficile 749:769 Clostridium difficile 749:769 Together, these microbial species form a complex food web that can break down nutrient sources that our own digestive enzymes cannot handle, including complex polysaccharides, producing short chain fatty acids and additional metabolites, e.g., vitamin K. Microbial diversity is important for colonic health: Changes in the composition of the microbiota have been associated with inflammatory bowel disease, diabetes, obesity and Crohn's disease, and make the microbiota more vulnerable to infestation by harmful species, e.g., Clostridium difficile. 28511646 6 66 theme compensated 1684:1694 arg1 loss 1702:1705 compensated trait loss 1684:1705 compensated trait loss 1684:1705 Interestingly, the community requires cross-feeding for producing a realistic set of short-chain fatty acids from an input of glucose, If we let the composition of the microbial subpopulations change during invasion of adjacent space, a complex and stratified microbiota evolves, with subspecies specializing on cross-feeding interactions via a mechanism of compensated trait loss. 28511646 1 67 theme different 203:211 arg1 species 213:219 different species 203:219 different species 203:219 BACKGROUND The human gut contains approximately 1014 bacteria, belonging to hundreds of different species. 28511646 0 68 theme gut 89:91 arg1 metabolism 103:112 gut microbial metabolism 89:112 gut microbial metabolism 89:112 Emergence of microbial diversity due to cross-feeding interactions in a spatial model of gut microbial metabolism. 28511646 4 69 theme spatial 1153:1159 arg1 dynamics 1172:1179 spatial population dynamics 1153:1179 spatial population dynamics 1153:1179 The model features genome-scale metabolic models (GEM) of microbial populations, resource sharing via extracellular metabolites, and spatial population dynamics and evolution. 28511646 6 70 theme space 1554:1558 arg1 invasion 1533:1540 invasion 1533:1540 invasion of adjacent space 1533:1558 Interestingly, the community requires cross-feeding for producing a realistic set of short-chain fatty acids from an input of glucose, If we let the composition of the microbial subpopulations change during invasion of adjacent space, a complex and stratified microbiota evolves, with subspecies specializing on cross-feeding interactions via a mechanism of compensated trait loss. 28511646 7 71 theme stratification 1736:1749 arg1 collapse 1751:1758 stratification collapse 1736:1758 stratification collapse 1736:1758 The microbial diversity and stratification collapse if the flux through the gut is enhanced to mimic diarrhea. 28511646 6 72 theme cross-feeding 1638:1650 arg1 interactions 1652:1663 cross-feeding interactions 1638:1663 cross-feeding interactions 1638:1663 Interestingly, the community requires cross-feeding for producing a realistic set of short-chain fatty acids from an input of glucose, If we let the composition of the microbial subpopulations change during invasion of adjacent space, a complex and stratified microbiota evolves, with subspecies specializing on cross-feeding interactions via a mechanism of compensated trait loss. 28511646 8 73 theme controlling 1931:1941 arg1 factors 1943:1949 the controlling factors 1927:1949 the controlling factors of microbial diversity in the gut 1927:1983 CONCLUSIONS In conclusion, this in silico model is a helpful tool in systems biology to predict and explain the controlling factors of microbial diversity in the gut. 28511646 2 74 theme Microbial 477:485 arg1 diversity 487:495 Microbial diversity 477:495 Microbial diversity 477:495 Together, these microbial species form a complex food web that can break down nutrient sources that our own digestive enzymes cannot handle, including complex polysaccharides, producing short chain fatty acids and additional metabolites, e.g., vitamin K. Microbial diversity is important for colonic health: Changes in the composition of the microbiota have been associated with inflammatory bowel disease, diabetes, obesity and Crohn's disease, and make the microbiota more vulnerable to infestation by harmful species, e.g., Clostridium difficile. 28511646 4 75 theme extracellular 1122:1134 arg1 metabolites 1136:1146 extracellular metabolites 1122:1146 extracellular metabolites 1122:1146 The model features genome-scale metabolic models (GEM) of microbial populations, resource sharing via extracellular metabolites, and spatial population dynamics and evolution. 28511646 5 76 theme cross-feeding 1219:1231 arg1 interactions 1233:1244 cross-feeding interactions 1219:1244 cross-feeding interactions 1219:1244 RESULTS In this model, cross-feeding interactions emerge readily, despite the species' ability to metabolize sugars autonomously. 28511646 0 77 from model 80:84 arg1 due 33:35 due 33:35 due 33:35 Emergence of microbial diversity due to cross-feeding interactions in a spatial model of gut microbial metabolism. 28511646 8 78 theme diversity 1964:1972 arg1 factors 1943:1949 the controlling factors 1927:1949 the controlling factors of microbial diversity in the gut 1927:1983 CONCLUSIONS In conclusion, this in silico model is a helpful tool in systems biology to predict and explain the controlling factors of microbial diversity in the gut. 28511646 8 79 dep in 1851:1852 arg1 silico 1854:1859 silico 1854:1859 silico 1854:1859 CONCLUSIONS In conclusion, this in silico model is a helpful tool in systems biology to predict and explain the controlling factors of microbial diversity in the gut. 28511646 0 80 theme metabolism 103:112 arg1 model 80:84 a spatial model 70:84 a spatial model of gut microbial metabolism 70:112 Emergence of microbial diversity due to cross-feeding interactions in a spatial model of gut microbial metabolism. 28511646 6 81 theme loss 1702:1705 arg1 mechanism 1671:1679 a mechanism 1669:1679 a mechanism of compensated trait loss 1669:1705 Interestingly, the community requires cross-feeding for producing a realistic set of short-chain fatty acids from an input of glucose, If we let the composition of the microbial subpopulations change during invasion of adjacent space, a complex and stratified microbiota evolves, with subspecies specializing on cross-feeding interactions via a mechanism of compensated trait loss. 28511646 4 82 theme dynamics 1172:1179 arg1 GEM 1070:1072 GEM 1070:1072 GEM 1070:1072 The model features genome-scale metabolic models (GEM) of microbial populations, resource sharing via extracellular metabolites, and spatial population dynamics and evolution. 28511646 4 82 theme dynamics 1172:1179 arg1 models 1062:1067 genome-scale metabolic models 1039:1067 genome-scale metabolic models (GEM) of microbial populations, resource sharing via extracellular metabolites, and spatial population dynamics and evolution 1039:1193 The model features genome-scale metabolic models (GEM) of microbial populations, resource sharing via extracellular metabolites, and spatial population dynamics and evolution. 28511646 1 83 dep BACKGROUND 115:124 arg1 contains 140:147 contains 140:147 contains approximately 1014 bacteria, belonging to hundreds of different species 140:219 BACKGROUND The human gut contains approximately 1014 bacteria, belonging to hundreds of different species. 28511646 2 84 theme complex 373:379 arg1 polysaccharides 381:395 complex polysaccharides 373:395 complex polysaccharides 373:395 Together, these microbial species form a complex food web that can break down nutrient sources that our own digestive enzymes cannot handle, including complex polysaccharides, producing short chain fatty acids and additional metabolites, e.g., vitamin K. Microbial diversity is important for colonic health: Changes in the composition of the microbiota have been associated with inflammatory bowel disease, diabetes, obesity and Crohn's disease, and make the microbiota more vulnerable to infestation by harmful species, e.g., Clostridium difficile. 28511646 6 85 theme acids 1429:1433 arg1 set 1404:1406 a realistic set 1392:1406 a realistic set of short-chain fatty acids 1392:1433 Interestingly, the community requires cross-feeding for producing a realistic set of short-chain fatty acids from an input of glucose, If we let the composition of the microbial subpopulations change during invasion of adjacent space, a complex and stratified microbiota evolves, with subspecies specializing on cross-feeding interactions via a mechanism of compensated trait loss. 28511646 6 85 theme acids 1429:1433 arg1 acids 1429:1433 short-chain fatty acids 1411:1433 short-chain fatty acids 1411:1433 Interestingly, the community requires cross-feeding for producing a realistic set of short-chain fatty acids from an input of glucose, If we let the composition of the microbial subpopulations change during invasion of adjacent space, a complex and stratified microbiota evolves, with subspecies specializing on cross-feeding interactions via a mechanism of compensated trait loss. 28511646 0 86 theme diversity 23:31 arg1 Emergence 0:8 Emergence 0:8 Emergence of microbial diversity 0:31 Emergence of microbial diversity due to cross-feeding interactions in a spatial model of gut microbial metabolism. 28511646 3 87 theme spatiotemporal 879:892 arg1 model 924:928 a multi-scale, spatiotemporal dynamic flux-balance analysis model 864:928 model 924:928 To get a grip on the controlling factors of microbial diversity in the gut, we here propose a multi-scale, spatiotemporal dynamic flux-balance analysis model to study the emergence of metabolic diversity in a spatial gut-like, tubular environment. 28511646 2 88 theme fatty 420:424 arg1 acids 426:430 short chain fatty acids 408:430 short chain fatty acids 408:430 Together, these microbial species form a complex food web that can break down nutrient sources that our own digestive enzymes cannot handle, including complex polysaccharides, producing short chain fatty acids and additional metabolites, e.g., vitamin K. Microbial diversity is important for colonic health: Changes in the composition of the microbiota have been associated with inflammatory bowel disease, diabetes, obesity and Crohn's disease, and make the microbiota more vulnerable to infestation by harmful species, e.g., Clostridium difficile. 28511646 3 89 from grip 781:784 arg1 factors 805:811 the controlling factors 789:811 the controlling factors of microbial diversity in the gut 789:845 To get a grip on the controlling factors of microbial diversity in the gut, we here propose a multi-scale, spatiotemporal dynamic flux-balance analysis model to study the emergence of metabolic diversity in a spatial gut-like, tubular environment. 28511646 2 90 theme short 408:412 arg1 acids 426:430 short chain fatty acids 408:430 short chain fatty acids 408:430 Together, these microbial species form a complex food web that can break down nutrient sources that our own digestive enzymes cannot handle, including complex polysaccharides, producing short chain fatty acids and additional metabolites, e.g., vitamin K. Microbial diversity is important for colonic health: Changes in the composition of the microbiota have been associated with inflammatory bowel disease, diabetes, obesity and Crohn's disease, and make the microbiota more vulnerable to infestation by harmful species, e.g., Clostridium difficile. 28511646 3 91 theme multi-scale 866:876 arg1 model 924:928 a multi-scale, spatiotemporal dynamic flux-balance analysis model 864:928 model 924:928 To get a grip on the controlling factors of microbial diversity in the gut, we here propose a multi-scale, spatiotemporal dynamic flux-balance analysis model to study the emergence of metabolic diversity in a spatial gut-like, tubular environment. 28511646 2 92 dep K. 474:475 arg1 important 500:508 important 500:508 important 500:508 Together, these microbial species form a complex food web that can break down nutrient sources that our own digestive enzymes cannot handle, including complex polysaccharides, producing short chain fatty acids and additional metabolites, e.g., vitamin K. Microbial diversity is important for colonic health: Changes in the composition of the microbiota have been associated with inflammatory bowel disease, diabetes, obesity and Crohn's disease, and make the microbiota more vulnerable to infestation by harmful species, e.g., Clostridium difficile. 28511646 2 92 dep K. 474:475 arg1 e.g. 460:463 e.g. 460:463 e.g. 460:463 Together, these microbial species form a complex food web that can break down nutrient sources that our own digestive enzymes cannot handle, including complex polysaccharides, producing short chain fatty acids and additional metabolites, e.g., vitamin K. Microbial diversity is important for colonic health: Changes in the composition of the microbiota have been associated with inflammatory bowel disease, diabetes, obesity and Crohn's disease, and make the microbiota more vulnerable to infestation by harmful species, e.g., Clostridium difficile. 28511646 9 93 theme nutrient 2031:2038 arg1 sources 2040:2046 complex nutrient sources 2023:2046 complex nutrient sources 2023:2046 It can be extended to include, e.g., complex nutrient sources, and host-microbiota interactions via the intestinal wall. 28511646 3 94 theme flux-balance 902:913 arg1 model 924:928 a multi-scale, spatiotemporal dynamic flux-balance analysis model 864:928 model 924:928 To get a grip on the controlling factors of microbial diversity in the gut, we here propose a multi-scale, spatiotemporal dynamic flux-balance analysis model to study the emergence of metabolic diversity in a spatial gut-like, tubular environment. 28511646 4 95 theme genome-scale 1039:1050 arg1 GEM 1070:1072 GEM 1070:1072 GEM 1070:1072 The model features genome-scale metabolic models (GEM) of microbial populations, resource sharing via extracellular metabolites, and spatial population dynamics and evolution. 28511646 4 95 theme genome-scale 1039:1050 arg1 models 1062:1067 genome-scale metabolic models 1039:1067 genome-scale metabolic models (GEM) of microbial populations, resource sharing via extracellular metabolites, and spatial population dynamics and evolution 1039:1193 The model features genome-scale metabolic models (GEM) of microbial populations, resource sharing via extracellular metabolites, and spatial population dynamics and evolution. 28511646 9 96 theme host-microbiota 2053:2067 arg1 interactions 2069:2080 host-microbiota interactions 2053:2080 host-microbiota interactions 2053:2080 It can be extended to include, e.g., complex nutrient sources, and host-microbiota interactions via the intestinal wall. 28511646 8 97 from tool 1880:1883 arg1 biology 1896:1902 systems biology 1888:1902 systems biology 1888:1902 CONCLUSIONS In conclusion, this in silico model is a helpful tool in systems biology to predict and explain the controlling factors of microbial diversity in the gut. 28511646 8 97 from tool 1880:1883 arg1 conclusion 1834:1843 conclusion 1834:1843 conclusion 1834:1843 CONCLUSIONS In conclusion, this in silico model is a helpful tool in systems biology to predict and explain the controlling factors of microbial diversity in the gut. 27115614 6 0 theme living 926:931 arg1 tissues 933:939 living tissues 926:939 living tissues of desert-growing A. sphaerocephala 926:975 To maximize the representation of conditional transcripts, mRNA was obtained from 17 samples, including living tissues of desert-growing A. sphaerocephala, seeds germinated in the laboratory, and calli subjected to no stress (control) and high and low temperature, high and low osmotic, and salt stresses. 27115614 10 1 theme traits 1690:1695 arg1 dissection 1662:1671 functional dissection 1651:1671 functional dissection of the important traits of A. sphaerocephala 1651:1716 CONCLUSION The present work provides abundant genomic information for functional dissection of the important traits of A. sphaerocephala and contributes to the current understanding of molecular adaptive mechanisms of A. sphaerocephala in the desert environment. 27115614 11 2 theme crops 2109:2113 arg1 composition 2090:2100 the fatty acid composition 2075:2100 the fatty acid composition of oil crops 2075:2113 Identification of the key genes in the unsaturated fatty acid synthesis pathway could increase understanding of the biological regulatory mechanisms of fatty acid composition traits in plants and facilitate genetic manipulation of the fatty acid composition of oil crops. 27115614 10 3 dep CONCLUSION 1581:1590 arg1 provides 1609:1616 provides 1609:1616 provides abundant genomic information for functional dissection of the important traits of A. sphaerocephala 1609:1716 CONCLUSION The present work provides abundant genomic information for functional dissection of the important traits of A. sphaerocephala and contributes to the current understanding of molecular adaptive mechanisms of A. sphaerocephala in the desert environment. 27115614 10 3 dep CONCLUSION 1581:1590 arg1 contributes 1722:1732 contributes 1722:1732 contributes to the current understanding of molecular adaptive mechanisms of A. sphaerocephala in the desert environment 1722:1841 CONCLUSION The present work provides abundant genomic information for functional dissection of the important traits of A. sphaerocephala and contributes to the current understanding of molecular adaptive mechanisms of A. sphaerocephala in the desert environment. 27115614 3 4 theme bio-energy 542:551 arg1 source 532:537 a potential valuable source 511:537 a potential valuable source of bio-energy 511:551 Additionally, its seeds have excellent nutritional value, and the abundant lipids and polysaccharides in the seeds make this plant a potential valuable source of bio-energy. 27115614 1 5 dep BACKGROUND 82:91 arg1 plant 215:219 an important pioneer plant 194:219 an important pioneer plant that inhabits moving and semi-stable sand dunes in the deserts and steppes of northwest and north-central China 194:331 BACKGROUND Artemisia sphaerocephala, a semi-shrub belonging to the Artemisia genus of the Compositae family, is an important pioneer plant that inhabits moving and semi-stable sand dunes in the deserts and steppes of northwest and north-central China. 27115614 1 5 dep BACKGROUND 82:91 arg1 sphaerocephala 103:116 Artemisia sphaerocephala 93:116 Artemisia sphaerocephala 93:116 BACKGROUND Artemisia sphaerocephala, a semi-shrub belonging to the Artemisia genus of the Compositae family, is an important pioneer plant that inhabits moving and semi-stable sand dunes in the deserts and steppes of northwest and north-central China. 27115614 11 6 from mechanisms 1982:1991 arg1 plants 2029:2034 plants 2029:2034 plants 2029:2034 Identification of the key genes in the unsaturated fatty acid synthesis pathway could increase understanding of the biological regulatory mechanisms of fatty acid composition traits in plants and facilitate genetic manipulation of the fatty acid composition of oil crops. 27115614 11 7 theme composition 2007:2017 arg1 traits 2019:2024 fatty acid composition traits 1996:2024 fatty acid composition traits in plants 1996:2034 Identification of the key genes in the unsaturated fatty acid synthesis pathway could increase understanding of the biological regulatory mechanisms of fatty acid composition traits in plants and facilitate genetic manipulation of the fatty acid composition of oil crops. 27115614 2 8 from resilient 345:353 arg1 environments 366:377 extreme environments 358:377 extreme environments 358:377 It is very resilient in extreme environments. 27115614 4 9 theme environmental 664:676 arg1 capacity 689:696 environmental adaptation capacity 664:696 environmental adaptation capacity of A. sphaerocephala 664:717 However, partly due to the scarcity of genetic information, the genetic mechanisms controlling the traits and environmental adaptation capacity of A. sphaerocephala are unknown. 27115614 11 10 theme genetic 2051:2057 arg1 manipulation 2059:2070 genetic manipulation 2051:2070 genetic manipulation of the fatty acid composition of oil crops 2051:2113 Identification of the key genes in the unsaturated fatty acid synthesis pathway could increase understanding of the biological regulatory mechanisms of fatty acid composition traits in plants and facilitate genetic manipulation of the fatty acid composition of oil crops. 27115614 4 11 theme genetic 618:624 arg1 mechanisms 626:635 the genetic mechanisms 614:635 the genetic mechanisms controlling the traits and environmental adaptation capacity of A. sphaerocephala 614:717 However, partly due to the scarcity of genetic information, the genetic mechanisms controlling the traits and environmental adaptation capacity of A. sphaerocephala are unknown. 27115614 4 11 theme genetic 618:624 arg1 unknown 723:729 unknown 723:729 unknown 723:729 However, partly due to the scarcity of genetic information, the genetic mechanisms controlling the traits and environmental adaptation capacity of A. sphaerocephala are unknown. 27115614 10 12 theme current 1741:1747 arg1 understanding 1749:1761 the current understanding 1737:1761 the current understanding of molecular adaptive mechanisms of A. sphaerocephala in the desert environment 1737:1841 CONCLUSION The present work provides abundant genomic information for functional dissection of the important traits of A. sphaerocephala and contributes to the current understanding of molecular adaptive mechanisms of A. sphaerocephala in the desert environment. 27115614 1 13 theme pioneer 207:213 arg1 plant 215:219 an important pioneer plant 194:219 an important pioneer plant that inhabits moving and semi-stable sand dunes in the deserts and steppes of northwest and north-central China 194:331 BACKGROUND Artemisia sphaerocephala, a semi-shrub belonging to the Artemisia genus of the Compositae family, is an important pioneer plant that inhabits moving and semi-stable sand dunes in the deserts and steppes of northwest and north-central China. 27115614 1 13 theme pioneer 207:213 arg1 sphaerocephala 103:116 Artemisia sphaerocephala 93:116 Artemisia sphaerocephala 93:116 BACKGROUND Artemisia sphaerocephala, a semi-shrub belonging to the Artemisia genus of the Compositae family, is an important pioneer plant that inhabits moving and semi-stable sand dunes in the deserts and steppes of northwest and north-central China. 27115614 8 14 theme gene 1411:1414 arg1 family 1416:1421 the largest fad2 gene family 1394:1421 the largest fad2 gene family reported to date 1394:1438 We analyzed the key genes involved in the unsaturated fatty acid synthesis pathway and identified 26 A. sphaerocephala fad2 genes, which is the largest fad2 gene family reported to date. 27115614 8 14 theme gene 1411:1414 arg1 genes 1378:1382 26 A. sphaerocephala fad2 genes 1352:1382 26 A. sphaerocephala fad2 genes 1352:1382 We analyzed the key genes involved in the unsaturated fatty acid synthesis pathway and identified 26 A. sphaerocephala fad2 genes, which is the largest fad2 gene family reported to date. 27115614 11 15 theme unsaturated 1883:1893 arg1 acid 1901:1904 unsaturated fatty acid 1883:1904 the unsaturated fatty acid synthesis pathway 1879:1922 Identification of the key genes in the unsaturated fatty acid synthesis pathway could increase understanding of the biological regulatory mechanisms of fatty acid composition traits in plants and facilitate genetic manipulation of the fatty acid composition of oil crops. 27115614 11 16 theme biological 1960:1969 arg1 mechanisms 1982:1991 the biological regulatory mechanisms 1956:1991 the biological regulatory mechanisms of fatty acid composition traits in plants 1956:2034 Identification of the key genes in the unsaturated fatty acid synthesis pathway could increase understanding of the biological regulatory mechanisms of fatty acid composition traits in plants and facilitate genetic manipulation of the fatty acid composition of oil crops. 27115614 6 17 theme A. 959:960 arg1 sphaerocephala 962:975 desert-growing A. sphaerocephala 944:975 desert-growing A. sphaerocephala 944:975 To maximize the representation of conditional transcripts, mRNA was obtained from 17 samples, including living tissues of desert-growing A. sphaerocephala, seeds germinated in the laboratory, and calli subjected to no stress (control) and high and low temperature, high and low osmotic, and salt stresses. 27115614 11 18 from pathway 1916:1922 arg1 Identification 1844:1857 Identification 1844:1857 Identification of the key genes in the unsaturated fatty acid synthesis pathway 1844:1922 Identification of the key genes in the unsaturated fatty acid synthesis pathway could increase understanding of the biological regulatory mechanisms of fatty acid composition traits in plants and facilitate genetic manipulation of the fatty acid composition of oil crops. 27115614 8 19 theme key 1270:1272 arg1 genes 1274:1278 the key genes 1266:1278 the key genes involved in the unsaturated fatty acid synthesis pathway 1266:1335 We analyzed the key genes involved in the unsaturated fatty acid synthesis pathway and identified 26 A. sphaerocephala fad2 genes, which is the largest fad2 gene family reported to date. 27115614 10 20 theme adaptive 1776:1783 arg1 mechanisms 1785:1794 molecular adaptive mechanisms 1766:1794 molecular adaptive mechanisms of A. sphaerocephala in the desert environment 1766:1841 CONCLUSION The present work provides abundant genomic information for functional dissection of the important traits of A. sphaerocephala and contributes to the current understanding of molecular adaptive mechanisms of A. sphaerocephala in the desert environment. 27115614 11 21 theme acid 2085:2088 arg1 composition 2090:2100 the fatty acid composition 2075:2100 the fatty acid composition of oil crops 2075:2113 Identification of the key genes in the unsaturated fatty acid synthesis pathway could increase understanding of the biological regulatory mechanisms of fatty acid composition traits in plants and facilitate genetic manipulation of the fatty acid composition of oil crops. 27115614 11 22 theme fatty 1996:2000 arg1 traits 2019:2024 fatty acid composition traits 1996:2024 fatty acid composition traits in plants 1996:2034 Identification of the key genes in the unsaturated fatty acid synthesis pathway could increase understanding of the biological regulatory mechanisms of fatty acid composition traits in plants and facilitate genetic manipulation of the fatty acid composition of oil crops. 27115614 9 23 theme genes 1463:1467 arg1 genes 1463:1467 genes 1463:1467 genes responsible for resistance to extreme temperatures, salt, drought and a combination of stresses 1463:1563 Furthermore, a set of genes responsible for resistance to extreme temperatures, salt, drought and a combination of stresses was identified. 27115614 9 23 theme genes 1463:1467 arg1 set 1456:1458 a set 1454:1458 a set of genes responsible for resistance to extreme temperatures, salt, drought and a combination of stresses 1454:1563 Furthermore, a set of genes responsible for resistance to extreme temperatures, salt, drought and a combination of stresses was identified. 27115614 11 24 theme fatty 1895:1899 arg1 acid 1901:1904 unsaturated fatty acid 1883:1904 the unsaturated fatty acid synthesis pathway 1879:1922 Identification of the key genes in the unsaturated fatty acid synthesis pathway could increase understanding of the biological regulatory mechanisms of fatty acid composition traits in plants and facilitate genetic manipulation of the fatty acid composition of oil crops. 27115614 0 25 theme sphaerocephala 66:79 arg1 Analysis 27:34 Genome-Scale Transcriptome Analysis 0:34 Genome-Scale Transcriptome Analysis of the Desert Shrub Artemisia sphaerocephala. 0:80 Genome-Scale Transcriptome Analysis of the Desert Shrub Artemisia sphaerocephala. 27115614 10 26 theme sphaerocephala 1802:1815 arg1 mechanisms 1785:1794 molecular adaptive mechanisms 1766:1794 molecular adaptive mechanisms of A. sphaerocephala in the desert environment 1766:1841 CONCLUSION The present work provides abundant genomic information for functional dissection of the important traits of A. sphaerocephala and contributes to the current understanding of molecular adaptive mechanisms of A. sphaerocephala in the desert environment. 27115614 10 27 from understanding 1749:1761 arg1 environment 1831:1841 the desert environment 1820:1841 the desert environment 1820:1841 CONCLUSION The present work provides abundant genomic information for functional dissection of the important traits of A. sphaerocephala and contributes to the current understanding of molecular adaptive mechanisms of A. sphaerocephala in the desert environment. 27115614 8 28 theme fatty 1308:1312 arg1 acid 1314:1317 unsaturated fatty acid 1296:1317 the unsaturated fatty acid synthesis pathway 1292:1335 We analyzed the key genes involved in the unsaturated fatty acid synthesis pathway and identified 26 A. sphaerocephala fad2 genes, which is the largest fad2 gene family reported to date. 27115614 5 29 theme in-depth 767:774 arg1 analysis 791:798 the first in-depth transcriptomic analysis 757:798 the first in-depth transcriptomic analysis of A. sphaerocephala 757:819 RESULTS Here, we present the first in-depth transcriptomic analysis of A. sphaerocephala. 27115614 1 30 theme Compositae 172:181 arg1 family 183:188 the Compositae family 168:188 the Compositae family 168:188 BACKGROUND Artemisia sphaerocephala, a semi-shrub belonging to the Artemisia genus of the Compositae family, is an important pioneer plant that inhabits moving and semi-stable sand dunes in the deserts and steppes of northwest and north-central China. 27115614 8 31 theme synthesis 1319:1327 arg1 pathway 1329:1335 the unsaturated fatty acid synthesis pathway 1292:1335 the unsaturated fatty acid synthesis pathway 1292:1335 We analyzed the key genes involved in the unsaturated fatty acid synthesis pathway and identified 26 A. sphaerocephala fad2 genes, which is the largest fad2 gene family reported to date. 27115614 7 32 theme HiSeq 1187:1191 arg1 platform 1198:1205 an Illumina HiSeq 2500 platform 1175:1205 an Illumina HiSeq 2500 platform 1175:1205 De novo transcriptome assembly performed using an Illumina HiSeq 2500 platform resulted in the generation of 68,373 unigenes. 27115614 10 33 from mechanisms 1785:1794 arg1 environment 1831:1841 the desert environment 1820:1841 the desert environment 1820:1841 CONCLUSION The present work provides abundant genomic information for functional dissection of the important traits of A. sphaerocephala and contributes to the current understanding of molecular adaptive mechanisms of A. sphaerocephala in the desert environment. 27115614 1 34 theme Artemisia 149:157 arg1 genus 159:163 the Artemisia genus 145:163 the Artemisia genus of the Compositae family 145:188 BACKGROUND Artemisia sphaerocephala, a semi-shrub belonging to the Artemisia genus of the Compositae family, is an important pioneer plant that inhabits moving and semi-stable sand dunes in the deserts and steppes of northwest and north-central China. 27115614 10 35 theme abundant 1618:1625 arg1 information 1635:1645 abundant genomic information 1618:1645 abundant genomic information for functional dissection of the important traits of A. sphaerocephala 1618:1716 CONCLUSION The present work provides abundant genomic information for functional dissection of the important traits of A. sphaerocephala and contributes to the current understanding of molecular adaptive mechanisms of A. sphaerocephala in the desert environment. 27115614 5 36 theme transcriptomic 776:789 arg1 analysis 791:798 the first in-depth transcriptomic analysis 757:798 the first in-depth transcriptomic analysis of A. sphaerocephala 757:819 RESULTS Here, we present the first in-depth transcriptomic analysis of A. sphaerocephala. 27115614 1 37 theme Artemisia 93:101 arg1 plant 215:219 an important pioneer plant 194:219 an important pioneer plant that inhabits moving and semi-stable sand dunes in the deserts and steppes of northwest and north-central China 194:331 BACKGROUND Artemisia sphaerocephala, a semi-shrub belonging to the Artemisia genus of the Compositae family, is an important pioneer plant that inhabits moving and semi-stable sand dunes in the deserts and steppes of northwest and north-central China. 27115614 1 37 theme Artemisia 93:101 arg1 sphaerocephala 103:116 Artemisia sphaerocephala 93:116 Artemisia sphaerocephala 93:116 BACKGROUND Artemisia sphaerocephala, a semi-shrub belonging to the Artemisia genus of the Compositae family, is an important pioneer plant that inhabits moving and semi-stable sand dunes in the deserts and steppes of northwest and north-central China. 27115614 1 37 theme Artemisia 93:101 arg1 semi-shrub 121:130 a semi-shrub 119:130 a semi-shrub belonging to the Artemisia genus of the Compositae family 119:188 BACKGROUND Artemisia sphaerocephala, a semi-shrub belonging to the Artemisia genus of the Compositae family, is an important pioneer plant that inhabits moving and semi-stable sand dunes in the deserts and steppes of northwest and north-central China. 27115614 0 38 theme Genome-Scale 0:11 arg1 Analysis 27:34 Genome-Scale Transcriptome Analysis 0:34 Genome-Scale Transcriptome Analysis of the Desert Shrub Artemisia sphaerocephala. 0:80 Genome-Scale Transcriptome Analysis of the Desert Shrub Artemisia sphaerocephala. 27115614 8 39 theme sphaerocephala 1358:1371 arg1 genes 1378:1382 26 A. sphaerocephala fad2 genes 1352:1382 26 A. sphaerocephala fad2 genes 1352:1382 We analyzed the key genes involved in the unsaturated fatty acid synthesis pathway and identified 26 A. sphaerocephala fad2 genes, which is the largest fad2 gene family reported to date. 27115614 8 39 theme sphaerocephala 1358:1371 arg1 family 1416:1421 the largest fad2 gene family 1394:1421 the largest fad2 gene family reported to date 1394:1438 We analyzed the key genes involved in the unsaturated fatty acid synthesis pathway and identified 26 A. sphaerocephala fad2 genes, which is the largest fad2 gene family reported to date. 27115614 10 40 theme functional 1651:1660 arg1 dissection 1662:1671 functional dissection 1651:1671 functional dissection of the important traits of A. sphaerocephala 1651:1716 CONCLUSION The present work provides abundant genomic information for functional dissection of the important traits of A. sphaerocephala and contributes to the current understanding of molecular adaptive mechanisms of A. sphaerocephala in the desert environment. 27115614 7 41 theme transcriptome 1136:1148 arg1 assembly 1150:1157 De novo transcriptome assembly 1128:1157 De novo transcriptome assembly performed using an Illumina HiSeq 2500 platform 1128:1205 De novo transcriptome assembly performed using an Illumina HiSeq 2500 platform resulted in the generation of 68,373 unigenes. 27115614 11 42 theme acid 2002:2005 arg1 traits 2019:2024 fatty acid composition traits 1996:2024 fatty acid composition traits in plants 1996:2034 Identification of the key genes in the unsaturated fatty acid synthesis pathway could increase understanding of the biological regulatory mechanisms of fatty acid composition traits in plants and facilitate genetic manipulation of the fatty acid composition of oil crops. 27115614 3 43 theme excellent 409:417 arg1 value 431:435 excellent nutritional value 409:435 excellent nutritional value 409:435 Additionally, its seeds have excellent nutritional value, and the abundant lipids and polysaccharides in the seeds make this plant a potential valuable source of bio-energy. 27115614 11 44 theme synthesis 1906:1914 arg1 pathway 1916:1922 the unsaturated fatty acid synthesis pathway 1879:1922 the unsaturated fatty acid synthesis pathway 1879:1922 Identification of the key genes in the unsaturated fatty acid synthesis pathway could increase understanding of the biological regulatory mechanisms of fatty acid composition traits in plants and facilitate genetic manipulation of the fatty acid composition of oil crops. 27115614 3 45 theme abundant 446:453 arg1 lipids 455:460 the abundant lipids 442:460 the abundant lipids 442:460 Additionally, its seeds have excellent nutritional value, and the abundant lipids and polysaccharides in the seeds make this plant a potential valuable source of bio-energy. 27115614 7 46 theme De 1128:1129 arg1 assembly 1150:1157 De novo transcriptome assembly 1128:1157 De novo transcriptome assembly performed using an Illumina HiSeq 2500 platform 1128:1205 De novo transcriptome assembly performed using an Illumina HiSeq 2500 platform resulted in the generation of 68,373 unigenes. 27115614 1 47 theme northwest 299:307 arg1 China 327:331 northwest and north-central China 299:331 northwest and north-central China 299:331 BACKGROUND Artemisia sphaerocephala, a semi-shrub belonging to the Artemisia genus of the Compositae family, is an important pioneer plant that inhabits moving and semi-stable sand dunes in the deserts and steppes of northwest and north-central China. 27115614 3 48 from lipids 455:460 arg1 seeds 489:493 the seeds 485:493 the seeds 485:493 Additionally, its seeds have excellent nutritional value, and the abundant lipids and polysaccharides in the seeds make this plant a potential valuable source of bio-energy. 27115614 10 49 theme important 1680:1688 arg1 traits 1690:1695 the important traits 1676:1695 the important traits of A. sphaerocephala 1676:1716 CONCLUSION The present work provides abundant genomic information for functional dissection of the important traits of A. sphaerocephala and contributes to the current understanding of molecular adaptive mechanisms of A. sphaerocephala in the desert environment. 27115614 0 50 theme Shrub 50:54 arg1 sphaerocephala 66:79 the Desert Shrub Artemisia sphaerocephala 39:79 the Desert Shrub Artemisia sphaerocephala 39:79 Genome-Scale Transcriptome Analysis of the Desert Shrub Artemisia sphaerocephala. 27115614 1 51 theme north-central 313:325 arg1 China 327:331 northwest and north-central China 299:331 northwest and north-central China 299:331 BACKGROUND Artemisia sphaerocephala, a semi-shrub belonging to the Artemisia genus of the Compositae family, is an important pioneer plant that inhabits moving and semi-stable sand dunes in the deserts and steppes of northwest and north-central China. 27115614 6 52 theme conditional 856:866 arg1 transcripts 868:878 conditional transcripts 856:878 conditional transcripts 856:878 To maximize the representation of conditional transcripts, mRNA was obtained from 17 samples, including living tissues of desert-growing A. sphaerocephala, seeds germinated in the laboratory, and calli subjected to no stress (control) and high and low temperature, high and low osmotic, and salt stresses. 27115614 11 53 from plants 2029:2034 arg1 mechanisms 1982:1991 the biological regulatory mechanisms 1956:1991 the biological regulatory mechanisms of fatty acid composition traits in plants 1956:2034 Identification of the key genes in the unsaturated fatty acid synthesis pathway could increase understanding of the biological regulatory mechanisms of fatty acid composition traits in plants and facilitate genetic manipulation of the fatty acid composition of oil crops. 27115614 11 54 theme mechanisms 1982:1991 arg1 understanding 1939:1951 understanding 1939:1951 understanding of the biological regulatory mechanisms of fatty acid composition traits in plants 1939:2034 Identification of the key genes in the unsaturated fatty acid synthesis pathway could increase understanding of the biological regulatory mechanisms of fatty acid composition traits in plants and facilitate genetic manipulation of the fatty acid composition of oil crops. 27115614 3 55 from polysaccharides 466:480 arg1 seeds 489:493 the seeds 485:493 the seeds 485:493 Additionally, its seeds have excellent nutritional value, and the abundant lipids and polysaccharides in the seeds make this plant a potential valuable source of bio-energy. 27115614 6 56 theme low 1096:1098 arg1 osmotic 1100:1106 high and low osmotic 1087:1106 high and low osmotic 1087:1106 To maximize the representation of conditional transcripts, mRNA was obtained from 17 samples, including living tissues of desert-growing A. sphaerocephala, seeds germinated in the laboratory, and calli subjected to no stress (control) and high and low temperature, high and low osmotic, and salt stresses. 27115614 6 57 theme high 1087:1090 arg1 osmotic 1100:1106 high and low osmotic 1087:1106 high and low osmotic 1087:1106 To maximize the representation of conditional transcripts, mRNA was obtained from 17 samples, including living tissues of desert-growing A. sphaerocephala, seeds germinated in the laboratory, and calli subjected to no stress (control) and high and low temperature, high and low osmotic, and salt stresses. 27115614 8 58 theme fad2 1406:1409 arg1 family 1416:1421 the largest fad2 gene family 1394:1421 the largest fad2 gene family reported to date 1394:1438 We analyzed the key genes involved in the unsaturated fatty acid synthesis pathway and identified 26 A. sphaerocephala fad2 genes, which is the largest fad2 gene family reported to date. 27115614 8 58 theme fad2 1406:1409 arg1 genes 1378:1382 26 A. sphaerocephala fad2 genes 1352:1382 26 A. sphaerocephala fad2 genes 1352:1382 We analyzed the key genes involved in the unsaturated fatty acid synthesis pathway and identified 26 A. sphaerocephala fad2 genes, which is the largest fad2 gene family reported to date. 27115614 10 59 theme sphaerocephala 1703:1716 arg1 traits 1690:1695 the important traits 1676:1695 the important traits of A. sphaerocephala 1676:1716 CONCLUSION The present work provides abundant genomic information for functional dissection of the important traits of A. sphaerocephala and contributes to the current understanding of molecular adaptive mechanisms of A. sphaerocephala in the desert environment. 27115614 10 60 from environment 1831:1841 arg1 understanding 1749:1761 the current understanding 1737:1761 the current understanding of molecular adaptive mechanisms of A. sphaerocephala in the desert environment 1737:1841 CONCLUSION The present work provides abundant genomic information for functional dissection of the important traits of A. sphaerocephala and contributes to the current understanding of molecular adaptive mechanisms of A. sphaerocephala in the desert environment. 27115614 7 61 theme 68,373 1237:1242 arg1 unigenes 1244:1251 68,373 unigenes 1237:1251 68,373 unigenes 1237:1251 De novo transcriptome assembly performed using an Illumina HiSeq 2500 platform resulted in the generation of 68,373 unigenes. 27115614 4 62 theme information 601:611 arg1 scarcity 581:588 the scarcity 577:588 the scarcity of genetic information 577:611 However, partly due to the scarcity of genetic information, the genetic mechanisms controlling the traits and environmental adaptation capacity of A. sphaerocephala are unknown. 27115614 7 63 theme 2500 1193:1196 arg1 platform 1198:1205 an Illumina HiSeq 2500 platform 1175:1205 an Illumina HiSeq 2500 platform 1175:1205 De novo transcriptome assembly performed using an Illumina HiSeq 2500 platform resulted in the generation of 68,373 unigenes. 27115614 1 64 theme sand 258:261 arg1 dunes 263:267 moving and semi-stable sand dunes 235:267 moving and semi-stable sand dunes 235:267 BACKGROUND Artemisia sphaerocephala, a semi-shrub belonging to the Artemisia genus of the Compositae family, is an important pioneer plant that inhabits moving and semi-stable sand dunes in the deserts and steppes of northwest and north-central China. 27115614 3 65 contain have 404:407 arg2 value 431:435 excellent nutritional value 409:435 excellent nutritional value 409:435 Additionally, its seeds have excellent nutritional value, and the abundant lipids and polysaccharides in the seeds make this plant a potential valuable source of bio-energy. 27115614 3 65 contain have 404:407 arg1 seeds 398:402 its seeds 394:402 its seeds 394:402 Additionally, its seeds have excellent nutritional value, and the abundant lipids and polysaccharides in the seeds make this plant a potential valuable source of bio-energy. 27115614 11 66 from traits 2019:2024 arg1 plants 2029:2034 plants 2029:2034 plants 2029:2034 Identification of the key genes in the unsaturated fatty acid synthesis pathway could increase understanding of the biological regulatory mechanisms of fatty acid composition traits in plants and facilitate genetic manipulation of the fatty acid composition of oil crops. 27115614 11 67 theme traits 2019:2024 arg1 mechanisms 1982:1991 the biological regulatory mechanisms 1956:1991 the biological regulatory mechanisms of fatty acid composition traits in plants 1956:2034 Identification of the key genes in the unsaturated fatty acid synthesis pathway could increase understanding of the biological regulatory mechanisms of fatty acid composition traits in plants and facilitate genetic manipulation of the fatty acid composition of oil crops. 27115614 3 68 theme valuable 523:530 arg1 source 532:537 a potential valuable source 511:537 a potential valuable source of bio-energy 511:551 Additionally, its seeds have excellent nutritional value, and the abundant lipids and polysaccharides in the seeds make this plant a potential valuable source of bio-energy. 27115614 1 69 theme family 183:188 arg1 genus 159:163 the Artemisia genus 145:163 the Artemisia genus of the Compositae family 145:188 BACKGROUND Artemisia sphaerocephala, a semi-shrub belonging to the Artemisia genus of the Compositae family, is an important pioneer plant that inhabits moving and semi-stable sand dunes in the deserts and steppes of northwest and north-central China. 27115614 10 70 theme molecular 1766:1774 arg1 mechanisms 1785:1794 molecular adaptive mechanisms 1766:1794 molecular adaptive mechanisms of A. sphaerocephala in the desert environment 1766:1841 CONCLUSION The present work provides abundant genomic information for functional dissection of the important traits of A. sphaerocephala and contributes to the current understanding of molecular adaptive mechanisms of A. sphaerocephala in the desert environment. 27115614 2 71 from environments 366:377 arg1 resilient 345:353 resilient 345:353 resilient 345:353 It is very resilient in extreme environments. 27115614 1 72 theme important 197:205 arg1 plant 215:219 an important pioneer plant 194:219 an important pioneer plant that inhabits moving and semi-stable sand dunes in the deserts and steppes of northwest and north-central China 194:331 BACKGROUND Artemisia sphaerocephala, a semi-shrub belonging to the Artemisia genus of the Compositae family, is an important pioneer plant that inhabits moving and semi-stable sand dunes in the deserts and steppes of northwest and north-central China. 27115614 1 72 theme important 197:205 arg1 sphaerocephala 103:116 Artemisia sphaerocephala 93:116 Artemisia sphaerocephala 93:116 BACKGROUND Artemisia sphaerocephala, a semi-shrub belonging to the Artemisia genus of the Compositae family, is an important pioneer plant that inhabits moving and semi-stable sand dunes in the deserts and steppes of northwest and north-central China. 27115614 11 73 theme fatty 2079:2083 arg1 composition 2090:2100 the fatty acid composition 2075:2100 the fatty acid composition of oil crops 2075:2113 Identification of the key genes in the unsaturated fatty acid synthesis pathway could increase understanding of the biological regulatory mechanisms of fatty acid composition traits in plants and facilitate genetic manipulation of the fatty acid composition of oil crops. 27115614 6 74 theme salt 1113:1116 arg1 stresses 1118:1125 salt stresses 1113:1125 salt stresses 1113:1125 To maximize the representation of conditional transcripts, mRNA was obtained from 17 samples, including living tissues of desert-growing A. sphaerocephala, seeds germinated in the laboratory, and calli subjected to no stress (control) and high and low temperature, high and low osmotic, and salt stresses. 27115614 6 75 theme sphaerocephala 962:975 arg1 seeds 978:982 seeds 978:982 seeds germinated in the laboratory 978:1011 To maximize the representation of conditional transcripts, mRNA was obtained from 17 samples, including living tissues of desert-growing A. sphaerocephala, seeds germinated in the laboratory, and calli subjected to no stress (control) and high and low temperature, high and low osmotic, and salt stresses. 27115614 6 75 theme sphaerocephala 962:975 arg1 calli 1018:1022 calli 1018:1022 calli subjected to no stress (control) and high and low temperature, high and low osmotic, and salt stresses 1018:1125 To maximize the representation of conditional transcripts, mRNA was obtained from 17 samples, including living tissues of desert-growing A. sphaerocephala, seeds germinated in the laboratory, and calli subjected to no stress (control) and high and low temperature, high and low osmotic, and salt stresses. 27115614 6 75 theme sphaerocephala 962:975 arg1 tissues 933:939 living tissues 926:939 living tissues of desert-growing A. sphaerocephala 926:975 To maximize the representation of conditional transcripts, mRNA was obtained from 17 samples, including living tissues of desert-growing A. sphaerocephala, seeds germinated in the laboratory, and calli subjected to no stress (control) and high and low temperature, high and low osmotic, and salt stresses. 27115614 10 76 theme mechanisms 1785:1794 arg1 understanding 1749:1761 the current understanding 1737:1761 the current understanding of molecular adaptive mechanisms of A. sphaerocephala in the desert environment 1737:1841 CONCLUSION The present work provides abundant genomic information for functional dissection of the important traits of A. sphaerocephala and contributes to the current understanding of molecular adaptive mechanisms of A. sphaerocephala in the desert environment. 27115614 10 77 theme A. 1700:1701 arg1 sphaerocephala 1703:1716 A. sphaerocephala 1700:1716 A. sphaerocephala 1700:1716 CONCLUSION The present work provides abundant genomic information for functional dissection of the important traits of A. sphaerocephala and contributes to the current understanding of molecular adaptive mechanisms of A. sphaerocephala in the desert environment. 27115614 6 78 theme desert-growing 944:957 arg1 sphaerocephala 962:975 desert-growing A. sphaerocephala 944:975 desert-growing A. sphaerocephala 944:975 To maximize the representation of conditional transcripts, mRNA was obtained from 17 samples, including living tissues of desert-growing A. sphaerocephala, seeds germinated in the laboratory, and calli subjected to no stress (control) and high and low temperature, high and low osmotic, and salt stresses. 27115614 11 79 theme oil 2105:2107 arg1 crops 2109:2113 oil crops 2105:2113 oil crops 2105:2113 Identification of the key genes in the unsaturated fatty acid synthesis pathway could increase understanding of the biological regulatory mechanisms of fatty acid composition traits in plants and facilitate genetic manipulation of the fatty acid composition of oil crops. 27115614 4 80 theme sphaerocephala 704:717 arg1 traits 653:658 the traits 649:658 the traits 649:658 However, partly due to the scarcity of genetic information, the genetic mechanisms controlling the traits and environmental adaptation capacity of A. sphaerocephala are unknown. 27115614 4 80 theme sphaerocephala 704:717 arg1 capacity 689:696 environmental adaptation capacity 664:696 environmental adaptation capacity of A. sphaerocephala 664:717 However, partly due to the scarcity of genetic information, the genetic mechanisms controlling the traits and environmental adaptation capacity of A. sphaerocephala are unknown. 27115614 10 81 theme desert 1824:1829 arg1 environment 1831:1841 the desert environment 1820:1841 the desert environment 1820:1841 CONCLUSION The present work provides abundant genomic information for functional dissection of the important traits of A. sphaerocephala and contributes to the current understanding of molecular adaptive mechanisms of A. sphaerocephala in the desert environment. 27115614 11 82 theme composition 2090:2100 arg1 manipulation 2059:2070 genetic manipulation 2051:2070 genetic manipulation of the fatty acid composition of oil crops 2051:2113 Identification of the key genes in the unsaturated fatty acid synthesis pathway could increase understanding of the biological regulatory mechanisms of fatty acid composition traits in plants and facilitate genetic manipulation of the fatty acid composition of oil crops. 27115614 11 83 theme regulatory 1971:1980 arg1 mechanisms 1982:1991 the biological regulatory mechanisms 1956:1991 the biological regulatory mechanisms of fatty acid composition traits in plants 1956:2034 Identification of the key genes in the unsaturated fatty acid synthesis pathway could increase understanding of the biological regulatory mechanisms of fatty acid composition traits in plants and facilitate genetic manipulation of the fatty acid composition of oil crops. 27115614 9 84 theme responsible 1469:1479 arg1 genes 1463:1467 genes 1463:1467 genes responsible for resistance to extreme temperatures, salt, drought and a combination of stresses 1463:1563 Furthermore, a set of genes responsible for resistance to extreme temperatures, salt, drought and a combination of stresses was identified. 27115614 4 85 theme adaptation 678:687 arg1 capacity 689:696 environmental adaptation capacity 664:696 environmental adaptation capacity of A. sphaerocephala 664:717 However, partly due to the scarcity of genetic information, the genetic mechanisms controlling the traits and environmental adaptation capacity of A. sphaerocephala are unknown. 27115614 5 86 theme first 761:765 arg1 analysis 791:798 the first in-depth transcriptomic analysis 757:798 the first in-depth transcriptomic analysis of A. sphaerocephala 757:819 RESULTS Here, we present the first in-depth transcriptomic analysis of A. sphaerocephala. 27115614 11 87 theme key 1866:1868 arg1 genes 1870:1874 the key genes 1862:1874 the key genes in the unsaturated fatty acid synthesis pathway 1862:1922 Identification of the key genes in the unsaturated fatty acid synthesis pathway could increase understanding of the biological regulatory mechanisms of fatty acid composition traits in plants and facilitate genetic manipulation of the fatty acid composition of oil crops. 27115614 1 88 dep deserts 276:282 arg1 the 272:274 the 272:274 the 272:274 BACKGROUND Artemisia sphaerocephala, a semi-shrub belonging to the Artemisia genus of the Compositae family, is an important pioneer plant that inhabits moving and semi-stable sand dunes in the deserts and steppes of northwest and north-central China. 27115614 8 89 theme unsaturated 1296:1306 arg1 acid 1314:1317 unsaturated fatty acid 1296:1317 the unsaturated fatty acid synthesis pathway 1292:1335 We analyzed the key genes involved in the unsaturated fatty acid synthesis pathway and identified 26 A. sphaerocephala fad2 genes, which is the largest fad2 gene family reported to date. 27115614 7 90 theme Illumina 1178:1185 arg1 platform 1198:1205 an Illumina HiSeq 2500 platform 1175:1205 an Illumina HiSeq 2500 platform 1175:1205 De novo transcriptome assembly performed using an Illumina HiSeq 2500 platform resulted in the generation of 68,373 unigenes. 27115614 9 91 theme extreme 1499:1505 arg1 temperatures 1507:1518 extreme temperatures 1499:1518 extreme temperatures 1499:1518 Furthermore, a set of genes responsible for resistance to extreme temperatures, salt, drought and a combination of stresses was identified. 27115614 11 92 from genes 1870:1874 arg1 pathway 1916:1922 the unsaturated fatty acid synthesis pathway 1879:1922 the unsaturated fatty acid synthesis pathway 1879:1922 Identification of the key genes in the unsaturated fatty acid synthesis pathway could increase understanding of the biological regulatory mechanisms of fatty acid composition traits in plants and facilitate genetic manipulation of the fatty acid composition of oil crops. 27115614 8 93 theme acid 1314:1317 arg1 pathway 1329:1335 the unsaturated fatty acid synthesis pathway 1292:1335 the unsaturated fatty acid synthesis pathway 1292:1335 We analyzed the key genes involved in the unsaturated fatty acid synthesis pathway and identified 26 A. sphaerocephala fad2 genes, which is the largest fad2 gene family reported to date. 27115614 6 94 theme low 1070:1072 arg1 temperature 1074:1084 high and low temperature 1061:1084 high and low temperature 1061:1084 To maximize the representation of conditional transcripts, mRNA was obtained from 17 samples, including living tissues of desert-growing A. sphaerocephala, seeds germinated in the laboratory, and calli subjected to no stress (control) and high and low temperature, high and low osmotic, and salt stresses. 27115614 11 95 theme acid 1901:1904 arg1 pathway 1916:1922 the unsaturated fatty acid synthesis pathway 1879:1922 the unsaturated fatty acid synthesis pathway 1879:1922 Identification of the key genes in the unsaturated fatty acid synthesis pathway could increase understanding of the biological regulatory mechanisms of fatty acid composition traits in plants and facilitate genetic manipulation of the fatty acid composition of oil crops. 27115614 5 96 theme sphaerocephala 806:819 arg1 analysis 791:798 the first in-depth transcriptomic analysis 757:798 the first in-depth transcriptomic analysis of A. sphaerocephala 757:819 RESULTS Here, we present the first in-depth transcriptomic analysis of A. sphaerocephala. 27115614 6 97 theme high 1061:1064 arg1 temperature 1074:1084 high and low temperature 1061:1084 high and low temperature 1061:1084 To maximize the representation of conditional transcripts, mRNA was obtained from 17 samples, including living tissues of desert-growing A. sphaerocephala, seeds germinated in the laboratory, and calli subjected to no stress (control) and high and low temperature, high and low osmotic, and salt stresses. 27115614 7 98 dep De 1128:1129 arg1 novo 1131:1134 novo 1131:1134 novo 1131:1134 De novo transcriptome assembly performed using an Illumina HiSeq 2500 platform resulted in the generation of 68,373 unigenes. 27115614 11 99 from Identification 1844:1857 arg1 pathway 1916:1922 the unsaturated fatty acid synthesis pathway 1879:1922 the unsaturated fatty acid synthesis pathway 1879:1922 Identification of the key genes in the unsaturated fatty acid synthesis pathway could increase understanding of the biological regulatory mechanisms of fatty acid composition traits in plants and facilitate genetic manipulation of the fatty acid composition of oil crops. 27115614 10 100 theme present 1596:1602 arg1 work 1604:1607 The present work 1592:1607 The present work 1592:1607 CONCLUSION The present work provides abundant genomic information for functional dissection of the important traits of A. sphaerocephala and contributes to the current understanding of molecular adaptive mechanisms of A. sphaerocephala in the desert environment. 27115614 8 101 theme A. 1355:1356 arg1 genes 1378:1382 26 A. sphaerocephala fad2 genes 1352:1382 26 A. sphaerocephala fad2 genes 1352:1382 We analyzed the key genes involved in the unsaturated fatty acid synthesis pathway and identified 26 A. sphaerocephala fad2 genes, which is the largest fad2 gene family reported to date. 27115614 8 101 theme A. 1355:1356 arg1 family 1416:1421 the largest fad2 gene family 1394:1421 the largest fad2 gene family reported to date 1394:1438 We analyzed the key genes involved in the unsaturated fatty acid synthesis pathway and identified 26 A. sphaerocephala fad2 genes, which is the largest fad2 gene family reported to date. 27115614 11 102 theme genes 1870:1874 arg1 Identification 1844:1857 Identification 1844:1857 Identification of the key genes in the unsaturated fatty acid synthesis pathway 1844:1922 Identification of the key genes in the unsaturated fatty acid synthesis pathway could increase understanding of the biological regulatory mechanisms of fatty acid composition traits in plants and facilitate genetic manipulation of the fatty acid composition of oil crops. 27115614 0 103 theme Desert 43:48 arg1 sphaerocephala 66:79 the Desert Shrub Artemisia sphaerocephala 39:79 the Desert Shrub Artemisia sphaerocephala 39:79 Genome-Scale Transcriptome Analysis of the Desert Shrub Artemisia sphaerocephala. 27115614 3 104 theme nutritional 419:429 arg1 value 431:435 excellent nutritional value 409:435 excellent nutritional value 409:435 Additionally, its seeds have excellent nutritional value, and the abundant lipids and polysaccharides in the seeds make this plant a potential valuable source of bio-energy. 27115614 8 105 theme fad2 1373:1376 arg1 genes 1378:1382 26 A. sphaerocephala fad2 genes 1352:1382 26 A. sphaerocephala fad2 genes 1352:1382 We analyzed the key genes involved in the unsaturated fatty acid synthesis pathway and identified 26 A. sphaerocephala fad2 genes, which is the largest fad2 gene family reported to date. 27115614 8 105 theme fad2 1373:1376 arg1 family 1416:1421 the largest fad2 gene family 1394:1421 the largest fad2 gene family reported to date 1394:1438 We analyzed the key genes involved in the unsaturated fatty acid synthesis pathway and identified 26 A. sphaerocephala fad2 genes, which is the largest fad2 gene family reported to date. 27115614 10 106 theme genomic 1627:1633 arg1 information 1635:1645 abundant genomic information 1618:1645 abundant genomic information for functional dissection of the important traits of A. sphaerocephala 1618:1716 CONCLUSION The present work provides abundant genomic information for functional dissection of the important traits of A. sphaerocephala and contributes to the current understanding of molecular adaptive mechanisms of A. sphaerocephala in the desert environment. 27115614 0 107 theme Artemisia 56:64 arg1 sphaerocephala 66:79 the Desert Shrub Artemisia sphaerocephala 39:79 the Desert Shrub Artemisia sphaerocephala 39:79 Genome-Scale Transcriptome Analysis of the Desert Shrub Artemisia sphaerocephala. 27115614 6 108 theme transcripts 868:878 arg1 representation 838:851 the representation 834:851 the representation of conditional transcripts 834:878 To maximize the representation of conditional transcripts, mRNA was obtained from 17 samples, including living tissues of desert-growing A. sphaerocephala, seeds germinated in the laboratory, and calli subjected to no stress (control) and high and low temperature, high and low osmotic, and salt stresses. 27115614 9 109 theme stresses 1556:1563 arg1 drought 1527:1533 drought 1527:1533 drought 1527:1533 Furthermore, a set of genes responsible for resistance to extreme temperatures, salt, drought and a combination of stresses was identified. 27115614 9 109 theme stresses 1556:1563 arg1 combination 1541:1551 a combination 1539:1551 a combination of stresses 1539:1563 Furthermore, a set of genes responsible for resistance to extreme temperatures, salt, drought and a combination of stresses was identified. 27115614 9 109 theme stresses 1556:1563 arg1 salt 1521:1524 salt 1521:1524 salt 1521:1524 Furthermore, a set of genes responsible for resistance to extreme temperatures, salt, drought and a combination of stresses was identified. 27115614 9 109 theme stresses 1556:1563 arg1 resistance 1485:1494 resistance 1485:1494 resistance to extreme temperatures 1485:1518 Furthermore, a set of genes responsible for resistance to extreme temperatures, salt, drought and a combination of stresses was identified. 27115614 2 110 theme extreme 358:364 arg1 environments 366:377 extreme environments 358:377 extreme environments 358:377 It is very resilient in extreme environments. 27115614 1 111 theme China 327:331 arg1 steppes 288:294 steppes 288:294 steppes 288:294 BACKGROUND Artemisia sphaerocephala, a semi-shrub belonging to the Artemisia genus of the Compositae family, is an important pioneer plant that inhabits moving and semi-stable sand dunes in the deserts and steppes of northwest and north-central China. 27115614 1 111 theme China 327:331 arg1 deserts 276:282 deserts 276:282 deserts 276:282 BACKGROUND Artemisia sphaerocephala, a semi-shrub belonging to the Artemisia genus of the Compositae family, is an important pioneer plant that inhabits moving and semi-stable sand dunes in the deserts and steppes of northwest and north-central China. 27115614 7 112 theme unigenes 1244:1251 arg1 generation 1223:1232 the generation 1219:1232 the generation of 68,373 unigenes 1219:1251 De novo transcriptome assembly performed using an Illumina HiSeq 2500 platform resulted in the generation of 68,373 unigenes. 27115614 4 113 theme genetic 593:599 arg1 information 601:611 genetic information 593:611 genetic information 593:611 However, partly due to the scarcity of genetic information, the genetic mechanisms controlling the traits and environmental adaptation capacity of A. sphaerocephala are unknown. 27115614 3 114 theme potential 513:521 arg1 source 532:537 a potential valuable source 511:537 a potential valuable source of bio-energy 511:551 Additionally, its seeds have excellent nutritional value, and the abundant lipids and polysaccharides in the seeds make this plant a potential valuable source of bio-energy. 27115614 1 115 theme moving 235:240 arg1 dunes 263:267 moving and semi-stable sand dunes 235:267 moving and semi-stable sand dunes 235:267 BACKGROUND Artemisia sphaerocephala, a semi-shrub belonging to the Artemisia genus of the Compositae family, is an important pioneer plant that inhabits moving and semi-stable sand dunes in the deserts and steppes of northwest and north-central China. 27115614 8 116 theme largest 1398:1404 arg1 family 1416:1421 the largest fad2 gene family 1394:1421 the largest fad2 gene family reported to date 1394:1438 We analyzed the key genes involved in the unsaturated fatty acid synthesis pathway and identified 26 A. sphaerocephala fad2 genes, which is the largest fad2 gene family reported to date. 27115614 8 116 theme largest 1398:1404 arg1 genes 1378:1382 26 A. sphaerocephala fad2 genes 1352:1382 26 A. sphaerocephala fad2 genes 1352:1382 We analyzed the key genes involved in the unsaturated fatty acid synthesis pathway and identified 26 A. sphaerocephala fad2 genes, which is the largest fad2 gene family reported to date. 27115614 0 117 theme Transcriptome 13:25 arg1 Analysis 27:34 Genome-Scale Transcriptome Analysis 0:34 Genome-Scale Transcriptome Analysis of the Desert Shrub Artemisia sphaerocephala. 0:80 Genome-Scale Transcriptome Analysis of the Desert Shrub Artemisia sphaerocephala. 27115614 1 118 theme semi-stable 246:256 arg1 dunes 263:267 moving and semi-stable sand dunes 235:267 moving and semi-stable sand dunes 235:267 BACKGROUND Artemisia sphaerocephala, a semi-shrub belonging to the Artemisia genus of the Compositae family, is an important pioneer plant that inhabits moving and semi-stable sand dunes in the deserts and steppes of northwest and north-central China. 26617670 9 0 theme polymerization 1741:1754 arg1 degree 1731:1736 higher degree 1724:1736 higher degree of polymerization (DP) 1724:1759 Oligosaccharides with higher degree of polymerization (DP) were recalcitrant towards commercial enzyme mixtures [Ctec2, Htec2 and Multifect pectinase (MP)] compared to lower DP oligosaccharides. 26617670 2 1 from hydrolysate 479:489 arg1 polysaccharides 516:530 the total polysaccharides 506:530 the total polysaccharides in the inlet biomass (untreated), equivalent to a yield loss of about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated) 506:671 Recalcitrant oligosaccharides in AFEX-pretreated corn stover hydrolysate accumulate to the extent of about 18-25 % of the total soluble sugars in the hydrolysate and 12-18 % of the total polysaccharides in the inlet biomass (untreated), equivalent to a yield loss of about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated). 26617670 2 1 from hydrolysate 479:489 arg1 sugars 465:470 the total soluble sugars 447:470 the total soluble sugars in the hydrolysate 447:489 Recalcitrant oligosaccharides in AFEX-pretreated corn stover hydrolysate accumulate to the extent of about 18-25 % of the total soluble sugars in the hydrolysate and 12-18 % of the total polysaccharides in the inlet biomass (untreated), equivalent to a yield loss of about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated). 26617670 2 1 from hydrolysate 479:489 arg1 % 442:442 about 18-25 % 430:442 about 18-25 % of the total soluble sugars in the hydrolysate 430:489 Recalcitrant oligosaccharides in AFEX-pretreated corn stover hydrolysate accumulate to the extent of about 18-25 % of the total soluble sugars in the hydrolysate and 12-18 % of the total polysaccharides in the inlet biomass (untreated), equivalent to a yield loss of about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated). 26617670 2 1 from hydrolysate 479:489 arg1 % 501:501 12-18 % 495:501 12-18 % of the total polysaccharides in the inlet biomass (untreated), equivalent to a yield loss of about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated) 495:671 Recalcitrant oligosaccharides in AFEX-pretreated corn stover hydrolysate accumulate to the extent of about 18-25 % of the total soluble sugars in the hydrolysate and 12-18 % of the total polysaccharides in the inlet biomass (untreated), equivalent to a yield loss of about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated). 26617670 6 2 theme enzyme 1162:1167 arg1 study 1180:1184 enzyme inhibition study 1162:1184 enzyme inhibition study 1162:1184 Composition analysis, recalcitrance study and enzyme inhibition study were performed to understand their chemical nature. 26617670 1 3 theme cellulosic 305:314 arg1 biorefinery 316:326 a cellulosic biorefinery 303:326 a cellulosic biorefinery 303:326 BACKGROUND Accumulation of recalcitrant oligosaccharides during high-solids loading enzymatic hydrolysis of cellulosic biomass reduces biofuel yields and increases processing costs for a cellulosic biorefinery. 26617670 14 4 theme higher 2680:2685 arg1 yields 2695:2700 higher biofuel yields 2680:2700 higher biofuel yields with less enzyme 2680:2717 Such studies clarify the reasons for oligosaccharide accumulation and contribute to strategies by which oligosaccharides can be converted into fermentable sugars and provide higher biofuel yields with less enzyme. 26617670 9 5 with Oligosaccharides 1702:1717 arg1 degree 1731:1736 higher degree 1724:1736 higher degree of polymerization (DP) 1724:1759 Oligosaccharides with higher degree of polymerization (DP) were recalcitrant towards commercial enzyme mixtures [Ctec2, Htec2 and Multifect pectinase (MP)] compared to lower DP oligosaccharides. 26617670 7 6 theme stover 1337:1342 arg1 hydrolysis 1318:1327 high solid loading enzymatic hydrolysis 1289:1327 high solid loading enzymatic hydrolysis of corn stover (CS) irrespective of using different pretreated corn stover (dilute acid: DA, ionic liquids: IL, and ammonia fibre expansion: AFEX) 1289:1474 RESULTS Oligosaccharide accumulation occurs during high solid loading enzymatic hydrolysis of corn stover (CS) irrespective of using different pretreated corn stover (dilute acid: DA, ionic liquids: IL, and ammonia fibre expansion: AFEX). 26617670 11 7 theme oligosaccharides 2123:2138 arg1 effects 2112:2118 the inhibitory effects 2097:2118 the inhibitory effects of oligosaccharides on commercial enzymes 2097:2160 Addition of monomeric sugars to oligosaccharides increases the inhibitory effects of oligosaccharides on commercial enzymes. 26617670 3 8 theme commercial 737:746 arg1 enzymes 759:765 commercial hydrolytic enzymes 737:765 commercial hydrolytic enzymes 737:765 These oligosaccharides represent a yield loss and also inhibit commercial hydrolytic enzymes, with both being serious bottlenecks for economical biofuel production from cellulosic biomass. 26617670 14 9 theme oligosaccharide 2543:2557 arg1 accumulation 2559:2570 oligosaccharide accumulation 2543:2570 oligosaccharide accumulation 2543:2570 Such studies clarify the reasons for oligosaccharide accumulation and contribute to strategies by which oligosaccharides can be converted into fermentable sugars and provide higher biofuel yields with less enzyme. 26617670 2 10 theme Recalcitrant 329:340 arg1 oligosaccharides 342:357 Recalcitrant oligosaccharides 329:357 Recalcitrant oligosaccharides in AFEX-pretreated corn stover hydrolysate 329:400 Recalcitrant oligosaccharides in AFEX-pretreated corn stover hydrolysate accumulate to the extent of about 18-25 % of the total soluble sugars in the hydrolysate and 12-18 % of the total polysaccharides in the inlet biomass (untreated), equivalent to a yield loss of about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated). 26617670 14 11 theme fermentable 2649:2659 arg1 sugars 2661:2666 fermentable sugars 2649:2666 fermentable sugars 2649:2666 Such studies clarify the reasons for oligosaccharide accumulation and contribute to strategies by which oligosaccharides can be converted into fermentable sugars and provide higher biofuel yields with less enzyme. 26617670 2 12 theme dry 649:651 arg1 biomass 653:659 inlet dry biomass 643:659 inlet dry biomass (untreated) 643:671 Recalcitrant oligosaccharides in AFEX-pretreated corn stover hydrolysate accumulate to the extent of about 18-25 % of the total soluble sugars in the hydrolysate and 12-18 % of the total polysaccharides in the inlet biomass (untreated), equivalent to a yield loss of about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated). 26617670 10 13 dep substrates 1939:1948 arg1 xylan 1962:1966 xylan 1962:1966 xylan 1962:1966 Enzyme inhibition studies using processed substrates (Avicel and xylan) showed that low DP oligosaccharides also inhibit commercial enzymes. 26617670 10 13 dep substrates 1939:1948 arg1 Avicel 1951:1956 Avicel 1951:1956 Avicel 1951:1956 Enzyme inhibition studies using processed substrates (Avicel and xylan) showed that low DP oligosaccharides also inhibit commercial enzymes. 26617670 10 13 dep substrates 1939:1948 arg1 substrates 1939:1948 processed substrates 1929:1948 processed substrates (Avicel and xylan) 1929:1967 Enzyme inhibition studies using processed substrates (Avicel and xylan) showed that low DP oligosaccharides also inhibit commercial enzymes. 26617670 5 14 from hydrolysate 1082:1092 arg1 oligosaccharides 1041:1056 recalcitrant oligosaccharides 1028:1056 recalcitrant oligosaccharides from high solid loading hydrolysate 1028:1092 This work presents a robust method for separating recalcitrant oligosaccharides from high solid loading hydrolysate in gramme quantities. 26617670 1 15 theme biomass 237:243 arg1 hydrolysis 212:221 high-solids loading enzymatic hydrolysis 182:221 high-solids loading enzymatic hydrolysis of cellulosic biomass 182:243 BACKGROUND Accumulation of recalcitrant oligosaccharides during high-solids loading enzymatic hydrolysis of cellulosic biomass reduces biofuel yields and increases processing costs for a cellulosic biorefinery. 26617670 4 16 theme commercial 958:967 arg1 enzymes 969:975 commercial enzymes 958:975 commercial enzymes 958:975 Very little is understood about the nature of these oligomers and why they are recalcitrant to commercial enzymes. 26617670 2 17 from % 442:442 arg1 hydrolysate 479:489 the hydrolysate 475:489 the hydrolysate 475:489 Recalcitrant oligosaccharides in AFEX-pretreated corn stover hydrolysate accumulate to the extent of about 18-25 % of the total soluble sugars in the hydrolysate and 12-18 % of the total polysaccharides in the inlet biomass (untreated), equivalent to a yield loss of about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated). 26617670 2 17 from % 442:442 arg1 biomass 545:551 the inlet biomass 535:551 the inlet biomass (untreated) 535:563 Recalcitrant oligosaccharides in AFEX-pretreated corn stover hydrolysate accumulate to the extent of about 18-25 % of the total soluble sugars in the hydrolysate and 12-18 % of the total polysaccharides in the inlet biomass (untreated), equivalent to a yield loss of about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated). 26617670 7 18 theme fibre 1453:1457 arg1 liquids 1428:1434 ionic liquids 1422:1434 ionic liquids: IL, and ammonia fibre expansion 1422:1467 RESULTS Oligosaccharide accumulation occurs during high solid loading enzymatic hydrolysis of corn stover (CS) irrespective of using different pretreated corn stover (dilute acid: DA, ionic liquids: IL, and ammonia fibre expansion: AFEX). 26617670 7 18 theme fibre 1453:1457 arg1 expansion 1459:1467 ammonia fibre expansion 1445:1467 ammonia fibre expansion 1445:1467 RESULTS Oligosaccharide accumulation occurs during high solid loading enzymatic hydrolysis of corn stover (CS) irrespective of using different pretreated corn stover (dilute acid: DA, ionic liquids: IL, and ammonia fibre expansion: AFEX). 26617670 2 19 theme corn 378:381 arg1 hydrolysate 390:400 AFEX-pretreated corn stover hydrolysate 362:400 AFEX-pretreated corn stover hydrolysate 362:400 Recalcitrant oligosaccharides in AFEX-pretreated corn stover hydrolysate accumulate to the extent of about 18-25 % of the total soluble sugars in the hydrolysate and 12-18 % of the total polysaccharides in the inlet biomass (untreated), equivalent to a yield loss of about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated). 26617670 1 20 theme biofuel 253:259 arg1 yields 261:266 biofuel yields 253:266 biofuel yields 253:266 BACKGROUND Accumulation of recalcitrant oligosaccharides during high-solids loading enzymatic hydrolysis of cellulosic biomass reduces biofuel yields and increases processing costs for a cellulosic biorefinery. 26617670 2 21 theme yield 582:586 arg1 loss 588:591 a yield loss 580:591 a yield loss of about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated) 580:671 Recalcitrant oligosaccharides in AFEX-pretreated corn stover hydrolysate accumulate to the extent of about 18-25 % of the total soluble sugars in the hydrolysate and 12-18 % of the total polysaccharides in the inlet biomass (untreated), equivalent to a yield loss of about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated). 26617670 12 22 theme DP 2261:2262 arg1 oligomers 2264:2272 different DP oligomers 2251:2272 different DP oligomers 2251:2272 CONCLUSION The carbohydrate composition of the recalcitrant oligosaccharides, ratios of different DP oligomers and their distribution profiles were determined. 26617670 3 23 theme economical 808:817 arg1 production 827:836 economical biofuel production 808:836 economical biofuel production from cellulosic biomass 808:860 These oligosaccharides represent a yield loss and also inhibit commercial hydrolytic enzymes, with both being serious bottlenecks for economical biofuel production from cellulosic biomass. 26617670 7 24 theme RESULTS 1238:1244 arg1 accumulation 1262:1273 RESULTS Oligosaccharide accumulation 1238:1273 RESULTS Oligosaccharide accumulation 1238:1273 RESULTS Oligosaccharide accumulation occurs during high solid loading enzymatic hydrolysis of corn stover (CS) irrespective of using different pretreated corn stover (dilute acid: DA, ionic liquids: IL, and ammonia fibre expansion: AFEX). 26617670 2 25 theme monomeric 612:620 arg1 sugars 622:627 monomeric sugars 612:627 monomeric sugars per 100 kg of inlet dry biomass (untreated) 612:671 Recalcitrant oligosaccharides in AFEX-pretreated corn stover hydrolysate accumulate to the extent of about 18-25 % of the total soluble sugars in the hydrolysate and 12-18 % of the total polysaccharides in the inlet biomass (untreated), equivalent to a yield loss of about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated). 26617670 9 26 theme Multifect 1832:1840 arg1 mixtures 1805:1812 commercial enzyme mixtures [Ctec2, Htec2 and Multifect pectinase (MP)] 1787:1856 commercial enzyme mixtures [Ctec2, Htec2 and Multifect pectinase (MP)] 1787:1856 Oligosaccharides with higher degree of polymerization (DP) were recalcitrant towards commercial enzyme mixtures [Ctec2, Htec2 and Multifect pectinase (MP)] compared to lower DP oligosaccharides. 26617670 9 26 theme Multifect 1832:1840 arg1 MP 1853:1854 MP 1853:1854 MP 1853:1854 Oligosaccharides with higher degree of polymerization (DP) were recalcitrant towards commercial enzyme mixtures [Ctec2, Htec2 and Multifect pectinase (MP)] compared to lower DP oligosaccharides. 26617670 9 26 theme Multifect 1832:1840 arg1 pectinase 1842:1850 Multifect pectinase 1832:1850 Multifect pectinase (MP) 1832:1855 Oligosaccharides with higher degree of polymerization (DP) were recalcitrant towards commercial enzyme mixtures [Ctec2, Htec2 and Multifect pectinase (MP)] compared to lower DP oligosaccharides. 26617670 12 27 theme recalcitrant 2210:2221 arg1 oligosaccharides 2223:2238 the recalcitrant oligosaccharides 2206:2238 the recalcitrant oligosaccharides 2206:2238 CONCLUSION The carbohydrate composition of the recalcitrant oligosaccharides, ratios of different DP oligomers and their distribution profiles were determined. 26617670 5 28 theme gramme 1097:1102 arg1 quantities 1104:1113 gramme quantities 1097:1113 gramme quantities 1097:1113 This work presents a robust method for separating recalcitrant oligosaccharides from high solid loading hydrolysate in gramme quantities. 26617670 11 29 theme monomeric 2050:2058 arg1 sugars 2060:2065 monomeric sugars 2050:2065 monomeric sugars 2050:2065 Addition of monomeric sugars to oligosaccharides increases the inhibitory effects of oligosaccharides on commercial enzymes. 26617670 2 30 from oligosaccharides 342:357 arg1 hydrolysate 390:400 AFEX-pretreated corn stover hydrolysate 362:400 AFEX-pretreated corn stover hydrolysate 362:400 Recalcitrant oligosaccharides in AFEX-pretreated corn stover hydrolysate accumulate to the extent of about 18-25 % of the total soluble sugars in the hydrolysate and 12-18 % of the total polysaccharides in the inlet biomass (untreated), equivalent to a yield loss of about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated). 26617670 2 31 theme 7-9 kg 602:607 arg1 loss 588:591 a yield loss 580:591 a yield loss of about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated) 580:671 Recalcitrant oligosaccharides in AFEX-pretreated corn stover hydrolysate accumulate to the extent of about 18-25 % of the total soluble sugars in the hydrolysate and 12-18 % of the total polysaccharides in the inlet biomass (untreated), equivalent to a yield loss of about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated). 26617670 8 32 theme recalcitrant 1523:1534 arg1 oligosaccharides 1536:1551 recalcitrant oligosaccharides 1523:1551 recalcitrant oligosaccharides 1523:1551 The methodology for large-scale separation of recalcitrant oligosaccharides from 25 % solids-loading AFEX-corn stover hydrolysate using charcoal fractionation and size exclusion chromatography is reported for the first time. 26617670 3 33 theme cellulosic 843:852 arg1 biomass 854:860 cellulosic biomass 843:860 cellulosic biomass 843:860 These oligosaccharides represent a yield loss and also inhibit commercial hydrolytic enzymes, with both being serious bottlenecks for economical biofuel production from cellulosic biomass. 26617670 10 34 theme processed 1929:1937 arg1 xylan 1962:1966 xylan 1962:1966 xylan 1962:1966 Enzyme inhibition studies using processed substrates (Avicel and xylan) showed that low DP oligosaccharides also inhibit commercial enzymes. 26617670 10 34 theme processed 1929:1937 arg1 Avicel 1951:1956 Avicel 1951:1956 Avicel 1951:1956 Enzyme inhibition studies using processed substrates (Avicel and xylan) showed that low DP oligosaccharides also inhibit commercial enzymes. 26617670 10 34 theme processed 1929:1937 arg1 substrates 1939:1948 processed substrates 1929:1948 processed substrates (Avicel and xylan) 1929:1967 Enzyme inhibition studies using processed substrates (Avicel and xylan) showed that low DP oligosaccharides also inhibit commercial enzymes. 26617670 1 35 theme oligosaccharides 158:173 arg1 Accumulation 129:140 BACKGROUND Accumulation 118:140 BACKGROUND Accumulation of recalcitrant oligosaccharides during high-solids loading enzymatic hydrolysis of cellulosic biomass 118:243 BACKGROUND Accumulation of recalcitrant oligosaccharides during high-solids loading enzymatic hydrolysis of cellulosic biomass reduces biofuel yields and increases processing costs for a cellulosic biorefinery. 26617670 12 36 theme carbohydrate 2178:2189 arg1 composition 2191:2201 The carbohydrate composition 2174:2201 The carbohydrate composition of the recalcitrant oligosaccharides, ratios of different DP oligomers and their distribution profiles 2174:2304 CONCLUSION The carbohydrate composition of the recalcitrant oligosaccharides, ratios of different DP oligomers and their distribution profiles were determined. 26617670 7 37 theme corn 1332:1335 arg1 CS 1345:1346 CS 1345:1346 CS 1345:1346 RESULTS Oligosaccharide accumulation occurs during high solid loading enzymatic hydrolysis of corn stover (CS) irrespective of using different pretreated corn stover (dilute acid: DA, ionic liquids: IL, and ammonia fibre expansion: AFEX). 26617670 7 37 theme corn 1332:1335 arg1 stover 1337:1342 corn stover 1332:1342 corn stover (CS) irrespective of using different pretreated corn stover (dilute acid: DA, ionic liquids: IL, and ammonia fibre expansion: AFEX) 1332:1474 RESULTS Oligosaccharide accumulation occurs during high solid loading enzymatic hydrolysis of corn stover (CS) irrespective of using different pretreated corn stover (dilute acid: DA, ionic liquids: IL, and ammonia fibre expansion: AFEX). 26617670 1 38 theme high-solids 182:192 arg1 hydrolysis 212:221 high-solids loading enzymatic hydrolysis 182:221 high-solids loading enzymatic hydrolysis of cellulosic biomass 182:243 BACKGROUND Accumulation of recalcitrant oligosaccharides during high-solids loading enzymatic hydrolysis of cellulosic biomass reduces biofuel yields and increases processing costs for a cellulosic biorefinery. 26617670 8 39 theme % 1561:1561 arg1 hydrolysate 1595:1605 25 % solids-loading AFEX-corn stover hydrolysate 1558:1605 25 % solids-loading AFEX-corn stover hydrolysate using charcoal fractionation and size exclusion chromatography 1558:1668 The methodology for large-scale separation of recalcitrant oligosaccharides from 25 % solids-loading AFEX-corn stover hydrolysate using charcoal fractionation and size exclusion chromatography is reported for the first time. 26617670 0 40 theme high 76:79 arg1 hydrolysis 106:115 high solids-loading enzymatic hydrolysis 76:115 high solids-loading enzymatic hydrolysis 76:115 Sugar loss and enzyme inhibition due to oligosaccharide accumulation during high solids-loading enzymatic hydrolysis. 26617670 1 41 theme enzymatic 202:210 arg1 hydrolysis 212:221 high-solids loading enzymatic hydrolysis 182:221 high-solids loading enzymatic hydrolysis of cellulosic biomass 182:243 BACKGROUND Accumulation of recalcitrant oligosaccharides during high-solids loading enzymatic hydrolysis of cellulosic biomass reduces biofuel yields and increases processing costs for a cellulosic biorefinery. 26617670 8 42 theme AFEX-corn 1578:1586 arg1 hydrolysate 1595:1605 25 % solids-loading AFEX-corn stover hydrolysate 1558:1605 25 % solids-loading AFEX-corn stover hydrolysate using charcoal fractionation and size exclusion chromatography 1558:1668 The methodology for large-scale separation of recalcitrant oligosaccharides from 25 % solids-loading AFEX-corn stover hydrolysate using charcoal fractionation and size exclusion chromatography is reported for the first time. 26617670 0 43 theme enzymatic 96:104 arg1 hydrolysis 106:115 high solids-loading enzymatic hydrolysis 76:115 high solids-loading enzymatic hydrolysis 76:115 Sugar loss and enzyme inhibition due to oligosaccharide accumulation during high solids-loading enzymatic hydrolysis. 26617670 9 44 theme lower 1870:1874 arg1 oligosaccharides 1879:1894 lower DP oligosaccharides 1870:1894 lower DP oligosaccharides 1870:1894 Oligosaccharides with higher degree of polymerization (DP) were recalcitrant towards commercial enzyme mixtures [Ctec2, Htec2 and Multifect pectinase (MP)] compared to lower DP oligosaccharides. 26617670 14 45 theme Such 2506:2509 arg1 studies 2511:2517 Such studies 2506:2517 Such studies 2506:2517 Such studies clarify the reasons for oligosaccharide accumulation and contribute to strategies by which oligosaccharides can be converted into fermentable sugars and provide higher biofuel yields with less enzyme. 26617670 2 46 theme sugars 465:470 arg1 polysaccharides 516:530 the total polysaccharides 506:530 the total polysaccharides in the inlet biomass (untreated), equivalent to a yield loss of about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated) 506:671 Recalcitrant oligosaccharides in AFEX-pretreated corn stover hydrolysate accumulate to the extent of about 18-25 % of the total soluble sugars in the hydrolysate and 12-18 % of the total polysaccharides in the inlet biomass (untreated), equivalent to a yield loss of about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated). 26617670 2 46 theme sugars 465:470 arg1 sugars 465:470 the total soluble sugars 447:470 the total soluble sugars in the hydrolysate 447:489 Recalcitrant oligosaccharides in AFEX-pretreated corn stover hydrolysate accumulate to the extent of about 18-25 % of the total soluble sugars in the hydrolysate and 12-18 % of the total polysaccharides in the inlet biomass (untreated), equivalent to a yield loss of about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated). 26617670 2 46 theme sugars 465:470 arg1 % 442:442 about 18-25 % 430:442 about 18-25 % of the total soluble sugars in the hydrolysate 430:489 Recalcitrant oligosaccharides in AFEX-pretreated corn stover hydrolysate accumulate to the extent of about 18-25 % of the total soluble sugars in the hydrolysate and 12-18 % of the total polysaccharides in the inlet biomass (untreated), equivalent to a yield loss of about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated). 26617670 2 46 theme sugars 465:470 arg1 % 501:501 12-18 % 495:501 12-18 % of the total polysaccharides in the inlet biomass (untreated), equivalent to a yield loss of about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated) 495:671 Recalcitrant oligosaccharides in AFEX-pretreated corn stover hydrolysate accumulate to the extent of about 18-25 % of the total soluble sugars in the hydrolysate and 12-18 % of the total polysaccharides in the inlet biomass (untreated), equivalent to a yield loss of about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated). 26617670 7 47 theme high 1289:1292 arg1 hydrolysis 1318:1327 high solid loading enzymatic hydrolysis 1289:1327 high solid loading enzymatic hydrolysis of corn stover (CS) irrespective of using different pretreated corn stover (dilute acid: DA, ionic liquids: IL, and ammonia fibre expansion: AFEX) 1289:1474 RESULTS Oligosaccharide accumulation occurs during high solid loading enzymatic hydrolysis of corn stover (CS) irrespective of using different pretreated corn stover (dilute acid: DA, ionic liquids: IL, and ammonia fibre expansion: AFEX). 26617670 6 48 theme recalcitrance 1138:1150 arg1 study 1152:1156 recalcitrance study 1138:1156 recalcitrance study 1138:1156 Composition analysis, recalcitrance study and enzyme inhibition study were performed to understand their chemical nature. 26617670 8 49 theme charcoal 1613:1620 arg1 fractionation 1622:1634 charcoal fractionation and size exclusion chromatography 1613:1668 fractionation 1622:1634 The methodology for large-scale separation of recalcitrant oligosaccharides from 25 % solids-loading AFEX-corn stover hydrolysate using charcoal fractionation and size exclusion chromatography is reported for the first time. 26617670 2 50 theme total 451:455 arg1 sugars 465:470 the total soluble sugars 447:470 the total soluble sugars in the hydrolysate 447:489 Recalcitrant oligosaccharides in AFEX-pretreated corn stover hydrolysate accumulate to the extent of about 18-25 % of the total soluble sugars in the hydrolysate and 12-18 % of the total polysaccharides in the inlet biomass (untreated), equivalent to a yield loss of about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated). 26617670 0 51 theme Sugar 0:4 arg1 loss 6:9 Sugar loss 0:9 Sugar loss 0:9 Sugar loss and enzyme inhibition due to oligosaccharide accumulation during high solids-loading enzymatic hydrolysis. 26617670 2 52 theme % 501:501 arg1 extent 420:425 the extent 416:425 the extent of about 18-25 % of the total soluble sugars in the hydrolysate and 12-18 % of the total polysaccharides in the inlet biomass (untreated), equivalent to a yield loss of about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated) 416:671 Recalcitrant oligosaccharides in AFEX-pretreated corn stover hydrolysate accumulate to the extent of about 18-25 % of the total soluble sugars in the hydrolysate and 12-18 % of the total polysaccharides in the inlet biomass (untreated), equivalent to a yield loss of about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated). 26617670 7 53 theme Oligosaccharide 1246:1260 arg1 accumulation 1262:1273 RESULTS Oligosaccharide accumulation 1238:1273 RESULTS Oligosaccharide accumulation 1238:1273 RESULTS Oligosaccharide accumulation occurs during high solid loading enzymatic hydrolysis of corn stover (CS) irrespective of using different pretreated corn stover (dilute acid: DA, ionic liquids: IL, and ammonia fibre expansion: AFEX). 26617670 13 54 theme enzyme 2405:2410 arg1 mixtures 2412:2419 the commercial enzyme mixtures 2390:2419 the commercial enzyme mixtures 2390:2419 Recalcitrance and enzyme inhibition studies help determine whether the commercial enzyme mixtures lack the enzyme activities required to completely de-polymerize the plant cell wall. 26617670 1 55 theme BACKGROUND 118:127 arg1 Accumulation 129:140 BACKGROUND Accumulation 118:140 BACKGROUND Accumulation of recalcitrant oligosaccharides during high-solids loading enzymatic hydrolysis of cellulosic biomass 118:243 BACKGROUND Accumulation of recalcitrant oligosaccharides during high-solids loading enzymatic hydrolysis of cellulosic biomass reduces biofuel yields and increases processing costs for a cellulosic biorefinery. 26617670 8 56 theme exclusion 1645:1653 arg1 chromatography 1655:1668 charcoal fractionation and size exclusion chromatography 1613:1668 chromatography 1655:1668 The methodology for large-scale separation of recalcitrant oligosaccharides from 25 % solids-loading AFEX-corn stover hydrolysate using charcoal fractionation and size exclusion chromatography is reported for the first time. 26617670 5 57 theme loading 1074:1080 arg1 hydrolysate 1082:1092 high solid loading hydrolysate 1063:1092 high solid loading hydrolysate 1063:1092 This work presents a robust method for separating recalcitrant oligosaccharides from high solid loading hydrolysate in gramme quantities. 26617670 7 58 theme corn 1392:1395 arg1 stover 1397:1402 different pretreated corn stover 1371:1402 different pretreated corn stover (dilute acid: DA, ionic liquids: IL, and ammonia fibre expansion: AFEX) 1371:1474 RESULTS Oligosaccharide accumulation occurs during high solid loading enzymatic hydrolysis of corn stover (CS) irrespective of using different pretreated corn stover (dilute acid: DA, ionic liquids: IL, and ammonia fibre expansion: AFEX). 26617670 7 58 theme corn 1392:1395 arg1 acid 1412:1415 dilute acid 1405:1415 dilute acid 1405:1415 RESULTS Oligosaccharide accumulation occurs during high solid loading enzymatic hydrolysis of corn stover (CS) irrespective of using different pretreated corn stover (dilute acid: DA, ionic liquids: IL, and ammonia fibre expansion: AFEX). 26617670 2 59 theme polysaccharides 516:530 arg1 polysaccharides 516:530 the total polysaccharides 506:530 the total polysaccharides in the inlet biomass (untreated), equivalent to a yield loss of about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated) 506:671 Recalcitrant oligosaccharides in AFEX-pretreated corn stover hydrolysate accumulate to the extent of about 18-25 % of the total soluble sugars in the hydrolysate and 12-18 % of the total polysaccharides in the inlet biomass (untreated), equivalent to a yield loss of about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated). 26617670 2 59 theme polysaccharides 516:530 arg1 sugars 465:470 the total soluble sugars 447:470 the total soluble sugars in the hydrolysate 447:489 Recalcitrant oligosaccharides in AFEX-pretreated corn stover hydrolysate accumulate to the extent of about 18-25 % of the total soluble sugars in the hydrolysate and 12-18 % of the total polysaccharides in the inlet biomass (untreated), equivalent to a yield loss of about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated). 26617670 2 59 theme polysaccharides 516:530 arg1 % 442:442 about 18-25 % 430:442 about 18-25 % of the total soluble sugars in the hydrolysate 430:489 Recalcitrant oligosaccharides in AFEX-pretreated corn stover hydrolysate accumulate to the extent of about 18-25 % of the total soluble sugars in the hydrolysate and 12-18 % of the total polysaccharides in the inlet biomass (untreated), equivalent to a yield loss of about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated). 26617670 2 59 theme polysaccharides 516:530 arg1 % 501:501 12-18 % 495:501 12-18 % of the total polysaccharides in the inlet biomass (untreated), equivalent to a yield loss of about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated) 495:671 Recalcitrant oligosaccharides in AFEX-pretreated corn stover hydrolysate accumulate to the extent of about 18-25 % of the total soluble sugars in the hydrolysate and 12-18 % of the total polysaccharides in the inlet biomass (untreated), equivalent to a yield loss of about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated). 26617670 12 60 dep CONCLUSION 2163:2172 arg1 determined 2311:2320 determined 2311:2320 were determined 2306:2320 CONCLUSION The carbohydrate composition of the recalcitrant oligosaccharides, ratios of different DP oligomers and their distribution profiles were determined. 26617670 8 61 from hydrolysate 1595:1605 arg1 separation 1509:1518 large-scale separation 1497:1518 large-scale separation of recalcitrant oligosaccharides from 25 % solids-loading AFEX-corn stover hydrolysate using charcoal fractionation and size exclusion chromatography 1497:1668 The methodology for large-scale separation of recalcitrant oligosaccharides from 25 % solids-loading AFEX-corn stover hydrolysate using charcoal fractionation and size exclusion chromatography is reported for the first time. 26617670 8 62 theme solids-loading 1563:1576 arg1 hydrolysate 1595:1605 25 % solids-loading AFEX-corn stover hydrolysate 1558:1605 25 % solids-loading AFEX-corn stover hydrolysate using charcoal fractionation and size exclusion chromatography 1558:1668 The methodology for large-scale separation of recalcitrant oligosaccharides from 25 % solids-loading AFEX-corn stover hydrolysate using charcoal fractionation and size exclusion chromatography is reported for the first time. 26617670 2 63 from sugars 465:470 arg1 hydrolysate 479:489 the hydrolysate 475:489 the hydrolysate 475:489 Recalcitrant oligosaccharides in AFEX-pretreated corn stover hydrolysate accumulate to the extent of about 18-25 % of the total soluble sugars in the hydrolysate and 12-18 % of the total polysaccharides in the inlet biomass (untreated), equivalent to a yield loss of about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated). 26617670 7 64 theme different 1371:1379 arg1 stover 1397:1402 different pretreated corn stover 1371:1402 different pretreated corn stover (dilute acid: DA, ionic liquids: IL, and ammonia fibre expansion: AFEX) 1371:1474 RESULTS Oligosaccharide accumulation occurs during high solid loading enzymatic hydrolysis of corn stover (CS) irrespective of using different pretreated corn stover (dilute acid: DA, ionic liquids: IL, and ammonia fibre expansion: AFEX). 26617670 7 64 theme different 1371:1379 arg1 acid 1412:1415 dilute acid 1405:1415 dilute acid 1405:1415 RESULTS Oligosaccharide accumulation occurs during high solid loading enzymatic hydrolysis of corn stover (CS) irrespective of using different pretreated corn stover (dilute acid: DA, ionic liquids: IL, and ammonia fibre expansion: AFEX). 26617670 3 65 theme yield 709:713 arg1 loss 715:718 a yield loss 707:718 a yield loss 707:718 These oligosaccharides represent a yield loss and also inhibit commercial hydrolytic enzymes, with both being serious bottlenecks for economical biofuel production from cellulosic biomass. 26617670 7 66 dep acid 1412:1415 arg1 liquids 1428:1434 ionic liquids 1422:1434 ionic liquids: IL, and ammonia fibre expansion 1422:1467 RESULTS Oligosaccharide accumulation occurs during high solid loading enzymatic hydrolysis of corn stover (CS) irrespective of using different pretreated corn stover (dilute acid: DA, ionic liquids: IL, and ammonia fibre expansion: AFEX). 26617670 7 66 dep acid 1412:1415 arg1 AFEX 1470:1473 AFEX 1470:1473 AFEX 1470:1473 RESULTS Oligosaccharide accumulation occurs during high solid loading enzymatic hydrolysis of corn stover (CS) irrespective of using different pretreated corn stover (dilute acid: DA, ionic liquids: IL, and ammonia fibre expansion: AFEX). 26617670 7 66 dep acid 1412:1415 arg1 expansion 1459:1467 ammonia fibre expansion 1445:1467 ammonia fibre expansion 1445:1467 RESULTS Oligosaccharide accumulation occurs during high solid loading enzymatic hydrolysis of corn stover (CS) irrespective of using different pretreated corn stover (dilute acid: DA, ionic liquids: IL, and ammonia fibre expansion: AFEX). 26617670 7 66 dep acid 1412:1415 arg1 IL 1437:1438 IL 1437:1438 IL 1437:1438 RESULTS Oligosaccharide accumulation occurs during high solid loading enzymatic hydrolysis of corn stover (CS) irrespective of using different pretreated corn stover (dilute acid: DA, ionic liquids: IL, and ammonia fibre expansion: AFEX). 26617670 7 66 dep acid 1412:1415 arg1 DA 1418:1419 DA 1418:1419 DA 1418:1419 RESULTS Oligosaccharide accumulation occurs during high solid loading enzymatic hydrolysis of corn stover (CS) irrespective of using different pretreated corn stover (dilute acid: DA, ionic liquids: IL, and ammonia fibre expansion: AFEX). 26617670 9 67 theme higher 1724:1729 arg1 degree 1731:1736 higher degree 1724:1736 higher degree of polymerization (DP) 1724:1759 Oligosaccharides with higher degree of polymerization (DP) were recalcitrant towards commercial enzyme mixtures [Ctec2, Htec2 and Multifect pectinase (MP)] compared to lower DP oligosaccharides. 26617670 8 68 theme first 1690:1694 arg1 time 1696:1699 the first time 1686:1699 the first time 1686:1699 The methodology for large-scale separation of recalcitrant oligosaccharides from 25 % solids-loading AFEX-corn stover hydrolysate using charcoal fractionation and size exclusion chromatography is reported for the first time. 26617670 13 69 theme enzyme 2341:2346 arg1 studies 2359:2365 enzyme inhibition studies 2341:2365 enzyme inhibition studies 2341:2365 Recalcitrance and enzyme inhibition studies help determine whether the commercial enzyme mixtures lack the enzyme activities required to completely de-polymerize the plant cell wall. 26617670 5 70 theme high 1063:1066 arg1 hydrolysate 1082:1092 high solid loading hydrolysate 1063:1092 high solid loading hydrolysate 1063:1092 This work presents a robust method for separating recalcitrant oligosaccharides from high solid loading hydrolysate in gramme quantities. 26617670 6 71 theme inhibition 1169:1178 arg1 study 1180:1184 enzyme inhibition study 1162:1184 enzyme inhibition study 1162:1184 Composition analysis, recalcitrance study and enzyme inhibition study were performed to understand their chemical nature. 26617670 11 72 from effects 2112:2118 arg1 enzymes 2154:2160 commercial enzymes 2143:2160 commercial enzymes 2143:2160 Addition of monomeric sugars to oligosaccharides increases the inhibitory effects of oligosaccharides on commercial enzymes. 26617670 7 73 theme enzymatic 1308:1316 arg1 hydrolysis 1318:1327 high solid loading enzymatic hydrolysis 1289:1327 high solid loading enzymatic hydrolysis of corn stover (CS) irrespective of using different pretreated corn stover (dilute acid: DA, ionic liquids: IL, and ammonia fibre expansion: AFEX) 1289:1474 RESULTS Oligosaccharide accumulation occurs during high solid loading enzymatic hydrolysis of corn stover (CS) irrespective of using different pretreated corn stover (dilute acid: DA, ionic liquids: IL, and ammonia fibre expansion: AFEX). 26617670 10 74 theme commercial 2018:2027 arg1 enzymes 2029:2035 commercial enzymes 2018:2035 commercial enzymes 2018:2035 Enzyme inhibition studies using processed substrates (Avicel and xylan) showed that low DP oligosaccharides also inhibit commercial enzymes. 26617670 14 75 theme biofuel 2687:2693 arg1 yields 2695:2700 higher biofuel yields 2680:2700 higher biofuel yields with less enzyme 2680:2717 Such studies clarify the reasons for oligosaccharide accumulation and contribute to strategies by which oligosaccharides can be converted into fermentable sugars and provide higher biofuel yields with less enzyme. 26617670 10 76 theme DP 1985:1986 arg1 oligosaccharides 1988:2003 low DP oligosaccharides 1981:2003 low DP oligosaccharides 1981:2003 Enzyme inhibition studies using processed substrates (Avicel and xylan) showed that low DP oligosaccharides also inhibit commercial enzymes. 26617670 2 77 theme AFEX-pretreated 362:376 arg1 hydrolysate 390:400 AFEX-pretreated corn stover hydrolysate 362:400 AFEX-pretreated corn stover hydrolysate 362:400 Recalcitrant oligosaccharides in AFEX-pretreated corn stover hydrolysate accumulate to the extent of about 18-25 % of the total soluble sugars in the hydrolysate and 12-18 % of the total polysaccharides in the inlet biomass (untreated), equivalent to a yield loss of about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated). 26617670 2 78 theme sugars 622:627 arg1 7-9 kg 602:607 about 7-9 kg 596:607 about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated) 596:671 Recalcitrant oligosaccharides in AFEX-pretreated corn stover hydrolysate accumulate to the extent of about 18-25 % of the total soluble sugars in the hydrolysate and 12-18 % of the total polysaccharides in the inlet biomass (untreated), equivalent to a yield loss of about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated). 26617670 13 79 theme enzyme 2430:2435 arg1 activities 2437:2446 the enzyme activities 2426:2446 the enzyme activities required to completely de-polymerize the plant cell wall 2426:2503 Recalcitrance and enzyme inhibition studies help determine whether the commercial enzyme mixtures lack the enzyme activities required to completely de-polymerize the plant cell wall. 26617670 12 80 theme distribution 2284:2295 arg1 profiles 2297:2304 their distribution profiles 2278:2304 their distribution profiles 2278:2304 CONCLUSION The carbohydrate composition of the recalcitrant oligosaccharides, ratios of different DP oligomers and their distribution profiles were determined. 26617670 2 81 theme biomass 653:659 arg1 100 kg 633:638 100 kg 633:638 100 kg of inlet dry biomass (untreated) 633:671 Recalcitrant oligosaccharides in AFEX-pretreated corn stover hydrolysate accumulate to the extent of about 18-25 % of the total soluble sugars in the hydrolysate and 12-18 % of the total polysaccharides in the inlet biomass (untreated), equivalent to a yield loss of about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated). 26617670 12 82 theme oligomers 2264:2272 arg1 ratios 2241:2246 ratios 2241:2246 ratios of different DP oligomers 2241:2272 CONCLUSION The carbohydrate composition of the recalcitrant oligosaccharides, ratios of different DP oligomers and their distribution profiles were determined. 26617670 12 82 theme oligomers 2264:2272 arg1 oligosaccharides 2223:2238 the recalcitrant oligosaccharides 2206:2238 the recalcitrant oligosaccharides 2206:2238 CONCLUSION The carbohydrate composition of the recalcitrant oligosaccharides, ratios of different DP oligomers and their distribution profiles were determined. 26617670 12 82 theme oligomers 2264:2272 arg1 profiles 2297:2304 their distribution profiles 2278:2304 their distribution profiles 2278:2304 CONCLUSION The carbohydrate composition of the recalcitrant oligosaccharides, ratios of different DP oligomers and their distribution profiles were determined. 26617670 3 83 theme hydrolytic 748:757 arg1 enzymes 759:765 commercial hydrolytic enzymes 737:765 commercial hydrolytic enzymes 737:765 These oligosaccharides represent a yield loss and also inhibit commercial hydrolytic enzymes, with both being serious bottlenecks for economical biofuel production from cellulosic biomass. 26617670 1 84 theme cellulosic 226:235 arg1 biomass 237:243 cellulosic biomass 226:243 cellulosic biomass 226:243 BACKGROUND Accumulation of recalcitrant oligosaccharides during high-solids loading enzymatic hydrolysis of cellulosic biomass reduces biofuel yields and increases processing costs for a cellulosic biorefinery. 26617670 2 85 theme inlet 643:647 arg1 biomass 653:659 inlet dry biomass 643:659 inlet dry biomass (untreated) 643:671 Recalcitrant oligosaccharides in AFEX-pretreated corn stover hydrolysate accumulate to the extent of about 18-25 % of the total soluble sugars in the hydrolysate and 12-18 % of the total polysaccharides in the inlet biomass (untreated), equivalent to a yield loss of about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated). 26617670 3 86 theme serious 784:790 arg1 bottlenecks 792:802 serious bottlenecks 784:802 serious bottlenecks 784:802 These oligosaccharides represent a yield loss and also inhibit commercial hydrolytic enzymes, with both being serious bottlenecks for economical biofuel production from cellulosic biomass. 26617670 2 87 theme stover 383:388 arg1 hydrolysate 390:400 AFEX-pretreated corn stover hydrolysate 362:400 AFEX-pretreated corn stover hydrolysate 362:400 Recalcitrant oligosaccharides in AFEX-pretreated corn stover hydrolysate accumulate to the extent of about 18-25 % of the total soluble sugars in the hydrolysate and 12-18 % of the total polysaccharides in the inlet biomass (untreated), equivalent to a yield loss of about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated). 26617670 2 88 dep biomass 653:659 arg1 untreated 662:670 untreated 662:670 untreated 662:670 Recalcitrant oligosaccharides in AFEX-pretreated corn stover hydrolysate accumulate to the extent of about 18-25 % of the total soluble sugars in the hydrolysate and 12-18 % of the total polysaccharides in the inlet biomass (untreated), equivalent to a yield loss of about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated). 26617670 2 89 from biomass 545:551 arg1 polysaccharides 516:530 the total polysaccharides 506:530 the total polysaccharides in the inlet biomass (untreated), equivalent to a yield loss of about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated) 506:671 Recalcitrant oligosaccharides in AFEX-pretreated corn stover hydrolysate accumulate to the extent of about 18-25 % of the total soluble sugars in the hydrolysate and 12-18 % of the total polysaccharides in the inlet biomass (untreated), equivalent to a yield loss of about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated). 26617670 2 89 from biomass 545:551 arg1 sugars 465:470 the total soluble sugars 447:470 the total soluble sugars in the hydrolysate 447:489 Recalcitrant oligosaccharides in AFEX-pretreated corn stover hydrolysate accumulate to the extent of about 18-25 % of the total soluble sugars in the hydrolysate and 12-18 % of the total polysaccharides in the inlet biomass (untreated), equivalent to a yield loss of about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated). 26617670 2 89 from biomass 545:551 arg1 % 442:442 about 18-25 % 430:442 about 18-25 % of the total soluble sugars in the hydrolysate 430:489 Recalcitrant oligosaccharides in AFEX-pretreated corn stover hydrolysate accumulate to the extent of about 18-25 % of the total soluble sugars in the hydrolysate and 12-18 % of the total polysaccharides in the inlet biomass (untreated), equivalent to a yield loss of about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated). 26617670 2 89 from biomass 545:551 arg1 % 501:501 12-18 % 495:501 12-18 % of the total polysaccharides in the inlet biomass (untreated), equivalent to a yield loss of about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated) 495:671 Recalcitrant oligosaccharides in AFEX-pretreated corn stover hydrolysate accumulate to the extent of about 18-25 % of the total soluble sugars in the hydrolysate and 12-18 % of the total polysaccharides in the inlet biomass (untreated), equivalent to a yield loss of about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated). 26617670 12 90 theme ratios 2241:2246 arg1 composition 2191:2201 The carbohydrate composition 2174:2201 The carbohydrate composition of the recalcitrant oligosaccharides, ratios of different DP oligomers and their distribution profiles 2174:2304 CONCLUSION The carbohydrate composition of the recalcitrant oligosaccharides, ratios of different DP oligomers and their distribution profiles were determined. 26617670 9 91 theme commercial 1787:1796 arg1 [Ctec2 1814:1819 [Ctec2 1814:1819 [Ctec2 1814:1819 Oligosaccharides with higher degree of polymerization (DP) were recalcitrant towards commercial enzyme mixtures [Ctec2, Htec2 and Multifect pectinase (MP)] compared to lower DP oligosaccharides. 26617670 9 91 theme commercial 1787:1796 arg1 mixtures 1805:1812 commercial enzyme mixtures [Ctec2, Htec2 and Multifect pectinase (MP)] 1787:1856 commercial enzyme mixtures [Ctec2, Htec2 and Multifect pectinase (MP)] 1787:1856 Oligosaccharides with higher degree of polymerization (DP) were recalcitrant towards commercial enzyme mixtures [Ctec2, Htec2 and Multifect pectinase (MP)] compared to lower DP oligosaccharides. 26617670 9 91 theme commercial 1787:1796 arg1 Htec2 1822:1826 Htec2 1822:1826 Htec2 1822:1826 Oligosaccharides with higher degree of polymerization (DP) were recalcitrant towards commercial enzyme mixtures [Ctec2, Htec2 and Multifect pectinase (MP)] compared to lower DP oligosaccharides. 26617670 9 91 theme commercial 1787:1796 arg1 pectinase 1842:1850 Multifect pectinase 1832:1850 Multifect pectinase (MP) 1832:1855 Oligosaccharides with higher degree of polymerization (DP) were recalcitrant towards commercial enzyme mixtures [Ctec2, Htec2 and Multifect pectinase (MP)] compared to lower DP oligosaccharides. 26617670 10 92 theme inhibition 1904:1913 arg1 studies 1915:1921 Enzyme inhibition studies 1897:1921 Enzyme inhibition studies using processed substrates (Avicel and xylan) 1897:1967 Enzyme inhibition studies using processed substrates (Avicel and xylan) showed that low DP oligosaccharides also inhibit commercial enzymes. 26617670 7 93 dep liquids 1428:1434 arg1 liquids 1428:1434 ionic liquids 1422:1434 ionic liquids: IL, and ammonia fibre expansion 1422:1467 RESULTS Oligosaccharide accumulation occurs during high solid loading enzymatic hydrolysis of corn stover (CS) irrespective of using different pretreated corn stover (dilute acid: DA, ionic liquids: IL, and ammonia fibre expansion: AFEX). 26617670 7 93 dep liquids 1428:1434 arg1 expansion 1459:1467 ammonia fibre expansion 1445:1467 ammonia fibre expansion 1445:1467 RESULTS Oligosaccharide accumulation occurs during high solid loading enzymatic hydrolysis of corn stover (CS) irrespective of using different pretreated corn stover (dilute acid: DA, ionic liquids: IL, and ammonia fibre expansion: AFEX). 26617670 7 93 dep liquids 1428:1434 arg1 IL 1437:1438 IL 1437:1438 IL 1437:1438 RESULTS Oligosaccharide accumulation occurs during high solid loading enzymatic hydrolysis of corn stover (CS) irrespective of using different pretreated corn stover (dilute acid: DA, ionic liquids: IL, and ammonia fibre expansion: AFEX). 26617670 7 94 theme ammonia 1445:1451 arg1 liquids 1428:1434 ionic liquids 1422:1434 ionic liquids: IL, and ammonia fibre expansion 1422:1467 RESULTS Oligosaccharide accumulation occurs during high solid loading enzymatic hydrolysis of corn stover (CS) irrespective of using different pretreated corn stover (dilute acid: DA, ionic liquids: IL, and ammonia fibre expansion: AFEX). 26617670 7 94 theme ammonia 1445:1451 arg1 expansion 1459:1467 ammonia fibre expansion 1445:1467 ammonia fibre expansion 1445:1467 RESULTS Oligosaccharide accumulation occurs during high solid loading enzymatic hydrolysis of corn stover (CS) irrespective of using different pretreated corn stover (dilute acid: DA, ionic liquids: IL, and ammonia fibre expansion: AFEX). 26617670 12 95 theme different 2251:2259 arg1 oligomers 2264:2272 different DP oligomers 2251:2272 different DP oligomers 2251:2272 CONCLUSION The carbohydrate composition of the recalcitrant oligosaccharides, ratios of different DP oligomers and their distribution profiles were determined. 26617670 3 96 theme biofuel 819:825 arg1 production 827:836 economical biofuel production 808:836 economical biofuel production from cellulosic biomass 808:860 These oligosaccharides represent a yield loss and also inhibit commercial hydrolytic enzymes, with both being serious bottlenecks for economical biofuel production from cellulosic biomass. 26617670 9 97 dep mixtures 1805:1812 arg1 [Ctec2 1814:1819 [Ctec2 1814:1819 [Ctec2 1814:1819 Oligosaccharides with higher degree of polymerization (DP) were recalcitrant towards commercial enzyme mixtures [Ctec2, Htec2 and Multifect pectinase (MP)] compared to lower DP oligosaccharides. 26617670 9 97 dep mixtures 1805:1812 arg1 mixtures 1805:1812 commercial enzyme mixtures [Ctec2, Htec2 and Multifect pectinase (MP)] 1787:1856 commercial enzyme mixtures [Ctec2, Htec2 and Multifect pectinase (MP)] 1787:1856 Oligosaccharides with higher degree of polymerization (DP) were recalcitrant towards commercial enzyme mixtures [Ctec2, Htec2 and Multifect pectinase (MP)] compared to lower DP oligosaccharides. 26617670 9 97 dep mixtures 1805:1812 arg1 MP 1853:1854 MP 1853:1854 MP 1853:1854 Oligosaccharides with higher degree of polymerization (DP) were recalcitrant towards commercial enzyme mixtures [Ctec2, Htec2 and Multifect pectinase (MP)] compared to lower DP oligosaccharides. 26617670 9 97 dep mixtures 1805:1812 arg1 Htec2 1822:1826 Htec2 1822:1826 Htec2 1822:1826 Oligosaccharides with higher degree of polymerization (DP) were recalcitrant towards commercial enzyme mixtures [Ctec2, Htec2 and Multifect pectinase (MP)] compared to lower DP oligosaccharides. 26617670 9 97 dep mixtures 1805:1812 arg1 pectinase 1842:1850 Multifect pectinase 1832:1850 Multifect pectinase (MP) 1832:1855 Oligosaccharides with higher degree of polymerization (DP) were recalcitrant towards commercial enzyme mixtures [Ctec2, Htec2 and Multifect pectinase (MP)] compared to lower DP oligosaccharides. 26617670 9 98 theme enzyme 1798:1803 arg1 [Ctec2 1814:1819 [Ctec2 1814:1819 [Ctec2 1814:1819 Oligosaccharides with higher degree of polymerization (DP) were recalcitrant towards commercial enzyme mixtures [Ctec2, Htec2 and Multifect pectinase (MP)] compared to lower DP oligosaccharides. 26617670 9 98 theme enzyme 1798:1803 arg1 mixtures 1805:1812 commercial enzyme mixtures [Ctec2, Htec2 and Multifect pectinase (MP)] 1787:1856 commercial enzyme mixtures [Ctec2, Htec2 and Multifect pectinase (MP)] 1787:1856 Oligosaccharides with higher degree of polymerization (DP) were recalcitrant towards commercial enzyme mixtures [Ctec2, Htec2 and Multifect pectinase (MP)] compared to lower DP oligosaccharides. 26617670 9 98 theme enzyme 1798:1803 arg1 Htec2 1822:1826 Htec2 1822:1826 Htec2 1822:1826 Oligosaccharides with higher degree of polymerization (DP) were recalcitrant towards commercial enzyme mixtures [Ctec2, Htec2 and Multifect pectinase (MP)] compared to lower DP oligosaccharides. 26617670 9 98 theme enzyme 1798:1803 arg1 pectinase 1842:1850 Multifect pectinase 1832:1850 Multifect pectinase (MP) 1832:1855 Oligosaccharides with higher degree of polymerization (DP) were recalcitrant towards commercial enzyme mixtures [Ctec2, Htec2 and Multifect pectinase (MP)] compared to lower DP oligosaccharides. 26617670 8 99 theme oligosaccharides 1536:1551 arg1 separation 1509:1518 large-scale separation 1497:1518 large-scale separation of recalcitrant oligosaccharides from 25 % solids-loading AFEX-corn stover hydrolysate using charcoal fractionation and size exclusion chromatography 1497:1668 The methodology for large-scale separation of recalcitrant oligosaccharides from 25 % solids-loading AFEX-corn stover hydrolysate using charcoal fractionation and size exclusion chromatography is reported for the first time. 26617670 14 100 with yields 2695:2700 arg1 enzyme 2712:2717 less enzyme 2707:2717 less enzyme 2707:2717 Such studies clarify the reasons for oligosaccharide accumulation and contribute to strategies by which oligosaccharides can be converted into fermentable sugars and provide higher biofuel yields with less enzyme. 26617670 1 101 theme recalcitrant 145:156 arg1 oligosaccharides 158:173 recalcitrant oligosaccharides 145:173 recalcitrant oligosaccharides 145:173 BACKGROUND Accumulation of recalcitrant oligosaccharides during high-solids loading enzymatic hydrolysis of cellulosic biomass reduces biofuel yields and increases processing costs for a cellulosic biorefinery. 26617670 6 102 theme chemical 1221:1228 arg1 nature 1230:1235 their chemical nature 1215:1235 their chemical nature 1215:1235 Composition analysis, recalcitrance study and enzyme inhibition study were performed to understand their chemical nature. 26617670 8 103 theme 25  1558:1560 arg1 % 1561:1561 % 1561:1561 % 1561:1561 The methodology for large-scale separation of recalcitrant oligosaccharides from 25 % solids-loading AFEX-corn stover hydrolysate using charcoal fractionation and size exclusion chromatography is reported for the first time. 26617670 12 104 theme oligosaccharides 2223:2238 arg1 composition 2191:2201 The carbohydrate composition 2174:2201 The carbohydrate composition of the recalcitrant oligosaccharides, ratios of different DP oligomers and their distribution profiles 2174:2304 CONCLUSION The carbohydrate composition of the recalcitrant oligosaccharides, ratios of different DP oligomers and their distribution profiles were determined. 26617670 4 105 theme oligomers 915:923 arg1 nature 899:904 the nature 895:904 the nature of these oligomers 895:923 Very little is understood about the nature of these oligomers and why they are recalcitrant to commercial enzymes. 26617670 2 106 from % 501:501 arg1 hydrolysate 479:489 the hydrolysate 475:489 the hydrolysate 475:489 Recalcitrant oligosaccharides in AFEX-pretreated corn stover hydrolysate accumulate to the extent of about 18-25 % of the total soluble sugars in the hydrolysate and 12-18 % of the total polysaccharides in the inlet biomass (untreated), equivalent to a yield loss of about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated). 26617670 2 106 from % 501:501 arg1 biomass 545:551 the inlet biomass 535:551 the inlet biomass (untreated) 535:563 Recalcitrant oligosaccharides in AFEX-pretreated corn stover hydrolysate accumulate to the extent of about 18-25 % of the total soluble sugars in the hydrolysate and 12-18 % of the total polysaccharides in the inlet biomass (untreated), equivalent to a yield loss of about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated). 26617670 7 107 theme ionic 1422:1426 arg1 liquids 1428:1434 ionic liquids 1422:1434 ionic liquids: IL, and ammonia fibre expansion 1422:1467 RESULTS Oligosaccharide accumulation occurs during high solid loading enzymatic hydrolysis of corn stover (CS) irrespective of using different pretreated corn stover (dilute acid: DA, ionic liquids: IL, and ammonia fibre expansion: AFEX). 26617670 7 107 theme ionic 1422:1426 arg1 expansion 1459:1467 ammonia fibre expansion 1445:1467 ammonia fibre expansion 1445:1467 RESULTS Oligosaccharide accumulation occurs during high solid loading enzymatic hydrolysis of corn stover (CS) irrespective of using different pretreated corn stover (dilute acid: DA, ionic liquids: IL, and ammonia fibre expansion: AFEX). 26617670 7 107 theme ionic 1422:1426 arg1 IL 1437:1438 IL 1437:1438 IL 1437:1438 RESULTS Oligosaccharide accumulation occurs during high solid loading enzymatic hydrolysis of corn stover (CS) irrespective of using different pretreated corn stover (dilute acid: DA, ionic liquids: IL, and ammonia fibre expansion: AFEX). 26617670 7 108 theme loading 1300:1306 arg1 hydrolysis 1318:1327 high solid loading enzymatic hydrolysis 1289:1327 high solid loading enzymatic hydrolysis of corn stover (CS) irrespective of using different pretreated corn stover (dilute acid: DA, ionic liquids: IL, and ammonia fibre expansion: AFEX) 1289:1474 RESULTS Oligosaccharide accumulation occurs during high solid loading enzymatic hydrolysis of corn stover (CS) irrespective of using different pretreated corn stover (dilute acid: DA, ionic liquids: IL, and ammonia fibre expansion: AFEX). 26617670 0 109 theme solids-loading 81:94 arg1 hydrolysis 106:115 high solids-loading enzymatic hydrolysis 76:115 high solids-loading enzymatic hydrolysis 76:115 Sugar loss and enzyme inhibition due to oligosaccharide accumulation during high solids-loading enzymatic hydrolysis. 26617670 1 110 theme loading 194:200 arg1 hydrolysis 212:221 high-solids loading enzymatic hydrolysis 182:221 high-solids loading enzymatic hydrolysis of cellulosic biomass 182:243 BACKGROUND Accumulation of recalcitrant oligosaccharides during high-solids loading enzymatic hydrolysis of cellulosic biomass reduces biofuel yields and increases processing costs for a cellulosic biorefinery. 26617670 2 111 theme inlet 539:543 arg1 biomass 545:551 the inlet biomass 535:551 the inlet biomass (untreated) 535:563 Recalcitrant oligosaccharides in AFEX-pretreated corn stover hydrolysate accumulate to the extent of about 18-25 % of the total soluble sugars in the hydrolysate and 12-18 % of the total polysaccharides in the inlet biomass (untreated), equivalent to a yield loss of about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated). 26617670 8 112 theme stover 1588:1593 arg1 hydrolysate 1595:1605 25 % solids-loading AFEX-corn stover hydrolysate 1558:1605 25 % solids-loading AFEX-corn stover hydrolysate using charcoal fractionation and size exclusion chromatography 1558:1668 The methodology for large-scale separation of recalcitrant oligosaccharides from 25 % solids-loading AFEX-corn stover hydrolysate using charcoal fractionation and size exclusion chromatography is reported for the first time. 26617670 8 113 theme large-scale 1497:1507 arg1 separation 1509:1518 large-scale separation 1497:1518 large-scale separation of recalcitrant oligosaccharides from 25 % solids-loading AFEX-corn stover hydrolysate using charcoal fractionation and size exclusion chromatography 1497:1668 The methodology for large-scale separation of recalcitrant oligosaccharides from 25 % solids-loading AFEX-corn stover hydrolysate using charcoal fractionation and size exclusion chromatography is reported for the first time. 26617670 7 114 theme solid 1294:1298 arg1 hydrolysis 1318:1327 high solid loading enzymatic hydrolysis 1289:1327 high solid loading enzymatic hydrolysis of corn stover (CS) irrespective of using different pretreated corn stover (dilute acid: DA, ionic liquids: IL, and ammonia fibre expansion: AFEX) 1289:1474 RESULTS Oligosaccharide accumulation occurs during high solid loading enzymatic hydrolysis of corn stover (CS) irrespective of using different pretreated corn stover (dilute acid: DA, ionic liquids: IL, and ammonia fibre expansion: AFEX). 26617670 5 115 theme robust 999:1004 arg1 method 1006:1011 a robust method 997:1011 a robust method for separating recalcitrant oligosaccharides from high solid loading hydrolysate in gramme quantities 997:1113 This work presents a robust method for separating recalcitrant oligosaccharides from high solid loading hydrolysate in gramme quantities. 26617670 2 116 theme equivalent 566:575 arg1 biomass 545:551 the inlet biomass 535:551 the inlet biomass (untreated) 535:563 Recalcitrant oligosaccharides in AFEX-pretreated corn stover hydrolysate accumulate to the extent of about 18-25 % of the total soluble sugars in the hydrolysate and 12-18 % of the total polysaccharides in the inlet biomass (untreated), equivalent to a yield loss of about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated). 26617670 2 117 from polysaccharides 516:530 arg1 biomass 545:551 the inlet biomass 535:551 the inlet biomass (untreated) 535:563 Recalcitrant oligosaccharides in AFEX-pretreated corn stover hydrolysate accumulate to the extent of about 18-25 % of the total soluble sugars in the hydrolysate and 12-18 % of the total polysaccharides in the inlet biomass (untreated), equivalent to a yield loss of about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated). 26617670 13 118 theme plant 2489:2493 arg1 wall 2500:2503 the plant cell wall 2485:2503 the plant cell wall 2485:2503 Recalcitrance and enzyme inhibition studies help determine whether the commercial enzyme mixtures lack the enzyme activities required to completely de-polymerize the plant cell wall. 26617670 9 119 theme DP 1876:1877 arg1 oligosaccharides 1879:1894 lower DP oligosaccharides 1870:1894 lower DP oligosaccharides 1870:1894 Oligosaccharides with higher degree of polymerization (DP) were recalcitrant towards commercial enzyme mixtures [Ctec2, Htec2 and Multifect pectinase (MP)] compared to lower DP oligosaccharides. 26617670 2 120 theme soluble 457:463 arg1 sugars 465:470 the total soluble sugars 447:470 the total soluble sugars in the hydrolysate 447:489 Recalcitrant oligosaccharides in AFEX-pretreated corn stover hydrolysate accumulate to the extent of about 18-25 % of the total soluble sugars in the hydrolysate and 12-18 % of the total polysaccharides in the inlet biomass (untreated), equivalent to a yield loss of about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated). 26617670 7 121 theme dilute 1405:1410 arg1 stover 1397:1402 different pretreated corn stover 1371:1402 different pretreated corn stover (dilute acid: DA, ionic liquids: IL, and ammonia fibre expansion: AFEX) 1371:1474 RESULTS Oligosaccharide accumulation occurs during high solid loading enzymatic hydrolysis of corn stover (CS) irrespective of using different pretreated corn stover (dilute acid: DA, ionic liquids: IL, and ammonia fibre expansion: AFEX). 26617670 7 121 theme dilute 1405:1410 arg1 acid 1412:1415 dilute acid 1405:1415 dilute acid 1405:1415 RESULTS Oligosaccharide accumulation occurs during high solid loading enzymatic hydrolysis of corn stover (CS) irrespective of using different pretreated corn stover (dilute acid: DA, ionic liquids: IL, and ammonia fibre expansion: AFEX). 26617670 8 122 theme size 1640:1643 arg1 chromatography 1655:1668 charcoal fractionation and size exclusion chromatography 1613:1668 chromatography 1655:1668 The methodology for large-scale separation of recalcitrant oligosaccharides from 25 % solids-loading AFEX-corn stover hydrolysate using charcoal fractionation and size exclusion chromatography is reported for the first time. 26617670 11 123 theme commercial 2143:2152 arg1 enzymes 2154:2160 commercial enzymes 2143:2160 commercial enzymes 2143:2160 Addition of monomeric sugars to oligosaccharides increases the inhibitory effects of oligosaccharides on commercial enzymes. 26617670 0 124 theme enzyme 15:20 arg1 inhibition 22:31 enzyme inhibition 15:31 enzyme inhibition 15:31 Sugar loss and enzyme inhibition due to oligosaccharide accumulation during high solids-loading enzymatic hydrolysis. 26617670 13 125 theme commercial 2394:2403 arg1 mixtures 2412:2419 the commercial enzyme mixtures 2390:2419 the commercial enzyme mixtures 2390:2419 Recalcitrance and enzyme inhibition studies help determine whether the commercial enzyme mixtures lack the enzyme activities required to completely de-polymerize the plant cell wall. 26617670 11 126 theme sugars 2060:2065 arg1 Addition 2038:2045 Addition 2038:2045 Addition of monomeric sugars to oligosaccharides 2038:2085 Addition of monomeric sugars to oligosaccharides increases the inhibitory effects of oligosaccharides on commercial enzymes. 26617670 6 127 theme Composition 1116:1126 arg1 analysis 1128:1135 Composition analysis 1116:1135 Composition analysis 1116:1135 Composition analysis, recalcitrance study and enzyme inhibition study were performed to understand their chemical nature. 26617670 13 128 theme cell 2495:2498 arg1 wall 2500:2503 the plant cell wall 2485:2503 the plant cell wall 2485:2503 Recalcitrance and enzyme inhibition studies help determine whether the commercial enzyme mixtures lack the enzyme activities required to completely de-polymerize the plant cell wall. 26617670 5 129 theme solid 1068:1072 arg1 hydrolysate 1082:1092 high solid loading hydrolysate 1063:1092 high solid loading hydrolysate 1063:1092 This work presents a robust method for separating recalcitrant oligosaccharides from high solid loading hydrolysate in gramme quantities. 26617670 7 130 theme pretreated 1381:1390 arg1 stover 1397:1402 different pretreated corn stover 1371:1402 different pretreated corn stover (dilute acid: DA, ionic liquids: IL, and ammonia fibre expansion: AFEX) 1371:1474 RESULTS Oligosaccharide accumulation occurs during high solid loading enzymatic hydrolysis of corn stover (CS) irrespective of using different pretreated corn stover (dilute acid: DA, ionic liquids: IL, and ammonia fibre expansion: AFEX). 26617670 7 130 theme pretreated 1381:1390 arg1 acid 1412:1415 dilute acid 1405:1415 dilute acid 1405:1415 RESULTS Oligosaccharide accumulation occurs during high solid loading enzymatic hydrolysis of corn stover (CS) irrespective of using different pretreated corn stover (dilute acid: DA, ionic liquids: IL, and ammonia fibre expansion: AFEX). 26617670 0 131 theme oligosaccharide 40:54 arg1 accumulation 56:67 oligosaccharide accumulation 40:67 oligosaccharide accumulation 40:67 Sugar loss and enzyme inhibition due to oligosaccharide accumulation during high solids-loading enzymatic hydrolysis. 26617670 2 132 dep biomass 545:551 arg1 untreated 554:562 untreated 554:562 untreated 554:562 Recalcitrant oligosaccharides in AFEX-pretreated corn stover hydrolysate accumulate to the extent of about 18-25 % of the total soluble sugars in the hydrolysate and 12-18 % of the total polysaccharides in the inlet biomass (untreated), equivalent to a yield loss of about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated). 26617670 2 133 theme total 510:514 arg1 polysaccharides 516:530 the total polysaccharides 506:530 the total polysaccharides in the inlet biomass (untreated), equivalent to a yield loss of about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated) 506:671 Recalcitrant oligosaccharides in AFEX-pretreated corn stover hydrolysate accumulate to the extent of about 18-25 % of the total soluble sugars in the hydrolysate and 12-18 % of the total polysaccharides in the inlet biomass (untreated), equivalent to a yield loss of about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated). 26617670 10 134 theme low 1981:1983 arg1 oligosaccharides 1988:2003 low DP oligosaccharides 1981:2003 low DP oligosaccharides 1981:2003 Enzyme inhibition studies using processed substrates (Avicel and xylan) showed that low DP oligosaccharides also inhibit commercial enzymes. 26617670 5 135 theme recalcitrant 1028:1039 arg1 oligosaccharides 1041:1056 recalcitrant oligosaccharides 1028:1056 recalcitrant oligosaccharides from high solid loading hydrolysate 1028:1092 This work presents a robust method for separating recalcitrant oligosaccharides from high solid loading hydrolysate in gramme quantities. 26617670 10 136 theme Enzyme 1897:1902 arg1 studies 1915:1921 Enzyme inhibition studies 1897:1921 Enzyme inhibition studies using processed substrates (Avicel and xylan) 1897:1967 Enzyme inhibition studies using processed substrates (Avicel and xylan) showed that low DP oligosaccharides also inhibit commercial enzymes. 26617670 7 137 theme irrespective 1349:1360 arg1 CS 1345:1346 CS 1345:1346 CS 1345:1346 RESULTS Oligosaccharide accumulation occurs during high solid loading enzymatic hydrolysis of corn stover (CS) irrespective of using different pretreated corn stover (dilute acid: DA, ionic liquids: IL, and ammonia fibre expansion: AFEX). 26617670 7 137 theme irrespective 1349:1360 arg1 stover 1337:1342 corn stover 1332:1342 corn stover (CS) irrespective of using different pretreated corn stover (dilute acid: DA, ionic liquids: IL, and ammonia fibre expansion: AFEX) 1332:1474 RESULTS Oligosaccharide accumulation occurs during high solid loading enzymatic hydrolysis of corn stover (CS) irrespective of using different pretreated corn stover (dilute acid: DA, ionic liquids: IL, and ammonia fibre expansion: AFEX). 26617670 3 138 from biomass 854:860 arg1 production 827:836 economical biofuel production 808:836 economical biofuel production from cellulosic biomass 808:860 These oligosaccharides represent a yield loss and also inhibit commercial hydrolytic enzymes, with both being serious bottlenecks for economical biofuel production from cellulosic biomass. 26617670 12 139 theme profiles 2297:2304 arg1 composition 2191:2201 The carbohydrate composition 2174:2201 The carbohydrate composition of the recalcitrant oligosaccharides, ratios of different DP oligomers and their distribution profiles 2174:2304 CONCLUSION The carbohydrate composition of the recalcitrant oligosaccharides, ratios of different DP oligomers and their distribution profiles were determined. 26617670 11 140 theme inhibitory 2101:2110 arg1 effects 2112:2118 the inhibitory effects 2097:2118 the inhibitory effects of oligosaccharides on commercial enzymes 2097:2160 Addition of monomeric sugars to oligosaccharides increases the inhibitory effects of oligosaccharides on commercial enzymes. 26617670 1 141 theme processing 282:291 arg1 costs 293:297 processing costs 282:297 processing costs for a cellulosic biorefinery 282:326 BACKGROUND Accumulation of recalcitrant oligosaccharides during high-solids loading enzymatic hydrolysis of cellulosic biomass reduces biofuel yields and increases processing costs for a cellulosic biorefinery. 26617670 2 142 theme % 442:442 arg1 extent 420:425 the extent 416:425 the extent of about 18-25 % of the total soluble sugars in the hydrolysate and 12-18 % of the total polysaccharides in the inlet biomass (untreated), equivalent to a yield loss of about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated) 416:671 Recalcitrant oligosaccharides in AFEX-pretreated corn stover hydrolysate accumulate to the extent of about 18-25 % of the total soluble sugars in the hydrolysate and 12-18 % of the total polysaccharides in the inlet biomass (untreated), equivalent to a yield loss of about 7-9 kg of monomeric sugars per 100 kg of inlet dry biomass (untreated). 26617670 13 143 theme inhibition 2348:2357 arg1 studies 2359:2365 enzyme inhibition studies 2341:2365 enzyme inhibition studies 2341:2365 Recalcitrance and enzyme inhibition studies help determine whether the commercial enzyme mixtures lack the enzyme activities required to completely de-polymerize the plant cell wall. 24247556 0 0 theme charge 91:96 arg1 processes 107:115 the charge transfer processes 87:115 the charge transfer processes of polyaniline 87:130 Electronic communication across N-linked unconjugated polymers: important insight into the charge transfer processes of polyaniline. 24247556 1 1 theme charge 168:173 arg1 bands 184:188 The [C6H4C≡CPtL2C≡CC6H4] → quinone charge transfer bands 133:188 The [C6H4C≡CPtL2C≡CC6H4] → quinone charge transfer bands in unconjugated ([Pt]-NMe-Q)n's 133:220 The [C6H4C≡CPtL2C≡CC6H4] → quinone charge transfer bands in unconjugated ([Pt]-NMe-Q)n's are similar to the conjugated systems showing that the NMe secures communication. 24247556 1 1 theme charge 168:173 arg1 similar 226:232 similar 226:232 similar 226:232 The [C6H4C≡CPtL2C≡CC6H4] → quinone charge transfer bands in unconjugated ([Pt]-NMe-Q)n's are similar to the conjugated systems showing that the NMe secures communication. 24247556 1 2 theme → 158:158 arg1 bands 184:188 The [C6H4C≡CPtL2C≡CC6H4] → quinone charge transfer bands 133:188 The [C6H4C≡CPtL2C≡CC6H4] → quinone charge transfer bands in unconjugated ([Pt]-NMe-Q)n's 133:220 The [C6H4C≡CPtL2C≡CC6H4] → quinone charge transfer bands in unconjugated ([Pt]-NMe-Q)n's are similar to the conjugated systems showing that the NMe secures communication. 24247556 1 2 theme → 158:158 arg1 similar 226:232 similar 226:232 similar 226:232 The [C6H4C≡CPtL2C≡CC6H4] → quinone charge transfer bands in unconjugated ([Pt]-NMe-Q)n's are similar to the conjugated systems showing that the NMe secures communication. 24247556 1 3 theme -NMe-Q 211:216 arg1 s 220:220 unconjugated ([Pt]-NMe-Q)n's 193:220 unconjugated ([Pt]-NMe-Q)n's 193:220 The [C6H4C≡CPtL2C≡CC6H4] → quinone charge transfer bands in unconjugated ([Pt]-NMe-Q)n's are similar to the conjugated systems showing that the NMe secures communication. 24247556 1 3 theme -NMe-Q 211:216 arg1 [Pt 207:209 [Pt 207:209 [Pt 207:209 The [C6H4C≡CPtL2C≡CC6H4] → quinone charge transfer bands in unconjugated ([Pt]-NMe-Q)n's are similar to the conjugated systems showing that the NMe secures communication. 24247556 0 4 link N-linked 32:39 arg1 polymers 54:61 N-linked unconjugated polymers 32:61 N-linked unconjugated polymers 32:61 Electronic communication across N-linked unconjugated polymers: important insight into the charge transfer processes of polyaniline. 24247556 1 5 theme transfer 175:182 arg1 bands 184:188 The [C6H4C≡CPtL2C≡CC6H4] → quinone charge transfer bands 133:188 The [C6H4C≡CPtL2C≡CC6H4] → quinone charge transfer bands in unconjugated ([Pt]-NMe-Q)n's 133:220 The [C6H4C≡CPtL2C≡CC6H4] → quinone charge transfer bands in unconjugated ([Pt]-NMe-Q)n's are similar to the conjugated systems showing that the NMe secures communication. 24247556 1 5 theme transfer 175:182 arg1 similar 226:232 similar 226:232 similar 226:232 The [C6H4C≡CPtL2C≡CC6H4] → quinone charge transfer bands in unconjugated ([Pt]-NMe-Q)n's are similar to the conjugated systems showing that the NMe secures communication. 24247556 1 6 theme n' 218:219 arg1 s 220:220 unconjugated ([Pt]-NMe-Q)n's 193:220 unconjugated ([Pt]-NMe-Q)n's 193:220 The [C6H4C≡CPtL2C≡CC6H4] → quinone charge transfer bands in unconjugated ([Pt]-NMe-Q)n's are similar to the conjugated systems showing that the NMe secures communication. 24247556 1 6 theme n' 218:219 arg1 [Pt 207:209 [Pt 207:209 [Pt 207:209 The [C6H4C≡CPtL2C≡CC6H4] → quinone charge transfer bands in unconjugated ([Pt]-NMe-Q)n's are similar to the conjugated systems showing that the NMe secures communication. 24247556 0 7 theme unconjugated 41:52 arg1 polymers 54:61 N-linked unconjugated polymers 32:61 N-linked unconjugated polymers 32:61 Electronic communication across N-linked unconjugated polymers: important insight into the charge transfer processes of polyaniline. 24247556 1 8 theme unconjugated 193:204 arg1 s 220:220 unconjugated ([Pt]-NMe-Q)n's 193:220 unconjugated ([Pt]-NMe-Q)n's 193:220 The [C6H4C≡CPtL2C≡CC6H4] → quinone charge transfer bands in unconjugated ([Pt]-NMe-Q)n's are similar to the conjugated systems showing that the NMe secures communication. 24247556 1 8 theme unconjugated 193:204 arg1 [Pt 207:209 [Pt 207:209 [Pt 207:209 The [C6H4C≡CPtL2C≡CC6H4] → quinone charge transfer bands in unconjugated ([Pt]-NMe-Q)n's are similar to the conjugated systems showing that the NMe secures communication. 24247556 0 9 theme Electronic 0:9 arg1 communication 11:23 Electronic communication 0:23 Electronic communication across N-linked unconjugated polymers: important insight into the charge transfer processes of polyaniline. 0:131 Electronic communication across N-linked unconjugated polymers: important insight into the charge transfer processes of polyaniline. 24247556 0 10 theme important 64:72 arg1 insight 74:80 important insight 64:80 Electronic communication across N-linked unconjugated polymers: important insight into the charge transfer processes of polyaniline. 0:131 Electronic communication across N-linked unconjugated polymers: important insight into the charge transfer processes of polyaniline. 24247556 0 11 theme transfer 98:105 arg1 processes 107:115 the charge transfer processes 87:115 the charge transfer processes of polyaniline 87:130 Electronic communication across N-linked unconjugated polymers: important insight into the charge transfer processes of polyaniline. 24247556 1 12 theme conjugated 241:250 arg1 systems 252:258 the conjugated systems 237:258 the conjugated systems showing that the NMe secures communication 237:301 The [C6H4C≡CPtL2C≡CC6H4] → quinone charge transfer bands in unconjugated ([Pt]-NMe-Q)n's are similar to the conjugated systems showing that the NMe secures communication. 24247556 0 13 theme N-linked 32:39 arg1 polymers 54:61 N-linked unconjugated polymers 32:61 N-linked unconjugated polymers 32:61 Electronic communication across N-linked unconjugated polymers: important insight into the charge transfer processes of polyaniline. 24247556 0 14 dep communication 11:23 arg1 insight 74:80 important insight 64:80 Electronic communication across N-linked unconjugated polymers: important insight into the charge transfer processes of polyaniline. 0:131 Electronic communication across N-linked unconjugated polymers: important insight into the charge transfer processes of polyaniline. 24247556 1 15 from bands 184:188 arg1 s 220:220 unconjugated ([Pt]-NMe-Q)n's 193:220 unconjugated ([Pt]-NMe-Q)n's 193:220 The [C6H4C≡CPtL2C≡CC6H4] → quinone charge transfer bands in unconjugated ([Pt]-NMe-Q)n's are similar to the conjugated systems showing that the NMe secures communication. 24247556 1 15 from bands 184:188 arg1 [Pt 207:209 [Pt 207:209 [Pt 207:209 The [C6H4C≡CPtL2C≡CC6H4] → quinone charge transfer bands in unconjugated ([Pt]-NMe-Q)n's are similar to the conjugated systems showing that the NMe secures communication. 24247556 0 16 theme polyaniline 120:130 arg1 processes 107:115 the charge transfer processes 87:115 the charge transfer processes of polyaniline 87:130 Electronic communication across N-linked unconjugated polymers: important insight into the charge transfer processes of polyaniline. 24247556 1 17 theme quinone 160:166 arg1 bands 184:188 The [C6H4C≡CPtL2C≡CC6H4] → quinone charge transfer bands 133:188 The [C6H4C≡CPtL2C≡CC6H4] → quinone charge transfer bands in unconjugated ([Pt]-NMe-Q)n's 133:220 The [C6H4C≡CPtL2C≡CC6H4] → quinone charge transfer bands in unconjugated ([Pt]-NMe-Q)n's are similar to the conjugated systems showing that the NMe secures communication. 24247556 1 17 theme quinone 160:166 arg1 similar 226:232 similar 226:232 similar 226:232 The [C6H4C≡CPtL2C≡CC6H4] → quinone charge transfer bands in unconjugated ([Pt]-NMe-Q)n's are similar to the conjugated systems showing that the NMe secures communication. 27440076 0 0 theme recombinant 73:83 arg1 IIa 99:101 recombinant endoglucanase IIa 73:101 recombinant endoglucanase IIa (Cel5A) 73:109 Effect of N-linked glycosylation on the activity and other properties of recombinant endoglucanase IIa (Cel5A) from Penicillium verruculosum. 27440076 0 0 theme recombinant 73:83 arg1 Cel5A 104:108 Cel5A 104:108 Cel5A 104:108 Effect of N-linked glycosylation on the activity and other properties of recombinant endoglucanase IIa (Cel5A) from Penicillium verruculosum. 27440076 9 1 theme prolonged 1365:1373 arg1 hydrolysis 1375:1384 prolonged hydrolysis 1365:1384 prolonged hydrolysis of β-glucan and milled aspen wood by rPvCel5A forms 1365:1436 Similar effects of the mutations were observed in prolonged hydrolysis of β-glucan and milled aspen wood by rPvCel5A forms in the presence of purified β-glucosidase. 27440076 1 2 from verruculosum 177:188 arg1 IIa 156:158 Endoglucanase IIa 142:158 Endoglucanase IIa from Penicillium verruculosum (PvCel5A) 142:198 Endoglucanase IIa from Penicillium verruculosum (PvCel5A) has three potential N-glycosylation sites: Asn19, Asn42 and Asn194. 27440076 9 3 theme β-glucan 1389:1396 arg1 wood 1415:1418 β-glucan and milled aspen wood 1389:1418 β-glucan and milled aspen wood 1389:1418 Similar effects of the mutations were observed in prolonged hydrolysis of β-glucan and milled aspen wood by rPvCel5A forms in the presence of purified β-glucosidase. 27440076 4 4 theme mass 542:545 arg1 fingerprinting 568:581 The MALDI-TOF mass spectrometry peptide fingerprinting 528:581 The MALDI-TOF mass spectrometry peptide fingerprinting 528:581 The MALDI-TOF mass spectrometry peptide fingerprinting showed that N-glycans linked to Asn42 and Asn194 represent variable oligosaccharides, according to the formula (Man)1-9(GlcNAc)2. 27440076 6 5 contain had 770:772 arg1 Mutations 760:768 Mutations 760:768 Mutations 760:768 Mutations had no notable effect on the enzyme thermostability; however, the N-linked glycans stabilized the enzyme against proteolytic attack. 27440076 6 5 contain had 770:772 arg2 effect 785:790 no notable effect 774:790 no notable effect 774:790 Mutations had no notable effect on the enzyme thermostability; however, the N-linked glycans stabilized the enzyme against proteolytic attack. 27440076 1 6 contain has 200:202 arg2 Asn194 260:265 Asn194 260:265 Asn194 260:265 Endoglucanase IIa from Penicillium verruculosum (PvCel5A) has three potential N-glycosylation sites: Asn19, Asn42 and Asn194. 27440076 1 6 contain has 200:202 arg2 Asn19 243:247 Asn19 243:247 Asn19 243:247 Endoglucanase IIa from Penicillium verruculosum (PvCel5A) has three potential N-glycosylation sites: Asn19, Asn42 and Asn194. 27440076 1 6 contain has 200:202 arg2 Asn42 250:254 Asn42 250:254 Asn42 250:254 Endoglucanase IIa from Penicillium verruculosum (PvCel5A) has three potential N-glycosylation sites: Asn19, Asn42 and Asn194. 27440076 1 6 contain has 200:202 arg1 IIa 156:158 Endoglucanase IIa 142:158 Endoglucanase IIa from Penicillium verruculosum (PvCel5A) 142:198 Endoglucanase IIa from Penicillium verruculosum (PvCel5A) has three potential N-glycosylation sites: Asn19, Asn42 and Asn194. 27440076 1 6 contain has 200:202 arg2 sites 236:240 three potential N-glycosylation sites 204:240 three potential N-glycosylation sites: Asn19, Asn42 and Asn194 204:265 Endoglucanase IIa from Penicillium verruculosum (PvCel5A) has three potential N-glycosylation sites: Asn19, Asn42 and Asn194. 27440076 8 7 theme specific 1111:1118 arg1 activity 1120:1127 the specific activity 1107:1127 the specific activity against carboxymethylcellulose and barley β-glucan (by 26% and 12% relative to the rPvCel5A-wt) 1107:1223 The N19A mutation led to a notable decrease in the specific activity against carboxymethylcellulose and barley β-glucan (by 26% and 12% relative to the rPvCel5A-wt), while the N42A and N194A mutants displayed 12-13% and 32-35% increase in the activities. 27440076 2 8 theme type 324:327 arg1 PvCel5A 334:340 the wild type (wt) PvCel5A 315:340 the wild type (wt) PvCel5A 315:340 In order to study the role of N-glycosylation, the wild type (wt) PvCel5A and its mutant forms, carrying Asn to Ala substitutions, were cloned into Penicillium canescens. 27440076 4 9 theme MALDI-TOF 532:540 arg1 fingerprinting 568:581 The MALDI-TOF mass spectrometry peptide fingerprinting 528:581 The MALDI-TOF mass spectrometry peptide fingerprinting 528:581 The MALDI-TOF mass spectrometry peptide fingerprinting showed that N-glycans linked to Asn42 and Asn194 represent variable oligosaccharides, according to the formula (Man)1-9(GlcNAc)2. 27440076 0 10 theme IIa 99:101 arg1 activity 40:47 activity 40:47 activity 40:47 Effect of N-linked glycosylation on the activity and other properties of recombinant endoglucanase IIa (Cel5A) from Penicillium verruculosum. 27440076 0 10 theme IIa 99:101 arg1 properties 59:68 other properties 53:68 other properties 53:68 Effect of N-linked glycosylation on the activity and other properties of recombinant endoglucanase IIa (Cel5A) from Penicillium verruculosum. 27440076 0 11 from Effect 0:5 arg1 activity 40:47 activity 40:47 activity 40:47 Effect of N-linked glycosylation on the activity and other properties of recombinant endoglucanase IIa (Cel5A) from Penicillium verruculosum. 27440076 0 11 from Effect 0:5 arg1 properties 59:68 other properties 53:68 other properties 53:68 Effect of N-linked glycosylation on the activity and other properties of recombinant endoglucanase IIa (Cel5A) from Penicillium verruculosum. 27440076 1 12 gly N-glycosylation 220:234 arg2 Asn194 260:265 Asn194 260:265 Asn194 260:265 Endoglucanase IIa from Penicillium verruculosum (PvCel5A) has three potential N-glycosylation sites: Asn19, Asn42 and Asn194. 27440076 1 12 gly N-glycosylation 220:234 arg2 Asn42 250:254 Asn42 250:254 Asn42 250:254 Endoglucanase IIa from Penicillium verruculosum (PvCel5A) has three potential N-glycosylation sites: Asn19, Asn42 and Asn194. 27440076 1 12 gly N-glycosylation 220:234 arg2 three 204:208 three 204:208 three 204:208 Endoglucanase IIa from Penicillium verruculosum (PvCel5A) has three potential N-glycosylation sites: Asn19, Asn42 and Asn194. 27440076 1 12 gly N-glycosylation 220:234 arg2 Asn19 243:247 Asn19 243:247 Asn19 243:247 Endoglucanase IIa from Penicillium verruculosum (PvCel5A) has three potential N-glycosylation sites: Asn19, Asn42 and Asn194. 27440076 1 12 gly N-glycosylation 220:234 arg2 sites 236:240 three potential N-glycosylation sites 204:240 three potential N-glycosylation sites: Asn19, Asn42 and Asn194 204:265 Endoglucanase IIa from Penicillium verruculosum (PvCel5A) has three potential N-glycosylation sites: Asn19, Asn42 and Asn194. 27440076 9 13 theme milled 1402:1407 arg1 wood 1415:1418 β-glucan and milled aspen wood 1389:1418 β-glucan and milled aspen wood 1389:1418 Similar effects of the mutations were observed in prolonged hydrolysis of β-glucan and milled aspen wood by rPvCel5A forms in the presence of purified β-glucosidase. 27440076 4 14 theme peptide 560:566 arg1 fingerprinting 568:581 The MALDI-TOF mass spectrometry peptide fingerprinting 528:581 The MALDI-TOF mass spectrometry peptide fingerprinting 528:581 The MALDI-TOF mass spectrometry peptide fingerprinting showed that N-glycans linked to Asn42 and Asn194 represent variable oligosaccharides, according to the formula (Man)1-9(GlcNAc)2. 27440076 0 15 theme endoglucanase 85:97 arg1 IIa 99:101 recombinant endoglucanase IIa 73:101 recombinant endoglucanase IIa (Cel5A) 73:109 Effect of N-linked glycosylation on the activity and other properties of recombinant endoglucanase IIa (Cel5A) from Penicillium verruculosum. 27440076 0 15 theme endoglucanase 85:97 arg1 Cel5A 104:108 Cel5A 104:108 Cel5A 104:108 Effect of N-linked glycosylation on the activity and other properties of recombinant endoglucanase IIa (Cel5A) from Penicillium verruculosum. 27440076 6 16 theme N-linked 836:843 arg1 glycans 845:851 the N-linked glycans 832:851 the N-linked glycans 832:851 Mutations had no notable effect on the enzyme thermostability; however, the N-linked glycans stabilized the enzyme against proteolytic attack. 27440076 9 17 theme aspen 1409:1413 arg1 wood 1415:1418 β-glucan and milled aspen wood 1389:1418 β-glucan and milled aspen wood 1389:1418 Similar effects of the mutations were observed in prolonged hydrolysis of β-glucan and milled aspen wood by rPvCel5A forms in the presence of purified β-glucosidase. 27440076 4 18 theme Man 695:697 arg1 GlcNAc 703:708 the formula (Man)1-9(GlcNAc)2 682:710 the formula (Man)1-9(GlcNAc)2 682:710 The MALDI-TOF mass spectrometry peptide fingerprinting showed that N-glycans linked to Asn42 and Asn194 represent variable oligosaccharides, according to the formula (Man)1-9(GlcNAc)2. 27440076 9 19 theme wood 1415:1418 arg1 hydrolysis 1375:1384 prolonged hydrolysis 1365:1384 prolonged hydrolysis of β-glucan and milled aspen wood by rPvCel5A forms 1365:1436 Similar effects of the mutations were observed in prolonged hydrolysis of β-glucan and milled aspen wood by rPvCel5A forms in the presence of purified β-glucosidase. 27440076 8 20 from % 1274:1274 arg1 activities 1303:1312 the activities 1299:1312 the activities 1299:1312 The N19A mutation led to a notable decrease in the specific activity against carboxymethylcellulose and barley β-glucan (by 26% and 12% relative to the rPvCel5A-wt), while the N42A and N194A mutants displayed 12-13% and 32-35% increase in the activities. 27440076 2 21 theme mutant 350:355 arg1 forms 357:361 its mutant forms 346:361 its mutant forms 346:361 In order to study the role of N-glycosylation, the wild type (wt) PvCel5A and its mutant forms, carrying Asn to Ala substitutions, were cloned into Penicillium canescens. 27440076 4 22 theme spectrometry 547:558 arg1 fingerprinting 568:581 The MALDI-TOF mass spectrometry peptide fingerprinting 528:581 The MALDI-TOF mass spectrometry peptide fingerprinting 528:581 The MALDI-TOF mass spectrometry peptide fingerprinting showed that N-glycans linked to Asn42 and Asn194 represent variable oligosaccharides, according to the formula (Man)1-9(GlcNAc)2. 27440076 7 23 theme native 1015:1020 arg1 enzyme 1022:1027 the native enzyme 1011:1027 the native enzyme 1011:1027 For N42A and N194A mutants, a slight shift of pH-optimum to pH 5.0 was observed (from pH-optimum of 4.5 for the native enzyme, rPvCel5A-wt and N19A mutant). 27440076 7 24 theme slight 933:938 arg1 shift 940:944 a slight shift 931:944 a slight shift of pH-optimum to pH 5.0 931:968 For N42A and N194A mutants, a slight shift of pH-optimum to pH 5.0 was observed (from pH-optimum of 4.5 for the native enzyme, rPvCel5A-wt and N19A mutant). 27440076 7 25 theme 4.5 1003:1005 arg1 pH-optimum 989:998 pH-optimum 989:998 pH-optimum of 4.5 for the native enzyme, rPvCel5A-wt and N19A mutant 989:1056 For N42A and N194A mutants, a slight shift of pH-optimum to pH 5.0 was observed (from pH-optimum of 4.5 for the native enzyme, rPvCel5A-wt and N19A mutant). 27440076 9 26 theme rPvCel5A 1423:1430 arg1 forms 1432:1436 rPvCel5A forms 1423:1436 rPvCel5A forms 1423:1436 Similar effects of the mutations were observed in prolonged hydrolysis of β-glucan and milled aspen wood by rPvCel5A forms in the presence of purified β-glucosidase. 27440076 8 27 theme barley 1164:1169 arg1 β-glucan 1171:1178 barley β-glucan 1164:1178 barley β-glucan (by 26% and 12% relative to the rPvCel5A-wt) 1164:1223 The N19A mutation led to a notable decrease in the specific activity against carboxymethylcellulose and barley β-glucan (by 26% and 12% relative to the rPvCel5A-wt), while the N42A and N194A mutants displayed 12-13% and 32-35% increase in the activities. 27440076 2 28 dep substitutions 384:396 arg1 to 377:378 to 377:378 to 377:378 In order to study the role of N-glycosylation, the wild type (wt) PvCel5A and its mutant forms, carrying Asn to Ala substitutions, were cloned into Penicillium canescens. 27440076 4 29 theme 1-9 699:701 arg1 GlcNAc 703:708 the formula (Man)1-9(GlcNAc)2 682:710 the formula (Man)1-9(GlcNAc)2 682:710 The MALDI-TOF mass spectrometry peptide fingerprinting showed that N-glycans linked to Asn42 and Asn194 represent variable oligosaccharides, according to the formula (Man)1-9(GlcNAc)2. 27440076 4 30 theme variable 642:649 arg1 oligosaccharides 651:666 variable oligosaccharides 642:666 variable oligosaccharides 642:666 The MALDI-TOF mass spectrometry peptide fingerprinting showed that N-glycans linked to Asn42 and Asn194 represent variable oligosaccharides, according to the formula (Man)1-9(GlcNAc)2. 27440076 0 31 theme glycosylation 19:31 arg1 Effect 0:5 Effect 0:5 Effect of N-linked glycosylation on the activity and other properties of recombinant endoglucanase IIa (Cel5A) from Penicillium verruculosum. 0:140 Effect of N-linked glycosylation on the activity and other properties of recombinant endoglucanase IIa (Cel5A) from Penicillium verruculosum. 27440076 1 32 theme N-glycosylation 220:234 arg1 Asn42 250:254 Asn42 250:254 Asn42 250:254 Endoglucanase IIa from Penicillium verruculosum (PvCel5A) has three potential N-glycosylation sites: Asn19, Asn42 and Asn194. 27440076 1 32 theme N-glycosylation 220:234 arg1 Asn19 243:247 Asn19 243:247 Asn19 243:247 Endoglucanase IIa from Penicillium verruculosum (PvCel5A) has three potential N-glycosylation sites: Asn19, Asn42 and Asn194. 27440076 1 32 theme N-glycosylation 220:234 arg1 sites 236:240 three potential N-glycosylation sites 204:240 three potential N-glycosylation sites: Asn19, Asn42 and Asn194 204:265 Endoglucanase IIa from Penicillium verruculosum (PvCel5A) has three potential N-glycosylation sites: Asn19, Asn42 and Asn194. 27440076 1 32 theme N-glycosylation 220:234 arg1 Asn194 260:265 Asn194 260:265 Asn194 260:265 Endoglucanase IIa from Penicillium verruculosum (PvCel5A) has three potential N-glycosylation sites: Asn19, Asn42 and Asn194. 27440076 9 33 located observed 1353:1360 arg1 presence 1445:1452 the presence 1441:1452 the presence of purified β-glucosidase 1441:1478 Similar effects of the mutations were observed in prolonged hydrolysis of β-glucan and milled aspen wood by rPvCel5A forms in the presence of purified β-glucosidase. 27440076 9 33 located observed 1353:1360 arg2 effects 1323:1329 Similar effects 1315:1329 Similar effects of the mutations 1315:1346 Similar effects of the mutations were observed in prolonged hydrolysis of β-glucan and milled aspen wood by rPvCel5A forms in the presence of purified β-glucosidase. 27440076 9 33 located observed 1353:1360 arg1 hydrolysis 1375:1384 prolonged hydrolysis 1365:1384 prolonged hydrolysis of β-glucan and milled aspen wood by rPvCel5A forms 1365:1436 Similar effects of the mutations were observed in prolonged hydrolysis of β-glucan and milled aspen wood by rPvCel5A forms in the presence of purified β-glucosidase. 27440076 9 34 theme β-glucosidase 1466:1478 arg1 presence 1445:1452 the presence 1441:1452 the presence of purified β-glucosidase 1441:1478 Similar effects of the mutations were observed in prolonged hydrolysis of β-glucan and milled aspen wood by rPvCel5A forms in the presence of purified β-glucosidase. 27440076 8 35 theme relative 1196:1203 arg1 % 1186:1186 26% 1184:1186 26% 1184:1186 The N19A mutation led to a notable decrease in the specific activity against carboxymethylcellulose and barley β-glucan (by 26% and 12% relative to the rPvCel5A-wt), while the N42A and N194A mutants displayed 12-13% and 32-35% increase in the activities. 27440076 2 36 theme Asn 373:375 arg1 substitutions 384:396 Asn to Ala substitutions 373:396 Asn to Ala substitutions 373:396 In order to study the role of N-glycosylation, the wild type (wt) PvCel5A and its mutant forms, carrying Asn to Ala substitutions, were cloned into Penicillium canescens. 27440076 0 37 theme N-linked 10:17 arg1 glycosylation 19:31 N-linked glycosylation 10:31 N-linked glycosylation 10:31 Effect of N-linked glycosylation on the activity and other properties of recombinant endoglucanase IIa (Cel5A) from Penicillium verruculosum. 27440076 8 38 theme N194A 1245:1249 arg1 mutants 1251:1257 the N42A and N194A mutants 1232:1257 the N42A and N194A mutants 1232:1257 The N19A mutation led to a notable decrease in the specific activity against carboxymethylcellulose and barley β-glucan (by 26% and 12% relative to the rPvCel5A-wt), while the N42A and N194A mutants displayed 12-13% and 32-35% increase in the activities. 27440076 2 39 theme Penicillium 416:426 arg1 canescens 428:436 Penicillium canescens 416:436 Penicillium canescens 416:436 In order to study the role of N-glycosylation, the wild type (wt) PvCel5A and its mutant forms, carrying Asn to Ala substitutions, were cloned into Penicillium canescens. 27440076 9 40 theme Similar 1315:1321 arg1 effects 1323:1329 Similar effects 1315:1329 Similar effects of the mutations 1315:1346 Similar effects of the mutations were observed in prolonged hydrolysis of β-glucan and milled aspen wood by rPvCel5A forms in the presence of purified β-glucosidase. 27440076 6 41 link N-linked 836:843 arg1 glycans 845:851 the N-linked glycans 832:851 the N-linked glycans 832:851 Mutations had no notable effect on the enzyme thermostability; however, the N-linked glycans stabilized the enzyme against proteolytic attack. 27440076 5 42 theme Asn19 729:733 arg1 glycosylation 735:747 Asn19 glycosylation 729:747 Asn19 glycosylation 729:747 No evidence for Asn19 glycosylation was found. 27440076 6 43 theme enzyme 799:804 arg1 thermostability 806:820 the enzyme thermostability 795:820 the enzyme thermostability 795:820 Mutations had no notable effect on the enzyme thermostability; however, the N-linked glycans stabilized the enzyme against proteolytic attack. 27440076 0 44 dep activity 40:47 arg1 the 36:38 the 36:38 the 36:38 Effect of N-linked glycosylation on the activity and other properties of recombinant endoglucanase IIa (Cel5A) from Penicillium verruculosum. 27440076 7 45 theme pH-optimum 949:958 arg1 shift 940:944 a slight shift 931:944 a slight shift of pH-optimum to pH 5.0 931:968 For N42A and N194A mutants, a slight shift of pH-optimum to pH 5.0 was observed (from pH-optimum of 4.5 for the native enzyme, rPvCel5A-wt and N19A mutant). 27440076 1 46 theme potential 210:218 arg1 Asn42 250:254 Asn42 250:254 Asn42 250:254 Endoglucanase IIa from Penicillium verruculosum (PvCel5A) has three potential N-glycosylation sites: Asn19, Asn42 and Asn194. 27440076 1 46 theme potential 210:218 arg1 Asn19 243:247 Asn19 243:247 Asn19 243:247 Endoglucanase IIa from Penicillium verruculosum (PvCel5A) has three potential N-glycosylation sites: Asn19, Asn42 and Asn194. 27440076 1 46 theme potential 210:218 arg1 sites 236:240 three potential N-glycosylation sites 204:240 three potential N-glycosylation sites: Asn19, Asn42 and Asn194 204:265 Endoglucanase IIa from Penicillium verruculosum (PvCel5A) has three potential N-glycosylation sites: Asn19, Asn42 and Asn194. 27440076 1 46 theme potential 210:218 arg1 Asn194 260:265 Asn194 260:265 Asn194 260:265 Endoglucanase IIa from Penicillium verruculosum (PvCel5A) has three potential N-glycosylation sites: Asn19, Asn42 and Asn194. 27440076 7 47 theme N19A 1046:1049 arg1 4.5 1003:1005 4.5 1003:1005 4.5 1003:1005 For N42A and N194A mutants, a slight shift of pH-optimum to pH 5.0 was observed (from pH-optimum of 4.5 for the native enzyme, rPvCel5A-wt and N19A mutant). 27440076 7 47 theme N19A 1046:1049 arg1 mutant 1051:1056 N19A mutant 1046:1056 N19A mutant 1046:1056 For N42A and N194A mutants, a slight shift of pH-optimum to pH 5.0 was observed (from pH-optimum of 4.5 for the native enzyme, rPvCel5A-wt and N19A mutant). 27440076 8 48 theme N19A 1064:1067 arg1 mutation 1069:1076 The N19A mutation 1060:1076 The N19A mutation 1060:1076 The N19A mutation led to a notable decrease in the specific activity against carboxymethylcellulose and barley β-glucan (by 26% and 12% relative to the rPvCel5A-wt), while the N42A and N194A mutants displayed 12-13% and 32-35% increase in the activities. 27440076 1 49 dep sites 236:240 arg1 Asn42 250:254 Asn42 250:254 Asn42 250:254 Endoglucanase IIa from Penicillium verruculosum (PvCel5A) has three potential N-glycosylation sites: Asn19, Asn42 and Asn194. 27440076 1 49 dep sites 236:240 arg1 Asn19 243:247 Asn19 243:247 Asn19 243:247 Endoglucanase IIa from Penicillium verruculosum (PvCel5A) has three potential N-glycosylation sites: Asn19, Asn42 and Asn194. 27440076 1 49 dep sites 236:240 arg1 sites 236:240 three potential N-glycosylation sites 204:240 three potential N-glycosylation sites: Asn19, Asn42 and Asn194 204:265 Endoglucanase IIa from Penicillium verruculosum (PvCel5A) has three potential N-glycosylation sites: Asn19, Asn42 and Asn194. 27440076 1 49 dep sites 236:240 arg1 Asn194 260:265 Asn194 260:265 Asn194 260:265 Endoglucanase IIa from Penicillium verruculosum (PvCel5A) has three potential N-glycosylation sites: Asn19, Asn42 and Asn194. 27440076 9 50 theme purified 1457:1464 arg1 β-glucosidase 1466:1478 purified β-glucosidase 1457:1478 purified β-glucosidase 1457:1478 Similar effects of the mutations were observed in prolonged hydrolysis of β-glucan and milled aspen wood by rPvCel5A forms in the presence of purified β-glucosidase. 27440076 8 51 theme N42A 1236:1239 arg1 mutants 1251:1257 the N42A and N194A mutants 1232:1257 the N42A and N194A mutants 1232:1257 The N19A mutation led to a notable decrease in the specific activity against carboxymethylcellulose and barley β-glucan (by 26% and 12% relative to the rPvCel5A-wt), while the N42A and N194A mutants displayed 12-13% and 32-35% increase in the activities. 27440076 2 52 theme wild 319:322 arg1 wt 330:331 wt 330:331 wt 330:331 In order to study the role of N-glycosylation, the wild type (wt) PvCel5A and its mutant forms, carrying Asn to Ala substitutions, were cloned into Penicillium canescens. 27440076 2 52 theme wild 319:322 arg1 type 324:327 the wild type 315:327 the wild type (wt) PvCel5A 315:340 In order to study the role of N-glycosylation, the wild type (wt) PvCel5A and its mutant forms, carrying Asn to Ala substitutions, were cloned into Penicillium canescens. 27440076 2 53 theme Ala 380:382 arg1 substitutions 384:396 Asn to Ala substitutions 373:396 Asn to Ala substitutions 373:396 In order to study the role of N-glycosylation, the wild type (wt) PvCel5A and its mutant forms, carrying Asn to Ala substitutions, were cloned into Penicillium canescens. 27440076 6 54 theme proteolytic 883:893 arg1 attack 895:900 proteolytic attack 883:900 proteolytic attack 883:900 Mutations had no notable effect on the enzyme thermostability; however, the N-linked glycans stabilized the enzyme against proteolytic attack. 27440076 4 55 attach linked 605:610 arg2 N-glycans 595:603 N-glycans 595:603 N-glycans linked to Asn42 and Asn194 595:630 The MALDI-TOF mass spectrometry peptide fingerprinting showed that N-glycans linked to Asn42 and Asn194 represent variable oligosaccharides, according to the formula (Man)1-9(GlcNAc)2. 27440076 4 55 attach linked 605:610 arg1 Asn42 615:619 Asn42 615:619 Asn42 615:619 The MALDI-TOF mass spectrometry peptide fingerprinting showed that N-glycans linked to Asn42 and Asn194 represent variable oligosaccharides, according to the formula (Man)1-9(GlcNAc)2. 27440076 4 55 attach linked 605:610 arg1 Asn194 625:630 Asn194 625:630 Asn194 625:630 The MALDI-TOF mass spectrometry peptide fingerprinting showed that N-glycans linked to Asn42 and Asn194 represent variable oligosaccharides, according to the formula (Man)1-9(GlcNAc)2. 27440076 0 56 gly glycosylation 19:31 arg1 IIa 99:101 recombinant endoglucanase IIa 73:101 recombinant endoglucanase IIa (Cel5A) 73:109 Effect of N-linked glycosylation on the activity and other properties of recombinant endoglucanase IIa (Cel5A) from Penicillium verruculosum. 27440076 0 56 gly glycosylation 19:31 arg1 Cel5A 104:108 Cel5A 104:108 Cel5A 104:108 Effect of N-linked glycosylation on the activity and other properties of recombinant endoglucanase IIa (Cel5A) from Penicillium verruculosum. 27440076 4 57 theme formula 686:692 arg1 GlcNAc 703:708 the formula (Man)1-9(GlcNAc)2 682:710 the formula (Man)1-9(GlcNAc)2 682:710 The MALDI-TOF mass spectrometry peptide fingerprinting showed that N-glycans linked to Asn42 and Asn194 represent variable oligosaccharides, according to the formula (Man)1-9(GlcNAc)2. 27440076 8 58 from increase 1287:1294 arg1 activities 1303:1312 the activities 1299:1312 the activities 1299:1312 The N19A mutation led to a notable decrease in the specific activity against carboxymethylcellulose and barley β-glucan (by 26% and 12% relative to the rPvCel5A-wt), while the N42A and N194A mutants displayed 12-13% and 32-35% increase in the activities. 27440076 8 59 theme % 1285:1285 arg1 increase 1287:1294 12-13% and 32-35% increase 1269:1294 increase 1287:1294 The N19A mutation led to a notable decrease in the specific activity against carboxymethylcellulose and barley β-glucan (by 26% and 12% relative to the rPvCel5A-wt), while the N42A and N194A mutants displayed 12-13% and 32-35% increase in the activities. 27440076 0 60 link N-linked 10:17 arg1 glycosylation 19:31 N-linked glycosylation 10:31 N-linked glycosylation 10:31 Effect of N-linked glycosylation on the activity and other properties of recombinant endoglucanase IIa (Cel5A) from Penicillium verruculosum. 27440076 7 61 dep N42A 907:910 arg1 mutants 922:928 mutants 922:928 mutants 922:928 For N42A and N194A mutants, a slight shift of pH-optimum to pH 5.0 was observed (from pH-optimum of 4.5 for the native enzyme, rPvCel5A-wt and N19A mutant). 27440076 0 62 from verruculosum 128:139 arg1 activity 40:47 activity 40:47 activity 40:47 Effect of N-linked glycosylation on the activity and other properties of recombinant endoglucanase IIa (Cel5A) from Penicillium verruculosum. 27440076 0 62 from verruculosum 128:139 arg1 properties 59:68 other properties 53:68 other properties 53:68 Effect of N-linked glycosylation on the activity and other properties of recombinant endoglucanase IIa (Cel5A) from Penicillium verruculosum. 27440076 2 63 contain carrying 364:371 arg1 forms 357:361 its mutant forms 346:361 its mutant forms 346:361 In order to study the role of N-glycosylation, the wild type (wt) PvCel5A and its mutant forms, carrying Asn to Ala substitutions, were cloned into Penicillium canescens. 27440076 2 63 contain carrying 364:371 arg2 substitutions 384:396 Asn to Ala substitutions 373:396 Asn to Ala substitutions 373:396 In order to study the role of N-glycosylation, the wild type (wt) PvCel5A and its mutant forms, carrying Asn to Ala substitutions, were cloned into Penicillium canescens. 27440076 2 64 theme N-glycosylation 298:312 arg1 role 290:293 the role 286:293 the role of N-glycosylation 286:312 In order to study the role of N-glycosylation, the wild type (wt) PvCel5A and its mutant forms, carrying Asn to Ala substitutions, were cloned into Penicillium canescens. 27440076 7 65 dep observed 974:981 arg1 pH-optimum 989:998 pH-optimum 989:998 pH-optimum of 4.5 for the native enzyme, rPvCel5A-wt and N19A mutant 989:1056 For N42A and N194A mutants, a slight shift of pH-optimum to pH 5.0 was observed (from pH-optimum of 4.5 for the native enzyme, rPvCel5A-wt and N19A mutant). 27440076 9 66 theme mutations 1338:1346 arg1 effects 1323:1329 Similar effects 1315:1329 Similar effects of the mutations 1315:1346 Similar effects of the mutations were observed in prolonged hydrolysis of β-glucan and milled aspen wood by rPvCel5A forms in the presence of purified β-glucosidase. 27440076 6 67 theme notable 777:783 arg1 effect 785:790 no notable effect 774:790 no notable effect 774:790 Mutations had no notable effect on the enzyme thermostability; however, the N-linked glycans stabilized the enzyme against proteolytic attack. 27440076 3 68 theme rPvCel5A 456:463 arg1 forms 443:447 All forms 439:447 All forms of the rPvCel5A 439:463 All forms of the rPvCel5A were successfully expressed and purified for characterization. 27440076 0 69 theme other 53:57 arg1 properties 59:68 other properties 53:68 other properties 53:68 Effect of N-linked glycosylation on the activity and other properties of recombinant endoglucanase IIa (Cel5A) from Penicillium verruculosum. 27440076 8 70 from decrease 1095:1102 arg1 activity 1120:1127 the specific activity 1107:1127 the specific activity against carboxymethylcellulose and barley β-glucan (by 26% and 12% relative to the rPvCel5A-wt) 1107:1223 The N19A mutation led to a notable decrease in the specific activity against carboxymethylcellulose and barley β-glucan (by 26% and 12% relative to the rPvCel5A-wt), while the N42A and N194A mutants displayed 12-13% and 32-35% increase in the activities. 27440076 8 71 theme notable 1087:1093 arg1 decrease 1095:1102 a notable decrease 1085:1102 a notable decrease in the specific activity against carboxymethylcellulose and barley β-glucan (by 26% and 12% relative to the rPvCel5A-wt) 1085:1223 The N19A mutation led to a notable decrease in the specific activity against carboxymethylcellulose and barley β-glucan (by 26% and 12% relative to the rPvCel5A-wt), while the N42A and N194A mutants displayed 12-13% and 32-35% increase in the activities. 27440076 1 72 theme Endoglucanase 142:154 arg1 IIa 156:158 Endoglucanase IIa 142:158 Endoglucanase IIa from Penicillium verruculosum (PvCel5A) 142:198 Endoglucanase IIa from Penicillium verruculosum (PvCel5A) has three potential N-glycosylation sites: Asn19, Asn42 and Asn194. 27217568 0 0 theme HIRA 84:87 arg1 complex 89:95 the histone chaperone HIRA complex 62:95 the histone chaperone HIRA complex 62:95 O-linked N-acetylglucosamine transferase (OGT) interacts with the histone chaperone HIRA complex and regulates nucleosome assembly and cellular senescence. 27217568 2 1 theme nucleosome 464:473 arg1 assembly 475:482 HIRA-mediated nucleosome assembly 450:482 HIRA-mediated nucleosome assembly of H3.3-H4 450:493 How HIRA-mediated nucleosome assembly of H3.3-H4 is regulated remains not well understood. 27217568 4 2 theme O-GlcNAcylation-deficient 814:838 arg1 mutant 840:845 the HIRA S231A O-GlcNAcylation-deficient mutant 799:845 the HIRA S231A O-GlcNAcylation-deficient mutant 799:845 Depletion of OGT or expression of the HIRA S231A O-GlcNAcylation-deficient mutant compromises formation of the HIRA-H3.3 complex and H3.3 nucleosome assembly. 27217568 1 3 theme histone 160:166 arg1 complex 183:189 The histone chaperone HIRA complex 156:189 The histone chaperone HIRA complex 156:189 The histone chaperone HIRA complex, consisting of histone cell cycle regulator (HIRA), Ubinuclein1 (UBN1), and calcineurin binding protein 1 (CABIN1), deposits histone variant H3.3 to genic regions and regulates gene expression in various cellular processes, including cellular senescence. 27217568 0 4 theme chaperone 74:82 arg1 complex 89:95 the histone chaperone HIRA complex 62:95 the histone chaperone HIRA complex 62:95 O-linked N-acetylglucosamine transferase (OGT) interacts with the histone chaperone HIRA complex and regulates nucleosome assembly and cellular senescence. 27217568 4 5 theme S231A 808:812 arg1 mutant 840:845 the HIRA S231A O-GlcNAcylation-deficient mutant 799:845 the HIRA S231A O-GlcNAcylation-deficient mutant 799:845 Depletion of OGT or expression of the HIRA S231A O-GlcNAcylation-deficient mutant compromises formation of the HIRA-H3.3 complex and H3.3 nucleosome assembly. 27217568 1 6 theme cellular 395:402 arg1 senescence 434:443 cellular senescence 425:443 cellular senescence 425:443 The histone chaperone HIRA complex, consisting of histone cell cycle regulator (HIRA), Ubinuclein1 (UBN1), and calcineurin binding protein 1 (CABIN1), deposits histone variant H3.3 to genic regions and regulates gene expression in various cellular processes, including cellular senescence. 27217568 1 6 theme cellular 395:402 arg1 processes 404:412 various cellular processes 387:412 various cellular processes 387:412 The histone chaperone HIRA complex, consisting of histone cell cycle regulator (HIRA), Ubinuclein1 (UBN1), and calcineurin binding protein 1 (CABIN1), deposits histone variant H3.3 to genic regions and regulates gene expression in various cellular processes, including cellular senescence. 27217568 1 7 theme chaperone 168:176 arg1 complex 183:189 The histone chaperone HIRA complex 156:189 The histone chaperone HIRA complex 156:189 The histone chaperone HIRA complex, consisting of histone cell cycle regulator (HIRA), Ubinuclein1 (UBN1), and calcineurin binding protein 1 (CABIN1), deposits histone variant H3.3 to genic regions and regulates gene expression in various cellular processes, including cellular senescence. 27217568 3 8 theme serine 657:662 arg1 O-GlcNAcylation 638:652 O-GlcNAcylation 638:652 O-GlcNAcylation of serine or threonine residues 638:684 Here, we show that O-linked N-acetylglucosamine (GlcNAc) transferase (OGT), an enzyme that catalyzes O-GlcNAcylation of serine or threonine residues, interacts with UBN1, modifies HIRA, and promotes nucleosome assembly of H3.3. 27217568 6 9 theme complex 1206:1212 arg1 formation 1214:1222 HIRA-H3.3 complex formation 1196:1222 HIRA-H3.3 complex formation 1196:1222 Taken together, these results support a model in which OGT modifies HIRA to regulate HIRA-H3.3 complex formation and H3.3 nucleosome assembly and reveal the mechanism by which OGT functions in cellular senescence. 27217568 5 10 theme OGT 937:939 arg1 depletion 941:949 OGT depletion 937:949 OGT depletion 937:949 Importantly, OGT depletion or expression of the HIRA S231A mutant delays premature cellular senescence in primary human fibroblasts, whereas overexpression of OGT accelerates senescence. 27217568 1 11 theme histone 316:322 arg1 H3.3 332:335 histone variant H3.3 316:335 histone variant H3.3 to genic regions 316:352 The histone chaperone HIRA complex, consisting of histone cell cycle regulator (HIRA), Ubinuclein1 (UBN1), and calcineurin binding protein 1 (CABIN1), deposits histone variant H3.3 to genic regions and regulates gene expression in various cellular processes, including cellular senescence. 27217568 4 12 theme mutant 840:845 arg1 Depletion 765:773 Depletion 765:773 Depletion of OGT or expression of the HIRA S231A O-GlcNAcylation-deficient mutant 765:845 Depletion of OGT or expression of the HIRA S231A O-GlcNAcylation-deficient mutant compromises formation of the HIRA-H3.3 complex and H3.3 nucleosome assembly. 27217568 5 13 from senescence 1016:1025 arg1 fibroblasts 1044:1054 primary human fibroblasts 1030:1054 primary human fibroblasts 1030:1054 Importantly, OGT depletion or expression of the HIRA S231A mutant delays premature cellular senescence in primary human fibroblasts, whereas overexpression of OGT accelerates senescence. 27217568 0 14 theme nucleosome 111:120 arg1 assembly 122:129 nucleosome assembly 111:129 nucleosome assembly 111:129 O-linked N-acetylglucosamine transferase (OGT) interacts with the histone chaperone HIRA complex and regulates nucleosome assembly and cellular senescence. 27217568 1 15 theme variant 324:330 arg1 H3.3 332:335 histone variant H3.3 316:335 histone variant H3.3 to genic regions 316:352 The histone chaperone HIRA complex, consisting of histone cell cycle regulator (HIRA), Ubinuclein1 (UBN1), and calcineurin binding protein 1 (CABIN1), deposits histone variant H3.3 to genic regions and regulates gene expression in various cellular processes, including cellular senescence. 27217568 0 16 link O-linked 0:7 arg1 transferase 29:39 O-linked N-acetylglucosamine transferase 0:39 O-linked N-acetylglucosamine transferase (OGT) 0:45 O-linked N-acetylglucosamine transferase (OGT) interacts with the histone chaperone HIRA complex and regulates nucleosome assembly and cellular senescence. 27217568 0 16 link O-linked 0:7 arg1 OGT 42:44 OGT 42:44 OGT 42:44 O-linked N-acetylglucosamine transferase (OGT) interacts with the histone chaperone HIRA complex and regulates nucleosome assembly and cellular senescence. 27217568 1 17 theme HIRA 178:181 arg1 complex 183:189 The histone chaperone HIRA complex 156:189 The histone chaperone HIRA complex 156:189 The histone chaperone HIRA complex, consisting of histone cell cycle regulator (HIRA), Ubinuclein1 (UBN1), and calcineurin binding protein 1 (CABIN1), deposits histone variant H3.3 to genic regions and regulates gene expression in various cellular processes, including cellular senescence. 27217568 2 18 theme H3.3-H4 487:493 arg1 assembly 475:482 HIRA-mediated nucleosome assembly 450:482 HIRA-mediated nucleosome assembly of H3.3-H4 450:493 How HIRA-mediated nucleosome assembly of H3.3-H4 is regulated remains not well understood. 27217568 2 19 theme HIRA-mediated 450:462 arg1 assembly 475:482 HIRA-mediated nucleosome assembly 450:482 HIRA-mediated nucleosome assembly of H3.3-H4 450:493 How HIRA-mediated nucleosome assembly of H3.3-H4 is regulated remains not well understood. 27217568 4 20 theme expression 785:794 arg1 Depletion 765:773 Depletion 765:773 Depletion of OGT or expression of the HIRA S231A O-GlcNAcylation-deficient mutant 765:845 Depletion of OGT or expression of the HIRA S231A O-GlcNAcylation-deficient mutant compromises formation of the HIRA-H3.3 complex and H3.3 nucleosome assembly. 27217568 1 21 theme cellular 425:432 arg1 senescence 434:443 cellular senescence 425:443 cellular senescence 425:443 The histone chaperone HIRA complex, consisting of histone cell cycle regulator (HIRA), Ubinuclein1 (UBN1), and calcineurin binding protein 1 (CABIN1), deposits histone variant H3.3 to genic regions and regulates gene expression in various cellular processes, including cellular senescence. 27217568 0 22 theme N-acetylglucosamine 9:27 arg1 transferase 29:39 O-linked N-acetylglucosamine transferase 0:39 O-linked N-acetylglucosamine transferase (OGT) 0:45 O-linked N-acetylglucosamine transferase (OGT) interacts with the histone chaperone HIRA complex and regulates nucleosome assembly and cellular senescence. 27217568 0 22 theme N-acetylglucosamine 9:27 arg1 OGT 42:44 OGT 42:44 OGT 42:44 O-linked N-acetylglucosamine transferase (OGT) interacts with the histone chaperone HIRA complex and regulates nucleosome assembly and cellular senescence. 27217568 1 23 from expression 373:382 arg1 senescence 434:443 cellular senescence 425:443 cellular senescence 425:443 The histone chaperone HIRA complex, consisting of histone cell cycle regulator (HIRA), Ubinuclein1 (UBN1), and calcineurin binding protein 1 (CABIN1), deposits histone variant H3.3 to genic regions and regulates gene expression in various cellular processes, including cellular senescence. 27217568 1 23 from expression 373:382 arg1 processes 404:412 various cellular processes 387:412 various cellular processes 387:412 The histone chaperone HIRA complex, consisting of histone cell cycle regulator (HIRA), Ubinuclein1 (UBN1), and calcineurin binding protein 1 (CABIN1), deposits histone variant H3.3 to genic regions and regulates gene expression in various cellular processes, including cellular senescence. 27217568 4 24 theme HIRA 803:806 arg1 mutant 840:845 the HIRA S231A O-GlcNAcylation-deficient mutant 799:845 the HIRA S231A O-GlcNAcylation-deficient mutant 799:845 Depletion of OGT or expression of the HIRA S231A O-GlcNAcylation-deficient mutant compromises formation of the HIRA-H3.3 complex and H3.3 nucleosome assembly. 27217568 5 25 theme OGT 1083:1085 arg1 overexpression 1065:1078 overexpression 1065:1078 overexpression of OGT 1065:1085 Importantly, OGT depletion or expression of the HIRA S231A mutant delays premature cellular senescence in primary human fibroblasts, whereas overexpression of OGT accelerates senescence. 27217568 0 26 theme O-linked 0:7 arg1 transferase 29:39 O-linked N-acetylglucosamine transferase 0:39 O-linked N-acetylglucosamine transferase (OGT) 0:45 O-linked N-acetylglucosamine transferase (OGT) interacts with the histone chaperone HIRA complex and regulates nucleosome assembly and cellular senescence. 27217568 0 26 theme O-linked 0:7 arg1 OGT 42:44 OGT 42:44 OGT 42:44 O-linked N-acetylglucosamine transferase (OGT) interacts with the histone chaperone HIRA complex and regulates nucleosome assembly and cellular senescence. 27217568 5 27 theme human 1038:1042 arg1 fibroblasts 1044:1054 primary human fibroblasts 1030:1054 primary human fibroblasts 1030:1054 Importantly, OGT depletion or expression of the HIRA S231A mutant delays premature cellular senescence in primary human fibroblasts, whereas overexpression of OGT accelerates senescence. 27217568 5 28 dep delays 990:995 arg1 whereas 1057:1063 whereas 1057:1063 whereas 1057:1063 Importantly, OGT depletion or expression of the HIRA S231A mutant delays premature cellular senescence in primary human fibroblasts, whereas overexpression of OGT accelerates senescence. 27217568 3 29 dep serine 657:662 arg1 residues 677:684 residues 677:684 residues 677:684 Here, we show that O-linked N-acetylglucosamine (GlcNAc) transferase (OGT), an enzyme that catalyzes O-GlcNAcylation of serine or threonine residues, interacts with UBN1, modifies HIRA, and promotes nucleosome assembly of H3.3. 27217568 4 30 theme OGT 778:780 arg1 Depletion 765:773 Depletion 765:773 Depletion of OGT or expression of the HIRA S231A O-GlcNAcylation-deficient mutant 765:845 Depletion of OGT or expression of the HIRA S231A O-GlcNAcylation-deficient mutant compromises formation of the HIRA-H3.3 complex and H3.3 nucleosome assembly. 27217568 5 31 theme mutant 983:988 arg1 depletion 941:949 OGT depletion 937:949 OGT depletion 937:949 Importantly, OGT depletion or expression of the HIRA S231A mutant delays premature cellular senescence in primary human fibroblasts, whereas overexpression of OGT accelerates senescence. 27217568 5 31 theme mutant 983:988 arg1 expression 954:963 expression 954:963 expression 954:963 Importantly, OGT depletion or expression of the HIRA S231A mutant delays premature cellular senescence in primary human fibroblasts, whereas overexpression of OGT accelerates senescence. 27217568 5 32 theme cellular 1007:1014 arg1 senescence 1016:1025 premature cellular senescence 997:1025 premature cellular senescence in primary human fibroblasts 997:1054 Importantly, OGT depletion or expression of the HIRA S231A mutant delays premature cellular senescence in primary human fibroblasts, whereas overexpression of OGT accelerates senescence. 27217568 4 33 theme complex 886:892 arg1 formation 859:867 formation 859:867 formation of the HIRA-H3.3 complex 859:892 Depletion of OGT or expression of the HIRA S231A O-GlcNAcylation-deficient mutant compromises formation of the HIRA-H3.3 complex and H3.3 nucleosome assembly. 27217568 4 33 theme complex 886:892 arg1 assembly 914:921 H3.3 nucleosome assembly 898:921 H3.3 nucleosome assembly 898:921 Depletion of OGT or expression of the HIRA S231A O-GlcNAcylation-deficient mutant compromises formation of the HIRA-H3.3 complex and H3.3 nucleosome assembly. 27217568 1 34 theme genic 340:344 arg1 regions 346:352 genic regions 340:352 genic regions 340:352 The histone chaperone HIRA complex, consisting of histone cell cycle regulator (HIRA), Ubinuclein1 (UBN1), and calcineurin binding protein 1 (CABIN1), deposits histone variant H3.3 to genic regions and regulates gene expression in various cellular processes, including cellular senescence. 27217568 1 35 theme histone 206:212 arg1 HIRA 236:239 HIRA 236:239 HIRA 236:239 The histone chaperone HIRA complex, consisting of histone cell cycle regulator (HIRA), Ubinuclein1 (UBN1), and calcineurin binding protein 1 (CABIN1), deposits histone variant H3.3 to genic regions and regulates gene expression in various cellular processes, including cellular senescence. 27217568 1 35 theme histone 206:212 arg1 regulator 225:233 histone cell cycle regulator 206:233 histone cell cycle regulator (HIRA) 206:240 The histone chaperone HIRA complex, consisting of histone cell cycle regulator (HIRA), Ubinuclein1 (UBN1), and calcineurin binding protein 1 (CABIN1), deposits histone variant H3.3 to genic regions and regulates gene expression in various cellular processes, including cellular senescence. 27217568 1 36 theme calcineurin 267:277 arg1 protein 287:293 calcineurin binding protein 1 267:295 calcineurin binding protein 1 (CABIN1) 267:304 The histone chaperone HIRA complex, consisting of histone cell cycle regulator (HIRA), Ubinuclein1 (UBN1), and calcineurin binding protein 1 (CABIN1), deposits histone variant H3.3 to genic regions and regulates gene expression in various cellular processes, including cellular senescence. 27217568 1 36 theme calcineurin 267:277 arg1 CABIN1 298:303 CABIN1 298:303 CABIN1 298:303 The histone chaperone HIRA complex, consisting of histone cell cycle regulator (HIRA), Ubinuclein1 (UBN1), and calcineurin binding protein 1 (CABIN1), deposits histone variant H3.3 to genic regions and regulates gene expression in various cellular processes, including cellular senescence. 27217568 4 37 theme nucleosome 903:912 arg1 assembly 914:921 H3.3 nucleosome assembly 898:921 H3.3 nucleosome assembly 898:921 Depletion of OGT or expression of the HIRA S231A O-GlcNAcylation-deficient mutant compromises formation of the HIRA-H3.3 complex and H3.3 nucleosome assembly. 27217568 3 38 theme N-acetylglucosamine 565:583 arg1 OGT 607:609 OGT 607:609 OGT 607:609 Here, we show that O-linked N-acetylglucosamine (GlcNAc) transferase (OGT), an enzyme that catalyzes O-GlcNAcylation of serine or threonine residues, interacts with UBN1, modifies HIRA, and promotes nucleosome assembly of H3.3. 27217568 3 38 theme N-acetylglucosamine 565:583 arg1 transferase 594:604 O-linked N-acetylglucosamine (GlcNAc) transferase 556:604 O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) 556:610 Here, we show that O-linked N-acetylglucosamine (GlcNAc) transferase (OGT), an enzyme that catalyzes O-GlcNAcylation of serine or threonine residues, interacts with UBN1, modifies HIRA, and promotes nucleosome assembly of H3.3. 27217568 3 38 theme N-acetylglucosamine 565:583 arg1 enzyme 616:621 an enzyme 613:621 an enzyme that catalyzes O-GlcNAcylation of serine or threonine residues 613:684 Here, we show that O-linked N-acetylglucosamine (GlcNAc) transferase (OGT), an enzyme that catalyzes O-GlcNAcylation of serine or threonine residues, interacts with UBN1, modifies HIRA, and promotes nucleosome assembly of H3.3. 27217568 1 39 theme cell 214:217 arg1 HIRA 236:239 HIRA 236:239 HIRA 236:239 The histone chaperone HIRA complex, consisting of histone cell cycle regulator (HIRA), Ubinuclein1 (UBN1), and calcineurin binding protein 1 (CABIN1), deposits histone variant H3.3 to genic regions and regulates gene expression in various cellular processes, including cellular senescence. 27217568 1 39 theme cell 214:217 arg1 regulator 225:233 histone cell cycle regulator 206:233 histone cell cycle regulator (HIRA) 206:240 The histone chaperone HIRA complex, consisting of histone cell cycle regulator (HIRA), Ubinuclein1 (UBN1), and calcineurin binding protein 1 (CABIN1), deposits histone variant H3.3 to genic regions and regulates gene expression in various cellular processes, including cellular senescence. 27217568 3 40 link O-linked 556:563 arg1 N-acetylglucosamine 565:583 O-linked N-acetylglucosamine 556:583 O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) 556:610 Here, we show that O-linked N-acetylglucosamine (GlcNAc) transferase (OGT), an enzyme that catalyzes O-GlcNAcylation of serine or threonine residues, interacts with UBN1, modifies HIRA, and promotes nucleosome assembly of H3.3. 27217568 3 40 link O-linked 556:563 arg1 GlcNAc 586:591 GlcNAc 586:591 GlcNAc 586:591 Here, we show that O-linked N-acetylglucosamine (GlcNAc) transferase (OGT), an enzyme that catalyzes O-GlcNAcylation of serine or threonine residues, interacts with UBN1, modifies HIRA, and promotes nucleosome assembly of H3.3. 27217568 1 41 theme binding 279:285 arg1 protein 287:293 calcineurin binding protein 1 267:295 calcineurin binding protein 1 (CABIN1) 267:304 The histone chaperone HIRA complex, consisting of histone cell cycle regulator (HIRA), Ubinuclein1 (UBN1), and calcineurin binding protein 1 (CABIN1), deposits histone variant H3.3 to genic regions and regulates gene expression in various cellular processes, including cellular senescence. 27217568 1 41 theme binding 279:285 arg1 CABIN1 298:303 CABIN1 298:303 CABIN1 298:303 The histone chaperone HIRA complex, consisting of histone cell cycle regulator (HIRA), Ubinuclein1 (UBN1), and calcineurin binding protein 1 (CABIN1), deposits histone variant H3.3 to genic regions and regulates gene expression in various cellular processes, including cellular senescence. 27217568 0 42 theme cellular 135:142 arg1 senescence 144:153 cellular senescence 135:153 cellular senescence 135:153 O-linked N-acetylglucosamine transferase (OGT) interacts with the histone chaperone HIRA complex and regulates nucleosome assembly and cellular senescence. 27217568 1 43 theme cycle 219:223 arg1 HIRA 236:239 HIRA 236:239 HIRA 236:239 The histone chaperone HIRA complex, consisting of histone cell cycle regulator (HIRA), Ubinuclein1 (UBN1), and calcineurin binding protein 1 (CABIN1), deposits histone variant H3.3 to genic regions and regulates gene expression in various cellular processes, including cellular senescence. 27217568 1 43 theme cycle 219:223 arg1 regulator 225:233 histone cell cycle regulator 206:233 histone cell cycle regulator (HIRA) 206:240 The histone chaperone HIRA complex, consisting of histone cell cycle regulator (HIRA), Ubinuclein1 (UBN1), and calcineurin binding protein 1 (CABIN1), deposits histone variant H3.3 to genic regions and regulates gene expression in various cellular processes, including cellular senescence. 27217568 3 44 theme nucleosome 736:745 arg1 assembly 747:754 nucleosome assembly 736:754 nucleosome assembly of H3.3 736:762 Here, we show that O-linked N-acetylglucosamine (GlcNAc) transferase (OGT), an enzyme that catalyzes O-GlcNAcylation of serine or threonine residues, interacts with UBN1, modifies HIRA, and promotes nucleosome assembly of H3.3. 27217568 5 45 theme premature 997:1005 arg1 senescence 1016:1025 premature cellular senescence 997:1025 premature cellular senescence in primary human fibroblasts 997:1054 Importantly, OGT depletion or expression of the HIRA S231A mutant delays premature cellular senescence in primary human fibroblasts, whereas overexpression of OGT accelerates senescence. 27217568 6 46 theme H3.3 1228:1231 arg1 assembly 1244:1251 H3.3 nucleosome assembly 1228:1251 H3.3 nucleosome assembly 1228:1251 Taken together, these results support a model in which OGT modifies HIRA to regulate HIRA-H3.3 complex formation and H3.3 nucleosome assembly and reveal the mechanism by which OGT functions in cellular senescence. 27217568 4 47 theme H3.3 898:901 arg1 assembly 914:921 H3.3 nucleosome assembly 898:921 H3.3 nucleosome assembly 898:921 Depletion of OGT or expression of the HIRA S231A O-GlcNAcylation-deficient mutant compromises formation of the HIRA-H3.3 complex and H3.3 nucleosome assembly. 27217568 1 48 theme gene 368:371 arg1 expression 373:382 gene expression 368:382 gene expression in various cellular processes, including cellular senescence 368:443 The histone chaperone HIRA complex, consisting of histone cell cycle regulator (HIRA), Ubinuclein1 (UBN1), and calcineurin binding protein 1 (CABIN1), deposits histone variant H3.3 to genic regions and regulates gene expression in various cellular processes, including cellular senescence. 27217568 3 49 theme O-linked 556:563 arg1 N-acetylglucosamine 565:583 O-linked N-acetylglucosamine 556:583 O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) 556:610 Here, we show that O-linked N-acetylglucosamine (GlcNAc) transferase (OGT), an enzyme that catalyzes O-GlcNAcylation of serine or threonine residues, interacts with UBN1, modifies HIRA, and promotes nucleosome assembly of H3.3. 27217568 3 49 theme O-linked 556:563 arg1 GlcNAc 586:591 GlcNAc 586:591 GlcNAc 586:591 Here, we show that O-linked N-acetylglucosamine (GlcNAc) transferase (OGT), an enzyme that catalyzes O-GlcNAcylation of serine or threonine residues, interacts with UBN1, modifies HIRA, and promotes nucleosome assembly of H3.3. 27217568 6 50 theme HIRA-H3.3 1196:1204 arg1 formation 1214:1222 HIRA-H3.3 complex formation 1196:1222 HIRA-H3.3 complex formation 1196:1222 Taken together, these results support a model in which OGT modifies HIRA to regulate HIRA-H3.3 complex formation and H3.3 nucleosome assembly and reveal the mechanism by which OGT functions in cellular senescence. 27217568 6 51 theme nucleosome 1233:1242 arg1 assembly 1244:1251 H3.3 nucleosome assembly 1228:1251 H3.3 nucleosome assembly 1228:1251 Taken together, these results support a model in which OGT modifies HIRA to regulate HIRA-H3.3 complex formation and H3.3 nucleosome assembly and reveal the mechanism by which OGT functions in cellular senescence. 27217568 6 52 theme cellular 1304:1311 arg1 senescence 1313:1322 cellular senescence 1304:1322 cellular senescence 1304:1322 Taken together, these results support a model in which OGT modifies HIRA to regulate HIRA-H3.3 complex formation and H3.3 nucleosome assembly and reveal the mechanism by which OGT functions in cellular senescence. 27217568 3 53 theme H3.3 759:762 arg1 assembly 747:754 nucleosome assembly 736:754 nucleosome assembly of H3.3 736:762 Here, we show that O-linked N-acetylglucosamine (GlcNAc) transferase (OGT), an enzyme that catalyzes O-GlcNAcylation of serine or threonine residues, interacts with UBN1, modifies HIRA, and promotes nucleosome assembly of H3.3. 27217568 5 54 theme primary 1030:1036 arg1 fibroblasts 1044:1054 primary human fibroblasts 1030:1054 primary human fibroblasts 1030:1054 Importantly, OGT depletion or expression of the HIRA S231A mutant delays premature cellular senescence in primary human fibroblasts, whereas overexpression of OGT accelerates senescence. 27217568 0 55 theme histone 66:72 arg1 complex 89:95 the histone chaperone HIRA complex 62:95 the histone chaperone HIRA complex 62:95 O-linked N-acetylglucosamine transferase (OGT) interacts with the histone chaperone HIRA complex and regulates nucleosome assembly and cellular senescence. 27217568 1 56 theme various 387:393 arg1 senescence 434:443 cellular senescence 425:443 cellular senescence 425:443 The histone chaperone HIRA complex, consisting of histone cell cycle regulator (HIRA), Ubinuclein1 (UBN1), and calcineurin binding protein 1 (CABIN1), deposits histone variant H3.3 to genic regions and regulates gene expression in various cellular processes, including cellular senescence. 27217568 1 56 theme various 387:393 arg1 processes 404:412 various cellular processes 387:412 various cellular processes 387:412 The histone chaperone HIRA complex, consisting of histone cell cycle regulator (HIRA), Ubinuclein1 (UBN1), and calcineurin binding protein 1 (CABIN1), deposits histone variant H3.3 to genic regions and regulates gene expression in various cellular processes, including cellular senescence. 27217568 5 57 theme HIRA 972:975 arg1 mutant 983:988 the HIRA S231A mutant 968:988 the HIRA S231A mutant 968:988 Importantly, OGT depletion or expression of the HIRA S231A mutant delays premature cellular senescence in primary human fibroblasts, whereas overexpression of OGT accelerates senescence. 27217568 5 58 theme S231A 977:981 arg1 mutant 983:988 the HIRA S231A mutant 968:988 the HIRA S231A mutant 968:988 Importantly, OGT depletion or expression of the HIRA S231A mutant delays premature cellular senescence in primary human fibroblasts, whereas overexpression of OGT accelerates senescence. 27217568 3 59 theme threonine 667:675 arg1 O-GlcNAcylation 638:652 O-GlcNAcylation 638:652 O-GlcNAcylation of serine or threonine residues 638:684 Here, we show that O-linked N-acetylglucosamine (GlcNAc) transferase (OGT), an enzyme that catalyzes O-GlcNAcylation of serine or threonine residues, interacts with UBN1, modifies HIRA, and promotes nucleosome assembly of H3.3. 26184710 4 0 theme general 630:636 arg1 release 638:644 general release 630:644 general release of O-linked saccharides from glycoproteins 630:687 This fact is probably due to the absence of an enzyme for general release of O-linked saccharides from glycoproteins and due to their low ionization yield in mass spectrometry (MS). 26184710 1 1 attach attached 183:190 arg1 proteins 195:202 proteins 195:202 proteins 195:202 Investigation of oligosaccharides attached to proteins as post-translational modification remains an important research field in the area of glycoproteomics as well as in biotechnology. 26184710 1 1 attach attached 183:190 arg2 oligosaccharides 166:181 oligosaccharides 166:181 oligosaccharides attached to proteins as post-translational modification 166:237 Investigation of oligosaccharides attached to proteins as post-translational modification remains an important research field in the area of glycoproteomics as well as in biotechnology. 26184710 0 2 with labeling 92:99 arg1 1-phenyl-3-methyl-5-pyrazolone 117:146 deuterated 1-phenyl-3-methyl-5-pyrazolone 106:146 deuterated 1-phenyl-3-methyl-5-pyrazolone 106:146 Quantitative fingerprinting of O-linked glycans released from proteins using isotopic coded labeling with deuterated 1-phenyl-3-methyl-5-pyrazolone. 26184710 2 3 theme glycans 409:415 arg1 analysis 397:404 qualitative and quantitative analysis 368:404 qualitative and quantitative analysis of glycans 368:415 The development of new tools for qualitative and quantitative analysis of glycans has gained high importance in recent years. 26184710 11 4 theme profiles 1674:1681 arg1 determination 1648:1660 the determination 1644:1660 the determination of O-glycan profiles in mixtures 1644:1693 For the determination of O-glycan profiles in mixtures, a HPLC separation was combined with a high resolution Qq-oaTOF instrument. 26184710 13 5 theme clusters 1985:1992 arg1 presence 1958:1965 the presence 1954:1965 the presence of various sodium clusters in the MS spectrum 1954:2011 This separation step was particularly useful for removing of salts avoiding so the presence of various sodium clusters in the MS spectrum. 26184710 13 6 attach presence 1958:1965 arg1 spectrum 2004:2011 the MS spectrum 1997:2011 the MS spectrum 1997:2011 This separation step was particularly useful for removing of salts avoiding so the presence of various sodium clusters in the MS spectrum. 26184710 13 6 attach presence 1958:1965 arg2 clusters 1985:1992 various sodium clusters 1970:1992 various sodium clusters 1970:1992 This separation step was particularly useful for removing of salts avoiding so the presence of various sodium clusters in the MS spectrum. 26184710 12 7 theme RP-type 1771:1777 arg1 phases 1790:1795 RP-type stationary phases 1771:1795 RP-type stationary phases 1771:1795 RP-type stationary phases were successful in separating glycan species including some of isomeric ones. 26184710 4 8 theme ionization 710:719 arg1 yield 721:725 their low ionization yield 700:725 their low ionization yield in mass spectrometry (MS) 700:751 This fact is probably due to the absence of an enzyme for general release of O-linked saccharides from glycoproteins and due to their low ionization yield in mass spectrometry (MS). 26184710 1 9 theme important 250:258 arg1 field 269:273 an important research field 247:273 an important research field 247:273 Investigation of oligosaccharides attached to proteins as post-translational modification remains an important research field in the area of glycoproteomics as well as in biotechnology. 26184710 13 10 theme various 1970:1976 arg1 clusters 1985:1992 various sodium clusters 1970:1992 various sodium clusters 1970:1992 This separation step was particularly useful for removing of salts avoiding so the presence of various sodium clusters in the MS spectrum. 26184710 10 11 theme abundant 1601:1608 arg1 values 1613:1618 very low abundant CV values 1592:1618 very low abundant CV values between 15 and 20% 1592:1637 For higher abundant O-glycans a mean coefficient of variation (CV) less than 6% could be attained, for very low abundant CV values between 15 and 20%. 26184710 2 12 theme new 354:356 arg1 tools 358:362 new tools 354:362 new tools for qualitative and quantitative analysis of glycans 354:415 The development of new tools for qualitative and quantitative analysis of glycans has gained high importance in recent years. 26184710 5 13 theme mucin-type 852:861 arg1 O-glycans 863:871 mucin-type O-glycans 852:871 mucin-type O-glycans 852:871 In this paper, a method is established aimed at improved qualitative and quantitative analysis of mucin-type O-glycans. 26184710 7 14 theme coded 1079:1083 arg1 labeling 1085:1092 stable-isotope coded labeling 1064:1092 stable-isotope coded labeling by d0/d5 1-phenyl-3-methyl-5-pyrazolidone (PMP) 1064:1140 For the purpose of improved quantitative analysis, stable-isotope coded labeling by d0/d5 1-phenyl-3-methyl-5-pyrazolidone (PMP) was performed. 26184710 6 15 theme spectrometric 983:995 arg1 quantification 997:1010 mass spectrometric quantification 978:1010 mass spectrometric quantification 978:1010 A chemical reaction combining release and derivatization of O-glycans in one step is combined here with mass spectrometric quantification. 26184710 10 16 dep % 1567:1567 arg1 6 1566:1566 6 1566:1566 6 1566:1566 For higher abundant O-glycans a mean coefficient of variation (CV) less than 6% could be attained, for very low abundant CV values between 15 and 20%. 26184710 11 17 theme resolution 1739:1748 arg1 instrument 1759:1768 a high resolution Qq-oaTOF instrument 1732:1768 a high resolution Qq-oaTOF instrument 1732:1768 For the determination of O-glycan profiles in mixtures, a HPLC separation was combined with a high resolution Qq-oaTOF instrument. 26184710 7 18 theme d0/d5 1097:1101 arg1 1-phenyl-3-methyl-5-pyrazolidone 1103:1134 d0/d5 1-phenyl-3-methyl-5-pyrazolidone 1097:1134 d0/d5 1-phenyl-3-methyl-5-pyrazolidone (PMP) 1097:1140 For the purpose of improved quantitative analysis, stable-isotope coded labeling by d0/d5 1-phenyl-3-methyl-5-pyrazolidone (PMP) was performed. 26184710 7 18 theme d0/d5 1097:1101 arg1 PMP 1137:1139 PMP 1137:1139 PMP 1137:1139 For the purpose of improved quantitative analysis, stable-isotope coded labeling by d0/d5 1-phenyl-3-methyl-5-pyrazolidone (PMP) was performed. 26184710 7 19 theme quantitative 1041:1052 arg1 analysis 1054:1061 improved quantitative analysis 1032:1061 improved quantitative analysis 1032:1061 For the purpose of improved quantitative analysis, stable-isotope coded labeling by d0/d5 1-phenyl-3-methyl-5-pyrazolidone (PMP) was performed. 26184710 10 20 theme abundant 1500:1507 arg1 O-glycans 1509:1517 higher abundant O-glycans 1493:1517 higher abundant O-glycans 1493:1517 For higher abundant O-glycans a mean coefficient of variation (CV) less than 6% could be attained, for very low abundant CV values between 15 and 20%. 26184710 0 21 theme coded 86:90 arg1 labeling 92:99 isotopic coded labeling 77:99 isotopic coded labeling with deuterated 1-phenyl-3-methyl-5-pyrazolone 77:146 Quantitative fingerprinting of O-linked glycans released from proteins using isotopic coded labeling with deuterated 1-phenyl-3-methyl-5-pyrazolone. 26184710 1 22 theme post-translational 207:224 arg1 modification 226:237 post-translational modification 207:237 post-translational modification 207:237 Investigation of oligosaccharides attached to proteins as post-translational modification remains an important research field in the area of glycoproteomics as well as in biotechnology. 26184710 11 23 from mixtures 1686:1693 arg1 determination 1648:1660 the determination 1644:1660 the determination of O-glycan profiles in mixtures 1644:1693 For the determination of O-glycan profiles in mixtures, a HPLC separation was combined with a high resolution Qq-oaTOF instrument. 26184710 9 24 theme ionization 1357:1366 arg1 yields 1368:1373 ionization yields 1357:1373 ionization yields in MS. By introducing an internal standard (e.g. GlcNAc3) the reproducibility for quantification can be improved 1357:1486 Beneath improving the reproducibility of quantitation, PMP derivatization contributed to an enhancement of ionization yields in MS. By introducing an internal standard (e.g. GlcNAc3) the reproducibility for quantification can be improved. 26184710 9 25 dep GlcNAc3 1424:1430 arg1 e.g. 1419:1422 e.g. 1419:1422 e.g. 1419:1422 Beneath improving the reproducibility of quantitation, PMP derivatization contributed to an enhancement of ionization yields in MS. By introducing an internal standard (e.g. GlcNAc3) the reproducibility for quantification can be improved. 26184710 0 26 theme isotopic 77:84 arg1 labeling 92:99 isotopic coded labeling 77:99 isotopic coded labeling with deuterated 1-phenyl-3-methyl-5-pyrazolone 77:146 Quantitative fingerprinting of O-linked glycans released from proteins using isotopic coded labeling with deuterated 1-phenyl-3-methyl-5-pyrazolone. 26184710 0 27 theme Quantitative 0:11 arg1 fingerprinting 13:26 Quantitative fingerprinting 0:26 Quantitative fingerprinting of O-linked glycans 0:46 Quantitative fingerprinting of O-linked glycans released from proteins using isotopic coded labeling with deuterated 1-phenyl-3-methyl-5-pyrazolone. 26184710 11 28 from profiles 1674:1681 arg1 mixtures 1686:1693 mixtures 1686:1693 mixtures 1686:1693 For the determination of O-glycan profiles in mixtures, a HPLC separation was combined with a high resolution Qq-oaTOF instrument. 26184710 5 29 theme O-glycans 863:871 arg1 analysis 840:847 improved qualitative and quantitative analysis 802:847 improved qualitative and quantitative analysis of mucin-type O-glycans 802:871 In this paper, a method is established aimed at improved qualitative and quantitative analysis of mucin-type O-glycans. 26184710 10 30 theme variation 1541:1549 arg1 coefficient 1526:1536 a mean coefficient 1519:1536 a mean coefficient of variation (CV) less than 6% 1519:1567 For higher abundant O-glycans a mean coefficient of variation (CV) less than 6% could be attained, for very low abundant CV values between 15 and 20%. 26184710 11 31 theme HPLC 1698:1701 arg1 separation 1703:1712 a HPLC separation 1696:1712 a HPLC separation 1696:1712 For the determination of O-glycan profiles in mixtures, a HPLC separation was combined with a high resolution Qq-oaTOF instrument. 26184710 0 32 theme glycans 40:46 arg1 fingerprinting 13:26 Quantitative fingerprinting 0:26 Quantitative fingerprinting of O-linked glycans 0:46 Quantitative fingerprinting of O-linked glycans released from proteins using isotopic coded labeling with deuterated 1-phenyl-3-methyl-5-pyrazolone. 26184710 5 33 theme qualitative 811:821 arg1 analysis 840:847 improved qualitative and quantitative analysis 802:847 improved qualitative and quantitative analysis of mucin-type O-glycans 802:871 In this paper, a method is established aimed at improved qualitative and quantitative analysis of mucin-type O-glycans. 26184710 12 34 theme glycan 1827:1832 arg1 some 1852:1855 some 1852:1855 some 1852:1855 RP-type stationary phases were successful in separating glycan species including some of isomeric ones. 26184710 12 34 theme glycan 1827:1832 arg1 ones 1869:1872 isomeric ones 1860:1872 isomeric ones 1860:1872 RP-type stationary phases were successful in separating glycan species including some of isomeric ones. 26184710 12 34 theme glycan 1827:1832 arg1 species 1834:1840 separating glycan species 1816:1840 separating glycan species including some of isomeric ones 1816:1872 RP-type stationary phases were successful in separating glycan species including some of isomeric ones. 26184710 5 35 theme quantitative 827:838 arg1 analysis 840:847 improved qualitative and quantitative analysis 802:847 improved qualitative and quantitative analysis of mucin-type O-glycans 802:871 In this paper, a method is established aimed at improved qualitative and quantitative analysis of mucin-type O-glycans. 26184710 12 36 from species 1834:1840 arg1 successful 1802:1811 successful 1802:1811 successful 1802:1811 RP-type stationary phases were successful in separating glycan species including some of isomeric ones. 26184710 2 37 theme quantitative 384:395 arg1 analysis 397:404 qualitative and quantitative analysis 368:404 qualitative and quantitative analysis of glycans 368:415 The development of new tools for qualitative and quantitative analysis of glycans has gained high importance in recent years. 26184710 12 38 theme isomeric 1860:1867 arg1 ones 1869:1872 isomeric ones 1860:1872 isomeric ones 1860:1872 RP-type stationary phases were successful in separating glycan species including some of isomeric ones. 26184710 4 39 theme O-linked 649:656 arg1 saccharides 658:668 O-linked saccharides 649:668 O-linked saccharides 649:668 This fact is probably due to the absence of an enzyme for general release of O-linked saccharides from glycoproteins and due to their low ionization yield in mass spectrometry (MS). 26184710 13 40 theme MS 2001:2002 arg1 spectrum 2004:2011 the MS spectrum 1997:2011 the MS spectrum 1997:2011 This separation step was particularly useful for removing of salts avoiding so the presence of various sodium clusters in the MS spectrum. 26184710 2 41 theme high 428:431 arg1 importance 433:442 high importance 428:442 high importance 428:442 The development of new tools for qualitative and quantitative analysis of glycans has gained high importance in recent years. 26184710 1 42 theme glycoproteomics 290:304 arg1 area 282:285 the area 278:285 the area of glycoproteomics 278:304 Investigation of oligosaccharides attached to proteins as post-translational modification remains an important research field in the area of glycoproteomics as well as in biotechnology. 26184710 6 43 from release 904:910 arg1 step 951:954 one step 947:954 one step 947:954 A chemical reaction combining release and derivatization of O-glycans in one step is combined here with mass spectrometric quantification. 26184710 0 44 link O-linked 31:38 arg1 glycans 40:46 O-linked glycans 31:46 O-linked glycans 31:46 Quantitative fingerprinting of O-linked glycans released from proteins using isotopic coded labeling with deuterated 1-phenyl-3-methyl-5-pyrazolone. 26184710 10 45 theme low 1597:1599 arg1 values 1613:1618 very low abundant CV values 1592:1618 very low abundant CV values between 15 and 20% 1592:1637 For higher abundant O-glycans a mean coefficient of variation (CV) less than 6% could be attained, for very low abundant CV values between 15 and 20%. 26184710 13 46 theme sodium 1978:1983 arg1 clusters 1985:1992 various sodium clusters 1970:1992 various sodium clusters 1970:1992 This separation step was particularly useful for removing of salts avoiding so the presence of various sodium clusters in the MS spectrum. 26184710 12 47 theme stationary 1779:1788 arg1 phases 1790:1795 RP-type stationary phases 1771:1795 RP-type stationary phases 1771:1795 RP-type stationary phases were successful in separating glycan species including some of isomeric ones. 26184710 4 48 from yield 721:725 arg1 MS 749:750 MS 749:750 MS 749:750 This fact is probably due to the absence of an enzyme for general release of O-linked saccharides from glycoproteins and due to their low ionization yield in mass spectrometry (MS). 26184710 4 48 from yield 721:725 arg1 spectrometry 735:746 mass spectrometry 730:746 mass spectrometry (MS) 730:751 This fact is probably due to the absence of an enzyme for general release of O-linked saccharides from glycoproteins and due to their low ionization yield in mass spectrometry (MS). 26184710 8 49 theme -PMP 1210:1213 arg1 -version 1168:1175 The "heavy"-version 1157:1175 The "heavy"-version 1157:1175 The "heavy"-version of this label, penta-deutero (d5)-PMP, was synthesized for this purpose. 26184710 6 50 theme O-glycans 934:942 arg1 release 904:910 release 904:910 release 904:910 A chemical reaction combining release and derivatization of O-glycans in one step is combined here with mass spectrometric quantification. 26184710 6 50 theme O-glycans 934:942 arg1 derivatization 916:929 derivatization 916:929 derivatization 916:929 A chemical reaction combining release and derivatization of O-glycans in one step is combined here with mass spectrometric quantification. 26184710 4 51 theme low 706:708 arg1 yield 721:725 their low ionization yield 700:725 their low ionization yield in mass spectrometry (MS) 700:751 This fact is probably due to the absence of an enzyme for general release of O-linked saccharides from glycoproteins and due to their low ionization yield in mass spectrometry (MS). 26184710 8 52 dep this 1180:1183 arg1 label 1185:1189 label 1185:1189 label 1185:1189 The "heavy"-version of this label, penta-deutero (d5)-PMP, was synthesized for this purpose. 26184710 11 53 theme O-glycan 1665:1672 arg1 profiles 1674:1681 O-glycan profiles 1665:1681 O-glycan profiles in mixtures 1665:1693 For the determination of O-glycan profiles in mixtures, a HPLC separation was combined with a high resolution Qq-oaTOF instrument. 26184710 3 54 from underrepresented 540:555 arg1 literature 560:569 literature 560:569 literature 560:569 This is particularly true with O-glycans for which quantitative data are still underrepresented in literature. 26184710 2 55 theme qualitative 368:378 arg1 analysis 397:404 qualitative and quantitative analysis 368:404 qualitative and quantitative analysis of glycans 368:415 The development of new tools for qualitative and quantitative analysis of glycans has gained high importance in recent years. 26184710 6 56 from derivatization 916:929 arg1 step 951:954 one step 947:954 one step 947:954 A chemical reaction combining release and derivatization of O-glycans in one step is combined here with mass spectrometric quantification. 26184710 3 57 from literature 560:569 arg1 underrepresented 540:555 underrepresented 540:555 underrepresented 540:555 This is particularly true with O-glycans for which quantitative data are still underrepresented in literature. 26184710 2 58 theme tools 358:362 arg1 development 339:349 The development 335:349 The development of new tools for qualitative and quantitative analysis of glycans 335:415 The development of new tools for qualitative and quantitative analysis of glycans has gained high importance in recent years. 26184710 1 59 theme research 260:267 arg1 field 269:273 an important research field 247:273 an important research field 247:273 Investigation of oligosaccharides attached to proteins as post-translational modification remains an important research field in the area of glycoproteomics as well as in biotechnology. 26184710 5 60 dep established 781:791 arg1 aimed 793:797 aimed 793:797 is established aimed at improved qualitative and quantitative analysis of mucin-type O-glycans 778:871 In this paper, a method is established aimed at improved qualitative and quantitative analysis of mucin-type O-glycans. 26184710 10 61 theme CV 1610:1611 arg1 values 1613:1618 very low abundant CV values 1592:1618 very low abundant CV values between 15 and 20% 1592:1637 For higher abundant O-glycans a mean coefficient of variation (CV) less than 6% could be attained, for very low abundant CV values between 15 and 20%. 26184710 10 62 dep variation 1541:1549 arg1 % 1567:1567 % 1567:1567 % 1567:1567 For higher abundant O-glycans a mean coefficient of variation (CV) less than 6% could be attained, for very low abundant CV values between 15 and 20%. 26184710 3 63 with true 482:485 arg1 O-glycans 492:500 O-glycans 492:500 O-glycans for which quantitative data are still underrepresented in literature 492:569 This is particularly true with O-glycans for which quantitative data are still underrepresented in literature. 26184710 9 64 theme quantitation 1291:1302 arg1 reproducibility 1272:1286 the reproducibility 1268:1286 the reproducibility of quantitation 1268:1302 Beneath improving the reproducibility of quantitation, PMP derivatization contributed to an enhancement of ionization yields in MS. By introducing an internal standard (e.g. GlcNAc3) the reproducibility for quantification can be improved. 26184710 13 65 from presence 1958:1965 arg1 spectrum 2004:2011 the MS spectrum 1997:2011 the MS spectrum 1997:2011 This separation step was particularly useful for removing of salts avoiding so the presence of various sodium clusters in the MS spectrum. 26184710 6 66 theme mass 978:981 arg1 quantification 997:1010 mass spectrometric quantification 978:1010 mass spectrometric quantification 978:1010 A chemical reaction combining release and derivatization of O-glycans in one step is combined here with mass spectrometric quantification. 26184710 9 67 theme PMP 1305:1307 arg1 derivatization 1309:1322 PMP derivatization 1305:1322 PMP derivatization 1305:1322 Beneath improving the reproducibility of quantitation, PMP derivatization contributed to an enhancement of ionization yields in MS. By introducing an internal standard (e.g. GlcNAc3) the reproducibility for quantification can be improved. 26184710 7 68 theme stable-isotope 1064:1077 arg1 labeling 1085:1092 stable-isotope coded labeling 1064:1092 stable-isotope coded labeling by d0/d5 1-phenyl-3-methyl-5-pyrazolidone (PMP) 1064:1140 For the purpose of improved quantitative analysis, stable-isotope coded labeling by d0/d5 1-phenyl-3-methyl-5-pyrazolidone (PMP) was performed. 26184710 1 69 theme oligosaccharides 166:181 arg1 Investigation 149:161 Investigation 149:161 Investigation of oligosaccharides attached to proteins as post-translational modification 149:237 Investigation of oligosaccharides attached to proteins as post-translational modification remains an important research field in the area of glycoproteomics as well as in biotechnology. 26184710 11 70 theme Qq-oaTOF 1750:1757 arg1 instrument 1759:1768 a high resolution Qq-oaTOF instrument 1732:1768 a high resolution Qq-oaTOF instrument 1732:1768 For the determination of O-glycan profiles in mixtures, a HPLC separation was combined with a high resolution Qq-oaTOF instrument. 26184710 4 71 from glycoproteins 675:687 arg1 release 638:644 general release 630:644 general release of O-linked saccharides from glycoproteins 630:687 This fact is probably due to the absence of an enzyme for general release of O-linked saccharides from glycoproteins and due to their low ionization yield in mass spectrometry (MS). 26184710 7 72 theme analysis 1054:1061 arg1 purpose 1021:1027 the purpose 1017:1027 the purpose of improved quantitative analysis 1017:1061 For the purpose of improved quantitative analysis, stable-isotope coded labeling by d0/d5 1-phenyl-3-methyl-5-pyrazolidone (PMP) was performed. 26184710 4 73 theme mass 730:733 arg1 MS 749:750 MS 749:750 MS 749:750 This fact is probably due to the absence of an enzyme for general release of O-linked saccharides from glycoproteins and due to their low ionization yield in mass spectrometry (MS). 26184710 4 73 theme mass 730:733 arg1 spectrometry 735:746 mass spectrometry 730:746 mass spectrometry (MS) 730:751 This fact is probably due to the absence of an enzyme for general release of O-linked saccharides from glycoproteins and due to their low ionization yield in mass spectrometry (MS). 26184710 11 74 theme high 1734:1737 arg1 instrument 1759:1768 a high resolution Qq-oaTOF instrument 1732:1768 a high resolution Qq-oaTOF instrument 1732:1768 For the determination of O-glycan profiles in mixtures, a HPLC separation was combined with a high resolution Qq-oaTOF instrument. 26184710 7 75 theme improved 1032:1039 arg1 analysis 1054:1061 improved quantitative analysis 1032:1061 improved quantitative analysis 1032:1061 For the purpose of improved quantitative analysis, stable-isotope coded labeling by d0/d5 1-phenyl-3-methyl-5-pyrazolidone (PMP) was performed. 26184710 10 76 theme higher 1493:1498 arg1 O-glycans 1509:1517 higher abundant O-glycans 1493:1517 higher abundant O-glycans 1493:1517 For higher abundant O-glycans a mean coefficient of variation (CV) less than 6% could be attained, for very low abundant CV values between 15 and 20%. 26184710 0 77 theme deuterated 106:115 arg1 1-phenyl-3-methyl-5-pyrazolone 117:146 deuterated 1-phenyl-3-methyl-5-pyrazolone 106:146 deuterated 1-phenyl-3-methyl-5-pyrazolone 106:146 Quantitative fingerprinting of O-linked glycans released from proteins using isotopic coded labeling with deuterated 1-phenyl-3-methyl-5-pyrazolone. 26184710 9 78 theme yields 1368:1373 arg1 enhancement 1342:1352 an enhancement 1339:1352 an enhancement of ionization yields in MS. By introducing an internal standard (e.g. GlcNAc3) the reproducibility for quantification can be improved 1339:1486 Beneath improving the reproducibility of quantitation, PMP derivatization contributed to an enhancement of ionization yields in MS. By introducing an internal standard (e.g. GlcNAc3) the reproducibility for quantification can be improved. 26184710 4 79 gly glycoproteins 675:687 arg1 glycoproteins 675:687 glycoproteins 675:687 glycoproteins 675:687 This fact is probably due to the absence of an enzyme for general release of O-linked saccharides from glycoproteins and due to their low ionization yield in mass spectrometry (MS). 26184710 10 80 theme mean 1521:1524 arg1 coefficient 1526:1536 a mean coefficient 1519:1536 a mean coefficient of variation (CV) less than 6% 1519:1567 For higher abundant O-glycans a mean coefficient of variation (CV) less than 6% could be attained, for very low abundant CV values between 15 and 20%. 26184710 13 81 theme separation 1880:1889 arg1 step 1891:1894 This separation step 1875:1894 This separation step 1875:1894 This separation step was particularly useful for removing of salts avoiding so the presence of various sodium clusters in the MS spectrum. 26184710 2 82 theme recent 447:452 arg1 years 454:458 recent years 447:458 recent years 447:458 The development of new tools for qualitative and quantitative analysis of glycans has gained high importance in recent years. 26184710 0 83 theme O-linked 31:38 arg1 glycans 40:46 O-linked glycans 31:46 O-linked glycans 31:46 Quantitative fingerprinting of O-linked glycans released from proteins using isotopic coded labeling with deuterated 1-phenyl-3-methyl-5-pyrazolone. 26184710 4 84 theme enzyme 619:624 arg1 absence 605:611 the absence 601:611 the absence of an enzyme for general release of O-linked saccharides from glycoproteins 601:687 This fact is probably due to the absence of an enzyme for general release of O-linked saccharides from glycoproteins and due to their low ionization yield in mass spectrometry (MS). 26184710 5 85 theme improved 802:809 arg1 analysis 840:847 improved qualitative and quantitative analysis 802:847 improved qualitative and quantitative analysis of mucin-type O-glycans 802:871 In this paper, a method is established aimed at improved qualitative and quantitative analysis of mucin-type O-glycans. 26184710 8 86 theme heavy 1162:1166 arg1 -version 1168:1175 The "heavy"-version 1157:1175 The "heavy"-version 1157:1175 The "heavy"-version of this label, penta-deutero (d5)-PMP, was synthesized for this purpose. 26184710 3 87 theme quantitative 512:523 arg1 data 525:528 quantitative data 512:528 quantitative data 512:528 This is particularly true with O-glycans for which quantitative data are still underrepresented in literature. 26184710 4 88 link O-linked 649:656 arg1 saccharides 658:668 O-linked saccharides 649:668 O-linked saccharides 649:668 This fact is probably due to the absence of an enzyme for general release of O-linked saccharides from glycoproteins and due to their low ionization yield in mass spectrometry (MS). 26184710 12 89 theme separating 1816:1825 arg1 some 1852:1855 some 1852:1855 some 1852:1855 RP-type stationary phases were successful in separating glycan species including some of isomeric ones. 26184710 12 89 theme separating 1816:1825 arg1 ones 1869:1872 isomeric ones 1860:1872 isomeric ones 1860:1872 RP-type stationary phases were successful in separating glycan species including some of isomeric ones. 26184710 12 89 theme separating 1816:1825 arg1 species 1834:1840 separating glycan species 1816:1840 separating glycan species including some of isomeric ones 1816:1872 RP-type stationary phases were successful in separating glycan species including some of isomeric ones. 26184710 11 90 from determination 1648:1660 arg1 mixtures 1686:1693 mixtures 1686:1693 mixtures 1686:1693 For the determination of O-glycan profiles in mixtures, a HPLC separation was combined with a high resolution Qq-oaTOF instrument. 26184710 8 91 theme this 1180:1183 arg1 -version 1168:1175 The "heavy"-version 1157:1175 The "heavy"-version 1157:1175 The "heavy"-version of this label, penta-deutero (d5)-PMP, was synthesized for this purpose. 26184710 6 92 theme chemical 876:883 arg1 reaction 885:892 A chemical reaction 874:892 A chemical reaction combining release and derivatization of O-glycans in one step 874:954 A chemical reaction combining release and derivatization of O-glycans in one step is combined here with mass spectrometric quantification. 26184710 4 93 theme saccharides 658:668 arg1 release 638:644 general release 630:644 general release of O-linked saccharides from glycoproteins 630:687 This fact is probably due to the absence of an enzyme for general release of O-linked saccharides from glycoproteins and due to their low ionization yield in mass spectrometry (MS). 26184710 12 94 from successful 1802:1811 arg1 some 1852:1855 some 1852:1855 some 1852:1855 RP-type stationary phases were successful in separating glycan species including some of isomeric ones. 26184710 12 94 from successful 1802:1811 arg1 ones 1869:1872 isomeric ones 1860:1872 isomeric ones 1860:1872 RP-type stationary phases were successful in separating glycan species including some of isomeric ones. 26184710 12 94 from successful 1802:1811 arg1 species 1834:1840 separating glycan species 1816:1840 separating glycan species including some of isomeric ones 1816:1872 RP-type stationary phases were successful in separating glycan species including some of isomeric ones. 24810740 0 0 theme sludge 62:67 arg1 conditioning 69:80 sewage sludge conditioning 55:80 sewage sludge conditioning 55:80 Mechanism of red mud combined with Fenton's reagent in sewage sludge conditioning. 24810740 4 1 theme dissolved 824:832 arg1 organics 834:841 dissolved organics 824:841 dissolved organics 824:841 The mechanism of the composite conditioner could be illuminated as follows: (1) extracellular polymeric substances (EPS), including loosely bound EPS and tightly bound EPS, were degraded into dissolved organics, e.g., proteins and polysaccharides; (2) bound water was released and converted into free water due to the degradation of EPS; and (3) morphology of the conditioned sludge exhibited a porous structure in contrast with the compact structure of raw sludge, and the addition of red mud formed new mineral phases and a rigid lattice structure in sludge, allowing the outflow of free water. 24810740 4 2 theme polymeric 726:734 arg1 EPS 748:750 EPS 748:750 EPS 748:750 The mechanism of the composite conditioner could be illuminated as follows: (1) extracellular polymeric substances (EPS), including loosely bound EPS and tightly bound EPS, were degraded into dissolved organics, e.g., proteins and polysaccharides; (2) bound water was released and converted into free water due to the degradation of EPS; and (3) morphology of the conditioned sludge exhibited a porous structure in contrast with the compact structure of raw sludge, and the addition of red mud formed new mineral phases and a rigid lattice structure in sludge, allowing the outflow of free water. 24810740 4 2 theme polymeric 726:734 arg1 substances 736:745 (1) extracellular polymeric substances 708:745 (1) extracellular polymeric substances (EPS) 708:751 The mechanism of the composite conditioner could be illuminated as follows: (1) extracellular polymeric substances (EPS), including loosely bound EPS and tightly bound EPS, were degraded into dissolved organics, e.g., proteins and polysaccharides; (2) bound water was released and converted into free water due to the degradation of EPS; and (3) morphology of the conditioned sludge exhibited a porous structure in contrast with the compact structure of raw sludge, and the addition of red mud formed new mineral phases and a rigid lattice structure in sludge, allowing the outflow of free water. 24810740 2 3 theme filtrate 318:325 arg1 pH 308:309 the pH 304:309 the pH of the filtrate close to neutrality 304:345 The results show that red mud combined with Fenton's reagent showed good conditioning capability with the pH of the filtrate close to neutrality, indicating that red mud acted as a neutralizer as well as a skeleton builder when jointly used with Fenton's reagent. 24810740 0 4 theme sewage 55:60 arg1 conditioning 69:80 sewage sludge conditioning 55:80 sewage sludge conditioning 55:80 Mechanism of red mud combined with Fenton's reagent in sewage sludge conditioning. 24810740 4 5 theme mud 1122:1124 arg1 addition 1106:1113 the addition 1102:1113 the addition of red mud 1102:1124 The mechanism of the composite conditioner could be illuminated as follows: (1) extracellular polymeric substances (EPS), including loosely bound EPS and tightly bound EPS, were degraded into dissolved organics, e.g., proteins and polysaccharides; (2) bound water was released and converted into free water due to the degradation of EPS; and (3) morphology of the conditioned sludge exhibited a porous structure in contrast with the compact structure of raw sludge, and the addition of red mud formed new mineral phases and a rigid lattice structure in sludge, allowing the outflow of free water. 24810740 4 6 theme extracellular 712:724 arg1 EPS 748:750 EPS 748:750 EPS 748:750 The mechanism of the composite conditioner could be illuminated as follows: (1) extracellular polymeric substances (EPS), including loosely bound EPS and tightly bound EPS, were degraded into dissolved organics, e.g., proteins and polysaccharides; (2) bound water was released and converted into free water due to the degradation of EPS; and (3) morphology of the conditioned sludge exhibited a porous structure in contrast with the compact structure of raw sludge, and the addition of red mud formed new mineral phases and a rigid lattice structure in sludge, allowing the outflow of free water. 24810740 4 6 theme extracellular 712:724 arg1 substances 736:745 (1) extracellular polymeric substances 708:745 (1) extracellular polymeric substances (EPS) 708:751 The mechanism of the composite conditioner could be illuminated as follows: (1) extracellular polymeric substances (EPS), including loosely bound EPS and tightly bound EPS, were degraded into dissolved organics, e.g., proteins and polysaccharides; (2) bound water was released and converted into free water due to the degradation of EPS; and (3) morphology of the conditioned sludge exhibited a porous structure in contrast with the compact structure of raw sludge, and the addition of red mud formed new mineral phases and a rigid lattice structure in sludge, allowing the outflow of free water. 24810740 3 7 theme H2O2 541:544 arg1 dosages 522:528 the optimal dosages 510:528 the optimal dosages of Fe(2+), H2O2 and red mud 510:556 Through response surface methodology (RSM), the optimal dosages of Fe(2+), H2O2 and red mud were proposed as 31.9, 33.7 and 275.1 mg/g DS (dry solids), respectively. 24810740 3 7 theme H2O2 541:544 arg1 33.7 581:584 33.7 581:584 33.7 581:584 Through response surface methodology (RSM), the optimal dosages of Fe(2+), H2O2 and red mud were proposed as 31.9, 33.7 and 275.1 mg/g DS (dry solids), respectively. 24810740 3 7 theme H2O2 541:544 arg1 31.9 575:578 31.9 575:578 31.9 575:578 Through response surface methodology (RSM), the optimal dosages of Fe(2+), H2O2 and red mud were proposed as 31.9, 33.7 and 275.1 mg/g DS (dry solids), respectively. 24810740 3 7 theme H2O2 541:544 arg1 DS 601:602 275.1 mg/g DS 590:602 275.1 mg/g DS (dry solids) 590:615 Through response surface methodology (RSM), the optimal dosages of Fe(2+), H2O2 and red mud were proposed as 31.9, 33.7 and 275.1 mg/g DS (dry solids), respectively. 24810740 4 8 theme red 1118:1120 arg1 mud 1122:1124 red mud 1118:1124 red mud 1118:1124 The mechanism of the composite conditioner could be illuminated as follows: (1) extracellular polymeric substances (EPS), including loosely bound EPS and tightly bound EPS, were degraded into dissolved organics, e.g., proteins and polysaccharides; (2) bound water was released and converted into free water due to the degradation of EPS; and (3) morphology of the conditioned sludge exhibited a porous structure in contrast with the compact structure of raw sludge, and the addition of red mud formed new mineral phases and a rigid lattice structure in sludge, allowing the outflow of free water. 24810740 5 9 theme dewatering 1242:1251 arg1 performance 1253:1263 sludge dewatering performance 1235:1263 sludge dewatering performance 1235:1263 Thus, sludge dewatering performance was effectively improved. 24810740 3 10 theme surface 483:489 arg1 RSM 504:506 RSM 504:506 RSM 504:506 Through response surface methodology (RSM), the optimal dosages of Fe(2+), H2O2 and red mud were proposed as 31.9, 33.7 and 275.1 mg/g DS (dry solids), respectively. 24810740 3 10 theme surface 483:489 arg1 methodology 491:501 response surface methodology 474:501 response surface methodology (RSM) 474:507 Through response surface methodology (RSM), the optimal dosages of Fe(2+), H2O2 and red mud were proposed as 31.9, 33.7 and 275.1 mg/g DS (dry solids), respectively. 24810740 4 11 theme conditioned 996:1006 arg1 sludge 1008:1013 the conditioned sludge 992:1013 the conditioned sludge 992:1013 The mechanism of the composite conditioner could be illuminated as follows: (1) extracellular polymeric substances (EPS), including loosely bound EPS and tightly bound EPS, were degraded into dissolved organics, e.g., proteins and polysaccharides; (2) bound water was released and converted into free water due to the degradation of EPS; and (3) morphology of the conditioned sludge exhibited a porous structure in contrast with the compact structure of raw sludge, and the addition of red mud formed new mineral phases and a rigid lattice structure in sludge, allowing the outflow of free water. 24810740 6 12 theme DS 1519:1520 arg1 saving 1467:1472 a saving 1465:1472 a saving of approximately 411,000 USD/y or 50.8 USD/t DS comparing with using lime and ordinary Portland cement combined with Fenton's reagent, and approximately 612,000 USD/y or 75.5 USD/t DS comparing with the traditional treatment 1465:1697 The economic assessment for a wastewater treatment plant of 370,000 equivalent inhabitants confirms that using red mud conditioning, combined with Fenton's reagent, leads to a saving of approximately 411,000 USD/y or 50.8 USD/t DS comparing with using lime and ordinary Portland cement combined with Fenton's reagent, and approximately 612,000 USD/y or 75.5 USD/t DS comparing with the traditional treatment. 24810740 3 13 theme dry 605:607 arg1 DS 601:602 275.1 mg/g DS 590:602 275.1 mg/g DS (dry solids) 590:615 Through response surface methodology (RSM), the optimal dosages of Fe(2+), H2O2 and red mud were proposed as 31.9, 33.7 and 275.1 mg/g DS (dry solids), respectively. 24810740 3 13 theme dry 605:607 arg1 solids 609:614 dry solids 605:614 dry solids 605:614 Through response surface methodology (RSM), the optimal dosages of Fe(2+), H2O2 and red mud were proposed as 31.9, 33.7 and 275.1 mg/g DS (dry solids), respectively. 24810740 4 14 theme free 1217:1220 arg1 water 1222:1226 free water 1217:1226 free water 1217:1226 The mechanism of the composite conditioner could be illuminated as follows: (1) extracellular polymeric substances (EPS), including loosely bound EPS and tightly bound EPS, were degraded into dissolved organics, e.g., proteins and polysaccharides; (2) bound water was released and converted into free water due to the degradation of EPS; and (3) morphology of the conditioned sludge exhibited a porous structure in contrast with the compact structure of raw sludge, and the addition of red mud formed new mineral phases and a rigid lattice structure in sludge, allowing the outflow of free water. 24810740 3 15 theme 275.1 mg/g 590:599 arg1 dosages 522:528 the optimal dosages 510:528 the optimal dosages of Fe(2+), H2O2 and red mud 510:556 Through response surface methodology (RSM), the optimal dosages of Fe(2+), H2O2 and red mud were proposed as 31.9, 33.7 and 275.1 mg/g DS (dry solids), respectively. 24810740 3 15 theme 275.1 mg/g 590:599 arg1 DS 601:602 275.1 mg/g DS 590:602 275.1 mg/g DS (dry solids) 590:615 Through response surface methodology (RSM), the optimal dosages of Fe(2+), H2O2 and red mud were proposed as 31.9, 33.7 and 275.1 mg/g DS (dry solids), respectively. 24810740 3 15 theme 275.1 mg/g 590:599 arg1 solids 609:614 dry solids 605:614 dry solids 605:614 Through response surface methodology (RSM), the optimal dosages of Fe(2+), H2O2 and red mud were proposed as 31.9, 33.7 and 275.1 mg/g DS (dry solids), respectively. 24810740 6 16 theme red 1402:1404 arg1 conditioning 1410:1421 red mud conditioning 1402:1421 red mud conditioning 1402:1421 The economic assessment for a wastewater treatment plant of 370,000 equivalent inhabitants confirms that using red mud conditioning, combined with Fenton's reagent, leads to a saving of approximately 411,000 USD/y or 50.8 USD/t DS comparing with using lime and ordinary Portland cement combined with Fenton's reagent, and approximately 612,000 USD/y or 75.5 USD/t DS comparing with the traditional treatment. 24810740 3 17 theme response 474:481 arg1 RSM 504:506 RSM 504:506 RSM 504:506 Through response surface methodology (RSM), the optimal dosages of Fe(2+), H2O2 and red mud were proposed as 31.9, 33.7 and 275.1 mg/g DS (dry solids), respectively. 24810740 3 17 theme response 474:481 arg1 methodology 491:501 response surface methodology 474:501 response surface methodology (RSM) 474:507 Through response surface methodology (RSM), the optimal dosages of Fe(2+), H2O2 and red mud were proposed as 31.9, 33.7 and 275.1 mg/g DS (dry solids), respectively. 24810740 6 18 theme 50.8 1508:1511 arg1 USD/t 1513:1517 USD/t 1513:1517 USD/t 1513:1517 The economic assessment for a wastewater treatment plant of 370,000 equivalent inhabitants confirms that using red mud conditioning, combined with Fenton's reagent, leads to a saving of approximately 411,000 USD/y or 50.8 USD/t DS comparing with using lime and ordinary Portland cement combined with Fenton's reagent, and approximately 612,000 USD/y or 75.5 USD/t DS comparing with the traditional treatment. 24810740 6 19 theme treatment 1332:1340 arg1 plant 1342:1346 a wastewater treatment plant 1319:1346 a wastewater treatment plant 1319:1346 The economic assessment for a wastewater treatment plant of 370,000 equivalent inhabitants confirms that using red mud conditioning, combined with Fenton's reagent, leads to a saving of approximately 411,000 USD/y or 50.8 USD/t DS comparing with using lime and ordinary Portland cement combined with Fenton's reagent, and approximately 612,000 USD/y or 75.5 USD/t DS comparing with the traditional treatment. 24810740 4 20 dep released 900:907 arg1 bound 884:888 bound 884:888 bound 884:888 The mechanism of the composite conditioner could be illuminated as follows: (1) extracellular polymeric substances (EPS), including loosely bound EPS and tightly bound EPS, were degraded into dissolved organics, e.g., proteins and polysaccharides; (2) bound water was released and converted into free water due to the degradation of EPS; and (3) morphology of the conditioned sludge exhibited a porous structure in contrast with the compact structure of raw sludge, and the addition of red mud formed new mineral phases and a rigid lattice structure in sludge, allowing the outflow of free water. 24810740 4 20 dep released 900:907 arg1 2 881:881 2 881:881 2 881:881 The mechanism of the composite conditioner could be illuminated as follows: (1) extracellular polymeric substances (EPS), including loosely bound EPS and tightly bound EPS, were degraded into dissolved organics, e.g., proteins and polysaccharides; (2) bound water was released and converted into free water due to the degradation of EPS; and (3) morphology of the conditioned sludge exhibited a porous structure in contrast with the compact structure of raw sludge, and the addition of red mud formed new mineral phases and a rigid lattice structure in sludge, allowing the outflow of free water. 24810740 4 21 theme sludge 1090:1095 arg1 structure 1073:1081 the compact structure 1061:1081 the compact structure of raw sludge 1061:1095 The mechanism of the composite conditioner could be illuminated as follows: (1) extracellular polymeric substances (EPS), including loosely bound EPS and tightly bound EPS, were degraded into dissolved organics, e.g., proteins and polysaccharides; (2) bound water was released and converted into free water due to the degradation of EPS; and (3) morphology of the conditioned sludge exhibited a porous structure in contrast with the compact structure of raw sludge, and the addition of red mud formed new mineral phases and a rigid lattice structure in sludge, allowing the outflow of free water. 24810740 6 22 theme USD/t 1649:1653 arg1 reagent 1600:1606 Fenton's reagent 1591:1606 Fenton's reagent 1591:1606 The economic assessment for a wastewater treatment plant of 370,000 equivalent inhabitants confirms that using red mud conditioning, combined with Fenton's reagent, leads to a saving of approximately 411,000 USD/y or 50.8 USD/t DS comparing with using lime and ordinary Portland cement combined with Fenton's reagent, and approximately 612,000 USD/y or 75.5 USD/t DS comparing with the traditional treatment. 24810740 6 22 theme USD/t 1649:1653 arg1 DS 1655:1656 75.5 USD/t DS 1644:1656 75.5 USD/t DS 1644:1656 The economic assessment for a wastewater treatment plant of 370,000 equivalent inhabitants confirms that using red mud conditioning, combined with Fenton's reagent, leads to a saving of approximately 411,000 USD/y or 50.8 USD/t DS comparing with using lime and ordinary Portland cement combined with Fenton's reagent, and approximately 612,000 USD/y or 75.5 USD/t DS comparing with the traditional treatment. 24810740 6 23 theme Portland 1561:1568 arg1 cement 1570:1575 ordinary Portland cement 1552:1575 ordinary Portland cement 1552:1575 The economic assessment for a wastewater treatment plant of 370,000 equivalent inhabitants confirms that using red mud conditioning, combined with Fenton's reagent, leads to a saving of approximately 411,000 USD/y or 50.8 USD/t DS comparing with using lime and ordinary Portland cement combined with Fenton's reagent, and approximately 612,000 USD/y or 75.5 USD/t DS comparing with the traditional treatment. 24810740 4 24 dep proteins 850:857 arg1 e.g. 844:847 e.g. 844:847 e.g. 844:847 The mechanism of the composite conditioner could be illuminated as follows: (1) extracellular polymeric substances (EPS), including loosely bound EPS and tightly bound EPS, were degraded into dissolved organics, e.g., proteins and polysaccharides; (2) bound water was released and converted into free water due to the degradation of EPS; and (3) morphology of the conditioned sludge exhibited a porous structure in contrast with the compact structure of raw sludge, and the addition of red mud formed new mineral phases and a rigid lattice structure in sludge, allowing the outflow of free water. 24810740 4 25 theme sludge 1008:1013 arg1 morphology 978:987 (3) morphology 974:987 (3) morphology of the conditioned sludge 974:1013 The mechanism of the composite conditioner could be illuminated as follows: (1) extracellular polymeric substances (EPS), including loosely bound EPS and tightly bound EPS, were degraded into dissolved organics, e.g., proteins and polysaccharides; (2) bound water was released and converted into free water due to the degradation of EPS; and (3) morphology of the conditioned sludge exhibited a porous structure in contrast with the compact structure of raw sludge, and the addition of red mud formed new mineral phases and a rigid lattice structure in sludge, allowing the outflow of free water. 24810740 2 26 theme conditioning 275:286 arg1 capability 288:297 good conditioning capability 270:297 good conditioning capability 270:297 The results show that red mud combined with Fenton's reagent showed good conditioning capability with the pH of the filtrate close to neutrality, indicating that red mud acted as a neutralizer as well as a skeleton builder when jointly used with Fenton's reagent. 24810740 4 27 dep morphology 978:987 arg1 3 975:975 3 975:975 3 975:975 The mechanism of the composite conditioner could be illuminated as follows: (1) extracellular polymeric substances (EPS), including loosely bound EPS and tightly bound EPS, were degraded into dissolved organics, e.g., proteins and polysaccharides; (2) bound water was released and converted into free water due to the degradation of EPS; and (3) morphology of the conditioned sludge exhibited a porous structure in contrast with the compact structure of raw sludge, and the addition of red mud formed new mineral phases and a rigid lattice structure in sludge, allowing the outflow of free water. 24810740 4 28 theme compact 1065:1071 arg1 structure 1073:1081 the compact structure 1061:1081 the compact structure of raw sludge 1061:1095 The mechanism of the composite conditioner could be illuminated as follows: (1) extracellular polymeric substances (EPS), including loosely bound EPS and tightly bound EPS, were degraded into dissolved organics, e.g., proteins and polysaccharides; (2) bound water was released and converted into free water due to the degradation of EPS; and (3) morphology of the conditioned sludge exhibited a porous structure in contrast with the compact structure of raw sludge, and the addition of red mud formed new mineral phases and a rigid lattice structure in sludge, allowing the outflow of free water. 24810740 0 29 theme mud 17:19 arg1 Mechanism 0:8 Mechanism 0:8 Mechanism of red mud 0:19 Mechanism of red mud combined with Fenton's reagent in sewage sludge conditioning. 24810740 3 30 theme Fe 533:534 arg1 dosages 522:528 the optimal dosages 510:528 the optimal dosages of Fe(2+), H2O2 and red mud 510:556 Through response surface methodology (RSM), the optimal dosages of Fe(2+), H2O2 and red mud were proposed as 31.9, 33.7 and 275.1 mg/g DS (dry solids), respectively. 24810740 3 30 theme Fe 533:534 arg1 33.7 581:584 33.7 581:584 33.7 581:584 Through response surface methodology (RSM), the optimal dosages of Fe(2+), H2O2 and red mud were proposed as 31.9, 33.7 and 275.1 mg/g DS (dry solids), respectively. 24810740 3 30 theme Fe 533:534 arg1 31.9 575:578 31.9 575:578 31.9 575:578 Through response surface methodology (RSM), the optimal dosages of Fe(2+), H2O2 and red mud were proposed as 31.9, 33.7 and 275.1 mg/g DS (dry solids), respectively. 24810740 3 30 theme Fe 533:534 arg1 DS 601:602 275.1 mg/g DS 590:602 275.1 mg/g DS (dry solids) 590:615 Through response surface methodology (RSM), the optimal dosages of Fe(2+), H2O2 and red mud were proposed as 31.9, 33.7 and 275.1 mg/g DS (dry solids), respectively. 24810740 4 31 theme bound 772:776 arg1 EPS 778:780 loosely bound EPS 764:780 loosely bound EPS 764:780 The mechanism of the composite conditioner could be illuminated as follows: (1) extracellular polymeric substances (EPS), including loosely bound EPS and tightly bound EPS, were degraded into dissolved organics, e.g., proteins and polysaccharides; (2) bound water was released and converted into free water due to the degradation of EPS; and (3) morphology of the conditioned sludge exhibited a porous structure in contrast with the compact structure of raw sludge, and the addition of red mud formed new mineral phases and a rigid lattice structure in sludge, allowing the outflow of free water. 24810740 4 32 theme porous 1027:1032 arg1 structure 1034:1042 a porous structure 1025:1042 a porous structure in contrast 1025:1054 The mechanism of the composite conditioner could be illuminated as follows: (1) extracellular polymeric substances (EPS), including loosely bound EPS and tightly bound EPS, were degraded into dissolved organics, e.g., proteins and polysaccharides; (2) bound water was released and converted into free water due to the degradation of EPS; and (3) morphology of the conditioned sludge exhibited a porous structure in contrast with the compact structure of raw sludge, and the addition of red mud formed new mineral phases and a rigid lattice structure in sludge, allowing the outflow of free water. 24810740 2 33 theme good 270:273 arg1 capability 288:297 good conditioning capability 270:297 good conditioning capability 270:297 The results show that red mud combined with Fenton's reagent showed good conditioning capability with the pH of the filtrate close to neutrality, indicating that red mud acted as a neutralizer as well as a skeleton builder when jointly used with Fenton's reagent. 24810740 4 34 theme water 1222:1226 arg1 outflow 1206:1212 the outflow 1202:1212 the outflow of free water 1202:1226 The mechanism of the composite conditioner could be illuminated as follows: (1) extracellular polymeric substances (EPS), including loosely bound EPS and tightly bound EPS, were degraded into dissolved organics, e.g., proteins and polysaccharides; (2) bound water was released and converted into free water due to the degradation of EPS; and (3) morphology of the conditioned sludge exhibited a porous structure in contrast with the compact structure of raw sludge, and the addition of red mud formed new mineral phases and a rigid lattice structure in sludge, allowing the outflow of free water. 24810740 0 35 theme red 13:15 arg1 mud 17:19 red mud 13:19 red mud 13:19 Mechanism of red mud combined with Fenton's reagent in sewage sludge conditioning. 24810740 4 36 theme lattice 1164:1170 arg1 structure 1172:1180 a rigid lattice structure 1156:1180 a rigid lattice structure 1156:1180 The mechanism of the composite conditioner could be illuminated as follows: (1) extracellular polymeric substances (EPS), including loosely bound EPS and tightly bound EPS, were degraded into dissolved organics, e.g., proteins and polysaccharides; (2) bound water was released and converted into free water due to the degradation of EPS; and (3) morphology of the conditioned sludge exhibited a porous structure in contrast with the compact structure of raw sludge, and the addition of red mud formed new mineral phases and a rigid lattice structure in sludge, allowing the outflow of free water. 24810740 4 37 dep follows 699:705 arg1 degraded 810:817 degraded 810:817 degraded 810:817 The mechanism of the composite conditioner could be illuminated as follows: (1) extracellular polymeric substances (EPS), including loosely bound EPS and tightly bound EPS, were degraded into dissolved organics, e.g., proteins and polysaccharides; (2) bound water was released and converted into free water due to the degradation of EPS; and (3) morphology of the conditioned sludge exhibited a porous structure in contrast with the compact structure of raw sludge, and the addition of red mud formed new mineral phases and a rigid lattice structure in sludge, allowing the outflow of free water. 24810740 4 37 dep follows 699:705 arg1 EPS 748:750 EPS 748:750 EPS 748:750 The mechanism of the composite conditioner could be illuminated as follows: (1) extracellular polymeric substances (EPS), including loosely bound EPS and tightly bound EPS, were degraded into dissolved organics, e.g., proteins and polysaccharides; (2) bound water was released and converted into free water due to the degradation of EPS; and (3) morphology of the conditioned sludge exhibited a porous structure in contrast with the compact structure of raw sludge, and the addition of red mud formed new mineral phases and a rigid lattice structure in sludge, allowing the outflow of free water. 24810740 4 37 dep follows 699:705 arg1 tightly 786:792 tightly 786:792 tightly 786:792 The mechanism of the composite conditioner could be illuminated as follows: (1) extracellular polymeric substances (EPS), including loosely bound EPS and tightly bound EPS, were degraded into dissolved organics, e.g., proteins and polysaccharides; (2) bound water was released and converted into free water due to the degradation of EPS; and (3) morphology of the conditioned sludge exhibited a porous structure in contrast with the compact structure of raw sludge, and the addition of red mud formed new mineral phases and a rigid lattice structure in sludge, allowing the outflow of free water. 24810740 4 37 dep follows 699:705 arg1 including 754:762 including 754:762 including loosely bound EPS 754:780 The mechanism of the composite conditioner could be illuminated as follows: (1) extracellular polymeric substances (EPS), including loosely bound EPS and tightly bound EPS, were degraded into dissolved organics, e.g., proteins and polysaccharides; (2) bound water was released and converted into free water due to the degradation of EPS; and (3) morphology of the conditioned sludge exhibited a porous structure in contrast with the compact structure of raw sludge, and the addition of red mud formed new mineral phases and a rigid lattice structure in sludge, allowing the outflow of free water. 24810740 4 37 dep follows 699:705 arg1 bound 794:798 bound 794:798 bound EPS 794:802 The mechanism of the composite conditioner could be illuminated as follows: (1) extracellular polymeric substances (EPS), including loosely bound EPS and tightly bound EPS, were degraded into dissolved organics, e.g., proteins and polysaccharides; (2) bound water was released and converted into free water due to the degradation of EPS; and (3) morphology of the conditioned sludge exhibited a porous structure in contrast with the compact structure of raw sludge, and the addition of red mud formed new mineral phases and a rigid lattice structure in sludge, allowing the outflow of free water. 24810740 4 37 dep follows 699:705 arg1 substances 736:745 (1) extracellular polymeric substances 708:745 (1) extracellular polymeric substances (EPS) 708:751 The mechanism of the composite conditioner could be illuminated as follows: (1) extracellular polymeric substances (EPS), including loosely bound EPS and tightly bound EPS, were degraded into dissolved organics, e.g., proteins and polysaccharides; (2) bound water was released and converted into free water due to the degradation of EPS; and (3) morphology of the conditioned sludge exhibited a porous structure in contrast with the compact structure of raw sludge, and the addition of red mud formed new mineral phases and a rigid lattice structure in sludge, allowing the outflow of free water. 24810740 1 38 theme sewage 174:179 arg1 conditioning 188:199 sewage sludge conditioning 174:199 sewage sludge conditioning 174:199 Red mud was evaluated as an alternative skeleton builder combined with Fenton's reagent in sewage sludge conditioning. 24810740 4 39 theme rigid 1158:1162 arg1 structure 1172:1180 a rigid lattice structure 1156:1180 a rigid lattice structure 1156:1180 The mechanism of the composite conditioner could be illuminated as follows: (1) extracellular polymeric substances (EPS), including loosely bound EPS and tightly bound EPS, were degraded into dissolved organics, e.g., proteins and polysaccharides; (2) bound water was released and converted into free water due to the degradation of EPS; and (3) morphology of the conditioned sludge exhibited a porous structure in contrast with the compact structure of raw sludge, and the addition of red mud formed new mineral phases and a rigid lattice structure in sludge, allowing the outflow of free water. 24810740 3 40 theme red 550:552 arg1 mud 554:556 red mud 550:556 red mud 550:556 Through response surface methodology (RSM), the optimal dosages of Fe(2+), H2O2 and red mud were proposed as 31.9, 33.7 and 275.1 mg/g DS (dry solids), respectively. 24810740 4 41 theme free 928:931 arg1 water 933:937 free water 928:937 free water 928:937 The mechanism of the composite conditioner could be illuminated as follows: (1) extracellular polymeric substances (EPS), including loosely bound EPS and tightly bound EPS, were degraded into dissolved organics, e.g., proteins and polysaccharides; (2) bound water was released and converted into free water due to the degradation of EPS; and (3) morphology of the conditioned sludge exhibited a porous structure in contrast with the compact structure of raw sludge, and the addition of red mud formed new mineral phases and a rigid lattice structure in sludge, allowing the outflow of free water. 24810740 1 42 theme sludge 181:186 arg1 conditioning 188:199 sewage sludge conditioning 174:199 sewage sludge conditioning 174:199 Red mud was evaluated as an alternative skeleton builder combined with Fenton's reagent in sewage sludge conditioning. 24810740 2 43 theme skeleton 408:415 arg1 mud 368:370 red mud 364:370 red mud 364:370 The results show that red mud combined with Fenton's reagent showed good conditioning capability with the pH of the filtrate close to neutrality, indicating that red mud acted as a neutralizer as well as a skeleton builder when jointly used with Fenton's reagent. 24810740 2 43 theme skeleton 408:415 arg1 builder 417:423 a skeleton builder 406:423 a neutralizer as well as a skeleton builder 381:423 The results show that red mud combined with Fenton's reagent showed good conditioning capability with the pH of the filtrate close to neutrality, indicating that red mud acted as a neutralizer as well as a skeleton builder when jointly used with Fenton's reagent. 24810740 4 44 theme new 1133:1135 arg1 phases 1145:1150 new mineral phases 1133:1150 new mineral phases 1133:1150 The mechanism of the composite conditioner could be illuminated as follows: (1) extracellular polymeric substances (EPS), including loosely bound EPS and tightly bound EPS, were degraded into dissolved organics, e.g., proteins and polysaccharides; (2) bound water was released and converted into free water due to the degradation of EPS; and (3) morphology of the conditioned sludge exhibited a porous structure in contrast with the compact structure of raw sludge, and the addition of red mud formed new mineral phases and a rigid lattice structure in sludge, allowing the outflow of free water. 24810740 4 45 dep substances 736:745 arg1 1 709:709 1 709:709 1 709:709 The mechanism of the composite conditioner could be illuminated as follows: (1) extracellular polymeric substances (EPS), including loosely bound EPS and tightly bound EPS, were degraded into dissolved organics, e.g., proteins and polysaccharides; (2) bound water was released and converted into free water due to the degradation of EPS; and (3) morphology of the conditioned sludge exhibited a porous structure in contrast with the compact structure of raw sludge, and the addition of red mud formed new mineral phases and a rigid lattice structure in sludge, allowing the outflow of free water. 24810740 4 46 theme raw 1086:1088 arg1 sludge 1090:1095 raw sludge 1086:1095 raw sludge 1086:1095 The mechanism of the composite conditioner could be illuminated as follows: (1) extracellular polymeric substances (EPS), including loosely bound EPS and tightly bound EPS, were degraded into dissolved organics, e.g., proteins and polysaccharides; (2) bound water was released and converted into free water due to the degradation of EPS; and (3) morphology of the conditioned sludge exhibited a porous structure in contrast with the compact structure of raw sludge, and the addition of red mud formed new mineral phases and a rigid lattice structure in sludge, allowing the outflow of free water. 24810740 6 47 theme 75.5 1644:1647 arg1 USD/t 1649:1653 USD/t 1649:1653 USD/t 1649:1653 The economic assessment for a wastewater treatment plant of 370,000 equivalent inhabitants confirms that using red mud conditioning, combined with Fenton's reagent, leads to a saving of approximately 411,000 USD/y or 50.8 USD/t DS comparing with using lime and ordinary Portland cement combined with Fenton's reagent, and approximately 612,000 USD/y or 75.5 USD/t DS comparing with the traditional treatment. 24810740 6 48 theme inhabitants 1370:1380 arg1 assessment 1304:1313 The economic assessment 1291:1313 The economic assessment for a wastewater treatment plant of 370,000 equivalent inhabitants 1291:1380 The economic assessment for a wastewater treatment plant of 370,000 equivalent inhabitants confirms that using red mud conditioning, combined with Fenton's reagent, leads to a saving of approximately 411,000 USD/y or 50.8 USD/t DS comparing with using lime and ordinary Portland cement combined with Fenton's reagent, and approximately 612,000 USD/y or 75.5 USD/t DS comparing with the traditional treatment. 24810740 2 49 theme red 364:366 arg1 mud 368:370 red mud 364:370 red mud 364:370 The results show that red mud combined with Fenton's reagent showed good conditioning capability with the pH of the filtrate close to neutrality, indicating that red mud acted as a neutralizer as well as a skeleton builder when jointly used with Fenton's reagent. 24810740 2 49 theme red 364:366 arg1 neutralizer 383:393 a neutralizer 381:393 a neutralizer as well as a skeleton builder 381:423 The results show that red mud combined with Fenton's reagent showed good conditioning capability with the pH of the filtrate close to neutrality, indicating that red mud acted as a neutralizer as well as a skeleton builder when jointly used with Fenton's reagent. 24810740 2 49 theme red 364:366 arg1 builder 417:423 a skeleton builder 406:423 a neutralizer as well as a skeleton builder 381:423 The results show that red mud combined with Fenton's reagent showed good conditioning capability with the pH of the filtrate close to neutrality, indicating that red mud acted as a neutralizer as well as a skeleton builder when jointly used with Fenton's reagent. 24810740 6 50 theme mud 1406:1408 arg1 conditioning 1410:1421 red mud conditioning 1402:1421 red mud conditioning 1402:1421 The economic assessment for a wastewater treatment plant of 370,000 equivalent inhabitants confirms that using red mud conditioning, combined with Fenton's reagent, leads to a saving of approximately 411,000 USD/y or 50.8 USD/t DS comparing with using lime and ordinary Portland cement combined with Fenton's reagent, and approximately 612,000 USD/y or 75.5 USD/t DS comparing with the traditional treatment. 24810740 0 51 from reagent 44:50 arg1 conditioning 69:80 sewage sludge conditioning 55:80 sewage sludge conditioning 55:80 Mechanism of red mud combined with Fenton's reagent in sewage sludge conditioning. 24810740 6 52 theme equivalent 1359:1368 arg1 inhabitants 1370:1380 370,000 equivalent inhabitants 1351:1380 370,000 equivalent inhabitants 1351:1380 The economic assessment for a wastewater treatment plant of 370,000 equivalent inhabitants confirms that using red mud conditioning, combined with Fenton's reagent, leads to a saving of approximately 411,000 USD/y or 50.8 USD/t DS comparing with using lime and ordinary Portland cement combined with Fenton's reagent, and approximately 612,000 USD/y or 75.5 USD/t DS comparing with the traditional treatment. 24810740 6 53 theme USD/y 1499:1503 arg1 saving 1467:1472 a saving 1465:1472 a saving of approximately 411,000 USD/y or 50.8 USD/t DS comparing with using lime and ordinary Portland cement combined with Fenton's reagent, and approximately 612,000 USD/y or 75.5 USD/t DS comparing with the traditional treatment 1465:1697 The economic assessment for a wastewater treatment plant of 370,000 equivalent inhabitants confirms that using red mud conditioning, combined with Fenton's reagent, leads to a saving of approximately 411,000 USD/y or 50.8 USD/t DS comparing with using lime and ordinary Portland cement combined with Fenton's reagent, and approximately 612,000 USD/y or 75.5 USD/t DS comparing with the traditional treatment. 24810740 3 54 theme optimal 514:520 arg1 dosages 522:528 the optimal dosages 510:528 the optimal dosages of Fe(2+), H2O2 and red mud 510:556 Through response surface methodology (RSM), the optimal dosages of Fe(2+), H2O2 and red mud were proposed as 31.9, 33.7 and 275.1 mg/g DS (dry solids), respectively. 24810740 3 54 theme optimal 514:520 arg1 33.7 581:584 33.7 581:584 33.7 581:584 Through response surface methodology (RSM), the optimal dosages of Fe(2+), H2O2 and red mud were proposed as 31.9, 33.7 and 275.1 mg/g DS (dry solids), respectively. 24810740 3 54 theme optimal 514:520 arg1 31.9 575:578 31.9 575:578 31.9 575:578 Through response surface methodology (RSM), the optimal dosages of Fe(2+), H2O2 and red mud were proposed as 31.9, 33.7 and 275.1 mg/g DS (dry solids), respectively. 24810740 3 54 theme optimal 514:520 arg1 DS 601:602 275.1 mg/g DS 590:602 275.1 mg/g DS (dry solids) 590:615 Through response surface methodology (RSM), the optimal dosages of Fe(2+), H2O2 and red mud were proposed as 31.9, 33.7 and 275.1 mg/g DS (dry solids), respectively. 24810740 5 55 theme sludge 1235:1240 arg1 performance 1253:1263 sludge dewatering performance 1235:1263 sludge dewatering performance 1235:1263 Thus, sludge dewatering performance was effectively improved. 24810740 4 56 theme mineral 1137:1143 arg1 phases 1145:1150 new mineral phases 1133:1150 new mineral phases 1133:1150 The mechanism of the composite conditioner could be illuminated as follows: (1) extracellular polymeric substances (EPS), including loosely bound EPS and tightly bound EPS, were degraded into dissolved organics, e.g., proteins and polysaccharides; (2) bound water was released and converted into free water due to the degradation of EPS; and (3) morphology of the conditioned sludge exhibited a porous structure in contrast with the compact structure of raw sludge, and the addition of red mud formed new mineral phases and a rigid lattice structure in sludge, allowing the outflow of free water. 24810740 4 57 theme composite 653:661 arg1 conditioner 663:673 the composite conditioner 649:673 the composite conditioner 649:673 The mechanism of the composite conditioner could be illuminated as follows: (1) extracellular polymeric substances (EPS), including loosely bound EPS and tightly bound EPS, were degraded into dissolved organics, e.g., proteins and polysaccharides; (2) bound water was released and converted into free water due to the degradation of EPS; and (3) morphology of the conditioned sludge exhibited a porous structure in contrast with the compact structure of raw sludge, and the addition of red mud formed new mineral phases and a rigid lattice structure in sludge, allowing the outflow of free water. 24810740 1 58 theme Red 83:85 arg1 builder 132:138 an alternative skeleton builder 108:138 an alternative skeleton builder combined with Fenton's reagent in sewage sludge conditioning 108:199 Red mud was evaluated as an alternative skeleton builder combined with Fenton's reagent in sewage sludge conditioning. 24810740 1 58 theme Red 83:85 arg1 mud 87:89 Red mud 83:89 Red mud 83:89 Red mud was evaluated as an alternative skeleton builder combined with Fenton's reagent in sewage sludge conditioning. 24810740 3 59 theme mud 554:556 arg1 dosages 522:528 the optimal dosages 510:528 the optimal dosages of Fe(2+), H2O2 and red mud 510:556 Through response surface methodology (RSM), the optimal dosages of Fe(2+), H2O2 and red mud were proposed as 31.9, 33.7 and 275.1 mg/g DS (dry solids), respectively. 24810740 3 59 theme mud 554:556 arg1 33.7 581:584 33.7 581:584 33.7 581:584 Through response surface methodology (RSM), the optimal dosages of Fe(2+), H2O2 and red mud were proposed as 31.9, 33.7 and 275.1 mg/g DS (dry solids), respectively. 24810740 3 59 theme mud 554:556 arg1 31.9 575:578 31.9 575:578 31.9 575:578 Through response surface methodology (RSM), the optimal dosages of Fe(2+), H2O2 and red mud were proposed as 31.9, 33.7 and 275.1 mg/g DS (dry solids), respectively. 24810740 3 59 theme mud 554:556 arg1 DS 601:602 275.1 mg/g DS 590:602 275.1 mg/g DS (dry solids) 590:615 Through response surface methodology (RSM), the optimal dosages of Fe(2+), H2O2 and red mud were proposed as 31.9, 33.7 and 275.1 mg/g DS (dry solids), respectively. 24810740 4 60 from structure 1034:1042 arg1 contrast 1047:1054 contrast 1047:1054 contrast 1047:1054 The mechanism of the composite conditioner could be illuminated as follows: (1) extracellular polymeric substances (EPS), including loosely bound EPS and tightly bound EPS, were degraded into dissolved organics, e.g., proteins and polysaccharides; (2) bound water was released and converted into free water due to the degradation of EPS; and (3) morphology of the conditioned sludge exhibited a porous structure in contrast with the compact structure of raw sludge, and the addition of red mud formed new mineral phases and a rigid lattice structure in sludge, allowing the outflow of free water. 24810740 4 61 theme EPS 965:967 arg1 degradation 950:960 the degradation 946:960 the degradation of EPS 946:967 The mechanism of the composite conditioner could be illuminated as follows: (1) extracellular polymeric substances (EPS), including loosely bound EPS and tightly bound EPS, were degraded into dissolved organics, e.g., proteins and polysaccharides; (2) bound water was released and converted into free water due to the degradation of EPS; and (3) morphology of the conditioned sludge exhibited a porous structure in contrast with the compact structure of raw sludge, and the addition of red mud formed new mineral phases and a rigid lattice structure in sludge, allowing the outflow of free water. 24810740 6 62 theme traditional 1677:1687 arg1 treatment 1689:1697 the traditional treatment 1673:1697 the traditional treatment 1673:1697 The economic assessment for a wastewater treatment plant of 370,000 equivalent inhabitants confirms that using red mud conditioning, combined with Fenton's reagent, leads to a saving of approximately 411,000 USD/y or 50.8 USD/t DS comparing with using lime and ordinary Portland cement combined with Fenton's reagent, and approximately 612,000 USD/y or 75.5 USD/t DS comparing with the traditional treatment. 24810740 6 63 theme economic 1295:1302 arg1 assessment 1304:1313 The economic assessment 1291:1313 The economic assessment for a wastewater treatment plant of 370,000 equivalent inhabitants 1291:1380 The economic assessment for a wastewater treatment plant of 370,000 equivalent inhabitants confirms that using red mud conditioning, combined with Fenton's reagent, leads to a saving of approximately 411,000 USD/y or 50.8 USD/t DS comparing with using lime and ordinary Portland cement combined with Fenton's reagent, and approximately 612,000 USD/y or 75.5 USD/t DS comparing with the traditional treatment. 24810740 2 64 theme red 224:226 arg1 mud 228:230 red mud 224:230 red mud combined with Fenton's reagent 224:261 The results show that red mud combined with Fenton's reagent showed good conditioning capability with the pH of the filtrate close to neutrality, indicating that red mud acted as a neutralizer as well as a skeleton builder when jointly used with Fenton's reagent. 24810740 1 65 from reagent 163:169 arg1 conditioning 188:199 sewage sludge conditioning 174:199 sewage sludge conditioning 174:199 Red mud was evaluated as an alternative skeleton builder combined with Fenton's reagent in sewage sludge conditioning. 24810740 1 66 theme alternative 111:121 arg1 builder 132:138 an alternative skeleton builder 108:138 an alternative skeleton builder combined with Fenton's reagent in sewage sludge conditioning 108:199 Red mud was evaluated as an alternative skeleton builder combined with Fenton's reagent in sewage sludge conditioning. 24810740 1 66 theme alternative 111:121 arg1 mud 87:89 Red mud 83:89 Red mud 83:89 Red mud was evaluated as an alternative skeleton builder combined with Fenton's reagent in sewage sludge conditioning. 24810740 6 67 theme ordinary 1552:1559 arg1 cement 1570:1575 ordinary Portland cement 1552:1575 ordinary Portland cement 1552:1575 The economic assessment for a wastewater treatment plant of 370,000 equivalent inhabitants confirms that using red mud conditioning, combined with Fenton's reagent, leads to a saving of approximately 411,000 USD/y or 50.8 USD/t DS comparing with using lime and ordinary Portland cement combined with Fenton's reagent, and approximately 612,000 USD/y or 75.5 USD/t DS comparing with the traditional treatment. 24810740 6 68 theme USD/t 1513:1517 arg1 DS 1519:1520 50.8 USD/t DS 1508:1520 50.8 USD/t DS 1508:1520 The economic assessment for a wastewater treatment plant of 370,000 equivalent inhabitants confirms that using red mud conditioning, combined with Fenton's reagent, leads to a saving of approximately 411,000 USD/y or 50.8 USD/t DS comparing with using lime and ordinary Portland cement combined with Fenton's reagent, and approximately 612,000 USD/y or 75.5 USD/t DS comparing with the traditional treatment. 24810740 4 69 theme conditioner 663:673 arg1 mechanism 636:644 The mechanism 632:644 The mechanism of the composite conditioner 632:673 The mechanism of the composite conditioner could be illuminated as follows: (1) extracellular polymeric substances (EPS), including loosely bound EPS and tightly bound EPS, were degraded into dissolved organics, e.g., proteins and polysaccharides; (2) bound water was released and converted into free water due to the degradation of EPS; and (3) morphology of the conditioned sludge exhibited a porous structure in contrast with the compact structure of raw sludge, and the addition of red mud formed new mineral phases and a rigid lattice structure in sludge, allowing the outflow of free water. 24810740 6 70 theme wastewater 1321:1330 arg1 plant 1342:1346 a wastewater treatment plant 1319:1346 a wastewater treatment plant 1319:1346 The economic assessment for a wastewater treatment plant of 370,000 equivalent inhabitants confirms that using red mud conditioning, combined with Fenton's reagent, leads to a saving of approximately 411,000 USD/y or 50.8 USD/t DS comparing with using lime and ordinary Portland cement combined with Fenton's reagent, and approximately 612,000 USD/y or 75.5 USD/t DS comparing with the traditional treatment. 24810740 1 71 theme skeleton 123:130 arg1 builder 132:138 an alternative skeleton builder 108:138 an alternative skeleton builder combined with Fenton's reagent in sewage sludge conditioning 108:199 Red mud was evaluated as an alternative skeleton builder combined with Fenton's reagent in sewage sludge conditioning. 24810740 1 71 theme skeleton 123:130 arg1 mud 87:89 Red mud 83:89 Red mud 83:89 Red mud was evaluated as an alternative skeleton builder combined with Fenton's reagent in sewage sludge conditioning. 26670328 0 0 theme Transrepression 108:122 arg1 Sensitivity 60:70 Sensitivity 60:70 Sensitivity of Glucocorticoid Receptor-Mediated Transrepression 60:122 Pharmacological Inhibition of O-GlcNAcase Does Not Increase Sensitivity of Glucocorticoid Receptor-Mediated Transrepression. 26670328 2 1 theme β-N-acetylglucosamine 549:569 arg1 group 582:586 an O-linked β-N-acetylglucosamine (O-GlcNAc) group 537:586 an O-linked β-N-acetylglucosamine (O-GlcNAc) group 537:586 Recent studies have shown that overexpression of O-linked β-N-acetylglucosamine transferase (OGT), which adds an O-linked β-N-acetylglucosamine (O-GlcNAc) group to the C-terminal domain of RNA pol II, increases the transrepression effects of glucocorticoids (GC). 26670328 3 2 theme O-GlcNAcylated 752:765 arg1 proteins 767:774 O-GlcNAcylated proteins 752:774 O-GlcNAcylated proteins 752:774 As O-GlcNAcase (OGA) is an enzyme that removes O-GlcNAc from O-GlcNAcylated proteins, we hypothesized that the potentiation of GC effects following OGT overexpression could be similarly observed via the direct inhibition of OGA, inhibiting O-GlcNAc removal from pol II. 26670328 3 3 theme O-GlcNAc 931:938 arg1 removal 940:946 inhibiting O-GlcNAc removal 920:946 inhibiting O-GlcNAc removal from pol II 920:958 As O-GlcNAcase (OGA) is an enzyme that removes O-GlcNAc from O-GlcNAcylated proteins, we hypothesized that the potentiation of GC effects following OGT overexpression could be similarly observed via the direct inhibition of OGA, inhibiting O-GlcNAc removal from pol II. 26670328 3 3 theme O-GlcNAc 931:938 arg1 OGA 915:917 OGA 915:917 OGA 915:917 As O-GlcNAcase (OGA) is an enzyme that removes O-GlcNAc from O-GlcNAcylated proteins, we hypothesized that the potentiation of GC effects following OGT overexpression could be similarly observed via the direct inhibition of OGA, inhibiting O-GlcNAc removal from pol II. 26670328 0 4 theme Receptor-Mediated 90:106 arg1 Transrepression 108:122 Glucocorticoid Receptor-Mediated Transrepression 75:122 Glucocorticoid Receptor-Mediated Transrepression 75:122 Pharmacological Inhibition of O-GlcNAcase Does Not Increase Sensitivity of Glucocorticoid Receptor-Mediated Transrepression. 26670328 3 5 theme OGA 915:917 arg1 inhibition 901:910 the direct inhibition 890:910 the direct inhibition of OGA, inhibiting O-GlcNAc removal from pol II 890:958 As O-GlcNAcase (OGA) is an enzyme that removes O-GlcNAc from O-GlcNAcylated proteins, we hypothesized that the potentiation of GC effects following OGT overexpression could be similarly observed via the direct inhibition of OGA, inhibiting O-GlcNAc removal from pol II. 26670328 6 6 theme pharmacological 1467:1481 arg1 inhibition 1483:1492 pharmacological inhibition 1467:1492 pharmacological inhibition of OGA 1467:1499 Thus, despite evidence for O-GlcNAc modification of RNA pol II in GR-mediated transrepression, our data indicate that pharmacological inhibition of OGA does not potentiate or enhance glucocorticoid-mediated transrepression. 26670328 1 7 theme pol 418:420 arg1 polymerase 403:412 RNA polymerase II 399:415 RNA polymerase II (pol II) 399:424 Glucocorticoid signaling regulates target genes by multiple mechanisms, including the repression of transcriptional activities of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) though direct protein-protein interactions and subsequent O-GlcNAcylation of RNA polymerase II (pol II). 26670328 1 7 theme pol 418:420 arg1 II 422:423 pol II 418:423 pol II 418:423 Glucocorticoid signaling regulates target genes by multiple mechanisms, including the repression of transcriptional activities of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) though direct protein-protein interactions and subsequent O-GlcNAcylation of RNA polymerase II (pol II). 26670328 2 8 theme transrepression 642:656 arg1 effects 658:664 the transrepression effects 638:664 the transrepression effects of glucocorticoids (GC) 638:688 Recent studies have shown that overexpression of O-linked β-N-acetylglucosamine transferase (OGT), which adds an O-linked β-N-acetylglucosamine (O-GlcNAc) group to the C-terminal domain of RNA pol II, increases the transrepression effects of glucocorticoids (GC). 26670328 5 9 from apoptosis 1309:1317 arg1 lines 1342:1346 several cancer cell lines 1322:1346 several cancer cell lines 1322:1346 Furthermore, inhibition of OGA did not potentiate glucocorticoid-induced apoptosis in several cancer cell lines. 26670328 4 10 theme engagement 1022:1031 arg1 evidence 1003:1010 pharmacological evidence 987:1010 pharmacological evidence of target engagement by a selective small molecule inhibitor of OGA 987:1078 Here we show that despite pharmacological evidence of target engagement by a selective small molecule inhibitor of OGA, there is no evidence for a sensitizing effect on glucocorticoid-mediated effects on TNF-α promoter activity, or gene expression generally, in human cells. 26670328 6 11 theme pol 1405:1407 arg1 modification 1385:1396 O-GlcNAc modification 1376:1396 O-GlcNAc modification of RNA pol II in GR-mediated transrepression 1376:1441 Thus, despite evidence for O-GlcNAc modification of RNA pol II in GR-mediated transrepression, our data indicate that pharmacological inhibition of OGA does not potentiate or enhance glucocorticoid-mediated transrepression. 26670328 4 12 theme promoter 1171:1178 arg1 activity 1180:1187 TNF-α promoter activity 1165:1187 TNF-α promoter activity 1165:1187 Here we show that despite pharmacological evidence of target engagement by a selective small molecule inhibitor of OGA, there is no evidence for a sensitizing effect on glucocorticoid-mediated effects on TNF-α promoter activity, or gene expression generally, in human cells. 26670328 6 13 theme RNA 1401:1403 arg1 pol 1405:1407 RNA pol II 1401:1410 RNA pol II 1401:1410 Thus, despite evidence for O-GlcNAc modification of RNA pol II in GR-mediated transrepression, our data indicate that pharmacological inhibition of OGA does not potentiate or enhance glucocorticoid-mediated transrepression. 26670328 4 14 from effect 1120:1125 arg1 effects 1154:1160 glucocorticoid-mediated effects 1130:1160 glucocorticoid-mediated effects on TNF-α promoter activity 1130:1187 Here we show that despite pharmacological evidence of target engagement by a selective small molecule inhibitor of OGA, there is no evidence for a sensitizing effect on glucocorticoid-mediated effects on TNF-α promoter activity, or gene expression generally, in human cells. 26670328 4 15 from effects 1154:1160 arg1 activity 1180:1187 TNF-α promoter activity 1165:1187 TNF-α promoter activity 1165:1187 Here we show that despite pharmacological evidence of target engagement by a selective small molecule inhibitor of OGA, there is no evidence for a sensitizing effect on glucocorticoid-mediated effects on TNF-α promoter activity, or gene expression generally, in human cells. 26670328 2 16 theme O-linked 476:483 arg1 OGT 520:522 OGT 520:522 OGT 520:522 Recent studies have shown that overexpression of O-linked β-N-acetylglucosamine transferase (OGT), which adds an O-linked β-N-acetylglucosamine (O-GlcNAc) group to the C-terminal domain of RNA pol II, increases the transrepression effects of glucocorticoids (GC). 26670328 2 16 theme O-linked 476:483 arg1 transferase 507:517 O-linked β-N-acetylglucosamine transferase 476:517 O-linked β-N-acetylglucosamine transferase (OGT) 476:523 Recent studies have shown that overexpression of O-linked β-N-acetylglucosamine transferase (OGT), which adds an O-linked β-N-acetylglucosamine (O-GlcNAc) group to the C-terminal domain of RNA pol II, increases the transrepression effects of glucocorticoids (GC). 26670328 4 17 theme TNF-α 1165:1169 arg1 activity 1180:1187 TNF-α promoter activity 1165:1187 TNF-α promoter activity 1165:1187 Here we show that despite pharmacological evidence of target engagement by a selective small molecule inhibitor of OGA, there is no evidence for a sensitizing effect on glucocorticoid-mediated effects on TNF-α promoter activity, or gene expression generally, in human cells. 26670328 6 18 theme GR-mediated 1415:1425 arg1 transrepression 1427:1441 GR-mediated transrepression 1415:1441 GR-mediated transrepression 1415:1441 Thus, despite evidence for O-GlcNAc modification of RNA pol II in GR-mediated transrepression, our data indicate that pharmacological inhibition of OGA does not potentiate or enhance glucocorticoid-mediated transrepression. 26670328 4 19 theme glucocorticoid-mediated 1130:1152 arg1 effects 1154:1160 glucocorticoid-mediated effects 1130:1160 glucocorticoid-mediated effects on TNF-α promoter activity 1130:1187 Here we show that despite pharmacological evidence of target engagement by a selective small molecule inhibitor of OGA, there is no evidence for a sensitizing effect on glucocorticoid-mediated effects on TNF-α promoter activity, or gene expression generally, in human cells. 26670328 5 20 theme OGA 1263:1265 arg1 inhibition 1249:1258 inhibition 1249:1258 inhibition of OGA 1249:1265 Furthermore, inhibition of OGA did not potentiate glucocorticoid-induced apoptosis in several cancer cell lines. 26670328 6 21 theme OGA 1497:1499 arg1 inhibition 1483:1492 pharmacological inhibition 1467:1492 pharmacological inhibition of OGA 1467:1499 Thus, despite evidence for O-GlcNAc modification of RNA pol II in GR-mediated transrepression, our data indicate that pharmacological inhibition of OGA does not potentiate or enhance glucocorticoid-mediated transrepression. 26670328 2 22 theme O-linked 540:547 arg1 group 582:586 an O-linked β-N-acetylglucosamine (O-GlcNAc) group 537:586 an O-linked β-N-acetylglucosamine (O-GlcNAc) group 537:586 Recent studies have shown that overexpression of O-linked β-N-acetylglucosamine transferase (OGT), which adds an O-linked β-N-acetylglucosamine (O-GlcNAc) group to the C-terminal domain of RNA pol II, increases the transrepression effects of glucocorticoids (GC). 26670328 4 23 theme target 1015:1020 arg1 engagement 1022:1031 target engagement 1015:1031 target engagement by a selective small molecule inhibitor of OGA 1015:1078 Here we show that despite pharmacological evidence of target engagement by a selective small molecule inhibitor of OGA, there is no evidence for a sensitizing effect on glucocorticoid-mediated effects on TNF-α promoter activity, or gene expression generally, in human cells. 26670328 1 24 theme transcriptional 225:239 arg1 activities 241:250 transcriptional activities 225:250 transcriptional activities of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) though direct protein-protein interactions and subsequent O-GlcNAcylation of RNA polymerase II (pol II) 225:424 Glucocorticoid signaling regulates target genes by multiple mechanisms, including the repression of transcriptional activities of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) though direct protein-protein interactions and subsequent O-GlcNAcylation of RNA polymerase II (pol II). 26670328 0 25 theme Pharmacological 0:14 arg1 Inhibition 16:25 Pharmacological Inhibition 0:25 Pharmacological Inhibition of O-GlcNAcase 0:40 Pharmacological Inhibition of O-GlcNAcase Does Not Increase Sensitivity of Glucocorticoid Receptor-Mediated Transrepression. 26670328 1 26 theme direct 329:334 arg1 interactions 352:363 direct protein-protein interactions 329:363 direct protein-protein interactions 329:363 Glucocorticoid signaling regulates target genes by multiple mechanisms, including the repression of transcriptional activities of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) though direct protein-protein interactions and subsequent O-GlcNAcylation of RNA polymerase II (pol II). 26670328 2 27 theme glucocorticoids 669:683 arg1 effects 658:664 the transrepression effects 638:664 the transrepression effects of glucocorticoids (GC) 638:688 Recent studies have shown that overexpression of O-linked β-N-acetylglucosamine transferase (OGT), which adds an O-linked β-N-acetylglucosamine (O-GlcNAc) group to the C-terminal domain of RNA pol II, increases the transrepression effects of glucocorticoids (GC). 26670328 5 28 theme glucocorticoid-induced 1286:1307 arg1 apoptosis 1309:1317 glucocorticoid-induced apoptosis 1286:1317 glucocorticoid-induced apoptosis in several cancer cell lines 1286:1346 Furthermore, inhibition of OGA did not potentiate glucocorticoid-induced apoptosis in several cancer cell lines. 26670328 1 29 theme Glucocorticoid 125:138 arg1 signaling 140:148 Glucocorticoid signaling 125:148 Glucocorticoid signaling 125:148 Glucocorticoid signaling regulates target genes by multiple mechanisms, including the repression of transcriptional activities of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) though direct protein-protein interactions and subsequent O-GlcNAcylation of RNA polymerase II (pol II). 26670328 3 30 theme effects 821:827 arg1 potentiation 802:813 the potentiation 798:813 the potentiation of GC effects following OGT overexpression 798:856 As O-GlcNAcase (OGA) is an enzyme that removes O-GlcNAc from O-GlcNAcylated proteins, we hypothesized that the potentiation of GC effects following OGT overexpression could be similarly observed via the direct inhibition of OGA, inhibiting O-GlcNAc removal from pol II. 26670328 1 31 theme activities 241:250 arg1 repression 211:220 the repression 207:220 the repression of transcriptional activities of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) though direct protein-protein interactions and subsequent O-GlcNAcylation of RNA polymerase II (pol II) 207:424 Glucocorticoid signaling regulates target genes by multiple mechanisms, including the repression of transcriptional activities of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) though direct protein-protein interactions and subsequent O-GlcNAcylation of RNA polymerase II (pol II). 26670328 0 32 theme O-GlcNAcase 30:40 arg1 Inhibition 16:25 Pharmacological Inhibition 0:25 Pharmacological Inhibition of O-GlcNAcase 0:40 Pharmacological Inhibition of O-GlcNAcase Does Not Increase Sensitivity of Glucocorticoid Receptor-Mediated Transrepression. 26670328 1 33 theme protein-protein 336:350 arg1 interactions 352:363 direct protein-protein interactions 329:363 direct protein-protein interactions 329:363 Glucocorticoid signaling regulates target genes by multiple mechanisms, including the repression of transcriptional activities of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) though direct protein-protein interactions and subsequent O-GlcNAcylation of RNA polymerase II (pol II). 26670328 2 34 theme RNA 616:618 arg1 pol 620:622 RNA pol II 616:625 RNA pol II 616:625 Recent studies have shown that overexpression of O-linked β-N-acetylglucosamine transferase (OGT), which adds an O-linked β-N-acetylglucosamine (O-GlcNAc) group to the C-terminal domain of RNA pol II, increases the transrepression effects of glucocorticoids (GC). 26670328 2 35 theme β-N-acetylglucosamine 485:505 arg1 OGT 520:522 OGT 520:522 OGT 520:522 Recent studies have shown that overexpression of O-linked β-N-acetylglucosamine transferase (OGT), which adds an O-linked β-N-acetylglucosamine (O-GlcNAc) group to the C-terminal domain of RNA pol II, increases the transrepression effects of glucocorticoids (GC). 26670328 2 35 theme β-N-acetylglucosamine 485:505 arg1 transferase 507:517 O-linked β-N-acetylglucosamine transferase 476:517 O-linked β-N-acetylglucosamine transferase (OGT) 476:523 Recent studies have shown that overexpression of O-linked β-N-acetylglucosamine transferase (OGT), which adds an O-linked β-N-acetylglucosamine (O-GlcNAc) group to the C-terminal domain of RNA pol II, increases the transrepression effects of glucocorticoids (GC). 26670328 2 36 theme transferase 507:517 arg1 overexpression 458:471 overexpression 458:471 overexpression of O-linked β-N-acetylglucosamine transferase (OGT), which adds an O-linked β-N-acetylglucosamine (O-GlcNAc) group to the C-terminal domain of RNA pol II, 458:626 Recent studies have shown that overexpression of O-linked β-N-acetylglucosamine transferase (OGT), which adds an O-linked β-N-acetylglucosamine (O-GlcNAc) group to the C-terminal domain of RNA pol II, increases the transrepression effects of glucocorticoids (GC). 26670328 6 37 from modification 1385:1396 arg1 transrepression 1427:1441 GR-mediated transrepression 1415:1441 GR-mediated transrepression 1415:1441 Thus, despite evidence for O-GlcNAc modification of RNA pol II in GR-mediated transrepression, our data indicate that pharmacological inhibition of OGA does not potentiate or enhance glucocorticoid-mediated transrepression. 26670328 6 38 theme O-GlcNAc 1376:1383 arg1 modification 1385:1396 O-GlcNAc modification 1376:1396 O-GlcNAc modification of RNA pol II in GR-mediated transrepression 1376:1441 Thus, despite evidence for O-GlcNAc modification of RNA pol II in GR-mediated transrepression, our data indicate that pharmacological inhibition of OGA does not potentiate or enhance glucocorticoid-mediated transrepression. 26670328 1 39 theme nuclear 255:261 arg1 NF-κB 315:319 NF-κB 315:319 NF-κB 315:319 Glucocorticoid signaling regulates target genes by multiple mechanisms, including the repression of transcriptional activities of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) though direct protein-protein interactions and subsequent O-GlcNAcylation of RNA polymerase II (pol II). 26670328 1 39 theme nuclear 255:261 arg1 κ-light-chain-enhancer 270:291 nuclear factor κ-light-chain-enhancer 255:291 nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) though direct protein-protein interactions and subsequent O-GlcNAcylation of RNA polymerase II (pol II) 255:424 Glucocorticoid signaling regulates target genes by multiple mechanisms, including the repression of transcriptional activities of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) though direct protein-protein interactions and subsequent O-GlcNAcylation of RNA polymerase II (pol II). 26670328 4 40 theme selective 1038:1046 arg1 inhibitor 1063:1071 a selective small molecule inhibitor 1036:1071 a selective small molecule inhibitor of OGA 1036:1078 Here we show that despite pharmacological evidence of target engagement by a selective small molecule inhibitor of OGA, there is no evidence for a sensitizing effect on glucocorticoid-mediated effects on TNF-α promoter activity, or gene expression generally, in human cells. 26670328 6 41 mod modification 1385:1396 arg1 pol 1405:1407 RNA pol II 1401:1410 RNA pol II 1401:1410 Thus, despite evidence for O-GlcNAc modification of RNA pol II in GR-mediated transrepression, our data indicate that pharmacological inhibition of OGA does not potentiate or enhance glucocorticoid-mediated transrepression. 26670328 6 41 mod modification 1385:1396 arg3 O-GlcNAc 1376:1383 O-GlcNAc modification 1376:1396 O-GlcNAc modification of RNA pol II in GR-mediated transrepression 1376:1441 Thus, despite evidence for O-GlcNAc modification of RNA pol II in GR-mediated transrepression, our data indicate that pharmacological inhibition of OGA does not potentiate or enhance glucocorticoid-mediated transrepression. 26670328 4 42 theme sensitizing 1108:1118 arg1 effect 1120:1125 a sensitizing effect 1106:1125 a sensitizing effect on glucocorticoid-mediated effects on TNF-α promoter activity 1106:1187 Here we show that despite pharmacological evidence of target engagement by a selective small molecule inhibitor of OGA, there is no evidence for a sensitizing effect on glucocorticoid-mediated effects on TNF-α promoter activity, or gene expression generally, in human cells. 26670328 1 43 theme factor 263:268 arg1 NF-κB 315:319 NF-κB 315:319 NF-κB 315:319 Glucocorticoid signaling regulates target genes by multiple mechanisms, including the repression of transcriptional activities of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) though direct protein-protein interactions and subsequent O-GlcNAcylation of RNA polymerase II (pol II). 26670328 1 43 theme factor 263:268 arg1 κ-light-chain-enhancer 270:291 nuclear factor κ-light-chain-enhancer 255:291 nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) though direct protein-protein interactions and subsequent O-GlcNAcylation of RNA polymerase II (pol II) 255:424 Glucocorticoid signaling regulates target genes by multiple mechanisms, including the repression of transcriptional activities of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) though direct protein-protein interactions and subsequent O-GlcNAcylation of RNA polymerase II (pol II). 26670328 1 44 theme subsequent 369:378 arg1 O-GlcNAcylation 380:394 subsequent O-GlcNAcylation 369:394 subsequent O-GlcNAcylation of RNA polymerase II (pol II) 369:424 Glucocorticoid signaling regulates target genes by multiple mechanisms, including the repression of transcriptional activities of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) though direct protein-protein interactions and subsequent O-GlcNAcylation of RNA polymerase II (pol II). 26670328 2 45 theme C-terminal 595:604 arg1 domain 606:611 the C-terminal domain 591:611 the C-terminal domain of RNA pol II 591:625 Recent studies have shown that overexpression of O-linked β-N-acetylglucosamine transferase (OGT), which adds an O-linked β-N-acetylglucosamine (O-GlcNAc) group to the C-terminal domain of RNA pol II, increases the transrepression effects of glucocorticoids (GC). 26670328 2 45 theme C-terminal 595:604 arg1 pol 620:622 RNA pol II 616:625 RNA pol II 616:625 Recent studies have shown that overexpression of O-linked β-N-acetylglucosamine transferase (OGT), which adds an O-linked β-N-acetylglucosamine (O-GlcNAc) group to the C-terminal domain of RNA pol II, increases the transrepression effects of glucocorticoids (GC). 26670328 3 46 from proteins 767:774 arg1 O-GlcNAc 738:745 O-GlcNAc 738:745 O-GlcNAc from O-GlcNAcylated proteins 738:774 As O-GlcNAcase (OGA) is an enzyme that removes O-GlcNAc from O-GlcNAcylated proteins, we hypothesized that the potentiation of GC effects following OGT overexpression could be similarly observed via the direct inhibition of OGA, inhibiting O-GlcNAc removal from pol II. 26670328 1 47 theme κ-light-chain-enhancer 270:291 arg1 activities 241:250 transcriptional activities 225:250 transcriptional activities of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) though direct protein-protein interactions and subsequent O-GlcNAcylation of RNA polymerase II (pol II) 225:424 Glucocorticoid signaling regulates target genes by multiple mechanisms, including the repression of transcriptional activities of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) though direct protein-protein interactions and subsequent O-GlcNAcylation of RNA polymerase II (pol II). 26670328 4 48 theme molecule 1054:1061 arg1 inhibitor 1063:1071 a selective small molecule inhibitor 1036:1071 a selective small molecule inhibitor of OGA 1036:1078 Here we show that despite pharmacological evidence of target engagement by a selective small molecule inhibitor of OGA, there is no evidence for a sensitizing effect on glucocorticoid-mediated effects on TNF-α promoter activity, or gene expression generally, in human cells. 26670328 3 49 theme GC 818:819 arg1 effects 821:827 GC effects 818:827 GC effects 818:827 As O-GlcNAcase (OGA) is an enzyme that removes O-GlcNAc from O-GlcNAcylated proteins, we hypothesized that the potentiation of GC effects following OGT overexpression could be similarly observed via the direct inhibition of OGA, inhibiting O-GlcNAc removal from pol II. 26670328 2 50 link O-linked 540:547 arg1 group 582:586 an O-linked β-N-acetylglucosamine (O-GlcNAc) group 537:586 an O-linked β-N-acetylglucosamine (O-GlcNAc) group 537:586 Recent studies have shown that overexpression of O-linked β-N-acetylglucosamine transferase (OGT), which adds an O-linked β-N-acetylglucosamine (O-GlcNAc) group to the C-terminal domain of RNA pol II, increases the transrepression effects of glucocorticoids (GC). 26670328 1 51 theme target 160:165 arg1 genes 167:171 target genes 160:171 target genes 160:171 Glucocorticoid signaling regulates target genes by multiple mechanisms, including the repression of transcriptional activities of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) though direct protein-protein interactions and subsequent O-GlcNAcylation of RNA polymerase II (pol II). 26670328 4 52 theme small 1048:1052 arg1 inhibitor 1063:1071 a selective small molecule inhibitor 1036:1071 a selective small molecule inhibitor of OGA 1036:1078 Here we show that despite pharmacological evidence of target engagement by a selective small molecule inhibitor of OGA, there is no evidence for a sensitizing effect on glucocorticoid-mediated effects on TNF-α promoter activity, or gene expression generally, in human cells. 26670328 6 53 theme glucocorticoid-mediated 1532:1554 arg1 transrepression 1556:1570 glucocorticoid-mediated transrepression 1532:1570 glucocorticoid-mediated transrepression 1532:1570 Thus, despite evidence for O-GlcNAc modification of RNA pol II in GR-mediated transrepression, our data indicate that pharmacological inhibition of OGA does not potentiate or enhance glucocorticoid-mediated transrepression. 26670328 5 54 theme several 1322:1328 arg1 lines 1342:1346 several cancer cell lines 1322:1346 several cancer cell lines 1322:1346 Furthermore, inhibition of OGA did not potentiate glucocorticoid-induced apoptosis in several cancer cell lines. 26670328 1 55 theme RNA 399:401 arg1 polymerase 403:412 RNA polymerase II 399:415 RNA polymerase II (pol II) 399:424 Glucocorticoid signaling regulates target genes by multiple mechanisms, including the repression of transcriptional activities of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) though direct protein-protein interactions and subsequent O-GlcNAcylation of RNA polymerase II (pol II). 26670328 1 55 theme RNA 399:401 arg1 II 422:423 pol II 418:423 pol II 418:423 Glucocorticoid signaling regulates target genes by multiple mechanisms, including the repression of transcriptional activities of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) though direct protein-protein interactions and subsequent O-GlcNAcylation of RNA polymerase II (pol II). 26670328 4 56 theme OGA 1076:1078 arg1 inhibitor 1063:1071 a selective small molecule inhibitor 1036:1071 a selective small molecule inhibitor of OGA 1036:1078 Here we show that despite pharmacological evidence of target engagement by a selective small molecule inhibitor of OGA, there is no evidence for a sensitizing effect on glucocorticoid-mediated effects on TNF-α promoter activity, or gene expression generally, in human cells. 26670328 4 57 theme human 1223:1227 arg1 cells 1229:1233 human cells 1223:1233 human cells 1223:1233 Here we show that despite pharmacological evidence of target engagement by a selective small molecule inhibitor of OGA, there is no evidence for a sensitizing effect on glucocorticoid-mediated effects on TNF-α promoter activity, or gene expression generally, in human cells. 26670328 5 58 theme cancer 1330:1335 arg1 lines 1342:1346 several cancer cell lines 1322:1346 several cancer cell lines 1322:1346 Furthermore, inhibition of OGA did not potentiate glucocorticoid-induced apoptosis in several cancer cell lines. 26670328 2 59 theme pol 620:622 arg1 domain 606:611 the C-terminal domain 591:611 the C-terminal domain of RNA pol II 591:625 Recent studies have shown that overexpression of O-linked β-N-acetylglucosamine transferase (OGT), which adds an O-linked β-N-acetylglucosamine (O-GlcNAc) group to the C-terminal domain of RNA pol II, increases the transrepression effects of glucocorticoids (GC). 26670328 2 59 theme pol 620:622 arg1 pol 620:622 RNA pol II 616:625 RNA pol II 616:625 Recent studies have shown that overexpression of O-linked β-N-acetylglucosamine transferase (OGT), which adds an O-linked β-N-acetylglucosamine (O-GlcNAc) group to the C-terminal domain of RNA pol II, increases the transrepression effects of glucocorticoids (GC). 26670328 4 60 theme gene 1193:1196 arg1 expression 1198:1207 gene expression 1193:1207 gene expression 1193:1207 Here we show that despite pharmacological evidence of target engagement by a selective small molecule inhibitor of OGA, there is no evidence for a sensitizing effect on glucocorticoid-mediated effects on TNF-α promoter activity, or gene expression generally, in human cells. 26670328 1 61 theme multiple 176:183 arg1 repression 211:220 the repression 207:220 the repression of transcriptional activities of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) though direct protein-protein interactions and subsequent O-GlcNAcylation of RNA polymerase II (pol II) 207:424 Glucocorticoid signaling regulates target genes by multiple mechanisms, including the repression of transcriptional activities of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) though direct protein-protein interactions and subsequent O-GlcNAcylation of RNA polymerase II (pol II). 26670328 1 61 theme multiple 176:183 arg1 mechanisms 185:194 multiple mechanisms 176:194 multiple mechanisms 176:194 Glucocorticoid signaling regulates target genes by multiple mechanisms, including the repression of transcriptional activities of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) though direct protein-protein interactions and subsequent O-GlcNAcylation of RNA polymerase II (pol II). 26670328 5 62 theme cell 1337:1340 arg1 lines 1342:1346 several cancer cell lines 1322:1346 several cancer cell lines 1322:1346 Furthermore, inhibition of OGA did not potentiate glucocorticoid-induced apoptosis in several cancer cell lines. 26670328 1 63 theme activated 296:304 arg1 cells 308:312 activated B cells 296:312 activated B cells 296:312 Glucocorticoid signaling regulates target genes by multiple mechanisms, including the repression of transcriptional activities of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) though direct protein-protein interactions and subsequent O-GlcNAcylation of RNA polymerase II (pol II). 26670328 2 64 theme O-GlcNAc 572:579 arg1 group 582:586 an O-linked β-N-acetylglucosamine (O-GlcNAc) group 537:586 an O-linked β-N-acetylglucosamine (O-GlcNAc) group 537:586 Recent studies have shown that overexpression of O-linked β-N-acetylglucosamine transferase (OGT), which adds an O-linked β-N-acetylglucosamine (O-GlcNAc) group to the C-terminal domain of RNA pol II, increases the transrepression effects of glucocorticoids (GC). 26670328 2 65 link O-linked 476:483 arg1 OGT 520:522 OGT 520:522 OGT 520:522 Recent studies have shown that overexpression of O-linked β-N-acetylglucosamine transferase (OGT), which adds an O-linked β-N-acetylglucosamine (O-GlcNAc) group to the C-terminal domain of RNA pol II, increases the transrepression effects of glucocorticoids (GC). 26670328 2 65 link O-linked 476:483 arg1 transferase 507:517 O-linked β-N-acetylglucosamine transferase 476:517 O-linked β-N-acetylglucosamine transferase (OGT) 476:523 Recent studies have shown that overexpression of O-linked β-N-acetylglucosamine transferase (OGT), which adds an O-linked β-N-acetylglucosamine (O-GlcNAc) group to the C-terminal domain of RNA pol II, increases the transrepression effects of glucocorticoids (GC). 26670328 3 66 from pol 953:955 arg1 removal 940:946 inhibiting O-GlcNAc removal 920:946 inhibiting O-GlcNAc removal from pol II 920:958 As O-GlcNAcase (OGA) is an enzyme that removes O-GlcNAc from O-GlcNAcylated proteins, we hypothesized that the potentiation of GC effects following OGT overexpression could be similarly observed via the direct inhibition of OGA, inhibiting O-GlcNAc removal from pol II. 26670328 3 66 from pol 953:955 arg1 OGA 915:917 OGA 915:917 OGA 915:917 As O-GlcNAcase (OGA) is an enzyme that removes O-GlcNAc from O-GlcNAcylated proteins, we hypothesized that the potentiation of GC effects following OGT overexpression could be similarly observed via the direct inhibition of OGA, inhibiting O-GlcNAc removal from pol II. 26670328 2 67 theme Recent 427:432 arg1 studies 434:440 Recent studies 427:440 Recent studies 427:440 Recent studies have shown that overexpression of O-linked β-N-acetylglucosamine transferase (OGT), which adds an O-linked β-N-acetylglucosamine (O-GlcNAc) group to the C-terminal domain of RNA pol II, increases the transrepression effects of glucocorticoids (GC). 26670328 3 68 theme direct 894:899 arg1 inhibition 901:910 the direct inhibition 890:910 the direct inhibition of OGA, inhibiting O-GlcNAc removal from pol II 890:958 As O-GlcNAcase (OGA) is an enzyme that removes O-GlcNAc from O-GlcNAcylated proteins, we hypothesized that the potentiation of GC effects following OGT overexpression could be similarly observed via the direct inhibition of OGA, inhibiting O-GlcNAc removal from pol II. 26670328 1 69 theme B 306:306 arg1 cells 308:312 activated B cells 296:312 activated B cells 296:312 Glucocorticoid signaling regulates target genes by multiple mechanisms, including the repression of transcriptional activities of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) though direct protein-protein interactions and subsequent O-GlcNAcylation of RNA polymerase II (pol II). 26670328 1 70 theme polymerase 403:412 arg1 interactions 352:363 direct protein-protein interactions 329:363 direct protein-protein interactions 329:363 Glucocorticoid signaling regulates target genes by multiple mechanisms, including the repression of transcriptional activities of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) though direct protein-protein interactions and subsequent O-GlcNAcylation of RNA polymerase II (pol II). 26670328 1 70 theme polymerase 403:412 arg1 O-GlcNAcylation 380:394 subsequent O-GlcNAcylation 369:394 subsequent O-GlcNAcylation of RNA polymerase II (pol II) 369:424 Glucocorticoid signaling regulates target genes by multiple mechanisms, including the repression of transcriptional activities of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) though direct protein-protein interactions and subsequent O-GlcNAcylation of RNA polymerase II (pol II). 26670328 3 71 theme OGT 839:841 arg1 overexpression 843:856 OGT overexpression 839:856 OGT overexpression 839:856 As O-GlcNAcase (OGA) is an enzyme that removes O-GlcNAc from O-GlcNAcylated proteins, we hypothesized that the potentiation of GC effects following OGT overexpression could be similarly observed via the direct inhibition of OGA, inhibiting O-GlcNAc removal from pol II. 26670328 4 72 theme pharmacological 987:1001 arg1 evidence 1003:1010 pharmacological evidence 987:1010 pharmacological evidence of target engagement by a selective small molecule inhibitor of OGA 987:1078 Here we show that despite pharmacological evidence of target engagement by a selective small molecule inhibitor of OGA, there is no evidence for a sensitizing effect on glucocorticoid-mediated effects on TNF-α promoter activity, or gene expression generally, in human cells. 26670328 3 73 theme inhibiting 920:929 arg1 removal 940:946 inhibiting O-GlcNAc removal 920:946 inhibiting O-GlcNAc removal from pol II 920:958 As O-GlcNAcase (OGA) is an enzyme that removes O-GlcNAc from O-GlcNAcylated proteins, we hypothesized that the potentiation of GC effects following OGT overexpression could be similarly observed via the direct inhibition of OGA, inhibiting O-GlcNAc removal from pol II. 26670328 3 73 theme inhibiting 920:929 arg1 OGA 915:917 OGA 915:917 OGA 915:917 As O-GlcNAcase (OGA) is an enzyme that removes O-GlcNAc from O-GlcNAcylated proteins, we hypothesized that the potentiation of GC effects following OGT overexpression could be similarly observed via the direct inhibition of OGA, inhibiting O-GlcNAc removal from pol II. 26670328 1 74 theme cells 308:312 arg1 NF-κB 315:319 NF-κB 315:319 NF-κB 315:319 Glucocorticoid signaling regulates target genes by multiple mechanisms, including the repression of transcriptional activities of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) though direct protein-protein interactions and subsequent O-GlcNAcylation of RNA polymerase II (pol II). 26670328 1 74 theme cells 308:312 arg1 κ-light-chain-enhancer 270:291 nuclear factor κ-light-chain-enhancer 255:291 nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) though direct protein-protein interactions and subsequent O-GlcNAcylation of RNA polymerase II (pol II) 255:424 Glucocorticoid signaling regulates target genes by multiple mechanisms, including the repression of transcriptional activities of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) though direct protein-protein interactions and subsequent O-GlcNAcylation of RNA polymerase II (pol II). 27032029 9 0 from negligible 1402:1411 arg1 jejunum 1420:1426 jejunum 1420:1426 jejunum 1420:1426 Specialised bacterial groups like Prevotella and Ruminococcaceae were among the most predominant ones found in the colon, as they possess cellulolytic properties to degrade (at least partially) non-starch polysaccharides, while their abundance was negligible in the jejunum and the ileum. 27032029 9 0 from negligible 1402:1411 arg1 ileum 1436:1440 the ileum 1432:1440 the ileum 1432:1440 Specialised bacterial groups like Prevotella and Ruminococcaceae were among the most predominant ones found in the colon, as they possess cellulolytic properties to degrade (at least partially) non-starch polysaccharides, while their abundance was negligible in the jejunum and the ileum. 27032029 12 1 theme intestinal 1944:1953 arg1 composition 1965:1975 intestinal microbial composition 1944:1975 intestinal microbial composition 1944:1975 Based on these findings, a more in-depth view on intestinal microbial composition within the gastrointestinal tract of young pigs fed with low- and high-fibre diets was generated. 27032029 10 2 dep jejunum 1573:1579 arg1 the 1569:1571 the 1569:1571 the 1569:1571 Conversely, the genera Lactobacillus, Bifidobacterium and Veillonella, for example, were among the most predominant groups in the jejunum and ileum, while in the colon they were hardly found. 27032029 8 3 theme other 1130:1134 arg1 segments 1144:1151 the other two gut segments 1126:1151 the other two gut segments 1126:1151 The parameters of alpha and beta diversity analysis showed significant differences (p < 0.01) between the colon and the other two gut segments. 27032029 11 4 from differences 1736:1746 arg1 abundance 1751:1759 abundance 1751:1759 abundance 1751:1759 Although statistical taxonomical evaluation, following p-value correction, did not reveal pronounced differences in abundance related to bran modification, alpha and beta diversity analysis showed an influence regarding the various feeding strategies applied. 27032029 7 5 located found 972:976 arg1 abundance 999:1007 high abundance 994:1007 high abundance 994:1007 While Firmicutes were most predominant in all three gut segments, Bacteroidetes were additionally found in the colon at high abundance. 27032029 7 5 located found 972:976 arg2 Bacteroidetes 940:952 Bacteroidetes 940:952 Bacteroidetes 940:952 While Firmicutes were most predominant in all three gut segments, Bacteroidetes were additionally found in the colon at high abundance. 27032029 7 5 located found 972:976 arg1 colon 985:989 the colon 981:989 the colon 981:989 While Firmicutes were most predominant in all three gut segments, Bacteroidetes were additionally found in the colon at high abundance. 27032029 9 6 theme Specialised 1154:1164 arg1 groups 1176:1181 Specialised bacterial groups 1154:1181 Specialised bacterial groups like Prevotella and Ruminococcaceae 1154:1217 Specialised bacterial groups like Prevotella and Ruminococcaceae were among the most predominant ones found in the colon, as they possess cellulolytic properties to degrade (at least partially) non-starch polysaccharides, while their abundance was negligible in the jejunum and the ileum. 27032029 8 7 theme gut 1140:1142 arg1 segments 1144:1151 the other two gut segments 1126:1151 the other two gut segments 1126:1151 The parameters of alpha and beta diversity analysis showed significant differences (p < 0.01) between the colon and the other two gut segments. 27032029 6 8 theme location-specific 818:834 arg1 differences 836:846 distinct location-specific differences 809:846 distinct location-specific differences in microbial composition 809:871 The obtained results revealed distinct location-specific differences in microbial composition. 27032029 4 9 theme digesta 614:620 arg1 samples 622:628 digesta samples 614:628 digesta samples from the jejunum 614:645 Total DNA was extracted from digesta samples from the jejunum, the end of the ileum and the colon ascendens. 27032029 10 10 theme predominant 1547:1557 arg1 groups 1559:1564 the most predominant groups 1538:1564 the most predominant groups 1538:1564 Conversely, the genera Lactobacillus, Bifidobacterium and Veillonella, for example, were among the most predominant groups in the jejunum and ileum, while in the colon they were hardly found. 27032029 1 11 theme Control 180:186 arg1 diet 188:191 a Control diet 178:191 a Control diet low in dietary fibre and modified wheat bran variants 178:245 The intestinal microbiota of piglets fed with a Control diet low in dietary fibre and modified wheat bran variants as an additional source of insoluble dietary fibre was characterised. 27032029 0 12 theme amplicon 111:118 arg1 sequencing 120:129 rRNA next-generation amplicon sequencing 90:129 rRNA next-generation amplicon sequencing 90:129 The intestinal microbiota of piglets fed with wheat bran variants as characterised by 16S rRNA next-generation amplicon sequencing. 27032029 1 13 theme low 193:195 arg1 diet 188:191 a Control diet 178:191 a Control diet low in dietary fibre and modified wheat bran variants 178:245 The intestinal microbiota of piglets fed with a Control diet low in dietary fibre and modified wheat bran variants as an additional source of insoluble dietary fibre was characterised. 27032029 12 14 theme low- 2034:2037 arg1 diets 2054:2058 low- and high-fibre diets 2034:2058 low- and high-fibre diets 2034:2058 Based on these findings, a more in-depth view on intestinal microbial composition within the gastrointestinal tract of young pigs fed with low- and high-fibre diets was generated. 27032029 7 15 from predominant 901:911 arg1 segments 930:937 all three gut segments 916:937 all three gut segments 916:937 While Firmicutes were most predominant in all three gut segments, Bacteroidetes were additionally found in the colon at high abundance. 27032029 10 16 located found 1628:1632 arg1 colon 1605:1609 the colon 1601:1609 the colon 1601:1609 Conversely, the genera Lactobacillus, Bifidobacterium and Veillonella, for example, were among the most predominant groups in the jejunum and ileum, while in the colon they were hardly found. 27032029 10 16 located found 1628:1632 arg2 they 1611:1614 they 1611:1614 they 1611:1614 Conversely, the genera Lactobacillus, Bifidobacterium and Veillonella, for example, were among the most predominant groups in the jejunum and ileum, while in the colon they were hardly found. 27032029 12 17 theme high-fibre 2043:2052 arg1 diets 2054:2058 low- and high-fibre diets 2034:2058 low- and high-fibre diets 2034:2058 Based on these findings, a more in-depth view on intestinal microbial composition within the gastrointestinal tract of young pigs fed with low- and high-fibre diets was generated. 27032029 12 18 theme young 2014:2018 arg1 pigs 2020:2023 young pigs 2014:2023 young pigs fed with low- and high-fibre diets 2014:2058 Based on these findings, a more in-depth view on intestinal microbial composition within the gastrointestinal tract of young pigs fed with low- and high-fibre diets was generated. 27032029 0 19 theme bran 52:55 arg1 variants 57:64 wheat bran variants 46:64 wheat bran variants 46:64 The intestinal microbiota of piglets fed with wheat bran variants as characterised by 16S rRNA next-generation amplicon sequencing. 27032029 3 20 theme animals 561:567 arg1 piglets 549:555 48 piglets 546:555 48 piglets (12 animals per treatment) 546:582 Wheat bran was either included in its native form or modified by fermentation and extrusion before added at 150 g/kg to a basal diet for 48 piglets (12 animals per treatment). 27032029 3 20 theme animals 561:567 arg1 treatment 573:581 12 animals per treatment 558:581 12 animals per treatment 558:581 Wheat bran was either included in its native form or modified by fermentation and extrusion before added at 150 g/kg to a basal diet for 48 piglets (12 animals per treatment). 27032029 7 21 theme high 994:997 arg1 abundance 999:1007 high abundance 994:1007 high abundance 994:1007 While Firmicutes were most predominant in all three gut segments, Bacteroidetes were additionally found in the colon at high abundance. 27032029 7 22 theme gut 926:928 arg1 segments 930:937 all three gut segments 916:937 all three gut segments 916:937 While Firmicutes were most predominant in all three gut segments, Bacteroidetes were additionally found in the colon at high abundance. 27032029 1 23 theme piglets 161:167 arg1 microbiota 147:156 The intestinal microbiota 132:156 The intestinal microbiota of piglets fed with a Control diet low in dietary fibre and modified wheat bran variants as an additional source of insoluble dietary fibre 132:296 The intestinal microbiota of piglets fed with a Control diet low in dietary fibre and modified wheat bran variants as an additional source of insoluble dietary fibre was characterised. 27032029 12 24 from view 1936:1939 arg1 composition 1965:1975 intestinal microbial composition 1944:1975 intestinal microbial composition 1944:1975 Based on these findings, a more in-depth view on intestinal microbial composition within the gastrointestinal tract of young pigs fed with low- and high-fibre diets was generated. 27032029 2 25 theme different 371:379 arg1 segments 385:392 three different gut segments 365:392 three different gut segments 365:392 In this context, variances in the microbiota of three different gut segments were assessed. 27032029 0 26 theme rRNA 90:93 arg1 sequencing 120:129 rRNA next-generation amplicon sequencing 90:129 rRNA next-generation amplicon sequencing 90:129 The intestinal microbiota of piglets fed with wheat bran variants as characterised by 16S rRNA next-generation amplicon sequencing. 27032029 4 27 theme ileum 663:667 arg1 ascendens 683:691 the colon ascendens 673:691 the colon ascendens 673:691 Total DNA was extracted from digesta samples from the jejunum, the end of the ileum and the colon ascendens. 27032029 4 27 theme ileum 663:667 arg1 samples 622:628 digesta samples 614:628 digesta samples from the jejunum 614:645 Total DNA was extracted from digesta samples from the jejunum, the end of the ileum and the colon ascendens. 27032029 4 27 theme ileum 663:667 arg1 end 652:654 the end 648:654 the end of the ileum 648:667 Total DNA was extracted from digesta samples from the jejunum, the end of the ileum and the colon ascendens. 27032029 1 28 theme additional 253:262 arg1 source 264:269 an additional source 250:269 an additional source of insoluble dietary fibre 250:296 The intestinal microbiota of piglets fed with a Control diet low in dietary fibre and modified wheat bran variants as an additional source of insoluble dietary fibre was characterised. 27032029 6 29 theme distinct 809:816 arg1 differences 836:846 distinct location-specific differences 809:846 distinct location-specific differences in microbial composition 809:871 The obtained results revealed distinct location-specific differences in microbial composition. 27032029 2 30 theme segments 385:392 arg1 microbiota 351:360 the microbiota 347:360 the microbiota of three different gut segments 347:392 In this context, variances in the microbiota of three different gut segments were assessed. 27032029 0 31 theme piglets 29:35 arg1 microbiota 15:24 The intestinal microbiota 0:24 The intestinal microbiota of piglets 0:35 The intestinal microbiota of piglets fed with wheat bran variants as characterised by 16S rRNA next-generation amplicon sequencing. 27032029 8 32 theme diversity 1043:1051 arg1 analysis 1053:1060 diversity analysis 1043:1060 diversity analysis 1043:1060 The parameters of alpha and beta diversity analysis showed significant differences (p < 0.01) between the colon and the other two gut segments. 27032029 11 33 theme beta 1801:1804 arg1 analysis 1816:1823 alpha and beta diversity analysis 1791:1823 alpha and beta diversity analysis 1791:1823 Although statistical taxonomical evaluation, following p-value correction, did not reveal pronounced differences in abundance related to bran modification, alpha and beta diversity analysis showed an influence regarding the various feeding strategies applied. 27032029 9 34 from jejunum 1420:1426 arg1 negligible 1402:1411 negligible 1402:1411 negligible 1402:1411 Specialised bacterial groups like Prevotella and Ruminococcaceae were among the most predominant ones found in the colon, as they possess cellulolytic properties to degrade (at least partially) non-starch polysaccharides, while their abundance was negligible in the jejunum and the ileum. 27032029 9 35 contain possess 1284:1290 arg2 properties 1305:1314 cellulolytic properties 1292:1314 cellulolytic properties 1292:1314 Specialised bacterial groups like Prevotella and Ruminococcaceae were among the most predominant ones found in the colon, as they possess cellulolytic properties to degrade (at least partially) non-starch polysaccharides, while their abundance was negligible in the jejunum and the ileum. 27032029 9 35 contain possess 1284:1290 arg1 they 1279:1282 they 1279:1282 they 1279:1282 Specialised bacterial groups like Prevotella and Ruminococcaceae were among the most predominant ones found in the colon, as they possess cellulolytic properties to degrade (at least partially) non-starch polysaccharides, while their abundance was negligible in the jejunum and the ileum. 27032029 11 36 theme alpha 1791:1795 arg1 analysis 1816:1823 alpha and beta diversity analysis 1791:1823 alpha and beta diversity analysis 1791:1823 Although statistical taxonomical evaluation, following p-value correction, did not reveal pronounced differences in abundance related to bran modification, alpha and beta diversity analysis showed an influence regarding the various feeding strategies applied. 27032029 8 37 dep alpha 1028:1032 arg1 analysis 1053:1060 diversity analysis 1043:1060 diversity analysis 1043:1060 The parameters of alpha and beta diversity analysis showed significant differences (p < 0.01) between the colon and the other two gut segments. 27032029 11 38 theme taxonomical 1656:1666 arg1 evaluation 1668:1677 statistical taxonomical evaluation 1644:1677 statistical taxonomical evaluation 1644:1677 Although statistical taxonomical evaluation, following p-value correction, did not reveal pronounced differences in abundance related to bran modification, alpha and beta diversity analysis showed an influence regarding the various feeding strategies applied. 27032029 9 39 dep jejunum 1420:1426 arg1 the 1416:1418 the 1416:1418 the 1416:1418 Specialised bacterial groups like Prevotella and Ruminococcaceae were among the most predominant ones found in the colon, as they possess cellulolytic properties to degrade (at least partially) non-starch polysaccharides, while their abundance was negligible in the jejunum and the ileum. 27032029 9 40 theme non-starch 1348:1357 arg1 polysaccharides 1359:1373 (at least partially) non-starch polysaccharides 1327:1373 (at least partially) non-starch polysaccharides 1327:1373 Specialised bacterial groups like Prevotella and Ruminococcaceae were among the most predominant ones found in the colon, as they possess cellulolytic properties to degrade (at least partially) non-starch polysaccharides, while their abundance was negligible in the jejunum and the ileum. 27032029 12 41 theme pigs 2020:2023 arg1 tract 2005:2009 the gastrointestinal tract 1984:2009 the gastrointestinal tract of young pigs fed with low- and high-fibre diets 1984:2058 Based on these findings, a more in-depth view on intestinal microbial composition within the gastrointestinal tract of young pigs fed with low- and high-fibre diets was generated. 27032029 12 42 theme gastrointestinal 1988:2003 arg1 tract 2005:2009 the gastrointestinal tract 1984:2009 the gastrointestinal tract of young pigs fed with low- and high-fibre diets 1984:2058 Based on these findings, a more in-depth view on intestinal microbial composition within the gastrointestinal tract of young pigs fed with low- and high-fibre diets was generated. 27032029 10 43 from groups 1559:1564 arg1 ileum 1585:1589 ileum 1585:1589 ileum 1585:1589 Conversely, the genera Lactobacillus, Bifidobacterium and Veillonella, for example, were among the most predominant groups in the jejunum and ileum, while in the colon they were hardly found. 27032029 10 43 from groups 1559:1564 arg1 jejunum 1573:1579 jejunum 1573:1579 jejunum 1573:1579 Conversely, the genera Lactobacillus, Bifidobacterium and Veillonella, for example, were among the most predominant groups in the jejunum and ileum, while in the colon they were hardly found. 27032029 6 44 from differences 836:846 arg1 composition 861:871 microbial composition 851:871 microbial composition 851:871 The obtained results revealed distinct location-specific differences in microbial composition. 27032029 6 45 theme microbial 851:859 arg1 composition 861:871 microbial composition 851:871 microbial composition 851:871 The obtained results revealed distinct location-specific differences in microbial composition. 27032029 9 46 located found 1256:1260 arg2 ones 1251:1254 the most predominant ones 1230:1254 the most predominant ones found in the colon 1230:1273 Specialised bacterial groups like Prevotella and Ruminococcaceae were among the most predominant ones found in the colon, as they possess cellulolytic properties to degrade (at least partially) non-starch polysaccharides, while their abundance was negligible in the jejunum and the ileum. 27032029 9 46 located found 1256:1260 arg1 colon 1269:1273 the colon 1265:1273 the colon 1265:1273 Specialised bacterial groups like Prevotella and Ruminococcaceae were among the most predominant ones found in the colon, as they possess cellulolytic properties to degrade (at least partially) non-starch polysaccharides, while their abundance was negligible in the jejunum and the ileum. 27032029 12 47 theme microbial 1955:1963 arg1 composition 1965:1975 intestinal microbial composition 1944:1975 intestinal microbial composition 1944:1975 Based on these findings, a more in-depth view on intestinal microbial composition within the gastrointestinal tract of young pigs fed with low- and high-fibre diets was generated. 27032029 2 48 from variances 334:342 arg1 microbiota 351:360 the microbiota 347:360 the microbiota of three different gut segments 347:392 In this context, variances in the microbiota of three different gut segments were assessed. 27032029 9 49 theme bacterial 1166:1174 arg1 groups 1176:1181 Specialised bacterial groups 1154:1181 Specialised bacterial groups like Prevotella and Ruminococcaceae 1154:1217 Specialised bacterial groups like Prevotella and Ruminococcaceae were among the most predominant ones found in the colon, as they possess cellulolytic properties to degrade (at least partially) non-starch polysaccharides, while their abundance was negligible in the jejunum and the ileum. 27032029 3 50 theme basal 531:535 arg1 diet 537:540 a basal diet 529:540 a basal diet for 48 piglets (12 animals per treatment) 529:582 Wheat bran was either included in its native form or modified by fermentation and extrusion before added at 150 g/kg to a basal diet for 48 piglets (12 animals per treatment). 27032029 11 51 theme related 1761:1767 arg1 differences 1736:1746 pronounced differences 1725:1746 pronounced differences in abundance related to bran modification 1725:1788 Although statistical taxonomical evaluation, following p-value correction, did not reveal pronounced differences in abundance related to bran modification, alpha and beta diversity analysis showed an influence regarding the various feeding strategies applied. 27032029 5 52 theme Illumina 763:770 arg1 MiSeq 772:776 the Illumina MiSeq 759:776 the Illumina MiSeq 759:776 Samples were prepared accordingly for subsequent sequencing with the Illumina MiSeq. 27032029 12 53 theme in-depth 1927:1934 arg1 view 1936:1939 a more in-depth view 1920:1939 a more in-depth view on intestinal microbial composition within the gastrointestinal tract of young pigs fed with low- and high-fibre diets 1920:2058 Based on these findings, a more in-depth view on intestinal microbial composition within the gastrointestinal tract of young pigs fed with low- and high-fibre diets was generated. 27032029 5 54 with sequencing 743:752 arg1 MiSeq 772:776 the Illumina MiSeq 759:776 the Illumina MiSeq 759:776 Samples were prepared accordingly for subsequent sequencing with the Illumina MiSeq. 27032029 1 55 from bran 233:236 arg1 low 193:195 low 193:195 low 193:195 The intestinal microbiota of piglets fed with a Control diet low in dietary fibre and modified wheat bran variants as an additional source of insoluble dietary fibre was characterised. 27032029 1 56 dep fibre 208:212 arg1 variants 238:245 variants 238:245 variants 238:245 The intestinal microbiota of piglets fed with a Control diet low in dietary fibre and modified wheat bran variants as an additional source of insoluble dietary fibre was characterised. 27032029 4 57 theme Total 585:589 arg1 DNA 591:593 Total DNA 585:593 Total DNA 585:593 Total DNA was extracted from digesta samples from the jejunum, the end of the ileum and the colon ascendens. 27032029 11 58 theme bran 1772:1775 arg1 modification 1777:1788 bran modification 1772:1788 bran modification 1772:1788 Although statistical taxonomical evaluation, following p-value correction, did not reveal pronounced differences in abundance related to bran modification, alpha and beta diversity analysis showed an influence regarding the various feeding strategies applied. 27032029 1 59 from fibre 208:212 arg1 low 193:195 low 193:195 low 193:195 The intestinal microbiota of piglets fed with a Control diet low in dietary fibre and modified wheat bran variants as an additional source of insoluble dietary fibre was characterised. 27032029 3 60 theme per 569:571 arg1 piglets 549:555 48 piglets 546:555 48 piglets (12 animals per treatment) 546:582 Wheat bran was either included in its native form or modified by fermentation and extrusion before added at 150 g/kg to a basal diet for 48 piglets (12 animals per treatment). 27032029 3 60 theme per 569:571 arg1 treatment 573:581 12 animals per treatment 558:581 12 animals per treatment 558:581 Wheat bran was either included in its native form or modified by fermentation and extrusion before added at 150 g/kg to a basal diet for 48 piglets (12 animals per treatment). 27032029 1 61 from low 193:195 arg1 fibre 208:212 fibre 208:212 fibre 208:212 The intestinal microbiota of piglets fed with a Control diet low in dietary fibre and modified wheat bran variants as an additional source of insoluble dietary fibre was characterised. 27032029 1 61 from low 193:195 arg1 bran 233:236 modified wheat bran 218:236 modified wheat bran 218:236 The intestinal microbiota of piglets fed with a Control diet low in dietary fibre and modified wheat bran variants as an additional source of insoluble dietary fibre was characterised. 27032029 3 62 theme native 447:452 arg1 form 454:457 its native form 443:457 its native form 443:457 Wheat bran was either included in its native form or modified by fermentation and extrusion before added at 150 g/kg to a basal diet for 48 piglets (12 animals per treatment). 27032029 9 63 theme predominant 1239:1249 arg1 ones 1251:1254 the most predominant ones 1230:1254 the most predominant ones found in the colon 1230:1273 Specialised bacterial groups like Prevotella and Ruminococcaceae were among the most predominant ones found in the colon, as they possess cellulolytic properties to degrade (at least partially) non-starch polysaccharides, while their abundance was negligible in the jejunum and the ileum. 27032029 1 64 theme intestinal 136:145 arg1 microbiota 147:156 The intestinal microbiota 132:156 The intestinal microbiota of piglets fed with a Control diet low in dietary fibre and modified wheat bran variants as an additional source of insoluble dietary fibre 132:296 The intestinal microbiota of piglets fed with a Control diet low in dietary fibre and modified wheat bran variants as an additional source of insoluble dietary fibre was characterised. 27032029 11 65 theme p-value 1690:1696 arg1 correction 1698:1707 p-value correction 1690:1707 p-value correction 1690:1707 Although statistical taxonomical evaluation, following p-value correction, did not reveal pronounced differences in abundance related to bran modification, alpha and beta diversity analysis showed an influence regarding the various feeding strategies applied. 27032029 7 66 from segments 930:937 arg1 predominant 901:911 predominant 901:911 predominant 901:911 While Firmicutes were most predominant in all three gut segments, Bacteroidetes were additionally found in the colon at high abundance. 27032029 11 67 theme pronounced 1725:1734 arg1 differences 1736:1746 pronounced differences 1725:1746 pronounced differences in abundance related to bran modification 1725:1788 Although statistical taxonomical evaluation, following p-value correction, did not reveal pronounced differences in abundance related to bran modification, alpha and beta diversity analysis showed an influence regarding the various feeding strategies applied. 27032029 4 68 theme colon 677:681 arg1 ascendens 683:691 the colon ascendens 673:691 the colon ascendens 673:691 Total DNA was extracted from digesta samples from the jejunum, the end of the ileum and the colon ascendens. 27032029 0 69 theme next-generation 95:109 arg1 sequencing 120:129 rRNA next-generation amplicon sequencing 90:129 rRNA next-generation amplicon sequencing 90:129 The intestinal microbiota of piglets fed with wheat bran variants as characterised by 16S rRNA next-generation amplicon sequencing. 27032029 11 70 theme feeding 1867:1873 arg1 strategies 1875:1884 the various feeding strategies 1855:1884 the various feeding strategies applied 1855:1892 Although statistical taxonomical evaluation, following p-value correction, did not reveal pronounced differences in abundance related to bran modification, alpha and beta diversity analysis showed an influence regarding the various feeding strategies applied. 27032029 0 71 theme intestinal 4:13 arg1 microbiota 15:24 The intestinal microbiota 0:24 The intestinal microbiota of piglets 0:35 The intestinal microbiota of piglets fed with wheat bran variants as characterised by 16S rRNA next-generation amplicon sequencing. 27032029 8 72 theme alpha 1028:1032 arg1 parameters 1014:1023 The parameters 1010:1023 The parameters of alpha and beta diversity analysis 1010:1060 The parameters of alpha and beta diversity analysis showed significant differences (p < 0.01) between the colon and the other two gut segments. 27032029 7 73 attach predominant 901:911 arg2 Firmicutes 880:889 Firmicutes 880:889 Firmicutes 880:889 While Firmicutes were most predominant in all three gut segments, Bacteroidetes were additionally found in the colon at high abundance. 27032029 7 73 attach predominant 901:911 arg1 segments 930:937 all three gut segments 916:937 all three gut segments 916:937 While Firmicutes were most predominant in all three gut segments, Bacteroidetes were additionally found in the colon at high abundance. 27032029 3 74 theme Wheat 409:413 arg1 bran 415:418 Wheat bran 409:418 Wheat bran 409:418 Wheat bran was either included in its native form or modified by fermentation and extrusion before added at 150 g/kg to a basal diet for 48 piglets (12 animals per treatment). 27032029 9 75 theme cellulolytic 1292:1303 arg1 properties 1305:1314 cellulolytic properties 1292:1314 cellulolytic properties 1292:1314 Specialised bacterial groups like Prevotella and Ruminococcaceae were among the most predominant ones found in the colon, as they possess cellulolytic properties to degrade (at least partially) non-starch polysaccharides, while their abundance was negligible in the jejunum and the ileum. 27032029 8 76 theme beta 1038:1041 arg1 parameters 1014:1023 The parameters 1010:1023 The parameters of alpha and beta diversity analysis 1010:1060 The parameters of alpha and beta diversity analysis showed significant differences (p < 0.01) between the colon and the other two gut segments. 27032029 11 77 theme various 1859:1865 arg1 strategies 1875:1884 the various feeding strategies 1855:1884 the various feeding strategies applied 1855:1892 Although statistical taxonomical evaluation, following p-value correction, did not reveal pronounced differences in abundance related to bran modification, alpha and beta diversity analysis showed an influence regarding the various feeding strategies applied. 27032029 1 78 theme modified 218:225 arg1 bran 233:236 modified wheat bran 218:236 modified wheat bran 218:236 The intestinal microbiota of piglets fed with a Control diet low in dietary fibre and modified wheat bran variants as an additional source of insoluble dietary fibre was characterised. 27032029 2 79 theme gut 381:383 arg1 segments 385:392 three different gut segments 365:392 three different gut segments 365:392 In this context, variances in the microbiota of three different gut segments were assessed. 27032029 0 80 theme wheat 46:50 arg1 bran 52:55 wheat bran 46:55 wheat bran variants 46:64 The intestinal microbiota of piglets fed with wheat bran variants as characterised by 16S rRNA next-generation amplicon sequencing. 27032029 1 81 theme fibre 292:296 arg1 source 264:269 an additional source 250:269 an additional source of insoluble dietary fibre 250:296 The intestinal microbiota of piglets fed with a Control diet low in dietary fibre and modified wheat bran variants as an additional source of insoluble dietary fibre was characterised. 27032029 8 82 theme significant 1069:1079 arg1 p < 0.01 1094:1101 p < 0.01 1094:1101 p < 0.01 1094:1101 The parameters of alpha and beta diversity analysis showed significant differences (p < 0.01) between the colon and the other two gut segments. 27032029 8 82 theme significant 1069:1079 arg1 differences 1081:1091 significant differences 1069:1091 significant differences (p < 0.01) between the colon and the other two gut segments 1069:1151 The parameters of alpha and beta diversity analysis showed significant differences (p < 0.01) between the colon and the other two gut segments. 27032029 6 83 theme obtained 783:790 arg1 results 792:798 The obtained results 779:798 The obtained results 779:798 The obtained results revealed distinct location-specific differences in microbial composition. 27032029 9 84 from ileum 1436:1440 arg1 negligible 1402:1411 negligible 1402:1411 negligible 1402:1411 Specialised bacterial groups like Prevotella and Ruminococcaceae were among the most predominant ones found in the colon, as they possess cellulolytic properties to degrade (at least partially) non-starch polysaccharides, while their abundance was negligible in the jejunum and the ileum. 27032029 11 85 theme diversity 1806:1814 arg1 analysis 1816:1823 alpha and beta diversity analysis 1791:1823 alpha and beta diversity analysis 1791:1823 Although statistical taxonomical evaluation, following p-value correction, did not reveal pronounced differences in abundance related to bran modification, alpha and beta diversity analysis showed an influence regarding the various feeding strategies applied. 27032029 11 86 theme statistical 1644:1654 arg1 evaluation 1668:1677 statistical taxonomical evaluation 1644:1677 statistical taxonomical evaluation 1644:1677 Although statistical taxonomical evaluation, following p-value correction, did not reveal pronounced differences in abundance related to bran modification, alpha and beta diversity analysis showed an influence regarding the various feeding strategies applied. 27032029 5 87 theme subsequent 732:741 arg1 sequencing 743:752 subsequent sequencing 732:752 subsequent sequencing with the Illumina MiSeq 732:776 Samples were prepared accordingly for subsequent sequencing with the Illumina MiSeq. 27032029 4 88 from jejunum 639:645 arg1 ascendens 683:691 the colon ascendens 673:691 the colon ascendens 673:691 Total DNA was extracted from digesta samples from the jejunum, the end of the ileum and the colon ascendens. 27032029 4 88 from jejunum 639:645 arg1 samples 622:628 digesta samples 614:628 digesta samples from the jejunum 614:645 Total DNA was extracted from digesta samples from the jejunum, the end of the ileum and the colon ascendens. 27032029 4 88 from jejunum 639:645 arg1 end 652:654 the end 648:654 the end of the ileum 648:667 Total DNA was extracted from digesta samples from the jejunum, the end of the ileum and the colon ascendens. 27032029 1 89 theme wheat 227:231 arg1 bran 233:236 modified wheat bran 218:236 modified wheat bran 218:236 The intestinal microbiota of piglets fed with a Control diet low in dietary fibre and modified wheat bran variants as an additional source of insoluble dietary fibre was characterised. 27936604 7 0 theme ± 1456:1456 arg1 mM 1460:1461 2 ± 1 mM 1454:1461 2 ± 1 mM (Vmax, 400 ± 100 μM/min) 1454:1486 The enzyme cleaves the 2-3 linkage faster than the 2-6, and a KM of 2 ± 1 mM (Vmax, 400 ± 100 μM/min) was obtained for the 6'-sialyllactose substrate. 27936604 10 1 theme acid 1984:1987 arg1 linkages 1989:1996 3' and 6' sialic acid linkages 1967:1996 3' and 6' sialic acid linkages 1967:1996 Nanogel electrophoresis is an inexpensive, rapid, and simple alternative to current technologies used to distinguish the composition of 3' and 6' sialic acid linkages. 27936604 0 2 with Constants 44:52 arg1 Electrophoresis 94:108 Nanogel Capillary Electrophoresis 76:108 Nanogel Capillary Electrophoresis 76:108 Microscale Measurements of Michaelis-Menten Constants of Neuraminidase with Nanogel Capillary Electrophoresis for the Determination of the Sialic Acid Linkage. 27936604 3 3 theme different 504:512 arg1 substrates 514:523 different substrates 504:523 different substrates 504:523 This enables rapid quantification of Michaelis-Menten constants (KM) for different substrates and ultimately provides a means to quantify the linkage (i.e., 2-3 versus 2-6) of sialic acids. 27936604 8 4 theme KM 1617:1618 arg1 value 1620:1624 a KM value 1615:1624 a KM value of 3 ± 2 mM (Vmax, 900 ± 300 μM/min) for 3'-sialyllactose 1615:1682 An alternative neuraminidase selective for 2-3 sialic acid linkages generated a KM value of 3 ± 2 mM (Vmax, 900 ± 300 μM/min) for 3'-sialyllactose. 27936604 6 5 theme benchtop 1367:1374 arg1 analyses 1376:1383 benchtop analyses 1367:1383 benchtop analyses 1367:1383 A KM value of 3.3 ± 0.8 mM (Vmax, 2100 ± 200 μM/min) was obtained for 3'-sialyllactose labeled with 2-aminobenzoic acid using neuraminidase from Clostridium perfringens that cleaves sialic acid monomers with an α2-3,6,8,9 linkage, which is similar to values reported in the literature that required benchtop analyses. 27936604 6 6 theme α2-3,6,8,9 1279:1288 arg1 similar 1308:1314 similar 1308:1314 similar 1308:1314 A KM value of 3.3 ± 0.8 mM (Vmax, 2100 ± 200 μM/min) was obtained for 3'-sialyllactose labeled with 2-aminobenzoic acid using neuraminidase from Clostridium perfringens that cleaves sialic acid monomers with an α2-3,6,8,9 linkage, which is similar to values reported in the literature that required benchtop analyses. 27936604 6 6 theme α2-3,6,8,9 1279:1288 arg1 linkage 1290:1296 an α2-3,6,8,9 linkage 1276:1296 an α2-3,6,8,9 linkage 1276:1296 A KM value of 3.3 ± 0.8 mM (Vmax, 2100 ± 200 μM/min) was obtained for 3'-sialyllactose labeled with 2-aminobenzoic acid using neuraminidase from Clostridium perfringens that cleaves sialic acid monomers with an α2-3,6,8,9 linkage, which is similar to values reported in the literature that required benchtop analyses. 27936604 6 7 theme 0.8 1088:1090 arg1 ± 1086:1086 ± 1086:1086 ± 1086:1086 A KM value of 3.3 ± 0.8 mM (Vmax, 2100 ± 200 μM/min) was obtained for 3'-sialyllactose labeled with 2-aminobenzoic acid using neuraminidase from Clostridium perfringens that cleaves sialic acid monomers with an α2-3,6,8,9 linkage, which is similar to values reported in the literature that required benchtop analyses. 27936604 7 8 dep mM 1460:1461 arg1 μM/min 1480:1485 400 ± 100 μM/min 1470:1485 400 ± 100 μM/min 1470:1485 The enzyme cleaves the 2-3 linkage faster than the 2-6, and a KM of 2 ± 1 mM (Vmax, 400 ± 100 μM/min) was obtained for the 6'-sialyllactose substrate. 27936604 7 8 dep mM 1460:1461 arg1 Vmax 1464:1467 Vmax 1464:1467 Vmax 1464:1467 The enzyme cleaves the 2-3 linkage faster than the 2-6, and a KM of 2 ± 1 mM (Vmax, 400 ± 100 μM/min) was obtained for the 6'-sialyllactose substrate. 27936604 4 9 theme sialic 781:786 arg1 linkages 793:800 sialic acid linkages 781:800 sialic acid linkages 781:800 The fixed zone of enzyme is inexpensive and easily positioned in the capillary to support electrophoresis mediated microanalysis using neuraminidase to analyze sialic acid linkages. 27936604 9 10 theme sialyllactose 1762:1774 arg1 mixture 1739:1745 a mixture 1737:1745 a mixture of 2-3 and 2-6 sialyllactose as well as 2-3 and 2-6 sialylated triantennary glycan 1737:1828 With a knowledge of Vmax, the method was applied to a mixture of 2-3 and 2-6 sialyllactose as well as 2-3 and 2-6 sialylated triantennary glycan. 27936604 9 10 theme sialyllactose 1762:1774 arg1 glycan 1823:1828 2-3 and 2-6 sialylated triantennary glycan 1787:1828 a mixture of 2-3 and 2-6 sialyllactose as well as 2-3 and 2-6 sialylated triantennary glycan 1737:1828 With a knowledge of Vmax, the method was applied to a mixture of 2-3 and 2-6 sialyllactose as well as 2-3 and 2-6 sialylated triantennary glycan. 27936604 5 11 theme in-capillary 1031:1042 arg1 mixing 1060:1065 in-capillary electrophoretic mixing 1031:1065 in-capillary electrophoretic mixing 1031:1065 To circumvent the limitations of diffusion during static incubation, the incubation period is reproducibly achieved by varying the number of forward and reverse passes the substrate makes through the stationary fixed zone using in-capillary electrophoretic mixing. 27936604 5 12 theme passes 964:969 arg1 number 934:939 the number 930:939 the number of forward and reverse passes the substrate makes through the stationary fixed zone using in-capillary electrophoretic mixing 930:1065 To circumvent the limitations of diffusion during static incubation, the incubation period is reproducibly achieved by varying the number of forward and reverse passes the substrate makes through the stationary fixed zone using in-capillary electrophoretic mixing. 27936604 5 13 theme reverse 956:962 arg1 passes 964:969 forward and reverse passes 944:969 forward and reverse passes the substrate makes through the stationary fixed zone using in-capillary electrophoretic mixing 944:1065 To circumvent the limitations of diffusion during static incubation, the incubation period is reproducibly achieved by varying the number of forward and reverse passes the substrate makes through the stationary fixed zone using in-capillary electrophoretic mixing. 27936604 1 14 theme fixed 288:292 arg1 zone 294:297 a fixed zone 286:297 a fixed zone of enzyme 286:307 Phospholipid nanogels enhance the stability and performance of the exoglycosidase enzyme neuraminidase and are used to create a fixed zone of enzyme within a capillary. 27936604 6 15 theme mM 1092:1093 arg1 value 1073:1077 A KM value 1068:1077 A KM value of 3.3 ± 0.8 mM (Vmax, 2100 ± 200 μM/min) 1068:1119 A KM value of 3.3 ± 0.8 mM (Vmax, 2100 ± 200 μM/min) was obtained for 3'-sialyllactose labeled with 2-aminobenzoic acid using neuraminidase from Clostridium perfringens that cleaves sialic acid monomers with an α2-3,6,8,9 linkage, which is similar to values reported in the literature that required benchtop analyses. 27936604 10 16 theme sialic 1977:1982 arg1 linkages 1989:1996 3' and 6' sialic acid linkages 1967:1996 3' and 6' sialic acid linkages 1967:1996 Nanogel electrophoresis is an inexpensive, rapid, and simple alternative to current technologies used to distinguish the composition of 3' and 6' sialic acid linkages. 27936604 8 17 theme 2-3 1580:1582 arg1 linkages 1596:1603 2-3 sialic acid linkages 1580:1603 2-3 sialic acid linkages 1580:1603 An alternative neuraminidase selective for 2-3 sialic acid linkages generated a KM value of 3 ± 2 mM (Vmax, 900 ± 300 μM/min) for 3'-sialyllactose. 27936604 10 18 theme rapid 1874:1878 arg1 electrophoresis 1839:1853 Nanogel electrophoresis 1831:1853 Nanogel electrophoresis 1831:1853 Nanogel electrophoresis is an inexpensive, rapid, and simple alternative to current technologies used to distinguish the composition of 3' and 6' sialic acid linkages. 27936604 10 18 theme rapid 1874:1878 arg1 alternative 1892:1902 an inexpensive, rapid, and simple alternative 1858:1902 an inexpensive, rapid, and simple alternative to current technologies used to distinguish the composition of 3' and 6' sialic acid linkages 1858:1996 Nanogel electrophoresis is an inexpensive, rapid, and simple alternative to current technologies used to distinguish the composition of 3' and 6' sialic acid linkages. 27936604 5 19 theme diffusion 836:844 arg1 limitations 821:831 the limitations 817:831 the limitations of diffusion 817:844 To circumvent the limitations of diffusion during static incubation, the incubation period is reproducibly achieved by varying the number of forward and reverse passes the substrate makes through the stationary fixed zone using in-capillary electrophoretic mixing. 27936604 1 20 theme exoglycosidase 227:240 arg1 neuraminidase 249:261 the exoglycosidase enzyme neuraminidase 223:261 the exoglycosidase enzyme neuraminidase 223:261 Phospholipid nanogels enhance the stability and performance of the exoglycosidase enzyme neuraminidase and are used to create a fixed zone of enzyme within a capillary. 27936604 8 21 theme ± 1631:1631 arg1 mM 1635:1636 3 ± 2 mM 1629:1636 3 ± 2 mM (Vmax, 900 ± 300 μM/min) 1629:1661 An alternative neuraminidase selective for 2-3 sialic acid linkages generated a KM value of 3 ± 2 mM (Vmax, 900 ± 300 μM/min) for 3'-sialyllactose. 27936604 3 22 dep i.e. 582:585 arg1 2-3 588:590 2-3 588:590 2-3 588:590 This enables rapid quantification of Michaelis-Menten constants (KM) for different substrates and ultimately provides a means to quantify the linkage (i.e., 2-3 versus 2-6) of sialic acids. 27936604 3 22 dep i.e. 582:585 arg1 2-6 599:601 2-6 599:601 2-6 599:601 This enables rapid quantification of Michaelis-Menten constants (KM) for different substrates and ultimately provides a means to quantify the linkage (i.e., 2-3 versus 2-6) of sialic acids. 27936604 6 23 theme acid 1257:1260 arg1 monomers 1262:1269 sialic acid monomers 1250:1269 sialic acid monomers 1250:1269 A KM value of 3.3 ± 0.8 mM (Vmax, 2100 ± 200 μM/min) was obtained for 3'-sialyllactose labeled with 2-aminobenzoic acid using neuraminidase from Clostridium perfringens that cleaves sialic acid monomers with an α2-3,6,8,9 linkage, which is similar to values reported in the literature that required benchtop analyses. 27936604 7 24 theme faster 1421:1426 arg1 linkage 1413:1419 the 2-3 linkage 1405:1419 the 2-3 linkage faster than the 2-6 1405:1439 The enzyme cleaves the 2-3 linkage faster than the 2-6, and a KM of 2 ± 1 mM (Vmax, 400 ± 100 μM/min) was obtained for the 6'-sialyllactose substrate. 27936604 10 25 theme 6 1974:1974 arg1 linkages 1989:1996 3' and 6' sialic acid linkages 1967:1996 3' and 6' sialic acid linkages 1967:1996 Nanogel electrophoresis is an inexpensive, rapid, and simple alternative to current technologies used to distinguish the composition of 3' and 6' sialic acid linkages. 27936604 3 26 theme rapid 444:448 arg1 quantification 450:463 rapid quantification 444:463 rapid quantification of Michaelis-Menten constants (KM) for different substrates 444:523 This enables rapid quantification of Michaelis-Menten constants (KM) for different substrates and ultimately provides a means to quantify the linkage (i.e., 2-3 versus 2-6) of sialic acids. 27936604 6 27 theme sialic 1250:1255 arg1 monomers 1262:1269 sialic acid monomers 1250:1269 sialic acid monomers 1250:1269 A KM value of 3.3 ± 0.8 mM (Vmax, 2100 ± 200 μM/min) was obtained for 3'-sialyllactose labeled with 2-aminobenzoic acid using neuraminidase from Clostridium perfringens that cleaves sialic acid monomers with an α2-3,6,8,9 linkage, which is similar to values reported in the literature that required benchtop analyses. 27936604 8 28 dep mM 1635:1636 arg1 μM/min 1655:1660 900 ± 300 μM/min 1645:1660 900 ± 300 μM/min 1645:1660 An alternative neuraminidase selective for 2-3 sialic acid linkages generated a KM value of 3 ± 2 mM (Vmax, 900 ± 300 μM/min) for 3'-sialyllactose. 27936604 8 28 dep mM 1635:1636 arg1 Vmax 1639:1642 Vmax 1639:1642 Vmax 1639:1642 An alternative neuraminidase selective for 2-3 sialic acid linkages generated a KM value of 3 ± 2 mM (Vmax, 900 ± 300 μM/min) for 3'-sialyllactose. 27936604 4 29 theme electrophoresis 711:725 arg1 microanalysis 736:748 electrophoresis mediated microanalysis 711:748 electrophoresis mediated microanalysis using neuraminidase to analyze sialic acid linkages 711:800 The fixed zone of enzyme is inexpensive and easily positioned in the capillary to support electrophoresis mediated microanalysis using neuraminidase to analyze sialic acid linkages. 27936604 8 30 theme mM 1635:1636 arg1 value 1620:1624 a KM value 1615:1624 a KM value of 3 ± 2 mM (Vmax, 900 ± 300 μM/min) for 3'-sialyllactose 1615:1682 An alternative neuraminidase selective for 2-3 sialic acid linkages generated a KM value of 3 ± 2 mM (Vmax, 900 ± 300 μM/min) for 3'-sialyllactose. 27936604 0 31 theme Microscale 0:9 arg1 Measurements 11:22 Microscale Measurements 0:22 Microscale Measurements of Michaelis-Menten Constants of Neuraminidase with Nanogel Capillary Electrophoresis for the Determination of the Sialic Acid Linkage. 0:158 Microscale Measurements of Michaelis-Menten Constants of Neuraminidase with Nanogel Capillary Electrophoresis for the Determination of the Sialic Acid Linkage. 27936604 7 32 theme mM 1460:1461 arg1 KM 1448:1449 a KM 1446:1449 a KM of 2 ± 1 mM (Vmax, 400 ± 100 μM/min) 1446:1486 The enzyme cleaves the 2-3 linkage faster than the 2-6, and a KM of 2 ± 1 mM (Vmax, 400 ± 100 μM/min) was obtained for the 6'-sialyllactose substrate. 27936604 5 33 theme forward 944:950 arg1 passes 964:969 forward and reverse passes 944:969 forward and reverse passes the substrate makes through the stationary fixed zone using in-capillary electrophoretic mixing 944:1065 To circumvent the limitations of diffusion during static incubation, the incubation period is reproducibly achieved by varying the number of forward and reverse passes the substrate makes through the stationary fixed zone using in-capillary electrophoretic mixing. 27936604 4 34 theme enzyme 639:644 arg1 zone 631:634 The fixed zone 621:634 The fixed zone of enzyme 621:644 The fixed zone of enzyme is inexpensive and easily positioned in the capillary to support electrophoresis mediated microanalysis using neuraminidase to analyze sialic acid linkages. 27936604 0 35 theme Michaelis-Menten 27:42 arg1 Constants 44:52 Michaelis-Menten Constants 27:52 Michaelis-Menten Constants of Neuraminidase with Nanogel Capillary Electrophoresis 27:108 Microscale Measurements of Michaelis-Menten Constants of Neuraminidase with Nanogel Capillary Electrophoresis for the Determination of the Sialic Acid Linkage. 27936604 1 36 theme enzyme 302:307 arg1 zone 294:297 a fixed zone 286:297 a fixed zone of enzyme 286:307 Phospholipid nanogels enhance the stability and performance of the exoglycosidase enzyme neuraminidase and are used to create a fixed zone of enzyme within a capillary. 27936604 0 37 theme Acid 146:149 arg1 Linkage 151:157 the Sialic Acid Linkage 135:157 the Sialic Acid Linkage 135:157 Microscale Measurements of Michaelis-Menten Constants of Neuraminidase with Nanogel Capillary Electrophoresis for the Determination of the Sialic Acid Linkage. 27936604 6 38 from perfringens 1225:1235 arg1 neuraminidase 1194:1206 neuraminidase 1194:1206 neuraminidase from Clostridium perfringens that cleaves sialic acid monomers with an α2-3,6,8,9 linkage, which is similar to values reported in the literature that required benchtop analyses 1194:1383 A KM value of 3.3 ± 0.8 mM (Vmax, 2100 ± 200 μM/min) was obtained for 3'-sialyllactose labeled with 2-aminobenzoic acid using neuraminidase from Clostridium perfringens that cleaves sialic acid monomers with an α2-3,6,8,9 linkage, which is similar to values reported in the literature that required benchtop analyses. 27936604 3 39 theme Michaelis-Menten 468:483 arg1 KM 496:497 KM 496:497 KM 496:497 This enables rapid quantification of Michaelis-Menten constants (KM) for different substrates and ultimately provides a means to quantify the linkage (i.e., 2-3 versus 2-6) of sialic acids. 27936604 3 39 theme Michaelis-Menten 468:483 arg1 constants 485:493 Michaelis-Menten constants 468:493 Michaelis-Menten constants (KM) for different substrates 468:523 This enables rapid quantification of Michaelis-Menten constants (KM) for different substrates and ultimately provides a means to quantify the linkage (i.e., 2-3 versus 2-6) of sialic acids. 27936604 7 40 theme 2-3 1409:1411 arg1 linkage 1413:1419 the 2-3 linkage 1405:1419 the 2-3 linkage faster than the 2-6 1405:1439 The enzyme cleaves the 2-3 linkage faster than the 2-6, and a KM of 2 ± 1 mM (Vmax, 400 ± 100 μM/min) was obtained for the 6'-sialyllactose substrate. 27936604 0 41 theme Sialic 139:144 arg1 Linkage 151:157 the Sialic Acid Linkage 135:157 the Sialic Acid Linkage 135:157 Microscale Measurements of Michaelis-Menten Constants of Neuraminidase with Nanogel Capillary Electrophoresis for the Determination of the Sialic Acid Linkage. 27936604 7 42 theme ± 1474:1474 arg1 μM/min 1480:1485 400 ± 100 μM/min 1470:1485 400 ± 100 μM/min 1470:1485 The enzyme cleaves the 2-3 linkage faster than the 2-6, and a KM of 2 ± 1 mM (Vmax, 400 ± 100 μM/min) was obtained for the 6'-sialyllactose substrate. 27936604 7 42 theme ± 1474:1474 arg1 Vmax 1464:1467 Vmax 1464:1467 Vmax 1464:1467 The enzyme cleaves the 2-3 linkage faster than the 2-6, and a KM of 2 ± 1 mM (Vmax, 400 ± 100 μM/min) was obtained for the 6'-sialyllactose substrate. 27936604 4 43 theme mediated 727:734 arg1 microanalysis 736:748 electrophoresis mediated microanalysis 711:748 electrophoresis mediated microanalysis using neuraminidase to analyze sialic acid linkages 711:800 The fixed zone of enzyme is inexpensive and easily positioned in the capillary to support electrophoresis mediated microanalysis using neuraminidase to analyze sialic acid linkages. 27936604 8 44 theme ± 1649:1649 arg1 μM/min 1655:1660 900 ± 300 μM/min 1645:1660 900 ± 300 μM/min 1645:1660 An alternative neuraminidase selective for 2-3 sialic acid linkages generated a KM value of 3 ± 2 mM (Vmax, 900 ± 300 μM/min) for 3'-sialyllactose. 27936604 8 44 theme ± 1649:1649 arg1 Vmax 1639:1642 Vmax 1639:1642 Vmax 1639:1642 An alternative neuraminidase selective for 2-3 sialic acid linkages generated a KM value of 3 ± 2 mM (Vmax, 900 ± 300 μM/min) for 3'-sialyllactose. 27936604 3 45 theme constants 485:493 arg1 quantification 450:463 rapid quantification 444:463 rapid quantification of Michaelis-Menten constants (KM) for different substrates 444:523 This enables rapid quantification of Michaelis-Menten constants (KM) for different substrates and ultimately provides a means to quantify the linkage (i.e., 2-3 versus 2-6) of sialic acids. 27936604 6 46 theme Clostridium 1213:1223 arg1 perfringens 1225:1235 Clostridium perfringens 1213:1235 Clostridium perfringens 1213:1235 A KM value of 3.3 ± 0.8 mM (Vmax, 2100 ± 200 μM/min) was obtained for 3'-sialyllactose labeled with 2-aminobenzoic acid using neuraminidase from Clostridium perfringens that cleaves sialic acid monomers with an α2-3,6,8,9 linkage, which is similar to values reported in the literature that required benchtop analyses. 27936604 4 47 theme fixed 625:629 arg1 zone 631:634 The fixed zone 621:634 The fixed zone of enzyme 621:644 The fixed zone of enzyme is inexpensive and easily positioned in the capillary to support electrophoresis mediated microanalysis using neuraminidase to analyze sialic acid linkages. 27936604 6 48 dep mM 1092:1093 arg1 μM/min 1113:1118 2100 ± 200 μM/min 1102:1118 2100 ± 200 μM/min 1102:1118 A KM value of 3.3 ± 0.8 mM (Vmax, 2100 ± 200 μM/min) was obtained for 3'-sialyllactose labeled with 2-aminobenzoic acid using neuraminidase from Clostridium perfringens that cleaves sialic acid monomers with an α2-3,6,8,9 linkage, which is similar to values reported in the literature that required benchtop analyses. 27936604 6 48 dep mM 1092:1093 arg1 Vmax 1096:1099 Vmax 1096:1099 Vmax 1096:1099 A KM value of 3.3 ± 0.8 mM (Vmax, 2100 ± 200 μM/min) was obtained for 3'-sialyllactose labeled with 2-aminobenzoic acid using neuraminidase from Clostridium perfringens that cleaves sialic acid monomers with an α2-3,6,8,9 linkage, which is similar to values reported in the literature that required benchtop analyses. 27936604 5 49 theme incubation 876:885 arg1 period 887:892 the incubation period 872:892 the incubation period 872:892 To circumvent the limitations of diffusion during static incubation, the incubation period is reproducibly achieved by varying the number of forward and reverse passes the substrate makes through the stationary fixed zone using in-capillary electrophoretic mixing. 27936604 1 50 theme enzyme 242:247 arg1 neuraminidase 249:261 the exoglycosidase enzyme neuraminidase 223:261 the exoglycosidase enzyme neuraminidase 223:261 Phospholipid nanogels enhance the stability and performance of the exoglycosidase enzyme neuraminidase and are used to create a fixed zone of enzyme within a capillary. 27936604 0 51 theme Constants 44:52 arg1 Measurements 11:22 Microscale Measurements 0:22 Microscale Measurements of Michaelis-Menten Constants of Neuraminidase with Nanogel Capillary Electrophoresis for the Determination of the Sialic Acid Linkage. 0:158 Microscale Measurements of Michaelis-Menten Constants of Neuraminidase with Nanogel Capillary Electrophoresis for the Determination of the Sialic Acid Linkage. 27936604 0 52 theme Linkage 151:157 arg1 Determination 118:130 the Determination 114:130 the Determination of the Sialic Acid Linkage 114:157 Microscale Measurements of Michaelis-Menten Constants of Neuraminidase with Nanogel Capillary Electrophoresis for the Determination of the Sialic Acid Linkage. 27936604 3 53 theme acids 614:618 arg1 linkage 573:579 the linkage 569:579 the linkage (i.e., 2-3 versus 2-6) of sialic acids 569:618 This enables rapid quantification of Michaelis-Menten constants (KM) for different substrates and ultimately provides a means to quantify the linkage (i.e., 2-3 versus 2-6) of sialic acids. 27936604 9 54 theme Vmax 1705:1708 arg1 knowledge 1692:1700 a knowledge 1690:1700 a knowledge of Vmax 1690:1708 With a knowledge of Vmax, the method was applied to a mixture of 2-3 and 2-6 sialyllactose as well as 2-3 and 2-6 sialylated triantennary glycan. 27936604 1 55 theme neuraminidase 249:261 arg1 performance 208:218 performance 208:218 performance 208:218 Phospholipid nanogels enhance the stability and performance of the exoglycosidase enzyme neuraminidase and are used to create a fixed zone of enzyme within a capillary. 27936604 1 55 theme neuraminidase 249:261 arg1 stability 194:202 stability 194:202 stability 194:202 Phospholipid nanogels enhance the stability and performance of the exoglycosidase enzyme neuraminidase and are used to create a fixed zone of enzyme within a capillary. 27936604 10 56 theme inexpensive 1861:1871 arg1 electrophoresis 1839:1853 Nanogel electrophoresis 1831:1853 Nanogel electrophoresis 1831:1853 Nanogel electrophoresis is an inexpensive, rapid, and simple alternative to current technologies used to distinguish the composition of 3' and 6' sialic acid linkages. 27936604 10 56 theme inexpensive 1861:1871 arg1 alternative 1892:1902 an inexpensive, rapid, and simple alternative 1858:1902 an inexpensive, rapid, and simple alternative to current technologies used to distinguish the composition of 3' and 6' sialic acid linkages 1858:1996 Nanogel electrophoresis is an inexpensive, rapid, and simple alternative to current technologies used to distinguish the composition of 3' and 6' sialic acid linkages. 27936604 10 57 theme Nanogel 1831:1837 arg1 electrophoresis 1839:1853 Nanogel electrophoresis 1831:1853 Nanogel electrophoresis 1831:1853 Nanogel electrophoresis is an inexpensive, rapid, and simple alternative to current technologies used to distinguish the composition of 3' and 6' sialic acid linkages. 27936604 10 57 theme Nanogel 1831:1837 arg1 alternative 1892:1902 an inexpensive, rapid, and simple alternative 1858:1902 an inexpensive, rapid, and simple alternative to current technologies used to distinguish the composition of 3' and 6' sialic acid linkages 1858:1996 Nanogel electrophoresis is an inexpensive, rapid, and simple alternative to current technologies used to distinguish the composition of 3' and 6' sialic acid linkages. 27936604 1 58 dep stability 194:202 arg1 the 190:192 the 190:192 the 190:192 Phospholipid nanogels enhance the stability and performance of the exoglycosidase enzyme neuraminidase and are used to create a fixed zone of enzyme within a capillary. 27936604 0 59 theme Neuraminidase 57:69 arg1 Constants 44:52 Michaelis-Menten Constants 27:52 Michaelis-Menten Constants of Neuraminidase with Nanogel Capillary Electrophoresis 27:108 Microscale Measurements of Michaelis-Menten Constants of Neuraminidase with Nanogel Capillary Electrophoresis for the Determination of the Sialic Acid Linkage. 27936604 5 60 theme electrophoretic 1044:1058 arg1 mixing 1060:1065 in-capillary electrophoretic mixing 1031:1065 in-capillary electrophoretic mixing 1031:1065 To circumvent the limitations of diffusion during static incubation, the incubation period is reproducibly achieved by varying the number of forward and reverse passes the substrate makes through the stationary fixed zone using in-capillary electrophoretic mixing. 27936604 9 61 theme triantennary 1810:1821 arg1 glycan 1823:1828 2-3 and 2-6 sialylated triantennary glycan 1787:1828 a mixture of 2-3 and 2-6 sialyllactose as well as 2-3 and 2-6 sialylated triantennary glycan 1737:1828 With a knowledge of Vmax, the method was applied to a mixture of 2-3 and 2-6 sialyllactose as well as 2-3 and 2-6 sialylated triantennary glycan. 27936604 6 62 theme 2-aminobenzoic 1168:1181 arg1 acid 1183:1186 2-aminobenzoic acid 1168:1186 2-aminobenzoic acid using neuraminidase from Clostridium perfringens that cleaves sialic acid monomers with an α2-3,6,8,9 linkage, which is similar to values reported in the literature that required benchtop analyses 1168:1383 A KM value of 3.3 ± 0.8 mM (Vmax, 2100 ± 200 μM/min) was obtained for 3'-sialyllactose labeled with 2-aminobenzoic acid using neuraminidase from Clostridium perfringens that cleaves sialic acid monomers with an α2-3,6,8,9 linkage, which is similar to values reported in the literature that required benchtop analyses. 27936604 8 63 theme selective 1566:1574 arg1 neuraminidase 1552:1564 An alternative neuraminidase 1537:1564 An alternative neuraminidase selective for 2-3 sialic acid linkages 1537:1603 An alternative neuraminidase selective for 2-3 sialic acid linkages generated a KM value of 3 ± 2 mM (Vmax, 900 ± 300 μM/min) for 3'-sialyllactose. 27936604 1 64 used used 271:274 arg2 nanogels 173:180 Phospholipid nanogels 160:180 Phospholipid nanogels 160:180 Phospholipid nanogels enhance the stability and performance of the exoglycosidase enzyme neuraminidase and are used to create a fixed zone of enzyme within a capillary. 27936604 4 65 theme acid 788:791 arg1 linkages 793:800 sialic acid linkages 781:800 sialic acid linkages 781:800 The fixed zone of enzyme is inexpensive and easily positioned in the capillary to support electrophoresis mediated microanalysis using neuraminidase to analyze sialic acid linkages. 27936604 10 66 theme linkages 1989:1996 arg1 composition 1952:1962 the composition 1948:1962 the composition of 3' and 6' sialic acid linkages 1948:1996 Nanogel electrophoresis is an inexpensive, rapid, and simple alternative to current technologies used to distinguish the composition of 3' and 6' sialic acid linkages. 27936604 5 67 dep passes 964:969 arg1 makes 985:989 makes 985:989 makes through the stationary fixed zone using in-capillary electrophoretic mixing 985:1065 To circumvent the limitations of diffusion during static incubation, the incubation period is reproducibly achieved by varying the number of forward and reverse passes the substrate makes through the stationary fixed zone using in-capillary electrophoretic mixing. 27936604 8 68 theme acid 1591:1594 arg1 linkages 1596:1603 2-3 sialic acid linkages 1580:1603 2-3 sialic acid linkages 1580:1603 An alternative neuraminidase selective for 2-3 sialic acid linkages generated a KM value of 3 ± 2 mM (Vmax, 900 ± 300 μM/min) for 3'-sialyllactose. 27936604 7 69 theme 6'-sialyllactose 1509:1524 arg1 substrate 1526:1534 the 6'-sialyllactose substrate 1505:1534 the 6'-sialyllactose substrate 1505:1534 The enzyme cleaves the 2-3 linkage faster than the 2-6, and a KM of 2 ± 1 mM (Vmax, 400 ± 100 μM/min) was obtained for the 6'-sialyllactose substrate. 27936604 9 70 gly sialylated 1799:1808 arg1 glycan 1823:1828 2-3 and 2-6 sialylated triantennary glycan 1787:1828 a mixture of 2-3 and 2-6 sialyllactose as well as 2-3 and 2-6 sialylated triantennary glycan 1737:1828 With a knowledge of Vmax, the method was applied to a mixture of 2-3 and 2-6 sialyllactose as well as 2-3 and 2-6 sialylated triantennary glycan. 27936604 3 71 theme sialic 607:612 arg1 acids 614:618 sialic acids 607:618 sialic acids 607:618 This enables rapid quantification of Michaelis-Menten constants (KM) for different substrates and ultimately provides a means to quantify the linkage (i.e., 2-3 versus 2-6) of sialic acids. 27936604 9 72 theme sialylated 1799:1808 arg1 glycan 1823:1828 2-3 and 2-6 sialylated triantennary glycan 1787:1828 a mixture of 2-3 and 2-6 sialyllactose as well as 2-3 and 2-6 sialylated triantennary glycan 1737:1828 With a knowledge of Vmax, the method was applied to a mixture of 2-3 and 2-6 sialyllactose as well as 2-3 and 2-6 sialylated triantennary glycan. 27936604 10 73 theme current 1907:1913 arg1 technologies 1915:1926 current technologies 1907:1926 current technologies used to distinguish the composition of 3' and 6' sialic acid linkages 1907:1996 Nanogel electrophoresis is an inexpensive, rapid, and simple alternative to current technologies used to distinguish the composition of 3' and 6' sialic acid linkages. 27936604 0 74 theme Capillary 84:92 arg1 Electrophoresis 94:108 Nanogel Capillary Electrophoresis 76:108 Nanogel Capillary Electrophoresis 76:108 Microscale Measurements of Michaelis-Menten Constants of Neuraminidase with Nanogel Capillary Electrophoresis for the Determination of the Sialic Acid Linkage. 27936604 5 75 theme static 853:858 arg1 incubation 860:869 static incubation 853:869 static incubation 853:869 To circumvent the limitations of diffusion during static incubation, the incubation period is reproducibly achieved by varying the number of forward and reverse passes the substrate makes through the stationary fixed zone using in-capillary electrophoretic mixing. 27936604 5 76 theme stationary 1003:1012 arg1 zone 1020:1023 the stationary fixed zone 999:1023 the stationary fixed zone using in-capillary electrophoretic mixing 999:1065 To circumvent the limitations of diffusion during static incubation, the incubation period is reproducibly achieved by varying the number of forward and reverse passes the substrate makes through the stationary fixed zone using in-capillary electrophoretic mixing. 27936604 6 77 theme KM 1070:1071 arg1 value 1073:1077 A KM value 1068:1077 A KM value of 3.3 ± 0.8 mM (Vmax, 2100 ± 200 μM/min) 1068:1119 A KM value of 3.3 ± 0.8 mM (Vmax, 2100 ± 200 μM/min) was obtained for 3'-sialyllactose labeled with 2-aminobenzoic acid using neuraminidase from Clostridium perfringens that cleaves sialic acid monomers with an α2-3,6,8,9 linkage, which is similar to values reported in the literature that required benchtop analyses. 27936604 1 78 theme Phospholipid 160:171 arg1 nanogels 173:180 Phospholipid nanogels 160:180 Phospholipid nanogels 160:180 Phospholipid nanogels enhance the stability and performance of the exoglycosidase enzyme neuraminidase and are used to create a fixed zone of enzyme within a capillary. 27936604 6 79 theme 3.3 1082:1084 arg1 ± 1086:1086 ± 1086:1086 ± 1086:1086 A KM value of 3.3 ± 0.8 mM (Vmax, 2100 ± 200 μM/min) was obtained for 3'-sialyllactose labeled with 2-aminobenzoic acid using neuraminidase from Clostridium perfringens that cleaves sialic acid monomers with an α2-3,6,8,9 linkage, which is similar to values reported in the literature that required benchtop analyses. 27936604 0 80 theme Nanogel 76:82 arg1 Electrophoresis 94:108 Nanogel Capillary Electrophoresis 76:108 Nanogel Capillary Electrophoresis 76:108 Microscale Measurements of Michaelis-Menten Constants of Neuraminidase with Nanogel Capillary Electrophoresis for the Determination of the Sialic Acid Linkage. 27936604 5 81 theme fixed 1014:1018 arg1 zone 1020:1023 the stationary fixed zone 999:1023 the stationary fixed zone using in-capillary electrophoretic mixing 999:1065 To circumvent the limitations of diffusion during static incubation, the incubation period is reproducibly achieved by varying the number of forward and reverse passes the substrate makes through the stationary fixed zone using in-capillary electrophoretic mixing. 27936604 10 82 theme simple 1885:1890 arg1 electrophoresis 1839:1853 Nanogel electrophoresis 1831:1853 Nanogel electrophoresis 1831:1853 Nanogel electrophoresis is an inexpensive, rapid, and simple alternative to current technologies used to distinguish the composition of 3' and 6' sialic acid linkages. 27936604 10 82 theme simple 1885:1890 arg1 alternative 1892:1902 an inexpensive, rapid, and simple alternative 1858:1902 an inexpensive, rapid, and simple alternative to current technologies used to distinguish the composition of 3' and 6' sialic acid linkages 1858:1996 Nanogel electrophoresis is an inexpensive, rapid, and simple alternative to current technologies used to distinguish the composition of 3' and 6' sialic acid linkages. 27936604 8 83 theme sialic 1584:1589 arg1 linkages 1596:1603 2-3 sialic acid linkages 1580:1603 2-3 sialic acid linkages 1580:1603 An alternative neuraminidase selective for 2-3 sialic acid linkages generated a KM value of 3 ± 2 mM (Vmax, 900 ± 300 μM/min) for 3'-sialyllactose. 27936604 8 84 theme alternative 1540:1550 arg1 neuraminidase 1552:1564 An alternative neuraminidase 1537:1564 An alternative neuraminidase selective for 2-3 sialic acid linkages 1537:1603 An alternative neuraminidase selective for 2-3 sialic acid linkages generated a KM value of 3 ± 2 mM (Vmax, 900 ± 300 μM/min) for 3'-sialyllactose. 27643891 13 0 theme micrometer 3016:3025 arg1 proximity 3027:3035 micrometer proximity 3016:3035 micrometer proximity 3016:3035 Achieving true 4D nanoprinting involves advances in surface chemistry and instrumentation development, and to this end 4D micropatterns were produced in a microfluidic photoreactor that can position polymers composed of different monomers within micrometer proximity. 27643891 3 1 theme devices 674:680 arg1 assembly 623:630 the assembly 619:630 the assembly of next generation optical and electronic devices or substrates for tissue engineering 619:717 The control of organic materials at the nanoscale-level of spatial resolution could revolutionize the assembly of next generation optical and electronic devices or substrates for tissue engineering or enable fundamental biological or material science investigations. 27643891 5 2 from interfaces 1233:1242 arg1 formation 1220:1228 covalent bond formation 1206:1228 covalent bond formation at interfaces 1206:1242 Several challenges however preclude the integration of organic chemistry with conventional nanomanufacturing approaches, namely most nanolithography platforms would denature or destroy delicate organic and biologically active matter, confirming covalent bond formation at interfaces remains difficult, and finally, only a small handful of the reactions used to transform molecules in solution have been validated on surfaces. 27643891 13 3 theme surface 2822:2828 arg1 chemistry 2830:2838 surface chemistry 2822:2838 surface chemistry 2822:2838 Achieving true 4D nanoprinting involves advances in surface chemistry and instrumentation development, and to this end 4D micropatterns were produced in a microfluidic photoreactor that can position polymers composed of different monomers within micrometer proximity. 27643891 10 4 theme SPL 2308:2310 arg1 use 2282:2284 the use 2278:2284 the use of massively parallel SPL to create covalently immobilized patterns of organic materials using thermal, catalytic, photochemical, and force-accelerated reactions 2278:2446 Herein we describe the use of massively parallel SPL to create covalently immobilized patterns of organic materials using thermal, catalytic, photochemical, and force-accelerated reactions. 27643891 4 5 theme reference 900:908 arg1 frame 910:914 a nanoscale reference frame 888:914 a nanoscale reference frame through the formation of new covalent bonds 888:958 Organic chemistry provides the requisite control over the orientation and position of matter within a nanoscale reference frame through the formation of new covalent bonds. 27643891 13 6 theme true 2780:2783 arg1 nanoprinting 2788:2799 true 4D nanoprinting 2780:2799 true 4D nanoprinting 2780:2799 Achieving true 4D nanoprinting involves advances in surface chemistry and instrumentation development, and to this end 4D micropatterns were produced in a microfluidic photoreactor that can position polymers composed of different monomers within micrometer proximity. 27643891 7 7 from group 1611:1615 arg1 efforts 1594:1600 efforts 1594:1600 efforts from our group to reconcile nanolithography, and specifically massively parallel scanning probe lithography (SPL), with organic chemistry to further the goal of 4D organic nanoprinting 1594:1785 This Account describes efforts from our group to reconcile nanolithography, and specifically massively parallel scanning probe lithography (SPL), with organic chemistry to further the goal of 4D organic nanoprinting. 27643891 15 8 theme top-down 3353:3360 arg1 strategies 3362:3371 conventional top-down strategies 3340:3371 conventional top-down strategies for preparing electronics, bioarrays, and functional substrates 3340:3435 As this field continues to mature we can expect bottom-up 4D nanomanufacturing to begin supplanting conventional top-down strategies for preparing electronics, bioarrays, and functional substrates. 27643891 13 9 from advances 2810:2817 arg1 chemistry 2830:2838 surface chemistry 2822:2838 surface chemistry 2822:2838 Achieving true 4D nanoprinting involves advances in surface chemistry and instrumentation development, and to this end 4D micropatterns were produced in a microfluidic photoreactor that can position polymers composed of different monomers within micrometer proximity. 27643891 13 9 from advances 2810:2817 arg1 development 2860:2870 instrumentation development 2844:2870 instrumentation development 2844:2870 Achieving true 4D nanoprinting involves advances in surface chemistry and instrumentation development, and to this end 4D micropatterns were produced in a microfluidic photoreactor that can position polymers composed of different monomers within micrometer proximity. 27643891 3 10 theme tissue 700:705 arg1 engineering 707:717 tissue engineering 700:717 tissue engineering 700:717 The control of organic materials at the nanoscale-level of spatial resolution could revolutionize the assembly of next generation optical and electronic devices or substrates for tissue engineering or enable fundamental biological or material science investigations. 27643891 8 11 theme parallel 1798:1805 arg1 SPL 1807:1809 Massively parallel SPL 1788:1809 Massively parallel SPL 1788:1809 Massively parallel SPL involves arrays of elastomeric pyramids mounted onto piezoelectric actuators, and creates patterns with feature diameters below 50 nm by using the pyramidal tips for either the direct deposition of ink or the localized delivery of energy to a surface. 27643891 4 12 theme matter 874:879 arg1 position 862:869 position 862:869 position 862:869 Organic chemistry provides the requisite control over the orientation and position of matter within a nanoscale reference frame through the formation of new covalent bonds. 27643891 4 12 theme matter 874:879 arg1 orientation 846:856 orientation 846:856 orientation 846:856 Organic chemistry provides the requisite control over the orientation and position of matter within a nanoscale reference frame through the formation of new covalent bonds. 27643891 9 13 theme nanoscale 2223:2231 arg1 resolution 2241:2250 nanoscale spatial resolution 2223:2250 nanoscale spatial resolution in 3D 2223:2256 While other groups have focused on tip and array architetctures, our efforts have been on exploring their use for localizing organic chemistry on surfaces with nanoscale spatial resolution in 3D. 27643891 3 14 theme materials 544:552 arg1 control 525:531 The control 521:531 The control of organic materials at the nanoscale-level of spatial resolution 521:597 The control of organic materials at the nanoscale-level of spatial resolution could revolutionize the assembly of next generation optical and electronic devices or substrates for tissue engineering or enable fundamental biological or material science investigations. 27643891 7 15 theme organic 1722:1728 arg1 chemistry 1730:1738 organic chemistry 1722:1738 organic chemistry to further the goal of 4D organic nanoprinting 1722:1785 This Account describes efforts from our group to reconcile nanolithography, and specifically massively parallel scanning probe lithography (SPL), with organic chemistry to further the goal of 4D organic nanoprinting. 27643891 4 16 theme new 941:943 arg1 bonds 954:958 new covalent bonds 941:958 new covalent bonds 941:958 Organic chemistry provides the requisite control over the orientation and position of matter within a nanoscale reference frame through the formation of new covalent bonds. 27643891 5 17 from molecules 1332:1340 arg1 solution 1345:1352 solution 1345:1352 solution 1345:1352 Several challenges however preclude the integration of organic chemistry with conventional nanomanufacturing approaches, namely most nanolithography platforms would denature or destroy delicate organic and biologically active matter, confirming covalent bond formation at interfaces remains difficult, and finally, only a small handful of the reactions used to transform molecules in solution have been validated on surfaces. 27643891 3 18 theme fundamental 729:739 arg1 investigations 772:785 fundamental biological or material science investigations 729:785 investigations 772:785 The control of organic materials at the nanoscale-level of spatial resolution could revolutionize the assembly of next generation optical and electronic devices or substrates for tissue engineering or enable fundamental biological or material science investigations. 27643891 8 19 theme direct 1988:1993 arg1 deposition 1995:2004 the direct deposition 1984:2004 the direct deposition of ink 1984:2011 Massively parallel SPL involves arrays of elastomeric pyramids mounted onto piezoelectric actuators, and creates patterns with feature diameters below 50 nm by using the pyramidal tips for either the direct deposition of ink or the localized delivery of energy to a surface. 27643891 14 20 theme organic 3183:3189 arg1 chemistry 3191:3199 organic chemistry 3183:3199 organic chemistry 3183:3199 A substantial gap remains, however, between these current technologies and the future's 4D nanomanufacturing tools, but the marriage of SPL with organic chemistry is an important step toward this goal. 27643891 4 21 theme bonds 954:958 arg1 formation 928:936 the formation 924:936 the formation of new covalent bonds 924:958 Organic chemistry provides the requisite control over the orientation and position of matter within a nanoscale reference frame through the formation of new covalent bonds. 27643891 8 22 theme pyramids 1842:1849 arg1 arrays 1820:1825 arrays 1820:1825 arrays of elastomeric pyramids mounted onto piezoelectric actuators 1820:1886 Massively parallel SPL involves arrays of elastomeric pyramids mounted onto piezoelectric actuators, and creates patterns with feature diameters below 50 nm by using the pyramidal tips for either the direct deposition of ink or the localized delivery of energy to a surface. 27643891 10 23 theme force-accelerated 2420:2436 arg1 reactions 2438:2446 thermal, catalytic, photochemical, and force-accelerated reactions 2381:2446 thermal, catalytic, photochemical, and force-accelerated reactions 2381:2446 Herein we describe the use of massively parallel SPL to create covalently immobilized patterns of organic materials using thermal, catalytic, photochemical, and force-accelerated reactions. 27643891 16 24 theme sophistication 3598:3611 arg1 level 3581:3585 a level 3579:3585 a level of organic sophistication that is entirely unachievable using existing technologies 3579:3669 In addition, these new printing technologies may enable the preparation of synthetic targets, such as artificial biological interfaces, with a level of organic sophistication that is entirely unachievable using existing technologies. 27643891 3 25 theme science 764:770 arg1 investigations 772:785 fundamental biological or material science investigations 729:785 investigations 772:785 The control of organic materials at the nanoscale-level of spatial resolution could revolutionize the assembly of next generation optical and electronic devices or substrates for tissue engineering or enable fundamental biological or material science investigations. 27643891 5 26 theme most 1089:1092 arg1 platforms 1110:1118 namely most nanolithography platforms 1082:1118 namely most nanolithography platforms 1082:1118 Several challenges however preclude the integration of organic chemistry with conventional nanomanufacturing approaches, namely most nanolithography platforms would denature or destroy delicate organic and biologically active matter, confirming covalent bond formation at interfaces remains difficult, and finally, only a small handful of the reactions used to transform molecules in solution have been validated on surfaces. 27643891 1 27 theme complex 134:140 arg1 structure 164:172 complex four-dimensional (4D) structure 134:172 complex four-dimensional (4D) structure 134:172 Future nanomanufacturing tools will prepare organic materials with complex four-dimensional (4D) structure, where the position (x, y, z) and chemical composition within a volume is controlled with sub-1 μm spatial resolution. 27643891 16 28 theme printing 3461:3468 arg1 technologies 3470:3481 these new printing technologies 3451:3481 these new printing technologies 3451:3481 In addition, these new printing technologies may enable the preparation of synthetic targets, such as artificial biological interfaces, with a level of organic sophistication that is entirely unachievable using existing technologies. 27643891 12 29 theme brush 2738:2742 arg1 polymerizations 2744:2758 photochemical brush polymerizations 2724:2758 photochemical brush polymerizations 2724:2758 These efforts have resulted in new opportunities for the preparation of glycan arrays, novel approaches for covalently patterning graphene, and a 3D nanoprinter by combining photochemical brush polymerizations with SPL. 27643891 8 30 theme localized 2020:2028 arg1 delivery 2030:2037 the localized delivery 2016:2037 the localized delivery of energy to a surface 2016:2060 Massively parallel SPL involves arrays of elastomeric pyramids mounted onto piezoelectric actuators, and creates patterns with feature diameters below 50 nm by using the pyramidal tips for either the direct deposition of ink or the localized delivery of energy to a surface. 27643891 7 31 theme scanning 1683:1690 arg1 SPL 1711:1713 SPL 1711:1713 SPL 1711:1713 This Account describes efforts from our group to reconcile nanolithography, and specifically massively parallel scanning probe lithography (SPL), with organic chemistry to further the goal of 4D organic nanoprinting. 27643891 7 31 theme scanning 1683:1690 arg1 lithography 1698:1708 massively parallel scanning probe lithography 1664:1708 massively parallel scanning probe lithography (SPL) 1664:1714 This Account describes efforts from our group to reconcile nanolithography, and specifically massively parallel scanning probe lithography (SPL), with organic chemistry to further the goal of 4D organic nanoprinting. 27643891 12 32 dep patterning 2669:2678 arg1 graphene 2680:2687 graphene 2680:2687 covalently patterning graphene 2658:2687 These efforts have resulted in new opportunities for the preparation of glycan arrays, novel approaches for covalently patterning graphene, and a 3D nanoprinter by combining photochemical brush polymerizations with SPL. 27643891 11 33 theme bond 2534:2537 arg1 formation 2539:2547 interfacial bond formation 2522:2547 interfacial bond formation 2522:2547 In doing so, we have developed a high-throughput protocol for confirming interfacial bond formation. 27643891 3 34 theme resolution 588:597 arg1 nanoscale-level 561:575 the nanoscale-level 557:575 the nanoscale-level of spatial resolution 557:597 The control of organic materials at the nanoscale-level of spatial resolution could revolutionize the assembly of next generation optical and electronic devices or substrates for tissue engineering or enable fundamental biological or material science investigations. 27643891 13 35 theme microfluidic 2925:2936 arg1 photoreactor 2938:2949 a microfluidic photoreactor 2923:2949 a microfluidic photoreactor that can position polymers composed of different monomers within micrometer proximity 2923:3035 Achieving true 4D nanoprinting involves advances in surface chemistry and instrumentation development, and to this end 4D micropatterns were produced in a microfluidic photoreactor that can position polymers composed of different monomers within micrometer proximity. 27643891 9 36 theme other 2069:2073 arg1 groups 2075:2080 other groups 2069:2080 other groups 2069:2080 While other groups have focused on tip and array architetctures, our efforts have been on exploring their use for localizing organic chemistry on surfaces with nanoscale spatial resolution in 3D. 27643891 16 37 theme existing 3649:3656 arg1 technologies 3658:3669 existing technologies 3649:3669 existing technologies 3649:3669 In addition, these new printing technologies may enable the preparation of synthetic targets, such as artificial biological interfaces, with a level of organic sophistication that is entirely unachievable using existing technologies. 27643891 6 38 theme organic 1424:1430 arg1 transformations 1432:1446 organic transformations 1424:1446 organic transformations 1424:1446 Thus, entirely new approaches, where organic transformations and spatial control are considered equally important contributors, are needed to create 4D organic nanoprinting platforms. 27643891 7 39 theme nanoprinting 1774:1785 arg1 goal 1755:1758 further the goal 1743:1758 further the goal of 4D organic nanoprinting 1743:1785 This Account describes efforts from our group to reconcile nanolithography, and specifically massively parallel scanning probe lithography (SPL), with organic chemistry to further the goal of 4D organic nanoprinting. 27643891 2 40 theme sophisticated 488:500 arg1 events 513:518 the most sophisticated biological events 479:518 the most sophisticated biological events 479:518 Such tools could produce substrates that mimic biological interfaces, like the cell surface or the extracellular matrix, whose topology and chemical complexity combine to direct some of the most sophisticated biological events. 27643891 12 41 theme 3D 2696:2697 arg1 nanoprinter 2699:2709 a 3D nanoprinter 2694:2709 a 3D nanoprinter by combining photochemical brush polymerizations with SPL 2694:2767 These efforts have resulted in new opportunities for the preparation of glycan arrays, novel approaches for covalently patterning graphene, and a 3D nanoprinter by combining photochemical brush polymerizations with SPL. 27643891 5 42 theme organic 1155:1161 arg1 matter 1187:1192 delicate organic and biologically active matter 1146:1192 delicate organic and biologically active matter 1146:1192 Several challenges however preclude the integration of organic chemistry with conventional nanomanufacturing approaches, namely most nanolithography platforms would denature or destroy delicate organic and biologically active matter, confirming covalent bond formation at interfaces remains difficult, and finally, only a small handful of the reactions used to transform molecules in solution have been validated on surfaces. 27643891 8 43 theme feature 1915:1921 arg1 diameters 1923:1931 feature diameters 1915:1931 feature diameters 1915:1931 Massively parallel SPL involves arrays of elastomeric pyramids mounted onto piezoelectric actuators, and creates patterns with feature diameters below 50 nm by using the pyramidal tips for either the direct deposition of ink or the localized delivery of energy to a surface. 27643891 1 44 theme Future 67:72 arg1 tools 92:96 Future nanomanufacturing tools 67:96 Future nanomanufacturing tools 67:96 Future nanomanufacturing tools will prepare organic materials with complex four-dimensional (4D) structure, where the position (x, y, z) and chemical composition within a volume is controlled with sub-1 μm spatial resolution. 27643891 7 45 theme 4D 1763:1764 arg1 nanoprinting 1774:1785 4D organic nanoprinting 1763:1785 4D organic nanoprinting 1763:1785 This Account describes efforts from our group to reconcile nanolithography, and specifically massively parallel scanning probe lithography (SPL), with organic chemistry to further the goal of 4D organic nanoprinting. 27643891 4 46 theme Organic 788:794 arg1 chemistry 796:804 Organic chemistry 788:804 Organic chemistry 788:804 Organic chemistry provides the requisite control over the orientation and position of matter within a nanoscale reference frame through the formation of new covalent bonds. 27643891 6 47 theme new 1402:1404 arg1 approaches 1406:1415 entirely new approaches 1393:1415 entirely new approaches 1393:1415 Thus, entirely new approaches, where organic transformations and spatial control are considered equally important contributors, are needed to create 4D organic nanoprinting platforms. 27643891 6 48 theme spatial 1452:1458 arg1 control 1460:1466 spatial control 1452:1466 spatial control 1452:1466 Thus, entirely new approaches, where organic transformations and spatial control are considered equally important contributors, are needed to create 4D organic nanoprinting platforms. 27643891 10 49 theme thermal 2381:2387 arg1 reactions 2438:2446 thermal, catalytic, photochemical, and force-accelerated reactions 2381:2446 thermal, catalytic, photochemical, and force-accelerated reactions 2381:2446 Herein we describe the use of massively parallel SPL to create covalently immobilized patterns of organic materials using thermal, catalytic, photochemical, and force-accelerated reactions. 27643891 5 50 theme Several 961:967 arg1 challenges 969:978 Several challenges 961:978 Several challenges 961:978 Several challenges however preclude the integration of organic chemistry with conventional nanomanufacturing approaches, namely most nanolithography platforms would denature or destroy delicate organic and biologically active matter, confirming covalent bond formation at interfaces remains difficult, and finally, only a small handful of the reactions used to transform molecules in solution have been validated on surfaces. 27643891 16 51 theme artificial 3540:3549 arg1 interfaces 3562:3571 artificial biological interfaces 3540:3571 artificial biological interfaces 3540:3571 In addition, these new printing technologies may enable the preparation of synthetic targets, such as artificial biological interfaces, with a level of organic sophistication that is entirely unachievable using existing technologies. 27643891 6 52 theme important 1491:1499 arg1 contributors 1501:1512 equally important contributors 1483:1512 equally important contributors 1483:1512 Thus, entirely new approaches, where organic transformations and spatial control are considered equally important contributors, are needed to create 4D organic nanoprinting platforms. 27643891 3 53 theme next 635:638 arg1 generation 640:649 next generation 635:649 next generation 635:649 The control of organic materials at the nanoscale-level of spatial resolution could revolutionize the assembly of next generation optical and electronic devices or substrates for tissue engineering or enable fundamental biological or material science investigations. 27643891 1 54 dep position 185:192 arg1 z 201:201 z 201:201 z 201:201 Future nanomanufacturing tools will prepare organic materials with complex four-dimensional (4D) structure, where the position (x, y, z) and chemical composition within a volume is controlled with sub-1 μm spatial resolution. 27643891 1 54 dep position 185:192 arg1 y 198:198 y 198:198 y 198:198 Future nanomanufacturing tools will prepare organic materials with complex four-dimensional (4D) structure, where the position (x, y, z) and chemical composition within a volume is controlled with sub-1 μm spatial resolution. 27643891 1 54 dep position 185:192 arg1 x 195:195 x 195:195 x 195:195 Future nanomanufacturing tools will prepare organic materials with complex four-dimensional (4D) structure, where the position (x, y, z) and chemical composition within a volume is controlled with sub-1 μm spatial resolution. 27643891 0 55 theme Tip-Induced 28:38 arg1 Reactions 56:64 Tip-Induced Organic Surface Reactions 28:64 Tip-Induced Organic Surface Reactions 28:64 Toward 4D Nanoprinting with Tip-Induced Organic Surface Reactions. 27643891 5 56 theme bond 1215:1218 arg1 formation 1220:1228 covalent bond formation 1206:1228 covalent bond formation at interfaces 1206:1242 Several challenges however preclude the integration of organic chemistry with conventional nanomanufacturing approaches, namely most nanolithography platforms would denature or destroy delicate organic and biologically active matter, confirming covalent bond formation at interfaces remains difficult, and finally, only a small handful of the reactions used to transform molecules in solution have been validated on surfaces. 27643891 15 57 theme bottom-up 3288:3296 arg1 nanomanufacturing 3301:3317 bottom-up 4D nanomanufacturing 3288:3317 bottom-up 4D nanomanufacturing 3288:3317 As this field continues to mature we can expect bottom-up 4D nanomanufacturing to begin supplanting conventional top-down strategies for preparing electronics, bioarrays, and functional substrates. 27643891 0 58 with Nanoprinting 10:21 arg1 Reactions 56:64 Tip-Induced Organic Surface Reactions 28:64 Tip-Induced Organic Surface Reactions 28:64 Toward 4D Nanoprinting with Tip-Induced Organic Surface Reactions. 27643891 0 59 theme Surface 48:54 arg1 Reactions 56:64 Tip-Induced Organic Surface Reactions 28:64 Tip-Induced Organic Surface Reactions 28:64 Toward 4D Nanoprinting with Tip-Induced Organic Surface Reactions. 27643891 15 60 theme functional 3415:3424 arg1 substrates 3426:3435 functional substrates 3415:3435 functional substrates 3415:3435 As this field continues to mature we can expect bottom-up 4D nanomanufacturing to begin supplanting conventional top-down strategies for preparing electronics, bioarrays, and functional substrates. 27643891 9 61 with surfaces 2209:2216 arg1 resolution 2241:2250 nanoscale spatial resolution 2223:2250 nanoscale spatial resolution in 3D 2223:2256 While other groups have focused on tip and array architetctures, our efforts have been on exploring their use for localizing organic chemistry on surfaces with nanoscale spatial resolution in 3D. 27643891 3 62 theme electronic 663:672 arg1 devices 674:680 next generation optical and electronic devices 635:680 next generation optical and electronic devices 635:680 The control of organic materials at the nanoscale-level of spatial resolution could revolutionize the assembly of next generation optical and electronic devices or substrates for tissue engineering or enable fundamental biological or material science investigations. 27643891 13 63 theme instrumentation 2844:2858 arg1 development 2860:2870 instrumentation development 2844:2870 instrumentation development 2844:2870 Achieving true 4D nanoprinting involves advances in surface chemistry and instrumentation development, and to this end 4D micropatterns were produced in a microfluidic photoreactor that can position polymers composed of different monomers within micrometer proximity. 27643891 5 64 theme small 1283:1287 arg1 handful 1289:1295 only a small handful 1276:1295 only a small handful of the reactions used to transform molecules in solution 1276:1352 Several challenges however preclude the integration of organic chemistry with conventional nanomanufacturing approaches, namely most nanolithography platforms would denature or destroy delicate organic and biologically active matter, confirming covalent bond formation at interfaces remains difficult, and finally, only a small handful of the reactions used to transform molecules in solution have been validated on surfaces. 27643891 5 65 theme chemistry 1024:1032 arg1 integration 1001:1011 the integration 997:1011 the integration of organic chemistry with conventional nanomanufacturing approaches 997:1079 Several challenges however preclude the integration of organic chemistry with conventional nanomanufacturing approaches, namely most nanolithography platforms would denature or destroy delicate organic and biologically active matter, confirming covalent bond formation at interfaces remains difficult, and finally, only a small handful of the reactions used to transform molecules in solution have been validated on surfaces. 27643891 14 66 theme important 3207:3215 arg1 marriage 3162:3169 the marriage 3158:3169 the marriage of SPL with organic chemistry 3158:3199 A substantial gap remains, however, between these current technologies and the future's 4D nanomanufacturing tools, but the marriage of SPL with organic chemistry is an important step toward this goal. 27643891 14 66 theme important 3207:3215 arg1 step 3217:3220 an important step 3204:3220 an important step toward this goal 3204:3237 A substantial gap remains, however, between these current technologies and the future's 4D nanomanufacturing tools, but the marriage of SPL with organic chemistry is an important step toward this goal. 27643891 3 67 theme optical 651:657 arg1 devices 674:680 next generation optical and electronic devices 635:680 next generation optical and electronic devices 635:680 The control of organic materials at the nanoscale-level of spatial resolution could revolutionize the assembly of next generation optical and electronic devices or substrates for tissue engineering or enable fundamental biological or material science investigations. 27643891 4 68 theme requisite 819:827 arg1 control 829:835 the requisite control 815:835 the requisite control over the orientation and position of matter within a nanoscale reference frame through the formation of new covalent bonds 815:958 Organic chemistry provides the requisite control over the orientation and position of matter within a nanoscale reference frame through the formation of new covalent bonds. 27643891 2 69 theme biological 340:349 arg1 interfaces 351:360 biological interfaces 340:360 biological interfaces 340:360 Such tools could produce substrates that mimic biological interfaces, like the cell surface or the extracellular matrix, whose topology and chemical complexity combine to direct some of the most sophisticated biological events. 27643891 6 70 theme organic 1539:1545 arg1 platforms 1560:1568 4D organic nanoprinting platforms 1536:1568 4D organic nanoprinting platforms 1536:1568 Thus, entirely new approaches, where organic transformations and spatial control are considered equally important contributors, are needed to create 4D organic nanoprinting platforms. 27643891 5 71 theme conventional 1039:1050 arg1 approaches 1070:1079 conventional nanomanufacturing approaches 1039:1079 conventional nanomanufacturing approaches 1039:1079 Several challenges however preclude the integration of organic chemistry with conventional nanomanufacturing approaches, namely most nanolithography platforms would denature or destroy delicate organic and biologically active matter, confirming covalent bond formation at interfaces remains difficult, and finally, only a small handful of the reactions used to transform molecules in solution have been validated on surfaces. 27643891 8 72 with patterns 1901:1908 arg1 diameters 1923:1931 feature diameters 1915:1931 feature diameters 1915:1931 Massively parallel SPL involves arrays of elastomeric pyramids mounted onto piezoelectric actuators, and creates patterns with feature diameters below 50 nm by using the pyramidal tips for either the direct deposition of ink or the localized delivery of energy to a surface. 27643891 10 73 theme immobilized 2333:2343 arg1 patterns 2345:2352 covalently immobilized patterns 2322:2352 covalently immobilized patterns of organic materials using thermal, catalytic, photochemical, and force-accelerated reactions 2322:2446 Herein we describe the use of massively parallel SPL to create covalently immobilized patterns of organic materials using thermal, catalytic, photochemical, and force-accelerated reactions. 27643891 10 74 theme parallel 2299:2306 arg1 SPL 2308:2310 massively parallel SPL 2289:2310 massively parallel SPL 2289:2310 Herein we describe the use of massively parallel SPL to create covalently immobilized patterns of organic materials using thermal, catalytic, photochemical, and force-accelerated reactions. 27643891 16 75 theme targets 3523:3529 arg1 preparation 3498:3508 the preparation 3494:3508 the preparation of synthetic targets, such as artificial biological interfaces 3494:3571 In addition, these new printing technologies may enable the preparation of synthetic targets, such as artificial biological interfaces, with a level of organic sophistication that is entirely unachievable using existing technologies. 27643891 9 76 theme organic 2188:2194 arg1 chemistry 2196:2204 organic chemistry 2188:2204 organic chemistry 2188:2204 While other groups have focused on tip and array architetctures, our efforts have been on exploring their use for localizing organic chemistry on surfaces with nanoscale spatial resolution in 3D. 27643891 8 77 theme pyramidal 1958:1966 arg1 tips 1968:1971 the pyramidal tips 1954:1971 the pyramidal tips for either the direct deposition of ink or the localized delivery of energy to a surface 1954:2060 Massively parallel SPL involves arrays of elastomeric pyramids mounted onto piezoelectric actuators, and creates patterns with feature diameters below 50 nm by using the pyramidal tips for either the direct deposition of ink or the localized delivery of energy to a surface. 27643891 12 78 theme nanoprinter 2699:2709 arg1 preparation 2607:2617 the preparation 2603:2617 the preparation of glycan arrays, novel approaches for covalently patterning graphene, and a 3D nanoprinter by combining photochemical brush polymerizations with SPL 2603:2767 These efforts have resulted in new opportunities for the preparation of glycan arrays, novel approaches for covalently patterning graphene, and a 3D nanoprinter by combining photochemical brush polymerizations with SPL. 27643891 15 79 theme conventional 3340:3351 arg1 strategies 3362:3371 conventional top-down strategies 3340:3371 conventional top-down strategies for preparing electronics, bioarrays, and functional substrates 3340:3435 As this field continues to mature we can expect bottom-up 4D nanomanufacturing to begin supplanting conventional top-down strategies for preparing electronics, bioarrays, and functional substrates. 27643891 4 80 theme nanoscale 890:898 arg1 frame 910:914 a nanoscale reference frame 888:914 a nanoscale reference frame through the formation of new covalent bonds 888:958 Organic chemistry provides the requisite control over the orientation and position of matter within a nanoscale reference frame through the formation of new covalent bonds. 27643891 14 81 theme SPL 3174:3176 arg1 marriage 3162:3169 the marriage 3158:3169 the marriage of SPL with organic chemistry 3158:3199 A substantial gap remains, however, between these current technologies and the future's 4D nanomanufacturing tools, but the marriage of SPL with organic chemistry is an important step toward this goal. 27643891 14 81 theme SPL 3174:3176 arg1 step 3217:3220 an important step 3204:3220 an important step toward this goal 3204:3237 A substantial gap remains, however, between these current technologies and the future's 4D nanomanufacturing tools, but the marriage of SPL with organic chemistry is an important step toward this goal. 27643891 9 82 from resolution 2241:2250 arg1 3D 2255:2256 3D 2255:2256 3D 2255:2256 While other groups have focused on tip and array architetctures, our efforts have been on exploring their use for localizing organic chemistry on surfaces with nanoscale spatial resolution in 3D. 27643891 13 83 theme 4D 2785:2786 arg1 nanoprinting 2788:2799 true 4D nanoprinting 2780:2799 true 4D nanoprinting 2780:2799 Achieving true 4D nanoprinting involves advances in surface chemistry and instrumentation development, and to this end 4D micropatterns were produced in a microfluidic photoreactor that can position polymers composed of different monomers within micrometer proximity. 27643891 13 84 theme different 2990:2998 arg1 monomers 3000:3007 different monomers 2990:3007 different monomers 2990:3007 Achieving true 4D nanoprinting involves advances in surface chemistry and instrumentation development, and to this end 4D micropatterns were produced in a microfluidic photoreactor that can position polymers composed of different monomers within micrometer proximity. 27643891 10 85 theme materials 2365:2373 arg1 patterns 2345:2352 covalently immobilized patterns 2322:2352 covalently immobilized patterns of organic materials using thermal, catalytic, photochemical, and force-accelerated reactions 2322:2446 Herein we describe the use of massively parallel SPL to create covalently immobilized patterns of organic materials using thermal, catalytic, photochemical, and force-accelerated reactions. 27643891 12 86 theme new 2581:2583 arg1 opportunities 2585:2597 new opportunities 2581:2597 new opportunities for the preparation of glycan arrays, novel approaches for covalently patterning graphene, and a 3D nanoprinter by combining photochemical brush polymerizations with SPL 2581:2767 These efforts have resulted in new opportunities for the preparation of glycan arrays, novel approaches for covalently patterning graphene, and a 3D nanoprinter by combining photochemical brush polymerizations with SPL. 27643891 14 87 theme substantial 3040:3050 arg1 gap 3052:3054 A substantial gap 3038:3054 A substantial gap 3038:3054 A substantial gap remains, however, between these current technologies and the future's 4D nanomanufacturing tools, but the marriage of SPL with organic chemistry is an important step toward this goal. 27643891 3 88 theme organic 536:542 arg1 materials 544:552 organic materials 536:552 organic materials 536:552 The control of organic materials at the nanoscale-level of spatial resolution could revolutionize the assembly of next generation optical and electronic devices or substrates for tissue engineering or enable fundamental biological or material science investigations. 27643891 1 89 with materials 119:127 arg1 structure 164:172 complex four-dimensional (4D) structure 134:172 complex four-dimensional (4D) structure 134:172 Future nanomanufacturing tools will prepare organic materials with complex four-dimensional (4D) structure, where the position (x, y, z) and chemical composition within a volume is controlled with sub-1 μm spatial resolution. 27643891 9 90 theme spatial 2233:2239 arg1 resolution 2241:2250 nanoscale spatial resolution 2223:2250 nanoscale spatial resolution in 3D 2223:2256 While other groups have focused on tip and array architetctures, our efforts have been on exploring their use for localizing organic chemistry on surfaces with nanoscale spatial resolution in 3D. 27643891 4 91 dep orientation 846:856 arg1 the 842:844 the 842:844 the 842:844 Organic chemistry provides the requisite control over the orientation and position of matter within a nanoscale reference frame through the formation of new covalent bonds. 27643891 10 92 theme catalytic 2390:2398 arg1 reactions 2438:2446 thermal, catalytic, photochemical, and force-accelerated reactions 2381:2446 thermal, catalytic, photochemical, and force-accelerated reactions 2381:2446 Herein we describe the use of massively parallel SPL to create covalently immobilized patterns of organic materials using thermal, catalytic, photochemical, and force-accelerated reactions. 27643891 5 93 with integration 1001:1011 arg1 approaches 1070:1079 conventional nanomanufacturing approaches 1039:1079 conventional nanomanufacturing approaches 1039:1079 Several challenges however preclude the integration of organic chemistry with conventional nanomanufacturing approaches, namely most nanolithography platforms would denature or destroy delicate organic and biologically active matter, confirming covalent bond formation at interfaces remains difficult, and finally, only a small handful of the reactions used to transform molecules in solution have been validated on surfaces. 27643891 3 94 theme biological 741:750 arg1 investigations 772:785 fundamental biological or material science investigations 729:785 investigations 772:785 The control of organic materials at the nanoscale-level of spatial resolution could revolutionize the assembly of next generation optical and electronic devices or substrates for tissue engineering or enable fundamental biological or material science investigations. 27643891 8 95 theme ink 2009:2011 arg1 deposition 1995:2004 the direct deposition 1984:2004 the direct deposition of ink 1984:2011 Massively parallel SPL involves arrays of elastomeric pyramids mounted onto piezoelectric actuators, and creates patterns with feature diameters below 50 nm by using the pyramidal tips for either the direct deposition of ink or the localized delivery of energy to a surface. 27643891 8 95 theme ink 2009:2011 arg1 delivery 2030:2037 the localized delivery 2016:2037 the localized delivery of energy to a surface 2016:2060 Massively parallel SPL involves arrays of elastomeric pyramids mounted onto piezoelectric actuators, and creates patterns with feature diameters below 50 nm by using the pyramidal tips for either the direct deposition of ink or the localized delivery of energy to a surface. 27643891 12 96 theme glycan 2622:2627 arg1 arrays 2629:2634 glycan arrays 2622:2634 glycan arrays 2622:2634 These efforts have resulted in new opportunities for the preparation of glycan arrays, novel approaches for covalently patterning graphene, and a 3D nanoprinter by combining photochemical brush polymerizations with SPL. 27643891 4 97 theme covalent 945:952 arg1 bonds 954:958 new covalent bonds 941:958 new covalent bonds 941:958 Organic chemistry provides the requisite control over the orientation and position of matter within a nanoscale reference frame through the formation of new covalent bonds. 27643891 16 98 theme new 3457:3459 arg1 technologies 3470:3481 these new printing technologies 3451:3481 these new printing technologies 3451:3481 In addition, these new printing technologies may enable the preparation of synthetic targets, such as artificial biological interfaces, with a level of organic sophistication that is entirely unachievable using existing technologies. 27643891 11 99 theme high-throughput 2482:2496 arg1 protocol 2498:2505 a high-throughput protocol 2480:2505 a high-throughput protocol for confirming interfacial bond formation 2480:2547 In doing so, we have developed a high-throughput protocol for confirming interfacial bond formation. 27643891 14 100 theme nanomanufacturing 3129:3145 arg1 tools 3147:3151 the future's 4D nanomanufacturing tools 3113:3151 the future's 4D nanomanufacturing tools 3113:3151 A substantial gap remains, however, between these current technologies and the future's 4D nanomanufacturing tools, but the marriage of SPL with organic chemistry is an important step toward this goal. 27643891 5 101 theme delicate 1146:1153 arg1 matter 1187:1192 delicate organic and biologically active matter 1146:1192 delicate organic and biologically active matter 1146:1192 Several challenges however preclude the integration of organic chemistry with conventional nanomanufacturing approaches, namely most nanolithography platforms would denature or destroy delicate organic and biologically active matter, confirming covalent bond formation at interfaces remains difficult, and finally, only a small handful of the reactions used to transform molecules in solution have been validated on surfaces. 27643891 8 102 theme elastomeric 1830:1840 arg1 pyramids 1842:1849 elastomeric pyramids 1830:1849 elastomeric pyramids mounted onto piezoelectric actuators 1830:1886 Massively parallel SPL involves arrays of elastomeric pyramids mounted onto piezoelectric actuators, and creates patterns with feature diameters below 50 nm by using the pyramidal tips for either the direct deposition of ink or the localized delivery of energy to a surface. 27643891 7 103 theme probe 1692:1696 arg1 SPL 1711:1713 SPL 1711:1713 SPL 1711:1713 This Account describes efforts from our group to reconcile nanolithography, and specifically massively parallel scanning probe lithography (SPL), with organic chemistry to further the goal of 4D organic nanoprinting. 27643891 7 103 theme probe 1692:1696 arg1 lithography 1698:1708 massively parallel scanning probe lithography 1664:1708 massively parallel scanning probe lithography (SPL) 1664:1714 This Account describes efforts from our group to reconcile nanolithography, and specifically massively parallel scanning probe lithography (SPL), with organic chemistry to further the goal of 4D organic nanoprinting. 27643891 16 104 theme organic 3590:3596 arg1 sophistication 3598:3611 organic sophistication 3590:3611 organic sophistication that is entirely unachievable using existing technologies 3590:3669 In addition, these new printing technologies may enable the preparation of synthetic targets, such as artificial biological interfaces, with a level of organic sophistication that is entirely unachievable using existing technologies. 27643891 5 105 theme nanolithography 1094:1108 arg1 platforms 1110:1118 namely most nanolithography platforms 1082:1118 namely most nanolithography platforms 1082:1118 Several challenges however preclude the integration of organic chemistry with conventional nanomanufacturing approaches, namely most nanolithography platforms would denature or destroy delicate organic and biologically active matter, confirming covalent bond formation at interfaces remains difficult, and finally, only a small handful of the reactions used to transform molecules in solution have been validated on surfaces. 27643891 1 106 theme four-dimensional 142:157 arg1 structure 164:172 complex four-dimensional (4D) structure 134:172 complex four-dimensional (4D) structure 134:172 Future nanomanufacturing tools will prepare organic materials with complex four-dimensional (4D) structure, where the position (x, y, z) and chemical composition within a volume is controlled with sub-1 μm spatial resolution. 27643891 7 107 theme parallel 1674:1681 arg1 SPL 1711:1713 SPL 1711:1713 SPL 1711:1713 This Account describes efforts from our group to reconcile nanolithography, and specifically massively parallel scanning probe lithography (SPL), with organic chemistry to further the goal of 4D organic nanoprinting. 27643891 7 107 theme parallel 1674:1681 arg1 lithography 1698:1708 massively parallel scanning probe lithography 1664:1708 massively parallel scanning probe lithography (SPL) 1664:1714 This Account describes efforts from our group to reconcile nanolithography, and specifically massively parallel scanning probe lithography (SPL), with organic chemistry to further the goal of 4D organic nanoprinting. 27643891 10 108 theme photochemical 2401:2413 arg1 reactions 2438:2446 thermal, catalytic, photochemical, and force-accelerated reactions 2381:2446 thermal, catalytic, photochemical, and force-accelerated reactions 2381:2446 Herein we describe the use of massively parallel SPL to create covalently immobilized patterns of organic materials using thermal, catalytic, photochemical, and force-accelerated reactions. 27643891 11 109 theme interfacial 2522:2532 arg1 formation 2539:2547 interfacial bond formation 2522:2547 interfacial bond formation 2522:2547 In doing so, we have developed a high-throughput protocol for confirming interfacial bond formation. 27643891 8 110 theme energy 2042:2047 arg1 deposition 1995:2004 the direct deposition 1984:2004 the direct deposition of ink 1984:2011 Massively parallel SPL involves arrays of elastomeric pyramids mounted onto piezoelectric actuators, and creates patterns with feature diameters below 50 nm by using the pyramidal tips for either the direct deposition of ink or the localized delivery of energy to a surface. 27643891 8 110 theme energy 2042:2047 arg1 delivery 2030:2037 the localized delivery 2016:2037 the localized delivery of energy to a surface 2016:2060 Massively parallel SPL involves arrays of elastomeric pyramids mounted onto piezoelectric actuators, and creates patterns with feature diameters below 50 nm by using the pyramidal tips for either the direct deposition of ink or the localized delivery of energy to a surface. 27643891 3 111 theme spatial 580:586 arg1 resolution 588:597 spatial resolution 580:597 spatial resolution 580:597 The control of organic materials at the nanoscale-level of spatial resolution could revolutionize the assembly of next generation optical and electronic devices or substrates for tissue engineering or enable fundamental biological or material science investigations. 27643891 8 112 theme piezoelectric 1864:1876 arg1 actuators 1878:1886 piezoelectric actuators 1864:1886 piezoelectric actuators 1864:1886 Massively parallel SPL involves arrays of elastomeric pyramids mounted onto piezoelectric actuators, and creates patterns with feature diameters below 50 nm by using the pyramidal tips for either the direct deposition of ink or the localized delivery of energy to a surface. 27643891 1 113 theme 4D 160:161 arg1 structure 164:172 complex four-dimensional (4D) structure 134:172 complex four-dimensional (4D) structure 134:172 Future nanomanufacturing tools will prepare organic materials with complex four-dimensional (4D) structure, where the position (x, y, z) and chemical composition within a volume is controlled with sub-1 μm spatial resolution. 27643891 5 114 theme reactions 1304:1312 arg1 handful 1289:1295 only a small handful 1276:1295 only a small handful of the reactions used to transform molecules in solution 1276:1352 Several challenges however preclude the integration of organic chemistry with conventional nanomanufacturing approaches, namely most nanolithography platforms would denature or destroy delicate organic and biologically active matter, confirming covalent bond formation at interfaces remains difficult, and finally, only a small handful of the reactions used to transform molecules in solution have been validated on surfaces. 27643891 5 115 theme covalent 1206:1213 arg1 formation 1220:1228 covalent bond formation 1206:1228 covalent bond formation at interfaces 1206:1242 Several challenges however preclude the integration of organic chemistry with conventional nanomanufacturing approaches, namely most nanolithography platforms would denature or destroy delicate organic and biologically active matter, confirming covalent bond formation at interfaces remains difficult, and finally, only a small handful of the reactions used to transform molecules in solution have been validated on surfaces. 27643891 1 116 theme nanomanufacturing 74:90 arg1 tools 92:96 Future nanomanufacturing tools 67:96 Future nanomanufacturing tools 67:96 Future nanomanufacturing tools will prepare organic materials with complex four-dimensional (4D) structure, where the position (x, y, z) and chemical composition within a volume is controlled with sub-1 μm spatial resolution. 27643891 7 117 theme organic 1766:1772 arg1 nanoprinting 1774:1785 4D organic nanoprinting 1763:1785 4D organic nanoprinting 1763:1785 This Account describes efforts from our group to reconcile nanolithography, and specifically massively parallel scanning probe lithography (SPL), with organic chemistry to further the goal of 4D organic nanoprinting. 27643891 12 118 theme approaches 2643:2652 arg1 preparation 2607:2617 the preparation 2603:2617 the preparation of glycan arrays, novel approaches for covalently patterning graphene, and a 3D nanoprinter by combining photochemical brush polymerizations with SPL 2603:2767 These efforts have resulted in new opportunities for the preparation of glycan arrays, novel approaches for covalently patterning graphene, and a 3D nanoprinter by combining photochemical brush polymerizations with SPL. 27643891 0 119 theme 4D 7:8 arg1 Nanoprinting 10:21 4D Nanoprinting 7:21 4D Nanoprinting with Tip-Induced Organic Surface Reactions 7:64 Toward 4D Nanoprinting with Tip-Induced Organic Surface Reactions. 27643891 5 120 theme active 1180:1185 arg1 matter 1187:1192 delicate organic and biologically active matter 1146:1192 delicate organic and biologically active matter 1146:1192 Several challenges however preclude the integration of organic chemistry with conventional nanomanufacturing approaches, namely most nanolithography platforms would denature or destroy delicate organic and biologically active matter, confirming covalent bond formation at interfaces remains difficult, and finally, only a small handful of the reactions used to transform molecules in solution have been validated on surfaces. 27643891 16 121 theme biological 3551:3560 arg1 interfaces 3562:3571 artificial biological interfaces 3540:3571 artificial biological interfaces 3540:3571 In addition, these new printing technologies may enable the preparation of synthetic targets, such as artificial biological interfaces, with a level of organic sophistication that is entirely unachievable using existing technologies. 27643891 9 122 theme array 2106:2110 arg1 architetctures 2112:2125 array architetctures 2106:2125 array architetctures 2106:2125 While other groups have focused on tip and array architetctures, our efforts have been on exploring their use for localizing organic chemistry on surfaces with nanoscale spatial resolution in 3D. 27643891 14 123 theme future 3117:3122 arg1 tools 3147:3151 the future's 4D nanomanufacturing tools 3113:3151 the future's 4D nanomanufacturing tools 3113:3151 A substantial gap remains, however, between these current technologies and the future's 4D nanomanufacturing tools, but the marriage of SPL with organic chemistry is an important step toward this goal. 27643891 1 124 theme organic 111:117 arg1 materials 119:127 organic materials 111:127 organic materials with complex four-dimensional (4D) structure, where the position (x, y, z) and chemical composition within a volume is controlled with sub-1 μm spatial resolution 111:290 Future nanomanufacturing tools will prepare organic materials with complex four-dimensional (4D) structure, where the position (x, y, z) and chemical composition within a volume is controlled with sub-1 μm spatial resolution. 27643891 2 125 theme extracellular 392:404 arg1 matrix 406:411 the extracellular matrix 388:411 the extracellular matrix 388:411 Such tools could produce substrates that mimic biological interfaces, like the cell surface or the extracellular matrix, whose topology and chemical complexity combine to direct some of the most sophisticated biological events. 27643891 12 126 theme novel 2637:2641 arg1 approaches 2643:2652 novel approaches 2637:2652 novel approaches for covalently patterning graphene 2637:2687 These efforts have resulted in new opportunities for the preparation of glycan arrays, novel approaches for covalently patterning graphene, and a 3D nanoprinter by combining photochemical brush polymerizations with SPL. 27643891 3 127 from nanoscale-level 561:575 arg1 control 525:531 The control 521:531 The control of organic materials at the nanoscale-level of spatial resolution 521:597 The control of organic materials at the nanoscale-level of spatial resolution could revolutionize the assembly of next generation optical and electronic devices or substrates for tissue engineering or enable fundamental biological or material science investigations. 27643891 0 128 theme Organic 40:46 arg1 Reactions 56:64 Tip-Induced Organic Surface Reactions 28:64 Tip-Induced Organic Surface Reactions 28:64 Toward 4D Nanoprinting with Tip-Induced Organic Surface Reactions. 27643891 5 129 theme nanomanufacturing 1052:1068 arg1 approaches 1070:1079 conventional nanomanufacturing approaches 1039:1079 conventional nanomanufacturing approaches 1039:1079 Several challenges however preclude the integration of organic chemistry with conventional nanomanufacturing approaches, namely most nanolithography platforms would denature or destroy delicate organic and biologically active matter, confirming covalent bond formation at interfaces remains difficult, and finally, only a small handful of the reactions used to transform molecules in solution have been validated on surfaces. 27643891 2 130 theme chemical 433:440 arg1 complexity 442:451 chemical complexity 433:451 chemical complexity 433:451 Such tools could produce substrates that mimic biological interfaces, like the cell surface or the extracellular matrix, whose topology and chemical complexity combine to direct some of the most sophisticated biological events. 27643891 2 131 theme cell 372:375 arg1 surface 377:383 the cell surface 368:383 the cell surface 368:383 Such tools could produce substrates that mimic biological interfaces, like the cell surface or the extracellular matrix, whose topology and chemical complexity combine to direct some of the most sophisticated biological events. 27643891 14 132 theme current 3088:3094 arg1 technologies 3096:3107 these current technologies 3082:3107 these current technologies 3082:3107 A substantial gap remains, however, between these current technologies and the future's 4D nanomanufacturing tools, but the marriage of SPL with organic chemistry is an important step toward this goal. 27643891 1 133 theme spatial 273:279 arg1 resolution 281:290 spatial resolution 273:290 spatial resolution 273:290 Future nanomanufacturing tools will prepare organic materials with complex four-dimensional (4D) structure, where the position (x, y, z) and chemical composition within a volume is controlled with sub-1 μm spatial resolution. 27643891 15 134 theme 4D 3298:3299 arg1 nanomanufacturing 3301:3317 bottom-up 4D nanomanufacturing 3288:3317 bottom-up 4D nanomanufacturing 3288:3317 As this field continues to mature we can expect bottom-up 4D nanomanufacturing to begin supplanting conventional top-down strategies for preparing electronics, bioarrays, and functional substrates. 27643891 2 135 theme biological 502:511 arg1 events 513:518 the most sophisticated biological events 479:518 the most sophisticated biological events 479:518 Such tools could produce substrates that mimic biological interfaces, like the cell surface or the extracellular matrix, whose topology and chemical complexity combine to direct some of the most sophisticated biological events. 27643891 10 136 theme organic 2357:2363 arg1 materials 2365:2373 organic materials 2357:2373 organic materials using thermal, catalytic, photochemical, and force-accelerated reactions 2357:2446 Herein we describe the use of massively parallel SPL to create covalently immobilized patterns of organic materials using thermal, catalytic, photochemical, and force-accelerated reactions. 27643891 14 137 with marriage 3162:3169 arg1 chemistry 3191:3199 organic chemistry 3183:3199 organic chemistry 3183:3199 A substantial gap remains, however, between these current technologies and the future's 4D nanomanufacturing tools, but the marriage of SPL with organic chemistry is an important step toward this goal. 27643891 5 138 theme organic 1016:1022 arg1 chemistry 1024:1032 organic chemistry 1016:1032 organic chemistry 1016:1032 Several challenges however preclude the integration of organic chemistry with conventional nanomanufacturing approaches, namely most nanolithography platforms would denature or destroy delicate organic and biologically active matter, confirming covalent bond formation at interfaces remains difficult, and finally, only a small handful of the reactions used to transform molecules in solution have been validated on surfaces. 27643891 12 139 theme photochemical 2724:2736 arg1 polymerizations 2744:2758 photochemical brush polymerizations 2724:2758 photochemical brush polymerizations 2724:2758 These efforts have resulted in new opportunities for the preparation of glycan arrays, novel approaches for covalently patterning graphene, and a 3D nanoprinter by combining photochemical brush polymerizations with SPL. 27643891 2 140 theme Such 293:296 arg1 tools 298:302 Such tools 293:302 Such tools 293:302 Such tools could produce substrates that mimic biological interfaces, like the cell surface or the extracellular matrix, whose topology and chemical complexity combine to direct some of the most sophisticated biological events. 27643891 6 141 theme nanoprinting 1547:1558 arg1 platforms 1560:1568 4D organic nanoprinting platforms 1536:1568 4D organic nanoprinting platforms 1536:1568 Thus, entirely new approaches, where organic transformations and spatial control are considered equally important contributors, are needed to create 4D organic nanoprinting platforms. 27643891 12 142 theme arrays 2629:2634 arg1 preparation 2607:2617 the preparation 2603:2617 the preparation of glycan arrays, novel approaches for covalently patterning graphene, and a 3D nanoprinter by combining photochemical brush polymerizations with SPL 2603:2767 These efforts have resulted in new opportunities for the preparation of glycan arrays, novel approaches for covalently patterning graphene, and a 3D nanoprinter by combining photochemical brush polymerizations with SPL. 27643891 16 143 theme synthetic 3513:3521 arg1 interfaces 3562:3571 artificial biological interfaces 3540:3571 artificial biological interfaces 3540:3571 In addition, these new printing technologies may enable the preparation of synthetic targets, such as artificial biological interfaces, with a level of organic sophistication that is entirely unachievable using existing technologies. 27643891 16 143 theme synthetic 3513:3521 arg1 targets 3523:3529 synthetic targets 3513:3529 synthetic targets 3513:3529 In addition, these new printing technologies may enable the preparation of synthetic targets, such as artificial biological interfaces, with a level of organic sophistication that is entirely unachievable using existing technologies. 27643891 3 144 theme substrates 685:694 arg1 assembly 623:630 the assembly 619:630 the assembly of next generation optical and electronic devices or substrates for tissue engineering 619:717 The control of organic materials at the nanoscale-level of spatial resolution could revolutionize the assembly of next generation optical and electronic devices or substrates for tissue engineering or enable fundamental biological or material science investigations. 27643891 14 145 theme 4D 3126:3127 arg1 tools 3147:3151 the future's 4D nanomanufacturing tools 3113:3151 the future's 4D nanomanufacturing tools 3113:3151 A substantial gap remains, however, between these current technologies and the future's 4D nanomanufacturing tools, but the marriage of SPL with organic chemistry is an important step toward this goal. 27643891 6 146 theme 4D 1536:1537 arg1 platforms 1560:1568 4D organic nanoprinting platforms 1536:1568 4D organic nanoprinting platforms 1536:1568 Thus, entirely new approaches, where organic transformations and spatial control are considered equally important contributors, are needed to create 4D organic nanoprinting platforms. 27643891 1 147 theme chemical 208:215 arg1 composition 217:227 chemical composition 208:227 chemical composition 208:227 Future nanomanufacturing tools will prepare organic materials with complex four-dimensional (4D) structure, where the position (x, y, z) and chemical composition within a volume is controlled with sub-1 μm spatial resolution. 27441255 4 0 theme unit 830:833 arg1 backbone 868:875 a disaccharide repeating unit [→ α-D-GalpA-1,2-α-L-Rhap-1,4 →] backbone 805:875 a disaccharide repeating unit [→ α-D-GalpA-1,2-α-L-Rhap-1,4 →] backbone 805:875 The rhamnogalacturonan I (RG-I) are consisted of a disaccharide repeating unit [→ α-D-GalpA-1,2-α-L-Rhap-1,4 →] backbone, with side chains contained highly branched α-(1 → 5)-linked arabinan and short linear β-(1 → 4)-linked galactan, attached to O-4 of the rhamnosyl residues. 27441255 3 1 from presence 656:663 arg1 fraction 746:753 both pectin fraction 734:753 both pectin fraction 734:753 The data reveal the presence of altering homogalacturonan (HG) and rhamnogalacturonan I (RG-I) in both pectin fraction. 27441255 1 2 theme monosaccharide 318:331 arg1 composition 333:343 monosaccharide composition 318:343 monosaccharide composition 318:343 The pectin polysaccharides from leaves of Argania spinosa (L.) Skeels, collected from Stidia area in the west coast of northern Algeria, were investigated by using sequential extractions and the resulting fractions were analysed for monosaccharide composition and chemical structure. 27441255 4 3 theme repeating 820:828 arg1 backbone 868:875 a disaccharide repeating unit [→ α-D-GalpA-1,2-α-L-Rhap-1,4 →] backbone 805:875 a disaccharide repeating unit [→ α-D-GalpA-1,2-α-L-Rhap-1,4 →] backbone 805:875 The rhamnogalacturonan I (RG-I) are consisted of a disaccharide repeating unit [→ α-D-GalpA-1,2-α-L-Rhap-1,4 →] backbone, with side chains contained highly branched α-(1 → 5)-linked arabinan and short linear β-(1 → 4)-linked galactan, attached to O-4 of the rhamnosyl residues. 27441255 4 4 dep -linked 973:979 arg1 β- 964:965 short linear β- 951:965 short linear β- 951:965 The rhamnogalacturonan I (RG-I) are consisted of a disaccharide repeating unit [→ α-D-GalpA-1,2-α-L-Rhap-1,4 →] backbone, with side chains contained highly branched α-(1 → 5)-linked arabinan and short linear β-(1 → 4)-linked galactan, attached to O-4 of the rhamnosyl residues. 27441255 4 4 dep -linked 973:979 arg1 → 969:969 1 → 4 967:971 1 → 4 967:971 The rhamnogalacturonan I (RG-I) are consisted of a disaccharide repeating unit [→ α-D-GalpA-1,2-α-L-Rhap-1,4 →] backbone, with side chains contained highly branched α-(1 → 5)-linked arabinan and short linear β-(1 → 4)-linked galactan, attached to O-4 of the rhamnosyl residues. 27441255 4 4 dep -linked 973:979 arg1 arabinan 938:945 arabinan 938:945 arabinan 938:945 The rhamnogalacturonan I (RG-I) are consisted of a disaccharide repeating unit [→ α-D-GalpA-1,2-α-L-Rhap-1,4 →] backbone, with side chains contained highly branched α-(1 → 5)-linked arabinan and short linear β-(1 → 4)-linked galactan, attached to O-4 of the rhamnosyl residues. 27441255 4 5 dep -linked 930:936 arg1 → 926:926 1 → 5 924:928 1 → 5 924:928 The rhamnogalacturonan I (RG-I) are consisted of a disaccharide repeating unit [→ α-D-GalpA-1,2-α-L-Rhap-1,4 →] backbone, with side chains contained highly branched α-(1 → 5)-linked arabinan and short linear β-(1 → 4)-linked galactan, attached to O-4 of the rhamnosyl residues. 27441255 4 5 dep -linked 930:936 arg1 -linked 973:979 -linked 973:979 -linked 973:979 The rhamnogalacturonan I (RG-I) are consisted of a disaccharide repeating unit [→ α-D-GalpA-1,2-α-L-Rhap-1,4 →] backbone, with side chains contained highly branched α-(1 → 5)-linked arabinan and short linear β-(1 → 4)-linked galactan, attached to O-4 of the rhamnosyl residues. 27441255 4 5 dep -linked 930:936 arg1 branched 912:919 branched 912:919 branched 912:919 The rhamnogalacturonan I (RG-I) are consisted of a disaccharide repeating unit [→ α-D-GalpA-1,2-α-L-Rhap-1,4 →] backbone, with side chains contained highly branched α-(1 → 5)-linked arabinan and short linear β-(1 → 4)-linked galactan, attached to O-4 of the rhamnosyl residues. 27441255 4 6 attach attached 991:998 arg1 O-4 1003:1005 O-4 1003:1005 O-4 of the rhamnosyl residues 1003:1031 The rhamnogalacturonan I (RG-I) are consisted of a disaccharide repeating unit [→ α-D-GalpA-1,2-α-L-Rhap-1,4 →] backbone, with side chains contained highly branched α-(1 → 5)-linked arabinan and short linear β-(1 → 4)-linked galactan, attached to O-4 of the rhamnosyl residues. 27441255 4 6 attach attached 991:998 arg2 galactan 981:988 highly branched α-(1 → 5)-linked arabinan and short linear β-(1 → 4)-linked galactan 905:988 highly branched α-(1 → 5)-linked arabinan and short linear β-(1 → 4)-linked galactan 905:988 The rhamnogalacturonan I (RG-I) are consisted of a disaccharide repeating unit [→ α-D-GalpA-1,2-α-L-Rhap-1,4 →] backbone, with side chains contained highly branched α-(1 → 5)-linked arabinan and short linear β-(1 → 4)-linked galactan, attached to O-4 of the rhamnosyl residues. 27441255 4 7 theme [→ 835:836 arg1 backbone 868:875 a disaccharide repeating unit [→ α-D-GalpA-1,2-α-L-Rhap-1,4 →] backbone 805:875 a disaccharide repeating unit [→ α-D-GalpA-1,2-α-L-Rhap-1,4 →] backbone 805:875 The rhamnogalacturonan I (RG-I) are consisted of a disaccharide repeating unit [→ α-D-GalpA-1,2-α-L-Rhap-1,4 →] backbone, with side chains contained highly branched α-(1 → 5)-linked arabinan and short linear β-(1 → 4)-linked galactan, attached to O-4 of the rhamnosyl residues. 27441255 1 8 dep spinosa 135:141 arg1 L. 144:145 L. 144:145 L. 144:145 The pectin polysaccharides from leaves of Argania spinosa (L.) Skeels, collected from Stidia area in the west coast of northern Algeria, were investigated by using sequential extractions and the resulting fractions were analysed for monosaccharide composition and chemical structure. 27441255 4 9 theme -linked 930:936 arg1 galactan 981:988 highly branched α-(1 → 5)-linked arabinan and short linear β-(1 → 4)-linked galactan 905:988 highly branched α-(1 → 5)-linked arabinan and short linear β-(1 → 4)-linked galactan 905:988 The rhamnogalacturonan I (RG-I) are consisted of a disaccharide repeating unit [→ α-D-GalpA-1,2-α-L-Rhap-1,4 →] backbone, with side chains contained highly branched α-(1 → 5)-linked arabinan and short linear β-(1 → 4)-linked galactan, attached to O-4 of the rhamnosyl residues. 27441255 1 10 theme chemical 349:356 arg1 structure 358:366 chemical structure 349:366 chemical structure 349:366 The pectin polysaccharides from leaves of Argania spinosa (L.) Skeels, collected from Stidia area in the west coast of northern Algeria, were investigated by using sequential extractions and the resulting fractions were analysed for monosaccharide composition and chemical structure. 27441255 2 11 theme C 616:616 arg1 spectroscopy 622:633 (13)C NMR spectroscopy 612:633 (13)C NMR spectroscopy 612:633 Water-soluble pectic (ALS-WSP) and chelating-soluble pectic (ALS-CSP) fractions were obtained, de-esterified and fractionated by anion-exchange chromatography and characterized by sugar analysis combined with methylation analysis and (1)H and (13)C NMR spectroscopy. 27441255 2 12 theme NMR 618:620 arg1 spectroscopy 622:633 (13)C NMR spectroscopy 612:633 (13)C NMR spectroscopy 612:633 Water-soluble pectic (ALS-WSP) and chelating-soluble pectic (ALS-CSP) fractions were obtained, de-esterified and fractionated by anion-exchange chromatography and characterized by sugar analysis combined with methylation analysis and (1)H and (13)C NMR spectroscopy. 27441255 4 13 theme residues 1024:1031 arg1 O-4 1003:1005 O-4 1003:1005 O-4 of the rhamnosyl residues 1003:1031 The rhamnogalacturonan I (RG-I) are consisted of a disaccharide repeating unit [→ α-D-GalpA-1,2-α-L-Rhap-1,4 →] backbone, with side chains contained highly branched α-(1 → 5)-linked arabinan and short linear β-(1 → 4)-linked galactan, attached to O-4 of the rhamnosyl residues. 27441255 2 14 dep H 606:606 arg1 1 604:604 1 604:604 1 604:604 Water-soluble pectic (ALS-WSP) and chelating-soluble pectic (ALS-CSP) fractions were obtained, de-esterified and fractionated by anion-exchange chromatography and characterized by sugar analysis combined with methylation analysis and (1)H and (13)C NMR spectroscopy. 27441255 4 15 theme linear 957:962 arg1 β- 964:965 short linear β- 951:965 short linear β- 951:965 The rhamnogalacturonan I (RG-I) are consisted of a disaccharide repeating unit [→ α-D-GalpA-1,2-α-L-Rhap-1,4 →] backbone, with side chains contained highly branched α-(1 → 5)-linked arabinan and short linear β-(1 → 4)-linked galactan, attached to O-4 of the rhamnosyl residues. 27441255 0 16 theme structural 8:17 arg1 characterization 19:34 Partial structural characterization 0:34 Partial structural characterization of pectin cell wall from Argania spinosa 0:75 Partial structural characterization of pectin cell wall from Argania spinosa leaves. 27441255 4 17 theme disaccharide 807:818 arg1 backbone 868:875 a disaccharide repeating unit [→ α-D-GalpA-1,2-α-L-Rhap-1,4 →] backbone 805:875 a disaccharide repeating unit [→ α-D-GalpA-1,2-α-L-Rhap-1,4 →] backbone 805:875 The rhamnogalacturonan I (RG-I) are consisted of a disaccharide repeating unit [→ α-D-GalpA-1,2-α-L-Rhap-1,4 →] backbone, with side chains contained highly branched α-(1 → 5)-linked arabinan and short linear β-(1 → 4)-linked galactan, attached to O-4 of the rhamnosyl residues. 27441255 3 18 theme rhamnogalacturonan 703:720 arg1 RG-I 725:728 RG-I 725:728 RG-I 725:728 The data reveal the presence of altering homogalacturonan (HG) and rhamnogalacturonan I (RG-I) in both pectin fraction. 27441255 3 18 theme rhamnogalacturonan 703:720 arg1 I 722:722 rhamnogalacturonan I 703:722 rhamnogalacturonan I (RG-I) 703:729 The data reveal the presence of altering homogalacturonan (HG) and rhamnogalacturonan I (RG-I) in both pectin fraction. 27441255 0 19 theme Partial 0:6 arg1 characterization 19:34 Partial structural characterization 0:34 Partial structural characterization of pectin cell wall from Argania spinosa 0:75 Partial structural characterization of pectin cell wall from Argania spinosa leaves. 27441255 4 20 link -linked 930:936 arg1 galactan 981:988 highly branched α-(1 → 5)-linked arabinan and short linear β-(1 → 4)-linked galactan 905:988 highly branched α-(1 → 5)-linked arabinan and short linear β-(1 → 4)-linked galactan 905:988 The rhamnogalacturonan I (RG-I) are consisted of a disaccharide repeating unit [→ α-D-GalpA-1,2-α-L-Rhap-1,4 →] backbone, with side chains contained highly branched α-(1 → 5)-linked arabinan and short linear β-(1 → 4)-linked galactan, attached to O-4 of the rhamnosyl residues. 27441255 1 21 from leaves 117:122 arg1 polysaccharides 96:110 The pectin polysaccharides 85:110 The pectin polysaccharides 85:110 The pectin polysaccharides from leaves of Argania spinosa (L.) Skeels, collected from Stidia area in the west coast of northern Algeria, were investigated by using sequential extractions and the resulting fractions were analysed for monosaccharide composition and chemical structure. 27441255 1 22 theme pectin 89:94 arg1 polysaccharides 96:110 The pectin polysaccharides 85:110 The pectin polysaccharides 85:110 The pectin polysaccharides from leaves of Argania spinosa (L.) Skeels, collected from Stidia area in the west coast of northern Algeria, were investigated by using sequential extractions and the resulting fractions were analysed for monosaccharide composition and chemical structure. 27441255 1 23 theme Stidia 171:176 arg1 area 178:181 Stidia area 171:181 Stidia area 171:181 The pectin polysaccharides from leaves of Argania spinosa (L.) Skeels, collected from Stidia area in the west coast of northern Algeria, were investigated by using sequential extractions and the resulting fractions were analysed for monosaccharide composition and chemical structure. 27441255 2 24 theme ALS-CSP 430:436 arg1 fractions 439:447 Water-soluble pectic (ALS-WSP) and chelating-soluble pectic (ALS-CSP) fractions 369:447 fractions 439:447 Water-soluble pectic (ALS-WSP) and chelating-soluble pectic (ALS-CSP) fractions were obtained, de-esterified and fractionated by anion-exchange chromatography and characterized by sugar analysis combined with methylation analysis and (1)H and (13)C NMR spectroscopy. 27441255 1 25 theme sequential 249:258 arg1 extractions 260:270 sequential extractions 249:270 sequential extractions 249:270 The pectin polysaccharides from leaves of Argania spinosa (L.) Skeels, collected from Stidia area in the west coast of northern Algeria, were investigated by using sequential extractions and the resulting fractions were analysed for monosaccharide composition and chemical structure. 27441255 4 26 theme side 883:886 arg1 chains 888:893 side chains 883:893 side chains 883:893 The rhamnogalacturonan I (RG-I) are consisted of a disaccharide repeating unit [→ α-D-GalpA-1,2-α-L-Rhap-1,4 →] backbone, with side chains contained highly branched α-(1 → 5)-linked arabinan and short linear β-(1 → 4)-linked galactan, attached to O-4 of the rhamnosyl residues. 27441255 4 27 contain contained 895:903 arg1 chains 888:893 side chains 883:893 side chains 883:893 The rhamnogalacturonan I (RG-I) are consisted of a disaccharide repeating unit [→ α-D-GalpA-1,2-α-L-Rhap-1,4 →] backbone, with side chains contained highly branched α-(1 → 5)-linked arabinan and short linear β-(1 → 4)-linked galactan, attached to O-4 of the rhamnosyl residues. 27441255 4 27 contain contained 895:903 arg2 galactan 981:988 highly branched α-(1 → 5)-linked arabinan and short linear β-(1 → 4)-linked galactan 905:988 highly branched α-(1 → 5)-linked arabinan and short linear β-(1 → 4)-linked galactan 905:988 The rhamnogalacturonan I (RG-I) are consisted of a disaccharide repeating unit [→ α-D-GalpA-1,2-α-L-Rhap-1,4 →] backbone, with side chains contained highly branched α-(1 → 5)-linked arabinan and short linear β-(1 → 4)-linked galactan, attached to O-4 of the rhamnosyl residues. 27441255 2 28 theme pectic 422:427 arg1 fractions 439:447 Water-soluble pectic (ALS-WSP) and chelating-soluble pectic (ALS-CSP) fractions 369:447 fractions 439:447 Water-soluble pectic (ALS-WSP) and chelating-soluble pectic (ALS-CSP) fractions were obtained, de-esterified and fractionated by anion-exchange chromatography and characterized by sugar analysis combined with methylation analysis and (1)H and (13)C NMR spectroscopy. 27441255 4 29 dep consisted 792:800 arg1 with 878:881 with 878:881 with 878:881 The rhamnogalacturonan I (RG-I) are consisted of a disaccharide repeating unit [→ α-D-GalpA-1,2-α-L-Rhap-1,4 →] backbone, with side chains contained highly branched α-(1 → 5)-linked arabinan and short linear β-(1 → 4)-linked galactan, attached to O-4 of the rhamnosyl residues. 27441255 4 30 theme rhamnosyl 1014:1022 arg1 residues 1024:1031 the rhamnosyl residues 1010:1031 the rhamnosyl residues 1010:1031 The rhamnogalacturonan I (RG-I) are consisted of a disaccharide repeating unit [→ α-D-GalpA-1,2-α-L-Rhap-1,4 →] backbone, with side chains contained highly branched α-(1 → 5)-linked arabinan and short linear β-(1 → 4)-linked galactan, attached to O-4 of the rhamnosyl residues. 27441255 2 31 theme chelating-soluble 404:420 arg1 fractions 439:447 Water-soluble pectic (ALS-WSP) and chelating-soluble pectic (ALS-CSP) fractions 369:447 fractions 439:447 Water-soluble pectic (ALS-WSP) and chelating-soluble pectic (ALS-CSP) fractions were obtained, de-esterified and fractionated by anion-exchange chromatography and characterized by sugar analysis combined with methylation analysis and (1)H and (13)C NMR spectroscopy. 27441255 0 32 theme cell 46:49 arg1 wall 51:54 pectin cell wall 39:54 pectin cell wall 39:54 Partial structural characterization of pectin cell wall from Argania spinosa leaves. 27441255 4 33 dep RG-I 782:785 arg1 are 788:790 are 788:790 are 788:790 The rhamnogalacturonan I (RG-I) are consisted of a disaccharide repeating unit [→ α-D-GalpA-1,2-α-L-Rhap-1,4 →] backbone, with side chains contained highly branched α-(1 → 5)-linked arabinan and short linear β-(1 → 4)-linked galactan, attached to O-4 of the rhamnosyl residues. 27441255 0 34 theme pectin 39:44 arg1 wall 51:54 pectin cell wall 39:54 pectin cell wall 39:54 Partial structural characterization of pectin cell wall from Argania spinosa leaves. 27441255 3 35 theme pectin 739:744 arg1 fraction 746:753 both pectin fraction 734:753 both pectin fraction 734:753 The data reveal the presence of altering homogalacturonan (HG) and rhamnogalacturonan I (RG-I) in both pectin fraction. 27441255 2 36 theme sugar 549:553 arg1 analysis 555:562 sugar analysis 549:562 sugar analysis combined with methylation analysis and (1)H 549:606 Water-soluble pectic (ALS-WSP) and chelating-soluble pectic (ALS-CSP) fractions were obtained, de-esterified and fractionated by anion-exchange chromatography and characterized by sugar analysis combined with methylation analysis and (1)H and (13)C NMR spectroscopy. 27441255 0 37 from spinosa 69:75 arg1 characterization 19:34 Partial structural characterization 0:34 Partial structural characterization of pectin cell wall from Argania spinosa 0:75 Partial structural characterization of pectin cell wall from Argania spinosa leaves. 27441255 1 38 theme west 190:193 arg1 coast 195:199 the west coast 186:199 the west coast of northern Algeria 186:219 The pectin polysaccharides from leaves of Argania spinosa (L.) Skeels, collected from Stidia area in the west coast of northern Algeria, were investigated by using sequential extractions and the resulting fractions were analysed for monosaccharide composition and chemical structure. 27441255 4 39 theme short 951:955 arg1 β- 964:965 short linear β- 951:965 short linear β- 951:965 The rhamnogalacturonan I (RG-I) are consisted of a disaccharide repeating unit [→ α-D-GalpA-1,2-α-L-Rhap-1,4 →] backbone, with side chains contained highly branched α-(1 → 5)-linked arabinan and short linear β-(1 → 4)-linked galactan, attached to O-4 of the rhamnosyl residues. 27441255 1 40 theme resulting 280:288 arg1 fractions 290:298 the resulting fractions 276:298 the resulting fractions 276:298 The pectin polysaccharides from leaves of Argania spinosa (L.) Skeels, collected from Stidia area in the west coast of northern Algeria, were investigated by using sequential extractions and the resulting fractions were analysed for monosaccharide composition and chemical structure. 27441255 0 41 theme wall 51:54 arg1 characterization 19:34 Partial structural characterization 0:34 Partial structural characterization of pectin cell wall from Argania spinosa 0:75 Partial structural characterization of pectin cell wall from Argania spinosa leaves. 27441255 4 42 theme → 865:865 arg1 backbone 868:875 a disaccharide repeating unit [→ α-D-GalpA-1,2-α-L-Rhap-1,4 →] backbone 805:875 a disaccharide repeating unit [→ α-D-GalpA-1,2-α-L-Rhap-1,4 →] backbone 805:875 The rhamnogalacturonan I (RG-I) are consisted of a disaccharide repeating unit [→ α-D-GalpA-1,2-α-L-Rhap-1,4 →] backbone, with side chains contained highly branched α-(1 → 5)-linked arabinan and short linear β-(1 → 4)-linked galactan, attached to O-4 of the rhamnosyl residues. 27441255 4 43 theme α-D-GalpA-1,2-α-L-Rhap-1,4 838:863 arg1 backbone 868:875 a disaccharide repeating unit [→ α-D-GalpA-1,2-α-L-Rhap-1,4 →] backbone 805:875 a disaccharide repeating unit [→ α-D-GalpA-1,2-α-L-Rhap-1,4 →] backbone 805:875 The rhamnogalacturonan I (RG-I) are consisted of a disaccharide repeating unit [→ α-D-GalpA-1,2-α-L-Rhap-1,4 →] backbone, with side chains contained highly branched α-(1 → 5)-linked arabinan and short linear β-(1 → 4)-linked galactan, attached to O-4 of the rhamnosyl residues. 27441255 2 44 theme methylation 578:588 arg1 analysis 590:597 methylation analysis 578:597 methylation analysis 578:597 Water-soluble pectic (ALS-WSP) and chelating-soluble pectic (ALS-CSP) fractions were obtained, de-esterified and fractionated by anion-exchange chromatography and characterized by sugar analysis combined with methylation analysis and (1)H and (13)C NMR spectroscopy. 27441255 1 45 theme spinosa 135:141 arg1 Skeels 148:153 Argania spinosa (L.) Skeels 127:153 Argania spinosa (L.) Skeels 127:153 The pectin polysaccharides from leaves of Argania spinosa (L.) Skeels, collected from Stidia area in the west coast of northern Algeria, were investigated by using sequential extractions and the resulting fractions were analysed for monosaccharide composition and chemical structure. 27441255 2 46 theme anion-exchange 498:511 arg1 chromatography 513:526 anion-exchange chromatography 498:526 anion-exchange chromatography 498:526 Water-soluble pectic (ALS-WSP) and chelating-soluble pectic (ALS-CSP) fractions were obtained, de-esterified and fractionated by anion-exchange chromatography and characterized by sugar analysis combined with methylation analysis and (1)H and (13)C NMR spectroscopy. 27441255 4 47 theme I 779:779 arg1 RG-I 782:785 The rhamnogalacturonan I (RG-I) are 756:790 The rhamnogalacturonan I (RG-I) are 756:790 The rhamnogalacturonan I (RG-I) are consisted of a disaccharide repeating unit [→ α-D-GalpA-1,2-α-L-Rhap-1,4 →] backbone, with side chains contained highly branched α-(1 → 5)-linked arabinan and short linear β-(1 → 4)-linked galactan, attached to O-4 of the rhamnosyl residues. 27441255 4 48 theme rhamnogalacturonan 760:777 arg1 RG-I 782:785 The rhamnogalacturonan I (RG-I) are 756:790 The rhamnogalacturonan I (RG-I) are 756:790 The rhamnogalacturonan I (RG-I) are consisted of a disaccharide repeating unit [→ α-D-GalpA-1,2-α-L-Rhap-1,4 →] backbone, with side chains contained highly branched α-(1 → 5)-linked arabinan and short linear β-(1 → 4)-linked galactan, attached to O-4 of the rhamnosyl residues. 27441255 1 49 theme Algeria 213:219 arg1 coast 195:199 the west coast 186:199 the west coast of northern Algeria 186:219 The pectin polysaccharides from leaves of Argania spinosa (L.) Skeels, collected from Stidia area in the west coast of northern Algeria, were investigated by using sequential extractions and the resulting fractions were analysed for monosaccharide composition and chemical structure. 29101656 6 0 theme microbial 1456:1464 arg1 component 1466:1474 a microbial component 1454:1474 a microbial component that is associated with increased mucosal permeability of the gut 1454:1540 Other skeletal diseases, such as bacterial chondronecrosis with osteomyelitis and enterococcal spondylitis, have a microbial component that is associated with increased mucosal permeability of the gut. 29101656 4 1 theme non-starch 851:860 arg1 NSP 879:881 NSP 879:881 NSP 879:881 Consumption of diets with a high content of soluble non-starch polysaccharides (NSP) can affect bone quality parameters by reducing the amount of conjugated bile acids in the intestine, therefore diminishing the absorption of fat-soluble vitamins such as vitamin D and minerals like calcium and phosphorus. 29101656 4 1 theme non-starch 851:860 arg1 polysaccharides 862:876 soluble non-starch polysaccharides 843:876 soluble non-starch polysaccharides (NSP) 843:882 Consumption of diets with a high content of soluble non-starch polysaccharides (NSP) can affect bone quality parameters by reducing the amount of conjugated bile acids in the intestine, therefore diminishing the absorption of fat-soluble vitamins such as vitamin D and minerals like calcium and phosphorus. 29101656 4 2 theme fat-soluble 1025:1035 arg1 vitamins 1037:1044 fat-soluble vitamins 1025:1044 fat-soluble vitamins such as vitamin D 1025:1062 Consumption of diets with a high content of soluble non-starch polysaccharides (NSP) can affect bone quality parameters by reducing the amount of conjugated bile acids in the intestine, therefore diminishing the absorption of fat-soluble vitamins such as vitamin D and minerals like calcium and phosphorus. 29101656 4 2 theme fat-soluble 1025:1035 arg1 D 1062:1062 vitamin D 1054:1062 vitamin D 1054:1062 Consumption of diets with a high content of soluble non-starch polysaccharides (NSP) can affect bone quality parameters by reducing the amount of conjugated bile acids in the intestine, therefore diminishing the absorption of fat-soluble vitamins such as vitamin D and minerals like calcium and phosphorus. 29101656 3 3 theme significant 700:710 arg1 impact 712:717 a significant impact 698:717 a significant impact on gut health, intestinal microbiota, bone quality, and performance parameters 698:796 For poultry, ingredients selected for feed formulation have also a significant impact on gut health, intestinal microbiota, bone quality, and performance parameters. 29101656 1 4 theme gut 275:277 arg1 cells 286:290 gut immune cells 275:290 gut immune cells 275:290 Intestinal barrier leakage and/or altered gut microbial composition has been shown to markedly impact both osteoblast and osteoclast activities, systemically through circulation of gut immune cells and cytokines and locally by causing inflammation of extraintestinal organs such as the liver and bone marrow. 29101656 5 5 contain have 1184:1187 arg1 diets 1178:1182 high NSP-containing diets 1158:1182 high NSP-containing diets 1158:1182 Recent enteric inflammation studies have shown that high NSP-containing diets have effects on intestinal viscosity, bone mineral content, and breaking strength, along with increased fluorescein isothiocyanate-dextran (FITC-d) leakage. 29101656 5 5 contain have 1184:1187 arg2 effects 1189:1195 effects 1189:1195 effects on intestinal viscosity, bone mineral content, and breaking strength 1189:1264 Recent enteric inflammation studies have shown that high NSP-containing diets have effects on intestinal viscosity, bone mineral content, and breaking strength, along with increased fluorescein isothiocyanate-dextran (FITC-d) leakage. 29101656 2 6 theme loss 548:551 arg1 absence 492:498 the absence 488:498 the absence 488:498 Mild cases of heightened intestinal inflammation can cause bone loss in male mice in the absence of any overt nutritional deficiencies or weight loss, which has also been shown in chickens that have been infected with Salmonella. 29101656 3 7 from impact 712:717 arg1 health 726:731 gut health 722:731 gut health 722:731 For poultry, ingredients selected for feed formulation have also a significant impact on gut health, intestinal microbiota, bone quality, and performance parameters. 29101656 3 7 from impact 712:717 arg1 microbiota 745:754 intestinal microbiota 734:754 intestinal microbiota 734:754 For poultry, ingredients selected for feed formulation have also a significant impact on gut health, intestinal microbiota, bone quality, and performance parameters. 29101656 3 7 from impact 712:717 arg1 quality 762:768 bone quality 757:768 bone quality 757:768 For poultry, ingredients selected for feed formulation have also a significant impact on gut health, intestinal microbiota, bone quality, and performance parameters. 29101656 3 7 from impact 712:717 arg1 parameters 787:796 performance parameters 775:796 performance parameters 775:796 For poultry, ingredients selected for feed formulation have also a significant impact on gut health, intestinal microbiota, bone quality, and performance parameters. 29101656 4 8 theme quality 900:906 arg1 parameters 908:917 bone quality parameters 895:917 bone quality parameters 895:917 Consumption of diets with a high content of soluble non-starch polysaccharides (NSP) can affect bone quality parameters by reducing the amount of conjugated bile acids in the intestine, therefore diminishing the absorption of fat-soluble vitamins such as vitamin D and minerals like calcium and phosphorus. 29101656 3 9 theme intestinal 734:743 arg1 microbiota 745:754 intestinal microbiota 734:754 intestinal microbiota 734:754 For poultry, ingredients selected for feed formulation have also a significant impact on gut health, intestinal microbiota, bone quality, and performance parameters. 29101656 5 10 theme enteric 1113:1119 arg1 studies 1134:1140 Recent enteric inflammation studies 1106:1140 Recent enteric inflammation studies 1106:1140 Recent enteric inflammation studies have shown that high NSP-containing diets have effects on intestinal viscosity, bone mineral content, and breaking strength, along with increased fluorescein isothiocyanate-dextran (FITC-d) leakage. 29101656 7 11 theme infectious 1626:1635 arg1 disease 1637:1643 infectious disease 1626:1643 infectious disease 1626:1643 Probiotics targeted toward control of enteric inflammation, either created through infectious disease or poor diet, may serve as a strategy for control of predisposing factors that lead to bone disorders. 29101656 7 12 dep targeted 1554:1561 arg1 either 1603:1608 either 1603:1608 either 1603:1608 Probiotics targeted toward control of enteric inflammation, either created through infectious disease or poor diet, may serve as a strategy for control of predisposing factors that lead to bone disorders. 29101656 1 13 theme altered 128:134 arg1 composition 150:160 altered gut microbial composition 128:160 altered gut microbial composition 128:160 Intestinal barrier leakage and/or altered gut microbial composition has been shown to markedly impact both osteoblast and osteoclast activities, systemically through circulation of gut immune cells and cytokines and locally by causing inflammation of extraintestinal organs such as the liver and bone marrow. 29101656 7 14 theme bone 1732:1735 arg1 disorders 1737:1745 bone disorders 1732:1745 bone disorders 1732:1745 Probiotics targeted toward control of enteric inflammation, either created through infectious disease or poor diet, may serve as a strategy for control of predisposing factors that lead to bone disorders. 29101656 0 15 theme Skeletal 53:60 arg1 Health 62:67 Skeletal Health 53:67 Skeletal Health 53:67 Impact of Enteric Health and Mucosal Permeability on Skeletal Health and Lameness in Poultry. 29101656 0 16 theme Enteric 10:16 arg1 Health 18:23 Enteric Health 10:23 Enteric Health 10:23 Impact of Enteric Health and Mucosal Permeability on Skeletal Health and Lameness in Poultry. 29101656 1 17 theme microbial 140:148 arg1 composition 150:160 altered gut microbial composition 128:160 altered gut microbial composition 128:160 Intestinal barrier leakage and/or altered gut microbial composition has been shown to markedly impact both osteoblast and osteoclast activities, systemically through circulation of gut immune cells and cytokines and locally by causing inflammation of extraintestinal organs such as the liver and bone marrow. 29101656 4 18 theme bile 956:959 arg1 acids 961:965 conjugated bile acids 945:965 conjugated bile acids in the intestine 945:982 Consumption of diets with a high content of soluble non-starch polysaccharides (NSP) can affect bone quality parameters by reducing the amount of conjugated bile acids in the intestine, therefore diminishing the absorption of fat-soluble vitamins such as vitamin D and minerals like calcium and phosphorus. 29101656 3 19 contain have 688:691 arg2 impact 712:717 a significant impact 698:717 a significant impact on gut health, intestinal microbiota, bone quality, and performance parameters 698:796 For poultry, ingredients selected for feed formulation have also a significant impact on gut health, intestinal microbiota, bone quality, and performance parameters. 29101656 3 19 contain have 688:691 arg1 ingredients 646:656 ingredients 646:656 ingredients selected for feed formulation 646:686 For poultry, ingredients selected for feed formulation have also a significant impact on gut health, intestinal microbiota, bone quality, and performance parameters. 29101656 1 20 theme extraintestinal 345:359 arg1 marrow 395:400 bone marrow 390:400 bone marrow 390:400 Intestinal barrier leakage and/or altered gut microbial composition has been shown to markedly impact both osteoblast and osteoclast activities, systemically through circulation of gut immune cells and cytokines and locally by causing inflammation of extraintestinal organs such as the liver and bone marrow. 29101656 1 20 theme extraintestinal 345:359 arg1 organs 361:366 extraintestinal organs 345:366 extraintestinal organs such as the liver and bone marrow 345:400 Intestinal barrier leakage and/or altered gut microbial composition has been shown to markedly impact both osteoblast and osteoclast activities, systemically through circulation of gut immune cells and cytokines and locally by causing inflammation of extraintestinal organs such as the liver and bone marrow. 29101656 1 20 theme extraintestinal 345:359 arg1 liver 380:384 liver 380:384 liver 380:384 Intestinal barrier leakage and/or altered gut microbial composition has been shown to markedly impact both osteoblast and osteoclast activities, systemically through circulation of gut immune cells and cytokines and locally by causing inflammation of extraintestinal organs such as the liver and bone marrow. 29101656 7 21 theme factors 1711:1717 arg1 control 1687:1693 control 1687:1693 control of predisposing factors that lead to bone disorders 1687:1745 Probiotics targeted toward control of enteric inflammation, either created through infectious disease or poor diet, may serve as a strategy for control of predisposing factors that lead to bone disorders. 29101656 7 22 theme enteric 1581:1587 arg1 inflammation 1589:1600 enteric inflammation 1581:1600 enteric inflammation 1581:1600 Probiotics targeted toward control of enteric inflammation, either created through infectious disease or poor diet, may serve as a strategy for control of predisposing factors that lead to bone disorders. 29101656 2 23 theme nutritional 513:523 arg1 deficiencies 525:536 any overt nutritional deficiencies 503:536 any overt nutritional deficiencies 503:536 Mild cases of heightened intestinal inflammation can cause bone loss in male mice in the absence of any overt nutritional deficiencies or weight loss, which has also been shown in chickens that have been infected with Salmonella. 29101656 0 24 from Impact 0:5 arg1 Lameness 73:80 Lameness 73:80 Lameness 73:80 Impact of Enteric Health and Mucosal Permeability on Skeletal Health and Lameness in Poultry. 29101656 0 24 from Impact 0:5 arg1 Health 62:67 Skeletal Health 53:67 Skeletal Health 53:67 Impact of Enteric Health and Mucosal Permeability on Skeletal Health and Lameness in Poultry. 29101656 6 25 theme skeletal 1347:1354 arg1 chondronecrosis 1384:1398 bacterial chondronecrosis 1374:1398 bacterial chondronecrosis with osteomyelitis and enterococcal spondylitis 1374:1446 Other skeletal diseases, such as bacterial chondronecrosis with osteomyelitis and enterococcal spondylitis, have a microbial component that is associated with increased mucosal permeability of the gut. 29101656 6 25 theme skeletal 1347:1354 arg1 diseases 1356:1363 Other skeletal diseases 1341:1363 Other skeletal diseases 1341:1363 Other skeletal diseases, such as bacterial chondronecrosis with osteomyelitis and enterococcal spondylitis, have a microbial component that is associated with increased mucosal permeability of the gut. 29101656 5 26 theme NSP-containing 1163:1176 arg1 diets 1178:1182 high NSP-containing diets 1158:1182 high NSP-containing diets 1158:1182 Recent enteric inflammation studies have shown that high NSP-containing diets have effects on intestinal viscosity, bone mineral content, and breaking strength, along with increased fluorescein isothiocyanate-dextran (FITC-d) leakage. 29101656 1 27 theme immune 279:284 arg1 cells 286:290 gut immune cells 275:290 gut immune cells 275:290 Intestinal barrier leakage and/or altered gut microbial composition has been shown to markedly impact both osteoblast and osteoclast activities, systemically through circulation of gut immune cells and cytokines and locally by causing inflammation of extraintestinal organs such as the liver and bone marrow. 29101656 2 28 theme inflammation 439:450 arg1 cases 408:412 Mild cases 403:412 Mild cases of heightened intestinal inflammation 403:450 Mild cases of heightened intestinal inflammation can cause bone loss in male mice in the absence of any overt nutritional deficiencies or weight loss, which has also been shown in chickens that have been infected with Salmonella. 29101656 5 29 theme increased 1278:1286 arg1 leakage 1332:1338 increased fluorescein isothiocyanate-dextran (FITC-d) leakage 1278:1338 increased fluorescein isothiocyanate-dextran (FITC-d) leakage 1278:1338 Recent enteric inflammation studies have shown that high NSP-containing diets have effects on intestinal viscosity, bone mineral content, and breaking strength, along with increased fluorescein isothiocyanate-dextran (FITC-d) leakage. 29101656 2 30 theme heightened 417:426 arg1 inflammation 439:450 heightened intestinal inflammation 417:450 heightened intestinal inflammation 417:450 Mild cases of heightened intestinal inflammation can cause bone loss in male mice in the absence of any overt nutritional deficiencies or weight loss, which has also been shown in chickens that have been infected with Salmonella. 29101656 6 31 theme enterococcal 1423:1434 arg1 spondylitis 1436:1446 enterococcal spondylitis 1423:1446 enterococcal spondylitis 1423:1446 Other skeletal diseases, such as bacterial chondronecrosis with osteomyelitis and enterococcal spondylitis, have a microbial component that is associated with increased mucosal permeability of the gut. 29101656 5 32 theme high 1158:1161 arg1 diets 1178:1182 high NSP-containing diets 1158:1182 high NSP-containing diets 1158:1182 Recent enteric inflammation studies have shown that high NSP-containing diets have effects on intestinal viscosity, bone mineral content, and breaking strength, along with increased fluorescein isothiocyanate-dextran (FITC-d) leakage. 29101656 1 33 theme Intestinal 94:103 arg1 leakage 113:119 Intestinal barrier leakage 94:119 Intestinal barrier leakage 94:119 Intestinal barrier leakage and/or altered gut microbial composition has been shown to markedly impact both osteoblast and osteoclast activities, systemically through circulation of gut immune cells and cytokines and locally by causing inflammation of extraintestinal organs such as the liver and bone marrow. 29101656 2 34 theme male 475:478 arg1 mice 480:483 male mice 475:483 male mice 475:483 Mild cases of heightened intestinal inflammation can cause bone loss in male mice in the absence of any overt nutritional deficiencies or weight loss, which has also been shown in chickens that have been infected with Salmonella. 29101656 5 35 theme isothiocyanate-dextran 1300:1321 arg1 leakage 1332:1338 increased fluorescein isothiocyanate-dextran (FITC-d) leakage 1278:1338 increased fluorescein isothiocyanate-dextran (FITC-d) leakage 1278:1338 Recent enteric inflammation studies have shown that high NSP-containing diets have effects on intestinal viscosity, bone mineral content, and breaking strength, along with increased fluorescein isothiocyanate-dextran (FITC-d) leakage. 29101656 4 36 from intestine 974:982 arg1 acids 961:965 conjugated bile acids 945:965 conjugated bile acids in the intestine 945:982 Consumption of diets with a high content of soluble non-starch polysaccharides (NSP) can affect bone quality parameters by reducing the amount of conjugated bile acids in the intestine, therefore diminishing the absorption of fat-soluble vitamins such as vitamin D and minerals like calcium and phosphorus. 29101656 4 36 from intestine 974:982 arg1 amount 935:940 the amount 931:940 the amount of conjugated bile acids in the intestine 931:982 Consumption of diets with a high content of soluble non-starch polysaccharides (NSP) can affect bone quality parameters by reducing the amount of conjugated bile acids in the intestine, therefore diminishing the absorption of fat-soluble vitamins such as vitamin D and minerals like calcium and phosphorus. 29101656 1 37 dep liver 380:384 arg1 the 376:378 the 376:378 the 376:378 Intestinal barrier leakage and/or altered gut microbial composition has been shown to markedly impact both osteoblast and osteoclast activities, systemically through circulation of gut immune cells and cytokines and locally by causing inflammation of extraintestinal organs such as the liver and bone marrow. 29101656 0 38 theme Permeability 37:48 arg1 Impact 0:5 Impact 0:5 Impact of Enteric Health and Mucosal Permeability on Skeletal Health and Lameness in Poultry. 0:92 Impact of Enteric Health and Mucosal Permeability on Skeletal Health and Lameness in Poultry. 29101656 5 39 theme intestinal 1200:1209 arg1 viscosity 1211:1219 intestinal viscosity 1200:1219 intestinal viscosity 1200:1219 Recent enteric inflammation studies have shown that high NSP-containing diets have effects on intestinal viscosity, bone mineral content, and breaking strength, along with increased fluorescein isothiocyanate-dextran (FITC-d) leakage. 29101656 1 40 dep impact 189:194 arg1 both 196:199 both 196:199 both 196:199 Intestinal barrier leakage and/or altered gut microbial composition has been shown to markedly impact both osteoblast and osteoclast activities, systemically through circulation of gut immune cells and cytokines and locally by causing inflammation of extraintestinal organs such as the liver and bone marrow. 29101656 7 41 dep Probiotics 1543:1552 arg1 targeted 1554:1561 targeted 1554:1561 targeted toward control of enteric inflammation 1554:1600 Probiotics targeted toward control of enteric inflammation, either created through infectious disease or poor diet, may serve as a strategy for control of predisposing factors that lead to bone disorders. 29101656 4 42 theme high 827:830 arg1 content 832:838 a high content 825:838 a high content of soluble non-starch polysaccharides (NSP) 825:882 Consumption of diets with a high content of soluble non-starch polysaccharides (NSP) can affect bone quality parameters by reducing the amount of conjugated bile acids in the intestine, therefore diminishing the absorption of fat-soluble vitamins such as vitamin D and minerals like calcium and phosphorus. 29101656 4 43 theme vitamins 1037:1044 arg1 absorption 1011:1020 the absorption 1007:1020 the absorption of fat-soluble vitamins such as vitamin D and minerals like calcium and phosphorus 1007:1103 Consumption of diets with a high content of soluble non-starch polysaccharides (NSP) can affect bone quality parameters by reducing the amount of conjugated bile acids in the intestine, therefore diminishing the absorption of fat-soluble vitamins such as vitamin D and minerals like calcium and phosphorus. 29101656 3 44 theme feed 671:674 arg1 formulation 676:686 feed formulation 671:686 feed formulation 671:686 For poultry, ingredients selected for feed formulation have also a significant impact on gut health, intestinal microbiota, bone quality, and performance parameters. 29101656 4 45 theme soluble 843:849 arg1 NSP 879:881 NSP 879:881 NSP 879:881 Consumption of diets with a high content of soluble non-starch polysaccharides (NSP) can affect bone quality parameters by reducing the amount of conjugated bile acids in the intestine, therefore diminishing the absorption of fat-soluble vitamins such as vitamin D and minerals like calcium and phosphorus. 29101656 4 45 theme soluble 843:849 arg1 polysaccharides 862:876 soluble non-starch polysaccharides 843:876 soluble non-starch polysaccharides (NSP) 843:882 Consumption of diets with a high content of soluble non-starch polysaccharides (NSP) can affect bone quality parameters by reducing the amount of conjugated bile acids in the intestine, therefore diminishing the absorption of fat-soluble vitamins such as vitamin D and minerals like calcium and phosphorus. 29101656 2 46 theme bone 462:465 arg1 loss 467:470 bone loss 462:470 bone loss 462:470 Mild cases of heightened intestinal inflammation can cause bone loss in male mice in the absence of any overt nutritional deficiencies or weight loss, which has also been shown in chickens that have been infected with Salmonella. 29101656 4 47 theme diets 814:818 arg1 Consumption 799:809 Consumption 799:809 Consumption of diets with a high content of soluble non-starch polysaccharides (NSP) 799:882 Consumption of diets with a high content of soluble non-starch polysaccharides (NSP) can affect bone quality parameters by reducing the amount of conjugated bile acids in the intestine, therefore diminishing the absorption of fat-soluble vitamins such as vitamin D and minerals like calcium and phosphorus. 29101656 6 48 theme gut 1538:1540 arg1 permeability 1518:1529 increased mucosal permeability 1500:1529 increased mucosal permeability of the gut 1500:1540 Other skeletal diseases, such as bacterial chondronecrosis with osteomyelitis and enterococcal spondylitis, have a microbial component that is associated with increased mucosal permeability of the gut. 29101656 4 49 theme minerals 1068:1075 arg1 absorption 1011:1020 the absorption 1007:1020 the absorption of fat-soluble vitamins such as vitamin D and minerals like calcium and phosphorus 1007:1103 Consumption of diets with a high content of soluble non-starch polysaccharides (NSP) can affect bone quality parameters by reducing the amount of conjugated bile acids in the intestine, therefore diminishing the absorption of fat-soluble vitamins such as vitamin D and minerals like calcium and phosphorus. 29101656 5 50 from effects 1189:1195 arg1 strength 1257:1264 breaking strength 1248:1264 breaking strength 1248:1264 Recent enteric inflammation studies have shown that high NSP-containing diets have effects on intestinal viscosity, bone mineral content, and breaking strength, along with increased fluorescein isothiocyanate-dextran (FITC-d) leakage. 29101656 5 50 from effects 1189:1195 arg1 content 1235:1241 bone mineral content 1222:1241 bone mineral content 1222:1241 Recent enteric inflammation studies have shown that high NSP-containing diets have effects on intestinal viscosity, bone mineral content, and breaking strength, along with increased fluorescein isothiocyanate-dextran (FITC-d) leakage. 29101656 5 50 from effects 1189:1195 arg1 viscosity 1211:1219 intestinal viscosity 1200:1219 intestinal viscosity 1200:1219 Recent enteric inflammation studies have shown that high NSP-containing diets have effects on intestinal viscosity, bone mineral content, and breaking strength, along with increased fluorescein isothiocyanate-dextran (FITC-d) leakage. 29101656 7 51 theme poor 1648:1651 arg1 diet 1653:1656 poor diet 1648:1656 poor diet 1648:1656 Probiotics targeted toward control of enteric inflammation, either created through infectious disease or poor diet, may serve as a strategy for control of predisposing factors that lead to bone disorders. 29101656 2 52 theme weight 541:546 arg1 loss 548:551 weight loss 541:551 weight loss 541:551 Mild cases of heightened intestinal inflammation can cause bone loss in male mice in the absence of any overt nutritional deficiencies or weight loss, which has also been shown in chickens that have been infected with Salmonella. 29101656 0 53 from Lameness 73:80 arg1 Poultry 85:91 Poultry 85:91 Poultry 85:91 Impact of Enteric Health and Mucosal Permeability on Skeletal Health and Lameness in Poultry. 29101656 3 54 theme gut 722:724 arg1 health 726:731 gut health 722:731 gut health 722:731 For poultry, ingredients selected for feed formulation have also a significant impact on gut health, intestinal microbiota, bone quality, and performance parameters. 29101656 1 55 theme bone 390:393 arg1 marrow 395:400 bone marrow 390:400 bone marrow 390:400 Intestinal barrier leakage and/or altered gut microbial composition has been shown to markedly impact both osteoblast and osteoclast activities, systemically through circulation of gut immune cells and cytokines and locally by causing inflammation of extraintestinal organs such as the liver and bone marrow. 29101656 6 56 theme mucosal 1510:1516 arg1 permeability 1518:1529 increased mucosal permeability 1500:1529 increased mucosal permeability of the gut 1500:1540 Other skeletal diseases, such as bacterial chondronecrosis with osteomyelitis and enterococcal spondylitis, have a microbial component that is associated with increased mucosal permeability of the gut. 29101656 1 57 theme osteoblast 201:210 arg1 activities 227:236 osteoblast and osteoclast activities 201:236 osteoblast and osteoclast activities 201:236 Intestinal barrier leakage and/or altered gut microbial composition has been shown to markedly impact both osteoblast and osteoclast activities, systemically through circulation of gut immune cells and cytokines and locally by causing inflammation of extraintestinal organs such as the liver and bone marrow. 29101656 4 58 theme bone 895:898 arg1 parameters 908:917 bone quality parameters 895:917 bone quality parameters 895:917 Consumption of diets with a high content of soluble non-starch polysaccharides (NSP) can affect bone quality parameters by reducing the amount of conjugated bile acids in the intestine, therefore diminishing the absorption of fat-soluble vitamins such as vitamin D and minerals like calcium and phosphorus. 29101656 0 59 from Health 62:67 arg1 Poultry 85:91 Poultry 85:91 Poultry 85:91 Impact of Enteric Health and Mucosal Permeability on Skeletal Health and Lameness in Poultry. 29101656 3 60 theme bone 757:760 arg1 quality 762:768 bone quality 757:768 bone quality 757:768 For poultry, ingredients selected for feed formulation have also a significant impact on gut health, intestinal microbiota, bone quality, and performance parameters. 29101656 1 61 theme barrier 105:111 arg1 leakage 113:119 Intestinal barrier leakage 94:119 Intestinal barrier leakage 94:119 Intestinal barrier leakage and/or altered gut microbial composition has been shown to markedly impact both osteoblast and osteoclast activities, systemically through circulation of gut immune cells and cytokines and locally by causing inflammation of extraintestinal organs such as the liver and bone marrow. 29101656 5 62 theme Recent 1106:1111 arg1 studies 1134:1140 Recent enteric inflammation studies 1106:1140 Recent enteric inflammation studies 1106:1140 Recent enteric inflammation studies have shown that high NSP-containing diets have effects on intestinal viscosity, bone mineral content, and breaking strength, along with increased fluorescein isothiocyanate-dextran (FITC-d) leakage. 29101656 4 63 theme polysaccharides 862:876 arg1 content 832:838 a high content 825:838 a high content of soluble non-starch polysaccharides (NSP) 825:882 Consumption of diets with a high content of soluble non-starch polysaccharides (NSP) can affect bone quality parameters by reducing the amount of conjugated bile acids in the intestine, therefore diminishing the absorption of fat-soluble vitamins such as vitamin D and minerals like calcium and phosphorus. 29101656 5 64 theme breaking 1248:1255 arg1 strength 1257:1264 breaking strength 1248:1264 breaking strength 1248:1264 Recent enteric inflammation studies have shown that high NSP-containing diets have effects on intestinal viscosity, bone mineral content, and breaking strength, along with increased fluorescein isothiocyanate-dextran (FITC-d) leakage. 29101656 3 65 theme performance 775:785 arg1 parameters 787:796 performance parameters 775:796 performance parameters 775:796 For poultry, ingredients selected for feed formulation have also a significant impact on gut health, intestinal microbiota, bone quality, and performance parameters. 29101656 6 66 theme bacterial 1374:1382 arg1 chondronecrosis 1384:1398 bacterial chondronecrosis 1374:1398 bacterial chondronecrosis with osteomyelitis and enterococcal spondylitis 1374:1446 Other skeletal diseases, such as bacterial chondronecrosis with osteomyelitis and enterococcal spondylitis, have a microbial component that is associated with increased mucosal permeability of the gut. 29101656 1 67 theme gut 136:138 arg1 composition 150:160 altered gut microbial composition 128:160 altered gut microbial composition 128:160 Intestinal barrier leakage and/or altered gut microbial composition has been shown to markedly impact both osteoblast and osteoclast activities, systemically through circulation of gut immune cells and cytokines and locally by causing inflammation of extraintestinal organs such as the liver and bone marrow. 29101656 7 68 theme inflammation 1589:1600 arg1 control 1570:1576 control 1570:1576 control of enteric inflammation 1570:1600 Probiotics targeted toward control of enteric inflammation, either created through infectious disease or poor diet, may serve as a strategy for control of predisposing factors that lead to bone disorders. 29101656 1 69 theme osteoclast 216:225 arg1 activities 227:236 osteoblast and osteoclast activities 201:236 osteoblast and osteoclast activities 201:236 Intestinal barrier leakage and/or altered gut microbial composition has been shown to markedly impact both osteoblast and osteoclast activities, systemically through circulation of gut immune cells and cytokines and locally by causing inflammation of extraintestinal organs such as the liver and bone marrow. 29101656 5 70 theme mineral 1227:1233 arg1 content 1235:1241 bone mineral content 1222:1241 bone mineral content 1222:1241 Recent enteric inflammation studies have shown that high NSP-containing diets have effects on intestinal viscosity, bone mineral content, and breaking strength, along with increased fluorescein isothiocyanate-dextran (FITC-d) leakage. 29101656 4 71 theme conjugated 945:954 arg1 acids 961:965 conjugated bile acids 945:965 conjugated bile acids in the intestine 945:982 Consumption of diets with a high content of soluble non-starch polysaccharides (NSP) can affect bone quality parameters by reducing the amount of conjugated bile acids in the intestine, therefore diminishing the absorption of fat-soluble vitamins such as vitamin D and minerals like calcium and phosphorus. 29101656 1 72 theme organs 361:366 arg1 inflammation 329:340 inflammation 329:340 inflammation of extraintestinal organs such as the liver and bone marrow 329:400 Intestinal barrier leakage and/or altered gut microbial composition has been shown to markedly impact both osteoblast and osteoclast activities, systemically through circulation of gut immune cells and cytokines and locally by causing inflammation of extraintestinal organs such as the liver and bone marrow. 29101656 4 73 with diets 814:818 arg1 content 832:838 a high content 825:838 a high content of soluble non-starch polysaccharides (NSP) 825:882 Consumption of diets with a high content of soluble non-starch polysaccharides (NSP) can affect bone quality parameters by reducing the amount of conjugated bile acids in the intestine, therefore diminishing the absorption of fat-soluble vitamins such as vitamin D and minerals like calcium and phosphorus. 29101656 2 74 theme overt 507:511 arg1 deficiencies 525:536 any overt nutritional deficiencies 503:536 any overt nutritional deficiencies 503:536 Mild cases of heightened intestinal inflammation can cause bone loss in male mice in the absence of any overt nutritional deficiencies or weight loss, which has also been shown in chickens that have been infected with Salmonella. 29101656 6 75 theme Other 1341:1345 arg1 chondronecrosis 1384:1398 bacterial chondronecrosis 1374:1398 bacterial chondronecrosis with osteomyelitis and enterococcal spondylitis 1374:1446 Other skeletal diseases, such as bacterial chondronecrosis with osteomyelitis and enterococcal spondylitis, have a microbial component that is associated with increased mucosal permeability of the gut. 29101656 6 75 theme Other 1341:1345 arg1 diseases 1356:1363 Other skeletal diseases 1341:1363 Other skeletal diseases 1341:1363 Other skeletal diseases, such as bacterial chondronecrosis with osteomyelitis and enterococcal spondylitis, have a microbial component that is associated with increased mucosal permeability of the gut. 29101656 7 76 theme predisposing 1698:1709 arg1 factors 1711:1717 predisposing factors 1698:1717 predisposing factors that lead to bone disorders 1698:1745 Probiotics targeted toward control of enteric inflammation, either created through infectious disease or poor diet, may serve as a strategy for control of predisposing factors that lead to bone disorders. 29101656 6 77 with chondronecrosis 1384:1398 arg1 osteomyelitis 1405:1417 osteomyelitis 1405:1417 osteomyelitis 1405:1417 Other skeletal diseases, such as bacterial chondronecrosis with osteomyelitis and enterococcal spondylitis, have a microbial component that is associated with increased mucosal permeability of the gut. 29101656 6 77 with chondronecrosis 1384:1398 arg1 spondylitis 1436:1446 enterococcal spondylitis 1423:1446 enterococcal spondylitis 1423:1446 Other skeletal diseases, such as bacterial chondronecrosis with osteomyelitis and enterococcal spondylitis, have a microbial component that is associated with increased mucosal permeability of the gut. 29101656 0 78 theme Health 18:23 arg1 Impact 0:5 Impact 0:5 Impact of Enteric Health and Mucosal Permeability on Skeletal Health and Lameness in Poultry. 0:92 Impact of Enteric Health and Mucosal Permeability on Skeletal Health and Lameness in Poultry. 29101656 1 79 theme cells 286:290 arg1 circulation 260:270 circulation 260:270 circulation of gut immune cells and cytokines 260:304 Intestinal barrier leakage and/or altered gut microbial composition has been shown to markedly impact both osteoblast and osteoclast activities, systemically through circulation of gut immune cells and cytokines and locally by causing inflammation of extraintestinal organs such as the liver and bone marrow. 29101656 2 80 theme intestinal 428:437 arg1 inflammation 439:450 heightened intestinal inflammation 417:450 heightened intestinal inflammation 417:450 Mild cases of heightened intestinal inflammation can cause bone loss in male mice in the absence of any overt nutritional deficiencies or weight loss, which has also been shown in chickens that have been infected with Salmonella. 29101656 5 81 theme fluorescein 1288:1298 arg1 FITC-d 1324:1329 FITC-d 1324:1329 FITC-d 1324:1329 Recent enteric inflammation studies have shown that high NSP-containing diets have effects on intestinal viscosity, bone mineral content, and breaking strength, along with increased fluorescein isothiocyanate-dextran (FITC-d) leakage. 29101656 5 81 theme fluorescein 1288:1298 arg1 isothiocyanate-dextran 1300:1321 fluorescein isothiocyanate-dextran 1288:1321 increased fluorescein isothiocyanate-dextran (FITC-d) leakage 1278:1338 Recent enteric inflammation studies have shown that high NSP-containing diets have effects on intestinal viscosity, bone mineral content, and breaking strength, along with increased fluorescein isothiocyanate-dextran (FITC-d) leakage. 29101656 0 82 theme Mucosal 29:35 arg1 Permeability 37:48 Mucosal Permeability 29:48 Mucosal Permeability 29:48 Impact of Enteric Health and Mucosal Permeability on Skeletal Health and Lameness in Poultry. 29101656 1 83 theme cytokines 296:304 arg1 circulation 260:270 circulation 260:270 circulation of gut immune cells and cytokines 260:304 Intestinal barrier leakage and/or altered gut microbial composition has been shown to markedly impact both osteoblast and osteoclast activities, systemically through circulation of gut immune cells and cytokines and locally by causing inflammation of extraintestinal organs such as the liver and bone marrow. 29101656 4 84 theme acids 961:965 arg1 acids 961:965 conjugated bile acids 945:965 conjugated bile acids in the intestine 945:982 Consumption of diets with a high content of soluble non-starch polysaccharides (NSP) can affect bone quality parameters by reducing the amount of conjugated bile acids in the intestine, therefore diminishing the absorption of fat-soluble vitamins such as vitamin D and minerals like calcium and phosphorus. 29101656 4 84 theme acids 961:965 arg1 amount 935:940 the amount 931:940 the amount of conjugated bile acids in the intestine 931:982 Consumption of diets with a high content of soluble non-starch polysaccharides (NSP) can affect bone quality parameters by reducing the amount of conjugated bile acids in the intestine, therefore diminishing the absorption of fat-soluble vitamins such as vitamin D and minerals like calcium and phosphorus. 29101656 2 85 theme Mild 403:406 arg1 cases 408:412 Mild cases 403:412 Mild cases of heightened intestinal inflammation 403:450 Mild cases of heightened intestinal inflammation can cause bone loss in male mice in the absence of any overt nutritional deficiencies or weight loss, which has also been shown in chickens that have been infected with Salmonella. 29101656 5 86 theme inflammation 1121:1132 arg1 studies 1134:1140 Recent enteric inflammation studies 1106:1140 Recent enteric inflammation studies 1106:1140 Recent enteric inflammation studies have shown that high NSP-containing diets have effects on intestinal viscosity, bone mineral content, and breaking strength, along with increased fluorescein isothiocyanate-dextran (FITC-d) leakage. 29101656 2 87 theme deficiencies 525:536 arg1 absence 492:498 the absence 488:498 the absence 488:498 Mild cases of heightened intestinal inflammation can cause bone loss in male mice in the absence of any overt nutritional deficiencies or weight loss, which has also been shown in chickens that have been infected with Salmonella. 29101656 6 88 theme increased 1500:1508 arg1 permeability 1518:1529 increased mucosal permeability 1500:1529 increased mucosal permeability of the gut 1500:1540 Other skeletal diseases, such as bacterial chondronecrosis with osteomyelitis and enterococcal spondylitis, have a microbial component that is associated with increased mucosal permeability of the gut. 29101656 4 89 from acids 961:965 arg1 intestine 974:982 the intestine 970:982 the intestine 970:982 Consumption of diets with a high content of soluble non-starch polysaccharides (NSP) can affect bone quality parameters by reducing the amount of conjugated bile acids in the intestine, therefore diminishing the absorption of fat-soluble vitamins such as vitamin D and minerals like calcium and phosphorus. 29101656 6 90 contain have 1449:1452 arg1 chondronecrosis 1384:1398 bacterial chondronecrosis 1374:1398 bacterial chondronecrosis with osteomyelitis and enterococcal spondylitis 1374:1446 Other skeletal diseases, such as bacterial chondronecrosis with osteomyelitis and enterococcal spondylitis, have a microbial component that is associated with increased mucosal permeability of the gut. 29101656 6 90 contain have 1449:1452 arg1 diseases 1356:1363 Other skeletal diseases 1341:1363 Other skeletal diseases 1341:1363 Other skeletal diseases, such as bacterial chondronecrosis with osteomyelitis and enterococcal spondylitis, have a microbial component that is associated with increased mucosal permeability of the gut. 29101656 6 90 contain have 1449:1452 arg2 component 1466:1474 a microbial component 1454:1474 a microbial component that is associated with increased mucosal permeability of the gut 1454:1540 Other skeletal diseases, such as bacterial chondronecrosis with osteomyelitis and enterococcal spondylitis, have a microbial component that is associated with increased mucosal permeability of the gut. 29101656 4 91 theme vitamin 1054:1060 arg1 D 1062:1062 vitamin D 1054:1062 vitamin D 1054:1062 Consumption of diets with a high content of soluble non-starch polysaccharides (NSP) can affect bone quality parameters by reducing the amount of conjugated bile acids in the intestine, therefore diminishing the absorption of fat-soluble vitamins such as vitamin D and minerals like calcium and phosphorus. 29101656 5 92 theme bone 1222:1225 arg1 content 1235:1241 bone mineral content 1222:1241 bone mineral content 1222:1241 Recent enteric inflammation studies have shown that high NSP-containing diets have effects on intestinal viscosity, bone mineral content, and breaking strength, along with increased fluorescein isothiocyanate-dextran (FITC-d) leakage. 29101656 4 93 from amount 935:940 arg1 intestine 974:982 the intestine 970:982 the intestine 970:982 Consumption of diets with a high content of soluble non-starch polysaccharides (NSP) can affect bone quality parameters by reducing the amount of conjugated bile acids in the intestine, therefore diminishing the absorption of fat-soluble vitamins such as vitamin D and minerals like calcium and phosphorus. 28597443 7 0 theme A. 1169:1170 arg1 cinnamomea 1172:1181 the regular A. cinnamomea 1157:1181 the regular A. cinnamomea from orange-red to white 1157:1206 CONCLUSIONS Blue-light radiation could change color of the regular A. cinnamomea from orange-red to white by changing its secondary metabolism and growth condition. 28597443 3 1 theme occurring 527:535 arg1 cinnamomea 569:578 naturally occurring and blue-light induced white A. cinnamomea 517:578 naturally occurring and blue-light induced white A. cinnamomea 517:578 Therefore it is of interest to study the chemical variation of regular orange-red strains and white strains, which included naturally occurring and blue-light induced white A. cinnamomea. 28597443 9 2 theme wild 1729:1732 arg1 culture 1747:1753 wild or submerged culture 1729:1753 wild or submerged culture 1729:1753 The ergostane-type triterpenoids were found existing in both young mycelia and old mycelia with fruiting body in artificial agar-plate medium culture, suggesting a more diversified biosynthetic pathway in artificial agar-plate culture rather than wild or submerged culture. 28597443 4 3 theme cinnamomea 617:626 arg1 extracts 628:635 A. cinnamomea extracts 614:635 A. cinnamomea extracts 614:635 RESULTS The chemical profiles of A. cinnamomea extracts at different growth stages were compared using thin layer chromatography (TLC) and high performance liquid chromatography (HPLC). 28597443 6 4 theme white 919:923 arg1 strain 925:930 blue-light induced white strain 900:930 blue-light induced white strain 900:930 Moreover, the compounds of blue-light induced white strain were similar to those of naturally occurring white strain but retained specific chemical characteristics in more polar region of the HPLC chromatogram of regular strain. 28597443 9 5 theme submerged 1737:1745 arg1 culture 1747:1753 wild or submerged culture 1729:1753 wild or submerged culture 1729:1753 The ergostane-type triterpenoids were found existing in both young mycelia and old mycelia with fruiting body in artificial agar-plate medium culture, suggesting a more diversified biosynthetic pathway in artificial agar-plate culture rather than wild or submerged culture. 28597443 4 6 theme layer 689:693 arg1 TLC 711:713 TLC 711:713 TLC 711:713 RESULTS The chemical profiles of A. cinnamomea extracts at different growth stages were compared using thin layer chromatography (TLC) and high performance liquid chromatography (HPLC). 28597443 4 6 theme layer 689:693 arg1 chromatography 695:708 thin layer chromatography 684:708 thin layer chromatography (TLC) 684:714 RESULTS The chemical profiles of A. cinnamomea extracts at different growth stages were compared using thin layer chromatography (TLC) and high performance liquid chromatography (HPLC). 28597443 3 7 theme white 560:564 arg1 cinnamomea 569:578 naturally occurring and blue-light induced white A. cinnamomea 517:578 naturally occurring and blue-light induced white A. cinnamomea 517:578 Therefore it is of interest to study the chemical variation of regular orange-red strains and white strains, which included naturally occurring and blue-light induced white A. cinnamomea. 28597443 9 8 theme ergostane-type 1486:1499 arg1 triterpenoids 1501:1513 The ergostane-type triterpenoids 1482:1513 The ergostane-type triterpenoids 1482:1513 The ergostane-type triterpenoids were found existing in both young mycelia and old mycelia with fruiting body in artificial agar-plate medium culture, suggesting a more diversified biosynthetic pathway in artificial agar-plate culture rather than wild or submerged culture. 28597443 6 9 theme blue-light 900:909 arg1 strain 925:930 blue-light induced white strain 900:930 blue-light induced white strain 900:930 Moreover, the compounds of blue-light induced white strain were similar to those of naturally occurring white strain but retained specific chemical characteristics in more polar region of the HPLC chromatogram of regular strain. 28597443 7 10 theme Blue-light 1114:1123 arg1 radiation 1125:1133 Blue-light radiation 1114:1133 Blue-light radiation 1114:1133 CONCLUSIONS Blue-light radiation could change color of the regular A. cinnamomea from orange-red to white by changing its secondary metabolism and growth condition. 28597443 2 11 theme medicinal 301:309 arg1 effects 311:317 medicinal effects 301:317 medicinal effects 301:317 Many studies have confirmed that A. cinnamomea is rich in polysaccharides and triterpenoids that may carry medicinal effects in anti-cancer, anti-inflammation, anti-hypertension, and anti-oxidation. 28597443 8 12 theme different 1329:1337 arg1 composition 1339:1349 a significantly different composition 1313:1349 a significantly different composition of triterpenoid profiles up to eight weeks old 1313:1396 Naturally occurring white strain did not show a significantly different composition of triterpenoid profiles up to eight weeks old when compared with the triterpenoid profiles of the regular strain at the same age. 28597443 5 13 theme white 846:850 arg1 strains 864:870 white and regular strains 846:870 white and regular strains 846:870 The TLC and HPLC profiles indicated that specific triterpenoids varied between white and regular strains. 28597443 8 14 theme occurring 1277:1285 arg1 strain 1293:1298 Naturally occurring white strain 1267:1298 Naturally occurring white strain 1267:1298 Naturally occurring white strain did not show a significantly different composition of triterpenoid profiles up to eight weeks old when compared with the triterpenoid profiles of the regular strain at the same age. 28597443 6 15 theme occurring 967:975 arg1 strain 983:988 naturally occurring white strain 957:988 naturally occurring white strain 957:988 Moreover, the compounds of blue-light induced white strain were similar to those of naturally occurring white strain but retained specific chemical characteristics in more polar region of the HPLC chromatogram of regular strain. 28597443 6 16 dep occurring 967:975 arg1 white 977:981 white 977:981 white 977:981 Moreover, the compounds of blue-light induced white strain were similar to those of naturally occurring white strain but retained specific chemical characteristics in more polar region of the HPLC chromatogram of regular strain. 28597443 4 17 theme liquid 737:742 arg1 HPLC 760:763 HPLC 760:763 HPLC 760:763 RESULTS The chemical profiles of A. cinnamomea extracts at different growth stages were compared using thin layer chromatography (TLC) and high performance liquid chromatography (HPLC). 28597443 4 17 theme liquid 737:742 arg1 chromatography 744:757 high performance liquid chromatography 720:757 high performance liquid chromatography (HPLC) 720:764 RESULTS The chemical profiles of A. cinnamomea extracts at different growth stages were compared using thin layer chromatography (TLC) and high performance liquid chromatography (HPLC). 28597443 1 18 theme host 125:128 arg1 kanehirae 141:149 its host Cinnamomum kanehirae 121:149 its host Cinnamomum kanehirae 121:149 BACKGROUND Antrodia cinnamomea and its host Cinnamomum kanehirae are both endemic species unique to Taiwan. 28597443 1 18 theme host 125:128 arg1 cinnamomea 106:115 BACKGROUND Antrodia cinnamomea 86:115 BACKGROUND Antrodia cinnamomea 86:115 BACKGROUND Antrodia cinnamomea and its host Cinnamomum kanehirae are both endemic species unique to Taiwan. 28597443 1 18 theme host 125:128 arg1 species 168:174 both endemic species 155:174 both endemic species unique to Taiwan 155:191 BACKGROUND Antrodia cinnamomea and its host Cinnamomum kanehirae are both endemic species unique to Taiwan. 28597443 8 19 theme profiles 1367:1374 arg1 composition 1339:1349 a significantly different composition 1313:1349 a significantly different composition of triterpenoid profiles up to eight weeks old 1313:1396 Naturally occurring white strain did not show a significantly different composition of triterpenoid profiles up to eight weeks old when compared with the triterpenoid profiles of the regular strain at the same age. 28597443 9 20 theme old 1561:1563 arg1 mycelia 1565:1571 old mycelia 1561:1571 old mycelia 1561:1571 The ergostane-type triterpenoids were found existing in both young mycelia and old mycelia with fruiting body in artificial agar-plate medium culture, suggesting a more diversified biosynthetic pathway in artificial agar-plate culture rather than wild or submerged culture. 28597443 0 21 theme white 59:63 arg1 cinnamomea 74:83 regular and white Antrodia cinnamomea 47:83 regular and white Antrodia cinnamomea 47:83 Phenologic variation of major triterpenoids in regular and white Antrodia cinnamomea. 28597443 6 22 theme polar 1045:1049 arg1 region 1051:1056 more polar region 1040:1056 more polar region of the HPLC chromatogram of regular strain 1040:1099 Moreover, the compounds of blue-light induced white strain were similar to those of naturally occurring white strain but retained specific chemical characteristics in more polar region of the HPLC chromatogram of regular strain. 28597443 7 23 dep white 1202:1206 arg1 to 1199:1200 to 1199:1200 to 1199:1200 CONCLUSIONS Blue-light radiation could change color of the regular A. cinnamomea from orange-red to white by changing its secondary metabolism and growth condition. 28597443 4 24 theme high 720:723 arg1 HPLC 760:763 HPLC 760:763 HPLC 760:763 RESULTS The chemical profiles of A. cinnamomea extracts at different growth stages were compared using thin layer chromatography (TLC) and high performance liquid chromatography (HPLC). 28597443 4 24 theme high 720:723 arg1 chromatography 744:757 high performance liquid chromatography 720:757 high performance liquid chromatography (HPLC) 720:764 RESULTS The chemical profiles of A. cinnamomea extracts at different growth stages were compared using thin layer chromatography (TLC) and high performance liquid chromatography (HPLC). 28597443 9 25 with mycelia 1565:1571 arg1 body 1587:1590 fruiting body 1578:1590 fruiting body 1578:1590 The ergostane-type triterpenoids were found existing in both young mycelia and old mycelia with fruiting body in artificial agar-plate medium culture, suggesting a more diversified biosynthetic pathway in artificial agar-plate culture rather than wild or submerged culture. 28597443 7 26 theme growth 1249:1254 arg1 condition 1256:1264 growth condition 1249:1264 growth condition 1249:1264 CONCLUSIONS Blue-light radiation could change color of the regular A. cinnamomea from orange-red to white by changing its secondary metabolism and growth condition. 28597443 9 27 theme artificial 1595:1604 arg1 culture 1624:1630 artificial agar-plate medium culture 1595:1630 artificial agar-plate medium culture 1595:1630 The ergostane-type triterpenoids were found existing in both young mycelia and old mycelia with fruiting body in artificial agar-plate medium culture, suggesting a more diversified biosynthetic pathway in artificial agar-plate culture rather than wild or submerged culture. 28597443 6 28 theme chemical 1012:1019 arg1 characteristics 1021:1035 specific chemical characteristics 1003:1035 specific chemical characteristics 1003:1035 Moreover, the compounds of blue-light induced white strain were similar to those of naturally occurring white strain but retained specific chemical characteristics in more polar region of the HPLC chromatogram of regular strain. 28597443 4 29 dep RESULTS 581:587 arg1 compared 669:676 compared 669:676 were compared using thin layer chromatography (TLC) and high performance liquid chromatography (HPLC) 664:764 RESULTS The chemical profiles of A. cinnamomea extracts at different growth stages were compared using thin layer chromatography (TLC) and high performance liquid chromatography (HPLC). 28597443 9 30 theme medium 1617:1622 arg1 culture 1624:1630 artificial agar-plate medium culture 1595:1630 artificial agar-plate medium culture 1595:1630 The ergostane-type triterpenoids were found existing in both young mycelia and old mycelia with fruiting body in artificial agar-plate medium culture, suggesting a more diversified biosynthetic pathway in artificial agar-plate culture rather than wild or submerged culture. 28597443 0 31 theme Antrodia 65:72 arg1 cinnamomea 74:83 regular and white Antrodia cinnamomea 47:83 regular and white Antrodia cinnamomea 47:83 Phenologic variation of major triterpenoids in regular and white Antrodia cinnamomea. 28597443 8 32 theme triterpenoid 1421:1432 arg1 profiles 1434:1441 the triterpenoid profiles 1417:1441 the triterpenoid profiles of the regular strain at the same age 1417:1479 Naturally occurring white strain did not show a significantly different composition of triterpenoid profiles up to eight weeks old when compared with the triterpenoid profiles of the regular strain at the same age. 28597443 3 33 theme chemical 434:441 arg1 variation 443:451 the chemical variation 430:451 the chemical variation of regular orange-red strains and white strains 430:499 Therefore it is of interest to study the chemical variation of regular orange-red strains and white strains, which included naturally occurring and blue-light induced white A. cinnamomea. 28597443 0 34 theme Phenologic 0:9 arg1 variation 11:19 Phenologic variation 0:19 Phenologic variation of major triterpenoids in regular and white Antrodia cinnamomea. 0:84 Phenologic variation of major triterpenoids in regular and white Antrodia cinnamomea. 28597443 1 35 theme Antrodia 97:104 arg1 kanehirae 141:149 its host Cinnamomum kanehirae 121:149 its host Cinnamomum kanehirae 121:149 BACKGROUND Antrodia cinnamomea and its host Cinnamomum kanehirae are both endemic species unique to Taiwan. 28597443 1 35 theme Antrodia 97:104 arg1 cinnamomea 106:115 BACKGROUND Antrodia cinnamomea 86:115 BACKGROUND Antrodia cinnamomea 86:115 BACKGROUND Antrodia cinnamomea and its host Cinnamomum kanehirae are both endemic species unique to Taiwan. 28597443 1 35 theme Antrodia 97:104 arg1 species 168:174 both endemic species 155:174 both endemic species unique to Taiwan 155:191 BACKGROUND Antrodia cinnamomea and its host Cinnamomum kanehirae are both endemic species unique to Taiwan. 28597443 6 36 theme strain 1094:1099 arg1 chromatogram 1070:1081 the HPLC chromatogram 1061:1081 the HPLC chromatogram of regular strain 1061:1099 Moreover, the compounds of blue-light induced white strain were similar to those of naturally occurring white strain but retained specific chemical characteristics in more polar region of the HPLC chromatogram of regular strain. 28597443 7 37 from color 1148:1152 arg1 white 1202:1206 white 1202:1206 white 1202:1206 CONCLUSIONS Blue-light radiation could change color of the regular A. cinnamomea from orange-red to white by changing its secondary metabolism and growth condition. 28597443 8 38 theme regular 1450:1456 arg1 strain 1458:1463 the regular strain 1446:1463 the regular strain 1446:1463 Naturally occurring white strain did not show a significantly different composition of triterpenoid profiles up to eight weeks old when compared with the triterpenoid profiles of the regular strain at the same age. 28597443 3 39 theme orange-red 464:473 arg1 strains 475:481 regular orange-red strains 456:481 regular orange-red strains 456:481 Therefore it is of interest to study the chemical variation of regular orange-red strains and white strains, which included naturally occurring and blue-light induced white A. cinnamomea. 28597443 0 40 theme triterpenoids 30:42 arg1 variation 11:19 Phenologic variation 0:19 Phenologic variation of major triterpenoids in regular and white Antrodia cinnamomea. 0:84 Phenologic variation of major triterpenoids in regular and white Antrodia cinnamomea. 28597443 8 41 dep eight 1382:1386 arg1 to 1379:1380 to 1379:1380 to 1379:1380 Naturally occurring white strain did not show a significantly different composition of triterpenoid profiles up to eight weeks old when compared with the triterpenoid profiles of the regular strain at the same age. 28597443 6 42 theme HPLC 1065:1068 arg1 chromatogram 1070:1081 the HPLC chromatogram 1061:1081 the HPLC chromatogram of regular strain 1061:1099 Moreover, the compounds of blue-light induced white strain were similar to those of naturally occurring white strain but retained specific chemical characteristics in more polar region of the HPLC chromatogram of regular strain. 28597443 0 43 theme regular 47:53 arg1 cinnamomea 74:83 regular and white Antrodia cinnamomea 47:83 regular and white Antrodia cinnamomea 47:83 Phenologic variation of major triterpenoids in regular and white Antrodia cinnamomea. 28597443 8 44 theme same 1472:1475 arg1 age 1477:1479 the same age 1468:1479 the same age 1468:1479 Naturally occurring white strain did not show a significantly different composition of triterpenoid profiles up to eight weeks old when compared with the triterpenoid profiles of the regular strain at the same age. 28597443 9 45 theme diversified 1651:1661 arg1 pathway 1676:1682 a more diversified biosynthetic pathway 1644:1682 a more diversified biosynthetic pathway in artificial agar-plate culture rather than wild or submerged culture 1644:1753 The ergostane-type triterpenoids were found existing in both young mycelia and old mycelia with fruiting body in artificial agar-plate medium culture, suggesting a more diversified biosynthetic pathway in artificial agar-plate culture rather than wild or submerged culture. 28597443 3 46 theme strains 493:499 arg1 variation 443:451 the chemical variation 430:451 the chemical variation of regular orange-red strains and white strains 430:499 Therefore it is of interest to study the chemical variation of regular orange-red strains and white strains, which included naturally occurring and blue-light induced white A. cinnamomea. 28597443 9 47 theme artificial 1687:1696 arg1 culture 1709:1715 artificial agar-plate culture 1687:1715 artificial agar-plate culture 1687:1715 The ergostane-type triterpenoids were found existing in both young mycelia and old mycelia with fruiting body in artificial agar-plate medium culture, suggesting a more diversified biosynthetic pathway in artificial agar-plate culture rather than wild or submerged culture. 28597443 4 48 theme extracts 628:635 arg1 profiles 602:609 The chemical profiles 589:609 The chemical profiles of A. cinnamomea extracts at different growth stages 589:662 RESULTS The chemical profiles of A. cinnamomea extracts at different growth stages were compared using thin layer chromatography (TLC) and high performance liquid chromatography (HPLC). 28597443 2 49 theme Many 194:197 arg1 studies 199:205 Many studies 194:205 Many studies 194:205 Many studies have confirmed that A. cinnamomea is rich in polysaccharides and triterpenoids that may carry medicinal effects in anti-cancer, anti-inflammation, anti-hypertension, and anti-oxidation. 28597443 4 50 theme thin 684:687 arg1 TLC 711:713 TLC 711:713 TLC 711:713 RESULTS The chemical profiles of A. cinnamomea extracts at different growth stages were compared using thin layer chromatography (TLC) and high performance liquid chromatography (HPLC). 28597443 4 50 theme thin 684:687 arg1 chromatography 695:708 thin layer chromatography 684:708 thin layer chromatography (TLC) 684:714 RESULTS The chemical profiles of A. cinnamomea extracts at different growth stages were compared using thin layer chromatography (TLC) and high performance liquid chromatography (HPLC). 28597443 5 51 theme specific 808:815 arg1 triterpenoids 817:829 specific triterpenoids 808:829 specific triterpenoids 808:829 The TLC and HPLC profiles indicated that specific triterpenoids varied between white and regular strains. 28597443 4 52 theme different 640:648 arg1 stages 657:662 different growth stages 640:662 different growth stages 640:662 RESULTS The chemical profiles of A. cinnamomea extracts at different growth stages were compared using thin layer chromatography (TLC) and high performance liquid chromatography (HPLC). 28597443 7 53 dep CONCLUSIONS 1102:1112 arg1 change 1141:1146 change 1141:1146 could change color of the regular A. cinnamomea from orange-red to white by changing its secondary metabolism and growth condition 1135:1264 CONCLUSIONS Blue-light radiation could change color of the regular A. cinnamomea from orange-red to white by changing its secondary metabolism and growth condition. 28597443 7 54 theme regular 1161:1167 arg1 cinnamomea 1172:1181 the regular A. cinnamomea 1157:1181 the regular A. cinnamomea from orange-red to white 1157:1206 CONCLUSIONS Blue-light radiation could change color of the regular A. cinnamomea from orange-red to white by changing its secondary metabolism and growth condition. 28597443 3 55 theme A. 566:567 arg1 cinnamomea 569:578 naturally occurring and blue-light induced white A. cinnamomea 517:578 naturally occurring and blue-light induced white A. cinnamomea 517:578 Therefore it is of interest to study the chemical variation of regular orange-red strains and white strains, which included naturally occurring and blue-light induced white A. cinnamomea. 28597443 6 56 theme strain 925:930 arg1 similar 937:943 similar 937:943 similar 937:943 Moreover, the compounds of blue-light induced white strain were similar to those of naturally occurring white strain but retained specific chemical characteristics in more polar region of the HPLC chromatogram of regular strain. 28597443 6 56 theme strain 925:930 arg1 compounds 887:895 the compounds 883:895 the compounds of blue-light induced white strain 883:930 Moreover, the compounds of blue-light induced white strain were similar to those of naturally occurring white strain but retained specific chemical characteristics in more polar region of the HPLC chromatogram of regular strain. 28597443 9 57 theme fruiting 1578:1585 arg1 body 1587:1590 fruiting body 1578:1590 fruiting body 1578:1590 The ergostane-type triterpenoids were found existing in both young mycelia and old mycelia with fruiting body in artificial agar-plate medium culture, suggesting a more diversified biosynthetic pathway in artificial agar-plate culture rather than wild or submerged culture. 28597443 4 58 theme A. 614:615 arg1 extracts 628:635 A. cinnamomea extracts 614:635 A. cinnamomea extracts 614:635 RESULTS The chemical profiles of A. cinnamomea extracts at different growth stages were compared using thin layer chromatography (TLC) and high performance liquid chromatography (HPLC). 28597443 3 59 theme induced 552:558 arg1 cinnamomea 569:578 naturally occurring and blue-light induced white A. cinnamomea 517:578 naturally occurring and blue-light induced white A. cinnamomea 517:578 Therefore it is of interest to study the chemical variation of regular orange-red strains and white strains, which included naturally occurring and blue-light induced white A. cinnamomea. 28597443 1 60 theme unique 176:181 arg1 kanehirae 141:149 its host Cinnamomum kanehirae 121:149 its host Cinnamomum kanehirae 121:149 BACKGROUND Antrodia cinnamomea and its host Cinnamomum kanehirae are both endemic species unique to Taiwan. 28597443 1 60 theme unique 176:181 arg1 cinnamomea 106:115 BACKGROUND Antrodia cinnamomea 86:115 BACKGROUND Antrodia cinnamomea 86:115 BACKGROUND Antrodia cinnamomea and its host Cinnamomum kanehirae are both endemic species unique to Taiwan. 28597443 1 60 theme unique 176:181 arg1 species 168:174 both endemic species 155:174 both endemic species unique to Taiwan 155:191 BACKGROUND Antrodia cinnamomea and its host Cinnamomum kanehirae are both endemic species unique to Taiwan. 28597443 6 61 theme induced 911:917 arg1 strain 925:930 blue-light induced white strain 900:930 blue-light induced white strain 900:930 Moreover, the compounds of blue-light induced white strain were similar to those of naturally occurring white strain but retained specific chemical characteristics in more polar region of the HPLC chromatogram of regular strain. 28597443 9 62 located found 1520:1524 arg1 culture 1624:1630 artificial agar-plate medium culture 1595:1630 artificial agar-plate medium culture 1595:1630 The ergostane-type triterpenoids were found existing in both young mycelia and old mycelia with fruiting body in artificial agar-plate medium culture, suggesting a more diversified biosynthetic pathway in artificial agar-plate culture rather than wild or submerged culture. 28597443 9 62 located found 1520:1524 arg2 triterpenoids 1501:1513 The ergostane-type triterpenoids 1482:1513 The ergostane-type triterpenoids 1482:1513 The ergostane-type triterpenoids were found existing in both young mycelia and old mycelia with fruiting body in artificial agar-plate medium culture, suggesting a more diversified biosynthetic pathway in artificial agar-plate culture rather than wild or submerged culture. 28597443 8 63 theme white 1287:1291 arg1 strain 1293:1298 Naturally occurring white strain 1267:1298 Naturally occurring white strain 1267:1298 Naturally occurring white strain did not show a significantly different composition of triterpenoid profiles up to eight weeks old when compared with the triterpenoid profiles of the regular strain at the same age. 28597443 6 64 theme specific 1003:1010 arg1 characteristics 1021:1035 specific chemical characteristics 1003:1035 specific chemical characteristics 1003:1035 Moreover, the compounds of blue-light induced white strain were similar to those of naturally occurring white strain but retained specific chemical characteristics in more polar region of the HPLC chromatogram of regular strain. 28597443 8 65 from age 1477:1479 arg1 profiles 1434:1441 the triterpenoid profiles 1417:1441 the triterpenoid profiles of the regular strain at the same age 1417:1479 Naturally occurring white strain did not show a significantly different composition of triterpenoid profiles up to eight weeks old when compared with the triterpenoid profiles of the regular strain at the same age. 28597443 5 66 theme regular 856:862 arg1 strains 864:870 white and regular strains 846:870 white and regular strains 846:870 The TLC and HPLC profiles indicated that specific triterpenoids varied between white and regular strains. 28597443 4 67 from stages 657:662 arg1 profiles 602:609 The chemical profiles 589:609 The chemical profiles of A. cinnamomea extracts at different growth stages 589:662 RESULTS The chemical profiles of A. cinnamomea extracts at different growth stages were compared using thin layer chromatography (TLC) and high performance liquid chromatography (HPLC). 28597443 9 68 from pathway 1676:1682 arg1 culture 1747:1753 wild or submerged culture 1729:1753 wild or submerged culture 1729:1753 The ergostane-type triterpenoids were found existing in both young mycelia and old mycelia with fruiting body in artificial agar-plate medium culture, suggesting a more diversified biosynthetic pathway in artificial agar-plate culture rather than wild or submerged culture. 28597443 9 68 from pathway 1676:1682 arg1 culture 1709:1715 artificial agar-plate culture 1687:1715 artificial agar-plate culture 1687:1715 The ergostane-type triterpenoids were found existing in both young mycelia and old mycelia with fruiting body in artificial agar-plate medium culture, suggesting a more diversified biosynthetic pathway in artificial agar-plate culture rather than wild or submerged culture. 28597443 9 69 theme young 1543:1547 arg1 mycelia 1549:1555 young mycelia 1543:1555 young mycelia 1543:1555 The ergostane-type triterpenoids were found existing in both young mycelia and old mycelia with fruiting body in artificial agar-plate medium culture, suggesting a more diversified biosynthetic pathway in artificial agar-plate culture rather than wild or submerged culture. 28597443 4 70 theme performance 725:735 arg1 HPLC 760:763 HPLC 760:763 HPLC 760:763 RESULTS The chemical profiles of A. cinnamomea extracts at different growth stages were compared using thin layer chromatography (TLC) and high performance liquid chromatography (HPLC). 28597443 4 70 theme performance 725:735 arg1 chromatography 744:757 high performance liquid chromatography 720:757 high performance liquid chromatography (HPLC) 720:764 RESULTS The chemical profiles of A. cinnamomea extracts at different growth stages were compared using thin layer chromatography (TLC) and high performance liquid chromatography (HPLC). 28597443 1 71 theme Cinnamomum 130:139 arg1 kanehirae 141:149 its host Cinnamomum kanehirae 121:149 its host Cinnamomum kanehirae 121:149 BACKGROUND Antrodia cinnamomea and its host Cinnamomum kanehirae are both endemic species unique to Taiwan. 28597443 1 71 theme Cinnamomum 130:139 arg1 cinnamomea 106:115 BACKGROUND Antrodia cinnamomea 86:115 BACKGROUND Antrodia cinnamomea 86:115 BACKGROUND Antrodia cinnamomea and its host Cinnamomum kanehirae are both endemic species unique to Taiwan. 28597443 1 71 theme Cinnamomum 130:139 arg1 species 168:174 both endemic species 155:174 both endemic species unique to Taiwan 155:191 BACKGROUND Antrodia cinnamomea and its host Cinnamomum kanehirae are both endemic species unique to Taiwan. 28597443 2 72 from triterpenoids 272:284 arg1 rich 244:247 rich 244:247 rich 244:247 Many studies have confirmed that A. cinnamomea is rich in polysaccharides and triterpenoids that may carry medicinal effects in anti-cancer, anti-inflammation, anti-hypertension, and anti-oxidation. 28597443 8 73 theme triterpenoid 1354:1365 arg1 profiles 1367:1374 triterpenoid profiles 1354:1374 triterpenoid profiles up to eight weeks old 1354:1396 Naturally occurring white strain did not show a significantly different composition of triterpenoid profiles up to eight weeks old when compared with the triterpenoid profiles of the regular strain at the same age. 28597443 5 74 theme TLC 771:773 arg1 profiles 784:791 The TLC and HPLC profiles 767:791 The TLC and HPLC profiles 767:791 The TLC and HPLC profiles indicated that specific triterpenoids varied between white and regular strains. 28597443 5 75 theme HPLC 779:782 arg1 profiles 784:791 The TLC and HPLC profiles 767:791 The TLC and HPLC profiles 767:791 The TLC and HPLC profiles indicated that specific triterpenoids varied between white and regular strains. 28597443 1 76 theme endemic 160:166 arg1 kanehirae 141:149 its host Cinnamomum kanehirae 121:149 its host Cinnamomum kanehirae 121:149 BACKGROUND Antrodia cinnamomea and its host Cinnamomum kanehirae are both endemic species unique to Taiwan. 28597443 1 76 theme endemic 160:166 arg1 cinnamomea 106:115 BACKGROUND Antrodia cinnamomea 86:115 BACKGROUND Antrodia cinnamomea 86:115 BACKGROUND Antrodia cinnamomea and its host Cinnamomum kanehirae are both endemic species unique to Taiwan. 28597443 1 76 theme endemic 160:166 arg1 species 168:174 both endemic species 155:174 both endemic species unique to Taiwan 155:191 BACKGROUND Antrodia cinnamomea and its host Cinnamomum kanehirae are both endemic species unique to Taiwan. 28597443 0 77 from variation 11:19 arg1 cinnamomea 74:83 regular and white Antrodia cinnamomea 47:83 regular and white Antrodia cinnamomea 47:83 Phenologic variation of major triterpenoids in regular and white Antrodia cinnamomea. 28597443 7 78 from white 1202:1206 arg1 cinnamomea 1172:1181 the regular A. cinnamomea 1157:1181 the regular A. cinnamomea from orange-red to white 1157:1206 CONCLUSIONS Blue-light radiation could change color of the regular A. cinnamomea from orange-red to white by changing its secondary metabolism and growth condition. 28597443 7 78 from white 1202:1206 arg1 color 1148:1152 color 1148:1152 color of the regular A. cinnamomea from orange-red to white 1148:1206 CONCLUSIONS Blue-light radiation could change color of the regular A. cinnamomea from orange-red to white by changing its secondary metabolism and growth condition. 28597443 8 79 theme old 1394:1396 arg1 profiles 1367:1374 triterpenoid profiles 1354:1374 triterpenoid profiles up to eight weeks old 1354:1396 Naturally occurring white strain did not show a significantly different composition of triterpenoid profiles up to eight weeks old when compared with the triterpenoid profiles of the regular strain at the same age. 28597443 7 80 theme secondary 1224:1232 arg1 metabolism 1234:1243 its secondary metabolism 1220:1243 its secondary metabolism 1220:1243 CONCLUSIONS Blue-light radiation could change color of the regular A. cinnamomea from orange-red to white by changing its secondary metabolism and growth condition. 28597443 9 81 theme agar-plate 1606:1615 arg1 culture 1624:1630 artificial agar-plate medium culture 1595:1630 artificial agar-plate medium culture 1595:1630 The ergostane-type triterpenoids were found existing in both young mycelia and old mycelia with fruiting body in artificial agar-plate medium culture, suggesting a more diversified biosynthetic pathway in artificial agar-plate culture rather than wild or submerged culture. 28597443 3 82 theme regular 456:462 arg1 strains 475:481 regular orange-red strains 456:481 regular orange-red strains 456:481 Therefore it is of interest to study the chemical variation of regular orange-red strains and white strains, which included naturally occurring and blue-light induced white A. cinnamomea. 28597443 1 83 theme BACKGROUND 86:95 arg1 kanehirae 141:149 its host Cinnamomum kanehirae 121:149 its host Cinnamomum kanehirae 121:149 BACKGROUND Antrodia cinnamomea and its host Cinnamomum kanehirae are both endemic species unique to Taiwan. 28597443 1 83 theme BACKGROUND 86:95 arg1 cinnamomea 106:115 BACKGROUND Antrodia cinnamomea 86:115 BACKGROUND Antrodia cinnamomea 86:115 BACKGROUND Antrodia cinnamomea and its host Cinnamomum kanehirae are both endemic species unique to Taiwan. 28597443 1 83 theme BACKGROUND 86:95 arg1 species 168:174 both endemic species 155:174 both endemic species unique to Taiwan 155:191 BACKGROUND Antrodia cinnamomea and its host Cinnamomum kanehirae are both endemic species unique to Taiwan. 28597443 9 84 with mycelia 1549:1555 arg1 body 1587:1590 fruiting body 1578:1590 fruiting body 1578:1590 The ergostane-type triterpenoids were found existing in both young mycelia and old mycelia with fruiting body in artificial agar-plate medium culture, suggesting a more diversified biosynthetic pathway in artificial agar-plate culture rather than wild or submerged culture. 28597443 0 85 theme major 24:28 arg1 triterpenoids 30:42 major triterpenoids 24:42 major triterpenoids 24:42 Phenologic variation of major triterpenoids in regular and white Antrodia cinnamomea. 28597443 2 86 from rich 244:247 arg1 triterpenoids 272:284 triterpenoids 272:284 triterpenoids 272:284 Many studies have confirmed that A. cinnamomea is rich in polysaccharides and triterpenoids that may carry medicinal effects in anti-cancer, anti-inflammation, anti-hypertension, and anti-oxidation. 28597443 2 86 from rich 244:247 arg1 polysaccharides 252:266 polysaccharides 252:266 polysaccharides 252:266 Many studies have confirmed that A. cinnamomea is rich in polysaccharides and triterpenoids that may carry medicinal effects in anti-cancer, anti-inflammation, anti-hypertension, and anti-oxidation. 28597443 6 87 theme regular 1086:1092 arg1 strain 1094:1099 regular strain 1086:1099 regular strain 1086:1099 Moreover, the compounds of blue-light induced white strain were similar to those of naturally occurring white strain but retained specific chemical characteristics in more polar region of the HPLC chromatogram of regular strain. 28597443 4 88 theme chemical 593:600 arg1 profiles 602:609 The chemical profiles 589:609 The chemical profiles of A. cinnamomea extracts at different growth stages 589:662 RESULTS The chemical profiles of A. cinnamomea extracts at different growth stages were compared using thin layer chromatography (TLC) and high performance liquid chromatography (HPLC). 28597443 3 89 theme white 487:491 arg1 strains 493:499 white strains 487:499 white strains 487:499 Therefore it is of interest to study the chemical variation of regular orange-red strains and white strains, which included naturally occurring and blue-light induced white A. cinnamomea. 28597443 2 90 contain carry 295:299 arg3 anti-inflammation 335:351 anti-inflammation 335:351 anti-inflammation 335:351 Many studies have confirmed that A. cinnamomea is rich in polysaccharides and triterpenoids that may carry medicinal effects in anti-cancer, anti-inflammation, anti-hypertension, and anti-oxidation. 28597443 2 90 contain carry 295:299 arg2 effects 311:317 medicinal effects 301:317 medicinal effects 301:317 Many studies have confirmed that A. cinnamomea is rich in polysaccharides and triterpenoids that may carry medicinal effects in anti-cancer, anti-inflammation, anti-hypertension, and anti-oxidation. 28597443 2 90 contain carry 295:299 arg3 anti-oxidation 377:390 anti-oxidation 377:390 anti-oxidation 377:390 Many studies have confirmed that A. cinnamomea is rich in polysaccharides and triterpenoids that may carry medicinal effects in anti-cancer, anti-inflammation, anti-hypertension, and anti-oxidation. 28597443 2 90 contain carry 295:299 arg3 anti-cancer 322:332 anti-cancer 322:332 anti-cancer 322:332 Many studies have confirmed that A. cinnamomea is rich in polysaccharides and triterpenoids that may carry medicinal effects in anti-cancer, anti-inflammation, anti-hypertension, and anti-oxidation. 28597443 2 90 contain carry 295:299 arg1 triterpenoids 272:284 triterpenoids 272:284 triterpenoids 272:284 Many studies have confirmed that A. cinnamomea is rich in polysaccharides and triterpenoids that may carry medicinal effects in anti-cancer, anti-inflammation, anti-hypertension, and anti-oxidation. 28597443 2 90 contain carry 295:299 arg1 polysaccharides 252:266 polysaccharides 252:266 polysaccharides 252:266 Many studies have confirmed that A. cinnamomea is rich in polysaccharides and triterpenoids that may carry medicinal effects in anti-cancer, anti-inflammation, anti-hypertension, and anti-oxidation. 28597443 2 90 contain carry 295:299 arg3 anti-hypertension 354:370 anti-hypertension 354:370 anti-hypertension 354:370 Many studies have confirmed that A. cinnamomea is rich in polysaccharides and triterpenoids that may carry medicinal effects in anti-cancer, anti-inflammation, anti-hypertension, and anti-oxidation. 28597443 2 91 from polysaccharides 252:266 arg1 rich 244:247 rich 244:247 rich 244:247 Many studies have confirmed that A. cinnamomea is rich in polysaccharides and triterpenoids that may carry medicinal effects in anti-cancer, anti-inflammation, anti-hypertension, and anti-oxidation. 28597443 6 92 theme chromatogram 1070:1081 arg1 region 1051:1056 more polar region 1040:1056 more polar region of the HPLC chromatogram of regular strain 1040:1099 Moreover, the compounds of blue-light induced white strain were similar to those of naturally occurring white strain but retained specific chemical characteristics in more polar region of the HPLC chromatogram of regular strain. 28597443 3 93 theme strains 475:481 arg1 variation 443:451 the chemical variation 430:451 the chemical variation of regular orange-red strains and white strains 430:499 Therefore it is of interest to study the chemical variation of regular orange-red strains and white strains, which included naturally occurring and blue-light induced white A. cinnamomea. 28597443 7 94 theme cinnamomea 1172:1181 arg1 color 1148:1152 color 1148:1152 color of the regular A. cinnamomea from orange-red to white 1148:1206 CONCLUSIONS Blue-light radiation could change color of the regular A. cinnamomea from orange-red to white by changing its secondary metabolism and growth condition. 28597443 9 95 theme biosynthetic 1663:1674 arg1 pathway 1676:1682 a more diversified biosynthetic pathway 1644:1682 a more diversified biosynthetic pathway in artificial agar-plate culture rather than wild or submerged culture 1644:1753 The ergostane-type triterpenoids were found existing in both young mycelia and old mycelia with fruiting body in artificial agar-plate medium culture, suggesting a more diversified biosynthetic pathway in artificial agar-plate culture rather than wild or submerged culture. 28597443 8 96 theme strain 1458:1463 arg1 profiles 1434:1441 the triterpenoid profiles 1417:1441 the triterpenoid profiles of the regular strain at the same age 1417:1479 Naturally occurring white strain did not show a significantly different composition of triterpenoid profiles up to eight weeks old when compared with the triterpenoid profiles of the regular strain at the same age. 28597443 9 97 theme agar-plate 1698:1707 arg1 culture 1709:1715 artificial agar-plate culture 1687:1715 artificial agar-plate culture 1687:1715 The ergostane-type triterpenoids were found existing in both young mycelia and old mycelia with fruiting body in artificial agar-plate medium culture, suggesting a more diversified biosynthetic pathway in artificial agar-plate culture rather than wild or submerged culture. 28597443 4 98 theme growth 650:655 arg1 stages 657:662 different growth stages 640:662 different growth stages 640:662 RESULTS The chemical profiles of A. cinnamomea extracts at different growth stages were compared using thin layer chromatography (TLC) and high performance liquid chromatography (HPLC). 28258584 3 0 theme growth/shape 691:702 arg1 modulation 704:713 the nucleation and growth/shape modulation 672:713 modulation 704:713 The aim of this study was to describe the cell wall ultrastructure of Lithothamnion crispatum, a cosmopolitan rhodolith-forming coralline algal species collected near Salvador (Brazil), and examine the relationship between the organic matrix and the nucleation and growth/shape modulation of calcium carbonate crystals. 28258584 9 1 theme organizational 1501:1514 arg1 patterns 1516:1523 organizational patterns 1501:1523 organizational patterns 1501:1523 Biomineralization in L. crispatum is dependent on both the soluble and the insoluble organic matrix, which are involved in the control of mineral formation and organizational patterns through an organic matrix-mediated process. 28258584 5 2 from L. crispatum 858:869 arg1 crystals 844:851 the crystals 840:851 the crystals from L. crispatum 840:869 At the nanoscale, the crystals from L. crispatum consisted of several single crystallites assembled and associated with organic material. 28258584 3 3 theme cell 468:471 arg1 wall ultrastructure 473:491 the cell wall ultrastructure 464:491 the cell wall ultrastructure of Lithothamnion crispatum, a cosmopolitan rhodolith-forming coralline algal species collected near Salvador (Brazil), 464:610 The aim of this study was to describe the cell wall ultrastructure of Lithothamnion crispatum, a cosmopolitan rhodolith-forming coralline algal species collected near Salvador (Brazil), and examine the relationship between the organic matrix and the nucleation and growth/shape modulation of calcium carbonate crystals. 28258584 9 4 theme organic 1426:1432 arg1 matrix 1434:1439 organic matrix 1426:1439 organic matrix 1426:1439 Biomineralization in L. crispatum is dependent on both the soluble and the insoluble organic matrix, which are involved in the control of mineral formation and organizational patterns through an organic matrix-mediated process. 28258584 0 5 theme mineral 158:164 arg1 phase 166:170 the mineral phase 154:170 the mineral phase 154:170 Biomineralization of calcium carbonate in the cell wall of Lithothamnion crispatum (Hapalidiales, Rhodophyta): correlation between the organic matrix and the mineral phase. 28258584 2 6 from relationship 307:318 arg1 algae 382:386 coralline algae 372:386 coralline algae 372:386 However, the relationship between the mineral phase and the organic matrix in coralline algae has not yet been thoroughly examined. 28258584 2 7 theme mineral 332:338 arg1 phase 340:344 the mineral phase 328:344 the mineral phase 328:344 However, the relationship between the mineral phase and the organic matrix in coralline algae has not yet been thoroughly examined. 28258584 6 8 theme wall 1001:1004 arg1 bulk 984:987 the bulk 980:987 the bulk of the cell wall 980:1004 The crystallites in the bulk of the cell wall had a high level of spatial organization. 28258584 10 9 theme mineral 1599:1605 arg1 composition 1607:1617 mineral composition 1599:1617 mineral composition 1599:1617 This knowledge concerning the mineral composition and organizational patterns of crystals within the cell walls should be taken into account in future studies of changing ocean conditions as they represent important factors influencing the physico-chemical interactions between rhodoliths and the environment in coralline reefs. 28258584 0 10 from Biomineralization 0:16 arg1 wall 51:54 the cell wall 42:54 the cell wall of Lithothamnion crispatum (Hapalidiales, Rhodophyta) 42:108 Biomineralization of calcium carbonate in the cell wall of Lithothamnion crispatum (Hapalidiales, Rhodophyta): correlation between the organic matrix and the mineral phase. 28258584 10 11 theme ocean 1740:1744 arg1 conditions 1746:1755 changing ocean conditions 1731:1755 changing ocean conditions 1731:1755 This knowledge concerning the mineral composition and organizational patterns of crystals within the cell walls should be taken into account in future studies of changing ocean conditions as they represent important factors influencing the physico-chemical interactions between rhodoliths and the environment in coralline reefs. 28258584 9 12 theme matrix-mediated 1544:1558 arg1 process 1560:1566 an organic matrix-mediated process 1533:1566 an organic matrix-mediated process 1533:1566 Biomineralization in L. crispatum is dependent on both the soluble and the insoluble organic matrix, which are involved in the control of mineral formation and organizational patterns through an organic matrix-mediated process. 28258584 6 13 contain had 1006:1008 arg1 crystallites 964:975 The crystallites 960:975 The crystallites in the bulk of the cell wall 960:1004 The crystallites in the bulk of the cell wall had a high level of spatial organization. 28258584 6 13 contain had 1006:1008 arg2 level 1017:1021 a high level 1010:1021 a high level of spatial organization 1010:1045 The crystallites in the bulk of the cell wall had a high level of spatial organization. 28258584 6 14 theme cell 996:999 arg1 wall 1001:1004 the cell wall 992:1004 the cell wall 992:1004 The crystallites in the bulk of the cell wall had a high level of spatial organization. 28258584 5 15 dep crystallites 899:910 arg1 associated 926:935 associated 926:935 associated with organic material 926:957 At the nanoscale, the crystals from L. crispatum consisted of several single crystallites assembled and associated with organic material. 28258584 5 15 dep crystallites 899:910 arg1 assembled 912:920 assembled 912:920 assembled 912:920 At the nanoscale, the crystals from L. crispatum consisted of several single crystallites assembled and associated with organic material. 28258584 3 16 theme calcium 718:724 arg1 crystals 736:743 calcium carbonate crystals 718:743 calcium carbonate crystals 718:743 The aim of this study was to describe the cell wall ultrastructure of Lithothamnion crispatum, a cosmopolitan rhodolith-forming coralline algal species collected near Salvador (Brazil), and examine the relationship between the organic matrix and the nucleation and growth/shape modulation of calcium carbonate crystals. 28258584 7 17 with sectioning 1125:1134 arg1 microtome 1143:1151 a microtome 1141:1151 a microtome 1141:1151 However, the crystals displayed cleavages in the (104) faces after ultrathin sectioning with a microtome. 28258584 10 18 theme crystals 1650:1657 arg1 composition 1607:1617 mineral composition 1599:1617 mineral composition 1599:1617 This knowledge concerning the mineral composition and organizational patterns of crystals within the cell walls should be taken into account in future studies of changing ocean conditions as they represent important factors influencing the physico-chemical interactions between rhodoliths and the environment in coralline reefs. 28258584 10 18 theme crystals 1650:1657 arg1 patterns 1638:1645 organizational patterns 1623:1645 organizational patterns 1623:1645 This knowledge concerning the mineral composition and organizational patterns of crystals within the cell walls should be taken into account in future studies of changing ocean conditions as they represent important factors influencing the physico-chemical interactions between rhodoliths and the environment in coralline reefs. 28258584 3 19 theme cosmopolitan 523:534 arg1 crispatum 510:518 Lithothamnion crispatum 496:518 Lithothamnion crispatum 496:518 The aim of this study was to describe the cell wall ultrastructure of Lithothamnion crispatum, a cosmopolitan rhodolith-forming coralline algal species collected near Salvador (Brazil), and examine the relationship between the organic matrix and the nucleation and growth/shape modulation of calcium carbonate crystals. 28258584 3 19 theme cosmopolitan 523:534 arg1 species 570:576 a cosmopolitan rhodolith-forming coralline algal species 521:576 a cosmopolitan rhodolith-forming coralline algal species collected near Salvador (Brazil) 521:609 The aim of this study was to describe the cell wall ultrastructure of Lithothamnion crispatum, a cosmopolitan rhodolith-forming coralline algal species collected near Salvador (Brazil), and examine the relationship between the organic matrix and the nucleation and growth/shape modulation of calcium carbonate crystals. 28258584 5 20 theme organic 942:948 arg1 material 950:957 organic material 942:957 organic material 942:957 At the nanoscale, the crystals from L. crispatum consisted of several single crystallites assembled and associated with organic material. 28258584 3 21 theme carbonate 726:734 arg1 crystals 736:743 calcium carbonate crystals 718:743 calcium carbonate crystals 718:743 The aim of this study was to describe the cell wall ultrastructure of Lithothamnion crispatum, a cosmopolitan rhodolith-forming coralline algal species collected near Salvador (Brazil), and examine the relationship between the organic matrix and the nucleation and growth/shape modulation of calcium carbonate crystals. 28258584 3 22 theme crispatum 510:518 arg1 wall ultrastructure 473:491 the cell wall ultrastructure 464:491 the cell wall ultrastructure of Lithothamnion crispatum, a cosmopolitan rhodolith-forming coralline algal species collected near Salvador (Brazil), 464:610 The aim of this study was to describe the cell wall ultrastructure of Lithothamnion crispatum, a cosmopolitan rhodolith-forming coralline algal species collected near Salvador (Brazil), and examine the relationship between the organic matrix and the nucleation and growth/shape modulation of calcium carbonate crystals. 28258584 8 23 theme important 1174:1182 arg1 model 1184:1188 an important model 1171:1188 an important model for biomineralization studies 1171:1218 This organism is an important model for biomineralization studies as the crystallographic data do not fit in any of the general biomineralization processes described for other organisms. 28258584 8 23 theme important 1174:1182 arg1 organism 1159:1166 This organism 1154:1166 This organism 1154:1166 This organism is an important model for biomineralization studies as the crystallographic data do not fit in any of the general biomineralization processes described for other organisms. 28258584 2 24 theme coralline 372:380 arg1 algae 382:386 coralline algae 372:386 coralline algae 372:386 However, the relationship between the mineral phase and the organic matrix in coralline algae has not yet been thoroughly examined. 28258584 0 25 theme cell 46:49 arg1 wall 51:54 the cell wall 42:54 the cell wall of Lithothamnion crispatum (Hapalidiales, Rhodophyta) 42:108 Biomineralization of calcium carbonate in the cell wall of Lithothamnion crispatum (Hapalidiales, Rhodophyta): correlation between the organic matrix and the mineral phase. 28258584 10 26 dep composition 1607:1617 arg1 the 1595:1597 the 1595:1597 the 1595:1597 This knowledge concerning the mineral composition and organizational patterns of crystals within the cell walls should be taken into account in future studies of changing ocean conditions as they represent important factors influencing the physico-chemical interactions between rhodoliths and the environment in coralline reefs. 28258584 10 27 theme future 1713:1718 arg1 studies 1720:1726 future studies 1713:1726 future studies of changing ocean conditions 1713:1755 This knowledge concerning the mineral composition and organizational patterns of crystals within the cell walls should be taken into account in future studies of changing ocean conditions as they represent important factors influencing the physico-chemical interactions between rhodoliths and the environment in coralline reefs. 28258584 10 28 from environment 1866:1876 arg1 reefs 1891:1895 coralline reefs 1881:1895 coralline reefs 1881:1895 This knowledge concerning the mineral composition and organizational patterns of crystals within the cell walls should be taken into account in future studies of changing ocean conditions as they represent important factors influencing the physico-chemical interactions between rhodoliths and the environment in coralline reefs. 28258584 10 29 from rhodoliths 1847:1856 arg1 reefs 1891:1895 coralline reefs 1881:1895 coralline reefs 1881:1895 This knowledge concerning the mineral composition and organizational patterns of crystals within the cell walls should be taken into account in future studies of changing ocean conditions as they represent important factors influencing the physico-chemical interactions between rhodoliths and the environment in coralline reefs. 28258584 3 30 theme algal 564:568 arg1 crispatum 510:518 Lithothamnion crispatum 496:518 Lithothamnion crispatum 496:518 The aim of this study was to describe the cell wall ultrastructure of Lithothamnion crispatum, a cosmopolitan rhodolith-forming coralline algal species collected near Salvador (Brazil), and examine the relationship between the organic matrix and the nucleation and growth/shape modulation of calcium carbonate crystals. 28258584 3 30 theme algal 564:568 arg1 species 570:576 a cosmopolitan rhodolith-forming coralline algal species 521:576 a cosmopolitan rhodolith-forming coralline algal species collected near Salvador (Brazil) 521:609 The aim of this study was to describe the cell wall ultrastructure of Lithothamnion crispatum, a cosmopolitan rhodolith-forming coralline algal species collected near Salvador (Brazil), and examine the relationship between the organic matrix and the nucleation and growth/shape modulation of calcium carbonate crystals. 28258584 10 31 theme organizational 1623:1636 arg1 patterns 1638:1645 organizational patterns 1623:1645 organizational patterns 1623:1645 This knowledge concerning the mineral composition and organizational patterns of crystals within the cell walls should be taken into account in future studies of changing ocean conditions as they represent important factors influencing the physico-chemical interactions between rhodoliths and the environment in coralline reefs. 28258584 7 32 from cleavages 1080:1088 arg1 faces 1103:1107 the (104) faces 1093:1107 the (104) faces 1093:1107 However, the crystals displayed cleavages in the (104) faces after ultrathin sectioning with a microtome. 28258584 2 33 theme organic 354:360 arg1 matrix 362:367 the organic matrix 350:367 the organic matrix 350:367 However, the relationship between the mineral phase and the organic matrix in coralline algae has not yet been thoroughly examined. 28258584 0 34 theme carbonate 29:37 arg1 Biomineralization 0:16 Biomineralization 0:16 Biomineralization of calcium carbonate in the cell wall of Lithothamnion crispatum (Hapalidiales, Rhodophyta): correlation between the organic matrix and the mineral phase. 0:171 Biomineralization of calcium carbonate in the cell wall of Lithothamnion crispatum (Hapalidiales, Rhodophyta): correlation between the organic matrix and the mineral phase. 28258584 8 35 theme biomineralization 1282:1298 arg1 processes 1300:1308 the general biomineralization processes 1270:1308 the general biomineralization processes described for other organisms 1270:1338 This organism is an important model for biomineralization studies as the crystallographic data do not fit in any of the general biomineralization processes described for other organisms. 28258584 8 36 theme general 1274:1280 arg1 processes 1300:1308 the general biomineralization processes 1270:1308 the general biomineralization processes described for other organisms 1270:1338 This organism is an important model for biomineralization studies as the crystallographic data do not fit in any of the general biomineralization processes described for other organisms. 28258584 0 37 dep Lithothamnion 59:71 arg1 crispatum 73:81 Lithothamnion crispatum 59:81 Lithothamnion crispatum (Hapalidiales, Rhodophyta) 59:108 Biomineralization of calcium carbonate in the cell wall of Lithothamnion crispatum (Hapalidiales, Rhodophyta): correlation between the organic matrix and the mineral phase. 28258584 10 38 theme coralline 1881:1889 arg1 reefs 1891:1895 coralline reefs 1881:1895 coralline reefs 1881:1895 This knowledge concerning the mineral composition and organizational patterns of crystals within the cell walls should be taken into account in future studies of changing ocean conditions as they represent important factors influencing the physico-chemical interactions between rhodoliths and the environment in coralline reefs. 28258584 0 39 theme calcium 21:27 arg1 carbonate 29:37 calcium carbonate 21:37 calcium carbonate 21:37 Biomineralization of calcium carbonate in the cell wall of Lithothamnion crispatum (Hapalidiales, Rhodophyta): correlation between the organic matrix and the mineral phase. 28258584 1 40 theme coralline 262:270 arg1 mineralization 278:291 coralline algae mineralization 262:291 coralline algae mineralization 262:291 Over the past few decades, progress has been made toward understanding the mechanisms of coralline algae mineralization. 28258584 10 41 theme important 1775:1783 arg1 factors 1785:1791 important factors 1775:1791 important factors influencing the physico-chemical interactions between rhodoliths and the environment in coralline reefs 1775:1895 This knowledge concerning the mineral composition and organizational patterns of crystals within the cell walls should be taken into account in future studies of changing ocean conditions as they represent important factors influencing the physico-chemical interactions between rhodoliths and the environment in coralline reefs. 28258584 9 42 dep soluble 1400:1406 arg1 matrix 1434:1439 organic matrix 1426:1439 organic matrix 1426:1439 Biomineralization in L. crispatum is dependent on both the soluble and the insoluble organic matrix, which are involved in the control of mineral formation and organizational patterns through an organic matrix-mediated process. 28258584 3 43 theme coralline 554:562 arg1 crispatum 510:518 Lithothamnion crispatum 496:518 Lithothamnion crispatum 496:518 The aim of this study was to describe the cell wall ultrastructure of Lithothamnion crispatum, a cosmopolitan rhodolith-forming coralline algal species collected near Salvador (Brazil), and examine the relationship between the organic matrix and the nucleation and growth/shape modulation of calcium carbonate crystals. 28258584 3 43 theme coralline 554:562 arg1 species 570:576 a cosmopolitan rhodolith-forming coralline algal species 521:576 a cosmopolitan rhodolith-forming coralline algal species collected near Salvador (Brazil) 521:609 The aim of this study was to describe the cell wall ultrastructure of Lithothamnion crispatum, a cosmopolitan rhodolith-forming coralline algal species collected near Salvador (Brazil), and examine the relationship between the organic matrix and the nucleation and growth/shape modulation of calcium carbonate crystals. 28258584 9 44 theme organic 1536:1542 arg1 process 1560:1566 an organic matrix-mediated process 1533:1566 an organic matrix-mediated process 1533:1566 Biomineralization in L. crispatum is dependent on both the soluble and the insoluble organic matrix, which are involved in the control of mineral formation and organizational patterns through an organic matrix-mediated process. 28258584 1 45 theme past 182:185 arg1 decades 191:197 the past few decades 178:197 the past few decades 178:197 Over the past few decades, progress has been made toward understanding the mechanisms of coralline algae mineralization. 28258584 8 46 theme biomineralization 1194:1210 arg1 studies 1212:1218 biomineralization studies 1194:1218 biomineralization studies 1194:1218 This organism is an important model for biomineralization studies as the crystallographic data do not fit in any of the general biomineralization processes described for other organisms. 28258584 1 47 theme algae 272:276 arg1 mineralization 278:291 coralline algae mineralization 262:291 coralline algae mineralization 262:291 Over the past few decades, progress has been made toward understanding the mechanisms of coralline algae mineralization. 28258584 6 48 theme organization 1034:1045 arg1 level 1017:1021 a high level 1010:1021 a high level of spatial organization 1010:1045 The crystallites in the bulk of the cell wall had a high level of spatial organization. 28258584 10 49 theme cell 1670:1673 arg1 walls 1675:1679 the cell walls 1666:1679 the cell walls 1666:1679 This knowledge concerning the mineral composition and organizational patterns of crystals within the cell walls should be taken into account in future studies of changing ocean conditions as they represent important factors influencing the physico-chemical interactions between rhodoliths and the environment in coralline reefs. 28258584 1 50 theme few 187:189 arg1 decades 191:197 the past few decades 178:197 the past few decades 178:197 Over the past few decades, progress has been made toward understanding the mechanisms of coralline algae mineralization. 28258584 8 51 theme crystallographic 1227:1242 arg1 data 1244:1247 the crystallographic data 1223:1247 the crystallographic data 1223:1247 This organism is an important model for biomineralization studies as the crystallographic data do not fit in any of the general biomineralization processes described for other organisms. 28258584 1 52 theme mineralization 278:291 arg1 mechanisms 248:257 the mechanisms 244:257 the mechanisms of coralline algae mineralization 244:291 Over the past few decades, progress has been made toward understanding the mechanisms of coralline algae mineralization. 28258584 4 53 theme nanostructured 748:761 arg1 pattern 763:769 A nanostructured pattern 746:769 A nanostructured pattern 746:769 A nanostructured pattern was observed in L. crispatum along the cell walls. 28258584 4 54 located observed 775:782 arg1 L. crispatum 787:798 L. crispatum 787:798 L. crispatum 787:798 A nanostructured pattern was observed in L. crispatum along the cell walls. 28258584 4 54 located observed 775:782 arg2 pattern 763:769 A nanostructured pattern 746:769 A nanostructured pattern 746:769 A nanostructured pattern was observed in L. crispatum along the cell walls. 28258584 6 55 theme spatial 1026:1032 arg1 organization 1034:1045 spatial organization 1026:1045 spatial organization 1026:1045 The crystallites in the bulk of the cell wall had a high level of spatial organization. 28258584 10 56 theme changing 1731:1738 arg1 conditions 1746:1755 changing ocean conditions 1731:1755 changing ocean conditions 1731:1755 This knowledge concerning the mineral composition and organizational patterns of crystals within the cell walls should be taken into account in future studies of changing ocean conditions as they represent important factors influencing the physico-chemical interactions between rhodoliths and the environment in coralline reefs. 28258584 9 57 theme mineral 1479:1485 arg1 formation 1487:1495 mineral formation 1479:1495 mineral formation 1479:1495 Biomineralization in L. crispatum is dependent on both the soluble and the insoluble organic matrix, which are involved in the control of mineral formation and organizational patterns through an organic matrix-mediated process. 28258584 3 58 theme nucleation 676:685 arg1 modulation 704:713 the nucleation and growth/shape modulation 672:713 modulation 704:713 The aim of this study was to describe the cell wall ultrastructure of Lithothamnion crispatum, a cosmopolitan rhodolith-forming coralline algal species collected near Salvador (Brazil), and examine the relationship between the organic matrix and the nucleation and growth/shape modulation of calcium carbonate crystals. 28258584 0 59 theme organic 135:141 arg1 matrix 143:148 the organic matrix 131:148 the organic matrix 131:148 Biomineralization of calcium carbonate in the cell wall of Lithothamnion crispatum (Hapalidiales, Rhodophyta): correlation between the organic matrix and the mineral phase. 28258584 9 60 theme formation 1487:1495 arg1 control 1468:1474 the control 1464:1474 the control of mineral formation and organizational patterns through an organic matrix-mediated process 1464:1566 Biomineralization in L. crispatum is dependent on both the soluble and the insoluble organic matrix, which are involved in the control of mineral formation and organizational patterns through an organic matrix-mediated process. 28258584 10 61 theme physico-chemical 1809:1824 arg1 interactions 1826:1837 the physico-chemical interactions 1805:1837 the physico-chemical interactions between rhodoliths and the environment in coralline reefs 1805:1895 This knowledge concerning the mineral composition and organizational patterns of crystals within the cell walls should be taken into account in future studies of changing ocean conditions as they represent important factors influencing the physico-chemical interactions between rhodoliths and the environment in coralline reefs. 28258584 6 62 from crystallites 964:975 arg1 bulk 984:987 the bulk 980:987 the bulk of the cell wall 980:1004 The crystallites in the bulk of the cell wall had a high level of spatial organization. 28258584 3 63 theme crystals 736:743 arg1 matrix 661:666 the organic matrix 649:666 the organic matrix 649:666 The aim of this study was to describe the cell wall ultrastructure of Lithothamnion crispatum, a cosmopolitan rhodolith-forming coralline algal species collected near Salvador (Brazil), and examine the relationship between the organic matrix and the nucleation and growth/shape modulation of calcium carbonate crystals. 28258584 3 63 theme crystals 736:743 arg1 modulation 704:713 the nucleation and growth/shape modulation 672:713 modulation 704:713 The aim of this study was to describe the cell wall ultrastructure of Lithothamnion crispatum, a cosmopolitan rhodolith-forming coralline algal species collected near Salvador (Brazil), and examine the relationship between the organic matrix and the nucleation and growth/shape modulation of calcium carbonate crystals. 28258584 3 64 theme rhodolith-forming 536:552 arg1 crispatum 510:518 Lithothamnion crispatum 496:518 Lithothamnion crispatum 496:518 The aim of this study was to describe the cell wall ultrastructure of Lithothamnion crispatum, a cosmopolitan rhodolith-forming coralline algal species collected near Salvador (Brazil), and examine the relationship between the organic matrix and the nucleation and growth/shape modulation of calcium carbonate crystals. 28258584 3 64 theme rhodolith-forming 536:552 arg1 species 570:576 a cosmopolitan rhodolith-forming coralline algal species 521:576 a cosmopolitan rhodolith-forming coralline algal species collected near Salvador (Brazil) 521:609 The aim of this study was to describe the cell wall ultrastructure of Lithothamnion crispatum, a cosmopolitan rhodolith-forming coralline algal species collected near Salvador (Brazil), and examine the relationship between the organic matrix and the nucleation and growth/shape modulation of calcium carbonate crystals. 28258584 10 65 theme conditions 1746:1755 arg1 studies 1720:1726 future studies 1713:1726 future studies of changing ocean conditions 1713:1755 This knowledge concerning the mineral composition and organizational patterns of crystals within the cell walls should be taken into account in future studies of changing ocean conditions as they represent important factors influencing the physico-chemical interactions between rhodoliths and the environment in coralline reefs. 28258584 5 66 theme single 892:897 arg1 crystallites 899:910 several single crystallites 884:910 several single crystallites assembled and associated with organic material 884:957 At the nanoscale, the crystals from L. crispatum consisted of several single crystallites assembled and associated with organic material. 28258584 8 67 theme other 1324:1328 arg1 organisms 1330:1338 other organisms 1324:1338 other organisms 1324:1338 This organism is an important model for biomineralization studies as the crystallographic data do not fit in any of the general biomineralization processes described for other organisms. 28258584 3 68 theme study 442:446 arg1 aim 430:432 The aim 426:432 The aim of this study 426:446 The aim of this study was to describe the cell wall ultrastructure of Lithothamnion crispatum, a cosmopolitan rhodolith-forming coralline algal species collected near Salvador (Brazil), and examine the relationship between the organic matrix and the nucleation and growth/shape modulation of calcium carbonate crystals. 28258584 0 69 theme Lithothamnion 59:71 arg1 wall 51:54 the cell wall 42:54 the cell wall of Lithothamnion crispatum (Hapalidiales, Rhodophyta) 42:108 Biomineralization of calcium carbonate in the cell wall of Lithothamnion crispatum (Hapalidiales, Rhodophyta): correlation between the organic matrix and the mineral phase. 28258584 3 70 theme organic 653:659 arg1 matrix 661:666 the organic matrix 649:666 the organic matrix 649:666 The aim of this study was to describe the cell wall ultrastructure of Lithothamnion crispatum, a cosmopolitan rhodolith-forming coralline algal species collected near Salvador (Brazil), and examine the relationship between the organic matrix and the nucleation and growth/shape modulation of calcium carbonate crystals. 28258584 4 71 theme cell 810:813 arg1 walls 815:819 the cell walls 806:819 the cell walls 806:819 A nanostructured pattern was observed in L. crispatum along the cell walls. 28258584 9 72 theme patterns 1516:1523 arg1 control 1468:1474 the control 1464:1474 the control of mineral formation and organizational patterns through an organic matrix-mediated process 1464:1566 Biomineralization in L. crispatum is dependent on both the soluble and the insoluble organic matrix, which are involved in the control of mineral formation and organizational patterns through an organic matrix-mediated process. 28258584 5 73 theme several 884:890 arg1 crystallites 899:910 several single crystallites 884:910 several single crystallites assembled and associated with organic material 884:957 At the nanoscale, the crystals from L. crispatum consisted of several single crystallites assembled and associated with organic material. 28258584 6 74 theme high 1012:1015 arg1 level 1017:1021 a high level 1010:1021 a high level of spatial organization 1010:1045 The crystallites in the bulk of the cell wall had a high level of spatial organization. 28258584 7 75 theme ultrathin 1115:1123 arg1 sectioning 1125:1134 ultrathin sectioning 1115:1134 ultrathin sectioning with a microtome 1115:1151 However, the crystals displayed cleavages in the (104) faces after ultrathin sectioning with a microtome. 28258584 0 76 dep Biomineralization 0:16 arg1 correlation 111:121 correlation 111:121 Biomineralization of calcium carbonate in the cell wall of Lithothamnion crispatum (Hapalidiales, Rhodophyta): correlation between the organic matrix and the mineral phase. 0:171 Biomineralization of calcium carbonate in the cell wall of Lithothamnion crispatum (Hapalidiales, Rhodophyta): correlation between the organic matrix and the mineral phase. 28258584 3 77 theme Lithothamnion 496:508 arg1 crispatum 510:518 Lithothamnion crispatum 496:518 Lithothamnion crispatum 496:518 The aim of this study was to describe the cell wall ultrastructure of Lithothamnion crispatum, a cosmopolitan rhodolith-forming coralline algal species collected near Salvador (Brazil), and examine the relationship between the organic matrix and the nucleation and growth/shape modulation of calcium carbonate crystals. 28258584 3 77 theme Lithothamnion 496:508 arg1 species 570:576 a cosmopolitan rhodolith-forming coralline algal species 521:576 a cosmopolitan rhodolith-forming coralline algal species collected near Salvador (Brazil) 521:609 The aim of this study was to describe the cell wall ultrastructure of Lithothamnion crispatum, a cosmopolitan rhodolith-forming coralline algal species collected near Salvador (Brazil), and examine the relationship between the organic matrix and the nucleation and growth/shape modulation of calcium carbonate crystals. 27260215 0 0 theme sensitive 90:98 arg1 techniques 106:115 sensitive LC/MS techniques 90:115 sensitive LC/MS techniques 90:115 Advanced assessment of the physicochemical characteristics of Remicade® and Inflectra® by sensitive LC/MS techniques. 27260215 2 1 theme brand 566:570 arg1 Remicade® 578:586 Remicade® 578:586 Remicade® 578:586 Specifically, we focus on infliximab and compared the glycan profiles, higher order structures, and their host cell proteins (HCPs) of the reference and biosimilar products, which have the brand names Remicade® and Inflectra®, respectively. 27260215 2 1 theme brand 566:570 arg1 names 572:576 the brand names 562:576 the brand names Remicade® and Inflectra® 562:601 Specifically, we focus on infliximab and compared the glycan profiles, higher order structures, and their host cell proteins (HCPs) of the reference and biosimilar products, which have the brand names Remicade® and Inflectra®, respectively. 27260215 2 1 theme brand 566:570 arg1 Inflectra® 592:601 Inflectra® 592:601 Inflectra® 592:601 Specifically, we focus on infliximab and compared the glycan profiles, higher order structures, and their host cell proteins (HCPs) of the reference and biosimilar products, which have the brand names Remicade® and Inflectra®, respectively. 27260215 7 2 theme higher-order 1223:1234 arg1 similarity 1236:1245 the higher-order similarity 1219:1245 the higher-order similarity of the 2 molecules 1219:1264 Hydrogen deuterium exchange (HDX) analyses further confirmed the higher-order similarity of the 2 molecules. 27260215 8 3 link N-linked 1404:1411 arg1 glycans 1413:1419 the N-linked glycans 1400:1419 the N-linked glycans 1400:1419 These results demonstrated only very slight differences between the 2 products, which, interestingly, seemed to be in the area where the N-linked glycans reside. 27260215 9 4 attach present 1510:1516 arg2 HCPs 1500:1503 the same 2 HCPs 1489:1503 the same 2 HCPs 1489:1503 The HCP analysis by a 2D-UPLC IMS-MS approach revealed that the same 2 HCPs were present in both mAb samples. 27260215 9 4 attach present 1510:1516 arg1 samples 1530:1536 both mAb samples 1521:1536 both mAb samples 1521:1536 The HCP analysis by a 2D-UPLC IMS-MS approach revealed that the same 2 HCPs were present in both mAb samples. 27260215 9 4 attach present 1510:1516 arg2 present 1510:1516 present 1510:1516 present 1510:1516 The HCP analysis by a 2D-UPLC IMS-MS approach revealed that the same 2 HCPs were present in both mAb samples. 27260215 6 5 link α-linked 1063:1070 arg1 pairs 1082:1086 α-linked galactose pairs 1063:1086 α-linked galactose pairs 1063:1086 Glycans terminated with N-glycolylneuraminic acid were generally observed to be at higher normalized abundance levels on the biosimilar mAb, while those possessing α-linked galactose pairs were more often expressed at higher levels on the reference molecule. 27260215 6 6 theme galactose 1072:1080 arg1 pairs 1082:1086 α-linked galactose pairs 1063:1086 α-linked galactose pairs 1063:1086 Glycans terminated with N-glycolylneuraminic acid were generally observed to be at higher normalized abundance levels on the biosimilar mAb, while those possessing α-linked galactose pairs were more often expressed at higher levels on the reference molecule. 27260215 9 7 theme 2D-UPLC 1451:1457 arg1 approach 1466:1473 a 2D-UPLC IMS-MS approach 1449:1473 a 2D-UPLC IMS-MS approach 1449:1473 The HCP analysis by a 2D-UPLC IMS-MS approach revealed that the same 2 HCPs were present in both mAb samples. 27260215 4 8 theme glycan 720:725 arg1 analysis 737:744 The glycan profiling analysis 716:744 The glycan profiling analysis 716:744 The glycan profiling analysis demonstrated a high degree of similarity, especially among the higher abundance glycans. 27260215 0 9 theme LC/MS 100:104 arg1 techniques 106:115 sensitive LC/MS techniques 90:115 sensitive LC/MS techniques 90:115 Advanced assessment of the physicochemical characteristics of Remicade® and Inflectra® by sensitive LC/MS techniques. 27260215 9 10 theme same 1493:1496 arg1 present 1510:1516 present 1510:1516 present 1510:1516 The HCP analysis by a 2D-UPLC IMS-MS approach revealed that the same 2 HCPs were present in both mAb samples. 27260215 9 10 theme same 1493:1496 arg1 HCPs 1500:1503 the same 2 HCPs 1489:1503 the same 2 HCPs 1489:1503 The HCP analysis by a 2D-UPLC IMS-MS approach revealed that the same 2 HCPs were present in both mAb samples. 27260215 6 11 theme normalized 989:998 arg1 levels 1010:1015 normalized abundance levels 989:1015 higher normalized abundance levels 982:1015 Glycans terminated with N-glycolylneuraminic acid were generally observed to be at higher normalized abundance levels on the biosimilar mAb, while those possessing α-linked galactose pairs were more often expressed at higher levels on the reference molecule. 27260215 7 12 theme exchange 1177:1184 arg1 analyses 1192:1199 Hydrogen deuterium exchange (HDX) analyses 1158:1199 Hydrogen deuterium exchange (HDX) analyses 1158:1199 Hydrogen deuterium exchange (HDX) analyses further confirmed the higher-order similarity of the 2 molecules. 27260215 6 13 theme higher 1117:1122 arg1 levels 1124:1129 higher levels 1117:1129 higher levels 1117:1129 Glycans terminated with N-glycolylneuraminic acid were generally observed to be at higher normalized abundance levels on the biosimilar mAb, while those possessing α-linked galactose pairs were more often expressed at higher levels on the reference molecule. 27260215 6 14 theme α-linked 1063:1070 arg1 pairs 1082:1086 α-linked galactose pairs 1063:1086 α-linked galactose pairs 1063:1086 Glycans terminated with N-glycolylneuraminic acid were generally observed to be at higher normalized abundance levels on the biosimilar mAb, while those possessing α-linked galactose pairs were more often expressed at higher levels on the reference molecule. 27260215 1 15 theme ultra-performance 163:179 arg1 chromatography 188:201 ultra-performance liquid chromatography 163:201 ultra-performance liquid chromatography coupled to mass spectrometry (MS) and ion-mobility spectrometry (IMS) 163:271 In this study, we demonstrate the utility of ultra-performance liquid chromatography coupled to mass spectrometry (MS) and ion-mobility spectrometry (IMS) to characterize and compare reference and biosimilar monoclonal antibodies (mAbs) at an advanced level. 27260215 2 16 theme cell 488:491 arg1 proteins 493:500 their host cell proteins 477:500 their host cell proteins (HCPs) 477:507 Specifically, we focus on infliximab and compared the glycan profiles, higher order structures, and their host cell proteins (HCPs) of the reference and biosimilar products, which have the brand names Remicade® and Inflectra®, respectively. 27260215 2 16 theme cell 488:491 arg1 HCPs 503:506 HCPs 503:506 HCPs 503:506 Specifically, we focus on infliximab and compared the glycan profiles, higher order structures, and their host cell proteins (HCPs) of the reference and biosimilar products, which have the brand names Remicade® and Inflectra®, respectively. 27260215 1 17 theme advanced 361:368 arg1 level 370:374 an advanced level 358:374 an advanced level 358:374 In this study, we demonstrate the utility of ultra-performance liquid chromatography coupled to mass spectrometry (MS) and ion-mobility spectrometry (IMS) to characterize and compare reference and biosimilar monoclonal antibodies (mAbs) at an advanced level. 27260215 10 18 theme analyses 1577:1584 arg1 types 1568:1572 these types 1562:1572 these types of analyses 1562:1584 Our ability to perform these types of analyses and acquire insightful data for biosimilarity assessment is based upon our highly sensitive UPLC MS and IMS methods. 27260215 0 19 theme Advanced 0:7 arg1 assessment 9:18 Advanced assessment 0:18 Advanced assessment of the physicochemical characteristics of Remicade® and Inflectra® by sensitive LC/MS techniques. 0:116 Advanced assessment of the physicochemical characteristics of Remicade® and Inflectra® by sensitive LC/MS techniques. 27260215 1 20 theme liquid 181:186 arg1 chromatography 188:201 ultra-performance liquid chromatography 163:201 ultra-performance liquid chromatography coupled to mass spectrometry (MS) and ion-mobility spectrometry (IMS) 163:271 In this study, we demonstrate the utility of ultra-performance liquid chromatography coupled to mass spectrometry (MS) and ion-mobility spectrometry (IMS) to characterize and compare reference and biosimilar monoclonal antibodies (mAbs) at an advanced level. 27260215 7 21 theme Hydrogen 1158:1165 arg1 HDX 1187:1189 HDX 1187:1189 HDX 1187:1189 Hydrogen deuterium exchange (HDX) analyses further confirmed the higher-order similarity of the 2 molecules. 27260215 7 21 theme Hydrogen 1158:1165 arg1 exchange 1177:1184 Hydrogen deuterium exchange 1158:1184 Hydrogen deuterium exchange (HDX) analyses 1158:1199 Hydrogen deuterium exchange (HDX) analyses further confirmed the higher-order similarity of the 2 molecules. 27260215 9 22 located present 1510:1516 arg2 HCPs 1500:1503 the same 2 HCPs 1489:1503 the same 2 HCPs 1489:1503 The HCP analysis by a 2D-UPLC IMS-MS approach revealed that the same 2 HCPs were present in both mAb samples. 27260215 9 22 located present 1510:1516 arg1 samples 1530:1536 both mAb samples 1521:1536 both mAb samples 1521:1536 The HCP analysis by a 2D-UPLC IMS-MS approach revealed that the same 2 HCPs were present in both mAb samples. 27260215 9 22 located present 1510:1516 arg2 present 1510:1516 present 1510:1516 present 1510:1516 The HCP analysis by a 2D-UPLC IMS-MS approach revealed that the same 2 HCPs were present in both mAb samples. 27260215 4 23 theme abundance 816:824 arg1 glycans 826:832 the higher abundance glycans 805:832 the higher abundance glycans 805:832 The glycan profiling analysis demonstrated a high degree of similarity, especially among the higher abundance glycans. 27260215 0 24 theme Inflectra® 76:85 arg1 characteristics 43:57 the physicochemical characteristics 23:57 the physicochemical characteristics of Remicade® and Inflectra® 23:85 Advanced assessment of the physicochemical characteristics of Remicade® and Inflectra® by sensitive LC/MS techniques. 27260215 6 25 theme reference 1138:1146 arg1 molecule 1148:1155 the reference molecule 1134:1155 the reference molecule 1134:1155 Glycans terminated with N-glycolylneuraminic acid were generally observed to be at higher normalized abundance levels on the biosimilar mAb, while those possessing α-linked galactose pairs were more often expressed at higher levels on the reference molecule. 27260215 1 26 theme chromatography 188:201 arg1 utility 152:158 the utility 148:158 the utility of ultra-performance liquid chromatography coupled to mass spectrometry (MS) and ion-mobility spectrometry (IMS) to characterize and compare reference and biosimilar monoclonal antibodies (mAbs) at an advanced level 148:374 In this study, we demonstrate the utility of ultra-performance liquid chromatography coupled to mass spectrometry (MS) and ion-mobility spectrometry (IMS) to characterize and compare reference and biosimilar monoclonal antibodies (mAbs) at an advanced level. 27260215 2 27 theme glycan 431:436 arg1 profiles 438:445 the glycan profiles 427:445 the glycan profiles 427:445 Specifically, we focus on infliximab and compared the glycan profiles, higher order structures, and their host cell proteins (HCPs) of the reference and biosimilar products, which have the brand names Remicade® and Inflectra®, respectively. 27260215 4 28 theme higher 809:814 arg1 glycans 826:832 the higher abundance glycans 805:832 the higher abundance glycans 805:832 The glycan profiling analysis demonstrated a high degree of similarity, especially among the higher abundance glycans. 27260215 9 29 theme mAb 1526:1528 arg1 samples 1530:1536 both mAb samples 1521:1536 both mAb samples 1521:1536 The HCP analysis by a 2D-UPLC IMS-MS approach revealed that the same 2 HCPs were present in both mAb samples. 27260215 2 30 theme reference 516:524 arg1 products 541:548 the reference and biosimilar products 512:548 products 541:548 Specifically, we focus on infliximab and compared the glycan profiles, higher order structures, and their host cell proteins (HCPs) of the reference and biosimilar products, which have the brand names Remicade® and Inflectra®, respectively. 27260215 10 31 theme biosimilarity 1618:1630 arg1 assessment 1632:1641 biosimilarity assessment 1618:1641 biosimilarity assessment 1618:1641 Our ability to perform these types of analyses and acquire insightful data for biosimilarity assessment is based upon our highly sensitive UPLC MS and IMS methods. 27260215 2 32 dep names 572:576 arg1 Remicade® 578:586 Remicade® 578:586 Remicade® 578:586 Specifically, we focus on infliximab and compared the glycan profiles, higher order structures, and their host cell proteins (HCPs) of the reference and biosimilar products, which have the brand names Remicade® and Inflectra®, respectively. 27260215 2 32 dep names 572:576 arg1 names 572:576 the brand names 562:576 the brand names Remicade® and Inflectra® 562:601 Specifically, we focus on infliximab and compared the glycan profiles, higher order structures, and their host cell proteins (HCPs) of the reference and biosimilar products, which have the brand names Remicade® and Inflectra®, respectively. 27260215 2 32 dep names 572:576 arg1 Inflectra® 592:601 Inflectra® 592:601 Inflectra® 592:601 Specifically, we focus on infliximab and compared the glycan profiles, higher order structures, and their host cell proteins (HCPs) of the reference and biosimilar products, which have the brand names Remicade® and Inflectra®, respectively. 27260215 6 33 dep higher 982:987 arg1 levels 1010:1015 normalized abundance levels 989:1015 higher normalized abundance levels 982:1015 Glycans terminated with N-glycolylneuraminic acid were generally observed to be at higher normalized abundance levels on the biosimilar mAb, while those possessing α-linked galactose pairs were more often expressed at higher levels on the reference molecule. 27260215 10 34 theme sensitive 1668:1676 arg1 MS 1683:1684 our highly sensitive UPLC MS 1657:1684 our highly sensitive UPLC MS 1657:1684 Our ability to perform these types of analyses and acquire insightful data for biosimilarity assessment is based upon our highly sensitive UPLC MS and IMS methods. 27260215 1 35 theme mass 214:217 arg1 MS 233:234 MS 233:234 MS 233:234 In this study, we demonstrate the utility of ultra-performance liquid chromatography coupled to mass spectrometry (MS) and ion-mobility spectrometry (IMS) to characterize and compare reference and biosimilar monoclonal antibodies (mAbs) at an advanced level. 27260215 1 35 theme mass 214:217 arg1 spectrometry 219:230 mass spectrometry 214:230 mass spectrometry (MS) 214:235 In this study, we demonstrate the utility of ultra-performance liquid chromatography coupled to mass spectrometry (MS) and ion-mobility spectrometry (IMS) to characterize and compare reference and biosimilar monoclonal antibodies (mAbs) at an advanced level. 27260215 0 36 theme characteristics 43:57 arg1 assessment 9:18 Advanced assessment 0:18 Advanced assessment of the physicochemical characteristics of Remicade® and Inflectra® by sensitive LC/MS techniques. 0:116 Advanced assessment of the physicochemical characteristics of Remicade® and Inflectra® by sensitive LC/MS techniques. 27260215 3 37 theme high 703:706 arg1 degree 708:713 a very high degree 696:713 a very high degree 696:713 Overall, the biosimilar attributes mirrored those of the reference product to a very high degree. 27260215 7 38 theme deuterium 1167:1175 arg1 HDX 1187:1189 HDX 1187:1189 HDX 1187:1189 Hydrogen deuterium exchange (HDX) analyses further confirmed the higher-order similarity of the 2 molecules. 27260215 7 38 theme deuterium 1167:1175 arg1 exchange 1177:1184 Hydrogen deuterium exchange 1158:1184 Hydrogen deuterium exchange (HDX) analyses 1158:1199 Hydrogen deuterium exchange (HDX) analyses further confirmed the higher-order similarity of the 2 molecules. 27260215 4 39 theme similarity 776:785 arg1 degree 766:771 a high degree 759:771 a high degree of similarity 759:785 The glycan profiling analysis demonstrated a high degree of similarity, especially among the higher abundance glycans. 27260215 10 40 dep MS 1683:1684 arg1 methods 1694:1700 methods 1694:1700 methods 1694:1700 Our ability to perform these types of analyses and acquire insightful data for biosimilarity assessment is based upon our highly sensitive UPLC MS and IMS methods. 27260215 6 41 theme biosimilar 1024:1033 arg1 mAb 1035:1037 the biosimilar mAb 1020:1037 the biosimilar mAb 1020:1037 Glycans terminated with N-glycolylneuraminic acid were generally observed to be at higher normalized abundance levels on the biosimilar mAb, while those possessing α-linked galactose pairs were more often expressed at higher levels on the reference molecule. 27260215 0 42 theme physicochemical 27:41 arg1 characteristics 43:57 the physicochemical characteristics 23:57 the physicochemical characteristics of Remicade® and Inflectra® 23:85 Advanced assessment of the physicochemical characteristics of Remicade® and Inflectra® by sensitive LC/MS techniques. 27260215 6 43 theme N-glycolylneuraminic 923:942 arg1 acid 944:947 N-glycolylneuraminic acid 923:947 N-glycolylneuraminic acid 923:947 Glycans terminated with N-glycolylneuraminic acid were generally observed to be at higher normalized abundance levels on the biosimilar mAb, while those possessing α-linked galactose pairs were more often expressed at higher levels on the reference molecule. 27260215 2 44 theme order 455:459 arg1 structures 461:470 higher order structures 448:470 higher order structures 448:470 Specifically, we focus on infliximab and compared the glycan profiles, higher order structures, and their host cell proteins (HCPs) of the reference and biosimilar products, which have the brand names Remicade® and Inflectra®, respectively. 27260215 0 45 theme Remicade® 62:70 arg1 characteristics 43:57 the physicochemical characteristics 23:57 the physicochemical characteristics of Remicade® and Inflectra® 23:85 Advanced assessment of the physicochemical characteristics of Remicade® and Inflectra® by sensitive LC/MS techniques. 27260215 3 46 theme reference 675:683 arg1 product 685:691 the reference product 671:691 the reference product 671:691 Overall, the biosimilar attributes mirrored those of the reference product to a very high degree. 27260215 5 47 theme lower 874:878 arg1 glycans 890:896 the lower abundance glycans 870:896 the lower abundance glycans 870:896 Some differences were observed for the lower abundance glycans. 27260215 1 48 theme biosimilar 315:324 arg1 mAbs 349:352 mAbs 349:352 mAbs 349:352 In this study, we demonstrate the utility of ultra-performance liquid chromatography coupled to mass spectrometry (MS) and ion-mobility spectrometry (IMS) to characterize and compare reference and biosimilar monoclonal antibodies (mAbs) at an advanced level. 27260215 1 48 theme biosimilar 315:324 arg1 antibodies 337:346 biosimilar monoclonal antibodies 315:346 biosimilar monoclonal antibodies (mAbs) 315:353 In this study, we demonstrate the utility of ultra-performance liquid chromatography coupled to mass spectrometry (MS) and ion-mobility spectrometry (IMS) to characterize and compare reference and biosimilar monoclonal antibodies (mAbs) at an advanced level. 27260215 2 49 theme products 541:548 arg1 proteins 493:500 their host cell proteins 477:500 their host cell proteins (HCPs) 477:507 Specifically, we focus on infliximab and compared the glycan profiles, higher order structures, and their host cell proteins (HCPs) of the reference and biosimilar products, which have the brand names Remicade® and Inflectra®, respectively. 27260215 2 49 theme products 541:548 arg1 profiles 438:445 the glycan profiles 427:445 the glycan profiles 427:445 Specifically, we focus on infliximab and compared the glycan profiles, higher order structures, and their host cell proteins (HCPs) of the reference and biosimilar products, which have the brand names Remicade® and Inflectra®, respectively. 27260215 2 49 theme products 541:548 arg1 HCPs 503:506 HCPs 503:506 HCPs 503:506 Specifically, we focus on infliximab and compared the glycan profiles, higher order structures, and their host cell proteins (HCPs) of the reference and biosimilar products, which have the brand names Remicade® and Inflectra®, respectively. 27260215 2 49 theme products 541:548 arg1 structures 461:470 higher order structures 448:470 higher order structures 448:470 Specifically, we focus on infliximab and compared the glycan profiles, higher order structures, and their host cell proteins (HCPs) of the reference and biosimilar products, which have the brand names Remicade® and Inflectra®, respectively. 27260215 3 50 theme biosimilar 631:640 arg1 attributes 642:651 the biosimilar attributes 627:651 the biosimilar attributes 627:651 Overall, the biosimilar attributes mirrored those of the reference product to a very high degree. 27260215 5 51 theme abundance 880:888 arg1 glycans 890:896 the lower abundance glycans 870:896 the lower abundance glycans 870:896 Some differences were observed for the lower abundance glycans. 27260215 9 52 from samples 1530:1536 arg1 present 1510:1516 present 1510:1516 present 1510:1516 The HCP analysis by a 2D-UPLC IMS-MS approach revealed that the same 2 HCPs were present in both mAb samples. 27260215 9 52 from samples 1530:1536 arg1 HCPs 1500:1503 the same 2 HCPs 1489:1503 the same 2 HCPs 1489:1503 The HCP analysis by a 2D-UPLC IMS-MS approach revealed that the same 2 HCPs were present in both mAb samples. 27260215 1 53 theme monoclonal 326:335 arg1 mAbs 349:352 mAbs 349:352 mAbs 349:352 In this study, we demonstrate the utility of ultra-performance liquid chromatography coupled to mass spectrometry (MS) and ion-mobility spectrometry (IMS) to characterize and compare reference and biosimilar monoclonal antibodies (mAbs) at an advanced level. 27260215 1 53 theme monoclonal 326:335 arg1 antibodies 337:346 biosimilar monoclonal antibodies 315:346 biosimilar monoclonal antibodies (mAbs) 315:353 In this study, we demonstrate the utility of ultra-performance liquid chromatography coupled to mass spectrometry (MS) and ion-mobility spectrometry (IMS) to characterize and compare reference and biosimilar monoclonal antibodies (mAbs) at an advanced level. 27260215 2 54 theme biosimilar 530:539 arg1 products 541:548 the reference and biosimilar products 512:548 products 541:548 Specifically, we focus on infliximab and compared the glycan profiles, higher order structures, and their host cell proteins (HCPs) of the reference and biosimilar products, which have the brand names Remicade® and Inflectra®, respectively. 27260215 2 55 contain have 557:560 arg2 Inflectra® 592:601 Inflectra® 592:601 Inflectra® 592:601 Specifically, we focus on infliximab and compared the glycan profiles, higher order structures, and their host cell proteins (HCPs) of the reference and biosimilar products, which have the brand names Remicade® and Inflectra®, respectively. 27260215 2 55 contain have 557:560 arg2 Remicade® 578:586 Remicade® 578:586 Remicade® 578:586 Specifically, we focus on infliximab and compared the glycan profiles, higher order structures, and their host cell proteins (HCPs) of the reference and biosimilar products, which have the brand names Remicade® and Inflectra®, respectively. 27260215 2 55 contain have 557:560 arg1 products 541:548 the reference and biosimilar products 512:548 products 541:548 Specifically, we focus on infliximab and compared the glycan profiles, higher order structures, and their host cell proteins (HCPs) of the reference and biosimilar products, which have the brand names Remicade® and Inflectra®, respectively. 27260215 2 55 contain have 557:560 arg2 names 572:576 the brand names 562:576 the brand names Remicade® and Inflectra® 562:601 Specifically, we focus on infliximab and compared the glycan profiles, higher order structures, and their host cell proteins (HCPs) of the reference and biosimilar products, which have the brand names Remicade® and Inflectra®, respectively. 27260215 10 56 theme UPLC 1678:1681 arg1 MS 1683:1684 our highly sensitive UPLC MS 1657:1684 our highly sensitive UPLC MS 1657:1684 Our ability to perform these types of analyses and acquire insightful data for biosimilarity assessment is based upon our highly sensitive UPLC MS and IMS methods. 27260215 4 57 theme profiling 727:735 arg1 analysis 737:744 The glycan profiling analysis 716:744 The glycan profiling analysis 716:744 The glycan profiling analysis demonstrated a high degree of similarity, especially among the higher abundance glycans. 27260215 9 58 from present 1510:1516 arg1 samples 1530:1536 both mAb samples 1521:1536 both mAb samples 1521:1536 The HCP analysis by a 2D-UPLC IMS-MS approach revealed that the same 2 HCPs were present in both mAb samples. 27260215 7 59 theme molecules 1256:1264 arg1 similarity 1236:1245 the higher-order similarity 1219:1245 the higher-order similarity of the 2 molecules 1219:1264 Hydrogen deuterium exchange (HDX) analyses further confirmed the higher-order similarity of the 2 molecules. 27260215 2 60 theme host 483:486 arg1 proteins 493:500 their host cell proteins 477:500 their host cell proteins (HCPs) 477:507 Specifically, we focus on infliximab and compared the glycan profiles, higher order structures, and their host cell proteins (HCPs) of the reference and biosimilar products, which have the brand names Remicade® and Inflectra®, respectively. 27260215 2 60 theme host 483:486 arg1 HCPs 503:506 HCPs 503:506 HCPs 503:506 Specifically, we focus on infliximab and compared the glycan profiles, higher order structures, and their host cell proteins (HCPs) of the reference and biosimilar products, which have the brand names Remicade® and Inflectra®, respectively. 27260215 8 61 theme N-linked 1404:1411 arg1 glycans 1413:1419 the N-linked glycans 1400:1419 the N-linked glycans 1400:1419 These results demonstrated only very slight differences between the 2 products, which, interestingly, seemed to be in the area where the N-linked glycans reside. 27260215 9 62 theme HCP 1433:1435 arg1 analysis 1437:1444 The HCP analysis 1429:1444 The HCP analysis by a 2D-UPLC IMS-MS approach 1429:1473 The HCP analysis by a 2D-UPLC IMS-MS approach revealed that the same 2 HCPs were present in both mAb samples. 27260215 9 63 theme IMS-MS 1459:1464 arg1 approach 1466:1473 a 2D-UPLC IMS-MS approach 1449:1473 a 2D-UPLC IMS-MS approach 1449:1473 The HCP analysis by a 2D-UPLC IMS-MS approach revealed that the same 2 HCPs were present in both mAb samples. 27260215 10 64 theme insightful 1598:1607 arg1 data 1609:1612 insightful data 1598:1612 insightful data for biosimilarity assessment 1598:1641 Our ability to perform these types of analyses and acquire insightful data for biosimilarity assessment is based upon our highly sensitive UPLC MS and IMS methods. 27260215 6 65 theme abundance 1000:1008 arg1 levels 1010:1015 normalized abundance levels 989:1015 higher normalized abundance levels 982:1015 Glycans terminated with N-glycolylneuraminic acid were generally observed to be at higher normalized abundance levels on the biosimilar mAb, while those possessing α-linked galactose pairs were more often expressed at higher levels on the reference molecule. 27260215 2 66 theme higher 448:453 arg1 structures 461:470 higher order structures 448:470 higher order structures 448:470 Specifically, we focus on infliximab and compared the glycan profiles, higher order structures, and their host cell proteins (HCPs) of the reference and biosimilar products, which have the brand names Remicade® and Inflectra®, respectively. 27260215 4 67 theme high 761:764 arg1 degree 766:771 a high degree 759:771 a high degree of similarity 759:785 The glycan profiling analysis demonstrated a high degree of similarity, especially among the higher abundance glycans. 27260215 8 68 theme slight 1304:1309 arg1 differences 1311:1321 only very slight differences 1294:1321 only very slight differences 1294:1321 These results demonstrated only very slight differences between the 2 products, which, interestingly, seemed to be in the area where the N-linked glycans reside. 27260215 6 69 contain possessing 1052:1061 arg1 those 1046:1050 those 1046:1050 those 1046:1050 Glycans terminated with N-glycolylneuraminic acid were generally observed to be at higher normalized abundance levels on the biosimilar mAb, while those possessing α-linked galactose pairs were more often expressed at higher levels on the reference molecule. 27260215 6 69 contain possessing 1052:1061 arg2 pairs 1082:1086 α-linked galactose pairs 1063:1086 α-linked galactose pairs 1063:1086 Glycans terminated with N-glycolylneuraminic acid were generally observed to be at higher normalized abundance levels on the biosimilar mAb, while those possessing α-linked galactose pairs were more often expressed at higher levels on the reference molecule. 27260215 1 70 theme ion-mobility 241:252 arg1 IMS 268:270 IMS 268:270 IMS 268:270 In this study, we demonstrate the utility of ultra-performance liquid chromatography coupled to mass spectrometry (MS) and ion-mobility spectrometry (IMS) to characterize and compare reference and biosimilar monoclonal antibodies (mAbs) at an advanced level. 27260215 1 70 theme ion-mobility 241:252 arg1 spectrometry 254:265 ion-mobility spectrometry 241:265 ion-mobility spectrometry (IMS) 241:271 In this study, we demonstrate the utility of ultra-performance liquid chromatography coupled to mass spectrometry (MS) and ion-mobility spectrometry (IMS) to characterize and compare reference and biosimilar monoclonal antibodies (mAbs) at an advanced level. 24985322 8 0 theme neurotensin 1082:1092 arg1 N-terminus 1068:1077 the N-terminus 1064:1077 the N-terminus of neurotensin 1064:1092 We conclude that the N-terminus of neurotensin probably functions as an affinity enhancer for binding to sortilin by engaging the second binding site. 24985322 8 0 theme neurotensin 1082:1092 arg1 enhancer 1128:1135 an affinity enhancer 1116:1135 an affinity enhancer for binding to sortilin 1116:1159 We conclude that the N-terminus of neurotensin probably functions as an affinity enhancer for binding to sortilin by engaging the second binding site. 24985322 4 1 theme new 463:465 arg1 structure 473:481 a new 2.7 Å structure 461:481 a new 2.7 Å structure 461:481 To this end, we have determined a new 2.7 Å structure using a crystal grown with a 10-fold increased concentration of neurotensin. 24985322 12 2 gly glycosylations 1607:1620 arg1 sortilin 1645:1652 CHO-expressed human sortilin 1625:1652 CHO-expressed human sortilin 1625:1652 We have, furthermore, mapped all N-linked glycosylations of CHO-expressed human sortilin by mass spectrometry and find that their locations are compatible with membrane insertion of the hydrophobic loops. 24985322 9 3 dep degree 1296:1301 arg1 the 1292:1294 the 1292:1294 the 1292:1294 Crystal packing differs partly from the previous structure, which may be due to variations in the degree and pattern of glycosylations. 24985322 5 4 dep represent 664:672 arg1 either 657:662 either 657:662 either 657:662 Here a second peptide fragment was observed within the Vps10 β-propeller, which may in principle either represent a second molecule of neurotensin or the N-terminal part of the molecule bound at the previously identified binding site. 24985322 5 5 theme Vps10 615:619 arg1 β-propeller 621:631 the Vps10 β-propeller 611:631 the Vps10 β-propeller 611:631 Here a second peptide fragment was observed within the Vps10 β-propeller, which may in principle either represent a second molecule of neurotensin or the N-terminal part of the molecule bound at the previously identified binding site. 24985322 6 6 theme in 804:805 arg1 experiments 821:831 in vitro binding experiments 804:831 in vitro binding experiments 804:831 However, in vitro binding experiments strongly favor the latter hypothesis. 24985322 12 7 theme N-linked 1598:1605 arg1 glycosylations 1607:1620 all N-linked glycosylations 1594:1620 all N-linked glycosylations of CHO-expressed human sortilin 1594:1652 We have, furthermore, mapped all N-linked glycosylations of CHO-expressed human sortilin by mass spectrometry and find that their locations are compatible with membrane insertion of the hydrophobic loops. 24985322 4 8 theme Å 471:471 arg1 structure 473:481 a new 2.7 Å structure 461:481 a new 2.7 Å structure 461:481 To this end, we have determined a new 2.7 Å structure using a crystal grown with a 10-fold increased concentration of neurotensin. 24985322 3 9 with properties 368:377 arg1 neurotensin 416:426 neurotensin 416:426 neurotensin 416:426 Here we set out to further characterize the structural properties of sortilin and its interaction with neurotensin. 24985322 7 10 from affinity 999:1006 arg1 context 1011:1017 context 1011:1017 context of full-length neurotensin 1011:1044 Neurotensin thus appears to bind with a 1:1 stoichiometry, and whereas the N-terminus does not bind on its own, it enhances the affinity in context of full-length neurotensin. 24985322 6 11 theme latter 852:857 arg1 hypothesis 859:868 the latter hypothesis 848:868 the latter hypothesis 848:868 However, in vitro binding experiments strongly favor the latter hypothesis. 24985322 10 12 theme hydrophobic 1358:1368 arg1 loop 1370:1373 a notable hydrophobic loop 1348:1373 a notable hydrophobic loop 1348:1373 Consequently, a notable hydrophobic loop, not modeled previously, could now be traced. 24985322 5 13 theme second 567:572 arg1 fragment 582:589 a second peptide fragment 565:589 a second peptide fragment 565:589 Here a second peptide fragment was observed within the Vps10 β-propeller, which may in principle either represent a second molecule of neurotensin or the N-terminal part of the molecule bound at the previously identified binding site. 24985322 2 14 from structure 211:219 arg1 complex 248:254 complex 248:254 complex with one of its ligands, the tridecapeptide neurotensin 248:310 We have previously reported a 2.0-Å structure of the Vps10 ectodomain in complex with one of its ligands, the tridecapeptide neurotensin. 24985322 4 15 theme neurotensin 547:557 arg1 concentration 530:542 a 10-fold increased concentration 510:542 a 10-fold increased concentration of neurotensin 510:557 To this end, we have determined a new 2.7 Å structure using a crystal grown with a 10-fold increased concentration of neurotensin. 24985322 5 16 theme neurotensin 695:705 arg1 molecule 683:690 a second molecule 674:690 a second molecule of neurotensin 674:705 Here a second peptide fragment was observed within the Vps10 β-propeller, which may in principle either represent a second molecule of neurotensin or the N-terminal part of the molecule bound at the previously identified binding site. 24985322 5 16 theme neurotensin 695:705 arg1 part 725:728 the N-terminal part 710:728 the N-terminal part of the molecule bound at the previously identified binding site 710:792 Here a second peptide fragment was observed within the Vps10 β-propeller, which may in principle either represent a second molecule of neurotensin or the N-terminal part of the molecule bound at the previously identified binding site. 24985322 7 17 theme full-length 1022:1032 arg1 neurotensin 1034:1044 full-length neurotensin 1022:1044 full-length neurotensin 1022:1044 Neurotensin thus appears to bind with a 1:1 stoichiometry, and whereas the N-terminus does not bind on its own, it enhances the affinity in context of full-length neurotensin. 24985322 5 18 theme peptide 574:580 arg1 fragment 582:589 a second peptide fragment 565:589 a second peptide fragment 565:589 Here a second peptide fragment was observed within the Vps10 β-propeller, which may in principle either represent a second molecule of neurotensin or the N-terminal part of the molecule bound at the previously identified binding site. 24985322 8 19 theme second 1177:1182 arg1 site 1192:1195 the second binding site 1173:1195 the second binding site 1173:1195 We conclude that the N-terminus of neurotensin probably functions as an affinity enhancer for binding to sortilin by engaging the second binding site. 24985322 0 20 theme domain 38:43 arg1 structure 15:23 the structure 11:23 the structure of the Vps10 domain of human sortilin 11:61 Revisiting the structure of the Vps10 domain of human sortilin and its interaction with neurotensin. 24985322 0 20 theme domain 38:43 arg1 interaction 71:81 its interaction 67:81 its interaction with neurotensin 67:98 Revisiting the structure of the Vps10 domain of human sortilin and its interaction with neurotensin. 24985322 7 21 theme neurotensin 1034:1044 arg1 context 1011:1017 context 1011:1017 context of full-length neurotensin 1011:1044 Neurotensin thus appears to bind with a 1:1 stoichiometry, and whereas the N-terminus does not bind on its own, it enhances the affinity in context of full-length neurotensin. 24985322 10 22 theme notable 1350:1356 arg1 loop 1370:1373 a notable hydrophobic loop 1348:1373 a notable hydrophobic loop 1348:1373 Consequently, a notable hydrophobic loop, not modeled previously, could now be traced. 24985322 3 23 theme structural 357:366 arg1 properties 368:377 the structural properties 353:377 the structural properties of sortilin 353:389 Here we set out to further characterize the structural properties of sortilin and its interaction with neurotensin. 24985322 12 24 theme membrane 1725:1732 arg1 insertion 1734:1742 membrane insertion 1725:1742 membrane insertion of the hydrophobic loops 1725:1767 We have, furthermore, mapped all N-linked glycosylations of CHO-expressed human sortilin by mass spectrometry and find that their locations are compatible with membrane insertion of the hydrophobic loops. 24985322 12 25 theme sortilin 1645:1652 arg1 glycosylations 1607:1620 all N-linked glycosylations 1594:1620 all N-linked glycosylations of CHO-expressed human sortilin 1594:1652 We have, furthermore, mapped all N-linked glycosylations of CHO-expressed human sortilin by mass spectrometry and find that their locations are compatible with membrane insertion of the hydrophobic loops. 24985322 2 26 theme tridecapeptide 285:298 arg1 neurotensin 300:310 the tridecapeptide neurotensin 281:310 the tridecapeptide neurotensin 281:310 We have previously reported a 2.0-Å structure of the Vps10 ectodomain in complex with one of its ligands, the tridecapeptide neurotensin. 24985322 2 26 theme tridecapeptide 285:298 arg1 one 261:263 one 261:263 one 261:263 We have previously reported a 2.0-Å structure of the Vps10 ectodomain in complex with one of its ligands, the tridecapeptide neurotensin. 24985322 2 26 theme tridecapeptide 285:298 arg1 ligands 272:278 its ligands 268:278 its ligands 268:278 We have previously reported a 2.0-Å structure of the Vps10 ectodomain in complex with one of its ligands, the tridecapeptide neurotensin. 24985322 8 27 theme affinity 1119:1126 arg1 enhancer 1128:1135 an affinity enhancer 1116:1135 an affinity enhancer for binding to sortilin 1116:1159 We conclude that the N-terminus of neurotensin probably functions as an affinity enhancer for binding to sortilin by engaging the second binding site. 24985322 8 27 theme affinity 1119:1126 arg1 N-terminus 1068:1077 the N-terminus 1064:1077 the N-terminus of neurotensin 1064:1092 We conclude that the N-terminus of neurotensin probably functions as an affinity enhancer for binding to sortilin by engaging the second binding site. 24985322 11 28 theme neighboring 1471:1481 arg1 loop 1483:1486 a neighboring loop 1469:1486 a neighboring loop 1469:1486 A computational analysis suggests that this and a neighboring loop may insert into the membrane and thus restrain movement of the Vps10 domain. 24985322 8 29 theme binding 1184:1190 arg1 site 1192:1195 the second binding site 1173:1195 the second binding site 1173:1195 We conclude that the N-terminus of neurotensin probably functions as an affinity enhancer for binding to sortilin by engaging the second binding site. 24985322 5 30 theme identified 770:779 arg1 site 789:792 the previously identified binding site 755:792 the previously identified binding site 755:792 Here a second peptide fragment was observed within the Vps10 β-propeller, which may in principle either represent a second molecule of neurotensin or the N-terminal part of the molecule bound at the previously identified binding site. 24985322 0 31 with interaction 71:81 arg1 neurotensin 88:98 neurotensin 88:98 neurotensin 88:98 Revisiting the structure of the Vps10 domain of human sortilin and its interaction with neurotensin. 24985322 5 32 theme binding 781:787 arg1 site 789:792 the previously identified binding site 755:792 the previously identified binding site 755:792 Here a second peptide fragment was observed within the Vps10 β-propeller, which may in principle either represent a second molecule of neurotensin or the N-terminal part of the molecule bound at the previously identified binding site. 24985322 4 33 theme increased 520:528 arg1 concentration 530:542 a 10-fold increased concentration 510:542 a 10-fold increased concentration of neurotensin 510:557 To this end, we have determined a new 2.7 Å structure using a crystal grown with a 10-fold increased concentration of neurotensin. 24985322 9 34 from variations 1278:1287 arg1 pattern 1307:1313 pattern 1307:1313 pattern 1307:1313 Crystal packing differs partly from the previous structure, which may be due to variations in the degree and pattern of glycosylations. 24985322 9 34 from variations 1278:1287 arg1 degree 1296:1301 degree 1296:1301 degree 1296:1301 Crystal packing differs partly from the previous structure, which may be due to variations in the degree and pattern of glycosylations. 24985322 2 35 theme ligands 272:278 arg1 neurotensin 300:310 the tridecapeptide neurotensin 281:310 the tridecapeptide neurotensin 281:310 We have previously reported a 2.0-Å structure of the Vps10 ectodomain in complex with one of its ligands, the tridecapeptide neurotensin. 24985322 2 35 theme ligands 272:278 arg1 one 261:263 one 261:263 one 261:263 We have previously reported a 2.0-Å structure of the Vps10 ectodomain in complex with one of its ligands, the tridecapeptide neurotensin. 24985322 2 35 theme ligands 272:278 arg1 ligands 272:278 its ligands 268:278 its ligands 268:278 We have previously reported a 2.0-Å structure of the Vps10 ectodomain in complex with one of its ligands, the tridecapeptide neurotensin. 24985322 7 36 theme 1:1 911:913 arg1 stoichiometry 915:927 a 1:1 stoichiometry 909:927 a 1:1 stoichiometry 909:927 Neurotensin thus appears to bind with a 1:1 stoichiometry, and whereas the N-terminus does not bind on its own, it enhances the affinity in context of full-length neurotensin. 24985322 12 37 with compatible 1709:1718 arg1 insertion 1734:1742 membrane insertion 1725:1742 membrane insertion of the hydrophobic loops 1725:1767 We have, furthermore, mapped all N-linked glycosylations of CHO-expressed human sortilin by mass spectrometry and find that their locations are compatible with membrane insertion of the hydrophobic loops. 24985322 0 38 theme Vps10 32:36 arg1 domain 38:43 the Vps10 domain 28:43 the Vps10 domain of human sortilin 28:61 Revisiting the structure of the Vps10 domain of human sortilin and its interaction with neurotensin. 24985322 0 38 theme Vps10 32:36 arg1 sortilin 54:61 human sortilin 48:61 human sortilin 48:61 Revisiting the structure of the Vps10 domain of human sortilin and its interaction with neurotensin. 24985322 6 39 theme binding 813:819 arg1 experiments 821:831 in vitro binding experiments 804:831 in vitro binding experiments 804:831 However, in vitro binding experiments strongly favor the latter hypothesis. 24985322 12 40 link N-linked 1598:1605 arg1 glycosylations 1607:1620 all N-linked glycosylations 1594:1620 all N-linked glycosylations of CHO-expressed human sortilin 1594:1652 We have, furthermore, mapped all N-linked glycosylations of CHO-expressed human sortilin by mass spectrometry and find that their locations are compatible with membrane insertion of the hydrophobic loops. 24985322 5 41 theme molecule 737:744 arg1 molecule 683:690 a second molecule 674:690 a second molecule of neurotensin 674:705 Here a second peptide fragment was observed within the Vps10 β-propeller, which may in principle either represent a second molecule of neurotensin or the N-terminal part of the molecule bound at the previously identified binding site. 24985322 5 41 theme molecule 737:744 arg1 part 725:728 the N-terminal part 710:728 the N-terminal part of the molecule bound at the previously identified binding site 710:792 Here a second peptide fragment was observed within the Vps10 β-propeller, which may in principle either represent a second molecule of neurotensin or the N-terminal part of the molecule bound at the previously identified binding site. 24985322 5 42 theme second 676:681 arg1 molecule 683:690 a second molecule 674:690 a second molecule of neurotensin 674:705 Here a second peptide fragment was observed within the Vps10 β-propeller, which may in principle either represent a second molecule of neurotensin or the N-terminal part of the molecule bound at the previously identified binding site. 24985322 11 43 theme Vps10 1551:1555 arg1 domain 1557:1562 the Vps10 domain 1547:1562 the Vps10 domain 1547:1562 A computational analysis suggests that this and a neighboring loop may insert into the membrane and thus restrain movement of the Vps10 domain. 24985322 6 44 dep in 804:805 arg1 vitro 807:811 vitro 807:811 vitro 807:811 However, in vitro binding experiments strongly favor the latter hypothesis. 24985322 3 45 with interaction 399:409 arg1 neurotensin 416:426 neurotensin 416:426 neurotensin 416:426 Here we set out to further characterize the structural properties of sortilin and its interaction with neurotensin. 24985322 5 46 theme N-terminal 714:723 arg1 part 725:728 the N-terminal part 710:728 the N-terminal part of the molecule bound at the previously identified binding site 710:792 Here a second peptide fragment was observed within the Vps10 β-propeller, which may in principle either represent a second molecule of neurotensin or the N-terminal part of the molecule bound at the previously identified binding site. 24985322 12 47 theme loops 1763:1767 arg1 insertion 1734:1742 membrane insertion 1725:1742 membrane insertion of the hydrophobic loops 1725:1767 We have, furthermore, mapped all N-linked glycosylations of CHO-expressed human sortilin by mass spectrometry and find that their locations are compatible with membrane insertion of the hydrophobic loops. 24985322 0 48 with structure 15:23 arg1 neurotensin 88:98 neurotensin 88:98 neurotensin 88:98 Revisiting the structure of the Vps10 domain of human sortilin and its interaction with neurotensin. 24985322 11 49 theme computational 1423:1435 arg1 analysis 1437:1444 A computational analysis 1421:1444 A computational analysis 1421:1444 A computational analysis suggests that this and a neighboring loop may insert into the membrane and thus restrain movement of the Vps10 domain. 24985322 3 50 theme sortilin 382:389 arg1 interaction 399:409 its interaction 395:409 its interaction with neurotensin 395:426 Here we set out to further characterize the structural properties of sortilin and its interaction with neurotensin. 24985322 3 50 theme sortilin 382:389 arg1 properties 368:377 the structural properties 353:377 the structural properties of sortilin 353:389 Here we set out to further characterize the structural properties of sortilin and its interaction with neurotensin. 24985322 2 51 with complex 248:254 arg1 neurotensin 300:310 the tridecapeptide neurotensin 281:310 the tridecapeptide neurotensin 281:310 We have previously reported a 2.0-Å structure of the Vps10 ectodomain in complex with one of its ligands, the tridecapeptide neurotensin. 24985322 2 51 with complex 248:254 arg1 one 261:263 one 261:263 one 261:263 We have previously reported a 2.0-Å structure of the Vps10 ectodomain in complex with one of its ligands, the tridecapeptide neurotensin. 24985322 2 51 with complex 248:254 arg1 ligands 272:278 its ligands 268:278 its ligands 268:278 We have previously reported a 2.0-Å structure of the Vps10 ectodomain in complex with one of its ligands, the tridecapeptide neurotensin. 24985322 12 52 theme hydrophobic 1751:1761 arg1 loops 1763:1767 the hydrophobic loops 1747:1767 the hydrophobic loops 1747:1767 We have, furthermore, mapped all N-linked glycosylations of CHO-expressed human sortilin by mass spectrometry and find that their locations are compatible with membrane insertion of the hydrophobic loops. 24985322 2 53 theme 2.0-Å 205:209 arg1 structure 211:219 a 2.0-Å structure 203:219 a 2.0-Å structure of the Vps10 ectodomain in complex with one of its ligands, the tridecapeptide neurotensin 203:310 We have previously reported a 2.0-Å structure of the Vps10 ectodomain in complex with one of its ligands, the tridecapeptide neurotensin. 24985322 12 54 theme mass 1657:1660 arg1 spectrometry 1662:1673 mass spectrometry 1657:1673 mass spectrometry 1657:1673 We have, furthermore, mapped all N-linked glycosylations of CHO-expressed human sortilin by mass spectrometry and find that their locations are compatible with membrane insertion of the hydrophobic loops. 24985322 9 55 theme Crystal 1198:1204 arg1 packing 1206:1212 Crystal packing 1198:1212 Crystal packing 1198:1212 Crystal packing differs partly from the previous structure, which may be due to variations in the degree and pattern of glycosylations. 24985322 9 56 theme previous 1238:1245 arg1 due 1271:1273 due 1271:1273 due 1271:1273 Crystal packing differs partly from the previous structure, which may be due to variations in the degree and pattern of glycosylations. 24985322 9 56 theme previous 1238:1245 arg1 structure 1247:1255 the previous structure 1234:1255 the previous structure 1234:1255 Crystal packing differs partly from the previous structure, which may be due to variations in the degree and pattern of glycosylations. 24985322 1 57 theme multifunctional 115:129 arg1 Sortilin 101:108 Sortilin 101:108 Sortilin 101:108 Sortilin is a multifunctional receptor involved in sorting and apoptosis. 24985322 1 57 theme multifunctional 115:129 arg1 receptor 131:138 a multifunctional receptor 113:138 a multifunctional receptor involved in sorting and apoptosis 113:172 Sortilin is a multifunctional receptor involved in sorting and apoptosis. 24985322 12 58 theme human 1639:1643 arg1 sortilin 1645:1652 CHO-expressed human sortilin 1625:1652 CHO-expressed human sortilin 1625:1652 We have, furthermore, mapped all N-linked glycosylations of CHO-expressed human sortilin by mass spectrometry and find that their locations are compatible with membrane insertion of the hydrophobic loops. 24985322 0 59 theme sortilin 54:61 arg1 domain 38:43 the Vps10 domain 28:43 the Vps10 domain of human sortilin 28:61 Revisiting the structure of the Vps10 domain of human sortilin and its interaction with neurotensin. 24985322 0 59 theme sortilin 54:61 arg1 sortilin 54:61 human sortilin 48:61 human sortilin 48:61 Revisiting the structure of the Vps10 domain of human sortilin and its interaction with neurotensin. 24985322 5 60 located observed 595:602 arg2 fragment 582:589 a second peptide fragment 565:589 a second peptide fragment 565:589 Here a second peptide fragment was observed within the Vps10 β-propeller, which may in principle either represent a second molecule of neurotensin or the N-terminal part of the molecule bound at the previously identified binding site. 24985322 5 60 located observed 595:602 arg1 β-propeller 621:631 the Vps10 β-propeller 611:631 the Vps10 β-propeller 611:631 Here a second peptide fragment was observed within the Vps10 β-propeller, which may in principle either represent a second molecule of neurotensin or the N-terminal part of the molecule bound at the previously identified binding site. 24985322 2 61 theme ectodomain 234:243 arg1 structure 211:219 a 2.0-Å structure 203:219 a 2.0-Å structure of the Vps10 ectodomain in complex with one of its ligands, the tridecapeptide neurotensin 203:310 We have previously reported a 2.0-Å structure of the Vps10 ectodomain in complex with one of its ligands, the tridecapeptide neurotensin. 24985322 12 62 theme CHO-expressed 1625:1637 arg1 sortilin 1645:1652 CHO-expressed human sortilin 1625:1652 CHO-expressed human sortilin 1625:1652 We have, furthermore, mapped all N-linked glycosylations of CHO-expressed human sortilin by mass spectrometry and find that their locations are compatible with membrane insertion of the hydrophobic loops. 24985322 9 63 theme glycosylations 1318:1331 arg1 pattern 1307:1313 pattern 1307:1313 pattern 1307:1313 Crystal packing differs partly from the previous structure, which may be due to variations in the degree and pattern of glycosylations. 24985322 9 63 theme glycosylations 1318:1331 arg1 degree 1296:1301 degree 1296:1301 degree 1296:1301 Crystal packing differs partly from the previous structure, which may be due to variations in the degree and pattern of glycosylations. 24985322 0 64 theme human 48:52 arg1 sortilin 54:61 human sortilin 48:61 human sortilin 48:61 Revisiting the structure of the Vps10 domain of human sortilin and its interaction with neurotensin. 24985322 11 65 theme domain 1557:1562 arg1 movement 1535:1542 movement 1535:1542 movement of the Vps10 domain 1535:1562 A computational analysis suggests that this and a neighboring loop may insert into the membrane and thus restrain movement of the Vps10 domain. 24985322 2 66 theme Vps10 228:232 arg1 ectodomain 234:243 the Vps10 ectodomain 224:243 the Vps10 ectodomain 224:243 We have previously reported a 2.0-Å structure of the Vps10 ectodomain in complex with one of its ligands, the tridecapeptide neurotensin. 25096878 3 0 theme live 208:211 arg1 cells 202:206 Biofilm cells live 194:211 Biofilm cells live 194:211 Biofilm cells live immersed in a self-produced matrix, a blend of extracellular biopolymers, many of which are uncharacterized. 25096878 8 1 theme functional 878:887 arg1 importance 889:898 functional importance 878:898 functional importance 878:898 Surprisingly, a previously identified polysaccharide of functional importance, β-1,3-glucan, comprised only a small portion of the total matrix carbohydrate. 25096878 14 2 theme Nuclear 1602:1608 arg1 NMR 1630:1632 NMR 1630:1632 NMR 1630:1632 Nuclear magnetic resonance (NMR) analysis demonstrated interaction of aggregate matrix with the antifungal fluconazole, consistent with a role in drug impedance and contribution of multiple matrix components. 25096878 14 2 theme Nuclear 1602:1608 arg1 resonance 1619:1627 Nuclear magnetic resonance 1602:1627 Nuclear magnetic resonance (NMR) analysis 1602:1642 Nuclear magnetic resonance (NMR) analysis demonstrated interaction of aggregate matrix with the antifungal fluconazole, consistent with a role in drug impedance and contribution of multiple matrix components. 25096878 3 3 theme Biofilm 194:200 arg1 cells 202:206 Biofilm cells live 194:211 Biofilm cells live 194:211 Biofilm cells live immersed in a self-produced matrix, a blend of extracellular biopolymers, many of which are uncharacterized. 25096878 4 4 theme comprehensive 350:362 arg1 analysis 364:371 a comprehensive analysis 348:371 a comprehensive analysis of the matrix manufactured by Candida albicans both in vitro and in a clinical niche animal model 348:469 In this study, we provide a comprehensive analysis of the matrix manufactured by Candida albicans both in vitro and in a clinical niche animal model. 25096878 4 5 dep albicans 411:418 arg1 both 420:423 both 420:423 both 420:423 In this study, we provide a comprehensive analysis of the matrix manufactured by Candida albicans both in vitro and in a clinical niche animal model. 25096878 4 5 dep albicans 411:418 arg1 model 465:469 a clinical niche animal model 441:469 a clinical niche animal model 441:469 In this study, we provide a comprehensive analysis of the matrix manufactured by Candida albicans both in vitro and in a clinical niche animal model. 25096878 3 6 theme self-produced 227:239 arg1 blend 251:255 a blend 249:255 a blend of extracellular biopolymers, many of which are uncharacterized 249:319 Biofilm cells live immersed in a self-produced matrix, a blend of extracellular biopolymers, many of which are uncharacterized. 25096878 3 6 theme self-produced 227:239 arg1 matrix 241:246 a self-produced matrix 225:246 a self-produced matrix 225:246 Biofilm cells live immersed in a self-produced matrix, a blend of extracellular biopolymers, many of which are uncharacterized. 25096878 14 7 theme magnetic 1610:1617 arg1 NMR 1630:1632 NMR 1630:1632 NMR 1630:1632 Nuclear magnetic resonance (NMR) analysis demonstrated interaction of aggregate matrix with the antifungal fluconazole, consistent with a role in drug impedance and contribution of multiple matrix components. 25096878 14 7 theme magnetic 1610:1617 arg1 resonance 1619:1627 Nuclear magnetic resonance 1602:1627 Nuclear magnetic resonance (NMR) analysis 1602:1642 Nuclear magnetic resonance (NMR) analysis demonstrated interaction of aggregate matrix with the antifungal fluconazole, consistent with a role in drug impedance and contribution of multiple matrix components. 25096878 7 8 theme individual 736:745 arg1 polysaccharides 747:761 Three individual polysaccharides 730:761 Three individual polysaccharides 730:761 Three individual polysaccharides were identified and were suggested to interact physically. 25096878 14 9 theme matrix 1792:1797 arg1 components 1799:1808 multiple matrix components 1783:1808 multiple matrix components 1783:1808 Nuclear magnetic resonance (NMR) analysis demonstrated interaction of aggregate matrix with the antifungal fluconazole, consistent with a role in drug impedance and contribution of multiple matrix components. 25096878 13 10 dep in 1585:1586 arg1 vivo 1588:1591 vivo 1588:1591 vivo 1588:1591 Several of the in vitro matrix components, including proteins and each of the polysaccharides, were also present in the matrix of a clinically relevant in vivo biofilm. 25096878 9 11 dep described 986:994 arg1 abundant 1002:1009 abundant 1002:1009 abundant 1002:1009 Newly described, more abundant polysaccharides included α-1,2 branched α-1,6-mannans (87%) associated with unbranched β-1,6-glucans (13%) in an apparent mannan-glucan complex (MGCx). 25096878 11 12 theme neutral 1265:1271 arg1 glycerolipids 1273:1285 neutral glycerolipids 1265:1285 neutral glycerolipids (89.1%) 1265:1293 The matrix lipids consisted of neutral glycerolipids (89.1%), polar glycerolipids (10.4%), and sphingolipids (0.5%). 25096878 11 12 theme neutral 1265:1271 arg1 % 1292:1292 89.1% 1288:1292 89.1% 1288:1292 The matrix lipids consisted of neutral glycerolipids (89.1%), polar glycerolipids (10.4%), and sphingolipids (0.5%). 25096878 6 13 theme nucleic 681:687 arg1 acid 689:692 5% nucleic acid 678:692 5% nucleic acid 678:692 We uncovered components from each of the macromolecular classes (55% protein, 25% carbohydrate, 15% lipid, and 5% nucleic acid) in the C. albicans biofilm matrix. 25096878 6 13 theme nucleic 681:687 arg1 classes 623:629 the macromolecular classes 604:629 the macromolecular classes (55% protein, 25% carbohydrate, 15% lipid, and 5% nucleic acid) 604:693 We uncovered components from each of the macromolecular classes (55% protein, 25% carbohydrate, 15% lipid, and 5% nucleic acid) in the C. albicans biofilm matrix. 25096878 13 14 theme matrix 1457:1462 arg1 components 1464:1473 the in vitro matrix components 1444:1473 the in vitro matrix components 1444:1473 Several of the in vitro matrix components, including proteins and each of the polysaccharides, were also present in the matrix of a clinically relevant in vivo biofilm. 25096878 13 14 theme matrix 1457:1462 arg1 proteins 1486:1493 proteins 1486:1493 proteins 1486:1493 Several of the in vitro matrix components, including proteins and each of the polysaccharides, were also present in the matrix of a clinically relevant in vivo biofilm. 25096878 13 14 theme matrix 1457:1462 arg1 polysaccharides 1511:1525 the polysaccharides 1507:1525 the polysaccharides 1507:1525 Several of the in vitro matrix components, including proteins and each of the polysaccharides, were also present in the matrix of a clinically relevant in vivo biofilm. 25096878 13 14 theme matrix 1457:1462 arg1 each 1499:1502 each 1499:1502 each 1499:1502 Several of the in vitro matrix components, including proteins and each of the polysaccharides, were also present in the matrix of a clinically relevant in vivo biofilm. 25096878 8 15 theme small 932:936 arg1 portion 938:944 a small portion 930:944 a small portion of the total matrix carbohydrate 930:977 Surprisingly, a previously identified polysaccharide of functional importance, β-1,3-glucan, comprised only a small portion of the total matrix carbohydrate. 25096878 14 16 from contribution 1767:1778 arg1 impedance 1753:1761 drug impedance 1748:1761 drug impedance 1748:1761 Nuclear magnetic resonance (NMR) analysis demonstrated interaction of aggregate matrix with the antifungal fluconazole, consistent with a role in drug impedance and contribution of multiple matrix components. 25096878 6 17 dep C. 702:703 arg1 albicans 705:712 albicans 705:712 albicans 705:712 We uncovered components from each of the macromolecular classes (55% protein, 25% carbohydrate, 15% lipid, and 5% nucleic acid) in the C. albicans biofilm matrix. 25096878 14 18 theme drug 1748:1751 arg1 impedance 1753:1761 drug impedance 1748:1761 drug impedance 1748:1761 Nuclear magnetic resonance (NMR) analysis demonstrated interaction of aggregate matrix with the antifungal fluconazole, consistent with a role in drug impedance and contribution of multiple matrix components. 25096878 13 19 theme in 1448:1449 arg1 components 1464:1473 the in vitro matrix components 1444:1473 the in vitro matrix components 1444:1473 Several of the in vitro matrix components, including proteins and each of the polysaccharides, were also present in the matrix of a clinically relevant in vivo biofilm. 25096878 13 19 theme in 1448:1449 arg1 proteins 1486:1493 proteins 1486:1493 proteins 1486:1493 Several of the in vitro matrix components, including proteins and each of the polysaccharides, were also present in the matrix of a clinically relevant in vivo biofilm. 25096878 13 19 theme in 1448:1449 arg1 polysaccharides 1511:1525 the polysaccharides 1507:1525 the polysaccharides 1507:1525 Several of the in vitro matrix components, including proteins and each of the polysaccharides, were also present in the matrix of a clinically relevant in vivo biofilm. 25096878 13 19 theme in 1448:1449 arg1 each 1499:1502 each 1499:1502 each 1499:1502 Several of the in vitro matrix components, including proteins and each of the polysaccharides, were also present in the matrix of a clinically relevant in vivo biofilm. 25096878 5 20 theme matrix 507:512 arg1 impact 540:545 the impact 536:545 the impact on drug resistance 536:564 We further explore the function of matrix components, including the impact on drug resistance. 25096878 5 20 theme matrix 507:512 arg1 components 514:523 matrix components 507:523 matrix components 507:523 We further explore the function of matrix components, including the impact on drug resistance. 25096878 5 21 from impact 540:545 arg1 resistance 555:564 drug resistance 550:564 drug resistance 550:564 We further explore the function of matrix components, including the impact on drug resistance. 25096878 3 22 theme extracellular 260:272 arg1 biopolymers 274:284 extracellular biopolymers 260:284 extracellular biopolymers 260:284 Biofilm cells live immersed in a self-produced matrix, a blend of extracellular biopolymers, many of which are uncharacterized. 25096878 4 23 theme matrix 380:385 arg1 analysis 364:371 a comprehensive analysis 348:371 a comprehensive analysis of the matrix manufactured by Candida albicans both in vitro and in a clinical niche animal model 348:469 In this study, we provide a comprehensive analysis of the matrix manufactured by Candida albicans both in vitro and in a clinical niche animal model. 25096878 16 24 theme defining 2224:2231 arg1 trait 2233:2237 a defining trait 2222:2237 a defining trait of this lifestyle 2222:2255 The availability of these biochemical analyses provides a unique resource for further functional investigation of the biofilm matrix, a defining trait of this lifestyle. 25096878 16 24 theme defining 2224:2231 arg1 investigation 2185:2197 further functional investigation 2166:2197 further functional investigation of the biofilm matrix 2166:2219 The availability of these biochemical analyses provides a unique resource for further functional investigation of the biofilm matrix, a defining trait of this lifestyle. 25096878 16 25 theme functional 2174:2183 arg1 investigation 2185:2197 further functional investigation 2166:2197 further functional investigation of the biofilm matrix 2166:2219 The availability of these biochemical analyses provides a unique resource for further functional investigation of the biofilm matrix, a defining trait of this lifestyle. 25096878 16 25 theme functional 2174:2183 arg1 trait 2233:2237 a defining trait 2222:2237 a defining trait of this lifestyle 2222:2255 The availability of these biochemical analyses provides a unique resource for further functional investigation of the biofilm matrix, a defining trait of this lifestyle. 25096878 13 26 attach present 1538:1544 arg2 Several 1433:1439 Several 1433:1439 Several 1433:1439 Several of the in vitro matrix components, including proteins and each of the polysaccharides, were also present in the matrix of a clinically relevant in vivo biofilm. 25096878 13 26 attach present 1538:1544 arg1 matrix 1553:1558 the matrix 1549:1558 the matrix of a clinically relevant in vivo biofilm 1549:1599 Several of the in vitro matrix components, including proteins and each of the polysaccharides, were also present in the matrix of a clinically relevant in vivo biofilm. 25096878 16 27 theme matrix 2214:2219 arg1 investigation 2185:2197 further functional investigation 2166:2197 further functional investigation of the biofilm matrix 2166:2219 The availability of these biochemical analyses provides a unique resource for further functional investigation of the biofilm matrix, a defining trait of this lifestyle. 25096878 16 27 theme matrix 2214:2219 arg1 trait 2233:2237 a defining trait 2222:2237 a defining trait of this lifestyle 2222:2255 The availability of these biochemical analyses provides a unique resource for further functional investigation of the biofilm matrix, a defining trait of this lifestyle. 25096878 14 28 with consistent 1722:1731 arg1 contribution 1767:1778 contribution 1767:1778 contribution of multiple matrix components 1767:1808 Nuclear magnetic resonance (NMR) analysis demonstrated interaction of aggregate matrix with the antifungal fluconazole, consistent with a role in drug impedance and contribution of multiple matrix components. 25096878 14 28 with consistent 1722:1731 arg1 role 1740:1743 a role 1738:1743 a role in drug impedance 1738:1761 Nuclear magnetic resonance (NMR) analysis demonstrated interaction of aggregate matrix with the antifungal fluconazole, consistent with a role in drug impedance and contribution of multiple matrix components. 25096878 4 29 theme niche 452:456 arg1 model 465:469 a clinical niche animal model 441:469 a clinical niche animal model 441:469 In this study, we provide a comprehensive analysis of the matrix manufactured by Candida albicans both in vitro and in a clinical niche animal model. 25096878 10 30 theme matrix 1174:1179 arg1 analysis 1191:1198 Functional matrix proteomic analysis 1163:1198 Functional matrix proteomic analysis 1163:1198 Functional matrix proteomic analysis revealed 458 distinct activities. 25096878 14 31 theme antifungal 1698:1707 arg1 fluconazole 1709:1719 the antifungal fluconazole 1694:1719 the antifungal fluconazole 1694:1719 Nuclear magnetic resonance (NMR) analysis demonstrated interaction of aggregate matrix with the antifungal fluconazole, consistent with a role in drug impedance and contribution of multiple matrix components. 25096878 6 32 dep classes 623:629 arg1 acid 689:692 5% nucleic acid 678:692 5% nucleic acid 678:692 We uncovered components from each of the macromolecular classes (55% protein, 25% carbohydrate, 15% lipid, and 5% nucleic acid) in the C. albicans biofilm matrix. 25096878 6 32 dep classes 623:629 arg1 carbohydrate 649:660 25% carbohydrate 645:660 25% carbohydrate 645:660 We uncovered components from each of the macromolecular classes (55% protein, 25% carbohydrate, 15% lipid, and 5% nucleic acid) in the C. albicans biofilm matrix. 25096878 6 32 dep classes 623:629 arg1 protein 636:642 55% protein 632:642 55% protein 632:642 We uncovered components from each of the macromolecular classes (55% protein, 25% carbohydrate, 15% lipid, and 5% nucleic acid) in the C. albicans biofilm matrix. 25096878 6 32 dep classes 623:629 arg1 lipid 667:671 15% lipid 663:671 15% lipid 663:671 We uncovered components from each of the macromolecular classes (55% protein, 25% carbohydrate, 15% lipid, and 5% nucleic acid) in the C. albicans biofilm matrix. 25096878 6 32 dep classes 623:629 arg1 classes 623:629 the macromolecular classes 604:629 the macromolecular classes (55% protein, 25% carbohydrate, 15% lipid, and 5% nucleic acid) 604:693 We uncovered components from each of the macromolecular classes (55% protein, 25% carbohydrate, 15% lipid, and 5% nucleic acid) in the C. albicans biofilm matrix. 25096878 9 33 theme described 986:994 arg1 polysaccharides 1011:1025 Newly described, more abundant polysaccharides 980:1025 Newly described, more abundant polysaccharides 980:1025 Newly described, more abundant polysaccharides included α-1,2 branched α-1,6-mannans (87%) associated with unbranched β-1,6-glucans (13%) in an apparent mannan-glucan complex (MGCx). 25096878 8 34 theme total 953:957 arg1 carbohydrate 966:977 the total matrix carbohydrate 949:977 the total matrix carbohydrate 949:977 Surprisingly, a previously identified polysaccharide of functional importance, β-1,3-glucan, comprised only a small portion of the total matrix carbohydrate. 25096878 16 35 theme further 2166:2172 arg1 investigation 2185:2197 further functional investigation 2166:2197 further functional investigation of the biofilm matrix 2166:2219 The availability of these biochemical analyses provides a unique resource for further functional investigation of the biofilm matrix, a defining trait of this lifestyle. 25096878 16 35 theme further 2166:2172 arg1 trait 2233:2237 a defining trait 2222:2237 a defining trait of this lifestyle 2222:2255 The availability of these biochemical analyses provides a unique resource for further functional investigation of the biofilm matrix, a defining trait of this lifestyle. 25096878 6 36 theme 25 645:646 arg1 % 647:647 % 647:647 % 647:647 We uncovered components from each of the macromolecular classes (55% protein, 25% carbohydrate, 15% lipid, and 5% nucleic acid) in the C. albicans biofilm matrix. 25096878 8 37 theme carbohydrate 966:977 arg1 portion 938:944 a small portion 930:944 a small portion of the total matrix carbohydrate 930:977 Surprisingly, a previously identified polysaccharide of functional importance, β-1,3-glucan, comprised only a small portion of the total matrix carbohydrate. 25096878 1 38 theme Candida 68:74 arg1 Virulence 55:63 Virulence 55:63 Virulence of Candida 55:74 Virulence of Candida is linked with its ability to form biofilms. 25096878 13 39 dep in 1448:1449 arg1 vitro 1451:1455 vitro 1451:1455 vitro 1451:1455 Several of the in vitro matrix components, including proteins and each of the polysaccharides, were also present in the matrix of a clinically relevant in vivo biofilm. 25096878 13 40 from matrix 1553:1558 arg1 present 1538:1544 present 1538:1544 present 1538:1544 Several of the in vitro matrix components, including proteins and each of the polysaccharides, were also present in the matrix of a clinically relevant in vivo biofilm. 25096878 14 41 with interaction 1657:1667 arg1 fluconazole 1709:1719 the antifungal fluconazole 1694:1719 the antifungal fluconazole 1694:1719 Nuclear magnetic resonance (NMR) analysis demonstrated interaction of aggregate matrix with the antifungal fluconazole, consistent with a role in drug impedance and contribution of multiple matrix components. 25096878 15 42 theme biofilm 1925:1931 arg1 matrix 1933:1938 the Candida biofilm matrix 1913:1938 the Candida biofilm matrix 1913:1938 Importance: This report is the first to decipher the complex and unique macromolecular composition of the Candida biofilm matrix, demonstrate the clinical relevance of matrix components, and show that multiple matrix components are needed for protection from antifungal drugs. 25096878 15 43 theme macromolecular 1883:1896 arg1 composition 1898:1908 the complex and unique macromolecular composition 1860:1908 the complex and unique macromolecular composition of the Candida biofilm matrix 1860:1938 Importance: This report is the first to decipher the complex and unique macromolecular composition of the Candida biofilm matrix, demonstrate the clinical relevance of matrix components, and show that multiple matrix components are needed for protection from antifungal drugs. 25096878 6 44 theme 55 632:633 arg1 % 634:634 % 634:634 % 634:634 We uncovered components from each of the macromolecular classes (55% protein, 25% carbohydrate, 15% lipid, and 5% nucleic acid) in the C. albicans biofilm matrix. 25096878 14 45 theme matrix 1682:1687 arg1 interaction 1657:1667 interaction 1657:1667 interaction of aggregate matrix with the antifungal fluconazole, consistent with a role in drug impedance and contribution of multiple matrix components 1657:1808 Nuclear magnetic resonance (NMR) analysis demonstrated interaction of aggregate matrix with the antifungal fluconazole, consistent with a role in drug impedance and contribution of multiple matrix components. 25096878 0 46 theme fungal 19:24 arg1 encyclopedia 41:52 a fungal biofilm matrix encyclopedia 17:52 a fungal biofilm matrix encyclopedia 17:52 Novel entries in a fungal biofilm matrix encyclopedia. 25096878 2 47 theme biofilm 139:145 arg1 infections 147:156 biofilm infections 139:156 biofilm infections 139:156 Once established, biofilm infections are nearly impossible to eradicate. 25096878 0 48 theme matrix 34:39 arg1 encyclopedia 41:52 a fungal biofilm matrix encyclopedia 17:52 a fungal biofilm matrix encyclopedia 17:52 Novel entries in a fungal biofilm matrix encyclopedia. 25096878 8 49 theme identified 849:858 arg1 β-1,3-glucan 901:912 β-1,3-glucan 901:912 β-1,3-glucan 901:912 Surprisingly, a previously identified polysaccharide of functional importance, β-1,3-glucan, comprised only a small portion of the total matrix carbohydrate. 25096878 8 49 theme identified 849:858 arg1 polysaccharide 860:873 a previously identified polysaccharide 836:873 a previously identified polysaccharide of functional importance 836:898 Surprisingly, a previously identified polysaccharide of functional importance, β-1,3-glucan, comprised only a small portion of the total matrix carbohydrate. 25096878 12 50 theme nucleic 1373:1379 arg1 acid 1381:1384 matrix nucleic acid 1366:1384 matrix nucleic acid 1366:1384 Examination of matrix nucleic acid identified DNA, primarily noncoding sequences. 25096878 15 51 theme matrix 1979:1984 arg1 components 1986:1995 matrix components 1979:1995 matrix components 1979:1995 Importance: This report is the first to decipher the complex and unique macromolecular composition of the Candida biofilm matrix, demonstrate the clinical relevance of matrix components, and show that multiple matrix components are needed for protection from antifungal drugs. 25096878 13 52 located present 1538:1544 arg1 matrix 1553:1558 the matrix 1549:1558 the matrix of a clinically relevant in vivo biofilm 1549:1599 Several of the in vitro matrix components, including proteins and each of the polysaccharides, were also present in the matrix of a clinically relevant in vivo biofilm. 25096878 13 52 located present 1538:1544 arg2 Several 1433:1439 Several 1433:1439 Several 1433:1439 Several of the in vitro matrix components, including proteins and each of the polysaccharides, were also present in the matrix of a clinically relevant in vivo biofilm. 25096878 11 53 theme polar 1296:1300 arg1 glycerolipids 1302:1314 polar glycerolipids 1296:1314 polar glycerolipids (10.4%) 1296:1322 The matrix lipids consisted of neutral glycerolipids (89.1%), polar glycerolipids (10.4%), and sphingolipids (0.5%). 25096878 11 53 theme polar 1296:1300 arg1 % 1321:1321 10.4% 1317:1321 10.4% 1317:1321 The matrix lipids consisted of neutral glycerolipids (89.1%), polar glycerolipids (10.4%), and sphingolipids (0.5%). 25096878 6 54 theme 15 663:664 arg1 % 665:665 % 665:665 % 665:665 We uncovered components from each of the macromolecular classes (55% protein, 25% carbohydrate, 15% lipid, and 5% nucleic acid) in the C. albicans biofilm matrix. 25096878 14 55 from role 1740:1743 arg1 impedance 1753:1761 drug impedance 1748:1761 drug impedance 1748:1761 Nuclear magnetic resonance (NMR) analysis demonstrated interaction of aggregate matrix with the antifungal fluconazole, consistent with a role in drug impedance and contribution of multiple matrix components. 25096878 8 56 theme importance 889:898 arg1 β-1,3-glucan 901:912 β-1,3-glucan 901:912 β-1,3-glucan 901:912 Surprisingly, a previously identified polysaccharide of functional importance, β-1,3-glucan, comprised only a small portion of the total matrix carbohydrate. 25096878 8 56 theme importance 889:898 arg1 polysaccharide 860:873 a previously identified polysaccharide 836:873 a previously identified polysaccharide of functional importance 836:898 Surprisingly, a previously identified polysaccharide of functional importance, β-1,3-glucan, comprised only a small portion of the total matrix carbohydrate. 25096878 13 57 from present 1538:1544 arg1 matrix 1553:1558 the matrix 1549:1558 the matrix of a clinically relevant in vivo biofilm 1549:1599 Several of the in vitro matrix components, including proteins and each of the polysaccharides, were also present in the matrix of a clinically relevant in vivo biofilm. 25096878 16 58 theme analyses 2126:2133 arg1 availability 2092:2103 The availability 2088:2103 The availability of these biochemical analyses 2088:2133 The availability of these biochemical analyses provides a unique resource for further functional investigation of the biofilm matrix, a defining trait of this lifestyle. 25096878 6 59 theme C. 702:703 arg1 matrix 722:727 the C. albicans biofilm matrix 698:727 the C. albicans biofilm matrix 698:727 We uncovered components from each of the macromolecular classes (55% protein, 25% carbohydrate, 15% lipid, and 5% nucleic acid) in the C. albicans biofilm matrix. 25096878 4 60 dep both 420:423 arg1 vitro 428:432 vitro 428:432 vitro 428:432 In this study, we provide a comprehensive analysis of the matrix manufactured by Candida albicans both in vitro and in a clinical niche animal model. 25096878 16 61 theme biofilm 2206:2212 arg1 matrix 2214:2219 the biofilm matrix 2202:2219 the biofilm matrix 2202:2219 The availability of these biochemical analyses provides a unique resource for further functional investigation of the biofilm matrix, a defining trait of this lifestyle. 25096878 14 62 theme components 1799:1808 arg1 contribution 1767:1778 contribution 1767:1778 contribution of multiple matrix components 1767:1808 Nuclear magnetic resonance (NMR) analysis demonstrated interaction of aggregate matrix with the antifungal fluconazole, consistent with a role in drug impedance and contribution of multiple matrix components. 25096878 14 62 theme components 1799:1808 arg1 role 1740:1743 a role 1738:1743 a role in drug impedance 1738:1761 Nuclear magnetic resonance (NMR) analysis demonstrated interaction of aggregate matrix with the antifungal fluconazole, consistent with a role in drug impedance and contribution of multiple matrix components. 25096878 9 63 from β-1,6-glucans 1098:1110 arg1 MGCx 1156:1159 MGCx 1156:1159 MGCx 1156:1159 Newly described, more abundant polysaccharides included α-1,2 branched α-1,6-mannans (87%) associated with unbranched β-1,6-glucans (13%) in an apparent mannan-glucan complex (MGCx). 25096878 9 63 from β-1,6-glucans 1098:1110 arg1 complex 1147:1153 an apparent mannan-glucan complex 1121:1153 an apparent mannan-glucan complex (MGCx) 1121:1160 Newly described, more abundant polysaccharides included α-1,2 branched α-1,6-mannans (87%) associated with unbranched β-1,6-glucans (13%) in an apparent mannan-glucan complex (MGCx). 25096878 16 64 theme lifestyle 2247:2255 arg1 trait 2233:2237 a defining trait 2222:2237 a defining trait of this lifestyle 2222:2255 The availability of these biochemical analyses provides a unique resource for further functional investigation of the biofilm matrix, a defining trait of this lifestyle. 25096878 16 64 theme lifestyle 2247:2255 arg1 investigation 2185:2197 further functional investigation 2166:2197 further functional investigation of the biofilm matrix 2166:2219 The availability of these biochemical analyses provides a unique resource for further functional investigation of the biofilm matrix, a defining trait of this lifestyle. 25096878 14 65 theme multiple 1783:1790 arg1 components 1799:1808 multiple matrix components 1783:1808 multiple matrix components 1783:1808 Nuclear magnetic resonance (NMR) analysis demonstrated interaction of aggregate matrix with the antifungal fluconazole, consistent with a role in drug impedance and contribution of multiple matrix components. 25096878 9 66 theme apparent 1124:1131 arg1 MGCx 1156:1159 MGCx 1156:1159 MGCx 1156:1159 Newly described, more abundant polysaccharides included α-1,2 branched α-1,6-mannans (87%) associated with unbranched β-1,6-glucans (13%) in an apparent mannan-glucan complex (MGCx). 25096878 9 66 theme apparent 1124:1131 arg1 complex 1147:1153 an apparent mannan-glucan complex 1121:1153 an apparent mannan-glucan complex (MGCx) 1121:1160 Newly described, more abundant polysaccharides included α-1,2 branched α-1,6-mannans (87%) associated with unbranched β-1,6-glucans (13%) in an apparent mannan-glucan complex (MGCx). 25096878 6 67 theme % 679:679 arg1 acid 689:692 5% nucleic acid 678:692 5% nucleic acid 678:692 We uncovered components from each of the macromolecular classes (55% protein, 25% carbohydrate, 15% lipid, and 5% nucleic acid) in the C. albicans biofilm matrix. 25096878 6 67 theme % 679:679 arg1 classes 623:629 the macromolecular classes 604:629 the macromolecular classes (55% protein, 25% carbohydrate, 15% lipid, and 5% nucleic acid) 604:693 We uncovered components from each of the macromolecular classes (55% protein, 25% carbohydrate, 15% lipid, and 5% nucleic acid) in the C. albicans biofilm matrix. 25096878 13 68 theme components 1464:1473 arg1 Several 1433:1439 Several 1433:1439 Several 1433:1439 Several of the in vitro matrix components, including proteins and each of the polysaccharides, were also present in the matrix of a clinically relevant in vivo biofilm. 25096878 15 69 theme matrix 2021:2026 arg1 components 2028:2037 multiple matrix components 2012:2037 multiple matrix components 2012:2037 Importance: This report is the first to decipher the complex and unique macromolecular composition of the Candida biofilm matrix, demonstrate the clinical relevance of matrix components, and show that multiple matrix components are needed for protection from antifungal drugs. 25096878 13 70 dep relevant 1576:1583 arg1 in 1585:1586 in 1585:1586 in 1585:1586 Several of the in vitro matrix components, including proteins and each of the polysaccharides, were also present in the matrix of a clinically relevant in vivo biofilm. 25096878 15 71 theme antifungal 2070:2079 arg1 drugs 2081:2085 antifungal drugs 2070:2085 antifungal drugs 2070:2085 Importance: This report is the first to decipher the complex and unique macromolecular composition of the Candida biofilm matrix, demonstrate the clinical relevance of matrix components, and show that multiple matrix components are needed for protection from antifungal drugs. 25096878 13 72 theme biofilm 1593:1599 arg1 matrix 1553:1558 the matrix 1549:1558 the matrix of a clinically relevant in vivo biofilm 1549:1599 Several of the in vitro matrix components, including proteins and each of the polysaccharides, were also present in the matrix of a clinically relevant in vivo biofilm. 25096878 6 73 from each 596:599 arg1 components 580:589 components 580:589 components from each of the macromolecular classes (55% protein, 25% carbohydrate, 15% lipid, and 5% nucleic acid) 580:693 We uncovered components from each of the macromolecular classes (55% protein, 25% carbohydrate, 15% lipid, and 5% nucleic acid) in the C. albicans biofilm matrix. 25096878 15 74 theme multiple 2012:2019 arg1 components 2028:2037 multiple matrix components 2012:2037 multiple matrix components 2012:2037 Importance: This report is the first to decipher the complex and unique macromolecular composition of the Candida biofilm matrix, demonstrate the clinical relevance of matrix components, and show that multiple matrix components are needed for protection from antifungal drugs. 25096878 6 75 theme macromolecular 608:621 arg1 acid 689:692 5% nucleic acid 678:692 5% nucleic acid 678:692 We uncovered components from each of the macromolecular classes (55% protein, 25% carbohydrate, 15% lipid, and 5% nucleic acid) in the C. albicans biofilm matrix. 25096878 6 75 theme macromolecular 608:621 arg1 classes 623:629 the macromolecular classes 604:629 the macromolecular classes (55% protein, 25% carbohydrate, 15% lipid, and 5% nucleic acid) 604:693 We uncovered components from each of the macromolecular classes (55% protein, 25% carbohydrate, 15% lipid, and 5% nucleic acid) in the C. albicans biofilm matrix. 25096878 6 75 theme macromolecular 608:621 arg1 protein 636:642 55% protein 632:642 55% protein 632:642 We uncovered components from each of the macromolecular classes (55% protein, 25% carbohydrate, 15% lipid, and 5% nucleic acid) in the C. albicans biofilm matrix. 25096878 6 75 theme macromolecular 608:621 arg1 carbohydrate 649:660 25% carbohydrate 645:660 25% carbohydrate 645:660 We uncovered components from each of the macromolecular classes (55% protein, 25% carbohydrate, 15% lipid, and 5% nucleic acid) in the C. albicans biofilm matrix. 25096878 6 75 theme macromolecular 608:621 arg1 lipid 667:671 15% lipid 663:671 15% lipid 663:671 We uncovered components from each of the macromolecular classes (55% protein, 25% carbohydrate, 15% lipid, and 5% nucleic acid) in the C. albicans biofilm matrix. 25096878 9 76 theme mannan-glucan 1133:1145 arg1 MGCx 1156:1159 MGCx 1156:1159 MGCx 1156:1159 Newly described, more abundant polysaccharides included α-1,2 branched α-1,6-mannans (87%) associated with unbranched β-1,6-glucans (13%) in an apparent mannan-glucan complex (MGCx). 25096878 9 76 theme mannan-glucan 1133:1145 arg1 complex 1147:1153 an apparent mannan-glucan complex 1121:1153 an apparent mannan-glucan complex (MGCx) 1121:1160 Newly described, more abundant polysaccharides included α-1,2 branched α-1,6-mannans (87%) associated with unbranched β-1,6-glucans (13%) in an apparent mannan-glucan complex (MGCx). 25096878 5 77 theme components 514:523 arg1 function 495:502 the function 491:502 the function of matrix components, including the impact on drug resistance 491:564 We further explore the function of matrix components, including the impact on drug resistance. 25096878 3 78 theme biopolymers 274:284 arg1 blend 251:255 a blend 249:255 a blend of extracellular biopolymers, many of which are uncharacterized 249:319 Biofilm cells live immersed in a self-produced matrix, a blend of extracellular biopolymers, many of which are uncharacterized. 25096878 3 78 theme biopolymers 274:284 arg1 biopolymers 274:284 extracellular biopolymers 260:284 extracellular biopolymers 260:284 Biofilm cells live immersed in a self-produced matrix, a blend of extracellular biopolymers, many of which are uncharacterized. 25096878 3 78 theme biopolymers 274:284 arg1 matrix 241:246 a self-produced matrix 225:246 a self-produced matrix 225:246 Biofilm cells live immersed in a self-produced matrix, a blend of extracellular biopolymers, many of which are uncharacterized. 25096878 3 78 theme biopolymers 274:284 arg1 many 287:290 many 287:290 many 287:290 Biofilm cells live immersed in a self-produced matrix, a blend of extracellular biopolymers, many of which are uncharacterized. 25096878 4 79 theme Candida 403:409 arg1 albicans 411:418 Candida albicans 403:418 Candida albicans both in vitro and in a clinical niche animal model 403:469 In this study, we provide a comprehensive analysis of the matrix manufactured by Candida albicans both in vitro and in a clinical niche animal model. 25096878 14 80 theme consistent 1722:1731 arg1 fluconazole 1709:1719 the antifungal fluconazole 1694:1719 the antifungal fluconazole 1694:1719 Nuclear magnetic resonance (NMR) analysis demonstrated interaction of aggregate matrix with the antifungal fluconazole, consistent with a role in drug impedance and contribution of multiple matrix components. 25096878 4 81 theme animal 458:463 arg1 model 465:469 a clinical niche animal model 441:469 a clinical niche animal model 441:469 In this study, we provide a comprehensive analysis of the matrix manufactured by Candida albicans both in vitro and in a clinical niche animal model. 25096878 10 82 theme proteomic 1181:1189 arg1 analysis 1191:1198 Functional matrix proteomic analysis 1163:1198 Functional matrix proteomic analysis 1163:1198 Functional matrix proteomic analysis revealed 458 distinct activities. 25096878 9 83 theme α-1,2 1036:1040 arg1 % 1068:1068 87% 1066:1068 87% 1066:1068 Newly described, more abundant polysaccharides included α-1,2 branched α-1,6-mannans (87%) associated with unbranched β-1,6-glucans (13%) in an apparent mannan-glucan complex (MGCx). 25096878 9 83 theme α-1,2 1036:1040 arg1 α-1,6-mannans 1051:1063 α-1,2 branched α-1,6-mannans 1036:1063 α-1,2 branched α-1,6-mannans (87%) associated with unbranched β-1,6-glucans (13%) in an apparent mannan-glucan complex (MGCx) 1036:1160 Newly described, more abundant polysaccharides included α-1,2 branched α-1,6-mannans (87%) associated with unbranched β-1,6-glucans (13%) in an apparent mannan-glucan complex (MGCx). 25096878 12 84 theme noncoding 1412:1420 arg1 sequences 1422:1430 noncoding sequences 1412:1430 noncoding sequences 1412:1430 Examination of matrix nucleic acid identified DNA, primarily noncoding sequences. 25096878 13 85 theme relevant 1576:1583 arg1 biofilm 1593:1599 a clinically relevant in vivo biofilm 1563:1599 a clinically relevant in vivo biofilm 1563:1599 Several of the in vitro matrix components, including proteins and each of the polysaccharides, were also present in the matrix of a clinically relevant in vivo biofilm. 25096878 10 86 theme Functional 1163:1172 arg1 analysis 1191:1198 Functional matrix proteomic analysis 1163:1198 Functional matrix proteomic analysis 1163:1198 Functional matrix proteomic analysis revealed 458 distinct activities. 25096878 8 87 theme matrix 959:964 arg1 carbohydrate 966:977 the total matrix carbohydrate 949:977 the total matrix carbohydrate 949:977 Surprisingly, a previously identified polysaccharide of functional importance, β-1,3-glucan, comprised only a small portion of the total matrix carbohydrate. 25096878 5 88 theme drug 550:553 arg1 resistance 555:564 drug resistance 550:564 drug resistance 550:564 We further explore the function of matrix components, including the impact on drug resistance. 25096878 16 89 theme unique 2146:2151 arg1 resource 2153:2160 a unique resource 2144:2160 a unique resource for further functional investigation of the biofilm matrix, a defining trait of this lifestyle 2144:2255 The availability of these biochemical analyses provides a unique resource for further functional investigation of the biofilm matrix, a defining trait of this lifestyle. 25096878 15 90 from drugs 2081:2085 arg1 protection 2054:2063 protection 2054:2063 protection from antifungal drugs 2054:2085 Importance: This report is the first to decipher the complex and unique macromolecular composition of the Candida biofilm matrix, demonstrate the clinical relevance of matrix components, and show that multiple matrix components are needed for protection from antifungal drugs. 25096878 6 91 theme % 647:647 arg1 carbohydrate 649:660 25% carbohydrate 645:660 25% carbohydrate 645:660 We uncovered components from each of the macromolecular classes (55% protein, 25% carbohydrate, 15% lipid, and 5% nucleic acid) in the C. albicans biofilm matrix. 25096878 6 91 theme % 647:647 arg1 classes 623:629 the macromolecular classes 604:629 the macromolecular classes (55% protein, 25% carbohydrate, 15% lipid, and 5% nucleic acid) 604:693 We uncovered components from each of the macromolecular classes (55% protein, 25% carbohydrate, 15% lipid, and 5% nucleic acid) in the C. albicans biofilm matrix. 25096878 10 92 theme distinct 1213:1220 arg1 activities 1222:1231 458 distinct activities 1209:1231 458 distinct activities 1209:1231 Functional matrix proteomic analysis revealed 458 distinct activities. 25096878 15 93 theme matrix 1933:1938 arg1 composition 1898:1908 the complex and unique macromolecular composition 1860:1908 the complex and unique macromolecular composition of the Candida biofilm matrix 1860:1938 Importance: This report is the first to decipher the complex and unique macromolecular composition of the Candida biofilm matrix, demonstrate the clinical relevance of matrix components, and show that multiple matrix components are needed for protection from antifungal drugs. 25096878 4 94 theme clinical 443:450 arg1 model 465:469 a clinical niche animal model 441:469 a clinical niche animal model 441:469 In this study, we provide a comprehensive analysis of the matrix manufactured by Candida albicans both in vitro and in a clinical niche animal model. 25096878 11 95 theme matrix 1238:1243 arg1 lipids 1245:1250 The matrix lipids 1234:1250 The matrix lipids 1234:1250 The matrix lipids consisted of neutral glycerolipids (89.1%), polar glycerolipids (10.4%), and sphingolipids (0.5%). 25096878 16 96 theme biochemical 2114:2124 arg1 analyses 2126:2133 these biochemical analyses 2108:2133 these biochemical analyses 2108:2133 The availability of these biochemical analyses provides a unique resource for further functional investigation of the biofilm matrix, a defining trait of this lifestyle. 25096878 15 97 theme Candida 1917:1923 arg1 matrix 1933:1938 the Candida biofilm matrix 1913:1938 the Candida biofilm matrix 1913:1938 Importance: This report is the first to decipher the complex and unique macromolecular composition of the Candida biofilm matrix, demonstrate the clinical relevance of matrix components, and show that multiple matrix components are needed for protection from antifungal drugs. 25096878 6 98 theme biofilm 714:720 arg1 matrix 722:727 the C. albicans biofilm matrix 698:727 the C. albicans biofilm matrix 698:727 We uncovered components from each of the macromolecular classes (55% protein, 25% carbohydrate, 15% lipid, and 5% nucleic acid) in the C. albicans biofilm matrix. 25096878 6 99 theme % 634:634 arg1 classes 623:629 the macromolecular classes 604:629 the macromolecular classes (55% protein, 25% carbohydrate, 15% lipid, and 5% nucleic acid) 604:693 We uncovered components from each of the macromolecular classes (55% protein, 25% carbohydrate, 15% lipid, and 5% nucleic acid) in the C. albicans biofilm matrix. 25096878 6 99 theme % 634:634 arg1 protein 636:642 55% protein 632:642 55% protein 632:642 We uncovered components from each of the macromolecular classes (55% protein, 25% carbohydrate, 15% lipid, and 5% nucleic acid) in the C. albicans biofilm matrix. 25096878 9 100 theme branched 1042:1049 arg1 % 1068:1068 87% 1066:1068 87% 1066:1068 Newly described, more abundant polysaccharides included α-1,2 branched α-1,6-mannans (87%) associated with unbranched β-1,6-glucans (13%) in an apparent mannan-glucan complex (MGCx). 25096878 9 100 theme branched 1042:1049 arg1 α-1,6-mannans 1051:1063 α-1,2 branched α-1,6-mannans 1036:1063 α-1,2 branched α-1,6-mannans (87%) associated with unbranched β-1,6-glucans (13%) in an apparent mannan-glucan complex (MGCx) 1036:1160 Newly described, more abundant polysaccharides included α-1,2 branched α-1,6-mannans (87%) associated with unbranched β-1,6-glucans (13%) in an apparent mannan-glucan complex (MGCx). 25096878 0 101 theme biofilm 26:32 arg1 encyclopedia 41:52 a fungal biofilm matrix encyclopedia 17:52 a fungal biofilm matrix encyclopedia 17:52 Novel entries in a fungal biofilm matrix encyclopedia. 25096878 14 102 theme aggregate 1672:1680 arg1 matrix 1682:1687 aggregate matrix 1672:1687 aggregate matrix 1672:1687 Nuclear magnetic resonance (NMR) analysis demonstrated interaction of aggregate matrix with the antifungal fluconazole, consistent with a role in drug impedance and contribution of multiple matrix components. 25096878 12 103 theme acid 1381:1384 arg1 Examination 1351:1361 Examination 1351:1361 Examination of matrix nucleic acid 1351:1384 Examination of matrix nucleic acid identified DNA, primarily noncoding sequences. 25096878 15 104 theme unique 1876:1881 arg1 composition 1898:1908 the complex and unique macromolecular composition 1860:1908 the complex and unique macromolecular composition of the Candida biofilm matrix 1860:1938 Importance: This report is the first to decipher the complex and unique macromolecular composition of the Candida biofilm matrix, demonstrate the clinical relevance of matrix components, and show that multiple matrix components are needed for protection from antifungal drugs. 25096878 6 105 theme 5 678:678 arg1 % 679:679 % 679:679 % 679:679 We uncovered components from each of the macromolecular classes (55% protein, 25% carbohydrate, 15% lipid, and 5% nucleic acid) in the C. albicans biofilm matrix. 25096878 15 106 theme components 1986:1995 arg1 relevance 1966:1974 the clinical relevance 1953:1974 the clinical relevance of matrix components 1953:1995 Importance: This report is the first to decipher the complex and unique macromolecular composition of the Candida biofilm matrix, demonstrate the clinical relevance of matrix components, and show that multiple matrix components are needed for protection from antifungal drugs. 25096878 15 107 theme complex 1864:1870 arg1 composition 1898:1908 the complex and unique macromolecular composition 1860:1908 the complex and unique macromolecular composition of the Candida biofilm matrix 1860:1938 Importance: This report is the first to decipher the complex and unique macromolecular composition of the Candida biofilm matrix, demonstrate the clinical relevance of matrix components, and show that multiple matrix components are needed for protection from antifungal drugs. 25096878 6 108 theme % 665:665 arg1 classes 623:629 the macromolecular classes 604:629 the macromolecular classes (55% protein, 25% carbohydrate, 15% lipid, and 5% nucleic acid) 604:693 We uncovered components from each of the macromolecular classes (55% protein, 25% carbohydrate, 15% lipid, and 5% nucleic acid) in the C. albicans biofilm matrix. 25096878 6 108 theme % 665:665 arg1 lipid 667:671 15% lipid 663:671 15% lipid 663:671 We uncovered components from each of the macromolecular classes (55% protein, 25% carbohydrate, 15% lipid, and 5% nucleic acid) in the C. albicans biofilm matrix. 25096878 12 109 theme matrix 1366:1371 arg1 acid 1381:1384 matrix nucleic acid 1366:1384 matrix nucleic acid 1366:1384 Examination of matrix nucleic acid identified DNA, primarily noncoding sequences. 25096878 15 110 theme clinical 1957:1964 arg1 relevance 1966:1974 the clinical relevance 1953:1974 the clinical relevance of matrix components 1953:1995 Importance: This report is the first to decipher the complex and unique macromolecular composition of the Candida biofilm matrix, demonstrate the clinical relevance of matrix components, and show that multiple matrix components are needed for protection from antifungal drugs. 25096878 9 111 theme unbranched 1087:1096 arg1 % 1115:1115 13% 1113:1115 13% 1113:1115 Newly described, more abundant polysaccharides included α-1,2 branched α-1,6-mannans (87%) associated with unbranched β-1,6-glucans (13%) in an apparent mannan-glucan complex (MGCx). 25096878 9 111 theme unbranched 1087:1096 arg1 β-1,6-glucans 1098:1110 unbranched β-1,6-glucans 1087:1110 unbranched β-1,6-glucans (13%) in an apparent mannan-glucan complex (MGCx) 1087:1160 Newly described, more abundant polysaccharides included α-1,2 branched α-1,6-mannans (87%) associated with unbranched β-1,6-glucans (13%) in an apparent mannan-glucan complex (MGCx). 25096878 14 112 theme resonance 1619:1627 arg1 analysis 1635:1642 Nuclear magnetic resonance (NMR) analysis 1602:1642 Nuclear magnetic resonance (NMR) analysis 1602:1642 Nuclear magnetic resonance (NMR) analysis demonstrated interaction of aggregate matrix with the antifungal fluconazole, consistent with a role in drug impedance and contribution of multiple matrix components. 25499496 8 0 theme study 1605:1609 arg1 results 1589:1595 the results 1585:1595 the results of this study 1585:1609 Overall, the results of this study demonstrated that the special designing of ITPAR maintained a sufficient number of methanogens, more diverse communities and stronger syntrophic associations among microorganisms, which made two phase anaerobic digestion of cellulosic materials more efficient. 25499496 8 1 theme sufficient 1673:1682 arg1 number 1684:1689 a sufficient number 1671:1689 a sufficient number 1671:1689 Overall, the results of this study demonstrated that the special designing of ITPAR maintained a sufficient number of methanogens, more diverse communities and stronger syntrophic associations among microorganisms, which made two phase anaerobic digestion of cellulosic materials more efficient. 25499496 1 2 theme library 250:256 arg1 technology 258:267 rDNA clone library technology 239:267 rDNA clone library technology 239:267 The microbial community structures in an integrated two-phase anaerobic reactor (ITPAR) were investigated by 16S rDNA clone library technology. 25499496 7 3 theme pH 1476:1477 arg1 values 1479:1484 pH values 1476:1484 pH values 1476:1484 The differentiation of methanogenic community composition in two phases, as well as pH values and volatile fatty acid (VFA) concentrations confirmed the phase separation of the ITPAR. 25499496 4 4 theme acidogenic 868:877 arg1 unit 879:882 the acidogenic unit 864:882 the acidogenic unit 864:882 The results showed that many kinds of cellulose and glycan decomposition bacteria related with Bacteroidales, Clostridiales and Syntrophobacterales were dominated in the reactor, with more bacteria community diversities in the acidogenic unit. 25499496 3 5 theme co-digest 505:513 arg1 wastes 531:536 co-digest fruit/vegetable wastes 505:536 co-digest fruit/vegetable wastes 505:536 The reactor had been operated for 21 stages to co-digest fruit/vegetable wastes and wheat straw, which showed a very good biogas production and decomposition of cellulosic materials. 25499496 4 6 theme more 825:828 arg1 bacteria 830:837 more bacteria 825:837 more bacteria community diversities in the acidogenic unit 825:882 The results showed that many kinds of cellulose and glycan decomposition bacteria related with Bacteroidales, Clostridiales and Syntrophobacterales were dominated in the reactor, with more bacteria community diversities in the acidogenic unit. 25499496 7 7 theme community 1428:1436 arg1 composition 1438:1448 methanogenic community composition 1415:1448 methanogenic community composition 1415:1448 The differentiation of methanogenic community composition in two phases, as well as pH values and volatile fatty acid (VFA) concentrations confirmed the phase separation of the ITPAR. 25499496 6 8 theme beta 1232:1235 arg1 indexes 1247:1253 The beta diversity indexes 1228:1253 The beta diversity indexes 1228:1253 The beta diversity indexes illustrated a more similar distribution of bacterial communities than that of methanogens between acidogenic unit and methanogenic unit. 25499496 0 9 theme Microbial 0:8 arg1 structures 20:29 Microbial community structures 0:29 Microbial community structures in an integrated two-phase anaerobic bioreactor 0:77 Microbial community structures in an integrated two-phase anaerobic bioreactor fed by fruit vegetable wastes and wheat straw. 25499496 1 10 theme two-phase 178:186 arg1 ITPAR 207:211 ITPAR 207:211 ITPAR 207:211 The microbial community structures in an integrated two-phase anaerobic reactor (ITPAR) were investigated by 16S rDNA clone library technology. 25499496 1 10 theme two-phase 178:186 arg1 reactor 198:204 an integrated two-phase anaerobic reactor 164:204 an integrated two-phase anaerobic reactor (ITPAR) 164:212 The microbial community structures in an integrated two-phase anaerobic reactor (ITPAR) were investigated by 16S rDNA clone library technology. 25499496 4 11 theme community 839:847 arg1 diversities 849:859 community diversities 839:859 more bacteria community diversities in the acidogenic unit 825:882 The results showed that many kinds of cellulose and glycan decomposition bacteria related with Bacteroidales, Clostridiales and Syntrophobacterales were dominated in the reactor, with more bacteria community diversities in the acidogenic unit. 25499496 3 12 theme wheat 542:546 arg1 straw 548:552 wheat straw 542:552 wheat straw 542:552 The reactor had been operated for 21 stages to co-digest fruit/vegetable wastes and wheat straw, which showed a very good biogas production and decomposition of cellulosic materials. 25499496 8 13 theme diverse 1712:1718 arg1 communities 1720:1730 more diverse communities 1707:1730 more diverse communities 1707:1730 Overall, the results of this study demonstrated that the special designing of ITPAR maintained a sufficient number of methanogens, more diverse communities and stronger syntrophic associations among microorganisms, which made two phase anaerobic digestion of cellulosic materials more efficient. 25499496 5 14 from methanogenesis 1187:1200 arg1 unit 1222:1225 the methanogenic unit 1205:1225 the methanogenic unit 1205:1225 The methanogens were mostly related with Methanosaeta, Methanosarcina, Methanoculleus, Methanospirillum and Methanobacterium; the predominating genus Methanosaeta, accounting for 40.5%, 54.2%, 73.6% and 78.7% in four samples from top to bottom, indicated a major methanogenesis pathway by acetoclastic methanogenesis in the methanogenic unit. 25499496 4 15 with related 723:729 arg1 Syntrophobacterales 769:787 Syntrophobacterales 769:787 Syntrophobacterales 769:787 The results showed that many kinds of cellulose and glycan decomposition bacteria related with Bacteroidales, Clostridiales and Syntrophobacterales were dominated in the reactor, with more bacteria community diversities in the acidogenic unit. 25499496 4 15 with related 723:729 arg1 Clostridiales 751:763 Clostridiales 751:763 Clostridiales 751:763 The results showed that many kinds of cellulose and glycan decomposition bacteria related with Bacteroidales, Clostridiales and Syntrophobacterales were dominated in the reactor, with more bacteria community diversities in the acidogenic unit. 25499496 6 16 theme communities 1308:1318 arg1 distribution 1282:1293 a more similar distribution 1267:1293 a more similar distribution of bacterial communities 1267:1318 The beta diversity indexes illustrated a more similar distribution of bacterial communities than that of methanogens between acidogenic unit and methanogenic unit. 25499496 8 17 theme syntrophic 1745:1754 arg1 associations 1756:1767 stronger syntrophic associations 1736:1767 stronger syntrophic associations among microorganisms 1736:1788 Overall, the results of this study demonstrated that the special designing of ITPAR maintained a sufficient number of methanogens, more diverse communities and stronger syntrophic associations among microorganisms, which made two phase anaerobic digestion of cellulosic materials more efficient. 25499496 6 18 theme similar 1274:1280 arg1 distribution 1282:1293 a more similar distribution 1267:1293 a more similar distribution of bacterial communities 1267:1318 The beta diversity indexes illustrated a more similar distribution of bacterial communities than that of methanogens between acidogenic unit and methanogenic unit. 25499496 3 19 theme biogas 580:585 arg1 production 587:596 very good biogas production 570:596 very good biogas production 570:596 The reactor had been operated for 21 stages to co-digest fruit/vegetable wastes and wheat straw, which showed a very good biogas production and decomposition of cellulosic materials. 25499496 1 20 theme microbial 130:138 arg1 structures 150:159 The microbial community structures 126:159 The microbial community structures in an integrated two-phase anaerobic reactor (ITPAR) 126:212 The microbial community structures in an integrated two-phase anaerobic reactor (ITPAR) were investigated by 16S rDNA clone library technology. 25499496 7 21 theme ITPAR 1569:1573 arg1 separation 1551:1560 the phase separation 1541:1560 the phase separation of the ITPAR 1541:1573 The differentiation of methanogenic community composition in two phases, as well as pH values and volatile fatty acid (VFA) concentrations confirmed the phase separation of the ITPAR. 25499496 0 22 from structures 20:29 arg1 bioreactor 68:77 an integrated two-phase anaerobic bioreactor 34:77 an integrated two-phase anaerobic bioreactor 34:77 Microbial community structures in an integrated two-phase anaerobic bioreactor fed by fruit vegetable wastes and wheat straw. 25499496 4 23 theme many 665:668 arg1 kinds 670:674 many kinds 665:674 many kinds of cellulose and glycan decomposition bacteria related with Bacteroidales, Clostridiales and Syntrophobacterales 665:787 The results showed that many kinds of cellulose and glycan decomposition bacteria related with Bacteroidales, Clostridiales and Syntrophobacterales were dominated in the reactor, with more bacteria community diversities in the acidogenic unit. 25499496 8 24 theme phase 1806:1810 arg1 digestion 1822:1830 two phase anaerobic digestion 1802:1830 two phase anaerobic digestion of cellulosic materials 1802:1854 Overall, the results of this study demonstrated that the special designing of ITPAR maintained a sufficient number of methanogens, more diverse communities and stronger syntrophic associations among microorganisms, which made two phase anaerobic digestion of cellulosic materials more efficient. 25499496 2 25 dep top 342:344 arg1 the 338:340 the 338:340 the 338:340 The 75L reactor was designed with a 25L rotating acidogenic unit at the top and a 50L conventional upflow methanogenic unit at the bottom, with a recirculation connected to the two units. 25499496 6 26 theme acidogenic 1353:1362 arg1 unit 1364:1367 acidogenic unit 1353:1367 acidogenic unit 1353:1367 The beta diversity indexes illustrated a more similar distribution of bacterial communities than that of methanogens between acidogenic unit and methanogenic unit. 25499496 7 27 theme phase 1545:1549 arg1 separation 1551:1560 the phase separation 1541:1560 the phase separation of the ITPAR 1541:1573 The differentiation of methanogenic community composition in two phases, as well as pH values and volatile fatty acid (VFA) concentrations confirmed the phase separation of the ITPAR. 25499496 2 28 theme methanogenic 376:387 arg1 unit 389:392 a 50L conventional upflow methanogenic unit 350:392 a 50L conventional upflow methanogenic unit 350:392 The 75L reactor was designed with a 25L rotating acidogenic unit at the top and a 50L conventional upflow methanogenic unit at the bottom, with a recirculation connected to the two units. 25499496 5 29 from % 1075:1075 arg1 top 1115:1117 top 1115:1117 top to bottom 1115:1127 The methanogens were mostly related with Methanosaeta, Methanosarcina, Methanoculleus, Methanospirillum and Methanobacterium; the predominating genus Methanosaeta, accounting for 40.5%, 54.2%, 73.6% and 78.7% in four samples from top to bottom, indicated a major methanogenesis pathway by acetoclastic methanogenesis in the methanogenic unit. 25499496 5 29 from % 1075:1075 arg1 samples 1102:1108 four samples 1097:1108 four samples from top to bottom 1097:1127 The methanogens were mostly related with Methanosaeta, Methanosarcina, Methanoculleus, Methanospirillum and Methanobacterium; the predominating genus Methanosaeta, accounting for 40.5%, 54.2%, 73.6% and 78.7% in four samples from top to bottom, indicated a major methanogenesis pathway by acetoclastic methanogenesis in the methanogenic unit. 25499496 8 30 theme cellulosic 1835:1844 arg1 materials 1846:1854 cellulosic materials 1835:1854 cellulosic materials 1835:1854 Overall, the results of this study demonstrated that the special designing of ITPAR maintained a sufficient number of methanogens, more diverse communities and stronger syntrophic associations among microorganisms, which made two phase anaerobic digestion of cellulosic materials more efficient. 25499496 4 31 theme decomposition 700:712 arg1 bacteria 714:721 cellulose and glycan decomposition bacteria 679:721 cellulose and glycan decomposition bacteria related with Bacteroidales, Clostridiales and Syntrophobacterales 679:787 The results showed that many kinds of cellulose and glycan decomposition bacteria related with Bacteroidales, Clostridiales and Syntrophobacterales were dominated in the reactor, with more bacteria community diversities in the acidogenic unit. 25499496 2 32 theme conventional 356:367 arg1 unit 389:392 a 50L conventional upflow methanogenic unit 350:392 a 50L conventional upflow methanogenic unit 350:392 The 75L reactor was designed with a 25L rotating acidogenic unit at the top and a 50L conventional upflow methanogenic unit at the bottom, with a recirculation connected to the two units. 25499496 4 33 dep bacteria 830:837 arg1 diversities 849:859 community diversities 839:859 more bacteria community diversities in the acidogenic unit 825:882 The results showed that many kinds of cellulose and glycan decomposition bacteria related with Bacteroidales, Clostridiales and Syntrophobacterales were dominated in the reactor, with more bacteria community diversities in the acidogenic unit. 25499496 4 34 theme related 723:729 arg1 bacteria 714:721 cellulose and glycan decomposition bacteria 679:721 cellulose and glycan decomposition bacteria related with Bacteroidales, Clostridiales and Syntrophobacterales 679:787 The results showed that many kinds of cellulose and glycan decomposition bacteria related with Bacteroidales, Clostridiales and Syntrophobacterales were dominated in the reactor, with more bacteria community diversities in the acidogenic unit. 25499496 5 35 theme major 1142:1146 arg1 pathway 1163:1169 a major methanogenesis pathway 1140:1169 a major methanogenesis pathway 1140:1169 The methanogens were mostly related with Methanosaeta, Methanosarcina, Methanoculleus, Methanospirillum and Methanobacterium; the predominating genus Methanosaeta, accounting for 40.5%, 54.2%, 73.6% and 78.7% in four samples from top to bottom, indicated a major methanogenesis pathway by acetoclastic methanogenesis in the methanogenic unit. 25499496 0 36 theme two-phase 48:56 arg1 bioreactor 68:77 an integrated two-phase anaerobic bioreactor 34:77 an integrated two-phase anaerobic bioreactor 34:77 Microbial community structures in an integrated two-phase anaerobic bioreactor fed by fruit vegetable wastes and wheat straw. 25499496 7 37 theme acid 1505:1508 arg1 concentrations 1516:1529 volatile fatty acid (VFA) concentrations 1490:1529 volatile fatty acid (VFA) concentrations 1490:1529 The differentiation of methanogenic community composition in two phases, as well as pH values and volatile fatty acid (VFA) concentrations confirmed the phase separation of the ITPAR. 25499496 2 38 theme acidogenic 319:328 arg1 unit 330:333 acidogenic unit 319:333 acidogenic unit 319:333 The 75L reactor was designed with a 25L rotating acidogenic unit at the top and a 50L conventional upflow methanogenic unit at the bottom, with a recirculation connected to the two units. 25499496 3 39 dep production 587:596 arg1 a 568:568 a 568:568 a 568:568 The reactor had been operated for 21 stages to co-digest fruit/vegetable wastes and wheat straw, which showed a very good biogas production and decomposition of cellulosic materials. 25499496 7 40 theme volatile 1490:1497 arg1 concentrations 1516:1529 volatile fatty acid (VFA) concentrations 1490:1529 volatile fatty acid (VFA) concentrations 1490:1529 The differentiation of methanogenic community composition in two phases, as well as pH values and volatile fatty acid (VFA) concentrations confirmed the phase separation of the ITPAR. 25499496 3 41 theme materials 630:638 arg1 decomposition 602:614 decomposition 602:614 decomposition 602:614 The reactor had been operated for 21 stages to co-digest fruit/vegetable wastes and wheat straw, which showed a very good biogas production and decomposition of cellulosic materials. 25499496 3 41 theme materials 630:638 arg1 production 587:596 very good biogas production 570:596 very good biogas production 570:596 The reactor had been operated for 21 stages to co-digest fruit/vegetable wastes and wheat straw, which showed a very good biogas production and decomposition of cellulosic materials. 25499496 5 42 theme methanogenic 1209:1220 arg1 unit 1222:1225 the methanogenic unit 1205:1225 the methanogenic unit 1205:1225 The methanogens were mostly related with Methanosaeta, Methanosarcina, Methanoculleus, Methanospirillum and Methanobacterium; the predominating genus Methanosaeta, accounting for 40.5%, 54.2%, 73.6% and 78.7% in four samples from top to bottom, indicated a major methanogenesis pathway by acetoclastic methanogenesis in the methanogenic unit. 25499496 5 43 theme predominating 1015:1027 arg1 Methanosaeta 1035:1046 the predominating genus Methanosaeta 1011:1046 the predominating genus Methanosaeta 1011:1046 The methanogens were mostly related with Methanosaeta, Methanosarcina, Methanoculleus, Methanospirillum and Methanobacterium; the predominating genus Methanosaeta, accounting for 40.5%, 54.2%, 73.6% and 78.7% in four samples from top to bottom, indicated a major methanogenesis pathway by acetoclastic methanogenesis in the methanogenic unit. 25499496 2 44 from bottom 401:406 arg1 top 342:344 top 342:344 top 342:344 The 75L reactor was designed with a 25L rotating acidogenic unit at the top and a 50L conventional upflow methanogenic unit at the bottom, with a recirculation connected to the two units. 25499496 2 44 from bottom 401:406 arg1 unit 389:392 a 50L conventional upflow methanogenic unit 350:392 a 50L conventional upflow methanogenic unit 350:392 The 75L reactor was designed with a 25L rotating acidogenic unit at the top and a 50L conventional upflow methanogenic unit at the bottom, with a recirculation connected to the two units. 25499496 6 45 theme methanogenic 1373:1384 arg1 unit 1386:1389 methanogenic unit 1373:1389 methanogenic unit 1373:1389 The beta diversity indexes illustrated a more similar distribution of bacterial communities than that of methanogens between acidogenic unit and methanogenic unit. 25499496 8 46 theme ITPAR 1654:1658 arg1 designing 1641:1649 designing 1641:1649 designing 1641:1649 Overall, the results of this study demonstrated that the special designing of ITPAR maintained a sufficient number of methanogens, more diverse communities and stronger syntrophic associations among microorganisms, which made two phase anaerobic digestion of cellulosic materials more efficient. 25499496 1 47 theme clone 244:248 arg1 technology 258:267 rDNA clone library technology 239:267 rDNA clone library technology 239:267 The microbial community structures in an integrated two-phase anaerobic reactor (ITPAR) were investigated by 16S rDNA clone library technology. 25499496 5 48 from top 1115:1117 arg1 % 1068:1068 40.5% 1064:1068 40.5% 1064:1068 The methanogens were mostly related with Methanosaeta, Methanosarcina, Methanoculleus, Methanospirillum and Methanobacterium; the predominating genus Methanosaeta, accounting for 40.5%, 54.2%, 73.6% and 78.7% in four samples from top to bottom, indicated a major methanogenesis pathway by acetoclastic methanogenesis in the methanogenic unit. 25499496 5 48 from top 1115:1117 arg1 % 1075:1075 54.2% 1071:1075 54.2% 1071:1075 The methanogens were mostly related with Methanosaeta, Methanosarcina, Methanoculleus, Methanospirillum and Methanobacterium; the predominating genus Methanosaeta, accounting for 40.5%, 54.2%, 73.6% and 78.7% in four samples from top to bottom, indicated a major methanogenesis pathway by acetoclastic methanogenesis in the methanogenic unit. 25499496 5 48 from top 1115:1117 arg1 % 1082:1082 73.6% 1078:1082 73.6% 1078:1082 The methanogens were mostly related with Methanosaeta, Methanosarcina, Methanoculleus, Methanospirillum and Methanobacterium; the predominating genus Methanosaeta, accounting for 40.5%, 54.2%, 73.6% and 78.7% in four samples from top to bottom, indicated a major methanogenesis pathway by acetoclastic methanogenesis in the methanogenic unit. 25499496 5 48 from top 1115:1117 arg1 % 1092:1092 78.7% 1088:1092 78.7% 1088:1092 The methanogens were mostly related with Methanosaeta, Methanosarcina, Methanoculleus, Methanospirillum and Methanobacterium; the predominating genus Methanosaeta, accounting for 40.5%, 54.2%, 73.6% and 78.7% in four samples from top to bottom, indicated a major methanogenesis pathway by acetoclastic methanogenesis in the methanogenic unit. 25499496 5 48 from top 1115:1117 arg1 samples 1102:1108 four samples 1097:1108 four samples from top to bottom 1097:1127 The methanogens were mostly related with Methanosaeta, Methanosarcina, Methanoculleus, Methanospirillum and Methanobacterium; the predominating genus Methanosaeta, accounting for 40.5%, 54.2%, 73.6% and 78.7% in four samples from top to bottom, indicated a major methanogenesis pathway by acetoclastic methanogenesis in the methanogenic unit. 25499496 5 49 theme acetoclastic 1174:1185 arg1 methanogenesis 1187:1200 acetoclastic methanogenesis 1174:1200 acetoclastic methanogenesis in the methanogenic unit 1174:1225 The methanogens were mostly related with Methanosaeta, Methanosarcina, Methanoculleus, Methanospirillum and Methanobacterium; the predominating genus Methanosaeta, accounting for 40.5%, 54.2%, 73.6% and 78.7% in four samples from top to bottom, indicated a major methanogenesis pathway by acetoclastic methanogenesis in the methanogenic unit. 25499496 6 50 theme diversity 1237:1245 arg1 indexes 1247:1253 The beta diversity indexes 1228:1253 The beta diversity indexes 1228:1253 The beta diversity indexes illustrated a more similar distribution of bacterial communities than that of methanogens between acidogenic unit and methanogenic unit. 25499496 2 51 theme 75L 274:276 arg1 reactor 278:284 The 75L reactor 270:284 The 75L reactor 270:284 The 75L reactor was designed with a 25L rotating acidogenic unit at the top and a 50L conventional upflow methanogenic unit at the bottom, with a recirculation connected to the two units. 25499496 1 52 theme integrated 167:176 arg1 ITPAR 207:211 ITPAR 207:211 ITPAR 207:211 The microbial community structures in an integrated two-phase anaerobic reactor (ITPAR) were investigated by 16S rDNA clone library technology. 25499496 1 52 theme integrated 167:176 arg1 reactor 198:204 an integrated two-phase anaerobic reactor 164:204 an integrated two-phase anaerobic reactor (ITPAR) 164:212 The microbial community structures in an integrated two-phase anaerobic reactor (ITPAR) were investigated by 16S rDNA clone library technology. 25499496 7 53 theme composition 1438:1448 arg1 differentiation 1396:1410 The differentiation 1392:1410 The differentiation of methanogenic community composition in two phases, as well as pH values and volatile fatty acid (VFA) concentrations 1392:1529 The differentiation of methanogenic community composition in two phases, as well as pH values and volatile fatty acid (VFA) concentrations confirmed the phase separation of the ITPAR. 25499496 8 54 theme methanogens 1694:1704 arg1 number 1684:1689 a sufficient number 1671:1689 a sufficient number 1671:1689 Overall, the results of this study demonstrated that the special designing of ITPAR maintained a sufficient number of methanogens, more diverse communities and stronger syntrophic associations among microorganisms, which made two phase anaerobic digestion of cellulosic materials more efficient. 25499496 1 55 theme anaerobic 188:196 arg1 ITPAR 207:211 ITPAR 207:211 ITPAR 207:211 The microbial community structures in an integrated two-phase anaerobic reactor (ITPAR) were investigated by 16S rDNA clone library technology. 25499496 1 55 theme anaerobic 188:196 arg1 reactor 198:204 an integrated two-phase anaerobic reactor 164:204 an integrated two-phase anaerobic reactor (ITPAR) 164:212 The microbial community structures in an integrated two-phase anaerobic reactor (ITPAR) were investigated by 16S rDNA clone library technology. 25499496 7 56 theme methanogenic 1415:1426 arg1 composition 1438:1448 methanogenic community composition 1415:1448 methanogenic community composition 1415:1448 The differentiation of methanogenic community composition in two phases, as well as pH values and volatile fatty acid (VFA) concentrations confirmed the phase separation of the ITPAR. 25499496 3 57 theme fruit/vegetable 515:529 arg1 wastes 531:536 co-digest fruit/vegetable wastes 505:536 co-digest fruit/vegetable wastes 505:536 The reactor had been operated for 21 stages to co-digest fruit/vegetable wastes and wheat straw, which showed a very good biogas production and decomposition of cellulosic materials. 25499496 8 58 theme communities 1720:1730 arg1 number 1684:1689 a sufficient number 1671:1689 a sufficient number 1671:1689 Overall, the results of this study demonstrated that the special designing of ITPAR maintained a sufficient number of methanogens, more diverse communities and stronger syntrophic associations among microorganisms, which made two phase anaerobic digestion of cellulosic materials more efficient. 25499496 6 59 theme bacterial 1298:1306 arg1 communities 1308:1318 bacterial communities 1298:1318 bacterial communities 1298:1318 The beta diversity indexes illustrated a more similar distribution of bacterial communities than that of methanogens between acidogenic unit and methanogenic unit. 25499496 8 60 theme stronger 1736:1743 arg1 associations 1756:1767 stronger syntrophic associations 1736:1767 stronger syntrophic associations among microorganisms 1736:1788 Overall, the results of this study demonstrated that the special designing of ITPAR maintained a sufficient number of methanogens, more diverse communities and stronger syntrophic associations among microorganisms, which made two phase anaerobic digestion of cellulosic materials more efficient. 25499496 3 61 theme good 575:578 arg1 production 587:596 very good biogas production 570:596 very good biogas production 570:596 The reactor had been operated for 21 stages to co-digest fruit/vegetable wastes and wheat straw, which showed a very good biogas production and decomposition of cellulosic materials. 25499496 8 62 theme associations 1756:1767 arg1 number 1684:1689 a sufficient number 1671:1689 a sufficient number 1671:1689 Overall, the results of this study demonstrated that the special designing of ITPAR maintained a sufficient number of methanogens, more diverse communities and stronger syntrophic associations among microorganisms, which made two phase anaerobic digestion of cellulosic materials more efficient. 25499496 7 63 from differentiation 1396:1410 arg1 phases 1457:1462 two phases 1453:1462 two phases 1453:1462 The differentiation of methanogenic community composition in two phases, as well as pH values and volatile fatty acid (VFA) concentrations confirmed the phase separation of the ITPAR. 25499496 7 63 from differentiation 1396:1410 arg1 values 1479:1484 pH values 1476:1484 pH values 1476:1484 The differentiation of methanogenic community composition in two phases, as well as pH values and volatile fatty acid (VFA) concentrations confirmed the phase separation of the ITPAR. 25499496 4 64 theme cellulose 679:687 arg1 bacteria 714:721 cellulose and glycan decomposition bacteria 679:721 cellulose and glycan decomposition bacteria related with Bacteroidales, Clostridiales and Syntrophobacterales 679:787 The results showed that many kinds of cellulose and glycan decomposition bacteria related with Bacteroidales, Clostridiales and Syntrophobacterales were dominated in the reactor, with more bacteria community diversities in the acidogenic unit. 25499496 5 65 from % 1068:1068 arg1 top 1115:1117 top 1115:1117 top to bottom 1115:1127 The methanogens were mostly related with Methanosaeta, Methanosarcina, Methanoculleus, Methanospirillum and Methanobacterium; the predominating genus Methanosaeta, accounting for 40.5%, 54.2%, 73.6% and 78.7% in four samples from top to bottom, indicated a major methanogenesis pathway by acetoclastic methanogenesis in the methanogenic unit. 25499496 5 65 from % 1068:1068 arg1 samples 1102:1108 four samples 1097:1108 four samples from top to bottom 1097:1127 The methanogens were mostly related with Methanosaeta, Methanosarcina, Methanoculleus, Methanospirillum and Methanobacterium; the predominating genus Methanosaeta, accounting for 40.5%, 54.2%, 73.6% and 78.7% in four samples from top to bottom, indicated a major methanogenesis pathway by acetoclastic methanogenesis in the methanogenic unit. 25499496 1 66 theme community 140:148 arg1 structures 150:159 The microbial community structures 126:159 The microbial community structures in an integrated two-phase anaerobic reactor (ITPAR) 126:212 The microbial community structures in an integrated two-phase anaerobic reactor (ITPAR) were investigated by 16S rDNA clone library technology. 25499496 0 67 theme fruit 86:90 arg1 wastes 102:107 fruit vegetable wastes 86:107 fruit vegetable wastes 86:107 Microbial community structures in an integrated two-phase anaerobic bioreactor fed by fruit vegetable wastes and wheat straw. 25499496 4 68 from diversities 849:859 arg1 unit 879:882 the acidogenic unit 864:882 the acidogenic unit 864:882 The results showed that many kinds of cellulose and glycan decomposition bacteria related with Bacteroidales, Clostridiales and Syntrophobacterales were dominated in the reactor, with more bacteria community diversities in the acidogenic unit. 25499496 0 69 theme wheat 113:117 arg1 straw 119:123 wheat straw 113:123 wheat straw 113:123 Microbial community structures in an integrated two-phase anaerobic bioreactor fed by fruit vegetable wastes and wheat straw. 25499496 1 70 from structures 150:159 arg1 ITPAR 207:211 ITPAR 207:211 ITPAR 207:211 The microbial community structures in an integrated two-phase anaerobic reactor (ITPAR) were investigated by 16S rDNA clone library technology. 25499496 1 70 from structures 150:159 arg1 reactor 198:204 an integrated two-phase anaerobic reactor 164:204 an integrated two-phase anaerobic reactor (ITPAR) 164:212 The microbial community structures in an integrated two-phase anaerobic reactor (ITPAR) were investigated by 16S rDNA clone library technology. 25499496 8 71 theme anaerobic 1812:1820 arg1 digestion 1822:1830 two phase anaerobic digestion 1802:1830 two phase anaerobic digestion of cellulosic materials 1802:1854 Overall, the results of this study demonstrated that the special designing of ITPAR maintained a sufficient number of methanogens, more diverse communities and stronger syntrophic associations among microorganisms, which made two phase anaerobic digestion of cellulosic materials more efficient. 25499496 2 72 theme upflow 369:374 arg1 unit 389:392 a 50L conventional upflow methanogenic unit 350:392 a 50L conventional upflow methanogenic unit 350:392 The 75L reactor was designed with a 25L rotating acidogenic unit at the top and a 50L conventional upflow methanogenic unit at the bottom, with a recirculation connected to the two units. 25499496 0 73 theme community 10:18 arg1 structures 20:29 Microbial community structures 0:29 Microbial community structures in an integrated two-phase anaerobic bioreactor 0:77 Microbial community structures in an integrated two-phase anaerobic bioreactor fed by fruit vegetable wastes and wheat straw. 25499496 0 74 dep fruit 86:90 arg1 vegetable 92:100 vegetable 92:100 vegetable 92:100 Microbial community structures in an integrated two-phase anaerobic bioreactor fed by fruit vegetable wastes and wheat straw. 25499496 4 75 theme glycan 693:698 arg1 decomposition 700:712 glycan decomposition 693:712 glycan decomposition 693:712 The results showed that many kinds of cellulose and glycan decomposition bacteria related with Bacteroidales, Clostridiales and Syntrophobacterales were dominated in the reactor, with more bacteria community diversities in the acidogenic unit. 25499496 2 76 theme 50L 352:354 arg1 unit 389:392 a 50L conventional upflow methanogenic unit 350:392 a 50L conventional upflow methanogenic unit 350:392 The 75L reactor was designed with a 25L rotating acidogenic unit at the top and a 50L conventional upflow methanogenic unit at the bottom, with a recirculation connected to the two units. 25499496 5 77 from % 1082:1082 arg1 top 1115:1117 top 1115:1117 top to bottom 1115:1127 The methanogens were mostly related with Methanosaeta, Methanosarcina, Methanoculleus, Methanospirillum and Methanobacterium; the predominating genus Methanosaeta, accounting for 40.5%, 54.2%, 73.6% and 78.7% in four samples from top to bottom, indicated a major methanogenesis pathway by acetoclastic methanogenesis in the methanogenic unit. 25499496 5 77 from % 1082:1082 arg1 samples 1102:1108 four samples 1097:1108 four samples from top to bottom 1097:1127 The methanogens were mostly related with Methanosaeta, Methanosarcina, Methanoculleus, Methanospirillum and Methanobacterium; the predominating genus Methanosaeta, accounting for 40.5%, 54.2%, 73.6% and 78.7% in four samples from top to bottom, indicated a major methanogenesis pathway by acetoclastic methanogenesis in the methanogenic unit. 25499496 8 78 theme materials 1846:1854 arg1 digestion 1822:1830 two phase anaerobic digestion 1802:1830 two phase anaerobic digestion of cellulosic materials 1802:1854 Overall, the results of this study demonstrated that the special designing of ITPAR maintained a sufficient number of methanogens, more diverse communities and stronger syntrophic associations among microorganisms, which made two phase anaerobic digestion of cellulosic materials more efficient. 25499496 4 79 theme bacteria 714:721 arg1 kinds 670:674 many kinds 665:674 many kinds of cellulose and glycan decomposition bacteria related with Bacteroidales, Clostridiales and Syntrophobacterales 665:787 The results showed that many kinds of cellulose and glycan decomposition bacteria related with Bacteroidales, Clostridiales and Syntrophobacterales were dominated in the reactor, with more bacteria community diversities in the acidogenic unit. 25499496 0 80 theme integrated 37:46 arg1 bioreactor 68:77 an integrated two-phase anaerobic bioreactor 34:77 an integrated two-phase anaerobic bioreactor 34:77 Microbial community structures in an integrated two-phase anaerobic bioreactor fed by fruit vegetable wastes and wheat straw. 25499496 5 81 theme methanogenesis 1148:1161 arg1 pathway 1163:1169 a major methanogenesis pathway 1140:1169 a major methanogenesis pathway 1140:1169 The methanogens were mostly related with Methanosaeta, Methanosarcina, Methanoculleus, Methanospirillum and Methanobacterium; the predominating genus Methanosaeta, accounting for 40.5%, 54.2%, 73.6% and 78.7% in four samples from top to bottom, indicated a major methanogenesis pathway by acetoclastic methanogenesis in the methanogenic unit. 25499496 5 82 theme genus 1029:1033 arg1 Methanosaeta 1035:1046 the predominating genus Methanosaeta 1011:1046 the predominating genus Methanosaeta 1011:1046 The methanogens were mostly related with Methanosaeta, Methanosarcina, Methanoculleus, Methanospirillum and Methanobacterium; the predominating genus Methanosaeta, accounting for 40.5%, 54.2%, 73.6% and 78.7% in four samples from top to bottom, indicated a major methanogenesis pathway by acetoclastic methanogenesis in the methanogenic unit. 25499496 0 83 theme anaerobic 58:66 arg1 bioreactor 68:77 an integrated two-phase anaerobic bioreactor 34:77 an integrated two-phase anaerobic bioreactor 34:77 Microbial community structures in an integrated two-phase anaerobic bioreactor fed by fruit vegetable wastes and wheat straw. 25499496 3 84 theme cellulosic 619:628 arg1 materials 630:638 cellulosic materials 619:638 cellulosic materials 619:638 The reactor had been operated for 21 stages to co-digest fruit/vegetable wastes and wheat straw, which showed a very good biogas production and decomposition of cellulosic materials. 25499496 5 85 from % 1092:1092 arg1 top 1115:1117 top 1115:1117 top to bottom 1115:1127 The methanogens were mostly related with Methanosaeta, Methanosarcina, Methanoculleus, Methanospirillum and Methanobacterium; the predominating genus Methanosaeta, accounting for 40.5%, 54.2%, 73.6% and 78.7% in four samples from top to bottom, indicated a major methanogenesis pathway by acetoclastic methanogenesis in the methanogenic unit. 25499496 5 85 from % 1092:1092 arg1 samples 1102:1108 four samples 1097:1108 four samples from top to bottom 1097:1127 The methanogens were mostly related with Methanosaeta, Methanosarcina, Methanoculleus, Methanospirillum and Methanobacterium; the predominating genus Methanosaeta, accounting for 40.5%, 54.2%, 73.6% and 78.7% in four samples from top to bottom, indicated a major methanogenesis pathway by acetoclastic methanogenesis in the methanogenic unit. 25499496 7 86 theme fatty 1499:1503 arg1 acid 1505:1508 fatty acid 1499:1508 volatile fatty acid (VFA) concentrations 1490:1529 The differentiation of methanogenic community composition in two phases, as well as pH values and volatile fatty acid (VFA) concentrations confirmed the phase separation of the ITPAR. 25499496 7 86 theme fatty 1499:1503 arg1 VFA 1511:1513 VFA 1511:1513 VFA 1511:1513 The differentiation of methanogenic community composition in two phases, as well as pH values and volatile fatty acid (VFA) concentrations confirmed the phase separation of the ITPAR. 25499496 1 87 theme rDNA 239:242 arg1 technology 258:267 rDNA clone library technology 239:267 rDNA clone library technology 239:267 The microbial community structures in an integrated two-phase anaerobic reactor (ITPAR) were investigated by 16S rDNA clone library technology. 24831810 8 0 theme N-linked 1353:1360 arg1 glycans 1362:1368 N-linked glycans 1353:1368 N-linked glycans 1353:1368 This points to rhamnose as being a component of N-linked glycans in Archaea other than Hfx. 24831810 7 1 theme archaeal 1269:1276 arg1 oligosaccharyltransferase 1278:1302 the archaeal oligosaccharyltransferase 1265:1302 the archaeal oligosaccharyltransferase 1265:1302 Moreover, a bioinformatics screen identified homologues of agl11-14 clustered in other archaeal genomes, often as part of an extended gene cluster also containing aglB, encoding the archaeal oligosaccharyltransferase. 24831810 8 2 link N-linked 1353:1360 arg1 glycans 1362:1368 N-linked glycans 1353:1368 N-linked glycans 1353:1368 This points to rhamnose as being a component of N-linked glycans in Archaea other than Hfx. 24831810 1 3 link N-linked 204:211 arg1 glycans 213:219 two distinct N-linked glycans 191:219 two distinct N-linked glycans 191:219 In the halophilic archaea Haloferax volcanii, the surface (S)-layer glycoprotein can be modified by two distinct N-linked glycans. 24831810 1 4 theme -layer 152:157 arg1 glycoprotein 159:170 the surface (S)-layer glycoprotein 137:170 the surface (S)-layer glycoprotein 137:170 In the halophilic archaea Haloferax volcanii, the surface (S)-layer glycoprotein can be modified by two distinct N-linked glycans. 24831810 4 5 theme purified 544:551 arg1 Agl11-Agl14 553:563 purified Agl11-Agl14 544:563 purified Agl11-Agl14 544:563 Accordingly, a series of in vitro assays conducted with purified Agl11-Agl14 showed these proteins to catalyze the stepwise conversion of glucose-1-phosphate to dTDP-rhamnose, the final sugar of the tetrasaccharide glycan. 24831810 2 6 theme S-layer 254:260 arg1 glycoprotein 262:273 S-layer glycoprotein Asn-498 254:281 S-layer glycoprotein Asn-498 254:281 The tetrasaccharide attached to S-layer glycoprotein Asn-498 comprises a sulfated hexose, two hexoses and a rhamnose. 24831810 7 7 theme archaeal 1174:1181 arg1 genomes 1183:1189 other archaeal genomes 1168:1189 other archaeal genomes 1168:1189 Moreover, a bioinformatics screen identified homologues of agl11-14 clustered in other archaeal genomes, often as part of an extended gene cluster also containing aglB, encoding the archaeal oligosaccharyltransferase. 24831810 2 8 theme sulfated 295:302 arg1 rhamnose 330:337 a rhamnose 328:337 a rhamnose 328:337 The tetrasaccharide attached to S-layer glycoprotein Asn-498 comprises a sulfated hexose, two hexoses and a rhamnose. 24831810 2 8 theme sulfated 295:302 arg1 hexose 304:309 a sulfated hexose 293:309 a sulfated hexose 293:309 The tetrasaccharide attached to S-layer glycoprotein Asn-498 comprises a sulfated hexose, two hexoses and a rhamnose. 24831810 2 8 theme sulfated 295:302 arg1 hexoses 316:322 two hexoses 312:322 two hexoses 312:322 The tetrasaccharide attached to S-layer glycoprotein Asn-498 comprises a sulfated hexose, two hexoses and a rhamnose. 24831810 6 9 theme nucleotide-activated 955:974 arg1 rhamnose 976:983 nucleotide-activated rhamnose 955:983 nucleotide-activated rhamnose 955:983 Archaea thus synthesize nucleotide-activated rhamnose by a pathway similar to that employed by Bacteria and distinct from that used by Eukarya and viruses. 24831810 8 10 theme glycans 1362:1368 arg1 component 1340:1348 a component 1338:1348 a component of N-linked glycans 1338:1368 This points to rhamnose as being a component of N-linked glycans in Archaea other than Hfx. 24831810 4 11 theme glycan 703:708 arg1 dTDP-rhamnose 649:661 dTDP-rhamnose 649:661 dTDP-rhamnose 649:661 Accordingly, a series of in vitro assays conducted with purified Agl11-Agl14 showed these proteins to catalyze the stepwise conversion of glucose-1-phosphate to dTDP-rhamnose, the final sugar of the tetrasaccharide glycan. 24831810 4 11 theme glycan 703:708 arg1 sugar 674:678 the final sugar 664:678 the final sugar of the tetrasaccharide glycan 664:708 Accordingly, a series of in vitro assays conducted with purified Agl11-Agl14 showed these proteins to catalyze the stepwise conversion of glucose-1-phosphate to dTDP-rhamnose, the final sugar of the tetrasaccharide glycan. 24831810 6 12 from that 1053:1056 arg1 distinct 1039:1046 distinct 1039:1046 distinct 1039:1046 Archaea thus synthesize nucleotide-activated rhamnose by a pathway similar to that employed by Bacteria and distinct from that used by Eukarya and viruses. 24831810 4 13 theme stepwise 603:610 arg1 conversion 612:621 the stepwise conversion 599:621 the stepwise conversion of glucose-1-phosphate to dTDP-rhamnose, the final sugar of the tetrasaccharide glycan 599:708 Accordingly, a series of in vitro assays conducted with purified Agl11-Agl14 showed these proteins to catalyze the stepwise conversion of glucose-1-phosphate to dTDP-rhamnose, the final sugar of the tetrasaccharide glycan. 24831810 7 14 theme other 1168:1172 arg1 genomes 1183:1189 other archaeal genomes 1168:1189 other archaeal genomes 1168:1189 Moreover, a bioinformatics screen identified homologues of agl11-14 clustered in other archaeal genomes, often as part of an extended gene cluster also containing aglB, encoding the archaeal oligosaccharyltransferase. 24831810 0 15 theme Haloferax 0:8 arg1 volcanii 10:17 Haloferax volcanii 0:17 Haloferax volcanii 0:17 Haloferax volcanii N-glycosylation: delineating the pathway of dTDP-rhamnose biosynthesis. 24831810 3 16 theme precise 432:438 arg1 roles 440:444 the precise roles 428:444 the precise roles of these proteins 428:462 While Agl11-14 have been implicated in the appearance of the terminal rhamnose subunit, the precise roles of these proteins have yet to be defined. 24831810 7 17 theme cluster 1226:1232 arg1 part 1201:1204 part 1201:1204 part of an extended gene cluster also containing aglB, encoding the archaeal oligosaccharyltransferase 1201:1302 Moreover, a bioinformatics screen identified homologues of agl11-14 clustered in other archaeal genomes, often as part of an extended gene cluster also containing aglB, encoding the archaeal oligosaccharyltransferase. 24831810 7 18 theme agl11-14 1146:1153 arg1 homologues 1132:1141 homologues 1132:1141 homologues of agl11-14 clustered in other archaeal genomes, often 1132:1196 Moreover, a bioinformatics screen identified homologues of agl11-14 clustered in other archaeal genomes, often as part of an extended gene cluster also containing aglB, encoding the archaeal oligosaccharyltransferase. 24831810 5 19 theme glucose-1-phosphate 736:754 arg1 thymidylyltransferase 756:776 a glucose-1-phosphate thymidylyltransferase 734:776 a glucose-1-phosphate thymidylyltransferase 734:776 Specifically, Agl11 is a glucose-1-phosphate thymidylyltransferase, Agl12 is a dTDP-glucose-4,6-dehydratase and Agl13 is a dTDP-4-dehydro-6-deoxy-glucose-3,5-epimerase, while Agl14 is a dTDP-4-dehydrorhamnose reductase. 24831810 5 19 theme glucose-1-phosphate 736:754 arg1 Agl11 725:729 Agl11 725:729 Agl11 725:729 Specifically, Agl11 is a glucose-1-phosphate thymidylyltransferase, Agl12 is a dTDP-glucose-4,6-dehydratase and Agl13 is a dTDP-4-dehydro-6-deoxy-glucose-3,5-epimerase, while Agl14 is a dTDP-4-dehydrorhamnose reductase. 24831810 3 20 theme subunit 419:425 arg1 appearance 383:392 the appearance 379:392 the appearance of the terminal rhamnose subunit 379:425 While Agl11-14 have been implicated in the appearance of the terminal rhamnose subunit, the precise roles of these proteins have yet to be defined. 24831810 2 21 gly glycoprotein 262:273 arg1 glycoprotein 262:273 S-layer glycoprotein Asn-498 254:281 S-layer glycoprotein Asn-498 254:281 The tetrasaccharide attached to S-layer glycoprotein Asn-498 comprises a sulfated hexose, two hexoses and a rhamnose. 24831810 4 22 theme assays 522:527 arg1 series 503:508 a series 501:508 a series of in vitro assays conducted with purified Agl11-Agl14 501:563 Accordingly, a series of in vitro assays conducted with purified Agl11-Agl14 showed these proteins to catalyze the stepwise conversion of glucose-1-phosphate to dTDP-rhamnose, the final sugar of the tetrasaccharide glycan. 24831810 1 23 theme halophilic 98:107 arg1 volcanii 127:134 the halophilic archaea Haloferax volcanii 94:134 the halophilic archaea Haloferax volcanii 94:134 In the halophilic archaea Haloferax volcanii, the surface (S)-layer glycoprotein can be modified by two distinct N-linked glycans. 24831810 1 24 gly glycoprotein 159:170 arg1 glycoprotein 159:170 the surface (S)-layer glycoprotein 137:170 the surface (S)-layer glycoprotein 137:170 In the halophilic archaea Haloferax volcanii, the surface (S)-layer glycoprotein can be modified by two distinct N-linked glycans. 24831810 7 25 theme extended 1212:1219 arg1 cluster 1226:1232 an extended gene cluster 1209:1232 an extended gene cluster also containing aglB, encoding the archaeal oligosaccharyltransferase 1209:1302 Moreover, a bioinformatics screen identified homologues of agl11-14 clustered in other archaeal genomes, often as part of an extended gene cluster also containing aglB, encoding the archaeal oligosaccharyltransferase. 24831810 1 26 theme archaea 109:115 arg1 volcanii 127:134 the halophilic archaea Haloferax volcanii 94:134 the halophilic archaea Haloferax volcanii 94:134 In the halophilic archaea Haloferax volcanii, the surface (S)-layer glycoprotein can be modified by two distinct N-linked glycans. 24831810 7 27 theme gene 1221:1224 arg1 cluster 1226:1232 an extended gene cluster 1209:1232 an extended gene cluster also containing aglB, encoding the archaeal oligosaccharyltransferase 1209:1302 Moreover, a bioinformatics screen identified homologues of agl11-14 clustered in other archaeal genomes, often as part of an extended gene cluster also containing aglB, encoding the archaeal oligosaccharyltransferase. 24831810 1 28 theme Haloferax 117:125 arg1 volcanii 127:134 the halophilic archaea Haloferax volcanii 94:134 the halophilic archaea Haloferax volcanii 94:134 In the halophilic archaea Haloferax volcanii, the surface (S)-layer glycoprotein can be modified by two distinct N-linked glycans. 24831810 3 29 theme proteins 455:462 arg1 roles 440:444 the precise roles 428:444 the precise roles of these proteins 428:462 While Agl11-14 have been implicated in the appearance of the terminal rhamnose subunit, the precise roles of these proteins have yet to be defined. 24831810 3 30 theme terminal 401:408 arg1 subunit 419:425 the terminal rhamnose subunit 397:425 the terminal rhamnose subunit 397:425 While Agl11-14 have been implicated in the appearance of the terminal rhamnose subunit, the precise roles of these proteins have yet to be defined. 24831810 4 31 theme glucose-1-phosphate 626:644 arg1 conversion 612:621 the stepwise conversion 599:621 the stepwise conversion of glucose-1-phosphate to dTDP-rhamnose, the final sugar of the tetrasaccharide glycan 599:708 Accordingly, a series of in vitro assays conducted with purified Agl11-Agl14 showed these proteins to catalyze the stepwise conversion of glucose-1-phosphate to dTDP-rhamnose, the final sugar of the tetrasaccharide glycan. 24831810 1 32 theme distinct 195:202 arg1 glycans 213:219 two distinct N-linked glycans 191:219 two distinct N-linked glycans 191:219 In the halophilic archaea Haloferax volcanii, the surface (S)-layer glycoprotein can be modified by two distinct N-linked glycans. 24831810 3 33 theme rhamnose 410:417 arg1 subunit 419:425 the terminal rhamnose subunit 397:425 the terminal rhamnose subunit 397:425 While Agl11-14 have been implicated in the appearance of the terminal rhamnose subunit, the precise roles of these proteins have yet to be defined. 24831810 1 34 theme N-linked 204:211 arg1 glycans 213:219 two distinct N-linked glycans 191:219 two distinct N-linked glycans 191:219 In the halophilic archaea Haloferax volcanii, the surface (S)-layer glycoprotein can be modified by two distinct N-linked glycans. 24831810 8 35 dep other 1381:1385 arg1 than 1387:1390 than 1387:1390 than 1387:1390 This points to rhamnose as being a component of N-linked glycans in Archaea other than Hfx. 24831810 7 36 contain containing 1239:1248 arg1 cluster 1226:1232 an extended gene cluster 1209:1232 an extended gene cluster also containing aglB, encoding the archaeal oligosaccharyltransferase 1209:1302 Moreover, a bioinformatics screen identified homologues of agl11-14 clustered in other archaeal genomes, often as part of an extended gene cluster also containing aglB, encoding the archaeal oligosaccharyltransferase. 24831810 7 36 contain containing 1239:1248 arg2 aglB 1250:1253 aglB 1250:1253 aglB 1250:1253 Moreover, a bioinformatics screen identified homologues of agl11-14 clustered in other archaeal genomes, often as part of an extended gene cluster also containing aglB, encoding the archaeal oligosaccharyltransferase. 24831810 1 37 mod modified 179:186 arg3 glycans 213:219 two distinct N-linked glycans 191:219 two distinct N-linked glycans 191:219 In the halophilic archaea Haloferax volcanii, the surface (S)-layer glycoprotein can be modified by two distinct N-linked glycans. 24831810 1 37 mod modified 179:186 arg1 glycoprotein 159:170 the surface (S)-layer glycoprotein 137:170 the surface (S)-layer glycoprotein 137:170 In the halophilic archaea Haloferax volcanii, the surface (S)-layer glycoprotein can be modified by two distinct N-linked glycans. 24831810 4 38 theme in 513:514 arg1 assays 522:527 in vitro assays 513:527 in vitro assays conducted with purified Agl11-Agl14 513:563 Accordingly, a series of in vitro assays conducted with purified Agl11-Agl14 showed these proteins to catalyze the stepwise conversion of glucose-1-phosphate to dTDP-rhamnose, the final sugar of the tetrasaccharide glycan. 24831810 7 39 theme bioinformatics 1099:1112 arg1 screen 1114:1119 a bioinformatics screen 1097:1119 a bioinformatics screen 1097:1119 Moreover, a bioinformatics screen identified homologues of agl11-14 clustered in other archaeal genomes, often as part of an extended gene cluster also containing aglB, encoding the archaeal oligosaccharyltransferase. 24831810 4 40 theme tetrasaccharide 687:701 arg1 glycan 703:708 the tetrasaccharide glycan 683:708 the tetrasaccharide glycan 683:708 Accordingly, a series of in vitro assays conducted with purified Agl11-Agl14 showed these proteins to catalyze the stepwise conversion of glucose-1-phosphate to dTDP-rhamnose, the final sugar of the tetrasaccharide glycan. 24831810 6 41 theme similar 998:1004 arg1 pathway 990:996 a pathway 988:996 a pathway similar to that employed by Bacteria and distinct from that used by Eukarya and viruses 988:1084 Archaea thus synthesize nucleotide-activated rhamnose by a pathway similar to that employed by Bacteria and distinct from that used by Eukarya and viruses. 24831810 4 42 theme final 668:672 arg1 dTDP-rhamnose 649:661 dTDP-rhamnose 649:661 dTDP-rhamnose 649:661 Accordingly, a series of in vitro assays conducted with purified Agl11-Agl14 showed these proteins to catalyze the stepwise conversion of glucose-1-phosphate to dTDP-rhamnose, the final sugar of the tetrasaccharide glycan. 24831810 4 42 theme final 668:672 arg1 sugar 674:678 the final sugar 664:678 the final sugar of the tetrasaccharide glycan 664:708 Accordingly, a series of in vitro assays conducted with purified Agl11-Agl14 showed these proteins to catalyze the stepwise conversion of glucose-1-phosphate to dTDP-rhamnose, the final sugar of the tetrasaccharide glycan. 24831810 0 43 dep N-glycosylation 19:33 arg1 volcanii 10:17 Haloferax volcanii 0:17 Haloferax volcanii 0:17 Haloferax volcanii N-glycosylation: delineating the pathway of dTDP-rhamnose biosynthesis. 24831810 8 44 from component 1340:1348 arg1 Archaea 1373:1379 Archaea 1373:1379 Archaea other than Hfx 1373:1394 This points to rhamnose as being a component of N-linked glycans in Archaea other than Hfx. 24831810 8 44 from component 1340:1348 arg1 Hfx 1392:1394 Hfx 1392:1394 Archaea other than Hfx 1373:1394 This points to rhamnose as being a component of N-linked glycans in Archaea other than Hfx. 24831810 1 45 theme surface 141:147 arg1 glycoprotein 159:170 the surface (S)-layer glycoprotein 137:170 the surface (S)-layer glycoprotein 137:170 In the halophilic archaea Haloferax volcanii, the surface (S)-layer glycoprotein can be modified by two distinct N-linked glycans. 24831810 0 46 theme biosynthesis 77:88 arg1 pathway 52:58 the pathway 48:58 the pathway of dTDP-rhamnose biosynthesis 48:88 Haloferax volcanii N-glycosylation: delineating the pathway of dTDP-rhamnose biosynthesis. 24831810 5 47 theme dTDP-4-dehydrorhamnose 897:918 arg1 Agl14 886:890 Agl14 886:890 Agl14 886:890 Specifically, Agl11 is a glucose-1-phosphate thymidylyltransferase, Agl12 is a dTDP-glucose-4,6-dehydratase and Agl13 is a dTDP-4-dehydro-6-deoxy-glucose-3,5-epimerase, while Agl14 is a dTDP-4-dehydrorhamnose reductase. 24831810 5 47 theme dTDP-4-dehydrorhamnose 897:918 arg1 reductase 920:928 a dTDP-4-dehydrorhamnose reductase 895:928 a dTDP-4-dehydrorhamnose reductase 895:928 Specifically, Agl11 is a glucose-1-phosphate thymidylyltransferase, Agl12 is a dTDP-glucose-4,6-dehydratase and Agl13 is a dTDP-4-dehydro-6-deoxy-glucose-3,5-epimerase, while Agl14 is a dTDP-4-dehydrorhamnose reductase. 24831810 2 48 attach attached 242:249 arg2 tetrasaccharide 226:240 The tetrasaccharide 222:240 The tetrasaccharide attached to S-layer glycoprotein Asn-498 222:281 The tetrasaccharide attached to S-layer glycoprotein Asn-498 comprises a sulfated hexose, two hexoses and a rhamnose. 24831810 2 48 attach attached 242:249 arg1 glycoprotein 262:273 S-layer glycoprotein Asn-498 254:281 S-layer glycoprotein Asn-498 254:281 The tetrasaccharide attached to S-layer glycoprotein Asn-498 comprises a sulfated hexose, two hexoses and a rhamnose. 24831810 0 49 theme dTDP-rhamnose 63:75 arg1 biosynthesis 77:88 dTDP-rhamnose biosynthesis 63:88 dTDP-rhamnose biosynthesis 63:88 Haloferax volcanii N-glycosylation: delineating the pathway of dTDP-rhamnose biosynthesis. 24831810 4 50 dep in 513:514 arg1 vitro 516:520 vitro 516:520 vitro 516:520 Accordingly, a series of in vitro assays conducted with purified Agl11-Agl14 showed these proteins to catalyze the stepwise conversion of glucose-1-phosphate to dTDP-rhamnose, the final sugar of the tetrasaccharide glycan. 24831810 6 51 theme distinct 1039:1046 arg1 pathway 990:996 a pathway 988:996 a pathway similar to that employed by Bacteria and distinct from that used by Eukarya and viruses 988:1084 Archaea thus synthesize nucleotide-activated rhamnose by a pathway similar to that employed by Bacteria and distinct from that used by Eukarya and viruses. 24831810 1 52 theme S 150:150 arg1 glycoprotein 159:170 the surface (S)-layer glycoprotein 137:170 the surface (S)-layer glycoprotein 137:170 In the halophilic archaea Haloferax volcanii, the surface (S)-layer glycoprotein can be modified by two distinct N-linked glycans. 27618188 1 0 theme cell 346:349 arg1 factor-1 351:358 regulator host cell factor-1 331:358 the cell cycle regulator host cell factor-1 (HCF-1) 316:366 The essential human enzyme O-linked β-N-acetylglucosamine transferase (OGT), known for modulating the functions of nuclear and cytoplasmic proteins through serine and threonine glycosylation, was unexpectedly implicated in the proteolytic maturation of the cell cycle regulator host cell factor-1 (HCF-1). 27618188 1 0 theme cell 346:349 arg1 HCF-1 361:365 HCF-1 361:365 HCF-1 361:365 The essential human enzyme O-linked β-N-acetylglucosamine transferase (OGT), known for modulating the functions of nuclear and cytoplasmic proteins through serine and threonine glycosylation, was unexpectedly implicated in the proteolytic maturation of the cell cycle regulator host cell factor-1 (HCF-1). 27618188 1 1 link O-linked 90:97 arg1 OGT 134:136 OGT 134:136 OGT 134:136 The essential human enzyme O-linked β-N-acetylglucosamine transferase (OGT), known for modulating the functions of nuclear and cytoplasmic proteins through serine and threonine glycosylation, was unexpectedly implicated in the proteolytic maturation of the cell cycle regulator host cell factor-1 (HCF-1). 27618188 1 1 link O-linked 90:97 arg1 transferase 121:131 The essential human enzyme O-linked β-N-acetylglucosamine transferase 63:131 The essential human enzyme O-linked β-N-acetylglucosamine transferase (OGT) 63:137 The essential human enzyme O-linked β-N-acetylglucosamine transferase (OGT), known for modulating the functions of nuclear and cytoplasmic proteins through serine and threonine glycosylation, was unexpectedly implicated in the proteolytic maturation of the cell cycle regulator host cell factor-1 (HCF-1). 27618188 2 2 gly glycosylation 413:425 arg1 chain 447:451 a glutamate side chain 430:451 a glutamate side chain followed by on-enzyme formation of an internal pyroglutamate, which undergoes spontaneous backbone hydrolysis 430:561 Here we show that HCF-1 cleavage occurs via glycosylation of a glutamate side chain followed by on-enzyme formation of an internal pyroglutamate, which undergoes spontaneous backbone hydrolysis. 27618188 1 3 dep cycle 325:329 arg1 factor-1 351:358 regulator host cell factor-1 331:358 the cell cycle regulator host cell factor-1 (HCF-1) 316:366 The essential human enzyme O-linked β-N-acetylglucosamine transferase (OGT), known for modulating the functions of nuclear and cytoplasmic proteins through serine and threonine glycosylation, was unexpectedly implicated in the proteolytic maturation of the cell cycle regulator host cell factor-1 (HCF-1). 27618188 1 3 dep cycle 325:329 arg1 HCF-1 361:365 HCF-1 361:365 HCF-1 361:365 The essential human enzyme O-linked β-N-acetylglucosamine transferase (OGT), known for modulating the functions of nuclear and cytoplasmic proteins through serine and threonine glycosylation, was unexpectedly implicated in the proteolytic maturation of the cell cycle regulator host cell factor-1 (HCF-1). 27618188 1 4 theme essential 67:75 arg1 OGT 134:136 OGT 134:136 OGT 134:136 The essential human enzyme O-linked β-N-acetylglucosamine transferase (OGT), known for modulating the functions of nuclear and cytoplasmic proteins through serine and threonine glycosylation, was unexpectedly implicated in the proteolytic maturation of the cell cycle regulator host cell factor-1 (HCF-1). 27618188 1 4 theme essential 67:75 arg1 transferase 121:131 The essential human enzyme O-linked β-N-acetylglucosamine transferase 63:131 The essential human enzyme O-linked β-N-acetylglucosamine transferase (OGT) 63:137 The essential human enzyme O-linked β-N-acetylglucosamine transferase (OGT), known for modulating the functions of nuclear and cytoplasmic proteins through serine and threonine glycosylation, was unexpectedly implicated in the proteolytic maturation of the cell cycle regulator host cell factor-1 (HCF-1). 27618188 2 5 theme HCF-1 387:391 arg1 cleavage 393:400 HCF-1 cleavage 387:400 HCF-1 cleavage 387:400 Here we show that HCF-1 cleavage occurs via glycosylation of a glutamate side chain followed by on-enzyme formation of an internal pyroglutamate, which undergoes spontaneous backbone hydrolysis. 27618188 2 6 theme chain 447:451 arg1 glycosylation 413:425 glycosylation 413:425 glycosylation of a glutamate side chain followed by on-enzyme formation of an internal pyroglutamate, which undergoes spontaneous backbone hydrolysis 413:561 Here we show that HCF-1 cleavage occurs via glycosylation of a glutamate side chain followed by on-enzyme formation of an internal pyroglutamate, which undergoes spontaneous backbone hydrolysis. 27618188 2 7 theme on-enzyme 465:473 arg1 formation 475:483 on-enzyme formation 465:483 on-enzyme formation 465:483 Here we show that HCF-1 cleavage occurs via glycosylation of a glutamate side chain followed by on-enzyme formation of an internal pyroglutamate, which undergoes spontaneous backbone hydrolysis. 27618188 1 8 theme human 77:81 arg1 OGT 134:136 OGT 134:136 OGT 134:136 The essential human enzyme O-linked β-N-acetylglucosamine transferase (OGT), known for modulating the functions of nuclear and cytoplasmic proteins through serine and threonine glycosylation, was unexpectedly implicated in the proteolytic maturation of the cell cycle regulator host cell factor-1 (HCF-1). 27618188 1 8 theme human 77:81 arg1 transferase 121:131 The essential human enzyme O-linked β-N-acetylglucosamine transferase 63:131 The essential human enzyme O-linked β-N-acetylglucosamine transferase (OGT) 63:137 The essential human enzyme O-linked β-N-acetylglucosamine transferase (OGT), known for modulating the functions of nuclear and cytoplasmic proteins through serine and threonine glycosylation, was unexpectedly implicated in the proteolytic maturation of the cell cycle regulator host cell factor-1 (HCF-1). 27618188 2 9 theme side 442:445 arg1 chain 447:451 a glutamate side chain 430:451 a glutamate side chain followed by on-enzyme formation of an internal pyroglutamate, which undergoes spontaneous backbone hydrolysis 430:561 Here we show that HCF-1 cleavage occurs via glycosylation of a glutamate side chain followed by on-enzyme formation of an internal pyroglutamate, which undergoes spontaneous backbone hydrolysis. 27618188 1 10 theme enzyme 83:88 arg1 OGT 134:136 OGT 134:136 OGT 134:136 The essential human enzyme O-linked β-N-acetylglucosamine transferase (OGT), known for modulating the functions of nuclear and cytoplasmic proteins through serine and threonine glycosylation, was unexpectedly implicated in the proteolytic maturation of the cell cycle regulator host cell factor-1 (HCF-1). 27618188 1 10 theme enzyme 83:88 arg1 transferase 121:131 The essential human enzyme O-linked β-N-acetylglucosamine transferase 63:131 The essential human enzyme O-linked β-N-acetylglucosamine transferase (OGT) 63:137 The essential human enzyme O-linked β-N-acetylglucosamine transferase (OGT), known for modulating the functions of nuclear and cytoplasmic proteins through serine and threonine glycosylation, was unexpectedly implicated in the proteolytic maturation of the cell cycle regulator host cell factor-1 (HCF-1). 27618188 1 11 theme nuclear 178:184 arg1 proteins 202:209 nuclear and cytoplasmic proteins 178:209 nuclear and cytoplasmic proteins 178:209 The essential human enzyme O-linked β-N-acetylglucosamine transferase (OGT), known for modulating the functions of nuclear and cytoplasmic proteins through serine and threonine glycosylation, was unexpectedly implicated in the proteolytic maturation of the cell cycle regulator host cell factor-1 (HCF-1). 27618188 2 12 theme glutamate 432:440 arg1 chain 447:451 a glutamate side chain 430:451 a glutamate side chain followed by on-enzyme formation of an internal pyroglutamate, which undergoes spontaneous backbone hydrolysis 430:561 Here we show that HCF-1 cleavage occurs via glycosylation of a glutamate side chain followed by on-enzyme formation of an internal pyroglutamate, which undergoes spontaneous backbone hydrolysis. 27618188 1 13 theme O-linked 90:97 arg1 OGT 134:136 OGT 134:136 OGT 134:136 The essential human enzyme O-linked β-N-acetylglucosamine transferase (OGT), known for modulating the functions of nuclear and cytoplasmic proteins through serine and threonine glycosylation, was unexpectedly implicated in the proteolytic maturation of the cell cycle regulator host cell factor-1 (HCF-1). 27618188 1 13 theme O-linked 90:97 arg1 transferase 121:131 The essential human enzyme O-linked β-N-acetylglucosamine transferase 63:131 The essential human enzyme O-linked β-N-acetylglucosamine transferase (OGT) 63:137 The essential human enzyme O-linked β-N-acetylglucosamine transferase (OGT), known for modulating the functions of nuclear and cytoplasmic proteins through serine and threonine glycosylation, was unexpectedly implicated in the proteolytic maturation of the cell cycle regulator host cell factor-1 (HCF-1). 27618188 1 14 theme proteolytic 290:300 arg1 maturation 302:311 the proteolytic maturation 286:311 the proteolytic maturation of the cell cycle regulator host cell factor-1 (HCF-1) 286:366 The essential human enzyme O-linked β-N-acetylglucosamine transferase (OGT), known for modulating the functions of nuclear and cytoplasmic proteins through serine and threonine glycosylation, was unexpectedly implicated in the proteolytic maturation of the cell cycle regulator host cell factor-1 (HCF-1). 27618188 1 15 theme β-N-acetylglucosamine 99:119 arg1 OGT 134:136 OGT 134:136 OGT 134:136 The essential human enzyme O-linked β-N-acetylglucosamine transferase (OGT), known for modulating the functions of nuclear and cytoplasmic proteins through serine and threonine glycosylation, was unexpectedly implicated in the proteolytic maturation of the cell cycle regulator host cell factor-1 (HCF-1). 27618188 1 15 theme β-N-acetylglucosamine 99:119 arg1 transferase 121:131 The essential human enzyme O-linked β-N-acetylglucosamine transferase 63:131 The essential human enzyme O-linked β-N-acetylglucosamine transferase (OGT) 63:137 The essential human enzyme O-linked β-N-acetylglucosamine transferase (OGT), known for modulating the functions of nuclear and cytoplasmic proteins through serine and threonine glycosylation, was unexpectedly implicated in the proteolytic maturation of the cell cycle regulator host cell factor-1 (HCF-1). 27618188 1 16 theme cytoplasmic 190:200 arg1 proteins 202:209 nuclear and cytoplasmic proteins 178:209 nuclear and cytoplasmic proteins 178:209 The essential human enzyme O-linked β-N-acetylglucosamine transferase (OGT), known for modulating the functions of nuclear and cytoplasmic proteins through serine and threonine glycosylation, was unexpectedly implicated in the proteolytic maturation of the cell cycle regulator host cell factor-1 (HCF-1). 27618188 0 17 theme glycosyltransferase 8:26 arg1 OGT 28:30 the glycosyltransferase OGT 4:30 the glycosyltransferase OGT 4:30 How the glycosyltransferase OGT catalyzes amide bond cleavage. 27618188 1 18 theme proteins 202:209 arg1 functions 165:173 the functions 161:173 the functions of nuclear and cytoplasmic proteins 161:209 The essential human enzyme O-linked β-N-acetylglucosamine transferase (OGT), known for modulating the functions of nuclear and cytoplasmic proteins through serine and threonine glycosylation, was unexpectedly implicated in the proteolytic maturation of the cell cycle regulator host cell factor-1 (HCF-1). 27618188 0 19 theme amide 42:46 arg1 cleavage 53:60 amide bond cleavage 42:60 amide bond cleavage 42:60 How the glycosyltransferase OGT catalyzes amide bond cleavage. 27618188 2 20 theme backbone 543:550 arg1 hydrolysis 552:561 spontaneous backbone hydrolysis 531:561 spontaneous backbone hydrolysis 531:561 Here we show that HCF-1 cleavage occurs via glycosylation of a glutamate side chain followed by on-enzyme formation of an internal pyroglutamate, which undergoes spontaneous backbone hydrolysis. 27618188 2 21 theme spontaneous 531:541 arg1 hydrolysis 552:561 spontaneous backbone hydrolysis 531:561 spontaneous backbone hydrolysis 531:561 Here we show that HCF-1 cleavage occurs via glycosylation of a glutamate side chain followed by on-enzyme formation of an internal pyroglutamate, which undergoes spontaneous backbone hydrolysis. 27618188 2 22 theme pyroglutamate 500:512 arg1 formation 475:483 on-enzyme formation 465:483 on-enzyme formation 465:483 Here we show that HCF-1 cleavage occurs via glycosylation of a glutamate side chain followed by on-enzyme formation of an internal pyroglutamate, which undergoes spontaneous backbone hydrolysis. 27618188 1 23 theme cell 320:323 arg1 cycle 325:329 the cell cycle regulator host cell factor-1 (HCF-1) 316:366 the cell cycle regulator host cell factor-1 (HCF-1) 316:366 The essential human enzyme O-linked β-N-acetylglucosamine transferase (OGT), known for modulating the functions of nuclear and cytoplasmic proteins through serine and threonine glycosylation, was unexpectedly implicated in the proteolytic maturation of the cell cycle regulator host cell factor-1 (HCF-1). 27618188 0 24 theme bond 48:51 arg1 cleavage 53:60 amide bond cleavage 42:60 amide bond cleavage 42:60 How the glycosyltransferase OGT catalyzes amide bond cleavage. 27618188 1 25 theme cycle 325:329 arg1 maturation 302:311 the proteolytic maturation 286:311 the proteolytic maturation of the cell cycle regulator host cell factor-1 (HCF-1) 286:366 The essential human enzyme O-linked β-N-acetylglucosamine transferase (OGT), known for modulating the functions of nuclear and cytoplasmic proteins through serine and threonine glycosylation, was unexpectedly implicated in the proteolytic maturation of the cell cycle regulator host cell factor-1 (HCF-1). 27618188 1 26 theme regulator 331:339 arg1 factor-1 351:358 regulator host cell factor-1 331:358 the cell cycle regulator host cell factor-1 (HCF-1) 316:366 The essential human enzyme O-linked β-N-acetylglucosamine transferase (OGT), known for modulating the functions of nuclear and cytoplasmic proteins through serine and threonine glycosylation, was unexpectedly implicated in the proteolytic maturation of the cell cycle regulator host cell factor-1 (HCF-1). 27618188 1 26 theme regulator 331:339 arg1 HCF-1 361:365 HCF-1 361:365 HCF-1 361:365 The essential human enzyme O-linked β-N-acetylglucosamine transferase (OGT), known for modulating the functions of nuclear and cytoplasmic proteins through serine and threonine glycosylation, was unexpectedly implicated in the proteolytic maturation of the cell cycle regulator host cell factor-1 (HCF-1). 27618188 1 27 dep serine 219:224 arg1 glycosylation 240:252 glycosylation 240:252 glycosylation 240:252 The essential human enzyme O-linked β-N-acetylglucosamine transferase (OGT), known for modulating the functions of nuclear and cytoplasmic proteins through serine and threonine glycosylation, was unexpectedly implicated in the proteolytic maturation of the cell cycle regulator host cell factor-1 (HCF-1). 27618188 1 28 theme host 341:344 arg1 factor-1 351:358 regulator host cell factor-1 331:358 the cell cycle regulator host cell factor-1 (HCF-1) 316:366 The essential human enzyme O-linked β-N-acetylglucosamine transferase (OGT), known for modulating the functions of nuclear and cytoplasmic proteins through serine and threonine glycosylation, was unexpectedly implicated in the proteolytic maturation of the cell cycle regulator host cell factor-1 (HCF-1). 27618188 1 28 theme host 341:344 arg1 HCF-1 361:365 HCF-1 361:365 HCF-1 361:365 The essential human enzyme O-linked β-N-acetylglucosamine transferase (OGT), known for modulating the functions of nuclear and cytoplasmic proteins through serine and threonine glycosylation, was unexpectedly implicated in the proteolytic maturation of the cell cycle regulator host cell factor-1 (HCF-1). 27332727 1 0 theme remarkable 150:159 arg1 success 161:167 remarkable success 150:167 remarkable success in eradicating hematological malignancies 150:209 Engineering T cells with chimeric antigen receptors (CARs) has demonstrated remarkable success in eradicating hematological malignancies. 27332727 2 1 link O-linked 338:345 arg1 Tn 373:374 Tn 373:374 Tn 373:374 In this issue of Immunity, June and colleagues demonstrate the broad antitumor efficacy of a newly-designed CAR targeting the O-linked hypoglycosylated epitopes Tn and sialyl-Tn on cancer-associated MUC-1. 27332727 2 1 link O-linked 338:345 arg1 epitopes 364:371 the O-linked hypoglycosylated epitopes Tn and sialyl-Tn 334:388 the O-linked hypoglycosylated epitopes Tn and sialyl-Tn on cancer-associated MUC-1 334:415 In this issue of Immunity, June and colleagues demonstrate the broad antitumor efficacy of a newly-designed CAR targeting the O-linked hypoglycosylated epitopes Tn and sialyl-Tn on cancer-associated MUC-1. 27332727 2 1 link O-linked 338:345 arg1 sialyl-Tn 380:388 sialyl-Tn 380:388 sialyl-Tn 380:388 In this issue of Immunity, June and colleagues demonstrate the broad antitumor efficacy of a newly-designed CAR targeting the O-linked hypoglycosylated epitopes Tn and sialyl-Tn on cancer-associated MUC-1. 27332727 2 2 theme CAR 320:322 arg1 efficacy 291:298 the broad antitumor efficacy 271:298 the broad antitumor efficacy of a newly-designed CAR targeting the O-linked hypoglycosylated epitopes Tn and sialyl-Tn on cancer-associated MUC-1 271:415 In this issue of Immunity, June and colleagues demonstrate the broad antitumor efficacy of a newly-designed CAR targeting the O-linked hypoglycosylated epitopes Tn and sialyl-Tn on cancer-associated MUC-1. 27332727 2 3 dep epitopes 364:371 arg1 Tn 373:374 Tn 373:374 Tn 373:374 In this issue of Immunity, June and colleagues demonstrate the broad antitumor efficacy of a newly-designed CAR targeting the O-linked hypoglycosylated epitopes Tn and sialyl-Tn on cancer-associated MUC-1. 27332727 2 3 dep epitopes 364:371 arg1 epitopes 364:371 the O-linked hypoglycosylated epitopes Tn and sialyl-Tn 334:388 the O-linked hypoglycosylated epitopes Tn and sialyl-Tn on cancer-associated MUC-1 334:415 In this issue of Immunity, June and colleagues demonstrate the broad antitumor efficacy of a newly-designed CAR targeting the O-linked hypoglycosylated epitopes Tn and sialyl-Tn on cancer-associated MUC-1. 27332727 2 3 dep epitopes 364:371 arg1 sialyl-Tn 380:388 sialyl-Tn 380:388 sialyl-Tn 380:388 In this issue of Immunity, June and colleagues demonstrate the broad antitumor efficacy of a newly-designed CAR targeting the O-linked hypoglycosylated epitopes Tn and sialyl-Tn on cancer-associated MUC-1. 27332727 2 4 theme antitumor 281:289 arg1 efficacy 291:298 the broad antitumor efficacy 271:298 the broad antitumor efficacy of a newly-designed CAR targeting the O-linked hypoglycosylated epitopes Tn and sialyl-Tn on cancer-associated MUC-1 271:415 In this issue of Immunity, June and colleagues demonstrate the broad antitumor efficacy of a newly-designed CAR targeting the O-linked hypoglycosylated epitopes Tn and sialyl-Tn on cancer-associated MUC-1. 27332727 2 5 theme hypoglycosylated 347:362 arg1 Tn 373:374 Tn 373:374 Tn 373:374 In this issue of Immunity, June and colleagues demonstrate the broad antitumor efficacy of a newly-designed CAR targeting the O-linked hypoglycosylated epitopes Tn and sialyl-Tn on cancer-associated MUC-1. 27332727 2 5 theme hypoglycosylated 347:362 arg1 epitopes 364:371 the O-linked hypoglycosylated epitopes Tn and sialyl-Tn 334:388 the O-linked hypoglycosylated epitopes Tn and sialyl-Tn on cancer-associated MUC-1 334:415 In this issue of Immunity, June and colleagues demonstrate the broad antitumor efficacy of a newly-designed CAR targeting the O-linked hypoglycosylated epitopes Tn and sialyl-Tn on cancer-associated MUC-1. 27332727 2 5 theme hypoglycosylated 347:362 arg1 sialyl-Tn 380:388 sialyl-Tn 380:388 sialyl-Tn 380:388 In this issue of Immunity, June and colleagues demonstrate the broad antitumor efficacy of a newly-designed CAR targeting the O-linked hypoglycosylated epitopes Tn and sialyl-Tn on cancer-associated MUC-1. 27332727 2 6 theme broad 275:279 arg1 efficacy 291:298 the broad antitumor efficacy 271:298 the broad antitumor efficacy of a newly-designed CAR targeting the O-linked hypoglycosylated epitopes Tn and sialyl-Tn on cancer-associated MUC-1 271:415 In this issue of Immunity, June and colleagues demonstrate the broad antitumor efficacy of a newly-designed CAR targeting the O-linked hypoglycosylated epitopes Tn and sialyl-Tn on cancer-associated MUC-1. 27332727 2 7 theme cancer-associated 393:409 arg1 MUC-1 411:415 cancer-associated MUC-1 393:415 cancer-associated MUC-1 393:415 In this issue of Immunity, June and colleagues demonstrate the broad antitumor efficacy of a newly-designed CAR targeting the O-linked hypoglycosylated epitopes Tn and sialyl-Tn on cancer-associated MUC-1. 27332727 2 8 from epitopes 364:371 arg1 MUC-1 411:415 cancer-associated MUC-1 393:415 cancer-associated MUC-1 393:415 In this issue of Immunity, June and colleagues demonstrate the broad antitumor efficacy of a newly-designed CAR targeting the O-linked hypoglycosylated epitopes Tn and sialyl-Tn on cancer-associated MUC-1. 27332727 1 9 theme Engineering 74:84 arg1 T cells 86:92 Engineering T cells 74:92 Engineering T cells with chimeric antigen receptors (CARs) 74:131 Engineering T cells with chimeric antigen receptors (CARs) has demonstrated remarkable success in eradicating hematological malignancies. 27332727 1 10 theme eradicating 172:182 arg1 malignancies 198:209 eradicating hematological malignancies 172:209 eradicating hematological malignancies 172:209 Engineering T cells with chimeric antigen receptors (CARs) has demonstrated remarkable success in eradicating hematological malignancies. 27332727 0 11 theme Driving 0:6 arg1 CARs 8:11 Driving CARs 0:11 Driving CARs into Sweet Roads: Targeting Glycosylated Antigens in Cancer. 0:72 Driving CARs into Sweet Roads: Targeting Glycosylated Antigens in Cancer. 27332727 2 12 theme newly-designed 305:318 arg1 CAR 320:322 a newly-designed CAR 303:322 a newly-designed CAR targeting the O-linked hypoglycosylated epitopes Tn and sialyl-Tn on cancer-associated MUC-1 303:415 In this issue of Immunity, June and colleagues demonstrate the broad antitumor efficacy of a newly-designed CAR targeting the O-linked hypoglycosylated epitopes Tn and sialyl-Tn on cancer-associated MUC-1. 27332727 1 13 theme hematological 184:196 arg1 malignancies 198:209 eradicating hematological malignancies 172:209 eradicating hematological malignancies 172:209 Engineering T cells with chimeric antigen receptors (CARs) has demonstrated remarkable success in eradicating hematological malignancies. 27332727 0 14 theme Sweet 18:22 arg1 Roads 24:28 Sweet Roads 18:28 Sweet Roads 18:28 Driving CARs into Sweet Roads: Targeting Glycosylated Antigens in Cancer. 27332727 1 15 with T cells 86:92 arg1 CARs 127:130 CARs 127:130 CARs 127:130 Engineering T cells with chimeric antigen receptors (CARs) has demonstrated remarkable success in eradicating hematological malignancies. 27332727 1 15 with T cells 86:92 arg1 receptors 116:124 chimeric antigen receptors 99:124 chimeric antigen receptors (CARs) 99:131 Engineering T cells with chimeric antigen receptors (CARs) has demonstrated remarkable success in eradicating hematological malignancies. 27332727 1 16 theme chimeric 99:106 arg1 CARs 127:130 CARs 127:130 CARs 127:130 Engineering T cells with chimeric antigen receptors (CARs) has demonstrated remarkable success in eradicating hematological malignancies. 27332727 1 16 theme chimeric 99:106 arg1 receptors 116:124 chimeric antigen receptors 99:124 chimeric antigen receptors (CARs) 99:131 Engineering T cells with chimeric antigen receptors (CARs) has demonstrated remarkable success in eradicating hematological malignancies. 27332727 0 17 dep Glycosylated 41:52 arg1 Targeting 31:39 Targeting 31:39 Targeting 31:39 Driving CARs into Sweet Roads: Targeting Glycosylated Antigens in Cancer. 27332727 2 18 theme Immunity 229:236 arg1 issue 220:224 this issue 215:224 this issue of Immunity 215:236 In this issue of Immunity, June and colleagues demonstrate the broad antitumor efficacy of a newly-designed CAR targeting the O-linked hypoglycosylated epitopes Tn and sialyl-Tn on cancer-associated MUC-1. 27332727 0 19 theme Glycosylated 41:52 arg1 Antigens 54:61 Targeting Glycosylated Antigens 31:61 Driving CARs into Sweet Roads: Targeting Glycosylated Antigens in Cancer. 0:72 Driving CARs into Sweet Roads: Targeting Glycosylated Antigens in Cancer. 27332727 0 20 from Antigens 54:61 arg1 Cancer 66:71 Cancer 66:71 Cancer 66:71 Driving CARs into Sweet Roads: Targeting Glycosylated Antigens in Cancer. 27332727 1 21 theme antigen 108:114 arg1 CARs 127:130 CARs 127:130 CARs 127:130 Engineering T cells with chimeric antigen receptors (CARs) has demonstrated remarkable success in eradicating hematological malignancies. 27332727 1 21 theme antigen 108:114 arg1 receptors 116:124 chimeric antigen receptors 99:124 chimeric antigen receptors (CARs) 99:131 Engineering T cells with chimeric antigen receptors (CARs) has demonstrated remarkable success in eradicating hematological malignancies. 27332727 2 22 gly hypoglycosylated 347:362 arg1 Tn 373:374 Tn 373:374 Tn 373:374 In this issue of Immunity, June and colleagues demonstrate the broad antitumor efficacy of a newly-designed CAR targeting the O-linked hypoglycosylated epitopes Tn and sialyl-Tn on cancer-associated MUC-1. 27332727 2 22 gly hypoglycosylated 347:362 arg1 epitopes 364:371 the O-linked hypoglycosylated epitopes Tn and sialyl-Tn 334:388 the O-linked hypoglycosylated epitopes Tn and sialyl-Tn on cancer-associated MUC-1 334:415 In this issue of Immunity, June and colleagues demonstrate the broad antitumor efficacy of a newly-designed CAR targeting the O-linked hypoglycosylated epitopes Tn and sialyl-Tn on cancer-associated MUC-1. 27332727 2 22 gly hypoglycosylated 347:362 arg1 sialyl-Tn 380:388 sialyl-Tn 380:388 sialyl-Tn 380:388 In this issue of Immunity, June and colleagues demonstrate the broad antitumor efficacy of a newly-designed CAR targeting the O-linked hypoglycosylated epitopes Tn and sialyl-Tn on cancer-associated MUC-1. 27332727 2 23 theme O-linked 338:345 arg1 Tn 373:374 Tn 373:374 Tn 373:374 In this issue of Immunity, June and colleagues demonstrate the broad antitumor efficacy of a newly-designed CAR targeting the O-linked hypoglycosylated epitopes Tn and sialyl-Tn on cancer-associated MUC-1. 27332727 2 23 theme O-linked 338:345 arg1 epitopes 364:371 the O-linked hypoglycosylated epitopes Tn and sialyl-Tn 334:388 the O-linked hypoglycosylated epitopes Tn and sialyl-Tn on cancer-associated MUC-1 334:415 In this issue of Immunity, June and colleagues demonstrate the broad antitumor efficacy of a newly-designed CAR targeting the O-linked hypoglycosylated epitopes Tn and sialyl-Tn on cancer-associated MUC-1. 27332727 2 23 theme O-linked 338:345 arg1 sialyl-Tn 380:388 sialyl-Tn 380:388 sialyl-Tn 380:388 In this issue of Immunity, June and colleagues demonstrate the broad antitumor efficacy of a newly-designed CAR targeting the O-linked hypoglycosylated epitopes Tn and sialyl-Tn on cancer-associated MUC-1. 27332727 0 24 dep CARs 8:11 arg1 Antigens 54:61 Targeting Glycosylated Antigens 31:61 Driving CARs into Sweet Roads: Targeting Glycosylated Antigens in Cancer. 0:72 Driving CARs into Sweet Roads: Targeting Glycosylated Antigens in Cancer. 27332727 1 25 from success 161:167 arg1 malignancies 198:209 eradicating hematological malignancies 172:209 eradicating hematological malignancies 172:209 Engineering T cells with chimeric antigen receptors (CARs) has demonstrated remarkable success in eradicating hematological malignancies. 25461760 3 0 theme glycans 315:321 arg1 similarities 290:301 the similarities 286:301 the similarities of N-linked glycans decorating glycoproteins in the haloarchaea Haloferax volcanii and Halobacterium salinarum 286:412 With this in mind, the similarities of N-linked glycans decorating glycoproteins in the haloarchaea Haloferax volcanii and Halobacterium salinarum directed a series of bioinformatics, genetic, and biochemical experiments designed to describe that Hbt. 25461760 4 1 link N-linked 582:589 arg1 oligosaccharides 591:606 the two N-linked oligosaccharides 574:606 the two N-linked oligosaccharides 574:606 salinarum pathway responsible for biogenesis of one of the two N-linked oligosaccharides described in this species. 25461760 13 2 theme N-glycosylation 1426:1440 arg1 pathway 1442:1448 an N-glycosylation pathway 1423:1448 an N-glycosylation pathway 1423:1448 Based on the results obtained in this study, the first description of an N-glycosylation pathway in Hbt. 25461760 7 3 theme genes 904:908 arg1 VNG1048G-VNG1068G 911:927 VNG1048G-VNG1068G 911:927 VNG1048G-VNG1068G 911:927 salinarum also contains a group of clustered homologous genes (VNG1048G-VNG1068G). 25461760 7 3 theme genes 904:908 arg1 genes 904:908 clustered homologous genes 883:908 clustered homologous genes (VNG1048G-VNG1068G) 883:928 salinarum also contains a group of clustered homologous genes (VNG1048G-VNG1068G). 25461760 7 3 theme genes 904:908 arg1 group 874:878 a group 872:878 a group of clustered homologous genes (VNG1048G-VNG1068G) 872:928 salinarum also contains a group of clustered homologous genes (VNG1048G-VNG1068G). 25461760 4 4 theme salinarum 519:527 arg1 pathway 529:535 salinarum pathway 519:535 salinarum pathway responsible for biogenesis of one of the two N-linked oligosaccharides 519:606 salinarum pathway responsible for biogenesis of one of the two N-linked oligosaccharides described in this species. 25461760 13 5 theme pathway 1442:1448 arg1 description 1408:1418 the first description 1398:1418 the first description of an N-glycosylation pathway in Hbt 1398:1455 Based on the results obtained in this study, the first description of an N-glycosylation pathway in Hbt. 25461760 3 6 theme Haloferax 367:375 arg1 volcanii 377:384 the haloarchaea Haloferax volcanii 351:384 the haloarchaea Haloferax volcanii 351:384 With this in mind, the similarities of N-linked glycans decorating glycoproteins in the haloarchaea Haloferax volcanii and Halobacterium salinarum directed a series of bioinformatics, genetic, and biochemical experiments designed to describe that Hbt. 25461760 4 7 theme responsible 537:547 arg1 pathway 529:535 salinarum pathway 519:535 salinarum pathway responsible for biogenesis of one of the two N-linked oligosaccharides 519:606 salinarum pathway responsible for biogenesis of one of the two N-linked oligosaccharides described in this species. 25461760 13 8 from description 1408:1418 arg1 Hbt 1453:1455 Hbt 1453:1455 Hbt 1453:1455 Based on the results obtained in this study, the first description of an N-glycosylation pathway in Hbt. 25461760 1 9 theme Genomic 66:72 arg1 analysis 74:81 Genomic analysis 66:81 Genomic analysis 66:81 Genomic analysis points to N-glycosylation as being a common posttranslational modification in Archaea. 25461760 7 10 theme clustered 883:891 arg1 VNG1048G-VNG1068G 911:927 VNG1048G-VNG1068G 911:927 VNG1048G-VNG1068G 911:927 salinarum also contains a group of clustered homologous genes (VNG1048G-VNG1068G). 25461760 7 10 theme clustered 883:891 arg1 genes 904:908 clustered homologous genes 883:908 clustered homologous genes (VNG1048G-VNG1068G) 883:928 salinarum also contains a group of clustered homologous genes (VNG1048G-VNG1068G). 25461760 12 11 from confirmation 1175:1186 arg1 host 1137:1140 the native host 1126:1140 the native host 1126:1140 salinarum genes in the native host, as well as in vitro biochemical confirmation of the predicted functions of several of the products of these genes provided further support for assignments made following bioinformatics and genetic experiments. 25461760 12 12 theme salinarum 1107:1115 arg1 genes 1117:1121 salinarum genes 1107:1121 salinarum genes in the native host, as well as in vitro biochemical confirmation of the predicted functions of several of the products of these genes 1107:1255 salinarum genes in the native host, as well as in vitro biochemical confirmation of the predicted functions of several of the products of these genes provided further support for assignments made following bioinformatics and genetic experiments. 25461760 12 13 theme native 1130:1135 arg1 host 1137:1140 the native host 1126:1140 the native host 1126:1140 salinarum genes in the native host, as well as in vitro biochemical confirmation of the predicted functions of several of the products of these genes provided further support for assignments made following bioinformatics and genetic experiments. 25461760 3 14 theme haloarchaea 355:365 arg1 volcanii 377:384 the haloarchaea Haloferax volcanii 351:384 the haloarchaea Haloferax volcanii 351:384 With this in mind, the similarities of N-linked glycans decorating glycoproteins in the haloarchaea Haloferax volcanii and Halobacterium salinarum directed a series of bioinformatics, genetic, and biochemical experiments designed to describe that Hbt. 25461760 12 15 theme products 1233:1240 arg1 several 1218:1224 several 1218:1224 several 1218:1224 salinarum genes in the native host, as well as in vitro biochemical confirmation of the predicted functions of several of the products of these genes provided further support for assignments made following bioinformatics and genetic experiments. 25461760 1 16 from modification 145:156 arg1 Archaea 161:167 Archaea 161:167 Archaea 161:167 Genomic analysis points to N-glycosylation as being a common posttranslational modification in Archaea. 25461760 6 17 theme responsible 718:728 arg1 volcanii 646:653 volcanii 646:653 volcanii 646:653 volcanii, where agl (archaeal glycosylation) genes that encode proteins responsible for the assembly and attachment of a pentasaccharide to target protein Asn residues are clustered in the genome, Hbt. 25461760 6 17 theme responsible 718:728 arg1 proteins 709:716 proteins 709:716 proteins responsible for the assembly and attachment of a pentasaccharide to target protein Asn residues 709:812 volcanii, where agl (archaeal glycosylation) genes that encode proteins responsible for the assembly and attachment of a pentasaccharide to target protein Asn residues are clustered in the genome, Hbt. 25461760 6 17 theme responsible 718:728 arg1 genes 691:695 agl (archaeal glycosylation) genes 662:695 agl (archaeal glycosylation) genes that encode proteins responsible for the assembly and attachment of a pentasaccharide to target protein Asn residues 662:812 volcanii, where agl (archaeal glycosylation) genes that encode proteins responsible for the assembly and attachment of a pentasaccharide to target protein Asn residues are clustered in the genome, Hbt. 25461760 12 18 theme predicted 1195:1203 arg1 functions 1205:1213 the predicted functions 1191:1213 the predicted functions of several of the products of these genes 1191:1255 salinarum genes in the native host, as well as in vitro biochemical confirmation of the predicted functions of several of the products of these genes provided further support for assignments made following bioinformatics and genetic experiments. 25461760 13 19 theme first 1402:1406 arg1 description 1408:1418 the first description 1398:1418 the first description of an N-glycosylation pathway in Hbt 1398:1455 Based on the results obtained in this study, the first description of an N-glycosylation pathway in Hbt. 25461760 3 20 theme N-linked 306:313 arg1 glycans 315:321 N-linked glycans 306:321 N-linked glycans decorating glycoproteins 306:346 With this in mind, the similarities of N-linked glycans decorating glycoproteins in the haloarchaea Haloferax volcanii and Halobacterium salinarum directed a series of bioinformatics, genetic, and biochemical experiments designed to describe that Hbt. 25461760 6 21 dep Hbt 843:845 arg1 volcanii 646:653 volcanii 646:653 volcanii 646:653 volcanii, where agl (archaeal glycosylation) genes that encode proteins responsible for the assembly and attachment of a pentasaccharide to target protein Asn residues are clustered in the genome, Hbt. 25461760 6 21 dep Hbt 843:845 arg1 proteins 709:716 proteins 709:716 proteins responsible for the assembly and attachment of a pentasaccharide to target protein Asn residues 709:812 volcanii, where agl (archaeal glycosylation) genes that encode proteins responsible for the assembly and attachment of a pentasaccharide to target protein Asn residues are clustered in the genome, Hbt. 25461760 6 21 dep Hbt 843:845 arg1 genes 691:695 agl (archaeal glycosylation) genes 662:695 agl (archaeal glycosylation) genes that encode proteins responsible for the assembly and attachment of a pentasaccharide to target protein Asn residues 662:812 volcanii, where agl (archaeal glycosylation) genes that encode proteins responsible for the assembly and attachment of a pentasaccharide to target protein Asn residues are clustered in the genome, Hbt. 25461760 10 22 theme lost 1056:1059 arg1 activity 1061:1068 the lost activity 1052:1068 the lost activity 1052:1068 volcanii mutant strains deleted of the homologous sequence restored the lost activity. 25461760 6 23 theme Asn 801:803 arg1 residues 805:812 target protein Asn residues 786:812 target protein Asn residues 786:812 volcanii, where agl (archaeal glycosylation) genes that encode proteins responsible for the assembly and attachment of a pentasaccharide to target protein Asn residues are clustered in the genome, Hbt. 25461760 3 24 theme genetic 451:457 arg1 experiments 476:486 genetic, and biochemical experiments 451:486 genetic, and biochemical experiments designed to describe that Hbt 451:516 With this in mind, the similarities of N-linked glycans decorating glycoproteins in the haloarchaea Haloferax volcanii and Halobacterium salinarum directed a series of bioinformatics, genetic, and biochemical experiments designed to describe that Hbt. 25461760 3 24 theme genetic 451:457 arg1 series 425:430 a series 423:430 a series of bioinformatics 423:448 With this in mind, the similarities of N-linked glycans decorating glycoproteins in the haloarchaea Haloferax volcanii and Halobacterium salinarum directed a series of bioinformatics, genetic, and biochemical experiments designed to describe that Hbt. 25461760 6 25 theme protein 793:799 arg1 residues 805:812 target protein Asn residues 786:812 target protein Asn residues 786:812 volcanii, where agl (archaeal glycosylation) genes that encode proteins responsible for the assembly and attachment of a pentasaccharide to target protein Asn residues are clustered in the genome, Hbt. 25461760 3 26 theme Halobacterium 390:402 arg1 salinarum 404:412 Halobacterium salinarum 390:412 Halobacterium salinarum 390:412 With this in mind, the similarities of N-linked glycans decorating glycoproteins in the haloarchaea Haloferax volcanii and Halobacterium salinarum directed a series of bioinformatics, genetic, and biochemical experiments designed to describe that Hbt. 25461760 4 27 theme oligosaccharides 591:606 arg1 one 567:569 one 567:569 one 567:569 salinarum pathway responsible for biogenesis of one of the two N-linked oligosaccharides described in this species. 25461760 4 27 theme oligosaccharides 591:606 arg1 oligosaccharides 591:606 the two N-linked oligosaccharides 574:606 the two N-linked oligosaccharides 574:606 salinarum pathway responsible for biogenesis of one of the two N-linked oligosaccharides described in this species. 25461760 8 28 theme Hbt 953:955 arg1 Introduction 931:942 Introduction 931:942 Introduction of these Hbt. 931:956 Introduction of these Hbt. 25461760 12 29 theme functions 1205:1213 arg1 confirmation 1175:1186 biochemical confirmation 1163:1186 biochemical confirmation of the predicted functions of several of the products of these genes 1163:1255 salinarum genes in the native host, as well as in vitro biochemical confirmation of the predicted functions of several of the products of these genes provided further support for assignments made following bioinformatics and genetic experiments. 25461760 0 30 theme salinarum 39:47 arg1 N-glycosylation 49:63 Halobacterium salinarum N-glycosylation 25:63 Halobacterium salinarum N-glycosylation 25:63 Deciphering a pathway of Halobacterium salinarum N-glycosylation. 25461760 4 31 theme N-linked 582:589 arg1 oligosaccharides 591:606 the two N-linked oligosaccharides 574:606 the two N-linked oligosaccharides 574:606 salinarum pathway responsible for biogenesis of one of the two N-linked oligosaccharides described in this species. 25461760 11 32 theme Hbt 1102:1104 arg1 transcription 1081:1093 transcription 1081:1093 transcription of the Hbt 1081:1104 Moreover, transcription of the Hbt. 25461760 10 33 theme mutant 993:998 arg1 strains 1000:1006 volcanii mutant strains 984:1006 volcanii mutant strains deleted of the homologous sequence 984:1041 volcanii mutant strains deleted of the homologous sequence restored the lost activity. 25461760 3 34 theme biochemical 464:474 arg1 experiments 476:486 genetic, and biochemical experiments 451:486 genetic, and biochemical experiments designed to describe that Hbt 451:516 With this in mind, the similarities of N-linked glycans decorating glycoproteins in the haloarchaea Haloferax volcanii and Halobacterium salinarum directed a series of bioinformatics, genetic, and biochemical experiments designed to describe that Hbt. 25461760 3 34 theme biochemical 464:474 arg1 series 425:430 a series 423:430 a series of bioinformatics 423:448 With this in mind, the similarities of N-linked glycans decorating glycoproteins in the haloarchaea Haloferax volcanii and Halobacterium salinarum directed a series of bioinformatics, genetic, and biochemical experiments designed to describe that Hbt. 25461760 0 35 theme Halobacterium 25:37 arg1 N-glycosylation 49:63 Halobacterium salinarum N-glycosylation 25:63 Halobacterium salinarum N-glycosylation 25:63 Deciphering a pathway of Halobacterium salinarum N-glycosylation. 25461760 3 36 theme bioinformatics 435:448 arg1 series 425:430 a series 423:430 a series of bioinformatics 423:448 With this in mind, the similarities of N-linked glycans decorating glycoproteins in the haloarchaea Haloferax volcanii and Halobacterium salinarum directed a series of bioinformatics, genetic, and biochemical experiments designed to describe that Hbt. 25461760 3 36 theme bioinformatics 435:448 arg1 experiments 476:486 genetic, and biochemical experiments 451:486 genetic, and biochemical experiments designed to describe that Hbt 451:516 With this in mind, the similarities of N-linked glycans decorating glycoproteins in the haloarchaea Haloferax volcanii and Halobacterium salinarum directed a series of bioinformatics, genetic, and biochemical experiments designed to describe that Hbt. 25461760 6 37 theme target 786:791 arg1 residues 805:812 target protein Asn residues 786:812 target protein Asn residues 786:812 volcanii, where agl (archaeal glycosylation) genes that encode proteins responsible for the assembly and attachment of a pentasaccharide to target protein Asn residues are clustered in the genome, Hbt. 25461760 12 38 theme biochemical 1163:1173 arg1 confirmation 1175:1186 biochemical confirmation 1163:1186 biochemical confirmation of the predicted functions of several of the products of these genes 1163:1255 salinarum genes in the native host, as well as in vitro biochemical confirmation of the predicted functions of several of the products of these genes provided further support for assignments made following bioinformatics and genetic experiments. 25461760 7 39 contain contains 863:870 arg2 group 874:878 a group 872:878 a group of clustered homologous genes (VNG1048G-VNG1068G) 872:928 salinarum also contains a group of clustered homologous genes (VNG1048G-VNG1068G). 25461760 7 39 contain contains 863:870 arg2 VNG1048G-VNG1068G 911:927 VNG1048G-VNG1068G 911:927 VNG1048G-VNG1068G 911:927 salinarum also contains a group of clustered homologous genes (VNG1048G-VNG1068G). 25461760 7 39 contain contains 863:870 arg1 salinarum 848:856 salinarum 848:856 salinarum 848:856 salinarum also contains a group of clustered homologous genes (VNG1048G-VNG1068G). 25461760 7 39 contain contains 863:870 arg2 genes 904:908 clustered homologous genes 883:908 clustered homologous genes (VNG1048G-VNG1068G) 883:928 salinarum also contains a group of clustered homologous genes (VNG1048G-VNG1068G). 25461760 10 40 theme homologous 1023:1032 arg1 sequence 1034:1041 the homologous sequence 1019:1041 the homologous sequence 1019:1041 volcanii mutant strains deleted of the homologous sequence restored the lost activity. 25461760 1 41 theme common 120:125 arg1 modification 145:156 a common posttranslational modification 118:156 a common posttranslational modification in Archaea 118:167 Genomic analysis points to N-glycosylation as being a common posttranslational modification in Archaea. 25461760 0 42 theme N-glycosylation 49:63 arg1 pathway 14:20 a pathway 12:20 a pathway of Halobacterium salinarum N-glycosylation 12:63 Deciphering a pathway of Halobacterium salinarum N-glycosylation. 25461760 3 43 gly glycoproteins 334:346 arg1 glycoproteins 334:346 glycoproteins 334:346 glycoproteins 334:346 With this in mind, the similarities of N-linked glycans decorating glycoproteins in the haloarchaea Haloferax volcanii and Halobacterium salinarum directed a series of bioinformatics, genetic, and biochemical experiments designed to describe that Hbt. 25461760 12 44 dep provided 1257:1264 arg1 support 1274:1280 support 1274:1280 provided further support for assignments made following bioinformatics and genetic experiments 1257:1350 salinarum genes in the native host, as well as in vitro biochemical confirmation of the predicted functions of several of the products of these genes provided further support for assignments made following bioinformatics and genetic experiments. 25461760 6 45 theme pentasaccharide 767:781 arg1 attachment 751:760 attachment 751:760 attachment 751:760 volcanii, where agl (archaeal glycosylation) genes that encode proteins responsible for the assembly and attachment of a pentasaccharide to target protein Asn residues are clustered in the genome, Hbt. 25461760 6 45 theme pentasaccharide 767:781 arg1 assembly 738:745 assembly 738:745 assembly 738:745 volcanii, where agl (archaeal glycosylation) genes that encode proteins responsible for the assembly and attachment of a pentasaccharide to target protein Asn residues are clustered in the genome, Hbt. 25461760 1 46 theme posttranslational 127:143 arg1 modification 145:156 a common posttranslational modification 118:156 a common posttranslational modification in Archaea 118:167 Genomic analysis points to N-glycosylation as being a common posttranslational modification in Archaea. 25461760 6 47 theme glycosylation 676:688 arg1 genes 691:695 agl (archaeal glycosylation) genes 662:695 agl (archaeal glycosylation) genes that encode proteins responsible for the assembly and attachment of a pentasaccharide to target protein Asn residues 662:812 volcanii, where agl (archaeal glycosylation) genes that encode proteins responsible for the assembly and attachment of a pentasaccharide to target protein Asn residues are clustered in the genome, Hbt. 25461760 6 47 theme glycosylation 676:688 arg1 proteins 709:716 proteins 709:716 proteins responsible for the assembly and attachment of a pentasaccharide to target protein Asn residues 709:812 volcanii, where agl (archaeal glycosylation) genes that encode proteins responsible for the assembly and attachment of a pentasaccharide to target protein Asn residues are clustered in the genome, Hbt. 25461760 6 47 theme glycosylation 676:688 arg1 volcanii 646:653 volcanii 646:653 volcanii 646:653 volcanii, where agl (archaeal glycosylation) genes that encode proteins responsible for the assembly and attachment of a pentasaccharide to target protein Asn residues are clustered in the genome, Hbt. 25461760 4 48 theme one 567:569 arg1 biogenesis 553:562 biogenesis 553:562 biogenesis of one of the two N-linked oligosaccharides 553:606 salinarum pathway responsible for biogenesis of one of the two N-linked oligosaccharides described in this species. 25461760 2 49 theme N-glycosylation 209:223 arg1 pathways 188:195 pathways 188:195 pathways of archaeal N-glycosylation 188:223 To date, however, pathways of archaeal N-glycosylation have only been described for few species. 25461760 12 50 theme genetic 1332:1338 arg1 experiments 1340:1350 genetic experiments 1332:1350 genetic experiments 1332:1350 salinarum genes in the native host, as well as in vitro biochemical confirmation of the predicted functions of several of the products of these genes provided further support for assignments made following bioinformatics and genetic experiments. 25461760 12 51 theme genes 1251:1255 arg1 products 1233:1240 the products 1229:1240 the products of these genes 1229:1255 salinarum genes in the native host, as well as in vitro biochemical confirmation of the predicted functions of several of the products of these genes provided further support for assignments made following bioinformatics and genetic experiments. 25461760 6 52 theme archaeal 667:674 arg1 genes 691:695 agl (archaeal glycosylation) genes 662:695 agl (archaeal glycosylation) genes that encode proteins responsible for the assembly and attachment of a pentasaccharide to target protein Asn residues 662:812 volcanii, where agl (archaeal glycosylation) genes that encode proteins responsible for the assembly and attachment of a pentasaccharide to target protein Asn residues are clustered in the genome, Hbt. 25461760 6 52 theme archaeal 667:674 arg1 proteins 709:716 proteins 709:716 proteins responsible for the assembly and attachment of a pentasaccharide to target protein Asn residues 709:812 volcanii, where agl (archaeal glycosylation) genes that encode proteins responsible for the assembly and attachment of a pentasaccharide to target protein Asn residues are clustered in the genome, Hbt. 25461760 6 52 theme archaeal 667:674 arg1 volcanii 646:653 volcanii 646:653 volcanii 646:653 volcanii, where agl (archaeal glycosylation) genes that encode proteins responsible for the assembly and attachment of a pentasaccharide to target protein Asn residues are clustered in the genome, Hbt. 25461760 2 53 theme archaeal 200:207 arg1 N-glycosylation 209:223 archaeal N-glycosylation 200:223 archaeal N-glycosylation 200:223 To date, however, pathways of archaeal N-glycosylation have only been described for few species. 25461760 3 54 link N-linked 306:313 arg1 glycans 315:321 N-linked glycans 306:321 N-linked glycans decorating glycoproteins 306:346 With this in mind, the similarities of N-linked glycans decorating glycoproteins in the haloarchaea Haloferax volcanii and Halobacterium salinarum directed a series of bioinformatics, genetic, and biochemical experiments designed to describe that Hbt. 25461760 3 55 from similarities 290:301 arg1 salinarum 404:412 Halobacterium salinarum 390:412 Halobacterium salinarum 390:412 With this in mind, the similarities of N-linked glycans decorating glycoproteins in the haloarchaea Haloferax volcanii and Halobacterium salinarum directed a series of bioinformatics, genetic, and biochemical experiments designed to describe that Hbt. 25461760 3 55 from similarities 290:301 arg1 volcanii 377:384 the haloarchaea Haloferax volcanii 351:384 the haloarchaea Haloferax volcanii 351:384 With this in mind, the similarities of N-linked glycans decorating glycoproteins in the haloarchaea Haloferax volcanii and Halobacterium salinarum directed a series of bioinformatics, genetic, and biochemical experiments designed to describe that Hbt. 25461760 6 56 dep assembly 738:745 arg1 the 734:736 the 734:736 the 734:736 volcanii, where agl (archaeal glycosylation) genes that encode proteins responsible for the assembly and attachment of a pentasaccharide to target protein Asn residues are clustered in the genome, Hbt. 25461760 12 57 theme several 1218:1224 arg1 functions 1205:1213 the predicted functions 1191:1213 the predicted functions of several of the products of these genes 1191:1255 salinarum genes in the native host, as well as in vitro biochemical confirmation of the predicted functions of several of the products of these genes provided further support for assignments made following bioinformatics and genetic experiments. 25461760 6 58 theme agl 662:664 arg1 genes 691:695 agl (archaeal glycosylation) genes 662:695 agl (archaeal glycosylation) genes that encode proteins responsible for the assembly and attachment of a pentasaccharide to target protein Asn residues 662:812 volcanii, where agl (archaeal glycosylation) genes that encode proteins responsible for the assembly and attachment of a pentasaccharide to target protein Asn residues are clustered in the genome, Hbt. 25461760 6 58 theme agl 662:664 arg1 proteins 709:716 proteins 709:716 proteins responsible for the assembly and attachment of a pentasaccharide to target protein Asn residues 709:812 volcanii, where agl (archaeal glycosylation) genes that encode proteins responsible for the assembly and attachment of a pentasaccharide to target protein Asn residues are clustered in the genome, Hbt. 25461760 6 58 theme agl 662:664 arg1 volcanii 646:653 volcanii 646:653 volcanii 646:653 volcanii, where agl (archaeal glycosylation) genes that encode proteins responsible for the assembly and attachment of a pentasaccharide to target protein Asn residues are clustered in the genome, Hbt. 25461760 2 59 theme few 254:256 arg1 species 258:264 few species 254:264 few species 254:264 To date, however, pathways of archaeal N-glycosylation have only been described for few species. 25461760 7 60 theme homologous 893:902 arg1 VNG1048G-VNG1068G 911:927 VNG1048G-VNG1068G 911:927 VNG1048G-VNG1068G 911:927 salinarum also contains a group of clustered homologous genes (VNG1048G-VNG1068G). 25461760 7 60 theme homologous 893:902 arg1 genes 904:908 clustered homologous genes 883:908 clustered homologous genes (VNG1048G-VNG1068G) 883:928 salinarum also contains a group of clustered homologous genes (VNG1048G-VNG1068G). 24502800 5 0 dep cavity 889:894 arg1 the 885:887 the 885:887 the 885:887 RESULTS At two weeks after operation, the region of the exposed pulp formed a layer of reparative dentin bridge sealing the communication between the cavity and pulp chamber. 24502800 9 1 theme SIBLINGs 1187:1194 arg1 expression 1173:1182 the expression 1169:1182 the expression of SIBLINGs 1169:1194 RepD showed certain similarities to ReaD in the expression of SIBLINGs. 24502800 4 2 from sialoprotein 580:591 arg1 RepD 650:653 RepD 650:653 RepD 650:653 The immunolocalization of four SIBLINGs, dentin matrix protein 1 (DMP1), dentin sialoprotein (DSP), bone sialoprotein (BSP), and osteopontin (OPN) in RepD, was analyzed in comparison with reactionary dentin (ReaD) and primary dentin (PD). 24502800 4 3 theme primary 718:724 arg1 PD 734:735 PD 734:735 PD 734:735 The immunolocalization of four SIBLINGs, dentin matrix protein 1 (DMP1), dentin sialoprotein (DSP), bone sialoprotein (BSP), and osteopontin (OPN) in RepD, was analyzed in comparison with reactionary dentin (ReaD) and primary dentin (PD). 24502800 4 3 theme primary 718:724 arg1 dentin 726:731 primary dentin 718:731 primary dentin (PD) 718:736 The immunolocalization of four SIBLINGs, dentin matrix protein 1 (DMP1), dentin sialoprotein (DSP), bone sialoprotein (BSP), and osteopontin (OPN) in RepD, was analyzed in comparison with reactionary dentin (ReaD) and primary dentin (PD). 24502800 1 4 theme Integrin-Binding 174:189 arg1 SIBLINGs 222:229 SIBLINGs 222:229 SIBLINGs 222:229 AIM To analyze the expression and distribution of Small Integrin-Binding LIgand N-linked Glycoproteins (SIBLINGs) in reparative dentin (RepD). 24502800 1 4 theme Integrin-Binding 174:189 arg1 Glycoproteins 207:219 Small Integrin-Binding LIgand N-linked Glycoproteins 168:219 Small Integrin-Binding LIgand N-linked Glycoproteins (SIBLINGs) 168:230 AIM To analyze the expression and distribution of Small Integrin-Binding LIgand N-linked Glycoproteins (SIBLINGs) in reparative dentin (RepD). 24502800 5 5 from weeks 754:758 arg1 RESULTS 739:745 RESULTS 739:745 RESULTS At two weeks after operation, the region of the exposed pulp 739:806 RESULTS At two weeks after operation, the region of the exposed pulp formed a layer of reparative dentin bridge sealing the communication between the cavity and pulp chamber. 24502800 0 6 theme molars 110:115 arg1 dentin 96:101 the reparative dentin 81:101 the reparative dentin of rat molars 81:115 Expression of Small Integrin-Binding LIgand N-linked Glycoproteins (SIBLINGs) in the reparative dentin of rat molars. 24502800 5 7 theme pulp 900:903 arg1 chamber 905:911 pulp chamber 900:911 pulp chamber 900:911 RESULTS At two weeks after operation, the region of the exposed pulp formed a layer of reparative dentin bridge sealing the communication between the cavity and pulp chamber. 24502800 4 8 dep dentin 700:705 arg1 ReaD 708:711 ReaD 708:711 ReaD 708:711 The immunolocalization of four SIBLINGs, dentin matrix protein 1 (DMP1), dentin sialoprotein (DSP), bone sialoprotein (BSP), and osteopontin (OPN) in RepD, was analyzed in comparison with reactionary dentin (ReaD) and primary dentin (PD). 24502800 3 9 with molars 424:429 arg1 capping 441:447 pulp capping 436:447 pulp capping 436:447 The molars with pulp capping were extracted at postoperative 1, 2, and 4 weeks. 24502800 11 10 from expression 1321:1330 arg1 RepD 1350:1353 RepD 1350:1353 RepD 1350:1353 The expression of BSP and OPN in RepD indicates that the odontoblast-like cells were attempting to produce a hard tissue at a very rapid pace. 24502800 7 11 theme lower 1038:1042 arg1 levels 1044:1049 lower levels 1038:1049 lower levels of DMP1 and DSP 1038:1065 At postoperative 2 and 4 weeks, RepD had lower levels of DMP1 and DSP than PD. 24502800 1 12 from distribution 152:163 arg1 RepD 254:257 RepD 254:257 RepD 254:257 AIM To analyze the expression and distribution of Small Integrin-Binding LIgand N-linked Glycoproteins (SIBLINGs) in reparative dentin (RepD). 24502800 1 12 from distribution 152:163 arg1 dentin 246:251 reparative dentin 235:251 reparative dentin (RepD) 235:258 AIM To analyze the expression and distribution of Small Integrin-Binding LIgand N-linked Glycoproteins (SIBLINGs) in reparative dentin (RepD). 24502800 10 13 theme reduced 1213:1219 arg1 levels 1221:1226 The reduced levels 1209:1226 CONCLUSIONS The reduced levels of DMP1 and DSP 1197:1242 CONCLUSIONS The reduced levels of DMP1 and DSP may be associated with the decreased number of dentinal tubules in RepD. 24502800 4 14 with comparison 672:681 arg1 PD 734:735 PD 734:735 PD 734:735 The immunolocalization of four SIBLINGs, dentin matrix protein 1 (DMP1), dentin sialoprotein (DSP), bone sialoprotein (BSP), and osteopontin (OPN) in RepD, was analyzed in comparison with reactionary dentin (ReaD) and primary dentin (PD). 24502800 4 14 with comparison 672:681 arg1 dentin 700:705 reactionary dentin 688:705 reactionary dentin (ReaD) 688:712 The immunolocalization of four SIBLINGs, dentin matrix protein 1 (DMP1), dentin sialoprotein (DSP), bone sialoprotein (BSP), and osteopontin (OPN) in RepD, was analyzed in comparison with reactionary dentin (ReaD) and primary dentin (PD). 24502800 4 14 with comparison 672:681 arg1 dentin 726:731 primary dentin 718:731 primary dentin (PD) 718:736 The immunolocalization of four SIBLINGs, dentin matrix protein 1 (DMP1), dentin sialoprotein (DSP), bone sialoprotein (BSP), and osteopontin (OPN) in RepD, was analyzed in comparison with reactionary dentin (ReaD) and primary dentin (PD). 24502800 1 15 from expression 137:146 arg1 RepD 254:257 RepD 254:257 RepD 254:257 AIM To analyze the expression and distribution of Small Integrin-Binding LIgand N-linked Glycoproteins (SIBLINGs) in reparative dentin (RepD). 24502800 1 15 from expression 137:146 arg1 dentin 246:251 reparative dentin 235:251 reparative dentin (RepD) 235:258 AIM To analyze the expression and distribution of Small Integrin-Binding LIgand N-linked Glycoproteins (SIBLINGs) in reparative dentin (RepD). 24502800 0 16 from Expression 0:9 arg1 dentin 96:101 the reparative dentin 81:101 the reparative dentin of rat molars 81:115 Expression of Small Integrin-Binding LIgand N-linked Glycoproteins (SIBLINGs) in the reparative dentin of rat molars. 24502800 0 17 theme reparative 85:94 arg1 dentin 96:101 the reparative dentin 81:101 the reparative dentin of rat molars 81:115 Expression of Small Integrin-Binding LIgand N-linked Glycoproteins (SIBLINGs) in the reparative dentin of rat molars. 24502800 5 18 theme pulp 803:806 arg1 operation 766:774 operation 766:774 operation 766:774 RESULTS At two weeks after operation, the region of the exposed pulp formed a layer of reparative dentin bridge sealing the communication between the cavity and pulp chamber. 24502800 5 18 theme pulp 803:806 arg1 region 781:786 the region 777:786 the region of the exposed pulp 777:806 RESULTS At two weeks after operation, the region of the exposed pulp formed a layer of reparative dentin bridge sealing the communication between the cavity and pulp chamber. 24502800 2 19 theme calcium 359:365 arg1 agent 377:381 a calcium hydroxide agent 357:381 a calcium hydroxide agent 357:381 METHODOLOGY Cavities on the mesial surfaces of rat molars were prepared to expose the pulp, and a calcium hydroxide agent was applied to cap the exposed pulp. 24502800 10 20 dep CONCLUSIONS 1197:1207 arg1 levels 1221:1226 The reduced levels 1209:1226 CONCLUSIONS The reduced levels of DMP1 and DSP 1197:1242 CONCLUSIONS The reduced levels of DMP1 and DSP may be associated with the decreased number of dentinal tubules in RepD. 24502800 2 21 theme exposed 406:412 arg1 pulp 414:417 the exposed pulp 402:417 the exposed pulp 402:417 METHODOLOGY Cavities on the mesial surfaces of rat molars were prepared to expose the pulp, and a calcium hydroxide agent was applied to cap the exposed pulp. 24502800 1 22 dep expression 137:146 arg1 the 133:135 the 133:135 the 133:135 AIM To analyze the expression and distribution of Small Integrin-Binding LIgand N-linked Glycoproteins (SIBLINGs) in reparative dentin (RepD). 24502800 12 23 theme hard 1650:1653 arg1 tissue 1655:1660 a hard tissue 1648:1660 a hard tissue that is an intermediate between dentin and bone 1648:1708 These findings suggest that in response to the surgical injury, the newly differentiated odontoblast-like cells altered their synthesis of the dentinogenesis-related proteins and produced a hard tissue that is an intermediate between dentin and bone. 24502800 12 23 theme hard 1650:1653 arg1 intermediate 1673:1684 an intermediate 1670:1684 an intermediate between dentin and bone 1670:1708 These findings suggest that in response to the surgical injury, the newly differentiated odontoblast-like cells altered their synthesis of the dentinogenesis-related proteins and produced a hard tissue that is an intermediate between dentin and bone. 24502800 4 24 from osteopontin 629:639 arg1 RepD 650:653 RepD 650:653 RepD 650:653 The immunolocalization of four SIBLINGs, dentin matrix protein 1 (DMP1), dentin sialoprotein (DSP), bone sialoprotein (BSP), and osteopontin (OPN) in RepD, was analyzed in comparison with reactionary dentin (ReaD) and primary dentin (PD). 24502800 0 25 theme Small 14:18 arg1 SIBLINGs 68:75 SIBLINGs 68:75 SIBLINGs 68:75 Expression of Small Integrin-Binding LIgand N-linked Glycoproteins (SIBLINGs) in the reparative dentin of rat molars. 24502800 0 25 theme Small 14:18 arg1 Glycoproteins 53:65 Small Integrin-Binding LIgand N-linked Glycoproteins 14:65 Small Integrin-Binding LIgand N-linked Glycoproteins (SIBLINGs) 14:76 Expression of Small Integrin-Binding LIgand N-linked Glycoproteins (SIBLINGs) in the reparative dentin of rat molars. 24502800 4 26 theme reactionary 688:698 arg1 dentin 700:705 reactionary dentin 688:705 reactionary dentin (ReaD) 688:712 The immunolocalization of four SIBLINGs, dentin matrix protein 1 (DMP1), dentin sialoprotein (DSP), bone sialoprotein (BSP), and osteopontin (OPN) in RepD, was analyzed in comparison with reactionary dentin (ReaD) and primary dentin (PD). 24502800 0 27 theme LIgand 37:42 arg1 SIBLINGs 68:75 SIBLINGs 68:75 SIBLINGs 68:75 Expression of Small Integrin-Binding LIgand N-linked Glycoproteins (SIBLINGs) in the reparative dentin of rat molars. 24502800 0 27 theme LIgand 37:42 arg1 Glycoproteins 53:65 Small Integrin-Binding LIgand N-linked Glycoproteins 14:65 Small Integrin-Binding LIgand N-linked Glycoproteins (SIBLINGs) 14:76 Expression of Small Integrin-Binding LIgand N-linked Glycoproteins (SIBLINGs) in the reparative dentin of rat molars. 24502800 12 28 theme proteins 1626:1633 arg1 synthesis 1586:1594 their synthesis 1580:1594 their synthesis of the dentinogenesis-related proteins 1580:1633 These findings suggest that in response to the surgical injury, the newly differentiated odontoblast-like cells altered their synthesis of the dentinogenesis-related proteins and produced a hard tissue that is an intermediate between dentin and bone. 24502800 12 29 theme differentiated 1534:1547 arg1 cells 1566:1570 the newly differentiated odontoblast-like cells 1524:1570 the newly differentiated odontoblast-like cells 1524:1570 These findings suggest that in response to the surgical injury, the newly differentiated odontoblast-like cells altered their synthesis of the dentinogenesis-related proteins and produced a hard tissue that is an intermediate between dentin and bone. 24502800 7 30 dep postoperative 1000:1012 arg1 2 1014:1014 2 1014:1014 2 1014:1014 At postoperative 2 and 4 weeks, RepD had lower levels of DMP1 and DSP than PD. 24502800 4 31 from protein 555:561 arg1 RepD 650:653 RepD 650:653 RepD 650:653 The immunolocalization of four SIBLINGs, dentin matrix protein 1 (DMP1), dentin sialoprotein (DSP), bone sialoprotein (BSP), and osteopontin (OPN) in RepD, was analyzed in comparison with reactionary dentin (ReaD) and primary dentin (PD). 24502800 11 32 theme OPN 1343:1345 arg1 expression 1321:1330 The expression 1317:1330 The expression of BSP and OPN in RepD 1317:1353 The expression of BSP and OPN in RepD indicates that the odontoblast-like cells were attempting to produce a hard tissue at a very rapid pace. 24502800 0 33 theme Glycoproteins 53:65 arg1 Expression 0:9 Expression 0:9 Expression of Small Integrin-Binding LIgand N-linked Glycoproteins (SIBLINGs) in the reparative dentin of rat molars. 0:116 Expression of Small Integrin-Binding LIgand N-linked Glycoproteins (SIBLINGs) in the reparative dentin of rat molars. 24502800 11 34 theme BSP 1335:1337 arg1 expression 1321:1330 The expression 1317:1330 The expression of BSP and OPN in RepD 1317:1353 The expression of BSP and OPN in RepD indicates that the odontoblast-like cells were attempting to produce a hard tissue at a very rapid pace. 24502800 2 35 theme molars 312:317 arg1 surfaces 296:303 the mesial surfaces 285:303 the mesial surfaces of rat molars 285:317 METHODOLOGY Cavities on the mesial surfaces of rat molars were prepared to expose the pulp, and a calcium hydroxide agent was applied to cap the exposed pulp. 24502800 4 36 theme dentin 541:546 arg1 protein 555:561 dentin matrix protein 1 541:563 dentin matrix protein 1 (DMP1) 541:570 The immunolocalization of four SIBLINGs, dentin matrix protein 1 (DMP1), dentin sialoprotein (DSP), bone sialoprotein (BSP), and osteopontin (OPN) in RepD, was analyzed in comparison with reactionary dentin (ReaD) and primary dentin (PD). 24502800 4 36 theme dentin 541:546 arg1 DMP1 566:569 DMP1 566:569 DMP1 566:569 The immunolocalization of four SIBLINGs, dentin matrix protein 1 (DMP1), dentin sialoprotein (DSP), bone sialoprotein (BSP), and osteopontin (OPN) in RepD, was analyzed in comparison with reactionary dentin (ReaD) and primary dentin (PD). 24502800 4 36 theme dentin 541:546 arg1 immunolocalization 504:521 The immunolocalization 500:521 The immunolocalization of four SIBLINGs 500:538 The immunolocalization of four SIBLINGs, dentin matrix protein 1 (DMP1), dentin sialoprotein (DSP), bone sialoprotein (BSP), and osteopontin (OPN) in RepD, was analyzed in comparison with reactionary dentin (ReaD) and primary dentin (PD). 24502800 11 37 theme rapid 1448:1452 arg1 pace 1454:1457 a very rapid pace 1441:1457 a very rapid pace 1441:1457 The expression of BSP and OPN in RepD indicates that the odontoblast-like cells were attempting to produce a hard tissue at a very rapid pace. 24502800 6 38 from tubules 923:929 arg1 RepD 934:937 RepD 934:937 RepD 934:937 Dentinal tubules in RepD were more irregular in shape and fewer in number than PD. 24502800 5 39 theme dentin 837:842 arg1 bridge 844:849 reparative dentin bridge 826:849 reparative dentin bridge sealing the communication between the cavity and pulp chamber 826:911 RESULTS At two weeks after operation, the region of the exposed pulp formed a layer of reparative dentin bridge sealing the communication between the cavity and pulp chamber. 24502800 10 40 theme dentinal 1291:1298 arg1 tubules 1300:1306 dentinal tubules 1291:1306 dentinal tubules in RepD 1291:1314 CONCLUSIONS The reduced levels of DMP1 and DSP may be associated with the decreased number of dentinal tubules in RepD. 24502800 7 41 contain had 1034:1036 arg1 RepD 1029:1032 RepD 1029:1032 RepD 1029:1032 At postoperative 2 and 4 weeks, RepD had lower levels of DMP1 and DSP than PD. 24502800 7 41 contain had 1034:1036 arg2 levels 1044:1049 lower levels 1038:1049 lower levels of DMP1 and DSP 1038:1065 At postoperative 2 and 4 weeks, RepD had lower levels of DMP1 and DSP than PD. 24502800 11 42 theme odontoblast-like 1374:1389 arg1 cells 1391:1395 the odontoblast-like cells 1370:1395 the odontoblast-like cells 1370:1395 The expression of BSP and OPN in RepD indicates that the odontoblast-like cells were attempting to produce a hard tissue at a very rapid pace. 24502800 4 43 theme SIBLINGs 531:538 arg1 sialoprotein 580:591 dentin sialoprotein 573:591 dentin sialoprotein (DSP) 573:597 The immunolocalization of four SIBLINGs, dentin matrix protein 1 (DMP1), dentin sialoprotein (DSP), bone sialoprotein (BSP), and osteopontin (OPN) in RepD, was analyzed in comparison with reactionary dentin (ReaD) and primary dentin (PD). 24502800 4 43 theme SIBLINGs 531:538 arg1 sialoprotein 605:616 bone sialoprotein 600:616 bone sialoprotein (BSP) 600:622 The immunolocalization of four SIBLINGs, dentin matrix protein 1 (DMP1), dentin sialoprotein (DSP), bone sialoprotein (BSP), and osteopontin (OPN) in RepD, was analyzed in comparison with reactionary dentin (ReaD) and primary dentin (PD). 24502800 4 43 theme SIBLINGs 531:538 arg1 protein 555:561 dentin matrix protein 1 541:563 dentin matrix protein 1 (DMP1) 541:570 The immunolocalization of four SIBLINGs, dentin matrix protein 1 (DMP1), dentin sialoprotein (DSP), bone sialoprotein (BSP), and osteopontin (OPN) in RepD, was analyzed in comparison with reactionary dentin (ReaD) and primary dentin (PD). 24502800 4 43 theme SIBLINGs 531:538 arg1 osteopontin 629:639 osteopontin 629:639 osteopontin (OPN) 629:645 The immunolocalization of four SIBLINGs, dentin matrix protein 1 (DMP1), dentin sialoprotein (DSP), bone sialoprotein (BSP), and osteopontin (OPN) in RepD, was analyzed in comparison with reactionary dentin (ReaD) and primary dentin (PD). 24502800 4 43 theme SIBLINGs 531:538 arg1 immunolocalization 504:521 The immunolocalization 500:521 The immunolocalization of four SIBLINGs 500:538 The immunolocalization of four SIBLINGs, dentin matrix protein 1 (DMP1), dentin sialoprotein (DSP), bone sialoprotein (BSP), and osteopontin (OPN) in RepD, was analyzed in comparison with reactionary dentin (ReaD) and primary dentin (PD). 24502800 2 44 theme METHODOLOGY 261:271 arg1 Cavities 273:280 METHODOLOGY Cavities 261:280 METHODOLOGY Cavities on the mesial surfaces of rat molars 261:317 METHODOLOGY Cavities on the mesial surfaces of rat molars were prepared to expose the pulp, and a calcium hydroxide agent was applied to cap the exposed pulp. 24502800 4 45 theme dentin 573:578 arg1 sialoprotein 580:591 dentin sialoprotein 573:591 dentin sialoprotein (DSP) 573:597 The immunolocalization of four SIBLINGs, dentin matrix protein 1 (DMP1), dentin sialoprotein (DSP), bone sialoprotein (BSP), and osteopontin (OPN) in RepD, was analyzed in comparison with reactionary dentin (ReaD) and primary dentin (PD). 24502800 4 45 theme dentin 573:578 arg1 immunolocalization 504:521 The immunolocalization 500:521 The immunolocalization of four SIBLINGs 500:538 The immunolocalization of four SIBLINGs, dentin matrix protein 1 (DMP1), dentin sialoprotein (DSP), bone sialoprotein (BSP), and osteopontin (OPN) in RepD, was analyzed in comparison with reactionary dentin (ReaD) and primary dentin (PD). 24502800 4 45 theme dentin 573:578 arg1 DSP 594:596 DSP 594:596 DSP 594:596 The immunolocalization of four SIBLINGs, dentin matrix protein 1 (DMP1), dentin sialoprotein (DSP), bone sialoprotein (BSP), and osteopontin (OPN) in RepD, was analyzed in comparison with reactionary dentin (ReaD) and primary dentin (PD). 24502800 1 46 theme Small 168:172 arg1 SIBLINGs 222:229 SIBLINGs 222:229 SIBLINGs 222:229 AIM To analyze the expression and distribution of Small Integrin-Binding LIgand N-linked Glycoproteins (SIBLINGs) in reparative dentin (RepD). 24502800 1 46 theme Small 168:172 arg1 Glycoproteins 207:219 Small Integrin-Binding LIgand N-linked Glycoproteins 168:219 Small Integrin-Binding LIgand N-linked Glycoproteins (SIBLINGs) 168:230 AIM To analyze the expression and distribution of Small Integrin-Binding LIgand N-linked Glycoproteins (SIBLINGs) in reparative dentin (RepD). 24502800 0 47 link N-linked 44:51 arg1 SIBLINGs 68:75 SIBLINGs 68:75 SIBLINGs 68:75 Expression of Small Integrin-Binding LIgand N-linked Glycoproteins (SIBLINGs) in the reparative dentin of rat molars. 24502800 0 47 link N-linked 44:51 arg1 Glycoproteins 53:65 Small Integrin-Binding LIgand N-linked Glycoproteins 14:65 Small Integrin-Binding LIgand N-linked Glycoproteins (SIBLINGs) 14:76 Expression of Small Integrin-Binding LIgand N-linked Glycoproteins (SIBLINGs) in the reparative dentin of rat molars. 24502800 2 48 theme mesial 289:294 arg1 surfaces 296:303 the mesial surfaces 285:303 the mesial surfaces of rat molars 285:317 METHODOLOGY Cavities on the mesial surfaces of rat molars were prepared to expose the pulp, and a calcium hydroxide agent was applied to cap the exposed pulp. 24502800 1 49 theme LIgand 191:196 arg1 SIBLINGs 222:229 SIBLINGs 222:229 SIBLINGs 222:229 AIM To analyze the expression and distribution of Small Integrin-Binding LIgand N-linked Glycoproteins (SIBLINGs) in reparative dentin (RepD). 24502800 1 49 theme LIgand 191:196 arg1 Glycoproteins 207:219 Small Integrin-Binding LIgand N-linked Glycoproteins 168:219 Small Integrin-Binding LIgand N-linked Glycoproteins (SIBLINGs) 168:230 AIM To analyze the expression and distribution of Small Integrin-Binding LIgand N-linked Glycoproteins (SIBLINGs) in reparative dentin (RepD). 24502800 1 50 theme Glycoproteins 207:219 arg1 distribution 152:163 distribution 152:163 distribution 152:163 AIM To analyze the expression and distribution of Small Integrin-Binding LIgand N-linked Glycoproteins (SIBLINGs) in reparative dentin (RepD). 24502800 1 50 theme Glycoproteins 207:219 arg1 expression 137:146 expression 137:146 expression 137:146 AIM To analyze the expression and distribution of Small Integrin-Binding LIgand N-linked Glycoproteins (SIBLINGs) in reparative dentin (RepD). 24502800 8 51 attach present 1093:1099 arg2 BSP 1076:1078 BSP 1076:1078 BSP 1076:1078 BSP and OPN were present in RepD, but not in PD. 24502800 8 51 attach present 1093:1099 arg1 PD 1121:1122 PD 1121:1122 PD 1121:1122 BSP and OPN were present in RepD, but not in PD. 24502800 8 51 attach present 1093:1099 arg1 RepD 1104:1107 RepD 1104:1107 RepD 1104:1107 BSP and OPN were present in RepD, but not in PD. 24502800 8 51 attach present 1093:1099 arg2 OPN 1084:1086 OPN 1084:1086 OPN 1084:1086 BSP and OPN were present in RepD, but not in PD. 24502800 2 52 from Cavities 273:280 arg1 surfaces 296:303 the mesial surfaces 285:303 the mesial surfaces of rat molars 285:317 METHODOLOGY Cavities on the mesial surfaces of rat molars were prepared to expose the pulp, and a calcium hydroxide agent was applied to cap the exposed pulp. 24502800 4 53 theme bone 600:603 arg1 BSP 619:621 BSP 619:621 BSP 619:621 The immunolocalization of four SIBLINGs, dentin matrix protein 1 (DMP1), dentin sialoprotein (DSP), bone sialoprotein (BSP), and osteopontin (OPN) in RepD, was analyzed in comparison with reactionary dentin (ReaD) and primary dentin (PD). 24502800 4 53 theme bone 600:603 arg1 sialoprotein 605:616 bone sialoprotein 600:616 bone sialoprotein (BSP) 600:622 The immunolocalization of four SIBLINGs, dentin matrix protein 1 (DMP1), dentin sialoprotein (DSP), bone sialoprotein (BSP), and osteopontin (OPN) in RepD, was analyzed in comparison with reactionary dentin (ReaD) and primary dentin (PD). 24502800 4 53 theme bone 600:603 arg1 immunolocalization 504:521 The immunolocalization 500:521 The immunolocalization of four SIBLINGs 500:538 The immunolocalization of four SIBLINGs, dentin matrix protein 1 (DMP1), dentin sialoprotein (DSP), bone sialoprotein (BSP), and osteopontin (OPN) in RepD, was analyzed in comparison with reactionary dentin (ReaD) and primary dentin (PD). 24502800 5 54 theme exposed 795:801 arg1 pulp 803:806 the exposed pulp 791:806 the exposed pulp 791:806 RESULTS At two weeks after operation, the region of the exposed pulp formed a layer of reparative dentin bridge sealing the communication between the cavity and pulp chamber. 24502800 10 55 from number 1281:1286 arg1 RepD 1311:1314 RepD 1311:1314 RepD 1311:1314 CONCLUSIONS The reduced levels of DMP1 and DSP may be associated with the decreased number of dentinal tubules in RepD. 24502800 1 56 link N-linked 198:205 arg1 SIBLINGs 222:229 SIBLINGs 222:229 SIBLINGs 222:229 AIM To analyze the expression and distribution of Small Integrin-Binding LIgand N-linked Glycoproteins (SIBLINGs) in reparative dentin (RepD). 24502800 1 56 link N-linked 198:205 arg1 Glycoproteins 207:219 Small Integrin-Binding LIgand N-linked Glycoproteins 168:219 Small Integrin-Binding LIgand N-linked Glycoproteins (SIBLINGs) 168:230 AIM To analyze the expression and distribution of Small Integrin-Binding LIgand N-linked Glycoproteins (SIBLINGs) in reparative dentin (RepD). 24502800 2 57 theme rat 308:310 arg1 molars 312:317 rat molars 308:317 rat molars 308:317 METHODOLOGY Cavities on the mesial surfaces of rat molars were prepared to expose the pulp, and a calcium hydroxide agent was applied to cap the exposed pulp. 24502800 0 58 theme rat 106:108 arg1 molars 110:115 rat molars 106:115 rat molars 106:115 Expression of Small Integrin-Binding LIgand N-linked Glycoproteins (SIBLINGs) in the reparative dentin of rat molars. 24502800 1 59 theme N-linked 198:205 arg1 SIBLINGs 222:229 SIBLINGs 222:229 SIBLINGs 222:229 AIM To analyze the expression and distribution of Small Integrin-Binding LIgand N-linked Glycoproteins (SIBLINGs) in reparative dentin (RepD). 24502800 1 59 theme N-linked 198:205 arg1 Glycoproteins 207:219 Small Integrin-Binding LIgand N-linked Glycoproteins 168:219 Small Integrin-Binding LIgand N-linked Glycoproteins (SIBLINGs) 168:230 AIM To analyze the expression and distribution of Small Integrin-Binding LIgand N-linked Glycoproteins (SIBLINGs) in reparative dentin (RepD). 24502800 6 60 theme Dentinal 914:921 arg1 tubules 923:929 Dentinal tubules 914:929 Dentinal tubules in RepD 914:937 Dentinal tubules in RepD were more irregular in shape and fewer in number than PD. 24502800 10 61 theme DMP1 1231:1234 arg1 levels 1221:1226 The reduced levels 1209:1226 CONCLUSIONS The reduced levels of DMP1 and DSP 1197:1242 CONCLUSIONS The reduced levels of DMP1 and DSP may be associated with the decreased number of dentinal tubules in RepD. 24502800 12 62 dep injury 1516:1521 arg1 response 1491:1498 response 1491:1498 response 1491:1498 These findings suggest that in response to the surgical injury, the newly differentiated odontoblast-like cells altered their synthesis of the dentinogenesis-related proteins and produced a hard tissue that is an intermediate between dentin and bone. 24502800 8 63 from RepD 1104:1107 arg1 present 1093:1099 present 1093:1099 present 1093:1099 BSP and OPN were present in RepD, but not in PD. 24502800 0 64 theme Integrin-Binding 20:35 arg1 SIBLINGs 68:75 SIBLINGs 68:75 SIBLINGs 68:75 Expression of Small Integrin-Binding LIgand N-linked Glycoproteins (SIBLINGs) in the reparative dentin of rat molars. 24502800 0 64 theme Integrin-Binding 20:35 arg1 Glycoproteins 53:65 Small Integrin-Binding LIgand N-linked Glycoproteins 14:65 Small Integrin-Binding LIgand N-linked Glycoproteins (SIBLINGs) 14:76 Expression of Small Integrin-Binding LIgand N-linked Glycoproteins (SIBLINGs) in the reparative dentin of rat molars. 24502800 12 65 theme dentinogenesis-related 1603:1624 arg1 proteins 1626:1633 the dentinogenesis-related proteins 1599:1633 the dentinogenesis-related proteins 1599:1633 These findings suggest that in response to the surgical injury, the newly differentiated odontoblast-like cells altered their synthesis of the dentinogenesis-related proteins and produced a hard tissue that is an intermediate between dentin and bone. 24502800 8 66 from present 1093:1099 arg1 PD 1121:1122 PD 1121:1122 PD 1121:1122 BSP and OPN were present in RepD, but not in PD. 24502800 8 66 from present 1093:1099 arg1 RepD 1104:1107 RepD 1104:1107 RepD 1104:1107 BSP and OPN were present in RepD, but not in PD. 24502800 0 67 theme N-linked 44:51 arg1 SIBLINGs 68:75 SIBLINGs 68:75 SIBLINGs 68:75 Expression of Small Integrin-Binding LIgand N-linked Glycoproteins (SIBLINGs) in the reparative dentin of rat molars. 24502800 0 67 theme N-linked 44:51 arg1 Glycoproteins 53:65 Small Integrin-Binding LIgand N-linked Glycoproteins 14:65 Small Integrin-Binding LIgand N-linked Glycoproteins (SIBLINGs) 14:76 Expression of Small Integrin-Binding LIgand N-linked Glycoproteins (SIBLINGs) in the reparative dentin of rat molars. 24502800 5 68 theme bridge 844:849 arg1 layer 817:821 a layer 815:821 a layer of reparative dentin bridge sealing the communication between the cavity and pulp chamber 815:911 RESULTS At two weeks after operation, the region of the exposed pulp formed a layer of reparative dentin bridge sealing the communication between the cavity and pulp chamber. 24502800 10 69 theme DSP 1240:1242 arg1 levels 1221:1226 The reduced levels 1209:1226 CONCLUSIONS The reduced levels of DMP1 and DSP 1197:1242 CONCLUSIONS The reduced levels of DMP1 and DSP may be associated with the decreased number of dentinal tubules in RepD. 24502800 11 70 theme hard 1426:1429 arg1 tissue 1431:1436 a hard tissue 1424:1436 a hard tissue 1424:1436 The expression of BSP and OPN in RepD indicates that the odontoblast-like cells were attempting to produce a hard tissue at a very rapid pace. 24502800 6 71 from irregular 949:957 arg1 shape 962:966 shape 962:966 shape 962:966 Dentinal tubules in RepD were more irregular in shape and fewer in number than PD. 24502800 2 72 theme hydroxide 367:375 arg1 agent 377:381 a calcium hydroxide agent 357:381 a calcium hydroxide agent 357:381 METHODOLOGY Cavities on the mesial surfaces of rat molars were prepared to expose the pulp, and a calcium hydroxide agent was applied to cap the exposed pulp. 24502800 8 73 located present 1093:1099 arg2 BSP 1076:1078 BSP 1076:1078 BSP 1076:1078 BSP and OPN were present in RepD, but not in PD. 24502800 8 73 located present 1093:1099 arg1 RepD 1104:1107 RepD 1104:1107 RepD 1104:1107 BSP and OPN were present in RepD, but not in PD. 24502800 8 73 located present 1093:1099 arg2 OPN 1084:1086 OPN 1084:1086 OPN 1084:1086 BSP and OPN were present in RepD, but not in PD. 24502800 10 74 from tubules 1300:1306 arg1 RepD 1311:1314 RepD 1311:1314 RepD 1311:1314 CONCLUSIONS The reduced levels of DMP1 and DSP may be associated with the decreased number of dentinal tubules in RepD. 24502800 10 75 theme decreased 1271:1279 arg1 number 1281:1286 the decreased number 1267:1286 the decreased number of dentinal tubules in RepD 1267:1314 CONCLUSIONS The reduced levels of DMP1 and DSP may be associated with the decreased number of dentinal tubules in RepD. 24502800 6 76 from shape 962:966 arg1 irregular 949:957 irregular 949:957 irregular 949:957 Dentinal tubules in RepD were more irregular in shape and fewer in number than PD. 24502800 8 77 from PD 1121:1122 arg1 present 1093:1099 present 1093:1099 present 1093:1099 BSP and OPN were present in RepD, but not in PD. 24502800 9 78 theme certain 1137:1143 arg1 similarities 1145:1156 certain similarities 1137:1156 certain similarities to ReaD in the expression of SIBLINGs 1137:1194 RepD showed certain similarities to ReaD in the expression of SIBLINGs. 24502800 10 79 from RepD 1311:1314 arg1 number 1281:1286 the decreased number 1267:1286 the decreased number of dentinal tubules in RepD 1267:1314 CONCLUSIONS The reduced levels of DMP1 and DSP may be associated with the decreased number of dentinal tubules in RepD. 24502800 12 80 theme odontoblast-like 1549:1564 arg1 cells 1566:1570 the newly differentiated odontoblast-like cells 1524:1570 the newly differentiated odontoblast-like cells 1524:1570 These findings suggest that in response to the surgical injury, the newly differentiated odontoblast-like cells altered their synthesis of the dentinogenesis-related proteins and produced a hard tissue that is an intermediate between dentin and bone. 24502800 7 81 theme DSP 1063:1065 arg1 levels 1044:1049 lower levels 1038:1049 lower levels of DMP1 and DSP 1038:1065 At postoperative 2 and 4 weeks, RepD had lower levels of DMP1 and DSP than PD. 24502800 4 82 theme matrix 548:553 arg1 protein 555:561 dentin matrix protein 1 541:563 dentin matrix protein 1 (DMP1) 541:570 The immunolocalization of four SIBLINGs, dentin matrix protein 1 (DMP1), dentin sialoprotein (DSP), bone sialoprotein (BSP), and osteopontin (OPN) in RepD, was analyzed in comparison with reactionary dentin (ReaD) and primary dentin (PD). 24502800 4 82 theme matrix 548:553 arg1 DMP1 566:569 DMP1 566:569 DMP1 566:569 The immunolocalization of four SIBLINGs, dentin matrix protein 1 (DMP1), dentin sialoprotein (DSP), bone sialoprotein (BSP), and osteopontin (OPN) in RepD, was analyzed in comparison with reactionary dentin (ReaD) and primary dentin (PD). 24502800 4 82 theme matrix 548:553 arg1 immunolocalization 504:521 The immunolocalization 500:521 The immunolocalization of four SIBLINGs 500:538 The immunolocalization of four SIBLINGs, dentin matrix protein 1 (DMP1), dentin sialoprotein (DSP), bone sialoprotein (BSP), and osteopontin (OPN) in RepD, was analyzed in comparison with reactionary dentin (ReaD) and primary dentin (PD). 24502800 3 83 theme pulp 436:439 arg1 capping 441:447 pulp capping 436:447 pulp capping 436:447 The molars with pulp capping were extracted at postoperative 1, 2, and 4 weeks. 24502800 5 84 theme reparative 826:835 arg1 bridge 844:849 reparative dentin bridge 826:849 reparative dentin bridge sealing the communication between the cavity and pulp chamber 826:911 RESULTS At two weeks after operation, the region of the exposed pulp formed a layer of reparative dentin bridge sealing the communication between the cavity and pulp chamber. 24502800 12 85 theme surgical 1507:1514 arg1 injury 1516:1521 the surgical injury 1503:1521 the surgical injury 1503:1521 These findings suggest that in response to the surgical injury, the newly differentiated odontoblast-like cells altered their synthesis of the dentinogenesis-related proteins and produced a hard tissue that is an intermediate between dentin and bone. 24502800 7 86 theme DMP1 1054:1057 arg1 levels 1044:1049 lower levels 1038:1049 lower levels of DMP1 and DSP 1038:1065 At postoperative 2 and 4 weeks, RepD had lower levels of DMP1 and DSP than PD. 24502800 10 87 theme tubules 1300:1306 arg1 number 1281:1286 the decreased number 1267:1286 the decreased number of dentinal tubules in RepD 1267:1314 CONCLUSIONS The reduced levels of DMP1 and DSP may be associated with the decreased number of dentinal tubules in RepD. 24502800 4 88 from sialoprotein 605:616 arg1 RepD 650:653 RepD 650:653 RepD 650:653 The immunolocalization of four SIBLINGs, dentin matrix protein 1 (DMP1), dentin sialoprotein (DSP), bone sialoprotein (BSP), and osteopontin (OPN) in RepD, was analyzed in comparison with reactionary dentin (ReaD) and primary dentin (PD). 24502800 1 89 theme reparative 235:244 arg1 RepD 254:257 RepD 254:257 RepD 254:257 AIM To analyze the expression and distribution of Small Integrin-Binding LIgand N-linked Glycoproteins (SIBLINGs) in reparative dentin (RepD). 24502800 1 89 theme reparative 235:244 arg1 dentin 246:251 reparative dentin 235:251 reparative dentin (RepD) 235:258 AIM To analyze the expression and distribution of Small Integrin-Binding LIgand N-linked Glycoproteins (SIBLINGs) in reparative dentin (RepD). 28414038 0 0 theme marine 82:87 arg1 dipeptide-cyclo 96:110 marine cyclic dipeptide-cyclo 82:110 marine cyclic dipeptide-cyclo(l-leucyl-l-prolyl) 82:129 Modulation of Staphylococcus epidermidis (RP62A) extracellular polymeric layer by marine cyclic dipeptide-cyclo(l-leucyl-l-prolyl) thwarts biofilm formation. 28414038 0 0 theme marine 82:87 arg1 l-leucyl-l-prolyl 112:128 l-leucyl-l-prolyl 112:128 l-leucyl-l-prolyl 112:128 Modulation of Staphylococcus epidermidis (RP62A) extracellular polymeric layer by marine cyclic dipeptide-cyclo(l-leucyl-l-prolyl) thwarts biofilm formation. 28414038 4 1 theme agent 756:760 arg1 effect 725:730 the effect 721:730 the effect of a potent antibiofilm agent cyclic dipeptide, cyclo(l-leucyl-l-prolyl) (CLP), on the EPS modification of S. epidermidis 721:852 Therefore, we assessed the effect of a potent antibiofilm agent cyclic dipeptide, cyclo(l-leucyl-l-prolyl) (CLP), on the EPS modification of S. epidermidis. 28414038 5 2 theme scanning 1023:1030 arg1 microscopes 1041:1051 confocal and scanning electron microscopes 1010:1051 microscopes 1041:1051 The non-bactericidal antibiofilm efficacy of CLP against S. epidermidis was affirmed through quantitative (crystal violet and XTT assays) and qualitative (confocal and scanning electron microscopes) analyses. 28414038 3 3 theme dipeptides 537:546 arg1 prominence 516:525 the prominence 512:525 the prominence of cyclic dipeptides in interfering with biofilms and the associated virulence factors of pathogens 512:625 Recently, the prominence of cyclic dipeptides in interfering with biofilms and the associated virulence factors of pathogens has offered an alternative to eliminate difficult-to-treat infections. 28414038 10 4 theme CLP 1554:1556 arg1 treatment 1558:1566 CLP treatment 1554:1566 CLP treatment 1554:1566 The results of cyclic voltammetry (CV) indicate the decrease of total negative charge of EPS upon CLP treatment, which goes well in accordance with the decrease of eDNA. 28414038 4 5 theme antibiofilm 744:754 arg1 agent 756:760 a potent antibiofilm agent 735:760 a potent antibiofilm agent cyclic dipeptide 735:777 Therefore, we assessed the effect of a potent antibiofilm agent cyclic dipeptide, cyclo(l-leucyl-l-prolyl) (CLP), on the EPS modification of S. epidermidis. 28414038 4 5 theme antibiofilm 744:754 arg1 cyclo 780:784 cyclo 780:784 cyclo(l-leucyl-l-prolyl) (CLP) 780:809 Therefore, we assessed the effect of a potent antibiofilm agent cyclic dipeptide, cyclo(l-leucyl-l-prolyl) (CLP), on the EPS modification of S. epidermidis. 28414038 10 6 theme voltammetry 1478:1488 arg1 results 1460:1466 The results 1456:1466 The results of cyclic voltammetry (CV) 1456:1493 The results of cyclic voltammetry (CV) indicate the decrease of total negative charge of EPS upon CLP treatment, which goes well in accordance with the decrease of eDNA. 28414038 5 7 theme qualitative 997:1007 arg1 analyses 1054:1061 quantitative (crystal violet and XTT assays) and qualitative (confocal and scanning electron microscopes) analyses 948:1061 quantitative (crystal violet and XTT assays) and qualitative (confocal and scanning electron microscopes) analyses 948:1061 The non-bactericidal antibiofilm efficacy of CLP against S. epidermidis was affirmed through quantitative (crystal violet and XTT assays) and qualitative (confocal and scanning electron microscopes) analyses. 28414038 11 8 theme secreted 1735:1742 arg1 EPS 1744:1746 secreted EPS 1735:1746 secreted EPS 1735:1746 Thus, antibiofilm efficacy of CLP lies in its potency to alter the intrinsic functional groups and charge of secreted EPS. 28414038 0 9 theme cyclic 89:94 arg1 dipeptide-cyclo 96:110 marine cyclic dipeptide-cyclo 82:110 marine cyclic dipeptide-cyclo(l-leucyl-l-prolyl) 82:129 Modulation of Staphylococcus epidermidis (RP62A) extracellular polymeric layer by marine cyclic dipeptide-cyclo(l-leucyl-l-prolyl) thwarts biofilm formation. 28414038 0 9 theme cyclic 89:94 arg1 l-leucyl-l-prolyl 112:128 l-leucyl-l-prolyl 112:128 l-leucyl-l-prolyl 112:128 Modulation of Staphylococcus epidermidis (RP62A) extracellular polymeric layer by marine cyclic dipeptide-cyclo(l-leucyl-l-prolyl) thwarts biofilm formation. 28414038 3 10 theme associated 585:594 arg1 factors 606:612 the associated virulence factors 581:612 the associated virulence factors 581:612 Recently, the prominence of cyclic dipeptides in interfering with biofilms and the associated virulence factors of pathogens has offered an alternative to eliminate difficult-to-treat infections. 28414038 2 11 theme key 308:310 arg1 component 312:320 a key component 306:320 a key component of most biofilms 306:337 Extracellular polymeric substance (EPS) is a key component of most biofilms and in pathogens it specifically protects the entrenched-bacterial cells from antibiotics and hosts immune response, and thereby makes the infection ineradicable. 28414038 2 11 theme key 308:310 arg1 substance 287:295 Extracellular polymeric substance 263:295 Extracellular polymeric substance (EPS) 263:301 Extracellular polymeric substance (EPS) is a key component of most biofilms and in pathogens it specifically protects the entrenched-bacterial cells from antibiotics and hosts immune response, and thereby makes the infection ineradicable. 28414038 10 12 theme eDNA 1620:1623 arg1 decrease 1608:1615 the decrease 1604:1615 the decrease of eDNA 1604:1623 The results of cyclic voltammetry (CV) indicate the decrease of total negative charge of EPS upon CLP treatment, which goes well in accordance with the decrease of eDNA. 28414038 5 13 theme antibiofilm 876:886 arg1 efficacy 888:895 The non-bactericidal antibiofilm efficacy 855:895 The non-bactericidal antibiofilm efficacy of CLP against S. epidermidis 855:925 The non-bactericidal antibiofilm efficacy of CLP against S. epidermidis was affirmed through quantitative (crystal violet and XTT assays) and qualitative (confocal and scanning electron microscopes) analyses. 28414038 5 14 theme confocal 1010:1017 arg1 microscopes 1041:1051 confocal and scanning electron microscopes 1010:1051 microscopes 1041:1051 The non-bactericidal antibiofilm efficacy of CLP against S. epidermidis was affirmed through quantitative (crystal violet and XTT assays) and qualitative (confocal and scanning electron microscopes) analyses. 28414038 4 15 from effect 725:730 arg1 modification 823:834 the EPS modification 815:834 the EPS modification of S. epidermidis 815:852 Therefore, we assessed the effect of a potent antibiofilm agent cyclic dipeptide, cyclo(l-leucyl-l-prolyl) (CLP), on the EPS modification of S. epidermidis. 28414038 5 16 theme CLP 900:902 arg1 efficacy 888:895 The non-bactericidal antibiofilm efficacy 855:895 The non-bactericidal antibiofilm efficacy of CLP against S. epidermidis 855:925 The non-bactericidal antibiofilm efficacy of CLP against S. epidermidis was affirmed through quantitative (crystal violet and XTT assays) and qualitative (confocal and scanning electron microscopes) analyses. 28414038 8 17 theme Substantial 1192:1202 arg1 difference 1204:1213 Substantial difference 1192:1213 Substantial difference in the atomic composition and functionality of CLP treated EPS 1192:1276 Substantial difference in the atomic composition and functionality of CLP treated EPS was evident through X-ray photoelectron spectroscopy. 28414038 9 18 theme S. 1364:1365 arg1 epidermidis-EPS 1367:1381 the S. epidermidis-EPS 1360:1381 the S. epidermidis-EPS 1360:1381 Furthermore, CLP dehydrated the S. epidermidis-EPS and altered the acetylated sugars as well as α-glycosidic linkage in it. 28414038 9 19 theme α-glycosidic 1428:1439 arg1 linkage 1441:1447 α-glycosidic linkage 1428:1447 the acetylated sugars as well as α-glycosidic linkage 1395:1447 Furthermore, CLP dehydrated the S. epidermidis-EPS and altered the acetylated sugars as well as α-glycosidic linkage in it. 28414038 6 20 dep potent 1081:1086 arg1 reduce 1098:1103 reduce 1098:1103 to reduce all the EPS components viz 1095:1130 Notably, CLP was potent enough to reduce all the EPS components viz. 28414038 6 21 theme EPS 1113:1115 arg1 components 1117:1126 all the EPS components 1105:1126 all the EPS components viz 1105:1130 Notably, CLP was potent enough to reduce all the EPS components viz. 28414038 8 22 theme treated 1266:1272 arg1 EPS 1274:1276 CLP treated EPS 1262:1276 CLP treated EPS 1262:1276 Substantial difference in the atomic composition and functionality of CLP treated EPS was evident through X-ray photoelectron spectroscopy. 28414038 2 23 theme infection 478:486 arg1 ineradicable 488:499 the infection ineradicable 474:499 the infection ineradicable 474:499 Extracellular polymeric substance (EPS) is a key component of most biofilms and in pathogens it specifically protects the entrenched-bacterial cells from antibiotics and hosts immune response, and thereby makes the infection ineradicable. 28414038 9 24 theme acetylated 1399:1408 arg1 sugars 1410:1415 the acetylated sugars 1395:1415 the acetylated sugars as well as α-glycosidic linkage 1395:1447 Furthermore, CLP dehydrated the S. epidermidis-EPS and altered the acetylated sugars as well as α-glycosidic linkage in it. 28414038 10 25 theme cyclic 1471:1476 arg1 CV 1491:1492 CV 1491:1492 CV 1491:1492 The results of cyclic voltammetry (CV) indicate the decrease of total negative charge of EPS upon CLP treatment, which goes well in accordance with the decrease of eDNA. 28414038 10 25 theme cyclic 1471:1476 arg1 voltammetry 1478:1488 cyclic voltammetry 1471:1488 cyclic voltammetry (CV) 1471:1493 The results of cyclic voltammetry (CV) indicate the decrease of total negative charge of EPS upon CLP treatment, which goes well in accordance with the decrease of eDNA. 28414038 5 26 theme XTT 981:983 arg1 assays 985:990 XTT assays 981:990 XTT assays 981:990 The non-bactericidal antibiofilm efficacy of CLP against S. epidermidis was affirmed through quantitative (crystal violet and XTT assays) and qualitative (confocal and scanning electron microscopes) analyses. 28414038 1 27 theme frequent 197:204 arg1 cause 206:210 the most frequent cause 188:210 the most frequent cause of biofilm mediated implant-associated infections 188:260 Staphylococcus epidermidis is the most frequent cause of biofilm mediated implant-associated infections. 28414038 1 27 theme frequent 197:204 arg1 epidermidis 173:183 Staphylococcus epidermidis 158:183 Staphylococcus epidermidis 158:183 Staphylococcus epidermidis is the most frequent cause of biofilm mediated implant-associated infections. 28414038 8 28 theme EPS 1274:1276 arg1 functionality 1245:1257 functionality 1245:1257 functionality 1245:1257 Substantial difference in the atomic composition and functionality of CLP treated EPS was evident through X-ray photoelectron spectroscopy. 28414038 8 28 theme EPS 1274:1276 arg1 composition 1229:1239 atomic composition 1222:1239 atomic composition 1222:1239 Substantial difference in the atomic composition and functionality of CLP treated EPS was evident through X-ray photoelectron spectroscopy. 28414038 2 29 theme biofilms 330:337 arg1 component 312:320 a key component 306:320 a key component of most biofilms 306:337 Extracellular polymeric substance (EPS) is a key component of most biofilms and in pathogens it specifically protects the entrenched-bacterial cells from antibiotics and hosts immune response, and thereby makes the infection ineradicable. 28414038 2 29 theme biofilms 330:337 arg1 substance 287:295 Extracellular polymeric substance 263:295 Extracellular polymeric substance (EPS) 263:301 Extracellular polymeric substance (EPS) is a key component of most biofilms and in pathogens it specifically protects the entrenched-bacterial cells from antibiotics and hosts immune response, and thereby makes the infection ineradicable. 28414038 0 30 theme epidermidis 29:39 arg1 layer 73:77 Staphylococcus epidermidis (RP62A) extracellular polymeric layer 14:77 Staphylococcus epidermidis (RP62A) extracellular polymeric layer 14:77 Modulation of Staphylococcus epidermidis (RP62A) extracellular polymeric layer by marine cyclic dipeptide-cyclo(l-leucyl-l-prolyl) thwarts biofilm formation. 28414038 10 31 theme charge 1535:1540 arg1 decrease 1508:1515 the decrease 1504:1515 the decrease of total negative charge of EPS 1504:1547 The results of cyclic voltammetry (CV) indicate the decrease of total negative charge of EPS upon CLP treatment, which goes well in accordance with the decrease of eDNA. 28414038 3 32 theme virulence 596:604 arg1 factors 606:612 the associated virulence factors 581:612 the associated virulence factors 581:612 Recently, the prominence of cyclic dipeptides in interfering with biofilms and the associated virulence factors of pathogens has offered an alternative to eliminate difficult-to-treat infections. 28414038 4 33 theme epidermidis 842:852 arg1 modification 823:834 the EPS modification 815:834 the EPS modification of S. epidermidis 815:852 Therefore, we assessed the effect of a potent antibiofilm agent cyclic dipeptide, cyclo(l-leucyl-l-prolyl) (CLP), on the EPS modification of S. epidermidis. 28414038 5 34 theme non-bactericidal 859:874 arg1 efficacy 888:895 The non-bactericidal antibiofilm efficacy 855:895 The non-bactericidal antibiofilm efficacy of CLP against S. epidermidis 855:925 The non-bactericidal antibiofilm efficacy of CLP against S. epidermidis was affirmed through quantitative (crystal violet and XTT assays) and qualitative (confocal and scanning electron microscopes) analyses. 28414038 3 35 theme pathogens 617:625 arg1 factors 606:612 the associated virulence factors 581:612 the associated virulence factors 581:612 Recently, the prominence of cyclic dipeptides in interfering with biofilms and the associated virulence factors of pathogens has offered an alternative to eliminate difficult-to-treat infections. 28414038 3 35 theme pathogens 617:625 arg1 biofilms 568:575 biofilms 568:575 biofilms 568:575 Recently, the prominence of cyclic dipeptides in interfering with biofilms and the associated virulence factors of pathogens has offered an alternative to eliminate difficult-to-treat infections. 28414038 10 36 theme negative 1526:1533 arg1 charge 1535:1540 total negative charge 1520:1540 total negative charge of EPS 1520:1547 The results of cyclic voltammetry (CV) indicate the decrease of total negative charge of EPS upon CLP treatment, which goes well in accordance with the decrease of eDNA. 28414038 11 37 theme intrinsic 1693:1701 arg1 groups 1714:1719 the intrinsic functional groups 1689:1719 the intrinsic functional groups 1689:1719 Thus, antibiofilm efficacy of CLP lies in its potency to alter the intrinsic functional groups and charge of secreted EPS. 28414038 5 38 theme quantitative 948:959 arg1 analyses 1054:1061 quantitative (crystal violet and XTT assays) and qualitative (confocal and scanning electron microscopes) analyses 948:1061 quantitative (crystal violet and XTT assays) and qualitative (confocal and scanning electron microscopes) analyses 948:1061 The non-bactericidal antibiofilm efficacy of CLP against S. epidermidis was affirmed through quantitative (crystal violet and XTT assays) and qualitative (confocal and scanning electron microscopes) analyses. 28414038 1 39 theme biofilm 215:221 arg1 infections 251:260 biofilm mediated implant-associated infections 215:260 biofilm mediated implant-associated infections 215:260 Staphylococcus epidermidis is the most frequent cause of biofilm mediated implant-associated infections. 28414038 5 40 theme crystal 962:968 arg1 violet 970:975 crystal violet 962:975 crystal violet 962:975 The non-bactericidal antibiofilm efficacy of CLP against S. epidermidis was affirmed through quantitative (crystal violet and XTT assays) and qualitative (confocal and scanning electron microscopes) analyses. 28414038 10 41 theme total 1520:1524 arg1 charge 1535:1540 total negative charge 1520:1540 total negative charge of EPS 1520:1547 The results of cyclic voltammetry (CV) indicate the decrease of total negative charge of EPS upon CLP treatment, which goes well in accordance with the decrease of eDNA. 28414038 11 42 theme functional 1703:1712 arg1 groups 1714:1719 the intrinsic functional groups 1689:1719 the intrinsic functional groups 1689:1719 Thus, antibiofilm efficacy of CLP lies in its potency to alter the intrinsic functional groups and charge of secreted EPS. 28414038 2 43 theme polymeric 277:285 arg1 component 312:320 a key component 306:320 a key component of most biofilms 306:337 Extracellular polymeric substance (EPS) is a key component of most biofilms and in pathogens it specifically protects the entrenched-bacterial cells from antibiotics and hosts immune response, and thereby makes the infection ineradicable. 28414038 2 43 theme polymeric 277:285 arg1 EPS 298:300 EPS 298:300 EPS 298:300 Extracellular polymeric substance (EPS) is a key component of most biofilms and in pathogens it specifically protects the entrenched-bacterial cells from antibiotics and hosts immune response, and thereby makes the infection ineradicable. 28414038 2 43 theme polymeric 277:285 arg1 substance 287:295 Extracellular polymeric substance 263:295 Extracellular polymeric substance (EPS) 263:301 Extracellular polymeric substance (EPS) is a key component of most biofilms and in pathogens it specifically protects the entrenched-bacterial cells from antibiotics and hosts immune response, and thereby makes the infection ineradicable. 28414038 1 44 theme mediated 223:230 arg1 infections 251:260 biofilm mediated implant-associated infections 215:260 biofilm mediated implant-associated infections 215:260 Staphylococcus epidermidis is the most frequent cause of biofilm mediated implant-associated infections. 28414038 7 45 theme significant 1173:1183 arg1 level 1185:1189 a significant level 1171:1189 a significant level 1171:1189 polysaccharides, proteins and eDNA to a significant level. 28414038 0 46 theme biofilm 139:145 arg1 formation 147:155 biofilm formation 139:155 biofilm formation 139:155 Modulation of Staphylococcus epidermidis (RP62A) extracellular polymeric layer by marine cyclic dipeptide-cyclo(l-leucyl-l-prolyl) thwarts biofilm formation. 28414038 2 47 theme Extracellular 263:275 arg1 component 312:320 a key component 306:320 a key component of most biofilms 306:337 Extracellular polymeric substance (EPS) is a key component of most biofilms and in pathogens it specifically protects the entrenched-bacterial cells from antibiotics and hosts immune response, and thereby makes the infection ineradicable. 28414038 2 47 theme Extracellular 263:275 arg1 EPS 298:300 EPS 298:300 EPS 298:300 Extracellular polymeric substance (EPS) is a key component of most biofilms and in pathogens it specifically protects the entrenched-bacterial cells from antibiotics and hosts immune response, and thereby makes the infection ineradicable. 28414038 2 47 theme Extracellular 263:275 arg1 substance 287:295 Extracellular polymeric substance 263:295 Extracellular polymeric substance (EPS) 263:301 Extracellular polymeric substance (EPS) is a key component of most biofilms and in pathogens it specifically protects the entrenched-bacterial cells from antibiotics and hosts immune response, and thereby makes the infection ineradicable. 28414038 2 48 from antibiotics 417:427 arg1 cells 406:410 the entrenched-bacterial cells 381:410 the entrenched-bacterial cells from antibiotics 381:427 Extracellular polymeric substance (EPS) is a key component of most biofilms and in pathogens it specifically protects the entrenched-bacterial cells from antibiotics and hosts immune response, and thereby makes the infection ineradicable. 28414038 1 49 theme implant-associated 232:249 arg1 infections 251:260 biofilm mediated implant-associated infections 215:260 biofilm mediated implant-associated infections 215:260 Staphylococcus epidermidis is the most frequent cause of biofilm mediated implant-associated infections. 28414038 0 50 theme extracellular 49:61 arg1 layer 73:77 Staphylococcus epidermidis (RP62A) extracellular polymeric layer 14:77 Staphylococcus epidermidis (RP62A) extracellular polymeric layer 14:77 Modulation of Staphylococcus epidermidis (RP62A) extracellular polymeric layer by marine cyclic dipeptide-cyclo(l-leucyl-l-prolyl) thwarts biofilm formation. 28414038 8 51 dep composition 1229:1239 arg1 the 1218:1220 the 1218:1220 the 1218:1220 Substantial difference in the atomic composition and functionality of CLP treated EPS was evident through X-ray photoelectron spectroscopy. 28414038 5 52 dep quantitative 948:959 arg1 microscopes 1041:1051 confocal and scanning electron microscopes 1010:1051 microscopes 1041:1051 The non-bactericidal antibiofilm efficacy of CLP against S. epidermidis was affirmed through quantitative (crystal violet and XTT assays) and qualitative (confocal and scanning electron microscopes) analyses. 28414038 5 52 dep quantitative 948:959 arg1 violet 970:975 crystal violet 962:975 crystal violet 962:975 The non-bactericidal antibiofilm efficacy of CLP against S. epidermidis was affirmed through quantitative (crystal violet and XTT assays) and qualitative (confocal and scanning electron microscopes) analyses. 28414038 5 52 dep quantitative 948:959 arg1 assays 985:990 XTT assays 981:990 XTT assays 981:990 The non-bactericidal antibiofilm efficacy of CLP against S. epidermidis was affirmed through quantitative (crystal violet and XTT assays) and qualitative (confocal and scanning electron microscopes) analyses. 28414038 4 53 theme dipeptide 769:777 arg1 agent 756:760 a potent antibiofilm agent 735:760 a potent antibiofilm agent cyclic dipeptide 735:777 Therefore, we assessed the effect of a potent antibiofilm agent cyclic dipeptide, cyclo(l-leucyl-l-prolyl) (CLP), on the EPS modification of S. epidermidis. 28414038 4 53 theme dipeptide 769:777 arg1 cyclo 780:784 cyclo 780:784 cyclo(l-leucyl-l-prolyl) (CLP) 780:809 Therefore, we assessed the effect of a potent antibiofilm agent cyclic dipeptide, cyclo(l-leucyl-l-prolyl) (CLP), on the EPS modification of S. epidermidis. 28414038 8 54 from difference 1204:1213 arg1 functionality 1245:1257 functionality 1245:1257 functionality 1245:1257 Substantial difference in the atomic composition and functionality of CLP treated EPS was evident through X-ray photoelectron spectroscopy. 28414038 8 54 from difference 1204:1213 arg1 composition 1229:1239 atomic composition 1222:1239 atomic composition 1222:1239 Substantial difference in the atomic composition and functionality of CLP treated EPS was evident through X-ray photoelectron spectroscopy. 28414038 3 55 theme cyclic 530:535 arg1 dipeptides 537:546 cyclic dipeptides 530:546 cyclic dipeptides 530:546 Recently, the prominence of cyclic dipeptides in interfering with biofilms and the associated virulence factors of pathogens has offered an alternative to eliminate difficult-to-treat infections. 28414038 11 56 theme antibiofilm 1632:1642 arg1 efficacy 1644:1651 antibiofilm efficacy 1632:1651 antibiofilm efficacy of CLP 1632:1658 Thus, antibiofilm efficacy of CLP lies in its potency to alter the intrinsic functional groups and charge of secreted EPS. 28414038 10 57 theme EPS 1545:1547 arg1 charge 1535:1540 total negative charge 1520:1540 total negative charge of EPS 1520:1547 The results of cyclic voltammetry (CV) indicate the decrease of total negative charge of EPS upon CLP treatment, which goes well in accordance with the decrease of eDNA. 28414038 4 58 theme EPS 819:821 arg1 modification 823:834 the EPS modification 815:834 the EPS modification of S. epidermidis 815:852 Therefore, we assessed the effect of a potent antibiofilm agent cyclic dipeptide, cyclo(l-leucyl-l-prolyl) (CLP), on the EPS modification of S. epidermidis. 28414038 3 59 theme difficult-to-treat 667:684 arg1 infections 686:695 difficult-to-treat infections 667:695 difficult-to-treat infections 667:695 Recently, the prominence of cyclic dipeptides in interfering with biofilms and the associated virulence factors of pathogens has offered an alternative to eliminate difficult-to-treat infections. 28414038 2 60 theme most 325:328 arg1 biofilms 330:337 most biofilms 325:337 most biofilms 325:337 Extracellular polymeric substance (EPS) is a key component of most biofilms and in pathogens it specifically protects the entrenched-bacterial cells from antibiotics and hosts immune response, and thereby makes the infection ineradicable. 28414038 1 61 theme infections 251:260 arg1 cause 206:210 the most frequent cause 188:210 the most frequent cause of biofilm mediated implant-associated infections 188:260 Staphylococcus epidermidis is the most frequent cause of biofilm mediated implant-associated infections. 28414038 1 61 theme infections 251:260 arg1 epidermidis 173:183 Staphylococcus epidermidis 158:183 Staphylococcus epidermidis 158:183 Staphylococcus epidermidis is the most frequent cause of biofilm mediated implant-associated infections. 28414038 5 62 theme electron 1032:1039 arg1 microscopes 1041:1051 confocal and scanning electron microscopes 1010:1051 microscopes 1041:1051 The non-bactericidal antibiofilm efficacy of CLP against S. epidermidis was affirmed through quantitative (crystal violet and XTT assays) and qualitative (confocal and scanning electron microscopes) analyses. 28414038 8 63 theme CLP 1262:1264 arg1 EPS 1274:1276 CLP treated EPS 1262:1276 CLP treated EPS 1262:1276 Substantial difference in the atomic composition and functionality of CLP treated EPS was evident through X-ray photoelectron spectroscopy. 28414038 0 64 theme layer 73:77 arg1 Modulation 0:9 Modulation 0:9 Modulation of Staphylococcus epidermidis (RP62A) extracellular polymeric layer by marine cyclic dipeptide-cyclo(l-leucyl-l-prolyl) 0:129 Modulation of Staphylococcus epidermidis (RP62A) extracellular polymeric layer by marine cyclic dipeptide-cyclo(l-leucyl-l-prolyl) thwarts biofilm formation. 28414038 2 65 theme immune 439:444 arg1 response 446:453 immune response 439:453 immune response 439:453 Extracellular polymeric substance (EPS) is a key component of most biofilms and in pathogens it specifically protects the entrenched-bacterial cells from antibiotics and hosts immune response, and thereby makes the infection ineradicable. 28414038 8 66 theme photoelectron 1304:1316 arg1 spectroscopy 1318:1329 X-ray photoelectron spectroscopy 1298:1329 X-ray photoelectron spectroscopy 1298:1329 Substantial difference in the atomic composition and functionality of CLP treated EPS was evident through X-ray photoelectron spectroscopy. 28414038 8 67 theme X-ray 1298:1302 arg1 spectroscopy 1318:1329 X-ray photoelectron spectroscopy 1298:1329 X-ray photoelectron spectroscopy 1298:1329 Substantial difference in the atomic composition and functionality of CLP treated EPS was evident through X-ray photoelectron spectroscopy. 28414038 4 68 theme potent 737:742 arg1 agent 756:760 a potent antibiofilm agent 735:760 a potent antibiofilm agent cyclic dipeptide 735:777 Therefore, we assessed the effect of a potent antibiofilm agent cyclic dipeptide, cyclo(l-leucyl-l-prolyl) (CLP), on the EPS modification of S. epidermidis. 28414038 4 68 theme potent 737:742 arg1 cyclo 780:784 cyclo 780:784 cyclo(l-leucyl-l-prolyl) (CLP) 780:809 Therefore, we assessed the effect of a potent antibiofilm agent cyclic dipeptide, cyclo(l-leucyl-l-prolyl) (CLP), on the EPS modification of S. epidermidis. 28414038 6 69 dep components 1117:1126 arg1 viz 1128:1130 viz 1128:1130 all the EPS components viz 1105:1130 Notably, CLP was potent enough to reduce all the EPS components viz. 28414038 0 70 theme polymeric 63:71 arg1 layer 73:77 Staphylococcus epidermidis (RP62A) extracellular polymeric layer 14:77 Staphylococcus epidermidis (RP62A) extracellular polymeric layer 14:77 Modulation of Staphylococcus epidermidis (RP62A) extracellular polymeric layer by marine cyclic dipeptide-cyclo(l-leucyl-l-prolyl) thwarts biofilm formation. 28414038 11 71 theme CLP 1656:1658 arg1 efficacy 1644:1651 antibiofilm efficacy 1632:1651 antibiofilm efficacy of CLP 1632:1658 Thus, antibiofilm efficacy of CLP lies in its potency to alter the intrinsic functional groups and charge of secreted EPS. 28414038 8 72 theme atomic 1222:1227 arg1 composition 1229:1239 atomic composition 1222:1239 atomic composition 1222:1239 Substantial difference in the atomic composition and functionality of CLP treated EPS was evident through X-ray photoelectron spectroscopy. 28414038 2 73 theme entrenched-bacterial 385:404 arg1 cells 406:410 the entrenched-bacterial cells 381:410 the entrenched-bacterial cells from antibiotics 381:427 Extracellular polymeric substance (EPS) is a key component of most biofilms and in pathogens it specifically protects the entrenched-bacterial cells from antibiotics and hosts immune response, and thereby makes the infection ineradicable. 28414038 11 74 theme EPS 1744:1746 arg1 charge 1725:1730 charge 1725:1730 charge 1725:1730 Thus, antibiofilm efficacy of CLP lies in its potency to alter the intrinsic functional groups and charge of secreted EPS. 28414038 11 74 theme EPS 1744:1746 arg1 potency 1672:1678 its potency to alter the intrinsic functional groups 1668:1719 its potency to alter the intrinsic functional groups 1668:1719 Thus, antibiofilm efficacy of CLP lies in its potency to alter the intrinsic functional groups and charge of secreted EPS. 24899403 0 0 theme vascular 75:82 arg1 proliferation 92:104 vascular cambium proliferation 75:104 vascular cambium proliferation 75:104 Diverse roles of PtrDUF579 proteins in Populus and PtrDUF579-1 function in vascular cambium proliferation during secondary growth. 24899403 2 1 theme cell 334:337 arg1 biosynthesis 344:355 cell wall biosynthesis 334:355 cell wall biosynthesis in Arabidopsis 334:370 Several DUF579 proteins have been found to play a role in cell wall biosynthesis in Arabidopsis, while DUF579 family genes have not yet been systematically investigated in Populus. 24899403 0 2 from roles 8:12 arg1 PtrDUF579-1 51:61 PtrDUF579-1 51:61 PtrDUF579-1 51:61 Diverse roles of PtrDUF579 proteins in Populus and PtrDUF579-1 function in vascular cambium proliferation during secondary growth. 24899403 0 2 from roles 8:12 arg1 Populus 39:45 Populus 39:45 Populus 39:45 Diverse roles of PtrDUF579 proteins in Populus and PtrDUF579-1 function in vascular cambium proliferation during secondary growth. 24899403 7 3 theme Cambium 939:945 arg1 division 952:959 Cambium cell division 939:959 Cambium cell division 939:959 Cambium cell division and xylem tissue growth was inhibited while secondary cell wall formation was unchanged in PtrDUF579-1 suppressed plants. 24899403 1 4 theme function 157:164 arg1 domain 139:144 domain 139:144 domain of unknown function 579 139:168 DUF579 (domain of unknown function 579) family proteins contain a DUF579 domain structure but vary greatly in their overall sequence similarity. 24899403 1 4 theme function 157:164 arg1 function 157:164 unknown function 579 149:168 unknown function 579 149:168 DUF579 (domain of unknown function 579) family proteins contain a DUF579 domain structure but vary greatly in their overall sequence similarity. 24899403 7 5 from unchanged 1039:1047 arg1 plants 1075:1080 PtrDUF579-1 suppressed plants 1052:1080 PtrDUF579-1 suppressed plants 1052:1080 Cambium cell division and xylem tissue growth was inhibited while secondary cell wall formation was unchanged in PtrDUF579-1 suppressed plants. 24899403 8 6 theme fraction 1145:1152 arg1 composition 1119:1129 the composition 1115:1129 the composition of the pectin fraction of the cambium cell wall 1115:1177 Cell walls analysis showed that the composition of the pectin fraction of the cambium cell wall was altered while other polysaccharides were not affected in PtrDUF579-1 suppressed plants. 24899403 6 7 theme PtrDUF579-1 871:881 arg1 expression 883:892 PtrDUF579-1 expression 871:892 PtrDUF579-1 expression 871:892 Suppression of PtrDUF579-1 expression reduced plant height and stem diameter size. 24899403 7 8 theme cell 947:950 arg1 division 952:959 Cambium cell division 939:959 Cambium cell division 939:959 Cambium cell division and xylem tissue growth was inhibited while secondary cell wall formation was unchanged in PtrDUF579-1 suppressed plants. 24899403 2 9 theme DUF579 284:289 arg1 proteins 291:298 Several DUF579 proteins 276:298 Several DUF579 proteins 276:298 Several DUF579 proteins have been found to play a role in cell wall biosynthesis in Arabidopsis, while DUF579 family genes have not yet been systematically investigated in Populus. 24899403 1 10 theme overall 247:253 arg1 similarity 264:273 their overall sequence similarity 241:273 their overall sequence similarity 241:273 DUF579 (domain of unknown function 579) family proteins contain a DUF579 domain structure but vary greatly in their overall sequence similarity. 24899403 0 11 theme cambium 84:90 arg1 proliferation 92:104 vascular cambium proliferation 75:104 vascular cambium proliferation 75:104 Diverse roles of PtrDUF579 proteins in Populus and PtrDUF579-1 function in vascular cambium proliferation during secondary growth. 24899403 9 12 theme expressed 1304:1312 arg1 PtrDUF579-1 1314:1324 cambium expressed PtrDUF579-1 1296:1324 cambium expressed PtrDUF579-1 1296:1324 This observation suggest cambium expressed PtrDUF579-1 may affect cell wall biosynthesis and be involved in cambium cell proliferation in Populus. 24899403 10 13 theme family 1434:1439 arg1 proteins 1441:1448 DUF579 family proteins 1427:1448 DUF579 family proteins 1427:1448 Overall, DUF579 family proteins play a diverse set of roles in Populus. 24899403 2 14 theme Several 276:282 arg1 proteins 291:298 Several DUF579 proteins 276:298 Several DUF579 proteins 276:298 Several DUF579 proteins have been found to play a role in cell wall biosynthesis in Arabidopsis, while DUF579 family genes have not yet been systematically investigated in Populus. 24899403 1 15 theme sequence 255:262 arg1 similarity 264:273 their overall sequence similarity 241:273 their overall sequence similarity 241:273 DUF579 (domain of unknown function 579) family proteins contain a DUF579 domain structure but vary greatly in their overall sequence similarity. 24899403 0 16 theme secondary 113:121 arg1 growth 123:128 secondary growth 113:128 secondary growth 113:128 Diverse roles of PtrDUF579 proteins in Populus and PtrDUF579-1 function in vascular cambium proliferation during secondary growth. 24899403 10 17 theme roles 1472:1476 arg1 set 1465:1467 a diverse set 1455:1467 a diverse set of roles 1455:1476 Overall, DUF579 family proteins play a diverse set of roles in Populus. 24899403 10 17 theme roles 1472:1476 arg1 roles 1472:1476 roles 1472:1476 roles 1472:1476 Overall, DUF579 family proteins play a diverse set of roles in Populus. 24899403 8 18 theme PtrDUF579-1 1240:1250 arg1 plants 1263:1268 PtrDUF579-1 suppressed plants 1240:1268 PtrDUF579-1 suppressed plants 1240:1268 Cell walls analysis showed that the composition of the pectin fraction of the cambium cell wall was altered while other polysaccharides were not affected in PtrDUF579-1 suppressed plants. 24899403 9 19 theme cambium 1296:1302 arg1 PtrDUF579-1 1314:1324 cambium expressed PtrDUF579-1 1296:1324 cambium expressed PtrDUF579-1 1296:1324 This observation suggest cambium expressed PtrDUF579-1 may affect cell wall biosynthesis and be involved in cambium cell proliferation in Populus. 24899403 10 20 theme DUF579 1427:1432 arg1 proteins 1441:1448 DUF579 family proteins 1427:1448 DUF579 family proteins 1427:1448 Overall, DUF579 family proteins play a diverse set of roles in Populus. 24899403 5 21 theme vascular 782:789 arg1 cells 804:808 vascular cambium zone cells 782:808 vascular cambium zone cells where it is localized in the Golgi apparatus 782:853 Among the DUF579 family members, PtrDUF579-1 is found to be specifically expressed in vascular cambium zone cells where it is localized in the Golgi apparatus. 24899403 3 22 located localized 524:532 arg2 proteins 498:505 the Populus DUF579 family proteins 472:505 the Populus DUF579 family proteins 472:505 In this study, the Populus DUF579 family proteins were found to be localized in different cell types and subcellular locations. 24899403 3 22 located localized 524:532 arg1 types 552:556 different cell types 537:556 different cell types 537:556 In this study, the Populus DUF579 family proteins were found to be localized in different cell types and subcellular locations. 24899403 3 22 located localized 524:532 arg1 locations 574:582 subcellular locations 562:582 subcellular locations 562:582 In this study, the Populus DUF579 family proteins were found to be localized in different cell types and subcellular locations. 24899403 4 23 theme proteins 624:631 arg1 patterns 608:615 The diverse expression patterns 585:615 The diverse expression patterns of the proteins 585:631 The diverse expression patterns of the proteins indicate that they may perform different functions in Populus. 24899403 8 24 theme cell 1169:1172 arg1 wall 1174:1177 the cambium cell wall 1157:1177 the cambium cell wall 1157:1177 Cell walls analysis showed that the composition of the pectin fraction of the cambium cell wall was altered while other polysaccharides were not affected in PtrDUF579-1 suppressed plants. 24899403 8 25 theme cambium 1161:1167 arg1 wall 1174:1177 the cambium cell wall 1157:1177 the cambium cell wall 1157:1177 Cell walls analysis showed that the composition of the pectin fraction of the cambium cell wall was altered while other polysaccharides were not affected in PtrDUF579-1 suppressed plants. 24899403 7 26 theme suppressed 1064:1073 arg1 plants 1075:1080 PtrDUF579-1 suppressed plants 1052:1080 PtrDUF579-1 suppressed plants 1052:1080 Cambium cell division and xylem tissue growth was inhibited while secondary cell wall formation was unchanged in PtrDUF579-1 suppressed plants. 24899403 9 27 dep suggest 1288:1294 arg1 involved 1367:1374 involved 1367:1374 be involved in cambium cell proliferation in Populus 1364:1415 This observation suggest cambium expressed PtrDUF579-1 may affect cell wall biosynthesis and be involved in cambium cell proliferation in Populus. 24899403 9 27 dep suggest 1288:1294 arg1 affect 1330:1335 affect 1330:1335 may affect cell wall biosynthesis 1326:1358 This observation suggest cambium expressed PtrDUF579-1 may affect cell wall biosynthesis and be involved in cambium cell proliferation in Populus. 24899403 5 28 located localized 822:830 arg1 apparatus 845:853 the Golgi apparatus 835:853 the Golgi apparatus 835:853 Among the DUF579 family members, PtrDUF579-1 is found to be specifically expressed in vascular cambium zone cells where it is localized in the Golgi apparatus. 24899403 5 28 located localized 822:830 arg2 it 816:817 it 816:817 it 816:817 Among the DUF579 family members, PtrDUF579-1 is found to be specifically expressed in vascular cambium zone cells where it is localized in the Golgi apparatus. 24899403 8 29 theme walls 1088:1092 arg1 analysis 1094:1101 Cell walls analysis 1083:1101 Cell walls analysis 1083:1101 Cell walls analysis showed that the composition of the pectin fraction of the cambium cell wall was altered while other polysaccharides were not affected in PtrDUF579-1 suppressed plants. 24899403 1 30 theme family 171:176 arg1 proteins 178:185 DUF579 (domain of unknown function 579) family proteins 131:185 DUF579 (domain of unknown function 579) family proteins 131:185 DUF579 (domain of unknown function 579) family proteins contain a DUF579 domain structure but vary greatly in their overall sequence similarity. 24899403 0 31 theme Diverse 0:6 arg1 roles 8:12 Diverse roles 0:12 Diverse roles of PtrDUF579 proteins in Populus and PtrDUF579-1 0:61 Diverse roles of PtrDUF579 proteins in Populus and PtrDUF579-1 function in vascular cambium proliferation during secondary growth. 24899403 9 32 theme cell 1337:1340 arg1 biosynthesis 1347:1358 cell wall biosynthesis 1337:1358 cell wall biosynthesis 1337:1358 This observation suggest cambium expressed PtrDUF579-1 may affect cell wall biosynthesis and be involved in cambium cell proliferation in Populus. 24899403 10 33 theme diverse 1457:1463 arg1 set 1465:1467 a diverse set 1455:1467 a diverse set of roles 1455:1476 Overall, DUF579 family proteins play a diverse set of roles in Populus. 24899403 10 33 theme diverse 1457:1463 arg1 roles 1472:1476 roles 1472:1476 roles 1472:1476 Overall, DUF579 family proteins play a diverse set of roles in Populus. 24899403 2 34 from biosynthesis 344:355 arg1 Arabidopsis 360:370 Arabidopsis 360:370 Arabidopsis 360:370 Several DUF579 proteins have been found to play a role in cell wall biosynthesis in Arabidopsis, while DUF579 family genes have not yet been systematically investigated in Populus. 24899403 3 35 theme different 537:545 arg1 types 552:556 different cell types 537:556 different cell types 537:556 In this study, the Populus DUF579 family proteins were found to be localized in different cell types and subcellular locations. 24899403 4 36 theme different 664:672 arg1 functions 674:682 different functions 664:682 different functions 664:682 The diverse expression patterns of the proteins indicate that they may perform different functions in Populus. 24899403 0 37 theme PtrDUF579 17:25 arg1 proteins 27:34 PtrDUF579 proteins 17:34 PtrDUF579 proteins 17:34 Diverse roles of PtrDUF579 proteins in Populus and PtrDUF579-1 function in vascular cambium proliferation during secondary growth. 24899403 7 38 from plants 1075:1080 arg1 unchanged 1039:1047 unchanged 1039:1047 unchanged 1039:1047 Cambium cell division and xylem tissue growth was inhibited while secondary cell wall formation was unchanged in PtrDUF579-1 suppressed plants. 24899403 3 39 located found 512:516 arg1 study 465:469 this study 460:469 this study 460:469 In this study, the Populus DUF579 family proteins were found to be localized in different cell types and subcellular locations. 24899403 3 39 located found 512:516 arg2 proteins 498:505 the Populus DUF579 family proteins 472:505 the Populus DUF579 family proteins 472:505 In this study, the Populus DUF579 family proteins were found to be localized in different cell types and subcellular locations. 24899403 8 40 theme suppressed 1252:1261 arg1 plants 1263:1268 PtrDUF579-1 suppressed plants 1240:1268 PtrDUF579-1 suppressed plants 1240:1268 Cell walls analysis showed that the composition of the pectin fraction of the cambium cell wall was altered while other polysaccharides were not affected in PtrDUF579-1 suppressed plants. 24899403 5 41 theme zone 799:802 arg1 cells 804:808 vascular cambium zone cells 782:808 vascular cambium zone cells where it is localized in the Golgi apparatus 782:853 Among the DUF579 family members, PtrDUF579-1 is found to be specifically expressed in vascular cambium zone cells where it is localized in the Golgi apparatus. 24899403 7 42 theme PtrDUF579-1 1052:1062 arg1 plants 1075:1080 PtrDUF579-1 suppressed plants 1052:1080 PtrDUF579-1 suppressed plants 1052:1080 Cambium cell division and xylem tissue growth was inhibited while secondary cell wall formation was unchanged in PtrDUF579-1 suppressed plants. 24899403 3 43 theme Populus 476:482 arg1 proteins 498:505 the Populus DUF579 family proteins 472:505 the Populus DUF579 family proteins 472:505 In this study, the Populus DUF579 family proteins were found to be localized in different cell types and subcellular locations. 24899403 4 44 theme expression 597:606 arg1 patterns 608:615 The diverse expression patterns 585:615 The diverse expression patterns of the proteins 585:631 The diverse expression patterns of the proteins indicate that they may perform different functions in Populus. 24899403 8 45 theme Cell 1083:1086 arg1 walls 1088:1092 Cell walls 1083:1092 Cell walls analysis 1083:1101 Cell walls analysis showed that the composition of the pectin fraction of the cambium cell wall was altered while other polysaccharides were not affected in PtrDUF579-1 suppressed plants. 24899403 1 46 theme DUF579 197:202 arg1 structure 211:219 a DUF579 domain structure 195:219 a DUF579 domain structure 195:219 DUF579 (domain of unknown function 579) family proteins contain a DUF579 domain structure but vary greatly in their overall sequence similarity. 24899403 5 47 theme Golgi 839:843 arg1 apparatus 845:853 the Golgi apparatus 835:853 the Golgi apparatus 835:853 Among the DUF579 family members, PtrDUF579-1 is found to be specifically expressed in vascular cambium zone cells where it is localized in the Golgi apparatus. 24899403 2 48 theme family 386:391 arg1 genes 393:397 DUF579 family genes 379:397 DUF579 family genes 379:397 Several DUF579 proteins have been found to play a role in cell wall biosynthesis in Arabidopsis, while DUF579 family genes have not yet been systematically investigated in Populus. 24899403 0 49 theme proteins 27:34 arg1 roles 8:12 Diverse roles 0:12 Diverse roles of PtrDUF579 proteins in Populus and PtrDUF579-1 0:61 Diverse roles of PtrDUF579 proteins in Populus and PtrDUF579-1 function in vascular cambium proliferation during secondary growth. 24899403 6 50 theme diameter 924:931 arg1 size 933:936 stem diameter size 919:936 stem diameter size 919:936 Suppression of PtrDUF579-1 expression reduced plant height and stem diameter size. 24899403 3 51 theme subcellular 562:572 arg1 locations 574:582 subcellular locations 562:582 subcellular locations 562:582 In this study, the Populus DUF579 family proteins were found to be localized in different cell types and subcellular locations. 24899403 1 52 theme domain 204:209 arg1 structure 211:219 a DUF579 domain structure 195:219 a DUF579 domain structure 195:219 DUF579 (domain of unknown function 579) family proteins contain a DUF579 domain structure but vary greatly in their overall sequence similarity. 24899403 6 53 theme stem 919:922 arg1 size 933:936 stem diameter size 919:936 stem diameter size 919:936 Suppression of PtrDUF579-1 expression reduced plant height and stem diameter size. 24899403 7 54 theme wall 1020:1023 arg1 formation 1025:1033 secondary cell wall formation 1005:1033 secondary cell wall formation 1005:1033 Cambium cell division and xylem tissue growth was inhibited while secondary cell wall formation was unchanged in PtrDUF579-1 suppressed plants. 24899403 9 55 theme wall 1342:1345 arg1 biosynthesis 1347:1358 cell wall biosynthesis 1337:1358 cell wall biosynthesis 1337:1358 This observation suggest cambium expressed PtrDUF579-1 may affect cell wall biosynthesis and be involved in cambium cell proliferation in Populus. 24899403 3 56 theme cell 547:550 arg1 types 552:556 different cell types 537:556 different cell types 537:556 In this study, the Populus DUF579 family proteins were found to be localized in different cell types and subcellular locations. 24899403 8 57 theme other 1197:1201 arg1 polysaccharides 1203:1217 other polysaccharides 1197:1217 other polysaccharides 1197:1217 Cell walls analysis showed that the composition of the pectin fraction of the cambium cell wall was altered while other polysaccharides were not affected in PtrDUF579-1 suppressed plants. 24899403 6 58 theme plant 902:906 arg1 height 908:913 plant height 902:913 plant height 902:913 Suppression of PtrDUF579-1 expression reduced plant height and stem diameter size. 24899403 6 59 theme expression 883:892 arg1 Suppression 856:866 Suppression 856:866 Suppression of PtrDUF579-1 expression 856:892 Suppression of PtrDUF579-1 expression reduced plant height and stem diameter size. 24899403 5 60 theme cambium 791:797 arg1 cells 804:808 vascular cambium zone cells 782:808 vascular cambium zone cells where it is localized in the Golgi apparatus 782:853 Among the DUF579 family members, PtrDUF579-1 is found to be specifically expressed in vascular cambium zone cells where it is localized in the Golgi apparatus. 24899403 9 61 theme cambium 1379:1385 arg1 proliferation 1392:1404 cambium cell proliferation 1379:1404 cambium cell proliferation 1379:1404 This observation suggest cambium expressed PtrDUF579-1 may affect cell wall biosynthesis and be involved in cambium cell proliferation in Populus. 24899403 7 62 theme secondary 1005:1013 arg1 formation 1025:1033 secondary cell wall formation 1005:1033 secondary cell wall formation 1005:1033 Cambium cell division and xylem tissue growth was inhibited while secondary cell wall formation was unchanged in PtrDUF579-1 suppressed plants. 24899403 1 63 theme DUF579 131:136 arg1 proteins 178:185 DUF579 (domain of unknown function 579) family proteins 131:185 DUF579 (domain of unknown function 579) family proteins 131:185 DUF579 (domain of unknown function 579) family proteins contain a DUF579 domain structure but vary greatly in their overall sequence similarity. 24899403 9 64 theme cell 1387:1390 arg1 proliferation 1392:1404 cambium cell proliferation 1379:1404 cambium cell proliferation 1379:1404 This observation suggest cambium expressed PtrDUF579-1 may affect cell wall biosynthesis and be involved in cambium cell proliferation in Populus. 24899403 5 65 theme family 713:718 arg1 members 720:726 the DUF579 family members 702:726 the DUF579 family members 702:726 Among the DUF579 family members, PtrDUF579-1 is found to be specifically expressed in vascular cambium zone cells where it is localized in the Golgi apparatus. 24899403 7 66 theme cell 1015:1018 arg1 formation 1025:1033 secondary cell wall formation 1005:1033 secondary cell wall formation 1005:1033 Cambium cell division and xylem tissue growth was inhibited while secondary cell wall formation was unchanged in PtrDUF579-1 suppressed plants. 24899403 1 67 dep DUF579 131:136 arg1 domain 139:144 domain 139:144 domain of unknown function 579 139:168 DUF579 (domain of unknown function 579) family proteins contain a DUF579 domain structure but vary greatly in their overall sequence similarity. 24899403 1 67 dep DUF579 131:136 arg1 function 157:164 unknown function 579 149:168 unknown function 579 149:168 DUF579 (domain of unknown function 579) family proteins contain a DUF579 domain structure but vary greatly in their overall sequence similarity. 24899403 7 68 theme xylem 965:969 arg1 growth 978:983 xylem tissue growth 965:983 xylem tissue growth 965:983 Cambium cell division and xylem tissue growth was inhibited while secondary cell wall formation was unchanged in PtrDUF579-1 suppressed plants. 24899403 3 69 theme family 491:496 arg1 proteins 498:505 the Populus DUF579 family proteins 472:505 the Populus DUF579 family proteins 472:505 In this study, the Populus DUF579 family proteins were found to be localized in different cell types and subcellular locations. 24899403 1 70 contain contain 187:193 arg2 structure 211:219 a DUF579 domain structure 195:219 a DUF579 domain structure 195:219 DUF579 (domain of unknown function 579) family proteins contain a DUF579 domain structure but vary greatly in their overall sequence similarity. 24899403 1 70 contain contain 187:193 arg1 proteins 178:185 DUF579 (domain of unknown function 579) family proteins 131:185 DUF579 (domain of unknown function 579) family proteins 131:185 DUF579 (domain of unknown function 579) family proteins contain a DUF579 domain structure but vary greatly in their overall sequence similarity. 24899403 7 71 theme tissue 971:976 arg1 growth 978:983 xylem tissue growth 965:983 xylem tissue growth 965:983 Cambium cell division and xylem tissue growth was inhibited while secondary cell wall formation was unchanged in PtrDUF579-1 suppressed plants. 24899403 3 72 theme DUF579 484:489 arg1 proteins 498:505 the Populus DUF579 family proteins 472:505 the Populus DUF579 family proteins 472:505 In this study, the Populus DUF579 family proteins were found to be localized in different cell types and subcellular locations. 24899403 4 73 theme diverse 589:595 arg1 patterns 608:615 The diverse expression patterns 585:615 The diverse expression patterns of the proteins 585:631 The diverse expression patterns of the proteins indicate that they may perform different functions in Populus. 24899403 1 74 theme unknown 149:155 arg1 function 157:164 unknown function 579 149:168 unknown function 579 149:168 DUF579 (domain of unknown function 579) family proteins contain a DUF579 domain structure but vary greatly in their overall sequence similarity. 24899403 8 75 theme wall 1174:1177 arg1 fraction 1145:1152 the pectin fraction 1134:1152 the pectin fraction of the cambium cell wall 1134:1177 Cell walls analysis showed that the composition of the pectin fraction of the cambium cell wall was altered while other polysaccharides were not affected in PtrDUF579-1 suppressed plants. 24899403 2 76 theme wall 339:342 arg1 biosynthesis 344:355 cell wall biosynthesis 334:355 cell wall biosynthesis in Arabidopsis 334:370 Several DUF579 proteins have been found to play a role in cell wall biosynthesis in Arabidopsis, while DUF579 family genes have not yet been systematically investigated in Populus. 24899403 8 77 theme pectin 1138:1143 arg1 fraction 1145:1152 the pectin fraction 1134:1152 the pectin fraction of the cambium cell wall 1134:1177 Cell walls analysis showed that the composition of the pectin fraction of the cambium cell wall was altered while other polysaccharides were not affected in PtrDUF579-1 suppressed plants. 24657421 7 0 theme spectra 1227:1233 arg1 analysis 1181:1188 Principal component analysis 1161:1188 Principal component analysis of the second derivative transformed spectra 1161:1233 Principal component analysis of the second derivative transformed spectra confirmed that fatty acids of the cell membranes, amides of proteins and polysaccharides of the cell wall had the major contribution to data variation. 24657421 0 1 from evaluation 19:28 arg1 composition 69:79 the cellular biochemical composition 44:79 the cellular biochemical composition of the phytopathogenic fungus Alternaria alternata induced by extracts of some Greek medicinal and aromatic plants 44:194 FTIR spectroscopic evaluation of changes in the cellular biochemical composition of the phytopathogenic fungus Alternaria alternata induced by extracts of some Greek medicinal and aromatic plants. 24657421 0 2 theme plants 189:194 arg1 extracts 143:150 extracts 143:150 extracts of some Greek medicinal and aromatic plants 143:194 FTIR spectroscopic evaluation of changes in the cellular biochemical composition of the phytopathogenic fungus Alternaria alternata induced by extracts of some Greek medicinal and aromatic plants. 24657421 2 3 theme Lamiaceae 373:381 arg1 L. 413:414 L. 413:414 L. 413:414 Lamiaceae species (Hyssopus officinalis L., Melissa officinalis L., Origanum dictamnus L., Origanum vulgare L. and Salvia officinalis L.) were found to enhance significantly the mycelium growth whereas Crocus sativus appears to inhibit it slightly. 24657421 2 3 theme Lamiaceae 373:381 arg1 Origanum 441:448 Origanum 441:448 Origanum 441:448 Lamiaceae species (Hyssopus officinalis L., Melissa officinalis L., Origanum dictamnus L., Origanum vulgare L. and Salvia officinalis L.) were found to enhance significantly the mycelium growth whereas Crocus sativus appears to inhibit it slightly. 24657421 2 3 theme Lamiaceae 373:381 arg1 species 383:389 Lamiaceae species 373:389 Lamiaceae species (Hyssopus officinalis L., Melissa officinalis L., Origanum dictamnus L., Origanum vulgare L. and Salvia officinalis L.) 373:509 Lamiaceae species (Hyssopus officinalis L., Melissa officinalis L., Origanum dictamnus L., Origanum vulgare L. and Salvia officinalis L.) were found to enhance significantly the mycelium growth whereas Crocus sativus appears to inhibit it slightly. 24657421 2 3 theme Lamiaceae 373:381 arg1 L. 507:508 L. 507:508 L. 507:508 Lamiaceae species (Hyssopus officinalis L., Melissa officinalis L., Origanum dictamnus L., Origanum vulgare L. and Salvia officinalis L.) were found to enhance significantly the mycelium growth whereas Crocus sativus appears to inhibit it slightly. 24657421 2 3 theme Lamiaceae 373:381 arg1 L. 437:438 L. 437:438 L. 437:438 Lamiaceae species (Hyssopus officinalis L., Melissa officinalis L., Origanum dictamnus L., Origanum vulgare L. and Salvia officinalis L.) were found to enhance significantly the mycelium growth whereas Crocus sativus appears to inhibit it slightly. 24657421 2 3 theme Lamiaceae 373:381 arg1 L. 481:482 L. 481:482 L. 481:482 Lamiaceae species (Hyssopus officinalis L., Melissa officinalis L., Origanum dictamnus L., Origanum vulgare L. and Salvia officinalis L.) were found to enhance significantly the mycelium growth whereas Crocus sativus appears to inhibit it slightly. 24657421 1 4 theme extracts 247:254 arg1 activity 227:234 the biological activity 212:234 the biological activity of aquatic extracts of selected Greek medicinal and aromatic plants to the phytopathogenic fungus Alternaria alternata 212:353 In this study, the biological activity of aquatic extracts of selected Greek medicinal and aromatic plants to the phytopathogenic fungus Alternaria alternata was investigated. 24657421 0 5 theme aromatic 180:187 arg1 plants 189:194 some Greek medicinal and aromatic plants 155:194 some Greek medicinal and aromatic plants 155:194 FTIR spectroscopic evaluation of changes in the cellular biochemical composition of the phytopathogenic fungus Alternaria alternata induced by extracts of some Greek medicinal and aromatic plants. 24657421 0 6 theme fungus 104:109 arg1 alternata 122:130 the phytopathogenic fungus Alternaria alternata 84:130 the phytopathogenic fungus Alternaria alternata induced by extracts of some Greek medicinal and aromatic plants 84:194 FTIR spectroscopic evaluation of changes in the cellular biochemical composition of the phytopathogenic fungus Alternaria alternata induced by extracts of some Greek medicinal and aromatic plants. 24657421 7 7 theme data 1371:1374 arg1 variation 1376:1384 data variation 1371:1384 data variation 1371:1384 Principal component analysis of the second derivative transformed spectra confirmed that fatty acids of the cell membranes, amides of proteins and polysaccharides of the cell wall had the major contribution to data variation. 24657421 1 8 theme selected 259:266 arg1 plants 297:302 selected Greek medicinal and aromatic plants 259:302 selected Greek medicinal and aromatic plants to the phytopathogenic fungus Alternaria alternata 259:353 In this study, the biological activity of aquatic extracts of selected Greek medicinal and aromatic plants to the phytopathogenic fungus Alternaria alternata was investigated. 24657421 0 9 theme phytopathogenic 88:102 arg1 alternata 122:130 the phytopathogenic fungus Alternaria alternata 84:130 the phytopathogenic fungus Alternaria alternata induced by extracts of some Greek medicinal and aromatic plants 84:194 FTIR spectroscopic evaluation of changes in the cellular biochemical composition of the phytopathogenic fungus Alternaria alternata induced by extracts of some Greek medicinal and aromatic plants. 24657421 3 10 theme conidia 717:723 arg1 % 740:740 +65% 737:740 +65% 737:740 M. officinalis and S. officinalis caused the highest stimulation in mycelium growth (+97%) and conidia production (+65%) respectively. 24657421 3 10 theme conidia 717:723 arg1 production 725:734 conidia production 717:734 conidia production (+65%) 717:741 M. officinalis and S. officinalis caused the highest stimulation in mycelium growth (+97%) and conidia production (+65%) respectively. 24657421 1 11 theme Greek 268:272 arg1 plants 297:302 selected Greek medicinal and aromatic plants 259:302 selected Greek medicinal and aromatic plants to the phytopathogenic fungus Alternaria alternata 259:353 In this study, the biological activity of aquatic extracts of selected Greek medicinal and aromatic plants to the phytopathogenic fungus Alternaria alternata was investigated. 24657421 0 12 theme alternata 122:130 arg1 composition 69:79 the cellular biochemical composition 44:79 the cellular biochemical composition of the phytopathogenic fungus Alternaria alternata induced by extracts of some Greek medicinal and aromatic plants 44:194 FTIR spectroscopic evaluation of changes in the cellular biochemical composition of the phytopathogenic fungus Alternaria alternata induced by extracts of some Greek medicinal and aromatic plants. 24657421 7 13 theme wall 1336:1339 arg1 polysaccharides 1308:1322 polysaccharides 1308:1322 polysaccharides of the cell wall 1308:1339 Principal component analysis of the second derivative transformed spectra confirmed that fatty acids of the cell membranes, amides of proteins and polysaccharides of the cell wall had the major contribution to data variation. 24657421 7 13 theme wall 1336:1339 arg1 acids 1256:1260 fatty acids 1250:1260 fatty acids of the cell membranes 1250:1282 Principal component analysis of the second derivative transformed spectra confirmed that fatty acids of the cell membranes, amides of proteins and polysaccharides of the cell wall had the major contribution to data variation. 24657421 7 13 theme wall 1336:1339 arg1 amides 1285:1290 amides 1285:1290 amides of proteins 1285:1302 Principal component analysis of the second derivative transformed spectra confirmed that fatty acids of the cell membranes, amides of proteins and polysaccharides of the cell wall had the major contribution to data variation. 24657421 0 14 theme Alternaria 111:120 arg1 alternata 122:130 the phytopathogenic fungus Alternaria alternata 84:130 the phytopathogenic fungus Alternaria alternata induced by extracts of some Greek medicinal and aromatic plants 84:194 FTIR spectroscopic evaluation of changes in the cellular biochemical composition of the phytopathogenic fungus Alternaria alternata induced by extracts of some Greek medicinal and aromatic plants. 24657421 2 15 dep Origanum 441:448 arg1 L. 460:461 Origanum dictamnus L. 441:461 Origanum dictamnus L. 441:461 Lamiaceae species (Hyssopus officinalis L., Melissa officinalis L., Origanum dictamnus L., Origanum vulgare L. and Salvia officinalis L.) were found to enhance significantly the mycelium growth whereas Crocus sativus appears to inhibit it slightly. 24657421 6 16 from changes 1033:1039 arg1 regions 1053:1059 spectral regions 1044:1059 spectral regions corresponding to absorptions of the major cellular constituents such as cell membrane and proteins 1044:1158 The second derivative transformation of spectra revealed changes in spectral regions corresponding to absorptions of the major cellular constituents such as cell membrane and proteins. 24657421 2 17 dep species 383:389 arg1 L. 413:414 L. 413:414 L. 413:414 Lamiaceae species (Hyssopus officinalis L., Melissa officinalis L., Origanum dictamnus L., Origanum vulgare L. and Salvia officinalis L.) were found to enhance significantly the mycelium growth whereas Crocus sativus appears to inhibit it slightly. 24657421 2 17 dep species 383:389 arg1 Origanum 441:448 Origanum 441:448 Origanum 441:448 Lamiaceae species (Hyssopus officinalis L., Melissa officinalis L., Origanum dictamnus L., Origanum vulgare L. and Salvia officinalis L.) were found to enhance significantly the mycelium growth whereas Crocus sativus appears to inhibit it slightly. 24657421 2 17 dep species 383:389 arg1 species 383:389 Lamiaceae species 373:389 Lamiaceae species (Hyssopus officinalis L., Melissa officinalis L., Origanum dictamnus L., Origanum vulgare L. and Salvia officinalis L.) 373:509 Lamiaceae species (Hyssopus officinalis L., Melissa officinalis L., Origanum dictamnus L., Origanum vulgare L. and Salvia officinalis L.) were found to enhance significantly the mycelium growth whereas Crocus sativus appears to inhibit it slightly. 24657421 2 17 dep species 383:389 arg1 L. 507:508 L. 507:508 L. 507:508 Lamiaceae species (Hyssopus officinalis L., Melissa officinalis L., Origanum dictamnus L., Origanum vulgare L. and Salvia officinalis L.) were found to enhance significantly the mycelium growth whereas Crocus sativus appears to inhibit it slightly. 24657421 2 17 dep species 383:389 arg1 L. 437:438 L. 437:438 L. 437:438 Lamiaceae species (Hyssopus officinalis L., Melissa officinalis L., Origanum dictamnus L., Origanum vulgare L. and Salvia officinalis L.) were found to enhance significantly the mycelium growth whereas Crocus sativus appears to inhibit it slightly. 24657421 2 17 dep species 383:389 arg1 L. 481:482 L. 481:482 L. 481:482 Lamiaceae species (Hyssopus officinalis L., Melissa officinalis L., Origanum dictamnus L., Origanum vulgare L. and Salvia officinalis L.) were found to enhance significantly the mycelium growth whereas Crocus sativus appears to inhibit it slightly. 24657421 0 18 theme spectroscopic 5:17 arg1 evaluation 19:28 FTIR spectroscopic evaluation 0:28 FTIR spectroscopic evaluation of changes in the cellular biochemical composition of the phytopathogenic fungus Alternaria alternata induced by extracts of some Greek medicinal and aromatic plants. 0:195 FTIR spectroscopic evaluation of changes in the cellular biochemical composition of the phytopathogenic fungus Alternaria alternata induced by extracts of some Greek medicinal and aromatic plants. 24657421 0 19 from changes 33:39 arg1 composition 69:79 the cellular biochemical composition 44:79 the cellular biochemical composition of the phytopathogenic fungus Alternaria alternata induced by extracts of some Greek medicinal and aromatic plants 44:194 FTIR spectroscopic evaluation of changes in the cellular biochemical composition of the phytopathogenic fungus Alternaria alternata induced by extracts of some Greek medicinal and aromatic plants. 24657421 7 20 theme cell 1269:1272 arg1 membranes 1274:1282 the cell membranes 1265:1282 the cell membranes 1265:1282 Principal component analysis of the second derivative transformed spectra confirmed that fatty acids of the cell membranes, amides of proteins and polysaccharides of the cell wall had the major contribution to data variation. 24657421 5 21 theme original 915:922 arg1 spectra 924:930 original spectra 915:930 original spectra 915:930 Differences of original spectra were assigned mainly to amides of proteins. 24657421 0 22 theme FTIR 0:3 arg1 evaluation 19:28 FTIR spectroscopic evaluation 0:28 FTIR spectroscopic evaluation of changes in the cellular biochemical composition of the phytopathogenic fungus Alternaria alternata induced by extracts of some Greek medicinal and aromatic plants. 0:195 FTIR spectroscopic evaluation of changes in the cellular biochemical composition of the phytopathogenic fungus Alternaria alternata induced by extracts of some Greek medicinal and aromatic plants. 24657421 1 23 theme medicinal 274:282 arg1 plants 297:302 selected Greek medicinal and aromatic plants 259:302 selected Greek medicinal and aromatic plants to the phytopathogenic fungus Alternaria alternata 259:353 In this study, the biological activity of aquatic extracts of selected Greek medicinal and aromatic plants to the phytopathogenic fungus Alternaria alternata was investigated. 24657421 5 24 theme spectra 924:930 arg1 Differences 900:910 Differences 900:910 Differences of original spectra 900:930 Differences of original spectra were assigned mainly to amides of proteins. 24657421 6 25 theme second 980:985 arg1 transformation 998:1011 The second derivative transformation 976:1011 The second derivative transformation of spectra 976:1022 The second derivative transformation of spectra revealed changes in spectral regions corresponding to absorptions of the major cellular constituents such as cell membrane and proteins. 24657421 7 26 theme cell 1331:1334 arg1 wall 1336:1339 the cell wall 1327:1339 the cell wall 1327:1339 Principal component analysis of the second derivative transformed spectra confirmed that fatty acids of the cell membranes, amides of proteins and polysaccharides of the cell wall had the major contribution to data variation. 24657421 7 27 theme Principal 1161:1169 arg1 analysis 1181:1188 Principal component analysis 1161:1188 Principal component analysis of the second derivative transformed spectra 1161:1233 Principal component analysis of the second derivative transformed spectra confirmed that fatty acids of the cell membranes, amides of proteins and polysaccharides of the cell wall had the major contribution to data variation. 24657421 7 28 theme major 1349:1353 arg1 contribution 1355:1366 the major contribution 1345:1366 the major contribution to data variation 1345:1384 Principal component analysis of the second derivative transformed spectra confirmed that fatty acids of the cell membranes, amides of proteins and polysaccharides of the cell wall had the major contribution to data variation. 24657421 8 29 theme FTIR 1387:1390 arg1 ratios 1402:1407 FTIR band area ratios 1387:1407 FTIR band area ratios 1387:1407 FTIR band area ratios were found to correlate with fungal mycelium growth. 24657421 6 30 theme spectral 1044:1051 arg1 regions 1053:1059 spectral regions 1044:1059 spectral regions corresponding to absorptions of the major cellular constituents such as cell membrane and proteins 1044:1158 The second derivative transformation of spectra revealed changes in spectral regions corresponding to absorptions of the major cellular constituents such as cell membrane and proteins. 24657421 7 31 theme component 1171:1179 arg1 analysis 1181:1188 Principal component analysis 1161:1188 Principal component analysis of the second derivative transformed spectra 1161:1233 Principal component analysis of the second derivative transformed spectra confirmed that fatty acids of the cell membranes, amides of proteins and polysaccharides of the cell wall had the major contribution to data variation. 24657421 1 32 theme aromatic 288:295 arg1 plants 297:302 selected Greek medicinal and aromatic plants 259:302 selected Greek medicinal and aromatic plants to the phytopathogenic fungus Alternaria alternata 259:353 In this study, the biological activity of aquatic extracts of selected Greek medicinal and aromatic plants to the phytopathogenic fungus Alternaria alternata was investigated. 24657421 2 33 theme mycelium 551:558 arg1 growth 560:565 the mycelium growth 547:565 the mycelium growth 547:565 Lamiaceae species (Hyssopus officinalis L., Melissa officinalis L., Origanum dictamnus L., Origanum vulgare L. and Salvia officinalis L.) were found to enhance significantly the mycelium growth whereas Crocus sativus appears to inhibit it slightly. 24657421 8 34 theme mycelium 1445:1452 arg1 growth 1454:1459 fungal mycelium growth 1438:1459 fungal mycelium growth 1438:1459 FTIR band area ratios were found to correlate with fungal mycelium growth. 24657421 1 35 theme plants 297:302 arg1 extracts 247:254 aquatic extracts 239:254 aquatic extracts of selected Greek medicinal and aromatic plants to the phytopathogenic fungus Alternaria alternata 239:353 In this study, the biological activity of aquatic extracts of selected Greek medicinal and aromatic plants to the phytopathogenic fungus Alternaria alternata was investigated. 24657421 8 36 theme fungal 1438:1443 arg1 growth 1454:1459 fungal mycelium growth 1438:1459 fungal mycelium growth 1438:1459 FTIR band area ratios were found to correlate with fungal mycelium growth. 24657421 8 37 theme area 1397:1400 arg1 ratios 1402:1407 FTIR band area ratios 1387:1407 FTIR band area ratios 1387:1407 FTIR band area ratios were found to correlate with fungal mycelium growth. 24657421 7 38 theme proteins 1295:1302 arg1 polysaccharides 1308:1322 polysaccharides 1308:1322 polysaccharides of the cell wall 1308:1339 Principal component analysis of the second derivative transformed spectra confirmed that fatty acids of the cell membranes, amides of proteins and polysaccharides of the cell wall had the major contribution to data variation. 24657421 7 38 theme proteins 1295:1302 arg1 acids 1256:1260 fatty acids 1250:1260 fatty acids of the cell membranes 1250:1282 Principal component analysis of the second derivative transformed spectra confirmed that fatty acids of the cell membranes, amides of proteins and polysaccharides of the cell wall had the major contribution to data variation. 24657421 7 38 theme proteins 1295:1302 arg1 amides 1285:1290 amides 1285:1290 amides of proteins 1285:1302 Principal component analysis of the second derivative transformed spectra confirmed that fatty acids of the cell membranes, amides of proteins and polysaccharides of the cell wall had the major contribution to data variation. 24657421 0 39 theme changes 33:39 arg1 evaluation 19:28 FTIR spectroscopic evaluation 0:28 FTIR spectroscopic evaluation of changes in the cellular biochemical composition of the phytopathogenic fungus Alternaria alternata induced by extracts of some Greek medicinal and aromatic plants. 0:195 FTIR spectroscopic evaluation of changes in the cellular biochemical composition of the phytopathogenic fungus Alternaria alternata induced by extracts of some Greek medicinal and aromatic plants. 24657421 4 40 dep Fourier 852:858 arg1 Transform 860:868 Transform 860:868 Transform Infrared Spectroscopy (FTIR) 860:897 In order to further investigate the bioactivity of plant extracts to A. alternata, we employed Fourier Transform Infrared Spectroscopy (FTIR). 24657421 0 41 from composition 69:79 arg1 evaluation 19:28 FTIR spectroscopic evaluation 0:28 FTIR spectroscopic evaluation of changes in the cellular biochemical composition of the phytopathogenic fungus Alternaria alternata induced by extracts of some Greek medicinal and aromatic plants. 0:195 FTIR spectroscopic evaluation of changes in the cellular biochemical composition of the phytopathogenic fungus Alternaria alternata induced by extracts of some Greek medicinal and aromatic plants. 24657421 6 42 theme derivative 987:996 arg1 transformation 998:1011 The second derivative transformation 976:1011 The second derivative transformation of spectra 976:1022 The second derivative transformation of spectra revealed changes in spectral regions corresponding to absorptions of the major cellular constituents such as cell membrane and proteins. 24657421 7 43 theme second 1197:1202 arg1 spectra 1227:1233 the second derivative transformed spectra 1193:1233 the second derivative transformed spectra 1193:1233 Principal component analysis of the second derivative transformed spectra confirmed that fatty acids of the cell membranes, amides of proteins and polysaccharides of the cell wall had the major contribution to data variation. 24657421 0 44 theme cellular 48:55 arg1 composition 69:79 the cellular biochemical composition 44:79 the cellular biochemical composition of the phytopathogenic fungus Alternaria alternata induced by extracts of some Greek medicinal and aromatic plants 44:194 FTIR spectroscopic evaluation of changes in the cellular biochemical composition of the phytopathogenic fungus Alternaria alternata induced by extracts of some Greek medicinal and aromatic plants. 24657421 7 45 theme derivative 1204:1213 arg1 spectra 1227:1233 the second derivative transformed spectra 1193:1233 the second derivative transformed spectra 1193:1233 Principal component analysis of the second derivative transformed spectra confirmed that fatty acids of the cell membranes, amides of proteins and polysaccharides of the cell wall had the major contribution to data variation. 24657421 0 46 theme Greek 160:164 arg1 plants 189:194 some Greek medicinal and aromatic plants 155:194 some Greek medicinal and aromatic plants 155:194 FTIR spectroscopic evaluation of changes in the cellular biochemical composition of the phytopathogenic fungus Alternaria alternata induced by extracts of some Greek medicinal and aromatic plants. 24657421 7 47 theme fatty 1250:1254 arg1 acids 1256:1260 fatty acids 1250:1260 fatty acids of the cell membranes 1250:1282 Principal component analysis of the second derivative transformed spectra confirmed that fatty acids of the cell membranes, amides of proteins and polysaccharides of the cell wall had the major contribution to data variation. 24657421 4 48 theme extracts 814:821 arg1 bioactivity 793:803 the bioactivity 789:803 the bioactivity of plant extracts to A. alternata 789:837 In order to further investigate the bioactivity of plant extracts to A. alternata, we employed Fourier Transform Infrared Spectroscopy (FTIR). 24657421 6 49 theme cell 1133:1136 arg1 membrane 1138:1145 cell membrane 1133:1145 cell membrane 1133:1145 The second derivative transformation of spectra revealed changes in spectral regions corresponding to absorptions of the major cellular constituents such as cell membrane and proteins. 24657421 1 50 theme phytopathogenic 311:325 arg1 alternata 345:353 the phytopathogenic fungus Alternaria alternata 307:353 the phytopathogenic fungus Alternaria alternata 307:353 In this study, the biological activity of aquatic extracts of selected Greek medicinal and aromatic plants to the phytopathogenic fungus Alternaria alternata was investigated. 24657421 4 51 theme Infrared 870:877 arg1 FTIR 893:896 FTIR 893:896 FTIR 893:896 In order to further investigate the bioactivity of plant extracts to A. alternata, we employed Fourier Transform Infrared Spectroscopy (FTIR). 24657421 4 51 theme Infrared 870:877 arg1 Spectroscopy 879:890 Infrared Spectroscopy 870:890 Infrared Spectroscopy (FTIR) 870:897 In order to further investigate the bioactivity of plant extracts to A. alternata, we employed Fourier Transform Infrared Spectroscopy (FTIR). 24657421 4 52 theme plant 808:812 arg1 extracts 814:821 plant extracts 808:821 plant extracts 808:821 In order to further investigate the bioactivity of plant extracts to A. alternata, we employed Fourier Transform Infrared Spectroscopy (FTIR). 24657421 7 53 theme transformed 1215:1225 arg1 spectra 1227:1233 the second derivative transformed spectra 1193:1233 the second derivative transformed spectra 1193:1233 Principal component analysis of the second derivative transformed spectra confirmed that fatty acids of the cell membranes, amides of proteins and polysaccharides of the cell wall had the major contribution to data variation. 24657421 3 54 theme S. 641:642 arg1 officinalis 644:654 S. officinalis 641:654 S. officinalis 641:654 M. officinalis and S. officinalis caused the highest stimulation in mycelium growth (+97%) and conidia production (+65%) respectively. 24657421 1 55 theme fungus 327:332 arg1 alternata 345:353 the phytopathogenic fungus Alternaria alternata 307:353 the phytopathogenic fungus Alternaria alternata 307:353 In this study, the biological activity of aquatic extracts of selected Greek medicinal and aromatic plants to the phytopathogenic fungus Alternaria alternata was investigated. 24657421 2 56 theme Crocus 575:580 arg1 sativus 582:588 Crocus sativus 575:588 Crocus sativus 575:588 Lamiaceae species (Hyssopus officinalis L., Melissa officinalis L., Origanum dictamnus L., Origanum vulgare L. and Salvia officinalis L.) were found to enhance significantly the mycelium growth whereas Crocus sativus appears to inhibit it slightly. 24657421 3 57 theme mycelium 690:697 arg1 growth 699:704 mycelium growth 690:704 mycelium growth (+97%) 690:711 M. officinalis and S. officinalis caused the highest stimulation in mycelium growth (+97%) and conidia production (+65%) respectively. 24657421 3 57 theme mycelium 690:697 arg1 % 710:710 +97% 707:710 +97% 707:710 M. officinalis and S. officinalis caused the highest stimulation in mycelium growth (+97%) and conidia production (+65%) respectively. 24657421 5 58 theme proteins 966:973 arg1 amides 956:961 amides 956:961 amides of proteins 956:973 Differences of original spectra were assigned mainly to amides of proteins. 24657421 8 59 theme band 1392:1395 arg1 ratios 1402:1407 FTIR band area ratios 1387:1407 FTIR band area ratios 1387:1407 FTIR band area ratios were found to correlate with fungal mycelium growth. 24657421 7 60 theme membranes 1274:1282 arg1 polysaccharides 1308:1322 polysaccharides 1308:1322 polysaccharides of the cell wall 1308:1339 Principal component analysis of the second derivative transformed spectra confirmed that fatty acids of the cell membranes, amides of proteins and polysaccharides of the cell wall had the major contribution to data variation. 24657421 7 60 theme membranes 1274:1282 arg1 acids 1256:1260 fatty acids 1250:1260 fatty acids of the cell membranes 1250:1282 Principal component analysis of the second derivative transformed spectra confirmed that fatty acids of the cell membranes, amides of proteins and polysaccharides of the cell wall had the major contribution to data variation. 24657421 7 60 theme membranes 1274:1282 arg1 amides 1285:1290 amides 1285:1290 amides of proteins 1285:1302 Principal component analysis of the second derivative transformed spectra confirmed that fatty acids of the cell membranes, amides of proteins and polysaccharides of the cell wall had the major contribution to data variation. 24657421 1 61 theme biological 216:225 arg1 activity 227:234 the biological activity 212:234 the biological activity of aquatic extracts of selected Greek medicinal and aromatic plants to the phytopathogenic fungus Alternaria alternata 212:353 In this study, the biological activity of aquatic extracts of selected Greek medicinal and aromatic plants to the phytopathogenic fungus Alternaria alternata was investigated. 24657421 0 62 theme medicinal 166:174 arg1 plants 189:194 some Greek medicinal and aromatic plants 155:194 some Greek medicinal and aromatic plants 155:194 FTIR spectroscopic evaluation of changes in the cellular biochemical composition of the phytopathogenic fungus Alternaria alternata induced by extracts of some Greek medicinal and aromatic plants. 24657421 3 63 theme highest 667:673 arg1 stimulation 675:685 the highest stimulation 663:685 the highest stimulation 663:685 M. officinalis and S. officinalis caused the highest stimulation in mycelium growth (+97%) and conidia production (+65%) respectively. 24657421 7 64 contain had 1341:1343 arg1 polysaccharides 1308:1322 polysaccharides 1308:1322 polysaccharides of the cell wall 1308:1339 Principal component analysis of the second derivative transformed spectra confirmed that fatty acids of the cell membranes, amides of proteins and polysaccharides of the cell wall had the major contribution to data variation. 24657421 7 64 contain had 1341:1343 arg1 acids 1256:1260 fatty acids 1250:1260 fatty acids of the cell membranes 1250:1282 Principal component analysis of the second derivative transformed spectra confirmed that fatty acids of the cell membranes, amides of proteins and polysaccharides of the cell wall had the major contribution to data variation. 24657421 7 64 contain had 1341:1343 arg1 amides 1285:1290 amides 1285:1290 amides of proteins 1285:1302 Principal component analysis of the second derivative transformed spectra confirmed that fatty acids of the cell membranes, amides of proteins and polysaccharides of the cell wall had the major contribution to data variation. 24657421 7 64 contain had 1341:1343 arg2 contribution 1355:1366 the major contribution 1345:1366 the major contribution to data variation 1345:1384 Principal component analysis of the second derivative transformed spectra confirmed that fatty acids of the cell membranes, amides of proteins and polysaccharides of the cell wall had the major contribution to data variation. 24657421 6 65 theme constituents 1112:1123 arg1 absorptions 1078:1088 absorptions 1078:1088 absorptions of the major cellular constituents such as cell membrane and proteins 1078:1158 The second derivative transformation of spectra revealed changes in spectral regions corresponding to absorptions of the major cellular constituents such as cell membrane and proteins. 24657421 6 66 theme major 1097:1101 arg1 proteins 1151:1158 proteins 1151:1158 proteins 1151:1158 The second derivative transformation of spectra revealed changes in spectral regions corresponding to absorptions of the major cellular constituents such as cell membrane and proteins. 24657421 6 66 theme major 1097:1101 arg1 membrane 1138:1145 cell membrane 1133:1145 cell membrane 1133:1145 The second derivative transformation of spectra revealed changes in spectral regions corresponding to absorptions of the major cellular constituents such as cell membrane and proteins. 24657421 6 66 theme major 1097:1101 arg1 constituents 1112:1123 the major cellular constituents 1093:1123 the major cellular constituents such as cell membrane and proteins 1093:1158 The second derivative transformation of spectra revealed changes in spectral regions corresponding to absorptions of the major cellular constituents such as cell membrane and proteins. 24657421 6 67 theme cellular 1103:1110 arg1 proteins 1151:1158 proteins 1151:1158 proteins 1151:1158 The second derivative transformation of spectra revealed changes in spectral regions corresponding to absorptions of the major cellular constituents such as cell membrane and proteins. 24657421 6 67 theme cellular 1103:1110 arg1 membrane 1138:1145 cell membrane 1133:1145 cell membrane 1133:1145 The second derivative transformation of spectra revealed changes in spectral regions corresponding to absorptions of the major cellular constituents such as cell membrane and proteins. 24657421 6 67 theme cellular 1103:1110 arg1 constituents 1112:1123 the major cellular constituents 1093:1123 the major cellular constituents such as cell membrane and proteins 1093:1158 The second derivative transformation of spectra revealed changes in spectral regions corresponding to absorptions of the major cellular constituents such as cell membrane and proteins. 24657421 0 68 theme biochemical 57:67 arg1 composition 69:79 the cellular biochemical composition 44:79 the cellular biochemical composition of the phytopathogenic fungus Alternaria alternata induced by extracts of some Greek medicinal and aromatic plants 44:194 FTIR spectroscopic evaluation of changes in the cellular biochemical composition of the phytopathogenic fungus Alternaria alternata induced by extracts of some Greek medicinal and aromatic plants. 24657421 1 69 theme Alternaria 334:343 arg1 alternata 345:353 the phytopathogenic fungus Alternaria alternata 307:353 the phytopathogenic fungus Alternaria alternata 307:353 In this study, the biological activity of aquatic extracts of selected Greek medicinal and aromatic plants to the phytopathogenic fungus Alternaria alternata was investigated. 24657421 3 70 theme M. 622:623 arg1 officinalis 625:635 M. officinalis 622:635 M. officinalis 622:635 M. officinalis and S. officinalis caused the highest stimulation in mycelium growth (+97%) and conidia production (+65%) respectively. 24657421 6 71 theme spectra 1016:1022 arg1 transformation 998:1011 The second derivative transformation 976:1011 The second derivative transformation of spectra 976:1022 The second derivative transformation of spectra revealed changes in spectral regions corresponding to absorptions of the major cellular constituents such as cell membrane and proteins. 24657421 1 72 theme aquatic 239:245 arg1 extracts 247:254 aquatic extracts 239:254 aquatic extracts of selected Greek medicinal and aromatic plants to the phytopathogenic fungus Alternaria alternata 239:353 In this study, the biological activity of aquatic extracts of selected Greek medicinal and aromatic plants to the phytopathogenic fungus Alternaria alternata was investigated. 24629936 4 0 theme higher 822:827 arg1 value 834:838 a higher FRAP value 820:838 a higher FRAP value 820:838 Inhibition of DPPH was high in ethanol extracts (48.9%) compared to aqueous extracts (19.7%), whereas aqueous extracts showed a higher FRAP value compared to ethanol extracts (0.98 and 0.61mmolFe(II)/100g, respectively). 24629936 0 1 theme formulations 116:127 arg1 development 72:82 development 72:82 development of novel food products and food formulations 72:127 Evaluating belinjau (Gnetum gnemon L.) seed flour quality as a base for development of novel food products and food formulations. 24629936 7 2 theme belinjau 1306:1313 arg1 flour 1320:1324 belinjau seed flour 1306:1324 belinjau seed flour 1306:1324 As belinjau seed flour possesses a rich nutraceutical value, it has high potential to be used as a basic raw material to develop new low cost nutritious functional foods. 24629936 2 3 theme acids 446:450 arg1 acids 446:450 essential amino acids 430:450 essential amino acids 430:450 Seed flour was found to be rich in protein (19.0g/100g), crude fibre (8.66g/100g), carbohydrates (64.1%), total dietary fibre (14.5%) and encompassed adequate amounts of essential amino acids, fatty acids and minerals. 24629936 2 3 theme acids 446:450 arg1 acids 459:463 fatty acids 453:463 fatty acids 453:463 Seed flour was found to be rich in protein (19.0g/100g), crude fibre (8.66g/100g), carbohydrates (64.1%), total dietary fibre (14.5%) and encompassed adequate amounts of essential amino acids, fatty acids and minerals. 24629936 2 3 theme acids 446:450 arg1 amounts 419:425 adequate amounts 410:425 adequate amounts of essential amino acids, fatty acids and minerals 410:476 Seed flour was found to be rich in protein (19.0g/100g), crude fibre (8.66g/100g), carbohydrates (64.1%), total dietary fibre (14.5%) and encompassed adequate amounts of essential amino acids, fatty acids and minerals. 24629936 2 3 theme acids 446:450 arg1 minerals 469:476 minerals 469:476 minerals 469:476 Seed flour was found to be rich in protein (19.0g/100g), crude fibre (8.66g/100g), carbohydrates (64.1%), total dietary fibre (14.5%) and encompassed adequate amounts of essential amino acids, fatty acids and minerals. 24629936 7 4 theme nutraceutical 1343:1355 arg1 value 1357:1361 a rich nutraceutical value 1336:1361 a rich nutraceutical value 1336:1361 As belinjau seed flour possesses a rich nutraceutical value, it has high potential to be used as a basic raw material to develop new low cost nutritious functional foods. 24629936 4 5 dep extracts 860:867 arg1 /100g 893:897 0.61mmolFe(II)/100g 879:897 0.61mmolFe(II)/100g 879:897 Inhibition of DPPH was high in ethanol extracts (48.9%) compared to aqueous extracts (19.7%), whereas aqueous extracts showed a higher FRAP value compared to ethanol extracts (0.98 and 0.61mmolFe(II)/100g, respectively). 24629936 4 5 dep extracts 860:867 arg1 0.98 870:873 0.98 870:873 0.98 870:873 Inhibition of DPPH was high in ethanol extracts (48.9%) compared to aqueous extracts (19.7%), whereas aqueous extracts showed a higher FRAP value compared to ethanol extracts (0.98 and 0.61mmolFe(II)/100g, respectively). 24629936 2 6 from rich 287:290 arg1 19.0g/100g 304:313 19.0g/100g 304:313 19.0g/100g 304:313 Seed flour was found to be rich in protein (19.0g/100g), crude fibre (8.66g/100g), carbohydrates (64.1%), total dietary fibre (14.5%) and encompassed adequate amounts of essential amino acids, fatty acids and minerals. 24629936 2 6 from rich 287:290 arg1 protein 295:301 protein 295:301 protein (19.0g/100g) 295:314 Seed flour was found to be rich in protein (19.0g/100g), crude fibre (8.66g/100g), carbohydrates (64.1%), total dietary fibre (14.5%) and encompassed adequate amounts of essential amino acids, fatty acids and minerals. 24629936 2 6 from rich 287:290 arg1 carbohydrates 343:355 carbohydrates 343:355 carbohydrates (64.1%) 343:363 Seed flour was found to be rich in protein (19.0g/100g), crude fibre (8.66g/100g), carbohydrates (64.1%), total dietary fibre (14.5%) and encompassed adequate amounts of essential amino acids, fatty acids and minerals. 24629936 2 6 from rich 287:290 arg1 fibre 323:327 fibre 323:327 fibre 323:327 Seed flour was found to be rich in protein (19.0g/100g), crude fibre (8.66g/100g), carbohydrates (64.1%), total dietary fibre (14.5%) and encompassed adequate amounts of essential amino acids, fatty acids and minerals. 24629936 2 6 from rich 287:290 arg1 fibre 380:384 fibre 380:384 fibre 380:384 Seed flour was found to be rich in protein (19.0g/100g), crude fibre (8.66g/100g), carbohydrates (64.1%), total dietary fibre (14.5%) and encompassed adequate amounts of essential amino acids, fatty acids and minerals. 24629936 1 7 theme Belinjau 130:137 arg1 flour 163:167 Belinjau (Gnetum gnemon L.) seed flour 130:167 Belinjau (Gnetum gnemon L.) seed flour 130:167 Belinjau (Gnetum gnemon L.) seed flour was evaluated for nutritional composition, antioxidant activity and functional properties. 24629936 1 8 theme antioxidant 212:222 arg1 activity 224:231 antioxidant activity 212:231 antioxidant activity 212:231 Belinjau (Gnetum gnemon L.) seed flour was evaluated for nutritional composition, antioxidant activity and functional properties. 24629936 6 9 theme FTIR 1133:1136 arg1 analysis 1147:1154 FTIR spectral analysis 1133:1154 FTIR spectral analysis 1133:1154 FTIR spectral analysis showed seed flour to encompass major functional groups such as: amines, amides, amino acids, polysaccharides, carboxylic acids, esters and lipids. 24629936 4 10 from extracts 733:740 arg1 high 717:720 high 717:720 high 717:720 Inhibition of DPPH was high in ethanol extracts (48.9%) compared to aqueous extracts (19.7%), whereas aqueous extracts showed a higher FRAP value compared to ethanol extracts (0.98 and 0.61mmolFe(II)/100g, respectively). 24629936 7 11 contain has 1367:1369 arg2 potential 1376:1384 high potential 1371:1384 high potential to be used as a basic raw material to develop new low cost nutritious functional foods 1371:1471 As belinjau seed flour possesses a rich nutraceutical value, it has high potential to be used as a basic raw material to develop new low cost nutritious functional foods. 24629936 7 11 contain has 1367:1369 arg1 it 1364:1365 it 1364:1365 it 1364:1365 As belinjau seed flour possesses a rich nutraceutical value, it has high potential to be used as a basic raw material to develop new low cost nutritious functional foods. 24629936 2 12 theme Seed 260:263 arg1 flour 265:269 Seed flour 260:269 Seed flour 260:269 Seed flour was found to be rich in protein (19.0g/100g), crude fibre (8.66g/100g), carbohydrates (64.1%), total dietary fibre (14.5%) and encompassed adequate amounts of essential amino acids, fatty acids and minerals. 24629936 4 13 dep high 717:720 arg1 whereas 788:794 whereas 788:794 whereas 788:794 Inhibition of DPPH was high in ethanol extracts (48.9%) compared to aqueous extracts (19.7%), whereas aqueous extracts showed a higher FRAP value compared to ethanol extracts (0.98 and 0.61mmolFe(II)/100g, respectively). 24629936 4 13 dep high 717:720 arg1 % 784:784 19.7% 780:784 19.7% 780:784 Inhibition of DPPH was high in ethanol extracts (48.9%) compared to aqueous extracts (19.7%), whereas aqueous extracts showed a higher FRAP value compared to ethanol extracts (0.98 and 0.61mmolFe(II)/100g, respectively). 24629936 2 14 from protein 295:301 arg1 rich 287:290 rich 287:290 rich 287:290 Seed flour was found to be rich in protein (19.0g/100g), crude fibre (8.66g/100g), carbohydrates (64.1%), total dietary fibre (14.5%) and encompassed adequate amounts of essential amino acids, fatty acids and minerals. 24629936 5 15 theme foaming 1107:1113 arg1 capacity 1115:1122 foaming capacity 1107:1122 foaming capacity (5.78%) 1107:1130 Results on functional properties revealed acceptable water and oil absorption capacities (5.51 and 1.98g/g, respectively), emulsion capacity and stability (15.3% and 6.90%, respectively), and foaming capacity (5.78%). 24629936 5 15 theme foaming 1107:1113 arg1 % 1129:1129 5.78% 1125:1129 5.78% 1125:1129 Results on functional properties revealed acceptable water and oil absorption capacities (5.51 and 1.98g/g, respectively), emulsion capacity and stability (15.3% and 6.90%, respectively), and foaming capacity (5.78%). 24629936 2 16 theme adequate 410:417 arg1 acids 446:450 essential amino acids 430:450 essential amino acids 430:450 Seed flour was found to be rich in protein (19.0g/100g), crude fibre (8.66g/100g), carbohydrates (64.1%), total dietary fibre (14.5%) and encompassed adequate amounts of essential amino acids, fatty acids and minerals. 24629936 2 16 theme adequate 410:417 arg1 acids 459:463 fatty acids 453:463 fatty acids 453:463 Seed flour was found to be rich in protein (19.0g/100g), crude fibre (8.66g/100g), carbohydrates (64.1%), total dietary fibre (14.5%) and encompassed adequate amounts of essential amino acids, fatty acids and minerals. 24629936 2 16 theme adequate 410:417 arg1 amounts 419:425 adequate amounts 410:425 adequate amounts of essential amino acids, fatty acids and minerals 410:476 Seed flour was found to be rich in protein (19.0g/100g), crude fibre (8.66g/100g), carbohydrates (64.1%), total dietary fibre (14.5%) and encompassed adequate amounts of essential amino acids, fatty acids and minerals. 24629936 2 16 theme adequate 410:417 arg1 minerals 469:476 minerals 469:476 minerals 469:476 Seed flour was found to be rich in protein (19.0g/100g), crude fibre (8.66g/100g), carbohydrates (64.1%), total dietary fibre (14.5%) and encompassed adequate amounts of essential amino acids, fatty acids and minerals. 24629936 7 17 theme cost 1440:1443 arg1 foods 1467:1471 new low cost nutritious functional foods 1432:1471 new low cost nutritious functional foods 1432:1471 As belinjau seed flour possesses a rich nutraceutical value, it has high potential to be used as a basic raw material to develop new low cost nutritious functional foods. 24629936 5 18 dep water 968:972 arg1 1.98g/g 1014:1020 1.98g/g 1014:1020 1.98g/g 1014:1020 Results on functional properties revealed acceptable water and oil absorption capacities (5.51 and 1.98g/g, respectively), emulsion capacity and stability (15.3% and 6.90%, respectively), and foaming capacity (5.78%). 24629936 5 18 dep water 968:972 arg1 5.51 1005:1008 5.51 1005:1008 5.51 1005:1008 Results on functional properties revealed acceptable water and oil absorption capacities (5.51 and 1.98g/g, respectively), emulsion capacity and stability (15.3% and 6.90%, respectively), and foaming capacity (5.78%). 24629936 7 19 theme nutritious 1445:1454 arg1 foods 1467:1471 new low cost nutritious functional foods 1432:1471 new low cost nutritious functional foods 1432:1471 As belinjau seed flour possesses a rich nutraceutical value, it has high potential to be used as a basic raw material to develop new low cost nutritious functional foods. 24629936 4 20 from high 717:720 arg1 extracts 733:740 ethanol extracts 725:740 ethanol extracts (48.9%) 725:748 Inhibition of DPPH was high in ethanol extracts (48.9%) compared to aqueous extracts (19.7%), whereas aqueous extracts showed a higher FRAP value compared to ethanol extracts (0.98 and 0.61mmolFe(II)/100g, respectively). 24629936 4 20 from high 717:720 arg1 % 747:747 48.9% 743:747 48.9% 743:747 Inhibition of DPPH was high in ethanol extracts (48.9%) compared to aqueous extracts (19.7%), whereas aqueous extracts showed a higher FRAP value compared to ethanol extracts (0.98 and 0.61mmolFe(II)/100g, respectively). 24629936 7 21 theme rich 1338:1341 arg1 value 1357:1361 a rich nutraceutical value 1336:1361 a rich nutraceutical value 1336:1361 As belinjau seed flour possesses a rich nutraceutical value, it has high potential to be used as a basic raw material to develop new low cost nutritious functional foods. 24629936 7 22 theme basic 1402:1406 arg1 material 1412:1419 a basic raw material 1400:1419 a basic raw material 1400:1419 As belinjau seed flour possesses a rich nutraceutical value, it has high potential to be used as a basic raw material to develop new low cost nutritious functional foods. 24629936 1 23 theme Gnetum 140:145 arg1 gnemon 147:152 Gnetum gnemon 140:152 Gnetum gnemon L. 140:155 Belinjau (Gnetum gnemon L.) seed flour was evaluated for nutritional composition, antioxidant activity and functional properties. 24629936 1 23 theme Gnetum 140:145 arg1 L. 154:155 L. 154:155 L. 154:155 Belinjau (Gnetum gnemon L.) seed flour was evaluated for nutritional composition, antioxidant activity and functional properties. 24629936 5 24 from Results 915:921 arg1 properties 937:946 functional properties 926:946 functional properties 926:946 Results on functional properties revealed acceptable water and oil absorption capacities (5.51 and 1.98g/g, respectively), emulsion capacity and stability (15.3% and 6.90%, respectively), and foaming capacity (5.78%). 24629936 6 25 theme spectral 1138:1145 arg1 analysis 1147:1154 FTIR spectral analysis 1133:1154 FTIR spectral analysis 1133:1154 FTIR spectral analysis showed seed flour to encompass major functional groups such as: amines, amides, amino acids, polysaccharides, carboxylic acids, esters and lipids. 24629936 4 26 theme ethanol 725:731 arg1 extracts 733:740 ethanol extracts 725:740 ethanol extracts (48.9%) 725:748 Inhibition of DPPH was high in ethanol extracts (48.9%) compared to aqueous extracts (19.7%), whereas aqueous extracts showed a higher FRAP value compared to ethanol extracts (0.98 and 0.61mmolFe(II)/100g, respectively). 24629936 4 26 theme ethanol 725:731 arg1 % 747:747 48.9% 743:747 48.9% 743:747 Inhibition of DPPH was high in ethanol extracts (48.9%) compared to aqueous extracts (19.7%), whereas aqueous extracts showed a higher FRAP value compared to ethanol extracts (0.98 and 0.61mmolFe(II)/100g, respectively). 24629936 7 27 theme raw 1408:1410 arg1 material 1412:1419 a basic raw material 1400:1419 a basic raw material 1400:1419 As belinjau seed flour possesses a rich nutraceutical value, it has high potential to be used as a basic raw material to develop new low cost nutritious functional foods. 24629936 4 28 theme ethanol 852:858 arg1 extracts 860:867 ethanol extracts 852:867 ethanol extracts (0.98 and 0.61mmolFe(II)/100g, respectively) 852:912 Inhibition of DPPH was high in ethanol extracts (48.9%) compared to aqueous extracts (19.7%), whereas aqueous extracts showed a higher FRAP value compared to ethanol extracts (0.98 and 0.61mmolFe(II)/100g, respectively). 24629936 1 29 theme functional 237:246 arg1 properties 248:257 functional properties 237:257 functional properties 237:257 Belinjau (Gnetum gnemon L.) seed flour was evaluated for nutritional composition, antioxidant activity and functional properties. 24629936 1 30 dep Belinjau 130:137 arg1 gnemon 147:152 Gnetum gnemon 140:152 Gnetum gnemon L. 140:155 Belinjau (Gnetum gnemon L.) seed flour was evaluated for nutritional composition, antioxidant activity and functional properties. 24629936 1 30 dep Belinjau 130:137 arg1 L. 154:155 L. 154:155 L. 154:155 Belinjau (Gnetum gnemon L.) seed flour was evaluated for nutritional composition, antioxidant activity and functional properties. 24629936 0 31 theme Gnetum 21:26 arg1 gnemon 28:33 Gnetum gnemon L. 21:36 Gnetum gnemon L. 21:36 Evaluating belinjau (Gnetum gnemon L.) seed flour quality as a base for development of novel food products and food formulations. 24629936 0 32 theme food 93:96 arg1 products 98:105 novel food products 87:105 novel food products 87:105 Evaluating belinjau (Gnetum gnemon L.) seed flour quality as a base for development of novel food products and food formulations. 24629936 3 33 theme Antioxidant 479:489 arg1 compounds 491:499 Antioxidant compounds 479:499 Antioxidant compounds such as total phenols (15.1 and 12.6mgGAE/100g), tannins (35.6 and 16.1mgCE/100g) and flavonoids (709 and 81.6mgCEQ/100g) 479:621 Antioxidant compounds such as total phenols (15.1 and 12.6mgGAE/100g), tannins (35.6 and 16.1mgCE/100g) and flavonoids (709 and 81.6mgCEQ/100g) were higher in ethanolic extracts over aqueous extracts, respectively. 24629936 3 33 theme Antioxidant 479:489 arg1 tannins 550:556 tannins 550:556 tannins (35.6 and 16.1mgCE/100g) 550:581 Antioxidant compounds such as total phenols (15.1 and 12.6mgGAE/100g), tannins (35.6 and 16.1mgCE/100g) and flavonoids (709 and 81.6mgCEQ/100g) were higher in ethanolic extracts over aqueous extracts, respectively. 24629936 3 33 theme Antioxidant 479:489 arg1 phenols 515:521 total phenols 509:521 total phenols (15.1 and 12.6mgGAE/100g) 509:547 Antioxidant compounds such as total phenols (15.1 and 12.6mgGAE/100g), tannins (35.6 and 16.1mgCE/100g) and flavonoids (709 and 81.6mgCEQ/100g) were higher in ethanolic extracts over aqueous extracts, respectively. 24629936 3 33 theme Antioxidant 479:489 arg1 flavonoids 587:596 flavonoids 587:596 flavonoids (709 and 81.6mgCEQ/100g) 587:621 Antioxidant compounds such as total phenols (15.1 and 12.6mgGAE/100g), tannins (35.6 and 16.1mgCE/100g) and flavonoids (709 and 81.6mgCEQ/100g) were higher in ethanolic extracts over aqueous extracts, respectively. 24629936 6 34 theme carboxylic 1266:1275 arg1 acids 1277:1281 carboxylic acids 1266:1281 carboxylic acids 1266:1281 FTIR spectral analysis showed seed flour to encompass major functional groups such as: amines, amides, amino acids, polysaccharides, carboxylic acids, esters and lipids. 24629936 6 35 theme functional 1193:1202 arg1 groups 1204:1209 major functional groups 1187:1209 major functional groups such as: amines, amides, amino acids, polysaccharides, carboxylic acids, esters and lipids 1187:1300 FTIR spectral analysis showed seed flour to encompass major functional groups such as: amines, amides, amino acids, polysaccharides, carboxylic acids, esters and lipids. 24629936 7 36 theme seed 1315:1318 arg1 flour 1320:1324 belinjau seed flour 1306:1324 belinjau seed flour 1306:1324 As belinjau seed flour possesses a rich nutraceutical value, it has high potential to be used as a basic raw material to develop new low cost nutritious functional foods. 24629936 0 37 theme novel 87:91 arg1 products 98:105 novel food products 87:105 novel food products 87:105 Evaluating belinjau (Gnetum gnemon L.) seed flour quality as a base for development of novel food products and food formulations. 24629936 5 38 dep capacity 1047:1054 arg1 % 1075:1075 15.3% 1071:1075 15.3% 1071:1075 Results on functional properties revealed acceptable water and oil absorption capacities (5.51 and 1.98g/g, respectively), emulsion capacity and stability (15.3% and 6.90%, respectively), and foaming capacity (5.78%). 24629936 5 38 dep capacity 1047:1054 arg1 % 1085:1085 6.90% 1081:1085 6.90% 1081:1085 Results on functional properties revealed acceptable water and oil absorption capacities (5.51 and 1.98g/g, respectively), emulsion capacity and stability (15.3% and 6.90%, respectively), and foaming capacity (5.78%). 24629936 1 39 theme seed 158:161 arg1 flour 163:167 Belinjau (Gnetum gnemon L.) seed flour 130:167 Belinjau (Gnetum gnemon L.) seed flour 130:167 Belinjau (Gnetum gnemon L.) seed flour was evaluated for nutritional composition, antioxidant activity and functional properties. 24629936 6 40 theme major 1187:1191 arg1 groups 1204:1209 major functional groups 1187:1209 major functional groups such as: amines, amides, amino acids, polysaccharides, carboxylic acids, esters and lipids 1187:1300 FTIR spectral analysis showed seed flour to encompass major functional groups such as: amines, amides, amino acids, polysaccharides, carboxylic acids, esters and lipids. 24629936 7 41 theme high 1371:1374 arg1 potential 1376:1384 high potential 1371:1384 high potential to be used as a basic raw material to develop new low cost nutritious functional foods 1371:1471 As belinjau seed flour possesses a rich nutraceutical value, it has high potential to be used as a basic raw material to develop new low cost nutritious functional foods. 24629936 2 42 theme amino 440:444 arg1 acids 446:450 essential amino acids 430:450 essential amino acids 430:450 Seed flour was found to be rich in protein (19.0g/100g), crude fibre (8.66g/100g), carbohydrates (64.1%), total dietary fibre (14.5%) and encompassed adequate amounts of essential amino acids, fatty acids and minerals. 24629936 0 43 dep seed 39:42 arg1 gnemon 28:33 Gnetum gnemon L. 21:36 Gnetum gnemon L. 21:36 Evaluating belinjau (Gnetum gnemon L.) seed flour quality as a base for development of novel food products and food formulations. 24629936 3 44 dep phenols 515:521 arg1 12.6mgGAE/100g 533:546 12.6mgGAE/100g 533:546 12.6mgGAE/100g 533:546 Antioxidant compounds such as total phenols (15.1 and 12.6mgGAE/100g), tannins (35.6 and 16.1mgCE/100g) and flavonoids (709 and 81.6mgCEQ/100g) were higher in ethanolic extracts over aqueous extracts, respectively. 24629936 3 44 dep phenols 515:521 arg1 15.1 524:527 15.1 524:527 15.1 524:527 Antioxidant compounds such as total phenols (15.1 and 12.6mgGAE/100g), tannins (35.6 and 16.1mgCE/100g) and flavonoids (709 and 81.6mgCEQ/100g) were higher in ethanolic extracts over aqueous extracts, respectively. 24629936 4 45 theme FRAP 829:832 arg1 value 834:838 a higher FRAP value 820:838 a higher FRAP value 820:838 Inhibition of DPPH was high in ethanol extracts (48.9%) compared to aqueous extracts (19.7%), whereas aqueous extracts showed a higher FRAP value compared to ethanol extracts (0.98 and 0.61mmolFe(II)/100g, respectively). 24629936 3 46 dep flavonoids 587:596 arg1 81.6mgCEQ/100g 607:620 81.6mgCEQ/100g 607:620 81.6mgCEQ/100g 607:620 Antioxidant compounds such as total phenols (15.1 and 12.6mgGAE/100g), tannins (35.6 and 16.1mgCE/100g) and flavonoids (709 and 81.6mgCEQ/100g) were higher in ethanolic extracts over aqueous extracts, respectively. 24629936 3 46 dep flavonoids 587:596 arg1 709 599:601 709 599:601 709 599:601 Antioxidant compounds such as total phenols (15.1 and 12.6mgGAE/100g), tannins (35.6 and 16.1mgCE/100g) and flavonoids (709 and 81.6mgCEQ/100g) were higher in ethanolic extracts over aqueous extracts, respectively. 24629936 0 47 theme products 98:105 arg1 development 72:82 development 72:82 development of novel food products and food formulations 72:127 Evaluating belinjau (Gnetum gnemon L.) seed flour quality as a base for development of novel food products and food formulations. 24629936 3 48 theme aqueous 662:668 arg1 extracts 670:677 aqueous extracts 662:677 aqueous extracts 662:677 Antioxidant compounds such as total phenols (15.1 and 12.6mgGAE/100g), tannins (35.6 and 16.1mgCE/100g) and flavonoids (709 and 81.6mgCEQ/100g) were higher in ethanolic extracts over aqueous extracts, respectively. 24629936 5 49 theme absorption 982:991 arg1 capacities 993:1002 oil absorption capacities 978:1002 oil absorption capacities 978:1002 Results on functional properties revealed acceptable water and oil absorption capacities (5.51 and 1.98g/g, respectively), emulsion capacity and stability (15.3% and 6.90%, respectively), and foaming capacity (5.78%). 24629936 0 50 theme seed 39:42 arg1 quality 50:56 belinjau (Gnetum gnemon L.) seed flour quality 11:56 belinjau (Gnetum gnemon L.) seed flour quality 11:56 Evaluating belinjau (Gnetum gnemon L.) seed flour quality as a base for development of novel food products and food formulations. 24629936 0 50 theme seed 39:42 arg1 base 63:66 a base 61:66 a base for development of novel food products and food formulations 61:127 Evaluating belinjau (Gnetum gnemon L.) seed flour quality as a base for development of novel food products and food formulations. 24629936 2 51 theme minerals 469:476 arg1 acids 446:450 essential amino acids 430:450 essential amino acids 430:450 Seed flour was found to be rich in protein (19.0g/100g), crude fibre (8.66g/100g), carbohydrates (64.1%), total dietary fibre (14.5%) and encompassed adequate amounts of essential amino acids, fatty acids and minerals. 24629936 2 51 theme minerals 469:476 arg1 acids 459:463 fatty acids 453:463 fatty acids 453:463 Seed flour was found to be rich in protein (19.0g/100g), crude fibre (8.66g/100g), carbohydrates (64.1%), total dietary fibre (14.5%) and encompassed adequate amounts of essential amino acids, fatty acids and minerals. 24629936 2 51 theme minerals 469:476 arg1 amounts 419:425 adequate amounts 410:425 adequate amounts of essential amino acids, fatty acids and minerals 410:476 Seed flour was found to be rich in protein (19.0g/100g), crude fibre (8.66g/100g), carbohydrates (64.1%), total dietary fibre (14.5%) and encompassed adequate amounts of essential amino acids, fatty acids and minerals. 24629936 2 51 theme minerals 469:476 arg1 minerals 469:476 minerals 469:476 minerals 469:476 Seed flour was found to be rich in protein (19.0g/100g), crude fibre (8.66g/100g), carbohydrates (64.1%), total dietary fibre (14.5%) and encompassed adequate amounts of essential amino acids, fatty acids and minerals. 24629936 4 52 theme DPPH 708:711 arg1 Inhibition 694:703 Inhibition 694:703 Inhibition of DPPH 694:711 Inhibition of DPPH was high in ethanol extracts (48.9%) compared to aqueous extracts (19.7%), whereas aqueous extracts showed a higher FRAP value compared to ethanol extracts (0.98 and 0.61mmolFe(II)/100g, respectively). 24629936 4 53 theme aqueous 762:768 arg1 extracts 770:777 aqueous extracts 762:777 aqueous extracts 762:777 Inhibition of DPPH was high in ethanol extracts (48.9%) compared to aqueous extracts (19.7%), whereas aqueous extracts showed a higher FRAP value compared to ethanol extracts (0.98 and 0.61mmolFe(II)/100g, respectively). 24629936 2 54 theme essential 430:438 arg1 acids 446:450 essential amino acids 430:450 essential amino acids 430:450 Seed flour was found to be rich in protein (19.0g/100g), crude fibre (8.66g/100g), carbohydrates (64.1%), total dietary fibre (14.5%) and encompassed adequate amounts of essential amino acids, fatty acids and minerals. 24629936 5 55 theme oil 978:980 arg1 capacities 993:1002 oil absorption capacities 978:1002 oil absorption capacities 978:1002 Results on functional properties revealed acceptable water and oil absorption capacities (5.51 and 1.98g/g, respectively), emulsion capacity and stability (15.3% and 6.90%, respectively), and foaming capacity (5.78%). 24629936 0 56 theme food 111:114 arg1 formulations 116:127 food formulations 111:127 food formulations 111:127 Evaluating belinjau (Gnetum gnemon L.) seed flour quality as a base for development of novel food products and food formulations. 24629936 0 57 dep gnemon 28:33 arg1 L. 35:36 L. 35:36 L. 35:36 Evaluating belinjau (Gnetum gnemon L.) seed flour quality as a base for development of novel food products and food formulations. 24629936 4 58 theme aqueous 796:802 arg1 extracts 804:811 aqueous extracts 796:811 aqueous extracts 796:811 Inhibition of DPPH was high in ethanol extracts (48.9%) compared to aqueous extracts (19.7%), whereas aqueous extracts showed a higher FRAP value compared to ethanol extracts (0.98 and 0.61mmolFe(II)/100g, respectively). 24629936 3 59 theme ethanolic 638:646 arg1 extracts 648:655 ethanolic extracts 638:655 ethanolic extracts 638:655 Antioxidant compounds such as total phenols (15.1 and 12.6mgGAE/100g), tannins (35.6 and 16.1mgCE/100g) and flavonoids (709 and 81.6mgCEQ/100g) were higher in ethanolic extracts over aqueous extracts, respectively. 24629936 2 60 theme acids 459:463 arg1 acids 446:450 essential amino acids 430:450 essential amino acids 430:450 Seed flour was found to be rich in protein (19.0g/100g), crude fibre (8.66g/100g), carbohydrates (64.1%), total dietary fibre (14.5%) and encompassed adequate amounts of essential amino acids, fatty acids and minerals. 24629936 2 60 theme acids 459:463 arg1 acids 459:463 fatty acids 453:463 fatty acids 453:463 Seed flour was found to be rich in protein (19.0g/100g), crude fibre (8.66g/100g), carbohydrates (64.1%), total dietary fibre (14.5%) and encompassed adequate amounts of essential amino acids, fatty acids and minerals. 24629936 2 60 theme acids 459:463 arg1 amounts 419:425 adequate amounts 410:425 adequate amounts of essential amino acids, fatty acids and minerals 410:476 Seed flour was found to be rich in protein (19.0g/100g), crude fibre (8.66g/100g), carbohydrates (64.1%), total dietary fibre (14.5%) and encompassed adequate amounts of essential amino acids, fatty acids and minerals. 24629936 2 60 theme acids 459:463 arg1 minerals 469:476 minerals 469:476 minerals 469:476 Seed flour was found to be rich in protein (19.0g/100g), crude fibre (8.66g/100g), carbohydrates (64.1%), total dietary fibre (14.5%) and encompassed adequate amounts of essential amino acids, fatty acids and minerals. 24629936 7 61 contain possesses 1326:1334 arg2 value 1357:1361 a rich nutraceutical value 1336:1361 a rich nutraceutical value 1336:1361 As belinjau seed flour possesses a rich nutraceutical value, it has high potential to be used as a basic raw material to develop new low cost nutritious functional foods. 24629936 7 61 contain possesses 1326:1334 arg1 flour 1320:1324 belinjau seed flour 1306:1324 belinjau seed flour 1306:1324 As belinjau seed flour possesses a rich nutraceutical value, it has high potential to be used as a basic raw material to develop new low cost nutritious functional foods. 24629936 2 62 theme fatty 453:457 arg1 acids 459:463 fatty acids 453:463 fatty acids 453:463 Seed flour was found to be rich in protein (19.0g/100g), crude fibre (8.66g/100g), carbohydrates (64.1%), total dietary fibre (14.5%) and encompassed adequate amounts of essential amino acids, fatty acids and minerals. 24629936 3 63 dep tannins 550:556 arg1 16.1mgCE/100g 568:580 16.1mgCE/100g 568:580 16.1mgCE/100g 568:580 Antioxidant compounds such as total phenols (15.1 and 12.6mgGAE/100g), tannins (35.6 and 16.1mgCE/100g) and flavonoids (709 and 81.6mgCEQ/100g) were higher in ethanolic extracts over aqueous extracts, respectively. 24629936 3 63 dep tannins 550:556 arg1 35.6 559:562 35.6 559:562 35.6 559:562 Antioxidant compounds such as total phenols (15.1 and 12.6mgGAE/100g), tannins (35.6 and 16.1mgCE/100g) and flavonoids (709 and 81.6mgCEQ/100g) were higher in ethanolic extracts over aqueous extracts, respectively. 24629936 6 64 theme amino 1236:1240 arg1 acids 1242:1246 amino acids 1236:1246 amino acids 1236:1246 FTIR spectral analysis showed seed flour to encompass major functional groups such as: amines, amides, amino acids, polysaccharides, carboxylic acids, esters and lipids. 24629936 5 65 theme emulsion 1038:1045 arg1 capacity 1047:1054 emulsion capacity 1038:1054 emulsion capacity 1038:1054 Results on functional properties revealed acceptable water and oil absorption capacities (5.51 and 1.98g/g, respectively), emulsion capacity and stability (15.3% and 6.90%, respectively), and foaming capacity (5.78%). 24629936 6 66 theme seed 1163:1166 arg1 flour 1168:1172 seed flour 1163:1172 seed flour to encompass major functional groups such as: amines, amides, amino acids, polysaccharides, carboxylic acids, esters and lipids 1163:1300 FTIR spectral analysis showed seed flour to encompass major functional groups such as: amines, amides, amino acids, polysaccharides, carboxylic acids, esters and lipids. 24629936 7 67 theme new 1432:1434 arg1 foods 1467:1471 new low cost nutritious functional foods 1432:1471 new low cost nutritious functional foods 1432:1471 As belinjau seed flour possesses a rich nutraceutical value, it has high potential to be used as a basic raw material to develop new low cost nutritious functional foods. 24629936 5 68 theme acceptable 957:966 arg1 water 968:972 acceptable water 957:972 acceptable water 957:972 Results on functional properties revealed acceptable water and oil absorption capacities (5.51 and 1.98g/g, respectively), emulsion capacity and stability (15.3% and 6.90%, respectively), and foaming capacity (5.78%). 24629936 7 69 theme low 1436:1438 arg1 foods 1467:1471 new low cost nutritious functional foods 1432:1471 new low cost nutritious functional foods 1432:1471 As belinjau seed flour possesses a rich nutraceutical value, it has high potential to be used as a basic raw material to develop new low cost nutritious functional foods. 24629936 7 70 theme functional 1456:1465 arg1 foods 1467:1471 new low cost nutritious functional foods 1432:1471 new low cost nutritious functional foods 1432:1471 As belinjau seed flour possesses a rich nutraceutical value, it has high potential to be used as a basic raw material to develop new low cost nutritious functional foods. 24629936 1 71 theme nutritional 187:197 arg1 composition 199:209 nutritional composition 187:209 nutritional composition 187:209 Belinjau (Gnetum gnemon L.) seed flour was evaluated for nutritional composition, antioxidant activity and functional properties. 24629936 0 72 theme flour 44:48 arg1 quality 50:56 belinjau (Gnetum gnemon L.) seed flour quality 11:56 belinjau (Gnetum gnemon L.) seed flour quality 11:56 Evaluating belinjau (Gnetum gnemon L.) seed flour quality as a base for development of novel food products and food formulations. 24629936 0 72 theme flour 44:48 arg1 base 63:66 a base 61:66 a base for development of novel food products and food formulations 61:127 Evaluating belinjau (Gnetum gnemon L.) seed flour quality as a base for development of novel food products and food formulations. 24629936 5 73 theme functional 926:935 arg1 properties 937:946 functional properties 926:946 functional properties 926:946 Results on functional properties revealed acceptable water and oil absorption capacities (5.51 and 1.98g/g, respectively), emulsion capacity and stability (15.3% and 6.90%, respectively), and foaming capacity (5.78%). 24629936 3 74 theme total 509:513 arg1 phenols 515:521 total phenols 509:521 total phenols (15.1 and 12.6mgGAE/100g) 509:547 Antioxidant compounds such as total phenols (15.1 and 12.6mgGAE/100g), tannins (35.6 and 16.1mgCE/100g) and flavonoids (709 and 81.6mgCEQ/100g) were higher in ethanolic extracts over aqueous extracts, respectively. 24629936 4 75 theme 0.61mmolFe 879:888 arg1 /100g 893:897 0.61mmolFe(II)/100g 879:897 0.61mmolFe(II)/100g 879:897 Inhibition of DPPH was high in ethanol extracts (48.9%) compared to aqueous extracts (19.7%), whereas aqueous extracts showed a higher FRAP value compared to ethanol extracts (0.98 and 0.61mmolFe(II)/100g, respectively). 24485322 2 0 theme pro-inflammatory 313:328 arg1 state 330:334 a more pro-inflammatory state 306:334 a more pro-inflammatory state compared with APOE3/E3 individuals 306:369 APOE4 carriers have been associated with higher blood lipid levels and a more pro-inflammatory state compared with APOE3/E3 individuals. 24485322 5 1 theme ex 1056:1057 arg1 production 1073:1082 ex vivo cytokine production 1056:1082 ex vivo cytokine production using whole blood culture (WBC) 1056:1114 Blood samples were collected from a subset of SATgenε participants (n=52/88), prospectively recruited according to APOE genotype (n=26 E3/E3 and n=26 E3/E4) after low-fat (LF), high saturated fat (HSF) and HSF with 3.45g docosahexaenoic acid (DHA) dietary periods (each diet eight weeks in duration assigned in the same order) for the measurement of ex vivo cytokine production using whole blood culture (WBC). 24485322 2 2 theme blood 283:287 arg1 levels 295:300 higher blood lipid levels 276:300 higher blood lipid levels 276:300 APOE4 carriers have been associated with higher blood lipid levels and a more pro-inflammatory state compared with APOE3/E3 individuals. 24485322 7 3 theme TNF-α 1449:1453 arg1 concentration 1455:1467 TNF-α concentration 1449:1467 TNF-α concentration 1449:1467 Cytokine levels were not influenced by genotype, whereas, dietary fat manipulation had a significant impact on TNF-α and IL-10 production; TNF-α concentration was higher after consumption of the HSF diet compared with baseline and the LF diet (P<0.05), whereas, IL-10 concentration was higher after the LF diet compared with baseline (P<0.05). 24485322 5 4 theme acid 943:946 arg1 periods 962:968 3.45g docosahexaenoic acid (DHA) dietary periods 921:968 3.45g docosahexaenoic acid (DHA) dietary periods (each diet eight weeks in duration assigned in the same order) 921:1031 Blood samples were collected from a subset of SATgenε participants (n=52/88), prospectively recruited according to APOE genotype (n=26 E3/E3 and n=26 E3/E4) after low-fat (LF), high saturated fat (HSF) and HSF with 3.45g docosahexaenoic acid (DHA) dietary periods (each diet eight weeks in duration assigned in the same order) for the measurement of ex vivo cytokine production using whole blood culture (WBC). 24485322 5 5 theme participants 760:771 arg1 subset 742:747 a subset 740:747 a subset of SATgenε participants (n=52/88) 740:781 Blood samples were collected from a subset of SATgenε participants (n=52/88), prospectively recruited according to APOE genotype (n=26 E3/E3 and n=26 E3/E4) after low-fat (LF), high saturated fat (HSF) and HSF with 3.45g docosahexaenoic acid (DHA) dietary periods (each diet eight weeks in duration assigned in the same order) for the measurement of ex vivo cytokine production using whole blood culture (WBC). 24485322 8 6 dep ex 1791:1792 arg1 vivo 1794:1797 vivo 1794:1797 vivo 1794:1797 In conclusion, our study has revealed the amount and type of dietary fat can significantly modulate the production of TNF-α and IL-10 by ex vivo LPS-stimulated WBC samples obtained from normolipidaemic subjects. 24485322 5 7 theme DHA 949:951 arg1 periods 962:968 3.45g docosahexaenoic acid (DHA) dietary periods 921:968 3.45g docosahexaenoic acid (DHA) dietary periods (each diet eight weeks in duration assigned in the same order) 921:1031 Blood samples were collected from a subset of SATgenε participants (n=52/88), prospectively recruited according to APOE genotype (n=26 E3/E3 and n=26 E3/E4) after low-fat (LF), high saturated fat (HSF) and HSF with 3.45g docosahexaenoic acid (DHA) dietary periods (each diet eight weeks in duration assigned in the same order) for the measurement of ex vivo cytokine production using whole blood culture (WBC). 24485322 8 8 theme IL-10 1782:1786 arg1 production 1758:1767 the production 1754:1767 the production of TNF-α and IL-10 by ex vivo LPS-stimulated WBC samples obtained from normolipidaemic subjects 1754:1863 In conclusion, our study has revealed the amount and type of dietary fat can significantly modulate the production of TNF-α and IL-10 by ex vivo LPS-stimulated WBC samples obtained from normolipidaemic subjects. 24485322 7 9 theme LF 1545:1546 arg1 P<0.05 1554:1559 P<0.05 1554:1559 P<0.05 1554:1559 Cytokine levels were not influenced by genotype, whereas, dietary fat manipulation had a significant impact on TNF-α and IL-10 production; TNF-α concentration was higher after consumption of the HSF diet compared with baseline and the LF diet (P<0.05), whereas, IL-10 concentration was higher after the LF diet compared with baseline (P<0.05). 24485322 7 9 theme LF 1545:1546 arg1 diet 1548:1551 the LF diet 1541:1551 the LF diet (P<0.05) 1541:1560 Cytokine levels were not influenced by genotype, whereas, dietary fat manipulation had a significant impact on TNF-α and IL-10 production; TNF-α concentration was higher after consumption of the HSF diet compared with baseline and the LF diet (P<0.05), whereas, IL-10 concentration was higher after the LF diet compared with baseline (P<0.05). 24485322 5 10 dep ex 1056:1057 arg1 vivo 1059:1062 vivo 1059:1062 vivo 1059:1062 Blood samples were collected from a subset of SATgenε participants (n=52/88), prospectively recruited according to APOE genotype (n=26 E3/E3 and n=26 E3/E4) after low-fat (LF), high saturated fat (HSF) and HSF with 3.45g docosahexaenoic acid (DHA) dietary periods (each diet eight weeks in duration assigned in the same order) for the measurement of ex vivo cytokine production using whole blood culture (WBC). 24485322 4 11 theme dietary 649:655 arg1 fat 657:659 dietary fat 649:659 dietary fat 649:659 In a follow-up to the main SATgenε study, we aimed to explore the effects of APOE genotype, as well as, dietary fat manipulation on ex vivo cytokine production. 24485322 5 12 theme 3.45g 921:925 arg1 periods 962:968 3.45g docosahexaenoic acid (DHA) dietary periods 921:968 3.45g docosahexaenoic acid (DHA) dietary periods (each diet eight weeks in duration assigned in the same order) 921:1031 Blood samples were collected from a subset of SATgenε participants (n=52/88), prospectively recruited according to APOE genotype (n=26 E3/E3 and n=26 E3/E4) after low-fat (LF), high saturated fat (HSF) and HSF with 3.45g docosahexaenoic acid (DHA) dietary periods (each diet eight weeks in duration assigned in the same order) for the measurement of ex vivo cytokine production using whole blood culture (WBC). 24485322 7 13 theme significant 1399:1409 arg1 impact 1411:1416 a significant impact 1397:1416 a significant impact 1397:1416 Cytokine levels were not influenced by genotype, whereas, dietary fat manipulation had a significant impact on TNF-α and IL-10 production; TNF-α concentration was higher after consumption of the HSF diet compared with baseline and the LF diet (P<0.05), whereas, IL-10 concentration was higher after the LF diet compared with baseline (P<0.05). 24485322 4 14 theme genotype 627:634 arg1 effects 611:617 the effects 607:617 the effects of APOE genotype, as well as, dietary fat manipulation on ex vivo cytokine production 607:703 In a follow-up to the main SATgenε study, we aimed to explore the effects of APOE genotype, as well as, dietary fat manipulation on ex vivo cytokine production. 24485322 6 15 theme supernatant 1198:1208 arg1 samples 1210:1216 WBC supernatant samples 1194:1216 WBC supernatant samples 1194:1216 Concentrations of IL-1beta, IL-6, IL-8, IL-10 and TNF-alpha were measured in WBC supernatant samples after stimulation for 24h with either 0.05 or 1μg/ml of bacterial lipopolysaccharide (LPS). 24485322 5 16 theme diet 976:979 arg1 weeks 987:991 each diet eight weeks 971:991 each diet eight weeks in duration assigned in the same order 971:1030 Blood samples were collected from a subset of SATgenε participants (n=52/88), prospectively recruited according to APOE genotype (n=26 E3/E3 and n=26 E3/E4) after low-fat (LF), high saturated fat (HSF) and HSF with 3.45g docosahexaenoic acid (DHA) dietary periods (each diet eight weeks in duration assigned in the same order) for the measurement of ex vivo cytokine production using whole blood culture (WBC). 24485322 5 17 theme blood 1096:1100 arg1 culture 1102:1108 whole blood culture 1090:1108 whole blood culture (WBC) 1090:1114 Blood samples were collected from a subset of SATgenε participants (n=52/88), prospectively recruited according to APOE genotype (n=26 E3/E3 and n=26 E3/E4) after low-fat (LF), high saturated fat (HSF) and HSF with 3.45g docosahexaenoic acid (DHA) dietary periods (each diet eight weeks in duration assigned in the same order) for the measurement of ex vivo cytokine production using whole blood culture (WBC). 24485322 5 17 theme blood 1096:1100 arg1 WBC 1111:1113 WBC 1111:1113 WBC 1111:1113 Blood samples were collected from a subset of SATgenε participants (n=52/88), prospectively recruited according to APOE genotype (n=26 E3/E3 and n=26 E3/E4) after low-fat (LF), high saturated fat (HSF) and HSF with 3.45g docosahexaenoic acid (DHA) dietary periods (each diet eight weeks in duration assigned in the same order) for the measurement of ex vivo cytokine production using whole blood culture (WBC). 24485322 8 18 theme fat 1723:1725 arg1 fat 1723:1725 dietary fat 1715:1725 dietary fat 1715:1725 In conclusion, our study has revealed the amount and type of dietary fat can significantly modulate the production of TNF-α and IL-10 by ex vivo LPS-stimulated WBC samples obtained from normolipidaemic subjects. 24485322 8 18 theme fat 1723:1725 arg1 amount 1696:1701 amount 1696:1701 amount 1696:1701 In conclusion, our study has revealed the amount and type of dietary fat can significantly modulate the production of TNF-α and IL-10 by ex vivo LPS-stimulated WBC samples obtained from normolipidaemic subjects. 24485322 8 18 theme fat 1723:1725 arg1 type 1707:1710 type 1707:1710 type 1707:1710 In conclusion, our study has revealed the amount and type of dietary fat can significantly modulate the production of TNF-α and IL-10 by ex vivo LPS-stimulated WBC samples obtained from normolipidaemic subjects. 24485322 1 19 theme E 155:155 arg1 genotype 164:171 Apolipoprotein E (APOE) genotype 140:171 Apolipoprotein E (APOE) genotype 140:171 Apolipoprotein E (APOE) genotype is believed to play an important role in cardiovascular risk. 24485322 7 20 theme diet 1509:1512 arg1 consumption 1486:1496 consumption 1486:1496 consumption of the HSF diet compared with baseline and the LF diet (P<0.05) 1486:1560 Cytokine levels were not influenced by genotype, whereas, dietary fat manipulation had a significant impact on TNF-α and IL-10 production; TNF-α concentration was higher after consumption of the HSF diet compared with baseline and the LF diet (P<0.05), whereas, IL-10 concentration was higher after the LF diet compared with baseline (P<0.05). 24485322 7 21 theme fat 1376:1378 arg1 manipulation 1380:1391 dietary fat manipulation 1368:1391 dietary fat manipulation 1368:1391 Cytokine levels were not influenced by genotype, whereas, dietary fat manipulation had a significant impact on TNF-α and IL-10 production; TNF-α concentration was higher after consumption of the HSF diet compared with baseline and the LF diet (P<0.05), whereas, IL-10 concentration was higher after the LF diet compared with baseline (P<0.05). 24485322 4 22 theme cytokine 685:692 arg1 production 694:703 ex vivo cytokine production 677:703 ex vivo cytokine production 677:703 In a follow-up to the main SATgenε study, we aimed to explore the effects of APOE genotype, as well as, dietary fat manipulation on ex vivo cytokine production. 24485322 3 23 from impact 520:525 arg1 response 535:542 this response 530:542 this response 530:542 Although dietary fat composition has been considered to modulate the inflammatory state in humans, very little is known about how APOE genotype can impact on this response. 24485322 5 24 theme dietary 954:960 arg1 periods 962:968 3.45g docosahexaenoic acid (DHA) dietary periods 921:968 3.45g docosahexaenoic acid (DHA) dietary periods (each diet eight weeks in duration assigned in the same order) 921:1031 Blood samples were collected from a subset of SATgenε participants (n=52/88), prospectively recruited according to APOE genotype (n=26 E3/E3 and n=26 E3/E4) after low-fat (LF), high saturated fat (HSF) and HSF with 3.45g docosahexaenoic acid (DHA) dietary periods (each diet eight weeks in duration assigned in the same order) for the measurement of ex vivo cytokine production using whole blood culture (WBC). 24485322 4 25 theme follow-up 550:558 arg1 study 580:584 a follow-up to the main SATgenε study 548:584 a follow-up to the main SATgenε study 548:584 In a follow-up to the main SATgenε study, we aimed to explore the effects of APOE genotype, as well as, dietary fat manipulation on ex vivo cytokine production. 24485322 5 26 theme Blood 706:710 arg1 samples 712:718 Blood samples 706:718 Blood samples 706:718 Blood samples were collected from a subset of SATgenε participants (n=52/88), prospectively recruited according to APOE genotype (n=26 E3/E3 and n=26 E3/E4) after low-fat (LF), high saturated fat (HSF) and HSF with 3.45g docosahexaenoic acid (DHA) dietary periods (each diet eight weeks in duration assigned in the same order) for the measurement of ex vivo cytokine production using whole blood culture (WBC). 24485322 6 27 with stimulation 1224:1234 arg1 LPS 1304:1306 LPS 1304:1306 LPS 1304:1306 Concentrations of IL-1beta, IL-6, IL-8, IL-10 and TNF-alpha were measured in WBC supernatant samples after stimulation for 24h with either 0.05 or 1μg/ml of bacterial lipopolysaccharide (LPS). 24485322 6 27 with stimulation 1224:1234 arg1 1μg/ml 1264:1269 1μg/ml 1264:1269 1μg/ml 1264:1269 Concentrations of IL-1beta, IL-6, IL-8, IL-10 and TNF-alpha were measured in WBC supernatant samples after stimulation for 24h with either 0.05 or 1μg/ml of bacterial lipopolysaccharide (LPS). 24485322 6 27 with stimulation 1224:1234 arg1 lipopolysaccharide 1284:1301 bacterial lipopolysaccharide 1274:1301 bacterial lipopolysaccharide (LPS) 1274:1307 Concentrations of IL-1beta, IL-6, IL-8, IL-10 and TNF-alpha were measured in WBC supernatant samples after stimulation for 24h with either 0.05 or 1μg/ml of bacterial lipopolysaccharide (LPS). 24485322 6 27 with stimulation 1224:1234 arg1 0.05 1256:1259 0.05 1256:1259 0.05 1256:1259 Concentrations of IL-1beta, IL-6, IL-8, IL-10 and TNF-alpha were measured in WBC supernatant samples after stimulation for 24h with either 0.05 or 1μg/ml of bacterial lipopolysaccharide (LPS). 24485322 8 28 theme WBC 1814:1816 arg1 samples 1818:1824 ex vivo LPS-stimulated WBC samples 1791:1824 ex vivo LPS-stimulated WBC samples obtained from normolipidaemic subjects 1791:1863 In conclusion, our study has revealed the amount and type of dietary fat can significantly modulate the production of TNF-α and IL-10 by ex vivo LPS-stimulated WBC samples obtained from normolipidaemic subjects. 24485322 4 29 theme manipulation 661:672 arg1 effects 611:617 the effects 607:617 the effects of APOE genotype, as well as, dietary fat manipulation on ex vivo cytokine production 607:703 In a follow-up to the main SATgenε study, we aimed to explore the effects of APOE genotype, as well as, dietary fat manipulation on ex vivo cytokine production. 24485322 0 30 theme Greater 0:6 arg1 impact 8:13 Greater impact 0:13 Greater impact of dietary fat manipulation than apolipoprotein E genotype on ex vivo cytokine production 0:103 Greater impact of dietary fat manipulation than apolipoprotein E genotype on ex vivo cytokine production - insights from the SATgenε study. 24485322 5 31 theme same 1021:1024 arg1 order 1026:1030 the same order 1017:1030 the same order 1017:1030 Blood samples were collected from a subset of SATgenε participants (n=52/88), prospectively recruited according to APOE genotype (n=26 E3/E3 and n=26 E3/E4) after low-fat (LF), high saturated fat (HSF) and HSF with 3.45g docosahexaenoic acid (DHA) dietary periods (each diet eight weeks in duration assigned in the same order) for the measurement of ex vivo cytokine production using whole blood culture (WBC). 24485322 8 32 dep amount 1696:1701 arg1 the 1692:1694 the 1692:1694 the 1692:1694 In conclusion, our study has revealed the amount and type of dietary fat can significantly modulate the production of TNF-α and IL-10 by ex vivo LPS-stimulated WBC samples obtained from normolipidaemic subjects. 24485322 4 33 theme ex 677:678 arg1 production 694:703 ex vivo cytokine production 677:703 ex vivo cytokine production 677:703 In a follow-up to the main SATgenε study, we aimed to explore the effects of APOE genotype, as well as, dietary fat manipulation on ex vivo cytokine production. 24485322 8 34 theme normolipidaemic 1840:1854 arg1 subjects 1856:1863 normolipidaemic subjects 1840:1863 normolipidaemic subjects 1840:1863 In conclusion, our study has revealed the amount and type of dietary fat can significantly modulate the production of TNF-α and IL-10 by ex vivo LPS-stimulated WBC samples obtained from normolipidaemic subjects. 24485322 0 35 theme fat 26:28 arg1 manipulation 30:41 dietary fat manipulation 18:41 dietary fat manipulation than apolipoprotein E genotype 18:72 Greater impact of dietary fat manipulation than apolipoprotein E genotype on ex vivo cytokine production - insights from the SATgenε study. 24485322 3 36 theme dietary 381:387 arg1 composition 393:403 dietary fat composition 381:403 dietary fat composition 381:403 Although dietary fat composition has been considered to modulate the inflammatory state in humans, very little is known about how APOE genotype can impact on this response. 24485322 0 37 theme E 63:63 arg1 genotype 65:72 apolipoprotein E genotype 48:72 apolipoprotein E genotype 48:72 Greater impact of dietary fat manipulation than apolipoprotein E genotype on ex vivo cytokine production - insights from the SATgenε study. 24485322 7 38 theme LF 1613:1614 arg1 diet 1616:1619 the LF diet 1609:1619 the LF diet 1609:1619 Cytokine levels were not influenced by genotype, whereas, dietary fat manipulation had a significant impact on TNF-α and IL-10 production; TNF-α concentration was higher after consumption of the HSF diet compared with baseline and the LF diet (P<0.05), whereas, IL-10 concentration was higher after the LF diet compared with baseline (P<0.05). 24485322 5 39 dep periods 962:968 arg1 weeks 987:991 each diet eight weeks 971:991 each diet eight weeks in duration assigned in the same order 971:1030 Blood samples were collected from a subset of SATgenε participants (n=52/88), prospectively recruited according to APOE genotype (n=26 E3/E3 and n=26 E3/E4) after low-fat (LF), high saturated fat (HSF) and HSF with 3.45g docosahexaenoic acid (DHA) dietary periods (each diet eight weeks in duration assigned in the same order) for the measurement of ex vivo cytokine production using whole blood culture (WBC). 24485322 7 40 theme Cytokine 1310:1317 arg1 levels 1319:1324 Cytokine levels 1310:1324 Cytokine levels 1310:1324 Cytokine levels were not influenced by genotype, whereas, dietary fat manipulation had a significant impact on TNF-α and IL-10 production; TNF-α concentration was higher after consumption of the HSF diet compared with baseline and the LF diet (P<0.05), whereas, IL-10 concentration was higher after the LF diet compared with baseline (P<0.05). 24485322 5 41 theme high 883:886 arg1 HSF 903:905 HSF 903:905 HSF 903:905 Blood samples were collected from a subset of SATgenε participants (n=52/88), prospectively recruited according to APOE genotype (n=26 E3/E3 and n=26 E3/E4) after low-fat (LF), high saturated fat (HSF) and HSF with 3.45g docosahexaenoic acid (DHA) dietary periods (each diet eight weeks in duration assigned in the same order) for the measurement of ex vivo cytokine production using whole blood culture (WBC). 24485322 5 41 theme high 883:886 arg1 fat 898:900 high saturated fat 883:900 high saturated fat (HSF) 883:906 Blood samples were collected from a subset of SATgenε participants (n=52/88), prospectively recruited according to APOE genotype (n=26 E3/E3 and n=26 E3/E4) after low-fat (LF), high saturated fat (HSF) and HSF with 3.45g docosahexaenoic acid (DHA) dietary periods (each diet eight weeks in duration assigned in the same order) for the measurement of ex vivo cytokine production using whole blood culture (WBC). 24485322 5 42 theme production 1073:1082 arg1 measurement 1041:1051 the measurement 1037:1051 the measurement of ex vivo cytokine production using whole blood culture (WBC) 1037:1114 Blood samples were collected from a subset of SATgenε participants (n=52/88), prospectively recruited according to APOE genotype (n=26 E3/E3 and n=26 E3/E4) after low-fat (LF), high saturated fat (HSF) and HSF with 3.45g docosahexaenoic acid (DHA) dietary periods (each diet eight weeks in duration assigned in the same order) for the measurement of ex vivo cytokine production using whole blood culture (WBC). 24485322 8 43 theme LPS-stimulated 1799:1812 arg1 samples 1818:1824 ex vivo LPS-stimulated WBC samples 1791:1824 ex vivo LPS-stimulated WBC samples obtained from normolipidaemic subjects 1791:1863 In conclusion, our study has revealed the amount and type of dietary fat can significantly modulate the production of TNF-α and IL-10 by ex vivo LPS-stimulated WBC samples obtained from normolipidaemic subjects. 24485322 6 44 theme WBC 1194:1196 arg1 samples 1210:1216 WBC supernatant samples 1194:1216 WBC supernatant samples 1194:1216 Concentrations of IL-1beta, IL-6, IL-8, IL-10 and TNF-alpha were measured in WBC supernatant samples after stimulation for 24h with either 0.05 or 1μg/ml of bacterial lipopolysaccharide (LPS). 24485322 6 45 theme bacterial 1274:1282 arg1 LPS 1304:1306 LPS 1304:1306 LPS 1304:1306 Concentrations of IL-1beta, IL-6, IL-8, IL-10 and TNF-alpha were measured in WBC supernatant samples after stimulation for 24h with either 0.05 or 1μg/ml of bacterial lipopolysaccharide (LPS). 24485322 6 45 theme bacterial 1274:1282 arg1 lipopolysaccharide 1284:1301 bacterial lipopolysaccharide 1274:1301 bacterial lipopolysaccharide (LPS) 1274:1307 Concentrations of IL-1beta, IL-6, IL-8, IL-10 and TNF-alpha were measured in WBC supernatant samples after stimulation for 24h with either 0.05 or 1μg/ml of bacterial lipopolysaccharide (LPS). 24485322 1 46 theme cardiovascular 214:227 arg1 risk 229:232 cardiovascular risk 214:232 cardiovascular risk 214:232 Apolipoprotein E (APOE) genotype is believed to play an important role in cardiovascular risk. 24485322 7 47 theme IL-10 1572:1576 arg1 concentration 1578:1590 IL-10 concentration 1572:1590 IL-10 concentration 1572:1590 Cytokine levels were not influenced by genotype, whereas, dietary fat manipulation had a significant impact on TNF-α and IL-10 production; TNF-α concentration was higher after consumption of the HSF diet compared with baseline and the LF diet (P<0.05), whereas, IL-10 concentration was higher after the LF diet compared with baseline (P<0.05). 24485322 5 48 theme APOE 821:824 arg1 genotype 826:833 APOE genotype 821:833 APOE genotype (n=26 E3/E3 and n=26 E3/E4) after low-fat (LF), high saturated fat (HSF) and HSF with 3.45g docosahexaenoic acid (DHA) dietary periods (each diet eight weeks in duration assigned in the same order) for the measurement of ex vivo cytokine production using whole blood culture (WBC) 821:1114 Blood samples were collected from a subset of SATgenε participants (n=52/88), prospectively recruited according to APOE genotype (n=26 E3/E3 and n=26 E3/E4) after low-fat (LF), high saturated fat (HSF) and HSF with 3.45g docosahexaenoic acid (DHA) dietary periods (each diet eight weeks in duration assigned in the same order) for the measurement of ex vivo cytokine production using whole blood culture (WBC). 24485322 0 49 from study 133:137 arg1 insights 107:114 insights 107:114 insights from the SATgenε study 107:137 Greater impact of dietary fat manipulation than apolipoprotein E genotype on ex vivo cytokine production - insights from the SATgenε study. 24485322 3 50 theme APOE 502:505 arg1 genotype 507:514 APOE genotype 502:514 APOE genotype 502:514 Although dietary fat composition has been considered to modulate the inflammatory state in humans, very little is known about how APOE genotype can impact on this response. 24485322 4 51 from effects 611:617 arg1 production 694:703 ex vivo cytokine production 677:703 ex vivo cytokine production 677:703 In a follow-up to the main SATgenε study, we aimed to explore the effects of APOE genotype, as well as, dietary fat manipulation on ex vivo cytokine production. 24485322 5 52 dep collected 725:733 arg1 recruited 798:806 recruited 798:806 recruited according to APOE genotype (n=26 E3/E3 and n=26 E3/E4) after low-fat (LF), high saturated fat (HSF) and HSF with 3.45g docosahexaenoic acid (DHA) dietary periods (each diet eight weeks in duration assigned in the same order) for the measurement of ex vivo cytokine production using whole blood culture (WBC) 798:1114 Blood samples were collected from a subset of SATgenε participants (n=52/88), prospectively recruited according to APOE genotype (n=26 E3/E3 and n=26 E3/E4) after low-fat (LF), high saturated fat (HSF) and HSF with 3.45g docosahexaenoic acid (DHA) dietary periods (each diet eight weeks in duration assigned in the same order) for the measurement of ex vivo cytokine production using whole blood culture (WBC). 24485322 2 53 theme lipid 289:293 arg1 levels 295:300 higher blood lipid levels 276:300 higher blood lipid levels 276:300 APOE4 carriers have been associated with higher blood lipid levels and a more pro-inflammatory state compared with APOE3/E3 individuals. 24485322 6 54 theme IL-10 1157:1161 arg1 Concentrations 1117:1130 Concentrations 1117:1130 Concentrations of IL-1beta, IL-6, IL-8, IL-10 and TNF-alpha 1117:1175 Concentrations of IL-1beta, IL-6, IL-8, IL-10 and TNF-alpha were measured in WBC supernatant samples after stimulation for 24h with either 0.05 or 1μg/ml of bacterial lipopolysaccharide (LPS). 24485322 2 55 theme higher 276:281 arg1 levels 295:300 higher blood lipid levels 276:300 higher blood lipid levels 276:300 APOE4 carriers have been associated with higher blood lipid levels and a more pro-inflammatory state compared with APOE3/E3 individuals. 24485322 7 56 theme IL-10 1431:1435 arg1 production 1437:1446 IL-10 production 1431:1446 IL-10 production 1431:1446 Cytokine levels were not influenced by genotype, whereas, dietary fat manipulation had a significant impact on TNF-α and IL-10 production; TNF-α concentration was higher after consumption of the HSF diet compared with baseline and the LF diet (P<0.05), whereas, IL-10 concentration was higher after the LF diet compared with baseline (P<0.05). 24485322 0 57 dep insights 107:114 arg1 impact 8:13 Greater impact 0:13 Greater impact of dietary fat manipulation than apolipoprotein E genotype on ex vivo cytokine production 0:103 Greater impact of dietary fat manipulation than apolipoprotein E genotype on ex vivo cytokine production - insights from the SATgenε study. 24485322 6 58 theme IL-8 1151:1154 arg1 Concentrations 1117:1130 Concentrations 1117:1130 Concentrations of IL-1beta, IL-6, IL-8, IL-10 and TNF-alpha 1117:1175 Concentrations of IL-1beta, IL-6, IL-8, IL-10 and TNF-alpha were measured in WBC supernatant samples after stimulation for 24h with either 0.05 or 1μg/ml of bacterial lipopolysaccharide (LPS). 24485322 5 59 with low-fat 869:875 arg1 periods 962:968 3.45g docosahexaenoic acid (DHA) dietary periods 921:968 3.45g docosahexaenoic acid (DHA) dietary periods (each diet eight weeks in duration assigned in the same order) 921:1031 Blood samples were collected from a subset of SATgenε participants (n=52/88), prospectively recruited according to APOE genotype (n=26 E3/E3 and n=26 E3/E4) after low-fat (LF), high saturated fat (HSF) and HSF with 3.45g docosahexaenoic acid (DHA) dietary periods (each diet eight weeks in duration assigned in the same order) for the measurement of ex vivo cytokine production using whole blood culture (WBC). 24485322 6 60 theme IL-6 1145:1148 arg1 Concentrations 1117:1130 Concentrations 1117:1130 Concentrations of IL-1beta, IL-6, IL-8, IL-10 and TNF-alpha 1117:1175 Concentrations of IL-1beta, IL-6, IL-8, IL-10 and TNF-alpha were measured in WBC supernatant samples after stimulation for 24h with either 0.05 or 1μg/ml of bacterial lipopolysaccharide (LPS). 24485322 4 61 dep ex 677:678 arg1 vivo 680:683 vivo 680:683 vivo 680:683 In a follow-up to the main SATgenε study, we aimed to explore the effects of APOE genotype, as well as, dietary fat manipulation on ex vivo cytokine production. 24485322 6 62 theme IL-1beta 1135:1142 arg1 Concentrations 1117:1130 Concentrations 1117:1130 Concentrations of IL-1beta, IL-6, IL-8, IL-10 and TNF-alpha 1117:1175 Concentrations of IL-1beta, IL-6, IL-8, IL-10 and TNF-alpha were measured in WBC supernatant samples after stimulation for 24h with either 0.05 or 1μg/ml of bacterial lipopolysaccharide (LPS). 24485322 2 63 theme APOE4 235:239 arg1 carriers 241:248 APOE4 carriers 235:248 APOE4 carriers 235:248 APOE4 carriers have been associated with higher blood lipid levels and a more pro-inflammatory state compared with APOE3/E3 individuals. 24485322 0 64 theme manipulation 30:41 arg1 impact 8:13 Greater impact 0:13 Greater impact of dietary fat manipulation than apolipoprotein E genotype on ex vivo cytokine production 0:103 Greater impact of dietary fat manipulation than apolipoprotein E genotype on ex vivo cytokine production - insights from the SATgenε study. 24485322 7 65 theme diet 1548:1551 arg1 consumption 1486:1496 consumption 1486:1496 consumption of the HSF diet compared with baseline and the LF diet (P<0.05) 1486:1560 Cytokine levels were not influenced by genotype, whereas, dietary fat manipulation had a significant impact on TNF-α and IL-10 production; TNF-α concentration was higher after consumption of the HSF diet compared with baseline and the LF diet (P<0.05), whereas, IL-10 concentration was higher after the LF diet compared with baseline (P<0.05). 24485322 8 66 theme dietary 1715:1721 arg1 fat 1723:1725 dietary fat 1715:1725 dietary fat 1715:1725 In conclusion, our study has revealed the amount and type of dietary fat can significantly modulate the production of TNF-α and IL-10 by ex vivo LPS-stimulated WBC samples obtained from normolipidaemic subjects. 24485322 5 67 theme docosahexaenoic 927:941 arg1 periods 962:968 3.45g docosahexaenoic acid (DHA) dietary periods 921:968 3.45g docosahexaenoic acid (DHA) dietary periods (each diet eight weeks in duration assigned in the same order) 921:1031 Blood samples were collected from a subset of SATgenε participants (n=52/88), prospectively recruited according to APOE genotype (n=26 E3/E3 and n=26 E3/E4) after low-fat (LF), high saturated fat (HSF) and HSF with 3.45g docosahexaenoic acid (DHA) dietary periods (each diet eight weeks in duration assigned in the same order) for the measurement of ex vivo cytokine production using whole blood culture (WBC). 24485322 4 68 theme APOE 622:625 arg1 genotype 627:634 APOE genotype 622:634 APOE genotype 622:634 In a follow-up to the main SATgenε study, we aimed to explore the effects of APOE genotype, as well as, dietary fat manipulation on ex vivo cytokine production. 24485322 5 69 theme whole 1090:1094 arg1 culture 1102:1108 whole blood culture 1090:1108 whole blood culture (WBC) 1090:1114 Blood samples were collected from a subset of SATgenε participants (n=52/88), prospectively recruited according to APOE genotype (n=26 E3/E3 and n=26 E3/E4) after low-fat (LF), high saturated fat (HSF) and HSF with 3.45g docosahexaenoic acid (DHA) dietary periods (each diet eight weeks in duration assigned in the same order) for the measurement of ex vivo cytokine production using whole blood culture (WBC). 24485322 5 69 theme whole 1090:1094 arg1 WBC 1111:1113 WBC 1111:1113 WBC 1111:1113 Blood samples were collected from a subset of SATgenε participants (n=52/88), prospectively recruited according to APOE genotype (n=26 E3/E3 and n=26 E3/E4) after low-fat (LF), high saturated fat (HSF) and HSF with 3.45g docosahexaenoic acid (DHA) dietary periods (each diet eight weeks in duration assigned in the same order) for the measurement of ex vivo cytokine production using whole blood culture (WBC). 24485322 0 70 theme ex 77:78 arg1 production 94:103 ex vivo cytokine production 77:103 ex vivo cytokine production 77:103 Greater impact of dietary fat manipulation than apolipoprotein E genotype on ex vivo cytokine production - insights from the SATgenε study. 24485322 1 71 theme Apolipoprotein 140:153 arg1 APOE 158:161 APOE 158:161 APOE 158:161 Apolipoprotein E (APOE) genotype is believed to play an important role in cardiovascular risk. 24485322 1 71 theme Apolipoprotein 140:153 arg1 E 155:155 Apolipoprotein E 140:155 Apolipoprotein E (APOE) genotype 140:171 Apolipoprotein E (APOE) genotype is believed to play an important role in cardiovascular risk. 24485322 7 72 theme dietary 1368:1374 arg1 manipulation 1380:1391 dietary fat manipulation 1368:1391 dietary fat manipulation 1368:1391 Cytokine levels were not influenced by genotype, whereas, dietary fat manipulation had a significant impact on TNF-α and IL-10 production; TNF-α concentration was higher after consumption of the HSF diet compared with baseline and the LF diet (P<0.05), whereas, IL-10 concentration was higher after the LF diet compared with baseline (P<0.05). 24485322 0 73 from impact 8:13 arg1 production 94:103 ex vivo cytokine production 77:103 ex vivo cytokine production 77:103 Greater impact of dietary fat manipulation than apolipoprotein E genotype on ex vivo cytokine production - insights from the SATgenε study. 24485322 0 74 theme cytokine 85:92 arg1 production 94:103 ex vivo cytokine production 77:103 ex vivo cytokine production 77:103 Greater impact of dietary fat manipulation than apolipoprotein E genotype on ex vivo cytokine production - insights from the SATgenε study. 24485322 6 75 theme TNF-alpha 1167:1175 arg1 Concentrations 1117:1130 Concentrations 1117:1130 Concentrations of IL-1beta, IL-6, IL-8, IL-10 and TNF-alpha 1117:1175 Concentrations of IL-1beta, IL-6, IL-8, IL-10 and TNF-alpha were measured in WBC supernatant samples after stimulation for 24h with either 0.05 or 1μg/ml of bacterial lipopolysaccharide (LPS). 24485322 7 76 theme HSF 1505:1507 arg1 diet 1509:1512 the HSF diet 1501:1512 the HSF diet compared with baseline 1501:1535 Cytokine levels were not influenced by genotype, whereas, dietary fat manipulation had a significant impact on TNF-α and IL-10 production; TNF-α concentration was higher after consumption of the HSF diet compared with baseline and the LF diet (P<0.05), whereas, IL-10 concentration was higher after the LF diet compared with baseline (P<0.05). 24485322 1 77 theme important 196:204 arg1 role 206:209 an important role 193:209 an important role 193:209 Apolipoprotein E (APOE) genotype is believed to play an important role in cardiovascular risk. 24485322 5 78 with HSF 912:914 arg1 periods 962:968 3.45g docosahexaenoic acid (DHA) dietary periods 921:968 3.45g docosahexaenoic acid (DHA) dietary periods (each diet eight weeks in duration assigned in the same order) 921:1031 Blood samples were collected from a subset of SATgenε participants (n=52/88), prospectively recruited according to APOE genotype (n=26 E3/E3 and n=26 E3/E4) after low-fat (LF), high saturated fat (HSF) and HSF with 3.45g docosahexaenoic acid (DHA) dietary periods (each diet eight weeks in duration assigned in the same order) for the measurement of ex vivo cytokine production using whole blood culture (WBC). 24485322 8 79 theme TNF-α 1772:1776 arg1 production 1758:1767 the production 1754:1767 the production of TNF-α and IL-10 by ex vivo LPS-stimulated WBC samples obtained from normolipidaemic subjects 1754:1863 In conclusion, our study has revealed the amount and type of dietary fat can significantly modulate the production of TNF-α and IL-10 by ex vivo LPS-stimulated WBC samples obtained from normolipidaemic subjects. 24485322 0 80 dep ex 77:78 arg1 vivo 80:83 vivo 80:83 vivo 80:83 Greater impact of dietary fat manipulation than apolipoprotein E genotype on ex vivo cytokine production - insights from the SATgenε study. 24485322 0 81 theme SATgenε 125:131 arg1 study 133:137 the SATgenε study 121:137 the SATgenε study 121:137 Greater impact of dietary fat manipulation than apolipoprotein E genotype on ex vivo cytokine production - insights from the SATgenε study. 24485322 5 82 dep genotype 826:833 arg1 E3/E3 841:845 n=26 E3/E3 and n=26 E3/E4 836:860 E3/E3 841:845 Blood samples were collected from a subset of SATgenε participants (n=52/88), prospectively recruited according to APOE genotype (n=26 E3/E3 and n=26 E3/E4) after low-fat (LF), high saturated fat (HSF) and HSF with 3.45g docosahexaenoic acid (DHA) dietary periods (each diet eight weeks in duration assigned in the same order) for the measurement of ex vivo cytokine production using whole blood culture (WBC). 24485322 5 82 dep genotype 826:833 arg1 E3/E4 856:860 n=26 E3/E3 and n=26 E3/E4 836:860 E3/E4 856:860 Blood samples were collected from a subset of SATgenε participants (n=52/88), prospectively recruited according to APOE genotype (n=26 E3/E3 and n=26 E3/E4) after low-fat (LF), high saturated fat (HSF) and HSF with 3.45g docosahexaenoic acid (DHA) dietary periods (each diet eight weeks in duration assigned in the same order) for the measurement of ex vivo cytokine production using whole blood culture (WBC). 24485322 2 83 theme APOE3/E3 350:357 arg1 individuals 359:369 APOE3/E3 individuals 350:369 APOE3/E3 individuals 350:369 APOE4 carriers have been associated with higher blood lipid levels and a more pro-inflammatory state compared with APOE3/E3 individuals. 24485322 0 84 theme dietary 18:24 arg1 manipulation 30:41 dietary fat manipulation 18:41 dietary fat manipulation than apolipoprotein E genotype 18:72 Greater impact of dietary fat manipulation than apolipoprotein E genotype on ex vivo cytokine production - insights from the SATgenε study. 24485322 5 85 from weeks 987:991 arg1 duration 996:1003 duration 996:1003 duration assigned in the same order 996:1030 Blood samples were collected from a subset of SATgenε participants (n=52/88), prospectively recruited according to APOE genotype (n=26 E3/E3 and n=26 E3/E4) after low-fat (LF), high saturated fat (HSF) and HSF with 3.45g docosahexaenoic acid (DHA) dietary periods (each diet eight weeks in duration assigned in the same order) for the measurement of ex vivo cytokine production using whole blood culture (WBC). 24485322 3 86 theme inflammatory 441:452 arg1 state 454:458 the inflammatory state 437:458 the inflammatory state in humans 437:468 Although dietary fat composition has been considered to modulate the inflammatory state in humans, very little is known about how APOE genotype can impact on this response. 24485322 0 87 theme apolipoprotein 48:61 arg1 genotype 65:72 apolipoprotein E genotype 48:72 apolipoprotein E genotype 48:72 Greater impact of dietary fat manipulation than apolipoprotein E genotype on ex vivo cytokine production - insights from the SATgenε study. 24485322 8 88 theme ex 1791:1792 arg1 samples 1818:1824 ex vivo LPS-stimulated WBC samples 1791:1824 ex vivo LPS-stimulated WBC samples obtained from normolipidaemic subjects 1791:1863 In conclusion, our study has revealed the amount and type of dietary fat can significantly modulate the production of TNF-α and IL-10 by ex vivo LPS-stimulated WBC samples obtained from normolipidaemic subjects. 24485322 3 89 theme fat 389:391 arg1 composition 393:403 dietary fat composition 381:403 dietary fat composition 381:403 Although dietary fat composition has been considered to modulate the inflammatory state in humans, very little is known about how APOE genotype can impact on this response. 24485322 3 90 from state 454:458 arg1 humans 463:468 humans 463:468 humans 463:468 Although dietary fat composition has been considered to modulate the inflammatory state in humans, very little is known about how APOE genotype can impact on this response. 24485322 4 91 dep manipulation 661:672 arg1 fat 657:659 dietary fat 649:659 dietary fat 649:659 In a follow-up to the main SATgenε study, we aimed to explore the effects of APOE genotype, as well as, dietary fat manipulation on ex vivo cytokine production. 24485322 7 92 contain had 1393:1395 arg2 impact 1411:1416 a significant impact 1397:1416 a significant impact 1397:1416 Cytokine levels were not influenced by genotype, whereas, dietary fat manipulation had a significant impact on TNF-α and IL-10 production; TNF-α concentration was higher after consumption of the HSF diet compared with baseline and the LF diet (P<0.05), whereas, IL-10 concentration was higher after the LF diet compared with baseline (P<0.05). 24485322 7 92 contain had 1393:1395 arg1 manipulation 1380:1391 dietary fat manipulation 1368:1391 dietary fat manipulation 1368:1391 Cytokine levels were not influenced by genotype, whereas, dietary fat manipulation had a significant impact on TNF-α and IL-10 production; TNF-α concentration was higher after consumption of the HSF diet compared with baseline and the LF diet (P<0.05), whereas, IL-10 concentration was higher after the LF diet compared with baseline (P<0.05). 24485322 4 93 theme main 567:570 arg1 SATgenε 572:578 the main SATgenε 563:578 the main SATgenε 563:578 In a follow-up to the main SATgenε study, we aimed to explore the effects of APOE genotype, as well as, dietary fat manipulation on ex vivo cytokine production. 24485322 5 94 theme cytokine 1064:1071 arg1 production 1073:1082 ex vivo cytokine production 1056:1082 ex vivo cytokine production using whole blood culture (WBC) 1056:1114 Blood samples were collected from a subset of SATgenε participants (n=52/88), prospectively recruited according to APOE genotype (n=26 E3/E3 and n=26 E3/E4) after low-fat (LF), high saturated fat (HSF) and HSF with 3.45g docosahexaenoic acid (DHA) dietary periods (each diet eight weeks in duration assigned in the same order) for the measurement of ex vivo cytokine production using whole blood culture (WBC). 24485322 5 95 theme saturated 888:896 arg1 HSF 903:905 HSF 903:905 HSF 903:905 Blood samples were collected from a subset of SATgenε participants (n=52/88), prospectively recruited according to APOE genotype (n=26 E3/E3 and n=26 E3/E4) after low-fat (LF), high saturated fat (HSF) and HSF with 3.45g docosahexaenoic acid (DHA) dietary periods (each diet eight weeks in duration assigned in the same order) for the measurement of ex vivo cytokine production using whole blood culture (WBC). 24485322 5 95 theme saturated 888:896 arg1 fat 898:900 high saturated fat 883:900 high saturated fat (HSF) 883:906 Blood samples were collected from a subset of SATgenε participants (n=52/88), prospectively recruited according to APOE genotype (n=26 E3/E3 and n=26 E3/E4) after low-fat (LF), high saturated fat (HSF) and HSF with 3.45g docosahexaenoic acid (DHA) dietary periods (each diet eight weeks in duration assigned in the same order) for the measurement of ex vivo cytokine production using whole blood culture (WBC). 24485322 5 96 with fat 898:900 arg1 periods 962:968 3.45g docosahexaenoic acid (DHA) dietary periods 921:968 3.45g docosahexaenoic acid (DHA) dietary periods (each diet eight weeks in duration assigned in the same order) 921:1031 Blood samples were collected from a subset of SATgenε participants (n=52/88), prospectively recruited according to APOE genotype (n=26 E3/E3 and n=26 E3/E4) after low-fat (LF), high saturated fat (HSF) and HSF with 3.45g docosahexaenoic acid (DHA) dietary periods (each diet eight weeks in duration assigned in the same order) for the measurement of ex vivo cytokine production using whole blood culture (WBC). 24485322 6 97 theme lipopolysaccharide 1284:1301 arg1 LPS 1304:1306 LPS 1304:1306 LPS 1304:1306 Concentrations of IL-1beta, IL-6, IL-8, IL-10 and TNF-alpha were measured in WBC supernatant samples after stimulation for 24h with either 0.05 or 1μg/ml of bacterial lipopolysaccharide (LPS). 24485322 6 97 theme lipopolysaccharide 1284:1301 arg1 lipopolysaccharide 1284:1301 bacterial lipopolysaccharide 1274:1301 bacterial lipopolysaccharide (LPS) 1274:1307 Concentrations of IL-1beta, IL-6, IL-8, IL-10 and TNF-alpha were measured in WBC supernatant samples after stimulation for 24h with either 0.05 or 1μg/ml of bacterial lipopolysaccharide (LPS). 24485322 6 97 theme lipopolysaccharide 1284:1301 arg1 0.05 1256:1259 0.05 1256:1259 0.05 1256:1259 Concentrations of IL-1beta, IL-6, IL-8, IL-10 and TNF-alpha were measured in WBC supernatant samples after stimulation for 24h with either 0.05 or 1μg/ml of bacterial lipopolysaccharide (LPS). 26909959 7 0 theme non-cellulosic 1075:1088 arg1 polysaccharides 1090:1104 non-cellulosic polysaccharides 1075:1104 non-cellulosic polysaccharides 1075:1104 These results suggest that GhUXS3 regulates the conversion of non-cellulosic polysaccharides and modulates their composition in plant cell walls. 26909959 1 1 theme biosynthetic 260:271 arg1 pathway 273:279 the non-cellulosic polysaccharide biosynthetic pathway 226:279 the non-cellulosic polysaccharide biosynthetic pathway 226:279 UDP-glucuronate decarboxylase (UDP-xylose synthase; UXS, EC 4.1.1.35) is an essential enzyme of the non-cellulosic polysaccharide biosynthetic pathway. 26909959 0 2 from expression 10:19 arg1 Arabidopsis 76:86 Arabidopsis 76:86 Arabidopsis 76:86 Antisense expression of Gossypium hirsutum UDP-glucuronate decarboxylase in Arabidopsis leads to changes in cell wall components. 26909959 2 3 theme UXS 375:377 arg1 protein 388:394 fluorescently labeled Gossypium hirsutum UXS (GhUXS3) protein 334:394 fluorescently labeled Gossypium hirsutum UXS (GhUXS3) protein 334:394 In the present study, using transient expression of fluorescently labeled Gossypium hirsutum UXS (GhUXS3) protein in onion epidermal cells, we observed that this protein was distributed in the cytoplasm. 26909959 1 4 theme pathway 273:279 arg1 decarboxylase 146:158 UDP-glucuronate decarboxylase 130:158 UDP-glucuronate decarboxylase (UDP-xylose synthase; UXS, EC 4.1.1.35) 130:198 UDP-glucuronate decarboxylase (UDP-xylose synthase; UXS, EC 4.1.1.35) is an essential enzyme of the non-cellulosic polysaccharide biosynthetic pathway. 26909959 1 4 theme pathway 273:279 arg1 enzyme 216:221 an essential enzyme 203:221 an essential enzyme of the non-cellulosic polysaccharide biosynthetic pathway 203:279 UDP-glucuronate decarboxylase (UDP-xylose synthase; UXS, EC 4.1.1.35) is an essential enzyme of the non-cellulosic polysaccharide biosynthetic pathway. 26909959 0 5 theme cell 108:111 arg1 components 118:127 cell wall components 108:127 cell wall components 108:127 Antisense expression of Gossypium hirsutum UDP-glucuronate decarboxylase in Arabidopsis leads to changes in cell wall components. 26909959 1 6 dep decarboxylase 146:158 arg1 synthase 172:179 UDP-xylose synthase 161:179 UDP-xylose synthase 161:179 UDP-glucuronate decarboxylase (UDP-xylose synthase; UXS, EC 4.1.1.35) is an essential enzyme of the non-cellulosic polysaccharide biosynthetic pathway. 26909959 2 7 from expression 320:329 arg1 cells 415:419 onion epidermal cells 399:419 onion epidermal cells 399:419 In the present study, using transient expression of fluorescently labeled Gossypium hirsutum UXS (GhUXS3) protein in onion epidermal cells, we observed that this protein was distributed in the cytoplasm. 26909959 7 8 from composition 1126:1136 arg1 walls 1152:1156 plant cell walls 1141:1156 plant cell walls 1141:1156 These results suggest that GhUXS3 regulates the conversion of non-cellulosic polysaccharides and modulates their composition in plant cell walls. 26909959 5 9 theme shorter 779:785 arg1 roots 787:791 shorter roots 779:791 shorter roots 779:791 Compared to the untransformed control, transgenic plant showed shorter roots, earlier blossom formation, and delayed senescence. 26909959 3 10 theme GhUXS3 490:495 arg1 cDNA 497:500 The GhUXS3 cDNA 486:500 The GhUXS3 cDNA of cotton 486:510 The GhUXS3 cDNA of cotton was expressed in an antisense orientation in Arabidopsis thaliana by Agrobacterium tumefaciens-mediated transformation. 26909959 6 11 theme Biochemical 845:855 arg1 analysis 857:864 Biochemical analysis 845:864 Biochemical analysis 845:864 Biochemical analysis indicated that levels of rhamnose, mannose, galactose, glucose, xylose, and cellulose were reduced in some of the down-regulated antisense plants. 26909959 2 12 theme present 289:295 arg1 study 297:301 the present study 285:301 the present study 285:301 In the present study, using transient expression of fluorescently labeled Gossypium hirsutum UXS (GhUXS3) protein in onion epidermal cells, we observed that this protein was distributed in the cytoplasm. 26909959 2 13 theme epidermal 405:413 arg1 cells 415:419 onion epidermal cells 399:419 onion epidermal cells 399:419 In the present study, using transient expression of fluorescently labeled Gossypium hirsutum UXS (GhUXS3) protein in onion epidermal cells, we observed that this protein was distributed in the cytoplasm. 26909959 0 14 theme wall 113:116 arg1 components 118:127 cell wall components 108:127 cell wall components 108:127 Antisense expression of Gossypium hirsutum UDP-glucuronate decarboxylase in Arabidopsis leads to changes in cell wall components. 26909959 2 15 theme onion 399:403 arg1 cells 415:419 onion epidermal cells 399:419 onion epidermal cells 399:419 In the present study, using transient expression of fluorescently labeled Gossypium hirsutum UXS (GhUXS3) protein in onion epidermal cells, we observed that this protein was distributed in the cytoplasm. 26909959 6 16 theme down-regulated 980:993 arg1 plants 1005:1010 the down-regulated antisense plants 976:1010 the down-regulated antisense plants 976:1010 Biochemical analysis indicated that levels of rhamnose, mannose, galactose, glucose, xylose, and cellulose were reduced in some of the down-regulated antisense plants. 26909959 7 17 theme plant 1141:1145 arg1 walls 1152:1156 plant cell walls 1141:1156 plant cell walls 1141:1156 These results suggest that GhUXS3 regulates the conversion of non-cellulosic polysaccharides and modulates their composition in plant cell walls. 26909959 8 18 theme cellular 1186:1193 arg1 function 1195:1202 a possible cellular function 1175:1202 a possible cellular function for GhUXS in determining the quality of cotton fibers 1175:1256 We also discuss a possible cellular function for GhUXS in determining the quality of cotton fibers. 26909959 0 19 theme Antisense 0:8 arg1 expression 10:19 Antisense expression 0:19 Antisense expression of Gossypium hirsutum UDP-glucuronate decarboxylase in Arabidopsis 0:86 Antisense expression of Gossypium hirsutum UDP-glucuronate decarboxylase in Arabidopsis leads to changes in cell wall components. 26909959 3 20 theme Arabidopsis 557:567 arg1 thaliana 569:576 Arabidopsis thaliana 557:576 Arabidopsis thaliana 557:576 The GhUXS3 cDNA of cotton was expressed in an antisense orientation in Arabidopsis thaliana by Agrobacterium tumefaciens-mediated transformation. 26909959 7 21 theme cell 1147:1150 arg1 walls 1152:1156 plant cell walls 1141:1156 plant cell walls 1141:1156 These results suggest that GhUXS3 regulates the conversion of non-cellulosic polysaccharides and modulates their composition in plant cell walls. 26909959 4 22 theme northern 700:707 arg1 blots 709:713 northern blots 700:713 northern blots 700:713 Homozygous plants showing down-regulation of UXS were analyzed with northern blots. 26909959 2 23 theme protein 388:394 arg1 expression 320:329 transient expression 310:329 transient expression of fluorescently labeled Gossypium hirsutum UXS (GhUXS3) protein in onion epidermal cells 310:419 In the present study, using transient expression of fluorescently labeled Gossypium hirsutum UXS (GhUXS3) protein in onion epidermal cells, we observed that this protein was distributed in the cytoplasm. 26909959 0 24 theme Gossypium 24:32 arg1 decarboxylase 59:71 Gossypium hirsutum UDP-glucuronate decarboxylase 24:71 Gossypium hirsutum UDP-glucuronate decarboxylase 24:71 Antisense expression of Gossypium hirsutum UDP-glucuronate decarboxylase in Arabidopsis leads to changes in cell wall components. 26909959 2 25 theme transient 310:318 arg1 expression 320:329 transient expression 310:329 transient expression of fluorescently labeled Gossypium hirsutum UXS (GhUXS3) protein in onion epidermal cells 310:419 In the present study, using transient expression of fluorescently labeled Gossypium hirsutum UXS (GhUXS3) protein in onion epidermal cells, we observed that this protein was distributed in the cytoplasm. 26909959 4 26 theme UXS 677:679 arg1 down-regulation 658:672 down-regulation 658:672 down-regulation of UXS 658:679 Homozygous plants showing down-regulation of UXS were analyzed with northern blots. 26909959 8 27 theme cotton 1244:1249 arg1 fibers 1251:1256 cotton fibers 1244:1256 cotton fibers 1244:1256 We also discuss a possible cellular function for GhUXS in determining the quality of cotton fibers. 26909959 6 28 theme antisense 995:1003 arg1 plants 1005:1010 the down-regulated antisense plants 976:1010 the down-regulated antisense plants 976:1010 Biochemical analysis indicated that levels of rhamnose, mannose, galactose, glucose, xylose, and cellulose were reduced in some of the down-regulated antisense plants. 26909959 0 29 from changes 97:103 arg1 components 118:127 cell wall components 108:127 cell wall components 108:127 Antisense expression of Gossypium hirsutum UDP-glucuronate decarboxylase in Arabidopsis leads to changes in cell wall components. 26909959 1 30 dep synthase 172:179 arg1 EC 187:188 EC 4.1.1.35 187:197 EC 4.1.1.35 187:197 UDP-glucuronate decarboxylase (UDP-xylose synthase; UXS, EC 4.1.1.35) is an essential enzyme of the non-cellulosic polysaccharide biosynthetic pathway. 26909959 1 30 dep synthase 172:179 arg1 UXS 182:184 UXS 182:184 UXS 182:184 UDP-glucuronate decarboxylase (UDP-xylose synthase; UXS, EC 4.1.1.35) is an essential enzyme of the non-cellulosic polysaccharide biosynthetic pathway. 26909959 0 31 theme UDP-glucuronate 43:57 arg1 decarboxylase 59:71 Gossypium hirsutum UDP-glucuronate decarboxylase 24:71 Gossypium hirsutum UDP-glucuronate decarboxylase 24:71 Antisense expression of Gossypium hirsutum UDP-glucuronate decarboxylase in Arabidopsis leads to changes in cell wall components. 26909959 2 32 theme Gossypium 356:364 arg1 protein 388:394 fluorescently labeled Gossypium hirsutum UXS (GhUXS3) protein 334:394 fluorescently labeled Gossypium hirsutum UXS (GhUXS3) protein 334:394 In the present study, using transient expression of fluorescently labeled Gossypium hirsutum UXS (GhUXS3) protein in onion epidermal cells, we observed that this protein was distributed in the cytoplasm. 26909959 5 33 theme transgenic 755:764 arg1 plant 766:770 transgenic plant 755:770 transgenic plant 755:770 Compared to the untransformed control, transgenic plant showed shorter roots, earlier blossom formation, and delayed senescence. 26909959 1 34 theme essential 206:214 arg1 decarboxylase 146:158 UDP-glucuronate decarboxylase 130:158 UDP-glucuronate decarboxylase (UDP-xylose synthase; UXS, EC 4.1.1.35) 130:198 UDP-glucuronate decarboxylase (UDP-xylose synthase; UXS, EC 4.1.1.35) is an essential enzyme of the non-cellulosic polysaccharide biosynthetic pathway. 26909959 1 34 theme essential 206:214 arg1 enzyme 216:221 an essential enzyme 203:221 an essential enzyme of the non-cellulosic polysaccharide biosynthetic pathway 203:279 UDP-glucuronate decarboxylase (UDP-xylose synthase; UXS, EC 4.1.1.35) is an essential enzyme of the non-cellulosic polysaccharide biosynthetic pathway. 26909959 0 35 theme hirsutum 34:41 arg1 decarboxylase 59:71 Gossypium hirsutum UDP-glucuronate decarboxylase 24:71 Gossypium hirsutum UDP-glucuronate decarboxylase 24:71 Antisense expression of Gossypium hirsutum UDP-glucuronate decarboxylase in Arabidopsis leads to changes in cell wall components. 26909959 5 36 theme delayed 825:831 arg1 senescence 833:842 delayed senescence 825:842 delayed senescence 825:842 Compared to the untransformed control, transgenic plant showed shorter roots, earlier blossom formation, and delayed senescence. 26909959 8 37 theme fibers 1251:1256 arg1 quality 1233:1239 the quality 1229:1239 the quality of cotton fibers 1229:1256 We also discuss a possible cellular function for GhUXS in determining the quality of cotton fibers. 26909959 7 38 theme polysaccharides 1090:1104 arg1 conversion 1061:1070 the conversion 1057:1070 the conversion of non-cellulosic polysaccharides 1057:1104 These results suggest that GhUXS3 regulates the conversion of non-cellulosic polysaccharides and modulates their composition in plant cell walls. 26909959 8 39 theme possible 1177:1184 arg1 function 1195:1202 a possible cellular function 1175:1202 a possible cellular function for GhUXS in determining the quality of cotton fibers 1175:1256 We also discuss a possible cellular function for GhUXS in determining the quality of cotton fibers. 26909959 3 40 theme Agrobacterium 581:593 arg1 transformation 616:629 Agrobacterium tumefaciens-mediated transformation 581:629 Agrobacterium tumefaciens-mediated transformation 581:629 The GhUXS3 cDNA of cotton was expressed in an antisense orientation in Arabidopsis thaliana by Agrobacterium tumefaciens-mediated transformation. 26909959 2 41 theme hirsutum 366:373 arg1 protein 388:394 fluorescently labeled Gossypium hirsutum UXS (GhUXS3) protein 334:394 fluorescently labeled Gossypium hirsutum UXS (GhUXS3) protein 334:394 In the present study, using transient expression of fluorescently labeled Gossypium hirsutum UXS (GhUXS3) protein in onion epidermal cells, we observed that this protein was distributed in the cytoplasm. 26909959 0 42 theme decarboxylase 59:71 arg1 expression 10:19 Antisense expression 0:19 Antisense expression of Gossypium hirsutum UDP-glucuronate decarboxylase in Arabidopsis 0:86 Antisense expression of Gossypium hirsutum UDP-glucuronate decarboxylase in Arabidopsis leads to changes in cell wall components. 26909959 3 43 theme tumefaciens-mediated 595:614 arg1 transformation 616:629 Agrobacterium tumefaciens-mediated transformation 581:629 Agrobacterium tumefaciens-mediated transformation 581:629 The GhUXS3 cDNA of cotton was expressed in an antisense orientation in Arabidopsis thaliana by Agrobacterium tumefaciens-mediated transformation. 26909959 3 44 theme cotton 505:510 arg1 cDNA 497:500 The GhUXS3 cDNA 486:500 The GhUXS3 cDNA of cotton 486:510 The GhUXS3 cDNA of cotton was expressed in an antisense orientation in Arabidopsis thaliana by Agrobacterium tumefaciens-mediated transformation. 26909959 1 45 theme UDP-glucuronate 130:144 arg1 decarboxylase 146:158 UDP-glucuronate decarboxylase 130:158 UDP-glucuronate decarboxylase (UDP-xylose synthase; UXS, EC 4.1.1.35) 130:198 UDP-glucuronate decarboxylase (UDP-xylose synthase; UXS, EC 4.1.1.35) is an essential enzyme of the non-cellulosic polysaccharide biosynthetic pathway. 26909959 1 45 theme UDP-glucuronate 130:144 arg1 enzyme 216:221 an essential enzyme 203:221 an essential enzyme of the non-cellulosic polysaccharide biosynthetic pathway 203:279 UDP-glucuronate decarboxylase (UDP-xylose synthase; UXS, EC 4.1.1.35) is an essential enzyme of the non-cellulosic polysaccharide biosynthetic pathway. 26909959 6 46 theme rhamnose 891:898 arg1 levels 881:886 levels 881:886 levels of rhamnose, mannose, galactose, glucose, xylose, and cellulose 881:950 Biochemical analysis indicated that levels of rhamnose, mannose, galactose, glucose, xylose, and cellulose were reduced in some of the down-regulated antisense plants. 26909959 2 47 theme labeled 348:354 arg1 protein 388:394 fluorescently labeled Gossypium hirsutum UXS (GhUXS3) protein 334:394 fluorescently labeled Gossypium hirsutum UXS (GhUXS3) protein 334:394 In the present study, using transient expression of fluorescently labeled Gossypium hirsutum UXS (GhUXS3) protein in onion epidermal cells, we observed that this protein was distributed in the cytoplasm. 26909959 5 48 theme untransformed 732:744 arg1 control 746:752 the untransformed control 728:752 the untransformed control 728:752 Compared to the untransformed control, transgenic plant showed shorter roots, earlier blossom formation, and delayed senescence. 26909959 3 49 theme antisense 532:540 arg1 orientation 542:552 an antisense orientation 529:552 an antisense orientation in Arabidopsis thaliana 529:576 The GhUXS3 cDNA of cotton was expressed in an antisense orientation in Arabidopsis thaliana by Agrobacterium tumefaciens-mediated transformation. 26909959 4 50 theme Homozygous 632:641 arg1 plants 643:648 Homozygous plants 632:648 Homozygous plants showing down-regulation of UXS 632:679 Homozygous plants showing down-regulation of UXS were analyzed with northern blots. 26909959 5 51 theme earlier 794:800 arg1 formation 810:818 earlier blossom formation 794:818 earlier blossom formation 794:818 Compared to the untransformed control, transgenic plant showed shorter roots, earlier blossom formation, and delayed senescence. 26909959 3 52 from orientation 542:552 arg1 thaliana 569:576 Arabidopsis thaliana 557:576 Arabidopsis thaliana 557:576 The GhUXS3 cDNA of cotton was expressed in an antisense orientation in Arabidopsis thaliana by Agrobacterium tumefaciens-mediated transformation. 26909959 1 53 theme UDP-xylose 161:170 arg1 synthase 172:179 UDP-xylose synthase 161:179 UDP-xylose synthase 161:179 UDP-glucuronate decarboxylase (UDP-xylose synthase; UXS, EC 4.1.1.35) is an essential enzyme of the non-cellulosic polysaccharide biosynthetic pathway. 26909959 1 54 theme non-cellulosic 230:243 arg1 pathway 273:279 the non-cellulosic polysaccharide biosynthetic pathway 226:279 the non-cellulosic polysaccharide biosynthetic pathway 226:279 UDP-glucuronate decarboxylase (UDP-xylose synthase; UXS, EC 4.1.1.35) is an essential enzyme of the non-cellulosic polysaccharide biosynthetic pathway. 26909959 5 55 theme blossom 802:808 arg1 formation 810:818 earlier blossom formation 794:818 earlier blossom formation 794:818 Compared to the untransformed control, transgenic plant showed shorter roots, earlier blossom formation, and delayed senescence. 26909959 2 56 theme GhUXS3 380:385 arg1 protein 388:394 fluorescently labeled Gossypium hirsutum UXS (GhUXS3) protein 334:394 fluorescently labeled Gossypium hirsutum UXS (GhUXS3) protein 334:394 In the present study, using transient expression of fluorescently labeled Gossypium hirsutum UXS (GhUXS3) protein in onion epidermal cells, we observed that this protein was distributed in the cytoplasm. 26909959 1 57 theme polysaccharide 245:258 arg1 pathway 273:279 the non-cellulosic polysaccharide biosynthetic pathway 226:279 the non-cellulosic polysaccharide biosynthetic pathway 226:279 UDP-glucuronate decarboxylase (UDP-xylose synthase; UXS, EC 4.1.1.35) is an essential enzyme of the non-cellulosic polysaccharide biosynthetic pathway. 26725456 7 0 theme sequencing-based 1032:1047 arg1 methods 1049:1055 Culture-independent and sequencing-based methods 1008:1055 Culture-independent and sequencing-based methods 1008:1055 Culture-independent and sequencing-based methods were used to analyse caecal microbial composition. 26725456 11 1 theme gut 1778:1780 arg1 microbiota 1782:1791 the gut microbiota 1774:1791 the gut microbiota 1774:1791 SIGNIFICANCE AND IMPACT OF THE STUDY The novelty of this study lies to the beneficial effect of palygorskite (a clay mineral) to pullets growth and health, likely through modulation of the gut microbiota. 26725456 1 2 theme inclusion 242:250 arg1 effect 208:213 the effect 204:213 the effect of early-posthatch dietary inclusion of the clay mineral palygorskite on laying pullets' growth 204:309 AIMS The objective of this study was twofold: (i) to examine the effect of early-posthatch dietary inclusion of the clay mineral palygorskite on laying pullets' growth and (ii) to determine the potential effects of the latter diet on caecal microbial communities. 26725456 7 3 theme Culture-independent 1008:1026 arg1 methods 1049:1055 Culture-independent and sequencing-based methods 1008:1055 Culture-independent and sequencing-based methods 1008:1055 Culture-independent and sequencing-based methods were used to analyse caecal microbial composition. 26725456 2 4 dep allocated 521:529 arg1 % 599:599 0 and 0·5% 590:599 0 and 0·5% palygorskite respectively 590:625 METHODS AND RESULTS Four hundred and thirty-two female, 1-day-old Hyline Brown chickens were equally and randomly allocated to two dietary treatment groups; control and palygorskite (0 and 0·5% palygorskite respectively). 26725456 5 5 theme period 783:788 arg1 end 764:766 the end 760:766 the end of the rearing period 760:788 At the end of the rearing period, 53 birds per group were transferred to laying cages without any changes in their respective dietary treatments. 26725456 10 6 from efficient 1555:1563 arg1 production 1577:1586 butyrate production 1568:1586 butyrate production 1568:1586 Moreover, in the caeca of the former pullets a more favourable microbiota was evident; it comprised largely of bacteria that are major degraders of resistant polysaccharides and efficient in butyrate production. 26725456 8 7 theme group 1198:1202 arg1 uniformity 1171:1180 the uniformity 1167:1180 the uniformity of the relative group at the end of the rearing period 1167:1235 CONCLUSIONS Palygorskite dietary supplementation increased the uniformity of the relative group at the end of the rearing period. 26725456 8 8 theme dietary 1133:1139 arg1 supplementation 1141:1155 Palygorskite dietary supplementation 1120:1155 Palygorskite dietary supplementation 1120:1155 CONCLUSIONS Palygorskite dietary supplementation increased the uniformity of the relative group at the end of the rearing period. 26725456 10 9 theme major 1506:1510 arg1 bacteria 1488:1495 bacteria 1488:1495 bacteria that are major degraders of resistant polysaccharides and efficient in butyrate production 1488:1586 Moreover, in the caeca of the former pullets a more favourable microbiota was evident; it comprised largely of bacteria that are major degraders of resistant polysaccharides and efficient in butyrate production. 26725456 10 9 theme major 1506:1510 arg1 degraders 1512:1520 major degraders 1506:1520 major degraders of resistant polysaccharides 1506:1549 Moreover, in the caeca of the former pullets a more favourable microbiota was evident; it comprised largely of bacteria that are major degraders of resistant polysaccharides and efficient in butyrate production. 26725456 11 10 theme mineral 1706:1712 arg1 palygorskite 1685:1696 palygorskite 1685:1696 palygorskite (a clay mineral) 1685:1713 SIGNIFICANCE AND IMPACT OF THE STUDY The novelty of this study lies to the beneficial effect of palygorskite (a clay mineral) to pullets growth and health, likely through modulation of the gut microbiota. 26725456 11 10 theme mineral 1706:1712 arg1 clay 1701:1704 a clay mineral 1699:1712 a clay mineral 1699:1712 SIGNIFICANCE AND IMPACT OF THE STUDY The novelty of this study lies to the beneficial effect of palygorskite (a clay mineral) to pullets growth and health, likely through modulation of the gut microbiota. 26725456 2 11 theme treatment 546:554 arg1 control 564:570 control 564:570 control 564:570 METHODS AND RESULTS Four hundred and thirty-two female, 1-day-old Hyline Brown chickens were equally and randomly allocated to two dietary treatment groups; control and palygorskite (0 and 0·5% palygorskite respectively). 26725456 2 11 theme treatment 546:554 arg1 groups 556:561 two dietary treatment groups 534:561 two dietary treatment groups; control and palygorskite 534:587 METHODS AND RESULTS Four hundred and thirty-two female, 1-day-old Hyline Brown chickens were equally and randomly allocated to two dietary treatment groups; control and palygorskite (0 and 0·5% palygorskite respectively). 26725456 2 11 theme treatment 546:554 arg1 palygorskite 576:587 palygorskite 576:587 palygorskite 576:587 METHODS AND RESULTS Four hundred and thirty-two female, 1-day-old Hyline Brown chickens were equally and randomly allocated to two dietary treatment groups; control and palygorskite (0 and 0·5% palygorskite respectively). 26725456 9 12 theme different 1277:1285 arg1 profiles 1325:1332 different and more homogeneous caecal microbial profiles 1277:1332 different and more homogeneous caecal microbial profiles 1277:1332 Pullets that received palygorskite had different and more homogeneous caecal microbial profiles at onset of lay when compared to controls. 26725456 8 13 theme rearing 1222:1228 arg1 period 1230:1235 the rearing period 1218:1235 the rearing period 1218:1235 CONCLUSIONS Palygorskite dietary supplementation increased the uniformity of the relative group at the end of the rearing period. 26725456 10 14 theme polysaccharides 1535:1549 arg1 bacteria 1488:1495 bacteria 1488:1495 bacteria that are major degraders of resistant polysaccharides and efficient in butyrate production 1488:1586 Moreover, in the caeca of the former pullets a more favourable microbiota was evident; it comprised largely of bacteria that are major degraders of resistant polysaccharides and efficient in butyrate production. 26725456 10 14 theme polysaccharides 1535:1549 arg1 degraders 1512:1520 major degraders 1506:1520 major degraders of resistant polysaccharides 1506:1549 Moreover, in the caeca of the former pullets a more favourable microbiota was evident; it comprised largely of bacteria that are major degraders of resistant polysaccharides and efficient in butyrate production. 26725456 1 15 theme diet 369:372 arg1 effects 347:353 the potential effects 333:353 the potential effects of the latter diet on caecal microbial communities 333:404 AIMS The objective of this study was twofold: (i) to examine the effect of early-posthatch dietary inclusion of the clay mineral palygorskite on laying pullets' growth and (ii) to determine the potential effects of the latter diet on caecal microbial communities. 26725456 1 16 theme caecal 377:382 arg1 communities 394:404 caecal microbial communities 377:404 caecal microbial communities 377:404 AIMS The objective of this study was twofold: (i) to examine the effect of early-posthatch dietary inclusion of the clay mineral palygorskite on laying pullets' growth and (ii) to determine the potential effects of the latter diet on caecal microbial communities. 26725456 2 17 theme 1-day-old 463:471 arg1 chickens 486:493 1-day-old Hyline Brown chickens 463:493 1-day-old Hyline Brown chickens 463:493 METHODS AND RESULTS Four hundred and thirty-two female, 1-day-old Hyline Brown chickens were equally and randomly allocated to two dietary treatment groups; control and palygorskite (0 and 0·5% palygorskite respectively). 26725456 2 17 theme 1-day-old 463:471 arg1 female 455:460 female 455:460 female 455:460 METHODS AND RESULTS Four hundred and thirty-two female, 1-day-old Hyline Brown chickens were equally and randomly allocated to two dietary treatment groups; control and palygorskite (0 and 0·5% palygorskite respectively). 26725456 6 18 theme lay 915:917 arg1 onset 906:910 onset 906:910 onset of lay 906:917 At onset of lay, eight birds from each group were euthanized and their caeca were obtained for analysis. 26725456 1 19 theme study 170:174 arg1 twofold 180:186 twofold 180:186 twofold 180:186 AIMS The objective of this study was twofold: (i) to examine the effect of early-posthatch dietary inclusion of the clay mineral palygorskite on laying pullets' growth and (ii) to determine the potential effects of the latter diet on caecal microbial communities. 26725456 1 19 theme study 170:174 arg1 objective 152:160 The objective 148:160 The objective of this study 148:174 AIMS The objective of this study was twofold: (i) to examine the effect of early-posthatch dietary inclusion of the clay mineral palygorskite on laying pullets' growth and (ii) to determine the potential effects of the latter diet on caecal microbial communities. 26725456 2 20 theme palygorskite 601:612 arg1 % 599:599 0 and 0·5% 590:599 0 and 0·5% palygorskite respectively 590:625 METHODS AND RESULTS Four hundred and thirty-two female, 1-day-old Hyline Brown chickens were equally and randomly allocated to two dietary treatment groups; control and palygorskite (0 and 0·5% palygorskite respectively). 26725456 1 21 dep AIMS 143:146 arg1 determine 323:331 determine 323:331 to determine the potential effects of the latter diet on caecal microbial communities 320:404 AIMS The objective of this study was twofold: (i) to examine the effect of early-posthatch dietary inclusion of the clay mineral palygorskite on laying pullets' growth and (ii) to determine the potential effects of the latter diet on caecal microbial communities. 26725456 1 21 dep AIMS 143:146 arg1 twofold 180:186 twofold 180:186 twofold 180:186 AIMS The objective of this study was twofold: (i) to examine the effect of early-posthatch dietary inclusion of the clay mineral palygorskite on laying pullets' growth and (ii) to determine the potential effects of the latter diet on caecal microbial communities. 26725456 1 21 dep AIMS 143:146 arg1 objective 152:160 The objective 148:160 The objective of this study 148:174 AIMS The objective of this study was twofold: (i) to examine the effect of early-posthatch dietary inclusion of the clay mineral palygorskite on laying pullets' growth and (ii) to determine the potential effects of the latter diet on caecal microbial communities. 26725456 1 21 dep AIMS 143:146 arg1 examine 196:202 examine 196:202 to examine the effect of early-posthatch dietary inclusion of the clay mineral palygorskite on laying pullets' growth 193:309 AIMS The objective of this study was twofold: (i) to examine the effect of early-posthatch dietary inclusion of the clay mineral palygorskite on laying pullets' growth and (ii) to determine the potential effects of the latter diet on caecal microbial communities. 26725456 11 22 theme palygorskite 1685:1696 arg1 effect 1675:1680 the beneficial effect 1660:1680 the beneficial effect of palygorskite (a clay mineral) to pullets growth and health 1660:1742 SIGNIFICANCE AND IMPACT OF THE STUDY The novelty of this study lies to the beneficial effect of palygorskite (a clay mineral) to pullets growth and health, likely through modulation of the gut microbiota. 26725456 0 23 theme caecal 106:111 arg1 microbiota 113:122 caecal microbiota 106:122 caecal microbiota in laying pullets 106:140 Dietary supplementation with the clay mineral palygorskite affects performance and beneficially modulates caecal microbiota in laying pullets. 26725456 5 24 theme respective 872:881 arg1 treatments 891:900 their respective dietary treatments 866:900 their respective dietary treatments 866:900 At the end of the rearing period, 53 birds per group were transferred to laying cages without any changes in their respective dietary treatments. 26725456 2 25 theme Brown 480:484 arg1 chickens 486:493 1-day-old Hyline Brown chickens 463:493 1-day-old Hyline Brown chickens 463:493 METHODS AND RESULTS Four hundred and thirty-two female, 1-day-old Hyline Brown chickens were equally and randomly allocated to two dietary treatment groups; control and palygorskite (0 and 0·5% palygorskite respectively). 26725456 2 25 theme Brown 480:484 arg1 female 455:460 female 455:460 female 455:460 METHODS AND RESULTS Four hundred and thirty-two female, 1-day-old Hyline Brown chickens were equally and randomly allocated to two dietary treatment groups; control and palygorskite (0 and 0·5% palygorskite respectively). 26725456 4 26 theme body 710:713 arg1 gain 722:725 body weight gain 710:725 body weight gain 710:725 Feed intake, feed conversion ratio, body weight gain and uniformity were assessed. 26725456 0 27 theme Dietary 0:6 arg1 supplementation 8:22 Dietary supplementation 0:22 Dietary supplementation with the clay mineral palygorskite 0:57 Dietary supplementation with the clay mineral palygorskite affects performance and beneficially modulates caecal microbiota in laying pullets. 26725456 1 28 theme clay 259:262 arg1 palygorskite 272:283 the clay mineral palygorskite 255:283 the clay mineral palygorskite 255:283 AIMS The objective of this study was twofold: (i) to examine the effect of early-posthatch dietary inclusion of the clay mineral palygorskite on laying pullets' growth and (ii) to determine the potential effects of the latter diet on caecal microbial communities. 26725456 2 29 dep METHODS 407:413 arg1 allocated 521:529 allocated 521:529 were equally and randomly allocated to two dietary treatment groups; control and palygorskite (0 and 0·5% palygorskite respectively) 495:626 METHODS AND RESULTS Four hundred and thirty-two female, 1-day-old Hyline Brown chickens were equally and randomly allocated to two dietary treatment groups; control and palygorskite (0 and 0·5% palygorskite respectively). 26725456 4 30 theme feed 687:690 arg1 ratio 703:707 feed conversion ratio 687:707 feed conversion ratio 687:707 Feed intake, feed conversion ratio, body weight gain and uniformity were assessed. 26725456 7 31 theme caecal 1078:1083 arg1 composition 1095:1105 caecal microbial composition 1078:1105 caecal microbial composition 1078:1105 Culture-independent and sequencing-based methods were used to analyse caecal microbial composition. 26725456 1 32 theme palygorskite 272:283 arg1 inclusion 242:250 early-posthatch dietary inclusion 218:250 early-posthatch dietary inclusion of the clay mineral palygorskite 218:283 AIMS The objective of this study was twofold: (i) to examine the effect of early-posthatch dietary inclusion of the clay mineral palygorskite on laying pullets' growth and (ii) to determine the potential effects of the latter diet on caecal microbial communities. 26725456 10 33 theme pullets 1414:1420 arg1 caeca 1394:1398 the caeca 1390:1398 the caeca of the former pullets 1390:1420 Moreover, in the caeca of the former pullets a more favourable microbiota was evident; it comprised largely of bacteria that are major degraders of resistant polysaccharides and efficient in butyrate production. 26725456 0 34 theme clay 33:36 arg1 palygorskite 46:57 the clay mineral palygorskite 29:57 the clay mineral palygorskite 29:57 Dietary supplementation with the clay mineral palygorskite affects performance and beneficially modulates caecal microbiota in laying pullets. 26725456 1 35 theme laying 288:293 arg1 growth 304:309 laying pullets' growth 288:309 laying pullets' growth 288:309 AIMS The objective of this study was twofold: (i) to examine the effect of early-posthatch dietary inclusion of the clay mineral palygorskite on laying pullets' growth and (ii) to determine the potential effects of the latter diet on caecal microbial communities. 26725456 10 36 from production 1577:1586 arg1 efficient 1555:1563 efficient 1555:1563 efficient 1555:1563 Moreover, in the caeca of the former pullets a more favourable microbiota was evident; it comprised largely of bacteria that are major degraders of resistant polysaccharides and efficient in butyrate production. 26725456 9 37 theme homogeneous 1296:1306 arg1 profiles 1325:1332 different and more homogeneous caecal microbial profiles 1277:1332 different and more homogeneous caecal microbial profiles 1277:1332 Pullets that received palygorskite had different and more homogeneous caecal microbial profiles at onset of lay when compared to controls. 26725456 9 38 theme microbial 1315:1323 arg1 profiles 1325:1332 different and more homogeneous caecal microbial profiles 1277:1332 different and more homogeneous caecal microbial profiles 1277:1332 Pullets that received palygorskite had different and more homogeneous caecal microbial profiles at onset of lay when compared to controls. 26725456 1 39 dep determine 323:331 arg1 ii 316:317 ii 316:317 ii 316:317 AIMS The objective of this study was twofold: (i) to examine the effect of early-posthatch dietary inclusion of the clay mineral palygorskite on laying pullets' growth and (ii) to determine the potential effects of the latter diet on caecal microbial communities. 26725456 8 40 dep CONCLUSIONS 1108:1118 arg1 increased 1157:1165 increased 1157:1165 increased the uniformity of the relative group at the end of the rearing period 1157:1235 CONCLUSIONS Palygorskite dietary supplementation increased the uniformity of the relative group at the end of the rearing period. 26725456 9 41 contain had 1273:1275 arg2 profiles 1325:1332 different and more homogeneous caecal microbial profiles 1277:1332 different and more homogeneous caecal microbial profiles 1277:1332 Pullets that received palygorskite had different and more homogeneous caecal microbial profiles at onset of lay when compared to controls. 26725456 9 41 contain had 1273:1275 arg1 Pullets 1238:1244 Pullets 1238:1244 Pullets that received palygorskite 1238:1271 Pullets that received palygorskite had different and more homogeneous caecal microbial profiles at onset of lay when compared to controls. 26725456 7 42 used used 1062:1065 arg2 methods 1049:1055 Culture-independent and sequencing-based methods 1008:1055 Culture-independent and sequencing-based methods 1008:1055 Culture-independent and sequencing-based methods were used to analyse caecal microbial composition. 26725456 11 43 theme study 1646:1650 arg1 novelty 1630:1636 The novelty 1626:1636 SIGNIFICANCE AND IMPACT OF THE STUDY The novelty of this study 1589:1650 SIGNIFICANCE AND IMPACT OF THE STUDY The novelty of this study lies to the beneficial effect of palygorskite (a clay mineral) to pullets growth and health, likely through modulation of the gut microbiota. 26725456 11 44 theme microbiota 1782:1791 arg1 modulation 1760:1769 modulation 1760:1769 modulation of the gut microbiota 1760:1791 SIGNIFICANCE AND IMPACT OF THE STUDY The novelty of this study lies to the beneficial effect of palygorskite (a clay mineral) to pullets growth and health, likely through modulation of the gut microbiota. 26725456 1 45 theme dietary 234:240 arg1 inclusion 242:250 early-posthatch dietary inclusion 218:250 early-posthatch dietary inclusion of the clay mineral palygorskite 218:283 AIMS The objective of this study was twofold: (i) to examine the effect of early-posthatch dietary inclusion of the clay mineral palygorskite on laying pullets' growth and (ii) to determine the potential effects of the latter diet on caecal microbial communities. 26725456 5 46 theme rearing 775:781 arg1 period 783:788 the rearing period 771:788 the rearing period 771:788 At the end of the rearing period, 53 birds per group were transferred to laying cages without any changes in their respective dietary treatments. 26725456 10 47 theme resistant 1525:1533 arg1 polysaccharides 1535:1549 resistant polysaccharides 1525:1549 resistant polysaccharides 1525:1549 Moreover, in the caeca of the former pullets a more favourable microbiota was evident; it comprised largely of bacteria that are major degraders of resistant polysaccharides and efficient in butyrate production. 26725456 8 48 theme relative 1189:1196 arg1 group 1198:1202 the relative group 1185:1202 the relative group 1185:1202 CONCLUSIONS Palygorskite dietary supplementation increased the uniformity of the relative group at the end of the rearing period. 26725456 6 49 from group 942:946 arg1 birds 926:930 eight birds 920:930 eight birds from each group 920:946 At onset of lay, eight birds from each group were euthanized and their caeca were obtained for analysis. 26725456 8 50 theme Palygorskite 1120:1131 arg1 supplementation 1141:1155 Palygorskite dietary supplementation 1120:1155 Palygorskite dietary supplementation 1120:1155 CONCLUSIONS Palygorskite dietary supplementation increased the uniformity of the relative group at the end of the rearing period. 26725456 2 51 dep groups 556:561 arg1 control 564:570 control 564:570 control 564:570 METHODS AND RESULTS Four hundred and thirty-two female, 1-day-old Hyline Brown chickens were equally and randomly allocated to two dietary treatment groups; control and palygorskite (0 and 0·5% palygorskite respectively). 26725456 2 51 dep groups 556:561 arg1 groups 556:561 two dietary treatment groups 534:561 two dietary treatment groups; control and palygorskite 534:587 METHODS AND RESULTS Four hundred and thirty-two female, 1-day-old Hyline Brown chickens were equally and randomly allocated to two dietary treatment groups; control and palygorskite (0 and 0·5% palygorskite respectively). 26725456 2 51 dep groups 556:561 arg1 palygorskite 576:587 palygorskite 576:587 palygorskite 576:587 METHODS AND RESULTS Four hundred and thirty-two female, 1-day-old Hyline Brown chickens were equally and randomly allocated to two dietary treatment groups; control and palygorskite (0 and 0·5% palygorskite respectively). 26725456 10 52 from caeca 1394:1398 arg1 microbiota 1440:1449 a more favourable microbiota 1422:1449 a more favourable microbiota 1422:1449 Moreover, in the caeca of the former pullets a more favourable microbiota was evident; it comprised largely of bacteria that are major degraders of resistant polysaccharides and efficient in butyrate production. 26725456 10 52 from caeca 1394:1398 arg1 evident 1455:1461 evident 1455:1461 evident 1455:1461 Moreover, in the caeca of the former pullets a more favourable microbiota was evident; it comprised largely of bacteria that are major degraders of resistant polysaccharides and efficient in butyrate production. 26725456 1 53 theme latter 362:367 arg1 diet 369:372 the latter diet 358:372 the latter diet 358:372 AIMS The objective of this study was twofold: (i) to examine the effect of early-posthatch dietary inclusion of the clay mineral palygorskite on laying pullets' growth and (ii) to determine the potential effects of the latter diet on caecal microbial communities. 26725456 2 54 theme dietary 538:544 arg1 control 564:570 control 564:570 control 564:570 METHODS AND RESULTS Four hundred and thirty-two female, 1-day-old Hyline Brown chickens were equally and randomly allocated to two dietary treatment groups; control and palygorskite (0 and 0·5% palygorskite respectively). 26725456 2 54 theme dietary 538:544 arg1 groups 556:561 two dietary treatment groups 534:561 two dietary treatment groups; control and palygorskite 534:587 METHODS AND RESULTS Four hundred and thirty-two female, 1-day-old Hyline Brown chickens were equally and randomly allocated to two dietary treatment groups; control and palygorskite (0 and 0·5% palygorskite respectively). 26725456 2 54 theme dietary 538:544 arg1 palygorskite 576:587 palygorskite 576:587 palygorskite 576:587 METHODS AND RESULTS Four hundred and thirty-two female, 1-day-old Hyline Brown chickens were equally and randomly allocated to two dietary treatment groups; control and palygorskite (0 and 0·5% palygorskite respectively). 26725456 5 55 theme laying 830:835 arg1 cages 837:841 laying cages 830:841 laying cages 830:841 At the end of the rearing period, 53 birds per group were transferred to laying cages without any changes in their respective dietary treatments. 26725456 0 56 from microbiota 113:122 arg1 pullets 134:140 laying pullets 127:140 laying pullets 127:140 Dietary supplementation with the clay mineral palygorskite affects performance and beneficially modulates caecal microbiota in laying pullets. 26725456 8 57 theme period 1230:1235 arg1 end 1211:1213 the end 1207:1213 the end of the rearing period 1207:1235 CONCLUSIONS Palygorskite dietary supplementation increased the uniformity of the relative group at the end of the rearing period. 26725456 1 58 theme microbial 384:392 arg1 communities 394:404 caecal microbial communities 377:404 caecal microbial communities 377:404 AIMS The objective of this study was twofold: (i) to examine the effect of early-posthatch dietary inclusion of the clay mineral palygorskite on laying pullets' growth and (ii) to determine the potential effects of the latter diet on caecal microbial communities. 26725456 8 59 from end 1211:1213 arg1 uniformity 1171:1180 the uniformity 1167:1180 the uniformity of the relative group at the end of the rearing period 1167:1235 CONCLUSIONS Palygorskite dietary supplementation increased the uniformity of the relative group at the end of the rearing period. 26725456 1 60 dep examine 196:202 arg1 i 190:190 i 190:190 i 190:190 AIMS The objective of this study was twofold: (i) to examine the effect of early-posthatch dietary inclusion of the clay mineral palygorskite on laying pullets' growth and (ii) to determine the potential effects of the latter diet on caecal microbial communities. 26725456 11 61 theme beneficial 1664:1673 arg1 effect 1675:1680 the beneficial effect 1660:1680 the beneficial effect of palygorskite (a clay mineral) to pullets growth and health 1660:1742 SIGNIFICANCE AND IMPACT OF THE STUDY The novelty of this study lies to the beneficial effect of palygorskite (a clay mineral) to pullets growth and health, likely through modulation of the gut microbiota. 26725456 11 62 dep pullets 1718:1724 arg1 pullets 1718:1724 pullets growth and health 1718:1742 pullets growth and health 1718:1742 SIGNIFICANCE AND IMPACT OF THE STUDY The novelty of this study lies to the beneficial effect of palygorskite (a clay mineral) to pullets growth and health, likely through modulation of the gut microbiota. 26725456 11 62 dep pullets 1718:1724 arg1 health 1737:1742 health 1737:1742 health 1737:1742 SIGNIFICANCE AND IMPACT OF THE STUDY The novelty of this study lies to the beneficial effect of palygorskite (a clay mineral) to pullets growth and health, likely through modulation of the gut microbiota. 26725456 11 62 dep pullets 1718:1724 arg1 growth 1726:1731 growth 1726:1731 growth 1726:1731 SIGNIFICANCE AND IMPACT OF THE STUDY The novelty of this study lies to the beneficial effect of palygorskite (a clay mineral) to pullets growth and health, likely through modulation of the gut microbiota. 26725456 10 63 from evident 1455:1461 arg1 caeca 1394:1398 the caeca 1390:1398 the caeca of the former pullets 1390:1420 Moreover, in the caeca of the former pullets a more favourable microbiota was evident; it comprised largely of bacteria that are major degraders of resistant polysaccharides and efficient in butyrate production. 26725456 4 64 theme conversion 692:701 arg1 ratio 703:707 feed conversion ratio 687:707 feed conversion ratio 687:707 Feed intake, feed conversion ratio, body weight gain and uniformity were assessed. 26725456 1 65 from effects 347:353 arg1 communities 394:404 caecal microbial communities 377:404 caecal microbial communities 377:404 AIMS The objective of this study was twofold: (i) to examine the effect of early-posthatch dietary inclusion of the clay mineral palygorskite on laying pullets' growth and (ii) to determine the potential effects of the latter diet on caecal microbial communities. 26725456 5 66 theme dietary 883:889 arg1 treatments 891:900 their respective dietary treatments 866:900 their respective dietary treatments 866:900 At the end of the rearing period, 53 birds per group were transferred to laying cages without any changes in their respective dietary treatments. 26725456 2 67 theme Hyline 473:478 arg1 chickens 486:493 1-day-old Hyline Brown chickens 463:493 1-day-old Hyline Brown chickens 463:493 METHODS AND RESULTS Four hundred and thirty-two female, 1-day-old Hyline Brown chickens were equally and randomly allocated to two dietary treatment groups; control and palygorskite (0 and 0·5% palygorskite respectively). 26725456 2 67 theme Hyline 473:478 arg1 female 455:460 female 455:460 female 455:460 METHODS AND RESULTS Four hundred and thirty-two female, 1-day-old Hyline Brown chickens were equally and randomly allocated to two dietary treatment groups; control and palygorskite (0 and 0·5% palygorskite respectively). 26725456 0 68 theme laying 127:132 arg1 pullets 134:140 laying pullets 127:140 laying pullets 127:140 Dietary supplementation with the clay mineral palygorskite affects performance and beneficially modulates caecal microbiota in laying pullets. 26725456 7 69 theme microbial 1085:1093 arg1 composition 1095:1105 caecal microbial composition 1078:1105 caecal microbial composition 1078:1105 Culture-independent and sequencing-based methods were used to analyse caecal microbial composition. 26725456 1 70 theme potential 337:345 arg1 effects 347:353 the potential effects 333:353 the potential effects of the latter diet on caecal microbial communities 333:404 AIMS The objective of this study was twofold: (i) to examine the effect of early-posthatch dietary inclusion of the clay mineral palygorskite on laying pullets' growth and (ii) to determine the potential effects of the latter diet on caecal microbial communities. 26725456 4 71 theme Feed 674:677 arg1 intake 679:684 Feed intake 674:684 Feed intake 674:684 Feed intake, feed conversion ratio, body weight gain and uniformity were assessed. 26725456 10 72 theme butyrate 1568:1575 arg1 production 1577:1586 butyrate production 1568:1586 butyrate production 1568:1586 Moreover, in the caeca of the former pullets a more favourable microbiota was evident; it comprised largely of bacteria that are major degraders of resistant polysaccharides and efficient in butyrate production. 26725456 1 73 theme mineral 264:270 arg1 palygorskite 272:283 the clay mineral palygorskite 255:283 the clay mineral palygorskite 255:283 AIMS The objective of this study was twofold: (i) to examine the effect of early-posthatch dietary inclusion of the clay mineral palygorskite on laying pullets' growth and (ii) to determine the potential effects of the latter diet on caecal microbial communities. 26725456 0 74 theme mineral 38:44 arg1 palygorskite 46:57 the clay mineral palygorskite 29:57 the clay mineral palygorskite 29:57 Dietary supplementation with the clay mineral palygorskite affects performance and beneficially modulates caecal microbiota in laying pullets. 26725456 11 75 dep SIGNIFICANCE 1589:1600 arg1 novelty 1630:1636 The novelty 1626:1636 SIGNIFICANCE AND IMPACT OF THE STUDY The novelty of this study 1589:1650 SIGNIFICANCE AND IMPACT OF THE STUDY The novelty of this study lies to the beneficial effect of palygorskite (a clay mineral) to pullets growth and health, likely through modulation of the gut microbiota. 26725456 10 76 theme former 1407:1412 arg1 pullets 1414:1420 the former pullets 1403:1420 the former pullets 1403:1420 Moreover, in the caeca of the former pullets a more favourable microbiota was evident; it comprised largely of bacteria that are major degraders of resistant polysaccharides and efficient in butyrate production. 26725456 11 77 theme STUDY 1620:1624 arg1 IMPACT 1606:1611 IMPACT 1606:1611 IMPACT 1606:1611 SIGNIFICANCE AND IMPACT OF THE STUDY The novelty of this study lies to the beneficial effect of palygorskite (a clay mineral) to pullets growth and health, likely through modulation of the gut microbiota. 26725456 11 77 theme STUDY 1620:1624 arg1 SIGNIFICANCE 1589:1600 SIGNIFICANCE 1589:1600 SIGNIFICANCE 1589:1600 SIGNIFICANCE AND IMPACT OF THE STUDY The novelty of this study lies to the beneficial effect of palygorskite (a clay mineral) to pullets growth and health, likely through modulation of the gut microbiota. 26725456 9 78 theme caecal 1308:1313 arg1 profiles 1325:1332 different and more homogeneous caecal microbial profiles 1277:1332 different and more homogeneous caecal microbial profiles 1277:1332 Pullets that received palygorskite had different and more homogeneous caecal microbial profiles at onset of lay when compared to controls. 26725456 0 79 with supplementation 8:22 arg1 palygorskite 46:57 the clay mineral palygorskite 29:57 the clay mineral palygorskite 29:57 Dietary supplementation with the clay mineral palygorskite affects performance and beneficially modulates caecal microbiota in laying pullets. 26725456 5 80 from changes 855:861 arg1 treatments 891:900 their respective dietary treatments 866:900 their respective dietary treatments 866:900 At the end of the rearing period, 53 birds per group were transferred to laying cages without any changes in their respective dietary treatments. 26725456 10 81 theme favourable 1429:1438 arg1 microbiota 1440:1449 a more favourable microbiota 1422:1449 a more favourable microbiota 1422:1449 Moreover, in the caeca of the former pullets a more favourable microbiota was evident; it comprised largely of bacteria that are major degraders of resistant polysaccharides and efficient in butyrate production. 26725456 10 81 theme favourable 1429:1438 arg1 evident 1455:1461 evident 1455:1461 evident 1455:1461 Moreover, in the caeca of the former pullets a more favourable microbiota was evident; it comprised largely of bacteria that are major degraders of resistant polysaccharides and efficient in butyrate production. 26725456 4 82 theme weight 715:720 arg1 gain 722:725 body weight gain 710:725 body weight gain 710:725 Feed intake, feed conversion ratio, body weight gain and uniformity were assessed. 26725456 3 83 theme floor 649:653 arg1 pens 655:658 floor pens 649:658 floor pens 649:658 They were reared in floor pens for 18 weeks. 26725456 1 84 theme early-posthatch 218:232 arg1 inclusion 242:250 early-posthatch dietary inclusion 218:250 early-posthatch dietary inclusion of the clay mineral palygorskite 218:283 AIMS The objective of this study was twofold: (i) to examine the effect of early-posthatch dietary inclusion of the clay mineral palygorskite on laying pullets' growth and (ii) to determine the potential effects of the latter diet on caecal microbial communities. 26725456 9 85 theme lay 1346:1348 arg1 onset 1337:1341 onset 1337:1341 onset of lay 1337:1348 Pullets that received palygorskite had different and more homogeneous caecal microbial profiles at onset of lay when compared to controls. 26695194 5 0 from effects 847:853 arg1 preservation 868:879 the preservation 864:879 the preservation of microbial cells 864:898 We also evaluated the effects of Si on the preservation of microbial cells during the whole process. 26695194 1 1 theme microbial 153:161 arg1 life 163:166 microbial life 153:166 microbial life since its emergence on early Earth 153:201 The reconstruction of the history of microbial life since its emergence on early Earth is impaired by the difficulty to prove the biogenicity of putative microfossils in the rock record. 26695194 0 2 theme microbial 68:76 arg1 cells 78:82 microbial cells 68:82 microbial cells 68:82 Limited influence of Si on the preservation of Fe mineral-encrusted microbial cells during experimental diagenesis. 26695194 0 3 from influence 8:16 arg1 preservation 31:42 the preservation 27:42 the preservation of Fe 27:48 Limited influence of Si on the preservation of Fe mineral-encrusted microbial cells during experimental diagenesis. 26695194 2 4 theme diagenesis 543:552 arg1 typical 532:538 typical 532:538 typical 532:538 While most of the oldest rocks on Earth have been exposed to different grades of diagenetic alterations, little is known about how the remains of micro-organisms evolve when exposed to pressure (P) and temperature (T) conditions typical of diagenesis. 26695194 1 5 theme life 163:166 arg1 history 142:148 the history 138:148 the history of microbial life since its emergence on early Earth 138:201 The reconstruction of the history of microbial life since its emergence on early Earth is impaired by the difficulty to prove the biogenicity of putative microfossils in the rock record. 26695194 0 6 theme experimental 91:102 arg1 diagenesis 104:113 experimental diagenesis 91:113 experimental diagenesis 91:113 Limited influence of Si on the preservation of Fe mineral-encrusted microbial cells during experimental diagenesis. 26695194 1 7 from life 163:166 arg1 Earth 197:201 early Earth 191:201 early Earth 191:201 The reconstruction of the history of microbial life since its emergence on early Earth is impaired by the difficulty to prove the biogenicity of putative microfossils in the rock record. 26695194 10 8 theme diagenetic 1683:1692 arg1 conditions 1694:1703 diagenetic conditions 1683:1703 diagenetic conditions 1683:1703 Other organic compounds, such as lipids and extracellular polysaccharides seemed well preserved after exposure to diagenetic conditions. 26695194 2 9 theme pressure 488:495 arg1 conditions 521:530 pressure (P) and temperature (T) conditions 488:530 pressure (P) and temperature (T) conditions typical of diagenesis 488:552 While most of the oldest rocks on Earth have been exposed to different grades of diagenetic alterations, little is known about how the remains of micro-organisms evolve when exposed to pressure (P) and temperature (T) conditions typical of diagenesis. 26695194 3 10 theme chemical 636:643 arg1 biosignatures 645:657 morphological, mineralogical, and chemical biosignatures 602:657 morphological, mineralogical, and chemical biosignatures exhibited by Fe mineral-encrusted cells of the bacterium Acidovorax sp 602:728 Using spectroscopy and microscopy, we compared morphological, mineralogical, and chemical biosignatures exhibited by Fe mineral-encrusted cells of the bacterium Acidovorax sp. 26695194 2 11 theme typical 532:538 arg1 conditions 521:530 pressure (P) and temperature (T) conditions 488:530 pressure (P) and temperature (T) conditions typical of diagenesis 488:552 While most of the oldest rocks on Earth have been exposed to different grades of diagenetic alterations, little is known about how the remains of micro-organisms evolve when exposed to pressure (P) and temperature (T) conditions typical of diagenesis. 26695194 1 12 from history 142:148 arg1 Earth 197:201 early Earth 191:201 early Earth 191:201 The reconstruction of the history of microbial life since its emergence on early Earth is impaired by the difficulty to prove the biogenicity of putative microfossils in the rock record. 26695194 9 13 theme several 1406:1412 arg1 months 1414:1419 several months 1406:1419 several months 1406:1419 Proteins-the most abundant cellular components-were preserved over several months at ambient conditions but disappeared after incubations at high temperature and pressure conditions, both in the presence and in the absence of Si. 26695194 2 14 dep the 434:436 arg1 remains 438:444 remains 438:444 remains 438:444 While most of the oldest rocks on Earth have been exposed to different grades of diagenetic alterations, little is known about how the remains of micro-organisms evolve when exposed to pressure (P) and temperature (T) conditions typical of diagenesis. 26695194 5 15 theme microbial 884:892 arg1 cells 894:898 microbial cells 884:898 microbial cells 884:898 We also evaluated the effects of Si on the preservation of microbial cells during the whole process. 26695194 7 16 theme Fe-encrusted 1049:1060 arg1 cells 1062:1066 Fe-encrusted cells 1049:1066 Fe-encrusted cells 1049:1066 Fe-encrusted cells were morphologically well preserved after 1 week at 250 °C-140 MPa and after 16 weeks at 170 °C-120 MPa in the presence or in the absence of Si. 26695194 4 17 theme long-term 744:752 arg1 incubation 754:763 long-term incubation 744:763 long-term incubation under ambient conditions and after experimental diagenesis 744:822 BoFeN1 after long-term incubation under ambient conditions and after experimental diagenesis. 26695194 9 18 theme ambient 1424:1430 arg1 conditions 1432:1441 ambient conditions 1424:1441 ambient conditions 1424:1441 Proteins-the most abundant cellular components-were preserved over several months at ambient conditions but disappeared after incubations at high temperature and pressure conditions, both in the presence and in the absence of Si. 26695194 2 19 theme different 364:372 arg1 grades 374:379 different grades 364:379 different grades of diagenetic alterations 364:405 While most of the oldest rocks on Earth have been exposed to different grades of diagenetic alterations, little is known about how the remains of micro-organisms evolve when exposed to pressure (P) and temperature (T) conditions typical of diagenesis. 26695194 11 20 theme potential 1761:1769 arg1 preservation 1771:1782 potential preservation 1761:1782 potential preservation 1761:1782 This study provides insights about the composition and potential preservation of microfossils that could have formed in Fe- and Si-rich Precambrian oceans. 26695194 3 21 theme Fe 672:673 arg1 cells 693:697 Fe mineral-encrusted cells 672:697 Fe mineral-encrusted cells of the bacterium Acidovorax sp 672:728 Using spectroscopy and microscopy, we compared morphological, mineralogical, and chemical biosignatures exhibited by Fe mineral-encrusted cells of the bacterium Acidovorax sp. 26695194 9 22 theme pressure 1501:1508 arg1 conditions 1510:1519 pressure conditions 1501:1519 pressure conditions 1501:1519 Proteins-the most abundant cellular components-were preserved over several months at ambient conditions but disappeared after incubations at high temperature and pressure conditions, both in the presence and in the absence of Si. 26695194 8 23 theme Si 1307:1308 arg1 presence 1295:1302 the presence 1291:1302 the presence of Si more goethite 1291:1322 Some goethite transformed to hematite and magnetite at 250 °C-140 MPa, but in the presence of Si more goethite was preserved. 26695194 10 24 theme extracellular 1613:1625 arg1 polysaccharides 1627:1641 extracellular polysaccharides 1613:1641 extracellular polysaccharides 1613:1641 Other organic compounds, such as lipids and extracellular polysaccharides seemed well preserved after exposure to diagenetic conditions. 26695194 10 25 theme organic 1575:1581 arg1 lipids 1602:1607 lipids 1602:1607 lipids 1602:1607 Other organic compounds, such as lipids and extracellular polysaccharides seemed well preserved after exposure to diagenetic conditions. 26695194 10 25 theme organic 1575:1581 arg1 polysaccharides 1627:1641 extracellular polysaccharides 1613:1641 extracellular polysaccharides 1613:1641 Other organic compounds, such as lipids and extracellular polysaccharides seemed well preserved after exposure to diagenetic conditions. 26695194 10 25 theme organic 1575:1581 arg1 compounds 1583:1591 Other organic compounds 1569:1591 Other organic compounds 1569:1591 Other organic compounds, such as lipids and extracellular polysaccharides seemed well preserved after exposure to diagenetic conditions. 26695194 3 26 theme mineral-encrusted 675:691 arg1 cells 693:697 Fe mineral-encrusted cells 672:697 Fe mineral-encrusted cells of the bacterium Acidovorax sp 672:728 Using spectroscopy and microscopy, we compared morphological, mineralogical, and chemical biosignatures exhibited by Fe mineral-encrusted cells of the bacterium Acidovorax sp. 26695194 10 27 theme Other 1569:1573 arg1 lipids 1602:1607 lipids 1602:1607 lipids 1602:1607 Other organic compounds, such as lipids and extracellular polysaccharides seemed well preserved after exposure to diagenetic conditions. 26695194 10 27 theme Other 1569:1573 arg1 polysaccharides 1627:1641 extracellular polysaccharides 1613:1641 extracellular polysaccharides 1613:1641 Other organic compounds, such as lipids and extracellular polysaccharides seemed well preserved after exposure to diagenetic conditions. 26695194 10 27 theme Other 1569:1573 arg1 compounds 1583:1591 Other organic compounds 1569:1591 Other organic compounds 1569:1591 Other organic compounds, such as lipids and extracellular polysaccharides seemed well preserved after exposure to diagenetic conditions. 26695194 2 28 from rocks 328:332 arg1 Earth 337:341 Earth 337:341 Earth 337:341 While most of the oldest rocks on Earth have been exposed to different grades of diagenetic alterations, little is known about how the remains of micro-organisms evolve when exposed to pressure (P) and temperature (T) conditions typical of diagenesis. 26695194 5 29 theme whole 911:915 arg1 process 917:923 the whole process 907:923 the whole process 907:923 We also evaluated the effects of Si on the preservation of microbial cells during the whole process. 26695194 9 30 theme high 1480:1483 arg1 temperature 1485:1495 high temperature 1480:1495 high temperature 1480:1495 Proteins-the most abundant cellular components-were preserved over several months at ambient conditions but disappeared after incubations at high temperature and pressure conditions, both in the presence and in the absence of Si. 26695194 0 31 theme Limited 0:6 arg1 influence 8:16 Limited influence 0:16 Limited influence of Si on the preservation of Fe 0:48 Limited influence of Si on the preservation of Fe mineral-encrusted microbial cells during experimental diagenesis. 26695194 1 32 theme putative 261:268 arg1 microfossils 270:281 putative microfossils 261:281 putative microfossils 261:281 The reconstruction of the history of microbial life since its emergence on early Earth is impaired by the difficulty to prove the biogenicity of putative microfossils in the rock record. 26695194 3 33 theme Acidovorax 716:725 arg1 sp 727:728 the bacterium Acidovorax sp 702:728 the bacterium Acidovorax sp 702:728 Using spectroscopy and microscopy, we compared morphological, mineralogical, and chemical biosignatures exhibited by Fe mineral-encrusted cells of the bacterium Acidovorax sp. 26695194 8 34 theme goethite 1315:1322 arg1 Si 1307:1308 Si 1307:1308 Si more goethite 1307:1322 Some goethite transformed to hematite and magnetite at 250 °C-140 MPa, but in the presence of Si more goethite was preserved. 26695194 5 35 theme Si 858:859 arg1 effects 847:853 the effects 843:853 the effects of Si on the preservation of microbial cells 843:898 We also evaluated the effects of Si on the preservation of microbial cells during the whole process. 26695194 0 36 theme Si 21:22 arg1 influence 8:16 Limited influence 0:16 Limited influence of Si on the preservation of Fe 0:48 Limited influence of Si on the preservation of Fe mineral-encrusted microbial cells during experimental diagenesis. 26695194 1 37 theme microfossils 270:281 arg1 biogenicity 246:256 the biogenicity 242:256 the biogenicity of putative microfossils 242:281 The reconstruction of the history of microbial life since its emergence on early Earth is impaired by the difficulty to prove the biogenicity of putative microfossils in the rock record. 26695194 2 38 theme temperature 505:515 arg1 conditions 521:530 pressure (P) and temperature (T) conditions 488:530 pressure (P) and temperature (T) conditions typical of diagenesis 488:552 While most of the oldest rocks on Earth have been exposed to different grades of diagenetic alterations, little is known about how the remains of micro-organisms evolve when exposed to pressure (P) and temperature (T) conditions typical of diagenesis. 26695194 9 39 theme Si 1565:1566 arg1 absence 1554:1560 the absence 1550:1560 the absence of Si 1550:1566 Proteins-the most abundant cellular components-were preserved over several months at ambient conditions but disappeared after incubations at high temperature and pressure conditions, both in the presence and in the absence of Si. 26695194 2 40 theme alterations 395:405 arg1 grades 374:379 different grades 364:379 different grades of diagenetic alterations 364:405 While most of the oldest rocks on Earth have been exposed to different grades of diagenetic alterations, little is known about how the remains of micro-organisms evolve when exposed to pressure (P) and temperature (T) conditions typical of diagenesis. 26695194 11 41 theme microfossils 1787:1798 arg1 composition 1745:1755 composition 1745:1755 composition 1745:1755 This study provides insights about the composition and potential preservation of microfossils that could have formed in Fe- and Si-rich Precambrian oceans. 26695194 11 41 theme microfossils 1787:1798 arg1 preservation 1771:1782 potential preservation 1761:1782 potential preservation 1761:1782 This study provides insights about the composition and potential preservation of microfossils that could have formed in Fe- and Si-rich Precambrian oceans. 26695194 7 42 from 170 °C-120 MPa 1157:1170 arg1 presence 1179:1186 the presence 1175:1186 the presence 1175:1186 Fe-encrusted cells were morphologically well preserved after 1 week at 250 °C-140 MPa and after 16 weeks at 170 °C-120 MPa in the presence or in the absence of Si. 26695194 7 42 from 170 °C-120 MPa 1157:1170 arg1 250 °C-140 MPa 1120:1133 250 °C-140 MPa 1120:1133 250 °C-140 MPa 1120:1133 Fe-encrusted cells were morphologically well preserved after 1 week at 250 °C-140 MPa and after 16 weeks at 170 °C-120 MPa in the presence or in the absence of Si. 26695194 7 43 theme Si 1209:1210 arg1 absence 1198:1204 the absence 1194:1204 the absence of Si 1194:1210 Fe-encrusted cells were morphologically well preserved after 1 week at 250 °C-140 MPa and after 16 weeks at 170 °C-120 MPa in the presence or in the absence of Si. 26695194 2 44 theme diagenetic 384:393 arg1 alterations 395:405 diagenetic alterations 384:405 diagenetic alterations 384:405 While most of the oldest rocks on Earth have been exposed to different grades of diagenetic alterations, little is known about how the remains of micro-organisms evolve when exposed to pressure (P) and temperature (T) conditions typical of diagenesis. 26695194 3 45 theme bacterium 706:714 arg1 sp 727:728 the bacterium Acidovorax sp 702:728 the bacterium Acidovorax sp 702:728 Using spectroscopy and microscopy, we compared morphological, mineralogical, and chemical biosignatures exhibited by Fe mineral-encrusted cells of the bacterium Acidovorax sp. 26695194 3 46 theme morphological 602:614 arg1 biosignatures 645:657 morphological, mineralogical, and chemical biosignatures 602:657 morphological, mineralogical, and chemical biosignatures exhibited by Fe mineral-encrusted cells of the bacterium Acidovorax sp 602:728 Using spectroscopy and microscopy, we compared morphological, mineralogical, and chemical biosignatures exhibited by Fe mineral-encrusted cells of the bacterium Acidovorax sp. 26695194 6 47 theme ambient 929:935 arg1 conditions 937:946 ambient conditions 929:946 ambient conditions 929:946 At ambient conditions, Si affected the morphology but not the identity (goethite) of Fe minerals that formed around cells. 26695194 6 48 theme minerals 1014:1021 arg1 goethite 998:1005 goethite 998:1005 goethite 998:1005 At ambient conditions, Si affected the morphology but not the identity (goethite) of Fe minerals that formed around cells. 26695194 6 48 theme minerals 1014:1021 arg1 identity 988:995 the identity 984:995 the morphology but not the identity (goethite) of Fe minerals that formed around cells 961:1046 At ambient conditions, Si affected the morphology but not the identity (goethite) of Fe minerals that formed around cells. 26695194 1 49 theme rock 290:293 arg1 record 295:300 the rock record 286:300 the rock record 286:300 The reconstruction of the history of microbial life since its emergence on early Earth is impaired by the difficulty to prove the biogenicity of putative microfossils in the rock record. 26695194 3 50 theme sp 727:728 arg1 cells 693:697 Fe mineral-encrusted cells 672:697 Fe mineral-encrusted cells of the bacterium Acidovorax sp 672:728 Using spectroscopy and microscopy, we compared morphological, mineralogical, and chemical biosignatures exhibited by Fe mineral-encrusted cells of the bacterium Acidovorax sp. 26695194 11 51 dep composition 1745:1755 arg1 the 1741:1743 the 1741:1743 the 1741:1743 This study provides insights about the composition and potential preservation of microfossils that could have formed in Fe- and Si-rich Precambrian oceans. 26695194 9 52 from incubations 1465:1475 arg1 presence 1534:1541 the presence 1530:1541 the presence 1530:1541 Proteins-the most abundant cellular components-were preserved over several months at ambient conditions but disappeared after incubations at high temperature and pressure conditions, both in the presence and in the absence of Si. 26695194 9 52 from incubations 1465:1475 arg1 absence 1554:1560 the absence 1550:1560 the absence of Si 1550:1566 Proteins-the most abundant cellular components-were preserved over several months at ambient conditions but disappeared after incubations at high temperature and pressure conditions, both in the presence and in the absence of Si. 26695194 2 53 theme oldest 321:326 arg1 rocks 328:332 the oldest rocks 317:332 the oldest rocks on Earth 317:341 While most of the oldest rocks on Earth have been exposed to different grades of diagenetic alterations, little is known about how the remains of micro-organisms evolve when exposed to pressure (P) and temperature (T) conditions typical of diagenesis. 26695194 4 54 theme experimental 800:811 arg1 diagenesis 813:822 experimental diagenesis 800:822 experimental diagenesis 800:822 BoFeN1 after long-term incubation under ambient conditions and after experimental diagenesis. 26695194 5 55 theme cells 894:898 arg1 preservation 868:879 the preservation 864:879 the preservation of microbial cells 864:898 We also evaluated the effects of Si on the preservation of microbial cells during the whole process. 26695194 9 56 from temperature 1485:1495 arg1 incubations 1465:1475 incubations 1465:1475 incubations at high temperature and pressure conditions, both in the presence and in the absence of Si 1465:1566 Proteins-the most abundant cellular components-were preserved over several months at ambient conditions but disappeared after incubations at high temperature and pressure conditions, both in the presence and in the absence of Si. 26695194 1 57 from Earth 197:201 arg1 history 142:148 the history 138:148 the history of microbial life since its emergence on early Earth 138:201 The reconstruction of the history of microbial life since its emergence on early Earth is impaired by the difficulty to prove the biogenicity of putative microfossils in the rock record. 26695194 9 58 theme Proteins-the 1339:1350 arg1 components-were 1375:1389 Proteins-the most abundant cellular components-were 1339:1389 Proteins-the most abundant cellular components-were 1339:1389 Proteins-the most abundant cellular components-were preserved over several months at ambient conditions but disappeared after incubations at high temperature and pressure conditions, both in the presence and in the absence of Si. 26695194 6 59 theme Fe 1011:1012 arg1 minerals 1014:1021 Fe minerals 1011:1021 Fe minerals that formed around cells 1011:1046 At ambient conditions, Si affected the morphology but not the identity (goethite) of Fe minerals that formed around cells. 26695194 3 60 theme mineralogical 617:629 arg1 biosignatures 645:657 morphological, mineralogical, and chemical biosignatures 602:657 morphological, mineralogical, and chemical biosignatures exhibited by Fe mineral-encrusted cells of the bacterium Acidovorax sp 602:728 Using spectroscopy and microscopy, we compared morphological, mineralogical, and chemical biosignatures exhibited by Fe mineral-encrusted cells of the bacterium Acidovorax sp. 26695194 1 61 theme early 191:195 arg1 Earth 197:201 early Earth 191:201 early Earth 191:201 The reconstruction of the history of microbial life since its emergence on early Earth is impaired by the difficulty to prove the biogenicity of putative microfossils in the rock record. 26695194 1 62 theme history 142:148 arg1 reconstruction 120:133 The reconstruction 116:133 The reconstruction of the history of microbial life since its emergence on early Earth 116:201 The reconstruction of the history of microbial life since its emergence on early Earth is impaired by the difficulty to prove the biogenicity of putative microfossils in the rock record. 26695194 9 63 theme abundant 1357:1364 arg1 components-were 1375:1389 Proteins-the most abundant cellular components-were 1339:1389 Proteins-the most abundant cellular components-were 1339:1389 Proteins-the most abundant cellular components-were preserved over several months at ambient conditions but disappeared after incubations at high temperature and pressure conditions, both in the presence and in the absence of Si. 26695194 0 64 theme Fe 47:48 arg1 preservation 31:42 the preservation 27:42 the preservation of Fe 27:48 Limited influence of Si on the preservation of Fe mineral-encrusted microbial cells during experimental diagenesis. 26695194 4 65 theme ambient 771:777 arg1 conditions 779:788 ambient conditions 771:788 ambient conditions 771:788 BoFeN1 after long-term incubation under ambient conditions and after experimental diagenesis. 26695194 9 66 theme cellular 1366:1373 arg1 components-were 1375:1389 Proteins-the most abundant cellular components-were 1339:1389 Proteins-the most abundant cellular components-were 1339:1389 Proteins-the most abundant cellular components-were preserved over several months at ambient conditions but disappeared after incubations at high temperature and pressure conditions, both in the presence and in the absence of Si. 26563650 0 0 theme hepatoma 92:99 arg1 cells 111:115 human hepatoma SMMC-7721 cells 86:115 human hepatoma SMMC-7721 cells 86:115 Composition of Lycium barbarum polysaccharides and their apoptosis-inducing effect on human hepatoma SMMC-7721 cells. 26563650 6 1 theme % 996:996 arg1 ratio 972:976 an inhibition ratio 958:976 an inhibition ratio of 26.70 and 45.13%, respectively 958:1010 LBP-d and LBP-e blocked SMMC-7721 cells at the G0/G1 and S phases with an inhibition ratio of 26.70 and 45.13%, respectively, and enhanced the concentration of Ca(2+) in the cytoplasm of SMMC-7721. 26563650 0 2 theme human 86:90 arg1 cells 111:115 human hepatoma SMMC-7721 cells 86:115 human hepatoma SMMC-7721 cells 86:115 Composition of Lycium barbarum polysaccharides and their apoptosis-inducing effect on human hepatoma SMMC-7721 cells. 26563650 3 3 from sugars 494:499 arg1 proportions 514:524 different proportions 504:524 different proportions 504:524 RESULTS The results showed that LBP-d and LBP-e both consist of protein, uronic acid, and neutral sugars in different proportions. 26563650 4 4 theme gas 569:571 arg1 chromatography 573:586 gas chromatography 569:586 gas chromatography 569:586 The structure of LBP was characterized by gas chromatography, periodate oxidation, and Smith degradation. 26563650 0 5 from Composition 0:10 arg1 cells 111:115 human hepatoma SMMC-7721 cells 86:115 human hepatoma SMMC-7721 cells 86:115 Composition of Lycium barbarum polysaccharides and their apoptosis-inducing effect on human hepatoma SMMC-7721 cells. 26563650 3 6 dep RESULTS 396:402 arg1 showed 416:421 showed 416:421 showed that LBP-d and LBP-e both consist of protein, uronic acid, and neutral sugars in different proportions 416:524 RESULTS The results showed that LBP-d and LBP-e both consist of protein, uronic acid, and neutral sugars in different proportions. 26563650 2 7 theme hepatoma 313:320 arg1 cells 332:336 human hepatoma SMMC-7721 cells 307:336 human hepatoma SMMC-7721 cells 307:336 The molecular structures and apoptosis-inducing activities on human hepatoma SMMC-7721 cells of two LBP fractions, LBP-d and LBP-e, were investigated. 26563650 2 8 theme SMMC-7721 322:330 arg1 cells 332:336 human hepatoma SMMC-7721 cells 307:336 human hepatoma SMMC-7721 cells 307:336 The molecular structures and apoptosis-inducing activities on human hepatoma SMMC-7721 cells of two LBP fractions, LBP-d and LBP-e, were investigated. 26563650 4 9 theme periodate 589:597 arg1 oxidation 599:607 periodate oxidation 589:607 periodate oxidation 589:607 The structure of LBP was characterized by gas chromatography, periodate oxidation, and Smith degradation. 26563650 0 10 theme SMMC-7721 101:109 arg1 cells 111:115 human hepatoma SMMC-7721 cells 86:115 human hepatoma SMMC-7721 cells 86:115 Composition of Lycium barbarum polysaccharides and their apoptosis-inducing effect on human hepatoma SMMC-7721 cells. 26563650 2 11 theme human 307:311 arg1 cells 332:336 human hepatoma SMMC-7721 cells 307:336 human hepatoma SMMC-7721 cells 307:336 The molecular structures and apoptosis-inducing activities on human hepatoma SMMC-7721 cells of two LBP fractions, LBP-d and LBP-e, were investigated. 26563650 7 12 theme galactose 1138:1146 arg1 higher 1167:1172 higher 1167:1172 higher 1167:1172 CONCLUSION The contents of protein, uronic acid, and galactose in LBP-e were much higher than those in LBP-d, which might responsible for their different bioactivities. 26563650 7 12 theme galactose 1138:1146 arg1 contents 1100:1107 The contents 1096:1107 The contents of protein, uronic acid, and galactose in LBP-e 1096:1155 CONCLUSION The contents of protein, uronic acid, and galactose in LBP-e were much higher than those in LBP-d, which might responsible for their different bioactivities. 26563650 1 13 theme natural 171:177 arg1 component 190:198 a natural functional component 169:198 a natural functional component that has a variety of biological activities 169:242 BACKGROUND Lycium barbarum polysaccharide (LBP) is a natural functional component that has a variety of biological activities. 26563650 1 13 theme natural 171:177 arg1 polysaccharide 145:158 BACKGROUND Lycium barbarum polysaccharide 118:158 BACKGROUND Lycium barbarum polysaccharide (LBP) 118:164 BACKGROUND Lycium barbarum polysaccharide (LBP) is a natural functional component that has a variety of biological activities. 26563650 2 14 dep structures 259:268 arg1 The 245:247 The 245:247 The 245:247 The molecular structures and apoptosis-inducing activities on human hepatoma SMMC-7721 cells of two LBP fractions, LBP-d and LBP-e, were investigated. 26563650 3 15 from acid 476:479 arg1 proportions 514:524 different proportions 504:524 different proportions 504:524 RESULTS The results showed that LBP-d and LBP-e both consist of protein, uronic acid, and neutral sugars in different proportions. 26563650 8 16 theme chemotherapeutic 1313:1328 arg1 LBP 1278:1280 LBP 1278:1280 LBP 1278:1280 The results showed that LBP can be provided as a potential chemotherapeutic agent drug to treat cancer. 26563650 8 16 theme chemotherapeutic 1313:1328 arg1 drug 1336:1339 a potential chemotherapeutic agent drug 1301:1339 a potential chemotherapeutic agent drug to treat cancer 1301:1355 The results showed that LBP can be provided as a potential chemotherapeutic agent drug to treat cancer. 26563650 1 17 theme functional 179:188 arg1 component 190:198 a natural functional component 169:198 a natural functional component that has a variety of biological activities 169:242 BACKGROUND Lycium barbarum polysaccharide (LBP) is a natural functional component that has a variety of biological activities. 26563650 1 17 theme functional 179:188 arg1 polysaccharide 145:158 BACKGROUND Lycium barbarum polysaccharide 118:158 BACKGROUND Lycium barbarum polysaccharide (LBP) 118:164 BACKGROUND Lycium barbarum polysaccharide (LBP) is a natural functional component that has a variety of biological activities. 26563650 3 18 dep LBP-d 428:432 arg1 both 444:447 both 444:447 both 444:447 RESULTS The results showed that LBP-d and LBP-e both consist of protein, uronic acid, and neutral sugars in different proportions. 26563650 6 19 theme Ca 1047:1048 arg1 concentration 1030:1042 the concentration 1026:1042 the concentration of Ca(2+) 1026:1052 LBP-d and LBP-e blocked SMMC-7721 cells at the G0/G1 and S phases with an inhibition ratio of 26.70 and 45.13%, respectively, and enhanced the concentration of Ca(2+) in the cytoplasm of SMMC-7721. 26563650 2 20 from structures 259:268 arg1 cells 332:336 human hepatoma SMMC-7721 cells 307:336 human hepatoma SMMC-7721 cells 307:336 The molecular structures and apoptosis-inducing activities on human hepatoma SMMC-7721 cells of two LBP fractions, LBP-d and LBP-e, were investigated. 26563650 0 21 theme barbarum 22:29 arg1 polysaccharides 31:45 Lycium barbarum polysaccharides 15:45 Lycium barbarum polysaccharides 15:45 Composition of Lycium barbarum polysaccharides and their apoptosis-inducing effect on human hepatoma SMMC-7721 cells. 26563650 4 22 theme LBP 544:546 arg1 structure 531:539 The structure 527:539 The structure of LBP 527:546 The structure of LBP was characterized by gas chromatography, periodate oxidation, and Smith degradation. 26563650 7 23 dep CONCLUSION 1085:1094 arg1 higher 1167:1172 higher 1167:1172 higher 1167:1172 CONCLUSION The contents of protein, uronic acid, and galactose in LBP-e were much higher than those in LBP-d, which might responsible for their different bioactivities. 26563650 7 23 dep CONCLUSION 1085:1094 arg1 contents 1100:1107 The contents 1096:1107 The contents of protein, uronic acid, and galactose in LBP-e 1096:1155 CONCLUSION The contents of protein, uronic acid, and galactose in LBP-e were much higher than those in LBP-d, which might responsible for their different bioactivities. 26563650 6 24 theme inhibition 961:970 arg1 ratio 972:976 an inhibition ratio 958:976 an inhibition ratio of 26.70 and 45.13%, respectively 958:1010 LBP-d and LBP-e blocked SMMC-7721 cells at the G0/G1 and S phases with an inhibition ratio of 26.70 and 45.13%, respectively, and enhanced the concentration of Ca(2+) in the cytoplasm of SMMC-7721. 26563650 0 25 theme Lycium 15:20 arg1 polysaccharides 31:45 Lycium barbarum polysaccharides 15:45 Lycium barbarum polysaccharides 15:45 Composition of Lycium barbarum polysaccharides and their apoptosis-inducing effect on human hepatoma SMMC-7721 cells. 26563650 1 26 theme BACKGROUND 118:127 arg1 polysaccharide 145:158 BACKGROUND Lycium barbarum polysaccharide 118:158 BACKGROUND Lycium barbarum polysaccharide (LBP) 118:164 BACKGROUND Lycium barbarum polysaccharide (LBP) is a natural functional component that has a variety of biological activities. 26563650 1 26 theme BACKGROUND 118:127 arg1 component 190:198 a natural functional component 169:198 a natural functional component that has a variety of biological activities 169:242 BACKGROUND Lycium barbarum polysaccharide (LBP) is a natural functional component that has a variety of biological activities. 26563650 1 26 theme BACKGROUND 118:127 arg1 LBP 161:163 LBP 161:163 LBP 161:163 BACKGROUND Lycium barbarum polysaccharide (LBP) is a natural functional component that has a variety of biological activities. 26563650 3 27 theme uronic 469:474 arg1 acid 476:479 uronic acid 469:479 uronic acid 469:479 RESULTS The results showed that LBP-d and LBP-e both consist of protein, uronic acid, and neutral sugars in different proportions. 26563650 3 28 theme neutral 486:492 arg1 sugars 494:499 neutral sugars 486:499 neutral sugars in different proportions 486:524 RESULTS The results showed that LBP-d and LBP-e both consist of protein, uronic acid, and neutral sugars in different proportions. 26563650 7 29 theme uronic 1121:1126 arg1 acid 1128:1131 uronic acid 1121:1131 uronic acid 1121:1131 CONCLUSION The contents of protein, uronic acid, and galactose in LBP-e were much higher than those in LBP-d, which might responsible for their different bioactivities. 26563650 7 30 theme different 1229:1237 arg1 bioactivities 1239:1251 their different bioactivities 1223:1251 their different bioactivities 1223:1251 CONCLUSION The contents of protein, uronic acid, and galactose in LBP-e were much higher than those in LBP-d, which might responsible for their different bioactivities. 26563650 0 31 theme polysaccharides 31:45 arg1 Composition 0:10 Composition 0:10 Composition of Lycium barbarum polysaccharides 0:45 Composition of Lycium barbarum polysaccharides and their apoptosis-inducing effect on human hepatoma SMMC-7721 cells. 26563650 0 31 theme polysaccharides 31:45 arg1 effect 76:81 their apoptosis-inducing effect 51:81 their apoptosis-inducing effect on human hepatoma SMMC-7721 cells 51:115 Composition of Lycium barbarum polysaccharides and their apoptosis-inducing effect on human hepatoma SMMC-7721 cells. 26563650 8 32 theme potential 1303:1311 arg1 LBP 1278:1280 LBP 1278:1280 LBP 1278:1280 The results showed that LBP can be provided as a potential chemotherapeutic agent drug to treat cancer. 26563650 8 32 theme potential 1303:1311 arg1 drug 1336:1339 a potential chemotherapeutic agent drug 1301:1339 a potential chemotherapeutic agent drug to treat cancer 1301:1355 The results showed that LBP can be provided as a potential chemotherapeutic agent drug to treat cancer. 26563650 6 33 theme G0/G1 934:938 arg1 phases 946:951 the G0/G1 and S phases 930:951 phases 946:951 LBP-d and LBP-e blocked SMMC-7721 cells at the G0/G1 and S phases with an inhibition ratio of 26.70 and 45.13%, respectively, and enhanced the concentration of Ca(2+) in the cytoplasm of SMMC-7721. 26563650 5 34 dep monosaccharides 670:684 arg1 glucose 756:762 glucose 756:762 glucose 756:762 LBP-d was composed of eight kinds of monosaccharides (fucose, ribose, rhamnose, arabinose, xylose, mannose, galactose, and glucose), while LBP-e was composed of six kinds of monosaccharides (fucose, rhamnose, arabinose, mannose, galactose, and glucose). 26563650 5 34 dep monosaccharides 670:684 arg1 ribose 695:700 ribose 695:700 ribose 695:700 LBP-d was composed of eight kinds of monosaccharides (fucose, ribose, rhamnose, arabinose, xylose, mannose, galactose, and glucose), while LBP-e was composed of six kinds of monosaccharides (fucose, rhamnose, arabinose, mannose, galactose, and glucose). 26563650 5 34 dep monosaccharides 670:684 arg1 rhamnose 703:710 rhamnose 703:710 rhamnose 703:710 LBP-d was composed of eight kinds of monosaccharides (fucose, ribose, rhamnose, arabinose, xylose, mannose, galactose, and glucose), while LBP-e was composed of six kinds of monosaccharides (fucose, rhamnose, arabinose, mannose, galactose, and glucose). 26563650 5 34 dep monosaccharides 670:684 arg1 mannose 732:738 mannose 732:738 mannose 732:738 LBP-d was composed of eight kinds of monosaccharides (fucose, ribose, rhamnose, arabinose, xylose, mannose, galactose, and glucose), while LBP-e was composed of six kinds of monosaccharides (fucose, rhamnose, arabinose, mannose, galactose, and glucose). 26563650 5 34 dep monosaccharides 670:684 arg1 monosaccharides 670:684 monosaccharides 670:684 monosaccharides (fucose, ribose, rhamnose, arabinose, xylose, mannose, galactose, and glucose) 670:763 LBP-d was composed of eight kinds of monosaccharides (fucose, ribose, rhamnose, arabinose, xylose, mannose, galactose, and glucose), while LBP-e was composed of six kinds of monosaccharides (fucose, rhamnose, arabinose, mannose, galactose, and glucose). 26563650 5 34 dep monosaccharides 670:684 arg1 galactose 741:749 galactose 741:749 galactose 741:749 LBP-d was composed of eight kinds of monosaccharides (fucose, ribose, rhamnose, arabinose, xylose, mannose, galactose, and glucose), while LBP-e was composed of six kinds of monosaccharides (fucose, rhamnose, arabinose, mannose, galactose, and glucose). 26563650 5 34 dep monosaccharides 670:684 arg1 fucose 687:692 fucose 687:692 fucose 687:692 LBP-d was composed of eight kinds of monosaccharides (fucose, ribose, rhamnose, arabinose, xylose, mannose, galactose, and glucose), while LBP-e was composed of six kinds of monosaccharides (fucose, rhamnose, arabinose, mannose, galactose, and glucose). 26563650 5 34 dep monosaccharides 670:684 arg1 arabinose 713:721 arabinose 713:721 arabinose 713:721 LBP-d was composed of eight kinds of monosaccharides (fucose, ribose, rhamnose, arabinose, xylose, mannose, galactose, and glucose), while LBP-e was composed of six kinds of monosaccharides (fucose, rhamnose, arabinose, mannose, galactose, and glucose). 26563650 5 34 dep monosaccharides 670:684 arg1 xylose 724:729 xylose 724:729 xylose 724:729 LBP-d was composed of eight kinds of monosaccharides (fucose, ribose, rhamnose, arabinose, xylose, mannose, galactose, and glucose), while LBP-e was composed of six kinds of monosaccharides (fucose, rhamnose, arabinose, mannose, galactose, and glucose). 26563650 0 35 theme apoptosis-inducing 57:74 arg1 effect 76:81 their apoptosis-inducing effect 51:81 their apoptosis-inducing effect on human hepatoma SMMC-7721 cells 51:115 Composition of Lycium barbarum polysaccharides and their apoptosis-inducing effect on human hepatoma SMMC-7721 cells. 26563650 0 36 from effect 76:81 arg1 cells 111:115 human hepatoma SMMC-7721 cells 86:115 human hepatoma SMMC-7721 cells 86:115 Composition of Lycium barbarum polysaccharides and their apoptosis-inducing effect on human hepatoma SMMC-7721 cells. 26563650 3 37 from protein 460:466 arg1 proportions 514:524 different proportions 504:524 different proportions 504:524 RESULTS The results showed that LBP-d and LBP-e both consist of protein, uronic acid, and neutral sugars in different proportions. 26563650 1 38 theme Lycium 129:134 arg1 polysaccharide 145:158 BACKGROUND Lycium barbarum polysaccharide 118:158 BACKGROUND Lycium barbarum polysaccharide (LBP) 118:164 BACKGROUND Lycium barbarum polysaccharide (LBP) is a natural functional component that has a variety of biological activities. 26563650 1 38 theme Lycium 129:134 arg1 component 190:198 a natural functional component 169:198 a natural functional component that has a variety of biological activities 169:242 BACKGROUND Lycium barbarum polysaccharide (LBP) is a natural functional component that has a variety of biological activities. 26563650 1 38 theme Lycium 129:134 arg1 LBP 161:163 LBP 161:163 LBP 161:163 BACKGROUND Lycium barbarum polysaccharide (LBP) is a natural functional component that has a variety of biological activities. 26563650 5 39 theme monosaccharides 670:684 arg1 kinds 661:665 eight kinds 655:665 eight kinds of monosaccharides (fucose, ribose, rhamnose, arabinose, xylose, mannose, galactose, and glucose) 655:763 LBP-d was composed of eight kinds of monosaccharides (fucose, ribose, rhamnose, arabinose, xylose, mannose, galactose, and glucose), while LBP-e was composed of six kinds of monosaccharides (fucose, rhamnose, arabinose, mannose, galactose, and glucose). 26563650 8 40 theme agent 1330:1334 arg1 LBP 1278:1280 LBP 1278:1280 LBP 1278:1280 The results showed that LBP can be provided as a potential chemotherapeutic agent drug to treat cancer. 26563650 8 40 theme agent 1330:1334 arg1 drug 1336:1339 a potential chemotherapeutic agent drug 1301:1339 a potential chemotherapeutic agent drug to treat cancer 1301:1355 The results showed that LBP can be provided as a potential chemotherapeutic agent drug to treat cancer. 26563650 5 41 dep monosaccharides 807:821 arg1 mannose 853:859 mannose 853:859 mannose 853:859 LBP-d was composed of eight kinds of monosaccharides (fucose, ribose, rhamnose, arabinose, xylose, mannose, galactose, and glucose), while LBP-e was composed of six kinds of monosaccharides (fucose, rhamnose, arabinose, mannose, galactose, and glucose). 26563650 5 41 dep monosaccharides 807:821 arg1 galactose 862:870 galactose 862:870 galactose 862:870 LBP-d was composed of eight kinds of monosaccharides (fucose, ribose, rhamnose, arabinose, xylose, mannose, galactose, and glucose), while LBP-e was composed of six kinds of monosaccharides (fucose, rhamnose, arabinose, mannose, galactose, and glucose). 26563650 5 41 dep monosaccharides 807:821 arg1 rhamnose 832:839 rhamnose 832:839 rhamnose 832:839 LBP-d was composed of eight kinds of monosaccharides (fucose, ribose, rhamnose, arabinose, xylose, mannose, galactose, and glucose), while LBP-e was composed of six kinds of monosaccharides (fucose, rhamnose, arabinose, mannose, galactose, and glucose). 26563650 5 41 dep monosaccharides 807:821 arg1 arabinose 842:850 arabinose 842:850 arabinose 842:850 LBP-d was composed of eight kinds of monosaccharides (fucose, ribose, rhamnose, arabinose, xylose, mannose, galactose, and glucose), while LBP-e was composed of six kinds of monosaccharides (fucose, rhamnose, arabinose, mannose, galactose, and glucose). 26563650 5 41 dep monosaccharides 807:821 arg1 glucose 877:883 glucose 877:883 glucose 877:883 LBP-d was composed of eight kinds of monosaccharides (fucose, ribose, rhamnose, arabinose, xylose, mannose, galactose, and glucose), while LBP-e was composed of six kinds of monosaccharides (fucose, rhamnose, arabinose, mannose, galactose, and glucose). 26563650 5 41 dep monosaccharides 807:821 arg1 monosaccharides 807:821 monosaccharides 807:821 monosaccharides (fucose, rhamnose, arabinose, mannose, galactose, and glucose) 807:884 LBP-d was composed of eight kinds of monosaccharides (fucose, ribose, rhamnose, arabinose, xylose, mannose, galactose, and glucose), while LBP-e was composed of six kinds of monosaccharides (fucose, rhamnose, arabinose, mannose, galactose, and glucose). 26563650 5 41 dep monosaccharides 807:821 arg1 fucose 824:829 fucose 824:829 fucose 824:829 LBP-d was composed of eight kinds of monosaccharides (fucose, ribose, rhamnose, arabinose, xylose, mannose, galactose, and glucose), while LBP-e was composed of six kinds of monosaccharides (fucose, rhamnose, arabinose, mannose, galactose, and glucose). 26563650 1 42 theme barbarum 136:143 arg1 polysaccharide 145:158 BACKGROUND Lycium barbarum polysaccharide 118:158 BACKGROUND Lycium barbarum polysaccharide (LBP) 118:164 BACKGROUND Lycium barbarum polysaccharide (LBP) is a natural functional component that has a variety of biological activities. 26563650 1 42 theme barbarum 136:143 arg1 component 190:198 a natural functional component 169:198 a natural functional component that has a variety of biological activities 169:242 BACKGROUND Lycium barbarum polysaccharide (LBP) is a natural functional component that has a variety of biological activities. 26563650 1 42 theme barbarum 136:143 arg1 LBP 161:163 LBP 161:163 LBP 161:163 BACKGROUND Lycium barbarum polysaccharide (LBP) is a natural functional component that has a variety of biological activities. 26563650 7 43 theme acid 1128:1131 arg1 higher 1167:1172 higher 1167:1172 higher 1167:1172 CONCLUSION The contents of protein, uronic acid, and galactose in LBP-e were much higher than those in LBP-d, which might responsible for their different bioactivities. 26563650 7 43 theme acid 1128:1131 arg1 contents 1100:1107 The contents 1096:1107 The contents of protein, uronic acid, and galactose in LBP-e 1096:1155 CONCLUSION The contents of protein, uronic acid, and galactose in LBP-e were much higher than those in LBP-d, which might responsible for their different bioactivities. 26563650 6 44 with phases 946:951 arg1 ratio 972:976 an inhibition ratio 958:976 an inhibition ratio of 26.70 and 45.13%, respectively 958:1010 LBP-d and LBP-e blocked SMMC-7721 cells at the G0/G1 and S phases with an inhibition ratio of 26.70 and 45.13%, respectively, and enhanced the concentration of Ca(2+) in the cytoplasm of SMMC-7721. 26563650 2 45 theme apoptosis-inducing 274:291 arg1 activities 293:302 apoptosis-inducing activities 274:302 apoptosis-inducing activities 274:302 The molecular structures and apoptosis-inducing activities on human hepatoma SMMC-7721 cells of two LBP fractions, LBP-d and LBP-e, were investigated. 26563650 2 46 theme fractions 349:357 arg1 structures 259:268 molecular structures 249:268 molecular structures 249:268 The molecular structures and apoptosis-inducing activities on human hepatoma SMMC-7721 cells of two LBP fractions, LBP-d and LBP-e, were investigated. 26563650 2 46 theme fractions 349:357 arg1 activities 293:302 apoptosis-inducing activities 274:302 apoptosis-inducing activities 274:302 The molecular structures and apoptosis-inducing activities on human hepatoma SMMC-7721 cells of two LBP fractions, LBP-d and LBP-e, were investigated. 26563650 2 47 from activities 293:302 arg1 cells 332:336 human hepatoma SMMC-7721 cells 307:336 human hepatoma SMMC-7721 cells 307:336 The molecular structures and apoptosis-inducing activities on human hepatoma SMMC-7721 cells of two LBP fractions, LBP-d and LBP-e, were investigated. 26563650 1 48 theme biological 222:231 arg1 activities 233:242 biological activities 222:242 biological activities 222:242 BACKGROUND Lycium barbarum polysaccharide (LBP) is a natural functional component that has a variety of biological activities. 26563650 7 49 from contents 1100:1107 arg1 LBP-e 1151:1155 LBP-e 1151:1155 LBP-e 1151:1155 CONCLUSION The contents of protein, uronic acid, and galactose in LBP-e were much higher than those in LBP-d, which might responsible for their different bioactivities. 26563650 6 50 theme SMMC-7721 1074:1082 arg1 cytoplasm 1061:1069 the cytoplasm 1057:1069 the cytoplasm of SMMC-7721 1057:1082 LBP-d and LBP-e blocked SMMC-7721 cells at the G0/G1 and S phases with an inhibition ratio of 26.70 and 45.13%, respectively, and enhanced the concentration of Ca(2+) in the cytoplasm of SMMC-7721. 26563650 2 51 theme LBP 345:347 arg1 LBP-e 370:374 LBP-e 370:374 LBP-e 370:374 The molecular structures and apoptosis-inducing activities on human hepatoma SMMC-7721 cells of two LBP fractions, LBP-d and LBP-e, were investigated. 26563650 2 51 theme LBP 345:347 arg1 LBP-d 360:364 LBP-d 360:364 LBP-d 360:364 The molecular structures and apoptosis-inducing activities on human hepatoma SMMC-7721 cells of two LBP fractions, LBP-d and LBP-e, were investigated. 26563650 2 51 theme LBP 345:347 arg1 fractions 349:357 two LBP fractions 341:357 two LBP fractions 341:357 The molecular structures and apoptosis-inducing activities on human hepatoma SMMC-7721 cells of two LBP fractions, LBP-d and LBP-e, were investigated. 26563650 1 52 theme activities 233:242 arg1 variety 211:217 a variety 209:217 a variety of biological activities 209:242 BACKGROUND Lycium barbarum polysaccharide (LBP) is a natural functional component that has a variety of biological activities. 26563650 1 52 theme activities 233:242 arg1 activities 233:242 biological activities 222:242 biological activities 222:242 BACKGROUND Lycium barbarum polysaccharide (LBP) is a natural functional component that has a variety of biological activities. 26563650 1 53 contain has 205:207 arg1 component 190:198 a natural functional component 169:198 a natural functional component that has a variety of biological activities 169:242 BACKGROUND Lycium barbarum polysaccharide (LBP) is a natural functional component that has a variety of biological activities. 26563650 1 53 contain has 205:207 arg1 polysaccharide 145:158 BACKGROUND Lycium barbarum polysaccharide 118:158 BACKGROUND Lycium barbarum polysaccharide (LBP) 118:164 BACKGROUND Lycium barbarum polysaccharide (LBP) is a natural functional component that has a variety of biological activities. 26563650 1 53 contain has 205:207 arg2 variety 211:217 a variety 209:217 a variety of biological activities 209:242 BACKGROUND Lycium barbarum polysaccharide (LBP) is a natural functional component that has a variety of biological activities. 26563650 1 53 contain has 205:207 arg2 activities 233:242 biological activities 222:242 biological activities 222:242 BACKGROUND Lycium barbarum polysaccharide (LBP) is a natural functional component that has a variety of biological activities. 26563650 3 54 theme different 504:512 arg1 proportions 514:524 different proportions 504:524 different proportions 504:524 RESULTS The results showed that LBP-d and LBP-e both consist of protein, uronic acid, and neutral sugars in different proportions. 26563650 5 55 theme monosaccharides 807:821 arg1 kinds 798:802 six kinds 794:802 six kinds of monosaccharides (fucose, rhamnose, arabinose, mannose, galactose, and glucose) 794:884 LBP-d was composed of eight kinds of monosaccharides (fucose, ribose, rhamnose, arabinose, xylose, mannose, galactose, and glucose), while LBP-e was composed of six kinds of monosaccharides (fucose, rhamnose, arabinose, mannose, galactose, and glucose). 26563650 4 56 theme Smith 614:618 arg1 degradation 620:630 Smith degradation 614:630 Smith degradation 614:630 The structure of LBP was characterized by gas chromatography, periodate oxidation, and Smith degradation. 26563650 6 57 theme SMMC-7721 911:919 arg1 cells 921:925 SMMC-7721 cells 911:925 SMMC-7721 cells 911:925 LBP-d and LBP-e blocked SMMC-7721 cells at the G0/G1 and S phases with an inhibition ratio of 26.70 and 45.13%, respectively, and enhanced the concentration of Ca(2+) in the cytoplasm of SMMC-7721. 26563650 2 58 theme molecular 249:257 arg1 structures 259:268 molecular structures 249:268 molecular structures 249:268 The molecular structures and apoptosis-inducing activities on human hepatoma SMMC-7721 cells of two LBP fractions, LBP-d and LBP-e, were investigated. 26563650 6 59 theme S 944:944 arg1 phases 946:951 the G0/G1 and S phases 930:951 phases 946:951 LBP-d and LBP-e blocked SMMC-7721 cells at the G0/G1 and S phases with an inhibition ratio of 26.70 and 45.13%, respectively, and enhanced the concentration of Ca(2+) in the cytoplasm of SMMC-7721. 26563650 7 60 theme protein 1112:1118 arg1 higher 1167:1172 higher 1167:1172 higher 1167:1172 CONCLUSION The contents of protein, uronic acid, and galactose in LBP-e were much higher than those in LBP-d, which might responsible for their different bioactivities. 26563650 7 60 theme protein 1112:1118 arg1 contents 1100:1107 The contents 1096:1107 The contents of protein, uronic acid, and galactose in LBP-e 1096:1155 CONCLUSION The contents of protein, uronic acid, and galactose in LBP-e were much higher than those in LBP-d, which might responsible for their different bioactivities. 24795711 5 0 theme Porcine 520:526 arg1 isolates 537:544 Porcine clinical isolates 520:544 Porcine clinical isolates 520:544 Porcine clinical isolates formed significantly more biofilm than the porcine commensal isolates. 24795711 8 1 theme low 865:867 arg1 doses 869:873 low doses 865:873 low doses of some of these antimicrobials 865:905 Exposure to low doses of some of these antimicrobials tended to lead to a diminution of the biofilm formed. 24795711 9 2 theme few 972:974 arg1 isolates 976:983 a few isolates 970:983 a few isolates 970:983 However, a few isolates showed an increase in biofilm formation when exposed to low doses of tylosin, bacitracin, virginiamycin, and monensin. 24795711 11 3 theme bacitracin 1268:1277 arg1 doses 1259:1263 low doses 1255:1263 low doses of bacitracin 1255:1277 Of those, four produced more biofilm in presence of low doses of bacitracin whereas biofilms formed without bacitracin were thinner and less elevated. 24795711 5 4 theme porcine 589:595 arg1 isolates 607:614 the porcine commensal isolates 585:614 the porcine commensal isolates 585:614 Porcine clinical isolates formed significantly more biofilm than the porcine commensal isolates. 24795711 8 5 theme some 878:881 arg1 doses 869:873 low doses 865:873 low doses of some of these antimicrobials 865:905 Exposure to low doses of some of these antimicrobials tended to lead to a diminution of the biofilm formed. 24795711 12 6 theme isolates 1497:1504 arg1 majority 1485:1492 the majority 1481:1492 the majority of isolates 1481:1504 An increase in the area occupied by bacteria in the biofilm following exposure to low doses of bacitracin was also observed in the majority of isolates. 24795711 13 7 with biofilms 1544:1551 arg1 exception 1562:1570 the exception 1558:1570 the exception of one isolate 1558:1585 Morphology examination revealed flat biofilms with the exception of one isolate that demonstrated a mushroom-like biofilm. 24795711 9 8 from increase 995:1002 arg1 formation 1015:1023 biofilm formation 1007:1023 biofilm formation 1007:1023 However, a few isolates showed an increase in biofilm formation when exposed to low doses of tylosin, bacitracin, virginiamycin, and monensin. 24795711 11 9 theme low 1255:1257 arg1 doses 1259:1263 low doses 1255:1263 low doses of bacitracin 1255:1277 Of those, four produced more biofilm in presence of low doses of bacitracin whereas biofilms formed without bacitracin were thinner and less elevated. 24795711 5 10 theme commensal 597:605 arg1 isolates 607:614 the porcine commensal isolates 585:614 the porcine commensal isolates 585:614 Porcine clinical isolates formed significantly more biofilm than the porcine commensal isolates. 24795711 13 11 theme isolate 1579:1585 arg1 exception 1562:1570 the exception 1558:1570 the exception of one isolate 1558:1585 Morphology examination revealed flat biofilms with the exception of one isolate that demonstrated a mushroom-like biofilm. 24795711 6 12 dep C. 654:655 arg1 perfringens 657:667 perfringens 657:667 perfringens 657:667 A subgroup of clinical and commensal C. perfringens isolates was randomly selected for further characterization. 24795711 14 13 theme DNA 1741:1743 arg1 presence 1669:1676 the presence 1665:1676 the presence of proteins, beta-1,4 linked polysaccharides and extracellular DNA 1665:1743 Matrix composition analysis showed the presence of proteins, beta-1,4 linked polysaccharides and extracellular DNA, but no poly-beta-1,6-N-acetyl-D-glucosamine. 24795711 2 14 theme inhibitory 313:322 arg1 concentrations 324:337 subminimal inhibitory concentrations 302:337 subminimal inhibitory concentrations of antimicrobials 302:355 Very little is known on the biofilm of C. perfringens and its exposure to subminimal inhibitory concentrations of antimicrobials. 24795711 14 15 theme Matrix 1630:1635 arg1 analysis 1649:1656 Matrix composition analysis 1630:1656 Matrix composition analysis 1630:1656 Matrix composition analysis showed the presence of proteins, beta-1,4 linked polysaccharides and extracellular DNA, but no poly-beta-1,6-N-acetyl-D-glucosamine. 24795711 9 16 theme monensin 1094:1101 arg1 doses 1045:1049 low doses 1041:1049 low doses of tylosin, bacitracin, virginiamycin, and monensin 1041:1101 However, a few isolates showed an increase in biofilm formation when exposed to low doses of tylosin, bacitracin, virginiamycin, and monensin. 24795711 9 17 theme low 1041:1043 arg1 doses 1045:1049 low doses 1041:1049 low doses of tylosin, bacitracin, virginiamycin, and monensin 1041:1101 However, a few isolates showed an increase in biofilm formation when exposed to low doses of tylosin, bacitracin, virginiamycin, and monensin. 24795711 2 18 theme perfringens 270:280 arg1 biofilm 256:262 the biofilm 252:262 the biofilm of C. perfringens 252:280 Very little is known on the biofilm of C. perfringens and its exposure to subminimal inhibitory concentrations of antimicrobials. 24795711 2 18 theme perfringens 270:280 arg1 exposure 290:297 its exposure 286:297 its exposure to subminimal inhibitory concentrations of antimicrobials 286:355 Very little is known on the biofilm of C. perfringens and its exposure to subminimal inhibitory concentrations of antimicrobials. 24795711 9 19 theme bacitracin 1063:1072 arg1 doses 1045:1049 low doses 1041:1049 low doses of tylosin, bacitracin, virginiamycin, and monensin 1041:1101 However, a few isolates showed an increase in biofilm formation when exposed to low doses of tylosin, bacitracin, virginiamycin, and monensin. 24795711 10 20 theme laser 1176:1180 arg1 microscopy 1191:1200 scanning laser confocal microscopy 1167:1200 scanning laser confocal microscopy 1167:1200 Six isolates were randomly selected for biofilm analysis using scanning laser confocal microscopy. 24795711 11 21 dep doses 1259:1263 arg1 presence 1243:1250 presence 1243:1250 presence 1243:1250 Of those, four produced more biofilm in presence of low doses of bacitracin whereas biofilms formed without bacitracin were thinner and less elevated. 24795711 15 22 theme antimicrobials 1900:1913 arg1 doses 1891:1895 low doses 1887:1895 low doses of antimicrobials 1887:1913 This study brings new information on the biofilm produced by C. perfringens and its exposure to low doses of antimicrobials. 24795711 5 23 theme more 567:570 arg1 biofilm 572:578 significantly more biofilm 553:578 significantly more biofilm 553:578 Porcine clinical isolates formed significantly more biofilm than the porcine commensal isolates. 24795711 2 24 theme C. 267:268 arg1 perfringens 270:280 C. perfringens 267:280 C. perfringens 267:280 Very little is known on the biofilm of C. perfringens and its exposure to subminimal inhibitory concentrations of antimicrobials. 24795711 6 25 theme further 704:710 arg1 characterization 712:727 further characterization 704:727 further characterization 704:727 A subgroup of clinical and commensal C. perfringens isolates was randomly selected for further characterization. 24795711 14 26 theme composition 1637:1647 arg1 analysis 1649:1656 Matrix composition analysis 1630:1656 Matrix composition analysis 1630:1656 Matrix composition analysis showed the presence of proteins, beta-1,4 linked polysaccharides and extracellular DNA, but no poly-beta-1,6-N-acetyl-D-glucosamine. 24795711 1 27 theme Clostridium 90:100 arg1 perfringens 102:112 Clostridium perfringens 90:112 Clostridium perfringens 90:112 Clostridium perfringens is an opportunistic pathogen that can cause food poisoning in humans and various enterotoxemia in animal species. 24795711 1 27 theme Clostridium 90:100 arg1 pathogen 134:141 an opportunistic pathogen 117:141 an opportunistic pathogen that can cause food poisoning in humans and various enterotoxemia in animal species 117:225 Clostridium perfringens is an opportunistic pathogen that can cause food poisoning in humans and various enterotoxemia in animal species. 24795711 9 28 theme virginiamycin 1075:1087 arg1 doses 1045:1049 low doses 1041:1049 low doses of tylosin, bacitracin, virginiamycin, and monensin 1041:1101 However, a few isolates showed an increase in biofilm formation when exposed to low doses of tylosin, bacitracin, virginiamycin, and monensin. 24795711 1 29 theme various 187:193 arg1 enterotoxemia 195:207 various enterotoxemia 187:207 various enterotoxemia in animal species 187:225 Clostridium perfringens is an opportunistic pathogen that can cause food poisoning in humans and various enterotoxemia in animal species. 24795711 0 30 theme Biofilm 0:6 arg1 formation 8:16 Biofilm formation 0:16 Biofilm formation of Clostridium perfringens 0:43 Biofilm formation of Clostridium perfringens and its exposure to low-dose antimicrobials. 24795711 2 31 theme subminimal 302:311 arg1 concentrations 324:337 subminimal inhibitory concentrations 302:337 subminimal inhibitory concentrations of antimicrobials 302:355 Very little is known on the biofilm of C. perfringens and its exposure to subminimal inhibitory concentrations of antimicrobials. 24795711 15 32 theme new 1809:1811 arg1 information 1813:1823 new information 1809:1823 new information on the biofilm produced by C. perfringens 1809:1865 This study brings new information on the biofilm produced by C. perfringens and its exposure to low doses of antimicrobials. 24795711 7 33 dep C. 759:760 arg1 perfringens 762:772 perfringens 762:772 perfringens 762:772 Biofilm was found to protect C. perfringens bacterial cells from exposure to high concentrations of tested antimicrobials. 24795711 0 34 theme Clostridium 21:31 arg1 perfringens 33:43 Clostridium perfringens 21:43 Clostridium perfringens 21:43 Biofilm formation of Clostridium perfringens and its exposure to low-dose antimicrobials. 24795711 7 35 theme tested 830:835 arg1 antimicrobials 837:850 tested antimicrobials 830:850 tested antimicrobials 830:850 Biofilm was found to protect C. perfringens bacterial cells from exposure to high concentrations of tested antimicrobials. 24795711 15 36 from information 1813:1823 arg1 biofilm 1832:1838 the biofilm 1828:1838 the biofilm produced by C. perfringens 1828:1865 This study brings new information on the biofilm produced by C. perfringens and its exposure to low doses of antimicrobials. 24795711 1 37 from poisoning 163:171 arg1 humans 176:181 humans 176:181 humans 176:181 Clostridium perfringens is an opportunistic pathogen that can cause food poisoning in humans and various enterotoxemia in animal species. 24795711 1 37 from poisoning 163:171 arg1 species 219:225 animal species 212:225 animal species 212:225 Clostridium perfringens is an opportunistic pathogen that can cause food poisoning in humans and various enterotoxemia in animal species. 24795711 14 38 theme polysaccharides 1707:1721 arg1 presence 1669:1676 the presence 1665:1676 the presence of proteins, beta-1,4 linked polysaccharides and extracellular DNA 1665:1743 Matrix composition analysis showed the presence of proteins, beta-1,4 linked polysaccharides and extracellular DNA, but no poly-beta-1,6-N-acetyl-D-glucosamine. 24795711 7 39 theme high 807:810 arg1 concentrations 812:825 high concentrations 807:825 high concentrations of tested antimicrobials 807:850 Biofilm was found to protect C. perfringens bacterial cells from exposure to high concentrations of tested antimicrobials. 24795711 11 40 theme more 1227:1230 arg1 biofilm 1232:1238 more biofilm 1227:1238 more biofilm 1227:1238 Of those, four produced more biofilm in presence of low doses of bacitracin whereas biofilms formed without bacitracin were thinner and less elevated. 24795711 12 41 from increase 1357:1364 arg1 area 1373:1376 the area 1369:1376 the area occupied by bacteria in the biofilm following exposure to low doses of bacitracin 1369:1458 An increase in the area occupied by bacteria in the biofilm following exposure to low doses of bacitracin was also observed in the majority of isolates. 24795711 7 42 theme antimicrobials 837:850 arg1 concentrations 812:825 high concentrations 807:825 high concentrations of tested antimicrobials 807:850 Biofilm was found to protect C. perfringens bacterial cells from exposure to high concentrations of tested antimicrobials. 24795711 1 43 theme animal 212:217 arg1 species 219:225 animal species 212:225 animal species 212:225 Clostridium perfringens is an opportunistic pathogen that can cause food poisoning in humans and various enterotoxemia in animal species. 24795711 14 44 theme proteins 1681:1688 arg1 presence 1669:1676 the presence 1665:1676 the presence of proteins, beta-1,4 linked polysaccharides and extracellular DNA 1665:1743 Matrix composition analysis showed the presence of proteins, beta-1,4 linked polysaccharides and extracellular DNA, but no poly-beta-1,6-N-acetyl-D-glucosamine. 24795711 4 45 theme animal 446:451 arg1 isolates 453:460 the C. perfringens human and animal isolates 417:460 the C. perfringens human and animal isolates tested in this study 417:481 Most of the C. perfringens human and animal isolates tested in this study were able to form biofilm (230/277). 24795711 14 46 link linked 1700:1705 arg1 polysaccharides 1707:1721 beta-1,4 linked polysaccharides 1691:1721 beta-1,4 linked polysaccharides 1691:1721 Matrix composition analysis showed the presence of proteins, beta-1,4 linked polysaccharides and extracellular DNA, but no poly-beta-1,6-N-acetyl-D-glucosamine. 24795711 6 47 theme isolates 669:676 arg1 subgroup 619:626 A subgroup 617:626 A subgroup of clinical and commensal C. perfringens isolates 617:676 A subgroup of clinical and commensal C. perfringens isolates was randomly selected for further characterization. 24795711 0 48 theme perfringens 33:43 arg1 formation 8:16 Biofilm formation 0:16 Biofilm formation of Clostridium perfringens 0:43 Biofilm formation of Clostridium perfringens and its exposure to low-dose antimicrobials. 24795711 0 48 theme perfringens 33:43 arg1 exposure 53:60 its exposure 49:60 its exposure to low-dose antimicrobials 49:87 Biofilm formation of Clostridium perfringens and its exposure to low-dose antimicrobials. 24795711 14 49 theme extracellular 1727:1739 arg1 DNA 1741:1743 extracellular DNA 1727:1743 extracellular DNA 1727:1743 Matrix composition analysis showed the presence of proteins, beta-1,4 linked polysaccharides and extracellular DNA, but no poly-beta-1,6-N-acetyl-D-glucosamine. 24795711 13 50 theme flat 1539:1542 arg1 biofilms 1544:1551 flat biofilms 1539:1551 flat biofilms with the exception of one isolate that demonstrated a mushroom-like biofilm 1539:1627 Morphology examination revealed flat biofilms with the exception of one isolate that demonstrated a mushroom-like biofilm. 24795711 5 51 theme clinical 528:535 arg1 isolates 537:544 Porcine clinical isolates 520:544 Porcine clinical isolates 520:544 Porcine clinical isolates formed significantly more biofilm than the porcine commensal isolates. 24795711 15 52 theme C. 1852:1853 arg1 perfringens 1855:1865 C. perfringens 1852:1865 C. perfringens 1852:1865 This study brings new information on the biofilm produced by C. perfringens and its exposure to low doses of antimicrobials. 24795711 10 53 theme biofilm 1144:1150 arg1 analysis 1152:1159 biofilm analysis 1144:1159 biofilm analysis using scanning laser confocal microscopy 1144:1200 Six isolates were randomly selected for biofilm analysis using scanning laser confocal microscopy. 24795711 13 54 theme mushroom-like 1607:1619 arg1 biofilm 1621:1627 a mushroom-like biofilm 1605:1627 a mushroom-like biofilm 1605:1627 Morphology examination revealed flat biofilms with the exception of one isolate that demonstrated a mushroom-like biofilm. 24795711 14 55 theme beta-1,4 1691:1698 arg1 polysaccharides 1707:1721 beta-1,4 linked polysaccharides 1691:1721 beta-1,4 linked polysaccharides 1691:1721 Matrix composition analysis showed the presence of proteins, beta-1,4 linked polysaccharides and extracellular DNA, but no poly-beta-1,6-N-acetyl-D-glucosamine. 24795711 14 56 theme linked 1700:1705 arg1 polysaccharides 1707:1721 beta-1,4 linked polysaccharides 1691:1721 beta-1,4 linked polysaccharides 1691:1721 Matrix composition analysis showed the presence of proteins, beta-1,4 linked polysaccharides and extracellular DNA, but no poly-beta-1,6-N-acetyl-D-glucosamine. 24795711 1 57 theme opportunistic 120:132 arg1 perfringens 102:112 Clostridium perfringens 90:112 Clostridium perfringens 90:112 Clostridium perfringens is an opportunistic pathogen that can cause food poisoning in humans and various enterotoxemia in animal species. 24795711 1 57 theme opportunistic 120:132 arg1 pathogen 134:141 an opportunistic pathogen 117:141 an opportunistic pathogen that can cause food poisoning in humans and various enterotoxemia in animal species 117:225 Clostridium perfringens is an opportunistic pathogen that can cause food poisoning in humans and various enterotoxemia in animal species. 24795711 9 58 theme biofilm 1007:1013 arg1 formation 1015:1023 biofilm formation 1007:1023 biofilm formation 1007:1023 However, a few isolates showed an increase in biofilm formation when exposed to low doses of tylosin, bacitracin, virginiamycin, and monensin. 24795711 12 59 theme bacitracin 1449:1458 arg1 doses 1440:1444 low doses 1436:1444 low doses of bacitracin 1436:1458 An increase in the area occupied by bacteria in the biofilm following exposure to low doses of bacitracin was also observed in the majority of isolates. 24795711 8 60 theme biofilm 945:951 arg1 diminution 927:936 a diminution 925:936 a diminution of the biofilm formed 925:958 Exposure to low doses of some of these antimicrobials tended to lead to a diminution of the biofilm formed. 24795711 2 61 theme antimicrobials 342:355 arg1 concentrations 324:337 subminimal inhibitory concentrations 302:337 subminimal inhibitory concentrations of antimicrobials 302:355 Very little is known on the biofilm of C. perfringens and its exposure to subminimal inhibitory concentrations of antimicrobials. 24795711 9 62 theme tylosin 1054:1060 arg1 doses 1045:1049 low doses 1041:1049 low doses of tylosin, bacitracin, virginiamycin, and monensin 1041:1101 However, a few isolates showed an increase in biofilm formation when exposed to low doses of tylosin, bacitracin, virginiamycin, and monensin. 24795711 4 63 theme C. 421:422 arg1 isolates 453:460 the C. perfringens human and animal isolates 417:460 the C. perfringens human and animal isolates tested in this study 417:481 Most of the C. perfringens human and animal isolates tested in this study were able to form biofilm (230/277). 24795711 12 64 located observed 1469:1476 arg2 increase 1357:1364 An increase 1354:1364 An increase in the area occupied by bacteria in the biofilm following exposure to low doses of bacitracin 1354:1458 An increase in the area occupied by bacteria in the biofilm following exposure to low doses of bacitracin was also observed in the majority of isolates. 24795711 12 64 located observed 1469:1476 arg1 majority 1485:1492 the majority 1481:1492 the majority of isolates 1481:1504 An increase in the area occupied by bacteria in the biofilm following exposure to low doses of bacitracin was also observed in the majority of isolates. 24795711 6 65 theme C. 654:655 arg1 isolates 669:676 clinical and commensal C. perfringens isolates 631:676 clinical and commensal C. perfringens isolates 631:676 A subgroup of clinical and commensal C. perfringens isolates was randomly selected for further characterization. 24795711 10 66 theme confocal 1182:1189 arg1 microscopy 1191:1200 scanning laser confocal microscopy 1167:1200 scanning laser confocal microscopy 1167:1200 Six isolates were randomly selected for biofilm analysis using scanning laser confocal microscopy. 24795711 6 67 theme commensal 644:652 arg1 isolates 669:676 clinical and commensal C. perfringens isolates 631:676 clinical and commensal C. perfringens isolates 631:676 A subgroup of clinical and commensal C. perfringens isolates was randomly selected for further characterization. 24795711 7 68 theme bacterial 774:782 arg1 cells 784:788 C. perfringens bacterial cells 759:788 C. perfringens bacterial cells 759:788 Biofilm was found to protect C. perfringens bacterial cells from exposure to high concentrations of tested antimicrobials. 24795711 0 69 theme low-dose 65:72 arg1 antimicrobials 74:87 low-dose antimicrobials 65:87 low-dose antimicrobials 65:87 Biofilm formation of Clostridium perfringens and its exposure to low-dose antimicrobials. 24795711 4 70 theme human 436:440 arg1 isolates 453:460 the C. perfringens human and animal isolates 417:460 the C. perfringens human and animal isolates tested in this study 417:481 Most of the C. perfringens human and animal isolates tested in this study were able to form biofilm (230/277). 24795711 13 71 theme Morphology 1507:1516 arg1 examination 1518:1528 Morphology examination 1507:1528 Morphology examination 1507:1528 Morphology examination revealed flat biofilms with the exception of one isolate that demonstrated a mushroom-like biofilm. 24795711 1 72 from enterotoxemia 195:207 arg1 humans 176:181 humans 176:181 humans 176:181 Clostridium perfringens is an opportunistic pathogen that can cause food poisoning in humans and various enterotoxemia in animal species. 24795711 1 72 from enterotoxemia 195:207 arg1 species 219:225 animal species 212:225 animal species 212:225 Clostridium perfringens is an opportunistic pathogen that can cause food poisoning in humans and various enterotoxemia in animal species. 24795711 15 73 from exposure 1875:1882 arg1 biofilm 1832:1838 the biofilm 1828:1838 the biofilm produced by C. perfringens 1828:1865 This study brings new information on the biofilm produced by C. perfringens and its exposure to low doses of antimicrobials. 24795711 10 74 theme scanning 1167:1174 arg1 microscopy 1191:1200 scanning laser confocal microscopy 1167:1200 scanning laser confocal microscopy 1167:1200 Six isolates were randomly selected for biofilm analysis using scanning laser confocal microscopy. 24795711 15 75 theme low 1887:1889 arg1 doses 1891:1895 low doses 1887:1895 low doses of antimicrobials 1887:1913 This study brings new information on the biofilm produced by C. perfringens and its exposure to low doses of antimicrobials. 24795711 12 76 theme low 1436:1438 arg1 doses 1440:1444 low doses 1436:1444 low doses of bacitracin 1436:1458 An increase in the area occupied by bacteria in the biofilm following exposure to low doses of bacitracin was also observed in the majority of isolates. 24795711 7 77 theme C. 759:760 arg1 cells 784:788 C. perfringens bacterial cells 759:788 C. perfringens bacterial cells 759:788 Biofilm was found to protect C. perfringens bacterial cells from exposure to high concentrations of tested antimicrobials. 24795711 1 78 theme food 158:161 arg1 poisoning 163:171 food poisoning 158:171 food poisoning in humans 158:181 Clostridium perfringens is an opportunistic pathogen that can cause food poisoning in humans and various enterotoxemia in animal species. 24795711 6 79 theme clinical 631:638 arg1 isolates 669:676 clinical and commensal C. perfringens isolates 631:676 clinical and commensal C. perfringens isolates 631:676 A subgroup of clinical and commensal C. perfringens isolates was randomly selected for further characterization. 24795711 4 80 dep C. 421:422 arg1 perfringens 424:434 perfringens 424:434 perfringens 424:434 Most of the C. perfringens human and animal isolates tested in this study were able to form biofilm (230/277). 27320609 9 0 theme glycans 1249:1255 arg1 structures 1231:1240 the structures 1227:1240 the structures of the glycans 1227:1255 The detected N-glycan peaks in the LC-MS spectra were selected using the FLexAnalysis software program and the structures of the glycans were predicted using the GlyocoMod Tool. 27320609 9 1 theme N-glycan 1133:1140 arg1 peaks 1142:1146 The detected N-glycan peaks 1120:1146 The detected N-glycan peaks in the LC-MS spectra 1120:1167 The detected N-glycan peaks in the LC-MS spectra were selected using the FLexAnalysis software program and the structures of the glycans were predicted using the GlyocoMod Tool. 27320609 1 2 theme sources 125:131 arg1 sources 125:131 the most suitable sources 107:131 the most suitable sources of islets for clinical xenotransplantation 107:174 The pig pancreas is considered to be one of the most suitable sources of islets for clinical xenotransplantation. 27320609 1 2 theme sources 125:131 arg1 one 100:102 one 100:102 one 100:102 The pig pancreas is considered to be one of the most suitable sources of islets for clinical xenotransplantation. 27320609 1 2 theme sources 125:131 arg1 pancreas 71:78 The pig pancreas 63:78 The pig pancreas 63:78 The pig pancreas is considered to be one of the most suitable sources of islets for clinical xenotransplantation. 27320609 11 3 theme sulfate 1481:1487 arg1 structures 1489:1498 sulfate structures 1481:1498 sulfate structures 1481:1498 Among them, 5 sulfated glycans were estimated, confirming the existence of sulfate structures in N-glycans in API. 27320609 4 4 theme many 552:555 arg1 studies 557:563 many studies 552:563 many studies related to glycoproteins and glycolipids 552:604 Concerning the so-called non-Gal epitopes, many studies related to glycoproteins and glycolipids are ongoing in efforts to identify them. 27320609 6 5 attach isolated 753:760 arg2 N-glycans 738:746 N-glycans 738:746 N-glycans 738:746 In our previous study, N-glycans were isolated from APIs, and the structures of 28 of the N-glycans were detected. 27320609 6 5 attach isolated 753:760 arg1 APIs 767:770 APIs 767:770 APIs 767:770 In our previous study, N-glycans were isolated from APIs, and the structures of 28 of the N-glycans were detected. 27320609 11 6 from existence 1468:1476 arg1 N-glycans 1503:1511 N-glycans 1503:1511 N-glycans 1503:1511 Among them, 5 sulfated glycans were estimated, confirming the existence of sulfate structures in N-glycans in API. 27320609 0 7 link N-linked 26:33 arg1 Sugars 35:40 N-linked Sugars 26:40 N-linked Sugars in Adult Pig Islets 26:60 Supplemental Analysis for N-linked Sugars in Adult Pig Islets. 27320609 3 8 theme clear 474:478 arg1 antigenicity 480:491 a clear antigenicity 472:491 a clear antigenicity to human serum 472:506 Wild-type adult pig islets (APIs) that originally produced negligible levels of α-Gal, different from neonatal porcine islet-like cell clusters, showed a clear antigenicity to human serum. 27320609 3 9 theme pig 336:338 arg1 APIs 348:351 APIs 348:351 APIs 348:351 Wild-type adult pig islets (APIs) that originally produced negligible levels of α-Gal, different from neonatal porcine islet-like cell clusters, showed a clear antigenicity to human serum. 27320609 3 9 theme pig 336:338 arg1 islets 340:345 Wild-type adult pig islets 320:345 Wild-type adult pig islets (APIs) 320:352 Wild-type adult pig islets (APIs) that originally produced negligible levels of α-Gal, different from neonatal porcine islet-like cell clusters, showed a clear antigenicity to human serum. 27320609 12 10 contain contain 1593:1599 arg2 units 1617:1621 two deoxyhexose units 1601:1621 two deoxyhexose units 1601:1621 In addition, these data may supplement several N-glycan structures that contain two deoxyhexose units, such as fucose, to our previous report. 27320609 12 10 contain contain 1593:1599 arg1 structures 1577:1586 several N-glycan structures 1560:1586 several N-glycan structures that contain two deoxyhexose units, such as fucose, to our previous report 1560:1661 In addition, these data may supplement several N-glycan structures that contain two deoxyhexose units, such as fucose, to our previous report. 27320609 7 11 theme chromatography-mass 922:940 arg1 LC-MS 956:960 LC-MS 956:960 LC-MS 956:960 In this study, to identify additional structures, further analyses were performed by liquid chromatography-mass spectrometry (LC-MS). 27320609 7 11 theme chromatography-mass 922:940 arg1 spectrometry 942:953 liquid chromatography-mass spectrometry 915:953 liquid chromatography-mass spectrometry (LC-MS) 915:961 In this study, to identify additional structures, further analyses were performed by liquid chromatography-mass spectrometry (LC-MS). 27320609 4 12 gly glycoproteins 576:588 arg1 glycoproteins 576:588 glycoproteins 576:588 glycoproteins 576:588 Concerning the so-called non-Gal epitopes, many studies related to glycoproteins and glycolipids are ongoing in efforts to identify them. 27320609 2 13 theme pigs 271:274 arg1 organs 255:260 the organs 251:260 the organs of these pigs 251:274 However, after producing α1-3galactosyltransferase knockout pigs, most of the organs of these pigs showed less antigenicity to the human body. 27320609 4 14 theme related 565:571 arg1 studies 557:563 many studies 552:563 many studies related to glycoproteins and glycolipids 552:604 Concerning the so-called non-Gal epitopes, many studies related to glycoproteins and glycolipids are ongoing in efforts to identify them. 27320609 13 15 theme antigenicity 1718:1729 arg1 studies 1707:1713 future studies 1700:1713 future studies of antigenicity associated with API 1700:1749 The data herein will be helpful for future studies of antigenicity associated with API. 27320609 10 16 theme API 1302:1304 arg1 preparation 1306:1316 The API preparation 1298:1316 The API preparation 1298:1316 The API preparation contained 11 peaks and 16 structures were then nominated as containing N-linked sugars. 27320609 8 17 theme Neil 1027:1030 arg1 et al 1032:1036 O'Neil et al 1025:1036 O'Neil et al with minor modifications 1025:1061 N-glycans were isolated from APIs by the method described by O'Neil et al with minor modifications and LC-MS-based structural analyses were then performed. 27320609 9 18 from peaks 1142:1146 arg1 spectra 1161:1167 the LC-MS spectra 1151:1167 the LC-MS spectra 1151:1167 The detected N-glycan peaks in the LC-MS spectra were selected using the FLexAnalysis software program and the structures of the glycans were predicted using the GlyocoMod Tool. 27320609 8 19 attach isolated 979:986 arg2 N-glycans 964:972 N-glycans 964:972 N-glycans 964:972 N-glycans were isolated from APIs by the method described by O'Neil et al with minor modifications and LC-MS-based structural analyses were then performed. 27320609 8 19 attach isolated 979:986 arg1 APIs 993:996 APIs 993:996 APIs 993:996 N-glycans were isolated from APIs by the method described by O'Neil et al with minor modifications and LC-MS-based structural analyses were then performed. 27320609 3 20 theme Wild-type 320:328 arg1 APIs 348:351 APIs 348:351 APIs 348:351 Wild-type adult pig islets (APIs) that originally produced negligible levels of α-Gal, different from neonatal porcine islet-like cell clusters, showed a clear antigenicity to human serum. 27320609 3 20 theme Wild-type 320:328 arg1 islets 340:345 Wild-type adult pig islets 320:345 Wild-type adult pig islets (APIs) 320:352 Wild-type adult pig islets (APIs) that originally produced negligible levels of α-Gal, different from neonatal porcine islet-like cell clusters, showed a clear antigenicity to human serum. 27320609 9 21 theme LC-MS 1155:1159 arg1 spectra 1161:1167 the LC-MS spectra 1151:1167 the LC-MS spectra 1151:1167 The detected N-glycan peaks in the LC-MS spectra were selected using the FLexAnalysis software program and the structures of the glycans were predicted using the GlyocoMod Tool. 27320609 3 22 theme human 496:500 arg1 serum 502:506 human serum 496:506 human serum 496:506 Wild-type adult pig islets (APIs) that originally produced negligible levels of α-Gal, different from neonatal porcine islet-like cell clusters, showed a clear antigenicity to human serum. 27320609 1 23 theme islets 136:141 arg1 sources 125:131 the most suitable sources 107:131 the most suitable sources of islets for clinical xenotransplantation 107:174 The pig pancreas is considered to be one of the most suitable sources of islets for clinical xenotransplantation. 27320609 3 24 theme adult 330:334 arg1 APIs 348:351 APIs 348:351 APIs 348:351 Wild-type adult pig islets (APIs) that originally produced negligible levels of α-Gal, different from neonatal porcine islet-like cell clusters, showed a clear antigenicity to human serum. 27320609 3 24 theme adult 330:334 arg1 islets 340:345 Wild-type adult pig islets 320:345 Wild-type adult pig islets (APIs) 320:352 Wild-type adult pig islets (APIs) that originally produced negligible levels of α-Gal, different from neonatal porcine islet-like cell clusters, showed a clear antigenicity to human serum. 27320609 9 25 theme GlyocoMod 1282:1290 arg1 Tool 1292:1295 the GlyocoMod Tool 1278:1295 the GlyocoMod Tool 1278:1295 The detected N-glycan peaks in the LC-MS spectra were selected using the FLexAnalysis software program and the structures of the glycans were predicted using the GlyocoMod Tool. 27320609 10 26 theme N-linked 1389:1396 arg1 sugars 1398:1403 N-linked sugars 1389:1403 N-linked sugars 1389:1403 The API preparation contained 11 peaks and 16 structures were then nominated as containing N-linked sugars. 27320609 1 27 theme pig 67:69 arg1 sources 125:131 the most suitable sources 107:131 the most suitable sources of islets for clinical xenotransplantation 107:174 The pig pancreas is considered to be one of the most suitable sources of islets for clinical xenotransplantation. 27320609 1 27 theme pig 67:69 arg1 one 100:102 one 100:102 one 100:102 The pig pancreas is considered to be one of the most suitable sources of islets for clinical xenotransplantation. 27320609 1 27 theme pig 67:69 arg1 pancreas 71:78 The pig pancreas 63:78 The pig pancreas 63:78 The pig pancreas is considered to be one of the most suitable sources of islets for clinical xenotransplantation. 27320609 3 28 theme different 407:415 arg1 levels 390:395 negligible levels 379:395 negligible levels 379:395 Wild-type adult pig islets (APIs) that originally produced negligible levels of α-Gal, different from neonatal porcine islet-like cell clusters, showed a clear antigenicity to human serum. 27320609 0 29 from Sugars 35:40 arg1 Islets 55:60 Adult Pig Islets 45:60 Adult Pig Islets 45:60 Supplemental Analysis for N-linked Sugars in Adult Pig Islets. 27320609 8 30 theme O' 1025:1026 arg1 et al 1032:1036 O'Neil et al 1025:1036 O'Neil et al with minor modifications 1025:1061 N-glycans were isolated from APIs by the method described by O'Neil et al with minor modifications and LC-MS-based structural analyses were then performed. 27320609 3 31 from clusters 455:462 arg1 different 407:415 different 407:415 different 407:415 Wild-type adult pig islets (APIs) that originally produced negligible levels of α-Gal, different from neonatal porcine islet-like cell clusters, showed a clear antigenicity to human serum. 27320609 1 32 theme clinical 147:154 arg1 xenotransplantation 156:174 clinical xenotransplantation 147:174 clinical xenotransplantation 147:174 The pig pancreas is considered to be one of the most suitable sources of islets for clinical xenotransplantation. 27320609 0 33 theme Supplemental 0:11 arg1 Analysis 13:20 Supplemental Analysis 0:20 Supplemental Analysis for N-linked Sugars in Adult Pig Islets 0:60 Supplemental Analysis for N-linked Sugars in Adult Pig Islets. 27320609 4 34 theme so-called 524:532 arg1 epitopes 542:549 the so-called non-Gal epitopes 520:549 the so-called non-Gal epitopes 520:549 Concerning the so-called non-Gal epitopes, many studies related to glycoproteins and glycolipids are ongoing in efforts to identify them. 27320609 4 35 from efforts 621:627 arg1 ongoing 610:616 ongoing 610:616 ongoing 610:616 Concerning the so-called non-Gal epitopes, many studies related to glycoproteins and glycolipids are ongoing in efforts to identify them. 27320609 3 36 theme α-Gal 400:404 arg1 levels 390:395 negligible levels 379:395 negligible levels 379:395 Wild-type adult pig islets (APIs) that originally produced negligible levels of α-Gal, different from neonatal porcine islet-like cell clusters, showed a clear antigenicity to human serum. 27320609 0 37 theme N-linked 26:33 arg1 Sugars 35:40 N-linked Sugars 26:40 N-linked Sugars in Adult Pig Islets 26:60 Supplemental Analysis for N-linked Sugars in Adult Pig Islets. 27320609 12 38 theme N-glycan 1568:1575 arg1 structures 1577:1586 several N-glycan structures 1560:1586 several N-glycan structures that contain two deoxyhexose units, such as fucose, to our previous report 1560:1661 In addition, these data may supplement several N-glycan structures that contain two deoxyhexose units, such as fucose, to our previous report. 27320609 7 39 theme further 880:886 arg1 analyses 888:895 further analyses 880:895 further analyses 880:895 In this study, to identify additional structures, further analyses were performed by liquid chromatography-mass spectrometry (LC-MS). 27320609 7 40 theme liquid 915:920 arg1 LC-MS 956:960 LC-MS 956:960 LC-MS 956:960 In this study, to identify additional structures, further analyses were performed by liquid chromatography-mass spectrometry (LC-MS). 27320609 7 40 theme liquid 915:920 arg1 spectrometry 942:953 liquid chromatography-mass spectrometry 915:953 liquid chromatography-mass spectrometry (LC-MS) 915:961 In this study, to identify additional structures, further analyses were performed by liquid chromatography-mass spectrometry (LC-MS). 27320609 3 41 theme porcine 431:437 arg1 clusters 455:462 neonatal porcine islet-like cell clusters 422:462 neonatal porcine islet-like cell clusters 422:462 Wild-type adult pig islets (APIs) that originally produced negligible levels of α-Gal, different from neonatal porcine islet-like cell clusters, showed a clear antigenicity to human serum. 27320609 5 42 theme non-Gal 673:679 arg1 glycoantigens 681:693 non-Gal glycoantigens 673:693 non-Gal glycoantigens 673:693 However, our knowledge of non-Gal glycoantigens remains incomplete. 27320609 4 43 from ongoing 610:616 arg1 efforts 621:627 efforts 621:627 efforts to identify them 621:644 Concerning the so-called non-Gal epitopes, many studies related to glycoproteins and glycolipids are ongoing in efforts to identify them. 27320609 3 44 theme islet-like 439:448 arg1 clusters 455:462 neonatal porcine islet-like cell clusters 422:462 neonatal porcine islet-like cell clusters 422:462 Wild-type adult pig islets (APIs) that originally produced negligible levels of α-Gal, different from neonatal porcine islet-like cell clusters, showed a clear antigenicity to human serum. 27320609 3 45 theme negligible 379:388 arg1 levels 390:395 negligible levels 379:395 negligible levels 379:395 Wild-type adult pig islets (APIs) that originally produced negligible levels of α-Gal, different from neonatal porcine islet-like cell clusters, showed a clear antigenicity to human serum. 27320609 4 46 theme non-Gal 534:540 arg1 epitopes 542:549 the so-called non-Gal epitopes 520:549 the so-called non-Gal epitopes 520:549 Concerning the so-called non-Gal epitopes, many studies related to glycoproteins and glycolipids are ongoing in efforts to identify them. 27320609 5 47 theme glycoantigens 681:693 arg1 knowledge 660:668 our knowledge 656:668 our knowledge of non-Gal glycoantigens 656:693 However, our knowledge of non-Gal glycoantigens remains incomplete. 27320609 9 48 theme FLexAnalysis 1193:1204 arg1 program 1215:1221 the FLexAnalysis software program 1189:1221 the FLexAnalysis software program 1189:1221 The detected N-glycan peaks in the LC-MS spectra were selected using the FLexAnalysis software program and the structures of the glycans were predicted using the GlyocoMod Tool. 27320609 4 49 dep efforts 621:627 arg1 identify 632:639 identify 632:639 to identify them 629:644 Concerning the so-called non-Gal epitopes, many studies related to glycoproteins and glycolipids are ongoing in efforts to identify them. 27320609 10 50 contain contained 1318:1326 arg2 peaks 1331:1335 11 peaks 1328:1335 11 peaks 1328:1335 The API preparation contained 11 peaks and 16 structures were then nominated as containing N-linked sugars. 27320609 10 50 contain contained 1318:1326 arg1 preparation 1306:1316 The API preparation 1298:1316 The API preparation 1298:1316 The API preparation contained 11 peaks and 16 structures were then nominated as containing N-linked sugars. 27320609 9 51 theme software 1206:1213 arg1 program 1215:1221 the FLexAnalysis software program 1189:1221 the FLexAnalysis software program 1189:1221 The detected N-glycan peaks in the LC-MS spectra were selected using the FLexAnalysis software program and the structures of the glycans were predicted using the GlyocoMod Tool. 27320609 2 52 theme knockout 228:235 arg1 pigs 237:240 α1-3galactosyltransferase knockout pigs 202:240 α1-3galactosyltransferase knockout pigs 202:240 However, after producing α1-3galactosyltransferase knockout pigs, most of the organs of these pigs showed less antigenicity to the human body. 27320609 3 53 theme neonatal 422:429 arg1 clusters 455:462 neonatal porcine islet-like cell clusters 422:462 neonatal porcine islet-like cell clusters 422:462 Wild-type adult pig islets (APIs) that originally produced negligible levels of α-Gal, different from neonatal porcine islet-like cell clusters, showed a clear antigenicity to human serum. 27320609 0 54 theme Pig 51:53 arg1 Islets 55:60 Adult Pig Islets 45:60 Adult Pig Islets 45:60 Supplemental Analysis for N-linked Sugars in Adult Pig Islets. 27320609 6 55 theme N-glycans 805:813 arg1 28 795:796 28 795:796 28 795:796 In our previous study, N-glycans were isolated from APIs, and the structures of 28 of the N-glycans were detected. 27320609 6 55 theme N-glycans 805:813 arg1 N-glycans 805:813 the N-glycans 801:813 the N-glycans 801:813 In our previous study, N-glycans were isolated from APIs, and the structures of 28 of the N-glycans were detected. 27320609 2 56 theme α1-3galactosyltransferase 202:226 arg1 pigs 237:240 α1-3galactosyltransferase knockout pigs 202:240 α1-3galactosyltransferase knockout pigs 202:240 However, after producing α1-3galactosyltransferase knockout pigs, most of the organs of these pigs showed less antigenicity to the human body. 27320609 8 57 theme structural 1079:1088 arg1 analyses 1090:1097 LC-MS-based structural analyses 1067:1097 LC-MS-based structural analyses 1067:1097 N-glycans were isolated from APIs by the method described by O'Neil et al with minor modifications and LC-MS-based structural analyses were then performed. 27320609 0 58 theme Adult 45:49 arg1 Islets 55:60 Adult Pig Islets 45:60 Adult Pig Islets 45:60 Supplemental Analysis for N-linked Sugars in Adult Pig Islets. 27320609 7 59 theme additional 857:866 arg1 structures 868:877 additional structures 857:877 additional structures 857:877 In this study, to identify additional structures, further analyses were performed by liquid chromatography-mass spectrometry (LC-MS). 27320609 8 60 theme minor 1043:1047 arg1 modifications 1049:1061 minor modifications 1043:1061 minor modifications 1043:1061 N-glycans were isolated from APIs by the method described by O'Neil et al with minor modifications and LC-MS-based structural analyses were then performed. 27320609 11 61 theme structures 1489:1498 arg1 existence 1468:1476 the existence 1464:1476 the existence of sulfate structures in N-glycans 1464:1511 Among them, 5 sulfated glycans were estimated, confirming the existence of sulfate structures in N-glycans in API. 27320609 6 62 theme previous 722:729 arg1 study 731:735 our previous study 718:735 our previous study 718:735 In our previous study, N-glycans were isolated from APIs, and the structures of 28 of the N-glycans were detected. 27320609 2 63 theme human 308:312 arg1 body 314:317 the human body 304:317 the human body 304:317 However, after producing α1-3galactosyltransferase knockout pigs, most of the organs of these pigs showed less antigenicity to the human body. 27320609 12 64 theme previous 1647:1654 arg1 report 1656:1661 our previous report 1643:1661 our previous report 1643:1661 In addition, these data may supplement several N-glycan structures that contain two deoxyhexose units, such as fucose, to our previous report. 27320609 8 65 theme LC-MS-based 1067:1077 arg1 analyses 1090:1097 LC-MS-based structural analyses 1067:1097 LC-MS-based structural analyses 1067:1097 N-glycans were isolated from APIs by the method described by O'Neil et al with minor modifications and LC-MS-based structural analyses were then performed. 27320609 6 66 theme 28 795:796 arg1 structures 781:790 the structures 777:790 the structures of 28 of the N-glycans 777:813 In our previous study, N-glycans were isolated from APIs, and the structures of 28 of the N-glycans were detected. 27320609 8 67 with et al 1032:1036 arg1 modifications 1049:1061 minor modifications 1043:1061 minor modifications 1043:1061 N-glycans were isolated from APIs by the method described by O'Neil et al with minor modifications and LC-MS-based structural analyses were then performed. 27320609 3 68 theme cell 450:453 arg1 clusters 455:462 neonatal porcine islet-like cell clusters 422:462 neonatal porcine islet-like cell clusters 422:462 Wild-type adult pig islets (APIs) that originally produced negligible levels of α-Gal, different from neonatal porcine islet-like cell clusters, showed a clear antigenicity to human serum. 27320609 12 69 theme several 1560:1566 arg1 structures 1577:1586 several N-glycan structures 1560:1586 several N-glycan structures that contain two deoxyhexose units, such as fucose, to our previous report 1560:1661 In addition, these data may supplement several N-glycan structures that contain two deoxyhexose units, such as fucose, to our previous report. 27320609 11 70 theme sulfated 1420:1427 arg1 glycans 1429:1435 5 sulfated glycans 1418:1435 5 sulfated glycans 1418:1435 Among them, 5 sulfated glycans were estimated, confirming the existence of sulfate structures in N-glycans in API. 27320609 10 71 link N-linked 1389:1396 arg1 sugars 1398:1403 N-linked sugars 1389:1403 N-linked sugars 1389:1403 The API preparation contained 11 peaks and 16 structures were then nominated as containing N-linked sugars. 27320609 12 72 theme deoxyhexose 1605:1615 arg1 units 1617:1621 two deoxyhexose units 1601:1621 two deoxyhexose units 1601:1621 In addition, these data may supplement several N-glycan structures that contain two deoxyhexose units, such as fucose, to our previous report. 27320609 9 73 theme detected 1124:1131 arg1 peaks 1142:1146 The detected N-glycan peaks 1120:1146 The detected N-glycan peaks in the LC-MS spectra 1120:1167 The detected N-glycan peaks in the LC-MS spectra were selected using the FLexAnalysis software program and the structures of the glycans were predicted using the GlyocoMod Tool. 27320609 1 74 theme suitable 116:123 arg1 sources 125:131 the most suitable sources 107:131 the most suitable sources of islets for clinical xenotransplantation 107:174 The pig pancreas is considered to be one of the most suitable sources of islets for clinical xenotransplantation. 27320609 13 75 theme future 1700:1705 arg1 studies 1707:1713 future studies 1700:1713 future studies of antigenicity associated with API 1700:1749 The data herein will be helpful for future studies of antigenicity associated with API. 27139251 2 0 theme pharmacokinetic 443:457 arg1 properties 459:468 improved pharmacokinetic properties 434:468 improved pharmacokinetic properties 434:468 As part of an on-going search for a pramlintide analogue with improved pharmacokinetic properties, we herein report the synthesis of mono- and di-glycosylated analogues of pramlintide and their activity at the AMY1(a) receptor. 27139251 1 1 theme diabetes 294:301 arg1 mellitus 303:310 diabetes mellitus 294:310 diabetes mellitus 294:310 Pramlintide (Symlin®), a synthetic analogue of the neuroendocrine hormone amylin, is devoid of the tendency to form cytotoxic amyloid fibrils and is currently used in patients with type I and type II diabetes mellitus as an adjunctive therapy with insulin or insulin analogues. 27139251 4 2 theme AMY1 850:853 arg1 activity 867:874 AMY1(a) receptor activity 850:874 AMY1(a) receptor activity 850:874 AMY1(a) receptor activity was retained by incorporation of single or multiple GlcNAc moieties at positions 21 and 35 of native pramlintide. 27139251 2 3 with analogue 420:427 arg1 properties 459:468 improved pharmacokinetic properties 434:468 improved pharmacokinetic properties 434:468 As part of an on-going search for a pramlintide analogue with improved pharmacokinetic properties, we herein report the synthesis of mono- and di-glycosylated analogues of pramlintide and their activity at the AMY1(a) receptor. 27139251 5 4 from N-glycosides 1203:1214 arg1 setting 1232:1238 a biological setting 1219:1238 a biological setting 1219:1238 Importantly, no difference in AMY1(a) activity was observed between native N-linked glycomimetics and 1,2,3-triazole linked glycomimetics demonstrating that the click variants can act as surrogates for the native N-glycosides in a biological setting. 27139251 4 5 theme receptor 858:865 arg1 activity 867:874 AMY1(a) receptor activity 850:874 AMY1(a) receptor activity 850:874 AMY1(a) receptor activity was retained by incorporation of single or multiple GlcNAc moieties at positions 21 and 35 of native pramlintide. 27139251 0 6 theme click 77:81 arg1 chemistry 83:91 click chemistry 77:91 click chemistry 77:91 Synthesis and amylin receptor activity of glycomimetics of pramlintide using click chemistry. 27139251 3 7 dep delivered 803:811 arg1 i 733:733 i 733:733 i 733:733 Introduction of N-glycosylated amino acids into the pramlintide sequence afforded the native N-linked glycomimetics whilst use of Cu(i)-catalysed azide-alkyne 1,3-dipolar cycloaddition (click) chemistry delivered 1,2,3-triazole linked glycomimetics. 27139251 1 8 theme neuroendocrine 145:158 arg1 amylin 168:173 the neuroendocrine hormone amylin 141:173 the neuroendocrine hormone amylin 141:173 Pramlintide (Symlin®), a synthetic analogue of the neuroendocrine hormone amylin, is devoid of the tendency to form cytotoxic amyloid fibrils and is currently used in patients with type I and type II diabetes mellitus as an adjunctive therapy with insulin or insulin analogues. 27139251 5 9 theme 1,2,3-triazole 1092:1105 arg1 glycomimetics 1114:1126 1,2,3-triazole linked glycomimetics 1092:1126 1,2,3-triazole linked glycomimetics 1092:1126 Importantly, no difference in AMY1(a) activity was observed between native N-linked glycomimetics and 1,2,3-triazole linked glycomimetics demonstrating that the click variants can act as surrogates for the native N-glycosides in a biological setting. 27139251 4 10 theme a 855:855 arg1 activity 867:874 AMY1(a) receptor activity 850:874 AMY1(a) receptor activity 850:874 AMY1(a) receptor activity was retained by incorporation of single or multiple GlcNAc moieties at positions 21 and 35 of native pramlintide. 27139251 5 11 theme click 1151:1155 arg1 surrogates 1177:1186 surrogates 1177:1186 surrogates for the native N-glycosides in a biological setting 1177:1238 Importantly, no difference in AMY1(a) activity was observed between native N-linked glycomimetics and 1,2,3-triazole linked glycomimetics demonstrating that the click variants can act as surrogates for the native N-glycosides in a biological setting. 27139251 5 11 theme click 1151:1155 arg1 variants 1157:1164 the click variants 1147:1164 the click variants 1147:1164 Importantly, no difference in AMY1(a) activity was observed between native N-linked glycomimetics and 1,2,3-triazole linked glycomimetics demonstrating that the click variants can act as surrogates for the native N-glycosides in a biological setting. 27139251 3 12 theme N-linked 693:700 arg1 glycomimetics 702:714 the native N-linked glycomimetics 682:714 the native N-linked glycomimetics 682:714 Introduction of N-glycosylated amino acids into the pramlintide sequence afforded the native N-linked glycomimetics whilst use of Cu(i)-catalysed azide-alkyne 1,3-dipolar cycloaddition (click) chemistry delivered 1,2,3-triazole linked glycomimetics. 27139251 4 13 theme single 909:914 arg1 moieties 935:942 single or multiple GlcNAc moieties 909:942 single or multiple GlcNAc moieties 909:942 AMY1(a) receptor activity was retained by incorporation of single or multiple GlcNAc moieties at positions 21 and 35 of native pramlintide. 27139251 3 14 theme native 686:691 arg1 glycomimetics 702:714 the native N-linked glycomimetics 682:714 the native N-linked glycomimetics 682:714 Introduction of N-glycosylated amino acids into the pramlintide sequence afforded the native N-linked glycomimetics whilst use of Cu(i)-catalysed azide-alkyne 1,3-dipolar cycloaddition (click) chemistry delivered 1,2,3-triazole linked glycomimetics. 27139251 3 15 theme click 786:790 arg1 chemistry 793:801 -catalysed azide-alkyne 1,3-dipolar cycloaddition (click) chemistry 735:801 -catalysed azide-alkyne 1,3-dipolar cycloaddition (click) chemistry 735:801 Introduction of N-glycosylated amino acids into the pramlintide sequence afforded the native N-linked glycomimetics whilst use of Cu(i)-catalysed azide-alkyne 1,3-dipolar cycloaddition (click) chemistry delivered 1,2,3-triazole linked glycomimetics. 27139251 4 16 theme GlcNAc 928:933 arg1 moieties 935:942 single or multiple GlcNAc moieties 909:942 single or multiple GlcNAc moieties 909:942 AMY1(a) receptor activity was retained by incorporation of single or multiple GlcNAc moieties at positions 21 and 35 of native pramlintide. 27139251 1 17 theme adjunctive 318:327 arg1 Pramlintide 94:104 Pramlintide 94:104 Pramlintide (Symlin®) 94:114 Pramlintide (Symlin®), a synthetic analogue of the neuroendocrine hormone amylin, is devoid of the tendency to form cytotoxic amyloid fibrils and is currently used in patients with type I and type II diabetes mellitus as an adjunctive therapy with insulin or insulin analogues. 27139251 1 17 theme adjunctive 318:327 arg1 therapy 329:335 an adjunctive therapy 315:335 an adjunctive therapy with insulin or insulin analogues 315:369 Pramlintide (Symlin®), a synthetic analogue of the neuroendocrine hormone amylin, is devoid of the tendency to form cytotoxic amyloid fibrils and is currently used in patients with type I and type II diabetes mellitus as an adjunctive therapy with insulin or insulin analogues. 27139251 2 18 theme a 587:587 arg1 receptor 590:597 the AMY1(a) receptor 578:597 the AMY1(a) receptor 578:597 As part of an on-going search for a pramlintide analogue with improved pharmacokinetic properties, we herein report the synthesis of mono- and di-glycosylated analogues of pramlintide and their activity at the AMY1(a) receptor. 27139251 5 19 theme biological 1221:1230 arg1 setting 1232:1238 a biological setting 1219:1238 a biological setting 1219:1238 Importantly, no difference in AMY1(a) activity was observed between native N-linked glycomimetics and 1,2,3-triazole linked glycomimetics demonstrating that the click variants can act as surrogates for the native N-glycosides in a biological setting. 27139251 1 20 theme hormone 160:166 arg1 amylin 168:173 the neuroendocrine hormone amylin 141:173 the neuroendocrine hormone amylin 141:173 Pramlintide (Symlin®), a synthetic analogue of the neuroendocrine hormone amylin, is devoid of the tendency to form cytotoxic amyloid fibrils and is currently used in patients with type I and type II diabetes mellitus as an adjunctive therapy with insulin or insulin analogues. 27139251 2 21 theme improved 434:441 arg1 properties 459:468 improved pharmacokinetic properties 434:468 improved pharmacokinetic properties 434:468 As part of an on-going search for a pramlintide analogue with improved pharmacokinetic properties, we herein report the synthesis of mono- and di-glycosylated analogues of pramlintide and their activity at the AMY1(a) receptor. 27139251 1 22 dep type 275:278 arg1 mellitus 303:310 diabetes mellitus 294:310 diabetes mellitus 294:310 Pramlintide (Symlin®), a synthetic analogue of the neuroendocrine hormone amylin, is devoid of the tendency to form cytotoxic amyloid fibrils and is currently used in patients with type I and type II diabetes mellitus as an adjunctive therapy with insulin or insulin analogues. 27139251 5 23 theme N-linked 1065:1072 arg1 glycomimetics 1074:1086 native N-linked glycomimetics 1058:1086 native N-linked glycomimetics 1058:1086 Importantly, no difference in AMY1(a) activity was observed between native N-linked glycomimetics and 1,2,3-triazole linked glycomimetics demonstrating that the click variants can act as surrogates for the native N-glycosides in a biological setting. 27139251 1 24 with patients 261:268 arg1 type 275:278 type I 275:280 type I 275:280 Pramlintide (Symlin®), a synthetic analogue of the neuroendocrine hormone amylin, is devoid of the tendency to form cytotoxic amyloid fibrils and is currently used in patients with type I and type II diabetes mellitus as an adjunctive therapy with insulin or insulin analogues. 27139251 1 24 with patients 261:268 arg1 type 286:289 type II 286:292 type II 286:292 Pramlintide (Symlin®), a synthetic analogue of the neuroendocrine hormone amylin, is devoid of the tendency to form cytotoxic amyloid fibrils and is currently used in patients with type I and type II diabetes mellitus as an adjunctive therapy with insulin or insulin analogues. 27139251 4 25 theme pramlintide 977:987 arg1 positions 947:955 positions 21 and 35 947:965 positions 947:955 AMY1(a) receptor activity was retained by incorporation of single or multiple GlcNAc moieties at positions 21 and 35 of native pramlintide. 27139251 1 26 theme amylin 168:173 arg1 Pramlintide 94:104 Pramlintide 94:104 Pramlintide (Symlin®) 94:114 Pramlintide (Symlin®), a synthetic analogue of the neuroendocrine hormone amylin, is devoid of the tendency to form cytotoxic amyloid fibrils and is currently used in patients with type I and type II diabetes mellitus as an adjunctive therapy with insulin or insulin analogues. 27139251 1 26 theme amylin 168:173 arg1 analogue 129:136 a synthetic analogue 117:136 a synthetic analogue of the neuroendocrine hormone amylin 117:173 Pramlintide (Symlin®), a synthetic analogue of the neuroendocrine hormone amylin, is devoid of the tendency to form cytotoxic amyloid fibrils and is currently used in patients with type I and type II diabetes mellitus as an adjunctive therapy with insulin or insulin analogues. 27139251 1 27 used used 253:256 arg2 Symlin® 107:113 Symlin® 107:113 Symlin® 107:113 Pramlintide (Symlin®), a synthetic analogue of the neuroendocrine hormone amylin, is devoid of the tendency to form cytotoxic amyloid fibrils and is currently used in patients with type I and type II diabetes mellitus as an adjunctive therapy with insulin or insulin analogues. 27139251 1 27 used used 253:256 arg2 Pramlintide 94:104 Pramlintide 94:104 Pramlintide (Symlin®) 94:114 Pramlintide (Symlin®), a synthetic analogue of the neuroendocrine hormone amylin, is devoid of the tendency to form cytotoxic amyloid fibrils and is currently used in patients with type I and type II diabetes mellitus as an adjunctive therapy with insulin or insulin analogues. 27139251 1 27 used used 253:256 arg2 therapy 329:335 an adjunctive therapy 315:335 an adjunctive therapy with insulin or insulin analogues 315:369 Pramlintide (Symlin®), a synthetic analogue of the neuroendocrine hormone amylin, is devoid of the tendency to form cytotoxic amyloid fibrils and is currently used in patients with type I and type II diabetes mellitus as an adjunctive therapy with insulin or insulin analogues. 27139251 1 27 used used 253:256 arg2 analogue 129:136 a synthetic analogue 117:136 a synthetic analogue of the neuroendocrine hormone amylin 117:173 Pramlintide (Symlin®), a synthetic analogue of the neuroendocrine hormone amylin, is devoid of the tendency to form cytotoxic amyloid fibrils and is currently used in patients with type I and type II diabetes mellitus as an adjunctive therapy with insulin or insulin analogues. 27139251 2 28 theme AMY1 582:585 arg1 receptor 590:597 the AMY1(a) receptor 578:597 the AMY1(a) receptor 578:597 As part of an on-going search for a pramlintide analogue with improved pharmacokinetic properties, we herein report the synthesis of mono- and di-glycosylated analogues of pramlintide and their activity at the AMY1(a) receptor. 27139251 3 29 link N-linked 693:700 arg1 glycomimetics 702:714 the native N-linked glycomimetics 682:714 the native N-linked glycomimetics 682:714 Introduction of N-glycosylated amino acids into the pramlintide sequence afforded the native N-linked glycomimetics whilst use of Cu(i)-catalysed azide-alkyne 1,3-dipolar cycloaddition (click) chemistry delivered 1,2,3-triazole linked glycomimetics. 27139251 2 30 theme search 395:400 arg1 part 375:378 part 375:378 part of an on-going search for a pramlintide analogue with improved pharmacokinetic properties 375:468 As part of an on-going search for a pramlintide analogue with improved pharmacokinetic properties, we herein report the synthesis of mono- and di-glycosylated analogues of pramlintide and their activity at the AMY1(a) receptor. 27139251 5 31 theme AMY1 1020:1023 arg1 activity 1028:1035 AMY1(a) activity 1020:1035 AMY1(a) activity 1020:1035 Importantly, no difference in AMY1(a) activity was observed between native N-linked glycomimetics and 1,2,3-triazole linked glycomimetics demonstrating that the click variants can act as surrogates for the native N-glycosides in a biological setting. 27139251 4 32 theme native 970:975 arg1 pramlintide 977:987 native pramlintide 970:987 native pramlintide 970:987 AMY1(a) receptor activity was retained by incorporation of single or multiple GlcNAc moieties at positions 21 and 35 of native pramlintide. 27139251 0 33 theme receptor 21:28 arg1 activity 30:37 amylin receptor activity 14:37 amylin receptor activity 14:37 Synthesis and amylin receptor activity of glycomimetics of pramlintide using click chemistry. 27139251 3 34 theme -catalysed 735:744 arg1 chemistry 793:801 -catalysed azide-alkyne 1,3-dipolar cycloaddition (click) chemistry 735:801 -catalysed azide-alkyne 1,3-dipolar cycloaddition (click) chemistry 735:801 Introduction of N-glycosylated amino acids into the pramlintide sequence afforded the native N-linked glycomimetics whilst use of Cu(i)-catalysed azide-alkyne 1,3-dipolar cycloaddition (click) chemistry delivered 1,2,3-triazole linked glycomimetics. 27139251 4 35 from 35 964:965 arg1 incorporation 892:904 incorporation 892:904 incorporation of single or multiple GlcNAc moieties at positions 21 and 35 of native pramlintide 892:987 AMY1(a) receptor activity was retained by incorporation of single or multiple GlcNAc moieties at positions 21 and 35 of native pramlintide. 27139251 5 36 from difference 1006:1015 arg1 activity 1028:1035 AMY1(a) activity 1020:1035 AMY1(a) activity 1020:1035 Importantly, no difference in AMY1(a) activity was observed between native N-linked glycomimetics and 1,2,3-triazole linked glycomimetics demonstrating that the click variants can act as surrogates for the native N-glycosides in a biological setting. 27139251 5 37 theme native 1196:1201 arg1 N-glycosides 1203:1214 the native N-glycosides 1192:1214 the native N-glycosides in a biological setting 1192:1238 Importantly, no difference in AMY1(a) activity was observed between native N-linked glycomimetics and 1,2,3-triazole linked glycomimetics demonstrating that the click variants can act as surrogates for the native N-glycosides in a biological setting. 27139251 0 38 theme amylin 14:19 arg1 activity 30:37 amylin receptor activity 14:37 amylin receptor activity 14:37 Synthesis and amylin receptor activity of glycomimetics of pramlintide using click chemistry. 27139251 2 39 theme mono- 505:509 arg1 analogues 531:539 mono- and di-glycosylated analogues 505:539 mono- and di-glycosylated analogues of pramlintide 505:554 As part of an on-going search for a pramlintide analogue with improved pharmacokinetic properties, we herein report the synthesis of mono- and di-glycosylated analogues of pramlintide and their activity at the AMY1(a) receptor. 27139251 5 40 link N-linked 1065:1072 arg1 glycomimetics 1074:1086 native N-linked glycomimetics 1058:1086 native N-linked glycomimetics 1058:1086 Importantly, no difference in AMY1(a) activity was observed between native N-linked glycomimetics and 1,2,3-triazole linked glycomimetics demonstrating that the click variants can act as surrogates for the native N-glycosides in a biological setting. 27139251 3 41 gly N-glycosylated 616:629 arg1 acids 637:641 N-glycosylated amino acids 616:641 N-glycosylated amino acids 616:641 Introduction of N-glycosylated amino acids into the pramlintide sequence afforded the native N-linked glycomimetics whilst use of Cu(i)-catalysed azide-alkyne 1,3-dipolar cycloaddition (click) chemistry delivered 1,2,3-triazole linked glycomimetics. 27139251 3 42 theme linked 828:833 arg1 glycomimetics 835:847 1,2,3-triazole linked glycomimetics 813:847 1,2,3-triazole linked glycomimetics 813:847 Introduction of N-glycosylated amino acids into the pramlintide sequence afforded the native N-linked glycomimetics whilst use of Cu(i)-catalysed azide-alkyne 1,3-dipolar cycloaddition (click) chemistry delivered 1,2,3-triazole linked glycomimetics. 27139251 3 43 dep afforded 673:680 arg1 delivered 803:811 delivered 803:811 delivered 1,2,3-triazole linked glycomimetics 803:847 Introduction of N-glycosylated amino acids into the pramlintide sequence afforded the native N-linked glycomimetics whilst use of Cu(i)-catalysed azide-alkyne 1,3-dipolar cycloaddition (click) chemistry delivered 1,2,3-triazole linked glycomimetics. 27139251 1 44 theme insulin 353:359 arg1 analogues 361:369 insulin analogues 353:369 insulin analogues 353:369 Pramlintide (Symlin®), a synthetic analogue of the neuroendocrine hormone amylin, is devoid of the tendency to form cytotoxic amyloid fibrils and is currently used in patients with type I and type II diabetes mellitus as an adjunctive therapy with insulin or insulin analogues. 27139251 2 45 theme on-going 386:393 arg1 search 395:400 an on-going search 383:400 an on-going search for a pramlintide analogue with improved pharmacokinetic properties 383:468 As part of an on-going search for a pramlintide analogue with improved pharmacokinetic properties, we herein report the synthesis of mono- and di-glycosylated analogues of pramlintide and their activity at the AMY1(a) receptor. 27139251 1 46 theme tendency 193:200 arg1 devoid 179:184 devoid 179:184 devoid 179:184 Pramlintide (Symlin®), a synthetic analogue of the neuroendocrine hormone amylin, is devoid of the tendency to form cytotoxic amyloid fibrils and is currently used in patients with type I and type II diabetes mellitus as an adjunctive therapy with insulin or insulin analogues. 27139251 2 47 theme pramlintide 408:418 arg1 analogue 420:427 a pramlintide analogue 406:427 a pramlintide analogue with improved pharmacokinetic properties 406:468 As part of an on-going search for a pramlintide analogue with improved pharmacokinetic properties, we herein report the synthesis of mono- and di-glycosylated analogues of pramlintide and their activity at the AMY1(a) receptor. 27139251 5 48 theme linked 1107:1112 arg1 glycomimetics 1114:1126 1,2,3-triazole linked glycomimetics 1092:1126 1,2,3-triazole linked glycomimetics 1092:1126 Importantly, no difference in AMY1(a) activity was observed between native N-linked glycomimetics and 1,2,3-triazole linked glycomimetics demonstrating that the click variants can act as surrogates for the native N-glycosides in a biological setting. 27139251 2 49 theme pramlintide 544:554 arg1 analogues 531:539 mono- and di-glycosylated analogues 505:539 mono- and di-glycosylated analogues of pramlintide 505:554 As part of an on-going search for a pramlintide analogue with improved pharmacokinetic properties, we herein report the synthesis of mono- and di-glycosylated analogues of pramlintide and their activity at the AMY1(a) receptor. 27139251 4 50 theme moieties 935:942 arg1 incorporation 892:904 incorporation 892:904 incorporation of single or multiple GlcNAc moieties at positions 21 and 35 of native pramlintide 892:987 AMY1(a) receptor activity was retained by incorporation of single or multiple GlcNAc moieties at positions 21 and 35 of native pramlintide. 27139251 2 51 from receptor 590:597 arg1 activity 566:573 their activity 560:573 their activity at the AMY1(a) receptor 560:597 As part of an on-going search for a pramlintide analogue with improved pharmacokinetic properties, we herein report the synthesis of mono- and di-glycosylated analogues of pramlintide and their activity at the AMY1(a) receptor. 27139251 2 51 from receptor 590:597 arg1 synthesis 492:500 the synthesis 488:500 the synthesis of mono- and di-glycosylated analogues of pramlintide 488:554 As part of an on-going search for a pramlintide analogue with improved pharmacokinetic properties, we herein report the synthesis of mono- and di-glycosylated analogues of pramlintide and their activity at the AMY1(a) receptor. 27139251 0 52 theme glycomimetics 42:54 arg1 Synthesis 0:8 Synthesis 0:8 Synthesis 0:8 Synthesis and amylin receptor activity of glycomimetics of pramlintide using click chemistry. 27139251 0 52 theme glycomimetics 42:54 arg1 activity 30:37 amylin receptor activity 14:37 amylin receptor activity 14:37 Synthesis and amylin receptor activity of glycomimetics of pramlintide using click chemistry. 27139251 3 53 theme Cu 730:731 arg1 use 723:725 use 723:725 use of Cu 723:731 Introduction of N-glycosylated amino acids into the pramlintide sequence afforded the native N-linked glycomimetics whilst use of Cu(i)-catalysed azide-alkyne 1,3-dipolar cycloaddition (click) chemistry delivered 1,2,3-triazole linked glycomimetics. 27139251 5 54 theme native 1058:1063 arg1 glycomimetics 1074:1086 native N-linked glycomimetics 1058:1086 native N-linked glycomimetics 1058:1086 Importantly, no difference in AMY1(a) activity was observed between native N-linked glycomimetics and 1,2,3-triazole linked glycomimetics demonstrating that the click variants can act as surrogates for the native N-glycosides in a biological setting. 27139251 3 55 theme amino 631:635 arg1 acids 637:641 N-glycosylated amino acids 616:641 N-glycosylated amino acids 616:641 Introduction of N-glycosylated amino acids into the pramlintide sequence afforded the native N-linked glycomimetics whilst use of Cu(i)-catalysed azide-alkyne 1,3-dipolar cycloaddition (click) chemistry delivered 1,2,3-triazole linked glycomimetics. 27139251 5 56 link linked 1107:1112 arg1 glycomimetics 1114:1126 1,2,3-triazole linked glycomimetics 1092:1126 1,2,3-triazole linked glycomimetics 1092:1126 Importantly, no difference in AMY1(a) activity was observed between native N-linked glycomimetics and 1,2,3-triazole linked glycomimetics demonstrating that the click variants can act as surrogates for the native N-glycosides in a biological setting. 27139251 1 57 with therapy 329:335 arg1 insulin 342:348 insulin 342:348 insulin 342:348 Pramlintide (Symlin®), a synthetic analogue of the neuroendocrine hormone amylin, is devoid of the tendency to form cytotoxic amyloid fibrils and is currently used in patients with type I and type II diabetes mellitus as an adjunctive therapy with insulin or insulin analogues. 27139251 1 57 with therapy 329:335 arg1 analogues 361:369 insulin analogues 353:369 insulin analogues 353:369 Pramlintide (Symlin®), a synthetic analogue of the neuroendocrine hormone amylin, is devoid of the tendency to form cytotoxic amyloid fibrils and is currently used in patients with type I and type II diabetes mellitus as an adjunctive therapy with insulin or insulin analogues. 27139251 4 58 from positions 947:955 arg1 incorporation 892:904 incorporation 892:904 incorporation of single or multiple GlcNAc moieties at positions 21 and 35 of native pramlintide 892:987 AMY1(a) receptor activity was retained by incorporation of single or multiple GlcNAc moieties at positions 21 and 35 of native pramlintide. 27139251 2 59 theme analogues 531:539 arg1 activity 566:573 their activity 560:573 their activity at the AMY1(a) receptor 560:597 As part of an on-going search for a pramlintide analogue with improved pharmacokinetic properties, we herein report the synthesis of mono- and di-glycosylated analogues of pramlintide and their activity at the AMY1(a) receptor. 27139251 2 59 theme analogues 531:539 arg1 synthesis 492:500 the synthesis 488:500 the synthesis of mono- and di-glycosylated analogues of pramlintide 488:554 As part of an on-going search for a pramlintide analogue with improved pharmacokinetic properties, we herein report the synthesis of mono- and di-glycosylated analogues of pramlintide and their activity at the AMY1(a) receptor. 27139251 3 60 theme acids 637:641 arg1 Introduction 600:611 Introduction 600:611 Introduction of N-glycosylated amino acids into the pramlintide sequence 600:671 Introduction of N-glycosylated amino acids into the pramlintide sequence afforded the native N-linked glycomimetics whilst use of Cu(i)-catalysed azide-alkyne 1,3-dipolar cycloaddition (click) chemistry delivered 1,2,3-triazole linked glycomimetics. 27139251 2 61 gly di-glycosylated 515:529 arg1 analogues 531:539 mono- and di-glycosylated analogues 505:539 mono- and di-glycosylated analogues of pramlintide 505:554 As part of an on-going search for a pramlintide analogue with improved pharmacokinetic properties, we herein report the synthesis of mono- and di-glycosylated analogues of pramlintide and their activity at the AMY1(a) receptor. 27139251 3 62 theme 1,3-dipolar 759:769 arg1 chemistry 793:801 -catalysed azide-alkyne 1,3-dipolar cycloaddition (click) chemistry 735:801 -catalysed azide-alkyne 1,3-dipolar cycloaddition (click) chemistry 735:801 Introduction of N-glycosylated amino acids into the pramlintide sequence afforded the native N-linked glycomimetics whilst use of Cu(i)-catalysed azide-alkyne 1,3-dipolar cycloaddition (click) chemistry delivered 1,2,3-triazole linked glycomimetics. 27139251 2 63 theme di-glycosylated 515:529 arg1 analogues 531:539 mono- and di-glycosylated analogues 505:539 mono- and di-glycosylated analogues of pramlintide 505:554 As part of an on-going search for a pramlintide analogue with improved pharmacokinetic properties, we herein report the synthesis of mono- and di-glycosylated analogues of pramlintide and their activity at the AMY1(a) receptor. 27139251 3 64 link linked 828:833 arg1 glycomimetics 835:847 1,2,3-triazole linked glycomimetics 813:847 1,2,3-triazole linked glycomimetics 813:847 Introduction of N-glycosylated amino acids into the pramlintide sequence afforded the native N-linked glycomimetics whilst use of Cu(i)-catalysed azide-alkyne 1,3-dipolar cycloaddition (click) chemistry delivered 1,2,3-triazole linked glycomimetics. 27139251 1 65 theme synthetic 119:127 arg1 Pramlintide 94:104 Pramlintide 94:104 Pramlintide (Symlin®) 94:114 Pramlintide (Symlin®), a synthetic analogue of the neuroendocrine hormone amylin, is devoid of the tendency to form cytotoxic amyloid fibrils and is currently used in patients with type I and type II diabetes mellitus as an adjunctive therapy with insulin or insulin analogues. 27139251 1 65 theme synthetic 119:127 arg1 analogue 129:136 a synthetic analogue 117:136 a synthetic analogue of the neuroendocrine hormone amylin 117:173 Pramlintide (Symlin®), a synthetic analogue of the neuroendocrine hormone amylin, is devoid of the tendency to form cytotoxic amyloid fibrils and is currently used in patients with type I and type II diabetes mellitus as an adjunctive therapy with insulin or insulin analogues. 27139251 3 66 theme cycloaddition 771:783 arg1 chemistry 793:801 -catalysed azide-alkyne 1,3-dipolar cycloaddition (click) chemistry 735:801 -catalysed azide-alkyne 1,3-dipolar cycloaddition (click) chemistry 735:801 Introduction of N-glycosylated amino acids into the pramlintide sequence afforded the native N-linked glycomimetics whilst use of Cu(i)-catalysed azide-alkyne 1,3-dipolar cycloaddition (click) chemistry delivered 1,2,3-triazole linked glycomimetics. 27139251 3 67 theme N-glycosylated 616:629 arg1 acids 637:641 N-glycosylated amino acids 616:641 N-glycosylated amino acids 616:641 Introduction of N-glycosylated amino acids into the pramlintide sequence afforded the native N-linked glycomimetics whilst use of Cu(i)-catalysed azide-alkyne 1,3-dipolar cycloaddition (click) chemistry delivered 1,2,3-triazole linked glycomimetics. 27139251 3 68 theme 1,2,3-triazole 813:826 arg1 glycomimetics 835:847 1,2,3-triazole linked glycomimetics 813:847 1,2,3-triazole linked glycomimetics 813:847 Introduction of N-glycosylated amino acids into the pramlintide sequence afforded the native N-linked glycomimetics whilst use of Cu(i)-catalysed azide-alkyne 1,3-dipolar cycloaddition (click) chemistry delivered 1,2,3-triazole linked glycomimetics. 27139251 1 69 theme cytotoxic 210:218 arg1 fibrils 228:234 cytotoxic amyloid fibrils 210:234 cytotoxic amyloid fibrils 210:234 Pramlintide (Symlin®), a synthetic analogue of the neuroendocrine hormone amylin, is devoid of the tendency to form cytotoxic amyloid fibrils and is currently used in patients with type I and type II diabetes mellitus as an adjunctive therapy with insulin or insulin analogues. 27139251 0 70 theme pramlintide 59:69 arg1 glycomimetics 42:54 glycomimetics 42:54 glycomimetics of pramlintide using click chemistry 42:91 Synthesis and amylin receptor activity of glycomimetics of pramlintide using click chemistry. 27139251 3 71 theme pramlintide 652:662 arg1 sequence 664:671 the pramlintide sequence 648:671 the pramlintide sequence 648:671 Introduction of N-glycosylated amino acids into the pramlintide sequence afforded the native N-linked glycomimetics whilst use of Cu(i)-catalysed azide-alkyne 1,3-dipolar cycloaddition (click) chemistry delivered 1,2,3-triazole linked glycomimetics. 27139251 3 72 theme azide-alkyne 746:757 arg1 chemistry 793:801 -catalysed azide-alkyne 1,3-dipolar cycloaddition (click) chemistry 735:801 -catalysed azide-alkyne 1,3-dipolar cycloaddition (click) chemistry 735:801 Introduction of N-glycosylated amino acids into the pramlintide sequence afforded the native N-linked glycomimetics whilst use of Cu(i)-catalysed azide-alkyne 1,3-dipolar cycloaddition (click) chemistry delivered 1,2,3-triazole linked glycomimetics. 27139251 4 73 theme multiple 919:926 arg1 moieties 935:942 single or multiple GlcNAc moieties 909:942 single or multiple GlcNAc moieties 909:942 AMY1(a) receptor activity was retained by incorporation of single or multiple GlcNAc moieties at positions 21 and 35 of native pramlintide. 27139251 1 74 theme amyloid 220:226 arg1 fibrils 228:234 cytotoxic amyloid fibrils 210:234 cytotoxic amyloid fibrils 210:234 Pramlintide (Symlin®), a synthetic analogue of the neuroendocrine hormone amylin, is devoid of the tendency to form cytotoxic amyloid fibrils and is currently used in patients with type I and type II diabetes mellitus as an adjunctive therapy with insulin or insulin analogues. 25139987 0 0 theme Bacteroides 79:89 arg1 fragilis 91:98 Bacteroides fragilis 79:98 Bacteroides fragilis in extraintestinal infections 79:128 Efficient utilization of complex N-linked glycans is a selective advantage for Bacteroides fragilis in extraintestinal infections. 25139987 5 1 theme glycoprotein 634:645 arg1 transferrin 647:657 the abundant serum glycoprotein transferrin 615:657 the abundant serum glycoprotein transferrin 615:657 Using the abundant serum glycoprotein transferrin as a model, it has been shown that B. fragilis alone can rapidly and efficiently deglycosylate this protein in vitro and that transferrin glycans can provide the sole source of carbon and energy for growth in defined media. 25139987 5 1 theme glycoprotein 634:645 arg1 model 664:668 a model 662:668 a model 662:668 Using the abundant serum glycoprotein transferrin as a model, it has been shown that B. fragilis alone can rapidly and efficiently deglycosylate this protein in vitro and that transferrin glycans can provide the sole source of carbon and energy for growth in defined media. 25139987 1 2 theme common 164:169 arg1 fragilis 143:150 Bacteroides fragilis 131:150 Bacteroides fragilis 131:150 Bacteroides fragilis is the most common anaerobe isolated from clinical infections, and in this report we demonstrate a characteristic of the species that is critical to their success as an opportunistic pathogen. 25139987 1 2 theme common 164:169 arg1 anaerobe 171:178 the most common anaerobe 155:178 the most common anaerobe isolated from clinical infections 155:212 Bacteroides fragilis is the most common anaerobe isolated from clinical infections, and in this report we demonstrate a characteristic of the species that is critical to their success as an opportunistic pathogen. 25139987 4 3 theme membrane 565:572 arg1 complex 582:588 an outer membrane protein complex 556:588 an outer membrane protein complex designated as Don 556:606 This activity is mediated by an outer membrane protein complex designated as Don. 25139987 6 4 theme extraintestinal 1009:1023 arg1 growth 1025:1030 extraintestinal growth 1009:1030 extraintestinal growth 1009:1030 We then showed that transferrin deglycosylation occurs in vivo when B. fragilis is propagated in the rat tissue cage model of extraintestinal growth, and that this ability provides a competitive advantage in vivo over strains lacking the don locus. 25139987 5 5 theme defined 868:874 arg1 media 876:880 defined media 868:880 defined media 868:880 Using the abundant serum glycoprotein transferrin as a model, it has been shown that B. fragilis alone can rapidly and efficiently deglycosylate this protein in vitro and that transferrin glycans can provide the sole source of carbon and energy for growth in defined media. 25139987 4 6 theme outer 559:563 arg1 complex 582:588 an outer membrane protein complex 556:588 an outer membrane protein complex designated as Don 556:606 This activity is mediated by an outer membrane protein complex designated as Don. 25139987 3 7 link N-linked 453:460 arg1 glycans 462:468 efficiently harvesting complex N-linked glycans 422:468 efficiently harvesting complex N-linked glycans from the glycoproteins common to serum and serous fluid 422:524 in the gut, B. fragilis has the unique ability of efficiently harvesting complex N-linked glycans from the glycoproteins common to serum and serous fluid. 25139987 2 8 theme Bacteroides 355:365 arg1 spp 367:369 the Bacteroides spp 351:369 the Bacteroides spp 351:369 Among the Bacteroides spp. 25139987 1 9 theme species 273:279 arg1 critical 289:296 critical 289:296 critical 289:296 Bacteroides fragilis is the most common anaerobe isolated from clinical infections, and in this report we demonstrate a characteristic of the species that is critical to their success as an opportunistic pathogen. 25139987 1 9 theme species 273:279 arg1 characteristic 251:264 a characteristic 249:264 a characteristic of the species that is critical to their success as an opportunistic pathogen 249:342 Bacteroides fragilis is the most common anaerobe isolated from clinical infections, and in this report we demonstrate a characteristic of the species that is critical to their success as an opportunistic pathogen. 25139987 5 10 theme sole 821:824 arg1 source 826:831 the sole source 817:831 the sole source of carbon and energy for growth in defined media 817:880 Using the abundant serum glycoprotein transferrin as a model, it has been shown that B. fragilis alone can rapidly and efficiently deglycosylate this protein in vitro and that transferrin glycans can provide the sole source of carbon and energy for growth in defined media. 25139987 3 11 contain has 396:398 arg1 fragilis 387:394 B. fragilis 384:394 B. fragilis 384:394 in the gut, B. fragilis has the unique ability of efficiently harvesting complex N-linked glycans from the glycoproteins common to serum and serous fluid. 25139987 3 11 contain has 396:398 arg2 ability 411:417 the unique ability 400:417 the unique ability of efficiently harvesting complex N-linked glycans from the glycoproteins common to serum and serous fluid 400:524 in the gut, B. fragilis has the unique ability of efficiently harvesting complex N-linked glycans from the glycoproteins common to serum and serous fluid. 25139987 1 12 theme clinical 194:201 arg1 infections 203:212 clinical infections 194:212 clinical infections 194:212 Bacteroides fragilis is the most common anaerobe isolated from clinical infections, and in this report we demonstrate a characteristic of the species that is critical to their success as an opportunistic pathogen. 25139987 0 13 theme extraintestinal 103:117 arg1 infections 119:128 extraintestinal infections 103:128 extraintestinal infections 103:128 Efficient utilization of complex N-linked glycans is a selective advantage for Bacteroides fragilis in extraintestinal infections. 25139987 5 14 gly deglycosylate 740:752 arg1 protein 759:765 this protein 754:765 this protein 754:765 Using the abundant serum glycoprotein transferrin as a model, it has been shown that B. fragilis alone can rapidly and efficiently deglycosylate this protein in vitro and that transferrin glycans can provide the sole source of carbon and energy for growth in defined media. 25139987 5 15 gly glycoprotein 634:645 arg1 glycoprotein 634:645 the abundant serum glycoprotein transferrin 615:657 the abundant serum glycoprotein transferrin 615:657 Using the abundant serum glycoprotein transferrin as a model, it has been shown that B. fragilis alone can rapidly and efficiently deglycosylate this protein in vitro and that transferrin glycans can provide the sole source of carbon and energy for growth in defined media. 25139987 5 16 theme abundant 619:626 arg1 transferrin 647:657 the abundant serum glycoprotein transferrin 615:657 the abundant serum glycoprotein transferrin 615:657 Using the abundant serum glycoprotein transferrin as a model, it has been shown that B. fragilis alone can rapidly and efficiently deglycosylate this protein in vitro and that transferrin glycans can provide the sole source of carbon and energy for growth in defined media. 25139987 5 16 theme abundant 619:626 arg1 model 664:668 a model 662:668 a model 662:668 Using the abundant serum glycoprotein transferrin as a model, it has been shown that B. fragilis alone can rapidly and efficiently deglycosylate this protein in vitro and that transferrin glycans can provide the sole source of carbon and energy for growth in defined media. 25139987 3 17 theme unique 404:409 arg1 ability 411:417 the unique ability 400:417 the unique ability of efficiently harvesting complex N-linked glycans from the glycoproteins common to serum and serous fluid 400:524 in the gut, B. fragilis has the unique ability of efficiently harvesting complex N-linked glycans from the glycoproteins common to serum and serous fluid. 25139987 0 18 theme Efficient 0:8 arg1 utilization 10:20 Efficient utilization 0:20 Efficient utilization of complex N-linked glycans 0:48 Efficient utilization of complex N-linked glycans is a selective advantage for Bacteroides fragilis in extraintestinal infections. 25139987 0 18 theme Efficient 0:8 arg1 advantage 65:73 a selective advantage 53:73 a selective advantage for Bacteroides fragilis in extraintestinal infections 53:128 Efficient utilization of complex N-linked glycans is a selective advantage for Bacteroides fragilis in extraintestinal infections. 25139987 5 19 theme serum 628:632 arg1 transferrin 647:657 the abundant serum glycoprotein transferrin 615:657 the abundant serum glycoprotein transferrin 615:657 Using the abundant serum glycoprotein transferrin as a model, it has been shown that B. fragilis alone can rapidly and efficiently deglycosylate this protein in vitro and that transferrin glycans can provide the sole source of carbon and energy for growth in defined media. 25139987 5 19 theme serum 628:632 arg1 model 664:668 a model 662:668 a model 662:668 Using the abundant serum glycoprotein transferrin as a model, it has been shown that B. fragilis alone can rapidly and efficiently deglycosylate this protein in vitro and that transferrin glycans can provide the sole source of carbon and energy for growth in defined media. 25139987 3 20 from glycoproteins 479:491 arg1 ability 411:417 the unique ability 400:417 the unique ability of efficiently harvesting complex N-linked glycans from the glycoproteins common to serum and serous fluid 400:524 in the gut, B. fragilis has the unique ability of efficiently harvesting complex N-linked glycans from the glycoproteins common to serum and serous fluid. 25139987 3 20 from glycoproteins 479:491 arg1 glycans 462:468 efficiently harvesting complex N-linked glycans 422:468 efficiently harvesting complex N-linked glycans from the glycoproteins common to serum and serous fluid 422:524 in the gut, B. fragilis has the unique ability of efficiently harvesting complex N-linked glycans from the glycoproteins common to serum and serous fluid. 25139987 3 21 gly glycoproteins 479:491 arg1 glycoproteins 479:491 the glycoproteins 475:491 the glycoproteins common to serum and serous fluid 475:524 in the gut, B. fragilis has the unique ability of efficiently harvesting complex N-linked glycans from the glycoproteins common to serum and serous fluid. 25139987 5 22 theme energy 847:852 arg1 source 826:831 the sole source 817:831 the sole source of carbon and energy for growth in defined media 817:880 Using the abundant serum glycoprotein transferrin as a model, it has been shown that B. fragilis alone can rapidly and efficiently deglycosylate this protein in vitro and that transferrin glycans can provide the sole source of carbon and energy for growth in defined media. 25139987 0 23 theme complex 25:31 arg1 glycans 42:48 complex N-linked glycans 25:48 complex N-linked glycans 25:48 Efficient utilization of complex N-linked glycans is a selective advantage for Bacteroides fragilis in extraintestinal infections. 25139987 5 24 theme transferrin 785:795 arg1 glycans 797:803 transferrin glycans 785:803 transferrin glycans 785:803 Using the abundant serum glycoprotein transferrin as a model, it has been shown that B. fragilis alone can rapidly and efficiently deglycosylate this protein in vitro and that transferrin glycans can provide the sole source of carbon and energy for growth in defined media. 25139987 0 25 link N-linked 33:40 arg1 glycans 42:48 complex N-linked glycans 25:48 complex N-linked glycans 25:48 Efficient utilization of complex N-linked glycans is a selective advantage for Bacteroides fragilis in extraintestinal infections. 25139987 3 26 theme N-linked 453:460 arg1 glycans 462:468 efficiently harvesting complex N-linked glycans 422:468 efficiently harvesting complex N-linked glycans from the glycoproteins common to serum and serous fluid 422:524 in the gut, B. fragilis has the unique ability of efficiently harvesting complex N-linked glycans from the glycoproteins common to serum and serous fluid. 25139987 3 27 theme glycans 462:468 arg1 ability 411:417 the unique ability 400:417 the unique ability of efficiently harvesting complex N-linked glycans from the glycoproteins common to serum and serous fluid 400:524 in the gut, B. fragilis has the unique ability of efficiently harvesting complex N-linked glycans from the glycoproteins common to serum and serous fluid. 25139987 0 28 theme glycans 42:48 arg1 utilization 10:20 Efficient utilization 0:20 Efficient utilization of complex N-linked glycans 0:48 Efficient utilization of complex N-linked glycans is a selective advantage for Bacteroides fragilis in extraintestinal infections. 25139987 0 28 theme glycans 42:48 arg1 advantage 65:73 a selective advantage 53:73 a selective advantage for Bacteroides fragilis in extraintestinal infections 53:128 Efficient utilization of complex N-linked glycans is a selective advantage for Bacteroides fragilis in extraintestinal infections. 25139987 3 29 theme common 493:498 arg1 glycoproteins 479:491 the glycoproteins 475:491 the glycoproteins common to serum and serous fluid 475:524 in the gut, B. fragilis has the unique ability of efficiently harvesting complex N-linked glycans from the glycoproteins common to serum and serous fluid. 25139987 1 30 attach isolated 180:187 arg2 anaerobe 171:178 the most common anaerobe 155:178 the most common anaerobe isolated from clinical infections 155:212 Bacteroides fragilis is the most common anaerobe isolated from clinical infections, and in this report we demonstrate a characteristic of the species that is critical to their success as an opportunistic pathogen. 25139987 1 30 attach isolated 180:187 arg1 infections 203:212 clinical infections 194:212 clinical infections 194:212 Bacteroides fragilis is the most common anaerobe isolated from clinical infections, and in this report we demonstrate a characteristic of the species that is critical to their success as an opportunistic pathogen. 25139987 1 30 attach isolated 180:187 arg2 fragilis 143:150 Bacteroides fragilis 131:150 Bacteroides fragilis 131:150 Bacteroides fragilis is the most common anaerobe isolated from clinical infections, and in this report we demonstrate a characteristic of the species that is critical to their success as an opportunistic pathogen. 25139987 6 31 theme growth 1025:1030 arg1 model 1000:1004 the rat tissue cage model 980:1004 the rat tissue cage model of extraintestinal growth 980:1030 We then showed that transferrin deglycosylation occurs in vivo when B. fragilis is propagated in the rat tissue cage model of extraintestinal growth, and that this ability provides a competitive advantage in vivo over strains lacking the don locus. 25139987 3 32 theme harvesting 434:443 arg1 glycans 462:468 efficiently harvesting complex N-linked glycans 422:468 efficiently harvesting complex N-linked glycans from the glycoproteins common to serum and serous fluid 422:524 in the gut, B. fragilis has the unique ability of efficiently harvesting complex N-linked glycans from the glycoproteins common to serum and serous fluid. 25139987 0 33 theme N-linked 33:40 arg1 glycans 42:48 complex N-linked glycans 25:48 complex N-linked glycans 25:48 Efficient utilization of complex N-linked glycans is a selective advantage for Bacteroides fragilis in extraintestinal infections. 25139987 3 34 theme complex 445:451 arg1 glycans 462:468 efficiently harvesting complex N-linked glycans 422:468 efficiently harvesting complex N-linked glycans from the glycoproteins common to serum and serous fluid 422:524 in the gut, B. fragilis has the unique ability of efficiently harvesting complex N-linked glycans from the glycoproteins common to serum and serous fluid. 25139987 5 35 from growth 858:863 arg1 media 876:880 defined media 868:880 defined media 868:880 Using the abundant serum glycoprotein transferrin as a model, it has been shown that B. fragilis alone can rapidly and efficiently deglycosylate this protein in vitro and that transferrin glycans can provide the sole source of carbon and energy for growth in defined media. 25139987 6 36 theme transferrin 903:913 arg1 deglycosylation 915:929 transferrin deglycosylation 903:929 transferrin deglycosylation 903:929 We then showed that transferrin deglycosylation occurs in vivo when B. fragilis is propagated in the rat tissue cage model of extraintestinal growth, and that this ability provides a competitive advantage in vivo over strains lacking the don locus. 25139987 6 37 theme cage 995:998 arg1 model 1000:1004 the rat tissue cage model 980:1004 the rat tissue cage model of extraintestinal growth 980:1030 We then showed that transferrin deglycosylation occurs in vivo when B. fragilis is propagated in the rat tissue cage model of extraintestinal growth, and that this ability provides a competitive advantage in vivo over strains lacking the don locus. 25139987 1 38 theme Bacteroides 131:141 arg1 fragilis 143:150 Bacteroides fragilis 131:150 Bacteroides fragilis 131:150 Bacteroides fragilis is the most common anaerobe isolated from clinical infections, and in this report we demonstrate a characteristic of the species that is critical to their success as an opportunistic pathogen. 25139987 1 38 theme Bacteroides 131:141 arg1 anaerobe 171:178 the most common anaerobe 155:178 the most common anaerobe isolated from clinical infections 155:212 Bacteroides fragilis is the most common anaerobe isolated from clinical infections, and in this report we demonstrate a characteristic of the species that is critical to their success as an opportunistic pathogen. 25139987 6 39 theme tissue 988:993 arg1 model 1000:1004 the rat tissue cage model 980:1004 the rat tissue cage model of extraintestinal growth 980:1030 We then showed that transferrin deglycosylation occurs in vivo when B. fragilis is propagated in the rat tissue cage model of extraintestinal growth, and that this ability provides a competitive advantage in vivo over strains lacking the don locus. 25139987 6 40 theme don 1121:1123 arg1 locus 1125:1129 the don locus 1117:1129 the don locus 1117:1129 We then showed that transferrin deglycosylation occurs in vivo when B. fragilis is propagated in the rat tissue cage model of extraintestinal growth, and that this ability provides a competitive advantage in vivo over strains lacking the don locus. 25139987 6 41 theme competitive 1066:1076 arg1 advantage 1078:1086 a competitive advantage 1064:1086 a competitive advantage 1064:1086 We then showed that transferrin deglycosylation occurs in vivo when B. fragilis is propagated in the rat tissue cage model of extraintestinal growth, and that this ability provides a competitive advantage in vivo over strains lacking the don locus. 25139987 6 42 theme rat 984:986 arg1 model 1000:1004 the rat tissue cage model 980:1004 the rat tissue cage model of extraintestinal growth 980:1030 We then showed that transferrin deglycosylation occurs in vivo when B. fragilis is propagated in the rat tissue cage model of extraintestinal growth, and that this ability provides a competitive advantage in vivo over strains lacking the don locus. 25139987 0 43 from fragilis 91:98 arg1 infections 119:128 extraintestinal infections 103:128 extraintestinal infections 103:128 Efficient utilization of complex N-linked glycans is a selective advantage for Bacteroides fragilis in extraintestinal infections. 25139987 3 44 from ability 411:417 arg1 glycoproteins 479:491 the glycoproteins 475:491 the glycoproteins common to serum and serous fluid 475:524 in the gut, B. fragilis has the unique ability of efficiently harvesting complex N-linked glycans from the glycoproteins common to serum and serous fluid. 25139987 5 45 theme carbon 836:841 arg1 source 826:831 the sole source 817:831 the sole source of carbon and energy for growth in defined media 817:880 Using the abundant serum glycoprotein transferrin as a model, it has been shown that B. fragilis alone can rapidly and efficiently deglycosylate this protein in vitro and that transferrin glycans can provide the sole source of carbon and energy for growth in defined media. 25139987 4 46 theme protein 574:580 arg1 complex 582:588 an outer membrane protein complex 556:588 an outer membrane protein complex designated as Don 556:606 This activity is mediated by an outer membrane protein complex designated as Don. 25139987 0 47 theme selective 55:63 arg1 advantage 65:73 a selective advantage 53:73 a selective advantage for Bacteroides fragilis in extraintestinal infections 53:128 Efficient utilization of complex N-linked glycans is a selective advantage for Bacteroides fragilis in extraintestinal infections. 25139987 0 47 theme selective 55:63 arg1 utilization 10:20 Efficient utilization 0:20 Efficient utilization of complex N-linked glycans 0:48 Efficient utilization of complex N-linked glycans is a selective advantage for Bacteroides fragilis in extraintestinal infections. 25139987 1 48 theme opportunistic 321:333 arg1 pathogen 335:342 an opportunistic pathogen 318:342 an opportunistic pathogen 318:342 Bacteroides fragilis is the most common anaerobe isolated from clinical infections, and in this report we demonstrate a characteristic of the species that is critical to their success as an opportunistic pathogen. 25139987 3 49 theme serous 513:518 arg1 fluid 520:524 serous fluid 513:524 serous fluid 513:524 in the gut, B. fragilis has the unique ability of efficiently harvesting complex N-linked glycans from the glycoproteins common to serum and serous fluid. 29218181 2 0 theme electron 403:410 arg1 transfer 412:419 reversible electron transfer 392:419 reversible electron transfer 392:419 Nevertheless, acid/base-responsive organic materials that exhibit reversible electron transfer have not been well studied and developed, owing to the difficulty in inventing a mechanism to associate acid/base stimuli and electron transfer. 29218181 1 1 theme chemical 279:286 arg1 synthesis 288:296 chemical synthesis 279:296 chemical synthesis 279:296 Regulation of electron transfer on organic substances by external stimuli is a fundamental issue in science and technology, which affects organic materials, chemical synthesis, and biological metabolism. 29218181 6 2 theme species 1609:1615 arg1 balance 1659:1665 the balance 1655:1665 the balance of the redox potentials 1655:1689 This highly reversible electron transfer reaction is possible due to the association between the acid stimulus and electron transfer via the acid-regulated N-N bond cleavage/formation reactions which provide an efficient switching mechanism, the ability of the organic molecules to act as multi-electron donors and acceptors, the extraordinary stability of the radical species, the highly selective reactivity, and the balance of the redox potentials. 29218181 6 2 theme species 1609:1615 arg1 stability 1584:1592 the extraordinary stability 1566:1592 the extraordinary stability of the radical species 1566:1615 This highly reversible electron transfer reaction is possible due to the association between the acid stimulus and electron transfer via the acid-regulated N-N bond cleavage/formation reactions which provide an efficient switching mechanism, the ability of the organic molecules to act as multi-electron donors and acceptors, the extraordinary stability of the radical species, the highly selective reactivity, and the balance of the redox potentials. 29218181 6 2 theme species 1609:1615 arg1 mechanism 1471:1479 an efficient switching mechanism 1448:1479 an efficient switching mechanism 1448:1479 This highly reversible electron transfer reaction is possible due to the association between the acid stimulus and electron transfer via the acid-regulated N-N bond cleavage/formation reactions which provide an efficient switching mechanism, the ability of the organic molecules to act as multi-electron donors and acceptors, the extraordinary stability of the radical species, the highly selective reactivity, and the balance of the redox potentials. 29218181 6 2 theme species 1609:1615 arg1 ability 1486:1492 the ability 1482:1492 the ability of the organic molecules to act as multi-electron donors and acceptors 1482:1563 This highly reversible electron transfer reaction is possible due to the association between the acid stimulus and electron transfer via the acid-regulated N-N bond cleavage/formation reactions which provide an efficient switching mechanism, the ability of the organic molecules to act as multi-electron donors and acceptors, the extraordinary stability of the radical species, the highly selective reactivity, and the balance of the redox potentials. 29218181 6 2 theme species 1609:1615 arg1 reactivity 1639:1648 the highly selective reactivity 1618:1648 the highly selective reactivity 1618:1648 This highly reversible electron transfer reaction is possible due to the association between the acid stimulus and electron transfer via the acid-regulated N-N bond cleavage/formation reactions which provide an efficient switching mechanism, the ability of the organic molecules to act as multi-electron donors and acceptors, the extraordinary stability of the radical species, the highly selective reactivity, and the balance of the redox potentials. 29218181 3 3 theme radical 762:768 arg1 cations 770:776 their stable radical cations 749:776 their stable radical cations 749:776 We discovered a new phenomenon in which N-N linked bicarbazole (BC) and tetramethylbiacridine (TBA) derivatives undergo electron transfer disproportionation by acid stimulus, forming their stable radical cations and reduced species. 29218181 3 4 theme new 582:584 arg1 phenomenon 586:595 a new phenomenon 580:595 a new phenomenon in which N-N linked bicarbazole (BC) and tetramethylbiacridine (TBA) derivatives undergo electron transfer disproportionation by acid stimulus, forming their stable radical cations and reduced species 580:796 We discovered a new phenomenon in which N-N linked bicarbazole (BC) and tetramethylbiacridine (TBA) derivatives undergo electron transfer disproportionation by acid stimulus, forming their stable radical cations and reduced species. 29218181 1 5 theme fundamental 201:211 arg1 issue 213:217 a fundamental issue 199:217 a fundamental issue in science and technology, which affects organic materials 199:276 Regulation of electron transfer on organic substances by external stimuli is a fundamental issue in science and technology, which affects organic materials, chemical synthesis, and biological metabolism. 29218181 1 5 theme fundamental 201:211 arg1 Regulation 122:131 Regulation 122:131 Regulation of electron transfer on organic substances by external stimuli 122:194 Regulation of electron transfer on organic substances by external stimuli is a fundamental issue in science and technology, which affects organic materials, chemical synthesis, and biological metabolism. 29218181 2 6 theme acid/base-responsive 340:359 arg1 materials 369:377 acid/base-responsive organic materials 340:377 acid/base-responsive organic materials that exhibit reversible electron transfer 340:419 Nevertheless, acid/base-responsive organic materials that exhibit reversible electron transfer have not been well studied and developed, owing to the difficulty in inventing a mechanism to associate acid/base stimuli and electron transfer. 29218181 3 7 theme N-N 606:608 arg1 BC 630:631 BC 630:631 BC 630:631 We discovered a new phenomenon in which N-N linked bicarbazole (BC) and tetramethylbiacridine (TBA) derivatives undergo electron transfer disproportionation by acid stimulus, forming their stable radical cations and reduced species. 29218181 3 7 theme N-N 606:608 arg1 bicarbazole 617:627 N-N linked bicarbazole 606:627 N-N linked bicarbazole (BC) 606:632 We discovered a new phenomenon in which N-N linked bicarbazole (BC) and tetramethylbiacridine (TBA) derivatives undergo electron transfer disproportionation by acid stimulus, forming their stable radical cations and reduced species. 29218181 4 8 theme electron 974:981 arg1 reactions 992:1000 electron transfer reactions 974:1000 electron transfer reactions with two equivalents of BC or TBA 974:1034 The reaction occurs through a biradical intermediate generated by the acid-triggered N-N bond cleavage reaction of BC or TBA, which acts as a two electron acceptor to undergo electron transfer reactions with two equivalents of BC or TBA. 29218181 5 9 theme N-N 1210:1212 arg1 formation 1219:1227 N-N bond formation 1210:1227 N-N bond formation 1210:1227 In addition, in the case of TBA the disproportionation reaction is highly reversible through neutralization with NEt3, which recovers TBA through back electron transfer and N-N bond formation reactions. 29218181 6 10 theme electron 1263:1270 arg1 reaction 1281:1288 This highly reversible electron transfer reaction 1240:1288 This highly reversible electron transfer reaction 1240:1288 This highly reversible electron transfer reaction is possible due to the association between the acid stimulus and electron transfer via the acid-regulated N-N bond cleavage/formation reactions which provide an efficient switching mechanism, the ability of the organic molecules to act as multi-electron donors and acceptors, the extraordinary stability of the radical species, the highly selective reactivity, and the balance of the redox potentials. 29218181 4 11 theme electron 945:952 arg1 BC 914:915 BC 914:915 BC 914:915 The reaction occurs through a biradical intermediate generated by the acid-triggered N-N bond cleavage reaction of BC or TBA, which acts as a two electron acceptor to undergo electron transfer reactions with two equivalents of BC or TBA. 29218181 4 11 theme electron 945:952 arg1 TBA 920:922 TBA 920:922 TBA 920:922 The reaction occurs through a biradical intermediate generated by the acid-triggered N-N bond cleavage reaction of BC or TBA, which acts as a two electron acceptor to undergo electron transfer reactions with two equivalents of BC or TBA. 29218181 4 11 theme electron 945:952 arg1 acceptor 954:961 a two electron acceptor 939:961 a two electron acceptor 939:961 The reaction occurs through a biradical intermediate generated by the acid-triggered N-N bond cleavage reaction of BC or TBA, which acts as a two electron acceptor to undergo electron transfer reactions with two equivalents of BC or TBA. 29218181 6 12 theme acid 1337:1340 arg1 stimulus 1342:1349 the acid stimulus and electron transfer 1333:1371 stimulus 1342:1349 This highly reversible electron transfer reaction is possible due to the association between the acid stimulus and electron transfer via the acid-regulated N-N bond cleavage/formation reactions which provide an efficient switching mechanism, the ability of the organic molecules to act as multi-electron donors and acceptors, the extraordinary stability of the radical species, the highly selective reactivity, and the balance of the redox potentials. 29218181 6 13 theme selective 1629:1637 arg1 reactivity 1639:1648 the highly selective reactivity 1618:1648 the highly selective reactivity 1618:1648 This highly reversible electron transfer reaction is possible due to the association between the acid stimulus and electron transfer via the acid-regulated N-N bond cleavage/formation reactions which provide an efficient switching mechanism, the ability of the organic molecules to act as multi-electron donors and acceptors, the extraordinary stability of the radical species, the highly selective reactivity, and the balance of the redox potentials. 29218181 2 14 theme electron 547:554 arg1 transfer 556:563 electron transfer 547:563 electron transfer 547:563 Nevertheless, acid/base-responsive organic materials that exhibit reversible electron transfer have not been well studied and developed, owing to the difficulty in inventing a mechanism to associate acid/base stimuli and electron transfer. 29218181 5 15 with neutralization 1130:1143 arg1 NEt3 1150:1153 NEt3 1150:1153 NEt3 1150:1153 In addition, in the case of TBA the disproportionation reaction is highly reversible through neutralization with NEt3, which recovers TBA through back electron transfer and N-N bond formation reactions. 29218181 1 16 theme external 179:186 arg1 stimuli 188:194 external stimuli 179:194 external stimuli 179:194 Regulation of electron transfer on organic substances by external stimuli is a fundamental issue in science and technology, which affects organic materials, chemical synthesis, and biological metabolism. 29218181 3 17 link linked 610:615 arg1 BC 630:631 BC 630:631 BC 630:631 We discovered a new phenomenon in which N-N linked bicarbazole (BC) and tetramethylbiacridine (TBA) derivatives undergo electron transfer disproportionation by acid stimulus, forming their stable radical cations and reduced species. 29218181 3 17 link linked 610:615 arg1 bicarbazole 617:627 N-N linked bicarbazole 606:627 N-N linked bicarbazole (BC) 606:632 We discovered a new phenomenon in which N-N linked bicarbazole (BC) and tetramethylbiacridine (TBA) derivatives undergo electron transfer disproportionation by acid stimulus, forming their stable radical cations and reduced species. 29218181 0 18 theme biacridine 98:107 arg1 derivatives 109:119 biacridine derivatives 98:119 biacridine derivatives 98:119 Acid/base-regulated reversible electron transfer disproportionation of N-N linked bicarbazole and biacridine derivatives. 29218181 3 19 dep bicarbazole 617:627 arg1 derivatives 666:676 derivatives 666:676 derivatives 666:676 We discovered a new phenomenon in which N-N linked bicarbazole (BC) and tetramethylbiacridine (TBA) derivatives undergo electron transfer disproportionation by acid stimulus, forming their stable radical cations and reduced species. 29218181 7 20 theme transfer 1777:1784 arg1 systems 1786:1792 acid/base-regulated organic electron transfer systems 1740:1792 acid/base-regulated organic electron transfer systems 1740:1792 This discovery provides new design concepts for acid/base-regulated organic electron transfer systems, chemical reagents, or organic materials. 29218181 6 21 theme cleavage/formation 1405:1422 arg1 reactions 1424:1432 the acid-regulated N-N bond cleavage/formation reactions 1377:1432 the acid-regulated N-N bond cleavage/formation reactions which provide an efficient switching mechanism, the ability of the organic molecules to act as multi-electron donors and acceptors, the extraordinary stability of the radical species, the highly selective reactivity, and the balance of the redox potentials 1377:1689 This highly reversible electron transfer reaction is possible due to the association between the acid stimulus and electron transfer via the acid-regulated N-N bond cleavage/formation reactions which provide an efficient switching mechanism, the ability of the organic molecules to act as multi-electron donors and acceptors, the extraordinary stability of the radical species, the highly selective reactivity, and the balance of the redox potentials. 29218181 7 22 theme organic 1760:1766 arg1 systems 1786:1792 acid/base-regulated organic electron transfer systems 1740:1792 acid/base-regulated organic electron transfer systems 1740:1792 This discovery provides new design concepts for acid/base-regulated organic electron transfer systems, chemical reagents, or organic materials. 29218181 5 23 dep transfer 1197:1204 arg1 reactions 1229:1237 reactions 1229:1237 reactions 1229:1237 In addition, in the case of TBA the disproportionation reaction is highly reversible through neutralization with NEt3, which recovers TBA through back electron transfer and N-N bond formation reactions. 29218181 4 24 theme biradical 829:837 arg1 intermediate 839:850 a biradical intermediate 827:850 a biradical intermediate generated by the acid-triggered N-N bond cleavage reaction of BC or TBA, which acts as a two electron acceptor to undergo electron transfer reactions with two equivalents of BC or TBA 827:1034 The reaction occurs through a biradical intermediate generated by the acid-triggered N-N bond cleavage reaction of BC or TBA, which acts as a two electron acceptor to undergo electron transfer reactions with two equivalents of BC or TBA. 29218181 6 25 theme N-N 1396:1398 arg1 reactions 1424:1432 the acid-regulated N-N bond cleavage/formation reactions 1377:1432 the acid-regulated N-N bond cleavage/formation reactions which provide an efficient switching mechanism, the ability of the organic molecules to act as multi-electron donors and acceptors, the extraordinary stability of the radical species, the highly selective reactivity, and the balance of the redox potentials 1377:1689 This highly reversible electron transfer reaction is possible due to the association between the acid stimulus and electron transfer via the acid-regulated N-N bond cleavage/formation reactions which provide an efficient switching mechanism, the ability of the organic molecules to act as multi-electron donors and acceptors, the extraordinary stability of the radical species, the highly selective reactivity, and the balance of the redox potentials. 29218181 6 26 theme redox 1674:1678 arg1 potentials 1680:1689 the redox potentials 1670:1689 the redox potentials 1670:1689 This highly reversible electron transfer reaction is possible due to the association between the acid stimulus and electron transfer via the acid-regulated N-N bond cleavage/formation reactions which provide an efficient switching mechanism, the ability of the organic molecules to act as multi-electron donors and acceptors, the extraordinary stability of the radical species, the highly selective reactivity, and the balance of the redox potentials. 29218181 0 27 theme Acid/base-regulated 0:18 arg1 disproportionation 49:66 Acid/base-regulated reversible electron transfer disproportionation 0:66 Acid/base-regulated reversible electron transfer disproportionation of N-N 0:73 Acid/base-regulated reversible electron transfer disproportionation of N-N linked bicarbazole and biacridine derivatives. 29218181 7 28 theme design 1720:1725 arg1 concepts 1727:1734 new design concepts 1716:1734 new design concepts for acid/base-regulated organic electron transfer systems, chemical reagents, or organic materials 1716:1833 This discovery provides new design concepts for acid/base-regulated organic electron transfer systems, chemical reagents, or organic materials. 29218181 0 29 theme electron 31:38 arg1 transfer 40:47 reversible electron transfer 20:47 Acid/base-regulated reversible electron transfer disproportionation of N-N 0:73 Acid/base-regulated reversible electron transfer disproportionation of N-N linked bicarbazole and biacridine derivatives. 29218181 5 30 theme bond 1214:1217 arg1 formation 1219:1227 N-N bond formation 1210:1227 N-N bond formation 1210:1227 In addition, in the case of TBA the disproportionation reaction is highly reversible through neutralization with NEt3, which recovers TBA through back electron transfer and N-N bond formation reactions. 29218181 1 31 theme electron 136:143 arg1 transfer 145:152 electron transfer 136:152 electron transfer 136:152 Regulation of electron transfer on organic substances by external stimuli is a fundamental issue in science and technology, which affects organic materials, chemical synthesis, and biological metabolism. 29218181 6 32 theme radical 1601:1607 arg1 species 1609:1615 the radical species 1597:1615 the radical species 1597:1615 This highly reversible electron transfer reaction is possible due to the association between the acid stimulus and electron transfer via the acid-regulated N-N bond cleavage/formation reactions which provide an efficient switching mechanism, the ability of the organic molecules to act as multi-electron donors and acceptors, the extraordinary stability of the radical species, the highly selective reactivity, and the balance of the redox potentials. 29218181 3 33 theme transfer 695:702 arg1 disproportionation 704:721 electron transfer disproportionation 686:721 electron transfer disproportionation 686:721 We discovered a new phenomenon in which N-N linked bicarbazole (BC) and tetramethylbiacridine (TBA) derivatives undergo electron transfer disproportionation by acid stimulus, forming their stable radical cations and reduced species. 29218181 4 34 theme N-N 884:886 arg1 reaction 902:909 the acid-triggered N-N bond cleavage reaction 865:909 the acid-triggered N-N bond cleavage reaction of BC or TBA, which acts as a two electron acceptor to undergo electron transfer reactions with two equivalents of BC or TBA 865:1034 The reaction occurs through a biradical intermediate generated by the acid-triggered N-N bond cleavage reaction of BC or TBA, which acts as a two electron acceptor to undergo electron transfer reactions with two equivalents of BC or TBA. 29218181 4 35 theme cleavage 893:900 arg1 reaction 902:909 the acid-triggered N-N bond cleavage reaction 865:909 the acid-triggered N-N bond cleavage reaction of BC or TBA, which acts as a two electron acceptor to undergo electron transfer reactions with two equivalents of BC or TBA 865:1034 The reaction occurs through a biradical intermediate generated by the acid-triggered N-N bond cleavage reaction of BC or TBA, which acts as a two electron acceptor to undergo electron transfer reactions with two equivalents of BC or TBA. 29218181 2 36 theme reversible 392:401 arg1 transfer 412:419 reversible electron transfer 392:419 reversible electron transfer 392:419 Nevertheless, acid/base-responsive organic materials that exhibit reversible electron transfer have not been well studied and developed, owing to the difficulty in inventing a mechanism to associate acid/base stimuli and electron transfer. 29218181 0 37 theme N-N 71:73 arg1 disproportionation 49:66 Acid/base-regulated reversible electron transfer disproportionation 0:66 Acid/base-regulated reversible electron transfer disproportionation of N-N 0:73 Acid/base-regulated reversible electron transfer disproportionation of N-N linked bicarbazole and biacridine derivatives. 29218181 5 38 theme electron 1188:1195 arg1 transfer 1197:1204 electron transfer 1188:1204 electron transfer 1188:1204 In addition, in the case of TBA the disproportionation reaction is highly reversible through neutralization with NEt3, which recovers TBA through back electron transfer and N-N bond formation reactions. 29218181 6 39 theme multi-electron 1529:1542 arg1 donors 1544:1549 multi-electron donors 1529:1549 multi-electron donors 1529:1549 This highly reversible electron transfer reaction is possible due to the association between the acid stimulus and electron transfer via the acid-regulated N-N bond cleavage/formation reactions which provide an efficient switching mechanism, the ability of the organic molecules to act as multi-electron donors and acceptors, the extraordinary stability of the radical species, the highly selective reactivity, and the balance of the redox potentials. 29218181 1 40 theme organic 260:266 arg1 materials 268:276 organic materials 260:276 organic materials 260:276 Regulation of electron transfer on organic substances by external stimuli is a fundamental issue in science and technology, which affects organic materials, chemical synthesis, and biological metabolism. 29218181 4 41 with reactions 992:1000 arg1 equivalents 1011:1021 two equivalents 1007:1021 two equivalents of BC or TBA 1007:1034 The reaction occurs through a biradical intermediate generated by the acid-triggered N-N bond cleavage reaction of BC or TBA, which acts as a two electron acceptor to undergo electron transfer reactions with two equivalents of BC or TBA. 29218181 3 42 theme stable 755:760 arg1 cations 770:776 their stable radical cations 749:776 their stable radical cations 749:776 We discovered a new phenomenon in which N-N linked bicarbazole (BC) and tetramethylbiacridine (TBA) derivatives undergo electron transfer disproportionation by acid stimulus, forming their stable radical cations and reduced species. 29218181 4 43 theme TBA 920:922 arg1 reaction 902:909 the acid-triggered N-N bond cleavage reaction 865:909 the acid-triggered N-N bond cleavage reaction of BC or TBA, which acts as a two electron acceptor to undergo electron transfer reactions with two equivalents of BC or TBA 865:1034 The reaction occurs through a biradical intermediate generated by the acid-triggered N-N bond cleavage reaction of BC or TBA, which acts as a two electron acceptor to undergo electron transfer reactions with two equivalents of BC or TBA. 29218181 6 44 theme molecules 1509:1517 arg1 balance 1659:1665 the balance 1655:1665 the balance of the redox potentials 1655:1689 This highly reversible electron transfer reaction is possible due to the association between the acid stimulus and electron transfer via the acid-regulated N-N bond cleavage/formation reactions which provide an efficient switching mechanism, the ability of the organic molecules to act as multi-electron donors and acceptors, the extraordinary stability of the radical species, the highly selective reactivity, and the balance of the redox potentials. 29218181 6 44 theme molecules 1509:1517 arg1 stability 1584:1592 the extraordinary stability 1566:1592 the extraordinary stability of the radical species 1566:1615 This highly reversible electron transfer reaction is possible due to the association between the acid stimulus and electron transfer via the acid-regulated N-N bond cleavage/formation reactions which provide an efficient switching mechanism, the ability of the organic molecules to act as multi-electron donors and acceptors, the extraordinary stability of the radical species, the highly selective reactivity, and the balance of the redox potentials. 29218181 6 44 theme molecules 1509:1517 arg1 mechanism 1471:1479 an efficient switching mechanism 1448:1479 an efficient switching mechanism 1448:1479 This highly reversible electron transfer reaction is possible due to the association between the acid stimulus and electron transfer via the acid-regulated N-N bond cleavage/formation reactions which provide an efficient switching mechanism, the ability of the organic molecules to act as multi-electron donors and acceptors, the extraordinary stability of the radical species, the highly selective reactivity, and the balance of the redox potentials. 29218181 6 44 theme molecules 1509:1517 arg1 ability 1486:1492 the ability 1482:1492 the ability of the organic molecules to act as multi-electron donors and acceptors 1482:1563 This highly reversible electron transfer reaction is possible due to the association between the acid stimulus and electron transfer via the acid-regulated N-N bond cleavage/formation reactions which provide an efficient switching mechanism, the ability of the organic molecules to act as multi-electron donors and acceptors, the extraordinary stability of the radical species, the highly selective reactivity, and the balance of the redox potentials. 29218181 6 44 theme molecules 1509:1517 arg1 reactivity 1639:1648 the highly selective reactivity 1618:1648 the highly selective reactivity 1618:1648 This highly reversible electron transfer reaction is possible due to the association between the acid stimulus and electron transfer via the acid-regulated N-N bond cleavage/formation reactions which provide an efficient switching mechanism, the ability of the organic molecules to act as multi-electron donors and acceptors, the extraordinary stability of the radical species, the highly selective reactivity, and the balance of the redox potentials. 29218181 2 45 theme organic 361:367 arg1 materials 369:377 acid/base-responsive organic materials 340:377 acid/base-responsive organic materials that exhibit reversible electron transfer 340:419 Nevertheless, acid/base-responsive organic materials that exhibit reversible electron transfer have not been well studied and developed, owing to the difficulty in inventing a mechanism to associate acid/base stimuli and electron transfer. 29218181 3 46 theme reduced 782:788 arg1 species 790:796 reduced species 782:796 reduced species 782:796 We discovered a new phenomenon in which N-N linked bicarbazole (BC) and tetramethylbiacridine (TBA) derivatives undergo electron transfer disproportionation by acid stimulus, forming their stable radical cations and reduced species. 29218181 1 47 from metabolism 314:323 arg1 technology 234:243 technology 234:243 technology 234:243 Regulation of electron transfer on organic substances by external stimuli is a fundamental issue in science and technology, which affects organic materials, chemical synthesis, and biological metabolism. 29218181 1 47 from metabolism 314:323 arg1 science 222:228 science 222:228 science 222:228 Regulation of electron transfer on organic substances by external stimuli is a fundamental issue in science and technology, which affects organic materials, chemical synthesis, and biological metabolism. 29218181 5 48 from addition 1040:1047 arg1 reaction 1092:1099 the disproportionation reaction 1069:1099 the disproportionation reaction 1069:1099 In addition, in the case of TBA the disproportionation reaction is highly reversible through neutralization with NEt3, which recovers TBA through back electron transfer and N-N bond formation reactions. 29218181 5 48 from addition 1040:1047 arg1 reversible 1111:1120 reversible 1111:1120 reversible 1111:1120 In addition, in the case of TBA the disproportionation reaction is highly reversible through neutralization with NEt3, which recovers TBA through back electron transfer and N-N bond formation reactions. 29218181 6 49 theme switching 1461:1469 arg1 mechanism 1471:1479 an efficient switching mechanism 1448:1479 an efficient switching mechanism 1448:1479 This highly reversible electron transfer reaction is possible due to the association between the acid stimulus and electron transfer via the acid-regulated N-N bond cleavage/formation reactions which provide an efficient switching mechanism, the ability of the organic molecules to act as multi-electron donors and acceptors, the extraordinary stability of the radical species, the highly selective reactivity, and the balance of the redox potentials. 29218181 4 50 theme BC 1026:1027 arg1 equivalents 1011:1021 two equivalents 1007:1021 two equivalents of BC or TBA 1007:1034 The reaction occurs through a biradical intermediate generated by the acid-triggered N-N bond cleavage reaction of BC or TBA, which acts as a two electron acceptor to undergo electron transfer reactions with two equivalents of BC or TBA. 29218181 3 51 theme linked 610:615 arg1 BC 630:631 BC 630:631 BC 630:631 We discovered a new phenomenon in which N-N linked bicarbazole (BC) and tetramethylbiacridine (TBA) derivatives undergo electron transfer disproportionation by acid stimulus, forming their stable radical cations and reduced species. 29218181 3 51 theme linked 610:615 arg1 bicarbazole 617:627 N-N linked bicarbazole 606:627 N-N linked bicarbazole (BC) 606:632 We discovered a new phenomenon in which N-N linked bicarbazole (BC) and tetramethylbiacridine (TBA) derivatives undergo electron transfer disproportionation by acid stimulus, forming their stable radical cations and reduced species. 29218181 1 52 from Regulation 122:131 arg1 substances 165:174 organic substances 157:174 organic substances 157:174 Regulation of electron transfer on organic substances by external stimuli is a fundamental issue in science and technology, which affects organic materials, chemical synthesis, and biological metabolism. 29218181 4 53 theme BC 914:915 arg1 reaction 902:909 the acid-triggered N-N bond cleavage reaction 865:909 the acid-triggered N-N bond cleavage reaction of BC or TBA, which acts as a two electron acceptor to undergo electron transfer reactions with two equivalents of BC or TBA 865:1034 The reaction occurs through a biradical intermediate generated by the acid-triggered N-N bond cleavage reaction of BC or TBA, which acts as a two electron acceptor to undergo electron transfer reactions with two equivalents of BC or TBA. 29218181 1 54 from synthesis 288:296 arg1 technology 234:243 technology 234:243 technology 234:243 Regulation of electron transfer on organic substances by external stimuli is a fundamental issue in science and technology, which affects organic materials, chemical synthesis, and biological metabolism. 29218181 1 54 from synthesis 288:296 arg1 science 222:228 science 222:228 science 222:228 Regulation of electron transfer on organic substances by external stimuli is a fundamental issue in science and technology, which affects organic materials, chemical synthesis, and biological metabolism. 29218181 5 55 from case 1057:1060 arg1 reaction 1092:1099 the disproportionation reaction 1069:1099 the disproportionation reaction 1069:1099 In addition, in the case of TBA the disproportionation reaction is highly reversible through neutralization with NEt3, which recovers TBA through back electron transfer and N-N bond formation reactions. 29218181 5 55 from case 1057:1060 arg1 reversible 1111:1120 reversible 1111:1120 reversible 1111:1120 In addition, in the case of TBA the disproportionation reaction is highly reversible through neutralization with NEt3, which recovers TBA through back electron transfer and N-N bond formation reactions. 29218181 6 56 theme transfer 1272:1279 arg1 reaction 1281:1288 This highly reversible electron transfer reaction 1240:1288 This highly reversible electron transfer reaction 1240:1288 This highly reversible electron transfer reaction is possible due to the association between the acid stimulus and electron transfer via the acid-regulated N-N bond cleavage/formation reactions which provide an efficient switching mechanism, the ability of the organic molecules to act as multi-electron donors and acceptors, the extraordinary stability of the radical species, the highly selective reactivity, and the balance of the redox potentials. 29218181 6 57 theme electron 1355:1362 arg1 transfer 1364:1371 the acid stimulus and electron transfer 1333:1371 transfer 1364:1371 This highly reversible electron transfer reaction is possible due to the association between the acid stimulus and electron transfer via the acid-regulated N-N bond cleavage/formation reactions which provide an efficient switching mechanism, the ability of the organic molecules to act as multi-electron donors and acceptors, the extraordinary stability of the radical species, the highly selective reactivity, and the balance of the redox potentials. 29218181 1 58 theme transfer 145:152 arg1 issue 213:217 a fundamental issue 199:217 a fundamental issue in science and technology, which affects organic materials 199:276 Regulation of electron transfer on organic substances by external stimuli is a fundamental issue in science and technology, which affects organic materials, chemical synthesis, and biological metabolism. 29218181 1 58 theme transfer 145:152 arg1 Regulation 122:131 Regulation 122:131 Regulation of electron transfer on organic substances by external stimuli 122:194 Regulation of electron transfer on organic substances by external stimuli is a fundamental issue in science and technology, which affects organic materials, chemical synthesis, and biological metabolism. 29218181 6 59 theme acid-regulated 1381:1394 arg1 reactions 1424:1432 the acid-regulated N-N bond cleavage/formation reactions 1377:1432 the acid-regulated N-N bond cleavage/formation reactions which provide an efficient switching mechanism, the ability of the organic molecules to act as multi-electron donors and acceptors, the extraordinary stability of the radical species, the highly selective reactivity, and the balance of the redox potentials 1377:1689 This highly reversible electron transfer reaction is possible due to the association between the acid stimulus and electron transfer via the acid-regulated N-N bond cleavage/formation reactions which provide an efficient switching mechanism, the ability of the organic molecules to act as multi-electron donors and acceptors, the extraordinary stability of the radical species, the highly selective reactivity, and the balance of the redox potentials. 29218181 6 60 theme reversible 1252:1261 arg1 reaction 1281:1288 This highly reversible electron transfer reaction 1240:1288 This highly reversible electron transfer reaction 1240:1288 This highly reversible electron transfer reaction is possible due to the association between the acid stimulus and electron transfer via the acid-regulated N-N bond cleavage/formation reactions which provide an efficient switching mechanism, the ability of the organic molecules to act as multi-electron donors and acceptors, the extraordinary stability of the radical species, the highly selective reactivity, and the balance of the redox potentials. 29218181 5 61 theme TBA 1065:1067 arg1 case 1057:1060 the case 1053:1060 the case of TBA 1053:1067 In addition, in the case of TBA the disproportionation reaction is highly reversible through neutralization with NEt3, which recovers TBA through back electron transfer and N-N bond formation reactions. 29218181 1 62 theme organic 157:163 arg1 substances 165:174 organic substances 157:174 organic substances 157:174 Regulation of electron transfer on organic substances by external stimuli is a fundamental issue in science and technology, which affects organic materials, chemical synthesis, and biological metabolism. 29218181 7 63 theme organic 1817:1823 arg1 materials 1825:1833 organic materials 1817:1833 organic materials 1817:1833 This discovery provides new design concepts for acid/base-regulated organic electron transfer systems, chemical reagents, or organic materials. 29218181 6 64 theme extraordinary 1570:1582 arg1 stability 1584:1592 the extraordinary stability 1566:1592 the extraordinary stability of the radical species 1566:1615 This highly reversible electron transfer reaction is possible due to the association between the acid stimulus and electron transfer via the acid-regulated N-N bond cleavage/formation reactions which provide an efficient switching mechanism, the ability of the organic molecules to act as multi-electron donors and acceptors, the extraordinary stability of the radical species, the highly selective reactivity, and the balance of the redox potentials. 29218181 6 65 theme efficient 1451:1459 arg1 mechanism 1471:1479 an efficient switching mechanism 1448:1479 an efficient switching mechanism 1448:1479 This highly reversible electron transfer reaction is possible due to the association between the acid stimulus and electron transfer via the acid-regulated N-N bond cleavage/formation reactions which provide an efficient switching mechanism, the ability of the organic molecules to act as multi-electron donors and acceptors, the extraordinary stability of the radical species, the highly selective reactivity, and the balance of the redox potentials. 29218181 5 66 theme disproportionation 1073:1090 arg1 reaction 1092:1099 the disproportionation reaction 1069:1099 the disproportionation reaction 1069:1099 In addition, in the case of TBA the disproportionation reaction is highly reversible through neutralization with NEt3, which recovers TBA through back electron transfer and N-N bond formation reactions. 29218181 5 66 theme disproportionation 1073:1090 arg1 reversible 1111:1120 reversible 1111:1120 reversible 1111:1120 In addition, in the case of TBA the disproportionation reaction is highly reversible through neutralization with NEt3, which recovers TBA through back electron transfer and N-N bond formation reactions. 29218181 5 67 from reversible 1111:1120 arg1 addition 1040:1047 addition 1040:1047 addition 1040:1047 In addition, in the case of TBA the disproportionation reaction is highly reversible through neutralization with NEt3, which recovers TBA through back electron transfer and N-N bond formation reactions. 29218181 5 67 from reversible 1111:1120 arg1 case 1057:1060 the case 1053:1060 the case of TBA 1053:1067 In addition, in the case of TBA the disproportionation reaction is highly reversible through neutralization with NEt3, which recovers TBA through back electron transfer and N-N bond formation reactions. 29218181 7 68 theme chemical 1795:1802 arg1 reagents 1804:1811 chemical reagents 1795:1811 chemical reagents 1795:1811 This discovery provides new design concepts for acid/base-regulated organic electron transfer systems, chemical reagents, or organic materials. 29218181 2 69 theme acid/base 525:533 arg1 stimuli 535:541 acid/base stimuli 525:541 acid/base stimuli 525:541 Nevertheless, acid/base-responsive organic materials that exhibit reversible electron transfer have not been well studied and developed, owing to the difficulty in inventing a mechanism to associate acid/base stimuli and electron transfer. 29218181 4 70 theme transfer 983:990 arg1 reactions 992:1000 electron transfer reactions 974:1000 electron transfer reactions with two equivalents of BC or TBA 974:1034 The reaction occurs through a biradical intermediate generated by the acid-triggered N-N bond cleavage reaction of BC or TBA, which acts as a two electron acceptor to undergo electron transfer reactions with two equivalents of BC or TBA. 29218181 6 71 theme bond 1400:1403 arg1 reactions 1424:1432 the acid-regulated N-N bond cleavage/formation reactions 1377:1432 the acid-regulated N-N bond cleavage/formation reactions which provide an efficient switching mechanism, the ability of the organic molecules to act as multi-electron donors and acceptors, the extraordinary stability of the radical species, the highly selective reactivity, and the balance of the redox potentials 1377:1689 This highly reversible electron transfer reaction is possible due to the association between the acid stimulus and electron transfer via the acid-regulated N-N bond cleavage/formation reactions which provide an efficient switching mechanism, the ability of the organic molecules to act as multi-electron donors and acceptors, the extraordinary stability of the radical species, the highly selective reactivity, and the balance of the redox potentials. 29218181 6 72 theme potentials 1680:1689 arg1 balance 1659:1665 the balance 1655:1665 the balance of the redox potentials 1655:1689 This highly reversible electron transfer reaction is possible due to the association between the acid stimulus and electron transfer via the acid-regulated N-N bond cleavage/formation reactions which provide an efficient switching mechanism, the ability of the organic molecules to act as multi-electron donors and acceptors, the extraordinary stability of the radical species, the highly selective reactivity, and the balance of the redox potentials. 29218181 6 72 theme potentials 1680:1689 arg1 stability 1584:1592 the extraordinary stability 1566:1592 the extraordinary stability of the radical species 1566:1615 This highly reversible electron transfer reaction is possible due to the association between the acid stimulus and electron transfer via the acid-regulated N-N bond cleavage/formation reactions which provide an efficient switching mechanism, the ability of the organic molecules to act as multi-electron donors and acceptors, the extraordinary stability of the radical species, the highly selective reactivity, and the balance of the redox potentials. 29218181 6 72 theme potentials 1680:1689 arg1 mechanism 1471:1479 an efficient switching mechanism 1448:1479 an efficient switching mechanism 1448:1479 This highly reversible electron transfer reaction is possible due to the association between the acid stimulus and electron transfer via the acid-regulated N-N bond cleavage/formation reactions which provide an efficient switching mechanism, the ability of the organic molecules to act as multi-electron donors and acceptors, the extraordinary stability of the radical species, the highly selective reactivity, and the balance of the redox potentials. 29218181 6 72 theme potentials 1680:1689 arg1 ability 1486:1492 the ability 1482:1492 the ability of the organic molecules to act as multi-electron donors and acceptors 1482:1563 This highly reversible electron transfer reaction is possible due to the association between the acid stimulus and electron transfer via the acid-regulated N-N bond cleavage/formation reactions which provide an efficient switching mechanism, the ability of the organic molecules to act as multi-electron donors and acceptors, the extraordinary stability of the radical species, the highly selective reactivity, and the balance of the redox potentials. 29218181 6 72 theme potentials 1680:1689 arg1 reactivity 1639:1648 the highly selective reactivity 1618:1648 the highly selective reactivity 1618:1648 This highly reversible electron transfer reaction is possible due to the association between the acid stimulus and electron transfer via the acid-regulated N-N bond cleavage/formation reactions which provide an efficient switching mechanism, the ability of the organic molecules to act as multi-electron donors and acceptors, the extraordinary stability of the radical species, the highly selective reactivity, and the balance of the redox potentials. 29218181 7 73 theme electron 1768:1775 arg1 systems 1786:1792 acid/base-regulated organic electron transfer systems 1740:1792 acid/base-regulated organic electron transfer systems 1740:1792 This discovery provides new design concepts for acid/base-regulated organic electron transfer systems, chemical reagents, or organic materials. 29218181 0 74 theme reversible 20:29 arg1 transfer 40:47 reversible electron transfer 20:47 Acid/base-regulated reversible electron transfer disproportionation of N-N 0:73 Acid/base-regulated reversible electron transfer disproportionation of N-N linked bicarbazole and biacridine derivatives. 29218181 7 75 theme acid/base-regulated 1740:1758 arg1 systems 1786:1792 acid/base-regulated organic electron transfer systems 1740:1792 acid/base-regulated organic electron transfer systems 1740:1792 This discovery provides new design concepts for acid/base-regulated organic electron transfer systems, chemical reagents, or organic materials. 29218181 0 76 theme transfer 40:47 arg1 disproportionation 49:66 Acid/base-regulated reversible electron transfer disproportionation 0:66 Acid/base-regulated reversible electron transfer disproportionation of N-N 0:73 Acid/base-regulated reversible electron transfer disproportionation of N-N linked bicarbazole and biacridine derivatives. 29218181 1 77 theme biological 303:312 arg1 metabolism 314:323 biological metabolism 303:323 biological metabolism 303:323 Regulation of electron transfer on organic substances by external stimuli is a fundamental issue in science and technology, which affects organic materials, chemical synthesis, and biological metabolism. 29218181 3 78 theme electron 686:693 arg1 disproportionation 704:721 electron transfer disproportionation 686:721 electron transfer disproportionation 686:721 We discovered a new phenomenon in which N-N linked bicarbazole (BC) and tetramethylbiacridine (TBA) derivatives undergo electron transfer disproportionation by acid stimulus, forming their stable radical cations and reduced species. 29218181 7 79 theme new 1716:1718 arg1 concepts 1727:1734 new design concepts 1716:1734 new design concepts for acid/base-regulated organic electron transfer systems, chemical reagents, or organic materials 1716:1833 This discovery provides new design concepts for acid/base-regulated organic electron transfer systems, chemical reagents, or organic materials. 29218181 4 80 theme TBA 1032:1034 arg1 equivalents 1011:1021 two equivalents 1007:1021 two equivalents of BC or TBA 1007:1034 The reaction occurs through a biradical intermediate generated by the acid-triggered N-N bond cleavage reaction of BC or TBA, which acts as a two electron acceptor to undergo electron transfer reactions with two equivalents of BC or TBA. 29218181 4 81 theme acid-triggered 869:882 arg1 reaction 902:909 the acid-triggered N-N bond cleavage reaction 865:909 the acid-triggered N-N bond cleavage reaction of BC or TBA, which acts as a two electron acceptor to undergo electron transfer reactions with two equivalents of BC or TBA 865:1034 The reaction occurs through a biradical intermediate generated by the acid-triggered N-N bond cleavage reaction of BC or TBA, which acts as a two electron acceptor to undergo electron transfer reactions with two equivalents of BC or TBA. 29218181 1 82 from issue 213:217 arg1 technology 234:243 technology 234:243 technology 234:243 Regulation of electron transfer on organic substances by external stimuli is a fundamental issue in science and technology, which affects organic materials, chemical synthesis, and biological metabolism. 29218181 1 82 from issue 213:217 arg1 science 222:228 science 222:228 science 222:228 Regulation of electron transfer on organic substances by external stimuli is a fundamental issue in science and technology, which affects organic materials, chemical synthesis, and biological metabolism. 29218181 3 83 theme acid 726:729 arg1 stimulus 731:738 acid stimulus 726:738 acid stimulus 726:738 We discovered a new phenomenon in which N-N linked bicarbazole (BC) and tetramethylbiacridine (TBA) derivatives undergo electron transfer disproportionation by acid stimulus, forming their stable radical cations and reduced species. 29218181 4 84 theme bond 888:891 arg1 reaction 902:909 the acid-triggered N-N bond cleavage reaction 865:909 the acid-triggered N-N bond cleavage reaction of BC or TBA, which acts as a two electron acceptor to undergo electron transfer reactions with two equivalents of BC or TBA 865:1034 The reaction occurs through a biradical intermediate generated by the acid-triggered N-N bond cleavage reaction of BC or TBA, which acts as a two electron acceptor to undergo electron transfer reactions with two equivalents of BC or TBA. 29218181 6 85 theme organic 1501:1507 arg1 molecules 1509:1517 the organic molecules 1497:1517 the organic molecules 1497:1517 This highly reversible electron transfer reaction is possible due to the association between the acid stimulus and electron transfer via the acid-regulated N-N bond cleavage/formation reactions which provide an efficient switching mechanism, the ability of the organic molecules to act as multi-electron donors and acceptors, the extraordinary stability of the radical species, the highly selective reactivity, and the balance of the redox potentials. 25652041 0 0 from profiling 23:31 arg1 plant 116:120 a model plant 108:120 a model plant for cereal crops 108:137 N-linked glycoproteome profiling of seedling leaf in Brachypodium distachyon L. Brachypodium distachyon L., a model plant for cereal crops, has become important as an alternative and potential biofuel grass. 25652041 0 0 from profiling 23:31 arg1 L. 104:105 L. 104:105 L. 104:105 N-linked glycoproteome profiling of seedling leaf in Brachypodium distachyon L. Brachypodium distachyon L., a model plant for cereal crops, has become important as an alternative and potential biofuel grass. 25652041 7 1 dep seedling 1415:1422 arg1 leaves 1424:1429 leaves 1424:1429 leaves 1424:1429 The results provide a general overview of protein N-glycosylation modifications during the early growth of seedling leaves in B. distachyon and supplement the glycoproteome databases of plants. 25652041 6 2 theme secretory 1274:1282 arg1 pathways 1284:1291 typical protein secretory pathways 1258:1291 typical protein secretory pathways 1258:1291 Moreover, transmembrane helices and signal peptide prediction showed that most of these glycoproteins could participate in typical protein secretory pathways in eukaryotes. 25652041 1 3 from formation 411:419 arg1 activity 365:372 protein activity 357:372 protein activity 357:372 In plants, N-glycosylation is one of the most common and important protein modifications, playing important roles in signal recognition, increase in protein activity, stability of protein structure, and formation of tissues and organs. 25652041 5 4 theme receptor-like 1060:1072 arg1 kinases 1074:1080 receptor-like kinases 1060:1080 receptor-like kinases 1060:1080 Further functional analysis suggested that some of these identified glycoproteins are involved in signal transduction, protein trafficking, and quality control and the modification and remodeling of cell-wall components such as receptor-like kinases, protein disulfide isomerase, and polygalacturonase. 25652041 2 5 theme glycoproteome 482:494 arg1 analysis 496:503 the first glycoproteome analysis 472:503 the first glycoproteome analysis in the seedling leaves of B. distachyon 472:543 In this study, we performed the first glycoproteome analysis in the seedling leaves of B. distachyon. 25652041 1 6 theme signal 325:330 arg1 recognition 332:342 signal recognition 325:342 signal recognition 325:342 In plants, N-glycosylation is one of the most common and important protein modifications, playing important roles in signal recognition, increase in protein activity, stability of protein structure, and formation of tissues and organs. 25652041 7 7 theme general 1330:1336 arg1 overview 1338:1345 a general overview 1328:1345 a general overview of protein N-glycosylation modifications during the early growth of seedling leaves in B. distachyon 1328:1446 The results provide a general overview of protein N-glycosylation modifications during the early growth of seedling leaves in B. distachyon and supplement the glycoproteome databases of plants. 25652041 5 8 theme protein 951:957 arg1 trafficking 959:969 protein trafficking 951:969 protein trafficking 951:969 Further functional analysis suggested that some of these identified glycoproteins are involved in signal transduction, protein trafficking, and quality control and the modification and remodeling of cell-wall components such as receptor-like kinases, protein disulfide isomerase, and polygalacturonase. 25652041 6 9 theme transmembrane 1145:1157 arg1 helices 1159:1165 transmembrane helices 1145:1165 transmembrane helices 1145:1165 Moreover, transmembrane helices and signal peptide prediction showed that most of these glycoproteins could participate in typical protein secretory pathways in eukaryotes. 25652041 6 10 theme typical 1258:1264 arg1 pathways 1284:1291 typical protein secretory pathways 1258:1291 typical protein secretory pathways 1258:1291 Moreover, transmembrane helices and signal peptide prediction showed that most of these glycoproteins could participate in typical protein secretory pathways in eukaryotes. 25652041 1 11 from stability 375:383 arg1 activity 365:372 protein activity 357:372 protein activity 357:372 In plants, N-glycosylation is one of the most common and important protein modifications, playing important roles in signal recognition, increase in protein activity, stability of protein structure, and formation of tissues and organs. 25652041 5 12 theme disulfide 1091:1099 arg1 isomerase 1101:1109 protein disulfide isomerase 1083:1109 protein disulfide isomerase 1083:1109 Further functional analysis suggested that some of these identified glycoproteins are involved in signal transduction, protein trafficking, and quality control and the modification and remodeling of cell-wall components such as receptor-like kinases, protein disulfide isomerase, and polygalacturonase. 25652041 0 13 theme model 110:114 arg1 plant 116:120 a model plant 108:120 a model plant for cereal crops 108:137 N-linked glycoproteome profiling of seedling leaf in Brachypodium distachyon L. Brachypodium distachyon L., a model plant for cereal crops, has become important as an alternative and potential biofuel grass. 25652041 0 13 theme model 110:114 arg1 L. 104:105 L. 104:105 L. 104:105 N-linked glycoproteome profiling of seedling leaf in Brachypodium distachyon L. Brachypodium distachyon L., a model plant for cereal crops, has become important as an alternative and potential biofuel grass. 25652041 0 14 theme biofuel 193:199 arg1 grass 201:205 potential biofuel grass 183:205 potential biofuel grass 183:205 N-linked glycoproteome profiling of seedling leaf in Brachypodium distachyon L. Brachypodium distachyon L., a model plant for cereal crops, has become important as an alternative and potential biofuel grass. 25652041 1 15 theme tissues 424:430 arg1 stability 375:383 stability 375:383 stability of protein structure 375:404 In plants, N-glycosylation is one of the most common and important protein modifications, playing important roles in signal recognition, increase in protein activity, stability of protein structure, and formation of tissues and organs. 25652041 1 15 theme tissues 424:430 arg1 increase 345:352 increase 345:352 increase in protein activity 345:372 In plants, N-glycosylation is one of the most common and important protein modifications, playing important roles in signal recognition, increase in protein activity, stability of protein structure, and formation of tissues and organs. 25652041 1 15 theme tissues 424:430 arg1 formation 411:419 formation 411:419 formation of tissues and organs 411:441 In plants, N-glycosylation is one of the most common and important protein modifications, playing important roles in signal recognition, increase in protein activity, stability of protein structure, and formation of tissues and organs. 25652041 1 15 theme tissues 424:430 arg1 recognition 332:342 signal recognition 325:342 signal recognition 325:342 In plants, N-glycosylation is one of the most common and important protein modifications, playing important roles in signal recognition, increase in protein activity, stability of protein structure, and formation of tissues and organs. 25652041 5 16 dep modification 1000:1011 arg1 the 996:998 the 996:998 the 996:998 Further functional analysis suggested that some of these identified glycoproteins are involved in signal transduction, protein trafficking, and quality control and the modification and remodeling of cell-wall components such as receptor-like kinases, protein disulfide isomerase, and polygalacturonase. 25652041 5 17 theme Further 832:838 arg1 analysis 851:858 Further functional analysis 832:858 Further functional analysis 832:858 Further functional analysis suggested that some of these identified glycoproteins are involved in signal transduction, protein trafficking, and quality control and the modification and remodeling of cell-wall components such as receptor-like kinases, protein disulfide isomerase, and polygalacturonase. 25652041 2 18 dep the 508:510 arg1 leaves 521:526 leaves 521:526 leaves 521:526 In this study, we performed the first glycoproteome analysis in the seedling leaves of B. distachyon. 25652041 0 19 from leaf 45:48 arg1 plant 116:120 a model plant 108:120 a model plant for cereal crops 108:137 N-linked glycoproteome profiling of seedling leaf in Brachypodium distachyon L. Brachypodium distachyon L., a model plant for cereal crops, has become important as an alternative and potential biofuel grass. 25652041 0 19 from leaf 45:48 arg1 L. 104:105 L. 104:105 L. 104:105 N-linked glycoproteome profiling of seedling leaf in Brachypodium distachyon L. Brachypodium distachyon L., a model plant for cereal crops, has become important as an alternative and potential biofuel grass. 25652041 0 20 theme potential 183:191 arg1 grass 201:205 potential biofuel grass 183:205 potential biofuel grass 183:205 N-linked glycoproteome profiling of seedling leaf in Brachypodium distachyon L. Brachypodium distachyon L., a model plant for cereal crops, has become important as an alternative and potential biofuel grass. 25652041 6 21 theme peptide 1178:1184 arg1 prediction 1186:1195 signal peptide prediction 1171:1195 signal peptide prediction 1171:1195 Moreover, transmembrane helices and signal peptide prediction showed that most of these glycoproteins could participate in typical protein secretory pathways in eukaryotes. 25652041 5 22 theme functional 840:849 arg1 analysis 851:858 Further functional analysis 832:858 Further functional analysis 832:858 Further functional analysis suggested that some of these identified glycoproteins are involved in signal transduction, protein trafficking, and quality control and the modification and remodeling of cell-wall components such as receptor-like kinases, protein disulfide isomerase, and polygalacturonase. 25652041 0 23 theme glycoproteome 9:21 arg1 profiling 23:31 N-linked glycoproteome profiling 0:31 N-linked glycoproteome profiling of seedling leaf in Brachypodium distachyon L. Brachypodium distachyon L., a model plant for cereal crops, 0:138 N-linked glycoproteome profiling of seedling leaf in Brachypodium distachyon L. Brachypodium distachyon L., a model plant for cereal crops, has become important as an alternative and potential biofuel grass. 25652041 6 24 theme signal 1171:1176 arg1 prediction 1186:1195 signal peptide prediction 1171:1195 signal peptide prediction 1171:1195 Moreover, transmembrane helices and signal peptide prediction showed that most of these glycoproteins could participate in typical protein secretory pathways in eukaryotes. 25652041 6 25 gly glycoproteins 1223:1235 arg1 glycoproteins 1223:1235 these glycoproteins 1217:1235 these glycoproteins 1217:1235 Moreover, transmembrane helices and signal peptide prediction showed that most of these glycoproteins could participate in typical protein secretory pathways in eukaryotes. 25652041 1 26 theme organs 436:441 arg1 stability 375:383 stability 375:383 stability of protein structure 375:404 In plants, N-glycosylation is one of the most common and important protein modifications, playing important roles in signal recognition, increase in protein activity, stability of protein structure, and formation of tissues and organs. 25652041 1 26 theme organs 436:441 arg1 increase 345:352 increase 345:352 increase in protein activity 345:372 In plants, N-glycosylation is one of the most common and important protein modifications, playing important roles in signal recognition, increase in protein activity, stability of protein structure, and formation of tissues and organs. 25652041 1 26 theme organs 436:441 arg1 formation 411:419 formation 411:419 formation of tissues and organs 411:441 In plants, N-glycosylation is one of the most common and important protein modifications, playing important roles in signal recognition, increase in protein activity, stability of protein structure, and formation of tissues and organs. 25652041 1 26 theme organs 436:441 arg1 recognition 332:342 signal recognition 325:342 signal recognition 325:342 In plants, N-glycosylation is one of the most common and important protein modifications, playing important roles in signal recognition, increase in protein activity, stability of protein structure, and formation of tissues and organs. 25652041 4 27 theme conserved 742:750 arg1 motifs 752:757 two conserved motifs 738:757 two conserved motifs 738:757 Motif-X analysis showed that two conserved motifs, N-X-T/S (X is any amino acid, except Pro), were significantly enriched. 25652041 4 27 theme conserved 742:750 arg1 N-X-T/S 760:766 N-X-T/S 760:766 N-X-T/S (X is any amino acid, except Pro) 760:800 Motif-X analysis showed that two conserved motifs, N-X-T/S (X is any amino acid, except Pro), were significantly enriched. 25652041 7 28 from growth 1405:1410 arg1 distachyon 1437:1446 B. distachyon 1434:1446 B. distachyon 1434:1446 The results provide a general overview of protein N-glycosylation modifications during the early growth of seedling leaves in B. distachyon and supplement the glycoproteome databases of plants. 25652041 3 29 theme N-linked 685:692 arg1 glycoproteins 694:706 46 N-linked glycoproteins 682:706 46 N-linked glycoproteins 682:706 Using lectin affinity chromatography enrichment and mass-spectrometry-based analysis, we identified 47 glycosylation sites representing 46 N-linked glycoproteins. 25652041 0 30 theme N-linked 0:7 arg1 profiling 23:31 N-linked glycoproteome profiling 0:31 N-linked glycoproteome profiling of seedling leaf in Brachypodium distachyon L. Brachypodium distachyon L., a model plant for cereal crops, 0:138 N-linked glycoproteome profiling of seedling leaf in Brachypodium distachyon L. Brachypodium distachyon L., a model plant for cereal crops, has become important as an alternative and potential biofuel grass. 25652041 3 31 theme glycosylation 649:661 arg1 sites 663:667 47 glycosylation sites 646:667 47 glycosylation sites representing 46 N-linked glycoproteins 646:706 Using lectin affinity chromatography enrichment and mass-spectrometry-based analysis, we identified 47 glycosylation sites representing 46 N-linked glycoproteins. 25652041 5 32 theme signal 930:935 arg1 transduction 937:948 signal transduction 930:948 signal transduction 930:948 Further functional analysis suggested that some of these identified glycoproteins are involved in signal transduction, protein trafficking, and quality control and the modification and remodeling of cell-wall components such as receptor-like kinases, protein disulfide isomerase, and polygalacturonase. 25652041 7 33 theme protein 1350:1356 arg1 modifications 1374:1386 protein N-glycosylation modifications 1350:1386 protein N-glycosylation modifications 1350:1386 The results provide a general overview of protein N-glycosylation modifications during the early growth of seedling leaves in B. distachyon and supplement the glycoproteome databases of plants. 25652041 1 34 from recognition 332:342 arg1 activity 365:372 protein activity 357:372 protein activity 357:372 In plants, N-glycosylation is one of the most common and important protein modifications, playing important roles in signal recognition, increase in protein activity, stability of protein structure, and formation of tissues and organs. 25652041 1 35 theme common 254:259 arg1 modifications 283:295 the most common and important protein modifications 245:295 the most common and important protein modifications 245:295 In plants, N-glycosylation is one of the most common and important protein modifications, playing important roles in signal recognition, increase in protein activity, stability of protein structure, and formation of tissues and organs. 25652041 5 36 gly glycoproteins 900:912 arg1 glycoproteins 900:912 these identified glycoproteins 883:912 these identified glycoproteins 883:912 Further functional analysis suggested that some of these identified glycoproteins are involved in signal transduction, protein trafficking, and quality control and the modification and remodeling of cell-wall components such as receptor-like kinases, protein disulfide isomerase, and polygalacturonase. 25652041 0 37 link N-linked 0:7 arg1 profiling 23:31 N-linked glycoproteome profiling 0:31 N-linked glycoproteome profiling of seedling leaf in Brachypodium distachyon L. Brachypodium distachyon L., a model plant for cereal crops, 0:138 N-linked glycoproteome profiling of seedling leaf in Brachypodium distachyon L. Brachypodium distachyon L., a model plant for cereal crops, has become important as an alternative and potential biofuel grass. 25652041 7 38 theme B. 1434:1435 arg1 distachyon 1437:1446 B. distachyon 1434:1446 B. distachyon 1434:1446 The results provide a general overview of protein N-glycosylation modifications during the early growth of seedling leaves in B. distachyon and supplement the glycoproteome databases of plants. 25652041 3 39 link N-linked 685:692 arg1 glycoproteins 694:706 46 N-linked glycoproteins 682:706 46 N-linked glycoproteins 682:706 Using lectin affinity chromatography enrichment and mass-spectrometry-based analysis, we identified 47 glycosylation sites representing 46 N-linked glycoproteins. 25652041 3 40 dep chromatography 568:581 arg1 enrichment 583:592 enrichment 583:592 enrichment 583:592 Using lectin affinity chromatography enrichment and mass-spectrometry-based analysis, we identified 47 glycosylation sites representing 46 N-linked glycoproteins. 25652041 1 41 theme protein 357:363 arg1 activity 365:372 protein activity 357:372 protein activity 357:372 In plants, N-glycosylation is one of the most common and important protein modifications, playing important roles in signal recognition, increase in protein activity, stability of protein structure, and formation of tissues and organs. 25652041 4 42 dep N-X-T/S 760:766 arg1 acid 784:787 any amino acid 774:787 any amino acid 774:787 Motif-X analysis showed that two conserved motifs, N-X-T/S (X is any amino acid, except Pro), were significantly enriched. 25652041 0 43 theme leaf 45:48 arg1 profiling 23:31 N-linked glycoproteome profiling 0:31 N-linked glycoproteome profiling of seedling leaf in Brachypodium distachyon L. Brachypodium distachyon L., a model plant for cereal crops, 0:138 N-linked glycoproteome profiling of seedling leaf in Brachypodium distachyon L. Brachypodium distachyon L., a model plant for cereal crops, has become important as an alternative and potential biofuel grass. 25652041 1 44 theme important 265:273 arg1 modifications 283:295 the most common and important protein modifications 245:295 the most common and important protein modifications 245:295 In plants, N-glycosylation is one of the most common and important protein modifications, playing important roles in signal recognition, increase in protein activity, stability of protein structure, and formation of tissues and organs. 25652041 3 45 theme lectin 552:557 arg1 chromatography 568:581 lectin affinity chromatography enrichment and mass-spectrometry-based analysis 552:629 chromatography 568:581 Using lectin affinity chromatography enrichment and mass-spectrometry-based analysis, we identified 47 glycosylation sites representing 46 N-linked glycoproteins. 25652041 0 46 theme seedling 36:43 arg1 leaf 45:48 seedling leaf 36:48 seedling leaf in Brachypodium distachyon L. Brachypodium distachyon L., a model plant for cereal crops, 36:138 N-linked glycoproteome profiling of seedling leaf in Brachypodium distachyon L. Brachypodium distachyon L., a model plant for cereal crops, has become important as an alternative and potential biofuel grass. 25652041 1 47 theme protein 275:281 arg1 modifications 283:295 the most common and important protein modifications 245:295 the most common and important protein modifications 245:295 In plants, N-glycosylation is one of the most common and important protein modifications, playing important roles in signal recognition, increase in protein activity, stability of protein structure, and formation of tissues and organs. 25652041 0 48 theme cereal 126:131 arg1 crops 133:137 cereal crops 126:137 cereal crops 126:137 N-linked glycoproteome profiling of seedling leaf in Brachypodium distachyon L. Brachypodium distachyon L., a model plant for cereal crops, has become important as an alternative and potential biofuel grass. 25652041 7 49 theme N-glycosylation 1358:1372 arg1 modifications 1374:1386 protein N-glycosylation modifications 1350:1386 protein N-glycosylation modifications 1350:1386 The results provide a general overview of protein N-glycosylation modifications during the early growth of seedling leaves in B. distachyon and supplement the glycoproteome databases of plants. 25652041 3 50 theme affinity 559:566 arg1 chromatography 568:581 lectin affinity chromatography enrichment and mass-spectrometry-based analysis 552:629 chromatography 568:581 Using lectin affinity chromatography enrichment and mass-spectrometry-based analysis, we identified 47 glycosylation sites representing 46 N-linked glycoproteins. 25652041 7 51 theme seedling 1415:1422 arg1 growth 1405:1410 the early growth 1395:1410 the early growth of seedling leaves in B. distachyon 1395:1446 The results provide a general overview of protein N-glycosylation modifications during the early growth of seedling leaves in B. distachyon and supplement the glycoproteome databases of plants. 25652041 1 52 theme modifications 283:295 arg1 one 238:240 one 238:240 one 238:240 In plants, N-glycosylation is one of the most common and important protein modifications, playing important roles in signal recognition, increase in protein activity, stability of protein structure, and formation of tissues and organs. 25652041 1 52 theme modifications 283:295 arg1 modifications 283:295 the most common and important protein modifications 245:295 the most common and important protein modifications 245:295 In plants, N-glycosylation is one of the most common and important protein modifications, playing important roles in signal recognition, increase in protein activity, stability of protein structure, and formation of tissues and organs. 25652041 7 53 theme early 1399:1403 arg1 growth 1405:1410 the early growth 1395:1410 the early growth of seedling leaves in B. distachyon 1395:1446 The results provide a general overview of protein N-glycosylation modifications during the early growth of seedling leaves in B. distachyon and supplement the glycoproteome databases of plants. 25652041 5 54 theme protein 1083:1089 arg1 isomerase 1101:1109 protein disulfide isomerase 1083:1109 protein disulfide isomerase 1083:1109 Further functional analysis suggested that some of these identified glycoproteins are involved in signal transduction, protein trafficking, and quality control and the modification and remodeling of cell-wall components such as receptor-like kinases, protein disulfide isomerase, and polygalacturonase. 25652041 7 55 theme plants 1494:1499 arg1 databases 1481:1489 the glycoproteome databases 1463:1489 the glycoproteome databases of plants 1463:1499 The results provide a general overview of protein N-glycosylation modifications during the early growth of seedling leaves in B. distachyon and supplement the glycoproteome databases of plants. 25652041 5 56 theme identified 889:898 arg1 glycoproteins 900:912 these identified glycoproteins 883:912 these identified glycoproteins 883:912 Further functional analysis suggested that some of these identified glycoproteins are involved in signal transduction, protein trafficking, and quality control and the modification and remodeling of cell-wall components such as receptor-like kinases, protein disulfide isomerase, and polygalacturonase. 25652041 1 57 from one 238:240 arg1 plants 211:216 plants 211:216 plants 211:216 In plants, N-glycosylation is one of the most common and important protein modifications, playing important roles in signal recognition, increase in protein activity, stability of protein structure, and formation of tissues and organs. 25652041 2 58 theme B. 531:532 arg1 distachyon 534:543 B. distachyon 531:543 B. distachyon 531:543 In this study, we performed the first glycoproteome analysis in the seedling leaves of B. distachyon. 25652041 5 59 theme cell-wall 1031:1039 arg1 kinases 1074:1080 receptor-like kinases 1060:1080 receptor-like kinases 1060:1080 Further functional analysis suggested that some of these identified glycoproteins are involved in signal transduction, protein trafficking, and quality control and the modification and remodeling of cell-wall components such as receptor-like kinases, protein disulfide isomerase, and polygalacturonase. 25652041 5 59 theme cell-wall 1031:1039 arg1 components 1041:1050 cell-wall components 1031:1050 cell-wall components such as receptor-like kinases, protein disulfide isomerase, and polygalacturonase 1031:1132 Further functional analysis suggested that some of these identified glycoproteins are involved in signal transduction, protein trafficking, and quality control and the modification and remodeling of cell-wall components such as receptor-like kinases, protein disulfide isomerase, and polygalacturonase. 25652041 5 59 theme cell-wall 1031:1039 arg1 polygalacturonase 1116:1132 polygalacturonase 1116:1132 polygalacturonase 1116:1132 Further functional analysis suggested that some of these identified glycoproteins are involved in signal transduction, protein trafficking, and quality control and the modification and remodeling of cell-wall components such as receptor-like kinases, protein disulfide isomerase, and polygalacturonase. 25652041 5 59 theme cell-wall 1031:1039 arg1 isomerase 1101:1109 protein disulfide isomerase 1083:1109 protein disulfide isomerase 1083:1109 Further functional analysis suggested that some of these identified glycoproteins are involved in signal transduction, protein trafficking, and quality control and the modification and remodeling of cell-wall components such as receptor-like kinases, protein disulfide isomerase, and polygalacturonase. 25652041 5 60 theme components 1041:1050 arg1 transduction 937:948 signal transduction 930:948 signal transduction 930:948 Further functional analysis suggested that some of these identified glycoproteins are involved in signal transduction, protein trafficking, and quality control and the modification and remodeling of cell-wall components such as receptor-like kinases, protein disulfide isomerase, and polygalacturonase. 25652041 5 60 theme components 1041:1050 arg1 trafficking 959:969 protein trafficking 951:969 protein trafficking 951:969 Further functional analysis suggested that some of these identified glycoproteins are involved in signal transduction, protein trafficking, and quality control and the modification and remodeling of cell-wall components such as receptor-like kinases, protein disulfide isomerase, and polygalacturonase. 25652041 5 60 theme components 1041:1050 arg1 remodeling 1017:1026 remodeling 1017:1026 remodeling 1017:1026 Further functional analysis suggested that some of these identified glycoproteins are involved in signal transduction, protein trafficking, and quality control and the modification and remodeling of cell-wall components such as receptor-like kinases, protein disulfide isomerase, and polygalacturonase. 25652041 5 60 theme components 1041:1050 arg1 control 984:990 quality control 976:990 quality control 976:990 Further functional analysis suggested that some of these identified glycoproteins are involved in signal transduction, protein trafficking, and quality control and the modification and remodeling of cell-wall components such as receptor-like kinases, protein disulfide isomerase, and polygalacturonase. 25652041 5 60 theme components 1041:1050 arg1 modification 1000:1011 modification 1000:1011 modification 1000:1011 Further functional analysis suggested that some of these identified glycoproteins are involved in signal transduction, protein trafficking, and quality control and the modification and remodeling of cell-wall components such as receptor-like kinases, protein disulfide isomerase, and polygalacturonase. 25652041 4 61 theme Motif-X 709:715 arg1 analysis 717:724 Motif-X analysis 709:724 Motif-X analysis 709:724 Motif-X analysis showed that two conserved motifs, N-X-T/S (X is any amino acid, except Pro), were significantly enriched. 25652041 1 62 theme protein 388:394 arg1 structure 396:404 protein structure 388:404 protein structure 388:404 In plants, N-glycosylation is one of the most common and important protein modifications, playing important roles in signal recognition, increase in protein activity, stability of protein structure, and formation of tissues and organs. 25652041 4 63 theme amino 778:782 arg1 acid 784:787 any amino acid 774:787 any amino acid 774:787 Motif-X analysis showed that two conserved motifs, N-X-T/S (X is any amino acid, except Pro), were significantly enriched. 25652041 7 64 from distachyon 1437:1446 arg1 seedling 1415:1422 seedling 1415:1422 seedling 1415:1422 The results provide a general overview of protein N-glycosylation modifications during the early growth of seedling leaves in B. distachyon and supplement the glycoproteome databases of plants. 25652041 7 64 from distachyon 1437:1446 arg1 growth 1405:1410 the early growth 1395:1410 the early growth of seedling leaves in B. distachyon 1395:1446 The results provide a general overview of protein N-glycosylation modifications during the early growth of seedling leaves in B. distachyon and supplement the glycoproteome databases of plants. 25652041 7 65 theme glycoproteome 1467:1479 arg1 databases 1481:1489 the glycoproteome databases 1463:1489 the glycoproteome databases of plants 1463:1499 The results provide a general overview of protein N-glycosylation modifications during the early growth of seedling leaves in B. distachyon and supplement the glycoproteome databases of plants. 25652041 1 66 theme structure 396:404 arg1 stability 375:383 stability 375:383 stability of protein structure 375:404 In plants, N-glycosylation is one of the most common and important protein modifications, playing important roles in signal recognition, increase in protein activity, stability of protein structure, and formation of tissues and organs. 25652041 1 66 theme structure 396:404 arg1 increase 345:352 increase 345:352 increase in protein activity 345:372 In plants, N-glycosylation is one of the most common and important protein modifications, playing important roles in signal recognition, increase in protein activity, stability of protein structure, and formation of tissues and organs. 25652041 1 66 theme structure 396:404 arg1 formation 411:419 formation 411:419 formation of tissues and organs 411:441 In plants, N-glycosylation is one of the most common and important protein modifications, playing important roles in signal recognition, increase in protein activity, stability of protein structure, and formation of tissues and organs. 25652041 1 66 theme structure 396:404 arg1 recognition 332:342 signal recognition 325:342 signal recognition 325:342 In plants, N-glycosylation is one of the most common and important protein modifications, playing important roles in signal recognition, increase in protein activity, stability of protein structure, and formation of tissues and organs. 25652041 3 67 theme mass-spectrometry-based 598:620 arg1 analysis 622:629 mass-spectrometry-based analysis 598:629 mass-spectrometry-based analysis 598:629 Using lectin affinity chromatography enrichment and mass-spectrometry-based analysis, we identified 47 glycosylation sites representing 46 N-linked glycoproteins. 25652041 7 68 from seedling 1415:1422 arg1 distachyon 1437:1446 B. distachyon 1434:1446 B. distachyon 1434:1446 The results provide a general overview of protein N-glycosylation modifications during the early growth of seedling leaves in B. distachyon and supplement the glycoproteome databases of plants. 25652041 2 69 from analysis 496:503 arg1 the 508:510 the 508:510 the 508:510 In this study, we performed the first glycoproteome analysis in the seedling leaves of B. distachyon. 25652041 0 70 from L. 104:105 arg1 profiling 23:31 N-linked glycoproteome profiling 0:31 N-linked glycoproteome profiling of seedling leaf in Brachypodium distachyon L. Brachypodium distachyon L., a model plant for cereal crops, 0:138 N-linked glycoproteome profiling of seedling leaf in Brachypodium distachyon L. Brachypodium distachyon L., a model plant for cereal crops, has become important as an alternative and potential biofuel grass. 25652041 3 71 gly glycoproteins 694:706 arg1 glycoproteins 694:706 46 N-linked glycoproteins 682:706 46 N-linked glycoproteins 682:706 Using lectin affinity chromatography enrichment and mass-spectrometry-based analysis, we identified 47 glycosylation sites representing 46 N-linked glycoproteins. 25652041 7 72 theme modifications 1374:1386 arg1 overview 1338:1345 a general overview 1328:1345 a general overview of protein N-glycosylation modifications during the early growth of seedling leaves in B. distachyon 1328:1446 The results provide a general overview of protein N-glycosylation modifications during the early growth of seedling leaves in B. distachyon and supplement the glycoproteome databases of plants. 25652041 3 73 gly glycosylation 649:661 arg2 sites 663:667 47 glycosylation sites 646:667 47 glycosylation sites representing 46 N-linked glycoproteins 646:706 Using lectin affinity chromatography enrichment and mass-spectrometry-based analysis, we identified 47 glycosylation sites representing 46 N-linked glycoproteins. 25652041 3 73 gly glycosylation 649:661 arg2 47 646:647 47 646:647 47 646:647 Using lectin affinity chromatography enrichment and mass-spectrometry-based analysis, we identified 47 glycosylation sites representing 46 N-linked glycoproteins. 25652041 5 74 theme quality 976:982 arg1 control 984:990 quality control 976:990 quality control 976:990 Further functional analysis suggested that some of these identified glycoproteins are involved in signal transduction, protein trafficking, and quality control and the modification and remodeling of cell-wall components such as receptor-like kinases, protein disulfide isomerase, and polygalacturonase. 25652041 1 75 theme important 306:314 arg1 roles 316:320 important roles 306:320 important roles 306:320 In plants, N-glycosylation is one of the most common and important protein modifications, playing important roles in signal recognition, increase in protein activity, stability of protein structure, and formation of tissues and organs. 25652041 6 76 theme protein 1266:1272 arg1 pathways 1284:1291 typical protein secretory pathways 1258:1291 typical protein secretory pathways 1258:1291 Moreover, transmembrane helices and signal peptide prediction showed that most of these glycoproteins could participate in typical protein secretory pathways in eukaryotes. 25652041 1 77 from increase 345:352 arg1 activity 365:372 protein activity 357:372 protein activity 357:372 In plants, N-glycosylation is one of the most common and important protein modifications, playing important roles in signal recognition, increase in protein activity, stability of protein structure, and formation of tissues and organs. 25652041 2 78 theme first 476:480 arg1 analysis 496:503 the first glycoproteome analysis 472:503 the first glycoproteome analysis in the seedling leaves of B. distachyon 472:543 In this study, we performed the first glycoproteome analysis in the seedling leaves of B. distachyon. 28348838 0 0 theme strong 85:90 arg1 association 97:107 strong host association 85:107 strong host association 85:107 Sequence-based analysis of the genus Ruminococcus resolves its phylogeny and reveals strong host association. 28348838 5 1 theme other 674:678 arg1 ruminants 680:688 other ruminants 674:688 other ruminants 674:688 Originally isolated from the bovine rumen, ruminococci have been found in numerous mammalian hosts, including other ruminants, and non-ruminants such as horses, pigs and humans. 28348838 9 2 located found 1626:1630 arg2 ruminococci 1610:1620 very few ruminococci 1601:1620 very few ruminococci 1601:1620 We present evidence that ruminococci are predominantly associated with herbivores and omnivores, and our data supports the hypothesis that very few ruminococci are found consistently in non-host-associated environments. 28348838 9 2 located found 1626:1630 arg1 environments 1668:1679 non-host-associated environments 1648:1679 non-host-associated environments 1648:1679 We present evidence that ruminococci are predominantly associated with herbivores and omnivores, and our data supports the hypothesis that very few ruminococci are found consistently in non-host-associated environments. 28348838 10 3 from distribution 1810:1821 arg1 systems 1834:1840 natural systems 1826:1840 natural systems 1826:1840 This study not only helps to resolve the phylogeny of this important genus, but also provides a framework for understanding its distribution in natural systems. 28348838 8 4 theme studies 1254:1260 arg1 wealth 1165:1170 the wealth 1161:1170 the wealth of publicly available 16S rRNA gene sequences, genomes and large-scale microbiota studies 1161:1260 Here, we capitalized on the wealth of publicly available 16S rRNA gene sequences, genomes and large-scale microbiota studies to both resolve the phylogenetic placement of described species in the genus Ruminococcus, and further demonstrate that this genus has largely unexplored diversity and a staggering host distribution. 28348838 3 5 theme gut 364:366 arg1 microbes 368:375 many gut microbes 359:375 many gut microbes 359:375 For example, many gut microbes are involved in the conversion of host-ingested dietary polysaccharides into host-usable nutrients. 28348838 4 6 from bacteria 528:535 arg1 Ruminococcus 550:561 the genus Ruminococcus 540:561 the genus Ruminococcus 540:561 One group of important gut microbial symbionts are bacteria in the genus Ruminococcus. 28348838 7 7 theme Most 893:896 arg1 ruminococci 898:908 Most ruminococci 893:908 Most ruminococci that have been studied 893:931 Most ruminococci that have been studied are those capable of degrading cellulose, much less is known about non-cellulolytic non-ruminant-associated species, and even less is known about the environmental distribution of ruminococci as a whole. 28348838 0 8 theme host 92:95 arg1 association 97:107 strong host association 85:107 strong host association 85:107 Sequence-based analysis of the genus Ruminococcus resolves its phylogeny and reveals strong host association. 28348838 4 9 theme gut 500:502 arg1 symbionts 514:522 important gut microbial symbionts 490:522 important gut microbial symbionts 490:522 One group of important gut microbial symbionts are bacteria in the genus Ruminococcus. 28348838 8 10 theme available 1184:1192 arg1 sequences 1208:1216 publicly available 16S rRNA gene sequences 1175:1216 publicly available 16S rRNA gene sequences 1175:1216 Here, we capitalized on the wealth of publicly available 16S rRNA gene sequences, genomes and large-scale microbiota studies to both resolve the phylogenetic placement of described species in the genus Ruminococcus, and further demonstrate that this genus has largely unexplored diversity and a staggering host distribution. 28348838 4 11 theme important 490:498 arg1 symbionts 514:522 important gut microbial symbionts 490:522 important gut microbial symbionts 490:522 One group of important gut microbial symbionts are bacteria in the genus Ruminococcus. 28348838 5 12 theme mammalian 647:655 arg1 humans 734:739 humans 734:739 humans 734:739 Originally isolated from the bovine rumen, ruminococci have been found in numerous mammalian hosts, including other ruminants, and non-ruminants such as horses, pigs and humans. 28348838 5 12 theme mammalian 647:655 arg1 ruminants 680:688 other ruminants 674:688 other ruminants 674:688 Originally isolated from the bovine rumen, ruminococci have been found in numerous mammalian hosts, including other ruminants, and non-ruminants such as horses, pigs and humans. 28348838 5 12 theme mammalian 647:655 arg1 horses 717:722 horses 717:722 horses 717:722 Originally isolated from the bovine rumen, ruminococci have been found in numerous mammalian hosts, including other ruminants, and non-ruminants such as horses, pigs and humans. 28348838 5 12 theme mammalian 647:655 arg1 hosts 657:661 numerous mammalian hosts 638:661 numerous mammalian hosts 638:661 Originally isolated from the bovine rumen, ruminococci have been found in numerous mammalian hosts, including other ruminants, and non-ruminants such as horses, pigs and humans. 28348838 5 12 theme mammalian 647:655 arg1 pigs 725:728 pigs 725:728 pigs 725:728 Originally isolated from the bovine rumen, ruminococci have been found in numerous mammalian hosts, including other ruminants, and non-ruminants such as horses, pigs and humans. 28348838 5 13 theme numerous 638:645 arg1 humans 734:739 humans 734:739 humans 734:739 Originally isolated from the bovine rumen, ruminococci have been found in numerous mammalian hosts, including other ruminants, and non-ruminants such as horses, pigs and humans. 28348838 5 13 theme numerous 638:645 arg1 ruminants 680:688 other ruminants 674:688 other ruminants 674:688 Originally isolated from the bovine rumen, ruminococci have been found in numerous mammalian hosts, including other ruminants, and non-ruminants such as horses, pigs and humans. 28348838 5 13 theme numerous 638:645 arg1 horses 717:722 horses 717:722 horses 717:722 Originally isolated from the bovine rumen, ruminococci have been found in numerous mammalian hosts, including other ruminants, and non-ruminants such as horses, pigs and humans. 28348838 5 13 theme numerous 638:645 arg1 hosts 657:661 numerous mammalian hosts 638:661 numerous mammalian hosts 638:661 Originally isolated from the bovine rumen, ruminococci have been found in numerous mammalian hosts, including other ruminants, and non-ruminants such as horses, pigs and humans. 28348838 5 13 theme numerous 638:645 arg1 pigs 725:728 pigs 725:728 pigs 725:728 Originally isolated from the bovine rumen, ruminococci have been found in numerous mammalian hosts, including other ruminants, and non-ruminants such as horses, pigs and humans. 28348838 1 14 theme microbial 181:189 arg1 communities 191:201 mammalian gut microbial communities 167:201 mammalian gut microbial communities 167:201 It has become increasingly clear that the composition of mammalian gut microbial communities is substantially diet driven. 28348838 1 15 theme mammalian 167:175 arg1 communities 191:201 mammalian gut microbial communities 167:201 mammalian gut microbial communities 167:201 It has become increasingly clear that the composition of mammalian gut microbial communities is substantially diet driven. 28348838 3 16 theme many 359:362 arg1 microbes 368:375 many gut microbes 359:375 many gut microbes 359:375 For example, many gut microbes are involved in the conversion of host-ingested dietary polysaccharides into host-usable nutrients. 28348838 4 17 theme symbionts 514:522 arg1 bacteria 528:535 bacteria 528:535 bacteria in the genus Ruminococcus 528:561 One group of important gut microbial symbionts are bacteria in the genus Ruminococcus. 28348838 4 17 theme symbionts 514:522 arg1 symbionts 514:522 important gut microbial symbionts 490:522 important gut microbial symbionts 490:522 One group of important gut microbial symbionts are bacteria in the genus Ruminococcus. 28348838 4 17 theme symbionts 514:522 arg1 group 481:485 One group 477:485 One group of important gut microbial symbionts 477:522 One group of important gut microbial symbionts are bacteria in the genus Ruminococcus. 28348838 0 18 theme Ruminococcus 37:48 arg1 analysis 15:22 Sequence-based analysis 0:22 Sequence-based analysis of the genus Ruminococcus 0:48 Sequence-based analysis of the genus Ruminococcus resolves its phylogeny and reveals strong host association. 28348838 6 19 theme substrate 814:822 arg1 preferences 824:834 their substrate preferences 808:834 their substrate preferences 808:834 All ruminococci require fermentable carbohydrates for growth, and their substrate preferences appear to be based on the diet of their particular host. 28348838 8 20 theme 16S 1194:1196 arg1 sequences 1208:1216 publicly available 16S rRNA gene sequences 1175:1216 publicly available 16S rRNA gene sequences 1175:1216 Here, we capitalized on the wealth of publicly available 16S rRNA gene sequences, genomes and large-scale microbiota studies to both resolve the phylogenetic placement of described species in the genus Ruminococcus, and further demonstrate that this genus has largely unexplored diversity and a staggering host distribution. 28348838 1 21 theme gut 177:179 arg1 communities 191:201 mammalian gut microbial communities 167:201 mammalian gut microbial communities 167:201 It has become increasingly clear that the composition of mammalian gut microbial communities is substantially diet driven. 28348838 5 22 located found 629:633 arg1 pigs 725:728 pigs 725:728 pigs 725:728 Originally isolated from the bovine rumen, ruminococci have been found in numerous mammalian hosts, including other ruminants, and non-ruminants such as horses, pigs and humans. 28348838 5 22 located found 629:633 arg1 hosts 657:661 numerous mammalian hosts 638:661 numerous mammalian hosts 638:661 Originally isolated from the bovine rumen, ruminococci have been found in numerous mammalian hosts, including other ruminants, and non-ruminants such as horses, pigs and humans. 28348838 5 22 located found 629:633 arg1 humans 734:739 humans 734:739 humans 734:739 Originally isolated from the bovine rumen, ruminococci have been found in numerous mammalian hosts, including other ruminants, and non-ruminants such as horses, pigs and humans. 28348838 5 22 located found 629:633 arg1 non-ruminants 695:707 non-ruminants 695:707 non-ruminants such as horses, pigs and humans 695:739 Originally isolated from the bovine rumen, ruminococci have been found in numerous mammalian hosts, including other ruminants, and non-ruminants such as horses, pigs and humans. 28348838 5 22 located found 629:633 arg1 horses 717:722 horses 717:722 horses 717:722 Originally isolated from the bovine rumen, ruminococci have been found in numerous mammalian hosts, including other ruminants, and non-ruminants such as horses, pigs and humans. 28348838 5 22 located found 629:633 arg2 ruminococci 607:617 ruminococci 607:617 ruminococci 607:617 Originally isolated from the bovine rumen, ruminococci have been found in numerous mammalian hosts, including other ruminants, and non-ruminants such as horses, pigs and humans. 28348838 5 22 located found 629:633 arg1 ruminants 680:688 other ruminants 674:688 other ruminants 674:688 Originally isolated from the bovine rumen, ruminococci have been found in numerous mammalian hosts, including other ruminants, and non-ruminants such as horses, pigs and humans. 28348838 4 23 theme microbial 504:512 arg1 symbionts 514:522 important gut microbial symbionts 490:522 important gut microbial symbionts 490:522 One group of important gut microbial symbionts are bacteria in the genus Ruminococcus. 28348838 10 24 theme natural 1826:1832 arg1 systems 1834:1840 natural systems 1826:1840 natural systems 1826:1840 This study not only helps to resolve the phylogeny of this important genus, but also provides a framework for understanding its distribution in natural systems. 28348838 2 25 theme overall 330:336 arg1 health 338:343 overall health 330:343 overall health 330:343 These microbiota form intricate mutualisms with their hosts, which have profound implications on overall health. 28348838 3 26 theme polysaccharides 433:447 arg1 conversion 397:406 the conversion 393:406 the conversion of host-ingested dietary polysaccharides into host-usable nutrients 393:474 For example, many gut microbes are involved in the conversion of host-ingested dietary polysaccharides into host-usable nutrients. 28348838 0 27 theme Sequence-based 0:13 arg1 analysis 15:22 Sequence-based analysis 0:22 Sequence-based analysis of the genus Ruminococcus 0:48 Sequence-based analysis of the genus Ruminococcus resolves its phylogeny and reveals strong host association. 28348838 7 28 theme ruminococci 1113:1123 arg1 distribution 1097:1108 the environmental distribution 1079:1108 the environmental distribution of ruminococci 1079:1123 Most ruminococci that have been studied are those capable of degrading cellulose, much less is known about non-cellulolytic non-ruminant-associated species, and even less is known about the environmental distribution of ruminococci as a whole. 28348838 9 29 theme few 1606:1608 arg1 ruminococci 1610:1620 very few ruminococci 1601:1620 very few ruminococci 1601:1620 We present evidence that ruminococci are predominantly associated with herbivores and omnivores, and our data supports the hypothesis that very few ruminococci are found consistently in non-host-associated environments. 28348838 1 30 theme communities 191:201 arg1 composition 152:162 the composition 148:162 the composition of mammalian gut microbial communities 148:201 It has become increasingly clear that the composition of mammalian gut microbial communities is substantially diet driven. 28348838 1 30 theme communities 191:201 arg1 driven 225:230 driven 225:230 driven 225:230 It has become increasingly clear that the composition of mammalian gut microbial communities is substantially diet driven. 28348838 8 31 theme sequences 1208:1216 arg1 wealth 1165:1170 the wealth 1161:1170 the wealth of publicly available 16S rRNA gene sequences, genomes and large-scale microbiota studies 1161:1260 Here, we capitalized on the wealth of publicly available 16S rRNA gene sequences, genomes and large-scale microbiota studies to both resolve the phylogenetic placement of described species in the genus Ruminococcus, and further demonstrate that this genus has largely unexplored diversity and a staggering host distribution. 28348838 7 32 theme environmental 1083:1095 arg1 distribution 1097:1108 the environmental distribution 1079:1108 the environmental distribution of ruminococci 1079:1123 Most ruminococci that have been studied are those capable of degrading cellulose, much less is known about non-cellulolytic non-ruminant-associated species, and even less is known about the environmental distribution of ruminococci as a whole. 28348838 8 33 theme genomes 1219:1225 arg1 wealth 1165:1170 the wealth 1161:1170 the wealth of publicly available 16S rRNA gene sequences, genomes and large-scale microbiota studies 1161:1260 Here, we capitalized on the wealth of publicly available 16S rRNA gene sequences, genomes and large-scale microbiota studies to both resolve the phylogenetic placement of described species in the genus Ruminococcus, and further demonstrate that this genus has largely unexplored diversity and a staggering host distribution. 28348838 8 34 dep resolve 1270:1276 arg1 both 1265:1268 both 1265:1268 both 1265:1268 Here, we capitalized on the wealth of publicly available 16S rRNA gene sequences, genomes and large-scale microbiota studies to both resolve the phylogenetic placement of described species in the genus Ruminococcus, and further demonstrate that this genus has largely unexplored diversity and a staggering host distribution. 28348838 8 35 theme gene 1203:1206 arg1 sequences 1208:1216 publicly available 16S rRNA gene sequences 1175:1216 publicly available 16S rRNA gene sequences 1175:1216 Here, we capitalized on the wealth of publicly available 16S rRNA gene sequences, genomes and large-scale microbiota studies to both resolve the phylogenetic placement of described species in the genus Ruminococcus, and further demonstrate that this genus has largely unexplored diversity and a staggering host distribution. 28348838 6 36 theme host 887:890 arg1 diet 862:865 the diet 858:865 the diet of their particular host 858:890 All ruminococci require fermentable carbohydrates for growth, and their substrate preferences appear to be based on the diet of their particular host. 28348838 2 37 theme profound 305:312 arg1 implications 314:325 profound implications 305:325 profound implications 305:325 These microbiota form intricate mutualisms with their hosts, which have profound implications on overall health. 28348838 3 38 theme host-ingested 411:423 arg1 polysaccharides 433:447 host-ingested dietary polysaccharides 411:447 host-ingested dietary polysaccharides 411:447 For example, many gut microbes are involved in the conversion of host-ingested dietary polysaccharides into host-usable nutrients. 28348838 2 39 contain have 300:303 arg1 mutualisms 265:274 intricate mutualisms 255:274 intricate mutualisms 255:274 These microbiota form intricate mutualisms with their hosts, which have profound implications on overall health. 28348838 2 39 contain have 300:303 arg2 implications 314:325 profound implications 305:325 profound implications 305:325 These microbiota form intricate mutualisms with their hosts, which have profound implications on overall health. 28348838 6 40 theme particular 876:885 arg1 host 887:890 their particular host 870:890 their particular host 870:890 All ruminococci require fermentable carbohydrates for growth, and their substrate preferences appear to be based on the diet of their particular host. 28348838 0 41 theme genus 31:35 arg1 Ruminococcus 37:48 the genus Ruminococcus 27:48 the genus Ruminococcus 27:48 Sequence-based analysis of the genus Ruminococcus resolves its phylogeny and reveals strong host association. 28348838 2 42 with mutualisms 265:274 arg1 hosts 287:291 their hosts 281:291 their hosts 281:291 These microbiota form intricate mutualisms with their hosts, which have profound implications on overall health. 28348838 3 43 theme dietary 425:431 arg1 polysaccharides 433:447 host-ingested dietary polysaccharides 411:447 host-ingested dietary polysaccharides 411:447 For example, many gut microbes are involved in the conversion of host-ingested dietary polysaccharides into host-usable nutrients. 28348838 8 44 theme unexplored 1405:1414 arg1 diversity 1416:1424 largely unexplored diversity 1397:1424 largely unexplored diversity 1397:1424 Here, we capitalized on the wealth of publicly available 16S rRNA gene sequences, genomes and large-scale microbiota studies to both resolve the phylogenetic placement of described species in the genus Ruminococcus, and further demonstrate that this genus has largely unexplored diversity and a staggering host distribution. 28348838 8 45 theme phylogenetic 1282:1293 arg1 placement 1295:1303 the phylogenetic placement 1278:1303 the phylogenetic placement of described species 1278:1324 Here, we capitalized on the wealth of publicly available 16S rRNA gene sequences, genomes and large-scale microbiota studies to both resolve the phylogenetic placement of described species in the genus Ruminococcus, and further demonstrate that this genus has largely unexplored diversity and a staggering host distribution. 28348838 8 46 theme large-scale 1231:1241 arg1 studies 1254:1260 large-scale microbiota studies 1231:1260 large-scale microbiota studies 1231:1260 Here, we capitalized on the wealth of publicly available 16S rRNA gene sequences, genomes and large-scale microbiota studies to both resolve the phylogenetic placement of described species in the genus Ruminococcus, and further demonstrate that this genus has largely unexplored diversity and a staggering host distribution. 28348838 4 47 theme genus 544:548 arg1 Ruminococcus 550:561 the genus Ruminococcus 540:561 the genus Ruminococcus 540:561 One group of important gut microbial symbionts are bacteria in the genus Ruminococcus. 28348838 3 48 theme host-usable 454:464 arg1 nutrients 466:474 host-usable nutrients 454:474 host-usable nutrients 454:474 For example, many gut microbes are involved in the conversion of host-ingested dietary polysaccharides into host-usable nutrients. 28348838 8 49 theme described 1308:1316 arg1 species 1318:1324 described species 1308:1324 described species 1308:1324 Here, we capitalized on the wealth of publicly available 16S rRNA gene sequences, genomes and large-scale microbiota studies to both resolve the phylogenetic placement of described species in the genus Ruminococcus, and further demonstrate that this genus has largely unexplored diversity and a staggering host distribution. 28348838 9 50 theme non-host-associated 1648:1666 arg1 environments 1668:1679 non-host-associated environments 1648:1679 non-host-associated environments 1648:1679 We present evidence that ruminococci are predominantly associated with herbivores and omnivores, and our data supports the hypothesis that very few ruminococci are found consistently in non-host-associated environments. 28348838 7 51 theme non-ruminant-associated 1017:1039 arg1 species 1041:1047 non-cellulolytic non-ruminant-associated species 1000:1047 non-cellulolytic non-ruminant-associated species 1000:1047 Most ruminococci that have been studied are those capable of degrading cellulose, much less is known about non-cellulolytic non-ruminant-associated species, and even less is known about the environmental distribution of ruminococci as a whole. 28348838 10 52 theme genus 1751:1755 arg1 phylogeny 1723:1731 the phylogeny 1719:1731 the phylogeny of this important genus 1719:1755 This study not only helps to resolve the phylogeny of this important genus, but also provides a framework for understanding its distribution in natural systems. 28348838 8 53 theme host 1443:1446 arg1 distribution 1448:1459 a staggering host distribution 1430:1459 a staggering host distribution 1430:1459 Here, we capitalized on the wealth of publicly available 16S rRNA gene sequences, genomes and large-scale microbiota studies to both resolve the phylogenetic placement of described species in the genus Ruminococcus, and further demonstrate that this genus has largely unexplored diversity and a staggering host distribution. 28348838 5 54 theme bovine 593:598 arg1 rumen 600:604 the bovine rumen 589:604 the bovine rumen 589:604 Originally isolated from the bovine rumen, ruminococci have been found in numerous mammalian hosts, including other ruminants, and non-ruminants such as horses, pigs and humans. 28348838 10 55 theme important 1741:1749 arg1 genus 1751:1755 this important genus 1736:1755 this important genus 1736:1755 This study not only helps to resolve the phylogeny of this important genus, but also provides a framework for understanding its distribution in natural systems. 28348838 6 56 theme fermentable 766:776 arg1 carbohydrates 778:790 fermentable carbohydrates 766:790 fermentable carbohydrates for growth 766:801 All ruminococci require fermentable carbohydrates for growth, and their substrate preferences appear to be based on the diet of their particular host. 28348838 8 57 theme staggering 1432:1441 arg1 distribution 1448:1459 a staggering host distribution 1430:1459 a staggering host distribution 1430:1459 Here, we capitalized on the wealth of publicly available 16S rRNA gene sequences, genomes and large-scale microbiota studies to both resolve the phylogenetic placement of described species in the genus Ruminococcus, and further demonstrate that this genus has largely unexplored diversity and a staggering host distribution. 28348838 8 58 theme species 1318:1324 arg1 placement 1295:1303 the phylogenetic placement 1278:1303 the phylogenetic placement of described species 1278:1324 Here, we capitalized on the wealth of publicly available 16S rRNA gene sequences, genomes and large-scale microbiota studies to both resolve the phylogenetic placement of described species in the genus Ruminococcus, and further demonstrate that this genus has largely unexplored diversity and a staggering host distribution. 28348838 8 59 contain has 1393:1395 arg1 genus 1387:1391 this genus 1382:1391 this genus 1382:1391 Here, we capitalized on the wealth of publicly available 16S rRNA gene sequences, genomes and large-scale microbiota studies to both resolve the phylogenetic placement of described species in the genus Ruminococcus, and further demonstrate that this genus has largely unexplored diversity and a staggering host distribution. 28348838 8 59 contain has 1393:1395 arg2 distribution 1448:1459 a staggering host distribution 1430:1459 a staggering host distribution 1430:1459 Here, we capitalized on the wealth of publicly available 16S rRNA gene sequences, genomes and large-scale microbiota studies to both resolve the phylogenetic placement of described species in the genus Ruminococcus, and further demonstrate that this genus has largely unexplored diversity and a staggering host distribution. 28348838 8 59 contain has 1393:1395 arg2 diversity 1416:1424 largely unexplored diversity 1397:1424 largely unexplored diversity 1397:1424 Here, we capitalized on the wealth of publicly available 16S rRNA gene sequences, genomes and large-scale microbiota studies to both resolve the phylogenetic placement of described species in the genus Ruminococcus, and further demonstrate that this genus has largely unexplored diversity and a staggering host distribution. 28348838 7 60 theme non-cellulolytic 1000:1015 arg1 species 1041:1047 non-cellulolytic non-ruminant-associated species 1000:1047 non-cellulolytic non-ruminant-associated species 1000:1047 Most ruminococci that have been studied are those capable of degrading cellulose, much less is known about non-cellulolytic non-ruminant-associated species, and even less is known about the environmental distribution of ruminococci as a whole. 28348838 8 61 theme genus 1333:1337 arg1 Ruminococcus 1339:1350 the genus Ruminococcus 1329:1350 the genus Ruminococcus 1329:1350 Here, we capitalized on the wealth of publicly available 16S rRNA gene sequences, genomes and large-scale microbiota studies to both resolve the phylogenetic placement of described species in the genus Ruminococcus, and further demonstrate that this genus has largely unexplored diversity and a staggering host distribution. 28348838 8 62 theme microbiota 1243:1252 arg1 studies 1254:1260 large-scale microbiota studies 1231:1260 large-scale microbiota studies 1231:1260 Here, we capitalized on the wealth of publicly available 16S rRNA gene sequences, genomes and large-scale microbiota studies to both resolve the phylogenetic placement of described species in the genus Ruminococcus, and further demonstrate that this genus has largely unexplored diversity and a staggering host distribution. 28348838 2 63 theme intricate 255:263 arg1 mutualisms 265:274 intricate mutualisms 255:274 intricate mutualisms 255:274 These microbiota form intricate mutualisms with their hosts, which have profound implications on overall health. 28348838 8 64 theme rRNA 1198:1201 arg1 sequences 1208:1216 publicly available 16S rRNA gene sequences 1175:1216 publicly available 16S rRNA gene sequences 1175:1216 Here, we capitalized on the wealth of publicly available 16S rRNA gene sequences, genomes and large-scale microbiota studies to both resolve the phylogenetic placement of described species in the genus Ruminococcus, and further demonstrate that this genus has largely unexplored diversity and a staggering host distribution. 27665432 2 0 theme TMP 602:604 arg1 of -35 kPa 607:616 a transmembrane pressure (TMP) of -35 kPa 576:616 a transmembrane pressure (TMP) of -35 kPa on Day 433 576:627 The MBRs not only substantially degraded OSPW classical and oxidized NAs, but also demonstrated outstanding membrane fouling control performance (the MBR receiving raw OSPW experienced its first severe fouling with a transmembrane pressure (TMP) of -35 kPa on Day 433). 27665432 3 1 theme O3/L 657:660 arg1 pretreatment 663:674 The mild ozonation (30 mg O3/L) pretreatment 631:674 The mild ozonation (30 mg O3/L) pretreatment of OSPW 631:682 The mild ozonation (30 mg O3/L) pretreatment of OSPW remarkably enhanced OSPW NA degradation, and improved the MBR's fouling control in terms of prolonged long-term slow TMP growth phase and reduced TMP jump frequency. 27665432 4 2 dep growth 966:971 arg1 e.g. 952:955 e.g. 952:955 e.g. 952:955 Ozonation substantially altered the feed water organic composition, reshaped the microbial community (e.g., reduced growth of extracellular polymeric substances (EPS) producers and biofilm formation facilitators), and lowered EPS production and EPS protein/polysaccharides (PN/PS) ratio, consequently leading to the better fouling control. 27665432 2 3 theme pressure 592:599 arg1 of -35 kPa 607:616 a transmembrane pressure (TMP) of -35 kPa 576:616 a transmembrane pressure (TMP) of -35 kPa on Day 433 576:627 The MBRs not only substantially degraded OSPW classical and oxidized NAs, but also demonstrated outstanding membrane fouling control performance (the MBR receiving raw OSPW experienced its first severe fouling with a transmembrane pressure (TMP) of -35 kPa on Day 433). 27665432 3 4 theme OSPW 679:682 arg1 pretreatment 663:674 The mild ozonation (30 mg O3/L) pretreatment 631:674 The mild ozonation (30 mg O3/L) pretreatment of OSPW 631:682 The mild ozonation (30 mg O3/L) pretreatment of OSPW remarkably enhanced OSPW NA degradation, and improved the MBR's fouling control in terms of prolonged long-term slow TMP growth phase and reduced TMP jump frequency. 27665432 5 5 theme sharp 1358:1362 arg1 phase 1373:1377 the sharp TMP rise phase 1354:1377 the sharp TMP rise phase 1354:1377 Examination on fouling behaviors at different HRTs of the raw OSPW MBR indicates that HRT also played a role in determining the dominating fouling mechanism during the sharp TMP rise phase. 27665432 4 6 theme EPS 1095:1097 arg1 PN/PS 1124:1128 PN/PS 1124:1128 PN/PS 1124:1128 Ozonation substantially altered the feed water organic composition, reshaped the microbial community (e.g., reduced growth of extracellular polymeric substances (EPS) producers and biofilm formation facilitators), and lowered EPS production and EPS protein/polysaccharides (PN/PS) ratio, consequently leading to the better fouling control. 27665432 4 6 theme EPS 1095:1097 arg1 protein/polysaccharides 1099:1121 EPS protein/polysaccharides 1095:1121 EPS protein/polysaccharides (PN/PS) ratio 1095:1135 Ozonation substantially altered the feed water organic composition, reshaped the microbial community (e.g., reduced growth of extracellular polymeric substances (EPS) producers and biofilm formation facilitators), and lowered EPS production and EPS protein/polysaccharides (PN/PS) ratio, consequently leading to the better fouling control. 27665432 5 7 theme rise 1368:1371 arg1 phase 1373:1377 the sharp TMP rise phase 1354:1377 the sharp TMP rise phase 1354:1377 Examination on fouling behaviors at different HRTs of the raw OSPW MBR indicates that HRT also played a role in determining the dominating fouling mechanism during the sharp TMP rise phase. 27665432 1 8 theme identical 185:193 arg1 MBRs 232:235 MBRs 232:235 MBRs 232:235 Two identical anoxic-aerobic membrane bioreactors (MBRs) were operated in parallel for 742 consecutive days for raw and ozonated oil sands process-affected water (OSPW) treatment. 27665432 1 8 theme identical 185:193 arg1 bioreactors 219:229 Two identical anoxic-aerobic membrane bioreactors 181:229 Two identical anoxic-aerobic membrane bioreactors (MBRs) 181:236 Two identical anoxic-aerobic membrane bioreactors (MBRs) were operated in parallel for 742 consecutive days for raw and ozonated oil sands process-affected water (OSPW) treatment. 27665432 2 9 theme first 550:554 arg1 fouling 563:569 its first severe fouling 546:569 its first severe fouling 546:569 The MBRs not only substantially degraded OSPW classical and oxidized NAs, but also demonstrated outstanding membrane fouling control performance (the MBR receiving raw OSPW experienced its first severe fouling with a transmembrane pressure (TMP) of -35 kPa on Day 433). 27665432 3 10 theme NA 709:710 arg1 degradation 712:722 OSPW NA degradation 704:722 OSPW NA degradation 704:722 The mild ozonation (30 mg O3/L) pretreatment of OSPW remarkably enhanced OSPW NA degradation, and improved the MBR's fouling control in terms of prolonged long-term slow TMP growth phase and reduced TMP jump frequency. 27665432 1 11 theme membrane 210:217 arg1 MBRs 232:235 MBRs 232:235 MBRs 232:235 Two identical anoxic-aerobic membrane bioreactors (MBRs) were operated in parallel for 742 consecutive days for raw and ozonated oil sands process-affected water (OSPW) treatment. 27665432 1 11 theme membrane 210:217 arg1 bioreactors 219:229 Two identical anoxic-aerobic membrane bioreactors 181:229 Two identical anoxic-aerobic membrane bioreactors (MBRs) 181:236 Two identical anoxic-aerobic membrane bioreactors (MBRs) were operated in parallel for 742 consecutive days for raw and ozonated oil sands process-affected water (OSPW) treatment. 27665432 4 12 theme organic 897:903 arg1 composition 905:915 the feed water organic composition 882:915 the feed water organic composition 882:915 Ozonation substantially altered the feed water organic composition, reshaped the microbial community (e.g., reduced growth of extracellular polymeric substances (EPS) producers and biofilm formation facilitators), and lowered EPS production and EPS protein/polysaccharides (PN/PS) ratio, consequently leading to the better fouling control. 27665432 4 13 theme lowered 1068:1074 arg1 production 1080:1089 lowered EPS production 1068:1089 lowered EPS production 1068:1089 Ozonation substantially altered the feed water organic composition, reshaped the microbial community (e.g., reduced growth of extracellular polymeric substances (EPS) producers and biofilm formation facilitators), and lowered EPS production and EPS protein/polysaccharides (PN/PS) ratio, consequently leading to the better fouling control. 27665432 0 14 theme water 157:161 arg1 treatment 170:178 water (OSPW) treatment 157:178 water (OSPW) treatment 157:178 Effects of ozone pretreatment and operating conditions on membrane fouling behaviors of an anoxic-aerobic membrane bioreactor for oil sands process-affected water (OSPW) treatment. 27665432 6 15 theme membrane 1536:1543 arg1 fouling 1545:1551 membrane fouling 1536:1551 membrane fouling in the MBR for OSPW treatment 1536:1581 Therefore, the results of this study suggest that the low-dose ozone pretreatment is a good option to enhance organic contaminant degradation and alleviate membrane fouling in the MBR for OSPW treatment. 27665432 3 16 theme phase 812:816 arg1 terms 767:771 terms 767:771 terms of prolonged long-term slow TMP growth phase and reduced TMP jump frequency 767:847 The mild ozonation (30 mg O3/L) pretreatment of OSPW remarkably enhanced OSPW NA degradation, and improved the MBR's fouling control in terms of prolonged long-term slow TMP growth phase and reduced TMP jump frequency. 27665432 5 17 from Examination 1190:1200 arg1 behaviors 1213:1221 fouling behaviors 1205:1221 fouling behaviors 1205:1221 Examination on fouling behaviors at different HRTs of the raw OSPW MBR indicates that HRT also played a role in determining the dominating fouling mechanism during the sharp TMP rise phase. 27665432 6 18 from fouling 1545:1551 arg1 MBR 1560:1562 the MBR 1556:1562 the MBR 1556:1562 Therefore, the results of this study suggest that the low-dose ozone pretreatment is a good option to enhance organic contaminant degradation and alleviate membrane fouling in the MBR for OSPW treatment. 27665432 3 19 theme TMP 801:803 arg1 phase 812:816 prolonged long-term slow TMP growth phase 776:816 prolonged long-term slow TMP growth phase 776:816 The mild ozonation (30 mg O3/L) pretreatment of OSPW remarkably enhanced OSPW NA degradation, and improved the MBR's fouling control in terms of prolonged long-term slow TMP growth phase and reduced TMP jump frequency. 27665432 5 20 theme OSPW 1252:1255 arg1 MBR 1257:1259 the raw OSPW MBR 1244:1259 the raw OSPW MBR 1244:1259 Examination on fouling behaviors at different HRTs of the raw OSPW MBR indicates that HRT also played a role in determining the dominating fouling mechanism during the sharp TMP rise phase. 27665432 3 21 theme fouling 748:754 arg1 control 756:762 the MBR's fouling control 738:762 the MBR's fouling control in terms of prolonged long-term slow TMP growth phase and reduced TMP jump frequency 738:847 The mild ozonation (30 mg O3/L) pretreatment of OSPW remarkably enhanced OSPW NA degradation, and improved the MBR's fouling control in terms of prolonged long-term slow TMP growth phase and reduced TMP jump frequency. 27665432 0 22 theme membrane 58:65 arg1 behaviors 75:83 membrane fouling behaviors 58:83 membrane fouling behaviors 58:83 Effects of ozone pretreatment and operating conditions on membrane fouling behaviors of an anoxic-aerobic membrane bioreactor for oil sands process-affected water (OSPW) treatment. 27665432 1 23 theme process-affected 320:335 arg1 treatment 350:358 ozonated oil sands process-affected water (OSPW) treatment 301:358 ozonated oil sands process-affected water (OSPW) treatment 301:358 Two identical anoxic-aerobic membrane bioreactors (MBRs) were operated in parallel for 742 consecutive days for raw and ozonated oil sands process-affected water (OSPW) treatment. 27665432 2 24 theme oxidized 421:428 arg1 NAs 430:432 OSPW classical and oxidized NAs 402:432 OSPW classical and oxidized NAs 402:432 The MBRs not only substantially degraded OSPW classical and oxidized NAs, but also demonstrated outstanding membrane fouling control performance (the MBR receiving raw OSPW experienced its first severe fouling with a transmembrane pressure (TMP) of -35 kPa on Day 433). 27665432 6 25 theme contaminant 1498:1508 arg1 degradation 1510:1520 organic contaminant degradation 1490:1520 organic contaminant degradation 1490:1520 Therefore, the results of this study suggest that the low-dose ozone pretreatment is a good option to enhance organic contaminant degradation and alleviate membrane fouling in the MBR for OSPW treatment. 27665432 3 26 theme jump 834:837 arg1 frequency 839:847 reduced TMP jump frequency 822:847 reduced TMP jump frequency 822:847 The mild ozonation (30 mg O3/L) pretreatment of OSPW remarkably enhanced OSPW NA degradation, and improved the MBR's fouling control in terms of prolonged long-term slow TMP growth phase and reduced TMP jump frequency. 27665432 2 27 theme control 486:492 arg1 performance 494:504 outstanding membrane fouling control performance 457:504 outstanding membrane fouling control performance (the MBR receiving raw OSPW experienced its first severe fouling with a transmembrane pressure (TMP) of -35 kPa on Day 433) 457:628 The MBRs not only substantially degraded OSPW classical and oxidized NAs, but also demonstrated outstanding membrane fouling control performance (the MBR receiving raw OSPW experienced its first severe fouling with a transmembrane pressure (TMP) of -35 kPa on Day 433). 27665432 3 28 theme long-term 786:794 arg1 phase 812:816 prolonged long-term slow TMP growth phase 776:816 prolonged long-term slow TMP growth phase 776:816 The mild ozonation (30 mg O3/L) pretreatment of OSPW remarkably enhanced OSPW NA degradation, and improved the MBR's fouling control in terms of prolonged long-term slow TMP growth phase and reduced TMP jump frequency. 27665432 3 29 theme reduced 822:828 arg1 frequency 839:847 reduced TMP jump frequency 822:847 reduced TMP jump frequency 822:847 The mild ozonation (30 mg O3/L) pretreatment of OSPW remarkably enhanced OSPW NA degradation, and improved the MBR's fouling control in terms of prolonged long-term slow TMP growth phase and reduced TMP jump frequency. 27665432 2 30 theme raw 525:527 arg1 OSPW 529:532 raw OSPW 525:532 raw OSPW experienced its first severe fouling with a transmembrane pressure (TMP) of -35 kPa on Day 433 525:627 The MBRs not only substantially degraded OSPW classical and oxidized NAs, but also demonstrated outstanding membrane fouling control performance (the MBR receiving raw OSPW experienced its first severe fouling with a transmembrane pressure (TMP) of -35 kPa on Day 433). 27665432 0 31 from Effects 0:6 arg1 behaviors 75:83 membrane fouling behaviors 58:83 membrane fouling behaviors 58:83 Effects of ozone pretreatment and operating conditions on membrane fouling behaviors of an anoxic-aerobic membrane bioreactor for oil sands process-affected water (OSPW) treatment. 27665432 0 32 from conditions 44:53 arg1 behaviors 75:83 membrane fouling behaviors 58:83 membrane fouling behaviors 58:83 Effects of ozone pretreatment and operating conditions on membrane fouling behaviors of an anoxic-aerobic membrane bioreactor for oil sands process-affected water (OSPW) treatment. 27665432 0 33 theme membrane 106:113 arg1 bioreactor 115:124 an anoxic-aerobic membrane bioreactor 88:124 an anoxic-aerobic membrane bioreactor for oil sands 88:138 Effects of ozone pretreatment and operating conditions on membrane fouling behaviors of an anoxic-aerobic membrane bioreactor for oil sands process-affected water (OSPW) treatment. 27665432 4 34 theme reduced 958:964 arg1 growth 966:971 reduced growth 958:971 reduced growth of extracellular polymeric substances (EPS) 958:1015 Ozonation substantially altered the feed water organic composition, reshaped the microbial community (e.g., reduced growth of extracellular polymeric substances (EPS) producers and biofilm formation facilitators), and lowered EPS production and EPS protein/polysaccharides (PN/PS) ratio, consequently leading to the better fouling control. 27665432 6 35 theme OSPW 1568:1571 arg1 treatment 1573:1581 OSPW treatment 1568:1581 OSPW treatment 1568:1581 Therefore, the results of this study suggest that the low-dose ozone pretreatment is a good option to enhance organic contaminant degradation and alleviate membrane fouling in the MBR for OSPW treatment. 27665432 4 36 theme polymeric 990:998 arg1 EPS 1012:1014 EPS 1012:1014 EPS 1012:1014 Ozonation substantially altered the feed water organic composition, reshaped the microbial community (e.g., reduced growth of extracellular polymeric substances (EPS) producers and biofilm formation facilitators), and lowered EPS production and EPS protein/polysaccharides (PN/PS) ratio, consequently leading to the better fouling control. 27665432 4 36 theme polymeric 990:998 arg1 substances 1000:1009 extracellular polymeric substances 976:1009 extracellular polymeric substances (EPS) 976:1015 Ozonation substantially altered the feed water organic composition, reshaped the microbial community (e.g., reduced growth of extracellular polymeric substances (EPS) producers and biofilm formation facilitators), and lowered EPS production and EPS protein/polysaccharides (PN/PS) ratio, consequently leading to the better fouling control. 27665432 1 37 theme consecutive 272:282 arg1 days 284:287 742 consecutive days 268:287 742 consecutive days for raw and ozonated oil sands process-affected water (OSPW) treatment 268:358 Two identical anoxic-aerobic membrane bioreactors (MBRs) were operated in parallel for 742 consecutive days for raw and ozonated oil sands process-affected water (OSPW) treatment. 27665432 4 38 theme fouling 1173:1179 arg1 control 1181:1187 the better fouling control 1162:1187 the better fouling control 1162:1187 Ozonation substantially altered the feed water organic composition, reshaped the microbial community (e.g., reduced growth of extracellular polymeric substances (EPS) producers and biofilm formation facilitators), and lowered EPS production and EPS protein/polysaccharides (PN/PS) ratio, consequently leading to the better fouling control. 27665432 0 39 theme ozone 11:15 arg1 pretreatment 17:28 ozone pretreatment 11:28 ozone pretreatment 11:28 Effects of ozone pretreatment and operating conditions on membrane fouling behaviors of an anoxic-aerobic membrane bioreactor for oil sands process-affected water (OSPW) treatment. 27665432 2 40 theme membrane 469:476 arg1 performance 494:504 outstanding membrane fouling control performance 457:504 outstanding membrane fouling control performance (the MBR receiving raw OSPW experienced its first severe fouling with a transmembrane pressure (TMP) of -35 kPa on Day 433) 457:628 The MBRs not only substantially degraded OSPW classical and oxidized NAs, but also demonstrated outstanding membrane fouling control performance (the MBR receiving raw OSPW experienced its first severe fouling with a transmembrane pressure (TMP) of -35 kPa on Day 433). 27665432 2 41 theme OSPW 402:405 arg1 NAs 430:432 OSPW classical and oxidized NAs 402:432 OSPW classical and oxidized NAs 402:432 The MBRs not only substantially degraded OSPW classical and oxidized NAs, but also demonstrated outstanding membrane fouling control performance (the MBR receiving raw OSPW experienced its first severe fouling with a transmembrane pressure (TMP) of -35 kPa on Day 433). 27665432 1 42 theme oil 310:312 arg1 treatment 350:358 ozonated oil sands process-affected water (OSPW) treatment 301:358 ozonated oil sands process-affected water (OSPW) treatment 301:358 Two identical anoxic-aerobic membrane bioreactors (MBRs) were operated in parallel for 742 consecutive days for raw and ozonated oil sands process-affected water (OSPW) treatment. 27665432 4 43 theme formation 1039:1047 arg1 facilitators 1049:1060 biofilm formation facilitators 1031:1060 biofilm formation facilitators 1031:1060 Ozonation substantially altered the feed water organic composition, reshaped the microbial community (e.g., reduced growth of extracellular polymeric substances (EPS) producers and biofilm formation facilitators), and lowered EPS production and EPS protein/polysaccharides (PN/PS) ratio, consequently leading to the better fouling control. 27665432 3 44 theme 30 mg 651:655 arg1 pretreatment 663:674 The mild ozonation (30 mg O3/L) pretreatment 631:674 The mild ozonation (30 mg O3/L) pretreatment of OSPW 631:682 The mild ozonation (30 mg O3/L) pretreatment of OSPW remarkably enhanced OSPW NA degradation, and improved the MBR's fouling control in terms of prolonged long-term slow TMP growth phase and reduced TMP jump frequency. 27665432 2 45 dep performance 494:504 arg1 MBR 511:513 the MBR 507:513 the MBR receiving raw OSPW experienced its first severe fouling with a transmembrane pressure (TMP) of -35 kPa on Day 433 507:627 The MBRs not only substantially degraded OSPW classical and oxidized NAs, but also demonstrated outstanding membrane fouling control performance (the MBR receiving raw OSPW experienced its first severe fouling with a transmembrane pressure (TMP) of -35 kPa on Day 433). 27665432 3 46 theme ozonation 640:648 arg1 pretreatment 663:674 The mild ozonation (30 mg O3/L) pretreatment 631:674 The mild ozonation (30 mg O3/L) pretreatment of OSPW 631:682 The mild ozonation (30 mg O3/L) pretreatment of OSPW remarkably enhanced OSPW NA degradation, and improved the MBR's fouling control in terms of prolonged long-term slow TMP growth phase and reduced TMP jump frequency. 27665432 5 47 theme dominating 1318:1327 arg1 mechanism 1337:1345 the dominating fouling mechanism 1314:1345 the dominating fouling mechanism 1314:1345 Examination on fouling behaviors at different HRTs of the raw OSPW MBR indicates that HRT also played a role in determining the dominating fouling mechanism during the sharp TMP rise phase. 27665432 2 48 theme transmembrane 578:590 arg1 of -35 kPa 607:616 a transmembrane pressure (TMP) of -35 kPa 576:616 a transmembrane pressure (TMP) of -35 kPa on Day 433 576:627 The MBRs not only substantially degraded OSPW classical and oxidized NAs, but also demonstrated outstanding membrane fouling control performance (the MBR receiving raw OSPW experienced its first severe fouling with a transmembrane pressure (TMP) of -35 kPa on Day 433). 27665432 5 49 from HRTs 1236:1239 arg1 Examination 1190:1200 Examination 1190:1200 Examination on fouling behaviors at different HRTs of the raw OSPW MBR 1190:1259 Examination on fouling behaviors at different HRTs of the raw OSPW MBR indicates that HRT also played a role in determining the dominating fouling mechanism during the sharp TMP rise phase. 27665432 3 50 theme OSPW 704:707 arg1 degradation 712:722 OSPW NA degradation 704:722 OSPW NA degradation 704:722 The mild ozonation (30 mg O3/L) pretreatment of OSPW remarkably enhanced OSPW NA degradation, and improved the MBR's fouling control in terms of prolonged long-term slow TMP growth phase and reduced TMP jump frequency. 27665432 4 51 theme protein/polysaccharides 1099:1121 arg1 ratio 1131:1135 EPS protein/polysaccharides (PN/PS) ratio 1095:1135 EPS protein/polysaccharides (PN/PS) ratio 1095:1135 Ozonation substantially altered the feed water organic composition, reshaped the microbial community (e.g., reduced growth of extracellular polymeric substances (EPS) producers and biofilm formation facilitators), and lowered EPS production and EPS protein/polysaccharides (PN/PS) ratio, consequently leading to the better fouling control. 27665432 5 52 theme TMP 1364:1366 arg1 phase 1373:1377 the sharp TMP rise phase 1354:1377 the sharp TMP rise phase 1354:1377 Examination on fouling behaviors at different HRTs of the raw OSPW MBR indicates that HRT also played a role in determining the dominating fouling mechanism during the sharp TMP rise phase. 27665432 6 53 theme good 1467:1470 arg1 option 1472:1477 a good option 1465:1477 a good option to enhance organic contaminant degradation and alleviate membrane fouling in the MBR for OSPW treatment 1465:1581 Therefore, the results of this study suggest that the low-dose ozone pretreatment is a good option to enhance organic contaminant degradation and alleviate membrane fouling in the MBR for OSPW treatment. 27665432 6 53 theme good 1467:1470 arg1 pretreatment 1449:1460 the low-dose ozone pretreatment 1430:1460 the low-dose ozone pretreatment 1430:1460 Therefore, the results of this study suggest that the low-dose ozone pretreatment is a good option to enhance organic contaminant degradation and alleviate membrane fouling in the MBR for OSPW treatment. 27665432 0 54 theme oil 130:132 arg1 sands 134:138 oil sands 130:138 oil sands 130:138 Effects of ozone pretreatment and operating conditions on membrane fouling behaviors of an anoxic-aerobic membrane bioreactor for oil sands process-affected water (OSPW) treatment. 27665432 1 55 theme anoxic-aerobic 195:208 arg1 MBRs 232:235 MBRs 232:235 MBRs 232:235 Two identical anoxic-aerobic membrane bioreactors (MBRs) were operated in parallel for 742 consecutive days for raw and ozonated oil sands process-affected water (OSPW) treatment. 27665432 1 55 theme anoxic-aerobic 195:208 arg1 bioreactors 219:229 Two identical anoxic-aerobic membrane bioreactors 181:229 Two identical anoxic-aerobic membrane bioreactors (MBRs) 181:236 Two identical anoxic-aerobic membrane bioreactors (MBRs) were operated in parallel for 742 consecutive days for raw and ozonated oil sands process-affected water (OSPW) treatment. 27665432 4 56 theme EPS 1076:1078 arg1 production 1080:1089 lowered EPS production 1068:1089 lowered EPS production 1068:1089 Ozonation substantially altered the feed water organic composition, reshaped the microbial community (e.g., reduced growth of extracellular polymeric substances (EPS) producers and biofilm formation facilitators), and lowered EPS production and EPS protein/polysaccharides (PN/PS) ratio, consequently leading to the better fouling control. 27665432 6 57 theme ozone 1443:1447 arg1 option 1472:1477 a good option 1465:1477 a good option to enhance organic contaminant degradation and alleviate membrane fouling in the MBR for OSPW treatment 1465:1581 Therefore, the results of this study suggest that the low-dose ozone pretreatment is a good option to enhance organic contaminant degradation and alleviate membrane fouling in the MBR for OSPW treatment. 27665432 6 57 theme ozone 1443:1447 arg1 pretreatment 1449:1460 the low-dose ozone pretreatment 1430:1460 the low-dose ozone pretreatment 1430:1460 Therefore, the results of this study suggest that the low-dose ozone pretreatment is a good option to enhance organic contaminant degradation and alleviate membrane fouling in the MBR for OSPW treatment. 27665432 4 58 theme water 891:895 arg1 composition 905:915 the feed water organic composition 882:915 the feed water organic composition 882:915 Ozonation substantially altered the feed water organic composition, reshaped the microbial community (e.g., reduced growth of extracellular polymeric substances (EPS) producers and biofilm formation facilitators), and lowered EPS production and EPS protein/polysaccharides (PN/PS) ratio, consequently leading to the better fouling control. 27665432 4 59 theme feed 886:889 arg1 composition 905:915 the feed water organic composition 882:915 the feed water organic composition 882:915 Ozonation substantially altered the feed water organic composition, reshaped the microbial community (e.g., reduced growth of extracellular polymeric substances (EPS) producers and biofilm formation facilitators), and lowered EPS production and EPS protein/polysaccharides (PN/PS) ratio, consequently leading to the better fouling control. 27665432 4 60 dep community 941:949 arg1 producers 1017:1025 producers 1017:1025 producers 1017:1025 Ozonation substantially altered the feed water organic composition, reshaped the microbial community (e.g., reduced growth of extracellular polymeric substances (EPS) producers and biofilm formation facilitators), and lowered EPS production and EPS protein/polysaccharides (PN/PS) ratio, consequently leading to the better fouling control. 27665432 4 60 dep community 941:949 arg1 facilitators 1049:1060 biofilm formation facilitators 1031:1060 biofilm formation facilitators 1031:1060 Ozonation substantially altered the feed water organic composition, reshaped the microbial community (e.g., reduced growth of extracellular polymeric substances (EPS) producers and biofilm formation facilitators), and lowered EPS production and EPS protein/polysaccharides (PN/PS) ratio, consequently leading to the better fouling control. 27665432 2 61 theme severe 556:561 arg1 fouling 563:569 its first severe fouling 546:569 its first severe fouling 546:569 The MBRs not only substantially degraded OSPW classical and oxidized NAs, but also demonstrated outstanding membrane fouling control performance (the MBR receiving raw OSPW experienced its first severe fouling with a transmembrane pressure (TMP) of -35 kPa on Day 433). 27665432 5 62 theme raw 1248:1250 arg1 MBR 1257:1259 the raw OSPW MBR 1244:1259 the raw OSPW MBR 1244:1259 Examination on fouling behaviors at different HRTs of the raw OSPW MBR indicates that HRT also played a role in determining the dominating fouling mechanism during the sharp TMP rise phase. 27665432 0 63 theme fouling 67:73 arg1 behaviors 75:83 membrane fouling behaviors 58:83 membrane fouling behaviors 58:83 Effects of ozone pretreatment and operating conditions on membrane fouling behaviors of an anoxic-aerobic membrane bioreactor for oil sands process-affected water (OSPW) treatment. 27665432 3 64 theme growth 805:810 arg1 phase 812:816 prolonged long-term slow TMP growth phase 776:816 prolonged long-term slow TMP growth phase 776:816 The mild ozonation (30 mg O3/L) pretreatment of OSPW remarkably enhanced OSPW NA degradation, and improved the MBR's fouling control in terms of prolonged long-term slow TMP growth phase and reduced TMP jump frequency. 27665432 4 65 theme microbial 931:939 arg1 community 941:949 the microbial community 927:949 reshaped the microbial community (e.g., reduced growth of extracellular polymeric substances (EPS) producers and biofilm formation facilitators) 918:1061 Ozonation substantially altered the feed water organic composition, reshaped the microbial community (e.g., reduced growth of extracellular polymeric substances (EPS) producers and biofilm formation facilitators), and lowered EPS production and EPS protein/polysaccharides (PN/PS) ratio, consequently leading to the better fouling control. 27665432 1 66 theme water 337:341 arg1 treatment 350:358 ozonated oil sands process-affected water (OSPW) treatment 301:358 ozonated oil sands process-affected water (OSPW) treatment 301:358 Two identical anoxic-aerobic membrane bioreactors (MBRs) were operated in parallel for 742 consecutive days for raw and ozonated oil sands process-affected water (OSPW) treatment. 27665432 6 67 theme organic 1490:1496 arg1 degradation 1510:1520 organic contaminant degradation 1490:1520 organic contaminant degradation 1490:1520 Therefore, the results of this study suggest that the low-dose ozone pretreatment is a good option to enhance organic contaminant degradation and alleviate membrane fouling in the MBR for OSPW treatment. 27665432 3 68 theme frequency 839:847 arg1 terms 767:771 terms 767:771 terms of prolonged long-term slow TMP growth phase and reduced TMP jump frequency 767:847 The mild ozonation (30 mg O3/L) pretreatment of OSPW remarkably enhanced OSPW NA degradation, and improved the MBR's fouling control in terms of prolonged long-term slow TMP growth phase and reduced TMP jump frequency. 27665432 2 69 theme fouling 478:484 arg1 performance 494:504 outstanding membrane fouling control performance 457:504 outstanding membrane fouling control performance (the MBR receiving raw OSPW experienced its first severe fouling with a transmembrane pressure (TMP) of -35 kPa on Day 433) 457:628 The MBRs not only substantially degraded OSPW classical and oxidized NAs, but also demonstrated outstanding membrane fouling control performance (the MBR receiving raw OSPW experienced its first severe fouling with a transmembrane pressure (TMP) of -35 kPa on Day 433). 27665432 5 70 theme different 1226:1234 arg1 HRTs 1236:1239 different HRTs 1226:1239 different HRTs of the raw OSPW MBR 1226:1259 Examination on fouling behaviors at different HRTs of the raw OSPW MBR indicates that HRT also played a role in determining the dominating fouling mechanism during the sharp TMP rise phase. 27665432 3 71 theme slow 796:799 arg1 phase 812:816 prolonged long-term slow TMP growth phase 776:816 prolonged long-term slow TMP growth phase 776:816 The mild ozonation (30 mg O3/L) pretreatment of OSPW remarkably enhanced OSPW NA degradation, and improved the MBR's fouling control in terms of prolonged long-term slow TMP growth phase and reduced TMP jump frequency. 27665432 0 72 theme anoxic-aerobic 91:104 arg1 bioreactor 115:124 an anoxic-aerobic membrane bioreactor 88:124 an anoxic-aerobic membrane bioreactor for oil sands 88:138 Effects of ozone pretreatment and operating conditions on membrane fouling behaviors of an anoxic-aerobic membrane bioreactor for oil sands process-affected water (OSPW) treatment. 27665432 1 73 theme OSPW 344:347 arg1 treatment 350:358 ozonated oil sands process-affected water (OSPW) treatment 301:358 ozonated oil sands process-affected water (OSPW) treatment 301:358 Two identical anoxic-aerobic membrane bioreactors (MBRs) were operated in parallel for 742 consecutive days for raw and ozonated oil sands process-affected water (OSPW) treatment. 27665432 3 74 theme TMP 830:832 arg1 frequency 839:847 reduced TMP jump frequency 822:847 reduced TMP jump frequency 822:847 The mild ozonation (30 mg O3/L) pretreatment of OSPW remarkably enhanced OSPW NA degradation, and improved the MBR's fouling control in terms of prolonged long-term slow TMP growth phase and reduced TMP jump frequency. 27665432 3 75 theme prolonged 776:784 arg1 phase 812:816 prolonged long-term slow TMP growth phase 776:816 prolonged long-term slow TMP growth phase 776:816 The mild ozonation (30 mg O3/L) pretreatment of OSPW remarkably enhanced OSPW NA degradation, and improved the MBR's fouling control in terms of prolonged long-term slow TMP growth phase and reduced TMP jump frequency. 27665432 0 76 theme bioreactor 115:124 arg1 Effects 0:6 Effects 0:6 Effects of ozone pretreatment 0:28 Effects of ozone pretreatment and operating conditions on membrane fouling behaviors of an anoxic-aerobic membrane bioreactor for oil sands process-affected water (OSPW) treatment. 27665432 0 76 theme bioreactor 115:124 arg1 conditions 44:53 operating conditions 34:53 operating conditions 34:53 Effects of ozone pretreatment and operating conditions on membrane fouling behaviors of an anoxic-aerobic membrane bioreactor for oil sands process-affected water (OSPW) treatment. 27665432 4 77 theme reshaped 918:925 arg1 community 941:949 the microbial community 927:949 reshaped the microbial community (e.g., reduced growth of extracellular polymeric substances (EPS) producers and biofilm formation facilitators) 918:1061 Ozonation substantially altered the feed water organic composition, reshaped the microbial community (e.g., reduced growth of extracellular polymeric substances (EPS) producers and biofilm formation facilitators), and lowered EPS production and EPS protein/polysaccharides (PN/PS) ratio, consequently leading to the better fouling control. 27665432 4 78 theme better 1166:1171 arg1 control 1181:1187 the better fouling control 1162:1187 the better fouling control 1162:1187 Ozonation substantially altered the feed water organic composition, reshaped the microbial community (e.g., reduced growth of extracellular polymeric substances (EPS) producers and biofilm formation facilitators), and lowered EPS production and EPS protein/polysaccharides (PN/PS) ratio, consequently leading to the better fouling control. 27665432 4 79 theme extracellular 976:988 arg1 EPS 1012:1014 EPS 1012:1014 EPS 1012:1014 Ozonation substantially altered the feed water organic composition, reshaped the microbial community (e.g., reduced growth of extracellular polymeric substances (EPS) producers and biofilm formation facilitators), and lowered EPS production and EPS protein/polysaccharides (PN/PS) ratio, consequently leading to the better fouling control. 27665432 4 79 theme extracellular 976:988 arg1 substances 1000:1009 extracellular polymeric substances 976:1009 extracellular polymeric substances (EPS) 976:1015 Ozonation substantially altered the feed water organic composition, reshaped the microbial community (e.g., reduced growth of extracellular polymeric substances (EPS) producers and biofilm formation facilitators), and lowered EPS production and EPS protein/polysaccharides (PN/PS) ratio, consequently leading to the better fouling control. 27665432 5 80 theme MBR 1257:1259 arg1 HRTs 1236:1239 different HRTs 1226:1239 different HRTs of the raw OSPW MBR 1226:1259 Examination on fouling behaviors at different HRTs of the raw OSPW MBR indicates that HRT also played a role in determining the dominating fouling mechanism during the sharp TMP rise phase. 27665432 0 81 theme pretreatment 17:28 arg1 Effects 0:6 Effects 0:6 Effects of ozone pretreatment 0:28 Effects of ozone pretreatment and operating conditions on membrane fouling behaviors of an anoxic-aerobic membrane bioreactor for oil sands process-affected water (OSPW) treatment. 27665432 0 81 theme pretreatment 17:28 arg1 conditions 44:53 operating conditions 34:53 operating conditions 34:53 Effects of ozone pretreatment and operating conditions on membrane fouling behaviors of an anoxic-aerobic membrane bioreactor for oil sands process-affected water (OSPW) treatment. 27665432 4 82 theme substances 1000:1009 arg1 growth 966:971 reduced growth 958:971 reduced growth of extracellular polymeric substances (EPS) 958:1015 Ozonation substantially altered the feed water organic composition, reshaped the microbial community (e.g., reduced growth of extracellular polymeric substances (EPS) producers and biofilm formation facilitators), and lowered EPS production and EPS protein/polysaccharides (PN/PS) ratio, consequently leading to the better fouling control. 27665432 2 83 theme classical 407:415 arg1 NAs 430:432 OSPW classical and oxidized NAs 402:432 OSPW classical and oxidized NAs 402:432 The MBRs not only substantially degraded OSPW classical and oxidized NAs, but also demonstrated outstanding membrane fouling control performance (the MBR receiving raw OSPW experienced its first severe fouling with a transmembrane pressure (TMP) of -35 kPa on Day 433). 27665432 0 84 theme operating 34:42 arg1 conditions 44:53 operating conditions 34:53 operating conditions 34:53 Effects of ozone pretreatment and operating conditions on membrane fouling behaviors of an anoxic-aerobic membrane bioreactor for oil sands process-affected water (OSPW) treatment. 27665432 2 85 theme outstanding 457:467 arg1 performance 494:504 outstanding membrane fouling control performance 457:504 outstanding membrane fouling control performance (the MBR receiving raw OSPW experienced its first severe fouling with a transmembrane pressure (TMP) of -35 kPa on Day 433) 457:628 The MBRs not only substantially degraded OSPW classical and oxidized NAs, but also demonstrated outstanding membrane fouling control performance (the MBR receiving raw OSPW experienced its first severe fouling with a transmembrane pressure (TMP) of -35 kPa on Day 433). 27665432 2 86 from of -35 kPa 607:616 arg1 Day 621:623 Day 433 621:627 Day 433 621:627 The MBRs not only substantially degraded OSPW classical and oxidized NAs, but also demonstrated outstanding membrane fouling control performance (the MBR receiving raw OSPW experienced its first severe fouling with a transmembrane pressure (TMP) of -35 kPa on Day 433). 27665432 5 87 theme fouling 1329:1335 arg1 mechanism 1337:1345 the dominating fouling mechanism 1314:1345 the dominating fouling mechanism 1314:1345 Examination on fouling behaviors at different HRTs of the raw OSPW MBR indicates that HRT also played a role in determining the dominating fouling mechanism during the sharp TMP rise phase. 27665432 1 88 theme ozonated 301:308 arg1 treatment 350:358 ozonated oil sands process-affected water (OSPW) treatment 301:358 ozonated oil sands process-affected water (OSPW) treatment 301:358 Two identical anoxic-aerobic membrane bioreactors (MBRs) were operated in parallel for 742 consecutive days for raw and ozonated oil sands process-affected water (OSPW) treatment. 27665432 3 89 from control 756:762 arg1 terms 767:771 terms 767:771 terms of prolonged long-term slow TMP growth phase and reduced TMP jump frequency 767:847 The mild ozonation (30 mg O3/L) pretreatment of OSPW remarkably enhanced OSPW NA degradation, and improved the MBR's fouling control in terms of prolonged long-term slow TMP growth phase and reduced TMP jump frequency. 27665432 6 90 theme low-dose 1434:1441 arg1 option 1472:1477 a good option 1465:1477 a good option to enhance organic contaminant degradation and alleviate membrane fouling in the MBR for OSPW treatment 1465:1581 Therefore, the results of this study suggest that the low-dose ozone pretreatment is a good option to enhance organic contaminant degradation and alleviate membrane fouling in the MBR for OSPW treatment. 27665432 6 90 theme low-dose 1434:1441 arg1 pretreatment 1449:1460 the low-dose ozone pretreatment 1430:1460 the low-dose ozone pretreatment 1430:1460 Therefore, the results of this study suggest that the low-dose ozone pretreatment is a good option to enhance organic contaminant degradation and alleviate membrane fouling in the MBR for OSPW treatment. 27665432 1 91 theme sands 314:318 arg1 treatment 350:358 ozonated oil sands process-affected water (OSPW) treatment 301:358 ozonated oil sands process-affected water (OSPW) treatment 301:358 Two identical anoxic-aerobic membrane bioreactors (MBRs) were operated in parallel for 742 consecutive days for raw and ozonated oil sands process-affected water (OSPW) treatment. 27665432 4 92 theme biofilm 1031:1037 arg1 facilitators 1049:1060 biofilm formation facilitators 1031:1060 biofilm formation facilitators 1031:1060 Ozonation substantially altered the feed water organic composition, reshaped the microbial community (e.g., reduced growth of extracellular polymeric substances (EPS) producers and biofilm formation facilitators), and lowered EPS production and EPS protein/polysaccharides (PN/PS) ratio, consequently leading to the better fouling control. 27665432 3 93 theme mild 635:638 arg1 pretreatment 663:674 The mild ozonation (30 mg O3/L) pretreatment 631:674 The mild ozonation (30 mg O3/L) pretreatment of OSPW 631:682 The mild ozonation (30 mg O3/L) pretreatment of OSPW remarkably enhanced OSPW NA degradation, and improved the MBR's fouling control in terms of prolonged long-term slow TMP growth phase and reduced TMP jump frequency. 27665432 6 94 theme study 1411:1415 arg1 results 1395:1401 the results 1391:1401 the results of this study 1391:1415 Therefore, the results of this study suggest that the low-dose ozone pretreatment is a good option to enhance organic contaminant degradation and alleviate membrane fouling in the MBR for OSPW treatment. 27665432 5 95 theme fouling 1205:1211 arg1 behaviors 1213:1221 fouling behaviors 1205:1221 fouling behaviors 1205:1221 Examination on fouling behaviors at different HRTs of the raw OSPW MBR indicates that HRT also played a role in determining the dominating fouling mechanism during the sharp TMP rise phase. 26927821 9 0 theme structural 1499:1508 arg1 changes 1510:1516 structural changes 1499:1516 structural changes 1499:1516 The results concerning structural changes suggested that the observed formation of hydrogen bonds in the β-structures can be connected with aggregation or abnormal folding. 26927821 5 1 dep 18 972:973 arg1 to 969:970 to 969:970 to 969:970 For this aim the bread dough at 500 FU consistency was made of a blend of wheat starch and wheat gluten as well as the fiber, the content of which ranged from 3 to 18% w/w. 26927821 2 2 theme polysaccharides 356:370 arg1 source 346:351 a source 344:351 a source 344:351 The dietary fiber additives are regarded as a source of polysaccharides and antioxidants, which have positive effects on human health. 26927821 2 2 theme polysaccharides 356:370 arg1 additives 318:326 The dietary fiber additives 300:326 The dietary fiber additives 300:326 The dietary fiber additives are regarded as a source of polysaccharides and antioxidants, which have positive effects on human health. 26927821 11 3 from Changes 1709:1715 arg1 loss 1727:1730 weight loss 1720:1730 weight loss 1720:1730 Changes in weight loss indicated the formation of a more complex and strong gluten network. 26927821 1 4 theme baking 283:288 arg1 industry 290:297 the baking industry 279:297 the baking industry 279:297 Interactions between gluten proteins and dietary fiber supplements at the stage of bread dough formation are crucial in the baking industry. 26927821 3 5 from reduction 486:494 arg1 quality 503:509 its quality 499:509 its quality 499:509 The fiber enrichment of bread causes a significant reduction in its quality, which is connected with changes in the structure of gluten proteins. 26927821 1 6 theme dietary 200:206 arg1 supplements 214:224 dietary fiber supplements 200:224 dietary fiber supplements 200:224 Interactions between gluten proteins and dietary fiber supplements at the stage of bread dough formation are crucial in the baking industry. 26927821 4 7 theme commercial 671:680 arg1 fibers 690:695 seven commercial dietary fibers 665:695 seven commercial dietary fibers (fruit, vegetable, and cereal) 665:726 Changes in the structure of gluten proteins and their thermal properties induced by seven commercial dietary fibers (fruit, vegetable, and cereal) were studied by FT-Raman spectroscopy and thermogravimetry (TGA), respectively. 26927821 3 8 theme proteins 571:578 arg1 structure 551:559 the structure 547:559 the structure of gluten proteins 547:578 The fiber enrichment of bread causes a significant reduction in its quality, which is connected with changes in the structure of gluten proteins. 26927821 5 9 theme FU 844:845 arg1 consistency 847:857 500 FU consistency 840:857 500 FU consistency 840:857 For this aim the bread dough at 500 FU consistency was made of a blend of wheat starch and wheat gluten as well as the fiber, the content of which ranged from 3 to 18% w/w. 26927821 9 10 theme hydrogen 1559:1566 arg1 bonds 1568:1572 hydrogen bonds 1559:1572 hydrogen bonds 1559:1572 The results concerning structural changes suggested that the observed formation of hydrogen bonds in the β-structures can be connected with aggregation or abnormal folding. 26927821 5 11 theme w/w 976:978 arg1 % 974:974 3 to 18% w/w 967:978 3 to 18% w/w 967:978 For this aim the bread dough at 500 FU consistency was made of a blend of wheat starch and wheat gluten as well as the fiber, the content of which ranged from 3 to 18% w/w. 26927821 2 12 theme fiber 312:316 arg1 source 346:351 a source 344:351 a source 344:351 The dietary fiber additives are regarded as a source of polysaccharides and antioxidants, which have positive effects on human health. 26927821 2 12 theme fiber 312:316 arg1 additives 318:326 The dietary fiber additives 300:326 The dietary fiber additives 300:326 The dietary fiber additives are regarded as a source of polysaccharides and antioxidants, which have positive effects on human health. 26927821 1 13 from stage 233:237 arg1 Interactions 159:170 Interactions 159:170 Interactions between gluten proteins and dietary fiber supplements at the stage of bread dough formation 159:262 Interactions between gluten proteins and dietary fiber supplements at the stage of bread dough formation are crucial in the baking industry. 26927821 7 14 dep β-turns 1244:1250 arg1 -1 1270:1271 -1 1270:1271 -1 1270:1271 The most noticeable changes were observed in the regions connected with hydrogen-bonded β-sheets (1614 and 1684 cm(-1)) and β-turns (1640 and 1657 cm(-1)). 26927821 7 14 dep β-turns 1244:1250 arg1 cm 1267:1268 1640 and 1657 cm 1253:1268 1640 and 1657 cm(-1) 1253:1272 The most noticeable changes were observed in the regions connected with hydrogen-bonded β-sheets (1614 and 1684 cm(-1)) and β-turns (1640 and 1657 cm(-1)). 26927821 8 15 located observed 1290:1297 arg2 changes 1282:1288 Other changes 1276:1288 Other changes 1276:1288 Other changes observed in the gluten structure, concerning other β-structures, conformation of disulfide bridges, and aromatic amino acid microenvironment, depend on the fibers' chemical composition. 26927821 8 15 located observed 1290:1297 arg1 structure 1313:1321 the gluten structure 1302:1321 the gluten structure 1302:1321 Other changes observed in the gluten structure, concerning other β-structures, conformation of disulfide bridges, and aromatic amino acid microenvironment, depend on the fibers' chemical composition. 26927821 5 16 theme wheat 882:886 arg1 starch 888:893 wheat starch 882:893 wheat starch 882:893 For this aim the bread dough at 500 FU consistency was made of a blend of wheat starch and wheat gluten as well as the fiber, the content of which ranged from 3 to 18% w/w. 26927821 6 17 theme gluten 1103:1108 arg1 proteins 1110:1117 gluten proteins 1103:1117 gluten proteins 1103:1117 The obtained results revealed that all dietary fibers apart from oat caused similar changes in the secondary structure of gluten proteins. 26927821 0 18 from Changes 22:28 arg1 Structure 37:45 Structure 37:45 Structure 37:45 Dietary Fiber-Induced Changes in the Structure and Thermal Properties of Gluten Proteins Studied by Fourier Transform-Raman Spectroscopy and Thermogravimetry. 26927821 0 18 from Changes 22:28 arg1 Properties 59:68 Thermal Properties 51:68 Thermal Properties 51:68 Dietary Fiber-Induced Changes in the Structure and Thermal Properties of Gluten Proteins Studied by Fourier Transform-Raman Spectroscopy and Thermogravimetry. 26927821 3 19 from changes 536:542 arg1 structure 551:559 the structure 547:559 the structure of gluten proteins 547:578 The fiber enrichment of bread causes a significant reduction in its quality, which is connected with changes in the structure of gluten proteins. 26927821 0 20 theme Gluten 73:78 arg1 Proteins 80:87 Gluten Proteins 73:87 Gluten Proteins 73:87 Dietary Fiber-Induced Changes in the Structure and Thermal Properties of Gluten Proteins Studied by Fourier Transform-Raman Spectroscopy and Thermogravimetry. 26927821 7 21 located observed 1153:1160 arg2 changes 1140:1146 The most noticeable changes 1120:1146 The most noticeable changes 1120:1146 The most noticeable changes were observed in the regions connected with hydrogen-bonded β-sheets (1614 and 1684 cm(-1)) and β-turns (1640 and 1657 cm(-1)). 26927821 7 21 located observed 1153:1160 arg1 regions 1169:1175 the regions 1165:1175 the regions connected with hydrogen-bonded β-sheets (1614 and 1684 cm(-1)) and β-turns (1640 and 1657 cm(-1)) 1165:1273 The most noticeable changes were observed in the regions connected with hydrogen-bonded β-sheets (1614 and 1684 cm(-1)) and β-turns (1640 and 1657 cm(-1)). 26927821 4 22 theme FT-Raman 744:751 arg1 spectroscopy 753:764 FT-Raman spectroscopy 744:764 FT-Raman spectroscopy 744:764 Changes in the structure of gluten proteins and their thermal properties induced by seven commercial dietary fibers (fruit, vegetable, and cereal) were studied by FT-Raman spectroscopy and thermogravimetry (TGA), respectively. 26927821 5 23 from consistency 847:857 arg1 dough 831:835 the bread dough 821:835 the bread dough at 500 FU consistency 821:857 For this aim the bread dough at 500 FU consistency was made of a blend of wheat starch and wheat gluten as well as the fiber, the content of which ranged from 3 to 18% w/w. 26927821 8 24 theme disulfide 1371:1379 arg1 bridges 1381:1387 disulfide bridges 1371:1387 disulfide bridges 1371:1387 Other changes observed in the gluten structure, concerning other β-structures, conformation of disulfide bridges, and aromatic amino acid microenvironment, depend on the fibers' chemical composition. 26927821 11 25 theme strong 1778:1783 arg1 network 1792:1798 a more complex and strong gluten network 1759:1798 a more complex and strong gluten network 1759:1798 Changes in weight loss indicated the formation of a more complex and strong gluten network. 26927821 0 26 theme Fourier 100:106 arg1 Spectroscopy 124:135 Fourier Transform-Raman Spectroscopy 100:135 Fourier Transform-Raman Spectroscopy 100:135 Dietary Fiber-Induced Changes in the Structure and Thermal Properties of Gluten Proteins Studied by Fourier Transform-Raman Spectroscopy and Thermogravimetry. 26927821 11 27 theme complex 1766:1772 arg1 network 1792:1798 a more complex and strong gluten network 1759:1798 a more complex and strong gluten network 1759:1798 Changes in weight loss indicated the formation of a more complex and strong gluten network. 26927821 0 28 theme Dietary 0:6 arg1 Changes 22:28 Dietary Fiber-Induced Changes 0:28 Dietary Fiber-Induced Changes in the Structure and Thermal Properties of Gluten Proteins 0:87 Dietary Fiber-Induced Changes in the Structure and Thermal Properties of Gluten Proteins Studied by Fourier Transform-Raman Spectroscopy and Thermogravimetry. 26927821 8 29 theme aromatic 1394:1401 arg1 microenvironment 1414:1429 aromatic amino acid microenvironment 1394:1429 aromatic amino acid microenvironment 1394:1429 Other changes observed in the gluten structure, concerning other β-structures, conformation of disulfide bridges, and aromatic amino acid microenvironment, depend on the fibers' chemical composition. 26927821 5 30 theme gluten 905:910 arg1 blend 873:877 a blend 871:877 a blend of wheat starch and wheat gluten as well as the fiber, the content of which ranged from 3 to 18% w/w 871:978 For this aim the bread dough at 500 FU consistency was made of a blend of wheat starch and wheat gluten as well as the fiber, the content of which ranged from 3 to 18% w/w. 26927821 8 31 theme acid 1409:1412 arg1 microenvironment 1414:1429 aromatic amino acid microenvironment 1394:1429 aromatic amino acid microenvironment 1394:1429 Other changes observed in the gluten structure, concerning other β-structures, conformation of disulfide bridges, and aromatic amino acid microenvironment, depend on the fibers' chemical composition. 26927821 2 32 theme human 421:425 arg1 health 427:432 human health 421:432 human health 421:432 The dietary fiber additives are regarded as a source of polysaccharides and antioxidants, which have positive effects on human health. 26927821 11 33 theme network 1792:1798 arg1 formation 1746:1754 the formation 1742:1754 the formation of a more complex and strong gluten network 1742:1798 Changes in weight loss indicated the formation of a more complex and strong gluten network. 26927821 7 34 theme hydrogen-bonded 1192:1206 arg1 β-sheets 1208:1215 hydrogen-bonded β-sheets 1192:1215 hydrogen-bonded β-sheets (1614 and 1684 cm(-1)) 1192:1238 The most noticeable changes were observed in the regions connected with hydrogen-bonded β-sheets (1614 and 1684 cm(-1)) and β-turns (1640 and 1657 cm(-1)). 26927821 11 35 theme weight 1720:1725 arg1 loss 1727:1730 weight loss 1720:1730 weight loss 1720:1730 Changes in weight loss indicated the formation of a more complex and strong gluten network. 26927821 1 36 theme bread 242:246 arg1 formation 254:262 bread dough formation 242:262 bread dough formation 242:262 Interactions between gluten proteins and dietary fiber supplements at the stage of bread dough formation are crucial in the baking industry. 26927821 6 37 theme dietary 1020:1026 arg1 fibers 1028:1033 all dietary fibers 1016:1033 all dietary fibers apart from oat 1016:1048 The obtained results revealed that all dietary fibers apart from oat caused similar changes in the secondary structure of gluten proteins. 26927821 1 38 theme formation 254:262 arg1 stage 233:237 the stage 229:237 the stage of bread dough formation 229:262 Interactions between gluten proteins and dietary fiber supplements at the stage of bread dough formation are crucial in the baking industry. 26927821 8 39 theme chemical 1454:1461 arg1 composition 1463:1473 the fibers' chemical composition 1442:1473 the fibers' chemical composition 1442:1473 Other changes observed in the gluten structure, concerning other β-structures, conformation of disulfide bridges, and aromatic amino acid microenvironment, depend on the fibers' chemical composition. 26927821 2 40 theme dietary 304:310 arg1 source 346:351 a source 344:351 a source 344:351 The dietary fiber additives are regarded as a source of polysaccharides and antioxidants, which have positive effects on human health. 26927821 2 40 theme dietary 304:310 arg1 additives 318:326 The dietary fiber additives 300:326 The dietary fiber additives 300:326 The dietary fiber additives are regarded as a source of polysaccharides and antioxidants, which have positive effects on human health. 26927821 6 41 theme secondary 1080:1088 arg1 structure 1090:1098 the secondary structure 1076:1098 the secondary structure of gluten proteins 1076:1117 The obtained results revealed that all dietary fibers apart from oat caused similar changes in the secondary structure of gluten proteins. 26927821 5 42 theme 500 840:842 arg1 FU 844:845 FU 844:845 FU 844:845 For this aim the bread dough at 500 FU consistency was made of a blend of wheat starch and wheat gluten as well as the fiber, the content of which ranged from 3 to 18% w/w. 26927821 3 43 theme bread 459:463 arg1 enrichment 445:454 The fiber enrichment 435:454 The fiber enrichment of bread 435:463 The fiber enrichment of bread causes a significant reduction in its quality, which is connected with changes in the structure of gluten proteins. 26927821 9 44 theme observed 1537:1544 arg1 formation 1546:1554 the observed formation 1533:1554 the observed formation of hydrogen bonds in the β-structures 1533:1592 The results concerning structural changes suggested that the observed formation of hydrogen bonds in the β-structures can be connected with aggregation or abnormal folding. 26927821 7 45 theme most 1124:1127 arg1 changes 1140:1146 The most noticeable changes 1120:1146 The most noticeable changes 1120:1146 The most noticeable changes were observed in the regions connected with hydrogen-bonded β-sheets (1614 and 1684 cm(-1)) and β-turns (1640 and 1657 cm(-1)). 26927821 1 46 from industry 290:297 arg1 crucial 268:274 crucial 268:274 crucial 268:274 Interactions between gluten proteins and dietary fiber supplements at the stage of bread dough formation are crucial in the baking industry. 26927821 3 47 theme gluten 564:569 arg1 proteins 571:578 gluten proteins 564:578 gluten proteins 564:578 The fiber enrichment of bread causes a significant reduction in its quality, which is connected with changes in the structure of gluten proteins. 26927821 1 48 theme fiber 208:212 arg1 supplements 214:224 dietary fiber supplements 200:224 dietary fiber supplements 200:224 Interactions between gluten proteins and dietary fiber supplements at the stage of bread dough formation are crucial in the baking industry. 26927821 9 49 from formation 1546:1554 arg1 β-structures 1581:1592 the β-structures 1577:1592 the β-structures 1577:1592 The results concerning structural changes suggested that the observed formation of hydrogen bonds in the β-structures can be connected with aggregation or abnormal folding. 26927821 6 50 theme similar 1057:1063 arg1 changes 1065:1071 similar changes 1057:1071 similar changes 1057:1071 The obtained results revealed that all dietary fibers apart from oat caused similar changes in the secondary structure of gluten proteins. 26927821 9 51 theme bonds 1568:1572 arg1 formation 1546:1554 the observed formation 1533:1554 the observed formation of hydrogen bonds in the β-structures 1533:1592 The results concerning structural changes suggested that the observed formation of hydrogen bonds in the β-structures can be connected with aggregation or abnormal folding. 26927821 1 52 from crucial 268:274 arg1 industry 290:297 the baking industry 279:297 the baking industry 279:297 Interactions between gluten proteins and dietary fiber supplements at the stage of bread dough formation are crucial in the baking industry. 26927821 2 53 contain have 396:399 arg1 source 346:351 a source 344:351 a source 344:351 The dietary fiber additives are regarded as a source of polysaccharides and antioxidants, which have positive effects on human health. 26927821 2 53 contain have 396:399 arg1 additives 318:326 The dietary fiber additives 300:326 The dietary fiber additives 300:326 The dietary fiber additives are regarded as a source of polysaccharides and antioxidants, which have positive effects on human health. 26927821 2 53 contain have 396:399 arg2 effects 410:416 positive effects 401:416 positive effects 401:416 The dietary fiber additives are regarded as a source of polysaccharides and antioxidants, which have positive effects on human health. 26927821 10 54 theme thermogravimetric 1682:1698 arg1 results 1700:1706 thermogravimetric results 1682:1706 thermogravimetric results 1682:1706 This hypothesis was confirmed by thermogravimetric results. 26927821 8 55 theme gluten 1306:1311 arg1 structure 1313:1321 the gluten structure 1302:1321 the gluten structure 1302:1321 Other changes observed in the gluten structure, concerning other β-structures, conformation of disulfide bridges, and aromatic amino acid microenvironment, depend on the fibers' chemical composition. 26927821 4 56 theme thermal 635:641 arg1 properties 643:652 their thermal properties 629:652 their thermal properties 629:652 Changes in the structure of gluten proteins and their thermal properties induced by seven commercial dietary fibers (fruit, vegetable, and cereal) were studied by FT-Raman spectroscopy and thermogravimetry (TGA), respectively. 26927821 5 57 theme fiber 927:931 arg1 blend 873:877 a blend 871:877 a blend of wheat starch and wheat gluten as well as the fiber, the content of which ranged from 3 to 18% w/w 871:978 For this aim the bread dough at 500 FU consistency was made of a blend of wheat starch and wheat gluten as well as the fiber, the content of which ranged from 3 to 18% w/w. 26927821 5 57 theme fiber 927:931 arg1 content 938:944 the content 934:944 the content 934:944 For this aim the bread dough at 500 FU consistency was made of a blend of wheat starch and wheat gluten as well as the fiber, the content of which ranged from 3 to 18% w/w. 26927821 8 58 theme other 1335:1339 arg1 β-structures 1341:1352 other β-structures 1335:1352 other β-structures 1335:1352 Other changes observed in the gluten structure, concerning other β-structures, conformation of disulfide bridges, and aromatic amino acid microenvironment, depend on the fibers' chemical composition. 26927821 6 59 theme proteins 1110:1117 arg1 structure 1090:1098 the secondary structure 1076:1098 the secondary structure of gluten proteins 1076:1117 The obtained results revealed that all dietary fibers apart from oat caused similar changes in the secondary structure of gluten proteins. 26927821 7 60 theme noticeable 1129:1138 arg1 changes 1140:1146 The most noticeable changes 1120:1146 The most noticeable changes 1120:1146 The most noticeable changes were observed in the regions connected with hydrogen-bonded β-sheets (1614 and 1684 cm(-1)) and β-turns (1640 and 1657 cm(-1)). 26927821 4 61 theme dietary 682:688 arg1 fibers 690:695 seven commercial dietary fibers 665:695 seven commercial dietary fibers (fruit, vegetable, and cereal) 665:726 Changes in the structure of gluten proteins and their thermal properties induced by seven commercial dietary fibers (fruit, vegetable, and cereal) were studied by FT-Raman spectroscopy and thermogravimetry (TGA), respectively. 26927821 0 62 theme Proteins 80:87 arg1 Structure 37:45 Structure 37:45 Structure 37:45 Dietary Fiber-Induced Changes in the Structure and Thermal Properties of Gluten Proteins Studied by Fourier Transform-Raman Spectroscopy and Thermogravimetry. 26927821 0 62 theme Proteins 80:87 arg1 Properties 59:68 Thermal Properties 51:68 Thermal Properties 51:68 Dietary Fiber-Induced Changes in the Structure and Thermal Properties of Gluten Proteins Studied by Fourier Transform-Raman Spectroscopy and Thermogravimetry. 26927821 1 63 theme gluten 180:185 arg1 proteins 187:194 gluten proteins 180:194 gluten proteins 180:194 Interactions between gluten proteins and dietary fiber supplements at the stage of bread dough formation are crucial in the baking industry. 26927821 9 64 theme abnormal 1631:1638 arg1 folding 1640:1646 abnormal folding 1631:1646 abnormal folding 1631:1646 The results concerning structural changes suggested that the observed formation of hydrogen bonds in the β-structures can be connected with aggregation or abnormal folding. 26927821 4 65 theme gluten 609:614 arg1 proteins 616:623 gluten proteins 609:623 gluten proteins 609:623 Changes in the structure of gluten proteins and their thermal properties induced by seven commercial dietary fibers (fruit, vegetable, and cereal) were studied by FT-Raman spectroscopy and thermogravimetry (TGA), respectively. 26927821 8 66 theme bridges 1381:1387 arg1 conformation 1355:1366 conformation 1355:1366 conformation of disulfide bridges 1355:1387 Other changes observed in the gluten structure, concerning other β-structures, conformation of disulfide bridges, and aromatic amino acid microenvironment, depend on the fibers' chemical composition. 26927821 8 66 theme bridges 1381:1387 arg1 β-structures 1341:1352 other β-structures 1335:1352 other β-structures 1335:1352 Other changes observed in the gluten structure, concerning other β-structures, conformation of disulfide bridges, and aromatic amino acid microenvironment, depend on the fibers' chemical composition. 26927821 8 66 theme bridges 1381:1387 arg1 microenvironment 1414:1429 aromatic amino acid microenvironment 1394:1429 aromatic amino acid microenvironment 1394:1429 Other changes observed in the gluten structure, concerning other β-structures, conformation of disulfide bridges, and aromatic amino acid microenvironment, depend on the fibers' chemical composition. 26927821 4 67 from Changes 581:587 arg1 properties 643:652 their thermal properties 629:652 their thermal properties 629:652 Changes in the structure of gluten proteins and their thermal properties induced by seven commercial dietary fibers (fruit, vegetable, and cereal) were studied by FT-Raman spectroscopy and thermogravimetry (TGA), respectively. 26927821 4 67 from Changes 581:587 arg1 structure 596:604 the structure 592:604 the structure of gluten proteins 592:623 Changes in the structure of gluten proteins and their thermal properties induced by seven commercial dietary fibers (fruit, vegetable, and cereal) were studied by FT-Raman spectroscopy and thermogravimetry (TGA), respectively. 26927821 4 68 dep fibers 690:695 arg1 vegetable 705:713 vegetable 705:713 vegetable 705:713 Changes in the structure of gluten proteins and their thermal properties induced by seven commercial dietary fibers (fruit, vegetable, and cereal) were studied by FT-Raman spectroscopy and thermogravimetry (TGA), respectively. 26927821 4 68 dep fibers 690:695 arg1 cereal 720:725 cereal 720:725 cereal 720:725 Changes in the structure of gluten proteins and their thermal properties induced by seven commercial dietary fibers (fruit, vegetable, and cereal) were studied by FT-Raman spectroscopy and thermogravimetry (TGA), respectively. 26927821 4 68 dep fibers 690:695 arg1 fruit 698:702 fruit 698:702 fruit 698:702 Changes in the structure of gluten proteins and their thermal properties induced by seven commercial dietary fibers (fruit, vegetable, and cereal) were studied by FT-Raman spectroscopy and thermogravimetry (TGA), respectively. 26927821 6 69 theme obtained 985:992 arg1 results 994:1000 The obtained results 981:1000 The obtained results 981:1000 The obtained results revealed that all dietary fibers apart from oat caused similar changes in the secondary structure of gluten proteins. 26927821 11 70 theme gluten 1785:1790 arg1 network 1792:1798 a more complex and strong gluten network 1759:1798 a more complex and strong gluten network 1759:1798 Changes in weight loss indicated the formation of a more complex and strong gluten network. 26927821 0 71 theme Fiber-Induced 8:20 arg1 Changes 22:28 Dietary Fiber-Induced Changes 0:28 Dietary Fiber-Induced Changes in the Structure and Thermal Properties of Gluten Proteins 0:87 Dietary Fiber-Induced Changes in the Structure and Thermal Properties of Gluten Proteins Studied by Fourier Transform-Raman Spectroscopy and Thermogravimetry. 26927821 5 72 theme starch 888:893 arg1 blend 873:877 a blend 871:877 a blend of wheat starch and wheat gluten as well as the fiber, the content of which ranged from 3 to 18% w/w 871:978 For this aim the bread dough at 500 FU consistency was made of a blend of wheat starch and wheat gluten as well as the fiber, the content of which ranged from 3 to 18% w/w. 26927821 8 73 theme amino 1403:1407 arg1 microenvironment 1414:1429 aromatic amino acid microenvironment 1394:1429 aromatic amino acid microenvironment 1394:1429 Other changes observed in the gluten structure, concerning other β-structures, conformation of disulfide bridges, and aromatic amino acid microenvironment, depend on the fibers' chemical composition. 26927821 3 74 theme fiber 439:443 arg1 enrichment 445:454 The fiber enrichment 435:454 The fiber enrichment of bread 435:463 The fiber enrichment of bread causes a significant reduction in its quality, which is connected with changes in the structure of gluten proteins. 26927821 5 75 theme wheat 899:903 arg1 gluten 905:910 wheat gluten 899:910 wheat gluten 899:910 For this aim the bread dough at 500 FU consistency was made of a blend of wheat starch and wheat gluten as well as the fiber, the content of which ranged from 3 to 18% w/w. 26927821 3 76 theme significant 474:484 arg1 reduction 486:494 a significant reduction 472:494 a significant reduction 472:494 The fiber enrichment of bread causes a significant reduction in its quality, which is connected with changes in the structure of gluten proteins. 26927821 0 77 theme Transform-Raman 108:122 arg1 Spectroscopy 124:135 Fourier Transform-Raman Spectroscopy 100:135 Fourier Transform-Raman Spectroscopy 100:135 Dietary Fiber-Induced Changes in the Structure and Thermal Properties of Gluten Proteins Studied by Fourier Transform-Raman Spectroscopy and Thermogravimetry. 26927821 0 78 theme Thermal 51:57 arg1 Properties 59:68 Thermal Properties 51:68 Thermal Properties 51:68 Dietary Fiber-Induced Changes in the Structure and Thermal Properties of Gluten Proteins Studied by Fourier Transform-Raman Spectroscopy and Thermogravimetry. 26927821 0 79 dep Structure 37:45 arg1 the 33:35 the 33:35 the 33:35 Dietary Fiber-Induced Changes in the Structure and Thermal Properties of Gluten Proteins Studied by Fourier Transform-Raman Spectroscopy and Thermogravimetry. 26927821 7 80 dep β-sheets 1208:1215 arg1 cm 1232:1233 1614 and 1684 cm 1218:1233 1614 and 1684 cm(-1) 1218:1237 The most noticeable changes were observed in the regions connected with hydrogen-bonded β-sheets (1614 and 1684 cm(-1)) and β-turns (1640 and 1657 cm(-1)). 26927821 7 80 dep β-sheets 1208:1215 arg1 -1 1235:1236 -1 1235:1236 -1 1235:1236 The most noticeable changes were observed in the regions connected with hydrogen-bonded β-sheets (1614 and 1684 cm(-1)) and β-turns (1640 and 1657 cm(-1)). 26927821 1 81 theme dough 248:252 arg1 formation 254:262 bread dough formation 242:262 bread dough formation 242:262 Interactions between gluten proteins and dietary fiber supplements at the stage of bread dough formation are crucial in the baking industry. 26927821 5 82 theme bread 825:829 arg1 dough 831:835 the bread dough 821:835 the bread dough at 500 FU consistency 821:857 For this aim the bread dough at 500 FU consistency was made of a blend of wheat starch and wheat gluten as well as the fiber, the content of which ranged from 3 to 18% w/w. 26927821 2 83 theme positive 401:408 arg1 effects 410:416 positive effects 401:416 positive effects 401:416 The dietary fiber additives are regarded as a source of polysaccharides and antioxidants, which have positive effects on human health. 26927821 4 84 theme proteins 616:623 arg1 properties 643:652 their thermal properties 629:652 their thermal properties 629:652 Changes in the structure of gluten proteins and their thermal properties induced by seven commercial dietary fibers (fruit, vegetable, and cereal) were studied by FT-Raman spectroscopy and thermogravimetry (TGA), respectively. 26927821 4 84 theme proteins 616:623 arg1 structure 596:604 the structure 592:604 the structure of gluten proteins 592:623 Changes in the structure of gluten proteins and their thermal properties induced by seven commercial dietary fibers (fruit, vegetable, and cereal) were studied by FT-Raman spectroscopy and thermogravimetry (TGA), respectively. 26927821 8 85 theme Other 1276:1280 arg1 changes 1282:1288 Other changes 1276:1288 Other changes 1276:1288 Other changes observed in the gluten structure, concerning other β-structures, conformation of disulfide bridges, and aromatic amino acid microenvironment, depend on the fibers' chemical composition. 26927821 2 86 theme antioxidants 376:387 arg1 source 346:351 a source 344:351 a source 344:351 The dietary fiber additives are regarded as a source of polysaccharides and antioxidants, which have positive effects on human health. 26927821 2 86 theme antioxidants 376:387 arg1 additives 318:326 The dietary fiber additives 300:326 The dietary fiber additives 300:326 The dietary fiber additives are regarded as a source of polysaccharides and antioxidants, which have positive effects on human health. 26559702 0 0 theme Higher 81:86 arg1 Basidiomycetes 88:101 Higher Basidiomycetes 81:101 Higher Basidiomycetes 81:101 Optimization of Liquid Fermentation Medium for Production of Inonotus sanghuang (Higher Basidiomycetes) Mycelia and Evaluation of their Mycochemical Contents and Antioxidant Activities. 26559702 1 1 theme traditional 248:258 arg1 medicine 268:275 traditional Chinese medicine 248:275 traditional Chinese medicine 248:275 Inonotus sanghuang, an authentic "Sanghuang" mushroom used in traditional Chinese medicine, is known to possess important pharmacological activities. 26559702 2 2 theme cultivation 482:492 arg1 effects 461:467 the effects 457:467 the effects of two-stage cultivation (shake and static) on the yield of total flavonoids, total phenolics, and polysaccharides, as well as the antioxidant activities of I. sanghuang mycelial extracts (ISME) 457:662 In this study, we aimed to optimize the liquid fermentation medium for I. sanghuang mycelial production and to determine the effects of two-stage cultivation (shake and static) on the yield of total flavonoids, total phenolics, and polysaccharides, as well as the antioxidant activities of I. sanghuang mycelial extracts (ISME). 26559702 1 3 theme Chinese 260:266 arg1 medicine 268:275 traditional Chinese medicine 248:275 traditional Chinese medicine 248:275 Inonotus sanghuang, an authentic "Sanghuang" mushroom used in traditional Chinese medicine, is known to possess important pharmacological activities. 26559702 2 4 theme polysaccharides 568:582 arg1 yield 520:524 the yield 516:524 the yield of total flavonoids, total phenolics, and polysaccharides, as well as the antioxidant activities of I. sanghuang mycelial extracts (ISME) 516:662 In this study, we aimed to optimize the liquid fermentation medium for I. sanghuang mycelial production and to determine the effects of two-stage cultivation (shake and static) on the yield of total flavonoids, total phenolics, and polysaccharides, as well as the antioxidant activities of I. sanghuang mycelial extracts (ISME). 26559702 2 5 theme I. 626:627 arg1 activities 612:621 the antioxidant activities 596:621 the antioxidant activities of I. sanghuang mycelial extracts (ISME) 596:662 In this study, we aimed to optimize the liquid fermentation medium for I. sanghuang mycelial production and to determine the effects of two-stage cultivation (shake and static) on the yield of total flavonoids, total phenolics, and polysaccharides, as well as the antioxidant activities of I. sanghuang mycelial extracts (ISME). 26559702 2 5 theme I. 626:627 arg1 flavonoids 535:544 total flavonoids 529:544 total flavonoids 529:544 In this study, we aimed to optimize the liquid fermentation medium for I. sanghuang mycelial production and to determine the effects of two-stage cultivation (shake and static) on the yield of total flavonoids, total phenolics, and polysaccharides, as well as the antioxidant activities of I. sanghuang mycelial extracts (ISME). 26559702 2 5 theme I. 626:627 arg1 phenolics 553:561 total phenolics 547:561 total phenolics 547:561 In this study, we aimed to optimize the liquid fermentation medium for I. sanghuang mycelial production and to determine the effects of two-stage cultivation (shake and static) on the yield of total flavonoids, total phenolics, and polysaccharides, as well as the antioxidant activities of I. sanghuang mycelial extracts (ISME). 26559702 2 5 theme I. 626:627 arg1 polysaccharides 568:582 polysaccharides 568:582 polysaccharides 568:582 In this study, we aimed to optimize the liquid fermentation medium for I. sanghuang mycelial production and to determine the effects of two-stage cultivation (shake and static) on the yield of total flavonoids, total phenolics, and polysaccharides, as well as the antioxidant activities of I. sanghuang mycelial extracts (ISME). 26559702 1 6 contain possess 290:296 arg1 sanghuang 195:203 Inonotus sanghuang 186:203 Inonotus sanghuang 186:203 Inonotus sanghuang, an authentic "Sanghuang" mushroom used in traditional Chinese medicine, is known to possess important pharmacological activities. 26559702 1 6 contain possess 290:296 arg2 activities 324:333 important pharmacological activities 298:333 important pharmacological activities 298:333 Inonotus sanghuang, an authentic "Sanghuang" mushroom used in traditional Chinese medicine, is known to possess important pharmacological activities. 26559702 1 6 contain possess 290:296 arg1 mushroom 231:238 an authentic "Sanghuang" mushroom 206:238 an authentic "Sanghuang" mushroom used in traditional Chinese medicine 206:275 Inonotus sanghuang, an authentic "Sanghuang" mushroom used in traditional Chinese medicine, is known to possess important pharmacological activities. 26559702 4 7 theme phenolics 983:991 arg1 contents 944:951 contents 944:951 contents of total flavonoids and total phenolics in mycelia 944:1002 The results of two-stage cultivation showed that contents of total flavonoids and total phenolics in mycelia increased by 37.92% and 77.27%, respectively. 26559702 5 8 theme polysaccharide 1069:1082 arg1 contents 1084:1091 irregular polysaccharide contents 1059:1091 irregular polysaccharide contents 1059:1091 However, irregular polysaccharide contents were noted throughout the experimental period. 26559702 2 9 from effects 461:467 arg1 yield 520:524 the yield 516:524 the yield of total flavonoids, total phenolics, and polysaccharides, as well as the antioxidant activities of I. sanghuang mycelial extracts (ISME) 516:662 In this study, we aimed to optimize the liquid fermentation medium for I. sanghuang mycelial production and to determine the effects of two-stage cultivation (shake and static) on the yield of total flavonoids, total phenolics, and polysaccharides, as well as the antioxidant activities of I. sanghuang mycelial extracts (ISME). 26559702 3 10 theme mycelial 827:834 arg1 biomasses 836:844 experimental optimal mycelial biomasses 806:844 experimental optimal mycelial biomasses 806:844 Under an optimized medium composition (38.96 g/L of corn flour, 4.15 g/L of yeast extract, 20.55 g/L of bran and pH 6.39), the predicted and experimental optimal mycelial biomasses were 17.60 g/L and 18.33±0.86 g/L, respectively. 26559702 3 11 theme optimal 819:825 arg1 biomasses 836:844 experimental optimal mycelial biomasses 806:844 experimental optimal mycelial biomasses 806:844 Under an optimized medium composition (38.96 g/L of corn flour, 4.15 g/L of yeast extract, 20.55 g/L of bran and pH 6.39), the predicted and experimental optimal mycelial biomasses were 17.60 g/L and 18.33±0.86 g/L, respectively. 26559702 2 12 theme antioxidant 600:610 arg1 activities 612:621 the antioxidant activities 596:621 the antioxidant activities of I. sanghuang mycelial extracts (ISME) 596:662 In this study, we aimed to optimize the liquid fermentation medium for I. sanghuang mycelial production and to determine the effects of two-stage cultivation (shake and static) on the yield of total flavonoids, total phenolics, and polysaccharides, as well as the antioxidant activities of I. sanghuang mycelial extracts (ISME). 26559702 2 13 theme activities 612:621 arg1 yield 520:524 the yield 516:524 the yield of total flavonoids, total phenolics, and polysaccharides, as well as the antioxidant activities of I. sanghuang mycelial extracts (ISME) 516:662 In this study, we aimed to optimize the liquid fermentation medium for I. sanghuang mycelial production and to determine the effects of two-stage cultivation (shake and static) on the yield of total flavonoids, total phenolics, and polysaccharides, as well as the antioxidant activities of I. sanghuang mycelial extracts (ISME). 26559702 2 14 dep cultivation 482:492 arg1 shake 495:499 shake 495:499 shake 495:499 In this study, we aimed to optimize the liquid fermentation medium for I. sanghuang mycelial production and to determine the effects of two-stage cultivation (shake and static) on the yield of total flavonoids, total phenolics, and polysaccharides, as well as the antioxidant activities of I. sanghuang mycelial extracts (ISME). 26559702 2 14 dep cultivation 482:492 arg1 static 505:510 static 505:510 static 505:510 In this study, we aimed to optimize the liquid fermentation medium for I. sanghuang mycelial production and to determine the effects of two-stage cultivation (shake and static) on the yield of total flavonoids, total phenolics, and polysaccharides, as well as the antioxidant activities of I. sanghuang mycelial extracts (ISME). 26559702 0 15 theme Mycelia 104:110 arg1 Evaluation 116:125 Evaluation 116:125 Evaluation of their Mycochemical Contents and Antioxidant Activities 116:183 Optimization of Liquid Fermentation Medium for Production of Inonotus sanghuang (Higher Basidiomycetes) Mycelia and Evaluation of their Mycochemical Contents and Antioxidant Activities. 26559702 0 15 theme Mycelia 104:110 arg1 Production 47:56 Production 47:56 Production of Inonotus sanghuang (Higher Basidiomycetes) Mycelia 47:110 Optimization of Liquid Fermentation Medium for Production of Inonotus sanghuang (Higher Basidiomycetes) Mycelia and Evaluation of their Mycochemical Contents and Antioxidant Activities. 26559702 3 16 theme optimized 674:682 arg1 composition 691:701 an optimized medium composition 671:701 an optimized medium composition (38.96 g/L of corn flour, 4.15 g/L of yeast extract, 20.55 g/L of bran and pH 6.39) 671:785 Under an optimized medium composition (38.96 g/L of corn flour, 4.15 g/L of yeast extract, 20.55 g/L of bran and pH 6.39), the predicted and experimental optimal mycelial biomasses were 17.60 g/L and 18.33±0.86 g/L, respectively. 26559702 4 17 theme cultivation 920:930 arg1 results 899:905 The results 895:905 The results of two-stage cultivation 895:930 The results of two-stage cultivation showed that contents of total flavonoids and total phenolics in mycelia increased by 37.92% and 77.27%, respectively. 26559702 3 18 theme experimental 806:817 arg1 biomasses 836:844 experimental optimal mycelial biomasses 806:844 experimental optimal mycelial biomasses 806:844 Under an optimized medium composition (38.96 g/L of corn flour, 4.15 g/L of yeast extract, 20.55 g/L of bran and pH 6.39), the predicted and experimental optimal mycelial biomasses were 17.60 g/L and 18.33±0.86 g/L, respectively. 26559702 1 19 theme Inonotus 186:193 arg1 sanghuang 195:203 Inonotus sanghuang 186:203 Inonotus sanghuang 186:203 Inonotus sanghuang, an authentic "Sanghuang" mushroom used in traditional Chinese medicine, is known to possess important pharmacological activities. 26559702 1 19 theme Inonotus 186:193 arg1 mushroom 231:238 an authentic "Sanghuang" mushroom 206:238 an authentic "Sanghuang" mushroom used in traditional Chinese medicine 206:275 Inonotus sanghuang, an authentic "Sanghuang" mushroom used in traditional Chinese medicine, is known to possess important pharmacological activities. 26559702 3 20 theme medium 684:689 arg1 composition 691:701 an optimized medium composition 671:701 an optimized medium composition (38.96 g/L of corn flour, 4.15 g/L of yeast extract, 20.55 g/L of bran and pH 6.39) 671:785 Under an optimized medium composition (38.96 g/L of corn flour, 4.15 g/L of yeast extract, 20.55 g/L of bran and pH 6.39), the predicted and experimental optimal mycelial biomasses were 17.60 g/L and 18.33±0.86 g/L, respectively. 26559702 6 21 theme good 1186:1189 arg1 activity 1215:1222 good free-radical scavenging activity 1186:1222 good free-radical scavenging activity 1186:1222 Antioxidant assays showed that ISME possessed good free-radical scavenging activity, which is mainly contributed by polyphenolic-type metabolites. 26559702 2 22 theme phenolics 553:561 arg1 yield 520:524 the yield 516:524 the yield of total flavonoids, total phenolics, and polysaccharides, as well as the antioxidant activities of I. sanghuang mycelial extracts (ISME) 516:662 In this study, we aimed to optimize the liquid fermentation medium for I. sanghuang mycelial production and to determine the effects of two-stage cultivation (shake and static) on the yield of total flavonoids, total phenolics, and polysaccharides, as well as the antioxidant activities of I. sanghuang mycelial extracts (ISME). 26559702 2 23 theme liquid 376:381 arg1 medium 396:401 the liquid fermentation medium 372:401 the liquid fermentation medium for I. sanghuang mycelial production and to determine the effects of two-stage cultivation (shake and static) on the yield of total flavonoids, total phenolics, and polysaccharides, as well as the antioxidant activities of I. sanghuang mycelial extracts (ISME) 372:662 In this study, we aimed to optimize the liquid fermentation medium for I. sanghuang mycelial production and to determine the effects of two-stage cultivation (shake and static) on the yield of total flavonoids, total phenolics, and polysaccharides, as well as the antioxidant activities of I. sanghuang mycelial extracts (ISME). 26559702 5 24 theme experimental 1119:1130 arg1 period 1132:1137 the experimental period 1115:1137 the experimental period 1115:1137 However, irregular polysaccharide contents were noted throughout the experimental period. 26559702 3 25 dep composition 691:701 arg1 g/L 762:764 20.55 g/L 756:764 20.55 g/L of bran 756:772 Under an optimized medium composition (38.96 g/L of corn flour, 4.15 g/L of yeast extract, 20.55 g/L of bran and pH 6.39), the predicted and experimental optimal mycelial biomasses were 17.60 g/L and 18.33±0.86 g/L, respectively. 26559702 3 25 dep composition 691:701 arg1 g/L 734:736 4.15 g/L 729:736 4.15 g/L of yeast extract 729:753 Under an optimized medium composition (38.96 g/L of corn flour, 4.15 g/L of yeast extract, 20.55 g/L of bran and pH 6.39), the predicted and experimental optimal mycelial biomasses were 17.60 g/L and 18.33±0.86 g/L, respectively. 26559702 3 25 dep composition 691:701 arg1 g/L 710:712 38.96 g/L 704:712 38.96 g/L of corn flour 704:726 Under an optimized medium composition (38.96 g/L of corn flour, 4.15 g/L of yeast extract, 20.55 g/L of bran and pH 6.39), the predicted and experimental optimal mycelial biomasses were 17.60 g/L and 18.33±0.86 g/L, respectively. 26559702 3 25 dep composition 691:701 arg1 pH 778:779 pH 6.39 778:784 pH 6.39 778:784 Under an optimized medium composition (38.96 g/L of corn flour, 4.15 g/L of yeast extract, 20.55 g/L of bran and pH 6.39), the predicted and experimental optimal mycelial biomasses were 17.60 g/L and 18.33±0.86 g/L, respectively. 26559702 6 26 theme scavenging 1204:1213 arg1 activity 1215:1222 good free-radical scavenging activity 1186:1222 good free-radical scavenging activity 1186:1222 Antioxidant assays showed that ISME possessed good free-radical scavenging activity, which is mainly contributed by polyphenolic-type metabolites. 26559702 6 27 contain possessed 1176:1184 arg2 activity 1215:1222 good free-radical scavenging activity 1186:1222 good free-radical scavenging activity 1186:1222 Antioxidant assays showed that ISME possessed good free-radical scavenging activity, which is mainly contributed by polyphenolic-type metabolites. 26559702 6 27 contain possessed 1176:1184 arg1 ISME 1171:1174 ISME 1171:1174 ISME 1171:1174 Antioxidant assays showed that ISME possessed good free-radical scavenging activity, which is mainly contributed by polyphenolic-type metabolites. 26559702 0 28 theme Fermentation 23:34 arg1 Medium 36:41 Liquid Fermentation Medium 16:41 Liquid Fermentation Medium 16:41 Optimization of Liquid Fermentation Medium for Production of Inonotus sanghuang (Higher Basidiomycetes) Mycelia and Evaluation of their Mycochemical Contents and Antioxidant Activities. 26559702 3 29 theme corn 717:720 arg1 flour 722:726 corn flour 717:726 corn flour 717:726 Under an optimized medium composition (38.96 g/L of corn flour, 4.15 g/L of yeast extract, 20.55 g/L of bran and pH 6.39), the predicted and experimental optimal mycelial biomasses were 17.60 g/L and 18.33±0.86 g/L, respectively. 26559702 2 30 theme flavonoids 535:544 arg1 yield 520:524 the yield 516:524 the yield of total flavonoids, total phenolics, and polysaccharides, as well as the antioxidant activities of I. sanghuang mycelial extracts (ISME) 516:662 In this study, we aimed to optimize the liquid fermentation medium for I. sanghuang mycelial production and to determine the effects of two-stage cultivation (shake and static) on the yield of total flavonoids, total phenolics, and polysaccharides, as well as the antioxidant activities of I. sanghuang mycelial extracts (ISME). 26559702 2 31 theme mycelial 639:646 arg1 extracts 648:655 mycelial extracts 639:655 mycelial extracts (ISME) 639:662 In this study, we aimed to optimize the liquid fermentation medium for I. sanghuang mycelial production and to determine the effects of two-stage cultivation (shake and static) on the yield of total flavonoids, total phenolics, and polysaccharides, as well as the antioxidant activities of I. sanghuang mycelial extracts (ISME). 26559702 2 31 theme mycelial 639:646 arg1 ISME 658:661 ISME 658:661 ISME 658:661 In this study, we aimed to optimize the liquid fermentation medium for I. sanghuang mycelial production and to determine the effects of two-stage cultivation (shake and static) on the yield of total flavonoids, total phenolics, and polysaccharides, as well as the antioxidant activities of I. sanghuang mycelial extracts (ISME). 26559702 0 32 dep sanghuang 70:78 arg1 Basidiomycetes 88:101 Higher Basidiomycetes 81:101 Higher Basidiomycetes 81:101 Optimization of Liquid Fermentation Medium for Production of Inonotus sanghuang (Higher Basidiomycetes) Mycelia and Evaluation of their Mycochemical Contents and Antioxidant Activities. 26559702 2 33 theme mycelial 420:427 arg1 production 429:438 mycelial production 420:438 mycelial production 420:438 In this study, we aimed to optimize the liquid fermentation medium for I. sanghuang mycelial production and to determine the effects of two-stage cultivation (shake and static) on the yield of total flavonoids, total phenolics, and polysaccharides, as well as the antioxidant activities of I. sanghuang mycelial extracts (ISME). 26559702 0 34 theme Liquid 16:21 arg1 Medium 36:41 Liquid Fermentation Medium 16:41 Liquid Fermentation Medium 16:41 Optimization of Liquid Fermentation Medium for Production of Inonotus sanghuang (Higher Basidiomycetes) Mycelia and Evaluation of their Mycochemical Contents and Antioxidant Activities. 26559702 2 35 theme total 529:533 arg1 flavonoids 535:544 total flavonoids 529:544 total flavonoids 529:544 In this study, we aimed to optimize the liquid fermentation medium for I. sanghuang mycelial production and to determine the effects of two-stage cultivation (shake and static) on the yield of total flavonoids, total phenolics, and polysaccharides, as well as the antioxidant activities of I. sanghuang mycelial extracts (ISME). 26559702 1 36 theme authentic 209:217 arg1 sanghuang 195:203 Inonotus sanghuang 186:203 Inonotus sanghuang 186:203 Inonotus sanghuang, an authentic "Sanghuang" mushroom used in traditional Chinese medicine, is known to possess important pharmacological activities. 26559702 1 36 theme authentic 209:217 arg1 mushroom 231:238 an authentic "Sanghuang" mushroom 206:238 an authentic "Sanghuang" mushroom used in traditional Chinese medicine 206:275 Inonotus sanghuang, an authentic "Sanghuang" mushroom used in traditional Chinese medicine, is known to possess important pharmacological activities. 26559702 2 37 theme two-stage 472:480 arg1 cultivation 482:492 two-stage cultivation 472:492 two-stage cultivation (shake and static) 472:511 In this study, we aimed to optimize the liquid fermentation medium for I. sanghuang mycelial production and to determine the effects of two-stage cultivation (shake and static) on the yield of total flavonoids, total phenolics, and polysaccharides, as well as the antioxidant activities of I. sanghuang mycelial extracts (ISME). 26559702 4 38 from contents 944:951 arg1 mycelia 996:1002 mycelia 996:1002 mycelia 996:1002 The results of two-stage cultivation showed that contents of total flavonoids and total phenolics in mycelia increased by 37.92% and 77.27%, respectively. 26559702 0 39 theme Mycochemical 136:147 arg1 Contents 149:156 their Mycochemical Contents 130:156 their Mycochemical Contents 130:156 Optimization of Liquid Fermentation Medium for Production of Inonotus sanghuang (Higher Basidiomycetes) Mycelia and Evaluation of their Mycochemical Contents and Antioxidant Activities. 26559702 0 40 theme Medium 36:41 arg1 Optimization 0:11 Optimization 0:11 Optimization of Liquid Fermentation Medium for Production of Inonotus sanghuang (Higher Basidiomycetes) Mycelia and Evaluation of their Mycochemical Contents and Antioxidant Activities. 0:184 Optimization of Liquid Fermentation Medium for Production of Inonotus sanghuang (Higher Basidiomycetes) Mycelia and Evaluation of their Mycochemical Contents and Antioxidant Activities. 26559702 1 41 theme important 298:306 arg1 activities 324:333 important pharmacological activities 298:333 important pharmacological activities 298:333 Inonotus sanghuang, an authentic "Sanghuang" mushroom used in traditional Chinese medicine, is known to possess important pharmacological activities. 26559702 3 42 theme bran 769:772 arg1 pH 778:779 pH 6.39 778:784 pH 6.39 778:784 Under an optimized medium composition (38.96 g/L of corn flour, 4.15 g/L of yeast extract, 20.55 g/L of bran and pH 6.39), the predicted and experimental optimal mycelial biomasses were 17.60 g/L and 18.33±0.86 g/L, respectively. 26559702 3 42 theme bran 769:772 arg1 g/L 762:764 20.55 g/L 756:764 20.55 g/L of bran 756:772 Under an optimized medium composition (38.96 g/L of corn flour, 4.15 g/L of yeast extract, 20.55 g/L of bran and pH 6.39), the predicted and experimental optimal mycelial biomasses were 17.60 g/L and 18.33±0.86 g/L, respectively. 26559702 3 42 theme bran 769:772 arg1 g/L 710:712 38.96 g/L 704:712 38.96 g/L of corn flour 704:726 Under an optimized medium composition (38.96 g/L of corn flour, 4.15 g/L of yeast extract, 20.55 g/L of bran and pH 6.39), the predicted and experimental optimal mycelial biomasses were 17.60 g/L and 18.33±0.86 g/L, respectively. 26559702 3 42 theme bran 769:772 arg1 g/L 734:736 4.15 g/L 729:736 4.15 g/L of yeast extract 729:753 Under an optimized medium composition (38.96 g/L of corn flour, 4.15 g/L of yeast extract, 20.55 g/L of bran and pH 6.39), the predicted and experimental optimal mycelial biomasses were 17.60 g/L and 18.33±0.86 g/L, respectively. 26559702 4 43 theme flavonoids 962:971 arg1 contents 944:951 contents 944:951 contents of total flavonoids and total phenolics in mycelia 944:1002 The results of two-stage cultivation showed that contents of total flavonoids and total phenolics in mycelia increased by 37.92% and 77.27%, respectively. 26559702 1 44 theme Sanghuang 220:228 arg1 sanghuang 195:203 Inonotus sanghuang 186:203 Inonotus sanghuang 186:203 Inonotus sanghuang, an authentic "Sanghuang" mushroom used in traditional Chinese medicine, is known to possess important pharmacological activities. 26559702 1 44 theme Sanghuang 220:228 arg1 mushroom 231:238 an authentic "Sanghuang" mushroom 206:238 an authentic "Sanghuang" mushroom used in traditional Chinese medicine 206:275 Inonotus sanghuang, an authentic "Sanghuang" mushroom used in traditional Chinese medicine, is known to possess important pharmacological activities. 26559702 1 45 theme pharmacological 308:322 arg1 activities 324:333 important pharmacological activities 298:333 important pharmacological activities 298:333 Inonotus sanghuang, an authentic "Sanghuang" mushroom used in traditional Chinese medicine, is known to possess important pharmacological activities. 26559702 6 46 theme polyphenolic-type 1256:1272 arg1 metabolites 1274:1284 polyphenolic-type metabolites 1256:1284 polyphenolic-type metabolites 1256:1284 Antioxidant assays showed that ISME possessed good free-radical scavenging activity, which is mainly contributed by polyphenolic-type metabolites. 26559702 2 47 theme total 547:551 arg1 phenolics 553:561 total phenolics 547:561 total phenolics 547:561 In this study, we aimed to optimize the liquid fermentation medium for I. sanghuang mycelial production and to determine the effects of two-stage cultivation (shake and static) on the yield of total flavonoids, total phenolics, and polysaccharides, as well as the antioxidant activities of I. sanghuang mycelial extracts (ISME). 26559702 3 48 theme flour 722:726 arg1 pH 778:779 pH 6.39 778:784 pH 6.39 778:784 Under an optimized medium composition (38.96 g/L of corn flour, 4.15 g/L of yeast extract, 20.55 g/L of bran and pH 6.39), the predicted and experimental optimal mycelial biomasses were 17.60 g/L and 18.33±0.86 g/L, respectively. 26559702 3 48 theme flour 722:726 arg1 g/L 762:764 20.55 g/L 756:764 20.55 g/L of bran 756:772 Under an optimized medium composition (38.96 g/L of corn flour, 4.15 g/L of yeast extract, 20.55 g/L of bran and pH 6.39), the predicted and experimental optimal mycelial biomasses were 17.60 g/L and 18.33±0.86 g/L, respectively. 26559702 3 48 theme flour 722:726 arg1 g/L 710:712 38.96 g/L 704:712 38.96 g/L of corn flour 704:726 Under an optimized medium composition (38.96 g/L of corn flour, 4.15 g/L of yeast extract, 20.55 g/L of bran and pH 6.39), the predicted and experimental optimal mycelial biomasses were 17.60 g/L and 18.33±0.86 g/L, respectively. 26559702 3 48 theme flour 722:726 arg1 g/L 734:736 4.15 g/L 729:736 4.15 g/L of yeast extract 729:753 Under an optimized medium composition (38.96 g/L of corn flour, 4.15 g/L of yeast extract, 20.55 g/L of bran and pH 6.39), the predicted and experimental optimal mycelial biomasses were 17.60 g/L and 18.33±0.86 g/L, respectively. 26559702 0 49 theme Contents 149:156 arg1 Evaluation 116:125 Evaluation 116:125 Evaluation of their Mycochemical Contents and Antioxidant Activities 116:183 Optimization of Liquid Fermentation Medium for Production of Inonotus sanghuang (Higher Basidiomycetes) Mycelia and Evaluation of their Mycochemical Contents and Antioxidant Activities. 26559702 0 49 theme Contents 149:156 arg1 Production 47:56 Production 47:56 Production of Inonotus sanghuang (Higher Basidiomycetes) Mycelia 47:110 Optimization of Liquid Fermentation Medium for Production of Inonotus sanghuang (Higher Basidiomycetes) Mycelia and Evaluation of their Mycochemical Contents and Antioxidant Activities. 26559702 6 50 theme free-radical 1191:1202 arg1 activity 1215:1222 good free-radical scavenging activity 1186:1222 good free-radical scavenging activity 1186:1222 Antioxidant assays showed that ISME possessed good free-radical scavenging activity, which is mainly contributed by polyphenolic-type metabolites. 26559702 0 51 theme Activities 174:183 arg1 Evaluation 116:125 Evaluation 116:125 Evaluation of their Mycochemical Contents and Antioxidant Activities 116:183 Optimization of Liquid Fermentation Medium for Production of Inonotus sanghuang (Higher Basidiomycetes) Mycelia and Evaluation of their Mycochemical Contents and Antioxidant Activities. 26559702 0 51 theme Activities 174:183 arg1 Production 47:56 Production 47:56 Production of Inonotus sanghuang (Higher Basidiomycetes) Mycelia 47:110 Optimization of Liquid Fermentation Medium for Production of Inonotus sanghuang (Higher Basidiomycetes) Mycelia and Evaluation of their Mycochemical Contents and Antioxidant Activities. 26559702 6 52 theme Antioxidant 1140:1150 arg1 assays 1152:1157 Antioxidant assays 1140:1157 Antioxidant assays 1140:1157 Antioxidant assays showed that ISME possessed good free-radical scavenging activity, which is mainly contributed by polyphenolic-type metabolites. 26559702 4 53 theme two-stage 910:918 arg1 cultivation 920:930 two-stage cultivation 910:930 two-stage cultivation 910:930 The results of two-stage cultivation showed that contents of total flavonoids and total phenolics in mycelia increased by 37.92% and 77.27%, respectively. 26559702 1 54 theme " 229:229 arg1 sanghuang 195:203 Inonotus sanghuang 186:203 Inonotus sanghuang 186:203 Inonotus sanghuang, an authentic "Sanghuang" mushroom used in traditional Chinese medicine, is known to possess important pharmacological activities. 26559702 1 54 theme " 229:229 arg1 mushroom 231:238 an authentic "Sanghuang" mushroom 206:238 an authentic "Sanghuang" mushroom used in traditional Chinese medicine 206:275 Inonotus sanghuang, an authentic "Sanghuang" mushroom used in traditional Chinese medicine, is known to possess important pharmacological activities. 26559702 0 55 theme Antioxidant 162:172 arg1 Activities 174:183 Antioxidant Activities 162:183 Antioxidant Activities 162:183 Optimization of Liquid Fermentation Medium for Production of Inonotus sanghuang (Higher Basidiomycetes) Mycelia and Evaluation of their Mycochemical Contents and Antioxidant Activities. 26559702 0 56 theme sanghuang 70:78 arg1 Mycelia 104:110 Inonotus sanghuang (Higher Basidiomycetes) Mycelia 61:110 Inonotus sanghuang (Higher Basidiomycetes) Mycelia 61:110 Optimization of Liquid Fermentation Medium for Production of Inonotus sanghuang (Higher Basidiomycetes) Mycelia and Evaluation of their Mycochemical Contents and Antioxidant Activities. 26559702 2 57 theme fermentation 383:394 arg1 medium 396:401 the liquid fermentation medium 372:401 the liquid fermentation medium for I. sanghuang mycelial production and to determine the effects of two-stage cultivation (shake and static) on the yield of total flavonoids, total phenolics, and polysaccharides, as well as the antioxidant activities of I. sanghuang mycelial extracts (ISME) 372:662 In this study, we aimed to optimize the liquid fermentation medium for I. sanghuang mycelial production and to determine the effects of two-stage cultivation (shake and static) on the yield of total flavonoids, total phenolics, and polysaccharides, as well as the antioxidant activities of I. sanghuang mycelial extracts (ISME). 26559702 5 58 theme irregular 1059:1067 arg1 contents 1084:1091 irregular polysaccharide contents 1059:1091 irregular polysaccharide contents 1059:1091 However, irregular polysaccharide contents were noted throughout the experimental period. 26559702 4 59 theme total 956:960 arg1 flavonoids 962:971 total flavonoids 956:971 total flavonoids 956:971 The results of two-stage cultivation showed that contents of total flavonoids and total phenolics in mycelia increased by 37.92% and 77.27%, respectively. 26559702 3 60 theme extract 747:753 arg1 pH 778:779 pH 6.39 778:784 pH 6.39 778:784 Under an optimized medium composition (38.96 g/L of corn flour, 4.15 g/L of yeast extract, 20.55 g/L of bran and pH 6.39), the predicted and experimental optimal mycelial biomasses were 17.60 g/L and 18.33±0.86 g/L, respectively. 26559702 3 60 theme extract 747:753 arg1 g/L 762:764 20.55 g/L 756:764 20.55 g/L of bran 756:772 Under an optimized medium composition (38.96 g/L of corn flour, 4.15 g/L of yeast extract, 20.55 g/L of bran and pH 6.39), the predicted and experimental optimal mycelial biomasses were 17.60 g/L and 18.33±0.86 g/L, respectively. 26559702 3 60 theme extract 747:753 arg1 g/L 710:712 38.96 g/L 704:712 38.96 g/L of corn flour 704:726 Under an optimized medium composition (38.96 g/L of corn flour, 4.15 g/L of yeast extract, 20.55 g/L of bran and pH 6.39), the predicted and experimental optimal mycelial biomasses were 17.60 g/L and 18.33±0.86 g/L, respectively. 26559702 3 60 theme extract 747:753 arg1 g/L 734:736 4.15 g/L 729:736 4.15 g/L of yeast extract 729:753 Under an optimized medium composition (38.96 g/L of corn flour, 4.15 g/L of yeast extract, 20.55 g/L of bran and pH 6.39), the predicted and experimental optimal mycelial biomasses were 17.60 g/L and 18.33±0.86 g/L, respectively. 26559702 4 61 theme total 977:981 arg1 phenolics 983:991 total phenolics 977:991 total phenolics 977:991 The results of two-stage cultivation showed that contents of total flavonoids and total phenolics in mycelia increased by 37.92% and 77.27%, respectively. 26559702 3 62 theme yeast 741:745 arg1 extract 747:753 yeast extract 741:753 yeast extract 741:753 Under an optimized medium composition (38.96 g/L of corn flour, 4.15 g/L of yeast extract, 20.55 g/L of bran and pH 6.39), the predicted and experimental optimal mycelial biomasses were 17.60 g/L and 18.33±0.86 g/L, respectively. 28720961 5 0 theme soluble 705:711 arg1 carbohydrates 713:725 soluble carbohydrates 705:725 soluble carbohydrates 705:725 The contents of soluble carbohydrates, digestible starch, resistant starch and cellulose in the seeds were determined. 28720961 6 1 theme carbohydrate-degrading 855:876 arg1 enzymes 878:884 carbohydrate-degrading enzymes 855:884 carbohydrate-degrading enzymes 855:884 The radial diffusion method was used to detect carbohydrate-degrading enzymes in the seed extracts. 28720961 6 2 theme diffusion 819:827 arg1 method 829:834 The radial diffusion method 808:834 The radial diffusion method 808:834 The radial diffusion method was used to detect carbohydrate-degrading enzymes in the seed extracts. 28720961 3 3 theme carbohydrate 472:483 arg1 composition 485:495 the seed carbohydrate composition 463:495 the seed carbohydrate composition 463:495 The feed values of fruit seeds can be improved through germination, which involves the mobilization of nutrients through seed enzymes and alters the seed carbohydrate composition. 28720961 0 4 theme carbohydrate 72:83 arg1 changes 85:91 germination-induced carbohydrate changes 52:91 germination-induced carbohydrate changes 52:91 Valorizing guava (Psidium guajava L.) seeds through germination-induced carbohydrate changes. 28720961 9 5 theme soluble 1225:1231 arg1 contents 1246:1253 the soluble carbohydrate contents 1221:1253 the soluble carbohydrate contents in red beans and guava seeds 1221:1282 The starch contents of all the seeds decreased, but the soluble carbohydrate contents in red beans and guava seeds increased significantly by the end of germination, suggesting the transient oversupply of reserve metabolites. 28720961 5 6 from contents 693:700 arg1 seeds 785:789 the seeds 781:789 the seeds 781:789 The contents of soluble carbohydrates, digestible starch, resistant starch and cellulose in the seeds were determined. 28720961 1 7 theme guava 145:149 arg1 industry 162:169 the guava processing industry 141:169 the guava processing industry 141:169 Guava seeds are produced as a waste product by the guava processing industry. 28720961 6 8 used used 840:843 arg2 method 829:834 The radial diffusion method 808:834 The radial diffusion method 808:834 The radial diffusion method was used to detect carbohydrate-degrading enzymes in the seed extracts. 28720961 9 9 theme transient 1350:1358 arg1 oversupply 1360:1369 the transient oversupply 1346:1369 the transient oversupply of reserve metabolites 1346:1392 The starch contents of all the seeds decreased, but the soluble carbohydrate contents in red beans and guava seeds increased significantly by the end of germination, suggesting the transient oversupply of reserve metabolites. 28720961 4 10 from seeds 566:570 arg1 changes 502:508 The changes 498:508 The changes of selected carbohydrates in guava (Psidium guajava L.) seeds brought by germination to those in red bean (Vigna angularis) and winter wheat (Triticum aestivum L.) 498:672 The changes of selected carbohydrates in guava (Psidium guajava L.) seeds brought by germination to those in red bean (Vigna angularis) and winter wheat (Triticum aestivum L.) were compared. 28720961 9 11 theme carbohydrate 1233:1244 arg1 contents 1246:1253 the soluble carbohydrate contents 1221:1253 the soluble carbohydrate contents in red beans and guava seeds 1221:1282 The starch contents of all the seeds decreased, but the soluble carbohydrate contents in red beans and guava seeds increased significantly by the end of germination, suggesting the transient oversupply of reserve metabolites. 28720961 10 12 theme present 1526:1532 arg1 enzymes 1518:1524 cellulose-degrading enzymes 1498:1524 cellulose-degrading enzymes present 1498:1532 The content of hydrolyzed polysaccharides increased in the germinated seeds with detectable amounts of cellulose-degrading enzymes present, indicating improved value as feed. 28720961 2 13 theme dietary 271:277 arg1 content 285:291 their high dietary fiber content 260:291 their high dietary fiber content 260:291 Their high carbohydrate contents may suit the carbohydrate needs of the feed sector but their high dietary fiber content limits their feed value. 28720961 4 14 dep Triticum 652:659 arg1 L. 670:671 Triticum aestivum L. 652:671 Triticum aestivum L. 652:671 The changes of selected carbohydrates in guava (Psidium guajava L.) seeds brought by germination to those in red bean (Vigna angularis) and winter wheat (Triticum aestivum L.) were compared. 28720961 11 15 theme low-cost 1655:1662 arg1 supplements 1676:1686 low-cost animal feed supplements 1655:1686 low-cost animal feed supplements 1655:1686 Further research is warranted to explore the potential of guava seeds as a source of low-cost animal feed supplements. 28720961 3 16 theme fruit 337:341 arg1 seeds 343:347 fruit seeds 337:347 fruit seeds 337:347 The feed values of fruit seeds can be improved through germination, which involves the mobilization of nutrients through seed enzymes and alters the seed carbohydrate composition. 28720961 4 17 dep Psidium 546:552 arg1 L. 562:563 Psidium guajava L. 546:563 Psidium guajava L. 546:563 The changes of selected carbohydrates in guava (Psidium guajava L.) seeds brought by germination to those in red bean (Vigna angularis) and winter wheat (Triticum aestivum L.) were compared. 28720961 11 18 theme Further 1570:1576 arg1 research 1578:1585 Further research 1570:1585 Further research 1570:1585 Further research is warranted to explore the potential of guava seeds as a source of low-cost animal feed supplements. 28720961 2 19 theme high 266:269 arg1 content 285:291 their high dietary fiber content 260:291 their high dietary fiber content 260:291 Their high carbohydrate contents may suit the carbohydrate needs of the feed sector but their high dietary fiber content limits their feed value. 28720961 2 20 theme feed 306:309 arg1 value 311:315 their feed value 300:315 their feed value 300:315 Their high carbohydrate contents may suit the carbohydrate needs of the feed sector but their high dietary fiber content limits their feed value. 28720961 3 21 theme feed 322:325 arg1 values 327:332 The feed values 318:332 The feed values of fruit seeds 318:347 The feed values of fruit seeds can be improved through germination, which involves the mobilization of nutrients through seed enzymes and alters the seed carbohydrate composition. 28720961 7 22 theme cellulase 1038:1046 arg1 action 1028:1033 the action 1024:1033 the action of cellulase 1024:1046 Guava seeds were rich in cellulose (402.2 mg/g), which decreased progressively during germination, probably through the action of cellulase. 28720961 7 23 theme Guava 908:912 arg1 seeds 914:918 Guava seeds 908:918 Guava seeds 908:918 Guava seeds were rich in cellulose (402.2 mg/g), which decreased progressively during germination, probably through the action of cellulase. 28720961 1 24 theme processing 151:160 arg1 industry 162:169 the guava processing industry 141:169 the guava processing industry 141:169 Guava seeds are produced as a waste product by the guava processing industry. 28720961 9 25 theme red 1258:1260 arg1 beans 1262:1266 red beans 1258:1266 red beans 1258:1266 The starch contents of all the seeds decreased, but the soluble carbohydrate contents in red beans and guava seeds increased significantly by the end of germination, suggesting the transient oversupply of reserve metabolites. 28720961 8 26 theme cellulase 1158:1166 arg1 content 1091:1097 the highest starch content 1072:1097 the highest starch content (412.2 mg/g) 1072:1110 Winter wheat contained the highest starch content (412.2 mg/g) and also distinct quantities of α-amylase and cellulase. 28720961 8 26 theme cellulase 1158:1166 arg1 quantities 1130:1139 distinct quantities 1121:1139 distinct quantities of α-amylase and cellulase 1121:1166 Winter wheat contained the highest starch content (412.2 mg/g) and also distinct quantities of α-amylase and cellulase. 28720961 8 26 theme cellulase 1158:1166 arg1 412.2 mg/g 1100:1109 412.2 mg/g 1100:1109 412.2 mg/g 1100:1109 Winter wheat contained the highest starch content (412.2 mg/g) and also distinct quantities of α-amylase and cellulase. 28720961 8 27 theme distinct 1121:1128 arg1 quantities 1130:1139 distinct quantities 1121:1139 distinct quantities of α-amylase and cellulase 1121:1166 Winter wheat contained the highest starch content (412.2 mg/g) and also distinct quantities of α-amylase and cellulase. 28720961 9 28 theme metabolites 1382:1392 arg1 oversupply 1360:1369 the transient oversupply 1346:1369 the transient oversupply of reserve metabolites 1346:1392 The starch contents of all the seeds decreased, but the soluble carbohydrate contents in red beans and guava seeds increased significantly by the end of germination, suggesting the transient oversupply of reserve metabolites. 28720961 5 29 theme resistant 747:755 arg1 starch 757:762 resistant starch 747:762 resistant starch 747:762 The contents of soluble carbohydrates, digestible starch, resistant starch and cellulose in the seeds were determined. 28720961 5 30 theme carbohydrates 713:725 arg1 contents 693:700 The contents 689:700 The contents of soluble carbohydrates, digestible starch, resistant starch and cellulose in the seeds 689:789 The contents of soluble carbohydrates, digestible starch, resistant starch and cellulose in the seeds were determined. 28720961 8 31 theme starch 1084:1089 arg1 content 1091:1097 the highest starch content 1072:1097 the highest starch content (412.2 mg/g) 1072:1110 Winter wheat contained the highest starch content (412.2 mg/g) and also distinct quantities of α-amylase and cellulase. 28720961 8 31 theme starch 1084:1089 arg1 412.2 mg/g 1100:1109 412.2 mg/g 1100:1109 412.2 mg/g 1100:1109 Winter wheat contained the highest starch content (412.2 mg/g) and also distinct quantities of α-amylase and cellulase. 28720961 10 32 theme detectable 1476:1485 arg1 enzymes 1518:1524 cellulose-degrading enzymes 1498:1524 cellulose-degrading enzymes present 1498:1532 The content of hydrolyzed polysaccharides increased in the germinated seeds with detectable amounts of cellulose-degrading enzymes present, indicating improved value as feed. 28720961 10 32 theme detectable 1476:1485 arg1 amounts 1487:1493 detectable amounts 1476:1493 detectable amounts of cellulose-degrading enzymes present 1476:1532 The content of hydrolyzed polysaccharides increased in the germinated seeds with detectable amounts of cellulose-degrading enzymes present, indicating improved value as feed. 28720961 7 33 from cellulose 933:941 arg1 rich 925:928 rich 925:928 rich 925:928 Guava seeds were rich in cellulose (402.2 mg/g), which decreased progressively during germination, probably through the action of cellulase. 28720961 5 34 theme starch 757:762 arg1 contents 693:700 The contents 689:700 The contents of soluble carbohydrates, digestible starch, resistant starch and cellulose in the seeds 689:789 The contents of soluble carbohydrates, digestible starch, resistant starch and cellulose in the seeds were determined. 28720961 4 35 theme guava 539:543 arg1 seeds 566:570 guava (Psidium guajava L.) seeds 539:570 guava (Psidium guajava L.) seeds 539:570 The changes of selected carbohydrates in guava (Psidium guajava L.) seeds brought by germination to those in red bean (Vigna angularis) and winter wheat (Triticum aestivum L.) were compared. 28720961 11 36 theme supplements 1676:1686 arg1 potential 1615:1623 the potential 1611:1623 the potential of guava seeds 1611:1638 Further research is warranted to explore the potential of guava seeds as a source of low-cost animal feed supplements. 28720961 11 36 theme supplements 1676:1686 arg1 source 1645:1650 a source 1643:1650 a source of low-cost animal feed supplements 1643:1686 Further research is warranted to explore the potential of guava seeds as a source of low-cost animal feed supplements. 28720961 1 37 theme Guava 94:98 arg1 seeds 100:104 Guava seeds 94:104 Guava seeds 94:104 Guava seeds are produced as a waste product by the guava processing industry. 28720961 1 37 theme Guava 94:98 arg1 product 130:136 a waste product 122:136 a waste product 122:136 Guava seeds are produced as a waste product by the guava processing industry. 28720961 3 38 theme seeds 343:347 arg1 values 327:332 The feed values 318:332 The feed values of fruit seeds 318:347 The feed values of fruit seeds can be improved through germination, which involves the mobilization of nutrients through seed enzymes and alters the seed carbohydrate composition. 28720961 9 39 theme guava 1272:1276 arg1 seeds 1278:1282 guava seeds 1272:1282 guava seeds 1272:1282 The starch contents of all the seeds decreased, but the soluble carbohydrate contents in red beans and guava seeds increased significantly by the end of germination, suggesting the transient oversupply of reserve metabolites. 28720961 10 40 theme germinated 1454:1463 arg1 seeds 1465:1469 the germinated seeds 1450:1469 the germinated seeds 1450:1469 The content of hydrolyzed polysaccharides increased in the germinated seeds with detectable amounts of cellulose-degrading enzymes present, indicating improved value as feed. 28720961 9 41 theme reserve 1374:1380 arg1 metabolites 1382:1392 reserve metabolites 1374:1392 reserve metabolites 1374:1392 The starch contents of all the seeds decreased, but the soluble carbohydrate contents in red beans and guava seeds increased significantly by the end of germination, suggesting the transient oversupply of reserve metabolites. 28720961 11 42 theme seeds 1634:1638 arg1 potential 1615:1623 the potential 1611:1623 the potential of guava seeds 1611:1638 Further research is warranted to explore the potential of guava seeds as a source of low-cost animal feed supplements. 28720961 11 42 theme seeds 1634:1638 arg1 source 1645:1650 a source 1643:1650 a source of low-cost animal feed supplements 1643:1686 Further research is warranted to explore the potential of guava seeds as a source of low-cost animal feed supplements. 28720961 3 43 theme seed 439:442 arg1 enzymes 444:450 seed enzymes 439:450 seed enzymes 439:450 The feed values of fruit seeds can be improved through germination, which involves the mobilization of nutrients through seed enzymes and alters the seed carbohydrate composition. 28720961 5 44 theme cellulose 768:776 arg1 contents 693:700 The contents 689:700 The contents of soluble carbohydrates, digestible starch, resistant starch and cellulose in the seeds 689:789 The contents of soluble carbohydrates, digestible starch, resistant starch and cellulose in the seeds were determined. 28720961 6 45 theme radial 812:817 arg1 method 829:834 The radial diffusion method 808:834 The radial diffusion method 808:834 The radial diffusion method was used to detect carbohydrate-degrading enzymes in the seed extracts. 28720961 2 46 theme fiber 279:283 arg1 content 285:291 their high dietary fiber content 260:291 their high dietary fiber content 260:291 Their high carbohydrate contents may suit the carbohydrate needs of the feed sector but their high dietary fiber content limits their feed value. 28720961 11 47 theme feed 1671:1674 arg1 supplements 1676:1686 low-cost animal feed supplements 1655:1686 low-cost animal feed supplements 1655:1686 Further research is warranted to explore the potential of guava seeds as a source of low-cost animal feed supplements. 28720961 4 48 from carbohydrates 522:534 arg1 seeds 566:570 guava (Psidium guajava L.) seeds 539:570 guava (Psidium guajava L.) seeds 539:570 The changes of selected carbohydrates in guava (Psidium guajava L.) seeds brought by germination to those in red bean (Vigna angularis) and winter wheat (Triticum aestivum L.) were compared. 28720961 11 49 theme animal 1664:1669 arg1 supplements 1676:1686 low-cost animal feed supplements 1655:1686 low-cost animal feed supplements 1655:1686 Further research is warranted to explore the potential of guava seeds as a source of low-cost animal feed supplements. 28720961 4 50 theme red 607:609 arg1 bean 611:614 red bean 607:614 red bean (Vigna angularis) 607:632 The changes of selected carbohydrates in guava (Psidium guajava L.) seeds brought by germination to those in red bean (Vigna angularis) and winter wheat (Triticum aestivum L.) were compared. 28720961 4 50 theme red 607:609 arg1 angularis 623:631 Vigna angularis 617:631 Vigna angularis 617:631 The changes of selected carbohydrates in guava (Psidium guajava L.) seeds brought by germination to those in red bean (Vigna angularis) and winter wheat (Triticum aestivum L.) were compared. 28720961 3 51 theme nutrients 421:429 arg1 mobilization 405:416 the mobilization 401:416 the mobilization of nutrients through seed enzymes 401:450 The feed values of fruit seeds can be improved through germination, which involves the mobilization of nutrients through seed enzymes and alters the seed carbohydrate composition. 28720961 4 52 theme Vigna 617:621 arg1 bean 611:614 red bean 607:614 red bean (Vigna angularis) 607:632 The changes of selected carbohydrates in guava (Psidium guajava L.) seeds brought by germination to those in red bean (Vigna angularis) and winter wheat (Triticum aestivum L.) were compared. 28720961 4 52 theme Vigna 617:621 arg1 angularis 623:631 Vigna angularis 617:631 Vigna angularis 617:631 The changes of selected carbohydrates in guava (Psidium guajava L.) seeds brought by germination to those in red bean (Vigna angularis) and winter wheat (Triticum aestivum L.) were compared. 28720961 5 53 theme digestible 728:737 arg1 starch 739:744 digestible starch 728:744 digestible starch 728:744 The contents of soluble carbohydrates, digestible starch, resistant starch and cellulose in the seeds were determined. 28720961 8 54 theme α-amylase 1144:1152 arg1 content 1091:1097 the highest starch content 1072:1097 the highest starch content (412.2 mg/g) 1072:1110 Winter wheat contained the highest starch content (412.2 mg/g) and also distinct quantities of α-amylase and cellulase. 28720961 8 54 theme α-amylase 1144:1152 arg1 quantities 1130:1139 distinct quantities 1121:1139 distinct quantities of α-amylase and cellulase 1121:1166 Winter wheat contained the highest starch content (412.2 mg/g) and also distinct quantities of α-amylase and cellulase. 28720961 8 54 theme α-amylase 1144:1152 arg1 412.2 mg/g 1100:1109 412.2 mg/g 1100:1109 412.2 mg/g 1100:1109 Winter wheat contained the highest starch content (412.2 mg/g) and also distinct quantities of α-amylase and cellulase. 28720961 2 55 dep carbohydrate 218:229 arg1 needs 231:235 needs 231:235 needs 231:235 Their high carbohydrate contents may suit the carbohydrate needs of the feed sector but their high dietary fiber content limits their feed value. 28720961 5 56 theme starch 739:744 arg1 contents 693:700 The contents 689:700 The contents of soluble carbohydrates, digestible starch, resistant starch and cellulose in the seeds 689:789 The contents of soluble carbohydrates, digestible starch, resistant starch and cellulose in the seeds were determined. 28720961 6 57 theme seed 893:896 arg1 extracts 898:905 the seed extracts 889:905 the seed extracts 889:905 The radial diffusion method was used to detect carbohydrate-degrading enzymes in the seed extracts. 28720961 10 58 theme enzymes 1518:1524 arg1 enzymes 1518:1524 cellulose-degrading enzymes 1498:1524 cellulose-degrading enzymes present 1498:1532 The content of hydrolyzed polysaccharides increased in the germinated seeds with detectable amounts of cellulose-degrading enzymes present, indicating improved value as feed. 28720961 10 58 theme enzymes 1518:1524 arg1 amounts 1487:1493 detectable amounts 1476:1493 detectable amounts of cellulose-degrading enzymes present 1476:1532 The content of hydrolyzed polysaccharides increased in the germinated seeds with detectable amounts of cellulose-degrading enzymes present, indicating improved value as feed. 28720961 11 59 theme guava 1628:1632 arg1 seeds 1634:1638 guava seeds 1628:1638 guava seeds 1628:1638 Further research is warranted to explore the potential of guava seeds as a source of low-cost animal feed supplements. 28720961 8 60 contain contained 1062:1070 arg1 wheat 1056:1060 Winter wheat 1049:1060 Winter wheat 1049:1060 Winter wheat contained the highest starch content (412.2 mg/g) and also distinct quantities of α-amylase and cellulase. 28720961 8 60 contain contained 1062:1070 arg2 412.2 mg/g 1100:1109 412.2 mg/g 1100:1109 412.2 mg/g 1100:1109 Winter wheat contained the highest starch content (412.2 mg/g) and also distinct quantities of α-amylase and cellulase. 28720961 8 60 contain contained 1062:1070 arg2 quantities 1130:1139 distinct quantities 1121:1139 distinct quantities of α-amylase and cellulase 1121:1166 Winter wheat contained the highest starch content (412.2 mg/g) and also distinct quantities of α-amylase and cellulase. 28720961 8 60 contain contained 1062:1070 arg2 content 1091:1097 the highest starch content 1072:1097 the highest starch content (412.2 mg/g) 1072:1110 Winter wheat contained the highest starch content (412.2 mg/g) and also distinct quantities of α-amylase and cellulase. 28720961 4 61 from changes 502:508 arg1 seeds 566:570 guava (Psidium guajava L.) seeds 539:570 guava (Psidium guajava L.) seeds 539:570 The changes of selected carbohydrates in guava (Psidium guajava L.) seeds brought by germination to those in red bean (Vigna angularis) and winter wheat (Triticum aestivum L.) were compared. 28720961 4 62 theme carbohydrates 522:534 arg1 changes 502:508 The changes 498:508 The changes of selected carbohydrates in guava (Psidium guajava L.) seeds brought by germination to those in red bean (Vigna angularis) and winter wheat (Triticum aestivum L.) 498:672 The changes of selected carbohydrates in guava (Psidium guajava L.) seeds brought by germination to those in red bean (Vigna angularis) and winter wheat (Triticum aestivum L.) were compared. 28720961 8 63 theme Winter 1049:1054 arg1 wheat 1056:1060 Winter wheat 1049:1060 Winter wheat 1049:1060 Winter wheat contained the highest starch content (412.2 mg/g) and also distinct quantities of α-amylase and cellulase. 28720961 10 64 theme cellulose-degrading 1498:1516 arg1 enzymes 1518:1524 cellulose-degrading enzymes 1498:1524 cellulose-degrading enzymes present 1498:1532 The content of hydrolyzed polysaccharides increased in the germinated seeds with detectable amounts of cellulose-degrading enzymes present, indicating improved value as feed. 28720961 10 65 theme hydrolyzed 1410:1419 arg1 polysaccharides 1421:1435 hydrolyzed polysaccharides 1410:1435 hydrolyzed polysaccharides 1410:1435 The content of hydrolyzed polysaccharides increased in the germinated seeds with detectable amounts of cellulose-degrading enzymes present, indicating improved value as feed. 28720961 7 66 from rich 925:928 arg1 cellulose 933:941 cellulose 933:941 cellulose (402.2 mg/g) 933:954 Guava seeds were rich in cellulose (402.2 mg/g), which decreased progressively during germination, probably through the action of cellulase. 28720961 7 66 from rich 925:928 arg1 402.2 mg/g 944:953 402.2 mg/g 944:953 402.2 mg/g 944:953 Guava seeds were rich in cellulose (402.2 mg/g), which decreased progressively during germination, probably through the action of cellulase. 28720961 3 67 theme seed 467:470 arg1 composition 485:495 the seed carbohydrate composition 463:495 the seed carbohydrate composition 463:495 The feed values of fruit seeds can be improved through germination, which involves the mobilization of nutrients through seed enzymes and alters the seed carbohydrate composition. 28720961 4 68 theme selected 513:520 arg1 carbohydrates 522:534 selected carbohydrates 513:534 selected carbohydrates in guava (Psidium guajava L.) seeds 513:570 The changes of selected carbohydrates in guava (Psidium guajava L.) seeds brought by germination to those in red bean (Vigna angularis) and winter wheat (Triticum aestivum L.) were compared. 28720961 9 69 theme seeds 1200:1204 arg1 contents 1180:1187 The starch contents 1169:1187 The starch contents of all the seeds 1169:1204 The starch contents of all the seeds decreased, but the soluble carbohydrate contents in red beans and guava seeds increased significantly by the end of germination, suggesting the transient oversupply of reserve metabolites. 28720961 2 70 theme sector 249:254 arg1 carbohydrate 218:229 carbohydrate 218:229 carbohydrate 218:229 Their high carbohydrate contents may suit the carbohydrate needs of the feed sector but their high dietary fiber content limits their feed value. 28720961 9 71 from contents 1246:1253 arg1 seeds 1278:1282 guava seeds 1272:1282 guava seeds 1272:1282 The starch contents of all the seeds decreased, but the soluble carbohydrate contents in red beans and guava seeds increased significantly by the end of germination, suggesting the transient oversupply of reserve metabolites. 28720961 9 71 from contents 1246:1253 arg1 beans 1262:1266 red beans 1258:1266 red beans 1258:1266 The starch contents of all the seeds decreased, but the soluble carbohydrate contents in red beans and guava seeds increased significantly by the end of germination, suggesting the transient oversupply of reserve metabolites. 28720961 2 72 theme carbohydrate 183:194 arg1 contents 196:203 Their high carbohydrate contents 172:203 Their high carbohydrate contents 172:203 Their high carbohydrate contents may suit the carbohydrate needs of the feed sector but their high dietary fiber content limits their feed value. 28720961 2 73 theme feed 244:247 arg1 sector 249:254 the feed sector 240:254 the feed sector 240:254 Their high carbohydrate contents may suit the carbohydrate needs of the feed sector but their high dietary fiber content limits their feed value. 28720961 10 74 theme polysaccharides 1421:1435 arg1 content 1399:1405 The content 1395:1405 The content of hydrolyzed polysaccharides 1395:1435 The content of hydrolyzed polysaccharides increased in the germinated seeds with detectable amounts of cellulose-degrading enzymes present, indicating improved value as feed. 28720961 1 75 theme waste 124:128 arg1 seeds 100:104 Guava seeds 94:104 Guava seeds 94:104 Guava seeds are produced as a waste product by the guava processing industry. 28720961 1 75 theme waste 124:128 arg1 product 130:136 a waste product 122:136 a waste product 122:136 Guava seeds are produced as a waste product by the guava processing industry. 28720961 9 76 theme germination 1322:1332 arg1 end 1315:1317 the end 1311:1317 the end of germination 1311:1332 The starch contents of all the seeds decreased, but the soluble carbohydrate contents in red beans and guava seeds increased significantly by the end of germination, suggesting the transient oversupply of reserve metabolites. 28720961 0 77 theme germination-induced 52:70 arg1 changes 85:91 germination-induced carbohydrate changes 52:91 germination-induced carbohydrate changes 52:91 Valorizing guava (Psidium guajava L.) seeds through germination-induced carbohydrate changes. 28720961 2 78 theme high 178:181 arg1 contents 196:203 Their high carbohydrate contents 172:203 Their high carbohydrate contents 172:203 Their high carbohydrate contents may suit the carbohydrate needs of the feed sector but their high dietary fiber content limits their feed value. 28720961 9 79 theme starch 1173:1178 arg1 contents 1180:1187 The starch contents 1169:1187 The starch contents of all the seeds 1169:1204 The starch contents of all the seeds decreased, but the soluble carbohydrate contents in red beans and guava seeds increased significantly by the end of germination, suggesting the transient oversupply of reserve metabolites. 28720961 4 80 theme winter 638:643 arg1 wheat 645:649 winter wheat 638:649 winter wheat (Triticum aestivum L.) 638:672 The changes of selected carbohydrates in guava (Psidium guajava L.) seeds brought by germination to those in red bean (Vigna angularis) and winter wheat (Triticum aestivum L.) were compared. 28720961 4 80 theme winter 638:643 arg1 Triticum 652:659 Triticum 652:659 Triticum 652:659 The changes of selected carbohydrates in guava (Psidium guajava L.) seeds brought by germination to those in red bean (Vigna angularis) and winter wheat (Triticum aestivum L.) were compared. 28720961 8 81 theme highest 1076:1082 arg1 content 1091:1097 the highest starch content 1072:1097 the highest starch content (412.2 mg/g) 1072:1110 Winter wheat contained the highest starch content (412.2 mg/g) and also distinct quantities of α-amylase and cellulase. 28720961 8 81 theme highest 1076:1082 arg1 412.2 mg/g 1100:1109 412.2 mg/g 1100:1109 412.2 mg/g 1100:1109 Winter wheat contained the highest starch content (412.2 mg/g) and also distinct quantities of α-amylase and cellulase. 28720961 10 82 theme improved 1546:1553 arg1 value 1555:1559 improved value 1546:1559 improved value 1546:1559 The content of hydrolyzed polysaccharides increased in the germinated seeds with detectable amounts of cellulose-degrading enzymes present, indicating improved value as feed. 24186210 6 0 theme OGT 794:796 arg1 mouse 814:818 a constitutive cardiomyocyte-specific (cm)OGT KO (c-cmOGT KO) mouse 752:818 a constitutive cardiomyocyte-specific (cm)OGT KO (c-cmOGT KO) mouse 752:818 Initially, we characterized a constitutive cardiomyocyte-specific (cm)OGT KO (c-cmOGT KO) mouse and found that only 12% of the c-cmOGT KO mice survived to weaning age (4 wk old); the surviving animals were smaller than their wild-type littermates, had dilated hearts, and showed overt signs of heart failure. 24186210 9 1 theme stress 1325:1330 arg1 involvement 1288:1298 the potential involvement 1274:1298 the potential involvement of endoplasmic reticulum stress 1274:1330 Histopathology of the KO hearts indicated the potential involvement of endoplasmic reticulum stress, directing us to evaluate expression of 78-kDa glucose-regulated protein and protein disulfide isomerase, which were elevated. 24186210 4 2 theme body 577:580 arg1 animals 596:602 total body knockout (KO) animals 571:602 total body knockout (KO) animals 571:602 Yet, little is known about how OGT affects cardiac function because total body knockout (KO) animals are not viable. 24186210 6 3 theme cm 791:792 arg1 mouse 814:818 a constitutive cardiomyocyte-specific (cm)OGT KO (c-cmOGT KO) mouse 752:818 a constitutive cardiomyocyte-specific (cm)OGT KO (c-cmOGT KO) mouse 752:818 Initially, we characterized a constitutive cardiomyocyte-specific (cm)OGT KO (c-cmOGT KO) mouse and found that only 12% of the c-cmOGT KO mice survived to weaning age (4 wk old); the surviving animals were smaller than their wild-type littermates, had dilated hearts, and showed overt signs of heart failure. 24186210 5 4 from involvement 668:678 arg1 maturation 712:721 cardiac maturation 704:721 cardiac maturation 704:721 Presently, we sought to establish the potential involvement of cardiomyocyte Ogt in cardiac maturation. 24186210 3 5 theme acute 412:416 arg1 increases 418:426 acute increases 412:426 acute increases in protein O-GlcNAcylation 412:453 Several groups, including our own, have shown that acute increases in protein O-GlcNAcylation are cardioprotective both in vitro and in vivo. 24186210 10 6 theme mice 1480:1483 arg1 groups 1470:1475 Additional groups 1459:1475 Additional groups of mice 1459:1483 Additional groups of mice were subjected to inducible deletion of cmOGT, which did not produce overt dysfunction within the first couple of weeks of deletion. 24186210 10 6 theme mice 1480:1483 arg1 mice 1480:1483 mice 1480:1483 mice 1480:1483 Additional groups of mice were subjected to inducible deletion of cmOGT, which did not produce overt dysfunction within the first couple of weeks of deletion. 24186210 6 7 theme cardiomyocyte-specific 767:788 arg1 mouse 814:818 a constitutive cardiomyocyte-specific (cm)OGT KO (c-cmOGT KO) mouse 752:818 a constitutive cardiomyocyte-specific (cm)OGT KO (c-cmOGT KO) mouse 752:818 Initially, we characterized a constitutive cardiomyocyte-specific (cm)OGT KO (c-cmOGT KO) mouse and found that only 12% of the c-cmOGT KO mice survived to weaning age (4 wk old); the surviving animals were smaller than their wild-type littermates, had dilated hearts, and showed overt signs of heart failure. 24186210 12 8 theme ventricular 1869:1879 arg1 dysfunction 1881:1891 progressive ventricular dysfunction 1857:1891 progressive ventricular dysfunction 1857:1891 Thus, cardiomyocyte Ogt is necessary for maturation of the mammalian heart, and inducible deletion of cmOGT in the adult mouse produces progressive ventricular dysfunction. 24186210 11 9 theme progressive 1693:1703 arg1 cardiomyopathy 1705:1718 gradual and progressive cardiomyopathy 1681:1718 gradual and progressive cardiomyopathy 1681:1718 Yet, long-term loss (via inducible deletion) of cmOGT produced gradual and progressive cardiomyopathy. 24186210 10 10 theme inducible 1503:1511 arg1 deletion 1513:1520 inducible deletion 1503:1520 inducible deletion 1503:1520 Additional groups of mice were subjected to inducible deletion of cmOGT, which did not produce overt dysfunction within the first couple of weeks of deletion. 24186210 11 11 theme gradual 1681:1687 arg1 cardiomyopathy 1705:1718 gradual and progressive cardiomyopathy 1681:1718 gradual and progressive cardiomyopathy 1681:1718 Yet, long-term loss (via inducible deletion) of cmOGT produced gradual and progressive cardiomyopathy. 24186210 2 12 theme posttranslational 282:298 arg1 modification 300:311 the posttranslational modification 278:311 the posttranslational modification known as O-GlcNAc to various cellular proteins 278:358 In mature cells, this enzyme catalyzes the posttranslational modification known as O-GlcNAc to various cellular proteins. 24186210 9 13 theme 78-kDa 1372:1377 arg1 protein 1397:1403 78-kDa glucose-regulated protein 1372:1403 78-kDa glucose-regulated protein 1372:1403 Histopathology of the KO hearts indicated the potential involvement of endoplasmic reticulum stress, directing us to evaluate expression of 78-kDa glucose-regulated protein and protein disulfide isomerase, which were elevated. 24186210 12 14 theme adult 1836:1840 arg1 mouse 1842:1846 the adult mouse 1832:1846 the adult mouse 1832:1846 Thus, cardiomyocyte Ogt is necessary for maturation of the mammalian heart, and inducible deletion of cmOGT in the adult mouse produces progressive ventricular dysfunction. 24186210 5 15 theme cardiomyocyte 683:695 arg1 Ogt 697:699 cardiomyocyte Ogt 683:699 cardiomyocyte Ogt 683:699 Presently, we sought to establish the potential involvement of cardiomyocyte Ogt in cardiac maturation. 24186210 1 16 theme cell 202:205 arg1 viability 207:215 embryonic stem cell viability 187:215 embryonic stem cell viability 187:215 The singly coded gene O-linked-β-N-acetylglucosamine (O-GlcNAc) transferase (Ogt) resides on the X chromosome and is necessary for embryonic stem cell viability during embryogenesis. 24186210 8 17 theme glycolytic 1122:1131 arg1 genes 1133:1137 Several glycolytic genes 1114:1137 Several glycolytic genes 1114:1137 Several glycolytic genes were also upregulated; however, there were no gross changes in mitochondrial O2 consumption. 24186210 9 18 theme protein 1409:1415 arg1 isomerase 1427:1435 protein disulfide isomerase 1409:1435 protein disulfide isomerase 1409:1435 Histopathology of the KO hearts indicated the potential involvement of endoplasmic reticulum stress, directing us to evaluate expression of 78-kDa glucose-regulated protein and protein disulfide isomerase, which were elevated. 24186210 6 19 theme mice 862:865 arg1 mice 862:865 the c-cmOGT KO mice 847:865 the c-cmOGT KO mice 847:865 Initially, we characterized a constitutive cardiomyocyte-specific (cm)OGT KO (c-cmOGT KO) mouse and found that only 12% of the c-cmOGT KO mice survived to weaning age (4 wk old); the surviving animals were smaller than their wild-type littermates, had dilated hearts, and showed overt signs of heart failure. 24186210 6 19 theme mice 862:865 arg1 % 842:842 only 12% 835:842 only 12% of the c-cmOGT KO mice 835:865 Initially, we characterized a constitutive cardiomyocyte-specific (cm)OGT KO (c-cmOGT KO) mouse and found that only 12% of the c-cmOGT KO mice survived to weaning age (4 wk old); the surviving animals were smaller than their wild-type littermates, had dilated hearts, and showed overt signs of heart failure. 24186210 6 20 dep age 887:889 arg1 old 897:899 old 897:899 old 897:899 Initially, we characterized a constitutive cardiomyocyte-specific (cm)OGT KO (c-cmOGT KO) mouse and found that only 12% of the c-cmOGT KO mice survived to weaning age (4 wk old); the surviving animals were smaller than their wild-type littermates, had dilated hearts, and showed overt signs of heart failure. 24186210 11 21 theme inducible 1643:1651 arg1 deletion 1653:1660 inducible deletion 1643:1660 inducible deletion 1643:1660 Yet, long-term loss (via inducible deletion) of cmOGT produced gradual and progressive cardiomyopathy. 24186210 9 22 theme isomerase 1427:1435 arg1 expression 1358:1367 expression 1358:1367 expression of 78-kDa glucose-regulated protein and protein disulfide isomerase, which were elevated 1358:1456 Histopathology of the KO hearts indicated the potential involvement of endoplasmic reticulum stress, directing us to evaluate expression of 78-kDa glucose-regulated protein and protein disulfide isomerase, which were elevated. 24186210 9 23 theme disulfide 1417:1425 arg1 isomerase 1427:1435 protein disulfide isomerase 1409:1435 protein disulfide isomerase 1409:1435 Histopathology of the KO hearts indicated the potential involvement of endoplasmic reticulum stress, directing us to evaluate expression of 78-kDa glucose-regulated protein and protein disulfide isomerase, which were elevated. 24186210 8 24 theme mitochondrial 1202:1214 arg1 consumption 1219:1229 mitochondrial O2 consumption 1202:1229 mitochondrial O2 consumption 1202:1229 Several glycolytic genes were also upregulated; however, there were no gross changes in mitochondrial O2 consumption. 24186210 6 25 theme surviving 907:915 arg1 animals 917:923 the surviving animals 903:923 the surviving animals 903:923 Initially, we characterized a constitutive cardiomyocyte-specific (cm)OGT KO (c-cmOGT KO) mouse and found that only 12% of the c-cmOGT KO mice survived to weaning age (4 wk old); the surviving animals were smaller than their wild-type littermates, had dilated hearts, and showed overt signs of heart failure. 24186210 6 25 theme surviving 907:915 arg1 smaller 930:936 smaller 930:936 smaller 930:936 Initially, we characterized a constitutive cardiomyocyte-specific (cm)OGT KO (c-cmOGT KO) mouse and found that only 12% of the c-cmOGT KO mice survived to weaning age (4 wk old); the surviving animals were smaller than their wild-type littermates, had dilated hearts, and showed overt signs of heart failure. 24186210 6 26 contain had 972:974 arg2 hearts 984:989 dilated hearts 976:989 dilated hearts 976:989 Initially, we characterized a constitutive cardiomyocyte-specific (cm)OGT KO (c-cmOGT KO) mouse and found that only 12% of the c-cmOGT KO mice survived to weaning age (4 wk old); the surviving animals were smaller than their wild-type littermates, had dilated hearts, and showed overt signs of heart failure. 24186210 6 26 contain had 972:974 arg1 animals 917:923 the surviving animals 903:923 the surviving animals 903:923 Initially, we characterized a constitutive cardiomyocyte-specific (cm)OGT KO (c-cmOGT KO) mouse and found that only 12% of the c-cmOGT KO mice survived to weaning age (4 wk old); the surviving animals were smaller than their wild-type littermates, had dilated hearts, and showed overt signs of heart failure. 24186210 6 26 contain had 972:974 arg1 smaller 930:936 smaller 930:936 smaller 930:936 Initially, we characterized a constitutive cardiomyocyte-specific (cm)OGT KO (c-cmOGT KO) mouse and found that only 12% of the c-cmOGT KO mice survived to weaning age (4 wk old); the surviving animals were smaller than their wild-type littermates, had dilated hearts, and showed overt signs of heart failure. 24186210 11 27 theme cmOGT 1666:1670 arg1 loss 1633:1636 long-term loss 1623:1636 long-term loss (via inducible deletion) of cmOGT 1623:1670 Yet, long-term loss (via inducible deletion) of cmOGT produced gradual and progressive cardiomyopathy. 24186210 1 28 theme X 153:153 arg1 chromosome 155:164 the X chromosome 149:164 the X chromosome 149:164 The singly coded gene O-linked-β-N-acetylglucosamine (O-GlcNAc) transferase (Ogt) resides on the X chromosome and is necessary for embryonic stem cell viability during embryogenesis. 24186210 3 29 theme Several 361:367 arg1 own 391:393 own 391:393 own 391:393 Several groups, including our own, have shown that acute increases in protein O-GlcNAcylation are cardioprotective both in vitro and in vivo. 24186210 3 29 theme Several 361:367 arg1 groups 369:374 Several groups 361:374 Several groups 361:374 Several groups, including our own, have shown that acute increases in protein O-GlcNAcylation are cardioprotective both in vitro and in vivo. 24186210 12 30 theme cmOGT 1823:1827 arg1 deletion 1811:1818 inducible deletion 1801:1818 inducible deletion of cmOGT in the adult mouse 1801:1846 Thus, cardiomyocyte Ogt is necessary for maturation of the mammalian heart, and inducible deletion of cmOGT in the adult mouse produces progressive ventricular dysfunction. 24186210 12 31 theme heart 1790:1794 arg1 maturation 1762:1771 maturation 1762:1771 maturation of the mammalian heart 1762:1794 Thus, cardiomyocyte Ogt is necessary for maturation of the mammalian heart, and inducible deletion of cmOGT in the adult mouse produces progressive ventricular dysfunction. 24186210 1 32 theme gene 73:76 arg1 Ogt 133:135 Ogt 133:135 Ogt 133:135 The singly coded gene O-linked-β-N-acetylglucosamine (O-GlcNAc) transferase (Ogt) resides on the X chromosome and is necessary for embryonic stem cell viability during embryogenesis. 24186210 1 32 theme gene 73:76 arg1 transferase 120:130 The singly coded gene O-linked-β-N-acetylglucosamine (O-GlcNAc) transferase 56:130 The singly coded gene O-linked-β-N-acetylglucosamine (O-GlcNAc) transferase (Ogt) 56:136 The singly coded gene O-linked-β-N-acetylglucosamine (O-GlcNAc) transferase (Ogt) resides on the X chromosome and is necessary for embryonic stem cell viability during embryogenesis. 24186210 1 32 theme gene 73:76 arg1 necessary 173:181 necessary 173:181 necessary 173:181 The singly coded gene O-linked-β-N-acetylglucosamine (O-GlcNAc) transferase (Ogt) resides on the X chromosome and is necessary for embryonic stem cell viability during embryogenesis. 24186210 6 33 theme dilated 976:982 arg1 hearts 984:989 dilated hearts 976:989 dilated hearts 976:989 Initially, we characterized a constitutive cardiomyocyte-specific (cm)OGT KO (c-cmOGT KO) mouse and found that only 12% of the c-cmOGT KO mice survived to weaning age (4 wk old); the surviving animals were smaller than their wild-type littermates, had dilated hearts, and showed overt signs of heart failure. 24186210 10 34 theme overt 1554:1558 arg1 dysfunction 1560:1570 overt dysfunction 1554:1570 overt dysfunction 1554:1570 Additional groups of mice were subjected to inducible deletion of cmOGT, which did not produce overt dysfunction within the first couple of weeks of deletion. 24186210 0 35 theme Cardiomyocyte 0:12 arg1 Ogt 14:16 Cardiomyocyte Ogt 0:16 Cardiomyocyte Ogt 0:16 Cardiomyocyte Ogt is essential for postnatal viability. 24186210 6 36 theme wild-type 949:957 arg1 littermates 959:969 their wild-type littermates 943:969 their wild-type littermates 943:969 Initially, we characterized a constitutive cardiomyocyte-specific (cm)OGT KO (c-cmOGT KO) mouse and found that only 12% of the c-cmOGT KO mice survived to weaning age (4 wk old); the surviving animals were smaller than their wild-type littermates, had dilated hearts, and showed overt signs of heart failure. 24186210 10 37 dep first 1583:1587 arg1 couple 1589:1594 couple 1589:1594 couple 1589:1594 Additional groups of mice were subjected to inducible deletion of cmOGT, which did not produce overt dysfunction within the first couple of weeks of deletion. 24186210 7 38 theme KO 1055:1056 arg1 hearts 1058:1063 Dysfunctional c-cmOGT KO hearts 1033:1063 Dysfunctional c-cmOGT KO hearts 1033:1063 Dysfunctional c-cmOGT KO hearts were more fibrotic, apoptotic, and hypertrophic. 24186210 9 39 theme KO 1254:1255 arg1 hearts 1257:1262 the KO hearts 1250:1262 the KO hearts 1250:1262 Histopathology of the KO hearts indicated the potential involvement of endoplasmic reticulum stress, directing us to evaluate expression of 78-kDa glucose-regulated protein and protein disulfide isomerase, which were elevated. 24186210 2 40 theme cellular 342:349 arg1 proteins 351:358 various cellular proteins 334:358 various cellular proteins 334:358 In mature cells, this enzyme catalyzes the posttranslational modification known as O-GlcNAc to various cellular proteins. 24186210 7 41 theme Dysfunctional 1033:1045 arg1 hearts 1058:1063 Dysfunctional c-cmOGT KO hearts 1033:1063 Dysfunctional c-cmOGT KO hearts 1033:1063 Dysfunctional c-cmOGT KO hearts were more fibrotic, apoptotic, and hypertrophic. 24186210 6 42 theme KO 810:811 arg1 mouse 814:818 a constitutive cardiomyocyte-specific (cm)OGT KO (c-cmOGT KO) mouse 752:818 a constitutive cardiomyocyte-specific (cm)OGT KO (c-cmOGT KO) mouse 752:818 Initially, we characterized a constitutive cardiomyocyte-specific (cm)OGT KO (c-cmOGT KO) mouse and found that only 12% of the c-cmOGT KO mice survived to weaning age (4 wk old); the surviving animals were smaller than their wild-type littermates, had dilated hearts, and showed overt signs of heart failure. 24186210 12 43 theme cardiomyocyte 1727:1739 arg1 Ogt 1741:1743 cardiomyocyte Ogt 1727:1743 cardiomyocyte Ogt 1727:1743 Thus, cardiomyocyte Ogt is necessary for maturation of the mammalian heart, and inducible deletion of cmOGT in the adult mouse produces progressive ventricular dysfunction. 24186210 6 44 theme heart 1018:1022 arg1 failure 1024:1030 heart failure 1018:1030 heart failure 1018:1030 Initially, we characterized a constitutive cardiomyocyte-specific (cm)OGT KO (c-cmOGT KO) mouse and found that only 12% of the c-cmOGT KO mice survived to weaning age (4 wk old); the surviving animals were smaller than their wild-type littermates, had dilated hearts, and showed overt signs of heart failure. 24186210 9 45 theme potential 1278:1286 arg1 involvement 1288:1298 the potential involvement 1274:1298 the potential involvement of endoplasmic reticulum stress 1274:1330 Histopathology of the KO hearts indicated the potential involvement of endoplasmic reticulum stress, directing us to evaluate expression of 78-kDa glucose-regulated protein and protein disulfide isomerase, which were elevated. 24186210 4 46 theme knockout 582:589 arg1 animals 596:602 total body knockout (KO) animals 571:602 total body knockout (KO) animals 571:602 Yet, little is known about how OGT affects cardiac function because total body knockout (KO) animals are not viable. 24186210 3 47 from increases 418:426 arg1 O-GlcNAcylation 439:453 protein O-GlcNAcylation 431:453 protein O-GlcNAcylation 431:453 Several groups, including our own, have shown that acute increases in protein O-GlcNAcylation are cardioprotective both in vitro and in vivo. 24186210 6 48 theme KO 859:860 arg1 mice 862:865 the c-cmOGT KO mice 847:865 the c-cmOGT KO mice 847:865 Initially, we characterized a constitutive cardiomyocyte-specific (cm)OGT KO (c-cmOGT KO) mouse and found that only 12% of the c-cmOGT KO mice survived to weaning age (4 wk old); the surviving animals were smaller than their wild-type littermates, had dilated hearts, and showed overt signs of heart failure. 24186210 12 49 from deletion 1811:1818 arg1 mouse 1842:1846 the adult mouse 1832:1846 the adult mouse 1832:1846 Thus, cardiomyocyte Ogt is necessary for maturation of the mammalian heart, and inducible deletion of cmOGT in the adult mouse produces progressive ventricular dysfunction. 24186210 4 50 theme KO 592:593 arg1 animals 596:602 total body knockout (KO) animals 571:602 total body knockout (KO) animals 571:602 Yet, little is known about how OGT affects cardiac function because total body knockout (KO) animals are not viable. 24186210 10 51 theme Additional 1459:1468 arg1 groups 1470:1475 Additional groups 1459:1475 Additional groups of mice 1459:1483 Additional groups of mice were subjected to inducible deletion of cmOGT, which did not produce overt dysfunction within the first couple of weeks of deletion. 24186210 10 51 theme Additional 1459:1468 arg1 mice 1480:1483 mice 1480:1483 mice 1480:1483 Additional groups of mice were subjected to inducible deletion of cmOGT, which did not produce overt dysfunction within the first couple of weeks of deletion. 24186210 9 52 theme reticulum 1315:1323 arg1 stress 1325:1330 endoplasmic reticulum stress 1303:1330 endoplasmic reticulum stress 1303:1330 Histopathology of the KO hearts indicated the potential involvement of endoplasmic reticulum stress, directing us to evaluate expression of 78-kDa glucose-regulated protein and protein disulfide isomerase, which were elevated. 24186210 4 53 theme total 571:575 arg1 animals 596:602 total body knockout (KO) animals 571:602 total body knockout (KO) animals 571:602 Yet, little is known about how OGT affects cardiac function because total body knockout (KO) animals are not viable. 24186210 10 54 theme cmOGT 1525:1529 arg1 deletion 1513:1520 inducible deletion 1503:1520 inducible deletion 1503:1520 Additional groups of mice were subjected to inducible deletion of cmOGT, which did not produce overt dysfunction within the first couple of weeks of deletion. 24186210 6 55 theme constitutive 754:765 arg1 mouse 814:818 a constitutive cardiomyocyte-specific (cm)OGT KO (c-cmOGT KO) mouse 752:818 a constitutive cardiomyocyte-specific (cm)OGT KO (c-cmOGT KO) mouse 752:818 Initially, we characterized a constitutive cardiomyocyte-specific (cm)OGT KO (c-cmOGT KO) mouse and found that only 12% of the c-cmOGT KO mice survived to weaning age (4 wk old); the surviving animals were smaller than their wild-type littermates, had dilated hearts, and showed overt signs of heart failure. 24186210 12 56 theme progressive 1857:1867 arg1 dysfunction 1881:1891 progressive ventricular dysfunction 1857:1891 progressive ventricular dysfunction 1857:1891 Thus, cardiomyocyte Ogt is necessary for maturation of the mammalian heart, and inducible deletion of cmOGT in the adult mouse produces progressive ventricular dysfunction. 24186210 5 57 theme potential 658:666 arg1 involvement 668:678 the potential involvement 654:678 the potential involvement of cardiomyocyte Ogt in cardiac maturation 654:721 Presently, we sought to establish the potential involvement of cardiomyocyte Ogt in cardiac maturation. 24186210 2 58 theme various 334:340 arg1 proteins 351:358 various cellular proteins 334:358 various cellular proteins 334:358 In mature cells, this enzyme catalyzes the posttranslational modification known as O-GlcNAc to various cellular proteins. 24186210 9 59 theme glucose-regulated 1379:1395 arg1 protein 1397:1403 78-kDa glucose-regulated protein 1372:1403 78-kDa glucose-regulated protein 1372:1403 Histopathology of the KO hearts indicated the potential involvement of endoplasmic reticulum stress, directing us to evaluate expression of 78-kDa glucose-regulated protein and protein disulfide isomerase, which were elevated. 24186210 6 60 theme weaning 879:885 arg1 age 887:889 weaning age 879:889 weaning age (4 wk old) 879:900 Initially, we characterized a constitutive cardiomyocyte-specific (cm)OGT KO (c-cmOGT KO) mouse and found that only 12% of the c-cmOGT KO mice survived to weaning age (4 wk old); the surviving animals were smaller than their wild-type littermates, had dilated hearts, and showed overt signs of heart failure. 24186210 8 61 theme Several 1114:1120 arg1 genes 1133:1137 Several glycolytic genes 1114:1137 Several glycolytic genes 1114:1137 Several glycolytic genes were also upregulated; however, there were no gross changes in mitochondrial O2 consumption. 24186210 0 62 theme postnatal 35:43 arg1 viability 45:53 postnatal viability 35:53 postnatal viability 35:53 Cardiomyocyte Ogt is essential for postnatal viability. 24186210 8 63 theme gross 1185:1189 arg1 changes 1191:1197 no gross changes 1182:1197 no gross changes 1182:1197 Several glycolytic genes were also upregulated; however, there were no gross changes in mitochondrial O2 consumption. 24186210 2 64 theme mature 242:247 arg1 cells 249:253 mature cells 242:253 mature cells 242:253 In mature cells, this enzyme catalyzes the posttranslational modification known as O-GlcNAc to various cellular proteins. 24186210 5 65 theme Ogt 697:699 arg1 involvement 668:678 the potential involvement 654:678 the potential involvement of cardiomyocyte Ogt in cardiac maturation 654:721 Presently, we sought to establish the potential involvement of cardiomyocyte Ogt in cardiac maturation. 24186210 5 66 theme cardiac 704:710 arg1 maturation 712:721 cardiac maturation 704:721 cardiac maturation 704:721 Presently, we sought to establish the potential involvement of cardiomyocyte Ogt in cardiac maturation. 24186210 1 67 theme embryonic 187:195 arg1 viability 207:215 embryonic stem cell viability 187:215 embryonic stem cell viability 187:215 The singly coded gene O-linked-β-N-acetylglucosamine (O-GlcNAc) transferase (Ogt) resides on the X chromosome and is necessary for embryonic stem cell viability during embryogenesis. 24186210 1 68 theme coded 67:71 arg1 Ogt 133:135 Ogt 133:135 Ogt 133:135 The singly coded gene O-linked-β-N-acetylglucosamine (O-GlcNAc) transferase (Ogt) resides on the X chromosome and is necessary for embryonic stem cell viability during embryogenesis. 24186210 1 68 theme coded 67:71 arg1 transferase 120:130 The singly coded gene O-linked-β-N-acetylglucosamine (O-GlcNAc) transferase 56:130 The singly coded gene O-linked-β-N-acetylglucosamine (O-GlcNAc) transferase (Ogt) 56:136 The singly coded gene O-linked-β-N-acetylglucosamine (O-GlcNAc) transferase (Ogt) resides on the X chromosome and is necessary for embryonic stem cell viability during embryogenesis. 24186210 1 68 theme coded 67:71 arg1 necessary 173:181 necessary 173:181 necessary 173:181 The singly coded gene O-linked-β-N-acetylglucosamine (O-GlcNAc) transferase (Ogt) resides on the X chromosome and is necessary for embryonic stem cell viability during embryogenesis. 24186210 3 69 theme protein 431:437 arg1 O-GlcNAcylation 439:453 protein O-GlcNAcylation 431:453 protein O-GlcNAcylation 431:453 Several groups, including our own, have shown that acute increases in protein O-GlcNAcylation are cardioprotective both in vitro and in vivo. 24186210 12 70 theme inducible 1801:1809 arg1 deletion 1811:1818 inducible deletion 1801:1818 inducible deletion of cmOGT in the adult mouse 1801:1846 Thus, cardiomyocyte Ogt is necessary for maturation of the mammalian heart, and inducible deletion of cmOGT in the adult mouse produces progressive ventricular dysfunction. 24186210 1 71 theme O-linked-β-N-acetylglucosamine 78:107 arg1 Ogt 133:135 Ogt 133:135 Ogt 133:135 The singly coded gene O-linked-β-N-acetylglucosamine (O-GlcNAc) transferase (Ogt) resides on the X chromosome and is necessary for embryonic stem cell viability during embryogenesis. 24186210 1 71 theme O-linked-β-N-acetylglucosamine 78:107 arg1 transferase 120:130 The singly coded gene O-linked-β-N-acetylglucosamine (O-GlcNAc) transferase 56:130 The singly coded gene O-linked-β-N-acetylglucosamine (O-GlcNAc) transferase (Ogt) 56:136 The singly coded gene O-linked-β-N-acetylglucosamine (O-GlcNAc) transferase (Ogt) resides on the X chromosome and is necessary for embryonic stem cell viability during embryogenesis. 24186210 1 71 theme O-linked-β-N-acetylglucosamine 78:107 arg1 necessary 173:181 necessary 173:181 necessary 173:181 The singly coded gene O-linked-β-N-acetylglucosamine (O-GlcNAc) transferase (Ogt) resides on the X chromosome and is necessary for embryonic stem cell viability during embryogenesis. 24186210 6 72 theme KO 798:799 arg1 mouse 814:818 a constitutive cardiomyocyte-specific (cm)OGT KO (c-cmOGT KO) mouse 752:818 a constitutive cardiomyocyte-specific (cm)OGT KO (c-cmOGT KO) mouse 752:818 Initially, we characterized a constitutive cardiomyocyte-specific (cm)OGT KO (c-cmOGT KO) mouse and found that only 12% of the c-cmOGT KO mice survived to weaning age (4 wk old); the surviving animals were smaller than their wild-type littermates, had dilated hearts, and showed overt signs of heart failure. 24186210 1 73 theme O-GlcNAc 110:117 arg1 Ogt 133:135 Ogt 133:135 Ogt 133:135 The singly coded gene O-linked-β-N-acetylglucosamine (O-GlcNAc) transferase (Ogt) resides on the X chromosome and is necessary for embryonic stem cell viability during embryogenesis. 24186210 1 73 theme O-GlcNAc 110:117 arg1 transferase 120:130 The singly coded gene O-linked-β-N-acetylglucosamine (O-GlcNAc) transferase 56:130 The singly coded gene O-linked-β-N-acetylglucosamine (O-GlcNAc) transferase (Ogt) 56:136 The singly coded gene O-linked-β-N-acetylglucosamine (O-GlcNAc) transferase (Ogt) resides on the X chromosome and is necessary for embryonic stem cell viability during embryogenesis. 24186210 1 73 theme O-GlcNAc 110:117 arg1 necessary 173:181 necessary 173:181 necessary 173:181 The singly coded gene O-linked-β-N-acetylglucosamine (O-GlcNAc) transferase (Ogt) resides on the X chromosome and is necessary for embryonic stem cell viability during embryogenesis. 24186210 4 74 theme cardiac 546:552 arg1 function 554:561 cardiac function 546:561 cardiac function 546:561 Yet, little is known about how OGT affects cardiac function because total body knockout (KO) animals are not viable. 24186210 7 75 theme c-cmOGT 1047:1053 arg1 hearts 1058:1063 Dysfunctional c-cmOGT KO hearts 1033:1063 Dysfunctional c-cmOGT KO hearts 1033:1063 Dysfunctional c-cmOGT KO hearts were more fibrotic, apoptotic, and hypertrophic. 24186210 12 76 theme mammalian 1780:1788 arg1 heart 1790:1794 the mammalian heart 1776:1794 the mammalian heart 1776:1794 Thus, cardiomyocyte Ogt is necessary for maturation of the mammalian heart, and inducible deletion of cmOGT in the adult mouse produces progressive ventricular dysfunction. 24186210 1 77 theme stem 197:200 arg1 viability 207:215 embryonic stem cell viability 187:215 embryonic stem cell viability 187:215 The singly coded gene O-linked-β-N-acetylglucosamine (O-GlcNAc) transferase (Ogt) resides on the X chromosome and is necessary for embryonic stem cell viability during embryogenesis. 24186210 9 78 theme hearts 1257:1262 arg1 Histopathology 1232:1245 Histopathology 1232:1245 Histopathology of the KO hearts 1232:1262 Histopathology of the KO hearts indicated the potential involvement of endoplasmic reticulum stress, directing us to evaluate expression of 78-kDa glucose-regulated protein and protein disulfide isomerase, which were elevated. 24186210 6 79 theme failure 1024:1030 arg1 signs 1009:1013 overt signs 1003:1013 overt signs of heart failure 1003:1030 Initially, we characterized a constitutive cardiomyocyte-specific (cm)OGT KO (c-cmOGT KO) mouse and found that only 12% of the c-cmOGT KO mice survived to weaning age (4 wk old); the surviving animals were smaller than their wild-type littermates, had dilated hearts, and showed overt signs of heart failure. 24186210 11 80 theme long-term 1623:1631 arg1 loss 1633:1636 long-term loss 1623:1636 long-term loss (via inducible deletion) of cmOGT 1623:1670 Yet, long-term loss (via inducible deletion) of cmOGT produced gradual and progressive cardiomyopathy. 24186210 10 81 theme deletion 1608:1615 arg1 weeks 1599:1603 weeks 1599:1603 weeks of deletion 1599:1615 Additional groups of mice were subjected to inducible deletion of cmOGT, which did not produce overt dysfunction within the first couple of weeks of deletion. 24186210 6 82 theme c-cmOGT 802:808 arg1 mouse 814:818 a constitutive cardiomyocyte-specific (cm)OGT KO (c-cmOGT KO) mouse 752:818 a constitutive cardiomyocyte-specific (cm)OGT KO (c-cmOGT KO) mouse 752:818 Initially, we characterized a constitutive cardiomyocyte-specific (cm)OGT KO (c-cmOGT KO) mouse and found that only 12% of the c-cmOGT KO mice survived to weaning age (4 wk old); the surviving animals were smaller than their wild-type littermates, had dilated hearts, and showed overt signs of heart failure. 24186210 10 83 theme weeks 1599:1603 arg1 first 1583:1587 first 1583:1587 first 1583:1587 Additional groups of mice were subjected to inducible deletion of cmOGT, which did not produce overt dysfunction within the first couple of weeks of deletion. 24186210 9 84 theme protein 1397:1403 arg1 expression 1358:1367 expression 1358:1367 expression of 78-kDa glucose-regulated protein and protein disulfide isomerase, which were elevated 1358:1456 Histopathology of the KO hearts indicated the potential involvement of endoplasmic reticulum stress, directing us to evaluate expression of 78-kDa glucose-regulated protein and protein disulfide isomerase, which were elevated. 24186210 6 85 theme overt 1003:1007 arg1 signs 1009:1013 overt signs 1003:1013 overt signs of heart failure 1003:1030 Initially, we characterized a constitutive cardiomyocyte-specific (cm)OGT KO (c-cmOGT KO) mouse and found that only 12% of the c-cmOGT KO mice survived to weaning age (4 wk old); the surviving animals were smaller than their wild-type littermates, had dilated hearts, and showed overt signs of heart failure. 24186210 9 86 theme endoplasmic 1303:1313 arg1 reticulum 1315:1323 endoplasmic reticulum 1303:1323 endoplasmic reticulum stress 1303:1330 Histopathology of the KO hearts indicated the potential involvement of endoplasmic reticulum stress, directing us to evaluate expression of 78-kDa glucose-regulated protein and protein disulfide isomerase, which were elevated. 26527687 0 0 theme O-GlcNAcase 92:102 arg1 Expression 104:113 O-GlcNAcase Expression 92:113 O-GlcNAcase Expression 92:113 E2F1 Transcription Factor Regulates O-linked N-acetylglucosamine (O-GlcNAc) Transferase and O-GlcNAcase Expression. 26527687 10 1 theme mouse 1389:1393 arg1 fibroblasts 1405:1415 Rb1-deficient mouse embryonic fibroblasts 1375:1415 Rb1-deficient mouse embryonic fibroblasts 1375:1415 Rb1-deficient mouse embryonic fibroblasts showed increased levels of Ogt and Mgea5 expression, yet overexpression of E2F1 in the Rb1-deficient cells did not alter Ogt and Mgea5 expression, suggesting that Rb1 is required for E2F1-mediated suppression. 26527687 4 2 theme OGA 858:860 arg1 protein 862:868 OGA protein 858:868 OGA protein 858:868 Here, we used a reporter-based assay to analyze minimal promoters and leveraged in silico modeling to nominate several candidate transcription factor binding sites in both Ogt (i.e. the gene for OGT protein) and Mgea5 (i.e. the gene for OGA protein). 26527687 2 3 theme OGT/OGA 347:353 arg1 expression 363:372 OGT/OGA protein expression 347:372 OGT/OGA protein expression 347:372 Until recently, it was assumed that OGT/OGA protein expression was relatively constant. 26527687 1 4 theme important 232:240 arg1 modification 260:271 an important posttranslational modification 229:271 an important posttranslational modification that may factor in multiple diseases 229:308 Protein O-GlcNAcylation, which is controlled by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), has emerged as an important posttranslational modification that may factor in multiple diseases. 26527687 4 5 dep gene 849:852 arg1 i.e. 840:843 i.e. 840:843 i.e. 840:843 Here, we used a reporter-based assay to analyze minimal promoters and leveraged in silico modeling to nominate several candidate transcription factor binding sites in both Ogt (i.e. the gene for OGT protein) and Mgea5 (i.e. the gene for OGA protein). 26527687 8 6 contain had 1234:1236 arg1 fibroblasts 1222:1232 E2F1-deficient mouse fibroblasts 1201:1232 E2F1-deficient mouse fibroblasts 1201:1232 Conversely, E2F1-deficient mouse fibroblasts had increased Ogt and Mgea5 expression. 26527687 8 6 contain had 1234:1236 arg2 expression 1262:1271 increased Ogt and Mgea5 expression 1238:1271 increased Ogt and Mgea5 expression 1238:1271 Conversely, E2F1-deficient mouse fibroblasts had increased Ogt and Mgea5 expression. 26527687 4 7 from sites 779:783 arg1 Ogt 793:795 Ogt 793:795 Ogt (i.e. the gene for OGT protein) 793:827 Here, we used a reporter-based assay to analyze minimal promoters and leveraged in silico modeling to nominate several candidate transcription factor binding sites in both Ogt (i.e. the gene for OGT protein) and Mgea5 (i.e. the gene for OGA protein). 26527687 4 7 from sites 779:783 arg1 Mgea5 833:837 Mgea5 833:837 Mgea5 (i.e. the gene for OGA protein) 833:869 Here, we used a reporter-based assay to analyze minimal promoters and leveraged in silico modeling to nominate several candidate transcription factor binding sites in both Ogt (i.e. the gene for OGT protein) and Mgea5 (i.e. the gene for OGA protein). 26527687 1 8 theme posttranslational 242:258 arg1 modification 260:271 an important posttranslational modification 229:271 an important posttranslational modification that may factor in multiple diseases 229:308 Protein O-GlcNAcylation, which is controlled by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), has emerged as an important posttranslational modification that may factor in multiple diseases. 26527687 11 9 theme promoter 1689:1696 arg1 elements 1698:1705 the promoter elements 1685:1705 the promoter elements for mouse Ogt and Mgea5 genes 1685:1735 In conclusion, this work identifies and validates some of the promoter elements for mouse Ogt and Mgea5 genes. 26527687 10 10 theme Mgea5 1452:1456 arg1 expression 1458:1467 Mgea5 expression 1452:1467 Mgea5 expression 1452:1467 Rb1-deficient mouse embryonic fibroblasts showed increased levels of Ogt and Mgea5 expression, yet overexpression of E2F1 in the Rb1-deficient cells did not alter Ogt and Mgea5 expression, suggesting that Rb1 is required for E2F1-mediated suppression. 26527687 4 11 theme factor 764:769 arg1 sites 779:783 nominate several candidate transcription factor binding sites 723:783 nominate several candidate transcription factor binding sites in both Ogt (i.e. the gene for OGT protein) and Mgea5 (i.e. the gene for OGA protein) 723:869 Here, we used a reporter-based assay to analyze minimal promoters and leveraged in silico modeling to nominate several candidate transcription factor binding sites in both Ogt (i.e. the gene for OGT protein) and Mgea5 (i.e. the gene for OGA protein). 26527687 5 12 theme site 902:905 arg1 sequences 917:925 multiple E2F binding site consensus sequences 881:925 multiple E2F binding site consensus sequences 881:925 We noted multiple E2F binding site consensus sequences in both promoters. 26527687 5 13 theme multiple 881:888 arg1 sequences 917:925 multiple E2F binding site consensus sequences 881:925 multiple E2F binding site consensus sequences 881:925 We noted multiple E2F binding site consensus sequences in both promoters. 26527687 3 14 theme trans 529:533 arg1 elements 535:542 the cis and trans elements 517:542 the cis and trans elements that regulate the expression of these enzymes 517:588 Several groups, including ours, have shown that OGT and/or OGA expression changes in several pathologic contexts, yet the cis and trans elements that regulate the expression of these enzymes remain essentially unexplored. 26527687 3 15 theme pathologic 492:501 arg1 contexts 503:510 several pathologic contexts 484:510 several pathologic contexts 484:510 Several groups, including ours, have shown that OGT and/or OGA expression changes in several pathologic contexts, yet the cis and trans elements that regulate the expression of these enzymes remain essentially unexplored. 26527687 4 16 dep in 701:702 arg1 silico 704:709 silico 704:709 silico 704:709 Here, we used a reporter-based assay to analyze minimal promoters and leveraged in silico modeling to nominate several candidate transcription factor binding sites in both Ogt (i.e. the gene for OGT protein) and Mgea5 (i.e. the gene for OGA protein). 26527687 10 17 theme Rb1-deficient 1504:1516 arg1 cells 1518:1522 the Rb1-deficient cells 1500:1522 the Rb1-deficient cells 1500:1522 Rb1-deficient mouse embryonic fibroblasts showed increased levels of Ogt and Mgea5 expression, yet overexpression of E2F1 in the Rb1-deficient cells did not alter Ogt and Mgea5 expression, suggesting that Rb1 is required for E2F1-mediated suppression. 26527687 8 18 theme Ogt 1248:1250 arg1 expression 1262:1271 increased Ogt and Mgea5 expression 1238:1271 increased Ogt and Mgea5 expression 1238:1271 Conversely, E2F1-deficient mouse fibroblasts had increased Ogt and Mgea5 expression. 26527687 10 19 theme increased 1424:1432 arg1 levels 1434:1439 increased levels 1424:1439 increased levels of Ogt 1424:1446 Rb1-deficient mouse embryonic fibroblasts showed increased levels of Ogt and Mgea5 expression, yet overexpression of E2F1 in the Rb1-deficient cells did not alter Ogt and Mgea5 expression, suggesting that Rb1 is required for E2F1-mediated suppression. 26527687 4 20 dep gene 807:810 arg1 i.e. 798:801 i.e. 798:801 i.e. 798:801 Here, we used a reporter-based assay to analyze minimal promoters and leveraged in silico modeling to nominate several candidate transcription factor binding sites in both Ogt (i.e. the gene for OGT protein) and Mgea5 (i.e. the gene for OGA protein). 26527687 6 21 dep cells 1013:1017 arg1 mouse 1007:1011 mouse 1007:1011 mouse 1007:1011 We performed chromatin immunoprecipitation in both human and mouse cells and found that E2F1 bound to candidate E2F binding sites in both promoters. 26527687 6 21 dep cells 1013:1017 arg1 both 992:995 both 992:995 both 992:995 We performed chromatin immunoprecipitation in both human and mouse cells and found that E2F1 bound to candidate E2F binding sites in both promoters. 26527687 4 22 theme reporter-based 637:650 arg1 assay 652:656 a reporter-based assay 635:656 a reporter-based assay 635:656 Here, we used a reporter-based assay to analyze minimal promoters and leveraged in silico modeling to nominate several candidate transcription factor binding sites in both Ogt (i.e. the gene for OGT protein) and Mgea5 (i.e. the gene for OGA protein). 26527687 10 23 theme Mgea5 1546:1550 arg1 expression 1552:1561 Mgea5 expression 1546:1561 Mgea5 expression 1546:1561 Rb1-deficient mouse embryonic fibroblasts showed increased levels of Ogt and Mgea5 expression, yet overexpression of E2F1 in the Rb1-deficient cells did not alter Ogt and Mgea5 expression, suggesting that Rb1 is required for E2F1-mediated suppression. 26527687 6 24 dep both 992:995 arg1 human 997:1001 human 997:1001 human 997:1001 We performed chromatin immunoprecipitation in both human and mouse cells and found that E2F1 bound to candidate E2F binding sites in both promoters. 26527687 4 25 theme OGT 816:818 arg1 protein 820:826 OGT protein 816:826 OGT protein 816:826 Here, we used a reporter-based assay to analyze minimal promoters and leveraged in silico modeling to nominate several candidate transcription factor binding sites in both Ogt (i.e. the gene for OGT protein) and Mgea5 (i.e. the gene for OGA protein). 26527687 3 26 theme cis 521:523 arg1 elements 535:542 the cis and trans elements 517:542 the cis and trans elements that regulate the expression of these enzymes 517:588 Several groups, including ours, have shown that OGT and/or OGA expression changes in several pathologic contexts, yet the cis and trans elements that regulate the expression of these enzymes remain essentially unexplored. 26527687 4 27 dep Ogt 793:795 arg1 gene 807:810 the gene 803:810 the gene for OGT protein 803:826 Here, we used a reporter-based assay to analyze minimal promoters and leveraged in silico modeling to nominate several candidate transcription factor binding sites in both Ogt (i.e. the gene for OGT protein) and Mgea5 (i.e. the gene for OGA protein). 26527687 0 28 theme Transcription 5:17 arg1 Factor 19:24 E2F1 Transcription Factor 0:24 E2F1 Transcription Factor 0:24 E2F1 Transcription Factor Regulates O-linked N-acetylglucosamine (O-GlcNAc) Transferase and O-GlcNAcase Expression. 26527687 11 29 theme Mgea5 1725:1729 arg1 genes 1731:1735 Mgea5 genes 1725:1735 Mgea5 genes 1725:1735 In conclusion, this work identifies and validates some of the promoter elements for mouse Ogt and Mgea5 genes. 26527687 3 30 from changes 473:479 arg1 contexts 503:510 several pathologic contexts 484:510 several pathologic contexts 484:510 Several groups, including ours, have shown that OGT and/or OGA expression changes in several pathologic contexts, yet the cis and trans elements that regulate the expression of these enzymes remain essentially unexplored. 26527687 4 31 theme nominate 723:730 arg1 sites 779:783 nominate several candidate transcription factor binding sites 723:783 nominate several candidate transcription factor binding sites in both Ogt (i.e. the gene for OGT protein) and Mgea5 (i.e. the gene for OGA protein) 723:869 Here, we used a reporter-based assay to analyze minimal promoters and leveraged in silico modeling to nominate several candidate transcription factor binding sites in both Ogt (i.e. the gene for OGT protein) and Mgea5 (i.e. the gene for OGA protein). 26527687 0 32 theme E2F1 0:3 arg1 Factor 19:24 E2F1 Transcription Factor 0:24 E2F1 Transcription Factor 0:24 E2F1 Transcription Factor Regulates O-linked N-acetylglucosamine (O-GlcNAc) Transferase and O-GlcNAcase Expression. 26527687 9 33 theme known 1281:1285 arg1 partners 1295:1302 the known binding partners 1277:1302 the known binding partners for E2F1 1277:1311 Of the known binding partners for E2F1, we queried whether retinoblastoma 1 (Rb1) might be involved. 26527687 1 34 from factor 282:287 arg1 diseases 301:308 multiple diseases 292:308 multiple diseases 292:308 Protein O-GlcNAcylation, which is controlled by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), has emerged as an important posttranslational modification that may factor in multiple diseases. 26527687 5 35 theme E2F 890:892 arg1 sequences 917:925 multiple E2F binding site consensus sequences 881:925 multiple E2F binding site consensus sequences 881:925 We noted multiple E2F binding site consensus sequences in both promoters. 26527687 8 36 theme E2F1-deficient 1201:1214 arg1 fibroblasts 1222:1232 E2F1-deficient mouse fibroblasts 1201:1232 E2F1-deficient mouse fibroblasts 1201:1232 Conversely, E2F1-deficient mouse fibroblasts had increased Ogt and Mgea5 expression. 26527687 10 37 theme Rb1-deficient 1375:1387 arg1 fibroblasts 1405:1415 Rb1-deficient mouse embryonic fibroblasts 1375:1415 Rb1-deficient mouse embryonic fibroblasts 1375:1415 Rb1-deficient mouse embryonic fibroblasts showed increased levels of Ogt and Mgea5 expression, yet overexpression of E2F1 in the Rb1-deficient cells did not alter Ogt and Mgea5 expression, suggesting that Rb1 is required for E2F1-mediated suppression. 26527687 9 38 theme binding 1287:1293 arg1 partners 1295:1302 the known binding partners 1277:1302 the known binding partners for E2F1 1277:1311 Of the known binding partners for E2F1, we queried whether retinoblastoma 1 (Rb1) might be involved. 26527687 0 39 link O-linked 36:43 arg1 N-acetylglucosamine 45:63 O-linked N-acetylglucosamine 36:63 O-linked N-acetylglucosamine (O-GlcNAc) Transferase 36:86 E2F1 Transcription Factor Regulates O-linked N-acetylglucosamine (O-GlcNAc) Transferase and O-GlcNAcase Expression. 26527687 0 39 link O-linked 36:43 arg1 O-GlcNAc 66:73 O-GlcNAc 66:73 O-GlcNAc 66:73 E2F1 Transcription Factor Regulates O-linked N-acetylglucosamine (O-GlcNAc) Transferase and O-GlcNAcase Expression. 26527687 1 40 theme Protein 116:122 arg1 O-GlcNAcylation 124:138 Protein O-GlcNAcylation 116:138 Protein O-GlcNAcylation 116:138 Protein O-GlcNAcylation, which is controlled by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), has emerged as an important posttranslational modification that may factor in multiple diseases. 26527687 10 41 theme embryonic 1395:1403 arg1 fibroblasts 1405:1415 Rb1-deficient mouse embryonic fibroblasts 1375:1415 Rb1-deficient mouse embryonic fibroblasts 1375:1415 Rb1-deficient mouse embryonic fibroblasts showed increased levels of Ogt and Mgea5 expression, yet overexpression of E2F1 in the Rb1-deficient cells did not alter Ogt and Mgea5 expression, suggesting that Rb1 is required for E2F1-mediated suppression. 26527687 8 42 theme mouse 1216:1220 arg1 fibroblasts 1222:1232 E2F1-deficient mouse fibroblasts 1201:1232 E2F1-deficient mouse fibroblasts 1201:1232 Conversely, E2F1-deficient mouse fibroblasts had increased Ogt and Mgea5 expression. 26527687 6 43 theme binding 1062:1068 arg1 sites 1070:1074 candidate E2F binding sites 1048:1074 candidate E2F binding sites in both promoters 1048:1092 We performed chromatin immunoprecipitation in both human and mouse cells and found that E2F1 bound to candidate E2F binding sites in both promoters. 26527687 7 44 dep OGT 1163:1165 arg1 expression 1177:1186 expression 1177:1186 expression 1177:1186 In HEK293 cells, we overexpressed E2F1, which significantly reduced OGT and MGEA5 expression. 26527687 5 45 theme binding 894:900 arg1 sequences 917:925 multiple E2F binding site consensus sequences 881:925 multiple E2F binding site consensus sequences 881:925 We noted multiple E2F binding site consensus sequences in both promoters. 26527687 4 46 theme several 732:738 arg1 sites 779:783 nominate several candidate transcription factor binding sites 723:783 nominate several candidate transcription factor binding sites in both Ogt (i.e. the gene for OGT protein) and Mgea5 (i.e. the gene for OGA protein) 723:869 Here, we used a reporter-based assay to analyze minimal promoters and leveraged in silico modeling to nominate several candidate transcription factor binding sites in both Ogt (i.e. the gene for OGT protein) and Mgea5 (i.e. the gene for OGA protein). 26527687 3 47 theme OGA 458:460 arg1 changes 473:479 OGA expression changes 458:479 OGA expression changes in several pathologic contexts 458:510 Several groups, including ours, have shown that OGT and/or OGA expression changes in several pathologic contexts, yet the cis and trans elements that regulate the expression of these enzymes remain essentially unexplored. 26527687 0 48 theme N-acetylglucosamine 45:63 arg1 Transferase 76:86 O-linked N-acetylglucosamine (O-GlcNAc) Transferase 36:86 O-linked N-acetylglucosamine (O-GlcNAc) Transferase 36:86 E2F1 Transcription Factor Regulates O-linked N-acetylglucosamine (O-GlcNAc) Transferase and O-GlcNAcase Expression. 26527687 1 49 theme multiple 292:299 arg1 diseases 301:308 multiple diseases 292:308 multiple diseases 292:308 Protein O-GlcNAcylation, which is controlled by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), has emerged as an important posttranslational modification that may factor in multiple diseases. 26527687 10 50 from overexpression 1474:1487 arg1 cells 1518:1522 the Rb1-deficient cells 1500:1522 the Rb1-deficient cells 1500:1522 Rb1-deficient mouse embryonic fibroblasts showed increased levels of Ogt and Mgea5 expression, yet overexpression of E2F1 in the Rb1-deficient cells did not alter Ogt and Mgea5 expression, suggesting that Rb1 is required for E2F1-mediated suppression. 26527687 10 51 theme E2F1-mediated 1600:1612 arg1 suppression 1614:1624 E2F1-mediated suppression 1600:1624 E2F1-mediated suppression 1600:1624 Rb1-deficient mouse embryonic fibroblasts showed increased levels of Ogt and Mgea5 expression, yet overexpression of E2F1 in the Rb1-deficient cells did not alter Ogt and Mgea5 expression, suggesting that Rb1 is required for E2F1-mediated suppression. 26527687 0 52 theme O-linked 36:43 arg1 N-acetylglucosamine 45:63 O-linked N-acetylglucosamine 36:63 O-linked N-acetylglucosamine (O-GlcNAc) Transferase 36:86 E2F1 Transcription Factor Regulates O-linked N-acetylglucosamine (O-GlcNAc) Transferase and O-GlcNAcase Expression. 26527687 0 52 theme O-linked 36:43 arg1 O-GlcNAc 66:73 O-GlcNAc 66:73 O-GlcNAc 66:73 E2F1 Transcription Factor Regulates O-linked N-acetylglucosamine (O-GlcNAc) Transferase and O-GlcNAcase Expression. 26527687 12 53 theme protein-dependent 1818:1834 arg1 manner 1836:1841 an Rb1 protein-dependent manner 1811:1841 an Rb1 protein-dependent manner 1811:1841 Specifically, E2F1 negatively regulates both Ogt and Mgea5 expression in an Rb1 protein-dependent manner. 26527687 7 54 theme HEK293 1098:1103 arg1 cells 1105:1109 HEK293 cells 1098:1109 HEK293 cells 1098:1109 In HEK293 cells, we overexpressed E2F1, which significantly reduced OGT and MGEA5 expression. 26527687 4 55 theme transcription 750:762 arg1 sites 779:783 nominate several candidate transcription factor binding sites 723:783 nominate several candidate transcription factor binding sites in both Ogt (i.e. the gene for OGT protein) and Mgea5 (i.e. the gene for OGA protein) 723:869 Here, we used a reporter-based assay to analyze minimal promoters and leveraged in silico modeling to nominate several candidate transcription factor binding sites in both Ogt (i.e. the gene for OGT protein) and Mgea5 (i.e. the gene for OGA protein). 26527687 3 56 theme enzymes 582:588 arg1 expression 562:571 the expression 558:571 the expression of these enzymes 558:588 Several groups, including ours, have shown that OGT and/or OGA expression changes in several pathologic contexts, yet the cis and trans elements that regulate the expression of these enzymes remain essentially unexplored. 26527687 6 57 from sites 1070:1074 arg1 promoters 1084:1092 both promoters 1079:1092 both promoters 1079:1092 We performed chromatin immunoprecipitation in both human and mouse cells and found that E2F1 bound to candidate E2F binding sites in both promoters. 26527687 3 58 theme Several 399:405 arg1 groups 407:412 Several groups 399:412 Several groups 399:412 Several groups, including ours, have shown that OGT and/or OGA expression changes in several pathologic contexts, yet the cis and trans elements that regulate the expression of these enzymes remain essentially unexplored. 26527687 6 59 theme E2F 1058:1060 arg1 sites 1070:1074 candidate E2F binding sites 1048:1074 candidate E2F binding sites in both promoters 1048:1092 We performed chromatin immunoprecipitation in both human and mouse cells and found that E2F1 bound to candidate E2F binding sites in both promoters. 26527687 4 60 theme in 701:702 arg1 modeling 711:718 in silico modeling 701:718 in silico modeling 701:718 Here, we used a reporter-based assay to analyze minimal promoters and leveraged in silico modeling to nominate several candidate transcription factor binding sites in both Ogt (i.e. the gene for OGT protein) and Mgea5 (i.e. the gene for OGA protein). 26527687 4 61 dep Mgea5 833:837 arg1 gene 849:852 the gene 845:852 the gene for OGA protein 845:868 Here, we used a reporter-based assay to analyze minimal promoters and leveraged in silico modeling to nominate several candidate transcription factor binding sites in both Ogt (i.e. the gene for OGT protein) and Mgea5 (i.e. the gene for OGA protein). 26527687 11 62 theme mouse 1711:1715 arg1 Ogt 1717:1719 mouse Ogt 1711:1719 mouse Ogt 1711:1719 In conclusion, this work identifies and validates some of the promoter elements for mouse Ogt and Mgea5 genes. 26527687 12 63 theme Rb1 1814:1816 arg1 manner 1836:1841 an Rb1 protein-dependent manner 1811:1841 an Rb1 protein-dependent manner 1811:1841 Specifically, E2F1 negatively regulates both Ogt and Mgea5 expression in an Rb1 protein-dependent manner. 26527687 3 64 theme several 484:490 arg1 contexts 503:510 several pathologic contexts 484:510 several pathologic contexts 484:510 Several groups, including ours, have shown that OGT and/or OGA expression changes in several pathologic contexts, yet the cis and trans elements that regulate the expression of these enzymes remain essentially unexplored. 26527687 3 65 theme expression 462:471 arg1 changes 473:479 OGA expression changes 458:479 OGA expression changes in several pathologic contexts 458:510 Several groups, including ours, have shown that OGT and/or OGA expression changes in several pathologic contexts, yet the cis and trans elements that regulate the expression of these enzymes remain essentially unexplored. 26527687 4 66 theme candidate 740:748 arg1 sites 779:783 nominate several candidate transcription factor binding sites 723:783 nominate several candidate transcription factor binding sites in both Ogt (i.e. the gene for OGT protein) and Mgea5 (i.e. the gene for OGA protein) 723:869 Here, we used a reporter-based assay to analyze minimal promoters and leveraged in silico modeling to nominate several candidate transcription factor binding sites in both Ogt (i.e. the gene for OGT protein) and Mgea5 (i.e. the gene for OGA protein). 26527687 4 67 theme binding 771:777 arg1 sites 779:783 nominate several candidate transcription factor binding sites 723:783 nominate several candidate transcription factor binding sites in both Ogt (i.e. the gene for OGT protein) and Mgea5 (i.e. the gene for OGA protein) 723:869 Here, we used a reporter-based assay to analyze minimal promoters and leveraged in silico modeling to nominate several candidate transcription factor binding sites in both Ogt (i.e. the gene for OGT protein) and Mgea5 (i.e. the gene for OGA protein). 26527687 5 68 theme consensus 907:915 arg1 sequences 917:925 multiple E2F binding site consensus sequences 881:925 multiple E2F binding site consensus sequences 881:925 We noted multiple E2F binding site consensus sequences in both promoters. 26527687 1 69 theme O-GlcNAc 164:171 arg1 OGT 186:188 OGT 186:188 OGT 186:188 Protein O-GlcNAcylation, which is controlled by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), has emerged as an important posttranslational modification that may factor in multiple diseases. 26527687 1 69 theme O-GlcNAc 164:171 arg1 transferase 173:183 O-GlcNAc transferase 164:183 O-GlcNAc transferase (OGT) 164:189 Protein O-GlcNAcylation, which is controlled by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), has emerged as an important posttranslational modification that may factor in multiple diseases. 26527687 8 70 theme Mgea5 1256:1260 arg1 expression 1262:1271 increased Ogt and Mgea5 expression 1238:1271 increased Ogt and Mgea5 expression 1238:1271 Conversely, E2F1-deficient mouse fibroblasts had increased Ogt and Mgea5 expression. 26527687 10 71 theme Ogt 1444:1446 arg1 expression 1458:1467 Mgea5 expression 1452:1467 Mgea5 expression 1452:1467 Rb1-deficient mouse embryonic fibroblasts showed increased levels of Ogt and Mgea5 expression, yet overexpression of E2F1 in the Rb1-deficient cells did not alter Ogt and Mgea5 expression, suggesting that Rb1 is required for E2F1-mediated suppression. 26527687 10 71 theme Ogt 1444:1446 arg1 levels 1434:1439 increased levels 1424:1439 increased levels of Ogt 1424:1446 Rb1-deficient mouse embryonic fibroblasts showed increased levels of Ogt and Mgea5 expression, yet overexpression of E2F1 in the Rb1-deficient cells did not alter Ogt and Mgea5 expression, suggesting that Rb1 is required for E2F1-mediated suppression. 26527687 6 72 theme candidate 1048:1056 arg1 sites 1070:1074 candidate E2F binding sites 1048:1074 candidate E2F binding sites in both promoters 1048:1092 We performed chromatin immunoprecipitation in both human and mouse cells and found that E2F1 bound to candidate E2F binding sites in both promoters. 26527687 4 73 used used 630:633 arg2 we 627:628 we 627:628 we 627:628 Here, we used a reporter-based assay to analyze minimal promoters and leveraged in silico modeling to nominate several candidate transcription factor binding sites in both Ogt (i.e. the gene for OGT protein) and Mgea5 (i.e. the gene for OGA protein). 26527687 4 74 theme minimal 669:675 arg1 promoters 677:685 minimal promoters 669:685 minimal promoters 669:685 Here, we used a reporter-based assay to analyze minimal promoters and leveraged in silico modeling to nominate several candidate transcription factor binding sites in both Ogt (i.e. the gene for OGT protein) and Mgea5 (i.e. the gene for OGA protein). 26527687 10 75 theme E2F1 1492:1495 arg1 overexpression 1474:1487 overexpression 1474:1487 overexpression of E2F1 in the Rb1-deficient cells 1474:1522 Rb1-deficient mouse embryonic fibroblasts showed increased levels of Ogt and Mgea5 expression, yet overexpression of E2F1 in the Rb1-deficient cells did not alter Ogt and Mgea5 expression, suggesting that Rb1 is required for E2F1-mediated suppression. 26527687 12 76 theme Mgea5 1791:1795 arg1 expression 1797:1806 Mgea5 expression 1791:1806 Mgea5 expression 1791:1806 Specifically, E2F1 negatively regulates both Ogt and Mgea5 expression in an Rb1 protein-dependent manner. 26527687 2 77 theme protein 355:361 arg1 expression 363:372 OGT/OGA protein expression 347:372 OGT/OGA protein expression 347:372 Until recently, it was assumed that OGT/OGA protein expression was relatively constant. 26527687 8 78 theme increased 1238:1246 arg1 expression 1262:1271 increased Ogt and Mgea5 expression 1238:1271 increased Ogt and Mgea5 expression 1238:1271 Conversely, E2F1-deficient mouse fibroblasts had increased Ogt and Mgea5 expression. 26527687 6 79 theme chromatin 959:967 arg1 immunoprecipitation 969:987 chromatin immunoprecipitation 959:987 chromatin immunoprecipitation 959:987 We performed chromatin immunoprecipitation in both human and mouse cells and found that E2F1 bound to candidate E2F binding sites in both promoters. 25498854 12 0 from activity 1454:1461 arg1 kidney 1473:1478 kidney 1473:1478 kidney 1473:1478 Peroxidase and catalase activity in liver, kidney and skeletal muscle were significantly restored besides marked reduction in lipid peroxidation and normalization of hepatic glycogen level in the NOLE treated alloxanized mice. 25498854 12 0 from activity 1454:1461 arg1 muscle 1493:1498 skeletal muscle 1484:1498 skeletal muscle 1484:1498 Peroxidase and catalase activity in liver, kidney and skeletal muscle were significantly restored besides marked reduction in lipid peroxidation and normalization of hepatic glycogen level in the NOLE treated alloxanized mice. 25498854 12 0 from activity 1454:1461 arg1 liver 1466:1470 liver 1466:1470 liver 1466:1470 Peroxidase and catalase activity in liver, kidney and skeletal muscle were significantly restored besides marked reduction in lipid peroxidation and normalization of hepatic glycogen level in the NOLE treated alloxanized mice. 25498854 12 1 theme catalase 1445:1452 arg1 activity 1454:1461 Peroxidase and catalase activity 1430:1461 Peroxidase and catalase activity in liver, kidney and skeletal muscle 1430:1498 Peroxidase and catalase activity in liver, kidney and skeletal muscle were significantly restored besides marked reduction in lipid peroxidation and normalization of hepatic glycogen level in the NOLE treated alloxanized mice. 25498854 6 2 theme oleander 540:547 arg1 NOLE 563:566 NOLE 563:566 NOLE 563:566 MATERIALS AND METHODS Nerium oleander leaf extract (NOLE) was orally administered at 50 and 200mg/kg body weight (BW) dose to alloxanized mice (blood glucose >200mg/dl). 25498854 6 2 theme oleander 540:547 arg1 extract 554:560 MATERIALS AND METHODS Nerium oleander leaf extract 511:560 MATERIALS AND METHODS Nerium oleander leaf extract (NOLE) 511:567 MATERIALS AND METHODS Nerium oleander leaf extract (NOLE) was orally administered at 50 and 200mg/kg body weight (BW) dose to alloxanized mice (blood glucose >200mg/dl). 25498854 3 3 theme odorum 216:221 arg1 Aiton 223:227 Nerium odorum Aiton 209:227 Nerium odorum Aiton 209:227 and Nerium odorum Aiton.) 25498854 8 4 theme phytochemical 940:952 arg1 composition 954:964 the phytochemical composition 936:964 the phytochemical composition of the plant extract 936:985 Furthermore, gas chromatography-mass spectrometry (GC-MS) and high performance liquid chromatography (HPLC) analysis was employed to reveal the phytochemical composition of the plant extract. 25498854 6 5 theme METHODS 525:531 arg1 NOLE 563:566 NOLE 563:566 NOLE 563:566 MATERIALS AND METHODS Nerium oleander leaf extract (NOLE) was orally administered at 50 and 200mg/kg body weight (BW) dose to alloxanized mice (blood glucose >200mg/dl). 25498854 6 5 theme METHODS 525:531 arg1 extract 554:560 MATERIALS AND METHODS Nerium oleander leaf extract 511:560 MATERIALS AND METHODS Nerium oleander leaf extract (NOLE) 511:567 MATERIALS AND METHODS Nerium oleander leaf extract (NOLE) was orally administered at 50 and 200mg/kg body weight (BW) dose to alloxanized mice (blood glucose >200mg/dl). 25498854 6 6 theme MATERIALS 511:519 arg1 NOLE 563:566 NOLE 563:566 NOLE 563:566 MATERIALS AND METHODS Nerium oleander leaf extract (NOLE) was orally administered at 50 and 200mg/kg body weight (BW) dose to alloxanized mice (blood glucose >200mg/dl). 25498854 6 6 theme MATERIALS 511:519 arg1 extract 554:560 MATERIALS AND METHODS Nerium oleander leaf extract 511:560 MATERIALS AND METHODS Nerium oleander leaf extract (NOLE) 511:567 MATERIALS AND METHODS Nerium oleander leaf extract (NOLE) was orally administered at 50 and 200mg/kg body weight (BW) dose to alloxanized mice (blood glucose >200mg/dl). 25498854 12 7 theme Peroxidase 1430:1439 arg1 activity 1454:1461 Peroxidase and catalase activity 1430:1461 Peroxidase and catalase activity in liver, kidney and skeletal muscle 1430:1498 Peroxidase and catalase activity in liver, kidney and skeletal muscle were significantly restored besides marked reduction in lipid peroxidation and normalization of hepatic glycogen level in the NOLE treated alloxanized mice. 25498854 8 8 theme plant 973:977 arg1 extract 979:985 the plant extract 969:985 the plant extract 969:985 Furthermore, gas chromatography-mass spectrometry (GC-MS) and high performance liquid chromatography (HPLC) analysis was employed to reveal the phytochemical composition of the plant extract. 25498854 6 9 theme 50 596:597 arg1 dose 629:632 50 and 200mg/kg body weight (BW) dose 596:632 50 and 200mg/kg body weight (BW) dose 596:632 MATERIALS AND METHODS Nerium oleander leaf extract (NOLE) was orally administered at 50 and 200mg/kg body weight (BW) dose to alloxanized mice (blood glucose >200mg/dl). 25498854 5 10 theme oleander 465:472 arg1 extract 447:453 a standardized hydromethanolic extract 416:453 a standardized hydromethanolic extract of Nerium oleander 416:472 The present study was undertaken to investigate the anti-diabetic capacity of a standardized hydromethanolic extract of Nerium oleander in alloxan induced diabetes in mice. 25498854 12 11 theme NOLE 1626:1629 arg1 mice 1651:1654 the NOLE treated alloxanized mice 1622:1654 the NOLE treated alloxanized mice 1622:1654 Peroxidase and catalase activity in liver, kidney and skeletal muscle were significantly restored besides marked reduction in lipid peroxidation and normalization of hepatic glycogen level in the NOLE treated alloxanized mice. 25498854 11 12 theme potent 1394:1399 arg1 activity 1420:1427 potent antihyperlipidemic activity 1394:1427 potent antihyperlipidemic activity 1394:1427 Percentage decrease in different liver marker enzymes were significant along with decrease in triglyceride and cholesterol levels, displaying potent antihyperlipidemic activity. 25498854 11 13 from decrease 1263:1270 arg1 enzymes 1298:1304 different liver marker enzymes 1275:1304 different liver marker enzymes 1275:1304 Percentage decrease in different liver marker enzymes were significant along with decrease in triglyceride and cholesterol levels, displaying potent antihyperlipidemic activity. 25498854 9 14 theme RESULTS 988:994 arg1 NOLE 996:999 RESULTS NOLE 988:999 RESULTS NOLE 988:999 RESULTS NOLE demonstrated antihyperglycaemic activity by reducing 73.79% blood glucose level after 20 days of treatment. 25498854 1 15 theme ETHNOPHARMACOLOGICAL 128:147 arg1 RELEVANCE 149:157 ETHNOPHARMACOLOGICAL RELEVANCE 128:157 ETHNOPHARMACOLOGICAL RELEVANCE 128:157 ETHNOPHARMACOLOGICAL RELEVANCE Nerium oleander L. (syn. 25498854 12 16 theme glycogen 1604:1611 arg1 level 1613:1617 hepatic glycogen level 1596:1617 hepatic glycogen level 1596:1617 Peroxidase and catalase activity in liver, kidney and skeletal muscle were significantly restored besides marked reduction in lipid peroxidation and normalization of hepatic glycogen level in the NOLE treated alloxanized mice. 25498854 8 17 theme performance 863:873 arg1 HPLC 898:901 HPLC 898:901 HPLC 898:901 Furthermore, gas chromatography-mass spectrometry (GC-MS) and high performance liquid chromatography (HPLC) analysis was employed to reveal the phytochemical composition of the plant extract. 25498854 8 17 theme performance 863:873 arg1 chromatography 882:895 high performance liquid chromatography 858:895 high performance liquid chromatography (HPLC) 858:902 Furthermore, gas chromatography-mass spectrometry (GC-MS) and high performance liquid chromatography (HPLC) analysis was employed to reveal the phytochemical composition of the plant extract. 25498854 12 18 theme lipid 1556:1560 arg1 peroxidation 1562:1573 lipid peroxidation 1556:1573 lipid peroxidation 1556:1573 Peroxidase and catalase activity in liver, kidney and skeletal muscle were significantly restored besides marked reduction in lipid peroxidation and normalization of hepatic glycogen level in the NOLE treated alloxanized mice. 25498854 5 19 dep induced 485:491 arg1 alloxan 477:483 alloxan 477:483 alloxan 477:483 The present study was undertaken to investigate the anti-diabetic capacity of a standardized hydromethanolic extract of Nerium oleander in alloxan induced diabetes in mice. 25498854 10 20 theme 65.72 1197:1201 arg1 % 1202:1202 % 1202:1202 % 1202:1202 Oral glucose tolerance test (OGTT) revealed increase in glucose tolerance as evident by 65.72% decrease in blood glucose in 3h post treatment. 25498854 0 21 theme Nerium 70:75 arg1 oleander 77:84 an ethnopharmacological plant Nerium oleander 40:84 an ethnopharmacological plant Nerium oleander through alloxan 40:100 Assessment of anti-diabetic activity of an ethnopharmacological plant Nerium oleander through alloxan induced diabetes in mice. 25498854 14 22 theme ethnopharmacological 1900:1919 arg1 practices 1921:1929 different ethnopharmacological practices 1890:1929 different ethnopharmacological practices 1890:1929 CONCLUSION The present investigation revealed that Nerium oleander possess potent anti-diabetic activity as claimed in different ethnopharmacological practices. 25498854 8 23 theme chromatography-mass 813:831 arg1 GC-MS 847:851 GC-MS 847:851 GC-MS 847:851 Furthermore, gas chromatography-mass spectrometry (GC-MS) and high performance liquid chromatography (HPLC) analysis was employed to reveal the phytochemical composition of the plant extract. 25498854 8 23 theme chromatography-mass 813:831 arg1 spectrometry 833:844 gas chromatography-mass spectrometry 809:844 gas chromatography-mass spectrometry (GC-MS) 809:852 Furthermore, gas chromatography-mass spectrometry (GC-MS) and high performance liquid chromatography (HPLC) analysis was employed to reveal the phytochemical composition of the plant extract. 25498854 11 24 theme antihyperlipidemic 1401:1418 arg1 activity 1420:1427 potent antihyperlipidemic activity 1394:1427 potent antihyperlipidemic activity 1394:1427 Percentage decrease in different liver marker enzymes were significant along with decrease in triglyceride and cholesterol levels, displaying potent antihyperlipidemic activity. 25498854 6 25 theme weight 617:622 arg1 dose 629:632 50 and 200mg/kg body weight (BW) dose 596:632 50 and 200mg/kg body weight (BW) dose 596:632 MATERIALS AND METHODS Nerium oleander leaf extract (NOLE) was orally administered at 50 and 200mg/kg body weight (BW) dose to alloxanized mice (blood glucose >200mg/dl). 25498854 11 26 from decrease 1334:1341 arg1 levels 1375:1380 triglyceride and cholesterol levels 1346:1380 triglyceride and cholesterol levels 1346:1380 Percentage decrease in different liver marker enzymes were significant along with decrease in triglyceride and cholesterol levels, displaying potent antihyperlipidemic activity. 25498854 10 27 theme blood 1216:1220 arg1 glucose 1222:1228 blood glucose 1216:1228 blood glucose 1216:1228 Oral glucose tolerance test (OGTT) revealed increase in glucose tolerance as evident by 65.72% decrease in blood glucose in 3h post treatment. 25498854 11 28 theme different 1275:1283 arg1 enzymes 1298:1304 different liver marker enzymes 1275:1304 different liver marker enzymes 1275:1304 Percentage decrease in different liver marker enzymes were significant along with decrease in triglyceride and cholesterol levels, displaying potent antihyperlipidemic activity. 25498854 9 29 theme glucose 1067:1073 arg1 level 1075:1079 73.79% blood glucose level 1054:1079 73.79% blood glucose level 1054:1079 RESULTS NOLE demonstrated antihyperglycaemic activity by reducing 73.79% blood glucose level after 20 days of treatment. 25498854 12 30 from reduction 1543:1551 arg1 peroxidation 1562:1573 lipid peroxidation 1556:1573 lipid peroxidation 1556:1573 Peroxidase and catalase activity in liver, kidney and skeletal muscle were significantly restored besides marked reduction in lipid peroxidation and normalization of hepatic glycogen level in the NOLE treated alloxanized mice. 25498854 12 30 from reduction 1543:1551 arg1 mice 1651:1654 the NOLE treated alloxanized mice 1622:1654 the NOLE treated alloxanized mice 1622:1654 Peroxidase and catalase activity in liver, kidney and skeletal muscle were significantly restored besides marked reduction in lipid peroxidation and normalization of hepatic glycogen level in the NOLE treated alloxanized mice. 25498854 8 31 theme high 858:861 arg1 HPLC 898:901 HPLC 898:901 HPLC 898:901 Furthermore, gas chromatography-mass spectrometry (GC-MS) and high performance liquid chromatography (HPLC) analysis was employed to reveal the phytochemical composition of the plant extract. 25498854 8 31 theme high 858:861 arg1 chromatography 882:895 high performance liquid chromatography 858:895 high performance liquid chromatography (HPLC) 858:902 Furthermore, gas chromatography-mass spectrometry (GC-MS) and high performance liquid chromatography (HPLC) analysis was employed to reveal the phytochemical composition of the plant extract. 25498854 3 32 theme Nerium 209:214 arg1 Aiton 223:227 Nerium odorum Aiton 209:227 Nerium odorum Aiton 209:227 and Nerium odorum Aiton.) 25498854 6 33 theme glucose 661:667 arg1 >200mg/dl 669:677 blood glucose >200mg/dl 655:677 blood glucose >200mg/dl 655:677 MATERIALS AND METHODS Nerium oleander leaf extract (NOLE) was orally administered at 50 and 200mg/kg body weight (BW) dose to alloxanized mice (blood glucose >200mg/dl). 25498854 6 33 theme glucose 661:667 arg1 mice 649:652 alloxanized mice 637:652 alloxanized mice (blood glucose >200mg/dl) 637:678 MATERIALS AND METHODS Nerium oleander leaf extract (NOLE) was orally administered at 50 and 200mg/kg body weight (BW) dose to alloxanized mice (blood glucose >200mg/dl). 25498854 10 34 theme tolerance 1122:1130 arg1 OGTT 1138:1141 OGTT 1138:1141 OGTT 1138:1141 Oral glucose tolerance test (OGTT) revealed increase in glucose tolerance as evident by 65.72% decrease in blood glucose in 3h post treatment. 25498854 10 34 theme tolerance 1122:1130 arg1 test 1132:1135 Oral glucose tolerance test 1109:1135 Oral glucose tolerance test (OGTT) 1109:1142 Oral glucose tolerance test (OGTT) revealed increase in glucose tolerance as evident by 65.72% decrease in blood glucose in 3h post treatment. 25498854 8 35 theme liquid 875:880 arg1 HPLC 898:901 HPLC 898:901 HPLC 898:901 Furthermore, gas chromatography-mass spectrometry (GC-MS) and high performance liquid chromatography (HPLC) analysis was employed to reveal the phytochemical composition of the plant extract. 25498854 8 35 theme liquid 875:880 arg1 chromatography 882:895 high performance liquid chromatography 858:895 high performance liquid chromatography (HPLC) 858:902 Furthermore, gas chromatography-mass spectrometry (GC-MS) and high performance liquid chromatography (HPLC) analysis was employed to reveal the phytochemical composition of the plant extract. 25498854 13 36 theme bioactive 1667:1675 arg1 phytocompounds 1677:1690 Different bioactive phytocompounds 1657:1690 Different bioactive phytocompounds with potent anti-diabetic activity 1657:1725 Different bioactive phytocompounds with potent anti-diabetic activity were identified by GC-MS and HPLC analysis. 25498854 0 37 theme anti-diabetic 14:26 arg1 activity 28:35 anti-diabetic activity 14:35 anti-diabetic activity of an ethnopharmacological plant Nerium oleander through alloxan 14:100 Assessment of anti-diabetic activity of an ethnopharmacological plant Nerium oleander through alloxan induced diabetes in mice. 25498854 10 38 theme Oral 1109:1112 arg1 OGTT 1138:1141 OGTT 1138:1141 OGTT 1138:1141 Oral glucose tolerance test (OGTT) revealed increase in glucose tolerance as evident by 65.72% decrease in blood glucose in 3h post treatment. 25498854 10 38 theme Oral 1109:1112 arg1 test 1132:1135 Oral glucose tolerance test 1109:1135 Oral glucose tolerance test (OGTT) 1109:1142 Oral glucose tolerance test (OGTT) revealed increase in glucose tolerance as evident by 65.72% decrease in blood glucose in 3h post treatment. 25498854 9 39 theme treatment 1098:1106 arg1 days 1090:1093 20 days 1087:1093 20 days of treatment 1087:1106 RESULTS NOLE demonstrated antihyperglycaemic activity by reducing 73.79% blood glucose level after 20 days of treatment. 25498854 2 40 theme Nerium 184:189 arg1 Mill 199:202 Nerium indicum Mill 184:202 Nerium indicum Mill. 184:203 Nerium indicum Mill. 25498854 6 41 theme alloxanized 637:647 arg1 >200mg/dl 669:677 blood glucose >200mg/dl 655:677 blood glucose >200mg/dl 655:677 MATERIALS AND METHODS Nerium oleander leaf extract (NOLE) was orally administered at 50 and 200mg/kg body weight (BW) dose to alloxanized mice (blood glucose >200mg/dl). 25498854 6 41 theme alloxanized 637:647 arg1 mice 649:652 alloxanized mice 637:652 alloxanized mice (blood glucose >200mg/dl) 637:678 MATERIALS AND METHODS Nerium oleander leaf extract (NOLE) was orally administered at 50 and 200mg/kg body weight (BW) dose to alloxanized mice (blood glucose >200mg/dl). 25498854 11 42 theme triglyceride 1346:1357 arg1 levels 1375:1380 triglyceride and cholesterol levels 1346:1380 triglyceride and cholesterol levels 1346:1380 Percentage decrease in different liver marker enzymes were significant along with decrease in triglyceride and cholesterol levels, displaying potent antihyperlipidemic activity. 25498854 14 43 theme potent 1846:1851 arg1 activity 1867:1874 potent anti-diabetic activity 1846:1874 potent anti-diabetic activity 1846:1874 CONCLUSION The present investigation revealed that Nerium oleander possess potent anti-diabetic activity as claimed in different ethnopharmacological practices. 25498854 0 44 theme ethnopharmacological 43:62 arg1 oleander 77:84 an ethnopharmacological plant Nerium oleander 40:84 an ethnopharmacological plant Nerium oleander through alloxan 40:100 Assessment of anti-diabetic activity of an ethnopharmacological plant Nerium oleander through alloxan induced diabetes in mice. 25498854 7 45 theme diabetic 729:736 arg1 parameters 738:747 various diabetic parameters 721:747 various diabetic parameters 721:747 After 20 consecutive days of treatment, various diabetic parameters were studied and compared with untreated mice. 25498854 9 46 theme antihyperglycaemic 1014:1031 arg1 activity 1033:1040 antihyperglycaemic activity 1014:1040 antihyperglycaemic activity 1014:1040 RESULTS NOLE demonstrated antihyperglycaemic activity by reducing 73.79% blood glucose level after 20 days of treatment. 25498854 5 47 theme extract 447:453 arg1 capacity 404:411 the anti-diabetic capacity 386:411 the anti-diabetic capacity of a standardized hydromethanolic extract of Nerium oleander in alloxan induced diabetes in mice 386:508 The present study was undertaken to investigate the anti-diabetic capacity of a standardized hydromethanolic extract of Nerium oleander in alloxan induced diabetes in mice. 25498854 10 48 theme glucose 1165:1171 arg1 tolerance 1173:1181 glucose tolerance 1165:1181 glucose tolerance 1165:1181 Oral glucose tolerance test (OGTT) revealed increase in glucose tolerance as evident by 65.72% decrease in blood glucose in 3h post treatment. 25498854 12 49 theme skeletal 1484:1491 arg1 muscle 1493:1498 skeletal muscle 1484:1498 skeletal muscle 1484:1498 Peroxidase and catalase activity in liver, kidney and skeletal muscle were significantly restored besides marked reduction in lipid peroxidation and normalization of hepatic glycogen level in the NOLE treated alloxanized mice. 25498854 11 50 theme cholesterol 1363:1373 arg1 levels 1375:1380 triglyceride and cholesterol levels 1346:1380 triglyceride and cholesterol levels 1346:1380 Percentage decrease in different liver marker enzymes were significant along with decrease in triglyceride and cholesterol levels, displaying potent antihyperlipidemic activity. 25498854 5 51 theme Nerium 458:463 arg1 oleander 465:472 Nerium oleander 458:472 Nerium oleander 458:472 The present study was undertaken to investigate the anti-diabetic capacity of a standardized hydromethanolic extract of Nerium oleander in alloxan induced diabetes in mice. 25498854 5 52 theme anti-diabetic 390:402 arg1 capacity 404:411 the anti-diabetic capacity 386:411 the anti-diabetic capacity of a standardized hydromethanolic extract of Nerium oleander in alloxan induced diabetes in mice 386:508 The present study was undertaken to investigate the anti-diabetic capacity of a standardized hydromethanolic extract of Nerium oleander in alloxan induced diabetes in mice. 25498854 6 53 theme leaf 549:552 arg1 NOLE 563:566 NOLE 563:566 NOLE 563:566 MATERIALS AND METHODS Nerium oleander leaf extract (NOLE) was orally administered at 50 and 200mg/kg body weight (BW) dose to alloxanized mice (blood glucose >200mg/dl). 25498854 6 53 theme leaf 549:552 arg1 extract 554:560 MATERIALS AND METHODS Nerium oleander leaf extract 511:560 MATERIALS AND METHODS Nerium oleander leaf extract (NOLE) 511:567 MATERIALS AND METHODS Nerium oleander leaf extract (NOLE) was orally administered at 50 and 200mg/kg body weight (BW) dose to alloxanized mice (blood glucose >200mg/dl). 25498854 14 54 contain possess 1838:1844 arg2 activity 1867:1874 potent anti-diabetic activity 1846:1874 potent anti-diabetic activity 1846:1874 CONCLUSION The present investigation revealed that Nerium oleander possess potent anti-diabetic activity as claimed in different ethnopharmacological practices. 25498854 14 54 contain possess 1838:1844 arg1 oleander 1829:1836 Nerium oleander 1822:1836 Nerium oleander 1822:1836 CONCLUSION The present investigation revealed that Nerium oleander possess potent anti-diabetic activity as claimed in different ethnopharmacological practices. 25498854 7 55 theme consecutive 690:700 arg1 days 702:705 20 consecutive days 687:705 20 consecutive days of treatment 687:718 After 20 consecutive days of treatment, various diabetic parameters were studied and compared with untreated mice. 25498854 6 56 theme Nerium 533:538 arg1 NOLE 563:566 NOLE 563:566 NOLE 563:566 MATERIALS AND METHODS Nerium oleander leaf extract (NOLE) was orally administered at 50 and 200mg/kg body weight (BW) dose to alloxanized mice (blood glucose >200mg/dl). 25498854 6 56 theme Nerium 533:538 arg1 extract 554:560 MATERIALS AND METHODS Nerium oleander leaf extract 511:560 MATERIALS AND METHODS Nerium oleander leaf extract (NOLE) 511:567 MATERIALS AND METHODS Nerium oleander leaf extract (NOLE) was orally administered at 50 and 200mg/kg body weight (BW) dose to alloxanized mice (blood glucose >200mg/dl). 25498854 5 57 theme standardized 418:429 arg1 extract 447:453 a standardized hydromethanolic extract 416:453 a standardized hydromethanolic extract of Nerium oleander 416:472 The present study was undertaken to investigate the anti-diabetic capacity of a standardized hydromethanolic extract of Nerium oleander in alloxan induced diabetes in mice. 25498854 12 58 theme marked 1536:1541 arg1 reduction 1543:1551 marked reduction 1536:1551 marked reduction in lipid peroxidation 1536:1573 Peroxidase and catalase activity in liver, kidney and skeletal muscle were significantly restored besides marked reduction in lipid peroxidation and normalization of hepatic glycogen level in the NOLE treated alloxanized mice. 25498854 8 59 theme extract 979:985 arg1 composition 954:964 the phytochemical composition 936:964 the phytochemical composition of the plant extract 936:985 Furthermore, gas chromatography-mass spectrometry (GC-MS) and high performance liquid chromatography (HPLC) analysis was employed to reveal the phytochemical composition of the plant extract. 25498854 10 60 from decrease 1204:1211 arg1 glucose 1222:1228 blood glucose 1216:1228 blood glucose 1216:1228 Oral glucose tolerance test (OGTT) revealed increase in glucose tolerance as evident by 65.72% decrease in blood glucose in 3h post treatment. 25498854 10 60 from decrease 1204:1211 arg1 3h 1233:1234 3h 1233:1234 3h post treatment 1233:1249 Oral glucose tolerance test (OGTT) revealed increase in glucose tolerance as evident by 65.72% decrease in blood glucose in 3h post treatment. 25498854 11 61 theme marker 1291:1296 arg1 enzymes 1298:1304 different liver marker enzymes 1275:1304 different liver marker enzymes 1275:1304 Percentage decrease in different liver marker enzymes were significant along with decrease in triglyceride and cholesterol levels, displaying potent antihyperlipidemic activity. 25498854 12 62 theme alloxanized 1639:1649 arg1 mice 1651:1654 the NOLE treated alloxanized mice 1622:1654 the NOLE treated alloxanized mice 1622:1654 Peroxidase and catalase activity in liver, kidney and skeletal muscle were significantly restored besides marked reduction in lipid peroxidation and normalization of hepatic glycogen level in the NOLE treated alloxanized mice. 25498854 10 63 from increase 1153:1160 arg1 tolerance 1173:1181 glucose tolerance 1165:1181 glucose tolerance 1165:1181 Oral glucose tolerance test (OGTT) revealed increase in glucose tolerance as evident by 65.72% decrease in blood glucose in 3h post treatment. 25498854 12 64 theme treated 1631:1637 arg1 mice 1651:1654 the NOLE treated alloxanized mice 1622:1654 the NOLE treated alloxanized mice 1622:1654 Peroxidase and catalase activity in liver, kidney and skeletal muscle were significantly restored besides marked reduction in lipid peroxidation and normalization of hepatic glycogen level in the NOLE treated alloxanized mice. 25498854 9 65 theme 73.79 1054:1058 arg1 % 1059:1059 % 1059:1059 % 1059:1059 RESULTS NOLE demonstrated antihyperglycaemic activity by reducing 73.79% blood glucose level after 20 days of treatment. 25498854 5 66 theme induced 485:491 arg1 diabetes 493:500 alloxan induced diabetes 477:500 alloxan induced diabetes in mice 477:508 The present study was undertaken to investigate the anti-diabetic capacity of a standardized hydromethanolic extract of Nerium oleander in alloxan induced diabetes in mice. 25498854 12 67 theme hepatic 1596:1602 arg1 level 1613:1617 hepatic glycogen level 1596:1617 hepatic glycogen level 1596:1617 Peroxidase and catalase activity in liver, kidney and skeletal muscle were significantly restored besides marked reduction in lipid peroxidation and normalization of hepatic glycogen level in the NOLE treated alloxanized mice. 25498854 13 68 with phytocompounds 1677:1690 arg1 activity 1718:1725 potent anti-diabetic activity 1697:1725 potent anti-diabetic activity 1697:1725 Different bioactive phytocompounds with potent anti-diabetic activity were identified by GC-MS and HPLC analysis. 25498854 12 69 theme level 1613:1617 arg1 reduction 1543:1551 marked reduction 1536:1551 marked reduction in lipid peroxidation 1536:1573 Peroxidase and catalase activity in liver, kidney and skeletal muscle were significantly restored besides marked reduction in lipid peroxidation and normalization of hepatic glycogen level in the NOLE treated alloxanized mice. 25498854 12 69 theme level 1613:1617 arg1 normalization 1579:1591 normalization 1579:1591 normalization of hepatic glycogen level 1579:1617 Peroxidase and catalase activity in liver, kidney and skeletal muscle were significantly restored besides marked reduction in lipid peroxidation and normalization of hepatic glycogen level in the NOLE treated alloxanized mice. 25498854 10 70 theme % 1202:1202 arg1 decrease 1204:1211 65.72% decrease 1197:1211 65.72% decrease in blood glucose in 3h post treatment 1197:1249 Oral glucose tolerance test (OGTT) revealed increase in glucose tolerance as evident by 65.72% decrease in blood glucose in 3h post treatment. 25498854 0 71 theme oleander 77:84 arg1 activity 28:35 anti-diabetic activity 14:35 anti-diabetic activity of an ethnopharmacological plant Nerium oleander through alloxan 14:100 Assessment of anti-diabetic activity of an ethnopharmacological plant Nerium oleander through alloxan induced diabetes in mice. 25498854 9 72 theme % 1059:1059 arg1 level 1075:1079 73.79% blood glucose level 1054:1079 73.79% blood glucose level 1054:1079 RESULTS NOLE demonstrated antihyperglycaemic activity by reducing 73.79% blood glucose level after 20 days of treatment. 25498854 1 73 theme oleander 166:173 arg1 L 175:175 oleander L 166:175 oleander L 166:175 ETHNOPHARMACOLOGICAL RELEVANCE Nerium oleander L. (syn. 25498854 14 74 dep CONCLUSION 1771:1780 arg1 revealed 1808:1815 revealed 1808:1815 revealed that Nerium oleander possess potent anti-diabetic activity as claimed in different ethnopharmacological practices 1808:1929 CONCLUSION The present investigation revealed that Nerium oleander possess potent anti-diabetic activity as claimed in different ethnopharmacological practices. 25498854 12 75 from normalization 1579:1591 arg1 peroxidation 1562:1573 lipid peroxidation 1556:1573 lipid peroxidation 1556:1573 Peroxidase and catalase activity in liver, kidney and skeletal muscle were significantly restored besides marked reduction in lipid peroxidation and normalization of hepatic glycogen level in the NOLE treated alloxanized mice. 25498854 12 75 from normalization 1579:1591 arg1 mice 1651:1654 the NOLE treated alloxanized mice 1622:1654 the NOLE treated alloxanized mice 1622:1654 Peroxidase and catalase activity in liver, kidney and skeletal muscle were significantly restored besides marked reduction in lipid peroxidation and normalization of hepatic glycogen level in the NOLE treated alloxanized mice. 25498854 14 76 theme different 1890:1898 arg1 practices 1921:1929 different ethnopharmacological practices 1890:1929 different ethnopharmacological practices 1890:1929 CONCLUSION The present investigation revealed that Nerium oleander possess potent anti-diabetic activity as claimed in different ethnopharmacological practices. 25498854 8 77 theme gas 809:811 arg1 GC-MS 847:851 GC-MS 847:851 GC-MS 847:851 Furthermore, gas chromatography-mass spectrometry (GC-MS) and high performance liquid chromatography (HPLC) analysis was employed to reveal the phytochemical composition of the plant extract. 25498854 8 77 theme gas 809:811 arg1 spectrometry 833:844 gas chromatography-mass spectrometry 809:844 gas chromatography-mass spectrometry (GC-MS) 809:852 Furthermore, gas chromatography-mass spectrometry (GC-MS) and high performance liquid chromatography (HPLC) analysis was employed to reveal the phytochemical composition of the plant extract. 25498854 5 78 theme present 342:348 arg1 study 350:354 The present study 338:354 The present study 338:354 The present study was undertaken to investigate the anti-diabetic capacity of a standardized hydromethanolic extract of Nerium oleander in alloxan induced diabetes in mice. 25498854 11 79 theme Percentage 1252:1261 arg1 decrease 1263:1270 Percentage decrease 1252:1270 Percentage decrease in different liver marker enzymes 1252:1304 Percentage decrease in different liver marker enzymes were significant along with decrease in triglyceride and cholesterol levels, displaying potent antihyperlipidemic activity. 25498854 6 80 theme body 612:615 arg1 weight 617:622 200mg/kg body weight 603:622 200mg/kg body weight (BW) 603:627 MATERIALS AND METHODS Nerium oleander leaf extract (NOLE) was orally administered at 50 and 200mg/kg body weight (BW) dose to alloxanized mice (blood glucose >200mg/dl). 25498854 6 80 theme body 612:615 arg1 BW 625:626 BW 625:626 BW 625:626 MATERIALS AND METHODS Nerium oleander leaf extract (NOLE) was orally administered at 50 and 200mg/kg body weight (BW) dose to alloxanized mice (blood glucose >200mg/dl). 25498854 8 81 theme spectrometry 833:844 arg1 analysis 904:911 gas chromatography-mass spectrometry (GC-MS) and high performance liquid chromatography (HPLC) analysis 809:911 gas chromatography-mass spectrometry (GC-MS) and high performance liquid chromatography (HPLC) analysis 809:911 Furthermore, gas chromatography-mass spectrometry (GC-MS) and high performance liquid chromatography (HPLC) analysis was employed to reveal the phytochemical composition of the plant extract. 25498854 13 82 theme HPLC 1756:1759 arg1 analysis 1761:1768 HPLC analysis 1756:1768 HPLC analysis 1756:1768 Different bioactive phytocompounds with potent anti-diabetic activity were identified by GC-MS and HPLC analysis. 25498854 1 83 dep Nerium 159:164 arg1 RELEVANCE 149:157 ETHNOPHARMACOLOGICAL RELEVANCE 128:157 ETHNOPHARMACOLOGICAL RELEVANCE 128:157 ETHNOPHARMACOLOGICAL RELEVANCE Nerium oleander L. (syn. 25498854 1 83 dep Nerium 159:164 arg1 L 175:175 oleander L 166:175 oleander L 166:175 ETHNOPHARMACOLOGICAL RELEVANCE Nerium oleander L. (syn. 25498854 1 83 dep Nerium 159:164 arg1 syn 179:181 syn 179:181 syn 179:181 ETHNOPHARMACOLOGICAL RELEVANCE Nerium oleander L. (syn. 25498854 9 84 theme blood 1061:1065 arg1 level 1075:1079 73.79% blood glucose level 1054:1079 73.79% blood glucose level 1054:1079 RESULTS NOLE demonstrated antihyperglycaemic activity by reducing 73.79% blood glucose level after 20 days of treatment. 25498854 5 85 from capacity 404:411 arg1 diabetes 493:500 alloxan induced diabetes 477:500 alloxan induced diabetes in mice 477:508 The present study was undertaken to investigate the anti-diabetic capacity of a standardized hydromethanolic extract of Nerium oleander in alloxan induced diabetes in mice. 25498854 11 86 theme liver 1285:1289 arg1 enzymes 1298:1304 different liver marker enzymes 1275:1304 different liver marker enzymes 1275:1304 Percentage decrease in different liver marker enzymes were significant along with decrease in triglyceride and cholesterol levels, displaying potent antihyperlipidemic activity. 25498854 13 87 theme anti-diabetic 1704:1716 arg1 activity 1718:1725 potent anti-diabetic activity 1697:1725 potent anti-diabetic activity 1697:1725 Different bioactive phytocompounds with potent anti-diabetic activity were identified by GC-MS and HPLC analysis. 25498854 6 88 theme blood 655:659 arg1 >200mg/dl 669:677 blood glucose >200mg/dl 655:677 blood glucose >200mg/dl 655:677 MATERIALS AND METHODS Nerium oleander leaf extract (NOLE) was orally administered at 50 and 200mg/kg body weight (BW) dose to alloxanized mice (blood glucose >200mg/dl). 25498854 6 88 theme blood 655:659 arg1 mice 649:652 alloxanized mice 637:652 alloxanized mice (blood glucose >200mg/dl) 637:678 MATERIALS AND METHODS Nerium oleander leaf extract (NOLE) was orally administered at 50 and 200mg/kg body weight (BW) dose to alloxanized mice (blood glucose >200mg/dl). 25498854 0 89 theme activity 28:35 arg1 Assessment 0:9 Assessment 0:9 Assessment of anti-diabetic activity of an ethnopharmacological plant Nerium oleander through alloxan 0:100 Assessment of anti-diabetic activity of an ethnopharmacological plant Nerium oleander through alloxan induced diabetes in mice. 25498854 7 90 theme untreated 780:788 arg1 mice 790:793 untreated mice 780:793 untreated mice 780:793 After 20 consecutive days of treatment, various diabetic parameters were studied and compared with untreated mice. 25498854 4 91 theme anti-diabetic 247:259 arg1 properties 261:270 its anti-diabetic properties 243:270 its anti-diabetic properties 243:270 is used for its anti-diabetic properties in Pakistan, Algeria, Morocco and is also recognized in Ayurveda. 25498854 2 92 theme indicum 191:197 arg1 Mill 199:202 Nerium indicum Mill 184:202 Nerium indicum Mill. 184:203 Nerium indicum Mill. 25498854 14 93 theme anti-diabetic 1853:1865 arg1 activity 1867:1874 potent anti-diabetic activity 1846:1874 potent anti-diabetic activity 1846:1874 CONCLUSION The present investigation revealed that Nerium oleander possess potent anti-diabetic activity as claimed in different ethnopharmacological practices. 25498854 8 94 theme chromatography 882:895 arg1 analysis 904:911 gas chromatography-mass spectrometry (GC-MS) and high performance liquid chromatography (HPLC) analysis 809:911 gas chromatography-mass spectrometry (GC-MS) and high performance liquid chromatography (HPLC) analysis 809:911 Furthermore, gas chromatography-mass spectrometry (GC-MS) and high performance liquid chromatography (HPLC) analysis was employed to reveal the phytochemical composition of the plant extract. 25498854 13 95 theme potent 1697:1702 arg1 activity 1718:1725 potent anti-diabetic activity 1697:1725 potent anti-diabetic activity 1697:1725 Different bioactive phytocompounds with potent anti-diabetic activity were identified by GC-MS and HPLC analysis. 25498854 10 96 theme glucose 1114:1120 arg1 OGTT 1138:1141 OGTT 1138:1141 OGTT 1138:1141 Oral glucose tolerance test (OGTT) revealed increase in glucose tolerance as evident by 65.72% decrease in blood glucose in 3h post treatment. 25498854 10 96 theme glucose 1114:1120 arg1 test 1132:1135 Oral glucose tolerance test 1109:1135 Oral glucose tolerance test (OGTT) 1109:1142 Oral glucose tolerance test (OGTT) revealed increase in glucose tolerance as evident by 65.72% decrease in blood glucose in 3h post treatment. 25498854 0 97 theme plant 64:68 arg1 oleander 77:84 an ethnopharmacological plant Nerium oleander 40:84 an ethnopharmacological plant Nerium oleander through alloxan 40:100 Assessment of anti-diabetic activity of an ethnopharmacological plant Nerium oleander through alloxan induced diabetes in mice. 25498854 5 98 theme hydromethanolic 431:445 arg1 extract 447:453 a standardized hydromethanolic extract 416:453 a standardized hydromethanolic extract of Nerium oleander 416:472 The present study was undertaken to investigate the anti-diabetic capacity of a standardized hydromethanolic extract of Nerium oleander in alloxan induced diabetes in mice. 25498854 14 99 theme Nerium 1822:1827 arg1 oleander 1829:1836 Nerium oleander 1822:1836 Nerium oleander 1822:1836 CONCLUSION The present investigation revealed that Nerium oleander possess potent anti-diabetic activity as claimed in different ethnopharmacological practices. 25498854 6 100 theme 200mg/kg 603:610 arg1 weight 617:622 200mg/kg body weight 603:622 200mg/kg body weight (BW) 603:627 MATERIALS AND METHODS Nerium oleander leaf extract (NOLE) was orally administered at 50 and 200mg/kg body weight (BW) dose to alloxanized mice (blood glucose >200mg/dl). 25498854 6 100 theme 200mg/kg 603:610 arg1 BW 625:626 BW 625:626 BW 625:626 MATERIALS AND METHODS Nerium oleander leaf extract (NOLE) was orally administered at 50 and 200mg/kg body weight (BW) dose to alloxanized mice (blood glucose >200mg/dl). 25498854 13 101 theme Different 1657:1665 arg1 phytocompounds 1677:1690 Different bioactive phytocompounds 1657:1690 Different bioactive phytocompounds with potent anti-diabetic activity 1657:1725 Different bioactive phytocompounds with potent anti-diabetic activity were identified by GC-MS and HPLC analysis. 25498854 7 102 theme various 721:727 arg1 parameters 738:747 various diabetic parameters 721:747 various diabetic parameters 721:747 After 20 consecutive days of treatment, various diabetic parameters were studied and compared with untreated mice. 25498854 5 103 from diabetes 493:500 arg1 mice 505:508 mice 505:508 mice 505:508 The present study was undertaken to investigate the anti-diabetic capacity of a standardized hydromethanolic extract of Nerium oleander in alloxan induced diabetes in mice. 25498854 14 104 theme present 1786:1792 arg1 investigation 1794:1806 The present investigation 1782:1806 The present investigation 1782:1806 CONCLUSION The present investigation revealed that Nerium oleander possess potent anti-diabetic activity as claimed in different ethnopharmacological practices. 25498854 7 105 theme treatment 710:718 arg1 days 702:705 20 consecutive days 687:705 20 consecutive days of treatment 687:718 After 20 consecutive days of treatment, various diabetic parameters were studied and compared with untreated mice. 28712551 0 0 theme efficient 103:111 arg1 enrichment 113:122 highly efficient enrichment 96:122 highly efficient enrichment of N-linked glycopeptides 96:148 Facile synthesis of thiol-polyethylene glycol functionalized magnetic titania nanomaterials for highly efficient enrichment of N-linked glycopeptides. 28712551 2 1 theme @ 526:526 arg1 PEG 527:529 denoted as Fe3O4@TiO2@PEG 505:529 denoted as Fe3O4@TiO2@PEG 505:529 In this work, by taking advantages of the interaction between titania and thiol groups, thiol-polyethylene glycol functionalized magnetic titania nanomaterials (denoted as Fe3O4@TiO2@PEG) were firstly fabricated as an excellent hydrophilic adsorbent of N-linked glycopeptides. 28712551 2 1 theme @ 526:526 arg1 glycol 451:456 thiol-polyethylene glycol functionalized magnetic titania nanomaterials 432:502 thiol-polyethylene glycol functionalized magnetic titania nanomaterials (denoted as Fe3O4@TiO2@PEG) 432:530 In this work, by taking advantages of the interaction between titania and thiol groups, thiol-polyethylene glycol functionalized magnetic titania nanomaterials (denoted as Fe3O4@TiO2@PEG) were firstly fabricated as an excellent hydrophilic adsorbent of N-linked glycopeptides. 28712551 3 2 theme special 638:644 arg1 interaction 646:656 the special interaction 634:656 the special interaction of titanium-thiol 634:674 On one hand, the special interaction of titanium-thiol makes the synthetic manipulation simple and provides a new idea for design and synthesis of novel nanomaterials; on the other hand, strong magnetic response could realize rapid separation and the outstanding hydrophilicity of polyethylene glycol makes Fe3O4@TiO2@PEG nanomaterials show superior performance for glycopeptides enrichment with ultralow limit of detection (0.1mol/μL) and high selectivity (1:100). 28712551 4 3 theme great 1319:1323 arg1 potential 1325:1333 a great potential 1317:1333 a great potential of Fe3O4@TiO2@PEG nanomaterials for glycoproteomic research 1317:1393 As a result, 24 and 33 glycopeptides enriched from HRP and IgG digests were identified respectively by MALDI-TOF MS, and 300 glycopeptides corresponding to 106 glycoproteins were recognized from merely 2μL human serum, indicating a great potential of Fe3O4@TiO2@PEG nanomaterials for glycoproteomic research. 28712551 3 4 theme Fe3O4 928:932 arg1 TiO2 934:937 Fe3O4@TiO2 928:937 Fe3O4@TiO2@PEG nanomaterials show superior performance for glycopeptides enrichment with ultralow limit of detection (0.1mol/μL) and high selectivity (1:100) 928:1084 On one hand, the special interaction of titanium-thiol makes the synthetic manipulation simple and provides a new idea for design and synthesis of novel nanomaterials; on the other hand, strong magnetic response could realize rapid separation and the outstanding hydrophilicity of polyethylene glycol makes Fe3O4@TiO2@PEG nanomaterials show superior performance for glycopeptides enrichment with ultralow limit of detection (0.1mol/μL) and high selectivity (1:100). 28712551 2 5 theme TiO2 522:525 arg1 PEG 527:529 denoted as Fe3O4@TiO2@PEG 505:529 denoted as Fe3O4@TiO2@PEG 505:529 In this work, by taking advantages of the interaction between titania and thiol groups, thiol-polyethylene glycol functionalized magnetic titania nanomaterials (denoted as Fe3O4@TiO2@PEG) were firstly fabricated as an excellent hydrophilic adsorbent of N-linked glycopeptides. 28712551 2 5 theme TiO2 522:525 arg1 glycol 451:456 thiol-polyethylene glycol functionalized magnetic titania nanomaterials 432:502 thiol-polyethylene glycol functionalized magnetic titania nanomaterials (denoted as Fe3O4@TiO2@PEG) 432:530 In this work, by taking advantages of the interaction between titania and thiol groups, thiol-polyethylene glycol functionalized magnetic titania nanomaterials (denoted as Fe3O4@TiO2@PEG) were firstly fabricated as an excellent hydrophilic adsorbent of N-linked glycopeptides. 28712551 4 6 theme PEG 1349:1351 arg1 nanomaterials 1353:1365 Fe3O4@TiO2@PEG nanomaterials 1338:1365 Fe3O4@TiO2@PEG nanomaterials 1338:1365 As a result, 24 and 33 glycopeptides enriched from HRP and IgG digests were identified respectively by MALDI-TOF MS, and 300 glycopeptides corresponding to 106 glycoproteins were recognized from merely 2μL human serum, indicating a great potential of Fe3O4@TiO2@PEG nanomaterials for glycoproteomic research. 28712551 3 7 theme detection 1035:1043 arg1 limit 1026:1030 ultralow limit 1017:1030 ultralow limit of detection (0.1mol/μL) 1017:1055 On one hand, the special interaction of titanium-thiol makes the synthetic manipulation simple and provides a new idea for design and synthesis of novel nanomaterials; on the other hand, strong magnetic response could realize rapid separation and the outstanding hydrophilicity of polyethylene glycol makes Fe3O4@TiO2@PEG nanomaterials show superior performance for glycopeptides enrichment with ultralow limit of detection (0.1mol/μL) and high selectivity (1:100). 28712551 3 8 theme polyethylene 902:913 arg1 glycol 915:920 polyethylene glycol 902:920 polyethylene glycol 902:920 On one hand, the special interaction of titanium-thiol makes the synthetic manipulation simple and provides a new idea for design and synthesis of novel nanomaterials; on the other hand, strong magnetic response could realize rapid separation and the outstanding hydrophilicity of polyethylene glycol makes Fe3O4@TiO2@PEG nanomaterials show superior performance for glycopeptides enrichment with ultralow limit of detection (0.1mol/μL) and high selectivity (1:100). 28712551 4 9 gly glycopeptides 1212:1224 arg2 glycopeptides 1212:1224 300 glycopeptides 1208:1224 300 glycopeptides corresponding to 106 glycoproteins 1208:1259 As a result, 24 and 33 glycopeptides enriched from HRP and IgG digests were identified respectively by MALDI-TOF MS, and 300 glycopeptides corresponding to 106 glycoproteins were recognized from merely 2μL human serum, indicating a great potential of Fe3O4@TiO2@PEG nanomaterials for glycoproteomic research. 28712551 3 10 theme new 731:733 arg1 idea 735:738 a new idea 729:738 a new idea for design and synthesis of novel nanomaterials 729:786 On one hand, the special interaction of titanium-thiol makes the synthetic manipulation simple and provides a new idea for design and synthesis of novel nanomaterials; on the other hand, strong magnetic response could realize rapid separation and the outstanding hydrophilicity of polyethylene glycol makes Fe3O4@TiO2@PEG nanomaterials show superior performance for glycopeptides enrichment with ultralow limit of detection (0.1mol/μL) and high selectivity (1:100). 28712551 3 11 theme glycol 915:920 arg1 hydrophilicity 884:897 the outstanding hydrophilicity 868:897 the outstanding hydrophilicity of polyethylene glycol 868:920 On one hand, the special interaction of titanium-thiol makes the synthetic manipulation simple and provides a new idea for design and synthesis of novel nanomaterials; on the other hand, strong magnetic response could realize rapid separation and the outstanding hydrophilicity of polyethylene glycol makes Fe3O4@TiO2@PEG nanomaterials show superior performance for glycopeptides enrichment with ultralow limit of detection (0.1mol/μL) and high selectivity (1:100). 28712551 1 12 theme complex 292:298 arg1 samples 311:317 complex biological samples 292:317 complex biological samples for biomarker discovery 292:341 As protein N-glycosylation involved in generation and development of various cancers and diseases, it is vital to capture glycopeptides from complex biological samples for biomarker discovery. 28712551 4 13 theme MALDI-TOF 1190:1198 arg1 MS 1200:1201 MALDI-TOF MS 1190:1201 MALDI-TOF MS 1190:1201 As a result, 24 and 33 glycopeptides enriched from HRP and IgG digests were identified respectively by MALDI-TOF MS, and 300 glycopeptides corresponding to 106 glycoproteins were recognized from merely 2μL human serum, indicating a great potential of Fe3O4@TiO2@PEG nanomaterials for glycoproteomic research. 28712551 4 14 theme @ 1348:1348 arg1 nanomaterials 1353:1365 Fe3O4@TiO2@PEG nanomaterials 1338:1365 Fe3O4@TiO2@PEG nanomaterials 1338:1365 As a result, 24 and 33 glycopeptides enriched from HRP and IgG digests were identified respectively by MALDI-TOF MS, and 300 glycopeptides corresponding to 106 glycoproteins were recognized from merely 2μL human serum, indicating a great potential of Fe3O4@TiO2@PEG nanomaterials for glycoproteomic research. 28712551 3 15 theme @ 938:938 arg1 nanomaterials 943:955 @PEG nanomaterials 938:955 @PEG nanomaterials 938:955 On one hand, the special interaction of titanium-thiol makes the synthetic manipulation simple and provides a new idea for design and synthesis of novel nanomaterials; on the other hand, strong magnetic response could realize rapid separation and the outstanding hydrophilicity of polyethylene glycol makes Fe3O4@TiO2@PEG nanomaterials show superior performance for glycopeptides enrichment with ultralow limit of detection (0.1mol/μL) and high selectivity (1:100). 28712551 1 16 theme biological 300:309 arg1 samples 311:317 complex biological samples 292:317 complex biological samples for biomarker discovery 292:341 As protein N-glycosylation involved in generation and development of various cancers and diseases, it is vital to capture glycopeptides from complex biological samples for biomarker discovery. 28712551 0 17 theme glycopeptides 136:148 arg1 enrichment 113:122 highly efficient enrichment 96:122 highly efficient enrichment of N-linked glycopeptides 96:148 Facile synthesis of thiol-polyethylene glycol functionalized magnetic titania nanomaterials for highly efficient enrichment of N-linked glycopeptides. 28712551 4 18 gly glycopeptides 1110:1122 arg2 result 1092:1097 a result 1090:1097 a result 1090:1097 As a result, 24 and 33 glycopeptides enriched from HRP and IgG digests were identified respectively by MALDI-TOF MS, and 300 glycopeptides corresponding to 106 glycoproteins were recognized from merely 2μL human serum, indicating a great potential of Fe3O4@TiO2@PEG nanomaterials for glycoproteomic research. 28712551 4 18 gly glycopeptides 1110:1122 arg2 glycopeptides 1110:1122 24 and 33 glycopeptides 1100:1122 24 and 33 glycopeptides enriched from HRP and IgG digests 1100:1156 As a result, 24 and 33 glycopeptides enriched from HRP and IgG digests were identified respectively by MALDI-TOF MS, and 300 glycopeptides corresponding to 106 glycoproteins were recognized from merely 2μL human serum, indicating a great potential of Fe3O4@TiO2@PEG nanomaterials for glycoproteomic research. 28712551 3 19 theme superior 962:969 arg1 performance 971:981 superior performance 962:981 superior performance for glycopeptides enrichment with ultralow limit of detection (0.1mol/μL) 962:1055 On one hand, the special interaction of titanium-thiol makes the synthetic manipulation simple and provides a new idea for design and synthesis of novel nanomaterials; on the other hand, strong magnetic response could realize rapid separation and the outstanding hydrophilicity of polyethylene glycol makes Fe3O4@TiO2@PEG nanomaterials show superior performance for glycopeptides enrichment with ultralow limit of detection (0.1mol/μL) and high selectivity (1:100). 28712551 4 20 theme @ 1343:1343 arg1 nanomaterials 1353:1365 Fe3O4@TiO2@PEG nanomaterials 1338:1365 Fe3O4@TiO2@PEG nanomaterials 1338:1365 As a result, 24 and 33 glycopeptides enriched from HRP and IgG digests were identified respectively by MALDI-TOF MS, and 300 glycopeptides corresponding to 106 glycoproteins were recognized from merely 2μL human serum, indicating a great potential of Fe3O4@TiO2@PEG nanomaterials for glycoproteomic research. 28712551 3 21 theme PEG 939:941 arg1 nanomaterials 943:955 @PEG nanomaterials 938:955 @PEG nanomaterials 938:955 On one hand, the special interaction of titanium-thiol makes the synthetic manipulation simple and provides a new idea for design and synthesis of novel nanomaterials; on the other hand, strong magnetic response could realize rapid separation and the outstanding hydrophilicity of polyethylene glycol makes Fe3O4@TiO2@PEG nanomaterials show superior performance for glycopeptides enrichment with ultralow limit of detection (0.1mol/μL) and high selectivity (1:100). 28712551 0 22 theme N-linked 127:134 arg1 glycopeptides 136:148 N-linked glycopeptides 127:148 N-linked glycopeptides 127:148 Facile synthesis of thiol-polyethylene glycol functionalized magnetic titania nanomaterials for highly efficient enrichment of N-linked glycopeptides. 28712551 4 23 theme Fe3O4 1338:1342 arg1 nanomaterials 1353:1365 Fe3O4@TiO2@PEG nanomaterials 1338:1365 Fe3O4@TiO2@PEG nanomaterials 1338:1365 As a result, 24 and 33 glycopeptides enriched from HRP and IgG digests were identified respectively by MALDI-TOF MS, and 300 glycopeptides corresponding to 106 glycoproteins were recognized from merely 2μL human serum, indicating a great potential of Fe3O4@TiO2@PEG nanomaterials for glycoproteomic research. 28712551 3 24 theme @ 933:933 arg1 TiO2 934:937 Fe3O4@TiO2 928:937 Fe3O4@TiO2@PEG nanomaterials show superior performance for glycopeptides enrichment with ultralow limit of detection (0.1mol/μL) and high selectivity (1:100) 928:1084 On one hand, the special interaction of titanium-thiol makes the synthetic manipulation simple and provides a new idea for design and synthesis of novel nanomaterials; on the other hand, strong magnetic response could realize rapid separation and the outstanding hydrophilicity of polyethylene glycol makes Fe3O4@TiO2@PEG nanomaterials show superior performance for glycopeptides enrichment with ultralow limit of detection (0.1mol/μL) and high selectivity (1:100). 28712551 2 25 theme thiol 418:422 arg1 groups 424:429 titania and thiol groups 406:429 groups 424:429 In this work, by taking advantages of the interaction between titania and thiol groups, thiol-polyethylene glycol functionalized magnetic titania nanomaterials (denoted as Fe3O4@TiO2@PEG) were firstly fabricated as an excellent hydrophilic adsorbent of N-linked glycopeptides. 28712551 1 26 from samples 311:317 arg1 glycopeptides 273:285 capture glycopeptides 265:285 capture glycopeptides from complex biological samples for biomarker discovery 265:341 As protein N-glycosylation involved in generation and development of various cancers and diseases, it is vital to capture glycopeptides from complex biological samples for biomarker discovery. 28712551 1 27 gly glycopeptides 273:285 arg1 samples 311:317 complex biological samples 292:317 complex biological samples for biomarker discovery 292:341 As protein N-glycosylation involved in generation and development of various cancers and diseases, it is vital to capture glycopeptides from complex biological samples for biomarker discovery. 28712551 1 27 gly glycopeptides 273:285 arg2 glycopeptides 273:285 capture glycopeptides 265:285 capture glycopeptides from complex biological samples for biomarker discovery 265:341 As protein N-glycosylation involved in generation and development of various cancers and diseases, it is vital to capture glycopeptides from complex biological samples for biomarker discovery. 28712551 4 28 theme IgG 1146:1148 arg1 digests 1150:1156 HRP and IgG digests 1138:1156 HRP and IgG digests 1138:1156 As a result, 24 and 33 glycopeptides enriched from HRP and IgG digests were identified respectively by MALDI-TOF MS, and 300 glycopeptides corresponding to 106 glycoproteins were recognized from merely 2μL human serum, indicating a great potential of Fe3O4@TiO2@PEG nanomaterials for glycoproteomic research. 28712551 1 29 theme various 220:226 arg1 cancers 228:234 various cancers 220:234 various cancers 220:234 As protein N-glycosylation involved in generation and development of various cancers and diseases, it is vital to capture glycopeptides from complex biological samples for biomarker discovery. 28712551 0 30 theme Facile 0:5 arg1 synthesis 7:15 Facile synthesis 0:15 Facile synthesis of thiol-polyethylene glycol 0:44 Facile synthesis of thiol-polyethylene glycol functionalized magnetic titania nanomaterials for highly efficient enrichment of N-linked glycopeptides. 28712551 3 31 theme high 1061:1064 arg1 selectivity 1066:1076 high selectivity 1061:1076 high selectivity (1:100) 1061:1084 On one hand, the special interaction of titanium-thiol makes the synthetic manipulation simple and provides a new idea for design and synthesis of novel nanomaterials; on the other hand, strong magnetic response could realize rapid separation and the outstanding hydrophilicity of polyethylene glycol makes Fe3O4@TiO2@PEG nanomaterials show superior performance for glycopeptides enrichment with ultralow limit of detection (0.1mol/μL) and high selectivity (1:100). 28712551 3 31 theme high 1061:1064 arg1 1:100 1079:1083 1:100 1079:1083 1:100 1079:1083 On one hand, the special interaction of titanium-thiol makes the synthetic manipulation simple and provides a new idea for design and synthesis of novel nanomaterials; on the other hand, strong magnetic response could realize rapid separation and the outstanding hydrophilicity of polyethylene glycol makes Fe3O4@TiO2@PEG nanomaterials show superior performance for glycopeptides enrichment with ultralow limit of detection (0.1mol/μL) and high selectivity (1:100). 28712551 2 32 link N-linked 597:604 arg1 glycopeptides 606:618 N-linked glycopeptides 597:618 N-linked glycopeptides 597:618 In this work, by taking advantages of the interaction between titania and thiol groups, thiol-polyethylene glycol functionalized magnetic titania nanomaterials (denoted as Fe3O4@TiO2@PEG) were firstly fabricated as an excellent hydrophilic adsorbent of N-linked glycopeptides. 28712551 1 33 theme cancers 228:234 arg1 development 205:215 development 205:215 development 205:215 As protein N-glycosylation involved in generation and development of various cancers and diseases, it is vital to capture glycopeptides from complex biological samples for biomarker discovery. 28712551 1 33 theme cancers 228:234 arg1 generation 190:199 generation 190:199 generation 190:199 As protein N-glycosylation involved in generation and development of various cancers and diseases, it is vital to capture glycopeptides from complex biological samples for biomarker discovery. 28712551 0 34 theme thiol-polyethylene 20:37 arg1 glycol 39:44 thiol-polyethylene glycol 20:44 thiol-polyethylene glycol 20:44 Facile synthesis of thiol-polyethylene glycol functionalized magnetic titania nanomaterials for highly efficient enrichment of N-linked glycopeptides. 28712551 3 35 theme rapid 847:851 arg1 separation 853:862 rapid separation 847:862 rapid separation 847:862 On one hand, the special interaction of titanium-thiol makes the synthetic manipulation simple and provides a new idea for design and synthesis of novel nanomaterials; on the other hand, strong magnetic response could realize rapid separation and the outstanding hydrophilicity of polyethylene glycol makes Fe3O4@TiO2@PEG nanomaterials show superior performance for glycopeptides enrichment with ultralow limit of detection (0.1mol/μL) and high selectivity (1:100). 28712551 2 36 theme functionalized 458:471 arg1 nanomaterials 490:502 functionalized magnetic titania nanomaterials 458:502 thiol-polyethylene glycol functionalized magnetic titania nanomaterials (denoted as Fe3O4@TiO2@PEG) 432:530 In this work, by taking advantages of the interaction between titania and thiol groups, thiol-polyethylene glycol functionalized magnetic titania nanomaterials (denoted as Fe3O4@TiO2@PEG) were firstly fabricated as an excellent hydrophilic adsorbent of N-linked glycopeptides. 28712551 2 37 theme magnetic 473:480 arg1 nanomaterials 490:502 functionalized magnetic titania nanomaterials 458:502 thiol-polyethylene glycol functionalized magnetic titania nanomaterials (denoted as Fe3O4@TiO2@PEG) 432:530 In this work, by taking advantages of the interaction between titania and thiol groups, thiol-polyethylene glycol functionalized magnetic titania nanomaterials (denoted as Fe3O4@TiO2@PEG) were firstly fabricated as an excellent hydrophilic adsorbent of N-linked glycopeptides. 28712551 1 38 theme biomarker 323:331 arg1 discovery 333:341 biomarker discovery 323:341 biomarker discovery 323:341 As protein N-glycosylation involved in generation and development of various cancers and diseases, it is vital to capture glycopeptides from complex biological samples for biomarker discovery. 28712551 0 39 gly glycopeptides 136:148 arg2 glycopeptides 136:148 N-linked glycopeptides 127:148 N-linked glycopeptides 127:148 Facile synthesis of thiol-polyethylene glycol functionalized magnetic titania nanomaterials for highly efficient enrichment of N-linked glycopeptides. 28712551 3 40 gly glycopeptides 987:999 arg2 glycopeptides 987:999 glycopeptides 987:999 glycopeptides enrichment with ultralow limit of detection (0.1mol/μL) 987:1055 On one hand, the special interaction of titanium-thiol makes the synthetic manipulation simple and provides a new idea for design and synthesis of novel nanomaterials; on the other hand, strong magnetic response could realize rapid separation and the outstanding hydrophilicity of polyethylene glycol makes Fe3O4@TiO2@PEG nanomaterials show superior performance for glycopeptides enrichment with ultralow limit of detection (0.1mol/μL) and high selectivity (1:100). 28712551 1 41 theme diseases 240:247 arg1 development 205:215 development 205:215 development 205:215 As protein N-glycosylation involved in generation and development of various cancers and diseases, it is vital to capture glycopeptides from complex biological samples for biomarker discovery. 28712551 1 41 theme diseases 240:247 arg1 generation 190:199 generation 190:199 generation 190:199 As protein N-glycosylation involved in generation and development of various cancers and diseases, it is vital to capture glycopeptides from complex biological samples for biomarker discovery. 28712551 2 42 theme @ 521:521 arg1 PEG 527:529 denoted as Fe3O4@TiO2@PEG 505:529 denoted as Fe3O4@TiO2@PEG 505:529 In this work, by taking advantages of the interaction between titania and thiol groups, thiol-polyethylene glycol functionalized magnetic titania nanomaterials (denoted as Fe3O4@TiO2@PEG) were firstly fabricated as an excellent hydrophilic adsorbent of N-linked glycopeptides. 28712551 2 42 theme @ 521:521 arg1 glycol 451:456 thiol-polyethylene glycol functionalized magnetic titania nanomaterials 432:502 thiol-polyethylene glycol functionalized magnetic titania nanomaterials (denoted as Fe3O4@TiO2@PEG) 432:530 In this work, by taking advantages of the interaction between titania and thiol groups, thiol-polyethylene glycol functionalized magnetic titania nanomaterials (denoted as Fe3O4@TiO2@PEG) were firstly fabricated as an excellent hydrophilic adsorbent of N-linked glycopeptides. 28712551 3 43 theme nanomaterials 774:786 arg1 synthesis 755:763 synthesis 755:763 synthesis 755:763 On one hand, the special interaction of titanium-thiol makes the synthetic manipulation simple and provides a new idea for design and synthesis of novel nanomaterials; on the other hand, strong magnetic response could realize rapid separation and the outstanding hydrophilicity of polyethylene glycol makes Fe3O4@TiO2@PEG nanomaterials show superior performance for glycopeptides enrichment with ultralow limit of detection (0.1mol/μL) and high selectivity (1:100). 28712551 3 43 theme nanomaterials 774:786 arg1 design 744:749 design 744:749 design 744:749 On one hand, the special interaction of titanium-thiol makes the synthetic manipulation simple and provides a new idea for design and synthesis of novel nanomaterials; on the other hand, strong magnetic response could realize rapid separation and the outstanding hydrophilicity of polyethylene glycol makes Fe3O4@TiO2@PEG nanomaterials show superior performance for glycopeptides enrichment with ultralow limit of detection (0.1mol/μL) and high selectivity (1:100). 28712551 3 44 theme synthetic 686:694 arg1 manipulation 696:707 the synthetic manipulation 682:707 the synthetic manipulation simple 682:714 On one hand, the special interaction of titanium-thiol makes the synthetic manipulation simple and provides a new idea for design and synthesis of novel nanomaterials; on the other hand, strong magnetic response could realize rapid separation and the outstanding hydrophilicity of polyethylene glycol makes Fe3O4@TiO2@PEG nanomaterials show superior performance for glycopeptides enrichment with ultralow limit of detection (0.1mol/μL) and high selectivity (1:100). 28712551 2 45 theme titania 406:412 arg1 groups 424:429 titania and thiol groups 406:429 groups 424:429 In this work, by taking advantages of the interaction between titania and thiol groups, thiol-polyethylene glycol functionalized magnetic titania nanomaterials (denoted as Fe3O4@TiO2@PEG) were firstly fabricated as an excellent hydrophilic adsorbent of N-linked glycopeptides. 28712551 2 46 theme thiol-polyethylene 432:449 arg1 PEG 527:529 denoted as Fe3O4@TiO2@PEG 505:529 denoted as Fe3O4@TiO2@PEG 505:529 In this work, by taking advantages of the interaction between titania and thiol groups, thiol-polyethylene glycol functionalized magnetic titania nanomaterials (denoted as Fe3O4@TiO2@PEG) were firstly fabricated as an excellent hydrophilic adsorbent of N-linked glycopeptides. 28712551 2 46 theme thiol-polyethylene 432:449 arg1 adsorbent 584:592 adsorbent 584:592 adsorbent 584:592 In this work, by taking advantages of the interaction between titania and thiol groups, thiol-polyethylene glycol functionalized magnetic titania nanomaterials (denoted as Fe3O4@TiO2@PEG) were firstly fabricated as an excellent hydrophilic adsorbent of N-linked glycopeptides. 28712551 2 46 theme thiol-polyethylene 432:449 arg1 glycol 451:456 thiol-polyethylene glycol functionalized magnetic titania nanomaterials 432:502 thiol-polyethylene glycol functionalized magnetic titania nanomaterials (denoted as Fe3O4@TiO2@PEG) 432:530 In this work, by taking advantages of the interaction between titania and thiol groups, thiol-polyethylene glycol functionalized magnetic titania nanomaterials (denoted as Fe3O4@TiO2@PEG) were firstly fabricated as an excellent hydrophilic adsorbent of N-linked glycopeptides. 28712551 0 47 theme glycol 39:44 arg1 synthesis 7:15 Facile synthesis 0:15 Facile synthesis of thiol-polyethylene glycol 0:44 Facile synthesis of thiol-polyethylene glycol functionalized magnetic titania nanomaterials for highly efficient enrichment of N-linked glycopeptides. 28712551 2 48 theme Fe3O4 516:520 arg1 PEG 527:529 denoted as Fe3O4@TiO2@PEG 505:529 denoted as Fe3O4@TiO2@PEG 505:529 In this work, by taking advantages of the interaction between titania and thiol groups, thiol-polyethylene glycol functionalized magnetic titania nanomaterials (denoted as Fe3O4@TiO2@PEG) were firstly fabricated as an excellent hydrophilic adsorbent of N-linked glycopeptides. 28712551 2 48 theme Fe3O4 516:520 arg1 glycol 451:456 thiol-polyethylene glycol functionalized magnetic titania nanomaterials 432:502 thiol-polyethylene glycol functionalized magnetic titania nanomaterials (denoted as Fe3O4@TiO2@PEG) 432:530 In this work, by taking advantages of the interaction between titania and thiol groups, thiol-polyethylene glycol functionalized magnetic titania nanomaterials (denoted as Fe3O4@TiO2@PEG) were firstly fabricated as an excellent hydrophilic adsorbent of N-linked glycopeptides. 28712551 3 49 theme titanium-thiol 661:674 arg1 interaction 646:656 the special interaction 634:656 the special interaction of titanium-thiol 634:674 On one hand, the special interaction of titanium-thiol makes the synthetic manipulation simple and provides a new idea for design and synthesis of novel nanomaterials; on the other hand, strong magnetic response could realize rapid separation and the outstanding hydrophilicity of polyethylene glycol makes Fe3O4@TiO2@PEG nanomaterials show superior performance for glycopeptides enrichment with ultralow limit of detection (0.1mol/μL) and high selectivity (1:100). 28712551 2 50 theme titania 482:488 arg1 nanomaterials 490:502 functionalized magnetic titania nanomaterials 458:502 thiol-polyethylene glycol functionalized magnetic titania nanomaterials (denoted as Fe3O4@TiO2@PEG) 432:530 In this work, by taking advantages of the interaction between titania and thiol groups, thiol-polyethylene glycol functionalized magnetic titania nanomaterials (denoted as Fe3O4@TiO2@PEG) were firstly fabricated as an excellent hydrophilic adsorbent of N-linked glycopeptides. 28712551 3 51 theme enrichment 1001:1010 arg1 glycopeptides 987:999 glycopeptides 987:999 glycopeptides enrichment with ultralow limit of detection (0.1mol/μL) 987:1055 On one hand, the special interaction of titanium-thiol makes the synthetic manipulation simple and provides a new idea for design and synthesis of novel nanomaterials; on the other hand, strong magnetic response could realize rapid separation and the outstanding hydrophilicity of polyethylene glycol makes Fe3O4@TiO2@PEG nanomaterials show superior performance for glycopeptides enrichment with ultralow limit of detection (0.1mol/μL) and high selectivity (1:100). 28712551 4 52 theme glycoproteomic 1371:1384 arg1 research 1386:1393 glycoproteomic research 1371:1393 glycoproteomic research 1371:1393 As a result, 24 and 33 glycopeptides enriched from HRP and IgG digests were identified respectively by MALDI-TOF MS, and 300 glycopeptides corresponding to 106 glycoproteins were recognized from merely 2μL human serum, indicating a great potential of Fe3O4@TiO2@PEG nanomaterials for glycoproteomic research. 28712551 0 53 theme titania 70:76 arg1 nanomaterials 78:90 magnetic titania nanomaterials 61:90 magnetic titania nanomaterials 61:90 Facile synthesis of thiol-polyethylene glycol functionalized magnetic titania nanomaterials for highly efficient enrichment of N-linked glycopeptides. 28712551 4 54 theme HRP 1138:1140 arg1 digests 1150:1156 HRP and IgG digests 1138:1156 HRP and IgG digests 1138:1156 As a result, 24 and 33 glycopeptides enriched from HRP and IgG digests were identified respectively by MALDI-TOF MS, and 300 glycopeptides corresponding to 106 glycoproteins were recognized from merely 2μL human serum, indicating a great potential of Fe3O4@TiO2@PEG nanomaterials for glycoproteomic research. 28712551 4 55 theme nanomaterials 1353:1365 arg1 potential 1325:1333 a great potential 1317:1333 a great potential of Fe3O4@TiO2@PEG nanomaterials for glycoproteomic research 1317:1393 As a result, 24 and 33 glycopeptides enriched from HRP and IgG digests were identified respectively by MALDI-TOF MS, and 300 glycopeptides corresponding to 106 glycoproteins were recognized from merely 2μL human serum, indicating a great potential of Fe3O4@TiO2@PEG nanomaterials for glycoproteomic research. 28712551 3 56 dep TiO2 934:937 arg1 show 957:960 show 957:960 show superior performance for glycopeptides enrichment with ultralow limit of detection (0.1mol/μL) and high selectivity (1:100) 957:1084 On one hand, the special interaction of titanium-thiol makes the synthetic manipulation simple and provides a new idea for design and synthesis of novel nanomaterials; on the other hand, strong magnetic response could realize rapid separation and the outstanding hydrophilicity of polyethylene glycol makes Fe3O4@TiO2@PEG nanomaterials show superior performance for glycopeptides enrichment with ultralow limit of detection (0.1mol/μL) and high selectivity (1:100). 28712551 2 57 gly glycopeptides 606:618 arg2 glycopeptides 606:618 N-linked glycopeptides 597:618 N-linked glycopeptides 597:618 In this work, by taking advantages of the interaction between titania and thiol groups, thiol-polyethylene glycol functionalized magnetic titania nanomaterials (denoted as Fe3O4@TiO2@PEG) were firstly fabricated as an excellent hydrophilic adsorbent of N-linked glycopeptides. 28712551 0 58 theme magnetic 61:68 arg1 nanomaterials 78:90 magnetic titania nanomaterials 61:90 magnetic titania nanomaterials 61:90 Facile synthesis of thiol-polyethylene glycol functionalized magnetic titania nanomaterials for highly efficient enrichment of N-linked glycopeptides. 28712551 2 59 theme glycopeptides 606:618 arg1 adsorbent 584:592 adsorbent 584:592 adsorbent 584:592 In this work, by taking advantages of the interaction between titania and thiol groups, thiol-polyethylene glycol functionalized magnetic titania nanomaterials (denoted as Fe3O4@TiO2@PEG) were firstly fabricated as an excellent hydrophilic adsorbent of N-linked glycopeptides. 28712551 2 59 theme glycopeptides 606:618 arg1 glycol 451:456 thiol-polyethylene glycol functionalized magnetic titania nanomaterials 432:502 thiol-polyethylene glycol functionalized magnetic titania nanomaterials (denoted as Fe3O4@TiO2@PEG) 432:530 In this work, by taking advantages of the interaction between titania and thiol groups, thiol-polyethylene glycol functionalized magnetic titania nanomaterials (denoted as Fe3O4@TiO2@PEG) were firstly fabricated as an excellent hydrophilic adsorbent of N-linked glycopeptides. 28712551 2 60 theme denoted 505:511 arg1 PEG 527:529 denoted as Fe3O4@TiO2@PEG 505:529 denoted as Fe3O4@TiO2@PEG 505:529 In this work, by taking advantages of the interaction between titania and thiol groups, thiol-polyethylene glycol functionalized magnetic titania nanomaterials (denoted as Fe3O4@TiO2@PEG) were firstly fabricated as an excellent hydrophilic adsorbent of N-linked glycopeptides. 28712551 2 60 theme denoted 505:511 arg1 glycol 451:456 thiol-polyethylene glycol functionalized magnetic titania nanomaterials 432:502 thiol-polyethylene glycol functionalized magnetic titania nanomaterials (denoted as Fe3O4@TiO2@PEG) 432:530 In this work, by taking advantages of the interaction between titania and thiol groups, thiol-polyethylene glycol functionalized magnetic titania nanomaterials (denoted as Fe3O4@TiO2@PEG) were firstly fabricated as an excellent hydrophilic adsorbent of N-linked glycopeptides. 28712551 2 61 dep glycol 451:456 arg1 nanomaterials 490:502 functionalized magnetic titania nanomaterials 458:502 thiol-polyethylene glycol functionalized magnetic titania nanomaterials (denoted as Fe3O4@TiO2@PEG) 432:530 In this work, by taking advantages of the interaction between titania and thiol groups, thiol-polyethylene glycol functionalized magnetic titania nanomaterials (denoted as Fe3O4@TiO2@PEG) were firstly fabricated as an excellent hydrophilic adsorbent of N-linked glycopeptides. 28712551 3 62 theme other 796:800 arg1 hand 802:805 the other hand 792:805 the other hand 792:805 On one hand, the special interaction of titanium-thiol makes the synthetic manipulation simple and provides a new idea for design and synthesis of novel nanomaterials; on the other hand, strong magnetic response could realize rapid separation and the outstanding hydrophilicity of polyethylene glycol makes Fe3O4@TiO2@PEG nanomaterials show superior performance for glycopeptides enrichment with ultralow limit of detection (0.1mol/μL) and high selectivity (1:100). 28712551 2 63 theme N-linked 597:604 arg1 glycopeptides 606:618 N-linked glycopeptides 597:618 N-linked glycopeptides 597:618 In this work, by taking advantages of the interaction between titania and thiol groups, thiol-polyethylene glycol functionalized magnetic titania nanomaterials (denoted as Fe3O4@TiO2@PEG) were firstly fabricated as an excellent hydrophilic adsorbent of N-linked glycopeptides. 28712551 1 64 theme protein 154:160 arg1 N-glycosylation 162:176 protein N-glycosylation 154:176 protein N-glycosylation involved in generation and development of various cancers and diseases 154:247 As protein N-glycosylation involved in generation and development of various cancers and diseases, it is vital to capture glycopeptides from complex biological samples for biomarker discovery. 28712551 4 65 theme human 1293:1297 arg1 serum 1299:1303 merely 2μL human serum 1282:1303 merely 2μL human serum 1282:1303 As a result, 24 and 33 glycopeptides enriched from HRP and IgG digests were identified respectively by MALDI-TOF MS, and 300 glycopeptides corresponding to 106 glycoproteins were recognized from merely 2μL human serum, indicating a great potential of Fe3O4@TiO2@PEG nanomaterials for glycoproteomic research. 28712551 3 66 theme novel 768:772 arg1 nanomaterials 774:786 novel nanomaterials 768:786 novel nanomaterials 768:786 On one hand, the special interaction of titanium-thiol makes the synthetic manipulation simple and provides a new idea for design and synthesis of novel nanomaterials; on the other hand, strong magnetic response could realize rapid separation and the outstanding hydrophilicity of polyethylene glycol makes Fe3O4@TiO2@PEG nanomaterials show superior performance for glycopeptides enrichment with ultralow limit of detection (0.1mol/μL) and high selectivity (1:100). 28712551 4 67 gly glycoproteins 1247:1259 arg1 glycoproteins 1247:1259 106 glycoproteins 1243:1259 106 glycoproteins 1243:1259 As a result, 24 and 33 glycopeptides enriched from HRP and IgG digests were identified respectively by MALDI-TOF MS, and 300 glycopeptides corresponding to 106 glycoproteins were recognized from merely 2μL human serum, indicating a great potential of Fe3O4@TiO2@PEG nanomaterials for glycoproteomic research. 28712551 3 68 theme simple 709:714 arg1 manipulation 696:707 the synthetic manipulation 682:707 the synthetic manipulation simple 682:714 On one hand, the special interaction of titanium-thiol makes the synthetic manipulation simple and provides a new idea for design and synthesis of novel nanomaterials; on the other hand, strong magnetic response could realize rapid separation and the outstanding hydrophilicity of polyethylene glycol makes Fe3O4@TiO2@PEG nanomaterials show superior performance for glycopeptides enrichment with ultralow limit of detection (0.1mol/μL) and high selectivity (1:100). 28712551 0 69 link N-linked 127:134 arg1 glycopeptides 136:148 N-linked glycopeptides 127:148 N-linked glycopeptides 127:148 Facile synthesis of thiol-polyethylene glycol functionalized magnetic titania nanomaterials for highly efficient enrichment of N-linked glycopeptides. 28712551 3 70 with enrichment 1001:1010 arg1 limit 1026:1030 ultralow limit 1017:1030 ultralow limit of detection (0.1mol/μL) 1017:1055 On one hand, the special interaction of titanium-thiol makes the synthetic manipulation simple and provides a new idea for design and synthesis of novel nanomaterials; on the other hand, strong magnetic response could realize rapid separation and the outstanding hydrophilicity of polyethylene glycol makes Fe3O4@TiO2@PEG nanomaterials show superior performance for glycopeptides enrichment with ultralow limit of detection (0.1mol/μL) and high selectivity (1:100). 28712551 3 71 theme outstanding 872:882 arg1 hydrophilicity 884:897 the outstanding hydrophilicity 868:897 the outstanding hydrophilicity of polyethylene glycol 868:920 On one hand, the special interaction of titanium-thiol makes the synthetic manipulation simple and provides a new idea for design and synthesis of novel nanomaterials; on the other hand, strong magnetic response could realize rapid separation and the outstanding hydrophilicity of polyethylene glycol makes Fe3O4@TiO2@PEG nanomaterials show superior performance for glycopeptides enrichment with ultralow limit of detection (0.1mol/μL) and high selectivity (1:100). 28712551 3 72 theme strong 808:813 arg1 response 824:831 strong magnetic response 808:831 strong magnetic response 808:831 On one hand, the special interaction of titanium-thiol makes the synthetic manipulation simple and provides a new idea for design and synthesis of novel nanomaterials; on the other hand, strong magnetic response could realize rapid separation and the outstanding hydrophilicity of polyethylene glycol makes Fe3O4@TiO2@PEG nanomaterials show superior performance for glycopeptides enrichment with ultralow limit of detection (0.1mol/μL) and high selectivity (1:100). 28712551 2 73 theme as 513:514 arg1 PEG 527:529 denoted as Fe3O4@TiO2@PEG 505:529 denoted as Fe3O4@TiO2@PEG 505:529 In this work, by taking advantages of the interaction between titania and thiol groups, thiol-polyethylene glycol functionalized magnetic titania nanomaterials (denoted as Fe3O4@TiO2@PEG) were firstly fabricated as an excellent hydrophilic adsorbent of N-linked glycopeptides. 28712551 2 73 theme as 513:514 arg1 glycol 451:456 thiol-polyethylene glycol functionalized magnetic titania nanomaterials 432:502 thiol-polyethylene glycol functionalized magnetic titania nanomaterials (denoted as Fe3O4@TiO2@PEG) 432:530 In this work, by taking advantages of the interaction between titania and thiol groups, thiol-polyethylene glycol functionalized magnetic titania nanomaterials (denoted as Fe3O4@TiO2@PEG) were firstly fabricated as an excellent hydrophilic adsorbent of N-linked glycopeptides. 28712551 4 74 theme TiO2 1344:1347 arg1 nanomaterials 1353:1365 Fe3O4@TiO2@PEG nanomaterials 1338:1365 Fe3O4@TiO2@PEG nanomaterials 1338:1365 As a result, 24 and 33 glycopeptides enriched from HRP and IgG digests were identified respectively by MALDI-TOF MS, and 300 glycopeptides corresponding to 106 glycoproteins were recognized from merely 2μL human serum, indicating a great potential of Fe3O4@TiO2@PEG nanomaterials for glycoproteomic research. 28712551 3 75 theme magnetic 815:822 arg1 response 824:831 strong magnetic response 808:831 strong magnetic response 808:831 On one hand, the special interaction of titanium-thiol makes the synthetic manipulation simple and provides a new idea for design and synthesis of novel nanomaterials; on the other hand, strong magnetic response could realize rapid separation and the outstanding hydrophilicity of polyethylene glycol makes Fe3O4@TiO2@PEG nanomaterials show superior performance for glycopeptides enrichment with ultralow limit of detection (0.1mol/μL) and high selectivity (1:100). 28712551 3 76 theme ultralow 1017:1024 arg1 limit 1026:1030 ultralow limit 1017:1030 ultralow limit of detection (0.1mol/μL) 1017:1055 On one hand, the special interaction of titanium-thiol makes the synthetic manipulation simple and provides a new idea for design and synthesis of novel nanomaterials; on the other hand, strong magnetic response could realize rapid separation and the outstanding hydrophilicity of polyethylene glycol makes Fe3O4@TiO2@PEG nanomaterials show superior performance for glycopeptides enrichment with ultralow limit of detection (0.1mol/μL) and high selectivity (1:100). 28712551 2 77 theme interaction 386:396 arg1 advantages 368:377 advantages 368:377 advantages of the interaction between titania and thiol groups 368:429 In this work, by taking advantages of the interaction between titania and thiol groups, thiol-polyethylene glycol functionalized magnetic titania nanomaterials (denoted as Fe3O4@TiO2@PEG) were firstly fabricated as an excellent hydrophilic adsorbent of N-linked glycopeptides. 28712551 1 78 theme capture 265:271 arg1 glycopeptides 273:285 capture glycopeptides 265:285 capture glycopeptides from complex biological samples for biomarker discovery 265:341 As protein N-glycosylation involved in generation and development of various cancers and diseases, it is vital to capture glycopeptides from complex biological samples for biomarker discovery. 28535302 0 0 theme cells 124:128 arg1 radiosensitivity 79:94 the cetuximab-induced radiosensitivity 57:94 the cetuximab-induced radiosensitivity of nasopharyngeal carcinoma cells 57:128 Inhibition of N-acetylglucosaminyltransferase V enhances the cetuximab-induced radiosensitivity of nasopharyngeal carcinoma cells likely through EGFR N-glycan alterations. 28535302 1 1 theme oligosaccharides 289:304 arg1 branching 276:284 the N-linked β-1-6 branching 257:284 the N-linked β-1-6 branching of oligosaccharides 257:304 N-acetylglucosaminyltransferase V (GnT-V), an enzyme that catalyzes the formation of the N-linked β-1-6 branching of oligosaccharides, is related to the radiosensitivity of nasopharyngeal carcinoma (NPC). 28535302 0 2 theme carcinoma 114:122 arg1 cells 124:128 nasopharyngeal carcinoma cells 99:128 nasopharyngeal carcinoma cells 99:128 Inhibition of N-acetylglucosaminyltransferase V enhances the cetuximab-induced radiosensitivity of nasopharyngeal carcinoma cells likely through EGFR N-glycan alterations. 28535302 2 3 from radiosensitizer 460:474 arg1 treatment 483:491 the treatment 479:491 the treatment of NPC 479:498 Cetuximab (C225) is an epidermal growth factor receptor (EGFR) inhibitor used as a radiosensitizer in the treatment of NPC. 28535302 4 4 from branching 772:780 arg1 EGFR 809:812 the EGFR 805:812 the EGFR 805:812 The results from two NPC cell lines (CNE1 and CNE2) revealed that the silencing of GnT-V enhanced cetuximab-induced radiosensitivity by decreasing the β-1-6 branching of oligosaccharides on the EGFR. 28535302 5 5 theme cell 911:914 arg1 viability 916:924 cell viability 911:924 cell viability 911:924 GnT-V down-regulation combined with cetuximab decreased the survival fraction, healing rate and cell viability and increased the apoptosis rate. 28535302 6 6 theme irradiation 1008:1018 arg1 combination 979:989 the combination 975:989 the combination of cetuximab and irradiation 975:1018 Concomitantly, the combination of cetuximab and irradiation did not change the EGFR mRNA and protein levels and decreased the β-1-6 branching on the EGFR. 28535302 7 7 theme PI3K/Akt 1199:1206 arg1 EGF 1177:1179 EGF 1177:1179 EGF 1177:1179 Subsequently, we further explored the signaling downstream of EGF, particularly the PI3K/Akt signaling pathway, and discovered that treatment consisting of GnT-V down-regulation, irradiation and cetuximab was negatively correlated with phospho-Akt and phspho-PI3K. 28535302 7 7 theme PI3K/Akt 1199:1206 arg1 pathway 1218:1224 the PI3K/Akt signaling pathway 1195:1224 the PI3K/Akt signaling pathway 1195:1224 Subsequently, we further explored the signaling downstream of EGF, particularly the PI3K/Akt signaling pathway, and discovered that treatment consisting of GnT-V down-regulation, irradiation and cetuximab was negatively correlated with phospho-Akt and phspho-PI3K. 28535302 9 8 theme NPC 1631:1633 arg1 radiosensitivity 1635:1650 NPC radiosensitivity 1631:1650 NPC radiosensitivity 1631:1650 In summary, our study demonstrated that the combination of decreased GnT-V activity and cetuximab enhanced NPC radiosensitivity, and the possible mechanism underlying this effect might involve the N-linked β1-6 branching of the EGFR. 28535302 5 9 theme apoptosis 944:952 arg1 rate 954:957 the apoptosis rate 940:957 the apoptosis rate 940:957 GnT-V down-regulation combined with cetuximab decreased the survival fraction, healing rate and cell viability and increased the apoptosis rate. 28535302 9 10 theme decreased 1583:1591 arg1 activity 1599:1606 decreased GnT-V activity 1583:1606 decreased GnT-V activity 1583:1606 In summary, our study demonstrated that the combination of decreased GnT-V activity and cetuximab enhanced NPC radiosensitivity, and the possible mechanism underlying this effect might involve the N-linked β1-6 branching of the EGFR. 28535302 3 11 theme molecular 535:543 arg1 GnT-V 524:528 GnT-V 524:528 GnT-V 524:528 In this study, we used GnT-V as a molecular target to further sensitize cetuximab-treated NPC cells to radiation. 28535302 3 11 theme molecular 535:543 arg1 target 545:550 a molecular target 533:550 a molecular target to further sensitize cetuximab-treated NPC cells to radiation 533:612 In this study, we used GnT-V as a molecular target to further sensitize cetuximab-treated NPC cells to radiation. 28535302 6 12 theme cetuximab 994:1002 arg1 combination 979:989 the combination 975:989 the combination of cetuximab and irradiation 975:1018 Concomitantly, the combination of cetuximab and irradiation did not change the EGFR mRNA and protein levels and decreased the β-1-6 branching on the EGFR. 28535302 0 13 theme N-glycan 150:157 arg1 alterations 159:169 EGFR N-glycan alterations 145:169 EGFR N-glycan alterations 145:169 Inhibition of N-acetylglucosaminyltransferase V enhances the cetuximab-induced radiosensitivity of nasopharyngeal carcinoma cells likely through EGFR N-glycan alterations. 28535302 9 14 theme N-linked 1721:1728 arg1 branching 1735:1743 the N-linked β1-6 branching 1717:1743 the N-linked β1-6 branching of the EGFR 1717:1755 In summary, our study demonstrated that the combination of decreased GnT-V activity and cetuximab enhanced NPC radiosensitivity, and the possible mechanism underlying this effect might involve the N-linked β1-6 branching of the EGFR. 28535302 9 15 theme GnT-V 1593:1597 arg1 activity 1599:1606 decreased GnT-V activity 1583:1606 decreased GnT-V activity 1583:1606 In summary, our study demonstrated that the combination of decreased GnT-V activity and cetuximab enhanced NPC radiosensitivity, and the possible mechanism underlying this effect might involve the N-linked β1-6 branching of the EGFR. 28535302 8 16 dep in 1392:1393 arg1 vivo 1395:1398 vivo 1395:1398 vivo 1395:1398 Finally, an in vivo experiment with radiotherapy revealed that the combination of GnT-V down-regulation and cetuximab decelerated tumor growth. 28535302 2 17 theme receptor 424:431 arg1 Cetuximab 377:385 Cetuximab 377:385 Cetuximab (C225) 377:392 Cetuximab (C225) is an epidermal growth factor receptor (EGFR) inhibitor used as a radiosensitizer in the treatment of NPC. 28535302 2 17 theme receptor 424:431 arg1 inhibitor 440:448 an epidermal growth factor receptor (EGFR) inhibitor 397:448 an epidermal growth factor receptor (EGFR) inhibitor used as a radiosensitizer in the treatment of NPC 397:498 Cetuximab (C225) is an epidermal growth factor receptor (EGFR) inhibitor used as a radiosensitizer in the treatment of NPC. 28535302 0 18 theme EGFR 145:148 arg1 alterations 159:169 EGFR N-glycan alterations 145:169 EGFR N-glycan alterations 145:169 Inhibition of N-acetylglucosaminyltransferase V enhances the cetuximab-induced radiosensitivity of nasopharyngeal carcinoma cells likely through EGFR N-glycan alterations. 28535302 8 19 with experiment 1400:1409 arg1 radiotherapy 1416:1427 radiotherapy 1416:1427 radiotherapy 1416:1427 Finally, an in vivo experiment with radiotherapy revealed that the combination of GnT-V down-regulation and cetuximab decelerated tumor growth. 28535302 4 20 theme β-1-6 766:770 arg1 branching 772:780 the β-1-6 branching 762:780 the β-1-6 branching of oligosaccharides on the EGFR 762:812 The results from two NPC cell lines (CNE1 and CNE2) revealed that the silencing of GnT-V enhanced cetuximab-induced radiosensitivity by decreasing the β-1-6 branching of oligosaccharides on the EGFR. 28535302 2 21 theme factor 417:422 arg1 EGFR 434:437 EGFR 434:437 EGFR 434:437 Cetuximab (C225) is an epidermal growth factor receptor (EGFR) inhibitor used as a radiosensitizer in the treatment of NPC. 28535302 2 21 theme factor 417:422 arg1 receptor 424:431 epidermal growth factor receptor 400:431 an epidermal growth factor receptor (EGFR) inhibitor used as a radiosensitizer in the treatment of NPC 397:498 Cetuximab (C225) is an epidermal growth factor receptor (EGFR) inhibitor used as a radiosensitizer in the treatment of NPC. 28535302 7 22 theme EGF 1177:1179 arg1 signaling 1153:1161 the signaling downstream 1149:1172 the signaling downstream of EGF, particularly the PI3K/Akt signaling pathway 1149:1224 Subsequently, we further explored the signaling downstream of EGF, particularly the PI3K/Akt signaling pathway, and discovered that treatment consisting of GnT-V down-regulation, irradiation and cetuximab was negatively correlated with phospho-Akt and phspho-PI3K. 28535302 2 23 theme NPC 496:498 arg1 treatment 483:491 the treatment 479:491 the treatment of NPC 479:498 Cetuximab (C225) is an epidermal growth factor receptor (EGFR) inhibitor used as a radiosensitizer in the treatment of NPC. 28535302 4 24 theme cetuximab-induced 713:729 arg1 radiosensitivity 731:746 cetuximab-induced radiosensitivity 713:746 cetuximab-induced radiosensitivity 713:746 The results from two NPC cell lines (CNE1 and CNE2) revealed that the silencing of GnT-V enhanced cetuximab-induced radiosensitivity by decreasing the β-1-6 branching of oligosaccharides on the EGFR. 28535302 4 25 from lines 645:649 arg1 results 619:625 The results 615:625 The results from two NPC cell lines (CNE1 and CNE2) 615:665 The results from two NPC cell lines (CNE1 and CNE2) revealed that the silencing of GnT-V enhanced cetuximab-induced radiosensitivity by decreasing the β-1-6 branching of oligosaccharides on the EGFR. 28535302 2 26 theme growth 410:415 arg1 EGFR 434:437 EGFR 434:437 EGFR 434:437 Cetuximab (C225) is an epidermal growth factor receptor (EGFR) inhibitor used as a radiosensitizer in the treatment of NPC. 28535302 2 26 theme growth 410:415 arg1 receptor 424:431 epidermal growth factor receptor 400:431 an epidermal growth factor receptor (EGFR) inhibitor used as a radiosensitizer in the treatment of NPC 397:498 Cetuximab (C225) is an epidermal growth factor receptor (EGFR) inhibitor used as a radiosensitizer in the treatment of NPC. 28535302 1 27 link N-linked 261:268 arg1 branching 276:284 the N-linked β-1-6 branching 257:284 the N-linked β-1-6 branching of oligosaccharides 257:304 N-acetylglucosaminyltransferase V (GnT-V), an enzyme that catalyzes the formation of the N-linked β-1-6 branching of oligosaccharides, is related to the radiosensitivity of nasopharyngeal carcinoma (NPC). 28535302 9 28 theme cetuximab 1612:1620 arg1 combination 1568:1578 the combination 1564:1578 the combination of decreased GnT-V activity and cetuximab 1564:1620 In summary, our study demonstrated that the combination of decreased GnT-V activity and cetuximab enhanced NPC radiosensitivity, and the possible mechanism underlying this effect might involve the N-linked β1-6 branching of the EGFR. 28535302 2 29 theme epidermal 400:408 arg1 EGFR 434:437 EGFR 434:437 EGFR 434:437 Cetuximab (C225) is an epidermal growth factor receptor (EGFR) inhibitor used as a radiosensitizer in the treatment of NPC. 28535302 2 29 theme epidermal 400:408 arg1 receptor 424:431 epidermal growth factor receptor 400:431 an epidermal growth factor receptor (EGFR) inhibitor used as a radiosensitizer in the treatment of NPC 397:498 Cetuximab (C225) is an epidermal growth factor receptor (EGFR) inhibitor used as a radiosensitizer in the treatment of NPC. 28535302 0 30 theme V 46:46 arg1 Inhibition 0:9 Inhibition 0:9 Inhibition of N-acetylglucosaminyltransferase V 0:46 Inhibition of N-acetylglucosaminyltransferase V enhances the cetuximab-induced radiosensitivity of nasopharyngeal carcinoma cells likely through EGFR N-glycan alterations. 28535302 8 31 theme GnT-V 1462:1466 arg1 combination 1447:1457 the combination 1443:1457 the combination of GnT-V down-regulation and cetuximab 1443:1496 Finally, an in vivo experiment with radiotherapy revealed that the combination of GnT-V down-regulation and cetuximab decelerated tumor growth. 28535302 9 32 theme possible 1661:1668 arg1 mechanism 1670:1678 the possible mechanism 1657:1678 the possible mechanism underlying this effect 1657:1701 In summary, our study demonstrated that the combination of decreased GnT-V activity and cetuximab enhanced NPC radiosensitivity, and the possible mechanism underlying this effect might involve the N-linked β1-6 branching of the EGFR. 28535302 0 33 theme N-acetylglucosaminyltransferase 14:44 arg1 V 46:46 N-acetylglucosaminyltransferase V 14:46 N-acetylglucosaminyltransferase V 14:46 Inhibition of N-acetylglucosaminyltransferase V enhances the cetuximab-induced radiosensitivity of nasopharyngeal carcinoma cells likely through EGFR N-glycan alterations. 28535302 9 34 theme EGFR 1752:1755 arg1 branching 1735:1743 the N-linked β1-6 branching 1717:1743 the N-linked β1-6 branching of the EGFR 1717:1755 In summary, our study demonstrated that the combination of decreased GnT-V activity and cetuximab enhanced NPC radiosensitivity, and the possible mechanism underlying this effect might involve the N-linked β1-6 branching of the EGFR. 28535302 9 35 link N-linked 1721:1728 arg1 branching 1735:1743 the N-linked β1-6 branching 1717:1743 the N-linked β1-6 branching of the EGFR 1717:1755 In summary, our study demonstrated that the combination of decreased GnT-V activity and cetuximab enhanced NPC radiosensitivity, and the possible mechanism underlying this effect might involve the N-linked β1-6 branching of the EGFR. 28535302 6 36 theme protein 1053:1059 arg1 levels 1061:1066 the EGFR mRNA and protein levels 1035:1066 the EGFR mRNA and protein levels 1035:1066 Concomitantly, the combination of cetuximab and irradiation did not change the EGFR mRNA and protein levels and decreased the β-1-6 branching on the EGFR. 28535302 4 37 theme cell 640:643 arg1 CNE2 661:664 CNE2 661:664 CNE2 661:664 The results from two NPC cell lines (CNE1 and CNE2) revealed that the silencing of GnT-V enhanced cetuximab-induced radiosensitivity by decreasing the β-1-6 branching of oligosaccharides on the EGFR. 28535302 4 37 theme cell 640:643 arg1 CNE1 652:655 CNE1 652:655 CNE1 652:655 The results from two NPC cell lines (CNE1 and CNE2) revealed that the silencing of GnT-V enhanced cetuximab-induced radiosensitivity by decreasing the β-1-6 branching of oligosaccharides on the EGFR. 28535302 4 37 theme cell 640:643 arg1 lines 645:649 two NPC cell lines 632:649 two NPC cell lines (CNE1 and CNE2) 632:665 The results from two NPC cell lines (CNE1 and CNE2) revealed that the silencing of GnT-V enhanced cetuximab-induced radiosensitivity by decreasing the β-1-6 branching of oligosaccharides on the EGFR. 28535302 6 38 theme β-1-6 1086:1090 arg1 branching 1092:1100 the β-1-6 branching 1082:1100 the β-1-6 branching on the EGFR 1082:1112 Concomitantly, the combination of cetuximab and irradiation did not change the EGFR mRNA and protein levels and decreased the β-1-6 branching on the EGFR. 28535302 1 39 theme nasopharyngeal 345:358 arg1 carcinoma 360:368 nasopharyngeal carcinoma 345:368 nasopharyngeal carcinoma (NPC) 345:374 N-acetylglucosaminyltransferase V (GnT-V), an enzyme that catalyzes the formation of the N-linked β-1-6 branching of oligosaccharides, is related to the radiosensitivity of nasopharyngeal carcinoma (NPC). 28535302 1 39 theme nasopharyngeal 345:358 arg1 NPC 371:373 NPC 371:373 NPC 371:373 N-acetylglucosaminyltransferase V (GnT-V), an enzyme that catalyzes the formation of the N-linked β-1-6 branching of oligosaccharides, is related to the radiosensitivity of nasopharyngeal carcinoma (NPC). 28535302 5 40 theme GnT-V 815:819 arg1 down-regulation 821:835 GnT-V down-regulation 815:835 GnT-V down-regulation combined with cetuximab 815:859 GnT-V down-regulation combined with cetuximab decreased the survival fraction, healing rate and cell viability and increased the apoptosis rate. 28535302 4 41 theme NPC 636:638 arg1 CNE2 661:664 CNE2 661:664 CNE2 661:664 The results from two NPC cell lines (CNE1 and CNE2) revealed that the silencing of GnT-V enhanced cetuximab-induced radiosensitivity by decreasing the β-1-6 branching of oligosaccharides on the EGFR. 28535302 4 41 theme NPC 636:638 arg1 CNE1 652:655 CNE1 652:655 CNE1 652:655 The results from two NPC cell lines (CNE1 and CNE2) revealed that the silencing of GnT-V enhanced cetuximab-induced radiosensitivity by decreasing the β-1-6 branching of oligosaccharides on the EGFR. 28535302 4 41 theme NPC 636:638 arg1 lines 645:649 two NPC cell lines 632:649 two NPC cell lines (CNE1 and CNE2) 632:665 The results from two NPC cell lines (CNE1 and CNE2) revealed that the silencing of GnT-V enhanced cetuximab-induced radiosensitivity by decreasing the β-1-6 branching of oligosaccharides on the EGFR. 28535302 1 42 theme carcinoma 360:368 arg1 radiosensitivity 325:340 the radiosensitivity 321:340 the radiosensitivity of nasopharyngeal carcinoma (NPC) 321:374 N-acetylglucosaminyltransferase V (GnT-V), an enzyme that catalyzes the formation of the N-linked β-1-6 branching of oligosaccharides, is related to the radiosensitivity of nasopharyngeal carcinoma (NPC). 28535302 8 43 theme in 1392:1393 arg1 experiment 1400:1409 an in vivo experiment 1389:1409 an in vivo experiment with radiotherapy 1389:1427 Finally, an in vivo experiment with radiotherapy revealed that the combination of GnT-V down-regulation and cetuximab decelerated tumor growth. 28535302 8 44 theme cetuximab 1488:1496 arg1 combination 1447:1457 the combination 1443:1457 the combination of GnT-V down-regulation and cetuximab 1443:1496 Finally, an in vivo experiment with radiotherapy revealed that the combination of GnT-V down-regulation and cetuximab decelerated tumor growth. 28535302 3 45 theme cetuximab-treated 573:589 arg1 cells 595:599 cetuximab-treated NPC cells 573:599 cetuximab-treated NPC cells 573:599 In this study, we used GnT-V as a molecular target to further sensitize cetuximab-treated NPC cells to radiation. 28535302 8 46 dep GnT-V 1462:1466 arg1 down-regulation 1468:1482 down-regulation 1468:1482 down-regulation 1468:1482 Finally, an in vivo experiment with radiotherapy revealed that the combination of GnT-V down-regulation and cetuximab decelerated tumor growth. 28535302 0 47 theme cetuximab-induced 61:77 arg1 radiosensitivity 79:94 the cetuximab-induced radiosensitivity 57:94 the cetuximab-induced radiosensitivity of nasopharyngeal carcinoma cells 57:128 Inhibition of N-acetylglucosaminyltransferase V enhances the cetuximab-induced radiosensitivity of nasopharyngeal carcinoma cells likely through EGFR N-glycan alterations. 28535302 9 48 theme β1-6 1730:1733 arg1 branching 1735:1743 the N-linked β1-6 branching 1717:1743 the N-linked β1-6 branching of the EGFR 1717:1755 In summary, our study demonstrated that the combination of decreased GnT-V activity and cetuximab enhanced NPC radiosensitivity, and the possible mechanism underlying this effect might involve the N-linked β1-6 branching of the EGFR. 28535302 3 49 theme NPC 591:593 arg1 cells 595:599 cetuximab-treated NPC cells 573:599 cetuximab-treated NPC cells 573:599 In this study, we used GnT-V as a molecular target to further sensitize cetuximab-treated NPC cells to radiation. 28535302 4 50 theme GnT-V 698:702 arg1 silencing 685:693 the silencing 681:693 the silencing of GnT-V 681:702 The results from two NPC cell lines (CNE1 and CNE2) revealed that the silencing of GnT-V enhanced cetuximab-induced radiosensitivity by decreasing the β-1-6 branching of oligosaccharides on the EGFR. 28535302 7 51 theme downstream 1163:1172 arg1 signaling 1153:1161 the signaling downstream 1149:1172 the signaling downstream of EGF, particularly the PI3K/Akt signaling pathway 1149:1224 Subsequently, we further explored the signaling downstream of EGF, particularly the PI3K/Akt signaling pathway, and discovered that treatment consisting of GnT-V down-regulation, irradiation and cetuximab was negatively correlated with phospho-Akt and phspho-PI3K. 28535302 8 52 theme tumor 1510:1514 arg1 growth 1516:1521 tumor growth 1510:1521 tumor growth 1510:1521 Finally, an in vivo experiment with radiotherapy revealed that the combination of GnT-V down-regulation and cetuximab decelerated tumor growth. 28535302 4 53 theme oligosaccharides 785:800 arg1 branching 772:780 the β-1-6 branching 762:780 the β-1-6 branching of oligosaccharides on the EGFR 762:812 The results from two NPC cell lines (CNE1 and CNE2) revealed that the silencing of GnT-V enhanced cetuximab-induced radiosensitivity by decreasing the β-1-6 branching of oligosaccharides on the EGFR. 28535302 1 54 theme N-acetylglucosaminyltransferase 172:202 arg1 GnT-V 207:211 GnT-V 207:211 GnT-V 207:211 N-acetylglucosaminyltransferase V (GnT-V), an enzyme that catalyzes the formation of the N-linked β-1-6 branching of oligosaccharides, is related to the radiosensitivity of nasopharyngeal carcinoma (NPC). 28535302 1 54 theme N-acetylglucosaminyltransferase 172:202 arg1 V 204:204 N-acetylglucosaminyltransferase V 172:204 N-acetylglucosaminyltransferase V (GnT-V) 172:212 N-acetylglucosaminyltransferase V (GnT-V), an enzyme that catalyzes the formation of the N-linked β-1-6 branching of oligosaccharides, is related to the radiosensitivity of nasopharyngeal carcinoma (NPC). 28535302 1 54 theme N-acetylglucosaminyltransferase 172:202 arg1 enzyme 218:223 an enzyme 215:223 an enzyme that catalyzes the formation of the N-linked β-1-6 branching of oligosaccharides 215:304 N-acetylglucosaminyltransferase V (GnT-V), an enzyme that catalyzes the formation of the N-linked β-1-6 branching of oligosaccharides, is related to the radiosensitivity of nasopharyngeal carcinoma (NPC). 28535302 1 55 theme N-linked 261:268 arg1 branching 276:284 the N-linked β-1-6 branching 257:284 the N-linked β-1-6 branching of oligosaccharides 257:304 N-acetylglucosaminyltransferase V (GnT-V), an enzyme that catalyzes the formation of the N-linked β-1-6 branching of oligosaccharides, is related to the radiosensitivity of nasopharyngeal carcinoma (NPC). 28535302 9 56 theme activity 1599:1606 arg1 combination 1568:1578 the combination 1564:1578 the combination of decreased GnT-V activity and cetuximab 1564:1620 In summary, our study demonstrated that the combination of decreased GnT-V activity and cetuximab enhanced NPC radiosensitivity, and the possible mechanism underlying this effect might involve the N-linked β1-6 branching of the EGFR. 28535302 1 57 theme β-1-6 270:274 arg1 branching 276:284 the N-linked β-1-6 branching 257:284 the N-linked β-1-6 branching of oligosaccharides 257:304 N-acetylglucosaminyltransferase V (GnT-V), an enzyme that catalyzes the formation of the N-linked β-1-6 branching of oligosaccharides, is related to the radiosensitivity of nasopharyngeal carcinoma (NPC). 28535302 0 58 theme nasopharyngeal 99:112 arg1 cells 124:128 nasopharyngeal carcinoma cells 99:128 nasopharyngeal carcinoma cells 99:128 Inhibition of N-acetylglucosaminyltransferase V enhances the cetuximab-induced radiosensitivity of nasopharyngeal carcinoma cells likely through EGFR N-glycan alterations. 28535302 6 59 theme mRNA 1044:1047 arg1 levels 1061:1066 the EGFR mRNA and protein levels 1035:1066 the EGFR mRNA and protein levels 1035:1066 Concomitantly, the combination of cetuximab and irradiation did not change the EGFR mRNA and protein levels and decreased the β-1-6 branching on the EGFR. 28535302 3 60 used used 519:522 arg2 we 516:517 we 516:517 we 516:517 In this study, we used GnT-V as a molecular target to further sensitize cetuximab-treated NPC cells to radiation. 28535302 6 61 from branching 1092:1100 arg1 EGFR 1109:1112 the EGFR 1105:1112 the EGFR 1105:1112 Concomitantly, the combination of cetuximab and irradiation did not change the EGFR mRNA and protein levels and decreased the β-1-6 branching on the EGFR. 28535302 5 62 theme healing 894:900 arg1 rate 902:905 healing rate 894:905 healing rate 894:905 GnT-V down-regulation combined with cetuximab decreased the survival fraction, healing rate and cell viability and increased the apoptosis rate. 28535302 5 63 theme survival 875:882 arg1 fraction 884:891 the survival fraction 871:891 the survival fraction 871:891 GnT-V down-regulation combined with cetuximab decreased the survival fraction, healing rate and cell viability and increased the apoptosis rate. 28535302 1 64 theme branching 276:284 arg1 formation 244:252 the formation 240:252 the formation of the N-linked β-1-6 branching of oligosaccharides 240:304 N-acetylglucosaminyltransferase V (GnT-V), an enzyme that catalyzes the formation of the N-linked β-1-6 branching of oligosaccharides, is related to the radiosensitivity of nasopharyngeal carcinoma (NPC). 28535302 4 65 dep lines 645:649 arg1 CNE2 661:664 CNE2 661:664 CNE2 661:664 The results from two NPC cell lines (CNE1 and CNE2) revealed that the silencing of GnT-V enhanced cetuximab-induced radiosensitivity by decreasing the β-1-6 branching of oligosaccharides on the EGFR. 28535302 4 65 dep lines 645:649 arg1 CNE1 652:655 CNE1 652:655 CNE1 652:655 The results from two NPC cell lines (CNE1 and CNE2) revealed that the silencing of GnT-V enhanced cetuximab-induced radiosensitivity by decreasing the β-1-6 branching of oligosaccharides on the EGFR. 28535302 4 65 dep lines 645:649 arg1 lines 645:649 two NPC cell lines 632:649 two NPC cell lines (CNE1 and CNE2) 632:665 The results from two NPC cell lines (CNE1 and CNE2) revealed that the silencing of GnT-V enhanced cetuximab-induced radiosensitivity by decreasing the β-1-6 branching of oligosaccharides on the EGFR. 28535302 7 66 theme GnT-V 1271:1275 arg1 down-regulation 1277:1291 GnT-V down-regulation 1271:1291 GnT-V down-regulation 1271:1291 Subsequently, we further explored the signaling downstream of EGF, particularly the PI3K/Akt signaling pathway, and discovered that treatment consisting of GnT-V down-regulation, irradiation and cetuximab was negatively correlated with phospho-Akt and phspho-PI3K. 28535302 6 67 theme EGFR 1039:1042 arg1 mRNA 1044:1047 EGFR mRNA 1039:1047 EGFR mRNA 1039:1047 Concomitantly, the combination of cetuximab and irradiation did not change the EGFR mRNA and protein levels and decreased the β-1-6 branching on the EGFR. 28535302 7 68 theme signaling 1208:1216 arg1 EGF 1177:1179 EGF 1177:1179 EGF 1177:1179 Subsequently, we further explored the signaling downstream of EGF, particularly the PI3K/Akt signaling pathway, and discovered that treatment consisting of GnT-V down-regulation, irradiation and cetuximab was negatively correlated with phospho-Akt and phspho-PI3K. 28535302 7 68 theme signaling 1208:1216 arg1 pathway 1218:1224 the PI3K/Akt signaling pathway 1195:1224 the PI3K/Akt signaling pathway 1195:1224 Subsequently, we further explored the signaling downstream of EGF, particularly the PI3K/Akt signaling pathway, and discovered that treatment consisting of GnT-V down-regulation, irradiation and cetuximab was negatively correlated with phospho-Akt and phspho-PI3K. 28334446 4 0 theme CE-LIF 640:645 arg1 glycoprofiling 647:660 CE-LIF glycoprofiling 640:660 CE-LIF glycoprofiling of the FFPE mouse tissues 640:686 After CE-LIF glycoprofiling of the FFPE mouse tissues, the N-glycan pool of the lung specimen was subject to further investigation by exoglycosidase array based carbohydrate sequencing. 28334446 5 1 dep the 886:888 arg1 help 890:893 help 890:893 help 890:893 Structural assignment of the oligosaccharides was accomplished by the help of the GUcal software and the associated database, based on the mobility shifts after treatments with the corresponding exoglycosidase reaction mixtures. 28334446 6 2 theme sialylated 1244:1253 arg1 9 1267:1267 9 1267:1267 9 1267:1267 Sixteen major N-linked carbohydrate structures were sequenced from the mouse lung FFPE tissue glycome and identified, as high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides. 28334446 6 2 theme sialylated 1244:1253 arg1 bianennary 1255:1264 sialylated bianennary 1244:1264 sialylated bianennary (9) 1244:1268 Sixteen major N-linked carbohydrate structures were sequenced from the mouse lung FFPE tissue glycome and identified, as high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides. 28334446 0 3 dep formalin-fixed 84:97 arg1 paraffin-embedded 99:115 paraffin-embedded 99:115 paraffin-embedded 99:115 Molecular glycopathology by capillary electrophoresis: Analysis of the N-glycome of formalin-fixed paraffin-embedded mouse tissue samples. 28334446 1 4 from samples 353:359 arg1 N-glycans 285:293 endoglycosidase released and fluorophore-labeled N-glycans 236:293 endoglycosidase released and fluorophore-labeled N-glycans from formalin-fixed paraffin-embedded (FFPE) mouse tissue samples of lung, brain, heart, spleen, liver, kidney and intestine 236:418 Capillary electrophoresis with laser-induced fluorescence (CE-LIF) detection was used to analyze endoglycosidase released and fluorophore-labeled N-glycans from formalin-fixed paraffin-embedded (FFPE) mouse tissue samples of lung, brain, heart, spleen, liver, kidney and intestine. 28334446 4 5 theme specimen 719:726 arg1 pool 702:705 the N-glycan pool 689:705 the N-glycan pool of the lung specimen 689:726 After CE-LIF glycoprofiling of the FFPE mouse tissues, the N-glycan pool of the lung specimen was subject to further investigation by exoglycosidase array based carbohydrate sequencing. 28334446 4 5 theme specimen 719:726 arg1 subject 732:738 subject 732:738 subject 732:738 After CE-LIF glycoprofiling of the FFPE mouse tissues, the N-glycan pool of the lung specimen was subject to further investigation by exoglycosidase array based carbohydrate sequencing. 28334446 6 6 theme major 1057:1061 arg1 structures 1085:1094 Sixteen major N-linked carbohydrate structures 1049:1094 Sixteen major N-linked carbohydrate structures 1049:1094 Sixteen major N-linked carbohydrate structures were sequenced from the mouse lung FFPE tissue glycome and identified, as high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides. 28334446 6 6 theme major 1057:1061 arg1 oligosaccharides 1270:1285 high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides 1170:1285 high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides 1170:1285 Sixteen major N-linked carbohydrate structures were sequenced from the mouse lung FFPE tissue glycome and identified, as high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides. 28334446 6 7 theme sialylated 1211:1220 arg1 structures 1085:1094 Sixteen major N-linked carbohydrate structures 1049:1094 Sixteen major N-linked carbohydrate structures 1049:1094 Sixteen major N-linked carbohydrate structures were sequenced from the mouse lung FFPE tissue glycome and identified, as high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides. 28334446 6 7 theme sialylated 1211:1220 arg1 oligosaccharides 1270:1285 high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides 1170:1285 high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides 1170:1285 Sixteen major N-linked carbohydrate structures were sequenced from the mouse lung FFPE tissue glycome and identified, as high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides. 28334446 6 8 gly sialylated 1211:1220 arg1 structures 1085:1094 Sixteen major N-linked carbohydrate structures 1049:1094 Sixteen major N-linked carbohydrate structures 1049:1094 Sixteen major N-linked carbohydrate structures were sequenced from the mouse lung FFPE tissue glycome and identified, as high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides. 28334446 6 8 gly sialylated 1211:1220 arg1 oligosaccharides 1270:1285 high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides 1170:1285 high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides 1170:1285 Sixteen major N-linked carbohydrate structures were sequenced from the mouse lung FFPE tissue glycome and identified, as high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides. 28334446 3 9 theme aminopyrene 608:618 arg1 trisulfonate 620:631 aminopyrene trisulfonate 608:631 aminopyrene trisulfonate 608:631 PNGase F mediated release of the N-linked oligosaccharides was followed by labeling with aminopyrene trisulfonate. 28334446 3 10 link N-linked 552:559 arg1 oligosaccharides 561:576 the N-linked oligosaccharides 548:576 the N-linked oligosaccharides 548:576 PNGase F mediated release of the N-linked oligosaccharides was followed by labeling with aminopyrene trisulfonate. 28334446 6 11 gly sialylated 1244:1253 arg1 9 1267:1267 9 1267:1267 9 1267:1267 Sixteen major N-linked carbohydrate structures were sequenced from the mouse lung FFPE tissue glycome and identified, as high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides. 28334446 6 11 gly sialylated 1244:1253 arg1 bianennary 1255:1264 sialylated bianennary 1244:1264 sialylated bianennary (9) 1244:1268 Sixteen major N-linked carbohydrate structures were sequenced from the mouse lung FFPE tissue glycome and identified, as high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides. 28334446 1 12 theme released 252:259 arg1 N-glycans 285:293 endoglycosidase released and fluorophore-labeled N-glycans 236:293 endoglycosidase released and fluorophore-labeled N-glycans from formalin-fixed paraffin-embedded (FFPE) mouse tissue samples of lung, brain, heart, spleen, liver, kidney and intestine 236:418 Capillary electrophoresis with laser-induced fluorescence (CE-LIF) detection was used to analyze endoglycosidase released and fluorophore-labeled N-glycans from formalin-fixed paraffin-embedded (FFPE) mouse tissue samples of lung, brain, heart, spleen, liver, kidney and intestine. 28334446 1 13 theme Capillary 139:147 arg1 electrophoresis 149:163 Capillary electrophoresis 139:163 Capillary electrophoresis with laser-induced fluorescence (CE-LIF) detection 139:214 Capillary electrophoresis with laser-induced fluorescence (CE-LIF) detection was used to analyze endoglycosidase released and fluorophore-labeled N-glycans from formalin-fixed paraffin-embedded (FFPE) mouse tissue samples of lung, brain, heart, spleen, liver, kidney and intestine. 28334446 1 14 used used 220:223 arg2 electrophoresis 149:163 Capillary electrophoresis 139:163 Capillary electrophoresis with laser-induced fluorescence (CE-LIF) detection 139:214 Capillary electrophoresis with laser-induced fluorescence (CE-LIF) detection was used to analyze endoglycosidase released and fluorophore-labeled N-glycans from formalin-fixed paraffin-embedded (FFPE) mouse tissue samples of lung, brain, heart, spleen, liver, kidney and intestine. 28334446 4 15 theme array 783:787 arg1 sequencing 808:817 exoglycosidase array based carbohydrate sequencing 768:817 exoglycosidase array based carbohydrate sequencing 768:817 After CE-LIF glycoprofiling of the FFPE mouse tissues, the N-glycan pool of the lung specimen was subject to further investigation by exoglycosidase array based carbohydrate sequencing. 28334446 6 16 theme mouse 1120:1124 arg1 glycome 1143:1149 the mouse lung FFPE tissue glycome 1116:1149 the mouse lung FFPE tissue glycome 1116:1149 Sixteen major N-linked carbohydrate structures were sequenced from the mouse lung FFPE tissue glycome and identified, as high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides. 28334446 1 17 dep paraffin-embedded 315:331 arg1 FFPE 334:337 FFPE 334:337 FFPE 334:337 Capillary electrophoresis with laser-induced fluorescence (CE-LIF) detection was used to analyze endoglycosidase released and fluorophore-labeled N-glycans from formalin-fixed paraffin-embedded (FFPE) mouse tissue samples of lung, brain, heart, spleen, liver, kidney and intestine. 28334446 1 18 theme fluorescence 184:195 arg1 detection 206:214 laser-induced fluorescence (CE-LIF) detection 170:214 laser-induced fluorescence (CE-LIF) detection 170:214 Capillary electrophoresis with laser-induced fluorescence (CE-LIF) detection was used to analyze endoglycosidase released and fluorophore-labeled N-glycans from formalin-fixed paraffin-embedded (FFPE) mouse tissue samples of lung, brain, heart, spleen, liver, kidney and intestine. 28334446 1 18 theme fluorescence 184:195 arg1 CE-LIF 198:203 CE-LIF 198:203 CE-LIF 198:203 Capillary electrophoresis with laser-induced fluorescence (CE-LIF) detection was used to analyze endoglycosidase released and fluorophore-labeled N-glycans from formalin-fixed paraffin-embedded (FFPE) mouse tissue samples of lung, brain, heart, spleen, liver, kidney and intestine. 28334446 4 19 theme further 743:749 arg1 investigation 751:763 further investigation 743:763 further investigation by exoglycosidase array based carbohydrate sequencing 743:817 After CE-LIF glycoprofiling of the FFPE mouse tissues, the N-glycan pool of the lung specimen was subject to further investigation by exoglycosidase array based carbohydrate sequencing. 28334446 7 20 theme latter 1301:1306 arg1 ones 1308:1311 these latter ones 1295:1311 these latter ones 1295:1311 Two of these latter ones also possessed alpha(1-3) linked galactose residues. 28334446 6 21 theme carbohydrate 1072:1083 arg1 structures 1085:1094 Sixteen major N-linked carbohydrate structures 1049:1094 Sixteen major N-linked carbohydrate structures 1049:1094 Sixteen major N-linked carbohydrate structures were sequenced from the mouse lung FFPE tissue glycome and identified, as high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides. 28334446 6 21 theme carbohydrate 1072:1083 arg1 oligosaccharides 1270:1285 high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides 1170:1285 high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides 1170:1285 Sixteen major N-linked carbohydrate structures were sequenced from the mouse lung FFPE tissue glycome and identified, as high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides. 28334446 0 22 theme tissue 123:128 arg1 samples 130:136 formalin-fixed paraffin-embedded mouse tissue samples 84:136 formalin-fixed paraffin-embedded mouse tissue samples 84:136 Molecular glycopathology by capillary electrophoresis: Analysis of the N-glycome of formalin-fixed paraffin-embedded mouse tissue samples. 28334446 2 23 dep deparaffinized 449:462 arg1 samples 430:436 The FFPE samples 421:436 The FFPE samples 421:436 The FFPE samples were first deparaffinized followed by solubilization and glycoprotein retrieval. 28334446 2 23 dep deparaffinized 449:462 arg1 deparaffinized 449:462 deparaffinized 449:462 deparaffinized 449:462 The FFPE samples were first deparaffinized followed by solubilization and glycoprotein retrieval. 28334446 2 23 dep deparaffinized 449:462 arg1 followed 464:471 followed 464:471 followed by solubilization and glycoprotein retrieval 464:516 The FFPE samples were first deparaffinized followed by solubilization and glycoprotein retrieval. 28334446 0 24 theme N-glycome 71:79 arg1 Analysis 55:62 Analysis 55:62 Molecular glycopathology by capillary electrophoresis: Analysis of the N-glycome of formalin-fixed paraffin-embedded mouse tissue samples. 0:137 Molecular glycopathology by capillary electrophoresis: Analysis of the N-glycome of formalin-fixed paraffin-embedded mouse tissue samples. 28334446 4 25 theme carbohydrate 795:806 arg1 sequencing 808:817 exoglycosidase array based carbohydrate sequencing 768:817 exoglycosidase array based carbohydrate sequencing 768:817 After CE-LIF glycoprofiling of the FFPE mouse tissues, the N-glycan pool of the lung specimen was subject to further investigation by exoglycosidase array based carbohydrate sequencing. 28334446 0 26 theme Molecular 0:8 arg1 glycopathology 10:23 Molecular glycopathology 0:23 Molecular glycopathology by capillary electrophoresis: Analysis of the N-glycome of formalin-fixed paraffin-embedded mouse tissue samples. 0:137 Molecular glycopathology by capillary electrophoresis: Analysis of the N-glycome of formalin-fixed paraffin-embedded mouse tissue samples. 28334446 5 27 theme exoglycosidase 1015:1028 arg1 mixtures 1039:1046 the corresponding exoglycosidase reaction mixtures 997:1046 the corresponding exoglycosidase reaction mixtures 997:1046 Structural assignment of the oligosaccharides was accomplished by the help of the GUcal software and the associated database, based on the mobility shifts after treatments with the corresponding exoglycosidase reaction mixtures. 28334446 1 28 theme tissue 346:351 arg1 samples 353:359 formalin-fixed paraffin-embedded (FFPE) mouse tissue samples 300:359 formalin-fixed paraffin-embedded (FFPE) mouse tissue samples of lung, brain, heart, spleen, liver, kidney and intestine 300:418 Capillary electrophoresis with laser-induced fluorescence (CE-LIF) detection was used to analyze endoglycosidase released and fluorophore-labeled N-glycans from formalin-fixed paraffin-embedded (FFPE) mouse tissue samples of lung, brain, heart, spleen, liver, kidney and intestine. 28334446 6 29 theme FFPE 1131:1134 arg1 glycome 1143:1149 the mouse lung FFPE tissue glycome 1116:1149 the mouse lung FFPE tissue glycome 1116:1149 Sixteen major N-linked carbohydrate structures were sequenced from the mouse lung FFPE tissue glycome and identified, as high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides. 28334446 2 30 theme glycoprotein 495:506 arg1 retrieval 508:516 glycoprotein retrieval 495:516 glycoprotein retrieval 495:516 The FFPE samples were first deparaffinized followed by solubilization and glycoprotein retrieval. 28334446 3 31 theme mediated 528:535 arg1 release 537:543 PNGase F mediated release 519:543 PNGase F mediated release of the N-linked oligosaccharides 519:576 PNGase F mediated release of the N-linked oligosaccharides was followed by labeling with aminopyrene trisulfonate. 28334446 3 32 with labeling 594:601 arg1 trisulfonate 620:631 aminopyrene trisulfonate 608:631 aminopyrene trisulfonate 608:631 PNGase F mediated release of the N-linked oligosaccharides was followed by labeling with aminopyrene trisulfonate. 28334446 2 33 gly glycoprotein 495:506 arg1 glycoprotein 495:506 glycoprotein retrieval 495:516 glycoprotein retrieval 495:516 The FFPE samples were first deparaffinized followed by solubilization and glycoprotein retrieval. 28334446 3 34 theme PNGase 519:524 arg1 F 526:526 PNGase F 519:526 PNGase F mediated release of the N-linked oligosaccharides 519:576 PNGase F mediated release of the N-linked oligosaccharides was followed by labeling with aminopyrene trisulfonate. 28334446 6 35 theme neutral 1187:1193 arg1 structures 1085:1094 Sixteen major N-linked carbohydrate structures 1049:1094 Sixteen major N-linked carbohydrate structures 1049:1094 Sixteen major N-linked carbohydrate structures were sequenced from the mouse lung FFPE tissue glycome and identified, as high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides. 28334446 6 35 theme neutral 1187:1193 arg1 oligosaccharides 1270:1285 high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides 1170:1285 high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides 1170:1285 Sixteen major N-linked carbohydrate structures were sequenced from the mouse lung FFPE tissue glycome and identified, as high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides. 28334446 7 36 theme linked 1339:1344 arg1 residues 1356:1363 alpha(1-3) linked galactose residues 1328:1363 alpha(1-3) linked galactose residues 1328:1363 Two of these latter ones also possessed alpha(1-3) linked galactose residues. 28334446 3 37 theme N-linked 552:559 arg1 oligosaccharides 561:576 the N-linked oligosaccharides 548:576 the N-linked oligosaccharides 548:576 PNGase F mediated release of the N-linked oligosaccharides was followed by labeling with aminopyrene trisulfonate. 28334446 4 38 theme mouse 674:678 arg1 tissues 680:686 the FFPE mouse tissues 665:686 the FFPE mouse tissues 665:686 After CE-LIF glycoprofiling of the FFPE mouse tissues, the N-glycan pool of the lung specimen was subject to further investigation by exoglycosidase array based carbohydrate sequencing. 28334446 1 39 theme formalin-fixed 300:313 arg1 samples 353:359 formalin-fixed paraffin-embedded (FFPE) mouse tissue samples 300:359 formalin-fixed paraffin-embedded (FFPE) mouse tissue samples of lung, brain, heart, spleen, liver, kidney and intestine 300:418 Capillary electrophoresis with laser-induced fluorescence (CE-LIF) detection was used to analyze endoglycosidase released and fluorophore-labeled N-glycans from formalin-fixed paraffin-embedded (FFPE) mouse tissue samples of lung, brain, heart, spleen, liver, kidney and intestine. 28334446 7 40 link linked 1339:1344 arg1 residues 1356:1363 alpha(1-3) linked galactose residues 1328:1363 alpha(1-3) linked galactose residues 1328:1363 Two of these latter ones also possessed alpha(1-3) linked galactose residues. 28334446 6 41 theme mannose 1175:1181 arg1 structures 1085:1094 Sixteen major N-linked carbohydrate structures 1049:1094 Sixteen major N-linked carbohydrate structures 1049:1094 Sixteen major N-linked carbohydrate structures were sequenced from the mouse lung FFPE tissue glycome and identified, as high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides. 28334446 6 41 theme mannose 1175:1181 arg1 oligosaccharides 1270:1285 high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides 1170:1285 high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides 1170:1285 Sixteen major N-linked carbohydrate structures were sequenced from the mouse lung FFPE tissue glycome and identified, as high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides. 28334446 5 42 theme associated 925:934 arg1 database 936:943 the associated database 921:943 the associated database 921:943 Structural assignment of the oligosaccharides was accomplished by the help of the GUcal software and the associated database, based on the mobility shifts after treatments with the corresponding exoglycosidase reaction mixtures. 28334446 6 43 theme N-linked 1063:1070 arg1 structures 1085:1094 Sixteen major N-linked carbohydrate structures 1049:1094 Sixteen major N-linked carbohydrate structures 1049:1094 Sixteen major N-linked carbohydrate structures were sequenced from the mouse lung FFPE tissue glycome and identified, as high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides. 28334446 6 43 theme N-linked 1063:1070 arg1 oligosaccharides 1270:1285 high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides 1170:1285 high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides 1170:1285 Sixteen major N-linked carbohydrate structures were sequenced from the mouse lung FFPE tissue glycome and identified, as high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides. 28334446 6 44 theme monoantennary 1222:1234 arg1 structures 1085:1094 Sixteen major N-linked carbohydrate structures 1049:1094 Sixteen major N-linked carbohydrate structures 1049:1094 Sixteen major N-linked carbohydrate structures were sequenced from the mouse lung FFPE tissue glycome and identified, as high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides. 28334446 6 44 theme monoantennary 1222:1234 arg1 oligosaccharides 1270:1285 high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides 1170:1285 high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides 1170:1285 Sixteen major N-linked carbohydrate structures were sequenced from the mouse lung FFPE tissue glycome and identified, as high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides. 28334446 4 45 theme lung 714:717 arg1 specimen 719:726 the lung specimen 710:726 the lung specimen 710:726 After CE-LIF glycoprofiling of the FFPE mouse tissues, the N-glycan pool of the lung specimen was subject to further investigation by exoglycosidase array based carbohydrate sequencing. 28334446 5 46 theme GUcal 902:906 arg1 software 908:915 the GUcal software 898:915 the GUcal software 898:915 Structural assignment of the oligosaccharides was accomplished by the help of the GUcal software and the associated database, based on the mobility shifts after treatments with the corresponding exoglycosidase reaction mixtures. 28334446 1 47 theme intestine 410:418 arg1 samples 353:359 formalin-fixed paraffin-embedded (FFPE) mouse tissue samples 300:359 formalin-fixed paraffin-embedded (FFPE) mouse tissue samples of lung, brain, heart, spleen, liver, kidney and intestine 300:418 Capillary electrophoresis with laser-induced fluorescence (CE-LIF) detection was used to analyze endoglycosidase released and fluorophore-labeled N-glycans from formalin-fixed paraffin-embedded (FFPE) mouse tissue samples of lung, brain, heart, spleen, liver, kidney and intestine. 28334446 4 48 theme N-glycan 693:700 arg1 pool 702:705 the N-glycan pool 689:705 the N-glycan pool of the lung specimen 689:726 After CE-LIF glycoprofiling of the FFPE mouse tissues, the N-glycan pool of the lung specimen was subject to further investigation by exoglycosidase array based carbohydrate sequencing. 28334446 4 48 theme N-glycan 693:700 arg1 subject 732:738 subject 732:738 subject 732:738 After CE-LIF glycoprofiling of the FFPE mouse tissues, the N-glycan pool of the lung specimen was subject to further investigation by exoglycosidase array based carbohydrate sequencing. 28334446 6 49 link N-linked 1063:1070 arg1 structures 1085:1094 Sixteen major N-linked carbohydrate structures 1049:1094 Sixteen major N-linked carbohydrate structures 1049:1094 Sixteen major N-linked carbohydrate structures were sequenced from the mouse lung FFPE tissue glycome and identified, as high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides. 28334446 6 49 link N-linked 1063:1070 arg1 oligosaccharides 1270:1285 high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides 1170:1285 high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides 1170:1285 Sixteen major N-linked carbohydrate structures were sequenced from the mouse lung FFPE tissue glycome and identified, as high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides. 28334446 6 50 theme lung 1126:1129 arg1 glycome 1143:1149 the mouse lung FFPE tissue glycome 1116:1149 the mouse lung FFPE tissue glycome 1116:1149 Sixteen major N-linked carbohydrate structures were sequenced from the mouse lung FFPE tissue glycome and identified, as high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides. 28334446 1 51 dep formalin-fixed 300:313 arg1 paraffin-embedded 315:331 paraffin-embedded 315:331 paraffin-embedded 315:331 Capillary electrophoresis with laser-induced fluorescence (CE-LIF) detection was used to analyze endoglycosidase released and fluorophore-labeled N-glycans from formalin-fixed paraffin-embedded (FFPE) mouse tissue samples of lung, brain, heart, spleen, liver, kidney and intestine. 28334446 4 52 theme exoglycosidase 768:781 arg1 sequencing 808:817 exoglycosidase array based carbohydrate sequencing 768:817 exoglycosidase array based carbohydrate sequencing 768:817 After CE-LIF glycoprofiling of the FFPE mouse tissues, the N-glycan pool of the lung specimen was subject to further investigation by exoglycosidase array based carbohydrate sequencing. 28334446 5 53 theme Structural 820:829 arg1 assignment 831:840 Structural assignment 820:840 Structural assignment of the oligosaccharides 820:864 Structural assignment of the oligosaccharides was accomplished by the help of the GUcal software and the associated database, based on the mobility shifts after treatments with the corresponding exoglycosidase reaction mixtures. 28334446 1 54 theme laser-induced 170:182 arg1 fluorescence 184:195 laser-induced fluorescence 170:195 laser-induced fluorescence (CE-LIF) detection 170:214 Capillary electrophoresis with laser-induced fluorescence (CE-LIF) detection was used to analyze endoglycosidase released and fluorophore-labeled N-glycans from formalin-fixed paraffin-embedded (FFPE) mouse tissue samples of lung, brain, heart, spleen, liver, kidney and intestine. 28334446 6 55 theme bianennary 1255:1264 arg1 structures 1085:1094 Sixteen major N-linked carbohydrate structures 1049:1094 Sixteen major N-linked carbohydrate structures 1049:1094 Sixteen major N-linked carbohydrate structures were sequenced from the mouse lung FFPE tissue glycome and identified, as high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides. 28334446 6 55 theme bianennary 1255:1264 arg1 oligosaccharides 1270:1285 high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides 1170:1285 high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides 1170:1285 Sixteen major N-linked carbohydrate structures were sequenced from the mouse lung FFPE tissue glycome and identified, as high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides. 28334446 6 56 dep oligosaccharides 1270:1285 arg1 3 1208:1208 3 1208:1208 3 1208:1208 Sixteen major N-linked carbohydrate structures were sequenced from the mouse lung FFPE tissue glycome and identified, as high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides. 28334446 0 57 theme formalin-fixed 84:97 arg1 samples 130:136 formalin-fixed paraffin-embedded mouse tissue samples 84:136 formalin-fixed paraffin-embedded mouse tissue samples 84:136 Molecular glycopathology by capillary electrophoresis: Analysis of the N-glycome of formalin-fixed paraffin-embedded mouse tissue samples. 28334446 1 58 theme heart 377:381 arg1 samples 353:359 formalin-fixed paraffin-embedded (FFPE) mouse tissue samples 300:359 formalin-fixed paraffin-embedded (FFPE) mouse tissue samples of lung, brain, heart, spleen, liver, kidney and intestine 300:418 Capillary electrophoresis with laser-induced fluorescence (CE-LIF) detection was used to analyze endoglycosidase released and fluorophore-labeled N-glycans from formalin-fixed paraffin-embedded (FFPE) mouse tissue samples of lung, brain, heart, spleen, liver, kidney and intestine. 28334446 5 59 theme mobility 959:966 arg1 shifts 968:973 the mobility shifts 955:973 the mobility shifts after treatments with the corresponding exoglycosidase reaction mixtures 955:1046 Structural assignment of the oligosaccharides was accomplished by the help of the GUcal software and the associated database, based on the mobility shifts after treatments with the corresponding exoglycosidase reaction mixtures. 28334446 0 60 theme mouse 117:121 arg1 samples 130:136 formalin-fixed paraffin-embedded mouse tissue samples 84:136 formalin-fixed paraffin-embedded mouse tissue samples 84:136 Molecular glycopathology by capillary electrophoresis: Analysis of the N-glycome of formalin-fixed paraffin-embedded mouse tissue samples. 28334446 1 61 theme spleen 384:389 arg1 samples 353:359 formalin-fixed paraffin-embedded (FFPE) mouse tissue samples 300:359 formalin-fixed paraffin-embedded (FFPE) mouse tissue samples of lung, brain, heart, spleen, liver, kidney and intestine 300:418 Capillary electrophoresis with laser-induced fluorescence (CE-LIF) detection was used to analyze endoglycosidase released and fluorophore-labeled N-glycans from formalin-fixed paraffin-embedded (FFPE) mouse tissue samples of lung, brain, heart, spleen, liver, kidney and intestine. 28334446 0 62 theme samples 130:136 arg1 N-glycome 71:79 the N-glycome 67:79 the N-glycome of formalin-fixed paraffin-embedded mouse tissue samples 67:136 Molecular glycopathology by capillary electrophoresis: Analysis of the N-glycome of formalin-fixed paraffin-embedded mouse tissue samples. 28334446 1 63 theme liver 392:396 arg1 samples 353:359 formalin-fixed paraffin-embedded (FFPE) mouse tissue samples 300:359 formalin-fixed paraffin-embedded (FFPE) mouse tissue samples of lung, brain, heart, spleen, liver, kidney and intestine 300:418 Capillary electrophoresis with laser-induced fluorescence (CE-LIF) detection was used to analyze endoglycosidase released and fluorophore-labeled N-glycans from formalin-fixed paraffin-embedded (FFPE) mouse tissue samples of lung, brain, heart, spleen, liver, kidney and intestine. 28334446 1 64 with electrophoresis 149:163 arg1 detection 206:214 laser-induced fluorescence (CE-LIF) detection 170:214 laser-induced fluorescence (CE-LIF) detection 170:214 Capillary electrophoresis with laser-induced fluorescence (CE-LIF) detection was used to analyze endoglycosidase released and fluorophore-labeled N-glycans from formalin-fixed paraffin-embedded (FFPE) mouse tissue samples of lung, brain, heart, spleen, liver, kidney and intestine. 28334446 1 64 with electrophoresis 149:163 arg1 CE-LIF 198:203 CE-LIF 198:203 CE-LIF 198:203 Capillary electrophoresis with laser-induced fluorescence (CE-LIF) detection was used to analyze endoglycosidase released and fluorophore-labeled N-glycans from formalin-fixed paraffin-embedded (FFPE) mouse tissue samples of lung, brain, heart, spleen, liver, kidney and intestine. 28334446 6 65 theme high 1170:1173 arg1 structures 1085:1094 Sixteen major N-linked carbohydrate structures 1049:1094 Sixteen major N-linked carbohydrate structures 1049:1094 Sixteen major N-linked carbohydrate structures were sequenced from the mouse lung FFPE tissue glycome and identified, as high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides. 28334446 6 65 theme high 1170:1173 arg1 oligosaccharides 1270:1285 high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides 1170:1285 high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides 1170:1285 Sixteen major N-linked carbohydrate structures were sequenced from the mouse lung FFPE tissue glycome and identified, as high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides. 28334446 1 66 theme kidney 399:404 arg1 samples 353:359 formalin-fixed paraffin-embedded (FFPE) mouse tissue samples 300:359 formalin-fixed paraffin-embedded (FFPE) mouse tissue samples of lung, brain, heart, spleen, liver, kidney and intestine 300:418 Capillary electrophoresis with laser-induced fluorescence (CE-LIF) detection was used to analyze endoglycosidase released and fluorophore-labeled N-glycans from formalin-fixed paraffin-embedded (FFPE) mouse tissue samples of lung, brain, heart, spleen, liver, kidney and intestine. 28334446 5 67 theme corresponding 1001:1013 arg1 mixtures 1039:1046 the corresponding exoglycosidase reaction mixtures 997:1046 the corresponding exoglycosidase reaction mixtures 997:1046 Structural assignment of the oligosaccharides was accomplished by the help of the GUcal software and the associated database, based on the mobility shifts after treatments with the corresponding exoglycosidase reaction mixtures. 28334446 7 68 contain possessed 1318:1326 arg1 ones 1308:1311 these latter ones 1295:1311 these latter ones 1295:1311 Two of these latter ones also possessed alpha(1-3) linked galactose residues. 28334446 7 68 contain possessed 1318:1326 arg2 residues 1356:1363 alpha(1-3) linked galactose residues 1328:1363 alpha(1-3) linked galactose residues 1328:1363 Two of these latter ones also possessed alpha(1-3) linked galactose residues. 28334446 7 68 contain possessed 1318:1326 arg1 Two 1288:1290 Two 1288:1290 Two 1288:1290 Two of these latter ones also possessed alpha(1-3) linked galactose residues. 28334446 5 69 with treatments 981:990 arg1 mixtures 1039:1046 the corresponding exoglycosidase reaction mixtures 997:1046 the corresponding exoglycosidase reaction mixtures 997:1046 Structural assignment of the oligosaccharides was accomplished by the help of the GUcal software and the associated database, based on the mobility shifts after treatments with the corresponding exoglycosidase reaction mixtures. 28334446 4 70 theme based 789:793 arg1 sequencing 808:817 exoglycosidase array based carbohydrate sequencing 768:817 exoglycosidase array based carbohydrate sequencing 768:817 After CE-LIF glycoprofiling of the FFPE mouse tissues, the N-glycan pool of the lung specimen was subject to further investigation by exoglycosidase array based carbohydrate sequencing. 28334446 0 71 theme capillary 28:36 arg1 electrophoresis 38:52 capillary electrophoresis 28:52 capillary electrophoresis 28:52 Molecular glycopathology by capillary electrophoresis: Analysis of the N-glycome of formalin-fixed paraffin-embedded mouse tissue samples. 28334446 1 72 theme mouse 340:344 arg1 samples 353:359 formalin-fixed paraffin-embedded (FFPE) mouse tissue samples 300:359 formalin-fixed paraffin-embedded (FFPE) mouse tissue samples of lung, brain, heart, spleen, liver, kidney and intestine 300:418 Capillary electrophoresis with laser-induced fluorescence (CE-LIF) detection was used to analyze endoglycosidase released and fluorophore-labeled N-glycans from formalin-fixed paraffin-embedded (FFPE) mouse tissue samples of lung, brain, heart, spleen, liver, kidney and intestine. 28334446 5 73 theme reaction 1030:1037 arg1 mixtures 1039:1046 the corresponding exoglycosidase reaction mixtures 997:1046 the corresponding exoglycosidase reaction mixtures 997:1046 Structural assignment of the oligosaccharides was accomplished by the help of the GUcal software and the associated database, based on the mobility shifts after treatments with the corresponding exoglycosidase reaction mixtures. 28334446 7 74 theme galactose 1346:1354 arg1 residues 1356:1363 alpha(1-3) linked galactose residues 1328:1363 alpha(1-3) linked galactose residues 1328:1363 Two of these latter ones also possessed alpha(1-3) linked galactose residues. 28334446 5 75 theme oligosaccharides 849:864 arg1 assignment 831:840 Structural assignment 820:840 Structural assignment of the oligosaccharides 820:864 Structural assignment of the oligosaccharides was accomplished by the help of the GUcal software and the associated database, based on the mobility shifts after treatments with the corresponding exoglycosidase reaction mixtures. 28334446 6 76 theme tissue 1136:1141 arg1 glycome 1143:1149 the mouse lung FFPE tissue glycome 1116:1149 the mouse lung FFPE tissue glycome 1116:1149 Sixteen major N-linked carbohydrate structures were sequenced from the mouse lung FFPE tissue glycome and identified, as high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides. 28334446 2 77 theme FFPE 425:428 arg1 samples 430:436 The FFPE samples 421:436 The FFPE samples 421:436 The FFPE samples were first deparaffinized followed by solubilization and glycoprotein retrieval. 28334446 2 77 theme FFPE 425:428 arg1 deparaffinized 449:462 deparaffinized 449:462 deparaffinized 449:462 The FFPE samples were first deparaffinized followed by solubilization and glycoprotein retrieval. 28334446 2 77 theme FFPE 425:428 arg1 followed 464:471 followed 464:471 followed by solubilization and glycoprotein retrieval 464:516 The FFPE samples were first deparaffinized followed by solubilization and glycoprotein retrieval. 28334446 1 78 theme lung 364:367 arg1 samples 353:359 formalin-fixed paraffin-embedded (FFPE) mouse tissue samples 300:359 formalin-fixed paraffin-embedded (FFPE) mouse tissue samples of lung, brain, heart, spleen, liver, kidney and intestine 300:418 Capillary electrophoresis with laser-induced fluorescence (CE-LIF) detection was used to analyze endoglycosidase released and fluorophore-labeled N-glycans from formalin-fixed paraffin-embedded (FFPE) mouse tissue samples of lung, brain, heart, spleen, liver, kidney and intestine. 28334446 1 79 theme brain 370:374 arg1 samples 353:359 formalin-fixed paraffin-embedded (FFPE) mouse tissue samples 300:359 formalin-fixed paraffin-embedded (FFPE) mouse tissue samples of lung, brain, heart, spleen, liver, kidney and intestine 300:418 Capillary electrophoresis with laser-induced fluorescence (CE-LIF) detection was used to analyze endoglycosidase released and fluorophore-labeled N-glycans from formalin-fixed paraffin-embedded (FFPE) mouse tissue samples of lung, brain, heart, spleen, liver, kidney and intestine. 28334446 6 80 theme biantennary 1195:1205 arg1 structures 1085:1094 Sixteen major N-linked carbohydrate structures 1049:1094 Sixteen major N-linked carbohydrate structures 1049:1094 Sixteen major N-linked carbohydrate structures were sequenced from the mouse lung FFPE tissue glycome and identified, as high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides. 28334446 6 80 theme biantennary 1195:1205 arg1 oligosaccharides 1270:1285 high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides 1170:1285 high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides 1170:1285 Sixteen major N-linked carbohydrate structures were sequenced from the mouse lung FFPE tissue glycome and identified, as high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides. 28334446 4 81 theme FFPE 669:672 arg1 tissues 680:686 the FFPE mouse tissues 665:686 the FFPE mouse tissues 665:686 After CE-LIF glycoprofiling of the FFPE mouse tissues, the N-glycan pool of the lung specimen was subject to further investigation by exoglycosidase array based carbohydrate sequencing. 28334446 1 82 dep released 252:259 arg1 endoglycosidase 236:250 endoglycosidase 236:250 endoglycosidase 236:250 Capillary electrophoresis with laser-induced fluorescence (CE-LIF) detection was used to analyze endoglycosidase released and fluorophore-labeled N-glycans from formalin-fixed paraffin-embedded (FFPE) mouse tissue samples of lung, brain, heart, spleen, liver, kidney and intestine. 28334446 3 83 theme F 526:526 arg1 release 537:543 PNGase F mediated release 519:543 PNGase F mediated release of the N-linked oligosaccharides 519:576 PNGase F mediated release of the N-linked oligosaccharides was followed by labeling with aminopyrene trisulfonate. 28334446 1 84 theme fluorophore-labeled 265:283 arg1 N-glycans 285:293 endoglycosidase released and fluorophore-labeled N-glycans 236:293 endoglycosidase released and fluorophore-labeled N-glycans from formalin-fixed paraffin-embedded (FFPE) mouse tissue samples of lung, brain, heart, spleen, liver, kidney and intestine 236:418 Capillary electrophoresis with laser-induced fluorescence (CE-LIF) detection was used to analyze endoglycosidase released and fluorophore-labeled N-glycans from formalin-fixed paraffin-embedded (FFPE) mouse tissue samples of lung, brain, heart, spleen, liver, kidney and intestine. 28334446 0 85 dep glycopathology 10:23 arg1 Analysis 55:62 Analysis 55:62 Molecular glycopathology by capillary electrophoresis: Analysis of the N-glycome of formalin-fixed paraffin-embedded mouse tissue samples. 0:137 Molecular glycopathology by capillary electrophoresis: Analysis of the N-glycome of formalin-fixed paraffin-embedded mouse tissue samples. 28334446 7 86 theme ones 1308:1311 arg1 ones 1308:1311 these latter ones 1295:1311 these latter ones 1295:1311 Two of these latter ones also possessed alpha(1-3) linked galactose residues. 28334446 7 86 theme ones 1308:1311 arg1 Two 1288:1290 Two 1288:1290 Two 1288:1290 Two of these latter ones also possessed alpha(1-3) linked galactose residues. 28334446 4 87 theme tissues 680:686 arg1 glycoprofiling 647:660 CE-LIF glycoprofiling 640:660 CE-LIF glycoprofiling of the FFPE mouse tissues 640:686 After CE-LIF glycoprofiling of the FFPE mouse tissues, the N-glycan pool of the lung specimen was subject to further investigation by exoglycosidase array based carbohydrate sequencing. 28334446 3 88 theme oligosaccharides 561:576 arg1 release 537:543 PNGase F mediated release 519:543 PNGase F mediated release of the N-linked oligosaccharides 519:576 PNGase F mediated release of the N-linked oligosaccharides was followed by labeling with aminopyrene trisulfonate. 27084943 3 0 theme search 671:676 arg1 engine 678:683 a database search engine 660:683 a database search engine (e.g. Mascot) 660:697 MAGIC is implemented with our previously proposed novel Y1-ion pattern matching method, which adequately detects Y1- and Y0-ion without prior information of proteins and glycans, and then generates in silico MS(2) spectra that serve as input to a database search engine (e.g. Mascot) to search against a large-scale protein sequence database. 27084943 3 0 theme search 671:676 arg1 Mascot 691:696 Mascot 691:696 Mascot 691:696 MAGIC is implemented with our previously proposed novel Y1-ion pattern matching method, which adequately detects Y1- and Y0-ion without prior information of proteins and glycans, and then generates in silico MS(2) spectra that serve as input to a database search engine (e.g. Mascot) to search against a large-scale protein sequence database. 27084943 3 1 theme in 613:614 arg1 2 626:626 2 626:626 2 626:626 MAGIC is implemented with our previously proposed novel Y1-ion pattern matching method, which adequately detects Y1- and Y0-ion without prior information of proteins and glycans, and then generates in silico MS(2) spectra that serve as input to a database search engine (e.g. Mascot) to search against a large-scale protein sequence database. 27084943 3 1 theme in 613:614 arg1 MS 623:624 in silico MS 613:624 in silico MS(2) spectra that serve as input to a database search engine (e.g. Mascot) to search against a large-scale protein sequence database 613:755 MAGIC is implemented with our previously proposed novel Y1-ion pattern matching method, which adequately detects Y1- and Y0-ion without prior information of proteins and glycans, and then generates in silico MS(2) spectra that serve as input to a database search engine (e.g. Mascot) to search against a large-scale protein sequence database. 27084943 1 2 theme glycoproteomics 232:246 arg1 analyses 196:203 targeted analyses 187:203 targeted analyses of mass spectrometry-based glycoproteomics 187:246 MAGIC-web is the first web server, to the best of our knowledge, that performs both untargeted and targeted analyses of mass spectrometry-based glycoproteomics data for site-specific N-linked glycoprotein identification. 27084943 6 3 theme specific 1240:1247 arg1 numbers 1249:1255 specific numbers 1240:1255 specific numbers 1240:1255 The last module, Glycan Search, is designed for the users who are interested in finding possible glycan structures with specific numbers and types of monosaccharides. 27084943 4 4 theme glycopeptide 829:840 arg1 sequences 842:850 glycopeptide sequences 829:850 glycopeptide sequences using their own protein sequence file 829:888 On top of that, the newly implemented MAGIC+ allows users to determine glycopeptide sequences using their own protein sequence file. 27084943 7 5 dep MAGIC 1304:1308 arg1 Integrator 1330:1339 Integrator 1330:1339 Integrator 1330:1339 The results from MAGIC, MAGIC+ and Reports Integrator can be downloaded via provided links whereas the annotated spectra and glycan structures can be visualized in the browser. 27084943 5 6 theme Reports 909:915 arg1 module 901:906 The third module 891:906 The third module 891:906 The third module, Reports Integrator, provides the service of combining protein identification results from Mascot and glycan-related information from MAGIC-web to generate a complete site-specific protein-glycan summary report. 27084943 5 6 theme Reports 909:915 arg1 Integrator 917:926 Reports Integrator 909:926 Reports Integrator 909:926 The third module, Reports Integrator, provides the service of combining protein identification results from Mascot and glycan-related information from MAGIC-web to generate a complete site-specific protein-glycan summary report. 27084943 6 7 theme last 1124:1127 arg1 module 1129:1134 The last module 1120:1134 The last module 1120:1134 The last module, Glycan Search, is designed for the users who are interested in finding possible glycan structures with specific numbers and types of monosaccharides. 27084943 6 7 theme last 1124:1127 arg1 Search 1144:1149 Glycan Search 1137:1149 Glycan Search 1137:1149 The last module, Glycan Search, is designed for the users who are interested in finding possible glycan structures with specific numbers and types of monosaccharides. 27084943 6 8 theme Glycan 1137:1142 arg1 module 1129:1134 The last module 1120:1134 The last module 1120:1134 The last module, Glycan Search, is designed for the users who are interested in finding possible glycan structures with specific numbers and types of monosaccharides. 27084943 6 8 theme Glycan 1137:1142 arg1 Search 1144:1149 Glycan Search 1137:1149 Glycan Search 1137:1149 The last module, Glycan Search, is designed for the users who are interested in finding possible glycan structures with specific numbers and types of monosaccharides. 27084943 3 9 theme prior 551:555 arg1 information 557:567 prior information 551:567 prior information of proteins and glycans 551:591 MAGIC is implemented with our previously proposed novel Y1-ion pattern matching method, which adequately detects Y1- and Y0-ion without prior information of proteins and glycans, and then generates in silico MS(2) spectra that serve as input to a database search engine (e.g. Mascot) to search against a large-scale protein sequence database. 27084943 0 10 gly glycoprotein 59:70 arg1 glycoprotein 59:70 untargeted and targeted N-linked glycoprotein identification 26:85 untargeted and targeted N-linked glycoprotein identification 26:85 MAGIC-web: a platform for untargeted and targeted N-linked glycoprotein identification. 27084943 7 11 from MAGIC+ 1311:1316 arg1 results 1291:1297 The results 1287:1297 The results from MAGIC, MAGIC+ and Reports Integrator 1287:1339 The results from MAGIC, MAGIC+ and Reports Integrator can be downloaded via provided links whereas the annotated spectra and glycan structures can be visualized in the browser. 27084943 1 12 theme site-specific 257:269 arg1 identification 293:306 site-specific N-linked glycoprotein identification 257:306 site-specific N-linked glycoprotein identification 257:306 MAGIC-web is the first web server, to the best of our knowledge, that performs both untargeted and targeted analyses of mass spectrometry-based glycoproteomics data for site-specific N-linked glycoprotein identification. 27084943 2 13 theme MAGIC+ 342:347 arg1 modules 323:329 The first two modules 309:329 The first two modules 309:329 The first two modules, MAGIC and MAGIC+, are designed for untargeted and targeted analysis, respectively. 27084943 4 14 theme implemented 784:794 arg1 MAGIC+ 796:801 the newly implemented MAGIC+ 774:801 the newly implemented MAGIC+ 774:801 On top of that, the newly implemented MAGIC+ allows users to determine glycopeptide sequences using their own protein sequence file. 27084943 3 15 dep in 613:614 arg1 silico 616:621 silico 616:621 silico 616:621 MAGIC is implemented with our previously proposed novel Y1-ion pattern matching method, which adequately detects Y1- and Y0-ion without prior information of proteins and glycans, and then generates in silico MS(2) spectra that serve as input to a database search engine (e.g. Mascot) to search against a large-scale protein sequence database. 27084943 7 16 theme annotated 1390:1398 arg1 spectra 1400:1406 the annotated spectra 1386:1406 the annotated spectra 1386:1406 The results from MAGIC, MAGIC+ and Reports Integrator can be downloaded via provided links whereas the annotated spectra and glycan structures can be visualized in the browser. 27084943 5 17 from MAGIC-web 1042:1050 arg1 information 1025:1035 Mascot and glycan-related information 999:1035 Mascot and glycan-related information from MAGIC-web to generate a complete site-specific protein-glycan summary report 999:1117 The third module, Reports Integrator, provides the service of combining protein identification results from Mascot and glycan-related information from MAGIC-web to generate a complete site-specific protein-glycan summary report. 27084943 5 18 theme site-specific 1075:1087 arg1 report 1112:1117 a complete site-specific protein-glycan summary report 1064:1117 a complete site-specific protein-glycan summary report 1064:1117 The third module, Reports Integrator, provides the service of combining protein identification results from Mascot and glycan-related information from MAGIC-web to generate a complete site-specific protein-glycan summary report. 27084943 7 19 from Reports 1322:1328 arg1 results 1291:1297 The results 1287:1297 The results from MAGIC, MAGIC+ and Reports Integrator 1287:1339 The results from MAGIC, MAGIC+ and Reports Integrator can be downloaded via provided links whereas the annotated spectra and glycan structures can be visualized in the browser. 27084943 2 20 theme targeted 382:389 arg1 analysis 391:398 untargeted and targeted analysis 367:398 untargeted and targeted analysis 367:398 The first two modules, MAGIC and MAGIC+, are designed for untargeted and targeted analysis, respectively. 27084943 5 21 theme protein-glycan 1089:1102 arg1 report 1112:1117 a complete site-specific protein-glycan summary report 1064:1117 a complete site-specific protein-glycan summary report 1064:1117 The third module, Reports Integrator, provides the service of combining protein identification results from Mascot and glycan-related information from MAGIC-web to generate a complete site-specific protein-glycan summary report. 27084943 6 22 theme glycan 1217:1222 arg1 structures 1224:1233 possible glycan structures 1208:1233 possible glycan structures 1208:1233 The last module, Glycan Search, is designed for the users who are interested in finding possible glycan structures with specific numbers and types of monosaccharides. 27084943 3 23 theme proteins 572:579 arg1 information 557:567 prior information 551:567 prior information of proteins and glycans 551:591 MAGIC is implemented with our previously proposed novel Y1-ion pattern matching method, which adequately detects Y1- and Y0-ion without prior information of proteins and glycans, and then generates in silico MS(2) spectra that serve as input to a database search engine (e.g. Mascot) to search against a large-scale protein sequence database. 27084943 5 24 theme complete 1066:1073 arg1 report 1112:1117 a complete site-specific protein-glycan summary report 1064:1117 a complete site-specific protein-glycan summary report 1064:1117 The third module, Reports Integrator, provides the service of combining protein identification results from Mascot and glycan-related information from MAGIC-web to generate a complete site-specific protein-glycan summary report. 27084943 1 25 theme N-linked 271:278 arg1 identification 293:306 site-specific N-linked glycoprotein identification 257:306 site-specific N-linked glycoprotein identification 257:306 MAGIC-web is the first web server, to the best of our knowledge, that performs both untargeted and targeted analyses of mass spectrometry-based glycoproteomics data for site-specific N-linked glycoprotein identification. 27084943 6 26 theme possible 1208:1215 arg1 structures 1224:1233 possible glycan structures 1208:1233 possible glycan structures 1208:1233 The last module, Glycan Search, is designed for the users who are interested in finding possible glycan structures with specific numbers and types of monosaccharides. 27084943 5 27 theme third 895:899 arg1 module 901:906 The third module 891:906 The third module 891:906 The third module, Reports Integrator, provides the service of combining protein identification results from Mascot and glycan-related information from MAGIC-web to generate a complete site-specific protein-glycan summary report. 27084943 5 27 theme third 895:899 arg1 Integrator 917:926 Reports Integrator 909:926 Reports Integrator 909:926 The third module, Reports Integrator, provides the service of combining protein identification results from Mascot and glycan-related information from MAGIC-web to generate a complete site-specific protein-glycan summary report. 27084943 2 28 theme untargeted 367:376 arg1 analysis 391:398 untargeted and targeted analysis 367:398 untargeted and targeted analysis 367:398 The first two modules, MAGIC and MAGIC+, are designed for untargeted and targeted analysis, respectively. 27084943 1 29 theme glycoprotein 280:291 arg1 identification 293:306 site-specific N-linked glycoprotein identification 257:306 site-specific N-linked glycoprotein identification 257:306 MAGIC-web is the first web server, to the best of our knowledge, that performs both untargeted and targeted analyses of mass spectrometry-based glycoproteomics data for site-specific N-linked glycoprotein identification. 27084943 4 30 theme sequence 876:883 arg1 file 885:888 their own protein sequence file 858:888 their own protein sequence file 858:888 On top of that, the newly implemented MAGIC+ allows users to determine glycopeptide sequences using their own protein sequence file. 27084943 2 31 theme first 313:317 arg1 modules 323:329 The first two modules 309:329 The first two modules 309:329 The first two modules, MAGIC and MAGIC+, are designed for untargeted and targeted analysis, respectively. 27084943 3 32 theme novel 465:469 arg1 pattern 478:484 our previously proposed novel Y1-ion pattern 441:484 our previously proposed novel Y1-ion pattern matching method, which adequately detects Y1- and Y0-ion without prior information of proteins and glycans 441:591 MAGIC is implemented with our previously proposed novel Y1-ion pattern matching method, which adequately detects Y1- and Y0-ion without prior information of proteins and glycans, and then generates in silico MS(2) spectra that serve as input to a database search engine (e.g. Mascot) to search against a large-scale protein sequence database. 27084943 4 33 theme protein 868:874 arg1 file 885:888 their own protein sequence file 858:888 their own protein sequence file 858:888 On top of that, the newly implemented MAGIC+ allows users to determine glycopeptide sequences using their own protein sequence file. 27084943 1 34 theme first 105:109 arg1 server 115:120 the first web server 101:120 the first web server 101:120 MAGIC-web is the first web server, to the best of our knowledge, that performs both untargeted and targeted analyses of mass spectrometry-based glycoproteomics data for site-specific N-linked glycoprotein identification. 27084943 1 34 theme first 105:109 arg1 MAGIC-web 88:96 MAGIC-web 88:96 MAGIC-web 88:96 MAGIC-web is the first web server, to the best of our knowledge, that performs both untargeted and targeted analyses of mass spectrometry-based glycoproteomics data for site-specific N-linked glycoprotein identification. 27084943 3 35 theme Y1-ion 471:476 arg1 pattern 478:484 our previously proposed novel Y1-ion pattern 441:484 our previously proposed novel Y1-ion pattern matching method, which adequately detects Y1- and Y0-ion without prior information of proteins and glycans 441:591 MAGIC is implemented with our previously proposed novel Y1-ion pattern matching method, which adequately detects Y1- and Y0-ion without prior information of proteins and glycans, and then generates in silico MS(2) spectra that serve as input to a database search engine (e.g. Mascot) to search against a large-scale protein sequence database. 27084943 0 36 theme untargeted 26:35 arg1 identification 72:85 untargeted and targeted N-linked glycoprotein identification 26:85 untargeted and targeted N-linked glycoprotein identification 26:85 MAGIC-web: a platform for untargeted and targeted N-linked glycoprotein identification. 27084943 8 37 dep http 1493:1496 arg1 //ms.iis.sinica.edu.tw/MAGIC-web/index.html 1498:1540 //ms.iis.sinica.edu.tw/MAGIC-web/index.html 1498:1540 http://ms.iis.sinica.edu.tw/MAGIC-web/index.html 1493:1540 MAGIC-web is accessible from http://ms.iis.sinica.edu.tw/MAGIC-web/index.html. 27084943 5 38 theme protein 963:969 arg1 identification 971:984 protein identification 963:984 protein identification 963:984 The third module, Reports Integrator, provides the service of combining protein identification results from Mascot and glycan-related information from MAGIC-web to generate a complete site-specific protein-glycan summary report. 27084943 4 39 gly glycopeptide 829:840 arg2 glycopeptide 829:840 glycopeptide sequences 829:850 glycopeptide sequences using their own protein sequence file 829:888 On top of that, the newly implemented MAGIC+ allows users to determine glycopeptide sequences using their own protein sequence file. 27084943 7 40 theme glycan 1412:1417 arg1 structures 1419:1428 glycan structures 1412:1428 glycan structures 1412:1428 The results from MAGIC, MAGIC+ and Reports Integrator can be downloaded via provided links whereas the annotated spectra and glycan structures can be visualized in the browser. 27084943 3 41 theme protein 731:737 arg1 database 748:755 a large-scale protein sequence database 717:755 a large-scale protein sequence database 717:755 MAGIC is implemented with our previously proposed novel Y1-ion pattern matching method, which adequately detects Y1- and Y0-ion without prior information of proteins and glycans, and then generates in silico MS(2) spectra that serve as input to a database search engine (e.g. Mascot) to search against a large-scale protein sequence database. 27084943 3 42 dep Mascot 691:696 arg1 e.g. 686:689 e.g. 686:689 e.g. 686:689 MAGIC is implemented with our previously proposed novel Y1-ion pattern matching method, which adequately detects Y1- and Y0-ion without prior information of proteins and glycans, and then generates in silico MS(2) spectra that serve as input to a database search engine (e.g. Mascot) to search against a large-scale protein sequence database. 27084943 1 43 gly glycoprotein 280:291 arg1 glycoprotein 280:291 site-specific N-linked glycoprotein identification 257:306 site-specific N-linked glycoprotein identification 257:306 MAGIC-web is the first web server, to the best of our knowledge, that performs both untargeted and targeted analyses of mass spectrometry-based glycoproteomics data for site-specific N-linked glycoprotein identification. 27084943 1 44 theme targeted 187:194 arg1 analyses 196:203 targeted analyses 187:203 targeted analyses of mass spectrometry-based glycoproteomics 187:246 MAGIC-web is the first web server, to the best of our knowledge, that performs both untargeted and targeted analyses of mass spectrometry-based glycoproteomics data for site-specific N-linked glycoprotein identification. 27084943 0 45 theme targeted 41:48 arg1 identification 72:85 untargeted and targeted N-linked glycoprotein identification 26:85 untargeted and targeted N-linked glycoprotein identification 26:85 MAGIC-web: a platform for untargeted and targeted N-linked glycoprotein identification. 27084943 3 46 theme sequence 739:746 arg1 database 748:755 a large-scale protein sequence database 717:755 a large-scale protein sequence database 717:755 MAGIC is implemented with our previously proposed novel Y1-ion pattern matching method, which adequately detects Y1- and Y0-ion without prior information of proteins and glycans, and then generates in silico MS(2) spectra that serve as input to a database search engine (e.g. Mascot) to search against a large-scale protein sequence database. 27084943 3 47 theme glycans 585:591 arg1 information 557:567 prior information 551:567 prior information of proteins and glycans 551:591 MAGIC is implemented with our previously proposed novel Y1-ion pattern matching method, which adequately detects Y1- and Y0-ion without prior information of proteins and glycans, and then generates in silico MS(2) spectra that serve as input to a database search engine (e.g. Mascot) to search against a large-scale protein sequence database. 27084943 6 48 theme monosaccharides 1270:1284 arg1 numbers 1249:1255 specific numbers 1240:1255 specific numbers 1240:1255 The last module, Glycan Search, is designed for the users who are interested in finding possible glycan structures with specific numbers and types of monosaccharides. 27084943 6 48 theme monosaccharides 1270:1284 arg1 types 1261:1265 types 1261:1265 types 1261:1265 The last module, Glycan Search, is designed for the users who are interested in finding possible glycan structures with specific numbers and types of monosaccharides. 27084943 1 49 theme web 111:113 arg1 server 115:120 the first web server 101:120 the first web server 101:120 MAGIC-web is the first web server, to the best of our knowledge, that performs both untargeted and targeted analyses of mass spectrometry-based glycoproteomics data for site-specific N-linked glycoprotein identification. 27084943 1 49 theme web 111:113 arg1 MAGIC-web 88:96 MAGIC-web 88:96 MAGIC-web 88:96 MAGIC-web is the first web server, to the best of our knowledge, that performs both untargeted and targeted analyses of mass spectrometry-based glycoproteomics data for site-specific N-linked glycoprotein identification. 27084943 8 50 from http 1493:1496 arg1 accessible 1477:1486 accessible 1477:1486 accessible 1477:1486 MAGIC-web is accessible from http://ms.iis.sinica.edu.tw/MAGIC-web/index.html. 27084943 5 51 theme summary 1104:1110 arg1 report 1112:1117 a complete site-specific protein-glycan summary report 1064:1117 a complete site-specific protein-glycan summary report 1064:1117 The third module, Reports Integrator, provides the service of combining protein identification results from Mascot and glycan-related information from MAGIC-web to generate a complete site-specific protein-glycan summary report. 27084943 5 52 theme Mascot 999:1004 arg1 information 1025:1035 Mascot and glycan-related information 999:1035 Mascot and glycan-related information from MAGIC-web to generate a complete site-specific protein-glycan summary report 999:1117 The third module, Reports Integrator, provides the service of combining protein identification results from Mascot and glycan-related information from MAGIC-web to generate a complete site-specific protein-glycan summary report. 27084943 0 53 dep MAGIC-web 0:8 arg1 platform 13:20 a platform 11:20 MAGIC-web: a platform for untargeted and targeted N-linked glycoprotein identification. 0:86 MAGIC-web: a platform for untargeted and targeted N-linked glycoprotein identification. 27084943 4 54 theme own 864:866 arg1 file 885:888 their own protein sequence file 858:888 their own protein sequence file 858:888 On top of that, the newly implemented MAGIC+ allows users to determine glycopeptide sequences using their own protein sequence file. 27084943 0 55 link N-linked 50:57 arg1 identification 72:85 untargeted and targeted N-linked glycoprotein identification 26:85 untargeted and targeted N-linked glycoprotein identification 26:85 MAGIC-web: a platform for untargeted and targeted N-linked glycoprotein identification. 27084943 2 56 theme MAGIC 332:336 arg1 modules 323:329 The first two modules 309:329 The first two modules 309:329 The first two modules, MAGIC and MAGIC+, are designed for untargeted and targeted analysis, respectively. 27084943 7 57 theme provided 1363:1370 arg1 links 1372:1376 provided links 1363:1376 provided links whereas the annotated spectra 1363:1406 The results from MAGIC, MAGIC+ and Reports Integrator can be downloaded via provided links whereas the annotated spectra and glycan structures can be visualized in the browser. 27084943 3 58 theme large-scale 719:729 arg1 database 748:755 a large-scale protein sequence database 717:755 a large-scale protein sequence database 717:755 MAGIC is implemented with our previously proposed novel Y1-ion pattern matching method, which adequately detects Y1- and Y0-ion without prior information of proteins and glycans, and then generates in silico MS(2) spectra that serve as input to a database search engine (e.g. Mascot) to search against a large-scale protein sequence database. 27084943 5 59 theme glycan-related 1010:1023 arg1 information 1025:1035 Mascot and glycan-related information 999:1035 Mascot and glycan-related information from MAGIC-web to generate a complete site-specific protein-glycan summary report 999:1117 The third module, Reports Integrator, provides the service of combining protein identification results from Mascot and glycan-related information from MAGIC-web to generate a complete site-specific protein-glycan summary report. 27084943 3 60 theme MS 623:624 arg1 spectra 629:635 in silico MS(2) spectra 613:635 in silico MS(2) spectra that serve as input to a database search engine (e.g. Mascot) to search against a large-scale protein sequence database 613:755 MAGIC is implemented with our previously proposed novel Y1-ion pattern matching method, which adequately detects Y1- and Y0-ion without prior information of proteins and glycans, and then generates in silico MS(2) spectra that serve as input to a database search engine (e.g. Mascot) to search against a large-scale protein sequence database. 27084943 0 61 theme glycoprotein 59:70 arg1 identification 72:85 untargeted and targeted N-linked glycoprotein identification 26:85 untargeted and targeted N-linked glycoprotein identification 26:85 MAGIC-web: a platform for untargeted and targeted N-linked glycoprotein identification. 27084943 3 62 theme proposed 456:463 arg1 pattern 478:484 our previously proposed novel Y1-ion pattern 441:484 our previously proposed novel Y1-ion pattern matching method, which adequately detects Y1- and Y0-ion without prior information of proteins and glycans 441:591 MAGIC is implemented with our previously proposed novel Y1-ion pattern matching method, which adequately detects Y1- and Y0-ion without prior information of proteins and glycans, and then generates in silico MS(2) spectra that serve as input to a database search engine (e.g. Mascot) to search against a large-scale protein sequence database. 27084943 7 63 from MAGIC 1304:1308 arg1 results 1291:1297 The results 1287:1297 The results from MAGIC, MAGIC+ and Reports Integrator 1287:1339 The results from MAGIC, MAGIC+ and Reports Integrator can be downloaded via provided links whereas the annotated spectra and glycan structures can be visualized in the browser. 27084943 0 64 theme N-linked 50:57 arg1 identification 72:85 untargeted and targeted N-linked glycoprotein identification 26:85 untargeted and targeted N-linked glycoprotein identification 26:85 MAGIC-web: a platform for untargeted and targeted N-linked glycoprotein identification. 27084943 3 65 theme database 662:669 arg1 engine 678:683 a database search engine 660:683 a database search engine (e.g. Mascot) 660:697 MAGIC is implemented with our previously proposed novel Y1-ion pattern matching method, which adequately detects Y1- and Y0-ion without prior information of proteins and glycans, and then generates in silico MS(2) spectra that serve as input to a database search engine (e.g. Mascot) to search against a large-scale protein sequence database. 27084943 3 65 theme database 662:669 arg1 Mascot 691:696 Mascot 691:696 Mascot 691:696 MAGIC is implemented with our previously proposed novel Y1-ion pattern matching method, which adequately detects Y1- and Y0-ion without prior information of proteins and glycans, and then generates in silico MS(2) spectra that serve as input to a database search engine (e.g. Mascot) to search against a large-scale protein sequence database. 27084943 1 66 dep untargeted 172:181 arg1 data 248:251 data 248:251 data 248:251 MAGIC-web is the first web server, to the best of our knowledge, that performs both untargeted and targeted analyses of mass spectrometry-based glycoproteomics data for site-specific N-linked glycoprotein identification. 27084943 1 67 link N-linked 271:278 arg1 identification 293:306 site-specific N-linked glycoprotein identification 257:306 site-specific N-linked glycoprotein identification 257:306 MAGIC-web is the first web server, to the best of our knowledge, that performs both untargeted and targeted analyses of mass spectrometry-based glycoproteomics data for site-specific N-linked glycoprotein identification. 27084943 1 68 theme spectrometry-based 213:230 arg1 glycoproteomics 232:246 mass spectrometry-based glycoproteomics 208:246 mass spectrometry-based glycoproteomics 208:246 MAGIC-web is the first web server, to the best of our knowledge, that performs both untargeted and targeted analyses of mass spectrometry-based glycoproteomics data for site-specific N-linked glycoprotein identification. 25274627 4 0 theme GnT-V 809:813 arg1 knock-out 796:804 knock-out 796:804 knock-out of GnT-V 796:813 Using Apc(min/+) mice with different GnT-V backgrounds, knock-out of GnT-V had no significant effect on the number of adenoma/mouse, but adenoma size was significantly reduced and accompanied increased survival of Apc(min/+) mice with GnT-V deletion (p < 0.01), suggesting an inhibition in the progression of colon adenoma caused by deletion of GnT-V. 25274627 1 1 with N-glycans 213:221 arg1 glycans 244:250 β(1,6)-branched glycans 228:250 β(1,6)-branched glycans 228:250 Deletion of GnT-V (MGAT5), which synthesizes N-glycans with β(1,6)-branched glycans, reduced the compartment of cancer stem cells (CSC) in the her-2 mouse model of breast cancer, leading to delay of tumor onset. 25274627 8 2 theme Wnt 1812:1814 arg1 signaling 1816:1824 Wnt signaling 1812:1824 Wnt signaling 1812:1824 The aberrant Wnt signaling observed after modulating GnT-V levels is likely to result from altered N-linked β(1,6) branching on FZD-7, thereby affecting Wnt signaling, the compartment of CSC, and tumor progression. 25274627 3 3 theme NOD/SCID 621:628 arg1 mice 630:633 NOD/SCID mice 621:633 NOD/SCID mice 621:633 Anchorage-independent cell growth and tumor formation induced by injection of colon tumor cells into NOD/SCID mice were positively associated with GnT-V levels, indicating regulation of proliferation and tumorigenicity. 25274627 5 4 theme expression 1102:1111 arg1 levels 1113:1118 Decreased expression levels 1092:1118 Decreased expression levels of GnT-V 1092:1127 Decreased expression levels of GnT-V down-regulated the population of colon (intestine) CSC, affecting their ability for self-renewal and tumorigenicity in NOD/SCID mice. 25274627 3 5 theme GnT-V 667:671 arg1 levels 673:678 GnT-V levels 667:678 GnT-V levels 667:678 Anchorage-independent cell growth and tumor formation induced by injection of colon tumor cells into NOD/SCID mice were positively associated with GnT-V levels, indicating regulation of proliferation and tumorigenicity. 25274627 8 6 theme N-linked 1758:1765 arg1 1,6 1769:1771 1,6 1769:1771 1,6 1769:1771 The aberrant Wnt signaling observed after modulating GnT-V levels is likely to result from altered N-linked β(1,6) branching on FZD-7, thereby affecting Wnt signaling, the compartment of CSC, and tumor progression. 25274627 8 6 theme N-linked 1758:1765 arg1 β 1767:1767 altered N-linked β 1750:1767 altered N-linked β(1,6) branching on FZD-7 1750:1791 The aberrant Wnt signaling observed after modulating GnT-V levels is likely to result from altered N-linked β(1,6) branching on FZD-7, thereby affecting Wnt signaling, the compartment of CSC, and tumor progression. 25274627 1 7 theme onset 373:377 arg1 delay 358:362 delay 358:362 delay of tumor onset 358:377 Deletion of GnT-V (MGAT5), which synthesizes N-glycans with β(1,6)-branched glycans, reduced the compartment of cancer stem cells (CSC) in the her-2 mouse model of breast cancer, leading to delay of tumor onset. 25274627 1 8 theme -branched 234:242 arg1 glycans 244:250 β(1,6)-branched glycans 228:250 β(1,6)-branched glycans 228:250 Deletion of GnT-V (MGAT5), which synthesizes N-glycans with β(1,6)-branched glycans, reduced the compartment of cancer stem cells (CSC) in the her-2 mouse model of breast cancer, leading to delay of tumor onset. 25274627 0 9 theme Post-translational 0:17 arg1 modifications 32:44 Post-translational glycoprotein modifications 0:44 Post-translational glycoprotein modifications 0:44 Post-translational glycoprotein modifications regulate colon cancer stem cells and colon adenoma progression in Apc(min/+) mice through altered Wnt receptor signaling. 25274627 6 10 theme Wnt/β-catenin 1453:1465 arg1 signaling 1467:1475 canonical Wnt/β-catenin signaling 1443:1475 canonical Wnt/β-catenin signaling 1443:1475 Furthermore, altered nuclear translocation of β-catenin and expression of Wnt target genes were positively associated with expression levels of GnT-V, indicating the regulation of canonical Wnt/β-catenin signaling. 25274627 7 11 mod modified 1640:1647 arg3 GnT-V 1652:1656 GnT-V 1652:1656 GnT-V 1652:1656 By overexpressing the Wnt receptor, FZD-7, in colon cancer cells, we found that FZD-7 receptors expressed N-linked β(1,6) branching, indicating that FZD-7 can be modified by GnT-V. 25274627 7 11 mod modified 1640:1647 arg1 FZD-7 1627:1631 FZD-7 1627:1631 FZD-7 1627:1631 By overexpressing the Wnt receptor, FZD-7, in colon cancer cells, we found that FZD-7 receptors expressed N-linked β(1,6) branching, indicating that FZD-7 can be modified by GnT-V. 25274627 3 12 theme tumorigenicity 724:737 arg1 regulation 692:701 regulation 692:701 regulation of proliferation and tumorigenicity 692:737 Anchorage-independent cell growth and tumor formation induced by injection of colon tumor cells into NOD/SCID mice were positively associated with GnT-V levels, indicating regulation of proliferation and tumorigenicity. 25274627 1 13 theme breast 332:337 arg1 cancer 339:344 breast cancer 332:344 breast cancer 332:344 Deletion of GnT-V (MGAT5), which synthesizes N-glycans with β(1,6)-branched glycans, reduced the compartment of cancer stem cells (CSC) in the her-2 mouse model of breast cancer, leading to delay of tumor onset. 25274627 3 14 theme cell 542:545 arg1 growth 547:552 Anchorage-independent cell growth 520:552 Anchorage-independent cell growth 520:552 Anchorage-independent cell growth and tumor formation induced by injection of colon tumor cells into NOD/SCID mice were positively associated with GnT-V levels, indicating regulation of proliferation and tumorigenicity. 25274627 2 15 theme adenoma 499:505 arg1 development 507:517 adenoma development 499:517 adenoma development 499:517 Because GnT-V levels are also commonly up-regulated in colon cancer, we investigated their regulation of colon CSC and adenoma development. 25274627 3 16 theme proliferation 706:718 arg1 regulation 692:701 regulation 692:701 regulation of proliferation and tumorigenicity 692:737 Anchorage-independent cell growth and tumor formation induced by injection of colon tumor cells into NOD/SCID mice were positively associated with GnT-V levels, indicating regulation of proliferation and tumorigenicity. 25274627 0 17 theme Wnt 144:146 arg1 signaling 157:165 altered Wnt receptor signaling 136:165 altered Wnt receptor signaling 136:165 Post-translational glycoprotein modifications regulate colon cancer stem cells and colon adenoma progression in Apc(min/+) mice through altered Wnt receptor signaling. 25274627 7 18 theme colon 1524:1528 arg1 cells 1537:1541 colon cancer cells 1524:1541 colon cancer cells 1524:1541 By overexpressing the Wnt receptor, FZD-7, in colon cancer cells, we found that FZD-7 receptors expressed N-linked β(1,6) branching, indicating that FZD-7 can be modified by GnT-V. 25274627 2 19 theme CSC 491:493 arg1 regulation 471:480 their regulation 465:480 their regulation of colon CSC 465:493 Because GnT-V levels are also commonly up-regulated in colon cancer, we investigated their regulation of colon CSC and adenoma development. 25274627 2 19 theme CSC 491:493 arg1 development 507:517 adenoma development 499:517 adenoma development 499:517 Because GnT-V levels are also commonly up-regulated in colon cancer, we investigated their regulation of colon CSC and adenoma development. 25274627 4 20 theme GnT-V 1085:1089 arg1 deletion 1073:1080 deletion 1073:1080 deletion of GnT-V 1073:1089 Using Apc(min/+) mice with different GnT-V backgrounds, knock-out of GnT-V had no significant effect on the number of adenoma/mouse, but adenoma size was significantly reduced and accompanied increased survival of Apc(min/+) mice with GnT-V deletion (p < 0.01), suggesting an inhibition in the progression of colon adenoma caused by deletion of GnT-V. 25274627 5 21 theme CSC 1180:1182 arg1 population 1148:1157 the population 1144:1157 the population of colon (intestine) CSC 1144:1182 Decreased expression levels of GnT-V down-regulated the population of colon (intestine) CSC, affecting their ability for self-renewal and tumorigenicity in NOD/SCID mice. 25274627 8 22 theme Wnt 1672:1674 arg1 likely 1728:1733 likely 1728:1733 likely 1728:1733 The aberrant Wnt signaling observed after modulating GnT-V levels is likely to result from altered N-linked β(1,6) branching on FZD-7, thereby affecting Wnt signaling, the compartment of CSC, and tumor progression. 25274627 8 22 theme Wnt 1672:1674 arg1 signaling 1676:1684 The aberrant Wnt signaling 1659:1684 The aberrant Wnt signaling observed after modulating GnT-V levels 1659:1723 The aberrant Wnt signaling observed after modulating GnT-V levels is likely to result from altered N-linked β(1,6) branching on FZD-7, thereby affecting Wnt signaling, the compartment of CSC, and tumor progression. 25274627 4 23 theme colon 1049:1053 arg1 adenoma 1055:1061 colon adenoma 1049:1061 colon adenoma 1049:1061 Using Apc(min/+) mice with different GnT-V backgrounds, knock-out of GnT-V had no significant effect on the number of adenoma/mouse, but adenoma size was significantly reduced and accompanied increased survival of Apc(min/+) mice with GnT-V deletion (p < 0.01), suggesting an inhibition in the progression of colon adenoma caused by deletion of GnT-V. 25274627 4 24 with mice 757:760 arg1 backgrounds 783:793 different GnT-V backgrounds 767:793 different GnT-V backgrounds 767:793 Using Apc(min/+) mice with different GnT-V backgrounds, knock-out of GnT-V had no significant effect on the number of adenoma/mouse, but adenoma size was significantly reduced and accompanied increased survival of Apc(min/+) mice with GnT-V deletion (p < 0.01), suggesting an inhibition in the progression of colon adenoma caused by deletion of GnT-V. 25274627 1 25 theme cells 292:296 arg1 compartment 265:275 the compartment 261:275 the compartment of cancer stem cells (CSC) 261:302 Deletion of GnT-V (MGAT5), which synthesizes N-glycans with β(1,6)-branched glycans, reduced the compartment of cancer stem cells (CSC) in the her-2 mouse model of breast cancer, leading to delay of tumor onset. 25274627 4 26 contain had 815:817 arg1 knock-out 796:804 knock-out 796:804 knock-out of GnT-V 796:813 Using Apc(min/+) mice with different GnT-V backgrounds, knock-out of GnT-V had no significant effect on the number of adenoma/mouse, but adenoma size was significantly reduced and accompanied increased survival of Apc(min/+) mice with GnT-V deletion (p < 0.01), suggesting an inhibition in the progression of colon adenoma caused by deletion of GnT-V. 25274627 4 26 contain had 815:817 arg2 effect 834:839 no significant effect 819:839 no significant effect 819:839 Using Apc(min/+) mice with different GnT-V backgrounds, knock-out of GnT-V had no significant effect on the number of adenoma/mouse, but adenoma size was significantly reduced and accompanied increased survival of Apc(min/+) mice with GnT-V deletion (p < 0.01), suggesting an inhibition in the progression of colon adenoma caused by deletion of GnT-V. 25274627 5 27 theme colon 1162:1166 arg1 CSC 1180:1182 colon (intestine) CSC 1162:1182 colon (intestine) CSC 1162:1182 Decreased expression levels of GnT-V down-regulated the population of colon (intestine) CSC, affecting their ability for self-renewal and tumorigenicity in NOD/SCID mice. 25274627 0 28 theme adenoma 89:95 arg1 progression 97:107 colon adenoma progression 83:107 colon adenoma progression 83:107 Post-translational glycoprotein modifications regulate colon cancer stem cells and colon adenoma progression in Apc(min/+) mice through altered Wnt receptor signaling. 25274627 7 29 theme Wnt 1500:1502 arg1 FZD-7 1514:1518 FZD-7 1514:1518 FZD-7 1514:1518 By overexpressing the Wnt receptor, FZD-7, in colon cancer cells, we found that FZD-7 receptors expressed N-linked β(1,6) branching, indicating that FZD-7 can be modified by GnT-V. 25274627 7 29 theme Wnt 1500:1502 arg1 receptor 1504:1511 the Wnt receptor 1496:1511 the Wnt receptor 1496:1511 By overexpressing the Wnt receptor, FZD-7, in colon cancer cells, we found that FZD-7 receptors expressed N-linked β(1,6) branching, indicating that FZD-7 can be modified by GnT-V. 25274627 4 30 theme adenoma 877:883 arg1 size 885:888 adenoma size 877:888 adenoma size 877:888 Using Apc(min/+) mice with different GnT-V backgrounds, knock-out of GnT-V had no significant effect on the number of adenoma/mouse, but adenoma size was significantly reduced and accompanied increased survival of Apc(min/+) mice with GnT-V deletion (p < 0.01), suggesting an inhibition in the progression of colon adenoma caused by deletion of GnT-V. 25274627 5 31 theme intestine 1169:1177 arg1 CSC 1180:1182 colon (intestine) CSC 1162:1182 colon (intestine) CSC 1162:1182 Decreased expression levels of GnT-V down-regulated the population of colon (intestine) CSC, affecting their ability for self-renewal and tumorigenicity in NOD/SCID mice. 25274627 8 32 theme tumor 1855:1859 arg1 progression 1861:1871 tumor progression 1855:1871 tumor progression 1855:1871 The aberrant Wnt signaling observed after modulating GnT-V levels is likely to result from altered N-linked β(1,6) branching on FZD-7, thereby affecting Wnt signaling, the compartment of CSC, and tumor progression. 25274627 1 33 theme her-2 311:315 arg1 model 323:327 the her-2 mouse model 307:327 the her-2 mouse model of breast cancer 307:344 Deletion of GnT-V (MGAT5), which synthesizes N-glycans with β(1,6)-branched glycans, reduced the compartment of cancer stem cells (CSC) in the her-2 mouse model of breast cancer, leading to delay of tumor onset. 25274627 7 34 theme β 1593:1593 arg1 branching 1600:1608 N-linked β(1,6) branching 1584:1608 N-linked β(1,6) branching 1584:1608 By overexpressing the Wnt receptor, FZD-7, in colon cancer cells, we found that FZD-7 receptors expressed N-linked β(1,6) branching, indicating that FZD-7 can be modified by GnT-V. 25274627 5 35 theme NOD/SCID 1248:1255 arg1 mice 1257:1260 NOD/SCID mice 1248:1260 NOD/SCID mice 1248:1260 Decreased expression levels of GnT-V down-regulated the population of colon (intestine) CSC, affecting their ability for self-renewal and tumorigenicity in NOD/SCID mice. 25274627 6 36 theme genes 1348:1352 arg1 expression 1323:1332 expression 1323:1332 expression of Wnt target genes 1323:1352 Furthermore, altered nuclear translocation of β-catenin and expression of Wnt target genes were positively associated with expression levels of GnT-V, indicating the regulation of canonical Wnt/β-catenin signaling. 25274627 6 36 theme genes 1348:1352 arg1 translocation 1292:1304 altered nuclear translocation 1276:1304 altered nuclear translocation of β-catenin 1276:1317 Furthermore, altered nuclear translocation of β-catenin and expression of Wnt target genes were positively associated with expression levels of GnT-V, indicating the regulation of canonical Wnt/β-catenin signaling. 25274627 4 37 theme mice 965:968 arg1 survival 942:949 increased survival 932:949 increased survival of Apc(min/+) mice 932:968 Using Apc(min/+) mice with different GnT-V backgrounds, knock-out of GnT-V had no significant effect on the number of adenoma/mouse, but adenoma size was significantly reduced and accompanied increased survival of Apc(min/+) mice with GnT-V deletion (p < 0.01), suggesting an inhibition in the progression of colon adenoma caused by deletion of GnT-V. 25274627 6 38 theme Wnt 1337:1339 arg1 genes 1348:1352 Wnt target genes 1337:1352 Wnt target genes 1337:1352 Furthermore, altered nuclear translocation of β-catenin and expression of Wnt target genes were positively associated with expression levels of GnT-V, indicating the regulation of canonical Wnt/β-catenin signaling. 25274627 7 39 theme FZD-7 1558:1562 arg1 receptors 1564:1572 FZD-7 receptors 1558:1572 FZD-7 receptors 1558:1572 By overexpressing the Wnt receptor, FZD-7, in colon cancer cells, we found that FZD-7 receptors expressed N-linked β(1,6) branching, indicating that FZD-7 can be modified by GnT-V. 25274627 0 40 theme colon 55:59 arg1 cells 73:77 colon cancer stem cells 55:77 colon cancer stem cells 55:77 Post-translational glycoprotein modifications regulate colon cancer stem cells and colon adenoma progression in Apc(min/+) mice through altered Wnt receptor signaling. 25274627 0 41 gly glycoprotein 19:30 arg1 glycoprotein 19:30 Post-translational glycoprotein modifications 0:44 Post-translational glycoprotein modifications 0:44 Post-translational glycoprotein modifications regulate colon cancer stem cells and colon adenoma progression in Apc(min/+) mice through altered Wnt receptor signaling. 25274627 2 42 theme GnT-V 388:392 arg1 levels 394:399 GnT-V levels 388:399 GnT-V levels 388:399 Because GnT-V levels are also commonly up-regulated in colon cancer, we investigated their regulation of colon CSC and adenoma development. 25274627 4 43 theme different 767:775 arg1 backgrounds 783:793 different GnT-V backgrounds 767:793 different GnT-V backgrounds 767:793 Using Apc(min/+) mice with different GnT-V backgrounds, knock-out of GnT-V had no significant effect on the number of adenoma/mouse, but adenoma size was significantly reduced and accompanied increased survival of Apc(min/+) mice with GnT-V deletion (p < 0.01), suggesting an inhibition in the progression of colon adenoma caused by deletion of GnT-V. 25274627 0 44 theme stem 68:71 arg1 cells 73:77 colon cancer stem cells 55:77 colon cancer stem cells 55:77 Post-translational glycoprotein modifications regulate colon cancer stem cells and colon adenoma progression in Apc(min/+) mice through altered Wnt receptor signaling. 25274627 1 45 theme cancer 280:285 arg1 CSC 299:301 CSC 299:301 CSC 299:301 Deletion of GnT-V (MGAT5), which synthesizes N-glycans with β(1,6)-branched glycans, reduced the compartment of cancer stem cells (CSC) in the her-2 mouse model of breast cancer, leading to delay of tumor onset. 25274627 1 45 theme cancer 280:285 arg1 cells 292:296 cancer stem cells 280:296 cancer stem cells (CSC) 280:302 Deletion of GnT-V (MGAT5), which synthesizes N-glycans with β(1,6)-branched glycans, reduced the compartment of cancer stem cells (CSC) in the her-2 mouse model of breast cancer, leading to delay of tumor onset. 25274627 4 46 theme Apc 746:748 arg1 mice 757:760 Apc(min/+) mice 746:760 Apc(min/+) mice with different GnT-V backgrounds 746:793 Using Apc(min/+) mice with different GnT-V backgrounds, knock-out of GnT-V had no significant effect on the number of adenoma/mouse, but adenoma size was significantly reduced and accompanied increased survival of Apc(min/+) mice with GnT-V deletion (p < 0.01), suggesting an inhibition in the progression of colon adenoma caused by deletion of GnT-V. 25274627 6 47 theme GnT-V 1407:1411 arg1 levels 1397:1402 expression levels 1386:1402 expression levels of GnT-V 1386:1411 Furthermore, altered nuclear translocation of β-catenin and expression of Wnt target genes were positively associated with expression levels of GnT-V, indicating the regulation of canonical Wnt/β-catenin signaling. 25274627 5 48 theme GnT-V 1123:1127 arg1 levels 1113:1118 Decreased expression levels 1092:1118 Decreased expression levels of GnT-V 1092:1127 Decreased expression levels of GnT-V down-regulated the population of colon (intestine) CSC, affecting their ability for self-renewal and tumorigenicity in NOD/SCID mice. 25274627 3 49 theme tumor 604:608 arg1 cells 610:614 colon tumor cells 598:614 colon tumor cells 598:614 Anchorage-independent cell growth and tumor formation induced by injection of colon tumor cells into NOD/SCID mice were positively associated with GnT-V levels, indicating regulation of proliferation and tumorigenicity. 25274627 4 50 theme Apc 954:956 arg1 mice 965:968 Apc(min/+) mice 954:968 Apc(min/+) mice 954:968 Using Apc(min/+) mice with different GnT-V backgrounds, knock-out of GnT-V had no significant effect on the number of adenoma/mouse, but adenoma size was significantly reduced and accompanied increased survival of Apc(min/+) mice with GnT-V deletion (p < 0.01), suggesting an inhibition in the progression of colon adenoma caused by deletion of GnT-V. 25274627 4 51 theme GnT-V 975:979 arg1 deletion 981:988 GnT-V deletion 975:988 GnT-V deletion (p < 0.01) 975:999 Using Apc(min/+) mice with different GnT-V backgrounds, knock-out of GnT-V had no significant effect on the number of adenoma/mouse, but adenoma size was significantly reduced and accompanied increased survival of Apc(min/+) mice with GnT-V deletion (p < 0.01), suggesting an inhibition in the progression of colon adenoma caused by deletion of GnT-V. 25274627 4 51 theme GnT-V 975:979 arg1 < 993:993 p < 0.01 991:998 p < 0.01 991:998 Using Apc(min/+) mice with different GnT-V backgrounds, knock-out of GnT-V had no significant effect on the number of adenoma/mouse, but adenoma size was significantly reduced and accompanied increased survival of Apc(min/+) mice with GnT-V deletion (p < 0.01), suggesting an inhibition in the progression of colon adenoma caused by deletion of GnT-V. 25274627 8 52 theme CSC 1846:1848 arg1 signaling 1816:1824 Wnt signaling 1812:1824 Wnt signaling 1812:1824 The aberrant Wnt signaling observed after modulating GnT-V levels is likely to result from altered N-linked β(1,6) branching on FZD-7, thereby affecting Wnt signaling, the compartment of CSC, and tumor progression. 25274627 8 52 theme CSC 1846:1848 arg1 compartment 1831:1841 the compartment 1827:1841 the compartment of CSC 1827:1848 The aberrant Wnt signaling observed after modulating GnT-V levels is likely to result from altered N-linked β(1,6) branching on FZD-7, thereby affecting Wnt signaling, the compartment of CSC, and tumor progression. 25274627 8 52 theme CSC 1846:1848 arg1 progression 1861:1871 tumor progression 1855:1871 tumor progression 1855:1871 The aberrant Wnt signaling observed after modulating GnT-V levels is likely to result from altered N-linked β(1,6) branching on FZD-7, thereby affecting Wnt signaling, the compartment of CSC, and tumor progression. 25274627 8 53 theme altered 1750:1756 arg1 1,6 1769:1771 1,6 1769:1771 1,6 1769:1771 The aberrant Wnt signaling observed after modulating GnT-V levels is likely to result from altered N-linked β(1,6) branching on FZD-7, thereby affecting Wnt signaling, the compartment of CSC, and tumor progression. 25274627 8 53 theme altered 1750:1756 arg1 β 1767:1767 altered N-linked β 1750:1767 altered N-linked β(1,6) branching on FZD-7 1750:1791 The aberrant Wnt signaling observed after modulating GnT-V levels is likely to result from altered N-linked β(1,6) branching on FZD-7, thereby affecting Wnt signaling, the compartment of CSC, and tumor progression. 25274627 5 54 theme Decreased 1092:1100 arg1 levels 1113:1118 Decreased expression levels 1092:1118 Decreased expression levels of GnT-V 1092:1127 Decreased expression levels of GnT-V down-regulated the population of colon (intestine) CSC, affecting their ability for self-renewal and tumorigenicity in NOD/SCID mice. 25274627 1 55 theme tumor 367:371 arg1 onset 373:377 tumor onset 367:377 tumor onset 367:377 Deletion of GnT-V (MGAT5), which synthesizes N-glycans with β(1,6)-branched glycans, reduced the compartment of cancer stem cells (CSC) in the her-2 mouse model of breast cancer, leading to delay of tumor onset. 25274627 6 56 theme signaling 1467:1475 arg1 regulation 1429:1438 the regulation 1425:1438 the regulation of canonical Wnt/β-catenin signaling 1425:1475 Furthermore, altered nuclear translocation of β-catenin and expression of Wnt target genes were positively associated with expression levels of GnT-V, indicating the regulation of canonical Wnt/β-catenin signaling. 25274627 6 57 theme β-catenin 1309:1317 arg1 expression 1323:1332 expression 1323:1332 expression of Wnt target genes 1323:1352 Furthermore, altered nuclear translocation of β-catenin and expression of Wnt target genes were positively associated with expression levels of GnT-V, indicating the regulation of canonical Wnt/β-catenin signaling. 25274627 6 57 theme β-catenin 1309:1317 arg1 translocation 1292:1304 altered nuclear translocation 1276:1304 altered nuclear translocation of β-catenin 1276:1317 Furthermore, altered nuclear translocation of β-catenin and expression of Wnt target genes were positively associated with expression levels of GnT-V, indicating the regulation of canonical Wnt/β-catenin signaling. 25274627 4 58 theme GnT-V 777:781 arg1 backgrounds 783:793 different GnT-V backgrounds 767:793 different GnT-V backgrounds 767:793 Using Apc(min/+) mice with different GnT-V backgrounds, knock-out of GnT-V had no significant effect on the number of adenoma/mouse, but adenoma size was significantly reduced and accompanied increased survival of Apc(min/+) mice with GnT-V deletion (p < 0.01), suggesting an inhibition in the progression of colon adenoma caused by deletion of GnT-V. 25274627 6 59 theme altered 1276:1282 arg1 translocation 1292:1304 altered nuclear translocation 1276:1304 altered nuclear translocation of β-catenin 1276:1317 Furthermore, altered nuclear translocation of β-catenin and expression of Wnt target genes were positively associated with expression levels of GnT-V, indicating the regulation of canonical Wnt/β-catenin signaling. 25274627 6 60 theme canonical 1443:1451 arg1 signaling 1467:1475 canonical Wnt/β-catenin signaling 1443:1475 canonical Wnt/β-catenin signaling 1443:1475 Furthermore, altered nuclear translocation of β-catenin and expression of Wnt target genes were positively associated with expression levels of GnT-V, indicating the regulation of canonical Wnt/β-catenin signaling. 25274627 1 61 theme GnT-V 180:184 arg1 Deletion 168:175 Deletion 168:175 Deletion 168:175 Deletion of GnT-V (MGAT5), which synthesizes N-glycans with β(1,6)-branched glycans, reduced the compartment of cancer stem cells (CSC) in the her-2 mouse model of breast cancer, leading to delay of tumor onset. 25274627 4 62 from inhibition 1016:1025 arg1 progression 1034:1044 the progression 1030:1044 the progression of colon adenoma 1030:1061 Using Apc(min/+) mice with different GnT-V backgrounds, knock-out of GnT-V had no significant effect on the number of adenoma/mouse, but adenoma size was significantly reduced and accompanied increased survival of Apc(min/+) mice with GnT-V deletion (p < 0.01), suggesting an inhibition in the progression of colon adenoma caused by deletion of GnT-V. 25274627 0 63 from progression 97:107 arg1 mice 123:126 Apc(min/+) mice 112:126 Apc(min/+) mice 112:126 Post-translational glycoprotein modifications regulate colon cancer stem cells and colon adenoma progression in Apc(min/+) mice through altered Wnt receptor signaling. 25274627 0 64 theme altered 136:142 arg1 signaling 157:165 altered Wnt receptor signaling 136:165 altered Wnt receptor signaling 136:165 Post-translational glycoprotein modifications regulate colon cancer stem cells and colon adenoma progression in Apc(min/+) mice through altered Wnt receptor signaling. 25274627 3 65 theme Anchorage-independent 520:540 arg1 growth 547:552 Anchorage-independent cell growth 520:552 Anchorage-independent cell growth 520:552 Anchorage-independent cell growth and tumor formation induced by injection of colon tumor cells into NOD/SCID mice were positively associated with GnT-V levels, indicating regulation of proliferation and tumorigenicity. 25274627 7 66 theme cancer 1530:1535 arg1 cells 1537:1541 colon cancer cells 1524:1541 colon cancer cells 1524:1541 By overexpressing the Wnt receptor, FZD-7, in colon cancer cells, we found that FZD-7 receptors expressed N-linked β(1,6) branching, indicating that FZD-7 can be modified by GnT-V. 25274627 4 67 theme adenoma/mouse 858:870 arg1 number 848:853 the number 844:853 the number of adenoma/mouse 844:870 Using Apc(min/+) mice with different GnT-V backgrounds, knock-out of GnT-V had no significant effect on the number of adenoma/mouse, but adenoma size was significantly reduced and accompanied increased survival of Apc(min/+) mice with GnT-V deletion (p < 0.01), suggesting an inhibition in the progression of colon adenoma caused by deletion of GnT-V. 25274627 5 68 from self-renewal 1213:1224 arg1 mice 1257:1260 NOD/SCID mice 1248:1260 NOD/SCID mice 1248:1260 Decreased expression levels of GnT-V down-regulated the population of colon (intestine) CSC, affecting their ability for self-renewal and tumorigenicity in NOD/SCID mice. 25274627 0 69 theme receptor 148:155 arg1 signaling 157:165 altered Wnt receptor signaling 136:165 altered Wnt receptor signaling 136:165 Post-translational glycoprotein modifications regulate colon cancer stem cells and colon adenoma progression in Apc(min/+) mice through altered Wnt receptor signaling. 25274627 1 70 theme cancer 339:344 arg1 model 323:327 the her-2 mouse model 307:327 the her-2 mouse model of breast cancer 307:344 Deletion of GnT-V (MGAT5), which synthesizes N-glycans with β(1,6)-branched glycans, reduced the compartment of cancer stem cells (CSC) in the her-2 mouse model of breast cancer, leading to delay of tumor onset. 25274627 4 71 theme significant 822:832 arg1 effect 834:839 no significant effect 819:839 no significant effect 819:839 Using Apc(min/+) mice with different GnT-V backgrounds, knock-out of GnT-V had no significant effect on the number of adenoma/mouse, but adenoma size was significantly reduced and accompanied increased survival of Apc(min/+) mice with GnT-V deletion (p < 0.01), suggesting an inhibition in the progression of colon adenoma caused by deletion of GnT-V. 25274627 3 72 theme tumor 558:562 arg1 formation 564:572 tumor formation 558:572 tumor formation 558:572 Anchorage-independent cell growth and tumor formation induced by injection of colon tumor cells into NOD/SCID mice were positively associated with GnT-V levels, indicating regulation of proliferation and tumorigenicity. 25274627 8 73 link N-linked 1758:1765 arg1 1,6 1769:1771 1,6 1769:1771 1,6 1769:1771 The aberrant Wnt signaling observed after modulating GnT-V levels is likely to result from altered N-linked β(1,6) branching on FZD-7, thereby affecting Wnt signaling, the compartment of CSC, and tumor progression. 25274627 8 73 link N-linked 1758:1765 arg1 β 1767:1767 altered N-linked β 1750:1767 altered N-linked β(1,6) branching on FZD-7 1750:1791 The aberrant Wnt signaling observed after modulating GnT-V levels is likely to result from altered N-linked β(1,6) branching on FZD-7, thereby affecting Wnt signaling, the compartment of CSC, and tumor progression. 25274627 2 74 theme colon 485:489 arg1 CSC 491:493 colon CSC 485:493 colon CSC 485:493 Because GnT-V levels are also commonly up-regulated in colon cancer, we investigated their regulation of colon CSC and adenoma development. 25274627 4 75 theme adenoma 1055:1061 arg1 progression 1034:1044 the progression 1030:1044 the progression of colon adenoma 1030:1061 Using Apc(min/+) mice with different GnT-V backgrounds, knock-out of GnT-V had no significant effect on the number of adenoma/mouse, but adenoma size was significantly reduced and accompanied increased survival of Apc(min/+) mice with GnT-V deletion (p < 0.01), suggesting an inhibition in the progression of colon adenoma caused by deletion of GnT-V. 25274627 0 76 theme colon 83:87 arg1 progression 97:107 colon adenoma progression 83:107 colon adenoma progression 83:107 Post-translational glycoprotein modifications regulate colon cancer stem cells and colon adenoma progression in Apc(min/+) mice through altered Wnt receptor signaling. 25274627 8 77 theme aberrant 1663:1670 arg1 likely 1728:1733 likely 1728:1733 likely 1728:1733 The aberrant Wnt signaling observed after modulating GnT-V levels is likely to result from altered N-linked β(1,6) branching on FZD-7, thereby affecting Wnt signaling, the compartment of CSC, and tumor progression. 25274627 8 77 theme aberrant 1663:1670 arg1 signaling 1676:1684 The aberrant Wnt signaling 1659:1684 The aberrant Wnt signaling observed after modulating GnT-V levels 1659:1723 The aberrant Wnt signaling observed after modulating GnT-V levels is likely to result from altered N-linked β(1,6) branching on FZD-7, thereby affecting Wnt signaling, the compartment of CSC, and tumor progression. 25274627 6 78 theme nuclear 1284:1290 arg1 translocation 1292:1304 altered nuclear translocation 1276:1304 altered nuclear translocation of β-catenin 1276:1317 Furthermore, altered nuclear translocation of β-catenin and expression of Wnt target genes were positively associated with expression levels of GnT-V, indicating the regulation of canonical Wnt/β-catenin signaling. 25274627 0 79 theme Apc 112:114 arg1 mice 123:126 Apc(min/+) mice 112:126 Apc(min/+) mice 112:126 Post-translational glycoprotein modifications regulate colon cancer stem cells and colon adenoma progression in Apc(min/+) mice through altered Wnt receptor signaling. 25274627 7 80 link N-linked 1584:1591 arg1 1,6 1595:1597 1,6 1595:1597 1,6 1595:1597 By overexpressing the Wnt receptor, FZD-7, in colon cancer cells, we found that FZD-7 receptors expressed N-linked β(1,6) branching, indicating that FZD-7 can be modified by GnT-V. 25274627 7 80 link N-linked 1584:1591 arg1 β 1593:1593 N-linked β 1584:1593 N-linked β(1,6) branching 1584:1608 By overexpressing the Wnt receptor, FZD-7, in colon cancer cells, we found that FZD-7 receptors expressed N-linked β(1,6) branching, indicating that FZD-7 can be modified by GnT-V. 25274627 0 81 from cells 73:77 arg1 mice 123:126 Apc(min/+) mice 112:126 Apc(min/+) mice 112:126 Post-translational glycoprotein modifications regulate colon cancer stem cells and colon adenoma progression in Apc(min/+) mice through altered Wnt receptor signaling. 25274627 8 82 theme GnT-V 1712:1716 arg1 levels 1718:1723 GnT-V levels 1712:1723 GnT-V levels 1712:1723 The aberrant Wnt signaling observed after modulating GnT-V levels is likely to result from altered N-linked β(1,6) branching on FZD-7, thereby affecting Wnt signaling, the compartment of CSC, and tumor progression. 25274627 2 83 theme colon 435:439 arg1 cancer 441:446 colon cancer 435:446 colon cancer 435:446 Because GnT-V levels are also commonly up-regulated in colon cancer, we investigated their regulation of colon CSC and adenoma development. 25274627 0 84 theme glycoprotein 19:30 arg1 modifications 32:44 Post-translational glycoprotein modifications 0:44 Post-translational glycoprotein modifications 0:44 Post-translational glycoprotein modifications regulate colon cancer stem cells and colon adenoma progression in Apc(min/+) mice through altered Wnt receptor signaling. 25274627 1 85 theme mouse 317:321 arg1 model 323:327 the her-2 mouse model 307:327 the her-2 mouse model of breast cancer 307:344 Deletion of GnT-V (MGAT5), which synthesizes N-glycans with β(1,6)-branched glycans, reduced the compartment of cancer stem cells (CSC) in the her-2 mouse model of breast cancer, leading to delay of tumor onset. 25274627 5 86 from mice 1257:1260 arg1 self-renewal 1213:1224 self-renewal 1213:1224 self-renewal 1213:1224 Decreased expression levels of GnT-V down-regulated the population of colon (intestine) CSC, affecting their ability for self-renewal and tumorigenicity in NOD/SCID mice. 25274627 6 87 theme target 1341:1346 arg1 genes 1348:1352 Wnt target genes 1337:1352 Wnt target genes 1337:1352 Furthermore, altered nuclear translocation of β-catenin and expression of Wnt target genes were positively associated with expression levels of GnT-V, indicating the regulation of canonical Wnt/β-catenin signaling. 25274627 7 88 theme N-linked 1584:1591 arg1 1,6 1595:1597 1,6 1595:1597 1,6 1595:1597 By overexpressing the Wnt receptor, FZD-7, in colon cancer cells, we found that FZD-7 receptors expressed N-linked β(1,6) branching, indicating that FZD-7 can be modified by GnT-V. 25274627 7 88 theme N-linked 1584:1591 arg1 β 1593:1593 N-linked β 1584:1593 N-linked β(1,6) branching 1584:1608 By overexpressing the Wnt receptor, FZD-7, in colon cancer cells, we found that FZD-7 receptors expressed N-linked β(1,6) branching, indicating that FZD-7 can be modified by GnT-V. 25274627 0 89 theme cancer 61:66 arg1 cells 73:77 colon cancer stem cells 55:77 colon cancer stem cells 55:77 Post-translational glycoprotein modifications regulate colon cancer stem cells and colon adenoma progression in Apc(min/+) mice through altered Wnt receptor signaling. 25274627 4 90 theme increased 932:940 arg1 survival 942:949 increased survival 932:949 increased survival of Apc(min/+) mice 932:968 Using Apc(min/+) mice with different GnT-V backgrounds, knock-out of GnT-V had no significant effect on the number of adenoma/mouse, but adenoma size was significantly reduced and accompanied increased survival of Apc(min/+) mice with GnT-V deletion (p < 0.01), suggesting an inhibition in the progression of colon adenoma caused by deletion of GnT-V. 25274627 3 91 theme cells 610:614 arg1 injection 585:593 injection 585:593 injection of colon tumor cells into NOD/SCID mice 585:633 Anchorage-independent cell growth and tumor formation induced by injection of colon tumor cells into NOD/SCID mice were positively associated with GnT-V levels, indicating regulation of proliferation and tumorigenicity. 25274627 1 92 theme stem 287:290 arg1 CSC 299:301 CSC 299:301 CSC 299:301 Deletion of GnT-V (MGAT5), which synthesizes N-glycans with β(1,6)-branched glycans, reduced the compartment of cancer stem cells (CSC) in the her-2 mouse model of breast cancer, leading to delay of tumor onset. 25274627 1 92 theme stem 287:290 arg1 cells 292:296 cancer stem cells 280:296 cancer stem cells (CSC) 280:302 Deletion of GnT-V (MGAT5), which synthesizes N-glycans with β(1,6)-branched glycans, reduced the compartment of cancer stem cells (CSC) in the her-2 mouse model of breast cancer, leading to delay of tumor onset. 25274627 4 93 theme p 991:991 arg1 deletion 981:988 GnT-V deletion 975:988 GnT-V deletion (p < 0.01) 975:999 Using Apc(min/+) mice with different GnT-V backgrounds, knock-out of GnT-V had no significant effect on the number of adenoma/mouse, but adenoma size was significantly reduced and accompanied increased survival of Apc(min/+) mice with GnT-V deletion (p < 0.01), suggesting an inhibition in the progression of colon adenoma caused by deletion of GnT-V. 25274627 4 93 theme p 991:991 arg1 < 993:993 p < 0.01 991:998 p < 0.01 991:998 Using Apc(min/+) mice with different GnT-V backgrounds, knock-out of GnT-V had no significant effect on the number of adenoma/mouse, but adenoma size was significantly reduced and accompanied increased survival of Apc(min/+) mice with GnT-V deletion (p < 0.01), suggesting an inhibition in the progression of colon adenoma caused by deletion of GnT-V. 25274627 3 94 theme colon 598:602 arg1 cells 610:614 colon tumor cells 598:614 colon tumor cells 598:614 Anchorage-independent cell growth and tumor formation induced by injection of colon tumor cells into NOD/SCID mice were positively associated with GnT-V levels, indicating regulation of proliferation and tumorigenicity. 25274627 6 95 theme expression 1386:1395 arg1 levels 1397:1402 expression levels 1386:1402 expression levels of GnT-V 1386:1411 Furthermore, altered nuclear translocation of β-catenin and expression of Wnt target genes were positively associated with expression levels of GnT-V, indicating the regulation of canonical Wnt/β-catenin signaling. 24035784 5 0 theme study 816:820 arg1 aim 797:799 The aim 793:799 The aim of the current study 793:820 The aim of the current study was to determine the implications of the O-GlcNAc modification on T cell apoptosis. 24035784 5 1 from implications 843:854 arg1 apoptosis 895:903 T cell apoptosis 888:903 T cell apoptosis 888:903 The aim of the current study was to determine the implications of the O-GlcNAc modification on T cell apoptosis. 24035784 12 2 theme O-GlcNAcylated 1666:1679 arg1 DFF45 1681:1685 O-GlcNAcylated DFF45 1666:1685 O-GlcNAcylated DFF45 1666:1685 O-GlcNAcylated DFF45 appeared to be more resistant to caspase cleavage during apoptosis. 24035784 13 3 theme O-GlcNAc 1798:1805 arg1 modification 1807:1818 the O-GlcNAc modification 1794:1818 the O-GlcNAc modification on DFF45 1794:1827 Our results suggest that a decrease in the O-GlcNAc modification on DFF45 occurs before its cleavage by caspase. 24035784 0 4 theme apoptosis 71:79 arg1 regulation 49:58 the regulation 45:58 the regulation of nuclear apoptosis in T cells 45:90 Implications of the O-GlcNAc modification in the regulation of nuclear apoptosis in T cells. 24035784 10 5 theme significant 1497:1507 arg1 reduction 1509:1517 a significant reduction 1495:1517 a significant reduction in DNA fragmentation 1495:1538 RESULTS HPB-ALL cells treated with PUGNAc displayed a significant reduction in DNA fragmentation after TBT-induced apoptosis. 24035784 10 6 theme HPB-ALL 1451:1457 arg1 cells 1459:1463 RESULTS HPB-ALL cells 1443:1463 RESULTS HPB-ALL cells treated with PUGNAc 1443:1483 RESULTS HPB-ALL cells treated with PUGNAc displayed a significant reduction in DNA fragmentation after TBT-induced apoptosis. 24035784 1 7 theme nutrient-/stress-sensitive 151:176 arg1 modification 197:208 a nutrient-/stress-sensitive post-translational modification 149:208 a nutrient-/stress-sensitive post-translational modification that affects nucleocytoplasmic proteins 149:248 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) is a nutrient-/stress-sensitive post-translational modification that affects nucleocytoplasmic proteins. 24035784 1 7 theme nutrient-/stress-sensitive 151:176 arg1 β-N-acetylglucosamine 113:133 BACKGROUND O-linked β-N-acetylglucosamine 93:133 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) 93:144 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) is a nutrient-/stress-sensitive post-translational modification that affects nucleocytoplasmic proteins. 24035784 9 8 theme O-GlcNAcylated 1283:1296 arg1 proteins 1298:1305 O-GlcNAcylated proteins 1283:1305 O-GlcNAcylated proteins 1283:1305 O-GlcNAcylated proteins were detected by immunoblot using a specific antibody (ctd110.6) and were precipitated using succinylated wheat germ agglutinin (sWGA). 24035784 0 9 from Implications 0:11 arg1 regulation 49:58 the regulation 45:58 the regulation of nuclear apoptosis in T cells 45:90 Implications of the O-GlcNAc modification in the regulation of nuclear apoptosis in T cells. 24035784 6 10 theme Human 914:918 arg1 cells 944:948 Human T lymphoblastic HPB-ALL cells 914:948 METHODS Human T lymphoblastic HPB-ALL cells 906:948 METHODS Human T lymphoblastic HPB-ALL cells were treated with the OGA inhibitor O-(2-acetamido-2-deoxy-d-glucopyranosylidene) amino-N-phenylcarbamate (PUGNAc), or with glucosamine (GlcN), to increase O-GlcNAcylation. 24035784 4 11 theme ventricular 718:728 arg1 myocytes 730:737 primary neonatal rat ventricular myocytes 697:737 primary neonatal rat ventricular myocytes 697:737 The effects of O-GlcNAcylation on apoptosis appear to be cell-dependent, as elevated levels played a protective role in primary neonatal rat ventricular myocytes but had a cytotoxic effect in rat pancreatic β-cells. 24035784 4 12 theme elevated 653:660 arg1 levels 662:667 elevated levels 653:667 elevated levels played a protective role in primary neonatal rat ventricular myocytes but had a cytotoxic effect in rat pancreatic β-cells 653:790 The effects of O-GlcNAcylation on apoptosis appear to be cell-dependent, as elevated levels played a protective role in primary neonatal rat ventricular myocytes but had a cytotoxic effect in rat pancreatic β-cells. 24035784 0 13 theme T 84:84 arg1 cells 86:90 T cells 84:90 T cells 84:90 Implications of the O-GlcNAc modification in the regulation of nuclear apoptosis in T cells. 24035784 0 14 from regulation 49:58 arg1 cells 86:90 T cells 84:90 T cells 84:90 Implications of the O-GlcNAc modification in the regulation of nuclear apoptosis in T cells. 24035784 14 15 theme DFF 2010:2012 arg1 activation 1996:2005 the accidental activation 1981:2005 the accidental activation of DFF 1981:2012 GENERAL SIGNIFICANCE Our results indicate that the O-GlcNAcylation of DFF45 may represent a mechanism to control the accidental activation of DFF. 24035784 2 16 theme O-GlcNAc 328:335 arg1 addition 316:323 the addition 312:323 the addition of O-GlcNAc 312:335 The enzyme O-N-acetylglucosamine transferase (OGT) catalyzes the addition of O-GlcNAc, whereas O-N-acetylglucosaminidase (OGA) removes it. 24035784 5 17 theme cell 890:893 arg1 apoptosis 895:903 T cell apoptosis 888:903 T cell apoptosis 888:903 The aim of the current study was to determine the implications of the O-GlcNAc modification on T cell apoptosis. 24035784 4 18 theme cytotoxic 749:757 arg1 effect 759:764 a cytotoxic effect 747:764 a cytotoxic effect 747:764 The effects of O-GlcNAcylation on apoptosis appear to be cell-dependent, as elevated levels played a protective role in primary neonatal rat ventricular myocytes but had a cytotoxic effect in rat pancreatic β-cells. 24035784 3 19 theme cell 547:550 arg1 signaling 552:560 cell signaling 547:560 cell signaling 547:560 O-GlcNAcylation plays a role in fundamental regulatory mechanisms through the modification of proteins involved in cell division, metabolism, transcription, cell signaling and apoptosis. 24035784 8 20 theme cycle 1222:1226 arg1 analysis 1228:1235 cell cycle analysis 1217:1235 cell cycle analysis 1217:1235 DNA fragmentation was observed by cell cycle analysis and corresponded to the sub G0/G1 population. 24035784 14 21 theme accidental 1985:1994 arg1 activation 1996:2005 the accidental activation 1981:2005 the accidental activation of DFF 1981:2012 GENERAL SIGNIFICANCE Our results indicate that the O-GlcNAcylation of DFF45 may represent a mechanism to control the accidental activation of DFF. 24035784 12 22 theme caspase 1720:1726 arg1 cleavage 1728:1735 caspase cleavage 1720:1735 caspase cleavage during apoptosis 1720:1752 O-GlcNAcylated DFF45 appeared to be more resistant to caspase cleavage during apoptosis. 24035784 1 23 theme post-translational 178:195 arg1 modification 197:208 a nutrient-/stress-sensitive post-translational modification 149:208 a nutrient-/stress-sensitive post-translational modification that affects nucleocytoplasmic proteins 149:248 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) is a nutrient-/stress-sensitive post-translational modification that affects nucleocytoplasmic proteins. 24035784 1 23 theme post-translational 178:195 arg1 β-N-acetylglucosamine 113:133 BACKGROUND O-linked β-N-acetylglucosamine 93:133 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) 93:144 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) is a nutrient-/stress-sensitive post-translational modification that affects nucleocytoplasmic proteins. 24035784 8 24 theme G0/G1 1265:1269 arg1 population 1271:1280 the sub G0/G1 population 1257:1280 the sub G0/G1 population 1257:1280 DNA fragmentation was observed by cell cycle analysis and corresponded to the sub G0/G1 population. 24035784 6 25 theme HPB-ALL 936:942 arg1 cells 944:948 Human T lymphoblastic HPB-ALL cells 914:948 METHODS Human T lymphoblastic HPB-ALL cells 906:948 METHODS Human T lymphoblastic HPB-ALL cells were treated with the OGA inhibitor O-(2-acetamido-2-deoxy-d-glucopyranosylidene) amino-N-phenylcarbamate (PUGNAc), or with glucosamine (GlcN), to increase O-GlcNAcylation. 24035784 3 26 theme cell 505:508 arg1 division 510:517 cell division 505:517 cell division 505:517 O-GlcNAcylation plays a role in fundamental regulatory mechanisms through the modification of proteins involved in cell division, metabolism, transcription, cell signaling and apoptosis. 24035784 3 27 theme regulatory 434:443 arg1 mechanisms 445:454 fundamental regulatory mechanisms 422:454 fundamental regulatory mechanisms 422:454 O-GlcNAcylation plays a role in fundamental regulatory mechanisms through the modification of proteins involved in cell division, metabolism, transcription, cell signaling and apoptosis. 24035784 6 28 theme lymphoblastic 922:934 arg1 cells 944:948 Human T lymphoblastic HPB-ALL cells 914:948 METHODS Human T lymphoblastic HPB-ALL cells 906:948 METHODS Human T lymphoblastic HPB-ALL cells were treated with the OGA inhibitor O-(2-acetamido-2-deoxy-d-glucopyranosylidene) amino-N-phenylcarbamate (PUGNAc), or with glucosamine (GlcN), to increase O-GlcNAcylation. 24035784 10 29 theme DNA 1522:1524 arg1 fragmentation 1526:1538 DNA fragmentation 1522:1538 DNA fragmentation 1522:1538 RESULTS HPB-ALL cells treated with PUGNAc displayed a significant reduction in DNA fragmentation after TBT-induced apoptosis. 24035784 8 30 theme DNA 1183:1185 arg1 fragmentation 1187:1199 DNA fragmentation 1183:1199 DNA fragmentation 1183:1199 DNA fragmentation was observed by cell cycle analysis and corresponded to the sub G0/G1 population. 24035784 3 31 theme proteins 484:491 arg1 modification 468:479 the modification 464:479 the modification of proteins involved in cell division, metabolism, transcription, cell signaling and apoptosis 464:574 O-GlcNAcylation plays a role in fundamental regulatory mechanisms through the modification of proteins involved in cell division, metabolism, transcription, cell signaling and apoptosis. 24035784 6 32 theme inhibitor 976:984 arg1 PUGNAc 1057:1062 the OGA inhibitor O-(2-acetamido-2-deoxy-d-glucopyranosylidene) amino-N-phenylcarbamate (PUGNAc) 968:1063 the OGA inhibitor O-(2-acetamido-2-deoxy-d-glucopyranosylidene) amino-N-phenylcarbamate (PUGNAc) 968:1063 METHODS Human T lymphoblastic HPB-ALL cells were treated with the OGA inhibitor O-(2-acetamido-2-deoxy-d-glucopyranosylidene) amino-N-phenylcarbamate (PUGNAc), or with glucosamine (GlcN), to increase O-GlcNAcylation. 24035784 2 33 dep catalyzes 302:310 arg1 whereas 338:344 whereas 338:344 whereas 338:344 The enzyme O-N-acetylglucosamine transferase (OGT) catalyzes the addition of O-GlcNAc, whereas O-N-acetylglucosaminidase (OGA) removes it. 24035784 0 34 theme O-GlcNAc 20:27 arg1 modification 29:40 the O-GlcNAc modification 16:40 the O-GlcNAc modification 16:40 Implications of the O-GlcNAc modification in the regulation of nuclear apoptosis in T cells. 24035784 8 35 theme cell 1217:1220 arg1 analysis 1228:1235 cell cycle analysis 1217:1235 cell cycle analysis 1217:1235 DNA fragmentation was observed by cell cycle analysis and corresponded to the sub G0/G1 population. 24035784 4 36 theme rat 769:771 arg1 β-cells 784:790 rat pancreatic β-cells 769:790 rat pancreatic β-cells 769:790 The effects of O-GlcNAcylation on apoptosis appear to be cell-dependent, as elevated levels played a protective role in primary neonatal rat ventricular myocytes but had a cytotoxic effect in rat pancreatic β-cells. 24035784 11 37 theme endonuclease 1606:1617 arg1 DFF40 1619:1623 the endonuclease DFF40 1602:1623 the endonuclease DFF40 1602:1623 DFF45, the protein that inhibits the endonuclease DFF40, was identified to be O-GlcNAc modified. 24035784 1 38 theme nucleocytoplasmic 223:239 arg1 proteins 241:248 nucleocytoplasmic proteins 223:248 nucleocytoplasmic proteins 223:248 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) is a nutrient-/stress-sensitive post-translational modification that affects nucleocytoplasmic proteins. 24035784 3 39 theme fundamental 422:432 arg1 mechanisms 445:454 fundamental regulatory mechanisms 422:454 fundamental regulatory mechanisms 422:454 O-GlcNAcylation plays a role in fundamental regulatory mechanisms through the modification of proteins involved in cell division, metabolism, transcription, cell signaling and apoptosis. 24035784 6 40 theme amino-N-phenylcarbamate 1032:1054 arg1 PUGNAc 1057:1062 the OGA inhibitor O-(2-acetamido-2-deoxy-d-glucopyranosylidene) amino-N-phenylcarbamate (PUGNAc) 968:1063 the OGA inhibitor O-(2-acetamido-2-deoxy-d-glucopyranosylidene) amino-N-phenylcarbamate (PUGNAc) 968:1063 METHODS Human T lymphoblastic HPB-ALL cells were treated with the OGA inhibitor O-(2-acetamido-2-deoxy-d-glucopyranosylidene) amino-N-phenylcarbamate (PUGNAc), or with glucosamine (GlcN), to increase O-GlcNAcylation. 24035784 6 41 theme T 920:920 arg1 cells 944:948 Human T lymphoblastic HPB-ALL cells 914:948 METHODS Human T lymphoblastic HPB-ALL cells 906:948 METHODS Human T lymphoblastic HPB-ALL cells were treated with the OGA inhibitor O-(2-acetamido-2-deoxy-d-glucopyranosylidene) amino-N-phenylcarbamate (PUGNAc), or with glucosamine (GlcN), to increase O-GlcNAcylation. 24035784 1 42 theme BACKGROUND 93:102 arg1 O-GlcNAc 136:143 O-GlcNAc 136:143 O-GlcNAc 136:143 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) is a nutrient-/stress-sensitive post-translational modification that affects nucleocytoplasmic proteins. 24035784 1 42 theme BACKGROUND 93:102 arg1 β-N-acetylglucosamine 113:133 BACKGROUND O-linked β-N-acetylglucosamine 93:133 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) 93:144 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) is a nutrient-/stress-sensitive post-translational modification that affects nucleocytoplasmic proteins. 24035784 1 42 theme BACKGROUND 93:102 arg1 modification 197:208 a nutrient-/stress-sensitive post-translational modification 149:208 a nutrient-/stress-sensitive post-translational modification that affects nucleocytoplasmic proteins 149:248 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) is a nutrient-/stress-sensitive post-translational modification that affects nucleocytoplasmic proteins. 24035784 5 43 theme T 888:888 arg1 apoptosis 895:903 T cell apoptosis 888:903 T cell apoptosis 888:903 The aim of the current study was to determine the implications of the O-GlcNAc modification on T cell apoptosis. 24035784 8 44 theme sub 1261:1263 arg1 population 1271:1280 the sub G0/G1 population 1257:1280 the sub G0/G1 population 1257:1280 DNA fragmentation was observed by cell cycle analysis and corresponded to the sub G0/G1 population. 24035784 9 45 theme wheat 1413:1417 arg1 agglutinin 1424:1433 succinylated wheat germ agglutinin 1400:1433 succinylated wheat germ agglutinin (sWGA) 1400:1440 O-GlcNAcylated proteins were detected by immunoblot using a specific antibody (ctd110.6) and were precipitated using succinylated wheat germ agglutinin (sWGA). 24035784 9 45 theme wheat 1413:1417 arg1 sWGA 1436:1439 sWGA 1436:1439 sWGA 1436:1439 O-GlcNAcylated proteins were detected by immunoblot using a specific antibody (ctd110.6) and were precipitated using succinylated wheat germ agglutinin (sWGA). 24035784 0 46 from apoptosis 71:79 arg1 cells 86:90 T cells 84:90 T cells 84:90 Implications of the O-GlcNAc modification in the regulation of nuclear apoptosis in T cells. 24035784 4 47 theme neonatal 705:712 arg1 myocytes 730:737 primary neonatal rat ventricular myocytes 697:737 primary neonatal rat ventricular myocytes 697:737 The effects of O-GlcNAcylation on apoptosis appear to be cell-dependent, as elevated levels played a protective role in primary neonatal rat ventricular myocytes but had a cytotoxic effect in rat pancreatic β-cells. 24035784 0 48 theme modification 29:40 arg1 Implications 0:11 Implications 0:11 Implications of the O-GlcNAc modification in the regulation of nuclear apoptosis in T cells 0:90 Implications of the O-GlcNAc modification in the regulation of nuclear apoptosis in T cells. 24035784 6 49 theme 2-acetamido-2-deoxy-d-glucopyranosylidene 989:1029 arg1 PUGNAc 1057:1062 the OGA inhibitor O-(2-acetamido-2-deoxy-d-glucopyranosylidene) amino-N-phenylcarbamate (PUGNAc) 968:1063 the OGA inhibitor O-(2-acetamido-2-deoxy-d-glucopyranosylidene) amino-N-phenylcarbamate (PUGNAc) 968:1063 METHODS Human T lymphoblastic HPB-ALL cells were treated with the OGA inhibitor O-(2-acetamido-2-deoxy-d-glucopyranosylidene) amino-N-phenylcarbamate (PUGNAc), or with glucosamine (GlcN), to increase O-GlcNAcylation. 24035784 10 50 theme TBT-induced 1546:1556 arg1 apoptosis 1558:1566 TBT-induced apoptosis 1546:1566 TBT-induced apoptosis 1546:1566 RESULTS HPB-ALL cells treated with PUGNAc displayed a significant reduction in DNA fragmentation after TBT-induced apoptosis. 24035784 13 51 from decrease 1782:1789 arg1 modification 1807:1818 the O-GlcNAc modification 1794:1818 the O-GlcNAc modification on DFF45 1794:1827 Our results suggest that a decrease in the O-GlcNAc modification on DFF45 occurs before its cleavage by caspase. 24035784 13 51 from decrease 1782:1789 arg1 DFF45 1823:1827 DFF45 1823:1827 DFF45 1823:1827 Our results suggest that a decrease in the O-GlcNAc modification on DFF45 occurs before its cleavage by caspase. 24035784 5 52 theme O-GlcNAc 863:870 arg1 modification 872:883 the O-GlcNAc modification 859:883 the O-GlcNAc modification 859:883 The aim of the current study was to determine the implications of the O-GlcNAc modification on T cell apoptosis. 24035784 4 53 theme primary 697:703 arg1 myocytes 730:737 primary neonatal rat ventricular myocytes 697:737 primary neonatal rat ventricular myocytes 697:737 The effects of O-GlcNAcylation on apoptosis appear to be cell-dependent, as elevated levels played a protective role in primary neonatal rat ventricular myocytes but had a cytotoxic effect in rat pancreatic β-cells. 24035784 6 54 dep METHODS 906:912 arg1 cells 944:948 Human T lymphoblastic HPB-ALL cells 914:948 METHODS Human T lymphoblastic HPB-ALL cells 906:948 METHODS Human T lymphoblastic HPB-ALL cells were treated with the OGA inhibitor O-(2-acetamido-2-deoxy-d-glucopyranosylidene) amino-N-phenylcarbamate (PUGNAc), or with glucosamine (GlcN), to increase O-GlcNAcylation. 24035784 10 55 theme RESULTS 1443:1449 arg1 cells 1459:1463 RESULTS HPB-ALL cells 1443:1463 RESULTS HPB-ALL cells treated with PUGNAc 1443:1483 RESULTS HPB-ALL cells treated with PUGNAc displayed a significant reduction in DNA fragmentation after TBT-induced apoptosis. 24035784 2 56 theme O-N-acetylglucosamine 262:282 arg1 transferase 284:294 The enzyme O-N-acetylglucosamine transferase 251:294 The enzyme O-N-acetylglucosamine transferase (OGT) 251:300 The enzyme O-N-acetylglucosamine transferase (OGT) catalyzes the addition of O-GlcNAc, whereas O-N-acetylglucosaminidase (OGA) removes it. 24035784 2 56 theme O-N-acetylglucosamine 262:282 arg1 OGT 297:299 OGT 297:299 OGT 297:299 The enzyme O-N-acetylglucosamine transferase (OGT) catalyzes the addition of O-GlcNAc, whereas O-N-acetylglucosaminidase (OGA) removes it. 24035784 13 57 from DFF45 1823:1827 arg1 decrease 1782:1789 a decrease 1780:1789 a decrease in the O-GlcNAc modification on DFF45 1780:1827 Our results suggest that a decrease in the O-GlcNAc modification on DFF45 occurs before its cleavage by caspase. 24035784 1 58 theme O-linked 104:111 arg1 O-GlcNAc 136:143 O-GlcNAc 136:143 O-GlcNAc 136:143 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) is a nutrient-/stress-sensitive post-translational modification that affects nucleocytoplasmic proteins. 24035784 1 58 theme O-linked 104:111 arg1 β-N-acetylglucosamine 113:133 BACKGROUND O-linked β-N-acetylglucosamine 93:133 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) 93:144 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) is a nutrient-/stress-sensitive post-translational modification that affects nucleocytoplasmic proteins. 24035784 1 58 theme O-linked 104:111 arg1 modification 197:208 a nutrient-/stress-sensitive post-translational modification 149:208 a nutrient-/stress-sensitive post-translational modification that affects nucleocytoplasmic proteins 149:248 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) is a nutrient-/stress-sensitive post-translational modification that affects nucleocytoplasmic proteins. 24035784 4 59 from effects 581:587 arg1 apoptosis 611:619 apoptosis 611:619 apoptosis 611:619 The effects of O-GlcNAcylation on apoptosis appear to be cell-dependent, as elevated levels played a protective role in primary neonatal rat ventricular myocytes but had a cytotoxic effect in rat pancreatic β-cells. 24035784 6 60 theme O- 986:987 arg1 PUGNAc 1057:1062 the OGA inhibitor O-(2-acetamido-2-deoxy-d-glucopyranosylidene) amino-N-phenylcarbamate (PUGNAc) 968:1063 the OGA inhibitor O-(2-acetamido-2-deoxy-d-glucopyranosylidene) amino-N-phenylcarbamate (PUGNAc) 968:1063 METHODS Human T lymphoblastic HPB-ALL cells were treated with the OGA inhibitor O-(2-acetamido-2-deoxy-d-glucopyranosylidene) amino-N-phenylcarbamate (PUGNAc), or with glucosamine (GlcN), to increase O-GlcNAcylation. 24035784 13 61 from modification 1807:1818 arg1 DFF45 1823:1827 DFF45 1823:1827 DFF45 1823:1827 Our results suggest that a decrease in the O-GlcNAc modification on DFF45 occurs before its cleavage by caspase. 24035784 2 62 theme enzyme 255:260 arg1 transferase 284:294 The enzyme O-N-acetylglucosamine transferase 251:294 The enzyme O-N-acetylglucosamine transferase (OGT) 251:300 The enzyme O-N-acetylglucosamine transferase (OGT) catalyzes the addition of O-GlcNAc, whereas O-N-acetylglucosaminidase (OGA) removes it. 24035784 2 62 theme enzyme 255:260 arg1 OGT 297:299 OGT 297:299 OGT 297:299 The enzyme O-N-acetylglucosamine transferase (OGT) catalyzes the addition of O-GlcNAc, whereas O-N-acetylglucosaminidase (OGA) removes it. 24035784 9 63 theme specific 1343:1350 arg1 antibody 1352:1359 a specific antibody 1341:1359 a specific antibody (ctd110.6) 1341:1370 O-GlcNAcylated proteins were detected by immunoblot using a specific antibody (ctd110.6) and were precipitated using succinylated wheat germ agglutinin (sWGA). 24035784 9 63 theme specific 1343:1350 arg1 ctd110.6 1362:1369 ctd110.6 1362:1369 ctd110.6 1362:1369 O-GlcNAcylated proteins were detected by immunoblot using a specific antibody (ctd110.6) and were precipitated using succinylated wheat germ agglutinin (sWGA). 24035784 4 64 theme O-GlcNAcylation 592:606 arg1 effects 581:587 The effects 577:587 The effects of O-GlcNAcylation on apoptosis 577:619 The effects of O-GlcNAcylation on apoptosis appear to be cell-dependent, as elevated levels played a protective role in primary neonatal rat ventricular myocytes but had a cytotoxic effect in rat pancreatic β-cells. 24035784 4 64 theme O-GlcNAcylation 592:606 arg1 cell-dependent 634:647 cell-dependent 634:647 cell-dependent 634:647 The effects of O-GlcNAcylation on apoptosis appear to be cell-dependent, as elevated levels played a protective role in primary neonatal rat ventricular myocytes but had a cytotoxic effect in rat pancreatic β-cells. 24035784 1 65 link O-linked 104:111 arg1 O-GlcNAc 136:143 O-GlcNAc 136:143 O-GlcNAc 136:143 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) is a nutrient-/stress-sensitive post-translational modification that affects nucleocytoplasmic proteins. 24035784 1 65 link O-linked 104:111 arg1 β-N-acetylglucosamine 113:133 BACKGROUND O-linked β-N-acetylglucosamine 93:133 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) 93:144 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) is a nutrient-/stress-sensitive post-translational modification that affects nucleocytoplasmic proteins. 24035784 1 65 link O-linked 104:111 arg1 modification 197:208 a nutrient-/stress-sensitive post-translational modification 149:208 a nutrient-/stress-sensitive post-translational modification that affects nucleocytoplasmic proteins 149:248 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) is a nutrient-/stress-sensitive post-translational modification that affects nucleocytoplasmic proteins. 24035784 9 66 theme succinylated 1400:1411 arg1 agglutinin 1424:1433 succinylated wheat germ agglutinin 1400:1433 succinylated wheat germ agglutinin (sWGA) 1400:1440 O-GlcNAcylated proteins were detected by immunoblot using a specific antibody (ctd110.6) and were precipitated using succinylated wheat germ agglutinin (sWGA). 24035784 9 66 theme succinylated 1400:1411 arg1 sWGA 1436:1439 sWGA 1436:1439 sWGA 1436:1439 O-GlcNAcylated proteins were detected by immunoblot using a specific antibody (ctd110.6) and were precipitated using succinylated wheat germ agglutinin (sWGA). 24035784 14 67 theme DFF45 1938:1942 arg1 O-GlcNAcylation 1919:1933 the O-GlcNAcylation 1915:1933 the O-GlcNAcylation of DFF45 1915:1942 GENERAL SIGNIFICANCE Our results indicate that the O-GlcNAcylation of DFF45 may represent a mechanism to control the accidental activation of DFF. 24035784 14 68 theme GENERAL 1868:1874 arg1 results 1893:1899 GENERAL SIGNIFICANCE Our results 1868:1899 GENERAL SIGNIFICANCE Our results 1868:1899 GENERAL SIGNIFICANCE Our results indicate that the O-GlcNAcylation of DFF45 may represent a mechanism to control the accidental activation of DFF. 24035784 0 69 from cells 86:90 arg1 regulation 49:58 the regulation 45:58 the regulation of nuclear apoptosis in T cells 45:90 Implications of the O-GlcNAc modification in the regulation of nuclear apoptosis in T cells. 24035784 4 70 theme pancreatic 773:782 arg1 β-cells 784:790 rat pancreatic β-cells 769:790 rat pancreatic β-cells 769:790 The effects of O-GlcNAcylation on apoptosis appear to be cell-dependent, as elevated levels played a protective role in primary neonatal rat ventricular myocytes but had a cytotoxic effect in rat pancreatic β-cells. 24035784 9 71 theme germ 1419:1422 arg1 agglutinin 1424:1433 succinylated wheat germ agglutinin 1400:1433 succinylated wheat germ agglutinin (sWGA) 1400:1440 O-GlcNAcylated proteins were detected by immunoblot using a specific antibody (ctd110.6) and were precipitated using succinylated wheat germ agglutinin (sWGA). 24035784 9 71 theme germ 1419:1422 arg1 sWGA 1436:1439 sWGA 1436:1439 sWGA 1436:1439 O-GlcNAcylated proteins were detected by immunoblot using a specific antibody (ctd110.6) and were precipitated using succinylated wheat germ agglutinin (sWGA). 24035784 0 72 theme nuclear 63:69 arg1 apoptosis 71:79 nuclear apoptosis 63:79 nuclear apoptosis in T cells 63:90 Implications of the O-GlcNAc modification in the regulation of nuclear apoptosis in T cells. 24035784 4 73 dep levels 662:667 arg1 played 669:674 played 669:674 played a protective role in primary neonatal rat ventricular myocytes 669:737 The effects of O-GlcNAcylation on apoptosis appear to be cell-dependent, as elevated levels played a protective role in primary neonatal rat ventricular myocytes but had a cytotoxic effect in rat pancreatic β-cells. 24035784 4 73 dep levels 662:667 arg1 had 743:745 had 743:745 had a cytotoxic effect in rat pancreatic β-cells 743:790 The effects of O-GlcNAcylation on apoptosis appear to be cell-dependent, as elevated levels played a protective role in primary neonatal rat ventricular myocytes but had a cytotoxic effect in rat pancreatic β-cells. 24035784 4 74 theme rat 714:716 arg1 myocytes 730:737 primary neonatal rat ventricular myocytes 697:737 primary neonatal rat ventricular myocytes 697:737 The effects of O-GlcNAcylation on apoptosis appear to be cell-dependent, as elevated levels played a protective role in primary neonatal rat ventricular myocytes but had a cytotoxic effect in rat pancreatic β-cells. 24035784 4 75 theme protective 678:687 arg1 role 689:692 a protective role 676:692 a protective role 676:692 The effects of O-GlcNAcylation on apoptosis appear to be cell-dependent, as elevated levels played a protective role in primary neonatal rat ventricular myocytes but had a cytotoxic effect in rat pancreatic β-cells. 24035784 5 76 theme current 808:814 arg1 study 816:820 the current study 804:820 the current study 804:820 The aim of the current study was to determine the implications of the O-GlcNAc modification on T cell apoptosis. 24035784 6 77 theme OGA 972:974 arg1 PUGNAc 1057:1062 the OGA inhibitor O-(2-acetamido-2-deoxy-d-glucopyranosylidene) amino-N-phenylcarbamate (PUGNAc) 968:1063 the OGA inhibitor O-(2-acetamido-2-deoxy-d-glucopyranosylidene) amino-N-phenylcarbamate (PUGNAc) 968:1063 METHODS Human T lymphoblastic HPB-ALL cells were treated with the OGA inhibitor O-(2-acetamido-2-deoxy-d-glucopyranosylidene) amino-N-phenylcarbamate (PUGNAc), or with glucosamine (GlcN), to increase O-GlcNAcylation. 24035784 5 78 theme modification 872:883 arg1 implications 843:854 the implications 839:854 the implications of the O-GlcNAc modification on T cell apoptosis 839:903 The aim of the current study was to determine the implications of the O-GlcNAc modification on T cell apoptosis. 24035784 14 79 theme SIGNIFICANCE 1876:1887 arg1 results 1893:1899 GENERAL SIGNIFICANCE Our results 1868:1899 GENERAL SIGNIFICANCE Our results 1868:1899 GENERAL SIGNIFICANCE Our results indicate that the O-GlcNAcylation of DFF45 may represent a mechanism to control the accidental activation of DFF. 24035784 7 80 dep tributyltin 1164:1174 arg1 presence 1152:1159 presence 1152:1159 presence 1152:1159 Apoptosis was induced in the presence of tributyltin (TBT). 24035784 7 80 dep tributyltin 1164:1174 arg1 the 1148:1150 the 1148:1150 the 1148:1150 Apoptosis was induced in the presence of tributyltin (TBT). 24035784 10 81 from reduction 1509:1517 arg1 fragmentation 1526:1538 DNA fragmentation 1522:1538 DNA fragmentation 1522:1538 RESULTS HPB-ALL cells treated with PUGNAc displayed a significant reduction in DNA fragmentation after TBT-induced apoptosis. 27226773 5 0 theme murine 728:733 arg1 line 762:765 the murine 4T1 mammary carcinoma cell line 724:765 the murine 4T1 mammary carcinoma cell line 724:765 Comparisons of the protein profiles of the murine 4T1 mammary carcinoma cell line and a normal murine MM3MG mammary cell line indicated that cadherin-1 (CDH), collagenase 3 (MMP-13), Viral envelope protein G7e (VEP), Gag protein (GAG) and Hypothetical protein LOC433182 (LOC) were uniquely expressed by the 4T1 cells, and pigment epithelium-derived factor (PEDF) was exclusively secreted by the MM3MG cells. 27226773 4 1 theme murine 649:654 arg1 line 679:682 a murine mammary carcinoma cell line 647:682 a murine mammary carcinoma cell line 647:682 Two-dimensional electrophoresis (2D-E) coupled with lectin-based analysis followed by mass spectrometry were applied to identify potential biomarkers in the secretions of a murine mammary carcinoma cell line. 27226773 7 2 theme lectin-based 1346:1357 arg1 analysis 1359:1366 lectin-based analysis 1346:1366 lectin-based analysis 1346:1366 These differentially expressed N- and O-linked glycoprotein candidates, which were identified by combining lectin-based analysis with 2D-E, could serve as potential diagnostic and prognostic markers for breast cancer. 27226773 2 3 theme stage 295:299 arg1 diagnoses 301:309 late stage diagnoses 290:309 late stage diagnoses 290:309 Breast cancer is also one of the leading causes of death primarily due to late stage diagnoses and a lack of effective treatments. 27226773 0 4 theme Carcinoma 67:75 arg1 Cells 77:81 4T1 Murine Mammary Carcinoma Cells 48:81 4T1 Murine Mammary Carcinoma Cells 48:81 Secretion of N- and O-linked Glycoproteins from 4T1 Murine Mammary Carcinoma Cells. 27226773 5 5 theme pigment 1007:1013 arg1 PEDF 1042:1045 PEDF 1042:1045 PEDF 1042:1045 Comparisons of the protein profiles of the murine 4T1 mammary carcinoma cell line and a normal murine MM3MG mammary cell line indicated that cadherin-1 (CDH), collagenase 3 (MMP-13), Viral envelope protein G7e (VEP), Gag protein (GAG) and Hypothetical protein LOC433182 (LOC) were uniquely expressed by the 4T1 cells, and pigment epithelium-derived factor (PEDF) was exclusively secreted by the MM3MG cells. 27226773 5 5 theme pigment 1007:1013 arg1 factor 1034:1039 pigment epithelium-derived factor 1007:1039 pigment epithelium-derived factor (PEDF) 1007:1046 Comparisons of the protein profiles of the murine 4T1 mammary carcinoma cell line and a normal murine MM3MG mammary cell line indicated that cadherin-1 (CDH), collagenase 3 (MMP-13), Viral envelope protein G7e (VEP), Gag protein (GAG) and Hypothetical protein LOC433182 (LOC) were uniquely expressed by the 4T1 cells, and pigment epithelium-derived factor (PEDF) was exclusively secreted by the MM3MG cells. 27226773 2 6 theme late 290:293 arg1 diagnoses 301:309 late stage diagnoses 290:309 late stage diagnoses 290:309 Breast cancer is also one of the leading causes of death primarily due to late stage diagnoses and a lack of effective treatments. 27226773 4 7 theme lectin-based 528:539 arg1 analysis 541:548 lectin-based analysis 528:548 lectin-based analysis followed by mass spectrometry 528:578 Two-dimensional electrophoresis (2D-E) coupled with lectin-based analysis followed by mass spectrometry were applied to identify potential biomarkers in the secretions of a murine mammary carcinoma cell line. 27226773 5 8 theme Gag 902:904 arg1 protein 906:912 Gag protein 902:912 Gag protein (GAG) 902:918 Comparisons of the protein profiles of the murine 4T1 mammary carcinoma cell line and a normal murine MM3MG mammary cell line indicated that cadherin-1 (CDH), collagenase 3 (MMP-13), Viral envelope protein G7e (VEP), Gag protein (GAG) and Hypothetical protein LOC433182 (LOC) were uniquely expressed by the 4T1 cells, and pigment epithelium-derived factor (PEDF) was exclusively secreted by the MM3MG cells. 27226773 5 8 theme Gag 902:904 arg1 GAG 915:917 GAG 915:917 GAG 915:917 Comparisons of the protein profiles of the murine 4T1 mammary carcinoma cell line and a normal murine MM3MG mammary cell line indicated that cadherin-1 (CDH), collagenase 3 (MMP-13), Viral envelope protein G7e (VEP), Gag protein (GAG) and Hypothetical protein LOC433182 (LOC) were uniquely expressed by the 4T1 cells, and pigment epithelium-derived factor (PEDF) was exclusively secreted by the MM3MG cells. 27226773 6 9 theme O-glycosylated 1157:1170 arg1 CDH 1172:1174 aberrant O-glycosylated CDH 1148:1174 aberrant O-glycosylated CDH 1148:1174 Further analysis by a lectin-based study revealed that aberrant O-glycosylated CDH, N-glycosylated MMP-13 and LOC were present in the 4T1 medium. 27226773 5 10 theme cell 757:760 arg1 line 762:765 the murine 4T1 mammary carcinoma cell line 724:765 the murine 4T1 mammary carcinoma cell line 724:765 Comparisons of the protein profiles of the murine 4T1 mammary carcinoma cell line and a normal murine MM3MG mammary cell line indicated that cadherin-1 (CDH), collagenase 3 (MMP-13), Viral envelope protein G7e (VEP), Gag protein (GAG) and Hypothetical protein LOC433182 (LOC) were uniquely expressed by the 4T1 cells, and pigment epithelium-derived factor (PEDF) was exclusively secreted by the MM3MG cells. 27226773 5 11 theme protein 883:889 arg1 VEP 896:898 VEP 896:898 VEP 896:898 Comparisons of the protein profiles of the murine 4T1 mammary carcinoma cell line and a normal murine MM3MG mammary cell line indicated that cadherin-1 (CDH), collagenase 3 (MMP-13), Viral envelope protein G7e (VEP), Gag protein (GAG) and Hypothetical protein LOC433182 (LOC) were uniquely expressed by the 4T1 cells, and pigment epithelium-derived factor (PEDF) was exclusively secreted by the MM3MG cells. 27226773 5 11 theme protein 883:889 arg1 G7e 891:893 Viral envelope protein G7e 868:893 Viral envelope protein G7e (VEP) 868:899 Comparisons of the protein profiles of the murine 4T1 mammary carcinoma cell line and a normal murine MM3MG mammary cell line indicated that cadherin-1 (CDH), collagenase 3 (MMP-13), Viral envelope protein G7e (VEP), Gag protein (GAG) and Hypothetical protein LOC433182 (LOC) were uniquely expressed by the 4T1 cells, and pigment epithelium-derived factor (PEDF) was exclusively secreted by the MM3MG cells. 27226773 6 12 from medium 1231:1236 arg1 present 1212:1218 present 1212:1218 present 1212:1218 Further analysis by a lectin-based study revealed that aberrant O-glycosylated CDH, N-glycosylated MMP-13 and LOC were present in the 4T1 medium. 27226773 6 13 theme aberrant 1148:1155 arg1 CDH 1172:1174 aberrant O-glycosylated CDH 1148:1174 aberrant O-glycosylated CDH 1148:1174 Further analysis by a lectin-based study revealed that aberrant O-glycosylated CDH, N-glycosylated MMP-13 and LOC were present in the 4T1 medium. 27226773 4 14 theme carcinoma 664:672 arg1 line 679:682 a murine mammary carcinoma cell line 647:682 a murine mammary carcinoma cell line 647:682 Two-dimensional electrophoresis (2D-E) coupled with lectin-based analysis followed by mass spectrometry were applied to identify potential biomarkers in the secretions of a murine mammary carcinoma cell line. 27226773 7 15 theme potential 1394:1402 arg1 candidates 1299:1308 O-linked glycoprotein candidates 1277:1308 O-linked glycoprotein candidates 1277:1308 These differentially expressed N- and O-linked glycoprotein candidates, which were identified by combining lectin-based analysis with 2D-E, could serve as potential diagnostic and prognostic markers for breast cancer. 27226773 7 15 theme potential 1394:1402 arg1 markers 1430:1436 potential diagnostic and prognostic markers 1394:1436 potential diagnostic and prognostic markers for breast cancer 1394:1454 These differentially expressed N- and O-linked glycoprotein candidates, which were identified by combining lectin-based analysis with 2D-E, could serve as potential diagnostic and prognostic markers for breast cancer. 27226773 7 15 theme potential 1394:1402 arg1 N- 1270:1271 These differentially expressed N- 1239:1271 These differentially expressed N- 1239:1271 These differentially expressed N- and O-linked glycoprotein candidates, which were identified by combining lectin-based analysis with 2D-E, could serve as potential diagnostic and prognostic markers for breast cancer. 27226773 5 16 theme protein 704:710 arg1 profiles 712:719 the protein profiles 700:719 the protein profiles of the murine 4T1 mammary carcinoma cell line and a normal murine MM3MG mammary cell line 700:809 Comparisons of the protein profiles of the murine 4T1 mammary carcinoma cell line and a normal murine MM3MG mammary cell line indicated that cadherin-1 (CDH), collagenase 3 (MMP-13), Viral envelope protein G7e (VEP), Gag protein (GAG) and Hypothetical protein LOC433182 (LOC) were uniquely expressed by the 4T1 cells, and pigment epithelium-derived factor (PEDF) was exclusively secreted by the MM3MG cells. 27226773 5 17 theme mammary 793:799 arg1 line 806:809 a normal murine MM3MG mammary cell line 771:809 a normal murine MM3MG mammary cell line 771:809 Comparisons of the protein profiles of the murine 4T1 mammary carcinoma cell line and a normal murine MM3MG mammary cell line indicated that cadherin-1 (CDH), collagenase 3 (MMP-13), Viral envelope protein G7e (VEP), Gag protein (GAG) and Hypothetical protein LOC433182 (LOC) were uniquely expressed by the 4T1 cells, and pigment epithelium-derived factor (PEDF) was exclusively secreted by the MM3MG cells. 27226773 3 18 theme early 417:421 arg1 detection 423:431 early detection 417:431 early detection 417:431 Therefore, discovering protein expression biomarkers is mandatory for early detection and thus, critical for successful therapy. 27226773 6 19 attach present 1212:1218 arg2 CDH 1172:1174 aberrant O-glycosylated CDH 1148:1174 aberrant O-glycosylated CDH 1148:1174 Further analysis by a lectin-based study revealed that aberrant O-glycosylated CDH, N-glycosylated MMP-13 and LOC were present in the 4T1 medium. 27226773 6 19 attach present 1212:1218 arg2 LOC 1203:1205 LOC 1203:1205 LOC 1203:1205 Further analysis by a lectin-based study revealed that aberrant O-glycosylated CDH, N-glycosylated MMP-13 and LOC were present in the 4T1 medium. 27226773 6 19 attach present 1212:1218 arg1 medium 1231:1236 the 4T1 medium 1223:1236 the 4T1 medium 1223:1236 Further analysis by a lectin-based study revealed that aberrant O-glycosylated CDH, N-glycosylated MMP-13 and LOC were present in the 4T1 medium. 27226773 6 19 attach present 1212:1218 arg2 MMP-13 1192:1197 N-glycosylated MMP-13 1177:1197 N-glycosylated MMP-13 1177:1197 Further analysis by a lectin-based study revealed that aberrant O-glycosylated CDH, N-glycosylated MMP-13 and LOC were present in the 4T1 medium. 27226773 2 20 theme effective 325:333 arg1 treatments 335:344 effective treatments 325:344 effective treatments 325:344 Breast cancer is also one of the leading causes of death primarily due to late stage diagnoses and a lack of effective treatments. 27226773 5 21 theme profiles 712:719 arg1 Comparisons 685:695 Comparisons 685:695 Comparisons of the protein profiles of the murine 4T1 mammary carcinoma cell line and a normal murine MM3MG mammary cell line 685:809 Comparisons of the protein profiles of the murine 4T1 mammary carcinoma cell line and a normal murine MM3MG mammary cell line indicated that cadherin-1 (CDH), collagenase 3 (MMP-13), Viral envelope protein G7e (VEP), Gag protein (GAG) and Hypothetical protein LOC433182 (LOC) were uniquely expressed by the 4T1 cells, and pigment epithelium-derived factor (PEDF) was exclusively secreted by the MM3MG cells. 27226773 5 22 theme 4T1 992:994 arg1 cells 996:1000 the 4T1 cells 988:1000 the 4T1 cells 988:1000 Comparisons of the protein profiles of the murine 4T1 mammary carcinoma cell line and a normal murine MM3MG mammary cell line indicated that cadherin-1 (CDH), collagenase 3 (MMP-13), Viral envelope protein G7e (VEP), Gag protein (GAG) and Hypothetical protein LOC433182 (LOC) were uniquely expressed by the 4T1 cells, and pigment epithelium-derived factor (PEDF) was exclusively secreted by the MM3MG cells. 27226773 5 23 theme mammary 739:745 arg1 line 762:765 the murine 4T1 mammary carcinoma cell line 724:765 the murine 4T1 mammary carcinoma cell line 724:765 Comparisons of the protein profiles of the murine 4T1 mammary carcinoma cell line and a normal murine MM3MG mammary cell line indicated that cadherin-1 (CDH), collagenase 3 (MMP-13), Viral envelope protein G7e (VEP), Gag protein (GAG) and Hypothetical protein LOC433182 (LOC) were uniquely expressed by the 4T1 cells, and pigment epithelium-derived factor (PEDF) was exclusively secreted by the MM3MG cells. 27226773 7 24 gly glycoprotein 1286:1297 arg1 glycoprotein 1286:1297 O-linked glycoprotein candidates 1277:1308 O-linked glycoprotein candidates 1277:1308 These differentially expressed N- and O-linked glycoprotein candidates, which were identified by combining lectin-based analysis with 2D-E, could serve as potential diagnostic and prognostic markers for breast cancer. 27226773 4 25 theme mass 562:565 arg1 spectrometry 567:578 mass spectrometry 562:578 mass spectrometry 562:578 Two-dimensional electrophoresis (2D-E) coupled with lectin-based analysis followed by mass spectrometry were applied to identify potential biomarkers in the secretions of a murine mammary carcinoma cell line. 27226773 5 26 theme 4T1 735:737 arg1 line 762:765 the murine 4T1 mammary carcinoma cell line 724:765 the murine 4T1 mammary carcinoma cell line 724:765 Comparisons of the protein profiles of the murine 4T1 mammary carcinoma cell line and a normal murine MM3MG mammary cell line indicated that cadherin-1 (CDH), collagenase 3 (MMP-13), Viral envelope protein G7e (VEP), Gag protein (GAG) and Hypothetical protein LOC433182 (LOC) were uniquely expressed by the 4T1 cells, and pigment epithelium-derived factor (PEDF) was exclusively secreted by the MM3MG cells. 27226773 6 27 located present 1212:1218 arg2 CDH 1172:1174 aberrant O-glycosylated CDH 1148:1174 aberrant O-glycosylated CDH 1148:1174 Further analysis by a lectin-based study revealed that aberrant O-glycosylated CDH, N-glycosylated MMP-13 and LOC were present in the 4T1 medium. 27226773 6 27 located present 1212:1218 arg2 LOC 1203:1205 LOC 1203:1205 LOC 1203:1205 Further analysis by a lectin-based study revealed that aberrant O-glycosylated CDH, N-glycosylated MMP-13 and LOC were present in the 4T1 medium. 27226773 6 27 located present 1212:1218 arg1 medium 1231:1236 the 4T1 medium 1223:1236 the 4T1 medium 1223:1236 Further analysis by a lectin-based study revealed that aberrant O-glycosylated CDH, N-glycosylated MMP-13 and LOC were present in the 4T1 medium. 27226773 6 27 located present 1212:1218 arg2 MMP-13 1192:1197 N-glycosylated MMP-13 1177:1197 N-glycosylated MMP-13 1177:1197 Further analysis by a lectin-based study revealed that aberrant O-glycosylated CDH, N-glycosylated MMP-13 and LOC were present in the 4T1 medium. 27226773 7 28 link O-linked 1277:1284 arg1 candidates 1299:1308 O-linked glycoprotein candidates 1277:1308 O-linked glycoprotein candidates 1277:1308 These differentially expressed N- and O-linked glycoprotein candidates, which were identified by combining lectin-based analysis with 2D-E, could serve as potential diagnostic and prognostic markers for breast cancer. 27226773 7 28 link O-linked 1277:1284 arg1 markers 1430:1436 potential diagnostic and prognostic markers 1394:1436 potential diagnostic and prognostic markers for breast cancer 1394:1454 These differentially expressed N- and O-linked glycoprotein candidates, which were identified by combining lectin-based analysis with 2D-E, could serve as potential diagnostic and prognostic markers for breast cancer. 27226773 7 28 link O-linked 1277:1284 arg1 N- 1270:1271 These differentially expressed N- 1239:1271 These differentially expressed N- 1239:1271 These differentially expressed N- and O-linked glycoprotein candidates, which were identified by combining lectin-based analysis with 2D-E, could serve as potential diagnostic and prognostic markers for breast cancer. 27226773 6 29 gly N-glycosylated 1177:1190 arg1 MMP-13 1192:1197 N-glycosylated MMP-13 1177:1197 N-glycosylated MMP-13 1177:1197 Further analysis by a lectin-based study revealed that aberrant O-glycosylated CDH, N-glycosylated MMP-13 and LOC were present in the 4T1 medium. 27226773 6 30 from present 1212:1218 arg1 medium 1231:1236 the 4T1 medium 1223:1236 the 4T1 medium 1223:1236 Further analysis by a lectin-based study revealed that aberrant O-glycosylated CDH, N-glycosylated MMP-13 and LOC were present in the 4T1 medium. 27226773 6 31 theme lectin-based 1115:1126 arg1 study 1128:1132 a lectin-based study 1113:1132 a lectin-based study 1113:1132 Further analysis by a lectin-based study revealed that aberrant O-glycosylated CDH, N-glycosylated MMP-13 and LOC were present in the 4T1 medium. 27226773 2 32 theme causes 257:262 arg1 one 238:240 one 238:240 one 238:240 Breast cancer is also one of the leading causes of death primarily due to late stage diagnoses and a lack of effective treatments. 27226773 2 32 theme causes 257:262 arg1 causes 257:262 the leading causes 245:262 the leading causes of death 245:271 Breast cancer is also one of the leading causes of death primarily due to late stage diagnoses and a lack of effective treatments. 27226773 4 33 from biomarkers 615:624 arg1 secretions 633:642 the secretions 629:642 the secretions of a murine mammary carcinoma cell line 629:682 Two-dimensional electrophoresis (2D-E) coupled with lectin-based analysis followed by mass spectrometry were applied to identify potential biomarkers in the secretions of a murine mammary carcinoma cell line. 27226773 3 34 theme protein 370:376 arg1 biomarkers 389:398 protein expression biomarkers 370:398 protein expression biomarkers 370:398 Therefore, discovering protein expression biomarkers is mandatory for early detection and thus, critical for successful therapy. 27226773 5 35 theme normal 773:778 arg1 line 806:809 a normal murine MM3MG mammary cell line 771:809 a normal murine MM3MG mammary cell line 771:809 Comparisons of the protein profiles of the murine 4T1 mammary carcinoma cell line and a normal murine MM3MG mammary cell line indicated that cadherin-1 (CDH), collagenase 3 (MMP-13), Viral envelope protein G7e (VEP), Gag protein (GAG) and Hypothetical protein LOC433182 (LOC) were uniquely expressed by the 4T1 cells, and pigment epithelium-derived factor (PEDF) was exclusively secreted by the MM3MG cells. 27226773 6 36 theme 4T1 1227:1229 arg1 medium 1231:1236 the 4T1 medium 1223:1236 the 4T1 medium 1223:1236 Further analysis by a lectin-based study revealed that aberrant O-glycosylated CDH, N-glycosylated MMP-13 and LOC were present in the 4T1 medium. 27226773 0 37 link O-linked 20:27 arg1 Glycoproteins 29:41 N- and O-linked Glycoproteins 13:41 N- and O-linked Glycoproteins 13:41 Secretion of N- and O-linked Glycoproteins from 4T1 Murine Mammary Carcinoma Cells. 27226773 2 38 theme leading 249:255 arg1 causes 257:262 the leading causes 245:262 the leading causes of death 245:271 Breast cancer is also one of the leading causes of death primarily due to late stage diagnoses and a lack of effective treatments. 27226773 5 39 link epithelium-derived 1015:1032 arg1 PEDF 1042:1045 PEDF 1042:1045 PEDF 1042:1045 Comparisons of the protein profiles of the murine 4T1 mammary carcinoma cell line and a normal murine MM3MG mammary cell line indicated that cadherin-1 (CDH), collagenase 3 (MMP-13), Viral envelope protein G7e (VEP), Gag protein (GAG) and Hypothetical protein LOC433182 (LOC) were uniquely expressed by the 4T1 cells, and pigment epithelium-derived factor (PEDF) was exclusively secreted by the MM3MG cells. 27226773 5 39 link epithelium-derived 1015:1032 arg1 factor 1034:1039 pigment epithelium-derived factor 1007:1039 pigment epithelium-derived factor (PEDF) 1007:1046 Comparisons of the protein profiles of the murine 4T1 mammary carcinoma cell line and a normal murine MM3MG mammary cell line indicated that cadherin-1 (CDH), collagenase 3 (MMP-13), Viral envelope protein G7e (VEP), Gag protein (GAG) and Hypothetical protein LOC433182 (LOC) were uniquely expressed by the 4T1 cells, and pigment epithelium-derived factor (PEDF) was exclusively secreted by the MM3MG cells. 27226773 5 40 theme MM3MG 787:791 arg1 line 806:809 a normal murine MM3MG mammary cell line 771:809 a normal murine MM3MG mammary cell line 771:809 Comparisons of the protein profiles of the murine 4T1 mammary carcinoma cell line and a normal murine MM3MG mammary cell line indicated that cadherin-1 (CDH), collagenase 3 (MMP-13), Viral envelope protein G7e (VEP), Gag protein (GAG) and Hypothetical protein LOC433182 (LOC) were uniquely expressed by the 4T1 cells, and pigment epithelium-derived factor (PEDF) was exclusively secreted by the MM3MG cells. 27226773 1 41 theme Breast 84:89 arg1 cancer 91:96 Breast cancer 84:96 Breast cancer 84:96 Breast cancer is one of the most common cancers that affect women globally and accounts for ~23% of all cancers diagnosed in women. 27226773 5 42 theme Viral 868:872 arg1 VEP 896:898 VEP 896:898 VEP 896:898 Comparisons of the protein profiles of the murine 4T1 mammary carcinoma cell line and a normal murine MM3MG mammary cell line indicated that cadherin-1 (CDH), collagenase 3 (MMP-13), Viral envelope protein G7e (VEP), Gag protein (GAG) and Hypothetical protein LOC433182 (LOC) were uniquely expressed by the 4T1 cells, and pigment epithelium-derived factor (PEDF) was exclusively secreted by the MM3MG cells. 27226773 5 42 theme Viral 868:872 arg1 G7e 891:893 Viral envelope protein G7e 868:893 Viral envelope protein G7e (VEP) 868:899 Comparisons of the protein profiles of the murine 4T1 mammary carcinoma cell line and a normal murine MM3MG mammary cell line indicated that cadherin-1 (CDH), collagenase 3 (MMP-13), Viral envelope protein G7e (VEP), Gag protein (GAG) and Hypothetical protein LOC433182 (LOC) were uniquely expressed by the 4T1 cells, and pigment epithelium-derived factor (PEDF) was exclusively secreted by the MM3MG cells. 27226773 0 43 from Cells 77:81 arg1 Secretion 0:8 Secretion 0:8 Secretion of N- and O-linked Glycoproteins from 4T1 Murine Mammary Carcinoma Cells. 0:82 Secretion of N- and O-linked Glycoproteins from 4T1 Murine Mammary Carcinoma Cells. 27226773 4 44 theme mammary 656:662 arg1 line 679:682 a murine mammary carcinoma cell line 647:682 a murine mammary carcinoma cell line 647:682 Two-dimensional electrophoresis (2D-E) coupled with lectin-based analysis followed by mass spectrometry were applied to identify potential biomarkers in the secretions of a murine mammary carcinoma cell line. 27226773 3 45 theme successful 456:465 arg1 therapy 467:473 successful therapy 456:473 successful therapy 456:473 Therefore, discovering protein expression biomarkers is mandatory for early detection and thus, critical for successful therapy. 27226773 0 46 theme Glycoproteins 29:41 arg1 Secretion 0:8 Secretion 0:8 Secretion of N- and O-linked Glycoproteins from 4T1 Murine Mammary Carcinoma Cells. 0:82 Secretion of N- and O-linked Glycoproteins from 4T1 Murine Mammary Carcinoma Cells. 27226773 7 47 theme breast 1442:1447 arg1 cancer 1449:1454 breast cancer 1442:1454 breast cancer 1442:1454 These differentially expressed N- and O-linked glycoprotein candidates, which were identified by combining lectin-based analysis with 2D-E, could serve as potential diagnostic and prognostic markers for breast cancer. 27226773 7 48 theme O-linked 1277:1284 arg1 candidates 1299:1308 O-linked glycoprotein candidates 1277:1308 O-linked glycoprotein candidates 1277:1308 These differentially expressed N- and O-linked glycoprotein candidates, which were identified by combining lectin-based analysis with 2D-E, could serve as potential diagnostic and prognostic markers for breast cancer. 27226773 7 48 theme O-linked 1277:1284 arg1 markers 1430:1436 potential diagnostic and prognostic markers 1394:1436 potential diagnostic and prognostic markers for breast cancer 1394:1454 These differentially expressed N- and O-linked glycoprotein candidates, which were identified by combining lectin-based analysis with 2D-E, could serve as potential diagnostic and prognostic markers for breast cancer. 27226773 7 48 theme O-linked 1277:1284 arg1 N- 1270:1271 These differentially expressed N- 1239:1271 These differentially expressed N- 1239:1271 These differentially expressed N- and O-linked glycoprotein candidates, which were identified by combining lectin-based analysis with 2D-E, could serve as potential diagnostic and prognostic markers for breast cancer. 27226773 5 49 theme cell 801:804 arg1 line 806:809 a normal murine MM3MG mammary cell line 771:809 a normal murine MM3MG mammary cell line 771:809 Comparisons of the protein profiles of the murine 4T1 mammary carcinoma cell line and a normal murine MM3MG mammary cell line indicated that cadherin-1 (CDH), collagenase 3 (MMP-13), Viral envelope protein G7e (VEP), Gag protein (GAG) and Hypothetical protein LOC433182 (LOC) were uniquely expressed by the 4T1 cells, and pigment epithelium-derived factor (PEDF) was exclusively secreted by the MM3MG cells. 27226773 0 50 theme O-linked 20:27 arg1 Glycoproteins 29:41 N- and O-linked Glycoproteins 13:41 N- and O-linked Glycoproteins 13:41 Secretion of N- and O-linked Glycoproteins from 4T1 Murine Mammary Carcinoma Cells. 27226773 4 51 theme Two-dimensional 476:490 arg1 electrophoresis 492:506 Two-dimensional electrophoresis 476:506 Two-dimensional electrophoresis (2D-E) coupled with lectin-based analysis followed by mass spectrometry 476:578 Two-dimensional electrophoresis (2D-E) coupled with lectin-based analysis followed by mass spectrometry were applied to identify potential biomarkers in the secretions of a murine mammary carcinoma cell line. 27226773 4 51 theme Two-dimensional 476:490 arg1 2D-E 509:512 2D-E 509:512 2D-E 509:512 Two-dimensional electrophoresis (2D-E) coupled with lectin-based analysis followed by mass spectrometry were applied to identify potential biomarkers in the secretions of a murine mammary carcinoma cell line. 27226773 5 52 theme carcinoma 747:755 arg1 line 762:765 the murine 4T1 mammary carcinoma cell line 724:765 the murine 4T1 mammary carcinoma cell line 724:765 Comparisons of the protein profiles of the murine 4T1 mammary carcinoma cell line and a normal murine MM3MG mammary cell line indicated that cadherin-1 (CDH), collagenase 3 (MMP-13), Viral envelope protein G7e (VEP), Gag protein (GAG) and Hypothetical protein LOC433182 (LOC) were uniquely expressed by the 4T1 cells, and pigment epithelium-derived factor (PEDF) was exclusively secreted by the MM3MG cells. 27226773 7 53 theme prognostic 1419:1428 arg1 candidates 1299:1308 O-linked glycoprotein candidates 1277:1308 O-linked glycoprotein candidates 1277:1308 These differentially expressed N- and O-linked glycoprotein candidates, which were identified by combining lectin-based analysis with 2D-E, could serve as potential diagnostic and prognostic markers for breast cancer. 27226773 7 53 theme prognostic 1419:1428 arg1 markers 1430:1436 potential diagnostic and prognostic markers 1394:1436 potential diagnostic and prognostic markers for breast cancer 1394:1454 These differentially expressed N- and O-linked glycoprotein candidates, which were identified by combining lectin-based analysis with 2D-E, could serve as potential diagnostic and prognostic markers for breast cancer. 27226773 7 53 theme prognostic 1419:1428 arg1 N- 1270:1271 These differentially expressed N- 1239:1271 These differentially expressed N- 1239:1271 These differentially expressed N- and O-linked glycoprotein candidates, which were identified by combining lectin-based analysis with 2D-E, could serve as potential diagnostic and prognostic markers for breast cancer. 27226773 5 54 theme line 806:809 arg1 profiles 712:719 the protein profiles 700:719 the protein profiles of the murine 4T1 mammary carcinoma cell line and a normal murine MM3MG mammary cell line 700:809 Comparisons of the protein profiles of the murine 4T1 mammary carcinoma cell line and a normal murine MM3MG mammary cell line indicated that cadherin-1 (CDH), collagenase 3 (MMP-13), Viral envelope protein G7e (VEP), Gag protein (GAG) and Hypothetical protein LOC433182 (LOC) were uniquely expressed by the 4T1 cells, and pigment epithelium-derived factor (PEDF) was exclusively secreted by the MM3MG cells. 27226773 2 55 theme treatments 335:344 arg1 diagnoses 301:309 late stage diagnoses 290:309 late stage diagnoses 290:309 Breast cancer is also one of the leading causes of death primarily due to late stage diagnoses and a lack of effective treatments. 27226773 2 55 theme treatments 335:344 arg1 lack 317:320 a lack 315:320 a lack of effective treatments 315:344 Breast cancer is also one of the leading causes of death primarily due to late stage diagnoses and a lack of effective treatments. 27226773 0 56 theme 4T1 48:50 arg1 Cells 77:81 4T1 Murine Mammary Carcinoma Cells 48:81 4T1 Murine Mammary Carcinoma Cells 48:81 Secretion of N- and O-linked Glycoproteins from 4T1 Murine Mammary Carcinoma Cells. 27226773 5 57 theme murine 780:785 arg1 line 806:809 a normal murine MM3MG mammary cell line 771:809 a normal murine MM3MG mammary cell line 771:809 Comparisons of the protein profiles of the murine 4T1 mammary carcinoma cell line and a normal murine MM3MG mammary cell line indicated that cadherin-1 (CDH), collagenase 3 (MMP-13), Viral envelope protein G7e (VEP), Gag protein (GAG) and Hypothetical protein LOC433182 (LOC) were uniquely expressed by the 4T1 cells, and pigment epithelium-derived factor (PEDF) was exclusively secreted by the MM3MG cells. 27226773 3 58 theme expression 378:387 arg1 biomarkers 389:398 protein expression biomarkers 370:398 protein expression biomarkers 370:398 Therefore, discovering protein expression biomarkers is mandatory for early detection and thus, critical for successful therapy. 27226773 4 59 theme line 679:682 arg1 secretions 633:642 the secretions 629:642 the secretions of a murine mammary carcinoma cell line 629:682 Two-dimensional electrophoresis (2D-E) coupled with lectin-based analysis followed by mass spectrometry were applied to identify potential biomarkers in the secretions of a murine mammary carcinoma cell line. 27226773 5 60 theme line 762:765 arg1 profiles 712:719 the protein profiles 700:719 the protein profiles of the murine 4T1 mammary carcinoma cell line and a normal murine MM3MG mammary cell line 700:809 Comparisons of the protein profiles of the murine 4T1 mammary carcinoma cell line and a normal murine MM3MG mammary cell line indicated that cadherin-1 (CDH), collagenase 3 (MMP-13), Viral envelope protein G7e (VEP), Gag protein (GAG) and Hypothetical protein LOC433182 (LOC) were uniquely expressed by the 4T1 cells, and pigment epithelium-derived factor (PEDF) was exclusively secreted by the MM3MG cells. 27226773 7 61 theme diagnostic 1404:1413 arg1 candidates 1299:1308 O-linked glycoprotein candidates 1277:1308 O-linked glycoprotein candidates 1277:1308 These differentially expressed N- and O-linked glycoprotein candidates, which were identified by combining lectin-based analysis with 2D-E, could serve as potential diagnostic and prognostic markers for breast cancer. 27226773 7 61 theme diagnostic 1404:1413 arg1 markers 1430:1436 potential diagnostic and prognostic markers 1394:1436 potential diagnostic and prognostic markers for breast cancer 1394:1454 These differentially expressed N- and O-linked glycoprotein candidates, which were identified by combining lectin-based analysis with 2D-E, could serve as potential diagnostic and prognostic markers for breast cancer. 27226773 7 61 theme diagnostic 1404:1413 arg1 N- 1270:1271 These differentially expressed N- 1239:1271 These differentially expressed N- 1239:1271 These differentially expressed N- and O-linked glycoprotein candidates, which were identified by combining lectin-based analysis with 2D-E, could serve as potential diagnostic and prognostic markers for breast cancer. 27226773 5 62 theme Hypothetical 924:935 arg1 protein 937:943 Hypothetical protein LOC433182 924:953 Hypothetical protein LOC433182 (LOC) 924:959 Comparisons of the protein profiles of the murine 4T1 mammary carcinoma cell line and a normal murine MM3MG mammary cell line indicated that cadherin-1 (CDH), collagenase 3 (MMP-13), Viral envelope protein G7e (VEP), Gag protein (GAG) and Hypothetical protein LOC433182 (LOC) were uniquely expressed by the 4T1 cells, and pigment epithelium-derived factor (PEDF) was exclusively secreted by the MM3MG cells. 27226773 5 62 theme Hypothetical 924:935 arg1 LOC 956:958 LOC 956:958 LOC 956:958 Comparisons of the protein profiles of the murine 4T1 mammary carcinoma cell line and a normal murine MM3MG mammary cell line indicated that cadherin-1 (CDH), collagenase 3 (MMP-13), Viral envelope protein G7e (VEP), Gag protein (GAG) and Hypothetical protein LOC433182 (LOC) were uniquely expressed by the 4T1 cells, and pigment epithelium-derived factor (PEDF) was exclusively secreted by the MM3MG cells. 27226773 4 63 theme cell 674:677 arg1 line 679:682 a murine mammary carcinoma cell line 647:682 a murine mammary carcinoma cell line 647:682 Two-dimensional electrophoresis (2D-E) coupled with lectin-based analysis followed by mass spectrometry were applied to identify potential biomarkers in the secretions of a murine mammary carcinoma cell line. 27226773 6 64 theme Further 1093:1099 arg1 analysis 1101:1108 Further analysis 1093:1108 Further analysis by a lectin-based study 1093:1132 Further analysis by a lectin-based study revealed that aberrant O-glycosylated CDH, N-glycosylated MMP-13 and LOC were present in the 4T1 medium. 27226773 5 65 theme envelope 874:881 arg1 VEP 896:898 VEP 896:898 VEP 896:898 Comparisons of the protein profiles of the murine 4T1 mammary carcinoma cell line and a normal murine MM3MG mammary cell line indicated that cadherin-1 (CDH), collagenase 3 (MMP-13), Viral envelope protein G7e (VEP), Gag protein (GAG) and Hypothetical protein LOC433182 (LOC) were uniquely expressed by the 4T1 cells, and pigment epithelium-derived factor (PEDF) was exclusively secreted by the MM3MG cells. 27226773 5 65 theme envelope 874:881 arg1 G7e 891:893 Viral envelope protein G7e 868:893 Viral envelope protein G7e (VEP) 868:899 Comparisons of the protein profiles of the murine 4T1 mammary carcinoma cell line and a normal murine MM3MG mammary cell line indicated that cadherin-1 (CDH), collagenase 3 (MMP-13), Viral envelope protein G7e (VEP), Gag protein (GAG) and Hypothetical protein LOC433182 (LOC) were uniquely expressed by the 4T1 cells, and pigment epithelium-derived factor (PEDF) was exclusively secreted by the MM3MG cells. 27226773 6 66 gly O-glycosylated 1157:1170 arg1 CDH 1172:1174 aberrant O-glycosylated CDH 1148:1174 aberrant O-glycosylated CDH 1148:1174 Further analysis by a lectin-based study revealed that aberrant O-glycosylated CDH, N-glycosylated MMP-13 and LOC were present in the 4T1 medium. 27226773 6 67 theme N-glycosylated 1177:1190 arg1 MMP-13 1192:1197 N-glycosylated MMP-13 1177:1197 N-glycosylated MMP-13 1177:1197 Further analysis by a lectin-based study revealed that aberrant O-glycosylated CDH, N-glycosylated MMP-13 and LOC were present in the 4T1 medium. 27226773 2 68 theme Breast 216:221 arg1 cancer 223:228 Breast cancer 216:228 Breast cancer 216:228 Breast cancer is also one of the leading causes of death primarily due to late stage diagnoses and a lack of effective treatments. 27226773 2 69 theme death 267:271 arg1 causes 257:262 the leading causes 245:262 the leading causes of death 245:271 Breast cancer is also one of the leading causes of death primarily due to late stage diagnoses and a lack of effective treatments. 27226773 1 70 theme cancers 188:194 arg1 % 179:179 ~23% 176:179 ~23% of all cancers diagnosed in women 176:213 Breast cancer is one of the most common cancers that affect women globally and accounts for ~23% of all cancers diagnosed in women. 27226773 1 70 theme cancers 188:194 arg1 cancers 188:194 all cancers 184:194 all cancers diagnosed in women 184:213 Breast cancer is one of the most common cancers that affect women globally and accounts for ~23% of all cancers diagnosed in women. 27226773 0 71 theme Mammary 59:65 arg1 Cells 77:81 4T1 Murine Mammary Carcinoma Cells 48:81 4T1 Murine Mammary Carcinoma Cells 48:81 Secretion of N- and O-linked Glycoproteins from 4T1 Murine Mammary Carcinoma Cells. 27226773 4 72 theme potential 605:613 arg1 biomarkers 615:624 potential biomarkers 605:624 potential biomarkers in the secretions of a murine mammary carcinoma cell line 605:682 Two-dimensional electrophoresis (2D-E) coupled with lectin-based analysis followed by mass spectrometry were applied to identify potential biomarkers in the secretions of a murine mammary carcinoma cell line. 27226773 5 73 theme epithelium-derived 1015:1032 arg1 PEDF 1042:1045 PEDF 1042:1045 PEDF 1042:1045 Comparisons of the protein profiles of the murine 4T1 mammary carcinoma cell line and a normal murine MM3MG mammary cell line indicated that cadherin-1 (CDH), collagenase 3 (MMP-13), Viral envelope protein G7e (VEP), Gag protein (GAG) and Hypothetical protein LOC433182 (LOC) were uniquely expressed by the 4T1 cells, and pigment epithelium-derived factor (PEDF) was exclusively secreted by the MM3MG cells. 27226773 5 73 theme epithelium-derived 1015:1032 arg1 factor 1034:1039 pigment epithelium-derived factor 1007:1039 pigment epithelium-derived factor (PEDF) 1007:1046 Comparisons of the protein profiles of the murine 4T1 mammary carcinoma cell line and a normal murine MM3MG mammary cell line indicated that cadherin-1 (CDH), collagenase 3 (MMP-13), Viral envelope protein G7e (VEP), Gag protein (GAG) and Hypothetical protein LOC433182 (LOC) were uniquely expressed by the 4T1 cells, and pigment epithelium-derived factor (PEDF) was exclusively secreted by the MM3MG cells. 27226773 7 74 theme expressed 1260:1268 arg1 candidates 1299:1308 O-linked glycoprotein candidates 1277:1308 O-linked glycoprotein candidates 1277:1308 These differentially expressed N- and O-linked glycoprotein candidates, which were identified by combining lectin-based analysis with 2D-E, could serve as potential diagnostic and prognostic markers for breast cancer. 27226773 7 74 theme expressed 1260:1268 arg1 markers 1430:1436 potential diagnostic and prognostic markers 1394:1436 potential diagnostic and prognostic markers for breast cancer 1394:1454 These differentially expressed N- and O-linked glycoprotein candidates, which were identified by combining lectin-based analysis with 2D-E, could serve as potential diagnostic and prognostic markers for breast cancer. 27226773 7 74 theme expressed 1260:1268 arg1 N- 1270:1271 These differentially expressed N- 1239:1271 These differentially expressed N- 1239:1271 These differentially expressed N- and O-linked glycoprotein candidates, which were identified by combining lectin-based analysis with 2D-E, could serve as potential diagnostic and prognostic markers for breast cancer. 27226773 1 75 theme common 117:122 arg1 cancers 124:130 the most common cancers 108:130 the most common cancers that affect women globally and accounts for ~23% of all cancers diagnosed in women 108:213 Breast cancer is one of the most common cancers that affect women globally and accounts for ~23% of all cancers diagnosed in women. 27226773 0 76 theme Murine 52:57 arg1 Cells 77:81 4T1 Murine Mammary Carcinoma Cells 48:81 4T1 Murine Mammary Carcinoma Cells 48:81 Secretion of N- and O-linked Glycoproteins from 4T1 Murine Mammary Carcinoma Cells. 27226773 0 77 theme N- 13:14 arg1 Glycoproteins 29:41 N- and O-linked Glycoproteins 13:41 N- and O-linked Glycoproteins 13:41 Secretion of N- and O-linked Glycoproteins from 4T1 Murine Mammary Carcinoma Cells. 27226773 1 78 theme cancers 124:130 arg1 cancers 124:130 the most common cancers 108:130 the most common cancers that affect women globally and accounts for ~23% of all cancers diagnosed in women 108:213 Breast cancer is one of the most common cancers that affect women globally and accounts for ~23% of all cancers diagnosed in women. 27226773 1 78 theme cancers 124:130 arg1 one 101:103 one 101:103 one 101:103 Breast cancer is one of the most common cancers that affect women globally and accounts for ~23% of all cancers diagnosed in women. 27226773 7 79 theme glycoprotein 1286:1297 arg1 candidates 1299:1308 O-linked glycoprotein candidates 1277:1308 O-linked glycoprotein candidates 1277:1308 These differentially expressed N- and O-linked glycoprotein candidates, which were identified by combining lectin-based analysis with 2D-E, could serve as potential diagnostic and prognostic markers for breast cancer. 27226773 7 79 theme glycoprotein 1286:1297 arg1 markers 1430:1436 potential diagnostic and prognostic markers 1394:1436 potential diagnostic and prognostic markers for breast cancer 1394:1454 These differentially expressed N- and O-linked glycoprotein candidates, which were identified by combining lectin-based analysis with 2D-E, could serve as potential diagnostic and prognostic markers for breast cancer. 27226773 7 79 theme glycoprotein 1286:1297 arg1 N- 1270:1271 These differentially expressed N- 1239:1271 These differentially expressed N- 1239:1271 These differentially expressed N- and O-linked glycoprotein candidates, which were identified by combining lectin-based analysis with 2D-E, could serve as potential diagnostic and prognostic markers for breast cancer. 27226773 5 80 theme MM3MG 1080:1084 arg1 cells 1086:1090 the MM3MG cells 1076:1090 the MM3MG cells 1076:1090 Comparisons of the protein profiles of the murine 4T1 mammary carcinoma cell line and a normal murine MM3MG mammary cell line indicated that cadherin-1 (CDH), collagenase 3 (MMP-13), Viral envelope protein G7e (VEP), Gag protein (GAG) and Hypothetical protein LOC433182 (LOC) were uniquely expressed by the 4T1 cells, and pigment epithelium-derived factor (PEDF) was exclusively secreted by the MM3MG cells. 24333294 5 0 theme OA 819:820 arg1 chondrocytes 822:833 cultured human OA chondrocytes 804:833 cultured human OA chondrocytes 804:833 Our aim was to study whether O-GlcNAcylation and the enzymes responsible for this modification are dysregulated in the cartilage of patients with knee OA and whether interleukin-1 could induce these modifications in cultured human OA chondrocytes (HOC). 24333294 9 1 from O-GlcNAcylation 1265:1279 arg1 cartilage 1288:1296 the cartilage 1284:1296 the cartilage 1284:1296 RESULTS OA was associated with a 4-fold increase in the global O-GlcNAcylation in the cartilage. 24333294 8 2 theme key 1074:1076 arg1 enzymes 1078:1084 the key enzymes 1070:1084 the key enzymes responsible for this modification 1070:1118 Global protein O-GlcNAcylation and the synthesis of the key enzymes responsible for this modification, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), were assessed by western blot. 24333294 8 2 theme key 1074:1076 arg1 O-GlcNAcase 1152:1162 O-GlcNAcase 1152:1162 O-GlcNAcase (OGA) 1152:1168 Global protein O-GlcNAcylation and the synthesis of the key enzymes responsible for this modification, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), were assessed by western blot. 24333294 8 2 theme key 1074:1076 arg1 transferase 1130:1140 O-GlcNAc transferase 1121:1140 O-GlcNAc transferase (OGT) 1121:1146 Global protein O-GlcNAcylation and the synthesis of the key enzymes responsible for this modification, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), were assessed by western blot. 24333294 1 3 theme important 250:258 arg1 role 260:263 an important role 247:263 an important role 247:263 OBJECTIVE There is increasing evidence that the addition of O-linked N-acetylglucosamine (O-GlcNAc) to proteins plays an important role in cell signaling pathways. 24333294 3 4 from degradation 441:451 arg1 chondrocytes 495:506 hyaline chondrocytes 487:506 hyaline chondrocytes 487:506 Osteoarthritis (OA) is characterized by cartilage degradation, and hypertrophic-like changes in hyaline chondrocytes. 24333294 7 5 theme cytokine 1002:1009 arg1 IL-1α 1011:1015 the catabolic cytokine IL-1α 988:1015 the catabolic cytokine IL-1α 988:1015 HOC were cultured and stimulated with the catabolic cytokine IL-1α. 24333294 9 6 theme global 1258:1263 arg1 O-GlcNAcylation 1265:1279 the global O-GlcNAcylation 1254:1279 the global O-GlcNAcylation in the cartilage 1254:1296 RESULTS OA was associated with a 4-fold increase in the global O-GlcNAcylation in the cartilage. 24333294 10 7 theme healthy 1436:1442 arg1 cartilage 1444:1452 healthy cartilage 1436:1452 healthy cartilage 1436:1452 OA cartilage showed a re-distribution of the OGT and OGA isoforms, with a net increase in the presence of both enzymes, in comparison to healthy cartilage. 24333294 0 8 theme patients 94:101 arg1 cartilage 81:89 the cartilage 77:89 the cartilage of patients with knee osteoarthritis 77:126 O-linked N-acetylglucosamine (O-GlcNAc) protein modification is increased in the cartilage of patients with knee osteoarthritis. 24333294 8 9 theme responsible 1086:1096 arg1 enzymes 1078:1084 the key enzymes 1070:1084 the key enzymes responsible for this modification 1070:1118 Global protein O-GlcNAcylation and the synthesis of the key enzymes responsible for this modification, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), were assessed by western blot. 24333294 8 9 theme responsible 1086:1096 arg1 O-GlcNAcase 1152:1162 O-GlcNAcase 1152:1162 O-GlcNAcase (OGA) 1152:1168 Global protein O-GlcNAcylation and the synthesis of the key enzymes responsible for this modification, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), were assessed by western blot. 24333294 8 9 theme responsible 1086:1096 arg1 transferase 1130:1140 O-GlcNAc transferase 1121:1140 O-GlcNAc transferase (OGT) 1121:1146 Global protein O-GlcNAcylation and the synthesis of the key enzymes responsible for this modification, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), were assessed by western blot. 24333294 6 10 theme Human 849:853 arg1 cartilage 855:863 DESIGN Human cartilage 842:863 DESIGN Human cartilage 842:863 DESIGN Human cartilage was obtained from patients with knee OA and from age and sex-matched healthy donors. 24333294 1 11 dep OBJECTIVE 129:137 arg1 There 139:143 There 139:143 There 139:143 OBJECTIVE There is increasing evidence that the addition of O-linked N-acetylglucosamine (O-GlcNAc) to proteins plays an important role in cell signaling pathways. 24333294 6 12 theme healthy 934:940 arg1 donors 942:947 age and sex-matched healthy donors 914:947 age and sex-matched healthy donors 914:947 DESIGN Human cartilage was obtained from patients with knee OA and from age and sex-matched healthy donors. 24333294 8 13 theme enzymes 1078:1084 arg1 O-GlcNAcylation 1033:1047 Global protein O-GlcNAcylation 1018:1047 Global protein O-GlcNAcylation 1018:1047 Global protein O-GlcNAcylation and the synthesis of the key enzymes responsible for this modification, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), were assessed by western blot. 24333294 8 13 theme enzymes 1078:1084 arg1 synthesis 1057:1065 the synthesis 1053:1065 the synthesis of the key enzymes responsible for this modification, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), 1053:1169 Global protein O-GlcNAcylation and the synthesis of the key enzymes responsible for this modification, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), were assessed by western blot. 24333294 5 14 theme responsible 649:659 arg1 enzymes 641:647 the enzymes 637:647 the enzymes responsible for this modification 637:681 Our aim was to study whether O-GlcNAcylation and the enzymes responsible for this modification are dysregulated in the cartilage of patients with knee OA and whether interleukin-1 could induce these modifications in cultured human OA chondrocytes (HOC). 24333294 13 15 theme differentiation 1872:1886 arg1 markers 1888:1894 hypertrophic differentiation markers 1859:1894 hypertrophic differentiation markers that have been observed in OA 1859:1924 The increase in O-GlcNAcylation could be responsible, at least partially, for the re-expression of hypertrophic differentiation markers that have been observed in OA. 24333294 1 16 theme cell 268:271 arg1 pathways 283:290 cell signaling pathways 268:290 cell signaling pathways 268:290 OBJECTIVE There is increasing evidence that the addition of O-linked N-acetylglucosamine (O-GlcNAc) to proteins plays an important role in cell signaling pathways. 24333294 0 17 theme knee 108:111 arg1 osteoarthritis 113:126 knee osteoarthritis 108:126 knee osteoarthritis 108:126 O-linked N-acetylglucosamine (O-GlcNAc) protein modification is increased in the cartilage of patients with knee osteoarthritis. 24333294 6 18 theme sex-matched 922:932 arg1 donors 942:947 age and sex-matched healthy donors 914:947 age and sex-matched healthy donors 914:947 DESIGN Human cartilage was obtained from patients with knee OA and from age and sex-matched healthy donors. 24333294 0 19 link O-linked 0:7 arg1 O-GlcNAc 30:37 O-GlcNAc 30:37 O-GlcNAc 30:37 O-linked N-acetylglucosamine (O-GlcNAc) protein modification is increased in the cartilage of patients with knee osteoarthritis. 24333294 0 19 link O-linked 0:7 arg1 N-acetylglucosamine 9:27 O-linked N-acetylglucosamine 0:27 O-linked N-acetylglucosamine (O-GlcNAc) protein modification 0:59 O-linked N-acetylglucosamine (O-GlcNAc) protein modification is increased in the cartilage of patients with knee osteoarthritis. 24333294 12 20 theme OA 1664:1665 arg1 cartilage 1667:1675 OA cartilage 1664:1675 OA cartilage 1664:1675 CONCLUSIONS Our results indicate that a proinflammatory milieu could favor the accumulation of O-GlcNAcylated proteins in OA cartilage, together with the dysregulation of the enzymes responsible for this modification. 24333294 5 21 gly O-GlcNAcylation 617:631 arg1 cartilage 707:715 the cartilage 703:715 the cartilage of patients with knee OA 703:740 Our aim was to study whether O-GlcNAcylation and the enzymes responsible for this modification are dysregulated in the cartilage of patients with knee OA and whether interleukin-1 could induce these modifications in cultured human OA chondrocytes (HOC). 24333294 4 22 theme responsible 533:543 arg1 mechanisms 522:531 the mechanisms 518:531 the mechanisms responsible for these changes 518:561 However, the mechanisms responsible for these changes have not been described. 24333294 1 23 link O-linked 189:196 arg1 O-GlcNAc 219:226 O-GlcNAc 219:226 O-GlcNAc 219:226 OBJECTIVE There is increasing evidence that the addition of O-linked N-acetylglucosamine (O-GlcNAc) to proteins plays an important role in cell signaling pathways. 24333294 1 23 link O-linked 189:196 arg1 N-acetylglucosamine 198:216 O-linked N-acetylglucosamine 189:216 O-linked N-acetylglucosamine (O-GlcNAc) 189:227 OBJECTIVE There is increasing evidence that the addition of O-linked N-acetylglucosamine (O-GlcNAc) to proteins plays an important role in cell signaling pathways. 24333294 13 24 theme hypertrophic 1859:1870 arg1 markers 1888:1894 hypertrophic differentiation markers 1859:1894 hypertrophic differentiation markers that have been observed in OA 1859:1924 The increase in O-GlcNAcylation could be responsible, at least partially, for the re-expression of hypertrophic differentiation markers that have been observed in OA. 24333294 10 25 dep cartilage 1444:1452 arg1 comparison 1422:1431 comparison 1422:1431 comparison 1422:1431 OA cartilage showed a re-distribution of the OGT and OGA isoforms, with a net increase in the presence of both enzymes, in comparison to healthy cartilage. 24333294 10 26 theme OA 1299:1300 arg1 cartilage 1302:1310 OA cartilage 1299:1310 OA cartilage 1299:1310 OA cartilage showed a re-distribution of the OGT and OGA isoforms, with a net increase in the presence of both enzymes, in comparison to healthy cartilage. 24333294 9 27 from increase 1242:1249 arg1 O-GlcNAcylation 1265:1279 the global O-GlcNAcylation 1254:1279 the global O-GlcNAcylation in the cartilage 1254:1296 RESULTS OA was associated with a 4-fold increase in the global O-GlcNAcylation in the cartilage. 24333294 0 28 theme N-acetylglucosamine 9:27 arg1 modification 48:59 O-linked N-acetylglucosamine (O-GlcNAc) protein modification 0:59 O-linked N-acetylglucosamine (O-GlcNAc) protein modification 0:59 O-linked N-acetylglucosamine (O-GlcNAc) protein modification is increased in the cartilage of patients with knee osteoarthritis. 24333294 6 29 theme age 914:916 arg1 donors 942:947 age and sex-matched healthy donors 914:947 age and sex-matched healthy donors 914:947 DESIGN Human cartilage was obtained from patients with knee OA and from age and sex-matched healthy donors. 24333294 10 30 theme enzymes 1410:1416 arg1 presence 1393:1400 the presence 1389:1400 the presence of both enzymes 1389:1416 OA cartilage showed a re-distribution of the OGT and OGA isoforms, with a net increase in the presence of both enzymes, in comparison to healthy cartilage. 24333294 5 31 with patients 720:727 arg1 OA 739:740 knee OA 734:740 knee OA 734:740 Our aim was to study whether O-GlcNAcylation and the enzymes responsible for this modification are dysregulated in the cartilage of patients with knee OA and whether interleukin-1 could induce these modifications in cultured human OA chondrocytes (HOC). 24333294 0 32 theme O-linked 0:7 arg1 O-GlcNAc 30:37 O-GlcNAc 30:37 O-GlcNAc 30:37 O-linked N-acetylglucosamine (O-GlcNAc) protein modification is increased in the cartilage of patients with knee osteoarthritis. 24333294 0 32 theme O-linked 0:7 arg1 N-acetylglucosamine 9:27 O-linked N-acetylglucosamine 0:27 O-linked N-acetylglucosamine (O-GlcNAc) protein modification 0:59 O-linked N-acetylglucosamine (O-GlcNAc) protein modification is increased in the cartilage of patients with knee osteoarthritis. 24333294 1 33 theme signaling 273:281 arg1 pathways 283:290 cell signaling pathways 268:290 cell signaling pathways 268:290 OBJECTIVE There is increasing evidence that the addition of O-linked N-acetylglucosamine (O-GlcNAc) to proteins plays an important role in cell signaling pathways. 24333294 12 34 theme responsible 1725:1735 arg1 enzymes 1717:1723 the enzymes 1713:1723 the enzymes responsible for this modification 1713:1757 CONCLUSIONS Our results indicate that a proinflammatory milieu could favor the accumulation of O-GlcNAcylated proteins in OA cartilage, together with the dysregulation of the enzymes responsible for this modification. 24333294 0 35 with patients 94:101 arg1 osteoarthritis 113:126 knee osteoarthritis 108:126 knee osteoarthritis 108:126 O-linked N-acetylglucosamine (O-GlcNAc) protein modification is increased in the cartilage of patients with knee osteoarthritis. 24333294 12 36 theme O-GlcNAcylated 1637:1650 arg1 proteins 1652:1659 O-GlcNAcylated proteins 1637:1659 O-GlcNAcylated proteins 1637:1659 CONCLUSIONS Our results indicate that a proinflammatory milieu could favor the accumulation of O-GlcNAcylated proteins in OA cartilage, together with the dysregulation of the enzymes responsible for this modification. 24333294 3 37 theme hypertrophic-like 458:474 arg1 changes 476:482 hypertrophic-like changes 458:482 hypertrophic-like changes in hyaline chondrocytes 458:506 Osteoarthritis (OA) is characterized by cartilage degradation, and hypertrophic-like changes in hyaline chondrocytes. 24333294 8 38 theme western 1188:1194 arg1 blot 1196:1199 western blot 1188:1199 western blot 1188:1199 Global protein O-GlcNAcylation and the synthesis of the key enzymes responsible for this modification, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), were assessed by western blot. 24333294 12 39 from accumulation 1621:1632 arg1 cartilage 1667:1675 OA cartilage 1664:1675 OA cartilage 1664:1675 CONCLUSIONS Our results indicate that a proinflammatory milieu could favor the accumulation of O-GlcNAcylated proteins in OA cartilage, together with the dysregulation of the enzymes responsible for this modification. 24333294 6 40 theme DESIGN 842:847 arg1 cartilage 855:863 DESIGN Human cartilage 842:863 DESIGN Human cartilage 842:863 DESIGN Human cartilage was obtained from patients with knee OA and from age and sex-matched healthy donors. 24333294 8 41 theme Global 1018:1023 arg1 O-GlcNAcylation 1033:1047 Global protein O-GlcNAcylation 1018:1047 Global protein O-GlcNAcylation 1018:1047 Global protein O-GlcNAcylation and the synthesis of the key enzymes responsible for this modification, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), were assessed by western blot. 24333294 1 42 theme N-acetylglucosamine 198:216 arg1 addition 177:184 the addition 173:184 the addition of O-linked N-acetylglucosamine (O-GlcNAc) to proteins 173:239 OBJECTIVE There is increasing evidence that the addition of O-linked N-acetylglucosamine (O-GlcNAc) to proteins plays an important role in cell signaling pathways. 24333294 8 43 theme O-GlcNAc 1121:1128 arg1 enzymes 1078:1084 the key enzymes 1070:1084 the key enzymes responsible for this modification 1070:1118 Global protein O-GlcNAcylation and the synthesis of the key enzymes responsible for this modification, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), were assessed by western blot. 24333294 8 43 theme O-GlcNAc 1121:1128 arg1 OGT 1143:1145 OGT 1143:1145 OGT 1143:1145 Global protein O-GlcNAcylation and the synthesis of the key enzymes responsible for this modification, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), were assessed by western blot. 24333294 8 43 theme O-GlcNAc 1121:1128 arg1 transferase 1130:1140 O-GlcNAc transferase 1121:1140 O-GlcNAc transferase (OGT) 1121:1146 Global protein O-GlcNAcylation and the synthesis of the key enzymes responsible for this modification, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), were assessed by western blot. 24333294 12 44 theme proteins 1652:1659 arg1 accumulation 1621:1632 the accumulation 1617:1632 the accumulation of O-GlcNAcylated proteins in OA cartilage 1617:1675 CONCLUSIONS Our results indicate that a proinflammatory milieu could favor the accumulation of O-GlcNAcylated proteins in OA cartilage, together with the dysregulation of the enzymes responsible for this modification. 24333294 7 45 theme catabolic 992:1000 arg1 IL-1α 1011:1015 the catabolic cytokine IL-1α 988:1015 the catabolic cytokine IL-1α 988:1015 HOC were cultured and stimulated with the catabolic cytokine IL-1α. 24333294 0 46 theme protein 40:46 arg1 modification 48:59 O-linked N-acetylglucosamine (O-GlcNAc) protein modification 0:59 O-linked N-acetylglucosamine (O-GlcNAc) protein modification 0:59 O-linked N-acetylglucosamine (O-GlcNAc) protein modification is increased in the cartilage of patients with knee osteoarthritis. 24333294 13 47 theme markers 1888:1894 arg1 re-expression 1842:1854 the re-expression 1838:1854 the re-expression of hypertrophic differentiation markers that have been observed in OA 1838:1924 The increase in O-GlcNAcylation could be responsible, at least partially, for the re-expression of hypertrophic differentiation markers that have been observed in OA. 24333294 1 48 theme O-linked 189:196 arg1 O-GlcNAc 219:226 O-GlcNAc 219:226 O-GlcNAc 219:226 OBJECTIVE There is increasing evidence that the addition of O-linked N-acetylglucosamine (O-GlcNAc) to proteins plays an important role in cell signaling pathways. 24333294 1 48 theme O-linked 189:196 arg1 N-acetylglucosamine 198:216 O-linked N-acetylglucosamine 189:216 O-linked N-acetylglucosamine (O-GlcNAc) 189:227 OBJECTIVE There is increasing evidence that the addition of O-linked N-acetylglucosamine (O-GlcNAc) to proteins plays an important role in cell signaling pathways. 24333294 3 49 theme hyaline 487:493 arg1 chondrocytes 495:506 hyaline chondrocytes 487:506 hyaline chondrocytes 487:506 Osteoarthritis (OA) is characterized by cartilage degradation, and hypertrophic-like changes in hyaline chondrocytes. 24333294 13 50 from increase 1764:1771 arg1 O-GlcNAcylation 1776:1790 O-GlcNAcylation 1776:1790 O-GlcNAcylation 1776:1790 The increase in O-GlcNAcylation could be responsible, at least partially, for the re-expression of hypertrophic differentiation markers that have been observed in OA. 24333294 10 51 theme isoforms 1356:1363 arg1 re-distribution 1321:1335 a re-distribution 1319:1335 a re-distribution of the OGT and OGA isoforms 1319:1363 OA cartilage showed a re-distribution of the OGT and OGA isoforms, with a net increase in the presence of both enzymes, in comparison to healthy cartilage. 24333294 6 52 with patients 883:890 arg1 OA 902:903 knee OA 897:903 knee OA 897:903 DESIGN Human cartilage was obtained from patients with knee OA and from age and sex-matched healthy donors. 24333294 5 53 theme patients 720:727 arg1 cartilage 707:715 the cartilage 703:715 the cartilage of patients with knee OA 703:740 Our aim was to study whether O-GlcNAcylation and the enzymes responsible for this modification are dysregulated in the cartilage of patients with knee OA and whether interleukin-1 could induce these modifications in cultured human OA chondrocytes (HOC). 24333294 6 54 theme knee 897:900 arg1 OA 902:903 knee OA 897:903 knee OA 897:903 DESIGN Human cartilage was obtained from patients with knee OA and from age and sex-matched healthy donors. 24333294 10 55 theme OGA 1352:1354 arg1 isoforms 1356:1363 the OGT and OGA isoforms 1340:1363 isoforms 1356:1363 OA cartilage showed a re-distribution of the OGT and OGA isoforms, with a net increase in the presence of both enzymes, in comparison to healthy cartilage. 24333294 2 56 theme hypertrophic 361:372 arg1 differentiation 374:388 hypertrophic differentiation 361:388 hypertrophic differentiation 361:388 In chondrocytes, accumulation of O-GlcNAc-modified proteins induces hypertrophic differentiation. 24333294 3 57 theme cartilage 431:439 arg1 degradation 441:451 cartilage degradation 431:451 cartilage degradation 431:451 Osteoarthritis (OA) is characterized by cartilage degradation, and hypertrophic-like changes in hyaline chondrocytes. 24333294 13 58 located observed 1911:1918 arg2 markers 1888:1894 hypertrophic differentiation markers 1859:1894 hypertrophic differentiation markers that have been observed in OA 1859:1924 The increase in O-GlcNAcylation could be responsible, at least partially, for the re-expression of hypertrophic differentiation markers that have been observed in OA. 24333294 13 58 located observed 1911:1918 arg1 OA 1923:1924 OA 1923:1924 OA 1923:1924 The increase in O-GlcNAcylation could be responsible, at least partially, for the re-expression of hypertrophic differentiation markers that have been observed in OA. 24333294 11 59 theme IL-1α 1463:1467 arg1 stimulation 1469:1479 IL-1α stimulation 1463:1479 IL-1α stimulation 1463:1479 In HOC, IL-1α stimulation rapidly increased O-GlcNAcylation and OGT and OGA synthesis. 24333294 10 60 from increase 1377:1384 arg1 presence 1393:1400 the presence 1389:1400 the presence of both enzymes 1389:1416 OA cartilage showed a re-distribution of the OGT and OGA isoforms, with a net increase in the presence of both enzymes, in comparison to healthy cartilage. 24333294 12 61 theme enzymes 1717:1723 arg1 dysregulation 1696:1708 the dysregulation 1692:1708 the dysregulation of the enzymes responsible for this modification 1692:1757 CONCLUSIONS Our results indicate that a proinflammatory milieu could favor the accumulation of O-GlcNAcylated proteins in OA cartilage, together with the dysregulation of the enzymes responsible for this modification. 24333294 9 62 theme 4-fold 1235:1240 arg1 increase 1242:1249 a 4-fold increase 1233:1249 a 4-fold increase in the global O-GlcNAcylation in the cartilage 1233:1296 RESULTS OA was associated with a 4-fold increase in the global O-GlcNAcylation in the cartilage. 24333294 5 63 dep induce 774:779 arg1 HOC 836:838 HOC 836:838 HOC 836:838 Our aim was to study whether O-GlcNAcylation and the enzymes responsible for this modification are dysregulated in the cartilage of patients with knee OA and whether interleukin-1 could induce these modifications in cultured human OA chondrocytes (HOC). 24333294 10 64 theme OGT 1344:1346 arg1 isoforms 1356:1363 the OGT and OGA isoforms 1340:1363 isoforms 1356:1363 OA cartilage showed a re-distribution of the OGT and OGA isoforms, with a net increase in the presence of both enzymes, in comparison to healthy cartilage. 24333294 2 65 theme proteins 344:351 arg1 accumulation 310:321 accumulation 310:321 accumulation of O-GlcNAc-modified proteins 310:351 In chondrocytes, accumulation of O-GlcNAc-modified proteins induces hypertrophic differentiation. 24333294 10 66 theme net 1373:1375 arg1 increase 1377:1384 a net increase 1371:1384 a net increase in the presence of both enzymes 1371:1416 OA cartilage showed a re-distribution of the OGT and OGA isoforms, with a net increase in the presence of both enzymes, in comparison to healthy cartilage. 24333294 2 67 theme O-GlcNAc-modified 326:342 arg1 proteins 344:351 O-GlcNAc-modified proteins 326:351 O-GlcNAc-modified proteins 326:351 In chondrocytes, accumulation of O-GlcNAc-modified proteins induces hypertrophic differentiation. 24333294 12 68 theme proinflammatory 1582:1596 arg1 milieu 1598:1603 a proinflammatory milieu 1580:1603 a proinflammatory milieu 1580:1603 CONCLUSIONS Our results indicate that a proinflammatory milieu could favor the accumulation of O-GlcNAcylated proteins in OA cartilage, together with the dysregulation of the enzymes responsible for this modification. 24333294 5 69 theme cultured 804:811 arg1 chondrocytes 822:833 cultured human OA chondrocytes 804:833 cultured human OA chondrocytes 804:833 Our aim was to study whether O-GlcNAcylation and the enzymes responsible for this modification are dysregulated in the cartilage of patients with knee OA and whether interleukin-1 could induce these modifications in cultured human OA chondrocytes (HOC). 24333294 12 70 dep CONCLUSIONS 1542:1552 arg1 indicate 1566:1573 indicate 1566:1573 indicate that a proinflammatory milieu could favor the accumulation of O-GlcNAcylated proteins in OA cartilage, together with the dysregulation of the enzymes responsible for this modification 1566:1757 CONCLUSIONS Our results indicate that a proinflammatory milieu could favor the accumulation of O-GlcNAcylated proteins in OA cartilage, together with the dysregulation of the enzymes responsible for this modification. 24333294 8 71 theme protein 1025:1031 arg1 O-GlcNAcylation 1033:1047 Global protein O-GlcNAcylation 1018:1047 Global protein O-GlcNAcylation 1018:1047 Global protein O-GlcNAcylation and the synthesis of the key enzymes responsible for this modification, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), were assessed by western blot. 24333294 5 72 theme human 813:817 arg1 chondrocytes 822:833 cultured human OA chondrocytes 804:833 cultured human OA chondrocytes 804:833 Our aim was to study whether O-GlcNAcylation and the enzymes responsible for this modification are dysregulated in the cartilage of patients with knee OA and whether interleukin-1 could induce these modifications in cultured human OA chondrocytes (HOC). 24333294 3 73 from changes 476:482 arg1 chondrocytes 495:506 hyaline chondrocytes 487:506 hyaline chondrocytes 487:506 Osteoarthritis (OA) is characterized by cartilage degradation, and hypertrophic-like changes in hyaline chondrocytes. 24333294 1 74 theme increasing 148:157 arg1 evidence 159:166 increasing evidence that the addition of O-linked N-acetylglucosamine (O-GlcNAc) to proteins plays an important role in cell signaling pathways 148:290 increasing evidence that the addition of O-linked N-acetylglucosamine (O-GlcNAc) to proteins plays an important role in cell signaling pathways 148:290 OBJECTIVE There is increasing evidence that the addition of O-linked N-acetylglucosamine (O-GlcNAc) to proteins plays an important role in cell signaling pathways. 24333294 11 75 theme OGA 1527:1529 arg1 synthesis 1531:1539 OGA synthesis 1527:1539 OGA synthesis 1527:1539 In HOC, IL-1α stimulation rapidly increased O-GlcNAcylation and OGT and OGA synthesis. 27806685 3 0 theme Agilent 860:866 arg1 chip 896:899 the Agilent 44 K Bovine (V2) Microarray chip 856:899 the Agilent 44 K Bovine (V2) Microarray chip 856:899 Liver samples were obtained at -7, 7, and 28 d relative to parturition and subsequent RNA was hybridized to the Agilent 44 K Bovine (V2) Microarray chip. 27806685 4 1 theme Impact 914:919 arg1 Approach 921:928 The Dynamic Impact Approach 902:928 The Dynamic Impact Approach 902:928 The Dynamic Impact Approach was used for pathway analysis, and Ingenuity Pathway Analysis was used for gene network analysis. 27806685 5 2 theme expressed 1073:1081 arg1 genes 1083:1087 differentially expressed genes 1058:1087 differentially expressed genes 1058:1087 RESULTS The greater number of differentially expressed genes in BCS4 cows in response to prepartum feed allowance (1071 vs 310, over the entire transition period) indicates that these animals were more responsive to prepartum nutrition management than optimally-conditioned cows. 27806685 12 3 theme condition 2437:2445 arg1 degree 2422:2427 optimal degree 2414:2427 optimal degree of body condition 2414:2445 CONCLUSION Overall, the data support the hypothesis that overfeeding in late-pregnancy should be limited to underconditioned cows, while cows with optimal degree of body condition should be maintained on an energy-restricted diet. 27806685 3 4 theme Microarray 885:894 arg1 chip 896:899 the Agilent 44 K Bovine (V2) Microarray chip 856:899 the Agilent 44 K Bovine (V2) Microarray chip 856:899 Liver samples were obtained at -7, 7, and 28 d relative to parturition and subsequent RNA was hybridized to the Agilent 44 K Bovine (V2) Microarray chip. 27806685 2 5 theme requirements 733:744 arg1 % 718:718 75 and 125 % 707:718 75 and 125 % of estimated requirements 707:744 METHODS Thirty-two mid-lactation grazing dairy cows of mixed age and breed were randomly allocated to one of four treatment groups in a 2 × 2 factorial arrangement: two prepartum BCS categories [4.0 (thin, BCS4) and 5.0 (optimal, BCS5); based on a 10-point scale], and two levels of energy intake during the 3 weeks preceding calving (75 and 125 % of estimated requirements). 27806685 2 5 theme requirements 733:744 arg1 requirements 733:744 estimated requirements 723:744 estimated requirements 723:744 METHODS Thirty-two mid-lactation grazing dairy cows of mixed age and breed were randomly allocated to one of four treatment groups in a 2 × 2 factorial arrangement: two prepartum BCS categories [4.0 (thin, BCS4) and 5.0 (optimal, BCS5); based on a 10-point scale], and two levels of energy intake during the 3 weeks preceding calving (75 and 125 % of estimated requirements). 27806685 3 6 theme V2 881:882 arg1 chip 896:899 the Agilent 44 K Bovine (V2) Microarray chip 856:899 the Agilent 44 K Bovine (V2) Microarray chip 856:899 Liver samples were obtained at -7, 7, and 28 d relative to parturition and subsequent RNA was hybridized to the Agilent 44 K Bovine (V2) Microarray chip. 27806685 8 7 theme amino 1748:1752 arg1 vitamin 1760:1766 amino acid, vitamin, and co-factor metabolism 1748:1792 vitamin 1760:1766 This is supported by opposite effects of prepartum feeding in BCS4 compared with BCS5 cows in pathways encompassing amino acid, vitamin, and co-factor metabolism. 27806685 5 8 theme nutrition 1254:1262 arg1 management 1264:1273 prepartum nutrition management 1244:1273 prepartum nutrition management 1244:1273 RESULTS The greater number of differentially expressed genes in BCS4 cows in response to prepartum feed allowance (1071 vs 310, over the entire transition period) indicates that these animals were more responsive to prepartum nutrition management than optimally-conditioned cows. 27806685 12 9 theme energy-restricted 2474:2490 arg1 diet 2492:2495 an energy-restricted diet 2471:2495 an energy-restricted diet 2471:2495 CONCLUSION Overall, the data support the hypothesis that overfeeding in late-pregnancy should be limited to underconditioned cows, while cows with optimal degree of body condition should be maintained on an energy-restricted diet. 27806685 5 10 dep allowance 1132:1140 arg1 1071 1143:1146 1071 1143:1146 1071 1143:1146 RESULTS The greater number of differentially expressed genes in BCS4 cows in response to prepartum feed allowance (1071 vs 310, over the entire transition period) indicates that these animals were more responsive to prepartum nutrition management than optimally-conditioned cows. 27806685 5 10 dep allowance 1132:1140 arg1 310 1151:1153 310 1151:1153 310 1151:1153 RESULTS The greater number of differentially expressed genes in BCS4 cows in response to prepartum feed allowance (1071 vs 310, over the entire transition period) indicates that these animals were more responsive to prepartum nutrition management than optimally-conditioned cows. 27806685 12 11 theme underconditioned 2375:2390 arg1 cows 2392:2395 underconditioned cows 2375:2395 underconditioned cows 2375:2395 CONCLUSION Overall, the data support the hypothesis that overfeeding in late-pregnancy should be limited to underconditioned cows, while cows with optimal degree of body condition should be maintained on an energy-restricted diet. 27806685 7 12 theme amino 1506:1510 arg1 metabolism 1517:1526 amino acid metabolism 1506:1526 amino acid metabolism 1506:1526 Altered carbohydrate and amino acid metabolism suggest a greater and more prolonged negative energy balance postpartum in BCS5 cows overfed prepartum. 27806685 2 13 theme BCS 551:553 arg1 categories 555:564 two prepartum BCS categories [4.0 (thin, BCS4) and 5.0 (optimal, BCS5); based on a 10-point scale] 537:634 two prepartum BCS categories [4.0 (thin, BCS4) and 5.0 (optimal, BCS5); based on a 10-point scale] 537:634 METHODS Thirty-two mid-lactation grazing dairy cows of mixed age and breed were randomly allocated to one of four treatment groups in a 2 × 2 factorial arrangement: two prepartum BCS categories [4.0 (thin, BCS4) and 5.0 (optimal, BCS5); based on a 10-point scale], and two levels of energy intake during the 3 weeks preceding calving (75 and 125 % of estimated requirements). 27806685 7 14 from cows 1608:1611 arg1 postpartum 1589:1598 postpartum 1589:1598 postpartum 1589:1598 Altered carbohydrate and amino acid metabolism suggest a greater and more prolonged negative energy balance postpartum in BCS5 cows overfed prepartum. 27806685 8 15 from effects 1662:1668 arg1 BCS4 1694:1697 BCS4 1694:1697 BCS4 1694:1697 This is supported by opposite effects of prepartum feeding in BCS4 compared with BCS5 cows in pathways encompassing amino acid, vitamin, and co-factor metabolism. 27806685 6 16 theme prepartal 1378:1386 arg1 level 1396:1400 prepartal feeding level 1378:1400 prepartal feeding level 1378:1400 However, independent of prepartum BCS, pathway analysis revealed that prepartal feeding level had a marked effect on carbohydrate, amino acid, lipid, and glycan metabolism. 27806685 1 17 theme potential 197:205 arg1 interactions 207:218 potential interactions 197:218 potential interactions between prepartum body condition score (BCS) and feeding management 197:286 BACKGROUND A transcriptomic approach was used to evaluate potential interactions between prepartum body condition score (BCS) and feeding management in the weeks before calving on hepatic metabolism during the periparturient period. 27806685 4 18 theme Pathway 975:981 arg1 Analysis 983:990 Ingenuity Pathway Analysis 965:990 Ingenuity Pathway Analysis 965:990 The Dynamic Impact Approach was used for pathway analysis, and Ingenuity Pathway Analysis was used for gene network analysis. 27806685 0 19 theme dairy 127:131 arg1 cows 133:136 grazing dairy cows 119:136 grazing dairy cows 119:136 Prepartum body condition score and plane of nutrition affect the hepatic transcriptome during the transition period in grazing dairy cows. 27806685 4 20 theme Dynamic 906:912 arg1 Approach 921:928 The Dynamic Impact Approach 902:928 The Dynamic Impact Approach 902:928 The Dynamic Impact Approach was used for pathway analysis, and Ingenuity Pathway Analysis was used for gene network analysis. 27806685 8 21 theme BCS5 1713:1716 arg1 cows 1718:1721 BCS5 cows 1713:1721 BCS5 cows in pathways encompassing amino acid, vitamin, and co-factor metabolism 1713:1792 This is supported by opposite effects of prepartum feeding in BCS4 compared with BCS5 cows in pathways encompassing amino acid, vitamin, and co-factor metabolism. 27806685 2 22 from groups 496:501 arg1 arrangement 524:534 a 2 × 2 factorial arrangement 506:534 a 2 × 2 factorial arrangement 506:534 METHODS Thirty-two mid-lactation grazing dairy cows of mixed age and breed were randomly allocated to one of four treatment groups in a 2 × 2 factorial arrangement: two prepartum BCS categories [4.0 (thin, BCS4) and 5.0 (optimal, BCS5); based on a 10-point scale], and two levels of energy intake during the 3 weeks preceding calving (75 and 125 % of estimated requirements). 27806685 9 23 theme metabolic 1842:1850 arg1 adaptation 1852:1861 the metabolic adaptation 1838:1861 the metabolic adaptation to the onset of lactation in BCS5 cows 1838:1900 The prepartum feed restriction ameliorates the metabolic adaptation to the onset of lactation in BCS5 cows, while detrimentally affecting BCS4 cows, which seem to better adapt when overfed. 27806685 5 24 from cows 1097:1100 arg1 response 1105:1112 response 1105:1112 response to prepartum feed allowance (1071 vs 310, over the entire transition period) 1105:1189 RESULTS The greater number of differentially expressed genes in BCS4 cows in response to prepartum feed allowance (1071 vs 310, over the entire transition period) indicates that these animals were more responsive to prepartum nutrition management than optimally-conditioned cows. 27806685 6 25 theme amino 1439:1443 arg1 acid 1445:1448 amino acid 1439:1448 amino acid 1439:1448 However, independent of prepartum BCS, pathway analysis revealed that prepartal feeding level had a marked effect on carbohydrate, amino acid, lipid, and glycan metabolism. 27806685 11 26 theme thin 2222:2225 arg1 cows 2227:2230 feed-restricted thin cows 2206:2230 feed-restricted thin cows 2206:2230 Furthermore, IPA network analysis suggests liver damage in feed-restricted thin cows, likely due to metabolic overload. 27806685 4 27 theme network 1010:1016 arg1 analysis 1018:1025 gene network analysis 1005:1025 gene network analysis 1005:1025 The Dynamic Impact Approach was used for pathway analysis, and Ingenuity Pathway Analysis was used for gene network analysis. 27806685 1 28 theme hepatic 319:325 arg1 metabolism 327:336 hepatic metabolism 319:336 hepatic metabolism 319:336 BACKGROUND A transcriptomic approach was used to evaluate potential interactions between prepartum body condition score (BCS) and feeding management in the weeks before calving on hepatic metabolism during the periparturient period. 27806685 2 29 theme treatment 486:494 arg1 groups 496:501 four treatment groups 481:501 four treatment groups in a 2 × 2 factorial arrangement 481:534 METHODS Thirty-two mid-lactation grazing dairy cows of mixed age and breed were randomly allocated to one of four treatment groups in a 2 × 2 factorial arrangement: two prepartum BCS categories [4.0 (thin, BCS4) and 5.0 (optimal, BCS5); based on a 10-point scale], and two levels of energy intake during the 3 weeks preceding calving (75 and 125 % of estimated requirements). 27806685 5 30 theme prepartum 1117:1125 arg1 allowance 1132:1140 prepartum feed allowance 1117:1140 prepartum feed allowance (1071 vs 310, over the entire transition period) 1117:1189 RESULTS The greater number of differentially expressed genes in BCS4 cows in response to prepartum feed allowance (1071 vs 310, over the entire transition period) indicates that these animals were more responsive to prepartum nutrition management than optimally-conditioned cows. 27806685 0 31 theme hepatic 65:71 arg1 transcriptome 73:85 the hepatic transcriptome 61:85 the hepatic transcriptome during the transition period in grazing dairy cows 61:136 Prepartum body condition score and plane of nutrition affect the hepatic transcriptome during the transition period in grazing dairy cows. 27806685 2 32 dep allocated 461:469 arg1 categories 555:564 two prepartum BCS categories [4.0 (thin, BCS4) and 5.0 (optimal, BCS5); based on a 10-point scale] 537:634 two prepartum BCS categories [4.0 (thin, BCS4) and 5.0 (optimal, BCS5); based on a 10-point scale] 537:634 METHODS Thirty-two mid-lactation grazing dairy cows of mixed age and breed were randomly allocated to one of four treatment groups in a 2 × 2 factorial arrangement: two prepartum BCS categories [4.0 (thin, BCS4) and 5.0 (optimal, BCS5); based on a 10-point scale], and two levels of energy intake during the 3 weeks preceding calving (75 and 125 % of estimated requirements). 27806685 2 32 dep allocated 461:469 arg1 levels 645:650 two levels 641:650 two levels of energy intake during the 3 weeks preceding calving (75 and 125 % of estimated requirements) 641:745 METHODS Thirty-two mid-lactation grazing dairy cows of mixed age and breed were randomly allocated to one of four treatment groups in a 2 × 2 factorial arrangement: two prepartum BCS categories [4.0 (thin, BCS4) and 5.0 (optimal, BCS5); based on a 10-point scale], and two levels of energy intake during the 3 weeks preceding calving (75 and 125 % of estimated requirements). 27806685 8 33 theme prepartum 1673:1681 arg1 feeding 1683:1689 prepartum feeding 1673:1689 prepartum feeding in BCS4 compared with BCS5 cows in pathways encompassing amino acid, vitamin, and co-factor metabolism 1673:1792 This is supported by opposite effects of prepartum feeding in BCS4 compared with BCS5 cows in pathways encompassing amino acid, vitamin, and co-factor metabolism. 27806685 1 34 theme transcriptomic 152:165 arg1 approach 167:174 A transcriptomic approach 150:174 A transcriptomic approach 150:174 BACKGROUND A transcriptomic approach was used to evaluate potential interactions between prepartum body condition score (BCS) and feeding management in the weeks before calving on hepatic metabolism during the periparturient period. 27806685 7 35 theme negative 1565:1572 arg1 balance 1581:1587 a greater and more prolonged negative energy balance 1536:1587 a greater and more prolonged negative energy balance postpartum in BCS5 cows overfed prepartum 1536:1629 Altered carbohydrate and amino acid metabolism suggest a greater and more prolonged negative energy balance postpartum in BCS5 cows overfed prepartum. 27806685 9 36 theme lactation 1879:1887 arg1 onset 1870:1874 the onset 1866:1874 the onset of lactation 1866:1887 The prepartum feed restriction ameliorates the metabolic adaptation to the onset of lactation in BCS5 cows, while detrimentally affecting BCS4 cows, which seem to better adapt when overfed. 27806685 10 37 theme better 2071:2076 arg1 status 2093:2098 better hepatic health status 2071:2098 better hepatic health status 2071:2098 Alterations in the glycosaminoglycans synthesis pathway support this idea, indicating better hepatic health status in feed-restricted BCS5 and overfed BCS4 cows. 27806685 1 38 theme periparturient 349:362 arg1 period 364:369 the periparturient period 345:369 the periparturient period 345:369 BACKGROUND A transcriptomic approach was used to evaluate potential interactions between prepartum body condition score (BCS) and feeding management in the weeks before calving on hepatic metabolism during the periparturient period. 27806685 2 39 theme 2 × 2 508:512 arg1 arrangement 524:534 a 2 × 2 factorial arrangement 506:534 a 2 × 2 factorial arrangement 506:534 METHODS Thirty-two mid-lactation grazing dairy cows of mixed age and breed were randomly allocated to one of four treatment groups in a 2 × 2 factorial arrangement: two prepartum BCS categories [4.0 (thin, BCS4) and 5.0 (optimal, BCS5); based on a 10-point scale], and two levels of energy intake during the 3 weeks preceding calving (75 and 125 % of estimated requirements). 27806685 5 40 dep RESULTS 1028:1034 arg1 indicates 1191:1199 indicates 1191:1199 indicates that these animals were more responsive to prepartum nutrition management than optimally-conditioned cows 1191:1305 RESULTS The greater number of differentially expressed genes in BCS4 cows in response to prepartum feed allowance (1071 vs 310, over the entire transition period) indicates that these animals were more responsive to prepartum nutrition management than optimally-conditioned cows. 27806685 9 41 theme BCS5 1892:1895 arg1 cows 1897:1900 BCS5 cows 1892:1900 BCS5 cows 1892:1900 The prepartum feed restriction ameliorates the metabolic adaptation to the onset of lactation in BCS5 cows, while detrimentally affecting BCS4 cows, which seem to better adapt when overfed. 27806685 2 42 dep METHODS 372:378 arg1 cows 419:422 Thirty-two mid-lactation grazing dairy cows 380:422 METHODS Thirty-two mid-lactation grazing dairy cows of mixed age and breed 372:445 METHODS Thirty-two mid-lactation grazing dairy cows of mixed age and breed were randomly allocated to one of four treatment groups in a 2 × 2 factorial arrangement: two prepartum BCS categories [4.0 (thin, BCS4) and 5.0 (optimal, BCS5); based on a 10-point scale], and two levels of energy intake during the 3 weeks preceding calving (75 and 125 % of estimated requirements). 27806685 2 43 theme dairy 413:417 arg1 cows 419:422 Thirty-two mid-lactation grazing dairy cows 380:422 METHODS Thirty-two mid-lactation grazing dairy cows of mixed age and breed 372:445 METHODS Thirty-two mid-lactation grazing dairy cows of mixed age and breed were randomly allocated to one of four treatment groups in a 2 × 2 factorial arrangement: two prepartum BCS categories [4.0 (thin, BCS4) and 5.0 (optimal, BCS5); based on a 10-point scale], and two levels of energy intake during the 3 weeks preceding calving (75 and 125 % of estimated requirements). 27806685 0 44 theme transition 98:107 arg1 period 109:114 the transition period 94:114 the transition period 94:114 Prepartum body condition score and plane of nutrition affect the hepatic transcriptome during the transition period in grazing dairy cows. 27806685 7 45 theme greater 1538:1544 arg1 balance 1581:1587 a greater and more prolonged negative energy balance 1536:1587 a greater and more prolonged negative energy balance postpartum in BCS5 cows overfed prepartum 1536:1629 Altered carbohydrate and amino acid metabolism suggest a greater and more prolonged negative energy balance postpartum in BCS5 cows overfed prepartum. 27806685 2 46 theme 10-point 620:627 arg1 scale 629:633 a 10-point scale 618:633 a 10-point scale 618:633 METHODS Thirty-two mid-lactation grazing dairy cows of mixed age and breed were randomly allocated to one of four treatment groups in a 2 × 2 factorial arrangement: two prepartum BCS categories [4.0 (thin, BCS4) and 5.0 (optimal, BCS5); based on a 10-point scale], and two levels of energy intake during the 3 weeks preceding calving (75 and 125 % of estimated requirements). 27806685 2 47 theme mid-lactation 391:403 arg1 cows 419:422 Thirty-two mid-lactation grazing dairy cows 380:422 METHODS Thirty-two mid-lactation grazing dairy cows of mixed age and breed 372:445 METHODS Thirty-two mid-lactation grazing dairy cows of mixed age and breed were randomly allocated to one of four treatment groups in a 2 × 2 factorial arrangement: two prepartum BCS categories [4.0 (thin, BCS4) and 5.0 (optimal, BCS5); based on a 10-point scale], and two levels of energy intake during the 3 weeks preceding calving (75 and 125 % of estimated requirements). 27806685 0 48 theme Prepartum 0:8 arg1 score 25:29 Prepartum body condition score 0:29 Prepartum body condition score 0:29 Prepartum body condition score and plane of nutrition affect the hepatic transcriptome during the transition period in grazing dairy cows. 27806685 1 49 theme feeding 269:275 arg1 management 277:286 feeding management 269:286 feeding management 269:286 BACKGROUND A transcriptomic approach was used to evaluate potential interactions between prepartum body condition score (BCS) and feeding management in the weeks before calving on hepatic metabolism during the periparturient period. 27806685 6 50 theme glycan 1462:1467 arg1 metabolism 1469:1478 glycan metabolism 1462:1478 glycan metabolism 1462:1478 However, independent of prepartum BCS, pathway analysis revealed that prepartal feeding level had a marked effect on carbohydrate, amino acid, lipid, and glycan metabolism. 27806685 4 51 used used 934:937 arg2 Approach 921:928 The Dynamic Impact Approach 902:928 The Dynamic Impact Approach 902:928 The Dynamic Impact Approach was used for pathway analysis, and Ingenuity Pathway Analysis was used for gene network analysis. 27806685 2 52 theme breed 441:445 arg1 cows 419:422 Thirty-two mid-lactation grazing dairy cows 380:422 METHODS Thirty-two mid-lactation grazing dairy cows of mixed age and breed 372:445 METHODS Thirty-two mid-lactation grazing dairy cows of mixed age and breed were randomly allocated to one of four treatment groups in a 2 × 2 factorial arrangement: two prepartum BCS categories [4.0 (thin, BCS4) and 5.0 (optimal, BCS5); based on a 10-point scale], and two levels of energy intake during the 3 weeks preceding calving (75 and 125 % of estimated requirements). 27806685 10 53 theme feed-restricted 2103:2117 arg1 BCS5 2119:2122 feed-restricted BCS5 2103:2122 feed-restricted BCS5 2103:2122 Alterations in the glycosaminoglycans synthesis pathway support this idea, indicating better hepatic health status in feed-restricted BCS5 and overfed BCS4 cows. 27806685 2 54 theme age 433:435 arg1 cows 419:422 Thirty-two mid-lactation grazing dairy cows 380:422 METHODS Thirty-two mid-lactation grazing dairy cows of mixed age and breed 372:445 METHODS Thirty-two mid-lactation grazing dairy cows of mixed age and breed were randomly allocated to one of four treatment groups in a 2 × 2 factorial arrangement: two prepartum BCS categories [4.0 (thin, BCS4) and 5.0 (optimal, BCS5); based on a 10-point scale], and two levels of energy intake during the 3 weeks preceding calving (75 and 125 % of estimated requirements). 27806685 0 55 theme condition 15:23 arg1 score 25:29 Prepartum body condition score 0:29 Prepartum body condition score 0:29 Prepartum body condition score and plane of nutrition affect the hepatic transcriptome during the transition period in grazing dairy cows. 27806685 7 56 theme acid 1512:1515 arg1 metabolism 1517:1526 amino acid metabolism 1506:1526 amino acid metabolism 1506:1526 Altered carbohydrate and amino acid metabolism suggest a greater and more prolonged negative energy balance postpartum in BCS5 cows overfed prepartum. 27806685 8 57 from cows 1718:1721 arg1 pathways 1726:1733 pathways 1726:1733 pathways encompassing amino acid, vitamin, and co-factor metabolism 1726:1792 This is supported by opposite effects of prepartum feeding in BCS4 compared with BCS5 cows in pathways encompassing amino acid, vitamin, and co-factor metabolism. 27806685 9 58 theme BCS4 1933:1936 arg1 cows 1938:1941 BCS4 cows 1933:1941 BCS4 cows 1933:1941 The prepartum feed restriction ameliorates the metabolic adaptation to the onset of lactation in BCS5 cows, while detrimentally affecting BCS4 cows, which seem to better adapt when overfed. 27806685 5 59 theme entire 1165:1170 arg1 period 1183:1188 the entire transition period 1161:1188 the entire transition period 1161:1188 RESULTS The greater number of differentially expressed genes in BCS4 cows in response to prepartum feed allowance (1071 vs 310, over the entire transition period) indicates that these animals were more responsive to prepartum nutrition management than optimally-conditioned cows. 27806685 6 60 dep analysis 1355:1362 arg1 pathway 1347:1353 independent of prepartum BCS, pathway analysis 1317:1362 pathway 1347:1353 However, independent of prepartum BCS, pathway analysis revealed that prepartal feeding level had a marked effect on carbohydrate, amino acid, lipid, and glycan metabolism. 27806685 4 61 used used 996:999 arg2 Analysis 983:990 Ingenuity Pathway Analysis 965:990 Ingenuity Pathway Analysis 965:990 The Dynamic Impact Approach was used for pathway analysis, and Ingenuity Pathway Analysis was used for gene network analysis. 27806685 4 62 theme pathway 943:949 arg1 analysis 951:958 pathway analysis 943:958 pathway analysis 943:958 The Dynamic Impact Approach was used for pathway analysis, and Ingenuity Pathway Analysis was used for gene network analysis. 27806685 5 63 theme prepartum 1244:1252 arg1 management 1264:1273 prepartum nutrition management 1244:1273 prepartum nutrition management 1244:1273 RESULTS The greater number of differentially expressed genes in BCS4 cows in response to prepartum feed allowance (1071 vs 310, over the entire transition period) indicates that these animals were more responsive to prepartum nutrition management than optimally-conditioned cows. 27806685 1 64 theme prepartum 228:236 arg1 BCS 260:262 BCS 260:262 BCS 260:262 BACKGROUND A transcriptomic approach was used to evaluate potential interactions between prepartum body condition score (BCS) and feeding management in the weeks before calving on hepatic metabolism during the periparturient period. 27806685 1 64 theme prepartum 228:236 arg1 score 253:257 prepartum body condition score 228:257 prepartum body condition score (BCS) 228:263 BACKGROUND A transcriptomic approach was used to evaluate potential interactions between prepartum body condition score (BCS) and feeding management in the weeks before calving on hepatic metabolism during the periparturient period. 27806685 3 65 theme 44 K 868:871 arg1 chip 896:899 the Agilent 44 K Bovine (V2) Microarray chip 856:899 the Agilent 44 K Bovine (V2) Microarray chip 856:899 Liver samples were obtained at -7, 7, and 28 d relative to parturition and subsequent RNA was hybridized to the Agilent 44 K Bovine (V2) Microarray chip. 27806685 2 66 theme energy 655:660 arg1 intake 662:667 energy intake 655:667 energy intake during the 3 weeks preceding calving (75 and 125 % of estimated requirements) 655:745 METHODS Thirty-two mid-lactation grazing dairy cows of mixed age and breed were randomly allocated to one of four treatment groups in a 2 × 2 factorial arrangement: two prepartum BCS categories [4.0 (thin, BCS4) and 5.0 (optimal, BCS5); based on a 10-point scale], and two levels of energy intake during the 3 weeks preceding calving (75 and 125 % of estimated requirements). 27806685 12 67 theme body 2432:2435 arg1 condition 2437:2445 body condition 2432:2445 body condition 2432:2445 CONCLUSION Overall, the data support the hypothesis that overfeeding in late-pregnancy should be limited to underconditioned cows, while cows with optimal degree of body condition should be maintained on an energy-restricted diet. 27806685 11 68 theme IPA 2160:2162 arg1 analysis 2172:2179 IPA network analysis 2160:2179 IPA network analysis 2160:2179 Furthermore, IPA network analysis suggests liver damage in feed-restricted thin cows, likely due to metabolic overload. 27806685 1 69 theme condition 243:251 arg1 BCS 260:262 BCS 260:262 BCS 260:262 BACKGROUND A transcriptomic approach was used to evaluate potential interactions between prepartum body condition score (BCS) and feeding management in the weeks before calving on hepatic metabolism during the periparturient period. 27806685 1 69 theme condition 243:251 arg1 score 253:257 prepartum body condition score 228:257 prepartum body condition score (BCS) 228:263 BACKGROUND A transcriptomic approach was used to evaluate potential interactions between prepartum body condition score (BCS) and feeding management in the weeks before calving on hepatic metabolism during the periparturient period. 27806685 2 70 dep categories 555:564 arg1 [4.0 566:569 [4.0 566:569 [4.0 566:569 METHODS Thirty-two mid-lactation grazing dairy cows of mixed age and breed were randomly allocated to one of four treatment groups in a 2 × 2 factorial arrangement: two prepartum BCS categories [4.0 (thin, BCS4) and 5.0 (optimal, BCS5); based on a 10-point scale], and two levels of energy intake during the 3 weeks preceding calving (75 and 125 % of estimated requirements). 27806685 2 70 dep categories 555:564 arg1 5.0 588:590 5.0 588:590 5.0 588:590 METHODS Thirty-two mid-lactation grazing dairy cows of mixed age and breed were randomly allocated to one of four treatment groups in a 2 × 2 factorial arrangement: two prepartum BCS categories [4.0 (thin, BCS4) and 5.0 (optimal, BCS5); based on a 10-point scale], and two levels of energy intake during the 3 weeks preceding calving (75 and 125 % of estimated requirements). 27806685 6 71 theme prepartum 1332:1340 arg1 BCS 1342:1344 prepartum BCS 1332:1344 prepartum BCS 1332:1344 However, independent of prepartum BCS, pathway analysis revealed that prepartal feeding level had a marked effect on carbohydrate, amino acid, lipid, and glycan metabolism. 27806685 11 72 theme feed-restricted 2206:2220 arg1 cows 2227:2230 feed-restricted thin cows 2206:2230 feed-restricted thin cows 2206:2230 Furthermore, IPA network analysis suggests liver damage in feed-restricted thin cows, likely due to metabolic overload. 27806685 6 73 theme independent 1317:1327 arg1 analysis 1355:1362 independent of prepartum BCS, pathway analysis 1317:1362 analysis 1355:1362 However, independent of prepartum BCS, pathway analysis revealed that prepartal feeding level had a marked effect on carbohydrate, amino acid, lipid, and glycan metabolism. 27806685 5 74 theme genes 1083:1087 arg1 number 1048:1053 The greater number 1036:1053 The greater number of differentially expressed genes in BCS4 cows in response to prepartum feed allowance (1071 vs 310, over the entire transition period) 1036:1189 RESULTS The greater number of differentially expressed genes in BCS4 cows in response to prepartum feed allowance (1071 vs 310, over the entire transition period) indicates that these animals were more responsive to prepartum nutrition management than optimally-conditioned cows. 27806685 10 75 theme BCS4 2136:2139 arg1 cows 2141:2144 overfed BCS4 cows 2128:2144 overfed BCS4 cows 2128:2144 Alterations in the glycosaminoglycans synthesis pathway support this idea, indicating better hepatic health status in feed-restricted BCS5 and overfed BCS4 cows. 27806685 5 76 from number 1048:1053 arg1 cows 1097:1100 BCS4 cows 1092:1100 BCS4 cows in response to prepartum feed allowance (1071 vs 310, over the entire transition period) 1092:1189 RESULTS The greater number of differentially expressed genes in BCS4 cows in response to prepartum feed allowance (1071 vs 310, over the entire transition period) indicates that these animals were more responsive to prepartum nutrition management than optimally-conditioned cows. 27806685 6 77 theme marked 1408:1413 arg1 effect 1415:1420 a marked effect 1406:1420 a marked effect 1406:1420 However, independent of prepartum BCS, pathway analysis revealed that prepartal feeding level had a marked effect on carbohydrate, amino acid, lipid, and glycan metabolism. 27806685 11 78 theme network 2164:2170 arg1 analysis 2172:2179 IPA network analysis 2160:2179 IPA network analysis 2160:2179 Furthermore, IPA network analysis suggests liver damage in feed-restricted thin cows, likely due to metabolic overload. 27806685 2 79 theme optimal 593:599 arg1 BCS5 602:605 optimal, BCS5); 593:607 BCS5 602:605 METHODS Thirty-two mid-lactation grazing dairy cows of mixed age and breed were randomly allocated to one of four treatment groups in a 2 × 2 factorial arrangement: two prepartum BCS categories [4.0 (thin, BCS4) and 5.0 (optimal, BCS5); based on a 10-point scale], and two levels of energy intake during the 3 weeks preceding calving (75 and 125 % of estimated requirements). 27806685 7 80 from postpartum 1589:1598 arg1 cows 1608:1611 BCS5 cows 1603:1611 BCS5 cows overfed prepartum 1603:1629 Altered carbohydrate and amino acid metabolism suggest a greater and more prolonged negative energy balance postpartum in BCS5 cows overfed prepartum. 27806685 4 81 theme gene 1005:1008 arg1 analysis 1018:1025 gene network analysis 1005:1025 gene network analysis 1005:1025 The Dynamic Impact Approach was used for pathway analysis, and Ingenuity Pathway Analysis was used for gene network analysis. 27806685 2 82 dep 5.0 588:590 arg1 BCS5 602:605 optimal, BCS5); 593:607 BCS5 602:605 METHODS Thirty-two mid-lactation grazing dairy cows of mixed age and breed were randomly allocated to one of four treatment groups in a 2 × 2 factorial arrangement: two prepartum BCS categories [4.0 (thin, BCS4) and 5.0 (optimal, BCS5); based on a 10-point scale], and two levels of energy intake during the 3 weeks preceding calving (75 and 125 % of estimated requirements). 27806685 12 83 with cows 2404:2407 arg1 degree 2422:2427 optimal degree 2414:2427 optimal degree of body condition 2414:2445 CONCLUSION Overall, the data support the hypothesis that overfeeding in late-pregnancy should be limited to underconditioned cows, while cows with optimal degree of body condition should be maintained on an energy-restricted diet. 27806685 4 84 theme Ingenuity 965:973 arg1 Analysis 983:990 Ingenuity Pathway Analysis 965:990 Ingenuity Pathway Analysis 965:990 The Dynamic Impact Approach was used for pathway analysis, and Ingenuity Pathway Analysis was used for gene network analysis. 27806685 0 85 theme grazing 119:125 arg1 cows 133:136 grazing dairy cows 119:136 grazing dairy cows 119:136 Prepartum body condition score and plane of nutrition affect the hepatic transcriptome during the transition period in grazing dairy cows. 27806685 5 86 theme optimally-conditioned 1280:1300 arg1 cows 1302:1305 optimally-conditioned cows 1280:1305 optimally-conditioned cows 1280:1305 RESULTS The greater number of differentially expressed genes in BCS4 cows in response to prepartum feed allowance (1071 vs 310, over the entire transition period) indicates that these animals were more responsive to prepartum nutrition management than optimally-conditioned cows. 27806685 11 87 from damage 2196:2201 arg1 cows 2227:2230 feed-restricted thin cows 2206:2230 feed-restricted thin cows 2206:2230 Furthermore, IPA network analysis suggests liver damage in feed-restricted thin cows, likely due to metabolic overload. 27806685 6 88 theme feeding 1388:1394 arg1 level 1396:1400 prepartal feeding level 1378:1400 prepartal feeding level 1378:1400 However, independent of prepartum BCS, pathway analysis revealed that prepartal feeding level had a marked effect on carbohydrate, amino acid, lipid, and glycan metabolism. 27806685 7 89 theme Altered 1481:1487 arg1 carbohydrate 1489:1500 Altered carbohydrate 1481:1500 Altered carbohydrate 1481:1500 Altered carbohydrate and amino acid metabolism suggest a greater and more prolonged negative energy balance postpartum in BCS5 cows overfed prepartum. 27806685 2 90 theme prepartum 541:549 arg1 categories 555:564 two prepartum BCS categories [4.0 (thin, BCS4) and 5.0 (optimal, BCS5); based on a 10-point scale] 537:634 two prepartum BCS categories [4.0 (thin, BCS4) and 5.0 (optimal, BCS5); based on a 10-point scale] 537:634 METHODS Thirty-two mid-lactation grazing dairy cows of mixed age and breed were randomly allocated to one of four treatment groups in a 2 × 2 factorial arrangement: two prepartum BCS categories [4.0 (thin, BCS4) and 5.0 (optimal, BCS5); based on a 10-point scale], and two levels of energy intake during the 3 weeks preceding calving (75 and 125 % of estimated requirements). 27806685 0 91 from transcriptome 73:85 arg1 cows 133:136 grazing dairy cows 119:136 grazing dairy cows 119:136 Prepartum body condition score and plane of nutrition affect the hepatic transcriptome during the transition period in grazing dairy cows. 27806685 9 92 theme prepartum 1799:1807 arg1 restriction 1814:1824 The prepartum feed restriction 1795:1824 The prepartum feed restriction 1795:1824 The prepartum feed restriction ameliorates the metabolic adaptation to the onset of lactation in BCS5 cows, while detrimentally affecting BCS4 cows, which seem to better adapt when overfed. 27806685 10 93 theme glycosaminoglycans 2004:2021 arg1 pathway 2033:2039 the glycosaminoglycans synthesis pathway 2000:2039 the glycosaminoglycans synthesis pathway 2000:2039 Alterations in the glycosaminoglycans synthesis pathway support this idea, indicating better hepatic health status in feed-restricted BCS5 and overfed BCS4 cows. 27806685 2 94 theme estimated 723:731 arg1 requirements 733:744 estimated requirements 723:744 estimated requirements 723:744 METHODS Thirty-two mid-lactation grazing dairy cows of mixed age and breed were randomly allocated to one of four treatment groups in a 2 × 2 factorial arrangement: two prepartum BCS categories [4.0 (thin, BCS4) and 5.0 (optimal, BCS5); based on a 10-point scale], and two levels of energy intake during the 3 weeks preceding calving (75 and 125 % of estimated requirements). 27806685 12 95 from overfeeding 2324:2334 arg1 late-pregnancy 2339:2352 late-pregnancy 2339:2352 late-pregnancy 2339:2352 CONCLUSION Overall, the data support the hypothesis that overfeeding in late-pregnancy should be limited to underconditioned cows, while cows with optimal degree of body condition should be maintained on an energy-restricted diet. 27806685 8 96 from feeding 1683:1689 arg1 BCS4 1694:1697 BCS4 1694:1697 BCS4 1694:1697 This is supported by opposite effects of prepartum feeding in BCS4 compared with BCS5 cows in pathways encompassing amino acid, vitamin, and co-factor metabolism. 27806685 8 97 theme acid 1754:1757 arg1 vitamin 1760:1766 amino acid, vitamin, and co-factor metabolism 1748:1792 vitamin 1760:1766 This is supported by opposite effects of prepartum feeding in BCS4 compared with BCS5 cows in pathways encompassing amino acid, vitamin, and co-factor metabolism. 27806685 12 98 dep CONCLUSION 2267:2276 arg1 support 2296:2302 support 2296:2302 support the hypothesis that overfeeding in late-pregnancy should be limited to underconditioned cows, while cows with optimal degree of body condition should be maintained on an energy-restricted diet 2296:2495 CONCLUSION Overall, the data support the hypothesis that overfeeding in late-pregnancy should be limited to underconditioned cows, while cows with optimal degree of body condition should be maintained on an energy-restricted diet. 27806685 11 99 theme metabolic 2247:2255 arg1 overload 2257:2264 metabolic overload 2247:2264 metabolic overload 2247:2264 Furthermore, IPA network analysis suggests liver damage in feed-restricted thin cows, likely due to metabolic overload. 27806685 10 100 theme synthesis 2023:2031 arg1 pathway 2033:2039 the glycosaminoglycans synthesis pathway 2000:2039 the glycosaminoglycans synthesis pathway 2000:2039 Alterations in the glycosaminoglycans synthesis pathway support this idea, indicating better hepatic health status in feed-restricted BCS5 and overfed BCS4 cows. 27806685 1 101 used used 180:183 arg2 approach 167:174 A transcriptomic approach 150:174 A transcriptomic approach 150:174 BACKGROUND A transcriptomic approach was used to evaluate potential interactions between prepartum body condition score (BCS) and feeding management in the weeks before calving on hepatic metabolism during the periparturient period. 27806685 2 102 theme intake 662:667 arg1 levels 645:650 two levels 641:650 two levels of energy intake during the 3 weeks preceding calving (75 and 125 % of estimated requirements) 641:745 METHODS Thirty-two mid-lactation grazing dairy cows of mixed age and breed were randomly allocated to one of four treatment groups in a 2 × 2 factorial arrangement: two prepartum BCS categories [4.0 (thin, BCS4) and 5.0 (optimal, BCS5); based on a 10-point scale], and two levels of energy intake during the 3 weeks preceding calving (75 and 125 % of estimated requirements). 27806685 2 102 theme intake 662:667 arg1 categories 555:564 two prepartum BCS categories [4.0 (thin, BCS4) and 5.0 (optimal, BCS5); based on a 10-point scale] 537:634 two prepartum BCS categories [4.0 (thin, BCS4) and 5.0 (optimal, BCS5); based on a 10-point scale] 537:634 METHODS Thirty-two mid-lactation grazing dairy cows of mixed age and breed were randomly allocated to one of four treatment groups in a 2 × 2 factorial arrangement: two prepartum BCS categories [4.0 (thin, BCS4) and 5.0 (optimal, BCS5); based on a 10-point scale], and two levels of energy intake during the 3 weeks preceding calving (75 and 125 % of estimated requirements). 27806685 7 103 theme BCS5 1603:1606 arg1 cows 1608:1611 BCS5 cows 1603:1611 BCS5 cows overfed prepartum 1603:1629 Altered carbohydrate and amino acid metabolism suggest a greater and more prolonged negative energy balance postpartum in BCS5 cows overfed prepartum. 27806685 2 104 theme groups 496:501 arg1 groups 496:501 four treatment groups 481:501 four treatment groups in a 2 × 2 factorial arrangement 481:534 METHODS Thirty-two mid-lactation grazing dairy cows of mixed age and breed were randomly allocated to one of four treatment groups in a 2 × 2 factorial arrangement: two prepartum BCS categories [4.0 (thin, BCS4) and 5.0 (optimal, BCS5); based on a 10-point scale], and two levels of energy intake during the 3 weeks preceding calving (75 and 125 % of estimated requirements). 27806685 2 104 theme groups 496:501 arg1 one 474:476 one 474:476 one 474:476 METHODS Thirty-two mid-lactation grazing dairy cows of mixed age and breed were randomly allocated to one of four treatment groups in a 2 × 2 factorial arrangement: two prepartum BCS categories [4.0 (thin, BCS4) and 5.0 (optimal, BCS5); based on a 10-point scale], and two levels of energy intake during the 3 weeks preceding calving (75 and 125 % of estimated requirements). 27806685 5 105 theme BCS4 1092:1095 arg1 cows 1097:1100 BCS4 cows 1092:1100 BCS4 cows in response to prepartum feed allowance (1071 vs 310, over the entire transition period) 1092:1189 RESULTS The greater number of differentially expressed genes in BCS4 cows in response to prepartum feed allowance (1071 vs 310, over the entire transition period) indicates that these animals were more responsive to prepartum nutrition management than optimally-conditioned cows. 27806685 9 106 theme feed 1809:1812 arg1 restriction 1814:1824 The prepartum feed restriction 1795:1824 The prepartum feed restriction 1795:1824 The prepartum feed restriction ameliorates the metabolic adaptation to the onset of lactation in BCS5 cows, while detrimentally affecting BCS4 cows, which seem to better adapt when overfed. 27806685 6 107 contain had 1402:1404 arg2 effect 1415:1420 a marked effect 1406:1420 a marked effect 1406:1420 However, independent of prepartum BCS, pathway analysis revealed that prepartal feeding level had a marked effect on carbohydrate, amino acid, lipid, and glycan metabolism. 27806685 6 107 contain had 1402:1404 arg1 level 1396:1400 prepartal feeding level 1378:1400 prepartal feeding level 1378:1400 However, independent of prepartum BCS, pathway analysis revealed that prepartal feeding level had a marked effect on carbohydrate, amino acid, lipid, and glycan metabolism. 27806685 8 108 theme opposite 1653:1660 arg1 effects 1662:1668 opposite effects 1653:1668 opposite effects of prepartum feeding in BCS4 compared with BCS5 cows in pathways encompassing amino acid, vitamin, and co-factor metabolism 1653:1792 This is supported by opposite effects of prepartum feeding in BCS4 compared with BCS5 cows in pathways encompassing amino acid, vitamin, and co-factor metabolism. 27806685 7 109 theme postpartum 1589:1598 arg1 balance 1581:1587 a greater and more prolonged negative energy balance 1536:1587 a greater and more prolonged negative energy balance postpartum in BCS5 cows overfed prepartum 1536:1629 Altered carbohydrate and amino acid metabolism suggest a greater and more prolonged negative energy balance postpartum in BCS5 cows overfed prepartum. 27806685 8 110 from BCS4 1694:1697 arg1 effects 1662:1668 opposite effects 1653:1668 opposite effects of prepartum feeding in BCS4 compared with BCS5 cows in pathways encompassing amino acid, vitamin, and co-factor metabolism 1653:1792 This is supported by opposite effects of prepartum feeding in BCS4 compared with BCS5 cows in pathways encompassing amino acid, vitamin, and co-factor metabolism. 27806685 5 111 theme feed 1127:1130 arg1 allowance 1132:1140 prepartum feed allowance 1117:1140 prepartum feed allowance (1071 vs 310, over the entire transition period) 1117:1189 RESULTS The greater number of differentially expressed genes in BCS4 cows in response to prepartum feed allowance (1071 vs 310, over the entire transition period) indicates that these animals were more responsive to prepartum nutrition management than optimally-conditioned cows. 27806685 3 112 theme Liver 748:752 arg1 samples 754:760 Liver samples 748:760 Liver samples 748:760 Liver samples were obtained at -7, 7, and 28 d relative to parturition and subsequent RNA was hybridized to the Agilent 44 K Bovine (V2) Microarray chip. 27806685 7 113 theme energy 1574:1579 arg1 balance 1581:1587 a greater and more prolonged negative energy balance 1536:1587 a greater and more prolonged negative energy balance postpartum in BCS5 cows overfed prepartum 1536:1629 Altered carbohydrate and amino acid metabolism suggest a greater and more prolonged negative energy balance postpartum in BCS5 cows overfed prepartum. 27806685 2 114 theme factorial 514:522 arg1 arrangement 524:534 a 2 × 2 factorial arrangement 506:534 a 2 × 2 factorial arrangement 506:534 METHODS Thirty-two mid-lactation grazing dairy cows of mixed age and breed were randomly allocated to one of four treatment groups in a 2 × 2 factorial arrangement: two prepartum BCS categories [4.0 (thin, BCS4) and 5.0 (optimal, BCS5); based on a 10-point scale], and two levels of energy intake during the 3 weeks preceding calving (75 and 125 % of estimated requirements). 27806685 10 115 theme health 2086:2091 arg1 status 2093:2098 better hepatic health status 2071:2098 better hepatic health status 2071:2098 Alterations in the glycosaminoglycans synthesis pathway support this idea, indicating better hepatic health status in feed-restricted BCS5 and overfed BCS4 cows. 27806685 5 116 theme transition 1172:1181 arg1 period 1183:1188 the entire transition period 1161:1188 the entire transition period 1161:1188 RESULTS The greater number of differentially expressed genes in BCS4 cows in response to prepartum feed allowance (1071 vs 310, over the entire transition period) indicates that these animals were more responsive to prepartum nutrition management than optimally-conditioned cows. 27806685 8 117 theme feeding 1683:1689 arg1 effects 1662:1668 opposite effects 1653:1668 opposite effects of prepartum feeding in BCS4 compared with BCS5 cows in pathways encompassing amino acid, vitamin, and co-factor metabolism 1653:1792 This is supported by opposite effects of prepartum feeding in BCS4 compared with BCS5 cows in pathways encompassing amino acid, vitamin, and co-factor metabolism. 27806685 3 118 theme relative 795:802 arg1 d 793:793 -7, 7, and 28 d 779:793 -7, 7, and 28 d relative to parturition 779:817 Liver samples were obtained at -7, 7, and 28 d relative to parturition and subsequent RNA was hybridized to the Agilent 44 K Bovine (V2) Microarray chip. 27806685 10 119 theme overfed 2128:2134 arg1 cows 2141:2144 overfed BCS4 cows 2128:2144 overfed BCS4 cows 2128:2144 Alterations in the glycosaminoglycans synthesis pathway support this idea, indicating better hepatic health status in feed-restricted BCS5 and overfed BCS4 cows. 27806685 2 120 theme grazing 405:411 arg1 cows 419:422 Thirty-two mid-lactation grazing dairy cows 380:422 METHODS Thirty-two mid-lactation grazing dairy cows of mixed age and breed 372:445 METHODS Thirty-two mid-lactation grazing dairy cows of mixed age and breed were randomly allocated to one of four treatment groups in a 2 × 2 factorial arrangement: two prepartum BCS categories [4.0 (thin, BCS4) and 5.0 (optimal, BCS5); based on a 10-point scale], and two levels of energy intake during the 3 weeks preceding calving (75 and 125 % of estimated requirements). 27806685 0 121 theme body 10:13 arg1 score 25:29 Prepartum body condition score 0:29 Prepartum body condition score 0:29 Prepartum body condition score and plane of nutrition affect the hepatic transcriptome during the transition period in grazing dairy cows. 27806685 9 122 from adaptation 1852:1861 arg1 cows 1897:1900 BCS5 cows 1892:1900 BCS5 cows 1892:1900 The prepartum feed restriction ameliorates the metabolic adaptation to the onset of lactation in BCS5 cows, while detrimentally affecting BCS4 cows, which seem to better adapt when overfed. 27806685 5 123 theme greater 1040:1046 arg1 number 1048:1053 The greater number 1036:1053 The greater number of differentially expressed genes in BCS4 cows in response to prepartum feed allowance (1071 vs 310, over the entire transition period) 1036:1189 RESULTS The greater number of differentially expressed genes in BCS4 cows in response to prepartum feed allowance (1071 vs 310, over the entire transition period) indicates that these animals were more responsive to prepartum nutrition management than optimally-conditioned cows. 27806685 10 124 theme hepatic 2078:2084 arg1 status 2093:2098 better hepatic health status 2071:2098 better hepatic health status 2071:2098 Alterations in the glycosaminoglycans synthesis pathway support this idea, indicating better hepatic health status in feed-restricted BCS5 and overfed BCS4 cows. 27806685 3 125 theme subsequent 823:832 arg1 RNA 834:836 subsequent RNA 823:836 subsequent RNA 823:836 Liver samples were obtained at -7, 7, and 28 d relative to parturition and subsequent RNA was hybridized to the Agilent 44 K Bovine (V2) Microarray chip. 27806685 1 126 dep BACKGROUND 139:148 arg1 used 180:183 used 180:183 was used to evaluate potential interactions between prepartum body condition score (BCS) and feeding management in the weeks before calving on hepatic metabolism during the periparturient period 176:369 BACKGROUND A transcriptomic approach was used to evaluate potential interactions between prepartum body condition score (BCS) and feeding management in the weeks before calving on hepatic metabolism during the periparturient period. 27806685 2 127 theme mixed 427:431 arg1 age 433:435 mixed age 427:435 mixed age 427:435 METHODS Thirty-two mid-lactation grazing dairy cows of mixed age and breed were randomly allocated to one of four treatment groups in a 2 × 2 factorial arrangement: two prepartum BCS categories [4.0 (thin, BCS4) and 5.0 (optimal, BCS5); based on a 10-point scale], and two levels of energy intake during the 3 weeks preceding calving (75 and 125 % of estimated requirements). 27806685 7 128 theme prolonged 1555:1563 arg1 balance 1581:1587 a greater and more prolonged negative energy balance 1536:1587 a greater and more prolonged negative energy balance postpartum in BCS5 cows overfed prepartum 1536:1629 Altered carbohydrate and amino acid metabolism suggest a greater and more prolonged negative energy balance postpartum in BCS5 cows overfed prepartum. 27806685 0 129 theme nutrition 44:52 arg1 plane 35:39 plane 35:39 plane of nutrition 35:52 Prepartum body condition score and plane of nutrition affect the hepatic transcriptome during the transition period in grazing dairy cows. 27806685 0 129 theme nutrition 44:52 arg1 score 25:29 Prepartum body condition score 0:29 Prepartum body condition score 0:29 Prepartum body condition score and plane of nutrition affect the hepatic transcriptome during the transition period in grazing dairy cows. 27806685 2 130 dep calving 698:704 arg1 % 718:718 75 and 125 % 707:718 75 and 125 % of estimated requirements 707:744 METHODS Thirty-two mid-lactation grazing dairy cows of mixed age and breed were randomly allocated to one of four treatment groups in a 2 × 2 factorial arrangement: two prepartum BCS categories [4.0 (thin, BCS4) and 5.0 (optimal, BCS5); based on a 10-point scale], and two levels of energy intake during the 3 weeks preceding calving (75 and 125 % of estimated requirements). 27806685 2 130 dep calving 698:704 arg1 requirements 733:744 estimated requirements 723:744 estimated requirements 723:744 METHODS Thirty-two mid-lactation grazing dairy cows of mixed age and breed were randomly allocated to one of four treatment groups in a 2 × 2 factorial arrangement: two prepartum BCS categories [4.0 (thin, BCS4) and 5.0 (optimal, BCS5); based on a 10-point scale], and two levels of energy intake during the 3 weeks preceding calving (75 and 125 % of estimated requirements). 27806685 8 131 theme co-factor 1773:1781 arg1 metabolism 1783:1792 amino acid, vitamin, and co-factor metabolism 1748:1792 metabolism 1783:1792 This is supported by opposite effects of prepartum feeding in BCS4 compared with BCS5 cows in pathways encompassing amino acid, vitamin, and co-factor metabolism. 27806685 12 132 theme optimal 2414:2420 arg1 degree 2422:2427 optimal degree 2414:2427 optimal degree of body condition 2414:2445 CONCLUSION Overall, the data support the hypothesis that overfeeding in late-pregnancy should be limited to underconditioned cows, while cows with optimal degree of body condition should be maintained on an energy-restricted diet. 27806685 10 133 from Alterations 1985:1995 arg1 pathway 2033:2039 the glycosaminoglycans synthesis pathway 2000:2039 the glycosaminoglycans synthesis pathway 2000:2039 Alterations in the glycosaminoglycans synthesis pathway support this idea, indicating better hepatic health status in feed-restricted BCS5 and overfed BCS4 cows. 27806685 1 134 theme body 238:241 arg1 BCS 260:262 BCS 260:262 BCS 260:262 BACKGROUND A transcriptomic approach was used to evaluate potential interactions between prepartum body condition score (BCS) and feeding management in the weeks before calving on hepatic metabolism during the periparturient period. 27806685 1 134 theme body 238:241 arg1 score 253:257 prepartum body condition score 228:257 prepartum body condition score (BCS) 228:263 BACKGROUND A transcriptomic approach was used to evaluate potential interactions between prepartum body condition score (BCS) and feeding management in the weeks before calving on hepatic metabolism during the periparturient period. 27806685 2 135 dep [4.0 566:569 arg1 BCS4 578:581 BCS4 578:581 BCS4 578:581 METHODS Thirty-two mid-lactation grazing dairy cows of mixed age and breed were randomly allocated to one of four treatment groups in a 2 × 2 factorial arrangement: two prepartum BCS categories [4.0 (thin, BCS4) and 5.0 (optimal, BCS5); based on a 10-point scale], and two levels of energy intake during the 3 weeks preceding calving (75 and 125 % of estimated requirements). 27806685 2 135 dep [4.0 566:569 arg1 thin 572:575 thin 572:575 thin 572:575 METHODS Thirty-two mid-lactation grazing dairy cows of mixed age and breed were randomly allocated to one of four treatment groups in a 2 × 2 factorial arrangement: two prepartum BCS categories [4.0 (thin, BCS4) and 5.0 (optimal, BCS5); based on a 10-point scale], and two levels of energy intake during the 3 weeks preceding calving (75 and 125 % of estimated requirements). 27806685 3 136 theme Bovine 873:878 arg1 chip 896:899 the Agilent 44 K Bovine (V2) Microarray chip 856:899 the Agilent 44 K Bovine (V2) Microarray chip 856:899 Liver samples were obtained at -7, 7, and 28 d relative to parturition and subsequent RNA was hybridized to the Agilent 44 K Bovine (V2) Microarray chip. 27806685 11 137 theme liver 2190:2194 arg1 damage 2196:2201 liver damage 2190:2201 liver damage in feed-restricted thin cows 2190:2230 Furthermore, IPA network analysis suggests liver damage in feed-restricted thin cows, likely due to metabolic overload. 27806685 6 138 theme BCS 1342:1344 arg1 independent 1317:1327 independent 1317:1327 independent 1317:1327 However, independent of prepartum BCS, pathway analysis revealed that prepartal feeding level had a marked effect on carbohydrate, amino acid, lipid, and glycan metabolism. 27006333 4 0 theme vascular 474:481 arg1 receptor 509:516 vascular endothelial growth factor receptor 2 474:518 vascular endothelial growth factor receptor 2 (VEGFR2) 474:527 In CHO cells glycan-deficient PrP also interacts with glycosaminoglycan (GAG) and vascular endothelial growth factor receptor 2 (VEGFR2), resulting in VEGFR2 activation and enhanced Akt phosphorylation. 27006333 4 0 theme vascular 474:481 arg1 VEGFR2 521:526 VEGFR2 521:526 VEGFR2 521:526 In CHO cells glycan-deficient PrP also interacts with glycosaminoglycan (GAG) and vascular endothelial growth factor receptor 2 (VEGFR2), resulting in VEGFR2 activation and enhanced Akt phosphorylation. 27006333 5 1 theme glycan-deficient 629:644 arg1 PrP 646:648 glycan-deficient PrP 629:648 glycan-deficient PrP lacking the GAG binding motif 629:678 Accordingly, CHO cells expressing glycan-deficient PrP lacking the GAG binding motif or cells treated with heparinase to remove GAG show diminished Akt signaling. 27006333 2 2 from expression 257:266 arg1 glycans 203:209 the two glycans 195:209 the two glycans 195:209 In Chinese hamster ovary (CHO) cells, the two glycans are clearly not important in the cell surface expression of transfected human PrP. 27006333 2 2 from expression 257:266 arg1 important 227:235 important 227:235 important 227:235 In Chinese hamster ovary (CHO) cells, the two glycans are clearly not important in the cell surface expression of transfected human PrP. 27006333 8 3 from changes 1159:1165 arg1 behavior 1179:1186 cellular behavior 1170:1186 cellular behavior 1170:1186 Based on these findings, we propose a model in which glycan-deficient PrP, GAG, and VEGFR2 interact, activating VEGFR2 and resulting in changes in cellular behavior. 27006333 4 4 theme factor 502:507 arg1 receptor 509:516 vascular endothelial growth factor receptor 2 474:518 vascular endothelial growth factor receptor 2 (VEGFR2) 474:527 In CHO cells glycan-deficient PrP also interacts with glycosaminoglycan (GAG) and vascular endothelial growth factor receptor 2 (VEGFR2), resulting in VEGFR2 activation and enhanced Akt phosphorylation. 27006333 4 4 theme factor 502:507 arg1 VEGFR2 521:526 VEGFR2 521:526 VEGFR2 521:526 In CHO cells glycan-deficient PrP also interacts with glycosaminoglycan (GAG) and vascular endothelial growth factor receptor 2 (VEGFR2), resulting in VEGFR2 activation and enhanced Akt phosphorylation. 27006333 6 5 theme chimeric 791:798 arg1 PrP 817:819 chimeric glycan-deficient PrP 791:819 chimeric glycan-deficient PrP with CD4 transmembrane and cytoplasmic domains 791:866 Being in lipid raft is critical, chimeric glycan-deficient PrP with CD4 transmembrane and cytoplasmic domains is absent in lipid raft and does not activate Akt signaling. 27006333 4 6 theme VEGFR2 543:548 arg1 activation 550:559 VEGFR2 activation 543:559 VEGFR2 activation 543:559 In CHO cells glycan-deficient PrP also interacts with glycosaminoglycan (GAG) and vascular endothelial growth factor receptor 2 (VEGFR2), resulting in VEGFR2 activation and enhanced Akt phosphorylation. 27006333 6 7 from absent 871:876 arg1 raft 887:890 lipid raft 881:890 lipid raft 881:890 Being in lipid raft is critical, chimeric glycan-deficient PrP with CD4 transmembrane and cytoplasmic domains is absent in lipid raft and does not activate Akt signaling. 27006333 4 8 theme growth 495:500 arg1 receptor 509:516 vascular endothelial growth factor receptor 2 474:518 vascular endothelial growth factor receptor 2 (VEGFR2) 474:527 In CHO cells glycan-deficient PrP also interacts with glycosaminoglycan (GAG) and vascular endothelial growth factor receptor 2 (VEGFR2), resulting in VEGFR2 activation and enhanced Akt phosphorylation. 27006333 4 8 theme growth 495:500 arg1 VEGFR2 521:526 VEGFR2 521:526 VEGFR2 521:526 In CHO cells glycan-deficient PrP also interacts with glycosaminoglycan (GAG) and vascular endothelial growth factor receptor 2 (VEGFR2), resulting in VEGFR2 activation and enhanced Akt phosphorylation. 27006333 7 9 theme glycan-deficient 947:962 arg1 PrP 964:966 glycan-deficient PrP 947:966 glycan-deficient PrP 947:966 CHO cells bearing glycan-deficient PrP also exhibit enhanced cellular adhesion and migration. 27006333 2 10 theme surface 249:255 arg1 expression 257:266 the cell surface expression 240:266 the cell surface expression of transfected human PrP 240:291 In Chinese hamster ovary (CHO) cells, the two glycans are clearly not important in the cell surface expression of transfected human PrP. 27006333 4 11 theme enhanced 565:572 arg1 phosphorylation 578:592 enhanced Akt phosphorylation 565:592 enhanced Akt phosphorylation 565:592 In CHO cells glycan-deficient PrP also interacts with glycosaminoglycan (GAG) and vascular endothelial growth factor receptor 2 (VEGFR2), resulting in VEGFR2 activation and enhanced Akt phosphorylation. 27006333 3 12 theme glycan-deficient 330:345 arg1 PrP 347:349 glycan-deficient PrP 330:349 glycan-deficient PrP 330:349 Compared to fully-glycosylated PrP, glycan-deficient PrP preferentially partitions to lipid raft. 27006333 6 13 theme lipid 881:885 arg1 raft 887:890 lipid raft 881:890 lipid raft 881:890 Being in lipid raft is critical, chimeric glycan-deficient PrP with CD4 transmembrane and cytoplasmic domains is absent in lipid raft and does not activate Akt signaling. 27006333 7 14 theme CHO 929:931 arg1 cells 933:937 CHO cells 929:937 CHO cells bearing glycan-deficient PrP 929:966 CHO cells bearing glycan-deficient PrP also exhibit enhanced cellular adhesion and migration. 27006333 2 15 theme cell 244:247 arg1 expression 257:266 the cell surface expression 240:266 the cell surface expression of transfected human PrP 240:291 In Chinese hamster ovary (CHO) cells, the two glycans are clearly not important in the cell surface expression of transfected human PrP. 27006333 3 16 theme fully-glycosylated 306:323 arg1 PrP 325:327 fully-glycosylated PrP 306:327 fully-glycosylated PrP 306:327 Compared to fully-glycosylated PrP, glycan-deficient PrP preferentially partitions to lipid raft. 27006333 5 17 theme CHO 608:610 arg1 cells 612:616 CHO cells 608:616 CHO cells expressing glycan-deficient PrP lacking the GAG binding motif or cells treated with heparinase to remove GAG 608:725 Accordingly, CHO cells expressing glycan-deficient PrP lacking the GAG binding motif or cells treated with heparinase to remove GAG show diminished Akt signaling. 27006333 1 18 theme N-linked 88:95 arg1 important 109:117 important 109:117 important 109:117 Whether the two N-linked glycans are important in prion, PrP, biology is unresolved. 27006333 1 18 theme N-linked 88:95 arg1 glycans 97:103 the two N-linked glycans 80:103 the two N-linked glycans 80:103 Whether the two N-linked glycans are important in prion, PrP, biology is unresolved. 27006333 2 19 from cells 188:192 arg1 glycans 203:209 the two glycans 195:209 the two glycans 195:209 In Chinese hamster ovary (CHO) cells, the two glycans are clearly not important in the cell surface expression of transfected human PrP. 27006333 2 19 from cells 188:192 arg1 important 227:235 important 227:235 important 227:235 In Chinese hamster ovary (CHO) cells, the two glycans are clearly not important in the cell surface expression of transfected human PrP. 27006333 6 20 theme lipid 767:771 arg1 raft 773:776 lipid raft 767:776 lipid raft 767:776 Being in lipid raft is critical, chimeric glycan-deficient PrP with CD4 transmembrane and cytoplasmic domains is absent in lipid raft and does not activate Akt signaling. 27006333 2 21 theme human 283:287 arg1 PrP 289:291 transfected human PrP 271:291 transfected human PrP 271:291 In Chinese hamster ovary (CHO) cells, the two glycans are clearly not important in the cell surface expression of transfected human PrP. 27006333 8 22 theme glycan-deficient 1076:1091 arg1 PrP 1093:1095 glycan-deficient PrP 1076:1095 glycan-deficient PrP 1076:1095 Based on these findings, we propose a model in which glycan-deficient PrP, GAG, and VEGFR2 interact, activating VEGFR2 and resulting in changes in cellular behavior. 27006333 0 23 theme Glycan-deficient 0:15 arg1 PrP 17:19 Glycan-deficient PrP 0:19 Glycan-deficient PrP 0:19 Glycan-deficient PrP stimulates VEGFR2 signaling via glycosaminoglycan. 27006333 6 24 theme glycan-deficient 800:815 arg1 PrP 817:819 chimeric glycan-deficient PrP 791:819 chimeric glycan-deficient PrP with CD4 transmembrane and cytoplasmic domains 791:866 Being in lipid raft is critical, chimeric glycan-deficient PrP with CD4 transmembrane and cytoplasmic domains is absent in lipid raft and does not activate Akt signaling. 27006333 1 25 from prion 122:126 arg1 important 109:117 important 109:117 important 109:117 Whether the two N-linked glycans are important in prion, PrP, biology is unresolved. 27006333 1 25 from prion 122:126 arg1 glycans 97:103 the two N-linked glycans 80:103 the two N-linked glycans 80:103 Whether the two N-linked glycans are important in prion, PrP, biology is unresolved. 27006333 2 26 theme transfected 271:281 arg1 PrP 289:291 transfected human PrP 271:291 transfected human PrP 271:291 In Chinese hamster ovary (CHO) cells, the two glycans are clearly not important in the cell surface expression of transfected human PrP. 27006333 6 27 theme cytoplasmic 848:858 arg1 domains 860:866 CD4 transmembrane and cytoplasmic domains 826:866 CD4 transmembrane and cytoplasmic domains 826:866 Being in lipid raft is critical, chimeric glycan-deficient PrP with CD4 transmembrane and cytoplasmic domains is absent in lipid raft and does not activate Akt signaling. 27006333 0 28 theme VEGFR2 32:37 arg1 signaling 39:47 VEGFR2 signaling 32:47 VEGFR2 signaling 32:47 Glycan-deficient PrP stimulates VEGFR2 signaling via glycosaminoglycan. 27006333 6 29 with PrP 817:819 arg1 domains 860:866 CD4 transmembrane and cytoplasmic domains 826:866 CD4 transmembrane and cytoplasmic domains 826:866 Being in lipid raft is critical, chimeric glycan-deficient PrP with CD4 transmembrane and cytoplasmic domains is absent in lipid raft and does not activate Akt signaling. 27006333 2 30 theme ovary 176:180 arg1 cells 188:192 Chinese hamster ovary (CHO) cells 160:192 Chinese hamster ovary (CHO) cells 160:192 In Chinese hamster ovary (CHO) cells, the two glycans are clearly not important in the cell surface expression of transfected human PrP. 27006333 2 31 from important 227:235 arg1 expression 257:266 the cell surface expression 240:266 the cell surface expression of transfected human PrP 240:291 In Chinese hamster ovary (CHO) cells, the two glycans are clearly not important in the cell surface expression of transfected human PrP. 27006333 2 31 from important 227:235 arg1 cells 188:192 Chinese hamster ovary (CHO) cells 160:192 Chinese hamster ovary (CHO) cells 160:192 In Chinese hamster ovary (CHO) cells, the two glycans are clearly not important in the cell surface expression of transfected human PrP. 27006333 2 32 theme hamster 168:174 arg1 cells 188:192 Chinese hamster ovary (CHO) cells 160:192 Chinese hamster ovary (CHO) cells 160:192 In Chinese hamster ovary (CHO) cells, the two glycans are clearly not important in the cell surface expression of transfected human PrP. 27006333 8 33 theme cellular 1170:1177 arg1 behavior 1179:1186 cellular behavior 1170:1186 cellular behavior 1170:1186 Based on these findings, we propose a model in which glycan-deficient PrP, GAG, and VEGFR2 interact, activating VEGFR2 and resulting in changes in cellular behavior. 27006333 3 34 gly fully-glycosylated 306:323 arg1 PrP 325:327 fully-glycosylated PrP 306:327 fully-glycosylated PrP 306:327 Compared to fully-glycosylated PrP, glycan-deficient PrP preferentially partitions to lipid raft. 27006333 2 35 theme Chinese 160:166 arg1 cells 188:192 Chinese hamster ovary (CHO) cells 160:192 Chinese hamster ovary (CHO) cells 160:192 In Chinese hamster ovary (CHO) cells, the two glycans are clearly not important in the cell surface expression of transfected human PrP. 27006333 3 36 theme lipid 380:384 arg1 raft 386:389 lipid raft 380:389 lipid raft 380:389 Compared to fully-glycosylated PrP, glycan-deficient PrP preferentially partitions to lipid raft. 27006333 5 37 theme GAG 662:664 arg1 motif 674:678 the GAG binding motif 658:678 the GAG binding motif 658:678 Accordingly, CHO cells expressing glycan-deficient PrP lacking the GAG binding motif or cells treated with heparinase to remove GAG show diminished Akt signaling. 27006333 6 38 theme transmembrane 830:842 arg1 domains 860:866 CD4 transmembrane and cytoplasmic domains 826:866 CD4 transmembrane and cytoplasmic domains 826:866 Being in lipid raft is critical, chimeric glycan-deficient PrP with CD4 transmembrane and cytoplasmic domains is absent in lipid raft and does not activate Akt signaling. 27006333 6 39 theme Akt 914:916 arg1 signaling 918:926 Akt signaling 914:926 Akt signaling 914:926 Being in lipid raft is critical, chimeric glycan-deficient PrP with CD4 transmembrane and cytoplasmic domains is absent in lipid raft and does not activate Akt signaling. 27006333 5 40 theme binding 666:672 arg1 motif 674:678 the GAG binding motif 658:678 the GAG binding motif 658:678 Accordingly, CHO cells expressing glycan-deficient PrP lacking the GAG binding motif or cells treated with heparinase to remove GAG show diminished Akt signaling. 27006333 6 41 theme CD4 826:828 arg1 domains 860:866 CD4 transmembrane and cytoplasmic domains 826:866 CD4 transmembrane and cytoplasmic domains 826:866 Being in lipid raft is critical, chimeric glycan-deficient PrP with CD4 transmembrane and cytoplasmic domains is absent in lipid raft and does not activate Akt signaling. 27006333 7 42 theme cellular 990:997 arg1 adhesion 999:1006 enhanced cellular adhesion 981:1006 enhanced cellular adhesion 981:1006 CHO cells bearing glycan-deficient PrP also exhibit enhanced cellular adhesion and migration. 27006333 1 43 from important 109:117 arg1 PrP 129:131 PrP 129:131 PrP 129:131 Whether the two N-linked glycans are important in prion, PrP, biology is unresolved. 27006333 1 43 from important 109:117 arg1 prion 122:126 prion 122:126 prion 122:126 Whether the two N-linked glycans are important in prion, PrP, biology is unresolved. 27006333 6 44 from raft 887:890 arg1 absent 871:876 absent 871:876 absent 871:876 Being in lipid raft is critical, chimeric glycan-deficient PrP with CD4 transmembrane and cytoplasmic domains is absent in lipid raft and does not activate Akt signaling. 27006333 4 45 theme CHO 395:397 arg1 cells 399:403 CHO cells 395:403 CHO cells 395:403 In CHO cells glycan-deficient PrP also interacts with glycosaminoglycan (GAG) and vascular endothelial growth factor receptor 2 (VEGFR2), resulting in VEGFR2 activation and enhanced Akt phosphorylation. 27006333 2 46 theme CHO 183:185 arg1 cells 188:192 Chinese hamster ovary (CHO) cells 160:192 Chinese hamster ovary (CHO) cells 160:192 In Chinese hamster ovary (CHO) cells, the two glycans are clearly not important in the cell surface expression of transfected human PrP. 27006333 2 47 theme PrP 289:291 arg1 expression 257:266 the cell surface expression 240:266 the cell surface expression of transfected human PrP 240:291 In Chinese hamster ovary (CHO) cells, the two glycans are clearly not important in the cell surface expression of transfected human PrP. 27006333 4 48 theme Akt 574:576 arg1 phosphorylation 578:592 enhanced Akt phosphorylation 565:592 enhanced Akt phosphorylation 565:592 In CHO cells glycan-deficient PrP also interacts with glycosaminoglycan (GAG) and vascular endothelial growth factor receptor 2 (VEGFR2), resulting in VEGFR2 activation and enhanced Akt phosphorylation. 27006333 5 49 theme diminished 732:741 arg1 signaling 747:755 diminished Akt signaling 732:755 diminished Akt signaling 732:755 Accordingly, CHO cells expressing glycan-deficient PrP lacking the GAG binding motif or cells treated with heparinase to remove GAG show diminished Akt signaling. 27006333 4 50 theme glycan-deficient 405:420 arg1 PrP 422:424 glycan-deficient PrP 405:424 glycan-deficient PrP 405:424 In CHO cells glycan-deficient PrP also interacts with glycosaminoglycan (GAG) and vascular endothelial growth factor receptor 2 (VEGFR2), resulting in VEGFR2 activation and enhanced Akt phosphorylation. 27006333 7 51 theme enhanced 981:988 arg1 adhesion 999:1006 enhanced cellular adhesion 981:1006 enhanced cellular adhesion 981:1006 CHO cells bearing glycan-deficient PrP also exhibit enhanced cellular adhesion and migration. 27006333 5 52 theme Akt 743:745 arg1 signaling 747:755 diminished Akt signaling 732:755 diminished Akt signaling 732:755 Accordingly, CHO cells expressing glycan-deficient PrP lacking the GAG binding motif or cells treated with heparinase to remove GAG show diminished Akt signaling. 27006333 4 53 theme endothelial 483:493 arg1 receptor 509:516 vascular endothelial growth factor receptor 2 474:518 vascular endothelial growth factor receptor 2 (VEGFR2) 474:527 In CHO cells glycan-deficient PrP also interacts with glycosaminoglycan (GAG) and vascular endothelial growth factor receptor 2 (VEGFR2), resulting in VEGFR2 activation and enhanced Akt phosphorylation. 27006333 4 53 theme endothelial 483:493 arg1 VEGFR2 521:526 VEGFR2 521:526 VEGFR2 521:526 In CHO cells glycan-deficient PrP also interacts with glycosaminoglycan (GAG) and vascular endothelial growth factor receptor 2 (VEGFR2), resulting in VEGFR2 activation and enhanced Akt phosphorylation. 27006333 1 54 link N-linked 88:95 arg1 important 109:117 important 109:117 important 109:117 Whether the two N-linked glycans are important in prion, PrP, biology is unresolved. 27006333 1 54 link N-linked 88:95 arg1 glycans 97:103 the two N-linked glycans 80:103 the two N-linked glycans 80:103 Whether the two N-linked glycans are important in prion, PrP, biology is unresolved. 25253073 13 0 theme strain 1362:1367 arg1 T 1377:1377 T 1377:1377 T 1377:1377 Based on its phenotypic and genotypic properties, strain LAM0410(T) represents a novel species of the genus Microbacterium, for which the name Microbacterium petrolearium sp. 25253073 13 0 theme strain 1362:1367 arg1 LAM0410 1369:1375 strain LAM0410 1362:1375 strain LAM0410(T) 1362:1378 Based on its phenotypic and genotypic properties, strain LAM0410(T) represents a novel species of the genus Microbacterium, for which the name Microbacterium petrolearium sp. 25253073 4 1 dep 12  442:444 arg1 to 439:440 to 439:440 to 439:440 The strain did not need NaCl for growth, but could tolerate a concentration of up to 12 % (w/v). 25253073 11 2 theme % 1121:1121 arg1 similarities 1132:1143 97.4 % sequence similarities 1116:1143 97.4 % sequence similarities 1116:1143 16S rRNA gene sequence analysis indicated that the isolate belonged to the genus Microbacterium and was closely related to Microbacterium sediminis MCCC 1A06153(T) and Microbacterium murale DSM 22178(T) with 97.5 % and 97.4 % sequence similarities, respectively; while the DNA-DNA hybridization values were 33.1±3.4 % and 21.8±1.6 %, respectively. 25253073 9 3 theme unknown 799:805 arg1 glycolipids 807:817 nine unknown glycolipids 794:817 nine unknown glycolipids 794:817 The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol and nine unknown glycolipids. 25253073 11 4 theme rRNA 901:904 arg1 analysis 920:927 16S rRNA gene sequence analysis 897:927 16S rRNA gene sequence analysis 897:927 16S rRNA gene sequence analysis indicated that the isolate belonged to the genus Microbacterium and was closely related to Microbacterium sediminis MCCC 1A06153(T) and Microbacterium murale DSM 22178(T) with 97.5 % and 97.4 % sequence similarities, respectively; while the DNA-DNA hybridization values were 33.1±3.4 % and 21.8±1.6 %, respectively. 25253073 12 5 theme mol 1274:1276 arg1 % 1277:1277 67.4 mol% 1269:1277 67.4 mol% 1269:1277 The DNA G+C content was 67.4 mol%, as determined by the Tm method. 25253073 12 5 theme mol 1274:1276 arg1 content 1257:1263 The DNA G+C content 1245:1263 The DNA G+C content 1245:1263 The DNA G+C content was 67.4 mol%, as determined by the Tm method. 25253073 14 6 dep LAM0410 1524:1530 arg1 T 1565:1565 T 1565:1565 T 1565:1565 nov. is proposed; the type strain is LAM0410(T) ( = ACCC 00719(T) = JCM 19612(T)). 25253073 14 6 dep LAM0410 1524:1530 arg1 19612 1559:1563  = ACCC 00719(T) = JCM 19612 1536:1563  = ACCC 00719(T) = JCM 19612(T) 1536:1566 nov. is proposed; the type strain is LAM0410(T) ( = ACCC 00719(T) = JCM 19612(T)). 25253073 9 7 theme major 721:725 arg1 diphosphatidylglycerol 745:766 diphosphatidylglycerol 745:766 diphosphatidylglycerol 745:766 The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol and nine unknown glycolipids. 25253073 9 7 theme major 721:725 arg1 lipids 733:738 The major polar lipids 717:738 The major polar lipids 717:738 The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol and nine unknown glycolipids. 25253073 5 8 from isolate 486:492 arg1 hydrolysates 464:475 Cell wall hydrolysates 454:475 Cell wall hydrolysates from the isolate 454:492 Cell wall hydrolysates from the isolate showed that the diamino acid was ornithine. 25253073 8 9 theme respiratory 667:677 arg1 quinones 679:686 The major respiratory quinones 657:686 The major respiratory quinones 657:686 The major respiratory quinones were MK-10, MK-11 and MK-12. 25253073 8 9 theme respiratory 667:677 arg1 MK-10 693:697 MK-10 693:697 MK-10 693:697 The major respiratory quinones were MK-10, MK-11 and MK-12. 25253073 2 10 dep Gram-staining-positive 88:109 arg1 aerobic 124:130 aerobic 124:130 aerobic 124:130 A Gram-staining-positive, rod-shaped, aerobic bacterium, designated strain LAM0410(T), was isolated from an oil-contaminated water sample from the Dagang Oilfield, PR China. 25253073 2 10 dep Gram-staining-positive 88:109 arg1 rod-shaped 112:121 rod-shaped 112:121 rod-shaped 112:121 A Gram-staining-positive, rod-shaped, aerobic bacterium, designated strain LAM0410(T), was isolated from an oil-contaminated water sample from the Dagang Oilfield, PR China. 25253073 11 11 theme sequence 1123:1130 arg1 similarities 1132:1143 97.4 % sequence similarities 1116:1143 97.4 % sequence similarities 1116:1143 16S rRNA gene sequence analysis indicated that the isolate belonged to the genus Microbacterium and was closely related to Microbacterium sediminis MCCC 1A06153(T) and Microbacterium murale DSM 22178(T) with 97.5 % and 97.4 % sequence similarities, respectively; while the DNA-DNA hybridization values were 33.1±3.4 % and 21.8±1.6 %, respectively. 25253073 11 12 theme sediminis 1035:1043 arg1 MCCC 1045:1048 Microbacterium sediminis MCCC 1A06153 1020:1056 Microbacterium sediminis MCCC 1A06153(T) 1020:1059 16S rRNA gene sequence analysis indicated that the isolate belonged to the genus Microbacterium and was closely related to Microbacterium sediminis MCCC 1A06153(T) and Microbacterium murale DSM 22178(T) with 97.5 % and 97.4 % sequence similarities, respectively; while the DNA-DNA hybridization values were 33.1±3.4 % and 21.8±1.6 %, respectively. 25253073 11 12 theme sediminis 1035:1043 arg1 T 1058:1058 T 1058:1058 T 1058:1058 16S rRNA gene sequence analysis indicated that the isolate belonged to the genus Microbacterium and was closely related to Microbacterium sediminis MCCC 1A06153(T) and Microbacterium murale DSM 22178(T) with 97.5 % and 97.4 % sequence similarities, respectively; while the DNA-DNA hybridization values were 33.1±3.4 % and 21.8±1.6 %, respectively. 25253073 10 13 theme major 824:828 arg1 acids 836:840 The major fatty acids 820:840 The major fatty acids 820:840 The major fatty acids were anteiso-C15 : 0, anteiso-C17 : 0 and iso-C16 : 0. 25253073 10 13 theme major 824:828 arg1 anteiso-C15  847:858 anteiso-C15  847:858 anteiso-C15  847:858 The major fatty acids were anteiso-C15 : 0, anteiso-C17 : 0 and iso-C16 : 0. 25253073 7 14 theme glycan 595:600 arg1 moiety 602:607 The glycan moiety 591:607 The glycan moiety of the cell wall 591:624 The glycan moiety of the cell wall contained N-glycolyl residues. 25253073 11 15 theme 97.4  1116:1120 arg1 % 1121:1121 % 1121:1121 % 1121:1121 16S rRNA gene sequence analysis indicated that the isolate belonged to the genus Microbacterium and was closely related to Microbacterium sediminis MCCC 1A06153(T) and Microbacterium murale DSM 22178(T) with 97.5 % and 97.4 % sequence similarities, respectively; while the DNA-DNA hybridization values were 33.1±3.4 % and 21.8±1.6 %, respectively. 25253073 1 16 theme oil-contaminated 55:70 arg1 sample 78:83 an oil-contaminated water sample 52:83 an oil-contaminated water sample 52:83 nov., isolated from an oil-contaminated water sample. 25253073 3 17 theme °C 308:309 arg1 ranges 283:288 The temperature and pH ranges 260:288 ranges 283:288 The temperature and pH ranges for growth were 4 °C to 50 °C and pH 4.4 to pH 12.0, respectively. 25253073 3 17 theme °C 308:309 arg1 °C 317:318 4 °C to 50 °C 306:318 4 °C to 50 °C 306:318 The temperature and pH ranges for growth were 4 °C to 50 °C and pH 4.4 to pH 12.0, respectively. 25253073 2 18 theme strain 154:159 arg1 T 169:169 T 169:169 T 169:169 A Gram-staining-positive, rod-shaped, aerobic bacterium, designated strain LAM0410(T), was isolated from an oil-contaminated water sample from the Dagang Oilfield, PR China. 25253073 2 18 theme strain 154:159 arg1 LAM0410 161:167 strain LAM0410 154:167 strain LAM0410(T) 154:170 A Gram-staining-positive, rod-shaped, aerobic bacterium, designated strain LAM0410(T), was isolated from an oil-contaminated water sample from the Dagang Oilfield, PR China. 25253073 13 19 theme Microbacterium 1455:1468 arg1 sp 1483:1484 the name Microbacterium petrolearium sp 1446:1484 the name Microbacterium petrolearium sp 1446:1484 Based on its phenotypic and genotypic properties, strain LAM0410(T) represents a novel species of the genus Microbacterium, for which the name Microbacterium petrolearium sp. 25253073 11 20 theme genus 972:976 arg1 Microbacterium 978:991 the genus Microbacterium 968:991 the genus Microbacterium 968:991 16S rRNA gene sequence analysis indicated that the isolate belonged to the genus Microbacterium and was closely related to Microbacterium sediminis MCCC 1A06153(T) and Microbacterium murale DSM 22178(T) with 97.5 % and 97.4 % sequence similarities, respectively; while the DNA-DNA hybridization values were 33.1±3.4 % and 21.8±1.6 %, respectively. 25253073 1 21 theme water 72:76 arg1 sample 78:83 an oil-contaminated water sample 52:83 an oil-contaminated water sample 52:83 nov., isolated from an oil-contaminated water sample. 25253073 5 22 theme diamino 510:516 arg1 acid 518:521 the diamino acid 506:521 the diamino acid 506:521 Cell wall hydrolysates from the isolate showed that the diamino acid was ornithine. 25253073 5 22 theme diamino 510:516 arg1 ornithine 527:535 ornithine 527:535 ornithine 527:535 Cell wall hydrolysates from the isolate showed that the diamino acid was ornithine. 25253073 5 23 theme Cell 454:457 arg1 hydrolysates 464:475 Cell wall hydrolysates 454:475 Cell wall hydrolysates from the isolate 454:492 Cell wall hydrolysates from the isolate showed that the diamino acid was ornithine. 25253073 11 24 theme hybridization 1178:1190 arg1 values 1192:1197 the DNA-DNA hybridization values 1166:1197 the DNA-DNA hybridization values 1166:1197 16S rRNA gene sequence analysis indicated that the isolate belonged to the genus Microbacterium and was closely related to Microbacterium sediminis MCCC 1A06153(T) and Microbacterium murale DSM 22178(T) with 97.5 % and 97.4 % sequence similarities, respectively; while the DNA-DNA hybridization values were 33.1±3.4 % and 21.8±1.6 %, respectively. 25253073 11 24 theme hybridization 1178:1190 arg1 % 1213:1213 33.1±3.4 % 1204:1213 33.1±3.4 % 1204:1213 16S rRNA gene sequence analysis indicated that the isolate belonged to the genus Microbacterium and was closely related to Microbacterium sediminis MCCC 1A06153(T) and Microbacterium murale DSM 22178(T) with 97.5 % and 97.4 % sequence similarities, respectively; while the DNA-DNA hybridization values were 33.1±3.4 % and 21.8±1.6 %, respectively. 25253073 14 25 theme  = ACCC 1536:1542 arg1 T 1565:1565 T 1565:1565 T 1565:1565 nov. is proposed; the type strain is LAM0410(T) ( = ACCC 00719(T) = JCM 19612(T)). 25253073 14 25 theme  = ACCC 1536:1542 arg1 19612 1559:1563  = ACCC 00719(T) = JCM 19612 1536:1563  = ACCC 00719(T) = JCM 19612(T) 1536:1566 nov. is proposed; the type strain is LAM0410(T) ( = ACCC 00719(T) = JCM 19612(T)). 25253073 0 26 theme petrolearium 15:26 arg1 sp 28:29 Microbacterium petrolearium sp 0:29 Microbacterium petrolearium sp. 0:30 Microbacterium petrolearium sp. 25253073 6 27 contain contained 559:567 arg2 galactose 580:588 galactose 580:588 galactose 580:588 The cell wall sugars contained ribose and galactose. 25253073 6 27 contain contained 559:567 arg2 ribose 569:574 ribose 569:574 ribose 569:574 The cell wall sugars contained ribose and galactose. 25253073 6 27 contain contained 559:567 arg1 sugars 552:557 The cell wall sugars 538:557 The cell wall sugars 538:557 The cell wall sugars contained ribose and galactose. 25253073 5 28 theme wall 459:462 arg1 hydrolysates 464:475 Cell wall hydrolysates 454:475 Cell wall hydrolysates from the isolate 454:492 Cell wall hydrolysates from the isolate showed that the diamino acid was ornithine. 25253073 11 29 theme Microbacterium 1065:1078 arg1 DSM 1087:1089 Microbacterium murale DSM 22178 1065:1095 Microbacterium murale DSM 22178(T) 1065:1098 16S rRNA gene sequence analysis indicated that the isolate belonged to the genus Microbacterium and was closely related to Microbacterium sediminis MCCC 1A06153(T) and Microbacterium murale DSM 22178(T) with 97.5 % and 97.4 % sequence similarities, respectively; while the DNA-DNA hybridization values were 33.1±3.4 % and 21.8±1.6 %, respectively. 25253073 11 29 theme Microbacterium 1065:1078 arg1 T 1097:1097 T 1097:1097 T 1097:1097 16S rRNA gene sequence analysis indicated that the isolate belonged to the genus Microbacterium and was closely related to Microbacterium sediminis MCCC 1A06153(T) and Microbacterium murale DSM 22178(T) with 97.5 % and 97.4 % sequence similarities, respectively; while the DNA-DNA hybridization values were 33.1±3.4 % and 21.8±1.6 %, respectively. 25253073 12 30 theme G+C 1253:1255 arg1 % 1277:1277 67.4 mol% 1269:1277 67.4 mol% 1269:1277 The DNA G+C content was 67.4 mol%, as determined by the Tm method. 25253073 12 30 theme G+C 1253:1255 arg1 content 1257:1263 The DNA G+C content 1245:1263 The DNA G+C content 1245:1263 The DNA G+C content was 67.4 mol%, as determined by the Tm method. 25253073 0 31 theme Microbacterium 0:13 arg1 sp 28:29 Microbacterium petrolearium sp 0:29 Microbacterium petrolearium sp. 0:30 Microbacterium petrolearium sp. 25253073 9 32 theme polar 727:731 arg1 diphosphatidylglycerol 745:766 diphosphatidylglycerol 745:766 diphosphatidylglycerol 745:766 The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol and nine unknown glycolipids. 25253073 9 32 theme polar 727:731 arg1 lipids 733:738 The major polar lipids 717:738 The major polar lipids 717:738 The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol and nine unknown glycolipids. 25253073 11 33 theme murale 1080:1085 arg1 DSM 1087:1089 Microbacterium murale DSM 22178 1065:1095 Microbacterium murale DSM 22178(T) 1065:1098 16S rRNA gene sequence analysis indicated that the isolate belonged to the genus Microbacterium and was closely related to Microbacterium sediminis MCCC 1A06153(T) and Microbacterium murale DSM 22178(T) with 97.5 % and 97.4 % sequence similarities, respectively; while the DNA-DNA hybridization values were 33.1±3.4 % and 21.8±1.6 %, respectively. 25253073 11 33 theme murale 1080:1085 arg1 T 1097:1097 T 1097:1097 T 1097:1097 16S rRNA gene sequence analysis indicated that the isolate belonged to the genus Microbacterium and was closely related to Microbacterium sediminis MCCC 1A06153(T) and Microbacterium murale DSM 22178(T) with 97.5 % and 97.4 % sequence similarities, respectively; while the DNA-DNA hybridization values were 33.1±3.4 % and 21.8±1.6 %, respectively. 25253073 13 34 theme phenotypic 1325:1334 arg1 properties 1350:1359 its phenotypic and genotypic properties 1321:1359 its phenotypic and genotypic properties 1321:1359 Based on its phenotypic and genotypic properties, strain LAM0410(T) represents a novel species of the genus Microbacterium, for which the name Microbacterium petrolearium sp. 25253073 2 35 attach isolated 177:184 arg1 sample 217:222 an oil-contaminated water sample 191:222 an oil-contaminated water sample from the Dagang Oilfield, PR China 191:257 A Gram-staining-positive, rod-shaped, aerobic bacterium, designated strain LAM0410(T), was isolated from an oil-contaminated water sample from the Dagang Oilfield, PR China. 25253073 2 35 attach isolated 177:184 arg2 bacterium 132:140 A Gram-staining-positive, rod-shaped, aerobic bacterium 86:140 A Gram-staining-positive, rod-shaped, aerobic bacterium 86:140 A Gram-staining-positive, rod-shaped, aerobic bacterium, designated strain LAM0410(T), was isolated from an oil-contaminated water sample from the Dagang Oilfield, PR China. 25253073 14 36 theme  = JCM 1552:1557 arg1 T 1565:1565 T 1565:1565 T 1565:1565 nov. is proposed; the type strain is LAM0410(T) ( = ACCC 00719(T) = JCM 19612(T)). 25253073 14 36 theme  = JCM 1552:1557 arg1 19612 1559:1563  = ACCC 00719(T) = JCM 19612 1536:1563  = ACCC 00719(T) = JCM 19612(T) 1536:1566 nov. is proposed; the type strain is LAM0410(T) ( = ACCC 00719(T) = JCM 19612(T)). 25253073 13 37 theme novel 1393:1397 arg1 species 1399:1405 a novel species 1391:1405 a novel species 1391:1405 Based on its phenotypic and genotypic properties, strain LAM0410(T) represents a novel species of the genus Microbacterium, for which the name Microbacterium petrolearium sp. 25253073 12 38 theme DNA 1249:1251 arg1 % 1277:1277 67.4 mol% 1269:1277 67.4 mol% 1269:1277 The DNA G+C content was 67.4 mol%, as determined by the Tm method. 25253073 12 38 theme DNA 1249:1251 arg1 content 1257:1263 The DNA G+C content 1245:1263 The DNA G+C content 1245:1263 The DNA G+C content was 67.4 mol%, as determined by the Tm method. 25253073 10 39 theme fatty 830:834 arg1 acids 836:840 The major fatty acids 820:840 The major fatty acids 820:840 The major fatty acids were anteiso-C15 : 0, anteiso-C17 : 0 and iso-C16 : 0. 25253073 10 39 theme fatty 830:834 arg1 anteiso-C15  847:858 anteiso-C15  847:858 anteiso-C15  847:858 The major fatty acids were anteiso-C15 : 0, anteiso-C17 : 0 and iso-C16 : 0. 25253073 11 40 theme sequence 911:918 arg1 analysis 920:927 16S rRNA gene sequence analysis 897:927 16S rRNA gene sequence analysis 897:927 16S rRNA gene sequence analysis indicated that the isolate belonged to the genus Microbacterium and was closely related to Microbacterium sediminis MCCC 1A06153(T) and Microbacterium murale DSM 22178(T) with 97.5 % and 97.4 % sequence similarities, respectively; while the DNA-DNA hybridization values were 33.1±3.4 % and 21.8±1.6 %, respectively. 25253073 14 41 theme T 1550:1550 arg1 T 1565:1565 T 1565:1565 T 1565:1565 nov. is proposed; the type strain is LAM0410(T) ( = ACCC 00719(T) = JCM 19612(T)). 25253073 14 41 theme T 1550:1550 arg1 19612 1559:1563  = ACCC 00719(T) = JCM 19612 1536:1563  = ACCC 00719(T) = JCM 19612(T) 1536:1566 nov. is proposed; the type strain is LAM0410(T) ( = ACCC 00719(T) = JCM 19612(T)). 25253073 14 42 theme 00719 1544:1548 arg1 T 1565:1565 T 1565:1565 T 1565:1565 nov. is proposed; the type strain is LAM0410(T) ( = ACCC 00719(T) = JCM 19612(T)). 25253073 14 42 theme 00719 1544:1548 arg1 19612 1559:1563  = ACCC 00719(T) = JCM 19612 1536:1563  = ACCC 00719(T) = JCM 19612(T) 1536:1566 nov. is proposed; the type strain is LAM0410(T) ( = ACCC 00719(T) = JCM 19612(T)). 25253073 6 43 theme wall 547:550 arg1 sugars 552:557 The cell wall sugars 538:557 The cell wall sugars 538:557 The cell wall sugars contained ribose and galactose. 25253073 6 44 theme cell 542:545 arg1 sugars 552:557 The cell wall sugars 538:557 The cell wall sugars 538:557 The cell wall sugars contained ribose and galactose. 25253073 13 45 theme name 1450:1453 arg1 sp 1483:1484 the name Microbacterium petrolearium sp 1446:1484 the name Microbacterium petrolearium sp 1446:1484 Based on its phenotypic and genotypic properties, strain LAM0410(T) represents a novel species of the genus Microbacterium, for which the name Microbacterium petrolearium sp. 25253073 8 46 theme major 661:665 arg1 quinones 679:686 The major respiratory quinones 657:686 The major respiratory quinones 657:686 The major respiratory quinones were MK-10, MK-11 and MK-12. 25253073 8 46 theme major 661:665 arg1 MK-10 693:697 MK-10 693:697 MK-10 693:697 The major respiratory quinones were MK-10, MK-11 and MK-12. 25253073 11 47 theme gene 906:909 arg1 analysis 920:927 16S rRNA gene sequence analysis 897:927 16S rRNA gene sequence analysis 897:927 16S rRNA gene sequence analysis indicated that the isolate belonged to the genus Microbacterium and was closely related to Microbacterium sediminis MCCC 1A06153(T) and Microbacterium murale DSM 22178(T) with 97.5 % and 97.4 % sequence similarities, respectively; while the DNA-DNA hybridization values were 33.1±3.4 % and 21.8±1.6 %, respectively. 25253073 2 48 theme Gram-staining-positive 88:109 arg1 bacterium 132:140 A Gram-staining-positive, rod-shaped, aerobic bacterium 86:140 A Gram-staining-positive, rod-shaped, aerobic bacterium 86:140 A Gram-staining-positive, rod-shaped, aerobic bacterium, designated strain LAM0410(T), was isolated from an oil-contaminated water sample from the Dagang Oilfield, PR China. 25253073 3 49 theme pH 280:281 arg1 °C 317:318 4 °C to 50 °C 306:318 4 °C to 50 °C 306:318 The temperature and pH ranges for growth were 4 °C to 50 °C and pH 4.4 to pH 12.0, respectively. 25253073 3 49 theme pH 280:281 arg1 ranges 283:288 The temperature and pH ranges 260:288 ranges 283:288 The temperature and pH ranges for growth were 4 °C to 50 °C and pH 4.4 to pH 12.0, respectively. 25253073 2 50 theme water 211:215 arg1 sample 217:222 an oil-contaminated water sample 191:222 an oil-contaminated water sample from the Dagang Oilfield, PR China 191:257 A Gram-staining-positive, rod-shaped, aerobic bacterium, designated strain LAM0410(T), was isolated from an oil-contaminated water sample from the Dagang Oilfield, PR China. 25253073 13 51 theme Microbacterium 1420:1433 arg1 species 1399:1405 a novel species 1391:1405 a novel species 1391:1405 Based on its phenotypic and genotypic properties, strain LAM0410(T) represents a novel species of the genus Microbacterium, for which the name Microbacterium petrolearium sp. 25253073 4 52 theme % 445:445 arg1 concentration 419:431 a concentration 417:431 a concentration of up to 12 % (w/v) 417:451 The strain did not need NaCl for growth, but could tolerate a concentration of up to 12 % (w/v). 25253073 13 53 theme genus 1414:1418 arg1 Microbacterium 1420:1433 the genus Microbacterium 1410:1433 the genus Microbacterium 1410:1433 Based on its phenotypic and genotypic properties, strain LAM0410(T) represents a novel species of the genus Microbacterium, for which the name Microbacterium petrolearium sp. 25253073 2 54 theme oil-contaminated 194:209 arg1 sample 217:222 an oil-contaminated water sample 191:222 an oil-contaminated water sample from the Dagang Oilfield, PR China 191:257 A Gram-staining-positive, rod-shaped, aerobic bacterium, designated strain LAM0410(T), was isolated from an oil-contaminated water sample from the Dagang Oilfield, PR China. 25253073 11 55 theme 16S 897:899 arg1 analysis 920:927 16S rRNA gene sequence analysis 897:927 16S rRNA gene sequence analysis 897:927 16S rRNA gene sequence analysis indicated that the isolate belonged to the genus Microbacterium and was closely related to Microbacterium sediminis MCCC 1A06153(T) and Microbacterium murale DSM 22178(T) with 97.5 % and 97.4 % sequence similarities, respectively; while the DNA-DNA hybridization values were 33.1±3.4 % and 21.8±1.6 %, respectively. 25253073 2 56 from China 253:257 arg1 sample 217:222 an oil-contaminated water sample 191:222 an oil-contaminated water sample from the Dagang Oilfield, PR China 191:257 A Gram-staining-positive, rod-shaped, aerobic bacterium, designated strain LAM0410(T), was isolated from an oil-contaminated water sample from the Dagang Oilfield, PR China. 25253073 13 57 theme genotypic 1340:1348 arg1 properties 1350:1359 its phenotypic and genotypic properties 1321:1359 its phenotypic and genotypic properties 1321:1359 Based on its phenotypic and genotypic properties, strain LAM0410(T) represents a novel species of the genus Microbacterium, for which the name Microbacterium petrolearium sp. 25253073 3 58 theme temperature 264:274 arg1 °C 317:318 4 °C to 50 °C 306:318 4 °C to 50 °C 306:318 The temperature and pH ranges for growth were 4 °C to 50 °C and pH 4.4 to pH 12.0, respectively. 25253073 3 58 theme temperature 264:274 arg1 ranges 283:288 The temperature and pH ranges 260:288 ranges 283:288 The temperature and pH ranges for growth were 4 °C to 50 °C and pH 4.4 to pH 12.0, respectively. 25253073 11 59 theme Microbacterium 1020:1033 arg1 MCCC 1045:1048 Microbacterium sediminis MCCC 1A06153 1020:1056 Microbacterium sediminis MCCC 1A06153(T) 1020:1059 16S rRNA gene sequence analysis indicated that the isolate belonged to the genus Microbacterium and was closely related to Microbacterium sediminis MCCC 1A06153(T) and Microbacterium murale DSM 22178(T) with 97.5 % and 97.4 % sequence similarities, respectively; while the DNA-DNA hybridization values were 33.1±3.4 % and 21.8±1.6 %, respectively. 25253073 11 59 theme Microbacterium 1020:1033 arg1 T 1058:1058 T 1058:1058 T 1058:1058 16S rRNA gene sequence analysis indicated that the isolate belonged to the genus Microbacterium and was closely related to Microbacterium sediminis MCCC 1A06153(T) and Microbacterium murale DSM 22178(T) with 97.5 % and 97.4 % sequence similarities, respectively; while the DNA-DNA hybridization values were 33.1±3.4 % and 21.8±1.6 %, respectively. 25253073 10 60 dep anteiso-C15  847:858 arg1  0 877:878  0 877:878  0 877:878 The major fatty acids were anteiso-C15 : 0, anteiso-C17 : 0 and iso-C16 : 0. 25253073 10 60 dep anteiso-C15  847:858 arg1 iso-C16  884:891 iso-C16  884:891 iso-C16  884:891 The major fatty acids were anteiso-C15 : 0, anteiso-C17 : 0 and iso-C16 : 0. 25253073 10 60 dep anteiso-C15  847:858 arg1  0 893:894  0 893:894  0 893:894 The major fatty acids were anteiso-C15 : 0, anteiso-C17 : 0 and iso-C16 : 0. 25253073 10 60 dep anteiso-C15  847:858 arg1  0 860:861  0 860:861  0 860:861 The major fatty acids were anteiso-C15 : 0, anteiso-C17 : 0 and iso-C16 : 0. 25253073 3 61 dep °C 317:318 arg1 to 311:312 to 311:312 to 311:312 The temperature and pH ranges for growth were 4 °C to 50 °C and pH 4.4 to pH 12.0, respectively. 25253073 12 62 theme Tm 1301:1302 arg1 method 1304:1309 the Tm method 1297:1309 the Tm method 1297:1309 The DNA G+C content was 67.4 mol%, as determined by the Tm method. 25253073 2 63 theme Oilfield 240:247 arg1 China 253:257 the Dagang Oilfield, PR China 229:257 China 253:257 A Gram-staining-positive, rod-shaped, aerobic bacterium, designated strain LAM0410(T), was isolated from an oil-contaminated water sample from the Dagang Oilfield, PR China. 25253073 7 64 theme N-glycolyl 636:645 arg1 residues 647:654 N-glycolyl residues 636:654 N-glycolyl residues 636:654 The glycan moiety of the cell wall contained N-glycolyl residues. 25253073 11 65 with related 1009:1015 arg1 similarities 1132:1143 97.4 % sequence similarities 1116:1143 97.4 % sequence similarities 1116:1143 16S rRNA gene sequence analysis indicated that the isolate belonged to the genus Microbacterium and was closely related to Microbacterium sediminis MCCC 1A06153(T) and Microbacterium murale DSM 22178(T) with 97.5 % and 97.4 % sequence similarities, respectively; while the DNA-DNA hybridization values were 33.1±3.4 % and 21.8±1.6 %, respectively. 25253073 11 65 with related 1009:1015 arg1 % 1110:1110 97.5 % 1105:1110 97.5 % 1105:1110 16S rRNA gene sequence analysis indicated that the isolate belonged to the genus Microbacterium and was closely related to Microbacterium sediminis MCCC 1A06153(T) and Microbacterium murale DSM 22178(T) with 97.5 % and 97.4 % sequence similarities, respectively; while the DNA-DNA hybridization values were 33.1±3.4 % and 21.8±1.6 %, respectively. 25253073 2 66 theme Dagang 233:238 arg1 China 253:257 the Dagang Oilfield, PR China 229:257 China 253:257 A Gram-staining-positive, rod-shaped, aerobic bacterium, designated strain LAM0410(T), was isolated from an oil-contaminated water sample from the Dagang Oilfield, PR China. 25253073 14 67 theme type 1509:1512 arg1 strain 1514:1519 the type strain 1505:1519 the type strain 1505:1519 nov. is proposed; the type strain is LAM0410(T) ( = ACCC 00719(T) = JCM 19612(T)). 25253073 14 67 theme type 1509:1512 arg1 LAM0410 1524:1530 LAM0410 1524:1530 LAM0410(T) ( = ACCC 00719(T) = JCM 19612(T)) 1524:1567 nov. is proposed; the type strain is LAM0410(T) ( = ACCC 00719(T) = JCM 19612(T)). 25253073 2 68 dep China 253:257 arg1 PR 250:251 the Dagang Oilfield, PR China 229:257 PR 250:251 A Gram-staining-positive, rod-shaped, aerobic bacterium, designated strain LAM0410(T), was isolated from an oil-contaminated water sample from the Dagang Oilfield, PR China. 25253073 7 69 theme cell 616:619 arg1 wall 621:624 the cell wall 612:624 the cell wall 612:624 The glycan moiety of the cell wall contained N-glycolyl residues. 25253073 13 70 dep Microbacterium 1455:1468 arg1 petrolearium 1470:1481 petrolearium 1470:1481 petrolearium 1470:1481 Based on its phenotypic and genotypic properties, strain LAM0410(T) represents a novel species of the genus Microbacterium, for which the name Microbacterium petrolearium sp. 25253073 7 71 contain contained 626:634 arg2 residues 647:654 N-glycolyl residues 636:654 N-glycolyl residues 636:654 The glycan moiety of the cell wall contained N-glycolyl residues. 25253073 7 71 contain contained 626:634 arg1 moiety 602:607 The glycan moiety 591:607 The glycan moiety of the cell wall 591:624 The glycan moiety of the cell wall contained N-glycolyl residues. 25253073 11 72 theme DNA-DNA 1170:1176 arg1 values 1192:1197 the DNA-DNA hybridization values 1166:1197 the DNA-DNA hybridization values 1166:1197 16S rRNA gene sequence analysis indicated that the isolate belonged to the genus Microbacterium and was closely related to Microbacterium sediminis MCCC 1A06153(T) and Microbacterium murale DSM 22178(T) with 97.5 % and 97.4 % sequence similarities, respectively; while the DNA-DNA hybridization values were 33.1±3.4 % and 21.8±1.6 %, respectively. 25253073 11 72 theme DNA-DNA 1170:1176 arg1 % 1213:1213 33.1±3.4 % 1204:1213 33.1±3.4 % 1204:1213 16S rRNA gene sequence analysis indicated that the isolate belonged to the genus Microbacterium and was closely related to Microbacterium sediminis MCCC 1A06153(T) and Microbacterium murale DSM 22178(T) with 97.5 % and 97.4 % sequence similarities, respectively; while the DNA-DNA hybridization values were 33.1±3.4 % and 21.8±1.6 %, respectively. 25253073 7 73 theme wall 621:624 arg1 moiety 602:607 The glycan moiety 591:607 The glycan moiety of the cell wall 591:624 The glycan moiety of the cell wall contained N-glycolyl residues. 29057827 10 0 from SVR 1433:1435 arg1 patients 1444:1451 CHC patients 1440:1451 CHC patients undergoing IFN-free DAAs therapy 1440:1484 CONCLUSION Pretreatment BTR level can be helpful for predicting increased SMI after SVR in CHC patients undergoing IFN-free DAAs therapy. 29057827 5 1 from SVR 776:778 arg1 SMI 769:771 the increased SMI 755:771 the increased SMI at SVR 755:778 Further, we identified pretreatment parameters contributing to the increased SMI at SVR. 29057827 4 2 theme mass 620:623 arg1 SMI 571:573 SMI 571:573 SMI 571:573 SMI was calculated as the sum of skeletal muscle mass in upper and lower extremities divided by height squared (cm²/m²). 29057827 4 2 theme mass 620:623 arg1 sum 597:599 the sum 593:599 the sum of skeletal muscle mass in upper and lower extremities divided by height squared (cm²/m²) 593:689 SMI was calculated as the sum of skeletal muscle mass in upper and lower extremities divided by height squared (cm²/m²). 29057827 0 3 theme Virological 76:86 arg1 Response 88:95 Sustained Virological Response 66:95 Sustained Virological Response in Chronic Hepatitis C 66:118 Predictors Associated with Increase in Skeletal Muscle Mass after Sustained Virological Response in Chronic Hepatitis C Treated with Direct Acting Antivirals. 29057827 8 4 theme univariate 1026:1035 arg1 analysis 1037:1044 the univariate analysis 1022:1044 the univariate analysis 1022:1044 In the univariate analysis, age (p = 0.0392), hyaluronic acid (p = 0.0143), and branched-chain amino acid to tyrosine ratio (BTR) (p = 0.0024) were significant pretreatment factors linked to increased SMI at SVR. 29057827 4 5 theme muscle 613:618 arg1 mass 620:623 skeletal muscle mass 604:623 skeletal muscle mass 604:623 SMI was calculated as the sum of skeletal muscle mass in upper and lower extremities divided by height squared (cm²/m²). 29057827 1 6 theme virological 350:360 arg1 SVR 372:374 SVR 372:374 SVR 372:374 AIMS We aimed to examine changes in skeletal muscle mass in chronic hepatitis C (CHC) patients undergoing interferon (IFN)-free direct acting antivirals (DAAs) therapy who achieved sustained virological response (SVR). 29057827 1 6 theme virological 350:360 arg1 response 362:369 sustained virological response 340:369 sustained virological response (SVR) 340:375 AIMS We aimed to examine changes in skeletal muscle mass in chronic hepatitis C (CHC) patients undergoing interferon (IFN)-free direct acting antivirals (DAAs) therapy who achieved sustained virological response (SVR). 29057827 0 7 theme Chronic 100:106 arg1 C 118:118 Chronic Hepatitis C 100:118 Chronic Hepatitis C 100:118 Predictors Associated with Increase in Skeletal Muscle Mass after Sustained Virological Response in Chronic Hepatitis C Treated with Direct Acting Antivirals. 29057827 8 8 theme = 1152:1152 arg1 0.0024 1154:1159 p = 0.0024 1150:1159 p = 0.0024 1150:1159 In the univariate analysis, age (p = 0.0392), hyaluronic acid (p = 0.0143), and branched-chain amino acid to tyrosine ratio (BTR) (p = 0.0024) were significant pretreatment factors linked to increased SMI at SVR. 29057827 8 8 theme = 1152:1152 arg1 acid 1120:1123 branched-chain amino acid 1099:1123 branched-chain amino acid to tyrosine ratio (BTR) (p = 0.0024) 1099:1160 In the univariate analysis, age (p = 0.0392), hyaluronic acid (p = 0.0143), and branched-chain amino acid to tyrosine ratio (BTR) (p = 0.0024) were significant pretreatment factors linked to increased SMI at SVR. 29057827 8 9 theme p 1150:1150 arg1 0.0024 1154:1159 p = 0.0024 1150:1159 p = 0.0024 1150:1159 In the univariate analysis, age (p = 0.0392), hyaluronic acid (p = 0.0143), and branched-chain amino acid to tyrosine ratio (BTR) (p = 0.0024) were significant pretreatment factors linked to increased SMI at SVR. 29057827 8 9 theme p 1150:1150 arg1 acid 1120:1123 branched-chain amino acid 1099:1123 branched-chain amino acid to tyrosine ratio (BTR) (p = 0.0024) 1099:1160 In the univariate analysis, age (p = 0.0392), hyaluronic acid (p = 0.0143), and branched-chain amino acid to tyrosine ratio (BTR) (p = 0.0024) were significant pretreatment factors linked to increased SMI at SVR. 29057827 3 10 theme skeletal 486:493 arg1 muscle 495:500 skeletal muscle index (SMI) 486:512 skeletal muscle index (SMI) 486:512 We compared the changes in skeletal muscle index (SMI) using bio-impedance analysis at baseline and SMI at SVR. 29057827 10 11 theme DAAs 1473:1476 arg1 therapy 1478:1484 IFN-free DAAs therapy 1464:1484 IFN-free DAAs therapy 1464:1484 CONCLUSION Pretreatment BTR level can be helpful for predicting increased SMI after SVR in CHC patients undergoing IFN-free DAAs therapy. 29057827 6 12 from SMI 789:791 arg1 males 796:800 males 796:800 males 796:800 RESULTS SMI in males at baseline ranged from 6.73 to 9.08 cm²/m² (median, 7.65 cm²/m²), while that in females ranged from 4.45 to 7.27 cm²/m² (median, 5.81 cm²/m²). 29057827 4 13 from sum 597:599 arg1 extremities 644:654 upper and lower extremities 628:654 upper and lower extremities divided by height squared (cm²/m²) 628:689 SMI was calculated as the sum of skeletal muscle mass in upper and lower extremities divided by height squared (cm²/m²). 29057827 10 14 theme increased 1413:1421 arg1 SMI 1423:1425 increased SMI 1413:1425 increased SMI 1413:1425 CONCLUSION Pretreatment BTR level can be helpful for predicting increased SMI after SVR in CHC patients undergoing IFN-free DAAs therapy. 29057827 8 15 theme = 1054:1054 arg1 p 1052:1052 p = 0.0392 1052:1061 p = 0.0392 1052:1061 In the univariate analysis, age (p = 0.0392), hyaluronic acid (p = 0.0143), and branched-chain amino acid to tyrosine ratio (BTR) (p = 0.0024) were significant pretreatment factors linked to increased SMI at SVR. 29057827 8 15 theme = 1054:1054 arg1 age 1047:1049 age 1047:1049 age (p = 0.0392) 1047:1062 In the univariate analysis, age (p = 0.0392), hyaluronic acid (p = 0.0143), and branched-chain amino acid to tyrosine ratio (BTR) (p = 0.0024) were significant pretreatment factors linked to increased SMI at SVR. 29057827 9 16 theme independent 1278:1288 arg1 BTR 1267:1269 only BTR 1262:1269 only BTR 1262:1269 In the multivariate analysis, only BTR was an independent predictor linked to the increased SMI at SVR (p = 0.0488). 29057827 9 16 theme independent 1278:1288 arg1 predictor 1290:1298 an independent predictor 1275:1298 an independent predictor linked to the increased SMI 1275:1326 In the multivariate analysis, only BTR was an independent predictor linked to the increased SMI at SVR (p = 0.0488). 29057827 0 17 theme Hepatitis 108:116 arg1 C 118:118 Chronic Hepatitis C 100:118 Chronic Hepatitis C 100:118 Predictors Associated with Increase in Skeletal Muscle Mass after Sustained Virological Response in Chronic Hepatitis C Treated with Direct Acting Antivirals. 29057827 9 18 theme multivariate 1239:1250 arg1 analysis 1252:1259 the multivariate analysis 1235:1259 the multivariate analysis 1235:1259 In the multivariate analysis, only BTR was an independent predictor linked to the increased SMI at SVR (p = 0.0488). 29057827 6 19 dep 7.27 911:914 arg1 to 908:909 to 908:909 to 908:909 RESULTS SMI in males at baseline ranged from 6.73 to 9.08 cm²/m² (median, 7.65 cm²/m²), while that in females ranged from 4.45 to 7.27 cm²/m² (median, 5.81 cm²/m²). 29057827 10 20 theme CONCLUSION 1349:1358 arg1 level 1377:1381 CONCLUSION Pretreatment BTR level 1349:1381 CONCLUSION Pretreatment BTR level 1349:1381 CONCLUSION Pretreatment BTR level can be helpful for predicting increased SMI after SVR in CHC patients undergoing IFN-free DAAs therapy. 29057827 10 21 theme IFN-free 1464:1471 arg1 therapy 1478:1484 IFN-free DAAs therapy 1464:1484 IFN-free DAAs therapy 1464:1484 CONCLUSION Pretreatment BTR level can be helpful for predicting increased SMI after SVR in CHC patients undergoing IFN-free DAAs therapy. 29057827 1 22 theme sustained 340:348 arg1 SVR 372:374 SVR 372:374 SVR 372:374 AIMS We aimed to examine changes in skeletal muscle mass in chronic hepatitis C (CHC) patients undergoing interferon (IFN)-free direct acting antivirals (DAAs) therapy who achieved sustained virological response (SVR). 29057827 1 22 theme sustained 340:348 arg1 response 362:369 sustained virological response 340:369 sustained virological response (SVR) 340:375 AIMS We aimed to examine changes in skeletal muscle mass in chronic hepatitis C (CHC) patients undergoing interferon (IFN)-free direct acting antivirals (DAAs) therapy who achieved sustained virological response (SVR). 29057827 7 23 contain had 974:976 arg1 % 971:971 52.2% 967:971 52.2% 967:971 At SVR, 36 patients (52.2%) had increased SMI as compared with baseline. 29057827 7 23 contain had 974:976 arg2 SMI 988:990 increased SMI 978:990 increased SMI 978:990 At SVR, 36 patients (52.2%) had increased SMI as compared with baseline. 29057827 7 23 contain had 974:976 arg1 patients 957:964 36 patients 954:964 36 patients (52.2%) 954:972 At SVR, 36 patients (52.2%) had increased SMI as compared with baseline. 29057827 1 24 dep AIMS 159:162 arg1 aimed 167:171 aimed 167:171 aimed to examine changes in skeletal muscle mass in chronic hepatitis C (CHC) patients undergoing interferon (IFN)-free direct acting antivirals (DAAs) therapy who achieved sustained virological response (SVR) 167:375 AIMS We aimed to examine changes in skeletal muscle mass in chronic hepatitis C (CHC) patients undergoing interferon (IFN)-free direct acting antivirals (DAAs) therapy who achieved sustained virological response (SVR). 29057827 6 25 dep 9.08 834:837 arg1 to 831:832 to 831:832 to 831:832 RESULTS SMI in males at baseline ranged from 6.73 to 9.08 cm²/m² (median, 7.65 cm²/m²), while that in females ranged from 4.45 to 7.27 cm²/m² (median, 5.81 cm²/m²). 29057827 5 26 theme pretreatment 715:726 arg1 parameters 728:737 pretreatment parameters 715:737 pretreatment parameters contributing to the increased SMI at SVR 715:778 Further, we identified pretreatment parameters contributing to the increased SMI at SVR. 29057827 6 27 dep ranged 891:896 arg1 median 924:929 median 924:929 median 924:929 RESULTS SMI in males at baseline ranged from 6.73 to 9.08 cm²/m² (median, 7.65 cm²/m²), while that in females ranged from 4.45 to 7.27 cm²/m² (median, 5.81 cm²/m²). 29057827 6 27 dep ranged 891:896 arg1 cm²/m² 937:942 5.81 cm²/m² 932:942 5.81 cm²/m² 932:942 RESULTS SMI in males at baseline ranged from 6.73 to 9.08 cm²/m² (median, 7.65 cm²/m²), while that in females ranged from 4.45 to 7.27 cm²/m² (median, 5.81 cm²/m²). 29057827 8 28 theme significant 1167:1177 arg1 factors 1192:1198 significant pretreatment factors 1167:1198 significant pretreatment factors linked to increased SMI at SVR 1167:1229 In the univariate analysis, age (p = 0.0392), hyaluronic acid (p = 0.0143), and branched-chain amino acid to tyrosine ratio (BTR) (p = 0.0024) were significant pretreatment factors linked to increased SMI at SVR. 29057827 10 29 theme Pretreatment 1360:1371 arg1 level 1377:1381 CONCLUSION Pretreatment BTR level 1349:1381 CONCLUSION Pretreatment BTR level 1349:1381 CONCLUSION Pretreatment BTR level can be helpful for predicting increased SMI after SVR in CHC patients undergoing IFN-free DAAs therapy. 29057827 3 30 theme bio-impedance 520:532 arg1 analysis 534:541 bio-impedance analysis 520:541 bio-impedance analysis 520:541 We compared the changes in skeletal muscle index (SMI) using bio-impedance analysis at baseline and SMI at SVR. 29057827 4 31 theme height 667:672 arg1 cm²/m² 683:688 cm²/m² 683:688 cm²/m² 683:688 SMI was calculated as the sum of skeletal muscle mass in upper and lower extremities divided by height squared (cm²/m²). 29057827 4 31 theme height 667:672 arg1 squared 674:680 height squared 667:680 height squared (cm²/m²) 667:689 SMI was calculated as the sum of skeletal muscle mass in upper and lower extremities divided by height squared (cm²/m²). 29057827 9 32 from SVR 1331:1333 arg1 BTR 1267:1269 only BTR 1262:1269 only BTR 1262:1269 In the multivariate analysis, only BTR was an independent predictor linked to the increased SMI at SVR (p = 0.0488). 29057827 9 32 from SVR 1331:1333 arg1 predictor 1290:1298 an independent predictor 1275:1298 an independent predictor linked to the increased SMI 1275:1326 In the multivariate analysis, only BTR was an independent predictor linked to the increased SMI at SVR (p = 0.0488). 29057827 7 33 theme increased 978:986 arg1 SMI 988:990 increased SMI 978:990 increased SMI 978:990 At SVR, 36 patients (52.2%) had increased SMI as compared with baseline. 29057827 10 34 theme CHC 1440:1442 arg1 patients 1444:1451 CHC patients 1440:1451 CHC patients undergoing IFN-free DAAs therapy 1440:1484 CONCLUSION Pretreatment BTR level can be helpful for predicting increased SMI after SVR in CHC patients undergoing IFN-free DAAs therapy. 29057827 0 35 from Response 88:95 arg1 C 118:118 Chronic Hepatitis C 100:118 Chronic Hepatitis C 100:118 Predictors Associated with Increase in Skeletal Muscle Mass after Sustained Virological Response in Chronic Hepatitis C Treated with Direct Acting Antivirals. 29057827 9 36 theme only 1262:1265 arg1 BTR 1267:1269 only BTR 1262:1269 only BTR 1262:1269 In the multivariate analysis, only BTR was an independent predictor linked to the increased SMI at SVR (p = 0.0488). 29057827 9 36 theme only 1262:1265 arg1 predictor 1290:1298 an independent predictor 1275:1298 an independent predictor linked to the increased SMI 1275:1326 In the multivariate analysis, only BTR was an independent predictor linked to the increased SMI at SVR (p = 0.0488). 29057827 1 37 theme skeletal 195:202 arg1 mass 211:214 skeletal muscle mass 195:214 skeletal muscle mass 195:214 AIMS We aimed to examine changes in skeletal muscle mass in chronic hepatitis C (CHC) patients undergoing interferon (IFN)-free direct acting antivirals (DAAs) therapy who achieved sustained virological response (SVR). 29057827 0 38 theme Skeletal 39:46 arg1 Mass 55:58 Skeletal Muscle Mass 39:58 Skeletal Muscle Mass 39:58 Predictors Associated with Increase in Skeletal Muscle Mass after Sustained Virological Response in Chronic Hepatitis C Treated with Direct Acting Antivirals. 29057827 0 39 theme Acting 140:145 arg1 Antivirals 147:156 Direct Acting Antivirals 133:156 Direct Acting Antivirals 133:156 Predictors Associated with Increase in Skeletal Muscle Mass after Sustained Virological Response in Chronic Hepatitis C Treated with Direct Acting Antivirals. 29057827 5 40 theme increased 759:767 arg1 SMI 769:771 the increased SMI 755:771 the increased SMI at SVR 755:778 Further, we identified pretreatment parameters contributing to the increased SMI at SVR. 29057827 9 41 theme increased 1314:1322 arg1 SMI 1324:1326 the increased SMI 1310:1326 the increased SMI 1310:1326 In the multivariate analysis, only BTR was an independent predictor linked to the increased SMI at SVR (p = 0.0488). 29057827 1 42 theme muscle 204:209 arg1 mass 211:214 skeletal muscle mass 195:214 skeletal muscle mass 195:214 AIMS We aimed to examine changes in skeletal muscle mass in chronic hepatitis C (CHC) patients undergoing interferon (IFN)-free direct acting antivirals (DAAs) therapy who achieved sustained virological response (SVR). 29057827 2 43 theme patients 417:424 arg1 total 401:405 A total 399:405 PATIENTS AND METHODS A total of 69 CHC patients treated with DAAs 378:442 PATIENTS AND METHODS A total of 69 CHC patients treated with DAAs were analyzed. 29057827 0 44 theme Direct 133:138 arg1 Antivirals 147:156 Direct Acting Antivirals 133:156 Direct Acting Antivirals 133:156 Predictors Associated with Increase in Skeletal Muscle Mass after Sustained Virological Response in Chronic Hepatitis C Treated with Direct Acting Antivirals. 29057827 8 45 from factors 1192:1198 arg1 analysis 1037:1044 the univariate analysis 1022:1044 the univariate analysis 1022:1044 In the univariate analysis, age (p = 0.0392), hyaluronic acid (p = 0.0143), and branched-chain amino acid to tyrosine ratio (BTR) (p = 0.0024) were significant pretreatment factors linked to increased SMI at SVR. 29057827 10 46 theme BTR 1373:1375 arg1 level 1377:1381 CONCLUSION Pretreatment BTR level 1349:1381 CONCLUSION Pretreatment BTR level 1349:1381 CONCLUSION Pretreatment BTR level can be helpful for predicting increased SMI after SVR in CHC patients undergoing IFN-free DAAs therapy. 29057827 2 47 theme CHC 413:415 arg1 patients 417:424 69 CHC patients 410:424 69 CHC patients treated with DAAs 410:442 PATIENTS AND METHODS A total of 69 CHC patients treated with DAAs were analyzed. 29057827 1 48 theme -free 281:285 arg1 therapy 319:325 interferon (IFN)-free direct acting antivirals (DAAs) therapy 265:325 interferon (IFN)-free direct acting antivirals (DAAs) therapy 265:325 AIMS We aimed to examine changes in skeletal muscle mass in chronic hepatitis C (CHC) patients undergoing interferon (IFN)-free direct acting antivirals (DAAs) therapy who achieved sustained virological response (SVR). 29057827 8 49 theme tyrosine 1128:1135 arg1 ratio 1137:1141 tyrosine ratio 1128:1141 tyrosine ratio 1128:1141 In the univariate analysis, age (p = 0.0392), hyaluronic acid (p = 0.0143), and branched-chain amino acid to tyrosine ratio (BTR) (p = 0.0024) were significant pretreatment factors linked to increased SMI at SVR. 29057827 6 50 dep cm²/m² 839:844 arg1 median 847:852 median 847:852 median 847:852 RESULTS SMI in males at baseline ranged from 6.73 to 9.08 cm²/m² (median, 7.65 cm²/m²), while that in females ranged from 4.45 to 7.27 cm²/m² (median, 5.81 cm²/m²). 29057827 6 50 dep cm²/m² 839:844 arg1 cm²/m² 860:865 7.65 cm²/m² 855:865 7.65 cm²/m² 855:865 RESULTS SMI in males at baseline ranged from 6.73 to 9.08 cm²/m² (median, 7.65 cm²/m²), while that in females ranged from 4.45 to 7.27 cm²/m² (median, 5.81 cm²/m²). 29057827 6 51 theme RESULTS 781:787 arg1 SMI 789:791 RESULTS SMI 781:791 RESULTS SMI in males at baseline 781:812 RESULTS SMI in males at baseline ranged from 6.73 to 9.08 cm²/m² (median, 7.65 cm²/m²), while that in females ranged from 4.45 to 7.27 cm²/m² (median, 5.81 cm²/m²). 29057827 4 52 theme upper 628:632 arg1 extremities 644:654 upper and lower extremities 628:654 upper and lower extremities divided by height squared (cm²/m²) 628:689 SMI was calculated as the sum of skeletal muscle mass in upper and lower extremities divided by height squared (cm²/m²). 29057827 0 53 theme Muscle 48:53 arg1 Mass 55:58 Skeletal Muscle Mass 39:58 Skeletal Muscle Mass 39:58 Predictors Associated with Increase in Skeletal Muscle Mass after Sustained Virological Response in Chronic Hepatitis C Treated with Direct Acting Antivirals. 29057827 1 54 theme direct 287:292 arg1 DAAs 313:316 DAAs 313:316 DAAs 313:316 AIMS We aimed to examine changes in skeletal muscle mass in chronic hepatitis C (CHC) patients undergoing interferon (IFN)-free direct acting antivirals (DAAs) therapy who achieved sustained virological response (SVR). 29057827 1 54 theme direct 287:292 arg1 antivirals 301:310 direct acting antivirals 287:310 interferon (IFN)-free direct acting antivirals (DAAs) therapy 265:325 AIMS We aimed to examine changes in skeletal muscle mass in chronic hepatitis C (CHC) patients undergoing interferon (IFN)-free direct acting antivirals (DAAs) therapy who achieved sustained virological response (SVR). 29057827 1 55 theme antivirals 301:310 arg1 therapy 319:325 interferon (IFN)-free direct acting antivirals (DAAs) therapy 265:325 interferon (IFN)-free direct acting antivirals (DAAs) therapy 265:325 AIMS We aimed to examine changes in skeletal muscle mass in chronic hepatitis C (CHC) patients undergoing interferon (IFN)-free direct acting antivirals (DAAs) therapy who achieved sustained virological response (SVR). 29057827 8 56 theme increased 1210:1218 arg1 SMI 1220:1222 increased SMI 1210:1222 increased SMI at SVR 1210:1229 In the univariate analysis, age (p = 0.0392), hyaluronic acid (p = 0.0143), and branched-chain amino acid to tyrosine ratio (BTR) (p = 0.0024) were significant pretreatment factors linked to increased SMI at SVR. 29057827 2 57 dep PATIENTS 378:385 arg1 total 401:405 A total 399:405 PATIENTS AND METHODS A total of 69 CHC patients treated with DAAs 378:442 PATIENTS AND METHODS A total of 69 CHC patients treated with DAAs were analyzed. 29057827 8 58 theme hyaluronic 1065:1074 arg1 p 1082:1082 p = 0.0143 1082:1091 p = 0.0143 1082:1091 In the univariate analysis, age (p = 0.0392), hyaluronic acid (p = 0.0143), and branched-chain amino acid to tyrosine ratio (BTR) (p = 0.0024) were significant pretreatment factors linked to increased SMI at SVR. 29057827 8 58 theme hyaluronic 1065:1074 arg1 acid 1076:1079 hyaluronic acid 1065:1079 hyaluronic acid (p = 0.0143) 1065:1092 In the univariate analysis, age (p = 0.0392), hyaluronic acid (p = 0.0143), and branched-chain amino acid to tyrosine ratio (BTR) (p = 0.0024) were significant pretreatment factors linked to increased SMI at SVR. 29057827 3 59 from SVR 566:568 arg1 SMI 559:561 SMI 559:561 SMI 559:561 We compared the changes in skeletal muscle index (SMI) using bio-impedance analysis at baseline and SMI at SVR. 29057827 3 59 from SVR 566:568 arg1 baseline 546:553 baseline 546:553 baseline 546:553 We compared the changes in skeletal muscle index (SMI) using bio-impedance analysis at baseline and SMI at SVR. 29057827 1 60 theme acting 294:299 arg1 DAAs 313:316 DAAs 313:316 DAAs 313:316 AIMS We aimed to examine changes in skeletal muscle mass in chronic hepatitis C (CHC) patients undergoing interferon (IFN)-free direct acting antivirals (DAAs) therapy who achieved sustained virological response (SVR). 29057827 1 60 theme acting 294:299 arg1 antivirals 301:310 direct acting antivirals 287:310 interferon (IFN)-free direct acting antivirals (DAAs) therapy 265:325 AIMS We aimed to examine changes in skeletal muscle mass in chronic hepatitis C (CHC) patients undergoing interferon (IFN)-free direct acting antivirals (DAAs) therapy who achieved sustained virological response (SVR). 29057827 9 61 attach linked 1300:1305 arg2 BTR 1267:1269 only BTR 1262:1269 only BTR 1262:1269 In the multivariate analysis, only BTR was an independent predictor linked to the increased SMI at SVR (p = 0.0488). 29057827 9 61 attach linked 1300:1305 arg2 predictor 1290:1298 an independent predictor 1275:1298 an independent predictor linked to the increased SMI 1275:1326 In the multivariate analysis, only BTR was an independent predictor linked to the increased SMI at SVR (p = 0.0488). 29057827 9 61 attach linked 1300:1305 arg1 SMI 1324:1326 the increased SMI 1310:1326 the increased SMI 1310:1326 In the multivariate analysis, only BTR was an independent predictor linked to the increased SMI at SVR (p = 0.0488). 29057827 4 62 theme lower 638:642 arg1 extremities 644:654 upper and lower extremities 628:654 upper and lower extremities divided by height squared (cm²/m²) 628:689 SMI was calculated as the sum of skeletal muscle mass in upper and lower extremities divided by height squared (cm²/m²). 29057827 8 63 theme amino 1114:1118 arg1 0.0024 1154:1159 p = 0.0024 1150:1159 p = 0.0024 1150:1159 In the univariate analysis, age (p = 0.0392), hyaluronic acid (p = 0.0143), and branched-chain amino acid to tyrosine ratio (BTR) (p = 0.0024) were significant pretreatment factors linked to increased SMI at SVR. 29057827 8 63 theme amino 1114:1118 arg1 BTR 1144:1146 BTR 1144:1146 BTR 1144:1146 In the univariate analysis, age (p = 0.0392), hyaluronic acid (p = 0.0143), and branched-chain amino acid to tyrosine ratio (BTR) (p = 0.0024) were significant pretreatment factors linked to increased SMI at SVR. 29057827 8 63 theme amino 1114:1118 arg1 acid 1120:1123 branched-chain amino acid 1099:1123 branched-chain amino acid to tyrosine ratio (BTR) (p = 0.0024) 1099:1160 In the univariate analysis, age (p = 0.0392), hyaluronic acid (p = 0.0143), and branched-chain amino acid to tyrosine ratio (BTR) (p = 0.0024) were significant pretreatment factors linked to increased SMI at SVR. 29057827 8 64 theme pretreatment 1179:1190 arg1 factors 1192:1198 significant pretreatment factors 1167:1198 significant pretreatment factors linked to increased SMI at SVR 1167:1229 In the univariate analysis, age (p = 0.0392), hyaluronic acid (p = 0.0143), and branched-chain amino acid to tyrosine ratio (BTR) (p = 0.0024) were significant pretreatment factors linked to increased SMI at SVR. 29057827 8 65 theme branched-chain 1099:1112 arg1 0.0024 1154:1159 p = 0.0024 1150:1159 p = 0.0024 1150:1159 In the univariate analysis, age (p = 0.0392), hyaluronic acid (p = 0.0143), and branched-chain amino acid to tyrosine ratio (BTR) (p = 0.0024) were significant pretreatment factors linked to increased SMI at SVR. 29057827 8 65 theme branched-chain 1099:1112 arg1 BTR 1144:1146 BTR 1144:1146 BTR 1144:1146 In the univariate analysis, age (p = 0.0392), hyaluronic acid (p = 0.0143), and branched-chain amino acid to tyrosine ratio (BTR) (p = 0.0024) were significant pretreatment factors linked to increased SMI at SVR. 29057827 8 65 theme branched-chain 1099:1112 arg1 acid 1120:1123 branched-chain amino acid 1099:1123 branched-chain amino acid to tyrosine ratio (BTR) (p = 0.0024) 1099:1160 In the univariate analysis, age (p = 0.0392), hyaluronic acid (p = 0.0143), and branched-chain amino acid to tyrosine ratio (BTR) (p = 0.0024) were significant pretreatment factors linked to increased SMI at SVR. 29057827 3 66 dep muscle 495:500 arg1 SMI 509:511 SMI 509:511 SMI 509:511 We compared the changes in skeletal muscle index (SMI) using bio-impedance analysis at baseline and SMI at SVR. 29057827 3 66 dep muscle 495:500 arg1 index 502:506 index 502:506 skeletal muscle index (SMI) 486:512 We compared the changes in skeletal muscle index (SMI) using bio-impedance analysis at baseline and SMI at SVR. 29057827 9 67 from predictor 1290:1298 arg1 analysis 1252:1259 the multivariate analysis 1235:1259 the multivariate analysis 1235:1259 In the multivariate analysis, only BTR was an independent predictor linked to the increased SMI at SVR (p = 0.0488). 29057827 1 68 theme chronic 219:225 arg1 CHC 240:242 CHC 240:242 CHC 240:242 AIMS We aimed to examine changes in skeletal muscle mass in chronic hepatitis C (CHC) patients undergoing interferon (IFN)-free direct acting antivirals (DAAs) therapy who achieved sustained virological response (SVR). 29057827 1 68 theme chronic 219:225 arg1 C 237:237 chronic hepatitis C 219:237 chronic hepatitis C (CHC) patients undergoing interferon (IFN)-free direct acting antivirals (DAAs) therapy who achieved sustained virological response (SVR) 219:375 AIMS We aimed to examine changes in skeletal muscle mass in chronic hepatitis C (CHC) patients undergoing interferon (IFN)-free direct acting antivirals (DAAs) therapy who achieved sustained virological response (SVR). 29057827 0 69 theme Sustained 66:74 arg1 Response 88:95 Sustained Virological Response 66:95 Sustained Virological Response in Chronic Hepatitis C 66:118 Predictors Associated with Increase in Skeletal Muscle Mass after Sustained Virological Response in Chronic Hepatitis C Treated with Direct Acting Antivirals. 29057827 9 70 theme = 1338:1338 arg1 p 1336:1336 p = 0.0488 1336:1345 p = 0.0488 1336:1345 In the multivariate analysis, only BTR was an independent predictor linked to the increased SMI at SVR (p = 0.0488). 29057827 9 70 theme = 1338:1338 arg1 SVR 1331:1333 SVR 1331:1333 SVR (p = 0.0488) 1331:1346 In the multivariate analysis, only BTR was an independent predictor linked to the increased SMI at SVR (p = 0.0488). 29057827 1 71 from changes 184:190 arg1 mass 211:214 skeletal muscle mass 195:214 skeletal muscle mass 195:214 AIMS We aimed to examine changes in skeletal muscle mass in chronic hepatitis C (CHC) patients undergoing interferon (IFN)-free direct acting antivirals (DAAs) therapy who achieved sustained virological response (SVR). 29057827 1 71 from changes 184:190 arg1 patients 245:252 chronic hepatitis C (CHC) patients 219:252 chronic hepatitis C (CHC) patients undergoing interferon (IFN)-free direct acting antivirals (DAAs) therapy who achieved sustained virological response (SVR) 219:375 AIMS We aimed to examine changes in skeletal muscle mass in chronic hepatitis C (CHC) patients undergoing interferon (IFN)-free direct acting antivirals (DAAs) therapy who achieved sustained virological response (SVR). 29057827 4 72 theme skeletal 604:611 arg1 mass 620:623 skeletal muscle mass 604:623 skeletal muscle mass 604:623 SMI was calculated as the sum of skeletal muscle mass in upper and lower extremities divided by height squared (cm²/m²). 29057827 8 73 attach linked 1200:1205 arg1 SMI 1220:1222 increased SMI 1210:1222 increased SMI at SVR 1210:1229 In the univariate analysis, age (p = 0.0392), hyaluronic acid (p = 0.0143), and branched-chain amino acid to tyrosine ratio (BTR) (p = 0.0024) were significant pretreatment factors linked to increased SMI at SVR. 29057827 8 73 attach linked 1200:1205 arg2 factors 1192:1198 significant pretreatment factors 1167:1198 significant pretreatment factors linked to increased SMI at SVR 1167:1229 In the univariate analysis, age (p = 0.0392), hyaluronic acid (p = 0.0143), and branched-chain amino acid to tyrosine ratio (BTR) (p = 0.0024) were significant pretreatment factors linked to increased SMI at SVR. 29057827 1 74 theme hepatitis 227:235 arg1 CHC 240:242 CHC 240:242 CHC 240:242 AIMS We aimed to examine changes in skeletal muscle mass in chronic hepatitis C (CHC) patients undergoing interferon (IFN)-free direct acting antivirals (DAAs) therapy who achieved sustained virological response (SVR). 29057827 1 74 theme hepatitis 227:235 arg1 C 237:237 chronic hepatitis C 219:237 chronic hepatitis C (CHC) patients undergoing interferon (IFN)-free direct acting antivirals (DAAs) therapy who achieved sustained virological response (SVR) 219:375 AIMS We aimed to examine changes in skeletal muscle mass in chronic hepatitis C (CHC) patients undergoing interferon (IFN)-free direct acting antivirals (DAAs) therapy who achieved sustained virological response (SVR). 29057827 6 75 from baseline 805:812 arg1 SMI 789:791 RESULTS SMI 781:791 RESULTS SMI in males at baseline 781:812 RESULTS SMI in males at baseline ranged from 6.73 to 9.08 cm²/m² (median, 7.65 cm²/m²), while that in females ranged from 4.45 to 7.27 cm²/m² (median, 5.81 cm²/m²). 29057827 0 76 from Increase 27:34 arg1 Mass 55:58 Skeletal Muscle Mass 39:58 Skeletal Muscle Mass 39:58 Predictors Associated with Increase in Skeletal Muscle Mass after Sustained Virological Response in Chronic Hepatitis C Treated with Direct Acting Antivirals. 29057827 8 77 from SVR 1227:1229 arg1 SMI 1220:1222 increased SMI 1210:1222 increased SMI at SVR 1210:1229 In the univariate analysis, age (p = 0.0392), hyaluronic acid (p = 0.0143), and branched-chain amino acid to tyrosine ratio (BTR) (p = 0.0024) were significant pretreatment factors linked to increased SMI at SVR. 29057827 8 78 theme = 1084:1084 arg1 p 1082:1082 p = 0.0143 1082:1091 p = 0.0143 1082:1091 In the univariate analysis, age (p = 0.0392), hyaluronic acid (p = 0.0143), and branched-chain amino acid to tyrosine ratio (BTR) (p = 0.0024) were significant pretreatment factors linked to increased SMI at SVR. 29057827 8 78 theme = 1084:1084 arg1 acid 1076:1079 hyaluronic acid 1065:1079 hyaluronic acid (p = 0.0143) 1065:1092 In the univariate analysis, age (p = 0.0392), hyaluronic acid (p = 0.0143), and branched-chain amino acid to tyrosine ratio (BTR) (p = 0.0024) were significant pretreatment factors linked to increased SMI at SVR. 29057827 3 79 from changes 475:481 arg1 muscle 495:500 skeletal muscle index (SMI) 486:512 skeletal muscle index (SMI) 486:512 We compared the changes in skeletal muscle index (SMI) using bio-impedance analysis at baseline and SMI at SVR. 29057827 1 80 theme C 237:237 arg1 patients 245:252 chronic hepatitis C (CHC) patients 219:252 chronic hepatitis C (CHC) patients undergoing interferon (IFN)-free direct acting antivirals (DAAs) therapy who achieved sustained virological response (SVR) 219:375 AIMS We aimed to examine changes in skeletal muscle mass in chronic hepatitis C (CHC) patients undergoing interferon (IFN)-free direct acting antivirals (DAAs) therapy who achieved sustained virological response (SVR). 27554083 0 0 theme macrophage-mediated 72:90 arg1 clearance 92:100 macrophage-mediated clearance 72:100 macrophage-mediated clearance 72:100 N-linked glycans within the A2 domain of von Willebrand factor modulate macrophage-mediated clearance. 27554083 4 1 theme receptor-recognition 470:489 arg1 site 491:494 a receptor-recognition site 468:494 a receptor-recognition site that plays a key role in regulating the interaction of VWF with macrophages 468:570 Our findings demonstrate that the A1 domain of VWF contains a receptor-recognition site that plays a key role in regulating the interaction of VWF with macrophages. 27554083 11 2 theme domain 1654:1659 arg1 presence 1612:1619 the presence 1608:1619 the presence of a structurally constrained A2 domain 1608:1659 Finally, we further demonstrate that loss of these N-linked glycans does not enhance clearance in VWF in the presence of a structurally constrained A2 domain. 27554083 11 3 from clearance 1588:1596 arg1 VWF 1601:1603 VWF 1601:1603 VWF 1601:1603 Finally, we further demonstrate that loss of these N-linked glycans does not enhance clearance in VWF in the presence of a structurally constrained A2 domain. 27554083 6 4 theme important 799:807 arg1 role 809:812 an important role 796:812 an important role 796:812 Previous studies have demonstrated that the N-linked glycans within the A2 domain play an important role in modulating susceptibility to ADAMTS13 proteolysis. 27554083 5 5 from A1-A2-A3 576:583 arg1 cryptic 638:644 cryptic 638:644 cryptic 638:644 In A1-A2-A3 and full-length VWF, this macrophage-binding site is cryptic but becomes exposed following exposure to shear or ristocetin. 27554083 12 6 theme VWF 1745:1747 arg1 domains 1751:1757 the VWF A domains 1741:1757 the VWF A domains 1741:1757 Collectively, these novel findings support the hypothesis that conformation of the VWF A domains plays a critical role in modulating macrophage-mediated clearance of VWF in vivo. 27554083 4 7 theme VWF 551:553 arg1 interaction 536:546 the interaction 532:546 the interaction of VWF with macrophages 532:570 Our findings demonstrate that the A1 domain of VWF contains a receptor-recognition site that plays a key role in regulating the interaction of VWF with macrophages. 27554083 3 8 theme domains 338:344 arg1 role 326:329 the role 322:329 the role of VWF domains and specific glycan moieties in regulating in vivo clearance 322:405 In this study, we investigated the role of VWF domains and specific glycan moieties in regulating in vivo clearance. 27554083 9 9 theme enhanced 1311:1318 arg1 clearance 1320:1328 significantly enhanced clearance 1297:1328 significantly enhanced clearance 1297:1328 In addition, A1-A2-A3 fragments containing the N1515Q or N1574Q substitutions also demonstrated significantly enhanced clearance. 27554083 1 10 from important 153:161 arg1 etiology 170:177 the etiology 166:177 the etiology of von Willebrand disease 166:203 Enhanced von Willebrand factor (VWF) clearance is important in the etiology of von Willebrand disease. 27554083 11 11 theme N-linked 1554:1561 arg1 glycans 1563:1569 these N-linked glycans 1548:1569 these N-linked glycans 1548:1569 Finally, we further demonstrate that loss of these N-linked glycans does not enhance clearance in VWF in the presence of a structurally constrained A2 domain. 27554083 10 12 located observed 1433:1440 arg2 clearance 1423:1431 the increased clearance 1409:1431 the increased clearance observed with N1515Q and N1574Q in both full-length VWF and A1-A2-A3 1409:1500 Importantly, clodronate-induced macrophage depletion significantly attenuated the increased clearance observed with N1515Q and N1574Q in both full-length VWF and A1-A2-A3. 27554083 10 12 located observed 1433:1440 arg1 A1-A2-A3 1493:1500 A1-A2-A3 1493:1500 A1-A2-A3 1493:1500 Importantly, clodronate-induced macrophage depletion significantly attenuated the increased clearance observed with N1515Q and N1574Q in both full-length VWF and A1-A2-A3. 27554083 10 12 located observed 1433:1440 arg1 VWF 1485:1487 full-length VWF 1473:1487 full-length VWF 1473:1487 Importantly, clodronate-induced macrophage depletion significantly attenuated the increased clearance observed with N1515Q and N1574Q in both full-length VWF and A1-A2-A3. 27554083 8 13 theme N-glycan 1045:1052 arg1 loss 1033:1036 loss 1033:1036 loss of the N-glycan at N1515 1033:1061 Indeed, loss of the N-glycan at N1515 resulted in markedly enhanced VWF clearance that was significantly faster than that observed with any previously described VWF mutations. 27554083 4 14 theme VWF 455:457 arg1 VWF 455:457 VWF 455:457 VWF 455:457 Our findings demonstrate that the A1 domain of VWF contains a receptor-recognition site that plays a key role in regulating the interaction of VWF with macrophages. 27554083 4 14 theme VWF 455:457 arg1 domain 445:450 the A1 domain 438:450 the A1 domain of VWF 438:457 Our findings demonstrate that the A1 domain of VWF contains a receptor-recognition site that plays a key role in regulating the interaction of VWF with macrophages. 27554083 12 15 theme VWF 1828:1830 arg1 clearance 1815:1823 macrophage-mediated clearance 1795:1823 macrophage-mediated clearance of VWF 1795:1830 Collectively, these novel findings support the hypothesis that conformation of the VWF A domains plays a critical role in modulating macrophage-mediated clearance of VWF in vivo. 27554083 4 16 with interaction 536:546 arg1 macrophages 560:570 macrophages 560:570 macrophages 560:570 Our findings demonstrate that the A1 domain of VWF contains a receptor-recognition site that plays a key role in regulating the interaction of VWF with macrophages. 27554083 4 17 contain contains 459:466 arg2 site 491:494 a receptor-recognition site 468:494 a receptor-recognition site that plays a key role in regulating the interaction of VWF with macrophages 468:570 Our findings demonstrate that the A1 domain of VWF contains a receptor-recognition site that plays a key role in regulating the interaction of VWF with macrophages. 27554083 4 17 contain contains 459:466 arg1 VWF 455:457 VWF 455:457 VWF 455:457 Our findings demonstrate that the A1 domain of VWF contains a receptor-recognition site that plays a key role in regulating the interaction of VWF with macrophages. 27554083 4 17 contain contains 459:466 arg1 domain 445:450 the A1 domain 438:450 the A1 domain of VWF 438:457 Our findings demonstrate that the A1 domain of VWF contains a receptor-recognition site that plays a key role in regulating the interaction of VWF with macrophages. 27554083 0 18 link N-linked 0:7 arg1 glycans 9:15 N-linked glycans 0:15 N-linked glycans within the A2 domain of von Willebrand factor 0:61 N-linked glycans within the A2 domain of von Willebrand factor modulate macrophage-mediated clearance. 27554083 3 19 theme VWF 334:336 arg1 domains 338:344 VWF domains 334:344 VWF domains 334:344 In this study, we investigated the role of VWF domains and specific glycan moieties in regulating in vivo clearance. 27554083 3 20 dep in 389:390 arg1 vivo 392:395 vivo 392:395 vivo 392:395 In this study, we investigated the role of VWF domains and specific glycan moieties in regulating in vivo clearance. 27554083 6 21 theme A2 781:782 arg1 domain 784:789 the A2 domain 777:789 the A2 domain 777:789 Previous studies have demonstrated that the N-linked glycans within the A2 domain play an important role in modulating susceptibility to ADAMTS13 proteolysis. 27554083 11 22 theme A2 1651:1652 arg1 domain 1654:1659 a structurally constrained A2 domain 1624:1659 a structurally constrained A2 domain 1624:1659 Finally, we further demonstrate that loss of these N-linked glycans does not enhance clearance in VWF in the presence of a structurally constrained A2 domain. 27554083 3 23 theme moieties 366:373 arg1 role 326:329 the role 322:329 the role of VWF domains and specific glycan moieties in regulating in vivo clearance 322:405 In this study, we investigated the role of VWF domains and specific glycan moieties in regulating in vivo clearance. 27554083 12 24 theme critical 1767:1774 arg1 role 1776:1779 a critical role 1765:1779 a critical role 1765:1779 Collectively, these novel findings support the hypothesis that conformation of the VWF A domains plays a critical role in modulating macrophage-mediated clearance of VWF in vivo. 27554083 0 25 theme N-linked 0:7 arg1 glycans 9:15 N-linked glycans 0:15 N-linked glycans within the A2 domain of von Willebrand factor 0:61 N-linked glycans within the A2 domain of von Willebrand factor modulate macrophage-mediated clearance. 27554083 5 26 theme macrophage-binding 611:628 arg1 site 630:633 this macrophage-binding site 606:633 this macrophage-binding site 606:633 In A1-A2-A3 and full-length VWF, this macrophage-binding site is cryptic but becomes exposed following exposure to shear or ristocetin. 27554083 3 27 theme specific 350:357 arg1 moieties 366:373 specific glycan moieties 350:373 specific glycan moieties 350:373 In this study, we investigated the role of VWF domains and specific glycan moieties in regulating in vivo clearance. 27554083 5 28 theme full-length 589:599 arg1 VWF 601:603 full-length VWF 589:603 full-length VWF 589:603 In A1-A2-A3 and full-length VWF, this macrophage-binding site is cryptic but becomes exposed following exposure to shear or ristocetin. 27554083 1 29 theme Enhanced 103:110 arg1 clearance 140:148 Enhanced von Willebrand factor (VWF) clearance 103:148 Enhanced von Willebrand factor (VWF) clearance 103:148 Enhanced von Willebrand factor (VWF) clearance is important in the etiology of von Willebrand disease. 27554083 7 30 theme critical 951:958 arg1 role 960:963 a critical role 949:963 a critical role 949:963 We further demonstrate that these glycans presented at N1515 and N1574 also play a critical role in protecting VWF against macrophage binding and clearance. 27554083 1 31 theme von 182:184 arg1 disease 197:203 von Willebrand disease 182:203 von Willebrand disease 182:203 Enhanced von Willebrand factor (VWF) clearance is important in the etiology of von Willebrand disease. 27554083 3 32 theme glycan 359:364 arg1 moieties 366:373 specific glycan moieties 350:373 specific glycan moieties 350:373 In this study, we investigated the role of VWF domains and specific glycan moieties in regulating in vivo clearance. 27554083 5 33 from VWF 601:603 arg1 cryptic 638:644 cryptic 638:644 cryptic 638:644 In A1-A2-A3 and full-length VWF, this macrophage-binding site is cryptic but becomes exposed following exposure to shear or ristocetin. 27554083 10 34 theme macrophage 1363:1372 arg1 depletion 1374:1382 clodronate-induced macrophage depletion 1344:1382 clodronate-induced macrophage depletion 1344:1382 Importantly, clodronate-induced macrophage depletion significantly attenuated the increased clearance observed with N1515Q and N1574Q in both full-length VWF and A1-A2-A3. 27554083 9 35 theme A1-A2-A3 1214:1221 arg1 fragments 1223:1231 A1-A2-A3 fragments 1214:1231 A1-A2-A3 fragments containing the N1515Q or N1574Q substitutions 1214:1277 In addition, A1-A2-A3 fragments containing the N1515Q or N1574Q substitutions also demonstrated significantly enhanced clearance. 27554083 1 36 theme von 112:114 arg1 VWF 135:137 VWF 135:137 VWF 135:137 Enhanced von Willebrand factor (VWF) clearance is important in the etiology of von Willebrand disease. 27554083 1 36 theme von 112:114 arg1 factor 127:132 von Willebrand factor 112:132 Enhanced von Willebrand factor (VWF) clearance 103:148 Enhanced von Willebrand factor (VWF) clearance is important in the etiology of von Willebrand disease. 27554083 1 37 theme Willebrand 186:195 arg1 disease 197:203 von Willebrand disease 182:203 von Willebrand disease 182:203 Enhanced von Willebrand factor (VWF) clearance is important in the etiology of von Willebrand disease. 27554083 11 38 link N-linked 1554:1561 arg1 glycans 1563:1569 these N-linked glycans 1548:1569 these N-linked glycans 1548:1569 Finally, we further demonstrate that loss of these N-linked glycans does not enhance clearance in VWF in the presence of a structurally constrained A2 domain. 27554083 2 39 theme molecular 219:227 arg1 mechanisms 229:238 the molecular mechanisms 215:238 the molecular mechanisms underlying VWF clearance 215:263 However, the molecular mechanisms underlying VWF clearance remain poorly understood. 27554083 12 40 theme novel 1682:1686 arg1 findings 1688:1695 these novel findings 1676:1695 these novel findings 1676:1695 Collectively, these novel findings support the hypothesis that conformation of the VWF A domains plays a critical role in modulating macrophage-mediated clearance of VWF in vivo. 27554083 1 41 theme disease 197:203 arg1 etiology 170:177 the etiology 166:177 the etiology of von Willebrand disease 166:203 Enhanced von Willebrand factor (VWF) clearance is important in the etiology of von Willebrand disease. 27554083 0 42 theme A2 28:29 arg1 domain 31:36 the A2 domain 24:36 the A2 domain of von Willebrand factor 24:61 N-linked glycans within the A2 domain of von Willebrand factor modulate macrophage-mediated clearance. 27554083 0 42 theme A2 28:29 arg1 factor 56:61 von Willebrand factor 41:61 von Willebrand factor 41:61 N-linked glycans within the A2 domain of von Willebrand factor modulate macrophage-mediated clearance. 27554083 4 43 theme key 509:511 arg1 role 513:516 a key role 507:516 a key role 507:516 Our findings demonstrate that the A1 domain of VWF contains a receptor-recognition site that plays a key role in regulating the interaction of VWF with macrophages. 27554083 6 44 theme ADAMTS13 846:853 arg1 proteolysis 855:865 ADAMTS13 proteolysis 846:865 ADAMTS13 proteolysis 846:865 Previous studies have demonstrated that the N-linked glycans within the A2 domain play an important role in modulating susceptibility to ADAMTS13 proteolysis. 27554083 6 45 link N-linked 753:760 arg1 glycans 762:768 the N-linked glycans 749:768 the N-linked glycans within the A2 domain 749:789 Previous studies have demonstrated that the N-linked glycans within the A2 domain play an important role in modulating susceptibility to ADAMTS13 proteolysis. 27554083 6 46 theme N-linked 753:760 arg1 glycans 762:768 the N-linked glycans 749:768 the N-linked glycans within the A2 domain 749:789 Previous studies have demonstrated that the N-linked glycans within the A2 domain play an important role in modulating susceptibility to ADAMTS13 proteolysis. 27554083 0 47 theme von 41:43 arg1 factor 56:61 von Willebrand factor 41:61 von Willebrand factor 41:61 N-linked glycans within the A2 domain of von Willebrand factor modulate macrophage-mediated clearance. 27554083 5 48 from cryptic 638:644 arg1 A1-A2-A3 576:583 A1-A2-A3 576:583 A1-A2-A3 576:583 In A1-A2-A3 and full-length VWF, this macrophage-binding site is cryptic but becomes exposed following exposure to shear or ristocetin. 27554083 5 48 from cryptic 638:644 arg1 VWF 601:603 full-length VWF 589:603 full-length VWF 589:603 In A1-A2-A3 and full-length VWF, this macrophage-binding site is cryptic but becomes exposed following exposure to shear or ristocetin. 27554083 8 49 theme VWF 1093:1095 arg1 clearance 1097:1105 markedly enhanced VWF clearance 1075:1105 markedly enhanced VWF clearance that was significantly faster than that observed with any previously described VWF mutations 1075:1198 Indeed, loss of the N-glycan at N1515 resulted in markedly enhanced VWF clearance that was significantly faster than that observed with any previously described VWF mutations. 27554083 4 50 theme A1 442:443 arg1 VWF 455:457 VWF 455:457 VWF 455:457 Our findings demonstrate that the A1 domain of VWF contains a receptor-recognition site that plays a key role in regulating the interaction of VWF with macrophages. 27554083 4 50 theme A1 442:443 arg1 domain 445:450 the A1 domain 438:450 the A1 domain of VWF 438:457 Our findings demonstrate that the A1 domain of VWF contains a receptor-recognition site that plays a key role in regulating the interaction of VWF with macrophages. 27554083 11 51 theme constrained 1639:1649 arg1 domain 1654:1659 a structurally constrained A2 domain 1624:1659 a structurally constrained A2 domain 1624:1659 Finally, we further demonstrate that loss of these N-linked glycans does not enhance clearance in VWF in the presence of a structurally constrained A2 domain. 27554083 1 52 theme Willebrand 116:125 arg1 VWF 135:137 VWF 135:137 VWF 135:137 Enhanced von Willebrand factor (VWF) clearance is important in the etiology of von Willebrand disease. 27554083 1 52 theme Willebrand 116:125 arg1 factor 127:132 von Willebrand factor 112:132 Enhanced von Willebrand factor (VWF) clearance 103:148 Enhanced von Willebrand factor (VWF) clearance is important in the etiology of von Willebrand disease. 27554083 3 53 theme in 389:390 arg1 clearance 397:405 in vivo clearance 389:405 in vivo clearance 389:405 In this study, we investigated the role of VWF domains and specific glycan moieties in regulating in vivo clearance. 27554083 8 54 theme enhanced 1084:1091 arg1 clearance 1097:1105 markedly enhanced VWF clearance 1075:1105 markedly enhanced VWF clearance that was significantly faster than that observed with any previously described VWF mutations 1075:1198 Indeed, loss of the N-glycan at N1515 resulted in markedly enhanced VWF clearance that was significantly faster than that observed with any previously described VWF mutations. 27554083 9 55 theme N1515Q 1248:1253 arg1 substitutions 1265:1277 the N1515Q or N1574Q substitutions 1244:1277 substitutions 1265:1277 In addition, A1-A2-A3 fragments containing the N1515Q or N1574Q substitutions also demonstrated significantly enhanced clearance. 27554083 7 56 theme macrophage 991:1000 arg1 binding 1002:1008 macrophage binding 991:1008 macrophage binding 991:1008 We further demonstrate that these glycans presented at N1515 and N1574 also play a critical role in protecting VWF against macrophage binding and clearance. 27554083 1 57 theme factor 127:132 arg1 clearance 140:148 Enhanced von Willebrand factor (VWF) clearance 103:148 Enhanced von Willebrand factor (VWF) clearance 103:148 Enhanced von Willebrand factor (VWF) clearance is important in the etiology of von Willebrand disease. 27554083 12 58 theme domains 1751:1757 arg1 conformation 1725:1736 conformation 1725:1736 conformation of the VWF A domains 1725:1757 Collectively, these novel findings support the hypothesis that conformation of the VWF A domains plays a critical role in modulating macrophage-mediated clearance of VWF in vivo. 27554083 10 59 theme full-length 1473:1483 arg1 VWF 1485:1487 full-length VWF 1473:1487 full-length VWF 1473:1487 Importantly, clodronate-induced macrophage depletion significantly attenuated the increased clearance observed with N1515Q and N1574Q in both full-length VWF and A1-A2-A3. 27554083 10 60 theme clodronate-induced 1344:1361 arg1 depletion 1374:1382 clodronate-induced macrophage depletion 1344:1382 clodronate-induced macrophage depletion 1344:1382 Importantly, clodronate-induced macrophage depletion significantly attenuated the increased clearance observed with N1515Q and N1574Q in both full-length VWF and A1-A2-A3. 27554083 9 61 contain containing 1233:1242 arg2 substitutions 1265:1277 the N1515Q or N1574Q substitutions 1244:1277 substitutions 1265:1277 In addition, A1-A2-A3 fragments containing the N1515Q or N1574Q substitutions also demonstrated significantly enhanced clearance. 27554083 9 61 contain containing 1233:1242 arg1 fragments 1223:1231 A1-A2-A3 fragments 1214:1231 A1-A2-A3 fragments containing the N1515Q or N1574Q substitutions 1214:1277 In addition, A1-A2-A3 fragments containing the N1515Q or N1574Q substitutions also demonstrated significantly enhanced clearance. 27554083 9 62 theme N1574Q 1258:1263 arg1 substitutions 1265:1277 the N1515Q or N1574Q substitutions 1244:1277 substitutions 1265:1277 In addition, A1-A2-A3 fragments containing the N1515Q or N1574Q substitutions also demonstrated significantly enhanced clearance. 27554083 2 63 theme VWF 251:253 arg1 clearance 255:263 VWF clearance 251:263 VWF clearance 251:263 However, the molecular mechanisms underlying VWF clearance remain poorly understood. 27554083 1 64 from etiology 170:177 arg1 important 153:161 important 153:161 important 153:161 Enhanced von Willebrand factor (VWF) clearance is important in the etiology of von Willebrand disease. 27554083 0 65 theme factor 56:61 arg1 domain 31:36 the A2 domain 24:36 the A2 domain of von Willebrand factor 24:61 N-linked glycans within the A2 domain of von Willebrand factor modulate macrophage-mediated clearance. 27554083 0 65 theme factor 56:61 arg1 factor 56:61 von Willebrand factor 41:61 von Willebrand factor 41:61 N-linked glycans within the A2 domain of von Willebrand factor modulate macrophage-mediated clearance. 27554083 12 66 theme macrophage-mediated 1795:1813 arg1 clearance 1815:1823 macrophage-mediated clearance 1795:1823 macrophage-mediated clearance of VWF 1795:1830 Collectively, these novel findings support the hypothesis that conformation of the VWF A domains plays a critical role in modulating macrophage-mediated clearance of VWF in vivo. 27554083 10 67 theme increased 1413:1421 arg1 clearance 1423:1431 the increased clearance 1409:1431 the increased clearance observed with N1515Q and N1574Q in both full-length VWF and A1-A2-A3 1409:1500 Importantly, clodronate-induced macrophage depletion significantly attenuated the increased clearance observed with N1515Q and N1574Q in both full-length VWF and A1-A2-A3. 27554083 12 68 theme A 1749:1749 arg1 domains 1751:1757 the VWF A domains 1741:1757 the VWF A domains 1741:1757 Collectively, these novel findings support the hypothesis that conformation of the VWF A domains plays a critical role in modulating macrophage-mediated clearance of VWF in vivo. 27554083 0 69 theme Willebrand 45:54 arg1 factor 56:61 von Willebrand factor 41:61 von Willebrand factor 41:61 N-linked glycans within the A2 domain of von Willebrand factor modulate macrophage-mediated clearance. 27554083 8 70 theme VWF 1186:1188 arg1 mutations 1190:1198 any previously described VWF mutations 1161:1198 any previously described VWF mutations 1161:1198 Indeed, loss of the N-glycan at N1515 resulted in markedly enhanced VWF clearance that was significantly faster than that observed with any previously described VWF mutations. 27554083 6 71 theme Previous 709:716 arg1 studies 718:724 Previous studies 709:724 Previous studies 709:724 Previous studies have demonstrated that the N-linked glycans within the A2 domain play an important role in modulating susceptibility to ADAMTS13 proteolysis. 27554083 8 72 theme described 1176:1184 arg1 mutations 1190:1198 any previously described VWF mutations 1161:1198 any previously described VWF mutations 1161:1198 Indeed, loss of the N-glycan at N1515 resulted in markedly enhanced VWF clearance that was significantly faster than that observed with any previously described VWF mutations. 27554083 11 73 theme glycans 1563:1569 arg1 loss 1540:1543 loss 1540:1543 loss of these N-linked glycans 1540:1569 Finally, we further demonstrate that loss of these N-linked glycans does not enhance clearance in VWF in the presence of a structurally constrained A2 domain. 27554083 8 74 from N1515 1057:1061 arg1 loss 1033:1036 loss 1033:1036 loss of the N-glycan at N1515 1033:1061 Indeed, loss of the N-glycan at N1515 resulted in markedly enhanced VWF clearance that was significantly faster than that observed with any previously described VWF mutations. 26324849 11 0 theme member 1847:1852 arg1 20C 1854:1856 sequence similarity member 20C 1827:1856 sequence similarity member 20C 1827:1856 Our results indicate that FAM20C is the primary, but not the only, kinase for the SIBLINGs.-Yang, X., Yan, W., Tian, Y., Ma, P., Opperman, L. A., Wang, X. Family with sequence similarity member 20C is the primary but not the only kinase for the small-integrin-binding ligand N-linked glycoproteins in bone. 26324849 11 1 theme sequence 1827:1834 arg1 20C 1854:1856 sequence similarity member 20C 1827:1856 sequence similarity member 20C 1827:1856 Our results indicate that FAM20C is the primary, but not the only, kinase for the SIBLINGs.-Yang, X., Yan, W., Tian, Y., Ma, P., Opperman, L. A., Wang, X. Family with sequence similarity member 20C is the primary but not the only kinase for the small-integrin-binding ligand N-linked glycoproteins in bone. 26324849 11 2 dep X. 1812:1813 arg1 X. 1758:1759 X. 1758:1759 X. 1758:1759 Our results indicate that FAM20C is the primary, but not the only, kinase for the SIBLINGs.-Yang, X., Yan, W., Tian, Y., Ma, P., Opperman, L. A., Wang, X. Family with sequence similarity member 20C is the primary but not the only kinase for the small-integrin-binding ligand N-linked glycoproteins in bone. 26324849 9 3 theme several 1521:1527 arg1 others 1529:1534 several others 1521:1534 several others in non-Ser-X-Glu motifs 1521:1558 In an intriguing finding, several pSers in the Ser-X-Glu motifs in the KO mice maintained their phosphorylation, whereas several others in non-Ser-X-Glu motifs did not. 26324849 6 4 from mice 980:983 arg1 SIBLINGs 963:970 the SIBLINGs 959:970 the SIBLINGs from KO mice 959:983 On the native gel, the SIBLINGs from KO mice showed a lower migration rate (Mr) than those from the WT. 26324849 9 5 from others 1529:1534 arg1 motifs 1553:1558 non-Ser-X-Glu motifs 1539:1558 non-Ser-X-Glu motifs 1539:1558 In an intriguing finding, several pSers in the Ser-X-Glu motifs in the KO mice maintained their phosphorylation, whereas several others in non-Ser-X-Glu motifs did not. 26324849 10 6 from Phospho-Tyrs 1569:1580 arg1 SIBLINGs 1606:1613 the SIBLINGs 1602:1613 the SIBLINGs 1602:1613 Phospho-Tyrs and phospho-Thrs in the SIBLINGs did not appear to be associated with FAM20C. 26324849 0 7 theme small-integrin-binding 90:111 arg1 glycoproteins 129:141 the small-integrin-binding ligand N-linked glycoproteins 86:141 the small-integrin-binding ligand N-linked glycoproteins in bone 86:149 Family with sequence similarity member 20C is the primary but not the only kinase for the small-integrin-binding ligand N-linked glycoproteins in bone. 26324849 3 8 theme bone 523:526 arg1 NCPs 553:556 NCPs 553:556 NCPs 553:556 We extracted bone noncollagenous proteins (NCPs) from Fam20C-knockout (KO) mice and analyzed the phosphorylation levels. 26324849 3 8 theme bone 523:526 arg1 proteins 543:550 bone noncollagenous proteins 523:550 bone noncollagenous proteins (NCPs) 523:557 We extracted bone noncollagenous proteins (NCPs) from Fam20C-knockout (KO) mice and analyzed the phosphorylation levels. 26324849 1 9 theme sequence 195:202 arg1 similarity 204:213 sequence similarity member 20C (FAM20C) 195:233 sequence similarity member 20C (FAM20C) 195:233 Recent studies have identified family with sequence similarity member 20C (FAM20C) as a kinase that phosphorylates the Ser in Ser-X-Glu/phospho-Ser (pSer) motifs in the small-integrin-binding ligand N-linked glycoproteins (SIBLINGs). 26324849 8 10 theme KO 1307:1308 arg1 mice 1310:1313 the KO mice 1303:1313 the KO mice [including the region of the acidic Ser- and aspartate-rich motif (ASARM) peptides 1303:1396 Mass spectrometry identified less pSers in the SIBLINGs from the KO mice [including the region of the acidic Ser- and aspartate-rich motif (ASARM) peptides]. 26324849 0 11 theme N-linked 120:127 arg1 glycoproteins 129:141 the small-integrin-binding ligand N-linked glycoproteins 86:141 the small-integrin-binding ligand N-linked glycoproteins in bone 86:149 Family with sequence similarity member 20C is the primary but not the only kinase for the small-integrin-binding ligand N-linked glycoproteins in bone. 26324849 7 12 theme phosphatase 1059:1069 arg1 treatment 1071:1079 Calf intestine phosphatase treatment 1044:1079 Calf intestine phosphatase treatment 1044:1079 Calf intestine phosphatase treatment shifted SIBLINGs from the WT mice to the level adjacent to the KO, but failed to shift the latter, suggesting a phosphorylation loss of SIBLINGs in the KO mice. 26324849 1 13 theme member 215:220 arg1 FAM20C 227:232 FAM20C 227:232 FAM20C 227:232 Recent studies have identified family with sequence similarity member 20C (FAM20C) as a kinase that phosphorylates the Ser in Ser-X-Glu/phospho-Ser (pSer) motifs in the small-integrin-binding ligand N-linked glycoproteins (SIBLINGs). 26324849 1 13 theme member 215:220 arg1 20C 222:224 member 20C 215:224 sequence similarity member 20C (FAM20C) 195:233 Recent studies have identified family with sequence similarity member 20C (FAM20C) as a kinase that phosphorylates the Ser in Ser-X-Glu/phospho-Ser (pSer) motifs in the small-integrin-binding ligand N-linked glycoproteins (SIBLINGs). 26324849 7 14 from mice 1110:1113 arg1 SIBLINGs 1089:1096 SIBLINGs 1089:1096 SIBLINGs from the WT mice 1089:1113 Calf intestine phosphatase treatment shifted SIBLINGs from the WT mice to the level adjacent to the KO, but failed to shift the latter, suggesting a phosphorylation loss of SIBLINGs in the KO mice. 26324849 5 15 theme KO 889:890 arg1 mice 892:895 the KO mice 885:895 the KO mice 885:895 The NCP phosphorylation level in the KO mice was lower than that in the wild-type (WT). 26324849 4 16 theme bone 680:683 arg1 sialoprotein- 685:697 bone sialoprotein- 680:697 bone sialoprotein- 680:697 The total NCPs were separated into osteopontin-, bone sialoprotein-, and dentin matrix protein-1-enriched fractions by anion-exchange chromatography and analyzed by SDS-PAGE, native PAGE, and Western immunoblot analysis. 26324849 0 17 gly glycoproteins 129:141 arg1 glycoproteins 129:141 the small-integrin-binding ligand N-linked glycoproteins 86:141 the small-integrin-binding ligand N-linked glycoproteins in bone 86:149 Family with sequence similarity member 20C is the primary but not the only kinase for the small-integrin-binding ligand N-linked glycoproteins in bone. 26324849 7 18 theme SIBLINGs 1217:1224 arg1 loss 1209:1212 a phosphorylation loss 1191:1212 a phosphorylation loss of SIBLINGs in the KO mice 1191:1239 Calf intestine phosphatase treatment shifted SIBLINGs from the WT mice to the level adjacent to the KO, but failed to shift the latter, suggesting a phosphorylation loss of SIBLINGs in the KO mice. 26324849 7 19 theme adjacent 1128:1135 arg1 level 1122:1126 the level 1118:1126 the level adjacent to the KO 1118:1145 Calf intestine phosphatase treatment shifted SIBLINGs from the WT mice to the level adjacent to the KO, but failed to shift the latter, suggesting a phosphorylation loss of SIBLINGs in the KO mice. 26324849 5 20 theme phosphorylation 860:874 arg1 level 876:880 The NCP phosphorylation level 852:880 The NCP phosphorylation level in the KO mice 852:895 The NCP phosphorylation level in the KO mice was lower than that in the wild-type (WT). 26324849 5 20 theme phosphorylation 860:874 arg1 lower 901:905 lower 901:905 lower 901:905 The NCP phosphorylation level in the KO mice was lower than that in the wild-type (WT). 26324849 6 21 theme native 947:952 arg1 gel 954:956 the native gel 943:956 the native gel 943:956 On the native gel, the SIBLINGs from KO mice showed a lower migration rate (Mr) than those from the WT. 26324849 11 22 theme N-linked 1935:1942 arg1 glycoproteins 1944:1956 the small-integrin-binding ligand N-linked glycoproteins 1901:1956 the small-integrin-binding ligand N-linked glycoproteins in bone 1901:1964 Our results indicate that FAM20C is the primary, but not the only, kinase for the SIBLINGs.-Yang, X., Yan, W., Tian, Y., Ma, P., Opperman, L. A., Wang, X. Family with sequence similarity member 20C is the primary but not the only kinase for the small-integrin-binding ligand N-linked glycoproteins in bone. 26324849 8 23 theme Ser- 1351:1354 arg1 peptides 1389:1396 the acidic Ser- and aspartate-rich motif (ASARM) peptides 1340:1396 the acidic Ser- and aspartate-rich motif (ASARM) peptides 1340:1396 Mass spectrometry identified less pSers in the SIBLINGs from the KO mice [including the region of the acidic Ser- and aspartate-rich motif (ASARM) peptides]. 26324849 5 24 from level 876:880 arg1 mice 892:895 the KO mice 885:895 the KO mice 885:895 The NCP phosphorylation level in the KO mice was lower than that in the wild-type (WT). 26324849 1 25 theme Recent 152:157 arg1 studies 159:165 Recent studies 152:165 Recent studies 152:165 Recent studies have identified family with sequence similarity member 20C (FAM20C) as a kinase that phosphorylates the Ser in Ser-X-Glu/phospho-Ser (pSer) motifs in the small-integrin-binding ligand N-linked glycoproteins (SIBLINGs). 26324849 8 26 theme aspartate-rich 1360:1373 arg1 ASARM 1382:1386 ASARM 1382:1386 ASARM 1382:1386 Mass spectrometry identified less pSers in the SIBLINGs from the KO mice [including the region of the acidic Ser- and aspartate-rich motif (ASARM) peptides]. 26324849 8 26 theme aspartate-rich 1360:1373 arg1 motif 1375:1379 aspartate-rich motif 1360:1379 aspartate-rich motif (ASARM) 1360:1387 Mass spectrometry identified less pSers in the SIBLINGs from the KO mice [including the region of the acidic Ser- and aspartate-rich motif (ASARM) peptides]. 26324849 4 27 theme protein-1-enriched 718:735 arg1 fractions 737:745 dentin matrix protein-1-enriched fractions 704:745 dentin matrix protein-1-enriched fractions 704:745 The total NCPs were separated into osteopontin-, bone sialoprotein-, and dentin matrix protein-1-enriched fractions by anion-exchange chromatography and analyzed by SDS-PAGE, native PAGE, and Western immunoblot analysis. 26324849 0 28 theme only 70:73 arg1 kinase 75:80 the primary but not the only kinase 46:80 the primary but not the only kinase for the small-integrin-binding ligand N-linked glycoproteins in bone 46:149 Family with sequence similarity member 20C is the primary but not the only kinase for the small-integrin-binding ligand N-linked glycoproteins in bone. 26324849 0 28 theme only 70:73 arg1 Family 0:5 Family 0:5 Family with sequence similarity member 20C 0:41 Family with sequence similarity member 20C is the primary but not the only kinase for the small-integrin-binding ligand N-linked glycoproteins in bone. 26324849 1 29 theme ligand 344:349 arg1 SIBLINGs 375:382 SIBLINGs 375:382 SIBLINGs 375:382 Recent studies have identified family with sequence similarity member 20C (FAM20C) as a kinase that phosphorylates the Ser in Ser-X-Glu/phospho-Ser (pSer) motifs in the small-integrin-binding ligand N-linked glycoproteins (SIBLINGs). 26324849 1 29 theme ligand 344:349 arg1 glycoproteins 360:372 the small-integrin-binding ligand N-linked glycoproteins 317:372 the small-integrin-binding ligand N-linked glycoproteins (SIBLINGs) 317:383 Recent studies have identified family with sequence similarity member 20C (FAM20C) as a kinase that phosphorylates the Ser in Ser-X-Glu/phospho-Ser (pSer) motifs in the small-integrin-binding ligand N-linked glycoproteins (SIBLINGs). 26324849 9 30 from motifs 1457:1462 arg1 mice 1474:1477 the KO mice 1467:1477 the KO mice 1467:1477 In an intriguing finding, several pSers in the Ser-X-Glu motifs in the KO mice maintained their phosphorylation, whereas several others in non-Ser-X-Glu motifs did not. 26324849 6 31 theme lower 994:998 arg1 Mr 1016:1017 Mr 1016:1017 Mr 1016:1017 On the native gel, the SIBLINGs from KO mice showed a lower migration rate (Mr) than those from the WT. 26324849 6 31 theme lower 994:998 arg1 rate 1010:1013 a lower migration rate 992:1013 a lower migration rate (Mr) 992:1018 On the native gel, the SIBLINGs from KO mice showed a lower migration rate (Mr) than those from the WT. 26324849 11 32 theme only 1885:1888 arg1 kinase 1890:1895 the only kinase 1881:1895 but not the only, kinase for the SIBLINGs.-Yang, X., Yan, W., Tian, Y., Ma, P., Opperman, L. A., Wang, X. Family with sequence similarity member 20C is the primary but not the only kinase 1709:1895 Our results indicate that FAM20C is the primary, but not the only, kinase for the SIBLINGs.-Yang, X., Yan, W., Tian, Y., Ma, P., Opperman, L. A., Wang, X. Family with sequence similarity member 20C is the primary but not the only kinase for the small-integrin-binding ligand N-linked glycoproteins in bone. 26324849 1 33 link N-linked 351:358 arg1 SIBLINGs 375:382 SIBLINGs 375:382 SIBLINGs 375:382 Recent studies have identified family with sequence similarity member 20C (FAM20C) as a kinase that phosphorylates the Ser in Ser-X-Glu/phospho-Ser (pSer) motifs in the small-integrin-binding ligand N-linked glycoproteins (SIBLINGs). 26324849 1 33 link N-linked 351:358 arg1 glycoproteins 360:372 the small-integrin-binding ligand N-linked glycoproteins 317:372 the small-integrin-binding ligand N-linked glycoproteins (SIBLINGs) 317:383 Recent studies have identified family with sequence similarity member 20C (FAM20C) as a kinase that phosphorylates the Ser in Ser-X-Glu/phospho-Ser (pSer) motifs in the small-integrin-binding ligand N-linked glycoproteins (SIBLINGs). 26324849 7 34 theme phosphorylation 1193:1207 arg1 loss 1209:1212 a phosphorylation loss 1191:1212 a phosphorylation loss of SIBLINGs in the KO mice 1191:1239 Calf intestine phosphatase treatment shifted SIBLINGs from the WT mice to the level adjacent to the KO, but failed to shift the latter, suggesting a phosphorylation loss of SIBLINGs in the KO mice. 26324849 4 35 theme dentin 704:709 arg1 fractions 737:745 dentin matrix protein-1-enriched fractions 704:745 dentin matrix protein-1-enriched fractions 704:745 The total NCPs were separated into osteopontin-, bone sialoprotein-, and dentin matrix protein-1-enriched fractions by anion-exchange chromatography and analyzed by SDS-PAGE, native PAGE, and Western immunoblot analysis. 26324849 0 36 theme sequence 12:19 arg1 similarity 21:30 sequence similarity 12:30 sequence similarity member 20C 12:41 Family with sequence similarity member 20C is the primary but not the only kinase for the small-integrin-binding ligand N-linked glycoproteins in bone. 26324849 9 37 theme several 1426:1432 arg1 pSers 1434:1438 several pSers 1426:1438 several pSers in the Ser-X-Glu motifs in the KO mice 1426:1477 In an intriguing finding, several pSers in the Ser-X-Glu motifs in the KO mice maintained their phosphorylation, whereas several others in non-Ser-X-Glu motifs did not. 26324849 9 38 from pSers 1434:1438 arg1 motifs 1457:1462 the Ser-X-Glu motifs 1443:1462 the Ser-X-Glu motifs in the KO mice 1443:1477 In an intriguing finding, several pSers in the Ser-X-Glu motifs in the KO mice maintained their phosphorylation, whereas several others in non-Ser-X-Glu motifs did not. 26324849 6 39 theme KO 977:978 arg1 mice 980:983 KO mice 977:983 KO mice 977:983 On the native gel, the SIBLINGs from KO mice showed a lower migration rate (Mr) than those from the WT. 26324849 11 40 theme small-integrin-binding 1905:1926 arg1 glycoproteins 1944:1956 the small-integrin-binding ligand N-linked glycoproteins 1901:1956 the small-integrin-binding ligand N-linked glycoproteins in bone 1901:1964 Our results indicate that FAM20C is the primary, but not the only, kinase for the SIBLINGs.-Yang, X., Yan, W., Tian, Y., Ma, P., Opperman, L. A., Wang, X. Family with sequence similarity member 20C is the primary but not the only kinase for the small-integrin-binding ligand N-linked glycoproteins in bone. 26324849 8 41 theme less 1271:1274 arg1 pSers 1276:1280 less pSers 1271:1280 less pSers 1271:1280 Mass spectrometry identified less pSers in the SIBLINGs from the KO mice [including the region of the acidic Ser- and aspartate-rich motif (ASARM) peptides]. 26324849 7 42 theme intestine 1049:1057 arg1 treatment 1071:1079 Calf intestine phosphatase treatment 1044:1079 Calf intestine phosphatase treatment 1044:1079 Calf intestine phosphatase treatment shifted SIBLINGs from the WT mice to the level adjacent to the KO, but failed to shift the latter, suggesting a phosphorylation loss of SIBLINGs in the KO mice. 26324849 1 43 theme Ser-X-Glu/phospho-Ser 278:298 arg1 motifs 307:312 Ser-X-Glu/phospho-Ser (pSer) motifs 278:312 Ser-X-Glu/phospho-Ser (pSer) motifs in the small-integrin-binding ligand N-linked glycoproteins (SIBLINGs) 278:383 Recent studies have identified family with sequence similarity member 20C (FAM20C) as a kinase that phosphorylates the Ser in Ser-X-Glu/phospho-Ser (pSer) motifs in the small-integrin-binding ligand N-linked glycoproteins (SIBLINGs). 26324849 0 44 theme member 32:37 arg1 20C 39:41 sequence similarity member 20C 12:41 sequence similarity member 20C 12:41 Family with sequence similarity member 20C is the primary but not the only kinase for the small-integrin-binding ligand N-linked glycoproteins in bone. 26324849 0 45 theme primary 50:56 arg1 kinase 75:80 the primary but not the only kinase 46:80 the primary but not the only kinase for the small-integrin-binding ligand N-linked glycoproteins in bone 46:149 Family with sequence similarity member 20C is the primary but not the only kinase for the small-integrin-binding ligand N-linked glycoproteins in bone. 26324849 0 45 theme primary 50:56 arg1 Family 0:5 Family 0:5 Family with sequence similarity member 20C 0:41 Family with sequence similarity member 20C is the primary but not the only kinase for the small-integrin-binding ligand N-linked glycoproteins in bone. 26324849 4 46 theme native 806:811 arg1 PAGE 813:816 native PAGE 806:816 native PAGE 806:816 The total NCPs were separated into osteopontin-, bone sialoprotein-, and dentin matrix protein-1-enriched fractions by anion-exchange chromatography and analyzed by SDS-PAGE, native PAGE, and Western immunoblot analysis. 26324849 1 47 theme pSer 301:304 arg1 motifs 307:312 Ser-X-Glu/phospho-Ser (pSer) motifs 278:312 Ser-X-Glu/phospho-Ser (pSer) motifs in the small-integrin-binding ligand N-linked glycoproteins (SIBLINGs) 278:383 Recent studies have identified family with sequence similarity member 20C (FAM20C) as a kinase that phosphorylates the Ser in Ser-X-Glu/phospho-Ser (pSer) motifs in the small-integrin-binding ligand N-linked glycoproteins (SIBLINGs). 26324849 1 48 with family 183:188 arg1 similarity 204:213 sequence similarity member 20C (FAM20C) 195:233 sequence similarity member 20C (FAM20C) 195:233 Recent studies have identified family with sequence similarity member 20C (FAM20C) as a kinase that phosphorylates the Ser in Ser-X-Glu/phospho-Ser (pSer) motifs in the small-integrin-binding ligand N-linked glycoproteins (SIBLINGs). 26324849 9 49 theme Ser-X-Glu 1447:1455 arg1 motifs 1457:1462 the Ser-X-Glu motifs 1443:1462 the Ser-X-Glu motifs in the KO mice 1443:1477 In an intriguing finding, several pSers in the Ser-X-Glu motifs in the KO mice maintained their phosphorylation, whereas several others in non-Ser-X-Glu motifs did not. 26324849 11 50 from glycoproteins 1944:1956 arg1 bone 1961:1964 bone 1961:1964 bone 1961:1964 Our results indicate that FAM20C is the primary, but not the only, kinase for the SIBLINGs.-Yang, X., Yan, W., Tian, Y., Ma, P., Opperman, L. A., Wang, X. Family with sequence similarity member 20C is the primary but not the only kinase for the small-integrin-binding ligand N-linked glycoproteins in bone. 26324849 1 51 dep similarity 204:213 arg1 FAM20C 227:232 FAM20C 227:232 FAM20C 227:232 Recent studies have identified family with sequence similarity member 20C (FAM20C) as a kinase that phosphorylates the Ser in Ser-X-Glu/phospho-Ser (pSer) motifs in the small-integrin-binding ligand N-linked glycoproteins (SIBLINGs). 26324849 1 51 dep similarity 204:213 arg1 20C 222:224 member 20C 215:224 sequence similarity member 20C (FAM20C) 195:233 Recent studies have identified family with sequence similarity member 20C (FAM20C) as a kinase that phosphorylates the Ser in Ser-X-Glu/phospho-Ser (pSer) motifs in the small-integrin-binding ligand N-linked glycoproteins (SIBLINGs). 26324849 0 52 with Family 0:5 arg1 20C 39:41 sequence similarity member 20C 12:41 sequence similarity member 20C 12:41 Family with sequence similarity member 20C is the primary but not the only kinase for the small-integrin-binding ligand N-linked glycoproteins in bone. 26324849 9 53 theme KO 1471:1472 arg1 mice 1474:1477 the KO mice 1467:1477 the KO mice 1467:1477 In an intriguing finding, several pSers in the Ser-X-Glu motifs in the KO mice maintained their phosphorylation, whereas several others in non-Ser-X-Glu motifs did not. 26324849 7 54 from loss 1209:1212 arg1 mice 1236:1239 the KO mice 1229:1239 the KO mice 1229:1239 Calf intestine phosphatase treatment shifted SIBLINGs from the WT mice to the level adjacent to the KO, but failed to shift the latter, suggesting a phosphorylation loss of SIBLINGs in the KO mice. 26324849 11 55 theme primary 1700:1706 arg1 kinase 1727:1732 kinase 1727:1732 kinase for the SIBLINGs.-Yang, X., Yan, W., Tian, Y., Ma, P., Opperman, L. A., Wang, X. Family with sequence similarity member 20C 1727:1856 Our results indicate that FAM20C is the primary, but not the only, kinase for the SIBLINGs.-Yang, X., Yan, W., Tian, Y., Ma, P., Opperman, L. A., Wang, X. Family with sequence similarity member 20C is the primary but not the only kinase for the small-integrin-binding ligand N-linked glycoproteins in bone. 26324849 11 55 theme primary 1700:1706 arg1 FAM20C 1686:1691 FAM20C 1686:1691 FAM20C 1686:1691 Our results indicate that FAM20C is the primary, but not the only, kinase for the SIBLINGs.-Yang, X., Yan, W., Tian, Y., Ma, P., Opperman, L. A., Wang, X. Family with sequence similarity member 20C is the primary but not the only kinase for the small-integrin-binding ligand N-linked glycoproteins in bone. 26324849 4 56 theme immunoblot 831:840 arg1 analysis 842:849 Western immunoblot analysis 823:849 Western immunoblot analysis 823:849 The total NCPs were separated into osteopontin-, bone sialoprotein-, and dentin matrix protein-1-enriched fractions by anion-exchange chromatography and analyzed by SDS-PAGE, native PAGE, and Western immunoblot analysis. 26324849 11 57 link N-linked 1935:1942 arg1 glycoproteins 1944:1956 the small-integrin-binding ligand N-linked glycoproteins 1901:1956 the small-integrin-binding ligand N-linked glycoproteins in bone 1901:1964 Our results indicate that FAM20C is the primary, but not the only, kinase for the SIBLINGs.-Yang, X., Yan, W., Tian, Y., Ma, P., Opperman, L. A., Wang, X. Family with sequence similarity member 20C is the primary but not the only kinase for the small-integrin-binding ligand N-linked glycoproteins in bone. 26324849 11 58 theme similarity 1836:1845 arg1 20C 1854:1856 sequence similarity member 20C 1827:1856 sequence similarity member 20C 1827:1856 Our results indicate that FAM20C is the primary, but not the only, kinase for the SIBLINGs.-Yang, X., Yan, W., Tian, Y., Ma, P., Opperman, L. A., Wang, X. Family with sequence similarity member 20C is the primary but not the only kinase for the small-integrin-binding ligand N-linked glycoproteins in bone. 26324849 1 59 from Ser 271:273 arg1 motifs 307:312 Ser-X-Glu/phospho-Ser (pSer) motifs 278:312 Ser-X-Glu/phospho-Ser (pSer) motifs in the small-integrin-binding ligand N-linked glycoproteins (SIBLINGs) 278:383 Recent studies have identified family with sequence similarity member 20C (FAM20C) as a kinase that phosphorylates the Ser in Ser-X-Glu/phospho-Ser (pSer) motifs in the small-integrin-binding ligand N-linked glycoproteins (SIBLINGs). 26324849 3 60 theme noncollagenous 528:541 arg1 NCPs 553:556 NCPs 553:556 NCPs 553:556 We extracted bone noncollagenous proteins (NCPs) from Fam20C-knockout (KO) mice and analyzed the phosphorylation levels. 26324849 3 60 theme noncollagenous 528:541 arg1 proteins 543:550 bone noncollagenous proteins 523:550 bone noncollagenous proteins (NCPs) 523:557 We extracted bone noncollagenous proteins (NCPs) from Fam20C-knockout (KO) mice and analyzed the phosphorylation levels. 26324849 11 61 gly glycoproteins 1944:1956 arg1 glycoproteins 1944:1956 the small-integrin-binding ligand N-linked glycoproteins 1901:1956 the small-integrin-binding ligand N-linked glycoproteins in bone 1901:1964 Our results indicate that FAM20C is the primary, but not the only, kinase for the SIBLINGs.-Yang, X., Yan, W., Tian, Y., Ma, P., Opperman, L. A., Wang, X. Family with sequence similarity member 20C is the primary but not the only kinase for the small-integrin-binding ligand N-linked glycoproteins in bone. 26324849 0 62 theme ligand 113:118 arg1 glycoproteins 129:141 the small-integrin-binding ligand N-linked glycoproteins 86:141 the small-integrin-binding ligand N-linked glycoproteins in bone 86:149 Family with sequence similarity member 20C is the primary but not the only kinase for the small-integrin-binding ligand N-linked glycoproteins in bone. 26324849 11 63 dep kinase 1727:1732 arg1 primary 1865:1871 primary 1865:1871 primary 1865:1871 Our results indicate that FAM20C is the primary, but not the only, kinase for the SIBLINGs.-Yang, X., Yan, W., Tian, Y., Ma, P., Opperman, L. A., Wang, X. Family with sequence similarity member 20C is the primary but not the only kinase for the small-integrin-binding ligand N-linked glycoproteins in bone. 26324849 4 64 theme Western 823:829 arg1 analysis 842:849 Western immunoblot analysis 823:849 Western immunoblot analysis 823:849 The total NCPs were separated into osteopontin-, bone sialoprotein-, and dentin matrix protein-1-enriched fractions by anion-exchange chromatography and analyzed by SDS-PAGE, native PAGE, and Western immunoblot analysis. 26324849 9 65 theme non-Ser-X-Glu 1539:1551 arg1 motifs 1553:1558 non-Ser-X-Glu motifs 1539:1558 non-Ser-X-Glu motifs 1539:1558 In an intriguing finding, several pSers in the Ser-X-Glu motifs in the KO mice maintained their phosphorylation, whereas several others in non-Ser-X-Glu motifs did not. 26324849 1 66 gly glycoproteins 360:372 arg1 SIBLINGs 375:382 SIBLINGs 375:382 SIBLINGs 375:382 Recent studies have identified family with sequence similarity member 20C (FAM20C) as a kinase that phosphorylates the Ser in Ser-X-Glu/phospho-Ser (pSer) motifs in the small-integrin-binding ligand N-linked glycoproteins (SIBLINGs). 26324849 1 66 gly glycoproteins 360:372 arg1 glycoproteins 360:372 the small-integrin-binding ligand N-linked glycoproteins 317:372 the small-integrin-binding ligand N-linked glycoproteins (SIBLINGs) 317:383 Recent studies have identified family with sequence similarity member 20C (FAM20C) as a kinase that phosphorylates the Ser in Ser-X-Glu/phospho-Ser (pSer) motifs in the small-integrin-binding ligand N-linked glycoproteins (SIBLINGs). 26324849 3 67 theme KO 581:582 arg1 mice 585:588 Fam20C-knockout (KO) mice 564:588 Fam20C-knockout (KO) mice 564:588 We extracted bone noncollagenous proteins (NCPs) from Fam20C-knockout (KO) mice and analyzed the phosphorylation levels. 26324849 10 68 from phospho-Thrs 1586:1597 arg1 SIBLINGs 1606:1613 the SIBLINGs 1602:1613 the SIBLINGs 1602:1613 Phospho-Tyrs and phospho-Thrs in the SIBLINGs did not appear to be associated with FAM20C. 26324849 11 69 theme X. 1812:1813 arg1 Family 1815:1820 the SIBLINGs.-Yang, X., Yan, W., Tian, Y., Ma, P., Opperman, L. A., Wang, X. Family 1738:1820 the SIBLINGs.-Yang, X., Yan, W., Tian, Y., Ma, P., Opperman, L. A., Wang, X. Family with sequence similarity member 20C 1738:1856 Our results indicate that FAM20C is the primary, but not the only, kinase for the SIBLINGs.-Yang, X., Yan, W., Tian, Y., Ma, P., Opperman, L. A., Wang, X. Family with sequence similarity member 20C is the primary but not the only kinase for the small-integrin-binding ligand N-linked glycoproteins in bone. 26324849 8 70 theme acidic 1344:1349 arg1 peptides 1389:1396 the acidic Ser- and aspartate-rich motif (ASARM) peptides 1340:1396 the acidic Ser- and aspartate-rich motif (ASARM) peptides 1340:1396 Mass spectrometry identified less pSers in the SIBLINGs from the KO mice [including the region of the acidic Ser- and aspartate-rich motif (ASARM) peptides]. 26324849 7 71 theme KO 1233:1234 arg1 mice 1236:1239 the KO mice 1229:1239 the KO mice 1229:1239 Calf intestine phosphatase treatment shifted SIBLINGs from the WT mice to the level adjacent to the KO, but failed to shift the latter, suggesting a phosphorylation loss of SIBLINGs in the KO mice. 26324849 5 72 dep wild-type 924:932 arg1 WT 935:936 WT 935:936 WT 935:936 The NCP phosphorylation level in the KO mice was lower than that in the wild-type (WT). 26324849 3 73 theme Fam20C-knockout 564:578 arg1 mice 585:588 Fam20C-knockout (KO) mice 564:588 Fam20C-knockout (KO) mice 564:588 We extracted bone noncollagenous proteins (NCPs) from Fam20C-knockout (KO) mice and analyzed the phosphorylation levels. 26324849 5 74 theme NCP 856:858 arg1 level 876:880 The NCP phosphorylation level 852:880 The NCP phosphorylation level in the KO mice 852:895 The NCP phosphorylation level in the KO mice was lower than that in the wild-type (WT). 26324849 5 74 theme NCP 856:858 arg1 lower 901:905 lower 901:905 lower 901:905 The NCP phosphorylation level in the KO mice was lower than that in the wild-type (WT). 26324849 4 75 theme total 635:639 arg1 NCPs 641:644 The total NCPs 631:644 The total NCPs 631:644 The total NCPs were separated into osteopontin-, bone sialoprotein-, and dentin matrix protein-1-enriched fractions by anion-exchange chromatography and analyzed by SDS-PAGE, native PAGE, and Western immunoblot analysis. 26324849 8 76 from mice 1310:1313 arg1 SIBLINGs 1289:1296 the SIBLINGs 1285:1296 the SIBLINGs from the KO mice [including the region of the acidic Ser- and aspartate-rich motif (ASARM) peptides 1285:1396 Mass spectrometry identified less pSers in the SIBLINGs from the KO mice [including the region of the acidic Ser- and aspartate-rich motif (ASARM) peptides]. 26324849 8 77 theme motif 1375:1379 arg1 peptides 1389:1396 the acidic Ser- and aspartate-rich motif (ASARM) peptides 1340:1396 the acidic Ser- and aspartate-rich motif (ASARM) peptides 1340:1396 Mass spectrometry identified less pSers in the SIBLINGs from the KO mice [including the region of the acidic Ser- and aspartate-rich motif (ASARM) peptides]. 26324849 7 78 theme WT 1107:1108 arg1 mice 1110:1113 the WT mice 1103:1113 the WT mice 1103:1113 Calf intestine phosphatase treatment shifted SIBLINGs from the WT mice to the level adjacent to the KO, but failed to shift the latter, suggesting a phosphorylation loss of SIBLINGs in the KO mice. 26324849 1 79 theme small-integrin-binding 321:342 arg1 SIBLINGs 375:382 SIBLINGs 375:382 SIBLINGs 375:382 Recent studies have identified family with sequence similarity member 20C (FAM20C) as a kinase that phosphorylates the Ser in Ser-X-Glu/phospho-Ser (pSer) motifs in the small-integrin-binding ligand N-linked glycoproteins (SIBLINGs). 26324849 1 79 theme small-integrin-binding 321:342 arg1 glycoproteins 360:372 the small-integrin-binding ligand N-linked glycoproteins 317:372 the small-integrin-binding ligand N-linked glycoproteins (SIBLINGs) 317:383 Recent studies have identified family with sequence similarity member 20C (FAM20C) as a kinase that phosphorylates the Ser in Ser-X-Glu/phospho-Ser (pSer) motifs in the small-integrin-binding ligand N-linked glycoproteins (SIBLINGs). 26324849 2 80 theme only 484:487 arg1 FAM20C 470:475 FAM20C 470:475 FAM20C 470:475 There is no in vivo evidence that validates this finding, and it is unclear whether FAM20C is the only kinase for SIBLINGs. 26324849 2 80 theme only 484:487 arg1 kinase 489:494 the only kinase 480:494 the only kinase for SIBLINGs 480:507 There is no in vivo evidence that validates this finding, and it is unclear whether FAM20C is the only kinase for SIBLINGs. 26324849 4 81 theme matrix 711:716 arg1 fractions 737:745 dentin matrix protein-1-enriched fractions 704:745 dentin matrix protein-1-enriched fractions 704:745 The total NCPs were separated into osteopontin-, bone sialoprotein-, and dentin matrix protein-1-enriched fractions by anion-exchange chromatography and analyzed by SDS-PAGE, native PAGE, and Western immunoblot analysis. 26324849 1 82 theme N-linked 351:358 arg1 SIBLINGs 375:382 SIBLINGs 375:382 SIBLINGs 375:382 Recent studies have identified family with sequence similarity member 20C (FAM20C) as a kinase that phosphorylates the Ser in Ser-X-Glu/phospho-Ser (pSer) motifs in the small-integrin-binding ligand N-linked glycoproteins (SIBLINGs). 26324849 1 82 theme N-linked 351:358 arg1 glycoproteins 360:372 the small-integrin-binding ligand N-linked glycoproteins 317:372 the small-integrin-binding ligand N-linked glycoproteins (SIBLINGs) 317:383 Recent studies have identified family with sequence similarity member 20C (FAM20C) as a kinase that phosphorylates the Ser in Ser-X-Glu/phospho-Ser (pSer) motifs in the small-integrin-binding ligand N-linked glycoproteins (SIBLINGs). 26324849 0 83 link N-linked 120:127 arg1 glycoproteins 129:141 the small-integrin-binding ligand N-linked glycoproteins 86:141 the small-integrin-binding ligand N-linked glycoproteins in bone 86:149 Family with sequence similarity member 20C is the primary but not the only kinase for the small-integrin-binding ligand N-linked glycoproteins in bone. 26324849 6 84 theme migration 1000:1008 arg1 Mr 1016:1017 Mr 1016:1017 Mr 1016:1017 On the native gel, the SIBLINGs from KO mice showed a lower migration rate (Mr) than those from the WT. 26324849 6 84 theme migration 1000:1008 arg1 rate 1010:1013 a lower migration rate 992:1013 a lower migration rate (Mr) 992:1018 On the native gel, the SIBLINGs from KO mice showed a lower migration rate (Mr) than those from the WT. 26324849 8 85 theme peptides 1389:1396 arg1 region 1330:1335 the region 1326:1335 the region of the acidic Ser- and aspartate-rich motif (ASARM) peptides 1326:1396 Mass spectrometry identified less pSers in the SIBLINGs from the KO mice [including the region of the acidic Ser- and aspartate-rich motif (ASARM) peptides]. 26324849 9 86 theme intriguing 1406:1415 arg1 finding 1417:1423 an intriguing finding 1403:1423 an intriguing finding 1403:1423 In an intriguing finding, several pSers in the Ser-X-Glu motifs in the KO mice maintained their phosphorylation, whereas several others in non-Ser-X-Glu motifs did not. 26324849 11 87 with Family 1815:1820 arg1 20C 1854:1856 sequence similarity member 20C 1827:1856 sequence similarity member 20C 1827:1856 Our results indicate that FAM20C is the primary, but not the only, kinase for the SIBLINGs.-Yang, X., Yan, W., Tian, Y., Ma, P., Opperman, L. A., Wang, X. Family with sequence similarity member 20C is the primary but not the only kinase for the small-integrin-binding ligand N-linked glycoproteins in bone. 26324849 11 88 theme only 1721:1724 arg1 kinase 1727:1732 kinase 1727:1732 kinase for the SIBLINGs.-Yang, X., Yan, W., Tian, Y., Ma, P., Opperman, L. A., Wang, X. Family with sequence similarity member 20C 1727:1856 Our results indicate that FAM20C is the primary, but not the only, kinase for the SIBLINGs.-Yang, X., Yan, W., Tian, Y., Ma, P., Opperman, L. A., Wang, X. Family with sequence similarity member 20C is the primary but not the only kinase for the small-integrin-binding ligand N-linked glycoproteins in bone. 26324849 11 88 theme only 1721:1724 arg1 FAM20C 1686:1691 FAM20C 1686:1691 FAM20C 1686:1691 Our results indicate that FAM20C is the primary, but not the only, kinase for the SIBLINGs.-Yang, X., Yan, W., Tian, Y., Ma, P., Opperman, L. A., Wang, X. Family with sequence similarity member 20C is the primary but not the only kinase for the small-integrin-binding ligand N-linked glycoproteins in bone. 26324849 0 89 theme similarity 21:30 arg1 20C 39:41 sequence similarity member 20C 12:41 sequence similarity member 20C 12:41 Family with sequence similarity member 20C is the primary but not the only kinase for the small-integrin-binding ligand N-linked glycoproteins in bone. 26324849 8 90 theme Mass 1242:1245 arg1 spectrometry 1247:1258 Mass spectrometry 1242:1258 Mass spectrometry 1242:1258 Mass spectrometry identified less pSers in the SIBLINGs from the KO mice [including the region of the acidic Ser- and aspartate-rich motif (ASARM) peptides]. 26324849 2 91 theme in 398:399 arg1 evidence 406:413 no in vivo evidence 395:413 no in vivo evidence that validates this finding 395:441 There is no in vivo evidence that validates this finding, and it is unclear whether FAM20C is the only kinase for SIBLINGs. 26324849 7 92 theme Calf 1044:1047 arg1 treatment 1071:1079 Calf intestine phosphatase treatment 1044:1079 Calf intestine phosphatase treatment 1044:1079 Calf intestine phosphatase treatment shifted SIBLINGs from the WT mice to the level adjacent to the KO, but failed to shift the latter, suggesting a phosphorylation loss of SIBLINGs in the KO mice. 26324849 11 93 theme ligand 1928:1933 arg1 glycoproteins 1944:1956 the small-integrin-binding ligand N-linked glycoproteins 1901:1956 the small-integrin-binding ligand N-linked glycoproteins in bone 1901:1964 Our results indicate that FAM20C is the primary, but not the only, kinase for the SIBLINGs.-Yang, X., Yan, W., Tian, Y., Ma, P., Opperman, L. A., Wang, X. Family with sequence similarity member 20C is the primary but not the only kinase for the small-integrin-binding ligand N-linked glycoproteins in bone. 26324849 1 94 from motifs 307:312 arg1 SIBLINGs 375:382 SIBLINGs 375:382 SIBLINGs 375:382 Recent studies have identified family with sequence similarity member 20C (FAM20C) as a kinase that phosphorylates the Ser in Ser-X-Glu/phospho-Ser (pSer) motifs in the small-integrin-binding ligand N-linked glycoproteins (SIBLINGs). 26324849 1 94 from motifs 307:312 arg1 glycoproteins 360:372 the small-integrin-binding ligand N-linked glycoproteins 317:372 the small-integrin-binding ligand N-linked glycoproteins (SIBLINGs) 317:383 Recent studies have identified family with sequence similarity member 20C (FAM20C) as a kinase that phosphorylates the Ser in Ser-X-Glu/phospho-Ser (pSer) motifs in the small-integrin-binding ligand N-linked glycoproteins (SIBLINGs). 26324849 2 95 dep in 398:399 arg1 vivo 401:404 vivo 401:404 vivo 401:404 There is no in vivo evidence that validates this finding, and it is unclear whether FAM20C is the only kinase for SIBLINGs. 26324849 0 96 from glycoproteins 129:141 arg1 bone 146:149 bone 146:149 bone 146:149 Family with sequence similarity member 20C is the primary but not the only kinase for the small-integrin-binding ligand N-linked glycoproteins in bone. 26324849 3 97 theme phosphorylation 607:621 arg1 levels 623:628 the phosphorylation levels 603:628 the phosphorylation levels 603:628 We extracted bone noncollagenous proteins (NCPs) from Fam20C-knockout (KO) mice and analyzed the phosphorylation levels. 26324849 4 98 theme anion-exchange 750:763 arg1 chromatography 765:778 anion-exchange chromatography 750:778 anion-exchange chromatography 750:778 The total NCPs were separated into osteopontin-, bone sialoprotein-, and dentin matrix protein-1-enriched fractions by anion-exchange chromatography and analyzed by SDS-PAGE, native PAGE, and Western immunoblot analysis. 28502704 6 0 theme energy 965:970 arg1 status 972:977 energy status 965:977 energy status 965:977 Following these diets, brain (prefrontal cortex) and liver were examined for gene expression levels of key O-GlcNAc mediators, global and protein specific O-GlcNAc as well as indicators of energy status. 28502704 2 1 theme autism 372:377 arg1 ASD 398:400 ASD 398:400 ASD 398:400 Abnormal O-GlcNAc patterning is evident in several neurological disease states including epilepsy, Alzheimer's disease and autism spectrum disorder (ASD). 28502704 2 1 theme autism 372:377 arg1 disorder 388:395 autism spectrum disorder 372:395 autism spectrum disorder (ASD) 372:401 Abnormal O-GlcNAc patterning is evident in several neurological disease states including epilepsy, Alzheimer's disease and autism spectrum disorder (ASD). 28502704 11 2 from fluctuations 1580:1591 arg1 status 1603:1608 energy status 1596:1608 energy status 1596:1608 Although levels of O-GlcNAc play an important role in neurodevelopment, levels of this modification in the juvenile mouse brain were stable with the KD despite large fluctuations in energy status. 28502704 11 3 theme O-GlcNAc 1433:1440 arg1 levels 1423:1428 levels 1423:1428 levels of O-GlcNAc 1423:1440 Although levels of O-GlcNAc play an important role in neurodevelopment, levels of this modification in the juvenile mouse brain were stable with the KD despite large fluctuations in energy status. 28502704 2 4 theme neurological 300:311 arg1 epilepsy 338:345 epilepsy 338:345 epilepsy 338:345 Abnormal O-GlcNAc patterning is evident in several neurological disease states including epilepsy, Alzheimer's disease and autism spectrum disorder (ASD). 28502704 2 4 theme neurological 300:311 arg1 states 321:326 several neurological disease states 292:326 several neurological disease states including epilepsy, Alzheimer's disease and autism spectrum disorder (ASD) 292:401 Abnormal O-GlcNAc patterning is evident in several neurological disease states including epilepsy, Alzheimer's disease and autism spectrum disorder (ASD). 28502704 1 5 theme O-linked-β-N-acetyl 106:124 arg1 modification 173:184 a post-translational modification 152:184 a post-translational modification to Ser/Thr residues that integrates energy supply with demand 152:246 BACKGROUND Protein O-linked-β-N-acetyl glucosamine (O-GlcNAc) is a post-translational modification to Ser/Thr residues that integrates energy supply with demand. 28502704 1 5 theme O-linked-β-N-acetyl 106:124 arg1 O-GlcNAc 139:146 O-GlcNAc 139:146 O-GlcNAc 139:146 BACKGROUND Protein O-linked-β-N-acetyl glucosamine (O-GlcNAc) is a post-translational modification to Ser/Thr residues that integrates energy supply with demand. 28502704 1 5 theme O-linked-β-N-acetyl 106:124 arg1 glucosamine 126:136 BACKGROUND Protein O-linked-β-N-acetyl glucosamine 87:136 BACKGROUND Protein O-linked-β-N-acetyl glucosamine (O-GlcNAc) 87:147 BACKGROUND Protein O-linked-β-N-acetyl glucosamine (O-GlcNAc) is a post-translational modification to Ser/Thr residues that integrates energy supply with demand. 28502704 8 6 theme lower 1093:1097 arg1 levels 1107:1112 lower protein levels 1093:1112 lower protein levels of O-GlcNAc transferase (OGT) and increased O-GlcNAcase (OGA) (p<0.05) 1093:1183 Reductions were likely mediated by lower protein levels of O-GlcNAc transferase (OGT) and increased O-GlcNAcase (OGA) (p<0.05). 28502704 0 7 theme Ketogenic 0:8 arg1 diet 10:13 Ketogenic diet 0:13 Ketogenic diet 0:13 Ketogenic diet leads to O-GlcNAc modification in the BTBRT+tf/j mouse model of autism. 28502704 12 8 theme ASD 1708:1710 arg1 model 1699:1703 the BTBR model 1690:1703 the BTBR model of ASD 1690:1710 This suggests that it is unlikely that the KD exerts it therapeutic benefit in the BTBR model of ASD by O-GlcNAc related pathways. 28502704 12 9 theme O-GlcNAc 1715:1722 arg1 pathways 1732:1739 O-GlcNAc related pathways 1715:1739 O-GlcNAc related pathways 1715:1739 This suggests that it is unlikely that the KD exerts it therapeutic benefit in the BTBR model of ASD by O-GlcNAc related pathways. 28502704 4 10 theme BTBR 617:620 arg1 model 629:633 the BTBRT+tf/j (BTBR) mouse model 601:633 the BTBRT+tf/j (BTBR) mouse model of ASD 601:640 The goal of this study was to determine whether the KD induces changes in O-GlcNAc in the BTBRT+tf/j (BTBR) mouse model of ASD. 28502704 7 11 dep reduced 995:1001 arg1 p<0.05 1049:1054 p<0.05 1049:1054 p<0.05 1049:1054 RESULTS The KD reduced global O-GlcNAc in the livers of all animals (p<0.05). 28502704 5 12 theme 75 747:748 arg1 % 749:749 % 749:749 % 749:749 METHODS Juvenile male (5weeks), age-matched C57 or BTBR mice consumed a chow diet (13% kcal fat) or KD (75% kcal fat) for 10-14days. 28502704 4 13 theme mouse 623:627 arg1 model 629:633 the BTBRT+tf/j (BTBR) mouse model 601:633 the BTBRT+tf/j (BTBR) mouse model of ASD 601:640 The goal of this study was to determine whether the KD induces changes in O-GlcNAc in the BTBRT+tf/j (BTBR) mouse model of ASD. 28502704 10 14 theme specific 1384:1391 arg1 impacts 1393:1399 tissue specific impacts 1377:1399 tissue specific impacts 1377:1399 CONCLUSIONS The KD has tissue specific impacts on O-GlcNAc. 28502704 5 15 theme age-matched 675:685 arg1 mice 699:702 age-matched C57 or BTBR mice 675:702 age-matched C57 or BTBR mice 675:702 METHODS Juvenile male (5weeks), age-matched C57 or BTBR mice consumed a chow diet (13% kcal fat) or KD (75% kcal fat) for 10-14days. 28502704 4 16 from changes 578:584 arg1 O-GlcNAc 589:596 O-GlcNAc 589:596 O-GlcNAc 589:596 The goal of this study was to determine whether the KD induces changes in O-GlcNAc in the BTBRT+tf/j (BTBR) mouse model of ASD. 28502704 5 17 theme kcal 751:754 arg1 fat 756:758 75% kcal fat 747:758 75% kcal fat 747:758 METHODS Juvenile male (5weeks), age-matched C57 or BTBR mice consumed a chow diet (13% kcal fat) or KD (75% kcal fat) for 10-14days. 28502704 5 17 theme kcal 751:754 arg1 diet 720:723 a chow diet 713:723 a chow diet (13% kcal fat) 713:738 METHODS Juvenile male (5weeks), age-matched C57 or BTBR mice consumed a chow diet (13% kcal fat) or KD (75% kcal fat) for 10-14days. 28502704 5 18 theme Juvenile 651:658 arg1 male 660:663 Juvenile male 651:663 METHODS Juvenile male (5weeks) 643:672 METHODS Juvenile male (5weeks), age-matched C57 or BTBR mice consumed a chow diet (13% kcal fat) or KD (75% kcal fat) for 10-14days. 28502704 5 18 theme Juvenile 651:658 arg1 5weeks 666:671 5weeks 666:671 5weeks 666:671 METHODS Juvenile male (5weeks), age-matched C57 or BTBR mice consumed a chow diet (13% kcal fat) or KD (75% kcal fat) for 10-14days. 28502704 8 19 theme increased 1148:1156 arg1 OGA 1171:1173 OGA 1171:1173 OGA 1171:1173 Reductions were likely mediated by lower protein levels of O-GlcNAc transferase (OGT) and increased O-GlcNAcase (OGA) (p<0.05). 28502704 8 19 theme increased 1148:1156 arg1 p<0.05 1177:1182 p<0.05 1177:1182 p<0.05 1177:1182 Reductions were likely mediated by lower protein levels of O-GlcNAc transferase (OGT) and increased O-GlcNAcase (OGA) (p<0.05). 28502704 8 19 theme increased 1148:1156 arg1 O-GlcNAcase 1158:1168 increased O-GlcNAcase 1148:1168 increased O-GlcNAcase (OGA) (p<0.05) 1148:1183 Reductions were likely mediated by lower protein levels of O-GlcNAc transferase (OGT) and increased O-GlcNAcase (OGA) (p<0.05). 28502704 0 20 theme BTBRT+tf/j 53:62 arg1 model 70:74 the BTBRT+tf/j mouse model 49:74 the BTBRT+tf/j mouse model of autism 49:84 Ketogenic diet leads to O-GlcNAc modification in the BTBRT+tf/j mouse model of autism. 28502704 2 21 theme O-GlcNAc 258:265 arg1 patterning 267:276 Abnormal O-GlcNAc patterning 249:276 Abnormal O-GlcNAc patterning 249:276 Abnormal O-GlcNAc patterning is evident in several neurological disease states including epilepsy, Alzheimer's disease and autism spectrum disorder (ASD). 28502704 6 22 theme O-GlcNAc 883:890 arg1 mediators 892:900 key O-GlcNAc mediators 879:900 key O-GlcNAc mediators 879:900 Following these diets, brain (prefrontal cortex) and liver were examined for gene expression levels of key O-GlcNAc mediators, global and protein specific O-GlcNAc as well as indicators of energy status. 28502704 11 23 from levels 1486:1491 arg1 brain 1536:1540 the juvenile mouse brain 1517:1540 the juvenile mouse brain 1517:1540 Although levels of O-GlcNAc play an important role in neurodevelopment, levels of this modification in the juvenile mouse brain were stable with the KD despite large fluctuations in energy status. 28502704 1 24 theme post-translational 154:171 arg1 modification 173:184 a post-translational modification 152:184 a post-translational modification to Ser/Thr residues that integrates energy supply with demand 152:246 BACKGROUND Protein O-linked-β-N-acetyl glucosamine (O-GlcNAc) is a post-translational modification to Ser/Thr residues that integrates energy supply with demand. 28502704 1 24 theme post-translational 154:171 arg1 glucosamine 126:136 BACKGROUND Protein O-linked-β-N-acetyl glucosamine 87:136 BACKGROUND Protein O-linked-β-N-acetyl glucosamine (O-GlcNAc) 87:147 BACKGROUND Protein O-linked-β-N-acetyl glucosamine (O-GlcNAc) is a post-translational modification to Ser/Thr residues that integrates energy supply with demand. 28502704 11 25 theme juvenile 1521:1528 arg1 brain 1536:1540 the juvenile mouse brain 1517:1540 the juvenile mouse brain 1517:1540 Although levels of O-GlcNAc play an important role in neurodevelopment, levels of this modification in the juvenile mouse brain were stable with the KD despite large fluctuations in energy status. 28502704 0 26 theme autism 79:84 arg1 model 70:74 the BTBRT+tf/j mouse model 49:74 the BTBRT+tf/j mouse model of autism 49:84 Ketogenic diet leads to O-GlcNAc modification in the BTBRT+tf/j mouse model of autism. 28502704 12 27 theme therapeutic 1667:1677 arg1 benefit 1679:1685 therapeutic benefit 1667:1685 it therapeutic benefit 1664:1685 This suggests that it is unlikely that the KD exerts it therapeutic benefit in the BTBR model of ASD by O-GlcNAc related pathways. 28502704 9 28 theme C57 1323:1325 arg1 p<0.05 1345:1350 p<0.05 1345:1350 p<0.05 1345:1350 In contrast, no differences in global O-GlcNAc were noted in the brain (p>0.05), yet OGT and OGA expression (mRNA) were elevated in both C57 and BTBR animals (p<0.05). 28502704 9 28 theme C57 1323:1325 arg1 animals 1336:1342 both C57 and BTBR animals 1318:1342 both C57 and BTBR animals (p<0.05) 1318:1351 In contrast, no differences in global O-GlcNAc were noted in the brain (p>0.05), yet OGT and OGA expression (mRNA) were elevated in both C57 and BTBR animals (p<0.05). 28502704 6 29 theme expression 858:867 arg1 levels 869:874 gene expression levels 853:874 gene expression levels of key O-GlcNAc mediators, global and protein specific O-GlcNAc as well as indicators of energy status 853:977 Following these diets, brain (prefrontal cortex) and liver were examined for gene expression levels of key O-GlcNAc mediators, global and protein specific O-GlcNAc as well as indicators of energy status. 28502704 5 30 dep METHODS 643:649 arg1 male 660:663 Juvenile male 651:663 METHODS Juvenile male (5weeks) 643:672 METHODS Juvenile male (5weeks), age-matched C57 or BTBR mice consumed a chow diet (13% kcal fat) or KD (75% kcal fat) for 10-14days. 28502704 5 30 dep METHODS 643:649 arg1 5weeks 666:671 5weeks 666:671 5weeks 666:671 METHODS Juvenile male (5weeks), age-matched C57 or BTBR mice consumed a chow diet (13% kcal fat) or KD (75% kcal fat) for 10-14days. 28502704 11 31 with stable 1547:1552 arg1 KD 1563:1564 the KD 1559:1564 the KD 1559:1564 Although levels of O-GlcNAc play an important role in neurodevelopment, levels of this modification in the juvenile mouse brain were stable with the KD despite large fluctuations in energy status. 28502704 9 32 theme BTBR 1331:1334 arg1 p<0.05 1345:1350 p<0.05 1345:1350 p<0.05 1345:1350 In contrast, no differences in global O-GlcNAc were noted in the brain (p>0.05), yet OGT and OGA expression (mRNA) were elevated in both C57 and BTBR animals (p<0.05). 28502704 9 32 theme BTBR 1331:1334 arg1 animals 1336:1342 both C57 and BTBR animals 1318:1342 both C57 and BTBR animals (p<0.05) 1318:1351 In contrast, no differences in global O-GlcNAc were noted in the brain (p>0.05), yet OGT and OGA expression (mRNA) were elevated in both C57 and BTBR animals (p<0.05). 28502704 7 33 theme animals 1040:1046 arg1 livers 1026:1031 the livers 1022:1031 the livers of all animals 1022:1046 RESULTS The KD reduced global O-GlcNAc in the livers of all animals (p<0.05). 28502704 1 34 theme Protein 98:104 arg1 modification 173:184 a post-translational modification 152:184 a post-translational modification to Ser/Thr residues that integrates energy supply with demand 152:246 BACKGROUND Protein O-linked-β-N-acetyl glucosamine (O-GlcNAc) is a post-translational modification to Ser/Thr residues that integrates energy supply with demand. 28502704 1 34 theme Protein 98:104 arg1 O-GlcNAc 139:146 O-GlcNAc 139:146 O-GlcNAc 139:146 BACKGROUND Protein O-linked-β-N-acetyl glucosamine (O-GlcNAc) is a post-translational modification to Ser/Thr residues that integrates energy supply with demand. 28502704 1 34 theme Protein 98:104 arg1 glucosamine 126:136 BACKGROUND Protein O-linked-β-N-acetyl glucosamine 87:136 BACKGROUND Protein O-linked-β-N-acetyl glucosamine (O-GlcNAc) 87:147 BACKGROUND Protein O-linked-β-N-acetyl glucosamine (O-GlcNAc) is a post-translational modification to Ser/Thr residues that integrates energy supply with demand. 28502704 2 35 from evident 281:287 arg1 epilepsy 338:345 epilepsy 338:345 epilepsy 338:345 Abnormal O-GlcNAc patterning is evident in several neurological disease states including epilepsy, Alzheimer's disease and autism spectrum disorder (ASD). 28502704 2 35 from evident 281:287 arg1 states 321:326 several neurological disease states 292:326 several neurological disease states including epilepsy, Alzheimer's disease and autism spectrum disorder (ASD) 292:401 Abnormal O-GlcNAc patterning is evident in several neurological disease states including epilepsy, Alzheimer's disease and autism spectrum disorder (ASD). 28502704 6 36 theme specific 922:929 arg1 O-GlcNAc 931:938 global and protein specific O-GlcNAc 903:938 global and protein specific O-GlcNAc 903:938 Following these diets, brain (prefrontal cortex) and liver were examined for gene expression levels of key O-GlcNAc mediators, global and protein specific O-GlcNAc as well as indicators of energy status. 28502704 3 37 theme high-fat 466:473 arg1 KD 510:511 KD 510:511 KD 510:511 A potential treatment option for these disorders includes the high-fat, low-carbohydrate, ketogenic diet (KD). 28502704 3 37 theme high-fat 466:473 arg1 diet 504:507 the high-fat, low-carbohydrate, ketogenic diet 462:507 the high-fat, low-carbohydrate, ketogenic diet (KD) 462:512 A potential treatment option for these disorders includes the high-fat, low-carbohydrate, ketogenic diet (KD). 28502704 0 38 theme O-GlcNAc 24:31 arg1 modification 33:44 O-GlcNAc modification 24:44 O-GlcNAc modification 24:44 Ketogenic diet leads to O-GlcNAc modification in the BTBRT+tf/j mouse model of autism. 28502704 5 39 theme 13 726:727 arg1 % 728:728 % 728:728 % 728:728 METHODS Juvenile male (5weeks), age-matched C57 or BTBR mice consumed a chow diet (13% kcal fat) or KD (75% kcal fat) for 10-14days. 28502704 3 40 theme potential 406:414 arg1 option 426:431 A potential treatment option 404:431 A potential treatment option for these disorders 404:451 A potential treatment option for these disorders includes the high-fat, low-carbohydrate, ketogenic diet (KD). 28502704 11 41 theme important 1450:1458 arg1 role 1460:1463 an important role 1447:1463 an important role 1447:1463 Although levels of O-GlcNAc play an important role in neurodevelopment, levels of this modification in the juvenile mouse brain were stable with the KD despite large fluctuations in energy status. 28502704 5 42 theme kcal 730:733 arg1 fat 735:737 13% kcal fat 726:737 13% kcal fat 726:737 METHODS Juvenile male (5weeks), age-matched C57 or BTBR mice consumed a chow diet (13% kcal fat) or KD (75% kcal fat) for 10-14days. 28502704 5 42 theme kcal 730:733 arg1 diet 720:723 a chow diet 713:723 a chow diet (13% kcal fat) 713:738 METHODS Juvenile male (5weeks), age-matched C57 or BTBR mice consumed a chow diet (13% kcal fat) or KD (75% kcal fat) for 10-14days. 28502704 4 43 theme study 532:536 arg1 goal 519:522 The goal 515:522 The goal of this study 515:536 The goal of this study was to determine whether the KD induces changes in O-GlcNAc in the BTBRT+tf/j (BTBR) mouse model of ASD. 28502704 11 44 theme energy 1596:1601 arg1 status 1603:1608 energy status 1596:1608 energy status 1596:1608 Although levels of O-GlcNAc play an important role in neurodevelopment, levels of this modification in the juvenile mouse brain were stable with the KD despite large fluctuations in energy status. 28502704 9 45 theme global 1217:1222 arg1 O-GlcNAc 1224:1231 global O-GlcNAc 1217:1231 global O-GlcNAc 1217:1231 In contrast, no differences in global O-GlcNAc were noted in the brain (p>0.05), yet OGT and OGA expression (mRNA) were elevated in both C57 and BTBR animals (p<0.05). 28502704 5 46 theme % 728:728 arg1 fat 735:737 13% kcal fat 726:737 13% kcal fat 726:737 METHODS Juvenile male (5weeks), age-matched C57 or BTBR mice consumed a chow diet (13% kcal fat) or KD (75% kcal fat) for 10-14days. 28502704 5 46 theme % 728:728 arg1 diet 720:723 a chow diet 713:723 a chow diet (13% kcal fat) 713:738 METHODS Juvenile male (5weeks), age-matched C57 or BTBR mice consumed a chow diet (13% kcal fat) or KD (75% kcal fat) for 10-14days. 28502704 6 47 theme prefrontal 806:815 arg1 brain 799:803 brain 799:803 brain (prefrontal cortex) 799:823 Following these diets, brain (prefrontal cortex) and liver were examined for gene expression levels of key O-GlcNAc mediators, global and protein specific O-GlcNAc as well as indicators of energy status. 28502704 6 47 theme prefrontal 806:815 arg1 cortex 817:822 prefrontal cortex 806:822 prefrontal cortex 806:822 Following these diets, brain (prefrontal cortex) and liver were examined for gene expression levels of key O-GlcNAc mediators, global and protein specific O-GlcNAc as well as indicators of energy status. 28502704 6 48 theme status 972:977 arg1 mediators 892:900 key O-GlcNAc mediators 879:900 key O-GlcNAc mediators 879:900 Following these diets, brain (prefrontal cortex) and liver were examined for gene expression levels of key O-GlcNAc mediators, global and protein specific O-GlcNAc as well as indicators of energy status. 28502704 6 48 theme status 972:977 arg1 O-GlcNAc 931:938 global and protein specific O-GlcNAc 903:938 global and protein specific O-GlcNAc 903:938 Following these diets, brain (prefrontal cortex) and liver were examined for gene expression levels of key O-GlcNAc mediators, global and protein specific O-GlcNAc as well as indicators of energy status. 28502704 6 48 theme status 972:977 arg1 indicators 951:960 indicators 951:960 indicators of energy status 951:977 Following these diets, brain (prefrontal cortex) and liver were examined for gene expression levels of key O-GlcNAc mediators, global and protein specific O-GlcNAc as well as indicators of energy status. 28502704 2 49 theme spectrum 379:386 arg1 ASD 398:400 ASD 398:400 ASD 398:400 Abnormal O-GlcNAc patterning is evident in several neurological disease states including epilepsy, Alzheimer's disease and autism spectrum disorder (ASD). 28502704 2 49 theme spectrum 379:386 arg1 disorder 388:395 autism spectrum disorder 372:395 autism spectrum disorder (ASD) 372:401 Abnormal O-GlcNAc patterning is evident in several neurological disease states including epilepsy, Alzheimer's disease and autism spectrum disorder (ASD). 28502704 2 50 theme disease 313:319 arg1 epilepsy 338:345 epilepsy 338:345 epilepsy 338:345 Abnormal O-GlcNAc patterning is evident in several neurological disease states including epilepsy, Alzheimer's disease and autism spectrum disorder (ASD). 28502704 2 50 theme disease 313:319 arg1 states 321:326 several neurological disease states 292:326 several neurological disease states including epilepsy, Alzheimer's disease and autism spectrum disorder (ASD) 292:401 Abnormal O-GlcNAc patterning is evident in several neurological disease states including epilepsy, Alzheimer's disease and autism spectrum disorder (ASD). 28502704 12 51 theme related 1724:1730 arg1 pathways 1732:1739 O-GlcNAc related pathways 1715:1739 O-GlcNAc related pathways 1715:1739 This suggests that it is unlikely that the KD exerts it therapeutic benefit in the BTBR model of ASD by O-GlcNAc related pathways. 28502704 10 52 dep CONCLUSIONS 1354:1364 arg1 has 1373:1375 has 1373:1375 has tissue specific impacts on O-GlcNAc 1373:1411 CONCLUSIONS The KD has tissue specific impacts on O-GlcNAc. 28502704 2 53 theme several 292:298 arg1 epilepsy 338:345 epilepsy 338:345 epilepsy 338:345 Abnormal O-GlcNAc patterning is evident in several neurological disease states including epilepsy, Alzheimer's disease and autism spectrum disorder (ASD). 28502704 2 53 theme several 292:298 arg1 states 321:326 several neurological disease states 292:326 several neurological disease states including epilepsy, Alzheimer's disease and autism spectrum disorder (ASD) 292:401 Abnormal O-GlcNAc patterning is evident in several neurological disease states including epilepsy, Alzheimer's disease and autism spectrum disorder (ASD). 28502704 7 54 dep RESULTS 980:986 arg1 reduced 995:1001 reduced 995:1001 reduced global O-GlcNAc in the livers of all animals (p<0.05) 995:1055 RESULTS The KD reduced global O-GlcNAc in the livers of all animals (p<0.05). 28502704 1 55 theme Ser/Thr 189:195 arg1 residues 197:204 Ser/Thr residues 189:204 Ser/Thr residues 189:204 BACKGROUND Protein O-linked-β-N-acetyl glucosamine (O-GlcNAc) is a post-translational modification to Ser/Thr residues that integrates energy supply with demand. 28502704 6 56 theme gene 853:856 arg1 levels 869:874 gene expression levels 853:874 gene expression levels of key O-GlcNAc mediators, global and protein specific O-GlcNAc as well as indicators of energy status 853:977 Following these diets, brain (prefrontal cortex) and liver were examined for gene expression levels of key O-GlcNAc mediators, global and protein specific O-GlcNAc as well as indicators of energy status. 28502704 4 57 theme ASD 638:640 arg1 model 629:633 the BTBRT+tf/j (BTBR) mouse model 601:633 the BTBRT+tf/j (BTBR) mouse model of ASD 601:640 The goal of this study was to determine whether the KD induces changes in O-GlcNAc in the BTBRT+tf/j (BTBR) mouse model of ASD. 28502704 2 58 theme Abnormal 249:256 arg1 patterning 267:276 Abnormal O-GlcNAc patterning 249:276 Abnormal O-GlcNAc patterning 249:276 Abnormal O-GlcNAc patterning is evident in several neurological disease states including epilepsy, Alzheimer's disease and autism spectrum disorder (ASD). 28502704 8 59 theme protein 1099:1105 arg1 levels 1107:1112 lower protein levels 1093:1112 lower protein levels of O-GlcNAc transferase (OGT) and increased O-GlcNAcase (OGA) (p<0.05) 1093:1183 Reductions were likely mediated by lower protein levels of O-GlcNAc transferase (OGT) and increased O-GlcNAcase (OGA) (p<0.05). 28502704 5 60 theme % 749:749 arg1 fat 756:758 75% kcal fat 747:758 75% kcal fat 747:758 METHODS Juvenile male (5weeks), age-matched C57 or BTBR mice consumed a chow diet (13% kcal fat) or KD (75% kcal fat) for 10-14days. 28502704 5 60 theme % 749:749 arg1 diet 720:723 a chow diet 713:723 a chow diet (13% kcal fat) 713:738 METHODS Juvenile male (5weeks), age-matched C57 or BTBR mice consumed a chow diet (13% kcal fat) or KD (75% kcal fat) for 10-14days. 28502704 8 61 theme transferase 1126:1136 arg1 levels 1107:1112 lower protein levels 1093:1112 lower protein levels of O-GlcNAc transferase (OGT) and increased O-GlcNAcase (OGA) (p<0.05) 1093:1183 Reductions were likely mediated by lower protein levels of O-GlcNAc transferase (OGT) and increased O-GlcNAcase (OGA) (p<0.05). 28502704 10 62 theme tissue 1377:1382 arg1 impacts 1393:1399 tissue specific impacts 1377:1399 tissue specific impacts 1377:1399 CONCLUSIONS The KD has tissue specific impacts on O-GlcNAc. 28502704 9 63 theme OGA 1279:1281 arg1 mRNA 1295:1298 mRNA 1295:1298 mRNA 1295:1298 In contrast, no differences in global O-GlcNAc were noted in the brain (p>0.05), yet OGT and OGA expression (mRNA) were elevated in both C57 and BTBR animals (p<0.05). 28502704 9 63 theme OGA 1279:1281 arg1 expression 1283:1292 OGA expression 1279:1292 OGA expression (mRNA) 1279:1299 In contrast, no differences in global O-GlcNAc were noted in the brain (p>0.05), yet OGT and OGA expression (mRNA) were elevated in both C57 and BTBR animals (p<0.05). 28502704 12 64 theme BTBR 1694:1697 arg1 model 1699:1703 the BTBR model 1690:1703 the BTBR model of ASD 1690:1710 This suggests that it is unlikely that the KD exerts it therapeutic benefit in the BTBR model of ASD by O-GlcNAc related pathways. 28502704 11 65 theme large 1574:1578 arg1 fluctuations 1580:1591 large fluctuations 1574:1591 large fluctuations in energy status 1574:1608 Although levels of O-GlcNAc play an important role in neurodevelopment, levels of this modification in the juvenile mouse brain were stable with the KD despite large fluctuations in energy status. 28502704 3 66 dep high-fat 466:473 arg1 ketogenic 494:502 ketogenic 494:502 ketogenic 494:502 A potential treatment option for these disorders includes the high-fat, low-carbohydrate, ketogenic diet (KD). 28502704 3 66 dep high-fat 466:473 arg1 low-carbohydrate 476:491 low-carbohydrate 476:491 low-carbohydrate 476:491 A potential treatment option for these disorders includes the high-fat, low-carbohydrate, ketogenic diet (KD). 28502704 6 67 theme global 903:908 arg1 O-GlcNAc 931:938 global and protein specific O-GlcNAc 903:938 global and protein specific O-GlcNAc 903:938 Following these diets, brain (prefrontal cortex) and liver were examined for gene expression levels of key O-GlcNAc mediators, global and protein specific O-GlcNAc as well as indicators of energy status. 28502704 0 68 theme mouse 64:68 arg1 model 70:74 the BTBRT+tf/j mouse model 49:74 the BTBRT+tf/j mouse model of autism 49:84 Ketogenic diet leads to O-GlcNAc modification in the BTBRT+tf/j mouse model of autism. 28502704 8 69 theme O-GlcNAc 1117:1124 arg1 OGT 1139:1141 OGT 1139:1141 OGT 1139:1141 Reductions were likely mediated by lower protein levels of O-GlcNAc transferase (OGT) and increased O-GlcNAcase (OGA) (p<0.05). 28502704 8 69 theme O-GlcNAc 1117:1124 arg1 transferase 1126:1136 O-GlcNAc transferase 1117:1136 O-GlcNAc transferase (OGT) 1117:1142 Reductions were likely mediated by lower protein levels of O-GlcNAc transferase (OGT) and increased O-GlcNAcase (OGA) (p<0.05). 28502704 6 70 theme mediators 892:900 arg1 levels 869:874 gene expression levels 853:874 gene expression levels of key O-GlcNAc mediators, global and protein specific O-GlcNAc as well as indicators of energy status 853:977 Following these diets, brain (prefrontal cortex) and liver were examined for gene expression levels of key O-GlcNAc mediators, global and protein specific O-GlcNAc as well as indicators of energy status. 28502704 8 71 theme O-GlcNAcase 1158:1168 arg1 levels 1107:1112 lower protein levels 1093:1112 lower protein levels of O-GlcNAc transferase (OGT) and increased O-GlcNAcase (OGA) (p<0.05) 1093:1183 Reductions were likely mediated by lower protein levels of O-GlcNAc transferase (OGT) and increased O-GlcNAcase (OGA) (p<0.05). 28502704 11 72 theme modification 1501:1512 arg1 levels 1486:1491 levels 1486:1491 levels of this modification in the juvenile mouse brain 1486:1540 Although levels of O-GlcNAc play an important role in neurodevelopment, levels of this modification in the juvenile mouse brain were stable with the KD despite large fluctuations in energy status. 28502704 5 73 theme chow 715:718 arg1 fat 756:758 75% kcal fat 747:758 75% kcal fat 747:758 METHODS Juvenile male (5weeks), age-matched C57 or BTBR mice consumed a chow diet (13% kcal fat) or KD (75% kcal fat) for 10-14days. 28502704 5 73 theme chow 715:718 arg1 fat 735:737 13% kcal fat 726:737 13% kcal fat 726:737 METHODS Juvenile male (5weeks), age-matched C57 or BTBR mice consumed a chow diet (13% kcal fat) or KD (75% kcal fat) for 10-14days. 28502704 5 73 theme chow 715:718 arg1 diet 720:723 a chow diet 713:723 a chow diet (13% kcal fat) 713:738 METHODS Juvenile male (5weeks), age-matched C57 or BTBR mice consumed a chow diet (13% kcal fat) or KD (75% kcal fat) for 10-14days. 28502704 2 74 from states 321:326 arg1 evident 281:287 evident 281:287 evident 281:287 Abnormal O-GlcNAc patterning is evident in several neurological disease states including epilepsy, Alzheimer's disease and autism spectrum disorder (ASD). 28502704 6 75 theme key 879:881 arg1 mediators 892:900 key O-GlcNAc mediators 879:900 key O-GlcNAc mediators 879:900 Following these diets, brain (prefrontal cortex) and liver were examined for gene expression levels of key O-GlcNAc mediators, global and protein specific O-GlcNAc as well as indicators of energy status. 28502704 5 76 theme C57 687:689 arg1 mice 699:702 age-matched C57 or BTBR mice 675:702 age-matched C57 or BTBR mice 675:702 METHODS Juvenile male (5weeks), age-matched C57 or BTBR mice consumed a chow diet (13% kcal fat) or KD (75% kcal fat) for 10-14days. 28502704 11 77 theme mouse 1530:1534 arg1 brain 1536:1540 the juvenile mouse brain 1517:1540 the juvenile mouse brain 1517:1540 Although levels of O-GlcNAc play an important role in neurodevelopment, levels of this modification in the juvenile mouse brain were stable with the KD despite large fluctuations in energy status. 28502704 5 78 theme BTBR 694:697 arg1 mice 699:702 age-matched C57 or BTBR mice 675:702 age-matched C57 or BTBR mice 675:702 METHODS Juvenile male (5weeks), age-matched C57 or BTBR mice consumed a chow diet (13% kcal fat) or KD (75% kcal fat) for 10-14days. 28502704 6 79 theme indicators 951:960 arg1 levels 869:874 gene expression levels 853:874 gene expression levels of key O-GlcNAc mediators, global and protein specific O-GlcNAc as well as indicators of energy status 853:977 Following these diets, brain (prefrontal cortex) and liver were examined for gene expression levels of key O-GlcNAc mediators, global and protein specific O-GlcNAc as well as indicators of energy status. 28502704 1 80 theme BACKGROUND 87:96 arg1 modification 173:184 a post-translational modification 152:184 a post-translational modification to Ser/Thr residues that integrates energy supply with demand 152:246 BACKGROUND Protein O-linked-β-N-acetyl glucosamine (O-GlcNAc) is a post-translational modification to Ser/Thr residues that integrates energy supply with demand. 28502704 1 80 theme BACKGROUND 87:96 arg1 O-GlcNAc 139:146 O-GlcNAc 139:146 O-GlcNAc 139:146 BACKGROUND Protein O-linked-β-N-acetyl glucosamine (O-GlcNAc) is a post-translational modification to Ser/Thr residues that integrates energy supply with demand. 28502704 1 80 theme BACKGROUND 87:96 arg1 glucosamine 126:136 BACKGROUND Protein O-linked-β-N-acetyl glucosamine 87:136 BACKGROUND Protein O-linked-β-N-acetyl glucosamine (O-GlcNAc) 87:147 BACKGROUND Protein O-linked-β-N-acetyl glucosamine (O-GlcNAc) is a post-translational modification to Ser/Thr residues that integrates energy supply with demand. 28502704 6 81 theme O-GlcNAc 931:938 arg1 levels 869:874 gene expression levels 853:874 gene expression levels of key O-GlcNAc mediators, global and protein specific O-GlcNAc as well as indicators of energy status 853:977 Following these diets, brain (prefrontal cortex) and liver were examined for gene expression levels of key O-GlcNAc mediators, global and protein specific O-GlcNAc as well as indicators of energy status. 28502704 1 82 theme energy 222:227 arg1 supply 229:234 energy supply 222:234 energy supply 222:234 BACKGROUND Protein O-linked-β-N-acetyl glucosamine (O-GlcNAc) is a post-translational modification to Ser/Thr residues that integrates energy supply with demand. 28502704 7 83 theme global 1003:1008 arg1 O-GlcNAc 1010:1017 global O-GlcNAc 1003:1017 global O-GlcNAc 1003:1017 RESULTS The KD reduced global O-GlcNAc in the livers of all animals (p<0.05). 28502704 3 84 theme treatment 416:424 arg1 option 426:431 A potential treatment option 404:431 A potential treatment option for these disorders 404:451 A potential treatment option for these disorders includes the high-fat, low-carbohydrate, ketogenic diet (KD). 28502704 9 85 from differences 1202:1212 arg1 O-GlcNAc 1224:1231 global O-GlcNAc 1217:1231 global O-GlcNAc 1217:1231 In contrast, no differences in global O-GlcNAc were noted in the brain (p>0.05), yet OGT and OGA expression (mRNA) were elevated in both C57 and BTBR animals (p<0.05). 28502704 10 86 contain has 1373:1375 arg2 impacts 1393:1399 tissue specific impacts 1377:1399 tissue specific impacts 1377:1399 CONCLUSIONS The KD has tissue specific impacts on O-GlcNAc. 28502704 10 86 contain has 1373:1375 arg1 KD 1370:1371 The KD 1366:1371 The KD 1366:1371 CONCLUSIONS The KD has tissue specific impacts on O-GlcNAc. 28502704 4 87 theme BTBRT+tf/j 605:614 arg1 model 629:633 the BTBRT+tf/j (BTBR) mouse model 601:633 the BTBRT+tf/j (BTBR) mouse model of ASD 601:640 The goal of this study was to determine whether the KD induces changes in O-GlcNAc in the BTBRT+tf/j (BTBR) mouse model of ASD. 28502704 12 88 dep it 1664:1665 arg1 benefit 1679:1685 therapeutic benefit 1667:1685 it therapeutic benefit 1664:1685 This suggests that it is unlikely that the KD exerts it therapeutic benefit in the BTBR model of ASD by O-GlcNAc related pathways. 28611761 10 0 theme Carbohydrate 2056:2067 arg1 " 2079:2079 "Carbohydrate metabolism" 2055:2079 "Carbohydrate metabolism" 2055:2079 The predicted colonic microbial function showed an enrichment of "Energy metabolism" and "Carbohydrate metabolism" pathways in mice from group G and M, suggesting that the altered bacterial community in the colon of mice with the two dietary fibers probably resulted in a more efficient degradation of dietary polysaccharides. 28611761 10 1 from M 2115:2115 arg1 mice 2093:2096 mice 2093:2096 mice from group G and M 2093:2115 The predicted colonic microbial function showed an enrichment of "Energy metabolism" and "Carbohydrate metabolism" pathways in mice from group G and M, suggesting that the altered bacterial community in the colon of mice with the two dietary fibers probably resulted in a more efficient degradation of dietary polysaccharides. 28611761 10 1 from M 2115:2115 arg1 enrichment 2017:2026 an enrichment 2014:2026 an enrichment of "Energy metabolism" and "Carbohydrate metabolism" pathways in mice from group G and M 2014:2115 The predicted colonic microbial function showed an enrichment of "Energy metabolism" and "Carbohydrate metabolism" pathways in mice from group G and M, suggesting that the altered bacterial community in the colon of mice with the two dietary fibers probably resulted in a more efficient degradation of dietary polysaccharides. 28611761 9 2 theme pathogenic 1899:1908 arg1 bacteria 1910:1917 conditional pathogenic bacteria 1887:1917 conditional pathogenic bacteria in mice fed dietary β-glucan in current study 1887:1963 The relative abundance of bacteria from the three classes of Proteobacteria, Betaproteobacteria, Gammaproteobacteria (including Enterobacteriaceae) and Deltaproteobacteria, were significantly more abundant in group G, indicating a higher ratio of conditional pathogenic bacteria in mice fed dietary β-glucan in current study. 28611761 9 3 theme bacteria 1910:1917 arg1 ratio 1878:1882 a higher ratio 1869:1882 a higher ratio of conditional pathogenic bacteria in mice fed dietary β-glucan in current study 1869:1963 The relative abundance of bacteria from the three classes of Proteobacteria, Betaproteobacteria, Gammaproteobacteria (including Enterobacteriaceae) and Deltaproteobacteria, were significantly more abundant in group G, indicating a higher ratio of conditional pathogenic bacteria in mice fed dietary β-glucan in current study. 28611761 8 4 theme p 1629:1629 arg1 GM 1625:1626 group GM 1619:1626 group GM (p < 0.05) 1619:1637 In contrast, Adlercreutzia, Odoribacter, and Coprococcus were significantly more abundant in group M, whereas Oscillospira, Desulfovibrio, and Ruminoccaceae, typical hydrogenotrophs equipped with multiple carbohydrate active enzymes, were remarkably enriched in group GM (p < 0.05). 28611761 8 4 theme p 1629:1629 arg1 < 1631:1631 p < 0.05 1629:1636 p < 0.05 1629:1636 In contrast, Adlercreutzia, Odoribacter, and Coprococcus were significantly more abundant in group M, whereas Oscillospira, Desulfovibrio, and Ruminoccaceae, typical hydrogenotrophs equipped with multiple carbohydrate active enzymes, were remarkably enriched in group GM (p < 0.05). 28611761 2 5 theme microcrystalline 495:510 arg1 cellulose 512:520 microcrystalline cellulose 495:520 microcrystalline cellulose (M) as IDF 495:531 Thus, bacterial community composition and function in the colon of BALB/c mice (n = 7) fed with a high level (approximately 20%) of typical SDF, oat-derived β-glucan (G), microcrystalline cellulose (M) as IDF, or their mixture (GM), were compared. 28611761 2 5 theme microcrystalline 495:510 arg1 SDF 464:466 typical SDF 456:466 typical SDF 456:466 Thus, bacterial community composition and function in the colon of BALB/c mice (n = 7) fed with a high level (approximately 20%) of typical SDF, oat-derived β-glucan (G), microcrystalline cellulose (M) as IDF, or their mixture (GM), were compared. 28611761 2 5 theme microcrystalline 495:510 arg1 M 523:523 M 523:523 M 523:523 Thus, bacterial community composition and function in the colon of BALB/c mice (n = 7) fed with a high level (approximately 20%) of typical SDF, oat-derived β-glucan (G), microcrystalline cellulose (M) as IDF, or their mixture (GM), were compared. 28611761 12 6 theme conditional 2531:2541 arg1 pathogens 2543:2551 the conditional pathogens 2527:2551 the conditional pathogens in the colon of mice 2527:2572 Co-supplementation of the two fibers may help to increase the bacterial diversity and reduce the conditional pathogens in the colon of mice. 28611761 4 7 theme bacterial 825:833 arg1 α-diversity 835:845 The bacterial α-diversity 821:845 The bacterial α-diversity of group G 821:856 The bacterial α-diversity of group G was significantly lower than other groups (p < 0.01). 28611761 4 7 theme bacterial 825:833 arg1 lower 876:880 lower 876:880 lower 876:880 The bacterial α-diversity of group G was significantly lower than other groups (p < 0.01). 28611761 5 8 theme bacteria 950:957 arg1 abundance 937:945 the relative abundance 924:945 the relative abundance of bacteria belonging to the phylum Bacteroidetes 924:995 In group G, the relative abundance of bacteria belonging to the phylum Bacteroidetes was significantly increased, whereas bacteria from the phylum Firmicutes were significantly decreased (p < 0.01). 28611761 12 9 theme fibers 2464:2469 arg1 Co-supplementation 2434:2451 Co-supplementation 2434:2451 Co-supplementation of the two fibers 2434:2469 Co-supplementation of the two fibers may help to increase the bacterial diversity and reduce the conditional pathogens in the colon of mice. 28611761 3 10 theme p 796:796 arg1 < 798:798 p < 0.05 796:803 p < 0.05 796:803 Mice in group G showed a lowest average feed intake (p < 0.05) but no change on the average body weight gain (p > 0.05) compared to other groups, which may be associated with the highest concentration of colonic propionate (p < 0.05) in these mice. 28611761 3 10 theme p 796:796 arg1 propionate 784:793 colonic propionate 776:793 colonic propionate (p < 0.05) in these mice 776:818 Mice in group G showed a lowest average feed intake (p < 0.05) but no change on the average body weight gain (p > 0.05) compared to other groups, which may be associated with the highest concentration of colonic propionate (p < 0.05) in these mice. 28611761 9 11 theme bacteria 1666:1673 arg1 abundant 1837:1844 abundant 1837:1844 abundant 1837:1844 The relative abundance of bacteria from the three classes of Proteobacteria, Betaproteobacteria, Gammaproteobacteria (including Enterobacteriaceae) and Deltaproteobacteria, were significantly more abundant in group G, indicating a higher ratio of conditional pathogenic bacteria in mice fed dietary β-glucan in current study. 28611761 9 11 theme bacteria 1666:1673 arg1 abundance 1653:1661 The relative abundance 1640:1661 The relative abundance of bacteria from the three classes of Proteobacteria, Betaproteobacteria, Gammaproteobacteria (including Enterobacteriaceae) and Deltaproteobacteria, 1640:1811 The relative abundance of bacteria from the three classes of Proteobacteria, Betaproteobacteria, Gammaproteobacteria (including Enterobacteriaceae) and Deltaproteobacteria, were significantly more abundant in group G, indicating a higher ratio of conditional pathogenic bacteria in mice fed dietary β-glucan in current study. 28611761 9 12 theme dietary 1931:1937 arg1 β-glucan 1939:1946 dietary β-glucan 1931:1946 dietary β-glucan in current study 1931:1963 The relative abundance of bacteria from the three classes of Proteobacteria, Betaproteobacteria, Gammaproteobacteria (including Enterobacteriaceae) and Deltaproteobacteria, were significantly more abundant in group G, indicating a higher ratio of conditional pathogenic bacteria in mice fed dietary β-glucan in current study. 28611761 9 13 from β-glucan 1939:1946 arg1 study 1959:1963 current study 1951:1963 current study 1951:1963 The relative abundance of bacteria from the three classes of Proteobacteria, Betaproteobacteria, Gammaproteobacteria (including Enterobacteriaceae) and Deltaproteobacteria, were significantly more abundant in group G, indicating a higher ratio of conditional pathogenic bacteria in mice fed dietary β-glucan in current study. 28611761 10 14 theme " 2079:2079 arg1 pathways 2081:2088 "Energy metabolism" and "Carbohydrate metabolism" pathways 2031:2088 "Energy metabolism" and "Carbohydrate metabolism" pathways 2031:2088 The predicted colonic microbial function showed an enrichment of "Energy metabolism" and "Carbohydrate metabolism" pathways in mice from group G and M, suggesting that the altered bacterial community in the colon of mice with the two dietary fibers probably resulted in a more efficient degradation of dietary polysaccharides. 28611761 5 15 dep increased 1015:1023 arg1 whereas 1026:1032 whereas 1026:1032 whereas 1026:1032 In group G, the relative abundance of bacteria belonging to the phylum Bacteroidetes was significantly increased, whereas bacteria from the phylum Firmicutes were significantly decreased (p < 0.01). 28611761 4 16 theme p 901:901 arg1 groups 893:898 other groups 887:898 other groups (p < 0.01) 887:909 The bacterial α-diversity of group G was significantly lower than other groups (p < 0.01). 28611761 4 16 theme p 901:901 arg1 < 903:903 p < 0.01 901:908 p < 0.01 901:908 The bacterial α-diversity of group G was significantly lower than other groups (p < 0.01). 28611761 3 17 theme average 604:610 arg1 intake 617:622 a lowest average feed intake 595:622 a lowest average feed intake (p < 0.05) 595:633 Mice in group G showed a lowest average feed intake (p < 0.05) but no change on the average body weight gain (p > 0.05) compared to other groups, which may be associated with the highest concentration of colonic propionate (p < 0.05) in these mice. 28611761 3 17 theme average 604:610 arg1 < 627:627 p < 0.05 625:632 p < 0.05 625:632 Mice in group G showed a lowest average feed intake (p < 0.05) but no change on the average body weight gain (p > 0.05) compared to other groups, which may be associated with the highest concentration of colonic propionate (p < 0.05) in these mice. 28611761 2 18 theme oat-derived 469:479 arg1 GM 552:553 GM 552:553 GM 552:553 Thus, bacterial community composition and function in the colon of BALB/c mice (n = 7) fed with a high level (approximately 20%) of typical SDF, oat-derived β-glucan (G), microcrystalline cellulose (M) as IDF, or their mixture (GM), were compared. 28611761 2 18 theme oat-derived 469:479 arg1 G 491:491 G 491:491 G 491:491 Thus, bacterial community composition and function in the colon of BALB/c mice (n = 7) fed with a high level (approximately 20%) of typical SDF, oat-derived β-glucan (G), microcrystalline cellulose (M) as IDF, or their mixture (GM), were compared. 28611761 2 18 theme oat-derived 469:479 arg1 SDF 464:466 typical SDF 456:466 typical SDF 456:466 Thus, bacterial community composition and function in the colon of BALB/c mice (n = 7) fed with a high level (approximately 20%) of typical SDF, oat-derived β-glucan (G), microcrystalline cellulose (M) as IDF, or their mixture (GM), were compared. 28611761 2 18 theme oat-derived 469:479 arg1 β-glucan 481:488 oat-derived β-glucan 469:488 oat-derived β-glucan (G) 469:492 Thus, bacterial community composition and function in the colon of BALB/c mice (n = 7) fed with a high level (approximately 20%) of typical SDF, oat-derived β-glucan (G), microcrystalline cellulose (M) as IDF, or their mixture (GM), were compared. 28611761 10 19 theme dietary 2268:2274 arg1 polysaccharides 2276:2290 dietary polysaccharides 2268:2290 dietary polysaccharides 2268:2290 The predicted colonic microbial function showed an enrichment of "Energy metabolism" and "Carbohydrate metabolism" pathways in mice from group G and M, suggesting that the altered bacterial community in the colon of mice with the two dietary fibers probably resulted in a more efficient degradation of dietary polysaccharides. 28611761 0 20 theme Communities 123:133 arg1 Composition 66:76 Composition 66:76 Composition 66:76 Different Types of Dietary Fibers Trigger Specific Alterations in Composition and Predicted Functions of Colonic Bacterial Communities in BALB/c Mice. 28611761 0 20 theme Communities 123:133 arg1 Functions 92:100 Predicted Functions 82:100 Predicted Functions of Colonic Bacterial Communities in BALB/c Mice 82:148 Different Types of Dietary Fibers Trigger Specific Alterations in Composition and Predicted Functions of Colonic Bacterial Communities in BALB/c Mice. 28611761 2 21 theme SDF 464:466 arg1 % 450:450 approximately 20% 434:450 approximately 20% 434:450 Thus, bacterial community composition and function in the colon of BALB/c mice (n = 7) fed with a high level (approximately 20%) of typical SDF, oat-derived β-glucan (G), microcrystalline cellulose (M) as IDF, or their mixture (GM), were compared. 28611761 2 21 theme SDF 464:466 arg1 level 427:431 a high level 420:431 a high level (approximately 20%) of typical SDF, oat-derived β-glucan (G), microcrystalline cellulose (M) as IDF, or their mixture (GM), 420:555 Thus, bacterial community composition and function in the colon of BALB/c mice (n = 7) fed with a high level (approximately 20%) of typical SDF, oat-derived β-glucan (G), microcrystalline cellulose (M) as IDF, or their mixture (GM), were compared. 28611761 5 22 from Firmicutes 1059:1068 arg1 bacteria 1034:1041 bacteria 1034:1041 bacteria from the phylum Firmicutes 1034:1068 In group G, the relative abundance of bacteria belonging to the phylum Bacteroidetes was significantly increased, whereas bacteria from the phylum Firmicutes were significantly decreased (p < 0.01). 28611761 9 23 theme Proteobacteria 1701:1714 arg1 classes 1690:1696 the three classes 1680:1696 the three classes of Proteobacteria 1680:1714 The relative abundance of bacteria from the three classes of Proteobacteria, Betaproteobacteria, Gammaproteobacteria (including Enterobacteriaceae) and Deltaproteobacteria, were significantly more abundant in group G, indicating a higher ratio of conditional pathogenic bacteria in mice fed dietary β-glucan in current study. 28611761 3 24 theme p 625:625 arg1 intake 617:622 a lowest average feed intake 595:622 a lowest average feed intake (p < 0.05) 595:633 Mice in group G showed a lowest average feed intake (p < 0.05) but no change on the average body weight gain (p > 0.05) compared to other groups, which may be associated with the highest concentration of colonic propionate (p < 0.05) in these mice. 28611761 3 24 theme p 625:625 arg1 < 627:627 p < 0.05 625:632 p < 0.05 625:632 Mice in group G showed a lowest average feed intake (p < 0.05) but no change on the average body weight gain (p > 0.05) compared to other groups, which may be associated with the highest concentration of colonic propionate (p < 0.05) in these mice. 28611761 8 25 from contrast 1360:1367 arg1 abundant 1438:1445 abundant 1438:1445 abundant 1438:1445 In contrast, Adlercreutzia, Odoribacter, and Coprococcus were significantly more abundant in group M, whereas Oscillospira, Desulfovibrio, and Ruminoccaceae, typical hydrogenotrophs equipped with multiple carbohydrate active enzymes, were remarkably enriched in group GM (p < 0.05). 28611761 12 26 from pathogens 2543:2551 arg1 colon 2560:2564 the colon 2556:2564 the colon of mice 2556:2572 Co-supplementation of the two fibers may help to increase the bacterial diversity and reduce the conditional pathogens in the colon of mice. 28611761 9 27 from mice 1922:1925 arg1 ratio 1878:1882 a higher ratio 1869:1882 a higher ratio of conditional pathogenic bacteria in mice fed dietary β-glucan in current study 1869:1963 The relative abundance of bacteria from the three classes of Proteobacteria, Betaproteobacteria, Gammaproteobacteria (including Enterobacteriaceae) and Deltaproteobacteria, were significantly more abundant in group G, indicating a higher ratio of conditional pathogenic bacteria in mice fed dietary β-glucan in current study. 28611761 1 28 theme insoluble 204:212 arg1 IDF 230:232 IDF 230:232 IDF 230:232 Soluble dietary fibers (SDF) are fermented more than insoluble dietary fibers (IDF), but their effect on colonic bacterial community structure and function remains unclear. 28611761 1 28 theme insoluble 204:212 arg1 fibers 222:227 insoluble dietary fibers 204:227 insoluble dietary fibers (IDF) 204:233 Soluble dietary fibers (SDF) are fermented more than insoluble dietary fibers (IDF), but their effect on colonic bacterial community structure and function remains unclear. 28611761 8 29 from enriched 1607:1614 arg1 GM 1625:1626 group GM 1619:1626 group GM (p < 0.05) 1619:1637 In contrast, Adlercreutzia, Odoribacter, and Coprococcus were significantly more abundant in group M, whereas Oscillospira, Desulfovibrio, and Ruminoccaceae, typical hydrogenotrophs equipped with multiple carbohydrate active enzymes, were remarkably enriched in group GM (p < 0.05). 28611761 8 29 from enriched 1607:1614 arg1 < 1631:1631 p < 0.05 1629:1636 p < 0.05 1629:1636 In contrast, Adlercreutzia, Odoribacter, and Coprococcus were significantly more abundant in group M, whereas Oscillospira, Desulfovibrio, and Ruminoccaceae, typical hydrogenotrophs equipped with multiple carbohydrate active enzymes, were remarkably enriched in group GM (p < 0.05). 28611761 3 30 from Mice 572:575 arg1 G 586:586 group G 580:586 group G 580:586 Mice in group G showed a lowest average feed intake (p < 0.05) but no change on the average body weight gain (p > 0.05) compared to other groups, which may be associated with the highest concentration of colonic propionate (p < 0.05) in these mice. 28611761 12 31 theme bacterial 2496:2504 arg1 diversity 2506:2514 the bacterial diversity 2492:2514 the bacterial diversity 2492:2514 Co-supplementation of the two fibers may help to increase the bacterial diversity and reduce the conditional pathogens in the colon of mice. 28611761 10 32 from community 2156:2164 arg1 colon 2173:2177 the colon 2169:2177 the colon of mice 2169:2185 The predicted colonic microbial function showed an enrichment of "Energy metabolism" and "Carbohydrate metabolism" pathways in mice from group G and M, suggesting that the altered bacterial community in the colon of mice with the two dietary fibers probably resulted in a more efficient degradation of dietary polysaccharides. 28611761 10 33 from enrichment 2017:2026 arg1 M 2115:2115 M 2115:2115 M 2115:2115 The predicted colonic microbial function showed an enrichment of "Energy metabolism" and "Carbohydrate metabolism" pathways in mice from group G and M, suggesting that the altered bacterial community in the colon of mice with the two dietary fibers probably resulted in a more efficient degradation of dietary polysaccharides. 28611761 10 33 from enrichment 2017:2026 arg1 mice 2093:2096 mice 2093:2096 mice from group G and M 2093:2115 The predicted colonic microbial function showed an enrichment of "Energy metabolism" and "Carbohydrate metabolism" pathways in mice from group G and M, suggesting that the altered bacterial community in the colon of mice with the two dietary fibers probably resulted in a more efficient degradation of dietary polysaccharides. 28611761 10 33 from enrichment 2017:2026 arg1 G 2109:2109 group G 2103:2109 group G 2103:2109 The predicted colonic microbial function showed an enrichment of "Energy metabolism" and "Carbohydrate metabolism" pathways in mice from group G and M, suggesting that the altered bacterial community in the colon of mice with the two dietary fibers probably resulted in a more efficient degradation of dietary polysaccharides. 28611761 8 34 theme carbohydrate 1562:1573 arg1 enzymes 1582:1588 multiple carbohydrate active enzymes 1553:1588 multiple carbohydrate active enzymes 1553:1588 In contrast, Adlercreutzia, Odoribacter, and Coprococcus were significantly more abundant in group M, whereas Oscillospira, Desulfovibrio, and Ruminoccaceae, typical hydrogenotrophs equipped with multiple carbohydrate active enzymes, were remarkably enriched in group GM (p < 0.05). 28611761 3 35 theme body 664:667 arg1 gain 676:679 the average body weight gain 652:679 the average body weight gain (p > 0.05) 652:690 Mice in group G showed a lowest average feed intake (p < 0.05) but no change on the average body weight gain (p > 0.05) compared to other groups, which may be associated with the highest concentration of colonic propionate (p < 0.05) in these mice. 28611761 3 35 theme body 664:667 arg1 > 684:684 p > 0.05 682:689 p > 0.05 682:689 Mice in group G showed a lowest average feed intake (p < 0.05) but no change on the average body weight gain (p > 0.05) compared to other groups, which may be associated with the highest concentration of colonic propionate (p < 0.05) in these mice. 28611761 10 36 theme bacterial 2146:2154 arg1 community 2156:2164 the altered bacterial community 2134:2164 the altered bacterial community in the colon of mice with the two dietary fibers 2134:2213 The predicted colonic microbial function showed an enrichment of "Energy metabolism" and "Carbohydrate metabolism" pathways in mice from group G and M, suggesting that the altered bacterial community in the colon of mice with the two dietary fibers probably resulted in a more efficient degradation of dietary polysaccharides. 28611761 0 37 from Functions 92:100 arg1 Mice 145:148 BALB/c Mice 138:148 BALB/c Mice 138:148 Different Types of Dietary Fibers Trigger Specific Alterations in Composition and Predicted Functions of Colonic Bacterial Communities in BALB/c Mice. 28611761 10 38 theme colonic 1980:1986 arg1 function 1998:2005 The predicted colonic microbial function 1966:2005 The predicted colonic microbial function 1966:2005 The predicted colonic microbial function showed an enrichment of "Energy metabolism" and "Carbohydrate metabolism" pathways in mice from group G and M, suggesting that the altered bacterial community in the colon of mice with the two dietary fibers probably resulted in a more efficient degradation of dietary polysaccharides. 28611761 1 39 theme Soluble 151:157 arg1 SDF 175:177 SDF 175:177 SDF 175:177 Soluble dietary fibers (SDF) are fermented more than insoluble dietary fibers (IDF), but their effect on colonic bacterial community structure and function remains unclear. 28611761 1 39 theme Soluble 151:157 arg1 fibers 167:172 Soluble dietary fibers 151:172 Soluble dietary fibers (SDF) 151:178 Soluble dietary fibers (SDF) are fermented more than insoluble dietary fibers (IDF), but their effect on colonic bacterial community structure and function remains unclear. 28611761 3 40 theme p 682:682 arg1 gain 676:679 the average body weight gain 652:679 the average body weight gain (p > 0.05) 652:690 Mice in group G showed a lowest average feed intake (p < 0.05) but no change on the average body weight gain (p > 0.05) compared to other groups, which may be associated with the highest concentration of colonic propionate (p < 0.05) in these mice. 28611761 3 40 theme p 682:682 arg1 > 684:684 p > 0.05 682:689 p > 0.05 682:689 Mice in group G showed a lowest average feed intake (p < 0.05) but no change on the average body weight gain (p > 0.05) compared to other groups, which may be associated with the highest concentration of colonic propionate (p < 0.05) in these mice. 28611761 8 41 from abundant 1438:1445 arg1 contrast 1360:1367 contrast 1360:1367 contrast 1360:1367 In contrast, Adlercreutzia, Odoribacter, and Coprococcus were significantly more abundant in group M, whereas Oscillospira, Desulfovibrio, and Ruminoccaceae, typical hydrogenotrophs equipped with multiple carbohydrate active enzymes, were remarkably enriched in group GM (p < 0.05). 28611761 8 41 from abundant 1438:1445 arg1 M 1456:1456 group M 1450:1456 group M 1450:1456 In contrast, Adlercreutzia, Odoribacter, and Coprococcus were significantly more abundant in group M, whereas Oscillospira, Desulfovibrio, and Ruminoccaceae, typical hydrogenotrophs equipped with multiple carbohydrate active enzymes, were remarkably enriched in group GM (p < 0.05). 28611761 3 42 theme other 704:708 arg1 groups 710:715 other groups 704:715 other groups 704:715 Mice in group G showed a lowest average feed intake (p < 0.05) but no change on the average body weight gain (p > 0.05) compared to other groups, which may be associated with the highest concentration of colonic propionate (p < 0.05) in these mice. 28611761 7 43 theme relative 1326:1333 arg1 abundance 1335:1343 relative abundance 1326:1343 relative abundance in group G 1326:1354 Bacteroides, Dehalobacterium, and Prevotella, including known acetogens and carbohydrate fermenting organisms, were significantly increased in relative abundance in group G. 28611761 0 44 theme Colonic 105:111 arg1 Communities 123:133 Colonic Bacterial Communities 105:133 Colonic Bacterial Communities 105:133 Different Types of Dietary Fibers Trigger Specific Alterations in Composition and Predicted Functions of Colonic Bacterial Communities in BALB/c Mice. 28611761 9 45 from bacteria 1910:1917 arg1 mice 1922:1925 mice 1922:1925 mice fed dietary β-glucan in current study 1922:1963 The relative abundance of bacteria from the three classes of Proteobacteria, Betaproteobacteria, Gammaproteobacteria (including Enterobacteriaceae) and Deltaproteobacteria, were significantly more abundant in group G, indicating a higher ratio of conditional pathogenic bacteria in mice fed dietary β-glucan in current study. 28611761 8 46 theme group 1619:1623 arg1 GM 1625:1626 group GM 1619:1626 group GM (p < 0.05) 1619:1637 In contrast, Adlercreutzia, Odoribacter, and Coprococcus were significantly more abundant in group M, whereas Oscillospira, Desulfovibrio, and Ruminoccaceae, typical hydrogenotrophs equipped with multiple carbohydrate active enzymes, were remarkably enriched in group GM (p < 0.05). 28611761 8 46 theme group 1619:1623 arg1 < 1631:1631 p < 0.05 1629:1636 p < 0.05 1629:1636 In contrast, Adlercreutzia, Odoribacter, and Coprococcus were significantly more abundant in group M, whereas Oscillospira, Desulfovibrio, and Ruminoccaceae, typical hydrogenotrophs equipped with multiple carbohydrate active enzymes, were remarkably enriched in group GM (p < 0.05). 28611761 10 47 theme Energy 2032:2037 arg1 metabolism 2039:2048 Energy metabolism 2032:2048 "Energy metabolism" 2031:2049 The predicted colonic microbial function showed an enrichment of "Energy metabolism" and "Carbohydrate metabolism" pathways in mice from group G and M, suggesting that the altered bacterial community in the colon of mice with the two dietary fibers probably resulted in a more efficient degradation of dietary polysaccharides. 28611761 5 48 theme p 1100:1100 arg1 < 1102:1102 p < 0.01 1100:1107 p < 0.01 1100:1107 In group G, the relative abundance of bacteria belonging to the phylum Bacteroidetes was significantly increased, whereas bacteria from the phylum Firmicutes were significantly decreased (p < 0.01). 28611761 0 49 theme Different 0:8 arg1 Types 10:14 Different Types 0:14 Different Types of Dietary Fibers 0:32 Different Types of Dietary Fibers Trigger Specific Alterations in Composition and Predicted Functions of Colonic Bacterial Communities in BALB/c Mice. 28611761 5 50 theme group 915:919 arg1 G 921:921 group G 915:921 group G 915:921 In group G, the relative abundance of bacteria belonging to the phylum Bacteroidetes was significantly increased, whereas bacteria from the phylum Firmicutes were significantly decreased (p < 0.01). 28611761 3 51 from propionate 784:793 arg1 mice 815:818 these mice 809:818 these mice 809:818 Mice in group G showed a lowest average feed intake (p < 0.05) but no change on the average body weight gain (p > 0.05) compared to other groups, which may be associated with the highest concentration of colonic propionate (p < 0.05) in these mice. 28611761 10 52 theme mice 2182:2185 arg1 colon 2173:2177 the colon 2169:2177 the colon of mice 2169:2185 The predicted colonic microbial function showed an enrichment of "Energy metabolism" and "Carbohydrate metabolism" pathways in mice from group G and M, suggesting that the altered bacterial community in the colon of mice with the two dietary fibers probably resulted in a more efficient degradation of dietary polysaccharides. 28611761 11 53 theme mice 2392:2395 arg1 community 2379:2387 colonic bacterial community 2361:2387 colonic bacterial community of mice 2361:2395 Our result suggests that the influence of dietary β-glucan (SDF) on colonic bacterial community of mice was more extensively than MCC (IDF). 28611761 3 54 from change 642:647 arg1 gain 676:679 the average body weight gain 652:679 the average body weight gain (p > 0.05) 652:690 Mice in group G showed a lowest average feed intake (p < 0.05) but no change on the average body weight gain (p > 0.05) compared to other groups, which may be associated with the highest concentration of colonic propionate (p < 0.05) in these mice. 28611761 3 54 from change 642:647 arg1 > 684:684 p > 0.05 682:689 p > 0.05 682:689 Mice in group G showed a lowest average feed intake (p < 0.05) but no change on the average body weight gain (p > 0.05) compared to other groups, which may be associated with the highest concentration of colonic propionate (p < 0.05) in these mice. 28611761 5 55 theme phylum 1052:1057 arg1 Firmicutes 1059:1068 the phylum Firmicutes 1048:1068 the phylum Firmicutes 1048:1068 In group G, the relative abundance of bacteria belonging to the phylum Bacteroidetes was significantly increased, whereas bacteria from the phylum Firmicutes were significantly decreased (p < 0.01). 28611761 2 56 theme mice 398:401 arg1 colon 382:386 the colon 378:386 the colon of BALB/c mice (n = 7) fed with a high level (approximately 20%) of typical SDF, oat-derived β-glucan (G), microcrystalline cellulose (M) as IDF, or their mixture (GM), 378:555 Thus, bacterial community composition and function in the colon of BALB/c mice (n = 7) fed with a high level (approximately 20%) of typical SDF, oat-derived β-glucan (G), microcrystalline cellulose (M) as IDF, or their mixture (GM), were compared. 28611761 1 57 theme colonic 256:262 arg1 structure 284:292 colonic bacterial community structure 256:292 colonic bacterial community structure 256:292 Soluble dietary fibers (SDF) are fermented more than insoluble dietary fibers (IDF), but their effect on colonic bacterial community structure and function remains unclear. 28611761 0 58 theme Fibers 27:32 arg1 Types 10:14 Different Types 0:14 Different Types of Dietary Fibers 0:32 Different Types of Dietary Fibers Trigger Specific Alterations in Composition and Predicted Functions of Colonic Bacterial Communities in BALB/c Mice. 28611761 1 59 theme community 274:282 arg1 structure 284:292 colonic bacterial community structure 256:292 colonic bacterial community structure 256:292 Soluble dietary fibers (SDF) are fermented more than insoluble dietary fibers (IDF), but their effect on colonic bacterial community structure and function remains unclear. 28611761 2 60 from function 366:373 arg1 colon 382:386 the colon 378:386 the colon of BALB/c mice (n = 7) fed with a high level (approximately 20%) of typical SDF, oat-derived β-glucan (G), microcrystalline cellulose (M) as IDF, or their mixture (GM), 378:555 Thus, bacterial community composition and function in the colon of BALB/c mice (n = 7) fed with a high level (approximately 20%) of typical SDF, oat-derived β-glucan (G), microcrystalline cellulose (M) as IDF, or their mixture (GM), were compared. 28611761 10 61 theme dietary 2200:2206 arg1 fibers 2208:2213 the two dietary fibers 2192:2213 the two dietary fibers 2192:2213 The predicted colonic microbial function showed an enrichment of "Energy metabolism" and "Carbohydrate metabolism" pathways in mice from group G and M, suggesting that the altered bacterial community in the colon of mice with the two dietary fibers probably resulted in a more efficient degradation of dietary polysaccharides. 28611761 0 62 theme Specific 42:49 arg1 Alterations 51:61 Specific Alterations 42:61 Specific Alterations in Composition and Predicted Functions of Colonic Bacterial Communities in BALB/c Mice 42:148 Different Types of Dietary Fibers Trigger Specific Alterations in Composition and Predicted Functions of Colonic Bacterial Communities in BALB/c Mice. 28611761 7 63 theme fermenting 1272:1281 arg1 organisms 1283:1291 carbohydrate fermenting organisms 1259:1291 carbohydrate fermenting organisms 1259:1291 Bacteroides, Dehalobacterium, and Prevotella, including known acetogens and carbohydrate fermenting organisms, were significantly increased in relative abundance in group G. 28611761 4 64 theme group 850:854 arg1 G 856:856 group G 850:856 group G 850:856 The bacterial α-diversity of group G was significantly lower than other groups (p < 0.01). 28611761 9 65 theme higher 1871:1876 arg1 ratio 1878:1882 a higher ratio 1869:1882 a higher ratio of conditional pathogenic bacteria in mice fed dietary β-glucan in current study 1869:1963 The relative abundance of bacteria from the three classes of Proteobacteria, Betaproteobacteria, Gammaproteobacteria (including Enterobacteriaceae) and Deltaproteobacteria, were significantly more abundant in group G, indicating a higher ratio of conditional pathogenic bacteria in mice fed dietary β-glucan in current study. 28611761 1 66 theme dietary 214:220 arg1 IDF 230:232 IDF 230:232 IDF 230:232 Soluble dietary fibers (SDF) are fermented more than insoluble dietary fibers (IDF), but their effect on colonic bacterial community structure and function remains unclear. 28611761 1 66 theme dietary 214:220 arg1 fibers 222:227 insoluble dietary fibers 204:227 insoluble dietary fibers (IDF) 204:233 Soluble dietary fibers (SDF) are fermented more than insoluble dietary fibers (IDF), but their effect on colonic bacterial community structure and function remains unclear. 28611761 3 67 theme colonic 776:782 arg1 < 798:798 p < 0.05 796:803 p < 0.05 796:803 Mice in group G showed a lowest average feed intake (p < 0.05) but no change on the average body weight gain (p > 0.05) compared to other groups, which may be associated with the highest concentration of colonic propionate (p < 0.05) in these mice. 28611761 3 67 theme colonic 776:782 arg1 propionate 784:793 colonic propionate 776:793 colonic propionate (p < 0.05) in these mice 776:818 Mice in group G showed a lowest average feed intake (p < 0.05) but no change on the average body weight gain (p > 0.05) compared to other groups, which may be associated with the highest concentration of colonic propionate (p < 0.05) in these mice. 28611761 3 68 from mice 815:818 arg1 concentration 759:771 the highest concentration 747:771 the highest concentration of colonic propionate (p < 0.05) in these mice 747:818 Mice in group G showed a lowest average feed intake (p < 0.05) but no change on the average body weight gain (p > 0.05) compared to other groups, which may be associated with the highest concentration of colonic propionate (p < 0.05) in these mice. 28611761 7 69 theme known 1239:1243 arg1 acetogens 1245:1253 known acetogens 1239:1253 known acetogens 1239:1253 Bacteroides, Dehalobacterium, and Prevotella, including known acetogens and carbohydrate fermenting organisms, were significantly increased in relative abundance in group G. 28611761 11 70 theme dietary 2335:2341 arg1 β-glucan 2343:2350 dietary β-glucan 2335:2350 dietary β-glucan (SDF) 2335:2356 Our result suggests that the influence of dietary β-glucan (SDF) on colonic bacterial community of mice was more extensively than MCC (IDF). 28611761 11 70 theme dietary 2335:2341 arg1 SDF 2353:2355 SDF 2353:2355 SDF 2353:2355 Our result suggests that the influence of dietary β-glucan (SDF) on colonic bacterial community of mice was more extensively than MCC (IDF). 28611761 6 71 theme core 1115:1118 arg1 bacteria 1120:1127 The core bacteria 1111:1127 The core bacteria for different treatments 1111:1152 The core bacteria for different treatments showed distinct differences. 28611761 2 72 theme bacterial 330:338 arg1 composition 350:360 bacterial community composition 330:360 bacterial community composition 330:360 Thus, bacterial community composition and function in the colon of BALB/c mice (n = 7) fed with a high level (approximately 20%) of typical SDF, oat-derived β-glucan (G), microcrystalline cellulose (M) as IDF, or their mixture (GM), were compared. 28611761 5 73 theme relative 928:935 arg1 abundance 937:945 the relative abundance 924:945 the relative abundance of bacteria belonging to the phylum Bacteroidetes 924:995 In group G, the relative abundance of bacteria belonging to the phylum Bacteroidetes was significantly increased, whereas bacteria from the phylum Firmicutes were significantly decreased (p < 0.01). 28611761 11 74 from influence 2322:2330 arg1 community 2379:2387 colonic bacterial community 2361:2387 colonic bacterial community of mice 2361:2395 Our result suggests that the influence of dietary β-glucan (SDF) on colonic bacterial community of mice was more extensively than MCC (IDF). 28611761 9 75 theme relative 1644:1651 arg1 abundant 1837:1844 abundant 1837:1844 abundant 1837:1844 The relative abundance of bacteria from the three classes of Proteobacteria, Betaproteobacteria, Gammaproteobacteria (including Enterobacteriaceae) and Deltaproteobacteria, were significantly more abundant in group G, indicating a higher ratio of conditional pathogenic bacteria in mice fed dietary β-glucan in current study. 28611761 9 75 theme relative 1644:1651 arg1 abundance 1653:1661 The relative abundance 1640:1661 The relative abundance of bacteria from the three classes of Proteobacteria, Betaproteobacteria, Gammaproteobacteria (including Enterobacteriaceae) and Deltaproteobacteria, 1640:1811 The relative abundance of bacteria from the three classes of Proteobacteria, Betaproteobacteria, Gammaproteobacteria (including Enterobacteriaceae) and Deltaproteobacteria, were significantly more abundant in group G, indicating a higher ratio of conditional pathogenic bacteria in mice fed dietary β-glucan in current study. 28611761 11 76 theme colonic 2361:2367 arg1 community 2379:2387 colonic bacterial community 2361:2387 colonic bacterial community of mice 2361:2395 Our result suggests that the influence of dietary β-glucan (SDF) on colonic bacterial community of mice was more extensively than MCC (IDF). 28611761 10 77 theme " 2049:2049 arg1 pathways 2081:2088 "Energy metabolism" and "Carbohydrate metabolism" pathways 2031:2088 "Energy metabolism" and "Carbohydrate metabolism" pathways 2031:2088 The predicted colonic microbial function showed an enrichment of "Energy metabolism" and "Carbohydrate metabolism" pathways in mice from group G and M, suggesting that the altered bacterial community in the colon of mice with the two dietary fibers probably resulted in a more efficient degradation of dietary polysaccharides. 28611761 9 78 from abundance 1653:1661 arg1 classes 1690:1696 the three classes 1680:1696 the three classes of Proteobacteria 1680:1714 The relative abundance of bacteria from the three classes of Proteobacteria, Betaproteobacteria, Gammaproteobacteria (including Enterobacteriaceae) and Deltaproteobacteria, were significantly more abundant in group G, indicating a higher ratio of conditional pathogenic bacteria in mice fed dietary β-glucan in current study. 28611761 6 79 theme different 1133:1141 arg1 treatments 1143:1152 different treatments 1133:1152 different treatments 1133:1152 The core bacteria for different treatments showed distinct differences. 28611761 10 80 theme pathways 2081:2088 arg1 enrichment 2017:2026 an enrichment 2014:2026 an enrichment of "Energy metabolism" and "Carbohydrate metabolism" pathways in mice from group G and M 2014:2115 The predicted colonic microbial function showed an enrichment of "Energy metabolism" and "Carbohydrate metabolism" pathways in mice from group G and M, suggesting that the altered bacterial community in the colon of mice with the two dietary fibers probably resulted in a more efficient degradation of dietary polysaccharides. 28611761 2 81 link oat-derived 469:479 arg1 GM 552:553 GM 552:553 GM 552:553 Thus, bacterial community composition and function in the colon of BALB/c mice (n = 7) fed with a high level (approximately 20%) of typical SDF, oat-derived β-glucan (G), microcrystalline cellulose (M) as IDF, or their mixture (GM), were compared. 28611761 2 81 link oat-derived 469:479 arg1 G 491:491 G 491:491 G 491:491 Thus, bacterial community composition and function in the colon of BALB/c mice (n = 7) fed with a high level (approximately 20%) of typical SDF, oat-derived β-glucan (G), microcrystalline cellulose (M) as IDF, or their mixture (GM), were compared. 28611761 2 81 link oat-derived 469:479 arg1 SDF 464:466 typical SDF 456:466 typical SDF 456:466 Thus, bacterial community composition and function in the colon of BALB/c mice (n = 7) fed with a high level (approximately 20%) of typical SDF, oat-derived β-glucan (G), microcrystalline cellulose (M) as IDF, or their mixture (GM), were compared. 28611761 2 81 link oat-derived 469:479 arg1 β-glucan 481:488 oat-derived β-glucan 469:488 oat-derived β-glucan (G) 469:492 Thus, bacterial community composition and function in the colon of BALB/c mice (n = 7) fed with a high level (approximately 20%) of typical SDF, oat-derived β-glucan (G), microcrystalline cellulose (M) as IDF, or their mixture (GM), were compared. 28611761 3 82 theme group 580:584 arg1 G 586:586 group G 580:586 group G 580:586 Mice in group G showed a lowest average feed intake (p < 0.05) but no change on the average body weight gain (p > 0.05) compared to other groups, which may be associated with the highest concentration of colonic propionate (p < 0.05) in these mice. 28611761 1 83 from effect 246:251 arg1 structure 284:292 colonic bacterial community structure 256:292 colonic bacterial community structure 256:292 Soluble dietary fibers (SDF) are fermented more than insoluble dietary fibers (IDF), but their effect on colonic bacterial community structure and function remains unclear. 28611761 1 83 from effect 246:251 arg1 function 298:305 function 298:305 function 298:305 Soluble dietary fibers (SDF) are fermented more than insoluble dietary fibers (IDF), but their effect on colonic bacterial community structure and function remains unclear. 28611761 10 84 theme metabolism 2069:2078 arg1 " 2079:2079 "Carbohydrate metabolism" 2055:2079 "Carbohydrate metabolism" 2055:2079 The predicted colonic microbial function showed an enrichment of "Energy metabolism" and "Carbohydrate metabolism" pathways in mice from group G and M, suggesting that the altered bacterial community in the colon of mice with the two dietary fibers probably resulted in a more efficient degradation of dietary polysaccharides. 28611761 2 85 from composition 350:360 arg1 colon 382:386 the colon 378:386 the colon of BALB/c mice (n = 7) fed with a high level (approximately 20%) of typical SDF, oat-derived β-glucan (G), microcrystalline cellulose (M) as IDF, or their mixture (GM), 378:555 Thus, bacterial community composition and function in the colon of BALB/c mice (n = 7) fed with a high level (approximately 20%) of typical SDF, oat-derived β-glucan (G), microcrystalline cellulose (M) as IDF, or their mixture (GM), were compared. 28611761 3 86 theme feed 612:615 arg1 intake 617:622 a lowest average feed intake 595:622 a lowest average feed intake (p < 0.05) 595:633 Mice in group G showed a lowest average feed intake (p < 0.05) but no change on the average body weight gain (p > 0.05) compared to other groups, which may be associated with the highest concentration of colonic propionate (p < 0.05) in these mice. 28611761 3 86 theme feed 612:615 arg1 < 627:627 p < 0.05 625:632 p < 0.05 625:632 Mice in group G showed a lowest average feed intake (p < 0.05) but no change on the average body weight gain (p > 0.05) compared to other groups, which may be associated with the highest concentration of colonic propionate (p < 0.05) in these mice. 28611761 10 87 theme group 2103:2107 arg1 G 2109:2109 group G 2103:2109 group G 2103:2109 The predicted colonic microbial function showed an enrichment of "Energy metabolism" and "Carbohydrate metabolism" pathways in mice from group G and M, suggesting that the altered bacterial community in the colon of mice with the two dietary fibers probably resulted in a more efficient degradation of dietary polysaccharides. 28611761 4 88 theme other 887:891 arg1 groups 893:898 other groups 887:898 other groups (p < 0.01) 887:909 The bacterial α-diversity of group G was significantly lower than other groups (p < 0.01). 28611761 4 88 theme other 887:891 arg1 < 903:903 p < 0.01 901:908 p < 0.01 901:908 The bacterial α-diversity of group G was significantly lower than other groups (p < 0.01). 28611761 3 89 theme lowest 597:602 arg1 intake 617:622 a lowest average feed intake 595:622 a lowest average feed intake (p < 0.05) 595:633 Mice in group G showed a lowest average feed intake (p < 0.05) but no change on the average body weight gain (p > 0.05) compared to other groups, which may be associated with the highest concentration of colonic propionate (p < 0.05) in these mice. 28611761 3 89 theme lowest 597:602 arg1 < 627:627 p < 0.05 625:632 p < 0.05 625:632 Mice in group G showed a lowest average feed intake (p < 0.05) but no change on the average body weight gain (p > 0.05) compared to other groups, which may be associated with the highest concentration of colonic propionate (p < 0.05) in these mice. 28611761 2 90 theme typical 456:462 arg1 cellulose 512:520 microcrystalline cellulose 495:520 microcrystalline cellulose (M) as IDF 495:531 Thus, bacterial community composition and function in the colon of BALB/c mice (n = 7) fed with a high level (approximately 20%) of typical SDF, oat-derived β-glucan (G), microcrystalline cellulose (M) as IDF, or their mixture (GM), were compared. 28611761 2 90 theme typical 456:462 arg1 mixture 543:549 their mixture 537:549 their mixture 537:549 Thus, bacterial community composition and function in the colon of BALB/c mice (n = 7) fed with a high level (approximately 20%) of typical SDF, oat-derived β-glucan (G), microcrystalline cellulose (M) as IDF, or their mixture (GM), were compared. 28611761 2 90 theme typical 456:462 arg1 SDF 464:466 typical SDF 456:466 typical SDF 456:466 Thus, bacterial community composition and function in the colon of BALB/c mice (n = 7) fed with a high level (approximately 20%) of typical SDF, oat-derived β-glucan (G), microcrystalline cellulose (M) as IDF, or their mixture (GM), were compared. 28611761 2 90 theme typical 456:462 arg1 β-glucan 481:488 oat-derived β-glucan 469:488 oat-derived β-glucan (G) 469:492 Thus, bacterial community composition and function in the colon of BALB/c mice (n = 7) fed with a high level (approximately 20%) of typical SDF, oat-derived β-glucan (G), microcrystalline cellulose (M) as IDF, or their mixture (GM), were compared. 28611761 0 91 from Composition 66:76 arg1 Mice 145:148 BALB/c Mice 138:148 BALB/c Mice 138:148 Different Types of Dietary Fibers Trigger Specific Alterations in Composition and Predicted Functions of Colonic Bacterial Communities in BALB/c Mice. 28611761 10 92 theme efficient 2243:2251 arg1 degradation 2253:2263 a more efficient degradation 2236:2263 a more efficient degradation of dietary polysaccharides 2236:2290 The predicted colonic microbial function showed an enrichment of "Energy metabolism" and "Carbohydrate metabolism" pathways in mice from group G and M, suggesting that the altered bacterial community in the colon of mice with the two dietary fibers probably resulted in a more efficient degradation of dietary polysaccharides. 28611761 9 93 theme current 1951:1957 arg1 study 1959:1963 current study 1951:1963 current study 1951:1963 The relative abundance of bacteria from the three classes of Proteobacteria, Betaproteobacteria, Gammaproteobacteria (including Enterobacteriaceae) and Deltaproteobacteria, were significantly more abundant in group G, indicating a higher ratio of conditional pathogenic bacteria in mice fed dietary β-glucan in current study. 28611761 8 94 theme typical 1515:1521 arg1 hydrogenotrophs 1523:1537 typical hydrogenotrophs 1515:1537 typical hydrogenotrophs equipped with multiple carbohydrate active enzymes 1515:1588 In contrast, Adlercreutzia, Odoribacter, and Coprococcus were significantly more abundant in group M, whereas Oscillospira, Desulfovibrio, and Ruminoccaceae, typical hydrogenotrophs equipped with multiple carbohydrate active enzymes, were remarkably enriched in group GM (p < 0.05). 28611761 8 94 theme typical 1515:1521 arg1 Oscillospira 1467:1478 Oscillospira 1467:1478 Oscillospira 1467:1478 In contrast, Adlercreutzia, Odoribacter, and Coprococcus were significantly more abundant in group M, whereas Oscillospira, Desulfovibrio, and Ruminoccaceae, typical hydrogenotrophs equipped with multiple carbohydrate active enzymes, were remarkably enriched in group GM (p < 0.05). 28611761 9 95 from classes 1690:1696 arg1 Deltaproteobacteria 1792:1810 Deltaproteobacteria 1792:1810 Deltaproteobacteria 1792:1810 The relative abundance of bacteria from the three classes of Proteobacteria, Betaproteobacteria, Gammaproteobacteria (including Enterobacteriaceae) and Deltaproteobacteria, were significantly more abundant in group G, indicating a higher ratio of conditional pathogenic bacteria in mice fed dietary β-glucan in current study. 28611761 9 95 from classes 1690:1696 arg1 Gammaproteobacteria 1737:1755 Gammaproteobacteria 1737:1755 Gammaproteobacteria 1737:1755 The relative abundance of bacteria from the three classes of Proteobacteria, Betaproteobacteria, Gammaproteobacteria (including Enterobacteriaceae) and Deltaproteobacteria, were significantly more abundant in group G, indicating a higher ratio of conditional pathogenic bacteria in mice fed dietary β-glucan in current study. 28611761 9 95 from classes 1690:1696 arg1 abundant 1837:1844 abundant 1837:1844 abundant 1837:1844 The relative abundance of bacteria from the three classes of Proteobacteria, Betaproteobacteria, Gammaproteobacteria (including Enterobacteriaceae) and Deltaproteobacteria, were significantly more abundant in group G, indicating a higher ratio of conditional pathogenic bacteria in mice fed dietary β-glucan in current study. 28611761 9 95 from classes 1690:1696 arg1 bacteria 1666:1673 bacteria 1666:1673 bacteria from the three classes of Proteobacteria 1666:1714 The relative abundance of bacteria from the three classes of Proteobacteria, Betaproteobacteria, Gammaproteobacteria (including Enterobacteriaceae) and Deltaproteobacteria, were significantly more abundant in group G, indicating a higher ratio of conditional pathogenic bacteria in mice fed dietary β-glucan in current study. 28611761 9 95 from classes 1690:1696 arg1 abundance 1653:1661 The relative abundance 1640:1661 The relative abundance of bacteria from the three classes of Proteobacteria, Betaproteobacteria, Gammaproteobacteria (including Enterobacteriaceae) and Deltaproteobacteria, 1640:1811 The relative abundance of bacteria from the three classes of Proteobacteria, Betaproteobacteria, Gammaproteobacteria (including Enterobacteriaceae) and Deltaproteobacteria, were significantly more abundant in group G, indicating a higher ratio of conditional pathogenic bacteria in mice fed dietary β-glucan in current study. 28611761 10 96 theme microbial 1988:1996 arg1 function 1998:2005 The predicted colonic microbial function 1966:2005 The predicted colonic microbial function 1966:2005 The predicted colonic microbial function showed an enrichment of "Energy metabolism" and "Carbohydrate metabolism" pathways in mice from group G and M, suggesting that the altered bacterial community in the colon of mice with the two dietary fibers probably resulted in a more efficient degradation of dietary polysaccharides. 28611761 10 97 theme polysaccharides 2276:2290 arg1 degradation 2253:2263 a more efficient degradation 2236:2263 a more efficient degradation of dietary polysaccharides 2236:2290 The predicted colonic microbial function showed an enrichment of "Energy metabolism" and "Carbohydrate metabolism" pathways in mice from group G and M, suggesting that the altered bacterial community in the colon of mice with the two dietary fibers probably resulted in a more efficient degradation of dietary polysaccharides. 28611761 9 98 from ratio 1878:1882 arg1 mice 1922:1925 mice 1922:1925 mice fed dietary β-glucan in current study 1922:1963 The relative abundance of bacteria from the three classes of Proteobacteria, Betaproteobacteria, Gammaproteobacteria (including Enterobacteriaceae) and Deltaproteobacteria, were significantly more abundant in group G, indicating a higher ratio of conditional pathogenic bacteria in mice fed dietary β-glucan in current study. 28611761 8 99 theme multiple 1553:1560 arg1 enzymes 1582:1588 multiple carbohydrate active enzymes 1553:1588 multiple carbohydrate active enzymes 1553:1588 In contrast, Adlercreutzia, Odoribacter, and Coprococcus were significantly more abundant in group M, whereas Oscillospira, Desulfovibrio, and Ruminoccaceae, typical hydrogenotrophs equipped with multiple carbohydrate active enzymes, were remarkably enriched in group GM (p < 0.05). 28611761 3 100 theme weight 669:674 arg1 gain 676:679 the average body weight gain 652:679 the average body weight gain (p > 0.05) 652:690 Mice in group G showed a lowest average feed intake (p < 0.05) but no change on the average body weight gain (p > 0.05) compared to other groups, which may be associated with the highest concentration of colonic propionate (p < 0.05) in these mice. 28611761 3 100 theme weight 669:674 arg1 > 684:684 p > 0.05 682:689 p > 0.05 682:689 Mice in group G showed a lowest average feed intake (p < 0.05) but no change on the average body weight gain (p > 0.05) compared to other groups, which may be associated with the highest concentration of colonic propionate (p < 0.05) in these mice. 28611761 7 101 theme group 1348:1352 arg1 G 1354:1354 group G 1348:1354 group G 1348:1354 Bacteroides, Dehalobacterium, and Prevotella, including known acetogens and carbohydrate fermenting organisms, were significantly increased in relative abundance in group G. 28611761 10 102 theme altered 2138:2144 arg1 community 2156:2164 the altered bacterial community 2134:2164 the altered bacterial community in the colon of mice with the two dietary fibers 2134:2213 The predicted colonic microbial function showed an enrichment of "Energy metabolism" and "Carbohydrate metabolism" pathways in mice from group G and M, suggesting that the altered bacterial community in the colon of mice with the two dietary fibers probably resulted in a more efficient degradation of dietary polysaccharides. 28611761 10 103 theme predicted 1970:1978 arg1 function 1998:2005 The predicted colonic microbial function 1966:2005 The predicted colonic microbial function 1966:2005 The predicted colonic microbial function showed an enrichment of "Energy metabolism" and "Carbohydrate metabolism" pathways in mice from group G and M, suggesting that the altered bacterial community in the colon of mice with the two dietary fibers probably resulted in a more efficient degradation of dietary polysaccharides. 28611761 8 104 from GM 1625:1626 arg1 enriched 1607:1614 enriched 1607:1614 enriched 1607:1614 In contrast, Adlercreutzia, Odoribacter, and Coprococcus were significantly more abundant in group M, whereas Oscillospira, Desulfovibrio, and Ruminoccaceae, typical hydrogenotrophs equipped with multiple carbohydrate active enzymes, were remarkably enriched in group GM (p < 0.05). 28611761 0 105 theme Predicted 82:90 arg1 Functions 92:100 Predicted Functions 82:100 Predicted Functions of Colonic Bacterial Communities in BALB/c Mice 82:148 Different Types of Dietary Fibers Trigger Specific Alterations in Composition and Predicted Functions of Colonic Bacterial Communities in BALB/c Mice. 28611761 8 106 theme active 1575:1580 arg1 enzymes 1582:1588 multiple carbohydrate active enzymes 1553:1588 multiple carbohydrate active enzymes 1553:1588 In contrast, Adlercreutzia, Odoribacter, and Coprococcus were significantly more abundant in group M, whereas Oscillospira, Desulfovibrio, and Ruminoccaceae, typical hydrogenotrophs equipped with multiple carbohydrate active enzymes, were remarkably enriched in group GM (p < 0.05). 28611761 1 107 theme dietary 159:165 arg1 SDF 175:177 SDF 175:177 SDF 175:177 Soluble dietary fibers (SDF) are fermented more than insoluble dietary fibers (IDF), but their effect on colonic bacterial community structure and function remains unclear. 28611761 1 107 theme dietary 159:165 arg1 fibers 167:172 Soluble dietary fibers 151:172 Soluble dietary fibers (SDF) 151:178 Soluble dietary fibers (SDF) are fermented more than insoluble dietary fibers (IDF), but their effect on colonic bacterial community structure and function remains unclear. 28611761 2 108 theme high 422:425 arg1 % 450:450 approximately 20% 434:450 approximately 20% 434:450 Thus, bacterial community composition and function in the colon of BALB/c mice (n = 7) fed with a high level (approximately 20%) of typical SDF, oat-derived β-glucan (G), microcrystalline cellulose (M) as IDF, or their mixture (GM), were compared. 28611761 2 108 theme high 422:425 arg1 level 427:431 a high level 420:431 a high level (approximately 20%) of typical SDF, oat-derived β-glucan (G), microcrystalline cellulose (M) as IDF, or their mixture (GM), 420:555 Thus, bacterial community composition and function in the colon of BALB/c mice (n = 7) fed with a high level (approximately 20%) of typical SDF, oat-derived β-glucan (G), microcrystalline cellulose (M) as IDF, or their mixture (GM), were compared. 28611761 3 109 theme average 656:662 arg1 gain 676:679 the average body weight gain 652:679 the average body weight gain (p > 0.05) 652:690 Mice in group G showed a lowest average feed intake (p < 0.05) but no change on the average body weight gain (p > 0.05) compared to other groups, which may be associated with the highest concentration of colonic propionate (p < 0.05) in these mice. 28611761 3 109 theme average 656:662 arg1 > 684:684 p > 0.05 682:689 p > 0.05 682:689 Mice in group G showed a lowest average feed intake (p < 0.05) but no change on the average body weight gain (p > 0.05) compared to other groups, which may be associated with the highest concentration of colonic propionate (p < 0.05) in these mice. 28611761 0 110 from Alterations 51:61 arg1 Composition 66:76 Composition 66:76 Composition 66:76 Different Types of Dietary Fibers Trigger Specific Alterations in Composition and Predicted Functions of Colonic Bacterial Communities in BALB/c Mice. 28611761 0 110 from Alterations 51:61 arg1 Functions 92:100 Predicted Functions 82:100 Predicted Functions of Colonic Bacterial Communities in BALB/c Mice 82:148 Different Types of Dietary Fibers Trigger Specific Alterations in Composition and Predicted Functions of Colonic Bacterial Communities in BALB/c Mice. 28611761 0 111 theme Bacterial 113:121 arg1 Communities 123:133 Colonic Bacterial Communities 105:133 Colonic Bacterial Communities 105:133 Different Types of Dietary Fibers Trigger Specific Alterations in Composition and Predicted Functions of Colonic Bacterial Communities in BALB/c Mice. 28611761 3 112 from concentration 759:771 arg1 mice 815:818 these mice 809:818 these mice 809:818 Mice in group G showed a lowest average feed intake (p < 0.05) but no change on the average body weight gain (p > 0.05) compared to other groups, which may be associated with the highest concentration of colonic propionate (p < 0.05) in these mice. 28611761 12 113 theme mice 2569:2572 arg1 colon 2560:2564 the colon 2556:2564 the colon of mice 2556:2572 Co-supplementation of the two fibers may help to increase the bacterial diversity and reduce the conditional pathogens in the colon of mice. 28611761 10 114 theme metabolism 2039:2048 arg1 " 2049:2049 "Energy metabolism" 2031:2049 "Energy metabolism" 2031:2049 The predicted colonic microbial function showed an enrichment of "Energy metabolism" and "Carbohydrate metabolism" pathways in mice from group G and M, suggesting that the altered bacterial community in the colon of mice with the two dietary fibers probably resulted in a more efficient degradation of dietary polysaccharides. 28611761 10 115 with community 2156:2164 arg1 fibers 2208:2213 the two dietary fibers 2192:2213 the two dietary fibers 2192:2213 The predicted colonic microbial function showed an enrichment of "Energy metabolism" and "Carbohydrate metabolism" pathways in mice from group G and M, suggesting that the altered bacterial community in the colon of mice with the two dietary fibers probably resulted in a more efficient degradation of dietary polysaccharides. 28611761 2 116 theme = 406:406 arg1 n 404:404 n = 7 404:408 n = 7 404:408 Thus, bacterial community composition and function in the colon of BALB/c mice (n = 7) fed with a high level (approximately 20%) of typical SDF, oat-derived β-glucan (G), microcrystalline cellulose (M) as IDF, or their mixture (GM), were compared. 28611761 2 116 theme = 406:406 arg1 mice 398:401 BALB/c mice 391:401 BALB/c mice (n = 7) fed with a high level (approximately 20%) of typical SDF, oat-derived β-glucan (G), microcrystalline cellulose (M) as IDF, or their mixture (GM), 391:555 Thus, bacterial community composition and function in the colon of BALB/c mice (n = 7) fed with a high level (approximately 20%) of typical SDF, oat-derived β-glucan (G), microcrystalline cellulose (M) as IDF, or their mixture (GM), were compared. 28611761 8 117 from M 1456:1456 arg1 abundant 1438:1445 abundant 1438:1445 abundant 1438:1445 In contrast, Adlercreutzia, Odoribacter, and Coprococcus were significantly more abundant in group M, whereas Oscillospira, Desulfovibrio, and Ruminoccaceae, typical hydrogenotrophs equipped with multiple carbohydrate active enzymes, were remarkably enriched in group GM (p < 0.05). 28611761 0 118 theme Dietary 19:25 arg1 Fibers 27:32 Dietary Fibers 19:32 Dietary Fibers 19:32 Different Types of Dietary Fibers Trigger Specific Alterations in Composition and Predicted Functions of Colonic Bacterial Communities in BALB/c Mice. 28611761 11 119 theme bacterial 2369:2377 arg1 community 2379:2387 colonic bacterial community 2361:2387 colonic bacterial community of mice 2361:2395 Our result suggests that the influence of dietary β-glucan (SDF) on colonic bacterial community of mice was more extensively than MCC (IDF). 28611761 9 120 theme group 1849:1853 arg1 G 1855:1855 group G 1849:1855 group G 1849:1855 The relative abundance of bacteria from the three classes of Proteobacteria, Betaproteobacteria, Gammaproteobacteria (including Enterobacteriaceae) and Deltaproteobacteria, were significantly more abundant in group G, indicating a higher ratio of conditional pathogenic bacteria in mice fed dietary β-glucan in current study. 28611761 2 121 theme BALB/c 391:396 arg1 n 404:404 n = 7 404:408 n = 7 404:408 Thus, bacterial community composition and function in the colon of BALB/c mice (n = 7) fed with a high level (approximately 20%) of typical SDF, oat-derived β-glucan (G), microcrystalline cellulose (M) as IDF, or their mixture (GM), were compared. 28611761 2 121 theme BALB/c 391:396 arg1 mice 398:401 BALB/c mice 391:401 BALB/c mice (n = 7) fed with a high level (approximately 20%) of typical SDF, oat-derived β-glucan (G), microcrystalline cellulose (M) as IDF, or their mixture (GM), 391:555 Thus, bacterial community composition and function in the colon of BALB/c mice (n = 7) fed with a high level (approximately 20%) of typical SDF, oat-derived β-glucan (G), microcrystalline cellulose (M) as IDF, or their mixture (GM), were compared. 28611761 6 122 theme distinct 1161:1168 arg1 differences 1170:1180 distinct differences 1161:1180 distinct differences 1161:1180 The core bacteria for different treatments showed distinct differences. 28611761 1 123 theme bacterial 264:272 arg1 structure 284:292 colonic bacterial community structure 256:292 colonic bacterial community structure 256:292 Soluble dietary fibers (SDF) are fermented more than insoluble dietary fibers (IDF), but their effect on colonic bacterial community structure and function remains unclear. 28611761 7 124 from abundance 1335:1343 arg1 G 1354:1354 group G 1348:1354 group G 1348:1354 Bacteroides, Dehalobacterium, and Prevotella, including known acetogens and carbohydrate fermenting organisms, were significantly increased in relative abundance in group G. 28611761 9 125 from G 1855:1855 arg1 abundant 1837:1844 abundant 1837:1844 abundant 1837:1844 The relative abundance of bacteria from the three classes of Proteobacteria, Betaproteobacteria, Gammaproteobacteria (including Enterobacteriaceae) and Deltaproteobacteria, were significantly more abundant in group G, indicating a higher ratio of conditional pathogenic bacteria in mice fed dietary β-glucan in current study. 28611761 9 125 from G 1855:1855 arg1 abundance 1653:1661 The relative abundance 1640:1661 The relative abundance of bacteria from the three classes of Proteobacteria, Betaproteobacteria, Gammaproteobacteria (including Enterobacteriaceae) and Deltaproteobacteria, 1640:1811 The relative abundance of bacteria from the three classes of Proteobacteria, Betaproteobacteria, Gammaproteobacteria (including Enterobacteriaceae) and Deltaproteobacteria, were significantly more abundant in group G, indicating a higher ratio of conditional pathogenic bacteria in mice fed dietary β-glucan in current study. 28611761 3 126 theme highest 751:757 arg1 concentration 759:771 the highest concentration 747:771 the highest concentration of colonic propionate (p < 0.05) in these mice 747:818 Mice in group G showed a lowest average feed intake (p < 0.05) but no change on the average body weight gain (p > 0.05) compared to other groups, which may be associated with the highest concentration of colonic propionate (p < 0.05) in these mice. 28611761 9 127 from abundant 1837:1844 arg1 G 1855:1855 group G 1849:1855 group G 1849:1855 The relative abundance of bacteria from the three classes of Proteobacteria, Betaproteobacteria, Gammaproteobacteria (including Enterobacteriaceae) and Deltaproteobacteria, were significantly more abundant in group G, indicating a higher ratio of conditional pathogenic bacteria in mice fed dietary β-glucan in current study. 28611761 0 128 theme BALB/c 138:143 arg1 Mice 145:148 BALB/c Mice 138:148 BALB/c Mice 138:148 Different Types of Dietary Fibers Trigger Specific Alterations in Composition and Predicted Functions of Colonic Bacterial Communities in BALB/c Mice. 28611761 3 129 dep showed 588:593 arg1 compared 692:699 compared 692:699 showed a lowest average feed intake (p < 0.05) but no change on the average body weight gain (p > 0.05) compared to other groups, which may be associated with the highest concentration of colonic propionate (p < 0.05) in these mice 588:818 Mice in group G showed a lowest average feed intake (p < 0.05) but no change on the average body weight gain (p > 0.05) compared to other groups, which may be associated with the highest concentration of colonic propionate (p < 0.05) in these mice. 28611761 5 130 dep decreased 1089:1097 arg1 < 1102:1102 p < 0.01 1100:1107 p < 0.01 1100:1107 In group G, the relative abundance of bacteria belonging to the phylum Bacteroidetes was significantly increased, whereas bacteria from the phylum Firmicutes were significantly decreased (p < 0.01). 28611761 11 131 theme β-glucan 2343:2350 arg1 influence 2322:2330 the influence 2318:2330 the influence of dietary β-glucan (SDF) on colonic bacterial community of mice 2318:2395 Our result suggests that the influence of dietary β-glucan (SDF) on colonic bacterial community of mice was more extensively than MCC (IDF). 28611761 7 132 theme carbohydrate 1259:1270 arg1 organisms 1283:1291 carbohydrate fermenting organisms 1259:1291 carbohydrate fermenting organisms 1259:1291 Bacteroides, Dehalobacterium, and Prevotella, including known acetogens and carbohydrate fermenting organisms, were significantly increased in relative abundance in group G. 28611761 3 133 theme propionate 784:793 arg1 concentration 759:771 the highest concentration 747:771 the highest concentration of colonic propionate (p < 0.05) in these mice 747:818 Mice in group G showed a lowest average feed intake (p < 0.05) but no change on the average body weight gain (p > 0.05) compared to other groups, which may be associated with the highest concentration of colonic propionate (p < 0.05) in these mice. 28611761 4 134 theme G 856:856 arg1 α-diversity 835:845 The bacterial α-diversity 821:845 The bacterial α-diversity of group G 821:856 The bacterial α-diversity of group G was significantly lower than other groups (p < 0.01). 28611761 4 134 theme G 856:856 arg1 lower 876:880 lower 876:880 lower 876:880 The bacterial α-diversity of group G was significantly lower than other groups (p < 0.01). 28611761 10 135 from G 2109:2109 arg1 mice 2093:2096 mice 2093:2096 mice from group G and M 2093:2115 The predicted colonic microbial function showed an enrichment of "Energy metabolism" and "Carbohydrate metabolism" pathways in mice from group G and M, suggesting that the altered bacterial community in the colon of mice with the two dietary fibers probably resulted in a more efficient degradation of dietary polysaccharides. 28611761 10 135 from G 2109:2109 arg1 enrichment 2017:2026 an enrichment 2014:2026 an enrichment of "Energy metabolism" and "Carbohydrate metabolism" pathways in mice from group G and M 2014:2115 The predicted colonic microbial function showed an enrichment of "Energy metabolism" and "Carbohydrate metabolism" pathways in mice from group G and M, suggesting that the altered bacterial community in the colon of mice with the two dietary fibers probably resulted in a more efficient degradation of dietary polysaccharides. 28611761 9 136 theme conditional 1887:1897 arg1 bacteria 1910:1917 conditional pathogenic bacteria 1887:1917 conditional pathogenic bacteria in mice fed dietary β-glucan in current study 1887:1963 The relative abundance of bacteria from the three classes of Proteobacteria, Betaproteobacteria, Gammaproteobacteria (including Enterobacteriaceae) and Deltaproteobacteria, were significantly more abundant in group G, indicating a higher ratio of conditional pathogenic bacteria in mice fed dietary β-glucan in current study. 28611761 2 137 theme community 340:348 arg1 composition 350:360 bacterial community composition 330:360 bacterial community composition 330:360 Thus, bacterial community composition and function in the colon of BALB/c mice (n = 7) fed with a high level (approximately 20%) of typical SDF, oat-derived β-glucan (G), microcrystalline cellulose (M) as IDF, or their mixture (GM), were compared. 28611761 8 138 theme group 1450:1454 arg1 M 1456:1456 group M 1450:1456 group M 1450:1456 In contrast, Adlercreutzia, Odoribacter, and Coprococcus were significantly more abundant in group M, whereas Oscillospira, Desulfovibrio, and Ruminoccaceae, typical hydrogenotrophs equipped with multiple carbohydrate active enzymes, were remarkably enriched in group GM (p < 0.05). 28611761 5 139 theme phylum 976:981 arg1 Bacteroidetes 983:995 the phylum Bacteroidetes 972:995 the phylum Bacteroidetes 972:995 In group G, the relative abundance of bacteria belonging to the phylum Bacteroidetes was significantly increased, whereas bacteria from the phylum Firmicutes were significantly decreased (p < 0.01). 24622847 12 0 theme further 2174:2180 arg1 applications 2182:2193 further applications 2174:2193 further applications 2174:2193 The wide and accurate investigation of the different aspects related to the whole process represents a relevant point of novelty in this research field and suggests the operational conditions for the start-up of an open pond system for wastewater treatment and biomass production for further applications. 24622847 3 1 theme different 706:714 arg1 rate 725:728 the different dilution rate 702:728 the different dilution rate 702:728 Semi-continuous cultures were operated for 7 day at 5-, 3- and 1.5-day HRT and the different dilution rate showed a greater influence on the biomass composition and nutrient removal efficiency. 24622847 1 2 theme physiological 274:286 arg1 responses 288:296 the physiological responses 270:296 the physiological responses in terms of growth, biochemical composition and photosynthetic activity of the autochthonous freshwater algal strain Desmodesmus communis 270:434 The objective of the present study was to evaluate the nutrient removal efficiency and the physiological responses in terms of growth, biochemical composition and photosynthetic activity of the autochthonous freshwater algal strain Desmodesmus communis. 24622847 7 3 theme RLC 1374:1376 arg1 measurements 1379:1390 the rapid light curves (RLC) measurements 1350:1390 the rapid light curves (RLC) measurements 1350:1390 Moreover the accumulation of N-NH3 occurring at 1.5-day HRT caused the decrease of the photosynthetic response in terms of efficiency of light capture (α) and relative electron transport rate (rETR), both parameters extracted from the rapid light curves (RLC) measurements. 24622847 12 4 theme aspects 1943:1949 arg1 investigation 1912:1924 The wide and accurate investigation 1890:1924 The wide and accurate investigation of the different aspects related to the whole process 1890:1978 The wide and accurate investigation of the different aspects related to the whole process represents a relevant point of novelty in this research field and suggests the operational conditions for the start-up of an open pond system for wastewater treatment and biomass production for further applications. 24622847 7 5 theme curves 1366:1371 arg1 measurements 1379:1390 the rapid light curves (RLC) measurements 1350:1390 the rapid light curves (RLC) measurements 1350:1390 Moreover the accumulation of N-NH3 occurring at 1.5-day HRT caused the decrease of the photosynthetic response in terms of efficiency of light capture (α) and relative electron transport rate (rETR), both parameters extracted from the rapid light curves (RLC) measurements. 24622847 4 6 theme highest 866:872 arg1 accumulation 874:885 the highest accumulation 862:885 the highest accumulation of polysaccharides (57.2 wt 862:913 Removal of N-NH3 and P-PO4 was over 99 % and the highest accumulation of polysaccharides (57.2 wt. 24622847 6 7 theme removal 1097:1103 arg1 terms 1080:1084 terms 1080:1084 terms of ammonia removal 1080:1103 %) was achieved at 1.5-day HRT, even if, under this condition, a clear inefficiency in terms of ammonia removal was observed. 24622847 3 8 theme composition 772:782 arg1 efficiency 805:814 the biomass composition and nutrient removal efficiency 760:814 the biomass composition and nutrient removal efficiency 760:814 Semi-continuous cultures were operated for 7 day at 5-, 3- and 1.5-day HRT and the different dilution rate showed a greater influence on the biomass composition and nutrient removal efficiency. 24622847 11 9 theme strain 1852:1857 arg1 ability 1830:1836 the ability 1826:1836 the ability of this algal strain 1826:1857 % and a great increment in terms of biomass (1.64 ± 0.02 g L(-1)) due to the ability of this algal strain to accumulate intracellular N. 24622847 2 10 theme primary 579:585 arg1 effluents 612:620 both primary and secondary wastewater effluents 574:620 both primary and secondary wastewater effluents 574:620 Microalgae were grown in a primary municipal effluent under different hydraulic retention times (HRTs) and in a two-phases process using both primary and secondary wastewater effluents. 24622847 10 11 theme secondary 1650:1658 arg1 effluent 1671:1678 the secondary wastewater effluent 1646:1678 the secondary wastewater effluent 1646:1678 On the other hand, in the two-phases process, when a nutrient deprivation condition was induced by diluting the culture with the secondary wastewater effluent, the algal cells accumulated TFAs, achieving a maximum content of 9.7 wt. 24622847 1 12 theme strain 408:413 arg1 activity 361:368 photosynthetic activity 346:368 photosynthetic activity 346:368 The objective of the present study was to evaluate the nutrient removal efficiency and the physiological responses in terms of growth, biochemical composition and photosynthetic activity of the autochthonous freshwater algal strain Desmodesmus communis. 24622847 1 12 theme strain 408:413 arg1 growth 310:315 growth 310:315 growth 310:315 The objective of the present study was to evaluate the nutrient removal efficiency and the physiological responses in terms of growth, biochemical composition and photosynthetic activity of the autochthonous freshwater algal strain Desmodesmus communis. 24622847 1 12 theme strain 408:413 arg1 composition 330:340 biochemical composition 318:340 biochemical composition 318:340 The objective of the present study was to evaluate the nutrient removal efficiency and the physiological responses in terms of growth, biochemical composition and photosynthetic activity of the autochthonous freshwater algal strain Desmodesmus communis. 24622847 1 13 theme study 212:216 arg1 objective 187:195 The objective 183:195 The objective of the present study 183:216 The objective of the present study was to evaluate the nutrient removal efficiency and the physiological responses in terms of growth, biochemical composition and photosynthetic activity of the autochthonous freshwater algal strain Desmodesmus communis. 24622847 12 14 theme biomass 2151:2157 arg1 production 2159:2168 biomass production 2151:2168 biomass production 2151:2168 The wide and accurate investigation of the different aspects related to the whole process represents a relevant point of novelty in this research field and suggests the operational conditions for the start-up of an open pond system for wastewater treatment and biomass production for further applications. 24622847 7 15 theme transport 1296:1304 arg1 rate 1306:1309 relative electron transport rate 1278:1309 relative electron transport rate (rETR) 1278:1316 Moreover the accumulation of N-NH3 occurring at 1.5-day HRT caused the decrease of the photosynthetic response in terms of efficiency of light capture (α) and relative electron transport rate (rETR), both parameters extracted from the rapid light curves (RLC) measurements. 24622847 7 15 theme transport 1296:1304 arg1 rETR 1312:1315 rETR 1312:1315 rETR 1312:1315 Moreover the accumulation of N-NH3 occurring at 1.5-day HRT caused the decrease of the photosynthetic response in terms of efficiency of light capture (α) and relative electron transport rate (rETR), both parameters extracted from the rapid light curves (RLC) measurements. 24622847 11 16 from increment 1767:1775 arg1 terms 1780:1784 terms 1780:1784 terms of biomass 1780:1795 % and a great increment in terms of biomass (1.64 ± 0.02 g L(-1)) due to the ability of this algal strain to accumulate intracellular N. 24622847 3 17 theme nutrient 788:795 arg1 removal 797:803 nutrient removal 788:803 nutrient removal 788:803 Semi-continuous cultures were operated for 7 day at 5-, 3- and 1.5-day HRT and the different dilution rate showed a greater influence on the biomass composition and nutrient removal efficiency. 24622847 0 18 theme urban 155:159 arg1 effluents 172:180 urban wastewater effluents 155:180 urban wastewater effluents 155:180 Nutrient removal efficiency and physiological responses of Desmodesmus communis at different HRTs and nutrient stress condition using different sources of urban wastewater effluents. 24622847 3 19 theme Semi-continuous 623:637 arg1 cultures 639:646 Semi-continuous cultures 623:646 Semi-continuous cultures 623:646 Semi-continuous cultures were operated for 7 day at 5-, 3- and 1.5-day HRT and the different dilution rate showed a greater influence on the biomass composition and nutrient removal efficiency. 24622847 2 20 theme secondary 591:599 arg1 effluents 612:620 both primary and secondary wastewater effluents 574:620 both primary and secondary wastewater effluents 574:620 Microalgae were grown in a primary municipal effluent under different hydraulic retention times (HRTs) and in a two-phases process using both primary and secondary wastewater effluents. 24622847 12 21 theme pond 2110:2113 arg1 system 2115:2120 an open pond system 2102:2120 an open pond system for wastewater treatment and biomass production for further applications 2102:2193 The wide and accurate investigation of the different aspects related to the whole process represents a relevant point of novelty in this research field and suggests the operational conditions for the start-up of an open pond system for wastewater treatment and biomass production for further applications. 24622847 7 22 theme relative 1278:1285 arg1 rate 1306:1309 relative electron transport rate 1278:1309 relative electron transport rate (rETR) 1278:1316 Moreover the accumulation of N-NH3 occurring at 1.5-day HRT caused the decrease of the photosynthetic response in terms of efficiency of light capture (α) and relative electron transport rate (rETR), both parameters extracted from the rapid light curves (RLC) measurements. 24622847 7 22 theme relative 1278:1285 arg1 rETR 1312:1315 rETR 1312:1315 rETR 1312:1315 Moreover the accumulation of N-NH3 occurring at 1.5-day HRT caused the decrease of the photosynthetic response in terms of efficiency of light capture (α) and relative electron transport rate (rETR), both parameters extracted from the rapid light curves (RLC) measurements. 24622847 0 23 theme effluents 172:180 arg1 sources 144:150 different sources 134:150 different sources of urban wastewater effluents 134:180 Nutrient removal efficiency and physiological responses of Desmodesmus communis at different HRTs and nutrient stress condition using different sources of urban wastewater effluents. 24622847 5 24 theme high 934:937 arg1 5 day 944:948 5 day 944:948 5 day 944:948 %) was obtained at high HRT (5 day); the maximum content of proteins (26.9 wt. 24622847 5 24 theme high 934:937 arg1 HRT 939:941 high HRT 934:941 high HRT (5 day) 934:949 %) was obtained at high HRT (5 day); the maximum content of proteins (26.9 wt. 24622847 11 25 from % 1753:1753 arg1 terms 1780:1784 terms 1780:1784 terms of biomass 1780:1795 % and a great increment in terms of biomass (1.64 ± 0.02 g L(-1)) due to the ability of this algal strain to accumulate intracellular N. 24622847 0 26 theme communis 71:78 arg1 efficiency 17:26 Nutrient removal efficiency 0:26 Nutrient removal efficiency 0:26 Nutrient removal efficiency and physiological responses of Desmodesmus communis at different HRTs and nutrient stress condition using different sources of urban wastewater effluents. 24622847 0 26 theme communis 71:78 arg1 responses 46:54 physiological responses 32:54 physiological responses 32:54 Nutrient removal efficiency and physiological responses of Desmodesmus communis at different HRTs and nutrient stress condition using different sources of urban wastewater effluents. 24622847 8 27 theme significant 1396:1406 arg1 differences 1408:1418 No significant differences 1393:1418 No significant differences 1393:1418 No significant differences were observed for the total fatty acids (TFAs), with a content of 2-3.5 wt. 24622847 0 28 theme different 83:91 arg1 HRTs 93:96 different HRTs 83:96 different HRTs 83:96 Nutrient removal efficiency and physiological responses of Desmodesmus communis at different HRTs and nutrient stress condition using different sources of urban wastewater effluents. 24622847 1 29 theme activity 361:368 arg1 terms 301:305 terms 301:305 terms of growth, biochemical composition and photosynthetic activity of the autochthonous freshwater algal strain Desmodesmus communis 301:434 The objective of the present study was to evaluate the nutrient removal efficiency and the physiological responses in terms of growth, biochemical composition and photosynthetic activity of the autochthonous freshwater algal strain Desmodesmus communis. 24622847 2 30 theme two-phases 549:558 arg1 process 560:566 a two-phases process 547:566 a two-phases process using both primary and secondary wastewater effluents 547:620 Microalgae were grown in a primary municipal effluent under different hydraulic retention times (HRTs) and in a two-phases process using both primary and secondary wastewater effluents. 24622847 7 31 theme N-NH3 1148:1152 arg1 accumulation 1132:1143 the accumulation 1128:1143 the accumulation of N-NH3 occurring at 1.5-day HRT 1128:1177 Moreover the accumulation of N-NH3 occurring at 1.5-day HRT caused the decrease of the photosynthetic response in terms of efficiency of light capture (α) and relative electron transport rate (rETR), both parameters extracted from the rapid light curves (RLC) measurements. 24622847 12 32 theme operational 2059:2069 arg1 conditions 2071:2080 the operational conditions 2055:2080 the operational conditions for the start-up of an open pond system for wastewater treatment and biomass production for further applications 2055:2193 The wide and accurate investigation of the different aspects related to the whole process represents a relevant point of novelty in this research field and suggests the operational conditions for the start-up of an open pond system for wastewater treatment and biomass production for further applications. 24622847 10 33 theme other 1528:1532 arg1 hand 1534:1537 the other hand 1524:1537 the other hand 1524:1537 On the other hand, in the two-phases process, when a nutrient deprivation condition was induced by diluting the culture with the secondary wastewater effluent, the algal cells accumulated TFAs, achieving a maximum content of 9.7 wt. 24622847 0 34 theme stress 111:116 arg1 condition 118:126 nutrient stress condition 102:126 nutrient stress condition 102:126 Nutrient removal efficiency and physiological responses of Desmodesmus communis at different HRTs and nutrient stress condition using different sources of urban wastewater effluents. 24622847 1 35 theme freshwater 391:400 arg1 strain 408:413 the autochthonous freshwater algal strain 373:413 the autochthonous freshwater algal strain 373:413 The objective of the present study was to evaluate the nutrient removal efficiency and the physiological responses in terms of growth, biochemical composition and photosynthetic activity of the autochthonous freshwater algal strain Desmodesmus communis. 24622847 8 36 theme total 1442:1446 arg1 TFAs 1461:1464 TFAs 1461:1464 TFAs 1461:1464 No significant differences were observed for the total fatty acids (TFAs), with a content of 2-3.5 wt. 24622847 8 36 theme total 1442:1446 arg1 acids 1454:1458 the total fatty acids 1438:1458 the total fatty acids (TFAs) 1438:1465 No significant differences were observed for the total fatty acids (TFAs), with a content of 2-3.5 wt. 24622847 0 37 theme Nutrient 0:7 arg1 efficiency 17:26 Nutrient removal efficiency 0:26 Nutrient removal efficiency 0:26 Nutrient removal efficiency and physiological responses of Desmodesmus communis at different HRTs and nutrient stress condition using different sources of urban wastewater effluents. 24622847 7 38 theme capture 1262:1268 arg1 efficiency 1242:1251 efficiency 1242:1251 efficiency of light capture (α) and relative electron transport rate (rETR) 1242:1316 Moreover the accumulation of N-NH3 occurring at 1.5-day HRT caused the decrease of the photosynthetic response in terms of efficiency of light capture (α) and relative electron transport rate (rETR), both parameters extracted from the rapid light curves (RLC) measurements. 24622847 2 39 theme primary 464:470 arg1 effluent 482:489 a primary municipal effluent 462:489 a primary municipal effluent 462:489 Microalgae were grown in a primary municipal effluent under different hydraulic retention times (HRTs) and in a two-phases process using both primary and secondary wastewater effluents. 24622847 11 40 theme biomass 1789:1795 arg1 terms 1780:1784 terms 1780:1784 terms of biomass 1780:1795 % and a great increment in terms of biomass (1.64 ± 0.02 g L(-1)) due to the ability of this algal strain to accumulate intracellular N. 24622847 12 41 theme research 2027:2034 arg1 field 2036:2040 this research field 2022:2040 this research field 2022:2040 The wide and accurate investigation of the different aspects related to the whole process represents a relevant point of novelty in this research field and suggests the operational conditions for the start-up of an open pond system for wastewater treatment and biomass production for further applications. 24622847 6 42 theme 1.5-day 1012:1018 arg1 HRT 1020:1022 1.5-day HRT 1012:1022 1.5-day HRT 1012:1022 %) was achieved at 1.5-day HRT, even if, under this condition, a clear inefficiency in terms of ammonia removal was observed. 24622847 2 43 theme retention 517:525 arg1 HRTs 534:537 HRTs 534:537 HRTs 534:537 Microalgae were grown in a primary municipal effluent under different hydraulic retention times (HRTs) and in a two-phases process using both primary and secondary wastewater effluents. 24622847 2 43 theme retention 517:525 arg1 times 527:531 different hydraulic retention times 497:531 different hydraulic retention times (HRTs) 497:538 Microalgae were grown in a primary municipal effluent under different hydraulic retention times (HRTs) and in a two-phases process using both primary and secondary wastewater effluents. 24622847 12 44 theme relevant 1993:2000 arg1 point 2002:2006 a relevant point 1991:2006 a relevant point of novelty in this research field 1991:2040 The wide and accurate investigation of the different aspects related to the whole process represents a relevant point of novelty in this research field and suggests the operational conditions for the start-up of an open pond system for wastewater treatment and biomass production for further applications. 24622847 11 45 theme great 1761:1765 arg1 increment 1767:1775 a great increment 1759:1775 a great increment in terms of biomass (1.64 ± 0.02 g L(-1)) due to the ability of this algal strain 1759:1857 % and a great increment in terms of biomass (1.64 ± 0.02 g L(-1)) due to the ability of this algal strain to accumulate intracellular N. 24622847 0 46 theme physiological 32:44 arg1 responses 46:54 physiological responses 32:54 physiological responses 32:54 Nutrient removal efficiency and physiological responses of Desmodesmus communis at different HRTs and nutrient stress condition using different sources of urban wastewater effluents. 24622847 1 47 theme growth 310:315 arg1 terms 301:305 terms 301:305 terms of growth, biochemical composition and photosynthetic activity of the autochthonous freshwater algal strain Desmodesmus communis 301:434 The objective of the present study was to evaluate the nutrient removal efficiency and the physiological responses in terms of growth, biochemical composition and photosynthetic activity of the autochthonous freshwater algal strain Desmodesmus communis. 24622847 4 48 dep polysaccharides 890:904 arg1 57.2 wt 907:913 57.2 wt 907:913 57.2 wt 907:913 Removal of N-NH3 and P-PO4 was over 99 % and the highest accumulation of polysaccharides (57.2 wt. 24622847 2 49 theme different 497:505 arg1 HRTs 534:537 HRTs 534:537 HRTs 534:537 Microalgae were grown in a primary municipal effluent under different hydraulic retention times (HRTs) and in a two-phases process using both primary and secondary wastewater effluents. 24622847 2 49 theme different 497:505 arg1 times 527:531 different hydraulic retention times 497:531 different hydraulic retention times (HRTs) 497:538 Microalgae were grown in a primary municipal effluent under different hydraulic retention times (HRTs) and in a two-phases process using both primary and secondary wastewater effluents. 24622847 1 50 theme biochemical 318:328 arg1 composition 330:340 biochemical composition 318:340 biochemical composition 318:340 The objective of the present study was to evaluate the nutrient removal efficiency and the physiological responses in terms of growth, biochemical composition and photosynthetic activity of the autochthonous freshwater algal strain Desmodesmus communis. 24622847 12 51 theme whole 1966:1970 arg1 process 1972:1978 the whole process 1962:1978 the whole process 1962:1978 The wide and accurate investigation of the different aspects related to the whole process represents a relevant point of novelty in this research field and suggests the operational conditions for the start-up of an open pond system for wastewater treatment and biomass production for further applications. 24622847 6 52 from inefficiency 1064:1075 arg1 terms 1080:1084 terms 1080:1084 terms of ammonia removal 1080:1103 %) was achieved at 1.5-day HRT, even if, under this condition, a clear inefficiency in terms of ammonia removal was observed. 24622847 12 53 from point 2002:2006 arg1 field 2036:2040 this research field 2022:2040 this research field 2022:2040 The wide and accurate investigation of the different aspects related to the whole process represents a relevant point of novelty in this research field and suggests the operational conditions for the start-up of an open pond system for wastewater treatment and biomass production for further applications. 24622847 5 54 theme proteins 975:982 arg1 content 964:970 the maximum content 952:970 the maximum content of proteins (26.9 wt 952:991 %) was obtained at high HRT (5 day); the maximum content of proteins (26.9 wt. 24622847 7 55 theme photosynthetic 1206:1219 arg1 response 1221:1228 the photosynthetic response 1202:1228 the photosynthetic response 1202:1228 Moreover the accumulation of N-NH3 occurring at 1.5-day HRT caused the decrease of the photosynthetic response in terms of efficiency of light capture (α) and relative electron transport rate (rETR), both parameters extracted from the rapid light curves (RLC) measurements. 24622847 10 56 theme maximum 1727:1733 arg1 content 1735:1741 a maximum content 1725:1741 a maximum content of 9.7 wt 1725:1751 On the other hand, in the two-phases process, when a nutrient deprivation condition was induced by diluting the culture with the secondary wastewater effluent, the algal cells accumulated TFAs, achieving a maximum content of 9.7 wt. 24622847 12 57 theme different 1933:1941 arg1 aspects 1943:1949 the different aspects 1929:1949 the different aspects related to the whole process 1929:1978 The wide and accurate investigation of the different aspects related to the whole process represents a relevant point of novelty in this research field and suggests the operational conditions for the start-up of an open pond system for wastewater treatment and biomass production for further applications. 24622847 1 58 theme nutrient 238:245 arg1 efficiency 255:264 the nutrient removal efficiency 234:264 the nutrient removal efficiency 234:264 The objective of the present study was to evaluate the nutrient removal efficiency and the physiological responses in terms of growth, biochemical composition and photosynthetic activity of the autochthonous freshwater algal strain Desmodesmus communis. 24622847 10 59 theme nutrient 1574:1581 arg1 condition 1595:1603 a nutrient deprivation condition 1572:1603 a nutrient deprivation condition 1572:1603 On the other hand, in the two-phases process, when a nutrient deprivation condition was induced by diluting the culture with the secondary wastewater effluent, the algal cells accumulated TFAs, achieving a maximum content of 9.7 wt. 24622847 3 60 theme dilution 716:723 arg1 rate 725:728 the different dilution rate 702:728 the different dilution rate 702:728 Semi-continuous cultures were operated for 7 day at 5-, 3- and 1.5-day HRT and the different dilution rate showed a greater influence on the biomass composition and nutrient removal efficiency. 24622847 12 61 theme system 2115:2120 arg1 start-up 2090:2097 the start-up 2086:2097 the start-up of an open pond system for wastewater treatment and biomass production for further applications 2086:2193 The wide and accurate investigation of the different aspects related to the whole process represents a relevant point of novelty in this research field and suggests the operational conditions for the start-up of an open pond system for wastewater treatment and biomass production for further applications. 24622847 4 62 theme polysaccharides 890:904 arg1 % 856:856 99 % 853:856 99 % 853:856 Removal of N-NH3 and P-PO4 was over 99 % and the highest accumulation of polysaccharides (57.2 wt. 24622847 4 62 theme polysaccharides 890:904 arg1 polysaccharides 890:904 polysaccharides 890:904 polysaccharides (57.2 wt 890:913 Removal of N-NH3 and P-PO4 was over 99 % and the highest accumulation of polysaccharides (57.2 wt. 24622847 4 62 theme polysaccharides 890:904 arg1 accumulation 874:885 the highest accumulation 862:885 the highest accumulation of polysaccharides (57.2 wt 862:913 Removal of N-NH3 and P-PO4 was over 99 % and the highest accumulation of polysaccharides (57.2 wt. 24622847 7 63 from decrease 1190:1197 arg1 terms 1233:1237 terms 1233:1237 terms of efficiency of light capture (α) and relative electron transport rate (rETR) 1233:1316 Moreover the accumulation of N-NH3 occurring at 1.5-day HRT caused the decrease of the photosynthetic response in terms of efficiency of light capture (α) and relative electron transport rate (rETR), both parameters extracted from the rapid light curves (RLC) measurements. 24622847 7 64 theme rapid 1354:1358 arg1 measurements 1379:1390 the rapid light curves (RLC) measurements 1350:1390 the rapid light curves (RLC) measurements 1350:1390 Moreover the accumulation of N-NH3 occurring at 1.5-day HRT caused the decrease of the photosynthetic response in terms of efficiency of light capture (α) and relative electron transport rate (rETR), both parameters extracted from the rapid light curves (RLC) measurements. 24622847 7 65 theme light 1360:1364 arg1 measurements 1379:1390 the rapid light curves (RLC) measurements 1350:1390 the rapid light curves (RLC) measurements 1350:1390 Moreover the accumulation of N-NH3 occurring at 1.5-day HRT caused the decrease of the photosynthetic response in terms of efficiency of light capture (α) and relative electron transport rate (rETR), both parameters extracted from the rapid light curves (RLC) measurements. 24622847 9 66 dep % 1495:1495 arg1 condition 1510:1518 each HRT condition 1501:1518 each HRT condition 1501:1518 % for each HRT condition. 24622847 3 67 theme greater 739:745 arg1 influence 747:755 a greater influence 737:755 a greater influence on the biomass composition and nutrient removal efficiency 737:814 Semi-continuous cultures were operated for 7 day at 5-, 3- and 1.5-day HRT and the different dilution rate showed a greater influence on the biomass composition and nutrient removal efficiency. 24622847 1 68 from responses 288:296 arg1 terms 301:305 terms 301:305 terms of growth, biochemical composition and photosynthetic activity of the autochthonous freshwater algal strain Desmodesmus communis 301:434 The objective of the present study was to evaluate the nutrient removal efficiency and the physiological responses in terms of growth, biochemical composition and photosynthetic activity of the autochthonous freshwater algal strain Desmodesmus communis. 24622847 11 69 theme algal 1846:1850 arg1 strain 1852:1857 this algal strain 1841:1857 this algal strain 1841:1857 % and a great increment in terms of biomass (1.64 ± 0.02 g L(-1)) due to the ability of this algal strain to accumulate intracellular N. 24622847 3 70 dep composition 772:782 arg1 the 760:762 the 760:762 the 760:762 Semi-continuous cultures were operated for 7 day at 5-, 3- and 1.5-day HRT and the different dilution rate showed a greater influence on the biomass composition and nutrient removal efficiency. 24622847 6 71 theme ammonia 1089:1095 arg1 removal 1097:1103 ammonia removal 1089:1103 ammonia removal 1089:1103 %) was achieved at 1.5-day HRT, even if, under this condition, a clear inefficiency in terms of ammonia removal was observed. 24622847 3 72 from influence 747:755 arg1 efficiency 805:814 the biomass composition and nutrient removal efficiency 760:814 the biomass composition and nutrient removal efficiency 760:814 Semi-continuous cultures were operated for 7 day at 5-, 3- and 1.5-day HRT and the different dilution rate showed a greater influence on the biomass composition and nutrient removal efficiency. 24622847 0 73 theme different 134:142 arg1 sources 144:150 different sources 134:150 different sources of urban wastewater effluents 134:180 Nutrient removal efficiency and physiological responses of Desmodesmus communis at different HRTs and nutrient stress condition using different sources of urban wastewater effluents. 24622847 1 74 theme present 204:210 arg1 study 212:216 the present study 200:216 the present study 200:216 The objective of the present study was to evaluate the nutrient removal efficiency and the physiological responses in terms of growth, biochemical composition and photosynthetic activity of the autochthonous freshwater algal strain Desmodesmus communis. 24622847 0 75 from HRTs 93:96 arg1 efficiency 17:26 Nutrient removal efficiency 0:26 Nutrient removal efficiency 0:26 Nutrient removal efficiency and physiological responses of Desmodesmus communis at different HRTs and nutrient stress condition using different sources of urban wastewater effluents. 24622847 0 75 from HRTs 93:96 arg1 responses 46:54 physiological responses 32:54 physiological responses 32:54 Nutrient removal efficiency and physiological responses of Desmodesmus communis at different HRTs and nutrient stress condition using different sources of urban wastewater effluents. 24622847 12 76 theme accurate 1903:1910 arg1 investigation 1912:1924 The wide and accurate investigation 1890:1924 The wide and accurate investigation of the different aspects related to the whole process 1890:1978 The wide and accurate investigation of the different aspects related to the whole process represents a relevant point of novelty in this research field and suggests the operational conditions for the start-up of an open pond system for wastewater treatment and biomass production for further applications. 24622847 3 77 theme biomass 764:770 arg1 composition 772:782 biomass composition 764:782 biomass composition 764:782 Semi-continuous cultures were operated for 7 day at 5-, 3- and 1.5-day HRT and the different dilution rate showed a greater influence on the biomass composition and nutrient removal efficiency. 24622847 1 78 from efficiency 255:264 arg1 terms 301:305 terms 301:305 terms of growth, biochemical composition and photosynthetic activity of the autochthonous freshwater algal strain Desmodesmus communis 301:434 The objective of the present study was to evaluate the nutrient removal efficiency and the physiological responses in terms of growth, biochemical composition and photosynthetic activity of the autochthonous freshwater algal strain Desmodesmus communis. 24622847 5 79 dep proteins 975:982 arg1 26.9 wt 985:991 26.9 wt 985:991 26.9 wt 985:991 %) was obtained at high HRT (5 day); the maximum content of proteins (26.9 wt. 24622847 0 80 theme wastewater 161:170 arg1 effluents 172:180 urban wastewater effluents 155:180 urban wastewater effluents 155:180 Nutrient removal efficiency and physiological responses of Desmodesmus communis at different HRTs and nutrient stress condition using different sources of urban wastewater effluents. 24622847 10 81 theme wastewater 1660:1669 arg1 effluent 1671:1678 the secondary wastewater effluent 1646:1678 the secondary wastewater effluent 1646:1678 On the other hand, in the two-phases process, when a nutrient deprivation condition was induced by diluting the culture with the secondary wastewater effluent, the algal cells accumulated TFAs, achieving a maximum content of 9.7 wt. 24622847 2 82 theme wastewater 601:610 arg1 effluents 612:620 both primary and secondary wastewater effluents 574:620 both primary and secondary wastewater effluents 574:620 Microalgae were grown in a primary municipal effluent under different hydraulic retention times (HRTs) and in a two-phases process using both primary and secondary wastewater effluents. 24622847 0 83 from condition 118:126 arg1 efficiency 17:26 Nutrient removal efficiency 0:26 Nutrient removal efficiency 0:26 Nutrient removal efficiency and physiological responses of Desmodesmus communis at different HRTs and nutrient stress condition using different sources of urban wastewater effluents. 24622847 0 83 from condition 118:126 arg1 responses 46:54 physiological responses 32:54 physiological responses 32:54 Nutrient removal efficiency and physiological responses of Desmodesmus communis at different HRTs and nutrient stress condition using different sources of urban wastewater effluents. 24622847 7 84 theme rate 1306:1309 arg1 efficiency 1242:1251 efficiency 1242:1251 efficiency of light capture (α) and relative electron transport rate (rETR) 1242:1316 Moreover the accumulation of N-NH3 occurring at 1.5-day HRT caused the decrease of the photosynthetic response in terms of efficiency of light capture (α) and relative electron transport rate (rETR), both parameters extracted from the rapid light curves (RLC) measurements. 24622847 3 85 theme removal 797:803 arg1 efficiency 805:814 the biomass composition and nutrient removal efficiency 760:814 the biomass composition and nutrient removal efficiency 760:814 Semi-continuous cultures were operated for 7 day at 5-, 3- and 1.5-day HRT and the different dilution rate showed a greater influence on the biomass composition and nutrient removal efficiency. 24622847 12 86 theme wastewater 2126:2135 arg1 treatment 2137:2145 wastewater treatment 2126:2145 wastewater treatment 2126:2145 The wide and accurate investigation of the different aspects related to the whole process represents a relevant point of novelty in this research field and suggests the operational conditions for the start-up of an open pond system for wastewater treatment and biomass production for further applications. 24622847 7 87 theme electron 1287:1294 arg1 rate 1306:1309 relative electron transport rate 1278:1309 relative electron transport rate (rETR) 1278:1316 Moreover the accumulation of N-NH3 occurring at 1.5-day HRT caused the decrease of the photosynthetic response in terms of efficiency of light capture (α) and relative electron transport rate (rETR), both parameters extracted from the rapid light curves (RLC) measurements. 24622847 7 87 theme electron 1287:1294 arg1 rETR 1312:1315 rETR 1312:1315 rETR 1312:1315 Moreover the accumulation of N-NH3 occurring at 1.5-day HRT caused the decrease of the photosynthetic response in terms of efficiency of light capture (α) and relative electron transport rate (rETR), both parameters extracted from the rapid light curves (RLC) measurements. 24622847 12 88 theme wide 1894:1897 arg1 investigation 1912:1924 The wide and accurate investigation 1890:1924 The wide and accurate investigation of the different aspects related to the whole process 1890:1978 The wide and accurate investigation of the different aspects related to the whole process represents a relevant point of novelty in this research field and suggests the operational conditions for the start-up of an open pond system for wastewater treatment and biomass production for further applications. 24622847 7 89 theme 1.5-day 1167:1173 arg1 HRT 1175:1177 1.5-day HRT 1167:1177 1.5-day HRT 1167:1177 Moreover the accumulation of N-NH3 occurring at 1.5-day HRT caused the decrease of the photosynthetic response in terms of efficiency of light capture (α) and relative electron transport rate (rETR), both parameters extracted from the rapid light curves (RLC) measurements. 24622847 11 90 theme intracellular 1873:1885 arg1 N 1887:1887 intracellular N 1873:1887 intracellular N 1873:1887 % and a great increment in terms of biomass (1.64 ± 0.02 g L(-1)) due to the ability of this algal strain to accumulate intracellular N. 24622847 10 91 theme algal 1685:1689 arg1 cells 1691:1695 the algal cells 1681:1695 the algal cells 1681:1695 On the other hand, in the two-phases process, when a nutrient deprivation condition was induced by diluting the culture with the secondary wastewater effluent, the algal cells accumulated TFAs, achieving a maximum content of 9.7 wt. 24622847 1 92 theme photosynthetic 346:359 arg1 activity 361:368 photosynthetic activity 346:368 photosynthetic activity 346:368 The objective of the present study was to evaluate the nutrient removal efficiency and the physiological responses in terms of growth, biochemical composition and photosynthetic activity of the autochthonous freshwater algal strain Desmodesmus communis. 24622847 10 93 with culture 1633:1639 arg1 effluent 1671:1678 the secondary wastewater effluent 1646:1678 the secondary wastewater effluent 1646:1678 On the other hand, in the two-phases process, when a nutrient deprivation condition was induced by diluting the culture with the secondary wastewater effluent, the algal cells accumulated TFAs, achieving a maximum content of 9.7 wt. 24622847 12 94 theme open 2105:2108 arg1 system 2115:2120 an open pond system 2102:2120 an open pond system for wastewater treatment and biomass production for further applications 2102:2193 The wide and accurate investigation of the different aspects related to the whole process represents a relevant point of novelty in this research field and suggests the operational conditions for the start-up of an open pond system for wastewater treatment and biomass production for further applications. 24622847 0 95 theme nutrient 102:109 arg1 condition 118:126 nutrient stress condition 102:126 nutrient stress condition 102:126 Nutrient removal efficiency and physiological responses of Desmodesmus communis at different HRTs and nutrient stress condition using different sources of urban wastewater effluents. 24622847 11 96 dep increment 1767:1775 arg1 -1 1814:1815 -1 1814:1815 -1 1814:1815 % and a great increment in terms of biomass (1.64 ± 0.02 g L(-1)) due to the ability of this algal strain to accumulate intracellular N. 24622847 11 96 dep increment 1767:1775 arg1 1.64 ± 0.02 g L 1798:1812 1.64 ± 0.02 g L 1798:1812 1.64 ± 0.02 g L(-1) 1798:1816 % and a great increment in terms of biomass (1.64 ± 0.02 g L(-1)) due to the ability of this algal strain to accumulate intracellular N. 24622847 1 97 theme autochthonous 377:389 arg1 strain 408:413 the autochthonous freshwater algal strain 373:413 the autochthonous freshwater algal strain 373:413 The objective of the present study was to evaluate the nutrient removal efficiency and the physiological responses in terms of growth, biochemical composition and photosynthetic activity of the autochthonous freshwater algal strain Desmodesmus communis. 24622847 5 98 theme maximum 956:962 arg1 content 964:970 the maximum content 952:970 the maximum content of proteins (26.9 wt 952:991 %) was obtained at high HRT (5 day); the maximum content of proteins (26.9 wt. 24622847 8 99 theme fatty 1448:1452 arg1 TFAs 1461:1464 TFAs 1461:1464 TFAs 1461:1464 No significant differences were observed for the total fatty acids (TFAs), with a content of 2-3.5 wt. 24622847 8 99 theme fatty 1448:1452 arg1 acids 1454:1458 the total fatty acids 1438:1458 the total fatty acids (TFAs) 1438:1465 No significant differences were observed for the total fatty acids (TFAs), with a content of 2-3.5 wt. 24622847 0 100 theme removal 9:15 arg1 efficiency 17:26 Nutrient removal efficiency 0:26 Nutrient removal efficiency 0:26 Nutrient removal efficiency and physiological responses of Desmodesmus communis at different HRTs and nutrient stress condition using different sources of urban wastewater effluents. 24622847 1 101 theme algal 402:406 arg1 strain 408:413 the autochthonous freshwater algal strain 373:413 the autochthonous freshwater algal strain 373:413 The objective of the present study was to evaluate the nutrient removal efficiency and the physiological responses in terms of growth, biochemical composition and photosynthetic activity of the autochthonous freshwater algal strain Desmodesmus communis. 24622847 7 102 theme light 1256:1260 arg1 capture 1262:1268 light capture 1256:1268 light capture (α) 1256:1272 Moreover the accumulation of N-NH3 occurring at 1.5-day HRT caused the decrease of the photosynthetic response in terms of efficiency of light capture (α) and relative electron transport rate (rETR), both parameters extracted from the rapid light curves (RLC) measurements. 24622847 7 102 theme light 1256:1260 arg1 α 1271:1271 α 1271:1271 α 1271:1271 Moreover the accumulation of N-NH3 occurring at 1.5-day HRT caused the decrease of the photosynthetic response in terms of efficiency of light capture (α) and relative electron transport rate (rETR), both parameters extracted from the rapid light curves (RLC) measurements. 24622847 2 103 theme municipal 472:480 arg1 effluent 482:489 a primary municipal effluent 462:489 a primary municipal effluent 462:489 Microalgae were grown in a primary municipal effluent under different hydraulic retention times (HRTs) and in a two-phases process using both primary and secondary wastewater effluents. 24622847 12 104 theme novelty 2011:2017 arg1 point 2002:2006 a relevant point 1991:2006 a relevant point of novelty in this research field 1991:2040 The wide and accurate investigation of the different aspects related to the whole process represents a relevant point of novelty in this research field and suggests the operational conditions for the start-up of an open pond system for wastewater treatment and biomass production for further applications. 24622847 7 105 dep decrease 1190:1197 arg1 both 1319:1322 both 1319:1322 both 1319:1322 Moreover the accumulation of N-NH3 occurring at 1.5-day HRT caused the decrease of the photosynthetic response in terms of efficiency of light capture (α) and relative electron transport rate (rETR), both parameters extracted from the rapid light curves (RLC) measurements. 24622847 7 106 theme efficiency 1242:1251 arg1 terms 1233:1237 terms 1233:1237 terms of efficiency of light capture (α) and relative electron transport rate (rETR) 1233:1316 Moreover the accumulation of N-NH3 occurring at 1.5-day HRT caused the decrease of the photosynthetic response in terms of efficiency of light capture (α) and relative electron transport rate (rETR), both parameters extracted from the rapid light curves (RLC) measurements. 24622847 2 107 theme hydraulic 507:515 arg1 HRTs 534:537 HRTs 534:537 HRTs 534:537 Microalgae were grown in a primary municipal effluent under different hydraulic retention times (HRTs) and in a two-phases process using both primary and secondary wastewater effluents. 24622847 2 107 theme hydraulic 507:515 arg1 times 527:531 different hydraulic retention times 497:531 different hydraulic retention times (HRTs) 497:538 Microalgae were grown in a primary municipal effluent under different hydraulic retention times (HRTs) and in a two-phases process using both primary and secondary wastewater effluents. 24622847 4 108 theme P-PO4 838:842 arg1 Removal 817:823 Removal 817:823 Removal of N-NH3 and P-PO4 817:842 Removal of N-NH3 and P-PO4 was over 99 % and the highest accumulation of polysaccharides (57.2 wt. 24622847 7 109 theme response 1221:1228 arg1 decrease 1190:1197 the decrease 1186:1197 the decrease of the photosynthetic response in terms of efficiency of light capture (α) and relative electron transport rate (rETR) 1186:1316 Moreover the accumulation of N-NH3 occurring at 1.5-day HRT caused the decrease of the photosynthetic response in terms of efficiency of light capture (α) and relative electron transport rate (rETR), both parameters extracted from the rapid light curves (RLC) measurements. 24622847 10 110 theme 9.7 wt 1746:1751 arg1 content 1735:1741 a maximum content 1725:1741 a maximum content of 9.7 wt 1725:1751 On the other hand, in the two-phases process, when a nutrient deprivation condition was induced by diluting the culture with the secondary wastewater effluent, the algal cells accumulated TFAs, achieving a maximum content of 9.7 wt. 24622847 1 111 theme composition 330:340 arg1 terms 301:305 terms 301:305 terms of growth, biochemical composition and photosynthetic activity of the autochthonous freshwater algal strain Desmodesmus communis 301:434 The objective of the present study was to evaluate the nutrient removal efficiency and the physiological responses in terms of growth, biochemical composition and photosynthetic activity of the autochthonous freshwater algal strain Desmodesmus communis. 24622847 6 112 theme clear 1058:1062 arg1 inefficiency 1064:1075 a clear inefficiency 1056:1075 a clear inefficiency in terms of ammonia removal 1056:1103 %) was achieved at 1.5-day HRT, even if, under this condition, a clear inefficiency in terms of ammonia removal was observed. 24622847 8 113 theme 2-3.5 wt 1486:1493 arg1 content 1475:1481 a content 1473:1481 a content of 2-3.5 wt 1473:1493 No significant differences were observed for the total fatty acids (TFAs), with a content of 2-3.5 wt. 24622847 3 114 theme 1.5-day 686:692 arg1 HRT 694:696 1.5-day HRT 686:696 1.5-day HRT 686:696 Semi-continuous cultures were operated for 7 day at 5-, 3- and 1.5-day HRT and the different dilution rate showed a greater influence on the biomass composition and nutrient removal efficiency. 24622847 10 115 theme two-phases 1547:1556 arg1 process 1558:1564 the two-phases process 1543:1564 the two-phases process 1543:1564 On the other hand, in the two-phases process, when a nutrient deprivation condition was induced by diluting the culture with the secondary wastewater effluent, the algal cells accumulated TFAs, achieving a maximum content of 9.7 wt. 24622847 9 116 theme HRT 1506:1508 arg1 condition 1510:1518 each HRT condition 1501:1518 each HRT condition 1501:1518 % for each HRT condition. 24622847 4 117 theme N-NH3 828:832 arg1 Removal 817:823 Removal 817:823 Removal of N-NH3 and P-PO4 817:842 Removal of N-NH3 and P-PO4 was over 99 % and the highest accumulation of polysaccharides (57.2 wt. 24622847 10 118 theme deprivation 1583:1593 arg1 condition 1595:1603 a nutrient deprivation condition 1572:1603 a nutrient deprivation condition 1572:1603 On the other hand, in the two-phases process, when a nutrient deprivation condition was induced by diluting the culture with the secondary wastewater effluent, the algal cells accumulated TFAs, achieving a maximum content of 9.7 wt. 24622847 1 119 theme removal 247:253 arg1 efficiency 255:264 the nutrient removal efficiency 234:264 the nutrient removal efficiency 234:264 The objective of the present study was to evaluate the nutrient removal efficiency and the physiological responses in terms of growth, biochemical composition and photosynthetic activity of the autochthonous freshwater algal strain Desmodesmus communis. 26082402 8 0 from overexpression 1184:1197 arg1 Arabidopsis 1254:1264 Arabidopsis 1254:1264 Arabidopsis 1254:1264 In addition, overexpression of both CYP75B4 and CYP93G1 (a flavone synthase II) in Arabidopsis resulted in tricin accumulation. 26082402 13 1 theme activity 1836:1843 arg1 Recruitment 1785:1795 Recruitment 1785:1795 Recruitment of chrysoeriol-specific 5'-hydroxylase activity by an ancestral CYP75B sequence 1785:1875 Recruitment of chrysoeriol-specific 5'-hydroxylase activity by an ancestral CYP75B sequence may represent a key event leading to the prevalence of tricin-derived metabolites in grasses and other monocots today. 26082402 6 2 theme unusual 857:863 arg1 accumulation 865:876 unusual accumulation 857:876 unusual accumulation of chrysoeriol (a 3'-methoxylated flavone) 857:919 A CYP75B4 knockout mutant is tricin deficient, with unusual accumulation of chrysoeriol (a 3'-methoxylated flavone). 26082402 11 3 theme tricetin 1569:1576 arg1 chrysoeriol 1545:1555 chrysoeriol 1545:1555 chrysoeriol 1545:1555 Hence, chrysoeriol, instead of tricetin, is an intermediate in tricin biosynthesis. 26082402 11 3 theme tricetin 1569:1576 arg1 intermediate 1585:1596 an intermediate 1582:1596 an intermediate in tricin biosynthesis 1582:1619 Hence, chrysoeriol, instead of tricetin, is an intermediate in tricin biosynthesis. 26082402 12 4 theme CYP75B 1742:1747 arg1 sequences 1774:1782 the canonical CYP75B flavonoid 3'-hydroxylase sequences 1728:1782 the canonical CYP75B flavonoid 3'-hydroxylase sequences 1728:1782 CYP75B4 homologous sequences are highly conserved in Poaceae, and they are phylogenetically distinct from the canonical CYP75B flavonoid 3'-hydroxylase sequences. 26082402 7 5 theme transparent 1078:1088 arg1 mutants 1097:1103 Arabidopsis (Arabidopsis thaliana) transparent testa7 mutants 1043:1103 Arabidopsis (Arabidopsis thaliana) transparent testa7 mutants 1043:1103 CYP75B4 functions as a bona fide flavonoid 3'-hydroxylase by restoring the accumulation of 3'-hydroxylated flavonoids in Arabidopsis (Arabidopsis thaliana) transparent testa7 mutants and catalyzing in vitro 3'-hydroxylation of different flavonoids. 26082402 7 5 theme transparent 1078:1088 arg1 thaliana 1068:1075 Arabidopsis thaliana 1056:1075 Arabidopsis thaliana 1056:1075 CYP75B4 functions as a bona fide flavonoid 3'-hydroxylase by restoring the accumulation of 3'-hydroxylated flavonoids in Arabidopsis (Arabidopsis thaliana) transparent testa7 mutants and catalyzing in vitro 3'-hydroxylation of different flavonoids. 26082402 8 6 theme CYP75B4 1207:1213 arg1 overexpression 1184:1197 overexpression 1184:1197 overexpression of both CYP75B4 and CYP93G1 (a flavone synthase II) in Arabidopsis 1184:1264 In addition, overexpression of both CYP75B4 and CYP93G1 (a flavone synthase II) in Arabidopsis resulted in tricin accumulation. 26082402 12 7 theme 3'-hydroxylase 1759:1772 arg1 sequences 1774:1782 the canonical CYP75B flavonoid 3'-hydroxylase sequences 1728:1782 the canonical CYP75B flavonoid 3'-hydroxylase sequences 1728:1782 CYP75B4 homologous sequences are highly conserved in Poaceae, and they are phylogenetically distinct from the canonical CYP75B flavonoid 3'-hydroxylase sequences. 26082402 13 8 theme chrysoeriol-specific 1800:1819 arg1 activity 1836:1843 chrysoeriol-specific 5'-hydroxylase activity 1800:1843 chrysoeriol-specific 5'-hydroxylase activity 1800:1843 Recruitment of chrysoeriol-specific 5'-hydroxylase activity by an ancestral CYP75B sequence may represent a key event leading to the prevalence of tricin-derived metabolites in grasses and other monocots today. 26082402 8 9 theme CYP93G1 1219:1225 arg1 overexpression 1184:1197 overexpression 1184:1197 overexpression of both CYP75B4 and CYP93G1 (a flavone synthase II) in Arabidopsis 1184:1264 In addition, overexpression of both CYP75B4 and CYP93G1 (a flavone synthase II) in Arabidopsis resulted in tricin accumulation. 26082402 0 10 from 75B4 67:70 arg1 Completion 0:9 Completion 0:9 Completion of Tricin Biosynthesis Pathway in Rice: Cytochrome P450 75B4 0:70 Completion of Tricin Biosynthesis Pathway in Rice: Cytochrome P450 75B4 Is a Unique Chrysoeriol 5'-Hydroxylase. 26082402 0 10 from 75B4 67:70 arg1 5'-Hydroxylase 96:109 a Unique Chrysoeriol 5'-Hydroxylase 75:109 a Unique Chrysoeriol 5'-Hydroxylase 75:109 Completion of Tricin Biosynthesis Pathway in Rice: Cytochrome P450 75B4 Is a Unique Chrysoeriol 5'-Hydroxylase. 26082402 2 11 dep Oryza 287:291 arg1 sativa 293:298 Oryza sativa 287:298 Oryza sativa 287:298 Recently, we demonstrated that the rice (Oryza sativa) cytochrome P450 enzymes CYP93G1 and CYP93G2 channel flavanones en route to flavone O-linked conjugates and C-glycosides, respectively. 26082402 6 12 theme 3'-methoxylated 896:910 arg1 chrysoeriol 881:891 chrysoeriol 881:891 chrysoeriol (a 3'-methoxylated flavone) 881:919 A CYP75B4 knockout mutant is tricin deficient, with unusual accumulation of chrysoeriol (a 3'-methoxylated flavone). 26082402 6 12 theme 3'-methoxylated 896:910 arg1 flavone 912:918 a 3'-methoxylated flavone 894:918 a 3'-methoxylated flavone 894:918 A CYP75B4 knockout mutant is tricin deficient, with unusual accumulation of chrysoeriol (a 3'-methoxylated flavone). 26082402 7 13 theme 3'-hydroxylated 1013:1027 arg1 flavonoids 1029:1038 3'-hydroxylated flavonoids 1013:1038 3'-hydroxylated flavonoids 1013:1038 CYP75B4 functions as a bona fide flavonoid 3'-hydroxylase by restoring the accumulation of 3'-hydroxylated flavonoids in Arabidopsis (Arabidopsis thaliana) transparent testa7 mutants and catalyzing in vitro 3'-hydroxylation of different flavonoids. 26082402 7 14 theme flavonoid 955:963 arg1 3'-hydroxylase 965:978 a bona fide flavonoid 3'-hydroxylase 943:978 a bona fide flavonoid 3'-hydroxylase 943:978 CYP75B4 functions as a bona fide flavonoid 3'-hydroxylase by restoring the accumulation of 3'-hydroxylated flavonoids in Arabidopsis (Arabidopsis thaliana) transparent testa7 mutants and catalyzing in vitro 3'-hydroxylation of different flavonoids. 26082402 7 14 theme flavonoid 955:963 arg1 CYP75B4 922:928 CYP75B4 922:928 CYP75B4 922:928 CYP75B4 functions as a bona fide flavonoid 3'-hydroxylase by restoring the accumulation of 3'-hydroxylated flavonoids in Arabidopsis (Arabidopsis thaliana) transparent testa7 mutants and catalyzing in vitro 3'-hydroxylation of different flavonoids. 26082402 12 15 theme canonical 1732:1740 arg1 sequences 1774:1782 the canonical CYP75B flavonoid 3'-hydroxylase sequences 1728:1782 the canonical CYP75B flavonoid 3'-hydroxylase sequences 1728:1782 CYP75B4 homologous sequences are highly conserved in Poaceae, and they are phylogenetically distinct from the canonical CYP75B flavonoid 3'-hydroxylase sequences. 26082402 13 16 theme monocots 1980:1987 arg1 today 1989:1993 grasses and other monocots today 1962:1993 grasses and other monocots today 1962:1993 Recruitment of chrysoeriol-specific 5'-hydroxylase activity by an ancestral CYP75B sequence may represent a key event leading to the prevalence of tricin-derived metabolites in grasses and other monocots today. 26082402 0 17 theme Cytochrome 51:60 arg1 75B4 67:70 Rice: Cytochrome P450 75B4 45:70 Rice: Cytochrome P450 75B4 45:70 Completion of Tricin Biosynthesis Pathway in Rice: Cytochrome P450 75B4 Is a Unique Chrysoeriol 5'-Hydroxylase. 26082402 7 18 theme bona 945:948 arg1 3'-hydroxylase 965:978 a bona fide flavonoid 3'-hydroxylase 943:978 a bona fide flavonoid 3'-hydroxylase 943:978 CYP75B4 functions as a bona fide flavonoid 3'-hydroxylase by restoring the accumulation of 3'-hydroxylated flavonoids in Arabidopsis (Arabidopsis thaliana) transparent testa7 mutants and catalyzing in vitro 3'-hydroxylation of different flavonoids. 26082402 7 18 theme bona 945:948 arg1 CYP75B4 922:928 CYP75B4 922:928 CYP75B4 922:928 CYP75B4 functions as a bona fide flavonoid 3'-hydroxylase by restoring the accumulation of 3'-hydroxylated flavonoids in Arabidopsis (Arabidopsis thaliana) transparent testa7 mutants and catalyzing in vitro 3'-hydroxylation of different flavonoids. 26082402 13 19 theme tricin-derived 1932:1945 arg1 metabolites 1947:1957 tricin-derived metabolites 1932:1957 tricin-derived metabolites 1932:1957 Recruitment of chrysoeriol-specific 5'-hydroxylase activity by an ancestral CYP75B sequence may represent a key event leading to the prevalence of tricin-derived metabolites in grasses and other monocots today. 26082402 5 20 theme flavonoid 732:740 arg1 hydroxylase 749:759 a unique flavonoid B-ring hydroxylase 723:759 a unique flavonoid B-ring hydroxylase indispensable for tricin formation in rice 723:802 However, we report here that CYP75B4 a unique flavonoid B-ring hydroxylase indispensable for tricin formation in rice. 26082402 0 21 from Completion 0:9 arg1 75B4 67:70 Rice: Cytochrome P450 75B4 45:70 Rice: Cytochrome P450 75B4 45:70 Completion of Tricin Biosynthesis Pathway in Rice: Cytochrome P450 75B4 Is a Unique Chrysoeriol 5'-Hydroxylase. 26082402 2 22 theme flavone 376:382 arg1 conjugates 393:402 flavone O-linked conjugates 376:402 flavone O-linked conjugates 376:402 Recently, we demonstrated that the rice (Oryza sativa) cytochrome P450 enzymes CYP93G1 and CYP93G2 channel flavanones en route to flavone O-linked conjugates and C-glycosides, respectively. 26082402 0 23 theme Chrysoeriol 84:94 arg1 Completion 0:9 Completion 0:9 Completion of Tricin Biosynthesis Pathway in Rice: Cytochrome P450 75B4 0:70 Completion of Tricin Biosynthesis Pathway in Rice: Cytochrome P450 75B4 Is a Unique Chrysoeriol 5'-Hydroxylase. 26082402 0 23 theme Chrysoeriol 84:94 arg1 5'-Hydroxylase 96:109 a Unique Chrysoeriol 5'-Hydroxylase 75:109 a Unique Chrysoeriol 5'-Hydroxylase 75:109 Completion of Tricin Biosynthesis Pathway in Rice: Cytochrome P450 75B4 Is a Unique Chrysoeriol 5'-Hydroxylase. 26082402 9 24 theme chrysoeriol 1328:1338 arg1 5'-hydroxylation 1308:1323 Specific 5'-hydroxylation 1299:1323 Specific 5'-hydroxylation of chrysoeriol to selgin by CYP75B4 1299:1359 Specific 5'-hydroxylation of chrysoeriol to selgin by CYP75B4 was further demonstrated in vitro. 26082402 5 25 theme B-ring 742:747 arg1 hydroxylase 749:759 a unique flavonoid B-ring hydroxylase 723:759 a unique flavonoid B-ring hydroxylase indispensable for tricin formation in rice 723:802 However, we report here that CYP75B4 a unique flavonoid B-ring hydroxylase indispensable for tricin formation in rice. 26082402 0 26 from Pathway 34:40 arg1 75B4 67:70 Rice: Cytochrome P450 75B4 45:70 Rice: Cytochrome P450 75B4 45:70 Completion of Tricin Biosynthesis Pathway in Rice: Cytochrome P450 75B4 Is a Unique Chrysoeriol 5'-Hydroxylase. 26082402 10 27 theme → 1483:1483 arg1 steps 1409:1413 The reaction steps 1396:1413 The reaction steps leading to tricin biosynthesis 1396:1444 The reaction steps leading to tricin biosynthesis are then reconstructed as naringenin → apigenin → luteolin → chrysoeriol → selgin → tricin. 26082402 10 27 theme → 1483:1483 arg1 apigenin 1485:1492 naringenin → apigenin 1472:1492 naringenin → apigenin 1472:1492 The reaction steps leading to tricin biosynthesis are then reconstructed as naringenin → apigenin → luteolin → chrysoeriol → selgin → tricin. 26082402 4 28 theme flavonoid 534:542 arg1 5'-hydroxylases 547:561 flavonoid 3',5'-hydroxylases 534:561 5'-hydroxylases 547:561 Previously, flavonoid 3',5'-hydroxylases belonging to the CYP75A subfamily were believed to generate tricetin from apigenin for 3',5'-O-methylation to form tricin. 26082402 10 29 theme → 1519:1519 arg1 steps 1409:1413 The reaction steps 1396:1413 The reaction steps leading to tricin biosynthesis 1396:1444 The reaction steps leading to tricin biosynthesis are then reconstructed as naringenin → apigenin → luteolin → chrysoeriol → selgin → tricin. 26082402 10 29 theme → 1519:1519 arg1 tricin 1530:1535 luteolin → chrysoeriol → selgin → tricin 1496:1535 luteolin → chrysoeriol → selgin → tricin 1496:1535 The reaction steps leading to tricin biosynthesis are then reconstructed as naringenin → apigenin → luteolin → chrysoeriol → selgin → tricin. 26082402 0 30 theme Tricin 14:19 arg1 Pathway 34:40 Tricin Biosynthesis Pathway 14:40 Tricin Biosynthesis Pathway in Rice: Cytochrome P450 75B4 14:70 Completion of Tricin Biosynthesis Pathway in Rice: Cytochrome P450 75B4 Is a Unique Chrysoeriol 5'-Hydroxylase. 26082402 10 31 theme → 1505:1505 arg1 steps 1409:1413 The reaction steps 1396:1413 The reaction steps leading to tricin biosynthesis 1396:1444 The reaction steps leading to tricin biosynthesis are then reconstructed as naringenin → apigenin → luteolin → chrysoeriol → selgin → tricin. 26082402 10 31 theme → 1505:1505 arg1 tricin 1530:1535 luteolin → chrysoeriol → selgin → tricin 1496:1535 luteolin → chrysoeriol → selgin → tricin 1496:1535 The reaction steps leading to tricin biosynthesis are then reconstructed as naringenin → apigenin → luteolin → chrysoeriol → selgin → tricin. 26082402 7 32 theme flavonoids 1159:1168 arg1 3'-hydroxylation 1129:1144 in vitro 3'-hydroxylation 1120:1144 in vitro 3'-hydroxylation of different flavonoids 1120:1168 CYP75B4 functions as a bona fide flavonoid 3'-hydroxylase by restoring the accumulation of 3'-hydroxylated flavonoids in Arabidopsis (Arabidopsis thaliana) transparent testa7 mutants and catalyzing in vitro 3'-hydroxylation of different flavonoids. 26082402 0 33 theme Pathway 34:40 arg1 Completion 0:9 Completion 0:9 Completion of Tricin Biosynthesis Pathway in Rice: Cytochrome P450 75B4 0:70 Completion of Tricin Biosynthesis Pathway in Rice: Cytochrome P450 75B4 Is a Unique Chrysoeriol 5'-Hydroxylase. 26082402 0 33 theme Pathway 34:40 arg1 5'-Hydroxylase 96:109 a Unique Chrysoeriol 5'-Hydroxylase 75:109 a Unique Chrysoeriol 5'-Hydroxylase 75:109 Completion of Tricin Biosynthesis Pathway in Rice: Cytochrome P450 75B4 Is a Unique Chrysoeriol 5'-Hydroxylase. 26082402 3 34 theme 5'-dimethoxyflavone 454:472 arg1 nucleus 474:480 5'-dimethoxyflavone nucleus 454:480 5'-dimethoxyflavone nucleus 454:480 In tricin, the 3',5'-dimethoxyflavone nucleus is formed before O-linked conjugations. 26082402 0 35 theme Rice 45:48 arg1 75B4 67:70 Rice: Cytochrome P450 75B4 45:70 Rice: Cytochrome P450 75B4 45:70 Completion of Tricin Biosynthesis Pathway in Rice: Cytochrome P450 75B4 Is a Unique Chrysoeriol 5'-Hydroxylase. 26082402 6 36 theme knockout 815:822 arg1 mutant 824:829 A CYP75B4 knockout mutant 805:829 A CYP75B4 knockout mutant 805:829 A CYP75B4 knockout mutant is tricin deficient, with unusual accumulation of chrysoeriol (a 3'-methoxylated flavone). 26082402 6 36 theme knockout 815:822 arg1 deficient 841:849 tricin deficient 834:849 tricin deficient 834:849 A CYP75B4 knockout mutant is tricin deficient, with unusual accumulation of chrysoeriol (a 3'-methoxylated flavone). 26082402 10 37 theme → 1528:1528 arg1 steps 1409:1413 The reaction steps 1396:1413 The reaction steps leading to tricin biosynthesis 1396:1444 The reaction steps leading to tricin biosynthesis are then reconstructed as naringenin → apigenin → luteolin → chrysoeriol → selgin → tricin. 26082402 10 37 theme → 1528:1528 arg1 tricin 1530:1535 luteolin → chrysoeriol → selgin → tricin 1496:1535 luteolin → chrysoeriol → selgin → tricin 1496:1535 The reaction steps leading to tricin biosynthesis are then reconstructed as naringenin → apigenin → luteolin → chrysoeriol → selgin → tricin. 26082402 2 38 link O-linked 384:391 arg1 conjugates 393:402 flavone O-linked conjugates 376:402 flavone O-linked conjugates 376:402 Recently, we demonstrated that the rice (Oryza sativa) cytochrome P450 enzymes CYP93G1 and CYP93G2 channel flavanones en route to flavone O-linked conjugates and C-glycosides, respectively. 26082402 2 39 theme P450 312:315 arg1 enzymes 317:323 the rice (Oryza sativa) cytochrome P450 enzymes 277:323 the rice (Oryza sativa) cytochrome P450 enzymes CYP93G1 and CYP93G2 channel flavanones 277:362 Recently, we demonstrated that the rice (Oryza sativa) cytochrome P450 enzymes CYP93G1 and CYP93G2 channel flavanones en route to flavone O-linked conjugates and C-glycosides, respectively. 26082402 2 39 theme P450 312:315 arg1 Oryza 287:291 Oryza 287:291 Oryza 287:291 Recently, we demonstrated that the rice (Oryza sativa) cytochrome P450 enzymes CYP93G1 and CYP93G2 channel flavanones en route to flavone O-linked conjugates and C-glycosides, respectively. 26082402 13 40 from prevalence 1918:1927 arg1 today 1989:1993 grasses and other monocots today 1962:1993 grasses and other monocots today 1962:1993 Recruitment of chrysoeriol-specific 5'-hydroxylase activity by an ancestral CYP75B sequence may represent a key event leading to the prevalence of tricin-derived metabolites in grasses and other monocots today. 26082402 4 41 theme CYP75A 580:585 arg1 subfamily 587:595 the CYP75A subfamily 576:595 the CYP75A subfamily 576:595 Previously, flavonoid 3',5'-hydroxylases belonging to the CYP75A subfamily were believed to generate tricetin from apigenin for 3',5'-O-methylation to form tricin. 26082402 13 42 theme ancestral 1851:1859 arg1 sequence 1868:1875 an ancestral CYP75B sequence 1848:1875 an ancestral CYP75B sequence 1848:1875 Recruitment of chrysoeriol-specific 5'-hydroxylase activity by an ancestral CYP75B sequence may represent a key event leading to the prevalence of tricin-derived metabolites in grasses and other monocots today. 26082402 1 43 theme recent 232:237 arg1 years 239:243 recent years 232:243 recent years 232:243 Flavones are ubiquitously accumulated in land plants, but their biosynthesis in monocots remained largely elusive until recent years. 26082402 7 44 theme in 1120:1121 arg1 3'-hydroxylation 1129:1144 in vitro 3'-hydroxylation 1120:1144 in vitro 3'-hydroxylation of different flavonoids 1120:1168 CYP75B4 functions as a bona fide flavonoid 3'-hydroxylase by restoring the accumulation of 3'-hydroxylated flavonoids in Arabidopsis (Arabidopsis thaliana) transparent testa7 mutants and catalyzing in vitro 3'-hydroxylation of different flavonoids. 26082402 2 45 theme CYP93G2 337:343 arg1 flavanones 353:362 CYP93G2 channel flavanones 337:362 CYP93G2 channel flavanones 337:362 Recently, we demonstrated that the rice (Oryza sativa) cytochrome P450 enzymes CYP93G1 and CYP93G2 channel flavanones en route to flavone O-linked conjugates and C-glycosides, respectively. 26082402 6 46 theme chrysoeriol 881:891 arg1 accumulation 865:876 unusual accumulation 857:876 unusual accumulation of chrysoeriol (a 3'-methoxylated flavone) 857:919 A CYP75B4 knockout mutant is tricin deficient, with unusual accumulation of chrysoeriol (a 3'-methoxylated flavone). 26082402 13 47 theme 5'-hydroxylase 1821:1834 arg1 activity 1836:1843 chrysoeriol-specific 5'-hydroxylase activity 1800:1843 chrysoeriol-specific 5'-hydroxylase activity 1800:1843 Recruitment of chrysoeriol-specific 5'-hydroxylase activity by an ancestral CYP75B sequence may represent a key event leading to the prevalence of tricin-derived metabolites in grasses and other monocots today. 26082402 10 48 theme reaction 1400:1407 arg1 apigenin 1485:1492 naringenin → apigenin 1472:1492 naringenin → apigenin 1472:1492 The reaction steps leading to tricin biosynthesis are then reconstructed as naringenin → apigenin → luteolin → chrysoeriol → selgin → tricin. 26082402 10 48 theme reaction 1400:1407 arg1 steps 1409:1413 The reaction steps 1396:1413 The reaction steps leading to tricin biosynthesis 1396:1444 The reaction steps leading to tricin biosynthesis are then reconstructed as naringenin → apigenin → luteolin → chrysoeriol → selgin → tricin. 26082402 10 48 theme reaction 1400:1407 arg1 tricin 1530:1535 luteolin → chrysoeriol → selgin → tricin 1496:1535 luteolin → chrysoeriol → selgin → tricin 1496:1535 The reaction steps leading to tricin biosynthesis are then reconstructed as naringenin → apigenin → luteolin → chrysoeriol → selgin → tricin. 26082402 2 49 theme rice 281:284 arg1 enzymes 317:323 the rice (Oryza sativa) cytochrome P450 enzymes 277:323 the rice (Oryza sativa) cytochrome P450 enzymes CYP93G1 and CYP93G2 channel flavanones 277:362 Recently, we demonstrated that the rice (Oryza sativa) cytochrome P450 enzymes CYP93G1 and CYP93G2 channel flavanones en route to flavone O-linked conjugates and C-glycosides, respectively. 26082402 2 49 theme rice 281:284 arg1 Oryza 287:291 Oryza 287:291 Oryza 287:291 Recently, we demonstrated that the rice (Oryza sativa) cytochrome P450 enzymes CYP93G1 and CYP93G2 channel flavanones en route to flavone O-linked conjugates and C-glycosides, respectively. 26082402 7 50 theme testa7 1090:1095 arg1 mutants 1097:1103 Arabidopsis (Arabidopsis thaliana) transparent testa7 mutants 1043:1103 Arabidopsis (Arabidopsis thaliana) transparent testa7 mutants 1043:1103 CYP75B4 functions as a bona fide flavonoid 3'-hydroxylase by restoring the accumulation of 3'-hydroxylated flavonoids in Arabidopsis (Arabidopsis thaliana) transparent testa7 mutants and catalyzing in vitro 3'-hydroxylation of different flavonoids. 26082402 7 50 theme testa7 1090:1095 arg1 thaliana 1068:1075 Arabidopsis thaliana 1056:1075 Arabidopsis thaliana 1056:1075 CYP75B4 functions as a bona fide flavonoid 3'-hydroxylase by restoring the accumulation of 3'-hydroxylated flavonoids in Arabidopsis (Arabidopsis thaliana) transparent testa7 mutants and catalyzing in vitro 3'-hydroxylation of different flavonoids. 26082402 12 51 theme flavonoid 1749:1757 arg1 sequences 1774:1782 the canonical CYP75B flavonoid 3'-hydroxylase sequences 1728:1782 the canonical CYP75B flavonoid 3'-hydroxylase sequences 1728:1782 CYP75B4 homologous sequences are highly conserved in Poaceae, and they are phylogenetically distinct from the canonical CYP75B flavonoid 3'-hydroxylase sequences. 26082402 8 52 theme flavone 1230:1236 arg1 CYP93G1 1219:1225 CYP93G1 1219:1225 CYP93G1 (a flavone synthase II) 1219:1249 In addition, overexpression of both CYP75B4 and CYP93G1 (a flavone synthase II) in Arabidopsis resulted in tricin accumulation. 26082402 8 52 theme flavone 1230:1236 arg1 synthase 1238:1245 a flavone synthase II 1228:1248 a flavone synthase II 1228:1248 In addition, overexpression of both CYP75B4 and CYP93G1 (a flavone synthase II) in Arabidopsis resulted in tricin accumulation. 26082402 10 53 theme tricin 1426:1431 arg1 biosynthesis 1433:1444 tricin biosynthesis 1426:1444 tricin biosynthesis 1426:1444 The reaction steps leading to tricin biosynthesis are then reconstructed as naringenin → apigenin → luteolin → chrysoeriol → selgin → tricin. 26082402 4 54 from apigenin 637:644 arg1 tricetin 623:630 tricetin 623:630 tricetin from apigenin for 3',5'-O-methylation to form tricin 623:683 Previously, flavonoid 3',5'-hydroxylases belonging to the CYP75A subfamily were believed to generate tricetin from apigenin for 3',5'-O-methylation to form tricin. 26082402 7 55 dep in 1120:1121 arg1 vitro 1123:1127 vitro 1123:1127 vitro 1123:1127 CYP75B4 functions as a bona fide flavonoid 3'-hydroxylase by restoring the accumulation of 3'-hydroxylated flavonoids in Arabidopsis (Arabidopsis thaliana) transparent testa7 mutants and catalyzing in vitro 3'-hydroxylation of different flavonoids. 26082402 7 56 theme Arabidopsis 1056:1066 arg1 mutants 1097:1103 Arabidopsis (Arabidopsis thaliana) transparent testa7 mutants 1043:1103 Arabidopsis (Arabidopsis thaliana) transparent testa7 mutants 1043:1103 CYP75B4 functions as a bona fide flavonoid 3'-hydroxylase by restoring the accumulation of 3'-hydroxylated flavonoids in Arabidopsis (Arabidopsis thaliana) transparent testa7 mutants and catalyzing in vitro 3'-hydroxylation of different flavonoids. 26082402 7 56 theme Arabidopsis 1056:1066 arg1 thaliana 1068:1075 Arabidopsis thaliana 1056:1075 Arabidopsis thaliana 1056:1075 CYP75B4 functions as a bona fide flavonoid 3'-hydroxylase by restoring the accumulation of 3'-hydroxylated flavonoids in Arabidopsis (Arabidopsis thaliana) transparent testa7 mutants and catalyzing in vitro 3'-hydroxylation of different flavonoids. 26082402 12 57 theme CYP75B4 1622:1628 arg1 sequences 1641:1649 CYP75B4 homologous sequences 1622:1649 CYP75B4 homologous sequences 1622:1649 CYP75B4 homologous sequences are highly conserved in Poaceae, and they are phylogenetically distinct from the canonical CYP75B flavonoid 3'-hydroxylase sequences. 26082402 7 58 theme Arabidopsis 1043:1053 arg1 mutants 1097:1103 Arabidopsis (Arabidopsis thaliana) transparent testa7 mutants 1043:1103 Arabidopsis (Arabidopsis thaliana) transparent testa7 mutants 1043:1103 CYP75B4 functions as a bona fide flavonoid 3'-hydroxylase by restoring the accumulation of 3'-hydroxylated flavonoids in Arabidopsis (Arabidopsis thaliana) transparent testa7 mutants and catalyzing in vitro 3'-hydroxylation of different flavonoids. 26082402 7 58 theme Arabidopsis 1043:1053 arg1 thaliana 1068:1075 Arabidopsis thaliana 1056:1075 Arabidopsis thaliana 1056:1075 CYP75B4 functions as a bona fide flavonoid 3'-hydroxylase by restoring the accumulation of 3'-hydroxylated flavonoids in Arabidopsis (Arabidopsis thaliana) transparent testa7 mutants and catalyzing in vitro 3'-hydroxylation of different flavonoids. 26082402 11 59 from intermediate 1585:1596 arg1 biosynthesis 1608:1619 tricin biosynthesis 1601:1619 tricin biosynthesis 1601:1619 Hence, chrysoeriol, instead of tricetin, is an intermediate in tricin biosynthesis. 26082402 3 60 link O-linked 499:506 arg1 conjugations 508:519 O-linked conjugations 499:519 O-linked conjugations 499:519 In tricin, the 3',5'-dimethoxyflavone nucleus is formed before O-linked conjugations. 26082402 7 61 from accumulation 997:1008 arg1 mutants 1097:1103 Arabidopsis (Arabidopsis thaliana) transparent testa7 mutants 1043:1103 Arabidopsis (Arabidopsis thaliana) transparent testa7 mutants 1043:1103 CYP75B4 functions as a bona fide flavonoid 3'-hydroxylase by restoring the accumulation of 3'-hydroxylated flavonoids in Arabidopsis (Arabidopsis thaliana) transparent testa7 mutants and catalyzing in vitro 3'-hydroxylation of different flavonoids. 26082402 7 61 from accumulation 997:1008 arg1 thaliana 1068:1075 Arabidopsis thaliana 1056:1075 Arabidopsis thaliana 1056:1075 CYP75B4 functions as a bona fide flavonoid 3'-hydroxylase by restoring the accumulation of 3'-hydroxylated flavonoids in Arabidopsis (Arabidopsis thaliana) transparent testa7 mutants and catalyzing in vitro 3'-hydroxylation of different flavonoids. 26082402 7 62 theme flavonoids 1029:1038 arg1 accumulation 997:1008 the accumulation 993:1008 the accumulation of 3'-hydroxylated flavonoids in Arabidopsis (Arabidopsis thaliana) transparent testa7 mutants 993:1103 CYP75B4 functions as a bona fide flavonoid 3'-hydroxylase by restoring the accumulation of 3'-hydroxylated flavonoids in Arabidopsis (Arabidopsis thaliana) transparent testa7 mutants and catalyzing in vitro 3'-hydroxylation of different flavonoids. 26082402 13 63 link tricin-derived 1932:1945 arg1 metabolites 1947:1957 tricin-derived metabolites 1932:1957 tricin-derived metabolites 1932:1957 Recruitment of chrysoeriol-specific 5'-hydroxylase activity by an ancestral CYP75B sequence may represent a key event leading to the prevalence of tricin-derived metabolites in grasses and other monocots today. 26082402 8 64 theme tricin 1278:1283 arg1 accumulation 1285:1296 tricin accumulation 1278:1296 tricin accumulation 1278:1296 In addition, overexpression of both CYP75B4 and CYP93G1 (a flavone synthase II) in Arabidopsis resulted in tricin accumulation. 26082402 13 65 theme grasses 1962:1968 arg1 today 1989:1993 grasses and other monocots today 1962:1993 grasses and other monocots today 1962:1993 Recruitment of chrysoeriol-specific 5'-hydroxylase activity by an ancestral CYP75B sequence may represent a key event leading to the prevalence of tricin-derived metabolites in grasses and other monocots today. 26082402 13 66 theme other 1974:1978 arg1 monocots 1980:1987 other monocots 1974:1987 other monocots 1974:1987 Recruitment of chrysoeriol-specific 5'-hydroxylase activity by an ancestral CYP75B sequence may represent a key event leading to the prevalence of tricin-derived metabolites in grasses and other monocots today. 26082402 0 67 theme P450 62:65 arg1 75B4 67:70 Rice: Cytochrome P450 75B4 45:70 Rice: Cytochrome P450 75B4 45:70 Completion of Tricin Biosynthesis Pathway in Rice: Cytochrome P450 75B4 Is a Unique Chrysoeriol 5'-Hydroxylase. 26082402 1 68 from biosynthesis 176:187 arg1 monocots 192:199 monocots 192:199 monocots 192:199 Flavones are ubiquitously accumulated in land plants, but their biosynthesis in monocots remained largely elusive until recent years. 26082402 5 69 theme unique 725:730 arg1 hydroxylase 749:759 a unique flavonoid B-ring hydroxylase 723:759 a unique flavonoid B-ring hydroxylase indispensable for tricin formation in rice 723:802 However, we report here that CYP75B4 a unique flavonoid B-ring hydroxylase indispensable for tricin formation in rice. 26082402 1 70 theme land 153:156 arg1 plants 158:163 land plants 153:163 land plants 153:163 Flavones are ubiquitously accumulated in land plants, but their biosynthesis in monocots remained largely elusive until recent years. 26082402 13 71 theme metabolites 1947:1957 arg1 prevalence 1918:1927 the prevalence 1914:1927 the prevalence of tricin-derived metabolites in grasses and other monocots today 1914:1993 Recruitment of chrysoeriol-specific 5'-hydroxylase activity by an ancestral CYP75B sequence may represent a key event leading to the prevalence of tricin-derived metabolites in grasses and other monocots today. 26082402 0 72 theme Unique 77:82 arg1 Completion 0:9 Completion 0:9 Completion of Tricin Biosynthesis Pathway in Rice: Cytochrome P450 75B4 0:70 Completion of Tricin Biosynthesis Pathway in Rice: Cytochrome P450 75B4 Is a Unique Chrysoeriol 5'-Hydroxylase. 26082402 0 72 theme Unique 77:82 arg1 5'-Hydroxylase 96:109 a Unique Chrysoeriol 5'-Hydroxylase 75:109 a Unique Chrysoeriol 5'-Hydroxylase 75:109 Completion of Tricin Biosynthesis Pathway in Rice: Cytochrome P450 75B4 Is a Unique Chrysoeriol 5'-Hydroxylase. 26082402 9 73 theme Specific 1299:1306 arg1 5'-hydroxylation 1308:1323 Specific 5'-hydroxylation 1299:1323 Specific 5'-hydroxylation of chrysoeriol to selgin by CYP75B4 1299:1359 Specific 5'-hydroxylation of chrysoeriol to selgin by CYP75B4 was further demonstrated in vitro. 26082402 4 74 dep 5'-O-methylation 653:668 arg1 form 673:676 form 673:676 to form tricin 670:683 Previously, flavonoid 3',5'-hydroxylases belonging to the CYP75A subfamily were believed to generate tricetin from apigenin for 3',5'-O-methylation to form tricin. 26082402 5 75 theme tricin 779:784 arg1 formation 786:794 tricin formation 779:794 tricin formation in rice 779:802 However, we report here that CYP75B4 a unique flavonoid B-ring hydroxylase indispensable for tricin formation in rice. 26082402 5 76 from formation 786:794 arg1 rice 799:802 rice 799:802 rice 799:802 However, we report here that CYP75B4 a unique flavonoid B-ring hydroxylase indispensable for tricin formation in rice. 26082402 6 77 with deficient 841:849 arg1 accumulation 865:876 unusual accumulation 857:876 unusual accumulation of chrysoeriol (a 3'-methoxylated flavone) 857:919 A CYP75B4 knockout mutant is tricin deficient, with unusual accumulation of chrysoeriol (a 3'-methoxylated flavone). 26082402 10 78 theme naringenin 1472:1481 arg1 steps 1409:1413 The reaction steps 1396:1413 The reaction steps leading to tricin biosynthesis 1396:1444 The reaction steps leading to tricin biosynthesis are then reconstructed as naringenin → apigenin → luteolin → chrysoeriol → selgin → tricin. 26082402 10 78 theme naringenin 1472:1481 arg1 apigenin 1485:1492 naringenin → apigenin 1472:1492 naringenin → apigenin 1472:1492 The reaction steps leading to tricin biosynthesis are then reconstructed as naringenin → apigenin → luteolin → chrysoeriol → selgin → tricin. 26082402 7 79 dep bona 945:948 arg1 fide 950:953 fide 950:953 fide 950:953 CYP75B4 functions as a bona fide flavonoid 3'-hydroxylase by restoring the accumulation of 3'-hydroxylated flavonoids in Arabidopsis (Arabidopsis thaliana) transparent testa7 mutants and catalyzing in vitro 3'-hydroxylation of different flavonoids. 26082402 0 80 theme Biosynthesis 21:32 arg1 Pathway 34:40 Tricin Biosynthesis Pathway 14:40 Tricin Biosynthesis Pathway in Rice: Cytochrome P450 75B4 14:70 Completion of Tricin Biosynthesis Pathway in Rice: Cytochrome P450 75B4 Is a Unique Chrysoeriol 5'-Hydroxylase. 26082402 12 81 theme homologous 1630:1639 arg1 sequences 1641:1649 CYP75B4 homologous sequences 1622:1649 CYP75B4 homologous sequences 1622:1649 CYP75B4 homologous sequences are highly conserved in Poaceae, and they are phylogenetically distinct from the canonical CYP75B flavonoid 3'-hydroxylase sequences. 26082402 12 82 from sequences 1774:1782 arg1 distinct 1714:1721 distinct 1714:1721 distinct 1714:1721 CYP75B4 homologous sequences are highly conserved in Poaceae, and they are phylogenetically distinct from the canonical CYP75B flavonoid 3'-hydroxylase sequences. 26082402 10 83 theme chrysoeriol 1507:1517 arg1 steps 1409:1413 The reaction steps 1396:1413 The reaction steps leading to tricin biosynthesis 1396:1444 The reaction steps leading to tricin biosynthesis are then reconstructed as naringenin → apigenin → luteolin → chrysoeriol → selgin → tricin. 26082402 10 83 theme chrysoeriol 1507:1517 arg1 tricin 1530:1535 luteolin → chrysoeriol → selgin → tricin 1496:1535 luteolin → chrysoeriol → selgin → tricin 1496:1535 The reaction steps leading to tricin biosynthesis are then reconstructed as naringenin → apigenin → luteolin → chrysoeriol → selgin → tricin. 26082402 2 84 dep enzymes 317:323 arg1 CYP93G1 325:331 CYP93G1 325:331 CYP93G1 325:331 Recently, we demonstrated that the rice (Oryza sativa) cytochrome P450 enzymes CYP93G1 and CYP93G2 channel flavanones en route to flavone O-linked conjugates and C-glycosides, respectively. 26082402 2 84 dep enzymes 317:323 arg1 flavanones 353:362 CYP93G2 channel flavanones 337:362 CYP93G2 channel flavanones 337:362 Recently, we demonstrated that the rice (Oryza sativa) cytochrome P450 enzymes CYP93G1 and CYP93G2 channel flavanones en route to flavone O-linked conjugates and C-glycosides, respectively. 26082402 13 85 theme key 1893:1895 arg1 event 1897:1901 a key event 1891:1901 a key event leading to the prevalence of tricin-derived metabolites in grasses and other monocots today 1891:1993 Recruitment of chrysoeriol-specific 5'-hydroxylase activity by an ancestral CYP75B sequence may represent a key event leading to the prevalence of tricin-derived metabolites in grasses and other monocots today. 26082402 7 86 theme different 1149:1157 arg1 flavonoids 1159:1168 different flavonoids 1149:1168 different flavonoids 1149:1168 CYP75B4 functions as a bona fide flavonoid 3'-hydroxylase by restoring the accumulation of 3'-hydroxylated flavonoids in Arabidopsis (Arabidopsis thaliana) transparent testa7 mutants and catalyzing in vitro 3'-hydroxylation of different flavonoids. 26082402 6 87 theme tricin 834:839 arg1 mutant 824:829 A CYP75B4 knockout mutant 805:829 A CYP75B4 knockout mutant 805:829 A CYP75B4 knockout mutant is tricin deficient, with unusual accumulation of chrysoeriol (a 3'-methoxylated flavone). 26082402 6 87 theme tricin 834:839 arg1 deficient 841:849 tricin deficient 834:849 tricin deficient 834:849 A CYP75B4 knockout mutant is tricin deficient, with unusual accumulation of chrysoeriol (a 3'-methoxylated flavone). 26082402 10 88 theme luteolin 1496:1503 arg1 steps 1409:1413 The reaction steps 1396:1413 The reaction steps leading to tricin biosynthesis 1396:1444 The reaction steps leading to tricin biosynthesis are then reconstructed as naringenin → apigenin → luteolin → chrysoeriol → selgin → tricin. 26082402 10 88 theme luteolin 1496:1503 arg1 tricin 1530:1535 luteolin → chrysoeriol → selgin → tricin 1496:1535 luteolin → chrysoeriol → selgin → tricin 1496:1535 The reaction steps leading to tricin biosynthesis are then reconstructed as naringenin → apigenin → luteolin → chrysoeriol → selgin → tricin. 26082402 2 89 theme O-linked 384:391 arg1 conjugates 393:402 flavone O-linked conjugates 376:402 flavone O-linked conjugates 376:402 Recently, we demonstrated that the rice (Oryza sativa) cytochrome P450 enzymes CYP93G1 and CYP93G2 channel flavanones en route to flavone O-linked conjugates and C-glycosides, respectively. 26082402 5 90 theme indispensable 761:773 arg1 hydroxylase 749:759 a unique flavonoid B-ring hydroxylase 723:759 a unique flavonoid B-ring hydroxylase indispensable for tricin formation in rice 723:802 However, we report here that CYP75B4 a unique flavonoid B-ring hydroxylase indispensable for tricin formation in rice. 26082402 2 91 theme channel 345:351 arg1 flavanones 353:362 CYP93G2 channel flavanones 337:362 CYP93G2 channel flavanones 337:362 Recently, we demonstrated that the rice (Oryza sativa) cytochrome P450 enzymes CYP93G1 and CYP93G2 channel flavanones en route to flavone O-linked conjugates and C-glycosides, respectively. 26082402 6 92 theme CYP75B4 807:813 arg1 mutant 824:829 A CYP75B4 knockout mutant 805:829 A CYP75B4 knockout mutant 805:829 A CYP75B4 knockout mutant is tricin deficient, with unusual accumulation of chrysoeriol (a 3'-methoxylated flavone). 26082402 6 92 theme CYP75B4 807:813 arg1 deficient 841:849 tricin deficient 834:849 tricin deficient 834:849 A CYP75B4 knockout mutant is tricin deficient, with unusual accumulation of chrysoeriol (a 3'-methoxylated flavone). 26082402 10 93 theme selgin 1521:1526 arg1 steps 1409:1413 The reaction steps 1396:1413 The reaction steps leading to tricin biosynthesis 1396:1444 The reaction steps leading to tricin biosynthesis are then reconstructed as naringenin → apigenin → luteolin → chrysoeriol → selgin → tricin. 26082402 10 93 theme selgin 1521:1526 arg1 tricin 1530:1535 luteolin → chrysoeriol → selgin → tricin 1496:1535 luteolin → chrysoeriol → selgin → tricin 1496:1535 The reaction steps leading to tricin biosynthesis are then reconstructed as naringenin → apigenin → luteolin → chrysoeriol → selgin → tricin. 26082402 2 94 theme cytochrome 301:310 arg1 enzymes 317:323 the rice (Oryza sativa) cytochrome P450 enzymes 277:323 the rice (Oryza sativa) cytochrome P450 enzymes CYP93G1 and CYP93G2 channel flavanones 277:362 Recently, we demonstrated that the rice (Oryza sativa) cytochrome P450 enzymes CYP93G1 and CYP93G2 channel flavanones en route to flavone O-linked conjugates and C-glycosides, respectively. 26082402 2 94 theme cytochrome 301:310 arg1 Oryza 287:291 Oryza 287:291 Oryza 287:291 Recently, we demonstrated that the rice (Oryza sativa) cytochrome P450 enzymes CYP93G1 and CYP93G2 channel flavanones en route to flavone O-linked conjugates and C-glycosides, respectively. 26082402 13 95 theme CYP75B 1861:1866 arg1 sequence 1868:1875 an ancestral CYP75B sequence 1848:1875 an ancestral CYP75B sequence 1848:1875 Recruitment of chrysoeriol-specific 5'-hydroxylase activity by an ancestral CYP75B sequence may represent a key event leading to the prevalence of tricin-derived metabolites in grasses and other monocots today. 26082402 11 96 theme tricin 1601:1606 arg1 biosynthesis 1608:1619 tricin biosynthesis 1601:1619 tricin biosynthesis 1601:1619 Hence, chrysoeriol, instead of tricetin, is an intermediate in tricin biosynthesis. 26082402 3 97 theme O-linked 499:506 arg1 conjugations 508:519 O-linked conjugations 499:519 O-linked conjugations 499:519 In tricin, the 3',5'-dimethoxyflavone nucleus is formed before O-linked conjugations. 26707622 8 0 theme deletion 1328:1335 arg1 mutants 1337:1343 deletion mutants 1328:1343 deletion mutants of p120 1328:1351 To determine the domain of p120 involved in binding to OGT, a series of deletion mutants of p120 were constructed and subjected to protein binding assays by pull‑down assays. 26707622 13 1 theme interaction 2233:2243 arg1 regulation 2215:2224 the regulation 2211:2224 the regulation of the interaction between p120 and E‑cadherin, and thus E‑cadherin‑mediated cell‑cell adhesion, which has essential roles in cancer development and progression 2211:2385 The present study provided a novel underlying mechanism of the regulation of the interaction between p120 and E‑cadherin, and thus E‑cadherin‑mediated cell‑cell adhesion, which has essential roles in cancer development and progression. 26707622 2 2 theme O‑linked 365:372 arg1 O‑GlcNAc 395:402 O‑GlcNAc 395:402 O‑GlcNAc 395:402 A previous study by our group demonstrated that O‑linked N‑acetylglucosamine (O‑GlcNAc) is involved in the regulation of the interaction between p120 and E‑cadherin. 26707622 2 2 theme O‑linked 365:372 arg1 N‑acetylglucosamine 374:392 O‑linked N‑acetylglucosamine 365:392 O‑linked N‑acetylglucosamine (O‑GlcNAc) 365:403 A previous study by our group demonstrated that O‑linked N‑acetylglucosamine (O‑GlcNAc) is involved in the regulation of the interaction between p120 and E‑cadherin. 26707622 3 3 theme complex 684:690 arg1 formation 648:656 the formation 644:656 the formation of the E‑cadherin/catenin complex independent of its catalytic activity 644:728 As O‑GlcNAc transferase (OGT) is able to directly bind to the majority of its target proteins, the present study hypothesized that OGT may additionally regulate the formation of the E‑cadherin/catenin complex independent of its catalytic activity. 26707622 1 4 theme large 178:182 arg1 domain 209:214 a large central armadillo repeat domain 176:214 a large central armadillo repeat domain 176:214 p120-catenin (p120) contains a large central armadillo repeat domain, via which it binds to E‑cadherin to stabilize the latter, thereby regulating cell‑to‑cell adhesion. 26707622 10 5 theme DE3 1687:1689 arg1 cells 1712:1716 BL21 (DE3) recombinant E. coli cells 1681:1716 BL21 (DE3) recombinant E. coli cells 1681:1716 Finally, OGT, p120 and E‑cadherin cytoplasmic domains (ECD) were recombinantly expressed in BL21 (DE3) recombinant E. coli cells, and a glutathione S‑transferase (GST) pull‑down assay was performed to assess the interactions among the purified recombinant proteins. 26707622 3 6 theme independent 692:702 arg1 complex 684:690 the E‑cadherin/catenin complex 661:690 the E‑cadherin/catenin complex independent of its catalytic activity 661:728 As O‑GlcNAc transferase (OGT) is able to directly bind to the majority of its target proteins, the present study hypothesized that OGT may additionally regulate the formation of the E‑cadherin/catenin complex independent of its catalytic activity. 26707622 4 7 theme E‑cadherin/catenin 864:881 arg1 complex 883:889 the E‑cadherin/catenin complex 860:889 the E‑cadherin/catenin complex 860:889 To verify this hypothesis, a catalytically inactive OGT mutant was expressed in H1299 cells, and its effects on the formation of the E‑cadherin/catenin complex were assessed. 26707622 5 8 theme catalytic 1050:1058 arg1 activity 1060:1067 its catalytic activity 1046:1067 its catalytic activity 1046:1067 A cytoskeleton‑binding protein extraction assay confirmed that OGT inhibited the formation of the E‑cadherin/catenin complex independent of its catalytic activity. 26707622 8 9 theme p120 1348:1351 arg1 mutants 1337:1343 deletion mutants 1328:1343 deletion mutants of p120 1328:1351 To determine the domain of p120 involved in binding to OGT, a series of deletion mutants of p120 were constructed and subjected to protein binding assays by pull‑down assays. 26707622 13 10 theme present 2156:2162 arg1 study 2164:2168 The present study 2152:2168 The present study 2152:2168 The present study provided a novel underlying mechanism of the regulation of the interaction between p120 and E‑cadherin, and thus E‑cadherin‑mediated cell‑cell adhesion, which has essential roles in cancer development and progression. 26707622 2 11 link O‑linked 365:372 arg1 O‑GlcNAc 395:402 O‑GlcNAc 395:402 O‑GlcNAc 395:402 A previous study by our group demonstrated that O‑linked N‑acetylglucosamine (O‑GlcNAc) is involved in the regulation of the interaction between p120 and E‑cadherin. 26707622 2 11 link O‑linked 365:372 arg1 N‑acetylglucosamine 374:392 O‑linked N‑acetylglucosamine 365:392 O‑linked N‑acetylglucosamine (O‑GlcNAc) 365:403 A previous study by our group demonstrated that O‑linked N‑acetylglucosamine (O‑GlcNAc) is involved in the regulation of the interaction between p120 and E‑cadherin. 26707622 6 12 used used 1132:1135 arg2 assays 1120:1125 co‑immunoprecipitation and pull‑down assays 1083:1125 co‑immunoprecipitation and pull‑down assays 1083:1125 In addition, co‑immunoprecipitation and pull‑down assays were used to evaluate the interaction between OGT and p120. 26707622 8 13 theme mutants 1337:1343 arg1 series 1318:1323 a series 1316:1323 a series of deletion mutants of p120 1316:1351 To determine the domain of p120 involved in binding to OGT, a series of deletion mutants of p120 were constructed and subjected to protein binding assays by pull‑down assays. 26707622 12 14 theme E‑cadherin/catenin 2063:2080 arg1 complex 2082:2088 the E‑cadherin/catenin complex 2059:2088 the E‑cadherin/catenin complex 2059:2088 All of these results suggested that OGT inhibited the formation of the E‑cadherin/catenin complex through reducing the interaction between p120 and E‑cadherin. 26707622 0 15 theme activity 137:144 arg1 independent 108:118 independent 108:118 independent 108:118 Inhibition of E-cadherin/catenin complex formation by O-linked N-acetylglucosamine transferase is partially independent of its catalytic activity. 26707622 10 16 dep OGT 1598:1600 arg1 domains 1635:1641 cytoplasmic domains 1623:1641 cytoplasmic domains 1623:1641 Finally, OGT, p120 and E‑cadherin cytoplasmic domains (ECD) were recombinantly expressed in BL21 (DE3) recombinant E. coli cells, and a glutathione S‑transferase (GST) pull‑down assay was performed to assess the interactions among the purified recombinant proteins. 26707622 9 17 theme regulatory 1475:1484 arg1 p120 1511:1514 p120 1511:1514 p120 1511:1514 Immunoblotting showed that OGT bound to the regulatory and armadillo domains of p120, which might interfere with the interaction between p120 and E‑cadherin. 26707622 9 17 theme regulatory 1475:1484 arg1 domains 1500:1506 the regulatory and armadillo domains 1471:1506 the regulatory and armadillo domains 1471:1506 Immunoblotting showed that OGT bound to the regulatory and armadillo domains of p120, which might interfere with the interaction between p120 and E‑cadherin. 26707622 4 18 theme OGT 783:785 arg1 mutant 787:792 a catalytically inactive OGT mutant 758:792 a catalytically inactive OGT mutant 758:792 To verify this hypothesis, a catalytically inactive OGT mutant was expressed in H1299 cells, and its effects on the formation of the E‑cadherin/catenin complex were assessed. 26707622 11 19 theme maltose‑binding 1885:1899 arg1 MBP 1910:1912 MBP 1910:1912 MBP 1910:1912 Immunoblotting indicated that maltose‑binding protein (MBP)‑OGT inhibited the binding of His‑p120 to GST‑ECD in a dose‑dependent manner. 26707622 11 19 theme maltose‑binding 1885:1899 arg1 protein 1901:1907 maltose‑binding protein 1885:1907 maltose‑binding protein (MBP)‑OGT 1885:1917 Immunoblotting indicated that maltose‑binding protein (MBP)‑OGT inhibited the binding of His‑p120 to GST‑ECD in a dose‑dependent manner. 26707622 1 20 theme central 184:190 arg1 domain 209:214 a large central armadillo repeat domain 176:214 a large central armadillo repeat domain 176:214 p120-catenin (p120) contains a large central armadillo repeat domain, via which it binds to E‑cadherin to stabilize the latter, thereby regulating cell‑to‑cell adhesion. 26707622 0 21 theme catalytic 127:135 arg1 activity 137:144 its catalytic activity 123:144 its catalytic activity 123:144 Inhibition of E-cadherin/catenin complex formation by O-linked N-acetylglucosamine transferase is partially independent of its catalytic activity. 26707622 1 22 contain contains 167:174 arg1 p120 161:164 p120 161:164 p120 161:164 p120-catenin (p120) contains a large central armadillo repeat domain, via which it binds to E‑cadherin to stabilize the latter, thereby regulating cell‑to‑cell adhesion. 26707622 1 22 contain contains 167:174 arg2 domain 209:214 a large central armadillo repeat domain 176:214 a large central armadillo repeat domain 176:214 p120-catenin (p120) contains a large central armadillo repeat domain, via which it binds to E‑cadherin to stabilize the latter, thereby regulating cell‑to‑cell adhesion. 26707622 1 22 contain contains 167:174 arg1 p120-catenin 147:158 p120-catenin 147:158 p120-catenin (p120) 147:165 p120-catenin (p120) contains a large central armadillo repeat domain, via which it binds to E‑cadherin to stabilize the latter, thereby regulating cell‑to‑cell adhesion. 26707622 4 23 theme inactive 774:781 arg1 mutant 787:792 a catalytically inactive OGT mutant 758:792 a catalytically inactive OGT mutant 758:792 To verify this hypothesis, a catalytically inactive OGT mutant was expressed in H1299 cells, and its effects on the formation of the E‑cadherin/catenin complex were assessed. 26707622 1 24 theme armadillo 192:200 arg1 domain 209:214 a large central armadillo repeat domain 176:214 a large central armadillo repeat domain 176:214 p120-catenin (p120) contains a large central armadillo repeat domain, via which it binds to E‑cadherin to stabilize the latter, thereby regulating cell‑to‑cell adhesion. 26707622 10 25 theme S‑transferase 1737:1749 arg1 assay 1767:1771 a glutathione S‑transferase (GST) pull‑down assay 1723:1771 a glutathione S‑transferase (GST) pull‑down assay 1723:1771 Finally, OGT, p120 and E‑cadherin cytoplasmic domains (ECD) were recombinantly expressed in BL21 (DE3) recombinant E. coli cells, and a glutathione S‑transferase (GST) pull‑down assay was performed to assess the interactions among the purified recombinant proteins. 26707622 3 26 theme activity 721:728 arg1 independent 692:702 independent 692:702 independent 692:702 As O‑GlcNAc transferase (OGT) is able to directly bind to the majority of its target proteins, the present study hypothesized that OGT may additionally regulate the formation of the E‑cadherin/catenin complex independent of its catalytic activity. 26707622 0 27 link O-linked 54:61 arg1 transferase 83:93 O-linked N-acetylglucosamine transferase 54:93 O-linked N-acetylglucosamine transferase 54:93 Inhibition of E-cadherin/catenin complex formation by O-linked N-acetylglucosamine transferase is partially independent of its catalytic activity. 26707622 10 28 theme pull‑down 1757:1765 arg1 assay 1767:1771 a glutathione S‑transferase (GST) pull‑down assay 1723:1771 a glutathione S‑transferase (GST) pull‑down assay 1723:1771 Finally, OGT, p120 and E‑cadherin cytoplasmic domains (ECD) were recombinantly expressed in BL21 (DE3) recombinant E. coli cells, and a glutathione S‑transferase (GST) pull‑down assay was performed to assess the interactions among the purified recombinant proteins. 26707622 1 29 theme repeat 202:207 arg1 domain 209:214 a large central armadillo repeat domain 176:214 a large central armadillo repeat domain 176:214 p120-catenin (p120) contains a large central armadillo repeat domain, via which it binds to E‑cadherin to stabilize the latter, thereby regulating cell‑to‑cell adhesion. 26707622 13 30 theme E‑cadherin‑mediated 2283:2301 arg1 adhesion 2313:2320 E‑cadherin‑mediated cell‑cell adhesion 2283:2320 E‑cadherin‑mediated cell‑cell adhesion 2283:2320 The present study provided a novel underlying mechanism of the regulation of the interaction between p120 and E‑cadherin, and thus E‑cadherin‑mediated cell‑cell adhesion, which has essential roles in cancer development and progression. 26707622 2 31 theme previous 319:326 arg1 study 328:332 A previous study 317:332 A previous study by our group 317:345 A previous study by our group demonstrated that O‑linked N‑acetylglucosamine (O‑GlcNAc) is involved in the regulation of the interaction between p120 and E‑cadherin. 26707622 6 32 theme co‑immunoprecipitation 1083:1104 arg1 assays 1120:1125 co‑immunoprecipitation and pull‑down assays 1083:1125 co‑immunoprecipitation and pull‑down assays 1083:1125 In addition, co‑immunoprecipitation and pull‑down assays were used to evaluate the interaction between OGT and p120. 26707622 2 33 theme interaction 442:452 arg1 regulation 424:433 the regulation 420:433 the regulation of the interaction between p120 and E‑cadherin 420:480 A previous study by our group demonstrated that O‑linked N‑acetylglucosamine (O‑GlcNAc) is involved in the regulation of the interaction between p120 and E‑cadherin. 26707622 8 34 theme protein 1387:1393 arg1 assays 1403:1408 protein binding assays 1387:1408 protein binding assays 1387:1408 To determine the domain of p120 involved in binding to OGT, a series of deletion mutants of p120 were constructed and subjected to protein binding assays by pull‑down assays. 26707622 10 35 theme BL21 1681:1684 arg1 cells 1712:1716 BL21 (DE3) recombinant E. coli cells 1681:1716 BL21 (DE3) recombinant E. coli cells 1681:1716 Finally, OGT, p120 and E‑cadherin cytoplasmic domains (ECD) were recombinantly expressed in BL21 (DE3) recombinant E. coli cells, and a glutathione S‑transferase (GST) pull‑down assay was performed to assess the interactions among the purified recombinant proteins. 26707622 3 36 theme target 561:566 arg1 proteins 568:575 its target proteins 557:575 its target proteins 557:575 As O‑GlcNAc transferase (OGT) is able to directly bind to the majority of its target proteins, the present study hypothesized that OGT may additionally regulate the formation of the E‑cadherin/catenin complex independent of its catalytic activity. 26707622 1 37 theme cell‑to‑cell 294:305 arg1 adhesion 307:314 cell‑to‑cell adhesion 294:314 cell‑to‑cell adhesion 294:314 p120-catenin (p120) contains a large central armadillo repeat domain, via which it binds to E‑cadherin to stabilize the latter, thereby regulating cell‑to‑cell adhesion. 26707622 9 38 theme p120 1511:1514 arg1 p120 1511:1514 p120 1511:1514 p120 1511:1514 Immunoblotting showed that OGT bound to the regulatory and armadillo domains of p120, which might interfere with the interaction between p120 and E‑cadherin. 26707622 9 38 theme p120 1511:1514 arg1 domains 1500:1506 the regulatory and armadillo domains 1471:1506 the regulatory and armadillo domains 1471:1506 Immunoblotting showed that OGT bound to the regulatory and armadillo domains of p120, which might interfere with the interaction between p120 and E‑cadherin. 26707622 8 39 theme binding 1395:1401 arg1 assays 1403:1408 protein binding assays 1387:1408 protein binding assays 1387:1408 To determine the domain of p120 involved in binding to OGT, a series of deletion mutants of p120 were constructed and subjected to protein binding assays by pull‑down assays. 26707622 4 40 from effects 832:838 arg1 formation 847:855 the formation 843:855 the formation of the E‑cadherin/catenin complex 843:889 To verify this hypothesis, a catalytically inactive OGT mutant was expressed in H1299 cells, and its effects on the formation of the E‑cadherin/catenin complex were assessed. 26707622 10 41 theme glutathione 1725:1735 arg1 assay 1767:1771 a glutathione S‑transferase (GST) pull‑down assay 1723:1771 a glutathione S‑transferase (GST) pull‑down assay 1723:1771 Finally, OGT, p120 and E‑cadherin cytoplasmic domains (ECD) were recombinantly expressed in BL21 (DE3) recombinant E. coli cells, and a glutathione S‑transferase (GST) pull‑down assay was performed to assess the interactions among the purified recombinant proteins. 26707622 8 42 theme p120 1283:1286 arg1 domain 1273:1278 the domain 1269:1278 the domain of p120 involved in binding to OGT 1269:1313 To determine the domain of p120 involved in binding to OGT, a series of deletion mutants of p120 were constructed and subjected to protein binding assays by pull‑down assays. 26707622 8 42 theme p120 1283:1286 arg1 p120 1283:1286 p120 1283:1286 p120 1283:1286 To determine the domain of p120 involved in binding to OGT, a series of deletion mutants of p120 were constructed and subjected to protein binding assays by pull‑down assays. 26707622 13 43 theme essential 2333:2341 arg1 roles 2343:2347 essential roles 2333:2347 essential roles 2333:2347 The present study provided a novel underlying mechanism of the regulation of the interaction between p120 and E‑cadherin, and thus E‑cadherin‑mediated cell‑cell adhesion, which has essential roles in cancer development and progression. 26707622 5 44 theme independent 1031:1041 arg1 formation 987:995 the formation 983:995 the formation of the E‑cadherin/catenin complex independent of its catalytic activity 983:1067 A cytoskeleton‑binding protein extraction assay confirmed that OGT inhibited the formation of the E‑cadherin/catenin complex independent of its catalytic activity. 26707622 10 45 theme recombinant 1833:1843 arg1 proteins 1845:1852 the purified recombinant proteins 1820:1852 the purified recombinant proteins 1820:1852 Finally, OGT, p120 and E‑cadherin cytoplasmic domains (ECD) were recombinantly expressed in BL21 (DE3) recombinant E. coli cells, and a glutathione S‑transferase (GST) pull‑down assay was performed to assess the interactions among the purified recombinant proteins. 26707622 11 46 theme His‑p120 1944:1951 arg1 binding 1933:1939 the binding 1929:1939 the binding of His‑p120 to GST‑ECD 1929:1962 Immunoblotting indicated that maltose‑binding protein (MBP)‑OGT inhibited the binding of His‑p120 to GST‑ECD in a dose‑dependent manner. 26707622 11 47 theme protein 1901:1907 arg1 ‑OGT 1914:1917 maltose‑binding protein (MBP)‑OGT 1885:1917 maltose‑binding protein (MBP)‑OGT 1885:1917 Immunoblotting indicated that maltose‑binding protein (MBP)‑OGT inhibited the binding of His‑p120 to GST‑ECD in a dose‑dependent manner. 26707622 0 48 theme formation 41:49 arg1 Inhibition 0:9 Inhibition 0:9 Inhibition of E-cadherin/catenin complex formation by O-linked N-acetylglucosamine transferase 0:93 Inhibition of E-cadherin/catenin complex formation by O-linked N-acetylglucosamine transferase is partially independent of its catalytic activity. 26707622 10 49 theme cytoplasmic 1623:1633 arg1 domains 1635:1641 cytoplasmic domains 1623:1641 cytoplasmic domains 1623:1641 Finally, OGT, p120 and E‑cadherin cytoplasmic domains (ECD) were recombinantly expressed in BL21 (DE3) recombinant E. coli cells, and a glutathione S‑transferase (GST) pull‑down assay was performed to assess the interactions among the purified recombinant proteins. 26707622 10 50 theme purified 1824:1831 arg1 proteins 1845:1852 the purified recombinant proteins 1820:1852 the purified recombinant proteins 1820:1852 Finally, OGT, p120 and E‑cadherin cytoplasmic domains (ECD) were recombinantly expressed in BL21 (DE3) recombinant E. coli cells, and a glutathione S‑transferase (GST) pull‑down assay was performed to assess the interactions among the purified recombinant proteins. 26707622 0 51 theme complex 33:39 arg1 formation 41:49 E-cadherin/catenin complex formation 14:49 E-cadherin/catenin complex formation 14:49 Inhibition of E-cadherin/catenin complex formation by O-linked N-acetylglucosamine transferase is partially independent of its catalytic activity. 26707622 13 52 theme cancer 2352:2357 arg1 development 2359:2369 cancer development 2352:2369 cancer development 2352:2369 The present study provided a novel underlying mechanism of the regulation of the interaction between p120 and E‑cadherin, and thus E‑cadherin‑mediated cell‑cell adhesion, which has essential roles in cancer development and progression. 26707622 9 53 theme armadillo 1490:1498 arg1 p120 1511:1514 p120 1511:1514 p120 1511:1514 Immunoblotting showed that OGT bound to the regulatory and armadillo domains of p120, which might interfere with the interaction between p120 and E‑cadherin. 26707622 9 53 theme armadillo 1490:1498 arg1 domains 1500:1506 the regulatory and armadillo domains 1471:1506 the regulatory and armadillo domains 1471:1506 Immunoblotting showed that OGT bound to the regulatory and armadillo domains of p120, which might interfere with the interaction between p120 and E‑cadherin. 26707622 0 54 theme N-acetylglucosamine 63:81 arg1 transferase 83:93 O-linked N-acetylglucosamine transferase 54:93 O-linked N-acetylglucosamine transferase 54:93 Inhibition of E-cadherin/catenin complex formation by O-linked N-acetylglucosamine transferase is partially independent of its catalytic activity. 26707622 13 55 contain has 2329:2331 arg2 roles 2343:2347 essential roles 2333:2347 essential roles 2333:2347 The present study provided a novel underlying mechanism of the regulation of the interaction between p120 and E‑cadherin, and thus E‑cadherin‑mediated cell‑cell adhesion, which has essential roles in cancer development and progression. 26707622 13 55 contain has 2329:2331 arg1 interaction 2233:2243 the interaction 2229:2243 the interaction 2229:2243 The present study provided a novel underlying mechanism of the regulation of the interaction between p120 and E‑cadherin, and thus E‑cadherin‑mediated cell‑cell adhesion, which has essential roles in cancer development and progression. 26707622 3 56 theme proteins 568:575 arg1 majority 545:552 the majority 541:552 the majority of its target proteins 541:575 As O‑GlcNAc transferase (OGT) is able to directly bind to the majority of its target proteins, the present study hypothesized that OGT may additionally regulate the formation of the E‑cadherin/catenin complex independent of its catalytic activity. 26707622 3 57 theme catalytic 711:719 arg1 activity 721:728 its catalytic activity 707:728 its catalytic activity 707:728 As O‑GlcNAc transferase (OGT) is able to directly bind to the majority of its target proteins, the present study hypothesized that OGT may additionally regulate the formation of the E‑cadherin/catenin complex independent of its catalytic activity. 26707622 10 58 theme recombinant 1692:1702 arg1 cells 1712:1716 BL21 (DE3) recombinant E. coli cells 1681:1716 BL21 (DE3) recombinant E. coli cells 1681:1716 Finally, OGT, p120 and E‑cadherin cytoplasmic domains (ECD) were recombinantly expressed in BL21 (DE3) recombinant E. coli cells, and a glutathione S‑transferase (GST) pull‑down assay was performed to assess the interactions among the purified recombinant proteins. 26707622 0 59 theme O-linked 54:61 arg1 transferase 83:93 O-linked N-acetylglucosamine transferase 54:93 O-linked N-acetylglucosamine transferase 54:93 Inhibition of E-cadherin/catenin complex formation by O-linked N-acetylglucosamine transferase is partially independent of its catalytic activity. 26707622 8 60 theme pull‑down 1413:1421 arg1 assays 1423:1428 pull‑down assays 1413:1428 pull‑down assays 1413:1428 To determine the domain of p120 involved in binding to OGT, a series of deletion mutants of p120 were constructed and subjected to protein binding assays by pull‑down assays. 26707622 4 61 theme complex 883:889 arg1 formation 847:855 the formation 843:855 the formation of the E‑cadherin/catenin complex 843:889 To verify this hypothesis, a catalytically inactive OGT mutant was expressed in H1299 cells, and its effects on the formation of the E‑cadherin/catenin complex were assessed. 26707622 13 62 theme cell‑cell 2303:2311 arg1 adhesion 2313:2320 E‑cadherin‑mediated cell‑cell adhesion 2283:2320 E‑cadherin‑mediated cell‑cell adhesion 2283:2320 The present study provided a novel underlying mechanism of the regulation of the interaction between p120 and E‑cadherin, and thus E‑cadherin‑mediated cell‑cell adhesion, which has essential roles in cancer development and progression. 26707622 5 63 theme activity 1060:1067 arg1 independent 1031:1041 independent 1031:1041 independent 1031:1041 A cytoskeleton‑binding protein extraction assay confirmed that OGT inhibited the formation of the E‑cadherin/catenin complex independent of its catalytic activity. 26707622 5 64 theme cytoskeleton‑binding 908:927 arg1 assay 948:952 A cytoskeleton‑binding protein extraction assay 906:952 A cytoskeleton‑binding protein extraction assay 906:952 A cytoskeleton‑binding protein extraction assay confirmed that OGT inhibited the formation of the E‑cadherin/catenin complex independent of its catalytic activity. 26707622 4 65 theme H1299 811:815 arg1 cells 817:821 H1299 cells 811:821 H1299 cells 811:821 To verify this hypothesis, a catalytically inactive OGT mutant was expressed in H1299 cells, and its effects on the formation of the E‑cadherin/catenin complex were assessed. 26707622 3 66 theme E‑cadherin/catenin 665:682 arg1 complex 684:690 the E‑cadherin/catenin complex 661:690 the E‑cadherin/catenin complex independent of its catalytic activity 661:728 As O‑GlcNAc transferase (OGT) is able to directly bind to the majority of its target proteins, the present study hypothesized that OGT may additionally regulate the formation of the E‑cadherin/catenin complex independent of its catalytic activity. 26707622 13 67 theme regulation 2215:2224 arg1 mechanism 2198:2206 a novel underlying mechanism 2179:2206 a novel underlying mechanism of the regulation of the interaction between p120 and E‑cadherin, and thus E‑cadherin‑mediated cell‑cell adhesion, which has essential roles in cancer development and progression 2179:2385 The present study provided a novel underlying mechanism of the regulation of the interaction between p120 and E‑cadherin, and thus E‑cadherin‑mediated cell‑cell adhesion, which has essential roles in cancer development and progression. 26707622 3 68 theme present 582:588 arg1 study 590:594 the present study 578:594 the present study 578:594 As O‑GlcNAc transferase (OGT) is able to directly bind to the majority of its target proteins, the present study hypothesized that OGT may additionally regulate the formation of the E‑cadherin/catenin complex independent of its catalytic activity. 26707622 3 69 theme O‑GlcNAc 486:493 arg1 OGT 508:510 OGT 508:510 OGT 508:510 As O‑GlcNAc transferase (OGT) is able to directly bind to the majority of its target proteins, the present study hypothesized that OGT may additionally regulate the formation of the E‑cadherin/catenin complex independent of its catalytic activity. 26707622 3 69 theme O‑GlcNAc 486:493 arg1 transferase 495:505 O‑GlcNAc transferase 486:505 O‑GlcNAc transferase (OGT) 486:511 As O‑GlcNAc transferase (OGT) is able to directly bind to the majority of its target proteins, the present study hypothesized that OGT may additionally regulate the formation of the E‑cadherin/catenin complex independent of its catalytic activity. 26707622 10 70 theme GST 1752:1754 arg1 assay 1767:1771 a glutathione S‑transferase (GST) pull‑down assay 1723:1771 a glutathione S‑transferase (GST) pull‑down assay 1723:1771 Finally, OGT, p120 and E‑cadherin cytoplasmic domains (ECD) were recombinantly expressed in BL21 (DE3) recombinant E. coli cells, and a glutathione S‑transferase (GST) pull‑down assay was performed to assess the interactions among the purified recombinant proteins. 26707622 5 71 theme E‑cadherin/catenin 1004:1021 arg1 complex 1023:1029 the E‑cadherin/catenin complex 1000:1029 the E‑cadherin/catenin complex 1000:1029 A cytoskeleton‑binding protein extraction assay confirmed that OGT inhibited the formation of the E‑cadherin/catenin complex independent of its catalytic activity. 26707622 5 72 theme extraction 937:946 arg1 assay 948:952 A cytoskeleton‑binding protein extraction assay 906:952 A cytoskeleton‑binding protein extraction assay 906:952 A cytoskeleton‑binding protein extraction assay confirmed that OGT inhibited the formation of the E‑cadherin/catenin complex independent of its catalytic activity. 26707622 5 73 theme protein 929:935 arg1 assay 948:952 A cytoskeleton‑binding protein extraction assay 906:952 A cytoskeleton‑binding protein extraction assay 906:952 A cytoskeleton‑binding protein extraction assay confirmed that OGT inhibited the formation of the E‑cadherin/catenin complex independent of its catalytic activity. 26707622 5 74 theme complex 1023:1029 arg1 formation 987:995 the formation 983:995 the formation of the E‑cadherin/catenin complex independent of its catalytic activity 983:1067 A cytoskeleton‑binding protein extraction assay confirmed that OGT inhibited the formation of the E‑cadherin/catenin complex independent of its catalytic activity. 26707622 11 75 theme dose‑dependent 1969:1982 arg1 manner 1984:1989 a dose‑dependent manner 1967:1989 a dose‑dependent manner 1967:1989 Immunoblotting indicated that maltose‑binding protein (MBP)‑OGT inhibited the binding of His‑p120 to GST‑ECD in a dose‑dependent manner. 26707622 10 76 theme coli 1707:1710 arg1 cells 1712:1716 BL21 (DE3) recombinant E. coli cells 1681:1716 BL21 (DE3) recombinant E. coli cells 1681:1716 Finally, OGT, p120 and E‑cadherin cytoplasmic domains (ECD) were recombinantly expressed in BL21 (DE3) recombinant E. coli cells, and a glutathione S‑transferase (GST) pull‑down assay was performed to assess the interactions among the purified recombinant proteins. 26707622 6 77 theme pull‑down 1110:1118 arg1 assays 1120:1125 co‑immunoprecipitation and pull‑down assays 1083:1125 co‑immunoprecipitation and pull‑down assays 1083:1125 In addition, co‑immunoprecipitation and pull‑down assays were used to evaluate the interaction between OGT and p120. 26707622 13 78 theme novel 2181:2185 arg1 mechanism 2198:2206 a novel underlying mechanism 2179:2206 a novel underlying mechanism of the regulation of the interaction between p120 and E‑cadherin, and thus E‑cadherin‑mediated cell‑cell adhesion, which has essential roles in cancer development and progression 2179:2385 The present study provided a novel underlying mechanism of the regulation of the interaction between p120 and E‑cadherin, and thus E‑cadherin‑mediated cell‑cell adhesion, which has essential roles in cancer development and progression. 26707622 12 79 theme complex 2082:2088 arg1 formation 2046:2054 the formation 2042:2054 the formation of the E‑cadherin/catenin complex 2042:2088 All of these results suggested that OGT inhibited the formation of the E‑cadherin/catenin complex through reducing the interaction between p120 and E‑cadherin. 26707622 10 80 theme E. 1704:1705 arg1 cells 1712:1716 BL21 (DE3) recombinant E. coli cells 1681:1716 BL21 (DE3) recombinant E. coli cells 1681:1716 Finally, OGT, p120 and E‑cadherin cytoplasmic domains (ECD) were recombinantly expressed in BL21 (DE3) recombinant E. coli cells, and a glutathione S‑transferase (GST) pull‑down assay was performed to assess the interactions among the purified recombinant proteins. 26707622 0 81 theme E-cadherin/catenin 14:31 arg1 formation 41:49 E-cadherin/catenin complex formation 14:49 E-cadherin/catenin complex formation 14:49 Inhibition of E-cadherin/catenin complex formation by O-linked N-acetylglucosamine transferase is partially independent of its catalytic activity. 26707622 13 82 theme underlying 2187:2196 arg1 mechanism 2198:2206 a novel underlying mechanism 2179:2206 a novel underlying mechanism of the regulation of the interaction between p120 and E‑cadherin, and thus E‑cadherin‑mediated cell‑cell adhesion, which has essential roles in cancer development and progression 2179:2385 The present study provided a novel underlying mechanism of the regulation of the interaction between p120 and E‑cadherin, and thus E‑cadherin‑mediated cell‑cell adhesion, which has essential roles in cancer development and progression. 27703839 0 0 link O-linked 77:84 arg1 transferase 106:116 O-linked N-acetylglucosamine transferase 77:116 O-linked N-acetylglucosamine transferase 77:116 Formal modeling and analysis of the hexosamine biosynthetic pathway: role of O-linked N-acetylglucosamine transferase in oncogenesis and cancer progression. 27703839 2 1 theme cellular 398:405 arg1 hyper-O-GlcNAcylation 424:444 hyper-O-GlcNAcylation 424:444 hyper-O-GlcNAcylation 424:444 Increased flux of glucose through the Hexosamine Biosynthetic Pathway (HBP) drives increased cellular O-GlcNAcylation (hyper-O-GlcNAcylation) and contributes to cancer progression by regulating key oncogenes. 27703839 2 1 theme cellular 398:405 arg1 O-GlcNAcylation 407:421 increased cellular O-GlcNAcylation 388:421 increased cellular O-GlcNAcylation (hyper-O-GlcNAcylation) 388:445 Increased flux of glucose through the Hexosamine Biosynthetic Pathway (HBP) drives increased cellular O-GlcNAcylation (hyper-O-GlcNAcylation) and contributes to cancer progression by regulating key oncogenes. 27703839 7 2 theme delay 1188:1192 arg1 constraints 1194:1204 delay constraints 1188:1204 delay constraints 1188:1204 We compute delay constraints to reveal important associations between the production and degradation rates of proteins. 27703839 2 3 theme Biosynthetic 354:365 arg1 Pathway 367:373 the Hexosamine Biosynthetic Pathway 339:373 the Hexosamine Biosynthetic Pathway (HBP) 339:379 Increased flux of glucose through the Hexosamine Biosynthetic Pathway (HBP) drives increased cellular O-GlcNAcylation (hyper-O-GlcNAcylation) and contributes to cancer progression by regulating key oncogenes. 27703839 2 3 theme Biosynthetic 354:365 arg1 HBP 376:378 HBP 376:378 HBP 376:378 Increased flux of glucose through the Hexosamine Biosynthetic Pathway (HBP) drives increased cellular O-GlcNAcylation (hyper-O-GlcNAcylation) and contributes to cancer progression by regulating key oncogenes. 27703839 10 4 theme analyses 1642:1649 arg1 Results 1623:1629 Results 1623:1629 Results of network analyses 1623:1649 Results of network analyses also identify a significant cycle that highlights the role of p53-Mdm2 circuit oscillations in cancer recovery and homeostasis. 27703839 1 5 theme cancer 272:277 arg1 cell 279:282 cancer cell growth and invasion 272:302 cancer cell growth and invasion 272:302 The alteration of glucose metabolism, through increased uptake of glucose and glutamine addiction, is essential to cancer cell growth and invasion. 27703839 0 6 theme Formal 0:5 arg1 modeling 7:14 Formal modeling 0:14 Formal modeling 0:14 Formal modeling and analysis of the hexosamine biosynthetic pathway: role of O-linked N-acetylglucosamine transferase in oncogenesis and cancer progression. 27703839 1 7 theme metabolism 183:192 arg1 essential 259:267 essential 259:267 essential 259:267 The alteration of glucose metabolism, through increased uptake of glucose and glutamine addiction, is essential to cancer cell growth and invasion. 27703839 1 7 theme metabolism 183:192 arg1 alteration 161:170 The alteration 157:170 The alteration 157:170 The alteration of glucose metabolism, through increased uptake of glucose and glutamine addiction, is essential to cancer cell growth and invasion. 27703839 11 8 from progression 1868:1878 arg1 loop 1842:1845 the OGT and c-Myc feedback loop 1815:1845 the OGT and c-Myc feedback loop 1815:1845 Together, our findings suggest that the OGT and c-Myc feedback loop is critical in tumor progression, and targeting these mediators may provide a mechanism-based therapeutic approach to regulate hyper-O-GlcNAcylation in human cancer. 27703839 11 8 from progression 1868:1878 arg1 critical 1850:1857 critical 1850:1857 critical 1850:1857 Together, our findings suggest that the OGT and c-Myc feedback loop is critical in tumor progression, and targeting these mediators may provide a mechanism-based therapeutic approach to regulate hyper-O-GlcNAcylation in human cancer. 27703839 4 9 theme Biological 712:721 arg1 Network 734:740 the Biological Regulatory Network 708:740 the Biological Regulatory Network 708:740 Here, we implement a qualitative modeling framework to analyze the role of the Biological Regulatory Network in HBP activation and its potential effects on key oncogenes. 27703839 10 10 theme significant 1667:1677 arg1 cycle 1679:1683 a significant cycle 1665:1683 a significant cycle that highlights the role of p53-Mdm2 circuit oscillations in cancer recovery and homeostasis 1665:1776 Results of network analyses also identify a significant cycle that highlights the role of p53-Mdm2 circuit oscillations in cancer recovery and homeostasis. 27703839 9 11 theme OGT 1542:1544 arg1 Silencing 1525:1533 Silencing 1525:1533 Silencing of the OGT and c-Myc loop 1525:1559 Silencing of the OGT and c-Myc loop decreases glycolytic flux and leads to programmed cell death. 27703839 6 12 theme genetic 1008:1014 arg1 alterations 1016:1026 step-wise genetic alterations 998:1026 step-wise genetic alterations that promote cancer development and invasion due to an increase in glycolytic flux, and reveal critical trajectories involved in cancer progression 998:1174 Using this model, we discover step-wise genetic alterations that promote cancer development and invasion due to an increase in glycolytic flux, and reveal critical trajectories involved in cancer progression. 27703839 8 13 theme c-Myc 1518:1522 arg1 stabilization 1501:1513 the stabilization 1497:1513 the stabilization of c-Myc 1497:1522 O-linked N-acetylglucosamine transferase (OGT), an enzyme used for addition of O-GlcNAc during O-GlcNAcylation, is identified as a key regulator to promote oncogenesis in a feedback mechanism through the stabilization of c-Myc. 27703839 0 14 theme cancer 137:142 arg1 progression 144:154 cancer progression 137:154 cancer progression 137:154 Formal modeling and analysis of the hexosamine biosynthetic pathway: role of O-linked N-acetylglucosamine transferase in oncogenesis and cancer progression. 27703839 1 15 theme glucose 223:229 arg1 uptake 213:218 increased uptake 203:218 increased uptake of glucose and glutamine addiction 203:253 The alteration of glucose metabolism, through increased uptake of glucose and glutamine addiction, is essential to cancer cell growth and invasion. 27703839 8 16 theme N-acetylglucosamine 1306:1324 arg1 OGT 1339:1341 OGT 1339:1341 OGT 1339:1341 O-linked N-acetylglucosamine transferase (OGT), an enzyme used for addition of O-GlcNAc during O-GlcNAcylation, is identified as a key regulator to promote oncogenesis in a feedback mechanism through the stabilization of c-Myc. 27703839 8 16 theme N-acetylglucosamine 1306:1324 arg1 transferase 1326:1336 O-linked N-acetylglucosamine transferase 1297:1336 O-linked N-acetylglucosamine transferase (OGT) 1297:1342 O-linked N-acetylglucosamine transferase (OGT), an enzyme used for addition of O-GlcNAc during O-GlcNAcylation, is identified as a key regulator to promote oncogenesis in a feedback mechanism through the stabilization of c-Myc. 27703839 8 16 theme N-acetylglucosamine 1306:1324 arg1 enzyme 1348:1353 an enzyme 1345:1353 an enzyme used for addition of O-GlcNAc during O-GlcNAcylation 1345:1406 O-linked N-acetylglucosamine transferase (OGT), an enzyme used for addition of O-GlcNAc during O-GlcNAcylation, is identified as a key regulator to promote oncogenesis in a feedback mechanism through the stabilization of c-Myc. 27703839 8 16 theme N-acetylglucosamine 1306:1324 arg1 regulator 1432:1440 a key regulator 1426:1440 a key regulator to promote oncogenesis in a feedback mechanism through the stabilization of c-Myc 1426:1522 O-linked N-acetylglucosamine transferase (OGT), an enzyme used for addition of O-GlcNAc during O-GlcNAcylation, is identified as a key regulator to promote oncogenesis in a feedback mechanism through the stabilization of c-Myc. 27703839 8 17 theme O-GlcNAc 1376:1383 arg1 addition 1364:1371 addition 1364:1371 addition of O-GlcNAc during O-GlcNAcylation 1364:1406 O-linked N-acetylglucosamine transferase (OGT), an enzyme used for addition of O-GlcNAc during O-GlcNAcylation, is identified as a key regulator to promote oncogenesis in a feedback mechanism through the stabilization of c-Myc. 27703839 4 18 theme potential 768:776 arg1 effects 778:784 its potential effects 764:784 its potential effects on key oncogenes 764:801 Here, we implement a qualitative modeling framework to analyze the role of the Biological Regulatory Network in HBP activation and its potential effects on key oncogenes. 27703839 4 19 theme Network 734:740 arg1 effects 778:784 its potential effects 764:784 its potential effects on key oncogenes 764:801 Here, we implement a qualitative modeling framework to analyze the role of the Biological Regulatory Network in HBP activation and its potential effects on key oncogenes. 27703839 4 19 theme Network 734:740 arg1 role 700:703 the role 696:703 the role of the Biological Regulatory Network in HBP activation 696:758 Here, we implement a qualitative modeling framework to analyze the role of the Biological Regulatory Network in HBP activation and its potential effects on key oncogenes. 27703839 5 20 theme Experimental 804:815 arg1 observations 817:828 Experimental observations 804:828 Experimental observations 804:828 Experimental observations are encoded in a temporal language format and model checking is applied to infer the model parameters and qualitative model construction. 27703839 5 21 theme qualitative 936:946 arg1 construction 954:965 qualitative model construction 936:965 qualitative model construction 936:965 Experimental observations are encoded in a temporal language format and model checking is applied to infer the model parameters and qualitative model construction. 27703839 6 22 theme due 1073:1075 arg1 development 1048:1058 cancer development 1041:1058 cancer development 1041:1058 Using this model, we discover step-wise genetic alterations that promote cancer development and invasion due to an increase in glycolytic flux, and reveal critical trajectories involved in cancer progression. 27703839 4 23 theme HBP 745:747 arg1 activation 749:758 HBP activation 745:758 HBP activation 745:758 Here, we implement a qualitative modeling framework to analyze the role of the Biological Regulatory Network in HBP activation and its potential effects on key oncogenes. 27703839 9 24 theme programmed 1600:1609 arg1 death 1616:1620 programmed cell death 1600:1620 programmed cell death 1600:1620 Silencing of the OGT and c-Myc loop decreases glycolytic flux and leads to programmed cell death. 27703839 6 25 from increase 1083:1090 arg1 flux 1106:1109 glycolytic flux 1095:1109 glycolytic flux 1095:1109 Using this model, we discover step-wise genetic alterations that promote cancer development and invasion due to an increase in glycolytic flux, and reveal critical trajectories involved in cancer progression. 27703839 11 26 theme feedback 1833:1840 arg1 loop 1842:1845 the OGT and c-Myc feedback loop 1815:1845 the OGT and c-Myc feedback loop 1815:1845 Together, our findings suggest that the OGT and c-Myc feedback loop is critical in tumor progression, and targeting these mediators may provide a mechanism-based therapeutic approach to regulate hyper-O-GlcNAcylation in human cancer. 27703839 11 26 theme feedback 1833:1840 arg1 critical 1850:1857 critical 1850:1857 critical 1850:1857 Together, our findings suggest that the OGT and c-Myc feedback loop is critical in tumor progression, and targeting these mediators may provide a mechanism-based therapeutic approach to regulate hyper-O-GlcNAcylation in human cancer. 27703839 0 27 theme O-linked 77:84 arg1 transferase 106:116 O-linked N-acetylglucosamine transferase 77:116 O-linked N-acetylglucosamine transferase 77:116 Formal modeling and analysis of the hexosamine biosynthetic pathway: role of O-linked N-acetylglucosamine transferase in oncogenesis and cancer progression. 27703839 6 28 theme cancer 1041:1046 arg1 development 1048:1058 cancer development 1041:1058 cancer development 1041:1058 Using this model, we discover step-wise genetic alterations that promote cancer development and invasion due to an increase in glycolytic flux, and reveal critical trajectories involved in cancer progression. 27703839 8 29 theme key 1428:1430 arg1 transferase 1326:1336 O-linked N-acetylglucosamine transferase 1297:1336 O-linked N-acetylglucosamine transferase (OGT) 1297:1342 O-linked N-acetylglucosamine transferase (OGT), an enzyme used for addition of O-GlcNAc during O-GlcNAcylation, is identified as a key regulator to promote oncogenesis in a feedback mechanism through the stabilization of c-Myc. 27703839 8 29 theme key 1428:1430 arg1 regulator 1432:1440 a key regulator 1426:1440 a key regulator to promote oncogenesis in a feedback mechanism through the stabilization of c-Myc 1426:1522 O-linked N-acetylglucosamine transferase (OGT), an enzyme used for addition of O-GlcNAc during O-GlcNAcylation, is identified as a key regulator to promote oncogenesis in a feedback mechanism through the stabilization of c-Myc. 27703839 11 30 theme human 1999:2003 arg1 cancer 2005:2010 human cancer 1999:2010 human cancer 1999:2010 Together, our findings suggest that the OGT and c-Myc feedback loop is critical in tumor progression, and targeting these mediators may provide a mechanism-based therapeutic approach to regulate hyper-O-GlcNAcylation in human cancer. 27703839 0 31 theme transferase 106:116 arg1 role 69:72 role 69:72 Formal modeling and analysis of the hexosamine biosynthetic pathway: role of O-linked N-acetylglucosamine transferase in oncogenesis and cancer progression. 0:155 Formal modeling and analysis of the hexosamine biosynthetic pathway: role of O-linked N-acetylglucosamine transferase in oncogenesis and cancer progression. 27703839 6 32 theme critical 1123:1130 arg1 trajectories 1132:1143 critical trajectories 1123:1143 critical trajectories involved in cancer progression 1123:1174 Using this model, we discover step-wise genetic alterations that promote cancer development and invasion due to an increase in glycolytic flux, and reveal critical trajectories involved in cancer progression. 27703839 2 33 theme cancer 466:471 arg1 progression 473:483 cancer progression 466:483 cancer progression 466:483 Increased flux of glucose through the Hexosamine Biosynthetic Pathway (HBP) drives increased cellular O-GlcNAcylation (hyper-O-GlcNAcylation) and contributes to cancer progression by regulating key oncogenes. 27703839 10 34 theme p53-Mdm2 1713:1720 arg1 oscillations 1730:1741 p53-Mdm2 circuit oscillations 1713:1741 p53-Mdm2 circuit oscillations 1713:1741 Results of network analyses also identify a significant cycle that highlights the role of p53-Mdm2 circuit oscillations in cancer recovery and homeostasis. 27703839 7 35 theme production 1251:1260 arg1 rates 1278:1282 the production and degradation rates 1247:1282 the production and degradation rates of proteins 1247:1294 We compute delay constraints to reveal important associations between the production and degradation rates of proteins. 27703839 5 36 theme model 876:880 arg1 checking 882:889 model checking 876:889 model checking 876:889 Experimental observations are encoded in a temporal language format and model checking is applied to infer the model parameters and qualitative model construction. 27703839 2 37 theme key 499:501 arg1 oncogenes 503:511 key oncogenes 499:511 key oncogenes 499:511 Increased flux of glucose through the Hexosamine Biosynthetic Pathway (HBP) drives increased cellular O-GlcNAcylation (hyper-O-GlcNAcylation) and contributes to cancer progression by regulating key oncogenes. 27703839 10 38 dep cancer 1746:1751 arg1 recovery 1753:1760 recovery 1753:1760 recovery 1753:1760 Results of network analyses also identify a significant cycle that highlights the role of p53-Mdm2 circuit oscillations in cancer recovery and homeostasis. 27703839 7 39 theme important 1216:1224 arg1 associations 1226:1237 important associations 1216:1237 important associations between the production and degradation rates of proteins 1216:1294 We compute delay constraints to reveal important associations between the production and degradation rates of proteins. 27703839 0 40 theme pathway 60:66 arg1 analysis 20:27 analysis 20:27 analysis 20:27 Formal modeling and analysis of the hexosamine biosynthetic pathway: role of O-linked N-acetylglucosamine transferase in oncogenesis and cancer progression. 27703839 0 40 theme pathway 60:66 arg1 modeling 7:14 Formal modeling 0:14 Formal modeling 0:14 Formal modeling and analysis of the hexosamine biosynthetic pathway: role of O-linked N-acetylglucosamine transferase in oncogenesis and cancer progression. 27703839 2 41 theme Hexosamine 343:352 arg1 Pathway 367:373 the Hexosamine Biosynthetic Pathway 339:373 the Hexosamine Biosynthetic Pathway (HBP) 339:379 Increased flux of glucose through the Hexosamine Biosynthetic Pathway (HBP) drives increased cellular O-GlcNAcylation (hyper-O-GlcNAcylation) and contributes to cancer progression by regulating key oncogenes. 27703839 2 41 theme Hexosamine 343:352 arg1 HBP 376:378 HBP 376:378 HBP 376:378 Increased flux of glucose through the Hexosamine Biosynthetic Pathway (HBP) drives increased cellular O-GlcNAcylation (hyper-O-GlcNAcylation) and contributes to cancer progression by regulating key oncogenes. 27703839 5 42 theme temporal 847:854 arg1 language 856:863 a temporal language 845:863 a temporal language format 845:870 Experimental observations are encoded in a temporal language format and model checking is applied to infer the model parameters and qualitative model construction. 27703839 6 43 theme cancer 1157:1162 arg1 progression 1164:1174 cancer progression 1157:1174 cancer progression 1157:1174 Using this model, we discover step-wise genetic alterations that promote cancer development and invasion due to an increase in glycolytic flux, and reveal critical trajectories involved in cancer progression. 27703839 4 44 theme qualitative 654:664 arg1 framework 675:683 a qualitative modeling framework 652:683 a qualitative modeling framework to analyze the role of the Biological Regulatory Network in HBP activation and its potential effects on key oncogenes 652:801 Here, we implement a qualitative modeling framework to analyze the role of the Biological Regulatory Network in HBP activation and its potential effects on key oncogenes. 27703839 11 45 theme therapeutic 1941:1951 arg1 approach 1953:1960 a mechanism-based therapeutic approach 1923:1960 a mechanism-based therapeutic approach to regulate hyper-O-GlcNAcylation in human cancer 1923:2010 Together, our findings suggest that the OGT and c-Myc feedback loop is critical in tumor progression, and targeting these mediators may provide a mechanism-based therapeutic approach to regulate hyper-O-GlcNAcylation in human cancer. 27703839 10 46 theme network 1634:1640 arg1 analyses 1642:1649 network analyses 1634:1649 network analyses 1634:1649 Results of network analyses also identify a significant cycle that highlights the role of p53-Mdm2 circuit oscillations in cancer recovery and homeostasis. 27703839 1 47 theme glucose 175:181 arg1 metabolism 183:192 glucose metabolism 175:192 glucose metabolism 175:192 The alteration of glucose metabolism, through increased uptake of glucose and glutamine addiction, is essential to cancer cell growth and invasion. 27703839 0 48 theme hexosamine 36:45 arg1 pathway 60:66 the hexosamine biosynthetic pathway 32:66 the hexosamine biosynthetic pathway 32:66 Formal modeling and analysis of the hexosamine biosynthetic pathway: role of O-linked N-acetylglucosamine transferase in oncogenesis and cancer progression. 27703839 10 49 from role 1705:1708 arg1 cancer 1746:1751 cancer recovery and homeostasis 1746:1776 cancer 1746:1751 Results of network analyses also identify a significant cycle that highlights the role of p53-Mdm2 circuit oscillations in cancer recovery and homeostasis. 27703839 10 49 from role 1705:1708 arg1 homeostasis 1766:1776 homeostasis 1766:1776 homeostasis 1766:1776 Results of network analyses also identify a significant cycle that highlights the role of p53-Mdm2 circuit oscillations in cancer recovery and homeostasis. 27703839 4 50 from role 700:703 arg1 oncogenes 793:801 key oncogenes 789:801 key oncogenes 789:801 Here, we implement a qualitative modeling framework to analyze the role of the Biological Regulatory Network in HBP activation and its potential effects on key oncogenes. 27703839 4 50 from role 700:703 arg1 activation 749:758 HBP activation 745:758 HBP activation 745:758 Here, we implement a qualitative modeling framework to analyze the role of the Biological Regulatory Network in HBP activation and its potential effects on key oncogenes. 27703839 5 51 theme model 915:919 arg1 parameters 921:930 the model parameters 911:930 the model parameters 911:930 Experimental observations are encoded in a temporal language format and model checking is applied to infer the model parameters and qualitative model construction. 27703839 2 52 theme Increased 305:313 arg1 flux 315:318 Increased flux 305:318 Increased flux of glucose through the Hexosamine Biosynthetic Pathway (HBP) 305:379 Increased flux of glucose through the Hexosamine Biosynthetic Pathway (HBP) drives increased cellular O-GlcNAcylation (hyper-O-GlcNAcylation) and contributes to cancer progression by regulating key oncogenes. 27703839 1 53 theme increased 203:211 arg1 uptake 213:218 increased uptake 203:218 increased uptake of glucose and glutamine addiction 203:253 The alteration of glucose metabolism, through increased uptake of glucose and glutamine addiction, is essential to cancer cell growth and invasion. 27703839 11 54 theme tumor 1862:1866 arg1 progression 1868:1878 tumor progression 1862:1878 tumor progression 1862:1878 Together, our findings suggest that the OGT and c-Myc feedback loop is critical in tumor progression, and targeting these mediators may provide a mechanism-based therapeutic approach to regulate hyper-O-GlcNAcylation in human cancer. 27703839 6 55 theme step-wise 998:1006 arg1 alterations 1016:1026 step-wise genetic alterations 998:1026 step-wise genetic alterations that promote cancer development and invasion due to an increase in glycolytic flux, and reveal critical trajectories involved in cancer progression 998:1174 Using this model, we discover step-wise genetic alterations that promote cancer development and invasion due to an increase in glycolytic flux, and reveal critical trajectories involved in cancer progression. 27703839 11 56 from critical 1850:1857 arg1 progression 1868:1878 tumor progression 1862:1878 tumor progression 1862:1878 Together, our findings suggest that the OGT and c-Myc feedback loop is critical in tumor progression, and targeting these mediators may provide a mechanism-based therapeutic approach to regulate hyper-O-GlcNAcylation in human cancer. 27703839 8 57 theme O-linked 1297:1304 arg1 OGT 1339:1341 OGT 1339:1341 OGT 1339:1341 O-linked N-acetylglucosamine transferase (OGT), an enzyme used for addition of O-GlcNAc during O-GlcNAcylation, is identified as a key regulator to promote oncogenesis in a feedback mechanism through the stabilization of c-Myc. 27703839 8 57 theme O-linked 1297:1304 arg1 transferase 1326:1336 O-linked N-acetylglucosamine transferase 1297:1336 O-linked N-acetylglucosamine transferase (OGT) 1297:1342 O-linked N-acetylglucosamine transferase (OGT), an enzyme used for addition of O-GlcNAc during O-GlcNAcylation, is identified as a key regulator to promote oncogenesis in a feedback mechanism through the stabilization of c-Myc. 27703839 8 57 theme O-linked 1297:1304 arg1 enzyme 1348:1353 an enzyme 1345:1353 an enzyme used for addition of O-GlcNAc during O-GlcNAcylation 1345:1406 O-linked N-acetylglucosamine transferase (OGT), an enzyme used for addition of O-GlcNAc during O-GlcNAcylation, is identified as a key regulator to promote oncogenesis in a feedback mechanism through the stabilization of c-Myc. 27703839 8 57 theme O-linked 1297:1304 arg1 regulator 1432:1440 a key regulator 1426:1440 a key regulator to promote oncogenesis in a feedback mechanism through the stabilization of c-Myc 1426:1522 O-linked N-acetylglucosamine transferase (OGT), an enzyme used for addition of O-GlcNAc during O-GlcNAcylation, is identified as a key regulator to promote oncogenesis in a feedback mechanism through the stabilization of c-Myc. 27703839 11 58 theme targeting 1885:1893 arg1 mediators 1901:1909 these mediators 1895:1909 targeting these mediators 1885:1909 Together, our findings suggest that the OGT and c-Myc feedback loop is critical in tumor progression, and targeting these mediators may provide a mechanism-based therapeutic approach to regulate hyper-O-GlcNAcylation in human cancer. 27703839 9 59 theme glycolytic 1571:1580 arg1 flux 1582:1585 glycolytic flux 1571:1585 glycolytic flux 1571:1585 Silencing of the OGT and c-Myc loop decreases glycolytic flux and leads to programmed cell death. 27703839 3 60 theme oncogenes 593:601 arg1 activation 573:582 activation 573:582 activation 573:582 However, the association between hyper-O-GlcNAcylation and activation of these oncogenes remains poorly characterized. 27703839 3 60 theme oncogenes 593:601 arg1 hyper-O-GlcNAcylation 547:567 hyper-O-GlcNAcylation 547:567 hyper-O-GlcNAcylation 547:567 However, the association between hyper-O-GlcNAcylation and activation of these oncogenes remains poorly characterized. 27703839 11 61 from hyper-O-GlcNAcylation 1974:1994 arg1 cancer 2005:2010 human cancer 1999:2010 human cancer 1999:2010 Together, our findings suggest that the OGT and c-Myc feedback loop is critical in tumor progression, and targeting these mediators may provide a mechanism-based therapeutic approach to regulate hyper-O-GlcNAcylation in human cancer. 27703839 11 62 theme c-Myc 1827:1831 arg1 loop 1842:1845 the OGT and c-Myc feedback loop 1815:1845 the OGT and c-Myc feedback loop 1815:1845 Together, our findings suggest that the OGT and c-Myc feedback loop is critical in tumor progression, and targeting these mediators may provide a mechanism-based therapeutic approach to regulate hyper-O-GlcNAcylation in human cancer. 27703839 11 62 theme c-Myc 1827:1831 arg1 critical 1850:1857 critical 1850:1857 critical 1850:1857 Together, our findings suggest that the OGT and c-Myc feedback loop is critical in tumor progression, and targeting these mediators may provide a mechanism-based therapeutic approach to regulate hyper-O-GlcNAcylation in human cancer. 27703839 4 63 theme Regulatory 723:732 arg1 Network 734:740 the Biological Regulatory Network 708:740 the Biological Regulatory Network 708:740 Here, we implement a qualitative modeling framework to analyze the role of the Biological Regulatory Network in HBP activation and its potential effects on key oncogenes. 27703839 11 64 theme OGT 1819:1821 arg1 loop 1842:1845 the OGT and c-Myc feedback loop 1815:1845 the OGT and c-Myc feedback loop 1815:1845 Together, our findings suggest that the OGT and c-Myc feedback loop is critical in tumor progression, and targeting these mediators may provide a mechanism-based therapeutic approach to regulate hyper-O-GlcNAcylation in human cancer. 27703839 11 64 theme OGT 1819:1821 arg1 critical 1850:1857 critical 1850:1857 critical 1850:1857 Together, our findings suggest that the OGT and c-Myc feedback loop is critical in tumor progression, and targeting these mediators may provide a mechanism-based therapeutic approach to regulate hyper-O-GlcNAcylation in human cancer. 27703839 7 65 theme proteins 1287:1294 arg1 rates 1278:1282 the production and degradation rates 1247:1282 the production and degradation rates of proteins 1247:1294 We compute delay constraints to reveal important associations between the production and degradation rates of proteins. 27703839 5 66 theme model 948:952 arg1 construction 954:965 qualitative model construction 936:965 qualitative model construction 936:965 Experimental observations are encoded in a temporal language format and model checking is applied to infer the model parameters and qualitative model construction. 27703839 1 67 dep cell 279:282 arg1 invasion 295:302 invasion 295:302 invasion 295:302 The alteration of glucose metabolism, through increased uptake of glucose and glutamine addiction, is essential to cancer cell growth and invasion. 27703839 1 67 dep cell 279:282 arg1 growth 284:289 growth 284:289 growth 284:289 The alteration of glucose metabolism, through increased uptake of glucose and glutamine addiction, is essential to cancer cell growth and invasion. 27703839 0 68 theme N-acetylglucosamine 86:104 arg1 transferase 106:116 O-linked N-acetylglucosamine transferase 77:116 O-linked N-acetylglucosamine transferase 77:116 Formal modeling and analysis of the hexosamine biosynthetic pathway: role of O-linked N-acetylglucosamine transferase in oncogenesis and cancer progression. 27703839 9 69 theme cell 1611:1614 arg1 death 1616:1620 programmed cell death 1600:1620 programmed cell death 1600:1620 Silencing of the OGT and c-Myc loop decreases glycolytic flux and leads to programmed cell death. 27703839 10 70 theme circuit 1722:1728 arg1 oscillations 1730:1741 p53-Mdm2 circuit oscillations 1713:1741 p53-Mdm2 circuit oscillations 1713:1741 Results of network analyses also identify a significant cycle that highlights the role of p53-Mdm2 circuit oscillations in cancer recovery and homeostasis. 27703839 5 71 theme language 856:863 arg1 format 865:870 a temporal language format 845:870 a temporal language format 845:870 Experimental observations are encoded in a temporal language format and model checking is applied to infer the model parameters and qualitative model construction. 27703839 8 72 link O-linked 1297:1304 arg1 OGT 1339:1341 OGT 1339:1341 OGT 1339:1341 O-linked N-acetylglucosamine transferase (OGT), an enzyme used for addition of O-GlcNAc during O-GlcNAcylation, is identified as a key regulator to promote oncogenesis in a feedback mechanism through the stabilization of c-Myc. 27703839 8 72 link O-linked 1297:1304 arg1 transferase 1326:1336 O-linked N-acetylglucosamine transferase 1297:1336 O-linked N-acetylglucosamine transferase (OGT) 1297:1342 O-linked N-acetylglucosamine transferase (OGT), an enzyme used for addition of O-GlcNAc during O-GlcNAcylation, is identified as a key regulator to promote oncogenesis in a feedback mechanism through the stabilization of c-Myc. 27703839 8 72 link O-linked 1297:1304 arg1 enzyme 1348:1353 an enzyme 1345:1353 an enzyme used for addition of O-GlcNAc during O-GlcNAcylation 1345:1406 O-linked N-acetylglucosamine transferase (OGT), an enzyme used for addition of O-GlcNAc during O-GlcNAcylation, is identified as a key regulator to promote oncogenesis in a feedback mechanism through the stabilization of c-Myc. 27703839 8 72 link O-linked 1297:1304 arg1 regulator 1432:1440 a key regulator 1426:1440 a key regulator to promote oncogenesis in a feedback mechanism through the stabilization of c-Myc 1426:1522 O-linked N-acetylglucosamine transferase (OGT), an enzyme used for addition of O-GlcNAc during O-GlcNAcylation, is identified as a key regulator to promote oncogenesis in a feedback mechanism through the stabilization of c-Myc. 27703839 0 73 from role 69:72 arg1 oncogenesis 121:131 oncogenesis 121:131 oncogenesis 121:131 Formal modeling and analysis of the hexosamine biosynthetic pathway: role of O-linked N-acetylglucosamine transferase in oncogenesis and cancer progression. 27703839 0 73 from role 69:72 arg1 progression 144:154 cancer progression 137:154 cancer progression 137:154 Formal modeling and analysis of the hexosamine biosynthetic pathway: role of O-linked N-acetylglucosamine transferase in oncogenesis and cancer progression. 27703839 4 74 from effects 778:784 arg1 oncogenes 793:801 key oncogenes 789:801 key oncogenes 789:801 Here, we implement a qualitative modeling framework to analyze the role of the Biological Regulatory Network in HBP activation and its potential effects on key oncogenes. 27703839 4 74 from effects 778:784 arg1 activation 749:758 HBP activation 745:758 HBP activation 745:758 Here, we implement a qualitative modeling framework to analyze the role of the Biological Regulatory Network in HBP activation and its potential effects on key oncogenes. 27703839 4 75 theme key 789:791 arg1 oncogenes 793:801 key oncogenes 789:801 key oncogenes 789:801 Here, we implement a qualitative modeling framework to analyze the role of the Biological Regulatory Network in HBP activation and its potential effects on key oncogenes. 27703839 6 76 theme glycolytic 1095:1104 arg1 flux 1106:1109 glycolytic flux 1095:1109 glycolytic flux 1095:1109 Using this model, we discover step-wise genetic alterations that promote cancer development and invasion due to an increase in glycolytic flux, and reveal critical trajectories involved in cancer progression. 27703839 10 77 theme oscillations 1730:1741 arg1 role 1705:1708 the role 1701:1708 the role of p53-Mdm2 circuit oscillations in cancer recovery and homeostasis 1701:1776 Results of network analyses also identify a significant cycle that highlights the role of p53-Mdm2 circuit oscillations in cancer recovery and homeostasis. 27703839 7 78 theme degradation 1266:1276 arg1 rates 1278:1282 the production and degradation rates 1247:1282 the production and degradation rates of proteins 1247:1294 We compute delay constraints to reveal important associations between the production and degradation rates of proteins. 27703839 0 79 theme biosynthetic 47:58 arg1 pathway 60:66 the hexosamine biosynthetic pathway 32:66 the hexosamine biosynthetic pathway 32:66 Formal modeling and analysis of the hexosamine biosynthetic pathway: role of O-linked N-acetylglucosamine transferase in oncogenesis and cancer progression. 27703839 8 80 theme feedback 1470:1477 arg1 mechanism 1479:1487 a feedback mechanism 1468:1487 a feedback mechanism 1468:1487 O-linked N-acetylglucosamine transferase (OGT), an enzyme used for addition of O-GlcNAc during O-GlcNAcylation, is identified as a key regulator to promote oncogenesis in a feedback mechanism through the stabilization of c-Myc. 27703839 11 81 theme mechanism-based 1925:1939 arg1 approach 1953:1960 a mechanism-based therapeutic approach 1923:1960 a mechanism-based therapeutic approach to regulate hyper-O-GlcNAcylation in human cancer 1923:2010 Together, our findings suggest that the OGT and c-Myc feedback loop is critical in tumor progression, and targeting these mediators may provide a mechanism-based therapeutic approach to regulate hyper-O-GlcNAcylation in human cancer. 27703839 1 82 dep glucose 223:229 arg1 addiction 245:253 addiction 245:253 addiction 245:253 The alteration of glucose metabolism, through increased uptake of glucose and glutamine addiction, is essential to cancer cell growth and invasion. 27703839 2 83 theme glucose 323:329 arg1 flux 315:318 Increased flux 305:318 Increased flux of glucose through the Hexosamine Biosynthetic Pathway (HBP) 305:379 Increased flux of glucose through the Hexosamine Biosynthetic Pathway (HBP) drives increased cellular O-GlcNAcylation (hyper-O-GlcNAcylation) and contributes to cancer progression by regulating key oncogenes. 27703839 1 84 theme glutamine 235:243 arg1 uptake 213:218 increased uptake 203:218 increased uptake of glucose and glutamine addiction 203:253 The alteration of glucose metabolism, through increased uptake of glucose and glutamine addiction, is essential to cancer cell growth and invasion. 27703839 9 85 theme c-Myc 1550:1554 arg1 Silencing 1525:1533 Silencing 1525:1533 Silencing of the OGT and c-Myc loop 1525:1559 Silencing of the OGT and c-Myc loop decreases glycolytic flux and leads to programmed cell death. 27703839 0 86 dep modeling 7:14 arg1 role 69:72 role 69:72 Formal modeling and analysis of the hexosamine biosynthetic pathway: role of O-linked N-acetylglucosamine transferase in oncogenesis and cancer progression. 0:155 Formal modeling and analysis of the hexosamine biosynthetic pathway: role of O-linked N-acetylglucosamine transferase in oncogenesis and cancer progression. 27703839 2 87 theme increased 388:396 arg1 hyper-O-GlcNAcylation 424:444 hyper-O-GlcNAcylation 424:444 hyper-O-GlcNAcylation 424:444 Increased flux of glucose through the Hexosamine Biosynthetic Pathway (HBP) drives increased cellular O-GlcNAcylation (hyper-O-GlcNAcylation) and contributes to cancer progression by regulating key oncogenes. 27703839 2 87 theme increased 388:396 arg1 O-GlcNAcylation 407:421 increased cellular O-GlcNAcylation 388:421 increased cellular O-GlcNAcylation (hyper-O-GlcNAcylation) 388:445 Increased flux of glucose through the Hexosamine Biosynthetic Pathway (HBP) drives increased cellular O-GlcNAcylation (hyper-O-GlcNAcylation) and contributes to cancer progression by regulating key oncogenes. 27703839 4 88 theme modeling 666:673 arg1 framework 675:683 a qualitative modeling framework 652:683 a qualitative modeling framework to analyze the role of the Biological Regulatory Network in HBP activation and its potential effects on key oncogenes 652:801 Here, we implement a qualitative modeling framework to analyze the role of the Biological Regulatory Network in HBP activation and its potential effects on key oncogenes. 27703839 9 89 dep OGT 1542:1544 arg1 loop 1556:1559 loop 1556:1559 loop 1556:1559 Silencing of the OGT and c-Myc loop decreases glycolytic flux and leads to programmed cell death. 27703839 9 89 dep OGT 1542:1544 arg1 the 1538:1540 the 1538:1540 the 1538:1540 Silencing of the OGT and c-Myc loop decreases glycolytic flux and leads to programmed cell death. 26688390 3 0 theme structures 840:849 arg1 glycans 909:915 methylfucose-containing glycans 885:915 methylfucose-containing glycans 885:915 We used MALDI-TOF-MS and LC-MS/MS to analyse the repertoire of N- and O-linked glycans released from Heligmosomoides polygyrus excretory-secretory products by PNGase A and F, β-elimination and hydrazinolysis revealing a broad range of structures including novel methylhexose- and methylfucose-containing glycans. 26688390 3 0 theme structures 840:849 arg1 methylhexose- 867:879 novel methylhexose- 861:879 novel methylhexose- 861:879 We used MALDI-TOF-MS and LC-MS/MS to analyse the repertoire of N- and O-linked glycans released from Heligmosomoides polygyrus excretory-secretory products by PNGase A and F, β-elimination and hydrazinolysis revealing a broad range of structures including novel methylhexose- and methylfucose-containing glycans. 26688390 3 0 theme structures 840:849 arg1 range 831:835 a broad range 823:835 a broad range of structures including novel methylhexose- and methylfucose-containing glycans 823:915 We used MALDI-TOF-MS and LC-MS/MS to analyse the repertoire of N- and O-linked glycans released from Heligmosomoides polygyrus excretory-secretory products by PNGase A and F, β-elimination and hydrazinolysis revealing a broad range of structures including novel methylhexose- and methylfucose-containing glycans. 26688390 2 1 contain contain 522:528 arg1 products 483:490 the excretory-secretory products 459:490 the excretory-secretory products (termed HES) of this parasite 459:520 Glycoproteins secreted by the intestinal nematode Heligmosomoides polygyrus are of particular interest as the excretory-secretory products (termed HES) of this parasite contain both heat-labile and heat-stable components with immunomodulatory effects. 26688390 2 1 contain contain 522:528 arg2 components 563:572 both heat-labile and heat-stable components 530:572 both heat-labile and heat-stable components 530:572 Glycoproteins secreted by the intestinal nematode Heligmosomoides polygyrus are of particular interest as the excretory-secretory products (termed HES) of this parasite contain both heat-labile and heat-stable components with immunomodulatory effects. 26688390 2 1 contain contain 522:528 arg1 HES 500:502 termed HES 493:502 termed HES 493:502 Glycoproteins secreted by the intestinal nematode Heligmosomoides polygyrus are of particular interest as the excretory-secretory products (termed HES) of this parasite contain both heat-labile and heat-stable components with immunomodulatory effects. 26688390 1 2 theme specific 329:336 arg1 immunity 343:350 specific host immunity 329:350 specific host immunity 329:350 Glycan molecules from helminth parasites have been associated with diverse biological functions ranging from interactions with neighbouring host cell populations to down-modulation of specific host immunity. 26688390 4 3 theme designated 998:1007 arg1 A 1017:1017 previously designated Glycans A 987:1017 previously designated Glycans A 987:1017 Monoclonal antibodies to two immunodominant glycans of H. polygyrus, previously designated Glycans A and B, were found to react by glycan array analysis to a methyl-hexose-rich fraction and to a sulphated LacDiNAc (LDN; GalNAcβ1-4GlcNAc) structure, respectively. 26688390 4 3 theme designated 998:1007 arg1 glycans 962:968 two immunodominant glycans 943:968 two immunodominant glycans of H. polygyrus 943:984 Monoclonal antibodies to two immunodominant glycans of H. polygyrus, previously designated Glycans A and B, were found to react by glycan array analysis to a methyl-hexose-rich fraction and to a sulphated LacDiNAc (LDN; GalNAcβ1-4GlcNAc) structure, respectively. 26688390 1 4 theme diverse 212:218 arg1 functions 231:239 diverse biological functions 212:239 diverse biological functions ranging from interactions with neighbouring host cell populations to down-modulation of specific host immunity 212:350 Glycan molecules from helminth parasites have been associated with diverse biological functions ranging from interactions with neighbouring host cell populations to down-modulation of specific host immunity. 26688390 4 5 theme array 1056:1060 arg1 analysis 1062:1069 glycan array analysis 1049:1069 glycan array analysis 1049:1069 Monoclonal antibodies to two immunodominant glycans of H. polygyrus, previously designated Glycans A and B, were found to react by glycan array analysis to a methyl-hexose-rich fraction and to a sulphated LacDiNAc (LDN; GalNAcβ1-4GlcNAc) structure, respectively. 26688390 3 6 theme novel 861:865 arg1 methylhexose- 867:879 novel methylhexose- 861:879 novel methylhexose- 861:879 We used MALDI-TOF-MS and LC-MS/MS to analyse the repertoire of N- and O-linked glycans released from Heligmosomoides polygyrus excretory-secretory products by PNGase A and F, β-elimination and hydrazinolysis revealing a broad range of structures including novel methylhexose- and methylfucose-containing glycans. 26688390 5 7 gly glycoprotein 1231:1242 arg1 glycoprotein 1231:1242 a major glycoprotein 1223:1242 a major glycoprotein in Heligmosomoides polygyrus excretory-secretory products, VAL-2, which contains many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation 1223:1681 We also analysed the glycan repertoire of a major glycoprotein in Heligmosomoides polygyrus excretory-secretory products, VAL-2, which contains many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation. 26688390 1 8 theme immunity 343:350 arg1 down-modulation 310:324 down-modulation 310:324 down-modulation of specific host immunity 310:350 Glycan molecules from helminth parasites have been associated with diverse biological functions ranging from interactions with neighbouring host cell populations to down-modulation of specific host immunity. 26688390 3 9 theme glycans 684:690 arg1 N- 668:669 N- 668:669 N- 668:669 We used MALDI-TOF-MS and LC-MS/MS to analyse the repertoire of N- and O-linked glycans released from Heligmosomoides polygyrus excretory-secretory products by PNGase A and F, β-elimination and hydrazinolysis revealing a broad range of structures including novel methylhexose- and methylfucose-containing glycans. 26688390 3 9 theme glycans 684:690 arg1 glycans 684:690 O-linked glycans 675:690 O-linked glycans released from Heligmosomoides polygyrus 675:730 We used MALDI-TOF-MS and LC-MS/MS to analyse the repertoire of N- and O-linked glycans released from Heligmosomoides polygyrus excretory-secretory products by PNGase A and F, β-elimination and hydrazinolysis revealing a broad range of structures including novel methylhexose- and methylfucose-containing glycans. 26688390 3 9 theme glycans 684:690 arg1 repertoire 654:663 the repertoire 650:663 the repertoire of N- and O-linked glycans released from Heligmosomoides polygyrus excretory-secretory products 650:759 We used MALDI-TOF-MS and LC-MS/MS to analyse the repertoire of N- and O-linked glycans released from Heligmosomoides polygyrus excretory-secretory products by PNGase A and F, β-elimination and hydrazinolysis revealing a broad range of structures including novel methylhexose- and methylfucose-containing glycans. 26688390 6 10 theme glycoconjugates 1777:1791 arg1 range 1758:1762 a diverse range 1748:1762 a diverse range of antigenic glycoconjugates 1748:1791 Taken together, these studies reveal that H. polygyrus secretes a diverse range of antigenic glycoconjugates, and provides a framework to explore the biological and immunomodulatory roles they may play within the mammalian host. 26688390 0 11 from polygyrus 134:142 arg1 glycoproteins 75:87 secreted immunodominant glycoproteins 51:87 secreted immunodominant glycoproteins from the intestinal nematode Heligmosomoides polygyrus 51:142 Novel O-linked methylated glycan antigens decorate secreted immunodominant glycoproteins from the intestinal nematode Heligmosomoides polygyrus. 26688390 5 12 from products 1405:1412 arg1 present 1348:1354 present 1348:1354 present 1348:1354 We also analysed the glycan repertoire of a major glycoprotein in Heligmosomoides polygyrus excretory-secretory products, VAL-2, which contains many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation. 26688390 1 13 theme helminth 167:174 arg1 parasites 176:184 helminth parasites 167:184 helminth parasites 167:184 Glycan molecules from helminth parasites have been associated with diverse biological functions ranging from interactions with neighbouring host cell populations to down-modulation of specific host immunity. 26688390 6 14 theme immunomodulatory 1849:1864 arg1 roles 1866:1870 the biological and immunomodulatory roles 1830:1870 the biological and immunomodulatory roles they may play within the mammalian host 1830:1910 Taken together, these studies reveal that H. polygyrus secretes a diverse range of antigenic glycoconjugates, and provides a framework to explore the biological and immunomodulatory roles they may play within the mammalian host. 26688390 5 15 theme Heligmosomoides 1247:1261 arg1 polygyrus 1263:1271 Heligmosomoides polygyrus excretory-secretory products, VAL-2, which contains many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation 1247:1681 polygyrus 1263:1271 We also analysed the glycan repertoire of a major glycoprotein in Heligmosomoides polygyrus excretory-secretory products, VAL-2, which contains many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation. 26688390 5 15 theme Heligmosomoides 1247:1261 arg1 VAL-2 1303:1307 VAL-2 1303:1307 VAL-2 1303:1307 We also analysed the glycan repertoire of a major glycoprotein in Heligmosomoides polygyrus excretory-secretory products, VAL-2, which contains many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation. 26688390 6 16 theme diverse 1750:1756 arg1 range 1758:1762 a diverse range 1748:1762 a diverse range of antigenic glycoconjugates 1748:1791 Taken together, these studies reveal that H. polygyrus secretes a diverse range of antigenic glycoconjugates, and provides a framework to explore the biological and immunomodulatory roles they may play within the mammalian host. 26688390 2 17 theme immunomodulatory 579:594 arg1 effects 596:602 immunomodulatory effects 579:602 immunomodulatory effects 579:602 Glycoproteins secreted by the intestinal nematode Heligmosomoides polygyrus are of particular interest as the excretory-secretory products (termed HES) of this parasite contain both heat-labile and heat-stable components with immunomodulatory effects. 26688390 5 18 theme excretory-secretory 1273:1291 arg1 products 1293:1300 excretory-secretory products 1273:1300 excretory-secretory products 1273:1300 We also analysed the glycan repertoire of a major glycoprotein in Heligmosomoides polygyrus excretory-secretory products, VAL-2, which contains many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation. 26688390 4 19 theme methyl-hexose-rich 1076:1093 arg1 fraction 1095:1102 a methyl-hexose-rich fraction 1074:1102 a methyl-hexose-rich fraction 1074:1102 Monoclonal antibodies to two immunodominant glycans of H. polygyrus, previously designated Glycans A and B, were found to react by glycan array analysis to a methyl-hexose-rich fraction and to a sulphated LacDiNAc (LDN; GalNAcβ1-4GlcNAc) structure, respectively. 26688390 0 20 theme nematode 109:116 arg1 polygyrus 134:142 the intestinal nematode Heligmosomoides polygyrus 94:142 the intestinal nematode Heligmosomoides polygyrus 94:142 Novel O-linked methylated glycan antigens decorate secreted immunodominant glycoproteins from the intestinal nematode Heligmosomoides polygyrus. 26688390 1 21 from parasites 176:184 arg1 molecules 152:160 Glycan molecules 145:160 Glycan molecules from helminth parasites 145:184 Glycan molecules from helminth parasites have been associated with diverse biological functions ranging from interactions with neighbouring host cell populations to down-modulation of specific host immunity. 26688390 5 22 theme polygyrus 1375:1383 arg1 products 1405:1412 Heligmosomoides polygyrus excretory-secretory products 1359:1412 Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation 1359:1681 We also analysed the glycan repertoire of a major glycoprotein in Heligmosomoides polygyrus excretory-secretory products, VAL-2, which contains many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation. 26688390 5 23 theme glycoprotein 1231:1242 arg1 glycoprotein 1231:1242 a major glycoprotein 1223:1242 a major glycoprotein in Heligmosomoides polygyrus excretory-secretory products, VAL-2, which contains many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation 1223:1681 We also analysed the glycan repertoire of a major glycoprotein in Heligmosomoides polygyrus excretory-secretory products, VAL-2, which contains many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation. 26688390 5 23 theme glycoprotein 1231:1242 arg1 repertoire 1209:1218 the glycan repertoire 1198:1218 the glycan repertoire of a major glycoprotein in Heligmosomoides polygyrus excretory-secretory products, VAL-2, which contains many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation 1198:1681 We also analysed the glycan repertoire of a major glycoprotein in Heligmosomoides polygyrus excretory-secretory products, VAL-2, which contains many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation. 26688390 5 24 theme allergic 1656:1663 arg1 inflammation 1670:1681 allergic lung inflammation 1656:1681 allergic lung inflammation 1656:1681 We also analysed the glycan repertoire of a major glycoprotein in Heligmosomoides polygyrus excretory-secretory products, VAL-2, which contains many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation. 26688390 2 25 theme excretory-secretory 463:481 arg1 products 483:490 the excretory-secretory products 459:490 the excretory-secretory products (termed HES) of this parasite 459:520 Glycoproteins secreted by the intestinal nematode Heligmosomoides polygyrus are of particular interest as the excretory-secretory products (termed HES) of this parasite contain both heat-labile and heat-stable components with immunomodulatory effects. 26688390 2 25 theme excretory-secretory 463:481 arg1 HES 500:502 termed HES 493:502 termed HES 493:502 Glycoproteins secreted by the intestinal nematode Heligmosomoides polygyrus are of particular interest as the excretory-secretory products (termed HES) of this parasite contain both heat-labile and heat-stable components with immunomodulatory effects. 26688390 0 26 theme Novel 0:4 arg1 antigens 33:40 Novel O-linked methylated glycan antigens 0:40 Novel O-linked methylated glycan antigens 0:40 Novel O-linked methylated glycan antigens decorate secreted immunodominant glycoproteins from the intestinal nematode Heligmosomoides polygyrus. 26688390 1 27 theme host 338:341 arg1 immunity 343:350 specific host immunity 329:350 specific host immunity 329:350 Glycan molecules from helminth parasites have been associated with diverse biological functions ranging from interactions with neighbouring host cell populations to down-modulation of specific host immunity. 26688390 2 28 theme parasite 513:520 arg1 products 483:490 the excretory-secretory products 459:490 the excretory-secretory products (termed HES) of this parasite 459:520 Glycoproteins secreted by the intestinal nematode Heligmosomoides polygyrus are of particular interest as the excretory-secretory products (termed HES) of this parasite contain both heat-labile and heat-stable components with immunomodulatory effects. 26688390 2 28 theme parasite 513:520 arg1 HES 500:502 termed HES 493:502 termed HES 493:502 Glycoproteins secreted by the intestinal nematode Heligmosomoides polygyrus are of particular interest as the excretory-secretory products (termed HES) of this parasite contain both heat-labile and heat-stable components with immunomodulatory effects. 26688390 0 29 theme methylated 15:24 arg1 antigens 33:40 Novel O-linked methylated glycan antigens 0:40 Novel O-linked methylated glycan antigens 0:40 Novel O-linked methylated glycan antigens decorate secreted immunodominant glycoproteins from the intestinal nematode Heligmosomoides polygyrus. 26688390 5 30 theme glycan 1330:1335 arg1 structures 1337:1346 many glycan structures 1325:1346 many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation 1325:1681 We also analysed the glycan repertoire of a major glycoprotein in Heligmosomoides polygyrus excretory-secretory products, VAL-2, which contains many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation. 26688390 3 31 link O-linked 675:682 arg1 glycans 684:690 O-linked glycans 675:690 O-linked glycans released from Heligmosomoides polygyrus 675:730 We used MALDI-TOF-MS and LC-MS/MS to analyse the repertoire of N- and O-linked glycans released from Heligmosomoides polygyrus excretory-secretory products by PNGase A and F, β-elimination and hydrazinolysis revealing a broad range of structures including novel methylhexose- and methylfucose-containing glycans. 26688390 5 32 dep polygyrus 1263:1271 arg1 products 1293:1300 excretory-secretory products 1273:1300 excretory-secretory products 1273:1300 We also analysed the glycan repertoire of a major glycoprotein in Heligmosomoides polygyrus excretory-secretory products, VAL-2, which contains many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation. 26688390 4 33 theme H. 973:974 arg1 B 1023:1023 B 1023:1023 B 1023:1023 Monoclonal antibodies to two immunodominant glycans of H. polygyrus, previously designated Glycans A and B, were found to react by glycan array analysis to a methyl-hexose-rich fraction and to a sulphated LacDiNAc (LDN; GalNAcβ1-4GlcNAc) structure, respectively. 26688390 4 33 theme H. 973:974 arg1 A 1017:1017 previously designated Glycans A 987:1017 previously designated Glycans A 987:1017 Monoclonal antibodies to two immunodominant glycans of H. polygyrus, previously designated Glycans A and B, were found to react by glycan array analysis to a methyl-hexose-rich fraction and to a sulphated LacDiNAc (LDN; GalNAcβ1-4GlcNAc) structure, respectively. 26688390 4 33 theme H. 973:974 arg1 glycans 962:968 two immunodominant glycans 943:968 two immunodominant glycans of H. polygyrus 943:984 Monoclonal antibodies to two immunodominant glycans of H. polygyrus, previously designated Glycans A and B, were found to react by glycan array analysis to a methyl-hexose-rich fraction and to a sulphated LacDiNAc (LDN; GalNAcβ1-4GlcNAc) structure, respectively. 26688390 3 34 theme PNGase 764:769 arg1 A 771:771 PNGase A 764:771 PNGase A 764:771 We used MALDI-TOF-MS and LC-MS/MS to analyse the repertoire of N- and O-linked glycans released from Heligmosomoides polygyrus excretory-secretory products by PNGase A and F, β-elimination and hydrazinolysis revealing a broad range of structures including novel methylhexose- and methylfucose-containing glycans. 26688390 5 35 theme polygyrus 1567:1575 arg1 products 1597:1604 Heligmosomoides polygyrus excretory-secretory products 1551:1604 Heligmosomoides polygyrus excretory-secretory products 1551:1604 We also analysed the glycan repertoire of a major glycoprotein in Heligmosomoides polygyrus excretory-secretory products, VAL-2, which contains many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation. 26688390 0 36 theme secreted 51:58 arg1 glycoproteins 75:87 secreted immunodominant glycoproteins 51:87 secreted immunodominant glycoproteins from the intestinal nematode Heligmosomoides polygyrus 51:142 Novel O-linked methylated glycan antigens decorate secreted immunodominant glycoproteins from the intestinal nematode Heligmosomoides polygyrus. 26688390 3 37 used used 608:611 arg2 We 605:606 We 605:606 We 605:606 We used MALDI-TOF-MS and LC-MS/MS to analyse the repertoire of N- and O-linked glycans released from Heligmosomoides polygyrus excretory-secretory products by PNGase A and F, β-elimination and hydrazinolysis revealing a broad range of structures including novel methylhexose- and methylfucose-containing glycans. 26688390 5 38 theme products 1597:1604 arg1 properties 1537:1546 the heat-stable immunomodulatory properties 1504:1546 the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products 1504:1604 We also analysed the glycan repertoire of a major glycoprotein in Heligmosomoides polygyrus excretory-secretory products, VAL-2, which contains many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation. 26688390 2 39 theme Heligmosomoides 403:417 arg1 polygyrus 419:427 the intestinal nematode Heligmosomoides polygyrus 379:427 the intestinal nematode Heligmosomoides polygyrus 379:427 Glycoproteins secreted by the intestinal nematode Heligmosomoides polygyrus are of particular interest as the excretory-secretory products (termed HES) of this parasite contain both heat-labile and heat-stable components with immunomodulatory effects. 26688390 5 40 theme excretory-secretory 1385:1403 arg1 products 1405:1412 Heligmosomoides polygyrus excretory-secretory products 1359:1412 Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation 1359:1681 We also analysed the glycan repertoire of a major glycoprotein in Heligmosomoides polygyrus excretory-secretory products, VAL-2, which contains many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation. 26688390 5 41 theme immunomodulatory 1520:1535 arg1 properties 1537:1546 the heat-stable immunomodulatory properties 1504:1546 the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products 1504:1604 We also analysed the glycan repertoire of a major glycoprotein in Heligmosomoides polygyrus excretory-secretory products, VAL-2, which contains many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation. 26688390 1 42 theme cell 290:293 arg1 populations 295:305 neighbouring host cell populations 272:305 neighbouring host cell populations 272:305 Glycan molecules from helminth parasites have been associated with diverse biological functions ranging from interactions with neighbouring host cell populations to down-modulation of specific host immunity. 26688390 3 43 theme broad 825:829 arg1 glycans 909:915 methylfucose-containing glycans 885:915 methylfucose-containing glycans 885:915 We used MALDI-TOF-MS and LC-MS/MS to analyse the repertoire of N- and O-linked glycans released from Heligmosomoides polygyrus excretory-secretory products by PNGase A and F, β-elimination and hydrazinolysis revealing a broad range of structures including novel methylhexose- and methylfucose-containing glycans. 26688390 3 43 theme broad 825:829 arg1 methylhexose- 867:879 novel methylhexose- 861:879 novel methylhexose- 861:879 We used MALDI-TOF-MS and LC-MS/MS to analyse the repertoire of N- and O-linked glycans released from Heligmosomoides polygyrus excretory-secretory products by PNGase A and F, β-elimination and hydrazinolysis revealing a broad range of structures including novel methylhexose- and methylfucose-containing glycans. 26688390 3 43 theme broad 825:829 arg1 range 831:835 a broad range 823:835 a broad range of structures including novel methylhexose- and methylfucose-containing glycans 823:915 We used MALDI-TOF-MS and LC-MS/MS to analyse the repertoire of N- and O-linked glycans released from Heligmosomoides polygyrus excretory-secretory products by PNGase A and F, β-elimination and hydrazinolysis revealing a broad range of structures including novel methylhexose- and methylfucose-containing glycans. 26688390 2 44 theme particular 436:445 arg1 interest 447:454 particular interest 436:454 particular interest 436:454 Glycoproteins secreted by the intestinal nematode Heligmosomoides polygyrus are of particular interest as the excretory-secretory products (termed HES) of this parasite contain both heat-labile and heat-stable components with immunomodulatory effects. 26688390 5 45 theme present 1348:1354 arg1 structures 1337:1346 many glycan structures 1325:1346 many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation 1325:1681 We also analysed the glycan repertoire of a major glycoprotein in Heligmosomoides polygyrus excretory-secretory products, VAL-2, which contains many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation. 26688390 4 46 dep LDN 1133:1135 arg1 GalNAcβ1-4GlcNAc 1138:1153 GalNAcβ1-4GlcNAc 1138:1153 LDN; GalNAcβ1-4GlcNAc 1133:1153 Monoclonal antibodies to two immunodominant glycans of H. polygyrus, previously designated Glycans A and B, were found to react by glycan array analysis to a methyl-hexose-rich fraction and to a sulphated LacDiNAc (LDN; GalNAcβ1-4GlcNAc) structure, respectively. 26688390 5 47 theme Heligmosomoides 1359:1373 arg1 polygyrus 1375:1383 Heligmosomoides polygyrus 1359:1383 Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation 1359:1681 We also analysed the glycan repertoire of a major glycoprotein in Heligmosomoides polygyrus excretory-secretory products, VAL-2, which contains many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation. 26688390 3 48 theme N- 668:669 arg1 N- 668:669 N- 668:669 N- 668:669 We used MALDI-TOF-MS and LC-MS/MS to analyse the repertoire of N- and O-linked glycans released from Heligmosomoides polygyrus excretory-secretory products by PNGase A and F, β-elimination and hydrazinolysis revealing a broad range of structures including novel methylhexose- and methylfucose-containing glycans. 26688390 3 48 theme N- 668:669 arg1 glycans 684:690 O-linked glycans 675:690 O-linked glycans released from Heligmosomoides polygyrus 675:730 We used MALDI-TOF-MS and LC-MS/MS to analyse the repertoire of N- and O-linked glycans released from Heligmosomoides polygyrus excretory-secretory products by PNGase A and F, β-elimination and hydrazinolysis revealing a broad range of structures including novel methylhexose- and methylfucose-containing glycans. 26688390 3 48 theme N- 668:669 arg1 repertoire 654:663 the repertoire 650:663 the repertoire of N- and O-linked glycans released from Heligmosomoides polygyrus excretory-secretory products 650:759 We used MALDI-TOF-MS and LC-MS/MS to analyse the repertoire of N- and O-linked glycans released from Heligmosomoides polygyrus excretory-secretory products by PNGase A and F, β-elimination and hydrazinolysis revealing a broad range of structures including novel methylhexose- and methylfucose-containing glycans. 26688390 0 49 link O-linked 6:13 arg1 antigens 33:40 Novel O-linked methylated glycan antigens 0:40 Novel O-linked methylated glycan antigens 0:40 Novel O-linked methylated glycan antigens decorate secreted immunodominant glycoproteins from the intestinal nematode Heligmosomoides polygyrus. 26688390 5 50 theme VAL-2 1639:1643 arg1 inability 1626:1634 the inability 1622:1634 the inability of VAL-2 to inhibit allergic lung inflammation 1622:1681 We also analysed the glycan repertoire of a major glycoprotein in Heligmosomoides polygyrus excretory-secretory products, VAL-2, which contains many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation. 26688390 5 51 from polygyrus 1263:1271 arg1 glycoprotein 1231:1242 a major glycoprotein 1223:1242 a major glycoprotein in Heligmosomoides polygyrus excretory-secretory products, VAL-2, which contains many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation 1223:1681 We also analysed the glycan repertoire of a major glycoprotein in Heligmosomoides polygyrus excretory-secretory products, VAL-2, which contains many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation. 26688390 5 51 from polygyrus 1263:1271 arg1 repertoire 1209:1218 the glycan repertoire 1198:1218 the glycan repertoire of a major glycoprotein in Heligmosomoides polygyrus excretory-secretory products, VAL-2, which contains many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation 1198:1681 We also analysed the glycan repertoire of a major glycoprotein in Heligmosomoides polygyrus excretory-secretory products, VAL-2, which contains many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation. 26688390 6 52 dep H. 1726:1727 arg1 polygyrus 1729:1737 H. polygyrus 1726:1737 H. polygyrus 1726:1737 Taken together, these studies reveal that H. polygyrus secretes a diverse range of antigenic glycoconjugates, and provides a framework to explore the biological and immunomodulatory roles they may play within the mammalian host. 26688390 2 53 theme intestinal 383:392 arg1 polygyrus 419:427 the intestinal nematode Heligmosomoides polygyrus 379:427 the intestinal nematode Heligmosomoides polygyrus 379:427 Glycoproteins secreted by the intestinal nematode Heligmosomoides polygyrus are of particular interest as the excretory-secretory products (termed HES) of this parasite contain both heat-labile and heat-stable components with immunomodulatory effects. 26688390 1 54 theme biological 220:229 arg1 functions 231:239 diverse biological functions 212:239 diverse biological functions ranging from interactions with neighbouring host cell populations to down-modulation of specific host immunity 212:350 Glycan molecules from helminth parasites have been associated with diverse biological functions ranging from interactions with neighbouring host cell populations to down-modulation of specific host immunity. 26688390 6 55 dep roles 1866:1870 arg1 play 1881:1884 play 1881:1884 may play within the mammalian host 1877:1910 Taken together, these studies reveal that H. polygyrus secretes a diverse range of antigenic glycoconjugates, and provides a framework to explore the biological and immunomodulatory roles they may play within the mammalian host. 26688390 4 56 theme Glycans 1009:1015 arg1 A 1017:1017 previously designated Glycans A 987:1017 previously designated Glycans A 987:1017 Monoclonal antibodies to two immunodominant glycans of H. polygyrus, previously designated Glycans A and B, were found to react by glycan array analysis to a methyl-hexose-rich fraction and to a sulphated LacDiNAc (LDN; GalNAcβ1-4GlcNAc) structure, respectively. 26688390 4 56 theme Glycans 1009:1015 arg1 glycans 962:968 two immunodominant glycans 943:968 two immunodominant glycans of H. polygyrus 943:984 Monoclonal antibodies to two immunodominant glycans of H. polygyrus, previously designated Glycans A and B, were found to react by glycan array analysis to a methyl-hexose-rich fraction and to a sulphated LacDiNAc (LDN; GalNAcβ1-4GlcNAc) structure, respectively. 26688390 5 57 dep A. 1431:1432 arg1 found 1450:1454 found 1450:1454 was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation 1446:1681 We also analysed the glycan repertoire of a major glycoprotein in Heligmosomoides polygyrus excretory-secretory products, VAL-2, which contains many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation. 26688390 3 58 theme methylfucose-containing 885:907 arg1 glycans 909:915 methylfucose-containing glycans 885:915 methylfucose-containing glycans 885:915 We used MALDI-TOF-MS and LC-MS/MS to analyse the repertoire of N- and O-linked glycans released from Heligmosomoides polygyrus excretory-secretory products by PNGase A and F, β-elimination and hydrazinolysis revealing a broad range of structures including novel methylhexose- and methylfucose-containing glycans. 26688390 4 59 theme LacDiNAc 1123:1130 arg1 structure 1156:1164 a sulphated LacDiNAc (LDN; GalNAcβ1-4GlcNAc) structure 1111:1164 a sulphated LacDiNAc (LDN; GalNAcβ1-4GlcNAc) structure 1111:1164 Monoclonal antibodies to two immunodominant glycans of H. polygyrus, previously designated Glycans A and B, were found to react by glycan array analysis to a methyl-hexose-rich fraction and to a sulphated LacDiNAc (LDN; GalNAcβ1-4GlcNAc) structure, respectively. 26688390 4 60 theme glycan 1049:1054 arg1 analysis 1062:1069 glycan array analysis 1049:1069 glycan array analysis 1049:1069 Monoclonal antibodies to two immunodominant glycans of H. polygyrus, previously designated Glycans A and B, were found to react by glycan array analysis to a methyl-hexose-rich fraction and to a sulphated LacDiNAc (LDN; GalNAcβ1-4GlcNAc) structure, respectively. 26688390 6 61 theme mammalian 1897:1905 arg1 host 1907:1910 the mammalian host 1893:1910 the mammalian host 1893:1910 Taken together, these studies reveal that H. polygyrus secretes a diverse range of antigenic glycoconjugates, and provides a framework to explore the biological and immunomodulatory roles they may play within the mammalian host. 26688390 5 62 from present 1348:1354 arg1 products 1405:1412 Heligmosomoides polygyrus excretory-secretory products 1359:1412 Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation 1359:1681 We also analysed the glycan repertoire of a major glycoprotein in Heligmosomoides polygyrus excretory-secretory products, VAL-2, which contains many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation. 26688390 5 63 theme glycan 1202:1207 arg1 glycoprotein 1231:1242 a major glycoprotein 1223:1242 a major glycoprotein in Heligmosomoides polygyrus excretory-secretory products, VAL-2, which contains many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation 1223:1681 We also analysed the glycan repertoire of a major glycoprotein in Heligmosomoides polygyrus excretory-secretory products, VAL-2, which contains many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation. 26688390 5 63 theme glycan 1202:1207 arg1 repertoire 1209:1218 the glycan repertoire 1198:1218 the glycan repertoire of a major glycoprotein in Heligmosomoides polygyrus excretory-secretory products, VAL-2, which contains many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation 1198:1681 We also analysed the glycan repertoire of a major glycoprotein in Heligmosomoides polygyrus excretory-secretory products, VAL-2, which contains many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation. 26688390 4 64 dep H. 973:974 arg1 polygyrus 976:984 H. polygyrus 973:984 H. polygyrus 973:984 Monoclonal antibodies to two immunodominant glycans of H. polygyrus, previously designated Glycans A and B, were found to react by glycan array analysis to a methyl-hexose-rich fraction and to a sulphated LacDiNAc (LDN; GalNAcβ1-4GlcNAc) structure, respectively. 26688390 5 65 contain contains 1316:1323 arg2 structures 1337:1346 many glycan structures 1325:1346 many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation 1325:1681 We also analysed the glycan repertoire of a major glycoprotein in Heligmosomoides polygyrus excretory-secretory products, VAL-2, which contains many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation. 26688390 5 65 contain contains 1316:1323 arg1 which 1310:1314 which 1310:1314 which 1310:1314 We also analysed the glycan repertoire of a major glycoprotein in Heligmosomoides polygyrus excretory-secretory products, VAL-2, which contains many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation. 26688390 5 66 from repertoire 1209:1218 arg1 polygyrus 1263:1271 Heligmosomoides polygyrus excretory-secretory products, VAL-2, which contains many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation 1247:1681 polygyrus 1263:1271 We also analysed the glycan repertoire of a major glycoprotein in Heligmosomoides polygyrus excretory-secretory products, VAL-2, which contains many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation. 26688390 5 66 from repertoire 1209:1218 arg1 VAL-2 1303:1307 VAL-2 1303:1307 VAL-2 1303:1307 We also analysed the glycan repertoire of a major glycoprotein in Heligmosomoides polygyrus excretory-secretory products, VAL-2, which contains many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation. 26688390 3 67 theme O-linked 675:682 arg1 glycans 684:690 O-linked glycans 675:690 O-linked glycans released from Heligmosomoides polygyrus 675:730 We used MALDI-TOF-MS and LC-MS/MS to analyse the repertoire of N- and O-linked glycans released from Heligmosomoides polygyrus excretory-secretory products by PNGase A and F, β-elimination and hydrazinolysis revealing a broad range of structures including novel methylhexose- and methylfucose-containing glycans. 26688390 1 68 theme Glycan 145:150 arg1 molecules 152:160 Glycan molecules 145:160 Glycan molecules from helminth parasites 145:184 Glycan molecules from helminth parasites have been associated with diverse biological functions ranging from interactions with neighbouring host cell populations to down-modulation of specific host immunity. 26688390 3 69 theme excretory-secretory 732:750 arg1 products 752:759 excretory-secretory products 732:759 excretory-secretory products 732:759 We used MALDI-TOF-MS and LC-MS/MS to analyse the repertoire of N- and O-linked glycans released from Heligmosomoides polygyrus excretory-secretory products by PNGase A and F, β-elimination and hydrazinolysis revealing a broad range of structures including novel methylhexose- and methylfucose-containing glycans. 26688390 6 70 theme antigenic 1767:1775 arg1 glycoconjugates 1777:1791 antigenic glycoconjugates 1767:1791 antigenic glycoconjugates 1767:1791 Taken together, these studies reveal that H. polygyrus secretes a diverse range of antigenic glycoconjugates, and provides a framework to explore the biological and immunomodulatory roles they may play within the mammalian host. 26688390 5 71 attach present 1348:1354 arg2 structures 1337:1346 many glycan structures 1325:1346 many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation 1325:1681 We also analysed the glycan repertoire of a major glycoprotein in Heligmosomoides polygyrus excretory-secretory products, VAL-2, which contains many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation. 26688390 5 71 attach present 1348:1354 arg1 products 1405:1412 Heligmosomoides polygyrus excretory-secretory products 1359:1412 Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation 1359:1681 We also analysed the glycan repertoire of a major glycoprotein in Heligmosomoides polygyrus excretory-secretory products, VAL-2, which contains many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation. 26688390 3 72 theme Heligmosomoides 706:720 arg1 polygyrus 722:730 Heligmosomoides polygyrus 706:730 Heligmosomoides polygyrus 706:730 We used MALDI-TOF-MS and LC-MS/MS to analyse the repertoire of N- and O-linked glycans released from Heligmosomoides polygyrus excretory-secretory products by PNGase A and F, β-elimination and hydrazinolysis revealing a broad range of structures including novel methylhexose- and methylfucose-containing glycans. 26688390 1 73 theme neighbouring 272:283 arg1 populations 295:305 neighbouring host cell populations 272:305 neighbouring host cell populations 272:305 Glycan molecules from helminth parasites have been associated with diverse biological functions ranging from interactions with neighbouring host cell populations to down-modulation of specific host immunity. 26688390 0 74 theme intestinal 98:107 arg1 polygyrus 134:142 the intestinal nematode Heligmosomoides polygyrus 94:142 the intestinal nematode Heligmosomoides polygyrus 94:142 Novel O-linked methylated glycan antigens decorate secreted immunodominant glycoproteins from the intestinal nematode Heligmosomoides polygyrus. 26688390 3 75 dep N- 668:669 arg1 products 752:759 excretory-secretory products 732:759 excretory-secretory products 732:759 We used MALDI-TOF-MS and LC-MS/MS to analyse the repertoire of N- and O-linked glycans released from Heligmosomoides polygyrus excretory-secretory products by PNGase A and F, β-elimination and hydrazinolysis revealing a broad range of structures including novel methylhexose- and methylfucose-containing glycans. 26688390 3 76 attach released 692:699 arg1 polygyrus 722:730 Heligmosomoides polygyrus 706:730 Heligmosomoides polygyrus 706:730 We used MALDI-TOF-MS and LC-MS/MS to analyse the repertoire of N- and O-linked glycans released from Heligmosomoides polygyrus excretory-secretory products by PNGase A and F, β-elimination and hydrazinolysis revealing a broad range of structures including novel methylhexose- and methylfucose-containing glycans. 26688390 3 76 attach released 692:699 arg2 glycans 684:690 O-linked glycans 675:690 O-linked glycans released from Heligmosomoides polygyrus 675:730 We used MALDI-TOF-MS and LC-MS/MS to analyse the repertoire of N- and O-linked glycans released from Heligmosomoides polygyrus excretory-secretory products by PNGase A and F, β-elimination and hydrazinolysis revealing a broad range of structures including novel methylhexose- and methylfucose-containing glycans. 26688390 4 77 theme sulphated 1113:1121 arg1 LDN 1133:1135 LDN 1133:1135 LDN; GalNAcβ1-4GlcNAc 1133:1153 Monoclonal antibodies to two immunodominant glycans of H. polygyrus, previously designated Glycans A and B, were found to react by glycan array analysis to a methyl-hexose-rich fraction and to a sulphated LacDiNAc (LDN; GalNAcβ1-4GlcNAc) structure, respectively. 26688390 4 77 theme sulphated 1113:1121 arg1 LacDiNAc 1123:1130 sulphated LacDiNAc 1113:1130 a sulphated LacDiNAc (LDN; GalNAcβ1-4GlcNAc) structure 1111:1164 Monoclonal antibodies to two immunodominant glycans of H. polygyrus, previously designated Glycans A and B, were found to react by glycan array analysis to a methyl-hexose-rich fraction and to a sulphated LacDiNAc (LDN; GalNAcβ1-4GlcNAc) structure, respectively. 26688390 0 78 theme Heligmosomoides 118:132 arg1 polygyrus 134:142 the intestinal nematode Heligmosomoides polygyrus 94:142 the intestinal nematode Heligmosomoides polygyrus 94:142 Novel O-linked methylated glycan antigens decorate secreted immunodominant glycoproteins from the intestinal nematode Heligmosomoides polygyrus. 26688390 6 79 theme biological 1834:1843 arg1 roles 1866:1870 the biological and immunomodulatory roles 1830:1870 the biological and immunomodulatory roles they may play within the mammalian host 1830:1910 Taken together, these studies reveal that H. polygyrus secretes a diverse range of antigenic glycoconjugates, and provides a framework to explore the biological and immunomodulatory roles they may play within the mammalian host. 26688390 0 80 gly glycoproteins 75:87 arg1 glycoproteins 75:87 secreted immunodominant glycoproteins 51:87 secreted immunodominant glycoproteins from the intestinal nematode Heligmosomoides polygyrus 51:142 Novel O-linked methylated glycan antigens decorate secreted immunodominant glycoproteins from the intestinal nematode Heligmosomoides polygyrus. 26688390 5 81 theme major 1225:1229 arg1 glycoprotein 1231:1242 a major glycoprotein 1223:1242 a major glycoprotein in Heligmosomoides polygyrus excretory-secretory products, VAL-2, which contains many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation 1223:1681 We also analysed the glycan repertoire of a major glycoprotein in Heligmosomoides polygyrus excretory-secretory products, VAL-2, which contains many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation. 26688390 4 82 theme Monoclonal 918:927 arg1 antibodies 929:938 Monoclonal antibodies 918:938 Monoclonal antibodies to two immunodominant glycans of H. polygyrus, previously designated Glycans A and B, 918:1024 Monoclonal antibodies to two immunodominant glycans of H. polygyrus, previously designated Glycans A and B, were found to react by glycan array analysis to a methyl-hexose-rich fraction and to a sulphated LacDiNAc (LDN; GalNAcβ1-4GlcNAc) structure, respectively. 26688390 0 83 theme O-linked 6:13 arg1 antigens 33:40 Novel O-linked methylated glycan antigens 0:40 Novel O-linked methylated glycan antigens 0:40 Novel O-linked methylated glycan antigens decorate secreted immunodominant glycoproteins from the intestinal nematode Heligmosomoides polygyrus. 26688390 5 84 theme lung 1665:1668 arg1 inflammation 1670:1681 allergic lung inflammation 1656:1681 allergic lung inflammation 1656:1681 We also analysed the glycan repertoire of a major glycoprotein in Heligmosomoides polygyrus excretory-secretory products, VAL-2, which contains many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation. 26688390 0 85 theme glycan 26:31 arg1 antigens 33:40 Novel O-linked methylated glycan antigens 0:40 Novel O-linked methylated glycan antigens 0:40 Novel O-linked methylated glycan antigens decorate secreted immunodominant glycoproteins from the intestinal nematode Heligmosomoides polygyrus. 26688390 5 86 theme many 1325:1328 arg1 structures 1337:1346 many glycan structures 1325:1346 many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation 1325:1681 We also analysed the glycan repertoire of a major glycoprotein in Heligmosomoides polygyrus excretory-secretory products, VAL-2, which contains many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation. 26688390 1 87 with interactions 254:265 arg1 populations 295:305 neighbouring host cell populations 272:305 neighbouring host cell populations 272:305 Glycan molecules from helminth parasites have been associated with diverse biological functions ranging from interactions with neighbouring host cell populations to down-modulation of specific host immunity. 26688390 5 88 theme glycans 1473:1479 arg1 glycans 1473:1479 glycans 1473:1479 glycans 1473:1479 We also analysed the glycan repertoire of a major glycoprotein in Heligmosomoides polygyrus excretory-secretory products, VAL-2, which contains many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation. 26688390 5 88 theme glycans 1473:1479 arg1 set 1466:1468 this set 1461:1468 this set of glycans 1461:1479 We also analysed the glycan repertoire of a major glycoprotein in Heligmosomoides polygyrus excretory-secretory products, VAL-2, which contains many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation. 26688390 2 89 theme heat-stable 551:561 arg1 components 563:572 both heat-labile and heat-stable components 530:572 both heat-labile and heat-stable components 530:572 Glycoproteins secreted by the intestinal nematode Heligmosomoides polygyrus are of particular interest as the excretory-secretory products (termed HES) of this parasite contain both heat-labile and heat-stable components with immunomodulatory effects. 26688390 5 90 theme Heligmosomoides 1551:1565 arg1 polygyrus 1567:1575 Heligmosomoides polygyrus 1551:1575 Heligmosomoides polygyrus excretory-secretory products 1551:1604 We also analysed the glycan repertoire of a major glycoprotein in Heligmosomoides polygyrus excretory-secretory products, VAL-2, which contains many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation. 26688390 2 91 theme termed 493:498 arg1 products 483:490 the excretory-secretory products 459:490 the excretory-secretory products (termed HES) of this parasite 459:520 Glycoproteins secreted by the intestinal nematode Heligmosomoides polygyrus are of particular interest as the excretory-secretory products (termed HES) of this parasite contain both heat-labile and heat-stable components with immunomodulatory effects. 26688390 2 91 theme termed 493:498 arg1 HES 500:502 termed HES 493:502 termed HES 493:502 Glycoproteins secreted by the intestinal nematode Heligmosomoides polygyrus are of particular interest as the excretory-secretory products (termed HES) of this parasite contain both heat-labile and heat-stable components with immunomodulatory effects. 26688390 0 92 theme immunodominant 60:73 arg1 glycoproteins 75:87 secreted immunodominant glycoproteins 51:87 secreted immunodominant glycoproteins from the intestinal nematode Heligmosomoides polygyrus 51:142 Novel O-linked methylated glycan antigens decorate secreted immunodominant glycoproteins from the intestinal nematode Heligmosomoides polygyrus. 26688390 2 93 theme heat-labile 535:545 arg1 components 563:572 both heat-labile and heat-stable components 530:572 both heat-labile and heat-stable components 530:572 Glycoproteins secreted by the intestinal nematode Heligmosomoides polygyrus are of particular interest as the excretory-secretory products (termed HES) of this parasite contain both heat-labile and heat-stable components with immunomodulatory effects. 26688390 5 94 theme excretory-secretory 1577:1595 arg1 products 1597:1604 Heligmosomoides polygyrus excretory-secretory products 1551:1604 Heligmosomoides polygyrus excretory-secretory products 1551:1604 We also analysed the glycan repertoire of a major glycoprotein in Heligmosomoides polygyrus excretory-secretory products, VAL-2, which contains many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation. 26688390 5 95 theme heat-stable 1508:1518 arg1 properties 1537:1546 the heat-stable immunomodulatory properties 1504:1546 the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products 1504:1604 We also analysed the glycan repertoire of a major glycoprotein in Heligmosomoides polygyrus excretory-secretory products, VAL-2, which contains many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation. 26688390 2 96 theme nematode 394:401 arg1 polygyrus 419:427 the intestinal nematode Heligmosomoides polygyrus 379:427 the intestinal nematode Heligmosomoides polygyrus 379:427 Glycoproteins secreted by the intestinal nematode Heligmosomoides polygyrus are of particular interest as the excretory-secretory products (termed HES) of this parasite contain both heat-labile and heat-stable components with immunomodulatory effects. 26688390 1 97 theme host 285:288 arg1 populations 295:305 neighbouring host cell populations 272:305 neighbouring host cell populations 272:305 Glycan molecules from helminth parasites have been associated with diverse biological functions ranging from interactions with neighbouring host cell populations to down-modulation of specific host immunity. 26688390 4 98 theme immunodominant 947:960 arg1 B 1023:1023 B 1023:1023 B 1023:1023 Monoclonal antibodies to two immunodominant glycans of H. polygyrus, previously designated Glycans A and B, were found to react by glycan array analysis to a methyl-hexose-rich fraction and to a sulphated LacDiNAc (LDN; GalNAcβ1-4GlcNAc) structure, respectively. 26688390 4 98 theme immunodominant 947:960 arg1 A 1017:1017 previously designated Glycans A 987:1017 previously designated Glycans A 987:1017 Monoclonal antibodies to two immunodominant glycans of H. polygyrus, previously designated Glycans A and B, were found to react by glycan array analysis to a methyl-hexose-rich fraction and to a sulphated LacDiNAc (LDN; GalNAcβ1-4GlcNAc) structure, respectively. 26688390 4 98 theme immunodominant 947:960 arg1 glycans 962:968 two immunodominant glycans 943:968 two immunodominant glycans of H. polygyrus 943:984 Monoclonal antibodies to two immunodominant glycans of H. polygyrus, previously designated Glycans A and B, were found to react by glycan array analysis to a methyl-hexose-rich fraction and to a sulphated LacDiNAc (LDN; GalNAcβ1-4GlcNAc) structure, respectively. 26688390 5 99 from glycoprotein 1231:1242 arg1 polygyrus 1263:1271 Heligmosomoides polygyrus excretory-secretory products, VAL-2, which contains many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation 1247:1681 polygyrus 1263:1271 We also analysed the glycan repertoire of a major glycoprotein in Heligmosomoides polygyrus excretory-secretory products, VAL-2, which contains many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation. 26688390 5 99 from glycoprotein 1231:1242 arg1 VAL-2 1303:1307 VAL-2 1303:1307 VAL-2 1303:1307 We also analysed the glycan repertoire of a major glycoprotein in Heligmosomoides polygyrus excretory-secretory products, VAL-2, which contains many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation. 24854264 4 0 from survival 862:869 arg1 status 812:817 The dynamic status 800:817 The dynamic status of O-GlcNAcylation and effects on cellular survival 800:869 The dynamic status of O-GlcNAcylation and effects on cellular survival were investigated by chemical modulation with 6-diazo-5-oxo-L-norleucine (DON) to decrease or O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino N-phenyl carbamate (PUGNAc) to increase O-GlcNAc levels. 24854264 3 1 theme patients 706:713 arg1 effluent 691:698 human omentum or clinical effluent 665:698 human omentum or clinical effluent of PD patients 665:713 Immortalized human mesothelial cells and primary mesothelial cells, cultured from human omentum or clinical effluent of PD patients, were assessed for O-GlcNAcylation under normal conditions or after exposure to PDF. 24854264 9 2 theme important 1761:1769 arg1 O-GlcNAcylation 1707:1721 O-GlcNAcylation 1707:1721 O-GlcNAcylation 1707:1721 In conclusion, this study identified O-GlcNAcylation in mesothelial cells as a potentially important molecular mechanism after exposure to PDF. 24854264 9 2 theme important 1761:1769 arg1 mechanism 1781:1789 a potentially important molecular mechanism 1747:1789 a potentially important molecular mechanism after exposure to PDF 1747:1811 In conclusion, this study identified O-GlcNAcylation in mesothelial cells as a potentially important molecular mechanism after exposure to PDF. 24854264 6 3 theme improved 1309:1316 arg1 survival 1323:1330 significantly improved cell survival 1295:1330 significantly improved cell survival paralleled by higher heat shock protein 72 levels during PDF treatment 1295:1401 In contrast, increasing O-GlcNAc levels by PUGNAc or alanyl-glutamine led to significantly improved cell survival paralleled by higher heat shock protein 72 levels during PDF treatment. 24854264 7 4 theme improved 1522:1529 arg1 survival 1536:1543 improved cell survival 1522:1543 improved cell survival 1522:1543 Addition of alanyl-glutamine increased O-GlcNAcylation and partly counteracted its inhibition by DON, also leading to improved cell survival. 24854264 10 5 theme therapeutic 1902:1912 arg1 target 1914:1919 a novel therapeutic target 1894:1919 a novel therapeutic target for the preservation of peritoneal membrane integrity in PD 1894:1979 Modulating O-GlcNAc levels by clinically feasible interventions might evolve as a novel therapeutic target for the preservation of peritoneal membrane integrity in PD. 24854264 6 6 theme PDF 1389:1391 arg1 treatment 1393:1401 PDF treatment 1389:1401 PDF treatment 1389:1401 In contrast, increasing O-GlcNAc levels by PUGNAc or alanyl-glutamine led to significantly improved cell survival paralleled by higher heat shock protein 72 levels during PDF treatment. 24854264 3 7 theme primary 624:630 arg1 cells 644:648 primary mesothelial cells 624:648 primary mesothelial cells 624:648 Immortalized human mesothelial cells and primary mesothelial cells, cultured from human omentum or clinical effluent of PD patients, were assessed for O-GlcNAcylation under normal conditions or after exposure to PDF. 24854264 6 8 theme protein 1364:1370 arg1 levels 1375:1380 heat shock protein 72 levels 1353:1380 heat shock protein 72 levels 1353:1380 In contrast, increasing O-GlcNAc levels by PUGNAc or alanyl-glutamine led to significantly improved cell survival paralleled by higher heat shock protein 72 levels during PDF treatment. 24854264 4 9 from effects 842:848 arg1 survival 862:869 cellular survival 853:869 cellular survival 853:869 The dynamic status of O-GlcNAcylation and effects on cellular survival were investigated by chemical modulation with 6-diazo-5-oxo-L-norleucine (DON) to decrease or O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino N-phenyl carbamate (PUGNAc) to increase O-GlcNAc levels. 24854264 6 10 theme heat 1353:1356 arg1 protein 1364:1370 heat shock protein 72 1353:1373 heat shock protein 72 levels 1353:1380 In contrast, increasing O-GlcNAc levels by PUGNAc or alanyl-glutamine led to significantly improved cell survival paralleled by higher heat shock protein 72 levels during PDF treatment. 24854264 5 11 theme O-GlcNAc 1109:1116 arg1 levels 1118:1123 O-GlcNAc levels 1109:1123 O-GlcNAc levels 1109:1123 Viability was decreased by reducing O-GlcNAc levels by DON, which also led to suppressed expression of the cytoprotective heat shock protein 72. 24854264 10 12 theme integrity 1965:1973 arg1 preservation 1929:1940 the preservation 1925:1940 the preservation of peritoneal membrane integrity in PD 1925:1979 Modulating O-GlcNAc levels by clinically feasible interventions might evolve as a novel therapeutic target for the preservation of peritoneal membrane integrity in PD. 24854264 4 13 from O-GlcNAcylation 822:836 arg1 survival 862:869 cellular survival 853:869 cellular survival 853:869 The dynamic status of O-GlcNAcylation and effects on cellular survival were investigated by chemical modulation with 6-diazo-5-oxo-L-norleucine (DON) to decrease or O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino N-phenyl carbamate (PUGNAc) to increase O-GlcNAc levels. 24854264 4 14 with modulation 901:910 arg1 DON 945:947 DON 945:947 DON 945:947 The dynamic status of O-GlcNAcylation and effects on cellular survival were investigated by chemical modulation with 6-diazo-5-oxo-L-norleucine (DON) to decrease or O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino N-phenyl carbamate (PUGNAc) to increase O-GlcNAc levels. 24854264 4 14 with modulation 901:910 arg1 6-diazo-5-oxo-L-norleucine 917:942 6-diazo-5-oxo-L-norleucine 917:942 6-diazo-5-oxo-L-norleucine (DON) to decrease or O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino N-phenyl carbamate (PUGNAc) 917:1042 The dynamic status of O-GlcNAcylation and effects on cellular survival were investigated by chemical modulation with 6-diazo-5-oxo-L-norleucine (DON) to decrease or O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino N-phenyl carbamate (PUGNAc) to increase O-GlcNAc levels. 24854264 6 15 theme O-GlcNAc 1242:1249 arg1 levels 1251:1256 O-GlcNAc levels 1242:1256 O-GlcNAc levels 1242:1256 In contrast, increasing O-GlcNAc levels by PUGNAc or alanyl-glutamine led to significantly improved cell survival paralleled by higher heat shock protein 72 levels during PDF treatment. 24854264 10 16 theme peritoneal 1945:1954 arg1 integrity 1965:1973 peritoneal membrane integrity 1945:1973 peritoneal membrane integrity 1945:1973 Modulating O-GlcNAc levels by clinically feasible interventions might evolve as a novel therapeutic target for the preservation of peritoneal membrane integrity in PD. 24854264 4 17 from status 812:817 arg1 survival 862:869 cellular survival 853:869 cellular survival 853:869 The dynamic status of O-GlcNAcylation and effects on cellular survival were investigated by chemical modulation with 6-diazo-5-oxo-L-norleucine (DON) to decrease or O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino N-phenyl carbamate (PUGNAc) to increase O-GlcNAc levels. 24854264 2 18 theme cell 503:506 arg1 survival 508:515 cell survival 503:515 cell survival 503:515 This study investigates the role of dynamic O-GlcNAcylation of mesothelial cell proteins in cell survival during exposure to glucose-based peritoneal dialysis fluid (PDF). 24854264 2 19 from role 439:442 arg1 survival 508:515 cell survival 503:515 cell survival 503:515 This study investigates the role of dynamic O-GlcNAcylation of mesothelial cell proteins in cell survival during exposure to glucose-based peritoneal dialysis fluid (PDF). 24854264 1 20 theme cells 175:179 arg1 ability 164:170 The ability 160:170 The ability of cells to respond and survive stressful conditions 160:223 The ability of cells to respond and survive stressful conditions is determined, in part, by the attachment of O-linked N-acetylglucosamine (O-GlcNAc) to proteins (O-GlcNAcylation), a post-translational modification dependent on glucose and glutamine. 24854264 2 21 theme peritoneal 550:559 arg1 PDF 577:579 PDF 577:579 PDF 577:579 This study investigates the role of dynamic O-GlcNAcylation of mesothelial cell proteins in cell survival during exposure to glucose-based peritoneal dialysis fluid (PDF). 24854264 2 21 theme peritoneal 550:559 arg1 fluid 570:574 glucose-based peritoneal dialysis fluid 536:574 glucose-based peritoneal dialysis fluid (PDF) 536:580 This study investigates the role of dynamic O-GlcNAcylation of mesothelial cell proteins in cell survival during exposure to glucose-based peritoneal dialysis fluid (PDF). 24854264 0 22 theme mesothelial 103:113 arg1 cells 115:119 mesothelial cells 103:119 mesothelial cells exposed to peritoneal dialysis fluids 103:157 Dynamic O-linked N-acetylglucosamine modification of proteins affects stress responses and survival of mesothelial cells exposed to peritoneal dialysis fluids. 24854264 1 23 theme post-translational 343:360 arg1 modification 362:373 a post-translational modification 341:373 a post-translational modification dependent on glucose and glutamine 341:408 The ability of cells to respond and survive stressful conditions is determined, in part, by the attachment of O-linked N-acetylglucosamine (O-GlcNAc) to proteins (O-GlcNAcylation), a post-translational modification dependent on glucose and glutamine. 24854264 1 23 theme post-translational 343:360 arg1 proteins 313:320 proteins 313:320 proteins (O-GlcNAcylation) 313:338 The ability of cells to respond and survive stressful conditions is determined, in part, by the attachment of O-linked N-acetylglucosamine (O-GlcNAc) to proteins (O-GlcNAcylation), a post-translational modification dependent on glucose and glutamine. 24854264 4 24 theme N-phenyl 1016:1023 arg1 PUGNAc 1036:1041 PUGNAc 1036:1041 PUGNAc 1036:1041 The dynamic status of O-GlcNAcylation and effects on cellular survival were investigated by chemical modulation with 6-diazo-5-oxo-L-norleucine (DON) to decrease or O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino N-phenyl carbamate (PUGNAc) to increase O-GlcNAc levels. 24854264 4 24 theme N-phenyl 1016:1023 arg1 carbamate 1025:1033 O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino N-phenyl carbamate 965:1033 O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino N-phenyl carbamate (PUGNAc) 965:1042 The dynamic status of O-GlcNAcylation and effects on cellular survival were investigated by chemical modulation with 6-diazo-5-oxo-L-norleucine (DON) to decrease or O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino N-phenyl carbamate (PUGNAc) to increase O-GlcNAc levels. 24854264 1 25 theme dependent 375:383 arg1 modification 362:373 a post-translational modification 341:373 a post-translational modification dependent on glucose and glutamine 341:408 The ability of cells to respond and survive stressful conditions is determined, in part, by the attachment of O-linked N-acetylglucosamine (O-GlcNAc) to proteins (O-GlcNAcylation), a post-translational modification dependent on glucose and glutamine. 24854264 1 25 theme dependent 375:383 arg1 proteins 313:320 proteins 313:320 proteins (O-GlcNAcylation) 313:338 The ability of cells to respond and survive stressful conditions is determined, in part, by the attachment of O-linked N-acetylglucosamine (O-GlcNAc) to proteins (O-GlcNAcylation), a post-translational modification dependent on glucose and glutamine. 24854264 2 26 theme O-GlcNAcylation 455:469 arg1 role 439:442 the role 435:442 the role of dynamic O-GlcNAcylation of mesothelial cell proteins in cell survival 435:515 This study investigates the role of dynamic O-GlcNAcylation of mesothelial cell proteins in cell survival during exposure to glucose-based peritoneal dialysis fluid (PDF). 24854264 0 27 theme Dynamic 0:6 arg1 modification 37:48 Dynamic O-linked N-acetylglucosamine modification 0:48 Dynamic O-linked N-acetylglucosamine modification of proteins 0:60 Dynamic O-linked N-acetylglucosamine modification of proteins affects stress responses and survival of mesothelial cells exposed to peritoneal dialysis fluids. 24854264 1 28 theme O-linked 270:277 arg1 O-GlcNAc 300:307 O-GlcNAc 300:307 O-GlcNAc 300:307 The ability of cells to respond and survive stressful conditions is determined, in part, by the attachment of O-linked N-acetylglucosamine (O-GlcNAc) to proteins (O-GlcNAcylation), a post-translational modification dependent on glucose and glutamine. 24854264 1 28 theme O-linked 270:277 arg1 N-acetylglucosamine 279:297 O-linked N-acetylglucosamine 270:297 O-linked N-acetylglucosamine (O-GlcNAc) 270:308 The ability of cells to respond and survive stressful conditions is determined, in part, by the attachment of O-linked N-acetylglucosamine (O-GlcNAc) to proteins (O-GlcNAcylation), a post-translational modification dependent on glucose and glutamine. 24854264 3 29 theme mesothelial 632:642 arg1 cells 644:648 primary mesothelial cells 624:648 primary mesothelial cells 624:648 Immortalized human mesothelial cells and primary mesothelial cells, cultured from human omentum or clinical effluent of PD patients, were assessed for O-GlcNAcylation under normal conditions or after exposure to PDF. 24854264 0 30 theme N-acetylglucosamine 17:35 arg1 modification 37:48 Dynamic O-linked N-acetylglucosamine modification 0:48 Dynamic O-linked N-acetylglucosamine modification of proteins 0:60 Dynamic O-linked N-acetylglucosamine modification of proteins affects stress responses and survival of mesothelial cells exposed to peritoneal dialysis fluids. 24854264 2 31 theme proteins 491:498 arg1 O-GlcNAcylation 455:469 dynamic O-GlcNAcylation 447:469 dynamic O-GlcNAcylation of mesothelial cell proteins 447:498 This study investigates the role of dynamic O-GlcNAcylation of mesothelial cell proteins in cell survival during exposure to glucose-based peritoneal dialysis fluid (PDF). 24854264 8 32 theme mesothelial 1651:1661 arg1 cells 1663:1667 mesothelial cells 1651:1667 mesothelial cells 1651:1667 Immunofluorescent analysis of clinical samples showed that the O-GlcNAc signal primarily originates from mesothelial cells. 24854264 4 33 theme effects 842:848 arg1 status 812:817 The dynamic status 800:817 The dynamic status of O-GlcNAcylation and effects on cellular survival 800:869 The dynamic status of O-GlcNAcylation and effects on cellular survival were investigated by chemical modulation with 6-diazo-5-oxo-L-norleucine (DON) to decrease or O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino N-phenyl carbamate (PUGNAc) to increase O-GlcNAc levels. 24854264 5 34 theme heat 1195:1198 arg1 protein 1206:1212 the cytoprotective heat shock protein 72 1176:1215 the cytoprotective heat shock protein 72 1176:1215 Viability was decreased by reducing O-GlcNAc levels by DON, which also led to suppressed expression of the cytoprotective heat shock protein 72. 24854264 2 35 theme mesothelial 474:484 arg1 proteins 491:498 mesothelial cell proteins 474:498 mesothelial cell proteins 474:498 This study investigates the role of dynamic O-GlcNAcylation of mesothelial cell proteins in cell survival during exposure to glucose-based peritoneal dialysis fluid (PDF). 24854264 0 36 mod modification 37:48 arg1 proteins 53:60 proteins 53:60 proteins 53:60 Dynamic O-linked N-acetylglucosamine modification of proteins affects stress responses and survival of mesothelial cells exposed to peritoneal dialysis fluids. 24854264 0 36 mod modification 37:48 arg3 N-acetylglucosamine 17:35 Dynamic O-linked N-acetylglucosamine modification 0:48 Dynamic O-linked N-acetylglucosamine modification of proteins 0:60 Dynamic O-linked N-acetylglucosamine modification of proteins affects stress responses and survival of mesothelial cells exposed to peritoneal dialysis fluids. 24854264 3 37 theme human 665:669 arg1 effluent 691:698 human omentum or clinical effluent 665:698 human omentum or clinical effluent of PD patients 665:713 Immortalized human mesothelial cells and primary mesothelial cells, cultured from human omentum or clinical effluent of PD patients, were assessed for O-GlcNAcylation under normal conditions or after exposure to PDF. 24854264 4 38 theme cellular 853:860 arg1 survival 862:869 cellular survival 853:869 cellular survival 853:869 The dynamic status of O-GlcNAcylation and effects on cellular survival were investigated by chemical modulation with 6-diazo-5-oxo-L-norleucine (DON) to decrease or O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino N-phenyl carbamate (PUGNAc) to increase O-GlcNAc levels. 24854264 10 39 theme O-GlcNAc 1825:1832 arg1 levels 1834:1839 O-GlcNAc levels 1825:1839 O-GlcNAc levels 1825:1839 Modulating O-GlcNAc levels by clinically feasible interventions might evolve as a novel therapeutic target for the preservation of peritoneal membrane integrity in PD. 24854264 5 40 theme protein 1206:1212 arg1 expression 1162:1171 suppressed expression 1151:1171 suppressed expression of the cytoprotective heat shock protein 72 1151:1215 Viability was decreased by reducing O-GlcNAc levels by DON, which also led to suppressed expression of the cytoprotective heat shock protein 72. 24854264 1 41 attach attachment 256:265 arg2 O-GlcNAc 300:307 O-GlcNAc 300:307 O-GlcNAc 300:307 The ability of cells to respond and survive stressful conditions is determined, in part, by the attachment of O-linked N-acetylglucosamine (O-GlcNAc) to proteins (O-GlcNAcylation), a post-translational modification dependent on glucose and glutamine. 24854264 1 41 attach attachment 256:265 arg1 O-GlcNAcylation 323:337 O-GlcNAcylation 323:337 O-GlcNAcylation 323:337 The ability of cells to respond and survive stressful conditions is determined, in part, by the attachment of O-linked N-acetylglucosamine (O-GlcNAc) to proteins (O-GlcNAcylation), a post-translational modification dependent on glucose and glutamine. 24854264 1 41 attach attachment 256:265 arg1 proteins 313:320 proteins 313:320 proteins (O-GlcNAcylation) 313:338 The ability of cells to respond and survive stressful conditions is determined, in part, by the attachment of O-linked N-acetylglucosamine (O-GlcNAc) to proteins (O-GlcNAcylation), a post-translational modification dependent on glucose and glutamine. 24854264 1 41 attach attachment 256:265 arg2 N-acetylglucosamine 279:297 O-linked N-acetylglucosamine 270:297 O-linked N-acetylglucosamine (O-GlcNAc) 270:308 The ability of cells to respond and survive stressful conditions is determined, in part, by the attachment of O-linked N-acetylglucosamine (O-GlcNAc) to proteins (O-GlcNAcylation), a post-translational modification dependent on glucose and glutamine. 24854264 1 41 attach attachment 256:265 arg1 modification 362:373 a post-translational modification 341:373 a post-translational modification dependent on glucose and glutamine 341:408 The ability of cells to respond and survive stressful conditions is determined, in part, by the attachment of O-linked N-acetylglucosamine (O-GlcNAc) to proteins (O-GlcNAcylation), a post-translational modification dependent on glucose and glutamine. 24854264 3 42 theme PD 703:704 arg1 patients 706:713 PD patients 703:713 PD patients 703:713 Immortalized human mesothelial cells and primary mesothelial cells, cultured from human omentum or clinical effluent of PD patients, were assessed for O-GlcNAcylation under normal conditions or after exposure to PDF. 24854264 9 43 theme mesothelial 1726:1736 arg1 cells 1738:1742 mesothelial cells 1726:1742 mesothelial cells 1726:1742 In conclusion, this study identified O-GlcNAcylation in mesothelial cells as a potentially important molecular mechanism after exposure to PDF. 24854264 4 44 theme O-GlcNAcylation 822:836 arg1 status 812:817 The dynamic status 800:817 The dynamic status of O-GlcNAcylation and effects on cellular survival 800:869 The dynamic status of O-GlcNAcylation and effects on cellular survival were investigated by chemical modulation with 6-diazo-5-oxo-L-norleucine (DON) to decrease or O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino N-phenyl carbamate (PUGNAc) to increase O-GlcNAc levels. 24854264 10 45 theme feasible 1855:1862 arg1 interventions 1864:1876 clinically feasible interventions 1844:1876 clinically feasible interventions 1844:1876 Modulating O-GlcNAc levels by clinically feasible interventions might evolve as a novel therapeutic target for the preservation of peritoneal membrane integrity in PD. 24854264 8 46 theme clinical 1576:1583 arg1 samples 1585:1591 clinical samples 1576:1591 clinical samples 1576:1591 Immunofluorescent analysis of clinical samples showed that the O-GlcNAc signal primarily originates from mesothelial cells. 24854264 4 47 theme chemical 892:899 arg1 modulation 901:910 chemical modulation 892:910 chemical modulation with 6-diazo-5-oxo-L-norleucine (DON) to decrease or O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino N-phenyl carbamate (PUGNAc) to increase O-GlcNAc levels 892:1070 The dynamic status of O-GlcNAcylation and effects on cellular survival were investigated by chemical modulation with 6-diazo-5-oxo-L-norleucine (DON) to decrease or O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino N-phenyl carbamate (PUGNAc) to increase O-GlcNAc levels. 24854264 7 48 theme cell 1531:1534 arg1 survival 1536:1543 improved cell survival 1522:1543 improved cell survival 1522:1543 Addition of alanyl-glutamine increased O-GlcNAcylation and partly counteracted its inhibition by DON, also leading to improved cell survival. 24854264 9 49 theme molecular 1771:1779 arg1 O-GlcNAcylation 1707:1721 O-GlcNAcylation 1707:1721 O-GlcNAcylation 1707:1721 In conclusion, this study identified O-GlcNAcylation in mesothelial cells as a potentially important molecular mechanism after exposure to PDF. 24854264 9 49 theme molecular 1771:1779 arg1 mechanism 1781:1789 a potentially important molecular mechanism 1747:1789 a potentially important molecular mechanism after exposure to PDF 1747:1811 In conclusion, this study identified O-GlcNAcylation in mesothelial cells as a potentially important molecular mechanism after exposure to PDF. 24854264 0 50 link O-linked 8:15 arg1 modification 37:48 Dynamic O-linked N-acetylglucosamine modification 0:48 Dynamic O-linked N-acetylglucosamine modification of proteins 0:60 Dynamic O-linked N-acetylglucosamine modification of proteins affects stress responses and survival of mesothelial cells exposed to peritoneal dialysis fluids. 24854264 3 51 theme normal 756:761 arg1 conditions 763:772 normal conditions 756:772 normal conditions 756:772 Immortalized human mesothelial cells and primary mesothelial cells, cultured from human omentum or clinical effluent of PD patients, were assessed for O-GlcNAcylation under normal conditions or after exposure to PDF. 24854264 6 52 theme cell 1318:1321 arg1 survival 1323:1330 significantly improved cell survival 1295:1330 significantly improved cell survival paralleled by higher heat shock protein 72 levels during PDF treatment 1295:1401 In contrast, increasing O-GlcNAc levels by PUGNAc or alanyl-glutamine led to significantly improved cell survival paralleled by higher heat shock protein 72 levels during PDF treatment. 24854264 4 53 theme O-GlcNAc 1056:1063 arg1 levels 1065:1070 O-GlcNAc levels 1056:1070 O-GlcNAc levels 1056:1070 The dynamic status of O-GlcNAcylation and effects on cellular survival were investigated by chemical modulation with 6-diazo-5-oxo-L-norleucine (DON) to decrease or O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino N-phenyl carbamate (PUGNAc) to increase O-GlcNAc levels. 24854264 3 54 theme Immortalized 583:594 arg1 cells 614:618 human mesothelial cells 596:618 human mesothelial cells 596:618 Immortalized human mesothelial cells and primary mesothelial cells, cultured from human omentum or clinical effluent of PD patients, were assessed for O-GlcNAcylation under normal conditions or after exposure to PDF. 24854264 0 55 theme dialysis 143:150 arg1 fluids 152:157 peritoneal dialysis fluids 132:157 peritoneal dialysis fluids 132:157 Dynamic O-linked N-acetylglucosamine modification of proteins affects stress responses and survival of mesothelial cells exposed to peritoneal dialysis fluids. 24854264 10 56 theme novel 1896:1900 arg1 target 1914:1919 a novel therapeutic target 1894:1919 a novel therapeutic target for the preservation of peritoneal membrane integrity in PD 1894:1979 Modulating O-GlcNAc levels by clinically feasible interventions might evolve as a novel therapeutic target for the preservation of peritoneal membrane integrity in PD. 24854264 1 57 theme stressful 204:212 arg1 conditions 214:223 stressful conditions 204:223 stressful conditions 204:223 The ability of cells to respond and survive stressful conditions is determined, in part, by the attachment of O-linked N-acetylglucosamine (O-GlcNAc) to proteins (O-GlcNAcylation), a post-translational modification dependent on glucose and glutamine. 24854264 3 58 theme human 596:600 arg1 cells 614:618 human mesothelial cells 596:618 human mesothelial cells 596:618 Immortalized human mesothelial cells and primary mesothelial cells, cultured from human omentum or clinical effluent of PD patients, were assessed for O-GlcNAcylation under normal conditions or after exposure to PDF. 24854264 6 59 dep levels 1375:1380 arg1 higher 1346:1351 higher 1346:1351 higher 1346:1351 In contrast, increasing O-GlcNAc levels by PUGNAc or alanyl-glutamine led to significantly improved cell survival paralleled by higher heat shock protein 72 levels during PDF treatment. 24854264 4 60 theme O- 965:966 arg1 PUGNAc 1036:1041 PUGNAc 1036:1041 PUGNAc 1036:1041 The dynamic status of O-GlcNAcylation and effects on cellular survival were investigated by chemical modulation with 6-diazo-5-oxo-L-norleucine (DON) to decrease or O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino N-phenyl carbamate (PUGNAc) to increase O-GlcNAc levels. 24854264 4 60 theme O- 965:966 arg1 carbamate 1025:1033 O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino N-phenyl carbamate 965:1033 O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino N-phenyl carbamate (PUGNAc) 965:1042 The dynamic status of O-GlcNAcylation and effects on cellular survival were investigated by chemical modulation with 6-diazo-5-oxo-L-norleucine (DON) to decrease or O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino N-phenyl carbamate (PUGNAc) to increase O-GlcNAc levels. 24854264 3 61 theme mesothelial 602:612 arg1 cells 614:618 human mesothelial cells 596:618 human mesothelial cells 596:618 Immortalized human mesothelial cells and primary mesothelial cells, cultured from human omentum or clinical effluent of PD patients, were assessed for O-GlcNAcylation under normal conditions or after exposure to PDF. 24854264 8 62 theme Immunofluorescent 1546:1562 arg1 analysis 1564:1571 Immunofluorescent analysis 1546:1571 Immunofluorescent analysis of clinical samples 1546:1591 Immunofluorescent analysis of clinical samples showed that the O-GlcNAc signal primarily originates from mesothelial cells. 24854264 6 63 theme shock 1358:1362 arg1 protein 1364:1370 heat shock protein 72 1353:1373 heat shock protein 72 levels 1353:1380 In contrast, increasing O-GlcNAc levels by PUGNAc or alanyl-glutamine led to significantly improved cell survival paralleled by higher heat shock protein 72 levels during PDF treatment. 24854264 7 64 theme alanyl-glutamine 1416:1431 arg1 Addition 1404:1411 Addition 1404:1411 Addition of alanyl-glutamine 1404:1431 Addition of alanyl-glutamine increased O-GlcNAcylation and partly counteracted its inhibition by DON, also leading to improved cell survival. 24854264 10 65 theme membrane 1956:1963 arg1 integrity 1965:1973 peritoneal membrane integrity 1945:1973 peritoneal membrane integrity 1945:1973 Modulating O-GlcNAc levels by clinically feasible interventions might evolve as a novel therapeutic target for the preservation of peritoneal membrane integrity in PD. 24854264 8 66 theme samples 1585:1591 arg1 analysis 1564:1571 Immunofluorescent analysis 1546:1571 Immunofluorescent analysis of clinical samples 1546:1591 Immunofluorescent analysis of clinical samples showed that the O-GlcNAc signal primarily originates from mesothelial cells. 24854264 2 67 theme glucose-based 536:548 arg1 PDF 577:579 PDF 577:579 PDF 577:579 This study investigates the role of dynamic O-GlcNAcylation of mesothelial cell proteins in cell survival during exposure to glucose-based peritoneal dialysis fluid (PDF). 24854264 2 67 theme glucose-based 536:548 arg1 fluid 570:574 glucose-based peritoneal dialysis fluid 536:574 glucose-based peritoneal dialysis fluid (PDF) 536:580 This study investigates the role of dynamic O-GlcNAcylation of mesothelial cell proteins in cell survival during exposure to glucose-based peritoneal dialysis fluid (PDF). 24854264 0 68 theme peritoneal 132:141 arg1 fluids 152:157 peritoneal dialysis fluids 132:157 peritoneal dialysis fluids 132:157 Dynamic O-linked N-acetylglucosamine modification of proteins affects stress responses and survival of mesothelial cells exposed to peritoneal dialysis fluids. 24854264 0 69 theme cells 115:119 arg1 survival 91:98 survival 91:98 survival of mesothelial cells exposed to peritoneal dialysis fluids 91:157 Dynamic O-linked N-acetylglucosamine modification of proteins affects stress responses and survival of mesothelial cells exposed to peritoneal dialysis fluids. 24854264 0 69 theme cells 115:119 arg1 responses 77:85 stress responses 70:85 stress responses 70:85 Dynamic O-linked N-acetylglucosamine modification of proteins affects stress responses and survival of mesothelial cells exposed to peritoneal dialysis fluids. 24854264 5 70 theme cytoprotective 1180:1193 arg1 protein 1206:1212 the cytoprotective heat shock protein 72 1176:1215 the cytoprotective heat shock protein 72 1176:1215 Viability was decreased by reducing O-GlcNAc levels by DON, which also led to suppressed expression of the cytoprotective heat shock protein 72. 24854264 4 71 theme 2-acetamido-2-deoxy-D-glucopyranosylidene 968:1008 arg1 PUGNAc 1036:1041 PUGNAc 1036:1041 PUGNAc 1036:1041 The dynamic status of O-GlcNAcylation and effects on cellular survival were investigated by chemical modulation with 6-diazo-5-oxo-L-norleucine (DON) to decrease or O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino N-phenyl carbamate (PUGNAc) to increase O-GlcNAc levels. 24854264 4 71 theme 2-acetamido-2-deoxy-D-glucopyranosylidene 968:1008 arg1 carbamate 1025:1033 O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino N-phenyl carbamate 965:1033 O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino N-phenyl carbamate (PUGNAc) 965:1042 The dynamic status of O-GlcNAcylation and effects on cellular survival were investigated by chemical modulation with 6-diazo-5-oxo-L-norleucine (DON) to decrease or O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino N-phenyl carbamate (PUGNAc) to increase O-GlcNAc levels. 24854264 8 72 theme O-GlcNAc 1609:1616 arg1 signal 1618:1623 the O-GlcNAc signal 1605:1623 the O-GlcNAc signal 1605:1623 Immunofluorescent analysis of clinical samples showed that the O-GlcNAc signal primarily originates from mesothelial cells. 24854264 4 73 theme amino 1010:1014 arg1 PUGNAc 1036:1041 PUGNAc 1036:1041 PUGNAc 1036:1041 The dynamic status of O-GlcNAcylation and effects on cellular survival were investigated by chemical modulation with 6-diazo-5-oxo-L-norleucine (DON) to decrease or O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino N-phenyl carbamate (PUGNAc) to increase O-GlcNAc levels. 24854264 4 73 theme amino 1010:1014 arg1 carbamate 1025:1033 O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino N-phenyl carbamate 965:1033 O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino N-phenyl carbamate (PUGNAc) 965:1042 The dynamic status of O-GlcNAcylation and effects on cellular survival were investigated by chemical modulation with 6-diazo-5-oxo-L-norleucine (DON) to decrease or O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino N-phenyl carbamate (PUGNAc) to increase O-GlcNAc levels. 24854264 0 74 theme O-linked 8:15 arg1 modification 37:48 Dynamic O-linked N-acetylglucosamine modification 0:48 Dynamic O-linked N-acetylglucosamine modification of proteins 0:60 Dynamic O-linked N-acetylglucosamine modification of proteins affects stress responses and survival of mesothelial cells exposed to peritoneal dialysis fluids. 24854264 5 75 theme suppressed 1151:1160 arg1 expression 1162:1171 suppressed expression 1151:1171 suppressed expression of the cytoprotective heat shock protein 72 1151:1215 Viability was decreased by reducing O-GlcNAc levels by DON, which also led to suppressed expression of the cytoprotective heat shock protein 72. 24854264 10 76 from preservation 1929:1940 arg1 PD 1978:1979 PD 1978:1979 PD 1978:1979 Modulating O-GlcNAc levels by clinically feasible interventions might evolve as a novel therapeutic target for the preservation of peritoneal membrane integrity in PD. 24854264 2 77 theme dynamic 447:453 arg1 O-GlcNAcylation 455:469 dynamic O-GlcNAcylation 447:469 dynamic O-GlcNAcylation of mesothelial cell proteins 447:498 This study investigates the role of dynamic O-GlcNAcylation of mesothelial cell proteins in cell survival during exposure to glucose-based peritoneal dialysis fluid (PDF). 24854264 1 78 theme N-acetylglucosamine 279:297 arg1 attachment 256:265 the attachment 252:265 the attachment of O-linked N-acetylglucosamine (O-GlcNAc) to proteins (O-GlcNAcylation), a post-translational modification dependent on glucose and glutamine 252:408 The ability of cells to respond and survive stressful conditions is determined, in part, by the attachment of O-linked N-acetylglucosamine (O-GlcNAc) to proteins (O-GlcNAcylation), a post-translational modification dependent on glucose and glutamine. 24854264 3 79 theme omentum 671:677 arg1 effluent 691:698 human omentum or clinical effluent 665:698 human omentum or clinical effluent of PD patients 665:713 Immortalized human mesothelial cells and primary mesothelial cells, cultured from human omentum or clinical effluent of PD patients, were assessed for O-GlcNAcylation under normal conditions or after exposure to PDF. 24854264 0 80 theme proteins 53:60 arg1 modification 37:48 Dynamic O-linked N-acetylglucosamine modification 0:48 Dynamic O-linked N-acetylglucosamine modification of proteins 0:60 Dynamic O-linked N-acetylglucosamine modification of proteins affects stress responses and survival of mesothelial cells exposed to peritoneal dialysis fluids. 24854264 2 81 theme cell 486:489 arg1 proteins 491:498 mesothelial cell proteins 474:498 mesothelial cell proteins 474:498 This study investigates the role of dynamic O-GlcNAcylation of mesothelial cell proteins in cell survival during exposure to glucose-based peritoneal dialysis fluid (PDF). 24854264 0 82 theme stress 70:75 arg1 responses 77:85 stress responses 70:85 stress responses 70:85 Dynamic O-linked N-acetylglucosamine modification of proteins affects stress responses and survival of mesothelial cells exposed to peritoneal dialysis fluids. 24854264 5 83 theme shock 1200:1204 arg1 protein 1206:1212 the cytoprotective heat shock protein 72 1176:1215 the cytoprotective heat shock protein 72 1176:1215 Viability was decreased by reducing O-GlcNAc levels by DON, which also led to suppressed expression of the cytoprotective heat shock protein 72. 24854264 2 84 theme dialysis 561:568 arg1 PDF 577:579 PDF 577:579 PDF 577:579 This study investigates the role of dynamic O-GlcNAcylation of mesothelial cell proteins in cell survival during exposure to glucose-based peritoneal dialysis fluid (PDF). 24854264 2 84 theme dialysis 561:568 arg1 fluid 570:574 glucose-based peritoneal dialysis fluid 536:574 glucose-based peritoneal dialysis fluid (PDF) 536:580 This study investigates the role of dynamic O-GlcNAcylation of mesothelial cell proteins in cell survival during exposure to glucose-based peritoneal dialysis fluid (PDF). 24854264 3 85 theme clinical 682:689 arg1 effluent 691:698 human omentum or clinical effluent 665:698 human omentum or clinical effluent of PD patients 665:713 Immortalized human mesothelial cells and primary mesothelial cells, cultured from human omentum or clinical effluent of PD patients, were assessed for O-GlcNAcylation under normal conditions or after exposure to PDF. 24854264 4 86 theme dynamic 804:810 arg1 status 812:817 The dynamic status 800:817 The dynamic status of O-GlcNAcylation and effects on cellular survival 800:869 The dynamic status of O-GlcNAcylation and effects on cellular survival were investigated by chemical modulation with 6-diazo-5-oxo-L-norleucine (DON) to decrease or O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino N-phenyl carbamate (PUGNAc) to increase O-GlcNAc levels. 24854264 1 87 link O-linked 270:277 arg1 O-GlcNAc 300:307 O-GlcNAc 300:307 O-GlcNAc 300:307 The ability of cells to respond and survive stressful conditions is determined, in part, by the attachment of O-linked N-acetylglucosamine (O-GlcNAc) to proteins (O-GlcNAcylation), a post-translational modification dependent on glucose and glutamine. 24854264 1 87 link O-linked 270:277 arg1 N-acetylglucosamine 279:297 O-linked N-acetylglucosamine 270:297 O-linked N-acetylglucosamine (O-GlcNAc) 270:308 The ability of cells to respond and survive stressful conditions is determined, in part, by the attachment of O-linked N-acetylglucosamine (O-GlcNAc) to proteins (O-GlcNAcylation), a post-translational modification dependent on glucose and glutamine. 27432553 2 0 from HPLC 483:486 arg1 release 442:448 release 442:448 release from glycoprotein and subsequent HPLC 442:486 Quantitative characterization of glycomic changes associated with these conditions has been achieved historically by reductive coupling of oligosaccharides to various fluorophores following release from glycoprotein and subsequent HPLC or capillary electrophoretic separation. 27432553 2 0 from HPLC 483:486 arg1 separation 517:526 capillary electrophoretic separation 491:526 capillary electrophoretic separation 491:526 Quantitative characterization of glycomic changes associated with these conditions has been achieved historically by reductive coupling of oligosaccharides to various fluorophores following release from glycoprotein and subsequent HPLC or capillary electrophoretic separation. 27432553 5 1 theme Relative 889:896 arg1 quantification 898:911 Relative quantification 889:911 Relative quantification 889:911 Relative quantification has been valuable for highlighting changes in glycan expression between samples; sensitivity is high, and structural information can be derived by fragmentation. 27432553 4 2 theme signal 766:771 arg1 intensity 773:781 the signal intensity 762:781 the signal intensity for an individual glycan 762:806 Mass spectrometry, on the other hand, has generally been limited to relative quantification in which the contribution of the signal intensity for an individual glycan is expressed as a percent of the signal intensity summed over the total profile. 27432553 8 3 theme glycomic 1552:1559 arg1 analysis 1561:1568 MS-based glycomic analysis 1543:1568 MS-based glycomic analysis 1543:1568 Our results indicate that absolute quantification for MS-based glycomic analysis is reproducible and robust utilizing currently available glycan standards. 27432553 8 4 theme available 1617:1625 arg1 standards 1634:1642 currently available glycan standards 1607:1642 currently available glycan standards 1607:1642 Our results indicate that absolute quantification for MS-based glycomic analysis is reproducible and robust utilizing currently available glycan standards. 27432553 6 5 theme signal 1177:1182 arg1 intensities 1184:1194 signal intensities 1177:1194 signal intensities 1177:1194 We have investigated whether MS-based glycomics is amenable to absolute quantification by referencing signal intensities to well-characterized oligosaccharide standards. 27432553 8 6 theme absolute 1515:1522 arg1 quantification 1524:1537 absolute quantification 1515:1537 absolute quantification for MS-based glycomic analysis 1515:1568 Our results indicate that absolute quantification for MS-based glycomic analysis is reproducible and robust utilizing currently available glycan standards. 27432553 5 7 theme glycan 959:964 arg1 expression 966:975 glycan expression 959:975 glycan expression between samples 959:991 Relative quantification has been valuable for highlighting changes in glycan expression between samples; sensitivity is high, and structural information can be derived by fragmentation. 27432553 7 8 from matrices 1431:1438 arg1 sensitivity 1381:1391 sensitivity 1381:1391 sensitivity 1381:1391 We report the qualification of a set of N-linked oligosaccharide standards by NMR, HPLC, and MS. We also demonstrate the dynamic range, sensitivity, and recovery from complex biological matrices for these standards in their permethylated form. 27432553 7 8 from matrices 1431:1438 arg1 recovery 1398:1405 recovery 1398:1405 recovery from complex biological matrices 1398:1438 We report the qualification of a set of N-linked oligosaccharide standards by NMR, HPLC, and MS. We also demonstrate the dynamic range, sensitivity, and recovery from complex biological matrices for these standards in their permethylated form. 27432553 7 8 from matrices 1431:1438 arg1 range 1374:1378 the dynamic range 1362:1378 the dynamic range 1362:1378 We report the qualification of a set of N-linked oligosaccharide standards by NMR, HPLC, and MS. We also demonstrate the dynamic range, sensitivity, and recovery from complex biological matrices for these standards in their permethylated form. 27432553 4 9 theme other 667:671 arg1 hand 673:676 the other hand 663:676 the other hand 663:676 Mass spectrometry, on the other hand, has generally been limited to relative quantification in which the contribution of the signal intensity for an individual glycan is expressed as a percent of the signal intensity summed over the total profile. 27432553 2 10 gly glycoprotein 455:466 arg1 glycoprotein 455:466 glycoprotein 455:466 glycoprotein 455:466 Quantitative characterization of glycomic changes associated with these conditions has been achieved historically by reductive coupling of oligosaccharides to various fluorophores following release from glycoprotein and subsequent HPLC or capillary electrophoretic separation. 27432553 3 11 theme fluorescence 621:632 arg1 yield 634:638 fluorescence yield 621:638 fluorescence yield 621:638 Such labeling-based approaches provide a robust means of quantifying glycan amount based on fluorescence yield. 27432553 6 12 theme oligosaccharide 1218:1232 arg1 standards 1234:1242 well-characterized oligosaccharide standards 1199:1242 well-characterized oligosaccharide standards 1199:1242 We have investigated whether MS-based glycomics is amenable to absolute quantification by referencing signal intensities to well-characterized oligosaccharide standards. 27432553 7 13 theme oligosaccharide 1294:1308 arg1 standards 1310:1318 N-linked oligosaccharide standards 1285:1318 N-linked oligosaccharide standards 1285:1318 We report the qualification of a set of N-linked oligosaccharide standards by NMR, HPLC, and MS. We also demonstrate the dynamic range, sensitivity, and recovery from complex biological matrices for these standards in their permethylated form. 27432553 7 14 theme set 1278:1280 arg1 qualification 1259:1271 the qualification 1255:1271 the qualification of a set of N-linked oligosaccharide standards by NMR, HPLC, and MS. 1255:1340 We report the qualification of a set of N-linked oligosaccharide standards by NMR, HPLC, and MS. We also demonstrate the dynamic range, sensitivity, and recovery from complex biological matrices for these standards in their permethylated form. 27432553 4 15 from spectrometry 646:657 arg1 hand 673:676 the other hand 663:676 the other hand 663:676 Mass spectrometry, on the other hand, has generally been limited to relative quantification in which the contribution of the signal intensity for an individual glycan is expressed as a percent of the signal intensity summed over the total profile. 27432553 2 16 theme changes 294:300 arg1 characterization 265:280 Quantitative characterization 252:280 Quantitative characterization of glycomic changes associated with these conditions 252:333 Quantitative characterization of glycomic changes associated with these conditions has been achieved historically by reductive coupling of oligosaccharides to various fluorophores following release from glycoprotein and subsequent HPLC or capillary electrophoretic separation. 27432553 7 17 theme biological 1420:1429 arg1 matrices 1431:1438 complex biological matrices 1412:1438 complex biological matrices 1412:1438 We report the qualification of a set of N-linked oligosaccharide standards by NMR, HPLC, and MS. We also demonstrate the dynamic range, sensitivity, and recovery from complex biological matrices for these standards in their permethylated form. 27432553 7 18 theme standards 1310:1318 arg1 set 1278:1280 a set 1276:1280 a set of N-linked oligosaccharide standards 1276:1318 We report the qualification of a set of N-linked oligosaccharide standards by NMR, HPLC, and MS. We also demonstrate the dynamic range, sensitivity, and recovery from complex biological matrices for these standards in their permethylated form. 27432553 7 18 theme standards 1310:1318 arg1 standards 1310:1318 N-linked oligosaccharide standards 1285:1318 N-linked oligosaccharide standards 1285:1318 We report the qualification of a set of N-linked oligosaccharide standards by NMR, HPLC, and MS. We also demonstrate the dynamic range, sensitivity, and recovery from complex biological matrices for these standards in their permethylated form. 27432553 0 19 theme Mass 0:3 arg1 Quantification 19:32 Mass Spectrometric Quantification 0:32 Mass Spectrometric Quantification of N-Linked Glycans by Reference to Exogenous Standards. 0:89 Mass Spectrometric Quantification of N-Linked Glycans by Reference to Exogenous Standards. 27432553 7 20 from standards 1450:1458 arg1 form 1483:1486 their permethylated form 1463:1486 their permethylated form 1463:1486 We report the qualification of a set of N-linked oligosaccharide standards by NMR, HPLC, and MS. We also demonstrate the dynamic range, sensitivity, and recovery from complex biological matrices for these standards in their permethylated form. 27432553 0 21 theme Spectrometric 5:17 arg1 Quantification 19:32 Mass Spectrometric Quantification 0:32 Mass Spectrometric Quantification of N-Linked Glycans by Reference to Exogenous Standards. 0:89 Mass Spectrometric Quantification of N-Linked Glycans by Reference to Exogenous Standards. 27432553 3 22 theme glycan 598:603 arg1 amount 605:610 glycan amount 598:610 glycan amount 598:610 Such labeling-based approaches provide a robust means of quantifying glycan amount based on fluorescence yield. 27432553 1 23 theme Environmental 91:103 arg1 processes 119:127 Environmental and metabolic processes 91:127 Environmental and metabolic processes 91:127 Environmental and metabolic processes shape the profile of glycoprotein glycans expressed by cells, whether in culture, developing tissues, or mature organisms. 27432553 7 24 theme dynamic 1366:1372 arg1 range 1374:1378 the dynamic range 1362:1378 the dynamic range 1362:1378 We report the qualification of a set of N-linked oligosaccharide standards by NMR, HPLC, and MS. We also demonstrate the dynamic range, sensitivity, and recovery from complex biological matrices for these standards in their permethylated form. 27432553 2 25 theme capillary 491:499 arg1 separation 517:526 capillary electrophoretic separation 491:526 capillary electrophoretic separation 491:526 Quantitative characterization of glycomic changes associated with these conditions has been achieved historically by reductive coupling of oligosaccharides to various fluorophores following release from glycoprotein and subsequent HPLC or capillary electrophoretic separation. 27432553 2 26 theme various 411:417 arg1 fluorophores 419:430 various fluorophores 411:430 various fluorophores following release from glycoprotein and subsequent HPLC or capillary electrophoretic separation 411:526 Quantitative characterization of glycomic changes associated with these conditions has been achieved historically by reductive coupling of oligosaccharides to various fluorophores following release from glycoprotein and subsequent HPLC or capillary electrophoretic separation. 27432553 8 27 theme MS-based 1543:1550 arg1 analysis 1561:1568 MS-based glycomic analysis 1543:1568 MS-based glycomic analysis 1543:1568 Our results indicate that absolute quantification for MS-based glycomic analysis is reproducible and robust utilizing currently available glycan standards. 27432553 7 28 theme complex 1412:1418 arg1 matrices 1431:1438 complex biological matrices 1412:1438 complex biological matrices 1412:1438 We report the qualification of a set of N-linked oligosaccharide standards by NMR, HPLC, and MS. We also demonstrate the dynamic range, sensitivity, and recovery from complex biological matrices for these standards in their permethylated form. 27432553 1 29 theme metabolic 109:117 arg1 processes 119:127 Environmental and metabolic processes 91:127 Environmental and metabolic processes 91:127 Environmental and metabolic processes shape the profile of glycoprotein glycans expressed by cells, whether in culture, developing tissues, or mature organisms. 27432553 4 30 theme total 874:878 arg1 profile 880:886 the total profile 870:886 the total profile 870:886 Mass spectrometry, on the other hand, has generally been limited to relative quantification in which the contribution of the signal intensity for an individual glycan is expressed as a percent of the signal intensity summed over the total profile. 27432553 2 31 theme subsequent 472:481 arg1 HPLC 483:486 subsequent HPLC 472:486 subsequent HPLC 472:486 Quantitative characterization of glycomic changes associated with these conditions has been achieved historically by reductive coupling of oligosaccharides to various fluorophores following release from glycoprotein and subsequent HPLC or capillary electrophoretic separation. 27432553 5 32 from changes 948:954 arg1 expression 966:975 glycan expression 959:975 glycan expression between samples 959:991 Relative quantification has been valuable for highlighting changes in glycan expression between samples; sensitivity is high, and structural information can be derived by fragmentation. 27432553 5 33 theme structural 1019:1028 arg1 information 1030:1040 structural information 1019:1040 structural information 1019:1040 Relative quantification has been valuable for highlighting changes in glycan expression between samples; sensitivity is high, and structural information can be derived by fragmentation. 27432553 3 34 theme labeling-based 534:547 arg1 approaches 549:558 Such labeling-based approaches 529:558 Such labeling-based approaches 529:558 Such labeling-based approaches provide a robust means of quantifying glycan amount based on fluorescence yield. 27432553 0 35 theme Glycans 46:52 arg1 Quantification 19:32 Mass Spectrometric Quantification 0:32 Mass Spectrometric Quantification of N-Linked Glycans by Reference to Exogenous Standards. 0:89 Mass Spectrometric Quantification of N-Linked Glycans by Reference to Exogenous Standards. 27432553 4 36 theme Mass 641:644 arg1 spectrometry 646:657 Mass spectrometry 641:657 Mass spectrometry 641:657 Mass spectrometry, on the other hand, has generally been limited to relative quantification in which the contribution of the signal intensity for an individual glycan is expressed as a percent of the signal intensity summed over the total profile. 27432553 4 37 theme relative 709:716 arg1 quantification 718:731 relative quantification 709:731 relative quantification in which the contribution of the signal intensity for an individual glycan is expressed as a percent of the signal intensity summed over the total profile 709:886 Mass spectrometry, on the other hand, has generally been limited to relative quantification in which the contribution of the signal intensity for an individual glycan is expressed as a percent of the signal intensity summed over the total profile. 27432553 1 38 dep whether 191:197 arg1 in 199:200 in 199:200 in 199:200 Environmental and metabolic processes shape the profile of glycoprotein glycans expressed by cells, whether in culture, developing tissues, or mature organisms. 27432553 6 39 theme absolute 1138:1145 arg1 quantification 1147:1160 absolute quantification 1138:1160 absolute quantification 1138:1160 We have investigated whether MS-based glycomics is amenable to absolute quantification by referencing signal intensities to well-characterized oligosaccharide standards. 27432553 1 40 theme developing 211:220 arg1 tissues 222:228 developing tissues 211:228 developing tissues 211:228 Environmental and metabolic processes shape the profile of glycoprotein glycans expressed by cells, whether in culture, developing tissues, or mature organisms. 27432553 0 41 theme N-Linked 37:44 arg1 Glycans 46:52 N-Linked Glycans 37:52 N-Linked Glycans 37:52 Mass Spectrometric Quantification of N-Linked Glycans by Reference to Exogenous Standards. 27432553 6 42 theme well-characterized 1199:1216 arg1 standards 1234:1242 well-characterized oligosaccharide standards 1199:1242 well-characterized oligosaccharide standards 1199:1242 We have investigated whether MS-based glycomics is amenable to absolute quantification by referencing signal intensities to well-characterized oligosaccharide standards. 27432553 2 43 theme reductive 369:377 arg1 coupling 379:386 reductive coupling 369:386 reductive coupling of oligosaccharides to various fluorophores following release from glycoprotein and subsequent HPLC or capillary electrophoretic separation 369:526 Quantitative characterization of glycomic changes associated with these conditions has been achieved historically by reductive coupling of oligosaccharides to various fluorophores following release from glycoprotein and subsequent HPLC or capillary electrophoretic separation. 27432553 1 44 gly glycoprotein 150:161 arg1 glycoprotein 150:161 glycoprotein glycans 150:169 glycoprotein glycans expressed by cells, whether in culture, developing tissues, or mature organisms 150:249 Environmental and metabolic processes shape the profile of glycoprotein glycans expressed by cells, whether in culture, developing tissues, or mature organisms. 27432553 7 45 theme permethylated 1469:1481 arg1 form 1483:1486 their permethylated form 1463:1486 their permethylated form 1463:1486 We report the qualification of a set of N-linked oligosaccharide standards by NMR, HPLC, and MS. We also demonstrate the dynamic range, sensitivity, and recovery from complex biological matrices for these standards in their permethylated form. 27432553 3 46 theme robust 570:575 arg1 means 577:581 a robust means 568:581 a robust means of quantifying glycan amount based on fluorescence yield 568:638 Such labeling-based approaches provide a robust means of quantifying glycan amount based on fluorescence yield. 27432553 4 47 theme intensity 848:856 arg1 percent 826:832 a percent 824:832 a percent of the signal intensity summed over the total profile 824:886 Mass spectrometry, on the other hand, has generally been limited to relative quantification in which the contribution of the signal intensity for an individual glycan is expressed as a percent of the signal intensity summed over the total profile. 27432553 4 47 theme intensity 848:856 arg1 contribution 746:757 the contribution 742:757 the contribution of the signal intensity for an individual glycan 742:806 Mass spectrometry, on the other hand, has generally been limited to relative quantification in which the contribution of the signal intensity for an individual glycan is expressed as a percent of the signal intensity summed over the total profile. 27432553 4 48 theme individual 790:799 arg1 glycan 801:806 an individual glycan 787:806 an individual glycan 787:806 Mass spectrometry, on the other hand, has generally been limited to relative quantification in which the contribution of the signal intensity for an individual glycan is expressed as a percent of the signal intensity summed over the total profile. 27432553 6 49 theme MS-based 1104:1111 arg1 glycomics 1113:1121 MS-based glycomics 1104:1121 MS-based glycomics 1104:1121 We have investigated whether MS-based glycomics is amenable to absolute quantification by referencing signal intensities to well-characterized oligosaccharide standards. 27432553 2 50 theme glycomic 285:292 arg1 changes 294:300 glycomic changes 285:300 glycomic changes associated with these conditions 285:333 Quantitative characterization of glycomic changes associated with these conditions has been achieved historically by reductive coupling of oligosaccharides to various fluorophores following release from glycoprotein and subsequent HPLC or capillary electrophoretic separation. 27432553 4 51 theme signal 841:846 arg1 intensity 848:856 the signal intensity 837:856 the signal intensity summed over the total profile 837:886 Mass spectrometry, on the other hand, has generally been limited to relative quantification in which the contribution of the signal intensity for an individual glycan is expressed as a percent of the signal intensity summed over the total profile. 27432553 2 52 from glycoprotein 455:466 arg1 release 442:448 release 442:448 release from glycoprotein and subsequent HPLC 442:486 Quantitative characterization of glycomic changes associated with these conditions has been achieved historically by reductive coupling of oligosaccharides to various fluorophores following release from glycoprotein and subsequent HPLC or capillary electrophoretic separation. 27432553 2 52 from glycoprotein 455:466 arg1 separation 517:526 capillary electrophoretic separation 491:526 capillary electrophoretic separation 491:526 Quantitative characterization of glycomic changes associated with these conditions has been achieved historically by reductive coupling of oligosaccharides to various fluorophores following release from glycoprotein and subsequent HPLC or capillary electrophoretic separation. 27432553 2 53 theme oligosaccharides 391:406 arg1 coupling 379:386 reductive coupling 369:386 reductive coupling of oligosaccharides to various fluorophores following release from glycoprotein and subsequent HPLC or capillary electrophoretic separation 369:526 Quantitative characterization of glycomic changes associated with these conditions has been achieved historically by reductive coupling of oligosaccharides to various fluorophores following release from glycoprotein and subsequent HPLC or capillary electrophoretic separation. 27432553 0 54 theme Exogenous 70:78 arg1 Standards 80:88 Exogenous Standards 70:88 Exogenous Standards 70:88 Mass Spectrometric Quantification of N-Linked Glycans by Reference to Exogenous Standards. 27432553 2 55 theme Quantitative 252:263 arg1 characterization 265:280 Quantitative characterization 252:280 Quantitative characterization of glycomic changes associated with these conditions 252:333 Quantitative characterization of glycomic changes associated with these conditions has been achieved historically by reductive coupling of oligosaccharides to various fluorophores following release from glycoprotein and subsequent HPLC or capillary electrophoretic separation. 27432553 3 56 theme Such 529:532 arg1 approaches 549:558 Such labeling-based approaches 529:558 Such labeling-based approaches 529:558 Such labeling-based approaches provide a robust means of quantifying glycan amount based on fluorescence yield. 27432553 1 57 theme glycoprotein 150:161 arg1 glycans 163:169 glycoprotein glycans 150:169 glycoprotein glycans expressed by cells, whether in culture, developing tissues, or mature organisms 150:249 Environmental and metabolic processes shape the profile of glycoprotein glycans expressed by cells, whether in culture, developing tissues, or mature organisms. 27432553 1 58 theme mature 234:239 arg1 organisms 241:249 mature organisms 234:249 mature organisms 234:249 Environmental and metabolic processes shape the profile of glycoprotein glycans expressed by cells, whether in culture, developing tissues, or mature organisms. 27432553 2 59 theme electrophoretic 501:515 arg1 separation 517:526 capillary electrophoretic separation 491:526 capillary electrophoretic separation 491:526 Quantitative characterization of glycomic changes associated with these conditions has been achieved historically by reductive coupling of oligosaccharides to various fluorophores following release from glycoprotein and subsequent HPLC or capillary electrophoretic separation. 27432553 8 60 theme glycan 1627:1632 arg1 standards 1634:1642 currently available glycan standards 1607:1642 currently available glycan standards 1607:1642 Our results indicate that absolute quantification for MS-based glycomic analysis is reproducible and robust utilizing currently available glycan standards. 27432553 7 61 link N-linked 1285:1292 arg1 standards 1310:1318 N-linked oligosaccharide standards 1285:1318 N-linked oligosaccharide standards 1285:1318 We report the qualification of a set of N-linked oligosaccharide standards by NMR, HPLC, and MS. We also demonstrate the dynamic range, sensitivity, and recovery from complex biological matrices for these standards in their permethylated form. 27432553 1 62 theme glycans 163:169 arg1 profile 139:145 the profile 135:145 the profile of glycoprotein glycans expressed by cells, whether in culture, developing tissues, or mature organisms 135:249 Environmental and metabolic processes shape the profile of glycoprotein glycans expressed by cells, whether in culture, developing tissues, or mature organisms. 27432553 7 63 theme N-linked 1285:1292 arg1 standards 1310:1318 N-linked oligosaccharide standards 1285:1318 N-linked oligosaccharide standards 1285:1318 We report the qualification of a set of N-linked oligosaccharide standards by NMR, HPLC, and MS. We also demonstrate the dynamic range, sensitivity, and recovery from complex biological matrices for these standards in their permethylated form. 27432553 4 64 theme intensity 773:781 arg1 percent 826:832 a percent 824:832 a percent of the signal intensity summed over the total profile 824:886 Mass spectrometry, on the other hand, has generally been limited to relative quantification in which the contribution of the signal intensity for an individual glycan is expressed as a percent of the signal intensity summed over the total profile. 27432553 4 64 theme intensity 773:781 arg1 contribution 746:757 the contribution 742:757 the contribution of the signal intensity for an individual glycan 742:806 Mass spectrometry, on the other hand, has generally been limited to relative quantification in which the contribution of the signal intensity for an individual glycan is expressed as a percent of the signal intensity summed over the total profile. 24092836 8 0 link lipid-linked 1271:1282 arg1 LLO 1301:1303 LLO 1301:1303 LLO 1301:1303 Limited proteolysis experiments revealed a conformational change that is triggered upon interaction of the C-terminal region of PglL with the lipid-linked oligosaccharide (LLO) substrate. 24092836 8 0 link lipid-linked 1271:1282 arg1 oligosaccharide 1284:1298 the lipid-linked oligosaccharide 1267:1298 the lipid-linked oligosaccharide (LLO) substrate 1267:1314 Limited proteolysis experiments revealed a conformational change that is triggered upon interaction of the C-terminal region of PglL with the lipid-linked oligosaccharide (LLO) substrate. 24092836 10 1 theme equivalent 1494:1503 arg1 residue 1509:1515 The equivalent His residue 1490:1515 The equivalent His residue 1490:1515 The equivalent His residue is also essential for WaaL activity, which suggests a common mechanism for both enzymes, and supports the hypothesis that O-glycosylation and lipopolysaccharide (LPS) synthesis are evolutionarily related. 24092836 10 1 theme equivalent 1494:1503 arg1 essential 1525:1533 essential 1525:1533 essential 1525:1533 The equivalent His residue is also essential for WaaL activity, which suggests a common mechanism for both enzymes, and supports the hypothesis that O-glycosylation and lipopolysaccharide (LPS) synthesis are evolutionarily related. 24092836 8 2 with interaction 1217:1227 arg1 substrate 1306:1314 the lipid-linked oligosaccharide (LLO) substrate 1267:1314 the lipid-linked oligosaccharide (LLO) substrate 1267:1314 Limited proteolysis experiments revealed a conformational change that is triggered upon interaction of the C-terminal region of PglL with the lipid-linked oligosaccharide (LLO) substrate. 24092836 0 3 dep in 90:91 arg1 vivo 93:96 vivo 93:96 vivo 93:96 Evaluating the role of conserved amino acids in bacterial O-oligosaccharyltransferases by in vivo, in vitro and limited proteolysis assays. 24092836 7 4 theme different 1058:1066 arg1 enzymes 1068:1074 different enzymes 1058:1074 different enzymes in Neisseria gonorrhoeae and Neisseria meningitidis 1058:1126 Both sites are modified with phosphoglycerol (PG) by different enzymes in Neisseria gonorrhoeae and Neisseria meningitidis. 24092836 8 5 theme proteolysis 1137:1147 arg1 experiments 1149:1159 Limited proteolysis experiments 1129:1159 Limited proteolysis experiments 1129:1159 Limited proteolysis experiments revealed a conformational change that is triggered upon interaction of the C-terminal region of PglL with the lipid-linked oligosaccharide (LLO) substrate. 24092836 4 6 theme conserved 653:661 arg1 residues 674:681 conserved amino acid residues 653:681 conserved amino acid residues in the O-OTases 653:697 In this work, conserved amino acid residues in the O-OTases were replaced with alanine in PglL, the O-OTase of Neisseria meningitidis. 24092836 8 7 theme conformational 1172:1185 arg1 change 1187:1192 a conformational change 1170:1192 a conformational change that is triggered upon interaction of the C-terminal region of PglL with the lipid-linked oligosaccharide (LLO) substrate 1170:1314 Limited proteolysis experiments revealed a conformational change that is triggered upon interaction of the C-terminal region of PglL with the lipid-linked oligosaccharide (LLO) substrate. 24092836 8 8 theme region 1247:1252 arg1 interaction 1217:1227 interaction 1217:1227 interaction of the C-terminal region of PglL with the lipid-linked oligosaccharide (LLO) substrate 1217:1314 Limited proteolysis experiments revealed a conformational change that is triggered upon interaction of the C-terminal region of PglL with the lipid-linked oligosaccharide (LLO) substrate. 24092836 8 9 theme PglL 1257:1260 arg1 region 1247:1252 the C-terminal region 1232:1252 the C-terminal region of PglL 1232:1260 Limited proteolysis experiments revealed a conformational change that is triggered upon interaction of the C-terminal region of PglL with the lipid-linked oligosaccharide (LLO) substrate. 24092836 0 10 theme proteolysis 120:130 arg1 assays 132:137 in vivo, in vitro and limited proteolysis assays 90:137 in vivo, in vitro and limited proteolysis assays 90:137 Evaluating the role of conserved amino acids in bacterial O-oligosaccharyltransferases by in vivo, in vitro and limited proteolysis assays. 24092836 1 11 theme enzymes 221:227 arg1 family 211:216 a growing family 201:216 a growing family of enzymes that catalyze the transfer of a glycan from a lipid carrier to protein acceptors 201:308 Bacterial O-Oligosaccharyltransferases (O-OTases) constitute a growing family of enzymes that catalyze the transfer of a glycan from a lipid carrier to protein acceptors. 24092836 2 12 theme A 560:560 arg1 core 562:565 the lipid A core 550:565 the lipid A core 550:565 O-OTases are inner membrane proteins that display limited sequence similarity, except for the Wzy_C signature domain also present in a predicted periplasmic loop of the WaaL ligase, the enzyme responsible for transferring the O antigen to the lipid A core. 24092836 9 13 dep required 1365:1372 arg1 whereas 1396:1402 whereas 1396:1402 whereas 1396:1402 These experiments showed that Q178 and Y405 are required for optimal function, whereas H349 is essential for activity and plays a critical role in the interaction with LLO. 24092836 8 14 theme oligosaccharide 1284:1298 arg1 substrate 1306:1314 the lipid-linked oligosaccharide (LLO) substrate 1267:1314 the lipid-linked oligosaccharide (LLO) substrate 1267:1314 Limited proteolysis experiments revealed a conformational change that is triggered upon interaction of the C-terminal region of PglL with the lipid-linked oligosaccharide (LLO) substrate. 24092836 4 15 theme acid 669:672 arg1 residues 674:681 conserved amino acid residues 653:681 conserved amino acid residues in the O-OTases 653:697 In this work, conserved amino acid residues in the O-OTases were replaced with alanine in PglL, the O-OTase of Neisseria meningitidis. 24092836 0 16 theme bacterial 48:56 arg1 O-oligosaccharyltransferases 58:85 bacterial O-oligosaccharyltransferases 48:85 bacterial O-oligosaccharyltransferases 48:85 Evaluating the role of conserved amino acids in bacterial O-oligosaccharyltransferases by in vivo, in vitro and limited proteolysis assays. 24092836 3 17 theme O-OTase-dependent 585:601 arg1 glycosylation 603:615 O-OTase-dependent glycosylation 585:615 O-OTase-dependent glycosylation 585:615 The mechanism of O-OTase-dependent glycosylation is poorly understood. 24092836 5 18 theme engineered 857:866 arg1 cells 885:889 engineered Escherichia coli cells 857:889 engineered Escherichia coli cells 857:889 The activity of wild-type PglL and its mutant derivatives were analyzed in vivo in engineered Escherichia coli cells, and in in vitro assays. 24092836 2 19 theme WaaL 480:483 arg1 ligase 485:490 the WaaL ligase 476:490 the WaaL ligase 476:490 O-OTases are inner membrane proteins that display limited sequence similarity, except for the Wzy_C signature domain also present in a predicted periplasmic loop of the WaaL ligase, the enzyme responsible for transferring the O antigen to the lipid A core. 24092836 2 19 theme WaaL 480:483 arg1 enzyme 497:502 the enzyme 493:502 the enzyme responsible for transferring the O antigen to the lipid A core 493:565 O-OTases are inner membrane proteins that display limited sequence similarity, except for the Wzy_C signature domain also present in a predicted periplasmic loop of the WaaL ligase, the enzyme responsible for transferring the O antigen to the lipid A core. 24092836 0 20 from role 15:18 arg1 O-oligosaccharyltransferases 58:85 bacterial O-oligosaccharyltransferases 48:85 bacterial O-oligosaccharyltransferases 48:85 Evaluating the role of conserved amino acids in bacterial O-oligosaccharyltransferases by in vivo, in vitro and limited proteolysis assays. 24092836 5 21 dep in 899:900 arg1 vitro 902:906 vitro 902:906 vitro 902:906 The activity of wild-type PglL and its mutant derivatives were analyzed in vivo in engineered Escherichia coli cells, and in in vitro assays. 24092836 6 22 theme pilin 954:958 arg1 pilin 954:958 pilin 954:958 pilin glycosylated exclusively by PglL in E. coli 954:1002 We identified two additional sites of pilin glycosylated exclusively by PglL in E. coli. 24092836 6 22 theme pilin 954:958 arg1 sites 945:949 two additional sites 930:949 two additional sites of pilin glycosylated exclusively by PglL in E. coli 930:1002 We identified two additional sites of pilin glycosylated exclusively by PglL in E. coli. 24092836 0 23 dep in 99:100 arg1 vitro 102:106 vitro 102:106 vitro 102:106 Evaluating the role of conserved amino acids in bacterial O-oligosaccharyltransferases by in vivo, in vitro and limited proteolysis assays. 24092836 0 24 theme in 99:100 arg1 assays 132:137 in vivo, in vitro and limited proteolysis assays 90:137 in vivo, in vitro and limited proteolysis assays 90:137 Evaluating the role of conserved amino acids in bacterial O-oligosaccharyltransferases by in vivo, in vitro and limited proteolysis assays. 24092836 2 25 from loop 468:471 arg1 present 433:439 present 433:439 present 433:439 O-OTases are inner membrane proteins that display limited sequence similarity, except for the Wzy_C signature domain also present in a predicted periplasmic loop of the WaaL ligase, the enzyme responsible for transferring the O antigen to the lipid A core. 24092836 5 26 dep Escherichia 868:878 arg1 coli 880:883 coli 880:883 coli 880:883 The activity of wild-type PglL and its mutant derivatives were analyzed in vivo in engineered Escherichia coli cells, and in in vitro assays. 24092836 7 27 mod modified 1020:1027 arg3 phosphoglycerol 1034:1048 phosphoglycerol 1034:1048 phosphoglycerol (PG) 1034:1053 Both sites are modified with phosphoglycerol (PG) by different enzymes in Neisseria gonorrhoeae and Neisseria meningitidis. 24092836 7 27 mod modified 1020:1027 arg3 PG 1051:1052 PG 1051:1052 PG 1051:1052 Both sites are modified with phosphoglycerol (PG) by different enzymes in Neisseria gonorrhoeae and Neisseria meningitidis. 24092836 7 27 mod modified 1020:1027 arg3 enzymes 1068:1074 different enzymes 1058:1074 different enzymes in Neisseria gonorrhoeae and Neisseria meningitidis 1058:1126 Both sites are modified with phosphoglycerol (PG) by different enzymes in Neisseria gonorrhoeae and Neisseria meningitidis. 24092836 7 27 mod modified 1020:1027 arg1 sites 1010:1014 Both sites 1005:1014 Both sites 1005:1014 Both sites are modified with phosphoglycerol (PG) by different enzymes in Neisseria gonorrhoeae and Neisseria meningitidis. 24092836 4 28 from alanine 718:724 arg1 PglL 729:732 PglL 729:732 PglL 729:732 In this work, conserved amino acid residues in the O-OTases were replaced with alanine in PglL, the O-OTase of Neisseria meningitidis. 24092836 4 28 from alanine 718:724 arg1 O-OTase 739:745 the O-OTase 735:745 the O-OTase of Neisseria meningitidis 735:771 In this work, conserved amino acid residues in the O-OTases were replaced with alanine in PglL, the O-OTase of Neisseria meningitidis. 24092836 2 29 theme present 433:439 arg1 domain 421:426 the Wzy_C signature domain 401:426 the Wzy_C signature domain also present in a predicted periplasmic loop of the WaaL ligase, the enzyme responsible for transferring the O antigen to the lipid A core 401:565 O-OTases are inner membrane proteins that display limited sequence similarity, except for the Wzy_C signature domain also present in a predicted periplasmic loop of the WaaL ligase, the enzyme responsible for transferring the O antigen to the lipid A core. 24092836 5 30 theme PglL 800:803 arg1 activity 778:785 The activity 774:785 The activity of wild-type PglL and its mutant derivatives 774:830 The activity of wild-type PglL and its mutant derivatives were analyzed in vivo in engineered Escherichia coli cells, and in in vitro assays. 24092836 2 31 theme Wzy_C 405:409 arg1 domain 421:426 the Wzy_C signature domain 401:426 the Wzy_C signature domain also present in a predicted periplasmic loop of the WaaL ligase, the enzyme responsible for transferring the O antigen to the lipid A core 401:565 O-OTases are inner membrane proteins that display limited sequence similarity, except for the Wzy_C signature domain also present in a predicted periplasmic loop of the WaaL ligase, the enzyme responsible for transferring the O antigen to the lipid A core. 24092836 11 32 theme glycoengineering 1884:1899 arg1 vaccines 1907:1914 glycoengineering novel vaccines 1884:1914 glycoengineering novel vaccines 1884:1914 These results contribute to the elucidation of the mechanism of O-OTases, which are promising targets for novel antibiotics and present an enormous potential for glycoengineering novel vaccines and therapeutics. 24092836 0 33 theme conserved 23:31 arg1 acids 39:43 conserved amino acids 23:43 conserved amino acids 23:43 Evaluating the role of conserved amino acids in bacterial O-oligosaccharyltransferases by in vivo, in vitro and limited proteolysis assays. 24092836 1 34 theme protein 292:298 arg1 acceptors 300:308 protein acceptors 292:308 protein acceptors 292:308 Bacterial O-Oligosaccharyltransferases (O-OTases) constitute a growing family of enzymes that catalyze the transfer of a glycan from a lipid carrier to protein acceptors. 24092836 2 35 theme periplasmic 456:466 arg1 loop 468:471 a predicted periplasmic loop 444:471 a predicted periplasmic loop of the WaaL ligase, the enzyme responsible for transferring the O antigen to the lipid A core 444:565 O-OTases are inner membrane proteins that display limited sequence similarity, except for the Wzy_C signature domain also present in a predicted periplasmic loop of the WaaL ligase, the enzyme responsible for transferring the O antigen to the lipid A core. 24092836 6 36 gly glycosylated 960:971 arg1 pilin 954:958 pilin 954:958 pilin glycosylated exclusively by PglL in E. coli 954:1002 We identified two additional sites of pilin glycosylated exclusively by PglL in E. coli. 24092836 0 37 theme acids 39:43 arg1 role 15:18 the role 11:18 the role of conserved amino acids in bacterial O-oligosaccharyltransferases 11:85 Evaluating the role of conserved amino acids in bacterial O-oligosaccharyltransferases by in vivo, in vitro and limited proteolysis assays. 24092836 4 38 theme meningitidis 760:771 arg1 PglL 729:732 PglL 729:732 PglL 729:732 In this work, conserved amino acid residues in the O-OTases were replaced with alanine in PglL, the O-OTase of Neisseria meningitidis. 24092836 4 38 theme meningitidis 760:771 arg1 O-OTase 739:745 the O-OTase 735:745 the O-OTase of Neisseria meningitidis 735:771 In this work, conserved amino acid residues in the O-OTases were replaced with alanine in PglL, the O-OTase of Neisseria meningitidis. 24092836 2 39 theme inner 324:328 arg1 proteins 339:346 inner membrane proteins 324:346 inner membrane proteins that display limited sequence similarity, except for the Wzy_C signature domain also present in a predicted periplasmic loop of the WaaL ligase, the enzyme responsible for transferring the O antigen to the lipid A core 324:565 O-OTases are inner membrane proteins that display limited sequence similarity, except for the Wzy_C signature domain also present in a predicted periplasmic loop of the WaaL ligase, the enzyme responsible for transferring the O antigen to the lipid A core. 24092836 2 39 theme inner 324:328 arg1 O-OTases 311:318 O-OTases 311:318 O-OTases 311:318 O-OTases are inner membrane proteins that display limited sequence similarity, except for the Wzy_C signature domain also present in a predicted periplasmic loop of the WaaL ligase, the enzyme responsible for transferring the O antigen to the lipid A core. 24092836 1 40 theme Bacterial 140:148 arg1 O-OTases 180:187 O-OTases 180:187 O-OTases 180:187 Bacterial O-Oligosaccharyltransferases (O-OTases) constitute a growing family of enzymes that catalyze the transfer of a glycan from a lipid carrier to protein acceptors. 24092836 1 40 theme Bacterial 140:148 arg1 O-Oligosaccharyltransferases 150:177 Bacterial O-Oligosaccharyltransferases 140:177 Bacterial O-Oligosaccharyltransferases (O-OTases) 140:188 Bacterial O-Oligosaccharyltransferases (O-OTases) constitute a growing family of enzymes that catalyze the transfer of a glycan from a lipid carrier to protein acceptors. 24092836 2 41 theme sequence 369:376 arg1 similarity 378:387 limited sequence similarity 361:387 limited sequence similarity 361:387 O-OTases are inner membrane proteins that display limited sequence similarity, except for the Wzy_C signature domain also present in a predicted periplasmic loop of the WaaL ligase, the enzyme responsible for transferring the O antigen to the lipid A core. 24092836 10 42 theme His 1505:1507 arg1 residue 1509:1515 The equivalent His residue 1490:1515 The equivalent His residue 1490:1515 The equivalent His residue is also essential for WaaL activity, which suggests a common mechanism for both enzymes, and supports the hypothesis that O-glycosylation and lipopolysaccharide (LPS) synthesis are evolutionarily related. 24092836 10 42 theme His 1505:1507 arg1 essential 1525:1533 essential 1525:1533 essential 1525:1533 The equivalent His residue is also essential for WaaL activity, which suggests a common mechanism for both enzymes, and supports the hypothesis that O-glycosylation and lipopolysaccharide (LPS) synthesis are evolutionarily related. 24092836 11 43 theme novel 1828:1832 arg1 antibiotics 1834:1844 novel antibiotics 1828:1844 novel antibiotics 1828:1844 These results contribute to the elucidation of the mechanism of O-OTases, which are promising targets for novel antibiotics and present an enormous potential for glycoengineering novel vaccines and therapeutics. 24092836 4 44 from residues 674:681 arg1 O-OTases 690:697 the O-OTases 686:697 the O-OTases 686:697 In this work, conserved amino acid residues in the O-OTases were replaced with alanine in PglL, the O-OTase of Neisseria meningitidis. 24092836 10 45 theme WaaL 1539:1542 arg1 activity 1544:1551 WaaL activity 1539:1551 WaaL activity 1539:1551 The equivalent His residue is also essential for WaaL activity, which suggests a common mechanism for both enzymes, and supports the hypothesis that O-glycosylation and lipopolysaccharide (LPS) synthesis are evolutionarily related. 24092836 1 46 theme glycan 261:266 arg1 transfer 247:254 the transfer 243:254 the transfer of a glycan from a lipid carrier to protein acceptors 243:308 Bacterial O-Oligosaccharyltransferases (O-OTases) constitute a growing family of enzymes that catalyze the transfer of a glycan from a lipid carrier to protein acceptors. 24092836 1 47 from carrier 281:287 arg1 transfer 247:254 the transfer 243:254 the transfer of a glycan from a lipid carrier to protein acceptors 243:308 Bacterial O-Oligosaccharyltransferases (O-OTases) constitute a growing family of enzymes that catalyze the transfer of a glycan from a lipid carrier to protein acceptors. 24092836 8 48 theme Limited 1129:1135 arg1 experiments 1149:1159 Limited proteolysis experiments 1129:1159 Limited proteolysis experiments 1129:1159 Limited proteolysis experiments revealed a conformational change that is triggered upon interaction of the C-terminal region of PglL with the lipid-linked oligosaccharide (LLO) substrate. 24092836 6 49 theme additional 934:943 arg1 pilin 954:958 pilin 954:958 pilin glycosylated exclusively by PglL in E. coli 954:1002 We identified two additional sites of pilin glycosylated exclusively by PglL in E. coli. 24092836 6 49 theme additional 934:943 arg1 sites 945:949 two additional sites 930:949 two additional sites of pilin glycosylated exclusively by PglL in E. coli 930:1002 We identified two additional sites of pilin glycosylated exclusively by PglL in E. coli. 24092836 11 50 theme mechanism 1773:1781 arg1 elucidation 1754:1764 the elucidation 1750:1764 the elucidation of the mechanism of O-OTases, which are promising targets for novel antibiotics and present an enormous potential for glycoengineering novel vaccines and therapeutics 1750:1931 These results contribute to the elucidation of the mechanism of O-OTases, which are promising targets for novel antibiotics and present an enormous potential for glycoengineering novel vaccines and therapeutics. 24092836 0 51 theme limited 112:118 arg1 assays 132:137 in vivo, in vitro and limited proteolysis assays 90:137 in vivo, in vitro and limited proteolysis assays 90:137 Evaluating the role of conserved amino acids in bacterial O-oligosaccharyltransferases by in vivo, in vitro and limited proteolysis assays. 24092836 1 52 theme growing 203:209 arg1 family 211:216 a growing family 201:216 a growing family of enzymes that catalyze the transfer of a glycan from a lipid carrier to protein acceptors 201:308 Bacterial O-Oligosaccharyltransferases (O-OTases) constitute a growing family of enzymes that catalyze the transfer of a glycan from a lipid carrier to protein acceptors. 24092836 2 53 theme O 537:537 arg1 antigen 539:545 the O antigen 533:545 the O antigen 533:545 O-OTases are inner membrane proteins that display limited sequence similarity, except for the Wzy_C signature domain also present in a predicted periplasmic loop of the WaaL ligase, the enzyme responsible for transferring the O antigen to the lipid A core. 24092836 8 54 theme C-terminal 1236:1245 arg1 region 1247:1252 the C-terminal region 1232:1252 the C-terminal region of PglL 1232:1260 Limited proteolysis experiments revealed a conformational change that is triggered upon interaction of the C-terminal region of PglL with the lipid-linked oligosaccharide (LLO) substrate. 24092836 2 55 theme membrane 330:337 arg1 proteins 339:346 inner membrane proteins 324:346 inner membrane proteins that display limited sequence similarity, except for the Wzy_C signature domain also present in a predicted periplasmic loop of the WaaL ligase, the enzyme responsible for transferring the O antigen to the lipid A core 324:565 O-OTases are inner membrane proteins that display limited sequence similarity, except for the Wzy_C signature domain also present in a predicted periplasmic loop of the WaaL ligase, the enzyme responsible for transferring the O antigen to the lipid A core. 24092836 2 55 theme membrane 330:337 arg1 O-OTases 311:318 O-OTases 311:318 O-OTases 311:318 O-OTases are inner membrane proteins that display limited sequence similarity, except for the Wzy_C signature domain also present in a predicted periplasmic loop of the WaaL ligase, the enzyme responsible for transferring the O antigen to the lipid A core. 24092836 5 56 theme mutant 813:818 arg1 derivatives 820:830 its mutant derivatives 809:830 its mutant derivatives 809:830 The activity of wild-type PglL and its mutant derivatives were analyzed in vivo in engineered Escherichia coli cells, and in in vitro assays. 24092836 10 57 theme common 1571:1576 arg1 mechanism 1578:1586 a common mechanism 1569:1586 a common mechanism for both enzymes 1569:1603 The equivalent His residue is also essential for WaaL activity, which suggests a common mechanism for both enzymes, and supports the hypothesis that O-glycosylation and lipopolysaccharide (LPS) synthesis are evolutionarily related. 24092836 2 58 theme lipid 554:558 arg1 core 562:565 the lipid A core 550:565 the lipid A core 550:565 O-OTases are inner membrane proteins that display limited sequence similarity, except for the Wzy_C signature domain also present in a predicted periplasmic loop of the WaaL ligase, the enzyme responsible for transferring the O antigen to the lipid A core. 24092836 11 59 theme O-OTases 1786:1793 arg1 mechanism 1773:1781 the mechanism 1769:1781 the mechanism of O-OTases, which are promising targets for novel antibiotics and present an enormous potential for glycoengineering novel vaccines and therapeutics 1769:1931 These results contribute to the elucidation of the mechanism of O-OTases, which are promising targets for novel antibiotics and present an enormous potential for glycoengineering novel vaccines and therapeutics. 24092836 3 60 theme glycosylation 603:615 arg1 mechanism 572:580 The mechanism 568:580 The mechanism of O-OTase-dependent glycosylation 568:615 The mechanism of O-OTase-dependent glycosylation is poorly understood. 24092836 8 61 theme lipid-linked 1271:1282 arg1 LLO 1301:1303 LLO 1301:1303 LLO 1301:1303 Limited proteolysis experiments revealed a conformational change that is triggered upon interaction of the C-terminal region of PglL with the lipid-linked oligosaccharide (LLO) substrate. 24092836 8 61 theme lipid-linked 1271:1282 arg1 oligosaccharide 1284:1298 the lipid-linked oligosaccharide 1267:1298 the lipid-linked oligosaccharide (LLO) substrate 1267:1314 Limited proteolysis experiments revealed a conformational change that is triggered upon interaction of the C-terminal region of PglL with the lipid-linked oligosaccharide (LLO) substrate. 24092836 2 62 theme ligase 485:490 arg1 loop 468:471 a predicted periplasmic loop 444:471 a predicted periplasmic loop of the WaaL ligase, the enzyme responsible for transferring the O antigen to the lipid A core 444:565 O-OTases are inner membrane proteins that display limited sequence similarity, except for the Wzy_C signature domain also present in a predicted periplasmic loop of the WaaL ligase, the enzyme responsible for transferring the O antigen to the lipid A core. 24092836 2 63 from present 433:439 arg1 loop 468:471 a predicted periplasmic loop 444:471 a predicted periplasmic loop of the WaaL ligase, the enzyme responsible for transferring the O antigen to the lipid A core 444:565 O-OTases are inner membrane proteins that display limited sequence similarity, except for the Wzy_C signature domain also present in a predicted periplasmic loop of the WaaL ligase, the enzyme responsible for transferring the O antigen to the lipid A core. 24092836 4 64 theme amino 663:667 arg1 residues 674:681 conserved amino acid residues 653:681 conserved amino acid residues in the O-OTases 653:697 In this work, conserved amino acid residues in the O-OTases were replaced with alanine in PglL, the O-OTase of Neisseria meningitidis. 24092836 0 65 theme in 90:91 arg1 assays 132:137 in vivo, in vitro and limited proteolysis assays 90:137 in vivo, in vitro and limited proteolysis assays 90:137 Evaluating the role of conserved amino acids in bacterial O-oligosaccharyltransferases by in vivo, in vitro and limited proteolysis assays. 24092836 5 66 theme Escherichia 868:878 arg1 cells 885:889 engineered Escherichia coli cells 857:889 engineered Escherichia coli cells 857:889 The activity of wild-type PglL and its mutant derivatives were analyzed in vivo in engineered Escherichia coli cells, and in in vitro assays. 24092836 2 67 theme responsible 504:514 arg1 ligase 485:490 the WaaL ligase 476:490 the WaaL ligase 476:490 O-OTases are inner membrane proteins that display limited sequence similarity, except for the Wzy_C signature domain also present in a predicted periplasmic loop of the WaaL ligase, the enzyme responsible for transferring the O antigen to the lipid A core. 24092836 2 67 theme responsible 504:514 arg1 enzyme 497:502 the enzyme 493:502 the enzyme responsible for transferring the O antigen to the lipid A core 493:565 O-OTases are inner membrane proteins that display limited sequence similarity, except for the Wzy_C signature domain also present in a predicted periplasmic loop of the WaaL ligase, the enzyme responsible for transferring the O antigen to the lipid A core. 24092836 9 68 with interaction 1468:1478 arg1 LLO 1485:1487 LLO 1485:1487 LLO 1485:1487 These experiments showed that Q178 and Y405 are required for optimal function, whereas H349 is essential for activity and plays a critical role in the interaction with LLO. 24092836 5 69 theme in 899:900 arg1 assays 908:913 in vitro assays 899:913 in vitro assays 899:913 The activity of wild-type PglL and its mutant derivatives were analyzed in vivo in engineered Escherichia coli cells, and in in vitro assays. 24092836 11 70 theme enormous 1861:1868 arg1 potential 1870:1878 an enormous potential 1858:1878 an enormous potential for glycoengineering novel vaccines and therapeutics 1858:1931 These results contribute to the elucidation of the mechanism of O-OTases, which are promising targets for novel antibiotics and present an enormous potential for glycoengineering novel vaccines and therapeutics. 24092836 5 71 theme wild-type 790:798 arg1 PglL 800:803 wild-type PglL 790:803 wild-type PglL 790:803 The activity of wild-type PglL and its mutant derivatives were analyzed in vivo in engineered Escherichia coli cells, and in in vitro assays. 24092836 1 72 theme lipid 275:279 arg1 carrier 281:287 a lipid carrier 273:287 a lipid carrier 273:287 Bacterial O-Oligosaccharyltransferases (O-OTases) constitute a growing family of enzymes that catalyze the transfer of a glycan from a lipid carrier to protein acceptors. 24092836 2 73 attach present 433:439 arg2 domain 421:426 the Wzy_C signature domain 401:426 the Wzy_C signature domain also present in a predicted periplasmic loop of the WaaL ligase, the enzyme responsible for transferring the O antigen to the lipid A core 401:565 O-OTases are inner membrane proteins that display limited sequence similarity, except for the Wzy_C signature domain also present in a predicted periplasmic loop of the WaaL ligase, the enzyme responsible for transferring the O antigen to the lipid A core. 24092836 2 73 attach present 433:439 arg1 loop 468:471 a predicted periplasmic loop 444:471 a predicted periplasmic loop of the WaaL ligase, the enzyme responsible for transferring the O antigen to the lipid A core 444:565 O-OTases are inner membrane proteins that display limited sequence similarity, except for the Wzy_C signature domain also present in a predicted periplasmic loop of the WaaL ligase, the enzyme responsible for transferring the O antigen to the lipid A core. 24092836 2 74 theme signature 411:419 arg1 domain 421:426 the Wzy_C signature domain 401:426 the Wzy_C signature domain also present in a predicted periplasmic loop of the WaaL ligase, the enzyme responsible for transferring the O antigen to the lipid A core 401:565 O-OTases are inner membrane proteins that display limited sequence similarity, except for the Wzy_C signature domain also present in a predicted periplasmic loop of the WaaL ligase, the enzyme responsible for transferring the O antigen to the lipid A core. 24092836 0 75 theme amino 33:37 arg1 acids 39:43 conserved amino acids 23:43 conserved amino acids 23:43 Evaluating the role of conserved amino acids in bacterial O-oligosaccharyltransferases by in vivo, in vitro and limited proteolysis assays. 24092836 5 76 theme derivatives 820:830 arg1 activity 778:785 The activity 774:785 The activity of wild-type PglL and its mutant derivatives 774:830 The activity of wild-type PglL and its mutant derivatives were analyzed in vivo in engineered Escherichia coli cells, and in in vitro assays. 24092836 11 77 theme novel 1901:1905 arg1 vaccines 1907:1914 glycoengineering novel vaccines 1884:1914 glycoengineering novel vaccines 1884:1914 These results contribute to the elucidation of the mechanism of O-OTases, which are promising targets for novel antibiotics and present an enormous potential for glycoengineering novel vaccines and therapeutics. 24092836 2 78 theme predicted 446:454 arg1 loop 468:471 a predicted periplasmic loop 444:471 a predicted periplasmic loop of the WaaL ligase, the enzyme responsible for transferring the O antigen to the lipid A core 444:565 O-OTases are inner membrane proteins that display limited sequence similarity, except for the Wzy_C signature domain also present in a predicted periplasmic loop of the WaaL ligase, the enzyme responsible for transferring the O antigen to the lipid A core. 24092836 7 79 from enzymes 1068:1074 arg1 gonorrhoeae 1089:1099 Neisseria gonorrhoeae 1079:1099 Neisseria gonorrhoeae 1079:1099 Both sites are modified with phosphoglycerol (PG) by different enzymes in Neisseria gonorrhoeae and Neisseria meningitidis. 24092836 7 79 from enzymes 1068:1074 arg1 meningitidis 1115:1126 Neisseria meningitidis 1105:1126 Neisseria meningitidis 1105:1126 Both sites are modified with phosphoglycerol (PG) by different enzymes in Neisseria gonorrhoeae and Neisseria meningitidis. 24092836 10 80 theme lipopolysaccharide 1659:1676 arg1 synthesis 1684:1692 lipopolysaccharide (LPS) synthesis 1659:1692 lipopolysaccharide (LPS) synthesis 1659:1692 The equivalent His residue is also essential for WaaL activity, which suggests a common mechanism for both enzymes, and supports the hypothesis that O-glycosylation and lipopolysaccharide (LPS) synthesis are evolutionarily related. 24092836 4 81 theme Neisseria 750:758 arg1 meningitidis 760:771 Neisseria meningitidis 750:771 Neisseria meningitidis 750:771 In this work, conserved amino acid residues in the O-OTases were replaced with alanine in PglL, the O-OTase of Neisseria meningitidis. 24092836 11 82 theme promising 1806:1814 arg1 targets 1816:1822 promising targets 1806:1822 promising targets for novel antibiotics 1806:1844 These results contribute to the elucidation of the mechanism of O-OTases, which are promising targets for novel antibiotics and present an enormous potential for glycoengineering novel vaccines and therapeutics. 24092836 11 82 theme promising 1806:1814 arg1 O-OTases 1786:1793 O-OTases 1786:1793 O-OTases 1786:1793 These results contribute to the elucidation of the mechanism of O-OTases, which are promising targets for novel antibiotics and present an enormous potential for glycoengineering novel vaccines and therapeutics. 24092836 9 83 theme critical 1447:1454 arg1 role 1456:1459 a critical role 1445:1459 a critical role 1445:1459 These experiments showed that Q178 and Y405 are required for optimal function, whereas H349 is essential for activity and plays a critical role in the interaction with LLO. 24092836 2 84 theme limited 361:367 arg1 similarity 378:387 limited sequence similarity 361:387 limited sequence similarity 361:387 O-OTases are inner membrane proteins that display limited sequence similarity, except for the Wzy_C signature domain also present in a predicted periplasmic loop of the WaaL ligase, the enzyme responsible for transferring the O antigen to the lipid A core. 24092836 9 85 theme optimal 1378:1384 arg1 function 1386:1393 optimal function 1378:1393 optimal function 1378:1393 These experiments showed that Q178 and Y405 are required for optimal function, whereas H349 is essential for activity and plays a critical role in the interaction with LLO. 28472687 0 0 theme Dioscorea 90:98 arg1 bulbils 110:116 Dioscorea bulbifera bulbils 90:116 Dioscorea bulbifera bulbils 90:116 Purification, characterization and biological significance of mannose binding lectin from Dioscorea bulbifera bulbils. 28472687 2 1 theme cancer 458:463 arg1 research 473:480 cancer and HIV research 458:480 research 473:480 A mannose binding lectin from bulbils of D. bulbifera was purified in a single step by affinity chromatography on mucin coupled Sepharose 4B column, determined by its fine sugar specificity by glycan array analysis and studied for its clinical potential in cancer and HIV research. 28472687 7 2 theme dependent 1096:1104 arg1 effects 1124:1130 dose and time dependent growth inhibitory effects 1082:1130 dose and time dependent growth inhibitory effects on all the three cell lines HT 29, SW 620 and HepG2 1082:1182 DBL showed dose and time dependent growth inhibitory effects on all the three cell lines HT 29, SW 620 and HepG2 with IC50 of 110μg, 9.8μg, 40μg respectively at 72h. 28472687 2 3 theme 4B 339:340 arg1 column 342:347 mucin coupled Sepharose 4B column 315:347 mucin coupled Sepharose 4B column 315:347 A mannose binding lectin from bulbils of D. bulbifera was purified in a single step by affinity chromatography on mucin coupled Sepharose 4B column, determined by its fine sugar specificity by glycan array analysis and studied for its clinical potential in cancer and HIV research. 28472687 6 4 theme epithelial 991:1000 arg1 cancer 1002:1007 non-metastatic human colon epithelial cancer HT 29 964:1013 non-metastatic human colon epithelial cancer HT 29 964:1013 DBL showed strong binding to non-metastatic human colon epithelial cancer HT 29, metastatic SW 620 and hepatocellular HepG2 cell lines. 28472687 7 5 from effects 1124:1130 arg1 HT 1160:1161 HT 29 1160:1164 HT 29 1160:1164 DBL showed dose and time dependent growth inhibitory effects on all the three cell lines HT 29, SW 620 and HepG2 with IC50 of 110μg, 9.8μg, 40μg respectively at 72h. 28472687 7 5 from effects 1124:1130 arg1 SW 1167:1168 SW 620 1167:1172 SW 620 1167:1172 DBL showed dose and time dependent growth inhibitory effects on all the three cell lines HT 29, SW 620 and HepG2 with IC50 of 110μg, 9.8μg, 40μg respectively at 72h. 28472687 7 5 from effects 1124:1130 arg1 HepG2 1178:1182 HepG2 1178:1182 HepG2 1178:1182 DBL showed dose and time dependent growth inhibitory effects on all the three cell lines HT 29, SW 620 and HepG2 with IC50 of 110μg, 9.8μg, 40μg respectively at 72h. 28472687 7 5 from effects 1124:1130 arg1 lines 1154:1158 the three cell lines 1139:1158 all the three cell lines HT 29, SW 620 and HepG2 1135:1182 DBL showed dose and time dependent growth inhibitory effects on all the three cell lines HT 29, SW 620 and HepG2 with IC50 of 110μg, 9.8μg, 40μg respectively at 72h. 28472687 7 6 theme growth 1106:1111 arg1 effects 1124:1130 dose and time dependent growth inhibitory effects 1082:1130 dose and time dependent growth inhibitory effects on all the three cell lines HT 29, SW 620 and HepG2 1082:1182 DBL showed dose and time dependent growth inhibitory effects on all the three cell lines HT 29, SW 620 and HepG2 with IC50 of 110μg, 9.8μg, 40μg respectively at 72h. 28472687 5 7 theme glycoprotein 864:875 arg1 gp120 877:881 HIV envelope glycoprotein gp120 851:881 HIV envelope glycoprotein gp120 851:881 Glycan array analysis of DBL revealed its affinity toward high mannose N-linked glycans with enhanced affinity for terminal mannose including N-linked glycans of HIV envelope glycoprotein gp120 and has strong anti-reverse transcriptase activity. 28472687 2 8 theme Sepharose 329:337 arg1 column 342:347 mucin coupled Sepharose 4B column 315:347 mucin coupled Sepharose 4B column 315:347 A mannose binding lectin from bulbils of D. bulbifera was purified in a single step by affinity chromatography on mucin coupled Sepharose 4B column, determined by its fine sugar specificity by glycan array analysis and studied for its clinical potential in cancer and HIV research. 28472687 6 9 theme colon 985:989 arg1 cancer 1002:1007 non-metastatic human colon epithelial cancer HT 29 964:1013 non-metastatic human colon epithelial cancer HT 29 964:1013 DBL showed strong binding to non-metastatic human colon epithelial cancer HT 29, metastatic SW 620 and hepatocellular HepG2 cell lines. 28472687 8 10 theme glycans 1311:1317 arg1 presence 1289:1296 presence 1289:1296 presence of competing glycans like mucin 1289:1328 Inhibitory effect of DBL was effectively blocked in presence of competing glycans like mucin. 28472687 2 11 from chromatography 297:310 arg1 column 342:347 mucin coupled Sepharose 4B column 315:347 mucin coupled Sepharose 4B column 315:347 A mannose binding lectin from bulbils of D. bulbifera was purified in a single step by affinity chromatography on mucin coupled Sepharose 4B column, determined by its fine sugar specificity by glycan array analysis and studied for its clinical potential in cancer and HIV research. 28472687 9 12 contain has 1335:1337 arg1 DBL 1331:1333 DBL 1331:1333 DBL 1331:1333 DBL has promising clinical potential both in cancer and HIV research. 28472687 9 12 contain has 1335:1337 arg2 potential 1358:1366 promising clinical potential 1339:1366 promising clinical potential 1339:1366 DBL has promising clinical potential both in cancer and HIV research. 28472687 2 13 theme single 273:278 arg1 step 280:283 a single step 271:283 a single step 271:283 A mannose binding lectin from bulbils of D. bulbifera was purified in a single step by affinity chromatography on mucin coupled Sepharose 4B column, determined by its fine sugar specificity by glycan array analysis and studied for its clinical potential in cancer and HIV research. 28472687 6 14 theme human 979:983 arg1 cancer 1002:1007 non-metastatic human colon epithelial cancer HT 29 964:1013 non-metastatic human colon epithelial cancer HT 29 964:1013 DBL showed strong binding to non-metastatic human colon epithelial cancer HT 29, metastatic SW 620 and hepatocellular HepG2 cell lines. 28472687 0 15 theme bulbifera 100:108 arg1 bulbils 110:116 Dioscorea bulbifera bulbils 90:116 Dioscorea bulbifera bulbils 90:116 Purification, characterization and biological significance of mannose binding lectin from Dioscorea bulbifera bulbils. 28472687 7 16 theme time 1091:1094 arg1 effects 1124:1130 dose and time dependent growth inhibitory effects 1082:1130 dose and time dependent growth inhibitory effects on all the three cell lines HT 29, SW 620 and HepG2 1082:1182 DBL showed dose and time dependent growth inhibitory effects on all the three cell lines HT 29, SW 620 and HepG2 with IC50 of 110μg, 9.8μg, 40μg respectively at 72h. 28472687 1 17 used used 162:165 arg2 bulbifera 129:137 Dioscorea bulbifera 119:137 Dioscorea bulbifera 119:137 Dioscorea bulbifera or air potato has been used as a folk remedy to treat cancer. 28472687 1 17 used used 162:165 arg2 potato 146:151 air potato 142:151 air potato 142:151 Dioscorea bulbifera or air potato has been used as a folk remedy to treat cancer. 28472687 1 17 used used 162:165 arg2 remedy 177:182 a folk remedy 170:182 a folk remedy 170:182 Dioscorea bulbifera or air potato has been used as a folk remedy to treat cancer. 28472687 6 18 theme non-metastatic 964:977 arg1 cancer 1002:1007 non-metastatic human colon epithelial cancer HT 29 964:1013 non-metastatic human colon epithelial cancer HT 29 964:1013 DBL showed strong binding to non-metastatic human colon epithelial cancer HT 29, metastatic SW 620 and hepatocellular HepG2 cell lines. 28472687 5 19 theme array 696:700 arg1 analysis 702:709 Glycan array analysis 689:709 Glycan array analysis of DBL 689:716 Glycan array analysis of DBL revealed its affinity toward high mannose N-linked glycans with enhanced affinity for terminal mannose including N-linked glycans of HIV envelope glycoprotein gp120 and has strong anti-reverse transcriptase activity. 28472687 5 20 theme strong 891:896 arg1 transcriptase 911:923 strong anti-reverse transcriptase 891:923 strong anti-reverse transcriptase activity 891:932 Glycan array analysis of DBL revealed its affinity toward high mannose N-linked glycans with enhanced affinity for terminal mannose including N-linked glycans of HIV envelope glycoprotein gp120 and has strong anti-reverse transcriptase activity. 28472687 2 21 theme fine 368:371 arg1 specificity 379:389 its fine sugar specificity 364:389 its fine sugar specificity 364:389 A mannose binding lectin from bulbils of D. bulbifera was purified in a single step by affinity chromatography on mucin coupled Sepharose 4B column, determined by its fine sugar specificity by glycan array analysis and studied for its clinical potential in cancer and HIV research. 28472687 7 22 theme inhibitory 1113:1122 arg1 effects 1124:1130 dose and time dependent growth inhibitory effects 1082:1130 dose and time dependent growth inhibitory effects on all the three cell lines HT 29, SW 620 and HepG2 1082:1182 DBL showed dose and time dependent growth inhibitory effects on all the three cell lines HT 29, SW 620 and HepG2 with IC50 of 110μg, 9.8μg, 40μg respectively at 72h. 28472687 5 23 theme gp120 877:881 arg1 glycans 840:846 N-linked glycans 831:846 N-linked glycans of HIV envelope glycoprotein gp120 831:881 Glycan array analysis of DBL revealed its affinity toward high mannose N-linked glycans with enhanced affinity for terminal mannose including N-linked glycans of HIV envelope glycoprotein gp120 and has strong anti-reverse transcriptase activity. 28472687 9 24 theme promising 1339:1347 arg1 potential 1358:1366 promising clinical potential 1339:1366 promising clinical potential 1339:1366 DBL has promising clinical potential both in cancer and HIV research. 28472687 5 25 theme transcriptase 911:923 arg1 activity 925:932 strong anti-reverse transcriptase activity 891:932 strong anti-reverse transcriptase activity 891:932 Glycan array analysis of DBL revealed its affinity toward high mannose N-linked glycans with enhanced affinity for terminal mannose including N-linked glycans of HIV envelope glycoprotein gp120 and has strong anti-reverse transcriptase activity. 28472687 7 26 dep showed 1075:1080 arg1 40μg 1211:1214 40μg 1211:1214 40μg respectively at 72h 1211:1234 DBL showed dose and time dependent growth inhibitory effects on all the three cell lines HT 29, SW 620 and HepG2 with IC50 of 110μg, 9.8μg, 40μg respectively at 72h. 28472687 1 27 theme folk 172:175 arg1 remedy 177:182 a folk remedy 170:182 a folk remedy 170:182 Dioscorea bulbifera or air potato has been used as a folk remedy to treat cancer. 28472687 1 27 theme folk 172:175 arg1 bulbifera 129:137 Dioscorea bulbifera 119:137 Dioscorea bulbifera 119:137 Dioscorea bulbifera or air potato has been used as a folk remedy to treat cancer. 28472687 1 27 theme folk 172:175 arg1 potato 146:151 air potato 142:151 air potato 142:151 Dioscorea bulbifera or air potato has been used as a folk remedy to treat cancer. 28472687 5 28 theme N-linked 760:767 arg1 glycans 769:775 high mannose N-linked glycans 747:775 high mannose N-linked glycans 747:775 Glycan array analysis of DBL revealed its affinity toward high mannose N-linked glycans with enhanced affinity for terminal mannose including N-linked glycans of HIV envelope glycoprotein gp120 and has strong anti-reverse transcriptase activity. 28472687 0 29 theme lectin 78:83 arg1 characterization 14:29 characterization 14:29 characterization 14:29 Purification, characterization and biological significance of mannose binding lectin from Dioscorea bulbifera bulbils. 28472687 0 29 theme lectin 78:83 arg1 significance 46:57 biological significance 35:57 biological significance 35:57 Purification, characterization and biological significance of mannose binding lectin from Dioscorea bulbifera bulbils. 28472687 0 29 theme lectin 78:83 arg1 Purification 0:11 Purification 0:11 Purification 0:11 Purification, characterization and biological significance of mannose binding lectin from Dioscorea bulbifera bulbils. 28472687 2 30 theme affinity 288:295 arg1 chromatography 297:310 affinity chromatography 288:310 affinity chromatography on mucin coupled Sepharose 4B column, determined by its fine sugar specificity by glycan array analysis 288:414 A mannose binding lectin from bulbils of D. bulbifera was purified in a single step by affinity chromatography on mucin coupled Sepharose 4B column, determined by its fine sugar specificity by glycan array analysis and studied for its clinical potential in cancer and HIV research. 28472687 7 31 theme cell 1149:1152 arg1 HT 1160:1161 HT 29 1160:1164 HT 29 1160:1164 DBL showed dose and time dependent growth inhibitory effects on all the three cell lines HT 29, SW 620 and HepG2 with IC50 of 110μg, 9.8μg, 40μg respectively at 72h. 28472687 7 31 theme cell 1149:1152 arg1 SW 1167:1168 SW 620 1167:1172 SW 620 1167:1172 DBL showed dose and time dependent growth inhibitory effects on all the three cell lines HT 29, SW 620 and HepG2 with IC50 of 110μg, 9.8μg, 40μg respectively at 72h. 28472687 7 31 theme cell 1149:1152 arg1 HepG2 1178:1182 HepG2 1178:1182 HepG2 1178:1182 DBL showed dose and time dependent growth inhibitory effects on all the three cell lines HT 29, SW 620 and HepG2 with IC50 of 110μg, 9.8μg, 40μg respectively at 72h. 28472687 7 31 theme cell 1149:1152 arg1 lines 1154:1158 the three cell lines 1139:1158 all the three cell lines HT 29, SW 620 and HepG2 1135:1182 DBL showed dose and time dependent growth inhibitory effects on all the three cell lines HT 29, SW 620 and HepG2 with IC50 of 110μg, 9.8μg, 40μg respectively at 72h. 28472687 6 32 theme HepG2 1053:1057 arg1 lines 1064:1068 hepatocellular HepG2 cell lines 1038:1068 hepatocellular HepG2 cell lines 1038:1068 DBL showed strong binding to non-metastatic human colon epithelial cancer HT 29, metastatic SW 620 and hepatocellular HepG2 cell lines. 28472687 5 33 link N-linked 831:838 arg1 glycans 840:846 N-linked glycans 831:846 N-linked glycans of HIV envelope glycoprotein gp120 831:881 Glycan array analysis of DBL revealed its affinity toward high mannose N-linked glycans with enhanced affinity for terminal mannose including N-linked glycans of HIV envelope glycoprotein gp120 and has strong anti-reverse transcriptase activity. 28472687 3 34 theme 24kDa 530:534 arg1 lectin 504:509 lectin 504:509 lectin 504:509 SDS-PAGE showed that lectin is a monomer of Mr 24kDa. 28472687 3 34 theme 24kDa 530:534 arg1 monomer 516:522 a monomer 514:522 a monomer of Mr 24kDa 514:534 SDS-PAGE showed that lectin is a monomer of Mr 24kDa. 28472687 3 34 theme 24kDa 530:534 arg1 24kDa 530:534 Mr 24kDa 527:534 Mr 24kDa 527:534 SDS-PAGE showed that lectin is a monomer of Mr 24kDa. 28472687 2 35 dep D. 242:243 arg1 bulbifera 245:253 D. bulbifera 242:253 D. bulbifera 242:253 A mannose binding lectin from bulbils of D. bulbifera was purified in a single step by affinity chromatography on mucin coupled Sepharose 4B column, determined by its fine sugar specificity by glycan array analysis and studied for its clinical potential in cancer and HIV research. 28472687 7 36 dep dependent 1096:1104 arg1 dose 1082:1085 dose 1082:1085 dose 1082:1085 DBL showed dose and time dependent growth inhibitory effects on all the three cell lines HT 29, SW 620 and HepG2 with IC50 of 110μg, 9.8μg, 40μg respectively at 72h. 28472687 6 37 theme cell 1059:1062 arg1 lines 1064:1068 hepatocellular HepG2 cell lines 1038:1068 hepatocellular HepG2 cell lines 1038:1068 DBL showed strong binding to non-metastatic human colon epithelial cancer HT 29, metastatic SW 620 and hepatocellular HepG2 cell lines. 28472687 8 38 theme Inhibitory 1237:1246 arg1 effect 1248:1253 Inhibitory effect 1237:1253 Inhibitory effect of DBL 1237:1260 Inhibitory effect of DBL was effectively blocked in presence of competing glycans like mucin. 28472687 5 39 theme high 747:750 arg1 glycans 769:775 high mannose N-linked glycans 747:775 high mannose N-linked glycans 747:775 Glycan array analysis of DBL revealed its affinity toward high mannose N-linked glycans with enhanced affinity for terminal mannose including N-linked glycans of HIV envelope glycoprotein gp120 and has strong anti-reverse transcriptase activity. 28472687 2 40 from bulbils 231:237 arg1 lectin 219:224 A mannose binding lectin 201:224 A mannose binding lectin from bulbils of D. bulbifera 201:253 A mannose binding lectin from bulbils of D. bulbifera was purified in a single step by affinity chromatography on mucin coupled Sepharose 4B column, determined by its fine sugar specificity by glycan array analysis and studied for its clinical potential in cancer and HIV research. 28472687 2 41 theme glycan 394:399 arg1 analysis 407:414 glycan array analysis 394:414 glycan array analysis 394:414 A mannose binding lectin from bulbils of D. bulbifera was purified in a single step by affinity chromatography on mucin coupled Sepharose 4B column, determined by its fine sugar specificity by glycan array analysis and studied for its clinical potential in cancer and HIV research. 28472687 2 42 theme array 401:405 arg1 analysis 407:414 glycan array analysis 394:414 glycan array analysis 394:414 A mannose binding lectin from bulbils of D. bulbifera was purified in a single step by affinity chromatography on mucin coupled Sepharose 4B column, determined by its fine sugar specificity by glycan array analysis and studied for its clinical potential in cancer and HIV research. 28472687 6 43 theme strong 946:951 arg1 binding 953:959 strong binding 946:959 strong binding to non-metastatic human colon epithelial cancer HT 29, metastatic SW 620 and hepatocellular HepG2 cell lines 946:1068 DBL showed strong binding to non-metastatic human colon epithelial cancer HT 29, metastatic SW 620 and hepatocellular HepG2 cell lines. 28472687 9 44 theme clinical 1349:1356 arg1 potential 1358:1366 promising clinical potential 1339:1366 promising clinical potential 1339:1366 DBL has promising clinical potential both in cancer and HIV research. 28472687 1 45 theme Dioscorea 119:127 arg1 remedy 177:182 a folk remedy 170:182 a folk remedy 170:182 Dioscorea bulbifera or air potato has been used as a folk remedy to treat cancer. 28472687 1 45 theme Dioscorea 119:127 arg1 bulbifera 129:137 Dioscorea bulbifera 119:137 Dioscorea bulbifera 119:137 Dioscorea bulbifera or air potato has been used as a folk remedy to treat cancer. 28472687 1 45 theme Dioscorea 119:127 arg1 potato 146:151 air potato 142:151 air potato 142:151 Dioscorea bulbifera or air potato has been used as a folk remedy to treat cancer. 28472687 7 46 theme 110μg 1197:1201 arg1 IC50 1189:1192 IC50 1189:1192 IC50 of 110μg 1189:1201 DBL showed dose and time dependent growth inhibitory effects on all the three cell lines HT 29, SW 620 and HepG2 with IC50 of 110μg, 9.8μg, 40μg respectively at 72h. 28472687 8 47 theme DBL 1258:1260 arg1 effect 1248:1253 Inhibitory effect 1237:1253 Inhibitory effect of DBL 1237:1260 Inhibitory effect of DBL was effectively blocked in presence of competing glycans like mucin. 28472687 9 48 dep research 1391:1398 arg1 both 1368:1371 both 1368:1371 both 1368:1371 DBL has promising clinical potential both in cancer and HIV research. 28472687 6 49 theme SW 1027:1028 arg1 620 1030:1032 metastatic SW 620 1016:1032 metastatic SW 620 1016:1032 DBL showed strong binding to non-metastatic human colon epithelial cancer HT 29, metastatic SW 620 and hepatocellular HepG2 cell lines. 28472687 6 50 theme hepatocellular 1038:1051 arg1 lines 1064:1068 hepatocellular HepG2 cell lines 1038:1068 hepatocellular HepG2 cell lines 1038:1068 DBL showed strong binding to non-metastatic human colon epithelial cancer HT 29, metastatic SW 620 and hepatocellular HepG2 cell lines. 28472687 5 51 theme terminal 804:811 arg1 mannose 813:819 terminal mannose 804:819 terminal mannose 804:819 Glycan array analysis of DBL revealed its affinity toward high mannose N-linked glycans with enhanced affinity for terminal mannose including N-linked glycans of HIV envelope glycoprotein gp120 and has strong anti-reverse transcriptase activity. 28472687 0 52 theme biological 35:44 arg1 significance 46:57 biological significance 35:57 biological significance 35:57 Purification, characterization and biological significance of mannose binding lectin from Dioscorea bulbifera bulbils. 28472687 2 53 theme clinical 436:443 arg1 potential 445:453 its clinical potential 432:453 its clinical potential 432:453 A mannose binding lectin from bulbils of D. bulbifera was purified in a single step by affinity chromatography on mucin coupled Sepharose 4B column, determined by its fine sugar specificity by glycan array analysis and studied for its clinical potential in cancer and HIV research. 28472687 2 54 theme sugar 373:377 arg1 specificity 379:389 its fine sugar specificity 364:389 its fine sugar specificity 364:389 A mannose binding lectin from bulbils of D. bulbifera was purified in a single step by affinity chromatography on mucin coupled Sepharose 4B column, determined by its fine sugar specificity by glycan array analysis and studied for its clinical potential in cancer and HIV research. 28472687 0 55 theme mannose 62:68 arg1 lectin 78:83 mannose binding lectin 62:83 mannose binding lectin 62:83 Purification, characterization and biological significance of mannose binding lectin from Dioscorea bulbifera bulbils. 28472687 9 56 theme cancer 1376:1381 arg1 research 1391:1398 cancer and HIV research 1376:1398 cancer and HIV research 1376:1398 DBL has promising clinical potential both in cancer and HIV research. 28472687 8 57 theme competing 1301:1309 arg1 glycans 1311:1317 competing glycans 1301:1317 competing glycans like mucin 1301:1328 Inhibitory effect of DBL was effectively blocked in presence of competing glycans like mucin. 28472687 5 58 theme DBL 714:716 arg1 analysis 702:709 Glycan array analysis 689:709 Glycan array analysis of DBL 689:716 Glycan array analysis of DBL revealed its affinity toward high mannose N-linked glycans with enhanced affinity for terminal mannose including N-linked glycans of HIV envelope glycoprotein gp120 and has strong anti-reverse transcriptase activity. 28472687 2 59 theme binding 211:217 arg1 lectin 219:224 A mannose binding lectin 201:224 A mannose binding lectin from bulbils of D. bulbifera 201:253 A mannose binding lectin from bulbils of D. bulbifera was purified in a single step by affinity chromatography on mucin coupled Sepharose 4B column, determined by its fine sugar specificity by glycan array analysis and studied for its clinical potential in cancer and HIV research. 28472687 2 60 theme coupled 321:327 arg1 column 342:347 mucin coupled Sepharose 4B column 315:347 mucin coupled Sepharose 4B column 315:347 A mannose binding lectin from bulbils of D. bulbifera was purified in a single step by affinity chromatography on mucin coupled Sepharose 4B column, determined by its fine sugar specificity by glycan array analysis and studied for its clinical potential in cancer and HIV research. 28472687 5 61 theme mannose 752:758 arg1 glycans 769:775 high mannose N-linked glycans 747:775 high mannose N-linked glycans 747:775 Glycan array analysis of DBL revealed its affinity toward high mannose N-linked glycans with enhanced affinity for terminal mannose including N-linked glycans of HIV envelope glycoprotein gp120 and has strong anti-reverse transcriptase activity. 28472687 2 62 theme mannose 203:209 arg1 lectin 219:224 A mannose binding lectin 201:224 A mannose binding lectin from bulbils of D. bulbifera 201:253 A mannose binding lectin from bulbils of D. bulbifera was purified in a single step by affinity chromatography on mucin coupled Sepharose 4B column, determined by its fine sugar specificity by glycan array analysis and studied for its clinical potential in cancer and HIV research. 28472687 5 63 contain has 887:889 arg1 analysis 702:709 Glycan array analysis 689:709 Glycan array analysis of DBL 689:716 Glycan array analysis of DBL revealed its affinity toward high mannose N-linked glycans with enhanced affinity for terminal mannose including N-linked glycans of HIV envelope glycoprotein gp120 and has strong anti-reverse transcriptase activity. 28472687 5 63 contain has 887:889 arg2 activity 925:932 strong anti-reverse transcriptase activity 891:932 strong anti-reverse transcriptase activity 891:932 Glycan array analysis of DBL revealed its affinity toward high mannose N-linked glycans with enhanced affinity for terminal mannose including N-linked glycans of HIV envelope glycoprotein gp120 and has strong anti-reverse transcriptase activity. 28472687 2 64 theme mucin 315:319 arg1 column 342:347 mucin coupled Sepharose 4B column 315:347 mucin coupled Sepharose 4B column 315:347 A mannose binding lectin from bulbils of D. bulbifera was purified in a single step by affinity chromatography on mucin coupled Sepharose 4B column, determined by its fine sugar specificity by glycan array analysis and studied for its clinical potential in cancer and HIV research. 28472687 3 65 theme Mr 527:528 arg1 24kDa 530:534 Mr 24kDa 527:534 Mr 24kDa 527:534 SDS-PAGE showed that lectin is a monomer of Mr 24kDa. 28472687 7 66 dep lines 1154:1158 arg1 HT 1160:1161 HT 29 1160:1164 HT 29 1160:1164 DBL showed dose and time dependent growth inhibitory effects on all the three cell lines HT 29, SW 620 and HepG2 with IC50 of 110μg, 9.8μg, 40μg respectively at 72h. 28472687 7 66 dep lines 1154:1158 arg1 SW 1167:1168 SW 620 1167:1172 SW 620 1167:1172 DBL showed dose and time dependent growth inhibitory effects on all the three cell lines HT 29, SW 620 and HepG2 with IC50 of 110μg, 9.8μg, 40μg respectively at 72h. 28472687 7 66 dep lines 1154:1158 arg1 HepG2 1178:1182 HepG2 1178:1182 HepG2 1178:1182 DBL showed dose and time dependent growth inhibitory effects on all the three cell lines HT 29, SW 620 and HepG2 with IC50 of 110μg, 9.8μg, 40μg respectively at 72h. 28472687 7 66 dep lines 1154:1158 arg1 lines 1154:1158 the three cell lines 1139:1158 all the three cell lines HT 29, SW 620 and HepG2 1135:1182 DBL showed dose and time dependent growth inhibitory effects on all the three cell lines HT 29, SW 620 and HepG2 with IC50 of 110μg, 9.8μg, 40μg respectively at 72h. 28472687 1 67 theme air 142:144 arg1 remedy 177:182 a folk remedy 170:182 a folk remedy 170:182 Dioscorea bulbifera or air potato has been used as a folk remedy to treat cancer. 28472687 1 67 theme air 142:144 arg1 bulbifera 129:137 Dioscorea bulbifera 119:137 Dioscorea bulbifera 119:137 Dioscorea bulbifera or air potato has been used as a folk remedy to treat cancer. 28472687 1 67 theme air 142:144 arg1 potato 146:151 air potato 142:151 air potato 142:151 Dioscorea bulbifera or air potato has been used as a folk remedy to treat cancer. 28472687 9 68 theme HIV 1387:1389 arg1 research 1391:1398 cancer and HIV research 1376:1398 cancer and HIV research 1376:1398 DBL has promising clinical potential both in cancer and HIV research. 28472687 5 69 gly glycoprotein 864:875 arg1 glycoprotein 864:875 HIV envelope glycoprotein gp120 851:881 HIV envelope glycoprotein gp120 851:881 Glycan array analysis of DBL revealed its affinity toward high mannose N-linked glycans with enhanced affinity for terminal mannose including N-linked glycans of HIV envelope glycoprotein gp120 and has strong anti-reverse transcriptase activity. 28472687 0 70 from bulbils 110:116 arg1 characterization 14:29 characterization 14:29 characterization 14:29 Purification, characterization and biological significance of mannose binding lectin from Dioscorea bulbifera bulbils. 28472687 0 70 from bulbils 110:116 arg1 significance 46:57 biological significance 35:57 biological significance 35:57 Purification, characterization and biological significance of mannose binding lectin from Dioscorea bulbifera bulbils. 28472687 0 70 from bulbils 110:116 arg1 Purification 0:11 Purification 0:11 Purification 0:11 Purification, characterization and biological significance of mannose binding lectin from Dioscorea bulbifera bulbils. 28472687 2 71 theme D. 242:243 arg1 bulbils 231:237 bulbils 231:237 bulbils of D. bulbifera 231:253 A mannose binding lectin from bulbils of D. bulbifera was purified in a single step by affinity chromatography on mucin coupled Sepharose 4B column, determined by its fine sugar specificity by glycan array analysis and studied for its clinical potential in cancer and HIV research. 28472687 5 72 theme anti-reverse 898:909 arg1 transcriptase 911:923 strong anti-reverse transcriptase 891:923 strong anti-reverse transcriptase activity 891:932 Glycan array analysis of DBL revealed its affinity toward high mannose N-linked glycans with enhanced affinity for terminal mannose including N-linked glycans of HIV envelope glycoprotein gp120 and has strong anti-reverse transcriptase activity. 28472687 4 73 theme rabbit 559:564 arg1 erythrocytes 566:577 rabbit erythrocytes 559:577 rabbit erythrocytes 559:577 DBL agglutinated only rabbit erythrocytes and was inhibited by mucin, asialomucin, fetuin, asialofetuin and transferrin but not by any monosaccharides. 28472687 2 74 theme HIV 469:471 arg1 research 473:480 cancer and HIV research 458:480 research 473:480 A mannose binding lectin from bulbils of D. bulbifera was purified in a single step by affinity chromatography on mucin coupled Sepharose 4B column, determined by its fine sugar specificity by glycan array analysis and studied for its clinical potential in cancer and HIV research. 28472687 6 75 theme metastatic 1016:1025 arg1 620 1030:1032 metastatic SW 620 1016:1032 metastatic SW 620 1016:1032 DBL showed strong binding to non-metastatic human colon epithelial cancer HT 29, metastatic SW 620 and hepatocellular HepG2 cell lines. 28472687 5 76 link N-linked 760:767 arg1 glycans 769:775 high mannose N-linked glycans 747:775 high mannose N-linked glycans 747:775 Glycan array analysis of DBL revealed its affinity toward high mannose N-linked glycans with enhanced affinity for terminal mannose including N-linked glycans of HIV envelope glycoprotein gp120 and has strong anti-reverse transcriptase activity. 28472687 5 77 theme HIV 851:853 arg1 gp120 877:881 HIV envelope glycoprotein gp120 851:881 HIV envelope glycoprotein gp120 851:881 Glycan array analysis of DBL revealed its affinity toward high mannose N-linked glycans with enhanced affinity for terminal mannose including N-linked glycans of HIV envelope glycoprotein gp120 and has strong anti-reverse transcriptase activity. 28472687 5 78 theme N-linked 831:838 arg1 glycans 840:846 N-linked glycans 831:846 N-linked glycans of HIV envelope glycoprotein gp120 831:881 Glycan array analysis of DBL revealed its affinity toward high mannose N-linked glycans with enhanced affinity for terminal mannose including N-linked glycans of HIV envelope glycoprotein gp120 and has strong anti-reverse transcriptase activity. 28472687 6 79 theme HT 1009:1010 arg1 cancer 1002:1007 non-metastatic human colon epithelial cancer HT 29 964:1013 non-metastatic human colon epithelial cancer HT 29 964:1013 DBL showed strong binding to non-metastatic human colon epithelial cancer HT 29, metastatic SW 620 and hepatocellular HepG2 cell lines. 28472687 0 80 theme binding 70:76 arg1 lectin 78:83 mannose binding lectin 62:83 mannose binding lectin 62:83 Purification, characterization and biological significance of mannose binding lectin from Dioscorea bulbifera bulbils. 28472687 5 81 theme enhanced 782:789 arg1 affinity 791:798 enhanced affinity 782:798 enhanced affinity for terminal mannose including N-linked glycans of HIV envelope glycoprotein gp120 782:881 Glycan array analysis of DBL revealed its affinity toward high mannose N-linked glycans with enhanced affinity for terminal mannose including N-linked glycans of HIV envelope glycoprotein gp120 and has strong anti-reverse transcriptase activity. 28472687 5 82 theme envelope 855:862 arg1 gp120 877:881 HIV envelope glycoprotein gp120 851:881 HIV envelope glycoprotein gp120 851:881 Glycan array analysis of DBL revealed its affinity toward high mannose N-linked glycans with enhanced affinity for terminal mannose including N-linked glycans of HIV envelope glycoprotein gp120 and has strong anti-reverse transcriptase activity. 28472687 5 83 theme Glycan 689:694 arg1 analysis 702:709 Glycan array analysis 689:709 Glycan array analysis of DBL 689:716 Glycan array analysis of DBL revealed its affinity toward high mannose N-linked glycans with enhanced affinity for terminal mannose including N-linked glycans of HIV envelope glycoprotein gp120 and has strong anti-reverse transcriptase activity. 24190977 4 0 theme cell 671:674 arg1 lines 676:680 patient-derived diffuse large B-cell lymphoma cell lines 625:680 patient-derived diffuse large B-cell lymphoma cell lines 625:680 From patient-derived diffuse large B-cell lymphoma cell lines, we mapped 2383 glycosites on 1321 protein groups, which were highly enriched for cell membrane proteins. 24190977 10 1 theme cancer 1624:1629 arg1 types 1631:1635 cancer types 1624:1635 cancer types 1624:1635 Thus, enrichment of a class of post-translationally modified peptides can classify cancer types as well as reveal cancer specific mechanistic changes. 24190977 7 2 theme PMID 1182:1185 arg1 22442255 1187:1194 MCP 2012 PMID 22442255 1173:1194 MCP 2012 PMID 22442255 1173:1194 MCP 2012 PMID 22442255). 24190977 2 3 theme modifications 408:420 arg1 quantification 352:365 the global quantification 341:365 the global quantification of proteins and their post-translational modifications 341:420 Technological advances in mass spectrometry-based proteomics promise to complete the picture by allowing the global quantification of proteins and their post-translational modifications. 24190977 4 4 link patient-derived 625:639 arg1 lines 676:680 patient-derived diffuse large B-cell lymphoma cell lines 625:680 patient-derived diffuse large B-cell lymphoma cell lines 625:680 From patient-derived diffuse large B-cell lymphoma cell lines, we mapped 2383 glycosites on 1321 protein groups, which were highly enriched for cell membrane proteins. 24190977 10 5 theme cancer 1655:1660 arg1 changes 1683:1689 cancer specific mechanistic changes 1655:1689 cancer specific mechanistic changes 1655:1689 Thus, enrichment of a class of post-translationally modified peptides can classify cancer types as well as reveal cancer specific mechanistic changes. 24190977 7 6 theme MCP 1173:1175 arg1 22442255 1187:1194 MCP 2012 PMID 22442255 1173:1194 MCP 2012 PMID 22442255 1173:1194 MCP 2012 PMID 22442255). 24190977 3 7 from glycoproteins 587:599 arg1 cells 613:617 lymphoma cells 604:617 lymphoma cells 604:617 Here we use N-glyco FASP, a recently developed mass spectrometric approach using lectin-enrichment, in conjunction with a super-SILAC approach to quantify N-linked glycoproteins in lymphoma cells. 24190977 9 8 theme known 1510:1514 arg1 ones 1535:1538 known NF-kappa-B related ones 1510:1538 known NF-kappa-B related ones 1510:1538 Detailed examination of glycosites and glycoprotein expression levels uncovered, among other interesting findings, enrichment of transcription factor binding motifs, including known NF-kappa-B related ones. 24190977 8 9 theme high 1219:1222 arg1 correlation 1224:1234 the high correlation 1215:1234 the high correlation that we observed between the expression level of the glycosites and their corresponding proteins 1215:1331 This conforms to the high correlation that we observed between the expression level of the glycosites and their corresponding proteins. 24190977 0 10 link N-linked 0:7 arg1 glycosylation 9:21 N-linked glycosylation 0:21 N-linked glycosylation 0:21 N-linked glycosylation enrichment for in-depth cell surface proteomics of diffuse large B-cell lymphoma subtypes. 24190977 0 11 theme N-linked 0:7 arg1 glycosylation 9:21 N-linked glycosylation 0:21 N-linked glycosylation 0:21 N-linked glycosylation enrichment for in-depth cell surface proteomics of diffuse large B-cell lymphoma subtypes. 24190977 5 12 theme expression 928:937 arg1 studies 939:945 gene expression studies 923:945 gene expression studies 923:945 This N-glyco subproteome alone allowed the segregation of the ABC from the GCB subtypes of diffuse large B-cell lymphoma, which before gene expression studies had been considered one disease entity. 24190977 9 13 theme NF-kappa-B 1516:1525 arg1 ones 1535:1538 known NF-kappa-B related ones 1510:1538 known NF-kappa-B related ones 1510:1538 Detailed examination of glycosites and glycoprotein expression levels uncovered, among other interesting findings, enrichment of transcription factor binding motifs, including known NF-kappa-B related ones. 24190977 8 14 theme corresponding 1310:1322 arg1 proteins 1324:1331 their corresponding proteins 1304:1331 their corresponding proteins 1304:1331 This conforms to the high correlation that we observed between the expression level of the glycosites and their corresponding proteins. 24190977 10 15 theme mechanistic 1671:1681 arg1 changes 1683:1689 cancer specific mechanistic changes 1655:1689 cancer specific mechanistic changes 1655:1689 Thus, enrichment of a class of post-translationally modified peptides can classify cancer types as well as reveal cancer specific mechanistic changes. 24190977 3 16 theme N-linked 578:585 arg1 glycoproteins 587:599 N-linked glycoproteins 578:599 N-linked glycoproteins in lymphoma cells 578:617 Here we use N-glyco FASP, a recently developed mass spectrometric approach using lectin-enrichment, in conjunction with a super-SILAC approach to quantify N-linked glycoproteins in lymphoma cells. 24190977 1 17 theme biology 227:233 arg1 understanding 204:216 our understanding 200:216 our understanding of their biology 200:233 Global analysis of lymphoma genome integrity and transcriptomes tremendously advanced our understanding of their biology. 24190977 5 18 theme N-glyco 793:799 arg1 subproteome 801:811 This N-glyco subproteome 788:811 This N-glyco subproteome 788:811 This N-glyco subproteome alone allowed the segregation of the ABC from the GCB subtypes of diffuse large B-cell lymphoma, which before gene expression studies had been considered one disease entity. 24190977 8 19 gly glycosites 1289:1298 arg2 glycosites 1289:1298 the glycosites 1285:1298 the glycosites 1285:1298 This conforms to the high correlation that we observed between the expression level of the glycosites and their corresponding proteins. 24190977 2 20 theme mass 262:265 arg1 proteomics 286:295 mass spectrometry-based proteomics 262:295 mass spectrometry-based proteomics 262:295 Technological advances in mass spectrometry-based proteomics promise to complete the picture by allowing the global quantification of proteins and their post-translational modifications. 24190977 9 21 gly glycosites 1358:1367 arg2 glycosites 1358:1367 glycosites 1358:1367 glycosites 1358:1367 Detailed examination of glycosites and glycoprotein expression levels uncovered, among other interesting findings, enrichment of transcription factor binding motifs, including known NF-kappa-B related ones. 24190977 1 22 theme genome 142:147 arg1 integrity 149:157 lymphoma genome integrity 133:157 lymphoma genome integrity 133:157 Global analysis of lymphoma genome integrity and transcriptomes tremendously advanced our understanding of their biology. 24190977 9 23 gly glycoprotein 1373:1384 arg1 glycoprotein 1373:1384 glycoprotein expression levels 1373:1402 glycoprotein expression levels 1373:1402 Detailed examination of glycosites and glycoprotein expression levels uncovered, among other interesting findings, enrichment of transcription factor binding motifs, including known NF-kappa-B related ones. 24190977 9 24 theme Detailed 1334:1341 arg1 examination 1343:1353 Detailed examination 1334:1353 Detailed examination of glycosites and glycoprotein expression levels 1334:1402 Detailed examination of glycosites and glycoprotein expression levels uncovered, among other interesting findings, enrichment of transcription factor binding motifs, including known NF-kappa-B related ones. 24190977 6 25 from segregators 1099:1109 arg1 study 1130:1134 a deep proteome study 1114:1134 a deep proteome study of these subtypes 1114:1152 Encouragingly, many of the glycopeptides driving the segregation belong to proteins previously characterized as segregators in a deep proteome study of these subtypes (S. J. Deeb et al. 24190977 4 26 theme membrane 769:776 arg1 proteins 778:785 cell membrane proteins 764:785 cell membrane proteins 764:785 From patient-derived diffuse large B-cell lymphoma cell lines, we mapped 2383 glycosites on 1321 protein groups, which were highly enriched for cell membrane proteins. 24190977 0 27 theme large 82:86 arg1 lymphoma 95:102 diffuse large B-cell lymphoma 74:102 diffuse large B-cell lymphoma subtypes 74:111 N-linked glycosylation enrichment for in-depth cell surface proteomics of diffuse large B-cell lymphoma subtypes. 24190977 5 28 theme disease 971:977 arg1 entity 979:984 one disease entity 967:984 one disease entity 967:984 This N-glyco subproteome alone allowed the segregation of the ABC from the GCB subtypes of diffuse large B-cell lymphoma, which before gene expression studies had been considered one disease entity. 24190977 0 29 theme lymphoma 95:102 arg1 subtypes 104:111 diffuse large B-cell lymphoma subtypes 74:111 diffuse large B-cell lymphoma subtypes 74:111 N-linked glycosylation enrichment for in-depth cell surface proteomics of diffuse large B-cell lymphoma subtypes. 24190977 9 30 theme expression 1386:1395 arg1 levels 1397:1402 glycoprotein expression levels 1373:1402 glycoprotein expression levels 1373:1402 Detailed examination of glycosites and glycoprotein expression levels uncovered, among other interesting findings, enrichment of transcription factor binding motifs, including known NF-kappa-B related ones. 24190977 3 31 dep developed 460:468 arg1 spectrometric 475:487 spectrometric 475:487 spectrometric 475:487 Here we use N-glyco FASP, a recently developed mass spectrometric approach using lectin-enrichment, in conjunction with a super-SILAC approach to quantify N-linked glycoproteins in lymphoma cells. 24190977 0 32 theme diffuse 74:80 arg1 lymphoma 95:102 diffuse large B-cell lymphoma 74:102 diffuse large B-cell lymphoma subtypes 74:111 N-linked glycosylation enrichment for in-depth cell surface proteomics of diffuse large B-cell lymphoma subtypes. 24190977 5 33 theme diffuse 879:885 arg1 lymphoma 900:907 diffuse large B-cell lymphoma 879:907 diffuse large B-cell lymphoma 879:907 This N-glyco subproteome alone allowed the segregation of the ABC from the GCB subtypes of diffuse large B-cell lymphoma, which before gene expression studies had been considered one disease entity. 24190977 4 34 theme patient-derived 625:639 arg1 lines 676:680 patient-derived diffuse large B-cell lymphoma cell lines 625:680 patient-derived diffuse large B-cell lymphoma cell lines 625:680 From patient-derived diffuse large B-cell lymphoma cell lines, we mapped 2383 glycosites on 1321 protein groups, which were highly enriched for cell membrane proteins. 24190977 5 35 theme B-cell 893:898 arg1 lymphoma 900:907 diffuse large B-cell lymphoma 879:907 diffuse large B-cell lymphoma 879:907 This N-glyco subproteome alone allowed the segregation of the ABC from the GCB subtypes of diffuse large B-cell lymphoma, which before gene expression studies had been considered one disease entity. 24190977 1 36 theme Global 114:119 arg1 analysis 121:128 Global analysis 114:128 Global analysis of lymphoma genome integrity and transcriptomes 114:176 Global analysis of lymphoma genome integrity and transcriptomes tremendously advanced our understanding of their biology. 24190977 3 37 theme developed 460:468 arg1 FASP 443:446 N-glyco FASP 435:446 N-glyco FASP 435:446 Here we use N-glyco FASP, a recently developed mass spectrometric approach using lectin-enrichment, in conjunction with a super-SILAC approach to quantify N-linked glycoproteins in lymphoma cells. 24190977 3 37 theme developed 460:468 arg1 approach 489:496 a recently developed mass spectrometric approach 449:496 a recently developed mass spectrometric approach using lectin-enrichment 449:520 Here we use N-glyco FASP, a recently developed mass spectrometric approach using lectin-enrichment, in conjunction with a super-SILAC approach to quantify N-linked glycoproteins in lymphoma cells. 24190977 4 38 theme large 649:653 arg1 lymphoma 662:669 diffuse large B-cell lymphoma 641:669 patient-derived diffuse large B-cell lymphoma cell lines 625:680 From patient-derived diffuse large B-cell lymphoma cell lines, we mapped 2383 glycosites on 1321 protein groups, which were highly enriched for cell membrane proteins. 24190977 10 39 theme class 1563:1567 arg1 enrichment 1547:1556 enrichment 1547:1556 enrichment of a class of post-translationally modified peptides 1547:1609 Thus, enrichment of a class of post-translationally modified peptides can classify cancer types as well as reveal cancer specific mechanistic changes. 24190977 6 40 dep Deeb 1161:1164 arg1 al 1169:1170 S. J. Deeb et al 1155:1170 S. J. Deeb et al 1155:1170 Encouragingly, many of the glycopeptides driving the segregation belong to proteins previously characterized as segregators in a deep proteome study of these subtypes (S. J. Deeb et al. 24190977 0 41 theme in-depth 38:45 arg1 proteomics 60:69 in-depth cell surface proteomics 38:69 in-depth cell surface proteomics of diffuse large B-cell lymphoma subtypes 38:111 N-linked glycosylation enrichment for in-depth cell surface proteomics of diffuse large B-cell lymphoma subtypes. 24190977 9 42 theme interesting 1427:1437 arg1 findings 1439:1446 other interesting findings 1421:1446 other interesting findings 1421:1446 Detailed examination of glycosites and glycoprotein expression levels uncovered, among other interesting findings, enrichment of transcription factor binding motifs, including known NF-kappa-B related ones. 24190977 6 43 theme deep 1116:1119 arg1 study 1130:1134 a deep proteome study 1114:1134 a deep proteome study of these subtypes 1114:1152 Encouragingly, many of the glycopeptides driving the segregation belong to proteins previously characterized as segregators in a deep proteome study of these subtypes (S. J. Deeb et al. 24190977 2 44 theme post-translational 389:406 arg1 modifications 408:420 their post-translational modifications 383:420 their post-translational modifications 383:420 Technological advances in mass spectrometry-based proteomics promise to complete the picture by allowing the global quantification of proteins and their post-translational modifications. 24190977 0 45 theme surface 52:58 arg1 proteomics 60:69 in-depth cell surface proteomics 38:69 in-depth cell surface proteomics of diffuse large B-cell lymphoma subtypes 38:111 N-linked glycosylation enrichment for in-depth cell surface proteomics of diffuse large B-cell lymphoma subtypes. 24190977 10 46 theme peptides 1602:1609 arg1 class 1563:1567 a class 1561:1567 a class of post-translationally modified peptides 1561:1609 Thus, enrichment of a class of post-translationally modified peptides can classify cancer types as well as reveal cancer specific mechanistic changes. 24190977 0 47 dep enrichment 23:32 arg1 glycosylation 9:21 N-linked glycosylation 0:21 N-linked glycosylation 0:21 N-linked glycosylation enrichment for in-depth cell surface proteomics of diffuse large B-cell lymphoma subtypes. 24190977 9 48 theme related 1527:1533 arg1 ones 1535:1538 known NF-kappa-B related ones 1510:1538 known NF-kappa-B related ones 1510:1538 Detailed examination of glycosites and glycoprotein expression levels uncovered, among other interesting findings, enrichment of transcription factor binding motifs, including known NF-kappa-B related ones. 24190977 9 49 theme factor 1477:1482 arg1 ones 1535:1538 known NF-kappa-B related ones 1510:1538 known NF-kappa-B related ones 1510:1538 Detailed examination of glycosites and glycoprotein expression levels uncovered, among other interesting findings, enrichment of transcription factor binding motifs, including known NF-kappa-B related ones. 24190977 9 49 theme factor 1477:1482 arg1 motifs 1492:1497 transcription factor binding motifs 1463:1497 transcription factor binding motifs 1463:1497 Detailed examination of glycosites and glycoprotein expression levels uncovered, among other interesting findings, enrichment of transcription factor binding motifs, including known NF-kappa-B related ones. 24190977 7 50 theme 2012 1177:1180 arg1 22442255 1187:1194 MCP 2012 PMID 22442255 1173:1194 MCP 2012 PMID 22442255 1173:1194 MCP 2012 PMID 22442255). 24190977 9 51 theme motifs 1492:1497 arg1 enrichment 1449:1458 enrichment 1449:1458 enrichment of transcription factor binding motifs, including known NF-kappa-B related ones 1449:1538 Detailed examination of glycosites and glycoprotein expression levels uncovered, among other interesting findings, enrichment of transcription factor binding motifs, including known NF-kappa-B related ones. 24190977 4 52 theme lymphoma 662:669 arg1 lines 676:680 patient-derived diffuse large B-cell lymphoma cell lines 625:680 patient-derived diffuse large B-cell lymphoma cell lines 625:680 From patient-derived diffuse large B-cell lymphoma cell lines, we mapped 2383 glycosites on 1321 protein groups, which were highly enriched for cell membrane proteins. 24190977 10 53 theme specific 1662:1669 arg1 changes 1683:1689 cancer specific mechanistic changes 1655:1689 cancer specific mechanistic changes 1655:1689 Thus, enrichment of a class of post-translationally modified peptides can classify cancer types as well as reveal cancer specific mechanistic changes. 24190977 6 54 gly glycopeptides 1014:1026 arg2 glycopeptides 1014:1026 the glycopeptides 1010:1026 the glycopeptides driving the segregation 1010:1050 Encouragingly, many of the glycopeptides driving the segregation belong to proteins previously characterized as segregators in a deep proteome study of these subtypes (S. J. Deeb et al. 24190977 3 55 theme lymphoma 604:611 arg1 cells 613:617 lymphoma cells 604:617 lymphoma cells 604:617 Here we use N-glyco FASP, a recently developed mass spectrometric approach using lectin-enrichment, in conjunction with a super-SILAC approach to quantify N-linked glycoproteins in lymphoma cells. 24190977 5 56 theme gene 923:926 arg1 studies 939:945 gene expression studies 923:945 gene expression studies 923:945 This N-glyco subproteome alone allowed the segregation of the ABC from the GCB subtypes of diffuse large B-cell lymphoma, which before gene expression studies had been considered one disease entity. 24190977 5 57 theme ABC 850:852 arg1 segregation 831:841 the segregation 827:841 the segregation of the ABC from the GCB subtypes of diffuse large B-cell lymphoma, which before gene expression studies had been considered one disease entity 827:984 This N-glyco subproteome alone allowed the segregation of the ABC from the GCB subtypes of diffuse large B-cell lymphoma, which before gene expression studies had been considered one disease entity. 24190977 8 58 theme glycosites 1289:1298 arg1 level 1276:1280 the expression level 1261:1280 the expression level of the glycosites and their corresponding proteins 1261:1331 This conforms to the high correlation that we observed between the expression level of the glycosites and their corresponding proteins. 24190977 2 59 theme global 345:350 arg1 quantification 352:365 the global quantification 341:365 the global quantification of proteins and their post-translational modifications 341:420 Technological advances in mass spectrometry-based proteomics promise to complete the picture by allowing the global quantification of proteins and their post-translational modifications. 24190977 5 60 theme lymphoma 900:907 arg1 subtypes 867:874 the GCB subtypes 859:874 the GCB subtypes of diffuse large B-cell lymphoma, which before gene expression studies had been considered one disease entity 859:984 This N-glyco subproteome alone allowed the segregation of the ABC from the GCB subtypes of diffuse large B-cell lymphoma, which before gene expression studies had been considered one disease entity. 24190977 3 61 link N-linked 578:585 arg1 glycoproteins 587:599 N-linked glycoproteins 578:599 N-linked glycoproteins in lymphoma cells 578:617 Here we use N-glyco FASP, a recently developed mass spectrometric approach using lectin-enrichment, in conjunction with a super-SILAC approach to quantify N-linked glycoproteins in lymphoma cells. 24190977 3 62 with conjunction 526:536 arg1 approach 557:564 a super-SILAC approach 543:564 a super-SILAC approach to quantify N-linked glycoproteins in lymphoma cells 543:617 Here we use N-glyco FASP, a recently developed mass spectrometric approach using lectin-enrichment, in conjunction with a super-SILAC approach to quantify N-linked glycoproteins in lymphoma cells. 24190977 2 63 theme spectrometry-based 267:284 arg1 proteomics 286:295 mass spectrometry-based proteomics 262:295 mass spectrometry-based proteomics 262:295 Technological advances in mass spectrometry-based proteomics promise to complete the picture by allowing the global quantification of proteins and their post-translational modifications. 24190977 6 64 theme glycopeptides 1014:1026 arg1 many 1002:1005 many 1002:1005 many 1002:1005 Encouragingly, many of the glycopeptides driving the segregation belong to proteins previously characterized as segregators in a deep proteome study of these subtypes (S. J. Deeb et al. 24190977 6 64 theme glycopeptides 1014:1026 arg1 glycopeptides 1014:1026 the glycopeptides 1010:1026 the glycopeptides driving the segregation 1010:1050 Encouragingly, many of the glycopeptides driving the segregation belong to proteins previously characterized as segregators in a deep proteome study of these subtypes (S. J. Deeb et al. 24190977 4 65 theme protein 717:723 arg1 groups 725:730 1321 protein groups 712:730 1321 protein groups 712:730 From patient-derived diffuse large B-cell lymphoma cell lines, we mapped 2383 glycosites on 1321 protein groups, which were highly enriched for cell membrane proteins. 24190977 8 66 theme expression 1265:1274 arg1 level 1276:1280 the expression level 1261:1280 the expression level of the glycosites and their corresponding proteins 1261:1331 This conforms to the high correlation that we observed between the expression level of the glycosites and their corresponding proteins. 24190977 1 67 theme lymphoma 133:140 arg1 integrity 149:157 lymphoma genome integrity 133:157 lymphoma genome integrity 133:157 Global analysis of lymphoma genome integrity and transcriptomes tremendously advanced our understanding of their biology. 24190977 4 68 from glycosites 698:707 arg1 groups 725:730 1321 protein groups 712:730 1321 protein groups 712:730 From patient-derived diffuse large B-cell lymphoma cell lines, we mapped 2383 glycosites on 1321 protein groups, which were highly enriched for cell membrane proteins. 24190977 1 69 theme integrity 149:157 arg1 analysis 121:128 Global analysis 114:128 Global analysis of lymphoma genome integrity and transcriptomes 114:176 Global analysis of lymphoma genome integrity and transcriptomes tremendously advanced our understanding of their biology. 24190977 0 70 theme B-cell 88:93 arg1 lymphoma 95:102 diffuse large B-cell lymphoma 74:102 diffuse large B-cell lymphoma subtypes 74:111 N-linked glycosylation enrichment for in-depth cell surface proteomics of diffuse large B-cell lymphoma subtypes. 24190977 5 71 from subtypes 867:874 arg1 segregation 831:841 the segregation 827:841 the segregation of the ABC from the GCB subtypes of diffuse large B-cell lymphoma, which before gene expression studies had been considered one disease entity 827:984 This N-glyco subproteome alone allowed the segregation of the ABC from the GCB subtypes of diffuse large B-cell lymphoma, which before gene expression studies had been considered one disease entity. 24190977 1 72 theme transcriptomes 163:176 arg1 analysis 121:128 Global analysis 114:128 Global analysis of lymphoma genome integrity and transcriptomes 114:176 Global analysis of lymphoma genome integrity and transcriptomes tremendously advanced our understanding of their biology. 24190977 6 73 dep characterized 1082:1094 arg1 Deeb 1161:1164 Deeb 1161:1164 Deeb 1161:1164 Encouragingly, many of the glycopeptides driving the segregation belong to proteins previously characterized as segregators in a deep proteome study of these subtypes (S. J. Deeb et al. 24190977 6 73 dep characterized 1082:1094 arg1 proteins 1062:1069 proteins 1062:1069 proteins previously characterized as segregators in a deep proteome study of these subtypes (S. J. Deeb et al 1062:1170 Encouragingly, many of the glycopeptides driving the segregation belong to proteins previously characterized as segregators in a deep proteome study of these subtypes (S. J. Deeb et al. 24190977 4 74 theme cell 764:767 arg1 proteins 778:785 cell membrane proteins 764:785 cell membrane proteins 764:785 From patient-derived diffuse large B-cell lymphoma cell lines, we mapped 2383 glycosites on 1321 protein groups, which were highly enriched for cell membrane proteins. 24190977 0 75 theme subtypes 104:111 arg1 proteomics 60:69 in-depth cell surface proteomics 38:69 in-depth cell surface proteomics of diffuse large B-cell lymphoma subtypes 38:111 N-linked glycosylation enrichment for in-depth cell surface proteomics of diffuse large B-cell lymphoma subtypes. 24190977 9 76 theme glycosites 1358:1367 arg1 examination 1343:1353 Detailed examination 1334:1353 Detailed examination of glycosites and glycoprotein expression levels 1334:1402 Detailed examination of glycosites and glycoprotein expression levels uncovered, among other interesting findings, enrichment of transcription factor binding motifs, including known NF-kappa-B related ones. 24190977 3 77 gly glycoproteins 587:599 arg1 glycoproteins 587:599 N-linked glycoproteins 578:599 N-linked glycoproteins in lymphoma cells 578:617 Here we use N-glyco FASP, a recently developed mass spectrometric approach using lectin-enrichment, in conjunction with a super-SILAC approach to quantify N-linked glycoproteins in lymphoma cells. 24190977 3 78 theme super-SILAC 545:555 arg1 approach 557:564 a super-SILAC approach 543:564 a super-SILAC approach to quantify N-linked glycoproteins in lymphoma cells 543:617 Here we use N-glyco FASP, a recently developed mass spectrometric approach using lectin-enrichment, in conjunction with a super-SILAC approach to quantify N-linked glycoproteins in lymphoma cells. 24190977 9 79 theme glycoprotein 1373:1384 arg1 levels 1397:1402 glycoprotein expression levels 1373:1402 glycoprotein expression levels 1373:1402 Detailed examination of glycosites and glycoprotein expression levels uncovered, among other interesting findings, enrichment of transcription factor binding motifs, including known NF-kappa-B related ones. 24190977 4 80 gly glycosites 698:707 arg2 glycosites 698:707 2383 glycosites 693:707 2383 glycosites 693:707 From patient-derived diffuse large B-cell lymphoma cell lines, we mapped 2383 glycosites on 1321 protein groups, which were highly enriched for cell membrane proteins. 24190977 2 81 from advances 250:257 arg1 proteomics 286:295 mass spectrometry-based proteomics 262:295 mass spectrometry-based proteomics 262:295 Technological advances in mass spectrometry-based proteomics promise to complete the picture by allowing the global quantification of proteins and their post-translational modifications. 24190977 9 82 theme levels 1397:1402 arg1 examination 1343:1353 Detailed examination 1334:1353 Detailed examination of glycosites and glycoprotein expression levels 1334:1402 Detailed examination of glycosites and glycoprotein expression levels uncovered, among other interesting findings, enrichment of transcription factor binding motifs, including known NF-kappa-B related ones. 24190977 6 83 theme subtypes 1145:1152 arg1 study 1130:1134 a deep proteome study 1114:1134 a deep proteome study of these subtypes 1114:1152 Encouragingly, many of the glycopeptides driving the segregation belong to proteins previously characterized as segregators in a deep proteome study of these subtypes (S. J. Deeb et al. 24190977 4 84 theme diffuse 641:647 arg1 lymphoma 662:669 diffuse large B-cell lymphoma 641:669 patient-derived diffuse large B-cell lymphoma cell lines 625:680 From patient-derived diffuse large B-cell lymphoma cell lines, we mapped 2383 glycosites on 1321 protein groups, which were highly enriched for cell membrane proteins. 24190977 5 85 theme large 887:891 arg1 lymphoma 900:907 diffuse large B-cell lymphoma 879:907 diffuse large B-cell lymphoma 879:907 This N-glyco subproteome alone allowed the segregation of the ABC from the GCB subtypes of diffuse large B-cell lymphoma, which before gene expression studies had been considered one disease entity. 24190977 3 86 theme N-glyco 435:441 arg1 FASP 443:446 N-glyco FASP 435:446 N-glyco FASP 435:446 Here we use N-glyco FASP, a recently developed mass spectrometric approach using lectin-enrichment, in conjunction with a super-SILAC approach to quantify N-linked glycoproteins in lymphoma cells. 24190977 3 86 theme N-glyco 435:441 arg1 approach 489:496 a recently developed mass spectrometric approach 449:496 a recently developed mass spectrometric approach using lectin-enrichment 449:520 Here we use N-glyco FASP, a recently developed mass spectrometric approach using lectin-enrichment, in conjunction with a super-SILAC approach to quantify N-linked glycoproteins in lymphoma cells. 24190977 4 87 theme B-cell 655:660 arg1 lymphoma 662:669 diffuse large B-cell lymphoma 641:669 patient-derived diffuse large B-cell lymphoma cell lines 625:680 From patient-derived diffuse large B-cell lymphoma cell lines, we mapped 2383 glycosites on 1321 protein groups, which were highly enriched for cell membrane proteins. 24190977 0 88 theme cell 47:50 arg1 proteomics 60:69 in-depth cell surface proteomics 38:69 in-depth cell surface proteomics of diffuse large B-cell lymphoma subtypes 38:111 N-linked glycosylation enrichment for in-depth cell surface proteomics of diffuse large B-cell lymphoma subtypes. 24190977 9 89 theme other 1421:1425 arg1 findings 1439:1446 other interesting findings 1421:1446 other interesting findings 1421:1446 Detailed examination of glycosites and glycoprotein expression levels uncovered, among other interesting findings, enrichment of transcription factor binding motifs, including known NF-kappa-B related ones. 24190977 6 90 theme proteome 1121:1128 arg1 study 1130:1134 a deep proteome study 1114:1134 a deep proteome study of these subtypes 1114:1152 Encouragingly, many of the glycopeptides driving the segregation belong to proteins previously characterized as segregators in a deep proteome study of these subtypes (S. J. Deeb et al. 24190977 5 91 theme GCB 863:865 arg1 subtypes 867:874 the GCB subtypes 859:874 the GCB subtypes of diffuse large B-cell lymphoma, which before gene expression studies had been considered one disease entity 859:984 This N-glyco subproteome alone allowed the segregation of the ABC from the GCB subtypes of diffuse large B-cell lymphoma, which before gene expression studies had been considered one disease entity. 24190977 8 92 dep we 1241:1242 arg1 correlation 1224:1234 the high correlation 1215:1234 the high correlation that we observed between the expression level of the glycosites and their corresponding proteins 1215:1331 This conforms to the high correlation that we observed between the expression level of the glycosites and their corresponding proteins. 24190977 8 92 dep we 1241:1242 arg1 observed 1244:1251 observed 1244:1251 observed between the expression level of the glycosites and their corresponding proteins 1244:1331 This conforms to the high correlation that we observed between the expression level of the glycosites and their corresponding proteins. 24190977 2 93 theme Technological 236:248 arg1 advances 250:257 Technological advances 236:257 Technological advances in mass spectrometry-based proteomics 236:295 Technological advances in mass spectrometry-based proteomics promise to complete the picture by allowing the global quantification of proteins and their post-translational modifications. 24190977 10 94 theme modified 1593:1600 arg1 peptides 1602:1609 post-translationally modified peptides 1572:1609 post-translationally modified peptides 1572:1609 Thus, enrichment of a class of post-translationally modified peptides can classify cancer types as well as reveal cancer specific mechanistic changes. 24190977 2 95 theme proteins 370:377 arg1 quantification 352:365 the global quantification 341:365 the global quantification of proteins and their post-translational modifications 341:420 Technological advances in mass spectrometry-based proteomics promise to complete the picture by allowing the global quantification of proteins and their post-translational modifications. 24190977 9 96 theme transcription 1463:1475 arg1 ones 1535:1538 known NF-kappa-B related ones 1510:1538 known NF-kappa-B related ones 1510:1538 Detailed examination of glycosites and glycoprotein expression levels uncovered, among other interesting findings, enrichment of transcription factor binding motifs, including known NF-kappa-B related ones. 24190977 9 96 theme transcription 1463:1475 arg1 motifs 1492:1497 transcription factor binding motifs 1463:1497 transcription factor binding motifs 1463:1497 Detailed examination of glycosites and glycoprotein expression levels uncovered, among other interesting findings, enrichment of transcription factor binding motifs, including known NF-kappa-B related ones. 24190977 8 97 theme proteins 1324:1331 arg1 level 1276:1280 the expression level 1261:1280 the expression level of the glycosites and their corresponding proteins 1261:1331 This conforms to the high correlation that we observed between the expression level of the glycosites and their corresponding proteins. 24190977 9 98 theme binding 1484:1490 arg1 ones 1535:1538 known NF-kappa-B related ones 1510:1538 known NF-kappa-B related ones 1510:1538 Detailed examination of glycosites and glycoprotein expression levels uncovered, among other interesting findings, enrichment of transcription factor binding motifs, including known NF-kappa-B related ones. 24190977 9 98 theme binding 1484:1490 arg1 motifs 1492:1497 transcription factor binding motifs 1463:1497 transcription factor binding motifs 1463:1497 Detailed examination of glycosites and glycoprotein expression levels uncovered, among other interesting findings, enrichment of transcription factor binding motifs, including known NF-kappa-B related ones. 29284145 3 0 theme amino 433:437 arg1 acids 439:443 188 amino acids 429:443 188 amino acids 429:443 The full-length cDNA of bcIFNb gene consists of 806 nucleotides and the predicted bcIFNb protein contains 188 amino acids. 29284145 10 1 theme antiviral 1350:1358 arg1 ability 1360:1366 the similar antiviral ability 1338:1366 the similar antiviral ability 1338:1366 The un-glycosylated mutant bcIFNb-N92Q presented the similar antiviral ability as that of wild type bcIFNb, which demonstrated that N-linked glycosylation did not contribute directly to the antiviral property of this fish cytokine. 29284145 10 2 theme un-glycosylated 1293:1307 arg1 bcIFNb-N92Q 1316:1326 The un-glycosylated mutant bcIFNb-N92Q 1289:1326 The un-glycosylated mutant bcIFNb-N92Q 1289:1326 The un-glycosylated mutant bcIFNb-N92Q presented the similar antiviral ability as that of wild type bcIFNb, which demonstrated that N-linked glycosylation did not contribute directly to the antiviral property of this fish cytokine. 29284145 10 3 theme similar 1342:1348 arg1 ability 1360:1366 the similar antiviral ability 1338:1366 the similar antiviral ability 1338:1366 The un-glycosylated mutant bcIFNb-N92Q presented the similar antiviral ability as that of wild type bcIFNb, which demonstrated that N-linked glycosylation did not contribute directly to the antiviral property of this fish cytokine. 29284145 10 4 gly un-glycosylated 1293:1307 arg1 bcIFNb-N92Q 1316:1326 The un-glycosylated mutant bcIFNb-N92Q 1289:1326 The un-glycosylated mutant bcIFNb-N92Q 1289:1326 The un-glycosylated mutant bcIFNb-N92Q presented the similar antiviral ability as that of wild type bcIFNb, which demonstrated that N-linked glycosylation did not contribute directly to the antiviral property of this fish cytokine. 29284145 9 5 theme digestion 1146:1154 arg1 analysis 1156:1163 Glycosidase digestion analysis 1134:1163 Glycosidase digestion analysis 1134:1163 Glycosidase digestion analysis determined that bcIFNb was modified with N-linked glycosylation, which occurred on the Asn (N) of 92 site of this cytokine. 29284145 0 6 theme antiviral 78:86 arg1 IFNb 0:3 IFNb 0:3 IFNb of black carp 0:17 IFNb of black carp functions importantly in host innate immune response as an antiviral cytokine. 29284145 0 6 theme antiviral 78:86 arg1 cytokine 88:95 an antiviral cytokine 75:95 an antiviral cytokine 75:95 IFNb of black carp functions importantly in host innate immune response as an antiviral cytokine. 29284145 6 7 theme immunoblot 801:810 arg1 assay 812:816 immunoblot assay 801:816 immunoblot assay 801:816 bcIFNb was detected in both the whole cell lysate and the supernatant media of HEK293T cells or EPC cells transfected with bcIFNb through immunoblot assay. 29284145 5 8 theme bcIFNb 584:589 arg1 level 596:600 bcIFNb mRNA level 584:600 bcIFNb mRNA level 584:600 q-PCR analysis demonstrated that bcIFNb mRNA level varied in vivo and ex vivo in response to different stimuli. 29284145 2 9 from carp 258:261 arg1 interferon 227:236 one type I interferon 216:236 one type I interferon (bcIFNb) from black carp (Mylopharyngodon piceus) 216:286 In this study, one type I interferon (bcIFNb) from black carp (Mylopharyngodon piceus) has been cloned and characterized. 29284145 2 9 from carp 258:261 arg1 bcIFNb 239:244 bcIFNb 239:244 bcIFNb 239:244 In this study, one type I interferon (bcIFNb) from black carp (Mylopharyngodon piceus) has been cloned and characterized. 29284145 3 10 theme full-length 327:337 arg1 cDNA 339:342 The full-length cDNA 323:342 The full-length cDNA of bcIFNb gene 323:357 The full-length cDNA of bcIFNb gene consists of 806 nucleotides and the predicted bcIFNb protein contains 188 amino acids. 29284145 5 11 theme mRNA 591:594 arg1 level 596:600 bcIFNb mRNA level 584:600 bcIFNb mRNA level 584:600 q-PCR analysis demonstrated that bcIFNb mRNA level varied in vivo and ex vivo in response to different stimuli. 29284145 10 12 gly glycosylation 1430:1442 arg1 cytokine 1511:1518 this fish cytokine 1501:1518 this fish cytokine 1501:1518 The un-glycosylated mutant bcIFNb-N92Q presented the similar antiviral ability as that of wild type bcIFNb, which demonstrated that N-linked glycosylation did not contribute directly to the antiviral property of this fish cytokine. 29284145 5 13 theme different 644:652 arg1 stimuli 654:660 different stimuli 644:660 different stimuli 644:660 q-PCR analysis demonstrated that bcIFNb mRNA level varied in vivo and ex vivo in response to different stimuli. 29284145 9 14 gly glycosylation 1215:1227 arg2 Asn 1252:1254 the Asn 1248:1254 the Asn (N) of 92 site of this cytokine 1248:1286 Glycosidase digestion analysis determined that bcIFNb was modified with N-linked glycosylation, which occurred on the Asn (N) of 92 site of this cytokine. 29284145 9 14 gly glycosylation 1215:1227 arg2 N 1257:1257 N 1257:1257 N 1257:1257 Glycosidase digestion analysis determined that bcIFNb was modified with N-linked glycosylation, which occurred on the Asn (N) of 92 site of this cytokine. 29284145 10 15 theme type 1384:1387 arg1 bcIFNb 1389:1394 wild type bcIFNb 1379:1394 wild type bcIFNb 1379:1394 The un-glycosylated mutant bcIFNb-N92Q presented the similar antiviral ability as that of wild type bcIFNb, which demonstrated that N-linked glycosylation did not contribute directly to the antiviral property of this fish cytokine. 29284145 3 16 theme predicted 395:403 arg1 protein 412:418 the predicted bcIFNb protein 391:418 the predicted bcIFNb protein 391:418 The full-length cDNA of bcIFNb gene consists of 806 nucleotides and the predicted bcIFNb protein contains 188 amino acids. 29284145 1 17 theme important 134:142 arg1 role 144:147 an important role 131:147 an important role 131:147 Type I interferons (IFN-Is) play an important role in the antiviral immune response in teleost fishes. 29284145 8 18 theme bcIFNb-containing 1067:1083 arg1 media 1097:1101 the bcIFNb-containing conditioned media 1063:1101 the bcIFNb-containing conditioned media before GCRV or SVCV infection 1063:1131 EPC cells showed greatly enhanced antiviral ability when the cells were transfected with bcIFNb or treated with the bcIFNb-containing conditioned media before GCRV or SVCV infection. 29284145 8 19 theme EPC 951:953 arg1 cells 955:959 EPC cells 951:959 EPC cells 951:959 EPC cells showed greatly enhanced antiviral ability when the cells were transfected with bcIFNb or treated with the bcIFNb-containing conditioned media before GCRV or SVCV infection. 29284145 6 20 theme whole 695:699 arg1 lysate 706:711 the whole cell lysate 691:711 the whole cell lysate 691:711 bcIFNb was detected in both the whole cell lysate and the supernatant media of HEK293T cells or EPC cells transfected with bcIFNb through immunoblot assay. 29284145 2 21 theme type 220:223 arg1 interferon 227:236 one type I interferon 216:236 one type I interferon (bcIFNb) from black carp (Mylopharyngodon piceus) 216:286 In this study, one type I interferon (bcIFNb) from black carp (Mylopharyngodon piceus) has been cloned and characterized. 29284145 2 21 theme type 220:223 arg1 bcIFNb 239:244 bcIFNb 239:244 bcIFNb 239:244 In this study, one type I interferon (bcIFNb) from black carp (Mylopharyngodon piceus) has been cloned and characterized. 29284145 8 22 theme conditioned 1085:1095 arg1 media 1097:1101 the bcIFNb-containing conditioned media 1063:1101 the bcIFNb-containing conditioned media before GCRV or SVCV infection 1063:1131 EPC cells showed greatly enhanced antiviral ability when the cells were transfected with bcIFNb or treated with the bcIFNb-containing conditioned media before GCRV or SVCV infection. 29284145 3 23 contain contains 420:427 arg2 acids 439:443 188 amino acids 429:443 188 amino acids 429:443 The full-length cDNA of bcIFNb gene consists of 806 nucleotides and the predicted bcIFNb protein contains 188 amino acids. 29284145 3 23 contain contains 420:427 arg1 protein 412:418 the predicted bcIFNb protein 391:418 the predicted bcIFNb protein 391:418 The full-length cDNA of bcIFNb gene consists of 806 nucleotides and the predicted bcIFNb protein contains 188 amino acids. 29284145 5 24 theme q-PCR 551:555 arg1 analysis 557:564 q-PCR analysis 551:564 q-PCR analysis 551:564 q-PCR analysis demonstrated that bcIFNb mRNA level varied in vivo and ex vivo in response to different stimuli. 29284145 2 25 theme black 252:256 arg1 carp 258:261 black carp 252:261 black carp (Mylopharyngodon piceus) 252:286 In this study, one type I interferon (bcIFNb) from black carp (Mylopharyngodon piceus) has been cloned and characterized. 29284145 2 25 theme black 252:256 arg1 piceus 280:285 Mylopharyngodon piceus 264:285 Mylopharyngodon piceus 264:285 In this study, one type I interferon (bcIFNb) from black carp (Mylopharyngodon piceus) has been cloned and characterized. 29284145 3 26 theme gene 354:357 arg1 cDNA 339:342 The full-length cDNA 323:342 The full-length cDNA of bcIFNb gene 323:357 The full-length cDNA of bcIFNb gene consists of 806 nucleotides and the predicted bcIFNb protein contains 188 amino acids. 29284145 10 27 theme cytokine 1511:1518 arg1 property 1489:1496 the antiviral property 1475:1496 the antiviral property of this fish cytokine 1475:1518 The un-glycosylated mutant bcIFNb-N92Q presented the similar antiviral ability as that of wild type bcIFNb, which demonstrated that N-linked glycosylation did not contribute directly to the antiviral property of this fish cytokine. 29284145 4 28 theme evolutionary 480:491 arg1 position 493:500 evolutionary position 480:500 evolutionary position 480:500 Basing on the cysteine number and evolutionary position, bcIFNb was classified into group II type I IFN. 29284145 7 29 theme stimulated 823:832 arg1 ISGs 841:844 ISGs 841:844 ISGs 841:844 IFN stimulated genes (ISGs) were greatly upregulated when the host cells were treated with the bcIFNb-containing conditioned media. 29284145 7 29 theme stimulated 823:832 arg1 genes 834:838 IFN stimulated genes 819:838 IFN stimulated genes (ISGs) 819:845 IFN stimulated genes (ISGs) were greatly upregulated when the host cells were treated with the bcIFNb-containing conditioned media. 29284145 10 30 link N-linked 1421:1428 arg1 glycosylation 1430:1442 N-linked glycosylation 1421:1442 N-linked glycosylation 1421:1442 The un-glycosylated mutant bcIFNb-N92Q presented the similar antiviral ability as that of wild type bcIFNb, which demonstrated that N-linked glycosylation did not contribute directly to the antiviral property of this fish cytokine. 29284145 0 31 theme carp 14:17 arg1 IFNb 0:3 IFNb 0:3 IFNb of black carp 0:17 IFNb of black carp functions importantly in host innate immune response as an antiviral cytokine. 29284145 0 31 theme carp 14:17 arg1 cytokine 88:95 an antiviral cytokine 75:95 an antiviral cytokine 75:95 IFNb of black carp functions importantly in host innate immune response as an antiviral cytokine. 29284145 8 32 theme antiviral 985:993 arg1 ability 995:1001 greatly enhanced antiviral ability 968:1001 greatly enhanced antiviral ability 968:1001 EPC cells showed greatly enhanced antiviral ability when the cells were transfected with bcIFNb or treated with the bcIFNb-containing conditioned media before GCRV or SVCV infection. 29284145 6 33 theme cell 701:704 arg1 lysate 706:711 the whole cell lysate 691:711 the whole cell lysate 691:711 bcIFNb was detected in both the whole cell lysate and the supernatant media of HEK293T cells or EPC cells transfected with bcIFNb through immunoblot assay. 29284145 1 34 theme antiviral 156:164 arg1 response 173:180 the antiviral immune response 152:180 the antiviral immune response in teleost fishes 152:198 Type I interferons (IFN-Is) play an important role in the antiviral immune response in teleost fishes. 29284145 0 35 theme black 8:12 arg1 carp 14:17 black carp 8:17 black carp 8:17 IFNb of black carp functions importantly in host innate immune response as an antiviral cytokine. 29284145 8 36 theme enhanced 976:983 arg1 ability 995:1001 greatly enhanced antiviral ability 968:1001 greatly enhanced antiviral ability 968:1001 EPC cells showed greatly enhanced antiviral ability when the cells were transfected with bcIFNb or treated with the bcIFNb-containing conditioned media before GCRV or SVCV infection. 29284145 6 37 theme cells 763:767 arg1 lysate 706:711 the whole cell lysate 691:711 the whole cell lysate 691:711 bcIFNb was detected in both the whole cell lysate and the supernatant media of HEK293T cells or EPC cells transfected with bcIFNb through immunoblot assay. 29284145 6 37 theme cells 763:767 arg1 media 733:737 the supernatant media 717:737 the supernatant media of HEK293T cells or EPC cells transfected with bcIFNb through immunoblot assay 717:816 bcIFNb was detected in both the whole cell lysate and the supernatant media of HEK293T cells or EPC cells transfected with bcIFNb through immunoblot assay. 29284145 9 38 link N-linked 1206:1213 arg1 glycosylation 1215:1227 N-linked glycosylation 1206:1227 N-linked glycosylation 1206:1227 Glycosidase digestion analysis determined that bcIFNb was modified with N-linked glycosylation, which occurred on the Asn (N) of 92 site of this cytokine. 29284145 1 39 theme immune 166:171 arg1 response 173:180 the antiviral immune response 152:180 the antiviral immune response in teleost fishes 152:198 Type I interferons (IFN-Is) play an important role in the antiviral immune response in teleost fishes. 29284145 10 40 theme antiviral 1479:1487 arg1 property 1489:1496 the antiviral property 1475:1496 the antiviral property of this fish cytokine 1475:1518 The un-glycosylated mutant bcIFNb-N92Q presented the similar antiviral ability as that of wild type bcIFNb, which demonstrated that N-linked glycosylation did not contribute directly to the antiviral property of this fish cytokine. 29284145 2 41 theme Mylopharyngodon 264:278 arg1 carp 258:261 black carp 252:261 black carp (Mylopharyngodon piceus) 252:286 In this study, one type I interferon (bcIFNb) from black carp (Mylopharyngodon piceus) has been cloned and characterized. 29284145 2 41 theme Mylopharyngodon 264:278 arg1 piceus 280:285 Mylopharyngodon piceus 264:285 Mylopharyngodon piceus 264:285 In this study, one type I interferon (bcIFNb) from black carp (Mylopharyngodon piceus) has been cloned and characterized. 29284145 6 42 theme EPC 759:761 arg1 cells 763:767 EPC cells 759:767 EPC cells 759:767 bcIFNb was detected in both the whole cell lysate and the supernatant media of HEK293T cells or EPC cells transfected with bcIFNb through immunoblot assay. 29284145 3 43 theme bcIFNb 347:352 arg1 gene 354:357 bcIFNb gene 347:357 bcIFNb gene 347:357 The full-length cDNA of bcIFNb gene consists of 806 nucleotides and the predicted bcIFNb protein contains 188 amino acids. 29284145 10 44 theme mutant 1309:1314 arg1 bcIFNb-N92Q 1316:1326 The un-glycosylated mutant bcIFNb-N92Q 1289:1326 The un-glycosylated mutant bcIFNb-N92Q 1289:1326 The un-glycosylated mutant bcIFNb-N92Q presented the similar antiviral ability as that of wild type bcIFNb, which demonstrated that N-linked glycosylation did not contribute directly to the antiviral property of this fish cytokine. 29284145 6 45 located detected 674:681 arg1 lysate 706:711 the whole cell lysate 691:711 the whole cell lysate 691:711 bcIFNb was detected in both the whole cell lysate and the supernatant media of HEK293T cells or EPC cells transfected with bcIFNb through immunoblot assay. 29284145 6 45 located detected 674:681 arg2 bcIFNb 663:668 bcIFNb 663:668 bcIFNb 663:668 bcIFNb was detected in both the whole cell lysate and the supernatant media of HEK293T cells or EPC cells transfected with bcIFNb through immunoblot assay. 29284145 6 45 located detected 674:681 arg1 media 733:737 the supernatant media 717:737 the supernatant media of HEK293T cells or EPC cells transfected with bcIFNb through immunoblot assay 717:816 bcIFNb was detected in both the whole cell lysate and the supernatant media of HEK293T cells or EPC cells transfected with bcIFNb through immunoblot assay. 29284145 10 46 theme fish 1506:1509 arg1 cytokine 1511:1518 this fish cytokine 1501:1518 this fish cytokine 1501:1518 The un-glycosylated mutant bcIFNb-N92Q presented the similar antiviral ability as that of wild type bcIFNb, which demonstrated that N-linked glycosylation did not contribute directly to the antiviral property of this fish cytokine. 29284145 1 47 from response 173:180 arg1 fishes 193:198 teleost fishes 185:198 teleost fishes 185:198 Type I interferons (IFN-Is) play an important role in the antiviral immune response in teleost fishes. 29284145 0 48 theme host 44:47 arg1 response 63:70 host innate immune response 44:70 host innate immune response 44:70 IFNb of black carp functions importantly in host innate immune response as an antiviral cytokine. 29284145 9 49 theme site 1266:1269 arg1 N 1257:1257 N 1257:1257 N 1257:1257 Glycosidase digestion analysis determined that bcIFNb was modified with N-linked glycosylation, which occurred on the Asn (N) of 92 site of this cytokine. 29284145 9 49 theme site 1266:1269 arg1 Asn 1252:1254 the Asn 1248:1254 the Asn (N) of 92 site of this cytokine 1248:1286 Glycosidase digestion analysis determined that bcIFNb was modified with N-linked glycosylation, which occurred on the Asn (N) of 92 site of this cytokine. 29284145 8 50 theme SVCV 1118:1121 arg1 infection 1123:1131 SVCV infection 1118:1131 SVCV infection 1118:1131 EPC cells showed greatly enhanced antiviral ability when the cells were transfected with bcIFNb or treated with the bcIFNb-containing conditioned media before GCRV or SVCV infection. 29284145 6 51 theme cells 750:754 arg1 lysate 706:711 the whole cell lysate 691:711 the whole cell lysate 691:711 bcIFNb was detected in both the whole cell lysate and the supernatant media of HEK293T cells or EPC cells transfected with bcIFNb through immunoblot assay. 29284145 6 51 theme cells 750:754 arg1 media 733:737 the supernatant media 717:737 the supernatant media of HEK293T cells or EPC cells transfected with bcIFNb through immunoblot assay 717:816 bcIFNb was detected in both the whole cell lysate and the supernatant media of HEK293T cells or EPC cells transfected with bcIFNb through immunoblot assay. 29284145 9 52 theme Glycosidase 1134:1144 arg1 analysis 1156:1163 Glycosidase digestion analysis 1134:1163 Glycosidase digestion analysis 1134:1163 Glycosidase digestion analysis determined that bcIFNb was modified with N-linked glycosylation, which occurred on the Asn (N) of 92 site of this cytokine. 29284145 1 53 theme Type 98:101 arg1 interferons 105:115 Type I interferons 98:115 Type I interferons (IFN-Is) 98:124 Type I interferons (IFN-Is) play an important role in the antiviral immune response in teleost fishes. 29284145 1 53 theme Type 98:101 arg1 IFN-Is 118:123 IFN-Is 118:123 IFN-Is 118:123 Type I interferons (IFN-Is) play an important role in the antiviral immune response in teleost fishes. 29284145 9 54 mod modified 1192:1199 arg3 glycosylation 1215:1227 N-linked glycosylation 1206:1227 N-linked glycosylation 1206:1227 Glycosidase digestion analysis determined that bcIFNb was modified with N-linked glycosylation, which occurred on the Asn (N) of 92 site of this cytokine. 29284145 9 54 mod modified 1192:1199 arg1 bcIFNb 1181:1186 bcIFNb 1181:1186 bcIFNb 1181:1186 Glycosidase digestion analysis determined that bcIFNb was modified with N-linked glycosylation, which occurred on the Asn (N) of 92 site of this cytokine. 29284145 6 55 theme HEK293T 742:748 arg1 cells 750:754 HEK293T cells 742:754 HEK293T cells 742:754 bcIFNb was detected in both the whole cell lysate and the supernatant media of HEK293T cells or EPC cells transfected with bcIFNb through immunoblot assay. 29284145 10 56 theme wild 1379:1382 arg1 bcIFNb 1389:1394 wild type bcIFNb 1379:1394 wild type bcIFNb 1379:1394 The un-glycosylated mutant bcIFNb-N92Q presented the similar antiviral ability as that of wild type bcIFNb, which demonstrated that N-linked glycosylation did not contribute directly to the antiviral property of this fish cytokine. 29284145 1 57 theme I 103:103 arg1 interferons 105:115 Type I interferons 98:115 Type I interferons (IFN-Is) 98:124 Type I interferons (IFN-Is) play an important role in the antiviral immune response in teleost fishes. 29284145 1 57 theme I 103:103 arg1 IFN-Is 118:123 IFN-Is 118:123 IFN-Is 118:123 Type I interferons (IFN-Is) play an important role in the antiviral immune response in teleost fishes. 29284145 4 58 theme cysteine 460:467 arg1 number 469:474 the cysteine number 456:474 the cysteine number 456:474 Basing on the cysteine number and evolutionary position, bcIFNb was classified into group II type I IFN. 29284145 7 59 theme bcIFNb-containing 914:930 arg1 media 944:948 the bcIFNb-containing conditioned media 910:948 the bcIFNb-containing conditioned media 910:948 IFN stimulated genes (ISGs) were greatly upregulated when the host cells were treated with the bcIFNb-containing conditioned media. 29284145 3 60 theme bcIFNb 405:410 arg1 protein 412:418 the predicted bcIFNb protein 391:418 the predicted bcIFNb protein 391:418 The full-length cDNA of bcIFNb gene consists of 806 nucleotides and the predicted bcIFNb protein contains 188 amino acids. 29284145 7 61 theme IFN 819:821 arg1 ISGs 841:844 ISGs 841:844 ISGs 841:844 IFN stimulated genes (ISGs) were greatly upregulated when the host cells were treated with the bcIFNb-containing conditioned media. 29284145 7 61 theme IFN 819:821 arg1 genes 834:838 IFN stimulated genes 819:838 IFN stimulated genes (ISGs) 819:845 IFN stimulated genes (ISGs) were greatly upregulated when the host cells were treated with the bcIFNb-containing conditioned media. 29284145 1 62 theme teleost 185:191 arg1 fishes 193:198 teleost fishes 185:198 teleost fishes 185:198 Type I interferons (IFN-Is) play an important role in the antiviral immune response in teleost fishes. 29284145 7 63 theme conditioned 932:942 arg1 media 944:948 the bcIFNb-containing conditioned media 910:948 the bcIFNb-containing conditioned media 910:948 IFN stimulated genes (ISGs) were greatly upregulated when the host cells were treated with the bcIFNb-containing conditioned media. 29284145 7 64 theme host 881:884 arg1 cells 886:890 the host cells 877:890 the host cells 877:890 IFN stimulated genes (ISGs) were greatly upregulated when the host cells were treated with the bcIFNb-containing conditioned media. 29284145 4 65 theme group 530:534 arg1 IFN 546:548 group II type I IFN 530:548 group II type I IFN 530:548 Basing on the cysteine number and evolutionary position, bcIFNb was classified into group II type I IFN. 29284145 0 66 theme immune 56:61 arg1 response 63:70 host innate immune response 44:70 host innate immune response 44:70 IFNb of black carp functions importantly in host innate immune response as an antiviral cytokine. 29284145 6 67 theme supernatant 721:731 arg1 media 733:737 the supernatant media 717:737 the supernatant media of HEK293T cells or EPC cells transfected with bcIFNb through immunoblot assay 717:816 bcIFNb was detected in both the whole cell lysate and the supernatant media of HEK293T cells or EPC cells transfected with bcIFNb through immunoblot assay. 29284145 10 68 theme N-linked 1421:1428 arg1 glycosylation 1430:1442 N-linked glycosylation 1421:1442 N-linked glycosylation 1421:1442 The un-glycosylated mutant bcIFNb-N92Q presented the similar antiviral ability as that of wild type bcIFNb, which demonstrated that N-linked glycosylation did not contribute directly to the antiviral property of this fish cytokine. 29284145 0 69 theme innate 49:54 arg1 response 63:70 host innate immune response 44:70 host innate immune response 44:70 IFNb of black carp functions importantly in host innate immune response as an antiviral cytokine. 29284145 9 70 theme N-linked 1206:1213 arg1 glycosylation 1215:1227 N-linked glycosylation 1206:1227 N-linked glycosylation 1206:1227 Glycosidase digestion analysis determined that bcIFNb was modified with N-linked glycosylation, which occurred on the Asn (N) of 92 site of this cytokine. 29284145 9 71 theme cytokine 1279:1286 arg1 site 1266:1269 92 site 1263:1269 92 site of this cytokine 1263:1286 Glycosidase digestion analysis determined that bcIFNb was modified with N-linked glycosylation, which occurred on the Asn (N) of 92 site of this cytokine. 29284145 9 71 theme cytokine 1279:1286 arg1 cytokine 1279:1286 this cytokine 1274:1286 this cytokine 1274:1286 Glycosidase digestion analysis determined that bcIFNb was modified with N-linked glycosylation, which occurred on the Asn (N) of 92 site of this cytokine. 29284145 4 72 theme type 539:542 arg1 IFN 546:548 group II type I IFN 530:548 group II type I IFN 530:548 Basing on the cysteine number and evolutionary position, bcIFNb was classified into group II type I IFN. 28395449 0 0 theme cells 102:106 arg1 behaviors 50:58 the biological behaviors 35:58 the biological behaviors 35:58 [O-GlcNAc glycosylation influences the biological behaviors and etoposide-induced apoptosis of Nalm-6 cells]. 28395449 0 0 theme cells 102:106 arg1 apoptosis 82:90 etoposide-induced apoptosis 64:90 etoposide-induced apoptosis of Nalm-6 cells] 64:107 [O-GlcNAc glycosylation influences the biological behaviors and etoposide-induced apoptosis of Nalm-6 cells]. 28395449 6 1 theme proliferation 1097:1109 arg1 capacity 1111:1118 down the proliferation capacity 1088:1118 down the proliferation capacity 1088:1118 Results: With the concentration of Vp16 increasing, the O-GlcNAc modified levels of total protein and the expression of OGT were up regulated (P<0.05, n=6) ; Alloxan could slow down the proliferation capacity, induce apoptosis[ (15.190±2.539) % vs (21.910±4.105) %, P=0.007], arrest cell cycle[G1 phase: (43.534±4.453) % vs (57.322±6.091) %, P=0.003; S phase: (50.747±5.937) % vs (37.201±4.661) %, P=0.001]. 28395449 8 2 theme modified 1576:1583 arg1 level 1585:1589 O-GlcNAc modified level 1567:1589 O-GlcNAc modified level of Nalm-6 cells 1567:1605 Conclusion: Changes of O-GlcNAc modified level of Nalm-6 cells along with the inhibition of OGT could influence the biological behaviors and inhibit apoptosis induced by Vp16. 28395449 1 3 theme glycosylation 156:168 arg1 effects 136:142 the effects 132:142 the effects of O-GlcNAc glycosylation and its key enzyme OGT on the biological behaviors and etoposide (Vp16) -induced apoptosis of Nalm-6 cells 132:275 Objective: To explore the effects of O-GlcNAc glycosylation and its key enzyme OGT on the biological behaviors and etoposide (Vp16) -induced apoptosis of Nalm-6 cells. 28395449 6 4 theme S 1262:1262 arg1 phase 1264:1268 S phase 1262:1268 P=0.003; S phase 1253:1268 Results: With the concentration of Vp16 increasing, the O-GlcNAc modified levels of total protein and the expression of OGT were up regulated (P<0.05, n=6) ; Alloxan could slow down the proliferation capacity, induce apoptosis[ (15.190±2.539) % vs (21.910±4.105) %, P=0.007], arrest cell cycle[G1 phase: (43.534±4.453) % vs (57.322±6.091) %, P=0.003; S phase: (50.747±5.937) % vs (37.201±4.661) %, P=0.001]. 28395449 0 5 theme Nalm-6 95:100 arg1 cells 102:106 Nalm-6 cells 95:106 Nalm-6 cells 95:106 [O-GlcNAc glycosylation influences the biological behaviors and etoposide-induced apoptosis of Nalm-6 cells]. 28395449 3 6 from influence 383:391 arg1 proliferation 420:432 Nalm-6 cells proliferation 407:432 Nalm-6 cells proliferation 407:432 The influence of Alloxan on Nalm-6 cells proliferation was checked by CCK-8 assay, apoptosis and cell cycle by flow cytometry. 28395449 3 7 theme cell 476:479 arg1 cycle 481:485 cell cycle 476:485 cell cycle 476:485 The influence of Alloxan on Nalm-6 cells proliferation was checked by CCK-8 assay, apoptosis and cell cycle by flow cytometry. 28395449 7 8 dep Bcl-2 1487:1491 arg1 0.454±0.125 1505:1515 0.454±0.125 1505:1515 0.454±0.125 1505:1515 Alloxan could inhibit the apoptosis caused by Vp16[ (75.195±13.845) % vs (52.741±10.815) %, P=0.011]along with Bax decreasing (5.496±1.998 vs 2.950±0.703, P=0.015) and Bcl-2 increasing (0.454±0.125 vs 0.803±0.223, P=0.013) . 28395449 7 8 dep Bcl-2 1487:1491 arg1 P=0.013 1533:1539 P=0.013 1533:1539 P=0.013 1533:1539 Alloxan could inhibit the apoptosis caused by Vp16[ (75.195±13.845) % vs (52.741±10.815) %, P=0.011]along with Bax decreasing (5.496±1.998 vs 2.950±0.703, P=0.015) and Bcl-2 increasing (0.454±0.125 vs 0.803±0.223, P=0.013) . 28395449 7 8 dep Bcl-2 1487:1491 arg1 0.803±0.223 1520:1530 0.803±0.223 1520:1530 0.803±0.223 1520:1530 Alloxan could inhibit the apoptosis caused by Vp16[ (75.195±13.845) % vs (52.741±10.815) %, P=0.011]along with Bax decreasing (5.496±1.998 vs 2.950±0.703, P=0.015) and Bcl-2 increasing (0.454±0.125 vs 0.803±0.223, P=0.013) . 28395449 1 9 theme -induced 242:249 arg1 apoptosis 251:259 etoposide (Vp16) -induced apoptosis 225:259 etoposide (Vp16) -induced apoptosis 225:259 Objective: To explore the effects of O-GlcNAc glycosylation and its key enzyme OGT on the biological behaviors and etoposide (Vp16) -induced apoptosis of Nalm-6 cells. 28395449 6 10 theme cycle[G1 1199:1206 arg1 phase 1208:1212 arrest cell cycle[G1 phase 1187:1212 arrest cell cycle[G1 phase 1187:1212 Results: With the concentration of Vp16 increasing, the O-GlcNAc modified levels of total protein and the expression of OGT were up regulated (P<0.05, n=6) ; Alloxan could slow down the proliferation capacity, induce apoptosis[ (15.190±2.539) % vs (21.910±4.105) %, P=0.007], arrest cell cycle[G1 phase: (43.534±4.453) % vs (57.322±6.091) %, P=0.003; S phase: (50.747±5.937) % vs (37.201±4.661) %, P=0.001]. 28395449 7 11 theme increasing 1493:1502 arg1 Bcl-2 1487:1491 Bcl-2 increasing 1487:1502 Bcl-2 increasing (0.454±0.125 vs 0.803±0.223, P=0.013) 1487:1540 Alloxan could inhibit the apoptosis caused by Vp16[ (75.195±13.845) % vs (52.741±10.815) %, P=0.011]along with Bax decreasing (5.496±1.998 vs 2.950±0.703, P=0.015) and Bcl-2 increasing (0.454±0.125 vs 0.803±0.223, P=0.013) . 28395449 7 12 theme decreasing 1434:1443 arg1 Bax 1430:1432 Bax decreasing 1430:1443 Bax decreasing (5.496±1.998 vs 2.950±0.703, P=0.015) 1430:1481 Alloxan could inhibit the apoptosis caused by Vp16[ (75.195±13.845) % vs (52.741±10.815) %, P=0.011]along with Bax decreasing (5.496±1.998 vs 2.950±0.703, P=0.015) and Bcl-2 increasing (0.454±0.125 vs 0.803±0.223, P=0.013) . 28395449 4 13 theme Vp16 565:568 arg1 concentrations 547:560 different concentrations 537:560 different concentrations of Vp16 537:568 Nalm-6 cells were treated with different concentrations of Vp16 for 12 h, and then the O-GlcNAc level and the expressions of OGT were examined by Western blot. 28395449 6 14 theme cell 1194:1197 arg1 phase 1208:1212 arrest cell cycle[G1 phase 1187:1212 arrest cell cycle[G1 phase 1187:1212 Results: With the concentration of Vp16 increasing, the O-GlcNAc modified levels of total protein and the expression of OGT were up regulated (P<0.05, n=6) ; Alloxan could slow down the proliferation capacity, induce apoptosis[ (15.190±2.539) % vs (21.910±4.105) %, P=0.007], arrest cell cycle[G1 phase: (43.534±4.453) % vs (57.322±6.091) %, P=0.003; S phase: (50.747±5.937) % vs (37.201±4.661) %, P=0.001]. 28395449 5 15 with μg/ml 721:725 arg1 Alloxan 693:699 Alloxan 693:699 Alloxan 693:699 After treating Nalm-6 with Alloxan for 24 h and then 5 μg/ml of Vp16 for 12 h, the apoptosis of different groups were measured with flow cytometry, and the expression of apoptosis-associated proteins Bax and Bcl-2 were examined by Western blot. 28395449 5 16 theme flow 798:801 arg1 cytometry 803:811 flow cytometry 798:811 flow cytometry 798:811 After treating Nalm-6 with Alloxan for 24 h and then 5 μg/ml of Vp16 for 12 h, the apoptosis of different groups were measured with flow cytometry, and the expression of apoptosis-associated proteins Bax and Bcl-2 were examined by Western blot. 28395449 6 17 theme arrest 1187:1192 arg1 phase 1208:1212 arrest cell cycle[G1 phase 1187:1212 arrest cell cycle[G1 phase 1187:1212 Results: With the concentration of Vp16 increasing, the O-GlcNAc modified levels of total protein and the expression of OGT were up regulated (P<0.05, n=6) ; Alloxan could slow down the proliferation capacity, induce apoptosis[ (15.190±2.539) % vs (21.910±4.105) %, P=0.007], arrest cell cycle[G1 phase: (43.534±4.453) % vs (57.322±6.091) %, P=0.003; S phase: (50.747±5.937) % vs (37.201±4.661) %, P=0.001]. 28395449 8 18 theme cells 1601:1605 arg1 level 1585:1589 O-GlcNAc modified level 1567:1589 O-GlcNAc modified level of Nalm-6 cells 1567:1605 Conclusion: Changes of O-GlcNAc modified level of Nalm-6 cells along with the inhibition of OGT could influence the biological behaviors and inhibit apoptosis induced by Vp16. 28395449 6 19 theme Vp16 946:949 arg1 concentration 929:941 the concentration 925:941 the concentration of Vp16 increasing 925:960 Results: With the concentration of Vp16 increasing, the O-GlcNAc modified levels of total protein and the expression of OGT were up regulated (P<0.05, n=6) ; Alloxan could slow down the proliferation capacity, induce apoptosis[ (15.190±2.539) % vs (21.910±4.105) %, P=0.007], arrest cell cycle[G1 phase: (43.534±4.453) % vs (57.322±6.091) %, P=0.003; S phase: (50.747±5.937) % vs (37.201±4.661) %, P=0.001]. 28395449 3 20 theme flow 490:493 arg1 cytometry 495:503 flow cytometry 490:503 flow cytometry 490:503 The influence of Alloxan on Nalm-6 cells proliferation was checked by CCK-8 assay, apoptosis and cell cycle by flow cytometry. 28395449 3 21 theme Alloxan 396:402 arg1 influence 383:391 The influence 379:391 The influence of Alloxan on Nalm-6 cells proliferation 379:432 The influence of Alloxan on Nalm-6 cells proliferation was checked by CCK-8 assay, apoptosis and cell cycle by flow cytometry. 28395449 2 22 theme OGT 374:376 arg1 Alloxan 349:355 Alloxan 349:355 Alloxan 349:355 Methods: Low O-GlcNAc modified Nalm-6 cells model was established with Alloxan, an inhibitor of OGT. 28395449 2 22 theme OGT 374:376 arg1 inhibitor 361:369 an inhibitor 358:369 an inhibitor of OGT 358:376 Methods: Low O-GlcNAc modified Nalm-6 cells model was established with Alloxan, an inhibitor of OGT. 28395449 8 23 theme Nalm-6 1594:1599 arg1 cells 1601:1605 Nalm-6 cells 1594:1605 Nalm-6 cells 1594:1605 Conclusion: Changes of O-GlcNAc modified level of Nalm-6 cells along with the inhibition of OGT could influence the biological behaviors and inhibit apoptosis induced by Vp16. 28395449 5 24 dep proteins 857:864 arg1 proteins 857:864 apoptosis-associated proteins 836:864 apoptosis-associated proteins Bax and Bcl-2 836:878 After treating Nalm-6 with Alloxan for 24 h and then 5 μg/ml of Vp16 for 12 h, the apoptosis of different groups were measured with flow cytometry, and the expression of apoptosis-associated proteins Bax and Bcl-2 were examined by Western blot. 28395449 5 24 dep proteins 857:864 arg1 Bcl-2 874:878 Bcl-2 874:878 Bcl-2 874:878 After treating Nalm-6 with Alloxan for 24 h and then 5 μg/ml of Vp16 for 12 h, the apoptosis of different groups were measured with flow cytometry, and the expression of apoptosis-associated proteins Bax and Bcl-2 were examined by Western blot. 28395449 5 24 dep proteins 857:864 arg1 Bax 866:868 Bax 866:868 Bax 866:868 After treating Nalm-6 with Alloxan for 24 h and then 5 μg/ml of Vp16 for 12 h, the apoptosis of different groups were measured with flow cytometry, and the expression of apoptosis-associated proteins Bax and Bcl-2 were examined by Western blot. 28395449 5 25 theme Vp16 730:733 arg1 Nalm-6 681:686 Nalm-6 681:686 Nalm-6 with Alloxan for 24 h 681:708 After treating Nalm-6 with Alloxan for 24 h and then 5 μg/ml of Vp16 for 12 h, the apoptosis of different groups were measured with flow cytometry, and the expression of apoptosis-associated proteins Bax and Bcl-2 were examined by Western blot. 28395449 5 25 theme Vp16 730:733 arg1 μg/ml 721:725 then 5 μg/ml 714:725 then 5 μg/ml of Vp16 for 12 h 714:742 After treating Nalm-6 with Alloxan for 24 h and then 5 μg/ml of Vp16 for 12 h, the apoptosis of different groups were measured with flow cytometry, and the expression of apoptosis-associated proteins Bax and Bcl-2 were examined by Western blot. 28395449 6 26 dep P=0.003 1253:1259 arg1 phase 1264:1268 S phase 1262:1268 P=0.003; S phase 1253:1268 Results: With the concentration of Vp16 increasing, the O-GlcNAc modified levels of total protein and the expression of OGT were up regulated (P<0.05, n=6) ; Alloxan could slow down the proliferation capacity, induce apoptosis[ (15.190±2.539) % vs (21.910±4.105) %, P=0.007], arrest cell cycle[G1 phase: (43.534±4.453) % vs (57.322±6.091) %, P=0.003; S phase: (50.747±5.937) % vs (37.201±4.661) %, P=0.001]. 28395449 1 27 theme key 178:180 arg1 OGT 189:191 its key enzyme OGT 174:191 its key enzyme OGT 174:191 Objective: To explore the effects of O-GlcNAc glycosylation and its key enzyme OGT on the biological behaviors and etoposide (Vp16) -induced apoptosis of Nalm-6 cells. 28395449 6 28 dep induce 1121:1126 arg1 P=0.007 1177:1183 P=0.007 1177:1183 P=0.007 1177:1183 Results: With the concentration of Vp16 increasing, the O-GlcNAc modified levels of total protein and the expression of OGT were up regulated (P<0.05, n=6) ; Alloxan could slow down the proliferation capacity, induce apoptosis[ (15.190±2.539) % vs (21.910±4.105) %, P=0.007], arrest cell cycle[G1 phase: (43.534±4.453) % vs (57.322±6.091) %, P=0.003; S phase: (50.747±5.937) % vs (37.201±4.661) %, P=0.001]. 28395449 6 29 theme modified 976:983 arg1 levels 985:990 the O-GlcNAc modified levels 963:990 the O-GlcNAc modified levels of total protein 963:1007 Results: With the concentration of Vp16 increasing, the O-GlcNAc modified levels of total protein and the expression of OGT were up regulated (P<0.05, n=6) ; Alloxan could slow down the proliferation capacity, induce apoptosis[ (15.190±2.539) % vs (21.910±4.105) %, P=0.007], arrest cell cycle[G1 phase: (43.534±4.453) % vs (57.322±6.091) %, P=0.003; S phase: (50.747±5.937) % vs (37.201±4.661) %, P=0.001]. 28395449 1 30 from effects 136:142 arg1 apoptosis 251:259 etoposide (Vp16) -induced apoptosis 225:259 etoposide (Vp16) -induced apoptosis 225:259 Objective: To explore the effects of O-GlcNAc glycosylation and its key enzyme OGT on the biological behaviors and etoposide (Vp16) -induced apoptosis of Nalm-6 cells. 28395449 1 30 from effects 136:142 arg1 behaviors 211:219 the biological behaviors 196:219 the biological behaviors 196:219 Objective: To explore the effects of O-GlcNAc glycosylation and its key enzyme OGT on the biological behaviors and etoposide (Vp16) -induced apoptosis of Nalm-6 cells. 28395449 2 31 theme modified 300:307 arg1 model 322:326 Low O-GlcNAc modified Nalm-6 cells model 287:326 Low O-GlcNAc modified Nalm-6 cells model 287:326 Methods: Low O-GlcNAc modified Nalm-6 cells model was established with Alloxan, an inhibitor of OGT. 28395449 1 32 theme enzyme 182:187 arg1 OGT 189:191 its key enzyme OGT 174:191 its key enzyme OGT 174:191 Objective: To explore the effects of O-GlcNAc glycosylation and its key enzyme OGT on the biological behaviors and etoposide (Vp16) -induced apoptosis of Nalm-6 cells. 28395449 0 33 theme [O-GlcNAc 0:8 arg1 glycosylation 10:22 [O-GlcNAc glycosylation 0:22 [O-GlcNAc glycosylation 0:22 [O-GlcNAc glycosylation influences the biological behaviors and etoposide-induced apoptosis of Nalm-6 cells]. 28395449 1 34 theme Nalm-6 264:269 arg1 cells 271:275 Nalm-6 cells 264:275 Nalm-6 cells 264:275 Objective: To explore the effects of O-GlcNAc glycosylation and its key enzyme OGT on the biological behaviors and etoposide (Vp16) -induced apoptosis of Nalm-6 cells. 28395449 5 35 theme apoptosis-associated 836:855 arg1 proteins 857:864 apoptosis-associated proteins 836:864 apoptosis-associated proteins Bax and Bcl-2 836:878 After treating Nalm-6 with Alloxan for 24 h and then 5 μg/ml of Vp16 for 12 h, the apoptosis of different groups were measured with flow cytometry, and the expression of apoptosis-associated proteins Bax and Bcl-2 were examined by Western blot. 28395449 5 35 theme apoptosis-associated 836:855 arg1 Bcl-2 874:878 Bcl-2 874:878 Bcl-2 874:878 After treating Nalm-6 with Alloxan for 24 h and then 5 μg/ml of Vp16 for 12 h, the apoptosis of different groups were measured with flow cytometry, and the expression of apoptosis-associated proteins Bax and Bcl-2 were examined by Western blot. 28395449 5 35 theme apoptosis-associated 836:855 arg1 Bax 866:868 Bax 866:868 Bax 866:868 After treating Nalm-6 with Alloxan for 24 h and then 5 μg/ml of Vp16 for 12 h, the apoptosis of different groups were measured with flow cytometry, and the expression of apoptosis-associated proteins Bax and Bcl-2 were examined by Western blot. 28395449 1 36 theme OGT 189:191 arg1 effects 136:142 the effects 132:142 the effects of O-GlcNAc glycosylation and its key enzyme OGT on the biological behaviors and etoposide (Vp16) -induced apoptosis of Nalm-6 cells 132:275 Objective: To explore the effects of O-GlcNAc glycosylation and its key enzyme OGT on the biological behaviors and etoposide (Vp16) -induced apoptosis of Nalm-6 cells. 28395449 1 37 theme cells 271:275 arg1 apoptosis 251:259 etoposide (Vp16) -induced apoptosis 225:259 etoposide (Vp16) -induced apoptosis 225:259 Objective: To explore the effects of O-GlcNAc glycosylation and its key enzyme OGT on the biological behaviors and etoposide (Vp16) -induced apoptosis of Nalm-6 cells. 28395449 1 37 theme cells 271:275 arg1 behaviors 211:219 the biological behaviors 196:219 the biological behaviors 196:219 Objective: To explore the effects of O-GlcNAc glycosylation and its key enzyme OGT on the biological behaviors and etoposide (Vp16) -induced apoptosis of Nalm-6 cells. 28395449 5 38 theme proteins 857:864 arg1 expression 822:831 the expression 818:831 the expression of apoptosis-associated proteins Bax and Bcl-2 818:878 After treating Nalm-6 with Alloxan for 24 h and then 5 μg/ml of Vp16 for 12 h, the apoptosis of different groups were measured with flow cytometry, and the expression of apoptosis-associated proteins Bax and Bcl-2 were examined by Western blot. 28395449 6 39 theme O-GlcNAc 967:974 arg1 levels 985:990 the O-GlcNAc modified levels 963:990 the O-GlcNAc modified levels of total protein 963:1007 Results: With the concentration of Vp16 increasing, the O-GlcNAc modified levels of total protein and the expression of OGT were up regulated (P<0.05, n=6) ; Alloxan could slow down the proliferation capacity, induce apoptosis[ (15.190±2.539) % vs (21.910±4.105) %, P=0.007], arrest cell cycle[G1 phase: (43.534±4.453) % vs (57.322±6.091) %, P=0.003; S phase: (50.747±5.937) % vs (37.201±4.661) %, P=0.001]. 28395449 6 40 theme increasing 951:960 arg1 Vp16 946:949 Vp16 increasing 946:960 Vp16 increasing 946:960 Results: With the concentration of Vp16 increasing, the O-GlcNAc modified levels of total protein and the expression of OGT were up regulated (P<0.05, n=6) ; Alloxan could slow down the proliferation capacity, induce apoptosis[ (15.190±2.539) % vs (21.910±4.105) %, P=0.007], arrest cell cycle[G1 phase: (43.534±4.453) % vs (57.322±6.091) %, P=0.003; S phase: (50.747±5.937) % vs (37.201±4.661) %, P=0.001]. 28395449 6 41 theme OGT 1031:1033 arg1 levels 985:990 the O-GlcNAc modified levels 963:990 the O-GlcNAc modified levels of total protein 963:1007 Results: With the concentration of Vp16 increasing, the O-GlcNAc modified levels of total protein and the expression of OGT were up regulated (P<0.05, n=6) ; Alloxan could slow down the proliferation capacity, induce apoptosis[ (15.190±2.539) % vs (21.910±4.105) %, P=0.007], arrest cell cycle[G1 phase: (43.534±4.453) % vs (57.322±6.091) %, P=0.003; S phase: (50.747±5.937) % vs (37.201±4.661) %, P=0.001]. 28395449 6 41 theme OGT 1031:1033 arg1 expression 1017:1026 the expression 1013:1026 the expression of OGT 1013:1033 Results: With the concentration of Vp16 increasing, the O-GlcNAc modified levels of total protein and the expression of OGT were up regulated (P<0.05, n=6) ; Alloxan could slow down the proliferation capacity, induce apoptosis[ (15.190±2.539) % vs (21.910±4.105) %, P=0.007], arrest cell cycle[G1 phase: (43.534±4.453) % vs (57.322±6.091) %, P=0.003; S phase: (50.747±5.937) % vs (37.201±4.661) %, P=0.001]. 28395449 7 42 theme 52.741±10.815 1393:1405 arg1 % 1408:1408 (52.741±10.815) % 1392:1408 (52.741±10.815) %, P=0.011] 1392:1418 Alloxan could inhibit the apoptosis caused by Vp16[ (75.195±13.845) % vs (52.741±10.815) %, P=0.011]along with Bax decreasing (5.496±1.998 vs 2.950±0.703, P=0.015) and Bcl-2 increasing (0.454±0.125 vs 0.803±0.223, P=0.013) . 28395449 5 43 theme different 762:770 arg1 groups 772:777 different groups 762:777 different groups 762:777 After treating Nalm-6 with Alloxan for 24 h and then 5 μg/ml of Vp16 for 12 h, the apoptosis of different groups were measured with flow cytometry, and the expression of apoptosis-associated proteins Bax and Bcl-2 were examined by Western blot. 28395449 8 44 theme level 1585:1589 arg1 Changes 1556:1562 Changes 1556:1562 Changes of O-GlcNAc modified level of Nalm-6 cells along with the inhibition of OGT 1556:1638 Conclusion: Changes of O-GlcNAc modified level of Nalm-6 cells along with the inhibition of OGT could influence the biological behaviors and inhibit apoptosis induced by Vp16. 28395449 4 45 theme O-GlcNAc 593:600 arg1 level 602:606 then the O-GlcNAc level 584:606 then the O-GlcNAc level 584:606 Nalm-6 cells were treated with different concentrations of Vp16 for 12 h, and then the O-GlcNAc level and the expressions of OGT were examined by Western blot. 28395449 5 46 with Nalm-6 681:686 arg1 Alloxan 693:699 Alloxan 693:699 Alloxan 693:699 After treating Nalm-6 with Alloxan for 24 h and then 5 μg/ml of Vp16 for 12 h, the apoptosis of different groups were measured with flow cytometry, and the expression of apoptosis-associated proteins Bax and Bcl-2 were examined by Western blot. 28395449 1 47 theme biological 200:209 arg1 behaviors 211:219 the biological behaviors 196:219 the biological behaviors 196:219 Objective: To explore the effects of O-GlcNAc glycosylation and its key enzyme OGT on the biological behaviors and etoposide (Vp16) -induced apoptosis of Nalm-6 cells. 28395449 0 48 theme biological 39:48 arg1 behaviors 50:58 the biological behaviors 35:58 the biological behaviors 35:58 [O-GlcNAc glycosylation influences the biological behaviors and etoposide-induced apoptosis of Nalm-6 cells]. 28395449 4 49 theme different 537:545 arg1 concentrations 547:560 different concentrations 537:560 different concentrations of Vp16 537:568 Nalm-6 cells were treated with different concentrations of Vp16 for 12 h, and then the O-GlcNAc level and the expressions of OGT were examined by Western blot. 28395449 0 50 theme etoposide-induced 64:80 arg1 apoptosis 82:90 etoposide-induced apoptosis 64:90 etoposide-induced apoptosis of Nalm-6 cells] 64:107 [O-GlcNAc glycosylation influences the biological behaviors and etoposide-induced apoptosis of Nalm-6 cells]. 28395449 5 51 theme groups 772:777 arg1 apoptosis 749:757 the apoptosis 745:757 the apoptosis of different groups 745:777 After treating Nalm-6 with Alloxan for 24 h and then 5 μg/ml of Vp16 for 12 h, the apoptosis of different groups were measured with flow cytometry, and the expression of apoptosis-associated proteins Bax and Bcl-2 were examined by Western blot. 28395449 3 52 theme Nalm-6 407:412 arg1 cells 414:418 Nalm-6 cells 407:418 Nalm-6 cells proliferation 407:432 The influence of Alloxan on Nalm-6 cells proliferation was checked by CCK-8 assay, apoptosis and cell cycle by flow cytometry. 28395449 6 53 theme down 1088:1091 arg1 capacity 1111:1118 down the proliferation capacity 1088:1118 down the proliferation capacity 1088:1118 Results: With the concentration of Vp16 increasing, the O-GlcNAc modified levels of total protein and the expression of OGT were up regulated (P<0.05, n=6) ; Alloxan could slow down the proliferation capacity, induce apoptosis[ (15.190±2.539) % vs (21.910±4.105) %, P=0.007], arrest cell cycle[G1 phase: (43.534±4.453) % vs (57.322±6.091) %, P=0.003; S phase: (50.747±5.937) % vs (37.201±4.661) %, P=0.001]. 28395449 6 54 theme protein 1001:1007 arg1 levels 985:990 the O-GlcNAc modified levels 963:990 the O-GlcNAc modified levels of total protein 963:1007 Results: With the concentration of Vp16 increasing, the O-GlcNAc modified levels of total protein and the expression of OGT were up regulated (P<0.05, n=6) ; Alloxan could slow down the proliferation capacity, induce apoptosis[ (15.190±2.539) % vs (21.910±4.105) %, P=0.007], arrest cell cycle[G1 phase: (43.534±4.453) % vs (57.322±6.091) %, P=0.003; S phase: (50.747±5.937) % vs (37.201±4.661) %, P=0.001]. 28395449 6 54 theme protein 1001:1007 arg1 expression 1017:1026 the expression 1013:1026 the expression of OGT 1013:1033 Results: With the concentration of Vp16 increasing, the O-GlcNAc modified levels of total protein and the expression of OGT were up regulated (P<0.05, n=6) ; Alloxan could slow down the proliferation capacity, induce apoptosis[ (15.190±2.539) % vs (21.910±4.105) %, P=0.007], arrest cell cycle[G1 phase: (43.534±4.453) % vs (57.322±6.091) %, P=0.003; S phase: (50.747±5.937) % vs (37.201±4.661) %, P=0.001]. 28395449 4 55 theme Western 652:658 arg1 blot 660:663 Western blot 652:663 Western blot 652:663 Nalm-6 cells were treated with different concentrations of Vp16 for 12 h, and then the O-GlcNAc level and the expressions of OGT were examined by Western blot. 28395449 6 56 dep P=0.007 1177:1183 arg1 % 1306:1306 (37.201±4.661) % 1291:1306 (37.201±4.661) % 1291:1306 Results: With the concentration of Vp16 increasing, the O-GlcNAc modified levels of total protein and the expression of OGT were up regulated (P<0.05, n=6) ; Alloxan could slow down the proliferation capacity, induce apoptosis[ (15.190±2.539) % vs (21.910±4.105) %, P=0.007], arrest cell cycle[G1 phase: (43.534±4.453) % vs (57.322±6.091) %, P=0.003; S phase: (50.747±5.937) % vs (37.201±4.661) %, P=0.001]. 28395449 6 56 dep P=0.007 1177:1183 arg1 P=0.003 1253:1259 P=0.003 1253:1259 P=0.003; S phase 1253:1268 Results: With the concentration of Vp16 increasing, the O-GlcNAc modified levels of total protein and the expression of OGT were up regulated (P<0.05, n=6) ; Alloxan could slow down the proliferation capacity, induce apoptosis[ (15.190±2.539) % vs (21.910±4.105) %, P=0.007], arrest cell cycle[G1 phase: (43.534±4.453) % vs (57.322±6.091) %, P=0.003; S phase: (50.747±5.937) % vs (37.201±4.661) %, P=0.001]. 28395449 6 56 dep P=0.007 1177:1183 arg1 phase 1208:1212 arrest cell cycle[G1 phase 1187:1212 arrest cell cycle[G1 phase 1187:1212 Results: With the concentration of Vp16 increasing, the O-GlcNAc modified levels of total protein and the expression of OGT were up regulated (P<0.05, n=6) ; Alloxan could slow down the proliferation capacity, induce apoptosis[ (15.190±2.539) % vs (21.910±4.105) %, P=0.007], arrest cell cycle[G1 phase: (43.534±4.453) % vs (57.322±6.091) %, P=0.003; S phase: (50.747±5.937) % vs (37.201±4.661) %, P=0.001]. 28395449 6 56 dep P=0.007 1177:1183 arg1 P=0.001 1309:1315 P=0.001 1309:1315 P=0.001 1309:1315 Results: With the concentration of Vp16 increasing, the O-GlcNAc modified levels of total protein and the expression of OGT were up regulated (P<0.05, n=6) ; Alloxan could slow down the proliferation capacity, induce apoptosis[ (15.190±2.539) % vs (21.910±4.105) %, P=0.007], arrest cell cycle[G1 phase: (43.534±4.453) % vs (57.322±6.091) %, P=0.003; S phase: (50.747±5.937) % vs (37.201±4.661) %, P=0.001]. 28395449 6 56 dep P=0.007 1177:1183 arg1 % 1286:1286 (50.747±5.937) % 1271:1286 (50.747±5.937) % 1271:1286 Results: With the concentration of Vp16 increasing, the O-GlcNAc modified levels of total protein and the expression of OGT were up regulated (P<0.05, n=6) ; Alloxan could slow down the proliferation capacity, induce apoptosis[ (15.190±2.539) % vs (21.910±4.105) %, P=0.007], arrest cell cycle[G1 phase: (43.534±4.453) % vs (57.322±6.091) %, P=0.003; S phase: (50.747±5.937) % vs (37.201±4.661) %, P=0.001]. 28395449 6 56 dep P=0.007 1177:1183 arg1 % 1250:1250 (57.322±6.091) % 1235:1250 (57.322±6.091) % 1235:1250 Results: With the concentration of Vp16 increasing, the O-GlcNAc modified levels of total protein and the expression of OGT were up regulated (P<0.05, n=6) ; Alloxan could slow down the proliferation capacity, induce apoptosis[ (15.190±2.539) % vs (21.910±4.105) %, P=0.007], arrest cell cycle[G1 phase: (43.534±4.453) % vs (57.322±6.091) %, P=0.003; S phase: (50.747±5.937) % vs (37.201±4.661) %, P=0.001]. 28395449 6 56 dep P=0.007 1177:1183 arg1 % 1230:1230 (43.534±4.453) % 1215:1230 (43.534±4.453) % 1215:1230 Results: With the concentration of Vp16 increasing, the O-GlcNAc modified levels of total protein and the expression of OGT were up regulated (P<0.05, n=6) ; Alloxan could slow down the proliferation capacity, induce apoptosis[ (15.190±2.539) % vs (21.910±4.105) %, P=0.007], arrest cell cycle[G1 phase: (43.534±4.453) % vs (57.322±6.091) %, P=0.003; S phase: (50.747±5.937) % vs (37.201±4.661) %, P=0.001]. 28395449 4 57 theme Nalm-6 506:511 arg1 cells 513:517 Nalm-6 cells 506:517 Nalm-6 cells 506:517 Nalm-6 cells were treated with different concentrations of Vp16 for 12 h, and then the O-GlcNAc level and the expressions of OGT were examined by Western blot. 28395449 7 58 theme Vp16[ 1365:1369 arg1 % 1387:1387 Vp16[ (75.195±13.845) % 1365:1387 Vp16[ (75.195±13.845) % 1365:1387 Alloxan could inhibit the apoptosis caused by Vp16[ (75.195±13.845) % vs (52.741±10.815) %, P=0.011]along with Bax decreasing (5.496±1.998 vs 2.950±0.703, P=0.015) and Bcl-2 increasing (0.454±0.125 vs 0.803±0.223, P=0.013) . 28395449 8 59 theme biological 1660:1669 arg1 behaviors 1671:1679 the biological behaviors 1656:1679 the biological behaviors 1656:1679 Conclusion: Changes of O-GlcNAc modified level of Nalm-6 cells along with the inhibition of OGT could influence the biological behaviors and inhibit apoptosis induced by Vp16. 28395449 7 60 dep Bax 1430:1432 arg1 2.950±0.703 1461:1471 2.950±0.703 1461:1471 2.950±0.703 1461:1471 Alloxan could inhibit the apoptosis caused by Vp16[ (75.195±13.845) % vs (52.741±10.815) %, P=0.011]along with Bax decreasing (5.496±1.998 vs 2.950±0.703, P=0.015) and Bcl-2 increasing (0.454±0.125 vs 0.803±0.223, P=0.013) . 28395449 7 60 dep Bax 1430:1432 arg1 5.496±1.998 1446:1456 5.496±1.998 1446:1456 5.496±1.998 1446:1456 Alloxan could inhibit the apoptosis caused by Vp16[ (75.195±13.845) % vs (52.741±10.815) %, P=0.011]along with Bax decreasing (5.496±1.998 vs 2.950±0.703, P=0.015) and Bcl-2 increasing (0.454±0.125 vs 0.803±0.223, P=0.013) . 28395449 7 60 dep Bax 1430:1432 arg1 P=0.015 1474:1480 P=0.015 1474:1480 P=0.015 1474:1480 Alloxan could inhibit the apoptosis caused by Vp16[ (75.195±13.845) % vs (52.741±10.815) %, P=0.011]along with Bax decreasing (5.496±1.998 vs 2.950±0.703, P=0.015) and Bcl-2 increasing (0.454±0.125 vs 0.803±0.223, P=0.013) . 28395449 3 61 theme CCK-8 449:453 arg1 assay 455:459 CCK-8 assay 449:459 CCK-8 assay 449:459 The influence of Alloxan on Nalm-6 cells proliferation was checked by CCK-8 assay, apoptosis and cell cycle by flow cytometry. 28395449 7 62 dep % 1408:1408 arg1 P=0.011 1411:1417 P=0.011 1411:1417 P=0.011 1411:1417 Alloxan could inhibit the apoptosis caused by Vp16[ (75.195±13.845) % vs (52.741±10.815) %, P=0.011]along with Bax decreasing (5.496±1.998 vs 2.950±0.703, P=0.015) and Bcl-2 increasing (0.454±0.125 vs 0.803±0.223, P=0.013) . 28395449 1 63 gly glycosylation 156:168 arg1 cells 271:275 Nalm-6 cells 264:275 Nalm-6 cells 264:275 Objective: To explore the effects of O-GlcNAc glycosylation and its key enzyme OGT on the biological behaviors and etoposide (Vp16) -induced apoptosis of Nalm-6 cells. 28395449 5 64 theme Western 897:903 arg1 blot 905:908 Western blot 897:908 Western blot 897:908 After treating Nalm-6 with Alloxan for 24 h and then 5 μg/ml of Vp16 for 12 h, the apoptosis of different groups were measured with flow cytometry, and the expression of apoptosis-associated proteins Bax and Bcl-2 were examined by Western blot. 28395449 2 65 theme Nalm-6 309:314 arg1 model 322:326 Low O-GlcNAc modified Nalm-6 cells model 287:326 Low O-GlcNAc modified Nalm-6 cells model 287:326 Methods: Low O-GlcNAc modified Nalm-6 cells model was established with Alloxan, an inhibitor of OGT. 28395449 2 66 theme cells 316:320 arg1 model 322:326 Low O-GlcNAc modified Nalm-6 cells model 287:326 Low O-GlcNAc modified Nalm-6 cells model 287:326 Methods: Low O-GlcNAc modified Nalm-6 cells model was established with Alloxan, an inhibitor of OGT. 28395449 6 67 dep slow 1083:1086 arg1 induce 1121:1126 induce 1121:1126 induce apoptosis[ (15.190±2.539) % vs (21.910±4.105) %, P=0.007], arrest cell cycle[G1 phase: (43.534±4.453) % vs (57.322±6.091) %, P=0.003; S phase: (50.747±5.937) % vs (37.201±4.661) %, P=0.001] 1121:1316 Results: With the concentration of Vp16 increasing, the O-GlcNAc modified levels of total protein and the expression of OGT were up regulated (P<0.05, n=6) ; Alloxan could slow down the proliferation capacity, induce apoptosis[ (15.190±2.539) % vs (21.910±4.105) %, P=0.007], arrest cell cycle[G1 phase: (43.534±4.453) % vs (57.322±6.091) %, P=0.003; S phase: (50.747±5.937) % vs (37.201±4.661) %, P=0.001]. 28395449 6 68 theme total 995:999 arg1 protein 1001:1007 total protein 995:1007 total protein 995:1007 Results: With the concentration of Vp16 increasing, the O-GlcNAc modified levels of total protein and the expression of OGT were up regulated (P<0.05, n=6) ; Alloxan could slow down the proliferation capacity, induce apoptosis[ (15.190±2.539) % vs (21.910±4.105) %, P=0.007], arrest cell cycle[G1 phase: (43.534±4.453) % vs (57.322±6.091) %, P=0.003; S phase: (50.747±5.937) % vs (37.201±4.661) %, P=0.001]. 28395449 4 69 theme OGT 631:633 arg1 level 602:606 then the O-GlcNAc level 584:606 then the O-GlcNAc level 584:606 Nalm-6 cells were treated with different concentrations of Vp16 for 12 h, and then the O-GlcNAc level and the expressions of OGT were examined by Western blot. 28395449 4 69 theme OGT 631:633 arg1 expressions 616:626 the expressions 612:626 the expressions of OGT 612:633 Nalm-6 cells were treated with different concentrations of Vp16 for 12 h, and then the O-GlcNAc level and the expressions of OGT were examined by Western blot. 28395449 3 70 theme cells 414:418 arg1 proliferation 420:432 Nalm-6 cells proliferation 407:432 Nalm-6 cells proliferation 407:432 The influence of Alloxan on Nalm-6 cells proliferation was checked by CCK-8 assay, apoptosis and cell cycle by flow cytometry. 28395449 8 71 theme OGT 1636:1638 arg1 inhibition 1622:1631 the inhibition 1618:1631 Changes of O-GlcNAc modified level of Nalm-6 cells along with the inhibition of OGT 1556:1638 Conclusion: Changes of O-GlcNAc modified level of Nalm-6 cells along with the inhibition of OGT could influence the biological behaviors and inhibit apoptosis induced by Vp16. 28395449 8 72 dep along 1607:1611 arg1 with 1613:1616 with 1613:1616 with 1613:1616 Conclusion: Changes of O-GlcNAc modified level of Nalm-6 cells along with the inhibition of OGT could influence the biological behaviors and inhibit apoptosis induced by Vp16. 28395449 6 73 dep regulated 1043:1051 arg1 P<0.05 1054:1059 P<0.05 1054:1059 P<0.05 1054:1059 Results: With the concentration of Vp16 increasing, the O-GlcNAc modified levels of total protein and the expression of OGT were up regulated (P<0.05, n=6) ; Alloxan could slow down the proliferation capacity, induce apoptosis[ (15.190±2.539) % vs (21.910±4.105) %, P=0.007], arrest cell cycle[G1 phase: (43.534±4.453) % vs (57.322±6.091) %, P=0.003; S phase: (50.747±5.937) % vs (37.201±4.661) %, P=0.001]. 28395449 6 73 dep regulated 1043:1051 arg1 n=6 1062:1064 n=6 1062:1064 n=6 1062:1064 Results: With the concentration of Vp16 increasing, the O-GlcNAc modified levels of total protein and the expression of OGT were up regulated (P<0.05, n=6) ; Alloxan could slow down the proliferation capacity, induce apoptosis[ (15.190±2.539) % vs (21.910±4.105) %, P=0.007], arrest cell cycle[G1 phase: (43.534±4.453) % vs (57.322±6.091) %, P=0.003; S phase: (50.747±5.937) % vs (37.201±4.661) %, P=0.001]. 28395449 1 74 theme O-GlcNAc 147:154 arg1 glycosylation 156:168 O-GlcNAc glycosylation 147:168 O-GlcNAc glycosylation 147:168 Objective: To explore the effects of O-GlcNAc glycosylation and its key enzyme OGT on the biological behaviors and etoposide (Vp16) -induced apoptosis of Nalm-6 cells. 28160363 10 0 theme valuable 1369:1376 arg1 platform 1378:1385 a valuable platform 1367:1385 a valuable platform for producing potent biopharmaceutical products 1367:1433 The glyco-engineered BY2 lines provide a valuable platform for producing potent biopharmaceutical products. 28160363 1 1 gly glycoproteins 160:172 arg1 glycoproteins 160:172 Plant-produced glycoproteins 145:172 Plant-produced glycoproteins 145:172 Plant-produced glycoproteins contain N-linked glycans with plant-specific residues of β(1,2)-xylose and core α(1,3)-fucose, which do not exist in mammalian-derived proteins. 28160363 1 2 theme α 254:254 arg1 -fucose 260:266 core α(1,3)-fucose 249:266 core α(1,3)-fucose 249:266 Plant-produced glycoproteins contain N-linked glycans with plant-specific residues of β(1,2)-xylose and core α(1,3)-fucose, which do not exist in mammalian-derived proteins. 28160363 10 3 theme potent 1401:1406 arg1 products 1426:1433 potent biopharmaceutical products 1401:1433 potent biopharmaceutical products 1401:1433 The glyco-engineered BY2 lines provide a valuable platform for producing potent biopharmaceutical products. 28160363 11 4 theme multiplex 1519:1527 arg1 editing 1534:1540 multiplex gene editing 1519:1540 multiplex gene editing in BY2 cells 1519:1553 Furthermore, these results demonstrate the power of the CRISPR/Cas9 technology for multiplex gene editing in BY2 cells. 28160363 6 5 theme 1,3 1000:1002 arg1 -fucose 1004:1010 α(1,3)-fucose 998:1010 α(1,3)-fucose 998:1010 Glycan analysis of the endogenous proteins of these lines exhibited N-linked glycans lacking β(1,2)-xylose and/or α(1,3)-fucose. 28160363 8 6 theme expression 1102:1111 arg1 similar 1168:1174 similar 1168:1174 similar 1168:1174 The expression level and the activity of the recombinant protein were similar to that of the protein produced in the wild-type BY2 cells. 28160363 8 6 theme expression 1102:1111 arg1 level 1113:1117 The expression level 1098:1117 The expression level 1098:1117 The expression level and the activity of the recombinant protein were similar to that of the protein produced in the wild-type BY2 cells. 28160363 6 7 theme α 998:998 arg1 -fucose 1004:1010 α(1,3)-fucose 998:1010 α(1,3)-fucose 998:1010 Glycan analysis of the endogenous proteins of these lines exhibited N-linked glycans lacking β(1,2)-xylose and/or α(1,3)-fucose. 28160363 1 8 theme plant-specific 204:217 arg1 -fucose 260:266 core α(1,3)-fucose 249:266 core α(1,3)-fucose 249:266 Plant-produced glycoproteins contain N-linked glycans with plant-specific residues of β(1,2)-xylose and core α(1,3)-fucose, which do not exist in mammalian-derived proteins. 28160363 1 8 theme plant-specific 204:217 arg1 residues 219:226 plant-specific residues 204:226 plant-specific residues of β(1,2)-xylose and core α(1,3)-fucose, which do not exist in mammalian-derived proteins 204:316 Plant-produced glycoproteins contain N-linked glycans with plant-specific residues of β(1,2)-xylose and core α(1,3)-fucose, which do not exist in mammalian-derived proteins. 28160363 1 8 theme plant-specific 204:217 arg1 -xylose 237:243 β(1,2)-xylose 231:243 β(1,2)-xylose 231:243 Plant-produced glycoproteins contain N-linked glycans with plant-specific residues of β(1,2)-xylose and core α(1,3)-fucose, which do not exist in mammalian-derived proteins. 28160363 2 9 theme conscious 489:497 arg1 decision 499:506 a conscious decision to eliminate these moieties from plant-expressed proteins 487:564 a conscious decision to eliminate these moieties from plant-expressed proteins 487:564 Although our experience with two enzymes that are used for enzyme replacement therapy does not indicate that the plant sugar residues have deleterious effects, we made a conscious decision to eliminate these moieties from plant-expressed proteins. 28160363 2 10 used used 369:372 arg2 enzymes 352:358 two enzymes 348:358 two enzymes that are used for enzyme replacement therapy 348:403 Although our experience with two enzymes that are used for enzyme replacement therapy does not indicate that the plant sugar residues have deleterious effects, we made a conscious decision to eliminate these moieties from plant-expressed proteins. 28160363 11 11 theme CRISPR/Cas9 1492:1502 arg1 technology 1504:1513 the CRISPR/Cas9 technology 1488:1513 the CRISPR/Cas9 technology 1488:1513 Furthermore, these results demonstrate the power of the CRISPR/Cas9 technology for multiplex gene editing in BY2 cells. 28160363 3 12 theme CRISPR/Cas9 672:682 arg1 editing 691:697 CRISPR/Cas9 genome editing 672:697 CRISPR/Cas9 genome editing 672:697 We knocked out the β(1,2)-xylosyltranferase (XylT) and the α(1,3)-fucosyltransferase (FucT) genes, using CRISPR/Cas9 genome editing, in Nicotiana tabacum L. cv Bright Yellow 2 (BY2) cell suspension. 28160363 0 13 theme biotherapeutic 120:133 arg1 proteins 135:142 biotherapeutic proteins 120:142 biotherapeutic proteins 120:142 Establishment of a tobacco BY2 cell line devoid of plant-specific xylose and fucose as a platform for the production of biotherapeutic proteins. 28160363 8 14 theme protein 1155:1161 arg1 similar 1168:1174 similar 1168:1174 similar 1168:1174 The expression level and the activity of the recombinant protein were similar to that of the protein produced in the wild-type BY2 cells. 28160363 8 14 theme protein 1155:1161 arg1 level 1113:1117 The expression level 1098:1117 The expression level 1098:1117 The expression level and the activity of the recombinant protein were similar to that of the protein produced in the wild-type BY2 cells. 28160363 8 14 theme protein 1155:1161 arg1 activity 1127:1134 the activity 1123:1134 the activity of the recombinant protein 1123:1161 The expression level and the activity of the recombinant protein were similar to that of the protein produced in the wild-type BY2 cells. 28160363 3 15 theme tabacum 713:719 arg1 suspension 754:763 Nicotiana tabacum L. cv Bright Yellow 2 (BY2) cell suspension 703:763 Nicotiana tabacum L. cv Bright Yellow 2 (BY2) cell suspension 703:763 We knocked out the β(1,2)-xylosyltranferase (XylT) and the α(1,3)-fucosyltransferase (FucT) genes, using CRISPR/Cas9 genome editing, in Nicotiana tabacum L. cv Bright Yellow 2 (BY2) cell suspension. 28160363 3 16 theme β 586:586 arg1 XylT 612:615 XylT 612:615 XylT 612:615 We knocked out the β(1,2)-xylosyltranferase (XylT) and the α(1,3)-fucosyltransferase (FucT) genes, using CRISPR/Cas9 genome editing, in Nicotiana tabacum L. cv Bright Yellow 2 (BY2) cell suspension. 28160363 3 16 theme β 586:586 arg1 -xylosyltranferase 592:609 the β(1,2)-xylosyltranferase 582:609 the β(1,2)-xylosyltranferase (XylT) 582:616 We knocked out the β(1,2)-xylosyltranferase (XylT) and the α(1,3)-fucosyltransferase (FucT) genes, using CRISPR/Cas9 genome editing, in Nicotiana tabacum L. cv Bright Yellow 2 (BY2) cell suspension. 28160363 6 17 theme Glycan 884:889 arg1 analysis 891:898 Glycan analysis 884:898 Glycan analysis of the endogenous proteins of these lines 884:940 Glycan analysis of the endogenous proteins of these lines exhibited N-linked glycans lacking β(1,2)-xylose and/or α(1,3)-fucose. 28160363 2 18 theme deleterious 458:468 arg1 effects 470:476 deleterious effects 458:476 deleterious effects 458:476 Although our experience with two enzymes that are used for enzyme replacement therapy does not indicate that the plant sugar residues have deleterious effects, we made a conscious decision to eliminate these moieties from plant-expressed proteins. 28160363 7 19 theme recombinant 1078:1088 arg1 DNaseI 1090:1095 recombinant DNaseI 1078:1095 recombinant DNaseI 1078:1095 The knocked-out lines were further transformed successfully with recombinant DNaseI. 28160363 3 20 theme Yellow 734:739 arg1 suspension 754:763 Nicotiana tabacum L. cv Bright Yellow 2 (BY2) cell suspension 703:763 Nicotiana tabacum L. cv Bright Yellow 2 (BY2) cell suspension 703:763 We knocked out the β(1,2)-xylosyltranferase (XylT) and the α(1,3)-fucosyltransferase (FucT) genes, using CRISPR/Cas9 genome editing, in Nicotiana tabacum L. cv Bright Yellow 2 (BY2) cell suspension. 28160363 0 21 theme xylose 66:71 arg1 devoid 41:46 devoid 41:46 devoid 41:46 Establishment of a tobacco BY2 cell line devoid of plant-specific xylose and fucose as a platform for the production of biotherapeutic proteins. 28160363 1 22 theme mammalian-derived 291:307 arg1 proteins 309:316 mammalian-derived proteins 291:316 mammalian-derived proteins 291:316 Plant-produced glycoproteins contain N-linked glycans with plant-specific residues of β(1,2)-xylose and core α(1,3)-fucose, which do not exist in mammalian-derived proteins. 28160363 1 23 theme Plant-produced 145:158 arg1 glycoproteins 160:172 Plant-produced glycoproteins 145:172 Plant-produced glycoproteins 145:172 Plant-produced glycoproteins contain N-linked glycans with plant-specific residues of β(1,2)-xylose and core α(1,3)-fucose, which do not exist in mammalian-derived proteins. 28160363 3 24 theme cv 724:725 arg1 suspension 754:763 Nicotiana tabacum L. cv Bright Yellow 2 (BY2) cell suspension 703:763 Nicotiana tabacum L. cv Bright Yellow 2 (BY2) cell suspension 703:763 We knocked out the β(1,2)-xylosyltranferase (XylT) and the α(1,3)-fucosyltransferase (FucT) genes, using CRISPR/Cas9 genome editing, in Nicotiana tabacum L. cv Bright Yellow 2 (BY2) cell suspension. 28160363 0 25 theme fucose 77:82 arg1 devoid 41:46 devoid 41:46 devoid 41:46 Establishment of a tobacco BY2 cell line devoid of plant-specific xylose and fucose as a platform for the production of biotherapeutic proteins. 28160363 1 26 link N-linked 182:189 arg1 glycans 191:197 N-linked glycans 182:197 N-linked glycans 182:197 Plant-produced glycoproteins contain N-linked glycans with plant-specific residues of β(1,2)-xylose and core α(1,3)-fucose, which do not exist in mammalian-derived proteins. 28160363 6 27 theme lines 936:940 arg1 proteins 918:925 the endogenous proteins 903:925 the endogenous proteins of these lines 903:940 Glycan analysis of the endogenous proteins of these lines exhibited N-linked glycans lacking β(1,2)-xylose and/or α(1,3)-fucose. 28160363 3 28 dep -xylosyltranferase 592:609 arg1 genes 659:663 genes 659:663 genes 659:663 We knocked out the β(1,2)-xylosyltranferase (XylT) and the α(1,3)-fucosyltransferase (FucT) genes, using CRISPR/Cas9 genome editing, in Nicotiana tabacum L. cv Bright Yellow 2 (BY2) cell suspension. 28160363 11 29 from editing 1534:1540 arg1 cells 1549:1553 BY2 cells 1545:1553 BY2 cells 1545:1553 Furthermore, these results demonstrate the power of the CRISPR/Cas9 technology for multiplex gene editing in BY2 cells. 28160363 10 30 theme glyco-engineered 1332:1347 arg1 lines 1353:1357 The glyco-engineered BY2 lines 1328:1357 The glyco-engineered BY2 lines 1328:1357 The glyco-engineered BY2 lines provide a valuable platform for producing potent biopharmaceutical products. 28160363 8 31 theme BY2 1225:1227 arg1 cells 1229:1233 the wild-type BY2 cells 1211:1233 the wild-type BY2 cells 1211:1233 The expression level and the activity of the recombinant protein were similar to that of the protein produced in the wild-type BY2 cells. 28160363 2 32 theme enzyme 378:383 arg1 therapy 397:403 enzyme replacement therapy 378:403 enzyme replacement therapy 378:403 Although our experience with two enzymes that are used for enzyme replacement therapy does not indicate that the plant sugar residues have deleterious effects, we made a conscious decision to eliminate these moieties from plant-expressed proteins. 28160363 6 33 theme endogenous 907:916 arg1 proteins 918:925 the endogenous proteins 903:925 the endogenous proteins of these lines 903:940 Glycan analysis of the endogenous proteins of these lines exhibited N-linked glycans lacking β(1,2)-xylose and/or α(1,3)-fucose. 28160363 2 34 theme plant 432:436 arg1 residues 444:451 the plant sugar residues 428:451 the plant sugar residues 428:451 Although our experience with two enzymes that are used for enzyme replacement therapy does not indicate that the plant sugar residues have deleterious effects, we made a conscious decision to eliminate these moieties from plant-expressed proteins. 28160363 0 35 theme BY2 27:29 arg1 line 36:39 a tobacco BY2 cell line 17:39 a tobacco BY2 cell line devoid of plant-specific xylose and fucose as a platform for the production of biotherapeutic proteins 17:142 Establishment of a tobacco BY2 cell line devoid of plant-specific xylose and fucose as a platform for the production of biotherapeutic proteins. 28160363 3 36 theme 1,2 588:590 arg1 XylT 612:615 XylT 612:615 XylT 612:615 We knocked out the β(1,2)-xylosyltranferase (XylT) and the α(1,3)-fucosyltransferase (FucT) genes, using CRISPR/Cas9 genome editing, in Nicotiana tabacum L. cv Bright Yellow 2 (BY2) cell suspension. 28160363 3 36 theme 1,2 588:590 arg1 -xylosyltranferase 592:609 the β(1,2)-xylosyltranferase 582:609 the β(1,2)-xylosyltranferase (XylT) 582:616 We knocked out the β(1,2)-xylosyltranferase (XylT) and the α(1,3)-fucosyltransferase (FucT) genes, using CRISPR/Cas9 genome editing, in Nicotiana tabacum L. cv Bright Yellow 2 (BY2) cell suspension. 28160363 0 37 theme line 36:39 arg1 Establishment 0:12 Establishment 0:12 Establishment of a tobacco BY2 cell line devoid of plant-specific xylose and fucose as a platform for the production of biotherapeutic proteins. 0:143 Establishment of a tobacco BY2 cell line devoid of plant-specific xylose and fucose as a platform for the production of biotherapeutic proteins. 28160363 11 38 theme BY2 1545:1547 arg1 cells 1549:1553 BY2 cells 1545:1553 BY2 cells 1545:1553 Furthermore, these results demonstrate the power of the CRISPR/Cas9 technology for multiplex gene editing in BY2 cells. 28160363 6 39 link N-linked 952:959 arg1 glycans 961:967 N-linked glycans 952:967 N-linked glycans lacking β(1,2)-xylose and/or α(1,3)-fucose 952:1010 Glycan analysis of the endogenous proteins of these lines exhibited N-linked glycans lacking β(1,2)-xylose and/or α(1,3)-fucose. 28160363 1 40 theme β 231:231 arg1 -xylose 237:243 β(1,2)-xylose 231:243 β(1,2)-xylose 231:243 Plant-produced glycoproteins contain N-linked glycans with plant-specific residues of β(1,2)-xylose and core α(1,3)-fucose, which do not exist in mammalian-derived proteins. 28160363 5 41 theme typical 858:864 arg1 rate 878:881 a typical BY2 growing rate 856:881 a typical BY2 growing rate 856:881 The knocked-out lines were stable, viable and exhibited a typical BY2 growing rate. 28160363 1 42 theme 1,2 233:235 arg1 -xylose 237:243 β(1,2)-xylose 231:243 β(1,2)-xylose 231:243 Plant-produced glycoproteins contain N-linked glycans with plant-specific residues of β(1,2)-xylose and core α(1,3)-fucose, which do not exist in mammalian-derived proteins. 28160363 5 43 theme growing 870:876 arg1 rate 878:881 a typical BY2 growing rate 856:881 a typical BY2 growing rate 856:881 The knocked-out lines were stable, viable and exhibited a typical BY2 growing rate. 28160363 3 44 theme 1,3 628:630 arg1 -fucosyltransferase 632:650 the α(1,3)-fucosyltransferase 622:650 the α(1,3)-fucosyltransferase (FucT) 622:657 We knocked out the β(1,2)-xylosyltranferase (XylT) and the α(1,3)-fucosyltransferase (FucT) genes, using CRISPR/Cas9 genome editing, in Nicotiana tabacum L. cv Bright Yellow 2 (BY2) cell suspension. 28160363 3 44 theme 1,3 628:630 arg1 FucT 653:656 FucT 653:656 FucT 653:656 We knocked out the β(1,2)-xylosyltranferase (XylT) and the α(1,3)-fucosyltransferase (FucT) genes, using CRISPR/Cas9 genome editing, in Nicotiana tabacum L. cv Bright Yellow 2 (BY2) cell suspension. 28160363 1 45 theme -xylose 237:243 arg1 -fucose 260:266 core α(1,3)-fucose 249:266 core α(1,3)-fucose 249:266 Plant-produced glycoproteins contain N-linked glycans with plant-specific residues of β(1,2)-xylose and core α(1,3)-fucose, which do not exist in mammalian-derived proteins. 28160363 1 45 theme -xylose 237:243 arg1 residues 219:226 plant-specific residues 204:226 plant-specific residues of β(1,2)-xylose and core α(1,3)-fucose, which do not exist in mammalian-derived proteins 204:316 Plant-produced glycoproteins contain N-linked glycans with plant-specific residues of β(1,2)-xylose and core α(1,3)-fucose, which do not exist in mammalian-derived proteins. 28160363 1 45 theme -xylose 237:243 arg1 -xylose 237:243 β(1,2)-xylose 231:243 β(1,2)-xylose 231:243 Plant-produced glycoproteins contain N-linked glycans with plant-specific residues of β(1,2)-xylose and core α(1,3)-fucose, which do not exist in mammalian-derived proteins. 28160363 6 46 theme N-linked 952:959 arg1 glycans 961:967 N-linked glycans 952:967 N-linked glycans lacking β(1,2)-xylose and/or α(1,3)-fucose 952:1010 Glycan analysis of the endogenous proteins of these lines exhibited N-linked glycans lacking β(1,2)-xylose and/or α(1,3)-fucose. 28160363 3 47 theme α 626:626 arg1 -fucosyltransferase 632:650 the α(1,3)-fucosyltransferase 622:650 the α(1,3)-fucosyltransferase (FucT) 622:657 We knocked out the β(1,2)-xylosyltranferase (XylT) and the α(1,3)-fucosyltransferase (FucT) genes, using CRISPR/Cas9 genome editing, in Nicotiana tabacum L. cv Bright Yellow 2 (BY2) cell suspension. 28160363 3 47 theme α 626:626 arg1 FucT 653:656 FucT 653:656 FucT 653:656 We knocked out the β(1,2)-xylosyltranferase (XylT) and the α(1,3)-fucosyltransferase (FucT) genes, using CRISPR/Cas9 genome editing, in Nicotiana tabacum L. cv Bright Yellow 2 (BY2) cell suspension. 28160363 1 48 theme core 249:252 arg1 1,3 256:258 1,3 256:258 1,3 256:258 Plant-produced glycoproteins contain N-linked glycans with plant-specific residues of β(1,2)-xylose and core α(1,3)-fucose, which do not exist in mammalian-derived proteins. 28160363 1 48 theme core 249:252 arg1 α 254:254 core α 249:254 core α(1,3)-fucose 249:266 Plant-produced glycoproteins contain N-linked glycans with plant-specific residues of β(1,2)-xylose and core α(1,3)-fucose, which do not exist in mammalian-derived proteins. 28160363 2 49 theme plant-expressed 541:555 arg1 proteins 557:564 plant-expressed proteins 541:564 plant-expressed proteins 541:564 Although our experience with two enzymes that are used for enzyme replacement therapy does not indicate that the plant sugar residues have deleterious effects, we made a conscious decision to eliminate these moieties from plant-expressed proteins. 28160363 10 50 theme biopharmaceutical 1408:1424 arg1 products 1426:1433 potent biopharmaceutical products 1401:1433 potent biopharmaceutical products 1401:1433 The glyco-engineered BY2 lines provide a valuable platform for producing potent biopharmaceutical products. 28160363 11 51 theme gene 1529:1532 arg1 editing 1534:1540 multiplex gene editing 1519:1540 multiplex gene editing in BY2 cells 1519:1553 Furthermore, these results demonstrate the power of the CRISPR/Cas9 technology for multiplex gene editing in BY2 cells. 28160363 1 52 theme N-linked 182:189 arg1 glycans 191:197 N-linked glycans 182:197 N-linked glycans 182:197 Plant-produced glycoproteins contain N-linked glycans with plant-specific residues of β(1,2)-xylose and core α(1,3)-fucose, which do not exist in mammalian-derived proteins. 28160363 0 53 theme proteins 135:142 arg1 production 106:115 the production 102:115 the production of biotherapeutic proteins 102:142 Establishment of a tobacco BY2 cell line devoid of plant-specific xylose and fucose as a platform for the production of biotherapeutic proteins. 28160363 3 54 theme genome 684:689 arg1 editing 691:697 CRISPR/Cas9 genome editing 672:697 CRISPR/Cas9 genome editing 672:697 We knocked out the β(1,2)-xylosyltranferase (XylT) and the α(1,3)-fucosyltransferase (FucT) genes, using CRISPR/Cas9 genome editing, in Nicotiana tabacum L. cv Bright Yellow 2 (BY2) cell suspension. 28160363 3 55 theme cell 749:752 arg1 suspension 754:763 Nicotiana tabacum L. cv Bright Yellow 2 (BY2) cell suspension 703:763 Nicotiana tabacum L. cv Bright Yellow 2 (BY2) cell suspension 703:763 We knocked out the β(1,2)-xylosyltranferase (XylT) and the α(1,3)-fucosyltransferase (FucT) genes, using CRISPR/Cas9 genome editing, in Nicotiana tabacum L. cv Bright Yellow 2 (BY2) cell suspension. 28160363 8 56 theme recombinant 1143:1153 arg1 protein 1155:1161 the recombinant protein 1139:1161 the recombinant protein 1139:1161 The expression level and the activity of the recombinant protein were similar to that of the protein produced in the wild-type BY2 cells. 28160363 3 57 theme L. 721:722 arg1 suspension 754:763 Nicotiana tabacum L. cv Bright Yellow 2 (BY2) cell suspension 703:763 Nicotiana tabacum L. cv Bright Yellow 2 (BY2) cell suspension 703:763 We knocked out the β(1,2)-xylosyltranferase (XylT) and the α(1,3)-fucosyltransferase (FucT) genes, using CRISPR/Cas9 genome editing, in Nicotiana tabacum L. cv Bright Yellow 2 (BY2) cell suspension. 28160363 0 58 theme plant-specific 51:64 arg1 xylose 66:71 xylose 66:71 xylose 66:71 Establishment of a tobacco BY2 cell line devoid of plant-specific xylose and fucose as a platform for the production of biotherapeutic proteins. 28160363 3 59 theme BY2 744:746 arg1 suspension 754:763 Nicotiana tabacum L. cv Bright Yellow 2 (BY2) cell suspension 703:763 Nicotiana tabacum L. cv Bright Yellow 2 (BY2) cell suspension 703:763 We knocked out the β(1,2)-xylosyltranferase (XylT) and the α(1,3)-fucosyltransferase (FucT) genes, using CRISPR/Cas9 genome editing, in Nicotiana tabacum L. cv Bright Yellow 2 (BY2) cell suspension. 28160363 5 60 dep stable 827:832 arg1 viable 835:840 viable 835:840 viable 835:840 The knocked-out lines were stable, viable and exhibited a typical BY2 growing rate. 28160363 5 60 dep stable 827:832 arg1 stable 827:832 stable 827:832 stable 827:832 The knocked-out lines were stable, viable and exhibited a typical BY2 growing rate. 28160363 5 60 dep stable 827:832 arg1 lines 816:820 The knocked-out lines 800:820 The knocked-out lines 800:820 The knocked-out lines were stable, viable and exhibited a typical BY2 growing rate. 28160363 3 61 theme Nicotiana 703:711 arg1 suspension 754:763 Nicotiana tabacum L. cv Bright Yellow 2 (BY2) cell suspension 703:763 Nicotiana tabacum L. cv Bright Yellow 2 (BY2) cell suspension 703:763 We knocked out the β(1,2)-xylosyltranferase (XylT) and the α(1,3)-fucosyltransferase (FucT) genes, using CRISPR/Cas9 genome editing, in Nicotiana tabacum L. cv Bright Yellow 2 (BY2) cell suspension. 28160363 2 62 theme sugar 438:442 arg1 residues 444:451 the plant sugar residues 428:451 the plant sugar residues 428:451 Although our experience with two enzymes that are used for enzyme replacement therapy does not indicate that the plant sugar residues have deleterious effects, we made a conscious decision to eliminate these moieties from plant-expressed proteins. 28160363 3 63 theme Bright 727:732 arg1 suspension 754:763 Nicotiana tabacum L. cv Bright Yellow 2 (BY2) cell suspension 703:763 Nicotiana tabacum L. cv Bright Yellow 2 (BY2) cell suspension 703:763 We knocked out the β(1,2)-xylosyltranferase (XylT) and the α(1,3)-fucosyltransferase (FucT) genes, using CRISPR/Cas9 genome editing, in Nicotiana tabacum L. cv Bright Yellow 2 (BY2) cell suspension. 28160363 7 64 theme knocked-out 1017:1027 arg1 lines 1029:1033 The knocked-out lines 1013:1033 The knocked-out lines 1013:1033 The knocked-out lines were further transformed successfully with recombinant DNaseI. 28160363 2 65 dep our 328:330 arg1 experience 332:341 experience 332:341 experience 332:341 Although our experience with two enzymes that are used for enzyme replacement therapy does not indicate that the plant sugar residues have deleterious effects, we made a conscious decision to eliminate these moieties from plant-expressed proteins. 28160363 5 66 theme knocked-out 804:814 arg1 viable 835:840 viable 835:840 viable 835:840 The knocked-out lines were stable, viable and exhibited a typical BY2 growing rate. 28160363 5 66 theme knocked-out 804:814 arg1 stable 827:832 stable 827:832 stable 827:832 The knocked-out lines were stable, viable and exhibited a typical BY2 growing rate. 28160363 5 66 theme knocked-out 804:814 arg1 lines 816:820 The knocked-out lines 800:820 The knocked-out lines 800:820 The knocked-out lines were stable, viable and exhibited a typical BY2 growing rate. 28160363 1 67 link mammalian-derived 291:307 arg1 proteins 309:316 mammalian-derived proteins 291:316 mammalian-derived proteins 291:316 Plant-produced glycoproteins contain N-linked glycans with plant-specific residues of β(1,2)-xylose and core α(1,3)-fucose, which do not exist in mammalian-derived proteins. 28160363 0 68 theme tobacco 19:25 arg1 line 36:39 a tobacco BY2 cell line 17:39 a tobacco BY2 cell line devoid of plant-specific xylose and fucose as a platform for the production of biotherapeutic proteins 17:142 Establishment of a tobacco BY2 cell line devoid of plant-specific xylose and fucose as a platform for the production of biotherapeutic proteins. 28160363 6 69 theme proteins 918:925 arg1 analysis 891:898 Glycan analysis 884:898 Glycan analysis of the endogenous proteins of these lines 884:940 Glycan analysis of the endogenous proteins of these lines exhibited N-linked glycans lacking β(1,2)-xylose and/or α(1,3)-fucose. 28160363 2 70 theme replacement 385:395 arg1 therapy 397:403 enzyme replacement therapy 378:403 enzyme replacement therapy 378:403 Although our experience with two enzymes that are used for enzyme replacement therapy does not indicate that the plant sugar residues have deleterious effects, we made a conscious decision to eliminate these moieties from plant-expressed proteins. 28160363 8 71 theme wild-type 1215:1223 arg1 cells 1229:1233 the wild-type BY2 cells 1211:1233 the wild-type BY2 cells 1211:1233 The expression level and the activity of the recombinant protein were similar to that of the protein produced in the wild-type BY2 cells. 28160363 0 72 theme cell 31:34 arg1 line 36:39 a tobacco BY2 cell line 17:39 a tobacco BY2 cell line devoid of plant-specific xylose and fucose as a platform for the production of biotherapeutic proteins 17:142 Establishment of a tobacco BY2 cell line devoid of plant-specific xylose and fucose as a platform for the production of biotherapeutic proteins. 28160363 1 73 theme -fucose 260:266 arg1 -fucose 260:266 core α(1,3)-fucose 249:266 core α(1,3)-fucose 249:266 Plant-produced glycoproteins contain N-linked glycans with plant-specific residues of β(1,2)-xylose and core α(1,3)-fucose, which do not exist in mammalian-derived proteins. 28160363 1 73 theme -fucose 260:266 arg1 residues 219:226 plant-specific residues 204:226 plant-specific residues of β(1,2)-xylose and core α(1,3)-fucose, which do not exist in mammalian-derived proteins 204:316 Plant-produced glycoproteins contain N-linked glycans with plant-specific residues of β(1,2)-xylose and core α(1,3)-fucose, which do not exist in mammalian-derived proteins. 28160363 1 73 theme -fucose 260:266 arg1 -xylose 237:243 β(1,2)-xylose 231:243 β(1,2)-xylose 231:243 Plant-produced glycoproteins contain N-linked glycans with plant-specific residues of β(1,2)-xylose and core α(1,3)-fucose, which do not exist in mammalian-derived proteins. 28160363 1 74 contain contain 174:180 arg1 glycoproteins 160:172 Plant-produced glycoproteins 145:172 Plant-produced glycoproteins 145:172 Plant-produced glycoproteins contain N-linked glycans with plant-specific residues of β(1,2)-xylose and core α(1,3)-fucose, which do not exist in mammalian-derived proteins. 28160363 1 74 contain contain 174:180 arg2 glycans 191:197 N-linked glycans 182:197 N-linked glycans 182:197 Plant-produced glycoproteins contain N-linked glycans with plant-specific residues of β(1,2)-xylose and core α(1,3)-fucose, which do not exist in mammalian-derived proteins. 28160363 0 75 theme devoid 41:46 arg1 line 36:39 a tobacco BY2 cell line 17:39 a tobacco BY2 cell line devoid of plant-specific xylose and fucose as a platform for the production of biotherapeutic proteins 17:142 Establishment of a tobacco BY2 cell line devoid of plant-specific xylose and fucose as a platform for the production of biotherapeutic proteins. 28160363 9 76 from fucose 1311:1316 arg1 free 1283:1286 free 1283:1286 free 1283:1286 The recombinant DNaseI was shown to be totally free from any xylose and/or fucose residues. 28160363 9 76 from fucose 1311:1316 arg1 DNaseI 1252:1257 The recombinant DNaseI 1236:1257 The recombinant DNaseI 1236:1257 The recombinant DNaseI was shown to be totally free from any xylose and/or fucose residues. 28160363 2 77 contain have 453:456 arg1 residues 444:451 the plant sugar residues 428:451 the plant sugar residues 428:451 Although our experience with two enzymes that are used for enzyme replacement therapy does not indicate that the plant sugar residues have deleterious effects, we made a conscious decision to eliminate these moieties from plant-expressed proteins. 28160363 2 77 contain have 453:456 arg2 effects 470:476 deleterious effects 458:476 deleterious effects 458:476 Although our experience with two enzymes that are used for enzyme replacement therapy does not indicate that the plant sugar residues have deleterious effects, we made a conscious decision to eliminate these moieties from plant-expressed proteins. 28160363 9 78 from xylose 1297:1302 arg1 free 1283:1286 free 1283:1286 free 1283:1286 The recombinant DNaseI was shown to be totally free from any xylose and/or fucose residues. 28160363 9 78 from xylose 1297:1302 arg1 DNaseI 1252:1257 The recombinant DNaseI 1236:1257 The recombinant DNaseI 1236:1257 The recombinant DNaseI was shown to be totally free from any xylose and/or fucose residues. 28160363 6 79 theme 1,2 979:981 arg1 -xylose 983:989 β(1,2)-xylose 977:989 β(1,2)-xylose 977:989 Glycan analysis of the endogenous proteins of these lines exhibited N-linked glycans lacking β(1,2)-xylose and/or α(1,3)-fucose. 28160363 10 80 theme BY2 1349:1351 arg1 lines 1353:1357 The glyco-engineered BY2 lines 1328:1357 The glyco-engineered BY2 lines 1328:1357 The glyco-engineered BY2 lines provide a valuable platform for producing potent biopharmaceutical products. 28160363 5 81 theme BY2 866:868 arg1 rate 878:881 a typical BY2 growing rate 856:881 a typical BY2 growing rate 856:881 The knocked-out lines were stable, viable and exhibited a typical BY2 growing rate. 28160363 6 82 theme β 977:977 arg1 -xylose 983:989 β(1,2)-xylose 977:989 β(1,2)-xylose 977:989 Glycan analysis of the endogenous proteins of these lines exhibited N-linked glycans lacking β(1,2)-xylose and/or α(1,3)-fucose. 28160363 11 83 theme technology 1504:1513 arg1 power 1479:1483 the power 1475:1483 the power of the CRISPR/Cas9 technology for multiplex gene editing in BY2 cells 1475:1553 Furthermore, these results demonstrate the power of the CRISPR/Cas9 technology for multiplex gene editing in BY2 cells. 28160363 9 84 dep xylose 1297:1302 arg1 residues 1318:1325 residues 1318:1325 residues 1318:1325 The recombinant DNaseI was shown to be totally free from any xylose and/or fucose residues. 28160363 9 84 dep xylose 1297:1302 arg1 any 1293:1295 any 1293:1295 any 1293:1295 The recombinant DNaseI was shown to be totally free from any xylose and/or fucose residues. 28160363 9 85 theme recombinant 1240:1250 arg1 free 1283:1286 free 1283:1286 free 1283:1286 The recombinant DNaseI was shown to be totally free from any xylose and/or fucose residues. 28160363 9 85 theme recombinant 1240:1250 arg1 DNaseI 1252:1257 The recombinant DNaseI 1236:1257 The recombinant DNaseI 1236:1257 The recombinant DNaseI was shown to be totally free from any xylose and/or fucose residues. 26899450 5 0 theme PNGase 787:792 arg1 F 794:794 immobilized recombinant glutathione-S-transferase (GST) tagged PNGase F 724:794 immobilized recombinant glutathione-S-transferase (GST) tagged PNGase F enzyme microcolumns for rapid and efficient removal of N-linked carbohydrates from glycoproteins 724:891 In this paper, we report on the design and implementation of immobilized recombinant glutathione-S-transferase (GST) tagged PNGase F enzyme microcolumns for rapid and efficient removal of N-linked carbohydrates from glycoproteins. 26899450 6 1 theme based 967:971 arg1 protocols 973:981 conventional in-solution based protocols 942:981 conventional in-solution based protocols 942:981 Digestion speed and efficiency were compared to conventional in-solution based protocols. 26899450 7 2 from removal 1063:1069 arg1 10min 1074:1078 10min 1074:1078 10min 1074:1078 The use of PNGase F functionalized microcolumns resulted in efficient N-glycan removal in 10min from all major N-linked glycoprotein types of: (i) neutral (IgG), (ii) highly sialylated (fetuin), and (iii) high mannose (ribonuclease B) carbohydrate containing glycoprotein standards. 26899450 7 3 gly glycoprotein 1243:1254 arg1 glycoprotein 1243:1254 glycoprotein standards 1243:1264 glycoprotein standards 1243:1264 The use of PNGase F functionalized microcolumns resulted in efficient N-glycan removal in 10min from all major N-linked glycoprotein types of: (i) neutral (IgG), (ii) highly sialylated (fetuin), and (iii) high mannose (ribonuclease B) carbohydrate containing glycoprotein standards. 26899450 3 4 theme biomedical 520:529 arg1 field 531:535 the biomedical field 516:535 the biomedical field 516:535 On the other hand, identification of disease related glycosylation alterations can serve as early indicators (glycobiomarkers) for various pathological conditions in the biomedical field. 26899450 5 5 from removal 840:846 arg1 glycoproteins 879:891 glycoproteins 879:891 glycoproteins 879:891 In this paper, we report on the design and implementation of immobilized recombinant glutathione-S-transferase (GST) tagged PNGase F enzyme microcolumns for rapid and efficient removal of N-linked carbohydrates from glycoproteins. 26899450 4 6 theme easy 589:592 arg1 methods 625:631 rapid and easy to automate sample preparation methods 579:631 rapid and easy to automate sample preparation methods 579:631 Therefore, there is a growing demand for rapid and easy to automate sample preparation methods for N-glycosylation analysis. 26899450 5 7 theme F 794:794 arg1 microcolumns 803:814 immobilized recombinant glutathione-S-transferase (GST) tagged PNGase F enzyme microcolumns 724:814 immobilized recombinant glutathione-S-transferase (GST) tagged PNGase F enzyme microcolumns for rapid and efficient removal of N-linked carbohydrates from glycoproteins 724:891 In this paper, we report on the design and implementation of immobilized recombinant glutathione-S-transferase (GST) tagged PNGase F enzyme microcolumns for rapid and efficient removal of N-linked carbohydrates from glycoproteins. 26899450 6 8 theme in-solution 955:965 arg1 protocols 973:981 conventional in-solution based protocols 942:981 conventional in-solution based protocols 942:981 Digestion speed and efficiency were compared to conventional in-solution based protocols. 26899450 1 9 from phase 170:174 arg1 industry 224:231 the biopharmaceutical industry 202:231 the biopharmaceutical industry 202:231 N-glycosylation profiling of glycoprotein biotherapeutics is an essential step in each phase of product development in the biopharmaceutical industry. 26899450 8 10 theme automated 1306:1314 arg1 systems 1335:1341 automated sample preparation systems 1306:1341 automated sample preparation systems 1306:1341 The approach can be readily applied to automated sample preparation systems, such as liquid handling robots. 26899450 8 10 theme automated 1306:1314 arg1 robots 1368:1373 liquid handling robots 1352:1373 liquid handling robots 1352:1373 The approach can be readily applied to automated sample preparation systems, such as liquid handling robots. 26899450 8 11 theme handling 1359:1366 arg1 robots 1368:1373 liquid handling robots 1352:1373 liquid handling robots 1352:1373 The approach can be readily applied to automated sample preparation systems, such as liquid handling robots. 26899450 5 12 theme recombinant 736:746 arg1 GST 775:777 GST 775:777 GST 775:777 In this paper, we report on the design and implementation of immobilized recombinant glutathione-S-transferase (GST) tagged PNGase F enzyme microcolumns for rapid and efficient removal of N-linked carbohydrates from glycoproteins. 26899450 5 12 theme recombinant 736:746 arg1 glutathione-S-transferase 748:772 recombinant glutathione-S-transferase 736:772 immobilized recombinant glutathione-S-transferase (GST) tagged PNGase F enzyme microcolumns for rapid and efficient removal of N-linked carbohydrates from glycoproteins 724:891 In this paper, we report on the design and implementation of immobilized recombinant glutathione-S-transferase (GST) tagged PNGase F enzyme microcolumns for rapid and efficient removal of N-linked carbohydrates from glycoproteins. 26899450 3 13 from conditions 502:511 arg1 field 531:535 the biomedical field 516:535 the biomedical field 516:535 On the other hand, identification of disease related glycosylation alterations can serve as early indicators (glycobiomarkers) for various pathological conditions in the biomedical field. 26899450 5 14 link N-linked 851:858 arg1 carbohydrates 860:872 N-linked carbohydrates 851:872 N-linked carbohydrates from glycoproteins 851:891 In this paper, we report on the design and implementation of immobilized recombinant glutathione-S-transferase (GST) tagged PNGase F enzyme microcolumns for rapid and efficient removal of N-linked carbohydrates from glycoproteins. 26899450 3 15 theme related 395:401 arg1 alterations 417:427 disease related glycosylation alterations 387:427 disease related glycosylation alterations 387:427 On the other hand, identification of disease related glycosylation alterations can serve as early indicators (glycobiomarkers) for various pathological conditions in the biomedical field. 26899450 7 16 theme high 1189:1192 arg1 carbohydrate 1219:1230 high mannose (ribonuclease B) carbohydrate 1189:1230 high mannose (ribonuclease B) carbohydrate 1189:1230 The use of PNGase F functionalized microcolumns resulted in efficient N-glycan removal in 10min from all major N-linked glycoprotein types of: (i) neutral (IgG), (ii) highly sialylated (fetuin), and (iii) high mannose (ribonuclease B) carbohydrate containing glycoprotein standards. 26899450 7 17 dep containing 1232:1241 arg1 iii 1184:1186 iii 1184:1186 iii 1184:1186 The use of PNGase F functionalized microcolumns resulted in efficient N-glycan removal in 10min from all major N-linked glycoprotein types of: (i) neutral (IgG), (ii) highly sialylated (fetuin), and (iii) high mannose (ribonuclease B) carbohydrate containing glycoprotein standards. 26899450 3 18 theme glycosylation 403:415 arg1 alterations 417:427 disease related glycosylation alterations 387:427 disease related glycosylation alterations 387:427 On the other hand, identification of disease related glycosylation alterations can serve as early indicators (glycobiomarkers) for various pathological conditions in the biomedical field. 26899450 5 19 theme glutathione-S-transferase 748:772 arg1 F 794:794 immobilized recombinant glutathione-S-transferase (GST) tagged PNGase F 724:794 immobilized recombinant glutathione-S-transferase (GST) tagged PNGase F enzyme microcolumns for rapid and efficient removal of N-linked carbohydrates from glycoproteins 724:891 In this paper, we report on the design and implementation of immobilized recombinant glutathione-S-transferase (GST) tagged PNGase F enzyme microcolumns for rapid and efficient removal of N-linked carbohydrates from glycoproteins. 26899450 5 20 theme efficient 830:838 arg1 removal 840:846 rapid and efficient removal 820:846 rapid and efficient removal of N-linked carbohydrates from glycoproteins 820:891 In this paper, we report on the design and implementation of immobilized recombinant glutathione-S-transferase (GST) tagged PNGase F enzyme microcolumns for rapid and efficient removal of N-linked carbohydrates from glycoproteins. 26899450 7 21 theme mannose 1194:1200 arg1 carbohydrate 1219:1230 high mannose (ribonuclease B) carbohydrate 1189:1230 high mannose (ribonuclease B) carbohydrate 1189:1230 The use of PNGase F functionalized microcolumns resulted in efficient N-glycan removal in 10min from all major N-linked glycoprotein types of: (i) neutral (IgG), (ii) highly sialylated (fetuin), and (iii) high mannose (ribonuclease B) carbohydrate containing glycoprotein standards. 26899450 7 22 theme PNGase 995:1000 arg1 F 1002:1002 PNGase F 995:1002 PNGase F functionalized microcolumns 995:1030 The use of PNGase F functionalized microcolumns resulted in efficient N-glycan removal in 10min from all major N-linked glycoprotein types of: (i) neutral (IgG), (ii) highly sialylated (fetuin), and (iii) high mannose (ribonuclease B) carbohydrate containing glycoprotein standards. 26899450 7 23 theme B 1216:1216 arg1 carbohydrate 1219:1230 high mannose (ribonuclease B) carbohydrate 1189:1230 high mannose (ribonuclease B) carbohydrate 1189:1230 The use of PNGase F functionalized microcolumns resulted in efficient N-glycan removal in 10min from all major N-linked glycoprotein types of: (i) neutral (IgG), (ii) highly sialylated (fetuin), and (iii) high mannose (ribonuclease B) carbohydrate containing glycoprotein standards. 26899450 5 24 theme carbohydrates 860:872 arg1 removal 840:846 rapid and efficient removal 820:846 rapid and efficient removal of N-linked carbohydrates from glycoproteins 820:891 In this paper, we report on the design and implementation of immobilized recombinant glutathione-S-transferase (GST) tagged PNGase F enzyme microcolumns for rapid and efficient removal of N-linked carbohydrates from glycoproteins. 26899450 4 25 theme N-glycosylation 637:651 arg1 analysis 653:660 N-glycosylation analysis 637:660 N-glycosylation analysis 637:660 Therefore, there is a growing demand for rapid and easy to automate sample preparation methods for N-glycosylation analysis. 26899450 8 26 theme preparation 1323:1333 arg1 systems 1335:1341 automated sample preparation systems 1306:1341 automated sample preparation systems 1306:1341 The approach can be readily applied to automated sample preparation systems, such as liquid handling robots. 26899450 8 26 theme preparation 1323:1333 arg1 robots 1368:1373 liquid handling robots 1352:1373 liquid handling robots 1352:1373 The approach can be readily applied to automated sample preparation systems, such as liquid handling robots. 26899450 1 27 theme product 179:185 arg1 development 187:197 product development 179:197 product development 179:197 N-glycosylation profiling of glycoprotein biotherapeutics is an essential step in each phase of product development in the biopharmaceutical industry. 26899450 1 28 gly glycoprotein 112:123 arg1 glycoprotein 112:123 glycoprotein biotherapeutics 112:139 glycoprotein biotherapeutics 112:139 N-glycosylation profiling of glycoprotein biotherapeutics is an essential step in each phase of product development in the biopharmaceutical industry. 26899450 7 29 from types 1117:1121 arg1 removal 1063:1069 efficient N-glycan removal 1044:1069 efficient N-glycan removal in 10min from all major N-linked glycoprotein types of: (i) neutral (IgG) 1044:1143 The use of PNGase F functionalized microcolumns resulted in efficient N-glycan removal in 10min from all major N-linked glycoprotein types of: (i) neutral (IgG), (ii) highly sialylated (fetuin), and (iii) high mannose (ribonuclease B) carbohydrate containing glycoprotein standards. 26899450 2 30 theme clones 283:288 arg1 hundreds 271:278 hundreds 271:278 hundreds of clones 271:288 For example, during clone selection, hundreds of clones should be analyzed quickly from limited amounts of samples. 26899450 1 31 theme development 187:197 arg1 phase 170:174 each phase 165:174 each phase of product development in the biopharmaceutical industry 165:231 N-glycosylation profiling of glycoprotein biotherapeutics is an essential step in each phase of product development in the biopharmaceutical industry. 26899450 0 32 theme N-glycan 6:13 arg1 release 15:21 Rapid N-glycan release 0:21 Rapid N-glycan release from glycoproteins 0:40 Rapid N-glycan release from glycoproteins using immobilized PNGase F microcolumns. 26899450 0 33 from glycoproteins 28:40 arg1 release 15:21 Rapid N-glycan release 0:21 Rapid N-glycan release from glycoproteins 0:40 Rapid N-glycan release from glycoproteins using immobilized PNGase F microcolumns. 26899450 5 34 gly glycoproteins 879:891 arg1 glycoproteins 879:891 glycoproteins 879:891 glycoproteins 879:891 In this paper, we report on the design and implementation of immobilized recombinant glutathione-S-transferase (GST) tagged PNGase F enzyme microcolumns for rapid and efficient removal of N-linked carbohydrates from glycoproteins. 26899450 1 35 from step 157:160 arg1 phase 170:174 each phase 165:174 each phase of product development in the biopharmaceutical industry 165:231 N-glycosylation profiling of glycoprotein biotherapeutics is an essential step in each phase of product development in the biopharmaceutical industry. 26899450 3 36 theme alterations 417:427 arg1 indicators 448:457 early indicators 442:457 early indicators (glycobiomarkers) for various pathological conditions in the biomedical field 442:535 On the other hand, identification of disease related glycosylation alterations can serve as early indicators (glycobiomarkers) for various pathological conditions in the biomedical field. 26899450 3 36 theme alterations 417:427 arg1 identification 369:382 identification 369:382 identification of disease related glycosylation alterations 369:427 On the other hand, identification of disease related glycosylation alterations can serve as early indicators (glycobiomarkers) for various pathological conditions in the biomedical field. 26899450 7 37 theme glycoprotein 1104:1115 arg1 types 1117:1121 all major N-linked glycoprotein types 1085:1121 all major N-linked glycoprotein types of: (i) neutral (IgG) 1085:1143 The use of PNGase F functionalized microcolumns resulted in efficient N-glycan removal in 10min from all major N-linked glycoprotein types of: (i) neutral (IgG), (ii) highly sialylated (fetuin), and (iii) high mannose (ribonuclease B) carbohydrate containing glycoprotein standards. 26899450 0 38 theme Rapid 0:4 arg1 release 15:21 Rapid N-glycan release 0:21 Rapid N-glycan release from glycoproteins 0:40 Rapid N-glycan release from glycoproteins using immobilized PNGase F microcolumns. 26899450 7 39 dep sialylated 1158:1167 arg1 fetuin 1170:1175 fetuin 1170:1175 fetuin 1170:1175 The use of PNGase F functionalized microcolumns resulted in efficient N-glycan removal in 10min from all major N-linked glycoprotein types of: (i) neutral (IgG), (ii) highly sialylated (fetuin), and (iii) high mannose (ribonuclease B) carbohydrate containing glycoprotein standards. 26899450 7 39 dep sialylated 1158:1167 arg1 ii 1147:1148 ii 1147:1148 ii 1147:1148 The use of PNGase F functionalized microcolumns resulted in efficient N-glycan removal in 10min from all major N-linked glycoprotein types of: (i) neutral (IgG), (ii) highly sialylated (fetuin), and (iii) high mannose (ribonuclease B) carbohydrate containing glycoprotein standards. 26899450 2 40 theme limited 322:328 arg1 samples 341:347 samples 341:347 samples 341:347 For example, during clone selection, hundreds of clones should be analyzed quickly from limited amounts of samples. 26899450 2 40 theme limited 322:328 arg1 amounts 330:336 limited amounts 322:336 limited amounts of samples 322:347 For example, during clone selection, hundreds of clones should be analyzed quickly from limited amounts of samples. 26899450 3 41 theme early 442:446 arg1 indicators 448:457 early indicators 442:457 early indicators (glycobiomarkers) for various pathological conditions in the biomedical field 442:535 On the other hand, identification of disease related glycosylation alterations can serve as early indicators (glycobiomarkers) for various pathological conditions in the biomedical field. 26899450 3 41 theme early 442:446 arg1 identification 369:382 identification 369:382 identification of disease related glycosylation alterations 369:427 On the other hand, identification of disease related glycosylation alterations can serve as early indicators (glycobiomarkers) for various pathological conditions in the biomedical field. 26899450 3 41 theme early 442:446 arg1 glycobiomarkers 460:474 glycobiomarkers 460:474 glycobiomarkers 460:474 On the other hand, identification of disease related glycosylation alterations can serve as early indicators (glycobiomarkers) for various pathological conditions in the biomedical field. 26899450 4 42 theme sample 606:611 arg1 preparation 613:623 sample preparation 606:623 sample preparation 606:623 Therefore, there is a growing demand for rapid and easy to automate sample preparation methods for N-glycosylation analysis. 26899450 4 43 theme growing 560:566 arg1 demand 568:573 a growing demand 558:573 a growing demand for rapid and easy to automate sample preparation methods for N-glycosylation analysis 558:660 Therefore, there is a growing demand for rapid and easy to automate sample preparation methods for N-glycosylation analysis. 26899450 7 44 theme F 1002:1002 arg1 microcolumns 1019:1030 PNGase F functionalized microcolumns 995:1030 PNGase F functionalized microcolumns 995:1030 The use of PNGase F functionalized microcolumns resulted in efficient N-glycan removal in 10min from all major N-linked glycoprotein types of: (i) neutral (IgG), (ii) highly sialylated (fetuin), and (iii) high mannose (ribonuclease B) carbohydrate containing glycoprotein standards. 26899450 1 45 theme glycoprotein 112:123 arg1 biotherapeutics 125:139 glycoprotein biotherapeutics 112:139 glycoprotein biotherapeutics 112:139 N-glycosylation profiling of glycoprotein biotherapeutics is an essential step in each phase of product development in the biopharmaceutical industry. 26899450 7 46 theme functionalized 1004:1017 arg1 microcolumns 1019:1030 PNGase F functionalized microcolumns 995:1030 PNGase F functionalized microcolumns 995:1030 The use of PNGase F functionalized microcolumns resulted in efficient N-glycan removal in 10min from all major N-linked glycoprotein types of: (i) neutral (IgG), (ii) highly sialylated (fetuin), and (iii) high mannose (ribonuclease B) carbohydrate containing glycoprotein standards. 26899450 1 47 theme biopharmaceutical 206:222 arg1 industry 224:231 the biopharmaceutical industry 202:231 the biopharmaceutical industry 202:231 N-glycosylation profiling of glycoprotein biotherapeutics is an essential step in each phase of product development in the biopharmaceutical industry. 26899450 7 48 theme N-glycan 1054:1061 arg1 removal 1063:1069 efficient N-glycan removal 1044:1069 efficient N-glycan removal in 10min from all major N-linked glycoprotein types of: (i) neutral (IgG) 1044:1143 The use of PNGase F functionalized microcolumns resulted in efficient N-glycan removal in 10min from all major N-linked glycoprotein types of: (i) neutral (IgG), (ii) highly sialylated (fetuin), and (iii) high mannose (ribonuclease B) carbohydrate containing glycoprotein standards. 26899450 4 49 theme rapid 579:583 arg1 methods 625:631 rapid and easy to automate sample preparation methods 579:631 rapid and easy to automate sample preparation methods 579:631 Therefore, there is a growing demand for rapid and easy to automate sample preparation methods for N-glycosylation analysis. 26899450 7 50 link N-linked 1095:1102 arg1 types 1117:1121 all major N-linked glycoprotein types 1085:1121 all major N-linked glycoprotein types of: (i) neutral (IgG) 1085:1143 The use of PNGase F functionalized microcolumns resulted in efficient N-glycan removal in 10min from all major N-linked glycoprotein types of: (i) neutral (IgG), (ii) highly sialylated (fetuin), and (iii) high mannose (ribonuclease B) carbohydrate containing glycoprotein standards. 26899450 1 51 theme biotherapeutics 125:139 arg1 step 157:160 an essential step 144:160 an essential step in each phase of product development in the biopharmaceutical industry 144:231 N-glycosylation profiling of glycoprotein biotherapeutics is an essential step in each phase of product development in the biopharmaceutical industry. 26899450 1 51 theme biotherapeutics 125:139 arg1 profiling 99:107 N-glycosylation profiling 83:107 N-glycosylation profiling of glycoprotein biotherapeutics 83:139 N-glycosylation profiling of glycoprotein biotherapeutics is an essential step in each phase of product development in the biopharmaceutical industry. 26899450 8 52 theme liquid 1352:1357 arg1 robots 1368:1373 liquid handling robots 1352:1373 liquid handling robots 1352:1373 The approach can be readily applied to automated sample preparation systems, such as liquid handling robots. 26899450 3 53 theme various 481:487 arg1 conditions 502:511 various pathological conditions 481:511 various pathological conditions in the biomedical field 481:535 On the other hand, identification of disease related glycosylation alterations can serve as early indicators (glycobiomarkers) for various pathological conditions in the biomedical field. 26899450 5 54 theme enzyme 796:801 arg1 microcolumns 803:814 immobilized recombinant glutathione-S-transferase (GST) tagged PNGase F enzyme microcolumns 724:814 immobilized recombinant glutathione-S-transferase (GST) tagged PNGase F enzyme microcolumns for rapid and efficient removal of N-linked carbohydrates from glycoproteins 724:891 In this paper, we report on the design and implementation of immobilized recombinant glutathione-S-transferase (GST) tagged PNGase F enzyme microcolumns for rapid and efficient removal of N-linked carbohydrates from glycoproteins. 26899450 2 55 theme clone 254:258 arg1 selection 260:268 clone selection 254:268 clone selection 254:268 For example, during clone selection, hundreds of clones should be analyzed quickly from limited amounts of samples. 26899450 5 56 theme microcolumns 803:814 arg1 implementation 706:719 implementation 706:719 implementation 706:719 In this paper, we report on the design and implementation of immobilized recombinant glutathione-S-transferase (GST) tagged PNGase F enzyme microcolumns for rapid and efficient removal of N-linked carbohydrates from glycoproteins. 26899450 5 56 theme microcolumns 803:814 arg1 design 695:700 design 695:700 design 695:700 In this paper, we report on the design and implementation of immobilized recombinant glutathione-S-transferase (GST) tagged PNGase F enzyme microcolumns for rapid and efficient removal of N-linked carbohydrates from glycoproteins. 26899450 5 57 theme immobilized 724:734 arg1 F 794:794 immobilized recombinant glutathione-S-transferase (GST) tagged PNGase F 724:794 immobilized recombinant glutathione-S-transferase (GST) tagged PNGase F enzyme microcolumns for rapid and efficient removal of N-linked carbohydrates from glycoproteins 724:891 In this paper, we report on the design and implementation of immobilized recombinant glutathione-S-transferase (GST) tagged PNGase F enzyme microcolumns for rapid and efficient removal of N-linked carbohydrates from glycoproteins. 26899450 6 58 theme Digestion 894:902 arg1 speed 904:908 Digestion speed 894:908 Digestion speed 894:908 Digestion speed and efficiency were compared to conventional in-solution based protocols. 26899450 7 59 theme major 1089:1093 arg1 types 1117:1121 all major N-linked glycoprotein types 1085:1121 all major N-linked glycoprotein types of: (i) neutral (IgG) 1085:1143 The use of PNGase F functionalized microcolumns resulted in efficient N-glycan removal in 10min from all major N-linked glycoprotein types of: (i) neutral (IgG), (ii) highly sialylated (fetuin), and (iii) high mannose (ribonuclease B) carbohydrate containing glycoprotein standards. 26899450 3 60 theme other 357:361 arg1 hand 363:366 the other hand 353:366 the other hand 353:366 On the other hand, identification of disease related glycosylation alterations can serve as early indicators (glycobiomarkers) for various pathological conditions in the biomedical field. 26899450 0 61 theme PNGase 60:65 arg1 F 67:67 PNGase F 60:67 immobilized PNGase F microcolumns 48:80 Rapid N-glycan release from glycoproteins using immobilized PNGase F microcolumns. 26899450 5 62 theme rapid 820:824 arg1 removal 840:846 rapid and efficient removal 820:846 rapid and efficient removal of N-linked carbohydrates from glycoproteins 820:891 In this paper, we report on the design and implementation of immobilized recombinant glutathione-S-transferase (GST) tagged PNGase F enzyme microcolumns for rapid and efficient removal of N-linked carbohydrates from glycoproteins. 26899450 5 63 theme tagged 780:785 arg1 F 794:794 immobilized recombinant glutathione-S-transferase (GST) tagged PNGase F 724:794 immobilized recombinant glutathione-S-transferase (GST) tagged PNGase F enzyme microcolumns for rapid and efficient removal of N-linked carbohydrates from glycoproteins 724:891 In this paper, we report on the design and implementation of immobilized recombinant glutathione-S-transferase (GST) tagged PNGase F enzyme microcolumns for rapid and efficient removal of N-linked carbohydrates from glycoproteins. 26899450 5 64 from glycoproteins 879:891 arg1 removal 840:846 rapid and efficient removal 820:846 rapid and efficient removal of N-linked carbohydrates from glycoproteins 820:891 In this paper, we report on the design and implementation of immobilized recombinant glutathione-S-transferase (GST) tagged PNGase F enzyme microcolumns for rapid and efficient removal of N-linked carbohydrates from glycoproteins. 26899450 5 64 from glycoproteins 879:891 arg1 carbohydrates 860:872 N-linked carbohydrates 851:872 N-linked carbohydrates from glycoproteins 851:891 In this paper, we report on the design and implementation of immobilized recombinant glutathione-S-transferase (GST) tagged PNGase F enzyme microcolumns for rapid and efficient removal of N-linked carbohydrates from glycoproteins. 26899450 7 65 gly glycoprotein 1104:1115 arg1 glycoprotein 1104:1115 all major N-linked glycoprotein types 1085:1121 all major N-linked glycoprotein types of: (i) neutral (IgG) 1085:1143 The use of PNGase F functionalized microcolumns resulted in efficient N-glycan removal in 10min from all major N-linked glycoprotein types of: (i) neutral (IgG), (ii) highly sialylated (fetuin), and (iii) high mannose (ribonuclease B) carbohydrate containing glycoprotein standards. 26899450 0 66 theme immobilized 48:58 arg1 microcolumns 69:80 immobilized PNGase F microcolumns 48:80 immobilized PNGase F microcolumns 48:80 Rapid N-glycan release from glycoproteins using immobilized PNGase F microcolumns. 26899450 3 67 theme pathological 489:500 arg1 conditions 502:511 various pathological conditions 481:511 various pathological conditions in the biomedical field 481:535 On the other hand, identification of disease related glycosylation alterations can serve as early indicators (glycobiomarkers) for various pathological conditions in the biomedical field. 26899450 0 68 gly glycoproteins 28:40 arg1 glycoproteins 28:40 glycoproteins 28:40 glycoproteins 28:40 Rapid N-glycan release from glycoproteins using immobilized PNGase F microcolumns. 26899450 7 69 theme microcolumns 1019:1030 arg1 use 988:990 The use 984:990 The use of PNGase F functionalized microcolumns 984:1030 The use of PNGase F functionalized microcolumns resulted in efficient N-glycan removal in 10min from all major N-linked glycoprotein types of: (i) neutral (IgG), (ii) highly sialylated (fetuin), and (iii) high mannose (ribonuclease B) carbohydrate containing glycoprotein standards. 26899450 1 70 theme essential 147:155 arg1 step 157:160 an essential step 144:160 an essential step in each phase of product development in the biopharmaceutical industry 144:231 N-glycosylation profiling of glycoprotein biotherapeutics is an essential step in each phase of product development in the biopharmaceutical industry. 26899450 1 70 theme essential 147:155 arg1 profiling 99:107 N-glycosylation profiling 83:107 N-glycosylation profiling of glycoprotein biotherapeutics 83:139 N-glycosylation profiling of glycoprotein biotherapeutics is an essential step in each phase of product development in the biopharmaceutical industry. 26899450 1 71 theme N-glycosylation 83:97 arg1 step 157:160 an essential step 144:160 an essential step in each phase of product development in the biopharmaceutical industry 144:231 N-glycosylation profiling of glycoprotein biotherapeutics is an essential step in each phase of product development in the biopharmaceutical industry. 26899450 1 71 theme N-glycosylation 83:97 arg1 profiling 99:107 N-glycosylation profiling 83:107 N-glycosylation profiling of glycoprotein biotherapeutics 83:139 N-glycosylation profiling of glycoprotein biotherapeutics is an essential step in each phase of product development in the biopharmaceutical industry. 26899450 7 72 theme efficient 1044:1052 arg1 removal 1063:1069 efficient N-glycan removal 1044:1069 efficient N-glycan removal in 10min from all major N-linked glycoprotein types of: (i) neutral (IgG) 1044:1143 The use of PNGase F functionalized microcolumns resulted in efficient N-glycan removal in 10min from all major N-linked glycoprotein types of: (i) neutral (IgG), (ii) highly sialylated (fetuin), and (iii) high mannose (ribonuclease B) carbohydrate containing glycoprotein standards. 26899450 8 73 theme sample 1316:1321 arg1 systems 1335:1341 automated sample preparation systems 1306:1341 automated sample preparation systems 1306:1341 The approach can be readily applied to automated sample preparation systems, such as liquid handling robots. 26899450 8 73 theme sample 1316:1321 arg1 robots 1368:1373 liquid handling robots 1352:1373 liquid handling robots 1352:1373 The approach can be readily applied to automated sample preparation systems, such as liquid handling robots. 26899450 2 74 theme samples 341:347 arg1 samples 341:347 samples 341:347 samples 341:347 For example, during clone selection, hundreds of clones should be analyzed quickly from limited amounts of samples. 26899450 2 74 theme samples 341:347 arg1 amounts 330:336 limited amounts 322:336 limited amounts of samples 322:347 For example, during clone selection, hundreds of clones should be analyzed quickly from limited amounts of samples. 26899450 7 75 dep types 1117:1121 arg1 neutral 1131:1137 neutral 1131:1137 neutral 1131:1137 The use of PNGase F functionalized microcolumns resulted in efficient N-glycan removal in 10min from all major N-linked glycoprotein types of: (i) neutral (IgG), (ii) highly sialylated (fetuin), and (iii) high mannose (ribonuclease B) carbohydrate containing glycoprotein standards. 26899450 7 75 dep types 1117:1121 arg1 IgG 1140:1142 IgG 1140:1142 IgG 1140:1142 The use of PNGase F functionalized microcolumns resulted in efficient N-glycan removal in 10min from all major N-linked glycoprotein types of: (i) neutral (IgG), (ii) highly sialylated (fetuin), and (iii) high mannose (ribonuclease B) carbohydrate containing glycoprotein standards. 26899450 7 76 theme N-linked 1095:1102 arg1 types 1117:1121 all major N-linked glycoprotein types 1085:1121 all major N-linked glycoprotein types of: (i) neutral (IgG) 1085:1143 The use of PNGase F functionalized microcolumns resulted in efficient N-glycan removal in 10min from all major N-linked glycoprotein types of: (i) neutral (IgG), (ii) highly sialylated (fetuin), and (iii) high mannose (ribonuclease B) carbohydrate containing glycoprotein standards. 26899450 5 77 theme N-linked 851:858 arg1 carbohydrates 860:872 N-linked carbohydrates 851:872 N-linked carbohydrates from glycoproteins 851:891 In this paper, we report on the design and implementation of immobilized recombinant glutathione-S-transferase (GST) tagged PNGase F enzyme microcolumns for rapid and efficient removal of N-linked carbohydrates from glycoproteins. 26899450 7 78 theme ribonuclease 1203:1214 arg1 carbohydrate 1219:1230 high mannose (ribonuclease B) carbohydrate 1189:1230 high mannose (ribonuclease B) carbohydrate 1189:1230 The use of PNGase F functionalized microcolumns resulted in efficient N-glycan removal in 10min from all major N-linked glycoprotein types of: (i) neutral (IgG), (ii) highly sialylated (fetuin), and (iii) high mannose (ribonuclease B) carbohydrate containing glycoprotein standards. 26899450 6 79 theme conventional 942:953 arg1 protocols 973:981 conventional in-solution based protocols 942:981 conventional in-solution based protocols 942:981 Digestion speed and efficiency were compared to conventional in-solution based protocols. 26899450 0 80 theme F 67:67 arg1 microcolumns 69:80 immobilized PNGase F microcolumns 48:80 immobilized PNGase F microcolumns 48:80 Rapid N-glycan release from glycoproteins using immobilized PNGase F microcolumns. 26899450 7 81 theme glycoprotein 1243:1254 arg1 standards 1256:1264 glycoprotein standards 1243:1264 glycoprotein standards 1243:1264 The use of PNGase F functionalized microcolumns resulted in efficient N-glycan removal in 10min from all major N-linked glycoprotein types of: (i) neutral (IgG), (ii) highly sialylated (fetuin), and (iii) high mannose (ribonuclease B) carbohydrate containing glycoprotein standards. 26899450 3 82 theme disease 387:393 arg1 alterations 417:427 disease related glycosylation alterations 387:427 disease related glycosylation alterations 387:427 On the other hand, identification of disease related glycosylation alterations can serve as early indicators (glycobiomarkers) for various pathological conditions in the biomedical field. 26899450 5 83 dep design 695:700 arg1 the 691:693 the 691:693 the 691:693 In this paper, we report on the design and implementation of immobilized recombinant glutathione-S-transferase (GST) tagged PNGase F enzyme microcolumns for rapid and efficient removal of N-linked carbohydrates from glycoproteins. 25998389 4 0 theme siRNA 832:836 arg1 transfection 838:849 triple siRNA transfection 825:849 triple siRNA transfection 825:849 All transfection groups showed effective reduction in 2,3-linked sialylation whereas the trend of reduction levels of triple siRNA transfection outweighed both the dual siRNA groups and single siRNA transfection groups. 25998389 8 1 link N-linked 1498:1505 arg1 sialylation 1507:1517 N-linked sialylation 1498:1517 N-linked sialylation 1498:1517 From these experiments, we concluded that each of these three genes were involved in N-linked sialylation and ST3GAL4 may play the critical role in glycoprotein sialylation of recombinant proteins such as EPO. 25998389 3 2 theme sialic 628:633 arg1 quantification 640:653 sialic acid quantification 628:653 sialic acid quantification 628:653 Single, double and triple gene knockdowns were investigated, and the reduction levels of sialylation on the total cell lysate were monitored by enzyme-linked lectin absorption assays (ELLA) and sialic acid quantification with high performance liquid chromatography (HPLC). 25998389 3 3 theme gene 460:463 arg1 knockdowns 465:474 Single, double and triple gene knockdowns 434:474 Single, double and triple gene knockdowns 434:474 Single, double and triple gene knockdowns were investigated, and the reduction levels of sialylation on the total cell lysate were monitored by enzyme-linked lectin absorption assays (ELLA) and sialic acid quantification with high performance liquid chromatography (HPLC). 25998389 3 4 with quantification 640:653 arg1 HPLC 700:703 HPLC 700:703 HPLC 700:703 Single, double and triple gene knockdowns were investigated, and the reduction levels of sialylation on the total cell lysate were monitored by enzyme-linked lectin absorption assays (ELLA) and sialic acid quantification with high performance liquid chromatography (HPLC). 25998389 3 4 with quantification 640:653 arg1 chromatography 684:697 high performance liquid chromatography 660:697 high performance liquid chromatography (HPLC) 660:704 Single, double and triple gene knockdowns were investigated, and the reduction levels of sialylation on the total cell lysate were monitored by enzyme-linked lectin absorption assays (ELLA) and sialic acid quantification with high performance liquid chromatography (HPLC). 25998389 3 5 theme liquid 677:682 arg1 HPLC 700:703 HPLC 700:703 HPLC 700:703 Single, double and triple gene knockdowns were investigated, and the reduction levels of sialylation on the total cell lysate were monitored by enzyme-linked lectin absorption assays (ELLA) and sialic acid quantification with high performance liquid chromatography (HPLC). 25998389 3 5 theme liquid 677:682 arg1 chromatography 684:697 high performance liquid chromatography 660:697 high performance liquid chromatography (HPLC) 660:704 Single, double and triple gene knockdowns were investigated, and the reduction levels of sialylation on the total cell lysate were monitored by enzyme-linked lectin absorption assays (ELLA) and sialic acid quantification with high performance liquid chromatography (HPLC). 25998389 4 6 theme reduction 805:813 arg1 levels 815:820 reduction levels 805:820 reduction levels of triple siRNA transfection 805:849 All transfection groups showed effective reduction in 2,3-linked sialylation whereas the trend of reduction levels of triple siRNA transfection outweighed both the dual siRNA groups and single siRNA transfection groups. 25998389 3 7 theme high 660:663 arg1 HPLC 700:703 HPLC 700:703 HPLC 700:703 Single, double and triple gene knockdowns were investigated, and the reduction levels of sialylation on the total cell lysate were monitored by enzyme-linked lectin absorption assays (ELLA) and sialic acid quantification with high performance liquid chromatography (HPLC). 25998389 3 7 theme high 660:663 arg1 chromatography 684:697 high performance liquid chromatography 660:697 high performance liquid chromatography (HPLC) 660:704 Single, double and triple gene knockdowns were investigated, and the reduction levels of sialylation on the total cell lysate were monitored by enzyme-linked lectin absorption assays (ELLA) and sialic acid quantification with high performance liquid chromatography (HPLC). 25998389 6 8 theme siRNA 1230:1234 arg1 transfections 1236:1248 other single siRNA transfections 1217:1248 other single siRNA transfections 1217:1248 Quantification of EPO sialylation showed similar result to total cell lysate except that the ST3GAL4 siRNA transfection exhibited the largest reduction according to the HPLC analysis as compared with other single siRNA transfections. 25998389 7 9 theme single 1385:1390 arg1 transfections 1398:1410 the single siRNA transfections 1381:1410 the single siRNA transfections 1381:1410 Finally, the N-glycan released from the EPO transfected with ST3GAL4 siRNA showed a prominent reduction in sialyation level among the single siRNA transfections. 25998389 6 10 theme other 1217:1221 arg1 transfections 1236:1248 other single siRNA transfections 1217:1248 other single siRNA transfections 1217:1248 Quantification of EPO sialylation showed similar result to total cell lysate except that the ST3GAL4 siRNA transfection exhibited the largest reduction according to the HPLC analysis as compared with other single siRNA transfections. 25998389 3 11 theme sialylation 523:533 arg1 levels 513:518 the reduction levels 499:518 the reduction levels of sialylation on the total cell lysate 499:558 Single, double and triple gene knockdowns were investigated, and the reduction levels of sialylation on the total cell lysate were monitored by enzyme-linked lectin absorption assays (ELLA) and sialic acid quantification with high performance liquid chromatography (HPLC). 25998389 6 12 theme ST3GAL4 1110:1116 arg1 transfection 1124:1135 the ST3GAL4 siRNA transfection 1106:1135 the ST3GAL4 siRNA transfection 1106:1135 Quantification of EPO sialylation showed similar result to total cell lysate except that the ST3GAL4 siRNA transfection exhibited the largest reduction according to the HPLC analysis as compared with other single siRNA transfections. 25998389 4 13 theme siRNA 900:904 arg1 groups 919:924 single siRNA transfection groups 893:924 single siRNA transfection groups 893:924 All transfection groups showed effective reduction in 2,3-linked sialylation whereas the trend of reduction levels of triple siRNA transfection outweighed both the dual siRNA groups and single siRNA transfection groups. 25998389 7 14 theme sialyation 1358:1367 arg1 level 1369:1373 sialyation level 1358:1373 sialyation level 1358:1373 Finally, the N-glycan released from the EPO transfected with ST3GAL4 siRNA showed a prominent reduction in sialyation level among the single siRNA transfections. 25998389 0 15 theme glycoproteins 112:124 arg1 linkage 91:97 the α2,3 sialylation linkage 70:97 the α2,3 sialylation linkage of mammalian glycoproteins 70:124 Assessment of the coordinated role of ST3GAL3, ST3GAL4 and ST3GAL6 on the α2,3 sialylation linkage of mammalian glycoproteins. 25998389 3 16 theme cell 548:551 arg1 lysate 553:558 the total cell lysate 538:558 the total cell lysate 538:558 Single, double and triple gene knockdowns were investigated, and the reduction levels of sialylation on the total cell lysate were monitored by enzyme-linked lectin absorption assays (ELLA) and sialic acid quantification with high performance liquid chromatography (HPLC). 25998389 1 17 theme N-linked 185:192 arg1 sialylation 194:204 N-linked sialylation 185:204 N-linked sialylation in Chinese Hamster Ovary (CHO) cells using siRNA knockdown approaches 185:274 In this research, we examined which genes are involved in N-linked sialylation in Chinese Hamster Ovary (CHO) cells using siRNA knockdown approaches. 25998389 4 18 theme siRNA 876:880 arg1 groups 882:887 the dual siRNA groups 867:887 the dual siRNA groups 867:887 All transfection groups showed effective reduction in 2,3-linked sialylation whereas the trend of reduction levels of triple siRNA transfection outweighed both the dual siRNA groups and single siRNA transfection groups. 25998389 6 19 theme HPLC 1186:1189 arg1 analysis 1191:1198 the HPLC analysis 1182:1198 the HPLC analysis 1182:1198 Quantification of EPO sialylation showed similar result to total cell lysate except that the ST3GAL4 siRNA transfection exhibited the largest reduction according to the HPLC analysis as compared with other single siRNA transfections. 25998389 3 20 from levels 513:518 arg1 lysate 553:558 the total cell lysate 538:558 the total cell lysate 538:558 Single, double and triple gene knockdowns were investigated, and the reduction levels of sialylation on the total cell lysate were monitored by enzyme-linked lectin absorption assays (ELLA) and sialic acid quantification with high performance liquid chromatography (HPLC). 25998389 0 21 theme ST3GAL4 47:53 arg1 role 30:33 the coordinated role 14:33 the coordinated role of ST3GAL3, ST3GAL4 and ST3GAL6 on the α2,3 sialylation linkage of mammalian glycoproteins 14:124 Assessment of the coordinated role of ST3GAL3, ST3GAL4 and ST3GAL6 on the α2,3 sialylation linkage of mammalian glycoproteins. 25998389 4 22 from reduction 748:756 arg1 sialylation 772:782 2,3-linked sialylation 761:782 2,3-linked sialylation 761:782 All transfection groups showed effective reduction in 2,3-linked sialylation whereas the trend of reduction levels of triple siRNA transfection outweighed both the dual siRNA groups and single siRNA transfection groups. 25998389 0 23 theme ST3GAL6 59:65 arg1 role 30:33 the coordinated role 14:33 the coordinated role of ST3GAL3, ST3GAL4 and ST3GAL6 on the α2,3 sialylation linkage of mammalian glycoproteins 14:124 Assessment of the coordinated role of ST3GAL3, ST3GAL4 and ST3GAL6 on the α2,3 sialylation linkage of mammalian glycoproteins. 25998389 0 24 from Assessment 0:9 arg1 linkage 91:97 the α2,3 sialylation linkage 70:97 the α2,3 sialylation linkage of mammalian glycoproteins 70:124 Assessment of the coordinated role of ST3GAL3, ST3GAL4 and ST3GAL6 on the α2,3 sialylation linkage of mammalian glycoproteins. 25998389 4 25 theme transfection 711:722 arg1 groups 724:729 All transfection groups 707:729 All transfection groups 707:729 All transfection groups showed effective reduction in 2,3-linked sialylation whereas the trend of reduction levels of triple siRNA transfection outweighed both the dual siRNA groups and single siRNA transfection groups. 25998389 0 26 theme sialylation 79:89 arg1 linkage 91:97 the α2,3 sialylation linkage 70:97 the α2,3 sialylation linkage of mammalian glycoproteins 70:124 Assessment of the coordinated role of ST3GAL3, ST3GAL4 and ST3GAL6 on the α2,3 sialylation linkage of mammalian glycoproteins. 25998389 6 27 theme sialylation 1039:1049 arg1 Quantification 1017:1030 Quantification 1017:1030 Quantification of EPO sialylation 1017:1049 Quantification of EPO sialylation showed similar result to total cell lysate except that the ST3GAL4 siRNA transfection exhibited the largest reduction according to the HPLC analysis as compared with other single siRNA transfections. 25998389 0 28 from role 30:33 arg1 linkage 91:97 the α2,3 sialylation linkage 70:97 the α2,3 sialylation linkage of mammalian glycoproteins 70:124 Assessment of the coordinated role of ST3GAL3, ST3GAL4 and ST3GAL6 on the α2,3 sialylation linkage of mammalian glycoproteins. 25998389 7 29 from reduction 1345:1353 arg1 level 1369:1373 sialyation level 1358:1373 sialyation level 1358:1373 Finally, the N-glycan released from the EPO transfected with ST3GAL4 siRNA showed a prominent reduction in sialyation level among the single siRNA transfections. 25998389 2 30 dep family 316:321 arg1 ST3GAL3 324:330 ST3GAL3 324:330 ST3GAL3 324:330 Three genes from the sialyltransferase family (ST3GAL3, ST3GAL4 and ST3GAL6) were chosen as knockdown targets with siRNA applied to reduce their expression. 25998389 2 30 dep family 316:321 arg1 ST3GAL6 345:351 ST3GAL6 345:351 ST3GAL6 345:351 Three genes from the sialyltransferase family (ST3GAL3, ST3GAL4 and ST3GAL6) were chosen as knockdown targets with siRNA applied to reduce their expression. 25998389 2 30 dep family 316:321 arg1 ST3GAL4 333:339 ST3GAL4 333:339 ST3GAL4 333:339 Three genes from the sialyltransferase family (ST3GAL3, ST3GAL4 and ST3GAL6) were chosen as knockdown targets with siRNA applied to reduce their expression. 25998389 1 31 theme siRNA 249:253 arg1 knockdown 255:263 siRNA knockdown 249:263 siRNA knockdown approaches 249:274 In this research, we examined which genes are involved in N-linked sialylation in Chinese Hamster Ovary (CHO) cells using siRNA knockdown approaches. 25998389 8 32 gly glycoprotein 1561:1572 arg1 glycoprotein 1561:1572 glycoprotein sialylation 1561:1584 glycoprotein sialylation of recombinant proteins such as EPO 1561:1620 From these experiments, we concluded that each of these three genes were involved in N-linked sialylation and ST3GAL4 may play the critical role in glycoprotein sialylation of recombinant proteins such as EPO. 25998389 0 33 theme role 30:33 arg1 Assessment 0:9 Assessment 0:9 Assessment of the coordinated role of ST3GAL3, ST3GAL4 and ST3GAL6 on the α2,3 sialylation linkage of mammalian glycoproteins. 0:125 Assessment of the coordinated role of ST3GAL3, ST3GAL4 and ST3GAL6 on the α2,3 sialylation linkage of mammalian glycoproteins. 25998389 8 34 theme critical 1544:1551 arg1 role 1553:1556 the critical role 1540:1556 the critical role 1540:1556 From these experiments, we concluded that each of these three genes were involved in N-linked sialylation and ST3GAL4 may play the critical role in glycoprotein sialylation of recombinant proteins such as EPO. 25998389 3 35 theme lectin 592:597 arg1 ELLA 618:621 ELLA 618:621 ELLA 618:621 Single, double and triple gene knockdowns were investigated, and the reduction levels of sialylation on the total cell lysate were monitored by enzyme-linked lectin absorption assays (ELLA) and sialic acid quantification with high performance liquid chromatography (HPLC). 25998389 3 35 theme lectin 592:597 arg1 assays 610:615 enzyme-linked lectin absorption assays 578:615 enzyme-linked lectin absorption assays (ELLA) 578:622 Single, double and triple gene knockdowns were investigated, and the reduction levels of sialylation on the total cell lysate were monitored by enzyme-linked lectin absorption assays (ELLA) and sialic acid quantification with high performance liquid chromatography (HPLC). 25998389 3 36 theme double 442:447 arg1 knockdowns 465:474 Single, double and triple gene knockdowns 434:474 Single, double and triple gene knockdowns 434:474 Single, double and triple gene knockdowns were investigated, and the reduction levels of sialylation on the total cell lysate were monitored by enzyme-linked lectin absorption assays (ELLA) and sialic acid quantification with high performance liquid chromatography (HPLC). 25998389 0 37 theme ST3GAL3 38:44 arg1 role 30:33 the coordinated role 14:33 the coordinated role of ST3GAL3, ST3GAL4 and ST3GAL6 on the α2,3 sialylation linkage of mammalian glycoproteins 14:124 Assessment of the coordinated role of ST3GAL3, ST3GAL4 and ST3GAL6 on the α2,3 sialylation linkage of mammalian glycoproteins. 25998389 7 38 attach released 1273:1280 arg2 N-glycan 1264:1271 the N-glycan 1260:1271 the N-glycan released from the EPO transfected with ST3GAL4 siRNA 1260:1324 Finally, the N-glycan released from the EPO transfected with ST3GAL4 siRNA showed a prominent reduction in sialyation level among the single siRNA transfections. 25998389 7 38 attach released 1273:1280 arg1 EPO 1291:1293 the EPO 1287:1293 the EPO transfected with ST3GAL4 siRNA 1287:1324 Finally, the N-glycan released from the EPO transfected with ST3GAL4 siRNA showed a prominent reduction in sialyation level among the single siRNA transfections. 25998389 3 39 theme Single 434:439 arg1 knockdowns 465:474 Single, double and triple gene knockdowns 434:474 Single, double and triple gene knockdowns 434:474 Single, double and triple gene knockdowns were investigated, and the reduction levels of sialylation on the total cell lysate were monitored by enzyme-linked lectin absorption assays (ELLA) and sialic acid quantification with high performance liquid chromatography (HPLC). 25998389 6 40 theme cell 1082:1085 arg1 lysate 1087:1092 total cell lysate 1076:1092 total cell lysate 1076:1092 Quantification of EPO sialylation showed similar result to total cell lysate except that the ST3GAL4 siRNA transfection exhibited the largest reduction according to the HPLC analysis as compared with other single siRNA transfections. 25998389 4 41 theme 2,3-linked 761:770 arg1 sialylation 772:782 2,3-linked sialylation 761:782 2,3-linked sialylation 761:782 All transfection groups showed effective reduction in 2,3-linked sialylation whereas the trend of reduction levels of triple siRNA transfection outweighed both the dual siRNA groups and single siRNA transfection groups. 25998389 1 42 theme Chinese 209:215 arg1 cells 237:241 Chinese Hamster Ovary (CHO) cells 209:241 Chinese Hamster Ovary (CHO) cells using siRNA knockdown approaches 209:274 In this research, we examined which genes are involved in N-linked sialylation in Chinese Hamster Ovary (CHO) cells using siRNA knockdown approaches. 25998389 5 43 theme CHO 975:977 arg1 cells 979:983 CHO cells 975:983 CHO cells producing erythropoietin (EPO) 975:1014 Next, this transfection approach was applied to CHO cells producing erythropoietin (EPO). 25998389 3 44 link enzyme-linked 578:590 arg1 ELLA 618:621 ELLA 618:621 ELLA 618:621 Single, double and triple gene knockdowns were investigated, and the reduction levels of sialylation on the total cell lysate were monitored by enzyme-linked lectin absorption assays (ELLA) and sialic acid quantification with high performance liquid chromatography (HPLC). 25998389 3 44 link enzyme-linked 578:590 arg1 assays 610:615 enzyme-linked lectin absorption assays 578:615 enzyme-linked lectin absorption assays (ELLA) 578:622 Single, double and triple gene knockdowns were investigated, and the reduction levels of sialylation on the total cell lysate were monitored by enzyme-linked lectin absorption assays (ELLA) and sialic acid quantification with high performance liquid chromatography (HPLC). 25998389 8 45 theme recombinant 1589:1599 arg1 proteins 1601:1608 recombinant proteins 1589:1608 recombinant proteins such as EPO 1589:1620 From these experiments, we concluded that each of these three genes were involved in N-linked sialylation and ST3GAL4 may play the critical role in glycoprotein sialylation of recombinant proteins such as EPO. 25998389 8 45 theme recombinant 1589:1599 arg1 EPO 1618:1620 EPO 1618:1620 EPO 1618:1620 From these experiments, we concluded that each of these three genes were involved in N-linked sialylation and ST3GAL4 may play the critical role in glycoprotein sialylation of recombinant proteins such as EPO. 25998389 3 46 theme triple 453:458 arg1 knockdowns 465:474 Single, double and triple gene knockdowns 434:474 Single, double and triple gene knockdowns 434:474 Single, double and triple gene knockdowns were investigated, and the reduction levels of sialylation on the total cell lysate were monitored by enzyme-linked lectin absorption assays (ELLA) and sialic acid quantification with high performance liquid chromatography (HPLC). 25998389 1 47 theme Ovary 225:229 arg1 cells 237:241 Chinese Hamster Ovary (CHO) cells 209:241 Chinese Hamster Ovary (CHO) cells using siRNA knockdown approaches 209:274 In this research, we examined which genes are involved in N-linked sialylation in Chinese Hamster Ovary (CHO) cells using siRNA knockdown approaches. 25998389 4 48 theme triple 825:830 arg1 transfection 838:849 triple siRNA transfection 825:849 triple siRNA transfection 825:849 All transfection groups showed effective reduction in 2,3-linked sialylation whereas the trend of reduction levels of triple siRNA transfection outweighed both the dual siRNA groups and single siRNA transfection groups. 25998389 6 49 theme similar 1058:1064 arg1 result 1066:1071 similar result 1058:1071 similar result 1058:1071 Quantification of EPO sialylation showed similar result to total cell lysate except that the ST3GAL4 siRNA transfection exhibited the largest reduction according to the HPLC analysis as compared with other single siRNA transfections. 25998389 3 50 theme acid 635:638 arg1 quantification 640:653 sialic acid quantification 628:653 sialic acid quantification 628:653 Single, double and triple gene knockdowns were investigated, and the reduction levels of sialylation on the total cell lysate were monitored by enzyme-linked lectin absorption assays (ELLA) and sialic acid quantification with high performance liquid chromatography (HPLC). 25998389 1 51 theme CHO 232:234 arg1 cells 237:241 Chinese Hamster Ovary (CHO) cells 209:241 Chinese Hamster Ovary (CHO) cells using siRNA knockdown approaches 209:274 In this research, we examined which genes are involved in N-linked sialylation in Chinese Hamster Ovary (CHO) cells using siRNA knockdown approaches. 25998389 4 52 theme transfection 838:849 arg1 levels 815:820 reduction levels 805:820 reduction levels of triple siRNA transfection 805:849 All transfection groups showed effective reduction in 2,3-linked sialylation whereas the trend of reduction levels of triple siRNA transfection outweighed both the dual siRNA groups and single siRNA transfection groups. 25998389 2 53 from family 316:321 arg1 targets 379:385 knockdown targets 369:385 knockdown targets with siRNA applied to reduce their expression 369:431 Three genes from the sialyltransferase family (ST3GAL3, ST3GAL4 and ST3GAL6) were chosen as knockdown targets with siRNA applied to reduce their expression. 25998389 2 53 from family 316:321 arg1 genes 283:287 Three genes 277:287 Three genes from the sialyltransferase family (ST3GAL3, ST3GAL4 and ST3GAL6) 277:352 Three genes from the sialyltransferase family (ST3GAL3, ST3GAL4 and ST3GAL6) were chosen as knockdown targets with siRNA applied to reduce their expression. 25998389 6 54 theme largest 1151:1157 arg1 reduction 1159:1167 the largest reduction 1147:1167 the largest reduction according to the HPLC analysis 1147:1198 Quantification of EPO sialylation showed similar result to total cell lysate except that the ST3GAL4 siRNA transfection exhibited the largest reduction according to the HPLC analysis as compared with other single siRNA transfections. 25998389 2 55 with targets 379:385 arg1 siRNA 392:396 siRNA 392:396 siRNA applied to reduce their expression 392:431 Three genes from the sialyltransferase family (ST3GAL3, ST3GAL4 and ST3GAL6) were chosen as knockdown targets with siRNA applied to reduce their expression. 25998389 3 56 theme performance 665:675 arg1 HPLC 700:703 HPLC 700:703 HPLC 700:703 Single, double and triple gene knockdowns were investigated, and the reduction levels of sialylation on the total cell lysate were monitored by enzyme-linked lectin absorption assays (ELLA) and sialic acid quantification with high performance liquid chromatography (HPLC). 25998389 3 56 theme performance 665:675 arg1 chromatography 684:697 high performance liquid chromatography 660:697 high performance liquid chromatography (HPLC) 660:704 Single, double and triple gene knockdowns were investigated, and the reduction levels of sialylation on the total cell lysate were monitored by enzyme-linked lectin absorption assays (ELLA) and sialic acid quantification with high performance liquid chromatography (HPLC). 25998389 6 57 theme single 1223:1228 arg1 transfections 1236:1248 other single siRNA transfections 1217:1248 other single siRNA transfections 1217:1248 Quantification of EPO sialylation showed similar result to total cell lysate except that the ST3GAL4 siRNA transfection exhibited the largest reduction according to the HPLC analysis as compared with other single siRNA transfections. 25998389 4 58 theme levels 815:820 arg1 trend 796:800 the trend 792:800 the trend of reduction levels of triple siRNA transfection 792:849 All transfection groups showed effective reduction in 2,3-linked sialylation whereas the trend of reduction levels of triple siRNA transfection outweighed both the dual siRNA groups and single siRNA transfection groups. 25998389 7 59 theme siRNA 1392:1396 arg1 transfections 1398:1410 the single siRNA transfections 1381:1410 the single siRNA transfections 1381:1410 Finally, the N-glycan released from the EPO transfected with ST3GAL4 siRNA showed a prominent reduction in sialyation level among the single siRNA transfections. 25998389 0 60 theme mammalian 102:110 arg1 glycoproteins 112:124 mammalian glycoproteins 102:124 mammalian glycoproteins 102:124 Assessment of the coordinated role of ST3GAL3, ST3GAL4 and ST3GAL6 on the α2,3 sialylation linkage of mammalian glycoproteins. 25998389 3 61 theme reduction 503:511 arg1 levels 513:518 the reduction levels 499:518 the reduction levels of sialylation on the total cell lysate 499:558 Single, double and triple gene knockdowns were investigated, and the reduction levels of sialylation on the total cell lysate were monitored by enzyme-linked lectin absorption assays (ELLA) and sialic acid quantification with high performance liquid chromatography (HPLC). 25998389 6 62 theme siRNA 1118:1122 arg1 transfection 1124:1135 the ST3GAL4 siRNA transfection 1106:1135 the ST3GAL4 siRNA transfection 1106:1135 Quantification of EPO sialylation showed similar result to total cell lysate except that the ST3GAL4 siRNA transfection exhibited the largest reduction according to the HPLC analysis as compared with other single siRNA transfections. 25998389 3 63 theme total 542:546 arg1 lysate 553:558 the total cell lysate 538:558 the total cell lysate 538:558 Single, double and triple gene knockdowns were investigated, and the reduction levels of sialylation on the total cell lysate were monitored by enzyme-linked lectin absorption assays (ELLA) and sialic acid quantification with high performance liquid chromatography (HPLC). 25998389 3 64 with assays 610:615 arg1 HPLC 700:703 HPLC 700:703 HPLC 700:703 Single, double and triple gene knockdowns were investigated, and the reduction levels of sialylation on the total cell lysate were monitored by enzyme-linked lectin absorption assays (ELLA) and sialic acid quantification with high performance liquid chromatography (HPLC). 25998389 3 64 with assays 610:615 arg1 chromatography 684:697 high performance liquid chromatography 660:697 high performance liquid chromatography (HPLC) 660:704 Single, double and triple gene knockdowns were investigated, and the reduction levels of sialylation on the total cell lysate were monitored by enzyme-linked lectin absorption assays (ELLA) and sialic acid quantification with high performance liquid chromatography (HPLC). 25998389 4 65 theme single 893:898 arg1 groups 919:924 single siRNA transfection groups 893:924 single siRNA transfection groups 893:924 All transfection groups showed effective reduction in 2,3-linked sialylation whereas the trend of reduction levels of triple siRNA transfection outweighed both the dual siRNA groups and single siRNA transfection groups. 25998389 0 66 from linkage 91:97 arg1 Assessment 0:9 Assessment 0:9 Assessment of the coordinated role of ST3GAL3, ST3GAL4 and ST3GAL6 on the α2,3 sialylation linkage of mammalian glycoproteins. 0:125 Assessment of the coordinated role of ST3GAL3, ST3GAL4 and ST3GAL6 on the α2,3 sialylation linkage of mammalian glycoproteins. 25998389 1 67 from sialylation 194:204 arg1 cells 237:241 Chinese Hamster Ovary (CHO) cells 209:241 Chinese Hamster Ovary (CHO) cells using siRNA knockdown approaches 209:274 In this research, we examined which genes are involved in N-linked sialylation in Chinese Hamster Ovary (CHO) cells using siRNA knockdown approaches. 25998389 0 68 gly glycoproteins 112:124 arg1 glycoproteins 112:124 mammalian glycoproteins 102:124 mammalian glycoproteins 102:124 Assessment of the coordinated role of ST3GAL3, ST3GAL4 and ST3GAL6 on the α2,3 sialylation linkage of mammalian glycoproteins. 25998389 4 69 theme dual 871:874 arg1 groups 882:887 the dual siRNA groups 867:887 the dual siRNA groups 867:887 All transfection groups showed effective reduction in 2,3-linked sialylation whereas the trend of reduction levels of triple siRNA transfection outweighed both the dual siRNA groups and single siRNA transfection groups. 25998389 7 70 theme prominent 1335:1343 arg1 reduction 1345:1353 a prominent reduction 1333:1353 a prominent reduction in sialyation level among the single siRNA transfections 1333:1410 Finally, the N-glycan released from the EPO transfected with ST3GAL4 siRNA showed a prominent reduction in sialyation level among the single siRNA transfections. 25998389 1 71 link N-linked 185:192 arg1 sialylation 194:204 N-linked sialylation 185:204 N-linked sialylation in Chinese Hamster Ovary (CHO) cells using siRNA knockdown approaches 185:274 In this research, we examined which genes are involved in N-linked sialylation in Chinese Hamster Ovary (CHO) cells using siRNA knockdown approaches. 25998389 0 72 theme α2,3 74:77 arg1 linkage 91:97 the α2,3 sialylation linkage 70:97 the α2,3 sialylation linkage of mammalian glycoproteins 70:124 Assessment of the coordinated role of ST3GAL3, ST3GAL4 and ST3GAL6 on the α2,3 sialylation linkage of mammalian glycoproteins. 25998389 1 73 gly sialylation 194:204 arg1 cells 237:241 Chinese Hamster Ovary (CHO) cells 209:241 Chinese Hamster Ovary (CHO) cells using siRNA knockdown approaches 209:274 In this research, we examined which genes are involved in N-linked sialylation in Chinese Hamster Ovary (CHO) cells using siRNA knockdown approaches. 25998389 4 74 theme transfection 906:917 arg1 groups 919:924 single siRNA transfection groups 893:924 single siRNA transfection groups 893:924 All transfection groups showed effective reduction in 2,3-linked sialylation whereas the trend of reduction levels of triple siRNA transfection outweighed both the dual siRNA groups and single siRNA transfection groups. 25998389 8 75 theme N-linked 1498:1505 arg1 sialylation 1507:1517 N-linked sialylation 1498:1517 N-linked sialylation 1498:1517 From these experiments, we concluded that each of these three genes were involved in N-linked sialylation and ST3GAL4 may play the critical role in glycoprotein sialylation of recombinant proteins such as EPO. 25998389 5 76 theme transfection 938:949 arg1 approach 951:958 this transfection approach 933:958 this transfection approach 933:958 Next, this transfection approach was applied to CHO cells producing erythropoietin (EPO). 25998389 6 77 theme EPO 1035:1037 arg1 sialylation 1039:1049 EPO sialylation 1035:1049 EPO sialylation 1035:1049 Quantification of EPO sialylation showed similar result to total cell lysate except that the ST3GAL4 siRNA transfection exhibited the largest reduction according to the HPLC analysis as compared with other single siRNA transfections. 25998389 0 78 theme coordinated 18:28 arg1 role 30:33 the coordinated role 14:33 the coordinated role of ST3GAL3, ST3GAL4 and ST3GAL6 on the α2,3 sialylation linkage of mammalian glycoproteins 14:124 Assessment of the coordinated role of ST3GAL3, ST3GAL4 and ST3GAL6 on the α2,3 sialylation linkage of mammalian glycoproteins. 25998389 4 79 link 2,3-linked 761:770 arg1 sialylation 772:782 2,3-linked sialylation 761:782 2,3-linked sialylation 761:782 All transfection groups showed effective reduction in 2,3-linked sialylation whereas the trend of reduction levels of triple siRNA transfection outweighed both the dual siRNA groups and single siRNA transfection groups. 25998389 3 80 theme absorption 599:608 arg1 ELLA 618:621 ELLA 618:621 ELLA 618:621 Single, double and triple gene knockdowns were investigated, and the reduction levels of sialylation on the total cell lysate were monitored by enzyme-linked lectin absorption assays (ELLA) and sialic acid quantification with high performance liquid chromatography (HPLC). 25998389 3 80 theme absorption 599:608 arg1 assays 610:615 enzyme-linked lectin absorption assays 578:615 enzyme-linked lectin absorption assays (ELLA) 578:622 Single, double and triple gene knockdowns were investigated, and the reduction levels of sialylation on the total cell lysate were monitored by enzyme-linked lectin absorption assays (ELLA) and sialic acid quantification with high performance liquid chromatography (HPLC). 25998389 2 81 theme knockdown 369:377 arg1 genes 283:287 Three genes 277:287 Three genes from the sialyltransferase family (ST3GAL3, ST3GAL4 and ST3GAL6) 277:352 Three genes from the sialyltransferase family (ST3GAL3, ST3GAL4 and ST3GAL6) were chosen as knockdown targets with siRNA applied to reduce their expression. 25998389 2 81 theme knockdown 369:377 arg1 targets 379:385 knockdown targets 369:385 knockdown targets with siRNA applied to reduce their expression 369:431 Three genes from the sialyltransferase family (ST3GAL3, ST3GAL4 and ST3GAL6) were chosen as knockdown targets with siRNA applied to reduce their expression. 25998389 1 82 theme knockdown 255:263 arg1 approaches 265:274 siRNA knockdown approaches 249:274 siRNA knockdown approaches 249:274 In this research, we examined which genes are involved in N-linked sialylation in Chinese Hamster Ovary (CHO) cells using siRNA knockdown approaches. 25998389 8 83 gly sialylation 1574:1584 arg1 proteins 1601:1608 recombinant proteins 1589:1608 recombinant proteins such as EPO 1589:1620 From these experiments, we concluded that each of these three genes were involved in N-linked sialylation and ST3GAL4 may play the critical role in glycoprotein sialylation of recombinant proteins such as EPO. 25998389 8 83 gly sialylation 1574:1584 arg1 EPO 1618:1620 EPO 1618:1620 EPO 1618:1620 From these experiments, we concluded that each of these three genes were involved in N-linked sialylation and ST3GAL4 may play the critical role in glycoprotein sialylation of recombinant proteins such as EPO. 25998389 3 84 theme enzyme-linked 578:590 arg1 ELLA 618:621 ELLA 618:621 ELLA 618:621 Single, double and triple gene knockdowns were investigated, and the reduction levels of sialylation on the total cell lysate were monitored by enzyme-linked lectin absorption assays (ELLA) and sialic acid quantification with high performance liquid chromatography (HPLC). 25998389 3 84 theme enzyme-linked 578:590 arg1 assays 610:615 enzyme-linked lectin absorption assays 578:615 enzyme-linked lectin absorption assays (ELLA) 578:622 Single, double and triple gene knockdowns were investigated, and the reduction levels of sialylation on the total cell lysate were monitored by enzyme-linked lectin absorption assays (ELLA) and sialic acid quantification with high performance liquid chromatography (HPLC). 25998389 8 85 theme glycoprotein 1561:1572 arg1 sialylation 1574:1584 glycoprotein sialylation 1561:1584 glycoprotein sialylation of recombinant proteins such as EPO 1561:1620 From these experiments, we concluded that each of these three genes were involved in N-linked sialylation and ST3GAL4 may play the critical role in glycoprotein sialylation of recombinant proteins such as EPO. 25998389 2 86 theme sialyltransferase 298:314 arg1 family 316:321 the sialyltransferase family 294:321 the sialyltransferase family (ST3GAL3, ST3GAL4 and ST3GAL6) 294:352 Three genes from the sialyltransferase family (ST3GAL3, ST3GAL4 and ST3GAL6) were chosen as knockdown targets with siRNA applied to reduce their expression. 25998389 4 87 theme effective 738:746 arg1 reduction 748:756 effective reduction 738:756 effective reduction in 2,3-linked sialylation 738:782 All transfection groups showed effective reduction in 2,3-linked sialylation whereas the trend of reduction levels of triple siRNA transfection outweighed both the dual siRNA groups and single siRNA transfection groups. 25998389 6 88 theme total 1076:1080 arg1 lysate 1087:1092 total cell lysate 1076:1092 total cell lysate 1076:1092 Quantification of EPO sialylation showed similar result to total cell lysate except that the ST3GAL4 siRNA transfection exhibited the largest reduction according to the HPLC analysis as compared with other single siRNA transfections. 25998389 7 89 theme ST3GAL4 1312:1318 arg1 siRNA 1320:1324 ST3GAL4 siRNA 1312:1324 ST3GAL4 siRNA 1312:1324 Finally, the N-glycan released from the EPO transfected with ST3GAL4 siRNA showed a prominent reduction in sialyation level among the single siRNA transfections. 25998389 8 90 theme proteins 1601:1608 arg1 sialylation 1574:1584 glycoprotein sialylation 1561:1584 glycoprotein sialylation of recombinant proteins such as EPO 1561:1620 From these experiments, we concluded that each of these three genes were involved in N-linked sialylation and ST3GAL4 may play the critical role in glycoprotein sialylation of recombinant proteins such as EPO. 25998389 1 91 theme Hamster 217:223 arg1 cells 237:241 Chinese Hamster Ovary (CHO) cells 209:241 Chinese Hamster Ovary (CHO) cells using siRNA knockdown approaches 209:274 In this research, we examined which genes are involved in N-linked sialylation in Chinese Hamster Ovary (CHO) cells using siRNA knockdown approaches. 28860471 9 0 theme AutoTip 1138:1144 arg1 reproducibility 1115:1129 the reproducibility 1111:1129 the reproducibility of the AutoTip 1111:1144 We first optimized our automated protocol using bovine fetuin as a standard glycoprotein, and then assessed the reproducibility of the AutoTip using isobaric tags for relative N-linked glycan quantification. 28860471 5 1 theme spin-column 639:649 arg1 format 658:663 a snap-cap spin-column (SCSC) format 628:663 a snap-cap spin-column (SCSC) format 628:663 Previously, sample preparation was successfully performed in a snap-cap spin-column (SCSC) format. 28860471 1 2 theme reproducible 156:167 arg1 method 169:174 an efficient, rapid and reproducible method 132:174 an efficient, rapid and reproducible method 132:174 Analysis of a large number of samples requires an efficient, rapid and reproducible method. 28860471 10 3 attach derived 1364:1370 arg2 N-glycans 1354:1362 urinary N-glycans 1346:1362 urinary N-glycans derived from prostate cancer patients 1346:1400 We then applied this methodology to profile N-glycans from 58 prostate cancer patient urine samples, revealing increased sialyation on urinary N-glycans derived from prostate cancer patients. 28860471 10 3 attach derived 1364:1370 arg1 patients 1393:1400 prostate cancer patients 1377:1400 prostate cancer patients 1377:1400 We then applied this methodology to profile N-glycans from 58 prostate cancer patient urine samples, revealing increased sialyation on urinary N-glycans derived from prostate cancer patients. 28860471 11 4 contain has 1433:1435 arg2 applications 1437:1448 applications 1437:1448 applications for high-throughput sample preparation for studying the N-linked glycans 1437:1521 Our results indicated AutoTip has applications for high-throughput sample preparation for studying the N-linked glycans. 28860471 11 4 contain has 1433:1435 arg1 AutoTip 1425:1431 AutoTip 1425:1431 AutoTip 1425:1431 Our results indicated AutoTip has applications for high-throughput sample preparation for studying the N-linked glycans. 28860471 10 5 theme urine 1297:1301 arg1 samples 1303:1309 58 prostate cancer patient urine samples 1270:1309 58 prostate cancer patient urine samples 1270:1309 We then applied this methodology to profile N-glycans from 58 prostate cancer patient urine samples, revealing increased sialyation on urinary N-glycans derived from prostate cancer patients. 28860471 10 6 theme profile 1247:1253 arg1 N-glycans 1255:1263 profile N-glycans 1247:1263 profile N-glycans from 58 prostate cancer patient urine samples 1247:1309 We then applied this methodology to profile N-glycans from 58 prostate cancer patient urine samples, revealing increased sialyation on urinary N-glycans derived from prostate cancer patients. 28860471 9 7 theme glycan 1188:1193 arg1 quantification 1195:1208 relative N-linked glycan quantification 1170:1208 relative N-linked glycan quantification 1170:1208 We first optimized our automated protocol using bovine fetuin as a standard glycoprotein, and then assessed the reproducibility of the AutoTip using isobaric tags for relative N-linked glycan quantification. 28860471 11 8 link N-linked 1506:1513 arg1 glycans 1515:1521 the N-linked glycans 1502:1521 the N-linked glycans 1502:1521 Our results indicated AutoTip has applications for high-throughput sample preparation for studying the N-linked glycans. 28860471 5 9 theme SCSC 652:655 arg1 format 658:663 a snap-cap spin-column (SCSC) format 628:663 a snap-cap spin-column (SCSC) format 628:663 Previously, sample preparation was successfully performed in a snap-cap spin-column (SCSC) format. 28860471 10 10 theme urinary 1346:1352 arg1 N-glycans 1354:1362 urinary N-glycans 1346:1362 urinary N-glycans derived from prostate cancer patients 1346:1400 We then applied this methodology to profile N-glycans from 58 prostate cancer patient urine samples, revealing increased sialyation on urinary N-glycans derived from prostate cancer patients. 28860471 10 11 theme increased 1322:1330 arg1 sialyation 1332:1341 increased sialyation 1322:1341 increased sialyation on urinary N-glycans derived from prostate cancer patients 1322:1400 We then applied this methodology to profile N-glycans from 58 prostate cancer patient urine samples, revealing increased sialyation on urinary N-glycans derived from prostate cancer patients. 28860471 9 12 gly glycoprotein 1079:1090 arg1 fetuin 1058:1063 bovine fetuin 1051:1063 bovine fetuin 1051:1063 We first optimized our automated protocol using bovine fetuin as a standard glycoprotein, and then assessed the reproducibility of the AutoTip using isobaric tags for relative N-linked glycan quantification. 28860471 9 12 gly glycoprotein 1079:1090 arg1 glycoprotein 1079:1090 a standard glycoprotein 1068:1090 a standard glycoprotein 1068:1090 We first optimized our automated protocol using bovine fetuin as a standard glycoprotein, and then assessed the reproducibility of the AutoTip using isobaric tags for relative N-linked glycan quantification. 28860471 0 13 theme High-throughput 0:14 arg1 analysis 16:23 High-throughput analysis 0:23 High-throughput analysis of N-glycans 0:36 High-throughput analysis of N-glycans using AutoTip via glycoprotein immobilization. 28860471 7 14 theme liquid 868:873 arg1 handler 875:881 an automated liquid handler 855:881 an automated liquid handler 855:881 In this work, we integrated the chemoenzymatic technique in a pipette tip (AutoTip) that was operated by an automated liquid handler. 28860471 3 15 theme several 394:400 arg1 steps 410:414 several cleanup steps 394:414 several cleanup steps 394:414 Multi-plexing sample preparation via a 96-well plate format becomes popular in recent years; however, those methods lack specificity and require several cleanup steps via chromatography purification. 28860471 3 16 theme Multi-plexing 249:261 arg1 preparation 270:280 Multi-plexing sample preparation 249:280 Multi-plexing sample preparation via a 96-well plate format 249:307 Multi-plexing sample preparation via a 96-well plate format becomes popular in recent years; however, those methods lack specificity and require several cleanup steps via chromatography purification. 28860471 10 17 from samples 1303:1309 arg1 N-glycans 1255:1263 profile N-glycans 1247:1263 profile N-glycans from 58 prostate cancer patient urine samples 1247:1309 We then applied this methodology to profile N-glycans from 58 prostate cancer patient urine samples, revealing increased sialyation on urinary N-glycans derived from prostate cancer patients. 28860471 8 18 theme multi-step 901:910 arg1 protocol 912:919 a multi-step protocol 899:919 a multi-step protocol involving protein immobilization, sialic acid modification, and N-glycan release 899:1000 We established a multi-step protocol involving protein immobilization, sialic acid modification, and N-glycan release. 28860471 3 19 theme cleanup 402:408 arg1 steps 410:414 several cleanup steps 394:414 several cleanup steps 394:414 Multi-plexing sample preparation via a 96-well plate format becomes popular in recent years; however, those methods lack specificity and require several cleanup steps via chromatography purification. 28860471 3 20 theme sample 263:268 arg1 preparation 270:280 Multi-plexing sample preparation 249:280 Multi-plexing sample preparation via a 96-well plate format 249:307 Multi-plexing sample preparation via a 96-well plate format becomes popular in recent years; however, those methods lack specificity and require several cleanup steps via chromatography purification. 28860471 1 21 theme large 99:103 arg1 number 105:110 a large number 97:110 a large number of samples 97:121 Analysis of a large number of samples requires an efficient, rapid and reproducible method. 28860471 8 22 theme protein 931:937 arg1 immobilization 939:952 protein immobilization 931:952 protein immobilization 931:952 We established a multi-step protocol involving protein immobilization, sialic acid modification, and N-glycan release. 28860471 0 23 theme N-glycans 28:36 arg1 analysis 16:23 High-throughput analysis 0:23 High-throughput analysis of N-glycans 0:36 High-throughput analysis of N-glycans using AutoTip via glycoprotein immobilization. 28860471 3 24 theme plate 296:300 arg1 format 302:307 a 96-well plate format 286:307 a 96-well plate format 286:307 Multi-plexing sample preparation via a 96-well plate format becomes popular in recent years; however, those methods lack specificity and require several cleanup steps via chromatography purification. 28860471 5 25 theme snap-cap 630:637 arg1 format 658:663 a snap-cap spin-column (SCSC) format 628:663 a snap-cap spin-column (SCSC) format 628:663 Previously, sample preparation was successfully performed in a snap-cap spin-column (SCSC) format. 28860471 1 26 theme number 105:110 arg1 Analysis 85:92 Analysis 85:92 Analysis of a large number of samples 85:121 Analysis of a large number of samples requires an efficient, rapid and reproducible method. 28860471 7 27 theme automated 858:866 arg1 handler 875:881 an automated liquid handler 855:881 an automated liquid handler 855:881 In this work, we integrated the chemoenzymatic technique in a pipette tip (AutoTip) that was operated by an automated liquid handler. 28860471 9 28 theme isobaric 1152:1159 arg1 tags 1161:1164 isobaric tags 1152:1164 isobaric tags for relative N-linked glycan quantification 1152:1208 We first optimized our automated protocol using bovine fetuin as a standard glycoprotein, and then assessed the reproducibility of the AutoTip using isobaric tags for relative N-linked glycan quantification. 28860471 9 29 theme automated 1026:1034 arg1 protocol 1036:1043 our automated protocol 1022:1043 our automated protocol using bovine fetuin as a standard glycoprotein 1022:1090 We first optimized our automated protocol using bovine fetuin as a standard glycoprotein, and then assessed the reproducibility of the AutoTip using isobaric tags for relative N-linked glycan quantification. 28860471 10 30 theme prostate 1377:1384 arg1 patients 1393:1400 prostate cancer patients 1377:1400 prostate cancer patients 1377:1400 We then applied this methodology to profile N-glycans from 58 prostate cancer patient urine samples, revealing increased sialyation on urinary N-glycans derived from prostate cancer patients. 28860471 3 31 theme chromatography 420:433 arg1 purification 435:446 chromatography purification 420:446 chromatography purification 420:446 Multi-plexing sample preparation via a 96-well plate format becomes popular in recent years; however, those methods lack specificity and require several cleanup steps via chromatography purification. 28860471 10 32 from sialyation 1332:1341 arg1 N-glycans 1354:1362 urinary N-glycans 1346:1362 urinary N-glycans derived from prostate cancer patients 1346:1400 We then applied this methodology to profile N-glycans from 58 prostate cancer patient urine samples, revealing increased sialyation on urinary N-glycans derived from prostate cancer patients. 28860471 9 33 theme standard 1070:1077 arg1 fetuin 1058:1063 bovine fetuin 1051:1063 bovine fetuin 1051:1063 We first optimized our automated protocol using bovine fetuin as a standard glycoprotein, and then assessed the reproducibility of the AutoTip using isobaric tags for relative N-linked glycan quantification. 28860471 9 33 theme standard 1070:1077 arg1 glycoprotein 1079:1090 a standard glycoprotein 1068:1090 a standard glycoprotein 1068:1090 We first optimized our automated protocol using bovine fetuin as a standard glycoprotein, and then assessed the reproducibility of the AutoTip using isobaric tags for relative N-linked glycan quantification. 28860471 3 34 theme 96-well 288:294 arg1 format 302:307 a 96-well plate format 286:307 a 96-well plate format 286:307 Multi-plexing sample preparation via a 96-well plate format becomes popular in recent years; however, those methods lack specificity and require several cleanup steps via chromatography purification. 28860471 4 35 theme chemoenzymatic 480:493 arg1 method 495:500 a chemoenzymatic method 478:500 a chemoenzymatic method 478:500 To overcome these drawbacks, a chemoenzymatic method has been developed utilizing protein conjugation on solid-phase. 28860471 5 36 theme sample 579:584 arg1 preparation 586:596 sample preparation 579:596 sample preparation 579:596 Previously, sample preparation was successfully performed in a snap-cap spin-column (SCSC) format. 28860471 0 37 theme glycoprotein 56:67 arg1 immobilization 69:82 glycoprotein immobilization 56:82 glycoprotein immobilization 56:82 High-throughput analysis of N-glycans using AutoTip via glycoprotein immobilization. 28860471 9 38 link N-linked 1179:1186 arg1 quantification 1195:1208 relative N-linked glycan quantification 1170:1208 relative N-linked glycan quantification 1170:1208 We first optimized our automated protocol using bovine fetuin as a standard glycoprotein, and then assessed the reproducibility of the AutoTip using isobaric tags for relative N-linked glycan quantification. 28860471 2 39 theme sample 229:234 arg1 preparation 236:246 high-throughput sample preparation 213:246 high-throughput sample preparation 213:246 Automation is an ideal approach for high-throughput sample preparation. 28860471 8 40 theme sialic 955:960 arg1 modification 967:978 sialic acid modification 955:978 sialic acid modification 955:978 We established a multi-step protocol involving protein immobilization, sialic acid modification, and N-glycan release. 28860471 1 41 theme samples 115:121 arg1 number 105:110 a large number 97:110 a large number of samples 97:121 Analysis of a large number of samples requires an efficient, rapid and reproducible method. 28860471 9 42 theme bovine 1051:1056 arg1 fetuin 1058:1063 bovine fetuin 1051:1063 bovine fetuin 1051:1063 We first optimized our automated protocol using bovine fetuin as a standard glycoprotein, and then assessed the reproducibility of the AutoTip using isobaric tags for relative N-linked glycan quantification. 28860471 9 42 theme bovine 1051:1056 arg1 glycoprotein 1079:1090 a standard glycoprotein 1068:1090 a standard glycoprotein 1068:1090 We first optimized our automated protocol using bovine fetuin as a standard glycoprotein, and then assessed the reproducibility of the AutoTip using isobaric tags for relative N-linked glycan quantification. 28860471 3 43 theme recent 328:333 arg1 years 335:339 recent years 328:339 recent years 328:339 Multi-plexing sample preparation via a 96-well plate format becomes popular in recent years; however, those methods lack specificity and require several cleanup steps via chromatography purification. 28860471 2 44 theme high-throughput 213:227 arg1 preparation 236:246 high-throughput sample preparation 213:246 high-throughput sample preparation 213:246 Automation is an ideal approach for high-throughput sample preparation. 28860471 9 45 theme relative 1170:1177 arg1 quantification 1195:1208 relative N-linked glycan quantification 1170:1208 relative N-linked glycan quantification 1170:1208 We first optimized our automated protocol using bovine fetuin as a standard glycoprotein, and then assessed the reproducibility of the AutoTip using isobaric tags for relative N-linked glycan quantification. 28860471 10 46 theme patient 1289:1295 arg1 samples 1303:1309 58 prostate cancer patient urine samples 1270:1309 58 prostate cancer patient urine samples 1270:1309 We then applied this methodology to profile N-glycans from 58 prostate cancer patient urine samples, revealing increased sialyation on urinary N-glycans derived from prostate cancer patients. 28860471 7 47 theme pipette 812:818 arg1 tip 820:822 a pipette tip 810:822 a pipette tip (AutoTip) 810:832 In this work, we integrated the chemoenzymatic technique in a pipette tip (AutoTip) that was operated by an automated liquid handler. 28860471 7 47 theme pipette 812:818 arg1 AutoTip 825:831 AutoTip 825:831 AutoTip 825:831 In this work, we integrated the chemoenzymatic technique in a pipette tip (AutoTip) that was operated by an automated liquid handler. 28860471 7 48 from technique 797:805 arg1 tip 820:822 a pipette tip 810:822 a pipette tip (AutoTip) 810:832 In this work, we integrated the chemoenzymatic technique in a pipette tip (AutoTip) that was operated by an automated liquid handler. 28860471 7 48 from technique 797:805 arg1 AutoTip 825:831 AutoTip 825:831 AutoTip 825:831 In this work, we integrated the chemoenzymatic technique in a pipette tip (AutoTip) that was operated by an automated liquid handler. 28860471 9 49 theme N-linked 1179:1186 arg1 quantification 1195:1208 relative N-linked glycan quantification 1170:1208 relative N-linked glycan quantification 1170:1208 We first optimized our automated protocol using bovine fetuin as a standard glycoprotein, and then assessed the reproducibility of the AutoTip using isobaric tags for relative N-linked glycan quantification. 28860471 10 50 theme cancer 1282:1287 arg1 samples 1303:1309 58 prostate cancer patient urine samples 1270:1309 58 prostate cancer patient urine samples 1270:1309 We then applied this methodology to profile N-glycans from 58 prostate cancer patient urine samples, revealing increased sialyation on urinary N-glycans derived from prostate cancer patients. 28860471 10 51 theme cancer 1386:1391 arg1 patients 1393:1400 prostate cancer patients 1377:1400 prostate cancer patients 1377:1400 We then applied this methodology to profile N-glycans from 58 prostate cancer patient urine samples, revealing increased sialyation on urinary N-glycans derived from prostate cancer patients. 28860471 2 52 theme ideal 194:198 arg1 Automation 177:186 Automation 177:186 Automation 177:186 Automation is an ideal approach for high-throughput sample preparation. 28860471 2 52 theme ideal 194:198 arg1 approach 200:207 an ideal approach 191:207 an ideal approach for high-throughput sample preparation 191:246 Automation is an ideal approach for high-throughput sample preparation. 28860471 8 53 theme acid 962:965 arg1 modification 967:978 sialic acid modification 955:978 sialic acid modification 955:978 We established a multi-step protocol involving protein immobilization, sialic acid modification, and N-glycan release. 28860471 8 54 theme N-glycan 985:992 arg1 release 994:1000 N-glycan release 985:1000 N-glycan release 985:1000 We established a multi-step protocol involving protein immobilization, sialic acid modification, and N-glycan release. 28860471 1 55 theme efficient 135:143 arg1 method 169:174 an efficient, rapid and reproducible method 132:174 an efficient, rapid and reproducible method 132:174 Analysis of a large number of samples requires an efficient, rapid and reproducible method. 28860471 10 56 theme prostate 1273:1280 arg1 samples 1303:1309 58 prostate cancer patient urine samples 1270:1309 58 prostate cancer patient urine samples 1270:1309 We then applied this methodology to profile N-glycans from 58 prostate cancer patient urine samples, revealing increased sialyation on urinary N-glycans derived from prostate cancer patients. 28860471 11 57 theme N-linked 1506:1513 arg1 glycans 1515:1521 the N-linked glycans 1502:1521 the N-linked glycans 1502:1521 Our results indicated AutoTip has applications for high-throughput sample preparation for studying the N-linked glycans. 28860471 11 58 theme high-throughput 1454:1468 arg1 preparation 1477:1487 high-throughput sample preparation 1454:1487 high-throughput sample preparation 1454:1487 Our results indicated AutoTip has applications for high-throughput sample preparation for studying the N-linked glycans. 28860471 6 59 theme sample 675:680 arg1 preparation 682:692 sample preparation 675:692 sample preparation using SCSC 675:703 However, sample preparation using SCSC is time-consuming and lacks reproducibility. 28860471 11 60 theme sample 1470:1475 arg1 preparation 1477:1487 high-throughput sample preparation 1454:1487 high-throughput sample preparation 1454:1487 Our results indicated AutoTip has applications for high-throughput sample preparation for studying the N-linked glycans. 28860471 4 61 theme protein 531:537 arg1 conjugation 539:549 protein conjugation 531:549 protein conjugation 531:549 To overcome these drawbacks, a chemoenzymatic method has been developed utilizing protein conjugation on solid-phase. 28860471 0 62 gly glycoprotein 56:67 arg1 glycoprotein 56:67 glycoprotein immobilization 56:82 glycoprotein immobilization 56:82 High-throughput analysis of N-glycans using AutoTip via glycoprotein immobilization. 28860471 1 63 theme rapid 146:150 arg1 method 169:174 an efficient, rapid and reproducible method 132:174 an efficient, rapid and reproducible method 132:174 Analysis of a large number of samples requires an efficient, rapid and reproducible method. 28860471 7 64 theme chemoenzymatic 782:795 arg1 technique 797:805 the chemoenzymatic technique 778:805 the chemoenzymatic technique in a pipette tip (AutoTip) that was operated by an automated liquid handler 778:881 In this work, we integrated the chemoenzymatic technique in a pipette tip (AutoTip) that was operated by an automated liquid handler. 26589799 0 0 theme Cycle 70:74 arg1 Progression 76:86 Cell Cycle Progression 65:86 Cell Cycle Progression 65:86 MicroRNA-424 Predicts a Role for β-1,4 Branched Glycosylation in Cell Cycle Progression. 26589799 7 1 from changes 1093:1099 arg1 glycosylation 1121:1133 overall N-linked glycosylation 1104:1133 overall N-linked glycosylation 1104:1133 MGAT4A does not affect levels of β-1,6 branched N-glycans, arguing that this effect is specific to β-1,4 branching and not due to gross changes in overall N-linked glycosylation. 26589799 7 2 theme β-1,4 1056:1060 arg1 branching 1062:1070 β-1,4 branching 1056:1070 β-1,4 branching 1056:1070 MGAT4A does not affect levels of β-1,6 branched N-glycans, arguing that this effect is specific to β-1,4 branching and not due to gross changes in overall N-linked glycosylation. 26589799 3 3 theme biological 497:506 arg1 roles 508:512 biological roles 497:512 biological roles of glycosylation enzymes (glycogenes) 497:550 Our laboratory recently established that microRNA can be used as a proxy to identify biological roles of glycosylation enzymes (glycogenes). 26589799 3 4 theme enzymes 531:537 arg1 roles 508:512 biological roles 497:512 biological roles of glycosylation enzymes (glycogenes) 497:550 Our laboratory recently established that microRNA can be used as a proxy to identify biological roles of glycosylation enzymes (glycogenes). 26589799 6 5 theme CCND1 943:947 arg1 levels 949:954 CCND1 levels 943:954 CCND1 levels 943:954 Knockdown of MGAT4A induces cell cycle arrest through decreasing CCND1 levels. 26589799 5 6 theme N-glycans 717:725 arg1 branch 707:712 the β-1,4 branch 697:712 the β-1,4 branch of N-glycans 697:725 We demonstrate that MGAT4A, an N-acetylglucosaminyltransferase that installs the β-1,4 branch of N-glycans, is directly regulated by miR-424 in multiple mammary epithelial cell lines and observe the loss of MGAT4A in response to TGFβ, an inducer of miR-424. 26589799 1 7 theme many 168:171 arg1 processes 182:190 many cellular processes 168:190 many cellular processes 168:190 MicroRNA regulation of protein expression plays an important role in mediating many cellular processes, from cell proliferation to cell death. 26589799 5 8 theme mammary 773:779 arg1 lines 797:801 multiple mammary epithelial cell lines 764:801 multiple mammary epithelial cell lines 764:801 We demonstrate that MGAT4A, an N-acetylglucosaminyltransferase that installs the β-1,4 branch of N-glycans, is directly regulated by miR-424 in multiple mammary epithelial cell lines and observe the loss of MGAT4A in response to TGFβ, an inducer of miR-424. 26589799 7 9 theme gross 1087:1091 arg1 changes 1093:1099 gross changes 1087:1099 gross changes in overall N-linked glycosylation 1087:1133 MGAT4A does not affect levels of β-1,6 branched N-glycans, arguing that this effect is specific to β-1,4 branching and not due to gross changes in overall N-linked glycosylation. 26589799 3 10 theme glycosylation 517:529 arg1 enzymes 531:537 glycosylation enzymes 517:537 glycosylation enzymes (glycogenes) 517:550 Our laboratory recently established that microRNA can be used as a proxy to identify biological roles of glycosylation enzymes (glycogenes). 26589799 3 10 theme glycosylation 517:529 arg1 glycogenes 540:549 glycogenes 540:549 glycogenes 540:549 Our laboratory recently established that microRNA can be used as a proxy to identify biological roles of glycosylation enzymes (glycogenes). 26589799 1 11 theme cellular 173:180 arg1 processes 182:190 many cellular processes 168:190 many cellular processes 168:190 MicroRNA regulation of protein expression plays an important role in mediating many cellular processes, from cell proliferation to cell death. 26589799 5 12 theme epithelial 781:790 arg1 lines 797:801 multiple mammary epithelial cell lines 764:801 multiple mammary epithelial cell lines 764:801 We demonstrate that MGAT4A, an N-acetylglucosaminyltransferase that installs the β-1,4 branch of N-glycans, is directly regulated by miR-424 in multiple mammary epithelial cell lines and observe the loss of MGAT4A in response to TGFβ, an inducer of miR-424. 26589799 6 13 theme cycle 911:915 arg1 arrest 917:922 cell cycle arrest 906:922 cell cycle arrest 906:922 Knockdown of MGAT4A induces cell cycle arrest through decreasing CCND1 levels. 26589799 7 14 theme N-linked 1112:1119 arg1 glycosylation 1121:1133 overall N-linked glycosylation 1104:1133 overall N-linked glycosylation 1104:1133 MGAT4A does not affect levels of β-1,6 branched N-glycans, arguing that this effect is specific to β-1,4 branching and not due to gross changes in overall N-linked glycosylation. 26589799 8 15 theme progression 1197:1207 arg1 regulation 1172:1181 the regulation 1168:1181 the regulation of cell cycle progression by specific N-glycan branching patterns 1168:1247 This work provides insight into the regulation of cell cycle progression by specific N-glycan branching patterns. 26589799 5 16 theme cell 792:795 arg1 lines 797:801 multiple mammary epithelial cell lines 764:801 multiple mammary epithelial cell lines 764:801 We demonstrate that MGAT4A, an N-acetylglucosaminyltransferase that installs the β-1,4 branch of N-glycans, is directly regulated by miR-424 in multiple mammary epithelial cell lines and observe the loss of MGAT4A in response to TGFβ, an inducer of miR-424. 26589799 8 17 theme cell 1186:1189 arg1 progression 1197:1207 cell cycle progression 1186:1207 cell cycle progression 1186:1207 This work provides insight into the regulation of cell cycle progression by specific N-glycan branching patterns. 26589799 1 18 theme MicroRNA 89:96 arg1 regulation 98:107 MicroRNA regulation 89:107 MicroRNA regulation of protein expression 89:129 MicroRNA regulation of protein expression plays an important role in mediating many cellular processes, from cell proliferation to cell death. 26589799 8 19 theme cycle 1191:1195 arg1 progression 1197:1207 cell cycle progression 1186:1207 cell cycle progression 1186:1207 This work provides insight into the regulation of cell cycle progression by specific N-glycan branching patterns. 26589799 7 20 link N-linked 1112:1119 arg1 glycosylation 1121:1133 overall N-linked glycosylation 1104:1133 overall N-linked glycosylation 1104:1133 MGAT4A does not affect levels of β-1,6 branched N-glycans, arguing that this effect is specific to β-1,4 branching and not due to gross changes in overall N-linked glycosylation. 26589799 5 21 dep TGFβ 849:852 arg1 response 837:844 response 837:844 response 837:844 We demonstrate that MGAT4A, an N-acetylglucosaminyltransferase that installs the β-1,4 branch of N-glycans, is directly regulated by miR-424 in multiple mammary epithelial cell lines and observe the loss of MGAT4A in response to TGFβ, an inducer of miR-424. 26589799 8 22 theme specific 1212:1219 arg1 patterns 1240:1247 specific N-glycan branching patterns 1212:1247 specific N-glycan branching patterns 1212:1247 This work provides insight into the regulation of cell cycle progression by specific N-glycan branching patterns. 26589799 5 23 theme miR-424 869:875 arg1 TGFβ 849:852 TGFβ 849:852 TGFβ 849:852 We demonstrate that MGAT4A, an N-acetylglucosaminyltransferase that installs the β-1,4 branch of N-glycans, is directly regulated by miR-424 in multiple mammary epithelial cell lines and observe the loss of MGAT4A in response to TGFβ, an inducer of miR-424. 26589799 5 23 theme miR-424 869:875 arg1 inducer 858:864 an inducer 855:864 an inducer of miR-424 855:875 We demonstrate that MGAT4A, an N-acetylglucosaminyltransferase that installs the β-1,4 branch of N-glycans, is directly regulated by miR-424 in multiple mammary epithelial cell lines and observe the loss of MGAT4A in response to TGFβ, an inducer of miR-424. 26589799 2 24 theme anti-proliferative 290:307 arg1 cytokines 309:317 anti-proliferative cytokines 290:317 anti-proliferative cytokines 290:317 The human microRNA miR-424 is up-regulated in response to anti-proliferative cytokines, such as transforming growth factor β (TGFβ), and directly represses cell cycle progression. 26589799 2 24 theme anti-proliferative 290:307 arg1 factor 348:353 transforming growth factor β 328:355 transforming growth factor β (TGFβ) 328:362 The human microRNA miR-424 is up-regulated in response to anti-proliferative cytokines, such as transforming growth factor β (TGFβ), and directly represses cell cycle progression. 26589799 1 25 theme cell 198:201 arg1 proliferation 203:215 cell proliferation 198:215 cell proliferation 198:215 MicroRNA regulation of protein expression plays an important role in mediating many cellular processes, from cell proliferation to cell death. 26589799 0 26 theme β-1,4 33:37 arg1 Glycosylation 48:60 β-1,4 Branched Glycosylation 33:60 β-1,4 Branched Glycosylation 33:60 MicroRNA-424 Predicts a Role for β-1,4 Branched Glycosylation in Cell Cycle Progression. 26589799 2 27 theme growth 341:346 arg1 factor 348:353 transforming growth factor β 328:355 transforming growth factor β (TGFβ) 328:362 The human microRNA miR-424 is up-regulated in response to anti-proliferative cytokines, such as transforming growth factor β (TGFβ), and directly represses cell cycle progression. 26589799 2 27 theme growth 341:346 arg1 TGFβ 358:361 TGFβ 358:361 TGFβ 358:361 The human microRNA miR-424 is up-regulated in response to anti-proliferative cytokines, such as transforming growth factor β (TGFβ), and directly represses cell cycle progression. 26589799 4 28 theme miR-424 611:617 arg1 MGAT4A 572:577 MGAT4A 572:577 MGAT4A 572:577 Herein we identify MGAT4A, OGT, and GALNT13 as targets of miR-424. 26589799 4 28 theme miR-424 611:617 arg1 targets 600:606 targets 600:606 targets of miR-424 600:617 Herein we identify MGAT4A, OGT, and GALNT13 as targets of miR-424. 26589799 4 28 theme miR-424 611:617 arg1 OGT 580:582 OGT 580:582 OGT 580:582 Herein we identify MGAT4A, OGT, and GALNT13 as targets of miR-424. 26589799 4 28 theme miR-424 611:617 arg1 GALNT13 589:595 GALNT13 589:595 GALNT13 589:595 Herein we identify MGAT4A, OGT, and GALNT13 as targets of miR-424. 26589799 2 29 theme cycle 393:397 arg1 progression 399:409 cell cycle progression 388:409 cell cycle progression 388:409 The human microRNA miR-424 is up-regulated in response to anti-proliferative cytokines, such as transforming growth factor β (TGFβ), and directly represses cell cycle progression. 26589799 5 30 theme MGAT4A 827:832 arg1 loss 819:822 the loss 815:822 the loss of MGAT4A 815:832 We demonstrate that MGAT4A, an N-acetylglucosaminyltransferase that installs the β-1,4 branch of N-glycans, is directly regulated by miR-424 in multiple mammary epithelial cell lines and observe the loss of MGAT4A in response to TGFβ, an inducer of miR-424. 26589799 6 31 theme cell 906:909 arg1 arrest 917:922 cell cycle arrest 906:922 cell cycle arrest 906:922 Knockdown of MGAT4A induces cell cycle arrest through decreasing CCND1 levels. 26589799 5 32 theme β-1,4 701:705 arg1 branch 707:712 the β-1,4 branch 697:712 the β-1,4 branch of N-glycans 697:725 We demonstrate that MGAT4A, an N-acetylglucosaminyltransferase that installs the β-1,4 branch of N-glycans, is directly regulated by miR-424 in multiple mammary epithelial cell lines and observe the loss of MGAT4A in response to TGFβ, an inducer of miR-424. 26589799 8 33 theme branching 1230:1238 arg1 patterns 1240:1247 specific N-glycan branching patterns 1212:1247 specific N-glycan branching patterns 1212:1247 This work provides insight into the regulation of cell cycle progression by specific N-glycan branching patterns. 26589799 3 34 used used 469:472 arg2 microRNA 453:460 microRNA 453:460 microRNA 453:460 Our laboratory recently established that microRNA can be used as a proxy to identify biological roles of glycosylation enzymes (glycogenes). 26589799 3 34 used used 469:472 arg2 proxy 479:483 a proxy 477:483 a proxy to identify biological roles of glycosylation enzymes (glycogenes) 477:550 Our laboratory recently established that microRNA can be used as a proxy to identify biological roles of glycosylation enzymes (glycogenes). 26589799 2 35 theme cell 388:391 arg1 progression 399:409 cell cycle progression 388:409 cell cycle progression 388:409 The human microRNA miR-424 is up-regulated in response to anti-proliferative cytokines, such as transforming growth factor β (TGFβ), and directly represses cell cycle progression. 26589799 5 36 theme multiple 764:771 arg1 lines 797:801 multiple mammary epithelial cell lines 764:801 multiple mammary epithelial cell lines 764:801 We demonstrate that MGAT4A, an N-acetylglucosaminyltransferase that installs the β-1,4 branch of N-glycans, is directly regulated by miR-424 in multiple mammary epithelial cell lines and observe the loss of MGAT4A in response to TGFβ, an inducer of miR-424. 26589799 7 37 theme branched 996:1003 arg1 N-glycans 1005:1013 β-1,6 branched N-glycans 990:1013 β-1,6 branched N-glycans 990:1013 MGAT4A does not affect levels of β-1,6 branched N-glycans, arguing that this effect is specific to β-1,4 branching and not due to gross changes in overall N-linked glycosylation. 26589799 1 38 theme protein 112:118 arg1 expression 120:129 protein expression 112:129 protein expression 112:129 MicroRNA regulation of protein expression plays an important role in mediating many cellular processes, from cell proliferation to cell death. 26589799 0 39 theme Branched 39:46 arg1 Glycosylation 48:60 β-1,4 Branched Glycosylation 33:60 β-1,4 Branched Glycosylation 33:60 MicroRNA-424 Predicts a Role for β-1,4 Branched Glycosylation in Cell Cycle Progression. 26589799 6 40 theme MGAT4A 891:896 arg1 Knockdown 878:886 Knockdown 878:886 Knockdown of MGAT4A 878:896 Knockdown of MGAT4A induces cell cycle arrest through decreasing CCND1 levels. 26589799 7 41 theme N-glycans 1005:1013 arg1 levels 980:985 levels 980:985 levels of β-1,6 branched N-glycans 980:1013 MGAT4A does not affect levels of β-1,6 branched N-glycans, arguing that this effect is specific to β-1,4 branching and not due to gross changes in overall N-linked glycosylation. 26589799 1 42 theme expression 120:129 arg1 regulation 98:107 MicroRNA regulation 89:107 MicroRNA regulation of protein expression 89:129 MicroRNA regulation of protein expression plays an important role in mediating many cellular processes, from cell proliferation to cell death. 26589799 2 43 theme transforming 328:339 arg1 factor 348:353 transforming growth factor β 328:355 transforming growth factor β (TGFβ) 328:362 The human microRNA miR-424 is up-regulated in response to anti-proliferative cytokines, such as transforming growth factor β (TGFβ), and directly represses cell cycle progression. 26589799 2 43 theme transforming 328:339 arg1 TGFβ 358:361 TGFβ 358:361 TGFβ 358:361 The human microRNA miR-424 is up-regulated in response to anti-proliferative cytokines, such as transforming growth factor β (TGFβ), and directly represses cell cycle progression. 26589799 1 44 theme cell 220:223 arg1 death 225:229 cell death 220:229 cell death 220:229 MicroRNA regulation of protein expression plays an important role in mediating many cellular processes, from cell proliferation to cell death. 26589799 7 45 theme β-1,6 990:994 arg1 N-glycans 1005:1013 β-1,6 branched N-glycans 990:1013 β-1,6 branched N-glycans 990:1013 MGAT4A does not affect levels of β-1,6 branched N-glycans, arguing that this effect is specific to β-1,4 branching and not due to gross changes in overall N-linked glycosylation. 26589799 0 46 theme Cell 65:68 arg1 Progression 76:86 Cell Cycle Progression 65:86 Cell Cycle Progression 65:86 MicroRNA-424 Predicts a Role for β-1,4 Branched Glycosylation in Cell Cycle Progression. 26589799 8 47 theme N-glycan 1221:1228 arg1 patterns 1240:1247 specific N-glycan branching patterns 1212:1247 specific N-glycan branching patterns 1212:1247 This work provides insight into the regulation of cell cycle progression by specific N-glycan branching patterns. 26589799 2 48 theme microRNA 242:249 arg1 miR-424 251:257 The human microRNA miR-424 232:257 The human microRNA miR-424 232:257 The human microRNA miR-424 is up-regulated in response to anti-proliferative cytokines, such as transforming growth factor β (TGFβ), and directly represses cell cycle progression. 26589799 1 49 theme important 140:148 arg1 role 150:153 an important role 137:153 an important role 137:153 MicroRNA regulation of protein expression plays an important role in mediating many cellular processes, from cell proliferation to cell death. 26589799 7 50 dep specific 1044:1051 arg1 due 1080:1082 due 1080:1082 due 1080:1082 MGAT4A does not affect levels of β-1,6 branched N-glycans, arguing that this effect is specific to β-1,4 branching and not due to gross changes in overall N-linked glycosylation. 26589799 0 51 from Role 24:27 arg1 Progression 76:86 Cell Cycle Progression 65:86 Cell Cycle Progression 65:86 MicroRNA-424 Predicts a Role for β-1,4 Branched Glycosylation in Cell Cycle Progression. 26589799 2 52 theme human 236:240 arg1 miR-424 251:257 The human microRNA miR-424 232:257 The human microRNA miR-424 232:257 The human microRNA miR-424 is up-regulated in response to anti-proliferative cytokines, such as transforming growth factor β (TGFβ), and directly represses cell cycle progression. 26589799 7 53 theme overall 1104:1110 arg1 glycosylation 1121:1133 overall N-linked glycosylation 1104:1133 overall N-linked glycosylation 1104:1133 MGAT4A does not affect levels of β-1,6 branched N-glycans, arguing that this effect is specific to β-1,4 branching and not due to gross changes in overall N-linked glycosylation. 26637370 4 0 with interference 755:766 arg1 glycosylation 782:794 N-linked glycosylation 773:794 N-linked glycosylation 773:794 Downregulation of these critical survival pathways is shown to be due to 2-DG's interference with N-linked glycosylation, leading to alterations in VEGFR2 (and downstream signaling) as well as induction of endoplasmic reticulum (ER) stress, GSK3β activation, and apoptosis. 26637370 1 1 with Interference 165:176 arg1 metabolism 200:209 endothelial cell metabolism 183:209 endothelial cell metabolism 183:209 Interference with endothelial cell metabolism is a promising, yet unexploited strategy for angiogenesis inhibition. 26637370 6 2 theme endothelial 1269:1279 arg1 cells 1281:1285 endothelial cells 1269:1285 endothelial cells 1269:1285 These findings uniquely link N-linked glycosylation inhibition, ER stress, and ERK/AKT downregulation in endothelial cells, and provide a novel drug development strategy to overcome resistance mechanisms to currently available antiangiogenic agents. 26637370 3 3 theme enhanced 537:544 arg1 uptake 551:556 enhanced drug uptake 537:556 enhanced drug uptake compared with tumor cells 537:582 Here, we found that hypersensitivity to 2-DG in endothelial cells is not associated with enhanced drug uptake compared with tumor cells, but with time-dependent, endothelial-selective inhibition of AKT and ERK phosphorylation. 26637370 5 4 theme GRP 1109:1111 arg1 stress 1101:1106 ER stress 1098:1106 ER stress (GRP 78 expression) 1098:1126 In vivo, periocular administration of 2-DG in LHBETATAG mice was associated with significant reduction of newly formed (CD105(+)) tumor capillaries, ER stress (GRP 78 expression), and endothelial apoptosis (TUNEL). 26637370 5 4 theme GRP 1109:1111 arg1 expression 1116:1125 GRP 78 expression 1109:1125 GRP 78 expression 1109:1125 In vivo, periocular administration of 2-DG in LHBETATAG mice was associated with significant reduction of newly formed (CD105(+)) tumor capillaries, ER stress (GRP 78 expression), and endothelial apoptosis (TUNEL). 26637370 6 5 theme ER 1228:1229 arg1 stress 1231:1236 ER stress 1228:1236 ER stress 1228:1236 These findings uniquely link N-linked glycosylation inhibition, ER stress, and ERK/AKT downregulation in endothelial cells, and provide a novel drug development strategy to overcome resistance mechanisms to currently available antiangiogenic agents. 26637370 3 6 theme drug 546:549 arg1 uptake 551:556 enhanced drug uptake 537:556 enhanced drug uptake compared with tumor cells 537:582 Here, we found that hypersensitivity to 2-DG in endothelial cells is not associated with enhanced drug uptake compared with tumor cells, but with time-dependent, endothelial-selective inhibition of AKT and ERK phosphorylation. 26637370 5 7 theme LHBETATAG 995:1003 arg1 mice 1005:1008 LHBETATAG mice 995:1008 LHBETATAG mice 995:1008 In vivo, periocular administration of 2-DG in LHBETATAG mice was associated with significant reduction of newly formed (CD105(+)) tumor capillaries, ER stress (GRP 78 expression), and endothelial apoptosis (TUNEL). 26637370 4 8 theme stress 908:913 arg1 alterations 808:818 alterations 808:818 alterations in VEGFR2 (and downstream signaling) as well as induction of endoplasmic reticulum (ER) stress, GSK3β activation, and apoptosis 808:946 Downregulation of these critical survival pathways is shown to be due to 2-DG's interference with N-linked glycosylation, leading to alterations in VEGFR2 (and downstream signaling) as well as induction of endoplasmic reticulum (ER) stress, GSK3β activation, and apoptosis. 26637370 4 8 theme stress 908:913 arg1 induction 868:876 induction 868:876 alterations in VEGFR2 (and downstream signaling) as well as induction of endoplasmic reticulum (ER) stress, GSK3β activation, and apoptosis 808:946 Downregulation of these critical survival pathways is shown to be due to 2-DG's interference with N-linked glycosylation, leading to alterations in VEGFR2 (and downstream signaling) as well as induction of endoplasmic reticulum (ER) stress, GSK3β activation, and apoptosis. 26637370 2 9 theme analogue 310:317 arg1 2-DG 338:341 2-DG 338:341 2-DG 338:341 We reported that the glucose analogue 2-deoxy-D-glucose (2-DG) inhibits angiogenesis at significantly lower concentrations than those required for tumor cytotoxicity. 26637370 2 9 theme analogue 310:317 arg1 2-deoxy-D-glucose 319:335 the glucose analogue 2-deoxy-D-glucose 298:335 the glucose analogue 2-deoxy-D-glucose (2-DG) 298:342 We reported that the glucose analogue 2-deoxy-D-glucose (2-DG) inhibits angiogenesis at significantly lower concentrations than those required for tumor cytotoxicity. 26637370 0 10 with Activation 153:162 arg1 Glycosylation 85:97 N-Linked Glycosylation 76:97 N-Linked Glycosylation 76:97 2-Deoxy-Glucose Downregulates Endothelial AKT and ERK via Interference with N-Linked Glycosylation, Induction of Endoplasmic Reticulum Stress, and GSK3β Activation. 26637370 5 11 dep formed 1061:1066 arg1 CD105 1069:1073 CD105 1069:1073 CD105 1069:1073 In vivo, periocular administration of 2-DG in LHBETATAG mice was associated with significant reduction of newly formed (CD105(+)) tumor capillaries, ER stress (GRP 78 expression), and endothelial apoptosis (TUNEL). 26637370 4 12 gly glycosylation 782:794 arg1 interference 755:766 2-DG's interference 748:766 2-DG's interference with N-linked glycosylation 748:794 Downregulation of these critical survival pathways is shown to be due to 2-DG's interference with N-linked glycosylation, leading to alterations in VEGFR2 (and downstream signaling) as well as induction of endoplasmic reticulum (ER) stress, GSK3β activation, and apoptosis. 26637370 5 13 theme capillaries 1085:1095 arg1 reduction 1042:1050 significant reduction 1030:1050 significant reduction of newly formed (CD105(+)) tumor capillaries 1030:1095 In vivo, periocular administration of 2-DG in LHBETATAG mice was associated with significant reduction of newly formed (CD105(+)) tumor capillaries, ER stress (GRP 78 expression), and endothelial apoptosis (TUNEL). 26637370 5 13 theme capillaries 1085:1095 arg1 stress 1101:1106 ER stress 1098:1106 ER stress (GRP 78 expression) 1098:1126 In vivo, periocular administration of 2-DG in LHBETATAG mice was associated with significant reduction of newly formed (CD105(+)) tumor capillaries, ER stress (GRP 78 expression), and endothelial apoptosis (TUNEL). 26637370 5 13 theme capillaries 1085:1095 arg1 TUNEL 1156:1160 TUNEL 1156:1160 TUNEL 1156:1160 In vivo, periocular administration of 2-DG in LHBETATAG mice was associated with significant reduction of newly formed (CD105(+)) tumor capillaries, ER stress (GRP 78 expression), and endothelial apoptosis (TUNEL). 26637370 5 13 theme capillaries 1085:1095 arg1 apoptosis 1145:1153 endothelial apoptosis 1133:1153 endothelial apoptosis (TUNEL) 1133:1161 In vivo, periocular administration of 2-DG in LHBETATAG mice was associated with significant reduction of newly formed (CD105(+)) tumor capillaries, ER stress (GRP 78 expression), and endothelial apoptosis (TUNEL). 26637370 5 13 theme capillaries 1085:1095 arg1 expression 1116:1125 GRP 78 expression 1109:1125 GRP 78 expression 1109:1125 In vivo, periocular administration of 2-DG in LHBETATAG mice was associated with significant reduction of newly formed (CD105(+)) tumor capillaries, ER stress (GRP 78 expression), and endothelial apoptosis (TUNEL). 26637370 5 14 theme 2-DG 987:990 arg1 administration 969:982 periocular administration 958:982 periocular administration of 2-DG in LHBETATAG mice 958:1008 In vivo, periocular administration of 2-DG in LHBETATAG mice was associated with significant reduction of newly formed (CD105(+)) tumor capillaries, ER stress (GRP 78 expression), and endothelial apoptosis (TUNEL). 26637370 4 15 from alterations 808:818 arg1 signaling 846:854 downstream signaling 835:854 downstream signaling 835:854 Downregulation of these critical survival pathways is shown to be due to 2-DG's interference with N-linked glycosylation, leading to alterations in VEGFR2 (and downstream signaling) as well as induction of endoplasmic reticulum (ER) stress, GSK3β activation, and apoptosis. 26637370 4 15 from alterations 808:818 arg1 VEGFR2 823:828 VEGFR2 823:828 VEGFR2 823:828 Downregulation of these critical survival pathways is shown to be due to 2-DG's interference with N-linked glycosylation, leading to alterations in VEGFR2 (and downstream signaling) as well as induction of endoplasmic reticulum (ER) stress, GSK3β activation, and apoptosis. 26637370 2 16 theme glucose 302:308 arg1 2-DG 338:341 2-DG 338:341 2-DG 338:341 We reported that the glucose analogue 2-deoxy-D-glucose (2-DG) inhibits angiogenesis at significantly lower concentrations than those required for tumor cytotoxicity. 26637370 2 16 theme glucose 302:308 arg1 2-deoxy-D-glucose 319:335 the glucose analogue 2-deoxy-D-glucose 298:335 the glucose analogue 2-deoxy-D-glucose (2-DG) 298:342 We reported that the glucose analogue 2-deoxy-D-glucose (2-DG) inhibits angiogenesis at significantly lower concentrations than those required for tumor cytotoxicity. 26637370 0 17 theme Reticulum 125:133 arg1 Stress 135:140 Endoplasmic Reticulum Stress 113:140 Endoplasmic Reticulum Stress 113:140 2-Deoxy-Glucose Downregulates Endothelial AKT and ERK via Interference with N-Linked Glycosylation, Induction of Endoplasmic Reticulum Stress, and GSK3β Activation. 26637370 4 18 link N-linked 773:780 arg1 glycosylation 782:794 N-linked glycosylation 773:794 N-linked glycosylation 773:794 Downregulation of these critical survival pathways is shown to be due to 2-DG's interference with N-linked glycosylation, leading to alterations in VEGFR2 (and downstream signaling) as well as induction of endoplasmic reticulum (ER) stress, GSK3β activation, and apoptosis. 26637370 1 19 theme endothelial 183:193 arg1 metabolism 200:209 endothelial cell metabolism 183:209 endothelial cell metabolism 183:209 Interference with endothelial cell metabolism is a promising, yet unexploited strategy for angiogenesis inhibition. 26637370 0 20 theme Endoplasmic 113:123 arg1 Reticulum 125:133 Endoplasmic Reticulum 113:133 Endoplasmic Reticulum Stress 113:140 2-Deoxy-Glucose Downregulates Endothelial AKT and ERK via Interference with N-Linked Glycosylation, Induction of Endoplasmic Reticulum Stress, and GSK3β Activation. 26637370 5 21 theme ER 1098:1099 arg1 stress 1101:1106 ER stress 1098:1106 ER stress (GRP 78 expression) 1098:1126 In vivo, periocular administration of 2-DG in LHBETATAG mice was associated with significant reduction of newly formed (CD105(+)) tumor capillaries, ER stress (GRP 78 expression), and endothelial apoptosis (TUNEL). 26637370 5 21 theme ER 1098:1099 arg1 expression 1116:1125 GRP 78 expression 1109:1125 GRP 78 expression 1109:1125 In vivo, periocular administration of 2-DG in LHBETATAG mice was associated with significant reduction of newly formed (CD105(+)) tumor capillaries, ER stress (GRP 78 expression), and endothelial apoptosis (TUNEL). 26637370 6 22 theme development 1313:1323 arg1 strategy 1325:1332 a novel drug development strategy 1300:1332 a novel drug development strategy to overcome resistance mechanisms to currently available antiangiogenic agents 1300:1411 These findings uniquely link N-linked glycosylation inhibition, ER stress, and ERK/AKT downregulation in endothelial cells, and provide a novel drug development strategy to overcome resistance mechanisms to currently available antiangiogenic agents. 26637370 3 23 theme tumor 572:576 arg1 cells 578:582 tumor cells 572:582 tumor cells 572:582 Here, we found that hypersensitivity to 2-DG in endothelial cells is not associated with enhanced drug uptake compared with tumor cells, but with time-dependent, endothelial-selective inhibition of AKT and ERK phosphorylation. 26637370 5 24 from mice 1005:1008 arg1 administration 969:982 periocular administration 958:982 periocular administration of 2-DG in LHBETATAG mice 958:1008 In vivo, periocular administration of 2-DG in LHBETATAG mice was associated with significant reduction of newly formed (CD105(+)) tumor capillaries, ER stress (GRP 78 expression), and endothelial apoptosis (TUNEL). 26637370 1 25 theme cell 195:198 arg1 metabolism 200:209 endothelial cell metabolism 183:209 endothelial cell metabolism 183:209 Interference with endothelial cell metabolism is a promising, yet unexploited strategy for angiogenesis inhibition. 26637370 3 26 dep time-dependent 594:607 arg1 endothelial-selective 610:630 endothelial-selective 610:630 endothelial-selective 610:630 Here, we found that hypersensitivity to 2-DG in endothelial cells is not associated with enhanced drug uptake compared with tumor cells, but with time-dependent, endothelial-selective inhibition of AKT and ERK phosphorylation. 26637370 4 27 from induction 868:876 arg1 signaling 846:854 downstream signaling 835:854 downstream signaling 835:854 Downregulation of these critical survival pathways is shown to be due to 2-DG's interference with N-linked glycosylation, leading to alterations in VEGFR2 (and downstream signaling) as well as induction of endoplasmic reticulum (ER) stress, GSK3β activation, and apoptosis. 26637370 4 27 from induction 868:876 arg1 VEGFR2 823:828 VEGFR2 823:828 VEGFR2 823:828 Downregulation of these critical survival pathways is shown to be due to 2-DG's interference with N-linked glycosylation, leading to alterations in VEGFR2 (and downstream signaling) as well as induction of endoplasmic reticulum (ER) stress, GSK3β activation, and apoptosis. 26637370 4 28 theme reticulum 893:901 arg1 stress 908:913 endoplasmic reticulum (ER) stress 881:913 endoplasmic reticulum (ER) stress 881:913 Downregulation of these critical survival pathways is shown to be due to 2-DG's interference with N-linked glycosylation, leading to alterations in VEGFR2 (and downstream signaling) as well as induction of endoplasmic reticulum (ER) stress, GSK3β activation, and apoptosis. 26637370 4 29 theme survival 708:715 arg1 pathways 717:724 these critical survival pathways 693:724 these critical survival pathways 693:724 Downregulation of these critical survival pathways is shown to be due to 2-DG's interference with N-linked glycosylation, leading to alterations in VEGFR2 (and downstream signaling) as well as induction of endoplasmic reticulum (ER) stress, GSK3β activation, and apoptosis. 26637370 3 30 theme time-dependent 594:607 arg1 inhibition 632:641 time-dependent, endothelial-selective inhibition 594:641 time-dependent, endothelial-selective inhibition of AKT and ERK phosphorylation 594:672 Here, we found that hypersensitivity to 2-DG in endothelial cells is not associated with enhanced drug uptake compared with tumor cells, but with time-dependent, endothelial-selective inhibition of AKT and ERK phosphorylation. 26637370 6 31 link N-linked 1193:1200 arg1 inhibition 1216:1225 N-linked glycosylation inhibition 1193:1225 N-linked glycosylation inhibition 1193:1225 These findings uniquely link N-linked glycosylation inhibition, ER stress, and ERK/AKT downregulation in endothelial cells, and provide a novel drug development strategy to overcome resistance mechanisms to currently available antiangiogenic agents. 26637370 4 32 theme endoplasmic 881:891 arg1 ER 904:905 ER 904:905 ER 904:905 Downregulation of these critical survival pathways is shown to be due to 2-DG's interference with N-linked glycosylation, leading to alterations in VEGFR2 (and downstream signaling) as well as induction of endoplasmic reticulum (ER) stress, GSK3β activation, and apoptosis. 26637370 4 32 theme endoplasmic 881:891 arg1 reticulum 893:901 endoplasmic reticulum 881:901 endoplasmic reticulum (ER) stress 881:913 Downregulation of these critical survival pathways is shown to be due to 2-DG's interference with N-linked glycosylation, leading to alterations in VEGFR2 (and downstream signaling) as well as induction of endoplasmic reticulum (ER) stress, GSK3β activation, and apoptosis. 26637370 4 33 theme N-linked 773:780 arg1 glycosylation 782:794 N-linked glycosylation 773:794 N-linked glycosylation 773:794 Downregulation of these critical survival pathways is shown to be due to 2-DG's interference with N-linked glycosylation, leading to alterations in VEGFR2 (and downstream signaling) as well as induction of endoplasmic reticulum (ER) stress, GSK3β activation, and apoptosis. 26637370 6 34 theme novel 1302:1306 arg1 strategy 1325:1332 a novel drug development strategy 1300:1332 a novel drug development strategy to overcome resistance mechanisms to currently available antiangiogenic agents 1300:1411 These findings uniquely link N-linked glycosylation inhibition, ER stress, and ERK/AKT downregulation in endothelial cells, and provide a novel drug development strategy to overcome resistance mechanisms to currently available antiangiogenic agents. 26637370 4 35 theme apoptosis 938:946 arg1 alterations 808:818 alterations 808:818 alterations in VEGFR2 (and downstream signaling) as well as induction of endoplasmic reticulum (ER) stress, GSK3β activation, and apoptosis 808:946 Downregulation of these critical survival pathways is shown to be due to 2-DG's interference with N-linked glycosylation, leading to alterations in VEGFR2 (and downstream signaling) as well as induction of endoplasmic reticulum (ER) stress, GSK3β activation, and apoptosis. 26637370 4 35 theme apoptosis 938:946 arg1 induction 868:876 induction 868:876 alterations in VEGFR2 (and downstream signaling) as well as induction of endoplasmic reticulum (ER) stress, GSK3β activation, and apoptosis 808:946 Downregulation of these critical survival pathways is shown to be due to 2-DG's interference with N-linked glycosylation, leading to alterations in VEGFR2 (and downstream signaling) as well as induction of endoplasmic reticulum (ER) stress, GSK3β activation, and apoptosis. 26637370 0 36 with Induction 100:108 arg1 Glycosylation 85:97 N-Linked Glycosylation 76:97 N-Linked Glycosylation 76:97 2-Deoxy-Glucose Downregulates Endothelial AKT and ERK via Interference with N-Linked Glycosylation, Induction of Endoplasmic Reticulum Stress, and GSK3β Activation. 26637370 5 37 theme periocular 958:967 arg1 administration 969:982 periocular administration 958:982 periocular administration of 2-DG in LHBETATAG mice 958:1008 In vivo, periocular administration of 2-DG in LHBETATAG mice was associated with significant reduction of newly formed (CD105(+)) tumor capillaries, ER stress (GRP 78 expression), and endothelial apoptosis (TUNEL). 26637370 3 38 theme endothelial 496:506 arg1 cells 508:512 endothelial cells 496:512 endothelial cells 496:512 Here, we found that hypersensitivity to 2-DG in endothelial cells is not associated with enhanced drug uptake compared with tumor cells, but with time-dependent, endothelial-selective inhibition of AKT and ERK phosphorylation. 26637370 0 39 theme Endothelial 30:40 arg1 AKT 42:44 Endothelial AKT 30:44 Endothelial AKT 30:44 2-Deoxy-Glucose Downregulates Endothelial AKT and ERK via Interference with N-Linked Glycosylation, Induction of Endoplasmic Reticulum Stress, and GSK3β Activation. 26637370 0 40 theme Stress 135:140 arg1 Activation 153:162 GSK3β Activation 147:162 GSK3β Activation 147:162 2-Deoxy-Glucose Downregulates Endothelial AKT and ERK via Interference with N-Linked Glycosylation, Induction of Endoplasmic Reticulum Stress, and GSK3β Activation. 26637370 0 40 theme Stress 135:140 arg1 Induction 100:108 Induction 100:108 Induction of Endoplasmic Reticulum Stress 100:140 2-Deoxy-Glucose Downregulates Endothelial AKT and ERK via Interference with N-Linked Glycosylation, Induction of Endoplasmic Reticulum Stress, and GSK3β Activation. 26637370 0 40 theme Stress 135:140 arg1 Interference 58:69 Interference 58:69 Interference with N-Linked Glycosylation 58:97 2-Deoxy-Glucose Downregulates Endothelial AKT and ERK via Interference with N-Linked Glycosylation, Induction of Endoplasmic Reticulum Stress, and GSK3β Activation. 26637370 2 41 theme lower 383:387 arg1 concentrations 389:402 significantly lower concentrations 369:402 significantly lower concentrations than those required for tumor cytotoxicity 369:445 We reported that the glucose analogue 2-deoxy-D-glucose (2-DG) inhibits angiogenesis at significantly lower concentrations than those required for tumor cytotoxicity. 26637370 1 42 theme promising 216:224 arg1 Interference 165:176 Interference 165:176 Interference with endothelial cell metabolism 165:209 Interference with endothelial cell metabolism is a promising, yet unexploited strategy for angiogenesis inhibition. 26637370 1 42 theme promising 216:224 arg1 strategy 243:250 a promising, yet unexploited strategy 214:250 a promising, yet unexploited strategy for angiogenesis inhibition 214:278 Interference with endothelial cell metabolism is a promising, yet unexploited strategy for angiogenesis inhibition. 26637370 0 43 theme GSK3β 147:151 arg1 Activation 153:162 GSK3β Activation 147:162 GSK3β Activation 147:162 2-Deoxy-Glucose Downregulates Endothelial AKT and ERK via Interference with N-Linked Glycosylation, Induction of Endoplasmic Reticulum Stress, and GSK3β Activation. 26637370 5 44 theme significant 1030:1040 arg1 reduction 1042:1050 significant reduction 1030:1050 significant reduction of newly formed (CD105(+)) tumor capillaries 1030:1095 In vivo, periocular administration of 2-DG in LHBETATAG mice was associated with significant reduction of newly formed (CD105(+)) tumor capillaries, ER stress (GRP 78 expression), and endothelial apoptosis (TUNEL). 26637370 4 45 theme critical 699:706 arg1 pathways 717:724 these critical survival pathways 693:724 these critical survival pathways 693:724 Downregulation of these critical survival pathways is shown to be due to 2-DG's interference with N-linked glycosylation, leading to alterations in VEGFR2 (and downstream signaling) as well as induction of endoplasmic reticulum (ER) stress, GSK3β activation, and apoptosis. 26637370 4 46 theme pathways 717:724 arg1 Downregulation 675:688 Downregulation 675:688 Downregulation of these critical survival pathways 675:724 Downregulation of these critical survival pathways is shown to be due to 2-DG's interference with N-linked glycosylation, leading to alterations in VEGFR2 (and downstream signaling) as well as induction of endoplasmic reticulum (ER) stress, GSK3β activation, and apoptosis. 26637370 3 47 theme AKT 646:648 arg1 inhibition 632:641 time-dependent, endothelial-selective inhibition 594:641 time-dependent, endothelial-selective inhibition of AKT and ERK phosphorylation 594:672 Here, we found that hypersensitivity to 2-DG in endothelial cells is not associated with enhanced drug uptake compared with tumor cells, but with time-dependent, endothelial-selective inhibition of AKT and ERK phosphorylation. 26637370 5 48 theme endothelial 1133:1143 arg1 TUNEL 1156:1160 TUNEL 1156:1160 TUNEL 1156:1160 In vivo, periocular administration of 2-DG in LHBETATAG mice was associated with significant reduction of newly formed (CD105(+)) tumor capillaries, ER stress (GRP 78 expression), and endothelial apoptosis (TUNEL). 26637370 5 48 theme endothelial 1133:1143 arg1 apoptosis 1145:1153 endothelial apoptosis 1133:1153 endothelial apoptosis (TUNEL) 1133:1161 In vivo, periocular administration of 2-DG in LHBETATAG mice was associated with significant reduction of newly formed (CD105(+)) tumor capillaries, ER stress (GRP 78 expression), and endothelial apoptosis (TUNEL). 26637370 6 49 theme antiangiogenic 1391:1404 arg1 agents 1406:1411 currently available antiangiogenic agents 1371:1411 currently available antiangiogenic agents 1371:1411 These findings uniquely link N-linked glycosylation inhibition, ER stress, and ERK/AKT downregulation in endothelial cells, and provide a novel drug development strategy to overcome resistance mechanisms to currently available antiangiogenic agents. 26637370 4 50 theme GSK3β 916:920 arg1 activation 922:931 GSK3β activation 916:931 GSK3β activation 916:931 Downregulation of these critical survival pathways is shown to be due to 2-DG's interference with N-linked glycosylation, leading to alterations in VEGFR2 (and downstream signaling) as well as induction of endoplasmic reticulum (ER) stress, GSK3β activation, and apoptosis. 26637370 5 51 theme tumor 1079:1083 arg1 capillaries 1085:1095 newly formed (CD105(+)) tumor capillaries 1055:1095 newly formed (CD105(+)) tumor capillaries 1055:1095 In vivo, periocular administration of 2-DG in LHBETATAG mice was associated with significant reduction of newly formed (CD105(+)) tumor capillaries, ER stress (GRP 78 expression), and endothelial apoptosis (TUNEL). 26637370 6 52 theme N-linked 1193:1200 arg1 inhibition 1216:1225 N-linked glycosylation inhibition 1193:1225 N-linked glycosylation inhibition 1193:1225 These findings uniquely link N-linked glycosylation inhibition, ER stress, and ERK/AKT downregulation in endothelial cells, and provide a novel drug development strategy to overcome resistance mechanisms to currently available antiangiogenic agents. 26637370 6 53 theme available 1381:1389 arg1 agents 1406:1411 currently available antiangiogenic agents 1371:1411 currently available antiangiogenic agents 1371:1411 These findings uniquely link N-linked glycosylation inhibition, ER stress, and ERK/AKT downregulation in endothelial cells, and provide a novel drug development strategy to overcome resistance mechanisms to currently available antiangiogenic agents. 26637370 6 54 theme drug 1308:1311 arg1 strategy 1325:1332 a novel drug development strategy 1300:1332 a novel drug development strategy to overcome resistance mechanisms to currently available antiangiogenic agents 1300:1411 These findings uniquely link N-linked glycosylation inhibition, ER stress, and ERK/AKT downregulation in endothelial cells, and provide a novel drug development strategy to overcome resistance mechanisms to currently available antiangiogenic agents. 26637370 5 55 theme formed 1061:1066 arg1 capillaries 1085:1095 newly formed (CD105(+)) tumor capillaries 1055:1095 newly formed (CD105(+)) tumor capillaries 1055:1095 In vivo, periocular administration of 2-DG in LHBETATAG mice was associated with significant reduction of newly formed (CD105(+)) tumor capillaries, ER stress (GRP 78 expression), and endothelial apoptosis (TUNEL). 26637370 6 56 theme ERK/AKT 1243:1249 arg1 downregulation 1251:1264 ERK/AKT downregulation 1243:1264 ERK/AKT downregulation 1243:1264 These findings uniquely link N-linked glycosylation inhibition, ER stress, and ERK/AKT downregulation in endothelial cells, and provide a novel drug development strategy to overcome resistance mechanisms to currently available antiangiogenic agents. 26637370 4 57 theme downstream 835:844 arg1 signaling 846:854 downstream signaling 835:854 downstream signaling 835:854 Downregulation of these critical survival pathways is shown to be due to 2-DG's interference with N-linked glycosylation, leading to alterations in VEGFR2 (and downstream signaling) as well as induction of endoplasmic reticulum (ER) stress, GSK3β activation, and apoptosis. 26637370 3 58 theme phosphorylation 658:672 arg1 inhibition 632:641 time-dependent, endothelial-selective inhibition 594:641 time-dependent, endothelial-selective inhibition of AKT and ERK phosphorylation 594:672 Here, we found that hypersensitivity to 2-DG in endothelial cells is not associated with enhanced drug uptake compared with tumor cells, but with time-dependent, endothelial-selective inhibition of AKT and ERK phosphorylation. 26637370 6 59 theme glycosylation 1202:1214 arg1 inhibition 1216:1225 N-linked glycosylation inhibition 1193:1225 N-linked glycosylation inhibition 1193:1225 These findings uniquely link N-linked glycosylation inhibition, ER stress, and ERK/AKT downregulation in endothelial cells, and provide a novel drug development strategy to overcome resistance mechanisms to currently available antiangiogenic agents. 26637370 5 60 from administration 969:982 arg1 mice 1005:1008 LHBETATAG mice 995:1008 LHBETATAG mice 995:1008 In vivo, periocular administration of 2-DG in LHBETATAG mice was associated with significant reduction of newly formed (CD105(+)) tumor capillaries, ER stress (GRP 78 expression), and endothelial apoptosis (TUNEL). 26637370 1 61 theme unexploited 231:241 arg1 Interference 165:176 Interference 165:176 Interference with endothelial cell metabolism 165:209 Interference with endothelial cell metabolism is a promising, yet unexploited strategy for angiogenesis inhibition. 26637370 1 61 theme unexploited 231:241 arg1 strategy 243:250 a promising, yet unexploited strategy 214:250 a promising, yet unexploited strategy for angiogenesis inhibition 214:278 Interference with endothelial cell metabolism is a promising, yet unexploited strategy for angiogenesis inhibition. 26637370 4 62 theme activation 922:931 arg1 alterations 808:818 alterations 808:818 alterations in VEGFR2 (and downstream signaling) as well as induction of endoplasmic reticulum (ER) stress, GSK3β activation, and apoptosis 808:946 Downregulation of these critical survival pathways is shown to be due to 2-DG's interference with N-linked glycosylation, leading to alterations in VEGFR2 (and downstream signaling) as well as induction of endoplasmic reticulum (ER) stress, GSK3β activation, and apoptosis. 26637370 4 62 theme activation 922:931 arg1 induction 868:876 induction 868:876 alterations in VEGFR2 (and downstream signaling) as well as induction of endoplasmic reticulum (ER) stress, GSK3β activation, and apoptosis 808:946 Downregulation of these critical survival pathways is shown to be due to 2-DG's interference with N-linked glycosylation, leading to alterations in VEGFR2 (and downstream signaling) as well as induction of endoplasmic reticulum (ER) stress, GSK3β activation, and apoptosis. 26637370 0 63 with Interference 58:69 arg1 Glycosylation 85:97 N-Linked Glycosylation 76:97 N-Linked Glycosylation 76:97 2-Deoxy-Glucose Downregulates Endothelial AKT and ERK via Interference with N-Linked Glycosylation, Induction of Endoplasmic Reticulum Stress, and GSK3β Activation. 26637370 0 64 theme N-Linked 76:83 arg1 Glycosylation 85:97 N-Linked Glycosylation 76:97 N-Linked Glycosylation 76:97 2-Deoxy-Glucose Downregulates Endothelial AKT and ERK via Interference with N-Linked Glycosylation, Induction of Endoplasmic Reticulum Stress, and GSK3β Activation. 26637370 5 65 from 2-DG 987:990 arg1 mice 1005:1008 LHBETATAG mice 995:1008 LHBETATAG mice 995:1008 In vivo, periocular administration of 2-DG in LHBETATAG mice was associated with significant reduction of newly formed (CD105(+)) tumor capillaries, ER stress (GRP 78 expression), and endothelial apoptosis (TUNEL). 26637370 6 66 theme resistance 1346:1355 arg1 mechanisms 1357:1366 resistance mechanisms 1346:1366 resistance mechanisms 1346:1366 These findings uniquely link N-linked glycosylation inhibition, ER stress, and ERK/AKT downregulation in endothelial cells, and provide a novel drug development strategy to overcome resistance mechanisms to currently available antiangiogenic agents. 26637370 2 67 theme tumor 428:432 arg1 cytotoxicity 434:445 tumor cytotoxicity 428:445 tumor cytotoxicity 428:445 We reported that the glucose analogue 2-deoxy-D-glucose (2-DG) inhibits angiogenesis at significantly lower concentrations than those required for tumor cytotoxicity. 26637370 3 68 theme ERK 654:656 arg1 phosphorylation 658:672 ERK phosphorylation 654:672 ERK phosphorylation 654:672 Here, we found that hypersensitivity to 2-DG in endothelial cells is not associated with enhanced drug uptake compared with tumor cells, but with time-dependent, endothelial-selective inhibition of AKT and ERK phosphorylation. 26637370 3 69 from hypersensitivity 468:483 arg1 cells 508:512 endothelial cells 496:512 endothelial cells 496:512 Here, we found that hypersensitivity to 2-DG in endothelial cells is not associated with enhanced drug uptake compared with tumor cells, but with time-dependent, endothelial-selective inhibition of AKT and ERK phosphorylation. 26637370 1 70 theme angiogenesis 256:267 arg1 inhibition 269:278 angiogenesis inhibition 256:278 angiogenesis inhibition 256:278 Interference with endothelial cell metabolism is a promising, yet unexploited strategy for angiogenesis inhibition. 26991954 11 0 dep Er 1870:1871 arg1 known 1879:1883 known 1879:1883 known as NRS/ER 1879:1893 The ability to identify molecules that inhibit Er (also known as NRS/ER) enzymes or mimic UDP-KDG may lead to the development of new antifungal drugs. 26991954 7 1 theme nucleotide 1172:1181 arg1 sugars 1183:1188 nucleotide sugars 1172:1188 nucleotide sugars 1172:1188 Analysis of nucleotide sugars reveals the accumulation of the UDP-rhamnose pathway intermediate UDP-4-keto-6-deoxy-glucose (UDP-KDG) in hyphae of the Δbcer strain. 26991954 3 2 theme bcer 636:639 arg1 deletion 558:565 deletion 558:565 deletion of bcdh, the first biosynthetic gene in the metabolic pathway, or of bcer, the second gene in the pathway, 558:672 We report here that deletion of bcdh, the first biosynthetic gene in the metabolic pathway, or of bcer, the second gene in the pathway, abolishes the production of rhamnose-containing glycans in these mutant strains. 26991954 2 3 theme corresponding 348:360 arg1 genes 362:366 corresponding genes 348:366 corresponding genes (bcdh, bcer) 348:379 A previous study has identified two enzymes and corresponding genes (bcdh, bcer) that are involved in the biochemical transformation of uridine diphosphate (UDP)-glucose, the major fungal wall nucleotide sugar precursor, to UDP-rhamnose. 26991954 1 4 theme wide 254:257 arg1 range 259:263 a wide range 252:263 a wide range of agriculturally important crops 252:297 Botrytis cinerea is a model plant-pathogenic fungus that causes grey mould and rot diseases in a wide range of agriculturally important crops. 26991954 9 5 theme cell 1622:1625 arg1 composition 1632:1642 cell wall composition 1622:1642 cell wall composition 1622:1642 The correlation between high UDP-KDG and modified cell wall and developmental defects raises the possibility that high levels of UDP-KDG result in deleterious effects on cell wall composition, and hence on virulence. 26991954 10 6 theme first 1681:1685 arg1 This 1669:1672 This 1669:1672 This 1669:1672 This is the first report demonstrating that the accumulation of a minor nucleotide sugar intermediate has such a profound and adverse effect on a fungus. 26991954 10 6 theme first 1681:1685 arg1 report 1687:1692 the first report 1677:1692 the first report demonstrating that the accumulation of a minor nucleotide sugar intermediate has such a profound and adverse effect on a fungus 1677:1820 This is the first report demonstrating that the accumulation of a minor nucleotide sugar intermediate has such a profound and adverse effect on a fungus. 26991954 1 7 theme model 179:183 arg1 fungus 202:207 a model plant-pathogenic fungus 177:207 a model plant-pathogenic fungus that causes grey mould and rot diseases in a wide range of agriculturally important crops 177:297 Botrytis cinerea is a model plant-pathogenic fungus that causes grey mould and rot diseases in a wide range of agriculturally important crops. 26991954 1 7 theme model 179:183 arg1 cinerea 166:172 Botrytis cinerea 157:172 Botrytis cinerea 157:172 Botrytis cinerea is a model plant-pathogenic fungus that causes grey mould and rot diseases in a wide range of agriculturally important crops. 26991954 11 8 theme new 1952:1954 arg1 drugs 1967:1971 new antifungal drugs 1952:1971 new antifungal drugs 1952:1971 The ability to identify molecules that inhibit Er (also known as NRS/ER) enzymes or mimic UDP-KDG may lead to the development of new antifungal drugs. 26991954 9 9 theme deleterious 1599:1609 arg1 effects 1611:1617 deleterious effects 1599:1617 deleterious effects on cell wall composition, and hence on virulence 1599:1666 The correlation between high UDP-KDG and modified cell wall and developmental defects raises the possibility that high levels of UDP-KDG result in deleterious effects on cell wall composition, and hence on virulence. 26991954 11 10 theme antifungal 1956:1965 arg1 drugs 1967:1971 new antifungal drugs 1952:1971 new antifungal drugs 1952:1971 The ability to identify molecules that inhibit Er (also known as NRS/ER) enzymes or mimic UDP-KDG may lead to the development of new antifungal drugs. 26991954 3 11 theme glycans 722:728 arg1 production 688:697 the production 684:697 the production of rhamnose-containing glycans in these mutant strains 684:752 We report here that deletion of bcdh, the first biosynthetic gene in the metabolic pathway, or of bcer, the second gene in the pathway, abolishes the production of rhamnose-containing glycans in these mutant strains. 26991954 3 12 theme bcdh 570:573 arg1 deletion 558:565 deletion 558:565 deletion of bcdh, the first biosynthetic gene in the metabolic pathway, or of bcer, the second gene in the pathway, 558:672 We report here that deletion of bcdh, the first biosynthetic gene in the metabolic pathway, or of bcer, the second gene in the pathway, abolishes the production of rhamnose-containing glycans in these mutant strains. 26991954 4 13 theme apparent 820:827 arg1 effect 829:834 no apparent effect 817:834 no apparent effect 817:834 Deletion of bcdh or double deletion of both bcdh and bcer has no apparent effect on fungal development or pathogenicity. 26991954 8 14 theme fast 1400:1403 arg1 conversion 1405:1414 fast conversion 1400:1414 fast conversion to UDP-rhamnose by the BcEr enzyme 1400:1449 UDP-KDG could not be detected in hyphae of the wild-type strain, indicating fast conversion to UDP-rhamnose by the BcEr enzyme. 26991954 10 15 theme minor 1735:1739 arg1 intermediate 1758:1769 a minor nucleotide sugar intermediate 1733:1769 a minor nucleotide sugar intermediate 1733:1769 This is the first report demonstrating that the accumulation of a minor nucleotide sugar intermediate has such a profound and adverse effect on a fungus. 26991954 6 16 with Treatments 1082:1091 arg1 stressors 1103:1111 wall stressors 1098:1111 wall stressors 1098:1111 Treatments with wall stressors suggest the alteration of cell wall integrity. 26991954 6 17 theme wall 1144:1147 arg1 integrity 1149:1157 cell wall integrity 1139:1157 cell wall integrity 1139:1157 Treatments with wall stressors suggest the alteration of cell wall integrity. 26991954 7 18 theme Δbcer 1310:1314 arg1 strain 1316:1321 the Δbcer strain 1306:1321 the Δbcer strain 1306:1321 Analysis of nucleotide sugars reveals the accumulation of the UDP-rhamnose pathway intermediate UDP-4-keto-6-deoxy-glucose (UDP-KDG) in hyphae of the Δbcer strain. 26991954 5 19 theme hyphal 984:989 arg1 growth 991:996 altered hyphal growth 976:996 altered hyphal growth 976:996 Interestingly, deletion of the bcer gene alone adversely affects fungal development, giving rise to altered hyphal growth and morphology, as well as reduced sporulation, sclerotia production and virulence. 26991954 3 20 theme biosynthetic 586:597 arg1 gene 599:602 the first biosynthetic gene 576:602 the first biosynthetic gene in the metabolic pathway 576:627 We report here that deletion of bcdh, the first biosynthetic gene in the metabolic pathway, or of bcer, the second gene in the pathway, abolishes the production of rhamnose-containing glycans in these mutant strains. 26991954 3 20 theme biosynthetic 586:597 arg1 bcdh 570:573 bcdh 570:573 bcdh 570:573 We report here that deletion of bcdh, the first biosynthetic gene in the metabolic pathway, or of bcer, the second gene in the pathway, abolishes the production of rhamnose-containing glycans in these mutant strains. 26991954 2 21 theme major 475:479 arg1 precursor 510:518 the major fungal wall nucleotide sugar precursor 471:518 the major fungal wall nucleotide sugar precursor 471:518 A previous study has identified two enzymes and corresponding genes (bcdh, bcer) that are involved in the biochemical transformation of uridine diphosphate (UDP)-glucose, the major fungal wall nucleotide sugar precursor, to UDP-rhamnose. 26991954 2 21 theme major 475:479 arg1 uridine 436:442 uridine 436:442 uridine diphosphate (UDP)-glucose 436:468 A previous study has identified two enzymes and corresponding genes (bcdh, bcer) that are involved in the biochemical transformation of uridine diphosphate (UDP)-glucose, the major fungal wall nucleotide sugar precursor, to UDP-rhamnose. 26991954 1 22 theme Botrytis 157:164 arg1 fungus 202:207 a model plant-pathogenic fungus 177:207 a model plant-pathogenic fungus that causes grey mould and rot diseases in a wide range of agriculturally important crops 177:297 Botrytis cinerea is a model plant-pathogenic fungus that causes grey mould and rot diseases in a wide range of agriculturally important crops. 26991954 1 22 theme Botrytis 157:164 arg1 cinerea 166:172 Botrytis cinerea 157:172 Botrytis cinerea 157:172 Botrytis cinerea is a model plant-pathogenic fungus that causes grey mould and rot diseases in a wide range of agriculturally important crops. 26991954 8 23 theme BcEr 1439:1442 arg1 enzyme 1444:1449 the BcEr enzyme 1435:1449 the BcEr enzyme 1435:1449 UDP-KDG could not be detected in hyphae of the wild-type strain, indicating fast conversion to UDP-rhamnose by the BcEr enzyme. 26991954 9 24 theme UDP-KDG 1481:1487 arg1 wall 1507:1510 high UDP-KDG and modified cell wall 1476:1510 high UDP-KDG and modified cell wall 1476:1510 The correlation between high UDP-KDG and modified cell wall and developmental defects raises the possibility that high levels of UDP-KDG result in deleterious effects on cell wall composition, and hence on virulence. 26991954 2 25 theme sugar 504:508 arg1 precursor 510:518 the major fungal wall nucleotide sugar precursor 471:518 the major fungal wall nucleotide sugar precursor 471:518 A previous study has identified two enzymes and corresponding genes (bcdh, bcer) that are involved in the biochemical transformation of uridine diphosphate (UDP)-glucose, the major fungal wall nucleotide sugar precursor, to UDP-rhamnose. 26991954 2 25 theme sugar 504:508 arg1 uridine 436:442 uridine 436:442 uridine diphosphate (UDP)-glucose 436:468 A previous study has identified two enzymes and corresponding genes (bcdh, bcer) that are involved in the biochemical transformation of uridine diphosphate (UDP)-glucose, the major fungal wall nucleotide sugar precursor, to UDP-rhamnose. 26991954 7 26 theme strain 1316:1321 arg1 hyphae 1296:1301 hyphae 1296:1301 hyphae of the Δbcer strain 1296:1321 Analysis of nucleotide sugars reveals the accumulation of the UDP-rhamnose pathway intermediate UDP-4-keto-6-deoxy-glucose (UDP-KDG) in hyphae of the Δbcer strain. 26991954 2 27 dep genes 362:366 arg1 bcer 375:378 bcer 375:378 bcer 375:378 A previous study has identified two enzymes and corresponding genes (bcdh, bcer) that are involved in the biochemical transformation of uridine diphosphate (UDP)-glucose, the major fungal wall nucleotide sugar precursor, to UDP-rhamnose. 26991954 2 27 dep genes 362:366 arg1 bcdh 369:372 bcdh 369:372 bcdh 369:372 A previous study has identified two enzymes and corresponding genes (bcdh, bcer) that are involved in the biochemical transformation of uridine diphosphate (UDP)-glucose, the major fungal wall nucleotide sugar precursor, to UDP-rhamnose. 26991954 9 28 theme modified 1493:1500 arg1 wall 1507:1510 high UDP-KDG and modified cell wall 1476:1510 high UDP-KDG and modified cell wall 1476:1510 The correlation between high UDP-KDG and modified cell wall and developmental defects raises the possibility that high levels of UDP-KDG result in deleterious effects on cell wall composition, and hence on virulence. 26991954 2 29 theme wall 488:491 arg1 precursor 510:518 the major fungal wall nucleotide sugar precursor 471:518 the major fungal wall nucleotide sugar precursor 471:518 A previous study has identified two enzymes and corresponding genes (bcdh, bcer) that are involved in the biochemical transformation of uridine diphosphate (UDP)-glucose, the major fungal wall nucleotide sugar precursor, to UDP-rhamnose. 26991954 2 29 theme wall 488:491 arg1 uridine 436:442 uridine 436:442 uridine diphosphate (UDP)-glucose 436:468 A previous study has identified two enzymes and corresponding genes (bcdh, bcer) that are involved in the biochemical transformation of uridine diphosphate (UDP)-glucose, the major fungal wall nucleotide sugar precursor, to UDP-rhamnose. 26991954 5 30 theme reduced 1025:1031 arg1 sporulation 1033:1043 reduced sporulation 1025:1043 reduced sporulation 1025:1043 Interestingly, deletion of the bcer gene alone adversely affects fungal development, giving rise to altered hyphal growth and morphology, as well as reduced sporulation, sclerotia production and virulence. 26991954 5 31 theme gene 912:915 arg1 deletion 891:898 deletion 891:898 deletion of the bcer gene alone 891:921 Interestingly, deletion of the bcer gene alone adversely affects fungal development, giving rise to altered hyphal growth and morphology, as well as reduced sporulation, sclerotia production and virulence. 26991954 2 32 theme uridine 436:442 arg1 transformation 418:431 the biochemical transformation 402:431 the biochemical transformation of uridine diphosphate (UDP)-glucose, the major fungal wall nucleotide sugar precursor, to UDP-rhamnose 402:535 A previous study has identified two enzymes and corresponding genes (bcdh, bcer) that are involved in the biochemical transformation of uridine diphosphate (UDP)-glucose, the major fungal wall nucleotide sugar precursor, to UDP-rhamnose. 26991954 0 33 theme Genetic 0:6 arg1 alteration 8:17 Genetic alteration 0:17 Genetic alteration of UDP-rhamnose metabolism in Botrytis cinerea 0:64 Genetic alteration of UDP-rhamnose metabolism in Botrytis cinerea leads to the accumulation of UDP-KDG that adversely affects development and pathogenicity. 26991954 9 34 theme developmental 1516:1528 arg1 defects 1530:1536 developmental defects 1516:1536 developmental defects 1516:1536 The correlation between high UDP-KDG and modified cell wall and developmental defects raises the possibility that high levels of UDP-KDG result in deleterious effects on cell wall composition, and hence on virulence. 26991954 11 35 theme Er 1870:1871 arg1 enzymes 1896:1902 Er (also known as NRS/ER) enzymes 1870:1902 Er (also known as NRS/ER) enzymes 1870:1902 The ability to identify molecules that inhibit Er (also known as NRS/ER) enzymes or mimic UDP-KDG may lead to the development of new antifungal drugs. 26991954 1 36 theme crops 293:297 arg1 range 259:263 a wide range 252:263 a wide range of agriculturally important crops 252:297 Botrytis cinerea is a model plant-pathogenic fungus that causes grey mould and rot diseases in a wide range of agriculturally important crops. 26991954 10 37 contain has 1771:1773 arg1 accumulation 1717:1728 the accumulation 1713:1728 the accumulation of a minor nucleotide sugar intermediate 1713:1769 This is the first report demonstrating that the accumulation of a minor nucleotide sugar intermediate has such a profound and adverse effect on a fungus. 26991954 10 37 contain has 1771:1773 arg2 effect 1803:1808 such a profound and adverse effect 1775:1808 such a profound and adverse effect 1775:1808 This is the first report demonstrating that the accumulation of a minor nucleotide sugar intermediate has such a profound and adverse effect on a fungus. 26991954 3 38 theme metabolic 611:619 arg1 pathway 621:627 the metabolic pathway 607:627 the metabolic pathway 607:627 We report here that deletion of bcdh, the first biosynthetic gene in the metabolic pathway, or of bcer, the second gene in the pathway, abolishes the production of rhamnose-containing glycans in these mutant strains. 26991954 0 39 theme metabolism 35:44 arg1 alteration 8:17 Genetic alteration 0:17 Genetic alteration of UDP-rhamnose metabolism in Botrytis cinerea 0:64 Genetic alteration of UDP-rhamnose metabolism in Botrytis cinerea leads to the accumulation of UDP-KDG that adversely affects development and pathogenicity. 26991954 7 40 theme intermediate 1243:1254 arg1 UDP-4-keto-6-deoxy-glucose 1256:1281 the UDP-rhamnose pathway intermediate UDP-4-keto-6-deoxy-glucose 1218:1281 the UDP-rhamnose pathway intermediate UDP-4-keto-6-deoxy-glucose (UDP-KDG) 1218:1291 Analysis of nucleotide sugars reveals the accumulation of the UDP-rhamnose pathway intermediate UDP-4-keto-6-deoxy-glucose (UDP-KDG) in hyphae of the Δbcer strain. 26991954 7 40 theme intermediate 1243:1254 arg1 UDP-KDG 1284:1290 UDP-KDG 1284:1290 UDP-KDG 1284:1290 Analysis of nucleotide sugars reveals the accumulation of the UDP-rhamnose pathway intermediate UDP-4-keto-6-deoxy-glucose (UDP-KDG) in hyphae of the Δbcer strain. 26991954 0 41 theme Botrytis 49:56 arg1 cinerea 58:64 Botrytis cinerea 49:64 Botrytis cinerea 49:64 Genetic alteration of UDP-rhamnose metabolism in Botrytis cinerea leads to the accumulation of UDP-KDG that adversely affects development and pathogenicity. 26991954 10 42 theme profound 1782:1789 arg1 effect 1803:1808 such a profound and adverse effect 1775:1808 such a profound and adverse effect 1775:1808 This is the first report demonstrating that the accumulation of a minor nucleotide sugar intermediate has such a profound and adverse effect on a fungus. 26991954 9 43 theme wall 1627:1630 arg1 composition 1632:1642 cell wall composition 1622:1642 cell wall composition 1622:1642 The correlation between high UDP-KDG and modified cell wall and developmental defects raises the possibility that high levels of UDP-KDG result in deleterious effects on cell wall composition, and hence on virulence. 26991954 7 44 theme UDP-rhamnose 1222:1233 arg1 UDP-4-keto-6-deoxy-glucose 1256:1281 the UDP-rhamnose pathway intermediate UDP-4-keto-6-deoxy-glucose 1218:1281 the UDP-rhamnose pathway intermediate UDP-4-keto-6-deoxy-glucose (UDP-KDG) 1218:1291 Analysis of nucleotide sugars reveals the accumulation of the UDP-rhamnose pathway intermediate UDP-4-keto-6-deoxy-glucose (UDP-KDG) in hyphae of the Δbcer strain. 26991954 7 44 theme UDP-rhamnose 1222:1233 arg1 UDP-KDG 1284:1290 UDP-KDG 1284:1290 UDP-KDG 1284:1290 Analysis of nucleotide sugars reveals the accumulation of the UDP-rhamnose pathway intermediate UDP-4-keto-6-deoxy-glucose (UDP-KDG) in hyphae of the Δbcer strain. 26991954 8 45 theme strain 1381:1386 arg1 hyphae 1357:1362 hyphae 1357:1362 hyphae of the wild-type strain 1357:1386 UDP-KDG could not be detected in hyphae of the wild-type strain, indicating fast conversion to UDP-rhamnose by the BcEr enzyme. 26991954 11 46 dep known 1879:1883 arg1 also 1874:1877 also 1874:1877 also 1874:1877 The ability to identify molecules that inhibit Er (also known as NRS/ER) enzymes or mimic UDP-KDG may lead to the development of new antifungal drugs. 26991954 5 47 theme fungal 941:946 arg1 development 948:958 fungal development 941:958 fungal development 941:958 Interestingly, deletion of the bcer gene alone adversely affects fungal development, giving rise to altered hyphal growth and morphology, as well as reduced sporulation, sclerotia production and virulence. 26991954 3 48 theme second 646:651 arg1 bcer 636:639 bcer 636:639 bcer 636:639 We report here that deletion of bcdh, the first biosynthetic gene in the metabolic pathway, or of bcer, the second gene in the pathway, abolishes the production of rhamnose-containing glycans in these mutant strains. 26991954 3 48 theme second 646:651 arg1 gene 653:656 the second gene 642:656 the second gene in the pathway 642:671 We report here that deletion of bcdh, the first biosynthetic gene in the metabolic pathway, or of bcer, the second gene in the pathway, abolishes the production of rhamnose-containing glycans in these mutant strains. 26991954 4 49 theme bcdh 799:802 arg1 deletion 782:789 double deletion 775:789 double deletion of both bcdh and bcer 775:811 Deletion of bcdh or double deletion of both bcdh and bcer has no apparent effect on fungal development or pathogenicity. 26991954 4 49 theme bcdh 799:802 arg1 Deletion 755:762 Deletion 755:762 Deletion of bcdh 755:770 Deletion of bcdh or double deletion of both bcdh and bcer has no apparent effect on fungal development or pathogenicity. 26991954 7 50 theme sugars 1183:1188 arg1 Analysis 1160:1167 Analysis 1160:1167 Analysis of nucleotide sugars 1160:1188 Analysis of nucleotide sugars reveals the accumulation of the UDP-rhamnose pathway intermediate UDP-4-keto-6-deoxy-glucose (UDP-KDG) in hyphae of the Δbcer strain. 26991954 3 51 from gene 599:602 arg1 pathway 621:627 the metabolic pathway 607:627 the metabolic pathway 607:627 We report here that deletion of bcdh, the first biosynthetic gene in the metabolic pathway, or of bcer, the second gene in the pathway, abolishes the production of rhamnose-containing glycans in these mutant strains. 26991954 4 52 theme bcer 808:811 arg1 deletion 782:789 double deletion 775:789 double deletion of both bcdh and bcer 775:811 Deletion of bcdh or double deletion of both bcdh and bcer has no apparent effect on fungal development or pathogenicity. 26991954 4 52 theme bcer 808:811 arg1 Deletion 755:762 Deletion 755:762 Deletion of bcdh 755:770 Deletion of bcdh or double deletion of both bcdh and bcer has no apparent effect on fungal development or pathogenicity. 26991954 4 53 theme double 775:780 arg1 deletion 782:789 double deletion 775:789 double deletion of both bcdh and bcer 775:811 Deletion of bcdh or double deletion of both bcdh and bcer has no apparent effect on fungal development or pathogenicity. 26991954 7 54 from accumulation 1202:1213 arg1 hyphae 1296:1301 hyphae 1296:1301 hyphae of the Δbcer strain 1296:1321 Analysis of nucleotide sugars reveals the accumulation of the UDP-rhamnose pathway intermediate UDP-4-keto-6-deoxy-glucose (UDP-KDG) in hyphae of the Δbcer strain. 26991954 6 55 theme wall 1098:1101 arg1 stressors 1103:1111 wall stressors 1098:1111 wall stressors 1098:1111 Treatments with wall stressors suggest the alteration of cell wall integrity. 26991954 3 56 from gene 653:656 arg1 pathway 665:671 the pathway 661:671 the pathway 661:671 We report here that deletion of bcdh, the first biosynthetic gene in the metabolic pathway, or of bcer, the second gene in the pathway, abolishes the production of rhamnose-containing glycans in these mutant strains. 26991954 1 57 theme plant-pathogenic 185:200 arg1 fungus 202:207 a model plant-pathogenic fungus 177:207 a model plant-pathogenic fungus that causes grey mould and rot diseases in a wide range of agriculturally important crops 177:297 Botrytis cinerea is a model plant-pathogenic fungus that causes grey mould and rot diseases in a wide range of agriculturally important crops. 26991954 1 57 theme plant-pathogenic 185:200 arg1 cinerea 166:172 Botrytis cinerea 157:172 Botrytis cinerea 157:172 Botrytis cinerea is a model plant-pathogenic fungus that causes grey mould and rot diseases in a wide range of agriculturally important crops. 26991954 8 58 located detected 1345:1352 arg2 UDP-KDG 1324:1330 UDP-KDG 1324:1330 UDP-KDG 1324:1330 UDP-KDG could not be detected in hyphae of the wild-type strain, indicating fast conversion to UDP-rhamnose by the BcEr enzyme. 26991954 8 58 located detected 1345:1352 arg1 hyphae 1357:1362 hyphae 1357:1362 hyphae of the wild-type strain 1357:1386 UDP-KDG could not be detected in hyphae of the wild-type strain, indicating fast conversion to UDP-rhamnose by the BcEr enzyme. 26991954 9 59 theme high 1566:1569 arg1 levels 1571:1576 high levels 1566:1576 high levels of UDP-KDG 1566:1587 The correlation between high UDP-KDG and modified cell wall and developmental defects raises the possibility that high levels of UDP-KDG result in deleterious effects on cell wall composition, and hence on virulence. 26991954 2 60 theme previous 302:309 arg1 study 311:315 A previous study 300:315 A previous study 300:315 A previous study has identified two enzymes and corresponding genes (bcdh, bcer) that are involved in the biochemical transformation of uridine diphosphate (UDP)-glucose, the major fungal wall nucleotide sugar precursor, to UDP-rhamnose. 26991954 4 61 theme fungal 839:844 arg1 development 846:856 development 846:856 development 846:856 Deletion of bcdh or double deletion of both bcdh and bcer has no apparent effect on fungal development or pathogenicity. 26991954 10 62 theme intermediate 1758:1769 arg1 accumulation 1717:1728 the accumulation 1713:1728 the accumulation of a minor nucleotide sugar intermediate 1713:1769 This is the first report demonstrating that the accumulation of a minor nucleotide sugar intermediate has such a profound and adverse effect on a fungus. 26991954 1 63 theme grey 221:224 arg1 mould 226:230 grey mould 221:230 grey mould 221:230 Botrytis cinerea is a model plant-pathogenic fungus that causes grey mould and rot diseases in a wide range of agriculturally important crops. 26991954 9 64 from effects 1611:1617 arg1 virulence 1658:1666 virulence 1658:1666 virulence 1658:1666 The correlation between high UDP-KDG and modified cell wall and developmental defects raises the possibility that high levels of UDP-KDG result in deleterious effects on cell wall composition, and hence on virulence. 26991954 9 64 from effects 1611:1617 arg1 composition 1632:1642 cell wall composition 1622:1642 cell wall composition 1622:1642 The correlation between high UDP-KDG and modified cell wall and developmental defects raises the possibility that high levels of UDP-KDG result in deleterious effects on cell wall composition, and hence on virulence. 26991954 11 65 theme drugs 1967:1971 arg1 development 1937:1947 the development 1933:1947 the development of new antifungal drugs 1933:1971 The ability to identify molecules that inhibit Er (also known as NRS/ER) enzymes or mimic UDP-KDG may lead to the development of new antifungal drugs. 26991954 10 66 theme nucleotide 1741:1750 arg1 intermediate 1758:1769 a minor nucleotide sugar intermediate 1733:1769 a minor nucleotide sugar intermediate 1733:1769 This is the first report demonstrating that the accumulation of a minor nucleotide sugar intermediate has such a profound and adverse effect on a fungus. 26991954 6 67 theme integrity 1149:1157 arg1 alteration 1125:1134 the alteration 1121:1134 the alteration of cell wall integrity 1121:1157 Treatments with wall stressors suggest the alteration of cell wall integrity. 26991954 3 68 theme rhamnose-containing 702:720 arg1 glycans 722:728 rhamnose-containing glycans 702:728 rhamnose-containing glycans 702:728 We report here that deletion of bcdh, the first biosynthetic gene in the metabolic pathway, or of bcer, the second gene in the pathway, abolishes the production of rhamnose-containing glycans in these mutant strains. 26991954 5 69 theme altered 976:982 arg1 growth 991:996 altered hyphal growth 976:996 altered hyphal growth 976:996 Interestingly, deletion of the bcer gene alone adversely affects fungal development, giving rise to altered hyphal growth and morphology, as well as reduced sporulation, sclerotia production and virulence. 26991954 3 70 theme first 580:584 arg1 gene 599:602 the first biosynthetic gene 576:602 the first biosynthetic gene in the metabolic pathway 576:627 We report here that deletion of bcdh, the first biosynthetic gene in the metabolic pathway, or of bcer, the second gene in the pathway, abolishes the production of rhamnose-containing glycans in these mutant strains. 26991954 3 70 theme first 580:584 arg1 bcdh 570:573 bcdh 570:573 bcdh 570:573 We report here that deletion of bcdh, the first biosynthetic gene in the metabolic pathway, or of bcer, the second gene in the pathway, abolishes the production of rhamnose-containing glycans in these mutant strains. 26991954 6 71 theme cell 1139:1142 arg1 integrity 1149:1157 cell wall integrity 1139:1157 cell wall integrity 1139:1157 Treatments with wall stressors suggest the alteration of cell wall integrity. 26991954 3 72 theme mutant 739:744 arg1 strains 746:752 these mutant strains 733:752 these mutant strains 733:752 We report here that deletion of bcdh, the first biosynthetic gene in the metabolic pathway, or of bcer, the second gene in the pathway, abolishes the production of rhamnose-containing glycans in these mutant strains. 26991954 5 73 theme sclerotia 1046:1054 arg1 production 1056:1065 sclerotia production 1046:1065 sclerotia production 1046:1065 Interestingly, deletion of the bcer gene alone adversely affects fungal development, giving rise to altered hyphal growth and morphology, as well as reduced sporulation, sclerotia production and virulence. 26991954 9 74 theme high 1476:1479 arg1 wall 1507:1510 high UDP-KDG and modified cell wall 1476:1510 high UDP-KDG and modified cell wall 1476:1510 The correlation between high UDP-KDG and modified cell wall and developmental defects raises the possibility that high levels of UDP-KDG result in deleterious effects on cell wall composition, and hence on virulence. 26991954 4 75 contain has 813:815 arg1 deletion 782:789 double deletion 775:789 double deletion of both bcdh and bcer 775:811 Deletion of bcdh or double deletion of both bcdh and bcer has no apparent effect on fungal development or pathogenicity. 26991954 4 75 contain has 813:815 arg1 Deletion 755:762 Deletion 755:762 Deletion of bcdh 755:770 Deletion of bcdh or double deletion of both bcdh and bcer has no apparent effect on fungal development or pathogenicity. 26991954 4 75 contain has 813:815 arg2 effect 829:834 no apparent effect 817:834 no apparent effect 817:834 Deletion of bcdh or double deletion of both bcdh and bcer has no apparent effect on fungal development or pathogenicity. 26991954 2 76 theme -glucose 461:468 arg1 precursor 510:518 the major fungal wall nucleotide sugar precursor 471:518 the major fungal wall nucleotide sugar precursor 471:518 A previous study has identified two enzymes and corresponding genes (bcdh, bcer) that are involved in the biochemical transformation of uridine diphosphate (UDP)-glucose, the major fungal wall nucleotide sugar precursor, to UDP-rhamnose. 26991954 2 76 theme -glucose 461:468 arg1 uridine 436:442 uridine 436:442 uridine diphosphate (UDP)-glucose 436:468 A previous study has identified two enzymes and corresponding genes (bcdh, bcer) that are involved in the biochemical transformation of uridine diphosphate (UDP)-glucose, the major fungal wall nucleotide sugar precursor, to UDP-rhamnose. 26991954 0 77 from alteration 8:17 arg1 cinerea 58:64 Botrytis cinerea 49:64 Botrytis cinerea 49:64 Genetic alteration of UDP-rhamnose metabolism in Botrytis cinerea leads to the accumulation of UDP-KDG that adversely affects development and pathogenicity. 26991954 0 78 theme UDP-KDG 95:101 arg1 accumulation 79:90 the accumulation 75:90 the accumulation of UDP-KDG that adversely affects development and pathogenicity 75:154 Genetic alteration of UDP-rhamnose metabolism in Botrytis cinerea leads to the accumulation of UDP-KDG that adversely affects development and pathogenicity. 26991954 2 79 theme nucleotide 493:502 arg1 precursor 510:518 the major fungal wall nucleotide sugar precursor 471:518 the major fungal wall nucleotide sugar precursor 471:518 A previous study has identified two enzymes and corresponding genes (bcdh, bcer) that are involved in the biochemical transformation of uridine diphosphate (UDP)-glucose, the major fungal wall nucleotide sugar precursor, to UDP-rhamnose. 26991954 2 79 theme nucleotide 493:502 arg1 uridine 436:442 uridine 436:442 uridine diphosphate (UDP)-glucose 436:468 A previous study has identified two enzymes and corresponding genes (bcdh, bcer) that are involved in the biochemical transformation of uridine diphosphate (UDP)-glucose, the major fungal wall nucleotide sugar precursor, to UDP-rhamnose. 26991954 5 80 theme bcer 907:910 arg1 gene 912:915 the bcer gene 903:915 the bcer gene 903:915 Interestingly, deletion of the bcer gene alone adversely affects fungal development, giving rise to altered hyphal growth and morphology, as well as reduced sporulation, sclerotia production and virulence. 26991954 2 81 theme fungal 481:486 arg1 precursor 510:518 the major fungal wall nucleotide sugar precursor 471:518 the major fungal wall nucleotide sugar precursor 471:518 A previous study has identified two enzymes and corresponding genes (bcdh, bcer) that are involved in the biochemical transformation of uridine diphosphate (UDP)-glucose, the major fungal wall nucleotide sugar precursor, to UDP-rhamnose. 26991954 2 81 theme fungal 481:486 arg1 uridine 436:442 uridine 436:442 uridine diphosphate (UDP)-glucose 436:468 A previous study has identified two enzymes and corresponding genes (bcdh, bcer) that are involved in the biochemical transformation of uridine diphosphate (UDP)-glucose, the major fungal wall nucleotide sugar precursor, to UDP-rhamnose. 26991954 3 82 from production 688:697 arg1 strains 746:752 these mutant strains 733:752 these mutant strains 733:752 We report here that deletion of bcdh, the first biosynthetic gene in the metabolic pathway, or of bcer, the second gene in the pathway, abolishes the production of rhamnose-containing glycans in these mutant strains. 26991954 0 83 theme UDP-rhamnose 22:33 arg1 metabolism 35:44 UDP-rhamnose metabolism 22:44 UDP-rhamnose metabolism 22:44 Genetic alteration of UDP-rhamnose metabolism in Botrytis cinerea leads to the accumulation of UDP-KDG that adversely affects development and pathogenicity. 26991954 1 84 theme important 283:291 arg1 crops 293:297 agriculturally important crops 268:297 agriculturally important crops 268:297 Botrytis cinerea is a model plant-pathogenic fungus that causes grey mould and rot diseases in a wide range of agriculturally important crops. 26991954 7 85 theme UDP-4-keto-6-deoxy-glucose 1256:1281 arg1 accumulation 1202:1213 the accumulation 1198:1213 the accumulation of the UDP-rhamnose pathway intermediate UDP-4-keto-6-deoxy-glucose (UDP-KDG) in hyphae of the Δbcer strain 1198:1321 Analysis of nucleotide sugars reveals the accumulation of the UDP-rhamnose pathway intermediate UDP-4-keto-6-deoxy-glucose (UDP-KDG) in hyphae of the Δbcer strain. 26991954 2 86 theme biochemical 406:416 arg1 transformation 418:431 the biochemical transformation 402:431 the biochemical transformation of uridine diphosphate (UDP)-glucose, the major fungal wall nucleotide sugar precursor, to UDP-rhamnose 402:535 A previous study has identified two enzymes and corresponding genes (bcdh, bcer) that are involved in the biochemical transformation of uridine diphosphate (UDP)-glucose, the major fungal wall nucleotide sugar precursor, to UDP-rhamnose. 26991954 9 87 theme cell 1502:1505 arg1 wall 1507:1510 high UDP-KDG and modified cell wall 1476:1510 high UDP-KDG and modified cell wall 1476:1510 The correlation between high UDP-KDG and modified cell wall and developmental defects raises the possibility that high levels of UDP-KDG result in deleterious effects on cell wall composition, and hence on virulence. 26991954 7 88 theme pathway 1235:1241 arg1 UDP-4-keto-6-deoxy-glucose 1256:1281 the UDP-rhamnose pathway intermediate UDP-4-keto-6-deoxy-glucose 1218:1281 the UDP-rhamnose pathway intermediate UDP-4-keto-6-deoxy-glucose (UDP-KDG) 1218:1291 Analysis of nucleotide sugars reveals the accumulation of the UDP-rhamnose pathway intermediate UDP-4-keto-6-deoxy-glucose (UDP-KDG) in hyphae of the Δbcer strain. 26991954 7 88 theme pathway 1235:1241 arg1 UDP-KDG 1284:1290 UDP-KDG 1284:1290 UDP-KDG 1284:1290 Analysis of nucleotide sugars reveals the accumulation of the UDP-rhamnose pathway intermediate UDP-4-keto-6-deoxy-glucose (UDP-KDG) in hyphae of the Δbcer strain. 26991954 10 89 theme adverse 1795:1801 arg1 effect 1803:1808 such a profound and adverse effect 1775:1808 such a profound and adverse effect 1775:1808 This is the first report demonstrating that the accumulation of a minor nucleotide sugar intermediate has such a profound and adverse effect on a fungus. 26991954 4 90 theme bcdh 767:770 arg1 deletion 782:789 double deletion 775:789 double deletion of both bcdh and bcer 775:811 Deletion of bcdh or double deletion of both bcdh and bcer has no apparent effect on fungal development or pathogenicity. 26991954 4 90 theme bcdh 767:770 arg1 Deletion 755:762 Deletion 755:762 Deletion of bcdh 755:770 Deletion of bcdh or double deletion of both bcdh and bcer has no apparent effect on fungal development or pathogenicity. 26991954 10 91 theme sugar 1752:1756 arg1 intermediate 1758:1769 a minor nucleotide sugar intermediate 1733:1769 a minor nucleotide sugar intermediate 1733:1769 This is the first report demonstrating that the accumulation of a minor nucleotide sugar intermediate has such a profound and adverse effect on a fungus. 26991954 1 92 theme rot 236:238 arg1 diseases 240:247 rot diseases 236:247 rot diseases 236:247 Botrytis cinerea is a model plant-pathogenic fungus that causes grey mould and rot diseases in a wide range of agriculturally important crops. 26991954 9 93 theme UDP-KDG 1581:1587 arg1 levels 1571:1576 high levels 1566:1576 high levels of UDP-KDG 1566:1587 The correlation between high UDP-KDG and modified cell wall and developmental defects raises the possibility that high levels of UDP-KDG result in deleterious effects on cell wall composition, and hence on virulence. 26991954 8 94 theme wild-type 1371:1379 arg1 strain 1381:1386 the wild-type strain 1367:1386 the wild-type strain 1367:1386 UDP-KDG could not be detected in hyphae of the wild-type strain, indicating fast conversion to UDP-rhamnose by the BcEr enzyme. 25304981 7 0 theme reduced 1497:1503 arg1 levels 1505:1510 reduced levels 1497:1510 reduced levels of complex N-linked glycans 1497:1538 Decreased binding of Phaseolus vulgaris lectin and phytohaemagglutinin to IGF1R immunoprecipitated from treated explants demonstrated reduced levels of complex N-linked glycans. 25304981 2 1 theme age 611:613 arg1 women 589:593 women 589:593 women of reproductive age 589:613 Affected individuals are often treated with statins (3-hydroxy-3-methylglutaryl co-enzyme A [HMG CoA] reductase inhibitors) to reduce circulating cholesterol levels and the risk of developing cardiovascular disease; given the evolving demographic profile of these conditions, such drugs are increasingly prescribed to women of reproductive age. 25304981 6 2 theme trimester 1073:1081 arg1 explants 1098:1105 first trimester villous tissue explants 1067:1105 first trimester villous tissue explants 1067:1105 Treatment of first trimester villous tissue explants with statins (pravastatin or cerivastatin) or inhibitors of N-glycosylation (tunicamycin, deoxymannojirimycin or castanospermine) altered receptor distribution in trophoblast and attenuated proliferation induced by IGF-I or IGF-II (Ki67; P < 0.05, n = 5). 25304981 9 3 theme IGF1R 1948:1952 arg1 expression 1927:1936 subsequent expression 1916:1936 subsequent expression 1916:1936 These data suggest that statins attenuate IGF actions in the placenta by inhibiting N-linked glycosylation and subsequent expression of mature IGF1R at the placental cell surface. 25304981 9 3 theme IGF1R 1948:1952 arg1 glycosylation 1898:1910 N-linked glycosylation 1889:1910 N-linked glycosylation 1889:1910 These data suggest that statins attenuate IGF actions in the placenta by inhibiting N-linked glycosylation and subsequent expression of mature IGF1R at the placental cell surface. 25304981 8 4 theme dolichol 1645:1652 arg1 intermediates 1654:1666 dolichol intermediates 1645:1666 dolichol intermediates 1645:1666 Co-incubation of tissue explants with statins and farnesyl pyrophosphate (which increases the supply of dolichol intermediates), prevented statin-mediated disruption of IGF1R localization and reversed the negative effect on IGF-mediated trophoblast proliferation. 25304981 2 5 theme co-enzyme 351:359 arg1 inhibitors 383:392 3-hydroxy-3-methylglutaryl co-enzyme A [HMG CoA] reductase inhibitors 324:392 3-hydroxy-3-methylglutaryl co-enzyme A [HMG CoA] reductase inhibitors 324:392 Affected individuals are often treated with statins (3-hydroxy-3-methylglutaryl co-enzyme A [HMG CoA] reductase inhibitors) to reduce circulating cholesterol levels and the risk of developing cardiovascular disease; given the evolving demographic profile of these conditions, such drugs are increasingly prescribed to women of reproductive age. 25304981 2 5 theme co-enzyme 351:359 arg1 statins 315:321 statins 315:321 statins (3-hydroxy-3-methylglutaryl co-enzyme A [HMG CoA] reductase inhibitors) 315:393 Affected individuals are often treated with statins (3-hydroxy-3-methylglutaryl co-enzyme A [HMG CoA] reductase inhibitors) to reduce circulating cholesterol levels and the risk of developing cardiovascular disease; given the evolving demographic profile of these conditions, such drugs are increasingly prescribed to women of reproductive age. 25304981 1 6 theme problems 240:247 arg1 problems 240:247 the major healthcare problems 219:247 the major healthcare problems of the Western world 219:268 The rapid rise in obesity, metabolic syndrome and type 2 diabetes is one of the major healthcare problems of the Western world. 25304981 1 6 theme problems 240:247 arg1 one 212:214 one 212:214 one 212:214 The rapid rise in obesity, metabolic syndrome and type 2 diabetes is one of the major healthcare problems of the Western world. 25304981 1 6 theme problems 240:247 arg1 rise 153:156 The rapid rise 143:156 The rapid rise in obesity, metabolic syndrome and type 2 diabetes 143:207 The rapid rise in obesity, metabolic syndrome and type 2 diabetes is one of the major healthcare problems of the Western world. 25304981 6 7 theme N-glycosylation 1167:1181 arg1 deoxymannojirimycin 1197:1215 deoxymannojirimycin 1197:1215 deoxymannojirimycin 1197:1215 Treatment of first trimester villous tissue explants with statins (pravastatin or cerivastatin) or inhibitors of N-glycosylation (tunicamycin, deoxymannojirimycin or castanospermine) altered receptor distribution in trophoblast and attenuated proliferation induced by IGF-I or IGF-II (Ki67; P < 0.05, n = 5). 25304981 6 7 theme N-glycosylation 1167:1181 arg1 statins 1112:1118 statins 1112:1118 statins (pravastatin or cerivastatin) 1112:1148 Treatment of first trimester villous tissue explants with statins (pravastatin or cerivastatin) or inhibitors of N-glycosylation (tunicamycin, deoxymannojirimycin or castanospermine) altered receptor distribution in trophoblast and attenuated proliferation induced by IGF-I or IGF-II (Ki67; P < 0.05, n = 5). 25304981 6 7 theme N-glycosylation 1167:1181 arg1 inhibitors 1153:1162 inhibitors 1153:1162 inhibitors of N-glycosylation (tunicamycin, deoxymannojirimycin or castanospermine) 1153:1235 Treatment of first trimester villous tissue explants with statins (pravastatin or cerivastatin) or inhibitors of N-glycosylation (tunicamycin, deoxymannojirimycin or castanospermine) altered receptor distribution in trophoblast and attenuated proliferation induced by IGF-I or IGF-II (Ki67; P < 0.05, n = 5). 25304981 6 7 theme N-glycosylation 1167:1181 arg1 castanospermine 1220:1234 castanospermine 1220:1234 castanospermine 1220:1234 Treatment of first trimester villous tissue explants with statins (pravastatin or cerivastatin) or inhibitors of N-glycosylation (tunicamycin, deoxymannojirimycin or castanospermine) altered receptor distribution in trophoblast and attenuated proliferation induced by IGF-I or IGF-II (Ki67; P < 0.05, n = 5). 25304981 6 7 theme N-glycosylation 1167:1181 arg1 pravastatin 1121:1131 pravastatin 1121:1131 pravastatin 1121:1131 Treatment of first trimester villous tissue explants with statins (pravastatin or cerivastatin) or inhibitors of N-glycosylation (tunicamycin, deoxymannojirimycin or castanospermine) altered receptor distribution in trophoblast and attenuated proliferation induced by IGF-I or IGF-II (Ki67; P < 0.05, n = 5). 25304981 6 7 theme N-glycosylation 1167:1181 arg1 cerivastatin 1136:1147 cerivastatin 1136:1147 cerivastatin 1136:1147 Treatment of first trimester villous tissue explants with statins (pravastatin or cerivastatin) or inhibitors of N-glycosylation (tunicamycin, deoxymannojirimycin or castanospermine) altered receptor distribution in trophoblast and attenuated proliferation induced by IGF-I or IGF-II (Ki67; P < 0.05, n = 5). 25304981 6 7 theme N-glycosylation 1167:1181 arg1 tunicamycin 1184:1194 tunicamycin 1184:1194 tunicamycin 1184:1194 Treatment of first trimester villous tissue explants with statins (pravastatin or cerivastatin) or inhibitors of N-glycosylation (tunicamycin, deoxymannojirimycin or castanospermine) altered receptor distribution in trophoblast and attenuated proliferation induced by IGF-I or IGF-II (Ki67; P < 0.05, n = 5). 25304981 3 8 theme factors 729:735 arg1 action 699:704 the action 695:704 the action of insulin-like growth factors (IGF)-I and -II which are key regulators of trophoblast proliferation and placental development 695:831 We have previously shown that exposure of placental tissue to statins inhibits the action of insulin-like growth factors (IGF)-I and -II which are key regulators of trophoblast proliferation and placental development. 25304981 7 9 theme vulgaris 1394:1401 arg1 binding 1373:1379 Decreased binding 1363:1379 Decreased binding of Phaseolus vulgaris lectin and phytohaemagglutinin to IGF1R immunoprecipitated from treated explants 1363:1482 Decreased binding of Phaseolus vulgaris lectin and phytohaemagglutinin to IGF1R immunoprecipitated from treated explants demonstrated reduced levels of complex N-linked glycans. 25304981 9 10 theme cell 1971:1974 arg1 surface 1976:1982 the placental cell surface 1957:1982 the placental cell surface 1957:1982 These data suggest that statins attenuate IGF actions in the placenta by inhibiting N-linked glycosylation and subsequent expression of mature IGF1R at the placental cell surface. 25304981 3 11 theme insulin-like 709:720 arg1 -I 742:743 -I 742:743 -I 742:743 We have previously shown that exposure of placental tissue to statins inhibits the action of insulin-like growth factors (IGF)-I and -II which are key regulators of trophoblast proliferation and placental development. 25304981 3 11 theme insulin-like 709:720 arg1 IGF 738:740 IGF 738:740 IGF 738:740 We have previously shown that exposure of placental tissue to statins inhibits the action of insulin-like growth factors (IGF)-I and -II which are key regulators of trophoblast proliferation and placental development. 25304981 3 11 theme insulin-like 709:720 arg1 factors 729:735 insulin-like growth factors 709:735 insulin-like growth factors (IGF)-I and -II which are key regulators of trophoblast proliferation and placental development 709:831 We have previously shown that exposure of placental tissue to statins inhibits the action of insulin-like growth factors (IGF)-I and -II which are key regulators of trophoblast proliferation and placental development. 25304981 3 11 theme insulin-like 709:720 arg1 regulators 767:776 key regulators 763:776 key regulators of trophoblast proliferation and placental development 763:831 We have previously shown that exposure of placental tissue to statins inhibits the action of insulin-like growth factors (IGF)-I and -II which are key regulators of trophoblast proliferation and placental development. 25304981 3 11 theme insulin-like 709:720 arg1 -II 749:751 -II 749:751 -II 749:751 We have previously shown that exposure of placental tissue to statins inhibits the action of insulin-like growth factors (IGF)-I and -II which are key regulators of trophoblast proliferation and placental development. 25304981 6 12 from distribution 1254:1265 arg1 trophoblast 1270:1280 trophoblast 1270:1280 trophoblast 1270:1280 Treatment of first trimester villous tissue explants with statins (pravastatin or cerivastatin) or inhibitors of N-glycosylation (tunicamycin, deoxymannojirimycin or castanospermine) altered receptor distribution in trophoblast and attenuated proliferation induced by IGF-I or IGF-II (Ki67; P < 0.05, n = 5). 25304981 1 13 theme metabolic 170:178 arg1 syndrome 180:187 metabolic syndrome 170:187 metabolic syndrome 170:187 The rapid rise in obesity, metabolic syndrome and type 2 diabetes is one of the major healthcare problems of the Western world. 25304981 6 14 theme receptor 1245:1252 arg1 distribution 1254:1265 receptor distribution 1245:1265 receptor distribution in trophoblast 1245:1280 Treatment of first trimester villous tissue explants with statins (pravastatin or cerivastatin) or inhibitors of N-glycosylation (tunicamycin, deoxymannojirimycin or castanospermine) altered receptor distribution in trophoblast and attenuated proliferation induced by IGF-I or IGF-II (Ki67; P < 0.05, n = 5). 25304981 8 15 theme IGF-mediated 1765:1776 arg1 proliferation 1790:1802 IGF-mediated trophoblast proliferation 1765:1802 IGF-mediated trophoblast proliferation 1765:1802 Co-incubation of tissue explants with statins and farnesyl pyrophosphate (which increases the supply of dolichol intermediates), prevented statin-mediated disruption of IGF1R localization and reversed the negative effect on IGF-mediated trophoblast proliferation. 25304981 4 16 theme IGF 858:860 arg1 receptor 862:869 the IGF receptor 854:869 the IGF receptor 854:869 N-linked glycans in the IGF receptor, IGF1R, influence its presentation at the cell surface. 25304981 4 16 theme IGF 858:860 arg1 IGF1R 872:876 IGF1R 872:876 IGF1R 872:876 N-linked glycans in the IGF receptor, IGF1R, influence its presentation at the cell surface. 25304981 7 17 theme Decreased 1363:1371 arg1 binding 1373:1379 Decreased binding 1363:1379 Decreased binding of Phaseolus vulgaris lectin and phytohaemagglutinin to IGF1R immunoprecipitated from treated explants 1363:1482 Decreased binding of Phaseolus vulgaris lectin and phytohaemagglutinin to IGF1R immunoprecipitated from treated explants demonstrated reduced levels of complex N-linked glycans. 25304981 6 18 dep inhibitors 1153:1162 arg1 castanospermine 1220:1234 castanospermine 1220:1234 castanospermine 1220:1234 Treatment of first trimester villous tissue explants with statins (pravastatin or cerivastatin) or inhibitors of N-glycosylation (tunicamycin, deoxymannojirimycin or castanospermine) altered receptor distribution in trophoblast and attenuated proliferation induced by IGF-I or IGF-II (Ki67; P < 0.05, n = 5). 25304981 6 18 dep inhibitors 1153:1162 arg1 deoxymannojirimycin 1197:1215 deoxymannojirimycin 1197:1215 deoxymannojirimycin 1197:1215 Treatment of first trimester villous tissue explants with statins (pravastatin or cerivastatin) or inhibitors of N-glycosylation (tunicamycin, deoxymannojirimycin or castanospermine) altered receptor distribution in trophoblast and attenuated proliferation induced by IGF-I or IGF-II (Ki67; P < 0.05, n = 5). 25304981 6 18 dep inhibitors 1153:1162 arg1 tunicamycin 1184:1194 tunicamycin 1184:1194 tunicamycin 1184:1194 Treatment of first trimester villous tissue explants with statins (pravastatin or cerivastatin) or inhibitors of N-glycosylation (tunicamycin, deoxymannojirimycin or castanospermine) altered receptor distribution in trophoblast and attenuated proliferation induced by IGF-I or IGF-II (Ki67; P < 0.05, n = 5). 25304981 6 18 dep inhibitors 1153:1162 arg1 inhibitors 1153:1162 inhibitors 1153:1162 inhibitors of N-glycosylation (tunicamycin, deoxymannojirimycin or castanospermine) 1153:1235 Treatment of first trimester villous tissue explants with statins (pravastatin or cerivastatin) or inhibitors of N-glycosylation (tunicamycin, deoxymannojirimycin or castanospermine) altered receptor distribution in trophoblast and attenuated proliferation induced by IGF-I or IGF-II (Ki67; P < 0.05, n = 5). 25304981 0 19 theme receptor 119:126 arg1 glycosylation 128:140 insulin-like growth factor 1 receptor glycosylation 90:140 insulin-like growth factor 1 receptor glycosylation 90:140 Statins inhibit insulin-like growth factor action in first trimester placenta by altering insulin-like growth factor 1 receptor glycosylation. 25304981 6 20 dep Ki67 1339:1342 arg1 < 1347:1347 P < 0.05 1345:1352 P < 0.05 1345:1352 Treatment of first trimester villous tissue explants with statins (pravastatin or cerivastatin) or inhibitors of N-glycosylation (tunicamycin, deoxymannojirimycin or castanospermine) altered receptor distribution in trophoblast and attenuated proliferation induced by IGF-I or IGF-II (Ki67; P < 0.05, n = 5). 25304981 6 20 dep Ki67 1339:1342 arg1 n 1355:1355 n = 5 1355:1359 n = 5 1355:1359 Treatment of first trimester villous tissue explants with statins (pravastatin or cerivastatin) or inhibitors of N-glycosylation (tunicamycin, deoxymannojirimycin or castanospermine) altered receptor distribution in trophoblast and attenuated proliferation induced by IGF-I or IGF-II (Ki67; P < 0.05, n = 5). 25304981 9 21 link N-linked 1889:1896 arg1 glycosylation 1898:1910 N-linked glycosylation 1889:1910 N-linked glycosylation 1889:1910 These data suggest that statins attenuate IGF actions in the placenta by inhibiting N-linked glycosylation and subsequent expression of mature IGF1R at the placental cell surface. 25304981 4 22 link N-linked 834:841 arg1 glycans 843:849 N-linked glycans 834:849 N-linked glycans in the IGF receptor, IGF1R, 834:877 N-linked glycans in the IGF receptor, IGF1R, influence its presentation at the cell surface. 25304981 3 23 theme trophoblast 781:791 arg1 proliferation 793:805 trophoblast proliferation 781:805 trophoblast proliferation 781:805 We have previously shown that exposure of placental tissue to statins inhibits the action of insulin-like growth factors (IGF)-I and -II which are key regulators of trophoblast proliferation and placental development. 25304981 2 24 theme evolving 497:504 arg1 profile 518:524 the evolving demographic profile 493:524 the evolving demographic profile of these conditions 493:544 Affected individuals are often treated with statins (3-hydroxy-3-methylglutaryl co-enzyme A [HMG CoA] reductase inhibitors) to reduce circulating cholesterol levels and the risk of developing cardiovascular disease; given the evolving demographic profile of these conditions, such drugs are increasingly prescribed to women of reproductive age. 25304981 0 25 theme trimester 59:67 arg1 placenta 69:76 first trimester placenta 53:76 first trimester placenta 53:76 Statins inhibit insulin-like growth factor action in first trimester placenta by altering insulin-like growth factor 1 receptor glycosylation. 25304981 3 26 theme development 821:831 arg1 regulators 767:776 key regulators 763:776 key regulators of trophoblast proliferation and placental development 763:831 We have previously shown that exposure of placental tissue to statins inhibits the action of insulin-like growth factors (IGF)-I and -II which are key regulators of trophoblast proliferation and placental development. 25304981 3 26 theme development 821:831 arg1 factors 729:735 insulin-like growth factors 709:735 insulin-like growth factors (IGF)-I and -II which are key regulators of trophoblast proliferation and placental development 709:831 We have previously shown that exposure of placental tissue to statins inhibits the action of insulin-like growth factors (IGF)-I and -II which are key regulators of trophoblast proliferation and placental development. 25304981 6 27 theme = 1357:1357 arg1 n 1355:1355 n = 5 1355:1359 n = 5 1355:1359 Treatment of first trimester villous tissue explants with statins (pravastatin or cerivastatin) or inhibitors of N-glycosylation (tunicamycin, deoxymannojirimycin or castanospermine) altered receptor distribution in trophoblast and attenuated proliferation induced by IGF-I or IGF-II (Ki67; P < 0.05, n = 5). 25304981 0 28 theme insulin-like 90:101 arg1 factor 110:115 insulin-like growth factor 1 90:117 insulin-like growth factor 1 receptor glycosylation 90:140 Statins inhibit insulin-like growth factor action in first trimester placenta by altering insulin-like growth factor 1 receptor glycosylation. 25304981 8 29 with Co-incubation 1541:1553 arg1 statins 1579:1585 statins 1579:1585 statins 1579:1585 Co-incubation of tissue explants with statins and farnesyl pyrophosphate (which increases the supply of dolichol intermediates), prevented statin-mediated disruption of IGF1R localization and reversed the negative effect on IGF-mediated trophoblast proliferation. 25304981 8 29 with Co-incubation 1541:1553 arg1 pyrophosphate 1600:1612 farnesyl pyrophosphate 1591:1612 farnesyl pyrophosphate 1591:1612 Co-incubation of tissue explants with statins and farnesyl pyrophosphate (which increases the supply of dolichol intermediates), prevented statin-mediated disruption of IGF1R localization and reversed the negative effect on IGF-mediated trophoblast proliferation. 25304981 0 30 theme factor 110:115 arg1 glycosylation 128:140 insulin-like growth factor 1 receptor glycosylation 90:140 insulin-like growth factor 1 receptor glycosylation 90:140 Statins inhibit insulin-like growth factor action in first trimester placenta by altering insulin-like growth factor 1 receptor glycosylation. 25304981 4 31 from glycans 843:849 arg1 receptor 862:869 the IGF receptor 854:869 the IGF receptor 854:869 N-linked glycans in the IGF receptor, IGF1R, influence its presentation at the cell surface. 25304981 4 31 from glycans 843:849 arg1 IGF1R 872:876 IGF1R 872:876 IGF1R 872:876 N-linked glycans in the IGF receptor, IGF1R, influence its presentation at the cell surface. 25304981 2 32 theme reductase 373:381 arg1 inhibitors 383:392 3-hydroxy-3-methylglutaryl co-enzyme A [HMG CoA] reductase inhibitors 324:392 3-hydroxy-3-methylglutaryl co-enzyme A [HMG CoA] reductase inhibitors 324:392 Affected individuals are often treated with statins (3-hydroxy-3-methylglutaryl co-enzyme A [HMG CoA] reductase inhibitors) to reduce circulating cholesterol levels and the risk of developing cardiovascular disease; given the evolving demographic profile of these conditions, such drugs are increasingly prescribed to women of reproductive age. 25304981 2 32 theme reductase 373:381 arg1 statins 315:321 statins 315:321 statins (3-hydroxy-3-methylglutaryl co-enzyme A [HMG CoA] reductase inhibitors) 315:393 Affected individuals are often treated with statins (3-hydroxy-3-methylglutaryl co-enzyme A [HMG CoA] reductase inhibitors) to reduce circulating cholesterol levels and the risk of developing cardiovascular disease; given the evolving demographic profile of these conditions, such drugs are increasingly prescribed to women of reproductive age. 25304981 1 33 theme Western 256:262 arg1 world 264:268 the Western world 252:268 the Western world 252:268 The rapid rise in obesity, metabolic syndrome and type 2 diabetes is one of the major healthcare problems of the Western world. 25304981 9 34 gly glycosylation 1898:1910 arg1 surface 1976:1982 the placental cell surface 1957:1982 the placental cell surface 1957:1982 These data suggest that statins attenuate IGF actions in the placenta by inhibiting N-linked glycosylation and subsequent expression of mature IGF1R at the placental cell surface. 25304981 9 34 gly glycosylation 1898:1910 arg1 IGF1R 1948:1952 mature IGF1R 1941:1952 mature IGF1R 1941:1952 These data suggest that statins attenuate IGF actions in the placenta by inhibiting N-linked glycosylation and subsequent expression of mature IGF1R at the placental cell surface. 25304981 8 35 theme tissue 1558:1563 arg1 explants 1565:1572 tissue explants 1558:1572 tissue explants 1558:1572 Co-incubation of tissue explants with statins and farnesyl pyrophosphate (which increases the supply of dolichol intermediates), prevented statin-mediated disruption of IGF1R localization and reversed the negative effect on IGF-mediated trophoblast proliferation. 25304981 2 36 theme cholesterol 417:427 arg1 levels 429:434 circulating cholesterol levels 405:434 circulating cholesterol levels 405:434 Affected individuals are often treated with statins (3-hydroxy-3-methylglutaryl co-enzyme A [HMG CoA] reductase inhibitors) to reduce circulating cholesterol levels and the risk of developing cardiovascular disease; given the evolving demographic profile of these conditions, such drugs are increasingly prescribed to women of reproductive age. 25304981 0 37 theme insulin-like 16:27 arg1 factor 36:41 insulin-like growth factor 16:41 insulin-like growth factor action 16:48 Statins inhibit insulin-like growth factor action in first trimester placenta by altering insulin-like growth factor 1 receptor glycosylation. 25304981 8 38 from effect 1755:1760 arg1 proliferation 1790:1802 IGF-mediated trophoblast proliferation 1765:1802 IGF-mediated trophoblast proliferation 1765:1802 Co-incubation of tissue explants with statins and farnesyl pyrophosphate (which increases the supply of dolichol intermediates), prevented statin-mediated disruption of IGF1R localization and reversed the negative effect on IGF-mediated trophoblast proliferation. 25304981 0 39 theme factor 36:41 arg1 action 43:48 insulin-like growth factor action 16:48 insulin-like growth factor action 16:48 Statins inhibit insulin-like growth factor action in first trimester placenta by altering insulin-like growth factor 1 receptor glycosylation. 25304981 7 40 theme glycans 1532:1538 arg1 levels 1505:1510 reduced levels 1497:1510 reduced levels of complex N-linked glycans 1497:1538 Decreased binding of Phaseolus vulgaris lectin and phytohaemagglutinin to IGF1R immunoprecipitated from treated explants demonstrated reduced levels of complex N-linked glycans. 25304981 9 41 theme N-linked 1889:1896 arg1 glycosylation 1898:1910 N-linked glycosylation 1889:1910 N-linked glycosylation 1889:1910 These data suggest that statins attenuate IGF actions in the placenta by inhibiting N-linked glycosylation and subsequent expression of mature IGF1R at the placental cell surface. 25304981 2 42 theme 3-hydroxy-3-methylglutaryl 324:349 arg1 inhibitors 383:392 3-hydroxy-3-methylglutaryl co-enzyme A [HMG CoA] reductase inhibitors 324:392 3-hydroxy-3-methylglutaryl co-enzyme A [HMG CoA] reductase inhibitors 324:392 Affected individuals are often treated with statins (3-hydroxy-3-methylglutaryl co-enzyme A [HMG CoA] reductase inhibitors) to reduce circulating cholesterol levels and the risk of developing cardiovascular disease; given the evolving demographic profile of these conditions, such drugs are increasingly prescribed to women of reproductive age. 25304981 2 42 theme 3-hydroxy-3-methylglutaryl 324:349 arg1 statins 315:321 statins 315:321 statins (3-hydroxy-3-methylglutaryl co-enzyme A [HMG CoA] reductase inhibitors) 315:393 Affected individuals are often treated with statins (3-hydroxy-3-methylglutaryl co-enzyme A [HMG CoA] reductase inhibitors) to reduce circulating cholesterol levels and the risk of developing cardiovascular disease; given the evolving demographic profile of these conditions, such drugs are increasingly prescribed to women of reproductive age. 25304981 3 43 dep factors 729:735 arg1 -I 742:743 -I 742:743 -I 742:743 We have previously shown that exposure of placental tissue to statins inhibits the action of insulin-like growth factors (IGF)-I and -II which are key regulators of trophoblast proliferation and placental development. 25304981 3 43 dep factors 729:735 arg1 factors 729:735 insulin-like growth factors 709:735 insulin-like growth factors (IGF)-I and -II which are key regulators of trophoblast proliferation and placental development 709:831 We have previously shown that exposure of placental tissue to statins inhibits the action of insulin-like growth factors (IGF)-I and -II which are key regulators of trophoblast proliferation and placental development. 25304981 3 43 dep factors 729:735 arg1 -II 749:751 -II 749:751 -II 749:751 We have previously shown that exposure of placental tissue to statins inhibits the action of insulin-like growth factors (IGF)-I and -II which are key regulators of trophoblast proliferation and placental development. 25304981 7 44 theme complex 1515:1521 arg1 glycans 1532:1538 complex N-linked glycans 1515:1538 complex N-linked glycans 1515:1538 Decreased binding of Phaseolus vulgaris lectin and phytohaemagglutinin to IGF1R immunoprecipitated from treated explants demonstrated reduced levels of complex N-linked glycans. 25304981 6 45 theme explants 1098:1105 arg1 Treatment 1054:1062 Treatment 1054:1062 Treatment of first trimester villous tissue explants with statins (pravastatin or cerivastatin) or inhibitors of N-glycosylation (tunicamycin, deoxymannojirimycin or castanospermine) 1054:1235 Treatment of first trimester villous tissue explants with statins (pravastatin or cerivastatin) or inhibitors of N-glycosylation (tunicamycin, deoxymannojirimycin or castanospermine) altered receptor distribution in trophoblast and attenuated proliferation induced by IGF-I or IGF-II (Ki67; P < 0.05, n = 5). 25304981 3 46 theme tissue 668:673 arg1 exposure 646:653 exposure 646:653 exposure of placental tissue to statins 646:684 We have previously shown that exposure of placental tissue to statins inhibits the action of insulin-like growth factors (IGF)-I and -II which are key regulators of trophoblast proliferation and placental development. 25304981 2 47 theme CoA 368:370 arg1 inhibitors 383:392 3-hydroxy-3-methylglutaryl co-enzyme A [HMG CoA] reductase inhibitors 324:392 3-hydroxy-3-methylglutaryl co-enzyme A [HMG CoA] reductase inhibitors 324:392 Affected individuals are often treated with statins (3-hydroxy-3-methylglutaryl co-enzyme A [HMG CoA] reductase inhibitors) to reduce circulating cholesterol levels and the risk of developing cardiovascular disease; given the evolving demographic profile of these conditions, such drugs are increasingly prescribed to women of reproductive age. 25304981 2 47 theme CoA 368:370 arg1 statins 315:321 statins 315:321 statins (3-hydroxy-3-methylglutaryl co-enzyme A [HMG CoA] reductase inhibitors) 315:393 Affected individuals are often treated with statins (3-hydroxy-3-methylglutaryl co-enzyme A [HMG CoA] reductase inhibitors) to reduce circulating cholesterol levels and the risk of developing cardiovascular disease; given the evolving demographic profile of these conditions, such drugs are increasingly prescribed to women of reproductive age. 25304981 8 48 theme statin-mediated 1680:1694 arg1 disruption 1696:1705 statin-mediated disruption 1680:1705 statin-mediated disruption of IGF1R localization 1680:1727 Co-incubation of tissue explants with statins and farnesyl pyrophosphate (which increases the supply of dolichol intermediates), prevented statin-mediated disruption of IGF1R localization and reversed the negative effect on IGF-mediated trophoblast proliferation. 25304981 6 49 theme villous 1083:1089 arg1 explants 1098:1105 first trimester villous tissue explants 1067:1105 first trimester villous tissue explants 1067:1105 Treatment of first trimester villous tissue explants with statins (pravastatin or cerivastatin) or inhibitors of N-glycosylation (tunicamycin, deoxymannojirimycin or castanospermine) altered receptor distribution in trophoblast and attenuated proliferation induced by IGF-I or IGF-II (Ki67; P < 0.05, n = 5). 25304981 9 50 theme mature 1941:1946 arg1 IGF1R 1948:1952 mature IGF1R 1941:1952 mature IGF1R 1941:1952 These data suggest that statins attenuate IGF actions in the placenta by inhibiting N-linked glycosylation and subsequent expression of mature IGF1R at the placental cell surface. 25304981 2 51 theme A 361:361 arg1 inhibitors 383:392 3-hydroxy-3-methylglutaryl co-enzyme A [HMG CoA] reductase inhibitors 324:392 3-hydroxy-3-methylglutaryl co-enzyme A [HMG CoA] reductase inhibitors 324:392 Affected individuals are often treated with statins (3-hydroxy-3-methylglutaryl co-enzyme A [HMG CoA] reductase inhibitors) to reduce circulating cholesterol levels and the risk of developing cardiovascular disease; given the evolving demographic profile of these conditions, such drugs are increasingly prescribed to women of reproductive age. 25304981 2 51 theme A 361:361 arg1 statins 315:321 statins 315:321 statins (3-hydroxy-3-methylglutaryl co-enzyme A [HMG CoA] reductase inhibitors) 315:393 Affected individuals are often treated with statins (3-hydroxy-3-methylglutaryl co-enzyme A [HMG CoA] reductase inhibitors) to reduce circulating cholesterol levels and the risk of developing cardiovascular disease; given the evolving demographic profile of these conditions, such drugs are increasingly prescribed to women of reproductive age. 25304981 1 52 theme healthcare 229:238 arg1 problems 240:247 the major healthcare problems 219:247 the major healthcare problems of the Western world 219:268 The rapid rise in obesity, metabolic syndrome and type 2 diabetes is one of the major healthcare problems of the Western world. 25304981 7 53 theme treated 1467:1473 arg1 explants 1475:1482 treated explants 1467:1482 treated explants 1467:1482 Decreased binding of Phaseolus vulgaris lectin and phytohaemagglutinin to IGF1R immunoprecipitated from treated explants demonstrated reduced levels of complex N-linked glycans. 25304981 2 54 theme reproductive 598:609 arg1 age 611:613 reproductive age 598:613 reproductive age 598:613 Affected individuals are often treated with statins (3-hydroxy-3-methylglutaryl co-enzyme A [HMG CoA] reductase inhibitors) to reduce circulating cholesterol levels and the risk of developing cardiovascular disease; given the evolving demographic profile of these conditions, such drugs are increasingly prescribed to women of reproductive age. 25304981 6 55 theme first 1067:1071 arg1 explants 1098:1105 first trimester villous tissue explants 1067:1105 first trimester villous tissue explants 1067:1105 Treatment of first trimester villous tissue explants with statins (pravastatin or cerivastatin) or inhibitors of N-glycosylation (tunicamycin, deoxymannojirimycin or castanospermine) altered receptor distribution in trophoblast and attenuated proliferation induced by IGF-I or IGF-II (Ki67; P < 0.05, n = 5). 25304981 2 56 theme Affected 271:278 arg1 individuals 280:290 Affected individuals 271:290 Affected individuals 271:290 Affected individuals are often treated with statins (3-hydroxy-3-methylglutaryl co-enzyme A [HMG CoA] reductase inhibitors) to reduce circulating cholesterol levels and the risk of developing cardiovascular disease; given the evolving demographic profile of these conditions, such drugs are increasingly prescribed to women of reproductive age. 25304981 8 57 theme localization 1716:1727 arg1 disruption 1696:1705 statin-mediated disruption 1680:1705 statin-mediated disruption of IGF1R localization 1680:1727 Co-incubation of tissue explants with statins and farnesyl pyrophosphate (which increases the supply of dolichol intermediates), prevented statin-mediated disruption of IGF1R localization and reversed the negative effect on IGF-mediated trophoblast proliferation. 25304981 7 58 theme phytohaemagglutinin 1414:1432 arg1 binding 1373:1379 Decreased binding 1363:1379 Decreased binding of Phaseolus vulgaris lectin and phytohaemagglutinin to IGF1R immunoprecipitated from treated explants 1363:1482 Decreased binding of Phaseolus vulgaris lectin and phytohaemagglutinin to IGF1R immunoprecipitated from treated explants demonstrated reduced levels of complex N-linked glycans. 25304981 9 59 theme placental 1961:1969 arg1 surface 1976:1982 the placental cell surface 1957:1982 the placental cell surface 1957:1982 These data suggest that statins attenuate IGF actions in the placenta by inhibiting N-linked glycosylation and subsequent expression of mature IGF1R at the placental cell surface. 25304981 8 60 theme intermediates 1654:1666 arg1 supply 1635:1640 the supply 1631:1640 the supply of dolichol intermediates 1631:1666 Co-incubation of tissue explants with statins and farnesyl pyrophosphate (which increases the supply of dolichol intermediates), prevented statin-mediated disruption of IGF1R localization and reversed the negative effect on IGF-mediated trophoblast proliferation. 25304981 4 61 theme N-linked 834:841 arg1 glycans 843:849 N-linked glycans 834:849 N-linked glycans in the IGF receptor, IGF1R, 834:877 N-linked glycans in the IGF receptor, IGF1R, influence its presentation at the cell surface. 25304981 3 62 theme growth 722:727 arg1 -I 742:743 -I 742:743 -I 742:743 We have previously shown that exposure of placental tissue to statins inhibits the action of insulin-like growth factors (IGF)-I and -II which are key regulators of trophoblast proliferation and placental development. 25304981 3 62 theme growth 722:727 arg1 IGF 738:740 IGF 738:740 IGF 738:740 We have previously shown that exposure of placental tissue to statins inhibits the action of insulin-like growth factors (IGF)-I and -II which are key regulators of trophoblast proliferation and placental development. 25304981 3 62 theme growth 722:727 arg1 factors 729:735 insulin-like growth factors 709:735 insulin-like growth factors (IGF)-I and -II which are key regulators of trophoblast proliferation and placental development 709:831 We have previously shown that exposure of placental tissue to statins inhibits the action of insulin-like growth factors (IGF)-I and -II which are key regulators of trophoblast proliferation and placental development. 25304981 3 62 theme growth 722:727 arg1 regulators 767:776 key regulators 763:776 key regulators of trophoblast proliferation and placental development 763:831 We have previously shown that exposure of placental tissue to statins inhibits the action of insulin-like growth factors (IGF)-I and -II which are key regulators of trophoblast proliferation and placental development. 25304981 3 62 theme growth 722:727 arg1 -II 749:751 -II 749:751 -II 749:751 We have previously shown that exposure of placental tissue to statins inhibits the action of insulin-like growth factors (IGF)-I and -II which are key regulators of trophoblast proliferation and placental development. 25304981 8 63 theme negative 1746:1753 arg1 effect 1755:1760 the negative effect 1742:1760 the negative effect on IGF-mediated trophoblast proliferation 1742:1802 Co-incubation of tissue explants with statins and farnesyl pyrophosphate (which increases the supply of dolichol intermediates), prevented statin-mediated disruption of IGF1R localization and reversed the negative effect on IGF-mediated trophoblast proliferation. 25304981 7 64 theme Phaseolus 1384:1392 arg1 vulgaris 1394:1401 Phaseolus vulgaris lectin and phytohaemagglutinin 1384:1432 vulgaris 1394:1401 Decreased binding of Phaseolus vulgaris lectin and phytohaemagglutinin to IGF1R immunoprecipitated from treated explants demonstrated reduced levels of complex N-linked glycans. 25304981 6 65 theme P 1345:1345 arg1 < 1347:1347 P < 0.05 1345:1352 P < 0.05 1345:1352 Treatment of first trimester villous tissue explants with statins (pravastatin or cerivastatin) or inhibitors of N-glycosylation (tunicamycin, deoxymannojirimycin or castanospermine) altered receptor distribution in trophoblast and attenuated proliferation induced by IGF-I or IGF-II (Ki67; P < 0.05, n = 5). 25304981 1 66 theme type 193:196 arg1 diabetes 200:207 type 2 diabetes 193:207 type 2 diabetes 193:207 The rapid rise in obesity, metabolic syndrome and type 2 diabetes is one of the major healthcare problems of the Western world. 25304981 2 67 theme such 547:550 arg1 drugs 552:556 such drugs 547:556 such drugs 547:556 Affected individuals are often treated with statins (3-hydroxy-3-methylglutaryl co-enzyme A [HMG CoA] reductase inhibitors) to reduce circulating cholesterol levels and the risk of developing cardiovascular disease; given the evolving demographic profile of these conditions, such drugs are increasingly prescribed to women of reproductive age. 25304981 8 68 theme trophoblast 1778:1788 arg1 proliferation 1790:1802 IGF-mediated trophoblast proliferation 1765:1802 IGF-mediated trophoblast proliferation 1765:1802 Co-incubation of tissue explants with statins and farnesyl pyrophosphate (which increases the supply of dolichol intermediates), prevented statin-mediated disruption of IGF1R localization and reversed the negative effect on IGF-mediated trophoblast proliferation. 25304981 4 69 theme cell 913:916 arg1 surface 918:924 the cell surface 909:924 the cell surface 909:924 N-linked glycans in the IGF receptor, IGF1R, influence its presentation at the cell surface. 25304981 3 70 theme key 763:765 arg1 regulators 767:776 key regulators 763:776 key regulators of trophoblast proliferation and placental development 763:831 We have previously shown that exposure of placental tissue to statins inhibits the action of insulin-like growth factors (IGF)-I and -II which are key regulators of trophoblast proliferation and placental development. 25304981 3 70 theme key 763:765 arg1 factors 729:735 insulin-like growth factors 709:735 insulin-like growth factors (IGF)-I and -II which are key regulators of trophoblast proliferation and placental development 709:831 We have previously shown that exposure of placental tissue to statins inhibits the action of insulin-like growth factors (IGF)-I and -II which are key regulators of trophoblast proliferation and placental development. 25304981 7 71 dep vulgaris 1394:1401 arg1 lectin 1403:1408 lectin 1403:1408 lectin 1403:1408 Decreased binding of Phaseolus vulgaris lectin and phytohaemagglutinin to IGF1R immunoprecipitated from treated explants demonstrated reduced levels of complex N-linked glycans. 25304981 5 72 theme IGF1R 1026:1030 arg1 function 1032:1039 IGF1R function 1026:1039 IGF1R function 1026:1039 This study aimed to determine whether statins, which are known to affect N-glycosylation, modulate IGF1R function in placenta. 25304981 3 73 theme proliferation 793:805 arg1 regulators 767:776 key regulators 763:776 key regulators of trophoblast proliferation and placental development 763:831 We have previously shown that exposure of placental tissue to statins inhibits the action of insulin-like growth factors (IGF)-I and -II which are key regulators of trophoblast proliferation and placental development. 25304981 3 73 theme proliferation 793:805 arg1 factors 729:735 insulin-like growth factors 709:735 insulin-like growth factors (IGF)-I and -II which are key regulators of trophoblast proliferation and placental development 709:831 We have previously shown that exposure of placental tissue to statins inhibits the action of insulin-like growth factors (IGF)-I and -II which are key regulators of trophoblast proliferation and placental development. 25304981 1 74 theme rapid 147:151 arg1 rise 153:156 The rapid rise 143:156 The rapid rise in obesity, metabolic syndrome and type 2 diabetes 143:207 The rapid rise in obesity, metabolic syndrome and type 2 diabetes is one of the major healthcare problems of the Western world. 25304981 1 74 theme rapid 147:151 arg1 one 212:214 one 212:214 one 212:214 The rapid rise in obesity, metabolic syndrome and type 2 diabetes is one of the major healthcare problems of the Western world. 25304981 1 74 theme rapid 147:151 arg1 problems 240:247 the major healthcare problems 219:247 the major healthcare problems of the Western world 219:268 The rapid rise in obesity, metabolic syndrome and type 2 diabetes is one of the major healthcare problems of the Western world. 25304981 0 75 theme growth 103:108 arg1 factor 110:115 insulin-like growth factor 1 90:117 insulin-like growth factor 1 receptor glycosylation 90:140 Statins inhibit insulin-like growth factor action in first trimester placenta by altering insulin-like growth factor 1 receptor glycosylation. 25304981 3 76 theme placental 811:819 arg1 development 821:831 placental development 811:831 placental development 811:831 We have previously shown that exposure of placental tissue to statins inhibits the action of insulin-like growth factors (IGF)-I and -II which are key regulators of trophoblast proliferation and placental development. 25304981 1 77 from rise 153:156 arg1 syndrome 180:187 metabolic syndrome 170:187 metabolic syndrome 170:187 The rapid rise in obesity, metabolic syndrome and type 2 diabetes is one of the major healthcare problems of the Western world. 25304981 1 77 from rise 153:156 arg1 diabetes 200:207 type 2 diabetes 193:207 type 2 diabetes 193:207 The rapid rise in obesity, metabolic syndrome and type 2 diabetes is one of the major healthcare problems of the Western world. 25304981 1 77 from rise 153:156 arg1 obesity 161:167 obesity 161:167 obesity 161:167 The rapid rise in obesity, metabolic syndrome and type 2 diabetes is one of the major healthcare problems of the Western world. 25304981 2 78 theme demographic 506:516 arg1 profile 518:524 the evolving demographic profile 493:524 the evolving demographic profile of these conditions 493:544 Affected individuals are often treated with statins (3-hydroxy-3-methylglutaryl co-enzyme A [HMG CoA] reductase inhibitors) to reduce circulating cholesterol levels and the risk of developing cardiovascular disease; given the evolving demographic profile of these conditions, such drugs are increasingly prescribed to women of reproductive age. 25304981 8 79 theme explants 1565:1572 arg1 Co-incubation 1541:1553 Co-incubation 1541:1553 Co-incubation of tissue explants with statins and farnesyl pyrophosphate (which increases the supply of dolichol intermediates), 1541:1668 Co-incubation of tissue explants with statins and farnesyl pyrophosphate (which increases the supply of dolichol intermediates), prevented statin-mediated disruption of IGF1R localization and reversed the negative effect on IGF-mediated trophoblast proliferation. 25304981 0 80 theme growth 29:34 arg1 factor 36:41 insulin-like growth factor 16:41 insulin-like growth factor action 16:48 Statins inhibit insulin-like growth factor action in first trimester placenta by altering insulin-like growth factor 1 receptor glycosylation. 25304981 1 81 theme world 264:268 arg1 problems 240:247 the major healthcare problems 219:247 the major healthcare problems of the Western world 219:268 The rapid rise in obesity, metabolic syndrome and type 2 diabetes is one of the major healthcare problems of the Western world. 25304981 2 82 theme circulating 405:415 arg1 levels 429:434 circulating cholesterol levels 405:434 circulating cholesterol levels 405:434 Affected individuals are often treated with statins (3-hydroxy-3-methylglutaryl co-enzyme A [HMG CoA] reductase inhibitors) to reduce circulating cholesterol levels and the risk of developing cardiovascular disease; given the evolving demographic profile of these conditions, such drugs are increasingly prescribed to women of reproductive age. 25304981 2 83 theme cardiovascular 463:476 arg1 disease 478:484 cardiovascular disease 463:484 cardiovascular disease 463:484 Affected individuals are often treated with statins (3-hydroxy-3-methylglutaryl co-enzyme A [HMG CoA] reductase inhibitors) to reduce circulating cholesterol levels and the risk of developing cardiovascular disease; given the evolving demographic profile of these conditions, such drugs are increasingly prescribed to women of reproductive age. 25304981 8 84 theme farnesyl 1591:1598 arg1 pyrophosphate 1600:1612 farnesyl pyrophosphate 1591:1612 farnesyl pyrophosphate 1591:1612 Co-incubation of tissue explants with statins and farnesyl pyrophosphate (which increases the supply of dolichol intermediates), prevented statin-mediated disruption of IGF1R localization and reversed the negative effect on IGF-mediated trophoblast proliferation. 25304981 9 85 theme IGF 1847:1849 arg1 actions 1851:1857 IGF actions 1847:1857 IGF actions 1847:1857 These data suggest that statins attenuate IGF actions in the placenta by inhibiting N-linked glycosylation and subsequent expression of mature IGF1R at the placental cell surface. 25304981 0 86 theme first 53:57 arg1 placenta 69:76 first trimester placenta 53:76 first trimester placenta 53:76 Statins inhibit insulin-like growth factor action in first trimester placenta by altering insulin-like growth factor 1 receptor glycosylation. 25304981 6 87 with Treatment 1054:1062 arg1 deoxymannojirimycin 1197:1215 deoxymannojirimycin 1197:1215 deoxymannojirimycin 1197:1215 Treatment of first trimester villous tissue explants with statins (pravastatin or cerivastatin) or inhibitors of N-glycosylation (tunicamycin, deoxymannojirimycin or castanospermine) altered receptor distribution in trophoblast and attenuated proliferation induced by IGF-I or IGF-II (Ki67; P < 0.05, n = 5). 25304981 6 87 with Treatment 1054:1062 arg1 statins 1112:1118 statins 1112:1118 statins (pravastatin or cerivastatin) 1112:1148 Treatment of first trimester villous tissue explants with statins (pravastatin or cerivastatin) or inhibitors of N-glycosylation (tunicamycin, deoxymannojirimycin or castanospermine) altered receptor distribution in trophoblast and attenuated proliferation induced by IGF-I or IGF-II (Ki67; P < 0.05, n = 5). 25304981 6 87 with Treatment 1054:1062 arg1 inhibitors 1153:1162 inhibitors 1153:1162 inhibitors of N-glycosylation (tunicamycin, deoxymannojirimycin or castanospermine) 1153:1235 Treatment of first trimester villous tissue explants with statins (pravastatin or cerivastatin) or inhibitors of N-glycosylation (tunicamycin, deoxymannojirimycin or castanospermine) altered receptor distribution in trophoblast and attenuated proliferation induced by IGF-I or IGF-II (Ki67; P < 0.05, n = 5). 25304981 6 87 with Treatment 1054:1062 arg1 castanospermine 1220:1234 castanospermine 1220:1234 castanospermine 1220:1234 Treatment of first trimester villous tissue explants with statins (pravastatin or cerivastatin) or inhibitors of N-glycosylation (tunicamycin, deoxymannojirimycin or castanospermine) altered receptor distribution in trophoblast and attenuated proliferation induced by IGF-I or IGF-II (Ki67; P < 0.05, n = 5). 25304981 6 87 with Treatment 1054:1062 arg1 pravastatin 1121:1131 pravastatin 1121:1131 pravastatin 1121:1131 Treatment of first trimester villous tissue explants with statins (pravastatin or cerivastatin) or inhibitors of N-glycosylation (tunicamycin, deoxymannojirimycin or castanospermine) altered receptor distribution in trophoblast and attenuated proliferation induced by IGF-I or IGF-II (Ki67; P < 0.05, n = 5). 25304981 6 87 with Treatment 1054:1062 arg1 cerivastatin 1136:1147 cerivastatin 1136:1147 cerivastatin 1136:1147 Treatment of first trimester villous tissue explants with statins (pravastatin or cerivastatin) or inhibitors of N-glycosylation (tunicamycin, deoxymannojirimycin or castanospermine) altered receptor distribution in trophoblast and attenuated proliferation induced by IGF-I or IGF-II (Ki67; P < 0.05, n = 5). 25304981 6 87 with Treatment 1054:1062 arg1 tunicamycin 1184:1194 tunicamycin 1184:1194 tunicamycin 1184:1194 Treatment of first trimester villous tissue explants with statins (pravastatin or cerivastatin) or inhibitors of N-glycosylation (tunicamycin, deoxymannojirimycin or castanospermine) altered receptor distribution in trophoblast and attenuated proliferation induced by IGF-I or IGF-II (Ki67; P < 0.05, n = 5). 25304981 2 88 theme conditions 535:544 arg1 profile 518:524 the evolving demographic profile 493:524 the evolving demographic profile of these conditions 493:544 Affected individuals are often treated with statins (3-hydroxy-3-methylglutaryl co-enzyme A [HMG CoA] reductase inhibitors) to reduce circulating cholesterol levels and the risk of developing cardiovascular disease; given the evolving demographic profile of these conditions, such drugs are increasingly prescribed to women of reproductive age. 25304981 7 89 theme N-linked 1523:1530 arg1 glycans 1532:1538 complex N-linked glycans 1515:1538 complex N-linked glycans 1515:1538 Decreased binding of Phaseolus vulgaris lectin and phytohaemagglutinin to IGF1R immunoprecipitated from treated explants demonstrated reduced levels of complex N-linked glycans. 25304981 9 90 theme subsequent 1916:1925 arg1 expression 1927:1936 subsequent expression 1916:1936 subsequent expression 1916:1936 These data suggest that statins attenuate IGF actions in the placenta by inhibiting N-linked glycosylation and subsequent expression of mature IGF1R at the placental cell surface. 25304981 3 91 theme placental 658:666 arg1 tissue 668:673 placental tissue 658:673 placental tissue 658:673 We have previously shown that exposure of placental tissue to statins inhibits the action of insulin-like growth factors (IGF)-I and -II which are key regulators of trophoblast proliferation and placental development. 25304981 6 92 theme tissue 1091:1096 arg1 explants 1098:1105 first trimester villous tissue explants 1067:1105 first trimester villous tissue explants 1067:1105 Treatment of first trimester villous tissue explants with statins (pravastatin or cerivastatin) or inhibitors of N-glycosylation (tunicamycin, deoxymannojirimycin or castanospermine) altered receptor distribution in trophoblast and attenuated proliferation induced by IGF-I or IGF-II (Ki67; P < 0.05, n = 5). 25304981 7 93 link N-linked 1523:1530 arg1 glycans 1532:1538 complex N-linked glycans 1515:1538 complex N-linked glycans 1515:1538 Decreased binding of Phaseolus vulgaris lectin and phytohaemagglutinin to IGF1R immunoprecipitated from treated explants demonstrated reduced levels of complex N-linked glycans. 25304981 6 94 dep statins 1112:1118 arg1 cerivastatin 1136:1147 cerivastatin 1136:1147 cerivastatin 1136:1147 Treatment of first trimester villous tissue explants with statins (pravastatin or cerivastatin) or inhibitors of N-glycosylation (tunicamycin, deoxymannojirimycin or castanospermine) altered receptor distribution in trophoblast and attenuated proliferation induced by IGF-I or IGF-II (Ki67; P < 0.05, n = 5). 25304981 6 94 dep statins 1112:1118 arg1 pravastatin 1121:1131 pravastatin 1121:1131 pravastatin 1121:1131 Treatment of first trimester villous tissue explants with statins (pravastatin or cerivastatin) or inhibitors of N-glycosylation (tunicamycin, deoxymannojirimycin or castanospermine) altered receptor distribution in trophoblast and attenuated proliferation induced by IGF-I or IGF-II (Ki67; P < 0.05, n = 5). 25304981 6 94 dep statins 1112:1118 arg1 statins 1112:1118 statins 1112:1118 statins (pravastatin or cerivastatin) 1112:1148 Treatment of first trimester villous tissue explants with statins (pravastatin or cerivastatin) or inhibitors of N-glycosylation (tunicamycin, deoxymannojirimycin or castanospermine) altered receptor distribution in trophoblast and attenuated proliferation induced by IGF-I or IGF-II (Ki67; P < 0.05, n = 5). 25304981 2 95 theme [HMG 363:366 arg1 inhibitors 383:392 3-hydroxy-3-methylglutaryl co-enzyme A [HMG CoA] reductase inhibitors 324:392 3-hydroxy-3-methylglutaryl co-enzyme A [HMG CoA] reductase inhibitors 324:392 Affected individuals are often treated with statins (3-hydroxy-3-methylglutaryl co-enzyme A [HMG CoA] reductase inhibitors) to reduce circulating cholesterol levels and the risk of developing cardiovascular disease; given the evolving demographic profile of these conditions, such drugs are increasingly prescribed to women of reproductive age. 25304981 2 95 theme [HMG 363:366 arg1 statins 315:321 statins 315:321 statins (3-hydroxy-3-methylglutaryl co-enzyme A [HMG CoA] reductase inhibitors) 315:393 Affected individuals are often treated with statins (3-hydroxy-3-methylglutaryl co-enzyme A [HMG CoA] reductase inhibitors) to reduce circulating cholesterol levels and the risk of developing cardiovascular disease; given the evolving demographic profile of these conditions, such drugs are increasingly prescribed to women of reproductive age. 25304981 8 96 theme IGF1R 1710:1714 arg1 localization 1716:1727 IGF1R localization 1710:1727 IGF1R localization 1710:1727 Co-incubation of tissue explants with statins and farnesyl pyrophosphate (which increases the supply of dolichol intermediates), prevented statin-mediated disruption of IGF1R localization and reversed the negative effect on IGF-mediated trophoblast proliferation. 25304981 1 97 theme major 223:227 arg1 problems 240:247 the major healthcare problems 219:247 the major healthcare problems of the Western world 219:268 The rapid rise in obesity, metabolic syndrome and type 2 diabetes is one of the major healthcare problems of the Western world. 28477486 3 0 theme photoelectron 601:613 arg1 spectroscopy 615:626 X-ray photoelectron spectroscopy 595:626 X-ray photoelectron spectroscopy 595:626 Immunoblotting (using Pla a 1 and Pla a 2 antibodies), infrared and X-ray photoelectron spectroscopy techniques were used. 28477486 5 1 theme XPS 1081:1083 arg1 1s 1122:1123 high-resolution components C 1s 1093:1123 high-resolution components C 1s 1093:1123 The spectroscopy results showed modifications in the FTIR spectral features of bands assigned to proteins, lipids, and polysaccharides of the pollen exposed to the pollutants, as well as in the XPS spectra high-resolution components C 1s, N 1s, and O 1s. 28477486 5 1 theme XPS 1081:1083 arg1 1s 1128:1129 N 1s 1126:1129 N 1s 1126:1129 The spectroscopy results showed modifications in the FTIR spectral features of bands assigned to proteins, lipids, and polysaccharides of the pollen exposed to the pollutants, as well as in the XPS spectra high-resolution components C 1s, N 1s, and O 1s. 28477486 5 1 theme XPS 1081:1083 arg1 spectra 1085:1091 the XPS spectra high-resolution components C 1s, N 1s, and O 1s 1077:1139 the XPS spectra high-resolution components C 1s, N 1s, and O 1s 1077:1139 The spectroscopy results showed modifications in the FTIR spectral features of bands assigned to proteins, lipids, and polysaccharides of the pollen exposed to the pollutants, as well as in the XPS spectra high-resolution components C 1s, N 1s, and O 1s. 28477486 5 1 theme XPS 1081:1083 arg1 1s 1138:1139 O 1s 1136:1139 O 1s 1136:1139 The spectroscopy results showed modifications in the FTIR spectral features of bands assigned to proteins, lipids, and polysaccharides of the pollen exposed to the pollutants, as well as in the XPS spectra high-resolution components C 1s, N 1s, and O 1s. 28477486 0 2 theme acerifolia 58:67 arg1 pollen 69:74 Platanus x acerifolia pollen 47:74 Platanus x acerifolia pollen 47:74 Effect of O3 and NO2 atmospheric pollutants on Platanus x acerifolia pollen: Immunochemical and spectroscopic analysis. 28477486 2 3 dep levels 426:431 arg1 O3 434:435 O3 434:435 O3: 0.061ppm; NO2: 0.025ppm and the mixture of O3 and NO2: 0.060 and 0.031ppm respectively 434:523 Pollen samples were subjected to O3 and/or NO2 under in vitro conditions for 6h at atmospheric concentration levels (O3: 0.061ppm; NO2: 0.025ppm and the mixture of O3 and NO2: 0.060 and 0.031ppm respectively). 28477486 3 4 theme Pla 561:563 arg1 a 565:565 Pla a 2 561:567 Pla a 2 561:567 Immunoblotting (using Pla a 1 and Pla a 2 antibodies), infrared and X-ray photoelectron spectroscopy techniques were used. 28477486 0 5 from Effect 0:5 arg1 pollen 69:74 Platanus x acerifolia pollen 47:74 Platanus x acerifolia pollen 47:74 Effect of O3 and NO2 atmospheric pollutants on Platanus x acerifolia pollen: Immunochemical and spectroscopic analysis. 28477486 4 6 theme pollen 686:691 arg1 changes 707:713 pollen allergenicity changes 686:713 pollen allergenicity changes 686:713 Immunochemical analysis showed that pollen allergenicity changes were different according to the pollutant tested (gas or mixture of gasses) and that the same pollutant gas may interact in a different manner with each specific allergen. 28477486 5 7 theme O 1136:1136 arg1 spectra 1085:1091 the XPS spectra high-resolution components C 1s, N 1s, and O 1s 1077:1139 the XPS spectra high-resolution components C 1s, N 1s, and O 1s 1077:1139 The spectroscopy results showed modifications in the FTIR spectral features of bands assigned to proteins, lipids, and polysaccharides of the pollen exposed to the pollutants, as well as in the XPS spectra high-resolution components C 1s, N 1s, and O 1s. 28477486 5 7 theme O 1136:1136 arg1 1s 1138:1139 O 1s 1136:1139 O 1s 1136:1139 The spectroscopy results showed modifications in the FTIR spectral features of bands assigned to proteins, lipids, and polysaccharides of the pollen exposed to the pollutants, as well as in the XPS spectra high-resolution components C 1s, N 1s, and O 1s. 28477486 1 8 theme allergenic 224:233 arg1 properties 235:244 allergenic properties 224:244 allergenic properties 224:244 In the present study, the effects of two important oxidizing atmospheric pollutants (O3 and NO2) on the allergenic properties and chemical composition of Platanus x acerifolia pollen were studied. 28477486 4 9 theme different 841:849 arg1 manner 851:856 a different manner 839:856 a different manner 839:856 Immunochemical analysis showed that pollen allergenicity changes were different according to the pollutant tested (gas or mixture of gasses) and that the same pollutant gas may interact in a different manner with each specific allergen. 28477486 2 10 dep O3 434:435 arg1 mixture 470:476 the mixture 466:476 the mixture of O3 and NO2 466:490 Pollen samples were subjected to O3 and/or NO2 under in vitro conditions for 6h at atmospheric concentration levels (O3: 0.061ppm; NO2: 0.025ppm and the mixture of O3 and NO2: 0.060 and 0.031ppm respectively). 28477486 2 10 dep O3 434:435 arg1 0.060 493:497 0.060 493:497 0.060 493:497 Pollen samples were subjected to O3 and/or NO2 under in vitro conditions for 6h at atmospheric concentration levels (O3: 0.061ppm; NO2: 0.025ppm and the mixture of O3 and NO2: 0.060 and 0.031ppm respectively). 28477486 2 10 dep O3 434:435 arg1 0.061ppm 438:445 0.061ppm 438:445 O3: 0.061ppm; NO2: 0.025ppm and the mixture of O3 and NO2: 0.060 and 0.031ppm respectively 434:523 Pollen samples were subjected to O3 and/or NO2 under in vitro conditions for 6h at atmospheric concentration levels (O3: 0.061ppm; NO2: 0.025ppm and the mixture of O3 and NO2: 0.060 and 0.031ppm respectively). 28477486 2 10 dep O3 434:435 arg1 0.031ppm 503:510 0.031ppm 503:510 0.031ppm 503:510 Pollen samples were subjected to O3 and/or NO2 under in vitro conditions for 6h at atmospheric concentration levels (O3: 0.061ppm; NO2: 0.025ppm and the mixture of O3 and NO2: 0.060 and 0.031ppm respectively). 28477486 2 10 dep O3 434:435 arg1 NO2 448:450 NO2 448:450 O3: 0.061ppm; NO2: 0.025ppm and the mixture of O3 and NO2: 0.060 and 0.031ppm respectively 434:523 Pollen samples were subjected to O3 and/or NO2 under in vitro conditions for 6h at atmospheric concentration levels (O3: 0.061ppm; NO2: 0.025ppm and the mixture of O3 and NO2: 0.060 and 0.031ppm respectively). 28477486 2 10 dep O3 434:435 arg1 0.025ppm 453:460 0.025ppm 453:460 0.025ppm 453:460 Pollen samples were subjected to O3 and/or NO2 under in vitro conditions for 6h at atmospheric concentration levels (O3: 0.061ppm; NO2: 0.025ppm and the mixture of O3 and NO2: 0.060 and 0.031ppm respectively). 28477486 5 11 theme spectroscopy 891:902 arg1 results 904:910 The spectroscopy results 887:910 The spectroscopy results 887:910 The spectroscopy results showed modifications in the FTIR spectral features of bands assigned to proteins, lipids, and polysaccharides of the pollen exposed to the pollutants, as well as in the XPS spectra high-resolution components C 1s, N 1s, and O 1s. 28477486 5 12 theme components 1109:1118 arg1 1s 1122:1123 high-resolution components C 1s 1093:1123 high-resolution components C 1s 1093:1123 The spectroscopy results showed modifications in the FTIR spectral features of bands assigned to proteins, lipids, and polysaccharides of the pollen exposed to the pollutants, as well as in the XPS spectra high-resolution components C 1s, N 1s, and O 1s. 28477486 5 12 theme components 1109:1118 arg1 spectra 1085:1091 the XPS spectra high-resolution components C 1s, N 1s, and O 1s 1077:1139 the XPS spectra high-resolution components C 1s, N 1s, and O 1s 1077:1139 The spectroscopy results showed modifications in the FTIR spectral features of bands assigned to proteins, lipids, and polysaccharides of the pollen exposed to the pollutants, as well as in the XPS spectra high-resolution components C 1s, N 1s, and O 1s. 28477486 0 13 theme spectroscopic 96:108 arg1 analysis 110:117 spectroscopic analysis 96:117 spectroscopic analysis 96:117 Effect of O3 and NO2 atmospheric pollutants on Platanus x acerifolia pollen: Immunochemical and spectroscopic analysis. 28477486 2 14 from levels 426:431 arg1 6h 394:395 6h 394:395 6h at atmospheric concentration levels (O3: 0.061ppm; NO2: 0.025ppm and the mixture of O3 and NO2: 0.060 and 0.031ppm respectively) 394:524 Pollen samples were subjected to O3 and/or NO2 under in vitro conditions for 6h at atmospheric concentration levels (O3: 0.061ppm; NO2: 0.025ppm and the mixture of O3 and NO2: 0.060 and 0.031ppm respectively). 28477486 4 15 dep tested 757:762 arg1 mixture 772:778 gas or mixture 765:778 mixture 772:778 Immunochemical analysis showed that pollen allergenicity changes were different according to the pollutant tested (gas or mixture of gasses) and that the same pollutant gas may interact in a different manner with each specific allergen. 28477486 4 15 dep tested 757:762 arg1 gas 765:767 gas or mixture 765:778 gas 765:767 Immunochemical analysis showed that pollen allergenicity changes were different according to the pollutant tested (gas or mixture of gasses) and that the same pollutant gas may interact in a different manner with each specific allergen. 28477486 5 16 from modifications 919:931 arg1 1s 1122:1123 high-resolution components C 1s 1093:1123 high-resolution components C 1s 1093:1123 The spectroscopy results showed modifications in the FTIR spectral features of bands assigned to proteins, lipids, and polysaccharides of the pollen exposed to the pollutants, as well as in the XPS spectra high-resolution components C 1s, N 1s, and O 1s. 28477486 5 16 from modifications 919:931 arg1 features 954:961 the FTIR spectral features 936:961 the FTIR spectral features of bands assigned to proteins, lipids, and polysaccharides of the pollen exposed to the pollutants 936:1060 The spectroscopy results showed modifications in the FTIR spectral features of bands assigned to proteins, lipids, and polysaccharides of the pollen exposed to the pollutants, as well as in the XPS spectra high-resolution components C 1s, N 1s, and O 1s. 28477486 5 16 from modifications 919:931 arg1 1s 1128:1129 N 1s 1126:1129 N 1s 1126:1129 The spectroscopy results showed modifications in the FTIR spectral features of bands assigned to proteins, lipids, and polysaccharides of the pollen exposed to the pollutants, as well as in the XPS spectra high-resolution components C 1s, N 1s, and O 1s. 28477486 5 16 from modifications 919:931 arg1 spectra 1085:1091 the XPS spectra high-resolution components C 1s, N 1s, and O 1s 1077:1139 the XPS spectra high-resolution components C 1s, N 1s, and O 1s 1077:1139 The spectroscopy results showed modifications in the FTIR spectral features of bands assigned to proteins, lipids, and polysaccharides of the pollen exposed to the pollutants, as well as in the XPS spectra high-resolution components C 1s, N 1s, and O 1s. 28477486 5 16 from modifications 919:931 arg1 1s 1138:1139 O 1s 1136:1139 O 1s 1136:1139 The spectroscopy results showed modifications in the FTIR spectral features of bands assigned to proteins, lipids, and polysaccharides of the pollen exposed to the pollutants, as well as in the XPS spectra high-resolution components C 1s, N 1s, and O 1s. 28477486 5 17 theme high-resolution 1093:1107 arg1 components 1109:1118 high-resolution components 1093:1118 high-resolution components C 1s 1093:1123 The spectroscopy results showed modifications in the FTIR spectral features of bands assigned to proteins, lipids, and polysaccharides of the pollen exposed to the pollutants, as well as in the XPS spectra high-resolution components C 1s, N 1s, and O 1s. 28477486 6 18 theme further 1202:1208 arg1 modifications 1210:1222 further modifications 1202:1222 further modifications of its components induced by air pollution, which can compromise the pollen function 1202:1307 This indicates that while airborne, the pollen wall suffers further modifications of its components induced by air pollution, which can compromise the pollen function. 28477486 1 19 dep Platanus 274:281 arg1 pollen 296:301 pollen 296:301 pollen 296:301 In the present study, the effects of two important oxidizing atmospheric pollutants (O3 and NO2) on the allergenic properties and chemical composition of Platanus x acerifolia pollen were studied. 28477486 4 20 theme allergenicity 693:705 arg1 changes 707:713 pollen allergenicity changes 686:713 pollen allergenicity changes 686:713 Immunochemical analysis showed that pollen allergenicity changes were different according to the pollutant tested (gas or mixture of gasses) and that the same pollutant gas may interact in a different manner with each specific allergen. 28477486 2 21 theme concentration 412:424 arg1 levels 426:431 atmospheric concentration levels 400:431 atmospheric concentration levels (O3: 0.061ppm; NO2: 0.025ppm and the mixture of O3 and NO2: 0.060 and 0.031ppm respectively) 400:524 Pollen samples were subjected to O3 and/or NO2 under in vitro conditions for 6h at atmospheric concentration levels (O3: 0.061ppm; NO2: 0.025ppm and the mixture of O3 and NO2: 0.060 and 0.031ppm respectively). 28477486 6 22 theme components 1231:1240 arg1 modifications 1210:1222 further modifications 1202:1222 further modifications of its components induced by air pollution, which can compromise the pollen function 1202:1307 This indicates that while airborne, the pollen wall suffers further modifications of its components induced by air pollution, which can compromise the pollen function. 28477486 6 23 theme air 1253:1255 arg1 pollution 1257:1265 air pollution 1253:1265 air pollution 1253:1265 This indicates that while airborne, the pollen wall suffers further modifications of its components induced by air pollution, which can compromise the pollen function. 28477486 4 24 theme Immunochemical 650:663 arg1 analysis 665:672 Immunochemical analysis 650:672 Immunochemical analysis 650:672 Immunochemical analysis showed that pollen allergenicity changes were different according to the pollutant tested (gas or mixture of gasses) and that the same pollutant gas may interact in a different manner with each specific allergen. 28477486 2 25 theme atmospheric 400:410 arg1 levels 426:431 atmospheric concentration levels 400:431 atmospheric concentration levels (O3: 0.061ppm; NO2: 0.025ppm and the mixture of O3 and NO2: 0.060 and 0.031ppm respectively) 400:524 Pollen samples were subjected to O3 and/or NO2 under in vitro conditions for 6h at atmospheric concentration levels (O3: 0.061ppm; NO2: 0.025ppm and the mixture of O3 and NO2: 0.060 and 0.031ppm respectively). 28477486 3 26 theme Pla 549:551 arg1 a 553:553 Pla a 1 549:555 Pla a 1 549:555 Immunoblotting (using Pla a 1 and Pla a 2 antibodies), infrared and X-ray photoelectron spectroscopy techniques were used. 28477486 1 27 theme important 161:169 arg1 NO2 212:214 NO2 212:214 NO2 212:214 In the present study, the effects of two important oxidizing atmospheric pollutants (O3 and NO2) on the allergenic properties and chemical composition of Platanus x acerifolia pollen were studied. 28477486 1 27 theme important 161:169 arg1 O3 205:206 O3 205:206 O3 205:206 In the present study, the effects of two important oxidizing atmospheric pollutants (O3 and NO2) on the allergenic properties and chemical composition of Platanus x acerifolia pollen were studied. 28477486 1 27 theme important 161:169 arg1 pollutants 193:202 two important oxidizing atmospheric pollutants 157:202 two important oxidizing atmospheric pollutants (O3 and NO2) 157:215 In the present study, the effects of two important oxidizing atmospheric pollutants (O3 and NO2) on the allergenic properties and chemical composition of Platanus x acerifolia pollen were studied. 28477486 1 28 theme chemical 250:257 arg1 composition 259:269 chemical composition 250:269 chemical composition 250:269 In the present study, the effects of two important oxidizing atmospheric pollutants (O3 and NO2) on the allergenic properties and chemical composition of Platanus x acerifolia pollen were studied. 28477486 2 29 theme NO2 488:490 arg1 0.025ppm 453:460 0.025ppm 453:460 0.025ppm 453:460 Pollen samples were subjected to O3 and/or NO2 under in vitro conditions for 6h at atmospheric concentration levels (O3: 0.061ppm; NO2: 0.025ppm and the mixture of O3 and NO2: 0.060 and 0.031ppm respectively). 28477486 2 29 theme NO2 488:490 arg1 mixture 470:476 the mixture 466:476 the mixture of O3 and NO2 466:490 Pollen samples were subjected to O3 and/or NO2 under in vitro conditions for 6h at atmospheric concentration levels (O3: 0.061ppm; NO2: 0.025ppm and the mixture of O3 and NO2: 0.060 and 0.031ppm respectively). 28477486 4 30 theme gasses 783:788 arg1 mixture 772:778 gas or mixture 765:778 mixture 772:778 Immunochemical analysis showed that pollen allergenicity changes were different according to the pollutant tested (gas or mixture of gasses) and that the same pollutant gas may interact in a different manner with each specific allergen. 28477486 4 30 theme gasses 783:788 arg1 gas 765:767 gas or mixture 765:778 gas 765:767 Immunochemical analysis showed that pollen allergenicity changes were different according to the pollutant tested (gas or mixture of gasses) and that the same pollutant gas may interact in a different manner with each specific allergen. 28477486 1 31 theme oxidizing 171:179 arg1 NO2 212:214 NO2 212:214 NO2 212:214 In the present study, the effects of two important oxidizing atmospheric pollutants (O3 and NO2) on the allergenic properties and chemical composition of Platanus x acerifolia pollen were studied. 28477486 1 31 theme oxidizing 171:179 arg1 O3 205:206 O3 205:206 O3 205:206 In the present study, the effects of two important oxidizing atmospheric pollutants (O3 and NO2) on the allergenic properties and chemical composition of Platanus x acerifolia pollen were studied. 28477486 1 31 theme oxidizing 171:179 arg1 pollutants 193:202 two important oxidizing atmospheric pollutants 157:202 two important oxidizing atmospheric pollutants (O3 and NO2) 157:215 In the present study, the effects of two important oxidizing atmospheric pollutants (O3 and NO2) on the allergenic properties and chemical composition of Platanus x acerifolia pollen were studied. 28477486 0 32 theme O3 10:11 arg1 pollutants 33:42 O3 and NO2 atmospheric pollutants 10:42 O3 and NO2 atmospheric pollutants 10:42 Effect of O3 and NO2 atmospheric pollutants on Platanus x acerifolia pollen: Immunochemical and spectroscopic analysis. 28477486 5 33 theme pollen 1029:1034 arg1 polysaccharides 1006:1020 polysaccharides 1006:1020 polysaccharides 1006:1020 The spectroscopy results showed modifications in the FTIR spectral features of bands assigned to proteins, lipids, and polysaccharides of the pollen exposed to the pollutants, as well as in the XPS spectra high-resolution components C 1s, N 1s, and O 1s. 28477486 5 33 theme pollen 1029:1034 arg1 proteins 984:991 proteins 984:991 proteins 984:991 The spectroscopy results showed modifications in the FTIR spectral features of bands assigned to proteins, lipids, and polysaccharides of the pollen exposed to the pollutants, as well as in the XPS spectra high-resolution components C 1s, N 1s, and O 1s. 28477486 5 33 theme pollen 1029:1034 arg1 lipids 994:999 lipids 994:999 lipids 994:999 The spectroscopy results showed modifications in the FTIR spectral features of bands assigned to proteins, lipids, and polysaccharides of the pollen exposed to the pollutants, as well as in the XPS spectra high-resolution components C 1s, N 1s, and O 1s. 28477486 3 34 used used 644:647 arg2 infrared 582:589 infrared 582:589 infrared 582:589 Immunoblotting (using Pla a 1 and Pla a 2 antibodies), infrared and X-ray photoelectron spectroscopy techniques were used. 28477486 3 34 used used 644:647 arg2 Immunoblotting 527:540 Immunoblotting 527:540 Immunoblotting 527:540 Immunoblotting (using Pla a 1 and Pla a 2 antibodies), infrared and X-ray photoelectron spectroscopy techniques were used. 28477486 3 34 used used 644:647 arg2 spectroscopy 615:626 X-ray photoelectron spectroscopy 595:626 X-ray photoelectron spectroscopy 595:626 Immunoblotting (using Pla a 1 and Pla a 2 antibodies), infrared and X-ray photoelectron spectroscopy techniques were used. 28477486 1 35 theme atmospheric 181:191 arg1 NO2 212:214 NO2 212:214 NO2 212:214 In the present study, the effects of two important oxidizing atmospheric pollutants (O3 and NO2) on the allergenic properties and chemical composition of Platanus x acerifolia pollen were studied. 28477486 1 35 theme atmospheric 181:191 arg1 O3 205:206 O3 205:206 O3 205:206 In the present study, the effects of two important oxidizing atmospheric pollutants (O3 and NO2) on the allergenic properties and chemical composition of Platanus x acerifolia pollen were studied. 28477486 1 35 theme atmospheric 181:191 arg1 pollutants 193:202 two important oxidizing atmospheric pollutants 157:202 two important oxidizing atmospheric pollutants (O3 and NO2) 157:215 In the present study, the effects of two important oxidizing atmospheric pollutants (O3 and NO2) on the allergenic properties and chemical composition of Platanus x acerifolia pollen were studied. 28477486 0 36 theme atmospheric 21:31 arg1 pollutants 33:42 O3 and NO2 atmospheric pollutants 10:42 O3 and NO2 atmospheric pollutants 10:42 Effect of O3 and NO2 atmospheric pollutants on Platanus x acerifolia pollen: Immunochemical and spectroscopic analysis. 28477486 2 37 theme O3 481:482 arg1 0.025ppm 453:460 0.025ppm 453:460 0.025ppm 453:460 Pollen samples were subjected to O3 and/or NO2 under in vitro conditions for 6h at atmospheric concentration levels (O3: 0.061ppm; NO2: 0.025ppm and the mixture of O3 and NO2: 0.060 and 0.031ppm respectively). 28477486 2 37 theme O3 481:482 arg1 mixture 470:476 the mixture 466:476 the mixture of O3 and NO2 466:490 Pollen samples were subjected to O3 and/or NO2 under in vitro conditions for 6h at atmospheric concentration levels (O3: 0.061ppm; NO2: 0.025ppm and the mixture of O3 and NO2: 0.060 and 0.031ppm respectively). 28477486 3 38 theme a 565:565 arg1 antibodies 569:578 Pla a 1 and Pla a 2 antibodies 549:578 Pla a 1 and Pla a 2 antibodies 549:578 Immunoblotting (using Pla a 1 and Pla a 2 antibodies), infrared and X-ray photoelectron spectroscopy techniques were used. 28477486 3 39 dep Immunoblotting 527:540 arg1 techniques 628:637 techniques 628:637 techniques 628:637 Immunoblotting (using Pla a 1 and Pla a 2 antibodies), infrared and X-ray photoelectron spectroscopy techniques were used. 28477486 1 40 theme pollutants 193:202 arg1 effects 146:152 the effects 142:152 the effects of two important oxidizing atmospheric pollutants (O3 and NO2) on the allergenic properties and chemical composition of Platanus x acerifolia pollen 142:301 In the present study, the effects of two important oxidizing atmospheric pollutants (O3 and NO2) on the allergenic properties and chemical composition of Platanus x acerifolia pollen were studied. 28477486 0 41 theme NO2 17:19 arg1 pollutants 33:42 O3 and NO2 atmospheric pollutants 10:42 O3 and NO2 atmospheric pollutants 10:42 Effect of O3 and NO2 atmospheric pollutants on Platanus x acerifolia pollen: Immunochemical and spectroscopic analysis. 28477486 1 42 theme Platanus 274:281 arg1 composition 259:269 chemical composition 250:269 chemical composition 250:269 In the present study, the effects of two important oxidizing atmospheric pollutants (O3 and NO2) on the allergenic properties and chemical composition of Platanus x acerifolia pollen were studied. 28477486 1 42 theme Platanus 274:281 arg1 properties 235:244 allergenic properties 224:244 allergenic properties 224:244 In the present study, the effects of two important oxidizing atmospheric pollutants (O3 and NO2) on the allergenic properties and chemical composition of Platanus x acerifolia pollen were studied. 28477486 6 43 theme pollen 1182:1187 arg1 wall 1189:1192 the pollen wall 1178:1192 the pollen wall 1178:1192 This indicates that while airborne, the pollen wall suffers further modifications of its components induced by air pollution, which can compromise the pollen function. 28477486 2 44 dep in 370:371 arg1 vitro 373:377 vitro 373:377 vitro 373:377 Pollen samples were subjected to O3 and/or NO2 under in vitro conditions for 6h at atmospheric concentration levels (O3: 0.061ppm; NO2: 0.025ppm and the mixture of O3 and NO2: 0.060 and 0.031ppm respectively). 28477486 2 45 theme in 370:371 arg1 conditions 379:388 in vitro conditions 370:388 in vitro conditions for 6h at atmospheric concentration levels (O3: 0.061ppm; NO2: 0.025ppm and the mixture of O3 and NO2: 0.060 and 0.031ppm respectively) 370:524 Pollen samples were subjected to O3 and/or NO2 under in vitro conditions for 6h at atmospheric concentration levels (O3: 0.061ppm; NO2: 0.025ppm and the mixture of O3 and NO2: 0.060 and 0.031ppm respectively). 28477486 4 46 theme same 804:807 arg1 gas 819:821 the same pollutant gas 800:821 the same pollutant gas 800:821 Immunochemical analysis showed that pollen allergenicity changes were different according to the pollutant tested (gas or mixture of gasses) and that the same pollutant gas may interact in a different manner with each specific allergen. 28477486 4 47 theme specific 868:875 arg1 allergen 877:884 each specific allergen 863:884 each specific allergen 863:884 Immunochemical analysis showed that pollen allergenicity changes were different according to the pollutant tested (gas or mixture of gasses) and that the same pollutant gas may interact in a different manner with each specific allergen. 28477486 5 48 theme FTIR 940:943 arg1 features 954:961 the FTIR spectral features 936:961 the FTIR spectral features of bands assigned to proteins, lipids, and polysaccharides of the pollen exposed to the pollutants 936:1060 The spectroscopy results showed modifications in the FTIR spectral features of bands assigned to proteins, lipids, and polysaccharides of the pollen exposed to the pollutants, as well as in the XPS spectra high-resolution components C 1s, N 1s, and O 1s. 28477486 6 49 theme pollen 1293:1298 arg1 function 1300:1307 the pollen function 1289:1307 the pollen function 1289:1307 This indicates that while airborne, the pollen wall suffers further modifications of its components induced by air pollution, which can compromise the pollen function. 28477486 2 50 theme Pollen 317:322 arg1 samples 324:330 Pollen samples 317:330 Pollen samples 317:330 Pollen samples were subjected to O3 and/or NO2 under in vitro conditions for 6h at atmospheric concentration levels (O3: 0.061ppm; NO2: 0.025ppm and the mixture of O3 and NO2: 0.060 and 0.031ppm respectively). 28477486 0 51 theme pollutants 33:42 arg1 Effect 0:5 Effect 0:5 Effect of O3 and NO2 atmospheric pollutants on Platanus x acerifolia pollen: Immunochemical and spectroscopic analysis. 0:118 Effect of O3 and NO2 atmospheric pollutants on Platanus x acerifolia pollen: Immunochemical and spectroscopic analysis. 28477486 1 52 theme acerifolia 285:294 arg1 composition 259:269 chemical composition 250:269 chemical composition 250:269 In the present study, the effects of two important oxidizing atmospheric pollutants (O3 and NO2) on the allergenic properties and chemical composition of Platanus x acerifolia pollen were studied. 28477486 1 52 theme acerifolia 285:294 arg1 properties 235:244 allergenic properties 224:244 allergenic properties 224:244 In the present study, the effects of two important oxidizing atmospheric pollutants (O3 and NO2) on the allergenic properties and chemical composition of Platanus x acerifolia pollen were studied. 28477486 5 53 theme spectral 945:952 arg1 features 954:961 the FTIR spectral features 936:961 the FTIR spectral features of bands assigned to proteins, lipids, and polysaccharides of the pollen exposed to the pollutants 936:1060 The spectroscopy results showed modifications in the FTIR spectral features of bands assigned to proteins, lipids, and polysaccharides of the pollen exposed to the pollutants, as well as in the XPS spectra high-resolution components C 1s, N 1s, and O 1s. 28477486 1 54 dep properties 235:244 arg1 the 220:222 the 220:222 the 220:222 In the present study, the effects of two important oxidizing atmospheric pollutants (O3 and NO2) on the allergenic properties and chemical composition of Platanus x acerifolia pollen were studied. 28477486 1 55 dep pollutants 193:202 arg1 NO2 212:214 NO2 212:214 NO2 212:214 In the present study, the effects of two important oxidizing atmospheric pollutants (O3 and NO2) on the allergenic properties and chemical composition of Platanus x acerifolia pollen were studied. 28477486 1 55 dep pollutants 193:202 arg1 O3 205:206 O3 205:206 O3 205:206 In the present study, the effects of two important oxidizing atmospheric pollutants (O3 and NO2) on the allergenic properties and chemical composition of Platanus x acerifolia pollen were studied. 28477486 1 55 dep pollutants 193:202 arg1 pollutants 193:202 two important oxidizing atmospheric pollutants 157:202 two important oxidizing atmospheric pollutants (O3 and NO2) 157:215 In the present study, the effects of two important oxidizing atmospheric pollutants (O3 and NO2) on the allergenic properties and chemical composition of Platanus x acerifolia pollen were studied. 28477486 5 56 theme C 1120:1120 arg1 1s 1122:1123 high-resolution components C 1s 1093:1123 high-resolution components C 1s 1093:1123 The spectroscopy results showed modifications in the FTIR spectral features of bands assigned to proteins, lipids, and polysaccharides of the pollen exposed to the pollutants, as well as in the XPS spectra high-resolution components C 1s, N 1s, and O 1s. 28477486 5 56 theme C 1120:1120 arg1 spectra 1085:1091 the XPS spectra high-resolution components C 1s, N 1s, and O 1s 1077:1139 the XPS spectra high-resolution components C 1s, N 1s, and O 1s 1077:1139 The spectroscopy results showed modifications in the FTIR spectral features of bands assigned to proteins, lipids, and polysaccharides of the pollen exposed to the pollutants, as well as in the XPS spectra high-resolution components C 1s, N 1s, and O 1s. 28477486 4 57 theme pollutant 809:817 arg1 gas 819:821 the same pollutant gas 800:821 the same pollutant gas 800:821 Immunochemical analysis showed that pollen allergenicity changes were different according to the pollutant tested (gas or mixture of gasses) and that the same pollutant gas may interact in a different manner with each specific allergen. 28477486 5 58 theme bands 966:970 arg1 features 954:961 the FTIR spectral features 936:961 the FTIR spectral features of bands assigned to proteins, lipids, and polysaccharides of the pollen exposed to the pollutants 936:1060 The spectroscopy results showed modifications in the FTIR spectral features of bands assigned to proteins, lipids, and polysaccharides of the pollen exposed to the pollutants, as well as in the XPS spectra high-resolution components C 1s, N 1s, and O 1s. 28477486 3 59 theme a 553:553 arg1 antibodies 569:578 Pla a 1 and Pla a 2 antibodies 549:578 Pla a 1 and Pla a 2 antibodies 549:578 Immunoblotting (using Pla a 1 and Pla a 2 antibodies), infrared and X-ray photoelectron spectroscopy techniques were used. 28477486 0 60 theme x 56:56 arg1 pollen 69:74 Platanus x acerifolia pollen 47:74 Platanus x acerifolia pollen 47:74 Effect of O3 and NO2 atmospheric pollutants on Platanus x acerifolia pollen: Immunochemical and spectroscopic analysis. 28477486 5 61 dep spectra 1085:1091 arg1 1s 1122:1123 high-resolution components C 1s 1093:1123 high-resolution components C 1s 1093:1123 The spectroscopy results showed modifications in the FTIR spectral features of bands assigned to proteins, lipids, and polysaccharides of the pollen exposed to the pollutants, as well as in the XPS spectra high-resolution components C 1s, N 1s, and O 1s. 28477486 5 61 dep spectra 1085:1091 arg1 1s 1128:1129 N 1s 1126:1129 N 1s 1126:1129 The spectroscopy results showed modifications in the FTIR spectral features of bands assigned to proteins, lipids, and polysaccharides of the pollen exposed to the pollutants, as well as in the XPS spectra high-resolution components C 1s, N 1s, and O 1s. 28477486 5 61 dep spectra 1085:1091 arg1 spectra 1085:1091 the XPS spectra high-resolution components C 1s, N 1s, and O 1s 1077:1139 the XPS spectra high-resolution components C 1s, N 1s, and O 1s 1077:1139 The spectroscopy results showed modifications in the FTIR spectral features of bands assigned to proteins, lipids, and polysaccharides of the pollen exposed to the pollutants, as well as in the XPS spectra high-resolution components C 1s, N 1s, and O 1s. 28477486 5 61 dep spectra 1085:1091 arg1 1s 1138:1139 O 1s 1136:1139 O 1s 1136:1139 The spectroscopy results showed modifications in the FTIR spectral features of bands assigned to proteins, lipids, and polysaccharides of the pollen exposed to the pollutants, as well as in the XPS spectra high-resolution components C 1s, N 1s, and O 1s. 28477486 1 62 theme present 127:133 arg1 study 135:139 the present study 123:139 the present study 123:139 In the present study, the effects of two important oxidizing atmospheric pollutants (O3 and NO2) on the allergenic properties and chemical composition of Platanus x acerifolia pollen were studied. 28477486 0 63 theme Platanus 47:54 arg1 pollen 69:74 Platanus x acerifolia pollen 47:74 Platanus x acerifolia pollen 47:74 Effect of O3 and NO2 atmospheric pollutants on Platanus x acerifolia pollen: Immunochemical and spectroscopic analysis. 28477486 3 64 theme X-ray 595:599 arg1 spectroscopy 615:626 X-ray photoelectron spectroscopy 595:626 X-ray photoelectron spectroscopy 595:626 Immunoblotting (using Pla a 1 and Pla a 2 antibodies), infrared and X-ray photoelectron spectroscopy techniques were used. 28477486 0 65 dep Effect 0:5 arg1 Immunochemical 77:90 Immunochemical 77:90 Immunochemical 77:90 Effect of O3 and NO2 atmospheric pollutants on Platanus x acerifolia pollen: Immunochemical and spectroscopic analysis. 28477486 0 65 dep Effect 0:5 arg1 analysis 110:117 spectroscopic analysis 96:117 spectroscopic analysis 96:117 Effect of O3 and NO2 atmospheric pollutants on Platanus x acerifolia pollen: Immunochemical and spectroscopic analysis. 28477486 1 66 from effects 146:152 arg1 composition 259:269 chemical composition 250:269 chemical composition 250:269 In the present study, the effects of two important oxidizing atmospheric pollutants (O3 and NO2) on the allergenic properties and chemical composition of Platanus x acerifolia pollen were studied. 28477486 1 66 from effects 146:152 arg1 properties 235:244 allergenic properties 224:244 allergenic properties 224:244 In the present study, the effects of two important oxidizing atmospheric pollutants (O3 and NO2) on the allergenic properties and chemical composition of Platanus x acerifolia pollen were studied. 28477486 5 67 theme N 1126:1126 arg1 1s 1128:1129 N 1s 1126:1129 N 1s 1126:1129 The spectroscopy results showed modifications in the FTIR spectral features of bands assigned to proteins, lipids, and polysaccharides of the pollen exposed to the pollutants, as well as in the XPS spectra high-resolution components C 1s, N 1s, and O 1s. 28477486 5 67 theme N 1126:1126 arg1 spectra 1085:1091 the XPS spectra high-resolution components C 1s, N 1s, and O 1s 1077:1139 the XPS spectra high-resolution components C 1s, N 1s, and O 1s 1077:1139 The spectroscopy results showed modifications in the FTIR spectral features of bands assigned to proteins, lipids, and polysaccharides of the pollen exposed to the pollutants, as well as in the XPS spectra high-resolution components C 1s, N 1s, and O 1s. 27291648 8 0 theme low 1160:1162 arg1 level 1164:1168 low level 1160:1168 low level 1160:1168 One such structural isomer at low level, terminal GlcNAc of G1F+GlcNAc, was identified to be linked at the 1,6 branch. 27291648 11 1 theme different 1622:1630 arg1 lots 1632:1635 different lots 1622:1635 different lots 1622:1635 Using this approach, different lots or different CHO produced mAbs was thoroughly examined and found that the newly identified "Man8" (Man7+Glc) was also present in different batches and in some commercially available therapeutic mAbs. 27291648 6 2 theme sialic 877:882 arg1 acid 884:887 terminal sialic acid 868:887 terminal sialic acid attached in the 1,6 branch at 2,3 position 868:930 The developed method successfully characterized structural isomers of A1G1F (assigned as terminal sialic acid attached in the 1,6 branch at 2,3 position), and A1G1F' (assigned as terminal sialic acid attached in the 1,3 branch at 2,3 position). 27291648 6 3 from position 923:930 arg1 branch 909:914 the 1,6 branch 901:914 the 1,6 branch at 2,3 position 901:930 The developed method successfully characterized structural isomers of A1G1F (assigned as terminal sialic acid attached in the 1,6 branch at 2,3 position), and A1G1F' (assigned as terminal sialic acid attached in the 1,3 branch at 2,3 position). 27291648 11 4 from present 1755:1761 arg1 mAbs 1831:1834 some commercially available therapeutic mAbs 1791:1834 some commercially available therapeutic mAbs 1791:1834 Using this approach, different lots or different CHO produced mAbs was thoroughly examined and found that the newly identified "Man8" (Man7+Glc) was also present in different batches and in some commercially available therapeutic mAbs. 27291648 11 4 from present 1755:1761 arg1 batches 1776:1782 different batches 1766:1782 different batches 1766:1782 Using this approach, different lots or different CHO produced mAbs was thoroughly examined and found that the newly identified "Man8" (Man7+Glc) was also present in different batches and in some commercially available therapeutic mAbs. 27291648 4 5 theme signature 688:696 arg1 ions 700:703 the signature D ions 684:703 the signature D ions 684:703 The glycan structure was characterized by MS(n) fragmentation in negative ion mode followed by identification of the signature D ions. 27291648 2 6 theme monoclonal 288:297 arg1 antibody 299:306 a recombinant monoclonal antibody 274:306 a recombinant monoclonal antibody 274:306 N-linked glycans of a recombinant monoclonal antibody were released by PNGase F and labeled with 2-aminobenzamide (2-AB) fluorescent tag. 27291648 1 7 theme isomers 184:190 arg1 characterization 140:155 online characterization 133:155 online characterization of low abundant structural isomers of N-linked glycans in biological therapeutics 133:237 An effective LC-MS based method for online characterization of low abundant structural isomers of N-linked glycans in biological therapeutics was developed. 27291648 8 8 theme G1F+GlcNAc 1190:1199 arg1 One 1130:1132 One 1130:1132 One 1130:1132 One such structural isomer at low level, terminal GlcNAc of G1F+GlcNAc, was identified to be linked at the 1,6 branch. 27291648 8 8 theme G1F+GlcNAc 1190:1199 arg1 GlcNAc 1180:1185 terminal GlcNAc 1171:1185 terminal GlcNAc of G1F+GlcNAc 1171:1199 One such structural isomer at low level, terminal GlcNAc of G1F+GlcNAc, was identified to be linked at the 1,6 branch. 27291648 6 9 dep A1G1F 849:853 arg1 assigned 856:863 assigned 856:863 assigned as terminal sialic acid attached in the 1,6 branch at 2,3 position 856:930 The developed method successfully characterized structural isomers of A1G1F (assigned as terminal sialic acid attached in the 1,6 branch at 2,3 position), and A1G1F' (assigned as terminal sialic acid attached in the 1,3 branch at 2,3 position). 27291648 6 9 dep A1G1F 849:853 arg1 assigned 946:953 assigned 946:953 assigned as terminal sialic acid attached in the 1,3 branch at 2,3 position 946:1020 The developed method successfully characterized structural isomers of A1G1F (assigned as terminal sialic acid attached in the 1,6 branch at 2,3 position), and A1G1F' (assigned as terminal sialic acid attached in the 1,3 branch at 2,3 position). 27291648 4 10 theme ions 700:703 arg1 identification 666:679 identification 666:679 identification of the signature D ions 666:703 The glycan structure was characterized by MS(n) fragmentation in negative ion mode followed by identification of the signature D ions. 27291648 11 11 theme different 1766:1774 arg1 batches 1776:1782 different batches 1766:1782 different batches 1766:1782 Using this approach, different lots or different CHO produced mAbs was thoroughly examined and found that the newly identified "Man8" (Man7+Glc) was also present in different batches and in some commercially available therapeutic mAbs. 27291648 9 12 contain containing 1386:1395 arg2 mannoses 1403:1410 three mannoses 1397:1410 three mannoses 1397:1410 Additionally, another low level structural isomer, previously assigned as Man8 glycan, was found to be Man7+Glc glycan as its 1,3 branch containing three mannoses and one terminal glucose. 27291648 9 12 contain containing 1386:1395 arg1 branch 1379:1384 its 1,3 branch 1371:1384 its 1,3 branch containing three mannoses 1371:1410 Additionally, another low level structural isomer, previously assigned as Man8 glycan, was found to be Man7+Glc glycan as its 1,3 branch containing three mannoses and one terminal glucose. 27291648 1 13 theme N-linked 195:202 arg1 glycans 204:210 N-linked glycans 195:210 N-linked glycans in biological therapeutics 195:237 An effective LC-MS based method for online characterization of low abundant structural isomers of N-linked glycans in biological therapeutics was developed. 27291648 5 14 theme linkage 758:764 arg1 information 766:776 linkage information 758:776 linkage information 758:776 The assignment included monosaccharide sequence and linkage information. 27291648 6 15 theme sialic 967:972 arg1 acid 974:977 terminal sialic acid 958:977 terminal sialic acid attached in the 1,3 branch at 2,3 position 958:1020 The developed method successfully characterized structural isomers of A1G1F (assigned as terminal sialic acid attached in the 1,6 branch at 2,3 position), and A1G1F' (assigned as terminal sialic acid attached in the 1,3 branch at 2,3 position). 27291648 1 16 from glycans 204:210 arg1 therapeutics 226:237 biological therapeutics 215:237 biological therapeutics 215:237 An effective LC-MS based method for online characterization of low abundant structural isomers of N-linked glycans in biological therapeutics was developed. 27291648 1 17 theme online 133:138 arg1 characterization 140:155 online characterization 133:155 online characterization of low abundant structural isomers of N-linked glycans in biological therapeutics 133:237 An effective LC-MS based method for online characterization of low abundant structural isomers of N-linked glycans in biological therapeutics was developed. 27291648 2 18 link N-linked 254:261 arg1 glycans 263:269 N-linked glycans 254:269 N-linked glycans of a recombinant monoclonal antibody 254:306 N-linked glycans of a recombinant monoclonal antibody were released by PNGase F and labeled with 2-aminobenzamide (2-AB) fluorescent tag. 27291648 0 19 theme Biological 63:72 arg1 Therapeutics 74:85 Biological Therapeutics 63:85 Biological Therapeutics 63:85 Identification of Low Abundant Isomeric N-Glycan Structures in Biological Therapeutics by LC/MS. 27291648 9 20 theme low 1271:1273 arg1 isomer 1292:1297 another low level structural isomer 1263:1297 another low level structural isomer 1263:1297 Additionally, another low level structural isomer, previously assigned as Man8 glycan, was found to be Man7+Glc glycan as its 1,3 branch containing three mannoses and one terminal glucose. 27291648 10 21 theme terminal 1563:1570 arg1 Man+glucose 1587:1597 Man+glucose 1587:1597 Man+glucose 1587:1597 The identification was further confirmed by a purified α-1,2-endomannosidase enzyme to generate the cleavage of α-1,3 linked terminal disaccharides (Man+glucose). 27291648 10 21 theme terminal 1563:1570 arg1 disaccharides 1572:1584 α-1,3 linked terminal disaccharides 1550:1584 α-1,3 linked terminal disaccharides (Man+glucose) 1550:1598 The identification was further confirmed by a purified α-1,2-endomannosidase enzyme to generate the cleavage of α-1,3 linked terminal disaccharides (Man+glucose). 27291648 9 22 theme structural 1281:1290 arg1 isomer 1292:1297 another low level structural isomer 1263:1297 another low level structural isomer 1263:1297 Additionally, another low level structural isomer, previously assigned as Man8 glycan, was found to be Man7+Glc glycan as its 1,3 branch containing three mannoses and one terminal glucose. 27291648 1 23 theme abundant 164:171 arg1 isomers 184:190 low abundant structural isomers 160:190 low abundant structural isomers of N-linked glycans in biological therapeutics 160:237 An effective LC-MS based method for online characterization of low abundant structural isomers of N-linked glycans in biological therapeutics was developed. 27291648 6 24 theme 2,3 1009:1011 arg1 position 1013:1020 2,3 position 1009:1020 2,3 position 1009:1020 The developed method successfully characterized structural isomers of A1G1F (assigned as terminal sialic acid attached in the 1,6 branch at 2,3 position), and A1G1F' (assigned as terminal sialic acid attached in the 1,3 branch at 2,3 position). 27291648 0 25 from Identification 0:13 arg1 Therapeutics 74:85 Biological Therapeutics 63:85 Biological Therapeutics 63:85 Identification of Low Abundant Isomeric N-Glycan Structures in Biological Therapeutics by LC/MS. 27291648 0 26 from Structures 49:58 arg1 Therapeutics 74:85 Biological Therapeutics 63:85 Biological Therapeutics 63:85 Identification of Low Abundant Isomeric N-Glycan Structures in Biological Therapeutics by LC/MS. 27291648 3 27 theme chromatography-hydrophilic 460:485 arg1 chromatography 506:519 online ultraperformance liquid chromatography-hydrophilic interaction liquid chromatography 429:519 online ultraperformance liquid chromatography-hydrophilic interaction liquid chromatography (UPLC-HILIC) coupled with mass spectrometry (MS) 429:568 The labeled glycans were analyzed by online ultraperformance liquid chromatography-hydrophilic interaction liquid chromatography (UPLC-HILIC) coupled with mass spectrometry (MS). 27291648 3 27 theme chromatography-hydrophilic 460:485 arg1 UPLC-HILIC 522:531 UPLC-HILIC 522:531 UPLC-HILIC 522:531 The labeled glycans were analyzed by online ultraperformance liquid chromatography-hydrophilic interaction liquid chromatography (UPLC-HILIC) coupled with mass spectrometry (MS). 27291648 3 28 theme labeled 396:402 arg1 glycans 404:410 The labeled glycans 392:410 The labeled glycans 392:410 The labeled glycans were analyzed by online ultraperformance liquid chromatography-hydrophilic interaction liquid chromatography (UPLC-HILIC) coupled with mass spectrometry (MS). 27291648 6 29 from position 1013:1020 arg1 branch 999:1004 the 1,3 branch 991:1004 the 1,3 branch at 2,3 position 991:1020 The developed method successfully characterized structural isomers of A1G1F (assigned as terminal sialic acid attached in the 1,6 branch at 2,3 position), and A1G1F' (assigned as terminal sialic acid attached in the 1,3 branch at 2,3 position). 27291648 3 30 theme ultraperformance 436:451 arg1 chromatography 506:519 online ultraperformance liquid chromatography-hydrophilic interaction liquid chromatography 429:519 online ultraperformance liquid chromatography-hydrophilic interaction liquid chromatography (UPLC-HILIC) coupled with mass spectrometry (MS) 429:568 The labeled glycans were analyzed by online ultraperformance liquid chromatography-hydrophilic interaction liquid chromatography (UPLC-HILIC) coupled with mass spectrometry (MS). 27291648 3 30 theme ultraperformance 436:451 arg1 UPLC-HILIC 522:531 UPLC-HILIC 522:531 UPLC-HILIC 522:531 The labeled glycans were analyzed by online ultraperformance liquid chromatography-hydrophilic interaction liquid chromatography (UPLC-HILIC) coupled with mass spectrometry (MS). 27291648 9 31 theme Man8 1323:1326 arg1 glycan 1328:1333 Man8 glycan 1323:1333 Man8 glycan 1323:1333 Additionally, another low level structural isomer, previously assigned as Man8 glycan, was found to be Man7+Glc glycan as its 1,3 branch containing three mannoses and one terminal glucose. 27291648 0 32 theme Low 18:20 arg1 Structures 49:58 Low Abundant Isomeric N-Glycan Structures 18:58 Low Abundant Isomeric N-Glycan Structures in Biological Therapeutics 18:85 Identification of Low Abundant Isomeric N-Glycan Structures in Biological Therapeutics by LC/MS. 27291648 6 33 theme 2,3 919:921 arg1 position 923:930 2,3 position 919:930 2,3 position 919:930 The developed method successfully characterized structural isomers of A1G1F (assigned as terminal sialic acid attached in the 1,6 branch at 2,3 position), and A1G1F' (assigned as terminal sialic acid attached in the 1,3 branch at 2,3 position). 27291648 1 34 theme LC-MS 110:114 arg1 method 122:127 An effective LC-MS based method 97:127 An effective LC-MS based method for online characterization of low abundant structural isomers of N-linked glycans in biological therapeutics 97:237 An effective LC-MS based method for online characterization of low abundant structural isomers of N-linked glycans in biological therapeutics was developed. 27291648 3 35 theme liquid 499:504 arg1 chromatography 506:519 online ultraperformance liquid chromatography-hydrophilic interaction liquid chromatography 429:519 online ultraperformance liquid chromatography-hydrophilic interaction liquid chromatography (UPLC-HILIC) coupled with mass spectrometry (MS) 429:568 The labeled glycans were analyzed by online ultraperformance liquid chromatography-hydrophilic interaction liquid chromatography (UPLC-HILIC) coupled with mass spectrometry (MS). 27291648 3 35 theme liquid 499:504 arg1 UPLC-HILIC 522:531 UPLC-HILIC 522:531 UPLC-HILIC 522:531 The labeled glycans were analyzed by online ultraperformance liquid chromatography-hydrophilic interaction liquid chromatography (UPLC-HILIC) coupled with mass spectrometry (MS). 27291648 0 36 theme Isomeric 31:38 arg1 Structures 49:58 Low Abundant Isomeric N-Glycan Structures 18:58 Low Abundant Isomeric N-Glycan Structures in Biological Therapeutics 18:85 Identification of Low Abundant Isomeric N-Glycan Structures in Biological Therapeutics by LC/MS. 27291648 0 37 theme Structures 49:58 arg1 Identification 0:13 Identification 0:13 Identification of Low Abundant Isomeric N-Glycan Structures in Biological Therapeutics by LC/MS. 0:95 Identification of Low Abundant Isomeric N-Glycan Structures in Biological Therapeutics by LC/MS. 27291648 4 38 theme glycan 575:580 arg1 structure 582:590 The glycan structure 571:590 The glycan structure 571:590 The glycan structure was characterized by MS(n) fragmentation in negative ion mode followed by identification of the signature D ions. 27291648 10 39 theme α-1,2-endomannosidase 1493:1513 arg1 enzyme 1515:1520 a purified α-1,2-endomannosidase enzyme 1482:1520 a purified α-1,2-endomannosidase enzyme to generate the cleavage of α-1,3 linked terminal disaccharides (Man+glucose) 1482:1598 The identification was further confirmed by a purified α-1,2-endomannosidase enzyme to generate the cleavage of α-1,3 linked terminal disaccharides (Man+glucose). 27291648 11 40 theme identified 1717:1726 arg1 " 1733:1733 the newly identified "Man8" 1707:1733 the newly identified "Man8" (Man7+Glc) 1707:1744 Using this approach, different lots or different CHO produced mAbs was thoroughly examined and found that the newly identified "Man8" (Man7+Glc) was also present in different batches and in some commercially available therapeutic mAbs. 27291648 11 40 theme identified 1717:1726 arg1 present 1755:1761 present 1755:1761 present 1755:1761 Using this approach, different lots or different CHO produced mAbs was thoroughly examined and found that the newly identified "Man8" (Man7+Glc) was also present in different batches and in some commercially available therapeutic mAbs. 27291648 11 40 theme identified 1717:1726 arg1 Man7+Glc 1736:1743 Man7+Glc 1736:1743 Man7+Glc 1736:1743 Using this approach, different lots or different CHO produced mAbs was thoroughly examined and found that the newly identified "Man8" (Man7+Glc) was also present in different batches and in some commercially available therapeutic mAbs. 27291648 11 41 theme available 1809:1817 arg1 mAbs 1831:1834 some commercially available therapeutic mAbs 1791:1834 some commercially available therapeutic mAbs 1791:1834 Using this approach, different lots or different CHO produced mAbs was thoroughly examined and found that the newly identified "Man8" (Man7+Glc) was also present in different batches and in some commercially available therapeutic mAbs. 27291648 8 42 theme structural 1139:1148 arg1 isomer 1150:1155 structural isomer 1139:1155 structural isomer at low level 1139:1168 One such structural isomer at low level, terminal GlcNAc of G1F+GlcNAc, was identified to be linked at the 1,6 branch. 27291648 4 43 theme ion 645:647 arg1 mode 649:652 negative ion mode 636:652 negative ion mode followed by identification of the signature D ions 636:703 The glycan structure was characterized by MS(n) fragmentation in negative ion mode followed by identification of the signature D ions. 27291648 11 44 theme different 1640:1648 arg1 CHO 1650:1652 different CHO 1640:1652 different CHO 1640:1652 Using this approach, different lots or different CHO produced mAbs was thoroughly examined and found that the newly identified "Man8" (Man7+Glc) was also present in different batches and in some commercially available therapeutic mAbs. 27291648 10 45 theme disaccharides 1572:1584 arg1 cleavage 1538:1545 the cleavage 1534:1545 the cleavage of α-1,3 linked terminal disaccharides (Man+glucose) 1534:1598 The identification was further confirmed by a purified α-1,2-endomannosidase enzyme to generate the cleavage of α-1,3 linked terminal disaccharides (Man+glucose). 27291648 6 46 theme terminal 868:875 arg1 acid 884:887 terminal sialic acid 868:887 terminal sialic acid attached in the 1,6 branch at 2,3 position 868:930 The developed method successfully characterized structural isomers of A1G1F (assigned as terminal sialic acid attached in the 1,6 branch at 2,3 position), and A1G1F' (assigned as terminal sialic acid attached in the 1,3 branch at 2,3 position). 27291648 10 47 theme linked 1556:1561 arg1 Man+glucose 1587:1597 Man+glucose 1587:1597 Man+glucose 1587:1597 The identification was further confirmed by a purified α-1,2-endomannosidase enzyme to generate the cleavage of α-1,3 linked terminal disaccharides (Man+glucose). 27291648 10 47 theme linked 1556:1561 arg1 disaccharides 1572:1584 α-1,3 linked terminal disaccharides 1550:1584 α-1,3 linked terminal disaccharides (Man+glucose) 1550:1598 The identification was further confirmed by a purified α-1,2-endomannosidase enzyme to generate the cleavage of α-1,3 linked terminal disaccharides (Man+glucose). 27291648 2 48 theme antibody 299:306 arg1 glycans 263:269 N-linked glycans 254:269 N-linked glycans of a recombinant monoclonal antibody 254:306 N-linked glycans of a recombinant monoclonal antibody were released by PNGase F and labeled with 2-aminobenzamide (2-AB) fluorescent tag. 27291648 1 49 theme structural 173:182 arg1 isomers 184:190 low abundant structural isomers 160:190 low abundant structural isomers of N-linked glycans in biological therapeutics 160:237 An effective LC-MS based method for online characterization of low abundant structural isomers of N-linked glycans in biological therapeutics was developed. 27291648 8 50 theme terminal 1171:1178 arg1 One 1130:1132 One 1130:1132 One 1130:1132 One such structural isomer at low level, terminal GlcNAc of G1F+GlcNAc, was identified to be linked at the 1,6 branch. 27291648 8 50 theme terminal 1171:1178 arg1 GlcNAc 1180:1185 terminal GlcNAc 1171:1185 terminal GlcNAc of G1F+GlcNAc 1171:1199 One such structural isomer at low level, terminal GlcNAc of G1F+GlcNAc, was identified to be linked at the 1,6 branch. 27291648 7 51 theme abundant 1082:1089 arg1 species 1091:1097 previously unknown low abundant species 1059:1097 previously unknown low abundant species 1059:1097 Moreover, using the same approach, previously unknown low abundant species were identified unambiguously. 27291648 9 52 theme terminal 1420:1427 arg1 glucose 1429:1435 one terminal glucose 1416:1435 one terminal glucose 1416:1435 Additionally, another low level structural isomer, previously assigned as Man8 glycan, was found to be Man7+Glc glycan as its 1,3 branch containing three mannoses and one terminal glucose. 27291648 6 53 theme 1,3 995:997 arg1 branch 999:1004 the 1,3 branch 991:1004 the 1,3 branch at 2,3 position 991:1020 The developed method successfully characterized structural isomers of A1G1F (assigned as terminal sialic acid attached in the 1,6 branch at 2,3 position), and A1G1F' (assigned as terminal sialic acid attached in the 1,3 branch at 2,3 position). 27291648 11 54 from batches 1776:1782 arg1 " 1733:1733 the newly identified "Man8" 1707:1733 the newly identified "Man8" (Man7+Glc) 1707:1744 Using this approach, different lots or different CHO produced mAbs was thoroughly examined and found that the newly identified "Man8" (Man7+Glc) was also present in different batches and in some commercially available therapeutic mAbs. 27291648 11 54 from batches 1776:1782 arg1 present 1755:1761 present 1755:1761 present 1755:1761 Using this approach, different lots or different CHO produced mAbs was thoroughly examined and found that the newly identified "Man8" (Man7+Glc) was also present in different batches and in some commercially available therapeutic mAbs. 27291648 8 55 theme 1,6 1237:1239 arg1 branch 1241:1246 the 1,6 branch 1233:1246 the 1,6 branch 1233:1246 One such structural isomer at low level, terminal GlcNAc of G1F+GlcNAc, was identified to be linked at the 1,6 branch. 27291648 5 56 theme monosaccharide 730:743 arg1 sequence 745:752 monosaccharide sequence 730:752 monosaccharide sequence 730:752 The assignment included monosaccharide sequence and linkage information. 27291648 11 57 located present 1755:1761 arg2 present 1755:1761 present 1755:1761 present 1755:1761 Using this approach, different lots or different CHO produced mAbs was thoroughly examined and found that the newly identified "Man8" (Man7+Glc) was also present in different batches and in some commercially available therapeutic mAbs. 27291648 11 57 located present 1755:1761 arg1 batches 1776:1782 different batches 1766:1782 different batches 1766:1782 Using this approach, different lots or different CHO produced mAbs was thoroughly examined and found that the newly identified "Man8" (Man7+Glc) was also present in different batches and in some commercially available therapeutic mAbs. 27291648 11 57 located present 1755:1761 arg2 Man7+Glc 1736:1743 Man7+Glc 1736:1743 Man7+Glc 1736:1743 Using this approach, different lots or different CHO produced mAbs was thoroughly examined and found that the newly identified "Man8" (Man7+Glc) was also present in different batches and in some commercially available therapeutic mAbs. 27291648 11 57 located present 1755:1761 arg2 " 1733:1733 the newly identified "Man8" 1707:1733 the newly identified "Man8" (Man7+Glc) 1707:1744 Using this approach, different lots or different CHO produced mAbs was thoroughly examined and found that the newly identified "Man8" (Man7+Glc) was also present in different batches and in some commercially available therapeutic mAbs. 27291648 2 58 theme PNGase 325:330 arg1 F 332:332 PNGase F 325:332 PNGase F 325:332 N-linked glycans of a recombinant monoclonal antibody were released by PNGase F and labeled with 2-aminobenzamide (2-AB) fluorescent tag. 27291648 1 59 theme glycans 204:210 arg1 isomers 184:190 low abundant structural isomers 160:190 low abundant structural isomers of N-linked glycans in biological therapeutics 160:237 An effective LC-MS based method for online characterization of low abundant structural isomers of N-linked glycans in biological therapeutics was developed. 27291648 2 60 theme N-linked 254:261 arg1 glycans 263:269 N-linked glycans 254:269 N-linked glycans of a recombinant monoclonal antibody 254:306 N-linked glycans of a recombinant monoclonal antibody were released by PNGase F and labeled with 2-aminobenzamide (2-AB) fluorescent tag. 27291648 4 61 theme D 698:698 arg1 ions 700:703 the signature D ions 684:703 the signature D ions 684:703 The glycan structure was characterized by MS(n) fragmentation in negative ion mode followed by identification of the signature D ions. 27291648 1 62 theme biological 215:224 arg1 therapeutics 226:237 biological therapeutics 215:237 biological therapeutics 215:237 An effective LC-MS based method for online characterization of low abundant structural isomers of N-linked glycans in biological therapeutics was developed. 27291648 0 63 from Therapeutics 74:85 arg1 Identification 0:13 Identification 0:13 Identification of Low Abundant Isomeric N-Glycan Structures in Biological Therapeutics by LC/MS. 0:95 Identification of Low Abundant Isomeric N-Glycan Structures in Biological Therapeutics by LC/MS. 27291648 7 64 theme same 1044:1047 arg1 approach 1049:1056 the same approach 1040:1056 the same approach 1040:1056 Moreover, using the same approach, previously unknown low abundant species were identified unambiguously. 27291648 1 65 from therapeutics 226:237 arg1 isomers 184:190 low abundant structural isomers 160:190 low abundant structural isomers of N-linked glycans in biological therapeutics 160:237 An effective LC-MS based method for online characterization of low abundant structural isomers of N-linked glycans in biological therapeutics was developed. 27291648 1 66 theme based 116:120 arg1 method 122:127 An effective LC-MS based method 97:127 An effective LC-MS based method for online characterization of low abundant structural isomers of N-linked glycans in biological therapeutics 97:237 An effective LC-MS based method for online characterization of low abundant structural isomers of N-linked glycans in biological therapeutics was developed. 27291648 6 67 theme terminal 958:965 arg1 acid 974:977 terminal sialic acid 958:977 terminal sialic acid attached in the 1,3 branch at 2,3 position 958:1020 The developed method successfully characterized structural isomers of A1G1F (assigned as terminal sialic acid attached in the 1,6 branch at 2,3 position), and A1G1F' (assigned as terminal sialic acid attached in the 1,3 branch at 2,3 position). 27291648 7 68 theme unknown 1070:1076 arg1 species 1091:1097 previously unknown low abundant species 1059:1097 previously unknown low abundant species 1059:1097 Moreover, using the same approach, previously unknown low abundant species were identified unambiguously. 27291648 2 69 theme recombinant 276:286 arg1 antibody 299:306 a recombinant monoclonal antibody 274:306 a recombinant monoclonal antibody 274:306 N-linked glycans of a recombinant monoclonal antibody were released by PNGase F and labeled with 2-aminobenzamide (2-AB) fluorescent tag. 27291648 6 70 attach attached 979:986 arg3 branch 999:1004 the 1,3 branch 991:1004 the 1,3 branch at 2,3 position 991:1020 The developed method successfully characterized structural isomers of A1G1F (assigned as terminal sialic acid attached in the 1,6 branch at 2,3 position), and A1G1F' (assigned as terminal sialic acid attached in the 1,3 branch at 2,3 position). 27291648 6 70 attach attached 979:986 arg2 acid 974:977 terminal sialic acid 958:977 terminal sialic acid attached in the 1,3 branch at 2,3 position 958:1020 The developed method successfully characterized structural isomers of A1G1F (assigned as terminal sialic acid attached in the 1,6 branch at 2,3 position), and A1G1F' (assigned as terminal sialic acid attached in the 1,3 branch at 2,3 position). 27291648 8 71 attach linked 1223:1228 arg2 GlcNAc 1180:1185 terminal GlcNAc 1171:1185 terminal GlcNAc of G1F+GlcNAc 1171:1199 One such structural isomer at low level, terminal GlcNAc of G1F+GlcNAc, was identified to be linked at the 1,6 branch. 27291648 8 71 attach linked 1223:1228 arg2 One 1130:1132 One 1130:1132 One 1130:1132 One such structural isomer at low level, terminal GlcNAc of G1F+GlcNAc, was identified to be linked at the 1,6 branch. 27291648 8 71 attach linked 1223:1228 arg3 branch 1241:1246 the 1,6 branch 1233:1246 the 1,6 branch 1233:1246 One such structural isomer at low level, terminal GlcNAc of G1F+GlcNAc, was identified to be linked at the 1,6 branch. 27291648 11 72 theme Man8 1729:1732 arg1 " 1733:1733 the newly identified "Man8" 1707:1733 the newly identified "Man8" (Man7+Glc) 1707:1744 Using this approach, different lots or different CHO produced mAbs was thoroughly examined and found that the newly identified "Man8" (Man7+Glc) was also present in different batches and in some commercially available therapeutic mAbs. 27291648 11 72 theme Man8 1729:1732 arg1 present 1755:1761 present 1755:1761 present 1755:1761 Using this approach, different lots or different CHO produced mAbs was thoroughly examined and found that the newly identified "Man8" (Man7+Glc) was also present in different batches and in some commercially available therapeutic mAbs. 27291648 11 72 theme Man8 1729:1732 arg1 Man7+Glc 1736:1743 Man7+Glc 1736:1743 Man7+Glc 1736:1743 Using this approach, different lots or different CHO produced mAbs was thoroughly examined and found that the newly identified "Man8" (Man7+Glc) was also present in different batches and in some commercially available therapeutic mAbs. 27291648 9 73 theme level 1275:1279 arg1 isomer 1292:1297 another low level structural isomer 1263:1297 another low level structural isomer 1263:1297 Additionally, another low level structural isomer, previously assigned as Man8 glycan, was found to be Man7+Glc glycan as its 1,3 branch containing three mannoses and one terminal glucose. 27291648 1 74 from isomers 184:190 arg1 therapeutics 226:237 biological therapeutics 215:237 biological therapeutics 215:237 An effective LC-MS based method for online characterization of low abundant structural isomers of N-linked glycans in biological therapeutics was developed. 27291648 1 75 theme low 160:162 arg1 isomers 184:190 low abundant structural isomers 160:190 low abundant structural isomers of N-linked glycans in biological therapeutics 160:237 An effective LC-MS based method for online characterization of low abundant structural isomers of N-linked glycans in biological therapeutics was developed. 27291648 4 76 from fragmentation 619:631 arg1 mode 649:652 negative ion mode 636:652 negative ion mode followed by identification of the signature D ions 636:703 The glycan structure was characterized by MS(n) fragmentation in negative ion mode followed by identification of the signature D ions. 27291648 6 77 theme developed 783:791 arg1 method 793:798 The developed method 779:798 The developed method 779:798 The developed method successfully characterized structural isomers of A1G1F (assigned as terminal sialic acid attached in the 1,6 branch at 2,3 position), and A1G1F' (assigned as terminal sialic acid attached in the 1,3 branch at 2,3 position). 27291648 11 78 theme therapeutic 1819:1829 arg1 mAbs 1831:1834 some commercially available therapeutic mAbs 1791:1834 some commercially available therapeutic mAbs 1791:1834 Using this approach, different lots or different CHO produced mAbs was thoroughly examined and found that the newly identified "Man8" (Man7+Glc) was also present in different batches and in some commercially available therapeutic mAbs. 27291648 1 79 link N-linked 195:202 arg1 glycans 204:210 N-linked glycans 195:210 N-linked glycans in biological therapeutics 195:237 An effective LC-MS based method for online characterization of low abundant structural isomers of N-linked glycans in biological therapeutics was developed. 27291648 3 80 theme interaction 487:497 arg1 chromatography 506:519 online ultraperformance liquid chromatography-hydrophilic interaction liquid chromatography 429:519 online ultraperformance liquid chromatography-hydrophilic interaction liquid chromatography (UPLC-HILIC) coupled with mass spectrometry (MS) 429:568 The labeled glycans were analyzed by online ultraperformance liquid chromatography-hydrophilic interaction liquid chromatography (UPLC-HILIC) coupled with mass spectrometry (MS). 27291648 3 80 theme interaction 487:497 arg1 UPLC-HILIC 522:531 UPLC-HILIC 522:531 UPLC-HILIC 522:531 The labeled glycans were analyzed by online ultraperformance liquid chromatography-hydrophilic interaction liquid chromatography (UPLC-HILIC) coupled with mass spectrometry (MS). 27291648 11 81 from mAbs 1831:1834 arg1 present 1755:1761 present 1755:1761 present 1755:1761 Using this approach, different lots or different CHO produced mAbs was thoroughly examined and found that the newly identified "Man8" (Man7+Glc) was also present in different batches and in some commercially available therapeutic mAbs. 27291648 3 82 theme liquid 453:458 arg1 chromatography 506:519 online ultraperformance liquid chromatography-hydrophilic interaction liquid chromatography 429:519 online ultraperformance liquid chromatography-hydrophilic interaction liquid chromatography (UPLC-HILIC) coupled with mass spectrometry (MS) 429:568 The labeled glycans were analyzed by online ultraperformance liquid chromatography-hydrophilic interaction liquid chromatography (UPLC-HILIC) coupled with mass spectrometry (MS). 27291648 3 82 theme liquid 453:458 arg1 UPLC-HILIC 522:531 UPLC-HILIC 522:531 UPLC-HILIC 522:531 The labeled glycans were analyzed by online ultraperformance liquid chromatography-hydrophilic interaction liquid chromatography (UPLC-HILIC) coupled with mass spectrometry (MS). 27291648 0 83 theme Abundant 22:29 arg1 Structures 49:58 Low Abundant Isomeric N-Glycan Structures 18:58 Low Abundant Isomeric N-Glycan Structures in Biological Therapeutics 18:85 Identification of Low Abundant Isomeric N-Glycan Structures in Biological Therapeutics by LC/MS. 27291648 11 84 attach present 1755:1761 arg1 mAbs 1831:1834 some commercially available therapeutic mAbs 1791:1834 some commercially available therapeutic mAbs 1791:1834 Using this approach, different lots or different CHO produced mAbs was thoroughly examined and found that the newly identified "Man8" (Man7+Glc) was also present in different batches and in some commercially available therapeutic mAbs. 27291648 11 84 attach present 1755:1761 arg2 present 1755:1761 present 1755:1761 present 1755:1761 Using this approach, different lots or different CHO produced mAbs was thoroughly examined and found that the newly identified "Man8" (Man7+Glc) was also present in different batches and in some commercially available therapeutic mAbs. 27291648 11 84 attach present 1755:1761 arg1 batches 1776:1782 different batches 1766:1782 different batches 1766:1782 Using this approach, different lots or different CHO produced mAbs was thoroughly examined and found that the newly identified "Man8" (Man7+Glc) was also present in different batches and in some commercially available therapeutic mAbs. 27291648 11 84 attach present 1755:1761 arg2 Man7+Glc 1736:1743 Man7+Glc 1736:1743 Man7+Glc 1736:1743 Using this approach, different lots or different CHO produced mAbs was thoroughly examined and found that the newly identified "Man8" (Man7+Glc) was also present in different batches and in some commercially available therapeutic mAbs. 27291648 11 84 attach present 1755:1761 arg2 " 1733:1733 the newly identified "Man8" 1707:1733 the newly identified "Man8" (Man7+Glc) 1707:1744 Using this approach, different lots or different CHO produced mAbs was thoroughly examined and found that the newly identified "Man8" (Man7+Glc) was also present in different batches and in some commercially available therapeutic mAbs. 27291648 1 85 theme effective 100:108 arg1 method 122:127 An effective LC-MS based method 97:127 An effective LC-MS based method for online characterization of low abundant structural isomers of N-linked glycans in biological therapeutics 97:237 An effective LC-MS based method for online characterization of low abundant structural isomers of N-linked glycans in biological therapeutics was developed. 27291648 4 86 theme MS 613:614 arg1 fragmentation 619:631 MS(n) fragmentation 613:631 MS(n) fragmentation in negative ion mode followed by identification of the signature D ions 613:703 The glycan structure was characterized by MS(n) fragmentation in negative ion mode followed by identification of the signature D ions. 27291648 0 87 theme N-Glycan 40:47 arg1 Structures 49:58 Low Abundant Isomeric N-Glycan Structures 18:58 Low Abundant Isomeric N-Glycan Structures in Biological Therapeutics 18:85 Identification of Low Abundant Isomeric N-Glycan Structures in Biological Therapeutics by LC/MS. 27291648 3 88 theme online 429:434 arg1 chromatography 506:519 online ultraperformance liquid chromatography-hydrophilic interaction liquid chromatography 429:519 online ultraperformance liquid chromatography-hydrophilic interaction liquid chromatography (UPLC-HILIC) coupled with mass spectrometry (MS) 429:568 The labeled glycans were analyzed by online ultraperformance liquid chromatography-hydrophilic interaction liquid chromatography (UPLC-HILIC) coupled with mass spectrometry (MS). 27291648 3 88 theme online 429:434 arg1 UPLC-HILIC 522:531 UPLC-HILIC 522:531 UPLC-HILIC 522:531 The labeled glycans were analyzed by online ultraperformance liquid chromatography-hydrophilic interaction liquid chromatography (UPLC-HILIC) coupled with mass spectrometry (MS). 27291648 6 89 theme structural 827:836 arg1 isomers 838:844 structural isomers 827:844 structural isomers of A1G1F (assigned as terminal sialic acid attached in the 1,6 branch at 2,3 position), and A1G1F' (assigned as terminal sialic acid attached in the 1,3 branch at 2,3 position) 827:1021 The developed method successfully characterized structural isomers of A1G1F (assigned as terminal sialic acid attached in the 1,6 branch at 2,3 position), and A1G1F' (assigned as terminal sialic acid attached in the 1,3 branch at 2,3 position). 27291648 6 90 theme 1,6 905:907 arg1 branch 909:914 the 1,6 branch 901:914 the 1,6 branch at 2,3 position 901:930 The developed method successfully characterized structural isomers of A1G1F (assigned as terminal sialic acid attached in the 1,6 branch at 2,3 position), and A1G1F' (assigned as terminal sialic acid attached in the 1,3 branch at 2,3 position). 27291648 3 91 theme mass 547:550 arg1 MS 566:567 MS 566:567 MS 566:567 The labeled glycans were analyzed by online ultraperformance liquid chromatography-hydrophilic interaction liquid chromatography (UPLC-HILIC) coupled with mass spectrometry (MS). 27291648 3 91 theme mass 547:550 arg1 spectrometry 552:563 mass spectrometry 547:563 mass spectrometry (MS) 547:568 The labeled glycans were analyzed by online ultraperformance liquid chromatography-hydrophilic interaction liquid chromatography (UPLC-HILIC) coupled with mass spectrometry (MS). 27291648 9 92 theme Man7+Glc 1352:1359 arg1 glycan 1361:1366 Man7+Glc glycan 1352:1366 Man7+Glc glycan 1352:1366 Additionally, another low level structural isomer, previously assigned as Man8 glycan, was found to be Man7+Glc glycan as its 1,3 branch containing three mannoses and one terminal glucose. 27291648 4 93 theme negative 636:643 arg1 mode 649:652 negative ion mode 636:652 negative ion mode followed by identification of the signature D ions 636:703 The glycan structure was characterized by MS(n) fragmentation in negative ion mode followed by identification of the signature D ions. 27291648 10 94 theme purified 1484:1491 arg1 enzyme 1515:1520 a purified α-1,2-endomannosidase enzyme 1482:1520 a purified α-1,2-endomannosidase enzyme to generate the cleavage of α-1,3 linked terminal disaccharides (Man+glucose) 1482:1598 The identification was further confirmed by a purified α-1,2-endomannosidase enzyme to generate the cleavage of α-1,3 linked terminal disaccharides (Man+glucose). 27291648 10 95 link linked 1556:1561 arg1 Man+glucose 1587:1597 Man+glucose 1587:1597 Man+glucose 1587:1597 The identification was further confirmed by a purified α-1,2-endomannosidase enzyme to generate the cleavage of α-1,3 linked terminal disaccharides (Man+glucose). 27291648 10 95 link linked 1556:1561 arg1 disaccharides 1572:1584 α-1,3 linked terminal disaccharides 1550:1584 α-1,3 linked terminal disaccharides (Man+glucose) 1550:1598 The identification was further confirmed by a purified α-1,2-endomannosidase enzyme to generate the cleavage of α-1,3 linked terminal disaccharides (Man+glucose). 27291648 6 96 attach attached 889:896 arg2 acid 884:887 terminal sialic acid 868:887 terminal sialic acid attached in the 1,6 branch at 2,3 position 868:930 The developed method successfully characterized structural isomers of A1G1F (assigned as terminal sialic acid attached in the 1,6 branch at 2,3 position), and A1G1F' (assigned as terminal sialic acid attached in the 1,3 branch at 2,3 position). 27291648 6 96 attach attached 889:896 arg3 branch 909:914 the 1,6 branch 901:914 the 1,6 branch at 2,3 position 901:930 The developed method successfully characterized structural isomers of A1G1F (assigned as terminal sialic acid attached in the 1,6 branch at 2,3 position), and A1G1F' (assigned as terminal sialic acid attached in the 1,3 branch at 2,3 position). 27291648 8 97 from level 1164:1168 arg1 isomer 1150:1155 structural isomer 1139:1155 structural isomer at low level 1139:1168 One such structural isomer at low level, terminal GlcNAc of G1F+GlcNAc, was identified to be linked at the 1,6 branch. 27291648 2 98 theme fluorescent 375:385 arg1 tag 387:389 2-aminobenzamide (2-AB) fluorescent tag 351:389 2-aminobenzamide (2-AB) fluorescent tag 351:389 N-linked glycans of a recombinant monoclonal antibody were released by PNGase F and labeled with 2-aminobenzamide (2-AB) fluorescent tag. 27291648 9 99 theme 1,3 1375:1377 arg1 branch 1379:1384 its 1,3 branch 1371:1384 its 1,3 branch containing three mannoses 1371:1410 Additionally, another low level structural isomer, previously assigned as Man8 glycan, was found to be Man7+Glc glycan as its 1,3 branch containing three mannoses and one terminal glucose. 25625759 2 0 link N‑linked 351:358 arg1 oligosaccharides 360:375 complex N‑linked oligosaccharides 343:375 complex N‑linked oligosaccharides containing poly‑N‑acetyllactosamine (polylactosamine) chains, which have previously been reported to inhibit 3'‑azidothymidine (AZT) 343:508 Of particular importance in tumor growth and invasion, is the synthesis of complex N‑linked oligosaccharides containing poly‑N‑acetyllactosamine (polylactosamine) chains, which have previously been reported to inhibit 3'‑azidothymidine (AZT). 25625759 2 1 theme polylactosamine 414:428 arg1 chains 431:436 poly‑N‑acetyllactosamine (polylactosamine) chains 388:436 poly‑N‑acetyllactosamine (polylactosamine) chains 388:436 Of particular importance in tumor growth and invasion, is the synthesis of complex N‑linked oligosaccharides containing poly‑N‑acetyllactosamine (polylactosamine) chains, which have previously been reported to inhibit 3'‑azidothymidine (AZT). 25625759 2 2 contain containing 377:386 arg2 chains 431:436 poly‑N‑acetyllactosamine (polylactosamine) chains 388:436 poly‑N‑acetyllactosamine (polylactosamine) chains 388:436 Of particular importance in tumor growth and invasion, is the synthesis of complex N‑linked oligosaccharides containing poly‑N‑acetyllactosamine (polylactosamine) chains, which have previously been reported to inhibit 3'‑azidothymidine (AZT). 25625759 2 2 contain containing 377:386 arg1 oligosaccharides 360:375 complex N‑linked oligosaccharides 343:375 complex N‑linked oligosaccharides containing poly‑N‑acetyllactosamine (polylactosamine) chains, which have previously been reported to inhibit 3'‑azidothymidine (AZT) 343:508 Of particular importance in tumor growth and invasion, is the synthesis of complex N‑linked oligosaccharides containing poly‑N‑acetyllactosamine (polylactosamine) chains, which have previously been reported to inhibit 3'‑azidothymidine (AZT). 25625759 8 3 theme HG‑CD147 1616:1623 arg1 N‑glycans 1603:1611 the N‑glycans 1599:1611 the N‑glycans of HG‑CD147 1599:1623 Thus, AZT is suggested to be an antineoplastic drug, which may be effective therapeutically for certain types of cancer through acting on the N‑glycans of HG‑CD147. 25625759 5 4 theme MMP2 1026:1029 arg1 expression 1012:1021 the expression 1008:1021 the expression of MMP2 1008:1029 Subsequent to treatment with various concentrations of AZT, the N‑glycans of highly glycosylated (HG)‑CD147 were observed to decrease in the two cell lines, and the expression of MMP2 was also significantly decreased. 25625759 4 5 from CD147 808:812 arg1 SGC‑7901 817:824 SGC‑7901 817:824 SGC‑7901 817:824 The present study aimed to explore the mechanism by which AZT may affect matrix metalloproteinase‑2 (MMP2) expression and the cell cycle via regulation of the N‑glycans on CD147 in SGC‑7901 and U251 cell lines. 25625759 4 5 from CD147 808:812 arg1 lines 840:844 U251 cell lines 830:844 U251 cell lines 830:844 The present study aimed to explore the mechanism by which AZT may affect matrix metalloproteinase‑2 (MMP2) expression and the cell cycle via regulation of the N‑glycans on CD147 in SGC‑7901 and U251 cell lines. 25625759 4 5 from CD147 808:812 arg1 regulation 777:786 regulation 777:786 regulation of the N‑glycans on CD147 in SGC‑7901 and U251 cell lines 777:844 The present study aimed to explore the mechanism by which AZT may affect matrix metalloproteinase‑2 (MMP2) expression and the cell cycle via regulation of the N‑glycans on CD147 in SGC‑7901 and U251 cell lines. 25625759 3 6 gly glycoprotein 555:566 arg1 Cluster 511:517 Cluster 511:517 Cluster of differentiation 147 (CD147) 511:548 Cluster of differentiation 147 (CD147) is a glycoprotein that carries β1,6‑branched polylactosamine sugars on its N‑glycans. 25625759 3 6 gly glycoprotein 555:566 arg1 glycoprotein 555:566 a glycoprotein 553:566 a glycoprotein that carries β1,6‑branched polylactosamine sugars on its N‑glycans 553:633 Cluster of differentiation 147 (CD147) is a glycoprotein that carries β1,6‑branched polylactosamine sugars on its N‑glycans. 25625759 7 7 theme cell 1414:1417 arg1 proliferation 1419:1431 cell proliferation 1414:1431 cell proliferation 1414:1431 It was suggested that AZT may reduce the biosynthesis of polylactosamine chains on CD147 and reduce MMP2 expression to inhibit cell proliferation in SGC‑7901 and U251 cells. 25625759 4 8 theme N‑glycans 795:803 arg1 regulation 777:786 regulation 777:786 regulation of the N‑glycans on CD147 in SGC‑7901 and U251 cell lines 777:844 The present study aimed to explore the mechanism by which AZT may affect matrix metalloproteinase‑2 (MMP2) expression and the cell cycle via regulation of the N‑glycans on CD147 in SGC‑7901 and U251 cell lines. 25625759 3 9 theme polylactosamine 595:609 arg1 sugars 611:616 β1,6‑branched polylactosamine sugars 581:616 β1,6‑branched polylactosamine sugars on its N‑glycans 581:633 Cluster of differentiation 147 (CD147) is a glycoprotein that carries β1,6‑branched polylactosamine sugars on its N‑glycans. 25625759 3 10 theme differentiation 147 522:540 arg1 glycoprotein 555:566 a glycoprotein 553:566 a glycoprotein that carries β1,6‑branched polylactosamine sugars on its N‑glycans 553:633 Cluster of differentiation 147 (CD147) is a glycoprotein that carries β1,6‑branched polylactosamine sugars on its N‑glycans. 25625759 3 10 theme differentiation 147 522:540 arg1 Cluster 511:517 Cluster 511:517 Cluster of differentiation 147 (CD147) 511:548 Cluster of differentiation 147 (CD147) is a glycoprotein that carries β1,6‑branched polylactosamine sugars on its N‑glycans. 25625759 0 11 theme metalloproteinase-2 129:147 arg1 expression 149:158 matrix metalloproteinase-2 expression 122:158 matrix metalloproteinase-2 expression in SGC-7901 and U251 cells 122:185 3'-Azidothymidine may potently inhibit the biosynthesis of polylactosamine chains on highly glycosylated-CD147 and reduce matrix metalloproteinase-2 expression in SGC-7901 and U251 cells. 25625759 4 12 from N‑glycans 795:803 arg1 CD147 808:812 CD147 808:812 CD147 in SGC‑7901 and U251 cell lines 808:844 The present study aimed to explore the mechanism by which AZT may affect matrix metalloproteinase‑2 (MMP2) expression and the cell cycle via regulation of the N‑glycans on CD147 in SGC‑7901 and U251 cell lines. 25625759 6 13 theme cell 1078:1081 arg1 analysis 1089:1096 cell cycle analysis 1078:1096 cell cycle analysis 1078:1096 In addition, cell cycle analysis demonstrated that the percentage of the cells in the G1 phase increased in a dose‑dependent manner with AZT treatment, indicating that AZT may inhibit cell proliferation in SGC‑7901 cells. 25625759 0 14 theme matrix 122:127 arg1 metalloproteinase-2 129:147 matrix metalloproteinase-2 122:147 matrix metalloproteinase-2 expression in SGC-7901 and U251 cells 122:185 3'-Azidothymidine may potently inhibit the biosynthesis of polylactosamine chains on highly glycosylated-CD147 and reduce matrix metalloproteinase-2 expression in SGC-7901 and U251 cells. 25625759 0 15 from biosynthesis 43:54 arg1 glycosylated-CD147 92:109 glycosylated-CD147 92:109 glycosylated-CD147 92:109 3'-Azidothymidine may potently inhibit the biosynthesis of polylactosamine chains on highly glycosylated-CD147 and reduce matrix metalloproteinase-2 expression in SGC-7901 and U251 cells. 25625759 1 16 theme N‑linked 203:210 arg1 glycans 212:218 N‑linked glycans 203:218 N‑linked glycans 203:218 Alterations to N‑linked glycans are closely associated with cancer progression. 25625759 7 17 theme MMP2 1387:1390 arg1 expression 1392:1401 MMP2 expression 1387:1401 MMP2 expression 1387:1401 It was suggested that AZT may reduce the biosynthesis of polylactosamine chains on CD147 and reduce MMP2 expression to inhibit cell proliferation in SGC‑7901 and U251 cells. 25625759 8 18 theme certain 1557:1563 arg1 types 1565:1569 certain types 1557:1569 certain types of cancer 1557:1579 Thus, AZT is suggested to be an antineoplastic drug, which may be effective therapeutically for certain types of cancer through acting on the N‑glycans of HG‑CD147. 25625759 6 19 theme cell 1249:1252 arg1 proliferation 1254:1266 cell proliferation 1249:1266 cell proliferation 1249:1266 In addition, cell cycle analysis demonstrated that the percentage of the cells in the G1 phase increased in a dose‑dependent manner with AZT treatment, indicating that AZT may inhibit cell proliferation in SGC‑7901 cells. 25625759 2 20 theme complex 343:349 arg1 oligosaccharides 360:375 complex N‑linked oligosaccharides 343:375 complex N‑linked oligosaccharides containing poly‑N‑acetyllactosamine (polylactosamine) chains, which have previously been reported to inhibit 3'‑azidothymidine (AZT) 343:508 Of particular importance in tumor growth and invasion, is the synthesis of complex N‑linked oligosaccharides containing poly‑N‑acetyllactosamine (polylactosamine) chains, which have previously been reported to inhibit 3'‑azidothymidine (AZT). 25625759 4 21 theme metalloproteinase‑2 716:734 arg1 expression 743:752 matrix metalloproteinase‑2 (MMP2) expression 709:752 matrix metalloproteinase‑2 (MMP2) expression 709:752 The present study aimed to explore the mechanism by which AZT may affect matrix metalloproteinase‑2 (MMP2) expression and the cell cycle via regulation of the N‑glycans on CD147 in SGC‑7901 and U251 cell lines. 25625759 1 22 link N‑linked 203:210 arg1 glycans 212:218 N‑linked glycans 203:218 N‑linked glycans 203:218 Alterations to N‑linked glycans are closely associated with cancer progression. 25625759 4 23 from regulation 777:786 arg1 CD147 808:812 CD147 808:812 CD147 in SGC‑7901 and U251 cell lines 808:844 The present study aimed to explore the mechanism by which AZT may affect matrix metalloproteinase‑2 (MMP2) expression and the cell cycle via regulation of the N‑glycans on CD147 in SGC‑7901 and U251 cell lines. 25625759 5 24 with treatment 861:869 arg1 various concentrations 876:897 various concentrations 876:897 various concentrations of AZT 876:904 Subsequent to treatment with various concentrations of AZT, the N‑glycans of highly glycosylated (HG)‑CD147 were observed to decrease in the two cell lines, and the expression of MMP2 was also significantly decreased. 25625759 4 25 theme matrix 709:714 arg1 expression 743:752 matrix metalloproteinase‑2 (MMP2) expression 709:752 matrix metalloproteinase‑2 (MMP2) expression 709:752 The present study aimed to explore the mechanism by which AZT may affect matrix metalloproteinase‑2 (MMP2) expression and the cell cycle via regulation of the N‑glycans on CD147 in SGC‑7901 and U251 cell lines. 25625759 7 26 theme polylactosamine 1344:1358 arg1 chains 1360:1365 polylactosamine chains 1344:1365 polylactosamine chains 1344:1365 It was suggested that AZT may reduce the biosynthesis of polylactosamine chains on CD147 and reduce MMP2 expression to inhibit cell proliferation in SGC‑7901 and U251 cells. 25625759 7 27 theme chains 1360:1365 arg1 biosynthesis 1328:1339 the biosynthesis 1324:1339 the biosynthesis of polylactosamine chains on CD147 1324:1374 It was suggested that AZT may reduce the biosynthesis of polylactosamine chains on CD147 and reduce MMP2 expression to inhibit cell proliferation in SGC‑7901 and U251 cells. 25625759 6 28 theme G1 1151:1152 arg1 phase 1154:1158 the G1 phase 1147:1158 the G1 phase 1147:1158 In addition, cell cycle analysis demonstrated that the percentage of the cells in the G1 phase increased in a dose‑dependent manner with AZT treatment, indicating that AZT may inhibit cell proliferation in SGC‑7901 cells. 25625759 2 29 from importance 282:291 arg1 invasion 313:320 invasion 313:320 invasion 313:320 Of particular importance in tumor growth and invasion, is the synthesis of complex N‑linked oligosaccharides containing poly‑N‑acetyllactosamine (polylactosamine) chains, which have previously been reported to inhibit 3'‑azidothymidine (AZT). 25625759 2 29 from importance 282:291 arg1 growth 302:307 tumor growth 296:307 tumor growth 296:307 Of particular importance in tumor growth and invasion, is the synthesis of complex N‑linked oligosaccharides containing poly‑N‑acetyllactosamine (polylactosamine) chains, which have previously been reported to inhibit 3'‑azidothymidine (AZT). 25625759 5 30 dep glycosylated 931:942 arg1 HG 945:946 HG 945:946 HG 945:946 Subsequent to treatment with various concentrations of AZT, the N‑glycans of highly glycosylated (HG)‑CD147 were observed to decrease in the two cell lines, and the expression of MMP2 was also significantly decreased. 25625759 2 31 from growth 302:307 arg1 synthesis 330:338 the synthesis 326:338 the synthesis of complex N‑linked oligosaccharides containing poly‑N‑acetyllactosamine (polylactosamine) chains, which have previously been reported to inhibit 3'‑azidothymidine (AZT) 326:508 Of particular importance in tumor growth and invasion, is the synthesis of complex N‑linked oligosaccharides containing poly‑N‑acetyllactosamine (polylactosamine) chains, which have previously been reported to inhibit 3'‑azidothymidine (AZT). 25625759 6 32 theme cells 1138:1142 arg1 percentage 1120:1129 the percentage 1116:1129 the percentage of the cells in the G1 phase 1116:1158 In addition, cell cycle analysis demonstrated that the percentage of the cells in the G1 phase increased in a dose‑dependent manner with AZT treatment, indicating that AZT may inhibit cell proliferation in SGC‑7901 cells. 25625759 2 33 theme particular 271:280 arg1 importance 282:291 particular importance 271:291 particular importance in tumor growth and invasion 271:320 Of particular importance in tumor growth and invasion, is the synthesis of complex N‑linked oligosaccharides containing poly‑N‑acetyllactosamine (polylactosamine) chains, which have previously been reported to inhibit 3'‑azidothymidine (AZT). 25625759 6 34 from phase 1154:1158 arg1 percentage 1120:1129 the percentage 1116:1129 the percentage of the cells in the G1 phase 1116:1158 In addition, cell cycle analysis demonstrated that the percentage of the cells in the G1 phase increased in a dose‑dependent manner with AZT treatment, indicating that AZT may inhibit cell proliferation in SGC‑7901 cells. 25625759 3 35 from sugars 611:616 arg1 N‑glycans 625:633 its N‑glycans 621:633 its N‑glycans 621:633 Cluster of differentiation 147 (CD147) is a glycoprotein that carries β1,6‑branched polylactosamine sugars on its N‑glycans. 25625759 3 36 contain carries 573:579 arg1 Cluster 511:517 Cluster 511:517 Cluster of differentiation 147 (CD147) 511:548 Cluster of differentiation 147 (CD147) is a glycoprotein that carries β1,6‑branched polylactosamine sugars on its N‑glycans. 25625759 3 36 contain carries 573:579 arg2 sugars 611:616 β1,6‑branched polylactosamine sugars 581:616 β1,6‑branched polylactosamine sugars on its N‑glycans 581:633 Cluster of differentiation 147 (CD147) is a glycoprotein that carries β1,6‑branched polylactosamine sugars on its N‑glycans. 25625759 3 36 contain carries 573:579 arg1 glycoprotein 555:566 a glycoprotein 553:566 a glycoprotein that carries β1,6‑branched polylactosamine sugars on its N‑glycans 553:633 Cluster of differentiation 147 (CD147) is a glycoprotein that carries β1,6‑branched polylactosamine sugars on its N‑glycans. 25625759 0 37 theme SGC-7901 163:170 arg1 cells 181:185 SGC-7901 and U251 cells 163:185 SGC-7901 and U251 cells 163:185 3'-Azidothymidine may potently inhibit the biosynthesis of polylactosamine chains on highly glycosylated-CD147 and reduce matrix metalloproteinase-2 expression in SGC-7901 and U251 cells. 25625759 1 38 theme cancer 248:253 arg1 progression 255:265 cancer progression 248:265 cancer progression 248:265 Alterations to N‑linked glycans are closely associated with cancer progression. 25625759 0 39 theme polylactosamine 59:73 arg1 chains 75:80 polylactosamine chains 59:80 polylactosamine chains 59:80 3'-Azidothymidine may potently inhibit the biosynthesis of polylactosamine chains on highly glycosylated-CD147 and reduce matrix metalloproteinase-2 expression in SGC-7901 and U251 cells. 25625759 8 40 theme cancer 1574:1579 arg1 types 1565:1569 certain types 1557:1569 certain types of cancer 1557:1579 Thus, AZT is suggested to be an antineoplastic drug, which may be effective therapeutically for certain types of cancer through acting on the N‑glycans of HG‑CD147. 25625759 5 41 gly glycosylated 931:942 arg1 ‑CD147 948:953 highly glycosylated (HG)‑CD147 924:953 highly glycosylated (HG)‑CD147 924:953 Subsequent to treatment with various concentrations of AZT, the N‑glycans of highly glycosylated (HG)‑CD147 were observed to decrease in the two cell lines, and the expression of MMP2 was also significantly decreased. 25625759 5 42 theme cell 992:995 arg1 lines 997:1001 the two cell lines 984:1001 the two cell lines 984:1001 Subsequent to treatment with various concentrations of AZT, the N‑glycans of highly glycosylated (HG)‑CD147 were observed to decrease in the two cell lines, and the expression of MMP2 was also significantly decreased. 25625759 8 43 theme antineoplastic 1493:1506 arg1 drug 1508:1511 an antineoplastic drug 1490:1511 an antineoplastic drug 1490:1511 Thus, AZT is suggested to be an antineoplastic drug, which may be effective therapeutically for certain types of cancer through acting on the N‑glycans of HG‑CD147. 25625759 8 43 theme antineoplastic 1493:1506 arg1 AZT 1467:1469 AZT 1467:1469 AZT 1467:1469 Thus, AZT is suggested to be an antineoplastic drug, which may be effective therapeutically for certain types of cancer through acting on the N‑glycans of HG‑CD147. 25625759 8 43 theme antineoplastic 1493:1506 arg1 effective 1527:1535 effective 1527:1535 effective 1527:1535 Thus, AZT is suggested to be an antineoplastic drug, which may be effective therapeutically for certain types of cancer through acting on the N‑glycans of HG‑CD147. 25625759 2 44 theme poly‑N‑acetyllactosamine 388:411 arg1 chains 431:436 poly‑N‑acetyllactosamine (polylactosamine) chains 388:436 poly‑N‑acetyllactosamine (polylactosamine) chains 388:436 Of particular importance in tumor growth and invasion, is the synthesis of complex N‑linked oligosaccharides containing poly‑N‑acetyllactosamine (polylactosamine) chains, which have previously been reported to inhibit 3'‑azidothymidine (AZT). 25625759 6 45 theme dose‑dependent 1175:1188 arg1 manner 1190:1195 a dose‑dependent manner 1173:1195 a dose‑dependent manner 1173:1195 In addition, cell cycle analysis demonstrated that the percentage of the cells in the G1 phase increased in a dose‑dependent manner with AZT treatment, indicating that AZT may inhibit cell proliferation in SGC‑7901 cells. 25625759 0 46 theme U251 176:179 arg1 cells 181:185 SGC-7901 and U251 cells 163:185 SGC-7901 and U251 cells 163:185 3'-Azidothymidine may potently inhibit the biosynthesis of polylactosamine chains on highly glycosylated-CD147 and reduce matrix metalloproteinase-2 expression in SGC-7901 and U251 cells. 25625759 5 47 theme ‑CD147 948:953 arg1 N‑glycans 911:919 the N‑glycans 907:919 the N‑glycans of highly glycosylated (HG)‑CD147 907:953 Subsequent to treatment with various concentrations of AZT, the N‑glycans of highly glycosylated (HG)‑CD147 were observed to decrease in the two cell lines, and the expression of MMP2 was also significantly decreased. 25625759 2 48 from invasion 313:320 arg1 synthesis 330:338 the synthesis 326:338 the synthesis of complex N‑linked oligosaccharides containing poly‑N‑acetyllactosamine (polylactosamine) chains, which have previously been reported to inhibit 3'‑azidothymidine (AZT) 326:508 Of particular importance in tumor growth and invasion, is the synthesis of complex N‑linked oligosaccharides containing poly‑N‑acetyllactosamine (polylactosamine) chains, which have previously been reported to inhibit 3'‑azidothymidine (AZT). 25625759 4 49 theme U251 cell 830:838 arg1 lines 840:844 U251 cell lines 830:844 U251 cell lines 830:844 The present study aimed to explore the mechanism by which AZT may affect matrix metalloproteinase‑2 (MMP2) expression and the cell cycle via regulation of the N‑glycans on CD147 in SGC‑7901 and U251 cell lines. 25625759 6 50 from cells 1138:1142 arg1 phase 1154:1158 the G1 phase 1147:1158 the G1 phase 1147:1158 In addition, cell cycle analysis demonstrated that the percentage of the cells in the G1 phase increased in a dose‑dependent manner with AZT treatment, indicating that AZT may inhibit cell proliferation in SGC‑7901 cells. 25625759 2 51 theme oligosaccharides 360:375 arg1 synthesis 330:338 the synthesis 326:338 the synthesis of complex N‑linked oligosaccharides containing poly‑N‑acetyllactosamine (polylactosamine) chains, which have previously been reported to inhibit 3'‑azidothymidine (AZT) 326:508 Of particular importance in tumor growth and invasion, is the synthesis of complex N‑linked oligosaccharides containing poly‑N‑acetyllactosamine (polylactosamine) chains, which have previously been reported to inhibit 3'‑azidothymidine (AZT). 25625759 7 52 from biosynthesis 1328:1339 arg1 CD147 1370:1374 CD147 1370:1374 CD147 1370:1374 It was suggested that AZT may reduce the biosynthesis of polylactosamine chains on CD147 and reduce MMP2 expression to inhibit cell proliferation in SGC‑7901 and U251 cells. 25625759 2 53 theme tumor 296:300 arg1 growth 302:307 tumor growth 296:307 tumor growth 296:307 Of particular importance in tumor growth and invasion, is the synthesis of complex N‑linked oligosaccharides containing poly‑N‑acetyllactosamine (polylactosamine) chains, which have previously been reported to inhibit 3'‑azidothymidine (AZT). 25625759 2 54 theme N‑linked 351:358 arg1 oligosaccharides 360:375 complex N‑linked oligosaccharides 343:375 complex N‑linked oligosaccharides containing poly‑N‑acetyllactosamine (polylactosamine) chains, which have previously been reported to inhibit 3'‑azidothymidine (AZT) 343:508 Of particular importance in tumor growth and invasion, is the synthesis of complex N‑linked oligosaccharides containing poly‑N‑acetyllactosamine (polylactosamine) chains, which have previously been reported to inhibit 3'‑azidothymidine (AZT). 25625759 4 55 theme cell 762:765 arg1 cycle 767:771 the cell cycle 758:771 the cell cycle 758:771 The present study aimed to explore the mechanism by which AZT may affect matrix metalloproteinase‑2 (MMP2) expression and the cell cycle via regulation of the N‑glycans on CD147 in SGC‑7901 and U251 cell lines. 25625759 5 56 theme AZT 902:904 arg1 various concentrations 876:897 various concentrations 876:897 various concentrations of AZT 876:904 Subsequent to treatment with various concentrations of AZT, the N‑glycans of highly glycosylated (HG)‑CD147 were observed to decrease in the two cell lines, and the expression of MMP2 was also significantly decreased. 25625759 6 57 theme AZT 1202:1204 arg1 treatment 1206:1214 AZT treatment 1202:1214 AZT treatment 1202:1214 In addition, cell cycle analysis demonstrated that the percentage of the cells in the G1 phase increased in a dose‑dependent manner with AZT treatment, indicating that AZT may inhibit cell proliferation in SGC‑7901 cells. 25625759 4 58 theme MMP2 737:740 arg1 expression 743:752 matrix metalloproteinase‑2 (MMP2) expression 709:752 matrix metalloproteinase‑2 (MMP2) expression 709:752 The present study aimed to explore the mechanism by which AZT may affect matrix metalloproteinase‑2 (MMP2) expression and the cell cycle via regulation of the N‑glycans on CD147 in SGC‑7901 and U251 cell lines. 25625759 6 59 theme cycle 1083:1087 arg1 analysis 1089:1096 cell cycle analysis 1078:1096 cell cycle analysis 1078:1096 In addition, cell cycle analysis demonstrated that the percentage of the cells in the G1 phase increased in a dose‑dependent manner with AZT treatment, indicating that AZT may inhibit cell proliferation in SGC‑7901 cells. 25625759 4 60 theme present 640:646 arg1 study 648:652 The present study 636:652 The present study 636:652 The present study aimed to explore the mechanism by which AZT may affect matrix metalloproteinase‑2 (MMP2) expression and the cell cycle via regulation of the N‑glycans on CD147 in SGC‑7901 and U251 cell lines. 25625759 0 61 theme chains 75:80 arg1 biosynthesis 43:54 the biosynthesis 39:54 the biosynthesis of polylactosamine chains on highly glycosylated-CD147 39:109 3'-Azidothymidine may potently inhibit the biosynthesis of polylactosamine chains on highly glycosylated-CD147 and reduce matrix metalloproteinase-2 expression in SGC-7901 and U251 cells. 25625759 3 62 theme β1,6‑branched 581:593 arg1 sugars 611:616 β1,6‑branched polylactosamine sugars 581:616 β1,6‑branched polylactosamine sugars on its N‑glycans 581:633 Cluster of differentiation 147 (CD147) is a glycoprotein that carries β1,6‑branched polylactosamine sugars on its N‑glycans. 25625759 2 63 theme importance 282:291 arg1 synthesis 330:338 the synthesis 326:338 the synthesis of complex N‑linked oligosaccharides containing poly‑N‑acetyllactosamine (polylactosamine) chains, which have previously been reported to inhibit 3'‑azidothymidine (AZT) 326:508 Of particular importance in tumor growth and invasion, is the synthesis of complex N‑linked oligosaccharides containing poly‑N‑acetyllactosamine (polylactosamine) chains, which have previously been reported to inhibit 3'‑azidothymidine (AZT). 25625759 6 64 from percentage 1120:1129 arg1 phase 1154:1158 the G1 phase 1147:1158 the G1 phase 1147:1158 In addition, cell cycle analysis demonstrated that the percentage of the cells in the G1 phase increased in a dose‑dependent manner with AZT treatment, indicating that AZT may inhibit cell proliferation in SGC‑7901 cells. 25625759 5 65 theme glycosylated 931:942 arg1 ‑CD147 948:953 highly glycosylated (HG)‑CD147 924:953 highly glycosylated (HG)‑CD147 924:953 Subsequent to treatment with various concentrations of AZT, the N‑glycans of highly glycosylated (HG)‑CD147 were observed to decrease in the two cell lines, and the expression of MMP2 was also significantly decreased. 25625759 2 66 from synthesis 330:338 arg1 invasion 313:320 invasion 313:320 invasion 313:320 Of particular importance in tumor growth and invasion, is the synthesis of complex N‑linked oligosaccharides containing poly‑N‑acetyllactosamine (polylactosamine) chains, which have previously been reported to inhibit 3'‑azidothymidine (AZT). 25625759 2 66 from synthesis 330:338 arg1 growth 302:307 tumor growth 296:307 tumor growth 296:307 Of particular importance in tumor growth and invasion, is the synthesis of complex N‑linked oligosaccharides containing poly‑N‑acetyllactosamine (polylactosamine) chains, which have previously been reported to inhibit 3'‑azidothymidine (AZT). 25625759 0 67 from expression 149:158 arg1 cells 181:185 SGC-7901 and U251 cells 163:185 SGC-7901 and U251 cells 163:185 3'-Azidothymidine may potently inhibit the biosynthesis of polylactosamine chains on highly glycosylated-CD147 and reduce matrix metalloproteinase-2 expression in SGC-7901 and U251 cells. 27784219 8 0 theme lipid 1178:1182 arg1 rafts 1184:1188 lipid rafts 1178:1188 lipid rafts 1178:1188 This is unexpected since BACE1 is localized mainly in lipid rafts while ADAM10 is localized mainly in nonlipid raft domains. 27784219 9 1 theme lipid 1318:1322 arg1 composition 1324:1334 the lipid composition 1314:1334 the lipid composition of the membrane which can alter the localization of ADAM10 and BACE1 1314:1403 We hypothesized that serum deprivation results in alterations in the lipid composition of the membrane which can alter the localization of ADAM10 and BACE1. 27784219 10 2 theme cholesterol 1477:1487 arg1 extraction 1454:1463 extraction 1454:1463 extraction of membrane cholesterol following incubation with methyl β cyclodextrin 1454:1535 In support, we obtained results indicating that extraction of membrane cholesterol following incubation with methyl β cyclodextrin potentiated the effect of serum deprivation. 27784219 11 3 theme length 1670:1675 arg1 APP 1677:1679 immunoprecipiated full length APP 1647:1679 immunoprecipiated full length APP 1647:1679 Secreted BACE1 was also found to be enzymatically active towards immunoprecipiated full length APP. 27784219 2 4 theme peptides 303:310 arg1 formation 281:289 the formation 277:289 the formation of toxic Aβ peptides 277:310 Cleavage of Amyloid Precursor Protein (APP), initiated by BACE1 and followed by γ-secretase, leads to the formation of toxic Aβ peptides. 27784219 5 5 theme western 778:784 arg1 analysis 791:798 western blot analysis 778:798 western blot analysis 778:798 METHOD Detection of BACE1 secretion in BACE1 overexpressing cells or ADAM10/ADAM17 knockout fibroblasts cultured under serum deprivation conditions, using western blot analysis. 27784219 10 6 theme membrane 1468:1475 arg1 cholesterol 1477:1487 membrane cholesterol 1468:1487 membrane cholesterol 1468:1487 In support, we obtained results indicating that extraction of membrane cholesterol following incubation with methyl β cyclodextrin potentiated the effect of serum deprivation. 27784219 6 7 theme serum 823:827 arg1 deprivation 829:839 serum deprivation 823:839 serum deprivation of U251 neuroblastoma or HEK293T cells overexpressing BACE1 823:899 RESULTS We found that serum deprivation of U251 neuroblastoma or HEK293T cells overexpressing BACE1 stimulated secretion of BACE1. 27784219 1 8 theme Disease 148:154 arg1 pathogenesis 161:172 Alzheimer's Disease (AD) pathogenesis 136:172 Alzheimer's Disease (AD) pathogenesis 136:172 BACKGROUND β-secretase (BACE1) is a type 1 transmembrane protein implicated in Alzheimer's Disease (AD) pathogenesis. 27784219 6 9 theme HEK293T 866:872 arg1 cells 874:878 U251 neuroblastoma or HEK293T cells 844:878 cells 874:878 RESULTS We found that serum deprivation of U251 neuroblastoma or HEK293T cells overexpressing BACE1 stimulated secretion of BACE1. 27784219 5 10 dep overexpressing 668:681 arg1 BACE1 662:666 BACE1 662:666 BACE1 662:666 METHOD Detection of BACE1 secretion in BACE1 overexpressing cells or ADAM10/ADAM17 knockout fibroblasts cultured under serum deprivation conditions, using western blot analysis. 27784219 6 11 theme BACE1 925:929 arg1 secretion 912:920 secretion 912:920 secretion of BACE1 912:929 RESULTS We found that serum deprivation of U251 neuroblastoma or HEK293T cells overexpressing BACE1 stimulated secretion of BACE1. 27784219 2 12 theme Aβ 300:301 arg1 peptides 303:310 toxic Aβ peptides 294:310 toxic Aβ peptides 294:310 Cleavage of Amyloid Precursor Protein (APP), initiated by BACE1 and followed by γ-secretase, leads to the formation of toxic Aβ peptides. 27784219 1 13 theme BACKGROUND 57:66 arg1 protein 114:120 a type 1 transmembrane protein 91:120 a type 1 transmembrane protein implicated in Alzheimer's Disease (AD) pathogenesis 91:172 BACKGROUND β-secretase (BACE1) is a type 1 transmembrane protein implicated in Alzheimer's Disease (AD) pathogenesis. 27784219 1 13 theme BACKGROUND 57:66 arg1 BACE1 81:85 BACE1 81:85 BACE1 81:85 BACKGROUND β-secretase (BACE1) is a type 1 transmembrane protein implicated in Alzheimer's Disease (AD) pathogenesis. 27784219 1 13 theme BACKGROUND 57:66 arg1 β-secretase 68:78 BACKGROUND β-secretase 57:78 BACKGROUND β-secretase (BACE1) 57:86 BACKGROUND β-secretase (BACE1) is a type 1 transmembrane protein implicated in Alzheimer's Disease (AD) pathogenesis. 27784219 4 14 theme serum 552:556 arg1 deprivation 558:568 serum deprivation 552:568 serum deprivation 552:568 OBJECTIVE To mimic such conditions, we examined whether serum deprivation stimulates proteolysis-dependent secretion of BACE1. 27784219 3 15 theme Increased 313:321 arg1 levels 323:328 Increased levels 313:328 Increased levels of BACE1 313:337 Increased levels of BACE1 have been detected in the CSF of AD patients compared to age-matched healthy controls indicating that neurodegenerative conditions induce shedding of BACE1. 27784219 5 16 theme secretion 649:657 arg1 Detection 630:638 METHOD Detection 623:638 METHOD Detection of BACE1 secretion in BACE1 overexpressing cells or ADAM10/ADAM17 knockout fibroblasts 623:725 METHOD Detection of BACE1 secretion in BACE1 overexpressing cells or ADAM10/ADAM17 knockout fibroblasts cultured under serum deprivation conditions, using western blot analysis. 27784219 12 17 theme BACE1 1734:1738 arg1 secretion 1740:1748 ADAM10-mediated BACE1 secretion 1718:1748 ADAM10-mediated BACE1 secretion 1718:1748 CONCLUSION Serum starvation induces ADAM10-mediated BACE1 secretion. 27784219 5 18 theme serum 742:746 arg1 conditions 760:769 serum deprivation conditions 742:769 serum deprivation conditions 742:769 METHOD Detection of BACE1 secretion in BACE1 overexpressing cells or ADAM10/ADAM17 knockout fibroblasts cultured under serum deprivation conditions, using western blot analysis. 27784219 9 19 theme membrane 1343:1350 arg1 composition 1324:1334 the lipid composition 1314:1334 the lipid composition of the membrane which can alter the localization of ADAM10 and BACE1 1314:1403 We hypothesized that serum deprivation results in alterations in the lipid composition of the membrane which can alter the localization of ADAM10 and BACE1. 27784219 10 20 theme methyl 1515:1520 arg1 cyclodextrin 1524:1535 methyl β cyclodextrin 1515:1535 methyl β cyclodextrin 1515:1535 In support, we obtained results indicating that extraction of membrane cholesterol following incubation with methyl β cyclodextrin potentiated the effect of serum deprivation. 27784219 11 21 theme Secreted 1582:1589 arg1 BACE1 1591:1595 Secreted BACE1 1582:1595 Secreted BACE1 1582:1595 Secreted BACE1 was also found to be enzymatically active towards immunoprecipiated full length APP. 27784219 3 22 theme BACE1 489:493 arg1 shedding 477:484 shedding 477:484 shedding of BACE1 477:493 Increased levels of BACE1 have been detected in the CSF of AD patients compared to age-matched healthy controls indicating that neurodegenerative conditions induce shedding of BACE1. 27784219 12 23 theme ADAM10-mediated 1718:1732 arg1 secretion 1740:1748 ADAM10-mediated BACE1 secretion 1718:1748 ADAM10-mediated BACE1 secretion 1718:1748 CONCLUSION Serum starvation induces ADAM10-mediated BACE1 secretion. 27784219 3 24 theme AD 372:373 arg1 patients 375:382 AD patients 372:382 AD patients 372:382 Increased levels of BACE1 have been detected in the CSF of AD patients compared to age-matched healthy controls indicating that neurodegenerative conditions induce shedding of BACE1. 27784219 5 25 theme deprivation 748:758 arg1 conditions 760:769 serum deprivation conditions 742:769 serum deprivation conditions 742:769 METHOD Detection of BACE1 secretion in BACE1 overexpressing cells or ADAM10/ADAM17 knockout fibroblasts cultured under serum deprivation conditions, using western blot analysis. 27784219 5 26 theme BACE1 643:647 arg1 secretion 649:657 BACE1 secretion 643:657 BACE1 secretion 643:657 METHOD Detection of BACE1 secretion in BACE1 overexpressing cells or ADAM10/ADAM17 knockout fibroblasts cultured under serum deprivation conditions, using western blot analysis. 27784219 6 27 dep RESULTS 801:807 arg1 found 812:816 found 812:816 found that serum deprivation of U251 neuroblastoma or HEK293T cells overexpressing BACE1 stimulated secretion of BACE1 812:929 RESULTS We found that serum deprivation of U251 neuroblastoma or HEK293T cells overexpressing BACE1 stimulated secretion of BACE1. 27784219 3 28 theme patients 375:382 arg1 CSF 365:367 the CSF 361:367 the CSF of AD patients 361:382 Increased levels of BACE1 have been detected in the CSF of AD patients compared to age-matched healthy controls indicating that neurodegenerative conditions induce shedding of BACE1. 27784219 3 29 theme BACE1 333:337 arg1 levels 323:328 Increased levels 313:328 Increased levels of BACE1 313:337 Increased levels of BACE1 have been detected in the CSF of AD patients compared to age-matched healthy controls indicating that neurodegenerative conditions induce shedding of BACE1. 27784219 7 30 theme BACE1 1117:1121 arg1 shedding 1105:1112 serum-starvation induced shedding 1080:1112 serum-starvation induced shedding of BACE1 1080:1121 Using ADAM10/ADAM17 knockout fibroblasts and inhibitors of both ADAM10 and ADAM17, we obtained data indicating that these proteases are involved in serum-starvation induced shedding of BACE1. 27784219 0 31 theme Serum 0:4 arg1 Starvation 6:15 Serum Starvation 0:15 Serum Starvation 0:15 Serum Starvation Induces BACE1 Processing and Secretion. 27784219 4 32 theme such 515:518 arg1 conditions 520:529 such conditions 515:529 such conditions 515:529 OBJECTIVE To mimic such conditions, we examined whether serum deprivation stimulates proteolysis-dependent secretion of BACE1. 27784219 5 33 theme METHOD 623:628 arg1 Detection 630:638 METHOD Detection 623:638 METHOD Detection of BACE1 secretion in BACE1 overexpressing cells or ADAM10/ADAM17 knockout fibroblasts 623:725 METHOD Detection of BACE1 secretion in BACE1 overexpressing cells or ADAM10/ADAM17 knockout fibroblasts cultured under serum deprivation conditions, using western blot analysis. 27784219 7 34 theme knockout 952:959 arg1 fibroblasts 961:971 ADAM10/ADAM17 knockout fibroblasts 938:971 ADAM10/ADAM17 knockout fibroblasts 938:971 Using ADAM10/ADAM17 knockout fibroblasts and inhibitors of both ADAM10 and ADAM17, we obtained data indicating that these proteases are involved in serum-starvation induced shedding of BACE1. 27784219 6 35 theme neuroblastoma 849:861 arg1 deprivation 829:839 serum deprivation 823:839 serum deprivation of U251 neuroblastoma or HEK293T cells overexpressing BACE1 823:899 RESULTS We found that serum deprivation of U251 neuroblastoma or HEK293T cells overexpressing BACE1 stimulated secretion of BACE1. 27784219 10 36 with incubation 1499:1508 arg1 cyclodextrin 1524:1535 methyl β cyclodextrin 1515:1535 methyl β cyclodextrin 1515:1535 In support, we obtained results indicating that extraction of membrane cholesterol following incubation with methyl β cyclodextrin potentiated the effect of serum deprivation. 27784219 0 37 theme BACE1 25:29 arg1 Processing 31:40 BACE1 Processing 25:40 BACE1 Processing 25:40 Serum Starvation Induces BACE1 Processing and Secretion. 27784219 9 38 theme serum 1270:1274 arg1 deprivation 1276:1286 serum deprivation 1270:1286 serum deprivation 1270:1286 We hypothesized that serum deprivation results in alterations in the lipid composition of the membrane which can alter the localization of ADAM10 and BACE1. 27784219 7 39 theme ADAM10 996:1001 arg1 inhibitors 977:986 inhibitors 977:986 inhibitors of both ADAM10 and ADAM17 977:1012 Using ADAM10/ADAM17 knockout fibroblasts and inhibitors of both ADAM10 and ADAM17, we obtained data indicating that these proteases are involved in serum-starvation induced shedding of BACE1. 27784219 7 39 theme ADAM10 996:1001 arg1 fibroblasts 961:971 ADAM10/ADAM17 knockout fibroblasts 938:971 ADAM10/ADAM17 knockout fibroblasts 938:971 Using ADAM10/ADAM17 knockout fibroblasts and inhibitors of both ADAM10 and ADAM17, we obtained data indicating that these proteases are involved in serum-starvation induced shedding of BACE1. 27784219 3 40 theme age-matched 396:406 arg1 controls 416:423 age-matched healthy controls 396:423 age-matched healthy controls indicating that neurodegenerative conditions induce shedding of BACE1 396:493 Increased levels of BACE1 have been detected in the CSF of AD patients compared to age-matched healthy controls indicating that neurodegenerative conditions induce shedding of BACE1. 27784219 1 41 theme type 93:96 arg1 protein 114:120 a type 1 transmembrane protein 91:120 a type 1 transmembrane protein implicated in Alzheimer's Disease (AD) pathogenesis 91:172 BACKGROUND β-secretase (BACE1) is a type 1 transmembrane protein implicated in Alzheimer's Disease (AD) pathogenesis. 27784219 1 41 theme type 93:96 arg1 β-secretase 68:78 BACKGROUND β-secretase 57:78 BACKGROUND β-secretase (BACE1) 57:86 BACKGROUND β-secretase (BACE1) is a type 1 transmembrane protein implicated in Alzheimer's Disease (AD) pathogenesis. 27784219 3 42 theme healthy 408:414 arg1 controls 416:423 age-matched healthy controls 396:423 age-matched healthy controls indicating that neurodegenerative conditions induce shedding of BACE1 396:493 Increased levels of BACE1 have been detected in the CSF of AD patients compared to age-matched healthy controls indicating that neurodegenerative conditions induce shedding of BACE1. 27784219 5 43 theme blot 786:789 arg1 analysis 791:798 western blot analysis 778:798 western blot analysis 778:798 METHOD Detection of BACE1 secretion in BACE1 overexpressing cells or ADAM10/ADAM17 knockout fibroblasts cultured under serum deprivation conditions, using western blot analysis. 27784219 3 44 theme neurodegenerative 441:457 arg1 conditions 459:468 neurodegenerative conditions 441:468 neurodegenerative conditions 441:468 Increased levels of BACE1 have been detected in the CSF of AD patients compared to age-matched healthy controls indicating that neurodegenerative conditions induce shedding of BACE1. 27784219 5 45 theme knockout 706:713 arg1 fibroblasts 715:725 ADAM10/ADAM17 knockout fibroblasts 692:725 ADAM10/ADAM17 knockout fibroblasts 692:725 METHOD Detection of BACE1 secretion in BACE1 overexpressing cells or ADAM10/ADAM17 knockout fibroblasts cultured under serum deprivation conditions, using western blot analysis. 27784219 6 46 theme cells 874:878 arg1 deprivation 829:839 serum deprivation 823:839 serum deprivation of U251 neuroblastoma or HEK293T cells overexpressing BACE1 823:899 RESULTS We found that serum deprivation of U251 neuroblastoma or HEK293T cells overexpressing BACE1 stimulated secretion of BACE1. 27784219 8 47 located localized 1206:1214 arg1 domains 1240:1246 nonlipid raft domains 1226:1246 nonlipid raft domains 1226:1246 This is unexpected since BACE1 is localized mainly in lipid rafts while ADAM10 is localized mainly in nonlipid raft domains. 27784219 8 47 located localized 1206:1214 arg2 ADAM10 1196:1201 ADAM10 1196:1201 ADAM10 1196:1201 This is unexpected since BACE1 is localized mainly in lipid rafts while ADAM10 is localized mainly in nonlipid raft domains. 27784219 8 48 theme raft 1235:1238 arg1 domains 1240:1246 nonlipid raft domains 1226:1246 nonlipid raft domains 1226:1246 This is unexpected since BACE1 is localized mainly in lipid rafts while ADAM10 is localized mainly in nonlipid raft domains. 27784219 9 49 theme ADAM10 1388:1393 arg1 localization 1372:1383 the localization 1368:1383 the localization of ADAM10 and BACE1 1368:1403 We hypothesized that serum deprivation results in alterations in the lipid composition of the membrane which can alter the localization of ADAM10 and BACE1. 27784219 7 50 theme induced 1097:1103 arg1 shedding 1105:1112 serum-starvation induced shedding 1080:1112 serum-starvation induced shedding of BACE1 1080:1121 Using ADAM10/ADAM17 knockout fibroblasts and inhibitors of both ADAM10 and ADAM17, we obtained data indicating that these proteases are involved in serum-starvation induced shedding of BACE1. 27784219 3 51 located detected 349:356 arg2 levels 323:328 Increased levels 313:328 Increased levels of BACE1 313:337 Increased levels of BACE1 have been detected in the CSF of AD patients compared to age-matched healthy controls indicating that neurodegenerative conditions induce shedding of BACE1. 27784219 3 51 located detected 349:356 arg1 CSF 365:367 the CSF 361:367 the CSF of AD patients 361:382 Increased levels of BACE1 have been detected in the CSF of AD patients compared to age-matched healthy controls indicating that neurodegenerative conditions induce shedding of BACE1. 27784219 8 52 theme nonlipid 1226:1233 arg1 domains 1240:1246 nonlipid raft domains 1226:1246 nonlipid raft domains 1226:1246 This is unexpected since BACE1 is localized mainly in lipid rafts while ADAM10 is localized mainly in nonlipid raft domains. 27784219 10 53 theme deprivation 1569:1579 arg1 effect 1553:1558 the effect 1549:1558 the effect of serum deprivation 1549:1579 In support, we obtained results indicating that extraction of membrane cholesterol following incubation with methyl β cyclodextrin potentiated the effect of serum deprivation. 27784219 2 54 theme Protein 205:211 arg1 Cleavage 175:182 Cleavage 175:182 Cleavage 175:182 Cleavage of Amyloid Precursor Protein (APP), initiated by BACE1 and followed by γ-secretase, leads to the formation of toxic Aβ peptides. 27784219 11 55 theme immunoprecipiated 1647:1663 arg1 APP 1677:1679 immunoprecipiated full length APP 1647:1679 immunoprecipiated full length APP 1647:1679 Secreted BACE1 was also found to be enzymatically active towards immunoprecipiated full length APP. 27784219 2 56 theme toxic 294:298 arg1 peptides 303:310 toxic Aβ peptides 294:310 toxic Aβ peptides 294:310 Cleavage of Amyloid Precursor Protein (APP), initiated by BACE1 and followed by γ-secretase, leads to the formation of toxic Aβ peptides. 27784219 10 57 theme β 1522:1522 arg1 cyclodextrin 1524:1535 methyl β cyclodextrin 1515:1535 methyl β cyclodextrin 1515:1535 In support, we obtained results indicating that extraction of membrane cholesterol following incubation with methyl β cyclodextrin potentiated the effect of serum deprivation. 27784219 5 58 from Detection 630:638 arg1 cells 683:687 BACE1 overexpressing cells 662:687 BACE1 overexpressing cells 662:687 METHOD Detection of BACE1 secretion in BACE1 overexpressing cells or ADAM10/ADAM17 knockout fibroblasts cultured under serum deprivation conditions, using western blot analysis. 27784219 5 58 from Detection 630:638 arg1 fibroblasts 715:725 ADAM10/ADAM17 knockout fibroblasts 692:725 ADAM10/ADAM17 knockout fibroblasts 692:725 METHOD Detection of BACE1 secretion in BACE1 overexpressing cells or ADAM10/ADAM17 knockout fibroblasts cultured under serum deprivation conditions, using western blot analysis. 27784219 10 59 theme serum 1563:1567 arg1 deprivation 1569:1579 serum deprivation 1563:1579 serum deprivation 1563:1579 In support, we obtained results indicating that extraction of membrane cholesterol following incubation with methyl β cyclodextrin potentiated the effect of serum deprivation. 27784219 2 60 theme Amyloid 187:193 arg1 APP 214:216 APP 214:216 APP 214:216 Cleavage of Amyloid Precursor Protein (APP), initiated by BACE1 and followed by γ-secretase, leads to the formation of toxic Aβ peptides. 27784219 2 60 theme Amyloid 187:193 arg1 Protein 205:211 Amyloid Precursor Protein 187:211 Amyloid Precursor Protein (APP) 187:217 Cleavage of Amyloid Precursor Protein (APP), initiated by BACE1 and followed by γ-secretase, leads to the formation of toxic Aβ peptides. 27784219 2 61 theme Precursor 195:203 arg1 APP 214:216 APP 214:216 APP 214:216 Cleavage of Amyloid Precursor Protein (APP), initiated by BACE1 and followed by γ-secretase, leads to the formation of toxic Aβ peptides. 27784219 2 61 theme Precursor 195:203 arg1 Protein 205:211 Amyloid Precursor Protein 187:211 Amyloid Precursor Protein (APP) 187:217 Cleavage of Amyloid Precursor Protein (APP), initiated by BACE1 and followed by γ-secretase, leads to the formation of toxic Aβ peptides. 27784219 1 62 theme transmembrane 100:112 arg1 protein 114:120 a type 1 transmembrane protein 91:120 a type 1 transmembrane protein implicated in Alzheimer's Disease (AD) pathogenesis 91:172 BACKGROUND β-secretase (BACE1) is a type 1 transmembrane protein implicated in Alzheimer's Disease (AD) pathogenesis. 27784219 1 62 theme transmembrane 100:112 arg1 β-secretase 68:78 BACKGROUND β-secretase 57:78 BACKGROUND β-secretase (BACE1) 57:86 BACKGROUND β-secretase (BACE1) is a type 1 transmembrane protein implicated in Alzheimer's Disease (AD) pathogenesis. 27784219 5 63 theme overexpressing 668:681 arg1 cells 683:687 BACE1 overexpressing cells 662:687 BACE1 overexpressing cells 662:687 METHOD Detection of BACE1 secretion in BACE1 overexpressing cells or ADAM10/ADAM17 knockout fibroblasts cultured under serum deprivation conditions, using western blot analysis. 27784219 6 64 theme U251 844:847 arg1 neuroblastoma 849:861 U251 neuroblastoma or HEK293T cells 844:878 neuroblastoma 849:861 RESULTS We found that serum deprivation of U251 neuroblastoma or HEK293T cells overexpressing BACE1 stimulated secretion of BACE1. 27784219 11 65 theme full 1665:1668 arg1 APP 1677:1679 immunoprecipiated full length APP 1647:1679 immunoprecipiated full length APP 1647:1679 Secreted BACE1 was also found to be enzymatically active towards immunoprecipiated full length APP. 27784219 2 66 dep Cleavage 175:182 arg1 followed 243:250 followed 243:250 followed by γ-secretase 243:265 Cleavage of Amyloid Precursor Protein (APP), initiated by BACE1 and followed by γ-secretase, leads to the formation of toxic Aβ peptides. 27784219 2 66 dep Cleavage 175:182 arg1 initiated 220:228 initiated 220:228 initiated by BACE1 220:237 Cleavage of Amyloid Precursor Protein (APP), initiated by BACE1 and followed by γ-secretase, leads to the formation of toxic Aβ peptides. 27784219 8 67 located localized 1158:1166 arg2 BACE1 1149:1153 BACE1 1149:1153 BACE1 1149:1153 This is unexpected since BACE1 is localized mainly in lipid rafts while ADAM10 is localized mainly in nonlipid raft domains. 27784219 8 67 located localized 1158:1166 arg1 rafts 1184:1188 lipid rafts 1178:1188 lipid rafts 1178:1188 This is unexpected since BACE1 is localized mainly in lipid rafts while ADAM10 is localized mainly in nonlipid raft domains. 27784219 12 68 theme CONCLUSION 1682:1691 arg1 starvation 1699:1708 CONCLUSION Serum starvation 1682:1708 CONCLUSION Serum starvation 1682:1708 CONCLUSION Serum starvation induces ADAM10-mediated BACE1 secretion. 27784219 9 69 from alterations 1299:1309 arg1 composition 1324:1334 the lipid composition 1314:1334 the lipid composition of the membrane which can alter the localization of ADAM10 and BACE1 1314:1403 We hypothesized that serum deprivation results in alterations in the lipid composition of the membrane which can alter the localization of ADAM10 and BACE1. 27784219 9 70 theme BACE1 1399:1403 arg1 localization 1372:1383 the localization 1368:1383 the localization of ADAM10 and BACE1 1368:1403 We hypothesized that serum deprivation results in alterations in the lipid composition of the membrane which can alter the localization of ADAM10 and BACE1. 27784219 4 71 theme BACE1 616:620 arg1 secretion 603:611 proteolysis-dependent secretion 581:611 proteolysis-dependent secretion of BACE1 581:620 OBJECTIVE To mimic such conditions, we examined whether serum deprivation stimulates proteolysis-dependent secretion of BACE1. 27784219 7 72 theme ADAM17 1007:1012 arg1 inhibitors 977:986 inhibitors 977:986 inhibitors of both ADAM10 and ADAM17 977:1012 Using ADAM10/ADAM17 knockout fibroblasts and inhibitors of both ADAM10 and ADAM17, we obtained data indicating that these proteases are involved in serum-starvation induced shedding of BACE1. 27784219 7 72 theme ADAM17 1007:1012 arg1 fibroblasts 961:971 ADAM10/ADAM17 knockout fibroblasts 938:971 ADAM10/ADAM17 knockout fibroblasts 938:971 Using ADAM10/ADAM17 knockout fibroblasts and inhibitors of both ADAM10 and ADAM17, we obtained data indicating that these proteases are involved in serum-starvation induced shedding of BACE1. 27784219 12 73 theme Serum 1693:1697 arg1 starvation 1699:1708 CONCLUSION Serum starvation 1682:1708 CONCLUSION Serum starvation 1682:1708 CONCLUSION Serum starvation induces ADAM10-mediated BACE1 secretion. 27784219 4 74 theme proteolysis-dependent 581:601 arg1 secretion 603:611 proteolysis-dependent secretion 581:611 proteolysis-dependent secretion of BACE1 581:620 OBJECTIVE To mimic such conditions, we examined whether serum deprivation stimulates proteolysis-dependent secretion of BACE1. 28389847 4 0 theme GlycoWorkbench 771:784 arg1 program 786:792 the GlycoWorkbench program 767:792 the GlycoWorkbench program 767:792 Representative MS spectra of N-glycans with signal-to-noise ratios >6 were annotated using the GlycoWorkbench program. 28389847 9 1 theme biomarkers 1752:1761 arg1 discovery 1739:1747 the discovery 1735:1747 the discovery of biomarkers for HCC during its early stages based on precise alterations of N-linked glycans 1735:1842 Our data provide pivotal information to distinguish between HBV-associated hepatitis, cirrhosis and HCC, and facilitate the discovery of biomarkers for HCC during its early stages based on precise alterations of N-linked glycans in saliva. 28389847 1 2 from risk 275:278 arg1 cirrhosis 294:302 cirrhosis 294:302 cirrhosis of the liver and liver cancer 294:332 Hepatitis B is a potentially life-threatening liver infection caused by the hepatitis B virus (HBV), which can lead to chronic liver disease and put people at high risk of death from cirrhosis of the liver and liver cancer. 28389847 7 3 from group 1267:1271 arg1 unique 1254:1259 unique 1254:1259 unique 1254:1259 Three N-glycan peaks (m/z 2596.925, 2756.962, and 2921.031) were unique in HV group, 2 N-glycan peaks (m/z 1898.676 and 1971.692) were unique in HB group, 5 N-glycan peaks (m/z 1954.677, 2507.914, 2580.930, 2637.952, and 3092.120) were unique in HC group, and 3 N-glycan peaks (m/z 2240.830, 2507.914, and 3931.338) were unique in HCC group. 28389847 6 4 located present 995:1001 arg2 peaks 940:944 15 N-glycan peaks 928:944 15 N-glycan peaks (e.g., m/z 1647.587, 1688.613 and 2101.755) were present in all groups 928:1015 There were 15 N-glycan peaks (e.g., m/z 1647.587, 1688.613 and 2101.755) were present in all groups. 28389847 6 4 located present 995:1001 arg1 groups 1010:1015 all groups 1006:1015 all groups 1006:1015 There were 15 N-glycan peaks (e.g., m/z 1647.587, 1688.613 and 2101.755) were present in all groups. 28389847 3 5 from patients 562:569 arg1 glycome 481:487 N-linked glycome 472:487 N-linked glycome in saliva from 200 subjects (50 healthy volunteers (HV), 40 HBV-infected patients (HB), 50 cirrhosis patients (HC), and 60 hepatocellular carcinoma patients (HCC) 472:650 Here we investigated N-linked glycome in saliva from 200 subjects (50 healthy volunteers (HV), 40 HBV-infected patients (HB), 50 cirrhosis patients (HC), and 60 hepatocellular carcinoma patients (HCC) using MALDI-TOF/TOF-MS. 28389847 1 6 theme chronic 230:236 arg1 disease 244:250 chronic liver disease 230:250 chronic liver disease 230:250 Hepatitis B is a potentially life-threatening liver infection caused by the hepatitis B virus (HBV), which can lead to chronic liver disease and put people at high risk of death from cirrhosis of the liver and liver cancer. 28389847 7 7 theme m/z 1191:1193 arg1 1954.677 1195:1202 m/z 1954.677 1191:1202 m/z 1954.677 1191:1202 Three N-glycan peaks (m/z 2596.925, 2756.962, and 2921.031) were unique in HV group, 2 N-glycan peaks (m/z 1898.676 and 1971.692) were unique in HB group, 5 N-glycan peaks (m/z 1954.677, 2507.914, 2580.930, 2637.952, and 3092.120) were unique in HC group, and 3 N-glycan peaks (m/z 2240.830, 2507.914, and 3931.338) were unique in HCC group. 28389847 8 8 theme sialylated 1517:1526 arg1 N-glycans 1528:1536 sialylated N-glycans 1517:1536 sialylated N-glycans 1517:1536 The proportion of fucosylated N-glycans was apparently increased in the HCC group (84.8%) than in any other group (73.1% ± 0.01), however, the proportion of sialylated N-glycans was decreased in HCC group (12.1%) than in any other group (17.23% ± 0.003). 28389847 3 9 theme carcinoma 627:635 arg1 HCC 647:649 HCC 647:649 HCC 647:649 Here we investigated N-linked glycome in saliva from 200 subjects (50 healthy volunteers (HV), 40 HBV-infected patients (HB), 50 cirrhosis patients (HC), and 60 hepatocellular carcinoma patients (HCC) using MALDI-TOF/TOF-MS. 28389847 3 9 theme carcinoma 627:635 arg1 patients 637:644 60 hepatocellular carcinoma patients 609:644 60 hepatocellular carcinoma patients (HCC) 609:650 Here we investigated N-linked glycome in saliva from 200 subjects (50 healthy volunteers (HV), 40 HBV-infected patients (HB), 50 cirrhosis patients (HC), and 60 hepatocellular carcinoma patients (HCC) using MALDI-TOF/TOF-MS. 28389847 1 10 theme liver 321:325 arg1 cancer 327:332 liver cancer 321:332 liver cancer 321:332 Hepatitis B is a potentially life-threatening liver infection caused by the hepatitis B virus (HBV), which can lead to chronic liver disease and put people at high risk of death from cirrhosis of the liver and liver cancer. 28389847 1 11 theme B 197:197 arg1 HBV 206:208 HBV 206:208 HBV 206:208 Hepatitis B is a potentially life-threatening liver infection caused by the hepatitis B virus (HBV), which can lead to chronic liver disease and put people at high risk of death from cirrhosis of the liver and liver cancer. 28389847 1 11 theme B 197:197 arg1 virus 199:203 the hepatitis B virus 183:203 the hepatitis B virus (HBV) 183:209 Hepatitis B is a potentially life-threatening liver infection caused by the hepatitis B virus (HBV), which can lead to chronic liver disease and put people at high risk of death from cirrhosis of the liver and liver cancer. 28389847 7 12 theme HCC 1349:1351 arg1 group 1353:1357 HCC group 1349:1357 HCC group 1349:1357 Three N-glycan peaks (m/z 2596.925, 2756.962, and 2921.031) were unique in HV group, 2 N-glycan peaks (m/z 1898.676 and 1971.692) were unique in HB group, 5 N-glycan peaks (m/z 1954.677, 2507.914, 2580.930, 2637.952, and 3092.120) were unique in HC group, and 3 N-glycan peaks (m/z 2240.830, 2507.914, and 3931.338) were unique in HCC group. 28389847 7 13 theme HB 1163:1164 arg1 group 1166:1170 HB group 1163:1170 HB group 1163:1170 Three N-glycan peaks (m/z 2596.925, 2756.962, and 2921.031) were unique in HV group, 2 N-glycan peaks (m/z 1898.676 and 1971.692) were unique in HB group, 5 N-glycan peaks (m/z 1954.677, 2507.914, 2580.930, 2637.952, and 3092.120) were unique in HC group, and 3 N-glycan peaks (m/z 2240.830, 2507.914, and 3931.338) were unique in HCC group. 28389847 9 14 link N-linked 1827:1834 arg1 glycans 1836:1842 N-linked glycans 1827:1842 N-linked glycans 1827:1842 Our data provide pivotal information to distinguish between HBV-associated hepatitis, cirrhosis and HCC, and facilitate the discovery of biomarkers for HCC during its early stages based on precise alterations of N-linked glycans in saliva. 28389847 9 15 theme N-linked 1827:1834 arg1 glycans 1836:1842 N-linked glycans 1827:1842 N-linked glycans 1827:1842 Our data provide pivotal information to distinguish between HBV-associated hepatitis, cirrhosis and HCC, and facilitate the discovery of biomarkers for HCC during its early stages based on precise alterations of N-linked glycans in saliva. 28389847 5 16 theme HCC 891:893 arg1 groups 895:900 HCC groups 891:900 HCC groups 891:900 A total of 40, 47, 29, and 33 N-glycan peaks were identified and annotated from HV, HB, HC, and HCC groups, respectively. 28389847 3 17 theme healthy 521:527 arg1 volunteers 529:538 50 healthy volunteers 518:538 50 healthy volunteers (HV) 518:543 Here we investigated N-linked glycome in saliva from 200 subjects (50 healthy volunteers (HV), 40 HBV-infected patients (HB), 50 cirrhosis patients (HC), and 60 hepatocellular carcinoma patients (HCC) using MALDI-TOF/TOF-MS. 28389847 3 17 theme healthy 521:527 arg1 HV 541:542 HV 541:542 HV 541:542 Here we investigated N-linked glycome in saliva from 200 subjects (50 healthy volunteers (HV), 40 HBV-infected patients (HB), 50 cirrhosis patients (HC), and 60 hepatocellular carcinoma patients (HCC) using MALDI-TOF/TOF-MS. 28389847 8 18 theme other 1462:1466 arg1 group 1468:1472 any other group 1458:1472 any other group 1458:1472 The proportion of fucosylated N-glycans was apparently increased in the HCC group (84.8%) than in any other group (73.1% ± 0.01), however, the proportion of sialylated N-glycans was decreased in HCC group (12.1%) than in any other group (17.23% ± 0.003). 28389847 5 19 theme 47 810:811 arg1 total 797:801 A total 795:801 A total of 40, 47, 29, and 33 N-glycan peaks 795:838 A total of 40, 47, 29, and 33 N-glycan peaks were identified and annotated from HV, HB, HC, and HCC groups, respectively. 28389847 8 20 theme other 1585:1589 arg1 % 1603:1603 17.23% ± 0.003 1598:1611 17.23% ± 0.003 1598:1611 The proportion of fucosylated N-glycans was apparently increased in the HCC group (84.8%) than in any other group (73.1% ± 0.01), however, the proportion of sialylated N-glycans was decreased in HCC group (12.1%) than in any other group (17.23% ± 0.003). 28389847 8 20 theme other 1585:1589 arg1 group 1591:1595 any other group 1581:1595 any other group (17.23% ± 0.003) 1581:1612 The proportion of fucosylated N-glycans was apparently increased in the HCC group (84.8%) than in any other group (73.1% ± 0.01), however, the proportion of sialylated N-glycans was decreased in HCC group (12.1%) than in any other group (17.23% ± 0.003). 28389847 5 21 theme 29 814:815 arg1 total 797:801 A total 795:801 A total of 40, 47, 29, and 33 N-glycan peaks 795:838 A total of 40, 47, 29, and 33 N-glycan peaks were identified and annotated from HV, HB, HC, and HCC groups, respectively. 28389847 0 22 theme chronic 51:57 arg1 hepatitis 59:67 HBV-induced chronic hepatitis 39:67 HBV-induced chronic hepatitis 39:67 A pilot study of salivary N-glycome in HBV-induced chronic hepatitis, cirrhosis, and hepatocellular carcinoma. 28389847 2 23 theme HBV-infected 422:433 arg1 diseases 441:448 HBV-infected liver diseases 422:448 HBV-infected liver diseases 422:448 However, little is known about the correlation of salivary N-linked glycans related to HBV-infected liver diseases. 28389847 0 24 from study 8:12 arg1 cirrhosis 70:78 cirrhosis 70:78 cirrhosis 70:78 A pilot study of salivary N-glycome in HBV-induced chronic hepatitis, cirrhosis, and hepatocellular carcinoma. 28389847 0 24 from study 8:12 arg1 hepatitis 59:67 HBV-induced chronic hepatitis 39:67 HBV-induced chronic hepatitis 39:67 A pilot study of salivary N-glycome in HBV-induced chronic hepatitis, cirrhosis, and hepatocellular carcinoma. 28389847 0 24 from study 8:12 arg1 carcinoma 100:108 hepatocellular carcinoma 85:108 hepatocellular carcinoma 85:108 A pilot study of salivary N-glycome in HBV-induced chronic hepatitis, cirrhosis, and hepatocellular carcinoma. 28389847 3 25 from glycome 481:487 arg1 saliva 492:497 saliva 492:497 saliva 492:497 Here we investigated N-linked glycome in saliva from 200 subjects (50 healthy volunteers (HV), 40 HBV-infected patients (HB), 50 cirrhosis patients (HC), and 60 hepatocellular carcinoma patients (HCC) using MALDI-TOF/TOF-MS. 28389847 1 26 theme liver 157:161 arg1 B 121:121 Hepatitis B 111:121 Hepatitis B 111:121 Hepatitis B is a potentially life-threatening liver infection caused by the hepatitis B virus (HBV), which can lead to chronic liver disease and put people at high risk of death from cirrhosis of the liver and liver cancer. 28389847 1 26 theme liver 157:161 arg1 infection 163:171 a potentially life-threatening liver infection 126:171 a potentially life-threatening liver infection caused by the hepatitis B virus (HBV), which can lead to chronic liver disease and put people at high risk of death from cirrhosis of the liver and liver cancer 126:332 Hepatitis B is a potentially life-threatening liver infection caused by the hepatitis B virus (HBV), which can lead to chronic liver disease and put people at high risk of death from cirrhosis of the liver and liver cancer. 28389847 3 27 link N-linked 472:479 arg1 glycome 481:487 N-linked glycome 472:487 N-linked glycome in saliva from 200 subjects (50 healthy volunteers (HV), 40 HBV-infected patients (HB), 50 cirrhosis patients (HC), and 60 hepatocellular carcinoma patients (HCC) 472:650 Here we investigated N-linked glycome in saliva from 200 subjects (50 healthy volunteers (HV), 40 HBV-infected patients (HB), 50 cirrhosis patients (HC), and 60 hepatocellular carcinoma patients (HCC) using MALDI-TOF/TOF-MS. 28389847 9 28 theme pivotal 1632:1638 arg1 information 1640:1650 pivotal information to distinguish between HBV-associated hepatitis, cirrhosis and HCC, and facilitate the discovery of biomarkers for HCC during its early stages based on precise alterations of N-linked glycans in saliva 1632:1852 pivotal information to distinguish between HBV-associated hepatitis, cirrhosis and HCC, and facilitate the discovery of biomarkers for HCC during its early stages based on precise alterations of N-linked glycans in saliva 1632:1852 Our data provide pivotal information to distinguish between HBV-associated hepatitis, cirrhosis and HCC, and facilitate the discovery of biomarkers for HCC during its early stages based on precise alterations of N-linked glycans in saliva. 28389847 7 29 from unique 1339:1344 arg1 group 1353:1357 HCC group 1349:1357 HCC group 1349:1357 Three N-glycan peaks (m/z 2596.925, 2756.962, and 2921.031) were unique in HV group, 2 N-glycan peaks (m/z 1898.676 and 1971.692) were unique in HB group, 5 N-glycan peaks (m/z 1954.677, 2507.914, 2580.930, 2637.952, and 3092.120) were unique in HC group, and 3 N-glycan peaks (m/z 2240.830, 2507.914, and 3931.338) were unique in HCC group. 28389847 6 30 from present 995:1001 arg1 groups 1010:1015 all groups 1006:1015 all groups 1006:1015 There were 15 N-glycan peaks (e.g., m/z 1647.587, 1688.613 and 2101.755) were present in all groups. 28389847 0 31 theme hepatocellular 85:98 arg1 carcinoma 100:108 hepatocellular carcinoma 85:108 hepatocellular carcinoma 85:108 A pilot study of salivary N-glycome in HBV-induced chronic hepatitis, cirrhosis, and hepatocellular carcinoma. 28389847 1 32 theme liver 311:315 arg1 cirrhosis 294:302 cirrhosis 294:302 cirrhosis of the liver and liver cancer 294:332 Hepatitis B is a potentially life-threatening liver infection caused by the hepatitis B virus (HBV), which can lead to chronic liver disease and put people at high risk of death from cirrhosis of the liver and liver cancer. 28389847 1 33 theme liver 238:242 arg1 disease 244:250 chronic liver disease 230:250 chronic liver disease 230:250 Hepatitis B is a potentially life-threatening liver infection caused by the hepatitis B virus (HBV), which can lead to chronic liver disease and put people at high risk of death from cirrhosis of the liver and liver cancer. 28389847 7 34 from unique 1153:1158 arg1 group 1166:1170 HB group 1163:1170 HB group 1163:1170 Three N-glycan peaks (m/z 2596.925, 2756.962, and 2921.031) were unique in HV group, 2 N-glycan peaks (m/z 1898.676 and 1971.692) were unique in HB group, 5 N-glycan peaks (m/z 1954.677, 2507.914, 2580.930, 2637.952, and 3092.120) were unique in HC group, and 3 N-glycan peaks (m/z 2240.830, 2507.914, and 3931.338) were unique in HCC group. 28389847 5 35 theme peaks 834:838 arg1 total 797:801 A total 795:801 A total of 40, 47, 29, and 33 N-glycan peaks 795:838 A total of 40, 47, 29, and 33 N-glycan peaks were identified and annotated from HV, HB, HC, and HCC groups, respectively. 28389847 7 36 theme 2 N-glycan 1103:1112 arg1 m/z 1121:1123 m/z 1898.676 and 1971.692 1121:1145 m/z 1121:1123 Three N-glycan peaks (m/z 2596.925, 2756.962, and 2921.031) were unique in HV group, 2 N-glycan peaks (m/z 1898.676 and 1971.692) were unique in HB group, 5 N-glycan peaks (m/z 1954.677, 2507.914, 2580.930, 2637.952, and 3092.120) were unique in HC group, and 3 N-glycan peaks (m/z 2240.830, 2507.914, and 3931.338) were unique in HCC group. 28389847 7 36 theme 2 N-glycan 1103:1112 arg1 1971.692 1138:1145 1971.692 1138:1145 1971.692 1138:1145 Three N-glycan peaks (m/z 2596.925, 2756.962, and 2921.031) were unique in HV group, 2 N-glycan peaks (m/z 1898.676 and 1971.692) were unique in HB group, 5 N-glycan peaks (m/z 1954.677, 2507.914, 2580.930, 2637.952, and 3092.120) were unique in HC group, and 3 N-glycan peaks (m/z 2240.830, 2507.914, and 3931.338) were unique in HCC group. 28389847 7 36 theme 2 N-glycan 1103:1112 arg1 peaks 1114:1118 2 N-glycan peaks 1103:1118 2 N-glycan peaks (m/z 1898.676 and 1971.692) 1103:1146 Three N-glycan peaks (m/z 2596.925, 2756.962, and 2921.031) were unique in HV group, 2 N-glycan peaks (m/z 1898.676 and 1971.692) were unique in HB group, 5 N-glycan peaks (m/z 1954.677, 2507.914, 2580.930, 2637.952, and 3092.120) were unique in HC group, and 3 N-glycan peaks (m/z 2240.830, 2507.914, and 3931.338) were unique in HCC group. 28389847 2 37 theme related 411:417 arg1 glycans 403:409 salivary N-linked glycans 385:409 salivary N-linked glycans related to HBV-infected liver diseases 385:448 However, little is known about the correlation of salivary N-linked glycans related to HBV-infected liver diseases. 28389847 0 38 theme salivary 17:24 arg1 N-glycome 26:34 salivary N-glycome 17:34 salivary N-glycome 17:34 A pilot study of salivary N-glycome in HBV-induced chronic hepatitis, cirrhosis, and hepatocellular carcinoma. 28389847 1 39 from cirrhosis 294:302 arg1 death 283:287 death 283:287 death from cirrhosis of the liver and liver cancer 283:332 Hepatitis B is a potentially life-threatening liver infection caused by the hepatitis B virus (HBV), which can lead to chronic liver disease and put people at high risk of death from cirrhosis of the liver and liver cancer. 28389847 1 39 from cirrhosis 294:302 arg1 risk 275:278 high risk 270:278 high risk of death from cirrhosis of the liver and liver cancer 270:332 Hepatitis B is a potentially life-threatening liver infection caused by the hepatitis B virus (HBV), which can lead to chronic liver disease and put people at high risk of death from cirrhosis of the liver and liver cancer. 28389847 2 40 theme N-linked 394:401 arg1 glycans 403:409 salivary N-linked glycans 385:409 salivary N-linked glycans related to HBV-infected liver diseases 385:448 However, little is known about the correlation of salivary N-linked glycans related to HBV-infected liver diseases. 28389847 1 41 theme high 270:273 arg1 risk 275:278 high risk 270:278 high risk of death from cirrhosis of the liver and liver cancer 270:332 Hepatitis B is a potentially life-threatening liver infection caused by the hepatitis B virus (HBV), which can lead to chronic liver disease and put people at high risk of death from cirrhosis of the liver and liver cancer. 28389847 8 42 gly sialylated 1517:1526 arg1 N-glycans 1528:1536 sialylated N-glycans 1517:1536 sialylated N-glycans 1517:1536 The proportion of fucosylated N-glycans was apparently increased in the HCC group (84.8%) than in any other group (73.1% ± 0.01), however, the proportion of sialylated N-glycans was decreased in HCC group (12.1%) than in any other group (17.23% ± 0.003). 28389847 3 43 theme cirrhosis 580:588 arg1 HC 600:601 HC 600:601 HC 600:601 Here we investigated N-linked glycome in saliva from 200 subjects (50 healthy volunteers (HV), 40 HBV-infected patients (HB), 50 cirrhosis patients (HC), and 60 hepatocellular carcinoma patients (HCC) using MALDI-TOF/TOF-MS. 28389847 3 43 theme cirrhosis 580:588 arg1 patients 590:597 50 cirrhosis patients 577:597 50 cirrhosis patients (HC) 577:602 Here we investigated N-linked glycome in saliva from 200 subjects (50 healthy volunteers (HV), 40 HBV-infected patients (HB), 50 cirrhosis patients (HC), and 60 hepatocellular carcinoma patients (HCC) using MALDI-TOF/TOF-MS. 28389847 4 44 theme MS 691:692 arg1 spectra 694:700 Representative MS spectra 676:700 Representative MS spectra of N-glycans with signal-to-noise ratios >6 676:744 Representative MS spectra of N-glycans with signal-to-noise ratios >6 were annotated using the GlycoWorkbench program. 28389847 6 45 dep peaks 940:944 arg1 2101.755 980:987 2101.755 980:987 2101.755 980:987 There were 15 N-glycan peaks (e.g., m/z 1647.587, 1688.613 and 2101.755) were present in all groups. 28389847 6 45 dep peaks 940:944 arg1 1688.613 967:974 1688.613 967:974 1688.613 967:974 There were 15 N-glycan peaks (e.g., m/z 1647.587, 1688.613 and 2101.755) were present in all groups. 28389847 7 46 from unique 1254:1259 arg1 group 1267:1271 HC group 1264:1271 HC group 1264:1271 Three N-glycan peaks (m/z 2596.925, 2756.962, and 2921.031) were unique in HV group, 2 N-glycan peaks (m/z 1898.676 and 1971.692) were unique in HB group, 5 N-glycan peaks (m/z 1954.677, 2507.914, 2580.930, 2637.952, and 3092.120) were unique in HC group, and 3 N-glycan peaks (m/z 2240.830, 2507.914, and 3931.338) were unique in HCC group. 28389847 8 47 theme N-glycans 1528:1536 arg1 proportion 1503:1512 the proportion 1499:1512 the proportion of sialylated N-glycans 1499:1536 The proportion of fucosylated N-glycans was apparently increased in the HCC group (84.8%) than in any other group (73.1% ± 0.01), however, the proportion of sialylated N-glycans was decreased in HCC group (12.1%) than in any other group (17.23% ± 0.003). 28389847 8 48 theme N-glycans 1390:1398 arg1 proportion 1364:1373 The proportion 1360:1373 The proportion of fucosylated N-glycans 1360:1398 The proportion of fucosylated N-glycans was apparently increased in the HCC group (84.8%) than in any other group (73.1% ± 0.01), however, the proportion of sialylated N-glycans was decreased in HCC group (12.1%) than in any other group (17.23% ± 0.003). 28389847 8 49 gly fucosylated 1378:1388 arg1 N-glycans 1390:1398 fucosylated N-glycans 1378:1398 fucosylated N-glycans 1378:1398 The proportion of fucosylated N-glycans was apparently increased in the HCC group (84.8%) than in any other group (73.1% ± 0.01), however, the proportion of sialylated N-glycans was decreased in HCC group (12.1%) than in any other group (17.23% ± 0.003). 28389847 7 50 dep peaks 1184:1188 arg1 1954.677 1195:1202 m/z 1954.677 1191:1202 m/z 1954.677 1191:1202 Three N-glycan peaks (m/z 2596.925, 2756.962, and 2921.031) were unique in HV group, 2 N-glycan peaks (m/z 1898.676 and 1971.692) were unique in HB group, 5 N-glycan peaks (m/z 1954.677, 2507.914, 2580.930, 2637.952, and 3092.120) were unique in HC group, and 3 N-glycan peaks (m/z 2240.830, 2507.914, and 3931.338) were unique in HCC group. 28389847 7 50 dep peaks 1184:1188 arg1 2637.952 1225:1232 2637.952 1225:1232 2637.952 1225:1232 Three N-glycan peaks (m/z 2596.925, 2756.962, and 2921.031) were unique in HV group, 2 N-glycan peaks (m/z 1898.676 and 1971.692) were unique in HB group, 5 N-glycan peaks (m/z 1954.677, 2507.914, 2580.930, 2637.952, and 3092.120) were unique in HC group, and 3 N-glycan peaks (m/z 2240.830, 2507.914, and 3931.338) were unique in HCC group. 28389847 7 50 dep peaks 1184:1188 arg1 3092.120 1239:1246 3092.120 1239:1246 3092.120 1239:1246 Three N-glycan peaks (m/z 2596.925, 2756.962, and 2921.031) were unique in HV group, 2 N-glycan peaks (m/z 1898.676 and 1971.692) were unique in HB group, 5 N-glycan peaks (m/z 1954.677, 2507.914, 2580.930, 2637.952, and 3092.120) were unique in HC group, and 3 N-glycan peaks (m/z 2240.830, 2507.914, and 3931.338) were unique in HCC group. 28389847 7 50 dep peaks 1184:1188 arg1 2580.930 1215:1222 2580.930 1215:1222 2580.930 1215:1222 Three N-glycan peaks (m/z 2596.925, 2756.962, and 2921.031) were unique in HV group, 2 N-glycan peaks (m/z 1898.676 and 1971.692) were unique in HB group, 5 N-glycan peaks (m/z 1954.677, 2507.914, 2580.930, 2637.952, and 3092.120) were unique in HC group, and 3 N-glycan peaks (m/z 2240.830, 2507.914, and 3931.338) were unique in HCC group. 28389847 7 50 dep peaks 1184:1188 arg1 2507.914 1205:1212 2507.914 1205:1212 2507.914 1205:1212 Three N-glycan peaks (m/z 2596.925, 2756.962, and 2921.031) were unique in HV group, 2 N-glycan peaks (m/z 1898.676 and 1971.692) were unique in HB group, 5 N-glycan peaks (m/z 1954.677, 2507.914, 2580.930, 2637.952, and 3092.120) were unique in HC group, and 3 N-glycan peaks (m/z 2240.830, 2507.914, and 3931.338) were unique in HCC group. 28389847 3 51 theme hepatocellular 612:625 arg1 HCC 647:649 HCC 647:649 HCC 647:649 Here we investigated N-linked glycome in saliva from 200 subjects (50 healthy volunteers (HV), 40 HBV-infected patients (HB), 50 cirrhosis patients (HC), and 60 hepatocellular carcinoma patients (HCC) using MALDI-TOF/TOF-MS. 28389847 3 51 theme hepatocellular 612:625 arg1 patients 637:644 60 hepatocellular carcinoma patients 609:644 60 hepatocellular carcinoma patients (HCC) 609:650 Here we investigated N-linked glycome in saliva from 200 subjects (50 healthy volunteers (HV), 40 HBV-infected patients (HB), 50 cirrhosis patients (HC), and 60 hepatocellular carcinoma patients (HCC) using MALDI-TOF/TOF-MS. 28389847 8 52 theme HCC 1555:1557 arg1 group 1559:1563 HCC group 1555:1563 HCC group (12.1%) 1555:1571 The proportion of fucosylated N-glycans was apparently increased in the HCC group (84.8%) than in any other group (73.1% ± 0.01), however, the proportion of sialylated N-glycans was decreased in HCC group (12.1%) than in any other group (17.23% ± 0.003). 28389847 8 52 theme HCC 1555:1557 arg1 % 1570:1570 12.1% 1566:1570 12.1% 1566:1570 The proportion of fucosylated N-glycans was apparently increased in the HCC group (84.8%) than in any other group (73.1% ± 0.01), however, the proportion of sialylated N-glycans was decreased in HCC group (12.1%) than in any other group (17.23% ± 0.003). 28389847 3 53 theme N-linked 472:479 arg1 glycome 481:487 N-linked glycome 472:487 N-linked glycome in saliva from 200 subjects (50 healthy volunteers (HV), 40 HBV-infected patients (HB), 50 cirrhosis patients (HC), and 60 hepatocellular carcinoma patients (HCC) 472:650 Here we investigated N-linked glycome in saliva from 200 subjects (50 healthy volunteers (HV), 40 HBV-infected patients (HB), 50 cirrhosis patients (HC), and 60 hepatocellular carcinoma patients (HCC) using MALDI-TOF/TOF-MS. 28389847 9 54 theme early 1782:1786 arg1 stages 1788:1793 its early stages 1778:1793 its early stages based on precise alterations of N-linked glycans 1778:1842 Our data provide pivotal information to distinguish between HBV-associated hepatitis, cirrhosis and HCC, and facilitate the discovery of biomarkers for HCC during its early stages based on precise alterations of N-linked glycans in saliva. 28389847 8 55 theme HCC 1432:1434 arg1 group 1436:1440 the HCC group 1428:1440 the HCC group (84.8%) 1428:1448 The proportion of fucosylated N-glycans was apparently increased in the HCC group (84.8%) than in any other group (73.1% ± 0.01), however, the proportion of sialylated N-glycans was decreased in HCC group (12.1%) than in any other group (17.23% ± 0.003). 28389847 8 55 theme HCC 1432:1434 arg1 % 1447:1447 84.8% 1443:1447 84.8% 1443:1447 The proportion of fucosylated N-glycans was apparently increased in the HCC group (84.8%) than in any other group (73.1% ± 0.01), however, the proportion of sialylated N-glycans was decreased in HCC group (12.1%) than in any other group (17.23% ± 0.003). 28389847 7 56 from unique 1083:1088 arg1 group 1096:1100 HV group 1093:1100 HV group 1093:1100 Three N-glycan peaks (m/z 2596.925, 2756.962, and 2921.031) were unique in HV group, 2 N-glycan peaks (m/z 1898.676 and 1971.692) were unique in HB group, 5 N-glycan peaks (m/z 1954.677, 2507.914, 2580.930, 2637.952, and 3092.120) were unique in HC group, and 3 N-glycan peaks (m/z 2240.830, 2507.914, and 3931.338) were unique in HCC group. 28389847 1 57 theme hepatitis 187:195 arg1 HBV 206:208 HBV 206:208 HBV 206:208 Hepatitis B is a potentially life-threatening liver infection caused by the hepatitis B virus (HBV), which can lead to chronic liver disease and put people at high risk of death from cirrhosis of the liver and liver cancer. 28389847 1 57 theme hepatitis 187:195 arg1 virus 199:203 the hepatitis B virus 183:203 the hepatitis B virus (HBV) 183:209 Hepatitis B is a potentially life-threatening liver infection caused by the hepatitis B virus (HBV), which can lead to chronic liver disease and put people at high risk of death from cirrhosis of the liver and liver cancer. 28389847 5 58 theme 40 806:807 arg1 total 797:801 A total 795:801 A total of 40, 47, 29, and 33 N-glycan peaks 795:838 A total of 40, 47, 29, and 33 N-glycan peaks were identified and annotated from HV, HB, HC, and HCC groups, respectively. 28389847 3 59 from patients 590:597 arg1 glycome 481:487 N-linked glycome 472:487 N-linked glycome in saliva from 200 subjects (50 healthy volunteers (HV), 40 HBV-infected patients (HB), 50 cirrhosis patients (HC), and 60 hepatocellular carcinoma patients (HCC) 472:650 Here we investigated N-linked glycome in saliva from 200 subjects (50 healthy volunteers (HV), 40 HBV-infected patients (HB), 50 cirrhosis patients (HC), and 60 hepatocellular carcinoma patients (HCC) using MALDI-TOF/TOF-MS. 28389847 9 60 theme precise 1804:1810 arg1 alterations 1812:1822 precise alterations 1804:1822 precise alterations of N-linked glycans 1804:1842 Our data provide pivotal information to distinguish between HBV-associated hepatitis, cirrhosis and HCC, and facilitate the discovery of biomarkers for HCC during its early stages based on precise alterations of N-linked glycans in saliva. 28389847 1 61 theme cancer 327:332 arg1 cirrhosis 294:302 cirrhosis 294:302 cirrhosis of the liver and liver cancer 294:332 Hepatitis B is a potentially life-threatening liver infection caused by the hepatitis B virus (HBV), which can lead to chronic liver disease and put people at high risk of death from cirrhosis of the liver and liver cancer. 28389847 8 62 dep increased 1415:1423 arg1 % 1479:1479 73.1% ± 0.01 1475:1486 73.1% ± 0.01 1475:1486 The proportion of fucosylated N-glycans was apparently increased in the HCC group (84.8%) than in any other group (73.1% ± 0.01), however, the proportion of sialylated N-glycans was decreased in HCC group (12.1%) than in any other group (17.23% ± 0.003). 28389847 9 63 theme glycans 1836:1842 arg1 alterations 1812:1822 precise alterations 1804:1822 precise alterations of N-linked glycans 1804:1842 Our data provide pivotal information to distinguish between HBV-associated hepatitis, cirrhosis and HCC, and facilitate the discovery of biomarkers for HCC during its early stages based on precise alterations of N-linked glycans in saliva. 28389847 3 64 from subjects 508:515 arg1 glycome 481:487 N-linked glycome 472:487 N-linked glycome in saliva from 200 subjects (50 healthy volunteers (HV), 40 HBV-infected patients (HB), 50 cirrhosis patients (HC), and 60 hepatocellular carcinoma patients (HCC) 472:650 Here we investigated N-linked glycome in saliva from 200 subjects (50 healthy volunteers (HV), 40 HBV-infected patients (HB), 50 cirrhosis patients (HC), and 60 hepatocellular carcinoma patients (HCC) using MALDI-TOF/TOF-MS. 28389847 1 65 theme Hepatitis 111:119 arg1 B 121:121 Hepatitis B 111:121 Hepatitis B 111:121 Hepatitis B is a potentially life-threatening liver infection caused by the hepatitis B virus (HBV), which can lead to chronic liver disease and put people at high risk of death from cirrhosis of the liver and liver cancer. 28389847 1 65 theme Hepatitis 111:119 arg1 infection 163:171 a potentially life-threatening liver infection 126:171 a potentially life-threatening liver infection caused by the hepatitis B virus (HBV), which can lead to chronic liver disease and put people at high risk of death from cirrhosis of the liver and liver cancer 126:332 Hepatitis B is a potentially life-threatening liver infection caused by the hepatitis B virus (HBV), which can lead to chronic liver disease and put people at high risk of death from cirrhosis of the liver and liver cancer. 28389847 2 66 theme liver 435:439 arg1 diseases 441:448 HBV-infected liver diseases 422:448 HBV-infected liver diseases 422:448 However, little is known about the correlation of salivary N-linked glycans related to HBV-infected liver diseases. 28389847 1 67 theme death 283:287 arg1 risk 275:278 high risk 270:278 high risk of death from cirrhosis of the liver and liver cancer 270:332 Hepatitis B is a potentially life-threatening liver infection caused by the hepatitis B virus (HBV), which can lead to chronic liver disease and put people at high risk of death from cirrhosis of the liver and liver cancer. 28389847 1 68 theme life-threatening 140:155 arg1 B 121:121 Hepatitis B 111:121 Hepatitis B 111:121 Hepatitis B is a potentially life-threatening liver infection caused by the hepatitis B virus (HBV), which can lead to chronic liver disease and put people at high risk of death from cirrhosis of the liver and liver cancer. 28389847 1 68 theme life-threatening 140:155 arg1 infection 163:171 a potentially life-threatening liver infection 126:171 a potentially life-threatening liver infection caused by the hepatitis B virus (HBV), which can lead to chronic liver disease and put people at high risk of death from cirrhosis of the liver and liver cancer 126:332 Hepatitis B is a potentially life-threatening liver infection caused by the hepatitis B virus (HBV), which can lead to chronic liver disease and put people at high risk of death from cirrhosis of the liver and liver cancer. 28389847 4 69 with spectra 694:700 arg1 ratios 736:741 signal-to-noise ratios >6 720:744 signal-to-noise ratios >6 720:744 Representative MS spectra of N-glycans with signal-to-noise ratios >6 were annotated using the GlycoWorkbench program. 28389847 7 70 theme N-glycan 1024:1031 arg1 m/z 1040:1042 m/z 2596.925, 2756.962, and 2921.031 1040:1075 m/z 2596.925, 2756.962, and 2921.031 1040:1075 Three N-glycan peaks (m/z 2596.925, 2756.962, and 2921.031) were unique in HV group, 2 N-glycan peaks (m/z 1898.676 and 1971.692) were unique in HB group, 5 N-glycan peaks (m/z 1954.677, 2507.914, 2580.930, 2637.952, and 3092.120) were unique in HC group, and 3 N-glycan peaks (m/z 2240.830, 2507.914, and 3931.338) were unique in HCC group. 28389847 7 70 theme N-glycan 1024:1031 arg1 peaks 1033:1037 Three N-glycan peaks 1018:1037 Three N-glycan peaks (m/z 2596.925, 2756.962, and 2921.031) 1018:1076 Three N-glycan peaks (m/z 2596.925, 2756.962, and 2921.031) were unique in HV group, 2 N-glycan peaks (m/z 1898.676 and 1971.692) were unique in HB group, 5 N-glycan peaks (m/z 1954.677, 2507.914, 2580.930, 2637.952, and 3092.120) were unique in HC group, and 3 N-glycan peaks (m/z 2240.830, 2507.914, and 3931.338) were unique in HCC group. 28389847 4 71 theme Representative 676:689 arg1 spectra 694:700 Representative MS spectra 676:700 Representative MS spectra of N-glycans with signal-to-noise ratios >6 676:744 Representative MS spectra of N-glycans with signal-to-noise ratios >6 were annotated using the GlycoWorkbench program. 28389847 7 72 theme 5 N-glycan 1173:1182 arg1 peaks 1184:1188 5 N-glycan peaks 1173:1188 5 N-glycan peaks (m/z 1954.677, 2507.914, 2580.930, 2637.952, and 3092.120) 1173:1247 Three N-glycan peaks (m/z 2596.925, 2756.962, and 2921.031) were unique in HV group, 2 N-glycan peaks (m/z 1898.676 and 1971.692) were unique in HB group, 5 N-glycan peaks (m/z 1954.677, 2507.914, 2580.930, 2637.952, and 3092.120) were unique in HC group, and 3 N-glycan peaks (m/z 2240.830, 2507.914, and 3931.338) were unique in HCC group. 28389847 6 73 theme 15 N-glycan 928:938 arg1 peaks 940:944 15 N-glycan peaks 928:944 15 N-glycan peaks (e.g., m/z 1647.587, 1688.613 and 2101.755) were present in all groups 928:1015 There were 15 N-glycan peaks (e.g., m/z 1647.587, 1688.613 and 2101.755) were present in all groups. 28389847 3 74 from patients 637:644 arg1 glycome 481:487 N-linked glycome 472:487 N-linked glycome in saliva from 200 subjects (50 healthy volunteers (HV), 40 HBV-infected patients (HB), 50 cirrhosis patients (HC), and 60 hepatocellular carcinoma patients (HCC) 472:650 Here we investigated N-linked glycome in saliva from 200 subjects (50 healthy volunteers (HV), 40 HBV-infected patients (HB), 50 cirrhosis patients (HC), and 60 hepatocellular carcinoma patients (HCC) using MALDI-TOF/TOF-MS. 28389847 2 75 link N-linked 394:401 arg1 glycans 403:409 salivary N-linked glycans 385:409 salivary N-linked glycans related to HBV-infected liver diseases 385:448 However, little is known about the correlation of salivary N-linked glycans related to HBV-infected liver diseases. 28389847 6 76 from groups 1010:1015 arg1 present 995:1001 present 995:1001 present 995:1001 There were 15 N-glycan peaks (e.g., m/z 1647.587, 1688.613 and 2101.755) were present in all groups. 28389847 0 77 theme pilot 2:6 arg1 study 8:12 A pilot study 0:12 A pilot study of salivary N-glycome in HBV-induced chronic hepatitis, cirrhosis, and hepatocellular carcinoma 0:108 A pilot study of salivary N-glycome in HBV-induced chronic hepatitis, cirrhosis, and hepatocellular carcinoma. 28389847 7 78 from group 1353:1357 arg1 unique 1339:1344 unique 1339:1344 unique 1339:1344 Three N-glycan peaks (m/z 2596.925, 2756.962, and 2921.031) were unique in HV group, 2 N-glycan peaks (m/z 1898.676 and 1971.692) were unique in HB group, 5 N-glycan peaks (m/z 1954.677, 2507.914, 2580.930, 2637.952, and 3092.120) were unique in HC group, and 3 N-glycan peaks (m/z 2240.830, 2507.914, and 3931.338) were unique in HCC group. 28389847 9 79 theme HBV-associated 1675:1688 arg1 hepatitis 1690:1698 HBV-associated hepatitis 1675:1698 HBV-associated hepatitis 1675:1698 Our data provide pivotal information to distinguish between HBV-associated hepatitis, cirrhosis and HCC, and facilitate the discovery of biomarkers for HCC during its early stages based on precise alterations of N-linked glycans in saliva. 28389847 5 80 theme 33 N-glycan 822:832 arg1 peaks 834:838 33 N-glycan peaks 822:838 33 N-glycan peaks 822:838 A total of 40, 47, 29, and 33 N-glycan peaks were identified and annotated from HV, HB, HC, and HCC groups, respectively. 28389847 3 81 from volunteers 529:538 arg1 glycome 481:487 N-linked glycome 472:487 N-linked glycome in saliva from 200 subjects (50 healthy volunteers (HV), 40 HBV-infected patients (HB), 50 cirrhosis patients (HC), and 60 hepatocellular carcinoma patients (HCC) 472:650 Here we investigated N-linked glycome in saliva from 200 subjects (50 healthy volunteers (HV), 40 HBV-infected patients (HB), 50 cirrhosis patients (HC), and 60 hepatocellular carcinoma patients (HCC) using MALDI-TOF/TOF-MS. 28389847 0 82 theme N-glycome 26:34 arg1 study 8:12 A pilot study 0:12 A pilot study of salivary N-glycome in HBV-induced chronic hepatitis, cirrhosis, and hepatocellular carcinoma 0:108 A pilot study of salivary N-glycome in HBV-induced chronic hepatitis, cirrhosis, and hepatocellular carcinoma. 28389847 7 83 theme 3 N-glycan 1278:1287 arg1 m/z 1296:1298 m/z 2240.830, 2507.914, and 3931.338 1296:1331 m/z 2240.830, 2507.914, and 3931.338 1296:1331 Three N-glycan peaks (m/z 2596.925, 2756.962, and 2921.031) were unique in HV group, 2 N-glycan peaks (m/z 1898.676 and 1971.692) were unique in HB group, 5 N-glycan peaks (m/z 1954.677, 2507.914, 2580.930, 2637.952, and 3092.120) were unique in HC group, and 3 N-glycan peaks (m/z 2240.830, 2507.914, and 3931.338) were unique in HCC group. 28389847 7 83 theme 3 N-glycan 1278:1287 arg1 peaks 1289:1293 3 N-glycan peaks 1278:1293 3 N-glycan peaks (m/z 2240.830, 2507.914, and 3931.338) 1278:1332 Three N-glycan peaks (m/z 2596.925, 2756.962, and 2921.031) were unique in HV group, 2 N-glycan peaks (m/z 1898.676 and 1971.692) were unique in HB group, 5 N-glycan peaks (m/z 1954.677, 2507.914, 2580.930, 2637.952, and 3092.120) were unique in HC group, and 3 N-glycan peaks (m/z 2240.830, 2507.914, and 3931.338) were unique in HCC group. 28389847 7 84 from group 1166:1170 arg1 unique 1153:1158 unique 1153:1158 unique 1153:1158 Three N-glycan peaks (m/z 2596.925, 2756.962, and 2921.031) were unique in HV group, 2 N-glycan peaks (m/z 1898.676 and 1971.692) were unique in HB group, 5 N-glycan peaks (m/z 1954.677, 2507.914, 2580.930, 2637.952, and 3092.120) were unique in HC group, and 3 N-glycan peaks (m/z 2240.830, 2507.914, and 3931.338) were unique in HCC group. 28389847 7 85 theme HV 1093:1094 arg1 group 1096:1100 HV group 1093:1100 HV group 1093:1100 Three N-glycan peaks (m/z 2596.925, 2756.962, and 2921.031) were unique in HV group, 2 N-glycan peaks (m/z 1898.676 and 1971.692) were unique in HB group, 5 N-glycan peaks (m/z 1954.677, 2507.914, 2580.930, 2637.952, and 3092.120) were unique in HC group, and 3 N-glycan peaks (m/z 2240.830, 2507.914, and 3931.338) were unique in HCC group. 28389847 2 86 theme glycans 403:409 arg1 correlation 370:380 the correlation 366:380 the correlation of salivary N-linked glycans related to HBV-infected liver diseases 366:448 However, little is known about the correlation of salivary N-linked glycans related to HBV-infected liver diseases. 28389847 3 87 theme HBV-infected 549:560 arg1 HB 572:573 HB 572:573 HB 572:573 Here we investigated N-linked glycome in saliva from 200 subjects (50 healthy volunteers (HV), 40 HBV-infected patients (HB), 50 cirrhosis patients (HC), and 60 hepatocellular carcinoma patients (HCC) using MALDI-TOF/TOF-MS. 28389847 3 87 theme HBV-infected 549:560 arg1 patients 562:569 40 HBV-infected patients 546:569 40 HBV-infected patients (HB) 546:574 Here we investigated N-linked glycome in saliva from 200 subjects (50 healthy volunteers (HV), 40 HBV-infected patients (HB), 50 cirrhosis patients (HC), and 60 hepatocellular carcinoma patients (HCC) using MALDI-TOF/TOF-MS. 28389847 4 88 theme N-glycans 705:713 arg1 spectra 694:700 Representative MS spectra 676:700 Representative MS spectra of N-glycans with signal-to-noise ratios >6 676:744 Representative MS spectra of N-glycans with signal-to-noise ratios >6 were annotated using the GlycoWorkbench program. 28389847 0 89 theme HBV-induced 39:49 arg1 hepatitis 59:67 HBV-induced chronic hepatitis 39:67 HBV-induced chronic hepatitis 39:67 A pilot study of salivary N-glycome in HBV-induced chronic hepatitis, cirrhosis, and hepatocellular carcinoma. 28389847 7 90 from group 1096:1100 arg1 unique 1083:1088 unique 1083:1088 unique 1083:1088 Three N-glycan peaks (m/z 2596.925, 2756.962, and 2921.031) were unique in HV group, 2 N-glycan peaks (m/z 1898.676 and 1971.692) were unique in HB group, 5 N-glycan peaks (m/z 1954.677, 2507.914, 2580.930, 2637.952, and 3092.120) were unique in HC group, and 3 N-glycan peaks (m/z 2240.830, 2507.914, and 3931.338) were unique in HCC group. 28389847 2 91 theme salivary 385:392 arg1 glycans 403:409 salivary N-linked glycans 385:409 salivary N-linked glycans related to HBV-infected liver diseases 385:448 However, little is known about the correlation of salivary N-linked glycans related to HBV-infected liver diseases. 28389847 4 92 theme signal-to-noise 720:734 arg1 ratios 736:741 signal-to-noise ratios >6 720:744 signal-to-noise ratios >6 720:744 Representative MS spectra of N-glycans with signal-to-noise ratios >6 were annotated using the GlycoWorkbench program. 28389847 7 93 theme HC 1264:1265 arg1 group 1267:1271 HC group 1264:1271 HC group 1264:1271 Three N-glycan peaks (m/z 2596.925, 2756.962, and 2921.031) were unique in HV group, 2 N-glycan peaks (m/z 1898.676 and 1971.692) were unique in HB group, 5 N-glycan peaks (m/z 1954.677, 2507.914, 2580.930, 2637.952, and 3092.120) were unique in HC group, and 3 N-glycan peaks (m/z 2240.830, 2507.914, and 3931.338) were unique in HCC group. 28389847 6 94 dep m/z 953:955 arg1 e.g. 947:950 e.g. 947:950 e.g. 947:950 There were 15 N-glycan peaks (e.g., m/z 1647.587, 1688.613 and 2101.755) were present in all groups. 28389847 8 95 theme fucosylated 1378:1388 arg1 N-glycans 1390:1398 fucosylated N-glycans 1378:1398 fucosylated N-glycans 1378:1398 The proportion of fucosylated N-glycans was apparently increased in the HCC group (84.8%) than in any other group (73.1% ± 0.01), however, the proportion of sialylated N-glycans was decreased in HCC group (12.1%) than in any other group (17.23% ± 0.003). 28220142 12 0 theme genomic 2161:2167 arg1 RNA 2169:2171 genomic RNA 2161:2171 elevated genomic RNA expression 2152:2182 Our results demonstrate that recombinant JUNV (rJUNV) expressing Can GPC display markedly different protein expression and elevated genomic RNA expression when compared to viruses expressing Rom GPC. 28220142 6 1 theme intra-segment 979:991 arg1 clones 1019:1024 both inter- and intra-segment chimeric JUNV recombinant clones 963:1024 both inter- and intra-segment chimeric JUNV recombinant clones expressing combinations of genes from the Can strain and the pathogenic Romero (Rom) strain 963:1116 Here, we provide a detailed comparison of both RNA and protein expression profiles between both inter- and intra-segment chimeric JUNV recombinant clones expressing combinations of genes from the Can strain and the pathogenic Romero (Rom) strain. 28220142 0 2 theme Improper 149:156 arg1 Processing 158:167 Its Improper Processing 145:167 Its Improper Processing 145:167 Absence of an N-Linked Glycosylation Motif in the Glycoprotein of the Live-Attenuated Argentine Hemorrhagic Fever Vaccine, Candid #1, Results in Its Improper Processing, and Reduced Surface Expression. 28220142 11 3 theme GPC 1993:1995 arg1 expression 1997:2006 significantly increased GPC expression 1969:2006 significantly increased GPC expression 1969:2006 Interestingly, the reversion A168T in Can GPC significantly increased GPC expression at the cell surface. 28220142 7 4 theme Western 1304:1310 arg1 analyses 1317:1324 Western blot analyses 1304:1324 Western blot analyses 1304:1324 The recombinant viruses that express Can GPC, which were shown to be attenuated in guinea pigs, displayed different RNA levels and GPC processing patterns as determined by Northern and Western blot analyses, respectively. 28220142 7 5 theme recombinant 1123:1133 arg1 viruses 1135:1141 The recombinant viruses 1119:1141 The recombinant viruses that express Can GPC 1119:1162 The recombinant viruses that express Can GPC, which were shown to be attenuated in guinea pigs, displayed different RNA levels and GPC processing patterns as determined by Northern and Western blot analyses, respectively. 28220142 3 6 dep the 453:455 arg1 Can 457:459 Can 457:459 Can 457:459 We have previously shown that the Can glycoprotein (GPC) gene is the primary gene responsible for attenuation in a guinea pig model of AHF. 28220142 10 7 theme endoplasmic 1814:1824 arg1 ER 1837:1838 ER 1837:1838 ER 1837:1838 In addition, JUNV GPCs containing T168A substitution were retained within the endoplasmic reticulum (ER) and displayed significantly lower cell surface expression than wild-type Rom GPC. 28220142 10 7 theme endoplasmic 1814:1824 arg1 reticulum 1826:1834 the endoplasmic reticulum 1810:1834 the endoplasmic reticulum (ER) 1810:1839 In addition, JUNV GPCs containing T168A substitution were retained within the endoplasmic reticulum (ER) and displayed significantly lower cell surface expression than wild-type Rom GPC. 28220142 0 8 theme Reduced 174:180 arg1 Expression 190:199 Reduced Surface Expression 174:199 Reduced Surface Expression 174:199 Absence of an N-Linked Glycosylation Motif in the Glycoprotein of the Live-Attenuated Argentine Hemorrhagic Fever Vaccine, Candid #1, Results in Its Improper Processing, and Reduced Surface Expression. 28220142 8 9 theme glycosylation 1606:1618 arg1 motif 1620:1624 an N-linked glycosylation motif 1594:1624 an N-linked glycosylation motif 1594:1624 Analysis of recombinant viruses containing amino acid substitutions selected at different mouse brain passages during the generation of Can revealed that altered Can GPC processing was primarily due to the T168A substitution within G1, which eliminates an N-linked glycosylation motif. 28220142 13 10 from ER 2472:2473 arg1 release 2455:2461 the GPC release 2447:2461 the GPC release from the ER 2447:2473 Additionally, our findings indicate that the N-linked glycosylation motif at amino acid positions 166-168 is important for trafficking of JUNV GPC to the cell surface, and the elimination of this motif interferes with the GPC release from the ER. 28220142 11 11 theme cell 2015:2018 arg1 surface 2020:2026 the cell surface 2011:2026 the cell surface 2011:2026 Interestingly, the reversion A168T in Can GPC significantly increased GPC expression at the cell surface. 28220142 6 12 dep the 1064:1066 arg1 Can 1068:1070 Can 1068:1070 Can 1068:1070 Here, we provide a detailed comparison of both RNA and protein expression profiles between both inter- and intra-segment chimeric JUNV recombinant clones expressing combinations of genes from the Can strain and the pathogenic Romero (Rom) strain. 28220142 13 13 theme motif 2425:2429 arg1 elimination 2405:2415 the elimination 2401:2415 the elimination of this motif 2401:2429 Additionally, our findings indicate that the N-linked glycosylation motif at amino acid positions 166-168 is important for trafficking of JUNV GPC to the cell surface, and the elimination of this motif interferes with the GPC release from the ER. 28220142 6 14 theme genes 1053:1057 arg1 combinations 1037:1048 combinations 1037:1048 combinations of genes 1037:1057 Here, we provide a detailed comparison of both RNA and protein expression profiles between both inter- and intra-segment chimeric JUNV recombinant clones expressing combinations of genes from the Can strain and the pathogenic Romero (Rom) strain. 28220142 13 15 theme acid 2312:2315 arg1 positions 2317:2325 amino acid positions 166-168 2306:2333 amino acid positions 166-168 2306:2333 Additionally, our findings indicate that the N-linked glycosylation motif at amino acid positions 166-168 is important for trafficking of JUNV GPC to the cell surface, and the elimination of this motif interferes with the GPC release from the ER. 28220142 13 16 theme cell 2383:2386 arg1 surface 2388:2394 the cell surface 2379:2394 the cell surface 2379:2394 Additionally, our findings indicate that the N-linked glycosylation motif at amino acid positions 166-168 is important for trafficking of JUNV GPC to the cell surface, and the elimination of this motif interferes with the GPC release from the ER. 28220142 8 17 dep revealed 1481:1488 arg1 altered 1495:1501 altered 1495:1501 altered 1495:1501 Analysis of recombinant viruses containing amino acid substitutions selected at different mouse brain passages during the generation of Can revealed that altered Can GPC processing was primarily due to the T168A substitution within G1, which eliminates an N-linked glycosylation motif. 28220142 8 17 dep revealed 1481:1488 arg1 generation 1463:1472 the generation 1459:1472 the generation of Can revealed that altered Can GPC processing was primarily due to the T168A substitution within G1, which eliminates an N-linked glycosylation motif 1459:1624 Analysis of recombinant viruses containing amino acid substitutions selected at different mouse brain passages during the generation of Can revealed that altered Can GPC processing was primarily due to the T168A substitution within G1, which eliminates an N-linked glycosylation motif. 28220142 7 18 theme GPC 1250:1252 arg1 patterns 1265:1272 GPC processing patterns 1250:1272 GPC processing patterns 1250:1272 The recombinant viruses that express Can GPC, which were shown to be attenuated in guinea pigs, displayed different RNA levels and GPC processing patterns as determined by Northern and Western blot analyses, respectively. 28220142 10 19 theme surface 1880:1886 arg1 expression 1888:1897 significantly lower cell surface expression 1855:1897 significantly lower cell surface expression 1855:1897 In addition, JUNV GPCs containing T168A substitution were retained within the endoplasmic reticulum (ER) and displayed significantly lower cell surface expression than wild-type Rom GPC. 28220142 3 20 theme responsible 505:515 arg1 gene 500:503 the primary gene 488:503 the primary gene responsible for attenuation in a guinea pig model of AHF 488:560 We have previously shown that the Can glycoprotein (GPC) gene is the primary gene responsible for attenuation in a guinea pig model of AHF. 28220142 3 20 theme responsible 505:515 arg1 the 453:455 the 453:455 the 453:455 We have previously shown that the Can glycoprotein (GPC) gene is the primary gene responsible for attenuation in a guinea pig model of AHF. 28220142 0 21 from Glycoprotein 50:61 arg1 # 130:130 Candid #1 123:131 Candid #1 123:131 Absence of an N-Linked Glycosylation Motif in the Glycoprotein of the Live-Attenuated Argentine Hemorrhagic Fever Vaccine, Candid #1, Results in Its Improper Processing, and Reduced Surface Expression. 28220142 0 21 from Glycoprotein 50:61 arg1 Absence 0:6 Absence 0:6 Absence of an N-Linked Glycosylation Motif in the Glycoprotein of the Live-Attenuated Argentine Hemorrhagic Fever Vaccine 0:120 Absence of an N-Linked Glycosylation Motif in the Glycoprotein of the Live-Attenuated Argentine Hemorrhagic Fever Vaccine, Candid #1, Results in Its Improper Processing, and Reduced Surface Expression. 28220142 10 22 theme lower 1869:1873 arg1 expression 1888:1897 significantly lower cell surface expression 1855:1897 significantly lower cell surface expression 1855:1897 In addition, JUNV GPCs containing T168A substitution were retained within the endoplasmic reticulum (ER) and displayed significantly lower cell surface expression than wild-type Rom GPC. 28220142 13 23 theme JUNV 2367:2370 arg1 GPC 2372:2374 JUNV GPC 2367:2374 JUNV GPC 2367:2374 Additionally, our findings indicate that the N-linked glycosylation motif at amino acid positions 166-168 is important for trafficking of JUNV GPC to the cell surface, and the elimination of this motif interferes with the GPC release from the ER. 28220142 3 24 theme primary 492:498 arg1 gene 500:503 the primary gene 488:503 the primary gene responsible for attenuation in a guinea pig model of AHF 488:560 We have previously shown that the Can glycoprotein (GPC) gene is the primary gene responsible for attenuation in a guinea pig model of AHF. 28220142 3 24 theme primary 492:498 arg1 the 453:455 the 453:455 the 453:455 We have previously shown that the Can glycoprotein (GPC) gene is the primary gene responsible for attenuation in a guinea pig model of AHF. 28220142 7 25 theme different 1225:1233 arg1 levels 1239:1244 different RNA levels 1225:1244 different RNA levels 1225:1244 The recombinant viruses that express Can GPC, which were shown to be attenuated in guinea pigs, displayed different RNA levels and GPC processing patterns as determined by Northern and Western blot analyses, respectively. 28220142 6 26 theme Rom 1106:1108 arg1 strain 1111:1116 the pathogenic Romero (Rom) strain 1083:1116 the pathogenic Romero (Rom) strain 1083:1116 Here, we provide a detailed comparison of both RNA and protein expression profiles between both inter- and intra-segment chimeric JUNV recombinant clones expressing combinations of genes from the Can strain and the pathogenic Romero (Rom) strain. 28220142 10 27 theme Rom 1914:1916 arg1 GPC 1918:1920 wild-type Rom GPC 1904:1920 wild-type Rom GPC 1904:1920 In addition, JUNV GPCs containing T168A substitution were retained within the endoplasmic reticulum (ER) and displayed significantly lower cell surface expression than wild-type Rom GPC. 28220142 8 28 theme recombinant 1353:1363 arg1 viruses 1365:1371 recombinant viruses 1353:1371 recombinant viruses containing amino acid substitutions 1353:1407 Analysis of recombinant viruses containing amino acid substitutions selected at different mouse brain passages during the generation of Can revealed that altered Can GPC processing was primarily due to the T168A substitution within G1, which eliminates an N-linked glycosylation motif. 28220142 13 29 dep positions 2317:2325 arg1 166-168 2327:2333 166-168 2327:2333 166-168 2327:2333 Additionally, our findings indicate that the N-linked glycosylation motif at amino acid positions 166-168 is important for trafficking of JUNV GPC to the cell surface, and the elimination of this motif interferes with the GPC release from the ER. 28220142 6 30 theme detailed 891:898 arg1 comparison 900:909 a detailed comparison 889:909 a detailed comparison of both RNA and protein expression profiles between both inter- and intra-segment chimeric JUNV recombinant clones expressing combinations of genes from the Can strain and the pathogenic Romero (Rom) strain 889:1116 Here, we provide a detailed comparison of both RNA and protein expression profiles between both inter- and intra-segment chimeric JUNV recombinant clones expressing combinations of genes from the Can strain and the pathogenic Romero (Rom) strain. 28220142 9 31 theme substitution 1654:1665 arg1 Incorporation 1627:1639 Incorporation 1627:1639 Incorporation of the T168A substitution in the Rom GPC 1627:1680 Incorporation of the T168A substitution in the Rom GPC resulted in a Can-like processing pattern of Rom GPC. 28220142 1 32 theme Argentine 290:298 arg1 AHF 319:321 AHF 319:321 AHF 319:321 Junin virus (JUNV), a highly pathogenic New World arenavirus, is the causative agent of Argentine hemorrhagic fever (AHF). 28220142 1 32 theme Argentine 290:298 arg1 fever 312:316 Argentine hemorrhagic fever 290:316 Argentine hemorrhagic fever (AHF) 290:322 Junin virus (JUNV), a highly pathogenic New World arenavirus, is the causative agent of Argentine hemorrhagic fever (AHF). 28220142 0 33 from Absence 0:6 arg1 Glycoprotein 50:61 the Glycoprotein 46:61 the Glycoprotein of the Live-Attenuated Argentine Hemorrhagic Fever Vaccine 46:120 Absence of an N-Linked Glycosylation Motif in the Glycoprotein of the Live-Attenuated Argentine Hemorrhagic Fever Vaccine, Candid #1, Results in Its Improper Processing, and Reduced Surface Expression. 28220142 12 34 theme different 2119:2127 arg1 expression 2137:2146 markedly different protein expression 2110:2146 markedly different protein expression 2110:2146 Our results demonstrate that recombinant JUNV (rJUNV) expressing Can GPC display markedly different protein expression and elevated genomic RNA expression when compared to viruses expressing Rom GPC. 28220142 0 35 theme Argentine 86:94 arg1 Fever 108:112 the Live-Attenuated Argentine Hemorrhagic Fever 66:112 the Live-Attenuated Argentine Hemorrhagic Fever Vaccine 66:120 Absence of an N-Linked Glycosylation Motif in the Glycoprotein of the Live-Attenuated Argentine Hemorrhagic Fever Vaccine, Candid #1, Results in Its Improper Processing, and Reduced Surface Expression. 28220142 1 36 theme fever 312:316 arg1 agent 281:285 the causative agent 267:285 the causative agent of Argentine hemorrhagic fever (AHF) 267:322 Junin virus (JUNV), a highly pathogenic New World arenavirus, is the causative agent of Argentine hemorrhagic fever (AHF). 28220142 1 36 theme fever 312:316 arg1 virus 208:212 Junin virus 202:212 Junin virus (JUNV) 202:219 Junin virus (JUNV), a highly pathogenic New World arenavirus, is the causative agent of Argentine hemorrhagic fever (AHF). 28220142 5 37 theme vaccines 862:869 arg1 design 826:831 the rational design 813:831 the rational design of additional safe and novel vaccines 813:869 A more complete understanding of the mechanisms underlying the attenuation and immunogenicity of the Can strain will potentially allow for the rational design of additional safe and novel vaccines. 28220142 3 38 from attenuation 521:531 arg1 model 549:553 a guinea pig model 536:553 a guinea pig model of AHF 536:560 We have previously shown that the Can glycoprotein (GPC) gene is the primary gene responsible for attenuation in a guinea pig model of AHF. 28220142 2 39 theme Candid 345:350 arg1 # 352:352 Candid #1 345:353 The live-attenuated Candid #1 (Can) strain 325:366 The live-attenuated Candid #1 (Can) strain currently serves as a vaccine for at-risk populations. 28220142 0 40 theme Fever 108:112 arg1 Vaccine 114:120 the Live-Attenuated Argentine Hemorrhagic Fever Vaccine 66:120 the Live-Attenuated Argentine Hemorrhagic Fever Vaccine 66:120 Absence of an N-Linked Glycosylation Motif in the Glycoprotein of the Live-Attenuated Argentine Hemorrhagic Fever Vaccine, Candid #1, Results in Its Improper Processing, and Reduced Surface Expression. 28220142 8 41 theme different 1421:1429 arg1 passages 1443:1450 different mouse brain passages 1421:1450 different mouse brain passages 1421:1450 Analysis of recombinant viruses containing amino acid substitutions selected at different mouse brain passages during the generation of Can revealed that altered Can GPC processing was primarily due to the T168A substitution within G1, which eliminates an N-linked glycosylation motif. 28220142 1 42 theme pathogenic 231:240 arg1 arenavirus 252:261 a highly pathogenic New World arenavirus 222:261 a highly pathogenic New World arenavirus 222:261 Junin virus (JUNV), a highly pathogenic New World arenavirus, is the causative agent of Argentine hemorrhagic fever (AHF). 28220142 1 42 theme pathogenic 231:240 arg1 virus 208:212 Junin virus 202:212 Junin virus (JUNV) 202:219 Junin virus (JUNV), a highly pathogenic New World arenavirus, is the causative agent of Argentine hemorrhagic fever (AHF). 28220142 12 43 theme Rom 2220:2222 arg1 GPC 2224:2226 Rom GPC 2220:2226 Rom GPC 2220:2226 Our results demonstrate that recombinant JUNV (rJUNV) expressing Can GPC display markedly different protein expression and elevated genomic RNA expression when compared to viruses expressing Rom GPC. 28220142 5 44 theme additional 836:845 arg1 vaccines 862:869 additional safe and novel vaccines 836:869 additional safe and novel vaccines 836:869 A more complete understanding of the mechanisms underlying the attenuation and immunogenicity of the Can strain will potentially allow for the rational design of additional safe and novel vaccines. 28220142 6 45 theme profiles 946:953 arg1 comparison 900:909 a detailed comparison 889:909 a detailed comparison of both RNA and protein expression profiles between both inter- and intra-segment chimeric JUNV recombinant clones expressing combinations of genes from the Can strain and the pathogenic Romero (Rom) strain 889:1116 Here, we provide a detailed comparison of both RNA and protein expression profiles between both inter- and intra-segment chimeric JUNV recombinant clones expressing combinations of genes from the Can strain and the pathogenic Romero (Rom) strain. 28220142 9 46 theme Can-like 1696:1703 arg1 pattern 1716:1722 a Can-like processing pattern 1694:1722 a Can-like processing pattern of Rom GPC 1694:1733 Incorporation of the T168A substitution in the Rom GPC resulted in a Can-like processing pattern of Rom GPC. 28220142 8 47 theme brain 1437:1441 arg1 passages 1443:1450 different mouse brain passages 1421:1450 different mouse brain passages 1421:1450 Analysis of recombinant viruses containing amino acid substitutions selected at different mouse brain passages during the generation of Can revealed that altered Can GPC processing was primarily due to the T168A substitution within G1, which eliminates an N-linked glycosylation motif. 28220142 4 48 theme the 643:645 arg1 attenuation 628:638 the attenuation 624:638 the attenuation of the Can strain 624:656 However, the mechanisms through which the GPC contributes to the attenuation of the Can strain remain unknown. 28220142 5 49 theme mechanisms 711:720 arg1 understanding 690:702 A more complete understanding 674:702 A more complete understanding of the mechanisms underlying the attenuation and immunogenicity of the Can strain 674:784 A more complete understanding of the mechanisms underlying the attenuation and immunogenicity of the Can strain will potentially allow for the rational design of additional safe and novel vaccines. 28220142 1 50 theme World 246:250 arg1 arenavirus 252:261 a highly pathogenic New World arenavirus 222:261 a highly pathogenic New World arenavirus 222:261 Junin virus (JUNV), a highly pathogenic New World arenavirus, is the causative agent of Argentine hemorrhagic fever (AHF). 28220142 1 50 theme World 246:250 arg1 virus 208:212 Junin virus 202:212 Junin virus (JUNV) 202:219 Junin virus (JUNV), a highly pathogenic New World arenavirus, is the causative agent of Argentine hemorrhagic fever (AHF). 28220142 8 51 link N-linked 1597:1604 arg1 motif 1620:1624 an N-linked glycosylation motif 1594:1624 an N-linked glycosylation motif 1594:1624 Analysis of recombinant viruses containing amino acid substitutions selected at different mouse brain passages during the generation of Can revealed that altered Can GPC processing was primarily due to the T168A substitution within G1, which eliminates an N-linked glycosylation motif. 28220142 6 52 theme protein 927:933 arg1 profiles 946:953 protein expression profiles 927:953 protein expression profiles 927:953 Here, we provide a detailed comparison of both RNA and protein expression profiles between both inter- and intra-segment chimeric JUNV recombinant clones expressing combinations of genes from the Can strain and the pathogenic Romero (Rom) strain. 28220142 5 53 dep the 771:773 arg1 Can 775:777 Can 775:777 Can 775:777 A more complete understanding of the mechanisms underlying the attenuation and immunogenicity of the Can strain will potentially allow for the rational design of additional safe and novel vaccines. 28220142 0 54 theme Glycosylation 23:35 arg1 Motif 37:41 an N-Linked Glycosylation Motif 11:41 an N-Linked Glycosylation Motif in the Glycoprotein of the Live-Attenuated Argentine Hemorrhagic Fever Vaccine 11:120 Absence of an N-Linked Glycosylation Motif in the Glycoprotein of the Live-Attenuated Argentine Hemorrhagic Fever Vaccine, Candid #1, Results in Its Improper Processing, and Reduced Surface Expression. 28220142 13 55 theme GPC 2451:2453 arg1 release 2455:2461 the GPC release 2447:2461 the GPC release from the ER 2447:2473 Additionally, our findings indicate that the N-linked glycosylation motif at amino acid positions 166-168 is important for trafficking of JUNV GPC to the cell surface, and the elimination of this motif interferes with the GPC release from the ER. 28220142 13 56 theme glycosylation 2283:2295 arg1 important 2338:2346 important 2338:2346 important 2338:2346 Additionally, our findings indicate that the N-linked glycosylation motif at amino acid positions 166-168 is important for trafficking of JUNV GPC to the cell surface, and the elimination of this motif interferes with the GPC release from the ER. 28220142 13 56 theme glycosylation 2283:2295 arg1 motif 2297:2301 the N-linked glycosylation motif 2270:2301 the N-linked glycosylation motif at amino acid positions 166-168 2270:2333 Additionally, our findings indicate that the N-linked glycosylation motif at amino acid positions 166-168 is important for trafficking of JUNV GPC to the cell surface, and the elimination of this motif interferes with the GPC release from the ER. 28220142 6 57 theme RNA 919:921 arg1 comparison 900:909 a detailed comparison 889:909 a detailed comparison of both RNA and protein expression profiles between both inter- and intra-segment chimeric JUNV recombinant clones expressing combinations of genes from the Can strain and the pathogenic Romero (Rom) strain 889:1116 Here, we provide a detailed comparison of both RNA and protein expression profiles between both inter- and intra-segment chimeric JUNV recombinant clones expressing combinations of genes from the Can strain and the pathogenic Romero (Rom) strain. 28220142 9 58 theme Rom 1727:1729 arg1 GPC 1731:1733 Rom GPC 1727:1733 Rom GPC 1727:1733 Incorporation of the T168A substitution in the Rom GPC resulted in a Can-like processing pattern of Rom GPC. 28220142 3 59 theme pig 545:547 arg1 model 549:553 a guinea pig model 536:553 a guinea pig model of AHF 536:560 We have previously shown that the Can glycoprotein (GPC) gene is the primary gene responsible for attenuation in a guinea pig model of AHF. 28220142 5 60 theme complete 681:688 arg1 understanding 690:702 A more complete understanding 674:702 A more complete understanding of the mechanisms underlying the attenuation and immunogenicity of the Can strain 674:784 A more complete understanding of the mechanisms underlying the attenuation and immunogenicity of the Can strain will potentially allow for the rational design of additional safe and novel vaccines. 28220142 5 61 dep attenuation 737:747 arg1 the 733:735 the 733:735 the 733:735 A more complete understanding of the mechanisms underlying the attenuation and immunogenicity of the Can strain will potentially allow for the rational design of additional safe and novel vaccines. 28220142 12 62 theme JUNV 2070:2073 arg1 expressing 2083:2092 recombinant JUNV (rJUNV) expressing 2058:2092 recombinant JUNV (rJUNV) expressing 2058:2092 Our results demonstrate that recombinant JUNV (rJUNV) expressing Can GPC display markedly different protein expression and elevated genomic RNA expression when compared to viruses expressing Rom GPC. 28220142 1 63 theme Junin 202:206 arg1 agent 281:285 the causative agent 267:285 the causative agent of Argentine hemorrhagic fever (AHF) 267:322 Junin virus (JUNV), a highly pathogenic New World arenavirus, is the causative agent of Argentine hemorrhagic fever (AHF). 28220142 1 63 theme Junin 202:206 arg1 JUNV 215:218 JUNV 215:218 JUNV 215:218 Junin virus (JUNV), a highly pathogenic New World arenavirus, is the causative agent of Argentine hemorrhagic fever (AHF). 28220142 1 63 theme Junin 202:206 arg1 virus 208:212 Junin virus 202:212 Junin virus (JUNV) 202:219 Junin virus (JUNV), a highly pathogenic New World arenavirus, is the causative agent of Argentine hemorrhagic fever (AHF). 28220142 1 63 theme Junin 202:206 arg1 arenavirus 252:261 a highly pathogenic New World arenavirus 222:261 a highly pathogenic New World arenavirus 222:261 Junin virus (JUNV), a highly pathogenic New World arenavirus, is the causative agent of Argentine hemorrhagic fever (AHF). 28220142 6 64 theme recombinant 1007:1017 arg1 clones 1019:1024 both inter- and intra-segment chimeric JUNV recombinant clones 963:1024 both inter- and intra-segment chimeric JUNV recombinant clones expressing combinations of genes from the Can strain and the pathogenic Romero (Rom) strain 963:1116 Here, we provide a detailed comparison of both RNA and protein expression profiles between both inter- and intra-segment chimeric JUNV recombinant clones expressing combinations of genes from the Can strain and the pathogenic Romero (Rom) strain. 28220142 10 65 theme JUNV 1749:1752 arg1 GPCs 1754:1757 JUNV GPCs 1749:1757 JUNV GPCs containing T168A substitution 1749:1787 In addition, JUNV GPCs containing T168A substitution were retained within the endoplasmic reticulum (ER) and displayed significantly lower cell surface expression than wild-type Rom GPC. 28220142 12 66 theme recombinant 2058:2068 arg1 expressing 2083:2092 recombinant JUNV (rJUNV) expressing 2058:2092 recombinant JUNV (rJUNV) expressing 2058:2092 Our results demonstrate that recombinant JUNV (rJUNV) expressing Can GPC display markedly different protein expression and elevated genomic RNA expression when compared to viruses expressing Rom GPC. 28220142 8 67 theme T168A 1547:1551 arg1 substitution 1553:1564 the T168A substitution 1543:1564 the T168A substitution within G1, which eliminates an N-linked glycosylation motif 1543:1624 Analysis of recombinant viruses containing amino acid substitutions selected at different mouse brain passages during the generation of Can revealed that altered Can GPC processing was primarily due to the T168A substitution within G1, which eliminates an N-linked glycosylation motif. 28220142 6 68 theme chimeric 993:1000 arg1 clones 1019:1024 both inter- and intra-segment chimeric JUNV recombinant clones 963:1024 both inter- and intra-segment chimeric JUNV recombinant clones expressing combinations of genes from the Can strain and the pathogenic Romero (Rom) strain 963:1116 Here, we provide a detailed comparison of both RNA and protein expression profiles between both inter- and intra-segment chimeric JUNV recombinant clones expressing combinations of genes from the Can strain and the pathogenic Romero (Rom) strain. 28220142 10 69 contain containing 1759:1768 arg1 GPCs 1754:1757 JUNV GPCs 1749:1757 JUNV GPCs containing T168A substitution 1749:1787 In addition, JUNV GPCs containing T168A substitution were retained within the endoplasmic reticulum (ER) and displayed significantly lower cell surface expression than wild-type Rom GPC. 28220142 10 69 contain containing 1759:1768 arg2 substitution 1776:1787 T168A substitution 1770:1787 T168A substitution 1770:1787 In addition, JUNV GPCs containing T168A substitution were retained within the endoplasmic reticulum (ER) and displayed significantly lower cell surface expression than wild-type Rom GPC. 28220142 3 70 theme glycoprotein 461:472 arg1 gene 480:483 glycoprotein (GPC) gene 461:483 glycoprotein (GPC) gene 461:483 We have previously shown that the Can glycoprotein (GPC) gene is the primary gene responsible for attenuation in a guinea pig model of AHF. 28220142 7 71 theme blot 1312:1315 arg1 analyses 1317:1324 Western blot analyses 1304:1324 Western blot analyses 1304:1324 The recombinant viruses that express Can GPC, which were shown to be attenuated in guinea pigs, displayed different RNA levels and GPC processing patterns as determined by Northern and Western blot analyses, respectively. 28220142 12 72 theme RNA 2169:2171 arg1 expression 2173:2182 elevated genomic RNA expression 2152:2182 elevated genomic RNA expression 2152:2182 Our results demonstrate that recombinant JUNV (rJUNV) expressing Can GPC display markedly different protein expression and elevated genomic RNA expression when compared to viruses expressing Rom GPC. 28220142 0 73 theme Surface 182:188 arg1 Expression 190:199 Reduced Surface Expression 174:199 Reduced Surface Expression 174:199 Absence of an N-Linked Glycosylation Motif in the Glycoprotein of the Live-Attenuated Argentine Hemorrhagic Fever Vaccine, Candid #1, Results in Its Improper Processing, and Reduced Surface Expression. 28220142 8 74 theme N-linked 1597:1604 arg1 motif 1620:1624 an N-linked glycosylation motif 1594:1624 an N-linked glycosylation motif 1594:1624 Analysis of recombinant viruses containing amino acid substitutions selected at different mouse brain passages during the generation of Can revealed that altered Can GPC processing was primarily due to the T168A substitution within G1, which eliminates an N-linked glycosylation motif. 28220142 5 75 theme the 771:773 arg1 attenuation 737:747 attenuation 737:747 attenuation 737:747 A more complete understanding of the mechanisms underlying the attenuation and immunogenicity of the Can strain will potentially allow for the rational design of additional safe and novel vaccines. 28220142 5 75 theme the 771:773 arg1 immunogenicity 753:766 immunogenicity 753:766 immunogenicity 753:766 A more complete understanding of the mechanisms underlying the attenuation and immunogenicity of the Can strain will potentially allow for the rational design of additional safe and novel vaccines. 28220142 11 76 from surface 2020:2026 arg1 GPC 1965:1967 GPC 1965:1967 GPC 1965:1967 Interestingly, the reversion A168T in Can GPC significantly increased GPC expression at the cell surface. 28220142 0 77 theme Candid 123:128 arg1 # 130:130 Candid #1 123:131 Candid #1 123:131 Absence of an N-Linked Glycosylation Motif in the Glycoprotein of the Live-Attenuated Argentine Hemorrhagic Fever Vaccine, Candid #1, Results in Its Improper Processing, and Reduced Surface Expression. 28220142 0 77 theme Candid 123:128 arg1 Absence 0:6 Absence 0:6 Absence of an N-Linked Glycosylation Motif in the Glycoprotein of the Live-Attenuated Argentine Hemorrhagic Fever Vaccine 0:120 Absence of an N-Linked Glycosylation Motif in the Glycoprotein of the Live-Attenuated Argentine Hemorrhagic Fever Vaccine, Candid #1, Results in Its Improper Processing, and Reduced Surface Expression. 28220142 3 78 theme GPC 475:477 arg1 gene 480:483 glycoprotein (GPC) gene 461:483 glycoprotein (GPC) gene 461:483 We have previously shown that the Can glycoprotein (GPC) gene is the primary gene responsible for attenuation in a guinea pig model of AHF. 28220142 11 79 theme reversion 1942:1950 arg1 A168T 1952:1956 the reversion A168T 1938:1956 the reversion A168T in 1938:1959 Interestingly, the reversion A168T in Can GPC significantly increased GPC expression at the cell surface. 28220142 8 80 contain containing 1373:1382 arg2 substitutions 1395:1407 amino acid substitutions 1384:1407 amino acid substitutions 1384:1407 Analysis of recombinant viruses containing amino acid substitutions selected at different mouse brain passages during the generation of Can revealed that altered Can GPC processing was primarily due to the T168A substitution within G1, which eliminates an N-linked glycosylation motif. 28220142 8 80 contain containing 1373:1382 arg1 viruses 1365:1371 recombinant viruses 1353:1371 recombinant viruses containing amino acid substitutions 1353:1407 Analysis of recombinant viruses containing amino acid substitutions selected at different mouse brain passages during the generation of Can revealed that altered Can GPC processing was primarily due to the T168A substitution within G1, which eliminates an N-linked glycosylation motif. 28220142 8 81 gly glycosylation 1606:1618 arg2 motif 1620:1624 an N-linked glycosylation motif 1594:1624 an N-linked glycosylation motif 1594:1624 Analysis of recombinant viruses containing amino acid substitutions selected at different mouse brain passages during the generation of Can revealed that altered Can GPC processing was primarily due to the T168A substitution within G1, which eliminates an N-linked glycosylation motif. 28220142 7 82 theme processing 1254:1263 arg1 patterns 1265:1272 GPC processing patterns 1250:1272 GPC processing patterns 1250:1272 The recombinant viruses that express Can GPC, which were shown to be attenuated in guinea pigs, displayed different RNA levels and GPC processing patterns as determined by Northern and Western blot analyses, respectively. 28220142 13 83 link N-linked 2274:2281 arg1 important 2338:2346 important 2338:2346 important 2338:2346 Additionally, our findings indicate that the N-linked glycosylation motif at amino acid positions 166-168 is important for trafficking of JUNV GPC to the cell surface, and the elimination of this motif interferes with the GPC release from the ER. 28220142 13 83 link N-linked 2274:2281 arg1 motif 2297:2301 the N-linked glycosylation motif 2270:2301 the N-linked glycosylation motif at amino acid positions 166-168 2270:2333 Additionally, our findings indicate that the N-linked glycosylation motif at amino acid positions 166-168 is important for trafficking of JUNV GPC to the cell surface, and the elimination of this motif interferes with the GPC release from the ER. 28220142 10 84 theme cell 1875:1878 arg1 expression 1888:1897 significantly lower cell surface expression 1855:1897 significantly lower cell surface expression 1855:1897 In addition, JUNV GPCs containing T168A substitution were retained within the endoplasmic reticulum (ER) and displayed significantly lower cell surface expression than wild-type Rom GPC. 28220142 4 85 dep the 643:645 arg1 Can 647:649 Can 647:649 Can 647:649 However, the mechanisms through which the GPC contributes to the attenuation of the Can strain remain unknown. 28220142 8 86 theme acid 1390:1393 arg1 substitutions 1395:1407 amino acid substitutions 1384:1407 amino acid substitutions 1384:1407 Analysis of recombinant viruses containing amino acid substitutions selected at different mouse brain passages during the generation of Can revealed that altered Can GPC processing was primarily due to the T168A substitution within G1, which eliminates an N-linked glycosylation motif. 28220142 11 87 theme increased 1983:1991 arg1 expression 1997:2006 significantly increased GPC expression 1969:2006 significantly increased GPC expression 1969:2006 Interestingly, the reversion A168T in Can GPC significantly increased GPC expression at the cell surface. 28220142 13 88 from positions 2317:2325 arg1 important 2338:2346 important 2338:2346 important 2338:2346 Additionally, our findings indicate that the N-linked glycosylation motif at amino acid positions 166-168 is important for trafficking of JUNV GPC to the cell surface, and the elimination of this motif interferes with the GPC release from the ER. 28220142 13 88 from positions 2317:2325 arg1 motif 2297:2301 the N-linked glycosylation motif 2270:2301 the N-linked glycosylation motif at amino acid positions 166-168 2270:2333 Additionally, our findings indicate that the N-linked glycosylation motif at amino acid positions 166-168 is important for trafficking of JUNV GPC to the cell surface, and the elimination of this motif interferes with the GPC release from the ER. 28220142 13 89 theme GPC 2372:2374 arg1 trafficking 2352:2362 trafficking 2352:2362 trafficking of JUNV GPC to the cell surface 2352:2394 Additionally, our findings indicate that the N-linked glycosylation motif at amino acid positions 166-168 is important for trafficking of JUNV GPC to the cell surface, and the elimination of this motif interferes with the GPC release from the ER. 28220142 5 90 theme rational 817:824 arg1 design 826:831 the rational design 813:831 the rational design of additional safe and novel vaccines 813:869 A more complete understanding of the mechanisms underlying the attenuation and immunogenicity of the Can strain will potentially allow for the rational design of additional safe and novel vaccines. 28220142 9 91 from Incorporation 1627:1639 arg1 GPC 1678:1680 the Rom GPC 1670:1680 the Rom GPC 1670:1680 Incorporation of the T168A substitution in the Rom GPC resulted in a Can-like processing pattern of Rom GPC. 28220142 8 92 theme viruses 1365:1371 arg1 Analysis 1341:1348 Analysis 1341:1348 Analysis of recombinant viruses containing amino acid substitutions 1341:1407 Analysis of recombinant viruses containing amino acid substitutions selected at different mouse brain passages during the generation of Can revealed that altered Can GPC processing was primarily due to the T168A substitution within G1, which eliminates an N-linked glycosylation motif. 28220142 7 93 theme RNA 1235:1237 arg1 levels 1239:1244 different RNA levels 1225:1244 different RNA levels 1225:1244 The recombinant viruses that express Can GPC, which were shown to be attenuated in guinea pigs, displayed different RNA levels and GPC processing patterns as determined by Northern and Western blot analyses, respectively. 28220142 10 94 theme wild-type 1904:1912 arg1 GPC 1918:1920 wild-type Rom GPC 1904:1920 wild-type Rom GPC 1904:1920 In addition, JUNV GPCs containing T168A substitution were retained within the endoplasmic reticulum (ER) and displayed significantly lower cell surface expression than wild-type Rom GPC. 28220142 9 95 theme T168A 1648:1652 arg1 substitution 1654:1665 the T168A substitution 1644:1665 the T168A substitution 1644:1665 Incorporation of the T168A substitution in the Rom GPC resulted in a Can-like processing pattern of Rom GPC. 28220142 8 96 theme amino 1384:1388 arg1 substitutions 1395:1407 amino acid substitutions 1384:1407 amino acid substitutions 1384:1407 Analysis of recombinant viruses containing amino acid substitutions selected at different mouse brain passages during the generation of Can revealed that altered Can GPC processing was primarily due to the T168A substitution within G1, which eliminates an N-linked glycosylation motif. 28220142 6 97 theme pathogenic 1087:1096 arg1 strain 1111:1116 the pathogenic Romero (Rom) strain 1083:1116 the pathogenic Romero (Rom) strain 1083:1116 Here, we provide a detailed comparison of both RNA and protein expression profiles between both inter- and intra-segment chimeric JUNV recombinant clones expressing combinations of genes from the Can strain and the pathogenic Romero (Rom) strain. 28220142 3 98 gly glycoprotein 461:472 arg1 glycoprotein 461:472 glycoprotein (GPC) gene 461:483 glycoprotein (GPC) gene 461:483 We have previously shown that the Can glycoprotein (GPC) gene is the primary gene responsible for attenuation in a guinea pig model of AHF. 28220142 0 99 theme Live-Attenuated 70:84 arg1 Fever 108:112 the Live-Attenuated Argentine Hemorrhagic Fever 66:112 the Live-Attenuated Argentine Hemorrhagic Fever Vaccine 66:120 Absence of an N-Linked Glycosylation Motif in the Glycoprotein of the Live-Attenuated Argentine Hemorrhagic Fever Vaccine, Candid #1, Results in Its Improper Processing, and Reduced Surface Expression. 28220142 2 100 theme at-risk 402:408 arg1 populations 410:420 at-risk populations 402:420 at-risk populations 402:420 The live-attenuated Candid #1 (Can) strain currently serves as a vaccine for at-risk populations. 28220142 0 101 theme Hemorrhagic 96:106 arg1 Fever 108:112 the Live-Attenuated Argentine Hemorrhagic Fever 66:112 the Live-Attenuated Argentine Hemorrhagic Fever Vaccine 66:120 Absence of an N-Linked Glycosylation Motif in the Glycoprotein of the Live-Attenuated Argentine Hemorrhagic Fever Vaccine, Candid #1, Results in Its Improper Processing, and Reduced Surface Expression. 28220142 1 102 theme hemorrhagic 300:310 arg1 AHF 319:321 AHF 319:321 AHF 319:321 Junin virus (JUNV), a highly pathogenic New World arenavirus, is the causative agent of Argentine hemorrhagic fever (AHF). 28220142 1 102 theme hemorrhagic 300:310 arg1 fever 312:316 Argentine hemorrhagic fever 290:316 Argentine hemorrhagic fever (AHF) 290:322 Junin virus (JUNV), a highly pathogenic New World arenavirus, is the causative agent of Argentine hemorrhagic fever (AHF). 28220142 5 103 theme novel 856:860 arg1 vaccines 862:869 additional safe and novel vaccines 836:869 additional safe and novel vaccines 836:869 A more complete understanding of the mechanisms underlying the attenuation and immunogenicity of the Can strain will potentially allow for the rational design of additional safe and novel vaccines. 28220142 9 104 theme Rom 1674:1676 arg1 GPC 1678:1680 the Rom GPC 1670:1680 the Rom GPC 1670:1680 Incorporation of the T168A substitution in the Rom GPC resulted in a Can-like processing pattern of Rom GPC. 28220142 12 105 theme elevated 2152:2159 arg1 expression 2173:2182 elevated genomic RNA expression 2152:2182 elevated genomic RNA expression 2152:2182 Our results demonstrate that recombinant JUNV (rJUNV) expressing Can GPC display markedly different protein expression and elevated genomic RNA expression when compared to viruses expressing Rom GPC. 28220142 0 106 theme Vaccine 114:120 arg1 Glycoprotein 50:61 the Glycoprotein 46:61 the Glycoprotein of the Live-Attenuated Argentine Hemorrhagic Fever Vaccine 46:120 Absence of an N-Linked Glycosylation Motif in the Glycoprotein of the Live-Attenuated Argentine Hemorrhagic Fever Vaccine, Candid #1, Results in Its Improper Processing, and Reduced Surface Expression. 28220142 7 107 theme guinea 1202:1207 arg1 pigs 1209:1212 guinea pigs 1202:1212 guinea pigs 1202:1212 The recombinant viruses that express Can GPC, which were shown to be attenuated in guinea pigs, displayed different RNA levels and GPC processing patterns as determined by Northern and Western blot analyses, respectively. 28220142 0 108 from Motif 37:41 arg1 Glycoprotein 50:61 the Glycoprotein 46:61 the Glycoprotein of the Live-Attenuated Argentine Hemorrhagic Fever Vaccine 46:120 Absence of an N-Linked Glycosylation Motif in the Glycoprotein of the Live-Attenuated Argentine Hemorrhagic Fever Vaccine, Candid #1, Results in Its Improper Processing, and Reduced Surface Expression. 28220142 12 109 theme protein 2129:2135 arg1 expression 2137:2146 markedly different protein expression 2110:2146 markedly different protein expression 2110:2146 Our results demonstrate that recombinant JUNV (rJUNV) expressing Can GPC display markedly different protein expression and elevated genomic RNA expression when compared to viruses expressing Rom GPC. 28220142 2 110 theme live-attenuated 329:343 arg1 vaccine 390:396 a vaccine 388:396 a vaccine for at-risk populations 388:420 The live-attenuated Candid #1 (Can) strain currently serves as a vaccine for at-risk populations. 28220142 2 110 theme live-attenuated 329:343 arg1 strain 361:366 The live-attenuated Candid #1 (Can) strain 325:366 The live-attenuated Candid #1 (Can) strain 325:366 The live-attenuated Candid #1 (Can) strain currently serves as a vaccine for at-risk populations. 28220142 13 111 theme amino 2306:2310 arg1 positions 2317:2325 amino acid positions 166-168 2306:2333 amino acid positions 166-168 2306:2333 Additionally, our findings indicate that the N-linked glycosylation motif at amino acid positions 166-168 is important for trafficking of JUNV GPC to the cell surface, and the elimination of this motif interferes with the GPC release from the ER. 28220142 0 112 theme N-Linked 14:21 arg1 Motif 37:41 an N-Linked Glycosylation Motif 11:41 an N-Linked Glycosylation Motif in the Glycoprotein of the Live-Attenuated Argentine Hemorrhagic Fever Vaccine 11:120 Absence of an N-Linked Glycosylation Motif in the Glycoprotein of the Live-Attenuated Argentine Hemorrhagic Fever Vaccine, Candid #1, Results in Its Improper Processing, and Reduced Surface Expression. 28220142 1 113 theme New 242:244 arg1 arenavirus 252:261 a highly pathogenic New World arenavirus 222:261 a highly pathogenic New World arenavirus 222:261 Junin virus (JUNV), a highly pathogenic New World arenavirus, is the causative agent of Argentine hemorrhagic fever (AHF). 28220142 1 113 theme New 242:244 arg1 virus 208:212 Junin virus 202:212 Junin virus (JUNV) 202:219 Junin virus (JUNV), a highly pathogenic New World arenavirus, is the causative agent of Argentine hemorrhagic fever (AHF). 28220142 5 114 theme safe 847:850 arg1 vaccines 862:869 additional safe and novel vaccines 836:869 additional safe and novel vaccines 836:869 A more complete understanding of the mechanisms underlying the attenuation and immunogenicity of the Can strain will potentially allow for the rational design of additional safe and novel vaccines. 28220142 6 115 theme expression 935:944 arg1 profiles 946:953 protein expression profiles 927:953 protein expression profiles 927:953 Here, we provide a detailed comparison of both RNA and protein expression profiles between both inter- and intra-segment chimeric JUNV recombinant clones expressing combinations of genes from the Can strain and the pathogenic Romero (Rom) strain. 28220142 9 116 theme processing 1705:1714 arg1 pattern 1716:1722 a Can-like processing pattern 1694:1722 a Can-like processing pattern of Rom GPC 1694:1733 Incorporation of the T168A substitution in the Rom GPC resulted in a Can-like processing pattern of Rom GPC. 28220142 0 117 theme Motif 37:41 arg1 # 130:130 Candid #1 123:131 Candid #1 123:131 Absence of an N-Linked Glycosylation Motif in the Glycoprotein of the Live-Attenuated Argentine Hemorrhagic Fever Vaccine, Candid #1, Results in Its Improper Processing, and Reduced Surface Expression. 28220142 0 117 theme Motif 37:41 arg1 Absence 0:6 Absence 0:6 Absence of an N-Linked Glycosylation Motif in the Glycoprotein of the Live-Attenuated Argentine Hemorrhagic Fever Vaccine 0:120 Absence of an N-Linked Glycosylation Motif in the Glycoprotein of the Live-Attenuated Argentine Hemorrhagic Fever Vaccine, Candid #1, Results in Its Improper Processing, and Reduced Surface Expression. 28220142 13 118 theme N-linked 2274:2281 arg1 important 2338:2346 important 2338:2346 important 2338:2346 Additionally, our findings indicate that the N-linked glycosylation motif at amino acid positions 166-168 is important for trafficking of JUNV GPC to the cell surface, and the elimination of this motif interferes with the GPC release from the ER. 28220142 13 118 theme N-linked 2274:2281 arg1 motif 2297:2301 the N-linked glycosylation motif 2270:2301 the N-linked glycosylation motif at amino acid positions 166-168 2270:2333 Additionally, our findings indicate that the N-linked glycosylation motif at amino acid positions 166-168 is important for trafficking of JUNV GPC to the cell surface, and the elimination of this motif interferes with the GPC release from the ER. 28220142 6 119 theme inter- 968:973 arg1 clones 1019:1024 both inter- and intra-segment chimeric JUNV recombinant clones 963:1024 both inter- and intra-segment chimeric JUNV recombinant clones expressing combinations of genes from the Can strain and the pathogenic Romero (Rom) strain 963:1116 Here, we provide a detailed comparison of both RNA and protein expression profiles between both inter- and intra-segment chimeric JUNV recombinant clones expressing combinations of genes from the Can strain and the pathogenic Romero (Rom) strain. 28220142 3 120 theme guinea 538:543 arg1 pig 545:547 guinea pig 538:547 a guinea pig model of AHF 536:560 We have previously shown that the Can glycoprotein (GPC) gene is the primary gene responsible for attenuation in a guinea pig model of AHF. 28220142 2 121 dep # 352:352 arg1 Can 356:358 Can 356:358 Can 356:358 The live-attenuated Candid #1 (Can) strain currently serves as a vaccine for at-risk populations. 28220142 2 122 theme # 352:352 arg1 vaccine 390:396 a vaccine 388:396 a vaccine for at-risk populations 388:420 The live-attenuated Candid #1 (Can) strain currently serves as a vaccine for at-risk populations. 28220142 2 122 theme # 352:352 arg1 strain 361:366 The live-attenuated Candid #1 (Can) strain 325:366 The live-attenuated Candid #1 (Can) strain 325:366 The live-attenuated Candid #1 (Can) strain currently serves as a vaccine for at-risk populations. 28220142 8 123 theme mouse 1431:1435 arg1 passages 1443:1450 different mouse brain passages 1421:1450 different mouse brain passages 1421:1450 Analysis of recombinant viruses containing amino acid substitutions selected at different mouse brain passages during the generation of Can revealed that altered Can GPC processing was primarily due to the T168A substitution within G1, which eliminates an N-linked glycosylation motif. 28220142 9 124 theme GPC 1731:1733 arg1 pattern 1716:1722 a Can-like processing pattern 1694:1722 a Can-like processing pattern of Rom GPC 1694:1733 Incorporation of the T168A substitution in the Rom GPC resulted in a Can-like processing pattern of Rom GPC. 28220142 10 125 theme T168A 1770:1774 arg1 substitution 1776:1787 T168A substitution 1770:1787 T168A substitution 1770:1787 In addition, JUNV GPCs containing T168A substitution were retained within the endoplasmic reticulum (ER) and displayed significantly lower cell surface expression than wild-type Rom GPC. 28220142 12 126 theme rJUNV 2076:2080 arg1 expressing 2083:2092 recombinant JUNV (rJUNV) expressing 2058:2092 recombinant JUNV (rJUNV) expressing 2058:2092 Our results demonstrate that recombinant JUNV (rJUNV) expressing Can GPC display markedly different protein expression and elevated genomic RNA expression when compared to viruses expressing Rom GPC. 28220142 1 127 theme causative 271:279 arg1 agent 281:285 the causative agent 267:285 the causative agent of Argentine hemorrhagic fever (AHF) 267:322 Junin virus (JUNV), a highly pathogenic New World arenavirus, is the causative agent of Argentine hemorrhagic fever (AHF). 28220142 1 127 theme causative 271:279 arg1 virus 208:212 Junin virus 202:212 Junin virus (JUNV) 202:219 Junin virus (JUNV), a highly pathogenic New World arenavirus, is the causative agent of Argentine hemorrhagic fever (AHF). 28220142 13 128 gly glycosylation 2283:2295 arg2 important 2338:2346 important 2338:2346 important 2338:2346 Additionally, our findings indicate that the N-linked glycosylation motif at amino acid positions 166-168 is important for trafficking of JUNV GPC to the cell surface, and the elimination of this motif interferes with the GPC release from the ER. 28220142 13 128 gly glycosylation 2283:2295 arg2 motif 2297:2301 the N-linked glycosylation motif 2270:2301 the N-linked glycosylation motif at amino acid positions 166-168 2270:2333 Additionally, our findings indicate that the N-linked glycosylation motif at amino acid positions 166-168 is important for trafficking of JUNV GPC to the cell surface, and the elimination of this motif interferes with the GPC release from the ER. 28220142 3 129 theme AHF 558:560 arg1 model 549:553 a guinea pig model 536:553 a guinea pig model of AHF 536:560 We have previously shown that the Can glycoprotein (GPC) gene is the primary gene responsible for attenuation in a guinea pig model of AHF. 28220142 6 130 theme JUNV 1002:1005 arg1 clones 1019:1024 both inter- and intra-segment chimeric JUNV recombinant clones 963:1024 both inter- and intra-segment chimeric JUNV recombinant clones expressing combinations of genes from the Can strain and the pathogenic Romero (Rom) strain 963:1116 Here, we provide a detailed comparison of both RNA and protein expression profiles between both inter- and intra-segment chimeric JUNV recombinant clones expressing combinations of genes from the Can strain and the pathogenic Romero (Rom) strain. 28220142 8 131 theme GPC 1507:1509 arg1 processing 1511:1520 GPC processing 1507:1520 GPC processing 1507:1520 Analysis of recombinant viruses containing amino acid substitutions selected at different mouse brain passages during the generation of Can revealed that altered Can GPC processing was primarily due to the T168A substitution within G1, which eliminates an N-linked glycosylation motif. 26269713 4 0 theme cellulolyticum 989:1002 arg1 dockerin 1015:1022 a R. cellulolyticum C-terminal dockerin 984:1022 a R. cellulolyticum C-terminal dockerin 984:1022 RESULTS The gene at locus Cphy_3367 encoding the major cellulase Cel9A from L. phytofermentans and an engineered gene coding for a modified enzyme harboring a R. cellulolyticum C-terminal dockerin were cloned in an expression vector. 26269713 8 1 theme cellulosomes 1748:1759 arg1 Analyses 1730:1737 Analyses 1730:1737 Analyses of their cellulosomes 1730:1759 Analyses of their cellulosomes showed that the engineered form of Cel9A bearing a dockerin was successfully incorporated in the complexes, but its integration induced an important release of regular cellulosomal components such as the major cellulase Cel48F, which severely impaired the activity of the complexes on cellulose. 26269713 3 2 theme cellulolytic 802:813 arg1 capacities 815:824 its cellulolytic capacities 798:824 its cellulolytic capacities 798:824 In the present study, the major cellulase from L. phytofermentans was introduced as a free enzyme or as a cellulosomal component in R. cellulolyticum to improve its cellulolytic capacities. 26269713 10 3 theme cellulolytic 2213:2224 arg1 strain 2226:2231 the most cellulolytic strain 2204:2231 the most cellulolytic strain secreting free Cel9A 2204:2252 Finally, the most cellulolytic strain secreting free Cel9A, was also characterized by an early production of lactate, acetate and ethanol as compared to the control strain. 26269713 3 4 from component 756:764 arg1 R. 769:770 R. 769:770 R. 769:770 In the present study, the major cellulase from L. phytofermentans was introduced as a free enzyme or as a cellulosomal component in R. cellulolyticum to improve its cellulolytic capacities. 26269713 6 5 theme cellulosomal 1404:1415 arg1 form 1417:1420 the cellulosomal form 1400:1420 the cellulosomal form of Cel9A 1400:1429 On minimal medium containing microcrystalline cellulose as the sole source of carbon, the strain secreting the free Cel9A started to grow sooner and consumed cellulose faster than the strain producing the cellulosomal form of Cel9A, or the control strain carrying an empty expression vector. 26269713 7 6 theme Cel9A 1589:1593 arg1 form 1581:1584 the cellulosomal form 1564:1584 the cellulosomal form of Cel9A 1564:1593 All strains reached the same final cell density but the strain producing the cellulosomal form of Cel9A was unable to completely consume the available cellulose even after an extended cultivation time, conversely to the two other strains. 26269713 6 7 theme free 1310:1313 arg1 Cel9A 1315:1319 the free Cel9A 1306:1319 the free Cel9A 1306:1319 On minimal medium containing microcrystalline cellulose as the sole source of carbon, the strain secreting the free Cel9A started to grow sooner and consumed cellulose faster than the strain producing the cellulosomal form of Cel9A, or the control strain carrying an empty expression vector. 26269713 7 8 theme final 1520:1524 arg1 density 1531:1537 the same final cell density 1511:1537 the same final cell density 1511:1537 All strains reached the same final cell density but the strain producing the cellulosomal form of Cel9A was unable to completely consume the available cellulose even after an extended cultivation time, conversely to the two other strains. 26269713 11 9 theme R. 2430:2431 arg1 cellulolyticum 2433:2446 R. cellulolyticum 2430:2446 R. cellulolyticum 2430:2446 CONCLUSIONS Our study shows that the cellulolytic capacity of R. cellulolyticum can be augmented by supplementing the cellulosomes with a free cellulase originating from L. phytofermentans, whereas integration of the heterologous enzyme in the cellulosomes is rather unfavorable. 26269713 8 10 theme complexes 2033:2041 arg1 activity 2017:2024 the activity 2013:2024 the activity of the complexes on cellulose 2013:2054 Analyses of their cellulosomes showed that the engineered form of Cel9A bearing a dockerin was successfully incorporated in the complexes, but its integration induced an important release of regular cellulosomal components such as the major cellulase Cel48F, which severely impaired the activity of the complexes on cellulose. 26269713 9 11 dep control 2106:2112 arg1 strains 2143:2149 Cel9A-secreting strains 2127:2149 Cel9A-secreting strains 2127:2149 In contrast, the cellulosomes synthesized by the control and the free Cel9A-secreting strains displayed similar composition and activity. 26269713 11 12 theme free 2506:2509 arg1 cellulase 2511:2519 a free cellulase 2504:2519 a free cellulase originating from L. phytofermentans 2504:2555 CONCLUSIONS Our study shows that the cellulolytic capacity of R. cellulolyticum can be augmented by supplementing the cellulosomes with a free cellulase originating from L. phytofermentans, whereas integration of the heterologous enzyme in the cellulosomes is rather unfavorable. 26269713 3 13 theme free 723:726 arg1 cellulase 669:677 the major cellulase 659:677 the major cellulase from L. phytofermentans 659:701 In the present study, the major cellulase from L. phytofermentans was introduced as a free enzyme or as a cellulosomal component in R. cellulolyticum to improve its cellulolytic capacities. 26269713 3 13 theme free 723:726 arg1 enzyme 728:733 a free enzyme 721:733 a free enzyme 721:733 In the present study, the major cellulase from L. phytofermentans was introduced as a free enzyme or as a cellulosomal component in R. cellulolyticum to improve its cellulolytic capacities. 26269713 10 14 theme lactate 2304:2310 arg1 production 2290:2299 an early production 2281:2299 an early production of lactate, acetate and ethanol 2281:2331 Finally, the most cellulolytic strain secreting free Cel9A, was also characterized by an early production of lactate, acetate and ethanol as compared to the control strain. 26269713 5 15 theme corresponding 1164:1176 arg1 strains 1190:1196 the corresponding recombinant strains 1160:1196 the corresponding recombinant strains 1160:1196 After electrotransformation of R. cellulolyticum, both forms of Cel9A were found to be secreted by the corresponding recombinant strains. 26269713 1 16 theme Lachnoclostridium 172:188 arg1 phytofermentans 190:204 Lachnoclostridium phytofermentans 172:204 Lachnoclostridium phytofermentans (formerly known as Clostridium cellulolyticum and Clostridium phytofermentans, respectively) 172:297 BACKGROUND Ruminiclostridium cellulolyticum and Lachnoclostridium phytofermentans (formerly known as Clostridium cellulolyticum and Clostridium phytofermentans, respectively) are anaerobic bacteria that developed different strategies to depolymerize the cellulose and the related plant cell wall polysaccharides. 26269713 1 16 theme Lachnoclostridium 172:188 arg1 BACKGROUND 124:133 BACKGROUND 124:133 BACKGROUND Ruminiclostridium cellulolyticum 124:166 BACKGROUND Ruminiclostridium cellulolyticum and Lachnoclostridium phytofermentans (formerly known as Clostridium cellulolyticum and Clostridium phytofermentans, respectively) are anaerobic bacteria that developed different strategies to depolymerize the cellulose and the related plant cell wall polysaccharides. 26269713 1 16 theme Lachnoclostridium 172:188 arg1 bacteria 313:320 anaerobic bacteria 303:320 anaerobic bacteria that developed different strategies to depolymerize the cellulose and the related plant cell wall polysaccharides 303:434 BACKGROUND Ruminiclostridium cellulolyticum and Lachnoclostridium phytofermentans (formerly known as Clostridium cellulolyticum and Clostridium phytofermentans, respectively) are anaerobic bacteria that developed different strategies to depolymerize the cellulose and the related plant cell wall polysaccharides. 26269713 5 17 theme R. 1092:1093 arg1 cellulolyticum 1095:1108 R. cellulolyticum 1092:1108 R. cellulolyticum 1092:1108 After electrotransformation of R. cellulolyticum, both forms of Cel9A were found to be secreted by the corresponding recombinant strains. 26269713 7 18 theme other 1715:1719 arg1 strains 1721:1727 the two other strains 1707:1727 the two other strains 1707:1727 All strains reached the same final cell density but the strain producing the cellulosomal form of Cel9A was unable to completely consume the available cellulose even after an extended cultivation time, conversely to the two other strains. 26269713 10 19 theme ethanol 2325:2331 arg1 production 2290:2299 an early production 2281:2299 an early production of lactate, acetate and ethanol 2281:2331 Finally, the most cellulolytic strain secreting free Cel9A, was also characterized by an early production of lactate, acetate and ethanol as compared to the control strain. 26269713 0 20 theme cellulosome-producing 58:78 arg1 bacterium 80:88 the cellulosome-producing bacterium Ruminiclostridium cellulolyticum 54:121 the cellulosome-producing bacterium Ruminiclostridium cellulolyticum 54:121 Combining free and aggregated cellulolytic systems in the cellulosome-producing bacterium Ruminiclostridium cellulolyticum. 26269713 8 21 theme regular 1921:1927 arg1 components 1942:1951 regular cellulosomal components 1921:1951 regular cellulosomal components such as the major cellulase Cel48F, which severely impaired the activity of the complexes on cellulose 1921:2054 Analyses of their cellulosomes showed that the engineered form of Cel9A bearing a dockerin was successfully incorporated in the complexes, but its integration induced an important release of regular cellulosomal components such as the major cellulase Cel48F, which severely impaired the activity of the complexes on cellulose. 26269713 8 21 theme regular 1921:1927 arg1 Cel48F 1981:1986 the major cellulase Cel48F 1961:1986 the major cellulase Cel48F 1961:1986 Analyses of their cellulosomes showed that the engineered form of Cel9A bearing a dockerin was successfully incorporated in the complexes, but its integration induced an important release of regular cellulosomal components such as the major cellulase Cel48F, which severely impaired the activity of the complexes on cellulose. 26269713 2 22 theme free 623:626 arg1 enzymes 628:634 free enzymes 623:634 free enzymes 623:634 Thus, R. cellulolyticum produces large extracellular multi-enzyme complexes termed cellulosomes, while L. phytofermentans secretes in the environment some cellulose-degrading enzymes as free enzymes. 26269713 10 23 theme acetate 2313:2319 arg1 production 2290:2299 an early production 2281:2299 an early production of lactate, acetate and ethanol 2281:2331 Finally, the most cellulolytic strain secreting free Cel9A, was also characterized by an early production of lactate, acetate and ethanol as compared to the control strain. 26269713 0 24 theme Ruminiclostridium 90:106 arg1 bacterium 80:88 the cellulosome-producing bacterium Ruminiclostridium cellulolyticum 54:121 the cellulosome-producing bacterium Ruminiclostridium cellulolyticum 54:121 Combining free and aggregated cellulolytic systems in the cellulosome-producing bacterium Ruminiclostridium cellulolyticum. 26269713 8 25 theme components 1942:1951 arg1 release 1910:1916 an important release 1897:1916 an important release of regular cellulosomal components such as the major cellulase Cel48F, which severely impaired the activity of the complexes on cellulose 1897:2054 Analyses of their cellulosomes showed that the engineered form of Cel9A bearing a dockerin was successfully incorporated in the complexes, but its integration induced an important release of regular cellulosomal components such as the major cellulase Cel48F, which severely impaired the activity of the complexes on cellulose. 26269713 6 26 contain containing 1217:1226 arg2 source 1267:1272 the sole source 1258:1272 the sole source of carbon 1258:1282 On minimal medium containing microcrystalline cellulose as the sole source of carbon, the strain secreting the free Cel9A started to grow sooner and consumed cellulose faster than the strain producing the cellulosomal form of Cel9A, or the control strain carrying an empty expression vector. 26269713 6 26 contain containing 1217:1226 arg1 medium 1210:1215 minimal medium 1202:1215 minimal medium containing microcrystalline cellulose as the sole source of carbon 1202:1282 On minimal medium containing microcrystalline cellulose as the sole source of carbon, the strain secreting the free Cel9A started to grow sooner and consumed cellulose faster than the strain producing the cellulosomal form of Cel9A, or the control strain carrying an empty expression vector. 26269713 6 26 contain containing 1217:1226 arg2 cellulose 1245:1253 microcrystalline cellulose 1228:1253 microcrystalline cellulose 1228:1253 On minimal medium containing microcrystalline cellulose as the sole source of carbon, the strain secreting the free Cel9A started to grow sooner and consumed cellulose faster than the strain producing the cellulosomal form of Cel9A, or the control strain carrying an empty expression vector. 26269713 1 27 dep phytofermentans 190:204 arg1 known 216:220 known 216:220 known as Clostridium cellulolyticum and Clostridium phytofermentans, respectively 216:296 BACKGROUND Ruminiclostridium cellulolyticum and Lachnoclostridium phytofermentans (formerly known as Clostridium cellulolyticum and Clostridium phytofermentans, respectively) are anaerobic bacteria that developed different strategies to depolymerize the cellulose and the related plant cell wall polysaccharides. 26269713 9 28 theme similar 2161:2167 arg1 composition 2169:2179 similar composition 2161:2179 similar composition 2161:2179 In contrast, the cellulosomes synthesized by the control and the free Cel9A-secreting strains displayed similar composition and activity. 26269713 6 29 theme expression 1472:1481 arg1 vector 1483:1488 an empty expression vector 1463:1488 an empty expression vector 1463:1488 On minimal medium containing microcrystalline cellulose as the sole source of carbon, the strain secreting the free Cel9A started to grow sooner and consumed cellulose faster than the strain producing the cellulosomal form of Cel9A, or the control strain carrying an empty expression vector. 26269713 8 30 theme major 1965:1969 arg1 Cel48F 1981:1986 the major cellulase Cel48F 1961:1986 the major cellulase Cel48F 1961:1986 Analyses of their cellulosomes showed that the engineered form of Cel9A bearing a dockerin was successfully incorporated in the complexes, but its integration induced an important release of regular cellulosomal components such as the major cellulase Cel48F, which severely impaired the activity of the complexes on cellulose. 26269713 2 31 theme multi-enzyme 490:501 arg1 complexes 503:511 large extracellular multi-enzyme complexes 470:511 large extracellular multi-enzyme complexes termed cellulosomes 470:531 Thus, R. cellulolyticum produces large extracellular multi-enzyme complexes termed cellulosomes, while L. phytofermentans secretes in the environment some cellulose-degrading enzymes as free enzymes. 26269713 4 32 theme major 876:880 arg1 Cel9A 892:896 the major cellulase Cel9A 872:896 the major cellulase Cel9A from L. phytofermentans 872:920 RESULTS The gene at locus Cphy_3367 encoding the major cellulase Cel9A from L. phytofermentans and an engineered gene coding for a modified enzyme harboring a R. cellulolyticum C-terminal dockerin were cloned in an expression vector. 26269713 5 33 theme cellulolyticum 1095:1108 arg1 electrotransformation 1067:1087 electrotransformation 1067:1087 electrotransformation of R. cellulolyticum 1067:1108 After electrotransformation of R. cellulolyticum, both forms of Cel9A were found to be secreted by the corresponding recombinant strains. 26269713 11 34 from integration 2566:2576 arg1 cellulosomes 2612:2623 the cellulosomes 2608:2623 the cellulosomes 2608:2623 CONCLUSIONS Our study shows that the cellulolytic capacity of R. cellulolyticum can be augmented by supplementing the cellulosomes with a free cellulase originating from L. phytofermentans, whereas integration of the heterologous enzyme in the cellulosomes is rather unfavorable. 26269713 0 35 theme cellulolytic 30:41 arg1 systems 43:49 free and aggregated cellulolytic systems 10:49 free and aggregated cellulolytic systems 10:49 Combining free and aggregated cellulolytic systems in the cellulosome-producing bacterium Ruminiclostridium cellulolyticum. 26269713 1 36 theme related 396:402 arg1 plant 404:408 the related plant 392:408 the related plant 392:408 BACKGROUND Ruminiclostridium cellulolyticum and Lachnoclostridium phytofermentans (formerly known as Clostridium cellulolyticum and Clostridium phytofermentans, respectively) are anaerobic bacteria that developed different strategies to depolymerize the cellulose and the related plant cell wall polysaccharides. 26269713 1 37 theme cell 410:413 arg1 polysaccharides 420:434 the cellulose and the related plant cell wall polysaccharides 374:434 the cellulose and the related plant cell wall polysaccharides 374:434 BACKGROUND Ruminiclostridium cellulolyticum and Lachnoclostridium phytofermentans (formerly known as Clostridium cellulolyticum and Clostridium phytofermentans, respectively) are anaerobic bacteria that developed different strategies to depolymerize the cellulose and the related plant cell wall polysaccharides. 26269713 7 38 theme available 1632:1640 arg1 cellulose 1642:1650 the available cellulose 1628:1650 the available cellulose 1628:1650 All strains reached the same final cell density but the strain producing the cellulosomal form of Cel9A was unable to completely consume the available cellulose even after an extended cultivation time, conversely to the two other strains. 26269713 11 39 dep CONCLUSIONS 2368:2378 arg1 shows 2390:2394 shows 2390:2394 shows that the cellulolytic capacity of R. cellulolyticum can be augmented by supplementing the cellulosomes with a free cellulase originating from L. phytofermentans, whereas integration of the heterologous enzyme in the cellulosomes is rather unfavorable 2390:2645 CONCLUSIONS Our study shows that the cellulolytic capacity of R. cellulolyticum can be augmented by supplementing the cellulosomes with a free cellulase originating from L. phytofermentans, whereas integration of the heterologous enzyme in the cellulosomes is rather unfavorable. 26269713 1 40 theme anaerobic 303:311 arg1 phytofermentans 190:204 Lachnoclostridium phytofermentans 172:204 Lachnoclostridium phytofermentans (formerly known as Clostridium cellulolyticum and Clostridium phytofermentans, respectively) 172:297 BACKGROUND Ruminiclostridium cellulolyticum and Lachnoclostridium phytofermentans (formerly known as Clostridium cellulolyticum and Clostridium phytofermentans, respectively) are anaerobic bacteria that developed different strategies to depolymerize the cellulose and the related plant cell wall polysaccharides. 26269713 1 40 theme anaerobic 303:311 arg1 BACKGROUND 124:133 BACKGROUND 124:133 BACKGROUND Ruminiclostridium cellulolyticum 124:166 BACKGROUND Ruminiclostridium cellulolyticum and Lachnoclostridium phytofermentans (formerly known as Clostridium cellulolyticum and Clostridium phytofermentans, respectively) are anaerobic bacteria that developed different strategies to depolymerize the cellulose and the related plant cell wall polysaccharides. 26269713 1 40 theme anaerobic 303:311 arg1 bacteria 313:320 anaerobic bacteria 303:320 anaerobic bacteria that developed different strategies to depolymerize the cellulose and the related plant cell wall polysaccharides 303:434 BACKGROUND Ruminiclostridium cellulolyticum and Lachnoclostridium phytofermentans (formerly known as Clostridium cellulolyticum and Clostridium phytofermentans, respectively) are anaerobic bacteria that developed different strategies to depolymerize the cellulose and the related plant cell wall polysaccharides. 26269713 6 41 theme sole 1262:1265 arg1 source 1267:1272 the sole source 1258:1272 the sole source of carbon 1258:1282 On minimal medium containing microcrystalline cellulose as the sole source of carbon, the strain secreting the free Cel9A started to grow sooner and consumed cellulose faster than the strain producing the cellulosomal form of Cel9A, or the control strain carrying an empty expression vector. 26269713 6 41 theme sole 1262:1265 arg1 cellulose 1245:1253 microcrystalline cellulose 1228:1253 microcrystalline cellulose 1228:1253 On minimal medium containing microcrystalline cellulose as the sole source of carbon, the strain secreting the free Cel9A started to grow sooner and consumed cellulose faster than the strain producing the cellulosomal form of Cel9A, or the control strain carrying an empty expression vector. 26269713 11 42 theme cellulolyticum 2433:2446 arg1 capacity 2418:2425 the cellulolytic capacity 2401:2425 the cellulolytic capacity of R. cellulolyticum 2401:2446 CONCLUSIONS Our study shows that the cellulolytic capacity of R. cellulolyticum can be augmented by supplementing the cellulosomes with a free cellulase originating from L. phytofermentans, whereas integration of the heterologous enzyme in the cellulosomes is rather unfavorable. 26269713 4 43 theme engineered 929:938 arg1 RESULTS 827:833 RESULTS The gene at locus Cphy_3367 encoding the major cellulase Cel9A from L. phytofermentans and an engineered gene coding for a modified enzyme harboring a R. cellulolyticum C-terminal dockerin 827:1022 RESULTS The gene at locus Cphy_3367 encoding the major cellulase Cel9A from L. phytofermentans and an engineered gene coding for a modified enzyme harboring a R. cellulolyticum C-terminal dockerin 827:1022 RESULTS The gene at locus Cphy_3367 encoding the major cellulase Cel9A from L. phytofermentans and an engineered gene coding for a modified enzyme harboring a R. cellulolyticum C-terminal dockerin were cloned in an expression vector. 26269713 4 43 theme engineered 929:938 arg1 gene 940:943 an engineered gene 926:943 an engineered gene coding for a modified enzyme harboring a R. cellulolyticum C-terminal dockerin 926:1022 RESULTS The gene at locus Cphy_3367 encoding the major cellulase Cel9A from L. phytofermentans and an engineered gene coding for a modified enzyme harboring a R. cellulolyticum C-terminal dockerin were cloned in an expression vector. 26269713 3 44 theme present 644:650 arg1 study 652:656 the present study 640:656 the present study 640:656 In the present study, the major cellulase from L. phytofermentans was introduced as a free enzyme or as a cellulosomal component in R. cellulolyticum to improve its cellulolytic capacities. 26269713 10 45 theme free 2243:2246 arg1 Cel9A 2248:2252 free Cel9A 2243:2252 free Cel9A 2243:2252 Finally, the most cellulolytic strain secreting free Cel9A, was also characterized by an early production of lactate, acetate and ethanol as compared to the control strain. 26269713 6 46 theme Cel9A 1425:1429 arg1 form 1417:1420 the cellulosomal form 1400:1420 the cellulosomal form of Cel9A 1400:1429 On minimal medium containing microcrystalline cellulose as the sole source of carbon, the strain secreting the free Cel9A started to grow sooner and consumed cellulose faster than the strain producing the cellulosomal form of Cel9A, or the control strain carrying an empty expression vector. 26269713 8 47 theme Cel9A 1796:1800 arg1 form 1788:1791 the engineered form 1773:1791 the engineered form of Cel9A bearing a dockerin 1773:1819 Analyses of their cellulosomes showed that the engineered form of Cel9A bearing a dockerin was successfully incorporated in the complexes, but its integration induced an important release of regular cellulosomal components such as the major cellulase Cel48F, which severely impaired the activity of the complexes on cellulose. 26269713 1 48 theme different 337:345 arg1 strategies 347:356 different strategies 337:356 different strategies 337:356 BACKGROUND Ruminiclostridium cellulolyticum and Lachnoclostridium phytofermentans (formerly known as Clostridium cellulolyticum and Clostridium phytofermentans, respectively) are anaerobic bacteria that developed different strategies to depolymerize the cellulose and the related plant cell wall polysaccharides. 26269713 4 49 theme R. 986:987 arg1 dockerin 1015:1022 a R. cellulolyticum C-terminal dockerin 984:1022 a R. cellulolyticum C-terminal dockerin 984:1022 RESULTS The gene at locus Cphy_3367 encoding the major cellulase Cel9A from L. phytofermentans and an engineered gene coding for a modified enzyme harboring a R. cellulolyticum C-terminal dockerin were cloned in an expression vector. 26269713 6 50 theme microcrystalline 1228:1243 arg1 source 1267:1272 the sole source 1258:1272 the sole source of carbon 1258:1282 On minimal medium containing microcrystalline cellulose as the sole source of carbon, the strain secreting the free Cel9A started to grow sooner and consumed cellulose faster than the strain producing the cellulosomal form of Cel9A, or the control strain carrying an empty expression vector. 26269713 6 50 theme microcrystalline 1228:1243 arg1 cellulose 1245:1253 microcrystalline cellulose 1228:1253 microcrystalline cellulose 1228:1253 On minimal medium containing microcrystalline cellulose as the sole source of carbon, the strain secreting the free Cel9A started to grow sooner and consumed cellulose faster than the strain producing the cellulosomal form of Cel9A, or the control strain carrying an empty expression vector. 26269713 3 51 theme major 663:667 arg1 cellulase 669:677 the major cellulase 659:677 the major cellulase from L. phytofermentans 659:701 In the present study, the major cellulase from L. phytofermentans was introduced as a free enzyme or as a cellulosomal component in R. cellulolyticum to improve its cellulolytic capacities. 26269713 3 51 theme major 663:667 arg1 component 756:764 a cellulosomal component 741:764 a cellulosomal component in R. cellulolyticum to improve its cellulolytic capacities 741:824 In the present study, the major cellulase from L. phytofermentans was introduced as a free enzyme or as a cellulosomal component in R. cellulolyticum to improve its cellulolytic capacities. 26269713 3 51 theme major 663:667 arg1 enzyme 728:733 a free enzyme 721:733 a free enzyme 721:733 In the present study, the major cellulase from L. phytofermentans was introduced as a free enzyme or as a cellulosomal component in R. cellulolyticum to improve its cellulolytic capacities. 26269713 11 52 theme heterologous 2585:2596 arg1 enzyme 2598:2603 the heterologous enzyme 2581:2603 the heterologous enzyme 2581:2603 CONCLUSIONS Our study shows that the cellulolytic capacity of R. cellulolyticum can be augmented by supplementing the cellulosomes with a free cellulase originating from L. phytofermentans, whereas integration of the heterologous enzyme in the cellulosomes is rather unfavorable. 26269713 4 53 theme C-terminal 1004:1013 arg1 dockerin 1015:1022 a R. cellulolyticum C-terminal dockerin 984:1022 a R. cellulolyticum C-terminal dockerin 984:1022 RESULTS The gene at locus Cphy_3367 encoding the major cellulase Cel9A from L. phytofermentans and an engineered gene coding for a modified enzyme harboring a R. cellulolyticum C-terminal dockerin were cloned in an expression vector. 26269713 11 54 dep augmented 2455:2463 arg1 whereas 2558:2564 whereas 2558:2564 whereas 2558:2564 CONCLUSIONS Our study shows that the cellulolytic capacity of R. cellulolyticum can be augmented by supplementing the cellulosomes with a free cellulase originating from L. phytofermentans, whereas integration of the heterologous enzyme in the cellulosomes is rather unfavorable. 26269713 7 55 theme cellulosomal 1568:1579 arg1 form 1581:1584 the cellulosomal form 1564:1584 the cellulosomal form of Cel9A 1564:1593 All strains reached the same final cell density but the strain producing the cellulosomal form of Cel9A was unable to completely consume the available cellulose even after an extended cultivation time, conversely to the two other strains. 26269713 4 56 theme modified 958:965 arg1 enzyme 967:972 a modified enzyme 956:972 a modified enzyme harboring a R. cellulolyticum C-terminal dockerin 956:1022 RESULTS The gene at locus Cphy_3367 encoding the major cellulase Cel9A from L. phytofermentans and an engineered gene coding for a modified enzyme harboring a R. cellulolyticum C-terminal dockerin were cloned in an expression vector. 26269713 10 57 theme early 2284:2288 arg1 production 2290:2299 an early production 2281:2299 an early production of lactate, acetate and ethanol 2281:2331 Finally, the most cellulolytic strain secreting free Cel9A, was also characterized by an early production of lactate, acetate and ethanol as compared to the control strain. 26269713 6 58 theme empty 1466:1470 arg1 vector 1483:1488 an empty expression vector 1463:1488 an empty expression vector 1463:1488 On minimal medium containing microcrystalline cellulose as the sole source of carbon, the strain secreting the free Cel9A started to grow sooner and consumed cellulose faster than the strain producing the cellulosomal form of Cel9A, or the control strain carrying an empty expression vector. 26269713 10 59 theme control 2352:2358 arg1 strain 2360:2365 the control strain 2348:2365 the control strain 2348:2365 Finally, the most cellulolytic strain secreting free Cel9A, was also characterized by an early production of lactate, acetate and ethanol as compared to the control strain. 26269713 4 60 theme expression 1042:1051 arg1 vector 1053:1058 an expression vector 1039:1058 an expression vector 1039:1058 RESULTS The gene at locus Cphy_3367 encoding the major cellulase Cel9A from L. phytofermentans and an engineered gene coding for a modified enzyme harboring a R. cellulolyticum C-terminal dockerin were cloned in an expression vector. 26269713 7 61 theme cell 1526:1529 arg1 density 1531:1537 the same final cell density 1511:1537 the same final cell density 1511:1537 All strains reached the same final cell density but the strain producing the cellulosomal form of Cel9A was unable to completely consume the available cellulose even after an extended cultivation time, conversely to the two other strains. 26269713 11 62 theme cellulolytic 2405:2416 arg1 capacity 2418:2425 the cellulolytic capacity 2401:2425 the cellulolytic capacity of R. cellulolyticum 2401:2446 CONCLUSIONS Our study shows that the cellulolytic capacity of R. cellulolyticum can be augmented by supplementing the cellulosomes with a free cellulase originating from L. phytofermentans, whereas integration of the heterologous enzyme in the cellulosomes is rather unfavorable. 26269713 4 63 from locus 847:851 arg1 gene 839:842 The gene 835:842 The gene at locus Cphy_3367 encoding the major cellulase Cel9A from L. phytofermentans 835:920 RESULTS The gene at locus Cphy_3367 encoding the major cellulase Cel9A from L. phytofermentans and an engineered gene coding for a modified enzyme harboring a R. cellulolyticum C-terminal dockerin were cloned in an expression vector. 26269713 4 63 from locus 847:851 arg1 RESULTS 827:833 RESULTS The gene at locus Cphy_3367 encoding the major cellulase Cel9A from L. phytofermentans and an engineered gene coding for a modified enzyme harboring a R. cellulolyticum C-terminal dockerin 827:1022 RESULTS The gene at locus Cphy_3367 encoding the major cellulase Cel9A from L. phytofermentans and an engineered gene coding for a modified enzyme harboring a R. cellulolyticum C-terminal dockerin 827:1022 RESULTS The gene at locus Cphy_3367 encoding the major cellulase Cel9A from L. phytofermentans and an engineered gene coding for a modified enzyme harboring a R. cellulolyticum C-terminal dockerin were cloned in an expression vector. 26269713 4 63 from locus 847:851 arg1 gene 940:943 an engineered gene 926:943 an engineered gene coding for a modified enzyme harboring a R. cellulolyticum C-terminal dockerin 926:1022 RESULTS The gene at locus Cphy_3367 encoding the major cellulase Cel9A from L. phytofermentans and an engineered gene coding for a modified enzyme harboring a R. cellulolyticum C-terminal dockerin were cloned in an expression vector. 26269713 7 64 theme same 1515:1518 arg1 density 1531:1537 the same final cell density 1511:1537 the same final cell density 1511:1537 All strains reached the same final cell density but the strain producing the cellulosomal form of Cel9A was unable to completely consume the available cellulose even after an extended cultivation time, conversely to the two other strains. 26269713 6 65 theme control 1439:1445 arg1 strain 1447:1452 the control strain 1435:1452 the control strain carrying an empty expression vector 1435:1488 On minimal medium containing microcrystalline cellulose as the sole source of carbon, the strain secreting the free Cel9A started to grow sooner and consumed cellulose faster than the strain producing the cellulosomal form of Cel9A, or the control strain carrying an empty expression vector. 26269713 5 66 theme recombinant 1178:1188 arg1 strains 1190:1196 the corresponding recombinant strains 1160:1196 the corresponding recombinant strains 1160:1196 After electrotransformation of R. cellulolyticum, both forms of Cel9A were found to be secreted by the corresponding recombinant strains. 26269713 6 67 contain carrying 1454:1461 arg2 vector 1483:1488 an empty expression vector 1463:1488 an empty expression vector 1463:1488 On minimal medium containing microcrystalline cellulose as the sole source of carbon, the strain secreting the free Cel9A started to grow sooner and consumed cellulose faster than the strain producing the cellulosomal form of Cel9A, or the control strain carrying an empty expression vector. 26269713 6 67 contain carrying 1454:1461 arg1 strain 1447:1452 the control strain 1435:1452 the control strain carrying an empty expression vector 1435:1488 On minimal medium containing microcrystalline cellulose as the sole source of carbon, the strain secreting the free Cel9A started to grow sooner and consumed cellulose faster than the strain producing the cellulosomal form of Cel9A, or the control strain carrying an empty expression vector. 26269713 11 68 theme enzyme 2598:2603 arg1 integration 2566:2576 integration 2566:2576 integration of the heterologous enzyme in the cellulosomes 2566:2623 CONCLUSIONS Our study shows that the cellulolytic capacity of R. cellulolyticum can be augmented by supplementing the cellulosomes with a free cellulase originating from L. phytofermentans, whereas integration of the heterologous enzyme in the cellulosomes is rather unfavorable. 26269713 3 69 from phytofermentans 687:701 arg1 cellulase 669:677 the major cellulase 659:677 the major cellulase from L. phytofermentans 659:701 In the present study, the major cellulase from L. phytofermentans was introduced as a free enzyme or as a cellulosomal component in R. cellulolyticum to improve its cellulolytic capacities. 26269713 3 69 from phytofermentans 687:701 arg1 component 756:764 a cellulosomal component 741:764 a cellulosomal component in R. cellulolyticum to improve its cellulolytic capacities 741:824 In the present study, the major cellulase from L. phytofermentans was introduced as a free enzyme or as a cellulosomal component in R. cellulolyticum to improve its cellulolytic capacities. 26269713 3 69 from phytofermentans 687:701 arg1 enzyme 728:733 a free enzyme 721:733 a free enzyme 721:733 In the present study, the major cellulase from L. phytofermentans was introduced as a free enzyme or as a cellulosomal component in R. cellulolyticum to improve its cellulolytic capacities. 26269713 8 70 theme important 1900:1908 arg1 release 1910:1916 an important release 1897:1916 an important release of regular cellulosomal components such as the major cellulase Cel48F, which severely impaired the activity of the complexes on cellulose 1897:2054 Analyses of their cellulosomes showed that the engineered form of Cel9A bearing a dockerin was successfully incorporated in the complexes, but its integration induced an important release of regular cellulosomal components such as the major cellulase Cel48F, which severely impaired the activity of the complexes on cellulose. 26269713 4 71 from phytofermentans 906:920 arg1 Cel9A 892:896 the major cellulase Cel9A 872:896 the major cellulase Cel9A from L. phytofermentans 872:920 RESULTS The gene at locus Cphy_3367 encoding the major cellulase Cel9A from L. phytofermentans and an engineered gene coding for a modified enzyme harboring a R. cellulolyticum C-terminal dockerin were cloned in an expression vector. 26269713 9 72 theme Cel9A-secreting 2127:2141 arg1 strains 2143:2149 Cel9A-secreting strains 2127:2149 Cel9A-secreting strains 2127:2149 In contrast, the cellulosomes synthesized by the control and the free Cel9A-secreting strains displayed similar composition and activity. 26269713 8 73 theme cellulosomal 1929:1940 arg1 components 1942:1951 regular cellulosomal components 1921:1951 regular cellulosomal components such as the major cellulase Cel48F, which severely impaired the activity of the complexes on cellulose 1921:2054 Analyses of their cellulosomes showed that the engineered form of Cel9A bearing a dockerin was successfully incorporated in the complexes, but its integration induced an important release of regular cellulosomal components such as the major cellulase Cel48F, which severely impaired the activity of the complexes on cellulose. 26269713 8 73 theme cellulosomal 1929:1940 arg1 Cel48F 1981:1986 the major cellulase Cel48F 1961:1986 the major cellulase Cel48F 1961:1986 Analyses of their cellulosomes showed that the engineered form of Cel9A bearing a dockerin was successfully incorporated in the complexes, but its integration induced an important release of regular cellulosomal components such as the major cellulase Cel48F, which severely impaired the activity of the complexes on cellulose. 26269713 4 74 dep RESULTS 827:833 arg1 gene 839:842 The gene 835:842 The gene at locus Cphy_3367 encoding the major cellulase Cel9A from L. phytofermentans 835:920 RESULTS The gene at locus Cphy_3367 encoding the major cellulase Cel9A from L. phytofermentans and an engineered gene coding for a modified enzyme harboring a R. cellulolyticum C-terminal dockerin were cloned in an expression vector. 26269713 4 74 dep RESULTS 827:833 arg1 RESULTS 827:833 RESULTS The gene at locus Cphy_3367 encoding the major cellulase Cel9A from L. phytofermentans and an engineered gene coding for a modified enzyme harboring a R. cellulolyticum C-terminal dockerin 827:1022 RESULTS The gene at locus Cphy_3367 encoding the major cellulase Cel9A from L. phytofermentans and an engineered gene coding for a modified enzyme harboring a R. cellulolyticum C-terminal dockerin 827:1022 RESULTS The gene at locus Cphy_3367 encoding the major cellulase Cel9A from L. phytofermentans and an engineered gene coding for a modified enzyme harboring a R. cellulolyticum C-terminal dockerin were cloned in an expression vector. 26269713 4 74 dep RESULTS 827:833 arg1 gene 940:943 an engineered gene 926:943 an engineered gene coding for a modified enzyme harboring a R. cellulolyticum C-terminal dockerin 926:1022 RESULTS The gene at locus Cphy_3367 encoding the major cellulase Cel9A from L. phytofermentans and an engineered gene coding for a modified enzyme harboring a R. cellulolyticum C-terminal dockerin were cloned in an expression vector. 26269713 7 75 theme cultivation 1675:1685 arg1 time 1687:1690 an extended cultivation time 1663:1690 an extended cultivation time 1663:1690 All strains reached the same final cell density but the strain producing the cellulosomal form of Cel9A was unable to completely consume the available cellulose even after an extended cultivation time, conversely to the two other strains. 26269713 2 76 dep R. 443:444 arg1 cellulolyticum 446:459 R. cellulolyticum 443:459 R. cellulolyticum 443:459 Thus, R. cellulolyticum produces large extracellular multi-enzyme complexes termed cellulosomes, while L. phytofermentans secretes in the environment some cellulose-degrading enzymes as free enzymes. 26269713 4 77 theme cellulase 882:890 arg1 Cel9A 892:896 the major cellulase Cel9A 872:896 the major cellulase Cel9A from L. phytofermentans 872:920 RESULTS The gene at locus Cphy_3367 encoding the major cellulase Cel9A from L. phytofermentans and an engineered gene coding for a modified enzyme harboring a R. cellulolyticum C-terminal dockerin were cloned in an expression vector. 26269713 0 78 theme free 10:13 arg1 systems 43:49 free and aggregated cellulolytic systems 10:49 free and aggregated cellulolytic systems 10:49 Combining free and aggregated cellulolytic systems in the cellulosome-producing bacterium Ruminiclostridium cellulolyticum. 26269713 6 79 theme minimal 1202:1208 arg1 medium 1210:1215 minimal medium 1202:1215 minimal medium containing microcrystalline cellulose as the sole source of carbon 1202:1282 On minimal medium containing microcrystalline cellulose as the sole source of carbon, the strain secreting the free Cel9A started to grow sooner and consumed cellulose faster than the strain producing the cellulosomal form of Cel9A, or the control strain carrying an empty expression vector. 26269713 1 80 dep Clostridium 225:235 arg1 cellulolyticum 237:250 cellulolyticum 237:250 cellulolyticum 237:250 BACKGROUND Ruminiclostridium cellulolyticum and Lachnoclostridium phytofermentans (formerly known as Clostridium cellulolyticum and Clostridium phytofermentans, respectively) are anaerobic bacteria that developed different strategies to depolymerize the cellulose and the related plant cell wall polysaccharides. 26269713 2 81 theme extracellular 476:488 arg1 complexes 503:511 large extracellular multi-enzyme complexes 470:511 large extracellular multi-enzyme complexes termed cellulosomes 470:531 Thus, R. cellulolyticum produces large extracellular multi-enzyme complexes termed cellulosomes, while L. phytofermentans secretes in the environment some cellulose-degrading enzymes as free enzymes. 26269713 0 82 theme aggregated 19:28 arg1 systems 43:49 free and aggregated cellulolytic systems 10:49 free and aggregated cellulolytic systems 10:49 Combining free and aggregated cellulolytic systems in the cellulosome-producing bacterium Ruminiclostridium cellulolyticum. 26269713 1 83 theme cellulose 378:386 arg1 polysaccharides 420:434 the cellulose and the related plant cell wall polysaccharides 374:434 the cellulose and the related plant cell wall polysaccharides 374:434 BACKGROUND Ruminiclostridium cellulolyticum and Lachnoclostridium phytofermentans (formerly known as Clostridium cellulolyticum and Clostridium phytofermentans, respectively) are anaerobic bacteria that developed different strategies to depolymerize the cellulose and the related plant cell wall polysaccharides. 26269713 8 84 theme cellulase 1971:1979 arg1 Cel48F 1981:1986 the major cellulase Cel48F 1961:1986 the major cellulase Cel48F 1961:1986 Analyses of their cellulosomes showed that the engineered form of Cel9A bearing a dockerin was successfully incorporated in the complexes, but its integration induced an important release of regular cellulosomal components such as the major cellulase Cel48F, which severely impaired the activity of the complexes on cellulose. 26269713 0 85 dep bacterium 80:88 arg1 cellulolyticum 108:121 the cellulosome-producing bacterium Ruminiclostridium cellulolyticum 54:121 the cellulosome-producing bacterium Ruminiclostridium cellulolyticum 54:121 Combining free and aggregated cellulolytic systems in the cellulosome-producing bacterium Ruminiclostridium cellulolyticum. 26269713 1 86 dep known 216:220 arg1 formerly 207:214 formerly 207:214 formerly 207:214 BACKGROUND Ruminiclostridium cellulolyticum and Lachnoclostridium phytofermentans (formerly known as Clostridium cellulolyticum and Clostridium phytofermentans, respectively) are anaerobic bacteria that developed different strategies to depolymerize the cellulose and the related plant cell wall polysaccharides. 26269713 2 87 theme large 470:474 arg1 complexes 503:511 large extracellular multi-enzyme complexes 470:511 large extracellular multi-enzyme complexes termed cellulosomes 470:531 Thus, R. cellulolyticum produces large extracellular multi-enzyme complexes termed cellulosomes, while L. phytofermentans secretes in the environment some cellulose-degrading enzymes as free enzymes. 26269713 7 88 theme extended 1666:1673 arg1 time 1687:1690 an extended cultivation time 1663:1690 an extended cultivation time 1663:1690 All strains reached the same final cell density but the strain producing the cellulosomal form of Cel9A was unable to completely consume the available cellulose even after an extended cultivation time, conversely to the two other strains. 26269713 2 89 theme cellulose-degrading 592:610 arg1 enzymes 612:618 some cellulose-degrading enzymes 587:618 some cellulose-degrading enzymes as free enzymes 587:634 Thus, R. cellulolyticum produces large extracellular multi-enzyme complexes termed cellulosomes, while L. phytofermentans secretes in the environment some cellulose-degrading enzymes as free enzymes. 26269713 3 90 theme cellulosomal 743:754 arg1 cellulase 669:677 the major cellulase 659:677 the major cellulase from L. phytofermentans 659:701 In the present study, the major cellulase from L. phytofermentans was introduced as a free enzyme or as a cellulosomal component in R. cellulolyticum to improve its cellulolytic capacities. 26269713 3 90 theme cellulosomal 743:754 arg1 component 756:764 a cellulosomal component 741:764 a cellulosomal component in R. cellulolyticum to improve its cellulolytic capacities 741:824 In the present study, the major cellulase from L. phytofermentans was introduced as a free enzyme or as a cellulosomal component in R. cellulolyticum to improve its cellulolytic capacities. 26269713 1 91 theme plant 404:408 arg1 polysaccharides 420:434 the cellulose and the related plant cell wall polysaccharides 374:434 the cellulose and the related plant cell wall polysaccharides 374:434 BACKGROUND Ruminiclostridium cellulolyticum and Lachnoclostridium phytofermentans (formerly known as Clostridium cellulolyticum and Clostridium phytofermentans, respectively) are anaerobic bacteria that developed different strategies to depolymerize the cellulose and the related plant cell wall polysaccharides. 26269713 6 92 theme carbon 1277:1282 arg1 source 1267:1272 the sole source 1258:1272 the sole source of carbon 1258:1282 On minimal medium containing microcrystalline cellulose as the sole source of carbon, the strain secreting the free Cel9A started to grow sooner and consumed cellulose faster than the strain producing the cellulosomal form of Cel9A, or the control strain carrying an empty expression vector. 26269713 6 92 theme carbon 1277:1282 arg1 cellulose 1245:1253 microcrystalline cellulose 1228:1253 microcrystalline cellulose 1228:1253 On minimal medium containing microcrystalline cellulose as the sole source of carbon, the strain secreting the free Cel9A started to grow sooner and consumed cellulose faster than the strain producing the cellulosomal form of Cel9A, or the control strain carrying an empty expression vector. 26269713 8 93 from activity 2017:2024 arg1 cellulose 2046:2054 cellulose 2046:2054 cellulose 2046:2054 Analyses of their cellulosomes showed that the engineered form of Cel9A bearing a dockerin was successfully incorporated in the complexes, but its integration induced an important release of regular cellulosomal components such as the major cellulase Cel48F, which severely impaired the activity of the complexes on cellulose. 26269713 8 94 theme engineered 1777:1786 arg1 form 1788:1791 the engineered form 1773:1791 the engineered form of Cel9A bearing a dockerin 1773:1819 Analyses of their cellulosomes showed that the engineered form of Cel9A bearing a dockerin was successfully incorporated in the complexes, but its integration induced an important release of regular cellulosomal components such as the major cellulase Cel48F, which severely impaired the activity of the complexes on cellulose. 26269713 1 95 theme wall 415:418 arg1 polysaccharides 420:434 the cellulose and the related plant cell wall polysaccharides 374:434 the cellulose and the related plant cell wall polysaccharides 374:434 BACKGROUND Ruminiclostridium cellulolyticum and Lachnoclostridium phytofermentans (formerly known as Clostridium cellulolyticum and Clostridium phytofermentans, respectively) are anaerobic bacteria that developed different strategies to depolymerize the cellulose and the related plant cell wall polysaccharides. 26269713 5 96 theme Cel9A 1125:1129 arg1 forms 1116:1120 both forms 1111:1120 both forms of Cel9A 1111:1129 After electrotransformation of R. cellulolyticum, both forms of Cel9A were found to be secreted by the corresponding recombinant strains. 26269713 6 97 theme faster 1367:1372 arg1 cellulose 1357:1365 cellulose 1357:1365 cellulose faster than the strain producing the cellulosomal form of Cel9A, or the control strain carrying an empty expression vector 1357:1488 On minimal medium containing microcrystalline cellulose as the sole source of carbon, the strain secreting the free Cel9A started to grow sooner and consumed cellulose faster than the strain producing the cellulosomal form of Cel9A, or the control strain carrying an empty expression vector. 26269713 3 98 dep R. 769:770 arg1 cellulolyticum 772:785 R. cellulolyticum to improve its cellulolytic capacities 769:824 R. cellulolyticum to improve its cellulolytic capacities 769:824 In the present study, the major cellulase from L. phytofermentans was introduced as a free enzyme or as a cellulosomal component in R. cellulolyticum to improve its cellulolytic capacities. 24388829 0 0 theme matter 77:82 arg1 character 20:28 the character 16:28 the character of algal extracellular versus cellular organic matter 16:82 A comparison of the character of algal extracellular versus cellular organic matter produced by cyanobacterium, diatom and green alga. 24388829 1 1 dep crotonensis 290:300 arg1 geitleri 331:338 Chlamydomonas geitleri 317:338 Chlamydomonas geitleri 317:338 This study investigated characteristics of algal organic matter (AOM) derived from three species (cyanobacterium Microcystis aeruginosa, diatom Fragilaria crotonensis and green alga Chlamydomonas geitleri) which dominate phytoplanktonic populations in reservoirs supplying drinking water treatment plants. 24388829 9 2 theme AOM 1599:1601 arg1 water 1609:1613 AOM laden water 1599:1613 AOM laden water 1599:1613 The results imply that the knowledge of AOM composition and characteristics predetermine which processes would be effective in the treatment of AOM laden water. 24388829 8 3 with peptides/proteins 1350:1366 arg1 portion 1387:1393 a significant portion 1373:1393 a significant portion of high-MW ones (22%) 1373:1415 The highest amount of peptides/proteins with a significant portion of high-MW ones (22%) was observed in COM of M. aeruginosa. 24388829 0 4 theme organic 69:75 arg1 matter 77:82 algal extracellular versus cellular organic matter 33:82 matter 77:82 A comparison of the character of algal extracellular versus cellular organic matter produced by cyanobacterium, diatom and green alga. 24388829 3 5 theme specific 712:719 arg1 absorbance 724:733 specific UV absorbance 712:733 specific UV absorbance (SUVA) 712:740 Extracellular organic matter (EOM) released at exponential and stationary growth phases and cellular organic matter (COM) were characterised in terms of specific UV absorbance (SUVA), peptide/protein and non-peptide content, hydrophobicity and molecular weight (MW). 24388829 3 5 theme specific 712:719 arg1 SUVA 736:739 SUVA 736:739 SUVA 736:739 Extracellular organic matter (EOM) released at exponential and stationary growth phases and cellular organic matter (COM) were characterised in terms of specific UV absorbance (SUVA), peptide/protein and non-peptide content, hydrophobicity and molecular weight (MW). 24388829 2 6 dep counting 476:483 arg1 measurements 545:556 concentration measurements 531:556 concentration measurements 531:556 Algal growth was monitored by cell counting, optical density and dissolved organic carbon concentration measurements. 24388829 2 7 theme dissolved 506:514 arg1 carbon 524:529 dissolved organic carbon 506:529 dissolved organic carbon 506:529 Algal growth was monitored by cell counting, optical density and dissolved organic carbon concentration measurements. 24388829 3 8 theme UV 721:722 arg1 absorbance 724:733 specific UV absorbance 712:733 specific UV absorbance (SUVA) 712:740 Extracellular organic matter (EOM) released at exponential and stationary growth phases and cellular organic matter (COM) were characterised in terms of specific UV absorbance (SUVA), peptide/protein and non-peptide content, hydrophobicity and molecular weight (MW). 24388829 3 8 theme UV 721:722 arg1 SUVA 736:739 SUVA 736:739 SUVA 736:739 Extracellular organic matter (EOM) released at exponential and stationary growth phases and cellular organic matter (COM) were characterised in terms of specific UV absorbance (SUVA), peptide/protein and non-peptide content, hydrophobicity and molecular weight (MW). 24388829 9 9 theme water 1609:1613 arg1 treatment 1586:1594 the treatment 1582:1594 the treatment of AOM laden water 1582:1613 The results imply that the knowledge of AOM composition and characteristics predetermine which processes would be effective in the treatment of AOM laden water. 24388829 8 10 theme high-MW 1398:1404 arg1 ones 1406:1409 high-MW ones 1398:1409 high-MW ones (22%) 1398:1415 The highest amount of peptides/proteins with a significant portion of high-MW ones (22%) was observed in COM of M. aeruginosa. 24388829 8 10 theme high-MW 1398:1404 arg1 % 1414:1414 22% 1412:1414 22% 1412:1414 The highest amount of peptides/proteins with a significant portion of high-MW ones (22%) was observed in COM of M. aeruginosa. 24388829 6 11 theme low-MW 1146:1151 arg1 compounds 1162:1170 low-MW (<1 kDa) compounds 1146:1170 low-MW (<1 kDa) compounds 1146:1170 MW fractionation showed that both EOM and COM of all three species contain large portions of low-MW (<1 kDa) compounds and high-MW (>100 kDa) polysaccharides. 24388829 8 12 theme ones 1406:1409 arg1 portion 1387:1393 a significant portion 1373:1393 a significant portion of high-MW ones (22%) 1373:1415 The highest amount of peptides/proteins with a significant portion of high-MW ones (22%) was observed in COM of M. aeruginosa. 24388829 1 13 theme phytoplanktonic 356:370 arg1 populations 372:382 phytoplanktonic populations 356:382 phytoplanktonic populations in reservoirs supplying drinking water treatment plants 356:438 This study investigated characteristics of algal organic matter (AOM) derived from three species (cyanobacterium Microcystis aeruginosa, diatom Fragilaria crotonensis and green alga Chlamydomonas geitleri) which dominate phytoplanktonic populations in reservoirs supplying drinking water treatment plants. 24388829 9 14 from treatment 1586:1594 arg1 effective 1569:1577 effective 1569:1577 effective 1569:1577 The results imply that the knowledge of AOM composition and characteristics predetermine which processes would be effective in the treatment of AOM laden water. 24388829 6 15 contain contain 1120:1126 arg2 portions 1134:1141 large portions 1128:1141 large portions of low-MW (<1 kDa) compounds and high-MW (>100 kDa) polysaccharides 1128:1209 MW fractionation showed that both EOM and COM of all three species contain large portions of low-MW (<1 kDa) compounds and high-MW (>100 kDa) polysaccharides. 24388829 6 15 contain contain 1120:1126 arg1 COM 1095:1097 COM 1095:1097 COM 1095:1097 MW fractionation showed that both EOM and COM of all three species contain large portions of low-MW (<1 kDa) compounds and high-MW (>100 kDa) polysaccharides. 24388829 6 15 contain contain 1120:1126 arg1 EOM 1087:1089 EOM 1087:1089 EOM 1087:1089 MW fractionation showed that both EOM and COM of all three species contain large portions of low-MW (<1 kDa) compounds and high-MW (>100 kDa) polysaccharides. 24388829 3 16 theme peptide/protein 743:757 arg1 terms 703:707 terms 703:707 terms of specific UV absorbance (SUVA), peptide/protein and non-peptide content, hydrophobicity and molecular weight (MW) 703:823 Extracellular organic matter (EOM) released at exponential and stationary growth phases and cellular organic matter (COM) were characterised in terms of specific UV absorbance (SUVA), peptide/protein and non-peptide content, hydrophobicity and molecular weight (MW). 24388829 3 17 theme organic 573:579 arg1 EOM 589:591 EOM 589:591 EOM 589:591 Extracellular organic matter (EOM) released at exponential and stationary growth phases and cellular organic matter (COM) were characterised in terms of specific UV absorbance (SUVA), peptide/protein and non-peptide content, hydrophobicity and molecular weight (MW). 24388829 3 17 theme organic 573:579 arg1 matter 581:586 Extracellular organic matter 559:586 Extracellular organic matter (EOM) released at exponential and stationary growth phases 559:645 Extracellular organic matter (EOM) released at exponential and stationary growth phases and cellular organic matter (COM) were characterised in terms of specific UV absorbance (SUVA), peptide/protein and non-peptide content, hydrophobicity and molecular weight (MW). 24388829 6 18 theme MW 1053:1054 arg1 fractionation 1056:1068 MW fractionation 1053:1068 MW fractionation 1053:1068 MW fractionation showed that both EOM and COM of all three species contain large portions of low-MW (<1 kDa) compounds and high-MW (>100 kDa) polysaccharides. 24388829 2 19 theme concentration 531:543 arg1 measurements 545:556 concentration measurements 531:556 concentration measurements 531:556 Algal growth was monitored by cell counting, optical density and dissolved organic carbon concentration measurements. 24388829 5 20 dep richer 915:920 arg1 fraction 992:999 hydrophilic fraction 980:999 hydrophilic fraction 980:999 COM was richer in peptides/proteins, more hydrophilic (with about 89% of hydrophilic fraction for all three species) and had lower SUVA than EOM. 24388829 5 20 dep richer 915:920 arg1 % 975:975 about 89% 967:975 about 89% of hydrophilic fraction for all three species 967:1021 COM was richer in peptides/proteins, more hydrophilic (with about 89% of hydrophilic fraction for all three species) and had lower SUVA than EOM. 24388829 2 21 theme cell 471:474 arg1 counting 476:483 cell counting 471:483 cell counting 471:483 Algal growth was monitored by cell counting, optical density and dissolved organic carbon concentration measurements. 24388829 6 22 theme polysaccharides 1195:1209 arg1 portions 1134:1141 large portions 1128:1141 large portions of low-MW (<1 kDa) compounds and high-MW (>100 kDa) polysaccharides 1128:1209 MW fractionation showed that both EOM and COM of all three species contain large portions of low-MW (<1 kDa) compounds and high-MW (>100 kDa) polysaccharides. 24388829 9 23 theme composition 1499:1509 arg1 characteristics 1515:1529 characteristics 1515:1529 characteristics 1515:1529 The results imply that the knowledge of AOM composition and characteristics predetermine which processes would be effective in the treatment of AOM laden water. 24388829 9 23 theme composition 1499:1509 arg1 knowledge 1482:1490 the knowledge 1478:1490 the knowledge of AOM composition 1478:1509 The results imply that the knowledge of AOM composition and characteristics predetermine which processes would be effective in the treatment of AOM laden water. 24388829 1 24 theme algal 178:182 arg1 AOM 200:202 AOM 200:202 AOM 200:202 This study investigated characteristics of algal organic matter (AOM) derived from three species (cyanobacterium Microcystis aeruginosa, diatom Fragilaria crotonensis and green alga Chlamydomonas geitleri) which dominate phytoplanktonic populations in reservoirs supplying drinking water treatment plants. 24388829 1 24 theme algal 178:182 arg1 matter 192:197 algal organic matter 178:197 algal organic matter (AOM) derived from three species (cyanobacterium Microcystis aeruginosa, diatom Fragilaria crotonensis and green alga Chlamydomonas geitleri) which dominate phytoplanktonic populations in reservoirs supplying drinking water treatment plants 178:438 This study investigated characteristics of algal organic matter (AOM) derived from three species (cyanobacterium Microcystis aeruginosa, diatom Fragilaria crotonensis and green alga Chlamydomonas geitleri) which dominate phytoplanktonic populations in reservoirs supplying drinking water treatment plants. 24388829 6 25 theme <1 kDa 1154:1159 arg1 compounds 1162:1170 low-MW (<1 kDa) compounds 1146:1170 low-MW (<1 kDa) compounds 1146:1170 MW fractionation showed that both EOM and COM of all three species contain large portions of low-MW (<1 kDa) compounds and high-MW (>100 kDa) polysaccharides. 24388829 3 26 theme exponential 606:616 arg1 phases 640:645 exponential and stationary growth phases 606:645 exponential and stationary growth phases 606:645 Extracellular organic matter (EOM) released at exponential and stationary growth phases and cellular organic matter (COM) were characterised in terms of specific UV absorbance (SUVA), peptide/protein and non-peptide content, hydrophobicity and molecular weight (MW). 24388829 1 27 theme drinking 408:415 arg1 plants 433:438 drinking water treatment plants 408:438 drinking water treatment plants 408:438 This study investigated characteristics of algal organic matter (AOM) derived from three species (cyanobacterium Microcystis aeruginosa, diatom Fragilaria crotonensis and green alga Chlamydomonas geitleri) which dominate phytoplanktonic populations in reservoirs supplying drinking water treatment plants. 24388829 1 28 theme diatom 272:277 arg1 crotonensis 290:300 diatom Fragilaria crotonensis 272:300 diatom Fragilaria crotonensis 272:300 This study investigated characteristics of algal organic matter (AOM) derived from three species (cyanobacterium Microcystis aeruginosa, diatom Fragilaria crotonensis and green alga Chlamydomonas geitleri) which dominate phytoplanktonic populations in reservoirs supplying drinking water treatment plants. 24388829 1 28 theme diatom 272:277 arg1 aeruginosa 260:269 cyanobacterium Microcystis aeruginosa 233:269 cyanobacterium Microcystis aeruginosa 233:269 This study investigated characteristics of algal organic matter (AOM) derived from three species (cyanobacterium Microcystis aeruginosa, diatom Fragilaria crotonensis and green alga Chlamydomonas geitleri) which dominate phytoplanktonic populations in reservoirs supplying drinking water treatment plants. 24388829 8 29 theme significant 1375:1385 arg1 portion 1387:1393 a significant portion 1373:1393 a significant portion of high-MW ones (22%) 1373:1415 The highest amount of peptides/proteins with a significant portion of high-MW ones (22%) was observed in COM of M. aeruginosa. 24388829 5 30 theme hydrophilic 949:959 arg1 peptides/proteins 925:941 peptides/proteins 925:941 peptides/proteins 925:941 COM was richer in peptides/proteins, more hydrophilic (with about 89% of hydrophilic fraction for all three species) and had lower SUVA than EOM. 24388829 6 31 theme >100 kDa 1185:1192 arg1 polysaccharides 1195:1209 high-MW (>100 kDa) polysaccharides 1176:1209 high-MW (>100 kDa) polysaccharides 1176:1209 MW fractionation showed that both EOM and COM of all three species contain large portions of low-MW (<1 kDa) compounds and high-MW (>100 kDa) polysaccharides. 24388829 1 32 theme matter 192:197 arg1 characteristics 159:173 characteristics 159:173 characteristics of algal organic matter (AOM) derived from three species (cyanobacterium Microcystis aeruginosa, diatom Fragilaria crotonensis and green alga Chlamydomonas geitleri) which dominate phytoplanktonic populations in reservoirs supplying drinking water treatment plants 159:438 This study investigated characteristics of algal organic matter (AOM) derived from three species (cyanobacterium Microcystis aeruginosa, diatom Fragilaria crotonensis and green alga Chlamydomonas geitleri) which dominate phytoplanktonic populations in reservoirs supplying drinking water treatment plants. 24388829 1 33 from populations 372:382 arg1 reservoirs 387:396 reservoirs 387:396 reservoirs supplying drinking water treatment plants 387:438 This study investigated characteristics of algal organic matter (AOM) derived from three species (cyanobacterium Microcystis aeruginosa, diatom Fragilaria crotonensis and green alga Chlamydomonas geitleri) which dominate phytoplanktonic populations in reservoirs supplying drinking water treatment plants. 24388829 1 34 theme Fragilaria 279:288 arg1 crotonensis 290:300 diatom Fragilaria crotonensis 272:300 diatom Fragilaria crotonensis 272:300 This study investigated characteristics of algal organic matter (AOM) derived from three species (cyanobacterium Microcystis aeruginosa, diatom Fragilaria crotonensis and green alga Chlamydomonas geitleri) which dominate phytoplanktonic populations in reservoirs supplying drinking water treatment plants. 24388829 1 34 theme Fragilaria 279:288 arg1 aeruginosa 260:269 cyanobacterium Microcystis aeruginosa 233:269 cyanobacterium Microcystis aeruginosa 233:269 This study investigated characteristics of algal organic matter (AOM) derived from three species (cyanobacterium Microcystis aeruginosa, diatom Fragilaria crotonensis and green alga Chlamydomonas geitleri) which dominate phytoplanktonic populations in reservoirs supplying drinking water treatment plants. 24388829 9 35 theme AOM 1495:1497 arg1 composition 1499:1509 AOM composition 1495:1509 AOM composition 1495:1509 The results imply that the knowledge of AOM composition and characteristics predetermine which processes would be effective in the treatment of AOM laden water. 24388829 2 36 theme optical 486:492 arg1 density 494:500 optical density 486:500 optical density 486:500 Algal growth was monitored by cell counting, optical density and dissolved organic carbon concentration measurements. 24388829 5 37 contain had 1028:1030 arg1 COM 907:909 COM 907:909 COM 907:909 COM was richer in peptides/proteins, more hydrophilic (with about 89% of hydrophilic fraction for all three species) and had lower SUVA than EOM. 24388829 5 37 contain had 1028:1030 arg2 SUVA 1038:1041 lower SUVA 1032:1041 lower SUVA 1032:1041 COM was richer in peptides/proteins, more hydrophilic (with about 89% of hydrophilic fraction for all three species) and had lower SUVA than EOM. 24388829 2 38 theme Algal 441:445 arg1 growth 447:452 Algal growth 441:452 Algal growth 441:452 Algal growth was monitored by cell counting, optical density and dissolved organic carbon concentration measurements. 24388829 3 39 theme non-peptide 763:773 arg1 content 775:781 non-peptide content 763:781 non-peptide content 763:781 Extracellular organic matter (EOM) released at exponential and stationary growth phases and cellular organic matter (COM) were characterised in terms of specific UV absorbance (SUVA), peptide/protein and non-peptide content, hydrophobicity and molecular weight (MW). 24388829 1 40 dep species 224:230 arg1 crotonensis 290:300 diatom Fragilaria crotonensis 272:300 diatom Fragilaria crotonensis 272:300 This study investigated characteristics of algal organic matter (AOM) derived from three species (cyanobacterium Microcystis aeruginosa, diatom Fragilaria crotonensis and green alga Chlamydomonas geitleri) which dominate phytoplanktonic populations in reservoirs supplying drinking water treatment plants. 24388829 1 40 dep species 224:230 arg1 alga 312:315 green alga 306:315 green alga 306:315 This study investigated characteristics of algal organic matter (AOM) derived from three species (cyanobacterium Microcystis aeruginosa, diatom Fragilaria crotonensis and green alga Chlamydomonas geitleri) which dominate phytoplanktonic populations in reservoirs supplying drinking water treatment plants. 24388829 1 40 dep species 224:230 arg1 aeruginosa 260:269 cyanobacterium Microcystis aeruginosa 233:269 cyanobacterium Microcystis aeruginosa 233:269 This study investigated characteristics of algal organic matter (AOM) derived from three species (cyanobacterium Microcystis aeruginosa, diatom Fragilaria crotonensis and green alga Chlamydomonas geitleri) which dominate phytoplanktonic populations in reservoirs supplying drinking water treatment plants. 24388829 3 41 theme growth 633:638 arg1 phases 640:645 exponential and stationary growth phases 606:645 exponential and stationary growth phases 606:645 Extracellular organic matter (EOM) released at exponential and stationary growth phases and cellular organic matter (COM) were characterised in terms of specific UV absorbance (SUVA), peptide/protein and non-peptide content, hydrophobicity and molecular weight (MW). 24388829 1 42 theme organic 184:190 arg1 AOM 200:202 AOM 200:202 AOM 200:202 This study investigated characteristics of algal organic matter (AOM) derived from three species (cyanobacterium Microcystis aeruginosa, diatom Fragilaria crotonensis and green alga Chlamydomonas geitleri) which dominate phytoplanktonic populations in reservoirs supplying drinking water treatment plants. 24388829 1 42 theme organic 184:190 arg1 matter 192:197 algal organic matter 178:197 algal organic matter (AOM) derived from three species (cyanobacterium Microcystis aeruginosa, diatom Fragilaria crotonensis and green alga Chlamydomonas geitleri) which dominate phytoplanktonic populations in reservoirs supplying drinking water treatment plants 178:438 This study investigated characteristics of algal organic matter (AOM) derived from three species (cyanobacterium Microcystis aeruginosa, diatom Fragilaria crotonensis and green alga Chlamydomonas geitleri) which dominate phytoplanktonic populations in reservoirs supplying drinking water treatment plants. 24388829 0 43 theme character 20:28 arg1 comparison 2:11 A comparison 0:11 A comparison of the character of algal extracellular versus cellular organic matter 0:82 A comparison of the character of algal extracellular versus cellular organic matter produced by cyanobacterium, diatom and green alga. 24388829 3 44 theme molecular 803:811 arg1 MW 821:822 MW 821:822 MW 821:822 Extracellular organic matter (EOM) released at exponential and stationary growth phases and cellular organic matter (COM) were characterised in terms of specific UV absorbance (SUVA), peptide/protein and non-peptide content, hydrophobicity and molecular weight (MW). 24388829 3 44 theme molecular 803:811 arg1 weight 813:818 molecular weight 803:818 molecular weight (MW) 803:823 Extracellular organic matter (EOM) released at exponential and stationary growth phases and cellular organic matter (COM) were characterised in terms of specific UV absorbance (SUVA), peptide/protein and non-peptide content, hydrophobicity and molecular weight (MW). 24388829 0 45 theme green 123:127 arg1 alga 129:132 green alga 123:132 green alga 123:132 A comparison of the character of algal extracellular versus cellular organic matter produced by cyanobacterium, diatom and green alga. 24388829 1 46 theme water 417:421 arg1 plants 433:438 drinking water treatment plants 408:438 drinking water treatment plants 408:438 This study investigated characteristics of algal organic matter (AOM) derived from three species (cyanobacterium Microcystis aeruginosa, diatom Fragilaria crotonensis and green alga Chlamydomonas geitleri) which dominate phytoplanktonic populations in reservoirs supplying drinking water treatment plants. 24388829 1 47 attach derived 205:211 arg2 AOM 200:202 AOM 200:202 AOM 200:202 This study investigated characteristics of algal organic matter (AOM) derived from three species (cyanobacterium Microcystis aeruginosa, diatom Fragilaria crotonensis and green alga Chlamydomonas geitleri) which dominate phytoplanktonic populations in reservoirs supplying drinking water treatment plants. 24388829 1 47 attach derived 205:211 arg1 species 224:230 three species 218:230 three species (cyanobacterium Microcystis aeruginosa, diatom Fragilaria crotonensis and green alga Chlamydomonas geitleri) which dominate phytoplanktonic populations in reservoirs supplying drinking water treatment plants 218:438 This study investigated characteristics of algal organic matter (AOM) derived from three species (cyanobacterium Microcystis aeruginosa, diatom Fragilaria crotonensis and green alga Chlamydomonas geitleri) which dominate phytoplanktonic populations in reservoirs supplying drinking water treatment plants. 24388829 1 47 attach derived 205:211 arg2 matter 192:197 algal organic matter 178:197 algal organic matter (AOM) derived from three species (cyanobacterium Microcystis aeruginosa, diatom Fragilaria crotonensis and green alga Chlamydomonas geitleri) which dominate phytoplanktonic populations in reservoirs supplying drinking water treatment plants 178:438 This study investigated characteristics of algal organic matter (AOM) derived from three species (cyanobacterium Microcystis aeruginosa, diatom Fragilaria crotonensis and green alga Chlamydomonas geitleri) which dominate phytoplanktonic populations in reservoirs supplying drinking water treatment plants. 24388829 7 48 theme non-peptide 1270:1280 arg1 fraction 1282:1289 non-peptide fraction 1270:1289 non-peptide fraction 1270:1289 Peptides/proteins exhibited narrower MW distribution than non-peptide fraction and it widened as the cultures grew. 24388829 0 49 theme extracellular 39:51 arg1 character 20:28 the character 16:28 the character of algal extracellular versus cellular organic matter 16:82 A comparison of the character of algal extracellular versus cellular organic matter produced by cyanobacterium, diatom and green alga. 24388829 1 50 theme green 306:310 arg1 alga 312:315 green alga 306:315 green alga 306:315 This study investigated characteristics of algal organic matter (AOM) derived from three species (cyanobacterium Microcystis aeruginosa, diatom Fragilaria crotonensis and green alga Chlamydomonas geitleri) which dominate phytoplanktonic populations in reservoirs supplying drinking water treatment plants. 24388829 1 50 theme green 306:310 arg1 aeruginosa 260:269 cyanobacterium Microcystis aeruginosa 233:269 cyanobacterium Microcystis aeruginosa 233:269 This study investigated characteristics of algal organic matter (AOM) derived from three species (cyanobacterium Microcystis aeruginosa, diatom Fragilaria crotonensis and green alga Chlamydomonas geitleri) which dominate phytoplanktonic populations in reservoirs supplying drinking water treatment plants. 24388829 1 51 theme treatment 423:431 arg1 plants 433:438 drinking water treatment plants 408:438 drinking water treatment plants 408:438 This study investigated characteristics of algal organic matter (AOM) derived from three species (cyanobacterium Microcystis aeruginosa, diatom Fragilaria crotonensis and green alga Chlamydomonas geitleri) which dominate phytoplanktonic populations in reservoirs supplying drinking water treatment plants. 24388829 6 52 theme high-MW 1176:1182 arg1 polysaccharides 1195:1209 high-MW (>100 kDa) polysaccharides 1176:1209 high-MW (>100 kDa) polysaccharides 1176:1209 MW fractionation showed that both EOM and COM of all three species contain large portions of low-MW (<1 kDa) compounds and high-MW (>100 kDa) polysaccharides. 24388829 8 53 theme highest 1332:1338 arg1 amount 1340:1345 The highest amount 1328:1345 The highest amount of peptides/proteins with a significant portion of high-MW ones (22%) 1328:1415 The highest amount of peptides/proteins with a significant portion of high-MW ones (22%) was observed in COM of M. aeruginosa. 24388829 8 53 theme highest 1332:1338 arg1 peptides/proteins 1350:1366 peptides/proteins 1350:1366 peptides/proteins with a significant portion of high-MW ones (22%) 1350:1415 The highest amount of peptides/proteins with a significant portion of high-MW ones (22%) was observed in COM of M. aeruginosa. 24388829 7 54 theme MW 1249:1250 arg1 distribution 1252:1263 narrower MW distribution 1240:1263 narrower MW distribution 1240:1263 Peptides/proteins exhibited narrower MW distribution than non-peptide fraction and it widened as the cultures grew. 24388829 3 55 theme hydrophobicity 784:797 arg1 terms 703:707 terms 703:707 terms of specific UV absorbance (SUVA), peptide/protein and non-peptide content, hydrophobicity and molecular weight (MW) 703:823 Extracellular organic matter (EOM) released at exponential and stationary growth phases and cellular organic matter (COM) were characterised in terms of specific UV absorbance (SUVA), peptide/protein and non-peptide content, hydrophobicity and molecular weight (MW). 24388829 4 56 theme low 897:899 arg1 SUVA 901:904 low SUVA 897:904 low SUVA 897:904 It was found that both EOM and COM were predominantly hydrophilic with low SUVA. 24388829 3 57 theme stationary 622:631 arg1 phases 640:645 exponential and stationary growth phases 606:645 exponential and stationary growth phases 606:645 Extracellular organic matter (EOM) released at exponential and stationary growth phases and cellular organic matter (COM) were characterised in terms of specific UV absorbance (SUVA), peptide/protein and non-peptide content, hydrophobicity and molecular weight (MW). 24388829 9 58 theme laden 1603:1607 arg1 water 1609:1613 AOM laden water 1599:1613 AOM laden water 1599:1613 The results imply that the knowledge of AOM composition and characteristics predetermine which processes would be effective in the treatment of AOM laden water. 24388829 1 59 theme Chlamydomonas 317:329 arg1 geitleri 331:338 Chlamydomonas geitleri 317:338 Chlamydomonas geitleri 317:338 This study investigated characteristics of algal organic matter (AOM) derived from three species (cyanobacterium Microcystis aeruginosa, diatom Fragilaria crotonensis and green alga Chlamydomonas geitleri) which dominate phytoplanktonic populations in reservoirs supplying drinking water treatment plants. 24388829 6 60 theme compounds 1162:1170 arg1 portions 1134:1141 large portions 1128:1141 large portions of low-MW (<1 kDa) compounds and high-MW (>100 kDa) polysaccharides 1128:1209 MW fractionation showed that both EOM and COM of all three species contain large portions of low-MW (<1 kDa) compounds and high-MW (>100 kDa) polysaccharides. 24388829 3 61 theme organic 660:666 arg1 COM 676:678 COM 676:678 COM 676:678 Extracellular organic matter (EOM) released at exponential and stationary growth phases and cellular organic matter (COM) were characterised in terms of specific UV absorbance (SUVA), peptide/protein and non-peptide content, hydrophobicity and molecular weight (MW). 24388829 3 61 theme organic 660:666 arg1 matter 668:673 cellular organic matter 651:673 cellular organic matter (COM) 651:679 Extracellular organic matter (EOM) released at exponential and stationary growth phases and cellular organic matter (COM) were characterised in terms of specific UV absorbance (SUVA), peptide/protein and non-peptide content, hydrophobicity and molecular weight (MW). 24388829 9 62 from effective 1569:1577 arg1 treatment 1586:1594 the treatment 1582:1594 the treatment of AOM laden water 1582:1613 The results imply that the knowledge of AOM composition and characteristics predetermine which processes would be effective in the treatment of AOM laden water. 24388829 4 63 with hydrophilic 880:890 arg1 SUVA 901:904 low SUVA 897:904 low SUVA 897:904 It was found that both EOM and COM were predominantly hydrophilic with low SUVA. 24388829 6 64 theme large 1128:1132 arg1 portions 1134:1141 large portions 1128:1141 large portions of low-MW (<1 kDa) compounds and high-MW (>100 kDa) polysaccharides 1128:1209 MW fractionation showed that both EOM and COM of all three species contain large portions of low-MW (<1 kDa) compounds and high-MW (>100 kDa) polysaccharides. 24388829 5 65 theme lower 1032:1036 arg1 SUVA 1038:1041 lower SUVA 1032:1041 lower SUVA 1032:1041 COM was richer in peptides/proteins, more hydrophilic (with about 89% of hydrophilic fraction for all three species) and had lower SUVA than EOM. 24388829 5 66 theme hydrophilic 980:990 arg1 fraction 992:999 hydrophilic fraction 980:999 hydrophilic fraction 980:999 COM was richer in peptides/proteins, more hydrophilic (with about 89% of hydrophilic fraction for all three species) and had lower SUVA than EOM. 24388829 7 67 theme narrower 1240:1247 arg1 distribution 1252:1263 narrower MW distribution 1240:1263 narrower MW distribution 1240:1263 Peptides/proteins exhibited narrower MW distribution than non-peptide fraction and it widened as the cultures grew. 24388829 0 68 theme cellular 60:67 arg1 matter 77:82 algal extracellular versus cellular organic matter 33:82 matter 77:82 A comparison of the character of algal extracellular versus cellular organic matter produced by cyanobacterium, diatom and green alga. 24388829 8 69 theme peptides/proteins 1350:1366 arg1 amount 1340:1345 The highest amount 1328:1345 The highest amount of peptides/proteins with a significant portion of high-MW ones (22%) 1328:1415 The highest amount of peptides/proteins with a significant portion of high-MW ones (22%) was observed in COM of M. aeruginosa. 24388829 8 69 theme peptides/proteins 1350:1366 arg1 peptides/proteins 1350:1366 peptides/proteins 1350:1366 peptides/proteins with a significant portion of high-MW ones (22%) 1350:1415 The highest amount of peptides/proteins with a significant portion of high-MW ones (22%) was observed in COM of M. aeruginosa. 24388829 5 70 theme fraction 992:999 arg1 fraction 992:999 hydrophilic fraction 980:999 hydrophilic fraction 980:999 COM was richer in peptides/proteins, more hydrophilic (with about 89% of hydrophilic fraction for all three species) and had lower SUVA than EOM. 24388829 5 70 theme fraction 992:999 arg1 % 975:975 about 89% 967:975 about 89% of hydrophilic fraction for all three species 967:1021 COM was richer in peptides/proteins, more hydrophilic (with about 89% of hydrophilic fraction for all three species) and had lower SUVA than EOM. 24388829 6 71 theme species 1112:1118 arg1 COM 1095:1097 COM 1095:1097 COM 1095:1097 MW fractionation showed that both EOM and COM of all three species contain large portions of low-MW (<1 kDa) compounds and high-MW (>100 kDa) polysaccharides. 24388829 6 71 theme species 1112:1118 arg1 EOM 1087:1089 EOM 1087:1089 EOM 1087:1089 MW fractionation showed that both EOM and COM of all three species contain large portions of low-MW (<1 kDa) compounds and high-MW (>100 kDa) polysaccharides. 24388829 2 72 theme organic 516:522 arg1 carbon 524:529 dissolved organic carbon 506:529 dissolved organic carbon 506:529 Algal growth was monitored by cell counting, optical density and dissolved organic carbon concentration measurements. 24388829 3 73 theme absorbance 724:733 arg1 terms 703:707 terms 703:707 terms of specific UV absorbance (SUVA), peptide/protein and non-peptide content, hydrophobicity and molecular weight (MW) 703:823 Extracellular organic matter (EOM) released at exponential and stationary growth phases and cellular organic matter (COM) were characterised in terms of specific UV absorbance (SUVA), peptide/protein and non-peptide content, hydrophobicity and molecular weight (MW). 24388829 3 74 theme cellular 651:658 arg1 COM 676:678 COM 676:678 COM 676:678 Extracellular organic matter (EOM) released at exponential and stationary growth phases and cellular organic matter (COM) were characterised in terms of specific UV absorbance (SUVA), peptide/protein and non-peptide content, hydrophobicity and molecular weight (MW). 24388829 3 74 theme cellular 651:658 arg1 matter 668:673 cellular organic matter 651:673 cellular organic matter (COM) 651:679 Extracellular organic matter (EOM) released at exponential and stationary growth phases and cellular organic matter (COM) were characterised in terms of specific UV absorbance (SUVA), peptide/protein and non-peptide content, hydrophobicity and molecular weight (MW). 24388829 3 75 theme Extracellular 559:571 arg1 EOM 589:591 EOM 589:591 EOM 589:591 Extracellular organic matter (EOM) released at exponential and stationary growth phases and cellular organic matter (COM) were characterised in terms of specific UV absorbance (SUVA), peptide/protein and non-peptide content, hydrophobicity and molecular weight (MW). 24388829 3 75 theme Extracellular 559:571 arg1 matter 581:586 Extracellular organic matter 559:586 Extracellular organic matter (EOM) released at exponential and stationary growth phases 559:645 Extracellular organic matter (EOM) released at exponential and stationary growth phases and cellular organic matter (COM) were characterised in terms of specific UV absorbance (SUVA), peptide/protein and non-peptide content, hydrophobicity and molecular weight (MW). 24388829 8 76 located observed 1421:1428 arg2 peptides/proteins 1350:1366 peptides/proteins 1350:1366 peptides/proteins with a significant portion of high-MW ones (22%) 1350:1415 The highest amount of peptides/proteins with a significant portion of high-MW ones (22%) was observed in COM of M. aeruginosa. 24388829 8 76 located observed 1421:1428 arg2 amount 1340:1345 The highest amount 1328:1345 The highest amount of peptides/proteins with a significant portion of high-MW ones (22%) 1328:1415 The highest amount of peptides/proteins with a significant portion of high-MW ones (22%) was observed in COM of M. aeruginosa. 24388829 8 76 located observed 1421:1428 arg1 COM 1433:1435 COM 1433:1435 COM 1433:1435 The highest amount of peptides/proteins with a significant portion of high-MW ones (22%) was observed in COM of M. aeruginosa. 24388829 3 77 theme weight 813:818 arg1 terms 703:707 terms 703:707 terms of specific UV absorbance (SUVA), peptide/protein and non-peptide content, hydrophobicity and molecular weight (MW) 703:823 Extracellular organic matter (EOM) released at exponential and stationary growth phases and cellular organic matter (COM) were characterised in terms of specific UV absorbance (SUVA), peptide/protein and non-peptide content, hydrophobicity and molecular weight (MW). 27158904 0 0 theme aryl 79:82 arg1 ligands 105:111 aryl hydrocarbon receptor ligands 79:111 aryl hydrocarbon receptor ligands 79:111 CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands. 27158904 6 1 with treatment 1046:1054 arg1 agonist 1068:1074 an AHR agonist 1061:1074 an AHR agonist 1061:1074 Intestinal inflammation is attenuated after inoculation of mice with three Lactobacillus strains capable of metabolizing tryptophan or by treatment with an AHR agonist. 27158904 2 2 theme susceptibility 346:359 arg1 microbiota 277:286 gut microbiota and caspase recruitment domain family member 9 273:333 microbiota 277:286 Here we reveal a relationship between gut microbiota and caspase recruitment domain family member 9 (CARD9), a susceptibility gene for inflammatory bowel disease (IBD) that functions in the immune response against microorganisms. 27158904 2 2 theme susceptibility 346:359 arg1 gene 361:364 a susceptibility gene 344:364 a susceptibility gene for inflammatory bowel disease (IBD) that functions in the immune response against microorganisms 344:462 Here we reveal a relationship between gut microbiota and caspase recruitment domain family member 9 (CARD9), a susceptibility gene for inflammatory bowel disease (IBD) that functions in the immune response against microorganisms. 27158904 1 3 theme gut 160:162 arg1 microbiota 164:173 the gut microbiota 156:173 the gut microbiota 156:173 Complex interactions between the host and the gut microbiota govern intestinal homeostasis but remain poorly understood. 27158904 6 4 theme Intestinal 908:917 arg1 inflammation 919:930 Intestinal inflammation 908:930 Intestinal inflammation 908:930 Intestinal inflammation is attenuated after inoculation of mice with three Lactobacillus strains capable of metabolizing tryptophan or by treatment with an AHR agonist. 27158904 0 5 theme receptor 96:103 arg1 ligands 105:111 aryl hydrocarbon receptor ligands 79:111 aryl hydrocarbon receptor ligands 79:111 CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands. 27158904 6 6 with inoculation 952:962 arg1 strains 997:1003 three Lactobacillus strains 977:1003 three Lactobacillus strains capable of metabolizing tryptophan 977:1038 Intestinal inflammation is attenuated after inoculation of mice with three Lactobacillus strains capable of metabolizing tryptophan or by treatment with an AHR agonist. 27158904 2 7 theme recruitment 300:310 arg1 member 326:331 gut microbiota and caspase recruitment domain family member 9 273:333 member 326:331 Here we reveal a relationship between gut microbiota and caspase recruitment domain family member 9 (CARD9), a susceptibility gene for inflammatory bowel disease (IBD) that functions in the immune response against microorganisms. 27158904 5 8 theme hydrocarbon 872:882 arg1 AHR 894:896 AHR 894:896 AHR 894:896 The microbiota from Card9(-/-) mice fails to metabolize tryptophan into metabolites that act as aryl hydrocarbon receptor (AHR) ligands. 27158904 5 8 theme hydrocarbon 872:882 arg1 receptor 884:891 aryl hydrocarbon receptor 867:891 aryl hydrocarbon receptor (AHR) ligands 867:905 The microbiota from Card9(-/-) mice fails to metabolize tryptophan into metabolites that act as aryl hydrocarbon receptor (AHR) ligands. 27158904 0 9 theme hydrocarbon 84:94 arg1 ligands 105:111 aryl hydrocarbon receptor ligands 79:111 aryl hydrocarbon receptor ligands 79:111 CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands. 27158904 5 10 from mice 802:805 arg1 microbiota 775:784 The microbiota 771:784 The microbiota from Card9(-/-) mice 771:805 The microbiota from Card9(-/-) mice fails to metabolize tryptophan into metabolites that act as aryl hydrocarbon receptor (AHR) ligands. 27158904 2 11 theme caspase 292:298 arg1 member 326:331 gut microbiota and caspase recruitment domain family member 9 273:333 member 326:331 Here we reveal a relationship between gut microbiota and caspase recruitment domain family member 9 (CARD9), a susceptibility gene for inflammatory bowel disease (IBD) that functions in the immune response against microorganisms. 27158904 6 12 theme AHR 1064:1066 arg1 agonist 1068:1074 an AHR agonist 1061:1074 an AHR agonist 1061:1074 Intestinal inflammation is attenuated after inoculation of mice with three Lactobacillus strains capable of metabolizing tryptophan or by treatment with an AHR agonist. 27158904 4 13 theme wild-type 696:704 arg1 recipients 717:726 wild-type, germ-free recipients 696:726 recipients 717:726 The microbiota is altered in Card9(-/-) mice, and transfer of the microbiota from Card9(-/-) to wild-type, germ-free recipients increases their susceptibility to colitis. 27158904 1 14 theme intestinal 182:191 arg1 homeostasis 193:203 intestinal homeostasis 182:203 intestinal homeostasis 182:203 Complex interactions between the host and the gut microbiota govern intestinal homeostasis but remain poorly understood. 27158904 5 15 theme Card9 791:795 arg1 mice 802:805 Card9(-/-) mice 791:805 Card9(-/-) mice 791:805 The microbiota from Card9(-/-) mice fails to metabolize tryptophan into metabolites that act as aryl hydrocarbon receptor (AHR) ligands. 27158904 7 16 theme Reduced 1077:1083 arg1 production 1085:1094 Reduced production 1077:1094 Reduced production of AHR ligands 1077:1109 Reduced production of AHR ligands is also observed in the microbiota from individuals with IBD, particularly in those with CARD9 risk alleles associated with IBD. 27158904 6 17 theme capable 1005:1011 arg1 strains 997:1003 three Lactobacillus strains 977:1003 three Lactobacillus strains capable of metabolizing tryptophan 977:1038 Intestinal inflammation is attenuated after inoculation of mice with three Lactobacillus strains capable of metabolizing tryptophan or by treatment with an AHR agonist. 27158904 7 18 theme ligands 1103:1109 arg1 production 1085:1094 Reduced production 1077:1094 Reduced production of AHR ligands 1077:1109 Reduced production of AHR ligands is also observed in the microbiota from individuals with IBD, particularly in those with CARD9 risk alleles associated with IBD. 27158904 4 19 from Card9 682:686 arg1 transfer 650:657 transfer 650:657 transfer of the microbiota from Card9(-/-) to wild-type, germ-free recipients 650:726 The microbiota is altered in Card9(-/-) mice, and transfer of the microbiota from Card9(-/-) to wild-type, germ-free recipients increases their susceptibility to colitis. 27158904 4 19 from Card9 682:686 arg1 microbiota 666:675 the microbiota 662:675 the microbiota from Card9(-/-) 662:691 The microbiota is altered in Card9(-/-) mice, and transfer of the microbiota from Card9(-/-) to wild-type, germ-free recipients increases their susceptibility to colitis. 27158904 3 20 theme Card9 551:555 arg1 mice 562:565 Card9(-/-) mice 551:565 Card9(-/-) mice 551:565 CARD9 promotes recovery from colitis by promoting interleukin (IL)-22 production, and Card9(-/-) mice are more susceptible to colitis. 27158904 2 21 theme bowel 383:387 arg1 disease 389:395 inflammatory bowel disease 370:395 inflammatory bowel disease (IBD) 370:401 Here we reveal a relationship between gut microbiota and caspase recruitment domain family member 9 (CARD9), a susceptibility gene for inflammatory bowel disease (IBD) that functions in the immune response against microorganisms. 27158904 2 21 theme bowel 383:387 arg1 IBD 398:400 IBD 398:400 IBD 398:400 Here we reveal a relationship between gut microbiota and caspase recruitment domain family member 9 (CARD9), a susceptibility gene for inflammatory bowel disease (IBD) that functions in the immune response against microorganisms. 27158904 2 22 theme immune 425:430 arg1 response 432:439 the immune response 421:439 the immune response against microorganisms 421:462 Here we reveal a relationship between gut microbiota and caspase recruitment domain family member 9 (CARD9), a susceptibility gene for inflammatory bowel disease (IBD) that functions in the immune response against microorganisms. 27158904 4 23 theme microbiota 666:675 arg1 transfer 650:657 transfer 650:657 transfer of the microbiota from Card9(-/-) to wild-type, germ-free recipients 650:726 The microbiota is altered in Card9(-/-) mice, and transfer of the microbiota from Card9(-/-) to wild-type, germ-free recipients increases their susceptibility to colitis. 27158904 2 24 theme inflammatory 370:381 arg1 disease 389:395 inflammatory bowel disease 370:395 inflammatory bowel disease (IBD) 370:401 Here we reveal a relationship between gut microbiota and caspase recruitment domain family member 9 (CARD9), a susceptibility gene for inflammatory bowel disease (IBD) that functions in the immune response against microorganisms. 27158904 2 24 theme inflammatory 370:381 arg1 IBD 398:400 IBD 398:400 IBD 398:400 Here we reveal a relationship between gut microbiota and caspase recruitment domain family member 9 (CARD9), a susceptibility gene for inflammatory bowel disease (IBD) that functions in the immune response against microorganisms. 27158904 8 25 theme metabolites 1372:1382 arg1 production 1348:1357 the production 1344:1357 the production of microbial metabolites and intestinal inflammation 1344:1410 Our findings reveal that host genes affect the composition and function of the gut microbiota, altering the production of microbial metabolites and intestinal inflammation. 27158904 3 26 from colitis 494:500 arg1 recovery 480:487 recovery 480:487 recovery from colitis 480:500 CARD9 promotes recovery from colitis by promoting interleukin (IL)-22 production, and Card9(-/-) mice are more susceptible to colitis. 27158904 2 27 theme family 319:324 arg1 member 326:331 gut microbiota and caspase recruitment domain family member 9 273:333 member 326:331 Here we reveal a relationship between gut microbiota and caspase recruitment domain family member 9 (CARD9), a susceptibility gene for inflammatory bowel disease (IBD) that functions in the immune response against microorganisms. 27158904 7 28 theme AHR 1099:1101 arg1 ligands 1103:1109 AHR ligands 1099:1109 AHR ligands 1099:1109 Reduced production of AHR ligands is also observed in the microbiota from individuals with IBD, particularly in those with CARD9 risk alleles associated with IBD. 27158904 5 29 theme aryl 867:870 arg1 AHR 894:896 AHR 894:896 AHR 894:896 The microbiota from Card9(-/-) mice fails to metabolize tryptophan into metabolites that act as aryl hydrocarbon receptor (AHR) ligands. 27158904 5 29 theme aryl 867:870 arg1 receptor 884:891 aryl hydrocarbon receptor 867:891 aryl hydrocarbon receptor (AHR) ligands 867:905 The microbiota from Card9(-/-) mice fails to metabolize tryptophan into metabolites that act as aryl hydrocarbon receptor (AHR) ligands. 27158904 2 30 theme domain 312:317 arg1 member 326:331 gut microbiota and caspase recruitment domain family member 9 273:333 member 326:331 Here we reveal a relationship between gut microbiota and caspase recruitment domain family member 9 (CARD9), a susceptibility gene for inflammatory bowel disease (IBD) that functions in the immune response against microorganisms. 27158904 0 31 theme gut 34:36 arg1 metabolism 49:58 gut microbiota metabolism 34:58 gut microbiota metabolism of tryptophan 34:72 CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands. 27158904 4 32 theme Card9 629:633 arg1 mice 640:643 Card9(-/-) mice 629:643 Card9(-/-) mice 629:643 The microbiota is altered in Card9(-/-) mice, and transfer of the microbiota from Card9(-/-) to wild-type, germ-free recipients increases their susceptibility to colitis. 27158904 6 33 theme mice 967:970 arg1 inoculation 952:962 inoculation 952:962 inoculation of mice with three Lactobacillus strains capable of metabolizing tryptophan or by treatment with an AHR agonist 952:1074 Intestinal inflammation is attenuated after inoculation of mice with three Lactobacillus strains capable of metabolizing tryptophan or by treatment with an AHR agonist. 27158904 5 34 theme -/- 797:799 arg1 mice 802:805 Card9(-/-) mice 791:805 Card9(-/-) mice 791:805 The microbiota from Card9(-/-) mice fails to metabolize tryptophan into metabolites that act as aryl hydrocarbon receptor (AHR) ligands. 27158904 8 35 theme microbial 1362:1370 arg1 metabolites 1372:1382 microbial metabolites 1362:1382 microbial metabolites 1362:1382 Our findings reveal that host genes affect the composition and function of the gut microbiota, altering the production of microbial metabolites and intestinal inflammation. 27158904 8 36 theme host 1265:1268 arg1 genes 1270:1274 host genes 1265:1274 host genes 1265:1274 Our findings reveal that host genes affect the composition and function of the gut microbiota, altering the production of microbial metabolites and intestinal inflammation. 27158904 7 37 theme CARD9 1200:1204 arg1 alleles 1211:1217 CARD9 risk alleles 1200:1217 CARD9 risk alleles associated with IBD 1200:1237 Reduced production of AHR ligands is also observed in the microbiota from individuals with IBD, particularly in those with CARD9 risk alleles associated with IBD. 27158904 3 38 theme -/- 557:559 arg1 mice 562:565 Card9(-/-) mice 551:565 Card9(-/-) mice 551:565 CARD9 promotes recovery from colitis by promoting interleukin (IL)-22 production, and Card9(-/-) mice are more susceptible to colitis. 27158904 1 39 theme Complex 114:120 arg1 interactions 122:133 Complex interactions 114:133 Complex interactions between the host and the gut microbiota 114:173 Complex interactions between the host and the gut microbiota govern intestinal homeostasis but remain poorly understood. 27158904 0 40 theme microbiota 38:47 arg1 metabolism 49:58 gut microbiota metabolism 34:58 gut microbiota metabolism of tryptophan 34:72 CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands. 27158904 8 41 theme microbiota 1323:1332 arg1 composition 1287:1297 composition 1287:1297 composition 1287:1297 Our findings reveal that host genes affect the composition and function of the gut microbiota, altering the production of microbial metabolites and intestinal inflammation. 27158904 8 41 theme microbiota 1323:1332 arg1 function 1303:1310 function 1303:1310 function 1303:1310 Our findings reveal that host genes affect the composition and function of the gut microbiota, altering the production of microbial metabolites and intestinal inflammation. 27158904 6 42 theme Lactobacillus 983:995 arg1 strains 997:1003 three Lactobacillus strains 977:1003 three Lactobacillus strains capable of metabolizing tryptophan 977:1038 Intestinal inflammation is attenuated after inoculation of mice with three Lactobacillus strains capable of metabolizing tryptophan or by treatment with an AHR agonist. 27158904 8 43 theme inflammation 1399:1410 arg1 production 1348:1357 the production 1344:1357 the production of microbial metabolites and intestinal inflammation 1344:1410 Our findings reveal that host genes affect the composition and function of the gut microbiota, altering the production of microbial metabolites and intestinal inflammation. 27158904 8 44 theme gut 1319:1321 arg1 microbiota 1323:1332 the gut microbiota 1315:1332 the gut microbiota 1315:1332 Our findings reveal that host genes affect the composition and function of the gut microbiota, altering the production of microbial metabolites and intestinal inflammation. 27158904 7 45 located observed 1119:1126 arg2 production 1085:1094 Reduced production 1077:1094 Reduced production of AHR ligands 1077:1109 Reduced production of AHR ligands is also observed in the microbiota from individuals with IBD, particularly in those with CARD9 risk alleles associated with IBD. 27158904 7 45 located observed 1119:1126 arg1 microbiota 1135:1144 the microbiota 1131:1144 the microbiota from individuals with IBD 1131:1170 Reduced production of AHR ligands is also observed in the microbiota from individuals with IBD, particularly in those with CARD9 risk alleles associated with IBD. 27158904 7 45 located observed 1119:1126 arg1 those 1189:1193 those 1189:1193 those 1189:1193 Reduced production of AHR ligands is also observed in the microbiota from individuals with IBD, particularly in those with CARD9 risk alleles associated with IBD. 27158904 7 46 theme risk 1206:1209 arg1 alleles 1211:1217 CARD9 risk alleles 1200:1217 CARD9 risk alleles associated with IBD 1200:1237 Reduced production of AHR ligands is also observed in the microbiota from individuals with IBD, particularly in those with CARD9 risk alleles associated with IBD. 27158904 4 47 theme germ-free 707:715 arg1 recipients 717:726 wild-type, germ-free recipients 696:726 recipients 717:726 The microbiota is altered in Card9(-/-) mice, and transfer of the microbiota from Card9(-/-) to wild-type, germ-free recipients increases their susceptibility to colitis. 27158904 2 48 theme gut 273:275 arg1 microbiota 277:286 gut microbiota and caspase recruitment domain family member 9 273:333 microbiota 277:286 Here we reveal a relationship between gut microbiota and caspase recruitment domain family member 9 (CARD9), a susceptibility gene for inflammatory bowel disease (IBD) that functions in the immune response against microorganisms. 27158904 2 48 theme gut 273:275 arg1 gene 361:364 a susceptibility gene 344:364 a susceptibility gene for inflammatory bowel disease (IBD) that functions in the immune response against microorganisms 344:462 Here we reveal a relationship between gut microbiota and caspase recruitment domain family member 9 (CARD9), a susceptibility gene for inflammatory bowel disease (IBD) that functions in the immune response against microorganisms. 27158904 2 48 theme gut 273:275 arg1 CARD9 336:340 CARD9 336:340 CARD9 336:340 Here we reveal a relationship between gut microbiota and caspase recruitment domain family member 9 (CARD9), a susceptibility gene for inflammatory bowel disease (IBD) that functions in the immune response against microorganisms. 27158904 1 49 dep host 147:150 arg1 the 143:145 the 143:145 the 143:145 Complex interactions between the host and the gut microbiota govern intestinal homeostasis but remain poorly understood. 27158904 7 50 from individuals 1151:1161 arg1 microbiota 1135:1144 the microbiota 1131:1144 the microbiota from individuals with IBD 1131:1170 Reduced production of AHR ligands is also observed in the microbiota from individuals with IBD, particularly in those with CARD9 risk alleles associated with IBD. 27158904 5 51 theme receptor 884:891 arg1 ligands 899:905 aryl hydrocarbon receptor (AHR) ligands 867:905 aryl hydrocarbon receptor (AHR) ligands 867:905 The microbiota from Card9(-/-) mice fails to metabolize tryptophan into metabolites that act as aryl hydrocarbon receptor (AHR) ligands. 27158904 5 51 theme receptor 884:891 arg1 metabolites 843:853 metabolites 843:853 metabolites that act as aryl hydrocarbon receptor (AHR) ligands 843:905 The microbiota from Card9(-/-) mice fails to metabolize tryptophan into metabolites that act as aryl hydrocarbon receptor (AHR) ligands. 27158904 8 52 theme intestinal 1388:1397 arg1 inflammation 1399:1410 intestinal inflammation 1388:1410 intestinal inflammation 1388:1410 Our findings reveal that host genes affect the composition and function of the gut microbiota, altering the production of microbial metabolites and intestinal inflammation. 27158904 4 53 from transfer 650:657 arg1 Card9 682:686 Card9 682:686 Card9(-/-) 682:691 The microbiota is altered in Card9(-/-) mice, and transfer of the microbiota from Card9(-/-) to wild-type, germ-free recipients increases their susceptibility to colitis. 27158904 4 53 from transfer 650:657 arg1 -/- 688:690 -/- 688:690 -/- 688:690 The microbiota is altered in Card9(-/-) mice, and transfer of the microbiota from Card9(-/-) to wild-type, germ-free recipients increases their susceptibility to colitis. 27158904 0 54 theme tryptophan 63:72 arg1 metabolism 49:58 gut microbiota metabolism 34:58 gut microbiota metabolism of tryptophan 34:72 CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands. 27158904 7 55 with individuals 1151:1161 arg1 IBD 1168:1170 IBD 1168:1170 IBD 1168:1170 Reduced production of AHR ligands is also observed in the microbiota from individuals with IBD, particularly in those with CARD9 risk alleles associated with IBD. 27158904 3 56 theme interleukin 515:525 arg1 production 535:544 interleukin (IL)-22 production 515:544 interleukin (IL)-22 production 515:544 CARD9 promotes recovery from colitis by promoting interleukin (IL)-22 production, and Card9(-/-) mice are more susceptible to colitis. 27158904 4 57 theme -/- 635:637 arg1 mice 640:643 Card9(-/-) mice 629:643 Card9(-/-) mice 629:643 The microbiota is altered in Card9(-/-) mice, and transfer of the microbiota from Card9(-/-) to wild-type, germ-free recipients increases their susceptibility to colitis. 27158904 8 58 dep composition 1287:1297 arg1 the 1283:1285 the 1283:1285 the 1283:1285 Our findings reveal that host genes affect the composition and function of the gut microbiota, altering the production of microbial metabolites and intestinal inflammation. 28322582 1 0 theme epitopes 301:308 arg1 masking 257:263 the masking 253:263 the masking of conserved V3 crown (GPG) and V2i epitopes on the hypervariable loops of most exposed distal surface of HIV-1 Env 253:379 This study aimed to explore the contribution of high-mannose glycans in the masking of conserved V3 crown (GPG) and V2i epitopes on the hypervariable loops of most exposed distal surface of HIV-1 Env. 28322582 0 1 theme Envelope 171:178 arg1 V1/V2 129:133 V1/V2 129:133 V1/V2 129:133 Short Communication: Manα1-2Man-Binding Anti-HIV Lectins Enhance the Exposure of V2i and V3 Crown Neutralization Epitopes on the V1/V2 and V3 Hypervariable Loops of HIV-1 Envelope. 28322582 0 1 theme Envelope 171:178 arg1 Loops 156:160 V3 Hypervariable Loops 139:160 V3 Hypervariable Loops 139:160 Short Communication: Manα1-2Man-Binding Anti-HIV Lectins Enhance the Exposure of V2i and V3 Crown Neutralization Epitopes on the V1/V2 and V3 Hypervariable Loops of HIV-1 Envelope. 28322582 1 2 theme glycans 242:248 arg1 contribution 213:224 the contribution 209:224 the contribution of high-mannose glycans in the masking of conserved V3 crown (GPG) and V2i epitopes on the hypervariable loops of most exposed distal surface of HIV-1 Env 209:379 This study aimed to explore the contribution of high-mannose glycans in the masking of conserved V3 crown (GPG) and V2i epitopes on the hypervariable loops of most exposed distal surface of HIV-1 Env. 28322582 0 3 theme V2i 81:83 arg1 Exposure 69:76 the Exposure 65:76 the Exposure of V2i and V3 Crown Neutralization Epitopes 65:120 Short Communication: Manα1-2Man-Binding Anti-HIV Lectins Enhance the Exposure of V2i and V3 Crown Neutralization Epitopes on the V1/V2 and V3 Hypervariable Loops of HIV-1 Envelope. 28322582 0 4 theme HIV-1 165:169 arg1 Envelope 171:178 HIV-1 Envelope 165:178 HIV-1 Envelope 165:178 Short Communication: Manα1-2Man-Binding Anti-HIV Lectins Enhance the Exposure of V2i and V3 Crown Neutralization Epitopes on the V1/V2 and V3 Hypervariable Loops of HIV-1 Envelope. 28322582 2 5 theme antibodies 668:677 arg1 strength 656:663 the neutralization strength 637:663 the neutralization strength of antibodies against these epitopes 637:700 Using lectins specific to Manα1-2Man residue containing Man6-9GlcNAc2 glycans extensively decorating HIV-1 Env, we found that Manα1-2Man-binding lectins enhance the exposure of these partially and transiently exposed epitopes and consequentially increase the neutralization strength of antibodies against these epitopes. 28322582 2 6 theme epitopes 599:606 arg1 exposure 547:554 the exposure 543:554 the exposure of these partially and transiently exposed epitopes 543:606 Using lectins specific to Manα1-2Man residue containing Man6-9GlcNAc2 glycans extensively decorating HIV-1 Env, we found that Manα1-2Man-binding lectins enhance the exposure of these partially and transiently exposed epitopes and consequentially increase the neutralization strength of antibodies against these epitopes. 28322582 0 7 theme Crown 92:96 arg1 Epitopes 113:120 Crown Neutralization Epitopes 92:120 Crown Neutralization Epitopes 92:120 Short Communication: Manα1-2Man-Binding Anti-HIV Lectins Enhance the Exposure of V2i and V3 Crown Neutralization Epitopes on the V1/V2 and V3 Hypervariable Loops of HIV-1 Envelope. 28322582 0 8 theme V3 89:90 arg1 Exposure 69:76 the Exposure 65:76 the Exposure of V2i and V3 Crown Neutralization Epitopes 65:120 Short Communication: Manα1-2Man-Binding Anti-HIV Lectins Enhance the Exposure of V2i and V3 Crown Neutralization Epitopes on the V1/V2 and V3 Hypervariable Loops of HIV-1 Envelope. 28322582 1 9 theme hypervariable 317:329 arg1 loops 331:335 the hypervariable loops 313:335 the hypervariable loops of most exposed distal surface of HIV-1 Env 313:379 This study aimed to explore the contribution of high-mannose glycans in the masking of conserved V3 crown (GPG) and V2i epitopes on the hypervariable loops of most exposed distal surface of HIV-1 Env. 28322582 2 10 theme neutralization 641:654 arg1 strength 656:663 the neutralization strength 637:663 the neutralization strength of antibodies against these epitopes 637:700 Using lectins specific to Manα1-2Man residue containing Man6-9GlcNAc2 glycans extensively decorating HIV-1 Env, we found that Manα1-2Man-binding lectins enhance the exposure of these partially and transiently exposed epitopes and consequentially increase the neutralization strength of antibodies against these epitopes. 28322582 0 11 theme Neutralization 98:111 arg1 Epitopes 113:120 Crown Neutralization Epitopes 92:120 Crown Neutralization Epitopes 92:120 Short Communication: Manα1-2Man-Binding Anti-HIV Lectins Enhance the Exposure of V2i and V3 Crown Neutralization Epitopes on the V1/V2 and V3 Hypervariable Loops of HIV-1 Envelope. 28322582 2 12 theme Manα1-2Man 408:417 arg1 glycans 452:458 Manα1-2Man residue containing Man6-9GlcNAc2 glycans 408:458 Manα1-2Man residue containing Man6-9GlcNAc2 glycans extensively decorating HIV-1 Env 408:491 Using lectins specific to Manα1-2Man residue containing Man6-9GlcNAc2 glycans extensively decorating HIV-1 Env, we found that Manα1-2Man-binding lectins enhance the exposure of these partially and transiently exposed epitopes and consequentially increase the neutralization strength of antibodies against these epitopes. 28322582 0 13 theme Short 0:4 arg1 Communication 6:18 Short Communication 0:18 Short Communication: Manα1-2Man-Binding Anti-HIV Lectins Enhance the Exposure of V2i and V3 Crown Neutralization Epitopes on the V1/V2 and V3 Hypervariable Loops of HIV-1 Envelope. 0:179 Short Communication: Manα1-2Man-Binding Anti-HIV Lectins Enhance the Exposure of V2i and V3 Crown Neutralization Epitopes on the V1/V2 and V3 Hypervariable Loops of HIV-1 Envelope. 28322582 0 14 dep V2i 81:83 arg1 Epitopes 113:120 Crown Neutralization Epitopes 92:120 Crown Neutralization Epitopes 92:120 Short Communication: Manα1-2Man-Binding Anti-HIV Lectins Enhance the Exposure of V2i and V3 Crown Neutralization Epitopes on the V1/V2 and V3 Hypervariable Loops of HIV-1 Envelope. 28322582 2 15 theme exposed 591:597 arg1 epitopes 599:606 these partially and transiently exposed epitopes 559:606 these partially and transiently exposed epitopes 559:606 Using lectins specific to Manα1-2Man residue containing Man6-9GlcNAc2 glycans extensively decorating HIV-1 Env, we found that Manα1-2Man-binding lectins enhance the exposure of these partially and transiently exposed epitopes and consequentially increase the neutralization strength of antibodies against these epitopes. 28322582 0 16 theme Manα1-2Man-Binding 21:38 arg1 Lectins 49:55 Manα1-2Man-Binding Anti-HIV Lectins 21:55 Manα1-2Man-Binding Anti-HIV Lectins 21:55 Short Communication: Manα1-2Man-Binding Anti-HIV Lectins Enhance the Exposure of V2i and V3 Crown Neutralization Epitopes on the V1/V2 and V3 Hypervariable Loops of HIV-1 Envelope. 28322582 1 17 theme conserved 268:276 arg1 epitopes 301:308 conserved V3 crown (GPG) and V2i epitopes 268:308 conserved V3 crown (GPG) and V2i epitopes on the hypervariable loops of most exposed distal surface of HIV-1 Env 268:379 This study aimed to explore the contribution of high-mannose glycans in the masking of conserved V3 crown (GPG) and V2i epitopes on the hypervariable loops of most exposed distal surface of HIV-1 Env. 28322582 1 18 from loops 331:335 arg1 masking 257:263 the masking 253:263 the masking of conserved V3 crown (GPG) and V2i epitopes on the hypervariable loops of most exposed distal surface of HIV-1 Env 253:379 This study aimed to explore the contribution of high-mannose glycans in the masking of conserved V3 crown (GPG) and V2i epitopes on the hypervariable loops of most exposed distal surface of HIV-1 Env. 28322582 1 19 theme V3 278:279 arg1 GPG 288:290 GPG 288:290 GPG 288:290 This study aimed to explore the contribution of high-mannose glycans in the masking of conserved V3 crown (GPG) and V2i epitopes on the hypervariable loops of most exposed distal surface of HIV-1 Env. 28322582 1 19 theme V3 278:279 arg1 crown 281:285 V3 crown 278:285 V3 crown (GPG) 278:291 This study aimed to explore the contribution of high-mannose glycans in the masking of conserved V3 crown (GPG) and V2i epitopes on the hypervariable loops of most exposed distal surface of HIV-1 Env. 28322582 1 20 from masking 257:263 arg1 loops 331:335 the hypervariable loops 313:335 the hypervariable loops of most exposed distal surface of HIV-1 Env 313:379 This study aimed to explore the contribution of high-mannose glycans in the masking of conserved V3 crown (GPG) and V2i epitopes on the hypervariable loops of most exposed distal surface of HIV-1 Env. 28322582 1 21 theme exposed 345:351 arg1 surface 360:366 most exposed distal surface 340:366 most exposed distal surface of HIV-1 Env 340:379 This study aimed to explore the contribution of high-mannose glycans in the masking of conserved V3 crown (GPG) and V2i epitopes on the hypervariable loops of most exposed distal surface of HIV-1 Env. 28322582 1 22 theme crown 281:285 arg1 epitopes 301:308 conserved V3 crown (GPG) and V2i epitopes 268:308 conserved V3 crown (GPG) and V2i epitopes on the hypervariable loops of most exposed distal surface of HIV-1 Env 268:379 This study aimed to explore the contribution of high-mannose glycans in the masking of conserved V3 crown (GPG) and V2i epitopes on the hypervariable loops of most exposed distal surface of HIV-1 Env. 28322582 1 23 theme distal 353:358 arg1 surface 360:366 most exposed distal surface 340:366 most exposed distal surface of HIV-1 Env 340:379 This study aimed to explore the contribution of high-mannose glycans in the masking of conserved V3 crown (GPG) and V2i epitopes on the hypervariable loops of most exposed distal surface of HIV-1 Env. 28322582 0 24 theme Anti-HIV 40:47 arg1 Lectins 49:55 Manα1-2Man-Binding Anti-HIV Lectins 21:55 Manα1-2Man-Binding Anti-HIV Lectins 21:55 Short Communication: Manα1-2Man-Binding Anti-HIV Lectins Enhance the Exposure of V2i and V3 Crown Neutralization Epitopes on the V1/V2 and V3 Hypervariable Loops of HIV-1 Envelope. 28322582 2 25 theme Man6-9GlcNAc2 438:450 arg1 glycans 452:458 Manα1-2Man residue containing Man6-9GlcNAc2 glycans 408:458 Manα1-2Man residue containing Man6-9GlcNAc2 glycans extensively decorating HIV-1 Env 408:491 Using lectins specific to Manα1-2Man residue containing Man6-9GlcNAc2 glycans extensively decorating HIV-1 Env, we found that Manα1-2Man-binding lectins enhance the exposure of these partially and transiently exposed epitopes and consequentially increase the neutralization strength of antibodies against these epitopes. 28322582 1 26 theme surface 360:366 arg1 loops 331:335 the hypervariable loops 313:335 the hypervariable loops of most exposed distal surface of HIV-1 Env 313:379 This study aimed to explore the contribution of high-mannose glycans in the masking of conserved V3 crown (GPG) and V2i epitopes on the hypervariable loops of most exposed distal surface of HIV-1 Env. 28322582 2 27 theme specific 396:403 arg1 lectins 388:394 lectins 388:394 lectins specific to Manα1-2Man residue containing Man6-9GlcNAc2 glycans extensively decorating HIV-1 Env 388:491 Using lectins specific to Manα1-2Man residue containing Man6-9GlcNAc2 glycans extensively decorating HIV-1 Env, we found that Manα1-2Man-binding lectins enhance the exposure of these partially and transiently exposed epitopes and consequentially increase the neutralization strength of antibodies against these epitopes. 28322582 2 28 theme Manα1-2Man-binding 508:525 arg1 lectins 527:533 Manα1-2Man-binding lectins 508:533 Manα1-2Man-binding lectins 508:533 Using lectins specific to Manα1-2Man residue containing Man6-9GlcNAc2 glycans extensively decorating HIV-1 Env, we found that Manα1-2Man-binding lectins enhance the exposure of these partially and transiently exposed epitopes and consequentially increase the neutralization strength of antibodies against these epitopes. 28322582 2 29 theme containing 427:436 arg1 glycans 452:458 Manα1-2Man residue containing Man6-9GlcNAc2 glycans 408:458 Manα1-2Man residue containing Man6-9GlcNAc2 glycans extensively decorating HIV-1 Env 408:491 Using lectins specific to Manα1-2Man residue containing Man6-9GlcNAc2 glycans extensively decorating HIV-1 Env, we found that Manα1-2Man-binding lectins enhance the exposure of these partially and transiently exposed epitopes and consequentially increase the neutralization strength of antibodies against these epitopes. 28322582 0 30 theme Hypervariable 142:154 arg1 Loops 156:160 V3 Hypervariable Loops 139:160 V3 Hypervariable Loops 139:160 Short Communication: Manα1-2Man-Binding Anti-HIV Lectins Enhance the Exposure of V2i and V3 Crown Neutralization Epitopes on the V1/V2 and V3 Hypervariable Loops of HIV-1 Envelope. 28322582 1 31 from epitopes 301:308 arg1 loops 331:335 the hypervariable loops 313:335 the hypervariable loops of most exposed distal surface of HIV-1 Env 313:379 This study aimed to explore the contribution of high-mannose glycans in the masking of conserved V3 crown (GPG) and V2i epitopes on the hypervariable loops of most exposed distal surface of HIV-1 Env. 28322582 0 32 theme V3 139:140 arg1 Loops 156:160 V3 Hypervariable Loops 139:160 V3 Hypervariable Loops 139:160 Short Communication: Manα1-2Man-Binding Anti-HIV Lectins Enhance the Exposure of V2i and V3 Crown Neutralization Epitopes on the V1/V2 and V3 Hypervariable Loops of HIV-1 Envelope. 28322582 1 33 theme HIV-1 371:375 arg1 Env 377:379 HIV-1 Env 371:379 HIV-1 Env 371:379 This study aimed to explore the contribution of high-mannose glycans in the masking of conserved V3 crown (GPG) and V2i epitopes on the hypervariable loops of most exposed distal surface of HIV-1 Env. 28322582 1 34 theme Env 377:379 arg1 surface 360:366 most exposed distal surface 340:366 most exposed distal surface of HIV-1 Env 340:379 This study aimed to explore the contribution of high-mannose glycans in the masking of conserved V3 crown (GPG) and V2i epitopes on the hypervariable loops of most exposed distal surface of HIV-1 Env. 28322582 1 35 from contribution 213:224 arg1 masking 257:263 the masking 253:263 the masking of conserved V3 crown (GPG) and V2i epitopes on the hypervariable loops of most exposed distal surface of HIV-1 Env 253:379 This study aimed to explore the contribution of high-mannose glycans in the masking of conserved V3 crown (GPG) and V2i epitopes on the hypervariable loops of most exposed distal surface of HIV-1 Env. 28322582 2 36 theme residue 419:425 arg1 glycans 452:458 Manα1-2Man residue containing Man6-9GlcNAc2 glycans 408:458 Manα1-2Man residue containing Man6-9GlcNAc2 glycans extensively decorating HIV-1 Env 408:491 Using lectins specific to Manα1-2Man residue containing Man6-9GlcNAc2 glycans extensively decorating HIV-1 Env, we found that Manα1-2Man-binding lectins enhance the exposure of these partially and transiently exposed epitopes and consequentially increase the neutralization strength of antibodies against these epitopes. 28322582 0 37 dep Communication 6:18 arg1 Enhance 57:63 Enhance 57:63 Enhance the Exposure of V2i and V3 Crown Neutralization Epitopes on the V1/V2 and V3 Hypervariable Loops of HIV-1 Envelope 57:178 Short Communication: Manα1-2Man-Binding Anti-HIV Lectins Enhance the Exposure of V2i and V3 Crown Neutralization Epitopes on the V1/V2 and V3 Hypervariable Loops of HIV-1 Envelope. 28322582 2 38 theme HIV-1 483:487 arg1 Env 489:491 HIV-1 Env 483:491 HIV-1 Env 483:491 Using lectins specific to Manα1-2Man residue containing Man6-9GlcNAc2 glycans extensively decorating HIV-1 Env, we found that Manα1-2Man-binding lectins enhance the exposure of these partially and transiently exposed epitopes and consequentially increase the neutralization strength of antibodies against these epitopes. 28322582 1 39 theme V2i 297:299 arg1 epitopes 301:308 conserved V3 crown (GPG) and V2i epitopes 268:308 conserved V3 crown (GPG) and V2i epitopes on the hypervariable loops of most exposed distal surface of HIV-1 Env 268:379 This study aimed to explore the contribution of high-mannose glycans in the masking of conserved V3 crown (GPG) and V2i epitopes on the hypervariable loops of most exposed distal surface of HIV-1 Env. 28322582 0 40 dep V1/V2 129:133 arg1 the 125:127 the 125:127 the 125:127 Short Communication: Manα1-2Man-Binding Anti-HIV Lectins Enhance the Exposure of V2i and V3 Crown Neutralization Epitopes on the V1/V2 and V3 Hypervariable Loops of HIV-1 Envelope. 28322582 1 41 theme high-mannose 229:240 arg1 glycans 242:248 high-mannose glycans 229:248 high-mannose glycans 229:248 This study aimed to explore the contribution of high-mannose glycans in the masking of conserved V3 crown (GPG) and V2i epitopes on the hypervariable loops of most exposed distal surface of HIV-1 Env. 27123103 0 0 theme signaling-enhancing 93:111 arg1 activity 113:120 Wnt/β-catenin signaling-enhancing activity 79:120 Wnt/β-catenin signaling-enhancing activity 79:120 N-glycosylation of R-spondin1 at Asn137 negatively regulates its secretion and Wnt/β-catenin signaling-enhancing activity. 27123103 9 1 theme signaling-enhancing 1321:1339 arg1 effect 1341:1346 Wnt/β-catenin signaling-enhancing effect 1307:1346 Wnt/β-catenin signaling-enhancing effect of RSPO1 1307:1355 The role of N-glycosylation in RSPO1 was evaluated by conducting comparative experiments with wt and N137Q RSPO1, which revealed that the N137Q mutant increased the secretion and Wnt/β-catenin signaling-enhancing effect of RSPO1, compared with wt RSPO1. 27123103 8 2 theme Wnt/β-catenin 1035:1047 arg1 activity 1069:1076 Wnt/β-catenin signaling-enhancing activity 1035:1076 Wnt/β-catenin signaling-enhancing activity 1035:1076 RSPO1 is a secreted protein that has Wnt/β-catenin signaling-enhancing activity and is expected to have therapeutic applications. 27123103 8 3 theme secreted 1009:1016 arg1 RSPO1 998:1002 RSPO1 998:1002 RSPO1 998:1002 RSPO1 is a secreted protein that has Wnt/β-catenin signaling-enhancing activity and is expected to have therapeutic applications. 27123103 8 3 theme secreted 1009:1016 arg1 protein 1018:1024 a secreted protein 1007:1024 a secreted protein that has Wnt/β-catenin signaling-enhancing activity and is expected to have therapeutic applications 1007:1125 RSPO1 is a secreted protein that has Wnt/β-catenin signaling-enhancing activity and is expected to have therapeutic applications. 27123103 1 4 theme wide 191:194 arg1 functions 207:215 functions 207:215 functions 207:215 N-glycosylation is a post-translational protein modification with a wide variety of functions. 27123103 1 4 theme wide 191:194 arg1 variety 196:202 a wide variety 189:202 a wide variety of functions 189:215 N-glycosylation is a post-translational protein modification with a wide variety of functions. 27123103 4 5 dep In 503:504 arg1 vitro 506:510 vitro 506:510 vitro 506:510 In vitro treatment with peptide-N-glycosidase F increased the electrophoretic mobility of RSPO1. 27123103 0 6 theme Wnt/β-catenin 79:91 arg1 activity 113:120 Wnt/β-catenin signaling-enhancing activity 79:120 Wnt/β-catenin signaling-enhancing activity 79:120 N-glycosylation of R-spondin1 at Asn137 negatively regulates its secretion and Wnt/β-catenin signaling-enhancing activity. 27123103 4 7 theme electrophoretic 565:579 arg1 mobility 581:588 the electrophoretic mobility 561:588 the electrophoretic mobility of RSPO1 561:597 In vitro treatment with peptide-N-glycosidase F increased the electrophoretic mobility of RSPO1. 27123103 10 8 theme Wnt/β-catenin 1480:1492 arg1 effect 1514:1519 Wnt/β-catenin signaling-enhancing effect 1480:1519 Wnt/β-catenin signaling-enhancing effect 1480:1519 These results suggest that N-glycosylation of RSPO1 has a negative influence on its secretion and Wnt/β-catenin signaling-enhancing effect. 27123103 5 9 theme RSPO1-overexpressing 641:660 arg1 cells 669:673 wild-type (wt) RSPO1-overexpressing HT1080 cells 626:673 wild-type (wt) RSPO1-overexpressing HT1080 cells 626:673 Furthermore, treatment of wild-type (wt) RSPO1-overexpressing HT1080 cells with tunicamycin (TM), which inhibits N-glycosylation, resulted in a significant reduction in the molecular weight of RSPO1. 27123103 5 10 dep wild-type 626:634 arg1 wt 637:638 wt 637:638 wt 637:638 Furthermore, treatment of wild-type (wt) RSPO1-overexpressing HT1080 cells with tunicamycin (TM), which inhibits N-glycosylation, resulted in a significant reduction in the molecular weight of RSPO1. 27123103 7 11 gly N-glycosylated 972:985 arg2 Asn137 990:995 Asn137 990:995 Asn137 990:995 These results demonstrated for the first time that RSPO1 is N-glycosylated at Asn137. 27123103 7 11 gly N-glycosylated 972:985 arg1 RSPO1 963:967 RSPO1 963:967 RSPO1 963:967 These results demonstrated for the first time that RSPO1 is N-glycosylated at Asn137. 27123103 5 12 theme molecular 773:781 arg1 weight 783:788 the molecular weight 769:788 the molecular weight of RSPO1 769:797 Furthermore, treatment of wild-type (wt) RSPO1-overexpressing HT1080 cells with tunicamycin (TM), which inhibits N-glycosylation, resulted in a significant reduction in the molecular weight of RSPO1. 27123103 3 13 from secretion 444:452 arg1 signaling 492:500 Wnt/β-catenin signaling 478:500 Wnt/β-catenin signaling 478:500 The present study identified that RSPO1 was N-glycosylated at Asn137, and that N-glycosylation of RSPO1 negatively influenced its secretion and enhancing effect on Wnt/β-catenin signaling. 27123103 5 14 theme HT1080 662:667 arg1 cells 669:673 wild-type (wt) RSPO1-overexpressing HT1080 cells 626:673 wild-type (wt) RSPO1-overexpressing HT1080 cells 626:673 Furthermore, treatment of wild-type (wt) RSPO1-overexpressing HT1080 cells with tunicamycin (TM), which inhibits N-glycosylation, resulted in a significant reduction in the molecular weight of RSPO1. 27123103 6 15 contain had 822:824 arg1 treatment 812:820 TM treatment 809:820 TM treatment 809:820 However, TM treatment had no effect in the RSPO1 mutant whereby the Asn137 residue was replaced by Gln (N137Q). 27123103 6 15 contain had 822:824 arg2 effect 829:834 no effect 826:834 no effect 826:834 However, TM treatment had no effect in the RSPO1 mutant whereby the Asn137 residue was replaced by Gln (N137Q). 27123103 9 16 theme RSPO1 1351:1355 arg1 effect 1341:1346 Wnt/β-catenin signaling-enhancing effect 1307:1346 Wnt/β-catenin signaling-enhancing effect of RSPO1 1307:1355 The role of N-glycosylation in RSPO1 was evaluated by conducting comparative experiments with wt and N137Q RSPO1, which revealed that the N137Q mutant increased the secretion and Wnt/β-catenin signaling-enhancing effect of RSPO1, compared with wt RSPO1. 27123103 9 16 theme RSPO1 1351:1355 arg1 secretion 1293:1301 the secretion 1289:1301 the secretion 1289:1301 The role of N-glycosylation in RSPO1 was evaluated by conducting comparative experiments with wt and N137Q RSPO1, which revealed that the N137Q mutant increased the secretion and Wnt/β-catenin signaling-enhancing effect of RSPO1, compared with wt RSPO1. 27123103 8 17 theme signaling-enhancing 1049:1067 arg1 activity 1069:1076 Wnt/β-catenin signaling-enhancing activity 1035:1076 Wnt/β-catenin signaling-enhancing activity 1035:1076 RSPO1 is a secreted protein that has Wnt/β-catenin signaling-enhancing activity and is expected to have therapeutic applications. 27123103 5 18 theme cells 669:673 arg1 treatment 613:621 treatment 613:621 treatment of wild-type (wt) RSPO1-overexpressing HT1080 cells with tunicamycin (TM), which inhibits N-glycosylation, 613:728 Furthermore, treatment of wild-type (wt) RSPO1-overexpressing HT1080 cells with tunicamycin (TM), which inhibits N-glycosylation, resulted in a significant reduction in the molecular weight of RSPO1. 27123103 4 19 with treatment 512:520 arg1 F 549:549 peptide-N-glycosidase F 527:549 peptide-N-glycosidase F 527:549 In vitro treatment with peptide-N-glycosidase F increased the electrophoretic mobility of RSPO1. 27123103 5 20 from reduction 756:764 arg1 weight 783:788 the molecular weight 769:788 the molecular weight of RSPO1 769:797 Furthermore, treatment of wild-type (wt) RSPO1-overexpressing HT1080 cells with tunicamycin (TM), which inhibits N-glycosylation, resulted in a significant reduction in the molecular weight of RSPO1. 27123103 9 21 theme N137Q 1229:1233 arg1 RSPO1 1235:1239 N137Q RSPO1 1229:1239 N137Q RSPO1 1229:1239 The role of N-glycosylation in RSPO1 was evaluated by conducting comparative experiments with wt and N137Q RSPO1, which revealed that the N137Q mutant increased the secretion and Wnt/β-catenin signaling-enhancing effect of RSPO1, compared with wt RSPO1. 27123103 7 22 from Asn137 990:995 arg1 N-glycosylated 972:985 N-glycosylated 972:985 N-glycosylated 972:985 These results demonstrated for the first time that RSPO1 is N-glycosylated at Asn137. 27123103 5 23 theme RSPO1 793:797 arg1 weight 783:788 the molecular weight 769:788 the molecular weight of RSPO1 769:797 Furthermore, treatment of wild-type (wt) RSPO1-overexpressing HT1080 cells with tunicamycin (TM), which inhibits N-glycosylation, resulted in a significant reduction in the molecular weight of RSPO1. 27123103 4 24 theme peptide-N-glycosidase 527:547 arg1 F 549:549 peptide-N-glycosidase F 527:549 peptide-N-glycosidase F 527:549 In vitro treatment with peptide-N-glycosidase F increased the electrophoretic mobility of RSPO1. 27123103 1 25 with modification 171:182 arg1 functions 207:215 functions 207:215 functions 207:215 N-glycosylation is a post-translational protein modification with a wide variety of functions. 27123103 1 25 with modification 171:182 arg1 variety 196:202 a wide variety 189:202 a wide variety of functions 189:215 N-glycosylation is a post-translational protein modification with a wide variety of functions. 27123103 5 26 theme wild-type 626:634 arg1 cells 669:673 wild-type (wt) RSPO1-overexpressing HT1080 cells 626:673 wild-type (wt) RSPO1-overexpressing HT1080 cells 626:673 Furthermore, treatment of wild-type (wt) RSPO1-overexpressing HT1080 cells with tunicamycin (TM), which inhibits N-glycosylation, resulted in a significant reduction in the molecular weight of RSPO1. 27123103 9 27 theme N137Q 1266:1270 arg1 mutant 1272:1277 the N137Q mutant 1262:1277 the N137Q mutant 1262:1277 The role of N-glycosylation in RSPO1 was evaluated by conducting comparative experiments with wt and N137Q RSPO1, which revealed that the N137Q mutant increased the secretion and Wnt/β-catenin signaling-enhancing effect of RSPO1, compared with wt RSPO1. 27123103 1 28 theme functions 207:215 arg1 functions 207:215 functions 207:215 functions 207:215 N-glycosylation is a post-translational protein modification with a wide variety of functions. 27123103 1 28 theme functions 207:215 arg1 variety 196:202 a wide variety 189:202 a wide variety of functions 189:215 N-glycosylation is a post-translational protein modification with a wide variety of functions. 27123103 0 29 from Asn137 33:38 arg1 N-glycosylation 0:14 N-glycosylation 0:14 N-glycosylation of R-spondin1 at Asn137 0:38 N-glycosylation of R-spondin1 at Asn137 negatively regulates its secretion and Wnt/β-catenin signaling-enhancing activity. 27123103 3 30 gly N-glycosylation 393:407 arg1 RSPO1 412:416 RSPO1 412:416 RSPO1 412:416 The present study identified that RSPO1 was N-glycosylated at Asn137, and that N-glycosylation of RSPO1 negatively influenced its secretion and enhancing effect on Wnt/β-catenin signaling. 27123103 3 31 theme RSPO1 412:416 arg1 N-glycosylation 393:407 N-glycosylation 393:407 N-glycosylation of RSPO1 393:416 The present study identified that RSPO1 was N-glycosylated at Asn137, and that N-glycosylation of RSPO1 negatively influenced its secretion and enhancing effect on Wnt/β-catenin signaling. 27123103 9 32 theme wt 1372:1373 arg1 RSPO1 1375:1379 wt RSPO1 1372:1379 wt RSPO1 1372:1379 The role of N-glycosylation in RSPO1 was evaluated by conducting comparative experiments with wt and N137Q RSPO1, which revealed that the N137Q mutant increased the secretion and Wnt/β-catenin signaling-enhancing effect of RSPO1, compared with wt RSPO1. 27123103 10 33 theme RSPO1 1428:1432 arg1 N-glycosylation 1409:1423 N-glycosylation 1409:1423 N-glycosylation of RSPO1 1409:1432 These results suggest that N-glycosylation of RSPO1 has a negative influence on its secretion and Wnt/β-catenin signaling-enhancing effect. 27123103 3 34 theme enhancing 458:466 arg1 effect 468:473 enhancing effect 458:473 enhancing effect on Wnt/β-catenin signaling 458:500 The present study identified that RSPO1 was N-glycosylated at Asn137, and that N-glycosylation of RSPO1 negatively influenced its secretion and enhancing effect on Wnt/β-catenin signaling. 27123103 5 35 theme significant 744:754 arg1 reduction 756:764 a significant reduction 742:764 a significant reduction in the molecular weight of RSPO1 742:797 Furthermore, treatment of wild-type (wt) RSPO1-overexpressing HT1080 cells with tunicamycin (TM), which inhibits N-glycosylation, resulted in a significant reduction in the molecular weight of RSPO1. 27123103 7 36 theme first 947:951 arg1 time 953:956 the first time 943:956 the first time 943:956 These results demonstrated for the first time that RSPO1 is N-glycosylated at Asn137. 27123103 10 37 theme negative 1440:1447 arg1 influence 1449:1457 a negative influence 1438:1457 a negative influence 1438:1457 These results suggest that N-glycosylation of RSPO1 has a negative influence on its secretion and Wnt/β-catenin signaling-enhancing effect. 27123103 2 38 gly N-glycosylated 267:280 arg1 RSPO1 257:261 RSPO1 257:261 RSPO1 257:261 It has been predicted that R-spondin1 (RSPO1) is N-glycosylated, although this remains unknown. 27123103 2 38 gly N-glycosylated 267:280 arg1 R-spondin1 245:254 R-spondin1 245:254 R-spondin1 (RSPO1) 245:262 It has been predicted that R-spondin1 (RSPO1) is N-glycosylated, although this remains unknown. 27123103 8 39 contain have 1097:1100 arg1 RSPO1 998:1002 RSPO1 998:1002 RSPO1 998:1002 RSPO1 is a secreted protein that has Wnt/β-catenin signaling-enhancing activity and is expected to have therapeutic applications. 27123103 8 39 contain have 1097:1100 arg1 protein 1018:1024 a secreted protein 1007:1024 a secreted protein that has Wnt/β-catenin signaling-enhancing activity and is expected to have therapeutic applications 1007:1125 RSPO1 is a secreted protein that has Wnt/β-catenin signaling-enhancing activity and is expected to have therapeutic applications. 27123103 8 39 contain have 1097:1100 arg2 applications 1114:1125 therapeutic applications 1102:1125 therapeutic applications 1102:1125 RSPO1 is a secreted protein that has Wnt/β-catenin signaling-enhancing activity and is expected to have therapeutic applications. 27123103 3 40 from Asn137 376:381 arg1 N-glycosylated 358:371 N-glycosylated 358:371 N-glycosylated 358:371 The present study identified that RSPO1 was N-glycosylated at Asn137, and that N-glycosylation of RSPO1 negatively influenced its secretion and enhancing effect on Wnt/β-catenin signaling. 27123103 0 41 gly N-glycosylation 0:14 arg1 R-spondin1 19:28 R-spondin1 19:28 R-spondin1 19:28 N-glycosylation of R-spondin1 at Asn137 negatively regulates its secretion and Wnt/β-catenin signaling-enhancing activity. 27123103 0 41 gly N-glycosylation 0:14 arg2 Asn137 33:38 Asn137 33:38 Asn137 33:38 N-glycosylation of R-spondin1 at Asn137 negatively regulates its secretion and Wnt/β-catenin signaling-enhancing activity. 27123103 0 41 gly N-glycosylation 0:14 arg1 Asn137 33:38 Asn137 33:38 Asn137 33:38 N-glycosylation of R-spondin1 at Asn137 negatively regulates its secretion and Wnt/β-catenin signaling-enhancing activity. 27123103 9 42 theme N-glycosylation 1140:1154 arg1 role 1132:1135 The role 1128:1135 The role of N-glycosylation in RSPO1 1128:1163 The role of N-glycosylation in RSPO1 was evaluated by conducting comparative experiments with wt and N137Q RSPO1, which revealed that the N137Q mutant increased the secretion and Wnt/β-catenin signaling-enhancing effect of RSPO1, compared with wt RSPO1. 27123103 3 43 theme Wnt/β-catenin 478:490 arg1 signaling 492:500 Wnt/β-catenin signaling 478:500 Wnt/β-catenin signaling 478:500 The present study identified that RSPO1 was N-glycosylated at Asn137, and that N-glycosylation of RSPO1 negatively influenced its secretion and enhancing effect on Wnt/β-catenin signaling. 27123103 4 44 theme In 503:504 arg1 treatment 512:520 In vitro treatment 503:520 In vitro treatment with peptide-N-glycosidase F 503:549 In vitro treatment with peptide-N-glycosidase F increased the electrophoretic mobility of RSPO1. 27123103 6 45 theme TM 809:810 arg1 treatment 812:820 TM treatment 809:820 TM treatment 809:820 However, TM treatment had no effect in the RSPO1 mutant whereby the Asn137 residue was replaced by Gln (N137Q). 27123103 3 46 gly N-glycosylated 358:371 arg2 Asn137 376:381 Asn137 376:381 Asn137 376:381 The present study identified that RSPO1 was N-glycosylated at Asn137, and that N-glycosylation of RSPO1 negatively influenced its secretion and enhancing effect on Wnt/β-catenin signaling. 27123103 3 46 gly N-glycosylated 358:371 arg1 RSPO1 348:352 RSPO1 348:352 RSPO1 348:352 The present study identified that RSPO1 was N-glycosylated at Asn137, and that N-glycosylation of RSPO1 negatively influenced its secretion and enhancing effect on Wnt/β-catenin signaling. 27123103 8 47 theme therapeutic 1102:1112 arg1 applications 1114:1125 therapeutic applications 1102:1125 therapeutic applications 1102:1125 RSPO1 is a secreted protein that has Wnt/β-catenin signaling-enhancing activity and is expected to have therapeutic applications. 27123103 9 48 from role 1132:1135 arg1 RSPO1 1159:1163 RSPO1 1159:1163 RSPO1 1159:1163 The role of N-glycosylation in RSPO1 was evaluated by conducting comparative experiments with wt and N137Q RSPO1, which revealed that the N137Q mutant increased the secretion and Wnt/β-catenin signaling-enhancing effect of RSPO1, compared with wt RSPO1. 27123103 1 49 theme post-translational 144:161 arg1 modification 171:182 a post-translational protein modification 142:182 a post-translational protein modification with a wide variety of functions 142:215 N-glycosylation is a post-translational protein modification with a wide variety of functions. 27123103 1 49 theme post-translational 144:161 arg1 N-glycosylation 123:137 N-glycosylation 123:137 N-glycosylation 123:137 N-glycosylation is a post-translational protein modification with a wide variety of functions. 27123103 4 50 theme RSPO1 593:597 arg1 mobility 581:588 the electrophoretic mobility 561:588 the electrophoretic mobility of RSPO1 561:597 In vitro treatment with peptide-N-glycosidase F increased the electrophoretic mobility of RSPO1. 27123103 6 51 theme Asn137 868:873 arg1 residue 875:881 the Asn137 residue 864:881 the Asn137 residue 864:881 However, TM treatment had no effect in the RSPO1 mutant whereby the Asn137 residue was replaced by Gln (N137Q). 27123103 6 52 theme RSPO1 843:847 arg1 mutant 849:854 the RSPO1 mutant 839:854 the RSPO1 mutant whereby the Asn137 residue was replaced by Gln (N137Q) 839:909 However, TM treatment had no effect in the RSPO1 mutant whereby the Asn137 residue was replaced by Gln (N137Q). 27123103 1 53 theme protein 163:169 arg1 modification 171:182 a post-translational protein modification 142:182 a post-translational protein modification with a wide variety of functions 142:215 N-glycosylation is a post-translational protein modification with a wide variety of functions. 27123103 1 53 theme protein 163:169 arg1 N-glycosylation 123:137 N-glycosylation 123:137 N-glycosylation 123:137 N-glycosylation is a post-translational protein modification with a wide variety of functions. 27123103 9 54 theme comparative 1193:1203 arg1 experiments 1205:1215 comparative experiments 1193:1215 comparative experiments with wt and N137Q RSPO1, which revealed that the N137Q mutant increased the secretion and Wnt/β-catenin signaling-enhancing effect of RSPO1, compared with wt RSPO1 1193:1379 The role of N-glycosylation in RSPO1 was evaluated by conducting comparative experiments with wt and N137Q RSPO1, which revealed that the N137Q mutant increased the secretion and Wnt/β-catenin signaling-enhancing effect of RSPO1, compared with wt RSPO1. 27123103 3 55 theme present 318:324 arg1 study 326:330 The present study 314:330 The present study 314:330 The present study identified that RSPO1 was N-glycosylated at Asn137, and that N-glycosylation of RSPO1 negatively influenced its secretion and enhancing effect on Wnt/β-catenin signaling. 27123103 9 56 with experiments 1205:1215 arg1 wt 1222:1223 wt 1222:1223 wt 1222:1223 The role of N-glycosylation in RSPO1 was evaluated by conducting comparative experiments with wt and N137Q RSPO1, which revealed that the N137Q mutant increased the secretion and Wnt/β-catenin signaling-enhancing effect of RSPO1, compared with wt RSPO1. 27123103 9 56 with experiments 1205:1215 arg1 RSPO1 1235:1239 N137Q RSPO1 1229:1239 N137Q RSPO1 1229:1239 The role of N-glycosylation in RSPO1 was evaluated by conducting comparative experiments with wt and N137Q RSPO1, which revealed that the N137Q mutant increased the secretion and Wnt/β-catenin signaling-enhancing effect of RSPO1, compared with wt RSPO1. 27123103 8 57 contain has 1031:1033 arg1 RSPO1 998:1002 RSPO1 998:1002 RSPO1 998:1002 RSPO1 is a secreted protein that has Wnt/β-catenin signaling-enhancing activity and is expected to have therapeutic applications. 27123103 8 57 contain has 1031:1033 arg2 activity 1069:1076 Wnt/β-catenin signaling-enhancing activity 1035:1076 Wnt/β-catenin signaling-enhancing activity 1035:1076 RSPO1 is a secreted protein that has Wnt/β-catenin signaling-enhancing activity and is expected to have therapeutic applications. 27123103 8 57 contain has 1031:1033 arg1 protein 1018:1024 a secreted protein 1007:1024 a secreted protein that has Wnt/β-catenin signaling-enhancing activity and is expected to have therapeutic applications 1007:1125 RSPO1 is a secreted protein that has Wnt/β-catenin signaling-enhancing activity and is expected to have therapeutic applications. 27123103 5 58 with treatment 613:621 arg1 TM 693:694 TM 693:694 TM 693:694 Furthermore, treatment of wild-type (wt) RSPO1-overexpressing HT1080 cells with tunicamycin (TM), which inhibits N-glycosylation, resulted in a significant reduction in the molecular weight of RSPO1. 27123103 5 58 with treatment 613:621 arg1 tunicamycin 680:690 tunicamycin 680:690 tunicamycin (TM) 680:695 Furthermore, treatment of wild-type (wt) RSPO1-overexpressing HT1080 cells with tunicamycin (TM), which inhibits N-glycosylation, resulted in a significant reduction in the molecular weight of RSPO1. 27123103 10 59 contain has 1434:1436 arg2 influence 1449:1457 a negative influence 1438:1457 a negative influence 1438:1457 These results suggest that N-glycosylation of RSPO1 has a negative influence on its secretion and Wnt/β-catenin signaling-enhancing effect. 27123103 10 59 contain has 1434:1436 arg1 N-glycosylation 1409:1423 N-glycosylation 1409:1423 N-glycosylation of RSPO1 1409:1432 These results suggest that N-glycosylation of RSPO1 has a negative influence on its secretion and Wnt/β-catenin signaling-enhancing effect. 27123103 10 60 gly N-glycosylation 1409:1423 arg1 RSPO1 1428:1432 RSPO1 1428:1432 RSPO1 1428:1432 These results suggest that N-glycosylation of RSPO1 has a negative influence on its secretion and Wnt/β-catenin signaling-enhancing effect. 27123103 9 61 theme Wnt/β-catenin 1307:1319 arg1 effect 1341:1346 Wnt/β-catenin signaling-enhancing effect 1307:1346 Wnt/β-catenin signaling-enhancing effect of RSPO1 1307:1355 The role of N-glycosylation in RSPO1 was evaluated by conducting comparative experiments with wt and N137Q RSPO1, which revealed that the N137Q mutant increased the secretion and Wnt/β-catenin signaling-enhancing effect of RSPO1, compared with wt RSPO1. 27123103 0 62 theme R-spondin1 19:28 arg1 N-glycosylation 0:14 N-glycosylation 0:14 N-glycosylation of R-spondin1 at Asn137 0:38 N-glycosylation of R-spondin1 at Asn137 negatively regulates its secretion and Wnt/β-catenin signaling-enhancing activity. 27123103 3 63 from effect 468:473 arg1 signaling 492:500 Wnt/β-catenin signaling 478:500 Wnt/β-catenin signaling 478:500 The present study identified that RSPO1 was N-glycosylated at Asn137, and that N-glycosylation of RSPO1 negatively influenced its secretion and enhancing effect on Wnt/β-catenin signaling. 27123103 10 64 theme signaling-enhancing 1494:1512 arg1 effect 1514:1519 Wnt/β-catenin signaling-enhancing effect 1480:1519 Wnt/β-catenin signaling-enhancing effect 1480:1519 These results suggest that N-glycosylation of RSPO1 has a negative influence on its secretion and Wnt/β-catenin signaling-enhancing effect. 32625482 1 0 theme polysaccharide 304:317 arg1 complex 319:325 alginate-konjac-xanthan polysaccharide complex 280:325 alginate-konjac-xanthan polysaccharide complex (PGX) 280:331 Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver a scientific opinion on alginate-konjac-xanthan polysaccharide complex (PGX) as a novel food (NF) submitted pursuant to Regulation (EC) No 258/97. 32625482 1 0 theme polysaccharide 304:317 arg1 PGX 328:330 PGX 328:330 PGX 328:330 Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver a scientific opinion on alginate-konjac-xanthan polysaccharide complex (PGX) as a novel food (NF) submitted pursuant to Regulation (EC) No 258/97. 32625482 1 1 from opinion 269:275 arg1 complex 319:325 alginate-konjac-xanthan polysaccharide complex 280:325 alginate-konjac-xanthan polysaccharide complex (PGX) 280:331 Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver a scientific opinion on alginate-konjac-xanthan polysaccharide complex (PGX) as a novel food (NF) submitted pursuant to Regulation (EC) No 258/97. 32625482 1 1 from opinion 269:275 arg1 PGX 328:330 PGX 328:330 PGX 328:330 Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver a scientific opinion on alginate-konjac-xanthan polysaccharide complex (PGX) as a novel food (NF) submitted pursuant to Regulation (EC) No 258/97. 32625482 6 2 from foods 981:985 arg1 intake 949:954 The recommended maximum daily intake 919:954 The recommended maximum daily intake of the NF from fortified foods and food supplements 919:1006 The recommended maximum daily intake of the NF from fortified foods and food supplements is 15 g. 32625482 6 2 from foods 981:985 arg1 15 g 1011:1014 15 g 1011:1014 15 g 1011:1014 The recommended maximum daily intake of the NF from fortified foods and food supplements is 15 g. 32625482 6 3 theme fortified 971:979 arg1 foods 981:985 fortified foods 971:985 fortified foods 971:985 The recommended maximum daily intake of the NF from fortified foods and food supplements is 15 g. 32625482 8 4 theme food 1411:1414 arg1 supplements 1416:1426 food supplements 1411:1426 food supplements 1411:1426 Considering the no observed adverse effect level of 1.8 g/kg body weight (bw) per day in a subchronic toxicity study with PGX and the highest mean and 95th percentile anticipated daily intake of NF from fortified foods, the margin of exposure (MoE) is 12 and 6, respectively, whereas the MoE for the NF from food supplements is 9. 32625482 0 5 theme novel 68:72 arg1 food 74:77 a novel food 66:77 a novel food pursuant to Regulation (EC) No 258/97 66:115 Safety of alginate-konjac-xanthan polysaccharide complex (PGX) as a novel food pursuant to Regulation (EC) No 258/97. 32625482 8 6 theme exposure 1337:1344 arg1 12 1355:1356 12 1355:1356 12 1355:1356 Considering the no observed adverse effect level of 1.8 g/kg body weight (bw) per day in a subchronic toxicity study with PGX and the highest mean and 95th percentile anticipated daily intake of NF from fortified foods, the margin of exposure (MoE) is 12 and 6, respectively, whereas the MoE for the NF from food supplements is 9. 32625482 8 6 theme exposure 1337:1344 arg1 margin 1327:1332 the margin 1323:1332 the margin of exposure (MoE) 1323:1350 Considering the no observed adverse effect level of 1.8 g/kg body weight (bw) per day in a subchronic toxicity study with PGX and the highest mean and 95th percentile anticipated daily intake of NF from fortified foods, the margin of exposure (MoE) is 12 and 6, respectively, whereas the MoE for the NF from food supplements is 9. 32625482 1 7 theme Regulation 376:385 arg1 No 258/97 392:400 Regulation (EC) No 258/97 376:400 Regulation (EC) No 258/97 376:400 Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver a scientific opinion on alginate-konjac-xanthan polysaccharide complex (PGX) as a novel food (NF) submitted pursuant to Regulation (EC) No 258/97. 32625482 7 8 from 18 1080:1081 arg1 population 1028:1037 The target population 1017:1037 The target population proposed by the applicant 1017:1063 The target population proposed by the applicant is adults from 18 to 64 years of age. 32625482 7 8 from 18 1080:1081 arg1 adults 1068:1073 adults 1068:1073 adults from 18 to 64 years of age 1068:1100 The target population proposed by the applicant is adults from 18 to 64 years of age. 32625482 8 9 from study 1214:1218 arg1 percentile 1259:1268 95th percentile 1254:1268 95th percentile 1254:1268 Considering the no observed adverse effect level of 1.8 g/kg body weight (bw) per day in a subchronic toxicity study with PGX and the highest mean and 95th percentile anticipated daily intake of NF from fortified foods, the margin of exposure (MoE) is 12 and 6, respectively, whereas the MoE for the NF from food supplements is 9. 32625482 8 9 from study 1214:1218 arg1 level 1146:1150 observed adverse effect level 1122:1150 observed adverse effect level of 1.8 g/kg body weight (bw) per day in a subchronic toxicity study with PGX and the highest mean 1122:1248 Considering the no observed adverse effect level of 1.8 g/kg body weight (bw) per day in a subchronic toxicity study with PGX and the highest mean and 95th percentile anticipated daily intake of NF from fortified foods, the margin of exposure (MoE) is 12 and 6, respectively, whereas the MoE for the NF from food supplements is 9. 32625482 2 10 dep polysaccharides 471:485 arg1 alginate 531:538 sodium alginate 524:538 sodium alginate 524:538 The NF is an off-white granular powder composed of three non-starch polysaccharides: konjac glucomannan, xanthan gum and sodium alginate. 32625482 2 10 dep polysaccharides 471:485 arg1 polysaccharides 471:485 three non-starch polysaccharides 454:485 three non-starch polysaccharides: konjac glucomannan, xanthan gum and sodium alginate 454:538 The NF is an off-white granular powder composed of three non-starch polysaccharides: konjac glucomannan, xanthan gum and sodium alginate. 32625482 2 10 dep polysaccharides 471:485 arg1 glucomannan 495:505 konjac glucomannan 488:505 konjac glucomannan 488:505 The NF is an off-white granular powder composed of three non-starch polysaccharides: konjac glucomannan, xanthan gum and sodium alginate. 32625482 2 10 dep polysaccharides 471:485 arg1 gum 516:518 xanthan gum 508:518 xanthan gum 508:518 The NF is an off-white granular powder composed of three non-starch polysaccharides: konjac glucomannan, xanthan gum and sodium alginate. 32625482 2 11 theme sodium 524:529 arg1 alginate 531:538 sodium alginate 524:538 sodium alginate 524:538 The NF is an off-white granular powder composed of three non-starch polysaccharides: konjac glucomannan, xanthan gum and sodium alginate. 32625482 2 11 theme sodium 524:529 arg1 polysaccharides 471:485 three non-starch polysaccharides 454:485 three non-starch polysaccharides: konjac glucomannan, xanthan gum and sodium alginate 454:538 The NF is an off-white granular powder composed of three non-starch polysaccharides: konjac glucomannan, xanthan gum and sodium alginate. 32625482 8 12 with study 1214:1218 arg1 PGX 1225:1227 PGX 1225:1227 PGX 1225:1227 Considering the no observed adverse effect level of 1.8 g/kg body weight (bw) per day in a subchronic toxicity study with PGX and the highest mean and 95th percentile anticipated daily intake of NF from fortified foods, the margin of exposure (MoE) is 12 and 6, respectively, whereas the MoE for the NF from food supplements is 9. 32625482 8 13 from foods 1316:1320 arg1 intake 1288:1293 daily intake 1282:1293 daily intake of NF from fortified foods 1282:1320 Considering the no observed adverse effect level of 1.8 g/kg body weight (bw) per day in a subchronic toxicity study with PGX and the highest mean and 95th percentile anticipated daily intake of NF from fortified foods, the margin of exposure (MoE) is 12 and 6, respectively, whereas the MoE for the NF from food supplements is 9. 32625482 3 14 theme NF 662:663 arg1 variability 625:635 the batch-to-batch variability 606:635 the batch-to-batch variability 606:635 The information provided on the composition, the specifications, the batch-to-batch variability and the stability of the NF is sufficient and does not raise safety concerns. 32625482 3 14 theme NF 662:663 arg1 stability 645:653 the stability 641:653 the stability of the NF 641:663 The information provided on the composition, the specifications, the batch-to-batch variability and the stability of the NF is sufficient and does not raise safety concerns. 32625482 3 14 theme NF 662:663 arg1 specifications 590:603 the specifications 586:603 the specifications 586:603 The information provided on the composition, the specifications, the batch-to-batch variability and the stability of the NF is sufficient and does not raise safety concerns. 32625482 1 15 theme EC 388:389 arg1 No 258/97 392:400 Regulation (EC) No 258/97 376:400 Regulation (EC) No 258/97 376:400 Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver a scientific opinion on alginate-konjac-xanthan polysaccharide complex (PGX) as a novel food (NF) submitted pursuant to Regulation (EC) No 258/97. 32625482 5 16 theme foods 872:876 arg1 foods 872:876 foods 872:876 foods 872:876 The applicant intends to add the NF to a variety of foods as well as to market the NF in capsules. 32625482 5 16 theme foods 872:876 arg1 variety 861:867 a variety 859:867 a variety of foods 859:876 The applicant intends to add the NF to a variety of foods as well as to market the NF in capsules. 32625482 8 17 from mean 1245:1248 arg1 study 1214:1218 a subchronic toxicity study 1192:1218 a subchronic toxicity study with PGX 1192:1227 Considering the no observed adverse effect level of 1.8 g/kg body weight (bw) per day in a subchronic toxicity study with PGX and the highest mean and 95th percentile anticipated daily intake of NF from fortified foods, the margin of exposure (MoE) is 12 and 6, respectively, whereas the MoE for the NF from food supplements is 9. 32625482 8 18 theme body 1164:1167 arg1 bw 1177:1178 bw 1177:1178 bw 1177:1178 Considering the no observed adverse effect level of 1.8 g/kg body weight (bw) per day in a subchronic toxicity study with PGX and the highest mean and 95th percentile anticipated daily intake of NF from fortified foods, the margin of exposure (MoE) is 12 and 6, respectively, whereas the MoE for the NF from food supplements is 9. 32625482 8 18 theme body 1164:1167 arg1 weight 1169:1174 1.8 g/kg body weight 1155:1174 1.8 g/kg body weight (bw) per day in a subchronic toxicity study with PGX 1155:1227 Considering the no observed adverse effect level of 1.8 g/kg body weight (bw) per day in a subchronic toxicity study with PGX and the highest mean and 95th percentile anticipated daily intake of NF from fortified foods, the margin of exposure (MoE) is 12 and 6, respectively, whereas the MoE for the NF from food supplements is 9. 32625482 3 19 dep safety 698:703 arg1 concerns 705:712 concerns 705:712 concerns 705:712 The information provided on the composition, the specifications, the batch-to-batch variability and the stability of the NF is sufficient and does not raise safety concerns. 32625482 8 20 from supplements 1416:1426 arg1 NF 1403:1404 the NF 1399:1404 the NF from food supplements 1399:1426 Considering the no observed adverse effect level of 1.8 g/kg body weight (bw) per day in a subchronic toxicity study with PGX and the highest mean and 95th percentile anticipated daily intake of NF from fortified foods, the margin of exposure (MoE) is 12 and 6, respectively, whereas the MoE for the NF from food supplements is 9. 32625482 8 21 theme observed 1122:1129 arg1 level 1146:1150 observed adverse effect level 1122:1150 observed adverse effect level of 1.8 g/kg body weight (bw) per day in a subchronic toxicity study with PGX and the highest mean 1122:1248 Considering the no observed adverse effect level of 1.8 g/kg body weight (bw) per day in a subchronic toxicity study with PGX and the highest mean and 95th percentile anticipated daily intake of NF from fortified foods, the margin of exposure (MoE) is 12 and 6, respectively, whereas the MoE for the NF from food supplements is 9. 32625482 8 22 theme subchronic 1194:1203 arg1 study 1214:1218 a subchronic toxicity study 1192:1218 a subchronic toxicity study with PGX 1192:1227 Considering the no observed adverse effect level of 1.8 g/kg body weight (bw) per day in a subchronic toxicity study with PGX and the highest mean and 95th percentile anticipated daily intake of NF from fortified foods, the margin of exposure (MoE) is 12 and 6, respectively, whereas the MoE for the NF from food supplements is 9. 32625482 6 23 theme NF 963:964 arg1 intake 949:954 The recommended maximum daily intake 919:954 The recommended maximum daily intake of the NF from fortified foods and food supplements 919:1006 The recommended maximum daily intake of the NF from fortified foods and food supplements is 15 g. 32625482 6 23 theme NF 963:964 arg1 15 g 1011:1014 15 g 1011:1014 15 g 1011:1014 The recommended maximum daily intake of the NF from fortified foods and food supplements is 15 g. 32625482 0 24 theme Regulation 91:100 arg1 No 258/97 107:115 Regulation (EC) No 258/97 91:115 Regulation (EC) No 258/97 91:115 Safety of alginate-konjac-xanthan polysaccharide complex (PGX) as a novel food pursuant to Regulation (EC) No 258/97. 32625482 8 25 dep no 1119:1120 arg1 anticipated 1270:1280 anticipated 1270:1280 anticipated daily intake of NF from fortified foods 1270:1320 Considering the no observed adverse effect level of 1.8 g/kg body weight (bw) per day in a subchronic toxicity study with PGX and the highest mean and 95th percentile anticipated daily intake of NF from fortified foods, the margin of exposure (MoE) is 12 and 6, respectively, whereas the MoE for the NF from food supplements is 9. 32625482 4 26 theme NF 816:817 arg1 safety 802:807 the safety 798:807 the safety of the NF 798:817 The production process is sufficiently described and does not raise concerns about the safety of the NF. 32625482 1 27 theme Commission 156:165 arg1 Products 195:202 the European Commission, the EFSA Panel on Dietetic Products 143:202 the European Commission, the EFSA Panel on Dietetic Products 143:202 Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver a scientific opinion on alginate-konjac-xanthan polysaccharide complex (PGX) as a novel food (NF) submitted pursuant to Regulation (EC) No 258/97. 32625482 8 28 theme toxicity 1205:1212 arg1 study 1214:1218 a subchronic toxicity study 1192:1218 a subchronic toxicity study with PGX 1192:1227 Considering the no observed adverse effect level of 1.8 g/kg body weight (bw) per day in a subchronic toxicity study with PGX and the highest mean and 95th percentile anticipated daily intake of NF from fortified foods, the margin of exposure (MoE) is 12 and 6, respectively, whereas the MoE for the NF from food supplements is 9. 32625482 0 29 theme polysaccharide 34:47 arg1 PGX 58:60 PGX 58:60 PGX 58:60 Safety of alginate-konjac-xanthan polysaccharide complex (PGX) as a novel food pursuant to Regulation (EC) No 258/97. 32625482 0 29 theme polysaccharide 34:47 arg1 complex 49:55 alginate-konjac-xanthan polysaccharide complex 10:55 alginate-konjac-xanthan polysaccharide complex (PGX) 10:61 Safety of alginate-konjac-xanthan polysaccharide complex (PGX) as a novel food pursuant to Regulation (EC) No 258/97. 32625482 2 30 theme konjac 488:493 arg1 polysaccharides 471:485 three non-starch polysaccharides 454:485 three non-starch polysaccharides: konjac glucomannan, xanthan gum and sodium alginate 454:538 The NF is an off-white granular powder composed of three non-starch polysaccharides: konjac glucomannan, xanthan gum and sodium alginate. 32625482 2 30 theme konjac 488:493 arg1 glucomannan 495:505 konjac glucomannan 488:505 konjac glucomannan 488:505 The NF is an off-white granular powder composed of three non-starch polysaccharides: konjac glucomannan, xanthan gum and sodium alginate. 32625482 8 31 from percentile 1259:1268 arg1 study 1214:1218 a subchronic toxicity study 1192:1218 a subchronic toxicity study with PGX 1192:1227 Considering the no observed adverse effect level of 1.8 g/kg body weight (bw) per day in a subchronic toxicity study with PGX and the highest mean and 95th percentile anticipated daily intake of NF from fortified foods, the margin of exposure (MoE) is 12 and 6, respectively, whereas the MoE for the NF from food supplements is 9. 32625482 6 32 theme daily 943:947 arg1 intake 949:954 The recommended maximum daily intake 919:954 The recommended maximum daily intake of the NF from fortified foods and food supplements 919:1006 The recommended maximum daily intake of the NF from fortified foods and food supplements is 15 g. 32625482 6 32 theme daily 943:947 arg1 15 g 1011:1014 15 g 1011:1014 15 g 1011:1014 The recommended maximum daily intake of the NF from fortified foods and food supplements is 15 g. 32625482 0 33 theme alginate-konjac-xanthan 10:32 arg1 PGX 58:60 PGX 58:60 PGX 58:60 Safety of alginate-konjac-xanthan polysaccharide complex (PGX) as a novel food pursuant to Regulation (EC) No 258/97. 32625482 0 33 theme alginate-konjac-xanthan 10:32 arg1 complex 49:55 alginate-konjac-xanthan polysaccharide complex 10:55 alginate-konjac-xanthan polysaccharide complex (PGX) 10:61 Safety of alginate-konjac-xanthan polysaccharide complex (PGX) as a novel food pursuant to Regulation (EC) No 258/97. 32625482 0 34 theme EC 103:104 arg1 No 258/97 107:115 Regulation (EC) No 258/97 91:115 Regulation (EC) No 258/97 91:115 Safety of alginate-konjac-xanthan polysaccharide complex (PGX) as a novel food pursuant to Regulation (EC) No 258/97. 32625482 1 35 theme novel 338:342 arg1 NF 350:351 NF 350:351 NF 350:351 Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver a scientific opinion on alginate-konjac-xanthan polysaccharide complex (PGX) as a novel food (NF) submitted pursuant to Regulation (EC) No 258/97. 32625482 1 35 theme novel 338:342 arg1 opinion 269:275 a scientific opinion 256:275 a scientific opinion on alginate-konjac-xanthan polysaccharide complex (PGX) 256:331 Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver a scientific opinion on alginate-konjac-xanthan polysaccharide complex (PGX) as a novel food (NF) submitted pursuant to Regulation (EC) No 258/97. 32625482 1 35 theme novel 338:342 arg1 food 344:347 a novel food 336:347 a novel food (NF) submitted pursuant to Regulation (EC) No 258/97 336:400 Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver a scientific opinion on alginate-konjac-xanthan polysaccharide complex (PGX) as a novel food (NF) submitted pursuant to Regulation (EC) No 258/97. 32625482 5 36 from NF 903:904 arg1 capsules 909:916 capsules 909:916 capsules 909:916 The applicant intends to add the NF to a variety of foods as well as to market the NF in capsules. 32625482 6 37 theme maximum 935:941 arg1 intake 949:954 The recommended maximum daily intake 919:954 The recommended maximum daily intake of the NF from fortified foods and food supplements 919:1006 The recommended maximum daily intake of the NF from fortified foods and food supplements is 15 g. 32625482 6 37 theme maximum 935:941 arg1 15 g 1011:1014 15 g 1011:1014 15 g 1011:1014 The recommended maximum daily intake of the NF from fortified foods and food supplements is 15 g. 32625482 7 38 theme target 1021:1026 arg1 population 1028:1037 The target population 1017:1037 The target population proposed by the applicant 1017:1063 The target population proposed by the applicant is adults from 18 to 64 years of age. 32625482 7 38 theme target 1021:1026 arg1 adults 1068:1073 adults 1068:1073 adults from 18 to 64 years of age 1068:1100 The target population proposed by the applicant is adults from 18 to 64 years of age. 32625482 9 39 dep intended 1502:1509 arg1 proposed 1534:1541 proposed 1534:1541 proposed by the applicant 1534:1558 The Panel concludes that the safety of the novel food, PGX, for the intended uses and use levels as proposed by the applicant, has not been established. 32625482 9 39 dep intended 1502:1509 arg1 uses 1511:1514 uses 1511:1514 uses 1511:1514 The Panel concludes that the safety of the novel food, PGX, for the intended uses and use levels as proposed by the applicant, has not been established. 32625482 9 39 dep intended 1502:1509 arg1 levels 1524:1529 levels 1524:1529 levels 1524:1529 The Panel concludes that the safety of the novel food, PGX, for the intended uses and use levels as proposed by the applicant, has not been established. 32625482 8 40 theme daily 1282:1286 arg1 intake 1288:1293 daily intake 1282:1293 daily intake of NF from fortified foods 1282:1320 Considering the no observed adverse effect level of 1.8 g/kg body weight (bw) per day in a subchronic toxicity study with PGX and the highest mean and 95th percentile anticipated daily intake of NF from fortified foods, the margin of exposure (MoE) is 12 and 6, respectively, whereas the MoE for the NF from food supplements is 9. 32625482 6 41 theme recommended 923:933 arg1 intake 949:954 The recommended maximum daily intake 919:954 The recommended maximum daily intake of the NF from fortified foods and food supplements 919:1006 The recommended maximum daily intake of the NF from fortified foods and food supplements is 15 g. 32625482 6 41 theme recommended 923:933 arg1 15 g 1011:1014 15 g 1011:1014 15 g 1011:1014 The recommended maximum daily intake of the NF from fortified foods and food supplements is 15 g. 32625482 0 42 theme complex 49:55 arg1 Safety 0:5 Safety 0:5 Safety of alginate-konjac-xanthan polysaccharide complex (PGX) as a novel food pursuant to Regulation (EC) No 258/97. 0:116 Safety of alginate-konjac-xanthan polysaccharide complex (PGX) as a novel food pursuant to Regulation (EC) No 258/97. 32625482 2 43 theme non-starch 460:469 arg1 alginate 531:538 sodium alginate 524:538 sodium alginate 524:538 The NF is an off-white granular powder composed of three non-starch polysaccharides: konjac glucomannan, xanthan gum and sodium alginate. 32625482 2 43 theme non-starch 460:469 arg1 polysaccharides 471:485 three non-starch polysaccharides 454:485 three non-starch polysaccharides: konjac glucomannan, xanthan gum and sodium alginate 454:538 The NF is an off-white granular powder composed of three non-starch polysaccharides: konjac glucomannan, xanthan gum and sodium alginate. 32625482 2 43 theme non-starch 460:469 arg1 glucomannan 495:505 konjac glucomannan 488:505 konjac glucomannan 488:505 The NF is an off-white granular powder composed of three non-starch polysaccharides: konjac glucomannan, xanthan gum and sodium alginate. 32625482 2 43 theme non-starch 460:469 arg1 gum 516:518 xanthan gum 508:518 xanthan gum 508:518 The NF is an off-white granular powder composed of three non-starch polysaccharides: konjac glucomannan, xanthan gum and sodium alginate. 32625482 8 44 theme NF 1298:1299 arg1 intake 1288:1293 daily intake 1282:1293 daily intake of NF from fortified foods 1282:1320 Considering the no observed adverse effect level of 1.8 g/kg body weight (bw) per day in a subchronic toxicity study with PGX and the highest mean and 95th percentile anticipated daily intake of NF from fortified foods, the margin of exposure (MoE) is 12 and 6, respectively, whereas the MoE for the NF from food supplements is 9. 32625482 6 45 from supplements 996:1006 arg1 intake 949:954 The recommended maximum daily intake 919:954 The recommended maximum daily intake of the NF from fortified foods and food supplements 919:1006 The recommended maximum daily intake of the NF from fortified foods and food supplements is 15 g. 32625482 6 45 from supplements 996:1006 arg1 15 g 1011:1014 15 g 1011:1014 15 g 1011:1014 The recommended maximum daily intake of the NF from fortified foods and food supplements is 15 g. 32625482 8 46 theme effect 1139:1144 arg1 level 1146:1150 observed adverse effect level 1122:1150 observed adverse effect level of 1.8 g/kg body weight (bw) per day in a subchronic toxicity study with PGX and the highest mean 1122:1248 Considering the no observed adverse effect level of 1.8 g/kg body weight (bw) per day in a subchronic toxicity study with PGX and the highest mean and 95th percentile anticipated daily intake of NF from fortified foods, the margin of exposure (MoE) is 12 and 6, respectively, whereas the MoE for the NF from food supplements is 9. 32625482 1 47 theme scientific 258:267 arg1 opinion 269:275 a scientific opinion 256:275 a scientific opinion on alginate-konjac-xanthan polysaccharide complex (PGX) 256:331 Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver a scientific opinion on alginate-konjac-xanthan polysaccharide complex (PGX) as a novel food (NF) submitted pursuant to Regulation (EC) No 258/97. 32625482 1 47 theme scientific 258:267 arg1 food 344:347 a novel food 336:347 a novel food (NF) submitted pursuant to Regulation (EC) No 258/97 336:400 Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver a scientific opinion on alginate-konjac-xanthan polysaccharide complex (PGX) as a novel food (NF) submitted pursuant to Regulation (EC) No 258/97. 32625482 9 48 theme PGX 1489:1491 arg1 safety 1463:1468 the safety 1459:1468 the safety of the novel food, PGX 1459:1491 The Panel concludes that the safety of the novel food, PGX, for the intended uses and use levels as proposed by the applicant, has not been established. 32625482 7 49 theme age 1098:1100 arg1 64 years 1086:1093 64 years 1086:1093 64 years of age 1086:1100 The target population proposed by the applicant is adults from 18 to 64 years of age. 32625482 8 50 theme mean 1245:1248 arg1 percentile 1259:1268 95th percentile 1254:1268 95th percentile 1254:1268 Considering the no observed adverse effect level of 1.8 g/kg body weight (bw) per day in a subchronic toxicity study with PGX and the highest mean and 95th percentile anticipated daily intake of NF from fortified foods, the margin of exposure (MoE) is 12 and 6, respectively, whereas the MoE for the NF from food supplements is 9. 32625482 8 50 theme mean 1245:1248 arg1 level 1146:1150 observed adverse effect level 1122:1150 observed adverse effect level of 1.8 g/kg body weight (bw) per day in a subchronic toxicity study with PGX and the highest mean 1122:1248 Considering the no observed adverse effect level of 1.8 g/kg body weight (bw) per day in a subchronic toxicity study with PGX and the highest mean and 95th percentile anticipated daily intake of NF from fortified foods, the margin of exposure (MoE) is 12 and 6, respectively, whereas the MoE for the NF from food supplements is 9. 32625482 8 51 theme 1.8 g/kg 1155:1162 arg1 bw 1177:1178 bw 1177:1178 bw 1177:1178 Considering the no observed adverse effect level of 1.8 g/kg body weight (bw) per day in a subchronic toxicity study with PGX and the highest mean and 95th percentile anticipated daily intake of NF from fortified foods, the margin of exposure (MoE) is 12 and 6, respectively, whereas the MoE for the NF from food supplements is 9. 32625482 8 51 theme 1.8 g/kg 1155:1162 arg1 weight 1169:1174 1.8 g/kg body weight 1155:1174 1.8 g/kg body weight (bw) per day in a subchronic toxicity study with PGX 1155:1227 Considering the no observed adverse effect level of 1.8 g/kg body weight (bw) per day in a subchronic toxicity study with PGX and the highest mean and 95th percentile anticipated daily intake of NF from fortified foods, the margin of exposure (MoE) is 12 and 6, respectively, whereas the MoE for the NF from food supplements is 9. 32625482 2 52 theme xanthan 508:514 arg1 polysaccharides 471:485 three non-starch polysaccharides 454:485 three non-starch polysaccharides: konjac glucomannan, xanthan gum and sodium alginate 454:538 The NF is an off-white granular powder composed of three non-starch polysaccharides: konjac glucomannan, xanthan gum and sodium alginate. 32625482 2 52 theme xanthan 508:514 arg1 gum 516:518 xanthan gum 508:518 xanthan gum 508:518 The NF is an off-white granular powder composed of three non-starch polysaccharides: konjac glucomannan, xanthan gum and sodium alginate. 32625482 8 53 theme fortified 1306:1314 arg1 foods 1316:1320 fortified foods 1306:1320 fortified foods 1306:1320 Considering the no observed adverse effect level of 1.8 g/kg body weight (bw) per day in a subchronic toxicity study with PGX and the highest mean and 95th percentile anticipated daily intake of NF from fortified foods, the margin of exposure (MoE) is 12 and 6, respectively, whereas the MoE for the NF from food supplements is 9. 32625482 8 54 theme highest 1237:1243 arg1 mean 1245:1248 the highest mean 1233:1248 the highest mean 1233:1248 Considering the no observed adverse effect level of 1.8 g/kg body weight (bw) per day in a subchronic toxicity study with PGX and the highest mean and 95th percentile anticipated daily intake of NF from fortified foods, the margin of exposure (MoE) is 12 and 6, respectively, whereas the MoE for the NF from food supplements is 9. 32625482 1 55 from Products 195:202 arg1 request 130:136 a request 128:136 a request from the European Commission, the EFSA Panel on Dietetic Products 128:202 Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver a scientific opinion on alginate-konjac-xanthan polysaccharide complex (PGX) as a novel food (NF) submitted pursuant to Regulation (EC) No 258/97. 32625482 3 56 theme batch-to-batch 610:623 arg1 variability 625:635 the batch-to-batch variability 606:635 the batch-to-batch variability 606:635 The information provided on the composition, the specifications, the batch-to-batch variability and the stability of the NF is sufficient and does not raise safety concerns. 32625482 3 56 theme batch-to-batch 610:623 arg1 specifications 590:603 the specifications 586:603 the specifications 586:603 The information provided on the composition, the specifications, the batch-to-batch variability and the stability of the NF is sufficient and does not raise safety concerns. 32625482 4 57 theme production 719:728 arg1 process 730:736 The production process 715:736 The production process 715:736 The production process is sufficiently described and does not raise concerns about the safety of the NF. 32625482 8 58 theme weight 1169:1174 arg1 percentile 1259:1268 95th percentile 1254:1268 95th percentile 1254:1268 Considering the no observed adverse effect level of 1.8 g/kg body weight (bw) per day in a subchronic toxicity study with PGX and the highest mean and 95th percentile anticipated daily intake of NF from fortified foods, the margin of exposure (MoE) is 12 and 6, respectively, whereas the MoE for the NF from food supplements is 9. 32625482 8 58 theme weight 1169:1174 arg1 level 1146:1150 observed adverse effect level 1122:1150 observed adverse effect level of 1.8 g/kg body weight (bw) per day in a subchronic toxicity study with PGX and the highest mean 1122:1248 Considering the no observed adverse effect level of 1.8 g/kg body weight (bw) per day in a subchronic toxicity study with PGX and the highest mean and 95th percentile anticipated daily intake of NF from fortified foods, the margin of exposure (MoE) is 12 and 6, respectively, whereas the MoE for the NF from food supplements is 9. 32625482 8 59 from level 1146:1150 arg1 study 1214:1218 a subchronic toxicity study 1192:1218 a subchronic toxicity study with PGX 1192:1227 Considering the no observed adverse effect level of 1.8 g/kg body weight (bw) per day in a subchronic toxicity study with PGX and the highest mean and 95th percentile anticipated daily intake of NF from fortified foods, the margin of exposure (MoE) is 12 and 6, respectively, whereas the MoE for the NF from food supplements is 9. 32625482 6 60 theme food 991:994 arg1 supplements 996:1006 food supplements 991:1006 food supplements 991:1006 The recommended maximum daily intake of the NF from fortified foods and food supplements is 15 g. 32625482 8 61 from weight 1169:1174 arg1 study 1214:1218 a subchronic toxicity study 1192:1218 a subchronic toxicity study with PGX 1192:1227 Considering the no observed adverse effect level of 1.8 g/kg body weight (bw) per day in a subchronic toxicity study with PGX and the highest mean and 95th percentile anticipated daily intake of NF from fortified foods, the margin of exposure (MoE) is 12 and 6, respectively, whereas the MoE for the NF from food supplements is 9. 32625482 2 62 theme granular 426:433 arg1 powder 435:440 an off-white granular powder 413:440 an off-white granular powder composed of three non-starch polysaccharides: konjac glucomannan, xanthan gum and sodium alginate 413:538 The NF is an off-white granular powder composed of three non-starch polysaccharides: konjac glucomannan, xanthan gum and sodium alginate. 32625482 2 62 theme granular 426:433 arg1 NF 407:408 The NF 403:408 The NF 403:408 The NF is an off-white granular powder composed of three non-starch polysaccharides: konjac glucomannan, xanthan gum and sodium alginate. 32625482 8 63 dep 12 1355:1356 arg1 whereas 1379:1385 whereas 1379:1385 whereas 1379:1385 Considering the no observed adverse effect level of 1.8 g/kg body weight (bw) per day in a subchronic toxicity study with PGX and the highest mean and 95th percentile anticipated daily intake of NF from fortified foods, the margin of exposure (MoE) is 12 and 6, respectively, whereas the MoE for the NF from food supplements is 9. 32625482 8 64 theme adverse 1131:1137 arg1 level 1146:1150 observed adverse effect level 1122:1150 observed adverse effect level of 1.8 g/kg body weight (bw) per day in a subchronic toxicity study with PGX and the highest mean 1122:1248 Considering the no observed adverse effect level of 1.8 g/kg body weight (bw) per day in a subchronic toxicity study with PGX and the highest mean and 95th percentile anticipated daily intake of NF from fortified foods, the margin of exposure (MoE) is 12 and 6, respectively, whereas the MoE for the NF from food supplements is 9. 32625482 2 65 theme off-white 416:424 arg1 powder 435:440 an off-white granular powder 413:440 an off-white granular powder composed of three non-starch polysaccharides: konjac glucomannan, xanthan gum and sodium alginate 413:538 The NF is an off-white granular powder composed of three non-starch polysaccharides: konjac glucomannan, xanthan gum and sodium alginate. 32625482 2 65 theme off-white 416:424 arg1 NF 407:408 The NF 403:408 The NF 403:408 The NF is an off-white granular powder composed of three non-starch polysaccharides: konjac glucomannan, xanthan gum and sodium alginate. 32625482 1 66 theme alginate-konjac-xanthan 280:302 arg1 complex 319:325 alginate-konjac-xanthan polysaccharide complex 280:325 alginate-konjac-xanthan polysaccharide complex (PGX) 280:331 Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver a scientific opinion on alginate-konjac-xanthan polysaccharide complex (PGX) as a novel food (NF) submitted pursuant to Regulation (EC) No 258/97. 32625482 1 66 theme alginate-konjac-xanthan 280:302 arg1 PGX 328:330 PGX 328:330 PGX 328:330 Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver a scientific opinion on alginate-konjac-xanthan polysaccharide complex (PGX) as a novel food (NF) submitted pursuant to Regulation (EC) No 258/97. 28439294 0 0 theme poplar 73:78 arg1 pretreatment 57:68 ionic liquid pretreatment 44:68 ionic liquid pretreatment of poplar 44:78 Impact of lignin polymer backbone esters on ionic liquid pretreatment of poplar. 28439294 6 1 theme lignin 1373:1378 arg1 backbone 1388:1395 the lignin polymer backbone 1369:1395 the lignin polymer backbone 1369:1395 CONCLUSION Our findings clearly demonstrate that the introduction of ester linkages into the lignin polymer backbone decreases biomass recalcitrance in poplar has the potential to reduce the energy and/or amount of IL required for effective pretreatment, and could enable the development of an economically viable and sustainable biorefinery process. 28439294 1 2 theme biofuel 158:164 arg1 production 166:175 lignocellulosic biofuel production 142:175 lignocellulosic biofuel production 142:175 BACKGROUND Biomass pretreatment remains an essential step in lignocellulosic biofuel production, largely to facilitate the efficient removal of lignin and increase enzyme accessibility to the polysaccharides. 28439294 3 3 dep wild-type 756:764 arg1 WT 767:768 WT 767:768 WT 767:768 Here, transgenic poplar lines in which monolignol ferulate conjugates were synthesized during cell wall development to introduce, during lignification, readily cleavable ester linkages into the lignin polymer backbone (i.e., "zip lignin"), along with wild-type (WT) controls, were pretreated with different ionic liquids (ILs). 28439294 3 4 theme ionic 812:816 arg1 ILs 827:829 ILs 827:829 ILs 827:829 Here, transgenic poplar lines in which monolignol ferulate conjugates were synthesized during cell wall development to introduce, during lignification, readily cleavable ester linkages into the lignin polymer backbone (i.e., "zip lignin"), along with wild-type (WT) controls, were pretreated with different ionic liquids (ILs). 28439294 3 4 theme ionic 812:816 arg1 liquids 818:824 different ionic liquids 802:824 different ionic liquids (ILs) 802:830 Here, transgenic poplar lines in which monolignol ferulate conjugates were synthesized during cell wall development to introduce, during lignification, readily cleavable ester linkages into the lignin polymer backbone (i.e., "zip lignin"), along with wild-type (WT) controls, were pretreated with different ionic liquids (ILs). 28439294 6 5 theme polymer 1380:1386 arg1 backbone 1388:1395 the lignin polymer backbone 1369:1395 the lignin polymer backbone 1369:1395 CONCLUSION Our findings clearly demonstrate that the introduction of ester linkages into the lignin polymer backbone decreases biomass recalcitrance in poplar has the potential to reduce the energy and/or amount of IL required for effective pretreatment, and could enable the development of an economically viable and sustainable biorefinery process. 28439294 2 6 from efforts 335:341 arg1 years 300:304 recent years 293:304 recent years 293:304 In recent years, there have been significant efforts in planta to reduce lignin content or modify its composition to overcome the inherent recalcitrance that it imposes on lignocellulosic biomass during processing. 28439294 2 6 from efforts 335:341 arg1 planta 346:351 planta 346:351 planta 346:351 In recent years, there have been significant efforts in planta to reduce lignin content or modify its composition to overcome the inherent recalcitrance that it imposes on lignocellulosic biomass during processing. 28439294 3 7 theme poplar 522:527 arg1 lines 529:533 transgenic poplar lines 511:533 transgenic poplar lines 511:533 Here, transgenic poplar lines in which monolignol ferulate conjugates were synthesized during cell wall development to introduce, during lignification, readily cleavable ester linkages into the lignin polymer backbone (i.e., "zip lignin"), along with wild-type (WT) controls, were pretreated with different ionic liquids (ILs). 28439294 5 8 theme conjugates 1207:1216 arg1 conjugates 1207:1216 incorporated monolignol ferulate conjugates 1174:1216 incorporated monolignol ferulate conjugates 1174:1216 After pretreatment with any of three different ILs, and after limited saccharification, the transgenic poplars, especially those with relatively higher amounts of incorporated monolignol ferulate conjugates, yielded up to 23% higher sugar levels compared to WT plants. 28439294 5 8 theme conjugates 1207:1216 arg1 amounts 1163:1169 relatively higher amounts 1145:1169 relatively higher amounts of incorporated monolignol ferulate conjugates 1145:1216 After pretreatment with any of three different ILs, and after limited saccharification, the transgenic poplars, especially those with relatively higher amounts of incorporated monolignol ferulate conjugates, yielded up to 23% higher sugar levels compared to WT plants. 28439294 4 9 theme increased 920:928 arg1 efficiency 943:952 increased pretreatment efficiency 920:952 increased pretreatment efficiency 920:952 RESULTS The strategic introduction of ester bonds into the lignin backbone resulted in increased pretreatment efficiency and released more carbohydrates with lower energy input. 28439294 0 10 from Impact 0:5 arg1 pretreatment 57:68 ionic liquid pretreatment 44:68 ionic liquid pretreatment of poplar 44:78 Impact of lignin polymer backbone esters on ionic liquid pretreatment of poplar. 28439294 6 11 theme biomass 1407:1413 arg1 recalcitrance 1415:1427 biomass recalcitrance 1407:1427 biomass recalcitrance in poplar has the potential to reduce the energy and/or amount of IL required for effective pretreatment, and could enable the development of an economically viable and sustainable biorefinery process 1407:1628 CONCLUSION Our findings clearly demonstrate that the introduction of ester linkages into the lignin polymer backbone decreases biomass recalcitrance in poplar has the potential to reduce the energy and/or amount of IL required for effective pretreatment, and could enable the development of an economically viable and sustainable biorefinery process. 28439294 3 12 theme ferulate 555:562 arg1 conjugates 564:573 monolignol ferulate conjugates 544:573 monolignol ferulate conjugates 544:573 Here, transgenic poplar lines in which monolignol ferulate conjugates were synthesized during cell wall development to introduce, during lignification, readily cleavable ester linkages into the lignin polymer backbone (i.e., "zip lignin"), along with wild-type (WT) controls, were pretreated with different ionic liquids (ILs). 28439294 6 13 theme linkages 1355:1362 arg1 introduction 1333:1344 the introduction 1329:1344 the introduction of ester linkages into the lignin polymer backbone 1329:1395 CONCLUSION Our findings clearly demonstrate that the introduction of ester linkages into the lignin polymer backbone decreases biomass recalcitrance in poplar has the potential to reduce the energy and/or amount of IL required for effective pretreatment, and could enable the development of an economically viable and sustainable biorefinery process. 28439294 3 14 theme lignin 735:740 arg1 backbone 714:721 the lignin polymer backbone 695:721 the lignin polymer backbone (i.e., "zip lignin") 695:742 Here, transgenic poplar lines in which monolignol ferulate conjugates were synthesized during cell wall development to introduce, during lignification, readily cleavable ester linkages into the lignin polymer backbone (i.e., "zip lignin"), along with wild-type (WT) controls, were pretreated with different ionic liquids (ILs). 28439294 3 14 theme lignin 735:740 arg1 " 741:741 "zip lignin" 730:741 "zip lignin" 730:741 Here, transgenic poplar lines in which monolignol ferulate conjugates were synthesized during cell wall development to introduce, during lignification, readily cleavable ester linkages into the lignin polymer backbone (i.e., "zip lignin"), along with wild-type (WT) controls, were pretreated with different ionic liquids (ILs). 28439294 4 15 theme strategic 845:853 arg1 introduction 855:866 The strategic introduction 841:866 The strategic introduction of ester bonds into the lignin backbone 841:906 RESULTS The strategic introduction of ester bonds into the lignin backbone resulted in increased pretreatment efficiency and released more carbohydrates with lower energy input. 28439294 2 16 theme recent 293:298 arg1 years 300:304 recent years 293:304 recent years 293:304 In recent years, there have been significant efforts in planta to reduce lignin content or modify its composition to overcome the inherent recalcitrance that it imposes on lignocellulosic biomass during processing. 28439294 3 17 theme different 802:810 arg1 ILs 827:829 ILs 827:829 ILs 827:829 Here, transgenic poplar lines in which monolignol ferulate conjugates were synthesized during cell wall development to introduce, during lignification, readily cleavable ester linkages into the lignin polymer backbone (i.e., "zip lignin"), along with wild-type (WT) controls, were pretreated with different ionic liquids (ILs). 28439294 3 17 theme different 802:810 arg1 liquids 818:824 different ionic liquids 802:824 different ionic liquids (ILs) 802:830 Here, transgenic poplar lines in which monolignol ferulate conjugates were synthesized during cell wall development to introduce, during lignification, readily cleavable ester linkages into the lignin polymer backbone (i.e., "zip lignin"), along with wild-type (WT) controls, were pretreated with different ionic liquids (ILs). 28439294 6 18 theme ester 1349:1353 arg1 linkages 1355:1362 ester linkages 1349:1362 ester linkages 1349:1362 CONCLUSION Our findings clearly demonstrate that the introduction of ester linkages into the lignin polymer backbone decreases biomass recalcitrance in poplar has the potential to reduce the energy and/or amount of IL required for effective pretreatment, and could enable the development of an economically viable and sustainable biorefinery process. 28439294 5 19 theme sugar 1244:1248 arg1 levels 1250:1255 up to 23% higher sugar levels 1227:1255 up to 23% higher sugar levels 1227:1255 After pretreatment with any of three different ILs, and after limited saccharification, the transgenic poplars, especially those with relatively higher amounts of incorporated monolignol ferulate conjugates, yielded up to 23% higher sugar levels compared to WT plants. 28439294 4 20 theme pretreatment 930:941 arg1 efficiency 943:952 increased pretreatment efficiency 920:952 increased pretreatment efficiency 920:952 RESULTS The strategic introduction of ester bonds into the lignin backbone resulted in increased pretreatment efficiency and released more carbohydrates with lower energy input. 28439294 4 21 theme lower 991:995 arg1 input 1004:1008 lower energy input 991:1008 lower energy input 991:1008 RESULTS The strategic introduction of ester bonds into the lignin backbone resulted in increased pretreatment efficiency and released more carbohydrates with lower energy input. 28439294 3 22 theme monolignol 544:553 arg1 conjugates 564:573 monolignol ferulate conjugates 544:573 monolignol ferulate conjugates 544:573 Here, transgenic poplar lines in which monolignol ferulate conjugates were synthesized during cell wall development to introduce, during lignification, readily cleavable ester linkages into the lignin polymer backbone (i.e., "zip lignin"), along with wild-type (WT) controls, were pretreated with different ionic liquids (ILs). 28439294 3 23 theme zip 731:733 arg1 backbone 714:721 the lignin polymer backbone 695:721 the lignin polymer backbone (i.e., "zip lignin") 695:742 Here, transgenic poplar lines in which monolignol ferulate conjugates were synthesized during cell wall development to introduce, during lignification, readily cleavable ester linkages into the lignin polymer backbone (i.e., "zip lignin"), along with wild-type (WT) controls, were pretreated with different ionic liquids (ILs). 28439294 3 23 theme zip 731:733 arg1 " 741:741 "zip lignin" 730:741 "zip lignin" 730:741 Here, transgenic poplar lines in which monolignol ferulate conjugates were synthesized during cell wall development to introduce, during lignification, readily cleavable ester linkages into the lignin polymer backbone (i.e., "zip lignin"), along with wild-type (WT) controls, were pretreated with different ionic liquids (ILs). 28439294 1 24 from step 134:137 arg1 production 166:175 lignocellulosic biofuel production 142:175 lignocellulosic biofuel production 142:175 BACKGROUND Biomass pretreatment remains an essential step in lignocellulosic biofuel production, largely to facilitate the efficient removal of lignin and increase enzyme accessibility to the polysaccharides. 28439294 5 25 theme higher 1156:1161 arg1 conjugates 1207:1216 incorporated monolignol ferulate conjugates 1174:1216 incorporated monolignol ferulate conjugates 1174:1216 After pretreatment with any of three different ILs, and after limited saccharification, the transgenic poplars, especially those with relatively higher amounts of incorporated monolignol ferulate conjugates, yielded up to 23% higher sugar levels compared to WT plants. 28439294 5 25 theme higher 1156:1161 arg1 amounts 1163:1169 relatively higher amounts 1145:1169 relatively higher amounts of incorporated monolignol ferulate conjugates 1145:1216 After pretreatment with any of three different ILs, and after limited saccharification, the transgenic poplars, especially those with relatively higher amounts of incorporated monolignol ferulate conjugates, yielded up to 23% higher sugar levels compared to WT plants. 28439294 5 26 theme limited 1073:1079 arg1 saccharification 1081:1096 limited saccharification 1073:1096 limited saccharification 1073:1096 After pretreatment with any of three different ILs, and after limited saccharification, the transgenic poplars, especially those with relatively higher amounts of incorporated monolignol ferulate conjugates, yielded up to 23% higher sugar levels compared to WT plants. 28439294 6 27 dep CONCLUSION 1280:1289 arg1 demonstrate 1312:1322 demonstrate 1312:1322 demonstrate that the introduction of ester linkages into the lignin polymer backbone decreases biomass recalcitrance in poplar has the potential to reduce the energy and/or amount of IL required for effective pretreatment, and could enable the development of an economically viable and sustainable biorefinery process 1312:1628 CONCLUSION Our findings clearly demonstrate that the introduction of ester linkages into the lignin polymer backbone decreases biomass recalcitrance in poplar has the potential to reduce the energy and/or amount of IL required for effective pretreatment, and could enable the development of an economically viable and sustainable biorefinery process. 28439294 5 28 theme ferulate 1198:1205 arg1 conjugates 1207:1216 incorporated monolignol ferulate conjugates 1174:1216 incorporated monolignol ferulate conjugates 1174:1216 After pretreatment with any of three different ILs, and after limited saccharification, the transgenic poplars, especially those with relatively higher amounts of incorporated monolignol ferulate conjugates, yielded up to 23% higher sugar levels compared to WT plants. 28439294 6 29 theme process 1622:1628 arg1 development 1556:1566 the development 1552:1566 the development of an economically viable and sustainable biorefinery process 1552:1628 CONCLUSION Our findings clearly demonstrate that the introduction of ester linkages into the lignin polymer backbone decreases biomass recalcitrance in poplar has the potential to reduce the energy and/or amount of IL required for effective pretreatment, and could enable the development of an economically viable and sustainable biorefinery process. 28439294 1 30 theme BACKGROUND 81:90 arg1 pretreatment 100:111 BACKGROUND Biomass pretreatment 81:111 BACKGROUND Biomass pretreatment 81:111 BACKGROUND Biomass pretreatment remains an essential step in lignocellulosic biofuel production, largely to facilitate the efficient removal of lignin and increase enzyme accessibility to the polysaccharides. 28439294 0 31 theme polymer 17:23 arg1 esters 34:39 lignin polymer backbone esters 10:39 lignin polymer backbone esters 10:39 Impact of lignin polymer backbone esters on ionic liquid pretreatment of poplar. 28439294 4 32 theme lignin 892:897 arg1 backbone 899:906 the lignin backbone 888:906 the lignin backbone 888:906 RESULTS The strategic introduction of ester bonds into the lignin backbone resulted in increased pretreatment efficiency and released more carbohydrates with lower energy input. 28439294 6 33 theme biorefinery 1610:1620 arg1 process 1622:1628 an economically viable and sustainable biorefinery process 1571:1628 an economically viable and sustainable biorefinery process 1571:1628 CONCLUSION Our findings clearly demonstrate that the introduction of ester linkages into the lignin polymer backbone decreases biomass recalcitrance in poplar has the potential to reduce the energy and/or amount of IL required for effective pretreatment, and could enable the development of an economically viable and sustainable biorefinery process. 28439294 1 34 theme Biomass 92:98 arg1 pretreatment 100:111 BACKGROUND Biomass pretreatment 81:111 BACKGROUND Biomass pretreatment 81:111 BACKGROUND Biomass pretreatment remains an essential step in lignocellulosic biofuel production, largely to facilitate the efficient removal of lignin and increase enzyme accessibility to the polysaccharides. 28439294 6 35 theme effective 1511:1519 arg1 pretreatment 1521:1532 effective pretreatment 1511:1532 effective pretreatment 1511:1532 CONCLUSION Our findings clearly demonstrate that the introduction of ester linkages into the lignin polymer backbone decreases biomass recalcitrance in poplar has the potential to reduce the energy and/or amount of IL required for effective pretreatment, and could enable the development of an economically viable and sustainable biorefinery process. 28439294 2 36 theme inherent 420:427 arg1 recalcitrance 429:441 the inherent recalcitrance 416:441 the inherent recalcitrance that it imposes on lignocellulosic biomass during processing 416:502 In recent years, there have been significant efforts in planta to reduce lignin content or modify its composition to overcome the inherent recalcitrance that it imposes on lignocellulosic biomass during processing. 28439294 0 37 theme lignin 10:15 arg1 esters 34:39 lignin polymer backbone esters 10:39 lignin polymer backbone esters 10:39 Impact of lignin polymer backbone esters on ionic liquid pretreatment of poplar. 28439294 5 38 theme incorporated 1174:1185 arg1 conjugates 1207:1216 incorporated monolignol ferulate conjugates 1174:1216 incorporated monolignol ferulate conjugates 1174:1216 After pretreatment with any of three different ILs, and after limited saccharification, the transgenic poplars, especially those with relatively higher amounts of incorporated monolignol ferulate conjugates, yielded up to 23% higher sugar levels compared to WT plants. 28439294 6 39 dep energy 1471:1476 arg1 the 1467:1469 the 1467:1469 the 1467:1469 CONCLUSION Our findings clearly demonstrate that the introduction of ester linkages into the lignin polymer backbone decreases biomass recalcitrance in poplar has the potential to reduce the energy and/or amount of IL required for effective pretreatment, and could enable the development of an economically viable and sustainable biorefinery process. 28439294 3 40 theme ester 675:679 arg1 linkages 681:688 readily cleavable ester linkages 657:688 readily cleavable ester linkages 657:688 Here, transgenic poplar lines in which monolignol ferulate conjugates were synthesized during cell wall development to introduce, during lignification, readily cleavable ester linkages into the lignin polymer backbone (i.e., "zip lignin"), along with wild-type (WT) controls, were pretreated with different ionic liquids (ILs). 28439294 5 41 with pretreatment 1017:1028 arg1 any 1035:1037 any 1035:1037 any 1035:1037 After pretreatment with any of three different ILs, and after limited saccharification, the transgenic poplars, especially those with relatively higher amounts of incorporated monolignol ferulate conjugates, yielded up to 23% higher sugar levels compared to WT plants. 28439294 1 42 theme efficient 204:212 arg1 removal 214:220 the efficient removal 200:220 the efficient removal of lignin 200:230 BACKGROUND Biomass pretreatment remains an essential step in lignocellulosic biofuel production, largely to facilitate the efficient removal of lignin and increase enzyme accessibility to the polysaccharides. 28439294 0 43 theme esters 34:39 arg1 Impact 0:5 Impact 0:5 Impact of lignin polymer backbone esters on ionic liquid pretreatment of poplar. 0:79 Impact of lignin polymer backbone esters on ionic liquid pretreatment of poplar. 28439294 5 44 theme monolignol 1187:1196 arg1 conjugates 1207:1216 incorporated monolignol ferulate conjugates 1174:1216 incorporated monolignol ferulate conjugates 1174:1216 After pretreatment with any of three different ILs, and after limited saccharification, the transgenic poplars, especially those with relatively higher amounts of incorporated monolignol ferulate conjugates, yielded up to 23% higher sugar levels compared to WT plants. 28439294 3 45 theme cell 599:602 arg1 development 609:619 cell wall development 599:619 cell wall development 599:619 Here, transgenic poplar lines in which monolignol ferulate conjugates were synthesized during cell wall development to introduce, during lignification, readily cleavable ester linkages into the lignin polymer backbone (i.e., "zip lignin"), along with wild-type (WT) controls, were pretreated with different ionic liquids (ILs). 28439294 0 46 theme backbone 25:32 arg1 esters 34:39 lignin polymer backbone esters 10:39 lignin polymer backbone esters 10:39 Impact of lignin polymer backbone esters on ionic liquid pretreatment of poplar. 28439294 6 47 dep recalcitrance 1415:1427 arg1 has 1439:1441 has 1439:1441 has the potential to reduce the energy and/or amount of IL required for effective pretreatment 1439:1532 CONCLUSION Our findings clearly demonstrate that the introduction of ester linkages into the lignin polymer backbone decreases biomass recalcitrance in poplar has the potential to reduce the energy and/or amount of IL required for effective pretreatment, and could enable the development of an economically viable and sustainable biorefinery process. 28439294 6 47 dep recalcitrance 1415:1427 arg1 enable 1545:1550 enable 1545:1550 could enable the development of an economically viable and sustainable biorefinery process 1539:1628 CONCLUSION Our findings clearly demonstrate that the introduction of ester linkages into the lignin polymer backbone decreases biomass recalcitrance in poplar has the potential to reduce the energy and/or amount of IL required for effective pretreatment, and could enable the development of an economically viable and sustainable biorefinery process. 28439294 6 48 theme sustainable 1598:1608 arg1 process 1622:1628 an economically viable and sustainable biorefinery process 1571:1628 an economically viable and sustainable biorefinery process 1571:1628 CONCLUSION Our findings clearly demonstrate that the introduction of ester linkages into the lignin polymer backbone decreases biomass recalcitrance in poplar has the potential to reduce the energy and/or amount of IL required for effective pretreatment, and could enable the development of an economically viable and sustainable biorefinery process. 28439294 3 49 theme cleavable 665:673 arg1 linkages 681:688 readily cleavable ester linkages 657:688 readily cleavable ester linkages 657:688 Here, transgenic poplar lines in which monolignol ferulate conjugates were synthesized during cell wall development to introduce, during lignification, readily cleavable ester linkages into the lignin polymer backbone (i.e., "zip lignin"), along with wild-type (WT) controls, were pretreated with different ionic liquids (ILs). 28439294 2 50 theme lignocellulosic 462:476 arg1 biomass 478:484 lignocellulosic biomass 462:484 lignocellulosic biomass during processing 462:502 In recent years, there have been significant efforts in planta to reduce lignin content or modify its composition to overcome the inherent recalcitrance that it imposes on lignocellulosic biomass during processing. 28439294 3 51 theme transgenic 511:520 arg1 lines 529:533 transgenic poplar lines 511:533 transgenic poplar lines 511:533 Here, transgenic poplar lines in which monolignol ferulate conjugates were synthesized during cell wall development to introduce, during lignification, readily cleavable ester linkages into the lignin polymer backbone (i.e., "zip lignin"), along with wild-type (WT) controls, were pretreated with different ionic liquids (ILs). 28439294 4 52 theme ester 871:875 arg1 bonds 877:881 ester bonds 871:881 ester bonds 871:881 RESULTS The strategic introduction of ester bonds into the lignin backbone resulted in increased pretreatment efficiency and released more carbohydrates with lower energy input. 28439294 0 53 theme liquid 50:55 arg1 pretreatment 57:68 ionic liquid pretreatment 44:68 ionic liquid pretreatment of poplar 44:78 Impact of lignin polymer backbone esters on ionic liquid pretreatment of poplar. 28439294 3 54 theme wall 604:607 arg1 development 609:619 cell wall development 599:619 cell wall development 599:619 Here, transgenic poplar lines in which monolignol ferulate conjugates were synthesized during cell wall development to introduce, during lignification, readily cleavable ester linkages into the lignin polymer backbone (i.e., "zip lignin"), along with wild-type (WT) controls, were pretreated with different ionic liquids (ILs). 28439294 6 55 contain has 1439:1441 arg2 potential 1447:1455 the potential to reduce the energy and/or amount of IL required for effective pretreatment 1443:1532 the potential to reduce the energy and/or amount of IL required for effective pretreatment 1443:1532 CONCLUSION Our findings clearly demonstrate that the introduction of ester linkages into the lignin polymer backbone decreases biomass recalcitrance in poplar has the potential to reduce the energy and/or amount of IL required for effective pretreatment, and could enable the development of an economically viable and sustainable biorefinery process. 28439294 6 55 contain has 1439:1441 arg1 poplar 1432:1437 poplar 1432:1437 poplar 1432:1437 CONCLUSION Our findings clearly demonstrate that the introduction of ester linkages into the lignin polymer backbone decreases biomass recalcitrance in poplar has the potential to reduce the energy and/or amount of IL required for effective pretreatment, and could enable the development of an economically viable and sustainable biorefinery process. 28439294 4 56 theme energy 997:1002 arg1 input 1004:1008 lower energy input 991:1008 lower energy input 991:1008 RESULTS The strategic introduction of ester bonds into the lignin backbone resulted in increased pretreatment efficiency and released more carbohydrates with lower energy input. 28439294 3 57 theme wild-type 756:764 arg1 controls 771:778 wild-type (WT) controls 756:778 wild-type (WT) controls 756:778 Here, transgenic poplar lines in which monolignol ferulate conjugates were synthesized during cell wall development to introduce, during lignification, readily cleavable ester linkages into the lignin polymer backbone (i.e., "zip lignin"), along with wild-type (WT) controls, were pretreated with different ionic liquids (ILs). 28439294 3 58 theme lignin 699:704 arg1 backbone 714:721 the lignin polymer backbone 695:721 the lignin polymer backbone (i.e., "zip lignin") 695:742 Here, transgenic poplar lines in which monolignol ferulate conjugates were synthesized during cell wall development to introduce, during lignification, readily cleavable ester linkages into the lignin polymer backbone (i.e., "zip lignin"), along with wild-type (WT) controls, were pretreated with different ionic liquids (ILs). 28439294 3 58 theme lignin 699:704 arg1 " 741:741 "zip lignin" 730:741 "zip lignin" 730:741 Here, transgenic poplar lines in which monolignol ferulate conjugates were synthesized during cell wall development to introduce, during lignification, readily cleavable ester linkages into the lignin polymer backbone (i.e., "zip lignin"), along with wild-type (WT) controls, were pretreated with different ionic liquids (ILs). 28439294 1 59 theme lignocellulosic 142:156 arg1 production 166:175 lignocellulosic biofuel production 142:175 lignocellulosic biofuel production 142:175 BACKGROUND Biomass pretreatment remains an essential step in lignocellulosic biofuel production, largely to facilitate the efficient removal of lignin and increase enzyme accessibility to the polysaccharides. 28439294 6 60 theme viable 1587:1592 arg1 process 1622:1628 an economically viable and sustainable biorefinery process 1571:1628 an economically viable and sustainable biorefinery process 1571:1628 CONCLUSION Our findings clearly demonstrate that the introduction of ester linkages into the lignin polymer backbone decreases biomass recalcitrance in poplar has the potential to reduce the energy and/or amount of IL required for effective pretreatment, and could enable the development of an economically viable and sustainable biorefinery process. 28439294 6 61 theme IL 1495:1496 arg1 energy 1471:1476 energy 1471:1476 energy 1471:1476 CONCLUSION Our findings clearly demonstrate that the introduction of ester linkages into the lignin polymer backbone decreases biomass recalcitrance in poplar has the potential to reduce the energy and/or amount of IL required for effective pretreatment, and could enable the development of an economically viable and sustainable biorefinery process. 28439294 3 62 dep " 741:741 arg1 i.e. 724:727 i.e. 724:727 i.e. 724:727 Here, transgenic poplar lines in which monolignol ferulate conjugates were synthesized during cell wall development to introduce, during lignification, readily cleavable ester linkages into the lignin polymer backbone (i.e., "zip lignin"), along with wild-type (WT) controls, were pretreated with different ionic liquids (ILs). 28439294 3 63 theme polymer 706:712 arg1 backbone 714:721 the lignin polymer backbone 695:721 the lignin polymer backbone (i.e., "zip lignin") 695:742 Here, transgenic poplar lines in which monolignol ferulate conjugates were synthesized during cell wall development to introduce, during lignification, readily cleavable ester linkages into the lignin polymer backbone (i.e., "zip lignin"), along with wild-type (WT) controls, were pretreated with different ionic liquids (ILs). 28439294 3 63 theme polymer 706:712 arg1 " 741:741 "zip lignin" 730:741 "zip lignin" 730:741 Here, transgenic poplar lines in which monolignol ferulate conjugates were synthesized during cell wall development to introduce, during lignification, readily cleavable ester linkages into the lignin polymer backbone (i.e., "zip lignin"), along with wild-type (WT) controls, were pretreated with different ionic liquids (ILs). 28439294 1 64 theme essential 124:132 arg1 step 134:137 an essential step 121:137 an essential step in lignocellulosic biofuel production 121:175 BACKGROUND Biomass pretreatment remains an essential step in lignocellulosic biofuel production, largely to facilitate the efficient removal of lignin and increase enzyme accessibility to the polysaccharides. 28439294 5 65 theme WT 1269:1270 arg1 plants 1272:1277 WT plants 1269:1277 WT plants 1269:1277 After pretreatment with any of three different ILs, and after limited saccharification, the transgenic poplars, especially those with relatively higher amounts of incorporated monolignol ferulate conjugates, yielded up to 23% higher sugar levels compared to WT plants. 28439294 1 66 theme lignin 225:230 arg1 removal 214:220 the efficient removal 200:220 the efficient removal of lignin 200:230 BACKGROUND Biomass pretreatment remains an essential step in lignocellulosic biofuel production, largely to facilitate the efficient removal of lignin and increase enzyme accessibility to the polysaccharides. 28439294 4 67 theme bonds 877:881 arg1 introduction 855:866 The strategic introduction 841:866 The strategic introduction of ester bonds into the lignin backbone 841:906 RESULTS The strategic introduction of ester bonds into the lignin backbone resulted in increased pretreatment efficiency and released more carbohydrates with lower energy input. 28439294 5 68 dep 23 1233:1234 arg1 to 1230:1231 to 1230:1231 to 1230:1231 After pretreatment with any of three different ILs, and after limited saccharification, the transgenic poplars, especially those with relatively higher amounts of incorporated monolignol ferulate conjugates, yielded up to 23% higher sugar levels compared to WT plants. 28439294 4 69 dep RESULTS 833:839 arg1 released 958:965 released 958:965 released more carbohydrates with lower energy input 958:1008 RESULTS The strategic introduction of ester bonds into the lignin backbone resulted in increased pretreatment efficiency and released more carbohydrates with lower energy input. 28439294 4 69 dep RESULTS 833:839 arg1 resulted 908:915 resulted 908:915 resulted in increased pretreatment efficiency 908:952 RESULTS The strategic introduction of ester bonds into the lignin backbone resulted in increased pretreatment efficiency and released more carbohydrates with lower energy input. 28439294 2 70 theme significant 323:333 arg1 efforts 335:341 significant efforts 323:341 significant efforts in planta 323:351 In recent years, there have been significant efforts in planta to reduce lignin content or modify its composition to overcome the inherent recalcitrance that it imposes on lignocellulosic biomass during processing. 28439294 5 71 theme different 1048:1056 arg1 ILs 1058:1060 three different ILs 1042:1060 three different ILs 1042:1060 After pretreatment with any of three different ILs, and after limited saccharification, the transgenic poplars, especially those with relatively higher amounts of incorporated monolignol ferulate conjugates, yielded up to 23% higher sugar levels compared to WT plants. 28439294 0 72 theme ionic 44:48 arg1 pretreatment 57:68 ionic liquid pretreatment 44:68 ionic liquid pretreatment of poplar 44:78 Impact of lignin polymer backbone esters on ionic liquid pretreatment of poplar. 28439294 5 73 theme transgenic 1103:1112 arg1 poplars 1114:1120 the transgenic poplars 1099:1120 the transgenic poplars 1099:1120 After pretreatment with any of three different ILs, and after limited saccharification, the transgenic poplars, especially those with relatively higher amounts of incorporated monolignol ferulate conjugates, yielded up to 23% higher sugar levels compared to WT plants. 28439294 5 73 theme transgenic 1103:1112 arg1 those 1134:1138 those 1134:1138 those 1134:1138 After pretreatment with any of three different ILs, and after limited saccharification, the transgenic poplars, especially those with relatively higher amounts of incorporated monolignol ferulate conjugates, yielded up to 23% higher sugar levels compared to WT plants. 28439294 2 74 theme lignin 363:368 arg1 content 370:376 lignin content 363:376 lignin content 363:376 In recent years, there have been significant efforts in planta to reduce lignin content or modify its composition to overcome the inherent recalcitrance that it imposes on lignocellulosic biomass during processing. 28439294 5 75 theme higher 1237:1242 arg1 levels 1250:1255 up to 23% higher sugar levels 1227:1255 up to 23% higher sugar levels 1227:1255 After pretreatment with any of three different ILs, and after limited saccharification, the transgenic poplars, especially those with relatively higher amounts of incorporated monolignol ferulate conjugates, yielded up to 23% higher sugar levels compared to WT plants. 28439294 1 76 theme enzyme 245:250 arg1 accessibility 252:264 enzyme accessibility 245:264 enzyme accessibility to the polysaccharides 245:287 BACKGROUND Biomass pretreatment remains an essential step in lignocellulosic biofuel production, largely to facilitate the efficient removal of lignin and increase enzyme accessibility to the polysaccharides. 30970832 2 0 theme used 323:326 arg1 flour 244:248 Defatted soy flour 231:248 Defatted soy flour (DSF) 231:254 Defatted soy flour (DSF), comprised of 50% protein and 40% carbohydrate, is the most widely used raw material for the preparation of soy-based adhesives that are unfortunately hampered by poor gluability and water resistance. 30970832 2 0 theme used 323:326 arg1 material 332:339 the most widely used raw material 307:339 the most widely used raw material for the preparation of soy-based adhesives that are unfortunately hampered by poor gluability and water resistance 307:454 Defatted soy flour (DSF), comprised of 50% protein and 40% carbohydrate, is the most widely used raw material for the preparation of soy-based adhesives that are unfortunately hampered by poor gluability and water resistance. 30970832 8 1 contain had 1396:1398 arg2 rate 1422:1425 a higher wood failure rate 1400:1425 a higher wood failure rate 1400:1425 Scanning electron microscopy (SEM) images showed that plywood bonded with SBA had a higher wood failure rate than controls. 30970832 8 1 contain had 1396:1398 arg1 plywood 1372:1378 plywood 1372:1378 plywood bonded with SBA 1372:1394 Scanning electron microscopy (SEM) images showed that plywood bonded with SBA had a higher wood failure rate than controls. 30970832 0 2 theme Carbohydrates 72:84 arg1 Hydrolysis 58:67 Acid Hydrolysis 53:67 Acid Hydrolysis of Carbohydrates 53:84 Development of Defatted Soy Flour-Based Adhesives by Acid Hydrolysis of Carbohydrates. 30970832 5 3 theme carbohydrates 781:793 arg1 effect 760:765 The effect 756:765 The effect of hydrolyzed carbohydrates on the performance of the SBA 756:823 The effect of hydrolyzed carbohydrates on the performance of the SBA was investigated, and hydrolyzed carbohydrates significantly increased the amount of reducing sugars, but decreased insoluble substances. 30970832 6 4 dep Fourier 963:969 arg1 transform 971:979 transform 971:979 transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) analyses 971:1060 Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) analyses revealed an enhanced cross-linking structure with fewer hydrophilic groups in cured SBAs. 30970832 6 5 from groups 1130:1135 arg1 SBAs 1146:1149 cured SBAs 1140:1149 cured SBAs 1140:1149 Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) analyses revealed an enhanced cross-linking structure with fewer hydrophilic groups in cured SBAs. 30970832 5 6 theme SBA 821:823 arg1 performance 802:812 the performance 798:812 the performance of the SBA 798:823 The effect of hydrolyzed carbohydrates on the performance of the SBA was investigated, and hydrolyzed carbohydrates significantly increased the amount of reducing sugars, but decreased insoluble substances. 30970832 6 7 dep transform 971:979 arg1 infrared 981:988 infrared 981:988 transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) analyses 971:1060 Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) analyses revealed an enhanced cross-linking structure with fewer hydrophilic groups in cured SBAs. 30970832 3 8 theme soy 561:563 arg1 flour-based 565:575 a formaldehyde-free defatted soy flour-based adhesive 532:584 a formaldehyde-free defatted soy flour-based adhesive (SBA) 532:590 In the present study, we developed a self-crosslinking approach to prepare a formaldehyde-free defatted soy flour-based adhesive (SBA). 30970832 3 8 theme soy 561:563 arg1 SBA 587:589 SBA 587:589 SBA 587:589 In the present study, we developed a self-crosslinking approach to prepare a formaldehyde-free defatted soy flour-based adhesive (SBA). 30970832 5 9 theme hydrolyzed 770:779 arg1 carbohydrates 781:793 hydrolyzed carbohydrates 770:793 hydrolyzed carbohydrates 770:793 The effect of hydrolyzed carbohydrates on the performance of the SBA was investigated, and hydrolyzed carbohydrates significantly increased the amount of reducing sugars, but decreased insoluble substances. 30970832 8 10 theme Scanning 1318:1325 arg1 SEM 1348:1350 SEM 1348:1350 SEM 1348:1350 Scanning electron microscopy (SEM) images showed that plywood bonded with SBA had a higher wood failure rate than controls. 30970832 8 10 theme Scanning 1318:1325 arg1 microscopy 1336:1345 Scanning electron microscopy 1318:1345 Scanning electron microscopy (SEM) images 1318:1358 Scanning electron microscopy (SEM) images showed that plywood bonded with SBA had a higher wood failure rate than controls. 30970832 3 11 theme formaldehyde-free 534:550 arg1 flour-based 565:575 a formaldehyde-free defatted soy flour-based adhesive 532:584 a formaldehyde-free defatted soy flour-based adhesive (SBA) 532:590 In the present study, we developed a self-crosslinking approach to prepare a formaldehyde-free defatted soy flour-based adhesive (SBA). 30970832 3 11 theme formaldehyde-free 534:550 arg1 SBA 587:589 SBA 587:589 SBA 587:589 In the present study, we developed a self-crosslinking approach to prepare a formaldehyde-free defatted soy flour-based adhesive (SBA). 30970832 9 12 theme other 1528:1532 arg1 resources 1542:1550 other natural resources 1528:1550 other natural resources with a similar polysaccharides and protein composition 1528:1605 This approach has potential for preparing bio-adhesives with enhanced properties from other natural resources with a similar polysaccharides and protein composition. 30970832 5 13 theme hydrolyzed 847:856 arg1 carbohydrates 858:870 hydrolyzed carbohydrates 847:870 hydrolyzed carbohydrates 847:870 The effect of hydrolyzed carbohydrates on the performance of the SBA was investigated, and hydrolyzed carbohydrates significantly increased the amount of reducing sugars, but decreased insoluble substances. 30970832 2 14 theme % 272:272 arg1 protein 274:280 50% protein 270:280 50% protein 270:280 Defatted soy flour (DSF), comprised of 50% protein and 40% carbohydrate, is the most widely used raw material for the preparation of soy-based adhesives that are unfortunately hampered by poor gluability and water resistance. 30970832 3 15 theme defatted 552:559 arg1 flour-based 565:575 a formaldehyde-free defatted soy flour-based adhesive 532:584 a formaldehyde-free defatted soy flour-based adhesive (SBA) 532:590 In the present study, we developed a self-crosslinking approach to prepare a formaldehyde-free defatted soy flour-based adhesive (SBA). 30970832 3 15 theme defatted 552:559 arg1 SBA 587:589 SBA 587:589 SBA 587:589 In the present study, we developed a self-crosslinking approach to prepare a formaldehyde-free defatted soy flour-based adhesive (SBA). 30970832 7 16 theme better 1239:1244 arg1 gluability 1246:1255 better gluability 1239:1255 better gluability 1239:1255 Maillard reactions between hydrolyzed carbohydrates and proteins resulted in SBAs with better gluability, rheological properties and thermal stability than controls. 30970832 2 17 theme 50 270:271 arg1 % 272:272 % 272:272 % 272:272 Defatted soy flour (DSF), comprised of 50% protein and 40% carbohydrate, is the most widely used raw material for the preparation of soy-based adhesives that are unfortunately hampered by poor gluability and water resistance. 30970832 7 18 theme rheological 1258:1268 arg1 properties 1270:1279 rheological properties 1258:1279 rheological properties 1258:1279 Maillard reactions between hydrolyzed carbohydrates and proteins resulted in SBAs with better gluability, rheological properties and thermal stability than controls. 30970832 9 19 with resources 1542:1550 arg1 polysaccharides 1567:1581 a similar polysaccharides 1557:1581 a similar polysaccharides 1557:1581 This approach has potential for preparing bio-adhesives with enhanced properties from other natural resources with a similar polysaccharides and protein composition. 30970832 9 19 with resources 1542:1550 arg1 composition 1595:1605 protein composition 1587:1605 protein composition 1587:1605 This approach has potential for preparing bio-adhesives with enhanced properties from other natural resources with a similar polysaccharides and protein composition. 30970832 9 20 theme similar 1559:1565 arg1 polysaccharides 1567:1581 a similar polysaccharides 1557:1581 a similar polysaccharides 1557:1581 This approach has potential for preparing bio-adhesives with enhanced properties from other natural resources with a similar polysaccharides and protein composition. 30970832 3 21 theme self-crosslinking 494:510 arg1 approach 512:519 a self-crosslinking approach 492:519 a self-crosslinking approach to prepare a formaldehyde-free defatted soy flour-based adhesive (SBA) 492:590 In the present study, we developed a self-crosslinking approach to prepare a formaldehyde-free defatted soy flour-based adhesive (SBA). 30970832 1 22 theme renewable 178:186 arg1 they 167:170 they 167:170 they 167:170 Soy-based adhesives are attracting increasing attention in recent years because they are a renewable and environmentally friendly raw material. 30970832 1 22 theme renewable 178:186 arg1 material 221:228 a renewable and environmentally friendly raw material 176:228 a renewable and environmentally friendly raw material 176:228 Soy-based adhesives are attracting increasing attention in recent years because they are a renewable and environmentally friendly raw material. 30970832 2 23 theme poor 419:422 arg1 gluability 424:433 poor gluability 419:433 poor gluability 419:433 Defatted soy flour (DSF), comprised of 50% protein and 40% carbohydrate, is the most widely used raw material for the preparation of soy-based adhesives that are unfortunately hampered by poor gluability and water resistance. 30970832 7 24 theme hydrolyzed 1179:1188 arg1 carbohydrates 1190:1202 hydrolyzed carbohydrates 1179:1202 hydrolyzed carbohydrates 1179:1202 Maillard reactions between hydrolyzed carbohydrates and proteins resulted in SBAs with better gluability, rheological properties and thermal stability than controls. 30970832 1 25 theme Soy-based 87:95 arg1 adhesives 97:105 Soy-based adhesives 87:105 Soy-based adhesives 87:105 Soy-based adhesives are attracting increasing attention in recent years because they are a renewable and environmentally friendly raw material. 30970832 9 26 theme natural 1534:1540 arg1 resources 1542:1550 other natural resources 1528:1550 other natural resources with a similar polysaccharides and protein composition 1528:1605 This approach has potential for preparing bio-adhesives with enhanced properties from other natural resources with a similar polysaccharides and protein composition. 30970832 2 27 theme % 288:288 arg1 carbohydrate 290:301 40% carbohydrate 286:301 40% carbohydrate 286:301 Defatted soy flour (DSF), comprised of 50% protein and 40% carbohydrate, is the most widely used raw material for the preparation of soy-based adhesives that are unfortunately hampered by poor gluability and water resistance. 30970832 7 28 with SBAs 1229:1232 arg1 stability 1293:1301 thermal stability 1285:1301 thermal stability 1285:1301 Maillard reactions between hydrolyzed carbohydrates and proteins resulted in SBAs with better gluability, rheological properties and thermal stability than controls. 30970832 7 28 with SBAs 1229:1232 arg1 gluability 1246:1255 better gluability 1239:1255 better gluability 1239:1255 Maillard reactions between hydrolyzed carbohydrates and proteins resulted in SBAs with better gluability, rheological properties and thermal stability than controls. 30970832 7 28 with SBAs 1229:1232 arg1 properties 1270:1279 rheological properties 1258:1279 rheological properties 1258:1279 Maillard reactions between hydrolyzed carbohydrates and proteins resulted in SBAs with better gluability, rheological properties and thermal stability than controls. 30970832 1 29 theme environmentally 192:206 arg1 they 167:170 they 167:170 they 167:170 Soy-based adhesives are attracting increasing attention in recent years because they are a renewable and environmentally friendly raw material. 30970832 1 29 theme environmentally 192:206 arg1 material 221:228 a renewable and environmentally friendly raw material 176:228 a renewable and environmentally friendly raw material 176:228 Soy-based adhesives are attracting increasing attention in recent years because they are a renewable and environmentally friendly raw material. 30970832 0 30 theme Soy 24:26 arg1 Flour-Based 28:38 Defatted Soy Flour-Based 15:38 Defatted Soy Flour-Based 15:38 Development of Defatted Soy Flour-Based Adhesives by Acid Hydrolysis of Carbohydrates. 30970832 1 31 from attention 133:141 arg1 years 153:157 recent years 146:157 recent years because they are a renewable and environmentally friendly raw material 146:228 Soy-based adhesives are attracting increasing attention in recent years because they are a renewable and environmentally friendly raw material. 30970832 2 32 theme 40 286:287 arg1 % 288:288 % 288:288 % 288:288 Defatted soy flour (DSF), comprised of 50% protein and 40% carbohydrate, is the most widely used raw material for the preparation of soy-based adhesives that are unfortunately hampered by poor gluability and water resistance. 30970832 5 33 theme reducing 910:917 arg1 sugars 919:924 reducing sugars 910:924 reducing sugars 910:924 The effect of hydrolyzed carbohydrates on the performance of the SBA was investigated, and hydrolyzed carbohydrates significantly increased the amount of reducing sugars, but decreased insoluble substances. 30970832 1 34 theme friendly 208:215 arg1 they 167:170 they 167:170 they 167:170 Soy-based adhesives are attracting increasing attention in recent years because they are a renewable and environmentally friendly raw material. 30970832 1 34 theme friendly 208:215 arg1 material 221:228 a renewable and environmentally friendly raw material 176:228 a renewable and environmentally friendly raw material 176:228 Soy-based adhesives are attracting increasing attention in recent years because they are a renewable and environmentally friendly raw material. 30970832 0 35 theme Defatted 15:22 arg1 Flour-Based 28:38 Defatted Soy Flour-Based 15:38 Defatted Soy Flour-Based 15:38 Development of Defatted Soy Flour-Based Adhesives by Acid Hydrolysis of Carbohydrates. 30970832 6 36 with structure 1097:1105 arg1 groups 1130:1135 fewer hydrophilic groups 1112:1135 fewer hydrophilic groups in cured SBAs 1112:1149 Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) analyses revealed an enhanced cross-linking structure with fewer hydrophilic groups in cured SBAs. 30970832 6 37 theme enhanced 1074:1081 arg1 structure 1097:1105 an enhanced cross-linking structure 1071:1105 an enhanced cross-linking structure with fewer hydrophilic groups in cured SBAs 1071:1149 Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) analyses revealed an enhanced cross-linking structure with fewer hydrophilic groups in cured SBAs. 30970832 6 38 dep spectroscopy 990:1001 arg1 analyses 1053:1060 analyses 1053:1060 analyses 1053:1060 Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) analyses revealed an enhanced cross-linking structure with fewer hydrophilic groups in cured SBAs. 30970832 1 39 theme raw 217:219 arg1 they 167:170 they 167:170 they 167:170 Soy-based adhesives are attracting increasing attention in recent years because they are a renewable and environmentally friendly raw material. 30970832 1 39 theme raw 217:219 arg1 material 221:228 a renewable and environmentally friendly raw material 176:228 a renewable and environmentally friendly raw material 176:228 Soy-based adhesives are attracting increasing attention in recent years because they are a renewable and environmentally friendly raw material. 30970832 9 40 with bio-adhesives 1484:1496 arg1 properties 1512:1521 enhanced properties 1503:1521 enhanced properties from other natural resources with a similar polysaccharides and protein composition 1503:1605 This approach has potential for preparing bio-adhesives with enhanced properties from other natural resources with a similar polysaccharides and protein composition. 30970832 9 41 theme enhanced 1503:1510 arg1 properties 1512:1521 enhanced properties 1503:1521 enhanced properties from other natural resources with a similar polysaccharides and protein composition 1503:1605 This approach has potential for preparing bio-adhesives with enhanced properties from other natural resources with a similar polysaccharides and protein composition. 30970832 6 42 theme cured 1140:1144 arg1 SBAs 1146:1149 cured SBAs 1140:1149 cured SBAs 1140:1149 Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) analyses revealed an enhanced cross-linking structure with fewer hydrophilic groups in cured SBAs. 30970832 3 43 theme adhesive 577:584 arg1 flour-based 565:575 a formaldehyde-free defatted soy flour-based adhesive 532:584 a formaldehyde-free defatted soy flour-based adhesive (SBA) 532:590 In the present study, we developed a self-crosslinking approach to prepare a formaldehyde-free defatted soy flour-based adhesive (SBA). 30970832 3 43 theme adhesive 577:584 arg1 SBA 587:589 SBA 587:589 SBA 587:589 In the present study, we developed a self-crosslinking approach to prepare a formaldehyde-free defatted soy flour-based adhesive (SBA). 30970832 9 44 from resources 1542:1550 arg1 properties 1512:1521 enhanced properties 1503:1521 enhanced properties from other natural resources with a similar polysaccharides and protein composition 1503:1605 This approach has potential for preparing bio-adhesives with enhanced properties from other natural resources with a similar polysaccharides and protein composition. 30970832 2 45 theme adhesives 374:382 arg1 preparation 349:359 the preparation 345:359 the preparation of soy-based adhesives that are unfortunately hampered by poor gluability and water resistance 345:454 Defatted soy flour (DSF), comprised of 50% protein and 40% carbohydrate, is the most widely used raw material for the preparation of soy-based adhesives that are unfortunately hampered by poor gluability and water resistance. 30970832 2 46 theme water 439:443 arg1 resistance 445:454 water resistance 439:454 water resistance 439:454 Defatted soy flour (DSF), comprised of 50% protein and 40% carbohydrate, is the most widely used raw material for the preparation of soy-based adhesives that are unfortunately hampered by poor gluability and water resistance. 30970832 0 47 theme Flour-Based 28:38 arg1 Development 0:10 Development 0:10 Development of Defatted Soy Flour-Based 0:38 Development of Defatted Soy Flour-Based Adhesives by Acid Hydrolysis of Carbohydrates. 30970832 5 48 theme sugars 919:924 arg1 amount 900:905 the amount 896:905 the amount of reducing sugars 896:924 The effect of hydrolyzed carbohydrates on the performance of the SBA was investigated, and hydrolyzed carbohydrates significantly increased the amount of reducing sugars, but decreased insoluble substances. 30970832 5 48 theme sugars 919:924 arg1 sugars 919:924 reducing sugars 910:924 reducing sugars 910:924 The effect of hydrolyzed carbohydrates on the performance of the SBA was investigated, and hydrolyzed carbohydrates significantly increased the amount of reducing sugars, but decreased insoluble substances. 30970832 2 49 theme soy-based 364:372 arg1 adhesives 374:382 soy-based adhesives 364:382 soy-based adhesives that are unfortunately hampered by poor gluability and water resistance 364:454 Defatted soy flour (DSF), comprised of 50% protein and 40% carbohydrate, is the most widely used raw material for the preparation of soy-based adhesives that are unfortunately hampered by poor gluability and water resistance. 30970832 0 50 theme Acid 53:56 arg1 Hydrolysis 58:67 Acid Hydrolysis 53:67 Acid Hydrolysis of Carbohydrates 53:84 Development of Defatted Soy Flour-Based Adhesives by Acid Hydrolysis of Carbohydrates. 30970832 2 51 theme soy 240:242 arg1 flour 244:248 Defatted soy flour 231:248 Defatted soy flour (DSF) 231:254 Defatted soy flour (DSF), comprised of 50% protein and 40% carbohydrate, is the most widely used raw material for the preparation of soy-based adhesives that are unfortunately hampered by poor gluability and water resistance. 30970832 2 51 theme soy 240:242 arg1 DSF 251:253 DSF 251:253 DSF 251:253 Defatted soy flour (DSF), comprised of 50% protein and 40% carbohydrate, is the most widely used raw material for the preparation of soy-based adhesives that are unfortunately hampered by poor gluability and water resistance. 30970832 2 51 theme soy 240:242 arg1 material 332:339 the most widely used raw material 307:339 the most widely used raw material for the preparation of soy-based adhesives that are unfortunately hampered by poor gluability and water resistance 307:454 Defatted soy flour (DSF), comprised of 50% protein and 40% carbohydrate, is the most widely used raw material for the preparation of soy-based adhesives that are unfortunately hampered by poor gluability and water resistance. 30970832 1 52 theme increasing 122:131 arg1 attention 133:141 increasing attention 122:141 increasing attention in recent years because they are a renewable and environmentally friendly raw material 122:228 Soy-based adhesives are attracting increasing attention in recent years because they are a renewable and environmentally friendly raw material. 30970832 6 53 theme cross-linking 1083:1095 arg1 structure 1097:1105 an enhanced cross-linking structure 1071:1105 an enhanced cross-linking structure with fewer hydrophilic groups in cured SBAs 1071:1149 Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) analyses revealed an enhanced cross-linking structure with fewer hydrophilic groups in cured SBAs. 30970832 9 54 contain has 1456:1458 arg2 potential 1460:1468 potential 1460:1468 potential for preparing bio-adhesives with enhanced properties from other natural resources with a similar polysaccharides and protein composition 1460:1605 This approach has potential for preparing bio-adhesives with enhanced properties from other natural resources with a similar polysaccharides and protein composition. 30970832 9 54 contain has 1456:1458 arg1 approach 1447:1454 This approach 1442:1454 This approach 1442:1454 This approach has potential for preparing bio-adhesives with enhanced properties from other natural resources with a similar polysaccharides and protein composition. 30970832 8 55 theme higher 1402:1407 arg1 rate 1422:1425 a higher wood failure rate 1400:1425 a higher wood failure rate 1400:1425 Scanning electron microscopy (SEM) images showed that plywood bonded with SBA had a higher wood failure rate than controls. 30970832 2 56 theme Defatted 231:238 arg1 flour 244:248 Defatted soy flour 231:248 Defatted soy flour (DSF) 231:254 Defatted soy flour (DSF), comprised of 50% protein and 40% carbohydrate, is the most widely used raw material for the preparation of soy-based adhesives that are unfortunately hampered by poor gluability and water resistance. 30970832 2 56 theme Defatted 231:238 arg1 DSF 251:253 DSF 251:253 DSF 251:253 Defatted soy flour (DSF), comprised of 50% protein and 40% carbohydrate, is the most widely used raw material for the preparation of soy-based adhesives that are unfortunately hampered by poor gluability and water resistance. 30970832 2 56 theme Defatted 231:238 arg1 material 332:339 the most widely used raw material 307:339 the most widely used raw material for the preparation of soy-based adhesives that are unfortunately hampered by poor gluability and water resistance 307:454 Defatted soy flour (DSF), comprised of 50% protein and 40% carbohydrate, is the most widely used raw material for the preparation of soy-based adhesives that are unfortunately hampered by poor gluability and water resistance. 30970832 3 57 theme present 464:470 arg1 study 472:476 the present study 460:476 the present study 460:476 In the present study, we developed a self-crosslinking approach to prepare a formaldehyde-free defatted soy flour-based adhesive (SBA). 30970832 7 58 theme thermal 1285:1291 arg1 stability 1293:1301 thermal stability 1285:1301 thermal stability 1285:1301 Maillard reactions between hydrolyzed carbohydrates and proteins resulted in SBAs with better gluability, rheological properties and thermal stability than controls. 30970832 5 59 theme insoluble 941:949 arg1 substances 951:960 insoluble substances 941:960 insoluble substances 941:960 The effect of hydrolyzed carbohydrates on the performance of the SBA was investigated, and hydrolyzed carbohydrates significantly increased the amount of reducing sugars, but decreased insoluble substances. 30970832 4 60 dep % 640:640 arg1 acid 699:702 hydrochloric acid 686:702 hydrochloric acid 686:702 Carbohydrates in the DSF were hydrolyzed with 0% (controls), 0.5%, 1.0%, 2.0%, 3.0% and 5.0% hydrochloric acid, and cross-linked with proteins to prepare the SBA. 30970832 8 61 theme microscopy 1336:1345 arg1 images 1353:1358 Scanning electron microscopy (SEM) images 1318:1358 Scanning electron microscopy (SEM) images 1318:1358 Scanning electron microscopy (SEM) images showed that plywood bonded with SBA had a higher wood failure rate than controls. 30970832 6 62 theme photoelectron 1020:1032 arg1 XPS 1048:1050 XPS 1048:1050 XPS 1048:1050 Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) analyses revealed an enhanced cross-linking structure with fewer hydrophilic groups in cured SBAs. 30970832 6 62 theme photoelectron 1020:1032 arg1 spectroscopy 1034:1045 X-ray photoelectron spectroscopy 1014:1045 X-ray photoelectron spectroscopy (XPS) 1014:1051 Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) analyses revealed an enhanced cross-linking structure with fewer hydrophilic groups in cured SBAs. 30970832 1 63 dep years 153:157 arg1 they 167:170 they 167:170 they 167:170 Soy-based adhesives are attracting increasing attention in recent years because they are a renewable and environmentally friendly raw material. 30970832 1 63 dep years 153:157 arg1 material 221:228 a renewable and environmentally friendly raw material 176:228 a renewable and environmentally friendly raw material 176:228 Soy-based adhesives are attracting increasing attention in recent years because they are a renewable and environmentally friendly raw material. 30970832 6 64 theme X-ray 1014:1018 arg1 XPS 1048:1050 XPS 1048:1050 XPS 1048:1050 Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) analyses revealed an enhanced cross-linking structure with fewer hydrophilic groups in cured SBAs. 30970832 6 64 theme X-ray 1014:1018 arg1 spectroscopy 1034:1045 X-ray photoelectron spectroscopy 1014:1045 X-ray photoelectron spectroscopy (XPS) 1014:1051 Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) analyses revealed an enhanced cross-linking structure with fewer hydrophilic groups in cured SBAs. 30970832 8 65 theme failure 1414:1420 arg1 rate 1422:1425 a higher wood failure rate 1400:1425 a higher wood failure rate 1400:1425 Scanning electron microscopy (SEM) images showed that plywood bonded with SBA had a higher wood failure rate than controls. 30970832 6 66 theme hydrophilic 1118:1128 arg1 groups 1130:1135 fewer hydrophilic groups 1112:1135 fewer hydrophilic groups in cured SBAs 1112:1149 Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) analyses revealed an enhanced cross-linking structure with fewer hydrophilic groups in cured SBAs. 30970832 1 67 theme recent 146:151 arg1 years 153:157 recent years 146:157 recent years because they are a renewable and environmentally friendly raw material 146:228 Soy-based adhesives are attracting increasing attention in recent years because they are a renewable and environmentally friendly raw material. 30970832 4 68 from Carbohydrates 593:605 arg1 DSF 614:616 the DSF 610:616 the DSF 610:616 Carbohydrates in the DSF were hydrolyzed with 0% (controls), 0.5%, 1.0%, 2.0%, 3.0% and 5.0% hydrochloric acid, and cross-linked with proteins to prepare the SBA. 30970832 8 69 theme wood 1409:1412 arg1 rate 1422:1425 a higher wood failure rate 1400:1425 a higher wood failure rate 1400:1425 Scanning electron microscopy (SEM) images showed that plywood bonded with SBA had a higher wood failure rate than controls. 30970832 6 70 theme fewer 1112:1116 arg1 groups 1130:1135 fewer hydrophilic groups 1112:1135 fewer hydrophilic groups in cured SBAs 1112:1149 Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) analyses revealed an enhanced cross-linking structure with fewer hydrophilic groups in cured SBAs. 30970832 5 71 from effect 760:765 arg1 performance 802:812 the performance 798:812 the performance of the SBA 798:823 The effect of hydrolyzed carbohydrates on the performance of the SBA was investigated, and hydrolyzed carbohydrates significantly increased the amount of reducing sugars, but decreased insoluble substances. 30970832 8 72 theme electron 1327:1334 arg1 SEM 1348:1350 SEM 1348:1350 SEM 1348:1350 Scanning electron microscopy (SEM) images showed that plywood bonded with SBA had a higher wood failure rate than controls. 30970832 8 72 theme electron 1327:1334 arg1 microscopy 1336:1345 Scanning electron microscopy 1318:1345 Scanning electron microscopy (SEM) images 1318:1358 Scanning electron microscopy (SEM) images showed that plywood bonded with SBA had a higher wood failure rate than controls. 30970832 4 73 theme hydrochloric 686:697 arg1 acid 699:702 hydrochloric acid 686:702 hydrochloric acid 686:702 Carbohydrates in the DSF were hydrolyzed with 0% (controls), 0.5%, 1.0%, 2.0%, 3.0% and 5.0% hydrochloric acid, and cross-linked with proteins to prepare the SBA. 30970832 2 74 theme raw 328:330 arg1 flour 244:248 Defatted soy flour 231:248 Defatted soy flour (DSF) 231:254 Defatted soy flour (DSF), comprised of 50% protein and 40% carbohydrate, is the most widely used raw material for the preparation of soy-based adhesives that are unfortunately hampered by poor gluability and water resistance. 30970832 2 74 theme raw 328:330 arg1 material 332:339 the most widely used raw material 307:339 the most widely used raw material for the preparation of soy-based adhesives that are unfortunately hampered by poor gluability and water resistance 307:454 Defatted soy flour (DSF), comprised of 50% protein and 40% carbohydrate, is the most widely used raw material for the preparation of soy-based adhesives that are unfortunately hampered by poor gluability and water resistance. 30970832 7 75 theme Maillard 1152:1159 arg1 reactions 1161:1169 Maillard reactions 1152:1169 Maillard reactions between hydrolyzed carbohydrates and proteins 1152:1215 Maillard reactions between hydrolyzed carbohydrates and proteins resulted in SBAs with better gluability, rheological properties and thermal stability than controls. 30970832 9 76 theme protein 1587:1593 arg1 composition 1595:1605 protein composition 1587:1605 protein composition 1587:1605 This approach has potential for preparing bio-adhesives with enhanced properties from other natural resources with a similar polysaccharides and protein composition. 28289404 9 0 from importance 1925:1934 arg1 processing 1961:1970 processing 1961:1970 processing this abundant pool of organic carbon 1961:2007 These differential effects of EPS fractions on carbon-loss rates, nutrient regeneration and microbial community assembly improve our understanding of coastal-sediment carbon cycling and demonstrate the importance of diverse microbiota in processing this abundant pool of organic carbon. 28289404 6 1 theme dissolved 1135:1143 arg1 nitrogen 1145:1152 dissolved nitrogen 1135:1152 dissolved nitrogen 1135:1152 Addition of hot-bicarbonate-EPS resulted in large increases in dissolved nitrogen and phosphorous by the end of the experiment, indicating that the more complex EPS is an important source of regenerated inorganic nutrients. 28289404 2 2 theme carbon 405:410 arg1 pool 412:415 a substantial carbon pool 391:415 a substantial carbon pool 391:415 Such microphytobenthic (MPB) diatoms exude large quantities of extracellular polymeric substances (EPS) comprising polysaccharides, glycoproteins and other biopolymers, which represent a substantial carbon pool. 28289404 7 3 theme bacterial 1462:1470 arg1 composition 1482:1492 the bacterial community composition 1458:1492 the bacterial community composition (from 0 to 9 days) 1458:1511 Microbial biomass increased ~4-6-fold over 9 days, and pyrosequencing of bacterial 16S rRNA genes revealed that the addition of both types of EPS greatly altered the bacterial community composition (from 0 to 9 days) compared to a control with no added EPS. 28289404 4 4 theme EPS 649:651 arg1 sources 660:666 two different EPS carbon sources 635:666 two different EPS carbon sources from a diatom-dominated biofilm: colloidal EPS (cEPS) and the more complex hot-bicarbonate-extracted EPS 635:771 An aerobic mudflat-sediment slurry experiment was performed in the dark with two different EPS carbon sources from a diatom-dominated biofilm: colloidal EPS (cEPS) and the more complex hot-bicarbonate-extracted EPS. 28289404 4 4 theme EPS 649:651 arg1 EPS 711:713 colloidal EPS 701:713 colloidal EPS (cEPS) 701:720 An aerobic mudflat-sediment slurry experiment was performed in the dark with two different EPS carbon sources from a diatom-dominated biofilm: colloidal EPS (cEPS) and the more complex hot-bicarbonate-extracted EPS. 28289404 4 4 theme EPS 649:651 arg1 EPS 769:771 the more complex hot-bicarbonate-extracted EPS 726:771 the more complex hot-bicarbonate-extracted EPS 726:771 An aerobic mudflat-sediment slurry experiment was performed in the dark with two different EPS carbon sources from a diatom-dominated biofilm: colloidal EPS (cEPS) and the more complex hot-bicarbonate-extracted EPS. 28289404 2 5 gly glycoproteins 338:350 arg1 glycoproteins 338:350 glycoproteins 338:350 glycoproteins 338:350 Such microphytobenthic (MPB) diatoms exude large quantities of extracellular polymeric substances (EPS) comprising polysaccharides, glycoproteins and other biopolymers, which represent a substantial carbon pool. 28289404 6 6 from increases 1122:1130 arg1 nitrogen 1145:1152 dissolved nitrogen 1135:1152 dissolved nitrogen 1135:1152 Addition of hot-bicarbonate-EPS resulted in large increases in dissolved nitrogen and phosphorous by the end of the experiment, indicating that the more complex EPS is an important source of regenerated inorganic nutrients. 28289404 9 7 theme organic 1994:2000 arg1 carbon 2002:2007 organic carbon 1994:2007 organic carbon 1994:2007 These differential effects of EPS fractions on carbon-loss rates, nutrient regeneration and microbial community assembly improve our understanding of coastal-sediment carbon cycling and demonstrate the importance of diverse microbiota in processing this abundant pool of organic carbon. 28289404 9 8 theme differential 1729:1740 arg1 effects 1742:1748 These differential effects 1723:1748 These differential effects of EPS fractions on carbon-loss rates, nutrient regeneration and microbial community assembly 1723:1842 These differential effects of EPS fractions on carbon-loss rates, nutrient regeneration and microbial community assembly improve our understanding of coastal-sediment carbon cycling and demonstrate the importance of diverse microbiota in processing this abundant pool of organic carbon. 28289404 7 9 theme EPS 1438:1440 arg1 types 1429:1433 both types 1424:1433 both types of EPS 1424:1440 Microbial biomass increased ~4-6-fold over 9 days, and pyrosequencing of bacterial 16S rRNA genes revealed that the addition of both types of EPS greatly altered the bacterial community composition (from 0 to 9 days) compared to a control with no added EPS. 28289404 6 10 theme inorganic 1275:1283 arg1 nutrients 1285:1293 regenerated inorganic nutrients 1263:1293 regenerated inorganic nutrients 1263:1293 Addition of hot-bicarbonate-EPS resulted in large increases in dissolved nitrogen and phosphorous by the end of the experiment, indicating that the more complex EPS is an important source of regenerated inorganic nutrients. 28289404 9 11 from effects 1742:1748 arg1 rates 1782:1786 carbon-loss rates 1770:1786 carbon-loss rates 1770:1786 These differential effects of EPS fractions on carbon-loss rates, nutrient regeneration and microbial community assembly improve our understanding of coastal-sediment carbon cycling and demonstrate the importance of diverse microbiota in processing this abundant pool of organic carbon. 28289404 9 11 from effects 1742:1748 arg1 regeneration 1798:1809 nutrient regeneration 1789:1809 nutrient regeneration 1789:1809 These differential effects of EPS fractions on carbon-loss rates, nutrient regeneration and microbial community assembly improve our understanding of coastal-sediment carbon cycling and demonstrate the importance of diverse microbiota in processing this abundant pool of organic carbon. 28289404 9 11 from effects 1742:1748 arg1 assembly 1835:1842 microbial community assembly 1815:1842 microbial community assembly 1815:1842 These differential effects of EPS fractions on carbon-loss rates, nutrient regeneration and microbial community assembly improve our understanding of coastal-sediment carbon cycling and demonstrate the importance of diverse microbiota in processing this abundant pool of organic carbon. 28289404 7 12 theme types 1429:1433 arg1 addition 1412:1419 the addition 1408:1419 the addition of both types of EPS 1408:1440 Microbial biomass increased ~4-6-fold over 9 days, and pyrosequencing of bacterial 16S rRNA genes revealed that the addition of both types of EPS greatly altered the bacterial community composition (from 0 to 9 days) compared to a control with no added EPS. 28289404 4 13 from biofilm 692:698 arg1 sources 660:666 two different EPS carbon sources 635:666 two different EPS carbon sources from a diatom-dominated biofilm: colloidal EPS (cEPS) and the more complex hot-bicarbonate-extracted EPS 635:771 An aerobic mudflat-sediment slurry experiment was performed in the dark with two different EPS carbon sources from a diatom-dominated biofilm: colloidal EPS (cEPS) and the more complex hot-bicarbonate-extracted EPS. 28289404 4 13 from biofilm 692:698 arg1 EPS 711:713 colloidal EPS 701:713 colloidal EPS (cEPS) 701:720 An aerobic mudflat-sediment slurry experiment was performed in the dark with two different EPS carbon sources from a diatom-dominated biofilm: colloidal EPS (cEPS) and the more complex hot-bicarbonate-extracted EPS. 28289404 4 13 from biofilm 692:698 arg1 EPS 769:771 the more complex hot-bicarbonate-extracted EPS 726:771 the more complex hot-bicarbonate-extracted EPS 726:771 An aerobic mudflat-sediment slurry experiment was performed in the dark with two different EPS carbon sources from a diatom-dominated biofilm: colloidal EPS (cEPS) and the more complex hot-bicarbonate-extracted EPS. 28289404 5 14 theme total 886:890 arg1 carbohydrates 892:904 total carbohydrates 886:904 total carbohydrates (TCHO) 886:911 Degradation rate constants determined over 9 days for three sediment fractions [dissolved organic carbon (DOC), total carbohydrates (TCHO), and (cEPS)] were generally higher in the colloidal-EPS slurries (0.105-0.123 d-1) compared with the hot-bicarbonate-extracted-EPS slurries (0.060-0.096 d-1). 28289404 5 14 theme total 886:890 arg1 TCHO 907:910 TCHO 907:910 TCHO 907:910 Degradation rate constants determined over 9 days for three sediment fractions [dissolved organic carbon (DOC), total carbohydrates (TCHO), and (cEPS)] were generally higher in the colloidal-EPS slurries (0.105-0.123 d-1) compared with the hot-bicarbonate-extracted-EPS slurries (0.060-0.096 d-1). 28289404 9 15 theme fractions 1757:1765 arg1 effects 1742:1748 These differential effects 1723:1748 These differential effects of EPS fractions on carbon-loss rates, nutrient regeneration and microbial community assembly 1723:1842 These differential effects of EPS fractions on carbon-loss rates, nutrient regeneration and microbial community assembly improve our understanding of coastal-sediment carbon cycling and demonstrate the importance of diverse microbiota in processing this abundant pool of organic carbon. 28289404 6 16 theme regenerated 1263:1273 arg1 nutrients 1285:1293 regenerated inorganic nutrients 1263:1293 regenerated inorganic nutrients 1263:1293 Addition of hot-bicarbonate-EPS resulted in large increases in dissolved nitrogen and phosphorous by the end of the experiment, indicating that the more complex EPS is an important source of regenerated inorganic nutrients. 28289404 4 17 theme colloidal 701:709 arg1 sources 660:666 two different EPS carbon sources 635:666 two different EPS carbon sources from a diatom-dominated biofilm: colloidal EPS (cEPS) and the more complex hot-bicarbonate-extracted EPS 635:771 An aerobic mudflat-sediment slurry experiment was performed in the dark with two different EPS carbon sources from a diatom-dominated biofilm: colloidal EPS (cEPS) and the more complex hot-bicarbonate-extracted EPS. 28289404 4 17 theme colloidal 701:709 arg1 cEPS 716:719 cEPS 716:719 cEPS 716:719 An aerobic mudflat-sediment slurry experiment was performed in the dark with two different EPS carbon sources from a diatom-dominated biofilm: colloidal EPS (cEPS) and the more complex hot-bicarbonate-extracted EPS. 28289404 4 17 theme colloidal 701:709 arg1 EPS 711:713 colloidal EPS 701:713 colloidal EPS (cEPS) 701:720 An aerobic mudflat-sediment slurry experiment was performed in the dark with two different EPS carbon sources from a diatom-dominated biofilm: colloidal EPS (cEPS) and the more complex hot-bicarbonate-extracted EPS. 28289404 5 18 theme Degradation 774:784 arg1 constants 791:799 Degradation rate constants 774:799 Degradation rate constants determined over 9 days for three sediment fractions [dissolved organic carbon (DOC), total carbohydrates (TCHO), and (cEPS)] 774:924 Degradation rate constants determined over 9 days for three sediment fractions [dissolved organic carbon (DOC), total carbohydrates (TCHO), and (cEPS)] were generally higher in the colloidal-EPS slurries (0.105-0.123 d-1) compared with the hot-bicarbonate-extracted-EPS slurries (0.060-0.096 d-1). 28289404 2 19 theme extracellular 269:281 arg1 EPS 305:307 EPS 305:307 EPS 305:307 Such microphytobenthic (MPB) diatoms exude large quantities of extracellular polymeric substances (EPS) comprising polysaccharides, glycoproteins and other biopolymers, which represent a substantial carbon pool. 28289404 2 19 theme extracellular 269:281 arg1 substances 293:302 extracellular polymeric substances 269:302 extracellular polymeric substances (EPS) comprising polysaccharides, glycoproteins and other biopolymers 269:372 Such microphytobenthic (MPB) diatoms exude large quantities of extracellular polymeric substances (EPS) comprising polysaccharides, glycoproteins and other biopolymers, which represent a substantial carbon pool. 28289404 7 20 from days 1507:1510 arg1 composition 1482:1492 the bacterial community composition 1458:1492 the bacterial community composition (from 0 to 9 days) 1458:1511 Microbial biomass increased ~4-6-fold over 9 days, and pyrosequencing of bacterial 16S rRNA genes revealed that the addition of both types of EPS greatly altered the bacterial community composition (from 0 to 9 days) compared to a control with no added EPS. 28289404 9 21 theme carbon-loss 1770:1780 arg1 rates 1782:1786 carbon-loss rates 1770:1786 carbon-loss rates 1770:1786 These differential effects of EPS fractions on carbon-loss rates, nutrient regeneration and microbial community assembly improve our understanding of coastal-sediment carbon cycling and demonstrate the importance of diverse microbiota in processing this abundant pool of organic carbon. 28289404 9 21 theme carbon-loss 1770:1780 arg1 regeneration 1798:1809 nutrient regeneration 1789:1809 nutrient regeneration 1789:1809 These differential effects of EPS fractions on carbon-loss rates, nutrient regeneration and microbial community assembly improve our understanding of coastal-sediment carbon cycling and demonstrate the importance of diverse microbiota in processing this abundant pool of organic carbon. 28289404 9 21 theme carbon-loss 1770:1780 arg1 assembly 1835:1842 microbial community assembly 1815:1842 microbial community assembly 1815:1842 These differential effects of EPS fractions on carbon-loss rates, nutrient regeneration and microbial community assembly improve our understanding of coastal-sediment carbon cycling and demonstrate the importance of diverse microbiota in processing this abundant pool of organic carbon. 28289404 0 22 from Changes 75:81 arg1 Communities 110:120 Heterotrophic Bacterial Communities 86:120 Heterotrophic Bacterial Communities from Intertidal Sediments 86:146 Different Types of Diatom-Derived Extracellular Polymeric Substances Drive Changes in Heterotrophic Bacterial Communities from Intertidal Sediments. 28289404 0 22 from Changes 75:81 arg1 Sediments 138:146 Intertidal Sediments 127:146 Intertidal Sediments 127:146 Different Types of Diatom-Derived Extracellular Polymeric Substances Drive Changes in Heterotrophic Bacterial Communities from Intertidal Sediments. 28289404 8 23 dep especially 1569:1578 arg1 Tenacibaculum 1580:1592 Tenacibaculum 1580:1592 Tenacibaculum 1580:1592 Bacteroidetes (especially Tenacibaculum) and Verrucomicrobia increased significantly in relative abundance in both the hot-bicarbonate-EPS and colloidal-EPS treatments. 28289404 1 24 theme Intertidal 149:158 arg1 areas 160:164 Intertidal areas 149:164 Intertidal areas 149:164 Intertidal areas support extensive diatom-rich biofilms. 28289404 8 25 from abundance 1651:1659 arg1 colloidal-EPS 1697:1709 colloidal-EPS 1697:1709 colloidal-EPS 1697:1709 Bacteroidetes (especially Tenacibaculum) and Verrucomicrobia increased significantly in relative abundance in both the hot-bicarbonate-EPS and colloidal-EPS treatments. 28289404 8 25 from abundance 1651:1659 arg1 hot-bicarbonate-EPS 1673:1691 hot-bicarbonate-EPS 1673:1691 hot-bicarbonate-EPS 1673:1691 Bacteroidetes (especially Tenacibaculum) and Verrucomicrobia increased significantly in relative abundance in both the hot-bicarbonate-EPS and colloidal-EPS treatments. 28289404 4 26 dep sources 660:666 arg1 EPS 769:771 the more complex hot-bicarbonate-extracted EPS 726:771 the more complex hot-bicarbonate-extracted EPS 726:771 An aerobic mudflat-sediment slurry experiment was performed in the dark with two different EPS carbon sources from a diatom-dominated biofilm: colloidal EPS (cEPS) and the more complex hot-bicarbonate-extracted EPS. 28289404 4 26 dep sources 660:666 arg1 cEPS 716:719 cEPS 716:719 cEPS 716:719 An aerobic mudflat-sediment slurry experiment was performed in the dark with two different EPS carbon sources from a diatom-dominated biofilm: colloidal EPS (cEPS) and the more complex hot-bicarbonate-extracted EPS. 28289404 4 26 dep sources 660:666 arg1 EPS 711:713 colloidal EPS 701:713 colloidal EPS (cEPS) 701:720 An aerobic mudflat-sediment slurry experiment was performed in the dark with two different EPS carbon sources from a diatom-dominated biofilm: colloidal EPS (cEPS) and the more complex hot-bicarbonate-extracted EPS. 28289404 4 26 dep sources 660:666 arg1 sources 660:666 two different EPS carbon sources 635:666 two different EPS carbon sources from a diatom-dominated biofilm: colloidal EPS (cEPS) and the more complex hot-bicarbonate-extracted EPS 635:771 An aerobic mudflat-sediment slurry experiment was performed in the dark with two different EPS carbon sources from a diatom-dominated biofilm: colloidal EPS (cEPS) and the more complex hot-bicarbonate-extracted EPS. 28289404 7 27 theme rRNA 1383:1386 arg1 genes 1388:1392 bacterial 16S rRNA genes 1369:1392 bacterial 16S rRNA genes 1369:1392 Microbial biomass increased ~4-6-fold over 9 days, and pyrosequencing of bacterial 16S rRNA genes revealed that the addition of both types of EPS greatly altered the bacterial community composition (from 0 to 9 days) compared to a control with no added EPS. 28289404 3 28 theme degradation 427:437 arg1 rates 439:443 degradation rates 427:443 degradation rates of different EPS components 427:471 However, degradation rates of different EPS components, and how they shape heterotrophic communities in sediments, are not well understood. 28289404 1 29 theme diatom-rich 184:194 arg1 biofilms 196:203 extensive diatom-rich biofilms 174:203 extensive diatom-rich biofilms 174:203 Intertidal areas support extensive diatom-rich biofilms. 28289404 9 30 theme microbial 1815:1823 arg1 rates 1782:1786 carbon-loss rates 1770:1786 carbon-loss rates 1770:1786 These differential effects of EPS fractions on carbon-loss rates, nutrient regeneration and microbial community assembly improve our understanding of coastal-sediment carbon cycling and demonstrate the importance of diverse microbiota in processing this abundant pool of organic carbon. 28289404 9 30 theme microbial 1815:1823 arg1 assembly 1835:1842 microbial community assembly 1815:1842 microbial community assembly 1815:1842 These differential effects of EPS fractions on carbon-loss rates, nutrient regeneration and microbial community assembly improve our understanding of coastal-sediment carbon cycling and demonstrate the importance of diverse microbiota in processing this abundant pool of organic carbon. 28289404 8 31 dep hot-bicarbonate-EPS 1673:1691 arg1 treatments 1711:1720 treatments 1711:1720 treatments 1711:1720 Bacteroidetes (especially Tenacibaculum) and Verrucomicrobia increased significantly in relative abundance in both the hot-bicarbonate-EPS and colloidal-EPS treatments. 28289404 8 31 dep hot-bicarbonate-EPS 1673:1691 arg1 the 1669:1671 the 1669:1671 the 1669:1671 Bacteroidetes (especially Tenacibaculum) and Verrucomicrobia increased significantly in relative abundance in both the hot-bicarbonate-EPS and colloidal-EPS treatments. 28289404 4 32 theme complex 735:741 arg1 EPS 769:771 the more complex hot-bicarbonate-extracted EPS 726:771 the more complex hot-bicarbonate-extracted EPS 726:771 An aerobic mudflat-sediment slurry experiment was performed in the dark with two different EPS carbon sources from a diatom-dominated biofilm: colloidal EPS (cEPS) and the more complex hot-bicarbonate-extracted EPS. 28289404 4 32 theme complex 735:741 arg1 sources 660:666 two different EPS carbon sources 635:666 two different EPS carbon sources from a diatom-dominated biofilm: colloidal EPS (cEPS) and the more complex hot-bicarbonate-extracted EPS 635:771 An aerobic mudflat-sediment slurry experiment was performed in the dark with two different EPS carbon sources from a diatom-dominated biofilm: colloidal EPS (cEPS) and the more complex hot-bicarbonate-extracted EPS. 28289404 0 33 theme Heterotrophic 86:98 arg1 Communities 110:120 Heterotrophic Bacterial Communities 86:120 Heterotrophic Bacterial Communities from Intertidal Sediments 86:146 Different Types of Diatom-Derived Extracellular Polymeric Substances Drive Changes in Heterotrophic Bacterial Communities from Intertidal Sediments. 28289404 0 34 theme Intertidal 127:136 arg1 Sediments 138:146 Intertidal Sediments 127:146 Intertidal Sediments 127:146 Different Types of Diatom-Derived Extracellular Polymeric Substances Drive Changes in Heterotrophic Bacterial Communities from Intertidal Sediments. 28289404 5 35 theme sediment 834:841 arg1 fractions 843:851 three sediment fractions [dissolved organic carbon (DOC) 828:883 three sediment fractions [dissolved organic carbon (DOC) 828:883 Degradation rate constants determined over 9 days for three sediment fractions [dissolved organic carbon (DOC), total carbohydrates (TCHO), and (cEPS)] were generally higher in the colloidal-EPS slurries (0.105-0.123 d-1) compared with the hot-bicarbonate-extracted-EPS slurries (0.060-0.096 d-1). 28289404 6 36 theme large 1116:1120 arg1 increases 1122:1130 large increases 1116:1130 large increases in dissolved nitrogen 1116:1152 Addition of hot-bicarbonate-EPS resulted in large increases in dissolved nitrogen and phosphorous by the end of the experiment, indicating that the more complex EPS is an important source of regenerated inorganic nutrients. 28289404 0 37 theme Different 0:8 arg1 Types 10:14 Different Types 0:14 Different Types of Diatom-Derived Extracellular Polymeric Substances 0:67 Different Types of Diatom-Derived Extracellular Polymeric Substances Drive Changes in Heterotrophic Bacterial Communities from Intertidal Sediments. 28289404 2 38 theme substances 293:302 arg1 quantities 255:264 large quantities 249:264 large quantities 249:264 Such microphytobenthic (MPB) diatoms exude large quantities of extracellular polymeric substances (EPS) comprising polysaccharides, glycoproteins and other biopolymers, which represent a substantial carbon pool. 28289404 9 39 dep processing 1961:1970 arg1 pool 1986:1989 this abundant pool 1972:1989 processing this abundant pool of organic carbon 1961:2007 These differential effects of EPS fractions on carbon-loss rates, nutrient regeneration and microbial community assembly improve our understanding of coastal-sediment carbon cycling and demonstrate the importance of diverse microbiota in processing this abundant pool of organic carbon. 28289404 5 40 theme colloidal-EPS 955:967 arg1 slurries 969:976 the colloidal-EPS slurries 951:976 the colloidal-EPS slurries (0.105-0.123 d-1) 951:994 Degradation rate constants determined over 9 days for three sediment fractions [dissolved organic carbon (DOC), total carbohydrates (TCHO), and (cEPS)] were generally higher in the colloidal-EPS slurries (0.105-0.123 d-1) compared with the hot-bicarbonate-extracted-EPS slurries (0.060-0.096 d-1). 28289404 5 40 theme colloidal-EPS 955:967 arg1 d-1 991:993 0.105-0.123 d-1 979:993 0.105-0.123 d-1 979:993 Degradation rate constants determined over 9 days for three sediment fractions [dissolved organic carbon (DOC), total carbohydrates (TCHO), and (cEPS)] were generally higher in the colloidal-EPS slurries (0.105-0.123 d-1) compared with the hot-bicarbonate-extracted-EPS slurries (0.060-0.096 d-1). 28289404 9 41 theme carbon 1890:1895 arg1 cycling 1897:1903 coastal-sediment carbon cycling 1873:1903 coastal-sediment carbon cycling 1873:1903 These differential effects of EPS fractions on carbon-loss rates, nutrient regeneration and microbial community assembly improve our understanding of coastal-sediment carbon cycling and demonstrate the importance of diverse microbiota in processing this abundant pool of organic carbon. 28289404 7 42 theme added 1543:1547 arg1 EPS 1549:1551 no added EPS 1540:1551 no added EPS 1540:1551 Microbial biomass increased ~4-6-fold over 9 days, and pyrosequencing of bacterial 16S rRNA genes revealed that the addition of both types of EPS greatly altered the bacterial community composition (from 0 to 9 days) compared to a control with no added EPS. 28289404 3 43 theme components 462:471 arg1 rates 439:443 degradation rates 427:443 degradation rates of different EPS components 427:471 However, degradation rates of different EPS components, and how they shape heterotrophic communities in sediments, are not well understood. 28289404 3 44 theme heterotrophic 493:505 arg1 communities 507:517 heterotrophic communities 493:517 heterotrophic communities in sediments 493:530 However, degradation rates of different EPS components, and how they shape heterotrophic communities in sediments, are not well understood. 28289404 0 45 theme Extracellular 34:46 arg1 Substances 58:67 Diatom-Derived Extracellular Polymeric Substances 19:67 Diatom-Derived Extracellular Polymeric Substances 19:67 Different Types of Diatom-Derived Extracellular Polymeric Substances Drive Changes in Heterotrophic Bacterial Communities from Intertidal Sediments. 28289404 3 46 theme different 448:456 arg1 components 462:471 different EPS components 448:471 different EPS components 448:471 However, degradation rates of different EPS components, and how they shape heterotrophic communities in sediments, are not well understood. 28289404 4 47 theme mudflat-sediment 569:584 arg1 experiment 593:602 An aerobic mudflat-sediment slurry experiment 558:602 An aerobic mudflat-sediment slurry experiment 558:602 An aerobic mudflat-sediment slurry experiment was performed in the dark with two different EPS carbon sources from a diatom-dominated biofilm: colloidal EPS (cEPS) and the more complex hot-bicarbonate-extracted EPS. 28289404 2 48 theme Such 206:209 arg1 diatoms 235:241 Such microphytobenthic (MPB) diatoms 206:241 Such microphytobenthic (MPB) diatoms 206:241 Such microphytobenthic (MPB) diatoms exude large quantities of extracellular polymeric substances (EPS) comprising polysaccharides, glycoproteins and other biopolymers, which represent a substantial carbon pool. 28289404 3 49 from communities 507:517 arg1 sediments 522:530 sediments 522:530 sediments 522:530 However, degradation rates of different EPS components, and how they shape heterotrophic communities in sediments, are not well understood. 28289404 2 50 theme substantial 393:403 arg1 pool 412:415 a substantial carbon pool 391:415 a substantial carbon pool 391:415 Such microphytobenthic (MPB) diatoms exude large quantities of extracellular polymeric substances (EPS) comprising polysaccharides, glycoproteins and other biopolymers, which represent a substantial carbon pool. 28289404 5 51 theme organic 864:870 arg1 DOC 880:882 DOC 880:882 DOC 880:882 Degradation rate constants determined over 9 days for three sediment fractions [dissolved organic carbon (DOC), total carbohydrates (TCHO), and (cEPS)] were generally higher in the colloidal-EPS slurries (0.105-0.123 d-1) compared with the hot-bicarbonate-extracted-EPS slurries (0.060-0.096 d-1). 28289404 5 51 theme organic 864:870 arg1 carbon 872:877 [dissolved organic carbon 853:877 three sediment fractions [dissolved organic carbon (DOC) 828:883 Degradation rate constants determined over 9 days for three sediment fractions [dissolved organic carbon (DOC), total carbohydrates (TCHO), and (cEPS)] were generally higher in the colloidal-EPS slurries (0.105-0.123 d-1) compared with the hot-bicarbonate-extracted-EPS slurries (0.060-0.096 d-1). 28289404 6 52 theme complex 1225:1231 arg1 source 1253:1258 an important source 1240:1258 an important source of regenerated inorganic nutrients 1240:1293 Addition of hot-bicarbonate-EPS resulted in large increases in dissolved nitrogen and phosphorous by the end of the experiment, indicating that the more complex EPS is an important source of regenerated inorganic nutrients. 28289404 6 52 theme complex 1225:1231 arg1 EPS 1233:1235 the more complex EPS 1216:1235 the more complex EPS 1216:1235 Addition of hot-bicarbonate-EPS resulted in large increases in dissolved nitrogen and phosphorous by the end of the experiment, indicating that the more complex EPS is an important source of regenerated inorganic nutrients. 28289404 9 53 theme microbiota 1947:1956 arg1 importance 1925:1934 the importance 1921:1934 the importance of diverse microbiota in processing this abundant pool of organic carbon 1921:2007 These differential effects of EPS fractions on carbon-loss rates, nutrient regeneration and microbial community assembly improve our understanding of coastal-sediment carbon cycling and demonstrate the importance of diverse microbiota in processing this abundant pool of organic carbon. 28289404 4 54 theme carbon 653:658 arg1 sources 660:666 two different EPS carbon sources 635:666 two different EPS carbon sources from a diatom-dominated biofilm: colloidal EPS (cEPS) and the more complex hot-bicarbonate-extracted EPS 635:771 An aerobic mudflat-sediment slurry experiment was performed in the dark with two different EPS carbon sources from a diatom-dominated biofilm: colloidal EPS (cEPS) and the more complex hot-bicarbonate-extracted EPS. 28289404 4 54 theme carbon 653:658 arg1 EPS 711:713 colloidal EPS 701:713 colloidal EPS (cEPS) 701:720 An aerobic mudflat-sediment slurry experiment was performed in the dark with two different EPS carbon sources from a diatom-dominated biofilm: colloidal EPS (cEPS) and the more complex hot-bicarbonate-extracted EPS. 28289404 4 54 theme carbon 653:658 arg1 EPS 769:771 the more complex hot-bicarbonate-extracted EPS 726:771 the more complex hot-bicarbonate-extracted EPS 726:771 An aerobic mudflat-sediment slurry experiment was performed in the dark with two different EPS carbon sources from a diatom-dominated biofilm: colloidal EPS (cEPS) and the more complex hot-bicarbonate-extracted EPS. 28289404 7 55 theme Microbial 1296:1304 arg1 biomass 1306:1312 Microbial biomass 1296:1312 Microbial biomass 1296:1312 Microbial biomass increased ~4-6-fold over 9 days, and pyrosequencing of bacterial 16S rRNA genes revealed that the addition of both types of EPS greatly altered the bacterial community composition (from 0 to 9 days) compared to a control with no added EPS. 28289404 9 56 theme abundant 1977:1984 arg1 pool 1986:1989 this abundant pool 1972:1989 processing this abundant pool of organic carbon 1961:2007 These differential effects of EPS fractions on carbon-loss rates, nutrient regeneration and microbial community assembly improve our understanding of coastal-sediment carbon cycling and demonstrate the importance of diverse microbiota in processing this abundant pool of organic carbon. 28289404 7 57 theme community 1472:1480 arg1 composition 1482:1492 the bacterial community composition 1458:1492 the bacterial community composition (from 0 to 9 days) 1458:1511 Microbial biomass increased ~4-6-fold over 9 days, and pyrosequencing of bacterial 16S rRNA genes revealed that the addition of both types of EPS greatly altered the bacterial community composition (from 0 to 9 days) compared to a control with no added EPS. 28289404 4 58 theme different 639:647 arg1 sources 660:666 two different EPS carbon sources 635:666 two different EPS carbon sources from a diatom-dominated biofilm: colloidal EPS (cEPS) and the more complex hot-bicarbonate-extracted EPS 635:771 An aerobic mudflat-sediment slurry experiment was performed in the dark with two different EPS carbon sources from a diatom-dominated biofilm: colloidal EPS (cEPS) and the more complex hot-bicarbonate-extracted EPS. 28289404 4 58 theme different 639:647 arg1 EPS 711:713 colloidal EPS 701:713 colloidal EPS (cEPS) 701:720 An aerobic mudflat-sediment slurry experiment was performed in the dark with two different EPS carbon sources from a diatom-dominated biofilm: colloidal EPS (cEPS) and the more complex hot-bicarbonate-extracted EPS. 28289404 4 58 theme different 639:647 arg1 EPS 769:771 the more complex hot-bicarbonate-extracted EPS 726:771 the more complex hot-bicarbonate-extracted EPS 726:771 An aerobic mudflat-sediment slurry experiment was performed in the dark with two different EPS carbon sources from a diatom-dominated biofilm: colloidal EPS (cEPS) and the more complex hot-bicarbonate-extracted EPS. 28289404 0 59 theme Substances 58:67 arg1 Types 10:14 Different Types 0:14 Different Types of Diatom-Derived Extracellular Polymeric Substances 0:67 Different Types of Diatom-Derived Extracellular Polymeric Substances Drive Changes in Heterotrophic Bacterial Communities from Intertidal Sediments. 28289404 9 60 theme carbon 2002:2007 arg1 pool 1986:1989 this abundant pool 1972:1989 processing this abundant pool of organic carbon 1961:2007 These differential effects of EPS fractions on carbon-loss rates, nutrient regeneration and microbial community assembly improve our understanding of coastal-sediment carbon cycling and demonstrate the importance of diverse microbiota in processing this abundant pool of organic carbon. 28289404 6 61 theme nutrients 1285:1293 arg1 source 1253:1258 an important source 1240:1258 an important source of regenerated inorganic nutrients 1240:1293 Addition of hot-bicarbonate-EPS resulted in large increases in dissolved nitrogen and phosphorous by the end of the experiment, indicating that the more complex EPS is an important source of regenerated inorganic nutrients. 28289404 6 61 theme nutrients 1285:1293 arg1 EPS 1233:1235 the more complex EPS 1216:1235 the more complex EPS 1216:1235 Addition of hot-bicarbonate-EPS resulted in large increases in dissolved nitrogen and phosphorous by the end of the experiment, indicating that the more complex EPS is an important source of regenerated inorganic nutrients. 28289404 7 62 with control 1527:1533 arg1 EPS 1549:1551 no added EPS 1540:1551 no added EPS 1540:1551 Microbial biomass increased ~4-6-fold over 9 days, and pyrosequencing of bacterial 16S rRNA genes revealed that the addition of both types of EPS greatly altered the bacterial community composition (from 0 to 9 days) compared to a control with no added EPS. 28289404 5 63 dep fractions 843:851 arg1 DOC 880:882 DOC 880:882 DOC 880:882 Degradation rate constants determined over 9 days for three sediment fractions [dissolved organic carbon (DOC), total carbohydrates (TCHO), and (cEPS)] were generally higher in the colloidal-EPS slurries (0.105-0.123 d-1) compared with the hot-bicarbonate-extracted-EPS slurries (0.060-0.096 d-1). 28289404 5 63 dep fractions 843:851 arg1 carbon 872:877 [dissolved organic carbon 853:877 three sediment fractions [dissolved organic carbon (DOC) 828:883 Degradation rate constants determined over 9 days for three sediment fractions [dissolved organic carbon (DOC), total carbohydrates (TCHO), and (cEPS)] were generally higher in the colloidal-EPS slurries (0.105-0.123 d-1) compared with the hot-bicarbonate-extracted-EPS slurries (0.060-0.096 d-1). 28289404 6 64 theme experiment 1188:1197 arg1 end 1177:1179 the end 1173:1179 the end of the experiment 1173:1197 Addition of hot-bicarbonate-EPS resulted in large increases in dissolved nitrogen and phosphorous by the end of the experiment, indicating that the more complex EPS is an important source of regenerated inorganic nutrients. 28289404 2 65 theme other 356:360 arg1 biopolymers 362:372 other biopolymers 356:372 other biopolymers 356:372 Such microphytobenthic (MPB) diatoms exude large quantities of extracellular polymeric substances (EPS) comprising polysaccharides, glycoproteins and other biopolymers, which represent a substantial carbon pool. 28289404 9 66 theme EPS 1753:1755 arg1 fractions 1757:1765 EPS fractions 1753:1765 EPS fractions 1753:1765 These differential effects of EPS fractions on carbon-loss rates, nutrient regeneration and microbial community assembly improve our understanding of coastal-sediment carbon cycling and demonstrate the importance of diverse microbiota in processing this abundant pool of organic carbon. 28289404 4 67 theme diatom-dominated 675:690 arg1 biofilm 692:698 a diatom-dominated biofilm 673:698 a diatom-dominated biofilm 673:698 An aerobic mudflat-sediment slurry experiment was performed in the dark with two different EPS carbon sources from a diatom-dominated biofilm: colloidal EPS (cEPS) and the more complex hot-bicarbonate-extracted EPS. 28289404 2 68 theme polymeric 283:291 arg1 EPS 305:307 EPS 305:307 EPS 305:307 Such microphytobenthic (MPB) diatoms exude large quantities of extracellular polymeric substances (EPS) comprising polysaccharides, glycoproteins and other biopolymers, which represent a substantial carbon pool. 28289404 2 68 theme polymeric 283:291 arg1 substances 293:302 extracellular polymeric substances 269:302 extracellular polymeric substances (EPS) comprising polysaccharides, glycoproteins and other biopolymers 269:372 Such microphytobenthic (MPB) diatoms exude large quantities of extracellular polymeric substances (EPS) comprising polysaccharides, glycoproteins and other biopolymers, which represent a substantial carbon pool. 28289404 0 69 from Sediments 138:146 arg1 Changes 75:81 Changes 75:81 Changes in Heterotrophic Bacterial Communities from Intertidal Sediments 75:146 Different Types of Diatom-Derived Extracellular Polymeric Substances Drive Changes in Heterotrophic Bacterial Communities from Intertidal Sediments. 28289404 0 69 from Sediments 138:146 arg1 Communities 110:120 Heterotrophic Bacterial Communities 86:120 Heterotrophic Bacterial Communities from Intertidal Sediments 86:146 Different Types of Diatom-Derived Extracellular Polymeric Substances Drive Changes in Heterotrophic Bacterial Communities from Intertidal Sediments. 28289404 6 70 theme important 1243:1251 arg1 source 1253:1258 an important source 1240:1258 an important source of regenerated inorganic nutrients 1240:1293 Addition of hot-bicarbonate-EPS resulted in large increases in dissolved nitrogen and phosphorous by the end of the experiment, indicating that the more complex EPS is an important source of regenerated inorganic nutrients. 28289404 6 70 theme important 1243:1251 arg1 EPS 1233:1235 the more complex EPS 1216:1235 the more complex EPS 1216:1235 Addition of hot-bicarbonate-EPS resulted in large increases in dissolved nitrogen and phosphorous by the end of the experiment, indicating that the more complex EPS is an important source of regenerated inorganic nutrients. 28289404 4 71 theme hot-bicarbonate-extracted 743:767 arg1 EPS 769:771 the more complex hot-bicarbonate-extracted EPS 726:771 the more complex hot-bicarbonate-extracted EPS 726:771 An aerobic mudflat-sediment slurry experiment was performed in the dark with two different EPS carbon sources from a diatom-dominated biofilm: colloidal EPS (cEPS) and the more complex hot-bicarbonate-extracted EPS. 28289404 4 71 theme hot-bicarbonate-extracted 743:767 arg1 sources 660:666 two different EPS carbon sources 635:666 two different EPS carbon sources from a diatom-dominated biofilm: colloidal EPS (cEPS) and the more complex hot-bicarbonate-extracted EPS 635:771 An aerobic mudflat-sediment slurry experiment was performed in the dark with two different EPS carbon sources from a diatom-dominated biofilm: colloidal EPS (cEPS) and the more complex hot-bicarbonate-extracted EPS. 28289404 9 72 theme nutrient 1789:1796 arg1 rates 1782:1786 carbon-loss rates 1770:1786 carbon-loss rates 1770:1786 These differential effects of EPS fractions on carbon-loss rates, nutrient regeneration and microbial community assembly improve our understanding of coastal-sediment carbon cycling and demonstrate the importance of diverse microbiota in processing this abundant pool of organic carbon. 28289404 9 72 theme nutrient 1789:1796 arg1 regeneration 1798:1809 nutrient regeneration 1789:1809 nutrient regeneration 1789:1809 These differential effects of EPS fractions on carbon-loss rates, nutrient regeneration and microbial community assembly improve our understanding of coastal-sediment carbon cycling and demonstrate the importance of diverse microbiota in processing this abundant pool of organic carbon. 28289404 1 73 theme extensive 174:182 arg1 biofilms 196:203 extensive diatom-rich biofilms 174:203 extensive diatom-rich biofilms 174:203 Intertidal areas support extensive diatom-rich biofilms. 28289404 7 74 theme genes 1388:1392 arg1 pyrosequencing 1351:1364 pyrosequencing 1351:1364 pyrosequencing of bacterial 16S rRNA genes 1351:1392 Microbial biomass increased ~4-6-fold over 9 days, and pyrosequencing of bacterial 16S rRNA genes revealed that the addition of both types of EPS greatly altered the bacterial community composition (from 0 to 9 days) compared to a control with no added EPS. 28289404 0 75 theme Bacterial 100:108 arg1 Communities 110:120 Heterotrophic Bacterial Communities 86:120 Heterotrophic Bacterial Communities from Intertidal Sediments 86:146 Different Types of Diatom-Derived Extracellular Polymeric Substances Drive Changes in Heterotrophic Bacterial Communities from Intertidal Sediments. 28289404 9 76 theme community 1825:1833 arg1 rates 1782:1786 carbon-loss rates 1770:1786 carbon-loss rates 1770:1786 These differential effects of EPS fractions on carbon-loss rates, nutrient regeneration and microbial community assembly improve our understanding of coastal-sediment carbon cycling and demonstrate the importance of diverse microbiota in processing this abundant pool of organic carbon. 28289404 9 76 theme community 1825:1833 arg1 assembly 1835:1842 microbial community assembly 1815:1842 microbial community assembly 1815:1842 These differential effects of EPS fractions on carbon-loss rates, nutrient regeneration and microbial community assembly improve our understanding of coastal-sediment carbon cycling and demonstrate the importance of diverse microbiota in processing this abundant pool of organic carbon. 28289404 4 77 theme aerobic 561:567 arg1 experiment 593:602 An aerobic mudflat-sediment slurry experiment 558:602 An aerobic mudflat-sediment slurry experiment 558:602 An aerobic mudflat-sediment slurry experiment was performed in the dark with two different EPS carbon sources from a diatom-dominated biofilm: colloidal EPS (cEPS) and the more complex hot-bicarbonate-extracted EPS. 28289404 5 78 theme rate 786:789 arg1 constants 791:799 Degradation rate constants 774:799 Degradation rate constants determined over 9 days for three sediment fractions [dissolved organic carbon (DOC), total carbohydrates (TCHO), and (cEPS)] 774:924 Degradation rate constants determined over 9 days for three sediment fractions [dissolved organic carbon (DOC), total carbohydrates (TCHO), and (cEPS)] were generally higher in the colloidal-EPS slurries (0.105-0.123 d-1) compared with the hot-bicarbonate-extracted-EPS slurries (0.060-0.096 d-1). 28289404 7 79 theme bacterial 1369:1377 arg1 genes 1388:1392 bacterial 16S rRNA genes 1369:1392 bacterial 16S rRNA genes 1369:1392 Microbial biomass increased ~4-6-fold over 9 days, and pyrosequencing of bacterial 16S rRNA genes revealed that the addition of both types of EPS greatly altered the bacterial community composition (from 0 to 9 days) compared to a control with no added EPS. 28289404 3 80 dep understood 546:555 arg1 shape 487:491 shape 487:491 shape heterotrophic communities in sediments 487:530 However, degradation rates of different EPS components, and how they shape heterotrophic communities in sediments, are not well understood. 28289404 9 81 theme coastal-sediment 1873:1888 arg1 cycling 1897:1903 coastal-sediment carbon cycling 1873:1903 coastal-sediment carbon cycling 1873:1903 These differential effects of EPS fractions on carbon-loss rates, nutrient regeneration and microbial community assembly improve our understanding of coastal-sediment carbon cycling and demonstrate the importance of diverse microbiota in processing this abundant pool of organic carbon. 28289404 0 82 theme Diatom-Derived 19:32 arg1 Substances 58:67 Diatom-Derived Extracellular Polymeric Substances 19:67 Diatom-Derived Extracellular Polymeric Substances 19:67 Different Types of Diatom-Derived Extracellular Polymeric Substances Drive Changes in Heterotrophic Bacterial Communities from Intertidal Sediments. 28289404 7 83 dep 9 1505:1505 arg1 to 1502:1503 to 1502:1503 to 1502:1503 Microbial biomass increased ~4-6-fold over 9 days, and pyrosequencing of bacterial 16S rRNA genes revealed that the addition of both types of EPS greatly altered the bacterial community composition (from 0 to 9 days) compared to a control with no added EPS. 28289404 6 84 theme hot-bicarbonate-EPS 1084:1102 arg1 Addition 1072:1079 Addition 1072:1079 Addition of hot-bicarbonate-EPS 1072:1102 Addition of hot-bicarbonate-EPS resulted in large increases in dissolved nitrogen and phosphorous by the end of the experiment, indicating that the more complex EPS is an important source of regenerated inorganic nutrients. 28289404 9 85 theme cycling 1897:1903 arg1 understanding 1856:1868 our understanding 1852:1868 our understanding of coastal-sediment carbon cycling 1852:1903 These differential effects of EPS fractions on carbon-loss rates, nutrient regeneration and microbial community assembly improve our understanding of coastal-sediment carbon cycling and demonstrate the importance of diverse microbiota in processing this abundant pool of organic carbon. 28289404 2 86 theme MPB 230:232 arg1 diatoms 235:241 Such microphytobenthic (MPB) diatoms 206:241 Such microphytobenthic (MPB) diatoms 206:241 Such microphytobenthic (MPB) diatoms exude large quantities of extracellular polymeric substances (EPS) comprising polysaccharides, glycoproteins and other biopolymers, which represent a substantial carbon pool. 28289404 0 87 theme Polymeric 48:56 arg1 Substances 58:67 Diatom-Derived Extracellular Polymeric Substances 19:67 Diatom-Derived Extracellular Polymeric Substances 19:67 Different Types of Diatom-Derived Extracellular Polymeric Substances Drive Changes in Heterotrophic Bacterial Communities from Intertidal Sediments. 28289404 4 88 theme slurry 586:591 arg1 experiment 593:602 An aerobic mudflat-sediment slurry experiment 558:602 An aerobic mudflat-sediment slurry experiment 558:602 An aerobic mudflat-sediment slurry experiment was performed in the dark with two different EPS carbon sources from a diatom-dominated biofilm: colloidal EPS (cEPS) and the more complex hot-bicarbonate-extracted EPS. 28289404 2 89 theme microphytobenthic 211:227 arg1 diatoms 235:241 Such microphytobenthic (MPB) diatoms 206:241 Such microphytobenthic (MPB) diatoms 206:241 Such microphytobenthic (MPB) diatoms exude large quantities of extracellular polymeric substances (EPS) comprising polysaccharides, glycoproteins and other biopolymers, which represent a substantial carbon pool. 28289404 5 90 theme [dissolved 853:862 arg1 DOC 880:882 DOC 880:882 DOC 880:882 Degradation rate constants determined over 9 days for three sediment fractions [dissolved organic carbon (DOC), total carbohydrates (TCHO), and (cEPS)] were generally higher in the colloidal-EPS slurries (0.105-0.123 d-1) compared with the hot-bicarbonate-extracted-EPS slurries (0.060-0.096 d-1). 28289404 5 90 theme [dissolved 853:862 arg1 carbon 872:877 [dissolved organic carbon 853:877 three sediment fractions [dissolved organic carbon (DOC) 828:883 Degradation rate constants determined over 9 days for three sediment fractions [dissolved organic carbon (DOC), total carbohydrates (TCHO), and (cEPS)] were generally higher in the colloidal-EPS slurries (0.105-0.123 d-1) compared with the hot-bicarbonate-extracted-EPS slurries (0.060-0.096 d-1). 28289404 3 91 theme EPS 458:460 arg1 components 462:471 different EPS components 448:471 different EPS components 448:471 However, degradation rates of different EPS components, and how they shape heterotrophic communities in sediments, are not well understood. 28289404 2 92 theme large 249:253 arg1 quantities 255:264 large quantities 249:264 large quantities 249:264 Such microphytobenthic (MPB) diatoms exude large quantities of extracellular polymeric substances (EPS) comprising polysaccharides, glycoproteins and other biopolymers, which represent a substantial carbon pool. 28289404 9 93 theme diverse 1939:1945 arg1 microbiota 1947:1956 diverse microbiota 1939:1956 diverse microbiota 1939:1956 These differential effects of EPS fractions on carbon-loss rates, nutrient regeneration and microbial community assembly improve our understanding of coastal-sediment carbon cycling and demonstrate the importance of diverse microbiota in processing this abundant pool of organic carbon. 28289404 5 94 theme hot-bicarbonate-extracted-EPS 1014:1042 arg1 slurries 1044:1051 the hot-bicarbonate-extracted-EPS slurries 1010:1051 the hot-bicarbonate-extracted-EPS slurries (0.060-0.096 d-1) 1010:1069 Degradation rate constants determined over 9 days for three sediment fractions [dissolved organic carbon (DOC), total carbohydrates (TCHO), and (cEPS)] were generally higher in the colloidal-EPS slurries (0.105-0.123 d-1) compared with the hot-bicarbonate-extracted-EPS slurries (0.060-0.096 d-1). 28289404 5 94 theme hot-bicarbonate-extracted-EPS 1014:1042 arg1 d-1 1066:1068 0.060-0.096 d-1 1054:1068 0.060-0.096 d-1 1054:1068 Degradation rate constants determined over 9 days for three sediment fractions [dissolved organic carbon (DOC), total carbohydrates (TCHO), and (cEPS)] were generally higher in the colloidal-EPS slurries (0.105-0.123 d-1) compared with the hot-bicarbonate-extracted-EPS slurries (0.060-0.096 d-1). 28289404 7 95 theme 16S 1379:1381 arg1 genes 1388:1392 bacterial 16S rRNA genes 1369:1392 bacterial 16S rRNA genes 1369:1392 Microbial biomass increased ~4-6-fold over 9 days, and pyrosequencing of bacterial 16S rRNA genes revealed that the addition of both types of EPS greatly altered the bacterial community composition (from 0 to 9 days) compared to a control with no added EPS. 28289404 8 96 theme relative 1642:1649 arg1 abundance 1651:1659 relative abundance 1642:1659 relative abundance in both the hot-bicarbonate-EPS and colloidal-EPS treatments 1642:1720 Bacteroidetes (especially Tenacibaculum) and Verrucomicrobia increased significantly in relative abundance in both the hot-bicarbonate-EPS and colloidal-EPS treatments. 27458233 5 0 theme psm 867:869 arg1 genes 871:875 the psm genes 863:875 the psm genes 863:875 Here, we show that subinhibitory concentrations of clindamycin triggered a transcriptional stress response in S. aureus via the alternative sigma factor B (σ(B)) and upregulated the expression of the major biofilm-associated genes atlA, lrgA, agrA, the psm genes, fnbA, and fnbB Our data suggest that subinhibitory concentrations of clindamycin alter the ability of S. aureus to form biofilms and shift the composition of the biofilm matrix toward higher eDNA content. 27458233 6 1 theme antibiotic 1301:1310 arg1 strategies 1322:1331 antibiotic treatment strategies 1301:1331 antibiotic treatment strategies of biofilm-associated S. aureus infections 1301:1374 An understanding of the molecular mechanisms underlying biofilm assembly and dispersal in response to subinhibitory concentrations of clinically relevant antibiotics such as clindamycin is critical to further optimize antibiotic treatment strategies of biofilm-associated S. aureus infections. 27458233 6 2 theme molecular 1107:1115 arg1 mechanisms 1117:1126 the molecular mechanisms 1103:1126 the molecular mechanisms underlying biofilm assembly and dispersal in response to subinhibitory concentrations of clinically relevant antibiotics such as clindamycin 1103:1267 An understanding of the molecular mechanisms underlying biofilm assembly and dispersal in response to subinhibitory concentrations of clinically relevant antibiotics such as clindamycin is critical to further optimize antibiotic treatment strategies of biofilm-associated S. aureus infections. 27458233 0 3 theme Clindamycin 86:96 arg1 Concentrations 68:81 Subinhibitory Concentrations 54:81 Subinhibitory Concentrations of Clindamycin 54:96 Modulation of Staphylococcus aureus Biofilm Matrix by Subinhibitory Concentrations of Clindamycin. 27458233 5 4 theme clindamycin 665:675 arg1 concentrations 647:660 subinhibitory concentrations 633:660 subinhibitory concentrations of clindamycin 633:675 Here, we show that subinhibitory concentrations of clindamycin triggered a transcriptional stress response in S. aureus via the alternative sigma factor B (σ(B)) and upregulated the expression of the major biofilm-associated genes atlA, lrgA, agrA, the psm genes, fnbA, and fnbB Our data suggest that subinhibitory concentrations of clindamycin alter the ability of S. aureus to form biofilms and shift the composition of the biofilm matrix toward higher eDNA content. 27458233 6 5 dep concentrations 1199:1212 arg1 response 1173:1180 response 1173:1180 response 1173:1180 An understanding of the molecular mechanisms underlying biofilm assembly and dispersal in response to subinhibitory concentrations of clinically relevant antibiotics such as clindamycin is critical to further optimize antibiotic treatment strategies of biofilm-associated S. aureus infections. 27458233 4 6 theme subinhibitory 569:581 arg1 concentrations 583:596 subinhibitory concentrations 569:596 subinhibitory concentrations of antibiotics 569:611 Many antibiotics do not readily penetrate biofilms, resulting in the presence of subinhibitory concentrations of antibiotics. 27458233 5 7 theme alternative 742:752 arg1 B 767:767 the alternative sigma factor B 738:767 the alternative sigma factor B (σ(B)) 738:774 Here, we show that subinhibitory concentrations of clindamycin triggered a transcriptional stress response in S. aureus via the alternative sigma factor B (σ(B)) and upregulated the expression of the major biofilm-associated genes atlA, lrgA, agrA, the psm genes, fnbA, and fnbB Our data suggest that subinhibitory concentrations of clindamycin alter the ability of S. aureus to form biofilms and shift the composition of the biofilm matrix toward higher eDNA content. 27458233 6 8 theme subinhibitory 1185:1197 arg1 concentrations 1199:1212 subinhibitory concentrations 1185:1212 subinhibitory concentrations of clinically relevant antibiotics such as clindamycin 1185:1267 An understanding of the molecular mechanisms underlying biofilm assembly and dispersal in response to subinhibitory concentrations of clinically relevant antibiotics such as clindamycin is critical to further optimize antibiotic treatment strategies of biofilm-associated S. aureus infections. 27458233 3 9 theme matrix 411:416 arg1 formation 371:379 the formation 367:379 the formation of an extracellular polymeric matrix, composed of polysaccharides, extracellular DNA (eDNA), and proteins 367:485 Bacteria within a biofilm are shielded from the immune system by the formation of an extracellular polymeric matrix, composed of polysaccharides, extracellular DNA (eDNA), and proteins. 27458233 5 10 theme sigma 754:758 arg1 B 767:767 the alternative sigma factor B 738:767 the alternative sigma factor B (σ(B)) 738:774 Here, we show that subinhibitory concentrations of clindamycin triggered a transcriptional stress response in S. aureus via the alternative sigma factor B (σ(B)) and upregulated the expression of the major biofilm-associated genes atlA, lrgA, agrA, the psm genes, fnbA, and fnbB Our data suggest that subinhibitory concentrations of clindamycin alter the ability of S. aureus to form biofilms and shift the composition of the biofilm matrix toward higher eDNA content. 27458233 5 11 theme biofilm 1040:1046 arg1 matrix 1048:1053 the biofilm matrix 1036:1053 the biofilm matrix 1036:1053 Here, we show that subinhibitory concentrations of clindamycin triggered a transcriptional stress response in S. aureus via the alternative sigma factor B (σ(B)) and upregulated the expression of the major biofilm-associated genes atlA, lrgA, agrA, the psm genes, fnbA, and fnbB Our data suggest that subinhibitory concentrations of clindamycin alter the ability of S. aureus to form biofilms and shift the composition of the biofilm matrix toward higher eDNA content. 27458233 5 12 dep expression 796:805 arg1 suggest 902:908 suggest 902:908 suggest that subinhibitory concentrations of clindamycin alter the ability of S. aureus to form biofilms and shift the composition of the biofilm matrix toward higher eDNA content 902:1080 Here, we show that subinhibitory concentrations of clindamycin triggered a transcriptional stress response in S. aureus via the alternative sigma factor B (σ(B)) and upregulated the expression of the major biofilm-associated genes atlA, lrgA, agrA, the psm genes, fnbA, and fnbB Our data suggest that subinhibitory concentrations of clindamycin alter the ability of S. aureus to form biofilms and shift the composition of the biofilm matrix toward higher eDNA content. 27458233 5 13 theme subinhibitory 915:927 arg1 concentrations 929:942 subinhibitory concentrations 915:942 subinhibitory concentrations of clindamycin 915:957 Here, we show that subinhibitory concentrations of clindamycin triggered a transcriptional stress response in S. aureus via the alternative sigma factor B (σ(B)) and upregulated the expression of the major biofilm-associated genes atlA, lrgA, agrA, the psm genes, fnbA, and fnbB Our data suggest that subinhibitory concentrations of clindamycin alter the ability of S. aureus to form biofilms and shift the composition of the biofilm matrix toward higher eDNA content. 27458233 5 14 theme factor 760:765 arg1 B 767:767 the alternative sigma factor B 738:767 the alternative sigma factor B (σ(B)) 738:774 Here, we show that subinhibitory concentrations of clindamycin triggered a transcriptional stress response in S. aureus via the alternative sigma factor B (σ(B)) and upregulated the expression of the major biofilm-associated genes atlA, lrgA, agrA, the psm genes, fnbA, and fnbB Our data suggest that subinhibitory concentrations of clindamycin alter the ability of S. aureus to form biofilms and shift the composition of the biofilm matrix toward higher eDNA content. 27458233 5 15 theme matrix 1048:1053 arg1 composition 1021:1031 the composition 1017:1031 the composition of the biofilm matrix toward higher eDNA content 1017:1080 Here, we show that subinhibitory concentrations of clindamycin triggered a transcriptional stress response in S. aureus via the alternative sigma factor B (σ(B)) and upregulated the expression of the major biofilm-associated genes atlA, lrgA, agrA, the psm genes, fnbA, and fnbB Our data suggest that subinhibitory concentrations of clindamycin alter the ability of S. aureus to form biofilms and shift the composition of the biofilm matrix toward higher eDNA content. 27458233 3 16 theme extracellular 448:460 arg1 eDNA 467:470 eDNA 467:470 eDNA 467:470 Bacteria within a biofilm are shielded from the immune system by the formation of an extracellular polymeric matrix, composed of polysaccharides, extracellular DNA (eDNA), and proteins. 27458233 3 16 theme extracellular 448:460 arg1 DNA 462:464 extracellular DNA 448:464 extracellular DNA (eDNA) 448:471 Bacteria within a biofilm are shielded from the immune system by the formation of an extracellular polymeric matrix, composed of polysaccharides, extracellular DNA (eDNA), and proteins. 27458233 4 17 theme Many 488:491 arg1 antibiotics 493:503 Many antibiotics 488:503 Many antibiotics 488:503 Many antibiotics do not readily penetrate biofilms, resulting in the presence of subinhibitory concentrations of antibiotics. 27458233 6 18 theme antibiotics 1237:1247 arg1 concentrations 1199:1212 subinhibitory concentrations 1185:1212 subinhibitory concentrations of clinically relevant antibiotics such as clindamycin 1185:1267 An understanding of the molecular mechanisms underlying biofilm assembly and dispersal in response to subinhibitory concentrations of clinically relevant antibiotics such as clindamycin is critical to further optimize antibiotic treatment strategies of biofilm-associated S. aureus infections. 27458233 2 19 theme antibiotic 280:289 arg1 treatment 291:299 antibiotic treatment 280:299 host defenses as well as antibiotic treatment 255:299 They provide a protected niche for the bacteria, rendering them highly recalcitrant toward host defenses as well as antibiotic treatment. 27458233 6 20 theme aureus 1358:1363 arg1 infections 1365:1374 biofilm-associated S. aureus infections 1336:1374 biofilm-associated S. aureus infections 1336:1374 An understanding of the molecular mechanisms underlying biofilm assembly and dispersal in response to subinhibitory concentrations of clinically relevant antibiotics such as clindamycin is critical to further optimize antibiotic treatment strategies of biofilm-associated S. aureus infections. 27458233 3 21 theme extracellular 387:399 arg1 matrix 411:416 an extracellular polymeric matrix 384:416 an extracellular polymeric matrix 384:416 Bacteria within a biofilm are shielded from the immune system by the formation of an extracellular polymeric matrix, composed of polysaccharides, extracellular DNA (eDNA), and proteins. 27458233 5 22 theme higher 1062:1067 arg1 content 1074:1080 higher eDNA content 1062:1080 higher eDNA content 1062:1080 Here, we show that subinhibitory concentrations of clindamycin triggered a transcriptional stress response in S. aureus via the alternative sigma factor B (σ(B)) and upregulated the expression of the major biofilm-associated genes atlA, lrgA, agrA, the psm genes, fnbA, and fnbB Our data suggest that subinhibitory concentrations of clindamycin alter the ability of S. aureus to form biofilms and shift the composition of the biofilm matrix toward higher eDNA content. 27458233 5 23 theme subinhibitory 633:645 arg1 concentrations 647:660 subinhibitory concentrations 633:660 subinhibitory concentrations of clindamycin 633:675 Here, we show that subinhibitory concentrations of clindamycin triggered a transcriptional stress response in S. aureus via the alternative sigma factor B (σ(B)) and upregulated the expression of the major biofilm-associated genes atlA, lrgA, agrA, the psm genes, fnbA, and fnbB Our data suggest that subinhibitory concentrations of clindamycin alter the ability of S. aureus to form biofilms and shift the composition of the biofilm matrix toward higher eDNA content. 27458233 1 24 theme Staphylococcus 99:112 arg1 biofilms 121:128 Staphylococcus aureus biofilms 99:128 Staphylococcus aureus biofilms 99:128 Staphylococcus aureus biofilms are extremely difficult to treat. 27458233 5 25 dep B 767:767 arg1 σ 770:770 σ 770:770 σ(B) 770:773 Here, we show that subinhibitory concentrations of clindamycin triggered a transcriptional stress response in S. aureus via the alternative sigma factor B (σ(B)) and upregulated the expression of the major biofilm-associated genes atlA, lrgA, agrA, the psm genes, fnbA, and fnbB Our data suggest that subinhibitory concentrations of clindamycin alter the ability of S. aureus to form biofilms and shift the composition of the biofilm matrix toward higher eDNA content. 27458233 5 25 dep B 767:767 arg1 B 772:772 B 772:772 B 772:772 Here, we show that subinhibitory concentrations of clindamycin triggered a transcriptional stress response in S. aureus via the alternative sigma factor B (σ(B)) and upregulated the expression of the major biofilm-associated genes atlA, lrgA, agrA, the psm genes, fnbA, and fnbB Our data suggest that subinhibitory concentrations of clindamycin alter the ability of S. aureus to form biofilms and shift the composition of the biofilm matrix toward higher eDNA content. 27458233 3 26 theme polymeric 401:409 arg1 matrix 411:416 an extracellular polymeric matrix 384:416 an extracellular polymeric matrix 384:416 Bacteria within a biofilm are shielded from the immune system by the formation of an extracellular polymeric matrix, composed of polysaccharides, extracellular DNA (eDNA), and proteins. 27458233 1 27 theme aureus 114:119 arg1 biofilms 121:128 Staphylococcus aureus biofilms 99:128 Staphylococcus aureus biofilms 99:128 Staphylococcus aureus biofilms are extremely difficult to treat. 27458233 0 28 theme aureus 29:34 arg1 Matrix 44:49 Staphylococcus aureus Biofilm Matrix 14:49 Staphylococcus aureus Biofilm Matrix 14:49 Modulation of Staphylococcus aureus Biofilm Matrix by Subinhibitory Concentrations of Clindamycin. 27458233 6 29 theme biofilm-associated 1336:1353 arg1 infections 1365:1374 biofilm-associated S. aureus infections 1336:1374 biofilm-associated S. aureus infections 1336:1374 An understanding of the molecular mechanisms underlying biofilm assembly and dispersal in response to subinhibitory concentrations of clinically relevant antibiotics such as clindamycin is critical to further optimize antibiotic treatment strategies of biofilm-associated S. aureus infections. 27458233 5 30 theme major 814:818 arg1 fnbA 878:881 fnbA 878:881 fnbA 878:881 Here, we show that subinhibitory concentrations of clindamycin triggered a transcriptional stress response in S. aureus via the alternative sigma factor B (σ(B)) and upregulated the expression of the major biofilm-associated genes atlA, lrgA, agrA, the psm genes, fnbA, and fnbB Our data suggest that subinhibitory concentrations of clindamycin alter the ability of S. aureus to form biofilms and shift the composition of the biofilm matrix toward higher eDNA content. 27458233 5 30 theme major 814:818 arg1 genes 839:843 the major biofilm-associated genes atlA, lrgA, agrA, the psm genes, fnbA, and fnbB 810:891 the major biofilm-associated genes atlA, lrgA, agrA, the psm genes, fnbA, and fnbB 810:891 Here, we show that subinhibitory concentrations of clindamycin triggered a transcriptional stress response in S. aureus via the alternative sigma factor B (σ(B)) and upregulated the expression of the major biofilm-associated genes atlA, lrgA, agrA, the psm genes, fnbA, and fnbB Our data suggest that subinhibitory concentrations of clindamycin alter the ability of S. aureus to form biofilms and shift the composition of the biofilm matrix toward higher eDNA content. 27458233 5 30 theme major 814:818 arg1 atlA 845:848 atlA 845:848 atlA 845:848 Here, we show that subinhibitory concentrations of clindamycin triggered a transcriptional stress response in S. aureus via the alternative sigma factor B (σ(B)) and upregulated the expression of the major biofilm-associated genes atlA, lrgA, agrA, the psm genes, fnbA, and fnbB Our data suggest that subinhibitory concentrations of clindamycin alter the ability of S. aureus to form biofilms and shift the composition of the biofilm matrix toward higher eDNA content. 27458233 5 30 theme major 814:818 arg1 fnbB 888:891 fnbB 888:891 fnbB 888:891 Here, we show that subinhibitory concentrations of clindamycin triggered a transcriptional stress response in S. aureus via the alternative sigma factor B (σ(B)) and upregulated the expression of the major biofilm-associated genes atlA, lrgA, agrA, the psm genes, fnbA, and fnbB Our data suggest that subinhibitory concentrations of clindamycin alter the ability of S. aureus to form biofilms and shift the composition of the biofilm matrix toward higher eDNA content. 27458233 5 30 theme major 814:818 arg1 lrgA 851:854 lrgA 851:854 lrgA 851:854 Here, we show that subinhibitory concentrations of clindamycin triggered a transcriptional stress response in S. aureus via the alternative sigma factor B (σ(B)) and upregulated the expression of the major biofilm-associated genes atlA, lrgA, agrA, the psm genes, fnbA, and fnbB Our data suggest that subinhibitory concentrations of clindamycin alter the ability of S. aureus to form biofilms and shift the composition of the biofilm matrix toward higher eDNA content. 27458233 5 30 theme major 814:818 arg1 agrA 857:860 agrA 857:860 agrA 857:860 Here, we show that subinhibitory concentrations of clindamycin triggered a transcriptional stress response in S. aureus via the alternative sigma factor B (σ(B)) and upregulated the expression of the major biofilm-associated genes atlA, lrgA, agrA, the psm genes, fnbA, and fnbB Our data suggest that subinhibitory concentrations of clindamycin alter the ability of S. aureus to form biofilms and shift the composition of the biofilm matrix toward higher eDNA content. 27458233 0 31 theme Staphylococcus 14:27 arg1 Matrix 44:49 Staphylococcus aureus Biofilm Matrix 14:49 Staphylococcus aureus Biofilm Matrix 14:49 Modulation of Staphylococcus aureus Biofilm Matrix by Subinhibitory Concentrations of Clindamycin. 27458233 5 32 theme biofilm-associated 820:837 arg1 fnbA 878:881 fnbA 878:881 fnbA 878:881 Here, we show that subinhibitory concentrations of clindamycin triggered a transcriptional stress response in S. aureus via the alternative sigma factor B (σ(B)) and upregulated the expression of the major biofilm-associated genes atlA, lrgA, agrA, the psm genes, fnbA, and fnbB Our data suggest that subinhibitory concentrations of clindamycin alter the ability of S. aureus to form biofilms and shift the composition of the biofilm matrix toward higher eDNA content. 27458233 5 32 theme biofilm-associated 820:837 arg1 genes 839:843 the major biofilm-associated genes atlA, lrgA, agrA, the psm genes, fnbA, and fnbB 810:891 the major biofilm-associated genes atlA, lrgA, agrA, the psm genes, fnbA, and fnbB 810:891 Here, we show that subinhibitory concentrations of clindamycin triggered a transcriptional stress response in S. aureus via the alternative sigma factor B (σ(B)) and upregulated the expression of the major biofilm-associated genes atlA, lrgA, agrA, the psm genes, fnbA, and fnbB Our data suggest that subinhibitory concentrations of clindamycin alter the ability of S. aureus to form biofilms and shift the composition of the biofilm matrix toward higher eDNA content. 27458233 5 32 theme biofilm-associated 820:837 arg1 atlA 845:848 atlA 845:848 atlA 845:848 Here, we show that subinhibitory concentrations of clindamycin triggered a transcriptional stress response in S. aureus via the alternative sigma factor B (σ(B)) and upregulated the expression of the major biofilm-associated genes atlA, lrgA, agrA, the psm genes, fnbA, and fnbB Our data suggest that subinhibitory concentrations of clindamycin alter the ability of S. aureus to form biofilms and shift the composition of the biofilm matrix toward higher eDNA content. 27458233 5 32 theme biofilm-associated 820:837 arg1 fnbB 888:891 fnbB 888:891 fnbB 888:891 Here, we show that subinhibitory concentrations of clindamycin triggered a transcriptional stress response in S. aureus via the alternative sigma factor B (σ(B)) and upregulated the expression of the major biofilm-associated genes atlA, lrgA, agrA, the psm genes, fnbA, and fnbB Our data suggest that subinhibitory concentrations of clindamycin alter the ability of S. aureus to form biofilms and shift the composition of the biofilm matrix toward higher eDNA content. 27458233 5 32 theme biofilm-associated 820:837 arg1 lrgA 851:854 lrgA 851:854 lrgA 851:854 Here, we show that subinhibitory concentrations of clindamycin triggered a transcriptional stress response in S. aureus via the alternative sigma factor B (σ(B)) and upregulated the expression of the major biofilm-associated genes atlA, lrgA, agrA, the psm genes, fnbA, and fnbB Our data suggest that subinhibitory concentrations of clindamycin alter the ability of S. aureus to form biofilms and shift the composition of the biofilm matrix toward higher eDNA content. 27458233 5 32 theme biofilm-associated 820:837 arg1 agrA 857:860 agrA 857:860 agrA 857:860 Here, we show that subinhibitory concentrations of clindamycin triggered a transcriptional stress response in S. aureus via the alternative sigma factor B (σ(B)) and upregulated the expression of the major biofilm-associated genes atlA, lrgA, agrA, the psm genes, fnbA, and fnbB Our data suggest that subinhibitory concentrations of clindamycin alter the ability of S. aureus to form biofilms and shift the composition of the biofilm matrix toward higher eDNA content. 27458233 0 33 theme Matrix 44:49 arg1 Modulation 0:9 Modulation 0:9 Modulation of Staphylococcus aureus Biofilm Matrix by Subinhibitory Concentrations of Clindamycin. 0:97 Modulation of Staphylococcus aureus Biofilm Matrix by Subinhibitory Concentrations of Clindamycin. 27458233 2 34 theme host 255:258 arg1 defenses 260:267 host defenses 255:267 host defenses as well as antibiotic treatment 255:299 They provide a protected niche for the bacteria, rendering them highly recalcitrant toward host defenses as well as antibiotic treatment. 27458233 5 35 theme genes 839:843 arg1 expression 796:805 the expression 792:805 the expression of the major biofilm-associated genes atlA, lrgA, agrA, the psm genes, fnbA, and fnbB Our data suggest that subinhibitory concentrations of clindamycin alter the ability of S. aureus to form biofilms and shift the composition of the biofilm matrix toward higher eDNA content 792:1080 Here, we show that subinhibitory concentrations of clindamycin triggered a transcriptional stress response in S. aureus via the alternative sigma factor B (σ(B)) and upregulated the expression of the major biofilm-associated genes atlA, lrgA, agrA, the psm genes, fnbA, and fnbB Our data suggest that subinhibitory concentrations of clindamycin alter the ability of S. aureus to form biofilms and shift the composition of the biofilm matrix toward higher eDNA content. 27458233 0 36 theme Biofilm 36:42 arg1 Matrix 44:49 Staphylococcus aureus Biofilm Matrix 14:49 Staphylococcus aureus Biofilm Matrix 14:49 Modulation of Staphylococcus aureus Biofilm Matrix by Subinhibitory Concentrations of Clindamycin. 27458233 6 37 theme treatment 1312:1320 arg1 strategies 1322:1331 antibiotic treatment strategies 1301:1331 antibiotic treatment strategies of biofilm-associated S. aureus infections 1301:1374 An understanding of the molecular mechanisms underlying biofilm assembly and dispersal in response to subinhibitory concentrations of clinically relevant antibiotics such as clindamycin is critical to further optimize antibiotic treatment strategies of biofilm-associated S. aureus infections. 27458233 4 38 dep concentrations 583:596 arg1 the 553:555 the 553:555 the 553:555 Many antibiotics do not readily penetrate biofilms, resulting in the presence of subinhibitory concentrations of antibiotics. 27458233 4 38 dep concentrations 583:596 arg1 presence 557:564 presence 557:564 presence 557:564 Many antibiotics do not readily penetrate biofilms, resulting in the presence of subinhibitory concentrations of antibiotics. 27458233 0 39 theme Subinhibitory 54:66 arg1 Concentrations 68:81 Subinhibitory Concentrations 54:81 Subinhibitory Concentrations of Clindamycin 54:96 Modulation of Staphylococcus aureus Biofilm Matrix by Subinhibitory Concentrations of Clindamycin. 27458233 5 40 theme transcriptional 689:703 arg1 response 712:719 a transcriptional stress response 687:719 a transcriptional stress response 687:719 Here, we show that subinhibitory concentrations of clindamycin triggered a transcriptional stress response in S. aureus via the alternative sigma factor B (σ(B)) and upregulated the expression of the major biofilm-associated genes atlA, lrgA, agrA, the psm genes, fnbA, and fnbB Our data suggest that subinhibitory concentrations of clindamycin alter the ability of S. aureus to form biofilms and shift the composition of the biofilm matrix toward higher eDNA content. 27458233 2 41 theme protected 179:187 arg1 niche 189:193 a protected niche 177:193 a protected niche for the bacteria 177:210 They provide a protected niche for the bacteria, rendering them highly recalcitrant toward host defenses as well as antibiotic treatment. 27458233 5 42 theme aureus 983:988 arg1 ability 969:975 the ability 965:975 the ability of S. aureus to form biofilms and shift the composition of the biofilm matrix toward higher eDNA content 965:1080 Here, we show that subinhibitory concentrations of clindamycin triggered a transcriptional stress response in S. aureus via the alternative sigma factor B (σ(B)) and upregulated the expression of the major biofilm-associated genes atlA, lrgA, agrA, the psm genes, fnbA, and fnbB Our data suggest that subinhibitory concentrations of clindamycin alter the ability of S. aureus to form biofilms and shift the composition of the biofilm matrix toward higher eDNA content. 27458233 6 43 theme biofilm 1139:1145 arg1 assembly 1147:1154 biofilm assembly 1139:1154 biofilm assembly 1139:1154 An understanding of the molecular mechanisms underlying biofilm assembly and dispersal in response to subinhibitory concentrations of clinically relevant antibiotics such as clindamycin is critical to further optimize antibiotic treatment strategies of biofilm-associated S. aureus infections. 27458233 5 44 theme stress 705:710 arg1 response 712:719 a transcriptional stress response 687:719 a transcriptional stress response 687:719 Here, we show that subinhibitory concentrations of clindamycin triggered a transcriptional stress response in S. aureus via the alternative sigma factor B (σ(B)) and upregulated the expression of the major biofilm-associated genes atlA, lrgA, agrA, the psm genes, fnbA, and fnbB Our data suggest that subinhibitory concentrations of clindamycin alter the ability of S. aureus to form biofilms and shift the composition of the biofilm matrix toward higher eDNA content. 27458233 4 45 theme antibiotics 601:611 arg1 concentrations 583:596 subinhibitory concentrations 569:596 subinhibitory concentrations of antibiotics 569:611 Many antibiotics do not readily penetrate biofilms, resulting in the presence of subinhibitory concentrations of antibiotics. 27458233 5 46 dep genes 839:843 arg1 fnbA 878:881 fnbA 878:881 fnbA 878:881 Here, we show that subinhibitory concentrations of clindamycin triggered a transcriptional stress response in S. aureus via the alternative sigma factor B (σ(B)) and upregulated the expression of the major biofilm-associated genes atlA, lrgA, agrA, the psm genes, fnbA, and fnbB Our data suggest that subinhibitory concentrations of clindamycin alter the ability of S. aureus to form biofilms and shift the composition of the biofilm matrix toward higher eDNA content. 27458233 5 46 dep genes 839:843 arg1 genes 839:843 the major biofilm-associated genes atlA, lrgA, agrA, the psm genes, fnbA, and fnbB 810:891 the major biofilm-associated genes atlA, lrgA, agrA, the psm genes, fnbA, and fnbB 810:891 Here, we show that subinhibitory concentrations of clindamycin triggered a transcriptional stress response in S. aureus via the alternative sigma factor B (σ(B)) and upregulated the expression of the major biofilm-associated genes atlA, lrgA, agrA, the psm genes, fnbA, and fnbB Our data suggest that subinhibitory concentrations of clindamycin alter the ability of S. aureus to form biofilms and shift the composition of the biofilm matrix toward higher eDNA content. 27458233 5 46 dep genes 839:843 arg1 atlA 845:848 atlA 845:848 atlA 845:848 Here, we show that subinhibitory concentrations of clindamycin triggered a transcriptional stress response in S. aureus via the alternative sigma factor B (σ(B)) and upregulated the expression of the major biofilm-associated genes atlA, lrgA, agrA, the psm genes, fnbA, and fnbB Our data suggest that subinhibitory concentrations of clindamycin alter the ability of S. aureus to form biofilms and shift the composition of the biofilm matrix toward higher eDNA content. 27458233 5 46 dep genes 839:843 arg1 fnbB 888:891 fnbB 888:891 fnbB 888:891 Here, we show that subinhibitory concentrations of clindamycin triggered a transcriptional stress response in S. aureus via the alternative sigma factor B (σ(B)) and upregulated the expression of the major biofilm-associated genes atlA, lrgA, agrA, the psm genes, fnbA, and fnbB Our data suggest that subinhibitory concentrations of clindamycin alter the ability of S. aureus to form biofilms and shift the composition of the biofilm matrix toward higher eDNA content. 27458233 5 46 dep genes 839:843 arg1 genes 871:875 the psm genes 863:875 the psm genes 863:875 Here, we show that subinhibitory concentrations of clindamycin triggered a transcriptional stress response in S. aureus via the alternative sigma factor B (σ(B)) and upregulated the expression of the major biofilm-associated genes atlA, lrgA, agrA, the psm genes, fnbA, and fnbB Our data suggest that subinhibitory concentrations of clindamycin alter the ability of S. aureus to form biofilms and shift the composition of the biofilm matrix toward higher eDNA content. 27458233 5 46 dep genes 839:843 arg1 lrgA 851:854 lrgA 851:854 lrgA 851:854 Here, we show that subinhibitory concentrations of clindamycin triggered a transcriptional stress response in S. aureus via the alternative sigma factor B (σ(B)) and upregulated the expression of the major biofilm-associated genes atlA, lrgA, agrA, the psm genes, fnbA, and fnbB Our data suggest that subinhibitory concentrations of clindamycin alter the ability of S. aureus to form biofilms and shift the composition of the biofilm matrix toward higher eDNA content. 27458233 5 46 dep genes 839:843 arg1 agrA 857:860 agrA 857:860 agrA 857:860 Here, we show that subinhibitory concentrations of clindamycin triggered a transcriptional stress response in S. aureus via the alternative sigma factor B (σ(B)) and upregulated the expression of the major biofilm-associated genes atlA, lrgA, agrA, the psm genes, fnbA, and fnbB Our data suggest that subinhibitory concentrations of clindamycin alter the ability of S. aureus to form biofilms and shift the composition of the biofilm matrix toward higher eDNA content. 27458233 5 47 theme clindamycin 947:957 arg1 concentrations 929:942 subinhibitory concentrations 915:942 subinhibitory concentrations of clindamycin 915:957 Here, we show that subinhibitory concentrations of clindamycin triggered a transcriptional stress response in S. aureus via the alternative sigma factor B (σ(B)) and upregulated the expression of the major biofilm-associated genes atlA, lrgA, agrA, the psm genes, fnbA, and fnbB Our data suggest that subinhibitory concentrations of clindamycin alter the ability of S. aureus to form biofilms and shift the composition of the biofilm matrix toward higher eDNA content. 27458233 6 48 theme relevant 1228:1235 arg1 antibiotics 1237:1247 clinically relevant antibiotics 1217:1247 clinically relevant antibiotics such as clindamycin 1217:1267 An understanding of the molecular mechanisms underlying biofilm assembly and dispersal in response to subinhibitory concentrations of clinically relevant antibiotics such as clindamycin is critical to further optimize antibiotic treatment strategies of biofilm-associated S. aureus infections. 27458233 6 48 theme relevant 1228:1235 arg1 clindamycin 1257:1267 clindamycin 1257:1267 clindamycin 1257:1267 An understanding of the molecular mechanisms underlying biofilm assembly and dispersal in response to subinhibitory concentrations of clinically relevant antibiotics such as clindamycin is critical to further optimize antibiotic treatment strategies of biofilm-associated S. aureus infections. 27458233 6 49 theme mechanisms 1117:1126 arg1 understanding 1086:1098 An understanding 1083:1098 An understanding of the molecular mechanisms underlying biofilm assembly and dispersal in response to subinhibitory concentrations of clinically relevant antibiotics such as clindamycin 1083:1267 An understanding of the molecular mechanisms underlying biofilm assembly and dispersal in response to subinhibitory concentrations of clinically relevant antibiotics such as clindamycin is critical to further optimize antibiotic treatment strategies of biofilm-associated S. aureus infections. 27458233 6 49 theme mechanisms 1117:1126 arg1 critical 1272:1279 critical 1272:1279 critical 1272:1279 An understanding of the molecular mechanisms underlying biofilm assembly and dispersal in response to subinhibitory concentrations of clinically relevant antibiotics such as clindamycin is critical to further optimize antibiotic treatment strategies of biofilm-associated S. aureus infections. 27458233 3 50 theme immune 350:355 arg1 system 357:362 the immune system 346:362 the immune system 346:362 Bacteria within a biofilm are shielded from the immune system by the formation of an extracellular polymeric matrix, composed of polysaccharides, extracellular DNA (eDNA), and proteins. 27458233 5 51 theme eDNA 1069:1072 arg1 content 1074:1080 higher eDNA content 1062:1080 higher eDNA content 1062:1080 Here, we show that subinhibitory concentrations of clindamycin triggered a transcriptional stress response in S. aureus via the alternative sigma factor B (σ(B)) and upregulated the expression of the major biofilm-associated genes atlA, lrgA, agrA, the psm genes, fnbA, and fnbB Our data suggest that subinhibitory concentrations of clindamycin alter the ability of S. aureus to form biofilms and shift the composition of the biofilm matrix toward higher eDNA content. 27458233 6 52 theme infections 1365:1374 arg1 strategies 1322:1331 antibiotic treatment strategies 1301:1331 antibiotic treatment strategies of biofilm-associated S. aureus infections 1301:1374 An understanding of the molecular mechanisms underlying biofilm assembly and dispersal in response to subinhibitory concentrations of clinically relevant antibiotics such as clindamycin is critical to further optimize antibiotic treatment strategies of biofilm-associated S. aureus infections. 28186408 17 0 theme stability 2698:2706 arg1 modulation 2675:2684 the modulation 2671:2684 the modulation of emulsion stability 2671:2706 Microgels, which reveal interface activity without necessarily being amphiphilic, develop even more complex behavior when located at fluid or solid interfaces: the sensitivity of microgels to various stimuli allows, e.g., the modulation of emulsion stability, adhesion, sensing, and filtration. 28186408 10 1 theme chemical 1314:1321 arg1 functionality 1323:1335 chemical functionality 1314:1335 chemical functionality 1314:1335 Microgels provide the possibility to introduce chemical functionality at different positions. 28186408 17 2 theme complex 2549:2555 arg1 behavior 2557:2564 even more complex behavior 2539:2564 even more complex behavior 2539:2564 Microgels, which reveal interface activity without necessarily being amphiphilic, develop even more complex behavior when located at fluid or solid interfaces: the sensitivity of microgels to various stimuli allows, e.g., the modulation of emulsion stability, adhesion, sensing, and filtration. 28186408 4 3 theme solvent 527:533 arg1 solvent 527:533 solvent 527:533 solvent 527:533 In a collapsed state, they might resemble hard colloids but they can still contain significant amounts of solvent. 28186408 4 3 theme solvent 527:533 arg1 amounts 516:522 significant amounts 504:522 significant amounts of solvent 504:533 In a collapsed state, they might resemble hard colloids but they can still contain significant amounts of solvent. 28186408 11 4 theme combinations 1498:1509 arg1 coexistence 1464:1474 short-range coexistence 1452:1474 short-range coexistence of otherwise instable combinations of chemical reactivity 1452:1532 Combining architectural diversity and compartmentalization of reactive groups enables thus short-range coexistence of otherwise instable combinations of chemical reactivity. 28186408 8 5 theme different 1067:1075 arg1 architecture 1077:1088 a different architecture 1065:1088 a different architecture 1065:1088 The combination of being soft and porous while still having a stable structure through the cross-linked network allows for designing microgels that have the same total chemical composition, but different properties due to a different architecture. 28186408 17 6 dep modulation 2675:2684 arg1 e.g. 2665:2668 e.g. 2665:2668 e.g. 2665:2668 Microgels, which reveal interface activity without necessarily being amphiphilic, develop even more complex behavior when located at fluid or solid interfaces: the sensitivity of microgels to various stimuli allows, e.g., the modulation of emulsion stability, adhesion, sensing, and filtration. 28186408 2 7 theme flexible 245:252 arg1 macromolecules 254:267 flexible macromolecules 245:267 flexible macromolecules 245:267 They are unique systems that are distinctly different from common colloids, such as, e.g., rigid nanoparticles, flexible macromolecules, micelles, or vesicles. 28186408 19 8 theme different 2910:2918 arg1 classes 2920:2926 very different classes 2905:2926 very different classes of materials 2905:2939 In sum, microgels unite properties of very different classes of materials. 28186408 3 9 dep nanometers 374:383 arg1 called 401:406 called 401:406 called "nanogels" 401:417 The size of the microgel networks is in the range of several micrometers down to nanometers (then sometimes called "nanogels"). 28186408 16 10 theme intraparticle 2369:2381 arg1 properties 2383:2392 their intraparticle properties 2363:2392 their intraparticle properties 2363:2392 From a physics point of view, microgels are particularly intriguing and challenging, since their intraparticle properties are intimately linked to their interparticle behavior. 28186408 4 11 contain contain 496:502 arg2 solvent 527:533 solvent 527:533 solvent 527:533 In a collapsed state, they might resemble hard colloids but they can still contain significant amounts of solvent. 28186408 4 11 contain contain 496:502 arg2 amounts 516:522 significant amounts 504:522 significant amounts of solvent 504:533 In a collapsed state, they might resemble hard colloids but they can still contain significant amounts of solvent. 28186408 4 11 contain contain 496:502 arg1 they 481:484 they 481:484 they 481:484 In a collapsed state, they might resemble hard colloids but they can still contain significant amounts of solvent. 28186408 7 12 theme cross-linker 737:748 arg1 content 750:756 the cross-linker content 733:756 the cross-linker content 733:756 Obviously, the cross-linker content will allow control of whether microgels behave more "colloidal" or "macromolecular". 28186408 14 13 theme organic 1900:1906 arg1 solvents 1908:1915 many organic solvents 1895:1915 many organic solvents 1895:1915 The unique ability of microgels to retain their colloidal stability and swelling degree both in water and in many organic solvents allows use of different chemistries for the modification of microgel structure. 28186408 12 14 theme uptake-release 1581:1594 arg1 purposes 1596:1603 uptake-release purposes 1581:1603 uptake-release purposes of active substances 1581:1624 The open microgel structure is beneficial for uptake-release purposes of active substances. 28186408 11 15 theme chemical 1514:1521 arg1 reactivity 1523:1532 chemical reactivity 1514:1532 chemical reactivity 1514:1532 Combining architectural diversity and compartmentalization of reactive groups enables thus short-range coexistence of otherwise instable combinations of chemical reactivity. 28186408 18 16 from fields 2814:2819 arg1 relevance 2782:2790 an ever-increasing relevance 2763:2790 an ever-increasing relevance of microgels in these fields including biomedicine and process technology 2763:2864 Hence, we envision an ever-increasing relevance of microgels in these fields including biomedicine and process technology. 28186408 21 17 theme nature 3250:3255 arg1 independent 3222:3232 independent 3222:3232 independent 3222:3232 This Account focuses on synthetic microgels (mainly based on acrylamides); however, the general, fundamental features of microgels are independent of the chemical nature of the building moieties. 28186408 21 17 theme nature 3250:3255 arg1 features 3196:3203 the general, fundamental features 3171:3203 features 3196:3203 This Account focuses on synthetic microgels (mainly based on acrylamides); however, the general, fundamental features of microgels are independent of the chemical nature of the building moieties. 28186408 22 18 theme worlds 3522:3527 arg1 " 3476:3476 the "best" 3467:3476 the "best" of the colloidal, polymeric, and surfactant worlds 3467:3527 Microgels allow combining features of chemical functionality, structural integrity, macromolecular architecture, adaptivity, permeability, and deformability in a unique way to include the "best" of the colloidal, polymeric, and surfactant worlds. 28186408 21 19 theme fundamental 3184:3194 arg1 independent 3222:3232 independent 3222:3232 independent 3222:3232 This Account focuses on synthetic microgels (mainly based on acrylamides); however, the general, fundamental features of microgels are independent of the chemical nature of the building moieties. 28186408 21 19 theme fundamental 3184:3194 arg1 features 3196:3203 the general, fundamental features 3171:3203 features 3196:3203 This Account focuses on synthetic microgels (mainly based on acrylamides); however, the general, fundamental features of microgels are independent of the chemical nature of the building moieties. 28186408 23 20 theme different 3585:3593 arg1 fields 3595:3600 very different fields 3580:3600 very different fields 3580:3600 This will open the door for novel applications in very different fields such as, e.g., in sensors, catalysis, and separation technology. 28186408 5 21 theme dangling 594:601 arg1 chains 603:608 dangling chains 594:608 dangling chains 594:608 When swollen, they are soft and have a fuzzy surface with dangling chains. 28186408 9 22 dep Microgels 1091:1099 arg1 based 1101:1105 based 1101:1105 based 1101:1105 Microgels based, e.g., on two monomers but have either statistical spatial distribution, or a core-shell or hollow-two-shell morphology will display very different properties. 28186408 9 22 dep Microgels 1091:1099 arg1 have 1134:1137 have 1134:1137 have either statistical spatial distribution, or a core-shell or hollow-two-shell morphology 1134:1225 Microgels based, e.g., on two monomers but have either statistical spatial distribution, or a core-shell or hollow-two-shell morphology will display very different properties. 28186408 11 23 theme short-range 1452:1462 arg1 coexistence 1464:1474 short-range coexistence 1452:1474 short-range coexistence of otherwise instable combinations of chemical reactivity 1452:1532 Combining architectural diversity and compartmentalization of reactive groups enables thus short-range coexistence of otherwise instable combinations of chemical reactivity. 28186408 9 24 theme spatial 1158:1164 arg1 distribution 1166:1177 statistical spatial distribution 1146:1177 statistical spatial distribution 1146:1177 Microgels based, e.g., on two monomers but have either statistical spatial distribution, or a core-shell or hollow-two-shell morphology will display very different properties. 28186408 14 25 theme swelling 1858:1865 arg1 degree 1867:1872 swelling degree 1858:1872 swelling degree 1858:1872 The unique ability of microgels to retain their colloidal stability and swelling degree both in water and in many organic solvents allows use of different chemistries for the modification of microgel structure. 28186408 22 26 theme macromolecular 3367:3380 arg1 features 3309:3316 combining features 3299:3316 combining features of chemical functionality 3299:3342 Microgels allow combining features of chemical functionality, structural integrity, macromolecular architecture, adaptivity, permeability, and deformability in a unique way to include the "best" of the colloidal, polymeric, and surfactant worlds. 28186408 22 26 theme macromolecular 3367:3380 arg1 architecture 3382:3393 macromolecular architecture 3367:3393 macromolecular architecture 3367:3393 Microgels allow combining features of chemical functionality, structural integrity, macromolecular architecture, adaptivity, permeability, and deformability in a unique way to include the "best" of the colloidal, polymeric, and surfactant worlds. 28186408 12 27 theme open 1539:1542 arg1 beneficial 1566:1575 beneficial 1566:1575 beneficial 1566:1575 The open microgel structure is beneficial for uptake-release purposes of active substances. 28186408 12 27 theme open 1539:1542 arg1 structure 1553:1561 The open microgel structure 1535:1561 The open microgel structure 1535:1561 The open microgel structure is beneficial for uptake-release purposes of active substances. 28186408 15 28 theme physicochemical 2244:2258 arg1 properties 2260:2269 their physicochemical properties 2238:2269 their physicochemical properties 2238:2269 The capability of microgels to adjust both their shape and volume in response to external stimuli (e.g., temperature, ionic strength and composition, pH, electrochemical stimulus, pressure, light) provides the opportunity to reversibly tune their physicochemical properties. 28186408 13 29 theme functionalities 1697:1711 arg1 integration 1675:1685 site-selective integration 1660:1685 site-selective integration of active functionalities like reactive groups, charges, or markers 1660:1753 In addition, the openness allows site-selective integration of active functionalities like reactive groups, charges, or markers by postmodification processes. 28186408 11 30 theme instable 1489:1496 arg1 combinations 1498:1509 otherwise instable combinations 1479:1509 otherwise instable combinations of chemical reactivity 1479:1532 Combining architectural diversity and compartmentalization of reactive groups enables thus short-range coexistence of otherwise instable combinations of chemical reactivity. 28186408 16 31 attach linked 2409:2414 arg2 properties 2383:2392 their intraparticle properties 2363:2392 their intraparticle properties 2363:2392 From a physics point of view, microgels are particularly intriguing and challenging, since their intraparticle properties are intimately linked to their interparticle behavior. 28186408 16 31 attach linked 2409:2414 arg1 behavior 2439:2446 their interparticle behavior 2419:2446 their interparticle behavior 2419:2446 From a physics point of view, microgels are particularly intriguing and challenging, since their intraparticle properties are intimately linked to their interparticle behavior. 28186408 22 32 theme polymeric 3496:3504 arg1 worlds 3522:3527 the colloidal, polymeric, and surfactant worlds 3481:3527 the colloidal, polymeric, and surfactant worlds 3481:3527 Microgels allow combining features of chemical functionality, structural integrity, macromolecular architecture, adaptivity, permeability, and deformability in a unique way to include the "best" of the colloidal, polymeric, and surfactant worlds. 28186408 13 33 theme reactive 1718:1725 arg1 groups 1727:1732 reactive groups 1718:1732 reactive groups 1718:1732 In addition, the openness allows site-selective integration of active functionalities like reactive groups, charges, or markers by postmodification processes. 28186408 16 34 from point 2287:2291 arg1 intriguing 2329:2338 intriguing 2329:2338 intriguing 2329:2338 From a physics point of view, microgels are particularly intriguing and challenging, since their intraparticle properties are intimately linked to their interparticle behavior. 28186408 3 35 theme microgel 309:316 arg1 networks 318:325 the microgel networks 305:325 the microgel networks 305:325 The size of the microgel networks is in the range of several micrometers down to nanometers (then sometimes called "nanogels"). 28186408 13 36 theme site-selective 1660:1673 arg1 integration 1675:1685 site-selective integration 1660:1685 site-selective integration of active functionalities like reactive groups, charges, or markers 1660:1753 In addition, the openness allows site-selective integration of active functionalities like reactive groups, charges, or markers by postmodification processes. 28186408 15 37 dep temperature 2102:2112 arg1 e.g. 2096:2099 e.g. 2096:2099 e.g. 2096:2099 The capability of microgels to adjust both their shape and volume in response to external stimuli (e.g., temperature, ionic strength and composition, pH, electrochemical stimulus, pressure, light) provides the opportunity to reversibly tune their physicochemical properties. 28186408 22 38 theme unique 3445:3450 arg1 way 3452:3454 a unique way 3443:3454 a unique way to include the "best" of the colloidal, polymeric, and surfactant worlds 3443:3527 Microgels allow combining features of chemical functionality, structural integrity, macromolecular architecture, adaptivity, permeability, and deformability in a unique way to include the "best" of the colloidal, polymeric, and surfactant worlds. 28186408 0 39 theme Functional 0:9 arg1 Systems 34:40 Functional Microgels and Microgel Systems 0:40 Functional Microgels and Microgel Systems 0:40 Functional Microgels and Microgel Systems. 28186408 20 40 theme different 2973:2981 arg1 macromolecules 2988:3001 very different (bio)macromolecules 2968:3001 very different (bio)macromolecules such as, e.g., polysaccharides, peptides, or DNA 2968:3050 Microgels can be based on very different (bio)macromolecules such as, e.g., polysaccharides, peptides, or DNA, as well as on synthetic polymers. 28186408 20 40 theme different 2973:2981 arg1 peptides 3035:3042 peptides 3035:3042 peptides 3035:3042 Microgels can be based on very different (bio)macromolecules such as, e.g., polysaccharides, peptides, or DNA, as well as on synthetic polymers. 28186408 20 40 theme different 2973:2981 arg1 bio 2984:2986 bio 2984:2986 bio 2984:2986 Microgels can be based on very different (bio)macromolecules such as, e.g., polysaccharides, peptides, or DNA, as well as on synthetic polymers. 28186408 20 40 theme different 2973:2981 arg1 polysaccharides 3018:3032 polysaccharides 3018:3032 polysaccharides 3018:3032 Microgels can be based on very different (bio)macromolecules such as, e.g., polysaccharides, peptides, or DNA, as well as on synthetic polymers. 28186408 20 40 theme different 2973:2981 arg1 DNA 3048:3050 DNA 3048:3050 DNA 3048:3050 Microgels can be based on very different (bio)macromolecules such as, e.g., polysaccharides, peptides, or DNA, as well as on synthetic polymers. 28186408 23 41 theme novel 3558:3562 arg1 applications 3564:3575 novel applications 3558:3575 novel applications 3558:3575 This will open the door for novel applications in very different fields such as, e.g., in sensors, catalysis, and separation technology. 28186408 11 42 theme reactive 1423:1430 arg1 groups 1432:1437 reactive groups 1423:1437 reactive groups 1423:1437 Combining architectural diversity and compartmentalization of reactive groups enables thus short-range coexistence of otherwise instable combinations of chemical reactivity. 28186408 14 43 theme microgels 1808:1816 arg1 ability 1797:1803 The unique ability 1786:1803 The unique ability of microgels to retain their colloidal stability and swelling degree both in water and in many organic solvents 1786:1915 The unique ability of microgels to retain their colloidal stability and swelling degree both in water and in many organic solvents allows use of different chemistries for the modification of microgel structure. 28186408 14 44 theme structure 1986:1994 arg1 modification 1961:1972 the modification 1957:1972 the modification of microgel structure 1957:1994 The unique ability of microgels to retain their colloidal stability and swelling degree both in water and in many organic solvents allows use of different chemistries for the modification of microgel structure. 28186408 21 45 theme synthetic 3111:3119 arg1 microgels 3121:3129 synthetic microgels 3111:3129 synthetic microgels (mainly based on acrylamides) 3111:3159 This Account focuses on synthetic microgels (mainly based on acrylamides); however, the general, fundamental features of microgels are independent of the chemical nature of the building moieties. 28186408 18 46 from microgels 2795:2803 arg1 biomedicine 2831:2841 biomedicine 2831:2841 biomedicine 2831:2841 Hence, we envision an ever-increasing relevance of microgels in these fields including biomedicine and process technology. 28186408 18 46 from microgels 2795:2803 arg1 technology 2855:2864 process technology 2847:2864 process technology 2847:2864 Hence, we envision an ever-increasing relevance of microgels in these fields including biomedicine and process technology. 28186408 18 46 from microgels 2795:2803 arg1 fields 2814:2819 these fields 2808:2819 these fields including biomedicine and process technology 2808:2864 Hence, we envision an ever-increasing relevance of microgels in these fields including biomedicine and process technology. 28186408 15 47 theme ionic 2115:2119 arg1 temperature 2102:2112 temperature 2102:2112 temperature 2102:2112 The capability of microgels to adjust both their shape and volume in response to external stimuli (e.g., temperature, ionic strength and composition, pH, electrochemical stimulus, pressure, light) provides the opportunity to reversibly tune their physicochemical properties. 28186408 15 47 theme ionic 2115:2119 arg1 strength 2121:2128 ionic strength 2115:2128 ionic strength 2115:2128 The capability of microgels to adjust both their shape and volume in response to external stimuli (e.g., temperature, ionic strength and composition, pH, electrochemical stimulus, pressure, light) provides the opportunity to reversibly tune their physicochemical properties. 28186408 21 48 theme microgels 3208:3216 arg1 independent 3222:3232 independent 3222:3232 independent 3222:3232 This Account focuses on synthetic microgels (mainly based on acrylamides); however, the general, fundamental features of microgels are independent of the chemical nature of the building moieties. 28186408 21 48 theme microgels 3208:3216 arg1 features 3196:3203 the general, fundamental features 3171:3203 features 3196:3203 This Account focuses on synthetic microgels (mainly based on acrylamides); however, the general, fundamental features of microgels are independent of the chemical nature of the building moieties. 28186408 3 49 theme micrometers 354:364 arg1 range 337:341 the range 333:341 the range of several micrometers down to nanometers (then sometimes called "nanogels") 333:418 The size of the microgel networks is in the range of several micrometers down to nanometers (then sometimes called "nanogels"). 28186408 8 50 theme same 1000:1003 arg1 composition 1020:1030 the same total chemical composition 996:1030 the same total chemical composition 996:1030 The combination of being soft and porous while still having a stable structure through the cross-linked network allows for designing microgels that have the same total chemical composition, but different properties due to a different architecture. 28186408 3 51 dep called 401:406 arg1 sometimes 391:399 sometimes 391:399 sometimes 391:399 The size of the microgel networks is in the range of several micrometers down to nanometers (then sometimes called "nanogels"). 28186408 17 52 from interfaces 2597:2606 arg1 located 2571:2577 located 2571:2577 located 2571:2577 Microgels, which reveal interface activity without necessarily being amphiphilic, develop even more complex behavior when located at fluid or solid interfaces: the sensitivity of microgels to various stimuli allows, e.g., the modulation of emulsion stability, adhesion, sensing, and filtration. 28186408 21 53 theme general 3175:3181 arg1 independent 3222:3232 independent 3222:3232 independent 3222:3232 This Account focuses on synthetic microgels (mainly based on acrylamides); however, the general, fundamental features of microgels are independent of the chemical nature of the building moieties. 28186408 21 53 theme general 3175:3181 arg1 features 3196:3203 the general, fundamental features 3171:3203 features 3196:3203 This Account focuses on synthetic microgels (mainly based on acrylamides); however, the general, fundamental features of microgels are independent of the chemical nature of the building moieties. 28186408 22 54 theme colloidal 3485:3493 arg1 worlds 3522:3527 the colloidal, polymeric, and surfactant worlds 3481:3527 the colloidal, polymeric, and surfactant worlds 3481:3527 Microgels allow combining features of chemical functionality, structural integrity, macromolecular architecture, adaptivity, permeability, and deformability in a unique way to include the "best" of the colloidal, polymeric, and surfactant worlds. 28186408 8 55 theme chemical 1011:1018 arg1 composition 1020:1030 the same total chemical composition 996:1030 the same total chemical composition 996:1030 The combination of being soft and porous while still having a stable structure through the cross-linked network allows for designing microgels that have the same total chemical composition, but different properties due to a different architecture. 28186408 14 56 theme chemistries 1941:1951 arg1 use 1924:1926 use 1924:1926 use of different chemistries 1924:1951 The unique ability of microgels to retain their colloidal stability and swelling degree both in water and in many organic solvents allows use of different chemistries for the modification of microgel structure. 28186408 23 57 theme separation 3644:3653 arg1 technology 3655:3664 separation technology 3644:3664 separation technology 3644:3664 This will open the door for novel applications in very different fields such as, e.g., in sensors, catalysis, and separation technology. 28186408 22 58 dep way 3452:3454 arg1 include 3459:3465 include 3459:3465 to include the "best" of the colloidal, polymeric, and surfactant worlds 3456:3527 Microgels allow combining features of chemical functionality, structural integrity, macromolecular architecture, adaptivity, permeability, and deformability in a unique way to include the "best" of the colloidal, polymeric, and surfactant worlds. 28186408 8 59 contain have 991:994 arg2 composition 1020:1030 the same total chemical composition 996:1030 the same total chemical composition 996:1030 The combination of being soft and porous while still having a stable structure through the cross-linked network allows for designing microgels that have the same total chemical composition, but different properties due to a different architecture. 28186408 8 59 contain have 991:994 arg1 microgels 976:984 microgels 976:984 microgels that have the same total chemical composition, but different properties due to a different architecture 976:1088 The combination of being soft and porous while still having a stable structure through the cross-linked network allows for designing microgels that have the same total chemical composition, but different properties due to a different architecture. 28186408 8 59 contain have 991:994 arg2 properties 1047:1056 different properties 1037:1056 different properties 1037:1056 The combination of being soft and porous while still having a stable structure through the cross-linked network allows for designing microgels that have the same total chemical composition, but different properties due to a different architecture. 28186408 7 60 theme colloidal 811:819 arg1 " 820:820 "colloidal" 810:820 "colloidal" 810:820 Obviously, the cross-linker content will allow control of whether microgels behave more "colloidal" or "macromolecular". 28186408 5 61 with surface 581:587 arg1 chains 603:608 dangling chains 594:608 dangling chains 594:608 When swollen, they are soft and have a fuzzy surface with dangling chains. 28186408 5 62 contain have 568:571 arg2 surface 581:587 a fuzzy surface 573:587 a fuzzy surface with dangling chains 573:608 When swollen, they are soft and have a fuzzy surface with dangling chains. 28186408 5 62 contain have 568:571 arg1 they 550:553 they 550:553 they 550:553 When swollen, they are soft and have a fuzzy surface with dangling chains. 28186408 16 63 theme interparticle 2425:2437 arg1 behavior 2439:2446 their interparticle behavior 2419:2446 their interparticle behavior 2419:2446 From a physics point of view, microgels are particularly intriguing and challenging, since their intraparticle properties are intimately linked to their interparticle behavior. 28186408 22 64 theme best 3472:3475 arg1 " 3476:3476 the "best" 3467:3476 the "best" of the colloidal, polymeric, and surfactant worlds 3467:3527 Microgels allow combining features of chemical functionality, structural integrity, macromolecular architecture, adaptivity, permeability, and deformability in a unique way to include the "best" of the colloidal, polymeric, and surfactant worlds. 28186408 8 65 theme different 1037:1045 arg1 properties 1047:1056 different properties 1037:1056 different properties 1037:1056 The combination of being soft and porous while still having a stable structure through the cross-linked network allows for designing microgels that have the same total chemical composition, but different properties due to a different architecture. 28186408 17 66 theme more 2544:2547 arg1 behavior 2557:2564 even more complex behavior 2539:2564 even more complex behavior 2539:2564 Microgels, which reveal interface activity without necessarily being amphiphilic, develop even more complex behavior when located at fluid or solid interfaces: the sensitivity of microgels to various stimuli allows, e.g., the modulation of emulsion stability, adhesion, sensing, and filtration. 28186408 4 67 theme significant 504:514 arg1 solvent 527:533 solvent 527:533 solvent 527:533 In a collapsed state, they might resemble hard colloids but they can still contain significant amounts of solvent. 28186408 4 67 theme significant 504:514 arg1 amounts 516:522 significant amounts 504:522 significant amounts of solvent 504:533 In a collapsed state, they might resemble hard colloids but they can still contain significant amounts of solvent. 28186408 16 68 theme view 2296:2299 arg1 point 2287:2291 a physics point 2277:2291 a physics point of view 2277:2299 From a physics point of view, microgels are particularly intriguing and challenging, since their intraparticle properties are intimately linked to their interparticle behavior. 28186408 18 69 theme ever-increasing 2766:2780 arg1 relevance 2782:2790 an ever-increasing relevance 2763:2790 an ever-increasing relevance of microgels in these fields including biomedicine and process technology 2763:2864 Hence, we envision an ever-increasing relevance of microgels in these fields including biomedicine and process technology. 28186408 5 70 theme fuzzy 575:579 arg1 surface 581:587 a fuzzy surface 573:587 a fuzzy surface with dangling chains 573:608 When swollen, they are soft and have a fuzzy surface with dangling chains. 28186408 11 71 theme reactivity 1523:1532 arg1 combinations 1498:1509 otherwise instable combinations 1479:1509 otherwise instable combinations of chemical reactivity 1479:1532 Combining architectural diversity and compartmentalization of reactive groups enables thus short-range coexistence of otherwise instable combinations of chemical reactivity. 28186408 18 72 from relevance 2782:2790 arg1 biomedicine 2831:2841 biomedicine 2831:2841 biomedicine 2831:2841 Hence, we envision an ever-increasing relevance of microgels in these fields including biomedicine and process technology. 28186408 18 72 from relevance 2782:2790 arg1 technology 2855:2864 process technology 2847:2864 process technology 2847:2864 Hence, we envision an ever-increasing relevance of microgels in these fields including biomedicine and process technology. 28186408 18 72 from relevance 2782:2790 arg1 fields 2814:2819 these fields 2808:2819 these fields including biomedicine and process technology 2808:2864 Hence, we envision an ever-increasing relevance of microgels in these fields including biomedicine and process technology. 28186408 22 73 theme structural 3345:3354 arg1 features 3309:3316 combining features 3299:3316 combining features of chemical functionality 3299:3342 Microgels allow combining features of chemical functionality, structural integrity, macromolecular architecture, adaptivity, permeability, and deformability in a unique way to include the "best" of the colloidal, polymeric, and surfactant worlds. 28186408 22 73 theme structural 3345:3354 arg1 integrity 3356:3364 structural integrity 3345:3364 structural integrity 3345:3364 Microgels allow combining features of chemical functionality, structural integrity, macromolecular architecture, adaptivity, permeability, and deformability in a unique way to include the "best" of the colloidal, polymeric, and surfactant worlds. 28186408 2 74 theme unique 142:147 arg1 They 133:136 They 133:136 They 133:136 They are unique systems that are distinctly different from common colloids, such as, e.g., rigid nanoparticles, flexible macromolecules, micelles, or vesicles. 28186408 2 74 theme unique 142:147 arg1 systems 149:155 unique systems 142:155 unique systems that are distinctly different from common colloids, such as, e.g., rigid nanoparticles, flexible macromolecules, micelles, or vesicles 142:290 They are unique systems that are distinctly different from common colloids, such as, e.g., rigid nanoparticles, flexible macromolecules, micelles, or vesicles. 28186408 6 75 theme branched 703:710 arg1 polymers 712:719 linear and (hyper)branched polymers 685:719 linear and (hyper)branched polymers 685:719 The presence of cross-links provides structural integrity, in contrast to linear and (hyper)branched polymers. 28186408 15 76 theme electrochemical 2151:2165 arg1 temperature 2102:2112 temperature 2102:2112 temperature 2102:2112 The capability of microgels to adjust both their shape and volume in response to external stimuli (e.g., temperature, ionic strength and composition, pH, electrochemical stimulus, pressure, light) provides the opportunity to reversibly tune their physicochemical properties. 28186408 15 76 theme electrochemical 2151:2165 arg1 stimulus 2167:2174 electrochemical stimulus 2151:2174 electrochemical stimulus 2151:2174 The capability of microgels to adjust both their shape and volume in response to external stimuli (e.g., temperature, ionic strength and composition, pH, electrochemical stimulus, pressure, light) provides the opportunity to reversibly tune their physicochemical properties. 28186408 2 77 from colloids 199:206 arg1 different 177:185 different 177:185 different 177:185 They are unique systems that are distinctly different from common colloids, such as, e.g., rigid nanoparticles, flexible macromolecules, micelles, or vesicles. 28186408 21 78 theme moieties 3273:3280 arg1 nature 3250:3255 the chemical nature 3237:3255 the chemical nature of the building moieties 3237:3280 This Account focuses on synthetic microgels (mainly based on acrylamides); however, the general, fundamental features of microgels are independent of the chemical nature of the building moieties. 28186408 21 79 theme building 3264:3271 arg1 moieties 3273:3280 the building moieties 3260:3280 the building moieties 3260:3280 This Account focuses on synthetic microgels (mainly based on acrylamides); however, the general, fundamental features of microgels are independent of the chemical nature of the building moieties. 28186408 10 80 theme different 1340:1348 arg1 positions 1350:1358 different positions 1340:1358 different positions 1340:1358 Microgels provide the possibility to introduce chemical functionality at different positions. 28186408 22 81 theme functionality 3330:3342 arg1 architecture 3382:3393 macromolecular architecture 3367:3393 macromolecular architecture 3367:3393 Microgels allow combining features of chemical functionality, structural integrity, macromolecular architecture, adaptivity, permeability, and deformability in a unique way to include the "best" of the colloidal, polymeric, and surfactant worlds. 28186408 22 81 theme functionality 3330:3342 arg1 deformability 3426:3438 deformability 3426:3438 deformability 3426:3438 Microgels allow combining features of chemical functionality, structural integrity, macromolecular architecture, adaptivity, permeability, and deformability in a unique way to include the "best" of the colloidal, polymeric, and surfactant worlds. 28186408 22 81 theme functionality 3330:3342 arg1 adaptivity 3396:3405 adaptivity 3396:3405 adaptivity 3396:3405 Microgels allow combining features of chemical functionality, structural integrity, macromolecular architecture, adaptivity, permeability, and deformability in a unique way to include the "best" of the colloidal, polymeric, and surfactant worlds. 28186408 22 81 theme functionality 3330:3342 arg1 permeability 3408:3419 permeability 3408:3419 permeability 3408:3419 Microgels allow combining features of chemical functionality, structural integrity, macromolecular architecture, adaptivity, permeability, and deformability in a unique way to include the "best" of the colloidal, polymeric, and surfactant worlds. 28186408 22 81 theme functionality 3330:3342 arg1 features 3309:3316 combining features 3299:3316 combining features of chemical functionality 3299:3342 Microgels allow combining features of chemical functionality, structural integrity, macromolecular architecture, adaptivity, permeability, and deformability in a unique way to include the "best" of the colloidal, polymeric, and surfactant worlds. 28186408 22 81 theme functionality 3330:3342 arg1 integrity 3356:3364 structural integrity 3345:3364 structural integrity 3345:3364 Microgels allow combining features of chemical functionality, structural integrity, macromolecular architecture, adaptivity, permeability, and deformability in a unique way to include the "best" of the colloidal, polymeric, and surfactant worlds. 28186408 23 82 dep such 3602:3605 arg1 as 3607:3608 as 3607:3608 as 3607:3608 This will open the door for novel applications in very different fields such as, e.g., in sensors, catalysis, and separation technology. 28186408 8 83 theme stable 905:910 arg1 structure 912:920 a stable structure 903:920 a stable structure 903:920 The combination of being soft and porous while still having a stable structure through the cross-linked network allows for designing microgels that have the same total chemical composition, but different properties due to a different architecture. 28186408 13 84 theme postmodification 1758:1773 arg1 processes 1775:1783 postmodification processes 1758:1783 postmodification processes 1758:1783 In addition, the openness allows site-selective integration of active functionalities like reactive groups, charges, or markers by postmodification processes. 28186408 14 85 theme many 1895:1898 arg1 solvents 1908:1915 many organic solvents 1895:1915 many organic solvents 1895:1915 The unique ability of microgels to retain their colloidal stability and swelling degree both in water and in many organic solvents allows use of different chemistries for the modification of microgel structure. 28186408 12 86 theme active 1608:1613 arg1 substances 1615:1624 active substances 1608:1624 active substances 1608:1624 The open microgel structure is beneficial for uptake-release purposes of active substances. 28186408 19 87 theme materials 2931:2939 arg1 classes 2920:2926 very different classes 2905:2926 very different classes of materials 2905:2939 In sum, microgels unite properties of very different classes of materials. 28186408 22 88 theme chemical 3321:3328 arg1 functionality 3330:3342 chemical functionality 3321:3342 chemical functionality 3321:3342 Microgels allow combining features of chemical functionality, structural integrity, macromolecular architecture, adaptivity, permeability, and deformability in a unique way to include the "best" of the colloidal, polymeric, and surfactant worlds. 28186408 22 89 theme combining 3299:3307 arg1 architecture 3382:3393 macromolecular architecture 3367:3393 macromolecular architecture 3367:3393 Microgels allow combining features of chemical functionality, structural integrity, macromolecular architecture, adaptivity, permeability, and deformability in a unique way to include the "best" of the colloidal, polymeric, and surfactant worlds. 28186408 22 89 theme combining 3299:3307 arg1 deformability 3426:3438 deformability 3426:3438 deformability 3426:3438 Microgels allow combining features of chemical functionality, structural integrity, macromolecular architecture, adaptivity, permeability, and deformability in a unique way to include the "best" of the colloidal, polymeric, and surfactant worlds. 28186408 22 89 theme combining 3299:3307 arg1 adaptivity 3396:3405 adaptivity 3396:3405 adaptivity 3396:3405 Microgels allow combining features of chemical functionality, structural integrity, macromolecular architecture, adaptivity, permeability, and deformability in a unique way to include the "best" of the colloidal, polymeric, and surfactant worlds. 28186408 22 89 theme combining 3299:3307 arg1 permeability 3408:3419 permeability 3408:3419 permeability 3408:3419 Microgels allow combining features of chemical functionality, structural integrity, macromolecular architecture, adaptivity, permeability, and deformability in a unique way to include the "best" of the colloidal, polymeric, and surfactant worlds. 28186408 22 89 theme combining 3299:3307 arg1 features 3309:3316 combining features 3299:3316 combining features of chemical functionality 3299:3342 Microgels allow combining features of chemical functionality, structural integrity, macromolecular architecture, adaptivity, permeability, and deformability in a unique way to include the "best" of the colloidal, polymeric, and surfactant worlds. 28186408 22 89 theme combining 3299:3307 arg1 integrity 3356:3364 structural integrity 3345:3364 structural integrity 3345:3364 Microgels allow combining features of chemical functionality, structural integrity, macromolecular architecture, adaptivity, permeability, and deformability in a unique way to include the "best" of the colloidal, polymeric, and surfactant worlds. 28186408 19 90 theme classes 2920:2926 arg1 properties 2891:2900 properties 2891:2900 properties of very different classes of materials 2891:2939 In sum, microgels unite properties of very different classes of materials. 28186408 22 91 theme surfactant 3511:3520 arg1 worlds 3522:3527 the colloidal, polymeric, and surfactant worlds 3481:3527 the colloidal, polymeric, and surfactant worlds 3481:3527 Microgels allow combining features of chemical functionality, structural integrity, macromolecular architecture, adaptivity, permeability, and deformability in a unique way to include the "best" of the colloidal, polymeric, and surfactant worlds. 28186408 18 92 theme process 2847:2853 arg1 technology 2855:2864 process technology 2847:2864 process technology 2847:2864 Hence, we envision an ever-increasing relevance of microgels in these fields including biomedicine and process technology. 28186408 16 93 theme physics 2279:2285 arg1 point 2287:2291 a physics point 2277:2291 a physics point of view 2277:2299 From a physics point of view, microgels are particularly intriguing and challenging, since their intraparticle properties are intimately linked to their interparticle behavior. 28186408 9 94 theme statistical 1146:1156 arg1 distribution 1166:1177 statistical spatial distribution 1146:1177 statistical spatial distribution 1146:1177 Microgels based, e.g., on two monomers but have either statistical spatial distribution, or a core-shell or hollow-two-shell morphology will display very different properties. 28186408 17 95 theme emulsion 2689:2696 arg1 stability 2698:2706 emulsion stability 2689:2706 emulsion stability 2689:2706 Microgels, which reveal interface activity without necessarily being amphiphilic, develop even more complex behavior when located at fluid or solid interfaces: the sensitivity of microgels to various stimuli allows, e.g., the modulation of emulsion stability, adhesion, sensing, and filtration. 28186408 17 96 theme microgels 2628:2636 arg1 sensitivity 2613:2623 the sensitivity 2609:2623 the sensitivity of microgels to various stimuli 2609:2655 Microgels, which reveal interface activity without necessarily being amphiphilic, develop even more complex behavior when located at fluid or solid interfaces: the sensitivity of microgels to various stimuli allows, e.g., the modulation of emulsion stability, adhesion, sensing, and filtration. 28186408 17 97 theme interface 2473:2481 arg1 activity 2483:2490 interface activity 2473:2490 interface activity 2473:2490 Microgels, which reveal interface activity without necessarily being amphiphilic, develop even more complex behavior when located at fluid or solid interfaces: the sensitivity of microgels to various stimuli allows, e.g., the modulation of emulsion stability, adhesion, sensing, and filtration. 28186408 11 98 theme groups 1432:1437 arg1 compartmentalization 1399:1418 compartmentalization 1399:1418 compartmentalization 1399:1418 Combining architectural diversity and compartmentalization of reactive groups enables thus short-range coexistence of otherwise instable combinations of chemical reactivity. 28186408 11 98 theme groups 1432:1437 arg1 diversity 1385:1393 diversity 1385:1393 diversity 1385:1393 Combining architectural diversity and compartmentalization of reactive groups enables thus short-range coexistence of otherwise instable combinations of chemical reactivity. 28186408 2 99 theme rigid 224:228 arg1 nanoparticles 230:242 rigid nanoparticles 224:242 rigid nanoparticles 224:242 They are unique systems that are distinctly different from common colloids, such as, e.g., rigid nanoparticles, flexible macromolecules, micelles, or vesicles. 28186408 12 100 theme microgel 1544:1551 arg1 beneficial 1566:1575 beneficial 1566:1575 beneficial 1566:1575 The open microgel structure is beneficial for uptake-release purposes of active substances. 28186408 12 100 theme microgel 1544:1551 arg1 structure 1553:1561 The open microgel structure 1535:1561 The open microgel structure 1535:1561 The open microgel structure is beneficial for uptake-release purposes of active substances. 28186408 17 101 theme various 2641:2647 arg1 stimuli 2649:2655 various stimuli 2641:2655 various stimuli 2641:2655 Microgels, which reveal interface activity without necessarily being amphiphilic, develop even more complex behavior when located at fluid or solid interfaces: the sensitivity of microgels to various stimuli allows, e.g., the modulation of emulsion stability, adhesion, sensing, and filtration. 28186408 11 102 theme otherwise 1479:1487 arg1 combinations 1498:1509 otherwise instable combinations 1479:1509 otherwise instable combinations of chemical reactivity 1479:1532 Combining architectural diversity and compartmentalization of reactive groups enables thus short-range coexistence of otherwise instable combinations of chemical reactivity. 28186408 14 103 theme colloidal 1834:1842 arg1 stability 1844:1852 colloidal stability 1834:1852 colloidal stability 1834:1852 The unique ability of microgels to retain their colloidal stability and swelling degree both in water and in many organic solvents allows use of different chemistries for the modification of microgel structure. 28186408 9 104 theme core-shell 1185:1194 arg1 morphology 1216:1225 a core-shell or hollow-two-shell morphology 1183:1225 a core-shell or hollow-two-shell morphology 1183:1225 Microgels based, e.g., on two monomers but have either statistical spatial distribution, or a core-shell or hollow-two-shell morphology will display very different properties. 28186408 8 105 theme cross-linked 934:945 arg1 network 947:953 the cross-linked network 930:953 the cross-linked network 930:953 The combination of being soft and porous while still having a stable structure through the cross-linked network allows for designing microgels that have the same total chemical composition, but different properties due to a different architecture. 28186408 1 106 theme macromolecular 57:70 arg1 Microgels 43:51 Microgels 43:51 Microgels 43:51 Microgels are macromolecular networks swollen by the solvent in which they are dissolved. 28186408 1 106 theme macromolecular 57:70 arg1 networks 72:79 macromolecular networks 57:79 macromolecular networks swollen by the solvent in which they are dissolved 57:130 Microgels are macromolecular networks swollen by the solvent in which they are dissolved. 28186408 20 107 theme synthetic 3067:3075 arg1 polymers 3077:3084 synthetic polymers 3067:3084 synthetic polymers 3067:3084 Microgels can be based on very different (bio)macromolecules such as, e.g., polysaccharides, peptides, or DNA, as well as on synthetic polymers. 28186408 11 108 theme architectural 1371:1383 arg1 diversity 1385:1393 diversity 1385:1393 diversity 1385:1393 Combining architectural diversity and compartmentalization of reactive groups enables thus short-range coexistence of otherwise instable combinations of chemical reactivity. 28186408 6 109 theme cross-links 627:637 arg1 presence 615:622 The presence 611:622 The presence of cross-links 611:637 The presence of cross-links provides structural integrity, in contrast to linear and (hyper)branched polymers. 28186408 3 110 theme networks 318:325 arg1 size 297:300 The size 293:300 The size of the microgel networks 293:325 The size of the microgel networks is in the range of several micrometers down to nanometers (then sometimes called "nanogels"). 28186408 4 111 theme collapsed 426:434 arg1 state 436:440 a collapsed state 424:440 a collapsed state 424:440 In a collapsed state, they might resemble hard colloids but they can still contain significant amounts of solvent. 28186408 21 112 theme chemical 3241:3248 arg1 nature 3250:3255 the chemical nature 3237:3255 the chemical nature of the building moieties 3237:3280 This Account focuses on synthetic microgels (mainly based on acrylamides); however, the general, fundamental features of microgels are independent of the chemical nature of the building moieties. 28186408 17 113 theme fluid 2582:2586 arg1 interfaces 2597:2606 fluid or solid interfaces 2582:2606 fluid or solid interfaces 2582:2606 Microgels, which reveal interface activity without necessarily being amphiphilic, develop even more complex behavior when located at fluid or solid interfaces: the sensitivity of microgels to various stimuli allows, e.g., the modulation of emulsion stability, adhesion, sensing, and filtration. 28186408 0 114 theme Microgels 11:19 arg1 Systems 34:40 Functional Microgels and Microgel Systems 0:40 Functional Microgels and Microgel Systems 0:40 Functional Microgels and Microgel Systems. 28186408 9 115 theme hollow-two-shell 1199:1214 arg1 morphology 1216:1225 a core-shell or hollow-two-shell morphology 1183:1225 a core-shell or hollow-two-shell morphology 1183:1225 Microgels based, e.g., on two monomers but have either statistical spatial distribution, or a core-shell or hollow-two-shell morphology will display very different properties. 28186408 3 116 theme several 346:352 arg1 micrometers 354:364 several micrometers 346:364 several micrometers down to nanometers (then sometimes called "nanogels") 346:418 The size of the microgel networks is in the range of several micrometers down to nanometers (then sometimes called "nanogels"). 28186408 13 117 theme active 1690:1695 arg1 functionalities 1697:1711 active functionalities 1690:1711 active functionalities like reactive groups, charges, or markers 1690:1753 In addition, the openness allows site-selective integration of active functionalities like reactive groups, charges, or markers by postmodification processes. 28186408 17 118 theme solid 2591:2595 arg1 interfaces 2597:2606 fluid or solid interfaces 2582:2606 fluid or solid interfaces 2582:2606 Microgels, which reveal interface activity without necessarily being amphiphilic, develop even more complex behavior when located at fluid or solid interfaces: the sensitivity of microgels to various stimuli allows, e.g., the modulation of emulsion stability, adhesion, sensing, and filtration. 28186408 0 119 theme Microgel 25:32 arg1 Systems 34:40 Functional Microgels and Microgel Systems 0:40 Functional Microgels and Microgel Systems 0:40 Functional Microgels and Microgel Systems. 28186408 15 120 theme external 2078:2085 arg1 stimuli 2087:2093 external stimuli 2078:2093 external stimuli (e.g., temperature, ionic strength and composition, pH, electrochemical stimulus, pressure, light) 2078:2192 The capability of microgels to adjust both their shape and volume in response to external stimuli (e.g., temperature, ionic strength and composition, pH, electrochemical stimulus, pressure, light) provides the opportunity to reversibly tune their physicochemical properties. 28186408 7 121 theme macromolecular 826:839 arg1 " 840:840 "macromolecular" 825:840 "macromolecular" 825:840 Obviously, the cross-linker content will allow control of whether microgels behave more "colloidal" or "macromolecular". 28186408 12 122 theme substances 1615:1624 arg1 purposes 1596:1603 uptake-release purposes 1581:1603 uptake-release purposes of active substances 1581:1624 The open microgel structure is beneficial for uptake-release purposes of active substances. 28186408 14 123 theme microgel 1977:1984 arg1 structure 1986:1994 microgel structure 1977:1994 microgel structure 1977:1994 The unique ability of microgels to retain their colloidal stability and swelling degree both in water and in many organic solvents allows use of different chemistries for the modification of microgel structure. 28186408 9 124 theme different 1245:1253 arg1 properties 1255:1264 very different properties 1240:1264 very different properties 1240:1264 Microgels based, e.g., on two monomers but have either statistical spatial distribution, or a core-shell or hollow-two-shell morphology will display very different properties. 28186408 4 125 theme hard 463:466 arg1 colloids 468:475 hard colloids 463:475 hard colloids 463:475 In a collapsed state, they might resemble hard colloids but they can still contain significant amounts of solvent. 28186408 15 126 theme microgels 2015:2023 arg1 capability 2001:2010 The capability 1997:2010 The capability of microgels to adjust both their shape and volume in response to external stimuli (e.g., temperature, ionic strength and composition, pH, electrochemical stimulus, pressure, light) 1997:2192 The capability of microgels to adjust both their shape and volume in response to external stimuli (e.g., temperature, ionic strength and composition, pH, electrochemical stimulus, pressure, light) provides the opportunity to reversibly tune their physicochemical properties. 28186408 6 127 theme linear 685:690 arg1 polymers 712:719 linear and (hyper)branched polymers 685:719 linear and (hyper)branched polymers 685:719 The presence of cross-links provides structural integrity, in contrast to linear and (hyper)branched polymers. 28186408 3 128 theme nanogels 409:416 arg1 " 417:417 nanogels" 409:417 nanogels" 409:417 The size of the microgel networks is in the range of several micrometers down to nanometers (then sometimes called "nanogels"). 28186408 14 129 theme unique 1790:1795 arg1 ability 1797:1803 The unique ability 1786:1803 The unique ability of microgels to retain their colloidal stability and swelling degree both in water and in many organic solvents 1786:1915 The unique ability of microgels to retain their colloidal stability and swelling degree both in water and in many organic solvents allows use of different chemistries for the modification of microgel structure. 28186408 8 130 theme total 1005:1009 arg1 composition 1020:1030 the same total chemical composition 996:1030 the same total chemical composition 996:1030 The combination of being soft and porous while still having a stable structure through the cross-linked network allows for designing microgels that have the same total chemical composition, but different properties due to a different architecture. 28186408 3 131 theme down 366:369 arg1 micrometers 354:364 several micrometers 346:364 several micrometers down to nanometers (then sometimes called "nanogels") 346:418 The size of the microgel networks is in the range of several micrometers down to nanometers (then sometimes called "nanogels"). 28186408 18 132 theme microgels 2795:2803 arg1 relevance 2782:2790 an ever-increasing relevance 2763:2790 an ever-increasing relevance of microgels in these fields including biomedicine and process technology 2763:2864 Hence, we envision an ever-increasing relevance of microgels in these fields including biomedicine and process technology. 28186408 8 133 link cross-linked 934:945 arg1 network 947:953 the cross-linked network 930:953 the cross-linked network 930:953 The combination of being soft and porous while still having a stable structure through the cross-linked network allows for designing microgels that have the same total chemical composition, but different properties due to a different architecture. 28186408 23 134 from door 3549:3552 arg1 fields 3595:3600 very different fields 3580:3600 very different fields 3580:3600 This will open the door for novel applications in very different fields such as, e.g., in sensors, catalysis, and separation technology. 28186408 2 135 theme common 192:197 arg1 nanoparticles 230:242 rigid nanoparticles 224:242 rigid nanoparticles 224:242 They are unique systems that are distinctly different from common colloids, such as, e.g., rigid nanoparticles, flexible macromolecules, micelles, or vesicles. 28186408 2 135 theme common 192:197 arg1 micelles 270:277 micelles 270:277 micelles 270:277 They are unique systems that are distinctly different from common colloids, such as, e.g., rigid nanoparticles, flexible macromolecules, micelles, or vesicles. 28186408 2 135 theme common 192:197 arg1 colloids 199:206 common colloids 192:206 common colloids 192:206 They are unique systems that are distinctly different from common colloids, such as, e.g., rigid nanoparticles, flexible macromolecules, micelles, or vesicles. 28186408 2 135 theme common 192:197 arg1 macromolecules 254:267 flexible macromolecules 245:267 flexible macromolecules 245:267 They are unique systems that are distinctly different from common colloids, such as, e.g., rigid nanoparticles, flexible macromolecules, micelles, or vesicles. 28186408 2 135 theme common 192:197 arg1 vesicles 283:290 vesicles 283:290 vesicles 283:290 They are unique systems that are distinctly different from common colloids, such as, e.g., rigid nanoparticles, flexible macromolecules, micelles, or vesicles. 28186408 14 136 theme different 1931:1939 arg1 chemistries 1941:1951 different chemistries 1931:1951 different chemistries 1931:1951 The unique ability of microgels to retain their colloidal stability and swelling degree both in water and in many organic solvents allows use of different chemistries for the modification of microgel structure. 28186408 6 137 theme structural 648:657 arg1 integrity 659:667 structural integrity 648:667 structural integrity 648:667 The presence of cross-links provides structural integrity, in contrast to linear and (hyper)branched polymers. 26582205 4 0 theme N-linked 900:907 arg1 residues 955:962 H-Lys13-Try1; 16 amino acid residues 927:962 H-Lys13-Try1; 16 amino acid residues 927:962 Sequential digestion of TIB-141 with lysyl endopeptidase and trypsin resulted in the identification of a glycopeptide (H-Lys13-Try3; 48 amino acid residues) with a single N-linked oligosaccharide near the N terminus capable of neutralizing the effect of galectin-9 and another glycopeptide with two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity. 26582205 4 0 theme N-linked 900:907 arg1 oligosaccharides 909:924 two N-linked oligosaccharides 896:924 two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity 896:985 Sequential digestion of TIB-141 with lysyl endopeptidase and trypsin resulted in the identification of a glycopeptide (H-Lys13-Try3; 48 amino acid residues) with a single N-linked oligosaccharide near the N terminus capable of neutralizing the effect of galectin-9 and another glycopeptide with two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity. 26582205 6 1 theme residues 1149:1156 arg1 Removal 1109:1115 Removal 1109:1115 Removal of the C-terminal 38 amino acid residues of H-Lys13-Try3 with glutamyl endopeptidase 1109:1200 Removal of the C-terminal 38 amino acid residues of H-Lys13-Try3 with glutamyl endopeptidase, however, also resulted in loss of the activity. 26582205 2 2 theme responsible 363:373 arg1 glycans 355:361 IgE glycans 351:361 IgE glycans responsible for the galectin-9-induced suppression using mouse monoclonal IgE (TIB-141) 351:449 To elucidate the mechanism of the interaction in detail, we focused on identification and structural analysis of IgE glycans responsible for the galectin-9-induced suppression using mouse monoclonal IgE (TIB-141). 26582205 4 3 theme TIB-141 625:631 arg1 digestion 612:620 Sequential digestion 601:620 Sequential digestion of TIB-141 with lysyl endopeptidase and trypsin 601:668 Sequential digestion of TIB-141 with lysyl endopeptidase and trypsin resulted in the identification of a glycopeptide (H-Lys13-Try3; 48 amino acid residues) with a single N-linked oligosaccharide near the N terminus capable of neutralizing the effect of galectin-9 and another glycopeptide with two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity. 26582205 4 4 gly glycopeptide 706:717 arg2 glycopeptide 706:717 a glycopeptide 704:717 a glycopeptide (H-Lys13-Try3; 48 amino acid residues) with a single N-linked oligosaccharide near the N terminus capable of neutralizing the effect of galectin-9 and another glycopeptide with two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity 704:985 Sequential digestion of TIB-141 with lysyl endopeptidase and trypsin resulted in the identification of a glycopeptide (H-Lys13-Try3; 48 amino acid residues) with a single N-linked oligosaccharide near the N terminus capable of neutralizing the effect of galectin-9 and another glycopeptide with two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity. 26582205 4 4 gly glycopeptide 706:717 arg2 residues 748:755 H-Lys13-Try3; 48 amino acid residues 720:755 H-Lys13-Try3; 48 amino acid residues 720:755 Sequential digestion of TIB-141 with lysyl endopeptidase and trypsin resulted in the identification of a glycopeptide (H-Lys13-Try3; 48 amino acid residues) with a single N-linked oligosaccharide near the N terminus capable of neutralizing the effect of galectin-9 and another glycopeptide with two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity. 26582205 7 5 theme oligosaccharides 1292:1307 arg1 structures 1269:1278 the structures 1265:1278 the structures of N-linked oligosaccharides of H-Lys13-Try1 1265:1323 We determined the structures of N-linked oligosaccharides of H-Lys13-Try1. 26582205 5 6 from H-Lys13-Try3 1044:1055 arg1 elimination 998:1008 Enzymatic elimination 988:1008 Enzymatic elimination of the oligosaccharide chain from H-Lys13-Try3 and H-Lys13-Try1 988:1072 Enzymatic elimination of the oligosaccharide chain from H-Lys13-Try3 and H-Lys13-Try1 completely abolished the activity. 26582205 8 7 theme oligosaccharides 1377:1392 arg1 fraction 1349:1356 The galectin-9-binding fraction 1326:1356 The galectin-9-binding fraction of pyridylaminated oligosaccharides 1326:1392 The galectin-9-binding fraction of pyridylaminated oligosaccharides contained asialo- and monosialylated bi/tri-antennary complex type oligosaccharides with a core fucose residue. 26582205 10 8 theme polypeptide 1941:1951 arg1 structures 1953:1962 neighboring polypeptide structures 1929:1962 neighboring polypeptide structures of TIB-141 1929:1973 Although the oligosaccharides linked to H-Lys13-Try3 could not be fully characterized, these results indicate the possibility that cooperative binding of oligosaccharide and neighboring polypeptide structures of TIB-141 to galectin-9 affects the overall affinity and specificity of the IgE-lectin interaction. 26582205 1 9 theme cells 187:191 arg1 degranulation 165:177 degranulation 165:177 degranulation of mast cells 165:191 We previously showed that galectin-9 suppresses degranulation of mast cells through protein-glycan interaction with IgE. 26582205 4 10 theme glycopeptide 706:717 arg1 identification 686:699 the identification 682:699 the identification of a glycopeptide (H-Lys13-Try3; 48 amino acid residues) with a single N-linked oligosaccharide near the N terminus capable of neutralizing the effect of galectin-9 and another glycopeptide with two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity 682:985 Sequential digestion of TIB-141 with lysyl endopeptidase and trypsin resulted in the identification of a glycopeptide (H-Lys13-Try3; 48 amino acid residues) with a single N-linked oligosaccharide near the N terminus capable of neutralizing the effect of galectin-9 and another glycopeptide with two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity. 26582205 1 11 theme protein-glycan 201:214 arg1 interaction 216:226 protein-glycan interaction 201:226 protein-glycan interaction with IgE 201:235 We previously showed that galectin-9 suppresses degranulation of mast cells through protein-glycan interaction with IgE. 26582205 8 12 theme galectin-9-binding 1330:1347 arg1 fraction 1349:1356 The galectin-9-binding fraction 1326:1356 The galectin-9-binding fraction of pyridylaminated oligosaccharides 1326:1392 The galectin-9-binding fraction of pyridylaminated oligosaccharides contained asialo- and monosialylated bi/tri-antennary complex type oligosaccharides with a core fucose residue. 26582205 7 13 link N-linked 1283:1290 arg1 oligosaccharides 1292:1307 N-linked oligosaccharides 1283:1307 N-linked oligosaccharides of H-Lys13-Try1 1283:1323 We determined the structures of N-linked oligosaccharides of H-Lys13-Try1. 26582205 5 14 from H-Lys13-Try1 1061:1072 arg1 elimination 998:1008 Enzymatic elimination 988:1008 Enzymatic elimination of the oligosaccharide chain from H-Lys13-Try3 and H-Lys13-Try1 988:1072 Enzymatic elimination of the oligosaccharide chain from H-Lys13-Try3 and H-Lys13-Try1 completely abolished the activity. 26582205 4 15 theme amino 737:741 arg1 residues 748:755 H-Lys13-Try3; 48 amino acid residues 720:755 H-Lys13-Try3; 48 amino acid residues 720:755 Sequential digestion of TIB-141 with lysyl endopeptidase and trypsin resulted in the identification of a glycopeptide (H-Lys13-Try3; 48 amino acid residues) with a single N-linked oligosaccharide near the N terminus capable of neutralizing the effect of galectin-9 and another glycopeptide with two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity. 26582205 4 15 theme amino 737:741 arg1 glycopeptide 706:717 a glycopeptide 704:717 a glycopeptide (H-Lys13-Try3; 48 amino acid residues) with a single N-linked oligosaccharide near the N terminus capable of neutralizing the effect of galectin-9 and another glycopeptide with two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity 704:985 Sequential digestion of TIB-141 with lysyl endopeptidase and trypsin resulted in the identification of a glycopeptide (H-Lys13-Try3; 48 amino acid residues) with a single N-linked oligosaccharide near the N terminus capable of neutralizing the effect of galectin-9 and another glycopeptide with two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity. 26582205 6 16 theme H-Lys13-Try3 1161:1172 arg1 H-Lys13-Try3 1161:1172 H-Lys13-Try3 1161:1172 H-Lys13-Try3 1161:1172 Removal of the C-terminal 38 amino acid residues of H-Lys13-Try3 with glutamyl endopeptidase, however, also resulted in loss of the activity. 26582205 6 16 theme H-Lys13-Try3 1161:1172 arg1 residues 1149:1156 the C-terminal 38 amino acid residues 1120:1156 the C-terminal 38 amino acid residues of H-Lys13-Try3 1120:1172 Removal of the C-terminal 38 amino acid residues of H-Lys13-Try3 with glutamyl endopeptidase, however, also resulted in loss of the activity. 26582205 4 17 theme acid 743:746 arg1 residues 748:755 H-Lys13-Try3; 48 amino acid residues 720:755 H-Lys13-Try3; 48 amino acid residues 720:755 Sequential digestion of TIB-141 with lysyl endopeptidase and trypsin resulted in the identification of a glycopeptide (H-Lys13-Try3; 48 amino acid residues) with a single N-linked oligosaccharide near the N terminus capable of neutralizing the effect of galectin-9 and another glycopeptide with two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity. 26582205 4 17 theme acid 743:746 arg1 glycopeptide 706:717 a glycopeptide 704:717 a glycopeptide (H-Lys13-Try3; 48 amino acid residues) with a single N-linked oligosaccharide near the N terminus capable of neutralizing the effect of galectin-9 and another glycopeptide with two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity 704:985 Sequential digestion of TIB-141 with lysyl endopeptidase and trypsin resulted in the identification of a glycopeptide (H-Lys13-Try3; 48 amino acid residues) with a single N-linked oligosaccharide near the N terminus capable of neutralizing the effect of galectin-9 and another glycopeptide with two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity. 26582205 9 18 with oligosaccharides 1710:1725 arg1 residue 1746:1752 a core fucose residue 1732:1752 a core fucose residue 1732:1752 The structures of the oligosaccharides were consistent with the sugar-binding specificity of galectin-9, whereas the nonbinding fraction contained monosialylated and disialylated biantennary complex type oligosaccharides with a core fucose residue. 26582205 10 19 theme overall 2001:2007 arg1 affinity 2009:2016 affinity 2009:2016 affinity 2009:2016 Although the oligosaccharides linked to H-Lys13-Try3 could not be fully characterized, these results indicate the possibility that cooperative binding of oligosaccharide and neighboring polypeptide structures of TIB-141 to galectin-9 affects the overall affinity and specificity of the IgE-lectin interaction. 26582205 4 20 theme amino 944:948 arg1 residues 955:962 H-Lys13-Try1; 16 amino acid residues 927:962 H-Lys13-Try1; 16 amino acid residues 927:962 Sequential digestion of TIB-141 with lysyl endopeptidase and trypsin resulted in the identification of a glycopeptide (H-Lys13-Try3; 48 amino acid residues) with a single N-linked oligosaccharide near the N terminus capable of neutralizing the effect of galectin-9 and another glycopeptide with two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity. 26582205 4 20 theme amino 944:948 arg1 oligosaccharides 909:924 two N-linked oligosaccharides 896:924 two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity 896:985 Sequential digestion of TIB-141 with lysyl endopeptidase and trypsin resulted in the identification of a glycopeptide (H-Lys13-Try3; 48 amino acid residues) with a single N-linked oligosaccharide near the N terminus capable of neutralizing the effect of galectin-9 and another glycopeptide with two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity. 26582205 3 21 with combination 463:473 arg1 antigen 484:490 the antigen 480:490 the antigen 480:490 TIB-141 in combination with the antigen induced degranulation of RBL-2H3 cells, which was almost completely inhibited by human and mouse galectin-9. 26582205 2 22 theme interaction 272:282 arg1 mechanism 255:263 the mechanism 251:263 the mechanism of the interaction in detail 251:292 To elucidate the mechanism of the interaction in detail, we focused on identification and structural analysis of IgE glycans responsible for the galectin-9-induced suppression using mouse monoclonal IgE (TIB-141). 26582205 3 23 dep human 573:577 arg1 galectin-9 589:598 galectin-9 589:598 galectin-9 589:598 TIB-141 in combination with the antigen induced degranulation of RBL-2H3 cells, which was almost completely inhibited by human and mouse galectin-9. 26582205 4 24 with effect 845:850 arg1 residues 955:962 H-Lys13-Try1; 16 amino acid residues 927:962 H-Lys13-Try1; 16 amino acid residues 927:962 Sequential digestion of TIB-141 with lysyl endopeptidase and trypsin resulted in the identification of a glycopeptide (H-Lys13-Try3; 48 amino acid residues) with a single N-linked oligosaccharide near the N terminus capable of neutralizing the effect of galectin-9 and another glycopeptide with two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity. 26582205 4 24 with effect 845:850 arg1 oligosaccharides 909:924 two N-linked oligosaccharides 896:924 two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity 896:985 Sequential digestion of TIB-141 with lysyl endopeptidase and trypsin resulted in the identification of a glycopeptide (H-Lys13-Try3; 48 amino acid residues) with a single N-linked oligosaccharide near the N terminus capable of neutralizing the effect of galectin-9 and another glycopeptide with two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity. 26582205 7 25 theme N-linked 1283:1290 arg1 oligosaccharides 1292:1307 N-linked oligosaccharides 1283:1307 N-linked oligosaccharides of H-Lys13-Try1 1283:1323 We determined the structures of N-linked oligosaccharides of H-Lys13-Try1. 26582205 8 26 theme complex 1448:1454 arg1 oligosaccharides 1461:1476 bi/tri-antennary complex type oligosaccharides 1431:1476 bi/tri-antennary complex type oligosaccharides 1431:1476 The galectin-9-binding fraction of pyridylaminated oligosaccharides contained asialo- and monosialylated bi/tri-antennary complex type oligosaccharides with a core fucose residue. 26582205 9 27 theme complex 1697:1703 arg1 oligosaccharides 1710:1725 biantennary complex type oligosaccharides 1685:1725 biantennary complex type oligosaccharides with a core fucose residue 1685:1752 The structures of the oligosaccharides were consistent with the sugar-binding specificity of galectin-9, whereas the nonbinding fraction contained monosialylated and disialylated biantennary complex type oligosaccharides with a core fucose residue. 26582205 10 28 attach linked 1785:1790 arg1 H-Lys13-Try3 1795:1806 H-Lys13-Try3 1795:1806 H-Lys13-Try3 1795:1806 Although the oligosaccharides linked to H-Lys13-Try3 could not be fully characterized, these results indicate the possibility that cooperative binding of oligosaccharide and neighboring polypeptide structures of TIB-141 to galectin-9 affects the overall affinity and specificity of the IgE-lectin interaction. 26582205 10 28 attach linked 1785:1790 arg2 oligosaccharides 1768:1783 the oligosaccharides 1764:1783 the oligosaccharides linked to H-Lys13-Try3 1764:1806 Although the oligosaccharides linked to H-Lys13-Try3 could not be fully characterized, these results indicate the possibility that cooperative binding of oligosaccharide and neighboring polypeptide structures of TIB-141 to galectin-9 affects the overall affinity and specificity of the IgE-lectin interaction. 26582205 9 29 dep contained 1643:1651 arg1 disialylated 1672:1683 disialylated 1672:1683 disialylated 1672:1683 The structures of the oligosaccharides were consistent with the sugar-binding specificity of galectin-9, whereas the nonbinding fraction contained monosialylated and disialylated biantennary complex type oligosaccharides with a core fucose residue. 26582205 9 29 dep contained 1643:1651 arg1 monosialylated 1653:1666 monosialylated 1653:1666 monosialylated 1653:1666 The structures of the oligosaccharides were consistent with the sugar-binding specificity of galectin-9, whereas the nonbinding fraction contained monosialylated and disialylated biantennary complex type oligosaccharides with a core fucose residue. 26582205 9 30 dep disialylated 1672:1683 arg1 oligosaccharides 1710:1725 biantennary complex type oligosaccharides 1685:1725 biantennary complex type oligosaccharides with a core fucose residue 1685:1752 The structures of the oligosaccharides were consistent with the sugar-binding specificity of galectin-9, whereas the nonbinding fraction contained monosialylated and disialylated biantennary complex type oligosaccharides with a core fucose residue. 26582205 4 31 theme N 806:806 arg1 terminus 808:815 the N terminus 802:815 the N terminus capable of neutralizing the effect of galectin-9 and another glycopeptide with two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity 802:985 Sequential digestion of TIB-141 with lysyl endopeptidase and trypsin resulted in the identification of a glycopeptide (H-Lys13-Try3; 48 amino acid residues) with a single N-linked oligosaccharide near the N terminus capable of neutralizing the effect of galectin-9 and another glycopeptide with two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity. 26582205 2 32 theme monoclonal 426:435 arg1 TIB-141 442:448 TIB-141 442:448 TIB-141 442:448 To elucidate the mechanism of the interaction in detail, we focused on identification and structural analysis of IgE glycans responsible for the galectin-9-induced suppression using mouse monoclonal IgE (TIB-141). 26582205 2 32 theme monoclonal 426:435 arg1 IgE 437:439 mouse monoclonal IgE 420:439 mouse monoclonal IgE (TIB-141) 420:449 To elucidate the mechanism of the interaction in detail, we focused on identification and structural analysis of IgE glycans responsible for the galectin-9-induced suppression using mouse monoclonal IgE (TIB-141). 26582205 5 33 theme oligosaccharide 1017:1031 arg1 chain 1033:1037 the oligosaccharide chain 1013:1037 the oligosaccharide chain 1013:1037 Enzymatic elimination of the oligosaccharide chain from H-Lys13-Try3 and H-Lys13-Try1 completely abolished the activity. 26582205 2 34 from mechanism 255:263 arg1 detail 287:292 detail 287:292 detail 287:292 To elucidate the mechanism of the interaction in detail, we focused on identification and structural analysis of IgE glycans responsible for the galectin-9-induced suppression using mouse monoclonal IgE (TIB-141). 26582205 8 35 theme fucose 1490:1495 arg1 residue 1497:1503 a core fucose residue 1483:1503 a core fucose residue 1483:1503 The galectin-9-binding fraction of pyridylaminated oligosaccharides contained asialo- and monosialylated bi/tri-antennary complex type oligosaccharides with a core fucose residue. 26582205 0 36 theme Cooperative 0:10 arg1 Interactions 12:23 Cooperative Interactions 0:23 Cooperative Interactions of Oligosaccharide and Peptide Moieties of a Glycopeptide 0:81 Cooperative Interactions of Oligosaccharide and Peptide Moieties of a Glycopeptide Derived from IgE with Galectin-9. 26582205 9 37 theme fucose 1739:1744 arg1 residue 1746:1752 a core fucose residue 1732:1752 a core fucose residue 1732:1752 The structures of the oligosaccharides were consistent with the sugar-binding specificity of galectin-9, whereas the nonbinding fraction contained monosialylated and disialylated biantennary complex type oligosaccharides with a core fucose residue. 26582205 4 38 theme N-linked 772:779 arg1 oligosaccharide 781:795 a single N-linked oligosaccharide 763:795 a single N-linked oligosaccharide near the N terminus capable of neutralizing the effect of galectin-9 and another glycopeptide with two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity 763:985 Sequential digestion of TIB-141 with lysyl endopeptidase and trypsin resulted in the identification of a glycopeptide (H-Lys13-Try3; 48 amino acid residues) with a single N-linked oligosaccharide near the N terminus capable of neutralizing the effect of galectin-9 and another glycopeptide with two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity. 26582205 10 39 theme neighboring 1929:1939 arg1 structures 1953:1962 neighboring polypeptide structures 1929:1962 neighboring polypeptide structures of TIB-141 1929:1973 Although the oligosaccharides linked to H-Lys13-Try3 could not be fully characterized, these results indicate the possibility that cooperative binding of oligosaccharide and neighboring polypeptide structures of TIB-141 to galectin-9 affects the overall affinity and specificity of the IgE-lectin interaction. 26582205 5 40 theme Enzymatic 988:996 arg1 elimination 998:1008 Enzymatic elimination 988:1008 Enzymatic elimination of the oligosaccharide chain from H-Lys13-Try3 and H-Lys13-Try1 988:1072 Enzymatic elimination of the oligosaccharide chain from H-Lys13-Try3 and H-Lys13-Try1 completely abolished the activity. 26582205 4 41 theme galectin-9 855:864 arg1 glycopeptide 878:889 another glycopeptide 870:889 another glycopeptide with two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity 870:985 Sequential digestion of TIB-141 with lysyl endopeptidase and trypsin resulted in the identification of a glycopeptide (H-Lys13-Try3; 48 amino acid residues) with a single N-linked oligosaccharide near the N terminus capable of neutralizing the effect of galectin-9 and another glycopeptide with two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity. 26582205 4 41 theme galectin-9 855:864 arg1 effect 845:850 the effect 841:850 the effect of galectin-9 841:864 Sequential digestion of TIB-141 with lysyl endopeptidase and trypsin resulted in the identification of a glycopeptide (H-Lys13-Try3; 48 amino acid residues) with a single N-linked oligosaccharide near the N terminus capable of neutralizing the effect of galectin-9 and another glycopeptide with two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity. 26582205 3 42 theme RBL-2H3 517:523 arg1 cells 525:529 RBL-2H3 cells 517:529 RBL-2H3 cells 517:529 TIB-141 in combination with the antigen induced degranulation of RBL-2H3 cells, which was almost completely inhibited by human and mouse galectin-9. 26582205 0 43 theme Moieties 56:63 arg1 Interactions 12:23 Cooperative Interactions 0:23 Cooperative Interactions of Oligosaccharide and Peptide Moieties of a Glycopeptide 0:81 Cooperative Interactions of Oligosaccharide and Peptide Moieties of a Glycopeptide Derived from IgE with Galectin-9. 26582205 4 44 theme capable 817:823 arg1 terminus 808:815 the N terminus 802:815 the N terminus capable of neutralizing the effect of galectin-9 and another glycopeptide with two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity 802:985 Sequential digestion of TIB-141 with lysyl endopeptidase and trypsin resulted in the identification of a glycopeptide (H-Lys13-Try3; 48 amino acid residues) with a single N-linked oligosaccharide near the N terminus capable of neutralizing the effect of galectin-9 and another glycopeptide with two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity. 26582205 10 45 theme cooperative 1886:1896 arg1 binding 1898:1904 cooperative binding 1886:1904 cooperative binding of oligosaccharide and neighboring polypeptide structures of TIB-141 to galectin-9 1886:1987 Although the oligosaccharides linked to H-Lys13-Try3 could not be fully characterized, these results indicate the possibility that cooperative binding of oligosaccharide and neighboring polypeptide structures of TIB-141 to galectin-9 affects the overall affinity and specificity of the IgE-lectin interaction. 26582205 3 46 from TIB-141 452:458 arg1 combination 463:473 combination 463:473 combination with the antigen 463:490 TIB-141 in combination with the antigen induced degranulation of RBL-2H3 cells, which was almost completely inhibited by human and mouse galectin-9. 26582205 2 47 theme galectin-9-induced 383:400 arg1 suppression 402:412 the galectin-9-induced suppression 379:412 the galectin-9-induced suppression using mouse monoclonal IgE (TIB-141) 379:449 To elucidate the mechanism of the interaction in detail, we focused on identification and structural analysis of IgE glycans responsible for the galectin-9-induced suppression using mouse monoclonal IgE (TIB-141). 26582205 9 48 theme sugar-binding 1570:1582 arg1 specificity 1584:1594 the sugar-binding specificity 1566:1594 the sugar-binding specificity of galectin-9 1566:1608 The structures of the oligosaccharides were consistent with the sugar-binding specificity of galectin-9, whereas the nonbinding fraction contained monosialylated and disialylated biantennary complex type oligosaccharides with a core fucose residue. 26582205 10 49 theme IgE-lectin 2041:2050 arg1 interaction 2052:2062 the IgE-lectin interaction 2037:2062 the IgE-lectin interaction 2037:2062 Although the oligosaccharides linked to H-Lys13-Try3 could not be fully characterized, these results indicate the possibility that cooperative binding of oligosaccharide and neighboring polypeptide structures of TIB-141 to galectin-9 affects the overall affinity and specificity of the IgE-lectin interaction. 26582205 10 50 theme oligosaccharide 1909:1923 arg1 binding 1898:1904 cooperative binding 1886:1904 cooperative binding of oligosaccharide and neighboring polypeptide structures of TIB-141 to galectin-9 1886:1987 Although the oligosaccharides linked to H-Lys13-Try3 could not be fully characterized, these results indicate the possibility that cooperative binding of oligosaccharide and neighboring polypeptide structures of TIB-141 to galectin-9 affects the overall affinity and specificity of the IgE-lectin interaction. 26582205 9 51 theme oligosaccharides 1528:1543 arg1 consistent 1550:1559 consistent 1550:1559 consistent 1550:1559 The structures of the oligosaccharides were consistent with the sugar-binding specificity of galectin-9, whereas the nonbinding fraction contained monosialylated and disialylated biantennary complex type oligosaccharides with a core fucose residue. 26582205 9 51 theme oligosaccharides 1528:1543 arg1 structures 1510:1519 The structures 1506:1519 The structures of the oligosaccharides 1506:1543 The structures of the oligosaccharides were consistent with the sugar-binding specificity of galectin-9, whereas the nonbinding fraction contained monosialylated and disialylated biantennary complex type oligosaccharides with a core fucose residue. 26582205 6 52 theme acid 1144:1147 arg1 H-Lys13-Try3 1161:1172 H-Lys13-Try3 1161:1172 H-Lys13-Try3 1161:1172 Removal of the C-terminal 38 amino acid residues of H-Lys13-Try3 with glutamyl endopeptidase, however, also resulted in loss of the activity. 26582205 6 52 theme acid 1144:1147 arg1 residues 1149:1156 the C-terminal 38 amino acid residues 1120:1156 the C-terminal 38 amino acid residues of H-Lys13-Try3 1120:1172 Removal of the C-terminal 38 amino acid residues of H-Lys13-Try3 with glutamyl endopeptidase, however, also resulted in loss of the activity. 26582205 4 53 theme Sequential 601:610 arg1 digestion 612:620 Sequential digestion 601:620 Sequential digestion of TIB-141 with lysyl endopeptidase and trypsin 601:668 Sequential digestion of TIB-141 with lysyl endopeptidase and trypsin resulted in the identification of a glycopeptide (H-Lys13-Try3; 48 amino acid residues) with a single N-linked oligosaccharide near the N terminus capable of neutralizing the effect of galectin-9 and another glycopeptide with two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity. 26582205 10 54 theme TIB-141 1967:1973 arg1 oligosaccharide 1909:1923 oligosaccharide 1909:1923 oligosaccharide 1909:1923 Although the oligosaccharides linked to H-Lys13-Try3 could not be fully characterized, these results indicate the possibility that cooperative binding of oligosaccharide and neighboring polypeptide structures of TIB-141 to galectin-9 affects the overall affinity and specificity of the IgE-lectin interaction. 26582205 10 54 theme TIB-141 1967:1973 arg1 structures 1953:1962 neighboring polypeptide structures 1929:1962 neighboring polypeptide structures of TIB-141 1929:1973 Although the oligosaccharides linked to H-Lys13-Try3 could not be fully characterized, these results indicate the possibility that cooperative binding of oligosaccharide and neighboring polypeptide structures of TIB-141 to galectin-9 affects the overall affinity and specificity of the IgE-lectin interaction. 26582205 2 55 theme glycans 355:361 arg1 identification 309:322 identification 309:322 identification 309:322 To elucidate the mechanism of the interaction in detail, we focused on identification and structural analysis of IgE glycans responsible for the galectin-9-induced suppression using mouse monoclonal IgE (TIB-141). 26582205 2 55 theme glycans 355:361 arg1 analysis 339:346 structural analysis 328:346 structural analysis 328:346 To elucidate the mechanism of the interaction in detail, we focused on identification and structural analysis of IgE glycans responsible for the galectin-9-induced suppression using mouse monoclonal IgE (TIB-141). 26582205 10 56 theme structures 1953:1962 arg1 binding 1898:1904 cooperative binding 1886:1904 cooperative binding of oligosaccharide and neighboring polypeptide structures of TIB-141 to galectin-9 1886:1987 Although the oligosaccharides linked to H-Lys13-Try3 could not be fully characterized, these results indicate the possibility that cooperative binding of oligosaccharide and neighboring polypeptide structures of TIB-141 to galectin-9 affects the overall affinity and specificity of the IgE-lectin interaction. 26582205 1 57 theme mast 182:185 arg1 cells 187:191 mast cells 182:191 mast cells 182:191 We previously showed that galectin-9 suppresses degranulation of mast cells through protein-glycan interaction with IgE. 26582205 2 58 theme structural 328:337 arg1 analysis 339:346 structural analysis 328:346 structural analysis 328:346 To elucidate the mechanism of the interaction in detail, we focused on identification and structural analysis of IgE glycans responsible for the galectin-9-induced suppression using mouse monoclonal IgE (TIB-141). 26582205 4 59 link N-linked 900:907 arg1 residues 955:962 H-Lys13-Try1; 16 amino acid residues 927:962 H-Lys13-Try1; 16 amino acid residues 927:962 Sequential digestion of TIB-141 with lysyl endopeptidase and trypsin resulted in the identification of a glycopeptide (H-Lys13-Try3; 48 amino acid residues) with a single N-linked oligosaccharide near the N terminus capable of neutralizing the effect of galectin-9 and another glycopeptide with two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity. 26582205 4 59 link N-linked 900:907 arg1 oligosaccharides 909:924 two N-linked oligosaccharides 896:924 two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity 896:985 Sequential digestion of TIB-141 with lysyl endopeptidase and trypsin resulted in the identification of a glycopeptide (H-Lys13-Try3; 48 amino acid residues) with a single N-linked oligosaccharide near the N terminus capable of neutralizing the effect of galectin-9 and another glycopeptide with two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity. 26582205 0 60 with IgE 96:98 arg1 Galectin-9 105:114 Galectin-9 105:114 Galectin-9 105:114 Cooperative Interactions of Oligosaccharide and Peptide Moieties of a Glycopeptide Derived from IgE with Galectin-9. 26582205 9 61 theme galectin-9 1599:1608 arg1 specificity 1584:1594 the sugar-binding specificity 1566:1594 the sugar-binding specificity of galectin-9 1566:1608 The structures of the oligosaccharides were consistent with the sugar-binding specificity of galectin-9, whereas the nonbinding fraction contained monosialylated and disialylated biantennary complex type oligosaccharides with a core fucose residue. 26582205 4 62 theme acid 950:953 arg1 residues 955:962 H-Lys13-Try1; 16 amino acid residues 927:962 H-Lys13-Try1; 16 amino acid residues 927:962 Sequential digestion of TIB-141 with lysyl endopeptidase and trypsin resulted in the identification of a glycopeptide (H-Lys13-Try3; 48 amino acid residues) with a single N-linked oligosaccharide near the N terminus capable of neutralizing the effect of galectin-9 and another glycopeptide with two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity. 26582205 4 62 theme acid 950:953 arg1 oligosaccharides 909:924 two N-linked oligosaccharides 896:924 two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity 896:985 Sequential digestion of TIB-141 with lysyl endopeptidase and trypsin resulted in the identification of a glycopeptide (H-Lys13-Try3; 48 amino acid residues) with a single N-linked oligosaccharide near the N terminus capable of neutralizing the effect of galectin-9 and another glycopeptide with two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity. 26582205 2 63 theme IgE 351:353 arg1 glycans 355:361 IgE glycans 351:361 IgE glycans responsible for the galectin-9-induced suppression using mouse monoclonal IgE (TIB-141) 351:449 To elucidate the mechanism of the interaction in detail, we focused on identification and structural analysis of IgE glycans responsible for the galectin-9-induced suppression using mouse monoclonal IgE (TIB-141). 26582205 4 64 gly glycopeptide 878:889 arg1 galectin-9 855:864 galectin-9 855:864 galectin-9 855:864 Sequential digestion of TIB-141 with lysyl endopeptidase and trypsin resulted in the identification of a glycopeptide (H-Lys13-Try3; 48 amino acid residues) with a single N-linked oligosaccharide near the N terminus capable of neutralizing the effect of galectin-9 and another glycopeptide with two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity. 26582205 4 64 gly glycopeptide 878:889 arg2 glycopeptide 878:889 another glycopeptide 870:889 another glycopeptide with two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity 870:985 Sequential digestion of TIB-141 with lysyl endopeptidase and trypsin resulted in the identification of a glycopeptide (H-Lys13-Try3; 48 amino acid residues) with a single N-linked oligosaccharide near the N terminus capable of neutralizing the effect of galectin-9 and another glycopeptide with two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity. 26582205 9 65 theme nonbinding 1623:1632 arg1 fraction 1634:1641 the nonbinding fraction 1619:1641 the nonbinding fraction 1619:1641 The structures of the oligosaccharides were consistent with the sugar-binding specificity of galectin-9, whereas the nonbinding fraction contained monosialylated and disialylated biantennary complex type oligosaccharides with a core fucose residue. 26582205 4 66 theme H-Lys13-Try1 927:938 arg1 residues 955:962 H-Lys13-Try1; 16 amino acid residues 927:962 H-Lys13-Try1; 16 amino acid residues 927:962 Sequential digestion of TIB-141 with lysyl endopeptidase and trypsin resulted in the identification of a glycopeptide (H-Lys13-Try3; 48 amino acid residues) with a single N-linked oligosaccharide near the N terminus capable of neutralizing the effect of galectin-9 and another glycopeptide with two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity. 26582205 4 66 theme H-Lys13-Try1 927:938 arg1 oligosaccharides 909:924 two N-linked oligosaccharides 896:924 two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity 896:985 Sequential digestion of TIB-141 with lysyl endopeptidase and trypsin resulted in the identification of a glycopeptide (H-Lys13-Try3; 48 amino acid residues) with a single N-linked oligosaccharide near the N terminus capable of neutralizing the effect of galectin-9 and another glycopeptide with two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity. 26582205 8 67 theme pyridylaminated 1361:1375 arg1 oligosaccharides 1377:1392 pyridylaminated oligosaccharides 1361:1392 pyridylaminated oligosaccharides 1361:1392 The galectin-9-binding fraction of pyridylaminated oligosaccharides contained asialo- and monosialylated bi/tri-antennary complex type oligosaccharides with a core fucose residue. 26582205 10 68 theme interaction 2052:2062 arg1 specificity 2022:2032 specificity 2022:2032 specificity 2022:2032 Although the oligosaccharides linked to H-Lys13-Try3 could not be fully characterized, these results indicate the possibility that cooperative binding of oligosaccharide and neighboring polypeptide structures of TIB-141 to galectin-9 affects the overall affinity and specificity of the IgE-lectin interaction. 26582205 10 68 theme interaction 2052:2062 arg1 affinity 2009:2016 affinity 2009:2016 affinity 2009:2016 Although the oligosaccharides linked to H-Lys13-Try3 could not be fully characterized, these results indicate the possibility that cooperative binding of oligosaccharide and neighboring polypeptide structures of TIB-141 to galectin-9 affects the overall affinity and specificity of the IgE-lectin interaction. 26582205 2 69 from detail 287:292 arg1 mechanism 255:263 the mechanism 251:263 the mechanism of the interaction in detail 251:292 To elucidate the mechanism of the interaction in detail, we focused on identification and structural analysis of IgE glycans responsible for the galectin-9-induced suppression using mouse monoclonal IgE (TIB-141). 26582205 0 70 theme Glycopeptide 70:81 arg1 Oligosaccharide 28:42 Oligosaccharide 28:42 Oligosaccharide 28:42 Cooperative Interactions of Oligosaccharide and Peptide Moieties of a Glycopeptide Derived from IgE with Galectin-9. 26582205 0 70 theme Glycopeptide 70:81 arg1 Moieties 56:63 Peptide Moieties 48:63 Peptide Moieties 48:63 Cooperative Interactions of Oligosaccharide and Peptide Moieties of a Glycopeptide Derived from IgE with Galectin-9. 26582205 4 71 with digestion 612:620 arg1 trypsin 662:668 trypsin 662:668 trypsin 662:668 Sequential digestion of TIB-141 with lysyl endopeptidase and trypsin resulted in the identification of a glycopeptide (H-Lys13-Try3; 48 amino acid residues) with a single N-linked oligosaccharide near the N terminus capable of neutralizing the effect of galectin-9 and another glycopeptide with two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity. 26582205 4 71 with digestion 612:620 arg1 endopeptidase 644:656 lysyl endopeptidase 638:656 lysyl endopeptidase 638:656 Sequential digestion of TIB-141 with lysyl endopeptidase and trypsin resulted in the identification of a glycopeptide (H-Lys13-Try3; 48 amino acid residues) with a single N-linked oligosaccharide near the N terminus capable of neutralizing the effect of galectin-9 and another glycopeptide with two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity. 26582205 10 72 dep affinity 2009:2016 arg1 the 1997:1999 the 1997:1999 the 1997:1999 Although the oligosaccharides linked to H-Lys13-Try3 could not be fully characterized, these results indicate the possibility that cooperative binding of oligosaccharide and neighboring polypeptide structures of TIB-141 to galectin-9 affects the overall affinity and specificity of the IgE-lectin interaction. 26582205 6 73 theme activity 1241:1248 arg1 loss 1229:1232 loss 1229:1232 loss of the activity 1229:1248 Removal of the C-terminal 38 amino acid residues of H-Lys13-Try3 with glutamyl endopeptidase, however, also resulted in loss of the activity. 26582205 9 74 theme biantennary 1685:1695 arg1 oligosaccharides 1710:1725 biantennary complex type oligosaccharides 1685:1725 biantennary complex type oligosaccharides with a core fucose residue 1685:1752 The structures of the oligosaccharides were consistent with the sugar-binding specificity of galectin-9, whereas the nonbinding fraction contained monosialylated and disialylated biantennary complex type oligosaccharides with a core fucose residue. 26582205 4 75 with glycopeptide 878:889 arg1 residues 955:962 H-Lys13-Try1; 16 amino acid residues 927:962 H-Lys13-Try1; 16 amino acid residues 927:962 Sequential digestion of TIB-141 with lysyl endopeptidase and trypsin resulted in the identification of a glycopeptide (H-Lys13-Try3; 48 amino acid residues) with a single N-linked oligosaccharide near the N terminus capable of neutralizing the effect of galectin-9 and another glycopeptide with two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity. 26582205 4 75 with glycopeptide 878:889 arg1 oligosaccharides 909:924 two N-linked oligosaccharides 896:924 two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity 896:985 Sequential digestion of TIB-141 with lysyl endopeptidase and trypsin resulted in the identification of a glycopeptide (H-Lys13-Try3; 48 amino acid residues) with a single N-linked oligosaccharide near the N terminus capable of neutralizing the effect of galectin-9 and another glycopeptide with two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity. 26582205 8 76 theme bi/tri-antennary 1431:1446 arg1 oligosaccharides 1461:1476 bi/tri-antennary complex type oligosaccharides 1431:1476 bi/tri-antennary complex type oligosaccharides 1431:1476 The galectin-9-binding fraction of pyridylaminated oligosaccharides contained asialo- and monosialylated bi/tri-antennary complex type oligosaccharides with a core fucose residue. 26582205 9 77 theme type 1705:1708 arg1 oligosaccharides 1710:1725 biantennary complex type oligosaccharides 1685:1725 biantennary complex type oligosaccharides with a core fucose residue 1685:1752 The structures of the oligosaccharides were consistent with the sugar-binding specificity of galectin-9, whereas the nonbinding fraction contained monosialylated and disialylated biantennary complex type oligosaccharides with a core fucose residue. 26582205 4 78 theme lower 972:976 arg1 activity 978:985 lower activity 972:985 lower activity 972:985 Sequential digestion of TIB-141 with lysyl endopeptidase and trypsin resulted in the identification of a glycopeptide (H-Lys13-Try3; 48 amino acid residues) with a single N-linked oligosaccharide near the N terminus capable of neutralizing the effect of galectin-9 and another glycopeptide with two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity. 26582205 8 79 theme type 1456:1459 arg1 oligosaccharides 1461:1476 bi/tri-antennary complex type oligosaccharides 1431:1476 bi/tri-antennary complex type oligosaccharides 1431:1476 The galectin-9-binding fraction of pyridylaminated oligosaccharides contained asialo- and monosialylated bi/tri-antennary complex type oligosaccharides with a core fucose residue. 26582205 6 80 theme amino 1138:1142 arg1 H-Lys13-Try3 1161:1172 H-Lys13-Try3 1161:1172 H-Lys13-Try3 1161:1172 Removal of the C-terminal 38 amino acid residues of H-Lys13-Try3 with glutamyl endopeptidase, however, also resulted in loss of the activity. 26582205 6 80 theme amino 1138:1142 arg1 residues 1149:1156 the C-terminal 38 amino acid residues 1120:1156 the C-terminal 38 amino acid residues of H-Lys13-Try3 1120:1172 Removal of the C-terminal 38 amino acid residues of H-Lys13-Try3 with glutamyl endopeptidase, however, also resulted in loss of the activity. 26582205 2 81 theme mouse 420:424 arg1 TIB-141 442:448 TIB-141 442:448 TIB-141 442:448 To elucidate the mechanism of the interaction in detail, we focused on identification and structural analysis of IgE glycans responsible for the galectin-9-induced suppression using mouse monoclonal IgE (TIB-141). 26582205 2 81 theme mouse 420:424 arg1 IgE 437:439 mouse monoclonal IgE 420:439 mouse monoclonal IgE (TIB-141) 420:449 To elucidate the mechanism of the interaction in detail, we focused on identification and structural analysis of IgE glycans responsible for the galectin-9-induced suppression using mouse monoclonal IgE (TIB-141). 26582205 9 82 theme core 1734:1737 arg1 residue 1746:1752 a core fucose residue 1732:1752 a core fucose residue 1732:1752 The structures of the oligosaccharides were consistent with the sugar-binding specificity of galectin-9, whereas the nonbinding fraction contained monosialylated and disialylated biantennary complex type oligosaccharides with a core fucose residue. 26582205 6 83 theme C-terminal 1124:1133 arg1 H-Lys13-Try3 1161:1172 H-Lys13-Try3 1161:1172 H-Lys13-Try3 1161:1172 Removal of the C-terminal 38 amino acid residues of H-Lys13-Try3 with glutamyl endopeptidase, however, also resulted in loss of the activity. 26582205 6 83 theme C-terminal 1124:1133 arg1 residues 1149:1156 the C-terminal 38 amino acid residues 1120:1156 the C-terminal 38 amino acid residues of H-Lys13-Try3 1120:1172 Removal of the C-terminal 38 amino acid residues of H-Lys13-Try3 with glutamyl endopeptidase, however, also resulted in loss of the activity. 26582205 8 84 theme core 1485:1488 arg1 residue 1497:1503 a core fucose residue 1483:1503 a core fucose residue 1483:1503 The galectin-9-binding fraction of pyridylaminated oligosaccharides contained asialo- and monosialylated bi/tri-antennary complex type oligosaccharides with a core fucose residue. 26582205 0 85 theme Oligosaccharide 28:42 arg1 Interactions 12:23 Cooperative Interactions 0:23 Cooperative Interactions of Oligosaccharide and Peptide Moieties of a Glycopeptide 0:81 Cooperative Interactions of Oligosaccharide and Peptide Moieties of a Glycopeptide Derived from IgE with Galectin-9. 26582205 4 86 contain having 965:970 arg1 residues 955:962 H-Lys13-Try1; 16 amino acid residues 927:962 H-Lys13-Try1; 16 amino acid residues 927:962 Sequential digestion of TIB-141 with lysyl endopeptidase and trypsin resulted in the identification of a glycopeptide (H-Lys13-Try3; 48 amino acid residues) with a single N-linked oligosaccharide near the N terminus capable of neutralizing the effect of galectin-9 and another glycopeptide with two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity. 26582205 4 86 contain having 965:970 arg1 oligosaccharides 909:924 two N-linked oligosaccharides 896:924 two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity 896:985 Sequential digestion of TIB-141 with lysyl endopeptidase and trypsin resulted in the identification of a glycopeptide (H-Lys13-Try3; 48 amino acid residues) with a single N-linked oligosaccharide near the N terminus capable of neutralizing the effect of galectin-9 and another glycopeptide with two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity. 26582205 4 86 contain having 965:970 arg2 activity 978:985 lower activity 972:985 lower activity 972:985 Sequential digestion of TIB-141 with lysyl endopeptidase and trypsin resulted in the identification of a glycopeptide (H-Lys13-Try3; 48 amino acid residues) with a single N-linked oligosaccharide near the N terminus capable of neutralizing the effect of galectin-9 and another glycopeptide with two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity. 26582205 4 87 with glycopeptide 706:717 arg1 oligosaccharide 781:795 a single N-linked oligosaccharide 763:795 a single N-linked oligosaccharide near the N terminus capable of neutralizing the effect of galectin-9 and another glycopeptide with two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity 763:985 Sequential digestion of TIB-141 with lysyl endopeptidase and trypsin resulted in the identification of a glycopeptide (H-Lys13-Try3; 48 amino acid residues) with a single N-linked oligosaccharide near the N terminus capable of neutralizing the effect of galectin-9 and another glycopeptide with two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity. 26582205 4 88 theme single 765:770 arg1 oligosaccharide 781:795 a single N-linked oligosaccharide 763:795 a single N-linked oligosaccharide near the N terminus capable of neutralizing the effect of galectin-9 and another glycopeptide with two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity 763:985 Sequential digestion of TIB-141 with lysyl endopeptidase and trypsin resulted in the identification of a glycopeptide (H-Lys13-Try3; 48 amino acid residues) with a single N-linked oligosaccharide near the N terminus capable of neutralizing the effect of galectin-9 and another glycopeptide with two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity. 26582205 7 89 theme H-Lys13-Try1 1312:1323 arg1 oligosaccharides 1292:1307 N-linked oligosaccharides 1283:1307 N-linked oligosaccharides of H-Lys13-Try1 1283:1323 We determined the structures of N-linked oligosaccharides of H-Lys13-Try1. 26582205 0 90 theme Peptide 48:54 arg1 Moieties 56:63 Peptide Moieties 48:63 Peptide Moieties 48:63 Cooperative Interactions of Oligosaccharide and Peptide Moieties of a Glycopeptide Derived from IgE with Galectin-9. 26582205 1 91 with interaction 216:226 arg1 IgE 233:235 IgE 233:235 IgE 233:235 We previously showed that galectin-9 suppresses degranulation of mast cells through protein-glycan interaction with IgE. 26582205 2 92 from interaction 272:282 arg1 detail 287:292 detail 287:292 detail 287:292 To elucidate the mechanism of the interaction in detail, we focused on identification and structural analysis of IgE glycans responsible for the galectin-9-induced suppression using mouse monoclonal IgE (TIB-141). 26582205 9 93 with consistent 1550:1559 arg1 specificity 1584:1594 the sugar-binding specificity 1566:1594 the sugar-binding specificity of galectin-9 1566:1608 The structures of the oligosaccharides were consistent with the sugar-binding specificity of galectin-9, whereas the nonbinding fraction contained monosialylated and disialylated biantennary complex type oligosaccharides with a core fucose residue. 26582205 3 94 theme cells 525:529 arg1 degranulation 500:512 degranulation 500:512 degranulation 500:512 TIB-141 in combination with the antigen induced degranulation of RBL-2H3 cells, which was almost completely inhibited by human and mouse galectin-9. 26582205 5 95 theme chain 1033:1037 arg1 elimination 998:1008 Enzymatic elimination 988:1008 Enzymatic elimination of the oligosaccharide chain from H-Lys13-Try3 and H-Lys13-Try1 988:1072 Enzymatic elimination of the oligosaccharide chain from H-Lys13-Try3 and H-Lys13-Try1 completely abolished the activity. 26582205 6 96 theme glutamyl 1179:1186 arg1 endopeptidase 1188:1200 glutamyl endopeptidase 1179:1200 glutamyl endopeptidase 1179:1200 Removal of the C-terminal 38 amino acid residues of H-Lys13-Try3 with glutamyl endopeptidase, however, also resulted in loss of the activity. 26582205 4 97 theme lysyl 638:642 arg1 endopeptidase 644:656 lysyl endopeptidase 638:656 lysyl endopeptidase 638:656 Sequential digestion of TIB-141 with lysyl endopeptidase and trypsin resulted in the identification of a glycopeptide (H-Lys13-Try3; 48 amino acid residues) with a single N-linked oligosaccharide near the N terminus capable of neutralizing the effect of galectin-9 and another glycopeptide with two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity. 26582205 6 98 with Removal 1109:1115 arg1 endopeptidase 1188:1200 glutamyl endopeptidase 1179:1200 glutamyl endopeptidase 1179:1200 Removal of the C-terminal 38 amino acid residues of H-Lys13-Try3 with glutamyl endopeptidase, however, also resulted in loss of the activity. 26582205 4 99 link N-linked 772:779 arg1 oligosaccharide 781:795 a single N-linked oligosaccharide 763:795 a single N-linked oligosaccharide near the N terminus capable of neutralizing the effect of galectin-9 and another glycopeptide with two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity 763:985 Sequential digestion of TIB-141 with lysyl endopeptidase and trypsin resulted in the identification of a glycopeptide (H-Lys13-Try3; 48 amino acid residues) with a single N-linked oligosaccharide near the N terminus capable of neutralizing the effect of galectin-9 and another glycopeptide with two N-linked oligosaccharides (H-Lys13-Try1; 16 amino acid residues) having lower activity. 24514897 10 0 theme steps 1980:1984 arg1 days 1990:1993 >20 steps 4-5 days 1976:1993 >20 steps 4-5 days 1976:1993 Using two D2 dopamine receptor cellular models (i.e. CHO-D2L and HEK-AC6/D2L), we have converted our 48-well sensitization assay (>20 steps 4-5 days) to a five-step, single day assay in 384-well format. 24514897 10 0 theme steps 1980:1984 arg1 assay 1969:1973 our 48-well sensitization assay 1943:1973 our 48-well sensitization assay (>20 steps 4-5 days) 1943:1994 Using two D2 dopamine receptor cellular models (i.e. CHO-D2L and HEK-AC6/D2L), we have converted our 48-well sensitization assay (>20 steps 4-5 days) to a five-step, single day assay in 384-well format. 24514897 9 1 theme high 1760:1763 arg1 HTS 1787:1789 HTS 1787:1789 HTS 1787:1789 Thus, the development of a robust cell-based assay that can be used for high throughput screening (HTS) in a 384 well format would facilitate future studies. 24514897 9 1 theme high 1760:1763 arg1 screening 1776:1784 high throughput screening 1760:1784 high throughput screening (HTS) 1760:1790 Thus, the development of a robust cell-based assay that can be used for high throughput screening (HTS) in a 384 well format would facilitate future studies. 24514897 3 2 link Gαi/o-linked 689:700 arg1 receptors 702:710 Gαi/o-linked receptors 689:710 Gαi/o-linked receptors 689:710 Previous studies have demonstrated that this enhancement of AC responsiveness is observed both in vitro and in vivo following the chronic activation of several types of Gαi/o-linked receptors including D2 dopamine and μ opioid receptors. 24514897 10 3 theme five-step 2001:2009 arg1 assay 2023:2027 a five-step, single day assay 1999:2027 assay 2023:2027 Using two D2 dopamine receptor cellular models (i.e. CHO-D2L and HEK-AC6/D2L), we have converted our 48-well sensitization assay (>20 steps 4-5 days) to a five-step, single day assay in 384-well format. 24514897 6 4 theme heterologous 1243:1254 arg1 sensitization 1256:1268 the heterologous sensitization 1239:1268 the heterologous sensitization of AC 1239:1274 Previous studies have implicated kinase and Gbγ signaling as overlapping components that regulate the heterologous sensitization of AC. 24514897 3 5 theme AC 580:581 arg1 responsiveness 583:596 AC responsiveness 580:596 AC responsiveness 580:596 Previous studies have demonstrated that this enhancement of AC responsiveness is observed both in vitro and in vivo following the chronic activation of several types of Gαi/o-linked receptors including D2 dopamine and μ opioid receptors. 24514897 1 6 theme signaling 179:187 arg1 Sensitization 140:152 Sensitization 140:152 Sensitization of adenylyl cyclase (AC) signaling 140:187 Sensitization of adenylyl cyclase (AC) signaling has been implicated in a variety of neuropsychiatric and neurologic disorders including substance abuse and Parkinson's disease. 24514897 9 7 used used 1751:1754 arg2 assay 1733:1737 a robust cell-based assay 1713:1737 a robust cell-based assay that can be used for high throughput screening (HTS) in a 384 well format 1713:1811 Thus, the development of a robust cell-based assay that can be used for high throughput screening (HTS) in a 384 well format would facilitate future studies. 24514897 11 8 theme molecule 2086:2093 arg1 screening 2095:2103 small molecule screening 2080:2103 small molecule screening 2080:2103 This new format is amenable to small molecule screening, and we demonstrate that this assay design can also be readily used for reverse transfection of siRNA in anticipation of targeted siRNA library screening. 24514897 10 9 theme single 2012:2017 arg1 assay 2023:2027 a five-step, single day assay 1999:2027 assay 2023:2027 Using two D2 dopamine receptor cellular models (i.e. CHO-D2L and HEK-AC6/D2L), we have converted our 48-well sensitization assay (>20 steps 4-5 days) to a five-step, single day assay in 384-well format. 24514897 10 10 theme D2 1856:1857 arg1 receptor 1868:1875 D2 dopamine receptor 1856:1875 D2 dopamine receptor 1856:1875 Using two D2 dopamine receptor cellular models (i.e. CHO-D2L and HEK-AC6/D2L), we have converted our 48-well sensitization assay (>20 steps 4-5 days) to a five-step, single day assay in 384-well format. 24514897 9 11 theme 384 1797:1799 arg1 format 1806:1811 a 384 well format 1795:1811 a 384 well format 1795:1811 Thus, the development of a robust cell-based assay that can be used for high throughput screening (HTS) in a 384 well format would facilitate future studies. 24514897 8 12 theme continuous 1552:1561 arg1 maintenance 1576:1586 continuous cell culture maintenance 1552:1586 continuous cell culture maintenance as well as a complex methodology for measuring cAMP accumulation that involves multiple wash steps 1552:1685 Previous approaches to study sensitization are generally cumbersome involving continuous cell culture maintenance as well as a complex methodology for measuring cAMP accumulation that involves multiple wash steps. 24514897 10 13 dep CHO-D2L 1899:1905 arg1 i.e. 1894:1897 i.e. 1894:1897 i.e. 1894:1897 Using two D2 dopamine receptor cellular models (i.e. CHO-D2L and HEK-AC6/D2L), we have converted our 48-well sensitization assay (>20 steps 4-5 days) to a five-step, single day assay in 384-well format. 24514897 8 14 theme culture 1568:1574 arg1 maintenance 1576:1586 continuous cell culture maintenance 1552:1586 continuous cell culture maintenance as well as a complex methodology for measuring cAMP accumulation that involves multiple wash steps 1552:1685 Previous approaches to study sensitization are generally cumbersome involving continuous cell culture maintenance as well as a complex methodology for measuring cAMP accumulation that involves multiple wash steps. 24514897 7 15 theme greater 1454:1460 arg1 throughput 1462:1471 greater throughput 1454:1471 greater throughput 1454:1471 To identify unique and additional overlapping targets associated with sensitization of AC, the development and validation of a scalable cAMP sensitization assay is required for greater throughput. 24514897 10 16 theme >20 1976:1978 arg1 days 1990:1993 >20 steps 4-5 days 1976:1993 >20 steps 4-5 days 1976:1993 Using two D2 dopamine receptor cellular models (i.e. CHO-D2L and HEK-AC6/D2L), we have converted our 48-well sensitization assay (>20 steps 4-5 days) to a five-step, single day assay in 384-well format. 24514897 10 16 theme >20 1976:1978 arg1 assay 1969:1973 our 48-well sensitization assay 1943:1973 our 48-well sensitization assay (>20 steps 4-5 days) 1943:1994 Using two D2 dopamine receptor cellular models (i.e. CHO-D2L and HEK-AC6/D2L), we have converted our 48-well sensitization assay (>20 steps 4-5 days) to a five-step, single day assay in 384-well format. 24514897 10 17 theme 384-well 2032:2039 arg1 format 2041:2046 384-well format 2032:2046 384-well format 2032:2046 Using two D2 dopamine receptor cellular models (i.e. CHO-D2L and HEK-AC6/D2L), we have converted our 48-well sensitization assay (>20 steps 4-5 days) to a five-step, single day assay in 384-well format. 24514897 5 18 theme heterologous 1107:1118 arg1 sensitization 1120:1132 heterologous sensitization 1107:1132 heterologous sensitization of AC 1107:1138 The lack of mechanistic data presumably reflects the complexity involved with this adaptive response, suggesting that nonbiased approaches could aid in identifying the molecular pathways involved in heterologous sensitization of AC. 24514897 7 19 theme assay 1432:1436 arg1 validation 1388:1397 validation 1388:1397 validation 1388:1397 To identify unique and additional overlapping targets associated with sensitization of AC, the development and validation of a scalable cAMP sensitization assay is required for greater throughput. 24514897 7 19 theme assay 1432:1436 arg1 development 1372:1382 development 1372:1382 development 1372:1382 To identify unique and additional overlapping targets associated with sensitization of AC, the development and validation of a scalable cAMP sensitization assay is required for greater throughput. 24514897 1 20 theme cyclase 166:172 arg1 signaling 179:187 adenylyl cyclase (AC) signaling 157:187 adenylyl cyclase (AC) signaling 157:187 Sensitization of adenylyl cyclase (AC) signaling has been implicated in a variety of neuropsychiatric and neurologic disorders including substance abuse and Parkinson's disease. 24514897 7 21 theme overlapping 1311:1321 arg1 targets 1323:1329 unique and additional overlapping targets 1289:1329 unique and additional overlapping targets associated with sensitization of AC 1289:1365 To identify unique and additional overlapping targets associated with sensitization of AC, the development and validation of a scalable cAMP sensitization assay is required for greater throughput. 24514897 3 22 theme chronic 650:656 arg1 activation 658:667 the chronic activation 646:667 the chronic activation of several types of Gαi/o-linked receptors including D2 dopamine and μ opioid receptors 646:755 Previous studies have demonstrated that this enhancement of AC responsiveness is observed both in vitro and in vivo following the chronic activation of several types of Gαi/o-linked receptors including D2 dopamine and μ opioid receptors. 24514897 5 23 theme mechanistic 920:930 arg1 data 932:935 mechanistic data 920:935 mechanistic data 920:935 The lack of mechanistic data presumably reflects the complexity involved with this adaptive response, suggesting that nonbiased approaches could aid in identifying the molecular pathways involved in heterologous sensitization of AC. 24514897 11 24 theme library 2241:2247 arg1 screening 2249:2257 targeted siRNA library screening 2226:2257 targeted siRNA library screening 2226:2257 This new format is amenable to small molecule screening, and we demonstrate that this assay design can also be readily used for reverse transfection of siRNA in anticipation of targeted siRNA library screening. 24514897 8 25 theme complex 1601:1607 arg1 methodology 1609:1619 a complex methodology 1599:1619 continuous cell culture maintenance as well as a complex methodology for measuring cAMP accumulation that involves multiple wash steps 1552:1685 Previous approaches to study sensitization are generally cumbersome involving continuous cell culture maintenance as well as a complex methodology for measuring cAMP accumulation that involves multiple wash steps. 24514897 11 26 from transfection 2185:2196 arg1 anticipation 2210:2221 anticipation 2210:2221 anticipation of targeted siRNA library screening 2210:2257 This new format is amenable to small molecule screening, and we demonstrate that this assay design can also be readily used for reverse transfection of siRNA in anticipation of targeted siRNA library screening. 24514897 7 27 theme unique 1289:1294 arg1 targets 1323:1329 unique and additional overlapping targets 1289:1329 unique and additional overlapping targets associated with sensitization of AC 1289:1365 To identify unique and additional overlapping targets associated with sensitization of AC, the development and validation of a scalable cAMP sensitization assay is required for greater throughput. 24514897 8 28 theme cAMP 1635:1638 arg1 accumulation 1640:1651 cAMP accumulation 1635:1651 cAMP accumulation that involves multiple wash steps 1635:1685 Previous approaches to study sensitization are generally cumbersome involving continuous cell culture maintenance as well as a complex methodology for measuring cAMP accumulation that involves multiple wash steps. 24514897 2 29 theme receptors 422:430 arg1 activation 402:411 persistent activation 391:411 persistent activation of these receptors 391:430 Acute activation of Gαi/o-linked receptors inhibits AC activity, whereas persistent activation of these receptors results in heterologous sensitization of AC and increased levels of intracellular cAMP. 24514897 0 30 theme siRNA 110:114 arg1 applications 126:137 siRNA screening applications 110:137 siRNA screening applications 110:137 Drug-induced sensitization of adenylyl cyclase: assay streamlining and miniaturization for small molecule and siRNA screening applications. 24514897 11 31 theme targeted 2226:2233 arg1 screening 2249:2257 targeted siRNA library screening 2226:2257 targeted siRNA library screening 2226:2257 This new format is amenable to small molecule screening, and we demonstrate that this assay design can also be readily used for reverse transfection of siRNA in anticipation of targeted siRNA library screening. 24514897 5 32 theme nonbiased 1026:1034 arg1 approaches 1036:1045 nonbiased approaches 1026:1045 nonbiased approaches 1026:1045 The lack of mechanistic data presumably reflects the complexity involved with this adaptive response, suggesting that nonbiased approaches could aid in identifying the molecular pathways involved in heterologous sensitization of AC. 24514897 7 33 theme sensitization 1418:1430 arg1 assay 1432:1436 a scalable cAMP sensitization assay 1402:1436 a scalable cAMP sensitization assay 1402:1436 To identify unique and additional overlapping targets associated with sensitization of AC, the development and validation of a scalable cAMP sensitization assay is required for greater throughput. 24514897 2 34 theme increased 480:488 arg1 levels 490:495 increased levels 480:495 increased levels of intracellular cAMP 480:517 Acute activation of Gαi/o-linked receptors inhibits AC activity, whereas persistent activation of these receptors results in heterologous sensitization of AC and increased levels of intracellular cAMP. 24514897 4 35 theme AC 797:798 arg1 sensitization 780:792 heterologous sensitization 767:792 heterologous sensitization of AC 767:798 Although heterologous sensitization of AC was first reported four decades ago, the mechanism(s) that underlie this phenomenon remain largely unknown. 24514897 0 36 theme Drug-induced 0:11 arg1 sensitization 13:25 Drug-induced sensitization 0:25 Drug-induced sensitization of adenylyl cyclase: assay streamlining and miniaturization for small molecule and siRNA screening applications. 0:138 Drug-induced sensitization of adenylyl cyclase: assay streamlining and miniaturization for small molecule and siRNA screening applications. 24514897 7 37 theme scalable 1404:1411 arg1 assay 1432:1436 a scalable cAMP sensitization assay 1402:1436 a scalable cAMP sensitization assay 1402:1436 To identify unique and additional overlapping targets associated with sensitization of AC, the development and validation of a scalable cAMP sensitization assay is required for greater throughput. 24514897 2 38 theme AC 473:474 arg1 levels 490:495 increased levels 480:495 increased levels of intracellular cAMP 480:517 Acute activation of Gαi/o-linked receptors inhibits AC activity, whereas persistent activation of these receptors results in heterologous sensitization of AC and increased levels of intracellular cAMP. 24514897 2 38 theme AC 473:474 arg1 sensitization 456:468 heterologous sensitization 443:468 heterologous sensitization of AC 443:474 Acute activation of Gαi/o-linked receptors inhibits AC activity, whereas persistent activation of these receptors results in heterologous sensitization of AC and increased levels of intracellular cAMP. 24514897 8 39 theme multiple 1667:1674 arg1 steps 1681:1685 multiple wash steps 1667:1685 multiple wash steps 1667:1685 Previous approaches to study sensitization are generally cumbersome involving continuous cell culture maintenance as well as a complex methodology for measuring cAMP accumulation that involves multiple wash steps. 24514897 8 40 theme Previous 1474:1481 arg1 approaches 1483:1492 Previous approaches 1474:1492 Previous approaches to study sensitization 1474:1515 Previous approaches to study sensitization are generally cumbersome involving continuous cell culture maintenance as well as a complex methodology for measuring cAMP accumulation that involves multiple wash steps. 24514897 2 41 theme cAMP 514:517 arg1 levels 490:495 increased levels 480:495 increased levels of intracellular cAMP 480:517 Acute activation of Gαi/o-linked receptors inhibits AC activity, whereas persistent activation of these receptors results in heterologous sensitization of AC and increased levels of intracellular cAMP. 24514897 2 41 theme cAMP 514:517 arg1 sensitization 456:468 heterologous sensitization 443:468 heterologous sensitization of AC 443:474 Acute activation of Gαi/o-linked receptors inhibits AC activity, whereas persistent activation of these receptors results in heterologous sensitization of AC and increased levels of intracellular cAMP. 24514897 3 42 theme Gαi/o-linked 689:700 arg1 receptors 702:710 Gαi/o-linked receptors 689:710 Gαi/o-linked receptors 689:710 Previous studies have demonstrated that this enhancement of AC responsiveness is observed both in vitro and in vivo following the chronic activation of several types of Gαi/o-linked receptors including D2 dopamine and μ opioid receptors. 24514897 0 43 theme cyclase 39:45 arg1 sensitization 13:25 Drug-induced sensitization 0:25 Drug-induced sensitization of adenylyl cyclase: assay streamlining and miniaturization for small molecule and siRNA screening applications. 0:138 Drug-induced sensitization of adenylyl cyclase: assay streamlining and miniaturization for small molecule and siRNA screening applications. 24514897 11 44 theme siRNA 2235:2239 arg1 screening 2249:2257 targeted siRNA library screening 2226:2257 targeted siRNA library screening 2226:2257 This new format is amenable to small molecule screening, and we demonstrate that this assay design can also be readily used for reverse transfection of siRNA in anticipation of targeted siRNA library screening. 24514897 0 45 dep assay 48:52 arg1 streamlining 54:65 streamlining 54:65 streamlining 54:65 Drug-induced sensitization of adenylyl cyclase: assay streamlining and miniaturization for small molecule and siRNA screening applications. 24514897 3 46 theme types 680:684 arg1 activation 658:667 the chronic activation 646:667 the chronic activation of several types of Gαi/o-linked receptors including D2 dopamine and μ opioid receptors 646:755 Previous studies have demonstrated that this enhancement of AC responsiveness is observed both in vitro and in vivo following the chronic activation of several types of Gαi/o-linked receptors including D2 dopamine and μ opioid receptors. 24514897 2 47 theme AC 370:371 arg1 activity 373:380 AC activity 370:380 AC activity 370:380 Acute activation of Gαi/o-linked receptors inhibits AC activity, whereas persistent activation of these receptors results in heterologous sensitization of AC and increased levels of intracellular cAMP. 24514897 9 48 theme cell-based 1722:1731 arg1 assay 1733:1737 a robust cell-based assay 1713:1737 a robust cell-based assay that can be used for high throughput screening (HTS) in a 384 well format 1713:1811 Thus, the development of a robust cell-based assay that can be used for high throughput screening (HTS) in a 384 well format would facilitate future studies. 24514897 2 49 theme receptors 351:359 arg1 activation 324:333 Acute activation 318:333 Acute activation of Gαi/o-linked receptors 318:359 Acute activation of Gαi/o-linked receptors inhibits AC activity, whereas persistent activation of these receptors results in heterologous sensitization of AC and increased levels of intracellular cAMP. 24514897 11 50 theme new 2054:2056 arg1 format 2058:2063 This new format 2049:2063 This new format 2049:2063 This new format is amenable to small molecule screening, and we demonstrate that this assay design can also be readily used for reverse transfection of siRNA in anticipation of targeted siRNA library screening. 24514897 7 51 theme AC 1364:1365 arg1 sensitization 1347:1359 sensitization 1347:1359 sensitization of AC 1347:1365 To identify unique and additional overlapping targets associated with sensitization of AC, the development and validation of a scalable cAMP sensitization assay is required for greater throughput. 24514897 10 52 theme 48-well 1947:1953 arg1 days 1990:1993 >20 steps 4-5 days 1976:1993 >20 steps 4-5 days 1976:1993 Using two D2 dopamine receptor cellular models (i.e. CHO-D2L and HEK-AC6/D2L), we have converted our 48-well sensitization assay (>20 steps 4-5 days) to a five-step, single day assay in 384-well format. 24514897 10 52 theme 48-well 1947:1953 arg1 assay 1969:1973 our 48-well sensitization assay 1943:1973 our 48-well sensitization assay (>20 steps 4-5 days) 1943:1994 Using two D2 dopamine receptor cellular models (i.e. CHO-D2L and HEK-AC6/D2L), we have converted our 48-well sensitization assay (>20 steps 4-5 days) to a five-step, single day assay in 384-well format. 24514897 2 53 theme persistent 391:400 arg1 activation 402:411 persistent activation 391:411 persistent activation of these receptors 391:430 Acute activation of Gαi/o-linked receptors inhibits AC activity, whereas persistent activation of these receptors results in heterologous sensitization of AC and increased levels of intracellular cAMP. 24514897 2 54 link Gαi/o-linked 338:349 arg1 receptors 351:359 Gαi/o-linked receptors 338:359 Gαi/o-linked receptors 338:359 Acute activation of Gαi/o-linked receptors inhibits AC activity, whereas persistent activation of these receptors results in heterologous sensitization of AC and increased levels of intracellular cAMP. 24514897 1 55 theme disorders 257:265 arg1 disease 309:315 Parkinson's disease 297:315 Parkinson's disease 297:315 Sensitization of adenylyl cyclase (AC) signaling has been implicated in a variety of neuropsychiatric and neurologic disorders including substance abuse and Parkinson's disease. 24514897 1 55 theme disorders 257:265 arg1 abuse 287:291 substance abuse 277:291 substance abuse 277:291 Sensitization of adenylyl cyclase (AC) signaling has been implicated in a variety of neuropsychiatric and neurologic disorders including substance abuse and Parkinson's disease. 24514897 1 55 theme disorders 257:265 arg1 disorders 257:265 neuropsychiatric and neurologic disorders 225:265 neuropsychiatric and neurologic disorders including substance abuse and Parkinson's disease 225:315 Sensitization of adenylyl cyclase (AC) signaling has been implicated in a variety of neuropsychiatric and neurologic disorders including substance abuse and Parkinson's disease. 24514897 1 55 theme disorders 257:265 arg1 variety 214:220 a variety 212:220 a variety of neuropsychiatric and neurologic disorders including substance abuse and Parkinson's disease 212:315 Sensitization of adenylyl cyclase (AC) signaling has been implicated in a variety of neuropsychiatric and neurologic disorders including substance abuse and Parkinson's disease. 24514897 3 56 theme μ 738:738 arg1 receptors 747:755 μ opioid receptors 738:755 μ opioid receptors 738:755 Previous studies have demonstrated that this enhancement of AC responsiveness is observed both in vitro and in vivo following the chronic activation of several types of Gαi/o-linked receptors including D2 dopamine and μ opioid receptors. 24514897 9 57 theme robust 1715:1720 arg1 assay 1733:1737 a robust cell-based assay 1713:1737 a robust cell-based assay that can be used for high throughput screening (HTS) in a 384 well format 1713:1811 Thus, the development of a robust cell-based assay that can be used for high throughput screening (HTS) in a 384 well format would facilitate future studies. 24514897 3 58 theme responsiveness 583:596 arg1 enhancement 565:575 this enhancement 560:575 this enhancement of AC responsiveness 560:596 Previous studies have demonstrated that this enhancement of AC responsiveness is observed both in vitro and in vivo following the chronic activation of several types of Gαi/o-linked receptors including D2 dopamine and μ opioid receptors. 24514897 1 59 theme substance 277:285 arg1 abuse 287:291 substance abuse 277:291 substance abuse 277:291 Sensitization of adenylyl cyclase (AC) signaling has been implicated in a variety of neuropsychiatric and neurologic disorders including substance abuse and Parkinson's disease. 24514897 11 60 theme small 2080:2084 arg1 screening 2095:2103 small molecule screening 2080:2103 small molecule screening 2080:2103 This new format is amenable to small molecule screening, and we demonstrate that this assay design can also be readily used for reverse transfection of siRNA in anticipation of targeted siRNA library screening. 24514897 9 61 theme throughput 1765:1774 arg1 HTS 1787:1789 HTS 1787:1789 HTS 1787:1789 Thus, the development of a robust cell-based assay that can be used for high throughput screening (HTS) in a 384 well format would facilitate future studies. 24514897 9 61 theme throughput 1765:1774 arg1 screening 1776:1784 high throughput screening 1760:1784 high throughput screening (HTS) 1760:1790 Thus, the development of a robust cell-based assay that can be used for high throughput screening (HTS) in a 384 well format would facilitate future studies. 24514897 11 62 theme reverse 2177:2183 arg1 transfection 2185:2196 reverse transfection 2177:2196 reverse transfection of siRNA in anticipation of targeted siRNA library screening 2177:2257 This new format is amenable to small molecule screening, and we demonstrate that this assay design can also be readily used for reverse transfection of siRNA in anticipation of targeted siRNA library screening. 24514897 10 63 theme cellular 1877:1884 arg1 HEK-AC6/D2L 1911:1921 HEK-AC6/D2L 1911:1921 HEK-AC6/D2L 1911:1921 Using two D2 dopamine receptor cellular models (i.e. CHO-D2L and HEK-AC6/D2L), we have converted our 48-well sensitization assay (>20 steps 4-5 days) to a five-step, single day assay in 384-well format. 24514897 10 63 theme cellular 1877:1884 arg1 models 1886:1891 two D2 dopamine receptor cellular models 1852:1891 two D2 dopamine receptor cellular models (i.e. CHO-D2L and HEK-AC6/D2L) 1852:1922 Using two D2 dopamine receptor cellular models (i.e. CHO-D2L and HEK-AC6/D2L), we have converted our 48-well sensitization assay (>20 steps 4-5 days) to a five-step, single day assay in 384-well format. 24514897 10 63 theme cellular 1877:1884 arg1 CHO-D2L 1899:1905 CHO-D2L 1899:1905 CHO-D2L 1899:1905 Using two D2 dopamine receptor cellular models (i.e. CHO-D2L and HEK-AC6/D2L), we have converted our 48-well sensitization assay (>20 steps 4-5 days) to a five-step, single day assay in 384-well format. 24514897 10 64 theme day 2019:2021 arg1 assay 2023:2027 a five-step, single day assay 1999:2027 assay 2023:2027 Using two D2 dopamine receptor cellular models (i.e. CHO-D2L and HEK-AC6/D2L), we have converted our 48-well sensitization assay (>20 steps 4-5 days) to a five-step, single day assay in 384-well format. 24514897 2 65 theme Acute 318:322 arg1 activation 324:333 Acute activation 318:333 Acute activation of Gαi/o-linked receptors 318:359 Acute activation of Gαi/o-linked receptors inhibits AC activity, whereas persistent activation of these receptors results in heterologous sensitization of AC and increased levels of intracellular cAMP. 24514897 8 66 theme cell 1563:1566 arg1 maintenance 1576:1586 continuous cell culture maintenance 1552:1586 continuous cell culture maintenance as well as a complex methodology for measuring cAMP accumulation that involves multiple wash steps 1552:1685 Previous approaches to study sensitization are generally cumbersome involving continuous cell culture maintenance as well as a complex methodology for measuring cAMP accumulation that involves multiple wash steps. 24514897 6 67 theme overlapping 1202:1212 arg1 signaling 1189:1197 kinase and Gbγ signaling 1174:1197 kinase and Gbγ signaling 1174:1197 Previous studies have implicated kinase and Gbγ signaling as overlapping components that regulate the heterologous sensitization of AC. 24514897 6 67 theme overlapping 1202:1212 arg1 components 1214:1223 overlapping components 1202:1223 overlapping components that regulate the heterologous sensitization of AC 1202:1274 Previous studies have implicated kinase and Gbγ signaling as overlapping components that regulate the heterologous sensitization of AC. 24514897 10 68 dep models 1886:1891 arg1 HEK-AC6/D2L 1911:1921 HEK-AC6/D2L 1911:1921 HEK-AC6/D2L 1911:1921 Using two D2 dopamine receptor cellular models (i.e. CHO-D2L and HEK-AC6/D2L), we have converted our 48-well sensitization assay (>20 steps 4-5 days) to a five-step, single day assay in 384-well format. 24514897 10 68 dep models 1886:1891 arg1 models 1886:1891 two D2 dopamine receptor cellular models 1852:1891 two D2 dopamine receptor cellular models (i.e. CHO-D2L and HEK-AC6/D2L) 1852:1922 Using two D2 dopamine receptor cellular models (i.e. CHO-D2L and HEK-AC6/D2L), we have converted our 48-well sensitization assay (>20 steps 4-5 days) to a five-step, single day assay in 384-well format. 24514897 10 68 dep models 1886:1891 arg1 CHO-D2L 1899:1905 CHO-D2L 1899:1905 CHO-D2L 1899:1905 Using two D2 dopamine receptor cellular models (i.e. CHO-D2L and HEK-AC6/D2L), we have converted our 48-well sensitization assay (>20 steps 4-5 days) to a five-step, single day assay in 384-well format. 24514897 5 69 theme AC 1137:1138 arg1 sensitization 1120:1132 heterologous sensitization 1107:1132 heterologous sensitization of AC 1107:1138 The lack of mechanistic data presumably reflects the complexity involved with this adaptive response, suggesting that nonbiased approaches could aid in identifying the molecular pathways involved in heterologous sensitization of AC. 24514897 9 70 theme well 1801:1804 arg1 format 1806:1811 a 384 well format 1795:1811 a 384 well format 1795:1811 Thus, the development of a robust cell-based assay that can be used for high throughput screening (HTS) in a 384 well format would facilitate future studies. 24514897 11 71 theme assay 2135:2139 arg1 design 2141:2146 this assay design 2130:2146 this assay design 2130:2146 This new format is amenable to small molecule screening, and we demonstrate that this assay design can also be readily used for reverse transfection of siRNA in anticipation of targeted siRNA library screening. 24514897 7 72 dep development 1372:1382 arg1 the 1368:1370 the 1368:1370 the 1368:1370 To identify unique and additional overlapping targets associated with sensitization of AC, the development and validation of a scalable cAMP sensitization assay is required for greater throughput. 24514897 10 73 theme dopamine 1859:1866 arg1 receptor 1868:1875 D2 dopamine receptor 1856:1875 D2 dopamine receptor 1856:1875 Using two D2 dopamine receptor cellular models (i.e. CHO-D2L and HEK-AC6/D2L), we have converted our 48-well sensitization assay (>20 steps 4-5 days) to a five-step, single day assay in 384-well format. 24514897 9 74 theme future 1830:1835 arg1 studies 1837:1843 future studies 1830:1843 future studies 1830:1843 Thus, the development of a robust cell-based assay that can be used for high throughput screening (HTS) in a 384 well format would facilitate future studies. 24514897 4 75 theme heterologous 767:778 arg1 sensitization 780:792 heterologous sensitization 767:792 heterologous sensitization of AC 767:798 Although heterologous sensitization of AC was first reported four decades ago, the mechanism(s) that underlie this phenomenon remain largely unknown. 24514897 7 76 theme additional 1300:1309 arg1 targets 1323:1329 unique and additional overlapping targets 1289:1329 unique and additional overlapping targets associated with sensitization of AC 1289:1365 To identify unique and additional overlapping targets associated with sensitization of AC, the development and validation of a scalable cAMP sensitization assay is required for greater throughput. 24514897 1 77 theme adenylyl 157:164 arg1 cyclase 166:172 adenylyl cyclase 157:172 adenylyl cyclase (AC) signaling 157:187 Sensitization of adenylyl cyclase (AC) signaling has been implicated in a variety of neuropsychiatric and neurologic disorders including substance abuse and Parkinson's disease. 24514897 1 77 theme adenylyl 157:164 arg1 AC 175:176 AC 175:176 AC 175:176 Sensitization of adenylyl cyclase (AC) signaling has been implicated in a variety of neuropsychiatric and neurologic disorders including substance abuse and Parkinson's disease. 24514897 6 78 theme AC 1273:1274 arg1 sensitization 1256:1268 the heterologous sensitization 1239:1268 the heterologous sensitization of AC 1239:1274 Previous studies have implicated kinase and Gbγ signaling as overlapping components that regulate the heterologous sensitization of AC. 24514897 0 79 theme small 91:95 arg1 molecule 97:104 small molecule 91:104 small molecule 91:104 Drug-induced sensitization of adenylyl cyclase: assay streamlining and miniaturization for small molecule and siRNA screening applications. 24514897 5 80 theme data 932:935 arg1 lack 912:915 The lack 908:915 The lack of mechanistic data 908:935 The lack of mechanistic data presumably reflects the complexity involved with this adaptive response, suggesting that nonbiased approaches could aid in identifying the molecular pathways involved in heterologous sensitization of AC. 24514897 11 81 theme screening 2249:2257 arg1 anticipation 2210:2221 anticipation 2210:2221 anticipation of targeted siRNA library screening 2210:2257 This new format is amenable to small molecule screening, and we demonstrate that this assay design can also be readily used for reverse transfection of siRNA in anticipation of targeted siRNA library screening. 24514897 3 82 theme receptors 702:710 arg1 receptors 747:755 μ opioid receptors 738:755 μ opioid receptors 738:755 Previous studies have demonstrated that this enhancement of AC responsiveness is observed both in vitro and in vivo following the chronic activation of several types of Gαi/o-linked receptors including D2 dopamine and μ opioid receptors. 24514897 3 82 theme receptors 702:710 arg1 types 680:684 several types 672:684 several types of Gαi/o-linked receptors including D2 dopamine and μ opioid receptors 672:755 Previous studies have demonstrated that this enhancement of AC responsiveness is observed both in vitro and in vivo following the chronic activation of several types of Gαi/o-linked receptors including D2 dopamine and μ opioid receptors. 24514897 3 82 theme receptors 702:710 arg1 dopamine 725:732 D2 dopamine 722:732 D2 dopamine 722:732 Previous studies have demonstrated that this enhancement of AC responsiveness is observed both in vitro and in vivo following the chronic activation of several types of Gαi/o-linked receptors including D2 dopamine and μ opioid receptors. 24514897 7 83 theme cAMP 1413:1416 arg1 assay 1432:1436 a scalable cAMP sensitization assay 1402:1436 a scalable cAMP sensitization assay 1402:1436 To identify unique and additional overlapping targets associated with sensitization of AC, the development and validation of a scalable cAMP sensitization assay is required for greater throughput. 24514897 10 84 from assay 2023:2027 arg1 format 2041:2046 384-well format 2032:2046 384-well format 2032:2046 Using two D2 dopamine receptor cellular models (i.e. CHO-D2L and HEK-AC6/D2L), we have converted our 48-well sensitization assay (>20 steps 4-5 days) to a five-step, single day assay in 384-well format. 24514897 2 85 theme Gαi/o-linked 338:349 arg1 receptors 351:359 Gαi/o-linked receptors 338:359 Gαi/o-linked receptors 338:359 Acute activation of Gαi/o-linked receptors inhibits AC activity, whereas persistent activation of these receptors results in heterologous sensitization of AC and increased levels of intracellular cAMP. 24514897 0 86 theme screening 116:124 arg1 applications 126:137 siRNA screening applications 110:137 siRNA screening applications 110:137 Drug-induced sensitization of adenylyl cyclase: assay streamlining and miniaturization for small molecule and siRNA screening applications. 24514897 6 87 theme Previous 1141:1148 arg1 studies 1150:1156 Previous studies 1141:1156 Previous studies 1141:1156 Previous studies have implicated kinase and Gbγ signaling as overlapping components that regulate the heterologous sensitization of AC. 24514897 8 88 theme wash 1676:1679 arg1 steps 1681:1685 multiple wash steps 1667:1685 multiple wash steps 1667:1685 Previous approaches to study sensitization are generally cumbersome involving continuous cell culture maintenance as well as a complex methodology for measuring cAMP accumulation that involves multiple wash steps. 24514897 0 89 theme adenylyl 30:37 arg1 cyclase 39:45 adenylyl cyclase 30:45 adenylyl cyclase 30:45 Drug-induced sensitization of adenylyl cyclase: assay streamlining and miniaturization for small molecule and siRNA screening applications. 24514897 5 90 theme adaptive 991:998 arg1 response 1000:1007 this adaptive response 986:1007 this adaptive response 986:1007 The lack of mechanistic data presumably reflects the complexity involved with this adaptive response, suggesting that nonbiased approaches could aid in identifying the molecular pathways involved in heterologous sensitization of AC. 24514897 2 91 theme heterologous 443:454 arg1 sensitization 456:468 heterologous sensitization 443:468 heterologous sensitization of AC 443:474 Acute activation of Gαi/o-linked receptors inhibits AC activity, whereas persistent activation of these receptors results in heterologous sensitization of AC and increased levels of intracellular cAMP. 24514897 2 92 theme intracellular 500:512 arg1 cAMP 514:517 intracellular cAMP 500:517 intracellular cAMP 500:517 Acute activation of Gαi/o-linked receptors inhibits AC activity, whereas persistent activation of these receptors results in heterologous sensitization of AC and increased levels of intracellular cAMP. 24514897 11 93 used used 2168:2171 arg2 design 2141:2146 this assay design 2130:2146 this assay design 2130:2146 This new format is amenable to small molecule screening, and we demonstrate that this assay design can also be readily used for reverse transfection of siRNA in anticipation of targeted siRNA library screening. 24514897 3 94 theme several 672:678 arg1 receptors 747:755 μ opioid receptors 738:755 μ opioid receptors 738:755 Previous studies have demonstrated that this enhancement of AC responsiveness is observed both in vitro and in vivo following the chronic activation of several types of Gαi/o-linked receptors including D2 dopamine and μ opioid receptors. 24514897 3 94 theme several 672:678 arg1 types 680:684 several types 672:684 several types of Gαi/o-linked receptors including D2 dopamine and μ opioid receptors 672:755 Previous studies have demonstrated that this enhancement of AC responsiveness is observed both in vitro and in vivo following the chronic activation of several types of Gαi/o-linked receptors including D2 dopamine and μ opioid receptors. 24514897 3 94 theme several 672:678 arg1 dopamine 725:732 D2 dopamine 722:732 D2 dopamine 722:732 Previous studies have demonstrated that this enhancement of AC responsiveness is observed both in vitro and in vivo following the chronic activation of several types of Gαi/o-linked receptors including D2 dopamine and μ opioid receptors. 24514897 5 95 theme molecular 1076:1084 arg1 pathways 1086:1093 the molecular pathways 1072:1093 the molecular pathways involved in heterologous sensitization of AC 1072:1138 The lack of mechanistic data presumably reflects the complexity involved with this adaptive response, suggesting that nonbiased approaches could aid in identifying the molecular pathways involved in heterologous sensitization of AC. 24514897 3 96 theme D2 722:723 arg1 dopamine 725:732 D2 dopamine 722:732 D2 dopamine 722:732 Previous studies have demonstrated that this enhancement of AC responsiveness is observed both in vitro and in vivo following the chronic activation of several types of Gαi/o-linked receptors including D2 dopamine and μ opioid receptors. 24514897 8 97 theme study 1497:1501 arg1 sensitization 1503:1515 study sensitization 1497:1515 study sensitization 1497:1515 Previous approaches to study sensitization are generally cumbersome involving continuous cell culture maintenance as well as a complex methodology for measuring cAMP accumulation that involves multiple wash steps. 24514897 9 98 theme assay 1733:1737 arg1 development 1698:1708 the development 1694:1708 the development of a robust cell-based assay that can be used for high throughput screening (HTS) in a 384 well format 1694:1811 Thus, the development of a robust cell-based assay that can be used for high throughput screening (HTS) in a 384 well format would facilitate future studies. 24514897 6 99 theme Gbγ 1185:1187 arg1 signaling 1189:1197 kinase and Gbγ signaling 1174:1197 kinase and Gbγ signaling 1174:1197 Previous studies have implicated kinase and Gbγ signaling as overlapping components that regulate the heterologous sensitization of AC. 24514897 6 99 theme Gbγ 1185:1187 arg1 components 1214:1223 overlapping components 1202:1223 overlapping components that regulate the heterologous sensitization of AC 1202:1274 Previous studies have implicated kinase and Gbγ signaling as overlapping components that regulate the heterologous sensitization of AC. 24514897 10 100 theme sensitization 1955:1967 arg1 days 1990:1993 >20 steps 4-5 days 1976:1993 >20 steps 4-5 days 1976:1993 Using two D2 dopamine receptor cellular models (i.e. CHO-D2L and HEK-AC6/D2L), we have converted our 48-well sensitization assay (>20 steps 4-5 days) to a five-step, single day assay in 384-well format. 24514897 10 100 theme sensitization 1955:1967 arg1 assay 1969:1973 our 48-well sensitization assay 1943:1973 our 48-well sensitization assay (>20 steps 4-5 days) 1943:1994 Using two D2 dopamine receptor cellular models (i.e. CHO-D2L and HEK-AC6/D2L), we have converted our 48-well sensitization assay (>20 steps 4-5 days) to a five-step, single day assay in 384-well format. 24514897 3 101 theme Previous 520:527 arg1 studies 529:535 Previous studies 520:535 Previous studies 520:535 Previous studies have demonstrated that this enhancement of AC responsiveness is observed both in vitro and in vivo following the chronic activation of several types of Gαi/o-linked receptors including D2 dopamine and μ opioid receptors. 24514897 1 102 theme neuropsychiatric 225:240 arg1 disease 309:315 Parkinson's disease 297:315 Parkinson's disease 297:315 Sensitization of adenylyl cyclase (AC) signaling has been implicated in a variety of neuropsychiatric and neurologic disorders including substance abuse and Parkinson's disease. 24514897 1 102 theme neuropsychiatric 225:240 arg1 disorders 257:265 neuropsychiatric and neurologic disorders 225:265 neuropsychiatric and neurologic disorders including substance abuse and Parkinson's disease 225:315 Sensitization of adenylyl cyclase (AC) signaling has been implicated in a variety of neuropsychiatric and neurologic disorders including substance abuse and Parkinson's disease. 24514897 1 102 theme neuropsychiatric 225:240 arg1 abuse 287:291 substance abuse 277:291 substance abuse 277:291 Sensitization of adenylyl cyclase (AC) signaling has been implicated in a variety of neuropsychiatric and neurologic disorders including substance abuse and Parkinson's disease. 24514897 0 103 dep sensitization 13:25 arg1 assay 48:52 assay 48:52 assay 48:52 Drug-induced sensitization of adenylyl cyclase: assay streamlining and miniaturization for small molecule and siRNA screening applications. 24514897 0 103 dep sensitization 13:25 arg1 miniaturization 71:85 miniaturization 71:85 miniaturization 71:85 Drug-induced sensitization of adenylyl cyclase: assay streamlining and miniaturization for small molecule and siRNA screening applications. 24514897 6 104 theme kinase 1174:1179 arg1 signaling 1189:1197 kinase and Gbγ signaling 1174:1197 kinase and Gbγ signaling 1174:1197 Previous studies have implicated kinase and Gbγ signaling as overlapping components that regulate the heterologous sensitization of AC. 24514897 6 104 theme kinase 1174:1179 arg1 components 1214:1223 overlapping components 1202:1223 overlapping components that regulate the heterologous sensitization of AC 1202:1274 Previous studies have implicated kinase and Gbγ signaling as overlapping components that regulate the heterologous sensitization of AC. 24514897 3 105 theme opioid 740:745 arg1 receptors 747:755 μ opioid receptors 738:755 μ opioid receptors 738:755 Previous studies have demonstrated that this enhancement of AC responsiveness is observed both in vitro and in vivo following the chronic activation of several types of Gαi/o-linked receptors including D2 dopamine and μ opioid receptors. 24514897 4 106 theme mechanism 841:849 arg1 s 851:851 the mechanism(s) 837:852 the mechanism(s) that underlie this phenomenon 837:882 Although heterologous sensitization of AC was first reported four decades ago, the mechanism(s) that underlie this phenomenon remain largely unknown. 24514897 11 107 theme siRNA 2201:2205 arg1 transfection 2185:2196 reverse transfection 2177:2196 reverse transfection of siRNA in anticipation of targeted siRNA library screening 2177:2257 This new format is amenable to small molecule screening, and we demonstrate that this assay design can also be readily used for reverse transfection of siRNA in anticipation of targeted siRNA library screening. 24514897 1 108 theme neurologic 246:255 arg1 disease 309:315 Parkinson's disease 297:315 Parkinson's disease 297:315 Sensitization of adenylyl cyclase (AC) signaling has been implicated in a variety of neuropsychiatric and neurologic disorders including substance abuse and Parkinson's disease. 24514897 1 108 theme neurologic 246:255 arg1 disorders 257:265 neuropsychiatric and neurologic disorders 225:265 neuropsychiatric and neurologic disorders including substance abuse and Parkinson's disease 225:315 Sensitization of adenylyl cyclase (AC) signaling has been implicated in a variety of neuropsychiatric and neurologic disorders including substance abuse and Parkinson's disease. 24514897 1 108 theme neurologic 246:255 arg1 abuse 287:291 substance abuse 277:291 substance abuse 277:291 Sensitization of adenylyl cyclase (AC) signaling has been implicated in a variety of neuropsychiatric and neurologic disorders including substance abuse and Parkinson's disease. 28615211 12 0 theme pseudovirion 2237:2248 arg1 vaccines 2250:2257 VSVΔG pseudovirion vaccines 2231:2257 VSVΔG pseudovirion vaccines 2231:2257 VSVΔG pseudovirion vaccines may prove as efficacious and have better safety, but they have not been tested to date. 28615211 13 1 theme Ebola 2407:2411 arg1 glycoprotein 2419:2430 Ebola virus glycoprotein 2407:2430 Ebola virus glycoprotein 2407:2430 Thus, we tested the efficacy of VSVΔG pseudovirions bearing Ebola virus glycoprotein as a vaccine platform. 28615211 13 1 theme Ebola 2407:2411 arg1 platform 2445:2452 a vaccine platform 2435:2452 a vaccine platform 2435:2452 Thus, we tested the efficacy of VSVΔG pseudovirions bearing Ebola virus glycoprotein as a vaccine platform. 28615211 7 2 theme N-linked 1101:1108 arg1 glycans 1110:1116 GP1 N-linked glycans 1097:1116 GP1 N-linked glycans 1097:1116 As N-linked glycans are thought to shield conserved regions of the EBOV GP receptor-binding domain (RBD), thereby blocking epitopes within the RBD, we also tested whether VSVΔG bearing EBOV GPs that lack GP1 N-linked glycans provided effective immunity against challenge with ma-EBOV or a more distantly related virus, Sudan virus. 28615211 6 3 theme prime/boost 812:822 arg1 regimen 824:830 The prime/boost regimen 808:830 The prime/boost regimen 808:830 The prime/boost regimen provided significantly better protection than a single dose. 28615211 9 4 theme GP-specific 1610:1620 arg1 Ig 1622:1623 EBOV GP-specific Ig 1605:1623 EBOV GP-specific Ig 1605:1623 As reported for other EBOV vaccine platforms, the protection conferred correlated with the quantity of EBOV GP-specific Ig produced but not with the production of neutralizing antibodies. 28615211 3 5 theme EBOV 564:567 arg1 GP 583:584 GP 583:584 GP 583:584 To expand the vaccine options potentially available, we assessed protection conferred by an EBOV vaccine composed of vesicular stomatitis virus pseudovirions that lack native G glycoprotein (VSVΔG) and bear EBOV glycoprotein (GP). 28615211 3 5 theme EBOV 564:567 arg1 glycoprotein 569:580 bear EBOV glycoprotein 559:580 bear EBOV glycoprotein (GP) 559:585 To expand the vaccine options potentially available, we assessed protection conferred by an EBOV vaccine composed of vesicular stomatitis virus pseudovirions that lack native G glycoprotein (VSVΔG) and bear EBOV glycoprotein (GP). 28615211 9 6 theme other 1518:1522 arg1 platforms 1537:1545 other EBOV vaccine platforms 1518:1545 other EBOV vaccine platforms 1518:1545 As reported for other EBOV vaccine platforms, the protection conferred correlated with the quantity of EBOV GP-specific Ig produced but not with the production of neutralizing antibodies. 28615211 10 7 theme EBOV 1712:1715 arg1 platform 1774:1781 a successful vaccination platform 1749:1781 a successful vaccination platform 1749:1781 Our results show that EBOV GP/VSVΔG pseudovirions serve as a successful vaccination platform in a rodent model of Ebola virus disease and that GP1 N-glycan loss does not influence immunogenicity or vaccination success.IMPORTANCE The West African Ebola virus epidemic was the largest to date, with more than 28,000 people infected. 28615211 10 7 theme EBOV 1712:1715 arg1 immunogenicity 1870:1883 immunogenicity 1870:1883 immunogenicity 1870:1883 Our results show that EBOV GP/VSVΔG pseudovirions serve as a successful vaccination platform in a rodent model of Ebola virus disease and that GP1 N-glycan loss does not influence immunogenicity or vaccination success.IMPORTANCE The West African Ebola virus epidemic was the largest to date, with more than 28,000 people infected. 28615211 10 7 theme EBOV 1712:1715 arg1 success.IMPORTANCE 1900:1917 vaccination success.IMPORTANCE 1888:1917 vaccination success.IMPORTANCE 1888:1917 Our results show that EBOV GP/VSVΔG pseudovirions serve as a successful vaccination platform in a rodent model of Ebola virus disease and that GP1 N-glycan loss does not influence immunogenicity or vaccination success.IMPORTANCE The West African Ebola virus epidemic was the largest to date, with more than 28,000 people infected. 28615211 10 7 theme EBOV 1712:1715 arg1 pseudovirions 1726:1738 EBOV GP/VSVΔG pseudovirions 1712:1738 EBOV GP/VSVΔG pseudovirions 1712:1738 Our results show that EBOV GP/VSVΔG pseudovirions serve as a successful vaccination platform in a rodent model of Ebola virus disease and that GP1 N-glycan loss does not influence immunogenicity or vaccination success.IMPORTANCE The West African Ebola virus epidemic was the largest to date, with more than 28,000 people infected. 28615211 1 8 theme public 253:258 arg1 burden 267:272 a significant public health burden 239:272 a significant public health burden caused by filoviral infections 239:303 The recent Ebola virus (EBOV) epidemic in West Africa demonstrates the potential for a significant public health burden caused by filoviral infections. 28615211 4 9 theme infection 634:642 arg1 round 625:629 a single round 616:629 a single round of infection 616:642 These pseudovirions mediate a single round of infection. 28615211 10 10 theme vaccination 1888:1898 arg1 platform 1774:1781 a successful vaccination platform 1749:1781 a successful vaccination platform 1749:1781 Our results show that EBOV GP/VSVΔG pseudovirions serve as a successful vaccination platform in a rodent model of Ebola virus disease and that GP1 N-glycan loss does not influence immunogenicity or vaccination success.IMPORTANCE The West African Ebola virus epidemic was the largest to date, with more than 28,000 people infected. 28615211 10 10 theme vaccination 1888:1898 arg1 immunogenicity 1870:1883 immunogenicity 1870:1883 immunogenicity 1870:1883 Our results show that EBOV GP/VSVΔG pseudovirions serve as a successful vaccination platform in a rodent model of Ebola virus disease and that GP1 N-glycan loss does not influence immunogenicity or vaccination success.IMPORTANCE The West African Ebola virus epidemic was the largest to date, with more than 28,000 people infected. 28615211 10 10 theme vaccination 1888:1898 arg1 success.IMPORTANCE 1900:1917 vaccination success.IMPORTANCE 1888:1917 vaccination success.IMPORTANCE 1888:1917 Our results show that EBOV GP/VSVΔG pseudovirions serve as a successful vaccination platform in a rodent model of Ebola virus disease and that GP1 N-glycan loss does not influence immunogenicity or vaccination success.IMPORTANCE The West African Ebola virus epidemic was the largest to date, with more than 28,000 people infected. 28615211 10 10 theme vaccination 1888:1898 arg1 pseudovirions 1726:1738 EBOV GP/VSVΔG pseudovirions 1712:1738 EBOV GP/VSVΔG pseudovirions 1712:1738 Our results show that EBOV GP/VSVΔG pseudovirions serve as a successful vaccination platform in a rodent model of Ebola virus disease and that GP1 N-glycan loss does not influence immunogenicity or vaccination success.IMPORTANCE The West African Ebola virus epidemic was the largest to date, with more than 28,000 people infected. 28615211 14 11 gly glycoprotein 2491:2502 arg1 glycoprotein 2491:2502 wild-type Ebola virus glycoprotein 2469:2502 wild-type Ebola virus glycoprotein 2469:2502 We found that wild-type Ebola virus glycoprotein, in the context of this platform, provides robust protection of EBOV-challenged mice. 28615211 3 12 theme G 532:532 arg1 glycoprotein 534:545 native G glycoprotein 525:545 native G glycoprotein (VSVΔG) 525:553 To expand the vaccine options potentially available, we assessed protection conferred by an EBOV vaccine composed of vesicular stomatitis virus pseudovirions that lack native G glycoprotein (VSVΔG) and bear EBOV glycoprotein (GP). 28615211 3 12 theme G 532:532 arg1 VSVΔG 548:552 VSVΔG 548:552 VSVΔG 548:552 To expand the vaccine options potentially available, we assessed protection conferred by an EBOV vaccine composed of vesicular stomatitis virus pseudovirions that lack native G glycoprotein (VSVΔG) and bear EBOV glycoprotein (GP). 28615211 11 13 theme trial 2074:2078 arg1 strategy 2092:2099 a trial vaccination strategy 2072:2099 a trial vaccination strategy in West Africa 2072:2114 No FDA-approved vaccines are yet available, but in a trial vaccination strategy in West Africa, recombinant, infectious VSV encoding the Ebola virus glycoprotein effectively prevented virus-associated disease. 28615211 3 14 theme bear 559:562 arg1 GP 583:584 GP 583:584 GP 583:584 To expand the vaccine options potentially available, we assessed protection conferred by an EBOV vaccine composed of vesicular stomatitis virus pseudovirions that lack native G glycoprotein (VSVΔG) and bear EBOV glycoprotein (GP). 28615211 3 14 theme bear 559:562 arg1 glycoprotein 569:580 bear EBOV glycoprotein 559:580 bear EBOV glycoprotein (GP) 559:585 To expand the vaccine options potentially available, we assessed protection conferred by an EBOV vaccine composed of vesicular stomatitis virus pseudovirions that lack native G glycoprotein (VSVΔG) and bear EBOV glycoprotein (GP). 28615211 10 15 theme African 1928:1934 arg1 virus 1942:1946 The West African Ebola virus epidemic 1919:1955 The West African Ebola virus epidemic 1919:1955 Our results show that EBOV GP/VSVΔG pseudovirions serve as a successful vaccination platform in a rodent model of Ebola virus disease and that GP1 N-glycan loss does not influence immunogenicity or vaccination success.IMPORTANCE The West African Ebola virus epidemic was the largest to date, with more than 28,000 people infected. 28615211 10 15 theme African 1928:1934 arg1 largest 1965:1971 largest 1965:1971 largest 1965:1971 Our results show that EBOV GP/VSVΔG pseudovirions serve as a successful vaccination platform in a rodent model of Ebola virus disease and that GP1 N-glycan loss does not influence immunogenicity or vaccination success.IMPORTANCE The West African Ebola virus epidemic was the largest to date, with more than 28,000 people infected. 28615211 0 16 theme Ebola 123:127 arg1 Challenge 135:143 Ebola Virus Challenge 123:143 Ebola Virus Challenge in Mice 123:151 Vesicular Stomatitis Virus Pseudotyped with Ebola Virus Glycoprotein Serves as a Protective, Noninfectious Vaccine against Ebola Virus Challenge in Mice. 28615211 1 17 theme epidemic 184:191 arg1 EBOV 178:181 EBOV 178:181 EBOV 178:181 The recent Ebola virus (EBOV) epidemic in West Africa demonstrates the potential for a significant public health burden caused by filoviral infections. 28615211 1 17 theme epidemic 184:191 arg1 virus 171:175 The recent Ebola virus 154:175 The recent Ebola virus (EBOV) epidemic in West Africa 154:206 The recent Ebola virus (EBOV) epidemic in West Africa demonstrates the potential for a significant public health burden caused by filoviral infections. 28615211 8 18 link N-linked 1308:1315 arg1 glycans 1317:1323 N-linked glycans 1308:1323 N-linked glycans 1308:1323 Using a prime/boost strategy, high doses of GP/VSVΔG partially or fully denuded of N-linked glycans on GP1 protected mice against ma-EBOV challenge, but these mutants were no more effective than wild-type (WT) GP/VSVΔG and did not provide cross protection against Sudan virus. 28615211 13 19 gly glycoprotein 2419:2430 arg1 glycoprotein 2419:2430 Ebola virus glycoprotein 2407:2430 Ebola virus glycoprotein 2407:2430 Thus, we tested the efficacy of VSVΔG pseudovirions bearing Ebola virus glycoprotein as a vaccine platform. 28615211 13 19 gly glycoprotein 2419:2430 arg1 platform 2445:2452 a vaccine platform 2435:2452 a vaccine platform 2435:2452 Thus, we tested the efficacy of VSVΔG pseudovirions bearing Ebola virus glycoprotein as a vaccine platform. 28615211 8 20 theme high 1255:1258 arg1 doses 1260:1264 high doses 1255:1264 high doses of GP/VSVΔG partially or fully denuded of N-linked glycans on GP1 1255:1330 Using a prime/boost strategy, high doses of GP/VSVΔG partially or fully denuded of N-linked glycans on GP1 protected mice against ma-EBOV challenge, but these mutants were no more effective than wild-type (WT) GP/VSVΔG and did not provide cross protection against Sudan virus. 28615211 9 21 theme antibodies 1678:1687 arg1 production 1651:1660 the production 1647:1660 the production of neutralizing antibodies 1647:1687 As reported for other EBOV vaccine platforms, the protection conferred correlated with the quantity of EBOV GP-specific Ig produced but not with the production of neutralizing antibodies. 28615211 8 22 theme wild-type 1420:1428 arg1 GP/VSVΔG 1435:1442 wild-type (WT) GP/VSVΔG 1420:1442 wild-type (WT) GP/VSVΔG 1420:1442 Using a prime/boost strategy, high doses of GP/VSVΔG partially or fully denuded of N-linked glycans on GP1 protected mice against ma-EBOV challenge, but these mutants were no more effective than wild-type (WT) GP/VSVΔG and did not provide cross protection against Sudan virus. 28615211 1 23 from Africa 201:206 arg1 epidemic 184:191 epidemic 184:191 epidemic 184:191 The recent Ebola virus (EBOV) epidemic in West Africa demonstrates the potential for a significant public health burden caused by filoviral infections. 28615211 13 24 theme virus 2413:2417 arg1 glycoprotein 2419:2430 Ebola virus glycoprotein 2407:2430 Ebola virus glycoprotein 2407:2430 Thus, we tested the efficacy of VSVΔG pseudovirions bearing Ebola virus glycoprotein as a vaccine platform. 28615211 13 24 theme virus 2413:2417 arg1 platform 2445:2452 a vaccine platform 2435:2452 a vaccine platform 2435:2452 Thus, we tested the efficacy of VSVΔG pseudovirions bearing Ebola virus glycoprotein as a vaccine platform. 28615211 10 25 theme successful 1751:1760 arg1 platform 1774:1781 a successful vaccination platform 1749:1781 a successful vaccination platform 1749:1781 Our results show that EBOV GP/VSVΔG pseudovirions serve as a successful vaccination platform in a rodent model of Ebola virus disease and that GP1 N-glycan loss does not influence immunogenicity or vaccination success.IMPORTANCE The West African Ebola virus epidemic was the largest to date, with more than 28,000 people infected. 28615211 10 25 theme successful 1751:1760 arg1 immunogenicity 1870:1883 immunogenicity 1870:1883 immunogenicity 1870:1883 Our results show that EBOV GP/VSVΔG pseudovirions serve as a successful vaccination platform in a rodent model of Ebola virus disease and that GP1 N-glycan loss does not influence immunogenicity or vaccination success.IMPORTANCE The West African Ebola virus epidemic was the largest to date, with more than 28,000 people infected. 28615211 10 25 theme successful 1751:1760 arg1 success.IMPORTANCE 1900:1917 vaccination success.IMPORTANCE 1888:1917 vaccination success.IMPORTANCE 1888:1917 Our results show that EBOV GP/VSVΔG pseudovirions serve as a successful vaccination platform in a rodent model of Ebola virus disease and that GP1 N-glycan loss does not influence immunogenicity or vaccination success.IMPORTANCE The West African Ebola virus epidemic was the largest to date, with more than 28,000 people infected. 28615211 10 25 theme successful 1751:1760 arg1 pseudovirions 1726:1738 EBOV GP/VSVΔG pseudovirions 1712:1738 EBOV GP/VSVΔG pseudovirions 1712:1738 Our results show that EBOV GP/VSVΔG pseudovirions serve as a successful vaccination platform in a rodent model of Ebola virus disease and that GP1 N-glycan loss does not influence immunogenicity or vaccination success.IMPORTANCE The West African Ebola virus epidemic was the largest to date, with more than 28,000 people infected. 28615211 14 26 theme robust 2547:2552 arg1 protection 2554:2563 robust protection 2547:2563 robust protection of EBOV-challenged mice 2547:2587 We found that wild-type Ebola virus glycoprotein, in the context of this platform, provides robust protection of EBOV-challenged mice. 28615211 15 27 theme glycan 2634:2639 arg1 regions 2670:2676 the heavy glycan shield surrounding conserved regions 2624:2676 the heavy glycan shield surrounding conserved regions of the glycoprotein 2624:2696 Further, we found that removal of the heavy glycan shield surrounding conserved regions of the glycoprotein does not enhance vaccine efficacy. 28615211 5 28 theme vaccination 678:688 arg1 regimens 690:697 Both single-dose and prime/boost vaccination regimens 645:697 Both single-dose and prime/boost vaccination regimens 645:697 Both single-dose and prime/boost vaccination regimens protected mice against lethal challenge with mouse-adapted Ebola virus (ma-EBOV) in a dose-dependent manner. 28615211 14 29 theme wild-type 2469:2477 arg1 glycoprotein 2491:2502 wild-type Ebola virus glycoprotein 2469:2502 wild-type Ebola virus glycoprotein 2469:2502 We found that wild-type Ebola virus glycoprotein, in the context of this platform, provides robust protection of EBOV-challenged mice. 28615211 11 30 theme virus 2164:2168 arg1 glycoprotein 2170:2181 the Ebola virus glycoprotein 2154:2181 the Ebola virus glycoprotein 2154:2181 No FDA-approved vaccines are yet available, but in a trial vaccination strategy in West Africa, recombinant, infectious VSV encoding the Ebola virus glycoprotein effectively prevented virus-associated disease. 28615211 12 31 theme better 2293:2298 arg1 safety 2300:2305 better safety 2293:2305 better safety 2293:2305 VSVΔG pseudovirion vaccines may prove as efficacious and have better safety, but they have not been tested to date. 28615211 7 32 theme Sudan 1212:1216 arg1 virus 1205:1209 a more distantly related virus 1180:1209 a more distantly related virus 1180:1209 As N-linked glycans are thought to shield conserved regions of the EBOV GP receptor-binding domain (RBD), thereby blocking epitopes within the RBD, we also tested whether VSVΔG bearing EBOV GPs that lack GP1 N-linked glycans provided effective immunity against challenge with ma-EBOV or a more distantly related virus, Sudan virus. 28615211 7 32 theme Sudan 1212:1216 arg1 virus 1218:1222 Sudan virus 1212:1222 Sudan virus 1212:1222 As N-linked glycans are thought to shield conserved regions of the EBOV GP receptor-binding domain (RBD), thereby blocking epitopes within the RBD, we also tested whether VSVΔG bearing EBOV GPs that lack GP1 N-linked glycans provided effective immunity against challenge with ma-EBOV or a more distantly related virus, Sudan virus. 28615211 7 33 theme domain 985:990 arg1 regions 945:951 conserved regions 935:951 conserved regions of the EBOV GP receptor-binding domain (RBD) 935:996 As N-linked glycans are thought to shield conserved regions of the EBOV GP receptor-binding domain (RBD), thereby blocking epitopes within the RBD, we also tested whether VSVΔG bearing EBOV GPs that lack GP1 N-linked glycans provided effective immunity against challenge with ma-EBOV or a more distantly related virus, Sudan virus. 28615211 7 34 theme GP 965:966 arg1 RBD 993:995 RBD 993:995 RBD 993:995 As N-linked glycans are thought to shield conserved regions of the EBOV GP receptor-binding domain (RBD), thereby blocking epitopes within the RBD, we also tested whether VSVΔG bearing EBOV GPs that lack GP1 N-linked glycans provided effective immunity against challenge with ma-EBOV or a more distantly related virus, Sudan virus. 28615211 7 34 theme GP 965:966 arg1 domain 985:990 the EBOV GP receptor-binding domain 956:990 the EBOV GP receptor-binding domain (RBD) 956:996 As N-linked glycans are thought to shield conserved regions of the EBOV GP receptor-binding domain (RBD), thereby blocking epitopes within the RBD, we also tested whether VSVΔG bearing EBOV GPs that lack GP1 N-linked glycans provided effective immunity against challenge with ma-EBOV or a more distantly related virus, Sudan virus. 28615211 1 35 theme recent 158:163 arg1 EBOV 178:181 EBOV 178:181 EBOV 178:181 The recent Ebola virus (EBOV) epidemic in West Africa demonstrates the potential for a significant public health burden caused by filoviral infections. 28615211 1 35 theme recent 158:163 arg1 virus 171:175 The recent Ebola virus 154:175 The recent Ebola virus (EBOV) epidemic in West Africa 154:206 The recent Ebola virus (EBOV) epidemic in West Africa demonstrates the potential for a significant public health burden caused by filoviral infections. 28615211 11 36 theme virus-associated 2205:2220 arg1 disease 2222:2228 virus-associated disease 2205:2228 virus-associated disease 2205:2228 No FDA-approved vaccines are yet available, but in a trial vaccination strategy in West Africa, recombinant, infectious VSV encoding the Ebola virus glycoprotein effectively prevented virus-associated disease. 28615211 15 37 theme vaccine 2715:2721 arg1 efficacy 2723:2730 vaccine efficacy 2715:2730 vaccine efficacy 2715:2730 Further, we found that removal of the heavy glycan shield surrounding conserved regions of the glycoprotein does not enhance vaccine efficacy. 28615211 13 38 theme VSVΔG 2379:2383 arg1 pseudovirions 2385:2397 VSVΔG pseudovirions 2379:2397 VSVΔG pseudovirions bearing Ebola virus glycoprotein as a vaccine platform 2379:2452 Thus, we tested the efficacy of VSVΔG pseudovirions bearing Ebola virus glycoprotein as a vaccine platform. 28615211 5 39 theme mouse-adapted 744:756 arg1 virus 764:768 mouse-adapted Ebola virus 744:768 mouse-adapted Ebola virus (ma-EBOV) 744:778 Both single-dose and prime/boost vaccination regimens protected mice against lethal challenge with mouse-adapted Ebola virus (ma-EBOV) in a dose-dependent manner. 28615211 5 39 theme mouse-adapted 744:756 arg1 ma-EBOV 771:777 ma-EBOV 771:777 ma-EBOV 771:777 Both single-dose and prime/boost vaccination regimens protected mice against lethal challenge with mouse-adapted Ebola virus (ma-EBOV) in a dose-dependent manner. 28615211 0 40 theme Ebola 44:48 arg1 Glycoprotein 56:67 Ebola Virus Glycoprotein 44:67 Ebola Virus Glycoprotein 44:67 Vesicular Stomatitis Virus Pseudotyped with Ebola Virus Glycoprotein Serves as a Protective, Noninfectious Vaccine against Ebola Virus Challenge in Mice. 28615211 8 41 theme Sudan 1489:1493 arg1 virus 1495:1499 Sudan virus 1489:1499 Sudan virus 1489:1499 Using a prime/boost strategy, high doses of GP/VSVΔG partially or fully denuded of N-linked glycans on GP1 protected mice against ma-EBOV challenge, but these mutants were no more effective than wild-type (WT) GP/VSVΔG and did not provide cross protection against Sudan virus. 28615211 11 42 theme recombinant 2117:2127 arg1 VSV 2141:2143 recombinant, infectious VSV 2117:2143 recombinant, infectious VSV encoding the Ebola virus glycoprotein 2117:2181 No FDA-approved vaccines are yet available, but in a trial vaccination strategy in West Africa, recombinant, infectious VSV encoding the Ebola virus glycoprotein effectively prevented virus-associated disease. 28615211 0 43 theme Vesicular 0:8 arg1 Virus 21:25 Vesicular Stomatitis Virus 0:25 Vesicular Stomatitis Virus Pseudotyped with Ebola Virus Glycoprotein 0:67 Vesicular Stomatitis Virus Pseudotyped with Ebola Virus Glycoprotein Serves as a Protective, Noninfectious Vaccine against Ebola Virus Challenge in Mice. 28615211 0 43 theme Vesicular 0:8 arg1 Vaccine 107:113 a Protective, Noninfectious Vaccine 79:113 a Protective, Noninfectious Vaccine against Ebola Virus Challenge in Mice 79:151 Vesicular Stomatitis Virus Pseudotyped with Ebola Virus Glycoprotein Serves as a Protective, Noninfectious Vaccine against Ebola Virus Challenge in Mice. 28615211 1 44 theme health 260:265 arg1 burden 267:272 a significant public health burden 239:272 a significant public health burden caused by filoviral infections 239:303 The recent Ebola virus (EBOV) epidemic in West Africa demonstrates the potential for a significant public health burden caused by filoviral infections. 28615211 9 45 theme EBOV 1524:1527 arg1 platforms 1537:1545 other EBOV vaccine platforms 1518:1545 other EBOV vaccine platforms 1518:1545 As reported for other EBOV vaccine platforms, the protection conferred correlated with the quantity of EBOV GP-specific Ig produced but not with the production of neutralizing antibodies. 28615211 8 46 theme ma-EBOV 1355:1361 arg1 challenge 1363:1371 ma-EBOV challenge 1355:1371 ma-EBOV challenge 1355:1371 Using a prime/boost strategy, high doses of GP/VSVΔG partially or fully denuded of N-linked glycans on GP1 protected mice against ma-EBOV challenge, but these mutants were no more effective than wild-type (WT) GP/VSVΔG and did not provide cross protection against Sudan virus. 28615211 3 47 theme EBOV 449:452 arg1 vaccine 454:460 an EBOV vaccine 446:460 an EBOV vaccine composed of vesicular stomatitis virus pseudovirions that lack native G glycoprotein (VSVΔG) and bear EBOV glycoprotein (GP) 446:585 To expand the vaccine options potentially available, we assessed protection conferred by an EBOV vaccine composed of vesicular stomatitis virus pseudovirions that lack native G glycoprotein (VSVΔG) and bear EBOV glycoprotein (GP). 28615211 6 48 theme single 880:885 arg1 dose 887:890 a single dose 878:890 a single dose 878:890 The prime/boost regimen provided significantly better protection than a single dose. 28615211 3 49 theme available 399:407 arg1 options 379:385 the vaccine options 367:385 the vaccine options potentially available 367:407 To expand the vaccine options potentially available, we assessed protection conferred by an EBOV vaccine composed of vesicular stomatitis virus pseudovirions that lack native G glycoprotein (VSVΔG) and bear EBOV glycoprotein (GP). 28615211 10 50 theme disease 1816:1822 arg1 model 1795:1799 a rodent model 1786:1799 a rodent model of Ebola virus disease 1786:1822 Our results show that EBOV GP/VSVΔG pseudovirions serve as a successful vaccination platform in a rodent model of Ebola virus disease and that GP1 N-glycan loss does not influence immunogenicity or vaccination success.IMPORTANCE The West African Ebola virus epidemic was the largest to date, with more than 28,000 people infected. 28615211 15 51 theme regions 2670:2676 arg1 removal 2613:2619 removal 2613:2619 removal of the heavy glycan shield surrounding conserved regions of the glycoprotein 2613:2696 Further, we found that removal of the heavy glycan shield surrounding conserved regions of the glycoprotein does not enhance vaccine efficacy. 28615211 1 52 theme filoviral 284:292 arg1 infections 294:303 filoviral infections 284:303 filoviral infections 284:303 The recent Ebola virus (EBOV) epidemic in West Africa demonstrates the potential for a significant public health burden caused by filoviral infections. 28615211 14 53 theme virus 2485:2489 arg1 glycoprotein 2491:2502 wild-type Ebola virus glycoprotein 2469:2502 wild-type Ebola virus glycoprotein 2469:2502 We found that wild-type Ebola virus glycoprotein, in the context of this platform, provides robust protection of EBOV-challenged mice. 28615211 15 54 theme surrounding 2648:2658 arg1 regions 2670:2676 the heavy glycan shield surrounding conserved regions 2624:2676 the heavy glycan shield surrounding conserved regions of the glycoprotein 2624:2696 Further, we found that removal of the heavy glycan shield surrounding conserved regions of the glycoprotein does not enhance vaccine efficacy. 28615211 10 55 theme Ebola 1804:1808 arg1 disease 1816:1822 Ebola virus disease 1804:1822 Ebola virus disease 1804:1822 Our results show that EBOV GP/VSVΔG pseudovirions serve as a successful vaccination platform in a rodent model of Ebola virus disease and that GP1 N-glycan loss does not influence immunogenicity or vaccination success.IMPORTANCE The West African Ebola virus epidemic was the largest to date, with more than 28,000 people infected. 28615211 3 56 theme vesicular 474:482 arg1 virus 495:499 vesicular stomatitis virus 474:499 vesicular stomatitis virus pseudovirions that lack native G glycoprotein (VSVΔG) and bear EBOV glycoprotein (GP) 474:585 To expand the vaccine options potentially available, we assessed protection conferred by an EBOV vaccine composed of vesicular stomatitis virus pseudovirions that lack native G glycoprotein (VSVΔG) and bear EBOV glycoprotein (GP). 28615211 5 57 theme dose-dependent 785:798 arg1 manner 800:805 a dose-dependent manner 783:805 a dose-dependent manner 783:805 Both single-dose and prime/boost vaccination regimens protected mice against lethal challenge with mouse-adapted Ebola virus (ma-EBOV) in a dose-dependent manner. 28615211 6 58 theme better 855:860 arg1 protection 862:871 significantly better protection 841:871 significantly better protection 841:871 The prime/boost regimen provided significantly better protection than a single dose. 28615211 10 59 theme N-glycan 1837:1844 arg1 loss 1846:1849 GP1 N-glycan loss 1833:1849 GP1 N-glycan loss 1833:1849 Our results show that EBOV GP/VSVΔG pseudovirions serve as a successful vaccination platform in a rodent model of Ebola virus disease and that GP1 N-glycan loss does not influence immunogenicity or vaccination success.IMPORTANCE The West African Ebola virus epidemic was the largest to date, with more than 28,000 people infected. 28615211 0 60 from Challenge 135:143 arg1 Mice 148:151 Mice 148:151 Mice 148:151 Vesicular Stomatitis Virus Pseudotyped with Ebola Virus Glycoprotein Serves as a Protective, Noninfectious Vaccine against Ebola Virus Challenge in Mice. 28615211 7 61 theme related 1197:1203 arg1 virus 1205:1209 a more distantly related virus 1180:1209 a more distantly related virus 1180:1209 As N-linked glycans are thought to shield conserved regions of the EBOV GP receptor-binding domain (RBD), thereby blocking epitopes within the RBD, we also tested whether VSVΔG bearing EBOV GPs that lack GP1 N-linked glycans provided effective immunity against challenge with ma-EBOV or a more distantly related virus, Sudan virus. 28615211 7 61 theme related 1197:1203 arg1 virus 1218:1222 Sudan virus 1212:1222 Sudan virus 1212:1222 As N-linked glycans are thought to shield conserved regions of the EBOV GP receptor-binding domain (RBD), thereby blocking epitopes within the RBD, we also tested whether VSVΔG bearing EBOV GPs that lack GP1 N-linked glycans provided effective immunity against challenge with ma-EBOV or a more distantly related virus, Sudan virus. 28615211 7 62 theme GP1 1097:1099 arg1 glycans 1110:1116 GP1 N-linked glycans 1097:1116 GP1 N-linked glycans 1097:1116 As N-linked glycans are thought to shield conserved regions of the EBOV GP receptor-binding domain (RBD), thereby blocking epitopes within the RBD, we also tested whether VSVΔG bearing EBOV GPs that lack GP1 N-linked glycans provided effective immunity against challenge with ma-EBOV or a more distantly related virus, Sudan virus. 28615211 3 63 theme virus 495:499 arg1 pseudovirions 501:513 vesicular stomatitis virus pseudovirions 474:513 vesicular stomatitis virus pseudovirions that lack native G glycoprotein (VSVΔG) and bear EBOV glycoprotein (GP) 474:585 To expand the vaccine options potentially available, we assessed protection conferred by an EBOV vaccine composed of vesicular stomatitis virus pseudovirions that lack native G glycoprotein (VSVΔG) and bear EBOV glycoprotein (GP). 28615211 7 64 theme N-linked 896:903 arg1 glycans 905:911 N-linked glycans 896:911 N-linked glycans 896:911 As N-linked glycans are thought to shield conserved regions of the EBOV GP receptor-binding domain (RBD), thereby blocking epitopes within the RBD, we also tested whether VSVΔG bearing EBOV GPs that lack GP1 N-linked glycans provided effective immunity against challenge with ma-EBOV or a more distantly related virus, Sudan virus. 28615211 15 65 theme conserved 2660:2668 arg1 regions 2670:2676 the heavy glycan shield surrounding conserved regions 2624:2676 the heavy glycan shield surrounding conserved regions of the glycoprotein 2624:2696 Further, we found that removal of the heavy glycan shield surrounding conserved regions of the glycoprotein does not enhance vaccine efficacy. 28615211 9 66 theme EBOV 1605:1608 arg1 Ig 1622:1623 EBOV GP-specific Ig 1605:1623 EBOV GP-specific Ig 1605:1623 As reported for other EBOV vaccine platforms, the protection conferred correlated with the quantity of EBOV GP-specific Ig produced but not with the production of neutralizing antibodies. 28615211 7 67 link N-linked 896:903 arg1 glycans 905:911 N-linked glycans 896:911 N-linked glycans 896:911 As N-linked glycans are thought to shield conserved regions of the EBOV GP receptor-binding domain (RBD), thereby blocking epitopes within the RBD, we also tested whether VSVΔG bearing EBOV GPs that lack GP1 N-linked glycans provided effective immunity against challenge with ma-EBOV or a more distantly related virus, Sudan virus. 28615211 10 68 theme GP/VSVΔG 1717:1724 arg1 platform 1774:1781 a successful vaccination platform 1749:1781 a successful vaccination platform 1749:1781 Our results show that EBOV GP/VSVΔG pseudovirions serve as a successful vaccination platform in a rodent model of Ebola virus disease and that GP1 N-glycan loss does not influence immunogenicity or vaccination success.IMPORTANCE The West African Ebola virus epidemic was the largest to date, with more than 28,000 people infected. 28615211 10 68 theme GP/VSVΔG 1717:1724 arg1 immunogenicity 1870:1883 immunogenicity 1870:1883 immunogenicity 1870:1883 Our results show that EBOV GP/VSVΔG pseudovirions serve as a successful vaccination platform in a rodent model of Ebola virus disease and that GP1 N-glycan loss does not influence immunogenicity or vaccination success.IMPORTANCE The West African Ebola virus epidemic was the largest to date, with more than 28,000 people infected. 28615211 10 68 theme GP/VSVΔG 1717:1724 arg1 success.IMPORTANCE 1900:1917 vaccination success.IMPORTANCE 1888:1917 vaccination success.IMPORTANCE 1888:1917 Our results show that EBOV GP/VSVΔG pseudovirions serve as a successful vaccination platform in a rodent model of Ebola virus disease and that GP1 N-glycan loss does not influence immunogenicity or vaccination success.IMPORTANCE The West African Ebola virus epidemic was the largest to date, with more than 28,000 people infected. 28615211 10 68 theme GP/VSVΔG 1717:1724 arg1 pseudovirions 1726:1738 EBOV GP/VSVΔG pseudovirions 1712:1738 EBOV GP/VSVΔG pseudovirions 1712:1738 Our results show that EBOV GP/VSVΔG pseudovirions serve as a successful vaccination platform in a rodent model of Ebola virus disease and that GP1 N-glycan loss does not influence immunogenicity or vaccination success.IMPORTANCE The West African Ebola virus epidemic was the largest to date, with more than 28,000 people infected. 28615211 1 69 theme significant 241:251 arg1 burden 267:272 a significant public health burden 239:272 a significant public health burden caused by filoviral infections 239:303 The recent Ebola virus (EBOV) epidemic in West Africa demonstrates the potential for a significant public health burden caused by filoviral infections. 28615211 9 70 theme Ig 1622:1623 arg1 quantity 1593:1600 the quantity 1589:1600 the quantity of EBOV GP-specific Ig produced 1589:1632 As reported for other EBOV vaccine platforms, the protection conferred correlated with the quantity of EBOV GP-specific Ig produced but not with the production of neutralizing antibodies. 28615211 7 71 theme EBOV 1078:1081 arg1 GPs 1083:1085 EBOV GPs 1078:1085 EBOV GPs that lack GP1 N-linked glycans 1078:1116 As N-linked glycans are thought to shield conserved regions of the EBOV GP receptor-binding domain (RBD), thereby blocking epitopes within the RBD, we also tested whether VSVΔG bearing EBOV GPs that lack GP1 N-linked glycans provided effective immunity against challenge with ma-EBOV or a more distantly related virus, Sudan virus. 28615211 3 72 theme native 525:530 arg1 glycoprotein 534:545 native G glycoprotein 525:545 native G glycoprotein (VSVΔG) 525:553 To expand the vaccine options potentially available, we assessed protection conferred by an EBOV vaccine composed of vesicular stomatitis virus pseudovirions that lack native G glycoprotein (VSVΔG) and bear EBOV glycoprotein (GP). 28615211 3 72 theme native 525:530 arg1 VSVΔG 548:552 VSVΔG 548:552 VSVΔG 548:552 To expand the vaccine options potentially available, we assessed protection conferred by an EBOV vaccine composed of vesicular stomatitis virus pseudovirions that lack native G glycoprotein (VSVΔG) and bear EBOV glycoprotein (GP). 28615211 1 73 theme Ebola 165:169 arg1 EBOV 178:181 EBOV 178:181 EBOV 178:181 The recent Ebola virus (EBOV) epidemic in West Africa demonstrates the potential for a significant public health burden caused by filoviral infections. 28615211 1 73 theme Ebola 165:169 arg1 virus 171:175 The recent Ebola virus 154:175 The recent Ebola virus (EBOV) epidemic in West Africa 154:206 The recent Ebola virus (EBOV) epidemic in West Africa demonstrates the potential for a significant public health burden caused by filoviral infections. 28615211 0 74 theme Virus 50:54 arg1 Glycoprotein 56:67 Ebola Virus Glycoprotein 44:67 Ebola Virus Glycoprotein 44:67 Vesicular Stomatitis Virus Pseudotyped with Ebola Virus Glycoprotein Serves as a Protective, Noninfectious Vaccine against Ebola Virus Challenge in Mice. 28615211 11 75 gly glycoprotein 2170:2181 arg1 glycoprotein 2170:2181 the Ebola virus glycoprotein 2154:2181 the Ebola virus glycoprotein 2154:2181 No FDA-approved vaccines are yet available, but in a trial vaccination strategy in West Africa, recombinant, infectious VSV encoding the Ebola virus glycoprotein effectively prevented virus-associated disease. 28615211 2 76 theme No 306:307 arg1 vaccine 309:315 No vaccine 306:315 No vaccine 306:315 No vaccine or antiviral is currently FDA approved. 28615211 11 77 theme vaccination 2080:2090 arg1 strategy 2092:2099 a trial vaccination strategy 2072:2099 a trial vaccination strategy in West Africa 2072:2114 No FDA-approved vaccines are yet available, but in a trial vaccination strategy in West Africa, recombinant, infectious VSV encoding the Ebola virus glycoprotein effectively prevented virus-associated disease. 28615211 7 78 with challenge 1154:1162 arg1 virus 1205:1209 a more distantly related virus 1180:1209 a more distantly related virus 1180:1209 As N-linked glycans are thought to shield conserved regions of the EBOV GP receptor-binding domain (RBD), thereby blocking epitopes within the RBD, we also tested whether VSVΔG bearing EBOV GPs that lack GP1 N-linked glycans provided effective immunity against challenge with ma-EBOV or a more distantly related virus, Sudan virus. 28615211 7 78 with challenge 1154:1162 arg1 virus 1218:1222 Sudan virus 1212:1222 Sudan virus 1212:1222 As N-linked glycans are thought to shield conserved regions of the EBOV GP receptor-binding domain (RBD), thereby blocking epitopes within the RBD, we also tested whether VSVΔG bearing EBOV GPs that lack GP1 N-linked glycans provided effective immunity against challenge with ma-EBOV or a more distantly related virus, Sudan virus. 28615211 7 78 with challenge 1154:1162 arg1 ma-EBOV 1169:1175 ma-EBOV 1169:1175 ma-EBOV 1169:1175 As N-linked glycans are thought to shield conserved regions of the EBOV GP receptor-binding domain (RBD), thereby blocking epitopes within the RBD, we also tested whether VSVΔG bearing EBOV GPs that lack GP1 N-linked glycans provided effective immunity against challenge with ma-EBOV or a more distantly related virus, Sudan virus. 28615211 10 79 theme Ebola 1936:1940 arg1 virus 1942:1946 The West African Ebola virus epidemic 1919:1955 The West African Ebola virus epidemic 1919:1955 Our results show that EBOV GP/VSVΔG pseudovirions serve as a successful vaccination platform in a rodent model of Ebola virus disease and that GP1 N-glycan loss does not influence immunogenicity or vaccination success.IMPORTANCE The West African Ebola virus epidemic was the largest to date, with more than 28,000 people infected. 28615211 10 79 theme Ebola 1936:1940 arg1 largest 1965:1971 largest 1965:1971 largest 1965:1971 Our results show that EBOV GP/VSVΔG pseudovirions serve as a successful vaccination platform in a rodent model of Ebola virus disease and that GP1 N-glycan loss does not influence immunogenicity or vaccination success.IMPORTANCE The West African Ebola virus epidemic was the largest to date, with more than 28,000 people infected. 28615211 0 80 theme Virus 129:133 arg1 Challenge 135:143 Ebola Virus Challenge 123:143 Ebola Virus Challenge in Mice 123:151 Vesicular Stomatitis Virus Pseudotyped with Ebola Virus Glycoprotein Serves as a Protective, Noninfectious Vaccine against Ebola Virus Challenge in Mice. 28615211 11 81 theme FDA-approved 2024:2035 arg1 vaccines 2037:2044 No FDA-approved vaccines 2021:2044 No FDA-approved vaccines 2021:2044 No FDA-approved vaccines are yet available, but in a trial vaccination strategy in West Africa, recombinant, infectious VSV encoding the Ebola virus glycoprotein effectively prevented virus-associated disease. 28615211 8 82 theme prime/boost 1233:1243 arg1 strategy 1245:1252 a prime/boost strategy 1231:1252 a prime/boost strategy 1231:1252 Using a prime/boost strategy, high doses of GP/VSVΔG partially or fully denuded of N-linked glycans on GP1 protected mice against ma-EBOV challenge, but these mutants were no more effective than wild-type (WT) GP/VSVΔG and did not provide cross protection against Sudan virus. 28615211 10 83 theme West 1923:1926 arg1 virus 1942:1946 The West African Ebola virus epidemic 1919:1955 The West African Ebola virus epidemic 1919:1955 Our results show that EBOV GP/VSVΔG pseudovirions serve as a successful vaccination platform in a rodent model of Ebola virus disease and that GP1 N-glycan loss does not influence immunogenicity or vaccination success.IMPORTANCE The West African Ebola virus epidemic was the largest to date, with more than 28,000 people infected. 28615211 10 83 theme West 1923:1926 arg1 largest 1965:1971 largest 1965:1971 largest 1965:1971 Our results show that EBOV GP/VSVΔG pseudovirions serve as a successful vaccination platform in a rodent model of Ebola virus disease and that GP1 N-glycan loss does not influence immunogenicity or vaccination success.IMPORTANCE The West African Ebola virus epidemic was the largest to date, with more than 28,000 people infected. 28615211 14 84 theme EBOV-challenged 2568:2582 arg1 mice 2584:2587 EBOV-challenged mice 2568:2587 EBOV-challenged mice 2568:2587 We found that wild-type Ebola virus glycoprotein, in the context of this platform, provides robust protection of EBOV-challenged mice. 28615211 9 85 theme neutralizing 1665:1676 arg1 antibodies 1678:1687 neutralizing antibodies 1665:1687 neutralizing antibodies 1665:1687 As reported for other EBOV vaccine platforms, the protection conferred correlated with the quantity of EBOV GP-specific Ig produced but not with the production of neutralizing antibodies. 28615211 4 86 theme single 618:623 arg1 round 625:629 a single round 616:629 a single round of infection 616:642 These pseudovirions mediate a single round of infection. 28615211 5 87 theme single-dose 650:660 arg1 regimens 690:697 Both single-dose and prime/boost vaccination regimens 645:697 Both single-dose and prime/boost vaccination regimens 645:697 Both single-dose and prime/boost vaccination regimens protected mice against lethal challenge with mouse-adapted Ebola virus (ma-EBOV) in a dose-dependent manner. 28615211 10 88 theme vaccination 1762:1772 arg1 platform 1774:1781 a successful vaccination platform 1749:1781 a successful vaccination platform 1749:1781 Our results show that EBOV GP/VSVΔG pseudovirions serve as a successful vaccination platform in a rodent model of Ebola virus disease and that GP1 N-glycan loss does not influence immunogenicity or vaccination success.IMPORTANCE The West African Ebola virus epidemic was the largest to date, with more than 28,000 people infected. 28615211 10 88 theme vaccination 1762:1772 arg1 immunogenicity 1870:1883 immunogenicity 1870:1883 immunogenicity 1870:1883 Our results show that EBOV GP/VSVΔG pseudovirions serve as a successful vaccination platform in a rodent model of Ebola virus disease and that GP1 N-glycan loss does not influence immunogenicity or vaccination success.IMPORTANCE The West African Ebola virus epidemic was the largest to date, with more than 28,000 people infected. 28615211 10 88 theme vaccination 1762:1772 arg1 success.IMPORTANCE 1900:1917 vaccination success.IMPORTANCE 1888:1917 vaccination success.IMPORTANCE 1888:1917 Our results show that EBOV GP/VSVΔG pseudovirions serve as a successful vaccination platform in a rodent model of Ebola virus disease and that GP1 N-glycan loss does not influence immunogenicity or vaccination success.IMPORTANCE The West African Ebola virus epidemic was the largest to date, with more than 28,000 people infected. 28615211 10 88 theme vaccination 1762:1772 arg1 pseudovirions 1726:1738 EBOV GP/VSVΔG pseudovirions 1712:1738 EBOV GP/VSVΔG pseudovirions 1712:1738 Our results show that EBOV GP/VSVΔG pseudovirions serve as a successful vaccination platform in a rodent model of Ebola virus disease and that GP1 N-glycan loss does not influence immunogenicity or vaccination success.IMPORTANCE The West African Ebola virus epidemic was the largest to date, with more than 28,000 people infected. 28615211 5 89 with challenge 729:737 arg1 virus 764:768 mouse-adapted Ebola virus 744:768 mouse-adapted Ebola virus (ma-EBOV) 744:778 Both single-dose and prime/boost vaccination regimens protected mice against lethal challenge with mouse-adapted Ebola virus (ma-EBOV) in a dose-dependent manner. 28615211 5 89 with challenge 729:737 arg1 ma-EBOV 771:777 ma-EBOV 771:777 ma-EBOV 771:777 Both single-dose and prime/boost vaccination regimens protected mice against lethal challenge with mouse-adapted Ebola virus (ma-EBOV) in a dose-dependent manner. 28615211 5 90 theme prime/boost 666:676 arg1 regimens 690:697 Both single-dose and prime/boost vaccination regimens 645:697 Both single-dose and prime/boost vaccination regimens 645:697 Both single-dose and prime/boost vaccination regimens protected mice against lethal challenge with mouse-adapted Ebola virus (ma-EBOV) in a dose-dependent manner. 28615211 1 91 from epidemic 184:191 arg1 Africa 201:206 Africa 201:206 Africa 201:206 The recent Ebola virus (EBOV) epidemic in West Africa demonstrates the potential for a significant public health burden caused by filoviral infections. 28615211 8 92 theme GP/VSVΔG 1269:1276 arg1 doses 1260:1264 high doses 1255:1264 high doses of GP/VSVΔG partially or fully denuded of N-linked glycans on GP1 1255:1330 Using a prime/boost strategy, high doses of GP/VSVΔG partially or fully denuded of N-linked glycans on GP1 protected mice against ma-EBOV challenge, but these mutants were no more effective than wild-type (WT) GP/VSVΔG and did not provide cross protection against Sudan virus. 28615211 5 93 theme Ebola 758:762 arg1 virus 764:768 mouse-adapted Ebola virus 744:768 mouse-adapted Ebola virus (ma-EBOV) 744:778 Both single-dose and prime/boost vaccination regimens protected mice against lethal challenge with mouse-adapted Ebola virus (ma-EBOV) in a dose-dependent manner. 28615211 5 93 theme Ebola 758:762 arg1 ma-EBOV 771:777 ma-EBOV 771:777 ma-EBOV 771:777 Both single-dose and prime/boost vaccination regimens protected mice against lethal challenge with mouse-adapted Ebola virus (ma-EBOV) in a dose-dependent manner. 28615211 10 94 theme rodent 1788:1793 arg1 model 1795:1799 a rodent model 1786:1799 a rodent model of Ebola virus disease 1786:1822 Our results show that EBOV GP/VSVΔG pseudovirions serve as a successful vaccination platform in a rodent model of Ebola virus disease and that GP1 N-glycan loss does not influence immunogenicity or vaccination success.IMPORTANCE The West African Ebola virus epidemic was the largest to date, with more than 28,000 people infected. 28615211 14 95 theme platform 2528:2535 arg1 context 2512:2518 the context 2508:2518 the context of this platform 2508:2535 We found that wild-type Ebola virus glycoprotein, in the context of this platform, provides robust protection of EBOV-challenged mice. 28615211 3 96 gly glycoprotein 534:545 arg1 glycoprotein 534:545 native G glycoprotein 525:545 native G glycoprotein (VSVΔG) 525:553 To expand the vaccine options potentially available, we assessed protection conferred by an EBOV vaccine composed of vesicular stomatitis virus pseudovirions that lack native G glycoprotein (VSVΔG) and bear EBOV glycoprotein (GP). 28615211 3 96 gly glycoprotein 534:545 arg1 VSVΔG 548:552 VSVΔG 548:552 VSVΔG 548:552 To expand the vaccine options potentially available, we assessed protection conferred by an EBOV vaccine composed of vesicular stomatitis virus pseudovirions that lack native G glycoprotein (VSVΔG) and bear EBOV glycoprotein (GP). 28615211 0 97 theme Protective 81:90 arg1 Virus 21:25 Vesicular Stomatitis Virus 0:25 Vesicular Stomatitis Virus Pseudotyped with Ebola Virus Glycoprotein 0:67 Vesicular Stomatitis Virus Pseudotyped with Ebola Virus Glycoprotein Serves as a Protective, Noninfectious Vaccine against Ebola Virus Challenge in Mice. 28615211 0 97 theme Protective 81:90 arg1 Vaccine 107:113 a Protective, Noninfectious Vaccine 79:113 a Protective, Noninfectious Vaccine against Ebola Virus Challenge in Mice 79:151 Vesicular Stomatitis Virus Pseudotyped with Ebola Virus Glycoprotein Serves as a Protective, Noninfectious Vaccine against Ebola Virus Challenge in Mice. 28615211 11 98 from strategy 2092:2099 arg1 Africa 2109:2114 Africa 2109:2114 Africa 2109:2114 No FDA-approved vaccines are yet available, but in a trial vaccination strategy in West Africa, recombinant, infectious VSV encoding the Ebola virus glycoprotein effectively prevented virus-associated disease. 28615211 11 99 theme Ebola 2158:2162 arg1 glycoprotein 2170:2181 the Ebola virus glycoprotein 2154:2181 the Ebola virus glycoprotein 2154:2181 No FDA-approved vaccines are yet available, but in a trial vaccination strategy in West Africa, recombinant, infectious VSV encoding the Ebola virus glycoprotein effectively prevented virus-associated disease. 28615211 8 100 theme cross 1464:1468 arg1 protection 1470:1479 cross protection 1464:1479 cross protection against Sudan virus 1464:1499 Using a prime/boost strategy, high doses of GP/VSVΔG partially or fully denuded of N-linked glycans on GP1 protected mice against ma-EBOV challenge, but these mutants were no more effective than wild-type (WT) GP/VSVΔG and did not provide cross protection against Sudan virus. 28615211 5 101 theme lethal 722:727 arg1 challenge 729:737 lethal challenge 722:737 lethal challenge with mouse-adapted Ebola virus (ma-EBOV) 722:778 Both single-dose and prime/boost vaccination regimens protected mice against lethal challenge with mouse-adapted Ebola virus (ma-EBOV) in a dose-dependent manner. 28615211 7 102 theme receptor-binding 968:983 arg1 RBD 993:995 RBD 993:995 RBD 993:995 As N-linked glycans are thought to shield conserved regions of the EBOV GP receptor-binding domain (RBD), thereby blocking epitopes within the RBD, we also tested whether VSVΔG bearing EBOV GPs that lack GP1 N-linked glycans provided effective immunity against challenge with ma-EBOV or a more distantly related virus, Sudan virus. 28615211 7 102 theme receptor-binding 968:983 arg1 domain 985:990 the EBOV GP receptor-binding domain 956:990 the EBOV GP receptor-binding domain (RBD) 956:996 As N-linked glycans are thought to shield conserved regions of the EBOV GP receptor-binding domain (RBD), thereby blocking epitopes within the RBD, we also tested whether VSVΔG bearing EBOV GPs that lack GP1 N-linked glycans provided effective immunity against challenge with ma-EBOV or a more distantly related virus, Sudan virus. 28615211 12 103 theme VSVΔG 2231:2235 arg1 vaccines 2250:2257 VSVΔG pseudovirion vaccines 2231:2257 VSVΔG pseudovirion vaccines 2231:2257 VSVΔG pseudovirion vaccines may prove as efficacious and have better safety, but they have not been tested to date. 28615211 11 104 dep recombinant 2117:2127 arg1 infectious 2130:2139 infectious 2130:2139 infectious 2130:2139 No FDA-approved vaccines are yet available, but in a trial vaccination strategy in West Africa, recombinant, infectious VSV encoding the Ebola virus glycoprotein effectively prevented virus-associated disease. 28615211 8 105 theme N-linked 1308:1315 arg1 glycans 1317:1323 N-linked glycans 1308:1323 N-linked glycans 1308:1323 Using a prime/boost strategy, high doses of GP/VSVΔG partially or fully denuded of N-linked glycans on GP1 protected mice against ma-EBOV challenge, but these mutants were no more effective than wild-type (WT) GP/VSVΔG and did not provide cross protection against Sudan virus. 28615211 7 106 theme EBOV 960:963 arg1 RBD 993:995 RBD 993:995 RBD 993:995 As N-linked glycans are thought to shield conserved regions of the EBOV GP receptor-binding domain (RBD), thereby blocking epitopes within the RBD, we also tested whether VSVΔG bearing EBOV GPs that lack GP1 N-linked glycans provided effective immunity against challenge with ma-EBOV or a more distantly related virus, Sudan virus. 28615211 7 106 theme EBOV 960:963 arg1 domain 985:990 the EBOV GP receptor-binding domain 956:990 the EBOV GP receptor-binding domain (RBD) 956:996 As N-linked glycans are thought to shield conserved regions of the EBOV GP receptor-binding domain (RBD), thereby blocking epitopes within the RBD, we also tested whether VSVΔG bearing EBOV GPs that lack GP1 N-linked glycans provided effective immunity against challenge with ma-EBOV or a more distantly related virus, Sudan virus. 28615211 13 107 theme pseudovirions 2385:2397 arg1 efficacy 2367:2374 the efficacy 2363:2374 the efficacy of VSVΔG pseudovirions bearing Ebola virus glycoprotein as a vaccine platform 2363:2452 Thus, we tested the efficacy of VSVΔG pseudovirions bearing Ebola virus glycoprotein as a vaccine platform. 28615211 10 108 dep virus 1942:1946 arg1 epidemic 1948:1955 epidemic 1948:1955 epidemic 1948:1955 Our results show that EBOV GP/VSVΔG pseudovirions serve as a successful vaccination platform in a rodent model of Ebola virus disease and that GP1 N-glycan loss does not influence immunogenicity or vaccination success.IMPORTANCE The West African Ebola virus epidemic was the largest to date, with more than 28,000 people infected. 28615211 13 109 theme vaccine 2437:2443 arg1 glycoprotein 2419:2430 Ebola virus glycoprotein 2407:2430 Ebola virus glycoprotein 2407:2430 Thus, we tested the efficacy of VSVΔG pseudovirions bearing Ebola virus glycoprotein as a vaccine platform. 28615211 13 109 theme vaccine 2437:2443 arg1 platform 2445:2452 a vaccine platform 2435:2452 a vaccine platform 2435:2452 Thus, we tested the efficacy of VSVΔG pseudovirions bearing Ebola virus glycoprotein as a vaccine platform. 28615211 0 110 theme Stomatitis 10:19 arg1 Virus 21:25 Vesicular Stomatitis Virus 0:25 Vesicular Stomatitis Virus Pseudotyped with Ebola Virus Glycoprotein 0:67 Vesicular Stomatitis Virus Pseudotyped with Ebola Virus Glycoprotein Serves as a Protective, Noninfectious Vaccine against Ebola Virus Challenge in Mice. 28615211 0 110 theme Stomatitis 10:19 arg1 Vaccine 107:113 a Protective, Noninfectious Vaccine 79:113 a Protective, Noninfectious Vaccine against Ebola Virus Challenge in Mice 79:151 Vesicular Stomatitis Virus Pseudotyped with Ebola Virus Glycoprotein Serves as a Protective, Noninfectious Vaccine against Ebola Virus Challenge in Mice. 28615211 14 111 theme mice 2584:2587 arg1 protection 2554:2563 robust protection 2547:2563 robust protection of EBOV-challenged mice 2547:2587 We found that wild-type Ebola virus glycoprotein, in the context of this platform, provides robust protection of EBOV-challenged mice. 28615211 0 112 dep Protective 81:90 arg1 Noninfectious 93:105 Noninfectious 93:105 Noninfectious 93:105 Vesicular Stomatitis Virus Pseudotyped with Ebola Virus Glycoprotein Serves as a Protective, Noninfectious Vaccine against Ebola Virus Challenge in Mice. 28615211 3 113 theme vaccine 371:377 arg1 options 379:385 the vaccine options 367:385 the vaccine options potentially available 367:407 To expand the vaccine options potentially available, we assessed protection conferred by an EBOV vaccine composed of vesicular stomatitis virus pseudovirions that lack native G glycoprotein (VSVΔG) and bear EBOV glycoprotein (GP). 28615211 7 114 theme conserved 935:943 arg1 regions 945:951 conserved regions 935:951 conserved regions of the EBOV GP receptor-binding domain (RBD) 935:996 As N-linked glycans are thought to shield conserved regions of the EBOV GP receptor-binding domain (RBD), thereby blocking epitopes within the RBD, we also tested whether VSVΔG bearing EBOV GPs that lack GP1 N-linked glycans provided effective immunity against challenge with ma-EBOV or a more distantly related virus, Sudan virus. 28615211 9 115 theme vaccine 1529:1535 arg1 platforms 1537:1545 other EBOV vaccine platforms 1518:1545 other EBOV vaccine platforms 1518:1545 As reported for other EBOV vaccine platforms, the protection conferred correlated with the quantity of EBOV GP-specific Ig produced but not with the production of neutralizing antibodies. 28615211 7 116 theme effective 1127:1135 arg1 immunity 1137:1144 effective immunity 1127:1144 effective immunity against challenge with ma-EBOV or a more distantly related virus, Sudan virus 1127:1222 As N-linked glycans are thought to shield conserved regions of the EBOV GP receptor-binding domain (RBD), thereby blocking epitopes within the RBD, we also tested whether VSVΔG bearing EBOV GPs that lack GP1 N-linked glycans provided effective immunity against challenge with ma-EBOV or a more distantly related virus, Sudan virus. 28615211 3 117 gly glycoprotein 569:580 arg1 GP 583:584 GP 583:584 GP 583:584 To expand the vaccine options potentially available, we assessed protection conferred by an EBOV vaccine composed of vesicular stomatitis virus pseudovirions that lack native G glycoprotein (VSVΔG) and bear EBOV glycoprotein (GP). 28615211 3 117 gly glycoprotein 569:580 arg1 glycoprotein 569:580 bear EBOV glycoprotein 559:580 bear EBOV glycoprotein (GP) 559:585 To expand the vaccine options potentially available, we assessed protection conferred by an EBOV vaccine composed of vesicular stomatitis virus pseudovirions that lack native G glycoprotein (VSVΔG) and bear EBOV glycoprotein (GP). 28615211 12 118 contain have 2288:2291 arg1 vaccines 2250:2257 VSVΔG pseudovirion vaccines 2231:2257 VSVΔG pseudovirion vaccines 2231:2257 VSVΔG pseudovirion vaccines may prove as efficacious and have better safety, but they have not been tested to date. 28615211 12 118 contain have 2288:2291 arg2 safety 2300:2305 better safety 2293:2305 better safety 2293:2305 VSVΔG pseudovirion vaccines may prove as efficacious and have better safety, but they have not been tested to date. 28615211 15 119 theme heavy 2628:2632 arg1 regions 2670:2676 the heavy glycan shield surrounding conserved regions 2624:2676 the heavy glycan shield surrounding conserved regions of the glycoprotein 2624:2696 Further, we found that removal of the heavy glycan shield surrounding conserved regions of the glycoprotein does not enhance vaccine efficacy. 28615211 10 120 theme virus 1810:1814 arg1 disease 1816:1822 Ebola virus disease 1804:1822 Ebola virus disease 1804:1822 Our results show that EBOV GP/VSVΔG pseudovirions serve as a successful vaccination platform in a rodent model of Ebola virus disease and that GP1 N-glycan loss does not influence immunogenicity or vaccination success.IMPORTANCE The West African Ebola virus epidemic was the largest to date, with more than 28,000 people infected. 28615211 7 121 link N-linked 1101:1108 arg1 glycans 1110:1116 GP1 N-linked glycans 1097:1116 GP1 N-linked glycans 1097:1116 As N-linked glycans are thought to shield conserved regions of the EBOV GP receptor-binding domain (RBD), thereby blocking epitopes within the RBD, we also tested whether VSVΔG bearing EBOV GPs that lack GP1 N-linked glycans provided effective immunity against challenge with ma-EBOV or a more distantly related virus, Sudan virus. 28615211 15 122 theme shield 2641:2646 arg1 regions 2670:2676 the heavy glycan shield surrounding conserved regions 2624:2676 the heavy glycan shield surrounding conserved regions of the glycoprotein 2624:2696 Further, we found that removal of the heavy glycan shield surrounding conserved regions of the glycoprotein does not enhance vaccine efficacy. 28615211 8 123 dep wild-type 1420:1428 arg1 WT 1431:1432 WT 1431:1432 WT 1431:1432 Using a prime/boost strategy, high doses of GP/VSVΔG partially or fully denuded of N-linked glycans on GP1 protected mice against ma-EBOV challenge, but these mutants were no more effective than wild-type (WT) GP/VSVΔG and did not provide cross protection against Sudan virus. 28615211 14 124 theme Ebola 2479:2483 arg1 glycoprotein 2491:2502 wild-type Ebola virus glycoprotein 2469:2502 wild-type Ebola virus glycoprotein 2469:2502 We found that wild-type Ebola virus glycoprotein, in the context of this platform, provides robust protection of EBOV-challenged mice. 28615211 10 125 dep immunogenicity 1870:1883 arg1 virus 1942:1946 The West African Ebola virus epidemic 1919:1955 The West African Ebola virus epidemic 1919:1955 Our results show that EBOV GP/VSVΔG pseudovirions serve as a successful vaccination platform in a rodent model of Ebola virus disease and that GP1 N-glycan loss does not influence immunogenicity or vaccination success.IMPORTANCE The West African Ebola virus epidemic was the largest to date, with more than 28,000 people infected. 28615211 10 125 dep immunogenicity 1870:1883 arg1 largest 1965:1971 largest 1965:1971 largest 1965:1971 Our results show that EBOV GP/VSVΔG pseudovirions serve as a successful vaccination platform in a rodent model of Ebola virus disease and that GP1 N-glycan loss does not influence immunogenicity or vaccination success.IMPORTANCE The West African Ebola virus epidemic was the largest to date, with more than 28,000 people infected. 28615211 3 126 theme stomatitis 484:493 arg1 virus 495:499 vesicular stomatitis virus 474:499 vesicular stomatitis virus pseudovirions that lack native G glycoprotein (VSVΔG) and bear EBOV glycoprotein (GP) 474:585 To expand the vaccine options potentially available, we assessed protection conferred by an EBOV vaccine composed of vesicular stomatitis virus pseudovirions that lack native G glycoprotein (VSVΔG) and bear EBOV glycoprotein (GP). 28615211 10 127 theme GP1 1833:1835 arg1 loss 1846:1849 GP1 N-glycan loss 1833:1849 GP1 N-glycan loss 1833:1849 Our results show that EBOV GP/VSVΔG pseudovirions serve as a successful vaccination platform in a rodent model of Ebola virus disease and that GP1 N-glycan loss does not influence immunogenicity or vaccination success.IMPORTANCE The West African Ebola virus epidemic was the largest to date, with more than 28,000 people infected. 28615211 15 128 gly glycoprotein 2685:2696 arg1 glycoprotein 2685:2696 the glycoprotein 2681:2696 the glycoprotein 2681:2696 Further, we found that removal of the heavy glycan shield surrounding conserved regions of the glycoprotein does not enhance vaccine efficacy. 28615211 10 129 theme infected 2011:2018 arg1 people 2004:2009 more than 28,000 people infected 1987:2018 more than 28,000 people infected 1987:2018 Our results show that EBOV GP/VSVΔG pseudovirions serve as a successful vaccination platform in a rodent model of Ebola virus disease and that GP1 N-glycan loss does not influence immunogenicity or vaccination success.IMPORTANCE The West African Ebola virus epidemic was the largest to date, with more than 28,000 people infected. 28615211 15 130 theme glycoprotein 2685:2696 arg1 regions 2670:2676 the heavy glycan shield surrounding conserved regions 2624:2676 the heavy glycan shield surrounding conserved regions of the glycoprotein 2624:2696 Further, we found that removal of the heavy glycan shield surrounding conserved regions of the glycoprotein does not enhance vaccine efficacy. 28715446 0 0 theme cell 94:97 arg1 apoptosis 99:107 free fatty acid-induced β cell apoptosis 68:107 free fatty acid-induced β cell apoptosis 68:107 Active subfractions of Abelmoschus esculentus substantially prevent free fatty acid-induced β cell apoptosis via inhibiting dipeptidyl peptidase-4. 28715446 6 1 theme pentacyclic 886:896 arg1 ester 909:913 pentacyclic triterpene ester 886:913 pentacyclic triterpene ester 886:913 Among them F1 (rich in quercetin glucosides and pentacyclic triterpene ester) and F2 (containing large amounts of carbohydrates and polysaccharides) were found to be especially effective in attenuating DPP-4 signaling, and to have the potential to counter diabetic nephropathy. 28715446 0 2 theme β 92:92 arg1 apoptosis 99:107 free fatty acid-induced β cell apoptosis 68:107 free fatty acid-induced β cell apoptosis 68:107 Active subfractions of Abelmoschus esculentus substantially prevent free fatty acid-induced β cell apoptosis via inhibiting dipeptidyl peptidase-4. 28715446 6 3 theme polysaccharides 970:984 arg1 polysaccharides 970:984 polysaccharides 970:984 polysaccharides 970:984 Among them F1 (rich in quercetin glucosides and pentacyclic triterpene ester) and F2 (containing large amounts of carbohydrates and polysaccharides) were found to be especially effective in attenuating DPP-4 signaling, and to have the potential to counter diabetic nephropathy. 28715446 6 3 theme polysaccharides 970:984 arg1 carbohydrates 952:964 carbohydrates 952:964 carbohydrates 952:964 Among them F1 (rich in quercetin glucosides and pentacyclic triterpene ester) and F2 (containing large amounts of carbohydrates and polysaccharides) were found to be especially effective in attenuating DPP-4 signaling, and to have the potential to counter diabetic nephropathy. 28715446 6 3 theme polysaccharides 970:984 arg1 amounts 941:947 large amounts 935:947 large amounts of carbohydrates and polysaccharides 935:984 Among them F1 (rich in quercetin glucosides and pentacyclic triterpene ester) and F2 (containing large amounts of carbohydrates and polysaccharides) were found to be especially effective in attenuating DPP-4 signaling, and to have the potential to counter diabetic nephropathy. 28715446 1 4 theme β 259:259 arg1 cells 261:265 β cells 259:265 β cells 259:265 Lipotoxicity plays an important role in exacerbating type 2 diabetes mellitus (T2DM) and leads to apoptosis of β cells. 28715446 12 5 theme mitochondrial 1853:1865 arg1 pathways 1867:1874 mitochondrial pathways 1853:1874 mitochondrial pathways 1853:1874 In addition, AMPK/mTOR, PI3K and mitochondrial pathways were regulated by AE, and this attenuated the palmitate-induced signaling cascades. 28715446 7 6 theme β 1242:1242 arg1 cells 1244:1248 β cells 1242:1248 β cells 1242:1248 Hence, the aim of the present study was to investigate whether AE subfractions can prevent the palmitate-induced apoptosis of β cells, and the putative signals involved. 28715446 1 7 theme cells 261:265 arg1 apoptosis 246:254 apoptosis 246:254 apoptosis of β cells 246:265 Lipotoxicity plays an important role in exacerbating type 2 diabetes mellitus (T2DM) and leads to apoptosis of β cells. 28715446 8 8 theme flow 1391:1394 arg1 cytometry 1396:1404 flow cytometry 1391:1404 flow cytometry 1391:1404 We demonstrated that AE, and especially 1 μg/mL of F2, decreased palmitate-induced apoptosis analyzed by flow cytometry. 28715446 5 9 from AE 790:791 arg1 subfractions 772:783 subfractions 772:783 subfractions from AE, each with its own composition and property 772:835 In our recent report, a sequence of extraction steps was used to obtain a series of subfractions from AE, each with its own composition and property. 28715446 5 9 from AE 790:791 arg1 series 762:767 a series 760:767 a series of subfractions from AE, each with its own composition and property 760:835 In our recent report, a sequence of extraction steps was used to obtain a series of subfractions from AE, each with its own composition and property. 28715446 2 10 theme peptidase-4 288:298 arg1 inhibitors 308:317 dipeptidyl peptidase-4 (DPP-4) inhibitors 277:317 dipeptidyl peptidase-4 (DPP-4) inhibitors 277:317 Recently dipeptidyl peptidase-4 (DPP-4) inhibitors have emerged as a useful tool in the treatment of T2DM. 28715446 10 11 theme inhibitor 1545:1553 arg1 linagliptin 1555:1565 The DPP-4 inhibitor linagliptin 1535:1565 The DPP-4 inhibitor linagliptin 1535:1565 The DPP-4 inhibitor linagliptin decreased the expression of caspase 3, suggesting that DPP-4 is critically involved in apoptotic signaling. 28715446 0 12 theme dipeptidyl 124:133 arg1 peptidase-4 135:145 dipeptidyl peptidase-4 124:145 dipeptidyl peptidase-4 124:145 Active subfractions of Abelmoschus esculentus substantially prevent free fatty acid-induced β cell apoptosis via inhibiting dipeptidyl peptidase-4. 28715446 7 13 theme study 1146:1150 arg1 aim 1127:1129 the aim 1123:1129 the aim of the present study 1123:1150 Hence, the aim of the present study was to investigate whether AE subfractions can prevent the palmitate-induced apoptosis of β cells, and the putative signals involved. 28715446 7 14 theme AE 1179:1180 arg1 subfractions 1182:1193 AE subfractions 1179:1193 AE subfractions 1179:1193 Hence, the aim of the present study was to investigate whether AE subfractions can prevent the palmitate-induced apoptosis of β cells, and the putative signals involved. 28715446 2 15 theme dipeptidyl 277:286 arg1 peptidase-4 288:298 dipeptidyl peptidase-4 277:298 dipeptidyl peptidase-4 (DPP-4) inhibitors 277:317 Recently dipeptidyl peptidase-4 (DPP-4) inhibitors have emerged as a useful tool in the treatment of T2DM. 28715446 2 15 theme dipeptidyl 277:286 arg1 DPP-4 301:305 DPP-4 301:305 DPP-4 301:305 Recently dipeptidyl peptidase-4 (DPP-4) inhibitors have emerged as a useful tool in the treatment of T2DM. 28715446 5 16 theme subfractions 772:783 arg1 series 762:767 a series 760:767 a series of subfractions from AE, each with its own composition and property 760:835 In our recent report, a sequence of extraction steps was used to obtain a series of subfractions from AE, each with its own composition and property. 28715446 9 17 theme western 1421:1427 arg1 blot 1429:1432 western blot 1421:1432 western blot 1421:1432 The result of western blot revealed that palmitate-induced decrease in GLP-1R and increase in DPP-4 were restored by F1 and F2. 28715446 13 18 theme β 2019:2019 arg1 apoptosis 2026:2034 β cell apoptosis 2019:2034 β cell apoptosis 2019:2034 In conclusion, AE is useful to prevent the exacerbation of β cell apoptosis, and it could potentially be used as adjuvant or nutraceutical therapy for diabetes. 28715446 6 19 contain containing 924:933 arg2 polysaccharides 970:984 polysaccharides 970:984 polysaccharides 970:984 Among them F1 (rich in quercetin glucosides and pentacyclic triterpene ester) and F2 (containing large amounts of carbohydrates and polysaccharides) were found to be especially effective in attenuating DPP-4 signaling, and to have the potential to counter diabetic nephropathy. 28715446 6 19 contain containing 924:933 arg1 F2 920:921 F2 920:921 F2 (containing large amounts of carbohydrates and polysaccharides) 920:985 Among them F1 (rich in quercetin glucosides and pentacyclic triterpene ester) and F2 (containing large amounts of carbohydrates and polysaccharides) were found to be especially effective in attenuating DPP-4 signaling, and to have the potential to counter diabetic nephropathy. 28715446 6 19 contain containing 924:933 arg2 carbohydrates 952:964 carbohydrates 952:964 carbohydrates 952:964 Among them F1 (rich in quercetin glucosides and pentacyclic triterpene ester) and F2 (containing large amounts of carbohydrates and polysaccharides) were found to be especially effective in attenuating DPP-4 signaling, and to have the potential to counter diabetic nephropathy. 28715446 6 19 contain containing 924:933 arg2 amounts 941:947 large amounts 935:947 large amounts of carbohydrates and polysaccharides 935:984 Among them F1 (rich in quercetin glucosides and pentacyclic triterpene ester) and F2 (containing large amounts of carbohydrates and polysaccharides) were found to be especially effective in attenuating DPP-4 signaling, and to have the potential to counter diabetic nephropathy. 28715446 6 20 from quercetin 861:869 arg1 rich 853:856 rich 853:856 rich 853:856 Among them F1 (rich in quercetin glucosides and pentacyclic triterpene ester) and F2 (containing large amounts of carbohydrates and polysaccharides) were found to be especially effective in attenuating DPP-4 signaling, and to have the potential to counter diabetic nephropathy. 28715446 3 21 theme β 492:492 arg1 cells 494:498 β cells 492:498 β cells 492:498 DPP-4 degrades type 1 glucagon-like peptide (GLP-1), and GLP-1 receptor (GLP-1R) signaling has been shown to protect β cells by modulating AMPK/mTOR, PI3K, and Bax. 28715446 9 22 from increase 1489:1496 arg1 GLP-1R 1478:1483 GLP-1R 1478:1483 GLP-1R 1478:1483 The result of western blot revealed that palmitate-induced decrease in GLP-1R and increase in DPP-4 were restored by F1 and F2. 28715446 9 22 from increase 1489:1496 arg1 DPP-4 1501:1505 DPP-4 1501:1505 DPP-4 1501:1505 The result of western blot revealed that palmitate-induced decrease in GLP-1R and increase in DPP-4 were restored by F1 and F2. 28715446 1 23 theme type 201:204 arg1 T2DM 227:230 T2DM 227:230 T2DM 227:230 Lipotoxicity plays an important role in exacerbating type 2 diabetes mellitus (T2DM) and leads to apoptosis of β cells. 28715446 1 23 theme type 201:204 arg1 mellitus 217:224 type 2 diabetes mellitus 201:224 type 2 diabetes mellitus (T2DM) 201:231 Lipotoxicity plays an important role in exacerbating type 2 diabetes mellitus (T2DM) and leads to apoptosis of β cells. 28715446 5 24 theme recent 695:700 arg1 report 702:707 our recent report 691:707 our recent report 691:707 In our recent report, a sequence of extraction steps was used to obtain a series of subfractions from AE, each with its own composition and property. 28715446 2 25 from tool 344:347 arg1 treatment 356:364 the treatment 352:364 the treatment of T2DM 352:372 Recently dipeptidyl peptidase-4 (DPP-4) inhibitors have emerged as a useful tool in the treatment of T2DM. 28715446 9 26 theme blot 1429:1432 arg1 result 1411:1416 The result 1407:1416 The result of western blot 1407:1432 The result of western blot revealed that palmitate-induced decrease in GLP-1R and increase in DPP-4 were restored by F1 and F2. 28715446 13 27 from conclusion 1963:1972 arg1 useful 1981:1986 useful 1981:1986 useful 1981:1986 In conclusion, AE is useful to prevent the exacerbation of β cell apoptosis, and it could potentially be used as adjuvant or nutraceutical therapy for diabetes. 28715446 2 28 theme T2DM 369:372 arg1 treatment 356:364 the treatment 352:364 the treatment of T2DM 352:372 Recently dipeptidyl peptidase-4 (DPP-4) inhibitors have emerged as a useful tool in the treatment of T2DM. 28715446 0 29 theme Active 0:5 arg1 subfractions 7:18 Active subfractions 0:18 Active subfractions of Abelmoschus esculentus 0:44 Active subfractions of Abelmoschus esculentus substantially prevent free fatty acid-induced β cell apoptosis via inhibiting dipeptidyl peptidase-4. 28715446 13 30 used used 2065:2068 arg2 it 2041:2042 it 2041:2042 it 2041:2042 In conclusion, AE is useful to prevent the exacerbation of β cell apoptosis, and it could potentially be used as adjuvant or nutraceutical therapy for diabetes. 28715446 13 30 used used 2065:2068 arg2 therapy 2099:2105 adjuvant or nutraceutical therapy 2073:2105 adjuvant or nutraceutical therapy for diabetes 2073:2118 In conclusion, AE is useful to prevent the exacerbation of β cell apoptosis, and it could potentially be used as adjuvant or nutraceutical therapy for diabetes. 28715446 6 31 theme DPP-4 1040:1044 arg1 signaling 1046:1054 DPP-4 signaling 1040:1054 DPP-4 signaling 1040:1054 Among them F1 (rich in quercetin glucosides and pentacyclic triterpene ester) and F2 (containing large amounts of carbohydrates and polysaccharides) were found to be especially effective in attenuating DPP-4 signaling, and to have the potential to counter diabetic nephropathy. 28715446 1 32 theme diabetes 208:215 arg1 T2DM 227:230 T2DM 227:230 T2DM 227:230 Lipotoxicity plays an important role in exacerbating type 2 diabetes mellitus (T2DM) and leads to apoptosis of β cells. 28715446 1 32 theme diabetes 208:215 arg1 mellitus 217:224 type 2 diabetes mellitus 201:224 type 2 diabetes mellitus (T2DM) 201:231 Lipotoxicity plays an important role in exacerbating type 2 diabetes mellitus (T2DM) and leads to apoptosis of β cells. 28715446 5 33 theme steps 735:739 arg1 sequence 712:719 a sequence 710:719 a sequence of extraction steps 710:739 In our recent report, a sequence of extraction steps was used to obtain a series of subfractions from AE, each with its own composition and property. 28715446 5 34 theme extraction 724:733 arg1 steps 735:739 extraction steps 724:739 extraction steps 724:739 In our recent report, a sequence of extraction steps was used to obtain a series of subfractions from AE, each with its own composition and property. 28715446 10 35 theme apoptotic 1654:1662 arg1 signaling 1664:1672 apoptotic signaling 1654:1672 apoptotic signaling 1654:1672 The DPP-4 inhibitor linagliptin decreased the expression of caspase 3, suggesting that DPP-4 is critically involved in apoptotic signaling. 28715446 7 36 theme putative 1259:1266 arg1 signals 1268:1274 the putative signals 1255:1274 the putative signals involved 1255:1283 Hence, the aim of the present study was to investigate whether AE subfractions can prevent the palmitate-induced apoptosis of β cells, and the putative signals involved. 28715446 4 37 theme esculentus 585:594 arg1 effect 563:568 The anti-hyperglycemic effect 540:568 The anti-hyperglycemic effect of Abelmoschus esculentus (AE) 540:599 The anti-hyperglycemic effect of Abelmoschus esculentus (AE) is well known, however its mucilage makes it difficult to further examine this effect. 28715446 13 38 theme adjuvant 2073:2080 arg1 it 2041:2042 it 2041:2042 it 2041:2042 In conclusion, AE is useful to prevent the exacerbation of β cell apoptosis, and it could potentially be used as adjuvant or nutraceutical therapy for diabetes. 28715446 13 38 theme adjuvant 2073:2080 arg1 therapy 2099:2105 adjuvant or nutraceutical therapy 2073:2105 adjuvant or nutraceutical therapy for diabetes 2073:2118 In conclusion, AE is useful to prevent the exacerbation of β cell apoptosis, and it could potentially be used as adjuvant or nutraceutical therapy for diabetes. 28715446 9 39 theme palmitate-induced 1448:1464 arg1 decrease 1466:1473 palmitate-induced decrease 1448:1473 palmitate-induced decrease in GLP-1R 1448:1483 The result of western blot revealed that palmitate-induced decrease in GLP-1R and increase in DPP-4 were restored by F1 and F2. 28715446 9 40 from decrease 1466:1473 arg1 GLP-1R 1478:1483 GLP-1R 1478:1483 GLP-1R 1478:1483 The result of western blot revealed that palmitate-induced decrease in GLP-1R and increase in DPP-4 were restored by F1 and F2. 28715446 9 40 from decrease 1466:1473 arg1 DPP-4 1501:1505 DPP-4 1501:1505 DPP-4 1501:1505 The result of western blot revealed that palmitate-induced decrease in GLP-1R and increase in DPP-4 were restored by F1 and F2. 28715446 3 41 theme receptor 438:445 arg1 signaling 456:464 GLP-1 receptor (GLP-1R) signaling 432:464 GLP-1 receptor (GLP-1R) signaling 432:464 DPP-4 degrades type 1 glucagon-like peptide (GLP-1), and GLP-1 receptor (GLP-1R) signaling has been shown to protect β cells by modulating AMPK/mTOR, PI3K, and Bax. 28715446 6 42 from rich 853:856 arg1 quercetin 861:869 quercetin 861:869 quercetin 861:869 Among them F1 (rich in quercetin glucosides and pentacyclic triterpene ester) and F2 (containing large amounts of carbohydrates and polysaccharides) were found to be especially effective in attenuating DPP-4 signaling, and to have the potential to counter diabetic nephropathy. 28715446 12 43 theme palmitate-induced 1922:1938 arg1 cascades 1950:1957 the palmitate-induced signaling cascades 1918:1957 the palmitate-induced signaling cascades 1918:1957 In addition, AMPK/mTOR, PI3K and mitochondrial pathways were regulated by AE, and this attenuated the palmitate-induced signaling cascades. 28715446 10 44 theme DPP-4 1539:1543 arg1 linagliptin 1555:1565 The DPP-4 inhibitor linagliptin 1535:1565 The DPP-4 inhibitor linagliptin 1535:1565 The DPP-4 inhibitor linagliptin decreased the expression of caspase 3, suggesting that DPP-4 is critically involved in apoptotic signaling. 28715446 0 45 theme esculentus 35:44 arg1 subfractions 7:18 Active subfractions 0:18 Active subfractions of Abelmoschus esculentus 0:44 Active subfractions of Abelmoschus esculentus substantially prevent free fatty acid-induced β cell apoptosis via inhibiting dipeptidyl peptidase-4. 28715446 11 46 theme activity 1694:1701 arg1 Analysis 1675:1682 Analysis 1675:1682 Analysis of enzyme activity 1675:1701 Analysis of enzyme activity revealed that palmitate increased the activity of DPP4 nearly 2 folds, while F2 especially inhibited the activation. 28715446 3 47 theme glucagon-like 397:409 arg1 GLP-1 420:424 GLP-1 420:424 GLP-1 420:424 DPP-4 degrades type 1 glucagon-like peptide (GLP-1), and GLP-1 receptor (GLP-1R) signaling has been shown to protect β cells by modulating AMPK/mTOR, PI3K, and Bax. 28715446 3 47 theme glucagon-like 397:409 arg1 peptide 411:417 type 1 glucagon-like peptide 390:417 type 1 glucagon-like peptide (GLP-1) 390:425 DPP-4 degrades type 1 glucagon-like peptide (GLP-1), and GLP-1 receptor (GLP-1R) signaling has been shown to protect β cells by modulating AMPK/mTOR, PI3K, and Bax. 28715446 13 48 from useful 1981:1986 arg1 conclusion 1963:1972 conclusion 1963:1972 conclusion 1963:1972 In conclusion, AE is useful to prevent the exacerbation of β cell apoptosis, and it could potentially be used as adjuvant or nutraceutical therapy for diabetes. 28715446 10 49 theme caspase 1595:1601 arg1 expression 1581:1590 the expression 1577:1590 the expression of caspase 3 1577:1603 The DPP-4 inhibitor linagliptin decreased the expression of caspase 3, suggesting that DPP-4 is critically involved in apoptotic signaling. 28715446 6 50 theme rich 853:856 arg1 glucosides 871:880 rich in quercetin glucosides 853:880 rich in quercetin glucosides 853:880 Among them F1 (rich in quercetin glucosides and pentacyclic triterpene ester) and F2 (containing large amounts of carbohydrates and polysaccharides) were found to be especially effective in attenuating DPP-4 signaling, and to have the potential to counter diabetic nephropathy. 28715446 7 51 theme cells 1244:1248 arg1 apoptosis 1229:1237 the palmitate-induced apoptosis 1207:1237 the palmitate-induced apoptosis of β cells 1207:1248 Hence, the aim of the present study was to investigate whether AE subfractions can prevent the palmitate-induced apoptosis of β cells, and the putative signals involved. 28715446 13 52 theme cell 2021:2024 arg1 apoptosis 2026:2034 β cell apoptosis 2019:2034 β cell apoptosis 2019:2034 In conclusion, AE is useful to prevent the exacerbation of β cell apoptosis, and it could potentially be used as adjuvant or nutraceutical therapy for diabetes. 28715446 2 53 theme useful 337:342 arg1 tool 344:347 a useful tool 335:347 a useful tool in the treatment of T2DM 335:372 Recently dipeptidyl peptidase-4 (DPP-4) inhibitors have emerged as a useful tool in the treatment of T2DM. 28715446 3 54 theme type 390:393 arg1 GLP-1 420:424 GLP-1 420:424 GLP-1 420:424 DPP-4 degrades type 1 glucagon-like peptide (GLP-1), and GLP-1 receptor (GLP-1R) signaling has been shown to protect β cells by modulating AMPK/mTOR, PI3K, and Bax. 28715446 3 54 theme type 390:393 arg1 peptide 411:417 type 1 glucagon-like peptide 390:417 type 1 glucagon-like peptide (GLP-1) 390:425 DPP-4 degrades type 1 glucagon-like peptide (GLP-1), and GLP-1 receptor (GLP-1R) signaling has been shown to protect β cells by modulating AMPK/mTOR, PI3K, and Bax. 28715446 6 55 theme diabetic 1094:1101 arg1 nephropathy 1103:1113 diabetic nephropathy 1094:1113 diabetic nephropathy 1094:1113 Among them F1 (rich in quercetin glucosides and pentacyclic triterpene ester) and F2 (containing large amounts of carbohydrates and polysaccharides) were found to be especially effective in attenuating DPP-4 signaling, and to have the potential to counter diabetic nephropathy. 28715446 5 56 theme own 808:810 arg1 composition 812:822 its own composition 804:822 its own composition 804:822 In our recent report, a sequence of extraction steps was used to obtain a series of subfractions from AE, each with its own composition and property. 28715446 11 57 theme enzyme 1687:1692 arg1 activity 1694:1701 enzyme activity 1687:1701 enzyme activity 1687:1701 Analysis of enzyme activity revealed that palmitate increased the activity of DPP4 nearly 2 folds, while F2 especially inhibited the activation. 28715446 6 58 dep F1 849:850 arg1 ester 909:913 pentacyclic triterpene ester 886:913 pentacyclic triterpene ester 886:913 Among them F1 (rich in quercetin glucosides and pentacyclic triterpene ester) and F2 (containing large amounts of carbohydrates and polysaccharides) were found to be especially effective in attenuating DPP-4 signaling, and to have the potential to counter diabetic nephropathy. 28715446 6 58 dep F1 849:850 arg1 glucosides 871:880 rich in quercetin glucosides 853:880 rich in quercetin glucosides 853:880 Among them F1 (rich in quercetin glucosides and pentacyclic triterpene ester) and F2 (containing large amounts of carbohydrates and polysaccharides) were found to be especially effective in attenuating DPP-4 signaling, and to have the potential to counter diabetic nephropathy. 28715446 12 59 theme signaling 1940:1948 arg1 cascades 1950:1957 the palmitate-induced signaling cascades 1918:1957 the palmitate-induced signaling cascades 1918:1957 In addition, AMPK/mTOR, PI3K and mitochondrial pathways were regulated by AE, and this attenuated the palmitate-induced signaling cascades. 28715446 11 60 dep DPP4 1753:1756 arg1 folds 1767:1771 folds 1767:1771 folds 1767:1771 Analysis of enzyme activity revealed that palmitate increased the activity of DPP4 nearly 2 folds, while F2 especially inhibited the activation. 28715446 4 61 theme anti-hyperglycemic 544:561 arg1 effect 563:568 The anti-hyperglycemic effect 540:568 The anti-hyperglycemic effect of Abelmoschus esculentus (AE) 540:599 The anti-hyperglycemic effect of Abelmoschus esculentus (AE) is well known, however its mucilage makes it difficult to further examine this effect. 28715446 5 62 used used 745:748 arg2 sequence 712:719 a sequence 710:719 a sequence of extraction steps 710:739 In our recent report, a sequence of extraction steps was used to obtain a series of subfractions from AE, each with its own composition and property. 28715446 6 63 theme large 935:939 arg1 polysaccharides 970:984 polysaccharides 970:984 polysaccharides 970:984 Among them F1 (rich in quercetin glucosides and pentacyclic triterpene ester) and F2 (containing large amounts of carbohydrates and polysaccharides) were found to be especially effective in attenuating DPP-4 signaling, and to have the potential to counter diabetic nephropathy. 28715446 6 63 theme large 935:939 arg1 carbohydrates 952:964 carbohydrates 952:964 carbohydrates 952:964 Among them F1 (rich in quercetin glucosides and pentacyclic triterpene ester) and F2 (containing large amounts of carbohydrates and polysaccharides) were found to be especially effective in attenuating DPP-4 signaling, and to have the potential to counter diabetic nephropathy. 28715446 6 63 theme large 935:939 arg1 amounts 941:947 large amounts 935:947 large amounts of carbohydrates and polysaccharides 935:984 Among them F1 (rich in quercetin glucosides and pentacyclic triterpene ester) and F2 (containing large amounts of carbohydrates and polysaccharides) were found to be especially effective in attenuating DPP-4 signaling, and to have the potential to counter diabetic nephropathy. 28715446 13 64 theme nutraceutical 2085:2097 arg1 it 2041:2042 it 2041:2042 it 2041:2042 In conclusion, AE is useful to prevent the exacerbation of β cell apoptosis, and it could potentially be used as adjuvant or nutraceutical therapy for diabetes. 28715446 13 64 theme nutraceutical 2085:2097 arg1 therapy 2099:2105 adjuvant or nutraceutical therapy 2073:2105 adjuvant or nutraceutical therapy for diabetes 2073:2118 In conclusion, AE is useful to prevent the exacerbation of β cell apoptosis, and it could potentially be used as adjuvant or nutraceutical therapy for diabetes. 28715446 7 65 theme present 1138:1144 arg1 study 1146:1150 the present study 1134:1150 the present study 1134:1150 Hence, the aim of the present study was to investigate whether AE subfractions can prevent the palmitate-induced apoptosis of β cells, and the putative signals involved. 28715446 13 66 theme apoptosis 2026:2034 arg1 exacerbation 2003:2014 the exacerbation 1999:2014 the exacerbation of β cell apoptosis 1999:2034 In conclusion, AE is useful to prevent the exacerbation of β cell apoptosis, and it could potentially be used as adjuvant or nutraceutical therapy for diabetes. 28715446 0 67 theme acid-induced 79:90 arg1 apoptosis 99:107 free fatty acid-induced β cell apoptosis 68:107 free fatty acid-induced β cell apoptosis 68:107 Active subfractions of Abelmoschus esculentus substantially prevent free fatty acid-induced β cell apoptosis via inhibiting dipeptidyl peptidase-4. 28715446 8 68 theme F2 1337:1338 arg1 μg/mL 1328:1332 1 μg/mL 1326:1332 1 μg/mL of F2 1326:1338 We demonstrated that AE, and especially 1 μg/mL of F2, decreased palmitate-induced apoptosis analyzed by flow cytometry. 28715446 7 69 theme palmitate-induced 1211:1227 arg1 apoptosis 1229:1237 the palmitate-induced apoptosis 1207:1237 the palmitate-induced apoptosis of β cells 1207:1248 Hence, the aim of the present study was to investigate whether AE subfractions can prevent the palmitate-induced apoptosis of β cells, and the putative signals involved. 28715446 3 70 theme GLP-1 432:436 arg1 GLP-1R 448:453 GLP-1R 448:453 GLP-1R 448:453 DPP-4 degrades type 1 glucagon-like peptide (GLP-1), and GLP-1 receptor (GLP-1R) signaling has been shown to protect β cells by modulating AMPK/mTOR, PI3K, and Bax. 28715446 3 70 theme GLP-1 432:436 arg1 receptor 438:445 GLP-1 receptor 432:445 GLP-1 receptor (GLP-1R) signaling 432:464 DPP-4 degrades type 1 glucagon-like peptide (GLP-1), and GLP-1 receptor (GLP-1R) signaling has been shown to protect β cells by modulating AMPK/mTOR, PI3K, and Bax. 28715446 11 71 theme DPP4 1753:1756 arg1 activity 1741:1748 the activity 1737:1748 the activity of DPP4 nearly 2 folds 1737:1771 Analysis of enzyme activity revealed that palmitate increased the activity of DPP4 nearly 2 folds, while F2 especially inhibited the activation. 28715446 6 72 theme carbohydrates 952:964 arg1 polysaccharides 970:984 polysaccharides 970:984 polysaccharides 970:984 Among them F1 (rich in quercetin glucosides and pentacyclic triterpene ester) and F2 (containing large amounts of carbohydrates and polysaccharides) were found to be especially effective in attenuating DPP-4 signaling, and to have the potential to counter diabetic nephropathy. 28715446 6 72 theme carbohydrates 952:964 arg1 carbohydrates 952:964 carbohydrates 952:964 carbohydrates 952:964 Among them F1 (rich in quercetin glucosides and pentacyclic triterpene ester) and F2 (containing large amounts of carbohydrates and polysaccharides) were found to be especially effective in attenuating DPP-4 signaling, and to have the potential to counter diabetic nephropathy. 28715446 6 72 theme carbohydrates 952:964 arg1 amounts 941:947 large amounts 935:947 large amounts of carbohydrates and polysaccharides 935:984 Among them F1 (rich in quercetin glucosides and pentacyclic triterpene ester) and F2 (containing large amounts of carbohydrates and polysaccharides) were found to be especially effective in attenuating DPP-4 signaling, and to have the potential to counter diabetic nephropathy. 28715446 8 73 theme palmitate-induced 1351:1367 arg1 apoptosis 1369:1377 palmitate-induced apoptosis 1351:1377 palmitate-induced apoptosis analyzed by flow cytometry 1351:1404 We demonstrated that AE, and especially 1 μg/mL of F2, decreased palmitate-induced apoptosis analyzed by flow cytometry. 28715446 5 74 from series 762:767 arg1 each 794:797 each 794:797 each 794:797 In our recent report, a sequence of extraction steps was used to obtain a series of subfractions from AE, each with its own composition and property. 28715446 5 74 from series 762:767 arg1 AE 790:791 AE 790:791 AE 790:791 In our recent report, a sequence of extraction steps was used to obtain a series of subfractions from AE, each with its own composition and property. 28715446 1 75 theme important 170:178 arg1 role 180:183 an important role 167:183 an important role 167:183 Lipotoxicity plays an important role in exacerbating type 2 diabetes mellitus (T2DM) and leads to apoptosis of β cells. 28715446 6 76 theme triterpene 898:907 arg1 ester 909:913 pentacyclic triterpene ester 886:913 pentacyclic triterpene ester 886:913 Among them F1 (rich in quercetin glucosides and pentacyclic triterpene ester) and F2 (containing large amounts of carbohydrates and polysaccharides) were found to be especially effective in attenuating DPP-4 signaling, and to have the potential to counter diabetic nephropathy. 25848164 0 0 theme antibody 79:86 arg1 targets 88:94 the HIV-1 antibody targets 69:94 the HIV-1 antibody targets 69:94 Neutralization function affected by single amino acid replacement in the HIV-1 antibody targets. 25848164 2 1 theme Membrane 474:481 arg1 MPER 509:512 MPER 509:512 MPER 509:512 We hypothesize that the glycosylation on the HIV-1 viral envelope glycoprotein 41(gp41) at critical residues offers viral escape from the specific immune surveillant neutralizing antibodies Z13, 4E10 and 10E8 targeted to their linear epitopes in the Membrane Proximal External Region (MPER). 25848164 2 1 theme Membrane 474:481 arg1 Region 501:506 Membrane Proximal External Region 474:506 the Membrane Proximal External Region (MPER) 470:513 We hypothesize that the glycosylation on the HIV-1 viral envelope glycoprotein 41(gp41) at critical residues offers viral escape from the specific immune surveillant neutralizing antibodies Z13, 4E10 and 10E8 targeted to their linear epitopes in the Membrane Proximal External Region (MPER). 25848164 5 2 theme HIV-gp41 1028:1035 arg1 trimer 1037:1042 the 59 amino acid long HIV-gp41 trimer 1005:1042 the 59 amino acid long HIV-gp41 trimer (PDBID: 2M7W and 2LP7) 1005:1065 We analyzed the reliable frequency of glycosylation on the HIV-1 envelope gp41 using prediction tools to unravel the plausibility of the glycosylation by a mannose at 50th residue in the 59 amino acid long HIV-gp41 trimer (PDBID: 2M7W and 2LP7). 25848164 0 3 theme HIV-1 73:77 arg1 targets 88:94 the HIV-1 antibody targets 69:94 the HIV-1 antibody targets 69:94 Neutralization function affected by single amino acid replacement in the HIV-1 antibody targets. 25848164 5 4 from frequency 847:855 arg1 envelope 887:894 the HIV-1 envelope gp41 877:899 the HIV-1 envelope gp41 877:899 We analyzed the reliable frequency of glycosylation on the HIV-1 envelope gp41 using prediction tools to unravel the plausibility of the glycosylation by a mannose at 50th residue in the 59 amino acid long HIV-gp41 trimer (PDBID: 2M7W and 2LP7). 25848164 2 5 theme viral 340:344 arg1 escape 346:351 viral escape 340:351 viral escape from the specific immune surveillant neutralizing antibodies Z13, 4E10 and 10E8 targeted to their linear epitopes in the Membrane Proximal External Region (MPER) 340:513 We hypothesize that the glycosylation on the HIV-1 viral envelope glycoprotein 41(gp41) at critical residues offers viral escape from the specific immune surveillant neutralizing antibodies Z13, 4E10 and 10E8 targeted to their linear epitopes in the Membrane Proximal External Region (MPER). 25848164 6 6 theme amino-acid 1174:1183 arg1 50th 1169:1172 the 50th amino-acid 1165:1183 the 50th amino-acid 1165:1183 It is evident that the glycosylation by a mannose that masks these targets is possible only when the 50th amino-acid is N (Asparagine, Asn) which is not possible when N is mutated to D (Aspartatic acid, Asp). 25848164 6 6 theme amino-acid 1174:1183 arg1 N 1188:1188 N 1188:1188 N (Asparagine, Asn) which is not possible when N is mutated to D (Aspartatic acid, Asp) 1188:1274 It is evident that the glycosylation by a mannose that masks these targets is possible only when the 50th amino-acid is N (Asparagine, Asn) which is not possible when N is mutated to D (Aspartatic acid, Asp). 25848164 8 7 theme way 1640:1642 arg1 forward 1644:1650 a way forward 1638:1650 a way forward 1638:1650 So the glycan shields varying in their intensity and patterns have to be essentially studied to understand the viral escape strategies that will give a way forward towards a successful vaccine that can elicit a neutralizing antibody response to confer protection. 25848164 4 8 theme epitopes 710:717 arg1 rate 698:701 The glycosylation rate 680:701 The glycosylation rate of the epitopes which are shared by the Z13, 4E10 and 10E8 neutralizing antibodies of HIV-1 680:793 The glycosylation rate of the epitopes which are shared by the Z13, 4E10 and 10E8 neutralizing antibodies of HIV-1 were predicited in silico. 25848164 2 9 gly glycoprotein 290:301 arg1 glycoprotein 290:301 the HIV-1 viral envelope glycoprotein 41(gp41) 265:310 the HIV-1 viral envelope glycoprotein 41(gp41) 265:310 We hypothesize that the glycosylation on the HIV-1 viral envelope glycoprotein 41(gp41) at critical residues offers viral escape from the specific immune surveillant neutralizing antibodies Z13, 4E10 and 10E8 targeted to their linear epitopes in the Membrane Proximal External Region (MPER). 25848164 0 10 from replacement 54:64 arg1 targets 88:94 the HIV-1 antibody targets 69:94 the HIV-1 antibody targets 69:94 Neutralization function affected by single amino acid replacement in the HIV-1 antibody targets. 25848164 7 11 theme additive 1281:1288 arg1 advantage 1290:1298 The additive advantage 1277:1298 The additive advantage for the retrovirus 1277:1317 The additive advantage for the retrovirus is its error-prone reverse transcriptase which can choose to copy these survivable mutants with Asn N-50 that can be glycosylated as explained by the Copy-choice model. 25848164 7 11 theme additive 1281:1288 arg1 transcriptase 1346:1358 its error-prone reverse transcriptase 1322:1358 its error-prone reverse transcriptase which can choose to copy these survivable mutants with Asn N-50 that can be glycosylated as explained by the Copy-choice model 1322:1485 The additive advantage for the retrovirus is its error-prone reverse transcriptase which can choose to copy these survivable mutants with Asn N-50 that can be glycosylated as explained by the Copy-choice model. 25848164 2 12 theme envelope 281:288 arg1 glycoprotein 290:301 the HIV-1 viral envelope glycoprotein 41(gp41) 265:310 the HIV-1 viral envelope glycoprotein 41(gp41) 265:310 We hypothesize that the glycosylation on the HIV-1 viral envelope glycoprotein 41(gp41) at critical residues offers viral escape from the specific immune surveillant neutralizing antibodies Z13, 4E10 and 10E8 targeted to their linear epitopes in the Membrane Proximal External Region (MPER). 25848164 5 13 theme HIV-1 881:885 arg1 envelope 887:894 the HIV-1 envelope gp41 877:899 the HIV-1 envelope gp41 877:899 We analyzed the reliable frequency of glycosylation on the HIV-1 envelope gp41 using prediction tools to unravel the plausibility of the glycosylation by a mannose at 50th residue in the 59 amino acid long HIV-gp41 trimer (PDBID: 2M7W and 2LP7). 25848164 6 14 dep N 1188:1188 arg1 Asn 1203:1205 Asn 1203:1205 Asn 1203:1205 It is evident that the glycosylation by a mannose that masks these targets is possible only when the 50th amino-acid is N (Asparagine, Asn) which is not possible when N is mutated to D (Aspartatic acid, Asp). 25848164 6 14 dep N 1188:1188 arg1 Asparagine 1191:1200 Asparagine 1191:1200 Asparagine 1191:1200 It is evident that the glycosylation by a mannose that masks these targets is possible only when the 50th amino-acid is N (Asparagine, Asn) which is not possible when N is mutated to D (Aspartatic acid, Asp). 25848164 5 15 theme glycosylation 860:872 arg1 frequency 847:855 the reliable frequency 834:855 the reliable frequency of glycosylation on the HIV-1 envelope gp41 834:899 We analyzed the reliable frequency of glycosylation on the HIV-1 envelope gp41 using prediction tools to unravel the plausibility of the glycosylation by a mannose at 50th residue in the 59 amino acid long HIV-gp41 trimer (PDBID: 2M7W and 2LP7). 25848164 2 16 from residues 324:331 arg1 glycosylation 248:260 the glycosylation 244:260 the glycosylation on the HIV-1 viral envelope glycoprotein 41(gp41) at critical residues 244:331 We hypothesize that the glycosylation on the HIV-1 viral envelope glycoprotein 41(gp41) at critical residues offers viral escape from the specific immune surveillant neutralizing antibodies Z13, 4E10 and 10E8 targeted to their linear epitopes in the Membrane Proximal External Region (MPER). 25848164 2 17 theme viral 275:279 arg1 glycoprotein 290:301 the HIV-1 viral envelope glycoprotein 41(gp41) 265:310 the HIV-1 viral envelope glycoprotein 41(gp41) 265:310 We hypothesize that the glycosylation on the HIV-1 viral envelope glycoprotein 41(gp41) at critical residues offers viral escape from the specific immune surveillant neutralizing antibodies Z13, 4E10 and 10E8 targeted to their linear epitopes in the Membrane Proximal External Region (MPER). 25848164 1 18 theme host 165:168 arg1 cells 170:174 their host cells 159:174 their host cells 159:174 The viral envelope glycoproteins are essential for entry into their host cells and studied extensively for designing vaccines. 25848164 6 19 theme Aspartatic 1254:1263 arg1 Asp 1271:1273 Asp 1271:1273 Asp 1271:1273 It is evident that the glycosylation by a mannose that masks these targets is possible only when the 50th amino-acid is N (Asparagine, Asn) which is not possible when N is mutated to D (Aspartatic acid, Asp). 25848164 6 19 theme Aspartatic 1254:1263 arg1 acid 1265:1268 Aspartatic acid 1254:1268 Aspartatic acid 1254:1268 It is evident that the glycosylation by a mannose that masks these targets is possible only when the 50th amino-acid is N (Asparagine, Asn) which is not possible when N is mutated to D (Aspartatic acid, Asp). 25848164 7 20 theme reverse 1338:1344 arg1 transcriptase 1346:1358 its error-prone reverse transcriptase 1322:1358 its error-prone reverse transcriptase which can choose to copy these survivable mutants with Asn N-50 that can be glycosylated as explained by the Copy-choice model 1322:1485 The additive advantage for the retrovirus is its error-prone reverse transcriptase which can choose to copy these survivable mutants with Asn N-50 that can be glycosylated as explained by the Copy-choice model. 25848164 7 20 theme reverse 1338:1344 arg1 advantage 1290:1298 The additive advantage 1277:1298 The additive advantage for the retrovirus 1277:1317 The additive advantage for the retrovirus is its error-prone reverse transcriptase which can choose to copy these survivable mutants with Asn N-50 that can be glycosylated as explained by the Copy-choice model. 25848164 4 21 theme HIV-1 789:793 arg1 4E10 748:751 4E10 748:751 4E10 748:751 The glycosylation rate of the epitopes which are shared by the Z13, 4E10 and 10E8 neutralizing antibodies of HIV-1 were predicited in silico. 25848164 4 21 theme HIV-1 789:793 arg1 Z13 743:745 Z13 743:745 Z13 743:745 The glycosylation rate of the epitopes which are shared by the Z13, 4E10 and 10E8 neutralizing antibodies of HIV-1 were predicited in silico. 25848164 4 21 theme HIV-1 789:793 arg1 antibodies 775:784 10E8 neutralizing antibodies 757:784 10E8 neutralizing antibodies 757:784 The glycosylation rate of the epitopes which are shared by the Z13, 4E10 and 10E8 neutralizing antibodies of HIV-1 were predicited in silico. 25848164 7 22 gly glycosylated 1436:1447 arg1 Asn 1415:1417 Asn N-50 1415:1422 Asn N-50 that can be glycosylated as explained by the Copy-choice model 1415:1485 The additive advantage for the retrovirus is its error-prone reverse transcriptase which can choose to copy these survivable mutants with Asn N-50 that can be glycosylated as explained by the Copy-choice model. 25848164 2 23 theme HIV-1 269:273 arg1 glycoprotein 290:301 the HIV-1 viral envelope glycoprotein 41(gp41) 265:310 the HIV-1 viral envelope glycoprotein 41(gp41) 265:310 We hypothesize that the glycosylation on the HIV-1 viral envelope glycoprotein 41(gp41) at critical residues offers viral escape from the specific immune surveillant neutralizing antibodies Z13, 4E10 and 10E8 targeted to their linear epitopes in the Membrane Proximal External Region (MPER). 25848164 2 24 theme surveillant 378:388 arg1 Z13 414:416 Z13 414:416 Z13 414:416 We hypothesize that the glycosylation on the HIV-1 viral envelope glycoprotein 41(gp41) at critical residues offers viral escape from the specific immune surveillant neutralizing antibodies Z13, 4E10 and 10E8 targeted to their linear epitopes in the Membrane Proximal External Region (MPER). 25848164 2 24 theme surveillant 378:388 arg1 10E8 428:431 10E8 428:431 10E8 428:431 We hypothesize that the glycosylation on the HIV-1 viral envelope glycoprotein 41(gp41) at critical residues offers viral escape from the specific immune surveillant neutralizing antibodies Z13, 4E10 and 10E8 targeted to their linear epitopes in the Membrane Proximal External Region (MPER). 25848164 2 24 theme surveillant 378:388 arg1 antibodies 403:412 the specific immune surveillant neutralizing antibodies 358:412 the specific immune surveillant neutralizing antibodies Z13, 4E10 and 10E8 targeted to their linear epitopes in the Membrane Proximal External Region (MPER) 358:513 We hypothesize that the glycosylation on the HIV-1 viral envelope glycoprotein 41(gp41) at critical residues offers viral escape from the specific immune surveillant neutralizing antibodies Z13, 4E10 and 10E8 targeted to their linear epitopes in the Membrane Proximal External Region (MPER). 25848164 2 24 theme surveillant 378:388 arg1 4E10 419:422 4E10 419:422 4E10 419:422 We hypothesize that the glycosylation on the HIV-1 viral envelope glycoprotein 41(gp41) at critical residues offers viral escape from the specific immune surveillant neutralizing antibodies Z13, 4E10 and 10E8 targeted to their linear epitopes in the Membrane Proximal External Region (MPER). 25848164 2 25 from epitopes 458:465 arg1 MPER 509:512 MPER 509:512 MPER 509:512 We hypothesize that the glycosylation on the HIV-1 viral envelope glycoprotein 41(gp41) at critical residues offers viral escape from the specific immune surveillant neutralizing antibodies Z13, 4E10 and 10E8 targeted to their linear epitopes in the Membrane Proximal External Region (MPER). 25848164 2 25 from epitopes 458:465 arg1 Region 501:506 Membrane Proximal External Region 474:506 the Membrane Proximal External Region (MPER) 470:513 We hypothesize that the glycosylation on the HIV-1 viral envelope glycoprotein 41(gp41) at critical residues offers viral escape from the specific immune surveillant neutralizing antibodies Z13, 4E10 and 10E8 targeted to their linear epitopes in the Membrane Proximal External Region (MPER). 25848164 8 26 theme successful 1662:1671 arg1 vaccine 1673:1679 a successful vaccine 1660:1679 a successful vaccine that can elicit a neutralizing antibody response to confer protection 1660:1749 So the glycan shields varying in their intensity and patterns have to be essentially studied to understand the viral escape strategies that will give a way forward towards a successful vaccine that can elicit a neutralizing antibody response to confer protection. 25848164 3 27 theme 50th 551:554 arg1 Asparagine 565:574 Asparagine 565:574 Asparagine 565:574 The glycosylation occurring on the 50th residue (Asparagine) contained in the target (NWFNIT) can mask itself to be inaccessible for these neutralizing antibodies. 25848164 3 27 theme 50th 551:554 arg1 residue 556:562 the 50th residue 547:562 the 50th residue (Asparagine) contained in the target (NWFNIT) 547:608 The glycosylation occurring on the 50th residue (Asparagine) contained in the target (NWFNIT) can mask itself to be inaccessible for these neutralizing antibodies. 25848164 2 28 theme immune 371:376 arg1 Z13 414:416 Z13 414:416 Z13 414:416 We hypothesize that the glycosylation on the HIV-1 viral envelope glycoprotein 41(gp41) at critical residues offers viral escape from the specific immune surveillant neutralizing antibodies Z13, 4E10 and 10E8 targeted to their linear epitopes in the Membrane Proximal External Region (MPER). 25848164 2 28 theme immune 371:376 arg1 10E8 428:431 10E8 428:431 10E8 428:431 We hypothesize that the glycosylation on the HIV-1 viral envelope glycoprotein 41(gp41) at critical residues offers viral escape from the specific immune surveillant neutralizing antibodies Z13, 4E10 and 10E8 targeted to their linear epitopes in the Membrane Proximal External Region (MPER). 25848164 2 28 theme immune 371:376 arg1 antibodies 403:412 the specific immune surveillant neutralizing antibodies 358:412 the specific immune surveillant neutralizing antibodies Z13, 4E10 and 10E8 targeted to their linear epitopes in the Membrane Proximal External Region (MPER) 358:513 We hypothesize that the glycosylation on the HIV-1 viral envelope glycoprotein 41(gp41) at critical residues offers viral escape from the specific immune surveillant neutralizing antibodies Z13, 4E10 and 10E8 targeted to their linear epitopes in the Membrane Proximal External Region (MPER). 25848164 2 28 theme immune 371:376 arg1 4E10 419:422 4E10 419:422 4E10 419:422 We hypothesize that the glycosylation on the HIV-1 viral envelope glycoprotein 41(gp41) at critical residues offers viral escape from the specific immune surveillant neutralizing antibodies Z13, 4E10 and 10E8 targeted to their linear epitopes in the Membrane Proximal External Region (MPER). 25848164 0 29 theme Neutralization 0:13 arg1 function 15:22 Neutralization function 0:22 Neutralization function 0:22 Neutralization function affected by single amino acid replacement in the HIV-1 antibody targets. 25848164 6 30 dep D 1251:1251 arg1 Asp 1271:1273 Asp 1271:1273 Asp 1271:1273 It is evident that the glycosylation by a mannose that masks these targets is possible only when the 50th amino-acid is N (Asparagine, Asn) which is not possible when N is mutated to D (Aspartatic acid, Asp). 25848164 6 30 dep D 1251:1251 arg1 acid 1265:1268 Aspartatic acid 1254:1268 Aspartatic acid 1254:1268 It is evident that the glycosylation by a mannose that masks these targets is possible only when the 50th amino-acid is N (Asparagine, Asn) which is not possible when N is mutated to D (Aspartatic acid, Asp). 25848164 5 31 from glycosylation 860:872 arg1 envelope 887:894 the HIV-1 envelope gp41 877:899 the HIV-1 envelope gp41 877:899 We analyzed the reliable frequency of glycosylation on the HIV-1 envelope gp41 using prediction tools to unravel the plausibility of the glycosylation by a mannose at 50th residue in the 59 amino acid long HIV-gp41 trimer (PDBID: 2M7W and 2LP7). 25848164 2 32 from glycosylation 248:260 arg1 glycoprotein 290:301 the HIV-1 viral envelope glycoprotein 41(gp41) 265:310 the HIV-1 viral envelope glycoprotein 41(gp41) 265:310 We hypothesize that the glycosylation on the HIV-1 viral envelope glycoprotein 41(gp41) at critical residues offers viral escape from the specific immune surveillant neutralizing antibodies Z13, 4E10 and 10E8 targeted to their linear epitopes in the Membrane Proximal External Region (MPER). 25848164 2 33 theme specific 362:369 arg1 Z13 414:416 Z13 414:416 Z13 414:416 We hypothesize that the glycosylation on the HIV-1 viral envelope glycoprotein 41(gp41) at critical residues offers viral escape from the specific immune surveillant neutralizing antibodies Z13, 4E10 and 10E8 targeted to their linear epitopes in the Membrane Proximal External Region (MPER). 25848164 2 33 theme specific 362:369 arg1 10E8 428:431 10E8 428:431 10E8 428:431 We hypothesize that the glycosylation on the HIV-1 viral envelope glycoprotein 41(gp41) at critical residues offers viral escape from the specific immune surveillant neutralizing antibodies Z13, 4E10 and 10E8 targeted to their linear epitopes in the Membrane Proximal External Region (MPER). 25848164 2 33 theme specific 362:369 arg1 antibodies 403:412 the specific immune surveillant neutralizing antibodies 358:412 the specific immune surveillant neutralizing antibodies Z13, 4E10 and 10E8 targeted to their linear epitopes in the Membrane Proximal External Region (MPER) 358:513 We hypothesize that the glycosylation on the HIV-1 viral envelope glycoprotein 41(gp41) at critical residues offers viral escape from the specific immune surveillant neutralizing antibodies Z13, 4E10 and 10E8 targeted to their linear epitopes in the Membrane Proximal External Region (MPER). 25848164 2 33 theme specific 362:369 arg1 4E10 419:422 4E10 419:422 4E10 419:422 We hypothesize that the glycosylation on the HIV-1 viral envelope glycoprotein 41(gp41) at critical residues offers viral escape from the specific immune surveillant neutralizing antibodies Z13, 4E10 and 10E8 targeted to their linear epitopes in the Membrane Proximal External Region (MPER). 25848164 1 34 gly glycoproteins 116:128 arg1 essential 134:142 essential 134:142 essential 134:142 The viral envelope glycoproteins are essential for entry into their host cells and studied extensively for designing vaccines. 25848164 1 34 gly glycoproteins 116:128 arg1 glycoproteins 116:128 The viral envelope glycoproteins 97:128 The viral envelope glycoproteins 97:128 The viral envelope glycoproteins are essential for entry into their host cells and studied extensively for designing vaccines. 25848164 5 35 from residue 994:1000 arg1 mannose 978:984 a mannose 976:984 a mannose at 50th residue in the 59 amino acid long HIV-gp41 trimer (PDBID: 2M7W and 2LP7) 976:1065 We analyzed the reliable frequency of glycosylation on the HIV-1 envelope gp41 using prediction tools to unravel the plausibility of the glycosylation by a mannose at 50th residue in the 59 amino acid long HIV-gp41 trimer (PDBID: 2M7W and 2LP7). 25848164 5 35 from residue 994:1000 arg1 trimer 1037:1042 the 59 amino acid long HIV-gp41 trimer 1005:1042 the 59 amino acid long HIV-gp41 trimer (PDBID: 2M7W and 2LP7) 1005:1065 We analyzed the reliable frequency of glycosylation on the HIV-1 envelope gp41 using prediction tools to unravel the plausibility of the glycosylation by a mannose at 50th residue in the 59 amino acid long HIV-gp41 trimer (PDBID: 2M7W and 2LP7). 25848164 7 36 with copy 1380:1383 arg1 Asn 1415:1417 Asn N-50 1415:1422 Asn N-50 that can be glycosylated as explained by the Copy-choice model 1415:1485 The additive advantage for the retrovirus is its error-prone reverse transcriptase which can choose to copy these survivable mutants with Asn N-50 that can be glycosylated as explained by the Copy-choice model. 25848164 2 37 gly glycosylation 248:260 arg1 residues 324:331 critical residues 315:331 critical residues 315:331 We hypothesize that the glycosylation on the HIV-1 viral envelope glycoprotein 41(gp41) at critical residues offers viral escape from the specific immune surveillant neutralizing antibodies Z13, 4E10 and 10E8 targeted to their linear epitopes in the Membrane Proximal External Region (MPER). 25848164 2 37 gly glycosylation 248:260 arg1 glycoprotein 290:301 the HIV-1 viral envelope glycoprotein 41(gp41) 265:310 the HIV-1 viral envelope glycoprotein 41(gp41) 265:310 We hypothesize that the glycosylation on the HIV-1 viral envelope glycoprotein 41(gp41) at critical residues offers viral escape from the specific immune surveillant neutralizing antibodies Z13, 4E10 and 10E8 targeted to their linear epitopes in the Membrane Proximal External Region (MPER). 25848164 2 37 gly glycosylation 248:260 arg2 residues 324:331 critical residues 315:331 critical residues 315:331 We hypothesize that the glycosylation on the HIV-1 viral envelope glycoprotein 41(gp41) at critical residues offers viral escape from the specific immune surveillant neutralizing antibodies Z13, 4E10 and 10E8 targeted to their linear epitopes in the Membrane Proximal External Region (MPER). 25848164 7 38 theme Copy-choice 1469:1479 arg1 model 1481:1485 the Copy-choice model 1465:1485 the Copy-choice model 1465:1485 The additive advantage for the retrovirus is its error-prone reverse transcriptase which can choose to copy these survivable mutants with Asn N-50 that can be glycosylated as explained by the Copy-choice model. 25848164 5 39 gly glycosylation 860:872 arg1 envelope 887:894 the HIV-1 envelope gp41 877:899 the HIV-1 envelope gp41 877:899 We analyzed the reliable frequency of glycosylation on the HIV-1 envelope gp41 using prediction tools to unravel the plausibility of the glycosylation by a mannose at 50th residue in the 59 amino acid long HIV-gp41 trimer (PDBID: 2M7W and 2LP7). 25848164 1 40 theme viral 101:105 arg1 essential 134:142 essential 134:142 essential 134:142 The viral envelope glycoproteins are essential for entry into their host cells and studied extensively for designing vaccines. 25848164 1 40 theme viral 101:105 arg1 glycoproteins 116:128 The viral envelope glycoproteins 97:128 The viral envelope glycoproteins 97:128 The viral envelope glycoproteins are essential for entry into their host cells and studied extensively for designing vaccines. 25848164 0 41 theme amino 43:47 arg1 replacement 54:64 single amino acid replacement 36:64 single amino acid replacement in the HIV-1 antibody targets 36:94 Neutralization function affected by single amino acid replacement in the HIV-1 antibody targets. 25848164 8 42 theme neutralizing 1699:1710 arg1 response 1721:1728 a neutralizing antibody response 1697:1728 a neutralizing antibody response 1697:1728 So the glycan shields varying in their intensity and patterns have to be essentially studied to understand the viral escape strategies that will give a way forward towards a successful vaccine that can elicit a neutralizing antibody response to confer protection. 25848164 5 43 theme amino 1012:1016 arg1 trimer 1037:1042 the 59 amino acid long HIV-gp41 trimer 1005:1042 the 59 amino acid long HIV-gp41 trimer (PDBID: 2M7W and 2LP7) 1005:1065 We analyzed the reliable frequency of glycosylation on the HIV-1 envelope gp41 using prediction tools to unravel the plausibility of the glycosylation by a mannose at 50th residue in the 59 amino acid long HIV-gp41 trimer (PDBID: 2M7W and 2LP7). 25848164 4 44 theme neutralizing 762:773 arg1 antibodies 775:784 10E8 neutralizing antibodies 757:784 10E8 neutralizing antibodies 757:784 The glycosylation rate of the epitopes which are shared by the Z13, 4E10 and 10E8 neutralizing antibodies of HIV-1 were predicited in silico. 25848164 4 45 dep Z13 743:745 arg1 the 739:741 the 739:741 the 739:741 The glycosylation rate of the epitopes which are shared by the Z13, 4E10 and 10E8 neutralizing antibodies of HIV-1 were predicited in silico. 25848164 0 46 theme single 36:41 arg1 replacement 54:64 single amino acid replacement 36:64 single amino acid replacement in the HIV-1 antibody targets 36:94 Neutralization function affected by single amino acid replacement in the HIV-1 antibody targets. 25848164 5 47 theme acid 1018:1021 arg1 trimer 1037:1042 the 59 amino acid long HIV-gp41 trimer 1005:1042 the 59 amino acid long HIV-gp41 trimer (PDBID: 2M7W and 2LP7) 1005:1065 We analyzed the reliable frequency of glycosylation on the HIV-1 envelope gp41 using prediction tools to unravel the plausibility of the glycosylation by a mannose at 50th residue in the 59 amino acid long HIV-gp41 trimer (PDBID: 2M7W and 2LP7). 25848164 2 48 dep antibodies 403:412 arg1 Z13 414:416 Z13 414:416 Z13 414:416 We hypothesize that the glycosylation on the HIV-1 viral envelope glycoprotein 41(gp41) at critical residues offers viral escape from the specific immune surveillant neutralizing antibodies Z13, 4E10 and 10E8 targeted to their linear epitopes in the Membrane Proximal External Region (MPER). 25848164 2 48 dep antibodies 403:412 arg1 10E8 428:431 10E8 428:431 10E8 428:431 We hypothesize that the glycosylation on the HIV-1 viral envelope glycoprotein 41(gp41) at critical residues offers viral escape from the specific immune surveillant neutralizing antibodies Z13, 4E10 and 10E8 targeted to their linear epitopes in the Membrane Proximal External Region (MPER). 25848164 2 48 dep antibodies 403:412 arg1 antibodies 403:412 the specific immune surveillant neutralizing antibodies 358:412 the specific immune surveillant neutralizing antibodies Z13, 4E10 and 10E8 targeted to their linear epitopes in the Membrane Proximal External Region (MPER) 358:513 We hypothesize that the glycosylation on the HIV-1 viral envelope glycoprotein 41(gp41) at critical residues offers viral escape from the specific immune surveillant neutralizing antibodies Z13, 4E10 and 10E8 targeted to their linear epitopes in the Membrane Proximal External Region (MPER). 25848164 2 48 dep antibodies 403:412 arg1 4E10 419:422 4E10 419:422 4E10 419:422 We hypothesize that the glycosylation on the HIV-1 viral envelope glycoprotein 41(gp41) at critical residues offers viral escape from the specific immune surveillant neutralizing antibodies Z13, 4E10 and 10E8 targeted to their linear epitopes in the Membrane Proximal External Region (MPER). 25848164 8 49 theme viral 1599:1603 arg1 strategies 1612:1621 the viral escape strategies 1595:1621 the viral escape strategies that will give a way forward towards a successful vaccine that can elicit a neutralizing antibody response to confer protection 1595:1749 So the glycan shields varying in their intensity and patterns have to be essentially studied to understand the viral escape strategies that will give a way forward towards a successful vaccine that can elicit a neutralizing antibody response to confer protection. 25848164 8 50 theme glycan 1495:1500 arg1 shields 1502:1508 So the glycan shields 1488:1508 So the glycan shields 1488:1508 So the glycan shields varying in their intensity and patterns have to be essentially studied to understand the viral escape strategies that will give a way forward towards a successful vaccine that can elicit a neutralizing antibody response to confer protection. 25848164 2 51 theme linear 451:456 arg1 epitopes 458:465 their linear epitopes 445:465 their linear epitopes in the Membrane Proximal External Region (MPER) 445:513 We hypothesize that the glycosylation on the HIV-1 viral envelope glycoprotein 41(gp41) at critical residues offers viral escape from the specific immune surveillant neutralizing antibodies Z13, 4E10 and 10E8 targeted to their linear epitopes in the Membrane Proximal External Region (MPER). 25848164 5 52 dep PDBID 1045:1049 arg1 2M7W 1052:1055 2M7W 1052:1055 2M7W 1052:1055 We analyzed the reliable frequency of glycosylation on the HIV-1 envelope gp41 using prediction tools to unravel the plausibility of the glycosylation by a mannose at 50th residue in the 59 amino acid long HIV-gp41 trimer (PDBID: 2M7W and 2LP7). 25848164 5 52 dep PDBID 1045:1049 arg1 2LP7 1061:1064 2LP7 1061:1064 2LP7 1061:1064 We analyzed the reliable frequency of glycosylation on the HIV-1 envelope gp41 using prediction tools to unravel the plausibility of the glycosylation by a mannose at 50th residue in the 59 amino acid long HIV-gp41 trimer (PDBID: 2M7W and 2LP7). 25848164 5 53 theme long 1023:1026 arg1 trimer 1037:1042 the 59 amino acid long HIV-gp41 trimer 1005:1042 the 59 amino acid long HIV-gp41 trimer (PDBID: 2M7W and 2LP7) 1005:1065 We analyzed the reliable frequency of glycosylation on the HIV-1 envelope gp41 using prediction tools to unravel the plausibility of the glycosylation by a mannose at 50th residue in the 59 amino acid long HIV-gp41 trimer (PDBID: 2M7W and 2LP7). 25848164 1 54 theme envelope 107:114 arg1 essential 134:142 essential 134:142 essential 134:142 The viral envelope glycoproteins are essential for entry into their host cells and studied extensively for designing vaccines. 25848164 1 54 theme envelope 107:114 arg1 glycoproteins 116:128 The viral envelope glycoproteins 97:128 The viral envelope glycoproteins 97:128 The viral envelope glycoproteins are essential for entry into their host cells and studied extensively for designing vaccines. 25848164 0 55 theme acid 49:52 arg1 replacement 54:64 single amino acid replacement 36:64 single amino acid replacement in the HIV-1 antibody targets 36:94 Neutralization function affected by single amino acid replacement in the HIV-1 antibody targets. 25848164 2 56 theme neutralizing 390:401 arg1 Z13 414:416 Z13 414:416 Z13 414:416 We hypothesize that the glycosylation on the HIV-1 viral envelope glycoprotein 41(gp41) at critical residues offers viral escape from the specific immune surveillant neutralizing antibodies Z13, 4E10 and 10E8 targeted to their linear epitopes in the Membrane Proximal External Region (MPER). 25848164 2 56 theme neutralizing 390:401 arg1 10E8 428:431 10E8 428:431 10E8 428:431 We hypothesize that the glycosylation on the HIV-1 viral envelope glycoprotein 41(gp41) at critical residues offers viral escape from the specific immune surveillant neutralizing antibodies Z13, 4E10 and 10E8 targeted to their linear epitopes in the Membrane Proximal External Region (MPER). 25848164 2 56 theme neutralizing 390:401 arg1 antibodies 403:412 the specific immune surveillant neutralizing antibodies 358:412 the specific immune surveillant neutralizing antibodies Z13, 4E10 and 10E8 targeted to their linear epitopes in the Membrane Proximal External Region (MPER) 358:513 We hypothesize that the glycosylation on the HIV-1 viral envelope glycoprotein 41(gp41) at critical residues offers viral escape from the specific immune surveillant neutralizing antibodies Z13, 4E10 and 10E8 targeted to their linear epitopes in the Membrane Proximal External Region (MPER). 25848164 2 56 theme neutralizing 390:401 arg1 4E10 419:422 4E10 419:422 4E10 419:422 We hypothesize that the glycosylation on the HIV-1 viral envelope glycoprotein 41(gp41) at critical residues offers viral escape from the specific immune surveillant neutralizing antibodies Z13, 4E10 and 10E8 targeted to their linear epitopes in the Membrane Proximal External Region (MPER). 25848164 7 57 theme error-prone 1326:1336 arg1 transcriptase 1346:1358 its error-prone reverse transcriptase 1322:1358 its error-prone reverse transcriptase which can choose to copy these survivable mutants with Asn N-50 that can be glycosylated as explained by the Copy-choice model 1322:1485 The additive advantage for the retrovirus is its error-prone reverse transcriptase which can choose to copy these survivable mutants with Asn N-50 that can be glycosylated as explained by the Copy-choice model. 25848164 7 57 theme error-prone 1326:1336 arg1 advantage 1290:1298 The additive advantage 1277:1298 The additive advantage for the retrovirus 1277:1317 The additive advantage for the retrovirus is its error-prone reverse transcriptase which can choose to copy these survivable mutants with Asn N-50 that can be glycosylated as explained by the Copy-choice model. 25848164 5 58 theme 50th 989:992 arg1 residue 994:1000 50th residue 989:1000 50th residue in the 59 amino acid long HIV-gp41 trimer (PDBID: 2M7W and 2LP7) 989:1065 We analyzed the reliable frequency of glycosylation on the HIV-1 envelope gp41 using prediction tools to unravel the plausibility of the glycosylation by a mannose at 50th residue in the 59 amino acid long HIV-gp41 trimer (PDBID: 2M7W and 2LP7). 25848164 8 59 theme antibody 1712:1719 arg1 response 1721:1728 a neutralizing antibody response 1697:1728 a neutralizing antibody response 1697:1728 So the glycan shields varying in their intensity and patterns have to be essentially studied to understand the viral escape strategies that will give a way forward towards a successful vaccine that can elicit a neutralizing antibody response to confer protection. 25848164 7 60 theme survivable 1391:1400 arg1 mutants 1402:1408 these survivable mutants 1385:1408 these survivable mutants 1385:1408 The additive advantage for the retrovirus is its error-prone reverse transcriptase which can choose to copy these survivable mutants with Asn N-50 that can be glycosylated as explained by the Copy-choice model. 25848164 5 61 dep trimer 1037:1042 arg1 PDBID 1045:1049 PDBID 1045:1049 PDBID: 2M7W and 2LP7 1045:1064 We analyzed the reliable frequency of glycosylation on the HIV-1 envelope gp41 using prediction tools to unravel the plausibility of the glycosylation by a mannose at 50th residue in the 59 amino acid long HIV-gp41 trimer (PDBID: 2M7W and 2LP7). 25848164 4 62 theme 10E8 757:760 arg1 antibodies 775:784 10E8 neutralizing antibodies 757:784 10E8 neutralizing antibodies 757:784 The glycosylation rate of the epitopes which are shared by the Z13, 4E10 and 10E8 neutralizing antibodies of HIV-1 were predicited in silico. 25848164 2 63 theme critical 315:322 arg1 residues 324:331 critical residues 315:331 critical residues 315:331 We hypothesize that the glycosylation on the HIV-1 viral envelope glycoprotein 41(gp41) at critical residues offers viral escape from the specific immune surveillant neutralizing antibodies Z13, 4E10 and 10E8 targeted to their linear epitopes in the Membrane Proximal External Region (MPER). 25848164 8 64 theme escape 1605:1610 arg1 strategies 1612:1621 the viral escape strategies 1595:1621 the viral escape strategies that will give a way forward towards a successful vaccine that can elicit a neutralizing antibody response to confer protection 1595:1749 So the glycan shields varying in their intensity and patterns have to be essentially studied to understand the viral escape strategies that will give a way forward towards a successful vaccine that can elicit a neutralizing antibody response to confer protection. 25848164 4 65 theme glycosylation 684:696 arg1 rate 698:701 The glycosylation rate 680:701 The glycosylation rate of the epitopes which are shared by the Z13, 4E10 and 10E8 neutralizing antibodies of HIV-1 680:793 The glycosylation rate of the epitopes which are shared by the Z13, 4E10 and 10E8 neutralizing antibodies of HIV-1 were predicited in silico. 25848164 5 66 from envelope 887:894 arg1 frequency 847:855 the reliable frequency 834:855 the reliable frequency of glycosylation on the HIV-1 envelope gp41 834:899 We analyzed the reliable frequency of glycosylation on the HIV-1 envelope gp41 using prediction tools to unravel the plausibility of the glycosylation by a mannose at 50th residue in the 59 amino acid long HIV-gp41 trimer (PDBID: 2M7W and 2LP7). 25848164 2 67 theme External 492:499 arg1 MPER 509:512 MPER 509:512 MPER 509:512 We hypothesize that the glycosylation on the HIV-1 viral envelope glycoprotein 41(gp41) at critical residues offers viral escape from the specific immune surveillant neutralizing antibodies Z13, 4E10 and 10E8 targeted to their linear epitopes in the Membrane Proximal External Region (MPER). 25848164 2 67 theme External 492:499 arg1 Region 501:506 Membrane Proximal External Region 474:506 the Membrane Proximal External Region (MPER) 470:513 We hypothesize that the glycosylation on the HIV-1 viral envelope glycoprotein 41(gp41) at critical residues offers viral escape from the specific immune surveillant neutralizing antibodies Z13, 4E10 and 10E8 targeted to their linear epitopes in the Membrane Proximal External Region (MPER). 25848164 2 68 from antibodies 403:412 arg1 escape 346:351 viral escape 340:351 viral escape from the specific immune surveillant neutralizing antibodies Z13, 4E10 and 10E8 targeted to their linear epitopes in the Membrane Proximal External Region (MPER) 340:513 We hypothesize that the glycosylation on the HIV-1 viral envelope glycoprotein 41(gp41) at critical residues offers viral escape from the specific immune surveillant neutralizing antibodies Z13, 4E10 and 10E8 targeted to their linear epitopes in the Membrane Proximal External Region (MPER). 25848164 5 69 theme prediction 907:916 arg1 tools 918:922 prediction tools 907:922 prediction tools 907:922 We analyzed the reliable frequency of glycosylation on the HIV-1 envelope gp41 using prediction tools to unravel the plausibility of the glycosylation by a mannose at 50th residue in the 59 amino acid long HIV-gp41 trimer (PDBID: 2M7W and 2LP7). 25848164 2 70 theme Proximal 483:490 arg1 MPER 509:512 MPER 509:512 MPER 509:512 We hypothesize that the glycosylation on the HIV-1 viral envelope glycoprotein 41(gp41) at critical residues offers viral escape from the specific immune surveillant neutralizing antibodies Z13, 4E10 and 10E8 targeted to their linear epitopes in the Membrane Proximal External Region (MPER). 25848164 2 70 theme Proximal 483:490 arg1 Region 501:506 Membrane Proximal External Region 474:506 the Membrane Proximal External Region (MPER) 470:513 We hypothesize that the glycosylation on the HIV-1 viral envelope glycoprotein 41(gp41) at critical residues offers viral escape from the specific immune surveillant neutralizing antibodies Z13, 4E10 and 10E8 targeted to their linear epitopes in the Membrane Proximal External Region (MPER). 25848164 3 71 theme neutralizing 655:666 arg1 antibodies 668:677 these neutralizing antibodies 649:677 these neutralizing antibodies 649:677 The glycosylation occurring on the 50th residue (Asparagine) contained in the target (NWFNIT) can mask itself to be inaccessible for these neutralizing antibodies. 25848164 5 72 theme glycosylation 959:971 arg1 plausibility 939:950 the plausibility 935:950 the plausibility of the glycosylation by a mannose at 50th residue in the 59 amino acid long HIV-gp41 trimer (PDBID: 2M7W and 2LP7) 935:1065 We analyzed the reliable frequency of glycosylation on the HIV-1 envelope gp41 using prediction tools to unravel the plausibility of the glycosylation by a mannose at 50th residue in the 59 amino acid long HIV-gp41 trimer (PDBID: 2M7W and 2LP7). 25848164 5 73 theme reliable 838:845 arg1 frequency 847:855 the reliable frequency 834:855 the reliable frequency of glycosylation on the HIV-1 envelope gp41 834:899 We analyzed the reliable frequency of glycosylation on the HIV-1 envelope gp41 using prediction tools to unravel the plausibility of the glycosylation by a mannose at 50th residue in the 59 amino acid long HIV-gp41 trimer (PDBID: 2M7W and 2LP7). 28595377 1 0 link O-linked 76:83 arg1 β-N-acetylglucosamine 85:105 O-linked β-N-acetylglucosamine 76:105 O-linked β-N-acetylglucosamine (O-GlcNAc) 76:116 O-linked β-N-acetylglucosamine (O-GlcNAc) is an essential regulatory post-translational modification of thousands of nuclear, cytoplasmic, and mitochondrial proteins. 28595377 1 0 link O-linked 76:83 arg1 modification 164:175 an essential regulatory post-translational modification 121:175 an essential regulatory post-translational modification of thousands of nuclear, cytoplasmic, and mitochondrial proteins 121:240 O-linked β-N-acetylglucosamine (O-GlcNAc) is an essential regulatory post-translational modification of thousands of nuclear, cytoplasmic, and mitochondrial proteins. 28595377 1 0 link O-linked 76:83 arg1 O-GlcNAc 108:115 O-GlcNAc 108:115 O-GlcNAc 108:115 O-linked β-N-acetylglucosamine (O-GlcNAc) is an essential regulatory post-translational modification of thousands of nuclear, cytoplasmic, and mitochondrial proteins. 28595377 5 1 theme Abcam 777:781 arg1 Laboratories 794:805 Abcam and Bethyl Laboratories 777:805 Abcam and Bethyl Laboratories 777:805 Here, we report that antibodies from Abcam and Bethyl Laboratories can be used to immunoprecipitate OGA to near-saturation from human and mouse cell lysates. 28595377 6 2 theme full-length 1044:1054 arg1 OGA 1056:1058 full-length OGA 1044:1058 full-length OGA 1044:1058 However, Western blotting analysis indicates that both antibodies, as well as three non-commercially available antibodies (345, 346, 352), detect full-length OGA and numerous cross-reacting proteins. 28595377 4 3 theme mouse 716:720 arg1 lysates 705:711 lysates 705:711 lysates of mouse and human origin 705:737 To facilitate studies focused on the role of O-GlcNAc and OGA in disease, we sought to identify commercially available antibodies that enable the enrichment of full-length OGA from lysates of mouse and human origin. 28595377 5 4 from Laboratories 794:805 arg1 antibodies 761:770 antibodies 761:770 antibodies from Abcam and Bethyl Laboratories 761:805 Here, we report that antibodies from Abcam and Bethyl Laboratories can be used to immunoprecipitate OGA to near-saturation from human and mouse cell lysates. 28595377 7 5 theme appropriate 1216:1226 arg1 controls 1228:1235 appropriate controls 1216:1235 appropriate controls 1216:1235 These non-specific signals migrate similarly to full-length OGA and are detected robustly, suggesting that the use of appropriate controls is essential to avoid the misidentification of OGA. 28595377 4 6 from lysates 705:711 arg1 enrichment 670:679 the enrichment 666:679 the enrichment of full-length OGA from lysates of mouse and human origin 666:737 To facilitate studies focused on the role of O-GlcNAc and OGA in disease, we sought to identify commercially available antibodies that enable the enrichment of full-length OGA from lysates of mouse and human origin. 28595377 6 7 theme Western 907:913 arg1 analysis 924:931 Western blotting analysis 907:931 Western blotting analysis 907:931 However, Western blotting analysis indicates that both antibodies, as well as three non-commercially available antibodies (345, 346, 352), detect full-length OGA and numerous cross-reacting proteins. 28595377 6 8 theme available 999:1007 arg1 antibodies 1009:1018 three non-commercially available antibodies 976:1018 three non-commercially available antibodies (345, 346, 352) 976:1034 However, Western blotting analysis indicates that both antibodies, as well as three non-commercially available antibodies (345, 346, 352), detect full-length OGA and numerous cross-reacting proteins. 28595377 6 9 theme cross-reacting 1073:1086 arg1 proteins 1088:1095 numerous cross-reacting proteins 1064:1095 numerous cross-reacting proteins 1064:1095 However, Western blotting analysis indicates that both antibodies, as well as three non-commercially available antibodies (345, 346, 352), detect full-length OGA and numerous cross-reacting proteins. 28595377 1 10 theme nuclear 193:199 arg1 proteins 233:240 nuclear, cytoplasmic, and mitochondrial proteins 193:240 nuclear, cytoplasmic, and mitochondrial proteins 193:240 O-linked β-N-acetylglucosamine (O-GlcNAc) is an essential regulatory post-translational modification of thousands of nuclear, cytoplasmic, and mitochondrial proteins. 28595377 1 11 theme thousands 180:188 arg1 β-N-acetylglucosamine 85:105 O-linked β-N-acetylglucosamine 76:105 O-linked β-N-acetylglucosamine (O-GlcNAc) 76:116 O-linked β-N-acetylglucosamine (O-GlcNAc) is an essential regulatory post-translational modification of thousands of nuclear, cytoplasmic, and mitochondrial proteins. 28595377 1 11 theme thousands 180:188 arg1 modification 164:175 an essential regulatory post-translational modification 121:175 an essential regulatory post-translational modification of thousands of nuclear, cytoplasmic, and mitochondrial proteins 121:240 O-linked β-N-acetylglucosamine (O-GlcNAc) is an essential regulatory post-translational modification of thousands of nuclear, cytoplasmic, and mitochondrial proteins. 28595377 7 12 theme non-specific 1104:1115 arg1 signals 1117:1123 These non-specific signals 1098:1123 These non-specific signals 1098:1123 These non-specific signals migrate similarly to full-length OGA and are detected robustly, suggesting that the use of appropriate controls is essential to avoid the misidentification of OGA. 28595377 5 13 theme mouse 878:882 arg1 lysates 889:895 human and mouse cell lysates 868:895 human and mouse cell lysates 868:895 Here, we report that antibodies from Abcam and Bethyl Laboratories can be used to immunoprecipitate OGA to near-saturation from human and mouse cell lysates. 28595377 7 14 theme controls 1228:1235 arg1 use 1209:1211 the use 1205:1211 the use of appropriate controls 1205:1235 These non-specific signals migrate similarly to full-length OGA and are detected robustly, suggesting that the use of appropriate controls is essential to avoid the misidentification of OGA. 28595377 7 14 theme controls 1228:1235 arg1 essential 1240:1248 essential 1240:1248 essential 1240:1248 These non-specific signals migrate similarly to full-length OGA and are detected robustly, suggesting that the use of appropriate controls is essential to avoid the misidentification of OGA. 28595377 6 15 theme non-commercially 982:997 arg1 antibodies 1009:1018 three non-commercially available antibodies 976:1018 three non-commercially available antibodies (345, 346, 352) 976:1034 However, Western blotting analysis indicates that both antibodies, as well as three non-commercially available antibodies (345, 346, 352), detect full-length OGA and numerous cross-reacting proteins. 28595377 1 16 theme O-linked 76:83 arg1 β-N-acetylglucosamine 85:105 O-linked β-N-acetylglucosamine 76:105 O-linked β-N-acetylglucosamine (O-GlcNAc) 76:116 O-linked β-N-acetylglucosamine (O-GlcNAc) is an essential regulatory post-translational modification of thousands of nuclear, cytoplasmic, and mitochondrial proteins. 28595377 1 16 theme O-linked 76:83 arg1 modification 164:175 an essential regulatory post-translational modification 121:175 an essential regulatory post-translational modification of thousands of nuclear, cytoplasmic, and mitochondrial proteins 121:240 O-linked β-N-acetylglucosamine (O-GlcNAc) is an essential regulatory post-translational modification of thousands of nuclear, cytoplasmic, and mitochondrial proteins. 28595377 1 16 theme O-linked 76:83 arg1 O-GlcNAc 108:115 O-GlcNAc 108:115 O-GlcNAc 108:115 O-linked β-N-acetylglucosamine (O-GlcNAc) is an essential regulatory post-translational modification of thousands of nuclear, cytoplasmic, and mitochondrial proteins. 28595377 7 17 theme OGA 1284:1286 arg1 misidentification 1263:1279 the misidentification 1259:1279 the misidentification of OGA 1259:1286 These non-specific signals migrate similarly to full-length OGA and are detected robustly, suggesting that the use of appropriate controls is essential to avoid the misidentification of OGA. 28595377 3 18 theme numerous 435:442 arg1 tumorigenesis 463:475 tumorigenesis 463:475 tumorigenesis 463:475 Dysregulation of O-GlcNAc-cycling is implicated in the etiology of numerous diseases including tumorigenesis, metabolic dysfunction, and neurodegeneration. 28595377 3 18 theme numerous 435:442 arg1 dysfunction 488:498 metabolic dysfunction 478:498 metabolic dysfunction 478:498 Dysregulation of O-GlcNAc-cycling is implicated in the etiology of numerous diseases including tumorigenesis, metabolic dysfunction, and neurodegeneration. 28595377 3 18 theme numerous 435:442 arg1 diseases 444:451 numerous diseases 435:451 numerous diseases including tumorigenesis, metabolic dysfunction, and neurodegeneration 435:521 Dysregulation of O-GlcNAc-cycling is implicated in the etiology of numerous diseases including tumorigenesis, metabolic dysfunction, and neurodegeneration. 28595377 3 18 theme numerous 435:442 arg1 neurodegeneration 505:521 neurodegeneration 505:521 neurodegeneration 505:521 Dysregulation of O-GlcNAc-cycling is implicated in the etiology of numerous diseases including tumorigenesis, metabolic dysfunction, and neurodegeneration. 28595377 4 19 theme OGA 582:584 arg1 role 561:564 the role 557:564 the role of O-GlcNAc and OGA in disease 557:595 To facilitate studies focused on the role of O-GlcNAc and OGA in disease, we sought to identify commercially available antibodies that enable the enrichment of full-length OGA from lysates of mouse and human origin. 28595377 4 20 theme OGA 696:698 arg1 enrichment 670:679 the enrichment 666:679 the enrichment of full-length OGA from lysates of mouse and human origin 666:737 To facilitate studies focused on the role of O-GlcNAc and OGA in disease, we sought to identify commercially available antibodies that enable the enrichment of full-length OGA from lysates of mouse and human origin. 28595377 5 21 theme immunoprecipitate 822:838 arg1 OGA 840:842 immunoprecipitate OGA 822:842 immunoprecipitate OGA to near-saturation from human and mouse cell lysates 822:895 Here, we report that antibodies from Abcam and Bethyl Laboratories can be used to immunoprecipitate OGA to near-saturation from human and mouse cell lysates. 28595377 1 22 theme cytoplasmic 202:212 arg1 proteins 233:240 nuclear, cytoplasmic, and mitochondrial proteins 193:240 nuclear, cytoplasmic, and mitochondrial proteins 193:240 O-linked β-N-acetylglucosamine (O-GlcNAc) is an essential regulatory post-translational modification of thousands of nuclear, cytoplasmic, and mitochondrial proteins. 28595377 3 23 theme O-GlcNAc-cycling 385:400 arg1 Dysregulation 368:380 Dysregulation 368:380 Dysregulation of O-GlcNAc-cycling 368:400 Dysregulation of O-GlcNAc-cycling is implicated in the etiology of numerous diseases including tumorigenesis, metabolic dysfunction, and neurodegeneration. 28595377 2 24 theme O-GlcNAc 306:313 arg1 transferase 315:325 the O-GlcNAc transferase 302:325 the O-GlcNAc transferase 302:325 O-GlcNAc is dynamically added and removed from proteins by the O-GlcNAc transferase and the O-GlcNAcase (OGA), respectively. 28595377 5 25 theme Bethyl 787:792 arg1 Laboratories 794:805 Abcam and Bethyl Laboratories 777:805 Abcam and Bethyl Laboratories 777:805 Here, we report that antibodies from Abcam and Bethyl Laboratories can be used to immunoprecipitate OGA to near-saturation from human and mouse cell lysates. 28595377 0 26 dep human 47:51 arg1 O-GlcNAcase 63:73 O-GlcNAcase 63:73 O-GlcNAcase 63:73 Characterization of tools to detect and enrich human and mouse O-GlcNAcase. 28595377 3 27 theme diseases 444:451 arg1 etiology 423:430 the etiology 419:430 the etiology of numerous diseases including tumorigenesis, metabolic dysfunction, and neurodegeneration 419:521 Dysregulation of O-GlcNAc-cycling is implicated in the etiology of numerous diseases including tumorigenesis, metabolic dysfunction, and neurodegeneration. 28595377 4 28 theme full-length 684:694 arg1 OGA 696:698 full-length OGA 684:698 full-length OGA 684:698 To facilitate studies focused on the role of O-GlcNAc and OGA in disease, we sought to identify commercially available antibodies that enable the enrichment of full-length OGA from lysates of mouse and human origin. 28595377 5 29 theme cell 884:887 arg1 lysates 889:895 human and mouse cell lysates 868:895 human and mouse cell lysates 868:895 Here, we report that antibodies from Abcam and Bethyl Laboratories can be used to immunoprecipitate OGA to near-saturation from human and mouse cell lysates. 28595377 5 30 theme human 868:872 arg1 lysates 889:895 human and mouse cell lysates 868:895 human and mouse cell lysates 868:895 Here, we report that antibodies from Abcam and Bethyl Laboratories can be used to immunoprecipitate OGA to near-saturation from human and mouse cell lysates. 28595377 1 31 theme mitochondrial 219:231 arg1 proteins 233:240 nuclear, cytoplasmic, and mitochondrial proteins 193:240 nuclear, cytoplasmic, and mitochondrial proteins 193:240 O-linked β-N-acetylglucosamine (O-GlcNAc) is an essential regulatory post-translational modification of thousands of nuclear, cytoplasmic, and mitochondrial proteins. 28595377 4 32 from role 561:564 arg1 disease 589:595 disease 589:595 disease 589:595 To facilitate studies focused on the role of O-GlcNAc and OGA in disease, we sought to identify commercially available antibodies that enable the enrichment of full-length OGA from lysates of mouse and human origin. 28595377 4 33 theme origin 732:737 arg1 lysates 705:711 lysates 705:711 lysates of mouse and human origin 705:737 To facilitate studies focused on the role of O-GlcNAc and OGA in disease, we sought to identify commercially available antibodies that enable the enrichment of full-length OGA from lysates of mouse and human origin. 28595377 6 34 theme blotting 915:922 arg1 analysis 924:931 Western blotting analysis 907:931 Western blotting analysis 907:931 However, Western blotting analysis indicates that both antibodies, as well as three non-commercially available antibodies (345, 346, 352), detect full-length OGA and numerous cross-reacting proteins. 28595377 4 35 theme O-GlcNAc 569:576 arg1 role 561:564 the role 557:564 the role of O-GlcNAc and OGA in disease 557:595 To facilitate studies focused on the role of O-GlcNAc and OGA in disease, we sought to identify commercially available antibodies that enable the enrichment of full-length OGA from lysates of mouse and human origin. 28595377 4 36 theme human 726:730 arg1 origin 732:737 human origin 726:737 human origin 726:737 To facilitate studies focused on the role of O-GlcNAc and OGA in disease, we sought to identify commercially available antibodies that enable the enrichment of full-length OGA from lysates of mouse and human origin. 28595377 1 37 theme proteins 233:240 arg1 thousands 180:188 thousands 180:188 thousands of nuclear, cytoplasmic, and mitochondrial proteins 180:240 O-linked β-N-acetylglucosamine (O-GlcNAc) is an essential regulatory post-translational modification of thousands of nuclear, cytoplasmic, and mitochondrial proteins. 28595377 5 38 used used 814:817 arg2 antibodies 761:770 antibodies 761:770 antibodies from Abcam and Bethyl Laboratories 761:805 Here, we report that antibodies from Abcam and Bethyl Laboratories can be used to immunoprecipitate OGA to near-saturation from human and mouse cell lysates. 28595377 1 39 theme essential 124:132 arg1 β-N-acetylglucosamine 85:105 O-linked β-N-acetylglucosamine 76:105 O-linked β-N-acetylglucosamine (O-GlcNAc) 76:116 O-linked β-N-acetylglucosamine (O-GlcNAc) is an essential regulatory post-translational modification of thousands of nuclear, cytoplasmic, and mitochondrial proteins. 28595377 1 39 theme essential 124:132 arg1 modification 164:175 an essential regulatory post-translational modification 121:175 an essential regulatory post-translational modification of thousands of nuclear, cytoplasmic, and mitochondrial proteins 121:240 O-linked β-N-acetylglucosamine (O-GlcNAc) is an essential regulatory post-translational modification of thousands of nuclear, cytoplasmic, and mitochondrial proteins. 28595377 2 40 attach removed 277:283 arg1 proteins 290:297 proteins 290:297 proteins 290:297 O-GlcNAc is dynamically added and removed from proteins by the O-GlcNAc transferase and the O-GlcNAcase (OGA), respectively. 28595377 2 40 attach removed 277:283 arg2 O-GlcNAc 243:250 O-GlcNAc 243:250 O-GlcNAc 243:250 O-GlcNAc is dynamically added and removed from proteins by the O-GlcNAc transferase and the O-GlcNAcase (OGA), respectively. 28595377 3 41 theme metabolic 478:486 arg1 dysfunction 488:498 metabolic dysfunction 478:498 metabolic dysfunction 478:498 Dysregulation of O-GlcNAc-cycling is implicated in the etiology of numerous diseases including tumorigenesis, metabolic dysfunction, and neurodegeneration. 28595377 5 42 from lysates 889:895 arg1 OGA 840:842 immunoprecipitate OGA 822:842 immunoprecipitate OGA to near-saturation from human and mouse cell lysates 822:895 Here, we report that antibodies from Abcam and Bethyl Laboratories can be used to immunoprecipitate OGA to near-saturation from human and mouse cell lysates. 28595377 1 43 theme regulatory 134:143 arg1 β-N-acetylglucosamine 85:105 O-linked β-N-acetylglucosamine 76:105 O-linked β-N-acetylglucosamine (O-GlcNAc) 76:116 O-linked β-N-acetylglucosamine (O-GlcNAc) is an essential regulatory post-translational modification of thousands of nuclear, cytoplasmic, and mitochondrial proteins. 28595377 1 43 theme regulatory 134:143 arg1 modification 164:175 an essential regulatory post-translational modification 121:175 an essential regulatory post-translational modification of thousands of nuclear, cytoplasmic, and mitochondrial proteins 121:240 O-linked β-N-acetylglucosamine (O-GlcNAc) is an essential regulatory post-translational modification of thousands of nuclear, cytoplasmic, and mitochondrial proteins. 28595377 6 44 theme numerous 1064:1071 arg1 proteins 1088:1095 numerous cross-reacting proteins 1064:1095 numerous cross-reacting proteins 1064:1095 However, Western blotting analysis indicates that both antibodies, as well as three non-commercially available antibodies (345, 346, 352), detect full-length OGA and numerous cross-reacting proteins. 28595377 7 45 theme full-length 1146:1156 arg1 OGA 1158:1160 full-length OGA 1146:1160 full-length OGA 1146:1160 These non-specific signals migrate similarly to full-length OGA and are detected robustly, suggesting that the use of appropriate controls is essential to avoid the misidentification of OGA. 28595377 6 46 dep antibodies 1009:1018 arg1 352 1031:1033 352 1031:1033 352 1031:1033 However, Western blotting analysis indicates that both antibodies, as well as three non-commercially available antibodies (345, 346, 352), detect full-length OGA and numerous cross-reacting proteins. 28595377 0 47 theme tools 20:24 arg1 Characterization 0:15 Characterization 0:15 Characterization of tools 0:24 Characterization of tools to detect and enrich human and mouse O-GlcNAcase. 28595377 1 48 theme post-translational 145:162 arg1 β-N-acetylglucosamine 85:105 O-linked β-N-acetylglucosamine 76:105 O-linked β-N-acetylglucosamine (O-GlcNAc) 76:116 O-linked β-N-acetylglucosamine (O-GlcNAc) is an essential regulatory post-translational modification of thousands of nuclear, cytoplasmic, and mitochondrial proteins. 28595377 1 48 theme post-translational 145:162 arg1 modification 164:175 an essential regulatory post-translational modification 121:175 an essential regulatory post-translational modification of thousands of nuclear, cytoplasmic, and mitochondrial proteins 121:240 O-linked β-N-acetylglucosamine (O-GlcNAc) is an essential regulatory post-translational modification of thousands of nuclear, cytoplasmic, and mitochondrial proteins. 28595377 4 49 theme available 633:641 arg1 antibodies 643:652 commercially available antibodies 620:652 commercially available antibodies that enable the enrichment of full-length OGA from lysates of mouse and human origin 620:737 To facilitate studies focused on the role of O-GlcNAc and OGA in disease, we sought to identify commercially available antibodies that enable the enrichment of full-length OGA from lysates of mouse and human origin. 27272618 5 0 theme transcriptional 835:849 arg1 control 851:857 FACT-driven transcriptional control 823:857 FACT-driven transcriptional control 823:857 Preferential binding of FACT to GlcNAcylated nucleosomes may point towards O-GlcNAcylation as one of the triggers for FACT-driven transcriptional control. 27272618 5 1 theme triggers 810:817 arg1 one 799:801 one 799:801 one 799:801 Preferential binding of FACT to GlcNAcylated nucleosomes may point towards O-GlcNAcylation as one of the triggers for FACT-driven transcriptional control. 27272618 5 1 theme triggers 810:817 arg1 triggers 810:817 the triggers 806:817 the triggers for FACT-driven transcriptional control 806:857 Preferential binding of FACT to GlcNAcylated nucleosomes may point towards O-GlcNAcylation as one of the triggers for FACT-driven transcriptional control. 27272618 1 2 theme chromosomal 270:280 arg1 DNA 282:284 chromosomal DNA 270:284 chromosomal DNA 270:284 Transcriptional regulation can be established by various post-translational modifications (PTMs) on histone proteins in the nucleosome and by nucleobase modifications on chromosomal DNA. 27272618 0 3 theme FACT 86:89 arg1 Complex 91:97 the FACT Complex 82:97 the FACT Complex 82:97 Synthetic Nucleosomes Reveal that GlcNAcylation Modulates Direct Interaction with the FACT Complex. 27272618 5 4 theme FACT 729:732 arg1 binding 718:724 Preferential binding 705:724 Preferential binding of FACT to GlcNAcylated nucleosomes 705:760 Preferential binding of FACT to GlcNAcylated nucleosomes may point towards O-GlcNAcylation as one of the triggers for FACT-driven transcriptional control. 27272618 2 5 theme O-GlcNAcylation 322:336 arg1 consequences 298:309 Functional consequences 287:309 Functional consequences of histone O-GlcNAcylation (O-GlcNAc=O-linked β-N-acetylglucosamine) 287:378 Functional consequences of histone O-GlcNAcylation (O-GlcNAc=O-linked β-N-acetylglucosamine) are largely unexplored. 27272618 4 6 dep complex 696:702 arg1 facilitates 652:662 facilitates 652:662 facilitates 652:662 Mass-spectrometry-based quantitative interaction proteomics reveals a direct interaction between GlcNAcylated nucleosomes and the "facilitates chromatin transcription" (FACT) complex. 27272618 5 7 theme GlcNAcylated 737:748 arg1 nucleosomes 750:760 GlcNAcylated nucleosomes 737:760 GlcNAcylated nucleosomes 737:760 Preferential binding of FACT to GlcNAcylated nucleosomes may point towards O-GlcNAcylation as one of the triggers for FACT-driven transcriptional control. 27272618 2 8 theme histone 314:320 arg1 O-GlcNAcylation 322:336 histone O-GlcNAcylation 314:336 histone O-GlcNAcylation (O-GlcNAc=O-linked β-N-acetylglucosamine) 314:378 Functional consequences of histone O-GlcNAcylation (O-GlcNAc=O-linked β-N-acetylglucosamine) are largely unexplored. 27272618 2 8 theme histone 314:320 arg1 β-N-acetylglucosamine 357:377 O-GlcNAc=O-linked β-N-acetylglucosamine 339:377 O-GlcNAc=O-linked β-N-acetylglucosamine 339:377 Functional consequences of histone O-GlcNAcylation (O-GlcNAc=O-linked β-N-acetylglucosamine) are largely unexplored. 27272618 4 9 theme direct 591:596 arg1 interaction 598:608 a direct interaction 589:608 a direct interaction between GlcNAcylated nucleosomes and the "facilitates chromatin transcription" (FACT) complex 589:702 Mass-spectrometry-based quantitative interaction proteomics reveals a direct interaction between GlcNAcylated nucleosomes and the "facilitates chromatin transcription" (FACT) complex. 27272618 1 10 from modifications 176:188 arg1 proteins 208:215 histone proteins 200:215 histone proteins in the nucleosome and by nucleobase modifications on chromosomal DNA 200:284 Transcriptional regulation can be established by various post-translational modifications (PTMs) on histone proteins in the nucleosome and by nucleobase modifications on chromosomal DNA. 27272618 4 11 theme GlcNAcylated 618:629 arg1 nucleosomes 631:641 GlcNAcylated nucleosomes 618:641 GlcNAcylated nucleosomes 618:641 Mass-spectrometry-based quantitative interaction proteomics reveals a direct interaction between GlcNAcylated nucleosomes and the "facilitates chromatin transcription" (FACT) complex. 27272618 5 12 theme Preferential 705:716 arg1 binding 718:724 Preferential binding 705:724 Preferential binding of FACT to GlcNAcylated nucleosomes 705:760 Preferential binding of FACT to GlcNAcylated nucleosomes may point towards O-GlcNAcylation as one of the triggers for FACT-driven transcriptional control. 27272618 1 13 theme histone 200:206 arg1 proteins 208:215 histone proteins 200:215 histone proteins in the nucleosome and by nucleobase modifications on chromosomal DNA 200:284 Transcriptional regulation can be established by various post-translational modifications (PTMs) on histone proteins in the nucleosome and by nucleobase modifications on chromosomal DNA. 27272618 0 14 theme Synthetic 0:8 arg1 Nucleosomes 10:20 Synthetic Nucleosomes 0:20 Synthetic Nucleosomes 0:20 Synthetic Nucleosomes Reveal that GlcNAcylation Modulates Direct Interaction with the FACT Complex. 27272618 4 15 theme FACT 690:693 arg1 complex 696:702 the "facilitates chromatin transcription" (FACT) complex 647:702 the "facilitates chromatin transcription" (FACT) complex 647:702 Mass-spectrometry-based quantitative interaction proteomics reveals a direct interaction between GlcNAcylated nucleosomes and the "facilitates chromatin transcription" (FACT) complex. 27272618 1 16 theme Transcriptional 100:114 arg1 regulation 116:125 Transcriptional regulation 100:125 Transcriptional regulation 100:125 Transcriptional regulation can be established by various post-translational modifications (PTMs) on histone proteins in the nucleosome and by nucleobase modifications on chromosomal DNA. 27272618 2 17 theme O-GlcNAc=O-linked 339:355 arg1 O-GlcNAcylation 322:336 histone O-GlcNAcylation 314:336 histone O-GlcNAcylation (O-GlcNAc=O-linked β-N-acetylglucosamine) 314:378 Functional consequences of histone O-GlcNAcylation (O-GlcNAc=O-linked β-N-acetylglucosamine) are largely unexplored. 27272618 2 17 theme O-GlcNAc=O-linked 339:355 arg1 β-N-acetylglucosamine 357:377 O-GlcNAc=O-linked β-N-acetylglucosamine 339:377 O-GlcNAc=O-linked β-N-acetylglucosamine 339:377 Functional consequences of histone O-GlcNAcylation (O-GlcNAc=O-linked β-N-acetylglucosamine) are largely unexplored. 27272618 3 18 theme chemical 479:486 arg1 modification 507:518 chemical post-translational modification 479:518 chemical post-translational modification 479:518 Herein, we generate homogeneously GlcNAcylated histones and nucleosomes by chemical post-translational modification. 27272618 4 19 theme interaction 558:568 arg1 proteomics 570:579 Mass-spectrometry-based quantitative interaction proteomics 521:579 Mass-spectrometry-based quantitative interaction proteomics 521:579 Mass-spectrometry-based quantitative interaction proteomics reveals a direct interaction between GlcNAcylated nucleosomes and the "facilitates chromatin transcription" (FACT) complex. 27272618 3 20 theme post-translational 488:505 arg1 modification 507:518 chemical post-translational modification 479:518 chemical post-translational modification 479:518 Herein, we generate homogeneously GlcNAcylated histones and nucleosomes by chemical post-translational modification. 27272618 4 21 theme chromatin 664:672 arg1 complex 696:702 the "facilitates chromatin transcription" (FACT) complex 647:702 the "facilitates chromatin transcription" (FACT) complex 647:702 Mass-spectrometry-based quantitative interaction proteomics reveals a direct interaction between GlcNAcylated nucleosomes and the "facilitates chromatin transcription" (FACT) complex. 27272618 2 22 link O-GlcNAc=O-linked 339:355 arg1 O-GlcNAcylation 322:336 histone O-GlcNAcylation 314:336 histone O-GlcNAcylation (O-GlcNAc=O-linked β-N-acetylglucosamine) 314:378 Functional consequences of histone O-GlcNAcylation (O-GlcNAc=O-linked β-N-acetylglucosamine) are largely unexplored. 27272618 2 22 link O-GlcNAc=O-linked 339:355 arg1 β-N-acetylglucosamine 357:377 O-GlcNAc=O-linked β-N-acetylglucosamine 339:377 O-GlcNAc=O-linked β-N-acetylglucosamine 339:377 Functional consequences of histone O-GlcNAcylation (O-GlcNAc=O-linked β-N-acetylglucosamine) are largely unexplored. 27272618 1 23 from modifications 253:265 arg1 DNA 282:284 chromosomal DNA 270:284 chromosomal DNA 270:284 Transcriptional regulation can be established by various post-translational modifications (PTMs) on histone proteins in the nucleosome and by nucleobase modifications on chromosomal DNA. 27272618 0 24 theme Direct 58:63 arg1 Interaction 65:75 Direct Interaction 58:75 Direct Interaction with the FACT Complex 58:97 Synthetic Nucleosomes Reveal that GlcNAcylation Modulates Direct Interaction with the FACT Complex. 27272618 4 25 theme " 687:687 arg1 complex 696:702 the "facilitates chromatin transcription" (FACT) complex 647:702 the "facilitates chromatin transcription" (FACT) complex 647:702 Mass-spectrometry-based quantitative interaction proteomics reveals a direct interaction between GlcNAcylated nucleosomes and the "facilitates chromatin transcription" (FACT) complex. 27272618 4 26 theme transcription 674:686 arg1 complex 696:702 the "facilitates chromatin transcription" (FACT) complex 647:702 the "facilitates chromatin transcription" (FACT) complex 647:702 Mass-spectrometry-based quantitative interaction proteomics reveals a direct interaction between GlcNAcylated nucleosomes and the "facilitates chromatin transcription" (FACT) complex. 27272618 5 27 theme FACT-driven 823:833 arg1 control 851:857 FACT-driven transcriptional control 823:857 FACT-driven transcriptional control 823:857 Preferential binding of FACT to GlcNAcylated nucleosomes may point towards O-GlcNAcylation as one of the triggers for FACT-driven transcriptional control. 27272618 2 28 theme Functional 287:296 arg1 consequences 298:309 Functional consequences 287:309 Functional consequences of histone O-GlcNAcylation (O-GlcNAc=O-linked β-N-acetylglucosamine) 287:378 Functional consequences of histone O-GlcNAcylation (O-GlcNAc=O-linked β-N-acetylglucosamine) are largely unexplored. 27272618 3 29 dep generate 415:422 arg1 GlcNAcylated 438:449 GlcNAcylated 438:449 generate homogeneously GlcNAcylated histones and nucleosomes by chemical post-translational modification 415:518 Herein, we generate homogeneously GlcNAcylated histones and nucleosomes by chemical post-translational modification. 27272618 4 30 theme quantitative 545:556 arg1 proteomics 570:579 Mass-spectrometry-based quantitative interaction proteomics 521:579 Mass-spectrometry-based quantitative interaction proteomics 521:579 Mass-spectrometry-based quantitative interaction proteomics reveals a direct interaction between GlcNAcylated nucleosomes and the "facilitates chromatin transcription" (FACT) complex. 27272618 0 31 with Interaction 65:75 arg1 Complex 91:97 the FACT Complex 82:97 the FACT Complex 82:97 Synthetic Nucleosomes Reveal that GlcNAcylation Modulates Direct Interaction with the FACT Complex. 27272618 1 32 theme various 149:155 arg1 modifications 176:188 various post-translational modifications 149:188 various post-translational modifications (PTMs) on histone proteins in the nucleosome and by nucleobase modifications on chromosomal DNA 149:284 Transcriptional regulation can be established by various post-translational modifications (PTMs) on histone proteins in the nucleosome and by nucleobase modifications on chromosomal DNA. 27272618 1 32 theme various 149:155 arg1 PTMs 191:194 PTMs 191:194 PTMs 191:194 Transcriptional regulation can be established by various post-translational modifications (PTMs) on histone proteins in the nucleosome and by nucleobase modifications on chromosomal DNA. 27272618 1 33 theme nucleobase 242:251 arg1 modifications 253:265 nucleobase modifications 242:265 nucleobase modifications on chromosomal DNA 242:284 Transcriptional regulation can be established by various post-translational modifications (PTMs) on histone proteins in the nucleosome and by nucleobase modifications on chromosomal DNA. 27272618 4 34 theme Mass-spectrometry-based 521:543 arg1 proteomics 570:579 Mass-spectrometry-based quantitative interaction proteomics 521:579 Mass-spectrometry-based quantitative interaction proteomics 521:579 Mass-spectrometry-based quantitative interaction proteomics reveals a direct interaction between GlcNAcylated nucleosomes and the "facilitates chromatin transcription" (FACT) complex. 27272618 1 35 from proteins 208:215 arg1 nucleosome 224:233 the nucleosome 220:233 the nucleosome 220:233 Transcriptional regulation can be established by various post-translational modifications (PTMs) on histone proteins in the nucleosome and by nucleobase modifications on chromosomal DNA. 27272618 1 36 theme post-translational 157:174 arg1 modifications 176:188 various post-translational modifications 149:188 various post-translational modifications (PTMs) on histone proteins in the nucleosome and by nucleobase modifications on chromosomal DNA 149:284 Transcriptional regulation can be established by various post-translational modifications (PTMs) on histone proteins in the nucleosome and by nucleobase modifications on chromosomal DNA. 27272618 1 36 theme post-translational 157:174 arg1 PTMs 191:194 PTMs 191:194 PTMs 191:194 Transcriptional regulation can be established by various post-translational modifications (PTMs) on histone proteins in the nucleosome and by nucleobase modifications on chromosomal DNA. 25607533 2 0 theme antimicrobial 484:496 arg1 activity 498:505 antimicrobial activity 484:505 antimicrobial activity 484:505 The synthetic and naturally occurring peptides were compared by HPLC, mass spectrometry, NMR and CD spectroscopy, and their stability towards chymotrypsin digestion and antimicrobial activity were measured. 25607533 1 1 theme rare 165:168 arg1 moiety 208:213 a rare S-linked N-acetylglucosamine (GlcNAc) moiety 163:213 a rare S-linked N-acetylglucosamine (GlcNAc) moiety 163:213 The first total synthesis of glycocin F, a uniquely diglycosylated antimicrobial peptide bearing a rare S-linked N-acetylglucosamine (GlcNAc) moiety in addition to an O-linked GlcNAc, has been accomplished using a native chemical ligation strategy. 25607533 3 2 theme synthetic 640:648 arg1 analogue 650:657 an active synthetic analogue 630:657 an active synthetic analogue 630:657 This is the first comprehensive structural and functional comparison of a naturally occurring glycocin with an active synthetic analogue. 25607533 3 3 theme comprehensive 540:552 arg1 This 522:525 This 522:525 This 522:525 This is the first comprehensive structural and functional comparison of a naturally occurring glycocin with an active synthetic analogue. 25607533 3 3 theme comprehensive 540:552 arg1 comparison 580:589 the first comprehensive structural and functional comparison 530:589 the first comprehensive structural and functional comparison of a naturally occurring glycocin with an active synthetic analogue 530:657 This is the first comprehensive structural and functional comparison of a naturally occurring glycocin with an active synthetic analogue. 25607533 3 4 theme structural 554:563 arg1 This 522:525 This 522:525 This 522:525 This is the first comprehensive structural and functional comparison of a naturally occurring glycocin with an active synthetic analogue. 25607533 3 4 theme structural 554:563 arg1 comparison 580:589 the first comprehensive structural and functional comparison 530:589 the first comprehensive structural and functional comparison of a naturally occurring glycocin with an active synthetic analogue 530:657 This is the first comprehensive structural and functional comparison of a naturally occurring glycocin with an active synthetic analogue. 25607533 2 5 theme synthetic 319:327 arg1 peptides 353:360 The synthetic and naturally occurring peptides 315:360 The synthetic and naturally occurring peptides 315:360 The synthetic and naturally occurring peptides were compared by HPLC, mass spectrometry, NMR and CD spectroscopy, and their stability towards chymotrypsin digestion and antimicrobial activity were measured. 25607533 1 6 theme first 70:74 arg1 synthesis 82:90 The first total synthesis 66:90 The first total synthesis of glycocin F, a uniquely diglycosylated antimicrobial peptide bearing a rare S-linked N-acetylglucosamine (GlcNAc) moiety in addition to an O-linked GlcNAc, 66:248 The first total synthesis of glycocin F, a uniquely diglycosylated antimicrobial peptide bearing a rare S-linked N-acetylglucosamine (GlcNAc) moiety in addition to an O-linked GlcNAc, has been accomplished using a native chemical ligation strategy. 25607533 1 7 theme S-linked 170:177 arg1 moiety 208:213 a rare S-linked N-acetylglucosamine (GlcNAc) moiety 163:213 a rare S-linked N-acetylglucosamine (GlcNAc) moiety 163:213 The first total synthesis of glycocin F, a uniquely diglycosylated antimicrobial peptide bearing a rare S-linked N-acetylglucosamine (GlcNAc) moiety in addition to an O-linked GlcNAc, has been accomplished using a native chemical ligation strategy. 25607533 1 8 link O-linked 233:240 arg1 GlcNAc 242:247 an O-linked GlcNAc 230:247 an O-linked GlcNAc 230:247 The first total synthesis of glycocin F, a uniquely diglycosylated antimicrobial peptide bearing a rare S-linked N-acetylglucosamine (GlcNAc) moiety in addition to an O-linked GlcNAc, has been accomplished using a native chemical ligation strategy. 25607533 1 9 theme total 76:80 arg1 synthesis 82:90 The first total synthesis 66:90 The first total synthesis of glycocin F, a uniquely diglycosylated antimicrobial peptide bearing a rare S-linked N-acetylglucosamine (GlcNAc) moiety in addition to an O-linked GlcNAc, 66:248 The first total synthesis of glycocin F, a uniquely diglycosylated antimicrobial peptide bearing a rare S-linked N-acetylglucosamine (GlcNAc) moiety in addition to an O-linked GlcNAc, has been accomplished using a native chemical ligation strategy. 25607533 1 10 theme N-acetylglucosamine 179:197 arg1 moiety 208:213 a rare S-linked N-acetylglucosamine (GlcNAc) moiety 163:213 a rare S-linked N-acetylglucosamine (GlcNAc) moiety 163:213 The first total synthesis of glycocin F, a uniquely diglycosylated antimicrobial peptide bearing a rare S-linked N-acetylglucosamine (GlcNAc) moiety in addition to an O-linked GlcNAc, has been accomplished using a native chemical ligation strategy. 25607533 1 11 link S-linked 170:177 arg1 moiety 208:213 a rare S-linked N-acetylglucosamine (GlcNAc) moiety 163:213 a rare S-linked N-acetylglucosamine (GlcNAc) moiety 163:213 The first total synthesis of glycocin F, a uniquely diglycosylated antimicrobial peptide bearing a rare S-linked N-acetylglucosamine (GlcNAc) moiety in addition to an O-linked GlcNAc, has been accomplished using a native chemical ligation strategy. 25607533 1 12 theme GlcNAc 200:205 arg1 moiety 208:213 a rare S-linked N-acetylglucosamine (GlcNAc) moiety 163:213 a rare S-linked N-acetylglucosamine (GlcNAc) moiety 163:213 The first total synthesis of glycocin F, a uniquely diglycosylated antimicrobial peptide bearing a rare S-linked N-acetylglucosamine (GlcNAc) moiety in addition to an O-linked GlcNAc, has been accomplished using a native chemical ligation strategy. 25607533 0 13 theme antimicrobial 17:29 arg1 glycopeptide 40:51 the antimicrobial S-linked glycopeptide 13:51 the antimicrobial S-linked glycopeptide 13:51 Synthesis of the antimicrobial S-linked glycopeptide, glycocin F. 25607533 0 14 link S-linked 31:38 arg1 glycopeptide 40:51 the antimicrobial S-linked glycopeptide 13:51 the antimicrobial S-linked glycopeptide 13:51 Synthesis of the antimicrobial S-linked glycopeptide, glycocin F. 25607533 1 15 theme glycocin F 95:104 arg1 synthesis 82:90 The first total synthesis 66:90 The first total synthesis of glycocin F, a uniquely diglycosylated antimicrobial peptide bearing a rare S-linked N-acetylglucosamine (GlcNAc) moiety in addition to an O-linked GlcNAc, 66:248 The first total synthesis of glycocin F, a uniquely diglycosylated antimicrobial peptide bearing a rare S-linked N-acetylglucosamine (GlcNAc) moiety in addition to an O-linked GlcNAc, has been accomplished using a native chemical ligation strategy. 25607533 2 16 theme CD 412:413 arg1 spectroscopy 415:426 CD spectroscopy 412:426 CD spectroscopy 412:426 The synthetic and naturally occurring peptides were compared by HPLC, mass spectrometry, NMR and CD spectroscopy, and their stability towards chymotrypsin digestion and antimicrobial activity were measured. 25607533 1 17 theme native 280:285 arg1 strategy 305:312 a native chemical ligation strategy 278:312 a native chemical ligation strategy 278:312 The first total synthesis of glycocin F, a uniquely diglycosylated antimicrobial peptide bearing a rare S-linked N-acetylglucosamine (GlcNAc) moiety in addition to an O-linked GlcNAc, has been accomplished using a native chemical ligation strategy. 25607533 3 18 theme functional 569:578 arg1 This 522:525 This 522:525 This 522:525 This is the first comprehensive structural and functional comparison of a naturally occurring glycocin with an active synthetic analogue. 25607533 3 18 theme functional 569:578 arg1 comparison 580:589 the first comprehensive structural and functional comparison 530:589 the first comprehensive structural and functional comparison of a naturally occurring glycocin with an active synthetic analogue 530:657 This is the first comprehensive structural and functional comparison of a naturally occurring glycocin with an active synthetic analogue. 25607533 0 19 theme glycopeptide 40:51 arg1 Synthesis 0:8 Synthesis 0:8 Synthesis 0:8 Synthesis of the antimicrobial S-linked glycopeptide, glycocin F. 25607533 1 20 theme chemical 287:294 arg1 strategy 305:312 a native chemical ligation strategy 278:312 a native chemical ligation strategy 278:312 The first total synthesis of glycocin F, a uniquely diglycosylated antimicrobial peptide bearing a rare S-linked N-acetylglucosamine (GlcNAc) moiety in addition to an O-linked GlcNAc, has been accomplished using a native chemical ligation strategy. 25607533 3 21 theme occurring 606:614 arg1 glycocin 616:623 a naturally occurring glycocin 594:623 a naturally occurring glycocin 594:623 This is the first comprehensive structural and functional comparison of a naturally occurring glycocin with an active synthetic analogue. 25607533 0 22 theme S-linked 31:38 arg1 glycopeptide 40:51 the antimicrobial S-linked glycopeptide 13:51 the antimicrobial S-linked glycopeptide 13:51 Synthesis of the antimicrobial S-linked glycopeptide, glycocin F. 25607533 1 23 theme ligation 296:303 arg1 strategy 305:312 a native chemical ligation strategy 278:312 a native chemical ligation strategy 278:312 The first total synthesis of glycocin F, a uniquely diglycosylated antimicrobial peptide bearing a rare S-linked N-acetylglucosamine (GlcNAc) moiety in addition to an O-linked GlcNAc, has been accomplished using a native chemical ligation strategy. 25607533 2 24 theme chymotrypsin 457:468 arg1 digestion 470:478 chymotrypsin digestion 457:478 chymotrypsin digestion 457:478 The synthetic and naturally occurring peptides were compared by HPLC, mass spectrometry, NMR and CD spectroscopy, and their stability towards chymotrypsin digestion and antimicrobial activity were measured. 25607533 3 25 theme glycocin 616:623 arg1 This 522:525 This 522:525 This 522:525 This is the first comprehensive structural and functional comparison of a naturally occurring glycocin with an active synthetic analogue. 25607533 3 25 theme glycocin 616:623 arg1 comparison 580:589 the first comprehensive structural and functional comparison 530:589 the first comprehensive structural and functional comparison of a naturally occurring glycocin with an active synthetic analogue 530:657 This is the first comprehensive structural and functional comparison of a naturally occurring glycocin with an active synthetic analogue. 25607533 2 26 theme occurring 343:351 arg1 peptides 353:360 The synthetic and naturally occurring peptides 315:360 The synthetic and naturally occurring peptides 315:360 The synthetic and naturally occurring peptides were compared by HPLC, mass spectrometry, NMR and CD spectroscopy, and their stability towards chymotrypsin digestion and antimicrobial activity were measured. 25607533 1 27 gly diglycosylated 118:131 arg1 glycocin F 95:104 glycocin F 95:104 glycocin F 95:104 The first total synthesis of glycocin F, a uniquely diglycosylated antimicrobial peptide bearing a rare S-linked N-acetylglucosamine (GlcNAc) moiety in addition to an O-linked GlcNAc, has been accomplished using a native chemical ligation strategy. 25607533 1 27 gly diglycosylated 118:131 arg1 peptide 147:153 a uniquely diglycosylated antimicrobial peptide 107:153 a uniquely diglycosylated antimicrobial peptide bearing a rare S-linked N-acetylglucosamine (GlcNAc) moiety in addition to an O-linked GlcNAc 107:247 The first total synthesis of glycocin F, a uniquely diglycosylated antimicrobial peptide bearing a rare S-linked N-acetylglucosamine (GlcNAc) moiety in addition to an O-linked GlcNAc, has been accomplished using a native chemical ligation strategy. 25607533 3 28 with comparison 580:589 arg1 analogue 650:657 an active synthetic analogue 630:657 an active synthetic analogue 630:657 This is the first comprehensive structural and functional comparison of a naturally occurring glycocin with an active synthetic analogue. 25607533 3 29 theme active 633:638 arg1 analogue 650:657 an active synthetic analogue 630:657 an active synthetic analogue 630:657 This is the first comprehensive structural and functional comparison of a naturally occurring glycocin with an active synthetic analogue. 25607533 1 30 theme diglycosylated 118:131 arg1 glycocin F 95:104 glycocin F 95:104 glycocin F 95:104 The first total synthesis of glycocin F, a uniquely diglycosylated antimicrobial peptide bearing a rare S-linked N-acetylglucosamine (GlcNAc) moiety in addition to an O-linked GlcNAc, has been accomplished using a native chemical ligation strategy. 25607533 1 30 theme diglycosylated 118:131 arg1 peptide 147:153 a uniquely diglycosylated antimicrobial peptide 107:153 a uniquely diglycosylated antimicrobial peptide bearing a rare S-linked N-acetylglucosamine (GlcNAc) moiety in addition to an O-linked GlcNAc 107:247 The first total synthesis of glycocin F, a uniquely diglycosylated antimicrobial peptide bearing a rare S-linked N-acetylglucosamine (GlcNAc) moiety in addition to an O-linked GlcNAc, has been accomplished using a native chemical ligation strategy. 25607533 3 31 theme first 534:538 arg1 This 522:525 This 522:525 This 522:525 This is the first comprehensive structural and functional comparison of a naturally occurring glycocin with an active synthetic analogue. 25607533 3 31 theme first 534:538 arg1 comparison 580:589 the first comprehensive structural and functional comparison 530:589 the first comprehensive structural and functional comparison of a naturally occurring glycocin with an active synthetic analogue 530:657 This is the first comprehensive structural and functional comparison of a naturally occurring glycocin with an active synthetic analogue. 25607533 0 32 gly glycopeptide 40:51 arg2 glycopeptide 40:51 the antimicrobial S-linked glycopeptide 13:51 the antimicrobial S-linked glycopeptide 13:51 Synthesis of the antimicrobial S-linked glycopeptide, glycocin F. 25607533 1 33 theme antimicrobial 133:145 arg1 glycocin F 95:104 glycocin F 95:104 glycocin F 95:104 The first total synthesis of glycocin F, a uniquely diglycosylated antimicrobial peptide bearing a rare S-linked N-acetylglucosamine (GlcNAc) moiety in addition to an O-linked GlcNAc, has been accomplished using a native chemical ligation strategy. 25607533 1 33 theme antimicrobial 133:145 arg1 peptide 147:153 a uniquely diglycosylated antimicrobial peptide 107:153 a uniquely diglycosylated antimicrobial peptide bearing a rare S-linked N-acetylglucosamine (GlcNAc) moiety in addition to an O-linked GlcNAc 107:247 The first total synthesis of glycocin F, a uniquely diglycosylated antimicrobial peptide bearing a rare S-linked N-acetylglucosamine (GlcNAc) moiety in addition to an O-linked GlcNAc, has been accomplished using a native chemical ligation strategy. 25607533 2 34 theme mass 385:388 arg1 spectrometry 390:401 mass spectrometry 385:401 mass spectrometry 385:401 The synthetic and naturally occurring peptides were compared by HPLC, mass spectrometry, NMR and CD spectroscopy, and their stability towards chymotrypsin digestion and antimicrobial activity were measured. 25607533 1 35 theme O-linked 233:240 arg1 GlcNAc 242:247 an O-linked GlcNAc 230:247 an O-linked GlcNAc 230:247 The first total synthesis of glycocin F, a uniquely diglycosylated antimicrobial peptide bearing a rare S-linked N-acetylglucosamine (GlcNAc) moiety in addition to an O-linked GlcNAc, has been accomplished using a native chemical ligation strategy. 24928395 5 0 theme Pharmacological 663:677 arg1 inactivation 679:690 Pharmacological inactivation 663:690 Pharmacological inactivation of O-GlcNAcase in preadipocytes 663:722 Pharmacological inactivation of O-GlcNAcase in preadipocytes promoted perinuclear localization of EWS. 24928395 4 1 theme O-linked 586:593 arg1 glycosylation 628:640 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation 586:640 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation of EWS 586:647 Instead, an adipogenesis-dependent increase in O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation of EWS was observed. 24928395 4 2 link O-linked 586:593 arg1 glycosylation 628:640 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation 586:640 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation of EWS 586:647 Instead, an adipogenesis-dependent increase in O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation of EWS was observed. 24928395 3 3 theme EWS 497:499 arg1 signal 487:492 the C-terminal PY-nuclear localization signal 448:492 the C-terminal PY-nuclear localization signal of EWS 448:499 Tyrosine phosphorylation in the C-terminal PY-nuclear localization signal of EWS was negative throughout adipogenesis. 24928395 1 4 theme cell 234:237 arg1 membrane 239:246 the cell membrane 230:246 the cell membrane 230:246 Although the Ewing sarcoma (EWS) proto-oncoprotein is found in the nucleus and cytosol and is associated with the cell membrane, the regulatory mechanisms of its subcellular localization are still unclear. 24928395 0 5 theme O-GlcNAc 80:87 arg1 glycosylation 89:101 its O-GlcNAc glycosylation 76:101 its O-GlcNAc glycosylation in 3T3-L1 cells 76:117 Adipogenesis stimulates the nuclear localization of EWS with an increase in its O-GlcNAc glycosylation in 3T3-L1 cells. 24928395 5 6 theme O-GlcNAcase 695:705 arg1 inactivation 679:690 Pharmacological inactivation 663:690 Pharmacological inactivation of O-GlcNAcase in preadipocytes 663:722 Pharmacological inactivation of O-GlcNAcase in preadipocytes promoted perinuclear localization of EWS. 24928395 4 7 gly glycosylation 628:640 arg1 EWS 645:647 EWS 645:647 EWS 645:647 Instead, an adipogenesis-dependent increase in O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation of EWS was observed. 24928395 4 8 theme β-N-acetylglucosamine 595:615 arg1 glycosylation 628:640 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation 586:640 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation of EWS 586:647 Instead, an adipogenesis-dependent increase in O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation of EWS was observed. 24928395 0 9 theme 3T3-L1 106:111 arg1 cells 113:117 3T3-L1 cells 106:117 3T3-L1 cells 106:117 Adipogenesis stimulates the nuclear localization of EWS with an increase in its O-GlcNAc glycosylation in 3T3-L1 cells. 24928395 4 10 from increase 574:581 arg1 glycosylation 628:640 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation 586:640 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation of EWS 586:647 Instead, an adipogenesis-dependent increase in O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation of EWS was observed. 24928395 0 11 gly glycosylation 89:101 arg1 cells 113:117 3T3-L1 cells 106:117 3T3-L1 cells 106:117 Adipogenesis stimulates the nuclear localization of EWS with an increase in its O-GlcNAc glycosylation in 3T3-L1 cells. 24928395 2 12 theme adipogenic 345:354 arg1 stimuli 356:362 adipogenic stimuli 345:362 adipogenic stimuli 345:362 Here we found that adipogenic stimuli induce the nuclear localization of EWS in 3T3-L1 cells. 24928395 2 13 theme 3T3-L1 406:411 arg1 cells 413:417 3T3-L1 cells 406:417 3T3-L1 cells 406:417 Here we found that adipogenic stimuli induce the nuclear localization of EWS in 3T3-L1 cells. 24928395 6 14 theme EWS 820:822 arg1 localization 804:815 the nuclear localization 792:815 the nuclear localization of EWS 792:822 Our findings suggest that the nuclear localization of EWS is partly regulated by the glycosylation. 24928395 2 15 theme EWS 399:401 arg1 localization 383:394 the nuclear localization 371:394 the nuclear localization of EWS in 3T3-L1 cells 371:417 Here we found that adipogenic stimuli induce the nuclear localization of EWS in 3T3-L1 cells. 24928395 1 16 theme regulatory 253:262 arg1 unclear 317:323 unclear 317:323 unclear 317:323 Although the Ewing sarcoma (EWS) proto-oncoprotein is found in the nucleus and cytosol and is associated with the cell membrane, the regulatory mechanisms of its subcellular localization are still unclear. 24928395 1 16 theme regulatory 253:262 arg1 mechanisms 264:273 the regulatory mechanisms 249:273 the regulatory mechanisms of its subcellular localization 249:305 Although the Ewing sarcoma (EWS) proto-oncoprotein is found in the nucleus and cytosol and is associated with the cell membrane, the regulatory mechanisms of its subcellular localization are still unclear. 24928395 4 17 theme EWS 645:647 arg1 glycosylation 628:640 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation 586:640 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation of EWS 586:647 Instead, an adipogenesis-dependent increase in O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation of EWS was observed. 24928395 4 18 theme adipogenesis-dependent 551:572 arg1 increase 574:581 an adipogenesis-dependent increase 548:581 an adipogenesis-dependent increase in O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation of EWS 548:647 Instead, an adipogenesis-dependent increase in O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation of EWS was observed. 24928395 5 19 theme EWS 761:763 arg1 localization 745:756 perinuclear localization 733:756 perinuclear localization of EWS 733:763 Pharmacological inactivation of O-GlcNAcase in preadipocytes promoted perinuclear localization of EWS. 24928395 3 20 theme Tyrosine 420:427 arg1 phosphorylation 429:443 Tyrosine phosphorylation 420:443 Tyrosine phosphorylation in the C-terminal PY-nuclear localization signal of EWS 420:499 Tyrosine phosphorylation in the C-terminal PY-nuclear localization signal of EWS was negative throughout adipogenesis. 24928395 5 21 from inactivation 679:690 arg1 preadipocytes 710:722 preadipocytes 710:722 preadipocytes 710:722 Pharmacological inactivation of O-GlcNAcase in preadipocytes promoted perinuclear localization of EWS. 24928395 1 22 located found 174:178 arg1 cytosol 199:205 cytosol 199:205 cytosol 199:205 Although the Ewing sarcoma (EWS) proto-oncoprotein is found in the nucleus and cytosol and is associated with the cell membrane, the regulatory mechanisms of its subcellular localization are still unclear. 24928395 1 22 located found 174:178 arg1 nucleus 187:193 nucleus 187:193 nucleus 187:193 Although the Ewing sarcoma (EWS) proto-oncoprotein is found in the nucleus and cytosol and is associated with the cell membrane, the regulatory mechanisms of its subcellular localization are still unclear. 24928395 1 22 located found 174:178 arg2 proto-oncoprotein 153:169 the Ewing sarcoma (EWS) proto-oncoprotein 129:169 the Ewing sarcoma (EWS) proto-oncoprotein 129:169 Although the Ewing sarcoma (EWS) proto-oncoprotein is found in the nucleus and cytosol and is associated with the cell membrane, the regulatory mechanisms of its subcellular localization are still unclear. 24928395 0 23 theme nuclear 28:34 arg1 localization 36:47 the nuclear localization 24:47 the nuclear localization of EWS 24:54 Adipogenesis stimulates the nuclear localization of EWS with an increase in its O-GlcNAc glycosylation in 3T3-L1 cells. 24928395 2 24 theme nuclear 375:381 arg1 localization 383:394 the nuclear localization 371:394 the nuclear localization of EWS in 3T3-L1 cells 371:417 Here we found that adipogenic stimuli induce the nuclear localization of EWS in 3T3-L1 cells. 24928395 3 25 from phosphorylation 429:443 arg1 signal 487:492 the C-terminal PY-nuclear localization signal 448:492 the C-terminal PY-nuclear localization signal of EWS 448:499 Tyrosine phosphorylation in the C-terminal PY-nuclear localization signal of EWS was negative throughout adipogenesis. 24928395 3 26 theme localization 474:485 arg1 signal 487:492 the C-terminal PY-nuclear localization signal 448:492 the C-terminal PY-nuclear localization signal of EWS 448:499 Tyrosine phosphorylation in the C-terminal PY-nuclear localization signal of EWS was negative throughout adipogenesis. 24928395 0 27 theme EWS 52:54 arg1 localization 36:47 the nuclear localization 24:47 the nuclear localization of EWS 24:54 Adipogenesis stimulates the nuclear localization of EWS with an increase in its O-GlcNAc glycosylation in 3T3-L1 cells. 24928395 1 28 theme subcellular 282:292 arg1 localization 294:305 its subcellular localization 278:305 its subcellular localization 278:305 Although the Ewing sarcoma (EWS) proto-oncoprotein is found in the nucleus and cytosol and is associated with the cell membrane, the regulatory mechanisms of its subcellular localization are still unclear. 24928395 6 29 theme nuclear 796:802 arg1 localization 804:815 the nuclear localization 792:815 the nuclear localization of EWS 792:822 Our findings suggest that the nuclear localization of EWS is partly regulated by the glycosylation. 24928395 0 30 from increase 64:71 arg1 glycosylation 89:101 its O-GlcNAc glycosylation 76:101 its O-GlcNAc glycosylation in 3T3-L1 cells 76:117 Adipogenesis stimulates the nuclear localization of EWS with an increase in its O-GlcNAc glycosylation in 3T3-L1 cells. 24928395 1 31 theme localization 294:305 arg1 unclear 317:323 unclear 317:323 unclear 317:323 Although the Ewing sarcoma (EWS) proto-oncoprotein is found in the nucleus and cytosol and is associated with the cell membrane, the regulatory mechanisms of its subcellular localization are still unclear. 24928395 1 31 theme localization 294:305 arg1 mechanisms 264:273 the regulatory mechanisms 249:273 the regulatory mechanisms of its subcellular localization 249:305 Although the Ewing sarcoma (EWS) proto-oncoprotein is found in the nucleus and cytosol and is associated with the cell membrane, the regulatory mechanisms of its subcellular localization are still unclear. 24928395 1 32 dep nucleus 187:193 arg1 the 183:185 the 183:185 the 183:185 Although the Ewing sarcoma (EWS) proto-oncoprotein is found in the nucleus and cytosol and is associated with the cell membrane, the regulatory mechanisms of its subcellular localization are still unclear. 24928395 3 33 theme C-terminal 452:461 arg1 signal 487:492 the C-terminal PY-nuclear localization signal 448:492 the C-terminal PY-nuclear localization signal of EWS 448:499 Tyrosine phosphorylation in the C-terminal PY-nuclear localization signal of EWS was negative throughout adipogenesis. 24928395 5 34 theme perinuclear 733:743 arg1 localization 745:756 perinuclear localization 733:756 perinuclear localization of EWS 733:763 Pharmacological inactivation of O-GlcNAcase in preadipocytes promoted perinuclear localization of EWS. 24928395 0 35 from glycosylation 89:101 arg1 cells 113:117 3T3-L1 cells 106:117 3T3-L1 cells 106:117 Adipogenesis stimulates the nuclear localization of EWS with an increase in its O-GlcNAc glycosylation in 3T3-L1 cells. 24928395 2 36 from localization 383:394 arg1 cells 413:417 3T3-L1 cells 406:417 3T3-L1 cells 406:417 Here we found that adipogenic stimuli induce the nuclear localization of EWS in 3T3-L1 cells. 24928395 3 37 theme PY-nuclear 463:472 arg1 signal 487:492 the C-terminal PY-nuclear localization signal 448:492 the C-terminal PY-nuclear localization signal of EWS 448:499 Tyrosine phosphorylation in the C-terminal PY-nuclear localization signal of EWS was negative throughout adipogenesis. 24928395 1 38 theme Ewing 133:137 arg1 sarcoma 139:145 Ewing sarcoma 133:145 the Ewing sarcoma (EWS) proto-oncoprotein 129:169 Although the Ewing sarcoma (EWS) proto-oncoprotein is found in the nucleus and cytosol and is associated with the cell membrane, the regulatory mechanisms of its subcellular localization are still unclear. 24928395 1 38 theme Ewing 133:137 arg1 EWS 148:150 EWS 148:150 EWS 148:150 Although the Ewing sarcoma (EWS) proto-oncoprotein is found in the nucleus and cytosol and is associated with the cell membrane, the regulatory mechanisms of its subcellular localization are still unclear. 24928395 1 39 theme sarcoma 139:145 arg1 proto-oncoprotein 153:169 the Ewing sarcoma (EWS) proto-oncoprotein 129:169 the Ewing sarcoma (EWS) proto-oncoprotein 129:169 Although the Ewing sarcoma (EWS) proto-oncoprotein is found in the nucleus and cytosol and is associated with the cell membrane, the regulatory mechanisms of its subcellular localization are still unclear. 28573276 0 0 theme promising 81:89 arg1 mechanism 9:17 Reaction mechanism 0:17 Reaction mechanism of the metallohydrolase CpsB from Streptococcus pneumoniae 0:76 Reaction mechanism of the metallohydrolase CpsB from Streptococcus pneumoniae, a promising target for novel antimicrobial agents. 28573276 0 0 theme promising 81:89 arg1 target 91:96 a promising target 79:96 a promising target for novel antimicrobial agents 79:127 Reaction mechanism of the metallohydrolase CpsB from Streptococcus pneumoniae, a promising target for novel antimicrobial agents. 28573276 6 1 theme circular 859:866 arg1 MCD 879:881 MCD 879:881 MCD 879:881 This observation is in agreement with magnetic circular dichroism (MCD) and electron paramagnetic resonance (EPR) data that indicate the presence of two weakly ferromagnetically coupled Co2+ ions in the active site of catalytically active CpsB. 28573276 6 1 theme circular 859:866 arg1 dichroism 868:876 magnetic circular dichroism 850:876 magnetic circular dichroism (MCD) 850:882 This observation is in agreement with magnetic circular dichroism (MCD) and electron paramagnetic resonance (EPR) data that indicate the presence of two weakly ferromagnetically coupled Co2+ ions in the active site of catalytically active CpsB. 28573276 1 2 theme ion-dependent 146:158 arg1 CpsB 130:133 CpsB 130:133 CpsB 130:133 CpsB is a metal ion-dependent hydrolase involved in the biosynthesis of capsular polysaccharides in bacterial organisms. 28573276 1 2 theme ion-dependent 146:158 arg1 hydrolase 160:168 a metal ion-dependent hydrolase 138:168 a metal ion-dependent hydrolase involved in the biosynthesis of capsular polysaccharides in bacterial organisms 138:248 CpsB is a metal ion-dependent hydrolase involved in the biosynthesis of capsular polysaccharides in bacterial organisms. 28573276 5 3 theme crystal 739:745 arg1 structure 747:755 the crystal structure 735:755 the crystal structure 735:755 Using isothermal titration calorimetry (ITC) we have demonstrated that, in contrast to the crystal structure, only two Mn2+ or Co2+ ions bind to a monomer of CpsB. 28573276 0 4 from mechanism 9:17 arg1 pneumoniae 67:76 Streptococcus pneumoniae 53:76 Streptococcus pneumoniae 53:76 Reaction mechanism of the metallohydrolase CpsB from Streptococcus pneumoniae, a promising target for novel antimicrobial agents. 28573276 6 5 theme active 1015:1020 arg1 CpsB 1051:1054 catalytically active CpsB 1030:1054 catalytically active CpsB 1030:1054 This observation is in agreement with magnetic circular dichroism (MCD) and electron paramagnetic resonance (EPR) data that indicate the presence of two weakly ferromagnetically coupled Co2+ ions in the active site of catalytically active CpsB. 28573276 6 5 theme active 1015:1020 arg1 site 1022:1025 the active site 1011:1025 the active site of catalytically active CpsB 1011:1054 This observation is in agreement with magnetic circular dichroism (MCD) and electron paramagnetic resonance (EPR) data that indicate the presence of two weakly ferromagnetically coupled Co2+ ions in the active site of catalytically active CpsB. 28573276 9 6 theme novel 1494:1498 arg1 CpsB 1484:1487 CpsB 1484:1487 CpsB 1484:1487 Thus, the combined physicochemical studies demonstrate that CpsB is a novel member of the dinuclear metallohydrolase family. 28573276 9 6 theme novel 1494:1498 arg1 member 1500:1505 a novel member 1492:1505 a novel member of the dinuclear metallohydrolase family 1492:1546 Thus, the combined physicochemical studies demonstrate that CpsB is a novel member of the dinuclear metallohydrolase family. 28573276 9 7 theme dinuclear 1514:1522 arg1 family 1541:1546 the dinuclear metallohydrolase family 1510:1546 the dinuclear metallohydrolase family 1510:1546 Thus, the combined physicochemical studies demonstrate that CpsB is a novel member of the dinuclear metallohydrolase family. 28573276 6 8 from presence 949:956 arg1 CpsB 1051:1054 catalytically active CpsB 1030:1054 catalytically active CpsB 1030:1054 This observation is in agreement with magnetic circular dichroism (MCD) and electron paramagnetic resonance (EPR) data that indicate the presence of two weakly ferromagnetically coupled Co2+ ions in the active site of catalytically active CpsB. 28573276 6 8 from presence 949:956 arg1 site 1022:1025 the active site 1011:1025 the active site of catalytically active CpsB 1011:1054 This observation is in agreement with magnetic circular dichroism (MCD) and electron paramagnetic resonance (EPR) data that indicate the presence of two weakly ferromagnetically coupled Co2+ ions in the active site of catalytically active CpsB. 28573276 2 9 theme promising 285:293 arg1 target 295:300 a promising target 283:300 a promising target for novel chemotherapeutics to combat antibiotic resistance 283:360 The enzyme has been proposed as a promising target for novel chemotherapeutics to combat antibiotic resistance. 28573276 2 9 theme promising 285:293 arg1 enzyme 255:260 The enzyme 251:260 The enzyme 251:260 The enzyme has been proposed as a promising target for novel chemotherapeutics to combat antibiotic resistance. 28573276 6 10 theme active 1044:1049 arg1 CpsB 1051:1054 catalytically active CpsB 1030:1054 catalytically active CpsB 1030:1054 This observation is in agreement with magnetic circular dichroism (MCD) and electron paramagnetic resonance (EPR) data that indicate the presence of two weakly ferromagnetically coupled Co2+ ions in the active site of catalytically active CpsB. 28573276 0 11 theme antimicrobial 108:120 arg1 agents 122:127 novel antimicrobial agents 102:127 novel antimicrobial agents 102:127 Reaction mechanism of the metallohydrolase CpsB from Streptococcus pneumoniae, a promising target for novel antimicrobial agents. 28573276 9 12 theme combined 1434:1441 arg1 studies 1459:1465 the combined physicochemical studies 1430:1465 the combined physicochemical studies 1430:1465 Thus, the combined physicochemical studies demonstrate that CpsB is a novel member of the dinuclear metallohydrolase family. 28573276 3 13 theme spaced 444:449 arg1 ions 457:460 three closely spaced metal ions 430:460 three closely spaced metal ions 430:460 The crystal structure of CpsB indicated the presence of as many as three closely spaced metal ions, modelled as Mn2+, in the active site. 28573276 0 14 theme novel 102:106 arg1 agents 122:127 novel antimicrobial agents 102:127 novel antimicrobial agents 102:127 Reaction mechanism of the metallohydrolase CpsB from Streptococcus pneumoniae, a promising target for novel antimicrobial agents. 28573276 3 15 theme many 422:425 arg1 presence 407:414 the presence 403:414 the presence of as many as three closely spaced metal ions, modelled as Mn2+, in the active site 403:498 The crystal structure of CpsB indicated the presence of as many as three closely spaced metal ions, modelled as Mn2+, in the active site. 28573276 9 16 theme physicochemical 1443:1457 arg1 studies 1459:1465 the combined physicochemical studies 1430:1465 the combined physicochemical studies 1430:1465 Thus, the combined physicochemical studies demonstrate that CpsB is a novel member of the dinuclear metallohydrolase family. 28573276 3 17 theme metal 451:455 arg1 ions 457:460 three closely spaced metal ions 430:460 three closely spaced metal ions 430:460 The crystal structure of CpsB indicated the presence of as many as three closely spaced metal ions, modelled as Mn2+, in the active site. 28573276 3 18 from presence 407:414 arg1 site 495:498 the active site 484:498 the active site 484:498 The crystal structure of CpsB indicated the presence of as many as three closely spaced metal ions, modelled as Mn2+, in the active site. 28573276 5 19 dep structure 747:755 arg1 contrast 723:730 contrast 723:730 contrast 723:730 Using isothermal titration calorimetry (ITC) we have demonstrated that, in contrast to the crystal structure, only two Mn2+ or Co2+ ions bind to a monomer of CpsB. 28573276 6 20 attach presence 949:956 arg1 CpsB 1051:1054 catalytically active CpsB 1030:1054 catalytically active CpsB 1030:1054 This observation is in agreement with magnetic circular dichroism (MCD) and electron paramagnetic resonance (EPR) data that indicate the presence of two weakly ferromagnetically coupled Co2+ ions in the active site of catalytically active CpsB. 28573276 6 20 attach presence 949:956 arg2 ions 1003:1006 two weakly ferromagnetically coupled Co2+ ions 961:1006 two weakly ferromagnetically coupled Co2+ ions 961:1006 This observation is in agreement with magnetic circular dichroism (MCD) and electron paramagnetic resonance (EPR) data that indicate the presence of two weakly ferromagnetically coupled Co2+ ions in the active site of catalytically active CpsB. 28573276 6 20 attach presence 949:956 arg1 site 1022:1025 the active site 1011:1025 the active site of catalytically active CpsB 1011:1054 This observation is in agreement with magnetic circular dichroism (MCD) and electron paramagnetic resonance (EPR) data that indicate the presence of two weakly ferromagnetically coupled Co2+ ions in the active site of catalytically active CpsB. 28573276 6 21 theme ions 1003:1006 arg1 presence 949:956 the presence 945:956 the presence of two weakly ferromagnetically coupled Co2+ ions in the active site of catalytically active CpsB 945:1054 This observation is in agreement with magnetic circular dichroism (MCD) and electron paramagnetic resonance (EPR) data that indicate the presence of two weakly ferromagnetically coupled Co2+ ions in the active site of catalytically active CpsB. 28573276 0 22 theme Reaction 0:7 arg1 mechanism 9:17 Reaction mechanism 0:17 Reaction mechanism of the metallohydrolase CpsB from Streptococcus pneumoniae 0:76 Reaction mechanism of the metallohydrolase CpsB from Streptococcus pneumoniae, a promising target for novel antimicrobial agents. 28573276 0 22 theme Reaction 0:7 arg1 target 91:96 a promising target 79:96 a promising target for novel antimicrobial agents 79:127 Reaction mechanism of the metallohydrolase CpsB from Streptococcus pneumoniae, a promising target for novel antimicrobial agents. 28573276 9 23 theme family 1541:1546 arg1 CpsB 1484:1487 CpsB 1484:1487 CpsB 1484:1487 Thus, the combined physicochemical studies demonstrate that CpsB is a novel member of the dinuclear metallohydrolase family. 28573276 9 23 theme family 1541:1546 arg1 member 1500:1505 a novel member 1492:1505 a novel member of the dinuclear metallohydrolase family 1492:1546 Thus, the combined physicochemical studies demonstrate that CpsB is a novel member of the dinuclear metallohydrolase family. 28573276 9 24 theme metallohydrolase 1524:1539 arg1 family 1541:1546 the dinuclear metallohydrolase family 1510:1546 the dinuclear metallohydrolase family 1510:1546 Thus, the combined physicochemical studies demonstrate that CpsB is a novel member of the dinuclear metallohydrolase family. 28573276 6 25 theme Co2+ 998:1001 arg1 ions 1003:1006 two weakly ferromagnetically coupled Co2+ ions 961:1006 two weakly ferromagnetically coupled Co2+ ions 961:1006 This observation is in agreement with magnetic circular dichroism (MCD) and electron paramagnetic resonance (EPR) data that indicate the presence of two weakly ferromagnetically coupled Co2+ ions in the active site of catalytically active CpsB. 28573276 3 26 theme CpsB 388:391 arg1 structure 375:383 The crystal structure 363:383 The crystal structure of CpsB 363:391 The crystal structure of CpsB indicated the presence of as many as three closely spaced metal ions, modelled as Mn2+, in the active site. 28573276 6 27 theme resonance 910:918 arg1 data 926:929 magnetic circular dichroism (MCD) and electron paramagnetic resonance (EPR) data 850:929 magnetic circular dichroism (MCD) and electron paramagnetic resonance (EPR) data that indicate the presence of two weakly ferromagnetically coupled Co2+ ions in the active site of catalytically active CpsB 850:1054 This observation is in agreement with magnetic circular dichroism (MCD) and electron paramagnetic resonance (EPR) data that indicate the presence of two weakly ferromagnetically coupled Co2+ ions in the active site of catalytically active CpsB. 28573276 8 28 theme Steady-state 1219:1230 arg1 measurements 1258:1269 Steady-state and stopped-flow kinetics measurements 1219:1269 Steady-state and stopped-flow kinetics measurements 1219:1269 Steady-state and stopped-flow kinetics measurements further indicated that phosphoesters and nitrocefin undergo catalysis in a conserved manner with a metal ion-bridging hydroxide acting as a nucleophile. 28573276 2 29 theme novel 306:310 arg1 chemotherapeutics 312:328 novel chemotherapeutics 306:328 novel chemotherapeutics to combat antibiotic resistance 306:360 The enzyme has been proposed as a promising target for novel chemotherapeutics to combat antibiotic resistance. 28573276 6 30 theme coupled 990:996 arg1 ions 1003:1006 two weakly ferromagnetically coupled Co2+ ions 961:1006 two weakly ferromagnetically coupled Co2+ ions 961:1006 This observation is in agreement with magnetic circular dichroism (MCD) and electron paramagnetic resonance (EPR) data that indicate the presence of two weakly ferromagnetically coupled Co2+ ions in the active site of catalytically active CpsB. 28573276 6 31 theme paramagnetic 897:908 arg1 EPR 921:923 EPR 921:923 EPR 921:923 This observation is in agreement with magnetic circular dichroism (MCD) and electron paramagnetic resonance (EPR) data that indicate the presence of two weakly ferromagnetically coupled Co2+ ions in the active site of catalytically active CpsB. 28573276 6 31 theme paramagnetic 897:908 arg1 resonance 910:918 electron paramagnetic resonance 888:918 electron paramagnetic resonance (EPR) 888:924 This observation is in agreement with magnetic circular dichroism (MCD) and electron paramagnetic resonance (EPR) data that indicate the presence of two weakly ferromagnetically coupled Co2+ ions in the active site of catalytically active CpsB. 28573276 1 32 theme capsular 202:209 arg1 polysaccharides 211:225 capsular polysaccharides 202:225 capsular polysaccharides 202:225 CpsB is a metal ion-dependent hydrolase involved in the biosynthesis of capsular polysaccharides in bacterial organisms. 28573276 0 33 theme CpsB 43:46 arg1 mechanism 9:17 Reaction mechanism 0:17 Reaction mechanism of the metallohydrolase CpsB from Streptococcus pneumoniae 0:76 Reaction mechanism of the metallohydrolase CpsB from Streptococcus pneumoniae, a promising target for novel antimicrobial agents. 28573276 0 33 theme CpsB 43:46 arg1 target 91:96 a promising target 79:96 a promising target for novel antimicrobial agents 79:127 Reaction mechanism of the metallohydrolase CpsB from Streptococcus pneumoniae, a promising target for novel antimicrobial agents. 28573276 6 34 theme electron 888:895 arg1 EPR 921:923 EPR 921:923 EPR 921:923 This observation is in agreement with magnetic circular dichroism (MCD) and electron paramagnetic resonance (EPR) data that indicate the presence of two weakly ferromagnetically coupled Co2+ ions in the active site of catalytically active CpsB. 28573276 6 34 theme electron 888:895 arg1 resonance 910:918 electron paramagnetic resonance 888:918 electron paramagnetic resonance (EPR) 888:924 This observation is in agreement with magnetic circular dichroism (MCD) and electron paramagnetic resonance (EPR) data that indicate the presence of two weakly ferromagnetically coupled Co2+ ions in the active site of catalytically active CpsB. 28573276 8 35 theme conserved 1346:1354 arg1 manner 1356:1361 a conserved manner 1344:1361 a conserved manner with a metal ion-bridging hydroxide acting as a nucleophile 1344:1421 Steady-state and stopped-flow kinetics measurements further indicated that phosphoesters and nitrocefin undergo catalysis in a conserved manner with a metal ion-bridging hydroxide acting as a nucleophile. 28573276 1 36 theme polysaccharides 211:225 arg1 biosynthesis 186:197 the biosynthesis 182:197 the biosynthesis of capsular polysaccharides in bacterial organisms 182:248 CpsB is a metal ion-dependent hydrolase involved in the biosynthesis of capsular polysaccharides in bacterial organisms. 28573276 0 37 theme metallohydrolase 26:41 arg1 CpsB 43:46 the metallohydrolase CpsB 22:46 the metallohydrolase CpsB from Streptococcus pneumoniae 22:76 Reaction mechanism of the metallohydrolase CpsB from Streptococcus pneumoniae, a promising target for novel antimicrobial agents. 28573276 4 38 theme preferred 511:519 arg1 obscure 554:560 obscure 554:560 obscure 554:560 While the preferred metal ion composition in vivo is obscure Mn2+ and Co2+ have been demonstrated to be most effective in reconstituting activity. 28573276 4 38 theme preferred 511:519 arg1 composition 531:541 the preferred metal ion composition 507:541 the preferred metal ion composition in vivo 507:549 While the preferred metal ion composition in vivo is obscure Mn2+ and Co2+ have been demonstrated to be most effective in reconstituting activity. 28573276 8 39 theme stopped-flow 1236:1247 arg1 measurements 1258:1269 Steady-state and stopped-flow kinetics measurements 1219:1269 Steady-state and stopped-flow kinetics measurements 1219:1269 Steady-state and stopped-flow kinetics measurements further indicated that phosphoesters and nitrocefin undergo catalysis in a conserved manner with a metal ion-bridging hydroxide acting as a nucleophile. 28573276 5 40 theme Co2+ 775:778 arg1 ions 780:783 only two Mn2+ or Co2+ ions 758:783 ions 780:783 Using isothermal titration calorimetry (ITC) we have demonstrated that, in contrast to the crystal structure, only two Mn2+ or Co2+ ions bind to a monomer of CpsB. 28573276 3 41 theme crystal 367:373 arg1 structure 375:383 The crystal structure 363:383 The crystal structure of CpsB 363:391 The crystal structure of CpsB indicated the presence of as many as three closely spaced metal ions, modelled as Mn2+, in the active site. 28573276 0 42 theme Streptococcus 53:65 arg1 pneumoniae 67:76 Streptococcus pneumoniae 53:76 Streptococcus pneumoniae 53:76 Reaction mechanism of the metallohydrolase CpsB from Streptococcus pneumoniae, a promising target for novel antimicrobial agents. 28573276 3 43 theme active 488:493 arg1 site 495:498 the active site 484:498 the active site 484:498 The crystal structure of CpsB indicated the presence of as many as three closely spaced metal ions, modelled as Mn2+, in the active site. 28573276 5 44 theme isothermal 654:663 arg1 calorimetry 675:685 isothermal titration calorimetry 654:685 isothermal titration calorimetry (ITC) 654:691 Using isothermal titration calorimetry (ITC) we have demonstrated that, in contrast to the crystal structure, only two Mn2+ or Co2+ ions bind to a monomer of CpsB. 28573276 5 44 theme isothermal 654:663 arg1 ITC 688:690 ITC 688:690 ITC 688:690 Using isothermal titration calorimetry (ITC) we have demonstrated that, in contrast to the crystal structure, only two Mn2+ or Co2+ ions bind to a monomer of CpsB. 28573276 0 45 from pneumoniae 67:76 arg1 CpsB 43:46 the metallohydrolase CpsB 22:46 the metallohydrolase CpsB from Streptococcus pneumoniae 22:76 Reaction mechanism of the metallohydrolase CpsB from Streptococcus pneumoniae, a promising target for novel antimicrobial agents. 28573276 0 45 from pneumoniae 67:76 arg1 mechanism 9:17 Reaction mechanism 0:17 Reaction mechanism of the metallohydrolase CpsB from Streptococcus pneumoniae 0:76 Reaction mechanism of the metallohydrolase CpsB from Streptococcus pneumoniae, a promising target for novel antimicrobial agents. 28573276 0 45 from pneumoniae 67:76 arg1 target 91:96 a promising target 79:96 a promising target for novel antimicrobial agents 79:127 Reaction mechanism of the metallohydrolase CpsB from Streptococcus pneumoniae, a promising target for novel antimicrobial agents. 28573276 8 46 with manner 1356:1361 arg1 hydroxide 1389:1397 a metal ion-bridging hydroxide 1368:1397 a metal ion-bridging hydroxide acting as a nucleophile 1368:1421 Steady-state and stopped-flow kinetics measurements further indicated that phosphoesters and nitrocefin undergo catalysis in a conserved manner with a metal ion-bridging hydroxide acting as a nucleophile. 28573276 7 47 theme β-lactam 1188:1195 arg1 nitrocefin 1207:1216 the β-lactam substrate nitrocefin 1184:1216 the β-lactam substrate nitrocefin 1184:1216 While CpsB is known to be a phosphoesterase we have also been able to demonstrate that this enzyme is efficient in hydrolyzing the β-lactam substrate nitrocefin. 28573276 4 48 theme ion 527:529 arg1 obscure 554:560 obscure 554:560 obscure 554:560 While the preferred metal ion composition in vivo is obscure Mn2+ and Co2+ have been demonstrated to be most effective in reconstituting activity. 28573276 4 48 theme ion 527:529 arg1 composition 531:541 the preferred metal ion composition 507:541 the preferred metal ion composition in vivo 507:549 While the preferred metal ion composition in vivo is obscure Mn2+ and Co2+ have been demonstrated to be most effective in reconstituting activity. 28573276 5 49 theme titration 665:673 arg1 calorimetry 675:685 isothermal titration calorimetry 654:685 isothermal titration calorimetry (ITC) 654:691 Using isothermal titration calorimetry (ITC) we have demonstrated that, in contrast to the crystal structure, only two Mn2+ or Co2+ ions bind to a monomer of CpsB. 28573276 5 49 theme titration 665:673 arg1 ITC 688:690 ITC 688:690 ITC 688:690 Using isothermal titration calorimetry (ITC) we have demonstrated that, in contrast to the crystal structure, only two Mn2+ or Co2+ ions bind to a monomer of CpsB. 28573276 3 50 attach presence 407:414 arg1 site 495:498 the active site 484:498 the active site 484:498 The crystal structure of CpsB indicated the presence of as many as three closely spaced metal ions, modelled as Mn2+, in the active site. 28573276 3 50 attach presence 407:414 arg2 many 422:425 many 422:425 many 422:425 The crystal structure of CpsB indicated the presence of as many as three closely spaced metal ions, modelled as Mn2+, in the active site. 28573276 7 51 theme substrate 1197:1205 arg1 nitrocefin 1207:1216 the β-lactam substrate nitrocefin 1184:1216 the β-lactam substrate nitrocefin 1184:1216 While CpsB is known to be a phosphoesterase we have also been able to demonstrate that this enzyme is efficient in hydrolyzing the β-lactam substrate nitrocefin. 28573276 4 52 theme metal 521:525 arg1 obscure 554:560 obscure 554:560 obscure 554:560 While the preferred metal ion composition in vivo is obscure Mn2+ and Co2+ have been demonstrated to be most effective in reconstituting activity. 28573276 4 52 theme metal 521:525 arg1 composition 531:541 the preferred metal ion composition 507:541 the preferred metal ion composition in vivo 507:549 While the preferred metal ion composition in vivo is obscure Mn2+ and Co2+ have been demonstrated to be most effective in reconstituting activity. 28573276 5 53 dep demonstrated 701:712 arg1 Using 648:652 Using 648:652 Using isothermal titration calorimetry (ITC) 648:691 Using isothermal titration calorimetry (ITC) we have demonstrated that, in contrast to the crystal structure, only two Mn2+ or Co2+ ions bind to a monomer of CpsB. 28573276 8 54 theme metal 1370:1374 arg1 hydroxide 1389:1397 a metal ion-bridging hydroxide 1368:1397 a metal ion-bridging hydroxide acting as a nucleophile 1368:1421 Steady-state and stopped-flow kinetics measurements further indicated that phosphoesters and nitrocefin undergo catalysis in a conserved manner with a metal ion-bridging hydroxide acting as a nucleophile. 28573276 2 55 theme antibiotic 340:349 arg1 resistance 351:360 combat antibiotic resistance 333:360 combat antibiotic resistance 333:360 The enzyme has been proposed as a promising target for novel chemotherapeutics to combat antibiotic resistance. 28573276 6 56 theme magnetic 850:857 arg1 MCD 879:881 MCD 879:881 MCD 879:881 This observation is in agreement with magnetic circular dichroism (MCD) and electron paramagnetic resonance (EPR) data that indicate the presence of two weakly ferromagnetically coupled Co2+ ions in the active site of catalytically active CpsB. 28573276 6 56 theme magnetic 850:857 arg1 dichroism 868:876 magnetic circular dichroism 850:876 magnetic circular dichroism (MCD) 850:882 This observation is in agreement with magnetic circular dichroism (MCD) and electron paramagnetic resonance (EPR) data that indicate the presence of two weakly ferromagnetically coupled Co2+ ions in the active site of catalytically active CpsB. 28573276 1 57 theme bacterial 230:238 arg1 organisms 240:248 bacterial organisms 230:248 bacterial organisms 230:248 CpsB is a metal ion-dependent hydrolase involved in the biosynthesis of capsular polysaccharides in bacterial organisms. 28573276 6 58 with agreement 835:843 arg1 data 926:929 magnetic circular dichroism (MCD) and electron paramagnetic resonance (EPR) data 850:929 magnetic circular dichroism (MCD) and electron paramagnetic resonance (EPR) data that indicate the presence of two weakly ferromagnetically coupled Co2+ ions in the active site of catalytically active CpsB 850:1054 This observation is in agreement with magnetic circular dichroism (MCD) and electron paramagnetic resonance (EPR) data that indicate the presence of two weakly ferromagnetically coupled Co2+ ions in the active site of catalytically active CpsB. 28573276 2 59 theme combat 333:338 arg1 resistance 351:360 combat antibiotic resistance 333:360 combat antibiotic resistance 333:360 The enzyme has been proposed as a promising target for novel chemotherapeutics to combat antibiotic resistance. 28573276 6 60 theme CpsB 1051:1054 arg1 CpsB 1051:1054 catalytically active CpsB 1030:1054 catalytically active CpsB 1030:1054 This observation is in agreement with magnetic circular dichroism (MCD) and electron paramagnetic resonance (EPR) data that indicate the presence of two weakly ferromagnetically coupled Co2+ ions in the active site of catalytically active CpsB. 28573276 6 60 theme CpsB 1051:1054 arg1 site 1022:1025 the active site 1011:1025 the active site of catalytically active CpsB 1011:1054 This observation is in agreement with magnetic circular dichroism (MCD) and electron paramagnetic resonance (EPR) data that indicate the presence of two weakly ferromagnetically coupled Co2+ ions in the active site of catalytically active CpsB. 28573276 1 61 from biosynthesis 186:197 arg1 organisms 240:248 bacterial organisms 230:248 bacterial organisms 230:248 CpsB is a metal ion-dependent hydrolase involved in the biosynthesis of capsular polysaccharides in bacterial organisms. 28573276 8 62 theme kinetics 1249:1256 arg1 measurements 1258:1269 Steady-state and stopped-flow kinetics measurements 1219:1269 Steady-state and stopped-flow kinetics measurements 1219:1269 Steady-state and stopped-flow kinetics measurements further indicated that phosphoesters and nitrocefin undergo catalysis in a conserved manner with a metal ion-bridging hydroxide acting as a nucleophile. 28573276 5 63 theme CpsB 806:809 arg1 CpsB 806:809 CpsB 806:809 CpsB 806:809 Using isothermal titration calorimetry (ITC) we have demonstrated that, in contrast to the crystal structure, only two Mn2+ or Co2+ ions bind to a monomer of CpsB. 28573276 5 63 theme CpsB 806:809 arg1 monomer 795:801 a monomer 793:801 a monomer of CpsB 793:809 Using isothermal titration calorimetry (ITC) we have demonstrated that, in contrast to the crystal structure, only two Mn2+ or Co2+ ions bind to a monomer of CpsB. 28573276 6 64 theme dichroism 868:876 arg1 data 926:929 magnetic circular dichroism (MCD) and electron paramagnetic resonance (EPR) data 850:929 magnetic circular dichroism (MCD) and electron paramagnetic resonance (EPR) data that indicate the presence of two weakly ferromagnetically coupled Co2+ ions in the active site of catalytically active CpsB 850:1054 This observation is in agreement with magnetic circular dichroism (MCD) and electron paramagnetic resonance (EPR) data that indicate the presence of two weakly ferromagnetically coupled Co2+ ions in the active site of catalytically active CpsB. 28573276 8 65 theme ion-bridging 1376:1387 arg1 hydroxide 1389:1397 a metal ion-bridging hydroxide 1368:1397 a metal ion-bridging hydroxide acting as a nucleophile 1368:1421 Steady-state and stopped-flow kinetics measurements further indicated that phosphoesters and nitrocefin undergo catalysis in a conserved manner with a metal ion-bridging hydroxide acting as a nucleophile. 28573276 1 66 theme metal 140:144 arg1 CpsB 130:133 CpsB 130:133 CpsB 130:133 CpsB is a metal ion-dependent hydrolase involved in the biosynthesis of capsular polysaccharides in bacterial organisms. 28573276 1 66 theme metal 140:144 arg1 hydrolase 160:168 a metal ion-dependent hydrolase 138:168 a metal ion-dependent hydrolase involved in the biosynthesis of capsular polysaccharides in bacterial organisms 138:248 CpsB is a metal ion-dependent hydrolase involved in the biosynthesis of capsular polysaccharides in bacterial organisms. 27403872 5 0 theme matters 776:782 arg1 removal 757:763 removal 757:763 removal of organic matters, nitrogen and phosphorus 757:807 In particular, the metabolic processes involved in removal of organic matters, nitrogen and phosphorus were analyzed. 27403872 0 1 from analyses 21:28 arg1 genes 50:54 EPS biosynthesis genes 33:54 EPS biosynthesis genes 33:54 Comparative genomics analyses on EPS biosynthesis genes required for floc formation of Zoogloea resiniphila and other activated sludge bacteria. 27403872 7 2 theme gene 1128:1131 arg1 cluster 1133:1139 this EPS biosynthesis gene cluster 1106:1139 this EPS biosynthesis gene cluster 1106:1139 One of the two asparagine synthase paralogues, associated with this EPS biosynthesis gene cluster, was required for floc formation in Zoogloea. 27403872 9 3 theme repeated 1644:1651 arg1 processes 1679:1687 repeated AS settling and recycling processes 1644:1687 repeated AS settling and recycling processes 1644:1687 Our results indicate that floc formation of desired AS bacteria, including CAP strains, facilitate their recruitment into AS and gradual enrichment via repeated AS settling and recycling processes. 27403872 3 4 theme Zoogloea 503:510 arg1 physiology 489:498 physiology 489:498 physiology 489:498 However, little is known about the genetics, biochemistry and physiology of Zoogloea and its related bacteria. 27403872 3 4 theme Zoogloea 503:510 arg1 biochemistry 472:483 biochemistry 472:483 biochemistry 472:483 However, little is known about the genetics, biochemistry and physiology of Zoogloea and its related bacteria. 27403872 3 4 theme Zoogloea 503:510 arg1 genetics 462:469 the genetics 458:469 the genetics 458:469 However, little is known about the genetics, biochemistry and physiology of Zoogloea and its related bacteria. 27403872 3 4 theme Zoogloea 503:510 arg1 bacteria 528:535 its related bacteria 516:535 its related bacteria 516:535 However, little is known about the genetics, biochemistry and physiology of Zoogloea and its related bacteria. 27403872 9 5 theme AS 1544:1545 arg1 bacteria 1547:1554 desired AS bacteria 1536:1554 desired AS bacteria 1536:1554 Our results indicate that floc formation of desired AS bacteria, including CAP strains, facilitate their recruitment into AS and gradual enrichment via repeated AS settling and recycling processes. 27403872 9 5 theme AS 1544:1545 arg1 strains 1571:1577 CAP strains 1567:1577 CAP strains 1567:1577 Our results indicate that floc formation of desired AS bacteria, including CAP strains, facilitate their recruitment into AS and gradual enrichment via repeated AS settling and recycling processes. 27403872 7 6 theme paralogues 1078:1087 arg1 One 1043:1045 One 1043:1045 One 1043:1045 One of the two asparagine synthase paralogues, associated with this EPS biosynthesis gene cluster, was required for floc formation in Zoogloea. 27403872 7 6 theme paralogues 1078:1087 arg1 paralogues 1078:1087 the two asparagine synthase paralogues 1050:1087 the two asparagine synthase paralogues 1050:1087 One of the two asparagine synthase paralogues, associated with this EPS biosynthesis gene cluster, was required for floc formation in Zoogloea. 27403872 6 7 theme other 919:923 arg1 proteins 925:932 other proteins 919:932 other proteins 919:932 Furthermore, it is revealed that a large gene cluster, encoding eight glycosyltransferases and other proteins involved in biosynthesis and export of extracellular polysaccharides (EPS), was required for floc formation. 27403872 6 8 theme extracellular 973:985 arg1 EPS 1004:1006 EPS 1004:1006 EPS 1004:1006 Furthermore, it is revealed that a large gene cluster, encoding eight glycosyltransferases and other proteins involved in biosynthesis and export of extracellular polysaccharides (EPS), was required for floc formation. 27403872 6 8 theme extracellular 973:985 arg1 polysaccharides 987:1001 extracellular polysaccharides 973:1001 extracellular polysaccharides (EPS) 973:1007 Furthermore, it is revealed that a large gene cluster, encoding eight glycosyltransferases and other proteins involved in biosynthesis and export of extracellular polysaccharides (EPS), was required for floc formation. 27403872 8 9 theme nitrifying 1369:1378 arg1 bacteria 1409:1416 nitrifying Nitrosopira and Nitrosomonas bacteria 1369:1416 nitrifying Nitrosopira and Nitrosomonas bacteria 1369:1416 Similar EPS biosynthesis gene cluster(s) were identified in the genome of other AS proteobacteria including polyphosphate-accumulating Candidatus Accumulibacter phosphatis (CAP) and nitrifying Nitrosopira and Nitrosomonas bacteria, but the gene composition varies interspecifically and intraspecifically. 27403872 4 10 theme genomic 577:583 arg1 analyses 585:592 the comparative genomic analyses 561:592 the comparative genomic analyses on two Zoogloea resiniphila draft genomes and the closely related proteobacterial species commonly found in AS 561:703 This report deals with the comparative genomic analyses on two Zoogloea resiniphila draft genomes and the closely related proteobacterial species commonly found in AS. 27403872 0 11 theme resiniphila 96:106 arg1 formation 74:82 floc formation 69:82 floc formation of Zoogloea resiniphila and other activated sludge bacteria 69:142 Comparative genomics analyses on EPS biosynthesis genes required for floc formation of Zoogloea resiniphila and other activated sludge bacteria. 27403872 9 12 theme gradual 1621:1627 arg1 enrichment 1629:1638 AS and gradual enrichment 1614:1638 AS and gradual enrichment 1614:1638 Our results indicate that floc formation of desired AS bacteria, including CAP strains, facilitate their recruitment into AS and gradual enrichment via repeated AS settling and recycling processes. 27403872 7 13 theme EPS 1111:1113 arg1 cluster 1133:1139 this EPS biosynthesis gene cluster 1106:1139 this EPS biosynthesis gene cluster 1106:1139 One of the two asparagine synthase paralogues, associated with this EPS biosynthesis gene cluster, was required for floc formation in Zoogloea. 27403872 8 14 theme gene 1427:1430 arg1 composition 1432:1442 the gene composition 1423:1442 the gene composition 1423:1442 Similar EPS biosynthesis gene cluster(s) were identified in the genome of other AS proteobacteria including polyphosphate-accumulating Candidatus Accumulibacter phosphatis (CAP) and nitrifying Nitrosopira and Nitrosomonas bacteria, but the gene composition varies interspecifically and intraspecifically. 27403872 8 15 theme Nitrosomonas 1396:1407 arg1 bacteria 1409:1416 nitrifying Nitrosopira and Nitrosomonas bacteria 1369:1416 nitrifying Nitrosopira and Nitrosomonas bacteria 1369:1416 Similar EPS biosynthesis gene cluster(s) were identified in the genome of other AS proteobacteria including polyphosphate-accumulating Candidatus Accumulibacter phosphatis (CAP) and nitrifying Nitrosopira and Nitrosomonas bacteria, but the gene composition varies interspecifically and intraspecifically. 27403872 0 16 theme Zoogloea 87:94 arg1 resiniphila 96:106 Zoogloea resiniphila 87:106 Zoogloea resiniphila 87:106 Comparative genomics analyses on EPS biosynthesis genes required for floc formation of Zoogloea resiniphila and other activated sludge bacteria. 27403872 4 17 from analyses 585:592 arg1 species 676:682 the closely related proteobacterial species 640:682 the closely related proteobacterial species commonly found in AS 640:703 This report deals with the comparative genomic analyses on two Zoogloea resiniphila draft genomes and the closely related proteobacterial species commonly found in AS. 27403872 4 17 from analyses 585:592 arg1 genomes 628:634 two Zoogloea resiniphila draft genomes 597:634 two Zoogloea resiniphila draft genomes 597:634 This report deals with the comparative genomic analyses on two Zoogloea resiniphila draft genomes and the closely related proteobacterial species commonly found in AS. 27403872 7 18 theme biosynthesis 1115:1126 arg1 cluster 1133:1139 this EPS biosynthesis gene cluster 1106:1139 this EPS biosynthesis gene cluster 1106:1139 One of the two asparagine synthase paralogues, associated with this EPS biosynthesis gene cluster, was required for floc formation in Zoogloea. 27403872 2 19 theme floc-forming 283:294 arg1 bacteria 296:303 its related floc-forming bacteria 271:303 its related floc-forming bacteria 271:303 Zoolgoea and its related floc-forming bacteria are required for formation of AS flocs which is the key to gravitational effluent-and-sludge separation and AS recycling. 27403872 9 20 theme floc 1518:1521 arg1 formation 1523:1531 floc formation 1518:1531 floc formation of desired AS bacteria, including CAP strains, 1518:1578 Our results indicate that floc formation of desired AS bacteria, including CAP strains, facilitate their recruitment into AS and gradual enrichment via repeated AS settling and recycling processes. 27403872 8 21 theme Similar 1187:1193 arg1 EPS 1195:1197 Similar EPS 1187:1197 Similar EPS biosynthesis gene cluster(s) 1187:1226 Similar EPS biosynthesis gene cluster(s) were identified in the genome of other AS proteobacteria including polyphosphate-accumulating Candidatus Accumulibacter phosphatis (CAP) and nitrifying Nitrosopira and Nitrosomonas bacteria, but the gene composition varies interspecifically and intraspecifically. 27403872 0 22 theme other 112:116 arg1 bacteria 135:142 other activated sludge bacteria 112:142 other activated sludge bacteria 112:142 Comparative genomics analyses on EPS biosynthesis genes required for floc formation of Zoogloea resiniphila and other activated sludge bacteria. 27403872 7 23 from formation 1164:1172 arg1 Zoogloea 1177:1184 Zoogloea 1177:1184 Zoogloea 1177:1184 One of the two asparagine synthase paralogues, associated with this EPS biosynthesis gene cluster, was required for floc formation in Zoogloea. 27403872 2 24 theme related 275:281 arg1 bacteria 296:303 its related floc-forming bacteria 271:303 its related floc-forming bacteria 271:303 Zoolgoea and its related floc-forming bacteria are required for formation of AS flocs which is the key to gravitational effluent-and-sludge separation and AS recycling. 27403872 9 25 theme bacteria 1547:1554 arg1 formation 1523:1531 floc formation 1518:1531 floc formation of desired AS bacteria, including CAP strains, 1518:1578 Our results indicate that floc formation of desired AS bacteria, including CAP strains, facilitate their recruitment into AS and gradual enrichment via repeated AS settling and recycling processes. 27403872 6 26 theme floc 1027:1030 arg1 formation 1032:1040 floc formation 1027:1040 floc formation 1027:1040 Furthermore, it is revealed that a large gene cluster, encoding eight glycosyltransferases and other proteins involved in biosynthesis and export of extracellular polysaccharides (EPS), was required for floc formation. 27403872 4 27 theme proteobacterial 660:674 arg1 species 676:682 the closely related proteobacterial species 640:682 the closely related proteobacterial species commonly found in AS 640:703 This report deals with the comparative genomic analyses on two Zoogloea resiniphila draft genomes and the closely related proteobacterial species commonly found in AS. 27403872 0 28 theme genomics 12:19 arg1 analyses 21:28 Comparative genomics analyses 0:28 Comparative genomics analyses on EPS biosynthesis genes 0:54 Comparative genomics analyses on EPS biosynthesis genes required for floc formation of Zoogloea resiniphila and other activated sludge bacteria. 27403872 9 29 theme CAP 1567:1569 arg1 strains 1571:1577 CAP strains 1567:1577 CAP strains 1567:1577 Our results indicate that floc formation of desired AS bacteria, including CAP strains, facilitate their recruitment into AS and gradual enrichment via repeated AS settling and recycling processes. 27403872 8 30 dep EPS 1195:1197 arg1 cluster 1217:1223 biosynthesis gene cluster 1199:1223 Similar EPS biosynthesis gene cluster(s) 1187:1226 Similar EPS biosynthesis gene cluster(s) were identified in the genome of other AS proteobacteria including polyphosphate-accumulating Candidatus Accumulibacter phosphatis (CAP) and nitrifying Nitrosopira and Nitrosomonas bacteria, but the gene composition varies interspecifically and intraspecifically. 27403872 8 30 dep EPS 1195:1197 arg1 s 1225:1225 s 1225:1225 s 1225:1225 Similar EPS biosynthesis gene cluster(s) were identified in the genome of other AS proteobacteria including polyphosphate-accumulating Candidatus Accumulibacter phosphatis (CAP) and nitrifying Nitrosopira and Nitrosomonas bacteria, but the gene composition varies interspecifically and intraspecifically. 27403872 2 31 theme effluent-and-sludge 378:396 arg1 separation 398:407 gravitational effluent-and-sludge separation 364:407 gravitational effluent-and-sludge separation 364:407 Zoolgoea and its related floc-forming bacteria are required for formation of AS flocs which is the key to gravitational effluent-and-sludge separation and AS recycling. 27403872 0 32 theme Comparative 0:10 arg1 analyses 21:28 Comparative genomics analyses 0:28 Comparative genomics analyses on EPS biosynthesis genes 0:54 Comparative genomics analyses on EPS biosynthesis genes required for floc formation of Zoogloea resiniphila and other activated sludge bacteria. 27403872 8 33 theme Nitrosopira 1380:1390 arg1 bacteria 1409:1416 nitrifying Nitrosopira and Nitrosomonas bacteria 1369:1416 nitrifying Nitrosopira and Nitrosomonas bacteria 1369:1416 Similar EPS biosynthesis gene cluster(s) were identified in the genome of other AS proteobacteria including polyphosphate-accumulating Candidatus Accumulibacter phosphatis (CAP) and nitrifying Nitrosopira and Nitrosomonas bacteria, but the gene composition varies interspecifically and intraspecifically. 27403872 2 34 theme gravitational 364:376 arg1 separation 398:407 gravitational effluent-and-sludge separation 364:407 gravitational effluent-and-sludge separation 364:407 Zoolgoea and its related floc-forming bacteria are required for formation of AS flocs which is the key to gravitational effluent-and-sludge separation and AS recycling. 27403872 7 35 theme floc 1159:1162 arg1 formation 1164:1172 floc formation 1159:1172 floc formation in Zoogloea 1159:1184 One of the two asparagine synthase paralogues, associated with this EPS biosynthesis gene cluster, was required for floc formation in Zoogloea. 27403872 6 36 theme polysaccharides 987:1001 arg1 export 963:968 export 963:968 export 963:968 Furthermore, it is revealed that a large gene cluster, encoding eight glycosyltransferases and other proteins involved in biosynthesis and export of extracellular polysaccharides (EPS), was required for floc formation. 27403872 6 36 theme polysaccharides 987:1001 arg1 biosynthesis 946:957 biosynthesis 946:957 biosynthesis 946:957 Furthermore, it is revealed that a large gene cluster, encoding eight glycosyltransferases and other proteins involved in biosynthesis and export of extracellular polysaccharides (EPS), was required for floc formation. 27403872 0 37 theme sludge 128:133 arg1 bacteria 135:142 other activated sludge bacteria 112:142 other activated sludge bacteria 112:142 Comparative genomics analyses on EPS biosynthesis genes required for floc formation of Zoogloea resiniphila and other activated sludge bacteria. 27403872 8 38 theme Candidatus 1322:1331 arg1 CAP 1360:1362 CAP 1360:1362 CAP 1360:1362 Similar EPS biosynthesis gene cluster(s) were identified in the genome of other AS proteobacteria including polyphosphate-accumulating Candidatus Accumulibacter phosphatis (CAP) and nitrifying Nitrosopira and Nitrosomonas bacteria, but the gene composition varies interspecifically and intraspecifically. 27403872 8 38 theme Candidatus 1322:1331 arg1 phosphatis 1348:1357 polyphosphate-accumulating Candidatus Accumulibacter phosphatis 1295:1357 polyphosphate-accumulating Candidatus Accumulibacter phosphatis (CAP) 1295:1363 Similar EPS biosynthesis gene cluster(s) were identified in the genome of other AS proteobacteria including polyphosphate-accumulating Candidatus Accumulibacter phosphatis (CAP) and nitrifying Nitrosopira and Nitrosomonas bacteria, but the gene composition varies interspecifically and intraspecifically. 27403872 9 39 theme AS 1614:1615 arg1 enrichment 1629:1638 AS and gradual enrichment 1614:1638 AS and gradual enrichment 1614:1638 Our results indicate that floc formation of desired AS bacteria, including CAP strains, facilitate their recruitment into AS and gradual enrichment via repeated AS settling and recycling processes. 27403872 4 40 theme comparative 565:575 arg1 analyses 585:592 the comparative genomic analyses 561:592 the comparative genomic analyses on two Zoogloea resiniphila draft genomes and the closely related proteobacterial species commonly found in AS 561:703 This report deals with the comparative genomic analyses on two Zoogloea resiniphila draft genomes and the closely related proteobacterial species commonly found in AS. 27403872 0 41 theme activated 118:126 arg1 bacteria 135:142 other activated sludge bacteria 112:142 other activated sludge bacteria 112:142 Comparative genomics analyses on EPS biosynthesis genes required for floc formation of Zoogloea resiniphila and other activated sludge bacteria. 27403872 1 42 dep sludge 155:160 arg1 AS 163:164 AS 163:164 AS 163:164 Activated sludge (AS) process has been widely utilized for municipal sewage and industrial wastewater treatment. 27403872 8 43 theme Accumulibacter 1333:1346 arg1 CAP 1360:1362 CAP 1360:1362 CAP 1360:1362 Similar EPS biosynthesis gene cluster(s) were identified in the genome of other AS proteobacteria including polyphosphate-accumulating Candidatus Accumulibacter phosphatis (CAP) and nitrifying Nitrosopira and Nitrosomonas bacteria, but the gene composition varies interspecifically and intraspecifically. 27403872 8 43 theme Accumulibacter 1333:1346 arg1 phosphatis 1348:1357 polyphosphate-accumulating Candidatus Accumulibacter phosphatis 1295:1357 polyphosphate-accumulating Candidatus Accumulibacter phosphatis (CAP) 1295:1363 Similar EPS biosynthesis gene cluster(s) were identified in the genome of other AS proteobacteria including polyphosphate-accumulating Candidatus Accumulibacter phosphatis (CAP) and nitrifying Nitrosopira and Nitrosomonas bacteria, but the gene composition varies interspecifically and intraspecifically. 27403872 0 44 theme biosynthesis 37:48 arg1 genes 50:54 EPS biosynthesis genes 33:54 EPS biosynthesis genes 33:54 Comparative genomics analyses on EPS biosynthesis genes required for floc formation of Zoogloea resiniphila and other activated sludge bacteria. 27403872 8 45 theme AS 1267:1268 arg1 proteobacteria 1270:1283 other AS proteobacteria 1261:1283 other AS proteobacteria 1261:1283 Similar EPS biosynthesis gene cluster(s) were identified in the genome of other AS proteobacteria including polyphosphate-accumulating Candidatus Accumulibacter phosphatis (CAP) and nitrifying Nitrosopira and Nitrosomonas bacteria, but the gene composition varies interspecifically and intraspecifically. 27403872 9 46 theme desired 1536:1542 arg1 bacteria 1547:1554 desired AS bacteria 1536:1554 desired AS bacteria 1536:1554 Our results indicate that floc formation of desired AS bacteria, including CAP strains, facilitate their recruitment into AS and gradual enrichment via repeated AS settling and recycling processes. 27403872 9 46 theme desired 1536:1542 arg1 strains 1571:1577 CAP strains 1567:1577 CAP strains 1567:1577 Our results indicate that floc formation of desired AS bacteria, including CAP strains, facilitate their recruitment into AS and gradual enrichment via repeated AS settling and recycling processes. 27403872 6 47 theme gene 865:868 arg1 cluster 870:876 a large gene cluster 857:876 a large gene cluster 857:876 Furthermore, it is revealed that a large gene cluster, encoding eight glycosyltransferases and other proteins involved in biosynthesis and export of extracellular polysaccharides (EPS), was required for floc formation. 27403872 8 48 theme polyphosphate-accumulating 1295:1320 arg1 CAP 1360:1362 CAP 1360:1362 CAP 1360:1362 Similar EPS biosynthesis gene cluster(s) were identified in the genome of other AS proteobacteria including polyphosphate-accumulating Candidatus Accumulibacter phosphatis (CAP) and nitrifying Nitrosopira and Nitrosomonas bacteria, but the gene composition varies interspecifically and intraspecifically. 27403872 8 48 theme polyphosphate-accumulating 1295:1320 arg1 phosphatis 1348:1357 polyphosphate-accumulating Candidatus Accumulibacter phosphatis 1295:1357 polyphosphate-accumulating Candidatus Accumulibacter phosphatis (CAP) 1295:1363 Similar EPS biosynthesis gene cluster(s) were identified in the genome of other AS proteobacteria including polyphosphate-accumulating Candidatus Accumulibacter phosphatis (CAP) and nitrifying Nitrosopira and Nitrosomonas bacteria, but the gene composition varies interspecifically and intraspecifically. 27403872 4 49 theme related 652:658 arg1 species 676:682 the closely related proteobacterial species 640:682 the closely related proteobacterial species commonly found in AS 640:703 This report deals with the comparative genomic analyses on two Zoogloea resiniphila draft genomes and the closely related proteobacterial species commonly found in AS. 27403872 0 50 theme EPS 33:35 arg1 genes 50:54 EPS biosynthesis genes 33:54 EPS biosynthesis genes 33:54 Comparative genomics analyses on EPS biosynthesis genes required for floc formation of Zoogloea resiniphila and other activated sludge bacteria. 27403872 0 51 theme bacteria 135:142 arg1 formation 74:82 floc formation 69:82 floc formation of Zoogloea resiniphila and other activated sludge bacteria 69:142 Comparative genomics analyses on EPS biosynthesis genes required for floc formation of Zoogloea resiniphila and other activated sludge bacteria. 27403872 6 52 theme large 859:863 arg1 cluster 870:876 a large gene cluster 857:876 a large gene cluster 857:876 Furthermore, it is revealed that a large gene cluster, encoding eight glycosyltransferases and other proteins involved in biosynthesis and export of extracellular polysaccharides (EPS), was required for floc formation. 27403872 8 53 theme biosynthesis 1199:1210 arg1 cluster 1217:1223 biosynthesis gene cluster 1199:1223 Similar EPS biosynthesis gene cluster(s) 1187:1226 Similar EPS biosynthesis gene cluster(s) were identified in the genome of other AS proteobacteria including polyphosphate-accumulating Candidatus Accumulibacter phosphatis (CAP) and nitrifying Nitrosopira and Nitrosomonas bacteria, but the gene composition varies interspecifically and intraspecifically. 27403872 8 53 theme biosynthesis 1199:1210 arg1 s 1225:1225 s 1225:1225 s 1225:1225 Similar EPS biosynthesis gene cluster(s) were identified in the genome of other AS proteobacteria including polyphosphate-accumulating Candidatus Accumulibacter phosphatis (CAP) and nitrifying Nitrosopira and Nitrosomonas bacteria, but the gene composition varies interspecifically and intraspecifically. 27403872 1 54 theme municipal 204:212 arg1 treatment 247:255 municipal sewage and industrial wastewater treatment 204:255 municipal sewage and industrial wastewater treatment 204:255 Activated sludge (AS) process has been widely utilized for municipal sewage and industrial wastewater treatment. 27403872 8 55 theme proteobacteria 1270:1283 arg1 genome 1251:1256 the genome 1247:1256 the genome of other AS proteobacteria 1247:1283 Similar EPS biosynthesis gene cluster(s) were identified in the genome of other AS proteobacteria including polyphosphate-accumulating Candidatus Accumulibacter phosphatis (CAP) and nitrifying Nitrosopira and Nitrosomonas bacteria, but the gene composition varies interspecifically and intraspecifically. 27403872 8 56 theme gene 1212:1215 arg1 cluster 1217:1223 biosynthesis gene cluster 1199:1223 Similar EPS biosynthesis gene cluster(s) 1187:1226 Similar EPS biosynthesis gene cluster(s) were identified in the genome of other AS proteobacteria including polyphosphate-accumulating Candidatus Accumulibacter phosphatis (CAP) and nitrifying Nitrosopira and Nitrosomonas bacteria, but the gene composition varies interspecifically and intraspecifically. 27403872 8 56 theme gene 1212:1215 arg1 s 1225:1225 s 1225:1225 s 1225:1225 Similar EPS biosynthesis gene cluster(s) were identified in the genome of other AS proteobacteria including polyphosphate-accumulating Candidatus Accumulibacter phosphatis (CAP) and nitrifying Nitrosopira and Nitrosomonas bacteria, but the gene composition varies interspecifically and intraspecifically. 27403872 4 57 located found 693:697 arg2 species 676:682 the closely related proteobacterial species 640:682 the closely related proteobacterial species commonly found in AS 640:703 This report deals with the comparative genomic analyses on two Zoogloea resiniphila draft genomes and the closely related proteobacterial species commonly found in AS. 27403872 4 57 located found 693:697 arg1 AS 702:703 AS 702:703 AS 702:703 This report deals with the comparative genomic analyses on two Zoogloea resiniphila draft genomes and the closely related proteobacterial species commonly found in AS. 27403872 1 58 used utilized 191:198 arg2 process 167:173 Activated sludge (AS) process 145:173 Activated sludge (AS) process 145:173 Activated sludge (AS) process has been widely utilized for municipal sewage and industrial wastewater treatment. 27403872 7 59 theme asparagine 1058:1067 arg1 paralogues 1078:1087 the two asparagine synthase paralogues 1050:1087 the two asparagine synthase paralogues 1050:1087 One of the two asparagine synthase paralogues, associated with this EPS biosynthesis gene cluster, was required for floc formation in Zoogloea. 27403872 5 60 theme metabolic 725:733 arg1 processes 735:743 the metabolic processes 721:743 the metabolic processes involved in removal of organic matters, nitrogen and phosphorus 721:807 In particular, the metabolic processes involved in removal of organic matters, nitrogen and phosphorus were analyzed. 27403872 7 61 theme synthase 1069:1076 arg1 paralogues 1078:1087 the two asparagine synthase paralogues 1050:1087 the two asparagine synthase paralogues 1050:1087 One of the two asparagine synthase paralogues, associated with this EPS biosynthesis gene cluster, was required for floc formation in Zoogloea. 27403872 2 62 theme flocs 338:342 arg1 key 357:359 key 357:359 key 357:359 Zoolgoea and its related floc-forming bacteria are required for formation of AS flocs which is the key to gravitational effluent-and-sludge separation and AS recycling. 27403872 2 62 theme flocs 338:342 arg1 formation 322:330 formation 322:330 formation of AS flocs which is the key to gravitational effluent-and-sludge separation and AS recycling 322:424 Zoolgoea and its related floc-forming bacteria are required for formation of AS flocs which is the key to gravitational effluent-and-sludge separation and AS recycling. 27403872 8 63 theme other 1261:1265 arg1 proteobacteria 1270:1283 other AS proteobacteria 1261:1283 other AS proteobacteria 1261:1283 Similar EPS biosynthesis gene cluster(s) were identified in the genome of other AS proteobacteria including polyphosphate-accumulating Candidatus Accumulibacter phosphatis (CAP) and nitrifying Nitrosopira and Nitrosomonas bacteria, but the gene composition varies interspecifically and intraspecifically. 27403872 2 64 theme AS 335:336 arg1 flocs 338:342 AS flocs 335:342 AS flocs 335:342 Zoolgoea and its related floc-forming bacteria are required for formation of AS flocs which is the key to gravitational effluent-and-sludge separation and AS recycling. 27403872 1 65 theme sewage 214:219 arg1 treatment 247:255 municipal sewage and industrial wastewater treatment 204:255 municipal sewage and industrial wastewater treatment 204:255 Activated sludge (AS) process has been widely utilized for municipal sewage and industrial wastewater treatment. 27403872 3 66 theme related 520:526 arg1 bacteria 528:535 its related bacteria 516:535 its related bacteria 516:535 However, little is known about the genetics, biochemistry and physiology of Zoogloea and its related bacteria. 27403872 4 67 theme Zoogloea 601:608 arg1 genomes 628:634 two Zoogloea resiniphila draft genomes 597:634 two Zoogloea resiniphila draft genomes 597:634 This report deals with the comparative genomic analyses on two Zoogloea resiniphila draft genomes and the closely related proteobacterial species commonly found in AS. 27403872 0 68 theme floc 69:72 arg1 formation 74:82 floc formation 69:82 floc formation of Zoogloea resiniphila and other activated sludge bacteria 69:142 Comparative genomics analyses on EPS biosynthesis genes required for floc formation of Zoogloea resiniphila and other activated sludge bacteria. 27403872 4 69 dep Zoogloea 601:608 arg1 resiniphila 610:620 resiniphila 610:620 resiniphila 610:620 This report deals with the comparative genomic analyses on two Zoogloea resiniphila draft genomes and the closely related proteobacterial species commonly found in AS. 27403872 9 70 theme recycling 1669:1677 arg1 processes 1679:1687 repeated AS settling and recycling processes 1644:1687 repeated AS settling and recycling processes 1644:1687 Our results indicate that floc formation of desired AS bacteria, including CAP strains, facilitate their recruitment into AS and gradual enrichment via repeated AS settling and recycling processes. 27403872 1 71 theme Activated 145:153 arg1 process 167:173 Activated sludge (AS) process 145:173 Activated sludge (AS) process 145:173 Activated sludge (AS) process has been widely utilized for municipal sewage and industrial wastewater treatment. 27403872 1 72 theme industrial 225:234 arg1 treatment 247:255 municipal sewage and industrial wastewater treatment 204:255 municipal sewage and industrial wastewater treatment 204:255 Activated sludge (AS) process has been widely utilized for municipal sewage and industrial wastewater treatment. 27403872 5 73 theme organic 768:774 arg1 phosphorus 798:807 phosphorus 798:807 phosphorus 798:807 In particular, the metabolic processes involved in removal of organic matters, nitrogen and phosphorus were analyzed. 27403872 5 73 theme organic 768:774 arg1 nitrogen 785:792 nitrogen 785:792 nitrogen 785:792 In particular, the metabolic processes involved in removal of organic matters, nitrogen and phosphorus were analyzed. 27403872 5 73 theme organic 768:774 arg1 matters 776:782 organic matters 768:782 organic matters 768:782 In particular, the metabolic processes involved in removal of organic matters, nitrogen and phosphorus were analyzed. 27403872 4 74 theme draft 622:626 arg1 genomes 628:634 two Zoogloea resiniphila draft genomes 597:634 two Zoogloea resiniphila draft genomes 597:634 This report deals with the comparative genomic analyses on two Zoogloea resiniphila draft genomes and the closely related proteobacterial species commonly found in AS. 27403872 1 75 theme sludge 155:160 arg1 process 167:173 Activated sludge (AS) process 145:173 Activated sludge (AS) process 145:173 Activated sludge (AS) process has been widely utilized for municipal sewage and industrial wastewater treatment. 27403872 1 76 theme wastewater 236:245 arg1 treatment 247:255 municipal sewage and industrial wastewater treatment 204:255 municipal sewage and industrial wastewater treatment 204:255 Activated sludge (AS) process has been widely utilized for municipal sewage and industrial wastewater treatment. 26709080 2 0 theme microalgae 496:505 arg1 species 507:513 several chosen microalgae species 481:513 several chosen microalgae species 481:513 In this study, we studied the antileukemic activity of several chosen microalgae species at the molecular level and assessed their potential for drug development. 26709080 3 1 dep agent 758:762 arg1 potentials 764:773 potentials 764:773 possible antileukemic agent potentials 736:773 Here we identified Stichococcus bacillaris, Phaeodactylum tricornutum, Microcystis aeruginosa and Nannochloropsis oculata microalgae extracts with possible antileukemic agent potentials. 26709080 1 2 from rich 180:183 arg1 minerals 209:216 minerals 209:216 minerals 209:216 Microalgae are very rich in bioactive compounds, minerals, polysaccharides, poly-unsaturated fatty acids and vitamins, and these rich constituents make microalgae an important resource for the discovery of new bioactive compounds with applications in biotechnology. 26709080 1 2 from rich 180:183 arg1 polysaccharides 219:233 polysaccharides 219:233 polysaccharides 219:233 Microalgae are very rich in bioactive compounds, minerals, polysaccharides, poly-unsaturated fatty acids and vitamins, and these rich constituents make microalgae an important resource for the discovery of new bioactive compounds with applications in biotechnology. 26709080 1 2 from rich 180:183 arg1 vitamins 269:276 vitamins 269:276 vitamins 269:276 Microalgae are very rich in bioactive compounds, minerals, polysaccharides, poly-unsaturated fatty acids and vitamins, and these rich constituents make microalgae an important resource for the discovery of new bioactive compounds with applications in biotechnology. 26709080 1 2 from rich 180:183 arg1 acids 259:263 poly-unsaturated fatty acids 236:263 poly-unsaturated fatty acids 236:263 Microalgae are very rich in bioactive compounds, minerals, polysaccharides, poly-unsaturated fatty acids and vitamins, and these rich constituents make microalgae an important resource for the discovery of new bioactive compounds with applications in biotechnology. 26709080 1 2 from rich 180:183 arg1 compounds 198:206 bioactive compounds 188:206 bioactive compounds 188:206 Microalgae are very rich in bioactive compounds, minerals, polysaccharides, poly-unsaturated fatty acids and vitamins, and these rich constituents make microalgae an important resource for the discovery of new bioactive compounds with applications in biotechnology. 26709080 6 3 theme essential 1169:1177 arg1 oils 1179:1182 these essential oils 1163:1182 these essential oils 1163:1182 Finally, to identify potential molecular targets causing the phenotypic changes in leukemic cell lines, we docked a selected group of these essential oils to several key intracellular proteins. 26709080 6 4 theme phenotypic 1090:1099 arg1 changes 1101:1107 the phenotypic changes 1086:1107 the phenotypic changes in leukemic cell lines 1086:1130 Finally, to identify potential molecular targets causing the phenotypic changes in leukemic cell lines, we docked a selected group of these essential oils to several key intracellular proteins. 26709080 0 5 theme extracts 66:73 arg1 modeling 93:100 computational modeling 79:100 computational modeling of their interactions with intracellular signaling nodes 79:157 Screening of new antileukemic agents from essential oils of algae extracts and computational modeling of their interactions with intracellular signaling nodes. 26709080 0 5 theme extracts 66:73 arg1 oils 52:55 essential oils 42:55 essential oils of algae extracts 42:73 Screening of new antileukemic agents from essential oils of algae extracts and computational modeling of their interactions with intracellular signaling nodes. 26709080 3 6 theme possible 736:743 arg1 agent 758:762 possible antileukemic agent 736:762 possible antileukemic agent potentials 736:773 Here we identified Stichococcus bacillaris, Phaeodactylum tricornutum, Microcystis aeruginosa and Nannochloropsis oculata microalgae extracts with possible antileukemic agent potentials. 26709080 3 7 dep bacillaris 621:630 arg1 extracts 722:729 microalgae extracts 711:729 microalgae extracts 711:729 Here we identified Stichococcus bacillaris, Phaeodactylum tricornutum, Microcystis aeruginosa and Nannochloropsis oculata microalgae extracts with possible antileukemic agent potentials. 26709080 5 8 theme gas 983:985 arg1 spectrometry 1007:1018 gas chromatography-mass spectrometry 983:1018 gas chromatography-mass spectrometry (GC-MS) 983:1026 We characterized the composition of essential oils of these fifteen different algae extracts using gas chromatography-mass spectrometry (GC-MS). 26709080 5 8 theme gas 983:985 arg1 GC-MS 1021:1025 GC-MS 1021:1025 GC-MS 1021:1025 We characterized the composition of essential oils of these fifteen different algae extracts using gas chromatography-mass spectrometry (GC-MS). 26709080 3 9 theme antileukemic 745:756 arg1 agent 758:762 possible antileukemic agent 736:762 possible antileukemic agent potentials 736:773 Here we identified Stichococcus bacillaris, Phaeodactylum tricornutum, Microcystis aeruginosa and Nannochloropsis oculata microalgae extracts with possible antileukemic agent potentials. 26709080 7 10 theme essential 1283:1291 arg1 oils 1293:1296 these essential oils 1277:1296 these essential oils analyzed 1277:1305 According to results of rank score algorithm, five of these essential oils analyzed might be considered as in silico plausible candidates to be used as antileukemic agents. 26709080 0 11 theme computational 79:91 arg1 modeling 93:100 computational modeling 79:100 computational modeling of their interactions with intracellular signaling nodes 79:157 Screening of new antileukemic agents from essential oils of algae extracts and computational modeling of their interactions with intracellular signaling nodes. 26709080 0 12 from oils 52:55 arg1 Screening 0:8 Screening 0:8 Screening of new antileukemic agents from essential oils of algae extracts and computational modeling of their interactions with intracellular signaling nodes. 0:158 Screening of new antileukemic agents from essential oils of algae extracts and computational modeling of their interactions with intracellular signaling nodes. 26709080 4 13 theme extracts 821:828 arg1 effects 804:810 the effects 800:810 the effects of these extracts on intracellular signal nodes and apoptotic pathways 800:881 Specifically we studied the effects of these extracts on intracellular signal nodes and apoptotic pathways. 26709080 6 14 theme several 1187:1193 arg1 proteins 1213:1220 several key intracellular proteins 1187:1220 several key intracellular proteins 1187:1220 Finally, to identify potential molecular targets causing the phenotypic changes in leukemic cell lines, we docked a selected group of these essential oils to several key intracellular proteins. 26709080 2 15 theme molecular 522:530 arg1 level 532:536 the molecular level 518:536 the molecular level 518:536 In this study, we studied the antileukemic activity of several chosen microalgae species at the molecular level and assessed their potential for drug development. 26709080 1 16 theme new 366:368 arg1 compounds 380:388 new bioactive compounds 366:388 new bioactive compounds with applications in biotechnology 366:423 Microalgae are very rich in bioactive compounds, minerals, polysaccharides, poly-unsaturated fatty acids and vitamins, and these rich constituents make microalgae an important resource for the discovery of new bioactive compounds with applications in biotechnology. 26709080 7 17 theme rank 1247:1250 arg1 score 1252:1256 rank score 1247:1256 rank score algorithm 1247:1266 According to results of rank score algorithm, five of these essential oils analyzed might be considered as in silico plausible candidates to be used as antileukemic agents. 26709080 4 18 theme signal 847:852 arg1 nodes 854:858 intracellular signal nodes 833:858 intracellular signal nodes 833:858 Specifically we studied the effects of these extracts on intracellular signal nodes and apoptotic pathways. 26709080 1 19 from applications 395:406 arg1 biotechnology 411:423 biotechnology 411:423 biotechnology 411:423 Microalgae are very rich in bioactive compounds, minerals, polysaccharides, poly-unsaturated fatty acids and vitamins, and these rich constituents make microalgae an important resource for the discovery of new bioactive compounds with applications in biotechnology. 26709080 1 20 theme bioactive 370:378 arg1 compounds 380:388 new bioactive compounds 366:388 new bioactive compounds with applications in biotechnology 366:423 Microalgae are very rich in bioactive compounds, minerals, polysaccharides, poly-unsaturated fatty acids and vitamins, and these rich constituents make microalgae an important resource for the discovery of new bioactive compounds with applications in biotechnology. 26709080 6 21 from changes 1101:1107 arg1 lines 1126:1130 leukemic cell lines 1112:1130 leukemic cell lines 1112:1130 Finally, to identify potential molecular targets causing the phenotypic changes in leukemic cell lines, we docked a selected group of these essential oils to several key intracellular proteins. 26709080 4 22 theme intracellular 833:845 arg1 nodes 854:858 intracellular signal nodes 833:858 intracellular signal nodes 833:858 Specifically we studied the effects of these extracts on intracellular signal nodes and apoptotic pathways. 26709080 7 23 theme score 1252:1256 arg1 algorithm 1258:1266 rank score algorithm 1247:1266 rank score algorithm 1247:1266 According to results of rank score algorithm, five of these essential oils analyzed might be considered as in silico plausible candidates to be used as antileukemic agents. 26709080 1 24 theme compounds 380:388 arg1 discovery 353:361 the discovery 349:361 the discovery of new bioactive compounds with applications in biotechnology 349:423 Microalgae are very rich in bioactive compounds, minerals, polysaccharides, poly-unsaturated fatty acids and vitamins, and these rich constituents make microalgae an important resource for the discovery of new bioactive compounds with applications in biotechnology. 26709080 7 25 theme oils 1293:1296 arg1 oils 1293:1296 these essential oils 1277:1296 these essential oils analyzed 1277:1305 According to results of rank score algorithm, five of these essential oils analyzed might be considered as in silico plausible candidates to be used as antileukemic agents. 26709080 7 25 theme oils 1293:1296 arg1 candidates 1350:1359 in silico plausible candidates 1330:1359 in silico plausible candidates 1330:1359 According to results of rank score algorithm, five of these essential oils analyzed might be considered as in silico plausible candidates to be used as antileukemic agents. 26709080 7 25 theme oils 1293:1296 arg1 five 1269:1272 five 1269:1272 five 1269:1272 According to results of rank score algorithm, five of these essential oils analyzed might be considered as in silico plausible candidates to be used as antileukemic agents. 26709080 7 25 theme oils 1293:1296 arg1 agents 1388:1393 antileukemic agents 1375:1393 antileukemic agents 1375:1393 According to results of rank score algorithm, five of these essential oils analyzed might be considered as in silico plausible candidates to be used as antileukemic agents. 26709080 7 26 theme in 1330:1331 arg1 oils 1293:1296 these essential oils 1277:1296 these essential oils analyzed 1277:1305 According to results of rank score algorithm, five of these essential oils analyzed might be considered as in silico plausible candidates to be used as antileukemic agents. 26709080 7 26 theme in 1330:1331 arg1 candidates 1350:1359 in silico plausible candidates 1330:1359 in silico plausible candidates 1330:1359 According to results of rank score algorithm, five of these essential oils analyzed might be considered as in silico plausible candidates to be used as antileukemic agents. 26709080 7 26 theme in 1330:1331 arg1 five 1269:1272 five 1269:1272 five 1269:1272 According to results of rank score algorithm, five of these essential oils analyzed might be considered as in silico plausible candidates to be used as antileukemic agents. 26709080 7 27 used used 1367:1370 arg2 oils 1293:1296 these essential oils 1277:1296 these essential oils analyzed 1277:1305 According to results of rank score algorithm, five of these essential oils analyzed might be considered as in silico plausible candidates to be used as antileukemic agents. 26709080 7 27 used used 1367:1370 arg2 candidates 1350:1359 in silico plausible candidates 1330:1359 in silico plausible candidates 1330:1359 According to results of rank score algorithm, five of these essential oils analyzed might be considered as in silico plausible candidates to be used as antileukemic agents. 26709080 7 27 used used 1367:1370 arg2 agents 1388:1393 antileukemic agents 1375:1393 antileukemic agents 1375:1393 According to results of rank score algorithm, five of these essential oils analyzed might be considered as in silico plausible candidates to be used as antileukemic agents. 26709080 7 27 used used 1367:1370 arg2 five 1269:1272 five 1269:1272 five 1269:1272 According to results of rank score algorithm, five of these essential oils analyzed might be considered as in silico plausible candidates to be used as antileukemic agents. 26709080 7 28 theme plausible 1340:1348 arg1 oils 1293:1296 these essential oils 1277:1296 these essential oils analyzed 1277:1305 According to results of rank score algorithm, five of these essential oils analyzed might be considered as in silico plausible candidates to be used as antileukemic agents. 26709080 7 28 theme plausible 1340:1348 arg1 candidates 1350:1359 in silico plausible candidates 1330:1359 in silico plausible candidates 1330:1359 According to results of rank score algorithm, five of these essential oils analyzed might be considered as in silico plausible candidates to be used as antileukemic agents. 26709080 7 28 theme plausible 1340:1348 arg1 five 1269:1272 five 1269:1272 five 1269:1272 According to results of rank score algorithm, five of these essential oils analyzed might be considered as in silico plausible candidates to be used as antileukemic agents. 26709080 6 29 theme selected 1145:1152 arg1 oils 1179:1182 these essential oils 1163:1182 these essential oils 1163:1182 Finally, to identify potential molecular targets causing the phenotypic changes in leukemic cell lines, we docked a selected group of these essential oils to several key intracellular proteins. 26709080 6 29 theme selected 1145:1152 arg1 group 1154:1158 a selected group 1143:1158 a selected group of these essential oils 1143:1182 Finally, to identify potential molecular targets causing the phenotypic changes in leukemic cell lines, we docked a selected group of these essential oils to several key intracellular proteins. 26709080 1 30 from acids 259:263 arg1 rich 180:183 rich 180:183 rich 180:183 Microalgae are very rich in bioactive compounds, minerals, polysaccharides, poly-unsaturated fatty acids and vitamins, and these rich constituents make microalgae an important resource for the discovery of new bioactive compounds with applications in biotechnology. 26709080 6 31 theme molecular 1060:1068 arg1 targets 1070:1076 potential molecular targets 1050:1076 potential molecular targets causing the phenotypic changes in leukemic cell lines 1050:1130 Finally, to identify potential molecular targets causing the phenotypic changes in leukemic cell lines, we docked a selected group of these essential oils to several key intracellular proteins. 26709080 3 32 theme microalgae 711:720 arg1 extracts 722:729 microalgae extracts 711:729 microalgae extracts 711:729 Here we identified Stichococcus bacillaris, Phaeodactylum tricornutum, Microcystis aeruginosa and Nannochloropsis oculata microalgae extracts with possible antileukemic agent potentials. 26709080 4 33 from effects 804:810 arg1 nodes 854:858 intracellular signal nodes 833:858 intracellular signal nodes 833:858 Specifically we studied the effects of these extracts on intracellular signal nodes and apoptotic pathways. 26709080 4 33 from effects 804:810 arg1 pathways 874:881 apoptotic pathways 864:881 apoptotic pathways 864:881 Specifically we studied the effects of these extracts on intracellular signal nodes and apoptotic pathways. 26709080 1 34 theme bioactive 188:196 arg1 compounds 198:206 bioactive compounds 188:206 bioactive compounds 188:206 Microalgae are very rich in bioactive compounds, minerals, polysaccharides, poly-unsaturated fatty acids and vitamins, and these rich constituents make microalgae an important resource for the discovery of new bioactive compounds with applications in biotechnology. 26709080 0 35 theme antileukemic 17:28 arg1 agents 30:35 new antileukemic agents 13:35 new antileukemic agents 13:35 Screening of new antileukemic agents from essential oils of algae extracts and computational modeling of their interactions with intracellular signaling nodes. 26709080 6 36 theme potential 1050:1058 arg1 targets 1070:1076 potential molecular targets 1050:1076 potential molecular targets causing the phenotypic changes in leukemic cell lines 1050:1130 Finally, to identify potential molecular targets causing the phenotypic changes in leukemic cell lines, we docked a selected group of these essential oils to several key intracellular proteins. 26709080 1 37 from vitamins 269:276 arg1 rich 180:183 rich 180:183 rich 180:183 Microalgae are very rich in bioactive compounds, minerals, polysaccharides, poly-unsaturated fatty acids and vitamins, and these rich constituents make microalgae an important resource for the discovery of new bioactive compounds with applications in biotechnology. 26709080 0 38 theme new 13:15 arg1 agents 30:35 new antileukemic agents 13:35 new antileukemic agents 13:35 Screening of new antileukemic agents from essential oils of algae extracts and computational modeling of their interactions with intracellular signaling nodes. 26709080 1 39 theme rich 289:292 arg1 constituents 294:305 these rich constituents 283:305 these rich constituents 283:305 Microalgae are very rich in bioactive compounds, minerals, polysaccharides, poly-unsaturated fatty acids and vitamins, and these rich constituents make microalgae an important resource for the discovery of new bioactive compounds with applications in biotechnology. 26709080 0 40 theme interactions 111:122 arg1 modeling 93:100 computational modeling 79:100 computational modeling of their interactions with intracellular signaling nodes 79:157 Screening of new antileukemic agents from essential oils of algae extracts and computational modeling of their interactions with intracellular signaling nodes. 26709080 0 40 theme interactions 111:122 arg1 oils 52:55 essential oils 42:55 essential oils of algae extracts 42:73 Screening of new antileukemic agents from essential oils of algae extracts and computational modeling of their interactions with intracellular signaling nodes. 26709080 7 41 dep in 1330:1331 arg1 silico 1333:1338 silico 1333:1338 silico 1333:1338 According to results of rank score algorithm, five of these essential oils analyzed might be considered as in silico plausible candidates to be used as antileukemic agents. 26709080 7 42 theme antileukemic 1375:1386 arg1 oils 1293:1296 these essential oils 1277:1296 these essential oils analyzed 1277:1305 According to results of rank score algorithm, five of these essential oils analyzed might be considered as in silico plausible candidates to be used as antileukemic agents. 26709080 7 42 theme antileukemic 1375:1386 arg1 five 1269:1272 five 1269:1272 five 1269:1272 According to results of rank score algorithm, five of these essential oils analyzed might be considered as in silico plausible candidates to be used as antileukemic agents. 26709080 7 42 theme antileukemic 1375:1386 arg1 agents 1388:1393 antileukemic agents 1375:1393 antileukemic agents 1375:1393 According to results of rank score algorithm, five of these essential oils analyzed might be considered as in silico plausible candidates to be used as antileukemic agents. 26709080 2 43 theme several 481:487 arg1 species 507:513 several chosen microalgae species 481:513 several chosen microalgae species 481:513 In this study, we studied the antileukemic activity of several chosen microalgae species at the molecular level and assessed their potential for drug development. 26709080 0 44 theme signaling 143:151 arg1 nodes 153:157 intracellular signaling nodes 129:157 intracellular signaling nodes 129:157 Screening of new antileukemic agents from essential oils of algae extracts and computational modeling of their interactions with intracellular signaling nodes. 26709080 7 45 theme algorithm 1258:1266 arg1 results 1236:1242 results 1236:1242 results of rank score algorithm 1236:1266 According to results of rank score algorithm, five of these essential oils analyzed might be considered as in silico plausible candidates to be used as antileukemic agents. 26709080 2 46 theme chosen 489:494 arg1 species 507:513 several chosen microalgae species 481:513 several chosen microalgae species 481:513 In this study, we studied the antileukemic activity of several chosen microalgae species at the molecular level and assessed their potential for drug development. 26709080 5 47 theme essential 920:928 arg1 oils 930:933 essential oils 920:933 essential oils of these fifteen different algae extracts 920:975 We characterized the composition of essential oils of these fifteen different algae extracts using gas chromatography-mass spectrometry (GC-MS). 26709080 0 48 theme agents 30:35 arg1 Screening 0:8 Screening 0:8 Screening of new antileukemic agents from essential oils of algae extracts and computational modeling of their interactions with intracellular signaling nodes. 0:158 Screening of new antileukemic agents from essential oils of algae extracts and computational modeling of their interactions with intracellular signaling nodes. 26709080 0 49 theme intracellular 129:141 arg1 nodes 153:157 intracellular signaling nodes 129:157 intracellular signaling nodes 129:157 Screening of new antileukemic agents from essential oils of algae extracts and computational modeling of their interactions with intracellular signaling nodes. 26709080 1 50 from minerals 209:216 arg1 rich 180:183 rich 180:183 rich 180:183 Microalgae are very rich in bioactive compounds, minerals, polysaccharides, poly-unsaturated fatty acids and vitamins, and these rich constituents make microalgae an important resource for the discovery of new bioactive compounds with applications in biotechnology. 26709080 5 51 theme oils 930:933 arg1 composition 905:915 the composition 901:915 the composition of essential oils of these fifteen different algae extracts 901:975 We characterized the composition of essential oils of these fifteen different algae extracts using gas chromatography-mass spectrometry (GC-MS). 26709080 5 52 theme chromatography-mass 987:1005 arg1 spectrometry 1007:1018 gas chromatography-mass spectrometry 983:1018 gas chromatography-mass spectrometry (GC-MS) 983:1026 We characterized the composition of essential oils of these fifteen different algae extracts using gas chromatography-mass spectrometry (GC-MS). 26709080 5 52 theme chromatography-mass 987:1005 arg1 GC-MS 1021:1025 GC-MS 1021:1025 GC-MS 1021:1025 We characterized the composition of essential oils of these fifteen different algae extracts using gas chromatography-mass spectrometry (GC-MS). 26709080 0 53 theme essential 42:50 arg1 oils 52:55 essential oils 42:55 essential oils of algae extracts 42:73 Screening of new antileukemic agents from essential oils of algae extracts and computational modeling of their interactions with intracellular signaling nodes. 26709080 2 54 theme antileukemic 456:467 arg1 activity 469:476 the antileukemic activity 452:476 the antileukemic activity of several chosen microalgae species at the molecular level 452:536 In this study, we studied the antileukemic activity of several chosen microalgae species at the molecular level and assessed their potential for drug development. 26709080 1 55 from compounds 198:206 arg1 rich 180:183 rich 180:183 rich 180:183 Microalgae are very rich in bioactive compounds, minerals, polysaccharides, poly-unsaturated fatty acids and vitamins, and these rich constituents make microalgae an important resource for the discovery of new bioactive compounds with applications in biotechnology. 26709080 6 56 theme intracellular 1199:1211 arg1 proteins 1213:1220 several key intracellular proteins 1187:1220 several key intracellular proteins 1187:1220 Finally, to identify potential molecular targets causing the phenotypic changes in leukemic cell lines, we docked a selected group of these essential oils to several key intracellular proteins. 26709080 1 57 theme important 326:334 arg1 resource 336:343 an important resource 323:343 an important resource for the discovery of new bioactive compounds with applications in biotechnology 323:423 Microalgae are very rich in bioactive compounds, minerals, polysaccharides, poly-unsaturated fatty acids and vitamins, and these rich constituents make microalgae an important resource for the discovery of new bioactive compounds with applications in biotechnology. 26709080 1 58 from polysaccharides 219:233 arg1 rich 180:183 rich 180:183 rich 180:183 Microalgae are very rich in bioactive compounds, minerals, polysaccharides, poly-unsaturated fatty acids and vitamins, and these rich constituents make microalgae an important resource for the discovery of new bioactive compounds with applications in biotechnology. 26709080 5 59 theme different 952:960 arg1 extracts 968:975 these fifteen different algae extracts 938:975 these fifteen different algae extracts 938:975 We characterized the composition of essential oils of these fifteen different algae extracts using gas chromatography-mass spectrometry (GC-MS). 26709080 6 60 theme key 1195:1197 arg1 proteins 1213:1220 several key intracellular proteins 1187:1220 several key intracellular proteins 1187:1220 Finally, to identify potential molecular targets causing the phenotypic changes in leukemic cell lines, we docked a selected group of these essential oils to several key intracellular proteins. 26709080 1 61 with compounds 380:388 arg1 applications 395:406 applications 395:406 applications in biotechnology 395:423 Microalgae are very rich in bioactive compounds, minerals, polysaccharides, poly-unsaturated fatty acids and vitamins, and these rich constituents make microalgae an important resource for the discovery of new bioactive compounds with applications in biotechnology. 26709080 6 62 theme cell 1121:1124 arg1 lines 1126:1130 leukemic cell lines 1112:1130 leukemic cell lines 1112:1130 Finally, to identify potential molecular targets causing the phenotypic changes in leukemic cell lines, we docked a selected group of these essential oils to several key intracellular proteins. 26709080 2 63 theme drug 571:574 arg1 development 576:586 drug development 571:586 drug development 571:586 In this study, we studied the antileukemic activity of several chosen microalgae species at the molecular level and assessed their potential for drug development. 26709080 0 64 from modeling 93:100 arg1 Screening 0:8 Screening 0:8 Screening of new antileukemic agents from essential oils of algae extracts and computational modeling of their interactions with intracellular signaling nodes. 0:158 Screening of new antileukemic agents from essential oils of algae extracts and computational modeling of their interactions with intracellular signaling nodes. 26709080 6 65 theme oils 1179:1182 arg1 oils 1179:1182 these essential oils 1163:1182 these essential oils 1163:1182 Finally, to identify potential molecular targets causing the phenotypic changes in leukemic cell lines, we docked a selected group of these essential oils to several key intracellular proteins. 26709080 6 65 theme oils 1179:1182 arg1 group 1154:1158 a selected group 1143:1158 a selected group of these essential oils 1143:1182 Finally, to identify potential molecular targets causing the phenotypic changes in leukemic cell lines, we docked a selected group of these essential oils to several key intracellular proteins. 26709080 6 66 theme leukemic 1112:1119 arg1 lines 1126:1130 leukemic cell lines 1112:1130 leukemic cell lines 1112:1130 Finally, to identify potential molecular targets causing the phenotypic changes in leukemic cell lines, we docked a selected group of these essential oils to several key intracellular proteins. 26709080 0 67 theme algae 60:64 arg1 extracts 66:73 algae extracts 60:73 algae extracts 60:73 Screening of new antileukemic agents from essential oils of algae extracts and computational modeling of their interactions with intracellular signaling nodes. 26709080 2 68 from level 532:536 arg1 activity 469:476 the antileukemic activity 452:476 the antileukemic activity of several chosen microalgae species at the molecular level 452:536 In this study, we studied the antileukemic activity of several chosen microalgae species at the molecular level and assessed their potential for drug development. 26709080 5 69 theme algae 962:966 arg1 extracts 968:975 these fifteen different algae extracts 938:975 these fifteen different algae extracts 938:975 We characterized the composition of essential oils of these fifteen different algae extracts using gas chromatography-mass spectrometry (GC-MS). 26709080 0 70 with interactions 111:122 arg1 nodes 153:157 intracellular signaling nodes 129:157 intracellular signaling nodes 129:157 Screening of new antileukemic agents from essential oils of algae extracts and computational modeling of their interactions with intracellular signaling nodes. 26709080 1 71 theme poly-unsaturated 236:251 arg1 acids 259:263 poly-unsaturated fatty acids 236:263 poly-unsaturated fatty acids 236:263 Microalgae are very rich in bioactive compounds, minerals, polysaccharides, poly-unsaturated fatty acids and vitamins, and these rich constituents make microalgae an important resource for the discovery of new bioactive compounds with applications in biotechnology. 26709080 2 72 theme species 507:513 arg1 activity 469:476 the antileukemic activity 452:476 the antileukemic activity of several chosen microalgae species at the molecular level 452:536 In this study, we studied the antileukemic activity of several chosen microalgae species at the molecular level and assessed their potential for drug development. 26709080 4 73 theme apoptotic 864:872 arg1 pathways 874:881 apoptotic pathways 864:881 apoptotic pathways 864:881 Specifically we studied the effects of these extracts on intracellular signal nodes and apoptotic pathways. 26709080 5 74 theme extracts 968:975 arg1 oils 930:933 essential oils 920:933 essential oils of these fifteen different algae extracts 920:975 We characterized the composition of essential oils of these fifteen different algae extracts using gas chromatography-mass spectrometry (GC-MS). 26709080 1 75 theme fatty 253:257 arg1 acids 259:263 poly-unsaturated fatty acids 236:263 poly-unsaturated fatty acids 236:263 Microalgae are very rich in bioactive compounds, minerals, polysaccharides, poly-unsaturated fatty acids and vitamins, and these rich constituents make microalgae an important resource for the discovery of new bioactive compounds with applications in biotechnology. 25430540 9 0 theme DISCUSSION 1673:1682 arg1 Data 1699:1702 DISCUSSION AND CONCLUSION Data 1673:1702 DISCUSSION AND CONCLUSION Data 1673:1702 DISCUSSION AND CONCLUSION Data showed that non-polar fractions of E. triplinerve methanolic extract has better antimicrobial activity and most likely depends on the presence of several compounds, such as depsidones, coumarins, saponins, and triterpenes on crude extract. 25430540 6 1 theme polysaccharides 1294:1308 arg1 coumarins 1229:1237 coumarins 1229:1237 coumarins 1229:1237 RESULTS Phytochemical screening of hydroalcoholic extract from all parts of E. triplinerve identified mainly steroids, coumarins, alkaloids, saponins, tannins, depsides and absence of polysaccharides and flavonoids. 25430540 6 1 theme polysaccharides 1294:1308 arg1 tannins 1261:1267 tannins 1261:1267 tannins 1261:1267 RESULTS Phytochemical screening of hydroalcoholic extract from all parts of E. triplinerve identified mainly steroids, coumarins, alkaloids, saponins, tannins, depsides and absence of polysaccharides and flavonoids. 25430540 6 1 theme polysaccharides 1294:1308 arg1 depsides 1270:1277 depsides 1270:1277 depsides 1270:1277 RESULTS Phytochemical screening of hydroalcoholic extract from all parts of E. triplinerve identified mainly steroids, coumarins, alkaloids, saponins, tannins, depsides and absence of polysaccharides and flavonoids. 25430540 6 1 theme polysaccharides 1294:1308 arg1 alkaloids 1240:1248 alkaloids 1240:1248 alkaloids 1240:1248 RESULTS Phytochemical screening of hydroalcoholic extract from all parts of E. triplinerve identified mainly steroids, coumarins, alkaloids, saponins, tannins, depsides and absence of polysaccharides and flavonoids. 25430540 6 1 theme polysaccharides 1294:1308 arg1 saponins 1251:1258 saponins 1251:1258 saponins 1251:1258 RESULTS Phytochemical screening of hydroalcoholic extract from all parts of E. triplinerve identified mainly steroids, coumarins, alkaloids, saponins, tannins, depsides and absence of polysaccharides and flavonoids. 25430540 6 1 theme polysaccharides 1294:1308 arg1 absence 1283:1289 absence 1283:1289 absence of polysaccharides and flavonoids 1283:1323 RESULTS Phytochemical screening of hydroalcoholic extract from all parts of E. triplinerve identified mainly steroids, coumarins, alkaloids, saponins, tannins, depsides and absence of polysaccharides and flavonoids. 25430540 6 1 theme polysaccharides 1294:1308 arg1 steroids 1219:1226 steroids 1219:1226 steroids 1219:1226 RESULTS Phytochemical screening of hydroalcoholic extract from all parts of E. triplinerve identified mainly steroids, coumarins, alkaloids, saponins, tannins, depsides and absence of polysaccharides and flavonoids. 25430540 9 2 theme CONCLUSION 1688:1697 arg1 Data 1699:1702 DISCUSSION AND CONCLUSION Data 1673:1702 DISCUSSION AND CONCLUSION Data 1673:1702 DISCUSSION AND CONCLUSION Data showed that non-polar fractions of E. triplinerve methanolic extract has better antimicrobial activity and most likely depends on the presence of several compounds, such as depsidones, coumarins, saponins, and triterpenes on crude extract. 25430540 9 3 theme crude 1929:1933 arg1 extract 1935:1941 crude extract 1929:1941 crude extract 1929:1941 DISCUSSION AND CONCLUSION Data showed that non-polar fractions of E. triplinerve methanolic extract has better antimicrobial activity and most likely depends on the presence of several compounds, such as depsidones, coumarins, saponins, and triterpenes on crude extract. 25430540 1 4 theme Eupatorium 101:110 arg1 Asteraceae 130:139 Asteraceae 130:139 Asteraceae 130:139 CONTEXT Eupatorium triplinerve Vahl (Asteraceae), popularly known as Japana, is widely used in folk medicine, due its analgesic, anticoagulant, antianorexic, antiparasitic, anthelmintic, sedative, antifungal, and antibacterial properties. 25430540 1 4 theme Eupatorium 101:110 arg1 Vahl 124:127 CONTEXT Eupatorium triplinerve Vahl 93:127 CONTEXT Eupatorium triplinerve Vahl (Asteraceae) 93:140 CONTEXT Eupatorium triplinerve Vahl (Asteraceae), popularly known as Japana, is widely used in folk medicine, due its analgesic, anticoagulant, antianorexic, antiparasitic, anthelmintic, sedative, antifungal, and antibacterial properties. 25430540 9 5 contain has 1773:1775 arg2 activity 1798:1805 better antimicrobial activity 1777:1805 better antimicrobial activity 1777:1805 DISCUSSION AND CONCLUSION Data showed that non-polar fractions of E. triplinerve methanolic extract has better antimicrobial activity and most likely depends on the presence of several compounds, such as depsidones, coumarins, saponins, and triterpenes on crude extract. 25430540 9 5 contain has 1773:1775 arg1 fractions 1726:1734 non-polar fractions 1716:1734 non-polar fractions of E. triplinerve methanolic extract 1716:1771 DISCUSSION AND CONCLUSION Data showed that non-polar fractions of E. triplinerve methanolic extract has better antimicrobial activity and most likely depends on the presence of several compounds, such as depsidones, coumarins, saponins, and triterpenes on crude extract. 25430540 6 6 theme triplinerve 1189:1199 arg1 parts 1177:1181 all parts 1173:1181 all parts of E. triplinerve 1173:1199 RESULTS Phytochemical screening of hydroalcoholic extract from all parts of E. triplinerve identified mainly steroids, coumarins, alkaloids, saponins, tannins, depsides and absence of polysaccharides and flavonoids. 25430540 9 7 theme non-polar 1716:1724 arg1 fractions 1726:1734 non-polar fractions 1716:1734 non-polar fractions of E. triplinerve methanolic extract 1716:1771 DISCUSSION AND CONCLUSION Data showed that non-polar fractions of E. triplinerve methanolic extract has better antimicrobial activity and most likely depends on the presence of several compounds, such as depsidones, coumarins, saponins, and triterpenes on crude extract. 25430540 9 8 from saponins 1900:1907 arg1 extract 1935:1941 crude extract 1929:1941 crude extract 1929:1941 DISCUSSION AND CONCLUSION Data showed that non-polar fractions of E. triplinerve methanolic extract has better antimicrobial activity and most likely depends on the presence of several compounds, such as depsidones, coumarins, saponins, and triterpenes on crude extract. 25430540 10 9 theme new 1996:1998 arg1 agents 2014:2019 new antibacterial agents 1996:2019 new antibacterial agents 1996:2019 The results can be exploited largely in research of new antibacterial agents. 25430540 7 10 theme values 1414:1419 arg1 content 1379:1385 the highest content 1367:1385 the highest content of coumarins and lower MIC values of 62 and 75 µg/mL against Enterococcus faecalis and Staphylococcus aureus, respectively 1367:1508 The methanol extract of leaves presented the highest content of coumarins and lower MIC values of 62 and 75 µg/mL against Enterococcus faecalis and Staphylococcus aureus, respectively. 25430540 5 11 theme extracts 950:957 arg1 activity 924:931 The antimicrobial activity 906:931 The antimicrobial activity of the different extracts 906:957 The antimicrobial activity of the different extracts was performed by microdilution assay and the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values were reported. 25430540 9 12 theme triplinerve 1742:1752 arg1 extract 1765:1771 E. triplinerve methanolic extract 1739:1771 E. triplinerve methanolic extract 1739:1771 DISCUSSION AND CONCLUSION Data showed that non-polar fractions of E. triplinerve methanolic extract has better antimicrobial activity and most likely depends on the presence of several compounds, such as depsidones, coumarins, saponins, and triterpenes on crude extract. 25430540 7 13 theme lower 1404:1408 arg1 values 1414:1419 lower MIC values 1404:1419 lower MIC values of 62 and 75 µg/mL against Enterococcus faecalis and Staphylococcus aureus, respectively 1404:1508 The methanol extract of leaves presented the highest content of coumarins and lower MIC values of 62 and 75 µg/mL against Enterococcus faecalis and Staphylococcus aureus, respectively. 25430540 2 14 theme extracts 440:447 arg1 composition 383:393 chemical composition 374:393 chemical composition 374:393 OBJECTIVE The present study evaluated the chemical composition and antimicrobial activity of E. triplinerve extracts from different parts of the plant and identified the extract with the highest antimicrobial potential. 25430540 2 14 theme extracts 440:447 arg1 activity 413:420 antimicrobial activity 399:420 antimicrobial activity 399:420 OBJECTIVE The present study evaluated the chemical composition and antimicrobial activity of E. triplinerve extracts from different parts of the plant and identified the extract with the highest antimicrobial potential. 25430540 9 15 theme extract 1765:1771 arg1 fractions 1726:1734 non-polar fractions 1716:1734 non-polar fractions of E. triplinerve methanolic extract 1716:1771 DISCUSSION AND CONCLUSION Data showed that non-polar fractions of E. triplinerve methanolic extract has better antimicrobial activity and most likely depends on the presence of several compounds, such as depsidones, coumarins, saponins, and triterpenes on crude extract. 25430540 1 16 dep analgesic 211:219 arg1 antianorexic 237:248 antianorexic 237:248 antianorexic 237:248 CONTEXT Eupatorium triplinerve Vahl (Asteraceae), popularly known as Japana, is widely used in folk medicine, due its analgesic, anticoagulant, antianorexic, antiparasitic, anthelmintic, sedative, antifungal, and antibacterial properties. 25430540 1 16 dep analgesic 211:219 arg1 sedative 280:287 sedative 280:287 sedative 280:287 CONTEXT Eupatorium triplinerve Vahl (Asteraceae), popularly known as Japana, is widely used in folk medicine, due its analgesic, anticoagulant, antianorexic, antiparasitic, anthelmintic, sedative, antifungal, and antibacterial properties. 25430540 1 16 dep analgesic 211:219 arg1 anthelmintic 266:277 anthelmintic 266:277 anthelmintic 266:277 CONTEXT Eupatorium triplinerve Vahl (Asteraceae), popularly known as Japana, is widely used in folk medicine, due its analgesic, anticoagulant, antianorexic, antiparasitic, anthelmintic, sedative, antifungal, and antibacterial properties. 25430540 1 16 dep analgesic 211:219 arg1 anticoagulant 222:234 anticoagulant 222:234 anticoagulant 222:234 CONTEXT Eupatorium triplinerve Vahl (Asteraceae), popularly known as Japana, is widely used in folk medicine, due its analgesic, anticoagulant, antianorexic, antiparasitic, anthelmintic, sedative, antifungal, and antibacterial properties. 25430540 1 16 dep analgesic 211:219 arg1 antiparasitic 251:263 antiparasitic 251:263 antiparasitic 251:263 CONTEXT Eupatorium triplinerve Vahl (Asteraceae), popularly known as Japana, is widely used in folk medicine, due its analgesic, anticoagulant, antianorexic, antiparasitic, anthelmintic, sedative, antifungal, and antibacterial properties. 25430540 7 17 theme coumarins 1390:1398 arg1 content 1379:1385 the highest content 1367:1385 the highest content of coumarins and lower MIC values of 62 and 75 µg/mL against Enterococcus faecalis and Staphylococcus aureus, respectively 1367:1508 The methanol extract of leaves presented the highest content of coumarins and lower MIC values of 62 and 75 µg/mL against Enterococcus faecalis and Staphylococcus aureus, respectively. 25430540 10 18 theme agents 2014:2019 arg1 research 1984:1991 research 1984:1991 research of new antibacterial agents 1984:2019 The results can be exploited largely in research of new antibacterial agents. 25430540 5 19 theme minimum 1047:1053 arg1 concentration 1068:1080 minimum bactericidal concentration 1047:1080 minimum bactericidal concentration (MBC) 1047:1086 The antimicrobial activity of the different extracts was performed by microdilution assay and the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values were reported. 25430540 5 19 theme minimum 1047:1053 arg1 MBC 1083:1085 MBC 1083:1085 MBC 1083:1085 The antimicrobial activity of the different extracts was performed by microdilution assay and the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values were reported. 25430540 9 20 theme better 1777:1782 arg1 activity 1798:1805 better antimicrobial activity 1777:1805 better antimicrobial activity 1777:1805 DISCUSSION AND CONCLUSION Data showed that non-polar fractions of E. triplinerve methanolic extract has better antimicrobial activity and most likely depends on the presence of several compounds, such as depsidones, coumarins, saponins, and triterpenes on crude extract. 25430540 4 21 theme chemical 747:754 arg1 triterpenoids 812:824 triterpenoids 812:824 triterpenoids 812:824 The major chemical groups, saponins, reducing sugars, alkaloids, steroids, triterpenoids, phenols, tannins, flavonoids, and others were screened by standard techniques. 25430540 4 21 theme chemical 747:754 arg1 flavonoids 845:854 flavonoids 845:854 flavonoids 845:854 The major chemical groups, saponins, reducing sugars, alkaloids, steroids, triterpenoids, phenols, tannins, flavonoids, and others were screened by standard techniques. 25430540 4 21 theme chemical 747:754 arg1 sugars 783:788 reducing sugars 774:788 reducing sugars 774:788 The major chemical groups, saponins, reducing sugars, alkaloids, steroids, triterpenoids, phenols, tannins, flavonoids, and others were screened by standard techniques. 25430540 4 21 theme chemical 747:754 arg1 alkaloids 791:799 alkaloids 791:799 alkaloids 791:799 The major chemical groups, saponins, reducing sugars, alkaloids, steroids, triterpenoids, phenols, tannins, flavonoids, and others were screened by standard techniques. 25430540 4 21 theme chemical 747:754 arg1 phenols 827:833 phenols 827:833 phenols 827:833 The major chemical groups, saponins, reducing sugars, alkaloids, steroids, triterpenoids, phenols, tannins, flavonoids, and others were screened by standard techniques. 25430540 4 21 theme chemical 747:754 arg1 groups 756:761 The major chemical groups 737:761 The major chemical groups 737:761 The major chemical groups, saponins, reducing sugars, alkaloids, steroids, triterpenoids, phenols, tannins, flavonoids, and others were screened by standard techniques. 25430540 4 21 theme chemical 747:754 arg1 others 861:866 others 861:866 others 861:866 The major chemical groups, saponins, reducing sugars, alkaloids, steroids, triterpenoids, phenols, tannins, flavonoids, and others were screened by standard techniques. 25430540 4 21 theme chemical 747:754 arg1 tannins 836:842 tannins 836:842 tannins 836:842 The major chemical groups, saponins, reducing sugars, alkaloids, steroids, triterpenoids, phenols, tannins, flavonoids, and others were screened by standard techniques. 25430540 4 21 theme chemical 747:754 arg1 saponins 764:771 saponins 764:771 saponins 764:771 The major chemical groups, saponins, reducing sugars, alkaloids, steroids, triterpenoids, phenols, tannins, flavonoids, and others were screened by standard techniques. 25430540 4 21 theme chemical 747:754 arg1 steroids 802:809 steroids 802:809 steroids 802:809 The major chemical groups, saponins, reducing sugars, alkaloids, steroids, triterpenoids, phenols, tannins, flavonoids, and others were screened by standard techniques. 25430540 6 22 theme flavonoids 1314:1323 arg1 coumarins 1229:1237 coumarins 1229:1237 coumarins 1229:1237 RESULTS Phytochemical screening of hydroalcoholic extract from all parts of E. triplinerve identified mainly steroids, coumarins, alkaloids, saponins, tannins, depsides and absence of polysaccharides and flavonoids. 25430540 6 22 theme flavonoids 1314:1323 arg1 tannins 1261:1267 tannins 1261:1267 tannins 1261:1267 RESULTS Phytochemical screening of hydroalcoholic extract from all parts of E. triplinerve identified mainly steroids, coumarins, alkaloids, saponins, tannins, depsides and absence of polysaccharides and flavonoids. 25430540 6 22 theme flavonoids 1314:1323 arg1 depsides 1270:1277 depsides 1270:1277 depsides 1270:1277 RESULTS Phytochemical screening of hydroalcoholic extract from all parts of E. triplinerve identified mainly steroids, coumarins, alkaloids, saponins, tannins, depsides and absence of polysaccharides and flavonoids. 25430540 6 22 theme flavonoids 1314:1323 arg1 alkaloids 1240:1248 alkaloids 1240:1248 alkaloids 1240:1248 RESULTS Phytochemical screening of hydroalcoholic extract from all parts of E. triplinerve identified mainly steroids, coumarins, alkaloids, saponins, tannins, depsides and absence of polysaccharides and flavonoids. 25430540 6 22 theme flavonoids 1314:1323 arg1 saponins 1251:1258 saponins 1251:1258 saponins 1251:1258 RESULTS Phytochemical screening of hydroalcoholic extract from all parts of E. triplinerve identified mainly steroids, coumarins, alkaloids, saponins, tannins, depsides and absence of polysaccharides and flavonoids. 25430540 6 22 theme flavonoids 1314:1323 arg1 absence 1283:1289 absence 1283:1289 absence of polysaccharides and flavonoids 1283:1323 RESULTS Phytochemical screening of hydroalcoholic extract from all parts of E. triplinerve identified mainly steroids, coumarins, alkaloids, saponins, tannins, depsides and absence of polysaccharides and flavonoids. 25430540 6 22 theme flavonoids 1314:1323 arg1 steroids 1219:1226 steroids 1219:1226 steroids 1219:1226 RESULTS Phytochemical screening of hydroalcoholic extract from all parts of E. triplinerve identified mainly steroids, coumarins, alkaloids, saponins, tannins, depsides and absence of polysaccharides and flavonoids. 25430540 5 23 theme concentration 1068:1080 arg1 values 1088:1093 the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values 1000:1093 the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values 1000:1093 The antimicrobial activity of the different extracts was performed by microdilution assay and the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values were reported. 25430540 0 24 theme Eupatorium 69:78 arg1 extract 58:64 a methanol extract 47:64 a methanol extract of Eupatorium 47:78 Antimicrobial bioassay-guided fractionation of a methanol extract of Eupatorium triplinerve. 25430540 1 25 theme antibacterial 306:318 arg1 properties 320:329 antibacterial properties 306:329 antibacterial properties 306:329 CONTEXT Eupatorium triplinerve Vahl (Asteraceae), popularly known as Japana, is widely used in folk medicine, due its analgesic, anticoagulant, antianorexic, antiparasitic, anthelmintic, sedative, antifungal, and antibacterial properties. 25430540 2 26 theme antimicrobial 527:539 arg1 potential 541:549 the highest antimicrobial potential 515:549 the highest antimicrobial potential 515:549 OBJECTIVE The present study evaluated the chemical composition and antimicrobial activity of E. triplinerve extracts from different parts of the plant and identified the extract with the highest antimicrobial potential. 25430540 6 27 theme E. 1186:1187 arg1 triplinerve 1189:1199 E. triplinerve 1186:1199 E. triplinerve 1186:1199 RESULTS Phytochemical screening of hydroalcoholic extract from all parts of E. triplinerve identified mainly steroids, coumarins, alkaloids, saponins, tannins, depsides and absence of polysaccharides and flavonoids. 25430540 2 28 with extract 502:508 arg1 potential 541:549 the highest antimicrobial potential 515:549 the highest antimicrobial potential 515:549 OBJECTIVE The present study evaluated the chemical composition and antimicrobial activity of E. triplinerve extracts from different parts of the plant and identified the extract with the highest antimicrobial potential. 25430540 5 29 theme microdilution 976:988 arg1 assay 990:994 microdilution assay 976:994 microdilution assay 976:994 The antimicrobial activity of the different extracts was performed by microdilution assay and the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values were reported. 25430540 2 30 from parts 464:468 arg1 composition 383:393 chemical composition 374:393 chemical composition 374:393 OBJECTIVE The present study evaluated the chemical composition and antimicrobial activity of E. triplinerve extracts from different parts of the plant and identified the extract with the highest antimicrobial potential. 25430540 2 30 from parts 464:468 arg1 activity 413:420 antimicrobial activity 399:420 antimicrobial activity 399:420 OBJECTIVE The present study evaluated the chemical composition and antimicrobial activity of E. triplinerve extracts from different parts of the plant and identified the extract with the highest antimicrobial potential. 25430540 1 31 theme CONTEXT 93:99 arg1 Asteraceae 130:139 Asteraceae 130:139 Asteraceae 130:139 CONTEXT Eupatorium triplinerve Vahl (Asteraceae), popularly known as Japana, is widely used in folk medicine, due its analgesic, anticoagulant, antianorexic, antiparasitic, anthelmintic, sedative, antifungal, and antibacterial properties. 25430540 1 31 theme CONTEXT 93:99 arg1 Vahl 124:127 CONTEXT Eupatorium triplinerve Vahl 93:127 CONTEXT Eupatorium triplinerve Vahl (Asteraceae) 93:140 CONTEXT Eupatorium triplinerve Vahl (Asteraceae), popularly known as Japana, is widely used in folk medicine, due its analgesic, anticoagulant, antianorexic, antiparasitic, anthelmintic, sedative, antifungal, and antibacterial properties. 25430540 2 32 theme different 454:462 arg1 parts 464:468 different parts 454:468 different parts of the plant 454:481 OBJECTIVE The present study evaluated the chemical composition and antimicrobial activity of E. triplinerve extracts from different parts of the plant and identified the extract with the highest antimicrobial potential. 25430540 8 33 theme antimicrobial 1555:1567 arg1 activity 1569:1576 antimicrobial activity 1555:1576 antimicrobial activity 1555:1576 In addition, its non-polar fractions showed antimicrobial activity with MIC ranging from 16 to 125 µg/mL against Gram-negative bacteria, mainly Escherichia coli. 25430540 2 34 theme chemical 374:381 arg1 composition 383:393 chemical composition 374:393 chemical composition 374:393 OBJECTIVE The present study evaluated the chemical composition and antimicrobial activity of E. triplinerve extracts from different parts of the plant and identified the extract with the highest antimicrobial potential. 25430540 0 35 theme Antimicrobial 0:12 arg1 fractionation 30:42 Antimicrobial bioassay-guided fractionation 0:42 Antimicrobial bioassay-guided fractionation of a methanol extract of Eupatorium 0:78 Antimicrobial bioassay-guided fractionation of a methanol extract of Eupatorium triplinerve. 25430540 1 36 theme triplinerve 112:122 arg1 Asteraceae 130:139 Asteraceae 130:139 Asteraceae 130:139 CONTEXT Eupatorium triplinerve Vahl (Asteraceae), popularly known as Japana, is widely used in folk medicine, due its analgesic, anticoagulant, antianorexic, antiparasitic, anthelmintic, sedative, antifungal, and antibacterial properties. 25430540 1 36 theme triplinerve 112:122 arg1 Vahl 124:127 CONTEXT Eupatorium triplinerve Vahl 93:127 CONTEXT Eupatorium triplinerve Vahl (Asteraceae) 93:140 CONTEXT Eupatorium triplinerve Vahl (Asteraceae), popularly known as Japana, is widely used in folk medicine, due its analgesic, anticoagulant, antianorexic, antiparasitic, anthelmintic, sedative, antifungal, and antibacterial properties. 25430540 9 37 theme compounds 1858:1866 arg1 presence 1838:1845 the presence 1834:1845 the presence of several compounds, such as depsidones, coumarins, saponins, and triterpenes on crude extract 1834:1941 DISCUSSION AND CONCLUSION Data showed that non-polar fractions of E. triplinerve methanolic extract has better antimicrobial activity and most likely depends on the presence of several compounds, such as depsidones, coumarins, saponins, and triterpenes on crude extract. 25430540 2 38 dep OBJECTIVE 332:340 arg1 identified 487:496 identified 487:496 identified the extract with the highest antimicrobial potential 487:549 OBJECTIVE The present study evaluated the chemical composition and antimicrobial activity of E. triplinerve extracts from different parts of the plant and identified the extract with the highest antimicrobial potential. 25430540 2 38 dep OBJECTIVE 332:340 arg1 evaluated 360:368 evaluated 360:368 evaluated the chemical composition and antimicrobial activity of E. triplinerve extracts from different parts of the plant 360:481 OBJECTIVE The present study evaluated the chemical composition and antimicrobial activity of E. triplinerve extracts from different parts of the plant and identified the extract with the highest antimicrobial potential. 25430540 2 39 theme E. 425:426 arg1 extracts 440:447 E. triplinerve extracts 425:447 E. triplinerve extracts 425:447 OBJECTIVE The present study evaluated the chemical composition and antimicrobial activity of E. triplinerve extracts from different parts of the plant and identified the extract with the highest antimicrobial potential. 25430540 7 40 theme methanol 1330:1337 arg1 extract 1339:1345 The methanol extract 1326:1345 The methanol extract of leaves 1326:1355 The methanol extract of leaves presented the highest content of coumarins and lower MIC values of 62 and 75 µg/mL against Enterococcus faecalis and Staphylococcus aureus, respectively. 25430540 2 41 theme plant 477:481 arg1 parts 464:468 different parts 454:468 different parts of the plant 454:481 OBJECTIVE The present study evaluated the chemical composition and antimicrobial activity of E. triplinerve extracts from different parts of the plant and identified the extract with the highest antimicrobial potential. 25430540 3 42 theme bioassay-guided 651:665 arg1 fractionation 667:679 bioassay-guided fractionation 651:679 bioassay-guided fractionation of methanol extract by partition column chromatography 651:734 MATERIALS AND METHODS Extracts were obtained by maceration of all parts of plant, and subjected to bioassay-guided fractionation of methanol extract by partition column chromatography. 25430540 6 43 from parts 1177:1181 arg1 screening 1132:1140 RESULTS Phytochemical screening 1110:1140 RESULTS Phytochemical screening of hydroalcoholic extract from all parts of E. triplinerve 1110:1199 RESULTS Phytochemical screening of hydroalcoholic extract from all parts of E. triplinerve identified mainly steroids, coumarins, alkaloids, saponins, tannins, depsides and absence of polysaccharides and flavonoids. 25430540 6 43 from parts 1177:1181 arg1 extract 1160:1166 hydroalcoholic extract 1145:1166 hydroalcoholic extract from all parts of E. triplinerve 1145:1199 RESULTS Phytochemical screening of hydroalcoholic extract from all parts of E. triplinerve identified mainly steroids, coumarins, alkaloids, saponins, tannins, depsides and absence of polysaccharides and flavonoids. 25430540 6 44 from screening 1132:1140 arg1 parts 1177:1181 all parts 1173:1181 all parts of E. triplinerve 1173:1199 RESULTS Phytochemical screening of hydroalcoholic extract from all parts of E. triplinerve identified mainly steroids, coumarins, alkaloids, saponins, tannins, depsides and absence of polysaccharides and flavonoids. 25430540 0 45 theme extract 58:64 arg1 fractionation 30:42 Antimicrobial bioassay-guided fractionation 0:42 Antimicrobial bioassay-guided fractionation of a methanol extract of Eupatorium 0:78 Antimicrobial bioassay-guided fractionation of a methanol extract of Eupatorium triplinerve. 25430540 6 46 theme hydroalcoholic 1145:1158 arg1 extract 1160:1166 hydroalcoholic extract 1145:1166 hydroalcoholic extract from all parts of E. triplinerve 1145:1199 RESULTS Phytochemical screening of hydroalcoholic extract from all parts of E. triplinerve identified mainly steroids, coumarins, alkaloids, saponins, tannins, depsides and absence of polysaccharides and flavonoids. 25430540 3 47 theme extract 693:699 arg1 fractionation 667:679 bioassay-guided fractionation 651:679 bioassay-guided fractionation of methanol extract by partition column chromatography 651:734 MATERIALS AND METHODS Extracts were obtained by maceration of all parts of plant, and subjected to bioassay-guided fractionation of methanol extract by partition column chromatography. 25430540 9 48 from triterpenes 1914:1924 arg1 extract 1935:1941 crude extract 1929:1941 crude extract 1929:1941 DISCUSSION AND CONCLUSION Data showed that non-polar fractions of E. triplinerve methanolic extract has better antimicrobial activity and most likely depends on the presence of several compounds, such as depsidones, coumarins, saponins, and triterpenes on crude extract. 25430540 5 49 theme minimum 1004:1010 arg1 MIC 1038:1040 MIC 1038:1040 MIC 1038:1040 The antimicrobial activity of the different extracts was performed by microdilution assay and the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values were reported. 25430540 5 49 theme minimum 1004:1010 arg1 concentration 1023:1035 minimum inhibitory concentration 1004:1035 minimum inhibitory concentration (MIC) 1004:1041 The antimicrobial activity of the different extracts was performed by microdilution assay and the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values were reported. 25430540 9 50 from depsidones 1877:1886 arg1 extract 1935:1941 crude extract 1929:1941 crude extract 1929:1941 DISCUSSION AND CONCLUSION Data showed that non-polar fractions of E. triplinerve methanolic extract has better antimicrobial activity and most likely depends on the presence of several compounds, such as depsidones, coumarins, saponins, and triterpenes on crude extract. 25430540 5 51 theme concentration 1023:1035 arg1 values 1088:1093 the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values 1000:1093 the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values 1000:1093 The antimicrobial activity of the different extracts was performed by microdilution assay and the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values were reported. 25430540 6 52 theme RESULTS 1110:1116 arg1 screening 1132:1140 RESULTS Phytochemical screening 1110:1140 RESULTS Phytochemical screening of hydroalcoholic extract from all parts of E. triplinerve 1110:1199 RESULTS Phytochemical screening of hydroalcoholic extract from all parts of E. triplinerve identified mainly steroids, coumarins, alkaloids, saponins, tannins, depsides and absence of polysaccharides and flavonoids. 25430540 2 53 theme present 346:352 arg1 study 354:358 The present study 342:358 The present study 342:358 OBJECTIVE The present study evaluated the chemical composition and antimicrobial activity of E. triplinerve extracts from different parts of the plant and identified the extract with the highest antimicrobial potential. 25430540 3 54 theme partition 704:712 arg1 chromatography 721:734 partition column chromatography 704:734 partition column chromatography 704:734 MATERIALS AND METHODS Extracts were obtained by maceration of all parts of plant, and subjected to bioassay-guided fractionation of methanol extract by partition column chromatography. 25430540 7 55 theme µg/mL 1434:1438 arg1 values 1414:1419 lower MIC values 1404:1419 lower MIC values of 62 and 75 µg/mL against Enterococcus faecalis and Staphylococcus aureus, respectively 1404:1508 The methanol extract of leaves presented the highest content of coumarins and lower MIC values of 62 and 75 µg/mL against Enterococcus faecalis and Staphylococcus aureus, respectively. 25430540 7 55 theme µg/mL 1434:1438 arg1 coumarins 1390:1398 coumarins 1390:1398 coumarins 1390:1398 The methanol extract of leaves presented the highest content of coumarins and lower MIC values of 62 and 75 µg/mL against Enterococcus faecalis and Staphylococcus aureus, respectively. 25430540 1 56 theme folk 188:191 arg1 medicine 193:200 folk medicine 188:200 folk medicine 188:200 CONTEXT Eupatorium triplinerve Vahl (Asteraceae), popularly known as Japana, is widely used in folk medicine, due its analgesic, anticoagulant, antianorexic, antiparasitic, anthelmintic, sedative, antifungal, and antibacterial properties. 25430540 9 57 theme E. 1739:1740 arg1 extract 1765:1771 E. triplinerve methanolic extract 1739:1771 E. triplinerve methanolic extract 1739:1771 DISCUSSION AND CONCLUSION Data showed that non-polar fractions of E. triplinerve methanolic extract has better antimicrobial activity and most likely depends on the presence of several compounds, such as depsidones, coumarins, saponins, and triterpenes on crude extract. 25430540 8 58 dep 125 1606:1608 arg1 to 1603:1604 to 1603:1604 to 1603:1604 In addition, its non-polar fractions showed antimicrobial activity with MIC ranging from 16 to 125 µg/mL against Gram-negative bacteria, mainly Escherichia coli. 25430540 9 59 theme methanolic 1754:1763 arg1 extract 1765:1771 E. triplinerve methanolic extract 1739:1771 E. triplinerve methanolic extract 1739:1771 DISCUSSION AND CONCLUSION Data showed that non-polar fractions of E. triplinerve methanolic extract has better antimicrobial activity and most likely depends on the presence of several compounds, such as depsidones, coumarins, saponins, and triterpenes on crude extract. 25430540 7 60 theme MIC 1410:1412 arg1 values 1414:1419 lower MIC values 1404:1419 lower MIC values of 62 and 75 µg/mL against Enterococcus faecalis and Staphylococcus aureus, respectively 1404:1508 The methanol extract of leaves presented the highest content of coumarins and lower MIC values of 62 and 75 µg/mL against Enterococcus faecalis and Staphylococcus aureus, respectively. 25430540 5 61 theme antimicrobial 910:922 arg1 activity 924:931 The antimicrobial activity 906:931 The antimicrobial activity of the different extracts 906:957 The antimicrobial activity of the different extracts was performed by microdilution assay and the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values were reported. 25430540 4 62 theme standard 885:892 arg1 techniques 894:903 standard techniques 885:903 standard techniques 885:903 The major chemical groups, saponins, reducing sugars, alkaloids, steroids, triterpenoids, phenols, tannins, flavonoids, and others were screened by standard techniques. 25430540 10 63 theme antibacterial 2000:2012 arg1 agents 2014:2019 new antibacterial agents 1996:2019 new antibacterial agents 1996:2019 The results can be exploited largely in research of new antibacterial agents. 25430540 5 64 theme bactericidal 1055:1066 arg1 concentration 1068:1080 minimum bactericidal concentration 1047:1080 minimum bactericidal concentration (MBC) 1047:1086 The antimicrobial activity of the different extracts was performed by microdilution assay and the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values were reported. 25430540 5 64 theme bactericidal 1055:1066 arg1 MBC 1083:1085 MBC 1083:1085 MBC 1083:1085 The antimicrobial activity of the different extracts was performed by microdilution assay and the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values were reported. 25430540 3 65 theme plant 627:631 arg1 parts 618:622 all parts 614:622 all parts of plant 614:631 MATERIALS AND METHODS Extracts were obtained by maceration of all parts of plant, and subjected to bioassay-guided fractionation of methanol extract by partition column chromatography. 25430540 3 66 dep MATERIALS 552:560 arg1 Extracts 574:581 Extracts 574:581 Extracts 574:581 MATERIALS AND METHODS Extracts were obtained by maceration of all parts of plant, and subjected to bioassay-guided fractionation of methanol extract by partition column chromatography. 25430540 9 67 from coumarins 1889:1897 arg1 extract 1935:1941 crude extract 1929:1941 crude extract 1929:1941 DISCUSSION AND CONCLUSION Data showed that non-polar fractions of E. triplinerve methanolic extract has better antimicrobial activity and most likely depends on the presence of several compounds, such as depsidones, coumarins, saponins, and triterpenes on crude extract. 25430540 9 68 theme antimicrobial 1784:1796 arg1 activity 1798:1805 better antimicrobial activity 1777:1805 better antimicrobial activity 1777:1805 DISCUSSION AND CONCLUSION Data showed that non-polar fractions of E. triplinerve methanolic extract has better antimicrobial activity and most likely depends on the presence of several compounds, such as depsidones, coumarins, saponins, and triterpenes on crude extract. 25430540 1 69 used used 180:183 arg2 Asteraceae 130:139 Asteraceae 130:139 Asteraceae 130:139 CONTEXT Eupatorium triplinerve Vahl (Asteraceae), popularly known as Japana, is widely used in folk medicine, due its analgesic, anticoagulant, antianorexic, antiparasitic, anthelmintic, sedative, antifungal, and antibacterial properties. 25430540 1 69 used used 180:183 arg2 Vahl 124:127 CONTEXT Eupatorium triplinerve Vahl 93:127 CONTEXT Eupatorium triplinerve Vahl (Asteraceae) 93:140 CONTEXT Eupatorium triplinerve Vahl (Asteraceae), popularly known as Japana, is widely used in folk medicine, due its analgesic, anticoagulant, antianorexic, antiparasitic, anthelmintic, sedative, antifungal, and antibacterial properties. 25430540 4 70 theme major 741:745 arg1 triterpenoids 812:824 triterpenoids 812:824 triterpenoids 812:824 The major chemical groups, saponins, reducing sugars, alkaloids, steroids, triterpenoids, phenols, tannins, flavonoids, and others were screened by standard techniques. 25430540 4 70 theme major 741:745 arg1 flavonoids 845:854 flavonoids 845:854 flavonoids 845:854 The major chemical groups, saponins, reducing sugars, alkaloids, steroids, triterpenoids, phenols, tannins, flavonoids, and others were screened by standard techniques. 25430540 4 70 theme major 741:745 arg1 sugars 783:788 reducing sugars 774:788 reducing sugars 774:788 The major chemical groups, saponins, reducing sugars, alkaloids, steroids, triterpenoids, phenols, tannins, flavonoids, and others were screened by standard techniques. 25430540 4 70 theme major 741:745 arg1 alkaloids 791:799 alkaloids 791:799 alkaloids 791:799 The major chemical groups, saponins, reducing sugars, alkaloids, steroids, triterpenoids, phenols, tannins, flavonoids, and others were screened by standard techniques. 25430540 4 70 theme major 741:745 arg1 phenols 827:833 phenols 827:833 phenols 827:833 The major chemical groups, saponins, reducing sugars, alkaloids, steroids, triterpenoids, phenols, tannins, flavonoids, and others were screened by standard techniques. 25430540 4 70 theme major 741:745 arg1 groups 756:761 The major chemical groups 737:761 The major chemical groups 737:761 The major chemical groups, saponins, reducing sugars, alkaloids, steroids, triterpenoids, phenols, tannins, flavonoids, and others were screened by standard techniques. 25430540 4 70 theme major 741:745 arg1 others 861:866 others 861:866 others 861:866 The major chemical groups, saponins, reducing sugars, alkaloids, steroids, triterpenoids, phenols, tannins, flavonoids, and others were screened by standard techniques. 25430540 4 70 theme major 741:745 arg1 tannins 836:842 tannins 836:842 tannins 836:842 The major chemical groups, saponins, reducing sugars, alkaloids, steroids, triterpenoids, phenols, tannins, flavonoids, and others were screened by standard techniques. 25430540 4 70 theme major 741:745 arg1 saponins 764:771 saponins 764:771 saponins 764:771 The major chemical groups, saponins, reducing sugars, alkaloids, steroids, triterpenoids, phenols, tannins, flavonoids, and others were screened by standard techniques. 25430540 4 70 theme major 741:745 arg1 steroids 802:809 steroids 802:809 steroids 802:809 The major chemical groups, saponins, reducing sugars, alkaloids, steroids, triterpenoids, phenols, tannins, flavonoids, and others were screened by standard techniques. 25430540 3 71 theme parts 618:622 arg1 maceration 600:609 maceration 600:609 maceration of all parts of plant 600:631 MATERIALS AND METHODS Extracts were obtained by maceration of all parts of plant, and subjected to bioassay-guided fractionation of methanol extract by partition column chromatography. 25430540 7 72 theme highest 1371:1377 arg1 content 1379:1385 the highest content 1367:1385 the highest content of coumarins and lower MIC values of 62 and 75 µg/mL against Enterococcus faecalis and Staphylococcus aureus, respectively 1367:1508 The methanol extract of leaves presented the highest content of coumarins and lower MIC values of 62 and 75 µg/mL against Enterococcus faecalis and Staphylococcus aureus, respectively. 25430540 8 73 theme non-polar 1528:1536 arg1 fractions 1538:1546 its non-polar fractions 1524:1546 its non-polar fractions 1524:1546 In addition, its non-polar fractions showed antimicrobial activity with MIC ranging from 16 to 125 µg/mL against Gram-negative bacteria, mainly Escherichia coli. 25430540 2 74 theme highest 519:525 arg1 potential 541:549 the highest antimicrobial potential 515:549 the highest antimicrobial potential 515:549 OBJECTIVE The present study evaluated the chemical composition and antimicrobial activity of E. triplinerve extracts from different parts of the plant and identified the extract with the highest antimicrobial potential. 25430540 4 75 theme reducing 774:781 arg1 sugars 783:788 reducing sugars 774:788 reducing sugars 774:788 The major chemical groups, saponins, reducing sugars, alkaloids, steroids, triterpenoids, phenols, tannins, flavonoids, and others were screened by standard techniques. 25430540 4 75 theme reducing 774:781 arg1 groups 756:761 The major chemical groups 737:761 The major chemical groups 737:761 The major chemical groups, saponins, reducing sugars, alkaloids, steroids, triterpenoids, phenols, tannins, flavonoids, and others were screened by standard techniques. 25430540 7 76 theme leaves 1350:1355 arg1 extract 1339:1345 The methanol extract 1326:1345 The methanol extract of leaves 1326:1355 The methanol extract of leaves presented the highest content of coumarins and lower MIC values of 62 and 75 µg/mL against Enterococcus faecalis and Staphylococcus aureus, respectively. 25430540 0 77 theme bioassay-guided 14:28 arg1 fractionation 30:42 Antimicrobial bioassay-guided fractionation 0:42 Antimicrobial bioassay-guided fractionation of a methanol extract of Eupatorium 0:78 Antimicrobial bioassay-guided fractionation of a methanol extract of Eupatorium triplinerve. 25430540 5 78 theme different 940:948 arg1 extracts 950:957 the different extracts 936:957 the different extracts 936:957 The antimicrobial activity of the different extracts was performed by microdilution assay and the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values were reported. 25430540 9 79 theme several 1850:1856 arg1 compounds 1858:1866 several compounds 1850:1866 several compounds 1850:1866 DISCUSSION AND CONCLUSION Data showed that non-polar fractions of E. triplinerve methanolic extract has better antimicrobial activity and most likely depends on the presence of several compounds, such as depsidones, coumarins, saponins, and triterpenes on crude extract. 25430540 9 79 theme several 1850:1856 arg1 saponins 1900:1907 saponins 1900:1907 saponins 1900:1907 DISCUSSION AND CONCLUSION Data showed that non-polar fractions of E. triplinerve methanolic extract has better antimicrobial activity and most likely depends on the presence of several compounds, such as depsidones, coumarins, saponins, and triterpenes on crude extract. 25430540 9 79 theme several 1850:1856 arg1 coumarins 1889:1897 coumarins 1889:1897 coumarins 1889:1897 DISCUSSION AND CONCLUSION Data showed that non-polar fractions of E. triplinerve methanolic extract has better antimicrobial activity and most likely depends on the presence of several compounds, such as depsidones, coumarins, saponins, and triterpenes on crude extract. 25430540 9 79 theme several 1850:1856 arg1 depsidones 1877:1886 depsidones 1877:1886 depsidones 1877:1886 DISCUSSION AND CONCLUSION Data showed that non-polar fractions of E. triplinerve methanolic extract has better antimicrobial activity and most likely depends on the presence of several compounds, such as depsidones, coumarins, saponins, and triterpenes on crude extract. 25430540 9 79 theme several 1850:1856 arg1 triterpenes 1914:1924 triterpenes 1914:1924 triterpenes 1914:1924 DISCUSSION AND CONCLUSION Data showed that non-polar fractions of E. triplinerve methanolic extract has better antimicrobial activity and most likely depends on the presence of several compounds, such as depsidones, coumarins, saponins, and triterpenes on crude extract. 25430540 2 80 theme triplinerve 428:438 arg1 extracts 440:447 E. triplinerve extracts 425:447 E. triplinerve extracts 425:447 OBJECTIVE The present study evaluated the chemical composition and antimicrobial activity of E. triplinerve extracts from different parts of the plant and identified the extract with the highest antimicrobial potential. 25430540 0 81 theme methanol 49:56 arg1 extract 58:64 a methanol extract 47:64 a methanol extract of Eupatorium 47:78 Antimicrobial bioassay-guided fractionation of a methanol extract of Eupatorium triplinerve. 25430540 2 82 theme antimicrobial 399:411 arg1 activity 413:420 antimicrobial activity 399:420 antimicrobial activity 399:420 OBJECTIVE The present study evaluated the chemical composition and antimicrobial activity of E. triplinerve extracts from different parts of the plant and identified the extract with the highest antimicrobial potential. 25430540 6 83 theme extract 1160:1166 arg1 screening 1132:1140 RESULTS Phytochemical screening 1110:1140 RESULTS Phytochemical screening of hydroalcoholic extract from all parts of E. triplinerve 1110:1199 RESULTS Phytochemical screening of hydroalcoholic extract from all parts of E. triplinerve identified mainly steroids, coumarins, alkaloids, saponins, tannins, depsides and absence of polysaccharides and flavonoids. 25430540 3 84 theme methanol 684:691 arg1 extract 693:699 methanol extract 684:699 methanol extract 684:699 MATERIALS AND METHODS Extracts were obtained by maceration of all parts of plant, and subjected to bioassay-guided fractionation of methanol extract by partition column chromatography. 25430540 8 85 theme Gram-negative 1624:1636 arg1 bacteria 1638:1645 Gram-negative bacteria 1624:1645 Gram-negative bacteria 1624:1645 In addition, its non-polar fractions showed antimicrobial activity with MIC ranging from 16 to 125 µg/mL against Gram-negative bacteria, mainly Escherichia coli. 25430540 8 85 theme Gram-negative 1624:1636 arg1 coli 1667:1670 Escherichia coli 1655:1670 Escherichia coli 1655:1670 In addition, its non-polar fractions showed antimicrobial activity with MIC ranging from 16 to 125 µg/mL against Gram-negative bacteria, mainly Escherichia coli. 25430540 5 86 theme inhibitory 1012:1021 arg1 MIC 1038:1040 MIC 1038:1040 MIC 1038:1040 The antimicrobial activity of the different extracts was performed by microdilution assay and the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values were reported. 25430540 5 86 theme inhibitory 1012:1021 arg1 concentration 1023:1035 minimum inhibitory concentration 1004:1035 minimum inhibitory concentration (MIC) 1004:1041 The antimicrobial activity of the different extracts was performed by microdilution assay and the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values were reported. 25430540 6 87 theme Phytochemical 1118:1130 arg1 screening 1132:1140 RESULTS Phytochemical screening 1110:1140 RESULTS Phytochemical screening of hydroalcoholic extract from all parts of E. triplinerve 1110:1199 RESULTS Phytochemical screening of hydroalcoholic extract from all parts of E. triplinerve identified mainly steroids, coumarins, alkaloids, saponins, tannins, depsides and absence of polysaccharides and flavonoids. 25430540 3 88 theme column 714:719 arg1 chromatography 721:734 partition column chromatography 704:734 partition column chromatography 704:734 MATERIALS AND METHODS Extracts were obtained by maceration of all parts of plant, and subjected to bioassay-guided fractionation of methanol extract by partition column chromatography. 25430540 2 89 dep composition 383:393 arg1 the 370:372 the 370:372 the 370:372 OBJECTIVE The present study evaluated the chemical composition and antimicrobial activity of E. triplinerve extracts from different parts of the plant and identified the extract with the highest antimicrobial potential. 25988123 8 0 theme acid-restricted 1156:1170 arg1 medium 1172:1177 amino acid-restricted medium 1150:1177 amino acid-restricted medium 1150:1177 In amino acid-restricted medium, fermentation leading to acetic acid formation was dominant at the beginning of growth (up to 24 h), followed by increased lactic acid production, and mainly propionic and succinic acids were produced at the end of fermentation. 25988123 2 1 theme B. 347:348 arg1 thetaiotaomicron 350:365 B. thetaiotaomicron 347:365 B. thetaiotaomicron 347:365 A model of cross-talk between the metabolism of amino acids and fructans in B. thetaiotaomicron was proposed. 25988123 1 2 theme polysaccharides 254:268 arg1 catabolism 232:241 catabolism 232:241 catabolism of various polysaccharides 232:268 Bacteroides thetaiotaomicron is commonly found in the human colon and stabilizes its ecosystem by catabolism of various polysaccharides. 25988123 3 3 theme isothermal 552:561 arg1 microcalorimeter 563:578 an isothermal microcalorimeter 549:578 an isothermal microcalorimeter 549:578 The growth of B. thetaiotaomicron DSM 2079 in two defined media containing mineral salts and vitamins, and supplemented with either 20 or 2 amino acids, was studied in an isothermal microcalorimeter. 25988123 2 4 theme cross-talk 282:291 arg1 model 273:277 A model 271:277 A model of cross-talk between the metabolism of amino acids and fructans in B. thetaiotaomicron 271:365 A model of cross-talk between the metabolism of amino acids and fructans in B. thetaiotaomicron was proposed. 25988123 13 5 theme colon 2095:2099 arg1 microbiota 2101:2110 modifying colon microbiota 2085:2110 modifying colon microbiota 2085:2110 The effect of levan on balancing or modifying colon microbiota will be studied in further experiments. 25988123 6 6 theme amino 903:907 arg1 acids 909:913 amino acids 903:913 amino acids 903:913 A surplus of amino acids reduced the consumption of longer oligosaccharides (degree of polymerization > 3). 25988123 7 7 located detected 1023:1030 arg1 medium 1064:1069 the carbohydrate free medium 1042:1069 the carbohydrate free medium containing amino acids 1042:1092 Bacterial growth was not detected either in the carbohydrate free medium containing amino acids or in the medium with inulin as a sole carbohydrate. 25988123 7 7 located detected 1023:1030 arg2 growth 1008:1013 Bacterial growth 998:1013 Bacterial growth 998:1013 Bacterial growth was not detected either in the carbohydrate free medium containing amino acids or in the medium with inulin as a sole carbohydrate. 25988123 3 8 theme amino 521:525 arg1 acids 527:531 either 20 or 2 amino acids 506:531 acids 527:531 The growth of B. thetaiotaomicron DSM 2079 in two defined media containing mineral salts and vitamins, and supplemented with either 20 or 2 amino acids, was studied in an isothermal microcalorimeter. 25988123 8 9 theme acetic 1204:1209 arg1 formation 1216:1224 acetic acid formation 1204:1224 acetic acid formation 1204:1224 In amino acid-restricted medium, fermentation leading to acetic acid formation was dominant at the beginning of growth (up to 24 h), followed by increased lactic acid production, and mainly propionic and succinic acids were produced at the end of fermentation. 25988123 9 10 dep 17 mmol/gDW 1566:1576 arg1 to 1563:1564 to 1563:1564 to 1563:1564 In the medium supplemented with 20 amino acids, the highest production of d-lactate (82 ± 33 mmol/gDW) occurred in parallel with extensive consumption (up to 17 mmol/gDW) of amino acids, especially Ser, Thr, and Asp. 25988123 1 11 theme human 188:192 arg1 colon 194:198 the human colon 184:198 the human colon 184:198 Bacteroides thetaiotaomicron is commonly found in the human colon and stabilizes its ecosystem by catabolism of various polysaccharides. 25988123 11 12 theme acids 1800:1804 arg1 influence 1781:1789 the influence 1777:1789 the influence of amino acids on fructan metabolism in B. thetaiotaomicron 1777:1849 The study revealed the influence of amino acids on fructan metabolism in B. thetaiotaomicron and showed that defined growth media are invaluable in elucidating quantitative metabolic profiles of the bacteria. 25988123 10 13 located observed 1659:1666 arg2 production 1629:1638 The production 1625:1638 The production of Ala and Glu 1625:1653 The production of Ala and Glu was observed at growth on all substrates, and the production was enhanced under amino acid deficiency. 25988123 10 13 located observed 1659:1666 arg1 growth 1671:1676 growth 1671:1676 growth on all substrates 1671:1694 The production of Ala and Glu was observed at growth on all substrates, and the production was enhanced under amino acid deficiency. 25988123 13 14 theme levan 2063:2067 arg1 effect 2053:2058 The effect 2049:2058 The effect of levan on balancing or modifying colon microbiota 2049:2110 The effect of levan on balancing or modifying colon microbiota will be studied in further experiments. 25988123 10 15 theme amino 1735:1739 arg1 deficiency 1746:1755 amino acid deficiency 1735:1755 amino acid deficiency 1735:1755 The production of Ala and Glu was observed at growth on all substrates, and the production was enhanced under amino acid deficiency. 25988123 12 16 theme degradable 2003:2012 arg1 Levan 1967:1971 Levan 1967:1971 Levan 1967:1971 Levan was shown to act as an easily degradable substrate for B. thetaiotaomicron. 25988123 12 16 theme degradable 2003:2012 arg1 substrate 2014:2022 an easily degradable substrate 1993:2022 an easily degradable substrate for B. thetaiotaomicron 1993:2046 Levan was shown to act as an easily degradable substrate for B. thetaiotaomicron. 25988123 9 17 with parallel 1523:1530 arg1 consumption 1547:1557 extensive consumption 1537:1557 extensive consumption (up to 17 mmol/gDW) of amino acids, especially Ser, Thr, and Asp 1537:1622 In the medium supplemented with 20 amino acids, the highest production of d-lactate (82 ± 33 mmol/gDW) occurred in parallel with extensive consumption (up to 17 mmol/gDW) of amino acids, especially Ser, Thr, and Asp. 25988123 6 18 theme longer 942:947 arg1 oligosaccharides 949:964 longer oligosaccharides 942:964 longer oligosaccharides (degree of polymerization > 3) 942:995 A surplus of amino acids reduced the consumption of longer oligosaccharides (degree of polymerization > 3). 25988123 8 19 theme increased 1292:1300 arg1 production 1314:1323 increased lactic acid production 1292:1323 increased lactic acid production 1292:1323 In amino acid-restricted medium, fermentation leading to acetic acid formation was dominant at the beginning of growth (up to 24 h), followed by increased lactic acid production, and mainly propionic and succinic acids were produced at the end of fermentation. 25988123 7 20 theme free 1059:1062 arg1 medium 1064:1069 the carbohydrate free medium 1042:1069 the carbohydrate free medium containing amino acids 1042:1092 Bacterial growth was not detected either in the carbohydrate free medium containing amino acids or in the medium with inulin as a sole carbohydrate. 25988123 11 21 theme metabolic 1931:1939 arg1 profiles 1941:1948 quantitative metabolic profiles 1918:1948 quantitative metabolic profiles of the bacteria 1918:1964 The study revealed the influence of amino acids on fructan metabolism in B. thetaiotaomicron and showed that defined growth media are invaluable in elucidating quantitative metabolic profiles of the bacteria. 25988123 9 22 theme d-lactate 1482:1490 arg1 production 1468:1477 the highest production 1456:1477 the highest production of d-lactate (82 ± 33 mmol/gDW) 1456:1509 In the medium supplemented with 20 amino acids, the highest production of d-lactate (82 ± 33 mmol/gDW) occurred in parallel with extensive consumption (up to 17 mmol/gDW) of amino acids, especially Ser, Thr, and Asp. 25988123 8 23 theme acid 1309:1312 arg1 production 1314:1323 increased lactic acid production 1292:1323 increased lactic acid production 1292:1323 In amino acid-restricted medium, fermentation leading to acetic acid formation was dominant at the beginning of growth (up to 24 h), followed by increased lactic acid production, and mainly propionic and succinic acids were produced at the end of fermentation. 25988123 11 24 theme B. 1831:1832 arg1 thetaiotaomicron 1834:1849 B. thetaiotaomicron 1831:1849 B. thetaiotaomicron 1831:1849 The study revealed the influence of amino acids on fructan metabolism in B. thetaiotaomicron and showed that defined growth media are invaluable in elucidating quantitative metabolic profiles of the bacteria. 25988123 7 25 theme Bacterial 998:1006 arg1 growth 1008:1013 Bacterial growth 998:1013 Bacterial growth 998:1013 Bacterial growth was not detected either in the carbohydrate free medium containing amino acids or in the medium with inulin as a sole carbohydrate. 25988123 2 26 from metabolism 305:314 arg1 thetaiotaomicron 350:365 B. thetaiotaomicron 347:365 B. thetaiotaomicron 347:365 A model of cross-talk between the metabolism of amino acids and fructans in B. thetaiotaomicron was proposed. 25988123 9 27 dep consumption 1547:1557 arg1 17 mmol/gDW 1566:1576 17 mmol/gDW 1566:1576 17 mmol/gDW 1566:1576 In the medium supplemented with 20 amino acids, the highest production of d-lactate (82 ± 33 mmol/gDW) occurred in parallel with extensive consumption (up to 17 mmol/gDW) of amino acids, especially Ser, Thr, and Asp. 25988123 11 28 theme bacteria 1957:1964 arg1 profiles 1941:1948 quantitative metabolic profiles 1918:1948 quantitative metabolic profiles of the bacteria 1918:1964 The study revealed the influence of amino acids on fructan metabolism in B. thetaiotaomicron and showed that defined growth media are invaluable in elucidating quantitative metabolic profiles of the bacteria. 25988123 8 29 dep 24 h 1273:1276 arg1 to 1270:1271 to 1270:1271 to 1270:1271 In amino acid-restricted medium, fermentation leading to acetic acid formation was dominant at the beginning of growth (up to 24 h), followed by increased lactic acid production, and mainly propionic and succinic acids were produced at the end of fermentation. 25988123 3 30 theme defined 431:437 arg1 media 439:443 two defined media 427:443 two defined media containing mineral salts and vitamins, and supplemented with either 20 or 2 amino acids 427:531 The growth of B. thetaiotaomicron DSM 2079 in two defined media containing mineral salts and vitamins, and supplemented with either 20 or 2 amino acids, was studied in an isothermal microcalorimeter. 25988123 3 31 from growth 385:390 arg1 media 439:443 two defined media 427:443 two defined media containing mineral salts and vitamins, and supplemented with either 20 or 2 amino acids 427:531 The growth of B. thetaiotaomicron DSM 2079 in two defined media containing mineral salts and vitamins, and supplemented with either 20 or 2 amino acids, was studied in an isothermal microcalorimeter. 25988123 9 32 theme extensive 1537:1545 arg1 consumption 1547:1557 extensive consumption 1537:1557 extensive consumption (up to 17 mmol/gDW) of amino acids, especially Ser, Thr, and Asp 1537:1622 In the medium supplemented with 20 amino acids, the highest production of d-lactate (82 ± 33 mmol/gDW) occurred in parallel with extensive consumption (up to 17 mmol/gDW) of amino acids, especially Ser, Thr, and Asp. 25988123 4 33 theme different 734:742 arg1 composition 744:754 different composition 734:754 different composition 734:754 The polyfructans inulin (from chicory) and levan (synthesized using levansucrase from Pseudomonas syringae), two fructooligosaccharide preparations with different composition, sucrose and fructose were tested as substrates. 25988123 5 34 theme calorimetric 809:820 arg1 specific 855:862 specific 855:862 specific 855:862 The calorimetric power-time curves were substrate specific and typically multiauxic. 25988123 5 34 theme calorimetric 809:820 arg1 curves 833:838 The calorimetric power-time curves 805:838 The calorimetric power-time curves 805:838 The calorimetric power-time curves were substrate specific and typically multiauxic. 25988123 0 35 theme Fructans 15:22 arg1 Degradation 0:10 Degradation 0:10 Degradation of Fructans 0:22 Degradation of Fructans and Production of Propionic Acid by Bacteroides thetaiotaomicron are Enhanced by the Shortage of Amino Acids. 25988123 0 35 theme Fructans 15:22 arg1 Production 28:37 Production 28:37 Production of Propionic Acid by Bacteroides thetaiotaomicron 28:87 Degradation of Fructans and Production of Propionic Acid by Bacteroides thetaiotaomicron are Enhanced by the Shortage of Amino Acids. 25988123 3 36 theme DSM 415:417 arg1 2079 419:422 B. thetaiotaomicron DSM 2079 395:422 B. thetaiotaomicron DSM 2079 395:422 The growth of B. thetaiotaomicron DSM 2079 in two defined media containing mineral salts and vitamins, and supplemented with either 20 or 2 amino acids, was studied in an isothermal microcalorimeter. 25988123 8 37 dep dominant 1230:1237 arg1 24 h 1273:1276 24 h 1273:1276 24 h 1273:1276 In amino acid-restricted medium, fermentation leading to acetic acid formation was dominant at the beginning of growth (up to 24 h), followed by increased lactic acid production, and mainly propionic and succinic acids were produced at the end of fermentation. 25988123 8 37 dep dominant 1230:1237 arg1 followed 1280:1287 followed 1280:1287 followed by increased lactic acid production 1280:1323 In amino acid-restricted medium, fermentation leading to acetic acid formation was dominant at the beginning of growth (up to 24 h), followed by increased lactic acid production, and mainly propionic and succinic acids were produced at the end of fermentation. 25988123 3 38 theme B. 395:396 arg1 2079 419:422 B. thetaiotaomicron DSM 2079 395:422 B. thetaiotaomicron DSM 2079 395:422 The growth of B. thetaiotaomicron DSM 2079 in two defined media containing mineral salts and vitamins, and supplemented with either 20 or 2 amino acids, was studied in an isothermal microcalorimeter. 25988123 10 39 theme Glu 1651:1653 arg1 production 1629:1638 The production 1625:1638 The production of Ala and Glu 1625:1653 The production of Ala and Glu was observed at growth on all substrates, and the production was enhanced under amino acid deficiency. 25988123 0 40 theme Propionic 42:50 arg1 Acid 52:55 Propionic Acid 42:55 Propionic Acid 42:55 Degradation of Fructans and Production of Propionic Acid by Bacteroides thetaiotaomicron are Enhanced by the Shortage of Amino Acids. 25988123 9 41 theme amino 1582:1586 arg1 Asp 1620:1622 Asp 1620:1622 Asp 1620:1622 In the medium supplemented with 20 amino acids, the highest production of d-lactate (82 ± 33 mmol/gDW) occurred in parallel with extensive consumption (up to 17 mmol/gDW) of amino acids, especially Ser, Thr, and Asp. 25988123 9 41 theme amino 1582:1586 arg1 Thr 1611:1613 Thr 1611:1613 Thr 1611:1613 In the medium supplemented with 20 amino acids, the highest production of d-lactate (82 ± 33 mmol/gDW) occurred in parallel with extensive consumption (up to 17 mmol/gDW) of amino acids, especially Ser, Thr, and Asp. 25988123 9 41 theme amino 1582:1586 arg1 acids 1588:1592 amino acids 1582:1592 amino acids 1582:1592 In the medium supplemented with 20 amino acids, the highest production of d-lactate (82 ± 33 mmol/gDW) occurred in parallel with extensive consumption (up to 17 mmol/gDW) of amino acids, especially Ser, Thr, and Asp. 25988123 9 41 theme amino 1582:1586 arg1 Ser 1606:1608 Ser 1606:1608 Ser 1606:1608 In the medium supplemented with 20 amino acids, the highest production of d-lactate (82 ± 33 mmol/gDW) occurred in parallel with extensive consumption (up to 17 mmol/gDW) of amino acids, especially Ser, Thr, and Asp. 25988123 7 42 with medium 1104:1109 arg1 inulin 1116:1121 inulin 1116:1121 inulin 1116:1121 Bacterial growth was not detected either in the carbohydrate free medium containing amino acids or in the medium with inulin as a sole carbohydrate. 25988123 10 43 theme Ala 1643:1645 arg1 production 1629:1638 The production 1625:1638 The production of Ala and Glu 1625:1653 The production of Ala and Glu was observed at growth on all substrates, and the production was enhanced under amino acid deficiency. 25988123 7 44 theme sole 1128:1131 arg1 carbohydrate 1133:1144 a sole carbohydrate 1126:1144 a sole carbohydrate 1126:1144 Bacterial growth was not detected either in the carbohydrate free medium containing amino acids or in the medium with inulin as a sole carbohydrate. 25988123 11 45 theme amino 1794:1798 arg1 acids 1800:1804 amino acids 1794:1804 amino acids 1794:1804 The study revealed the influence of amino acids on fructan metabolism in B. thetaiotaomicron and showed that defined growth media are invaluable in elucidating quantitative metabolic profiles of the bacteria. 25988123 4 46 from syringae 679:686 arg1 levansucrase 649:660 levansucrase 649:660 levansucrase from Pseudomonas syringae 649:686 The polyfructans inulin (from chicory) and levan (synthesized using levansucrase from Pseudomonas syringae), two fructooligosaccharide preparations with different composition, sucrose and fructose were tested as substrates. 25988123 1 47 theme various 246:252 arg1 polysaccharides 254:268 various polysaccharides 246:268 various polysaccharides 246:268 Bacteroides thetaiotaomicron is commonly found in the human colon and stabilizes its ecosystem by catabolism of various polysaccharides. 25988123 8 48 theme amino 1150:1154 arg1 medium 1172:1177 amino acid-restricted medium 1150:1177 amino acid-restricted medium 1150:1177 In amino acid-restricted medium, fermentation leading to acetic acid formation was dominant at the beginning of growth (up to 24 h), followed by increased lactic acid production, and mainly propionic and succinic acids were produced at the end of fermentation. 25988123 13 49 theme modifying 2085:2093 arg1 microbiota 2101:2110 modifying colon microbiota 2085:2110 modifying colon microbiota 2085:2110 The effect of levan on balancing or modifying colon microbiota will be studied in further experiments. 25988123 6 50 theme acids 909:913 arg1 surplus 892:898 A surplus 890:898 A surplus of amino acids 890:913 A surplus of amino acids reduced the consumption of longer oligosaccharides (degree of polymerization > 3). 25988123 13 51 from effect 2053:2058 arg1 balancing 2072:2080 balancing 2072:2080 balancing 2072:2080 The effect of levan on balancing or modifying colon microbiota will be studied in further experiments. 25988123 13 51 from effect 2053:2058 arg1 microbiota 2101:2110 modifying colon microbiota 2085:2110 modifying colon microbiota 2085:2110 The effect of levan on balancing or modifying colon microbiota will be studied in further experiments. 25988123 3 52 theme thetaiotaomicron 398:413 arg1 2079 419:422 B. thetaiotaomicron DSM 2079 395:422 B. thetaiotaomicron DSM 2079 395:422 The growth of B. thetaiotaomicron DSM 2079 in two defined media containing mineral salts and vitamins, and supplemented with either 20 or 2 amino acids, was studied in an isothermal microcalorimeter. 25988123 8 53 from dominant 1230:1237 arg1 medium 1172:1177 amino acid-restricted medium 1150:1177 amino acid-restricted medium 1150:1177 In amino acid-restricted medium, fermentation leading to acetic acid formation was dominant at the beginning of growth (up to 24 h), followed by increased lactic acid production, and mainly propionic and succinic acids were produced at the end of fermentation. 25988123 2 54 theme amino 319:323 arg1 acids 325:329 amino acids 319:329 amino acids 319:329 A model of cross-talk between the metabolism of amino acids and fructans in B. thetaiotaomicron was proposed. 25988123 10 55 from growth 1671:1676 arg1 substrates 1685:1694 all substrates 1681:1694 all substrates 1681:1694 The production of Ala and Glu was observed at growth on all substrates, and the production was enhanced under amino acid deficiency. 25988123 8 56 theme growth 1259:1264 arg1 beginning 1246:1254 the beginning 1242:1254 the beginning of growth 1242:1264 In amino acid-restricted medium, fermentation leading to acetic acid formation was dominant at the beginning of growth (up to 24 h), followed by increased lactic acid production, and mainly propionic and succinic acids were produced at the end of fermentation. 25988123 0 57 theme Amino 121:125 arg1 Acids 127:131 Amino Acids 121:131 Amino Acids 121:131 Degradation of Fructans and Production of Propionic Acid by Bacteroides thetaiotaomicron are Enhanced by the Shortage of Amino Acids. 25988123 3 58 dep media 439:443 arg1 supplemented 488:499 supplemented 488:499 supplemented with either 20 or 2 amino acids 488:531 The growth of B. thetaiotaomicron DSM 2079 in two defined media containing mineral salts and vitamins, and supplemented with either 20 or 2 amino acids, was studied in an isothermal microcalorimeter. 25988123 3 58 dep media 439:443 arg1 containing 445:454 containing 445:454 containing mineral salts and vitamins 445:481 The growth of B. thetaiotaomicron DSM 2079 in two defined media containing mineral salts and vitamins, and supplemented with either 20 or 2 amino acids, was studied in an isothermal microcalorimeter. 25988123 9 59 theme amino 1443:1447 arg1 acids 1449:1453 20 amino acids 1440:1453 20 amino acids 1440:1453 In the medium supplemented with 20 amino acids, the highest production of d-lactate (82 ± 33 mmol/gDW) occurred in parallel with extensive consumption (up to 17 mmol/gDW) of amino acids, especially Ser, Thr, and Asp. 25988123 8 60 theme acid 1211:1214 arg1 formation 1216:1224 acetic acid formation 1204:1224 acetic acid formation 1204:1224 In amino acid-restricted medium, fermentation leading to acetic acid formation was dominant at the beginning of growth (up to 24 h), followed by increased lactic acid production, and mainly propionic and succinic acids were produced at the end of fermentation. 25988123 6 61 theme polymerization > 3 977:994 arg1 degree 967:972 degree 967:972 degree of polymerization > 3 967:994 A surplus of amino acids reduced the consumption of longer oligosaccharides (degree of polymerization > 3). 25988123 6 62 dep oligosaccharides 949:964 arg1 degree 967:972 degree 967:972 degree of polymerization > 3 967:994 A surplus of amino acids reduced the consumption of longer oligosaccharides (degree of polymerization > 3). 25988123 12 63 theme B. 2028:2029 arg1 thetaiotaomicron 2031:2046 B. thetaiotaomicron 2028:2046 B. thetaiotaomicron 2028:2046 Levan was shown to act as an easily degradable substrate for B. thetaiotaomicron. 25988123 7 64 theme amino 1082:1086 arg1 acids 1088:1092 amino acids 1082:1092 amino acids 1082:1092 Bacterial growth was not detected either in the carbohydrate free medium containing amino acids or in the medium with inulin as a sole carbohydrate. 25988123 1 65 located found 175:179 arg2 thetaiotaomicron 146:161 Bacteroides thetaiotaomicron 134:161 Bacteroides thetaiotaomicron 134:161 Bacteroides thetaiotaomicron is commonly found in the human colon and stabilizes its ecosystem by catabolism of various polysaccharides. 25988123 1 65 located found 175:179 arg1 colon 194:198 the human colon 184:198 the human colon 184:198 Bacteroides thetaiotaomicron is commonly found in the human colon and stabilizes its ecosystem by catabolism of various polysaccharides. 25988123 10 66 theme acid 1741:1744 arg1 deficiency 1746:1755 amino acid deficiency 1735:1755 amino acid deficiency 1735:1755 The production of Ala and Glu was observed at growth on all substrates, and the production was enhanced under amino acid deficiency. 25988123 4 67 from chicory 611:617 arg1 inulin 598:603 inulin (from chicory) and levan (synthesized using levansucrase from Pseudomonas syringae) 598:687 inulin 598:603 The polyfructans inulin (from chicory) and levan (synthesized using levansucrase from Pseudomonas syringae), two fructooligosaccharide preparations with different composition, sucrose and fructose were tested as substrates. 25988123 4 67 from chicory 611:617 arg1 levan 624:628 inulin (from chicory) and levan (synthesized using levansucrase from Pseudomonas syringae) 598:687 levan 624:628 The polyfructans inulin (from chicory) and levan (synthesized using levansucrase from Pseudomonas syringae), two fructooligosaccharide preparations with different composition, sucrose and fructose were tested as substrates. 25988123 4 67 from chicory 611:617 arg1 polyfructans 585:596 The polyfructans inulin (from chicory) and levan (synthesized using levansucrase from Pseudomonas syringae), two fructooligosaccharide preparations with different composition 581:754 The polyfructans inulin (from chicory) and levan (synthesized using levansucrase from Pseudomonas syringae), two fructooligosaccharide preparations with different composition 581:754 The polyfructans inulin (from chicory) and levan (synthesized using levansucrase from Pseudomonas syringae), two fructooligosaccharide preparations with different composition, sucrose and fructose were tested as substrates. 25988123 4 67 from chicory 611:617 arg1 preparations 716:727 two fructooligosaccharide preparations 690:727 two fructooligosaccharide preparations with different composition 690:754 The polyfructans inulin (from chicory) and levan (synthesized using levansucrase from Pseudomonas syringae), two fructooligosaccharide preparations with different composition, sucrose and fructose were tested as substrates. 25988123 11 68 theme growth 1875:1880 arg1 media 1882:1886 defined growth media 1867:1886 defined growth media 1867:1886 The study revealed the influence of amino acids on fructan metabolism in B. thetaiotaomicron and showed that defined growth media are invaluable in elucidating quantitative metabolic profiles of the bacteria. 25988123 9 69 theme highest 1460:1466 arg1 production 1468:1477 the highest production 1456:1477 the highest production of d-lactate (82 ± 33 mmol/gDW) 1456:1509 In the medium supplemented with 20 amino acids, the highest production of d-lactate (82 ± 33 mmol/gDW) occurred in parallel with extensive consumption (up to 17 mmol/gDW) of amino acids, especially Ser, Thr, and Asp. 25988123 6 70 theme oligosaccharides 949:964 arg1 consumption 927:937 the consumption 923:937 the consumption of longer oligosaccharides (degree of polymerization > 3) 923:995 A surplus of amino acids reduced the consumption of longer oligosaccharides (degree of polymerization > 3). 25988123 7 71 theme carbohydrate 1046:1057 arg1 medium 1064:1069 the carbohydrate free medium 1042:1069 the carbohydrate free medium containing amino acids 1042:1092 Bacterial growth was not detected either in the carbohydrate free medium containing amino acids or in the medium with inulin as a sole carbohydrate. 25988123 11 72 theme quantitative 1918:1929 arg1 profiles 1941:1948 quantitative metabolic profiles 1918:1948 quantitative metabolic profiles of the bacteria 1918:1964 The study revealed the influence of amino acids on fructan metabolism in B. thetaiotaomicron and showed that defined growth media are invaluable in elucidating quantitative metabolic profiles of the bacteria. 25988123 8 73 from beginning 1246:1254 arg1 dominant 1230:1237 dominant 1230:1237 dominant 1230:1237 In amino acid-restricted medium, fermentation leading to acetic acid formation was dominant at the beginning of growth (up to 24 h), followed by increased lactic acid production, and mainly propionic and succinic acids were produced at the end of fermentation. 25988123 11 74 from metabolism 1817:1826 arg1 thetaiotaomicron 1834:1849 B. thetaiotaomicron 1831:1849 B. thetaiotaomicron 1831:1849 The study revealed the influence of amino acids on fructan metabolism in B. thetaiotaomicron and showed that defined growth media are invaluable in elucidating quantitative metabolic profiles of the bacteria. 25988123 4 75 theme fructooligosaccharide 694:714 arg1 inulin 598:603 inulin (from chicory) and levan (synthesized using levansucrase from Pseudomonas syringae) 598:687 inulin 598:603 The polyfructans inulin (from chicory) and levan (synthesized using levansucrase from Pseudomonas syringae), two fructooligosaccharide preparations with different composition, sucrose and fructose were tested as substrates. 25988123 4 75 theme fructooligosaccharide 694:714 arg1 preparations 716:727 two fructooligosaccharide preparations 690:727 two fructooligosaccharide preparations with different composition 690:754 The polyfructans inulin (from chicory) and levan (synthesized using levansucrase from Pseudomonas syringae), two fructooligosaccharide preparations with different composition, sucrose and fructose were tested as substrates. 25988123 0 76 theme Bacteroides 60:70 arg1 thetaiotaomicron 72:87 Bacteroides thetaiotaomicron 60:87 Bacteroides thetaiotaomicron 60:87 Degradation of Fructans and Production of Propionic Acid by Bacteroides thetaiotaomicron are Enhanced by the Shortage of Amino Acids. 25988123 4 77 dep polyfructans 585:596 arg1 inulin 598:603 inulin (from chicory) and levan (synthesized using levansucrase from Pseudomonas syringae) 598:687 inulin 598:603 The polyfructans inulin (from chicory) and levan (synthesized using levansucrase from Pseudomonas syringae), two fructooligosaccharide preparations with different composition, sucrose and fructose were tested as substrates. 25988123 4 77 dep polyfructans 585:596 arg1 levan 624:628 inulin (from chicory) and levan (synthesized using levansucrase from Pseudomonas syringae) 598:687 levan 624:628 The polyfructans inulin (from chicory) and levan (synthesized using levansucrase from Pseudomonas syringae), two fructooligosaccharide preparations with different composition, sucrose and fructose were tested as substrates. 25988123 4 77 dep polyfructans 585:596 arg1 polyfructans 585:596 The polyfructans inulin (from chicory) and levan (synthesized using levansucrase from Pseudomonas syringae), two fructooligosaccharide preparations with different composition 581:754 The polyfructans inulin (from chicory) and levan (synthesized using levansucrase from Pseudomonas syringae), two fructooligosaccharide preparations with different composition 581:754 The polyfructans inulin (from chicory) and levan (synthesized using levansucrase from Pseudomonas syringae), two fructooligosaccharide preparations with different composition, sucrose and fructose were tested as substrates. 25988123 4 77 dep polyfructans 585:596 arg1 preparations 716:727 two fructooligosaccharide preparations 690:727 two fructooligosaccharide preparations with different composition 690:754 The polyfructans inulin (from chicory) and levan (synthesized using levansucrase from Pseudomonas syringae), two fructooligosaccharide preparations with different composition, sucrose and fructose were tested as substrates. 25988123 1 78 theme Bacteroides 134:144 arg1 thetaiotaomicron 146:161 Bacteroides thetaiotaomicron 134:161 Bacteroides thetaiotaomicron 134:161 Bacteroides thetaiotaomicron is commonly found in the human colon and stabilizes its ecosystem by catabolism of various polysaccharides. 25988123 8 79 theme lactic 1302:1307 arg1 production 1314:1323 increased lactic acid production 1292:1323 increased lactic acid production 1292:1323 In amino acid-restricted medium, fermentation leading to acetic acid formation was dominant at the beginning of growth (up to 24 h), followed by increased lactic acid production, and mainly propionic and succinic acids were produced at the end of fermentation. 25988123 8 80 theme propionic 1337:1345 arg1 acids 1360:1364 mainly propionic and succinic acids 1330:1364 mainly propionic and succinic acids 1330:1364 In amino acid-restricted medium, fermentation leading to acetic acid formation was dominant at the beginning of growth (up to 24 h), followed by increased lactic acid production, and mainly propionic and succinic acids were produced at the end of fermentation. 25988123 7 81 contain containing 1071:1080 arg1 medium 1064:1069 the carbohydrate free medium 1042:1069 the carbohydrate free medium containing amino acids 1042:1092 Bacterial growth was not detected either in the carbohydrate free medium containing amino acids or in the medium with inulin as a sole carbohydrate. 25988123 7 81 contain containing 1071:1080 arg2 acids 1088:1092 amino acids 1082:1092 amino acids 1082:1092 Bacterial growth was not detected either in the carbohydrate free medium containing amino acids or in the medium with inulin as a sole carbohydrate. 25988123 11 82 from influence 1781:1789 arg1 metabolism 1817:1826 fructan metabolism 1809:1826 fructan metabolism in B. thetaiotaomicron 1809:1849 The study revealed the influence of amino acids on fructan metabolism in B. thetaiotaomicron and showed that defined growth media are invaluable in elucidating quantitative metabolic profiles of the bacteria. 25988123 8 83 theme succinic 1351:1358 arg1 acids 1360:1364 mainly propionic and succinic acids 1330:1364 mainly propionic and succinic acids 1330:1364 In amino acid-restricted medium, fermentation leading to acetic acid formation was dominant at the beginning of growth (up to 24 h), followed by increased lactic acid production, and mainly propionic and succinic acids were produced at the end of fermentation. 25988123 5 84 theme power-time 822:831 arg1 specific 855:862 specific 855:862 specific 855:862 The calorimetric power-time curves were substrate specific and typically multiauxic. 25988123 5 84 theme power-time 822:831 arg1 curves 833:838 The calorimetric power-time curves 805:838 The calorimetric power-time curves 805:838 The calorimetric power-time curves were substrate specific and typically multiauxic. 25988123 11 85 theme defined 1867:1873 arg1 media 1882:1886 defined growth media 1867:1886 defined growth media 1867:1886 The study revealed the influence of amino acids on fructan metabolism in B. thetaiotaomicron and showed that defined growth media are invaluable in elucidating quantitative metabolic profiles of the bacteria. 25988123 4 86 dep levan 624:628 arg1 synthesized 631:641 synthesized 631:641 synthesized using levansucrase from Pseudomonas syringae 631:686 The polyfructans inulin (from chicory) and levan (synthesized using levansucrase from Pseudomonas syringae), two fructooligosaccharide preparations with different composition, sucrose and fructose were tested as substrates. 25988123 3 87 theme 2079 419:422 arg1 growth 385:390 The growth 381:390 The growth 381:390 The growth of B. thetaiotaomicron DSM 2079 in two defined media containing mineral salts and vitamins, and supplemented with either 20 or 2 amino acids, was studied in an isothermal microcalorimeter. 25988123 3 88 theme mineral 456:462 arg1 salts 464:468 mineral salts 456:468 mineral salts 456:468 The growth of B. thetaiotaomicron DSM 2079 in two defined media containing mineral salts and vitamins, and supplemented with either 20 or 2 amino acids, was studied in an isothermal microcalorimeter. 25988123 0 89 theme Acid 52:55 arg1 Degradation 0:10 Degradation 0:10 Degradation of Fructans 0:22 Degradation of Fructans and Production of Propionic Acid by Bacteroides thetaiotaomicron are Enhanced by the Shortage of Amino Acids. 25988123 0 89 theme Acid 52:55 arg1 Production 28:37 Production 28:37 Production of Propionic Acid by Bacteroides thetaiotaomicron 28:87 Degradation of Fructans and Production of Propionic Acid by Bacteroides thetaiotaomicron are Enhanced by the Shortage of Amino Acids. 25988123 13 90 theme further 2131:2137 arg1 experiments 2139:2149 further experiments 2131:2149 further experiments 2131:2149 The effect of levan on balancing or modifying colon microbiota will be studied in further experiments. 25988123 0 91 theme Acids 127:131 arg1 Shortage 109:116 the Shortage 105:116 the Shortage of Amino Acids 105:131 Degradation of Fructans and Production of Propionic Acid by Bacteroides thetaiotaomicron are Enhanced by the Shortage of Amino Acids. 25988123 2 92 theme fructans 335:342 arg1 metabolism 305:314 the metabolism 301:314 the metabolism of amino acids and fructans in B. thetaiotaomicron 301:365 A model of cross-talk between the metabolism of amino acids and fructans in B. thetaiotaomicron was proposed. 25988123 9 93 theme acids 1588:1592 arg1 consumption 1547:1557 extensive consumption 1537:1557 extensive consumption (up to 17 mmol/gDW) of amino acids, especially Ser, Thr, and Asp 1537:1622 In the medium supplemented with 20 amino acids, the highest production of d-lactate (82 ± 33 mmol/gDW) occurred in parallel with extensive consumption (up to 17 mmol/gDW) of amino acids, especially Ser, Thr, and Asp. 25988123 8 94 theme fermentation 1394:1405 arg1 end 1387:1389 the end 1383:1389 the end of fermentation 1383:1405 In amino acid-restricted medium, fermentation leading to acetic acid formation was dominant at the beginning of growth (up to 24 h), followed by increased lactic acid production, and mainly propionic and succinic acids were produced at the end of fermentation. 25988123 2 95 theme acids 325:329 arg1 metabolism 305:314 the metabolism 301:314 the metabolism of amino acids and fructans in B. thetaiotaomicron 301:365 A model of cross-talk between the metabolism of amino acids and fructans in B. thetaiotaomicron was proposed. 25988123 8 96 from medium 1172:1177 arg1 dominant 1230:1237 dominant 1230:1237 dominant 1230:1237 In amino acid-restricted medium, fermentation leading to acetic acid formation was dominant at the beginning of growth (up to 24 h), followed by increased lactic acid production, and mainly propionic and succinic acids were produced at the end of fermentation. 25988123 4 97 with preparations 716:727 arg1 composition 744:754 different composition 734:754 different composition 734:754 The polyfructans inulin (from chicory) and levan (synthesized using levansucrase from Pseudomonas syringae), two fructooligosaccharide preparations with different composition, sucrose and fructose were tested as substrates. 25988123 11 98 theme fructan 1809:1815 arg1 metabolism 1817:1826 fructan metabolism 1809:1826 fructan metabolism in B. thetaiotaomicron 1809:1849 The study revealed the influence of amino acids on fructan metabolism in B. thetaiotaomicron and showed that defined growth media are invaluable in elucidating quantitative metabolic profiles of the bacteria. 26536879 4 0 theme nucleic 894:900 arg1 macromolecule 838:850 each constitutive macromolecule 820:850 each constitutive macromolecule (i.e., proteins, lipids, polysaccharides, nucleic acids) 820:907 The biomass composition and thus production were integrated considering the major biochemical synthesis reactions from monomers to each constitutive macromolecule (i.e., proteins, lipids, polysaccharides, nucleic acids). 26536879 4 0 theme nucleic 894:900 arg1 acids 902:906 nucleic acids 894:906 nucleic acids 894:906 The biomass composition and thus production were integrated considering the major biochemical synthesis reactions from monomers to each constitutive macromolecule (i.e., proteins, lipids, polysaccharides, nucleic acids). 26536879 8 1 theme oxygen 1344:1349 arg1 requirement 1351:1361 an oxygen requirement 1341:1361 an oxygen requirement of 0.33 moloxygen/molxylose linked to the cofactors of the xylose reductase 1341:1437 The maximal theoretical yield was calculated at 0.62 Cmolethanol/Cmolxylose for an oxygen requirement of 0.33 moloxygen/molxylose linked to the cofactors of the xylose reductase. 26536879 1 2 theme Candida 234:240 arg1 strain 251:256 Candida shehatae strain 234:256 Candida shehatae strain 234:256 A metabolic flux analysis (MFA) model was developed to optimize the xylose conversion into ethanol using Candida shehatae strain. 26536879 7 3 used utilized 1137:1144 arg2 model 1127:1131 The metabolic model 1113:1131 The metabolic model 1113:1131 The metabolic model was utilized to determine the theoretical yield taking into account oxido-reductive balance and to optimize ethanol production. 26536879 6 4 theme model 1060:1064 arg1 accuracy 1044:1051 the accuracy 1040:1051 the accuracy of the model 1040:1064 A first experiment allowed was to verify the accuracy of the model by comparing calculated and experimental data. 26536879 8 5 attach linked 1391:1396 arg2 requirement 1351:1361 an oxygen requirement 1341:1361 an oxygen requirement of 0.33 moloxygen/molxylose linked to the cofactors of the xylose reductase 1341:1437 The maximal theoretical yield was calculated at 0.62 Cmolethanol/Cmolxylose for an oxygen requirement of 0.33 moloxygen/molxylose linked to the cofactors of the xylose reductase. 26536879 8 5 attach linked 1391:1396 arg1 cofactors 1405:1413 the cofactors 1401:1413 the cofactors of the xylose reductase 1401:1437 The maximal theoretical yield was calculated at 0.62 Cmolethanol/Cmolxylose for an oxygen requirement of 0.33 moloxygen/molxylose linked to the cofactors of the xylose reductase. 26536879 1 6 theme shehatae 242:249 arg1 strain 251:256 Candida shehatae strain 234:256 Candida shehatae strain 234:256 A metabolic flux analysis (MFA) model was developed to optimize the xylose conversion into ethanol using Candida shehatae strain. 26536879 0 7 theme C5-fermenting 91:103 arg1 shehatae 119:126 the natural C5-fermenting yeast Candida shehatae 79:126 the natural C5-fermenting yeast Candida shehatae 79:126 Metabolic flux analysis model for optimizing xylose conversion into ethanol by the natural C5-fermenting yeast Candida shehatae. 26536879 9 8 theme oxygen/xylose 1559:1571 arg1 lower 1545:1549 lower 1545:1549 lower 1545:1549 Cultivations in chemostat mode allowed the fine tuning of both xylose and oxygen uptakes and showed that lower was the oxygen/xylose ratio, higher was the ethanol production yield. 26536879 9 8 theme oxygen/xylose 1559:1571 arg1 ratio 1573:1577 the oxygen/xylose ratio 1555:1577 the oxygen/xylose ratio 1555:1577 Cultivations in chemostat mode allowed the fine tuning of both xylose and oxygen uptakes and showed that lower was the oxygen/xylose ratio, higher was the ethanol production yield. 26536879 9 9 theme production 1603:1612 arg1 yield 1614:1618 the ethanol production yield 1591:1618 the ethanol production yield 1591:1618 Cultivations in chemostat mode allowed the fine tuning of both xylose and oxygen uptakes and showed that lower was the oxygen/xylose ratio, higher was the ethanol production yield. 26536879 9 9 theme production 1603:1612 arg1 higher 1580:1585 higher 1580:1585 higher 1580:1585 Cultivations in chemostat mode allowed the fine tuning of both xylose and oxygen uptakes and showed that lower was the oxygen/xylose ratio, higher was the ethanol production yield. 26536879 9 10 theme chemostat 1456:1464 arg1 mode 1466:1469 chemostat mode 1456:1469 chemostat mode 1456:1469 Cultivations in chemostat mode allowed the fine tuning of both xylose and oxygen uptakes and showed that lower was the oxygen/xylose ratio, higher was the ethanol production yield. 26536879 0 11 theme natural 83:89 arg1 shehatae 119:126 the natural C5-fermenting yeast Candida shehatae 79:126 the natural C5-fermenting yeast Candida shehatae 79:126 Metabolic flux analysis model for optimizing xylose conversion into ethanol by the natural C5-fermenting yeast Candida shehatae. 26536879 4 12 dep proteins 859:866 arg1 i.e. 853:856 i.e. 853:856 i.e. 853:856 The biomass composition and thus production were integrated considering the major biochemical synthesis reactions from monomers to each constitutive macromolecule (i.e., proteins, lipids, polysaccharides, nucleic acids). 26536879 10 13 theme 0.47 moloxygen/molxylose 1735:1758 arg1 supply 1725:1730 an oxygen supply 1715:1730 an oxygen supply of 0.47 moloxygen/molxylose 1715:1758 The best experimental ethanol production yield (0.51 Cmolethanol/Cmolxylose) was obtained for an oxygen supply of 0.47 moloxygen/molxylose. 26536879 3 14 theme phosphate 481:489 arg1 pathway 491:497 the pentose phosphate pathway 469:497 the pentose phosphate pathway 469:497 The model included the pentose phosphate pathway, glycolysis, synthesis of major metabolites like ethanol, acetic acid and glycerol, the tricarboxylic acid cycle as well as the respiratory chain, the cofactor balance, and the maintenance. 26536879 3 14 theme phosphate 481:489 arg1 cycle 606:610 the tricarboxylic acid cycle 583:610 the tricarboxylic acid cycle 583:610 The model included the pentose phosphate pathway, glycolysis, synthesis of major metabolites like ethanol, acetic acid and glycerol, the tricarboxylic acid cycle as well as the respiratory chain, the cofactor balance, and the maintenance. 26536879 3 14 theme phosphate 481:489 arg1 synthesis 512:520 synthesis 512:520 synthesis of major metabolites like ethanol, acetic acid and glycerol 512:580 The model included the pentose phosphate pathway, glycolysis, synthesis of major metabolites like ethanol, acetic acid and glycerol, the tricarboxylic acid cycle as well as the respiratory chain, the cofactor balance, and the maintenance. 26536879 3 14 theme phosphate 481:489 arg1 glycolysis 500:509 glycolysis 500:509 glycolysis 500:509 The model included the pentose phosphate pathway, glycolysis, synthesis of major metabolites like ethanol, acetic acid and glycerol, the tricarboxylic acid cycle as well as the respiratory chain, the cofactor balance, and the maintenance. 26536879 0 15 theme Candida 111:117 arg1 shehatae 119:126 the natural C5-fermenting yeast Candida shehatae 79:126 the natural C5-fermenting yeast Candida shehatae 79:126 Metabolic flux analysis model for optimizing xylose conversion into ethanol by the natural C5-fermenting yeast Candida shehatae. 26536879 2 16 theme metabolic 264:272 arg1 model 274:278 This metabolic model 259:278 This metabolic model 259:278 This metabolic model was compartmented and constructed with xylose as carbon substrate integrating the enzymatic duality of the first step of xylose degradation via an algebraic coefficient. 26536879 2 16 theme metabolic 264:272 arg1 substrate 336:344 carbon substrate 329:344 carbon substrate integrating the enzymatic duality of the first step of xylose degradation via an algebraic coefficient 329:447 This metabolic model was compartmented and constructed with xylose as carbon substrate integrating the enzymatic duality of the first step of xylose degradation via an algebraic coefficient. 26536879 2 17 theme step 393:396 arg1 duality 372:378 the enzymatic duality 358:378 the enzymatic duality of the first step of xylose degradation 358:418 This metabolic model was compartmented and constructed with xylose as carbon substrate integrating the enzymatic duality of the first step of xylose degradation via an algebraic coefficient. 26536879 0 18 theme yeast 105:109 arg1 shehatae 119:126 the natural C5-fermenting yeast Candida shehatae 79:126 the natural C5-fermenting yeast Candida shehatae 79:126 Metabolic flux analysis model for optimizing xylose conversion into ethanol by the natural C5-fermenting yeast Candida shehatae. 26536879 8 19 theme 0.33 moloxygen/molxylose 1366:1389 arg1 requirement 1351:1361 an oxygen requirement 1341:1361 an oxygen requirement of 0.33 moloxygen/molxylose linked to the cofactors of the xylose reductase 1341:1437 The maximal theoretical yield was calculated at 0.62 Cmolethanol/Cmolxylose for an oxygen requirement of 0.33 moloxygen/molxylose linked to the cofactors of the xylose reductase. 26536879 3 20 theme metabolites 531:541 arg1 pathway 491:497 the pentose phosphate pathway 469:497 the pentose phosphate pathway 469:497 The model included the pentose phosphate pathway, glycolysis, synthesis of major metabolites like ethanol, acetic acid and glycerol, the tricarboxylic acid cycle as well as the respiratory chain, the cofactor balance, and the maintenance. 26536879 3 20 theme metabolites 531:541 arg1 synthesis 512:520 synthesis 512:520 synthesis of major metabolites like ethanol, acetic acid and glycerol 512:580 The model included the pentose phosphate pathway, glycolysis, synthesis of major metabolites like ethanol, acetic acid and glycerol, the tricarboxylic acid cycle as well as the respiratory chain, the cofactor balance, and the maintenance. 26536879 2 21 theme first 387:391 arg1 step 393:396 the first step 383:396 the first step of xylose degradation 383:418 This metabolic model was compartmented and constructed with xylose as carbon substrate integrating the enzymatic duality of the first step of xylose degradation via an algebraic coefficient. 26536879 0 22 theme flux 10:13 arg1 analysis 15:22 Metabolic flux analysis 0:22 Metabolic flux analysis 0:22 Metabolic flux analysis model for optimizing xylose conversion into ethanol by the natural C5-fermenting yeast Candida shehatae. 26536879 7 23 theme oxido-reductive 1201:1215 arg1 balance 1217:1223 oxido-reductive balance 1201:1223 oxido-reductive balance 1201:1223 The metabolic model was utilized to determine the theoretical yield taking into account oxido-reductive balance and to optimize ethanol production. 26536879 9 24 theme fine 1483:1486 arg1 tuning 1488:1493 the fine tuning 1479:1493 the fine tuning of both xylose and oxygen uptakes 1479:1527 Cultivations in chemostat mode allowed the fine tuning of both xylose and oxygen uptakes and showed that lower was the oxygen/xylose ratio, higher was the ethanol production yield. 26536879 0 25 theme Metabolic 0:8 arg1 analysis 15:22 Metabolic flux analysis 0:22 Metabolic flux analysis 0:22 Metabolic flux analysis model for optimizing xylose conversion into ethanol by the natural C5-fermenting yeast Candida shehatae. 26536879 10 26 theme experimental 1630:1641 arg1 0.51 Cmolethanol/Cmolxylose 1669:1695 0.51 Cmolethanol/Cmolxylose 1669:1695 0.51 Cmolethanol/Cmolxylose 1669:1695 The best experimental ethanol production yield (0.51 Cmolethanol/Cmolxylose) was obtained for an oxygen supply of 0.47 moloxygen/molxylose. 26536879 10 26 theme experimental 1630:1641 arg1 yield 1662:1666 The best experimental ethanol production yield 1621:1666 The best experimental ethanol production yield (0.51 Cmolethanol/Cmolxylose) 1621:1696 The best experimental ethanol production yield (0.51 Cmolethanol/Cmolxylose) was obtained for an oxygen supply of 0.47 moloxygen/molxylose. 26536879 4 27 theme biomass 693:699 arg1 composition 701:711 The biomass composition 689:711 The biomass composition and thus production 689:731 The biomass composition and thus production were integrated considering the major biochemical synthesis reactions from monomers to each constitutive macromolecule (i.e., proteins, lipids, polysaccharides, nucleic acids). 26536879 5 28 theme equation 967:974 arg1 system 976:981 a 122-linear equation system 954:981 a 122-linear equation system to be resolved 954:996 The construction of the model resulted into a 122-linear equation system to be resolved. 26536879 2 29 theme algebraic 427:435 arg1 coefficient 437:447 an algebraic coefficient 424:447 an algebraic coefficient 424:447 This metabolic model was compartmented and constructed with xylose as carbon substrate integrating the enzymatic duality of the first step of xylose degradation via an algebraic coefficient. 26536879 8 30 theme reductase 1429:1437 arg1 cofactors 1405:1413 the cofactors 1401:1413 the cofactors of the xylose reductase 1401:1437 The maximal theoretical yield was calculated at 0.62 Cmolethanol/Cmolxylose for an oxygen requirement of 0.33 moloxygen/molxylose linked to the cofactors of the xylose reductase. 26536879 5 31 theme model 934:938 arg1 construction 914:925 The construction 910:925 The construction of the model 910:938 The construction of the model resulted into a 122-linear equation system to be resolved. 26536879 10 32 theme oxygen 1718:1723 arg1 supply 1725:1730 an oxygen supply 1715:1730 an oxygen supply of 0.47 moloxygen/molxylose 1715:1758 The best experimental ethanol production yield (0.51 Cmolethanol/Cmolxylose) was obtained for an oxygen supply of 0.47 moloxygen/molxylose. 26536879 9 33 theme xylose 1503:1508 arg1 tuning 1488:1493 the fine tuning 1479:1493 the fine tuning of both xylose and oxygen uptakes 1479:1527 Cultivations in chemostat mode allowed the fine tuning of both xylose and oxygen uptakes and showed that lower was the oxygen/xylose ratio, higher was the ethanol production yield. 26536879 3 34 theme major 525:529 arg1 glycerol 573:580 glycerol 573:580 glycerol 573:580 The model included the pentose phosphate pathway, glycolysis, synthesis of major metabolites like ethanol, acetic acid and glycerol, the tricarboxylic acid cycle as well as the respiratory chain, the cofactor balance, and the maintenance. 26536879 3 34 theme major 525:529 arg1 acid 564:567 acetic acid 557:567 acetic acid 557:567 The model included the pentose phosphate pathway, glycolysis, synthesis of major metabolites like ethanol, acetic acid and glycerol, the tricarboxylic acid cycle as well as the respiratory chain, the cofactor balance, and the maintenance. 26536879 3 34 theme major 525:529 arg1 metabolites 531:541 major metabolites 525:541 major metabolites like ethanol 525:554 The model included the pentose phosphate pathway, glycolysis, synthesis of major metabolites like ethanol, acetic acid and glycerol, the tricarboxylic acid cycle as well as the respiratory chain, the cofactor balance, and the maintenance. 26536879 3 35 theme respiratory 627:637 arg1 chain 639:643 the respiratory chain 623:643 the respiratory chain 623:643 The model included the pentose phosphate pathway, glycolysis, synthesis of major metabolites like ethanol, acetic acid and glycerol, the tricarboxylic acid cycle as well as the respiratory chain, the cofactor balance, and the maintenance. 26536879 3 36 theme acetic 557:562 arg1 acid 564:567 acetic acid 557:567 acetic acid 557:567 The model included the pentose phosphate pathway, glycolysis, synthesis of major metabolites like ethanol, acetic acid and glycerol, the tricarboxylic acid cycle as well as the respiratory chain, the cofactor balance, and the maintenance. 26536879 3 36 theme acetic 557:562 arg1 metabolites 531:541 major metabolites 525:541 major metabolites like ethanol 525:554 The model included the pentose phosphate pathway, glycolysis, synthesis of major metabolites like ethanol, acetic acid and glycerol, the tricarboxylic acid cycle as well as the respiratory chain, the cofactor balance, and the maintenance. 26536879 2 37 theme degradation 408:418 arg1 step 393:396 the first step 383:396 the first step of xylose degradation 383:418 This metabolic model was compartmented and constructed with xylose as carbon substrate integrating the enzymatic duality of the first step of xylose degradation via an algebraic coefficient. 26536879 9 38 theme uptakes 1521:1527 arg1 tuning 1488:1493 the fine tuning 1479:1493 the fine tuning of both xylose and oxygen uptakes 1479:1527 Cultivations in chemostat mode allowed the fine tuning of both xylose and oxygen uptakes and showed that lower was the oxygen/xylose ratio, higher was the ethanol production yield. 26536879 9 39 from Cultivations 1440:1451 arg1 mode 1466:1469 chemostat mode 1456:1469 chemostat mode 1456:1469 Cultivations in chemostat mode allowed the fine tuning of both xylose and oxygen uptakes and showed that lower was the oxygen/xylose ratio, higher was the ethanol production yield. 26536879 7 40 theme ethanol 1241:1247 arg1 production 1249:1258 ethanol production 1241:1258 ethanol production 1241:1258 The metabolic model was utilized to determine the theoretical yield taking into account oxido-reductive balance and to optimize ethanol production. 26536879 8 41 theme xylose 1422:1427 arg1 reductase 1429:1437 the xylose reductase 1418:1437 the xylose reductase 1418:1437 The maximal theoretical yield was calculated at 0.62 Cmolethanol/Cmolxylose for an oxygen requirement of 0.33 moloxygen/molxylose linked to the cofactors of the xylose reductase. 26536879 2 42 theme xylose 401:406 arg1 degradation 408:418 xylose degradation 401:418 xylose degradation 401:418 This metabolic model was compartmented and constructed with xylose as carbon substrate integrating the enzymatic duality of the first step of xylose degradation via an algebraic coefficient. 26536879 10 43 theme production 1651:1660 arg1 0.51 Cmolethanol/Cmolxylose 1669:1695 0.51 Cmolethanol/Cmolxylose 1669:1695 0.51 Cmolethanol/Cmolxylose 1669:1695 The best experimental ethanol production yield (0.51 Cmolethanol/Cmolxylose) was obtained for an oxygen supply of 0.47 moloxygen/molxylose. 26536879 10 43 theme production 1651:1660 arg1 yield 1662:1666 The best experimental ethanol production yield 1621:1666 The best experimental ethanol production yield (0.51 Cmolethanol/Cmolxylose) 1621:1696 The best experimental ethanol production yield (0.51 Cmolethanol/Cmolxylose) was obtained for an oxygen supply of 0.47 moloxygen/molxylose. 26536879 8 44 theme theoretical 1273:1283 arg1 yield 1285:1289 The maximal theoretical yield 1261:1289 The maximal theoretical yield 1261:1289 The maximal theoretical yield was calculated at 0.62 Cmolethanol/Cmolxylose for an oxygen requirement of 0.33 moloxygen/molxylose linked to the cofactors of the xylose reductase. 26536879 3 45 theme tricarboxylic 587:599 arg1 pathway 491:497 the pentose phosphate pathway 469:497 the pentose phosphate pathway 469:497 The model included the pentose phosphate pathway, glycolysis, synthesis of major metabolites like ethanol, acetic acid and glycerol, the tricarboxylic acid cycle as well as the respiratory chain, the cofactor balance, and the maintenance. 26536879 3 45 theme tricarboxylic 587:599 arg1 cycle 606:610 the tricarboxylic acid cycle 583:610 the tricarboxylic acid cycle 583:610 The model included the pentose phosphate pathway, glycolysis, synthesis of major metabolites like ethanol, acetic acid and glycerol, the tricarboxylic acid cycle as well as the respiratory chain, the cofactor balance, and the maintenance. 26536879 1 46 theme xylose 197:202 arg1 conversion 204:213 the xylose conversion 193:213 the xylose conversion into ethanol using Candida shehatae strain 193:256 A metabolic flux analysis (MFA) model was developed to optimize the xylose conversion into ethanol using Candida shehatae strain. 26536879 10 47 theme ethanol 1643:1649 arg1 0.51 Cmolethanol/Cmolxylose 1669:1695 0.51 Cmolethanol/Cmolxylose 1669:1695 0.51 Cmolethanol/Cmolxylose 1669:1695 The best experimental ethanol production yield (0.51 Cmolethanol/Cmolxylose) was obtained for an oxygen supply of 0.47 moloxygen/molxylose. 26536879 10 47 theme ethanol 1643:1649 arg1 yield 1662:1666 The best experimental ethanol production yield 1621:1666 The best experimental ethanol production yield (0.51 Cmolethanol/Cmolxylose) 1621:1696 The best experimental ethanol production yield (0.51 Cmolethanol/Cmolxylose) was obtained for an oxygen supply of 0.47 moloxygen/molxylose. 26536879 4 48 theme constitutive 825:836 arg1 macromolecule 838:850 each constitutive macromolecule 820:850 each constitutive macromolecule (i.e., proteins, lipids, polysaccharides, nucleic acids) 820:907 The biomass composition and thus production were integrated considering the major biochemical synthesis reactions from monomers to each constitutive macromolecule (i.e., proteins, lipids, polysaccharides, nucleic acids). 26536879 4 48 theme constitutive 825:836 arg1 acids 902:906 nucleic acids 894:906 nucleic acids 894:906 The biomass composition and thus production were integrated considering the major biochemical synthesis reactions from monomers to each constitutive macromolecule (i.e., proteins, lipids, polysaccharides, nucleic acids). 26536879 9 49 theme oxygen 1514:1519 arg1 uptakes 1521:1527 oxygen uptakes 1514:1527 oxygen uptakes 1514:1527 Cultivations in chemostat mode allowed the fine tuning of both xylose and oxygen uptakes and showed that lower was the oxygen/xylose ratio, higher was the ethanol production yield. 26536879 0 50 theme xylose 45:50 arg1 conversion 52:61 xylose conversion 45:61 xylose conversion into ethanol by the natural C5-fermenting yeast Candida shehatae 45:126 Metabolic flux analysis model for optimizing xylose conversion into ethanol by the natural C5-fermenting yeast Candida shehatae. 26536879 3 51 theme cofactor 650:657 arg1 balance 659:665 the cofactor balance 646:665 the cofactor balance 646:665 The model included the pentose phosphate pathway, glycolysis, synthesis of major metabolites like ethanol, acetic acid and glycerol, the tricarboxylic acid cycle as well as the respiratory chain, the cofactor balance, and the maintenance. 26536879 1 52 theme analysis 146:153 arg1 model 161:165 A metabolic flux analysis (MFA) model 129:165 A metabolic flux analysis (MFA) model 129:165 A metabolic flux analysis (MFA) model was developed to optimize the xylose conversion into ethanol using Candida shehatae strain. 26536879 2 53 theme carbon 329:334 arg1 model 274:278 This metabolic model 259:278 This metabolic model 259:278 This metabolic model was compartmented and constructed with xylose as carbon substrate integrating the enzymatic duality of the first step of xylose degradation via an algebraic coefficient. 26536879 2 53 theme carbon 329:334 arg1 substrate 336:344 carbon substrate 329:344 carbon substrate integrating the enzymatic duality of the first step of xylose degradation via an algebraic coefficient 329:447 This metabolic model was compartmented and constructed with xylose as carbon substrate integrating the enzymatic duality of the first step of xylose degradation via an algebraic coefficient. 26536879 6 54 theme first 1001:1005 arg1 experiment 1007:1016 A first experiment 999:1016 A first experiment allowed 999:1024 A first experiment allowed was to verify the accuracy of the model by comparing calculated and experimental data. 26536879 7 55 theme metabolic 1117:1125 arg1 model 1127:1131 The metabolic model 1113:1131 The metabolic model 1113:1131 The metabolic model was utilized to determine the theoretical yield taking into account oxido-reductive balance and to optimize ethanol production. 26536879 4 56 theme synthesis 783:791 arg1 reactions 793:801 the major biochemical synthesis reactions 761:801 the major biochemical synthesis reactions from monomers to each constitutive macromolecule (i.e., proteins, lipids, polysaccharides, nucleic acids) 761:907 The biomass composition and thus production were integrated considering the major biochemical synthesis reactions from monomers to each constitutive macromolecule (i.e., proteins, lipids, polysaccharides, nucleic acids). 26536879 4 57 from monomers 808:815 arg1 reactions 793:801 the major biochemical synthesis reactions 761:801 the major biochemical synthesis reactions from monomers to each constitutive macromolecule (i.e., proteins, lipids, polysaccharides, nucleic acids) 761:907 The biomass composition and thus production were integrated considering the major biochemical synthesis reactions from monomers to each constitutive macromolecule (i.e., proteins, lipids, polysaccharides, nucleic acids). 26536879 3 58 theme pentose 473:479 arg1 pathway 491:497 the pentose phosphate pathway 469:497 the pentose phosphate pathway 469:497 The model included the pentose phosphate pathway, glycolysis, synthesis of major metabolites like ethanol, acetic acid and glycerol, the tricarboxylic acid cycle as well as the respiratory chain, the cofactor balance, and the maintenance. 26536879 3 58 theme pentose 473:479 arg1 cycle 606:610 the tricarboxylic acid cycle 583:610 the tricarboxylic acid cycle 583:610 The model included the pentose phosphate pathway, glycolysis, synthesis of major metabolites like ethanol, acetic acid and glycerol, the tricarboxylic acid cycle as well as the respiratory chain, the cofactor balance, and the maintenance. 26536879 3 58 theme pentose 473:479 arg1 synthesis 512:520 synthesis 512:520 synthesis of major metabolites like ethanol, acetic acid and glycerol 512:580 The model included the pentose phosphate pathway, glycolysis, synthesis of major metabolites like ethanol, acetic acid and glycerol, the tricarboxylic acid cycle as well as the respiratory chain, the cofactor balance, and the maintenance. 26536879 3 58 theme pentose 473:479 arg1 glycolysis 500:509 glycolysis 500:509 glycolysis 500:509 The model included the pentose phosphate pathway, glycolysis, synthesis of major metabolites like ethanol, acetic acid and glycerol, the tricarboxylic acid cycle as well as the respiratory chain, the cofactor balance, and the maintenance. 26536879 9 59 theme ethanol 1595:1601 arg1 yield 1614:1618 the ethanol production yield 1591:1618 the ethanol production yield 1591:1618 Cultivations in chemostat mode allowed the fine tuning of both xylose and oxygen uptakes and showed that lower was the oxygen/xylose ratio, higher was the ethanol production yield. 26536879 9 59 theme ethanol 1595:1601 arg1 higher 1580:1585 higher 1580:1585 higher 1580:1585 Cultivations in chemostat mode allowed the fine tuning of both xylose and oxygen uptakes and showed that lower was the oxygen/xylose ratio, higher was the ethanol production yield. 26536879 8 60 theme maximal 1265:1271 arg1 yield 1285:1289 The maximal theoretical yield 1261:1289 The maximal theoretical yield 1261:1289 The maximal theoretical yield was calculated at 0.62 Cmolethanol/Cmolxylose for an oxygen requirement of 0.33 moloxygen/molxylose linked to the cofactors of the xylose reductase. 26536879 4 61 theme major 765:769 arg1 reactions 793:801 the major biochemical synthesis reactions 761:801 the major biochemical synthesis reactions from monomers to each constitutive macromolecule (i.e., proteins, lipids, polysaccharides, nucleic acids) 761:907 The biomass composition and thus production were integrated considering the major biochemical synthesis reactions from monomers to each constitutive macromolecule (i.e., proteins, lipids, polysaccharides, nucleic acids). 26536879 4 62 theme biochemical 771:781 arg1 reactions 793:801 the major biochemical synthesis reactions 761:801 the major biochemical synthesis reactions from monomers to each constitutive macromolecule (i.e., proteins, lipids, polysaccharides, nucleic acids) 761:907 The biomass composition and thus production were integrated considering the major biochemical synthesis reactions from monomers to each constitutive macromolecule (i.e., proteins, lipids, polysaccharides, nucleic acids). 26536879 1 63 theme metabolic 131:139 arg1 analysis 146:153 metabolic flux analysis 131:153 A metabolic flux analysis (MFA) model 129:165 A metabolic flux analysis (MFA) model was developed to optimize the xylose conversion into ethanol using Candida shehatae strain. 26536879 1 63 theme metabolic 131:139 arg1 MFA 156:158 MFA 156:158 MFA 156:158 A metabolic flux analysis (MFA) model was developed to optimize the xylose conversion into ethanol using Candida shehatae strain. 26536879 6 64 theme experimental 1094:1105 arg1 data 1107:1110 experimental data 1094:1110 experimental data 1094:1110 A first experiment allowed was to verify the accuracy of the model by comparing calculated and experimental data. 26536879 5 65 theme 122-linear 956:965 arg1 system 976:981 a 122-linear equation system 954:981 a 122-linear equation system to be resolved 954:996 The construction of the model resulted into a 122-linear equation system to be resolved. 26536879 3 66 theme acid 601:604 arg1 pathway 491:497 the pentose phosphate pathway 469:497 the pentose phosphate pathway 469:497 The model included the pentose phosphate pathway, glycolysis, synthesis of major metabolites like ethanol, acetic acid and glycerol, the tricarboxylic acid cycle as well as the respiratory chain, the cofactor balance, and the maintenance. 26536879 3 66 theme acid 601:604 arg1 cycle 606:610 the tricarboxylic acid cycle 583:610 the tricarboxylic acid cycle 583:610 The model included the pentose phosphate pathway, glycolysis, synthesis of major metabolites like ethanol, acetic acid and glycerol, the tricarboxylic acid cycle as well as the respiratory chain, the cofactor balance, and the maintenance. 26536879 1 67 theme flux 141:144 arg1 analysis 146:153 metabolic flux analysis 131:153 A metabolic flux analysis (MFA) model 129:165 A metabolic flux analysis (MFA) model was developed to optimize the xylose conversion into ethanol using Candida shehatae strain. 26536879 1 67 theme flux 141:144 arg1 MFA 156:158 MFA 156:158 MFA 156:158 A metabolic flux analysis (MFA) model was developed to optimize the xylose conversion into ethanol using Candida shehatae strain. 26536879 7 68 theme theoretical 1163:1173 arg1 yield 1175:1179 the theoretical yield 1159:1179 the theoretical yield taking into account oxido-reductive balance 1159:1223 The metabolic model was utilized to determine the theoretical yield taking into account oxido-reductive balance and to optimize ethanol production. 26536879 10 69 theme best 1625:1628 arg1 0.51 Cmolethanol/Cmolxylose 1669:1695 0.51 Cmolethanol/Cmolxylose 1669:1695 0.51 Cmolethanol/Cmolxylose 1669:1695 The best experimental ethanol production yield (0.51 Cmolethanol/Cmolxylose) was obtained for an oxygen supply of 0.47 moloxygen/molxylose. 26536879 10 69 theme best 1625:1628 arg1 yield 1662:1666 The best experimental ethanol production yield 1621:1666 The best experimental ethanol production yield (0.51 Cmolethanol/Cmolxylose) 1621:1696 The best experimental ethanol production yield (0.51 Cmolethanol/Cmolxylose) was obtained for an oxygen supply of 0.47 moloxygen/molxylose. 26536879 2 70 theme enzymatic 362:370 arg1 duality 372:378 the enzymatic duality 358:378 the enzymatic duality of the first step of xylose degradation 358:418 This metabolic model was compartmented and constructed with xylose as carbon substrate integrating the enzymatic duality of the first step of xylose degradation via an algebraic coefficient. 25844502 6 0 theme multivariate 770:781 arg1 analysis 783:790 multivariate analysis 770:790 multivariate analysis 770:790 In this study, the chemical composition of the two different ARs, which were collected in the Shanxi (wild) and Gansu (cultivated) provinces, were compared by NMR-based metabolic fingerprint coupled with multivariate analysis. 25844502 5 1 theme clinical 536:543 arg1 efficacy 545:552 the clinical efficacy 532:552 the clinical efficacy 532:552 A systematic comparison of cultivated AR (GS-AR) and wild AR (SX-AR) should be performed to ensure the clinical efficacy and safety. 25844502 5 2 theme cultivated 460:469 arg1 GS-AR 475:479 GS-AR 475:479 GS-AR 475:479 A systematic comparison of cultivated AR (GS-AR) and wild AR (SX-AR) should be performed to ensure the clinical efficacy and safety. 25844502 5 2 theme cultivated 460:469 arg1 AR 471:472 cultivated AR 460:472 cultivated AR (GS-AR) 460:480 A systematic comparison of cultivated AR (GS-AR) and wild AR (SX-AR) should be performed to ensure the clinical efficacy and safety. 25844502 1 3 theme herbal 124:129 arg1 Radix 94:98 Astragali Radix 84:98 Astragali Radix (AR) 84:103 Astragali Radix (AR) is a commonly used herbal drug in traditional chinese medicine and is widely used for the treatment of diabetes, cardiovascular diseases, nephropathy, and neuropathy. 25844502 1 3 theme herbal 124:129 arg1 drug 131:134 a commonly used herbal drug 108:134 a commonly used herbal drug in traditional chinese medicine 108:166 Astragali Radix (AR) is a commonly used herbal drug in traditional chinese medicine and is widely used for the treatment of diabetes, cardiovascular diseases, nephropathy, and neuropathy. 25844502 1 4 theme diabetes 208:215 arg1 treatment 195:203 the treatment 191:203 the treatment of diabetes, cardiovascular diseases, nephropathy, and neuropathy 191:269 Astragali Radix (AR) is a commonly used herbal drug in traditional chinese medicine and is widely used for the treatment of diabetes, cardiovascular diseases, nephropathy, and neuropathy. 25844502 0 5 theme Metabolomic 62:72 arg1 Approach 74:81 a ¹H NMR-Based Metabolomic Approach 47:81 a ¹H NMR-Based Metabolomic Approach 47:81 Comparison of Two Different Astragali Radix by a ¹H NMR-Based Metabolomic Approach. 25844502 10 6 theme diversity 1241:1249 arg1 evaluation 1207:1216 the evaluation 1203:1216 the evaluation of the consistency and diversity of herbal drugs 1203:1265 This study provided a novel and valuable method for the evaluation of the consistency and diversity of herbal drugs, and further studies should be conducted on the difference in polysaccharides as well as the biological effects between the two kinds of AR. 25844502 9 7 from alterations 1045:1055 arg1 lung 1104:1107 lung 1104:1107 lung 1104:1107 However, alterations among the endogenous metabolites in the serum, lung, liver, and spleen were relatively small. 25844502 9 7 from alterations 1045:1055 arg1 serum 1097:1101 serum 1097:1101 serum 1097:1101 However, alterations among the endogenous metabolites in the serum, lung, liver, and spleen were relatively small. 25844502 9 7 from alterations 1045:1055 arg1 liver 1110:1114 liver 1110:1114 liver 1110:1114 However, alterations among the endogenous metabolites in the serum, lung, liver, and spleen were relatively small. 25844502 9 7 from alterations 1045:1055 arg1 spleen 1121:1126 spleen 1121:1126 spleen 1121:1126 However, alterations among the endogenous metabolites in the serum, lung, liver, and spleen were relatively small. 25844502 10 8 theme drugs 1261:1265 arg1 diversity 1241:1249 diversity 1241:1249 diversity 1241:1249 This study provided a novel and valuable method for the evaluation of the consistency and diversity of herbal drugs, and further studies should be conducted on the difference in polysaccharides as well as the biological effects between the two kinds of AR. 25844502 10 8 theme drugs 1261:1265 arg1 consistency 1225:1235 consistency 1225:1235 consistency 1225:1235 This study provided a novel and valuable method for the evaluation of the consistency and diversity of herbal drugs, and further studies should be conducted on the difference in polysaccharides as well as the biological effects between the two kinds of AR. 25844502 10 9 theme further 1272:1278 arg1 studies 1280:1286 further studies 1272:1286 further studies 1272:1286 This study provided a novel and valuable method for the evaluation of the consistency and diversity of herbal drugs, and further studies should be conducted on the difference in polysaccharides as well as the biological effects between the two kinds of AR. 25844502 1 10 from drug 131:134 arg1 medicine 159:166 traditional chinese medicine 139:166 traditional chinese medicine 139:166 Astragali Radix (AR) is a commonly used herbal drug in traditional chinese medicine and is widely used for the treatment of diabetes, cardiovascular diseases, nephropathy, and neuropathy. 25844502 7 11 theme endogenous 847:856 arg1 metabolites 858:868 the endogenous metabolites 843:868 the endogenous metabolites 843:868 The SX-AR- and GS-AR-induced metabolic changes in the endogenous metabolites in mice were also compared. 25844502 1 12 theme cardiovascular 218:231 arg1 diseases 233:240 cardiovascular diseases 218:240 cardiovascular diseases 218:240 Astragali Radix (AR) is a commonly used herbal drug in traditional chinese medicine and is widely used for the treatment of diabetes, cardiovascular diseases, nephropathy, and neuropathy. 25844502 6 13 theme different 617:625 arg1 ARs 627:629 the two different ARs 609:629 the two different ARs 609:629 In this study, the chemical composition of the two different ARs, which were collected in the Shanxi (wild) and Gansu (cultivated) provinces, were compared by NMR-based metabolic fingerprint coupled with multivariate analysis. 25844502 4 14 theme wild 403:406 arg1 ARs 408:410 both cultivated and wild ARs 383:410 both cultivated and wild ARs 383:410 Hsiao, and both cultivated and wild ARs are used clinically. 25844502 7 15 theme GS-AR-induced 808:820 arg1 changes 832:838 The SX-AR- and GS-AR-induced metabolic changes 793:838 The SX-AR- and GS-AR-induced metabolic changes in the endogenous metabolites in mice 793:876 The SX-AR- and GS-AR-induced metabolic changes in the endogenous metabolites in mice were also compared. 25844502 7 16 from changes 832:838 arg1 metabolites 858:868 the endogenous metabolites 843:868 the endogenous metabolites 843:868 The SX-AR- and GS-AR-induced metabolic changes in the endogenous metabolites in mice were also compared. 25844502 7 16 from changes 832:838 arg1 mice 873:876 mice 873:876 mice 873:876 The SX-AR- and GS-AR-induced metabolic changes in the endogenous metabolites in mice were also compared. 25844502 1 17 theme diseases 233:240 arg1 treatment 195:203 the treatment 191:203 the treatment of diabetes, cardiovascular diseases, nephropathy, and neuropathy 191:269 Astragali Radix (AR) is a commonly used herbal drug in traditional chinese medicine and is widely used for the treatment of diabetes, cardiovascular diseases, nephropathy, and neuropathy. 25844502 6 18 theme metabolic 735:743 arg1 fingerprint 745:755 NMR-based metabolic fingerprint 725:755 NMR-based metabolic fingerprint coupled with multivariate analysis 725:790 In this study, the chemical composition of the two different ARs, which were collected in the Shanxi (wild) and Gansu (cultivated) provinces, were compared by NMR-based metabolic fingerprint coupled with multivariate analysis. 25844502 7 19 theme metabolic 822:830 arg1 changes 832:838 The SX-AR- and GS-AR-induced metabolic changes 793:838 The SX-AR- and GS-AR-induced metabolic changes in the endogenous metabolites in mice 793:876 The SX-AR- and GS-AR-induced metabolic changes in the endogenous metabolites in mice were also compared. 25844502 6 20 theme chemical 585:592 arg1 composition 594:604 the chemical composition 581:604 the chemical composition 581:604 In this study, the chemical composition of the two different ARs, which were collected in the Shanxi (wild) and Gansu (cultivated) provinces, were compared by NMR-based metabolic fingerprint coupled with multivariate analysis. 25844502 2 21 theme membranaceus 335:346 arg1 var 348:350 Astragalus membranaceus var 324:350 Astragalus membranaceus var 324:350 The main source of AR in China is the dried root of Astragalus membranaceus var. 25844502 6 22 theme NMR-based 725:733 arg1 fingerprint 745:755 NMR-based metabolic fingerprint 725:755 NMR-based metabolic fingerprint coupled with multivariate analysis 725:790 In this study, the chemical composition of the two different ARs, which were collected in the Shanxi (wild) and Gansu (cultivated) provinces, were compared by NMR-based metabolic fingerprint coupled with multivariate analysis. 25844502 7 23 theme SX-AR- 797:802 arg1 changes 832:838 The SX-AR- and GS-AR-induced metabolic changes 793:838 The SX-AR- and GS-AR-induced metabolic changes in the endogenous metabolites in mice 793:876 The SX-AR- and GS-AR-induced metabolic changes in the endogenous metabolites in mice were also compared. 25844502 6 24 dep Shanxi 660:665 arg1 wild 668:671 wild 668:671 wild 668:671 In this study, the chemical composition of the two different ARs, which were collected in the Shanxi (wild) and Gansu (cultivated) provinces, were compared by NMR-based metabolic fingerprint coupled with multivariate analysis. 25844502 2 25 theme Astragalus 324:333 arg1 var 348:350 Astragalus membranaceus var 324:350 Astragalus membranaceus var 324:350 The main source of AR in China is the dried root of Astragalus membranaceus var. 25844502 10 26 theme AR 1404:1405 arg1 kinds 1395:1399 the two kinds 1387:1399 the two kinds of AR 1387:1405 This study provided a novel and valuable method for the evaluation of the consistency and diversity of herbal drugs, and further studies should be conducted on the difference in polysaccharides as well as the biological effects between the two kinds of AR. 25844502 5 27 theme wild 486:489 arg1 AR 491:492 wild AR 486:492 wild AR (SX-AR) 486:500 A systematic comparison of cultivated AR (GS-AR) and wild AR (SX-AR) should be performed to ensure the clinical efficacy and safety. 25844502 5 27 theme wild 486:489 arg1 SX-AR 495:499 SX-AR 495:499 SX-AR 495:499 A systematic comparison of cultivated AR (GS-AR) and wild AR (SX-AR) should be performed to ensure the clinical efficacy and safety. 25844502 2 28 theme main 276:279 arg1 source 281:286 The main source 272:286 The main source of AR in China 272:301 The main source of AR in China is the dried root of Astragalus membranaceus var. 25844502 2 28 theme main 276:279 arg1 root 316:319 the dried root 306:319 the dried root of Astragalus membranaceus var 306:350 The main source of AR in China is the dried root of Astragalus membranaceus var. 25844502 1 29 theme chinese 151:157 arg1 medicine 159:166 traditional chinese medicine 139:166 traditional chinese medicine 139:166 Astragali Radix (AR) is a commonly used herbal drug in traditional chinese medicine and is widely used for the treatment of diabetes, cardiovascular diseases, nephropathy, and neuropathy. 25844502 5 30 theme AR 491:492 arg1 comparison 446:455 A systematic comparison 433:455 A systematic comparison of cultivated AR (GS-AR) and wild AR (SX-AR) 433:500 A systematic comparison of cultivated AR (GS-AR) and wild AR (SX-AR) should be performed to ensure the clinical efficacy and safety. 25844502 1 31 theme Astragali 84:92 arg1 AR 101:102 AR 101:102 AR 101:102 Astragali Radix (AR) is a commonly used herbal drug in traditional chinese medicine and is widely used for the treatment of diabetes, cardiovascular diseases, nephropathy, and neuropathy. 25844502 1 31 theme Astragali 84:92 arg1 Radix 94:98 Astragali Radix 84:98 Astragali Radix (AR) 84:103 Astragali Radix (AR) is a commonly used herbal drug in traditional chinese medicine and is widely used for the treatment of diabetes, cardiovascular diseases, nephropathy, and neuropathy. 25844502 1 31 theme Astragali 84:92 arg1 drug 131:134 a commonly used herbal drug 108:134 a commonly used herbal drug in traditional chinese medicine 108:166 Astragali Radix (AR) is a commonly used herbal drug in traditional chinese medicine and is widely used for the treatment of diabetes, cardiovascular diseases, nephropathy, and neuropathy. 25844502 0 32 theme Different 18:26 arg1 Radix 38:42 Two Different Astragali Radix 14:42 Two Different Astragali Radix 14:42 Comparison of Two Different Astragali Radix by a ¹H NMR-Based Metabolomic Approach. 25844502 1 33 theme nephropathy 243:253 arg1 treatment 195:203 the treatment 191:203 the treatment of diabetes, cardiovascular diseases, nephropathy, and neuropathy 191:269 Astragali Radix (AR) is a commonly used herbal drug in traditional chinese medicine and is widely used for the treatment of diabetes, cardiovascular diseases, nephropathy, and neuropathy. 25844502 10 34 theme novel 1173:1177 arg1 method 1192:1197 a novel and valuable method 1171:1197 a novel and valuable method for the evaluation of the consistency and diversity of herbal drugs 1171:1265 This study provided a novel and valuable method for the evaluation of the consistency and diversity of herbal drugs, and further studies should be conducted on the difference in polysaccharides as well as the biological effects between the two kinds of AR. 25844502 0 35 theme Radix 38:42 arg1 Comparison 0:9 Comparison 0:9 Comparison of Two Different Astragali Radix by a ¹H NMR-Based Metabolomic Approach. 0:82 Comparison of Two Different Astragali Radix by a ¹H NMR-Based Metabolomic Approach. 25844502 1 36 used used 182:185 arg2 drug 131:134 a commonly used herbal drug 108:134 a commonly used herbal drug in traditional chinese medicine 108:166 Astragali Radix (AR) is a commonly used herbal drug in traditional chinese medicine and is widely used for the treatment of diabetes, cardiovascular diseases, nephropathy, and neuropathy. 25844502 1 36 used used 182:185 arg2 AR 101:102 AR 101:102 AR 101:102 Astragali Radix (AR) is a commonly used herbal drug in traditional chinese medicine and is widely used for the treatment of diabetes, cardiovascular diseases, nephropathy, and neuropathy. 25844502 1 36 used used 182:185 arg2 Radix 94:98 Astragali Radix 84:98 Astragali Radix (AR) 84:103 Astragali Radix (AR) is a commonly used herbal drug in traditional chinese medicine and is widely used for the treatment of diabetes, cardiovascular diseases, nephropathy, and neuropathy. 25844502 0 37 theme Astragali 28:36 arg1 Radix 38:42 Two Different Astragali Radix 14:42 Two Different Astragali Radix 14:42 Comparison of Two Different Astragali Radix by a ¹H NMR-Based Metabolomic Approach. 25844502 1 38 theme neuropathy 260:269 arg1 treatment 195:203 the treatment 191:203 the treatment of diabetes, cardiovascular diseases, nephropathy, and neuropathy 191:269 Astragali Radix (AR) is a commonly used herbal drug in traditional chinese medicine and is widely used for the treatment of diabetes, cardiovascular diseases, nephropathy, and neuropathy. 25844502 4 39 theme cultivated 388:397 arg1 ARs 408:410 both cultivated and wild ARs 383:410 both cultivated and wild ARs 383:410 Hsiao, and both cultivated and wild ARs are used clinically. 25844502 4 40 used used 416:419 arg2 Hsiao 372:376 Hsiao 372:376 Hsiao 372:376 Hsiao, and both cultivated and wild ARs are used clinically. 25844502 4 40 used used 416:419 arg2 ARs 408:410 both cultivated and wild ARs 383:410 both cultivated and wild ARs 383:410 Hsiao, and both cultivated and wild ARs are used clinically. 25844502 5 41 theme AR 471:472 arg1 comparison 446:455 A systematic comparison 433:455 A systematic comparison of cultivated AR (GS-AR) and wild AR (SX-AR) 433:500 A systematic comparison of cultivated AR (GS-AR) and wild AR (SX-AR) should be performed to ensure the clinical efficacy and safety. 25844502 2 42 theme var 348:350 arg1 root 316:319 the dried root 306:319 the dried root of Astragalus membranaceus var 306:350 The main source of AR in China is the dried root of Astragalus membranaceus var. 25844502 2 42 theme var 348:350 arg1 source 281:286 The main source 272:286 The main source of AR in China 272:301 The main source of AR in China is the dried root of Astragalus membranaceus var. 25844502 6 43 dep provinces 697:705 arg1 cultivated 685:694 cultivated 685:694 cultivated 685:694 In this study, the chemical composition of the two different ARs, which were collected in the Shanxi (wild) and Gansu (cultivated) provinces, were compared by NMR-based metabolic fingerprint coupled with multivariate analysis. 25844502 10 44 theme biological 1360:1369 arg1 effects 1371:1377 the biological effects 1356:1377 polysaccharides as well as the biological effects 1329:1377 This study provided a novel and valuable method for the evaluation of the consistency and diversity of herbal drugs, and further studies should be conducted on the difference in polysaccharides as well as the biological effects between the two kinds of AR. 25844502 10 45 theme valuable 1183:1190 arg1 method 1192:1197 a novel and valuable method 1171:1197 a novel and valuable method for the evaluation of the consistency and diversity of herbal drugs 1171:1265 This study provided a novel and valuable method for the evaluation of the consistency and diversity of herbal drugs, and further studies should be conducted on the difference in polysaccharides as well as the biological effects between the two kinds of AR. 25844502 10 46 theme herbal 1254:1259 arg1 drugs 1261:1265 herbal drugs 1254:1265 herbal drugs 1254:1265 This study provided a novel and valuable method for the evaluation of the consistency and diversity of herbal drugs, and further studies should be conducted on the difference in polysaccharides as well as the biological effects between the two kinds of AR. 25844502 2 47 theme AR 291:292 arg1 source 281:286 The main source 272:286 The main source of AR in China 272:301 The main source of AR in China is the dried root of Astragalus membranaceus var. 25844502 2 47 theme AR 291:292 arg1 root 316:319 the dried root 306:319 the dried root of Astragalus membranaceus var 306:350 The main source of AR in China is the dried root of Astragalus membranaceus var. 25844502 9 48 theme endogenous 1067:1076 arg1 metabolites 1078:1088 the endogenous metabolites 1063:1088 the endogenous metabolites 1063:1088 However, alterations among the endogenous metabolites in the serum, lung, liver, and spleen were relatively small. 25844502 2 49 from source 281:286 arg1 China 297:301 China 297:301 China 297:301 The main source of AR in China is the dried root of Astragalus membranaceus var. 25844502 10 50 theme consistency 1225:1235 arg1 evaluation 1207:1216 the evaluation 1203:1216 the evaluation of the consistency and diversity of herbal drugs 1203:1265 This study provided a novel and valuable method for the evaluation of the consistency and diversity of herbal drugs, and further studies should be conducted on the difference in polysaccharides as well as the biological effects between the two kinds of AR. 25844502 6 51 theme ARs 627:629 arg1 composition 594:604 the chemical composition 581:604 the chemical composition 581:604 In this study, the chemical composition of the two different ARs, which were collected in the Shanxi (wild) and Gansu (cultivated) provinces, were compared by NMR-based metabolic fingerprint coupled with multivariate analysis. 25844502 5 52 theme systematic 435:444 arg1 comparison 446:455 A systematic comparison 433:455 A systematic comparison of cultivated AR (GS-AR) and wild AR (SX-AR) 433:500 A systematic comparison of cultivated AR (GS-AR) and wild AR (SX-AR) should be performed to ensure the clinical efficacy and safety. 25844502 10 53 from difference 1315:1324 arg1 polysaccharides 1329:1343 polysaccharides 1329:1343 polysaccharides as well as the biological effects 1329:1377 This study provided a novel and valuable method for the evaluation of the consistency and diversity of herbal drugs, and further studies should be conducted on the difference in polysaccharides as well as the biological effects between the two kinds of AR. 25844502 10 53 from difference 1315:1324 arg1 effects 1371:1377 the biological effects 1356:1377 polysaccharides as well as the biological effects 1329:1377 This study provided a novel and valuable method for the evaluation of the consistency and diversity of herbal drugs, and further studies should be conducted on the difference in polysaccharides as well as the biological effects between the two kinds of AR. 25844502 0 54 theme NMR-Based 52:60 arg1 Approach 74:81 a ¹H NMR-Based Metabolomic Approach 47:81 a ¹H NMR-Based Metabolomic Approach 47:81 Comparison of Two Different Astragali Radix by a ¹H NMR-Based Metabolomic Approach. 25844502 6 55 theme Gansu 678:682 arg1 provinces 697:705 the Shanxi (wild) and Gansu (cultivated) provinces 656:705 provinces 697:705 In this study, the chemical composition of the two different ARs, which were collected in the Shanxi (wild) and Gansu (cultivated) provinces, were compared by NMR-based metabolic fingerprint coupled with multivariate analysis. 25844502 10 56 dep consistency 1225:1235 arg1 the 1221:1223 the 1221:1223 the 1221:1223 This study provided a novel and valuable method for the evaluation of the consistency and diversity of herbal drugs, and further studies should be conducted on the difference in polysaccharides as well as the biological effects between the two kinds of AR. 25844502 2 57 theme dried 310:314 arg1 root 316:319 the dried root 306:319 the dried root of Astragalus membranaceus var 306:350 The main source of AR in China is the dried root of Astragalus membranaceus var. 25844502 2 57 theme dried 310:314 arg1 source 281:286 The main source 272:286 The main source of AR in China 272:301 The main source of AR in China is the dried root of Astragalus membranaceus var. 25844502 1 58 theme traditional 139:149 arg1 medicine 159:166 traditional chinese medicine 139:166 traditional chinese medicine 139:166 Astragali Radix (AR) is a commonly used herbal drug in traditional chinese medicine and is widely used for the treatment of diabetes, cardiovascular diseases, nephropathy, and neuropathy. 25844502 9 59 dep serum 1097:1101 arg1 the 1093:1095 the 1093:1095 the 1093:1095 However, alterations among the endogenous metabolites in the serum, lung, liver, and spleen were relatively small. 25844502 0 60 theme ¹H 49:50 arg1 Approach 74:81 a ¹H NMR-Based Metabolomic Approach 47:81 a ¹H NMR-Based Metabolomic Approach 47:81 Comparison of Two Different Astragali Radix by a ¹H NMR-Based Metabolomic Approach. 25844502 1 61 theme used 119:122 arg1 Radix 94:98 Astragali Radix 84:98 Astragali Radix (AR) 84:103 Astragali Radix (AR) is a commonly used herbal drug in traditional chinese medicine and is widely used for the treatment of diabetes, cardiovascular diseases, nephropathy, and neuropathy. 25844502 1 61 theme used 119:122 arg1 drug 131:134 a commonly used herbal drug 108:134 a commonly used herbal drug in traditional chinese medicine 108:166 Astragali Radix (AR) is a commonly used herbal drug in traditional chinese medicine and is widely used for the treatment of diabetes, cardiovascular diseases, nephropathy, and neuropathy. 25844502 8 62 theme primary 977:983 arg1 metabolites 985:995 the primary metabolites 973:995 the primary metabolites 973:995 The results showed that SX-AR and GS-AR differed significantly not only in the primary metabolites but also in the secondary metabolites. 25844502 8 63 theme secondary 1013:1021 arg1 metabolites 1023:1033 the secondary metabolites 1009:1033 the secondary metabolites 1009:1033 The results showed that SX-AR and GS-AR differed significantly not only in the primary metabolites but also in the secondary metabolites. 24861346 4 0 theme birchwood 1025:1033 arg1 arabinoxylan 1049:1060 beechwood xylan > birchwood xylan > wheat arabinoxylan 1007:1060 beechwood xylan > birchwood xylan > wheat arabinoxylan 1007:1060 The susceptibilities of different xylosebased polysaccharides to the XylH were assessed to be as follows: oat spelts xylan > beechwood xylan > birchwood xylan > wheat arabinoxylan. 24861346 1 1 dep Microbacterium 290:303 arg1 trichothecenolyticum 305:324 trichothecenolyticum 305:324 trichothecenolyticum 305:324 The XylH gene (1,167-bp) encoding a novel hemicellulase (41,584 Da) was identified from the genome of Microbacterium trichothecenolyticum HY-17, a gastrointestinal bacterium of Gryllotalpa orientalis. 24861346 4 2 theme polysaccharides 928:942 arg1 susceptibilities 886:901 The susceptibilities 882:901 The susceptibilities of different xylosebased polysaccharides to the XylH 882:954 The susceptibilities of different xylosebased polysaccharides to the XylH were assessed to be as follows: oat spelts xylan > beechwood xylan > birchwood xylan > wheat arabinoxylan. 24861346 6 3 theme xylotriose 1348:1357 arg1 composition 1311:1321 the product composition 1299:1321 the product composition of xylobiose (71.2%) and xylotriose (28.8%) as end products 1299:1381 Enzymatic hydrolysis of birchwood xylan resulted in the product composition of xylobiose (71.2%) and xylotriose (28.8%) as end products. 24861346 3 4 theme 5.0-10.0 872:879 arg1 range 863:867 a broad pH range 852:867 a broad pH range of 5.0-10.0 852:879 Unlike other endo-β- 1,4-xylanases from invertebrate-symbiotic bacteria, rXylH was an alkali-tolerant multifunctional enzyme possessing endo-β-1,4-xylanase activity together with β-1,3/β-1,4- glucanase activity, which exhibited its highest xylanolytic activity at pH 9.0 and 60°C, and was relatively stable within a broad pH range of 5.0-10.0. 24861346 0 5 theme trichothecenolyticum 100:119 arg1 HY-17 121:125 Microbacterium trichothecenolyticum HY-17 85:125 Microbacterium trichothecenolyticum HY-17 85:125 Novel alkali-tolerant GH10 endo-β-1,4-xylanase with broad substrate specificity from Microbacterium trichothecenolyticum HY-17, a gut bacterium of the mole cricket Gryllotalpa orientalis. 24861346 4 6 theme xylosebased 916:926 arg1 polysaccharides 928:942 different xylosebased polysaccharides 906:942 different xylosebased polysaccharides 906:942 The susceptibilities of different xylosebased polysaccharides to the XylH were assessed to be as follows: oat spelts xylan > beechwood xylan > birchwood xylan > wheat arabinoxylan. 24861346 5 7 theme p-nitrophenyl 1101:1113 arg1 cellobioside 1121:1132 p-nitrophenyl (pNP) cellobioside 1101:1132 p-nitrophenyl (pNP) cellobioside 1101:1132 rXylH was also able to readily cleave p-nitrophenyl (pNP) cellobioside and pNP-xylopyranoside, but did not hydrolyze other pNP-sugar derivatives, xylobiose, or hexose-based materials. 24861346 4 8 theme spelts 992:997 arg1 xylan 999:1003 oat spelts xylan 988:1003 oat spelts xylan 988:1003 The susceptibilities of different xylosebased polysaccharides to the XylH were assessed to be as follows: oat spelts xylan > beechwood xylan > birchwood xylan > wheat arabinoxylan. 24861346 1 9 theme Gryllotalpa 365:375 arg1 orientalis 377:386 Gryllotalpa orientalis 365:386 Gryllotalpa orientalis 365:386 The XylH gene (1,167-bp) encoding a novel hemicellulase (41,584 Da) was identified from the genome of Microbacterium trichothecenolyticum HY-17, a gastrointestinal bacterium of Gryllotalpa orientalis. 24861346 6 10 theme xylobiose 1326:1334 arg1 composition 1311:1321 the product composition 1299:1321 the product composition of xylobiose (71.2%) and xylotriose (28.8%) as end products 1299:1381 Enzymatic hydrolysis of birchwood xylan resulted in the product composition of xylobiose (71.2%) and xylotriose (28.8%) as end products. 24861346 3 11 theme other 545:549 arg1 1,4-xylanases 559:571 other endo-β- 1,4-xylanases 545:571 other endo-β- 1,4-xylanases from invertebrate-symbiotic bacteria 545:608 Unlike other endo-β- 1,4-xylanases from invertebrate-symbiotic bacteria, rXylH was an alkali-tolerant multifunctional enzyme possessing endo-β-1,4-xylanase activity together with β-1,3/β-1,4- glucanase activity, which exhibited its highest xylanolytic activity at pH 9.0 and 60°C, and was relatively stable within a broad pH range of 5.0-10.0. 24861346 3 12 theme invertebrate-symbiotic 578:599 arg1 bacteria 601:608 invertebrate-symbiotic bacteria 578:608 invertebrate-symbiotic bacteria 578:608 Unlike other endo-β- 1,4-xylanases from invertebrate-symbiotic bacteria, rXylH was an alkali-tolerant multifunctional enzyme possessing endo-β-1,4-xylanase activity together with β-1,3/β-1,4- glucanase activity, which exhibited its highest xylanolytic activity at pH 9.0 and 60°C, and was relatively stable within a broad pH range of 5.0-10.0. 24861346 1 13 theme orientalis 377:386 arg1 HY-17 326:330 Microbacterium trichothecenolyticum HY-17 290:330 Microbacterium trichothecenolyticum HY-17 290:330 The XylH gene (1,167-bp) encoding a novel hemicellulase (41,584 Da) was identified from the genome of Microbacterium trichothecenolyticum HY-17, a gastrointestinal bacterium of Gryllotalpa orientalis. 24861346 1 13 theme orientalis 377:386 arg1 bacterium 352:360 a gastrointestinal bacterium 333:360 a gastrointestinal bacterium of Gryllotalpa orientalis 333:386 The XylH gene (1,167-bp) encoding a novel hemicellulase (41,584 Da) was identified from the genome of Microbacterium trichothecenolyticum HY-17, a gastrointestinal bacterium of Gryllotalpa orientalis. 24861346 5 14 theme pNP-sugar 1186:1194 arg1 derivatives 1196:1206 other pNP-sugar derivatives 1180:1206 other pNP-sugar derivatives 1180:1206 rXylH was also able to readily cleave p-nitrophenyl (pNP) cellobioside and pNP-xylopyranoside, but did not hydrolyze other pNP-sugar derivatives, xylobiose, or hexose-based materials. 24861346 3 15 theme endo-β- 551:557 arg1 1,4-xylanases 559:571 other endo-β- 1,4-xylanases 545:571 other endo-β- 1,4-xylanases from invertebrate-symbiotic bacteria 545:608 Unlike other endo-β- 1,4-xylanases from invertebrate-symbiotic bacteria, rXylH was an alkali-tolerant multifunctional enzyme possessing endo-β-1,4-xylanase activity together with β-1,3/β-1,4- glucanase activity, which exhibited its highest xylanolytic activity at pH 9.0 and 60°C, and was relatively stable within a broad pH range of 5.0-10.0. 24861346 4 16 theme xylan 1035:1039 arg1 arabinoxylan 1049:1060 beechwood xylan > birchwood xylan > wheat arabinoxylan 1007:1060 beechwood xylan > birchwood xylan > wheat arabinoxylan 1007:1060 The susceptibilities of different xylosebased polysaccharides to the XylH were assessed to be as follows: oat spelts xylan > beechwood xylan > birchwood xylan > wheat arabinoxylan. 24861346 2 17 theme Isoptericola 509:520 arg1 variabilis 522:531 Isoptericola variabilis 225 509:535 Isoptericola variabilis 225 509:535 The enzyme consisted of a single catalytic domain, which is 74% identical to that of an endo-β-1,4-xylanase (GH10) from Isoptericola variabilis 225. 24861346 6 18 theme product 1303:1309 arg1 composition 1311:1321 the product composition 1299:1321 the product composition of xylobiose (71.2%) and xylotriose (28.8%) as end products 1299:1381 Enzymatic hydrolysis of birchwood xylan resulted in the product composition of xylobiose (71.2%) and xylotriose (28.8%) as end products. 24861346 1 19 theme XylH 192:195 arg1 gene 197:200 The XylH gene 188:200 The XylH gene (1,167-bp) encoding a novel hemicellulase (41,584 Da) 188:254 The XylH gene (1,167-bp) encoding a novel hemicellulase (41,584 Da) was identified from the genome of Microbacterium trichothecenolyticum HY-17, a gastrointestinal bacterium of Gryllotalpa orientalis. 24861346 0 20 theme gut 130:132 arg1 endo-β-1,4-xylanase 27:45 Novel alkali-tolerant GH10 endo-β-1,4-xylanase 0:45 Novel alkali-tolerant GH10 endo-β-1,4-xylanase with broad substrate specificity from Microbacterium trichothecenolyticum HY-17 0:125 Novel alkali-tolerant GH10 endo-β-1,4-xylanase with broad substrate specificity from Microbacterium trichothecenolyticum HY-17, a gut bacterium of the mole cricket Gryllotalpa orientalis. 24861346 0 20 theme gut 130:132 arg1 bacterium 134:142 a gut bacterium 128:142 a gut bacterium of the mole cricket Gryllotalpa orientalis 128:185 Novel alkali-tolerant GH10 endo-β-1,4-xylanase with broad substrate specificity from Microbacterium trichothecenolyticum HY-17, a gut bacterium of the mole cricket Gryllotalpa orientalis. 24861346 3 21 theme xylanolytic 778:788 arg1 activity 790:797 its highest xylanolytic activity 766:797 its highest xylanolytic activity 766:797 Unlike other endo-β- 1,4-xylanases from invertebrate-symbiotic bacteria, rXylH was an alkali-tolerant multifunctional enzyme possessing endo-β-1,4-xylanase activity together with β-1,3/β-1,4- glucanase activity, which exhibited its highest xylanolytic activity at pH 9.0 and 60°C, and was relatively stable within a broad pH range of 5.0-10.0. 24861346 4 22 theme > 1041:1041 arg1 arabinoxylan 1049:1060 beechwood xylan > birchwood xylan > wheat arabinoxylan 1007:1060 beechwood xylan > birchwood xylan > wheat arabinoxylan 1007:1060 The susceptibilities of different xylosebased polysaccharides to the XylH were assessed to be as follows: oat spelts xylan > beechwood xylan > birchwood xylan > wheat arabinoxylan. 24861346 6 23 theme end 1370:1372 arg1 products 1374:1381 end products 1370:1381 end products 1370:1381 Enzymatic hydrolysis of birchwood xylan resulted in the product composition of xylobiose (71.2%) and xylotriose (28.8%) as end products. 24861346 0 24 theme alkali-tolerant 6:20 arg1 endo-β-1,4-xylanase 27:45 Novel alkali-tolerant GH10 endo-β-1,4-xylanase 0:45 Novel alkali-tolerant GH10 endo-β-1,4-xylanase with broad substrate specificity from Microbacterium trichothecenolyticum HY-17 0:125 Novel alkali-tolerant GH10 endo-β-1,4-xylanase with broad substrate specificity from Microbacterium trichothecenolyticum HY-17, a gut bacterium of the mole cricket Gryllotalpa orientalis. 24861346 0 24 theme alkali-tolerant 6:20 arg1 bacterium 134:142 a gut bacterium 128:142 a gut bacterium of the mole cricket Gryllotalpa orientalis 128:185 Novel alkali-tolerant GH10 endo-β-1,4-xylanase with broad substrate specificity from Microbacterium trichothecenolyticum HY-17, a gut bacterium of the mole cricket Gryllotalpa orientalis. 24861346 4 25 theme > 1023:1023 arg1 arabinoxylan 1049:1060 beechwood xylan > birchwood xylan > wheat arabinoxylan 1007:1060 beechwood xylan > birchwood xylan > wheat arabinoxylan 1007:1060 The susceptibilities of different xylosebased polysaccharides to the XylH were assessed to be as follows: oat spelts xylan > beechwood xylan > birchwood xylan > wheat arabinoxylan. 24861346 4 26 theme different 906:914 arg1 polysaccharides 928:942 different xylosebased polysaccharides 906:942 different xylosebased polysaccharides 906:942 The susceptibilities of different xylosebased polysaccharides to the XylH were assessed to be as follows: oat spelts xylan > beechwood xylan > birchwood xylan > wheat arabinoxylan. 24861346 4 27 theme xylan 1017:1021 arg1 arabinoxylan 1049:1060 beechwood xylan > birchwood xylan > wheat arabinoxylan 1007:1060 beechwood xylan > birchwood xylan > wheat arabinoxylan 1007:1060 The susceptibilities of different xylosebased polysaccharides to the XylH were assessed to be as follows: oat spelts xylan > beechwood xylan > birchwood xylan > wheat arabinoxylan. 24861346 3 28 theme glucanase 730:738 arg1 activity 740:747 β-1,3/β-1,4- glucanase activity 717:747 β-1,3/β-1,4- glucanase activity 717:747 Unlike other endo-β- 1,4-xylanases from invertebrate-symbiotic bacteria, rXylH was an alkali-tolerant multifunctional enzyme possessing endo-β-1,4-xylanase activity together with β-1,3/β-1,4- glucanase activity, which exhibited its highest xylanolytic activity at pH 9.0 and 60°C, and was relatively stable within a broad pH range of 5.0-10.0. 24861346 0 29 theme Novel 0:4 arg1 endo-β-1,4-xylanase 27:45 Novel alkali-tolerant GH10 endo-β-1,4-xylanase 0:45 Novel alkali-tolerant GH10 endo-β-1,4-xylanase with broad substrate specificity from Microbacterium trichothecenolyticum HY-17 0:125 Novel alkali-tolerant GH10 endo-β-1,4-xylanase with broad substrate specificity from Microbacterium trichothecenolyticum HY-17, a gut bacterium of the mole cricket Gryllotalpa orientalis. 24861346 0 29 theme Novel 0:4 arg1 bacterium 134:142 a gut bacterium 128:142 a gut bacterium of the mole cricket Gryllotalpa orientalis 128:185 Novel alkali-tolerant GH10 endo-β-1,4-xylanase with broad substrate specificity from Microbacterium trichothecenolyticum HY-17, a gut bacterium of the mole cricket Gryllotalpa orientalis. 24861346 2 30 from variabilis 522:531 arg1 GH10 498:501 GH10 498:501 GH10 498:501 The enzyme consisted of a single catalytic domain, which is 74% identical to that of an endo-β-1,4-xylanase (GH10) from Isoptericola variabilis 225. 24861346 2 30 from variabilis 522:531 arg1 endo-β-1,4-xylanase 477:495 an endo-β-1,4-xylanase 474:495 an endo-β-1,4-xylanase (GH10) from Isoptericola variabilis 225 474:535 The enzyme consisted of a single catalytic domain, which is 74% identical to that of an endo-β-1,4-xylanase (GH10) from Isoptericola variabilis 225. 24861346 0 31 theme GH10 22:25 arg1 endo-β-1,4-xylanase 27:45 Novel alkali-tolerant GH10 endo-β-1,4-xylanase 0:45 Novel alkali-tolerant GH10 endo-β-1,4-xylanase with broad substrate specificity from Microbacterium trichothecenolyticum HY-17 0:125 Novel alkali-tolerant GH10 endo-β-1,4-xylanase with broad substrate specificity from Microbacterium trichothecenolyticum HY-17, a gut bacterium of the mole cricket Gryllotalpa orientalis. 24861346 0 31 theme GH10 22:25 arg1 bacterium 134:142 a gut bacterium 128:142 a gut bacterium of the mole cricket Gryllotalpa orientalis 128:185 Novel alkali-tolerant GH10 endo-β-1,4-xylanase with broad substrate specificity from Microbacterium trichothecenolyticum HY-17, a gut bacterium of the mole cricket Gryllotalpa orientalis. 24861346 0 32 from HY-17 121:125 arg1 endo-β-1,4-xylanase 27:45 Novel alkali-tolerant GH10 endo-β-1,4-xylanase 0:45 Novel alkali-tolerant GH10 endo-β-1,4-xylanase with broad substrate specificity from Microbacterium trichothecenolyticum HY-17 0:125 Novel alkali-tolerant GH10 endo-β-1,4-xylanase with broad substrate specificity from Microbacterium trichothecenolyticum HY-17, a gut bacterium of the mole cricket Gryllotalpa orientalis. 24861346 0 32 from HY-17 121:125 arg1 bacterium 134:142 a gut bacterium 128:142 a gut bacterium of the mole cricket Gryllotalpa orientalis 128:185 Novel alkali-tolerant GH10 endo-β-1,4-xylanase with broad substrate specificity from Microbacterium trichothecenolyticum HY-17, a gut bacterium of the mole cricket Gryllotalpa orientalis. 24861346 0 33 theme broad 52:56 arg1 specificity 68:78 broad substrate specificity 52:78 broad substrate specificity 52:78 Novel alkali-tolerant GH10 endo-β-1,4-xylanase with broad substrate specificity from Microbacterium trichothecenolyticum HY-17, a gut bacterium of the mole cricket Gryllotalpa orientalis. 24861346 1 34 theme Microbacterium 290:303 arg1 HY-17 326:330 Microbacterium trichothecenolyticum HY-17 290:330 Microbacterium trichothecenolyticum HY-17 290:330 The XylH gene (1,167-bp) encoding a novel hemicellulase (41,584 Da) was identified from the genome of Microbacterium trichothecenolyticum HY-17, a gastrointestinal bacterium of Gryllotalpa orientalis. 24861346 1 34 theme Microbacterium 290:303 arg1 bacterium 352:360 a gastrointestinal bacterium 333:360 a gastrointestinal bacterium of Gryllotalpa orientalis 333:386 The XylH gene (1,167-bp) encoding a novel hemicellulase (41,584 Da) was identified from the genome of Microbacterium trichothecenolyticum HY-17, a gastrointestinal bacterium of Gryllotalpa orientalis. 24861346 0 35 theme cricket 156:162 arg1 orientalis 176:185 the mole cricket Gryllotalpa orientalis 147:185 the mole cricket Gryllotalpa orientalis 147:185 Novel alkali-tolerant GH10 endo-β-1,4-xylanase with broad substrate specificity from Microbacterium trichothecenolyticum HY-17, a gut bacterium of the mole cricket Gryllotalpa orientalis. 24861346 3 36 dep enzyme 656:661 arg1 exhibited 756:764 exhibited 756:764 exhibited its highest xylanolytic activity at pH 9.0 and 60°C 756:816 Unlike other endo-β- 1,4-xylanases from invertebrate-symbiotic bacteria, rXylH was an alkali-tolerant multifunctional enzyme possessing endo-β-1,4-xylanase activity together with β-1,3/β-1,4- glucanase activity, which exhibited its highest xylanolytic activity at pH 9.0 and 60°C, and was relatively stable within a broad pH range of 5.0-10.0. 24861346 3 36 dep enzyme 656:661 arg1 stable 838:843 stable 838:843 stable 838:843 Unlike other endo-β- 1,4-xylanases from invertebrate-symbiotic bacteria, rXylH was an alkali-tolerant multifunctional enzyme possessing endo-β-1,4-xylanase activity together with β-1,3/β-1,4- glucanase activity, which exhibited its highest xylanolytic activity at pH 9.0 and 60°C, and was relatively stable within a broad pH range of 5.0-10.0. 24861346 2 37 theme single 415:420 arg1 domain 432:437 a single catalytic domain 413:437 a single catalytic domain 413:437 The enzyme consisted of a single catalytic domain, which is 74% identical to that of an endo-β-1,4-xylanase (GH10) from Isoptericola variabilis 225. 24861346 2 37 theme single 415:420 arg1 identical 453:461 identical 453:461 identical 453:461 The enzyme consisted of a single catalytic domain, which is 74% identical to that of an endo-β-1,4-xylanase (GH10) from Isoptericola variabilis 225. 24861346 4 38 theme wheat 1043:1047 arg1 arabinoxylan 1049:1060 beechwood xylan > birchwood xylan > wheat arabinoxylan 1007:1060 beechwood xylan > birchwood xylan > wheat arabinoxylan 1007:1060 The susceptibilities of different xylosebased polysaccharides to the XylH were assessed to be as follows: oat spelts xylan > beechwood xylan > birchwood xylan > wheat arabinoxylan. 24861346 0 39 theme mole 151:154 arg1 orientalis 176:185 the mole cricket Gryllotalpa orientalis 147:185 the mole cricket Gryllotalpa orientalis 147:185 Novel alkali-tolerant GH10 endo-β-1,4-xylanase with broad substrate specificity from Microbacterium trichothecenolyticum HY-17, a gut bacterium of the mole cricket Gryllotalpa orientalis. 24861346 3 40 theme endo-β-1,4-xylanase 674:692 arg1 activity 694:701 endo-β-1,4-xylanase activity 674:701 endo-β-1,4-xylanase activity 674:701 Unlike other endo-β- 1,4-xylanases from invertebrate-symbiotic bacteria, rXylH was an alkali-tolerant multifunctional enzyme possessing endo-β-1,4-xylanase activity together with β-1,3/β-1,4- glucanase activity, which exhibited its highest xylanolytic activity at pH 9.0 and 60°C, and was relatively stable within a broad pH range of 5.0-10.0. 24861346 6 41 theme xylan 1281:1285 arg1 hydrolysis 1257:1266 Enzymatic hydrolysis 1247:1266 Enzymatic hydrolysis of birchwood xylan 1247:1285 Enzymatic hydrolysis of birchwood xylan resulted in the product composition of xylobiose (71.2%) and xylotriose (28.8%) as end products. 24861346 0 42 with endo-β-1,4-xylanase 27:45 arg1 specificity 68:78 broad substrate specificity 52:78 broad substrate specificity 52:78 Novel alkali-tolerant GH10 endo-β-1,4-xylanase with broad substrate specificity from Microbacterium trichothecenolyticum HY-17, a gut bacterium of the mole cricket Gryllotalpa orientalis. 24861346 1 43 theme novel 224:228 arg1 hemicellulase 230:242 a novel hemicellulase 222:242 a novel hemicellulase (41,584 Da) 222:254 The XylH gene (1,167-bp) encoding a novel hemicellulase (41,584 Da) was identified from the genome of Microbacterium trichothecenolyticum HY-17, a gastrointestinal bacterium of Gryllotalpa orientalis. 24861346 1 43 theme novel 224:228 arg1 Da 252:253 41,584 Da 245:253 41,584 Da 245:253 The XylH gene (1,167-bp) encoding a novel hemicellulase (41,584 Da) was identified from the genome of Microbacterium trichothecenolyticum HY-17, a gastrointestinal bacterium of Gryllotalpa orientalis. 24861346 1 44 theme HY-17 326:330 arg1 genome 280:285 the genome 276:285 the genome of Microbacterium trichothecenolyticum HY-17, a gastrointestinal bacterium of Gryllotalpa orientalis 276:386 The XylH gene (1,167-bp) encoding a novel hemicellulase (41,584 Da) was identified from the genome of Microbacterium trichothecenolyticum HY-17, a gastrointestinal bacterium of Gryllotalpa orientalis. 24861346 0 45 theme orientalis 176:185 arg1 endo-β-1,4-xylanase 27:45 Novel alkali-tolerant GH10 endo-β-1,4-xylanase 0:45 Novel alkali-tolerant GH10 endo-β-1,4-xylanase with broad substrate specificity from Microbacterium trichothecenolyticum HY-17 0:125 Novel alkali-tolerant GH10 endo-β-1,4-xylanase with broad substrate specificity from Microbacterium trichothecenolyticum HY-17, a gut bacterium of the mole cricket Gryllotalpa orientalis. 24861346 0 45 theme orientalis 176:185 arg1 bacterium 134:142 a gut bacterium 128:142 a gut bacterium of the mole cricket Gryllotalpa orientalis 128:185 Novel alkali-tolerant GH10 endo-β-1,4-xylanase with broad substrate specificity from Microbacterium trichothecenolyticum HY-17, a gut bacterium of the mole cricket Gryllotalpa orientalis. 24861346 6 46 theme birchwood 1271:1279 arg1 xylan 1281:1285 birchwood xylan 1271:1285 birchwood xylan 1271:1285 Enzymatic hydrolysis of birchwood xylan resulted in the product composition of xylobiose (71.2%) and xylotriose (28.8%) as end products. 24861346 0 47 theme substrate 58:66 arg1 specificity 68:78 broad substrate specificity 52:78 broad substrate specificity 52:78 Novel alkali-tolerant GH10 endo-β-1,4-xylanase with broad substrate specificity from Microbacterium trichothecenolyticum HY-17, a gut bacterium of the mole cricket Gryllotalpa orientalis. 24861346 5 48 theme hexose-based 1223:1234 arg1 materials 1236:1244 hexose-based materials 1223:1244 hexose-based materials 1223:1244 rXylH was also able to readily cleave p-nitrophenyl (pNP) cellobioside and pNP-xylopyranoside, but did not hydrolyze other pNP-sugar derivatives, xylobiose, or hexose-based materials. 24861346 0 49 theme Gryllotalpa 164:174 arg1 orientalis 176:185 the mole cricket Gryllotalpa orientalis 147:185 the mole cricket Gryllotalpa orientalis 147:185 Novel alkali-tolerant GH10 endo-β-1,4-xylanase with broad substrate specificity from Microbacterium trichothecenolyticum HY-17, a gut bacterium of the mole cricket Gryllotalpa orientalis. 24861346 1 50 dep gene 197:200 arg1 1,167-bp 203:210 1,167-bp 203:210 1,167-bp 203:210 The XylH gene (1,167-bp) encoding a novel hemicellulase (41,584 Da) was identified from the genome of Microbacterium trichothecenolyticum HY-17, a gastrointestinal bacterium of Gryllotalpa orientalis. 24861346 5 51 theme other 1180:1184 arg1 derivatives 1196:1206 other pNP-sugar derivatives 1180:1206 other pNP-sugar derivatives 1180:1206 rXylH was also able to readily cleave p-nitrophenyl (pNP) cellobioside and pNP-xylopyranoside, but did not hydrolyze other pNP-sugar derivatives, xylobiose, or hexose-based materials. 24861346 3 52 theme broad 854:858 arg1 range 863:867 a broad pH range 852:867 a broad pH range of 5.0-10.0 852:879 Unlike other endo-β- 1,4-xylanases from invertebrate-symbiotic bacteria, rXylH was an alkali-tolerant multifunctional enzyme possessing endo-β-1,4-xylanase activity together with β-1,3/β-1,4- glucanase activity, which exhibited its highest xylanolytic activity at pH 9.0 and 60°C, and was relatively stable within a broad pH range of 5.0-10.0. 24861346 3 53 theme β-1,3/β-1,4- 717:728 arg1 activity 740:747 β-1,3/β-1,4- glucanase activity 717:747 β-1,3/β-1,4- glucanase activity 717:747 Unlike other endo-β- 1,4-xylanases from invertebrate-symbiotic bacteria, rXylH was an alkali-tolerant multifunctional enzyme possessing endo-β-1,4-xylanase activity together with β-1,3/β-1,4- glucanase activity, which exhibited its highest xylanolytic activity at pH 9.0 and 60°C, and was relatively stable within a broad pH range of 5.0-10.0. 24861346 6 54 theme Enzymatic 1247:1255 arg1 hydrolysis 1257:1266 Enzymatic hydrolysis 1247:1266 Enzymatic hydrolysis of birchwood xylan 1247:1285 Enzymatic hydrolysis of birchwood xylan resulted in the product composition of xylobiose (71.2%) and xylotriose (28.8%) as end products. 24861346 3 55 theme pH 860:861 arg1 range 863:867 a broad pH range 852:867 a broad pH range of 5.0-10.0 852:879 Unlike other endo-β- 1,4-xylanases from invertebrate-symbiotic bacteria, rXylH was an alkali-tolerant multifunctional enzyme possessing endo-β-1,4-xylanase activity together with β-1,3/β-1,4- glucanase activity, which exhibited its highest xylanolytic activity at pH 9.0 and 60°C, and was relatively stable within a broad pH range of 5.0-10.0. 24861346 0 56 theme Microbacterium 85:98 arg1 HY-17 121:125 Microbacterium trichothecenolyticum HY-17 85:125 Microbacterium trichothecenolyticum HY-17 85:125 Novel alkali-tolerant GH10 endo-β-1,4-xylanase with broad substrate specificity from Microbacterium trichothecenolyticum HY-17, a gut bacterium of the mole cricket Gryllotalpa orientalis. 24861346 2 57 theme catalytic 422:430 arg1 domain 432:437 a single catalytic domain 413:437 a single catalytic domain 413:437 The enzyme consisted of a single catalytic domain, which is 74% identical to that of an endo-β-1,4-xylanase (GH10) from Isoptericola variabilis 225. 24861346 2 57 theme catalytic 422:430 arg1 identical 453:461 identical 453:461 identical 453:461 The enzyme consisted of a single catalytic domain, which is 74% identical to that of an endo-β-1,4-xylanase (GH10) from Isoptericola variabilis 225. 24861346 3 58 theme alkali-tolerant 624:638 arg1 enzyme 656:661 an alkali-tolerant multifunctional enzyme 621:661 an alkali-tolerant multifunctional enzyme possessing endo-β-1,4-xylanase activity 621:701 Unlike other endo-β- 1,4-xylanases from invertebrate-symbiotic bacteria, rXylH was an alkali-tolerant multifunctional enzyme possessing endo-β-1,4-xylanase activity together with β-1,3/β-1,4- glucanase activity, which exhibited its highest xylanolytic activity at pH 9.0 and 60°C, and was relatively stable within a broad pH range of 5.0-10.0. 24861346 3 58 theme alkali-tolerant 624:638 arg1 rXylH 611:615 rXylH 611:615 rXylH 611:615 Unlike other endo-β- 1,4-xylanases from invertebrate-symbiotic bacteria, rXylH was an alkali-tolerant multifunctional enzyme possessing endo-β-1,4-xylanase activity together with β-1,3/β-1,4- glucanase activity, which exhibited its highest xylanolytic activity at pH 9.0 and 60°C, and was relatively stable within a broad pH range of 5.0-10.0. 24861346 3 59 from bacteria 601:608 arg1 1,4-xylanases 559:571 other endo-β- 1,4-xylanases 545:571 other endo-β- 1,4-xylanases from invertebrate-symbiotic bacteria 545:608 Unlike other endo-β- 1,4-xylanases from invertebrate-symbiotic bacteria, rXylH was an alkali-tolerant multifunctional enzyme possessing endo-β-1,4-xylanase activity together with β-1,3/β-1,4- glucanase activity, which exhibited its highest xylanolytic activity at pH 9.0 and 60°C, and was relatively stable within a broad pH range of 5.0-10.0. 24861346 3 60 contain possessing 663:672 arg1 enzyme 656:661 an alkali-tolerant multifunctional enzyme 621:661 an alkali-tolerant multifunctional enzyme possessing endo-β-1,4-xylanase activity 621:701 Unlike other endo-β- 1,4-xylanases from invertebrate-symbiotic bacteria, rXylH was an alkali-tolerant multifunctional enzyme possessing endo-β-1,4-xylanase activity together with β-1,3/β-1,4- glucanase activity, which exhibited its highest xylanolytic activity at pH 9.0 and 60°C, and was relatively stable within a broad pH range of 5.0-10.0. 24861346 3 60 contain possessing 663:672 arg1 rXylH 611:615 rXylH 611:615 rXylH 611:615 Unlike other endo-β- 1,4-xylanases from invertebrate-symbiotic bacteria, rXylH was an alkali-tolerant multifunctional enzyme possessing endo-β-1,4-xylanase activity together with β-1,3/β-1,4- glucanase activity, which exhibited its highest xylanolytic activity at pH 9.0 and 60°C, and was relatively stable within a broad pH range of 5.0-10.0. 24861346 3 60 contain possessing 663:672 arg2 activity 694:701 endo-β-1,4-xylanase activity 674:701 endo-β-1,4-xylanase activity 674:701 Unlike other endo-β- 1,4-xylanases from invertebrate-symbiotic bacteria, rXylH was an alkali-tolerant multifunctional enzyme possessing endo-β-1,4-xylanase activity together with β-1,3/β-1,4- glucanase activity, which exhibited its highest xylanolytic activity at pH 9.0 and 60°C, and was relatively stable within a broad pH range of 5.0-10.0. 24861346 4 61 theme beechwood 1007:1015 arg1 arabinoxylan 1049:1060 beechwood xylan > birchwood xylan > wheat arabinoxylan 1007:1060 beechwood xylan > birchwood xylan > wheat arabinoxylan 1007:1060 The susceptibilities of different xylosebased polysaccharides to the XylH were assessed to be as follows: oat spelts xylan > beechwood xylan > birchwood xylan > wheat arabinoxylan. 24861346 1 62 theme gastrointestinal 335:350 arg1 HY-17 326:330 Microbacterium trichothecenolyticum HY-17 290:330 Microbacterium trichothecenolyticum HY-17 290:330 The XylH gene (1,167-bp) encoding a novel hemicellulase (41,584 Da) was identified from the genome of Microbacterium trichothecenolyticum HY-17, a gastrointestinal bacterium of Gryllotalpa orientalis. 24861346 1 62 theme gastrointestinal 335:350 arg1 bacterium 352:360 a gastrointestinal bacterium 333:360 a gastrointestinal bacterium of Gryllotalpa orientalis 333:386 The XylH gene (1,167-bp) encoding a novel hemicellulase (41,584 Da) was identified from the genome of Microbacterium trichothecenolyticum HY-17, a gastrointestinal bacterium of Gryllotalpa orientalis. 24861346 3 63 theme multifunctional 640:654 arg1 enzyme 656:661 an alkali-tolerant multifunctional enzyme 621:661 an alkali-tolerant multifunctional enzyme possessing endo-β-1,4-xylanase activity 621:701 Unlike other endo-β- 1,4-xylanases from invertebrate-symbiotic bacteria, rXylH was an alkali-tolerant multifunctional enzyme possessing endo-β-1,4-xylanase activity together with β-1,3/β-1,4- glucanase activity, which exhibited its highest xylanolytic activity at pH 9.0 and 60°C, and was relatively stable within a broad pH range of 5.0-10.0. 24861346 3 63 theme multifunctional 640:654 arg1 rXylH 611:615 rXylH 611:615 rXylH 611:615 Unlike other endo-β- 1,4-xylanases from invertebrate-symbiotic bacteria, rXylH was an alkali-tolerant multifunctional enzyme possessing endo-β-1,4-xylanase activity together with β-1,3/β-1,4- glucanase activity, which exhibited its highest xylanolytic activity at pH 9.0 and 60°C, and was relatively stable within a broad pH range of 5.0-10.0. 24861346 3 64 theme highest 770:776 arg1 activity 790:797 its highest xylanolytic activity 766:797 its highest xylanolytic activity 766:797 Unlike other endo-β- 1,4-xylanases from invertebrate-symbiotic bacteria, rXylH was an alkali-tolerant multifunctional enzyme possessing endo-β-1,4-xylanase activity together with β-1,3/β-1,4- glucanase activity, which exhibited its highest xylanolytic activity at pH 9.0 and 60°C, and was relatively stable within a broad pH range of 5.0-10.0. 24861346 4 65 theme oat 988:990 arg1 xylan 999:1003 oat spelts xylan 988:1003 oat spelts xylan 988:1003 The susceptibilities of different xylosebased polysaccharides to the XylH were assessed to be as follows: oat spelts xylan > beechwood xylan > birchwood xylan > wheat arabinoxylan. 24708722 12 0 theme pure 1894:1897 arg1 hydrolases 1908:1917 pure glycosyl hydrolases 1894:1917 pure glycosyl hydrolases 1894:1917 Based on experiments with optimized cocktails of pure glycosyl hydrolases, enzyme imbalance probably accounted for much of the lower yields. 24708722 9 1 theme dry 1520:1522 arg1 basis 1531:1535 a dry weight basis 1518:1535 a dry weight basis compared to 39.2% for corn stover 1518:1569 All of the forbs had lower total glucose (Glc) content from all sources (cell walls, sucrose, starch, glucosides, and free Glc) compared to corn stover (range 16.2 to 23.0% on a dry weight basis compared to 39.2% for corn stover). 24708722 9 2 contain had 1359:1361 arg1 forbs 1353:1357 the forbs 1349:1357 the forbs 1349:1357 All of the forbs had lower total glucose (Glc) content from all sources (cell walls, sucrose, starch, glucosides, and free Glc) compared to corn stover (range 16.2 to 23.0% on a dry weight basis compared to 39.2% for corn stover). 24708722 9 2 contain had 1359:1361 arg2 content 1389:1395 lower total glucose (Glc) content 1363:1395 lower total glucose (Glc) content from all sources (cell walls, sucrose, starch, glucosides, and free Glc) 1363:1468 All of the forbs had lower total glucose (Glc) content from all sources (cell walls, sucrose, starch, glucosides, and free Glc) compared to corn stover (range 16.2 to 23.0% on a dry weight basis compared to 39.2% for corn stover). 24708722 9 2 contain had 1359:1361 arg1 All 1342:1344 All 1342:1344 All 1342:1344 All of the forbs had lower total glucose (Glc) content from all sources (cell walls, sucrose, starch, glucosides, and free Glc) compared to corn stover (range 16.2 to 23.0% on a dry weight basis compared to 39.2% for corn stover). 24708722 3 3 theme reduced 527:533 arg1 competition 535:545 reduced competition 527:545 reduced competition with food production 527:566 The use of old fields, restored prairie, or marginal lands to grow biofuel feedstocks offers several potential benefits including minimal agronomic inputs, reduced competition with food production, and high biodiversity. 24708722 9 4 theme total 1369:1373 arg1 content 1389:1395 lower total glucose (Glc) content 1363:1395 lower total glucose (Glc) content from all sources (cell walls, sucrose, starch, glucosides, and free Glc) 1363:1468 All of the forbs had lower total glucose (Glc) content from all sources (cell walls, sucrose, starch, glucosides, and free Glc) compared to corn stover (range 16.2 to 23.0% on a dry weight basis compared to 39.2% for corn stover). 24708722 6 5 theme sugars 922:927 arg1 yield 901:905 the yield 897:905 the yield of fermentable sugars from four representative forbs 897:958 RESULTS The factors that contribute to the yield of fermentable sugars from four representative forbs were studied in comparison with corn stover. 24708722 2 6 theme agronomic 302:310 arg1 conditions 331:340 economic, agronomic, and environmental conditions 292:340 economic, agronomic, and environmental conditions 292:340 The best choice under any particular combination of economic, agronomic, and environmental conditions depends on multiple factors. 24708722 13 7 theme xyloglucanase 1998:2010 arg1 Addition 1986:1993 Addition 1986:1993 Addition of xyloglucanase and α-xylosidase, two enzymes targeting Glc-containing polysaccharides that are more abundant in dicotyledonous plants compared to grasses, 1986:2150 Addition of xyloglucanase and α-xylosidase, two enzymes targeting Glc-containing polysaccharides that are more abundant in dicotyledonous plants compared to grasses, enhanced Glc yields from lamb's quarters, but Glc yields were still lower than from corn stover. 24708722 2 8 theme economic 292:299 arg1 conditions 331:340 economic, agronomic, and environmental conditions 292:340 economic, agronomic, and environmental conditions 292:340 The best choice under any particular combination of economic, agronomic, and environmental conditions depends on multiple factors. 24708722 15 9 theme wall 2491:2494 arg1 composition 2496:2506 the different cell wall composition 2472:2506 the different cell wall composition of forbs 2472:2515 Furthermore, new enzyme mixtures tailored to the different cell wall composition of forbs will have to be developed. 24708722 13 10 theme Glc 2198:2200 arg1 yields 2202:2207 Glc yields 2198:2207 Glc yields 2198:2207 Addition of xyloglucanase and α-xylosidase, two enzymes targeting Glc-containing polysaccharides that are more abundant in dicotyledonous plants compared to grasses, enhanced Glc yields from lamb's quarters, but Glc yields were still lower than from corn stover. 24708722 14 11 theme biofuel 2320:2326 arg1 feedstocks 2328:2337 biofuel feedstocks 2320:2337 biofuel feedstocks 2320:2337 CONCLUSION The potential utilization of forb-rich plant communities as biofuel feedstocks must take into account their lower Glc content compared to grasses such as corn stover. 24708722 3 12 with inputs 519:524 arg1 production 557:566 food production 552:566 food production 552:566 The use of old fields, restored prairie, or marginal lands to grow biofuel feedstocks offers several potential benefits including minimal agronomic inputs, reduced competition with food production, and high biodiversity. 24708722 2 13 theme conditions 331:340 arg1 combination 277:287 any particular combination 262:287 any particular combination of economic, agronomic, and environmental conditions 262:340 The best choice under any particular combination of economic, agronomic, and environmental conditions depends on multiple factors. 24708722 15 14 theme different 2476:2484 arg1 composition 2496:2506 the different cell wall composition 2472:2506 the different cell wall composition of forbs 2472:2515 Furthermore, new enzyme mixtures tailored to the different cell wall composition of forbs will have to be developed. 24708722 1 15 theme biofuels 199:206 arg1 production 185:194 the practical production 171:194 the practical production of biofuels from lignocellulosic materials 171:237 BACKGROUND Many different feedstocks are under consideration for the practical production of biofuels from lignocellulosic materials. 24708722 6 16 theme corn 992:995 arg1 stover 997:1002 corn stover 992:1002 corn stover 992:1002 RESULTS The factors that contribute to the yield of fermentable sugars from four representative forbs were studied in comparison with corn stover. 24708722 9 17 theme corn 1559:1562 arg1 stover 1564:1569 corn stover 1559:1569 corn stover 1559:1569 All of the forbs had lower total glucose (Glc) content from all sources (cell walls, sucrose, starch, glucosides, and free Glc) compared to corn stover (range 16.2 to 23.0% on a dry weight basis compared to 39.2% for corn stover). 24708722 10 18 theme Glc 1658:1660 arg1 yields 1648:1653 yields 1648:1653 yields of Glc as a percentage of total Glc 1648:1689 When digested with commercial enzyme mixtures after alkaline pretreatment, yields of Glc as a percentage of total Glc were lower for the forbs compared to corn stover. 24708722 4 19 theme herbaceous 647:656 arg1 component 609:617 a major component 601:617 a major component of such landscapes 601:636 However, a major component of such landscapes is often herbaceous dicotyledonous plants, also known as forbs. 24708722 4 19 theme herbaceous 647:656 arg1 plants 673:678 herbaceous dicotyledonous plants 647:678 herbaceous dicotyledonous plants 647:678 However, a major component of such landscapes is often herbaceous dicotyledonous plants, also known as forbs. 24708722 1 20 theme lignocellulosic 213:227 arg1 materials 229:237 lignocellulosic materials 213:237 lignocellulosic materials 213:237 BACKGROUND Many different feedstocks are under consideration for the practical production of biofuels from lignocellulosic materials. 24708722 13 21 theme Glc 2161:2163 arg1 yields 2165:2170 Glc yields 2161:2170 Glc yields 2161:2170 Addition of xyloglucanase and α-xylosidase, two enzymes targeting Glc-containing polysaccharides that are more abundant in dicotyledonous plants compared to grasses, enhanced Glc yields from lamb's quarters, but Glc yields were still lower than from corn stover. 24708722 8 22 theme northern 1242:1249 arg1 States 1302:1307 the continental United States 1279:1307 the continental United States 1279:1307 These plants are taxonomically diverse, widely distributed in northern temperate regions including the continental United States, and are weedy but not invasive. 24708722 8 22 theme northern 1242:1249 arg1 regions 1261:1267 northern temperate regions 1242:1267 northern temperate regions including the continental United States 1242:1307 These plants are taxonomically diverse, widely distributed in northern temperate regions including the continental United States, and are weedy but not invasive. 24708722 1 23 from materials 229:237 arg1 biofuels 199:206 biofuels 199:206 biofuels from lignocellulosic materials 199:237 BACKGROUND Many different feedstocks are under consideration for the practical production of biofuels from lignocellulosic materials. 24708722 1 23 from materials 229:237 arg1 production 185:194 the practical production 171:194 the practical production of biofuels from lignocellulosic materials 171:237 BACKGROUND Many different feedstocks are under consideration for the practical production of biofuels from lignocellulosic materials. 24708722 9 24 theme cell 1415:1418 arg1 walls 1420:1424 cell walls 1415:1424 cell walls 1415:1424 All of the forbs had lower total glucose (Glc) content from all sources (cell walls, sucrose, starch, glucosides, and free Glc) compared to corn stover (range 16.2 to 23.0% on a dry weight basis compared to 39.2% for corn stover). 24708722 11 25 theme significant 1800:1810 arg1 contributor 1812:1822 a significant contributor 1798:1822 a significant contributor to the lower yields 1798:1842 Enzyme inhibition by water-extractable compounds was not a significant contributor to the lower yields. 24708722 11 25 theme significant 1800:1810 arg1 inhibition 1748:1757 Enzyme inhibition 1741:1757 Enzyme inhibition by water-extractable compounds 1741:1788 Enzyme inhibition by water-extractable compounds was not a significant contributor to the lower yields. 24708722 1 26 theme different 122:130 arg1 feedstocks 132:141 BACKGROUND Many different feedstocks 106:141 BACKGROUND Many different feedstocks 106:141 BACKGROUND Many different feedstocks are under consideration for the practical production of biofuels from lignocellulosic materials. 24708722 10 27 theme Glc 1687:1689 arg1 percentage 1667:1676 a percentage 1665:1676 a percentage of total Glc 1665:1689 When digested with commercial enzyme mixtures after alkaline pretreatment, yields of Glc as a percentage of total Glc were lower for the forbs compared to corn stover. 24708722 8 28 theme United 1295:1300 arg1 States 1302:1307 the continental United States 1279:1307 the continental United States 1279:1307 These plants are taxonomically diverse, widely distributed in northern temperate regions including the continental United States, and are weedy but not invasive. 24708722 13 29 theme α-xylosidase 2016:2027 arg1 Addition 1986:1993 Addition 1986:1993 Addition of xyloglucanase and α-xylosidase, two enzymes targeting Glc-containing polysaccharides that are more abundant in dicotyledonous plants compared to grasses, 1986:2150 Addition of xyloglucanase and α-xylosidase, two enzymes targeting Glc-containing polysaccharides that are more abundant in dicotyledonous plants compared to grasses, enhanced Glc yields from lamb's quarters, but Glc yields were still lower than from corn stover. 24708722 11 30 theme lower 1831:1835 arg1 yields 1837:1842 the lower yields 1827:1842 the lower yields 1827:1842 Enzyme inhibition by water-extractable compounds was not a significant contributor to the lower yields. 24708722 12 31 theme enzyme 1920:1925 arg1 imbalance 1927:1935 enzyme imbalance 1920:1935 enzyme imbalance 1920:1935 Based on experiments with optimized cocktails of pure glycosyl hydrolases, enzyme imbalance probably accounted for much of the lower yields. 24708722 0 32 theme enzymatic 80:88 arg1 deconstruction 90:103 enzymatic deconstruction 80:103 enzymatic deconstruction 80:103 Factors contributing to the recalcitrance of herbaceous dicotyledons (forbs) to enzymatic deconstruction. 24708722 9 33 theme free 1460:1463 arg1 Glc 1465:1467 free Glc 1460:1467 free Glc 1460:1467 All of the forbs had lower total glucose (Glc) content from all sources (cell walls, sucrose, starch, glucosides, and free Glc) compared to corn stover (range 16.2 to 23.0% on a dry weight basis compared to 39.2% for corn stover). 24708722 3 34 theme biofuel 438:444 arg1 feedstocks 446:455 biofuel feedstocks 438:455 biofuel feedstocks 438:455 The use of old fields, restored prairie, or marginal lands to grow biofuel feedstocks offers several potential benefits including minimal agronomic inputs, reduced competition with food production, and high biodiversity. 24708722 3 35 theme restored 394:401 arg1 prairie 403:409 restored prairie 394:409 restored prairie 394:409 The use of old fields, restored prairie, or marginal lands to grow biofuel feedstocks offers several potential benefits including minimal agronomic inputs, reduced competition with food production, and high biodiversity. 24708722 13 36 from abundant 2097:2104 arg1 plants 2124:2129 dicotyledonous plants 2109:2129 dicotyledonous plants 2109:2129 Addition of xyloglucanase and α-xylosidase, two enzymes targeting Glc-containing polysaccharides that are more abundant in dicotyledonous plants compared to grasses, enhanced Glc yields from lamb's quarters, but Glc yields were still lower than from corn stover. 24708722 3 37 with biodiversity 578:589 arg1 production 557:566 food production 552:566 food production 552:566 The use of old fields, restored prairie, or marginal lands to grow biofuel feedstocks offers several potential benefits including minimal agronomic inputs, reduced competition with food production, and high biodiversity. 24708722 3 38 theme fields 386:391 arg1 use 375:377 The use 371:377 The use of old fields, restored prairie, or marginal lands to grow biofuel feedstocks 371:455 The use of old fields, restored prairie, or marginal lands to grow biofuel feedstocks offers several potential benefits including minimal agronomic inputs, reduced competition with food production, and high biodiversity. 24708722 2 39 theme particular 266:275 arg1 combination 277:287 any particular combination 262:287 any particular combination of economic, agronomic, and environmental conditions 262:340 The best choice under any particular combination of economic, agronomic, and environmental conditions depends on multiple factors. 24708722 3 40 theme potential 472:480 arg1 biodiversity 578:589 high biodiversity 573:589 high biodiversity 573:589 The use of old fields, restored prairie, or marginal lands to grow biofuel feedstocks offers several potential benefits including minimal agronomic inputs, reduced competition with food production, and high biodiversity. 24708722 3 40 theme potential 472:480 arg1 inputs 519:524 minimal agronomic inputs 501:524 minimal agronomic inputs 501:524 The use of old fields, restored prairie, or marginal lands to grow biofuel feedstocks offers several potential benefits including minimal agronomic inputs, reduced competition with food production, and high biodiversity. 24708722 3 40 theme potential 472:480 arg1 competition 535:545 reduced competition 527:545 reduced competition with food production 527:566 The use of old fields, restored prairie, or marginal lands to grow biofuel feedstocks offers several potential benefits including minimal agronomic inputs, reduced competition with food production, and high biodiversity. 24708722 3 40 theme potential 472:480 arg1 benefits 482:489 several potential benefits 464:489 several potential benefits including minimal agronomic inputs, reduced competition with food production, and high biodiversity 464:589 The use of old fields, restored prairie, or marginal lands to grow biofuel feedstocks offers several potential benefits including minimal agronomic inputs, reduced competition with food production, and high biodiversity. 24708722 7 41 theme Queen 1145:1149 arg1 lace 1158:1161 Queen Anne's lace 1145:1161 Queen Anne's lace (Daucus carota) 1145:1177 The forbs chosen for the study were lamb's quarters (Chenopodium album), goldenrod (Solidago canadensis), milkweed (Asclepias syriaca), and Queen Anne's lace (Daucus carota). 24708722 13 42 theme dicotyledonous 2109:2122 arg1 plants 2124:2129 dicotyledonous plants 2109:2129 dicotyledonous plants 2109:2129 Addition of xyloglucanase and α-xylosidase, two enzymes targeting Glc-containing polysaccharides that are more abundant in dicotyledonous plants compared to grasses, enhanced Glc yields from lamb's quarters, but Glc yields were still lower than from corn stover. 24708722 14 43 theme corn 2414:2417 arg1 stover 2419:2424 corn stover 2414:2424 corn stover 2414:2424 CONCLUSION The potential utilization of forb-rich plant communities as biofuel feedstocks must take into account their lower Glc content compared to grasses such as corn stover. 24708722 1 44 theme BACKGROUND 106:115 arg1 feedstocks 132:141 BACKGROUND Many different feedstocks 106:141 BACKGROUND Many different feedstocks 106:141 BACKGROUND Many different feedstocks are under consideration for the practical production of biofuels from lignocellulosic materials. 24708722 12 45 theme hydrolases 1908:1917 arg1 cocktails 1881:1889 optimized cocktails 1871:1889 optimized cocktails of pure glycosyl hydrolases 1871:1917 Based on experiments with optimized cocktails of pure glycosyl hydrolases, enzyme imbalance probably accounted for much of the lower yields. 24708722 3 46 theme marginal 415:422 arg1 lands 424:428 marginal lands 415:428 marginal lands 415:428 The use of old fields, restored prairie, or marginal lands to grow biofuel feedstocks offers several potential benefits including minimal agronomic inputs, reduced competition with food production, and high biodiversity. 24708722 6 47 dep RESULTS 858:864 arg1 studied 965:971 studied 965:971 were studied in comparison with corn stover 960:1002 RESULTS The factors that contribute to the yield of fermentable sugars from four representative forbs were studied in comparison with corn stover. 24708722 14 48 theme lower 2368:2372 arg1 content 2378:2384 their lower Glc content 2362:2384 their lower Glc content 2362:2384 CONCLUSION The potential utilization of forb-rich plant communities as biofuel feedstocks must take into account their lower Glc content compared to grasses such as corn stover. 24708722 11 49 theme water-extractable 1762:1778 arg1 compounds 1780:1788 water-extractable compounds 1762:1788 water-extractable compounds 1762:1788 Enzyme inhibition by water-extractable compounds was not a significant contributor to the lower yields. 24708722 9 50 theme Glc 1384:1386 arg1 content 1389:1395 lower total glucose (Glc) content 1363:1395 lower total glucose (Glc) content from all sources (cell walls, sucrose, starch, glucosides, and free Glc) 1363:1468 All of the forbs had lower total glucose (Glc) content from all sources (cell walls, sucrose, starch, glucosides, and free Glc) compared to corn stover (range 16.2 to 23.0% on a dry weight basis compared to 39.2% for corn stover). 24708722 5 51 theme considered 799:808 arg1 grasses 810:816 the more frequently considered grasses 779:816 the more frequently considered grasses 779:816 The potential and obstacles of using forbs as biofuel feedstocks compared to the more frequently considered grasses and woody plants are poorly understood. 24708722 9 52 theme range 1495:1499 arg1 % 1513:1513 range 16.2 to 23.0% 1495:1513 range 16.2 to 23.0% 1495:1513 All of the forbs had lower total glucose (Glc) content from all sources (cell walls, sucrose, starch, glucosides, and free Glc) compared to corn stover (range 16.2 to 23.0% on a dry weight basis compared to 39.2% for corn stover). 24708722 7 53 dep lace 1158:1161 arg1 carota 1171:1176 Daucus carota 1164:1176 Daucus carota 1164:1176 The forbs chosen for the study were lamb's quarters (Chenopodium album), goldenrod (Solidago canadensis), milkweed (Asclepias syriaca), and Queen Anne's lace (Daucus carota). 24708722 14 54 theme communities 2305:2315 arg1 utilization 2274:2284 The potential utilization 2260:2284 The potential utilization of forb-rich plant communities as biofuel feedstocks 2260:2337 CONCLUSION The potential utilization of forb-rich plant communities as biofuel feedstocks must take into account their lower Glc content compared to grasses such as corn stover. 24708722 3 55 theme agronomic 509:517 arg1 inputs 519:524 minimal agronomic inputs 501:524 minimal agronomic inputs 501:524 The use of old fields, restored prairie, or marginal lands to grow biofuel feedstocks offers several potential benefits including minimal agronomic inputs, reduced competition with food production, and high biodiversity. 24708722 0 56 theme herbaceous 45:54 arg1 forbs 70:74 forbs 70:74 forbs 70:74 Factors contributing to the recalcitrance of herbaceous dicotyledons (forbs) to enzymatic deconstruction. 24708722 0 56 theme herbaceous 45:54 arg1 dicotyledons 56:67 herbaceous dicotyledons 45:67 herbaceous dicotyledons (forbs) 45:75 Factors contributing to the recalcitrance of herbaceous dicotyledons (forbs) to enzymatic deconstruction. 24708722 10 57 theme corn 1728:1731 arg1 stover 1733:1738 corn stover 1728:1738 corn stover 1728:1738 When digested with commercial enzyme mixtures after alkaline pretreatment, yields of Glc as a percentage of total Glc were lower for the forbs compared to corn stover. 24708722 14 58 theme forb-rich 2289:2297 arg1 communities 2305:2315 forb-rich plant communities 2289:2315 forb-rich plant communities 2289:2315 CONCLUSION The potential utilization of forb-rich plant communities as biofuel feedstocks must take into account their lower Glc content compared to grasses such as corn stover. 24708722 2 59 theme multiple 353:360 arg1 factors 362:368 multiple factors 353:368 multiple factors 353:368 The best choice under any particular combination of economic, agronomic, and environmental conditions depends on multiple factors. 24708722 10 60 theme enzyme 1603:1608 arg1 mixtures 1610:1617 commercial enzyme mixtures 1592:1617 commercial enzyme mixtures 1592:1617 When digested with commercial enzyme mixtures after alkaline pretreatment, yields of Glc as a percentage of total Glc were lower for the forbs compared to corn stover. 24708722 9 61 dep stover 1487:1492 arg1 % 1513:1513 range 16.2 to 23.0% 1495:1513 range 16.2 to 23.0% 1495:1513 All of the forbs had lower total glucose (Glc) content from all sources (cell walls, sucrose, starch, glucosides, and free Glc) compared to corn stover (range 16.2 to 23.0% on a dry weight basis compared to 39.2% for corn stover). 24708722 10 62 theme commercial 1592:1601 arg1 mixtures 1610:1617 commercial enzyme mixtures 1592:1617 commercial enzyme mixtures 1592:1617 When digested with commercial enzyme mixtures after alkaline pretreatment, yields of Glc as a percentage of total Glc were lower for the forbs compared to corn stover. 24708722 15 63 theme enzyme 2444:2449 arg1 mixtures 2451:2458 new enzyme mixtures 2440:2458 new enzyme mixtures tailored to the different cell wall composition of forbs 2440:2515 Furthermore, new enzyme mixtures tailored to the different cell wall composition of forbs will have to be developed. 24708722 7 64 theme Asclepias 1121:1129 arg1 milkweed 1111:1118 milkweed 1111:1118 milkweed (Asclepias syriaca) 1111:1138 The forbs chosen for the study were lamb's quarters (Chenopodium album), goldenrod (Solidago canadensis), milkweed (Asclepias syriaca), and Queen Anne's lace (Daucus carota). 24708722 7 64 theme Asclepias 1121:1129 arg1 syriaca 1131:1137 Asclepias syriaca 1121:1137 Asclepias syriaca 1121:1137 The forbs chosen for the study were lamb's quarters (Chenopodium album), goldenrod (Solidago canadensis), milkweed (Asclepias syriaca), and Queen Anne's lace (Daucus carota). 24708722 6 65 theme representative 939:952 arg1 forbs 954:958 four representative forbs 934:958 four representative forbs 934:958 RESULTS The factors that contribute to the yield of fermentable sugars from four representative forbs were studied in comparison with corn stover. 24708722 4 66 theme landscapes 627:636 arg1 component 609:617 a major component 601:617 a major component of such landscapes 601:636 However, a major component of such landscapes is often herbaceous dicotyledonous plants, also known as forbs. 24708722 4 66 theme landscapes 627:636 arg1 plants 673:678 herbaceous dicotyledonous plants 647:678 herbaceous dicotyledonous plants 647:678 However, a major component of such landscapes is often herbaceous dicotyledonous plants, also known as forbs. 24708722 9 67 theme lower 1363:1367 arg1 content 1389:1395 lower total glucose (Glc) content 1363:1395 lower total glucose (Glc) content from all sources (cell walls, sucrose, starch, glucosides, and free Glc) 1363:1468 All of the forbs had lower total glucose (Glc) content from all sources (cell walls, sucrose, starch, glucosides, and free Glc) compared to corn stover (range 16.2 to 23.0% on a dry weight basis compared to 39.2% for corn stover). 24708722 9 68 theme weight 1524:1529 arg1 basis 1531:1535 a dry weight basis 1518:1535 a dry weight basis compared to 39.2% for corn stover 1518:1569 All of the forbs had lower total glucose (Glc) content from all sources (cell walls, sucrose, starch, glucosides, and free Glc) compared to corn stover (range 16.2 to 23.0% on a dry weight basis compared to 39.2% for corn stover). 24708722 3 69 with competition 535:545 arg1 production 557:566 food production 552:566 food production 552:566 The use of old fields, restored prairie, or marginal lands to grow biofuel feedstocks offers several potential benefits including minimal agronomic inputs, reduced competition with food production, and high biodiversity. 24708722 10 70 theme alkaline 1625:1632 arg1 pretreatment 1634:1645 alkaline pretreatment 1625:1645 alkaline pretreatment 1625:1645 When digested with commercial enzyme mixtures after alkaline pretreatment, yields of Glc as a percentage of total Glc were lower for the forbs compared to corn stover. 24708722 9 71 theme glucose 1375:1381 arg1 content 1389:1395 lower total glucose (Glc) content 1363:1395 lower total glucose (Glc) content from all sources (cell walls, sucrose, starch, glucosides, and free Glc) 1363:1468 All of the forbs had lower total glucose (Glc) content from all sources (cell walls, sucrose, starch, glucosides, and free Glc) compared to corn stover (range 16.2 to 23.0% on a dry weight basis compared to 39.2% for corn stover). 24708722 6 72 theme fermentable 910:920 arg1 sugars 922:927 fermentable sugars 910:927 fermentable sugars 910:927 RESULTS The factors that contribute to the yield of fermentable sugars from four representative forbs were studied in comparison with corn stover. 24708722 6 73 with comparison 976:985 arg1 stover 997:1002 corn stover 992:1002 corn stover 992:1002 RESULTS The factors that contribute to the yield of fermentable sugars from four representative forbs were studied in comparison with corn stover. 24708722 4 74 theme major 603:607 arg1 component 609:617 a major component 601:617 a major component of such landscapes 601:636 However, a major component of such landscapes is often herbaceous dicotyledonous plants, also known as forbs. 24708722 4 74 theme major 603:607 arg1 plants 673:678 herbaceous dicotyledonous plants 647:678 herbaceous dicotyledonous plants 647:678 However, a major component of such landscapes is often herbaceous dicotyledonous plants, also known as forbs. 24708722 7 75 theme Solidago 1089:1096 arg1 goldenrod 1078:1086 goldenrod 1078:1086 goldenrod (Solidago canadensis) 1078:1108 The forbs chosen for the study were lamb's quarters (Chenopodium album), goldenrod (Solidago canadensis), milkweed (Asclepias syriaca), and Queen Anne's lace (Daucus carota). 24708722 7 75 theme Solidago 1089:1096 arg1 canadensis 1098:1107 Solidago canadensis 1089:1107 Solidago canadensis 1089:1107 The forbs chosen for the study were lamb's quarters (Chenopodium album), goldenrod (Solidago canadensis), milkweed (Asclepias syriaca), and Queen Anne's lace (Daucus carota). 24708722 3 76 theme food 552:555 arg1 production 557:566 food production 552:566 food production 552:566 The use of old fields, restored prairie, or marginal lands to grow biofuel feedstocks offers several potential benefits including minimal agronomic inputs, reduced competition with food production, and high biodiversity. 24708722 15 77 theme forbs 2511:2515 arg1 composition 2496:2506 the different cell wall composition 2472:2506 the different cell wall composition of forbs 2472:2515 Furthermore, new enzyme mixtures tailored to the different cell wall composition of forbs will have to be developed. 24708722 1 78 theme practical 175:183 arg1 production 185:194 the practical production 171:194 the practical production of biofuels from lignocellulosic materials 171:237 BACKGROUND Many different feedstocks are under consideration for the practical production of biofuels from lignocellulosic materials. 24708722 2 79 theme environmental 317:329 arg1 conditions 331:340 economic, agronomic, and environmental conditions 292:340 economic, agronomic, and environmental conditions 292:340 The best choice under any particular combination of economic, agronomic, and environmental conditions depends on multiple factors. 24708722 15 80 theme cell 2486:2489 arg1 composition 2496:2506 the different cell wall composition 2472:2506 the different cell wall composition of forbs 2472:2515 Furthermore, new enzyme mixtures tailored to the different cell wall composition of forbs will have to be developed. 24708722 7 81 theme Chenopodium 1058:1068 arg1 quarters 1048:1055 lamb's quarters 1041:1055 lamb's quarters (Chenopodium album) 1041:1075 The forbs chosen for the study were lamb's quarters (Chenopodium album), goldenrod (Solidago canadensis), milkweed (Asclepias syriaca), and Queen Anne's lace (Daucus carota). 24708722 7 81 theme Chenopodium 1058:1068 arg1 album 1070:1074 Chenopodium album 1058:1074 Chenopodium album 1058:1074 The forbs chosen for the study were lamb's quarters (Chenopodium album), goldenrod (Solidago canadensis), milkweed (Asclepias syriaca), and Queen Anne's lace (Daucus carota). 24708722 9 82 dep % 1513:1513 arg1 to 1506:1507 to 1506:1507 to 1506:1507 All of the forbs had lower total glucose (Glc) content from all sources (cell walls, sucrose, starch, glucosides, and free Glc) compared to corn stover (range 16.2 to 23.0% on a dry weight basis compared to 39.2% for corn stover). 24708722 2 83 theme best 244:247 arg1 choice 249:254 The best choice 240:254 The best choice under any particular combination of economic, agronomic, and environmental conditions 240:340 The best choice under any particular combination of economic, agronomic, and environmental conditions depends on multiple factors. 24708722 1 84 theme Many 117:120 arg1 feedstocks 132:141 BACKGROUND Many different feedstocks 106:141 BACKGROUND Many different feedstocks 106:141 BACKGROUND Many different feedstocks are under consideration for the practical production of biofuels from lignocellulosic materials. 24708722 8 85 theme temperate 1251:1259 arg1 States 1302:1307 the continental United States 1279:1307 the continental United States 1279:1307 These plants are taxonomically diverse, widely distributed in northern temperate regions including the continental United States, and are weedy but not invasive. 24708722 8 85 theme temperate 1251:1259 arg1 regions 1261:1267 northern temperate regions 1242:1267 northern temperate regions including the continental United States 1242:1307 These plants are taxonomically diverse, widely distributed in northern temperate regions including the continental United States, and are weedy but not invasive. 24708722 12 86 with experiments 1854:1864 arg1 cocktails 1881:1889 optimized cocktails 1871:1889 optimized cocktails of pure glycosyl hydrolases 1871:1917 Based on experiments with optimized cocktails of pure glycosyl hydrolases, enzyme imbalance probably accounted for much of the lower yields. 24708722 3 87 theme high 573:576 arg1 biodiversity 578:589 high biodiversity 573:589 high biodiversity 573:589 The use of old fields, restored prairie, or marginal lands to grow biofuel feedstocks offers several potential benefits including minimal agronomic inputs, reduced competition with food production, and high biodiversity. 24708722 10 88 theme total 1681:1685 arg1 Glc 1687:1689 total Glc 1681:1689 total Glc 1681:1689 When digested with commercial enzyme mixtures after alkaline pretreatment, yields of Glc as a percentage of total Glc were lower for the forbs compared to corn stover. 24708722 8 89 theme continental 1283:1293 arg1 States 1302:1307 the continental United States 1279:1307 the continental United States 1279:1307 These plants are taxonomically diverse, widely distributed in northern temperate regions including the continental United States, and are weedy but not invasive. 24708722 3 90 theme old 382:384 arg1 fields 386:391 old fields 382:391 old fields 382:391 The use of old fields, restored prairie, or marginal lands to grow biofuel feedstocks offers several potential benefits including minimal agronomic inputs, reduced competition with food production, and high biodiversity. 24708722 1 91 from production 185:194 arg1 materials 229:237 lignocellulosic materials 213:237 lignocellulosic materials 213:237 BACKGROUND Many different feedstocks are under consideration for the practical production of biofuels from lignocellulosic materials. 24708722 5 92 dep potential 706:714 arg1 The 702:704 The 702:704 The 702:704 The potential and obstacles of using forbs as biofuel feedstocks compared to the more frequently considered grasses and woody plants are poorly understood. 24708722 13 93 from plants 2124:2129 arg1 abundant 2097:2104 abundant 2097:2104 abundant 2097:2104 Addition of xyloglucanase and α-xylosidase, two enzymes targeting Glc-containing polysaccharides that are more abundant in dicotyledonous plants compared to grasses, enhanced Glc yields from lamb's quarters, but Glc yields were still lower than from corn stover. 24708722 5 94 theme woody 822:826 arg1 plants 828:833 woody plants 822:833 woody plants 822:833 The potential and obstacles of using forbs as biofuel feedstocks compared to the more frequently considered grasses and woody plants are poorly understood. 24708722 9 95 from % 1513:1513 arg1 basis 1531:1535 a dry weight basis 1518:1535 a dry weight basis compared to 39.2% for corn stover 1518:1569 All of the forbs had lower total glucose (Glc) content from all sources (cell walls, sucrose, starch, glucosides, and free Glc) compared to corn stover (range 16.2 to 23.0% on a dry weight basis compared to 39.2% for corn stover). 24708722 3 96 theme prairie 403:409 arg1 use 375:377 The use 371:377 The use of old fields, restored prairie, or marginal lands to grow biofuel feedstocks 371:455 The use of old fields, restored prairie, or marginal lands to grow biofuel feedstocks offers several potential benefits including minimal agronomic inputs, reduced competition with food production, and high biodiversity. 24708722 14 97 theme Glc 2374:2376 arg1 content 2378:2384 their lower Glc content 2362:2384 their lower Glc content 2362:2384 CONCLUSION The potential utilization of forb-rich plant communities as biofuel feedstocks must take into account their lower Glc content compared to grasses such as corn stover. 24708722 14 98 dep CONCLUSION 2249:2258 arg1 take 2344:2347 take 2344:2347 must take into account their lower Glc content compared to grasses such as corn stover 2339:2424 CONCLUSION The potential utilization of forb-rich plant communities as biofuel feedstocks must take into account their lower Glc content compared to grasses such as corn stover. 24708722 11 99 theme Enzyme 1741:1746 arg1 inhibition 1748:1757 Enzyme inhibition 1741:1757 Enzyme inhibition by water-extractable compounds 1741:1788 Enzyme inhibition by water-extractable compounds was not a significant contributor to the lower yields. 24708722 11 99 theme Enzyme 1741:1746 arg1 contributor 1812:1822 a significant contributor 1798:1822 a significant contributor to the lower yields 1798:1842 Enzyme inhibition by water-extractable compounds was not a significant contributor to the lower yields. 24708722 9 100 theme corn 1482:1485 arg1 stover 1487:1492 corn stover 1482:1492 corn stover (range 16.2 to 23.0% on a dry weight basis compared to 39.2% for corn stover) 1482:1570 All of the forbs had lower total glucose (Glc) content from all sources (cell walls, sucrose, starch, glucosides, and free Glc) compared to corn stover (range 16.2 to 23.0% on a dry weight basis compared to 39.2% for corn stover). 24708722 12 101 theme glycosyl 1899:1906 arg1 hydrolases 1908:1917 pure glycosyl hydrolases 1894:1917 pure glycosyl hydrolases 1894:1917 Based on experiments with optimized cocktails of pure glycosyl hydrolases, enzyme imbalance probably accounted for much of the lower yields. 24708722 12 102 theme lower 1972:1976 arg1 yields 1978:1983 the lower yields 1968:1983 the lower yields 1968:1983 Based on experiments with optimized cocktails of pure glycosyl hydrolases, enzyme imbalance probably accounted for much of the lower yields. 24708722 13 103 theme corn 2236:2239 arg1 stover 2241:2246 corn stover 2236:2246 corn stover 2236:2246 Addition of xyloglucanase and α-xylosidase, two enzymes targeting Glc-containing polysaccharides that are more abundant in dicotyledonous plants compared to grasses, enhanced Glc yields from lamb's quarters, but Glc yields were still lower than from corn stover. 24708722 3 104 theme lands 424:428 arg1 use 375:377 The use 371:377 The use of old fields, restored prairie, or marginal lands to grow biofuel feedstocks 371:455 The use of old fields, restored prairie, or marginal lands to grow biofuel feedstocks offers several potential benefits including minimal agronomic inputs, reduced competition with food production, and high biodiversity. 24708722 3 105 theme several 464:470 arg1 biodiversity 578:589 high biodiversity 573:589 high biodiversity 573:589 The use of old fields, restored prairie, or marginal lands to grow biofuel feedstocks offers several potential benefits including minimal agronomic inputs, reduced competition with food production, and high biodiversity. 24708722 3 105 theme several 464:470 arg1 inputs 519:524 minimal agronomic inputs 501:524 minimal agronomic inputs 501:524 The use of old fields, restored prairie, or marginal lands to grow biofuel feedstocks offers several potential benefits including minimal agronomic inputs, reduced competition with food production, and high biodiversity. 24708722 3 105 theme several 464:470 arg1 competition 535:545 reduced competition 527:545 reduced competition with food production 527:566 The use of old fields, restored prairie, or marginal lands to grow biofuel feedstocks offers several potential benefits including minimal agronomic inputs, reduced competition with food production, and high biodiversity. 24708722 3 105 theme several 464:470 arg1 benefits 482:489 several potential benefits 464:489 several potential benefits including minimal agronomic inputs, reduced competition with food production, and high biodiversity 464:589 The use of old fields, restored prairie, or marginal lands to grow biofuel feedstocks offers several potential benefits including minimal agronomic inputs, reduced competition with food production, and high biodiversity. 24708722 0 106 theme dicotyledons 56:67 arg1 recalcitrance 28:40 the recalcitrance 24:40 the recalcitrance of herbaceous dicotyledons (forbs) to enzymatic deconstruction 24:103 Factors contributing to the recalcitrance of herbaceous dicotyledons (forbs) to enzymatic deconstruction. 24708722 12 107 theme optimized 1871:1879 arg1 cocktails 1881:1889 optimized cocktails 1871:1889 optimized cocktails of pure glycosyl hydrolases 1871:1917 Based on experiments with optimized cocktails of pure glycosyl hydrolases, enzyme imbalance probably accounted for much of the lower yields. 24708722 6 108 from forbs 954:958 arg1 yield 901:905 the yield 897:905 the yield of fermentable sugars from four representative forbs 897:958 RESULTS The factors that contribute to the yield of fermentable sugars from four representative forbs were studied in comparison with corn stover. 24708722 14 109 theme plant 2299:2303 arg1 communities 2305:2315 forb-rich plant communities 2289:2315 forb-rich plant communities 2289:2315 CONCLUSION The potential utilization of forb-rich plant communities as biofuel feedstocks must take into account their lower Glc content compared to grasses such as corn stover. 24708722 9 110 from sources 1406:1412 arg1 content 1389:1395 lower total glucose (Glc) content 1363:1395 lower total glucose (Glc) content from all sources (cell walls, sucrose, starch, glucosides, and free Glc) 1363:1468 All of the forbs had lower total glucose (Glc) content from all sources (cell walls, sucrose, starch, glucosides, and free Glc) compared to corn stover (range 16.2 to 23.0% on a dry weight basis compared to 39.2% for corn stover). 24708722 4 111 theme such 622:625 arg1 landscapes 627:636 such landscapes 622:636 such landscapes 622:636 However, a major component of such landscapes is often herbaceous dicotyledonous plants, also known as forbs. 24708722 3 112 theme minimal 501:507 arg1 inputs 519:524 minimal agronomic inputs 501:524 minimal agronomic inputs 501:524 The use of old fields, restored prairie, or marginal lands to grow biofuel feedstocks offers several potential benefits including minimal agronomic inputs, reduced competition with food production, and high biodiversity. 24708722 15 113 theme new 2440:2442 arg1 mixtures 2451:2458 new enzyme mixtures 2440:2458 new enzyme mixtures tailored to the different cell wall composition of forbs 2440:2515 Furthermore, new enzyme mixtures tailored to the different cell wall composition of forbs will have to be developed. 24708722 4 114 theme dicotyledonous 658:671 arg1 component 609:617 a major component 601:617 a major component of such landscapes 601:636 However, a major component of such landscapes is often herbaceous dicotyledonous plants, also known as forbs. 24708722 4 114 theme dicotyledonous 658:671 arg1 plants 673:678 herbaceous dicotyledonous plants 647:678 herbaceous dicotyledonous plants 647:678 However, a major component of such landscapes is often herbaceous dicotyledonous plants, also known as forbs. 24708722 9 115 dep sources 1406:1412 arg1 sucrose 1427:1433 sucrose 1427:1433 sucrose 1427:1433 All of the forbs had lower total glucose (Glc) content from all sources (cell walls, sucrose, starch, glucosides, and free Glc) compared to corn stover (range 16.2 to 23.0% on a dry weight basis compared to 39.2% for corn stover). 24708722 9 115 dep sources 1406:1412 arg1 Glc 1465:1467 free Glc 1460:1467 free Glc 1460:1467 All of the forbs had lower total glucose (Glc) content from all sources (cell walls, sucrose, starch, glucosides, and free Glc) compared to corn stover (range 16.2 to 23.0% on a dry weight basis compared to 39.2% for corn stover). 24708722 9 115 dep sources 1406:1412 arg1 walls 1420:1424 cell walls 1415:1424 cell walls 1415:1424 All of the forbs had lower total glucose (Glc) content from all sources (cell walls, sucrose, starch, glucosides, and free Glc) compared to corn stover (range 16.2 to 23.0% on a dry weight basis compared to 39.2% for corn stover). 24708722 9 115 dep sources 1406:1412 arg1 glucosides 1444:1453 glucosides 1444:1453 glucosides 1444:1453 All of the forbs had lower total glucose (Glc) content from all sources (cell walls, sucrose, starch, glucosides, and free Glc) compared to corn stover (range 16.2 to 23.0% on a dry weight basis compared to 39.2% for corn stover). 24708722 9 115 dep sources 1406:1412 arg1 starch 1436:1441 starch 1436:1441 starch 1436:1441 All of the forbs had lower total glucose (Glc) content from all sources (cell walls, sucrose, starch, glucosides, and free Glc) compared to corn stover (range 16.2 to 23.0% on a dry weight basis compared to 39.2% for corn stover). 24708722 14 116 theme potential 2264:2272 arg1 utilization 2274:2284 The potential utilization 2260:2284 The potential utilization of forb-rich plant communities as biofuel feedstocks 2260:2337 CONCLUSION The potential utilization of forb-rich plant communities as biofuel feedstocks must take into account their lower Glc content compared to grasses such as corn stover. 24708722 13 117 theme Glc-containing 2052:2065 arg1 polysaccharides 2067:2081 Glc-containing polysaccharides 2052:2081 Glc-containing polysaccharides that are more abundant in dicotyledonous plants compared to grasses 2052:2149 Addition of xyloglucanase and α-xylosidase, two enzymes targeting Glc-containing polysaccharides that are more abundant in dicotyledonous plants compared to grasses, enhanced Glc yields from lamb's quarters, but Glc yields were still lower than from corn stover. 29312209 4 0 theme microbiome 571:580 arg1 intervention 547:558 the intervention 543:558 the intervention of the gut microbiome 543:580 Understanding the forces that guide microbiome development and composition is important to determine its role in health and in the intervention of the gut microbiome as a therapeutic tool. 29312209 16 1 theme metabolic 2211:2219 arg1 resources 2221:2229 metabolic resources 2211:2229 metabolic resources 2211:2229 The model could be scaled to include data from larger consortia, or be applied to microbial communities where sharing metabolic resources is important in shaping bacterial abundance. 29312209 5 2 theme genome-scale 643:654 arg1 models 656:661 genome-scale models 643:661 genome-scale models 643:661 Recently, modeling approaches such as genome-scale models and time-series analyses have been useful to predict microbial interactions. 29312209 10 3 theme good 1393:1396 arg1 correlation 1398:1408 a good correlation 1391:1408 a good correlation 1391:1408 In addition, a good correlation was observed between the experimental data with predicted FOS consumption and acid production. 29312209 17 4 with consortia 2335:2343 arg1 production 2389:2398 higher acid production 2377:2398 higher acid production 2377:2398 Moreover, the model could be useful in designing microbial consortia with desired properties such as higher acid production. 29312209 17 4 with consortia 2335:2343 arg1 properties 2358:2367 desired properties 2350:2367 desired properties such as higher acid production 2350:2398 Moreover, the model could be useful in designing microbial consortia with desired properties such as higher acid production. 29312209 1 5 contain has 135:137 arg2 influence 153:161 a significant influence 139:161 a significant influence 139:161 The gut microbiome is a complex microbial community that has a significant influence on the host. 29312209 1 5 contain has 135:137 arg1 community 120:128 a complex microbial community 100:128 a complex microbial community that has a significant influence on the host 100:173 The gut microbiome is a complex microbial community that has a significant influence on the host. 29312209 1 5 contain has 135:137 arg1 microbiome 86:95 The gut microbiome 78:95 The gut microbiome 78:95 The gut microbiome is a complex microbial community that has a significant influence on the host. 29312209 5 6 theme modeling 615:622 arg1 approaches 624:633 modeling approaches 615:633 modeling approaches such as genome-scale models and time-series analyses 615:686 Recently, modeling approaches such as genome-scale models and time-series analyses have been useful to predict microbial interactions. 29312209 5 6 theme modeling 615:622 arg1 models 656:661 genome-scale models 643:661 genome-scale models 643:661 Recently, modeling approaches such as genome-scale models and time-series analyses have been useful to predict microbial interactions. 29312209 5 6 theme modeling 615:622 arg1 analyses 679:686 time-series analyses 667:686 time-series analyses 667:686 Recently, modeling approaches such as genome-scale models and time-series analyses have been useful to predict microbial interactions. 29312209 10 7 theme experimental 1435:1446 arg1 data 1448:1451 the experimental data 1431:1451 the experimental data with predicted FOS consumption and acid production 1431:1502 In addition, a good correlation was observed between the experimental data with predicted FOS consumption and acid production. 29312209 9 8 from abundance 1329:1337 arg1 co-cultures 1342:1352 co-cultures 1342:1352 co-cultures from mono-culture data 1342:1375 After parameter optimization, the model accurately predicted bacterial abundance in co-cultures from mono-culture data. 29312209 9 8 from abundance 1329:1337 arg1 data 1372:1375 mono-culture data 1359:1375 mono-culture data 1359:1375 After parameter optimization, the model accurately predicted bacterial abundance in co-cultures from mono-culture data. 29312209 13 9 theme acetate 1772:1778 arg1 depletion 1759:1767 depletion 1759:1767 depletion of acetate and lactate 1759:1790 The model was able to predict the predominance of the two aforementioned species, as well as depletion of acetate and lactate. 29312209 13 10 theme lactate 1784:1790 arg1 depletion 1759:1767 depletion 1759:1767 depletion of acetate and lactate 1759:1790 The model was able to predict the predominance of the two aforementioned species, as well as depletion of acetate and lactate. 29312209 3 11 from carbohydrates 334:346 arg1 products 313:320 breakdown products 303:320 breakdown products from larger carbohydrates and short chain fatty acids 303:374 In this environment, breakdown products from larger carbohydrates and short chain fatty acids are commonly shared among gut microbes. 29312209 8 12 theme metabolic 1216:1224 arg1 lactate 1248:1254 lactate 1248:1254 lactate 1248:1254 infantis, Lactobacillus acidophilus, Escherichia coli, and Bacteroides vulgatus), one substrate (fructooligosaccharides, FOS), and evaluating two metabolic products (acetate and lactate). 29312209 8 12 theme metabolic 1216:1224 arg1 acetate 1236:1242 acetate 1236:1242 acetate 1236:1242 infantis, Lactobacillus acidophilus, Escherichia coli, and Bacteroides vulgatus), one substrate (fructooligosaccharides, FOS), and evaluating two metabolic products (acetate and lactate). 29312209 8 12 theme metabolic 1216:1224 arg1 products 1226:1233 two metabolic products 1212:1233 two metabolic products (acetate and lactate) 1212:1255 infantis, Lactobacillus acidophilus, Escherichia coli, and Bacteroides vulgatus), one substrate (fructooligosaccharides, FOS), and evaluating two metabolic products (acetate and lactate). 29312209 15 13 theme microbial 1911:1919 arg1 abundance 1921:1929 microbial abundance 1911:1929 microbial abundance 1911:1929 These results suggest that variations in microbial abundance and activities in the infant gut were mainly explained by metabolic interactions, and could be properly modeled using Monod kinetics with metabolic interactions. 29312209 5 14 theme microbial 716:724 arg1 interactions 726:737 microbial interactions 716:737 microbial interactions 716:737 Recently, modeling approaches such as genome-scale models and time-series analyses have been useful to predict microbial interactions. 29312209 7 15 theme gut 1024:1026 arg1 microbiome 1028:1037 the infant gut microbiome 1013:1037 the infant gut microbiome 1013:1037 The model was developed using experimental in vitro data from a system comprising four microorganisms of the infant gut microbiome (Bifidobacterium longum subsp. 29312209 4 16 theme microbiome 452:461 arg1 development 463:473 microbiome development 452:473 microbiome development 452:473 Understanding the forces that guide microbiome development and composition is important to determine its role in health and in the intervention of the gut microbiome as a therapeutic tool. 29312209 16 17 theme microbial 2175:2183 arg1 communities 2185:2195 microbial communities 2175:2195 microbial communities 2175:2195 The model could be scaled to include data from larger consortia, or be applied to microbial communities where sharing metabolic resources is important in shaping bacterial abundance. 29312209 1 18 theme complex 102:108 arg1 community 120:128 a complex microbial community 100:128 a complex microbial community that has a significant influence on the host 100:173 The gut microbiome is a complex microbial community that has a significant influence on the host. 29312209 1 18 theme complex 102:108 arg1 microbiome 86:95 The gut microbiome 78:95 The gut microbiome 78:95 The gut microbiome is a complex microbial community that has a significant influence on the host. 29312209 9 19 theme parameter 1264:1272 arg1 optimization 1274:1285 parameter optimization 1264:1285 parameter optimization 1264:1285 After parameter optimization, the model accurately predicted bacterial abundance in co-cultures from mono-culture data. 29312209 12 20 theme Further 1574:1580 arg1 validation 1588:1597 Further model validation 1574:1597 Further model validation 1574:1597 Further model validation included cultures with the four-species in a bioreactor using FOS. 29312209 17 21 theme desired 2350:2356 arg1 production 2389:2398 higher acid production 2377:2398 higher acid production 2377:2398 Moreover, the model could be useful in designing microbial consortia with desired properties such as higher acid production. 29312209 17 21 theme desired 2350:2356 arg1 properties 2358:2367 desired properties 2350:2367 desired properties such as higher acid production 2350:2398 Moreover, the model could be useful in designing microbial consortia with desired properties such as higher acid production. 29312209 0 22 theme Infant 55:60 arg1 Microbiome 66:75 the Infant Gut Microbiome 51:75 the Infant Gut Microbiome 51:75 Modeling Metabolic Interactions in a Consortium of the Infant Gut Microbiome. 29312209 3 23 theme breakdown 303:311 arg1 products 313:320 breakdown products 303:320 breakdown products from larger carbohydrates and short chain fatty acids 303:374 In this environment, breakdown products from larger carbohydrates and short chain fatty acids are commonly shared among gut microbes. 29312209 10 24 theme FOS 1468:1470 arg1 consumption 1472:1482 predicted FOS consumption 1458:1482 predicted FOS consumption 1458:1482 In addition, a good correlation was observed between the experimental data with predicted FOS consumption and acid production. 29312209 0 25 theme Microbiome 66:75 arg1 Consortium 37:46 a Consortium 35:46 a Consortium of the Infant Gut Microbiome 35:75 Modeling Metabolic Interactions in a Consortium of the Infant Gut Microbiome. 29312209 16 26 from important 2234:2242 arg1 abundance 2265:2273 shaping bacterial abundance 2247:2273 shaping bacterial abundance 2247:2273 The model could be scaled to include data from larger consortia, or be applied to microbial communities where sharing metabolic resources is important in shaping bacterial abundance. 29312209 1 27 theme significant 141:151 arg1 influence 153:161 a significant influence 139:161 a significant influence 139:161 The gut microbiome is a complex microbial community that has a significant influence on the host. 29312209 3 28 theme short 352:356 arg1 acids 370:374 short chain fatty acids 352:374 short chain fatty acids 352:374 In this environment, breakdown products from larger carbohydrates and short chain fatty acids are commonly shared among gut microbes. 29312209 13 29 theme species 1739:1745 arg1 predominance 1700:1711 the predominance 1696:1711 the predominance of the two aforementioned species 1696:1745 The model was able to predict the predominance of the two aforementioned species, as well as depletion of acetate and lactate. 29312209 8 30 dep substrate 1156:1164 arg1 fructooligosaccharides 1167:1188 fructooligosaccharides 1167:1188 fructooligosaccharides 1167:1188 infantis, Lactobacillus acidophilus, Escherichia coli, and Bacteroides vulgatus), one substrate (fructooligosaccharides, FOS), and evaluating two metabolic products (acetate and lactate). 29312209 8 30 dep substrate 1156:1164 arg1 FOS 1191:1193 FOS 1191:1193 FOS 1191:1193 infantis, Lactobacillus acidophilus, Escherichia coli, and Bacteroides vulgatus), one substrate (fructooligosaccharides, FOS), and evaluating two metabolic products (acetate and lactate). 29312209 16 31 theme bacterial 2255:2263 arg1 abundance 2265:2273 shaping bacterial abundance 2247:2273 shaping bacterial abundance 2247:2273 The model could be scaled to include data from larger consortia, or be applied to microbial communities where sharing metabolic resources is important in shaping bacterial abundance. 29312209 9 32 from data 1372:1375 arg1 co-cultures 1342:1352 co-cultures 1342:1352 co-cultures from mono-culture data 1342:1375 After parameter optimization, the model accurately predicted bacterial abundance in co-cultures from mono-culture data. 29312209 9 32 from data 1372:1375 arg1 abundance 1329:1337 bacterial abundance 1319:1337 bacterial abundance in co-cultures from mono-culture data 1319:1375 After parameter optimization, the model accurately predicted bacterial abundance in co-cultures from mono-culture data. 29312209 7 33 theme in 951:952 arg1 data 960:963 experimental in vitro data 938:963 experimental in vitro data from a system comprising four microorganisms of the infant gut microbiome (Bifidobacterium longum subsp 938:1067 The model was developed using experimental in vitro data from a system comprising four microorganisms of the infant gut microbiome (Bifidobacterium longum subsp. 29312209 16 34 theme shaping 2247:2253 arg1 abundance 2265:2273 shaping bacterial abundance 2247:2273 shaping bacterial abundance 2247:2273 The model could be scaled to include data from larger consortia, or be applied to microbial communities where sharing metabolic resources is important in shaping bacterial abundance. 29312209 16 35 theme larger 2140:2145 arg1 consortia 2147:2155 larger consortia 2140:2155 larger consortia 2140:2155 The model could be scaled to include data from larger consortia, or be applied to microbial communities where sharing metabolic resources is important in shaping bacterial abundance. 29312209 0 36 theme Modeling 0:7 arg1 Interactions 19:30 Modeling Metabolic Interactions 0:30 Modeling Metabolic Interactions 0:30 Modeling Metabolic Interactions in a Consortium of the Infant Gut Microbiome. 29312209 1 37 theme gut 82:84 arg1 community 120:128 a complex microbial community 100:128 a complex microbial community that has a significant influence on the host 100:173 The gut microbiome is a complex microbial community that has a significant influence on the host. 29312209 1 37 theme gut 82:84 arg1 microbiome 86:95 The gut microbiome 78:95 The gut microbiome 78:95 The gut microbiome is a complex microbial community that has a significant influence on the host. 29312209 3 38 theme fatty 364:368 arg1 acids 370:374 short chain fatty acids 352:374 short chain fatty acids 352:374 In this environment, breakdown products from larger carbohydrates and short chain fatty acids are commonly shared among gut microbes. 29312209 17 39 theme acid 2384:2387 arg1 production 2389:2398 higher acid production 2377:2398 higher acid production 2377:2398 Moreover, the model could be useful in designing microbial consortia with desired properties such as higher acid production. 29312209 9 40 theme mono-culture 1359:1370 arg1 data 1372:1375 mono-culture data 1359:1375 mono-culture data 1359:1375 After parameter optimization, the model accurately predicted bacterial abundance in co-cultures from mono-culture data. 29312209 3 41 theme gut 402:404 arg1 microbes 406:413 gut microbes 402:413 gut microbes 402:413 In this environment, breakdown products from larger carbohydrates and short chain fatty acids are commonly shared among gut microbes. 29312209 15 42 from activities 1935:1944 arg1 gut 1960:1962 the infant gut 1949:1962 the infant gut 1949:1962 These results suggest that variations in microbial abundance and activities in the infant gut were mainly explained by metabolic interactions, and could be properly modeled using Monod kinetics with metabolic interactions. 29312209 15 42 from activities 1935:1944 arg1 abundance 1921:1929 microbial abundance 1911:1929 microbial abundance 1911:1929 These results suggest that variations in microbial abundance and activities in the infant gut were mainly explained by metabolic interactions, and could be properly modeled using Monod kinetics with metabolic interactions. 29312209 6 43 theme growth 840:845 arg1 equations 847:855 microbial growth equations 830:855 microbial growth equations that incorporate metabolic sharing and inhibition 830:905 In this study, a bottom-up approach was followed to develop a mathematical model based on microbial growth equations that incorporate metabolic sharing and inhibition. 29312209 0 44 dep Interactions 19:30 arg1 Consortium 37:46 a Consortium 35:46 a Consortium of the Infant Gut Microbiome 35:75 Modeling Metabolic Interactions in a Consortium of the Infant Gut Microbiome. 29312209 4 45 theme therapeutic 587:597 arg1 tool 599:602 a therapeutic tool 585:602 a therapeutic tool 585:602 Understanding the forces that guide microbiome development and composition is important to determine its role in health and in the intervention of the gut microbiome as a therapeutic tool. 29312209 17 46 theme higher 2377:2382 arg1 production 2389:2398 higher acid production 2377:2398 higher acid production 2377:2398 Moreover, the model could be useful in designing microbial consortia with desired properties such as higher acid production. 29312209 8 47 dep infantis 1070:1077 arg1 acidophilus 1094:1104 Lactobacillus acidophilus 1080:1104 Lactobacillus acidophilus 1080:1104 infantis, Lactobacillus acidophilus, Escherichia coli, and Bacteroides vulgatus), one substrate (fructooligosaccharides, FOS), and evaluating two metabolic products (acetate and lactate). 29312209 8 47 dep infantis 1070:1077 arg1 coli 1119:1122 Escherichia coli 1107:1122 Escherichia coli 1107:1122 infantis, Lactobacillus acidophilus, Escherichia coli, and Bacteroides vulgatus), one substrate (fructooligosaccharides, FOS), and evaluating two metabolic products (acetate and lactate). 29312209 8 47 dep infantis 1070:1077 arg1 vulgatus 1141:1148 Bacteroides vulgatus 1129:1148 Bacteroides vulgatus 1129:1148 infantis, Lactobacillus acidophilus, Escherichia coli, and Bacteroides vulgatus), one substrate (fructooligosaccharides, FOS), and evaluating two metabolic products (acetate and lactate). 29312209 15 48 from variations 1897:1906 arg1 gut 1960:1962 the infant gut 1949:1962 the infant gut 1949:1962 These results suggest that variations in microbial abundance and activities in the infant gut were mainly explained by metabolic interactions, and could be properly modeled using Monod kinetics with metabolic interactions. 29312209 15 48 from variations 1897:1906 arg1 abundance 1921:1929 microbial abundance 1911:1929 microbial abundance 1911:1929 These results suggest that variations in microbial abundance and activities in the infant gut were mainly explained by metabolic interactions, and could be properly modeled using Monod kinetics with metabolic interactions. 29312209 4 49 from role 521:524 arg1 intervention 547:558 the intervention 543:558 the intervention of the gut microbiome 543:580 Understanding the forces that guide microbiome development and composition is important to determine its role in health and in the intervention of the gut microbiome as a therapeutic tool. 29312209 4 49 from role 521:524 arg1 health 529:534 health 529:534 health 529:534 Understanding the forces that guide microbiome development and composition is important to determine its role in health and in the intervention of the gut microbiome as a therapeutic tool. 29312209 4 50 theme gut 567:569 arg1 microbiome 571:580 the gut microbiome 563:580 the gut microbiome 563:580 Understanding the forces that guide microbiome development and composition is important to determine its role in health and in the intervention of the gut microbiome as a therapeutic tool. 29312209 6 51 theme mathematical 802:813 arg1 model 815:819 a mathematical model 800:819 a mathematical model based on microbial growth equations that incorporate metabolic sharing and inhibition 800:905 In this study, a bottom-up approach was followed to develop a mathematical model based on microbial growth equations that incorporate metabolic sharing and inhibition. 29312209 15 52 theme metabolic 2069:2077 arg1 interactions 2079:2090 metabolic interactions 2069:2090 metabolic interactions 2069:2090 These results suggest that variations in microbial abundance and activities in the infant gut were mainly explained by metabolic interactions, and could be properly modeled using Monod kinetics with metabolic interactions. 29312209 7 53 dep longum 1056:1061 arg1 subsp 1063:1067 subsp 1063:1067 four microorganisms of the infant gut microbiome (Bifidobacterium longum subsp 990:1067 The model was developed using experimental in vitro data from a system comprising four microorganisms of the infant gut microbiome (Bifidobacterium longum subsp. 29312209 2 54 theme complex 257:263 arg1 polysaccharides 265:279 complex polysaccharides 257:279 complex polysaccharides 257:279 Microbial interactions in the gut are mediated by dietary substrates, especially complex polysaccharides. 29312209 2 54 theme complex 257:263 arg1 substrates 234:243 dietary substrates 226:243 dietary substrates 226:243 Microbial interactions in the gut are mediated by dietary substrates, especially complex polysaccharides. 29312209 2 55 from interactions 186:197 arg1 gut 206:208 the gut 202:208 the gut 202:208 Microbial interactions in the gut are mediated by dietary substrates, especially complex polysaccharides. 29312209 12 56 with cultures 1608:1615 arg1 four-species 1626:1637 the four-species 1622:1637 the four-species in a bioreactor using FOS 1622:1663 Further model validation included cultures with the four-species in a bioreactor using FOS. 29312209 15 57 theme metabolic 1989:1997 arg1 interactions 1999:2010 metabolic interactions 1989:2010 metabolic interactions 1989:2010 These results suggest that variations in microbial abundance and activities in the infant gut were mainly explained by metabolic interactions, and could be properly modeled using Monod kinetics with metabolic interactions. 29312209 14 58 theme parameter 1827:1835 arg1 identifiability 1837:1851 parameter identifiability 1827:1851 parameter identifiability 1827:1851 Finally, the model was tested for parameter identifiability and sensitivity. 29312209 5 59 theme time-series 667:677 arg1 analyses 679:686 time-series analyses 667:686 time-series analyses 667:686 Recently, modeling approaches such as genome-scale models and time-series analyses have been useful to predict microbial interactions. 29312209 7 60 theme microbiome 1028:1037 arg1 microorganisms 995:1008 four microorganisms 990:1008 four microorganisms of the infant gut microbiome (Bifidobacterium longum subsp 990:1067 The model was developed using experimental in vitro data from a system comprising four microorganisms of the infant gut microbiome (Bifidobacterium longum subsp. 29312209 17 61 theme microbial 2325:2333 arg1 consortia 2335:2343 microbial consortia 2325:2343 microbial consortia with desired properties such as higher acid production 2325:2398 Moreover, the model could be useful in designing microbial consortia with desired properties such as higher acid production. 29312209 7 62 theme infant 1017:1022 arg1 microbiome 1028:1037 the infant gut microbiome 1013:1037 the infant gut microbiome 1013:1037 The model was developed using experimental in vitro data from a system comprising four microorganisms of the infant gut microbiome (Bifidobacterium longum subsp. 29312209 1 63 theme microbial 110:118 arg1 community 120:128 a complex microbial community 100:128 a complex microbial community that has a significant influence on the host 100:173 The gut microbiome is a complex microbial community that has a significant influence on the host. 29312209 1 63 theme microbial 110:118 arg1 microbiome 86:95 The gut microbiome 78:95 The gut microbiome 78:95 The gut microbiome is a complex microbial community that has a significant influence on the host. 29312209 12 64 theme model 1582:1586 arg1 validation 1588:1597 Further model validation 1574:1597 Further model validation 1574:1597 Further model validation included cultures with the four-species in a bioreactor using FOS. 29312209 0 65 theme Gut 62:64 arg1 Microbiome 66:75 the Infant Gut Microbiome 51:75 the Infant Gut Microbiome 51:75 Modeling Metabolic Interactions in a Consortium of the Infant Gut Microbiome. 29312209 2 66 theme dietary 226:232 arg1 polysaccharides 265:279 complex polysaccharides 257:279 complex polysaccharides 257:279 Microbial interactions in the gut are mediated by dietary substrates, especially complex polysaccharides. 29312209 2 66 theme dietary 226:232 arg1 substrates 234:243 dietary substrates 226:243 dietary substrates 226:243 Microbial interactions in the gut are mediated by dietary substrates, especially complex polysaccharides. 29312209 3 67 theme larger 327:332 arg1 carbohydrates 334:346 larger carbohydrates 327:346 larger carbohydrates 327:346 In this environment, breakdown products from larger carbohydrates and short chain fatty acids are commonly shared among gut microbes. 29312209 10 68 theme predicted 1458:1466 arg1 consumption 1472:1482 predicted FOS consumption 1458:1482 predicted FOS consumption 1458:1482 In addition, a good correlation was observed between the experimental data with predicted FOS consumption and acid production. 29312209 7 69 from system 972:977 arg1 data 960:963 experimental in vitro data 938:963 experimental in vitro data from a system comprising four microorganisms of the infant gut microbiome (Bifidobacterium longum subsp 938:1067 The model was developed using experimental in vitro data from a system comprising four microorganisms of the infant gut microbiome (Bifidobacterium longum subsp. 29312209 7 70 dep in 951:952 arg1 vitro 954:958 vitro 954:958 vitro 954:958 The model was developed using experimental in vitro data from a system comprising four microorganisms of the infant gut microbiome (Bifidobacterium longum subsp. 29312209 16 71 from consortia 2147:2155 arg1 data 2130:2133 data 2130:2133 data from larger consortia 2130:2155 The model could be scaled to include data from larger consortia, or be applied to microbial communities where sharing metabolic resources is important in shaping bacterial abundance. 29312209 3 72 theme chain 358:362 arg1 acids 370:374 short chain fatty acids 352:374 short chain fatty acids 352:374 In this environment, breakdown products from larger carbohydrates and short chain fatty acids are commonly shared among gut microbes. 29312209 3 73 from acids 370:374 arg1 products 313:320 breakdown products 303:320 breakdown products from larger carbohydrates and short chain fatty acids 303:374 In this environment, breakdown products from larger carbohydrates and short chain fatty acids are commonly shared among gut microbes. 29312209 10 74 with data 1448:1451 arg1 consumption 1472:1482 predicted FOS consumption 1458:1482 predicted FOS consumption 1458:1482 In addition, a good correlation was observed between the experimental data with predicted FOS consumption and acid production. 29312209 10 74 with data 1448:1451 arg1 production 1493:1502 acid production 1488:1502 acid production 1488:1502 In addition, a good correlation was observed between the experimental data with predicted FOS consumption and acid production. 29312209 10 75 theme acid 1488:1491 arg1 production 1493:1502 acid production 1488:1502 acid production 1488:1502 In addition, a good correlation was observed between the experimental data with predicted FOS consumption and acid production. 29312209 0 76 theme Metabolic 9:17 arg1 Interactions 19:30 Modeling Metabolic Interactions 0:30 Modeling Metabolic Interactions 0:30 Modeling Metabolic Interactions in a Consortium of the Infant Gut Microbiome. 29312209 9 77 theme bacterial 1319:1327 arg1 abundance 1329:1337 bacterial abundance 1319:1337 bacterial abundance in co-cultures from mono-culture data 1319:1375 After parameter optimization, the model accurately predicted bacterial abundance in co-cultures from mono-culture data. 29312209 15 78 theme infant 1953:1958 arg1 gut 1960:1962 the infant gut 1949:1962 the infant gut 1949:1962 These results suggest that variations in microbial abundance and activities in the infant gut were mainly explained by metabolic interactions, and could be properly modeled using Monod kinetics with metabolic interactions. 29312209 7 79 theme experimental 938:949 arg1 data 960:963 experimental in vitro data 938:963 experimental in vitro data from a system comprising four microorganisms of the infant gut microbiome (Bifidobacterium longum subsp 938:1067 The model was developed using experimental in vitro data from a system comprising four microorganisms of the infant gut microbiome (Bifidobacterium longum subsp. 29312209 15 80 theme Monod 2049:2053 arg1 kinetics 2055:2062 Monod kinetics 2049:2062 Monod kinetics 2049:2062 These results suggest that variations in microbial abundance and activities in the infant gut were mainly explained by metabolic interactions, and could be properly modeled using Monod kinetics with metabolic interactions. 29312209 8 81 dep products 1226:1233 arg1 lactate 1248:1254 lactate 1248:1254 lactate 1248:1254 infantis, Lactobacillus acidophilus, Escherichia coli, and Bacteroides vulgatus), one substrate (fructooligosaccharides, FOS), and evaluating two metabolic products (acetate and lactate). 29312209 8 81 dep products 1226:1233 arg1 acetate 1236:1242 acetate 1236:1242 acetate 1236:1242 infantis, Lactobacillus acidophilus, Escherichia coli, and Bacteroides vulgatus), one substrate (fructooligosaccharides, FOS), and evaluating two metabolic products (acetate and lactate). 29312209 8 81 dep products 1226:1233 arg1 products 1226:1233 two metabolic products 1212:1233 two metabolic products (acetate and lactate) 1212:1255 infantis, Lactobacillus acidophilus, Escherichia coli, and Bacteroides vulgatus), one substrate (fructooligosaccharides, FOS), and evaluating two metabolic products (acetate and lactate). 29312209 7 82 dep microorganisms 995:1008 arg1 longum 1056:1061 Bifidobacterium longum 1040:1061 four microorganisms of the infant gut microbiome (Bifidobacterium longum subsp 990:1067 The model was developed using experimental in vitro data from a system comprising four microorganisms of the infant gut microbiome (Bifidobacterium longum subsp. 29312209 6 83 theme bottom-up 757:765 arg1 approach 767:774 a bottom-up approach 755:774 a bottom-up approach 755:774 In this study, a bottom-up approach was followed to develop a mathematical model based on microbial growth equations that incorporate metabolic sharing and inhibition. 29312209 12 84 from four-species 1626:1637 arg1 bioreactor 1644:1653 a bioreactor 1642:1653 a bioreactor using FOS 1642:1663 Further model validation included cultures with the four-species in a bioreactor using FOS. 29312209 16 85 from abundance 2265:2273 arg1 important 2234:2242 important 2234:2242 important 2234:2242 The model could be scaled to include data from larger consortia, or be applied to microbial communities where sharing metabolic resources is important in shaping bacterial abundance. 29312209 6 86 theme microbial 830:838 arg1 equations 847:855 microbial growth equations 830:855 microbial growth equations that incorporate metabolic sharing and inhibition 830:905 In this study, a bottom-up approach was followed to develop a mathematical model based on microbial growth equations that incorporate metabolic sharing and inhibition. 29312209 2 87 theme Microbial 176:184 arg1 interactions 186:197 Microbial interactions 176:197 Microbial interactions in the gut 176:208 Microbial interactions in the gut are mediated by dietary substrates, especially complex polysaccharides. 29312209 13 88 theme aforementioned 1724:1737 arg1 species 1739:1745 the two aforementioned species 1716:1745 the two aforementioned species 1716:1745 The model was able to predict the predominance of the two aforementioned species, as well as depletion of acetate and lactate. 29312209 10 89 located observed 1414:1421 arg1 addition 1381:1388 addition 1381:1388 addition 1381:1388 In addition, a good correlation was observed between the experimental data with predicted FOS consumption and acid production. 29312209 10 89 located observed 1414:1421 arg2 correlation 1398:1408 a good correlation 1391:1408 a good correlation 1391:1408 In addition, a good correlation was observed between the experimental data with predicted FOS consumption and acid production. 25130694 6 0 theme lesser 988:993 arg1 contributions 995:1007 lesser contributions 988:1007 lesser contributions from Proteobacteria 988:1027 Communities in all seasons were dominated by Firmicutes and Bacteroidetes, with lesser contributions from Proteobacteria, Verrucomicrobia, Tenericutes and Actinobacteria. 25130694 7 1 contain had 1091:1093 arg2 abundances 1110:1119 lower relative abundances 1095:1119 lower relative abundances of Firmicutes, which include genera that prefer plant polysaccharides, and higher abundances of Bacteroidetes and Verrucomicrobia, some of which can survive solely on host-derived mucins 1095:1306 Hibernators had lower relative abundances of Firmicutes, which include genera that prefer plant polysaccharides, and higher abundances of Bacteroidetes and Verrucomicrobia, some of which can survive solely on host-derived mucins. 25130694 7 1 contain had 1091:1093 arg1 Hibernators 1079:1089 Hibernators 1079:1089 Hibernators 1079:1089 Hibernators had lower relative abundances of Firmicutes, which include genera that prefer plant polysaccharides, and higher abundances of Bacteroidetes and Verrucomicrobia, some of which can survive solely on host-derived mucins. 25130694 7 2 theme Verrucomicrobia 1235:1249 arg1 abundances 1203:1212 higher abundances 1196:1212 higher abundances 1196:1212 Hibernators had lower relative abundances of Firmicutes, which include genera that prefer plant polysaccharides, and higher abundances of Bacteroidetes and Verrucomicrobia, some of which can survive solely on host-derived mucins. 25130694 7 2 theme Verrucomicrobia 1235:1249 arg1 polysaccharides 1175:1189 plant polysaccharides 1169:1189 plant polysaccharides 1169:1189 Hibernators had lower relative abundances of Firmicutes, which include genera that prefer plant polysaccharides, and higher abundances of Bacteroidetes and Verrucomicrobia, some of which can survive solely on host-derived mucins. 25130694 9 3 theme specific 1520:1527 arg1 taxa 1529:1532 specific taxa 1520:1532 specific taxa 1520:1532 This core community, together with moderate shifts in specific taxa, indicates that the mucosal microbiota remains relatively stable over the annual cycle yet responds to substrate changes while potentially serving as a pool for 'seeding' the microbiota once exogenous substrates return in spring. 25130694 7 4 theme Bacteroidetes 1217:1229 arg1 abundances 1203:1212 higher abundances 1196:1212 higher abundances 1196:1212 Hibernators had lower relative abundances of Firmicutes, which include genera that prefer plant polysaccharides, and higher abundances of Bacteroidetes and Verrucomicrobia, some of which can survive solely on host-derived mucins. 25130694 7 4 theme Bacteroidetes 1217:1229 arg1 polysaccharides 1175:1189 plant polysaccharides 1169:1189 plant polysaccharides 1169:1189 Hibernators had lower relative abundances of Firmicutes, which include genera that prefer plant polysaccharides, and higher abundances of Bacteroidetes and Verrucomicrobia, some of which can survive solely on host-derived mucins. 25130694 3 5 theme ground 588:593 arg1 squirrels 595:603 13-lined ground squirrels 579:603 13-lined ground squirrels 579:603 We used 16S rRNA pyrosequencing and caecal tissue protein analysis to investigate the effects of hibernation on the mucosa-associated bacterial microbiota and host responses in 13-lined ground squirrels. 25130694 4 6 theme summer 704:709 arg1 squirrels 711:719 summer squirrels 704:719 summer squirrels 704:719 The mucosal microbiota was less diverse in winter hibernators than in actively feeding spring and summer squirrels. 25130694 1 7 theme important 183:191 arg1 roles 193:197 important roles 183:197 important roles 183:197 The gut microbiota plays important roles in animal nutrition and health. 25130694 8 8 theme units 1365:1369 arg1 assemblage 1324:1333 A core mucosal assemblage 1309:1333 A core mucosal assemblage of nine operational taxonomic units shared among all individuals 1309:1398 A core mucosal assemblage of nine operational taxonomic units shared among all individuals was identified with an average total sequence abundance of 60.2%. 25130694 11 9 theme caecal 1909:1914 arg1 TLR4 1916:1919 caecal TLR4 1909:1919 caecal TLR4 1909:1919 Hibernation also decreased caecal TLR4 and increased TLR5 expression, suggesting a protective response that minimizes inflammation. 25130694 4 10 from spring 693:698 arg1 microbiota 618:627 The mucosal microbiota 606:627 The mucosal microbiota 606:627 The mucosal microbiota was less diverse in winter hibernators than in actively feeding spring and summer squirrels. 25130694 4 10 from spring 693:698 arg1 diverse 638:644 diverse 638:644 diverse 638:644 The mucosal microbiota was less diverse in winter hibernators than in actively feeding spring and summer squirrels. 25130694 9 11 theme mucosal 1554:1560 arg1 microbiota 1562:1571 the mucosal microbiota 1550:1571 the mucosal microbiota 1550:1571 This core community, together with moderate shifts in specific taxa, indicates that the mucosal microbiota remains relatively stable over the annual cycle yet responds to substrate changes while potentially serving as a pool for 'seeding' the microbiota once exogenous substrates return in spring. 25130694 5 12 with consistent 861:870 arg1 structures 896:905 their transitional structures 877:905 their transitional structures 877:905 UniFrac analysis revealed distinct summer and late winter microbiota clusters, while spring and early winter clusters overlapped slightly, consistent with their transitional structures. 25130694 8 13 theme mucosal 1316:1322 arg1 assemblage 1324:1333 A core mucosal assemblage 1309:1333 A core mucosal assemblage of nine operational taxonomic units shared among all individuals 1309:1398 A core mucosal assemblage of nine operational taxonomic units shared among all individuals was identified with an average total sequence abundance of 60.2%. 25130694 11 14 theme TLR5 1935:1938 arg1 expression 1940:1949 increased TLR5 expression 1925:1949 increased TLR5 expression 1925:1949 Hibernation also decreased caecal TLR4 and increased TLR5 expression, suggesting a protective response that minimizes inflammation. 25130694 5 15 theme winter 773:778 arg1 clusters 791:798 distinct summer and late winter microbiota clusters 748:798 distinct summer and late winter microbiota clusters 748:798 UniFrac analysis revealed distinct summer and late winter microbiota clusters, while spring and early winter clusters overlapped slightly, consistent with their transitional structures. 25130694 6 16 from Communities 908:918 arg1 seasons 927:933 all seasons 923:933 all seasons 923:933 Communities in all seasons were dominated by Firmicutes and Bacteroidetes, with lesser contributions from Proteobacteria, Verrucomicrobia, Tenericutes and Actinobacteria. 25130694 7 17 theme relative 1101:1108 arg1 abundances 1110:1119 lower relative abundances 1095:1119 lower relative abundances of Firmicutes, which include genera that prefer plant polysaccharides, and higher abundances of Bacteroidetes and Verrucomicrobia, some of which can survive solely on host-derived mucins 1095:1306 Hibernators had lower relative abundances of Firmicutes, which include genera that prefer plant polysaccharides, and higher abundances of Bacteroidetes and Verrucomicrobia, some of which can survive solely on host-derived mucins. 25130694 5 18 theme distinct 748:755 arg1 clusters 791:798 distinct summer and late winter microbiota clusters 748:798 distinct summer and late winter microbiota clusters 748:798 UniFrac analysis revealed distinct summer and late winter microbiota clusters, while spring and early winter clusters overlapped slightly, consistent with their transitional structures. 25130694 7 19 link host-derived 1288:1299 arg1 mucins 1301:1306 host-derived mucins 1288:1306 host-derived mucins 1288:1306 Hibernators had lower relative abundances of Firmicutes, which include genera that prefer plant polysaccharides, and higher abundances of Bacteroidetes and Verrucomicrobia, some of which can survive solely on host-derived mucins. 25130694 0 20 from defence 109:115 arg1 gut 124:126 the gut 120:126 the gut of 13-lined ground squirrels 120:155 Hibernation alters the diversity and composition of mucosa-associated bacteria while enhancing antimicrobial defence in the gut of 13-lined ground squirrels. 25130694 8 21 theme total 1431:1435 arg1 abundance 1446:1454 an average total sequence abundance 1420:1454 an average total sequence abundance of 60.2% 1420:1463 A core mucosal assemblage of nine operational taxonomic units shared among all individuals was identified with an average total sequence abundance of 60.2%. 25130694 10 22 from expression 1843:1852 arg1 spring 1874:1879 spring 1874:1879 spring 1874:1879 Relative to summer, hibernation reduced caecal crypt length and increased MUC2 expression in early winter and spring. 25130694 10 22 from expression 1843:1852 arg1 winter 1863:1868 early winter 1857:1868 early winter 1857:1868 Relative to summer, hibernation reduced caecal crypt length and increased MUC2 expression in early winter and spring. 25130694 0 23 theme bacteria 70:77 arg1 composition 37:47 composition 37:47 composition 37:47 Hibernation alters the diversity and composition of mucosa-associated bacteria while enhancing antimicrobial defence in the gut of 13-lined ground squirrels. 25130694 0 23 theme bacteria 70:77 arg1 diversity 23:31 diversity 23:31 diversity 23:31 Hibernation alters the diversity and composition of mucosa-associated bacteria while enhancing antimicrobial defence in the gut of 13-lined ground squirrels. 25130694 5 24 theme winter 824:829 arg1 clusters 831:838 spring and early winter clusters 807:838 spring and early winter clusters 807:838 UniFrac analysis revealed distinct summer and late winter microbiota clusters, while spring and early winter clusters overlapped slightly, consistent with their transitional structures. 25130694 9 25 theme substrate 1637:1645 arg1 changes 1647:1653 substrate changes 1637:1653 substrate changes 1637:1653 This core community, together with moderate shifts in specific taxa, indicates that the mucosal microbiota remains relatively stable over the annual cycle yet responds to substrate changes while potentially serving as a pool for 'seeding' the microbiota once exogenous substrates return in spring. 25130694 0 26 theme squirrels 147:155 arg1 gut 124:126 the gut 120:126 the gut of 13-lined ground squirrels 120:155 Hibernation alters the diversity and composition of mucosa-associated bacteria while enhancing antimicrobial defence in the gut of 13-lined ground squirrels. 25130694 10 27 theme early 1857:1861 arg1 winter 1863:1868 early winter 1857:1868 early winter 1857:1868 Relative to summer, hibernation reduced caecal crypt length and increased MUC2 expression in early winter and spring. 25130694 3 28 theme tissue 445:450 arg1 analysis 460:467 caecal tissue protein analysis 438:467 caecal tissue protein analysis 438:467 We used 16S rRNA pyrosequencing and caecal tissue protein analysis to investigate the effects of hibernation on the mucosa-associated bacterial microbiota and host responses in 13-lined ground squirrels. 25130694 3 29 dep microbiota 546:555 arg1 the 514:516 the 514:516 the 514:516 We used 16S rRNA pyrosequencing and caecal tissue protein analysis to investigate the effects of hibernation on the mucosa-associated bacterial microbiota and host responses in 13-lined ground squirrels. 25130694 2 30 from dynamic 265:271 arg1 mammals 288:294 hibernating mammals 276:294 hibernating mammals where fasting drives the gut community to rely on host-derived nutrients instead of exogenous substrates 276:399 This relationship is particularly dynamic in hibernating mammals where fasting drives the gut community to rely on host-derived nutrients instead of exogenous substrates. 25130694 5 31 theme transitional 883:894 arg1 structures 896:905 their transitional structures 877:905 their transitional structures 877:905 UniFrac analysis revealed distinct summer and late winter microbiota clusters, while spring and early winter clusters overlapped slightly, consistent with their transitional structures. 25130694 8 32 theme operational 1343:1353 arg1 units 1365:1369 nine operational taxonomic units 1338:1369 nine operational taxonomic units shared among all individuals 1338:1398 A core mucosal assemblage of nine operational taxonomic units shared among all individuals was identified with an average total sequence abundance of 60.2%. 25130694 3 33 used used 405:408 arg2 We 402:403 We 402:403 We 402:403 We used 16S rRNA pyrosequencing and caecal tissue protein analysis to investigate the effects of hibernation on the mucosa-associated bacterial microbiota and host responses in 13-lined ground squirrels. 25130694 9 34 theme seeding 1696:1702 arg1 return 1746:1751 'seeding' the microbiota once exogenous substrates return 1695:1751 'seeding' the microbiota once exogenous substrates return in spring 1695:1761 This core community, together with moderate shifts in specific taxa, indicates that the mucosal microbiota remains relatively stable over the annual cycle yet responds to substrate changes while potentially serving as a pool for 'seeding' the microbiota once exogenous substrates return in spring. 25130694 3 35 theme rRNA 414:417 arg1 pyrosequencing 419:432 16S rRNA pyrosequencing 410:432 16S rRNA pyrosequencing 410:432 We used 16S rRNA pyrosequencing and caecal tissue protein analysis to investigate the effects of hibernation on the mucosa-associated bacterial microbiota and host responses in 13-lined ground squirrels. 25130694 6 36 from Proteobacteria 1014:1027 arg1 contributions 995:1007 lesser contributions 988:1007 lesser contributions from Proteobacteria 988:1027 Communities in all seasons were dominated by Firmicutes and Bacteroidetes, with lesser contributions from Proteobacteria, Verrucomicrobia, Tenericutes and Actinobacteria. 25130694 4 37 from hibernators 656:666 arg1 microbiota 618:627 The mucosal microbiota 606:627 The mucosal microbiota 606:627 The mucosal microbiota was less diverse in winter hibernators than in actively feeding spring and summer squirrels. 25130694 4 37 from hibernators 656:666 arg1 diverse 638:644 diverse 638:644 diverse 638:644 The mucosal microbiota was less diverse in winter hibernators than in actively feeding spring and summer squirrels. 25130694 10 38 theme crypt 1811:1815 arg1 length 1817:1822 caecal crypt length 1804:1822 caecal crypt length 1804:1822 Relative to summer, hibernation reduced caecal crypt length and increased MUC2 expression in early winter and spring. 25130694 9 39 from shifts 1510:1515 arg1 taxa 1529:1532 specific taxa 1520:1532 specific taxa 1520:1532 This core community, together with moderate shifts in specific taxa, indicates that the mucosal microbiota remains relatively stable over the annual cycle yet responds to substrate changes while potentially serving as a pool for 'seeding' the microbiota once exogenous substrates return in spring. 25130694 3 40 theme hibernation 499:509 arg1 effects 488:494 the effects 484:494 the effects of hibernation on the mucosa-associated bacterial microbiota and host responses in 13-lined ground squirrels 484:603 We used 16S rRNA pyrosequencing and caecal tissue protein analysis to investigate the effects of hibernation on the mucosa-associated bacterial microbiota and host responses in 13-lined ground squirrels. 25130694 10 41 theme caecal 1804:1809 arg1 length 1817:1822 caecal crypt length 1804:1822 caecal crypt length 1804:1822 Relative to summer, hibernation reduced caecal crypt length and increased MUC2 expression in early winter and spring. 25130694 10 42 theme MUC2 1838:1841 arg1 expression 1843:1852 MUC2 expression 1838:1852 MUC2 expression in early winter and spring 1838:1879 Relative to summer, hibernation reduced caecal crypt length and increased MUC2 expression in early winter and spring. 25130694 9 43 theme moderate 1501:1508 arg1 shifts 1510:1515 moderate shifts 1501:1515 moderate shifts in specific taxa 1501:1532 This core community, together with moderate shifts in specific taxa, indicates that the mucosal microbiota remains relatively stable over the annual cycle yet responds to substrate changes while potentially serving as a pool for 'seeding' the microbiota once exogenous substrates return in spring. 25130694 5 44 theme early 818:822 arg1 winter 824:829 early winter 818:829 early winter 818:829 UniFrac analysis revealed distinct summer and late winter microbiota clusters, while spring and early winter clusters overlapped slightly, consistent with their transitional structures. 25130694 3 45 theme bacterial 536:544 arg1 microbiota 546:555 mucosa-associated bacterial microbiota 518:555 mucosa-associated bacterial microbiota 518:555 We used 16S rRNA pyrosequencing and caecal tissue protein analysis to investigate the effects of hibernation on the mucosa-associated bacterial microbiota and host responses in 13-lined ground squirrels. 25130694 2 46 link host-derived 346:357 arg1 nutrients 359:367 host-derived nutrients 346:367 host-derived nutrients instead of exogenous substrates 346:399 This relationship is particularly dynamic in hibernating mammals where fasting drives the gut community to rely on host-derived nutrients instead of exogenous substrates. 25130694 3 47 from microbiota 546:555 arg1 squirrels 595:603 13-lined ground squirrels 579:603 13-lined ground squirrels 579:603 We used 16S rRNA pyrosequencing and caecal tissue protein analysis to investigate the effects of hibernation on the mucosa-associated bacterial microbiota and host responses in 13-lined ground squirrels. 25130694 3 48 theme 13-lined 579:586 arg1 squirrels 595:603 13-lined ground squirrels 579:603 13-lined ground squirrels 579:603 We used 16S rRNA pyrosequencing and caecal tissue protein analysis to investigate the effects of hibernation on the mucosa-associated bacterial microbiota and host responses in 13-lined ground squirrels. 25130694 7 49 theme higher 1196:1201 arg1 abundances 1203:1212 higher abundances 1196:1212 higher abundances 1196:1212 Hibernators had lower relative abundances of Firmicutes, which include genera that prefer plant polysaccharides, and higher abundances of Bacteroidetes and Verrucomicrobia, some of which can survive solely on host-derived mucins. 25130694 4 50 from squirrels 711:719 arg1 microbiota 618:627 The mucosal microbiota 606:627 The mucosal microbiota 606:627 The mucosal microbiota was less diverse in winter hibernators than in actively feeding spring and summer squirrels. 25130694 4 50 from squirrels 711:719 arg1 diverse 638:644 diverse 638:644 diverse 638:644 The mucosal microbiota was less diverse in winter hibernators than in actively feeding spring and summer squirrels. 25130694 8 51 theme taxonomic 1355:1363 arg1 units 1365:1369 nine operational taxonomic units 1338:1369 nine operational taxonomic units shared among all individuals 1338:1398 A core mucosal assemblage of nine operational taxonomic units shared among all individuals was identified with an average total sequence abundance of 60.2%. 25130694 7 52 theme plant 1169:1173 arg1 polysaccharides 1175:1189 plant polysaccharides 1169:1189 plant polysaccharides 1169:1189 Hibernators had lower relative abundances of Firmicutes, which include genera that prefer plant polysaccharides, and higher abundances of Bacteroidetes and Verrucomicrobia, some of which can survive solely on host-derived mucins. 25130694 2 53 theme gut 321:323 arg1 community 325:333 the gut community 317:333 the gut community 317:333 This relationship is particularly dynamic in hibernating mammals where fasting drives the gut community to rely on host-derived nutrients instead of exogenous substrates. 25130694 1 54 theme animal 202:207 arg1 nutrition 209:217 animal nutrition 202:217 animal nutrition 202:217 The gut microbiota plays important roles in animal nutrition and health. 25130694 2 55 theme host-derived 346:357 arg1 nutrients 359:367 host-derived nutrients 346:367 host-derived nutrients instead of exogenous substrates 346:399 This relationship is particularly dynamic in hibernating mammals where fasting drives the gut community to rely on host-derived nutrients instead of exogenous substrates. 25130694 5 56 theme late 768:771 arg1 clusters 791:798 distinct summer and late winter microbiota clusters 748:798 distinct summer and late winter microbiota clusters 748:798 UniFrac analysis revealed distinct summer and late winter microbiota clusters, while spring and early winter clusters overlapped slightly, consistent with their transitional structures. 25130694 9 57 dep seeding 1696:1702 arg1 microbiota 1709:1718 the microbiota 1705:1718 'seeding' the microbiota once exogenous substrates return in spring 1695:1761 This core community, together with moderate shifts in specific taxa, indicates that the mucosal microbiota remains relatively stable over the annual cycle yet responds to substrate changes while potentially serving as a pool for 'seeding' the microbiota once exogenous substrates return in spring. 25130694 8 58 theme core 1311:1314 arg1 assemblage 1324:1333 A core mucosal assemblage 1309:1333 A core mucosal assemblage of nine operational taxonomic units shared among all individuals 1309:1398 A core mucosal assemblage of nine operational taxonomic units shared among all individuals was identified with an average total sequence abundance of 60.2%. 25130694 6 59 dep Verrucomicrobia 1030:1044 arg1 Bacteroidetes 968:980 Bacteroidetes, with lesser contributions from Proteobacteria, Verrucomicrobia, Tenericutes and Actinobacteria 968:1076 Bacteroidetes 968:980 Communities in all seasons were dominated by Firmicutes and Bacteroidetes, with lesser contributions from Proteobacteria, Verrucomicrobia, Tenericutes and Actinobacteria. 25130694 4 60 theme feeding 685:691 arg1 spring 693:698 actively feeding spring 676:698 actively feeding spring 676:698 The mucosal microbiota was less diverse in winter hibernators than in actively feeding spring and summer squirrels. 25130694 5 61 theme microbiota 780:789 arg1 clusters 791:798 distinct summer and late winter microbiota clusters 748:798 distinct summer and late winter microbiota clusters 748:798 UniFrac analysis revealed distinct summer and late winter microbiota clusters, while spring and early winter clusters overlapped slightly, consistent with their transitional structures. 25130694 5 62 theme UniFrac 722:728 arg1 analysis 730:737 UniFrac analysis 722:737 UniFrac analysis 722:737 UniFrac analysis revealed distinct summer and late winter microbiota clusters, while spring and early winter clusters overlapped slightly, consistent with their transitional structures. 25130694 7 63 theme Firmicutes 1124:1133 arg1 abundances 1110:1119 lower relative abundances 1095:1119 lower relative abundances of Firmicutes, which include genera that prefer plant polysaccharides, and higher abundances of Bacteroidetes and Verrucomicrobia, some of which can survive solely on host-derived mucins 1095:1306 Hibernators had lower relative abundances of Firmicutes, which include genera that prefer plant polysaccharides, and higher abundances of Bacteroidetes and Verrucomicrobia, some of which can survive solely on host-derived mucins. 25130694 9 64 from return 1746:1751 arg1 spring 1756:1761 spring 1756:1761 spring 1756:1761 This core community, together with moderate shifts in specific taxa, indicates that the mucosal microbiota remains relatively stable over the annual cycle yet responds to substrate changes while potentially serving as a pool for 'seeding' the microbiota once exogenous substrates return in spring. 25130694 0 65 theme 13-lined 131:138 arg1 squirrels 147:155 13-lined ground squirrels 131:155 13-lined ground squirrels 131:155 Hibernation alters the diversity and composition of mucosa-associated bacteria while enhancing antimicrobial defence in the gut of 13-lined ground squirrels. 25130694 11 66 theme increased 1925:1933 arg1 expression 1940:1949 increased TLR5 expression 1925:1949 increased TLR5 expression 1925:1949 Hibernation also decreased caecal TLR4 and increased TLR5 expression, suggesting a protective response that minimizes inflammation. 25130694 2 67 theme hibernating 276:286 arg1 mammals 288:294 hibernating mammals 276:294 hibernating mammals where fasting drives the gut community to rely on host-derived nutrients instead of exogenous substrates 276:399 This relationship is particularly dynamic in hibernating mammals where fasting drives the gut community to rely on host-derived nutrients instead of exogenous substrates. 25130694 9 68 theme annual 1608:1613 arg1 cycle 1615:1619 the annual cycle 1604:1619 the annual cycle 1604:1619 This core community, together with moderate shifts in specific taxa, indicates that the mucosal microbiota remains relatively stable over the annual cycle yet responds to substrate changes while potentially serving as a pool for 'seeding' the microbiota once exogenous substrates return in spring. 25130694 2 69 from mammals 288:294 arg1 dynamic 265:271 dynamic 265:271 dynamic 265:271 This relationship is particularly dynamic in hibernating mammals where fasting drives the gut community to rely on host-derived nutrients instead of exogenous substrates. 25130694 5 70 theme spring 807:812 arg1 clusters 831:838 spring and early winter clusters 807:838 spring and early winter clusters 807:838 UniFrac analysis revealed distinct summer and late winter microbiota clusters, while spring and early winter clusters overlapped slightly, consistent with their transitional structures. 25130694 7 71 theme lower 1095:1099 arg1 abundances 1110:1119 lower relative abundances 1095:1119 lower relative abundances of Firmicutes, which include genera that prefer plant polysaccharides, and higher abundances of Bacteroidetes and Verrucomicrobia, some of which can survive solely on host-derived mucins 1095:1306 Hibernators had lower relative abundances of Firmicutes, which include genera that prefer plant polysaccharides, and higher abundances of Bacteroidetes and Verrucomicrobia, some of which can survive solely on host-derived mucins. 25130694 5 72 theme summer 757:762 arg1 clusters 791:798 distinct summer and late winter microbiota clusters 748:798 distinct summer and late winter microbiota clusters 748:798 UniFrac analysis revealed distinct summer and late winter microbiota clusters, while spring and early winter clusters overlapped slightly, consistent with their transitional structures. 25130694 8 73 theme average 1423:1429 arg1 abundance 1446:1454 an average total sequence abundance 1420:1454 an average total sequence abundance of 60.2% 1420:1463 A core mucosal assemblage of nine operational taxonomic units shared among all individuals was identified with an average total sequence abundance of 60.2%. 25130694 3 74 from responses 566:574 arg1 squirrels 595:603 13-lined ground squirrels 579:603 13-lined ground squirrels 579:603 We used 16S rRNA pyrosequencing and caecal tissue protein analysis to investigate the effects of hibernation on the mucosa-associated bacterial microbiota and host responses in 13-lined ground squirrels. 25130694 0 75 theme antimicrobial 95:107 arg1 defence 109:115 antimicrobial defence 95:115 antimicrobial defence in the gut of 13-lined ground squirrels 95:155 Hibernation alters the diversity and composition of mucosa-associated bacteria while enhancing antimicrobial defence in the gut of 13-lined ground squirrels. 25130694 1 76 theme gut 162:164 arg1 microbiota 166:175 The gut microbiota 158:175 The gut microbiota 158:175 The gut microbiota plays important roles in animal nutrition and health. 25130694 8 77 theme sequence 1437:1444 arg1 abundance 1446:1454 an average total sequence abundance 1420:1454 an average total sequence abundance of 60.2% 1420:1463 A core mucosal assemblage of nine operational taxonomic units shared among all individuals was identified with an average total sequence abundance of 60.2%. 25130694 4 78 from diverse 638:644 arg1 hibernators 656:666 winter hibernators 649:666 winter hibernators 649:666 The mucosal microbiota was less diverse in winter hibernators than in actively feeding spring and summer squirrels. 25130694 4 78 from diverse 638:644 arg1 spring 693:698 actively feeding spring 676:698 actively feeding spring 676:698 The mucosal microbiota was less diverse in winter hibernators than in actively feeding spring and summer squirrels. 25130694 4 78 from diverse 638:644 arg1 squirrels 711:719 summer squirrels 704:719 summer squirrels 704:719 The mucosal microbiota was less diverse in winter hibernators than in actively feeding spring and summer squirrels. 25130694 7 79 theme host-derived 1288:1299 arg1 mucins 1301:1306 host-derived mucins 1288:1306 host-derived mucins 1288:1306 Hibernators had lower relative abundances of Firmicutes, which include genera that prefer plant polysaccharides, and higher abundances of Bacteroidetes and Verrucomicrobia, some of which can survive solely on host-derived mucins. 25130694 8 80 theme % 1463:1463 arg1 abundance 1446:1454 an average total sequence abundance 1420:1454 an average total sequence abundance of 60.2% 1420:1463 A core mucosal assemblage of nine operational taxonomic units shared among all individuals was identified with an average total sequence abundance of 60.2%. 25130694 3 81 theme 16S 410:412 arg1 rRNA 414:417 16S rRNA 410:417 16S rRNA pyrosequencing 410:432 We used 16S rRNA pyrosequencing and caecal tissue protein analysis to investigate the effects of hibernation on the mucosa-associated bacterial microbiota and host responses in 13-lined ground squirrels. 25130694 3 82 theme protein 452:458 arg1 analysis 460:467 caecal tissue protein analysis 438:467 caecal tissue protein analysis 438:467 We used 16S rRNA pyrosequencing and caecal tissue protein analysis to investigate the effects of hibernation on the mucosa-associated bacterial microbiota and host responses in 13-lined ground squirrels. 25130694 4 83 theme mucosal 610:616 arg1 microbiota 618:627 The mucosal microbiota 606:627 The mucosal microbiota 606:627 The mucosal microbiota was less diverse in winter hibernators than in actively feeding spring and summer squirrels. 25130694 4 83 theme mucosal 610:616 arg1 diverse 638:644 diverse 638:644 diverse 638:644 The mucosal microbiota was less diverse in winter hibernators than in actively feeding spring and summer squirrels. 25130694 3 84 theme caecal 438:443 arg1 analysis 460:467 caecal tissue protein analysis 438:467 caecal tissue protein analysis 438:467 We used 16S rRNA pyrosequencing and caecal tissue protein analysis to investigate the effects of hibernation on the mucosa-associated bacterial microbiota and host responses in 13-lined ground squirrels. 25130694 0 85 theme mucosa-associated 52:68 arg1 bacteria 70:77 mucosa-associated bacteria 52:77 mucosa-associated bacteria 52:77 Hibernation alters the diversity and composition of mucosa-associated bacteria while enhancing antimicrobial defence in the gut of 13-lined ground squirrels. 25130694 9 86 theme core 1471:1474 arg1 community 1476:1484 This core community 1466:1484 This core community 1466:1484 This core community, together with moderate shifts in specific taxa, indicates that the mucosal microbiota remains relatively stable over the annual cycle yet responds to substrate changes while potentially serving as a pool for 'seeding' the microbiota once exogenous substrates return in spring. 25130694 0 87 theme ground 140:145 arg1 squirrels 147:155 13-lined ground squirrels 131:155 13-lined ground squirrels 131:155 Hibernation alters the diversity and composition of mucosa-associated bacteria while enhancing antimicrobial defence in the gut of 13-lined ground squirrels. 25130694 3 88 from effects 488:494 arg1 microbiota 546:555 mucosa-associated bacterial microbiota 518:555 mucosa-associated bacterial microbiota 518:555 We used 16S rRNA pyrosequencing and caecal tissue protein analysis to investigate the effects of hibernation on the mucosa-associated bacterial microbiota and host responses in 13-lined ground squirrels. 25130694 3 88 from effects 488:494 arg1 responses 566:574 host responses 561:574 host responses 561:574 We used 16S rRNA pyrosequencing and caecal tissue protein analysis to investigate the effects of hibernation on the mucosa-associated bacterial microbiota and host responses in 13-lined ground squirrels. 25130694 3 89 theme mucosa-associated 518:534 arg1 microbiota 546:555 mucosa-associated bacterial microbiota 518:555 mucosa-associated bacterial microbiota 518:555 We used 16S rRNA pyrosequencing and caecal tissue protein analysis to investigate the effects of hibernation on the mucosa-associated bacterial microbiota and host responses in 13-lined ground squirrels. 25130694 11 90 theme protective 1965:1974 arg1 response 1976:1983 a protective response 1963:1983 a protective response that minimizes inflammation 1963:2011 Hibernation also decreased caecal TLR4 and increased TLR5 expression, suggesting a protective response that minimizes inflammation. 25130694 0 91 dep diversity 23:31 arg1 the 19:21 the 19:21 the 19:21 Hibernation alters the diversity and composition of mucosa-associated bacteria while enhancing antimicrobial defence in the gut of 13-lined ground squirrels. 25130694 4 92 theme winter 649:654 arg1 hibernators 656:666 winter hibernators 649:666 winter hibernators 649:666 The mucosal microbiota was less diverse in winter hibernators than in actively feeding spring and summer squirrels. 25130694 3 93 theme host 561:564 arg1 responses 566:574 host responses 561:574 host responses 561:574 We used 16S rRNA pyrosequencing and caecal tissue protein analysis to investigate the effects of hibernation on the mucosa-associated bacterial microbiota and host responses in 13-lined ground squirrels. 25130694 9 94 theme exogenous 1725:1733 arg1 substrates 1735:1744 exogenous substrates 1725:1744 exogenous substrates 1725:1744 This core community, together with moderate shifts in specific taxa, indicates that the mucosal microbiota remains relatively stable over the annual cycle yet responds to substrate changes while potentially serving as a pool for 'seeding' the microbiota once exogenous substrates return in spring. 25130694 2 95 theme exogenous 380:388 arg1 substrates 390:399 exogenous substrates 380:399 host-derived nutrients instead of exogenous substrates 346:399 This relationship is particularly dynamic in hibernating mammals where fasting drives the gut community to rely on host-derived nutrients instead of exogenous substrates. 25124934 12 0 theme haloarchaeal 2084:2095 arg1 species 2097:2103 haloarchaeal species 2084:2103 haloarchaeal species 2084:2103 CONCLUSIONS The developmental processes, functional properties and dynamics of H. volcanii biofilms provide insight on how haloarchaeal species might persist, interact and exchange DNA in natural communities. 25124934 14 1 theme genetic 2571:2577 arg1 processes 2597:2605 genetic and developmental processes 2571:2605 genetic and developmental processes 2571:2605 Because H. volcanii has one of the most advanced genetic systems for any archaeon, the phenotypes reported here may promote the study of genetic and developmental processes in archaeal biofilms. 25124934 11 2 theme mating 1897:1902 arg1 frequency 1904:1912 the mating frequency 1893:1912 the mating frequency of a classic filter-based experimental method 1893:1958 Finally, we quantified gene exchange between biofilm cells, and found that it was equivalent to the mating frequency of a classic filter-based experimental method. 25124934 3 3 theme biogeochemical 545:558 arg1 systems 560:566 ecological and biogeochemical systems 530:566 ecological and biogeochemical systems 530:566 Like bacteria, archaea impact ecological and biogeochemical systems. 25124934 6 4 theme cell 846:849 arg1 dyes 860:863 fluorescent cell membrane dyes 834:863 fluorescent cell membrane dyes 834:863 RESULTS Biofilms were cultured in static liquid and visualized with fluorescent cell membrane dyes and by engineering cells to express green fluorescent protein (GFP). 25124934 9 5 theme disk-shaped 1683:1693 arg1 morphology 1695:1704 their planktonic disk-shaped morphology 1666:1704 their planktonic disk-shaped morphology 1666:1704 Following a switch to biofilm growth conditions, a sub-population of cells differentiated into chains of long rods sometimes exceeding 25 μm in length, compared to their planktonic disk-shaped morphology. 25124934 10 6 theme social 1780:1785 arg1 motility 1787:1794 wave-like social motility 1770:1794 wave-like social motility 1770:1794 Time-lapse photography of static liquid biofilms also revealed wave-like social motility. 25124934 1 7 theme microbial 181:189 arg1 lifestyle 191:199 a similar microbial lifestyle 171:199 a similar microbial lifestyle 171:199 BACKGROUND Archaea share a similar microbial lifestyle with bacteria, and not surprisingly then, also exist within matrix-enclosed communities known as biofilms. 25124934 8 8 theme extracellular 1192:1204 arg1 matrix 1206:1211 the extracellular matrix 1188:1211 the extracellular matrix 1188:1211 To visualize the extracellular matrix, biofilms formed by GFP-expressing cells were stained with concanavalin A, DAPI, Congo red and thioflavin T. Stains colocalized with larger cellular structures and indicated that the extracellular matrix may contain a combination of polysaccharides, extracellular DNA and amyloid protein. 25124934 14 9 theme genetic 2483:2489 arg1 systems 2491:2497 the most advanced genetic systems 2465:2497 the most advanced genetic systems 2465:2497 Because H. volcanii has one of the most advanced genetic systems for any archaeon, the phenotypes reported here may promote the study of genetic and developmental processes in archaeal biofilms. 25124934 11 10 theme biofilm 1842:1848 arg1 cells 1850:1854 biofilm cells 1842:1854 biofilm cells 1842:1854 Finally, we quantified gene exchange between biofilm cells, and found that it was equivalent to the mating frequency of a classic filter-based experimental method. 25124934 7 11 theme flake-like 1107:1116 arg1 towers 1118:1123 flake-like towers 1107:1123 flake-like towers often greater than 100 μm in height 1107:1159 Analysis by confocal scanning laser microscopy showed that H. volcanii cells formed microcolonies within 24 h, which developed into larger clusters by 48 h and matured into flake-like towers often greater than 100 μm in height after 7 days. 25124934 2 12 theme biofilm 320:326 arg1 biology 328:334 biofilm biology 320:334 biofilm biology 320:334 Advances in biofilm biology have been made over decades for model bacterial species, and include characterizations of social behaviors and cellular differentiation during biofilm development. 25124934 12 13 theme natural 2149:2155 arg1 communities 2157:2167 natural communities 2149:2167 natural communities 2149:2167 CONCLUSIONS The developmental processes, functional properties and dynamics of H. volcanii biofilms provide insight on how haloarchaeal species might persist, interact and exchange DNA in natural communities. 25124934 5 14 theme haloarchaeon 729:740 arg1 volcanii 752:759 the haloarchaeon Haloferax volcanii 725:759 the haloarchaeon Haloferax volcanii DS2 725:763 Here, we investigated the development, composition and dynamics of biofilms formed by the haloarchaeon Haloferax volcanii DS2. 25124934 10 15 theme biofilms 1747:1754 arg1 photography 1718:1728 Time-lapse photography 1707:1728 Time-lapse photography of static liquid biofilms 1707:1754 Time-lapse photography of static liquid biofilms also revealed wave-like social motility. 25124934 12 16 dep CONCLUSIONS 1961:1971 arg1 provide 2061:2067 provide 2061:2067 provide insight on how haloarchaeal species might persist 2061:2117 CONCLUSIONS The developmental processes, functional properties and dynamics of H. volcanii biofilms provide insight on how haloarchaeal species might persist, interact and exchange DNA in natural communities. 25124934 12 16 dep CONCLUSIONS 1961:1971 arg1 interact 2120:2127 interact 2120:2127 interact 2120:2127 CONCLUSIONS The developmental processes, functional properties and dynamics of H. volcanii biofilms provide insight on how haloarchaeal species might persist, interact and exchange DNA in natural communities. 25124934 12 16 dep CONCLUSIONS 1961:1971 arg1 DNA 2142:2144 exchange DNA 2133:2144 exchange DNA 2133:2144 CONCLUSIONS The developmental processes, functional properties and dynamics of H. volcanii biofilms provide insight on how haloarchaeal species might persist, interact and exchange DNA in natural communities. 25124934 5 17 theme volcanii 752:759 arg1 DS2 761:763 the haloarchaeon Haloferax volcanii DS2 725:763 the haloarchaeon Haloferax volcanii DS2 725:763 Here, we investigated the development, composition and dynamics of biofilms formed by the haloarchaeon Haloferax volcanii DS2. 25124934 12 18 from DNA 2142:2144 arg1 communities 2157:2167 natural communities 2149:2167 natural communities 2149:2167 CONCLUSIONS The developmental processes, functional properties and dynamics of H. volcanii biofilms provide insight on how haloarchaeal species might persist, interact and exchange DNA in natural communities. 25124934 12 19 theme functional 2002:2011 arg1 properties 2013:2022 functional properties 2002:2022 functional properties 2002:2022 CONCLUSIONS The developmental processes, functional properties and dynamics of H. volcanii biofilms provide insight on how haloarchaeal species might persist, interact and exchange DNA in natural communities. 25124934 8 20 theme DNA 1477:1479 arg1 combination 1431:1441 a combination 1429:1441 a combination of polysaccharides, extracellular DNA and amyloid protein 1429:1499 To visualize the extracellular matrix, biofilms formed by GFP-expressing cells were stained with concanavalin A, DAPI, Congo red and thioflavin T. Stains colocalized with larger cellular structures and indicated that the extracellular matrix may contain a combination of polysaccharides, extracellular DNA and amyloid protein. 25124934 5 21 theme biofilms 706:713 arg1 composition 678:688 composition 678:688 composition 678:688 Here, we investigated the development, composition and dynamics of biofilms formed by the haloarchaeon Haloferax volcanii DS2. 25124934 5 21 theme biofilms 706:713 arg1 development 665:675 development 665:675 development 665:675 Here, we investigated the development, composition and dynamics of biofilms formed by the haloarchaeon Haloferax volcanii DS2. 25124934 5 21 theme biofilms 706:713 arg1 dynamics 694:701 dynamics 694:701 dynamics 694:701 Here, we investigated the development, composition and dynamics of biofilms formed by the haloarchaeon Haloferax volcanii DS2. 25124934 14 22 contain has 2454:2456 arg1 H. 2442:2443 H. 2442:2443 H. 2442:2443 Because H. volcanii has one of the most advanced genetic systems for any archaeon, the phenotypes reported here may promote the study of genetic and developmental processes in archaeal biofilms. 25124934 14 22 contain has 2454:2456 arg2 one 2458:2460 one 2458:2460 one 2458:2460 Because H. volcanii has one of the most advanced genetic systems for any archaeon, the phenotypes reported here may promote the study of genetic and developmental processes in archaeal biofilms. 25124934 14 22 contain has 2454:2456 arg2 systems 2491:2497 the most advanced genetic systems 2465:2497 the most advanced genetic systems 2465:2497 Because H. volcanii has one of the most advanced genetic systems for any archaeon, the phenotypes reported here may promote the study of genetic and developmental processes in archaeal biofilms. 25124934 8 23 theme amyloid 1485:1491 arg1 protein 1493:1499 amyloid protein 1485:1499 amyloid protein 1485:1499 To visualize the extracellular matrix, biofilms formed by GFP-expressing cells were stained with concanavalin A, DAPI, Congo red and thioflavin T. Stains colocalized with larger cellular structures and indicated that the extracellular matrix may contain a combination of polysaccharides, extracellular DNA and amyloid protein. 25124934 7 24 theme larger 1066:1071 arg1 clusters 1073:1080 larger clusters 1066:1080 larger clusters 1066:1080 Analysis by confocal scanning laser microscopy showed that H. volcanii cells formed microcolonies within 24 h, which developed into larger clusters by 48 h and matured into flake-like towers often greater than 100 μm in height after 7 days. 25124934 9 25 theme biofilm 1524:1530 arg1 conditions 1539:1548 biofilm growth conditions 1524:1548 biofilm growth conditions 1524:1548 Following a switch to biofilm growth conditions, a sub-population of cells differentiated into chains of long rods sometimes exceeding 25 μm in length, compared to their planktonic disk-shaped morphology. 25124934 2 26 theme behaviors 433:441 arg1 differentiation 456:470 cellular differentiation 447:470 cellular differentiation during biofilm development 447:497 Advances in biofilm biology have been made over decades for model bacterial species, and include characterizations of social behaviors and cellular differentiation during biofilm development. 25124934 2 26 theme behaviors 433:441 arg1 characterizations 405:421 characterizations 405:421 characterizations of social behaviors 405:441 Advances in biofilm biology have been made over decades for model bacterial species, and include characterizations of social behaviors and cellular differentiation during biofilm development. 25124934 8 27 theme T. 1319:1320 arg1 A 1285:1285 concanavalin A 1272:1285 concanavalin A 1272:1285 To visualize the extracellular matrix, biofilms formed by GFP-expressing cells were stained with concanavalin A, DAPI, Congo red and thioflavin T. Stains colocalized with larger cellular structures and indicated that the extracellular matrix may contain a combination of polysaccharides, extracellular DNA and amyloid protein. 25124934 8 27 theme T. 1319:1320 arg1 Stains 1322:1327 Congo red and thioflavin T. Stains 1294:1327 Congo red and thioflavin T. Stains colocalized with larger cellular structures and indicated that the extracellular matrix may contain a combination of polysaccharides, extracellular DNA and amyloid protein 1294:1499 To visualize the extracellular matrix, biofilms formed by GFP-expressing cells were stained with concanavalin A, DAPI, Congo red and thioflavin T. Stains colocalized with larger cellular structures and indicated that the extracellular matrix may contain a combination of polysaccharides, extracellular DNA and amyloid protein. 25124934 0 28 theme cellular 59:66 arg1 differentiation 68:82 cellular differentiation 59:82 cellular differentiation 59:82 Biofilms formed by the archaeon Haloferax volcanii exhibit cellular differentiation and social motility, and facilitate horizontal gene transfer. 25124934 14 29 theme archaeal 2610:2617 arg1 biofilms 2619:2626 archaeal biofilms 2610:2626 archaeal biofilms 2610:2626 Because H. volcanii has one of the most advanced genetic systems for any archaeon, the phenotypes reported here may promote the study of genetic and developmental processes in archaeal biofilms. 25124934 14 30 theme processes 2597:2605 arg1 study 2562:2566 the study 2558:2566 the study of genetic and developmental processes in archaeal biofilms 2558:2626 Because H. volcanii has one of the most advanced genetic systems for any archaeon, the phenotypes reported here may promote the study of genetic and developmental processes in archaeal biofilms. 25124934 8 31 theme larger 1346:1351 arg1 structures 1362:1371 larger cellular structures 1346:1371 larger cellular structures 1346:1371 To visualize the extracellular matrix, biofilms formed by GFP-expressing cells were stained with concanavalin A, DAPI, Congo red and thioflavin T. Stains colocalized with larger cellular structures and indicated that the extracellular matrix may contain a combination of polysaccharides, extracellular DNA and amyloid protein. 25124934 8 32 theme red 1300:1302 arg1 A 1285:1285 concanavalin A 1272:1285 concanavalin A 1272:1285 To visualize the extracellular matrix, biofilms formed by GFP-expressing cells were stained with concanavalin A, DAPI, Congo red and thioflavin T. Stains colocalized with larger cellular structures and indicated that the extracellular matrix may contain a combination of polysaccharides, extracellular DNA and amyloid protein. 25124934 8 32 theme red 1300:1302 arg1 Stains 1322:1327 Congo red and thioflavin T. Stains 1294:1327 Congo red and thioflavin T. Stains colocalized with larger cellular structures and indicated that the extracellular matrix may contain a combination of polysaccharides, extracellular DNA and amyloid protein 1294:1499 To visualize the extracellular matrix, biofilms formed by GFP-expressing cells were stained with concanavalin A, DAPI, Congo red and thioflavin T. Stains colocalized with larger cellular structures and indicated that the extracellular matrix may contain a combination of polysaccharides, extracellular DNA and amyloid protein. 25124934 11 33 theme filter-based 1927:1938 arg1 method 1953:1958 a classic filter-based experimental method 1917:1958 a classic filter-based experimental method 1917:1958 Finally, we quantified gene exchange between biofilm cells, and found that it was equivalent to the mating frequency of a classic filter-based experimental method. 25124934 9 34 from μm 1640:1641 arg1 length 1646:1651 length 1646:1651 length 1646:1651 Following a switch to biofilm growth conditions, a sub-population of cells differentiated into chains of long rods sometimes exceeding 25 μm in length, compared to their planktonic disk-shaped morphology. 25124934 7 35 theme scanning 955:962 arg1 microscopy 970:979 confocal scanning laser microscopy 946:979 confocal scanning laser microscopy 946:979 Analysis by confocal scanning laser microscopy showed that H. volcanii cells formed microcolonies within 24 h, which developed into larger clusters by 48 h and matured into flake-like towers often greater than 100 μm in height after 7 days. 25124934 2 36 theme cellular 447:454 arg1 differentiation 456:470 cellular differentiation 447:470 cellular differentiation during biofilm development 447:497 Advances in biofilm biology have been made over decades for model bacterial species, and include characterizations of social behaviors and cellular differentiation during biofilm development. 25124934 14 37 from study 2562:2566 arg1 biofilms 2619:2626 archaeal biofilms 2610:2626 archaeal biofilms 2610:2626 Because H. volcanii has one of the most advanced genetic systems for any archaeon, the phenotypes reported here may promote the study of genetic and developmental processes in archaeal biofilms. 25124934 13 38 theme social 2417:2422 arg1 motility 2424:2431 social motility 2417:2431 social motility 2417:2431 H. volcanii demonstrates some biofilm phenotypes similar to bacterial biofilms, but also has interesting phenotypes that may be unique to this organism or to this class of organisms, including changes in cellular morphology and an unusual form of social motility. 25124934 10 39 theme Time-lapse 1707:1716 arg1 photography 1718:1728 Time-lapse photography 1707:1728 Time-lapse photography of static liquid biofilms 1707:1754 Time-lapse photography of static liquid biofilms also revealed wave-like social motility. 25124934 6 40 theme fluorescent 907:917 arg1 GFP 928:930 GFP 928:930 GFP 928:930 RESULTS Biofilms were cultured in static liquid and visualized with fluorescent cell membrane dyes and by engineering cells to express green fluorescent protein (GFP). 25124934 6 40 theme fluorescent 907:917 arg1 protein 919:925 green fluorescent protein 901:925 green fluorescent protein (GFP) 901:931 RESULTS Biofilms were cultured in static liquid and visualized with fluorescent cell membrane dyes and by engineering cells to express green fluorescent protein (GFP). 25124934 9 41 theme long 1607:1610 arg1 rods 1612:1615 long rods 1607:1615 long rods sometimes exceeding 25 μm in length 1607:1651 Following a switch to biofilm growth conditions, a sub-population of cells differentiated into chains of long rods sometimes exceeding 25 μm in length, compared to their planktonic disk-shaped morphology. 25124934 1 42 theme BACKGROUND 146:155 arg1 Archaea 157:163 BACKGROUND Archaea 146:163 BACKGROUND Archaea 146:163 BACKGROUND Archaea share a similar microbial lifestyle with bacteria, and not surprisingly then, also exist within matrix-enclosed communities known as biofilms. 25124934 4 43 theme archaeal 593:600 arg1 biofilms 602:609 archaeal biofilms 593:609 archaeal biofilms 593:609 However, the biology of archaeal biofilms is only now being explored. 25124934 11 44 theme method 1953:1958 arg1 frequency 1904:1912 the mating frequency 1893:1912 the mating frequency of a classic filter-based experimental method 1893:1958 Finally, we quantified gene exchange between biofilm cells, and found that it was equivalent to the mating frequency of a classic filter-based experimental method. 25124934 0 45 theme archaeon 23:30 arg1 volcanii 42:49 the archaeon Haloferax volcanii 19:49 the archaeon Haloferax volcanii 19:49 Biofilms formed by the archaeon Haloferax volcanii exhibit cellular differentiation and social motility, and facilitate horizontal gene transfer. 25124934 8 46 contain contain 1421:1427 arg2 combination 1431:1441 a combination 1429:1441 a combination of polysaccharides, extracellular DNA and amyloid protein 1429:1499 To visualize the extracellular matrix, biofilms formed by GFP-expressing cells were stained with concanavalin A, DAPI, Congo red and thioflavin T. Stains colocalized with larger cellular structures and indicated that the extracellular matrix may contain a combination of polysaccharides, extracellular DNA and amyloid protein. 25124934 8 46 contain contain 1421:1427 arg1 matrix 1410:1415 the extracellular matrix 1392:1415 the extracellular matrix 1392:1415 To visualize the extracellular matrix, biofilms formed by GFP-expressing cells were stained with concanavalin A, DAPI, Congo red and thioflavin T. Stains colocalized with larger cellular structures and indicated that the extracellular matrix may contain a combination of polysaccharides, extracellular DNA and amyloid protein. 25124934 8 47 dep Stains 1322:1327 arg1 indicated 1377:1385 indicated 1377:1385 indicated that the extracellular matrix may contain a combination of polysaccharides, extracellular DNA and amyloid protein 1377:1499 To visualize the extracellular matrix, biofilms formed by GFP-expressing cells were stained with concanavalin A, DAPI, Congo red and thioflavin T. Stains colocalized with larger cellular structures and indicated that the extracellular matrix may contain a combination of polysaccharides, extracellular DNA and amyloid protein. 25124934 8 47 dep Stains 1322:1327 arg1 colocalized 1329:1339 colocalized 1329:1339 colocalized with larger cellular structures 1329:1371 To visualize the extracellular matrix, biofilms formed by GFP-expressing cells were stained with concanavalin A, DAPI, Congo red and thioflavin T. Stains colocalized with larger cellular structures and indicated that the extracellular matrix may contain a combination of polysaccharides, extracellular DNA and amyloid protein. 25124934 13 48 from changes 2363:2369 arg1 morphology 2383:2392 cellular morphology 2374:2392 cellular morphology 2374:2392 H. volcanii demonstrates some biofilm phenotypes similar to bacterial biofilms, but also has interesting phenotypes that may be unique to this organism or to this class of organisms, including changes in cellular morphology and an unusual form of social motility. 25124934 10 49 theme liquid 1740:1745 arg1 biofilms 1747:1754 static liquid biofilms 1733:1754 static liquid biofilms 1733:1754 Time-lapse photography of static liquid biofilms also revealed wave-like social motility. 25124934 13 50 theme interesting 2263:2273 arg1 phenotypes 2275:2284 interesting phenotypes 2263:2284 interesting phenotypes that may be unique to this organism or to this class of organisms, including changes in cellular morphology and an unusual form of social motility 2263:2431 H. volcanii demonstrates some biofilm phenotypes similar to bacterial biofilms, but also has interesting phenotypes that may be unique to this organism or to this class of organisms, including changes in cellular morphology and an unusual form of social motility. 25124934 7 51 from μm 1148:1149 arg1 height 1154:1159 height 1154:1159 height 1154:1159 Analysis by confocal scanning laser microscopy showed that H. volcanii cells formed microcolonies within 24 h, which developed into larger clusters by 48 h and matured into flake-like towers often greater than 100 μm in height after 7 days. 25124934 13 52 theme motility 2424:2431 arg1 form 2409:2412 an unusual form 2398:2412 an unusual form of social motility 2398:2431 H. volcanii demonstrates some biofilm phenotypes similar to bacterial biofilms, but also has interesting phenotypes that may be unique to this organism or to this class of organisms, including changes in cellular morphology and an unusual form of social motility. 25124934 13 52 theme motility 2424:2431 arg1 changes 2363:2369 changes 2363:2369 changes in cellular morphology 2363:2392 H. volcanii demonstrates some biofilm phenotypes similar to bacterial biofilms, but also has interesting phenotypes that may be unique to this organism or to this class of organisms, including changes in cellular morphology and an unusual form of social motility. 25124934 7 53 theme confocal 946:953 arg1 microscopy 970:979 confocal scanning laser microscopy 946:979 confocal scanning laser microscopy 946:979 Analysis by confocal scanning laser microscopy showed that H. volcanii cells formed microcolonies within 24 h, which developed into larger clusters by 48 h and matured into flake-like towers often greater than 100 μm in height after 7 days. 25124934 13 54 theme bacterial 2230:2238 arg1 biofilms 2240:2247 bacterial biofilms 2230:2247 bacterial biofilms 2230:2247 H. volcanii demonstrates some biofilm phenotypes similar to bacterial biofilms, but also has interesting phenotypes that may be unique to this organism or to this class of organisms, including changes in cellular morphology and an unusual form of social motility. 25124934 13 55 theme unusual 2401:2407 arg1 form 2409:2412 an unusual form 2398:2412 an unusual form of social motility 2398:2431 H. volcanii demonstrates some biofilm phenotypes similar to bacterial biofilms, but also has interesting phenotypes that may be unique to this organism or to this class of organisms, including changes in cellular morphology and an unusual form of social motility. 25124934 8 56 theme polysaccharides 1446:1460 arg1 combination 1431:1441 a combination 1429:1441 a combination of polysaccharides, extracellular DNA and amyloid protein 1429:1499 To visualize the extracellular matrix, biofilms formed by GFP-expressing cells were stained with concanavalin A, DAPI, Congo red and thioflavin T. Stains colocalized with larger cellular structures and indicated that the extracellular matrix may contain a combination of polysaccharides, extracellular DNA and amyloid protein. 25124934 6 57 theme RESULTS 766:772 arg1 Biofilms 774:781 RESULTS Biofilms 766:781 RESULTS Biofilms 766:781 RESULTS Biofilms were cultured in static liquid and visualized with fluorescent cell membrane dyes and by engineering cells to express green fluorescent protein (GFP). 25124934 10 58 theme wave-like 1770:1778 arg1 motility 1787:1794 wave-like social motility 1770:1794 wave-like social motility 1770:1794 Time-lapse photography of static liquid biofilms also revealed wave-like social motility. 25124934 13 59 theme cellular 2374:2381 arg1 morphology 2383:2392 cellular morphology 2374:2392 cellular morphology 2374:2392 H. volcanii demonstrates some biofilm phenotypes similar to bacterial biofilms, but also has interesting phenotypes that may be unique to this organism or to this class of organisms, including changes in cellular morphology and an unusual form of social motility. 25124934 3 60 theme ecological 530:539 arg1 systems 560:566 ecological and biogeochemical systems 530:566 ecological and biogeochemical systems 530:566 Like bacteria, archaea impact ecological and biogeochemical systems. 25124934 13 61 theme biofilm 2200:2206 arg1 phenotypes 2208:2217 some biofilm phenotypes 2195:2217 some biofilm phenotypes similar to bacterial biofilms 2195:2247 H. volcanii demonstrates some biofilm phenotypes similar to bacterial biofilms, but also has interesting phenotypes that may be unique to this organism or to this class of organisms, including changes in cellular morphology and an unusual form of social motility. 25124934 7 62 theme greater 1131:1137 arg1 towers 1118:1123 flake-like towers 1107:1123 flake-like towers often greater than 100 μm in height 1107:1159 Analysis by confocal scanning laser microscopy showed that H. volcanii cells formed microcolonies within 24 h, which developed into larger clusters by 48 h and matured into flake-like towers often greater than 100 μm in height after 7 days. 25124934 6 63 theme membrane 851:858 arg1 dyes 860:863 fluorescent cell membrane dyes 834:863 fluorescent cell membrane dyes 834:863 RESULTS Biofilms were cultured in static liquid and visualized with fluorescent cell membrane dyes and by engineering cells to express green fluorescent protein (GFP). 25124934 1 64 theme matrix-enclosed 261:275 arg1 communities 277:287 matrix-enclosed communities 261:287 matrix-enclosed communities known as biofilms 261:305 BACKGROUND Archaea share a similar microbial lifestyle with bacteria, and not surprisingly then, also exist within matrix-enclosed communities known as biofilms. 25124934 12 65 theme H. 2040:2041 arg1 biofilms 2052:2059 H. volcanii biofilms 2040:2059 H. volcanii biofilms 2040:2059 CONCLUSIONS The developmental processes, functional properties and dynamics of H. volcanii biofilms provide insight on how haloarchaeal species might persist, interact and exchange DNA in natural communities. 25124934 9 66 theme planktonic 1672:1681 arg1 morphology 1695:1704 their planktonic disk-shaped morphology 1666:1704 their planktonic disk-shaped morphology 1666:1704 Following a switch to biofilm growth conditions, a sub-population of cells differentiated into chains of long rods sometimes exceeding 25 μm in length, compared to their planktonic disk-shaped morphology. 25124934 6 67 theme fluorescent 834:844 arg1 dyes 860:863 fluorescent cell membrane dyes 834:863 fluorescent cell membrane dyes 834:863 RESULTS Biofilms were cultured in static liquid and visualized with fluorescent cell membrane dyes and by engineering cells to express green fluorescent protein (GFP). 25124934 1 68 theme similar 173:179 arg1 lifestyle 191:199 a similar microbial lifestyle 171:199 a similar microbial lifestyle 171:199 BACKGROUND Archaea share a similar microbial lifestyle with bacteria, and not surprisingly then, also exist within matrix-enclosed communities known as biofilms. 25124934 12 69 theme biofilms 2052:2059 arg1 dynamics 2028:2035 dynamics 2028:2035 dynamics 2028:2035 CONCLUSIONS The developmental processes, functional properties and dynamics of H. volcanii biofilms provide insight on how haloarchaeal species might persist, interact and exchange DNA in natural communities. 25124934 12 69 theme biofilms 2052:2059 arg1 processes 1991:1999 The developmental processes 1973:1999 The developmental processes 1973:1999 CONCLUSIONS The developmental processes, functional properties and dynamics of H. volcanii biofilms provide insight on how haloarchaeal species might persist, interact and exchange DNA in natural communities. 25124934 12 69 theme biofilms 2052:2059 arg1 properties 2013:2022 functional properties 2002:2022 functional properties 2002:2022 CONCLUSIONS The developmental processes, functional properties and dynamics of H. volcanii biofilms provide insight on how haloarchaeal species might persist, interact and exchange DNA in natural communities. 25124934 14 70 theme systems 2491:2497 arg1 one 2458:2460 one 2458:2460 one 2458:2460 Because H. volcanii has one of the most advanced genetic systems for any archaeon, the phenotypes reported here may promote the study of genetic and developmental processes in archaeal biofilms. 25124934 14 70 theme systems 2491:2497 arg1 systems 2491:2497 the most advanced genetic systems 2465:2497 the most advanced genetic systems 2465:2497 Because H. volcanii has one of the most advanced genetic systems for any archaeon, the phenotypes reported here may promote the study of genetic and developmental processes in archaeal biofilms. 25124934 13 71 contain has 2259:2261 arg2 phenotypes 2275:2284 interesting phenotypes 2263:2284 interesting phenotypes that may be unique to this organism or to this class of organisms, including changes in cellular morphology and an unusual form of social motility 2263:2431 H. volcanii demonstrates some biofilm phenotypes similar to bacterial biofilms, but also has interesting phenotypes that may be unique to this organism or to this class of organisms, including changes in cellular morphology and an unusual form of social motility. 25124934 13 71 contain has 2259:2261 arg1 H. 2170:2171 H. 2170:2171 H. 2170:2171 H. volcanii demonstrates some biofilm phenotypes similar to bacterial biofilms, but also has interesting phenotypes that may be unique to this organism or to this class of organisms, including changes in cellular morphology and an unusual form of social motility. 25124934 0 72 theme gene 131:134 arg1 transfer 136:143 horizontal gene transfer 120:143 horizontal gene transfer 120:143 Biofilms formed by the archaeon Haloferax volcanii exhibit cellular differentiation and social motility, and facilitate horizontal gene transfer. 25124934 13 73 theme organisms 2342:2350 arg1 class 2333:2337 this class 2328:2337 this class of organisms, including changes in cellular morphology and an unusual form of social motility 2328:2431 H. volcanii demonstrates some biofilm phenotypes similar to bacterial biofilms, but also has interesting phenotypes that may be unique to this organism or to this class of organisms, including changes in cellular morphology and an unusual form of social motility. 25124934 2 74 theme bacterial 374:382 arg1 species 384:390 model bacterial species 368:390 model bacterial species 368:390 Advances in biofilm biology have been made over decades for model bacterial species, and include characterizations of social behaviors and cellular differentiation during biofilm development. 25124934 8 75 theme extracellular 1463:1475 arg1 DNA 1477:1479 extracellular DNA 1463:1479 extracellular DNA 1463:1479 To visualize the extracellular matrix, biofilms formed by GFP-expressing cells were stained with concanavalin A, DAPI, Congo red and thioflavin T. Stains colocalized with larger cellular structures and indicated that the extracellular matrix may contain a combination of polysaccharides, extracellular DNA and amyloid protein. 25124934 8 76 theme concanavalin 1272:1283 arg1 A 1285:1285 concanavalin A 1272:1285 concanavalin A 1272:1285 To visualize the extracellular matrix, biofilms formed by GFP-expressing cells were stained with concanavalin A, DAPI, Congo red and thioflavin T. Stains colocalized with larger cellular structures and indicated that the extracellular matrix may contain a combination of polysaccharides, extracellular DNA and amyloid protein. 25124934 8 76 theme concanavalin 1272:1283 arg1 Stains 1322:1327 Congo red and thioflavin T. Stains 1294:1327 Congo red and thioflavin T. Stains colocalized with larger cellular structures and indicated that the extracellular matrix may contain a combination of polysaccharides, extracellular DNA and amyloid protein 1294:1499 To visualize the extracellular matrix, biofilms formed by GFP-expressing cells were stained with concanavalin A, DAPI, Congo red and thioflavin T. Stains colocalized with larger cellular structures and indicated that the extracellular matrix may contain a combination of polysaccharides, extracellular DNA and amyloid protein. 25124934 8 76 theme concanavalin 1272:1283 arg1 DAPI 1288:1291 DAPI 1288:1291 DAPI 1288:1291 To visualize the extracellular matrix, biofilms formed by GFP-expressing cells were stained with concanavalin A, DAPI, Congo red and thioflavin T. Stains colocalized with larger cellular structures and indicated that the extracellular matrix may contain a combination of polysaccharides, extracellular DNA and amyloid protein. 25124934 5 77 theme Haloferax 742:750 arg1 volcanii 752:759 the haloarchaeon Haloferax volcanii 725:759 the haloarchaeon Haloferax volcanii DS2 725:763 Here, we investigated the development, composition and dynamics of biofilms formed by the haloarchaeon Haloferax volcanii DS2. 25124934 12 78 theme developmental 1977:1989 arg1 processes 1991:1999 The developmental processes 1973:1999 The developmental processes 1973:1999 CONCLUSIONS The developmental processes, functional properties and dynamics of H. volcanii biofilms provide insight on how haloarchaeal species might persist, interact and exchange DNA in natural communities. 25124934 1 79 dep surprisingly 224:235 arg1 not 220:222 not 220:222 not 220:222 BACKGROUND Archaea share a similar microbial lifestyle with bacteria, and not surprisingly then, also exist within matrix-enclosed communities known as biofilms. 25124934 8 80 theme protein 1493:1499 arg1 combination 1431:1441 a combination 1429:1441 a combination of polysaccharides, extracellular DNA and amyloid protein 1429:1499 To visualize the extracellular matrix, biofilms formed by GFP-expressing cells were stained with concanavalin A, DAPI, Congo red and thioflavin T. Stains colocalized with larger cellular structures and indicated that the extracellular matrix may contain a combination of polysaccharides, extracellular DNA and amyloid protein. 25124934 12 81 theme exchange 2133:2140 arg1 DNA 2142:2144 exchange DNA 2133:2144 exchange DNA 2133:2144 CONCLUSIONS The developmental processes, functional properties and dynamics of H. volcanii biofilms provide insight on how haloarchaeal species might persist, interact and exchange DNA in natural communities. 25124934 9 82 theme growth 1532:1537 arg1 conditions 1539:1548 biofilm growth conditions 1524:1548 biofilm growth conditions 1524:1548 Following a switch to biofilm growth conditions, a sub-population of cells differentiated into chains of long rods sometimes exceeding 25 μm in length, compared to their planktonic disk-shaped morphology. 25124934 8 83 theme thioflavin 1308:1317 arg1 A 1285:1285 concanavalin A 1272:1285 concanavalin A 1272:1285 To visualize the extracellular matrix, biofilms formed by GFP-expressing cells were stained with concanavalin A, DAPI, Congo red and thioflavin T. Stains colocalized with larger cellular structures and indicated that the extracellular matrix may contain a combination of polysaccharides, extracellular DNA and amyloid protein. 25124934 8 83 theme thioflavin 1308:1317 arg1 Stains 1322:1327 Congo red and thioflavin T. Stains 1294:1327 Congo red and thioflavin T. Stains colocalized with larger cellular structures and indicated that the extracellular matrix may contain a combination of polysaccharides, extracellular DNA and amyloid protein 1294:1499 To visualize the extracellular matrix, biofilms formed by GFP-expressing cells were stained with concanavalin A, DAPI, Congo red and thioflavin T. Stains colocalized with larger cellular structures and indicated that the extracellular matrix may contain a combination of polysaccharides, extracellular DNA and amyloid protein. 25124934 0 84 theme social 88:93 arg1 motility 95:102 social motility 88:102 social motility 88:102 Biofilms formed by the archaeon Haloferax volcanii exhibit cellular differentiation and social motility, and facilitate horizontal gene transfer. 25124934 2 85 from Advances 308:315 arg1 biology 328:334 biofilm biology 320:334 biofilm biology 320:334 Advances in biofilm biology have been made over decades for model bacterial species, and include characterizations of social behaviors and cellular differentiation during biofilm development. 25124934 0 86 theme horizontal 120:129 arg1 transfer 136:143 horizontal gene transfer 120:143 horizontal gene transfer 120:143 Biofilms formed by the archaeon Haloferax volcanii exhibit cellular differentiation and social motility, and facilitate horizontal gene transfer. 25124934 11 87 theme gene 1820:1823 arg1 exchange 1825:1832 gene exchange 1820:1832 gene exchange between biofilm cells 1820:1854 Finally, we quantified gene exchange between biofilm cells, and found that it was equivalent to the mating frequency of a classic filter-based experimental method. 25124934 14 88 theme developmental 2583:2595 arg1 processes 2597:2605 genetic and developmental processes 2571:2605 genetic and developmental processes 2571:2605 Because H. volcanii has one of the most advanced genetic systems for any archaeon, the phenotypes reported here may promote the study of genetic and developmental processes in archaeal biofilms. 25124934 13 89 from form 2409:2412 arg1 morphology 2383:2392 cellular morphology 2374:2392 cellular morphology 2374:2392 H. volcanii demonstrates some biofilm phenotypes similar to bacterial biofilms, but also has interesting phenotypes that may be unique to this organism or to this class of organisms, including changes in cellular morphology and an unusual form of social motility. 25124934 7 90 theme H. 993:994 arg1 cells 1005:1009 H. volcanii cells 993:1009 H. volcanii cells 993:1009 Analysis by confocal scanning laser microscopy showed that H. volcanii cells formed microcolonies within 24 h, which developed into larger clusters by 48 h and matured into flake-like towers often greater than 100 μm in height after 7 days. 25124934 9 91 theme cells 1571:1575 arg1 sub-population 1553:1566 a sub-population 1551:1566 a sub-population of cells 1551:1575 Following a switch to biofilm growth conditions, a sub-population of cells differentiated into chains of long rods sometimes exceeding 25 μm in length, compared to their planktonic disk-shaped morphology. 25124934 8 92 theme cellular 1353:1360 arg1 structures 1362:1371 larger cellular structures 1346:1371 larger cellular structures 1346:1371 To visualize the extracellular matrix, biofilms formed by GFP-expressing cells were stained with concanavalin A, DAPI, Congo red and thioflavin T. Stains colocalized with larger cellular structures and indicated that the extracellular matrix may contain a combination of polysaccharides, extracellular DNA and amyloid protein. 25124934 11 93 theme experimental 1940:1951 arg1 method 1953:1958 a classic filter-based experimental method 1917:1958 a classic filter-based experimental method 1917:1958 Finally, we quantified gene exchange between biofilm cells, and found that it was equivalent to the mating frequency of a classic filter-based experimental method. 25124934 11 94 theme classic 1919:1925 arg1 method 1953:1958 a classic filter-based experimental method 1917:1958 a classic filter-based experimental method 1917:1958 Finally, we quantified gene exchange between biofilm cells, and found that it was equivalent to the mating frequency of a classic filter-based experimental method. 25124934 7 95 theme laser 964:968 arg1 microscopy 970:979 confocal scanning laser microscopy 946:979 confocal scanning laser microscopy 946:979 Analysis by confocal scanning laser microscopy showed that H. volcanii cells formed microcolonies within 24 h, which developed into larger clusters by 48 h and matured into flake-like towers often greater than 100 μm in height after 7 days. 25124934 4 96 theme biofilms 602:609 arg1 biology 582:588 the biology 578:588 the biology of archaeal biofilms 578:609 However, the biology of archaeal biofilms is only now being explored. 25124934 2 97 theme social 426:431 arg1 behaviors 433:441 social behaviors 426:441 social behaviors 426:441 Advances in biofilm biology have been made over decades for model bacterial species, and include characterizations of social behaviors and cellular differentiation during biofilm development. 25124934 0 98 theme Haloferax 32:40 arg1 volcanii 42:49 the archaeon Haloferax volcanii 19:49 the archaeon Haloferax volcanii 19:49 Biofilms formed by the archaeon Haloferax volcanii exhibit cellular differentiation and social motility, and facilitate horizontal gene transfer. 25124934 6 99 theme green 901:905 arg1 GFP 928:930 GFP 928:930 GFP 928:930 RESULTS Biofilms were cultured in static liquid and visualized with fluorescent cell membrane dyes and by engineering cells to express green fluorescent protein (GFP). 25124934 6 99 theme green 901:905 arg1 protein 919:925 green fluorescent protein 901:925 green fluorescent protein (GFP) 901:931 RESULTS Biofilms were cultured in static liquid and visualized with fluorescent cell membrane dyes and by engineering cells to express green fluorescent protein (GFP). 25124934 9 100 theme rods 1612:1615 arg1 chains 1597:1602 chains 1597:1602 chains of long rods sometimes exceeding 25 μm in length 1597:1651 Following a switch to biofilm growth conditions, a sub-population of cells differentiated into chains of long rods sometimes exceeding 25 μm in length, compared to their planktonic disk-shaped morphology. 25124934 5 101 dep development 665:675 arg1 the 661:663 the 661:663 the 661:663 Here, we investigated the development, composition and dynamics of biofilms formed by the haloarchaeon Haloferax volcanii DS2. 25124934 8 102 theme extracellular 1396:1408 arg1 matrix 1410:1415 the extracellular matrix 1392:1415 the extracellular matrix 1392:1415 To visualize the extracellular matrix, biofilms formed by GFP-expressing cells were stained with concanavalin A, DAPI, Congo red and thioflavin T. Stains colocalized with larger cellular structures and indicated that the extracellular matrix may contain a combination of polysaccharides, extracellular DNA and amyloid protein. 25124934 14 103 theme advanced 2474:2481 arg1 systems 2491:2497 the most advanced genetic systems 2465:2497 the most advanced genetic systems 2465:2497 Because H. volcanii has one of the most advanced genetic systems for any archaeon, the phenotypes reported here may promote the study of genetic and developmental processes in archaeal biofilms. 25124934 2 104 theme biofilm 479:485 arg1 development 487:497 biofilm development 479:497 biofilm development 479:497 Advances in biofilm biology have been made over decades for model bacterial species, and include characterizations of social behaviors and cellular differentiation during biofilm development. 25124934 10 105 theme static 1733:1738 arg1 biofilms 1747:1754 static liquid biofilms 1733:1754 static liquid biofilms 1733:1754 Time-lapse photography of static liquid biofilms also revealed wave-like social motility. 25124934 13 106 theme similar 2219:2225 arg1 phenotypes 2208:2217 some biofilm phenotypes 2195:2217 some biofilm phenotypes similar to bacterial biofilms 2195:2247 H. volcanii demonstrates some biofilm phenotypes similar to bacterial biofilms, but also has interesting phenotypes that may be unique to this organism or to this class of organisms, including changes in cellular morphology and an unusual form of social motility. 25124934 8 107 theme GFP-expressing 1233:1246 arg1 cells 1248:1252 GFP-expressing cells 1233:1252 GFP-expressing cells 1233:1252 To visualize the extracellular matrix, biofilms formed by GFP-expressing cells were stained with concanavalin A, DAPI, Congo red and thioflavin T. Stains colocalized with larger cellular structures and indicated that the extracellular matrix may contain a combination of polysaccharides, extracellular DNA and amyloid protein. 25124934 2 108 theme model 368:372 arg1 species 384:390 model bacterial species 368:390 model bacterial species 368:390 Advances in biofilm biology have been made over decades for model bacterial species, and include characterizations of social behaviors and cellular differentiation during biofilm development. 28588567 0 0 theme Cupriavidus 81:91 arg1 JMP134 101:106 Cupriavidus necator JMP134 81:106 Cupriavidus necator JMP134 81:106 Biofilm vs. Planktonic Lifestyle: Consequences for Pesticide 2,4-D Metabolism by Cupriavidus necator JMP134. 28588567 11 1 theme planktonic 1754:1763 arg1 counterparts 1765:1776 their planktonic counterparts 1748:1776 their planktonic counterparts 1748:1776 These results suggest that sessile bacteria differ more in their anabolism than in their catabolism compared to their planktonic counterparts. 28588567 6 2 attach attached 993:1000 arg1 grains 1014:1019 the sand grains 1005:1019 the sand grains 1005:1019 After only 3 days, approximately 80% of the cells were attached to the sand grains and microscopy images showed that the porous medium was totally clogged by the development of a biofilm. 28588567 6 2 attach attached 993:1000 arg2 cells 982:986 the cells 978:986 the cells 978:986 After only 3 days, approximately 80% of the cells were attached to the sand grains and microscopy images showed that the porous medium was totally clogged by the development of a biofilm. 28588567 6 2 attach attached 993:1000 arg2 % 973:973 approximately 80% 957:973 approximately 80% of the cells 957:986 After only 3 days, approximately 80% of the cells were attached to the sand grains and microscopy images showed that the porous medium was totally clogged by the development of a biofilm. 28588567 2 3 theme biofilm 364:370 arg1 formation 372:380 biofilm formation 364:380 biofilm formation 364:380 The present study focuses on the influence of biofilm formation on the metabolism of a pesticide, 2,4-dichlorophenoxyacetic acid (2,4-D), by Cupriavidus necator JMP134. 28588567 6 4 theme biofilm 1117:1123 arg1 development 1100:1110 the development 1096:1110 the development of a biofilm 1096:1123 After only 3 days, approximately 80% of the cells were attached to the sand grains and microscopy images showed that the porous medium was totally clogged by the development of a biofilm. 28588567 8 5 from mineralization 1274:1287 arg1 matrix 1368:1373 the biofilm matrix 1356:1373 the biofilm matrix 1356:1373 This difference was due to (1) a higher (+8%) mineralization of 2,4-D by sessile bacteria and (2) a retention (15%) of 2,4-D in the biofilm matrix. 28588567 12 6 from dynamics 1907:1914 arg1 media 1926:1930 porous media 1919:1930 porous media 1919:1930 This study stresses the importance of considering interactions between microorganisms and their habitat when studying pollutant dynamics in porous media. 28588567 1 7 from environments 158:169 arg1 development 113:123 The development 109:123 The development of bacterial biofilms in natural environments 109:169 The development of bacterial biofilms in natural environments may alter important functions, such as pollutant bioremediation by modifying both the degraders' physiology and/or interactions within the matrix. 28588567 10 8 theme isotopic 1543:1550 arg1 signature 1552:1560 the FAME isotopic signature 1534:1560 the FAME isotopic signature 1534:1560 Compound-specific isotope analysis revealed that the FAME isotopic signature was less affected by the biofilm lifestyle than was the FAME composition. 28588567 8 9 theme 2,4-D 1347:1351 arg1 mineralization 1274:1287 a higher (+8%) mineralization 1259:1287 (1) a higher (+8%) mineralization of 2,4-D by sessile bacteria 1255:1316 This difference was due to (1) a higher (+8%) mineralization of 2,4-D by sessile bacteria and (2) a retention (15%) of 2,4-D in the biofilm matrix. 28588567 8 9 theme 2,4-D 1347:1351 arg1 retention 1328:1336 a retention 1326:1336 (2) a retention (15%) of 2,4-D in the biofilm matrix 1322:1373 This difference was due to (1) a higher (+8%) mineralization of 2,4-D by sessile bacteria and (2) a retention (15%) of 2,4-D in the biofilm matrix. 28588567 8 9 theme 2,4-D 1347:1351 arg1 % 1341:1341 15% 1339:1341 15% 1339:1341 This difference was due to (1) a higher (+8%) mineralization of 2,4-D by sessile bacteria and (2) a retention (15%) of 2,4-D in the biofilm matrix. 28588567 7 10 from solution 1173:1180 arg1 2,4-D 1160:1164 2,4-D 1160:1164 2,4-D 1160:1164 After 10 days, there was 25% less 2,4-D in the solution in samples with sand than in control samples. 28588567 4 11 theme surface 755:761 arg1 colonization 763:774 the surface colonization 751:774 the surface colonization by electron microscopy 751:797 Bacterial numbers and 2,4-D concentrations in solution were followed by spectrophotometry, the respiration rate by gas chromatography and the surface colonization by electron microscopy. 28588567 0 12 theme necator 93:99 arg1 JMP134 101:106 Cupriavidus necator JMP134 81:106 Cupriavidus necator JMP134 81:106 Biofilm vs. Planktonic Lifestyle: Consequences for Pesticide 2,4-D Metabolism by Cupriavidus necator JMP134. 28588567 8 13 theme biofilm 1360:1366 arg1 matrix 1368:1373 the biofilm matrix 1356:1373 the biofilm matrix 1356:1373 This difference was due to (1) a higher (+8%) mineralization of 2,4-D by sessile bacteria and (2) a retention (15%) of 2,4-D in the biofilm matrix. 28588567 7 14 with samples 1185:1191 arg1 sand 1198:1201 sand 1198:1201 sand 1198:1201 After 10 days, there was 25% less 2,4-D in the solution in samples with sand than in control samples. 28588567 2 15 from influence 351:359 arg1 metabolism 389:398 the metabolism 385:398 the metabolism of a pesticide, 2,4-dichlorophenoxyacetic acid (2,4-D), by Cupriavidus necator JMP134 385:484 The present study focuses on the influence of biofilm formation on the metabolism of a pesticide, 2,4-dichlorophenoxyacetic acid (2,4-D), by Cupriavidus necator JMP134. 28588567 6 16 theme porous 1059:1064 arg1 medium 1066:1071 the porous medium 1055:1071 the porous medium 1055:1071 After only 3 days, approximately 80% of the cells were attached to the sand grains and microscopy images showed that the porous medium was totally clogged by the development of a biofilm. 28588567 3 17 theme Pure 487:490 arg1 cultures 492:499 Pure cultures 487:499 Pure cultures 487:499 Pure cultures were established in a liquid medium with 2,4-D as a sole carbon source with or without sand grains for 10 days. 28588567 3 17 theme Pure 487:490 arg1 source 565:570 a sole carbon source 551:570 a sole carbon source 551:570 Pure cultures were established in a liquid medium with 2,4-D as a sole carbon source with or without sand grains for 10 days. 28588567 4 18 theme gas 728:730 arg1 chromatography 732:745 gas chromatography 728:745 gas chromatography 728:745 Bacterial numbers and 2,4-D concentrations in solution were followed by spectrophotometry, the respiration rate by gas chromatography and the surface colonization by electron microscopy. 28588567 10 19 theme Compound-specific 1485:1501 arg1 analysis 1511:1518 Compound-specific isotope analysis 1485:1518 Compound-specific isotope analysis 1485:1518 Compound-specific isotope analysis revealed that the FAME isotopic signature was less affected by the biofilm lifestyle than was the FAME composition. 28588567 5 20 theme Methyl 857:862 arg1 Ester 864:868 Fatty Acid Methyl Ester 846:868 Fatty Acid Methyl Ester (FAME) 846:875 In addition, isotopic techniques coupled with Fatty Acid Methyl Ester (FAME) profiling were used to determine possible metabolic changes. 28588567 5 20 theme Methyl 857:862 arg1 FAME 871:874 FAME 871:874 FAME 871:874 In addition, isotopic techniques coupled with Fatty Acid Methyl Ester (FAME) profiling were used to determine possible metabolic changes. 28588567 8 21 from retention 1328:1336 arg1 matrix 1368:1373 the biofilm matrix 1356:1373 the biofilm matrix 1356:1373 This difference was due to (1) a higher (+8%) mineralization of 2,4-D by sessile bacteria and (2) a retention (15%) of 2,4-D in the biofilm matrix. 28588567 10 22 theme biofilm 1587:1593 arg1 lifestyle 1595:1603 the biofilm lifestyle 1583:1603 the biofilm lifestyle 1583:1603 Compound-specific isotope analysis revealed that the FAME isotopic signature was less affected by the biofilm lifestyle than was the FAME composition. 28588567 4 23 from concentrations 641:654 arg1 solution 659:666 solution 659:666 solution 659:666 Bacterial numbers and 2,4-D concentrations in solution were followed by spectrophotometry, the respiration rate by gas chromatography and the surface colonization by electron microscopy. 28588567 1 24 theme important 181:189 arg1 functions 191:199 important functions 181:199 important functions 181:199 The development of bacterial biofilms in natural environments may alter important functions, such as pollutant bioremediation by modifying both the degraders' physiology and/or interactions within the matrix. 28588567 3 25 theme liquid 523:528 arg1 medium 530:535 a liquid medium 521:535 a liquid medium with 2,4-D 521:546 Pure cultures were established in a liquid medium with 2,4-D as a sole carbon source with or without sand grains for 10 days. 28588567 7 26 theme control 1211:1217 arg1 samples 1219:1225 control samples 1211:1225 control samples 1211:1225 After 10 days, there was 25% less 2,4-D in the solution in samples with sand than in control samples. 28588567 1 27 from biofilms 138:145 arg1 environments 158:169 natural environments 150:169 natural environments 150:169 The development of bacterial biofilms in natural environments may alter important functions, such as pollutant bioremediation by modifying both the degraders' physiology and/or interactions within the matrix. 28588567 3 28 theme carbon 558:563 arg1 cultures 492:499 Pure cultures 487:499 Pure cultures 487:499 Pure cultures were established in a liquid medium with 2,4-D as a sole carbon source with or without sand grains for 10 days. 28588567 3 28 theme carbon 558:563 arg1 source 565:570 a sole carbon source 551:570 a sole carbon source 551:570 Pure cultures were established in a liquid medium with 2,4-D as a sole carbon source with or without sand grains for 10 days. 28588567 4 29 theme respiration 708:718 arg1 rate 720:723 the respiration rate 704:723 the respiration rate by gas chromatography 704:745 Bacterial numbers and 2,4-D concentrations in solution were followed by spectrophotometry, the respiration rate by gas chromatography and the surface colonization by electron microscopy. 28588567 1 30 from development 113:123 arg1 environments 158:169 natural environments 150:169 natural environments 150:169 The development of bacterial biofilms in natural environments may alter important functions, such as pollutant bioremediation by modifying both the degraders' physiology and/or interactions within the matrix. 28588567 2 31 theme present 322:328 arg1 study 330:334 The present study 318:334 The present study 318:334 The present study focuses on the influence of biofilm formation on the metabolism of a pesticide, 2,4-dichlorophenoxyacetic acid (2,4-D), by Cupriavidus necator JMP134. 28588567 6 32 theme microscopy 1025:1034 arg1 images 1036:1041 microscopy images 1025:1041 microscopy images 1025:1041 After only 3 days, approximately 80% of the cells were attached to the sand grains and microscopy images showed that the porous medium was totally clogged by the development of a biofilm. 28588567 5 33 theme isotopic 813:820 arg1 techniques 822:831 isotopic techniques 813:831 isotopic techniques coupled with Fatty Acid Methyl Ester (FAME) 813:875 In addition, isotopic techniques coupled with Fatty Acid Methyl Ester (FAME) profiling were used to determine possible metabolic changes. 28588567 8 34 dep mineralization 1274:1287 arg1 1 1256:1256 1 1256:1256 1 1256:1256 This difference was due to (1) a higher (+8%) mineralization of 2,4-D by sessile bacteria and (2) a retention (15%) of 2,4-D in the biofilm matrix. 28588567 5 35 theme metabolic 919:927 arg1 changes 929:935 possible metabolic changes 910:935 possible metabolic changes 910:935 In addition, isotopic techniques coupled with Fatty Acid Methyl Ester (FAME) profiling were used to determine possible metabolic changes. 28588567 6 36 theme sand 1009:1012 arg1 grains 1014:1019 the sand grains 1005:1019 the sand grains 1005:1019 After only 3 days, approximately 80% of the cells were attached to the sand grains and microscopy images showed that the porous medium was totally clogged by the development of a biofilm. 28588567 4 37 from numbers 623:629 arg1 solution 659:666 solution 659:666 solution 659:666 Bacterial numbers and 2,4-D concentrations in solution were followed by spectrophotometry, the respiration rate by gas chromatography and the surface colonization by electron microscopy. 28588567 4 38 theme Bacterial 613:621 arg1 numbers 623:629 Bacterial numbers 613:629 Bacterial numbers 613:629 Bacterial numbers and 2,4-D concentrations in solution were followed by spectrophotometry, the respiration rate by gas chromatography and the surface colonization by electron microscopy. 28588567 0 39 theme Planktonic 12:21 arg1 Lifestyle 23:31 Planktonic Lifestyle 12:31 Planktonic Lifestyle 12:31 Biofilm vs. Planktonic Lifestyle: Consequences for Pesticide 2,4-D Metabolism by Cupriavidus necator JMP134. 28588567 3 40 theme sole 553:556 arg1 cultures 492:499 Pure cultures 487:499 Pure cultures 487:499 Pure cultures were established in a liquid medium with 2,4-D as a sole carbon source with or without sand grains for 10 days. 28588567 3 40 theme sole 553:556 arg1 source 565:570 a sole carbon source 551:570 a sole carbon source 551:570 Pure cultures were established in a liquid medium with 2,4-D as a sole carbon source with or without sand grains for 10 days. 28588567 2 41 theme 2,4-dichlorophenoxyacetic 416:440 arg1 2,4-D 448:452 2,4-D 448:452 2,4-D 448:452 The present study focuses on the influence of biofilm formation on the metabolism of a pesticide, 2,4-dichlorophenoxyacetic acid (2,4-D), by Cupriavidus necator JMP134. 28588567 2 41 theme 2,4-dichlorophenoxyacetic 416:440 arg1 pesticide 405:413 a pesticide 403:413 a pesticide 403:413 The present study focuses on the influence of biofilm formation on the metabolism of a pesticide, 2,4-dichlorophenoxyacetic acid (2,4-D), by Cupriavidus necator JMP134. 28588567 2 41 theme 2,4-dichlorophenoxyacetic 416:440 arg1 acid 442:445 2,4-dichlorophenoxyacetic acid 416:445 2,4-dichlorophenoxyacetic acid (2,4-D) 416:453 The present study focuses on the influence of biofilm formation on the metabolism of a pesticide, 2,4-dichlorophenoxyacetic acid (2,4-D), by Cupriavidus necator JMP134. 28588567 3 42 with medium 530:535 arg1 2,4-D 542:546 2,4-D 542:546 2,4-D 542:546 Pure cultures were established in a liquid medium with 2,4-D as a sole carbon source with or without sand grains for 10 days. 28588567 8 43 dep retention 1328:1336 arg1 2 1323:1323 2 1323:1323 2 1323:1323 This difference was due to (1) a higher (+8%) mineralization of 2,4-D by sessile bacteria and (2) a retention (15%) of 2,4-D in the biofilm matrix. 28588567 7 44 dep 2,4-D 1160:1164 arg1 % 1153:1153 25% 1151:1153 25% 1151:1153 After 10 days, there was 25% less 2,4-D in the solution in samples with sand than in control samples. 28588567 5 45 theme Fatty 846:850 arg1 Ester 864:868 Fatty Acid Methyl Ester 846:868 Fatty Acid Methyl Ester (FAME) 846:875 In addition, isotopic techniques coupled with Fatty Acid Methyl Ester (FAME) profiling were used to determine possible metabolic changes. 28588567 5 45 theme Fatty 846:850 arg1 FAME 871:874 FAME 871:874 FAME 871:874 In addition, isotopic techniques coupled with Fatty Acid Methyl Ester (FAME) profiling were used to determine possible metabolic changes. 28588567 5 46 used used 892:895 arg2 techniques 822:831 isotopic techniques 813:831 isotopic techniques coupled with Fatty Acid Methyl Ester (FAME) 813:875 In addition, isotopic techniques coupled with Fatty Acid Methyl Ester (FAME) profiling were used to determine possible metabolic changes. 28588567 8 47 dep higher 1261:1266 arg1 % 1271:1271 +8% 1269:1271 +8% 1269:1271 This difference was due to (1) a higher (+8%) mineralization of 2,4-D by sessile bacteria and (2) a retention (15%) of 2,4-D in the biofilm matrix. 28588567 1 48 theme pollutant 210:218 arg1 bioremediation 220:233 pollutant bioremediation 210:233 pollutant bioremediation 210:233 The development of bacterial biofilms in natural environments may alter important functions, such as pollutant bioremediation by modifying both the degraders' physiology and/or interactions within the matrix. 28588567 2 49 theme necator 471:477 arg1 JMP134 479:484 Cupriavidus necator JMP134 459:484 Cupriavidus necator JMP134 459:484 The present study focuses on the influence of biofilm formation on the metabolism of a pesticide, 2,4-dichlorophenoxyacetic acid (2,4-D), by Cupriavidus necator JMP134. 28588567 3 50 theme sand 588:591 arg1 grains 593:598 sand grains 588:598 sand grains for 10 days 588:610 Pure cultures were established in a liquid medium with 2,4-D as a sole carbon source with or without sand grains for 10 days. 28588567 2 51 theme pesticide 405:413 arg1 metabolism 389:398 the metabolism 385:398 the metabolism of a pesticide, 2,4-dichlorophenoxyacetic acid (2,4-D), by Cupriavidus necator JMP134 385:484 The present study focuses on the influence of biofilm formation on the metabolism of a pesticide, 2,4-dichlorophenoxyacetic acid (2,4-D), by Cupriavidus necator JMP134. 28588567 2 52 theme Cupriavidus 459:469 arg1 JMP134 479:484 Cupriavidus necator JMP134 459:484 Cupriavidus necator JMP134 459:484 The present study focuses on the influence of biofilm formation on the metabolism of a pesticide, 2,4-dichlorophenoxyacetic acid (2,4-D), by Cupriavidus necator JMP134. 28588567 0 53 theme 2,4-D 61:65 arg1 Metabolism 67:76 Pesticide 2,4-D Metabolism 51:76 Pesticide 2,4-D Metabolism by Cupriavidus necator JMP134 51:106 Biofilm vs. Planktonic Lifestyle: Consequences for Pesticide 2,4-D Metabolism by Cupriavidus necator JMP134. 28588567 8 54 theme 2,4-D 1292:1296 arg1 mineralization 1274:1287 a higher (+8%) mineralization 1259:1287 (1) a higher (+8%) mineralization of 2,4-D by sessile bacteria 1255:1316 This difference was due to (1) a higher (+8%) mineralization of 2,4-D by sessile bacteria and (2) a retention (15%) of 2,4-D in the biofilm matrix. 28588567 8 54 theme 2,4-D 1292:1296 arg1 retention 1328:1336 a retention 1326:1336 (2) a retention (15%) of 2,4-D in the biofilm matrix 1322:1373 This difference was due to (1) a higher (+8%) mineralization of 2,4-D by sessile bacteria and (2) a retention (15%) of 2,4-D in the biofilm matrix. 28588567 8 54 theme 2,4-D 1292:1296 arg1 % 1341:1341 15% 1339:1341 15% 1339:1341 This difference was due to (1) a higher (+8%) mineralization of 2,4-D by sessile bacteria and (2) a retention (15%) of 2,4-D in the biofilm matrix. 28588567 8 55 theme higher 1261:1266 arg1 mineralization 1274:1287 a higher (+8%) mineralization 1259:1287 (1) a higher (+8%) mineralization of 2,4-D by sessile bacteria 1255:1316 This difference was due to (1) a higher (+8%) mineralization of 2,4-D by sessile bacteria and (2) a retention (15%) of 2,4-D in the biofilm matrix. 28588567 12 56 theme pollutant 1897:1905 arg1 dynamics 1907:1914 pollutant dynamics 1897:1914 pollutant dynamics in porous media 1897:1930 This study stresses the importance of considering interactions between microorganisms and their habitat when studying pollutant dynamics in porous media. 28588567 10 57 dep composition 1623:1633 arg1 than 1605:1608 than 1605:1608 than 1605:1608 Compound-specific isotope analysis revealed that the FAME isotopic signature was less affected by the biofilm lifestyle than was the FAME composition. 28588567 10 57 dep composition 1623:1633 arg1 was 1610:1612 was 1610:1612 was 1610:1612 Compound-specific isotope analysis revealed that the FAME isotopic signature was less affected by the biofilm lifestyle than was the FAME composition. 28588567 1 58 theme natural 150:156 arg1 environments 158:169 natural environments 150:169 natural environments 150:169 The development of bacterial biofilms in natural environments may alter important functions, such as pollutant bioremediation by modifying both the degraders' physiology and/or interactions within the matrix. 28588567 9 59 theme carbohydrates 1399:1411 arg1 carbohydrates 1399:1411 carbohydrates 1399:1411 carbohydrates 1399:1411 Besides, the amount of carbohydrates, presumably constituting the biofilm polysaccharides, increased by 63%. 28588567 9 59 theme carbohydrates 1399:1411 arg1 amount 1389:1394 the amount 1385:1394 the amount of carbohydrates, presumably constituting the biofilm polysaccharides, 1385:1465 Besides, the amount of carbohydrates, presumably constituting the biofilm polysaccharides, increased by 63%. 28588567 10 60 theme FAME 1618:1621 arg1 composition 1623:1633 the FAME composition 1614:1633 the FAME composition 1614:1633 Compound-specific isotope analysis revealed that the FAME isotopic signature was less affected by the biofilm lifestyle than was the FAME composition. 28588567 9 61 theme biofilm 1442:1448 arg1 polysaccharides 1450:1464 the biofilm polysaccharides 1438:1464 the biofilm polysaccharides 1438:1464 Besides, the amount of carbohydrates, presumably constituting the biofilm polysaccharides, increased by 63%. 28588567 8 62 theme sessile 1301:1307 arg1 bacteria 1309:1316 sessile bacteria 1301:1316 sessile bacteria 1301:1316 This difference was due to (1) a higher (+8%) mineralization of 2,4-D by sessile bacteria and (2) a retention (15%) of 2,4-D in the biofilm matrix. 28588567 1 63 theme bacterial 128:136 arg1 biofilms 138:145 bacterial biofilms 128:145 bacterial biofilms in natural environments 128:169 The development of bacterial biofilms in natural environments may alter important functions, such as pollutant bioremediation by modifying both the degraders' physiology and/or interactions within the matrix. 28588567 10 64 theme FAME 1538:1541 arg1 signature 1552:1560 the FAME isotopic signature 1534:1560 the FAME isotopic signature 1534:1560 Compound-specific isotope analysis revealed that the FAME isotopic signature was less affected by the biofilm lifestyle than was the FAME composition. 28588567 7 65 from 2,4-D 1160:1164 arg1 solution 1173:1180 the solution 1169:1180 the solution 1169:1180 After 10 days, there was 25% less 2,4-D in the solution in samples with sand than in control samples. 28588567 4 66 theme electron 779:786 arg1 microscopy 788:797 electron microscopy 779:797 electron microscopy 779:797 Bacterial numbers and 2,4-D concentrations in solution were followed by spectrophotometry, the respiration rate by gas chromatography and the surface colonization by electron microscopy. 28588567 1 67 theme biofilms 138:145 arg1 development 113:123 The development 109:123 The development of bacterial biofilms in natural environments 109:169 The development of bacterial biofilms in natural environments may alter important functions, such as pollutant bioremediation by modifying both the degraders' physiology and/or interactions within the matrix. 28588567 11 68 theme sessile 1663:1669 arg1 bacteria 1671:1678 sessile bacteria 1663:1678 sessile bacteria 1663:1678 These results suggest that sessile bacteria differ more in their anabolism than in their catabolism compared to their planktonic counterparts. 28588567 5 69 theme possible 910:917 arg1 changes 929:935 possible metabolic changes 910:935 possible metabolic changes 910:935 In addition, isotopic techniques coupled with Fatty Acid Methyl Ester (FAME) profiling were used to determine possible metabolic changes. 28588567 5 70 theme Acid 852:855 arg1 Ester 864:868 Fatty Acid Methyl Ester 846:868 Fatty Acid Methyl Ester (FAME) 846:875 In addition, isotopic techniques coupled with Fatty Acid Methyl Ester (FAME) profiling were used to determine possible metabolic changes. 28588567 5 70 theme Acid 852:855 arg1 FAME 871:874 FAME 871:874 FAME 871:874 In addition, isotopic techniques coupled with Fatty Acid Methyl Ester (FAME) profiling were used to determine possible metabolic changes. 28588567 1 71 dep such 202:205 arg1 as 207:208 as 207:208 as 207:208 The development of bacterial biofilms in natural environments may alter important functions, such as pollutant bioremediation by modifying both the degraders' physiology and/or interactions within the matrix. 28588567 12 72 theme porous 1919:1924 arg1 media 1926:1930 porous media 1919:1930 porous media 1919:1930 This study stresses the importance of considering interactions between microorganisms and their habitat when studying pollutant dynamics in porous media. 28588567 4 73 theme 2,4-D 635:639 arg1 concentrations 641:654 2,4-D concentrations 635:654 2,4-D concentrations in solution 635:666 Bacterial numbers and 2,4-D concentrations in solution were followed by spectrophotometry, the respiration rate by gas chromatography and the surface colonization by electron microscopy. 28588567 10 74 theme isotope 1503:1509 arg1 analysis 1511:1518 Compound-specific isotope analysis 1485:1518 Compound-specific isotope analysis 1485:1518 Compound-specific isotope analysis revealed that the FAME isotopic signature was less affected by the biofilm lifestyle than was the FAME composition. 28588567 0 75 theme Pesticide 51:59 arg1 Metabolism 67:76 Pesticide 2,4-D Metabolism 51:76 Pesticide 2,4-D Metabolism by Cupriavidus necator JMP134 51:106 Biofilm vs. Planktonic Lifestyle: Consequences for Pesticide 2,4-D Metabolism by Cupriavidus necator JMP134. 28588567 0 76 dep Biofilm 0:6 arg1 Consequences 34:45 Consequences 34:45 Biofilm vs. Planktonic Lifestyle: Consequences for Pesticide 2,4-D Metabolism by Cupriavidus necator JMP134. 0:107 Biofilm vs. Planktonic Lifestyle: Consequences for Pesticide 2,4-D Metabolism by Cupriavidus necator JMP134. 28588567 2 77 theme formation 372:380 arg1 influence 351:359 the influence 347:359 the influence of biofilm formation on the metabolism of a pesticide, 2,4-dichlorophenoxyacetic acid (2,4-D), by Cupriavidus necator JMP134 347:484 The present study focuses on the influence of biofilm formation on the metabolism of a pesticide, 2,4-dichlorophenoxyacetic acid (2,4-D), by Cupriavidus necator JMP134. 28588567 6 78 theme cells 982:986 arg1 % 973:973 approximately 80% 957:973 approximately 80% of the cells 957:986 After only 3 days, approximately 80% of the cells were attached to the sand grains and microscopy images showed that the porous medium was totally clogged by the development of a biofilm. 28588567 6 78 theme cells 982:986 arg1 cells 982:986 the cells 978:986 the cells 978:986 After only 3 days, approximately 80% of the cells were attached to the sand grains and microscopy images showed that the porous medium was totally clogged by the development of a biofilm. 27692038 4 0 theme pH 510:511 arg1 values 513:518 pH values 510:518 pH values 510:518 Growth occurred aerobically from 15 to 55 °C (optimum, 40 °C) and at pH values from 4.5 to 7.0 (optimum, 6.5). 27692038 11 1 theme capsulatum 1281:1290 arg1 neighbour 1255:1263 its nearest cultured phylogenetic neighbour 1221:1263 its nearest cultured phylogenetic neighbour 1221:1263 A comparative genome analysis revealed an average nucleotide identity of 72.2 % between PMMR2T and its nearest cultured phylogenetic neighbour, Acidobacterium capsulatum ATCC 51196T (=JCM 7670T); analysis of the 16S rRNA gene revealed a 96.8 % sequence identity with Acidobacterium capsulatum ATCC 51196T. 27692038 11 1 theme capsulatum 1281:1290 arg1 51196T 1297:1302 Acidobacterium capsulatum ATCC 51196T 1266:1302 Acidobacterium capsulatum ATCC 51196T (=JCM 7670T) 1266:1315 A comparative genome analysis revealed an average nucleotide identity of 72.2 % between PMMR2T and its nearest cultured phylogenetic neighbour, Acidobacterium capsulatum ATCC 51196T (=JCM 7670T); analysis of the 16S rRNA gene revealed a 96.8 % sequence identity with Acidobacterium capsulatum ATCC 51196T. 27692038 11 1 theme capsulatum 1281:1290 arg1 7670T 1310:1314 =JCM 7670T 1305:1314 =JCM 7670T 1305:1314 A comparative genome analysis revealed an average nucleotide identity of 72.2 % between PMMR2T and its nearest cultured phylogenetic neighbour, Acidobacterium capsulatum ATCC 51196T (=JCM 7670T); analysis of the 16S rRNA gene revealed a 96.8 % sequence identity with Acidobacterium capsulatum ATCC 51196T. 27692038 6 2 theme carbon 715:720 arg1 polysaccharides 676:690 various polysaccharides 668:690 various polysaccharides 668:690 However, results of a genomic analysis suggested that various polysaccharides might be hydrolysed as carbon sources, and evidence for pectin degradation was observed in liquid cultures. 27692038 6 2 theme carbon 715:720 arg1 sources 722:728 carbon sources 715:728 carbon sources 715:728 However, results of a genomic analysis suggested that various polysaccharides might be hydrolysed as carbon sources, and evidence for pectin degradation was observed in liquid cultures. 27692038 11 3 theme ATCC 1415:1418 arg1 51196T 1420:1425 Acidobacterium capsulatum ATCC 51196T 1389:1425 Acidobacterium capsulatum ATCC 51196T 1389:1425 A comparative genome analysis revealed an average nucleotide identity of 72.2 % between PMMR2T and its nearest cultured phylogenetic neighbour, Acidobacterium capsulatum ATCC 51196T (=JCM 7670T); analysis of the 16S rRNA gene revealed a 96.8 % sequence identity with Acidobacterium capsulatum ATCC 51196T. 27692038 2 4 theme dead 264:267 arg1 trunk 274:278 a geothermally heated dead tree trunk 242:278 a geothermally heated dead tree trunk in Hawai'i Volcanoes National Park (HI, USA) 242:323 A novel member of Acidobacteria was isolated from a microbial mat growing on a geothermally heated dead tree trunk in Hawai'i Volcanoes National Park (HI, USA). 27692038 10 5 theme 57.2mol 1112:1118 arg1 content 1100:1106 The G+C content 1092:1106 The G+C content 1092:1106 The G+C content was 57.2mol%. 27692038 10 5 theme 57.2mol 1112:1118 arg1 % 1119:1119 57.2mol% 1112:1119 57.2mol% 1112:1119 The G+C content was 57.2mol%. 27692038 6 6 theme liquid 783:788 arg1 cultures 790:797 liquid cultures 783:797 liquid cultures 783:797 However, results of a genomic analysis suggested that various polysaccharides might be hydrolysed as carbon sources, and evidence for pectin degradation was observed in liquid cultures. 27692038 11 7 dep cultured 1233:1240 arg1 nearest 1225:1231 nearest 1225:1231 nearest 1225:1231 A comparative genome analysis revealed an average nucleotide identity of 72.2 % between PMMR2T and its nearest cultured phylogenetic neighbour, Acidobacterium capsulatum ATCC 51196T (=JCM 7670T); analysis of the 16S rRNA gene revealed a 96.8 % sequence identity with Acidobacterium capsulatum ATCC 51196T. 27692038 6 8 located observed 771:778 arg1 cultures 790:797 liquid cultures 783:797 liquid cultures 783:797 However, results of a genomic analysis suggested that various polysaccharides might be hydrolysed as carbon sources, and evidence for pectin degradation was observed in liquid cultures. 27692038 6 8 located observed 771:778 arg2 evidence 735:742 evidence 735:742 evidence for pectin degradation 735:765 However, results of a genomic analysis suggested that various polysaccharides might be hydrolysed as carbon sources, and evidence for pectin degradation was observed in liquid cultures. 27692038 6 9 theme various 668:674 arg1 polysaccharides 676:690 various polysaccharides 668:690 various polysaccharides 668:690 However, results of a genomic analysis suggested that various polysaccharides might be hydrolysed as carbon sources, and evidence for pectin degradation was observed in liquid cultures. 27692038 6 9 theme various 668:674 arg1 sources 722:728 carbon sources 715:728 carbon sources 715:728 However, results of a genomic analysis suggested that various polysaccharides might be hydrolysed as carbon sources, and evidence for pectin degradation was observed in liquid cultures. 27692038 7 10 theme sub-atmospheric 954:968 arg1 concentrations 970:983 sub-atmospheric concentrations 954:983 sub-atmospheric concentrations 954:983 A genomic analysis also revealed genes for a Group 1f uptake hydrogenase; assays with liquid cultures confirmed hydrogen consumption, including uptake at sub-atmospheric concentrations. 27692038 11 11 theme phylogenetic 1242:1253 arg1 51196T 1297:1302 Acidobacterium capsulatum ATCC 51196T 1266:1302 Acidobacterium capsulatum ATCC 51196T (=JCM 7670T) 1266:1315 A comparative genome analysis revealed an average nucleotide identity of 72.2 % between PMMR2T and its nearest cultured phylogenetic neighbour, Acidobacterium capsulatum ATCC 51196T (=JCM 7670T); analysis of the 16S rRNA gene revealed a 96.8 % sequence identity with Acidobacterium capsulatum ATCC 51196T. 27692038 11 11 theme phylogenetic 1242:1253 arg1 neighbour 1255:1263 its nearest cultured phylogenetic neighbour 1221:1263 its nearest cultured phylogenetic neighbour 1221:1263 A comparative genome analysis revealed an average nucleotide identity of 72.2 % between PMMR2T and its nearest cultured phylogenetic neighbour, Acidobacterium capsulatum ATCC 51196T (=JCM 7670T); analysis of the 16S rRNA gene revealed a 96.8 % sequence identity with Acidobacterium capsulatum ATCC 51196T. 27692038 5 12 theme sugars 571:576 arg1 range 562:566 A limited range 552:566 A limited range of sugars and organic acids 552:594 A limited range of sugars and organic acids supported growth. 27692038 7 13 theme liquid 886:891 arg1 cultures 893:900 liquid cultures 886:900 liquid cultures 886:900 A genomic analysis also revealed genes for a Group 1f uptake hydrogenase; assays with liquid cultures confirmed hydrogen consumption, including uptake at sub-atmospheric concentrations. 27692038 1 14 dep nov. 61:64 arg1 mat 160:162 a geothermally heated Hawaiian microbial mat 119:162 a geothermally heated Hawaiian microbial mat 119:162 nov., a novel member of Acidobacteria subdivision 1, from a geothermally heated Hawaiian microbial mat. 27692038 11 15 theme sequence 1366:1373 arg1 identity 1375:1382 a 96.8 % sequence identity 1357:1382 a 96.8 % sequence identity with Acidobacterium capsulatum ATCC 51196T 1357:1425 A comparative genome analysis revealed an average nucleotide identity of 72.2 % between PMMR2T and its nearest cultured phylogenetic neighbour, Acidobacterium capsulatum ATCC 51196T (=JCM 7670T); analysis of the 16S rRNA gene revealed a 96.8 % sequence identity with Acidobacterium capsulatum ATCC 51196T. 27692038 5 16 theme organic 582:588 arg1 acids 590:594 organic acids 582:594 organic acids 582:594 A limited range of sugars and organic acids supported growth. 27692038 14 17 theme genus 1711:1715 arg1 Acidobacterium 1717:1730 the genus Acidobacterium 1707:1730 the genus Acidobacterium 1707:1730 The type strain, PMMR2T (=DSM 27394T=LMG 28340T), is the second formal addition to the genus Acidobacterium. 27692038 11 18 theme 96.8  1359:1363 arg1 % 1364:1364 % 1364:1364 % 1364:1364 A comparative genome analysis revealed an average nucleotide identity of 72.2 % between PMMR2T and its nearest cultured phylogenetic neighbour, Acidobacterium capsulatum ATCC 51196T (=JCM 7670T); analysis of the 16S rRNA gene revealed a 96.8 % sequence identity with Acidobacterium capsulatum ATCC 51196T. 27692038 4 19 dep optimum 487:493 arg1 40 °C 496:500 40 °C 496:500 40 °C 496:500 Growth occurred aerobically from 15 to 55 °C (optimum, 40 °C) and at pH values from 4.5 to 7.0 (optimum, 6.5). 27692038 1 20 theme heated 134:139 arg1 mat 160:162 a geothermally heated Hawaiian microbial mat 119:162 a geothermally heated Hawaiian microbial mat 119:162 nov., a novel member of Acidobacteria subdivision 1, from a geothermally heated Hawaiian microbial mat. 27692038 12 21 theme name 1574:1577 arg1 sp 1602:1603 the name Acidobacterium ailaaui sp 1570:1603 the name Acidobacterium ailaaui sp 1570:1603 These results and other phenotypic differences indicated that strain PMMR2T represents a novel species in the genus Acidobacterium, for which the name Acidobacterium ailaaui sp. 27692038 12 22 theme other 1446:1450 arg1 differences 1463:1473 other phenotypic differences 1446:1473 other phenotypic differences 1446:1473 These results and other phenotypic differences indicated that strain PMMR2T represents a novel species in the genus Acidobacterium, for which the name Acidobacterium ailaaui sp. 27692038 11 23 theme nucleotide 1172:1181 arg1 identity 1183:1190 an average nucleotide identity 1161:1190 an average nucleotide identity of 72.2 % between PMMR2T and its nearest cultured phylogenetic neighbour, Acidobacterium capsulatum ATCC 51196T (=JCM 7670T) 1161:1315 A comparative genome analysis revealed an average nucleotide identity of 72.2 % between PMMR2T and its nearest cultured phylogenetic neighbour, Acidobacterium capsulatum ATCC 51196T (=JCM 7670T); analysis of the 16S rRNA gene revealed a 96.8 % sequence identity with Acidobacterium capsulatum ATCC 51196T. 27692038 11 24 theme capsulatum 1404:1413 arg1 51196T 1420:1425 Acidobacterium capsulatum ATCC 51196T 1389:1425 Acidobacterium capsulatum ATCC 51196T 1389:1425 A comparative genome analysis revealed an average nucleotide identity of 72.2 % between PMMR2T and its nearest cultured phylogenetic neighbour, Acidobacterium capsulatum ATCC 51196T (=JCM 7670T); analysis of the 16S rRNA gene revealed a 96.8 % sequence identity with Acidobacterium capsulatum ATCC 51196T. 27692038 4 25 dep 55 °C 480:484 arg1 to 477:478 to 477:478 to 477:478 Growth occurred aerobically from 15 to 55 °C (optimum, 40 °C) and at pH values from 4.5 to 7.0 (optimum, 6.5). 27692038 7 26 theme 1f 851:852 arg1 hydrogenase 861:871 a Group 1f uptake hydrogenase 843:871 a Group 1f uptake hydrogenase 843:871 A genomic analysis also revealed genes for a Group 1f uptake hydrogenase; assays with liquid cultures confirmed hydrogen consumption, including uptake at sub-atmospheric concentrations. 27692038 1 27 theme microbial 150:158 arg1 mat 160:162 a geothermally heated Hawaiian microbial mat 119:162 a geothermally heated Hawaiian microbial mat 119:162 nov., a novel member of Acidobacteria subdivision 1, from a geothermally heated Hawaiian microbial mat. 27692038 12 28 theme ailaaui 1594:1600 arg1 sp 1602:1603 the name Acidobacterium ailaaui sp 1570:1603 the name Acidobacterium ailaaui sp 1570:1603 These results and other phenotypic differences indicated that strain PMMR2T represents a novel species in the genus Acidobacterium, for which the name Acidobacterium ailaaui sp. 27692038 12 29 theme genus 1538:1542 arg1 Acidobacterium 1544:1557 the genus Acidobacterium 1534:1557 the genus Acidobacterium 1534:1557 These results and other phenotypic differences indicated that strain PMMR2T represents a novel species in the genus Acidobacterium, for which the name Acidobacterium ailaaui sp. 27692038 11 30 theme % 1200:1200 arg1 identity 1183:1190 an average nucleotide identity 1161:1190 an average nucleotide identity of 72.2 % between PMMR2T and its nearest cultured phylogenetic neighbour, Acidobacterium capsulatum ATCC 51196T (=JCM 7670T) 1161:1315 A comparative genome analysis revealed an average nucleotide identity of 72.2 % between PMMR2T and its nearest cultured phylogenetic neighbour, Acidobacterium capsulatum ATCC 51196T (=JCM 7670T); analysis of the 16S rRNA gene revealed a 96.8 % sequence identity with Acidobacterium capsulatum ATCC 51196T. 27692038 3 31 theme PMMR2T 383:388 arg1 non-motile 395:404 non-motile 395:404 non-motile 395:404 The rod-shaped, Gram-negative capsulated cells of strain PMMR2T were non-motile and catalase and oxidase negative. 27692038 3 31 theme PMMR2T 383:388 arg1 cells 367:371 The rod-shaped, Gram-negative capsulated cells 326:371 The rod-shaped, Gram-negative capsulated cells of strain PMMR2T 326:388 The rod-shaped, Gram-negative capsulated cells of strain PMMR2T were non-motile and catalase and oxidase negative. 27692038 1 32 theme novel 69:73 arg1 nov. 61:64 nov. 61:64 nov. 61:64 nov., a novel member of Acidobacteria subdivision 1, from a geothermally heated Hawaiian microbial mat. 27692038 1 32 theme novel 69:73 arg1 member 75:80 a novel member 67:80 a novel member of Acidobacteria subdivision 1 67:111 nov., a novel member of Acidobacteria subdivision 1, from a geothermally heated Hawaiian microbial mat. 27692038 2 33 dep Volcanoes 291:299 arg1 HI 316:317 HI 316:317 HI 316:317 A novel member of Acidobacteria was isolated from a microbial mat growing on a geothermally heated dead tree trunk in Hawai'i Volcanoes National Park (HI, USA). 27692038 2 33 dep Volcanoes 291:299 arg1 Park 310:313 Park 310:313 Park 310:313 A novel member of Acidobacteria was isolated from a microbial mat growing on a geothermally heated dead tree trunk in Hawai'i Volcanoes National Park (HI, USA). 27692038 2 33 dep Volcanoes 291:299 arg1 USA 320:322 USA 320:322 USA 320:322 A novel member of Acidobacteria was isolated from a microbial mat growing on a geothermally heated dead tree trunk in Hawai'i Volcanoes National Park (HI, USA). 27692038 14 34 theme second 1681:1686 arg1 addition 1695:1702 the second formal addition 1677:1702 the second formal addition to the genus Acidobacterium 1677:1730 The type strain, PMMR2T (=DSM 27394T=LMG 28340T), is the second formal addition to the genus Acidobacterium. 27692038 14 34 theme second 1681:1686 arg1 strain 1633:1638 The type strain 1624:1638 The type strain 1624:1638 The type strain, PMMR2T (=DSM 27394T=LMG 28340T), is the second formal addition to the genus Acidobacterium. 27692038 9 35 theme Major 1027:1031 arg1 acids 1048:1052 Major membrane fatty acids 1027:1052 Major membrane fatty acids 1027:1052 Major membrane fatty acids included iso-C15 : 0 and iso-C17 : 0. 27692038 1 36 theme subdivision 99:109 arg1 nov. 61:64 nov. 61:64 nov. 61:64 nov., a novel member of Acidobacteria subdivision 1, from a geothermally heated Hawaiian microbial mat. 27692038 1 36 theme subdivision 99:109 arg1 member 75:80 a novel member 67:80 a novel member of Acidobacteria subdivision 1 67:111 nov., a novel member of Acidobacteria subdivision 1, from a geothermally heated Hawaiian microbial mat. 27692038 9 37 dep iso-C15  1063:1070 arg1  0 1088:1089  0 1088:1089 iso-C15 : 0 and iso-C17 : 0 1063:1089 Major membrane fatty acids included iso-C15 : 0 and iso-C17 : 0. 27692038 9 37 dep iso-C15  1063:1070 arg1 iso-C17  1079:1086 iso-C17  1079:1086 iso-C17  1079:1086 Major membrane fatty acids included iso-C15 : 0 and iso-C17 : 0. 27692038 9 37 dep iso-C15  1063:1070 arg1  0 1072:1073  0 1072:1073  0 1072:1073 Major membrane fatty acids included iso-C15 : 0 and iso-C17 : 0. 27692038 3 38 theme capsulated 356:365 arg1 non-motile 395:404 non-motile 395:404 non-motile 395:404 The rod-shaped, Gram-negative capsulated cells of strain PMMR2T were non-motile and catalase and oxidase negative. 27692038 3 38 theme capsulated 356:365 arg1 cells 367:371 The rod-shaped, Gram-negative capsulated cells 326:371 The rod-shaped, Gram-negative capsulated cells of strain PMMR2T 326:388 The rod-shaped, Gram-negative capsulated cells of strain PMMR2T were non-motile and catalase and oxidase negative. 27692038 11 39 theme rRNA 1338:1341 arg1 gene 1343:1346 the 16S rRNA gene 1330:1346 the 16S rRNA gene 1330:1346 A comparative genome analysis revealed an average nucleotide identity of 72.2 % between PMMR2T and its nearest cultured phylogenetic neighbour, Acidobacterium capsulatum ATCC 51196T (=JCM 7670T); analysis of the 16S rRNA gene revealed a 96.8 % sequence identity with Acidobacterium capsulatum ATCC 51196T. 27692038 0 40 theme Acidobacterium 34:47 arg1 sp 57:58 Acidobacterium ailaaui sp 34:58 Acidobacterium ailaaui sp 34:58 Isolation and characterization of Acidobacterium ailaaui sp. 27692038 6 41 theme pectin 748:753 arg1 degradation 755:765 pectin degradation 748:765 pectin degradation 748:765 However, results of a genomic analysis suggested that various polysaccharides might be hydrolysed as carbon sources, and evidence for pectin degradation was observed in liquid cultures. 27692038 7 42 with assays 874:879 arg1 cultures 893:900 liquid cultures 886:900 liquid cultures 886:900 A genomic analysis also revealed genes for a Group 1f uptake hydrogenase; assays with liquid cultures confirmed hydrogen consumption, including uptake at sub-atmospheric concentrations. 27692038 6 43 theme analysis 644:651 arg1 results 623:629 results 623:629 results of a genomic analysis 623:651 However, results of a genomic analysis suggested that various polysaccharides might be hydrolysed as carbon sources, and evidence for pectin degradation was observed in liquid cultures. 27692038 0 44 theme sp 57:58 arg1 characterization 14:29 characterization 14:29 characterization 14:29 Isolation and characterization of Acidobacterium ailaaui sp. 27692038 0 44 theme sp 57:58 arg1 Isolation 0:8 Isolation 0:8 Isolation 0:8 Isolation and characterization of Acidobacterium ailaaui sp. 27692038 14 45 theme 27394T=LMG 1654:1663 arg1 28340T 1665:1670 =DSM 27394T=LMG 28340T 1649:1670 =DSM 27394T=LMG 28340T 1649:1670 The type strain, PMMR2T (=DSM 27394T=LMG 28340T), is the second formal addition to the genus Acidobacterium. 27692038 14 45 theme 27394T=LMG 1654:1663 arg1 PMMR2T 1641:1646 PMMR2T 1641:1646 PMMR2T (=DSM 27394T=LMG 28340T) 1641:1671 The type strain, PMMR2T (=DSM 27394T=LMG 28340T), is the second formal addition to the genus Acidobacterium. 27692038 4 46 dep optimum 537:543 arg1 6.5 546:548 6.5 546:548 6.5 546:548 Growth occurred aerobically from 15 to 55 °C (optimum, 40 °C) and at pH values from 4.5 to 7.0 (optimum, 6.5). 27692038 11 47 theme comparative 1124:1134 arg1 analysis 1143:1150 A comparative genome analysis 1122:1150 A comparative genome analysis 1122:1150 A comparative genome analysis revealed an average nucleotide identity of 72.2 % between PMMR2T and its nearest cultured phylogenetic neighbour, Acidobacterium capsulatum ATCC 51196T (=JCM 7670T); analysis of the 16S rRNA gene revealed a 96.8 % sequence identity with Acidobacterium capsulatum ATCC 51196T. 27692038 2 48 theme Acidobacteria 183:195 arg1 member 173:178 A novel member 165:178 A novel member of Acidobacteria 165:195 A novel member of Acidobacteria was isolated from a microbial mat growing on a geothermally heated dead tree trunk in Hawai'i Volcanoes National Park (HI, USA). 27692038 11 49 theme ATCC 1292:1295 arg1 neighbour 1255:1263 its nearest cultured phylogenetic neighbour 1221:1263 its nearest cultured phylogenetic neighbour 1221:1263 A comparative genome analysis revealed an average nucleotide identity of 72.2 % between PMMR2T and its nearest cultured phylogenetic neighbour, Acidobacterium capsulatum ATCC 51196T (=JCM 7670T); analysis of the 16S rRNA gene revealed a 96.8 % sequence identity with Acidobacterium capsulatum ATCC 51196T. 27692038 11 49 theme ATCC 1292:1295 arg1 51196T 1297:1302 Acidobacterium capsulatum ATCC 51196T 1266:1302 Acidobacterium capsulatum ATCC 51196T (=JCM 7670T) 1266:1315 A comparative genome analysis revealed an average nucleotide identity of 72.2 % between PMMR2T and its nearest cultured phylogenetic neighbour, Acidobacterium capsulatum ATCC 51196T (=JCM 7670T); analysis of the 16S rRNA gene revealed a 96.8 % sequence identity with Acidobacterium capsulatum ATCC 51196T. 27692038 11 49 theme ATCC 1292:1295 arg1 7670T 1310:1314 =JCM 7670T 1305:1314 =JCM 7670T 1305:1314 A comparative genome analysis revealed an average nucleotide identity of 72.2 % between PMMR2T and its nearest cultured phylogenetic neighbour, Acidobacterium capsulatum ATCC 51196T (=JCM 7670T); analysis of the 16S rRNA gene revealed a 96.8 % sequence identity with Acidobacterium capsulatum ATCC 51196T. 27692038 11 50 theme Acidobacterium 1266:1279 arg1 neighbour 1255:1263 its nearest cultured phylogenetic neighbour 1221:1263 its nearest cultured phylogenetic neighbour 1221:1263 A comparative genome analysis revealed an average nucleotide identity of 72.2 % between PMMR2T and its nearest cultured phylogenetic neighbour, Acidobacterium capsulatum ATCC 51196T (=JCM 7670T); analysis of the 16S rRNA gene revealed a 96.8 % sequence identity with Acidobacterium capsulatum ATCC 51196T. 27692038 11 50 theme Acidobacterium 1266:1279 arg1 51196T 1297:1302 Acidobacterium capsulatum ATCC 51196T 1266:1302 Acidobacterium capsulatum ATCC 51196T (=JCM 7670T) 1266:1315 A comparative genome analysis revealed an average nucleotide identity of 72.2 % between PMMR2T and its nearest cultured phylogenetic neighbour, Acidobacterium capsulatum ATCC 51196T (=JCM 7670T); analysis of the 16S rRNA gene revealed a 96.8 % sequence identity with Acidobacterium capsulatum ATCC 51196T. 27692038 11 50 theme Acidobacterium 1266:1279 arg1 7670T 1310:1314 =JCM 7670T 1305:1314 =JCM 7670T 1305:1314 A comparative genome analysis revealed an average nucleotide identity of 72.2 % between PMMR2T and its nearest cultured phylogenetic neighbour, Acidobacterium capsulatum ATCC 51196T (=JCM 7670T); analysis of the 16S rRNA gene revealed a 96.8 % sequence identity with Acidobacterium capsulatum ATCC 51196T. 27692038 14 51 theme type 1628:1631 arg1 PMMR2T 1641:1646 PMMR2T 1641:1646 PMMR2T (=DSM 27394T=LMG 28340T) 1641:1671 The type strain, PMMR2T (=DSM 27394T=LMG 28340T), is the second formal addition to the genus Acidobacterium. 27692038 14 51 theme type 1628:1631 arg1 addition 1695:1702 the second formal addition 1677:1702 the second formal addition to the genus Acidobacterium 1677:1730 The type strain, PMMR2T (=DSM 27394T=LMG 28340T), is the second formal addition to the genus Acidobacterium. 27692038 14 51 theme type 1628:1631 arg1 strain 1633:1638 The type strain 1624:1638 The type strain 1624:1638 The type strain, PMMR2T (=DSM 27394T=LMG 28340T), is the second formal addition to the genus Acidobacterium. 27692038 5 52 theme limited 554:560 arg1 range 562:566 A limited range 552:566 A limited range of sugars and organic acids 552:594 A limited range of sugars and organic acids supported growth. 27692038 2 53 theme tree 269:272 arg1 trunk 274:278 a geothermally heated dead tree trunk 242:278 a geothermally heated dead tree trunk in Hawai'i Volcanoes National Park (HI, USA) 242:323 A novel member of Acidobacteria was isolated from a microbial mat growing on a geothermally heated dead tree trunk in Hawai'i Volcanoes National Park (HI, USA). 27692038 10 54 theme G+C 1096:1098 arg1 content 1100:1106 The G+C content 1092:1106 The G+C content 1092:1106 The G+C content was 57.2mol%. 27692038 10 54 theme G+C 1096:1098 arg1 % 1119:1119 57.2mol% 1112:1119 57.2mol% 1112:1119 The G+C content was 57.2mol%. 27692038 9 55 theme fatty 1042:1046 arg1 acids 1048:1052 Major membrane fatty acids 1027:1052 Major membrane fatty acids 1027:1052 Major membrane fatty acids included iso-C15 : 0 and iso-C17 : 0. 27692038 2 56 theme heated 257:262 arg1 trunk 274:278 a geothermally heated dead tree trunk 242:278 a geothermally heated dead tree trunk in Hawai'i Volcanoes National Park (HI, USA) 242:323 A novel member of Acidobacteria was isolated from a microbial mat growing on a geothermally heated dead tree trunk in Hawai'i Volcanoes National Park (HI, USA). 27692038 5 57 theme acids 590:594 arg1 range 562:566 A limited range 552:566 A limited range of sugars and organic acids 552:594 A limited range of sugars and organic acids supported growth. 27692038 12 58 theme novel 1517:1521 arg1 species 1523:1529 a novel species 1515:1529 a novel species 1515:1529 These results and other phenotypic differences indicated that strain PMMR2T represents a novel species in the genus Acidobacterium, for which the name Acidobacterium ailaaui sp. 27692038 12 59 from species 1523:1529 arg1 Acidobacterium 1544:1557 the genus Acidobacterium 1534:1557 the genus Acidobacterium 1534:1557 These results and other phenotypic differences indicated that strain PMMR2T represents a novel species in the genus Acidobacterium, for which the name Acidobacterium ailaaui sp. 27692038 2 60 theme microbial 217:225 arg1 mat 227:229 a microbial mat 215:229 a microbial mat growing on a geothermally heated dead tree trunk in Hawai'i Volcanoes National Park (HI, USA) 215:323 A novel member of Acidobacteria was isolated from a microbial mat growing on a geothermally heated dead tree trunk in Hawai'i Volcanoes National Park (HI, USA). 27692038 14 61 theme =DSM 1649:1652 arg1 28340T 1665:1670 =DSM 27394T=LMG 28340T 1649:1670 =DSM 27394T=LMG 28340T 1649:1670 The type strain, PMMR2T (=DSM 27394T=LMG 28340T), is the second formal addition to the genus Acidobacterium. 27692038 14 61 theme =DSM 1649:1652 arg1 PMMR2T 1641:1646 PMMR2T 1641:1646 PMMR2T (=DSM 27394T=LMG 28340T) 1641:1671 The type strain, PMMR2T (=DSM 27394T=LMG 28340T), is the second formal addition to the genus Acidobacterium. 27692038 11 62 theme cultured 1233:1240 arg1 51196T 1297:1302 Acidobacterium capsulatum ATCC 51196T 1266:1302 Acidobacterium capsulatum ATCC 51196T (=JCM 7670T) 1266:1315 A comparative genome analysis revealed an average nucleotide identity of 72.2 % between PMMR2T and its nearest cultured phylogenetic neighbour, Acidobacterium capsulatum ATCC 51196T (=JCM 7670T); analysis of the 16S rRNA gene revealed a 96.8 % sequence identity with Acidobacterium capsulatum ATCC 51196T. 27692038 11 62 theme cultured 1233:1240 arg1 neighbour 1255:1263 its nearest cultured phylogenetic neighbour 1221:1263 its nearest cultured phylogenetic neighbour 1221:1263 A comparative genome analysis revealed an average nucleotide identity of 72.2 % between PMMR2T and its nearest cultured phylogenetic neighbour, Acidobacterium capsulatum ATCC 51196T (=JCM 7670T); analysis of the 16S rRNA gene revealed a 96.8 % sequence identity with Acidobacterium capsulatum ATCC 51196T. 27692038 7 63 theme hydrogen 912:919 arg1 consumption 921:931 hydrogen consumption 912:931 hydrogen consumption 912:931 A genomic analysis also revealed genes for a Group 1f uptake hydrogenase; assays with liquid cultures confirmed hydrogen consumption, including uptake at sub-atmospheric concentrations. 27692038 12 64 theme strain 1490:1495 arg1 PMMR2T 1497:1502 strain PMMR2T 1490:1502 strain PMMR2T 1490:1502 These results and other phenotypic differences indicated that strain PMMR2T represents a novel species in the genus Acidobacterium, for which the name Acidobacterium ailaaui sp. 27692038 11 65 theme % 1364:1364 arg1 identity 1375:1382 a 96.8 % sequence identity 1357:1382 a 96.8 % sequence identity with Acidobacterium capsulatum ATCC 51196T 1357:1425 A comparative genome analysis revealed an average nucleotide identity of 72.2 % between PMMR2T and its nearest cultured phylogenetic neighbour, Acidobacterium capsulatum ATCC 51196T (=JCM 7670T); analysis of the 16S rRNA gene revealed a 96.8 % sequence identity with Acidobacterium capsulatum ATCC 51196T. 27692038 4 66 dep 7.0 532:534 arg1 to 529:530 to 529:530 to 529:530 Growth occurred aerobically from 15 to 55 °C (optimum, 40 °C) and at pH values from 4.5 to 7.0 (optimum, 6.5). 27692038 14 67 theme formal 1688:1693 arg1 addition 1695:1702 the second formal addition 1677:1702 the second formal addition to the genus Acidobacterium 1677:1730 The type strain, PMMR2T (=DSM 27394T=LMG 28340T), is the second formal addition to the genus Acidobacterium. 27692038 14 67 theme formal 1688:1693 arg1 strain 1633:1638 The type strain 1624:1638 The type strain 1624:1638 The type strain, PMMR2T (=DSM 27394T=LMG 28340T), is the second formal addition to the genus Acidobacterium. 27692038 12 68 theme phenotypic 1452:1461 arg1 differences 1463:1473 other phenotypic differences 1446:1473 other phenotypic differences 1446:1473 These results and other phenotypic differences indicated that strain PMMR2T represents a novel species in the genus Acidobacterium, for which the name Acidobacterium ailaaui sp. 27692038 11 69 with identity 1375:1382 arg1 51196T 1420:1425 Acidobacterium capsulatum ATCC 51196T 1389:1425 Acidobacterium capsulatum ATCC 51196T 1389:1425 A comparative genome analysis revealed an average nucleotide identity of 72.2 % between PMMR2T and its nearest cultured phylogenetic neighbour, Acidobacterium capsulatum ATCC 51196T (=JCM 7670T); analysis of the 16S rRNA gene revealed a 96.8 % sequence identity with Acidobacterium capsulatum ATCC 51196T. 27692038 11 70 theme Acidobacterium 1389:1402 arg1 51196T 1420:1425 Acidobacterium capsulatum ATCC 51196T 1389:1425 Acidobacterium capsulatum ATCC 51196T 1389:1425 A comparative genome analysis revealed an average nucleotide identity of 72.2 % between PMMR2T and its nearest cultured phylogenetic neighbour, Acidobacterium capsulatum ATCC 51196T (=JCM 7670T); analysis of the 16S rRNA gene revealed a 96.8 % sequence identity with Acidobacterium capsulatum ATCC 51196T. 27692038 1 71 theme Hawaiian 141:148 arg1 mat 160:162 a geothermally heated Hawaiian microbial mat 119:162 a geothermally heated Hawaiian microbial mat 119:162 nov., a novel member of Acidobacteria subdivision 1, from a geothermally heated Hawaiian microbial mat. 27692038 11 72 theme average 1164:1170 arg1 identity 1183:1190 an average nucleotide identity 1161:1190 an average nucleotide identity of 72.2 % between PMMR2T and its nearest cultured phylogenetic neighbour, Acidobacterium capsulatum ATCC 51196T (=JCM 7670T) 1161:1315 A comparative genome analysis revealed an average nucleotide identity of 72.2 % between PMMR2T and its nearest cultured phylogenetic neighbour, Acidobacterium capsulatum ATCC 51196T (=JCM 7670T); analysis of the 16S rRNA gene revealed a 96.8 % sequence identity with Acidobacterium capsulatum ATCC 51196T. 27692038 7 73 theme uptake 854:859 arg1 hydrogenase 861:871 a Group 1f uptake hydrogenase 843:871 a Group 1f uptake hydrogenase 843:871 A genomic analysis also revealed genes for a Group 1f uptake hydrogenase; assays with liquid cultures confirmed hydrogen consumption, including uptake at sub-atmospheric concentrations. 27692038 12 74 theme Acidobacterium 1579:1592 arg1 sp 1602:1603 the name Acidobacterium ailaaui sp 1570:1603 the name Acidobacterium ailaaui sp 1570:1603 These results and other phenotypic differences indicated that strain PMMR2T represents a novel species in the genus Acidobacterium, for which the name Acidobacterium ailaaui sp. 27692038 2 75 attach isolated 201:208 arg2 member 173:178 A novel member 165:178 A novel member of Acidobacteria 165:195 A novel member of Acidobacteria was isolated from a microbial mat growing on a geothermally heated dead tree trunk in Hawai'i Volcanoes National Park (HI, USA). 27692038 2 75 attach isolated 201:208 arg1 mat 227:229 a microbial mat 215:229 a microbial mat growing on a geothermally heated dead tree trunk in Hawai'i Volcanoes National Park (HI, USA) 215:323 A novel member of Acidobacteria was isolated from a microbial mat growing on a geothermally heated dead tree trunk in Hawai'i Volcanoes National Park (HI, USA). 27692038 3 76 dep rod-shaped 330:339 arg1 Gram-negative 342:354 Gram-negative 342:354 Gram-negative 342:354 The rod-shaped, Gram-negative capsulated cells of strain PMMR2T were non-motile and catalase and oxidase negative. 27692038 7 77 theme Group 845:849 arg1 hydrogenase 861:871 a Group 1f uptake hydrogenase 843:871 a Group 1f uptake hydrogenase 843:871 A genomic analysis also revealed genes for a Group 1f uptake hydrogenase; assays with liquid cultures confirmed hydrogen consumption, including uptake at sub-atmospheric concentrations. 27692038 3 78 theme rod-shaped 330:339 arg1 non-motile 395:404 non-motile 395:404 non-motile 395:404 The rod-shaped, Gram-negative capsulated cells of strain PMMR2T were non-motile and catalase and oxidase negative. 27692038 3 78 theme rod-shaped 330:339 arg1 cells 367:371 The rod-shaped, Gram-negative capsulated cells 326:371 The rod-shaped, Gram-negative capsulated cells of strain PMMR2T 326:388 The rod-shaped, Gram-negative capsulated cells of strain PMMR2T were non-motile and catalase and oxidase negative. 27692038 11 79 theme gene 1343:1346 arg1 analysis 1318:1325 analysis 1318:1325 analysis of the 16S rRNA gene 1318:1346 A comparative genome analysis revealed an average nucleotide identity of 72.2 % between PMMR2T and its nearest cultured phylogenetic neighbour, Acidobacterium capsulatum ATCC 51196T (=JCM 7670T); analysis of the 16S rRNA gene revealed a 96.8 % sequence identity with Acidobacterium capsulatum ATCC 51196T. 27692038 3 80 theme strain 376:381 arg1 PMMR2T 383:388 strain PMMR2T 376:388 strain PMMR2T 376:388 The rod-shaped, Gram-negative capsulated cells of strain PMMR2T were non-motile and catalase and oxidase negative. 27692038 1 81 theme Acidobacteria 85:97 arg1 subdivision 99:109 Acidobacteria subdivision 1 85:111 Acidobacteria subdivision 1 85:111 nov., a novel member of Acidobacteria subdivision 1, from a geothermally heated Hawaiian microbial mat. 27692038 2 82 theme novel 167:171 arg1 member 173:178 A novel member 165:178 A novel member of Acidobacteria 165:195 A novel member of Acidobacteria was isolated from a microbial mat growing on a geothermally heated dead tree trunk in Hawai'i Volcanoes National Park (HI, USA). 27692038 11 83 theme 16S 1334:1336 arg1 gene 1343:1346 the 16S rRNA gene 1330:1346 the 16S rRNA gene 1330:1346 A comparative genome analysis revealed an average nucleotide identity of 72.2 % between PMMR2T and its nearest cultured phylogenetic neighbour, Acidobacterium capsulatum ATCC 51196T (=JCM 7670T); analysis of the 16S rRNA gene revealed a 96.8 % sequence identity with Acidobacterium capsulatum ATCC 51196T. 27692038 0 84 theme ailaaui 49:55 arg1 sp 57:58 Acidobacterium ailaaui sp 34:58 Acidobacterium ailaaui sp 34:58 Isolation and characterization of Acidobacterium ailaaui sp. 27692038 9 85 theme membrane 1033:1040 arg1 acids 1048:1052 Major membrane fatty acids 1027:1052 Major membrane fatty acids 1027:1052 Major membrane fatty acids included iso-C15 : 0 and iso-C17 : 0. 27692038 6 86 theme genomic 636:642 arg1 analysis 644:651 a genomic analysis 634:651 a genomic analysis 634:651 However, results of a genomic analysis suggested that various polysaccharides might be hydrolysed as carbon sources, and evidence for pectin degradation was observed in liquid cultures. 27692038 7 87 theme genomic 802:808 arg1 analysis 810:817 A genomic analysis 800:817 A genomic analysis 800:817 A genomic analysis also revealed genes for a Group 1f uptake hydrogenase; assays with liquid cultures confirmed hydrogen consumption, including uptake at sub-atmospheric concentrations. 27692038 4 88 dep occurred 448:455 arg1 optimum 537:543 optimum 537:543 optimum 537:543 Growth occurred aerobically from 15 to 55 °C (optimum, 40 °C) and at pH values from 4.5 to 7.0 (optimum, 6.5). 27692038 11 89 theme genome 1136:1141 arg1 analysis 1143:1150 A comparative genome analysis 1122:1150 A comparative genome analysis 1122:1150 A comparative genome analysis revealed an average nucleotide identity of 72.2 % between PMMR2T and its nearest cultured phylogenetic neighbour, Acidobacterium capsulatum ATCC 51196T (=JCM 7670T); analysis of the 16S rRNA gene revealed a 96.8 % sequence identity with Acidobacterium capsulatum ATCC 51196T. 27692038 2 90 theme i 289:289 arg1 Volcanoes 291:299 Hawai'i Volcanoes National Park 283:313 Hawai'i Volcanoes National Park (HI, USA) 283:323 A novel member of Acidobacteria was isolated from a microbial mat growing on a geothermally heated dead tree trunk in Hawai'i Volcanoes National Park (HI, USA). 27375657 4 0 theme RR-stained 543:552 arg1 capsules 554:561 smaller RR-stained capsules 535:561 smaller RR-stained capsules 535:561 Most of the accessions released smaller RR-stained capsules compared to the Col-0 reference. 27375657 7 1 theme Pontamine 1093:1101 arg1 staining 1119:1126 altered Pontamine Fast Scarlet 4B staining 1085:1126 altered Pontamine Fast Scarlet 4B staining of cellulose 1085:1139 In addition, most of the natural variants had altered Pontamine Fast Scarlet 4B staining of cellulose and significantly reduced birefringence of crystalline structures. 27375657 12 2 theme accession 2029:2037 arg1 defects 2004:2010 the mucilage defects 1991:2010 the mucilage defects of a muci10-like accession 1991:2037 Although, we could not pinpoint any causal polymorphisms in this gene, constitutive expression of fluorescently-tagged MUCI10 proteins complemented the mucilage defects of a muci10-like accession. 27375657 5 3 with coatings 775:782 arg1 appearance 811:820 a deceptively similar appearance 789:820 a deceptively similar appearance 789:820 By biochemically characterizing the phenotypes of 25 of these accessions in greater detail, we discovered that distinct changes in polysaccharide structure resulted in gelatinous coatings with a deceptively similar appearance. 27375657 10 4 theme multiple 1568:1575 arg1 loci 1577:1580 multiple loci 1568:1580 multiple loci 1568:1580 This suggests that polymorphisms at multiple loci are likely responsible for the observed mucilage structure. 27375657 5 5 theme 25 646:647 arg1 phenotypes 632:641 the phenotypes 628:641 the phenotypes of 25 of these accessions 628:667 By biochemically characterizing the phenotypes of 25 of these accessions in greater detail, we discovered that distinct changes in polysaccharide structure resulted in gelatinous coatings with a deceptively similar appearance. 27375657 9 6 theme Western 1422:1428 arg1 Europe 1430:1435 Western Europe 1422:1435 Western Europe 1422:1435 Although, the accessions described in this study were primarily collected from Western Europe, they form five different phenotypic classes based on the combined results of our experiments. 27375657 6 7 theme remarkable 897:906 arg1 variation 908:916 a remarkable variation 895:916 a remarkable variation (from 50 to 200% of Col-0 levels) in the content of galactose and mannose, which are important subunits of heteromannan 895:1036 Monosaccharide composition analysis of total mucilage extracts revealed a remarkable variation (from 50 to 200% of Col-0 levels) in the content of galactose and mannose, which are important subunits of heteromannan. 27375657 14 8 theme wall 2240:2243 arg1 organization 2245:2256 plant cell wall organization 2229:2256 plant cell wall organization 2229:2256 Therefore, this collection of publicly-available variants should provide insight into plant cell wall organization and facilitate the discovery of genes that regulate polysaccharide biosynthesis. 27375657 11 9 theme MUCILAGE-RELATED10 1663:1680 arg1 transcription 1646:1658 The transcription 1642:1658 The transcription 1642:1658 The transcription of MUCILAGE-RELATED10 (MUCI10), which encodes a key enzyme for galactoglucomannan synthesis, was severely reduced in multiple variants that phenocopied the muci10-1 insertion mutant. 27375657 11 9 theme MUCILAGE-RELATED10 1663:1680 arg1 enzyme 1712:1717 a key enzyme 1706:1717 a key enzyme for galactoglucomannan synthesis 1706:1750 The transcription of MUCILAGE-RELATED10 (MUCI10), which encodes a key enzyme for galactoglucomannan synthesis, was severely reduced in multiple variants that phenocopied the muci10-1 insertion mutant. 27375657 7 10 theme natural 1064:1070 arg1 variants 1072:1079 the natural variants 1060:1079 the natural variants 1060:1079 In addition, most of the natural variants had altered Pontamine Fast Scarlet 4B staining of cellulose and significantly reduced birefringence of crystalline structures. 27375657 14 11 theme plant 2229:2233 arg1 organization 2245:2256 plant cell wall organization 2229:2256 plant cell wall organization 2229:2256 Therefore, this collection of publicly-available variants should provide insight into plant cell wall organization and facilitate the discovery of genes that regulate polysaccharide biosynthesis. 27375657 2 12 theme red 297:299 arg1 dye 306:308 the ruthenium red (RR) dye 283:308 the ruthenium red (RR) dye 283:308 Since mucilage is rich in pectin, its architecture can be visualized with the ruthenium red (RR) dye. 27375657 1 13 theme cell 182:185 arg1 polysaccharides 192:206 cell wall polysaccharides 182:206 cell wall polysaccharides 182:206 Hydrated Arabidopsis thaliana seeds are coated by a gelatinous layer called mucilage, which is mainly composed of cell wall polysaccharides. 27375657 9 14 theme different 1453:1461 arg1 classes 1474:1480 five different phenotypic classes 1448:1480 five different phenotypic classes based on the combined results of our experiments 1448:1529 Although, the accessions described in this study were primarily collected from Western Europe, they form five different phenotypic classes based on the combined results of our experiments. 27375657 12 15 theme proteins 1969:1976 arg1 expression 1927:1936 constitutive expression 1914:1936 constitutive expression of fluorescently-tagged MUCI10 proteins 1914:1976 Although, we could not pinpoint any causal polymorphisms in this gene, constitutive expression of fluorescently-tagged MUCI10 proteins complemented the mucilage defects of a muci10-like accession. 27375657 6 16 theme levels 944:949 arg1 % 933:933 50 to 200% 924:933 50 to 200% of Col-0 levels 924:949 Monosaccharide composition analysis of total mucilage extracts revealed a remarkable variation (from 50 to 200% of Col-0 levels) in the content of galactose and mannose, which are important subunits of heteromannan. 27375657 6 16 theme levels 944:949 arg1 levels 944:949 Col-0 levels 938:949 Col-0 levels 938:949 Monosaccharide composition analysis of total mucilage extracts revealed a remarkable variation (from 50 to 200% of Col-0 levels) in the content of galactose and mannose, which are important subunits of heteromannan. 27375657 6 17 dep 200 930:932 arg1 to 927:928 to 927:928 to 927:928 Monosaccharide composition analysis of total mucilage extracts revealed a remarkable variation (from 50 to 200% of Col-0 levels) in the content of galactose and mannose, which are important subunits of heteromannan. 27375657 10 18 theme mucilage 1622:1629 arg1 structure 1631:1639 the observed mucilage structure 1609:1639 the observed mucilage structure 1609:1639 This suggests that polymorphisms at multiple loci are likely responsible for the observed mucilage structure. 27375657 14 19 theme publicly-available 2173:2190 arg1 variants 2192:2199 publicly-available variants 2173:2199 publicly-available variants 2173:2199 Therefore, this collection of publicly-available variants should provide insight into plant cell wall organization and facilitate the discovery of genes that regulate polysaccharide biosynthesis. 27375657 11 20 theme insertion 1825:1833 arg1 mutant 1835:1840 the muci10-1 insertion mutant 1812:1840 the muci10-1 insertion mutant 1812:1840 The transcription of MUCILAGE-RELATED10 (MUCI10), which encodes a key enzyme for galactoglucomannan synthesis, was severely reduced in multiple variants that phenocopied the muci10-1 insertion mutant. 27375657 1 21 theme gelatinous 120:129 arg1 layer 131:135 a gelatinous layer 118:135 a gelatinous layer 118:135 Hydrated Arabidopsis thaliana seeds are coated by a gelatinous layer called mucilage, which is mainly composed of cell wall polysaccharides. 27375657 9 22 theme combined 1495:1502 arg1 results 1504:1510 the combined results 1491:1510 the combined results of our experiments 1491:1529 Although, the accessions described in this study were primarily collected from Western Europe, they form five different phenotypic classes based on the combined results of our experiments. 27375657 5 23 theme polysaccharide 727:740 arg1 structure 742:750 polysaccharide structure 727:750 polysaccharide structure 727:750 By biochemically characterizing the phenotypes of 25 of these accessions in greater detail, we discovered that distinct changes in polysaccharide structure resulted in gelatinous coatings with a deceptively similar appearance. 27375657 6 24 theme mannose 984:990 arg1 content 959:965 the content 955:965 the content of galactose and mannose, which are important subunits of heteromannan 955:1036 Monosaccharide composition analysis of total mucilage extracts revealed a remarkable variation (from 50 to 200% of Col-0 levels) in the content of galactose and mannose, which are important subunits of heteromannan. 27375657 0 25 from Variation 18:26 arg1 Arabidopsis 31:41 Arabidopsis 31:41 Arabidopsis 31:41 Extensive Natural Variation in Arabidopsis Seed Mucilage Structure. 27375657 8 26 theme amounts 1317:1323 arg1 presence 1295:1302 the presence 1291:1302 the presence of different amounts of hemicellulose 1291:1340 This indicates that the production or organization of cellulose may be affected by the presence of different amounts of hemicellulose. 27375657 11 27 theme multiple 1777:1784 arg1 variants 1786:1793 multiple variants 1777:1793 multiple variants that phenocopied the muci10-1 insertion mutant 1777:1840 The transcription of MUCILAGE-RELATED10 (MUCI10), which encodes a key enzyme for galactoglucomannan synthesis, was severely reduced in multiple variants that phenocopied the muci10-1 insertion mutant. 27375657 13 28 theme transcriptional 2106:2120 arg1 regulator 2122:2130 a transcriptional regulator 2104:2130 a transcriptional regulator of MUCI10 2104:2140 This leads us to hypothesize that some accessions might disrupt a transcriptional regulator of MUCI10. 27375657 12 29 theme constitutive 1914:1925 arg1 expression 1927:1936 constitutive expression 1914:1936 constitutive expression of fluorescently-tagged MUCI10 proteins 1914:1976 Although, we could not pinpoint any causal polymorphisms in this gene, constitutive expression of fluorescently-tagged MUCI10 proteins complemented the mucilage defects of a muci10-like accession. 27375657 9 30 theme experiments 1519:1529 arg1 results 1504:1510 the combined results 1491:1510 the combined results of our experiments 1491:1529 Although, the accessions described in this study were primarily collected from Western Europe, they form five different phenotypic classes based on the combined results of our experiments. 27375657 6 31 theme galactose 970:978 arg1 content 959:965 the content 955:965 the content of galactose and mannose, which are important subunits of heteromannan 955:1036 Monosaccharide composition analysis of total mucilage extracts revealed a remarkable variation (from 50 to 200% of Col-0 levels) in the content of galactose and mannose, which are important subunits of heteromannan. 27375657 8 32 theme hemicellulose 1328:1340 arg1 hemicellulose 1328:1340 hemicellulose 1328:1340 hemicellulose 1328:1340 This indicates that the production or organization of cellulose may be affected by the presence of different amounts of hemicellulose. 27375657 8 32 theme hemicellulose 1328:1340 arg1 amounts 1317:1323 different amounts 1307:1323 different amounts of hemicellulose 1307:1340 This indicates that the production or organization of cellulose may be affected by the presence of different amounts of hemicellulose. 27375657 7 33 theme crystalline 1184:1194 arg1 structures 1196:1205 crystalline structures 1184:1205 crystalline structures 1184:1205 In addition, most of the natural variants had altered Pontamine Fast Scarlet 4B staining of cellulose and significantly reduced birefringence of crystalline structures. 27375657 1 34 theme Hydrated 68:75 arg1 seeds 98:102 Hydrated Arabidopsis thaliana seeds 68:102 Hydrated Arabidopsis thaliana seeds 68:102 Hydrated Arabidopsis thaliana seeds are coated by a gelatinous layer called mucilage, which is mainly composed of cell wall polysaccharides. 27375657 1 35 theme thaliana 89:96 arg1 seeds 98:102 Hydrated Arabidopsis thaliana seeds 68:102 Hydrated Arabidopsis thaliana seeds 68:102 Hydrated Arabidopsis thaliana seeds are coated by a gelatinous layer called mucilage, which is mainly composed of cell wall polysaccharides. 27375657 0 36 theme Extensive 0:8 arg1 Variation 18:26 Extensive Natural Variation 0:26 Extensive Natural Variation in Arabidopsis 0:41 Extensive Natural Variation in Arabidopsis Seed Mucilage Structure. 27375657 8 37 dep production 1232:1241 arg1 the 1228:1230 the 1228:1230 the 1228:1230 This indicates that the production or organization of cellulose may be affected by the presence of different amounts of hemicellulose. 27375657 14 38 theme polysaccharide 2310:2323 arg1 biosynthesis 2325:2336 polysaccharide biosynthesis 2310:2336 polysaccharide biosynthesis 2310:2336 Therefore, this collection of publicly-available variants should provide insight into plant cell wall organization and facilitate the discovery of genes that regulate polysaccharide biosynthesis. 27375657 7 39 theme cellulose 1131:1139 arg1 staining 1119:1126 altered Pontamine Fast Scarlet 4B staining 1085:1126 altered Pontamine Fast Scarlet 4B staining of cellulose 1085:1139 In addition, most of the natural variants had altered Pontamine Fast Scarlet 4B staining of cellulose and significantly reduced birefringence of crystalline structures. 27375657 6 40 theme extracts 877:884 arg1 analysis 850:857 Monosaccharide composition analysis 823:857 Monosaccharide composition analysis of total mucilage extracts 823:884 Monosaccharide composition analysis of total mucilage extracts revealed a remarkable variation (from 50 to 200% of Col-0 levels) in the content of galactose and mannose, which are important subunits of heteromannan. 27375657 5 41 theme gelatinous 764:773 arg1 coatings 775:782 gelatinous coatings 764:782 gelatinous coatings with a deceptively similar appearance 764:820 By biochemically characterizing the phenotypes of 25 of these accessions in greater detail, we discovered that distinct changes in polysaccharide structure resulted in gelatinous coatings with a deceptively similar appearance. 27375657 12 42 theme causal 1879:1884 arg1 polymorphisms 1886:1898 any causal polymorphisms 1875:1898 any causal polymorphisms in this gene 1875:1911 Although, we could not pinpoint any causal polymorphisms in this gene, constitutive expression of fluorescently-tagged MUCI10 proteins complemented the mucilage defects of a muci10-like accession. 27375657 6 43 theme total 862:866 arg1 extracts 877:884 total mucilage extracts 862:884 total mucilage extracts 862:884 Monosaccharide composition analysis of total mucilage extracts revealed a remarkable variation (from 50 to 200% of Col-0 levels) in the content of galactose and mannose, which are important subunits of heteromannan. 27375657 6 44 theme important 1003:1011 arg1 galactose 970:978 galactose 970:978 galactose 970:978 Monosaccharide composition analysis of total mucilage extracts revealed a remarkable variation (from 50 to 200% of Col-0 levels) in the content of galactose and mannose, which are important subunits of heteromannan. 27375657 6 44 theme important 1003:1011 arg1 subunits 1013:1020 important subunits 1003:1020 important subunits of heteromannan 1003:1036 Monosaccharide composition analysis of total mucilage extracts revealed a remarkable variation (from 50 to 200% of Col-0 levels) in the content of galactose and mannose, which are important subunits of heteromannan. 27375657 6 44 theme important 1003:1011 arg1 mannose 984:990 mannose 984:990 mannose 984:990 Monosaccharide composition analysis of total mucilage extracts revealed a remarkable variation (from 50 to 200% of Col-0 levels) in the content of galactose and mannose, which are important subunits of heteromannan. 27375657 3 45 theme natural 359:365 arg1 accessions 367:376 around 280 Arabidopsis natural accessions 336:376 around 280 Arabidopsis natural accessions 336:376 We screened the seeds of around 280 Arabidopsis natural accessions for variation in mucilage structure, and identified a large number of novel variants that differed from the Col-0 wild-type. 27375657 6 46 from % 933:933 arg1 variation 908:916 a remarkable variation 895:916 a remarkable variation (from 50 to 200% of Col-0 levels) in the content of galactose and mannose, which are important subunits of heteromannan 895:1036 Monosaccharide composition analysis of total mucilage extracts revealed a remarkable variation (from 50 to 200% of Col-0 levels) in the content of galactose and mannose, which are important subunits of heteromannan. 27375657 3 47 theme novel 448:452 arg1 variants 454:461 novel variants 448:461 novel variants that differed from the Col-0 wild-type 448:500 We screened the seeds of around 280 Arabidopsis natural accessions for variation in mucilage structure, and identified a large number of novel variants that differed from the Col-0 wild-type. 27375657 0 48 theme Mucilage 48:55 arg1 Structure 57:65 Mucilage Structure 48:65 Mucilage Structure 48:65 Extensive Natural Variation in Arabidopsis Seed Mucilage Structure. 27375657 11 49 theme galactoglucomannan 1723:1740 arg1 synthesis 1742:1750 galactoglucomannan synthesis 1723:1750 galactoglucomannan synthesis 1723:1750 The transcription of MUCILAGE-RELATED10 (MUCI10), which encodes a key enzyme for galactoglucomannan synthesis, was severely reduced in multiple variants that phenocopied the muci10-1 insertion mutant. 27375657 10 50 from loci 1577:1580 arg1 polymorphisms 1551:1563 polymorphisms 1551:1563 polymorphisms at multiple loci 1551:1580 This suggests that polymorphisms at multiple loci are likely responsible for the observed mucilage structure. 27375657 14 51 theme genes 2290:2294 arg1 discovery 2277:2285 the discovery 2273:2285 the discovery of genes that regulate polysaccharide biosynthesis 2273:2336 Therefore, this collection of publicly-available variants should provide insight into plant cell wall organization and facilitate the discovery of genes that regulate polysaccharide biosynthesis. 27375657 4 52 theme Col-0 579:583 arg1 reference 585:593 the Col-0 reference 575:593 the Col-0 reference 575:593 Most of the accessions released smaller RR-stained capsules compared to the Col-0 reference. 27375657 7 53 theme altered 1085:1091 arg1 staining 1119:1126 altered Pontamine Fast Scarlet 4B staining 1085:1126 altered Pontamine Fast Scarlet 4B staining of cellulose 1085:1139 In addition, most of the natural variants had altered Pontamine Fast Scarlet 4B staining of cellulose and significantly reduced birefringence of crystalline structures. 27375657 4 54 theme smaller 535:541 arg1 capsules 554:561 smaller RR-stained capsules 535:561 smaller RR-stained capsules 535:561 Most of the accessions released smaller RR-stained capsules compared to the Col-0 reference. 27375657 12 55 theme muci10-like 2017:2027 arg1 accession 2029:2037 a muci10-like accession 2015:2037 a muci10-like accession 2015:2037 Although, we could not pinpoint any causal polymorphisms in this gene, constitutive expression of fluorescently-tagged MUCI10 proteins complemented the mucilage defects of a muci10-like accession. 27375657 6 56 from variation 908:916 arg1 content 959:965 the content 955:965 the content of galactose and mannose, which are important subunits of heteromannan 955:1036 Monosaccharide composition analysis of total mucilage extracts revealed a remarkable variation (from 50 to 200% of Col-0 levels) in the content of galactose and mannose, which are important subunits of heteromannan. 27375657 3 57 theme Col-0 486:490 arg1 wild-type 492:500 the Col-0 wild-type 482:500 the Col-0 wild-type 482:500 We screened the seeds of around 280 Arabidopsis natural accessions for variation in mucilage structure, and identified a large number of novel variants that differed from the Col-0 wild-type. 27375657 7 58 theme Scarlet 1108:1114 arg1 staining 1119:1126 altered Pontamine Fast Scarlet 4B staining 1085:1126 altered Pontamine Fast Scarlet 4B staining of cellulose 1085:1139 In addition, most of the natural variants had altered Pontamine Fast Scarlet 4B staining of cellulose and significantly reduced birefringence of crystalline structures. 27375657 14 59 theme cell 2235:2238 arg1 organization 2245:2256 plant cell wall organization 2229:2256 plant cell wall organization 2229:2256 Therefore, this collection of publicly-available variants should provide insight into plant cell wall organization and facilitate the discovery of genes that regulate polysaccharide biosynthesis. 27375657 12 60 theme mucilage 1995:2002 arg1 defects 2004:2010 the mucilage defects 1991:2010 the mucilage defects of a muci10-like accession 1991:2037 Although, we could not pinpoint any causal polymorphisms in this gene, constitutive expression of fluorescently-tagged MUCI10 proteins complemented the mucilage defects of a muci10-like accession. 27375657 12 61 from polymorphisms 1886:1898 arg1 gene 1908:1911 this gene 1903:1911 this gene 1903:1911 Although, we could not pinpoint any causal polymorphisms in this gene, constitutive expression of fluorescently-tagged MUCI10 proteins complemented the mucilage defects of a muci10-like accession. 27375657 11 62 theme muci10-1 1816:1823 arg1 mutant 1835:1840 the muci10-1 insertion mutant 1812:1840 the muci10-1 insertion mutant 1812:1840 The transcription of MUCILAGE-RELATED10 (MUCI10), which encodes a key enzyme for galactoglucomannan synthesis, was severely reduced in multiple variants that phenocopied the muci10-1 insertion mutant. 27375657 5 63 theme greater 672:678 arg1 detail 680:685 greater detail 672:685 greater detail 672:685 By biochemically characterizing the phenotypes of 25 of these accessions in greater detail, we discovered that distinct changes in polysaccharide structure resulted in gelatinous coatings with a deceptively similar appearance. 27375657 2 64 theme ruthenium 287:295 arg1 dye 306:308 the ruthenium red (RR) dye 283:308 the ruthenium red (RR) dye 283:308 Since mucilage is rich in pectin, its architecture can be visualized with the ruthenium red (RR) dye. 27375657 1 65 theme wall 187:190 arg1 polysaccharides 192:206 cell wall polysaccharides 182:206 cell wall polysaccharides 182:206 Hydrated Arabidopsis thaliana seeds are coated by a gelatinous layer called mucilage, which is mainly composed of cell wall polysaccharides. 27375657 5 66 from changes 716:722 arg1 structure 742:750 polysaccharide structure 727:750 polysaccharide structure 727:750 By biochemically characterizing the phenotypes of 25 of these accessions in greater detail, we discovered that distinct changes in polysaccharide structure resulted in gelatinous coatings with a deceptively similar appearance. 27375657 9 67 theme phenotypic 1463:1472 arg1 classes 1474:1480 five different phenotypic classes 1448:1480 five different phenotypic classes based on the combined results of our experiments 1448:1529 Although, the accessions described in this study were primarily collected from Western Europe, they form five different phenotypic classes based on the combined results of our experiments. 27375657 12 68 theme MUCI10 1962:1967 arg1 proteins 1969:1976 fluorescently-tagged MUCI10 proteins 1941:1976 fluorescently-tagged MUCI10 proteins 1941:1976 Although, we could not pinpoint any causal polymorphisms in this gene, constitutive expression of fluorescently-tagged MUCI10 proteins complemented the mucilage defects of a muci10-like accession. 27375657 6 69 theme Col-0 938:942 arg1 levels 944:949 Col-0 levels 938:949 Col-0 levels 938:949 Monosaccharide composition analysis of total mucilage extracts revealed a remarkable variation (from 50 to 200% of Col-0 levels) in the content of galactose and mannose, which are important subunits of heteromannan. 27375657 8 70 theme cellulose 1262:1270 arg1 production 1232:1241 production 1232:1241 production 1232:1241 This indicates that the production or organization of cellulose may be affected by the presence of different amounts of hemicellulose. 27375657 8 70 theme cellulose 1262:1270 arg1 organization 1246:1257 organization 1246:1257 organization 1246:1257 This indicates that the production or organization of cellulose may be affected by the presence of different amounts of hemicellulose. 27375657 10 71 theme observed 1613:1620 arg1 structure 1631:1639 the observed mucilage structure 1609:1639 the observed mucilage structure 1609:1639 This suggests that polymorphisms at multiple loci are likely responsible for the observed mucilage structure. 27375657 5 72 theme accessions 658:667 arg1 accessions 658:667 these accessions 652:667 these accessions 652:667 By biochemically characterizing the phenotypes of 25 of these accessions in greater detail, we discovered that distinct changes in polysaccharide structure resulted in gelatinous coatings with a deceptively similar appearance. 27375657 5 72 theme accessions 658:667 arg1 25 646:647 25 646:647 25 646:647 By biochemically characterizing the phenotypes of 25 of these accessions in greater detail, we discovered that distinct changes in polysaccharide structure resulted in gelatinous coatings with a deceptively similar appearance. 27375657 13 73 theme MUCI10 2135:2140 arg1 regulator 2122:2130 a transcriptional regulator 2104:2130 a transcriptional regulator of MUCI10 2104:2140 This leads us to hypothesize that some accessions might disrupt a transcriptional regulator of MUCI10. 27375657 7 74 contain had 1081:1083 arg1 most 1052:1055 most 1052:1055 most 1052:1055 In addition, most of the natural variants had altered Pontamine Fast Scarlet 4B staining of cellulose and significantly reduced birefringence of crystalline structures. 27375657 7 74 contain had 1081:1083 arg2 staining 1119:1126 altered Pontamine Fast Scarlet 4B staining 1085:1126 altered Pontamine Fast Scarlet 4B staining of cellulose 1085:1139 In addition, most of the natural variants had altered Pontamine Fast Scarlet 4B staining of cellulose and significantly reduced birefringence of crystalline structures. 27375657 7 74 contain had 1081:1083 arg1 variants 1072:1079 the natural variants 1060:1079 the natural variants 1060:1079 In addition, most of the natural variants had altered Pontamine Fast Scarlet 4B staining of cellulose and significantly reduced birefringence of crystalline structures. 27375657 7 75 theme structures 1196:1205 arg1 birefringence 1167:1179 birefringence 1167:1179 birefringence of crystalline structures 1167:1205 In addition, most of the natural variants had altered Pontamine Fast Scarlet 4B staining of cellulose and significantly reduced birefringence of crystalline structures. 27375657 6 76 theme Monosaccharide 823:836 arg1 analysis 850:857 Monosaccharide composition analysis 823:857 Monosaccharide composition analysis of total mucilage extracts 823:884 Monosaccharide composition analysis of total mucilage extracts revealed a remarkable variation (from 50 to 200% of Col-0 levels) in the content of galactose and mannose, which are important subunits of heteromannan. 27375657 8 77 theme different 1307:1315 arg1 hemicellulose 1328:1340 hemicellulose 1328:1340 hemicellulose 1328:1340 This indicates that the production or organization of cellulose may be affected by the presence of different amounts of hemicellulose. 27375657 8 77 theme different 1307:1315 arg1 amounts 1317:1323 different amounts 1307:1323 different amounts of hemicellulose 1307:1340 This indicates that the production or organization of cellulose may be affected by the presence of different amounts of hemicellulose. 27375657 3 78 from variation 382:390 arg1 structure 404:412 mucilage structure 395:412 mucilage structure 395:412 We screened the seeds of around 280 Arabidopsis natural accessions for variation in mucilage structure, and identified a large number of novel variants that differed from the Col-0 wild-type. 27375657 12 79 theme fluorescently-tagged 1941:1960 arg1 proteins 1969:1976 fluorescently-tagged MUCI10 proteins 1941:1976 fluorescently-tagged MUCI10 proteins 1941:1976 Although, we could not pinpoint any causal polymorphisms in this gene, constitutive expression of fluorescently-tagged MUCI10 proteins complemented the mucilage defects of a muci10-like accession. 27375657 5 80 theme distinct 707:714 arg1 changes 716:722 distinct changes 707:722 distinct changes in polysaccharide structure 707:750 By biochemically characterizing the phenotypes of 25 of these accessions in greater detail, we discovered that distinct changes in polysaccharide structure resulted in gelatinous coatings with a deceptively similar appearance. 27375657 1 81 theme Arabidopsis 77:87 arg1 seeds 98:102 Hydrated Arabidopsis thaliana seeds 68:102 Hydrated Arabidopsis thaliana seeds 68:102 Hydrated Arabidopsis thaliana seeds are coated by a gelatinous layer called mucilage, which is mainly composed of cell wall polysaccharides. 27375657 0 82 theme Natural 10:16 arg1 Variation 18:26 Extensive Natural Variation 0:26 Extensive Natural Variation in Arabidopsis 0:41 Extensive Natural Variation in Arabidopsis Seed Mucilage Structure. 27375657 2 83 from rich 227:230 arg1 pectin 235:240 pectin 235:240 pectin 235:240 Since mucilage is rich in pectin, its architecture can be visualized with the ruthenium red (RR) dye. 27375657 3 84 theme Arabidopsis 347:357 arg1 accessions 367:376 around 280 Arabidopsis natural accessions 336:376 around 280 Arabidopsis natural accessions 336:376 We screened the seeds of around 280 Arabidopsis natural accessions for variation in mucilage structure, and identified a large number of novel variants that differed from the Col-0 wild-type. 27375657 3 85 theme mucilage 395:402 arg1 structure 404:412 mucilage structure 395:412 mucilage structure 395:412 We screened the seeds of around 280 Arabidopsis natural accessions for variation in mucilage structure, and identified a large number of novel variants that differed from the Col-0 wild-type. 27375657 5 86 theme similar 803:809 arg1 appearance 811:820 a deceptively similar appearance 789:820 a deceptively similar appearance 789:820 By biochemically characterizing the phenotypes of 25 of these accessions in greater detail, we discovered that distinct changes in polysaccharide structure resulted in gelatinous coatings with a deceptively similar appearance. 27375657 2 87 from pectin 235:240 arg1 rich 227:230 rich 227:230 rich 227:230 Since mucilage is rich in pectin, its architecture can be visualized with the ruthenium red (RR) dye. 27375657 6 88 theme heteromannan 1025:1036 arg1 galactose 970:978 galactose 970:978 galactose 970:978 Monosaccharide composition analysis of total mucilage extracts revealed a remarkable variation (from 50 to 200% of Col-0 levels) in the content of galactose and mannose, which are important subunits of heteromannan. 27375657 6 88 theme heteromannan 1025:1036 arg1 subunits 1013:1020 important subunits 1003:1020 important subunits of heteromannan 1003:1036 Monosaccharide composition analysis of total mucilage extracts revealed a remarkable variation (from 50 to 200% of Col-0 levels) in the content of galactose and mannose, which are important subunits of heteromannan. 27375657 6 88 theme heteromannan 1025:1036 arg1 mannose 984:990 mannose 984:990 mannose 984:990 Monosaccharide composition analysis of total mucilage extracts revealed a remarkable variation (from 50 to 200% of Col-0 levels) in the content of galactose and mannose, which are important subunits of heteromannan. 27375657 3 89 theme large 432:436 arg1 number 438:443 a large number 430:443 a large number of novel variants that differed from the Col-0 wild-type 430:500 We screened the seeds of around 280 Arabidopsis natural accessions for variation in mucilage structure, and identified a large number of novel variants that differed from the Col-0 wild-type. 27375657 7 90 theme 4B 1116:1117 arg1 staining 1119:1126 altered Pontamine Fast Scarlet 4B staining 1085:1126 altered Pontamine Fast Scarlet 4B staining of cellulose 1085:1139 In addition, most of the natural variants had altered Pontamine Fast Scarlet 4B staining of cellulose and significantly reduced birefringence of crystalline structures. 27375657 6 91 theme mucilage 868:875 arg1 extracts 877:884 total mucilage extracts 862:884 total mucilage extracts 862:884 Monosaccharide composition analysis of total mucilage extracts revealed a remarkable variation (from 50 to 200% of Col-0 levels) in the content of galactose and mannose, which are important subunits of heteromannan. 27375657 7 92 theme Fast 1103:1106 arg1 staining 1119:1126 altered Pontamine Fast Scarlet 4B staining 1085:1126 altered Pontamine Fast Scarlet 4B staining of cellulose 1085:1139 In addition, most of the natural variants had altered Pontamine Fast Scarlet 4B staining of cellulose and significantly reduced birefringence of crystalline structures. 27375657 3 93 theme accessions 367:376 arg1 seeds 327:331 the seeds 323:331 the seeds of around 280 Arabidopsis natural accessions 323:376 We screened the seeds of around 280 Arabidopsis natural accessions for variation in mucilage structure, and identified a large number of novel variants that differed from the Col-0 wild-type. 27375657 3 94 theme variants 454:461 arg1 number 438:443 a large number 430:443 a large number of novel variants that differed from the Col-0 wild-type 430:500 We screened the seeds of around 280 Arabidopsis natural accessions for variation in mucilage structure, and identified a large number of novel variants that differed from the Col-0 wild-type. 27375657 6 95 theme composition 838:848 arg1 analysis 850:857 Monosaccharide composition analysis 823:857 Monosaccharide composition analysis of total mucilage extracts 823:884 Monosaccharide composition analysis of total mucilage extracts revealed a remarkable variation (from 50 to 200% of Col-0 levels) in the content of galactose and mannose, which are important subunits of heteromannan. 27375657 11 96 theme key 1708:1710 arg1 transcription 1646:1658 The transcription 1642:1658 The transcription 1642:1658 The transcription of MUCILAGE-RELATED10 (MUCI10), which encodes a key enzyme for galactoglucomannan synthesis, was severely reduced in multiple variants that phenocopied the muci10-1 insertion mutant. 27375657 11 96 theme key 1708:1710 arg1 enzyme 1712:1717 a key enzyme 1706:1717 a key enzyme for galactoglucomannan synthesis 1706:1750 The transcription of MUCILAGE-RELATED10 (MUCI10), which encodes a key enzyme for galactoglucomannan synthesis, was severely reduced in multiple variants that phenocopied the muci10-1 insertion mutant. 27375657 2 97 theme RR 302:303 arg1 dye 306:308 the ruthenium red (RR) dye 283:308 the ruthenium red (RR) dye 283:308 Since mucilage is rich in pectin, its architecture can be visualized with the ruthenium red (RR) dye. 27375657 14 98 theme variants 2192:2199 arg1 collection 2159:2168 this collection 2154:2168 this collection of publicly-available variants 2154:2199 Therefore, this collection of publicly-available variants should provide insight into plant cell wall organization and facilitate the discovery of genes that regulate polysaccharide biosynthesis. 28836293 0 0 theme high-grade 95:104 arg1 gliomas 106:112 high-grade gliomas 95:112 high-grade gliomas 95:112 Genetic driver mutations define the expression signature and microenvironmental composition of high-grade gliomas. 28836293 5 1 theme key 847:849 arg1 cells 837:841 microenvironmental, non-neoplastic cells 802:841 microenvironmental, non-neoplastic cells 802:841 However, this question is of utmost importance since microenvironmental, non-neoplastic cells are key components of the most radiotherapy- and chemotherapy-resistant niches of the tumor. 28836293 5 1 theme key 847:849 arg1 components 851:860 key components 847:860 key components of the most radiotherapy- and chemotherapy-resistant niches of the tumor 847:933 However, this question is of utmost importance since microenvironmental, non-neoplastic cells are key components of the most radiotherapy- and chemotherapy-resistant niches of the tumor. 28836293 6 2 theme HGG 1004:1006 arg1 model 1014:1018 a versatile, reliable, and reproducible adult HGG mouse model 958:1018 a versatile, reliable, and reproducible adult HGG mouse model with NF1-silencing 958:1037 Our work demonstrates a versatile, reliable, and reproducible adult HGG mouse model with NF1-silencing as a driver mutation. 28836293 6 2 theme HGG 1004:1006 arg1 mutation 1051:1058 a driver mutation 1042:1058 a driver mutation 1042:1058 Our work demonstrates a versatile, reliable, and reproducible adult HGG mouse model with NF1-silencing as a driver mutation. 28836293 6 3 theme adult 998:1002 arg1 model 1014:1018 a versatile, reliable, and reproducible adult HGG mouse model 958:1018 a versatile, reliable, and reproducible adult HGG mouse model with NF1-silencing 958:1037 Our work demonstrates a versatile, reliable, and reproducible adult HGG mouse model with NF1-silencing as a driver mutation. 28836293 6 3 theme adult 998:1002 arg1 mutation 1051:1058 a driver mutation 1042:1058 a driver mutation 1042:1058 Our work demonstrates a versatile, reliable, and reproducible adult HGG mouse model with NF1-silencing as a driver mutation. 28836293 7 4 theme established 1223:1233 arg1 model 1266:1270 our established PDGFB-overexpressing HGG mouse model 1219:1270 our established PDGFB-overexpressing HGG mouse model 1219:1270 This model shows significant differences in tumor microenvironment, expression of subtype-specific markers, and response to standard therapy when compared to our established PDGFB-overexpressing HGG mouse model. 28836293 8 5 theme proneural 1352:1360 arg1 subtypes 1378:1385 human proneural and mesenchymal subtypes 1346:1385 human proneural and mesenchymal subtypes 1346:1385 PDGFB-overexpressing and NF1-silenced murine tumors closely cluster with human proneural and mesenchymal subtypes, as well as PDGFRA-amplified and NF1-deleted/mutant human tumors, respectively, at both the RNA and protein expression levels. 28836293 1 6 theme intra-tumoral 247:259 arg1 heterogeneity 261:273 intra-tumoral heterogeneity 247:273 intra-tumoral heterogeneity 247:273 High-grade gliomas (HGG), including glioblastomas, are characterized by invasive growth, resistance to therapy, and high inter- and intra-tumoral heterogeneity. 28836293 8 7 theme PDGFB-overexpressing 1273:1292 arg1 tumors 1318:1323 PDGFB-overexpressing and NF1-silenced murine tumors 1273:1323 PDGFB-overexpressing and NF1-silenced murine tumors 1273:1323 PDGFB-overexpressing and NF1-silenced murine tumors closely cluster with human proneural and mesenchymal subtypes, as well as PDGFRA-amplified and NF1-deleted/mutant human tumors, respectively, at both the RNA and protein expression levels. 28836293 6 8 theme reproducible 985:996 arg1 model 1014:1018 a versatile, reliable, and reproducible adult HGG mouse model 958:1018 a versatile, reliable, and reproducible adult HGG mouse model with NF1-silencing 958:1037 Our work demonstrates a versatile, reliable, and reproducible adult HGG mouse model with NF1-silencing as a driver mutation. 28836293 6 8 theme reproducible 985:996 arg1 mutation 1051:1058 a driver mutation 1042:1058 a driver mutation 1042:1058 Our work demonstrates a versatile, reliable, and reproducible adult HGG mouse model with NF1-silencing as a driver mutation. 28836293 8 9 theme RNA 1479:1481 arg1 levels 1506:1511 both the RNA and protein expression levels 1470:1511 levels 1506:1511 PDGFB-overexpressing and NF1-silenced murine tumors closely cluster with human proneural and mesenchymal subtypes, as well as PDGFRA-amplified and NF1-deleted/mutant human tumors, respectively, at both the RNA and protein expression levels. 28836293 0 10 theme gliomas 106:112 arg1 signature 47:55 expression signature 36:55 expression signature 36:55 Genetic driver mutations define the expression signature and microenvironmental composition of high-grade gliomas. 28836293 0 10 theme gliomas 106:112 arg1 composition 80:90 microenvironmental composition 61:90 microenvironmental composition 61:90 Genetic driver mutations define the expression signature and microenvironmental composition of high-grade gliomas. 28836293 2 11 theme histological 284:295 arg1 necrosis 344:351 pseudopalisading necrosis 327:351 pseudopalisading necrosis 327:351 The key histological hallmarks of glioblastoma are pseudopalisading necrosis and microvascular proliferation, which allow pathologists to distinguish glioblastoma from lower-grade gliomas. 28836293 2 11 theme histological 284:295 arg1 hallmarks 297:305 The key histological hallmarks 276:305 The key histological hallmarks of glioblastoma 276:321 The key histological hallmarks of glioblastoma are pseudopalisading necrosis and microvascular proliferation, which allow pathologists to distinguish glioblastoma from lower-grade gliomas. 28836293 3 12 theme microenvironment 597:612 arg1 composition 576:586 the composition 572:586 the composition of their microenvironment 572:612 In addition to being genetically and molecularly heterogeneous, HGG are also heterogeneous with respect to the composition of their microenvironment. 28836293 4 13 theme microenvironmental 644:661 arg1 heterogeneity 663:675 this microenvironmental heterogeneity 639:675 this microenvironmental heterogeneity 639:675 The question of whether this microenvironmental heterogeneity is driven by the molecular identity of the tumor remains controversial. 28836293 8 14 theme NF1-silenced 1298:1309 arg1 tumors 1318:1323 PDGFB-overexpressing and NF1-silenced murine tumors 1273:1323 PDGFB-overexpressing and NF1-silenced murine tumors 1273:1323 PDGFB-overexpressing and NF1-silenced murine tumors closely cluster with human proneural and mesenchymal subtypes, as well as PDGFRA-amplified and NF1-deleted/mutant human tumors, respectively, at both the RNA and protein expression levels. 28836293 5 15 theme tumor 929:933 arg1 niches 915:920 the most radiotherapy- and chemotherapy-resistant niches 865:920 the most radiotherapy- and chemotherapy-resistant niches of the tumor 865:933 However, this question is of utmost importance since microenvironmental, non-neoplastic cells are key components of the most radiotherapy- and chemotherapy-resistant niches of the tumor. 28836293 2 16 theme key 280:282 arg1 necrosis 344:351 pseudopalisading necrosis 327:351 pseudopalisading necrosis 327:351 The key histological hallmarks of glioblastoma are pseudopalisading necrosis and microvascular proliferation, which allow pathologists to distinguish glioblastoma from lower-grade gliomas. 28836293 2 16 theme key 280:282 arg1 hallmarks 297:305 The key histological hallmarks 276:305 The key histological hallmarks of glioblastoma 276:321 The key histological hallmarks of glioblastoma are pseudopalisading necrosis and microvascular proliferation, which allow pathologists to distinguish glioblastoma from lower-grade gliomas. 28836293 9 17 theme genetic 1586:1592 arg1 background 1594:1603 C57BL/6 genetic background 1578:1603 C57BL/6 genetic background 1578:1603 These models can be generated in fully immunocompetent mixed or C57BL/6 genetic background mice, and therefore can easily be incorporated into preclinical studies for cancer cell-specific or immune cell-targeting drug discovery studies. 28836293 7 18 theme HGG 1256:1258 arg1 model 1266:1270 our established PDGFB-overexpressing HGG mouse model 1219:1270 our established PDGFB-overexpressing HGG mouse model 1219:1270 This model shows significant differences in tumor microenvironment, expression of subtype-specific markers, and response to standard therapy when compared to our established PDGFB-overexpressing HGG mouse model. 28836293 6 19 theme reliable 971:978 arg1 model 1014:1018 a versatile, reliable, and reproducible adult HGG mouse model 958:1018 a versatile, reliable, and reproducible adult HGG mouse model with NF1-silencing 958:1037 Our work demonstrates a versatile, reliable, and reproducible adult HGG mouse model with NF1-silencing as a driver mutation. 28836293 6 19 theme reliable 971:978 arg1 mutation 1051:1058 a driver mutation 1042:1058 a driver mutation 1042:1058 Our work demonstrates a versatile, reliable, and reproducible adult HGG mouse model with NF1-silencing as a driver mutation. 28836293 7 20 theme mouse 1260:1264 arg1 model 1266:1270 our established PDGFB-overexpressing HGG mouse model 1219:1270 our established PDGFB-overexpressing HGG mouse model 1219:1270 This model shows significant differences in tumor microenvironment, expression of subtype-specific markers, and response to standard therapy when compared to our established PDGFB-overexpressing HGG mouse model. 28836293 5 21 theme chemotherapy-resistant 892:913 arg1 niches 915:920 the most radiotherapy- and chemotherapy-resistant niches 865:920 the most radiotherapy- and chemotherapy-resistant niches of the tumor 865:933 However, this question is of utmost importance since microenvironmental, non-neoplastic cells are key components of the most radiotherapy- and chemotherapy-resistant niches of the tumor. 28836293 7 22 from response 1173:1180 arg1 microenvironment 1111:1126 tumor microenvironment 1105:1126 tumor microenvironment 1105:1126 This model shows significant differences in tumor microenvironment, expression of subtype-specific markers, and response to standard therapy when compared to our established PDGFB-overexpressing HGG mouse model. 28836293 4 23 theme tumor 720:724 arg1 identity 704:711 the molecular identity 690:711 the molecular identity of the tumor 690:724 The question of whether this microenvironmental heterogeneity is driven by the molecular identity of the tumor remains controversial. 28836293 0 24 theme driver 8:13 arg1 mutations 15:23 Genetic driver mutations 0:23 Genetic driver mutations 0:23 Genetic driver mutations define the expression signature and microenvironmental composition of high-grade gliomas. 28836293 2 25 theme pseudopalisading 327:342 arg1 necrosis 344:351 pseudopalisading necrosis 327:351 pseudopalisading necrosis 327:351 The key histological hallmarks of glioblastoma are pseudopalisading necrosis and microvascular proliferation, which allow pathologists to distinguish glioblastoma from lower-grade gliomas. 28836293 2 25 theme pseudopalisading 327:342 arg1 hallmarks 297:305 The key histological hallmarks 276:305 The key histological hallmarks of glioblastoma 276:321 The key histological hallmarks of glioblastoma are pseudopalisading necrosis and microvascular proliferation, which allow pathologists to distinguish glioblastoma from lower-grade gliomas. 28836293 1 26 theme invasive 187:194 arg1 growth 196:201 invasive growth 187:201 invasive growth 187:201 High-grade gliomas (HGG), including glioblastomas, are characterized by invasive growth, resistance to therapy, and high inter- and intra-tumoral heterogeneity. 28836293 0 27 theme Genetic 0:6 arg1 mutations 15:23 Genetic driver mutations 0:23 Genetic driver mutations 0:23 Genetic driver mutations define the expression signature and microenvironmental composition of high-grade gliomas. 28836293 9 28 theme cell-targeting 1712:1725 arg1 discovery 1732:1740 cancer cell-specific or immune cell-targeting drug discovery studies 1681:1748 discovery 1732:1740 These models can be generated in fully immunocompetent mixed or C57BL/6 genetic background mice, and therefore can easily be incorporated into preclinical studies for cancer cell-specific or immune cell-targeting drug discovery studies. 28836293 7 29 theme standard 1185:1192 arg1 therapy 1194:1200 standard therapy 1185:1200 standard therapy 1185:1200 This model shows significant differences in tumor microenvironment, expression of subtype-specific markers, and response to standard therapy when compared to our established PDGFB-overexpressing HGG mouse model. 28836293 2 30 dep necrosis 344:351 arg1 allow 392:396 allow 392:396 allow pathologists to distinguish glioblastoma from lower-grade gliomas 392:462 The key histological hallmarks of glioblastoma are pseudopalisading necrosis and microvascular proliferation, which allow pathologists to distinguish glioblastoma from lower-grade gliomas. 28836293 9 31 theme background 1594:1603 arg1 mice 1605:1608 fully immunocompetent mixed or C57BL/6 genetic background mice 1547:1608 fully immunocompetent mixed or C57BL/6 genetic background mice 1547:1608 These models can be generated in fully immunocompetent mixed or C57BL/6 genetic background mice, and therefore can easily be incorporated into preclinical studies for cancer cell-specific or immune cell-targeting drug discovery studies. 28836293 5 32 theme niches 915:920 arg1 cells 837:841 microenvironmental, non-neoplastic cells 802:841 microenvironmental, non-neoplastic cells 802:841 However, this question is of utmost importance since microenvironmental, non-neoplastic cells are key components of the most radiotherapy- and chemotherapy-resistant niches of the tumor. 28836293 5 32 theme niches 915:920 arg1 components 851:860 key components 847:860 key components of the most radiotherapy- and chemotherapy-resistant niches of the tumor 847:933 However, this question is of utmost importance since microenvironmental, non-neoplastic cells are key components of the most radiotherapy- and chemotherapy-resistant niches of the tumor. 28836293 2 33 theme glioblastoma 310:321 arg1 necrosis 344:351 pseudopalisading necrosis 327:351 pseudopalisading necrosis 327:351 The key histological hallmarks of glioblastoma are pseudopalisading necrosis and microvascular proliferation, which allow pathologists to distinguish glioblastoma from lower-grade gliomas. 28836293 2 33 theme glioblastoma 310:321 arg1 hallmarks 297:305 The key histological hallmarks 276:305 The key histological hallmarks of glioblastoma 276:321 The key histological hallmarks of glioblastoma are pseudopalisading necrosis and microvascular proliferation, which allow pathologists to distinguish glioblastoma from lower-grade gliomas. 28836293 7 34 from differences 1090:1100 arg1 microenvironment 1111:1126 tumor microenvironment 1105:1126 tumor microenvironment 1105:1126 This model shows significant differences in tumor microenvironment, expression of subtype-specific markers, and response to standard therapy when compared to our established PDGFB-overexpressing HGG mouse model. 28836293 6 35 with model 1014:1018 arg1 NF1-silencing 1025:1037 NF1-silencing 1025:1037 NF1-silencing 1025:1037 Our work demonstrates a versatile, reliable, and reproducible adult HGG mouse model with NF1-silencing as a driver mutation. 28836293 6 36 theme driver 1044:1049 arg1 model 1014:1018 a versatile, reliable, and reproducible adult HGG mouse model 958:1018 a versatile, reliable, and reproducible adult HGG mouse model with NF1-silencing 958:1037 Our work demonstrates a versatile, reliable, and reproducible adult HGG mouse model with NF1-silencing as a driver mutation. 28836293 6 36 theme driver 1044:1049 arg1 mutation 1051:1058 a driver mutation 1042:1058 a driver mutation 1042:1058 Our work demonstrates a versatile, reliable, and reproducible adult HGG mouse model with NF1-silencing as a driver mutation. 28836293 8 37 theme protein 1487:1493 arg1 expression 1495:1504 protein expression 1487:1504 protein expression 1487:1504 PDGFB-overexpressing and NF1-silenced murine tumors closely cluster with human proneural and mesenchymal subtypes, as well as PDGFRA-amplified and NF1-deleted/mutant human tumors, respectively, at both the RNA and protein expression levels. 28836293 6 38 theme versatile 960:968 arg1 model 1014:1018 a versatile, reliable, and reproducible adult HGG mouse model 958:1018 a versatile, reliable, and reproducible adult HGG mouse model with NF1-silencing 958:1037 Our work demonstrates a versatile, reliable, and reproducible adult HGG mouse model with NF1-silencing as a driver mutation. 28836293 6 38 theme versatile 960:968 arg1 mutation 1051:1058 a driver mutation 1042:1058 a driver mutation 1042:1058 Our work demonstrates a versatile, reliable, and reproducible adult HGG mouse model with NF1-silencing as a driver mutation. 28836293 9 39 theme drug 1727:1730 arg1 discovery 1732:1740 cancer cell-specific or immune cell-targeting drug discovery studies 1681:1748 discovery 1732:1740 These models can be generated in fully immunocompetent mixed or C57BL/6 genetic background mice, and therefore can easily be incorporated into preclinical studies for cancer cell-specific or immune cell-targeting drug discovery studies. 28836293 9 40 theme mixed 1569:1573 arg1 mice 1605:1608 fully immunocompetent mixed or C57BL/6 genetic background mice 1547:1608 fully immunocompetent mixed or C57BL/6 genetic background mice 1547:1608 These models can be generated in fully immunocompetent mixed or C57BL/6 genetic background mice, and therefore can easily be incorporated into preclinical studies for cancer cell-specific or immune cell-targeting drug discovery studies. 28836293 4 41 theme molecular 694:702 arg1 identity 704:711 the molecular identity 690:711 the molecular identity of the tumor 690:724 The question of whether this microenvironmental heterogeneity is driven by the molecular identity of the tumor remains controversial. 28836293 0 42 theme expression 36:45 arg1 signature 47:55 expression signature 36:55 expression signature 36:55 Genetic driver mutations define the expression signature and microenvironmental composition of high-grade gliomas. 28836293 8 43 theme NF1-deleted/mutant 1420:1437 arg1 tumors 1445:1450 PDGFRA-amplified and NF1-deleted/mutant human tumors 1399:1450 PDGFRA-amplified and NF1-deleted/mutant human tumors 1399:1450 PDGFB-overexpressing and NF1-silenced murine tumors closely cluster with human proneural and mesenchymal subtypes, as well as PDGFRA-amplified and NF1-deleted/mutant human tumors, respectively, at both the RNA and protein expression levels. 28836293 5 44 theme utmost 778:783 arg1 importance 785:794 utmost importance 778:794 utmost importance 778:794 However, this question is of utmost importance since microenvironmental, non-neoplastic cells are key components of the most radiotherapy- and chemotherapy-resistant niches of the tumor. 28836293 7 45 theme PDGFB-overexpressing 1235:1254 arg1 model 1266:1270 our established PDGFB-overexpressing HGG mouse model 1219:1270 our established PDGFB-overexpressing HGG mouse model 1219:1270 This model shows significant differences in tumor microenvironment, expression of subtype-specific markers, and response to standard therapy when compared to our established PDGFB-overexpressing HGG mouse model. 28836293 0 46 dep signature 47:55 arg1 the 32:34 the 32:34 the 32:34 Genetic driver mutations define the expression signature and microenvironmental composition of high-grade gliomas. 28836293 7 47 theme tumor 1105:1109 arg1 microenvironment 1111:1126 tumor microenvironment 1105:1126 tumor microenvironment 1105:1126 This model shows significant differences in tumor microenvironment, expression of subtype-specific markers, and response to standard therapy when compared to our established PDGFB-overexpressing HGG mouse model. 28836293 2 48 theme lower-grade 444:454 arg1 gliomas 456:462 lower-grade gliomas 444:462 lower-grade gliomas 444:462 The key histological hallmarks of glioblastoma are pseudopalisading necrosis and microvascular proliferation, which allow pathologists to distinguish glioblastoma from lower-grade gliomas. 28836293 5 49 theme most 869:872 arg1 niches 915:920 the most radiotherapy- and chemotherapy-resistant niches 865:920 the most radiotherapy- and chemotherapy-resistant niches of the tumor 865:933 However, this question is of utmost importance since microenvironmental, non-neoplastic cells are key components of the most radiotherapy- and chemotherapy-resistant niches of the tumor. 28836293 9 50 theme C57BL/6 1578:1584 arg1 background 1594:1603 C57BL/6 genetic background 1578:1603 C57BL/6 genetic background 1578:1603 These models can be generated in fully immunocompetent mixed or C57BL/6 genetic background mice, and therefore can easily be incorporated into preclinical studies for cancer cell-specific or immune cell-targeting drug discovery studies. 28836293 8 51 theme human 1346:1350 arg1 subtypes 1378:1385 human proneural and mesenchymal subtypes 1346:1385 human proneural and mesenchymal subtypes 1346:1385 PDGFB-overexpressing and NF1-silenced murine tumors closely cluster with human proneural and mesenchymal subtypes, as well as PDGFRA-amplified and NF1-deleted/mutant human tumors, respectively, at both the RNA and protein expression levels. 28836293 8 52 theme expression 1495:1504 arg1 levels 1506:1511 both the RNA and protein expression levels 1470:1511 levels 1506:1511 PDGFB-overexpressing and NF1-silenced murine tumors closely cluster with human proneural and mesenchymal subtypes, as well as PDGFRA-amplified and NF1-deleted/mutant human tumors, respectively, at both the RNA and protein expression levels. 28836293 8 53 theme human 1439:1443 arg1 tumors 1445:1450 PDGFRA-amplified and NF1-deleted/mutant human tumors 1399:1450 PDGFRA-amplified and NF1-deleted/mutant human tumors 1399:1450 PDGFB-overexpressing and NF1-silenced murine tumors closely cluster with human proneural and mesenchymal subtypes, as well as PDGFRA-amplified and NF1-deleted/mutant human tumors, respectively, at both the RNA and protein expression levels. 28836293 5 54 theme radiotherapy- 874:886 arg1 niches 915:920 the most radiotherapy- and chemotherapy-resistant niches 865:920 the most radiotherapy- and chemotherapy-resistant niches of the tumor 865:933 However, this question is of utmost importance since microenvironmental, non-neoplastic cells are key components of the most radiotherapy- and chemotherapy-resistant niches of the tumor. 28836293 7 55 theme subtype-specific 1143:1158 arg1 markers 1160:1166 subtype-specific markers 1143:1166 subtype-specific markers 1143:1166 This model shows significant differences in tumor microenvironment, expression of subtype-specific markers, and response to standard therapy when compared to our established PDGFB-overexpressing HGG mouse model. 28836293 9 56 theme cancer 1681:1686 arg1 discovery 1732:1740 cancer cell-specific or immune cell-targeting drug discovery studies 1681:1748 discovery 1732:1740 These models can be generated in fully immunocompetent mixed or C57BL/6 genetic background mice, and therefore can easily be incorporated into preclinical studies for cancer cell-specific or immune cell-targeting drug discovery studies. 28836293 2 57 theme microvascular 357:369 arg1 proliferation 371:383 microvascular proliferation 357:383 microvascular proliferation 357:383 The key histological hallmarks of glioblastoma are pseudopalisading necrosis and microvascular proliferation, which allow pathologists to distinguish glioblastoma from lower-grade gliomas. 28836293 9 58 theme cell-specific 1688:1700 arg1 discovery 1732:1740 cancer cell-specific or immune cell-targeting drug discovery studies 1681:1748 discovery 1732:1740 These models can be generated in fully immunocompetent mixed or C57BL/6 genetic background mice, and therefore can easily be incorporated into preclinical studies for cancer cell-specific or immune cell-targeting drug discovery studies. 28836293 1 59 theme High-grade 115:124 arg1 glioblastomas 151:163 glioblastomas 151:163 glioblastomas 151:163 High-grade gliomas (HGG), including glioblastomas, are characterized by invasive growth, resistance to therapy, and high inter- and intra-tumoral heterogeneity. 28836293 1 59 theme High-grade 115:124 arg1 HGG 135:137 HGG 135:137 HGG 135:137 High-grade gliomas (HGG), including glioblastomas, are characterized by invasive growth, resistance to therapy, and high inter- and intra-tumoral heterogeneity. 28836293 1 59 theme High-grade 115:124 arg1 gliomas 126:132 High-grade gliomas 115:132 High-grade gliomas (HGG) 115:138 High-grade gliomas (HGG), including glioblastomas, are characterized by invasive growth, resistance to therapy, and high inter- and intra-tumoral heterogeneity. 28836293 5 60 dep microenvironmental 802:819 arg1 non-neoplastic 822:835 non-neoplastic 822:835 non-neoplastic 822:835 However, this question is of utmost importance since microenvironmental, non-neoplastic cells are key components of the most radiotherapy- and chemotherapy-resistant niches of the tumor. 28836293 8 61 theme murine 1311:1316 arg1 tumors 1318:1323 PDGFB-overexpressing and NF1-silenced murine tumors 1273:1323 PDGFB-overexpressing and NF1-silenced murine tumors 1273:1323 PDGFB-overexpressing and NF1-silenced murine tumors closely cluster with human proneural and mesenchymal subtypes, as well as PDGFRA-amplified and NF1-deleted/mutant human tumors, respectively, at both the RNA and protein expression levels. 28836293 7 62 from expression 1129:1138 arg1 microenvironment 1111:1126 tumor microenvironment 1105:1126 tumor microenvironment 1105:1126 This model shows significant differences in tumor microenvironment, expression of subtype-specific markers, and response to standard therapy when compared to our established PDGFB-overexpressing HGG mouse model. 28836293 8 63 theme PDGFRA-amplified 1399:1414 arg1 tumors 1445:1450 PDGFRA-amplified and NF1-deleted/mutant human tumors 1399:1450 PDGFRA-amplified and NF1-deleted/mutant human tumors 1399:1450 PDGFB-overexpressing and NF1-silenced murine tumors closely cluster with human proneural and mesenchymal subtypes, as well as PDGFRA-amplified and NF1-deleted/mutant human tumors, respectively, at both the RNA and protein expression levels. 28836293 3 64 dep heterogeneous 514:526 arg1 addition 468:475 addition 468:475 addition 468:475 In addition to being genetically and molecularly heterogeneous, HGG are also heterogeneous with respect to the composition of their microenvironment. 28836293 7 65 theme significant 1078:1088 arg1 differences 1090:1100 significant differences 1078:1100 significant differences in tumor microenvironment 1078:1126 This model shows significant differences in tumor microenvironment, expression of subtype-specific markers, and response to standard therapy when compared to our established PDGFB-overexpressing HGG mouse model. 28836293 9 66 dep discovery 1732:1740 arg1 studies 1742:1748 studies 1742:1748 studies 1742:1748 These models can be generated in fully immunocompetent mixed or C57BL/6 genetic background mice, and therefore can easily be incorporated into preclinical studies for cancer cell-specific or immune cell-targeting drug discovery studies. 28836293 8 67 theme mesenchymal 1366:1376 arg1 subtypes 1378:1385 human proneural and mesenchymal subtypes 1346:1385 human proneural and mesenchymal subtypes 1346:1385 PDGFB-overexpressing and NF1-silenced murine tumors closely cluster with human proneural and mesenchymal subtypes, as well as PDGFRA-amplified and NF1-deleted/mutant human tumors, respectively, at both the RNA and protein expression levels. 28836293 1 68 theme high 231:234 arg1 inter- 236:241 high inter- 231:241 high inter- 231:241 High-grade gliomas (HGG), including glioblastomas, are characterized by invasive growth, resistance to therapy, and high inter- and intra-tumoral heterogeneity. 28836293 0 69 theme microenvironmental 61:78 arg1 composition 80:90 microenvironmental composition 61:90 microenvironmental composition 61:90 Genetic driver mutations define the expression signature and microenvironmental composition of high-grade gliomas. 28836293 6 70 theme mouse 1008:1012 arg1 model 1014:1018 a versatile, reliable, and reproducible adult HGG mouse model 958:1018 a versatile, reliable, and reproducible adult HGG mouse model with NF1-silencing 958:1037 Our work demonstrates a versatile, reliable, and reproducible adult HGG mouse model with NF1-silencing as a driver mutation. 28836293 6 70 theme mouse 1008:1012 arg1 mutation 1051:1058 a driver mutation 1042:1058 a driver mutation 1042:1058 Our work demonstrates a versatile, reliable, and reproducible adult HGG mouse model with NF1-silencing as a driver mutation. 28836293 7 71 theme markers 1160:1166 arg1 expression 1129:1138 expression 1129:1138 expression of subtype-specific markers 1129:1166 This model shows significant differences in tumor microenvironment, expression of subtype-specific markers, and response to standard therapy when compared to our established PDGFB-overexpressing HGG mouse model. 28836293 7 71 theme markers 1160:1166 arg1 differences 1090:1100 significant differences 1078:1100 significant differences in tumor microenvironment 1078:1126 This model shows significant differences in tumor microenvironment, expression of subtype-specific markers, and response to standard therapy when compared to our established PDGFB-overexpressing HGG mouse model. 28836293 7 71 theme markers 1160:1166 arg1 response 1173:1180 response 1173:1180 response to standard therapy 1173:1200 This model shows significant differences in tumor microenvironment, expression of subtype-specific markers, and response to standard therapy when compared to our established PDGFB-overexpressing HGG mouse model. 28836293 9 72 theme preclinical 1657:1667 arg1 studies 1669:1675 preclinical studies 1657:1675 preclinical studies for cancer cell-specific or immune cell-targeting drug discovery studies 1657:1748 These models can be generated in fully immunocompetent mixed or C57BL/6 genetic background mice, and therefore can easily be incorporated into preclinical studies for cancer cell-specific or immune cell-targeting drug discovery studies. 28836293 5 73 theme microenvironmental 802:819 arg1 cells 837:841 microenvironmental, non-neoplastic cells 802:841 microenvironmental, non-neoplastic cells 802:841 However, this question is of utmost importance since microenvironmental, non-neoplastic cells are key components of the most radiotherapy- and chemotherapy-resistant niches of the tumor. 28836293 5 73 theme microenvironmental 802:819 arg1 components 851:860 key components 847:860 key components of the most radiotherapy- and chemotherapy-resistant niches of the tumor 847:933 However, this question is of utmost importance since microenvironmental, non-neoplastic cells are key components of the most radiotherapy- and chemotherapy-resistant niches of the tumor. 25682049 7 0 theme acidic 1502:1507 arg1 components 1524:1533 the acidic polysaccharide components 1498:1533 the acidic polysaccharide components (in terms of transparent exopolymer particles) 1498:1580 A large majority (>80%) of the acidic polysaccharide components (in terms of transparent exopolymer particles) were found in the colloidal size range (<0.4 μm). 25682049 4 1 theme Batch 902:906 arg1 monitoring 916:925 Batch culture monitoring 902:925 Batch culture monitoring of the three algal species 902:952 Batch culture monitoring of the three algal species illustrated varying characteristics in terms of growth pattern, cell concentration and AOM release. 25682049 5 2 theme other 1228:1232 arg1 acid 1255:1258 other low molecular weight acid and neutral compounds 1228:1280 acid 1255:1258 The AOM produced by the three algal species comprised mainly biopolymers (e.g., polysaccharides and proteins) but some refractory compounds (e.g., humic-like substances) and other low molecular weight acid and neutral compounds were also found. 25682049 7 3 from terms 1539:1543 arg1 majority 1479:1486 A large majority 1471:1486 A large majority (>80%) of the acidic polysaccharide components (in terms of transparent exopolymer particles) 1471:1580 A large majority (>80%) of the acidic polysaccharide components (in terms of transparent exopolymer particles) were found in the colloidal size range (<0.4 μm). 25682049 7 3 from terms 1539:1543 arg1 % 1492:1492 >80% 1489:1492 >80% 1489:1492 A large majority (>80%) of the acidic polysaccharide components (in terms of transparent exopolymer particles) were found in the colloidal size range (<0.4 μm). 25682049 8 4 theme relative 1636:1643 arg1 stickiness 1645:1654 The relative stickiness 1632:1654 The relative stickiness of AOM 1632:1661 The relative stickiness of AOM substantially varied between algal species and that the cohesion between AOM-coated surfaces was much stronger than the adhesion of AOM on AOM-free surfaces. 25682049 3 5 theme lectin 739:744 arg1 staining 746:753 lectin staining 739:753 lectin staining 739:753 were characterised employing various analytical techniques, such as liquid chromatography - organic carbon detection, fluorescence spectroscopy, fourier transform infrared spectroscopy, alcian blue staining and lectin staining coupled with laser scanning microscopy to indentify its composition and force measurement using atomic force microscopy to measure its stickiness. 25682049 5 6 theme molecular 1238:1246 arg1 acid 1255:1258 other low molecular weight acid and neutral compounds 1228:1280 acid 1255:1258 The AOM produced by the three algal species comprised mainly biopolymers (e.g., polysaccharides and proteins) but some refractory compounds (e.g., humic-like substances) and other low molecular weight acid and neutral compounds were also found. 25682049 1 7 theme low 183:185 arg1 pressure 187:194 low pressure 183:194 low pressure (micro- and ultra-filtration) 183:224 Algal blooms can seriously affect the operation of water treatment processes including low pressure (micro- and ultra-filtration) and high pressure (nanofiltration and reverse osmosis) membranes mainly due to accumulation of algal-derived organic matter (AOM). 25682049 7 8 from majority 1479:1486 arg1 terms 1539:1543 terms 1539:1543 terms of transparent exopolymer particles 1539:1579 A large majority (>80%) of the acidic polysaccharide components (in terms of transparent exopolymer particles) were found in the colloidal size range (<0.4 μm). 25682049 9 9 theme AOM 1916:1918 arg1 stickiness 1901:1910 stickiness 1901:1910 stickiness 1901:1910 Overall, the composition as well as the physico-chemical characteristics (e.g., stickiness) of AOM will likely dictate the severity of fouling in membrane systems during algal blooms. 25682049 9 9 theme AOM 1916:1918 arg1 composition 1834:1844 the composition 1830:1844 the composition as well as the physico-chemical characteristics (e.g., stickiness) of AOM 1830:1918 Overall, the composition as well as the physico-chemical characteristics (e.g., stickiness) of AOM will likely dictate the severity of fouling in membrane systems during algal blooms. 25682049 9 9 theme AOM 1916:1918 arg1 characteristics 1878:1892 the physico-chemical characteristics 1857:1892 the composition as well as the physico-chemical characteristics (e.g., stickiness) of AOM 1830:1918 Overall, the composition as well as the physico-chemical characteristics (e.g., stickiness) of AOM will likely dictate the severity of fouling in membrane systems during algal blooms. 25682049 3 10 theme laser 768:772 arg1 microscopy 783:792 laser scanning microscopy 768:792 laser scanning microscopy to indentify its composition 768:821 were characterised employing various analytical techniques, such as liquid chromatography - organic carbon detection, fluorescence spectroscopy, fourier transform infrared spectroscopy, alcian blue staining and lectin staining coupled with laser scanning microscopy to indentify its composition and force measurement using atomic force microscopy to measure its stickiness. 25682049 8 11 theme AOM-coated 1736:1745 arg1 surfaces 1747:1754 AOM-coated surfaces 1736:1754 AOM-coated surfaces 1736:1754 The relative stickiness of AOM substantially varied between algal species and that the cohesion between AOM-coated surfaces was much stronger than the adhesion of AOM on AOM-free surfaces. 25682049 3 12 theme various 557:563 arg1 techniques 576:585 various analytical techniques 557:585 various analytical techniques 557:585 were characterised employing various analytical techniques, such as liquid chromatography - organic carbon detection, fluorescence spectroscopy, fourier transform infrared spectroscopy, alcian blue staining and lectin staining coupled with laser scanning microscopy to indentify its composition and force measurement using atomic force microscopy to measure its stickiness. 25682049 3 13 dep fourier 673:679 arg1 transform 681:689 transform 681:689 transform infrared spectroscopy 681:711 were characterised employing various analytical techniques, such as liquid chromatography - organic carbon detection, fluorescence spectroscopy, fourier transform infrared spectroscopy, alcian blue staining and lectin staining coupled with laser scanning microscopy to indentify its composition and force measurement using atomic force microscopy to measure its stickiness. 25682049 3 14 dep transform 681:689 arg1 infrared 691:698 infrared 691:698 transform infrared spectroscopy 681:711 were characterised employing various analytical techniques, such as liquid chromatography - organic carbon detection, fluorescence spectroscopy, fourier transform infrared spectroscopy, alcian blue staining and lectin staining coupled with laser scanning microscopy to indentify its composition and force measurement using atomic force microscopy to measure its stickiness. 25682049 3 15 theme liquid 596:601 arg1 chromatography 603:616 liquid chromatography 596:616 liquid chromatography 596:616 were characterised employing various analytical techniques, such as liquid chromatography - organic carbon detection, fluorescence spectroscopy, fourier transform infrared spectroscopy, alcian blue staining and lectin staining coupled with laser scanning microscopy to indentify its composition and force measurement using atomic force microscopy to measure its stickiness. 25682049 6 16 theme functional 1343:1352 arg1 groups 1354:1359 sulphated functional groups 1333:1359 sulphated functional groups 1333:1359 Biopolymers containing fucose and sulphated functional groups were found in all AOM samples while the presence of other functional groups varied between different species. 25682049 9 17 dep stickiness 1901:1910 arg1 e.g. 1895:1898 e.g. 1895:1898 e.g. 1895:1898 Overall, the composition as well as the physico-chemical characteristics (e.g., stickiness) of AOM will likely dictate the severity of fouling in membrane systems during algal blooms. 25682049 4 18 theme algal 940:944 arg1 species 946:952 the three algal species 930:952 the three algal species 930:952 Batch culture monitoring of the three algal species illustrated varying characteristics in terms of growth pattern, cell concentration and AOM release. 25682049 3 19 theme force 827:831 arg1 measurement 833:843 force measurement 827:843 force measurement 827:843 were characterised employing various analytical techniques, such as liquid chromatography - organic carbon detection, fluorescence spectroscopy, fourier transform infrared spectroscopy, alcian blue staining and lectin staining coupled with laser scanning microscopy to indentify its composition and force measurement using atomic force microscopy to measure its stickiness. 25682049 5 20 theme algal 1084:1088 arg1 species 1090:1096 the three algal species 1074:1096 the three algal species 1074:1096 The AOM produced by the three algal species comprised mainly biopolymers (e.g., polysaccharides and proteins) but some refractory compounds (e.g., humic-like substances) and other low molecular weight acid and neutral compounds were also found. 25682049 3 21 theme carbon 628:633 arg1 detection 635:643 organic carbon detection 620:643 organic carbon detection 620:643 were characterised employing various analytical techniques, such as liquid chromatography - organic carbon detection, fluorescence spectroscopy, fourier transform infrared spectroscopy, alcian blue staining and lectin staining coupled with laser scanning microscopy to indentify its composition and force measurement using atomic force microscopy to measure its stickiness. 25682049 7 22 theme size 1610:1613 arg1 range 1615:1619 the colloidal size range 1596:1619 the colloidal size range (<0.4 μm) 1596:1629 A large majority (>80%) of the acidic polysaccharide components (in terms of transparent exopolymer particles) were found in the colloidal size range (<0.4 μm). 25682049 7 22 theme size 1610:1613 arg1 μm 1627:1628 <0.4 μm 1622:1628 <0.4 μm 1622:1628 A large majority (>80%) of the acidic polysaccharide components (in terms of transparent exopolymer particles) were found in the colloidal size range (<0.4 μm). 25682049 1 23 theme reverse 264:270 arg1 osmosis 272:278 reverse osmosis 264:278 reverse osmosis 264:278 Algal blooms can seriously affect the operation of water treatment processes including low pressure (micro- and ultra-filtration) and high pressure (nanofiltration and reverse osmosis) membranes mainly due to accumulation of algal-derived organic matter (AOM). 25682049 1 24 theme organic 335:341 arg1 AOM 351:353 AOM 351:353 AOM 351:353 Algal blooms can seriously affect the operation of water treatment processes including low pressure (micro- and ultra-filtration) and high pressure (nanofiltration and reverse osmosis) membranes mainly due to accumulation of algal-derived organic matter (AOM). 25682049 1 24 theme organic 335:341 arg1 matter 343:348 algal-derived organic matter 321:348 algal-derived organic matter (AOM) 321:354 Algal blooms can seriously affect the operation of water treatment processes including low pressure (micro- and ultra-filtration) and high pressure (nanofiltration and reverse osmosis) membranes mainly due to accumulation of algal-derived organic matter (AOM). 25682049 1 25 theme water 147:151 arg1 membranes 281:289 low pressure (micro- and ultra-filtration) and high pressure (nanofiltration and reverse osmosis) membranes 183:289 low pressure (micro- and ultra-filtration) and high pressure (nanofiltration and reverse osmosis) membranes 183:289 Algal blooms can seriously affect the operation of water treatment processes including low pressure (micro- and ultra-filtration) and high pressure (nanofiltration and reverse osmosis) membranes mainly due to accumulation of algal-derived organic matter (AOM). 25682049 1 25 theme water 147:151 arg1 processes 163:171 water treatment processes 147:171 water treatment processes including low pressure (micro- and ultra-filtration) and high pressure (nanofiltration and reverse osmosis) membranes 147:289 Algal blooms can seriously affect the operation of water treatment processes including low pressure (micro- and ultra-filtration) and high pressure (nanofiltration and reverse osmosis) membranes mainly due to accumulation of algal-derived organic matter (AOM). 25682049 4 26 theme concentration 1023:1035 arg1 terms 993:997 terms 993:997 terms of growth pattern, cell concentration and AOM release 993:1051 Batch culture monitoring of the three algal species illustrated varying characteristics in terms of growth pattern, cell concentration and AOM release. 25682049 9 27 theme algal 1991:1995 arg1 blooms 1997:2002 algal blooms 1991:2002 algal blooms 1991:2002 Overall, the composition as well as the physico-chemical characteristics (e.g., stickiness) of AOM will likely dictate the severity of fouling in membrane systems during algal blooms. 25682049 3 28 theme force 858:862 arg1 microscopy 864:873 atomic force microscopy 851:873 atomic force microscopy 851:873 were characterised employing various analytical techniques, such as liquid chromatography - organic carbon detection, fluorescence spectroscopy, fourier transform infrared spectroscopy, alcian blue staining and lectin staining coupled with laser scanning microscopy to indentify its composition and force measurement using atomic force microscopy to measure its stickiness. 25682049 0 29 theme freshwater 78:87 arg1 algae 89:93 bloom-forming marine and freshwater algae 53:93 algae 89:93 Characterisation of algal organic matter produced by bloom-forming marine and freshwater algae. 25682049 1 30 theme processes 163:171 arg1 operation 134:142 the operation 130:142 the operation of water treatment processes including low pressure (micro- and ultra-filtration) and high pressure (nanofiltration and reverse osmosis) membranes 130:289 Algal blooms can seriously affect the operation of water treatment processes including low pressure (micro- and ultra-filtration) and high pressure (nanofiltration and reverse osmosis) membranes mainly due to accumulation of algal-derived organic matter (AOM). 25682049 3 31 dep microscopy 783:792 arg1 indentify 797:805 indentify 797:805 to indentify its composition 794:821 were characterised employing various analytical techniques, such as liquid chromatography - organic carbon detection, fluorescence spectroscopy, fourier transform infrared spectroscopy, alcian blue staining and lectin staining coupled with laser scanning microscopy to indentify its composition and force measurement using atomic force microscopy to measure its stickiness. 25682049 4 32 theme growth 1002:1007 arg1 pattern 1009:1015 growth pattern 1002:1015 growth pattern 1002:1015 Batch culture monitoring of the three algal species illustrated varying characteristics in terms of growth pattern, cell concentration and AOM release. 25682049 2 33 theme different 376:384 arg1 components 386:395 the different components 372:395 the different components of AOM extracted from three common species of bloom-forming algae 372:461 In this study, the different components of AOM extracted from three common species of bloom-forming algae (Alexandrium tamarense, Chaetoceros affinis and Microcystis sp.) 25682049 6 34 theme AOM 1379:1381 arg1 samples 1383:1389 all AOM samples 1375:1389 all AOM samples 1375:1389 Biopolymers containing fucose and sulphated functional groups were found in all AOM samples while the presence of other functional groups varied between different species. 25682049 6 35 contain containing 1311:1320 arg2 fucose 1322:1327 fucose 1322:1327 fucose 1322:1327 Biopolymers containing fucose and sulphated functional groups were found in all AOM samples while the presence of other functional groups varied between different species. 25682049 6 35 contain containing 1311:1320 arg1 Biopolymers 1299:1309 Biopolymers 1299:1309 Biopolymers containing fucose 1299:1327 Biopolymers containing fucose and sulphated functional groups were found in all AOM samples while the presence of other functional groups varied between different species. 25682049 1 36 theme Algal 96:100 arg1 blooms 102:107 Algal blooms 96:107 Algal blooms 96:107 Algal blooms can seriously affect the operation of water treatment processes including low pressure (micro- and ultra-filtration) and high pressure (nanofiltration and reverse osmosis) membranes mainly due to accumulation of algal-derived organic matter (AOM). 25682049 0 37 theme algal 20:24 arg1 matter 34:39 algal organic matter 20:39 algal organic matter 20:39 Characterisation of algal organic matter produced by bloom-forming marine and freshwater algae. 25682049 7 38 theme transparent 1548:1558 arg1 particles 1571:1579 transparent exopolymer particles 1548:1579 transparent exopolymer particles 1548:1579 A large majority (>80%) of the acidic polysaccharide components (in terms of transparent exopolymer particles) were found in the colloidal size range (<0.4 μm). 25682049 4 39 theme AOM 1041:1043 arg1 release 1045:1051 AOM release 1041:1051 AOM release 1041:1051 Batch culture monitoring of the three algal species illustrated varying characteristics in terms of growth pattern, cell concentration and AOM release. 25682049 1 40 dep pressure 187:194 arg1 ultra-filtration 208:223 ultra-filtration 208:223 ultra-filtration 208:223 Algal blooms can seriously affect the operation of water treatment processes including low pressure (micro- and ultra-filtration) and high pressure (nanofiltration and reverse osmosis) membranes mainly due to accumulation of algal-derived organic matter (AOM). 25682049 1 40 dep pressure 187:194 arg1 micro- 197:202 micro- 197:202 micro- 197:202 Algal blooms can seriously affect the operation of water treatment processes including low pressure (micro- and ultra-filtration) and high pressure (nanofiltration and reverse osmosis) membranes mainly due to accumulation of algal-derived organic matter (AOM). 25682049 0 41 theme matter 34:39 arg1 Characterisation 0:15 Characterisation 0:15 Characterisation of algal organic matter 0:39 Characterisation of algal organic matter produced by bloom-forming marine and freshwater algae. 25682049 5 42 theme refractory 1173:1182 arg1 substances 1212:1221 humic-like substances 1201:1221 humic-like substances 1201:1221 The AOM produced by the three algal species comprised mainly biopolymers (e.g., polysaccharides and proteins) but some refractory compounds (e.g., humic-like substances) and other low molecular weight acid and neutral compounds were also found. 25682049 5 42 theme refractory 1173:1182 arg1 compounds 1184:1192 some refractory compounds 1168:1192 some refractory compounds (e.g., humic-like substances) 1168:1222 The AOM produced by the three algal species comprised mainly biopolymers (e.g., polysaccharides and proteins) but some refractory compounds (e.g., humic-like substances) and other low molecular weight acid and neutral compounds were also found. 25682049 2 43 theme bloom-forming 443:455 arg1 algae 457:461 bloom-forming algae 443:461 bloom-forming algae 443:461 In this study, the different components of AOM extracted from three common species of bloom-forming algae (Alexandrium tamarense, Chaetoceros affinis and Microcystis sp.) 25682049 6 44 theme other 1413:1417 arg1 groups 1430:1435 other functional groups 1413:1435 other functional groups 1413:1435 Biopolymers containing fucose and sulphated functional groups were found in all AOM samples while the presence of other functional groups varied between different species. 25682049 1 45 link algal-derived 321:333 arg1 AOM 351:353 AOM 351:353 AOM 351:353 Algal blooms can seriously affect the operation of water treatment processes including low pressure (micro- and ultra-filtration) and high pressure (nanofiltration and reverse osmosis) membranes mainly due to accumulation of algal-derived organic matter (AOM). 25682049 1 45 link algal-derived 321:333 arg1 matter 343:348 algal-derived organic matter 321:348 algal-derived organic matter (AOM) 321:354 Algal blooms can seriously affect the operation of water treatment processes including low pressure (micro- and ultra-filtration) and high pressure (nanofiltration and reverse osmosis) membranes mainly due to accumulation of algal-derived organic matter (AOM). 25682049 6 46 theme groups 1430:1435 arg1 presence 1401:1408 the presence 1397:1408 the presence of other functional groups 1397:1435 Biopolymers containing fucose and sulphated functional groups were found in all AOM samples while the presence of other functional groups varied between different species. 25682049 5 47 theme weight 1248:1253 arg1 acid 1255:1258 other low molecular weight acid and neutral compounds 1228:1280 acid 1255:1258 The AOM produced by the three algal species comprised mainly biopolymers (e.g., polysaccharides and proteins) but some refractory compounds (e.g., humic-like substances) and other low molecular weight acid and neutral compounds were also found. 25682049 7 48 theme polysaccharide 1509:1522 arg1 components 1524:1533 the acidic polysaccharide components 1498:1533 the acidic polysaccharide components (in terms of transparent exopolymer particles) 1498:1580 A large majority (>80%) of the acidic polysaccharide components (in terms of transparent exopolymer particles) were found in the colloidal size range (<0.4 μm). 25682049 3 49 dep such 588:591 arg1 as 593:594 as 593:594 as 593:594 were characterised employing various analytical techniques, such as liquid chromatography - organic carbon detection, fluorescence spectroscopy, fourier transform infrared spectroscopy, alcian blue staining and lectin staining coupled with laser scanning microscopy to indentify its composition and force measurement using atomic force microscopy to measure its stickiness. 25682049 1 50 theme pressure 235:242 arg1 membranes 281:289 low pressure (micro- and ultra-filtration) and high pressure (nanofiltration and reverse osmosis) membranes 183:289 low pressure (micro- and ultra-filtration) and high pressure (nanofiltration and reverse osmosis) membranes 183:289 Algal blooms can seriously affect the operation of water treatment processes including low pressure (micro- and ultra-filtration) and high pressure (nanofiltration and reverse osmosis) membranes mainly due to accumulation of algal-derived organic matter (AOM). 25682049 7 51 from components 1524:1533 arg1 terms 1539:1543 terms 1539:1543 terms of transparent exopolymer particles 1539:1579 A large majority (>80%) of the acidic polysaccharide components (in terms of transparent exopolymer particles) were found in the colloidal size range (<0.4 μm). 25682049 3 52 theme blue 721:724 arg1 staining 726:733 alcian blue staining 714:733 alcian blue staining 714:733 were characterised employing various analytical techniques, such as liquid chromatography - organic carbon detection, fluorescence spectroscopy, fourier transform infrared spectroscopy, alcian blue staining and lectin staining coupled with laser scanning microscopy to indentify its composition and force measurement using atomic force microscopy to measure its stickiness. 25682049 8 53 theme algal 1692:1696 arg1 species 1698:1704 algal species 1692:1704 algal species 1692:1704 The relative stickiness of AOM substantially varied between algal species and that the cohesion between AOM-coated surfaces was much stronger than the adhesion of AOM on AOM-free surfaces. 25682049 5 54 theme low 1234:1236 arg1 acid 1255:1258 other low molecular weight acid and neutral compounds 1228:1280 acid 1255:1258 The AOM produced by the three algal species comprised mainly biopolymers (e.g., polysaccharides and proteins) but some refractory compounds (e.g., humic-like substances) and other low molecular weight acid and neutral compounds were also found. 25682049 4 55 theme culture 908:914 arg1 monitoring 916:925 Batch culture monitoring 902:925 Batch culture monitoring of the three algal species 902:952 Batch culture monitoring of the three algal species illustrated varying characteristics in terms of growth pattern, cell concentration and AOM release. 25682049 7 56 theme large 1473:1477 arg1 majority 1479:1486 A large majority 1471:1486 A large majority (>80%) of the acidic polysaccharide components (in terms of transparent exopolymer particles) 1471:1580 A large majority (>80%) of the acidic polysaccharide components (in terms of transparent exopolymer particles) were found in the colloidal size range (<0.4 μm). 25682049 7 56 theme large 1473:1477 arg1 % 1492:1492 >80% 1489:1492 >80% 1489:1492 A large majority (>80%) of the acidic polysaccharide components (in terms of transparent exopolymer particles) were found in the colloidal size range (<0.4 μm). 25682049 3 57 theme analytical 565:574 arg1 techniques 576:585 various analytical techniques 557:585 various analytical techniques 557:585 were characterised employing various analytical techniques, such as liquid chromatography - organic carbon detection, fluorescence spectroscopy, fourier transform infrared spectroscopy, alcian blue staining and lectin staining coupled with laser scanning microscopy to indentify its composition and force measurement using atomic force microscopy to measure its stickiness. 25682049 1 58 theme pressure 187:194 arg1 membranes 281:289 low pressure (micro- and ultra-filtration) and high pressure (nanofiltration and reverse osmosis) membranes 183:289 low pressure (micro- and ultra-filtration) and high pressure (nanofiltration and reverse osmosis) membranes 183:289 Algal blooms can seriously affect the operation of water treatment processes including low pressure (micro- and ultra-filtration) and high pressure (nanofiltration and reverse osmosis) membranes mainly due to accumulation of algal-derived organic matter (AOM). 25682049 3 59 theme scanning 774:781 arg1 microscopy 783:792 laser scanning microscopy 768:792 laser scanning microscopy to indentify its composition 768:821 were characterised employing various analytical techniques, such as liquid chromatography - organic carbon detection, fluorescence spectroscopy, fourier transform infrared spectroscopy, alcian blue staining and lectin staining coupled with laser scanning microscopy to indentify its composition and force measurement using atomic force microscopy to measure its stickiness. 25682049 4 60 theme species 946:952 arg1 monitoring 916:925 Batch culture monitoring 902:925 Batch culture monitoring of the three algal species 902:952 Batch culture monitoring of the three algal species illustrated varying characteristics in terms of growth pattern, cell concentration and AOM release. 25682049 1 61 dep pressure 235:242 arg1 nanofiltration 245:258 nanofiltration 245:258 nanofiltration 245:258 Algal blooms can seriously affect the operation of water treatment processes including low pressure (micro- and ultra-filtration) and high pressure (nanofiltration and reverse osmosis) membranes mainly due to accumulation of algal-derived organic matter (AOM). 25682049 1 61 dep pressure 235:242 arg1 osmosis 272:278 reverse osmosis 264:278 reverse osmosis 264:278 Algal blooms can seriously affect the operation of water treatment processes including low pressure (micro- and ultra-filtration) and high pressure (nanofiltration and reverse osmosis) membranes mainly due to accumulation of algal-derived organic matter (AOM). 25682049 4 62 theme varying 966:972 arg1 characteristics 974:988 varying characteristics 966:988 varying characteristics 966:988 Batch culture monitoring of the three algal species illustrated varying characteristics in terms of growth pattern, cell concentration and AOM release. 25682049 8 63 from adhesion 1783:1790 arg1 surfaces 1811:1818 AOM-free surfaces 1802:1818 AOM-free surfaces 1802:1818 The relative stickiness of AOM substantially varied between algal species and that the cohesion between AOM-coated surfaces was much stronger than the adhesion of AOM on AOM-free surfaces. 25682049 9 64 theme fouling 1956:1962 arg1 severity 1944:1951 the severity 1940:1951 the severity of fouling in membrane systems 1940:1982 Overall, the composition as well as the physico-chemical characteristics (e.g., stickiness) of AOM will likely dictate the severity of fouling in membrane systems during algal blooms. 25682049 6 65 theme sulphated 1333:1341 arg1 groups 1354:1359 sulphated functional groups 1333:1359 sulphated functional groups 1333:1359 Biopolymers containing fucose and sulphated functional groups were found in all AOM samples while the presence of other functional groups varied between different species. 25682049 3 66 theme organic 620:626 arg1 detection 635:643 organic carbon detection 620:643 organic carbon detection 620:643 were characterised employing various analytical techniques, such as liquid chromatography - organic carbon detection, fluorescence spectroscopy, fourier transform infrared spectroscopy, alcian blue staining and lectin staining coupled with laser scanning microscopy to indentify its composition and force measurement using atomic force microscopy to measure its stickiness. 25682049 7 67 theme colloidal 1600:1608 arg1 range 1615:1619 the colloidal size range 1596:1619 the colloidal size range (<0.4 μm) 1596:1629 A large majority (>80%) of the acidic polysaccharide components (in terms of transparent exopolymer particles) were found in the colloidal size range (<0.4 μm). 25682049 7 67 theme colloidal 1600:1608 arg1 μm 1627:1628 <0.4 μm 1622:1628 <0.4 μm 1622:1628 A large majority (>80%) of the acidic polysaccharide components (in terms of transparent exopolymer particles) were found in the colloidal size range (<0.4 μm). 25682049 9 68 theme membrane 1967:1974 arg1 systems 1976:1982 membrane systems 1967:1982 membrane systems 1967:1982 Overall, the composition as well as the physico-chemical characteristics (e.g., stickiness) of AOM will likely dictate the severity of fouling in membrane systems during algal blooms. 25682049 6 69 theme functional 1419:1428 arg1 groups 1430:1435 other functional groups 1413:1435 other functional groups 1413:1435 Biopolymers containing fucose and sulphated functional groups were found in all AOM samples while the presence of other functional groups varied between different species. 25682049 4 70 theme pattern 1009:1015 arg1 terms 993:997 terms 993:997 terms of growth pattern, cell concentration and AOM release 993:1051 Batch culture monitoring of the three algal species illustrated varying characteristics in terms of growth pattern, cell concentration and AOM release. 25682049 5 71 dep substances 1212:1221 arg1 e.g. 1195:1198 e.g. 1195:1198 e.g. 1195:1198 The AOM produced by the three algal species comprised mainly biopolymers (e.g., polysaccharides and proteins) but some refractory compounds (e.g., humic-like substances) and other low molecular weight acid and neutral compounds were also found. 25682049 1 72 theme matter 343:348 arg1 accumulation 305:316 accumulation 305:316 accumulation of algal-derived organic matter (AOM) 305:354 Algal blooms can seriously affect the operation of water treatment processes including low pressure (micro- and ultra-filtration) and high pressure (nanofiltration and reverse osmosis) membranes mainly due to accumulation of algal-derived organic matter (AOM). 25682049 8 73 theme AOM 1795:1797 arg1 adhesion 1783:1790 the adhesion 1779:1790 the adhesion of AOM on AOM-free surfaces 1779:1818 The relative stickiness of AOM substantially varied between algal species and that the cohesion between AOM-coated surfaces was much stronger than the adhesion of AOM on AOM-free surfaces. 25682049 1 74 theme treatment 153:161 arg1 membranes 281:289 low pressure (micro- and ultra-filtration) and high pressure (nanofiltration and reverse osmosis) membranes 183:289 low pressure (micro- and ultra-filtration) and high pressure (nanofiltration and reverse osmosis) membranes 183:289 Algal blooms can seriously affect the operation of water treatment processes including low pressure (micro- and ultra-filtration) and high pressure (nanofiltration and reverse osmosis) membranes mainly due to accumulation of algal-derived organic matter (AOM). 25682049 1 74 theme treatment 153:161 arg1 processes 163:171 water treatment processes 147:171 water treatment processes including low pressure (micro- and ultra-filtration) and high pressure (nanofiltration and reverse osmosis) membranes 147:289 Algal blooms can seriously affect the operation of water treatment processes including low pressure (micro- and ultra-filtration) and high pressure (nanofiltration and reverse osmosis) membranes mainly due to accumulation of algal-derived organic matter (AOM). 25682049 4 75 theme cell 1018:1021 arg1 concentration 1023:1035 cell concentration 1018:1035 cell concentration 1018:1035 Batch culture monitoring of the three algal species illustrated varying characteristics in terms of growth pattern, cell concentration and AOM release. 25682049 8 76 theme AOM-free 1802:1809 arg1 surfaces 1811:1818 AOM-free surfaces 1802:1818 AOM-free surfaces 1802:1818 The relative stickiness of AOM substantially varied between algal species and that the cohesion between AOM-coated surfaces was much stronger than the adhesion of AOM on AOM-free surfaces. 25682049 6 77 located found 1366:1370 arg2 Biopolymers 1299:1309 Biopolymers 1299:1309 Biopolymers containing fucose 1299:1327 Biopolymers containing fucose and sulphated functional groups were found in all AOM samples while the presence of other functional groups varied between different species. 25682049 6 77 located found 1366:1370 arg2 groups 1354:1359 sulphated functional groups 1333:1359 sulphated functional groups 1333:1359 Biopolymers containing fucose and sulphated functional groups were found in all AOM samples while the presence of other functional groups varied between different species. 25682049 6 77 located found 1366:1370 arg1 samples 1383:1389 all AOM samples 1375:1389 all AOM samples 1375:1389 Biopolymers containing fucose and sulphated functional groups were found in all AOM samples while the presence of other functional groups varied between different species. 25682049 7 78 theme particles 1571:1579 arg1 terms 1539:1543 terms 1539:1543 terms of transparent exopolymer particles 1539:1579 A large majority (>80%) of the acidic polysaccharide components (in terms of transparent exopolymer particles) were found in the colloidal size range (<0.4 μm). 25682049 2 79 theme Microcystis 511:521 arg1 sp 523:524 Microcystis sp 511:524 Microcystis sp 511:524 In this study, the different components of AOM extracted from three common species of bloom-forming algae (Alexandrium tamarense, Chaetoceros affinis and Microcystis sp.) 25682049 3 80 theme atomic 851:856 arg1 microscopy 864:873 atomic force microscopy 851:873 atomic force microscopy 851:873 were characterised employing various analytical techniques, such as liquid chromatography - organic carbon detection, fluorescence spectroscopy, fourier transform infrared spectroscopy, alcian blue staining and lectin staining coupled with laser scanning microscopy to indentify its composition and force measurement using atomic force microscopy to measure its stickiness. 25682049 2 81 theme common 425:430 arg1 species 432:438 three common species 419:438 three common species of bloom-forming algae 419:461 In this study, the different components of AOM extracted from three common species of bloom-forming algae (Alexandrium tamarense, Chaetoceros affinis and Microcystis sp.) 25682049 0 82 theme organic 26:32 arg1 matter 34:39 algal organic matter 20:39 algal organic matter 20:39 Characterisation of algal organic matter produced by bloom-forming marine and freshwater algae. 25682049 5 83 theme humic-like 1201:1210 arg1 substances 1212:1221 humic-like substances 1201:1221 humic-like substances 1201:1221 The AOM produced by the three algal species comprised mainly biopolymers (e.g., polysaccharides and proteins) but some refractory compounds (e.g., humic-like substances) and other low molecular weight acid and neutral compounds were also found. 25682049 5 83 theme humic-like 1201:1210 arg1 compounds 1184:1192 some refractory compounds 1168:1192 some refractory compounds (e.g., humic-like substances) 1168:1222 The AOM produced by the three algal species comprised mainly biopolymers (e.g., polysaccharides and proteins) but some refractory compounds (e.g., humic-like substances) and other low molecular weight acid and neutral compounds were also found. 25682049 3 84 theme fluorescence 646:657 arg1 spectroscopy 659:670 fluorescence spectroscopy 646:670 fluorescence spectroscopy 646:670 were characterised employing various analytical techniques, such as liquid chromatography - organic carbon detection, fluorescence spectroscopy, fourier transform infrared spectroscopy, alcian blue staining and lectin staining coupled with laser scanning microscopy to indentify its composition and force measurement using atomic force microscopy to measure its stickiness. 25682049 2 85 theme AOM 400:402 arg1 components 386:395 the different components 372:395 the different components of AOM extracted from three common species of bloom-forming algae 372:461 In this study, the different components of AOM extracted from three common species of bloom-forming algae (Alexandrium tamarense, Chaetoceros affinis and Microcystis sp.) 25682049 6 86 theme different 1452:1460 arg1 species 1462:1468 different species 1452:1468 different species 1452:1468 Biopolymers containing fucose and sulphated functional groups were found in all AOM samples while the presence of other functional groups varied between different species. 25682049 7 87 theme exopolymer 1560:1569 arg1 particles 1571:1579 transparent exopolymer particles 1548:1579 transparent exopolymer particles 1548:1579 A large majority (>80%) of the acidic polysaccharide components (in terms of transparent exopolymer particles) were found in the colloidal size range (<0.4 μm). 25682049 7 88 located found 1587:1591 arg2 majority 1479:1486 A large majority 1471:1486 A large majority (>80%) of the acidic polysaccharide components (in terms of transparent exopolymer particles) 1471:1580 A large majority (>80%) of the acidic polysaccharide components (in terms of transparent exopolymer particles) were found in the colloidal size range (<0.4 μm). 25682049 7 88 located found 1587:1591 arg1 range 1615:1619 the colloidal size range 1596:1619 the colloidal size range (<0.4 μm) 1596:1629 A large majority (>80%) of the acidic polysaccharide components (in terms of transparent exopolymer particles) were found in the colloidal size range (<0.4 μm). 25682049 7 88 located found 1587:1591 arg1 μm 1627:1628 <0.4 μm 1622:1628 <0.4 μm 1622:1628 A large majority (>80%) of the acidic polysaccharide components (in terms of transparent exopolymer particles) were found in the colloidal size range (<0.4 μm). 25682049 7 88 located found 1587:1591 arg2 % 1492:1492 >80% 1489:1492 >80% 1489:1492 A large majority (>80%) of the acidic polysaccharide components (in terms of transparent exopolymer particles) were found in the colloidal size range (<0.4 μm). 25682049 8 89 theme AOM 1659:1661 arg1 stickiness 1645:1654 The relative stickiness 1632:1654 The relative stickiness of AOM 1632:1661 The relative stickiness of AOM substantially varied between algal species and that the cohesion between AOM-coated surfaces was much stronger than the adhesion of AOM on AOM-free surfaces. 25682049 9 90 from severity 1944:1951 arg1 systems 1976:1982 membrane systems 1967:1982 membrane systems 1967:1982 Overall, the composition as well as the physico-chemical characteristics (e.g., stickiness) of AOM will likely dictate the severity of fouling in membrane systems during algal blooms. 25682049 2 91 theme algae 457:461 arg1 species 432:438 three common species 419:438 three common species of bloom-forming algae 419:461 In this study, the different components of AOM extracted from three common species of bloom-forming algae (Alexandrium tamarense, Chaetoceros affinis and Microcystis sp.) 25682049 5 92 dep polysaccharides 1134:1148 arg1 e.g. 1128:1131 e.g. 1128:1131 e.g. 1128:1131 The AOM produced by the three algal species comprised mainly biopolymers (e.g., polysaccharides and proteins) but some refractory compounds (e.g., humic-like substances) and other low molecular weight acid and neutral compounds were also found. 25682049 2 93 dep components 386:395 arg1 study 365:369 this study 360:369 this study 360:369 In this study, the different components of AOM extracted from three common species of bloom-forming algae (Alexandrium tamarense, Chaetoceros affinis and Microcystis sp.) 25682049 2 93 dep components 386:395 arg1 Chaetoceros 487:497 Chaetoceros 487:497 Chaetoceros 487:497 In this study, the different components of AOM extracted from three common species of bloom-forming algae (Alexandrium tamarense, Chaetoceros affinis and Microcystis sp.) 25682049 0 94 theme bloom-forming 53:65 arg1 marine 67:72 bloom-forming marine and freshwater algae 53:93 marine 67:72 Characterisation of algal organic matter produced by bloom-forming marine and freshwater algae. 25682049 4 95 theme release 1045:1051 arg1 terms 993:997 terms 993:997 terms of growth pattern, cell concentration and AOM release 993:1051 Batch culture monitoring of the three algal species illustrated varying characteristics in terms of growth pattern, cell concentration and AOM release. 25682049 1 96 theme algal-derived 321:333 arg1 AOM 351:353 AOM 351:353 AOM 351:353 Algal blooms can seriously affect the operation of water treatment processes including low pressure (micro- and ultra-filtration) and high pressure (nanofiltration and reverse osmosis) membranes mainly due to accumulation of algal-derived organic matter (AOM). 25682049 1 96 theme algal-derived 321:333 arg1 matter 343:348 algal-derived organic matter 321:348 algal-derived organic matter (AOM) 321:354 Algal blooms can seriously affect the operation of water treatment processes including low pressure (micro- and ultra-filtration) and high pressure (nanofiltration and reverse osmosis) membranes mainly due to accumulation of algal-derived organic matter (AOM). 25682049 2 97 dep Chaetoceros 487:497 arg1 affinis 499:505 affinis 499:505 affinis 499:505 In this study, the different components of AOM extracted from three common species of bloom-forming algae (Alexandrium tamarense, Chaetoceros affinis and Microcystis sp.) 25682049 2 97 dep Chaetoceros 487:497 arg1 sp 523:524 Microcystis sp 511:524 Microcystis sp 511:524 In this study, the different components of AOM extracted from three common species of bloom-forming algae (Alexandrium tamarense, Chaetoceros affinis and Microcystis sp.) 25682049 5 98 dep biopolymers 1115:1125 arg1 polysaccharides 1134:1148 polysaccharides 1134:1148 polysaccharides 1134:1148 The AOM produced by the three algal species comprised mainly biopolymers (e.g., polysaccharides and proteins) but some refractory compounds (e.g., humic-like substances) and other low molecular weight acid and neutral compounds were also found. 25682049 5 98 dep biopolymers 1115:1125 arg1 proteins 1154:1161 proteins 1154:1161 proteins 1154:1161 The AOM produced by the three algal species comprised mainly biopolymers (e.g., polysaccharides and proteins) but some refractory compounds (e.g., humic-like substances) and other low molecular weight acid and neutral compounds were also found. 25682049 1 99 theme high 230:233 arg1 pressure 235:242 high pressure 230:242 high pressure (nanofiltration and reverse osmosis) 230:279 Algal blooms can seriously affect the operation of water treatment processes including low pressure (micro- and ultra-filtration) and high pressure (nanofiltration and reverse osmosis) membranes mainly due to accumulation of algal-derived organic matter (AOM). 25682049 7 100 theme components 1524:1533 arg1 majority 1479:1486 A large majority 1471:1486 A large majority (>80%) of the acidic polysaccharide components (in terms of transparent exopolymer particles) 1471:1580 A large majority (>80%) of the acidic polysaccharide components (in terms of transparent exopolymer particles) were found in the colloidal size range (<0.4 μm). 25682049 7 100 theme components 1524:1533 arg1 % 1492:1492 >80% 1489:1492 >80% 1489:1492 A large majority (>80%) of the acidic polysaccharide components (in terms of transparent exopolymer particles) were found in the colloidal size range (<0.4 μm). 25682049 9 101 theme physico-chemical 1861:1876 arg1 stickiness 1901:1910 stickiness 1901:1910 stickiness 1901:1910 Overall, the composition as well as the physico-chemical characteristics (e.g., stickiness) of AOM will likely dictate the severity of fouling in membrane systems during algal blooms. 25682049 9 101 theme physico-chemical 1861:1876 arg1 characteristics 1878:1892 the physico-chemical characteristics 1857:1892 the composition as well as the physico-chemical characteristics (e.g., stickiness) of AOM 1830:1918 Overall, the composition as well as the physico-chemical characteristics (e.g., stickiness) of AOM will likely dictate the severity of fouling in membrane systems during algal blooms. 25682049 3 102 theme alcian 714:719 arg1 staining 726:733 alcian blue staining 714:733 alcian blue staining 714:733 were characterised employing various analytical techniques, such as liquid chromatography - organic carbon detection, fluorescence spectroscopy, fourier transform infrared spectroscopy, alcian blue staining and lectin staining coupled with laser scanning microscopy to indentify its composition and force measurement using atomic force microscopy to measure its stickiness. 25682049 5 103 theme neutral 1264:1270 arg1 compounds 1272:1280 other low molecular weight acid and neutral compounds 1228:1280 compounds 1272:1280 The AOM produced by the three algal species comprised mainly biopolymers (e.g., polysaccharides and proteins) but some refractory compounds (e.g., humic-like substances) and other low molecular weight acid and neutral compounds were also found. 28987372 1 0 theme classic 310:316 arg1 TCM 348:350 TCM 348:350 TCM 348:350 Bai-Hu-Tang (BHT), a classic traditional Chinese medicine (TCM) formula used for clearing heat and promoting body fluid, consists of four traditional Chinese medicines, i.e., Gypsum Fibrosum (Shigao), Anemarrhenae Rhizoma (Zhimu), Glycyrrhizae Radix et Rhizoma Praeparata cum Melle (Zhigancao), and nonglutinous rice (Jingmi). 28987372 1 0 theme classic 310:316 arg1 medicine 338:345 a classic traditional Chinese medicine 308:345 a classic traditional Chinese medicine (TCM) formula used for clearing heat and promoting body fluid 308:407 Bai-Hu-Tang (BHT), a classic traditional Chinese medicine (TCM) formula used for clearing heat and promoting body fluid, consists of four traditional Chinese medicines, i.e., Gypsum Fibrosum (Shigao), Anemarrhenae Rhizoma (Zhimu), Glycyrrhizae Radix et Rhizoma Praeparata cum Melle (Zhigancao), and nonglutinous rice (Jingmi). 28987372 3 1 theme secondary 737:745 arg1 metabolites 747:757 secondary metabolites 737:757 secondary metabolites 737:757 To qualitatively and quantitatively characterize secondary metabolites and carbohydrates in BHT, here a combination of analytical approaches using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and ultraperformance liquid chromatography coupled with photodiode array detector was developed and validated. 28987372 1 2 theme Chinese 330:336 arg1 TCM 348:350 TCM 348:350 TCM 348:350 Bai-Hu-Tang (BHT), a classic traditional Chinese medicine (TCM) formula used for clearing heat and promoting body fluid, consists of four traditional Chinese medicines, i.e., Gypsum Fibrosum (Shigao), Anemarrhenae Rhizoma (Zhimu), Glycyrrhizae Radix et Rhizoma Praeparata cum Melle (Zhigancao), and nonglutinous rice (Jingmi). 28987372 1 2 theme Chinese 330:336 arg1 medicine 338:345 a classic traditional Chinese medicine 308:345 a classic traditional Chinese medicine (TCM) formula used for clearing heat and promoting body fluid 308:407 Bai-Hu-Tang (BHT), a classic traditional Chinese medicine (TCM) formula used for clearing heat and promoting body fluid, consists of four traditional Chinese medicines, i.e., Gypsum Fibrosum (Shigao), Anemarrhenae Rhizoma (Zhimu), Glycyrrhizae Radix et Rhizoma Praeparata cum Melle (Zhigancao), and nonglutinous rice (Jingmi). 28987372 7 3 from metabolites 1831:1841 arg1 medicine 1884:1891 traditional Chinese medicine 1864:1891 traditional Chinese medicine 1864:1891 The research deliverables not only laid the root for further chemical and biological evaluation of BHT, but also provided a comprehensive analytical strategy for chemical characterization of secondary metabolites and carbohydrates in traditional Chinese medicine formulas. 28987372 5 4 from oligosaccharides 1275:1290 arg1 BHT 1316:1318 BHT 1316:1318 BHT 1316:1318 Meanwhile, polysaccharides, oligosaccharides, and monosaccharides in BHT were also characterized via sample pretreatment followed by sugar composition analysis. 28987372 7 5 from carbohydrates 1847:1859 arg1 medicine 1884:1891 traditional Chinese medicine 1864:1891 traditional Chinese medicine 1864:1891 The research deliverables not only laid the root for further chemical and biological evaluation of BHT, but also provided a comprehensive analytical strategy for chemical characterization of secondary metabolites and carbohydrates in traditional Chinese medicine formulas. 28987372 4 6 theme quadrupole 1202:1211 arg1 spectrometry 1233:1244 quadrupole time-of-flight mass spectrometry 1202:1244 quadrupole time-of-flight mass spectrometry 1202:1244 A total of 42 secondary metabolites in BHT were tentatively or definitely identified, of which 10 major chemicals were quantified by the extracting ion mode of quadrupole time-of-flight mass spectrometry. 28987372 5 7 from polysaccharides 1258:1272 arg1 BHT 1316:1318 BHT 1316:1318 BHT 1316:1318 Meanwhile, polysaccharides, oligosaccharides, and monosaccharides in BHT were also characterized via sample pretreatment followed by sugar composition analysis. 28987372 6 8 theme BHT 1625:1627 arg1 dissection 1591:1600 chemical dissection 1582:1600 chemical dissection 1582:1600 The quantitative results indicated that the determined chemicals accounted for 35.76% of the total extract of BHT, which demonstrated that the study could be instrumental in chemical dissection and quality control of BHT. 28987372 6 8 theme BHT 1625:1627 arg1 control 1614:1620 quality control 1606:1620 quality control of BHT 1606:1627 The quantitative results indicated that the determined chemicals accounted for 35.76% of the total extract of BHT, which demonstrated that the study could be instrumental in chemical dissection and quality control of BHT. 28987372 3 9 from metabolites 747:757 arg1 BHT 780:782 BHT 780:782 BHT 780:782 To qualitatively and quantitatively characterize secondary metabolites and carbohydrates in BHT, here a combination of analytical approaches using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and ultraperformance liquid chromatography coupled with photodiode array detector was developed and validated. 28987372 4 10 theme extracting 1179:1188 arg1 mode 1194:1197 the extracting ion mode 1175:1197 the extracting ion mode of quadrupole time-of-flight mass spectrometry 1175:1244 A total of 42 secondary metabolites in BHT were tentatively or definitely identified, of which 10 major chemicals were quantified by the extracting ion mode of quadrupole time-of-flight mass spectrometry. 28987372 7 11 theme traditional 1864:1874 arg1 medicine 1884:1891 traditional Chinese medicine 1864:1891 traditional Chinese medicine 1864:1891 The research deliverables not only laid the root for further chemical and biological evaluation of BHT, but also provided a comprehensive analytical strategy for chemical characterization of secondary metabolites and carbohydrates in traditional Chinese medicine formulas. 28987372 0 12 theme time-of-flight 173:186 arg1 spectrometry 193:204 quadrupole time-of-flight mass spectrometry 162:204 quadrupole time-of-flight mass spectrometry 162:204 Qualitative and quantitative characterization of secondary metabolites and carbohydrates in Bai-Hu-Tang using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and ultraperformance liquid chromatography coupled with photodiode array detector. 28987372 1 13 theme Chinese 439:445 arg1 Shigao 481:486 Shigao 481:486 Shigao 481:486 Bai-Hu-Tang (BHT), a classic traditional Chinese medicine (TCM) formula used for clearing heat and promoting body fluid, consists of four traditional Chinese medicines, i.e., Gypsum Fibrosum (Shigao), Anemarrhenae Rhizoma (Zhimu), Glycyrrhizae Radix et Rhizoma Praeparata cum Melle (Zhigancao), and nonglutinous rice (Jingmi). 28987372 1 13 theme Chinese 439:445 arg1 Zhigancao 572:580 Zhigancao 572:580 Zhigancao 572:580 Bai-Hu-Tang (BHT), a classic traditional Chinese medicine (TCM) formula used for clearing heat and promoting body fluid, consists of four traditional Chinese medicines, i.e., Gypsum Fibrosum (Shigao), Anemarrhenae Rhizoma (Zhimu), Glycyrrhizae Radix et Rhizoma Praeparata cum Melle (Zhigancao), and nonglutinous rice (Jingmi). 28987372 1 13 theme Chinese 439:445 arg1 rice 601:604 nonglutinous rice 588:604 nonglutinous rice 588:604 Bai-Hu-Tang (BHT), a classic traditional Chinese medicine (TCM) formula used for clearing heat and promoting body fluid, consists of four traditional Chinese medicines, i.e., Gypsum Fibrosum (Shigao), Anemarrhenae Rhizoma (Zhimu), Glycyrrhizae Radix et Rhizoma Praeparata cum Melle (Zhigancao), and nonglutinous rice (Jingmi). 28987372 1 13 theme Chinese 439:445 arg1 medicines 447:455 four traditional Chinese medicines 422:455 four traditional Chinese medicines 422:455 Bai-Hu-Tang (BHT), a classic traditional Chinese medicine (TCM) formula used for clearing heat and promoting body fluid, consists of four traditional Chinese medicines, i.e., Gypsum Fibrosum (Shigao), Anemarrhenae Rhizoma (Zhimu), Glycyrrhizae Radix et Rhizoma Praeparata cum Melle (Zhigancao), and nonglutinous rice (Jingmi). 28987372 1 13 theme Chinese 439:445 arg1 Rhizoma 503:509 Rhizoma 503:509 Rhizoma 503:509 Bai-Hu-Tang (BHT), a classic traditional Chinese medicine (TCM) formula used for clearing heat and promoting body fluid, consists of four traditional Chinese medicines, i.e., Gypsum Fibrosum (Shigao), Anemarrhenae Rhizoma (Zhimu), Glycyrrhizae Radix et Rhizoma Praeparata cum Melle (Zhigancao), and nonglutinous rice (Jingmi). 28987372 6 14 theme quantitative 1412:1423 arg1 results 1425:1431 The quantitative results 1408:1431 The quantitative results 1408:1431 The quantitative results indicated that the determined chemicals accounted for 35.76% of the total extract of BHT, which demonstrated that the study could be instrumental in chemical dissection and quality control of BHT. 28987372 3 15 theme time-of-flight 898:911 arg1 spectrometry 918:929 quadrupole time-of-flight mass spectrometry 887:929 quadrupole time-of-flight mass spectrometry 887:929 To qualitatively and quantitatively characterize secondary metabolites and carbohydrates in BHT, here a combination of analytical approaches using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and ultraperformance liquid chromatography coupled with photodiode array detector was developed and validated. 28987372 7 16 theme biological 1704:1713 arg1 evaluation 1715:1724 further chemical and biological evaluation 1683:1724 further chemical and biological evaluation of BHT 1683:1731 The research deliverables not only laid the root for further chemical and biological evaluation of BHT, but also provided a comprehensive analytical strategy for chemical characterization of secondary metabolites and carbohydrates in traditional Chinese medicine formulas. 28987372 5 17 theme sugar 1380:1384 arg1 analysis 1398:1405 sugar composition analysis 1380:1405 sugar composition analysis 1380:1405 Meanwhile, polysaccharides, oligosaccharides, and monosaccharides in BHT were also characterized via sample pretreatment followed by sugar composition analysis. 28987372 3 18 theme approaches 818:827 arg1 combination 792:802 a combination 790:802 a combination of analytical approaches using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and ultraperformance liquid chromatography coupled with photodiode array detector 790:1011 To qualitatively and quantitatively characterize secondary metabolites and carbohydrates in BHT, here a combination of analytical approaches using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and ultraperformance liquid chromatography coupled with photodiode array detector was developed and validated. 28987372 0 19 theme ultraperformance 210:225 arg1 chromatography 234:247 ultraperformance liquid chromatography 210:247 ultraperformance liquid chromatography 210:247 Qualitative and quantitative characterization of secondary metabolites and carbohydrates in Bai-Hu-Tang using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and ultraperformance liquid chromatography coupled with photodiode array detector. 28987372 7 20 theme carbohydrates 1847:1859 arg1 characterization 1801:1816 chemical characterization 1792:1816 chemical characterization of secondary metabolites and carbohydrates in traditional Chinese medicine formulas 1792:1900 The research deliverables not only laid the root for further chemical and biological evaluation of BHT, but also provided a comprehensive analytical strategy for chemical characterization of secondary metabolites and carbohydrates in traditional Chinese medicine formulas. 28987372 7 21 theme chemical 1691:1698 arg1 evaluation 1715:1724 further chemical and biological evaluation 1683:1724 further chemical and biological evaluation of BHT 1683:1731 The research deliverables not only laid the root for further chemical and biological evaluation of BHT, but also provided a comprehensive analytical strategy for chemical characterization of secondary metabolites and carbohydrates in traditional Chinese medicine formulas. 28987372 4 22 theme mass 1228:1231 arg1 spectrometry 1233:1244 quadrupole time-of-flight mass spectrometry 1202:1244 quadrupole time-of-flight mass spectrometry 1202:1244 A total of 42 secondary metabolites in BHT were tentatively or definitely identified, of which 10 major chemicals were quantified by the extracting ion mode of quadrupole time-of-flight mass spectrometry. 28987372 3 23 theme mass 913:916 arg1 spectrometry 918:929 quadrupole time-of-flight mass spectrometry 887:929 quadrupole time-of-flight mass spectrometry 887:929 To qualitatively and quantitatively characterize secondary metabolites and carbohydrates in BHT, here a combination of analytical approaches using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and ultraperformance liquid chromatography coupled with photodiode array detector was developed and validated. 28987372 0 24 theme carbohydrates 75:87 arg1 characterization 29:44 Qualitative and quantitative characterization 0:44 Qualitative and quantitative characterization of secondary metabolites and carbohydrates in Bai-Hu-Tang 0:102 Qualitative and quantitative characterization of secondary metabolites and carbohydrates in Bai-Hu-Tang using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and ultraperformance liquid chromatography coupled with photodiode array detector. 28987372 7 25 theme metabolites 1831:1841 arg1 characterization 1801:1816 chemical characterization 1792:1816 chemical characterization of secondary metabolites and carbohydrates in traditional Chinese medicine formulas 1792:1900 The research deliverables not only laid the root for further chemical and biological evaluation of BHT, but also provided a comprehensive analytical strategy for chemical characterization of secondary metabolites and carbohydrates in traditional Chinese medicine formulas. 28987372 4 26 theme secondary 1056:1064 arg1 metabolites 1066:1076 42 secondary metabolites 1053:1076 42 secondary metabolites in BHT 1053:1083 A total of 42 secondary metabolites in BHT were tentatively or definitely identified, of which 10 major chemicals were quantified by the extracting ion mode of quadrupole time-of-flight mass spectrometry. 28987372 5 27 theme sample 1348:1353 arg1 pretreatment 1355:1366 sample pretreatment 1348:1366 sample pretreatment followed by sugar composition analysis 1348:1405 Meanwhile, polysaccharides, oligosaccharides, and monosaccharides in BHT were also characterized via sample pretreatment followed by sugar composition analysis. 28987372 3 28 theme ultraperformance 835:850 arg1 chromatography 859:872 ultraperformance liquid chromatography 835:872 ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and ultraperformance liquid chromatography coupled with photodiode array detector 835:1011 To qualitatively and quantitatively characterize secondary metabolites and carbohydrates in BHT, here a combination of analytical approaches using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and ultraperformance liquid chromatography coupled with photodiode array detector was developed and validated. 28987372 0 29 theme ultraperformance 110:125 arg1 chromatography 134:147 ultraperformance liquid chromatography 110:147 ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and ultraperformance liquid chromatography coupled with photodiode array detector 110:286 Qualitative and quantitative characterization of secondary metabolites and carbohydrates in Bai-Hu-Tang using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and ultraperformance liquid chromatography coupled with photodiode array detector. 28987372 7 30 theme chemical 1792:1799 arg1 characterization 1801:1816 chemical characterization 1792:1816 chemical characterization of secondary metabolites and carbohydrates in traditional Chinese medicine formulas 1792:1900 The research deliverables not only laid the root for further chemical and biological evaluation of BHT, but also provided a comprehensive analytical strategy for chemical characterization of secondary metabolites and carbohydrates in traditional Chinese medicine formulas. 28987372 0 31 theme Qualitative 0:10 arg1 characterization 29:44 Qualitative and quantitative characterization 0:44 Qualitative and quantitative characterization of secondary metabolites and carbohydrates in Bai-Hu-Tang 0:102 Qualitative and quantitative characterization of secondary metabolites and carbohydrates in Bai-Hu-Tang using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and ultraperformance liquid chromatography coupled with photodiode array detector. 28987372 1 32 theme medicine 338:345 arg1 formula 353:359 a classic traditional Chinese medicine (TCM) formula 308:359 a classic traditional Chinese medicine (TCM) formula used for clearing heat and promoting body fluid 308:407 Bai-Hu-Tang (BHT), a classic traditional Chinese medicine (TCM) formula used for clearing heat and promoting body fluid, consists of four traditional Chinese medicines, i.e., Gypsum Fibrosum (Shigao), Anemarrhenae Rhizoma (Zhimu), Glycyrrhizae Radix et Rhizoma Praeparata cum Melle (Zhigancao), and nonglutinous rice (Jingmi). 28987372 1 32 theme medicine 338:345 arg1 Bai-Hu-Tang 289:299 Bai-Hu-Tang 289:299 Bai-Hu-Tang (BHT) 289:305 Bai-Hu-Tang (BHT), a classic traditional Chinese medicine (TCM) formula used for clearing heat and promoting body fluid, consists of four traditional Chinese medicines, i.e., Gypsum Fibrosum (Shigao), Anemarrhenae Rhizoma (Zhimu), Glycyrrhizae Radix et Rhizoma Praeparata cum Melle (Zhigancao), and nonglutinous rice (Jingmi). 28987372 7 33 theme comprehensive 1754:1766 arg1 strategy 1779:1786 a comprehensive analytical strategy 1752:1786 a comprehensive analytical strategy for chemical characterization of secondary metabolites and carbohydrates in traditional Chinese medicine formulas 1752:1900 The research deliverables not only laid the root for further chemical and biological evaluation of BHT, but also provided a comprehensive analytical strategy for chemical characterization of secondary metabolites and carbohydrates in traditional Chinese medicine formulas. 28987372 0 34 theme quantitative 16:27 arg1 characterization 29:44 Qualitative and quantitative characterization 0:44 Qualitative and quantitative characterization of secondary metabolites and carbohydrates in Bai-Hu-Tang 0:102 Qualitative and quantitative characterization of secondary metabolites and carbohydrates in Bai-Hu-Tang using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and ultraperformance liquid chromatography coupled with photodiode array detector. 28987372 3 35 theme array 998:1002 arg1 detector 1004:1011 photodiode array detector 987:1011 photodiode array detector 987:1011 To qualitatively and quantitatively characterize secondary metabolites and carbohydrates in BHT, here a combination of analytical approaches using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and ultraperformance liquid chromatography coupled with photodiode array detector was developed and validated. 28987372 1 36 theme nonglutinous 588:599 arg1 rice 601:604 nonglutinous rice 588:604 nonglutinous rice 588:604 Bai-Hu-Tang (BHT), a classic traditional Chinese medicine (TCM) formula used for clearing heat and promoting body fluid, consists of four traditional Chinese medicines, i.e., Gypsum Fibrosum (Shigao), Anemarrhenae Rhizoma (Zhimu), Glycyrrhizae Radix et Rhizoma Praeparata cum Melle (Zhigancao), and nonglutinous rice (Jingmi). 28987372 1 36 theme nonglutinous 588:599 arg1 medicines 447:455 four traditional Chinese medicines 422:455 four traditional Chinese medicines 422:455 Bai-Hu-Tang (BHT), a classic traditional Chinese medicine (TCM) formula used for clearing heat and promoting body fluid, consists of four traditional Chinese medicines, i.e., Gypsum Fibrosum (Shigao), Anemarrhenae Rhizoma (Zhimu), Glycyrrhizae Radix et Rhizoma Praeparata cum Melle (Zhigancao), and nonglutinous rice (Jingmi). 28987372 6 37 theme BHT 1518:1520 arg1 extract 1507:1513 the total extract 1497:1513 the total extract of BHT 1497:1520 The quantitative results indicated that the determined chemicals accounted for 35.76% of the total extract of BHT, which demonstrated that the study could be instrumental in chemical dissection and quality control of BHT. 28987372 0 38 theme metabolites 59:69 arg1 characterization 29:44 Qualitative and quantitative characterization 0:44 Qualitative and quantitative characterization of secondary metabolites and carbohydrates in Bai-Hu-Tang 0:102 Qualitative and quantitative characterization of secondary metabolites and carbohydrates in Bai-Hu-Tang using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and ultraperformance liquid chromatography coupled with photodiode array detector. 28987372 0 39 theme array 273:277 arg1 detector 279:286 photodiode array detector 262:286 photodiode array detector 262:286 Qualitative and quantitative characterization of secondary metabolites and carbohydrates in Bai-Hu-Tang using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and ultraperformance liquid chromatography coupled with photodiode array detector. 28987372 1 40 dep medicines 447:455 arg1 i.e. 458:461 four traditional Chinese medicines, i.e., Gypsum Fibrosum (Shigao), Anemarrhenae Rhizoma (Zhimu), Glycyrrhizae Radix et Rhizoma Praeparata cum Melle (Zhigancao), and nonglutinous rice (Jingmi) 422:613 i.e. 458:461 Bai-Hu-Tang (BHT), a classic traditional Chinese medicine (TCM) formula used for clearing heat and promoting body fluid, consists of four traditional Chinese medicines, i.e., Gypsum Fibrosum (Shigao), Anemarrhenae Rhizoma (Zhimu), Glycyrrhizae Radix et Rhizoma Praeparata cum Melle (Zhigancao), and nonglutinous rice (Jingmi). 28987372 3 41 theme ultraperformance 935:950 arg1 chromatography 959:972 ultraperformance liquid chromatography 935:972 ultraperformance liquid chromatography 935:972 To qualitatively and quantitatively characterize secondary metabolites and carbohydrates in BHT, here a combination of analytical approaches using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and ultraperformance liquid chromatography coupled with photodiode array detector was developed and validated. 28987372 0 42 theme photodiode 262:271 arg1 array 273:277 photodiode array 262:277 photodiode array detector 262:286 Qualitative and quantitative characterization of secondary metabolites and carbohydrates in Bai-Hu-Tang using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and ultraperformance liquid chromatography coupled with photodiode array detector. 28987372 1 43 theme traditional 318:328 arg1 TCM 348:350 TCM 348:350 TCM 348:350 Bai-Hu-Tang (BHT), a classic traditional Chinese medicine (TCM) formula used for clearing heat and promoting body fluid, consists of four traditional Chinese medicines, i.e., Gypsum Fibrosum (Shigao), Anemarrhenae Rhizoma (Zhimu), Glycyrrhizae Radix et Rhizoma Praeparata cum Melle (Zhigancao), and nonglutinous rice (Jingmi). 28987372 1 43 theme traditional 318:328 arg1 medicine 338:345 a classic traditional Chinese medicine 308:345 a classic traditional Chinese medicine (TCM) formula used for clearing heat and promoting body fluid 308:407 Bai-Hu-Tang (BHT), a classic traditional Chinese medicine (TCM) formula used for clearing heat and promoting body fluid, consists of four traditional Chinese medicines, i.e., Gypsum Fibrosum (Shigao), Anemarrhenae Rhizoma (Zhimu), Glycyrrhizae Radix et Rhizoma Praeparata cum Melle (Zhigancao), and nonglutinous rice (Jingmi). 28987372 5 44 from monosaccharides 1297:1311 arg1 BHT 1316:1318 BHT 1316:1318 BHT 1316:1318 Meanwhile, polysaccharides, oligosaccharides, and monosaccharides in BHT were also characterized via sample pretreatment followed by sugar composition analysis. 28987372 6 45 theme extract 1507:1513 arg1 extract 1507:1513 the total extract 1497:1513 the total extract of BHT 1497:1520 The quantitative results indicated that the determined chemicals accounted for 35.76% of the total extract of BHT, which demonstrated that the study could be instrumental in chemical dissection and quality control of BHT. 28987372 6 45 theme extract 1507:1513 arg1 % 1492:1492 35.76% 1487:1492 35.76% 1487:1492 The quantitative results indicated that the determined chemicals accounted for 35.76% of the total extract of BHT, which demonstrated that the study could be instrumental in chemical dissection and quality control of BHT. 28987372 2 46 theme chemical 620:627 arg1 composition 629:639 The chemical composition 616:639 The chemical composition of BHT 616:646 The chemical composition of BHT still remains largely elusive thus far. 28987372 4 47 theme time-of-flight 1213:1226 arg1 spectrometry 1233:1244 quadrupole time-of-flight mass spectrometry 1202:1244 quadrupole time-of-flight mass spectrometry 1202:1244 A total of 42 secondary metabolites in BHT were tentatively or definitely identified, of which 10 major chemicals were quantified by the extracting ion mode of quadrupole time-of-flight mass spectrometry. 28987372 0 48 theme quadrupole 162:171 arg1 spectrometry 193:204 quadrupole time-of-flight mass spectrometry 162:204 quadrupole time-of-flight mass spectrometry 162:204 Qualitative and quantitative characterization of secondary metabolites and carbohydrates in Bai-Hu-Tang using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and ultraperformance liquid chromatography coupled with photodiode array detector. 28987372 6 49 from dissection 1591:1600 arg1 study 1551:1555 the study 1547:1555 the study 1547:1555 The quantitative results indicated that the determined chemicals accounted for 35.76% of the total extract of BHT, which demonstrated that the study could be instrumental in chemical dissection and quality control of BHT. 28987372 6 49 from dissection 1591:1600 arg1 instrumental 1566:1577 instrumental 1566:1577 instrumental 1566:1577 The quantitative results indicated that the determined chemicals accounted for 35.76% of the total extract of BHT, which demonstrated that the study could be instrumental in chemical dissection and quality control of BHT. 28987372 7 50 theme BHT 1729:1731 arg1 evaluation 1715:1724 further chemical and biological evaluation 1683:1724 further chemical and biological evaluation of BHT 1683:1731 The research deliverables not only laid the root for further chemical and biological evaluation of BHT, but also provided a comprehensive analytical strategy for chemical characterization of secondary metabolites and carbohydrates in traditional Chinese medicine formulas. 28987372 4 51 theme ion 1190:1192 arg1 mode 1194:1197 the extracting ion mode 1175:1197 the extracting ion mode of quadrupole time-of-flight mass spectrometry 1175:1244 A total of 42 secondary metabolites in BHT were tentatively or definitely identified, of which 10 major chemicals were quantified by the extracting ion mode of quadrupole time-of-flight mass spectrometry. 28987372 0 52 theme mass 188:191 arg1 spectrometry 193:204 quadrupole time-of-flight mass spectrometry 162:204 quadrupole time-of-flight mass spectrometry 162:204 Qualitative and quantitative characterization of secondary metabolites and carbohydrates in Bai-Hu-Tang using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and ultraperformance liquid chromatography coupled with photodiode array detector. 28987372 1 53 theme traditional 427:437 arg1 Shigao 481:486 Shigao 481:486 Shigao 481:486 Bai-Hu-Tang (BHT), a classic traditional Chinese medicine (TCM) formula used for clearing heat and promoting body fluid, consists of four traditional Chinese medicines, i.e., Gypsum Fibrosum (Shigao), Anemarrhenae Rhizoma (Zhimu), Glycyrrhizae Radix et Rhizoma Praeparata cum Melle (Zhigancao), and nonglutinous rice (Jingmi). 28987372 1 53 theme traditional 427:437 arg1 Zhigancao 572:580 Zhigancao 572:580 Zhigancao 572:580 Bai-Hu-Tang (BHT), a classic traditional Chinese medicine (TCM) formula used for clearing heat and promoting body fluid, consists of four traditional Chinese medicines, i.e., Gypsum Fibrosum (Shigao), Anemarrhenae Rhizoma (Zhimu), Glycyrrhizae Radix et Rhizoma Praeparata cum Melle (Zhigancao), and nonglutinous rice (Jingmi). 28987372 1 53 theme traditional 427:437 arg1 rice 601:604 nonglutinous rice 588:604 nonglutinous rice 588:604 Bai-Hu-Tang (BHT), a classic traditional Chinese medicine (TCM) formula used for clearing heat and promoting body fluid, consists of four traditional Chinese medicines, i.e., Gypsum Fibrosum (Shigao), Anemarrhenae Rhizoma (Zhimu), Glycyrrhizae Radix et Rhizoma Praeparata cum Melle (Zhigancao), and nonglutinous rice (Jingmi). 28987372 1 53 theme traditional 427:437 arg1 medicines 447:455 four traditional Chinese medicines 422:455 four traditional Chinese medicines 422:455 Bai-Hu-Tang (BHT), a classic traditional Chinese medicine (TCM) formula used for clearing heat and promoting body fluid, consists of four traditional Chinese medicines, i.e., Gypsum Fibrosum (Shigao), Anemarrhenae Rhizoma (Zhimu), Glycyrrhizae Radix et Rhizoma Praeparata cum Melle (Zhigancao), and nonglutinous rice (Jingmi). 28987372 1 53 theme traditional 427:437 arg1 Rhizoma 503:509 Rhizoma 503:509 Rhizoma 503:509 Bai-Hu-Tang (BHT), a classic traditional Chinese medicine (TCM) formula used for clearing heat and promoting body fluid, consists of four traditional Chinese medicines, i.e., Gypsum Fibrosum (Shigao), Anemarrhenae Rhizoma (Zhimu), Glycyrrhizae Radix et Rhizoma Praeparata cum Melle (Zhigancao), and nonglutinous rice (Jingmi). 28987372 6 54 theme quality 1606:1612 arg1 control 1614:1620 quality control 1606:1620 quality control of BHT 1606:1627 The quantitative results indicated that the determined chemicals accounted for 35.76% of the total extract of BHT, which demonstrated that the study could be instrumental in chemical dissection and quality control of BHT. 28987372 1 55 theme clearing 370:377 arg1 heat 379:382 clearing heat 370:382 clearing heat 370:382 Bai-Hu-Tang (BHT), a classic traditional Chinese medicine (TCM) formula used for clearing heat and promoting body fluid, consists of four traditional Chinese medicines, i.e., Gypsum Fibrosum (Shigao), Anemarrhenae Rhizoma (Zhimu), Glycyrrhizae Radix et Rhizoma Praeparata cum Melle (Zhigancao), and nonglutinous rice (Jingmi). 28987372 6 56 theme determined 1452:1461 arg1 chemicals 1463:1471 the determined chemicals 1448:1471 the determined chemicals 1448:1471 The quantitative results indicated that the determined chemicals accounted for 35.76% of the total extract of BHT, which demonstrated that the study could be instrumental in chemical dissection and quality control of BHT. 28987372 0 57 theme liquid 227:232 arg1 chromatography 234:247 ultraperformance liquid chromatography 210:247 ultraperformance liquid chromatography 210:247 Qualitative and quantitative characterization of secondary metabolites and carbohydrates in Bai-Hu-Tang using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and ultraperformance liquid chromatography coupled with photodiode array detector. 28987372 7 58 theme Chinese 1876:1882 arg1 medicine 1884:1891 traditional Chinese medicine 1864:1891 traditional Chinese medicine 1864:1891 The research deliverables not only laid the root for further chemical and biological evaluation of BHT, but also provided a comprehensive analytical strategy for chemical characterization of secondary metabolites and carbohydrates in traditional Chinese medicine formulas. 28987372 7 59 theme further 1683:1689 arg1 evaluation 1715:1724 further chemical and biological evaluation 1683:1724 further chemical and biological evaluation of BHT 1683:1731 The research deliverables not only laid the root for further chemical and biological evaluation of BHT, but also provided a comprehensive analytical strategy for chemical characterization of secondary metabolites and carbohydrates in traditional Chinese medicine formulas. 28987372 4 60 theme spectrometry 1233:1244 arg1 mode 1194:1197 the extracting ion mode 1175:1197 the extracting ion mode of quadrupole time-of-flight mass spectrometry 1175:1244 A total of 42 secondary metabolites in BHT were tentatively or definitely identified, of which 10 major chemicals were quantified by the extracting ion mode of quadrupole time-of-flight mass spectrometry. 28987372 5 61 theme composition 1386:1396 arg1 analysis 1398:1405 sugar composition analysis 1380:1405 sugar composition analysis 1380:1405 Meanwhile, polysaccharides, oligosaccharides, and monosaccharides in BHT were also characterized via sample pretreatment followed by sugar composition analysis. 28987372 6 62 theme total 1501:1505 arg1 extract 1507:1513 the total extract 1497:1513 the total extract of BHT 1497:1520 The quantitative results indicated that the determined chemicals accounted for 35.76% of the total extract of BHT, which demonstrated that the study could be instrumental in chemical dissection and quality control of BHT. 28987372 3 63 theme quadrupole 887:896 arg1 spectrometry 918:929 quadrupole time-of-flight mass spectrometry 887:929 quadrupole time-of-flight mass spectrometry 887:929 To qualitatively and quantitatively characterize secondary metabolites and carbohydrates in BHT, here a combination of analytical approaches using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and ultraperformance liquid chromatography coupled with photodiode array detector was developed and validated. 28987372 0 64 from characterization 29:44 arg1 Bai-Hu-Tang 92:102 Bai-Hu-Tang 92:102 Bai-Hu-Tang 92:102 Qualitative and quantitative characterization of secondary metabolites and carbohydrates in Bai-Hu-Tang using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and ultraperformance liquid chromatography coupled with photodiode array detector. 28987372 7 65 from characterization 1801:1816 arg1 medicine 1884:1891 traditional Chinese medicine 1864:1891 traditional Chinese medicine 1864:1891 The research deliverables not only laid the root for further chemical and biological evaluation of BHT, but also provided a comprehensive analytical strategy for chemical characterization of secondary metabolites and carbohydrates in traditional Chinese medicine formulas. 28987372 3 66 theme analytical 807:816 arg1 approaches 818:827 analytical approaches 807:827 analytical approaches using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and ultraperformance liquid chromatography coupled with photodiode array detector 807:1011 To qualitatively and quantitatively characterize secondary metabolites and carbohydrates in BHT, here a combination of analytical approaches using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and ultraperformance liquid chromatography coupled with photodiode array detector was developed and validated. 28987372 3 67 theme liquid 952:957 arg1 chromatography 959:972 ultraperformance liquid chromatography 935:972 ultraperformance liquid chromatography 935:972 To qualitatively and quantitatively characterize secondary metabolites and carbohydrates in BHT, here a combination of analytical approaches using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and ultraperformance liquid chromatography coupled with photodiode array detector was developed and validated. 28987372 0 68 theme liquid 127:132 arg1 chromatography 134:147 ultraperformance liquid chromatography 110:147 ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and ultraperformance liquid chromatography coupled with photodiode array detector 110:286 Qualitative and quantitative characterization of secondary metabolites and carbohydrates in Bai-Hu-Tang using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and ultraperformance liquid chromatography coupled with photodiode array detector. 28987372 1 69 theme body 398:401 arg1 fluid 403:407 body fluid 398:407 body fluid 398:407 Bai-Hu-Tang (BHT), a classic traditional Chinese medicine (TCM) formula used for clearing heat and promoting body fluid, consists of four traditional Chinese medicines, i.e., Gypsum Fibrosum (Shigao), Anemarrhenae Rhizoma (Zhimu), Glycyrrhizae Radix et Rhizoma Praeparata cum Melle (Zhigancao), and nonglutinous rice (Jingmi). 28987372 7 70 theme secondary 1821:1829 arg1 metabolites 1831:1841 secondary metabolites 1821:1841 secondary metabolites 1821:1841 The research deliverables not only laid the root for further chemical and biological evaluation of BHT, but also provided a comprehensive analytical strategy for chemical characterization of secondary metabolites and carbohydrates in traditional Chinese medicine formulas. 28987372 2 71 theme BHT 644:646 arg1 composition 629:639 The chemical composition 616:639 The chemical composition of BHT 616:646 The chemical composition of BHT still remains largely elusive thus far. 28987372 3 72 theme liquid 852:857 arg1 chromatography 859:872 ultraperformance liquid chromatography 835:872 ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and ultraperformance liquid chromatography coupled with photodiode array detector 835:1011 To qualitatively and quantitatively characterize secondary metabolites and carbohydrates in BHT, here a combination of analytical approaches using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and ultraperformance liquid chromatography coupled with photodiode array detector was developed and validated. 28987372 1 73 dep Glycyrrhizae 520:531 arg1 et 539:540 Glycyrrhizae Radix et 520:540 Glycyrrhizae Radix et Rhizoma Praeparata cum Melle (Zhigancao) 520:581 Bai-Hu-Tang (BHT), a classic traditional Chinese medicine (TCM) formula used for clearing heat and promoting body fluid, consists of four traditional Chinese medicines, i.e., Gypsum Fibrosum (Shigao), Anemarrhenae Rhizoma (Zhimu), Glycyrrhizae Radix et Rhizoma Praeparata cum Melle (Zhigancao), and nonglutinous rice (Jingmi). 28987372 1 74 dep formula 353:359 arg1 promoting 388:396 promoting 388:396 promoting body fluid 388:407 Bai-Hu-Tang (BHT), a classic traditional Chinese medicine (TCM) formula used for clearing heat and promoting body fluid, consists of four traditional Chinese medicines, i.e., Gypsum Fibrosum (Shigao), Anemarrhenae Rhizoma (Zhimu), Glycyrrhizae Radix et Rhizoma Praeparata cum Melle (Zhigancao), and nonglutinous rice (Jingmi). 28987372 1 74 dep formula 353:359 arg1 used 361:364 used 361:364 used for clearing heat 361:382 Bai-Hu-Tang (BHT), a classic traditional Chinese medicine (TCM) formula used for clearing heat and promoting body fluid, consists of four traditional Chinese medicines, i.e., Gypsum Fibrosum (Shigao), Anemarrhenae Rhizoma (Zhimu), Glycyrrhizae Radix et Rhizoma Praeparata cum Melle (Zhigancao), and nonglutinous rice (Jingmi). 28987372 3 75 from carbohydrates 763:775 arg1 BHT 780:782 BHT 780:782 BHT 780:782 To qualitatively and quantitatively characterize secondary metabolites and carbohydrates in BHT, here a combination of analytical approaches using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and ultraperformance liquid chromatography coupled with photodiode array detector was developed and validated. 28987372 6 76 from control 1614:1620 arg1 study 1551:1555 the study 1547:1555 the study 1547:1555 The quantitative results indicated that the determined chemicals accounted for 35.76% of the total extract of BHT, which demonstrated that the study could be instrumental in chemical dissection and quality control of BHT. 28987372 6 76 from control 1614:1620 arg1 instrumental 1566:1577 instrumental 1566:1577 instrumental 1566:1577 The quantitative results indicated that the determined chemicals accounted for 35.76% of the total extract of BHT, which demonstrated that the study could be instrumental in chemical dissection and quality control of BHT. 28987372 7 77 dep metabolites 1831:1841 arg1 formulas 1893:1900 formulas 1893:1900 formulas 1893:1900 The research deliverables not only laid the root for further chemical and biological evaluation of BHT, but also provided a comprehensive analytical strategy for chemical characterization of secondary metabolites and carbohydrates in traditional Chinese medicine formulas. 28987372 7 78 theme analytical 1768:1777 arg1 strategy 1779:1786 a comprehensive analytical strategy 1752:1786 a comprehensive analytical strategy for chemical characterization of secondary metabolites and carbohydrates in traditional Chinese medicine formulas 1752:1900 The research deliverables not only laid the root for further chemical and biological evaluation of BHT, but also provided a comprehensive analytical strategy for chemical characterization of secondary metabolites and carbohydrates in traditional Chinese medicine formulas. 28987372 0 79 theme secondary 49:57 arg1 metabolites 59:69 secondary metabolites 49:69 secondary metabolites 49:69 Qualitative and quantitative characterization of secondary metabolites and carbohydrates in Bai-Hu-Tang using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and ultraperformance liquid chromatography coupled with photodiode array detector. 28987372 3 80 theme photodiode 987:996 arg1 array 998:1002 photodiode array 987:1002 photodiode array detector 987:1011 To qualitatively and quantitatively characterize secondary metabolites and carbohydrates in BHT, here a combination of analytical approaches using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and ultraperformance liquid chromatography coupled with photodiode array detector was developed and validated. 28987372 4 81 theme metabolites 1066:1076 arg1 total 1044:1048 A total 1042:1048 A total of 42 secondary metabolites in BHT 1042:1083 A total of 42 secondary metabolites in BHT were tentatively or definitely identified, of which 10 major chemicals were quantified by the extracting ion mode of quadrupole time-of-flight mass spectrometry. 28987372 4 82 from BHT 1081:1083 arg1 total 1044:1048 A total 1042:1048 A total of 42 secondary metabolites in BHT 1042:1083 A total of 42 secondary metabolites in BHT were tentatively or definitely identified, of which 10 major chemicals were quantified by the extracting ion mode of quadrupole time-of-flight mass spectrometry. 28987372 7 83 from medicine 1884:1891 arg1 characterization 1801:1816 chemical characterization 1792:1816 chemical characterization of secondary metabolites and carbohydrates in traditional Chinese medicine formulas 1792:1900 The research deliverables not only laid the root for further chemical and biological evaluation of BHT, but also provided a comprehensive analytical strategy for chemical characterization of secondary metabolites and carbohydrates in traditional Chinese medicine formulas. 28987372 4 84 from metabolites 1066:1076 arg1 BHT 1081:1083 BHT 1081:1083 BHT 1081:1083 A total of 42 secondary metabolites in BHT were tentatively or definitely identified, of which 10 major chemicals were quantified by the extracting ion mode of quadrupole time-of-flight mass spectrometry. 28987372 4 85 theme major 1140:1144 arg1 chemicals 1146:1154 10 major chemicals 1137:1154 10 major chemicals 1137:1154 A total of 42 secondary metabolites in BHT were tentatively or definitely identified, of which 10 major chemicals were quantified by the extracting ion mode of quadrupole time-of-flight mass spectrometry. 28987372 6 86 theme chemical 1582:1589 arg1 dissection 1591:1600 chemical dissection 1582:1600 chemical dissection 1582:1600 The quantitative results indicated that the determined chemicals accounted for 35.76% of the total extract of BHT, which demonstrated that the study could be instrumental in chemical dissection and quality control of BHT. 28987372 6 87 from instrumental 1566:1577 arg1 dissection 1591:1600 chemical dissection 1582:1600 chemical dissection 1582:1600 The quantitative results indicated that the determined chemicals accounted for 35.76% of the total extract of BHT, which demonstrated that the study could be instrumental in chemical dissection and quality control of BHT. 28987372 6 87 from instrumental 1566:1577 arg1 control 1614:1620 quality control 1606:1620 quality control of BHT 1606:1627 The quantitative results indicated that the determined chemicals accounted for 35.76% of the total extract of BHT, which demonstrated that the study could be instrumental in chemical dissection and quality control of BHT. 28987372 7 88 dep deliverables 1643:1654 arg1 laid 1665:1668 laid 1665:1668 laid the root for further chemical and biological evaluation of BHT 1665:1731 The research deliverables not only laid the root for further chemical and biological evaluation of BHT, but also provided a comprehensive analytical strategy for chemical characterization of secondary metabolites and carbohydrates in traditional Chinese medicine formulas. 28987372 7 88 dep deliverables 1643:1654 arg1 provided 1743:1750 provided 1743:1750 provided a comprehensive analytical strategy for chemical characterization of secondary metabolites and carbohydrates in traditional Chinese medicine formulas 1743:1900 The research deliverables not only laid the root for further chemical and biological evaluation of BHT, but also provided a comprehensive analytical strategy for chemical characterization of secondary metabolites and carbohydrates in traditional Chinese medicine formulas. 28987372 4 89 from total 1044:1048 arg1 BHT 1081:1083 BHT 1081:1083 BHT 1081:1083 A total of 42 secondary metabolites in BHT were tentatively or definitely identified, of which 10 major chemicals were quantified by the extracting ion mode of quadrupole time-of-flight mass spectrometry. 26285173 6 0 theme time-dependent 1030:1043 arg1 manner 1045:1050 a time-dependent manner 1028:1050 a time-dependent manner 1028:1050 In addition, 2-DG (1.0mM) significantly inhibited mRNA and protein expression of vascular endothelial growth receptor 2 (VEGFR2) in a time-dependent manner. 26285173 3 1 theme 2-DG 499:502 arg1 action 489:494 the anti-angiogenic action 469:494 the anti-angiogenic action of 2-DG 469:502 MAIN METHODS We first employed an ex vivo rat aortic ring model to substantiate the anti-angiogenic action of 2-DG and then used HUVECs to investigate the molecular mechanism underlying such an action. 26285173 10 2 link N-linked 1679:1686 arg1 glycosylation 1688:1700 N-linked glycosylation 1679:1700 N-linked glycosylation of VEGFR2 1679:1710 SIGNIFICANCE This ex vivo and in vitro study demonstrates that 2-DG inhibits angiogenesis with an action involving attenuation of VEGFR2 signaling and MMP-2 expression, possibly resulting from interference with N-linked glycosylation of VEGFR2. 26285173 10 3 theme N-linked 1679:1686 arg1 glycosylation 1688:1700 N-linked glycosylation 1679:1700 N-linked glycosylation of VEGFR2 1679:1710 SIGNIFICANCE This ex vivo and in vitro study demonstrates that 2-DG inhibits angiogenesis with an action involving attenuation of VEGFR2 signaling and MMP-2 expression, possibly resulting from interference with N-linked glycosylation of VEGFR2. 26285173 10 4 theme in 1498:1499 arg1 study 1507:1511 This ex vivo and in vitro study 1481:1511 This ex vivo and in vitro study 1481:1511 SIGNIFICANCE This ex vivo and in vitro study demonstrates that 2-DG inhibits angiogenesis with an action involving attenuation of VEGFR2 signaling and MMP-2 expression, possibly resulting from interference with N-linked glycosylation of VEGFR2. 26285173 10 5 theme VEGFR2 1705:1710 arg1 glycosylation 1688:1700 N-linked glycosylation 1679:1700 N-linked glycosylation of VEGFR2 1679:1710 SIGNIFICANCE This ex vivo and in vitro study demonstrates that 2-DG inhibits angiogenesis with an action involving attenuation of VEGFR2 signaling and MMP-2 expression, possibly resulting from interference with N-linked glycosylation of VEGFR2. 26285173 5 6 theme protein 830:836 arg1 expression 838:847 mRNA and protein expression 821:847 expression 838:847 2-DG (0.1-1.0mM) also significantly inhibited cell invasion and migration, as well as the activity and mRNA and protein expression of matrix metalloproteinase (MMP)-2 in HUVECs. 26285173 4 7 theme tube 666:669 arg1 formation 671:679 tube formation 666:679 tube formation 666:679 KEY FINDINGS Results reveal that 2-DG (0.05-1.0mM) significantly inhibited tube formation in both rat aortic rings and HUVECs. 26285173 10 8 dep in 1498:1499 arg1 vitro 1501:1505 vitro 1501:1505 vitro 1501:1505 SIGNIFICANCE This ex vivo and in vitro study demonstrates that 2-DG inhibits angiogenesis with an action involving attenuation of VEGFR2 signaling and MMP-2 expression, possibly resulting from interference with N-linked glycosylation of VEGFR2. 26285173 3 9 theme molecular 544:552 arg1 mechanism 554:562 the molecular mechanism 540:562 the molecular mechanism underlying such an action 540:588 MAIN METHODS We first employed an ex vivo rat aortic ring model to substantiate the anti-angiogenic action of 2-DG and then used HUVECs to investigate the molecular mechanism underlying such an action. 26285173 8 10 theme glycosylation 1355:1367 arg1 precursor 1369:1377 an N-linked glycosylation precursor 1343:1377 an N-linked glycosylation precursor 1343:1377 The effects of 2-DG on tube formation, MMP-2 activity, and VEGFR2 protein expression in HUVECs were reversed by mannose, an N-linked glycosylation precursor. 26285173 8 10 theme glycosylation 1355:1367 arg1 mannose 1334:1340 mannose 1334:1340 mannose 1334:1340 The effects of 2-DG on tube formation, MMP-2 activity, and VEGFR2 protein expression in HUVECs were reversed by mannose, an N-linked glycosylation precursor. 26285173 5 11 theme mRNA 821:824 arg1 expression 838:847 mRNA and protein expression 821:847 expression 838:847 2-DG (0.1-1.0mM) also significantly inhibited cell invasion and migration, as well as the activity and mRNA and protein expression of matrix metalloproteinase (MMP)-2 in HUVECs. 26285173 9 12 theme VEGFR2 1431:1436 arg1 accumulation 1415:1426 2-DG-induced accumulation 1402:1426 2-DG-induced accumulation of VEGFR2 in the endoplasmic reticulum 1402:1465 Mannose also reversed 2-DG-induced accumulation of VEGFR2 in the endoplasmic reticulum. 26285173 8 13 theme 2-DG 1237:1240 arg1 effects 1226:1232 The effects 1222:1232 The effects of 2-DG on tube formation, MMP-2 activity, and VEGFR2 protein expression in HUVECs 1222:1315 The effects of 2-DG on tube formation, MMP-2 activity, and VEGFR2 protein expression in HUVECs were reversed by mannose, an N-linked glycosylation precursor. 26285173 11 14 theme Further 1713:1719 arg1 studies 1721:1727 Further studies 1713:1727 Further studies 1713:1727 Further studies are needed to show that 2-DG inhibits VEGF-mediated angiogenesis or that the actual status of N-glycosylation of VEGFR2 is affected by the treatment. 26285173 1 15 gly glycosylation 300:312 arg1 interference 273:284 interference 273:284 interference with N-linked glycosylation 273:312 AIMS 2-Deoxyglucose (2-DG) is a glucose analogue and has been shown to inhibit angiogenesis in human umbilical vascular endothelial cells (HUVECs) through interference with N-linked glycosylation. 26285173 5 16 from expression 838:847 arg1 HUVECs 888:893 HUVECs 888:893 HUVECs 888:893 2-DG (0.1-1.0mM) also significantly inhibited cell invasion and migration, as well as the activity and mRNA and protein expression of matrix metalloproteinase (MMP)-2 in HUVECs. 26285173 10 17 dep SIGNIFICANCE 1468:1479 arg1 demonstrates 1513:1524 demonstrates 1513:1524 demonstrates that 2-DG inhibits angiogenesis with an action involving attenuation of VEGFR2 signaling and MMP-2 expression, possibly resulting from interference with N-linked glycosylation of VEGFR2 1513:1710 SIGNIFICANCE This ex vivo and in vitro study demonstrates that 2-DG inhibits angiogenesis with an action involving attenuation of VEGFR2 signaling and MMP-2 expression, possibly resulting from interference with N-linked glycosylation of VEGFR2. 26285173 0 18 from expression 96:105 arg1 HUVECs 110:115 HUVECs 110:115 HUVECs 110:115 The anti-angiogenic action of 2-deoxyglucose involves attenuation of VEGFR2 signaling and MMP-2 expression in HUVECs. 26285173 8 19 theme tube 1245:1248 arg1 formation 1250:1258 tube formation 1245:1258 tube formation 1245:1258 The effects of 2-DG on tube formation, MMP-2 activity, and VEGFR2 protein expression in HUVECs were reversed by mannose, an N-linked glycosylation precursor. 26285173 0 20 theme VEGFR2 69:74 arg1 signaling 76:84 VEGFR2 signaling 69:84 VEGFR2 signaling 69:84 The anti-angiogenic action of 2-deoxyglucose involves attenuation of VEGFR2 signaling and MMP-2 expression in HUVECs. 26285173 10 21 gly glycosylation 1688:1700 arg1 VEGFR2 1705:1710 VEGFR2 1705:1710 VEGFR2 1705:1710 SIGNIFICANCE This ex vivo and in vitro study demonstrates that 2-DG inhibits angiogenesis with an action involving attenuation of VEGFR2 signaling and MMP-2 expression, possibly resulting from interference with N-linked glycosylation of VEGFR2. 26285173 10 21 gly glycosylation 1688:1700 arg1 interference 1661:1672 interference 1661:1672 interference with N-linked glycosylation of VEGFR2 1661:1710 SIGNIFICANCE This ex vivo and in vitro study demonstrates that 2-DG inhibits angiogenesis with an action involving attenuation of VEGFR2 signaling and MMP-2 expression, possibly resulting from interference with N-linked glycosylation of VEGFR2. 26285173 5 22 theme metalloproteinase 859:875 arg1 migration 782:790 migration 782:790 migration 782:790 2-DG (0.1-1.0mM) also significantly inhibited cell invasion and migration, as well as the activity and mRNA and protein expression of matrix metalloproteinase (MMP)-2 in HUVECs. 26285173 5 22 theme metalloproteinase 859:875 arg1 expression 838:847 mRNA and protein expression 821:847 expression 838:847 2-DG (0.1-1.0mM) also significantly inhibited cell invasion and migration, as well as the activity and mRNA and protein expression of matrix metalloproteinase (MMP)-2 in HUVECs. 26285173 5 22 theme metalloproteinase 859:875 arg1 invasion 769:776 cell invasion 764:776 cell invasion 764:776 2-DG (0.1-1.0mM) also significantly inhibited cell invasion and migration, as well as the activity and mRNA and protein expression of matrix metalloproteinase (MMP)-2 in HUVECs. 26285173 5 22 theme metalloproteinase 859:875 arg1 activity 808:815 activity 808:815 activity 808:815 2-DG (0.1-1.0mM) also significantly inhibited cell invasion and migration, as well as the activity and mRNA and protein expression of matrix metalloproteinase (MMP)-2 in HUVECs. 26285173 6 23 theme protein 955:961 arg1 expression 963:972 mRNA and protein expression 946:972 mRNA and protein expression of vascular endothelial growth receptor 2 (VEGFR2) 946:1023 In addition, 2-DG (1.0mM) significantly inhibited mRNA and protein expression of vascular endothelial growth receptor 2 (VEGFR2) in a time-dependent manner. 26285173 4 24 theme rat 689:691 arg1 rings 700:704 rat aortic rings 689:704 rat aortic rings 689:704 KEY FINDINGS Results reveal that 2-DG (0.05-1.0mM) significantly inhibited tube formation in both rat aortic rings and HUVECs. 26285173 7 25 theme kinase 1172:1177 arg1 phosphorylation 1091:1105 the phosphorylation 1087:1105 the phosphorylation of the focal adhesion kinase (FAK) and mitogen-activated protein kinase (p38), the downstream molecules of VEGFR2 1087:1219 2-DG also significantly inhibited the phosphorylation of the focal adhesion kinase (FAK) and mitogen-activated protein kinase (p38), the downstream molecules of VEGFR2. 26285173 1 26 theme glucose 150:156 arg1 analogue 158:165 a glucose analogue 148:165 a glucose analogue 148:165 AIMS 2-Deoxyglucose (2-DG) is a glucose analogue and has been shown to inhibit angiogenesis in human umbilical vascular endothelial cells (HUVECs) through interference with N-linked glycosylation. 26285173 1 26 theme glucose 150:156 arg1 2-Deoxyglucose 123:136 AIMS 2-Deoxyglucose 118:136 AIMS 2-Deoxyglucose (2-DG) 118:143 AIMS 2-Deoxyglucose (2-DG) is a glucose analogue and has been shown to inhibit angiogenesis in human umbilical vascular endothelial cells (HUVECs) through interference with N-linked glycosylation. 26285173 6 27 theme mRNA 946:949 arg1 expression 963:972 mRNA and protein expression 946:972 mRNA and protein expression of vascular endothelial growth receptor 2 (VEGFR2) 946:1023 In addition, 2-DG (1.0mM) significantly inhibited mRNA and protein expression of vascular endothelial growth receptor 2 (VEGFR2) in a time-dependent manner. 26285173 7 28 theme mitogen-activated 1146:1162 arg1 kinase 1172:1177 mitogen-activated protein kinase 1146:1177 mitogen-activated protein kinase (p38) 1146:1183 2-DG also significantly inhibited the phosphorylation of the focal adhesion kinase (FAK) and mitogen-activated protein kinase (p38), the downstream molecules of VEGFR2. 26285173 7 28 theme mitogen-activated 1146:1162 arg1 p38 1180:1182 p38 1180:1182 p38 1180:1182 2-DG also significantly inhibited the phosphorylation of the focal adhesion kinase (FAK) and mitogen-activated protein kinase (p38), the downstream molecules of VEGFR2. 26285173 8 29 from effects 1226:1232 arg1 expression 1296:1305 VEGFR2 protein expression 1281:1305 VEGFR2 protein expression in HUVECs 1281:1315 The effects of 2-DG on tube formation, MMP-2 activity, and VEGFR2 protein expression in HUVECs were reversed by mannose, an N-linked glycosylation precursor. 26285173 8 29 from effects 1226:1232 arg1 formation 1250:1258 tube formation 1245:1258 tube formation 1245:1258 The effects of 2-DG on tube formation, MMP-2 activity, and VEGFR2 protein expression in HUVECs were reversed by mannose, an N-linked glycosylation precursor. 26285173 8 29 from effects 1226:1232 arg1 activity 1267:1274 MMP-2 activity 1261:1274 MMP-2 activity 1261:1274 The effects of 2-DG on tube formation, MMP-2 activity, and VEGFR2 protein expression in HUVECs were reversed by mannose, an N-linked glycosylation precursor. 26285173 0 30 from attenuation 54:64 arg1 HUVECs 110:115 HUVECs 110:115 HUVECs 110:115 The anti-angiogenic action of 2-deoxyglucose involves attenuation of VEGFR2 signaling and MMP-2 expression in HUVECs. 26285173 3 31 dep METHODS 394:400 arg1 used 513:516 used 513:516 used HUVECs to investigate the molecular mechanism underlying such an action 513:588 MAIN METHODS We first employed an ex vivo rat aortic ring model to substantiate the anti-angiogenic action of 2-DG and then used HUVECs to investigate the molecular mechanism underlying such an action. 26285173 3 31 dep METHODS 394:400 arg1 employed 411:418 employed 411:418 employed an ex vivo rat aortic ring model to substantiate the anti-angiogenic action of 2-DG 411:502 MAIN METHODS We first employed an ex vivo rat aortic ring model to substantiate the anti-angiogenic action of 2-DG and then used HUVECs to investigate the molecular mechanism underlying such an action. 26285173 10 32 theme signaling 1605:1613 arg1 attenuation 1583:1593 attenuation 1583:1593 attenuation of VEGFR2 signaling and MMP-2 expression 1583:1634 SIGNIFICANCE This ex vivo and in vitro study demonstrates that 2-DG inhibits angiogenesis with an action involving attenuation of VEGFR2 signaling and MMP-2 expression, possibly resulting from interference with N-linked glycosylation of VEGFR2. 26285173 8 33 theme protein 1288:1294 arg1 expression 1296:1305 VEGFR2 protein expression 1281:1305 VEGFR2 protein expression in HUVECs 1281:1315 The effects of 2-DG on tube formation, MMP-2 activity, and VEGFR2 protein expression in HUVECs were reversed by mannose, an N-linked glycosylation precursor. 26285173 7 34 theme adhesion 1120:1127 arg1 FAK 1137:1139 FAK 1137:1139 FAK 1137:1139 2-DG also significantly inhibited the phosphorylation of the focal adhesion kinase (FAK) and mitogen-activated protein kinase (p38), the downstream molecules of VEGFR2. 26285173 7 34 theme adhesion 1120:1127 arg1 kinase 1129:1134 focal adhesion kinase 1114:1134 focal adhesion kinase (FAK) 1114:1140 2-DG also significantly inhibited the phosphorylation of the focal adhesion kinase (FAK) and mitogen-activated protein kinase (p38), the downstream molecules of VEGFR2. 26285173 7 34 theme adhesion 1120:1127 arg1 molecules 1201:1209 the downstream molecules 1186:1209 the downstream molecules of VEGFR2 1186:1219 2-DG also significantly inhibited the phosphorylation of the focal adhesion kinase (FAK) and mitogen-activated protein kinase (p38), the downstream molecules of VEGFR2. 26285173 6 35 theme receptor 1005:1012 arg1 expression 963:972 mRNA and protein expression 946:972 mRNA and protein expression of vascular endothelial growth receptor 2 (VEGFR2) 946:1023 In addition, 2-DG (1.0mM) significantly inhibited mRNA and protein expression of vascular endothelial growth receptor 2 (VEGFR2) in a time-dependent manner. 26285173 3 36 theme aortic 435:440 arg1 model 447:451 an ex vivo rat aortic ring model 420:451 an ex vivo rat aortic ring model 420:451 MAIN METHODS We first employed an ex vivo rat aortic ring model to substantiate the anti-angiogenic action of 2-DG and then used HUVECs to investigate the molecular mechanism underlying such an action. 26285173 10 37 theme MMP-2 1619:1623 arg1 expression 1625:1634 MMP-2 expression 1619:1634 MMP-2 expression 1619:1634 SIGNIFICANCE This ex vivo and in vitro study demonstrates that 2-DG inhibits angiogenesis with an action involving attenuation of VEGFR2 signaling and MMP-2 expression, possibly resulting from interference with N-linked glycosylation of VEGFR2. 26285173 0 38 theme 2-deoxyglucose 30:43 arg1 action 20:25 The anti-angiogenic action 0:25 The anti-angiogenic action of 2-deoxyglucose 0:43 The anti-angiogenic action of 2-deoxyglucose involves attenuation of VEGFR2 signaling and MMP-2 expression in HUVECs. 26285173 1 39 theme N-linked 291:298 arg1 glycosylation 300:312 N-linked glycosylation 291:312 N-linked glycosylation 291:312 AIMS 2-Deoxyglucose (2-DG) is a glucose analogue and has been shown to inhibit angiogenesis in human umbilical vascular endothelial cells (HUVECs) through interference with N-linked glycosylation. 26285173 10 40 with interference 1661:1672 arg1 glycosylation 1688:1700 N-linked glycosylation 1679:1700 N-linked glycosylation of VEGFR2 1679:1710 SIGNIFICANCE This ex vivo and in vitro study demonstrates that 2-DG inhibits angiogenesis with an action involving attenuation of VEGFR2 signaling and MMP-2 expression, possibly resulting from interference with N-linked glycosylation of VEGFR2. 26285173 3 41 dep ex 423:424 arg1 vivo 426:429 vivo 426:429 vivo 426:429 MAIN METHODS We first employed an ex vivo rat aortic ring model to substantiate the anti-angiogenic action of 2-DG and then used HUVECs to investigate the molecular mechanism underlying such an action. 26285173 6 42 theme endothelial 986:996 arg1 receptor 1005:1012 vascular endothelial growth receptor 2 977:1014 vascular endothelial growth receptor 2 (VEGFR2) 977:1023 In addition, 2-DG (1.0mM) significantly inhibited mRNA and protein expression of vascular endothelial growth receptor 2 (VEGFR2) in a time-dependent manner. 26285173 6 42 theme endothelial 986:996 arg1 VEGFR2 1017:1022 VEGFR2 1017:1022 VEGFR2 1017:1022 In addition, 2-DG (1.0mM) significantly inhibited mRNA and protein expression of vascular endothelial growth receptor 2 (VEGFR2) in a time-dependent manner. 26285173 5 43 theme matrix 852:857 arg1 MMP 878:880 MMP 878:880 MMP 878:880 2-DG (0.1-1.0mM) also significantly inhibited cell invasion and migration, as well as the activity and mRNA and protein expression of matrix metalloproteinase (MMP)-2 in HUVECs. 26285173 5 43 theme matrix 852:857 arg1 metalloproteinase 859:875 matrix metalloproteinase 852:875 matrix metalloproteinase (MMP)-2 852:883 2-DG (0.1-1.0mM) also significantly inhibited cell invasion and migration, as well as the activity and mRNA and protein expression of matrix metalloproteinase (MMP)-2 in HUVECs. 26285173 3 44 theme anti-angiogenic 473:487 arg1 action 489:494 the anti-angiogenic action 469:494 the anti-angiogenic action of 2-DG 469:502 MAIN METHODS We first employed an ex vivo rat aortic ring model to substantiate the anti-angiogenic action of 2-DG and then used HUVECs to investigate the molecular mechanism underlying such an action. 26285173 11 45 theme actual 1806:1811 arg1 status 1813:1818 the actual status 1802:1818 the actual status of N-glycosylation of VEGFR2 1802:1847 Further studies are needed to show that 2-DG inhibits VEGF-mediated angiogenesis or that the actual status of N-glycosylation of VEGFR2 is affected by the treatment. 26285173 4 46 theme KEY 591:593 arg1 Results 604:610 KEY FINDINGS Results 591:610 KEY FINDINGS Results 591:610 KEY FINDINGS Results reveal that 2-DG (0.05-1.0mM) significantly inhibited tube formation in both rat aortic rings and HUVECs. 26285173 8 47 theme N-linked 1346:1353 arg1 precursor 1369:1377 an N-linked glycosylation precursor 1343:1377 an N-linked glycosylation precursor 1343:1377 The effects of 2-DG on tube formation, MMP-2 activity, and VEGFR2 protein expression in HUVECs were reversed by mannose, an N-linked glycosylation precursor. 26285173 8 47 theme N-linked 1346:1353 arg1 mannose 1334:1340 mannose 1334:1340 mannose 1334:1340 The effects of 2-DG on tube formation, MMP-2 activity, and VEGFR2 protein expression in HUVECs were reversed by mannose, an N-linked glycosylation precursor. 26285173 1 48 theme umbilical 219:227 arg1 cells 250:254 human umbilical vascular endothelial cells 213:254 human umbilical vascular endothelial cells (HUVECs) 213:263 AIMS 2-Deoxyglucose (2-DG) is a glucose analogue and has been shown to inhibit angiogenesis in human umbilical vascular endothelial cells (HUVECs) through interference with N-linked glycosylation. 26285173 1 48 theme umbilical 219:227 arg1 HUVECs 257:262 HUVECs 257:262 HUVECs 257:262 AIMS 2-Deoxyglucose (2-DG) is a glucose analogue and has been shown to inhibit angiogenesis in human umbilical vascular endothelial cells (HUVECs) through interference with N-linked glycosylation. 26285173 7 49 theme downstream 1190:1199 arg1 kinase 1129:1134 focal adhesion kinase 1114:1134 focal adhesion kinase (FAK) 1114:1140 2-DG also significantly inhibited the phosphorylation of the focal adhesion kinase (FAK) and mitogen-activated protein kinase (p38), the downstream molecules of VEGFR2. 26285173 7 49 theme downstream 1190:1199 arg1 molecules 1201:1209 the downstream molecules 1186:1209 the downstream molecules of VEGFR2 1186:1219 2-DG also significantly inhibited the phosphorylation of the focal adhesion kinase (FAK) and mitogen-activated protein kinase (p38), the downstream molecules of VEGFR2. 26285173 10 50 theme ex 1486:1487 arg1 study 1507:1511 This ex vivo and in vitro study 1481:1511 This ex vivo and in vitro study 1481:1511 SIGNIFICANCE This ex vivo and in vitro study demonstrates that 2-DG inhibits angiogenesis with an action involving attenuation of VEGFR2 signaling and MMP-2 expression, possibly resulting from interference with N-linked glycosylation of VEGFR2. 26285173 7 51 theme protein 1164:1170 arg1 kinase 1172:1177 mitogen-activated protein kinase 1146:1177 mitogen-activated protein kinase (p38) 1146:1183 2-DG also significantly inhibited the phosphorylation of the focal adhesion kinase (FAK) and mitogen-activated protein kinase (p38), the downstream molecules of VEGFR2. 26285173 7 51 theme protein 1164:1170 arg1 p38 1180:1182 p38 1180:1182 p38 1180:1182 2-DG also significantly inhibited the phosphorylation of the focal adhesion kinase (FAK) and mitogen-activated protein kinase (p38), the downstream molecules of VEGFR2. 26285173 2 52 theme 2-DG 358:361 arg1 mechanisms 344:353 the anti-angiogenic mechanisms 324:353 the anti-angiogenic mechanisms of 2-DG 324:361 However, the anti-angiogenic mechanisms of 2-DG are not fully elucidated. 26285173 8 53 from expression 1296:1305 arg1 HUVECs 1310:1315 HUVECs 1310:1315 HUVECs 1310:1315 The effects of 2-DG on tube formation, MMP-2 activity, and VEGFR2 protein expression in HUVECs were reversed by mannose, an N-linked glycosylation precursor. 26285173 1 54 theme endothelial 238:248 arg1 cells 250:254 human umbilical vascular endothelial cells 213:254 human umbilical vascular endothelial cells (HUVECs) 213:263 AIMS 2-Deoxyglucose (2-DG) is a glucose analogue and has been shown to inhibit angiogenesis in human umbilical vascular endothelial cells (HUVECs) through interference with N-linked glycosylation. 26285173 1 54 theme endothelial 238:248 arg1 HUVECs 257:262 HUVECs 257:262 HUVECs 257:262 AIMS 2-Deoxyglucose (2-DG) is a glucose analogue and has been shown to inhibit angiogenesis in human umbilical vascular endothelial cells (HUVECs) through interference with N-linked glycosylation. 26285173 1 55 with interference 273:284 arg1 glycosylation 300:312 N-linked glycosylation 291:312 N-linked glycosylation 291:312 AIMS 2-Deoxyglucose (2-DG) is a glucose analogue and has been shown to inhibit angiogenesis in human umbilical vascular endothelial cells (HUVECs) through interference with N-linked glycosylation. 26285173 3 56 used used 513:516 arg2 We 402:403 We 402:403 We 402:403 MAIN METHODS We first employed an ex vivo rat aortic ring model to substantiate the anti-angiogenic action of 2-DG and then used HUVECs to investigate the molecular mechanism underlying such an action. 26285173 11 57 theme VEGF-mediated 1767:1779 arg1 angiogenesis 1781:1792 VEGF-mediated angiogenesis 1767:1792 VEGF-mediated angiogenesis 1767:1792 Further studies are needed to show that 2-DG inhibits VEGF-mediated angiogenesis or that the actual status of N-glycosylation of VEGFR2 is affected by the treatment. 26285173 11 58 theme N-glycosylation 1823:1837 arg1 status 1813:1818 the actual status 1802:1818 the actual status of N-glycosylation of VEGFR2 1802:1847 Further studies are needed to show that 2-DG inhibits VEGF-mediated angiogenesis or that the actual status of N-glycosylation of VEGFR2 is affected by the treatment. 26285173 9 59 theme 2-DG-induced 1402:1413 arg1 accumulation 1415:1426 2-DG-induced accumulation 1402:1426 2-DG-induced accumulation of VEGFR2 in the endoplasmic reticulum 1402:1465 Mannose also reversed 2-DG-induced accumulation of VEGFR2 in the endoplasmic reticulum. 26285173 10 60 dep ex 1486:1487 arg1 vivo 1489:1492 vivo 1489:1492 vivo 1489:1492 SIGNIFICANCE This ex vivo and in vitro study demonstrates that 2-DG inhibits angiogenesis with an action involving attenuation of VEGFR2 signaling and MMP-2 expression, possibly resulting from interference with N-linked glycosylation of VEGFR2. 26285173 1 61 theme AIMS 118:121 arg1 analogue 158:165 a glucose analogue 148:165 a glucose analogue 148:165 AIMS 2-Deoxyglucose (2-DG) is a glucose analogue and has been shown to inhibit angiogenesis in human umbilical vascular endothelial cells (HUVECs) through interference with N-linked glycosylation. 26285173 1 61 theme AIMS 118:121 arg1 2-DG 139:142 2-DG 139:142 2-DG 139:142 AIMS 2-Deoxyglucose (2-DG) is a glucose analogue and has been shown to inhibit angiogenesis in human umbilical vascular endothelial cells (HUVECs) through interference with N-linked glycosylation. 26285173 1 61 theme AIMS 118:121 arg1 2-Deoxyglucose 123:136 AIMS 2-Deoxyglucose 118:136 AIMS 2-Deoxyglucose (2-DG) 118:143 AIMS 2-Deoxyglucose (2-DG) is a glucose analogue and has been shown to inhibit angiogenesis in human umbilical vascular endothelial cells (HUVECs) through interference with N-linked glycosylation. 26285173 11 62 gly N-glycosylation 1823:1837 arg1 VEGFR2 1842:1847 VEGFR2 1842:1847 VEGFR2 1842:1847 Further studies are needed to show that 2-DG inhibits VEGF-mediated angiogenesis or that the actual status of N-glycosylation of VEGFR2 is affected by the treatment. 26285173 4 63 theme aortic 693:698 arg1 rings 700:704 rat aortic rings 689:704 rat aortic rings 689:704 KEY FINDINGS Results reveal that 2-DG (0.05-1.0mM) significantly inhibited tube formation in both rat aortic rings and HUVECs. 26285173 5 64 from activity 808:815 arg1 HUVECs 888:893 HUVECs 888:893 HUVECs 888:893 2-DG (0.1-1.0mM) also significantly inhibited cell invasion and migration, as well as the activity and mRNA and protein expression of matrix metalloproteinase (MMP)-2 in HUVECs. 26285173 6 65 theme vascular 977:984 arg1 receptor 1005:1012 vascular endothelial growth receptor 2 977:1014 vascular endothelial growth receptor 2 (VEGFR2) 977:1023 In addition, 2-DG (1.0mM) significantly inhibited mRNA and protein expression of vascular endothelial growth receptor 2 (VEGFR2) in a time-dependent manner. 26285173 6 65 theme vascular 977:984 arg1 VEGFR2 1017:1022 VEGFR2 1017:1022 VEGFR2 1017:1022 In addition, 2-DG (1.0mM) significantly inhibited mRNA and protein expression of vascular endothelial growth receptor 2 (VEGFR2) in a time-dependent manner. 26285173 0 66 theme signaling 76:84 arg1 attenuation 54:64 attenuation 54:64 attenuation of VEGFR2 signaling 54:84 The anti-angiogenic action of 2-deoxyglucose involves attenuation of VEGFR2 signaling and MMP-2 expression in HUVECs. 26285173 0 66 theme signaling 76:84 arg1 expression 96:105 MMP-2 expression 90:105 MMP-2 expression in HUVECs 90:115 The anti-angiogenic action of 2-deoxyglucose involves attenuation of VEGFR2 signaling and MMP-2 expression in HUVECs. 26285173 9 67 theme endoplasmic 1445:1455 arg1 reticulum 1457:1465 the endoplasmic reticulum 1441:1465 the endoplasmic reticulum 1441:1465 Mannose also reversed 2-DG-induced accumulation of VEGFR2 in the endoplasmic reticulum. 26285173 0 68 theme MMP-2 90:94 arg1 expression 96:105 MMP-2 expression 90:105 MMP-2 expression in HUVECs 90:115 The anti-angiogenic action of 2-deoxyglucose involves attenuation of VEGFR2 signaling and MMP-2 expression in HUVECs. 26285173 5 69 from migration 782:790 arg1 HUVECs 888:893 HUVECs 888:893 HUVECs 888:893 2-DG (0.1-1.0mM) also significantly inhibited cell invasion and migration, as well as the activity and mRNA and protein expression of matrix metalloproteinase (MMP)-2 in HUVECs. 26285173 11 70 theme VEGFR2 1842:1847 arg1 N-glycosylation 1823:1837 N-glycosylation 1823:1837 N-glycosylation of VEGFR2 1823:1847 Further studies are needed to show that 2-DG inhibits VEGF-mediated angiogenesis or that the actual status of N-glycosylation of VEGFR2 is affected by the treatment. 26285173 8 71 link N-linked 1346:1353 arg1 precursor 1369:1377 an N-linked glycosylation precursor 1343:1377 an N-linked glycosylation precursor 1343:1377 The effects of 2-DG on tube formation, MMP-2 activity, and VEGFR2 protein expression in HUVECs were reversed by mannose, an N-linked glycosylation precursor. 26285173 8 71 link N-linked 1346:1353 arg1 mannose 1334:1340 mannose 1334:1340 mannose 1334:1340 The effects of 2-DG on tube formation, MMP-2 activity, and VEGFR2 protein expression in HUVECs were reversed by mannose, an N-linked glycosylation precursor. 26285173 5 72 from invasion 769:776 arg1 HUVECs 888:893 HUVECs 888:893 HUVECs 888:893 2-DG (0.1-1.0mM) also significantly inhibited cell invasion and migration, as well as the activity and mRNA and protein expression of matrix metalloproteinase (MMP)-2 in HUVECs. 26285173 8 73 theme MMP-2 1261:1265 arg1 activity 1267:1274 MMP-2 activity 1261:1274 MMP-2 activity 1261:1274 The effects of 2-DG on tube formation, MMP-2 activity, and VEGFR2 protein expression in HUVECs were reversed by mannose, an N-linked glycosylation precursor. 26285173 10 74 theme VEGFR2 1598:1603 arg1 signaling 1605:1613 VEGFR2 signaling 1598:1613 VEGFR2 signaling 1598:1613 SIGNIFICANCE This ex vivo and in vitro study demonstrates that 2-DG inhibits angiogenesis with an action involving attenuation of VEGFR2 signaling and MMP-2 expression, possibly resulting from interference with N-linked glycosylation of VEGFR2. 26285173 0 75 theme anti-angiogenic 4:18 arg1 action 20:25 The anti-angiogenic action 0:25 The anti-angiogenic action of 2-deoxyglucose 0:43 The anti-angiogenic action of 2-deoxyglucose involves attenuation of VEGFR2 signaling and MMP-2 expression in HUVECs. 26285173 8 76 from formation 1250:1258 arg1 HUVECs 1310:1315 HUVECs 1310:1315 HUVECs 1310:1315 The effects of 2-DG on tube formation, MMP-2 activity, and VEGFR2 protein expression in HUVECs were reversed by mannose, an N-linked glycosylation precursor. 26285173 3 77 theme MAIN 389:392 arg1 METHODS 394:400 MAIN METHODS 389:400 MAIN METHODS We first employed an ex vivo rat aortic ring model to substantiate the anti-angiogenic action of 2-DG and then used HUVECs to investigate the molecular mechanism underlying such an action. 389:589 MAIN METHODS We first employed an ex vivo rat aortic ring model to substantiate the anti-angiogenic action of 2-DG and then used HUVECs to investigate the molecular mechanism underlying such an action. 26285173 8 78 theme VEGFR2 1281:1286 arg1 expression 1296:1305 VEGFR2 protein expression 1281:1305 VEGFR2 protein expression in HUVECs 1281:1315 The effects of 2-DG on tube formation, MMP-2 activity, and VEGFR2 protein expression in HUVECs were reversed by mannose, an N-linked glycosylation precursor. 26285173 3 79 theme ex 423:424 arg1 model 447:451 an ex vivo rat aortic ring model 420:451 an ex vivo rat aortic ring model 420:451 MAIN METHODS We first employed an ex vivo rat aortic ring model to substantiate the anti-angiogenic action of 2-DG and then used HUVECs to investigate the molecular mechanism underlying such an action. 26285173 7 80 theme focal 1114:1118 arg1 FAK 1137:1139 FAK 1137:1139 FAK 1137:1139 2-DG also significantly inhibited the phosphorylation of the focal adhesion kinase (FAK) and mitogen-activated protein kinase (p38), the downstream molecules of VEGFR2. 26285173 7 80 theme focal 1114:1118 arg1 kinase 1129:1134 focal adhesion kinase 1114:1134 focal adhesion kinase (FAK) 1114:1140 2-DG also significantly inhibited the phosphorylation of the focal adhesion kinase (FAK) and mitogen-activated protein kinase (p38), the downstream molecules of VEGFR2. 26285173 7 80 theme focal 1114:1118 arg1 molecules 1201:1209 the downstream molecules 1186:1209 the downstream molecules of VEGFR2 1186:1219 2-DG also significantly inhibited the phosphorylation of the focal adhesion kinase (FAK) and mitogen-activated protein kinase (p38), the downstream molecules of VEGFR2. 26285173 10 81 theme expression 1625:1634 arg1 attenuation 1583:1593 attenuation 1583:1593 attenuation of VEGFR2 signaling and MMP-2 expression 1583:1634 SIGNIFICANCE This ex vivo and in vitro study demonstrates that 2-DG inhibits angiogenesis with an action involving attenuation of VEGFR2 signaling and MMP-2 expression, possibly resulting from interference with N-linked glycosylation of VEGFR2. 26285173 5 82 theme cell 764:767 arg1 invasion 769:776 cell invasion 764:776 cell invasion 764:776 2-DG (0.1-1.0mM) also significantly inhibited cell invasion and migration, as well as the activity and mRNA and protein expression of matrix metalloproteinase (MMP)-2 in HUVECs. 26285173 6 83 theme growth 998:1003 arg1 receptor 1005:1012 vascular endothelial growth receptor 2 977:1014 vascular endothelial growth receptor 2 (VEGFR2) 977:1023 In addition, 2-DG (1.0mM) significantly inhibited mRNA and protein expression of vascular endothelial growth receptor 2 (VEGFR2) in a time-dependent manner. 26285173 6 83 theme growth 998:1003 arg1 VEGFR2 1017:1022 VEGFR2 1017:1022 VEGFR2 1017:1022 In addition, 2-DG (1.0mM) significantly inhibited mRNA and protein expression of vascular endothelial growth receptor 2 (VEGFR2) in a time-dependent manner. 26285173 3 84 theme ring 442:445 arg1 model 447:451 an ex vivo rat aortic ring model 420:451 an ex vivo rat aortic ring model 420:451 MAIN METHODS We first employed an ex vivo rat aortic ring model to substantiate the anti-angiogenic action of 2-DG and then used HUVECs to investigate the molecular mechanism underlying such an action. 26285173 9 85 from accumulation 1415:1426 arg1 reticulum 1457:1465 the endoplasmic reticulum 1441:1465 the endoplasmic reticulum 1441:1465 Mannose also reversed 2-DG-induced accumulation of VEGFR2 in the endoplasmic reticulum. 26285173 7 86 theme VEGFR2 1214:1219 arg1 kinase 1129:1134 focal adhesion kinase 1114:1134 focal adhesion kinase (FAK) 1114:1140 2-DG also significantly inhibited the phosphorylation of the focal adhesion kinase (FAK) and mitogen-activated protein kinase (p38), the downstream molecules of VEGFR2. 26285173 7 86 theme VEGFR2 1214:1219 arg1 molecules 1201:1209 the downstream molecules 1186:1209 the downstream molecules of VEGFR2 1186:1219 2-DG also significantly inhibited the phosphorylation of the focal adhesion kinase (FAK) and mitogen-activated protein kinase (p38), the downstream molecules of VEGFR2. 26285173 1 87 link N-linked 291:298 arg1 glycosylation 300:312 N-linked glycosylation 291:312 N-linked glycosylation 291:312 AIMS 2-Deoxyglucose (2-DG) is a glucose analogue and has been shown to inhibit angiogenesis in human umbilical vascular endothelial cells (HUVECs) through interference with N-linked glycosylation. 26285173 2 88 theme anti-angiogenic 328:342 arg1 mechanisms 344:353 the anti-angiogenic mechanisms 324:353 the anti-angiogenic mechanisms of 2-DG 324:361 However, the anti-angiogenic mechanisms of 2-DG are not fully elucidated. 26285173 4 89 theme FINDINGS 595:602 arg1 Results 604:610 KEY FINDINGS Results 591:610 KEY FINDINGS Results 591:610 KEY FINDINGS Results reveal that 2-DG (0.05-1.0mM) significantly inhibited tube formation in both rat aortic rings and HUVECs. 26285173 8 90 from activity 1267:1274 arg1 HUVECs 1310:1315 HUVECs 1310:1315 HUVECs 1310:1315 The effects of 2-DG on tube formation, MMP-2 activity, and VEGFR2 protein expression in HUVECs were reversed by mannose, an N-linked glycosylation precursor. 26285173 1 91 theme human 213:217 arg1 cells 250:254 human umbilical vascular endothelial cells 213:254 human umbilical vascular endothelial cells (HUVECs) 213:263 AIMS 2-Deoxyglucose (2-DG) is a glucose analogue and has been shown to inhibit angiogenesis in human umbilical vascular endothelial cells (HUVECs) through interference with N-linked glycosylation. 26285173 1 91 theme human 213:217 arg1 HUVECs 257:262 HUVECs 257:262 HUVECs 257:262 AIMS 2-Deoxyglucose (2-DG) is a glucose analogue and has been shown to inhibit angiogenesis in human umbilical vascular endothelial cells (HUVECs) through interference with N-linked glycosylation. 26285173 3 92 theme rat 431:433 arg1 model 447:451 an ex vivo rat aortic ring model 420:451 an ex vivo rat aortic ring model 420:451 MAIN METHODS We first employed an ex vivo rat aortic ring model to substantiate the anti-angiogenic action of 2-DG and then used HUVECs to investigate the molecular mechanism underlying such an action. 26285173 5 93 dep activity 808:815 arg1 the 804:806 the 804:806 the 804:806 2-DG (0.1-1.0mM) also significantly inhibited cell invasion and migration, as well as the activity and mRNA and protein expression of matrix metalloproteinase (MMP)-2 in HUVECs. 26285173 7 94 theme kinase 1129:1134 arg1 phosphorylation 1091:1105 the phosphorylation 1087:1105 the phosphorylation of the focal adhesion kinase (FAK) and mitogen-activated protein kinase (p38), the downstream molecules of VEGFR2 1087:1219 2-DG also significantly inhibited the phosphorylation of the focal adhesion kinase (FAK) and mitogen-activated protein kinase (p38), the downstream molecules of VEGFR2. 26285173 1 95 theme vascular 229:236 arg1 cells 250:254 human umbilical vascular endothelial cells 213:254 human umbilical vascular endothelial cells (HUVECs) 213:263 AIMS 2-Deoxyglucose (2-DG) is a glucose analogue and has been shown to inhibit angiogenesis in human umbilical vascular endothelial cells (HUVECs) through interference with N-linked glycosylation. 26285173 1 95 theme vascular 229:236 arg1 HUVECs 257:262 HUVECs 257:262 HUVECs 257:262 AIMS 2-Deoxyglucose (2-DG) is a glucose analogue and has been shown to inhibit angiogenesis in human umbilical vascular endothelial cells (HUVECs) through interference with N-linked glycosylation. 28297656 8 0 theme acyl 1557:1560 arg1 chain 1562:1566 the acyl chain 1553:1566 the acyl chain 1553:1566 2H NMR data for 10 mol % stearoyl ceramide in POPC also showed that the long-chain base was more ordered than the acyl chain at comparable chain positions and temperatures. 28297656 6 1 theme bilayer 1225:1231 arg1 concentrations 1233:1246 lower bilayer concentrations 1219:1246 lower bilayer concentrations 1219:1246 Finally, we compared two ceramide analogs with equal carbon numbers (d16:1/17:0 or d20:1/13:0) and observed that the analog with a longer sphingoid base segregated at lower bilayer concentrations to a ceramide-rich phase compared with the shorter sphingoid base analog. 28297656 7 2 theme d16:1/17:0 1422:1431 arg1 ceramide 1433:1440 d16:1/17:0 ceramide 1422:1440 d16:1/17:0 ceramide 1422:1440 The gel phase formed by d20:1/13:0 ceramide also was more thermostable than the gel phase formed by d16:1/17:0 ceramide. 28297656 3 3 from d20:1 505:509 arg1 ceramide 526:533 N-palmitoyl ceramide 514:533 N-palmitoyl ceramide 514:533 The longer the length of the long-chain base (d16:1, d17:1, d18:1, d19:1, and d20:1 in N-palmitoyl ceramide), the less ceramide was needed for the onset of lateral segregation and ceramide-rich phase formation. 28297656 4 4 theme similar 640:646 arg1 trend 664:668 A similar but much weaker trend 638:668 A similar but much weaker trend 638:668 A similar but much weaker trend was observed when sphingosine (d18:1)-based ceramide had N-linked acyl chains of increasing length (14:0 and 16:0-20:0 in one-carbon increments). 28297656 2 5 theme Lateral 290:296 arg1 segregation 298:308 Lateral segregation 290:308 Lateral segregation 290:308 Lateral segregation and ceramide-rich phase formation was ascertained by a lifetime analysis of trans-parinaric acid (tPA) fluorescence. 28297656 1 6 theme acyl 162:165 arg1 chain 167:171 the N-linked acyl chain 149:171 the N-linked acyl chain of ceramides 149:184 We examined how the length of the long-chain base or the N-linked acyl chain of ceramides affected their lateral segregation in 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayers. 28297656 7 7 theme gel 1402:1404 arg1 phase 1406:1410 the gel phase 1398:1410 the gel phase formed by d16:1/17:0 ceramide 1398:1440 The gel phase formed by d20:1/13:0 ceramide also was more thermostable than the gel phase formed by d16:1/17:0 ceramide. 28297656 6 8 dep numbers 1112:1118 arg1 d16:1/17:0 1121:1130 d16:1/17:0 1121:1130 d16:1/17:0 1121:1130 Finally, we compared two ceramide analogs with equal carbon numbers (d16:1/17:0 or d20:1/13:0) and observed that the analog with a longer sphingoid base segregated at lower bilayer concentrations to a ceramide-rich phase compared with the shorter sphingoid base analog. 28297656 6 8 dep numbers 1112:1118 arg1 numbers 1112:1118 equal carbon numbers 1099:1118 equal carbon numbers (d16:1/17:0 or d20:1/13:0) 1099:1145 Finally, we compared two ceramide analogs with equal carbon numbers (d16:1/17:0 or d20:1/13:0) and observed that the analog with a longer sphingoid base segregated at lower bilayer concentrations to a ceramide-rich phase compared with the shorter sphingoid base analog. 28297656 6 8 dep numbers 1112:1118 arg1 d20:1/13:0 1135:1144 d20:1/13:0 1135:1144 d20:1/13:0 1135:1144 Finally, we compared two ceramide analogs with equal carbon numbers (d16:1/17:0 or d20:1/13:0) and observed that the analog with a longer sphingoid base segregated at lower bilayer concentrations to a ceramide-rich phase compared with the shorter sphingoid base analog. 28297656 6 9 theme equal 1099:1103 arg1 d16:1/17:0 1121:1130 d16:1/17:0 1121:1130 d16:1/17:0 1121:1130 Finally, we compared two ceramide analogs with equal carbon numbers (d16:1/17:0 or d20:1/13:0) and observed that the analog with a longer sphingoid base segregated at lower bilayer concentrations to a ceramide-rich phase compared with the shorter sphingoid base analog. 28297656 6 9 theme equal 1099:1103 arg1 numbers 1112:1118 equal carbon numbers 1099:1118 equal carbon numbers (d16:1/17:0 or d20:1/13:0) 1099:1145 Finally, we compared two ceramide analogs with equal carbon numbers (d16:1/17:0 or d20:1/13:0) and observed that the analog with a longer sphingoid base segregated at lower bilayer concentrations to a ceramide-rich phase compared with the shorter sphingoid base analog. 28297656 6 9 theme equal 1099:1103 arg1 d20:1/13:0 1135:1144 d20:1/13:0 1135:1144 d20:1/13:0 1135:1144 Finally, we compared two ceramide analogs with equal carbon numbers (d16:1/17:0 or d20:1/13:0) and observed that the analog with a longer sphingoid base segregated at lower bilayer concentrations to a ceramide-rich phase compared with the shorter sphingoid base analog. 28297656 3 10 theme less 541:544 arg1 base 467:470 the long-chain base 452:470 the long-chain base (d16:1, d17:1, d18:1, d19:1, and d20:1 in N-palmitoyl ceramide) 452:534 The longer the length of the long-chain base (d16:1, d17:1, d18:1, d19:1, and d20:1 in N-palmitoyl ceramide), the less ceramide was needed for the onset of lateral segregation and ceramide-rich phase formation. 28297656 3 10 theme less 541:544 arg1 ceramide 546:553 the less ceramide 537:553 the less ceramide 537:553 The longer the length of the long-chain base (d16:1, d17:1, d18:1, d19:1, and d20:1 in N-palmitoyl ceramide), the less ceramide was needed for the onset of lateral segregation and ceramide-rich phase formation. 28297656 9 11 theme long-chain 1637:1646 arg1 important 1680:1688 important 1680:1688 important 1680:1688 We conclude that the long-chain base length of ceramide is more important than the acyl chain length in determining the lateral segregation of the ceramide-rich gel phase and intermolecular interactions therein. 28297656 9 11 theme long-chain 1637:1646 arg1 length 1653:1658 the long-chain base length 1633:1658 the long-chain base length of ceramide 1633:1670 We conclude that the long-chain base length of ceramide is more important than the acyl chain length in determining the lateral segregation of the ceramide-rich gel phase and intermolecular interactions therein. 28297656 5 12 theme chain 1038:1042 arg1 length 1044:1049 the N-acyl chain length 1027:1049 the N-acyl chain length 1027:1049 The apparent lateral packing of the ceramide-rich phase, as determined from the longest-lifetime component of tPA fluorescence, also correlated strongly with the long-chain base length, but not as strongly with the N-acyl chain length. 28297656 1 13 theme lateral 201:207 arg1 segregation 209:219 their lateral segregation 195:219 their lateral segregation in 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayers 195:287 We examined how the length of the long-chain base or the N-linked acyl chain of ceramides affected their lateral segregation in 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayers. 28297656 6 14 theme ceramide-rich 1253:1265 arg1 phase 1267:1271 a ceramide-rich phase 1251:1271 a ceramide-rich phase compared with the shorter sphingoid base analog 1251:1319 Finally, we compared two ceramide analogs with equal carbon numbers (d16:1/17:0 or d20:1/13:0) and observed that the analog with a longer sphingoid base segregated at lower bilayer concentrations to a ceramide-rich phase compared with the shorter sphingoid base analog. 28297656 4 15 from 16:0-20:0 779:787 arg1 increments 803:812 one-carbon increments 792:812 one-carbon increments 792:812 A similar but much weaker trend was observed when sphingosine (d18:1)-based ceramide had N-linked acyl chains of increasing length (14:0 and 16:0-20:0 in one-carbon increments). 28297656 9 16 theme ceramide 1663:1670 arg1 important 1680:1688 important 1680:1688 important 1680:1688 We conclude that the long-chain base length of ceramide is more important than the acyl chain length in determining the lateral segregation of the ceramide-rich gel phase and intermolecular interactions therein. 28297656 9 16 theme ceramide 1663:1670 arg1 length 1653:1658 the long-chain base length 1633:1658 the long-chain base length of ceramide 1633:1670 We conclude that the long-chain base length of ceramide is more important than the acyl chain length in determining the lateral segregation of the ceramide-rich gel phase and intermolecular interactions therein. 28297656 4 17 from 14:0 770:773 arg1 increments 803:812 one-carbon increments 792:812 one-carbon increments 792:812 A similar but much weaker trend was observed when sphingosine (d18:1)-based ceramide had N-linked acyl chains of increasing length (14:0 and 16:0-20:0 in one-carbon increments). 28297656 3 18 theme lateral 583:589 arg1 segregation 591:601 lateral segregation 583:601 lateral segregation 583:601 The longer the length of the long-chain base (d16:1, d17:1, d18:1, d19:1, and d20:1 in N-palmitoyl ceramide), the less ceramide was needed for the onset of lateral segregation and ceramide-rich phase formation. 28297656 1 19 theme base 141:144 arg1 length 116:121 the length 112:121 the length of the long-chain base or the N-linked acyl chain of ceramides 112:184 We examined how the length of the long-chain base or the N-linked acyl chain of ceramides affected their lateral segregation in 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayers. 28297656 8 20 theme 2H 1443:1444 arg1 data 1450:1453 2H NMR data 1443:1453 2H NMR data for 10 mol % stearoyl ceramide in POPC 1443:1492 2H NMR data for 10 mol % stearoyl ceramide in POPC also showed that the long-chain base was more ordered than the acyl chain at comparable chain positions and temperatures. 28297656 0 21 theme Lateral 75:81 arg1 Segregation 83:93 Lateral Segregation 75:93 Lateral Segregation 75:93 The Long-Chain Sphingoid Base of Ceramides Determines Their Propensity for Lateral Segregation. 28297656 9 22 theme acyl 1699:1702 arg1 length 1710:1715 the acyl chain length 1695:1715 the acyl chain length in determining the lateral segregation of the ceramide-rich gel phase and intermolecular interactions therein 1695:1825 We conclude that the long-chain base length of ceramide is more important than the acyl chain length in determining the lateral segregation of the ceramide-rich gel phase and intermolecular interactions therein. 28297656 4 23 theme acyl 736:739 arg1 chains 741:746 N-linked acyl chains 727:746 N-linked acyl chains of increasing length (14:0 and 16:0-20:0 in one-carbon increments) 727:813 A similar but much weaker trend was observed when sphingosine (d18:1)-based ceramide had N-linked acyl chains of increasing length (14:0 and 16:0-20:0 in one-carbon increments). 28297656 9 24 dep phase 1781:1785 arg1 therein 1819:1825 therein 1819:1825 therein 1819:1825 We conclude that the long-chain base length of ceramide is more important than the acyl chain length in determining the lateral segregation of the ceramide-rich gel phase and intermolecular interactions therein. 28297656 8 25 theme 10 mol 1459:1464 arg1 ceramide 1477:1484 10 mol % stearoyl ceramide 1459:1484 10 mol % stearoyl ceramide in POPC 1459:1492 2H NMR data for 10 mol % stearoyl ceramide in POPC also showed that the long-chain base was more ordered than the acyl chain at comparable chain positions and temperatures. 28297656 3 26 theme long-chain 456:465 arg1 base 467:470 the long-chain base 452:470 the long-chain base (d16:1, d17:1, d18:1, d19:1, and d20:1 in N-palmitoyl ceramide) 452:534 The longer the length of the long-chain base (d16:1, d17:1, d18:1, d19:1, and d20:1 in N-palmitoyl ceramide), the less ceramide was needed for the onset of lateral segregation and ceramide-rich phase formation. 28297656 3 26 theme long-chain 456:465 arg1 ceramide 546:553 the less ceramide 537:553 the less ceramide 537:553 The longer the length of the long-chain base (d16:1, d17:1, d18:1, d19:1, and d20:1 in N-palmitoyl ceramide), the less ceramide was needed for the onset of lateral segregation and ceramide-rich phase formation. 28297656 6 27 theme sphingoid 1299:1307 arg1 analog 1314:1319 the shorter sphingoid base analog 1287:1319 the shorter sphingoid base analog 1287:1319 Finally, we compared two ceramide analogs with equal carbon numbers (d16:1/17:0 or d20:1/13:0) and observed that the analog with a longer sphingoid base segregated at lower bilayer concentrations to a ceramide-rich phase compared with the shorter sphingoid base analog. 28297656 0 28 theme Ceramides 33:41 arg1 Base 25:28 The Long-Chain Sphingoid Base 0:28 The Long-Chain Sphingoid Base of Ceramides 0:41 The Long-Chain Sphingoid Base of Ceramides Determines Their Propensity for Lateral Segregation. 28297656 8 29 theme stearoyl 1468:1475 arg1 ceramide 1477:1484 10 mol % stearoyl ceramide 1459:1484 10 mol % stearoyl ceramide in POPC 1459:1492 2H NMR data for 10 mol % stearoyl ceramide in POPC also showed that the long-chain base was more ordered than the acyl chain at comparable chain positions and temperatures. 28297656 1 30 link N-linked 153:160 arg1 chain 167:171 the N-linked acyl chain 149:171 the N-linked acyl chain of ceramides 149:184 We examined how the length of the long-chain base or the N-linked acyl chain of ceramides affected their lateral segregation in 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayers. 28297656 4 31 theme -based 707:712 arg1 ceramide 714:721 sphingosine (d18:1)-based ceramide 688:721 sphingosine (d18:1)-based ceramide 688:721 A similar but much weaker trend was observed when sphingosine (d18:1)-based ceramide had N-linked acyl chains of increasing length (14:0 and 16:0-20:0 in one-carbon increments). 28297656 9 32 theme lateral 1736:1742 arg1 segregation 1744:1754 the lateral segregation 1732:1754 the lateral segregation of the ceramide-rich gel phase and intermolecular interactions therein 1732:1825 We conclude that the long-chain base length of ceramide is more important than the acyl chain length in determining the lateral segregation of the ceramide-rich gel phase and intermolecular interactions therein. 28297656 0 33 theme Sphingoid 15:23 arg1 Base 25:28 The Long-Chain Sphingoid Base 0:28 The Long-Chain Sphingoid Base of Ceramides 0:41 The Long-Chain Sphingoid Base of Ceramides Determines Their Propensity for Lateral Segregation. 28297656 5 34 theme tPA 926:928 arg1 fluorescence 930:941 tPA fluorescence 926:941 tPA fluorescence 926:941 The apparent lateral packing of the ceramide-rich phase, as determined from the longest-lifetime component of tPA fluorescence, also correlated strongly with the long-chain base length, but not as strongly with the N-acyl chain length. 28297656 5 35 theme apparent 820:827 arg1 packing 837:843 The apparent lateral packing 816:843 The apparent lateral packing of the ceramide-rich phase 816:870 The apparent lateral packing of the ceramide-rich phase, as determined from the longest-lifetime component of tPA fluorescence, also correlated strongly with the long-chain base length, but not as strongly with the N-acyl chain length. 28297656 9 36 theme ceramide-rich 1763:1775 arg1 phase 1781:1785 the ceramide-rich gel phase 1759:1785 the ceramide-rich gel phase 1759:1785 We conclude that the long-chain base length of ceramide is more important than the acyl chain length in determining the lateral segregation of the ceramide-rich gel phase and intermolecular interactions therein. 28297656 3 37 theme phase 621:625 arg1 formation 627:635 ceramide-rich phase formation 607:635 ceramide-rich phase formation 607:635 The longer the length of the long-chain base (d16:1, d17:1, d18:1, d19:1, and d20:1 in N-palmitoyl ceramide), the less ceramide was needed for the onset of lateral segregation and ceramide-rich phase formation. 28297656 4 38 theme one-carbon 792:801 arg1 increments 803:812 one-carbon increments 792:812 one-carbon increments 792:812 A similar but much weaker trend was observed when sphingosine (d18:1)-based ceramide had N-linked acyl chains of increasing length (14:0 and 16:0-20:0 in one-carbon increments). 28297656 3 39 from d16:1 473:477 arg1 ceramide 526:533 N-palmitoyl ceramide 514:533 N-palmitoyl ceramide 514:533 The longer the length of the long-chain base (d16:1, d17:1, d18:1, d19:1, and d20:1 in N-palmitoyl ceramide), the less ceramide was needed for the onset of lateral segregation and ceramide-rich phase formation. 28297656 3 40 dep base 467:470 arg1 d16:1 473:477 d16:1 473:477 d16:1 473:477 The longer the length of the long-chain base (d16:1, d17:1, d18:1, d19:1, and d20:1 in N-palmitoyl ceramide), the less ceramide was needed for the onset of lateral segregation and ceramide-rich phase formation. 28297656 3 40 dep base 467:470 arg1 d19:1 494:498 d19:1 494:498 d19:1 494:498 The longer the length of the long-chain base (d16:1, d17:1, d18:1, d19:1, and d20:1 in N-palmitoyl ceramide), the less ceramide was needed for the onset of lateral segregation and ceramide-rich phase formation. 28297656 3 40 dep base 467:470 arg1 d20:1 505:509 d20:1 505:509 d20:1 505:509 The longer the length of the long-chain base (d16:1, d17:1, d18:1, d19:1, and d20:1 in N-palmitoyl ceramide), the less ceramide was needed for the onset of lateral segregation and ceramide-rich phase formation. 28297656 3 40 dep base 467:470 arg1 d18:1 487:491 d18:1 487:491 d18:1 487:491 The longer the length of the long-chain base (d16:1, d17:1, d18:1, d19:1, and d20:1 in N-palmitoyl ceramide), the less ceramide was needed for the onset of lateral segregation and ceramide-rich phase formation. 28297656 3 40 dep base 467:470 arg1 d17:1 480:484 d17:1 480:484 d17:1 480:484 The longer the length of the long-chain base (d16:1, d17:1, d18:1, d19:1, and d20:1 in N-palmitoyl ceramide), the less ceramide was needed for the onset of lateral segregation and ceramide-rich phase formation. 28297656 6 41 theme ceramide 1077:1084 arg1 analogs 1086:1092 two ceramide analogs 1073:1092 two ceramide analogs 1073:1092 Finally, we compared two ceramide analogs with equal carbon numbers (d16:1/17:0 or d20:1/13:0) and observed that the analog with a longer sphingoid base segregated at lower bilayer concentrations to a ceramide-rich phase compared with the shorter sphingoid base analog. 28297656 9 42 theme phase 1781:1785 arg1 segregation 1744:1754 the lateral segregation 1732:1754 the lateral segregation of the ceramide-rich gel phase and intermolecular interactions therein 1732:1825 We conclude that the long-chain base length of ceramide is more important than the acyl chain length in determining the lateral segregation of the ceramide-rich gel phase and intermolecular interactions therein. 28297656 8 43 theme long-chain 1515:1524 arg1 base 1526:1529 the long-chain base 1511:1529 the long-chain base 1511:1529 2H NMR data for 10 mol % stearoyl ceramide in POPC also showed that the long-chain base was more ordered than the acyl chain at comparable chain positions and temperatures. 28297656 3 44 from d17:1 480:484 arg1 ceramide 526:533 N-palmitoyl ceramide 514:533 N-palmitoyl ceramide 514:533 The longer the length of the long-chain base (d16:1, d17:1, d18:1, d19:1, and d20:1 in N-palmitoyl ceramide), the less ceramide was needed for the onset of lateral segregation and ceramide-rich phase formation. 28297656 8 45 theme comparable 1571:1580 arg1 positions 1588:1596 comparable chain positions 1571:1596 comparable chain positions 1571:1596 2H NMR data for 10 mol % stearoyl ceramide in POPC also showed that the long-chain base was more ordered than the acyl chain at comparable chain positions and temperatures. 28297656 4 46 link N-linked 727:734 arg1 chains 741:746 N-linked acyl chains 727:746 N-linked acyl chains of increasing length (14:0 and 16:0-20:0 in one-carbon increments) 727:813 A similar but much weaker trend was observed when sphingosine (d18:1)-based ceramide had N-linked acyl chains of increasing length (14:0 and 16:0-20:0 in one-carbon increments). 28297656 9 47 theme intermolecular 1791:1804 arg1 interactions 1806:1817 intermolecular interactions 1791:1817 intermolecular interactions 1791:1817 We conclude that the long-chain base length of ceramide is more important than the acyl chain length in determining the lateral segregation of the ceramide-rich gel phase and intermolecular interactions therein. 28297656 5 48 theme lateral 829:835 arg1 packing 837:843 The apparent lateral packing 816:843 The apparent lateral packing of the ceramide-rich phase 816:870 The apparent lateral packing of the ceramide-rich phase, as determined from the longest-lifetime component of tPA fluorescence, also correlated strongly with the long-chain base length, but not as strongly with the N-acyl chain length. 28297656 1 49 theme 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine 224:271 arg1 bilayers 280:287 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayers 224:287 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayers 224:287 We examined how the length of the long-chain base or the N-linked acyl chain of ceramides affected their lateral segregation in 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayers. 28297656 5 50 theme long-chain 978:987 arg1 length 994:999 the long-chain base length 974:999 the long-chain base length 974:999 The apparent lateral packing of the ceramide-rich phase, as determined from the longest-lifetime component of tPA fluorescence, also correlated strongly with the long-chain base length, but not as strongly with the N-acyl chain length. 28297656 2 51 theme trans-parinaric 386:400 arg1 tPA 408:410 tPA 408:410 tPA 408:410 Lateral segregation and ceramide-rich phase formation was ascertained by a lifetime analysis of trans-parinaric acid (tPA) fluorescence. 28297656 2 51 theme trans-parinaric 386:400 arg1 acid 402:405 trans-parinaric acid 386:405 trans-parinaric acid (tPA) fluorescence 386:424 Lateral segregation and ceramide-rich phase formation was ascertained by a lifetime analysis of trans-parinaric acid (tPA) fluorescence. 28297656 6 52 theme lower 1219:1223 arg1 concentrations 1233:1246 lower bilayer concentrations 1219:1246 lower bilayer concentrations 1219:1246 Finally, we compared two ceramide analogs with equal carbon numbers (d16:1/17:0 or d20:1/13:0) and observed that the analog with a longer sphingoid base segregated at lower bilayer concentrations to a ceramide-rich phase compared with the shorter sphingoid base analog. 28297656 2 53 theme ceramide-rich 314:326 arg1 formation 334:342 ceramide-rich phase formation 314:342 ceramide-rich phase formation 314:342 Lateral segregation and ceramide-rich phase formation was ascertained by a lifetime analysis of trans-parinaric acid (tPA) fluorescence. 28297656 3 54 theme N-palmitoyl 514:524 arg1 ceramide 526:533 N-palmitoyl ceramide 514:533 N-palmitoyl ceramide 514:533 The longer the length of the long-chain base (d16:1, d17:1, d18:1, d19:1, and d20:1 in N-palmitoyl ceramide), the less ceramide was needed for the onset of lateral segregation and ceramide-rich phase formation. 28297656 1 55 theme chain 167:171 arg1 length 116:121 the length 112:121 the length of the long-chain base or the N-linked acyl chain of ceramides 112:184 We examined how the length of the long-chain base or the N-linked acyl chain of ceramides affected their lateral segregation in 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayers. 28297656 1 56 theme N-linked 153:160 arg1 chain 167:171 the N-linked acyl chain 149:171 the N-linked acyl chain of ceramides 149:184 We examined how the length of the long-chain base or the N-linked acyl chain of ceramides affected their lateral segregation in 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayers. 28297656 6 57 theme sphingoid 1190:1198 arg1 base 1200:1203 a longer sphingoid base 1181:1203 a longer sphingoid base 1181:1203 Finally, we compared two ceramide analogs with equal carbon numbers (d16:1/17:0 or d20:1/13:0) and observed that the analog with a longer sphingoid base segregated at lower bilayer concentrations to a ceramide-rich phase compared with the shorter sphingoid base analog. 28297656 3 58 from d18:1 487:491 arg1 ceramide 526:533 N-palmitoyl ceramide 514:533 N-palmitoyl ceramide 514:533 The longer the length of the long-chain base (d16:1, d17:1, d18:1, d19:1, and d20:1 in N-palmitoyl ceramide), the less ceramide was needed for the onset of lateral segregation and ceramide-rich phase formation. 28297656 4 59 dep length 762:767 arg1 16:0-20:0 779:787 16:0-20:0 779:787 16:0-20:0 779:787 A similar but much weaker trend was observed when sphingosine (d18:1)-based ceramide had N-linked acyl chains of increasing length (14:0 and 16:0-20:0 in one-carbon increments). 28297656 4 59 dep length 762:767 arg1 14:0 770:773 14:0 770:773 14:0 770:773 A similar but much weaker trend was observed when sphingosine (d18:1)-based ceramide had N-linked acyl chains of increasing length (14:0 and 16:0-20:0 in one-carbon increments). 28297656 6 60 theme carbon 1105:1110 arg1 d16:1/17:0 1121:1130 d16:1/17:0 1121:1130 d16:1/17:0 1121:1130 Finally, we compared two ceramide analogs with equal carbon numbers (d16:1/17:0 or d20:1/13:0) and observed that the analog with a longer sphingoid base segregated at lower bilayer concentrations to a ceramide-rich phase compared with the shorter sphingoid base analog. 28297656 6 60 theme carbon 1105:1110 arg1 numbers 1112:1118 equal carbon numbers 1099:1118 equal carbon numbers (d16:1/17:0 or d20:1/13:0) 1099:1145 Finally, we compared two ceramide analogs with equal carbon numbers (d16:1/17:0 or d20:1/13:0) and observed that the analog with a longer sphingoid base segregated at lower bilayer concentrations to a ceramide-rich phase compared with the shorter sphingoid base analog. 28297656 6 60 theme carbon 1105:1110 arg1 d20:1/13:0 1135:1144 d20:1/13:0 1135:1144 d20:1/13:0 1135:1144 Finally, we compared two ceramide analogs with equal carbon numbers (d16:1/17:0 or d20:1/13:0) and observed that the analog with a longer sphingoid base segregated at lower bilayer concentrations to a ceramide-rich phase compared with the shorter sphingoid base analog. 28297656 4 61 contain had 723:725 arg1 ceramide 714:721 sphingosine (d18:1)-based ceramide 688:721 sphingosine (d18:1)-based ceramide 688:721 A similar but much weaker trend was observed when sphingosine (d18:1)-based ceramide had N-linked acyl chains of increasing length (14:0 and 16:0-20:0 in one-carbon increments). 28297656 4 61 contain had 723:725 arg2 chains 741:746 N-linked acyl chains 727:746 N-linked acyl chains of increasing length (14:0 and 16:0-20:0 in one-carbon increments) 727:813 A similar but much weaker trend was observed when sphingosine (d18:1)-based ceramide had N-linked acyl chains of increasing length (14:0 and 16:0-20:0 in one-carbon increments). 28297656 6 62 theme shorter 1291:1297 arg1 analog 1314:1319 the shorter sphingoid base analog 1287:1319 the shorter sphingoid base analog 1287:1319 Finally, we compared two ceramide analogs with equal carbon numbers (d16:1/17:0 or d20:1/13:0) and observed that the analog with a longer sphingoid base segregated at lower bilayer concentrations to a ceramide-rich phase compared with the shorter sphingoid base analog. 28297656 3 63 from d19:1 494:498 arg1 ceramide 526:533 N-palmitoyl ceramide 514:533 N-palmitoyl ceramide 514:533 The longer the length of the long-chain base (d16:1, d17:1, d18:1, d19:1, and d20:1 in N-palmitoyl ceramide), the less ceramide was needed for the onset of lateral segregation and ceramide-rich phase formation. 28297656 1 64 theme ceramides 176:184 arg1 chain 167:171 the N-linked acyl chain 149:171 the N-linked acyl chain of ceramides 149:184 We examined how the length of the long-chain base or the N-linked acyl chain of ceramides affected their lateral segregation in 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayers. 28297656 1 64 theme ceramides 176:184 arg1 base 141:144 the long-chain base 126:144 the long-chain base 126:144 We examined how the length of the long-chain base or the N-linked acyl chain of ceramides affected their lateral segregation in 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayers. 28297656 7 65 theme d20:1/13:0 1346:1355 arg1 ceramide 1357:1364 d20:1/13:0 ceramide 1346:1364 d20:1/13:0 ceramide 1346:1364 The gel phase formed by d20:1/13:0 ceramide also was more thermostable than the gel phase formed by d16:1/17:0 ceramide. 28297656 5 66 theme N-acyl 1031:1036 arg1 length 1044:1049 the N-acyl chain length 1027:1049 the N-acyl chain length 1027:1049 The apparent lateral packing of the ceramide-rich phase, as determined from the longest-lifetime component of tPA fluorescence, also correlated strongly with the long-chain base length, but not as strongly with the N-acyl chain length. 28297656 9 67 theme base 1648:1651 arg1 important 1680:1688 important 1680:1688 important 1680:1688 We conclude that the long-chain base length of ceramide is more important than the acyl chain length in determining the lateral segregation of the ceramide-rich gel phase and intermolecular interactions therein. 28297656 9 67 theme base 1648:1651 arg1 length 1653:1658 the long-chain base length 1633:1658 the long-chain base length of ceramide 1633:1670 We conclude that the long-chain base length of ceramide is more important than the acyl chain length in determining the lateral segregation of the ceramide-rich gel phase and intermolecular interactions therein. 28297656 7 68 theme gel 1326:1328 arg1 thermostable 1380:1391 thermostable 1380:1391 thermostable 1380:1391 The gel phase formed by d20:1/13:0 ceramide also was more thermostable than the gel phase formed by d16:1/17:0 ceramide. 28297656 7 68 theme gel 1326:1328 arg1 phase 1330:1334 The gel phase 1322:1334 The gel phase formed by d20:1/13:0 ceramide 1322:1364 The gel phase formed by d20:1/13:0 ceramide also was more thermostable than the gel phase formed by d16:1/17:0 ceramide. 28297656 5 69 dep correlated 949:958 arg1 determined 876:885 determined 876:885 determined from the longest-lifetime component of tPA fluorescence 876:941 The apparent lateral packing of the ceramide-rich phase, as determined from the longest-lifetime component of tPA fluorescence, also correlated strongly with the long-chain base length, but not as strongly with the N-acyl chain length. 28297656 1 70 from segregation 209:219 arg1 bilayers 280:287 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayers 224:287 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayers 224:287 We examined how the length of the long-chain base or the N-linked acyl chain of ceramides affected their lateral segregation in 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayers. 28297656 3 71 theme segregation 591:601 arg1 onset 574:578 the onset 570:578 the onset of lateral segregation and ceramide-rich phase formation 570:635 The longer the length of the long-chain base (d16:1, d17:1, d18:1, d19:1, and d20:1 in N-palmitoyl ceramide), the less ceramide was needed for the onset of lateral segregation and ceramide-rich phase formation. 28297656 6 72 with analog 1169:1174 arg1 base 1200:1203 a longer sphingoid base 1181:1203 a longer sphingoid base 1181:1203 Finally, we compared two ceramide analogs with equal carbon numbers (d16:1/17:0 or d20:1/13:0) and observed that the analog with a longer sphingoid base segregated at lower bilayer concentrations to a ceramide-rich phase compared with the shorter sphingoid base analog. 28297656 5 73 theme ceramide-rich 852:864 arg1 phase 866:870 the ceramide-rich phase 848:870 the ceramide-rich phase 848:870 The apparent lateral packing of the ceramide-rich phase, as determined from the longest-lifetime component of tPA fluorescence, also correlated strongly with the long-chain base length, but not as strongly with the N-acyl chain length. 28297656 1 74 theme long-chain 130:139 arg1 base 141:144 the long-chain base 126:144 the long-chain base 126:144 We examined how the length of the long-chain base or the N-linked acyl chain of ceramides affected their lateral segregation in 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayers. 28297656 8 75 theme NMR 1446:1448 arg1 data 1450:1453 2H NMR data 1443:1453 2H NMR data for 10 mol % stearoyl ceramide in POPC 1443:1492 2H NMR data for 10 mol % stearoyl ceramide in POPC also showed that the long-chain base was more ordered than the acyl chain at comparable chain positions and temperatures. 28297656 4 76 theme weaker 657:662 arg1 trend 664:668 A similar but much weaker trend 638:668 A similar but much weaker trend 638:668 A similar but much weaker trend was observed when sphingosine (d18:1)-based ceramide had N-linked acyl chains of increasing length (14:0 and 16:0-20:0 in one-carbon increments). 28297656 5 77 theme phase 866:870 arg1 packing 837:843 The apparent lateral packing 816:843 The apparent lateral packing of the ceramide-rich phase 816:870 The apparent lateral packing of the ceramide-rich phase, as determined from the longest-lifetime component of tPA fluorescence, also correlated strongly with the long-chain base length, but not as strongly with the N-acyl chain length. 28297656 5 78 theme fluorescence 930:941 arg1 component 913:921 the longest-lifetime component 892:921 the longest-lifetime component of tPA fluorescence 892:941 The apparent lateral packing of the ceramide-rich phase, as determined from the longest-lifetime component of tPA fluorescence, also correlated strongly with the long-chain base length, but not as strongly with the N-acyl chain length. 28297656 2 79 theme phase 328:332 arg1 formation 334:342 ceramide-rich phase formation 314:342 ceramide-rich phase formation 314:342 Lateral segregation and ceramide-rich phase formation was ascertained by a lifetime analysis of trans-parinaric acid (tPA) fluorescence. 28297656 9 80 theme chain 1704:1708 arg1 length 1710:1715 the acyl chain length 1695:1715 the acyl chain length in determining the lateral segregation of the ceramide-rich gel phase and intermolecular interactions therein 1695:1825 We conclude that the long-chain base length of ceramide is more important than the acyl chain length in determining the lateral segregation of the ceramide-rich gel phase and intermolecular interactions therein. 28297656 8 81 theme % 1466:1466 arg1 ceramide 1477:1484 10 mol % stearoyl ceramide 1459:1484 10 mol % stearoyl ceramide in POPC 1459:1492 2H NMR data for 10 mol % stearoyl ceramide in POPC also showed that the long-chain base was more ordered than the acyl chain at comparable chain positions and temperatures. 28297656 4 82 theme N-linked 727:734 arg1 chains 741:746 N-linked acyl chains 727:746 N-linked acyl chains of increasing length (14:0 and 16:0-20:0 in one-carbon increments) 727:813 A similar but much weaker trend was observed when sphingosine (d18:1)-based ceramide had N-linked acyl chains of increasing length (14:0 and 16:0-20:0 in one-carbon increments). 28297656 6 83 theme base 1309:1312 arg1 analog 1314:1319 the shorter sphingoid base analog 1287:1319 the shorter sphingoid base analog 1287:1319 Finally, we compared two ceramide analogs with equal carbon numbers (d16:1/17:0 or d20:1/13:0) and observed that the analog with a longer sphingoid base segregated at lower bilayer concentrations to a ceramide-rich phase compared with the shorter sphingoid base analog. 28297656 3 84 dep longer 431:436 arg1 length 442:447 the length 438:447 The longer the length of the long-chain base (d16:1, d17:1, d18:1, d19:1, and d20:1 in N-palmitoyl ceramide), the less ceramide 427:553 The longer the length of the long-chain base (d16:1, d17:1, d18:1, d19:1, and d20:1 in N-palmitoyl ceramide), the less ceramide was needed for the onset of lateral segregation and ceramide-rich phase formation. 28297656 2 85 theme fluorescence 413:424 arg1 analysis 374:381 a lifetime analysis 363:381 a lifetime analysis of trans-parinaric acid (tPA) fluorescence 363:424 Lateral segregation and ceramide-rich phase formation was ascertained by a lifetime analysis of trans-parinaric acid (tPA) fluorescence. 28297656 0 86 theme Long-Chain 4:13 arg1 Base 25:28 The Long-Chain Sphingoid Base 0:28 The Long-Chain Sphingoid Base of Ceramides 0:41 The Long-Chain Sphingoid Base of Ceramides Determines Their Propensity for Lateral Segregation. 28297656 5 87 theme longest-lifetime 896:911 arg1 component 913:921 the longest-lifetime component 892:921 the longest-lifetime component of tPA fluorescence 892:941 The apparent lateral packing of the ceramide-rich phase, as determined from the longest-lifetime component of tPA fluorescence, also correlated strongly with the long-chain base length, but not as strongly with the N-acyl chain length. 28297656 3 88 theme formation 627:635 arg1 onset 574:578 the onset 570:578 the onset of lateral segregation and ceramide-rich phase formation 570:635 The longer the length of the long-chain base (d16:1, d17:1, d18:1, d19:1, and d20:1 in N-palmitoyl ceramide), the less ceramide was needed for the onset of lateral segregation and ceramide-rich phase formation. 28297656 8 89 from ceramide 1477:1484 arg1 POPC 1489:1492 POPC 1489:1492 POPC 1489:1492 2H NMR data for 10 mol % stearoyl ceramide in POPC also showed that the long-chain base was more ordered than the acyl chain at comparable chain positions and temperatures. 28297656 5 90 theme base 989:992 arg1 length 994:999 the long-chain base length 974:999 the long-chain base length 974:999 The apparent lateral packing of the ceramide-rich phase, as determined from the longest-lifetime component of tPA fluorescence, also correlated strongly with the long-chain base length, but not as strongly with the N-acyl chain length. 28297656 3 91 theme ceramide-rich 607:619 arg1 formation 627:635 ceramide-rich phase formation 607:635 ceramide-rich phase formation 607:635 The longer the length of the long-chain base (d16:1, d17:1, d18:1, d19:1, and d20:1 in N-palmitoyl ceramide), the less ceramide was needed for the onset of lateral segregation and ceramide-rich phase formation. 28297656 9 92 theme gel 1777:1779 arg1 phase 1781:1785 the ceramide-rich gel phase 1759:1785 the ceramide-rich gel phase 1759:1785 We conclude that the long-chain base length of ceramide is more important than the acyl chain length in determining the lateral segregation of the ceramide-rich gel phase and intermolecular interactions therein. 28297656 2 93 theme lifetime 365:372 arg1 analysis 374:381 a lifetime analysis 363:381 a lifetime analysis of trans-parinaric acid (tPA) fluorescence 363:424 Lateral segregation and ceramide-rich phase formation was ascertained by a lifetime analysis of trans-parinaric acid (tPA) fluorescence. 28297656 8 94 theme chain 1582:1586 arg1 positions 1588:1596 comparable chain positions 1571:1596 comparable chain positions 1571:1596 2H NMR data for 10 mol % stearoyl ceramide in POPC also showed that the long-chain base was more ordered than the acyl chain at comparable chain positions and temperatures. 28297656 9 95 theme interactions 1806:1817 arg1 segregation 1744:1754 the lateral segregation 1732:1754 the lateral segregation of the ceramide-rich gel phase and intermolecular interactions therein 1732:1825 We conclude that the long-chain base length of ceramide is more important than the acyl chain length in determining the lateral segregation of the ceramide-rich gel phase and intermolecular interactions therein. 28297656 2 96 theme acid 402:405 arg1 fluorescence 413:424 trans-parinaric acid (tPA) fluorescence 386:424 trans-parinaric acid (tPA) fluorescence 386:424 Lateral segregation and ceramide-rich phase formation was ascertained by a lifetime analysis of trans-parinaric acid (tPA) fluorescence. 28760965 2 0 from acids 517:521 arg1 SILAC 540:544 SILAC 540:544 SILAC 540:544 To analyze the turnover dynamics of O-GlcNAcylated proteins, we developed a quantitative time-resolved O-linked GlcNAc proteomics (qTOP) strategy based on metabolic pulse-chase labeling with an O-GlcNAc chemical reporter and stable isotope labeling with amino acids in cell culture (SILAC). 28760965 2 0 from acids 517:521 arg1 culture 531:537 cell culture 526:537 cell culture (SILAC) 526:545 To analyze the turnover dynamics of O-GlcNAcylated proteins, we developed a quantitative time-resolved O-linked GlcNAc proteomics (qTOP) strategy based on metabolic pulse-chase labeling with an O-GlcNAc chemical reporter and stable isotope labeling with amino acids in cell culture (SILAC). 28760965 7 1 theme rRNAs 1267:1271 arg1 2'-O-methylation 1247:1262 the 2'-O-methylation 1243:1262 the 2'-O-methylation of rRNAs 1243:1271 Blocking O-GlcNAcylation on FBL altered the 2'-O-methylation of rRNAs and impaired cancer cell proliferation and tumor formation in vivo. 28760965 2 2 theme cell 526:529 arg1 SILAC 540:544 SILAC 540:544 SILAC 540:544 To analyze the turnover dynamics of O-GlcNAcylated proteins, we developed a quantitative time-resolved O-linked GlcNAc proteomics (qTOP) strategy based on metabolic pulse-chase labeling with an O-GlcNAc chemical reporter and stable isotope labeling with amino acids in cell culture (SILAC). 28760965 2 2 theme cell 526:529 arg1 culture 531:537 cell culture 526:537 cell culture (SILAC) 526:545 To analyze the turnover dynamics of O-GlcNAcylated proteins, we developed a quantitative time-resolved O-linked GlcNAc proteomics (qTOP) strategy based on metabolic pulse-chase labeling with an O-GlcNAc chemical reporter and stable isotope labeling with amino acids in cell culture (SILAC). 28760965 3 3 theme O-GlcNAc 703:710 arg1 degradation 715:725 degradation 715:725 degradation of protein backbones 715:746 Applying qTOP, we quantified the turnover rates of 533 O-GlcNAcylated proteins in NIH 3T3 cells and discovered that about 14% exhibited minimal removal of O-GlcNAc or degradation of protein backbones. 28760965 3 3 theme O-GlcNAc 703:710 arg1 removal 692:698 minimal removal 684:698 minimal removal of O-GlcNAc 684:710 Applying qTOP, we quantified the turnover rates of 533 O-GlcNAcylated proteins in NIH 3T3 cells and discovered that about 14% exhibited minimal removal of O-GlcNAc or degradation of protein backbones. 28760965 1 4 from modification 182:193 arg1 proteins 212:219 intracellular proteins 198:219 intracellular proteins 198:219 O-linked GlcNAcylation (O-GlcNAcylation), a ubiquitous posttranslational modification on intracellular proteins, is dynamically regulated in cells. 28760965 5 5 theme core 945:948 arg1 proteins 950:957 three core proteins 939:957 three core proteins of box C/D small nucleolar ribonucleoprotein complexes (snoRNPs): fibrillarin (FBL), nucleolar protein 5A (NOP56), and nucleolar protein 5 (NOP58) 939:1104 Among the hyperstable population were three core proteins of box C/D small nucleolar ribonucleoprotein complexes (snoRNPs): fibrillarin (FBL), nucleolar protein 5A (NOP56), and nucleolar protein 5 (NOP58). 28760965 2 6 with labeling 434:441 arg1 acids 517:521 amino acids 511:521 amino acids in cell culture (SILAC) 511:545 To analyze the turnover dynamics of O-GlcNAcylated proteins, we developed a quantitative time-resolved O-linked GlcNAc proteomics (qTOP) strategy based on metabolic pulse-chase labeling with an O-GlcNAc chemical reporter and stable isotope labeling with amino acids in cell culture (SILAC). 28760965 2 6 with labeling 434:441 arg1 reporter 469:476 an O-GlcNAc chemical reporter 448:476 an O-GlcNAc chemical reporter 448:476 To analyze the turnover dynamics of O-GlcNAcylated proteins, we developed a quantitative time-resolved O-linked GlcNAc proteomics (qTOP) strategy based on metabolic pulse-chase labeling with an O-GlcNAc chemical reporter and stable isotope labeling with amino acids in cell culture (SILAC). 28760965 4 7 theme proteins 799:806 arg1 stability 753:761 The stability 749:761 The stability of those hyperstable O-GlcNAcylated proteins 749:806 The stability of those hyperstable O-GlcNAcylated proteins was more sensitive to O-GlcNAcylation inhibition compared with the more dynamic populations. 28760965 4 7 theme proteins 799:806 arg1 sensitive 817:825 sensitive 817:825 sensitive 817:825 The stability of those hyperstable O-GlcNAcylated proteins was more sensitive to O-GlcNAcylation inhibition compared with the more dynamic populations. 28760965 5 8 theme ribonucleoprotein 986:1002 arg1 snoRNPs 1015:1021 snoRNPs 1015:1021 snoRNPs 1015:1021 Among the hyperstable population were three core proteins of box C/D small nucleolar ribonucleoprotein complexes (snoRNPs): fibrillarin (FBL), nucleolar protein 5A (NOP56), and nucleolar protein 5 (NOP58). 28760965 5 8 theme ribonucleoprotein 986:1002 arg1 complexes 1004:1012 small nucleolar ribonucleoprotein complexes 970:1012 small nucleolar ribonucleoprotein complexes (snoRNPs) 970:1022 Among the hyperstable population were three core proteins of box C/D small nucleolar ribonucleoprotein complexes (snoRNPs): fibrillarin (FBL), nucleolar protein 5A (NOP56), and nucleolar protein 5 (NOP58). 28760965 4 9 theme O-GlcNAcylated 784:797 arg1 proteins 799:806 those hyperstable O-GlcNAcylated proteins 766:806 those hyperstable O-GlcNAcylated proteins 766:806 The stability of those hyperstable O-GlcNAcylated proteins was more sensitive to O-GlcNAcylation inhibition compared with the more dynamic populations. 28760965 0 10 theme Quantitative 0:11 arg1 chemoproteomics 27:41 Quantitative time-resolved chemoproteomics 0:41 Quantitative time-resolved chemoproteomics 0:41 Quantitative time-resolved chemoproteomics reveals that stable O-GlcNAc regulates box C/D snoRNP biogenesis. 28760965 5 11 theme nucleolar 976:984 arg1 snoRNPs 1015:1021 snoRNPs 1015:1021 snoRNPs 1015:1021 Among the hyperstable population were three core proteins of box C/D small nucleolar ribonucleoprotein complexes (snoRNPs): fibrillarin (FBL), nucleolar protein 5A (NOP56), and nucleolar protein 5 (NOP58). 28760965 5 11 theme nucleolar 976:984 arg1 complexes 1004:1012 small nucleolar ribonucleoprotein complexes 970:1012 small nucleolar ribonucleoprotein complexes (snoRNPs) 970:1022 Among the hyperstable population were three core proteins of box C/D small nucleolar ribonucleoprotein complexes (snoRNPs): fibrillarin (FBL), nucleolar protein 5A (NOP56), and nucleolar protein 5 (NOP58). 28760965 7 12 theme Blocking 1203:1210 arg1 O-GlcNAcylation 1212:1226 Blocking O-GlcNAcylation 1203:1226 Blocking O-GlcNAcylation on FBL 1203:1233 Blocking O-GlcNAcylation on FBL altered the 2'-O-methylation of rRNAs and impaired cancer cell proliferation and tumor formation in vivo. 28760965 5 13 theme box 962:964 arg1 C/D 966:968 box C/D 962:968 box C/D 962:968 Among the hyperstable population were three core proteins of box C/D small nucleolar ribonucleoprotein complexes (snoRNPs): fibrillarin (FBL), nucleolar protein 5A (NOP56), and nucleolar protein 5 (NOP58). 28760965 5 14 theme fibrillarin 1025:1035 arg1 proteins 950:957 three core proteins 939:957 three core proteins of box C/D small nucleolar ribonucleoprotein complexes (snoRNPs): fibrillarin (FBL), nucleolar protein 5A (NOP56), and nucleolar protein 5 (NOP58) 939:1104 Among the hyperstable population were three core proteins of box C/D small nucleolar ribonucleoprotein complexes (snoRNPs): fibrillarin (FBL), nucleolar protein 5A (NOP56), and nucleolar protein 5 (NOP58). 28760965 1 15 theme intracellular 198:210 arg1 proteins 212:219 intracellular proteins 198:219 intracellular proteins 198:219 O-linked GlcNAcylation (O-GlcNAcylation), a ubiquitous posttranslational modification on intracellular proteins, is dynamically regulated in cells. 28760965 1 16 gly GlcNAcylation 118:130 arg1 cells 250:254 cells 250:254 cells 250:254 O-linked GlcNAcylation (O-GlcNAcylation), a ubiquitous posttranslational modification on intracellular proteins, is dynamically regulated in cells. 28760965 3 17 theme protein 730:736 arg1 backbones 738:746 protein backbones 730:746 protein backbones 730:746 Applying qTOP, we quantified the turnover rates of 533 O-GlcNAcylated proteins in NIH 3T3 cells and discovered that about 14% exhibited minimal removal of O-GlcNAc or degradation of protein backbones. 28760965 4 18 theme dynamic 880:886 arg1 populations 888:898 the more dynamic populations 871:898 the more dynamic populations 871:898 The stability of those hyperstable O-GlcNAcylated proteins was more sensitive to O-GlcNAcylation inhibition compared with the more dynamic populations. 28760965 2 19 theme proteins 308:315 arg1 dynamics 281:288 the turnover dynamics 268:288 the turnover dynamics of O-GlcNAcylated proteins 268:315 To analyze the turnover dynamics of O-GlcNAcylated proteins, we developed a quantitative time-resolved O-linked GlcNAc proteomics (qTOP) strategy based on metabolic pulse-chase labeling with an O-GlcNAc chemical reporter and stable isotope labeling with amino acids in cell culture (SILAC). 28760965 5 20 theme hyperstable 911:921 arg1 population 923:932 the hyperstable population 907:932 the hyperstable population 907:932 Among the hyperstable population were three core proteins of box C/D small nucleolar ribonucleoprotein complexes (snoRNPs): fibrillarin (FBL), nucleolar protein 5A (NOP56), and nucleolar protein 5 (NOP58). 28760965 0 21 theme time-resolved 13:25 arg1 chemoproteomics 27:41 Quantitative time-resolved chemoproteomics 0:41 Quantitative time-resolved chemoproteomics 0:41 Quantitative time-resolved chemoproteomics reveals that stable O-GlcNAc regulates box C/D snoRNP biogenesis. 28760965 0 22 theme snoRNP 90:95 arg1 biogenesis 97:106 box C/D snoRNP biogenesis 82:106 box C/D snoRNP biogenesis 82:106 Quantitative time-resolved chemoproteomics reveals that stable O-GlcNAc regulates box C/D snoRNP biogenesis. 28760965 7 23 theme cancer 1286:1291 arg1 proliferation 1298:1310 cancer cell proliferation 1286:1310 cancer cell proliferation 1286:1310 Blocking O-GlcNAcylation on FBL altered the 2'-O-methylation of rRNAs and impaired cancer cell proliferation and tumor formation in vivo. 28760965 2 24 theme O-linked 360:367 arg1 strategy 394:401 a quantitative time-resolved O-linked GlcNAc proteomics (qTOP) strategy 331:401 a quantitative time-resolved O-linked GlcNAc proteomics (qTOP) strategy based on metabolic pulse-chase labeling with an O-GlcNAc chemical reporter and stable isotope labeling with amino acids in cell culture (SILAC) 331:545 To analyze the turnover dynamics of O-GlcNAcylated proteins, we developed a quantitative time-resolved O-linked GlcNAc proteomics (qTOP) strategy based on metabolic pulse-chase labeling with an O-GlcNAc chemical reporter and stable isotope labeling with amino acids in cell culture (SILAC). 28760965 2 25 theme pulse-chase 422:432 arg1 labeling 434:441 metabolic pulse-chase labeling 412:441 metabolic pulse-chase labeling with an O-GlcNAc chemical reporter 412:476 To analyze the turnover dynamics of O-GlcNAcylated proteins, we developed a quantitative time-resolved O-linked GlcNAc proteomics (qTOP) strategy based on metabolic pulse-chase labeling with an O-GlcNAc chemical reporter and stable isotope labeling with amino acids in cell culture (SILAC). 28760965 2 26 theme isotope 489:495 arg1 labeling 497:504 stable isotope labeling 482:504 stable isotope labeling with amino acids in cell culture (SILAC) 482:545 To analyze the turnover dynamics of O-GlcNAcylated proteins, we developed a quantitative time-resolved O-linked GlcNAc proteomics (qTOP) strategy based on metabolic pulse-chase labeling with an O-GlcNAc chemical reporter and stable isotope labeling with amino acids in cell culture (SILAC). 28760965 5 27 theme nucleolar 1078:1086 arg1 protein 1088:1094 nucleolar protein 5 1078:1096 nucleolar protein 5 (NOP58) 1078:1104 Among the hyperstable population were three core proteins of box C/D small nucleolar ribonucleoprotein complexes (snoRNPs): fibrillarin (FBL), nucleolar protein 5A (NOP56), and nucleolar protein 5 (NOP58). 28760965 5 27 theme nucleolar 1078:1086 arg1 NOP58 1099:1103 NOP58 1099:1103 NOP58 1099:1103 Among the hyperstable population were three core proteins of box C/D small nucleolar ribonucleoprotein complexes (snoRNPs): fibrillarin (FBL), nucleolar protein 5A (NOP56), and nucleolar protein 5 (NOP58). 28760965 1 28 theme O-linked 109:116 arg1 modification 182:193 a ubiquitous posttranslational modification 151:193 a ubiquitous posttranslational modification on intracellular proteins 151:219 O-linked GlcNAcylation (O-GlcNAcylation), a ubiquitous posttranslational modification on intracellular proteins, is dynamically regulated in cells. 28760965 1 28 theme O-linked 109:116 arg1 O-GlcNAcylation 133:147 O-GlcNAcylation 133:147 O-GlcNAcylation 133:147 O-linked GlcNAcylation (O-GlcNAcylation), a ubiquitous posttranslational modification on intracellular proteins, is dynamically regulated in cells. 28760965 1 28 theme O-linked 109:116 arg1 GlcNAcylation 118:130 O-linked GlcNAcylation 109:130 O-linked GlcNAcylation (O-GlcNAcylation) 109:148 O-linked GlcNAcylation (O-GlcNAcylation), a ubiquitous posttranslational modification on intracellular proteins, is dynamically regulated in cells. 28760965 2 29 theme metabolic 412:420 arg1 labeling 434:441 metabolic pulse-chase labeling 412:441 metabolic pulse-chase labeling with an O-GlcNAc chemical reporter 412:476 To analyze the turnover dynamics of O-GlcNAcylated proteins, we developed a quantitative time-resolved O-linked GlcNAc proteomics (qTOP) strategy based on metabolic pulse-chase labeling with an O-GlcNAc chemical reporter and stable isotope labeling with amino acids in cell culture (SILAC). 28760965 2 30 theme stable 482:487 arg1 labeling 497:504 stable isotope labeling 482:504 stable isotope labeling with amino acids in cell culture (SILAC) 482:545 To analyze the turnover dynamics of O-GlcNAcylated proteins, we developed a quantitative time-resolved O-linked GlcNAc proteomics (qTOP) strategy based on metabolic pulse-chase labeling with an O-GlcNAc chemical reporter and stable isotope labeling with amino acids in cell culture (SILAC). 28760965 3 31 theme backbones 738:746 arg1 degradation 715:725 degradation 715:725 degradation of protein backbones 715:746 Applying qTOP, we quantified the turnover rates of 533 O-GlcNAcylated proteins in NIH 3T3 cells and discovered that about 14% exhibited minimal removal of O-GlcNAc or degradation of protein backbones. 28760965 3 31 theme backbones 738:746 arg1 removal 692:698 minimal removal 684:698 minimal removal of O-GlcNAc 684:710 Applying qTOP, we quantified the turnover rates of 533 O-GlcNAcylated proteins in NIH 3T3 cells and discovered that about 14% exhibited minimal removal of O-GlcNAc or degradation of protein backbones. 28760965 2 32 theme quantitative 333:344 arg1 strategy 394:401 a quantitative time-resolved O-linked GlcNAc proteomics (qTOP) strategy 331:401 a quantitative time-resolved O-linked GlcNAc proteomics (qTOP) strategy based on metabolic pulse-chase labeling with an O-GlcNAc chemical reporter and stable isotope labeling with amino acids in cell culture (SILAC) 331:545 To analyze the turnover dynamics of O-GlcNAcylated proteins, we developed a quantitative time-resolved O-linked GlcNAc proteomics (qTOP) strategy based on metabolic pulse-chase labeling with an O-GlcNAc chemical reporter and stable isotope labeling with amino acids in cell culture (SILAC). 28760965 2 33 theme time-resolved 346:358 arg1 strategy 394:401 a quantitative time-resolved O-linked GlcNAc proteomics (qTOP) strategy 331:401 a quantitative time-resolved O-linked GlcNAc proteomics (qTOP) strategy based on metabolic pulse-chase labeling with an O-GlcNAc chemical reporter and stable isotope labeling with amino acids in cell culture (SILAC) 331:545 To analyze the turnover dynamics of O-GlcNAcylated proteins, we developed a quantitative time-resolved O-linked GlcNAc proteomics (qTOP) strategy based on metabolic pulse-chase labeling with an O-GlcNAc chemical reporter and stable isotope labeling with amino acids in cell culture (SILAC). 28760965 6 34 theme snoRNP 1186:1191 arg1 assembly 1193:1200 snoRNP assembly 1186:1200 snoRNP assembly 1186:1200 We showed that O-GlcNAcylation stabilized these proteins and was essential for snoRNP assembly. 28760965 5 35 theme protein 1088:1094 arg1 proteins 950:957 three core proteins 939:957 three core proteins of box C/D small nucleolar ribonucleoprotein complexes (snoRNPs): fibrillarin (FBL), nucleolar protein 5A (NOP56), and nucleolar protein 5 (NOP58) 939:1104 Among the hyperstable population were three core proteins of box C/D small nucleolar ribonucleoprotein complexes (snoRNPs): fibrillarin (FBL), nucleolar protein 5A (NOP56), and nucleolar protein 5 (NOP58). 28760965 2 36 theme chemical 460:467 arg1 reporter 469:476 an O-GlcNAc chemical reporter 448:476 an O-GlcNAc chemical reporter 448:476 To analyze the turnover dynamics of O-GlcNAcylated proteins, we developed a quantitative time-resolved O-linked GlcNAc proteomics (qTOP) strategy based on metabolic pulse-chase labeling with an O-GlcNAc chemical reporter and stable isotope labeling with amino acids in cell culture (SILAC). 28760965 0 37 theme stable 56:61 arg1 O-GlcNAc 63:70 stable O-GlcNAc 56:70 stable O-GlcNAc 56:70 Quantitative time-resolved chemoproteomics reveals that stable O-GlcNAc regulates box C/D snoRNP biogenesis. 28760965 5 38 theme nucleolar 1044:1052 arg1 5A 1062:1063 nucleolar protein 5A 1044:1063 nucleolar protein 5A (NOP56) 1044:1071 Among the hyperstable population were three core proteins of box C/D small nucleolar ribonucleoprotein complexes (snoRNPs): fibrillarin (FBL), nucleolar protein 5A (NOP56), and nucleolar protein 5 (NOP58). 28760965 5 38 theme nucleolar 1044:1052 arg1 NOP56 1066:1070 NOP56 1066:1070 NOP56 1066:1070 Among the hyperstable population were three core proteins of box C/D small nucleolar ribonucleoprotein complexes (snoRNPs): fibrillarin (FBL), nucleolar protein 5A (NOP56), and nucleolar protein 5 (NOP58). 28760965 7 39 from O-GlcNAcylation 1212:1226 arg1 FBL 1231:1233 FBL 1231:1233 FBL 1231:1233 Blocking O-GlcNAcylation on FBL altered the 2'-O-methylation of rRNAs and impaired cancer cell proliferation and tumor formation in vivo. 28760965 5 40 theme protein 1054:1060 arg1 5A 1062:1063 nucleolar protein 5A 1044:1063 nucleolar protein 5A (NOP56) 1044:1071 Among the hyperstable population were three core proteins of box C/D small nucleolar ribonucleoprotein complexes (snoRNPs): fibrillarin (FBL), nucleolar protein 5A (NOP56), and nucleolar protein 5 (NOP58). 28760965 5 40 theme protein 1054:1060 arg1 NOP56 1066:1070 NOP56 1066:1070 NOP56 1066:1070 Among the hyperstable population were three core proteins of box C/D small nucleolar ribonucleoprotein complexes (snoRNPs): fibrillarin (FBL), nucleolar protein 5A (NOP56), and nucleolar protein 5 (NOP58). 28760965 2 41 theme O-GlcNAc 451:458 arg1 reporter 469:476 an O-GlcNAc chemical reporter 448:476 an O-GlcNAc chemical reporter 448:476 To analyze the turnover dynamics of O-GlcNAcylated proteins, we developed a quantitative time-resolved O-linked GlcNAc proteomics (qTOP) strategy based on metabolic pulse-chase labeling with an O-GlcNAc chemical reporter and stable isotope labeling with amino acids in cell culture (SILAC). 28760965 3 42 theme NIH 630:632 arg1 cells 638:642 NIH 3T3 cells 630:642 NIH 3T3 cells 630:642 Applying qTOP, we quantified the turnover rates of 533 O-GlcNAcylated proteins in NIH 3T3 cells and discovered that about 14% exhibited minimal removal of O-GlcNAc or degradation of protein backbones. 28760965 4 43 theme hyperstable 772:782 arg1 proteins 799:806 those hyperstable O-GlcNAcylated proteins 766:806 those hyperstable O-GlcNAcylated proteins 766:806 The stability of those hyperstable O-GlcNAcylated proteins was more sensitive to O-GlcNAcylation inhibition compared with the more dynamic populations. 28760965 2 44 theme amino 511:515 arg1 acids 517:521 amino acids 511:521 amino acids in cell culture (SILAC) 511:545 To analyze the turnover dynamics of O-GlcNAcylated proteins, we developed a quantitative time-resolved O-linked GlcNAc proteomics (qTOP) strategy based on metabolic pulse-chase labeling with an O-GlcNAc chemical reporter and stable isotope labeling with amino acids in cell culture (SILAC). 28760965 3 45 theme O-GlcNAcylated 603:616 arg1 proteins 618:625 533 O-GlcNAcylated proteins 599:625 533 O-GlcNAcylated proteins 599:625 Applying qTOP, we quantified the turnover rates of 533 O-GlcNAcylated proteins in NIH 3T3 cells and discovered that about 14% exhibited minimal removal of O-GlcNAc or degradation of protein backbones. 28760965 2 46 theme qTOP 388:391 arg1 strategy 394:401 a quantitative time-resolved O-linked GlcNAc proteomics (qTOP) strategy 331:401 a quantitative time-resolved O-linked GlcNAc proteomics (qTOP) strategy based on metabolic pulse-chase labeling with an O-GlcNAc chemical reporter and stable isotope labeling with amino acids in cell culture (SILAC) 331:545 To analyze the turnover dynamics of O-GlcNAcylated proteins, we developed a quantitative time-resolved O-linked GlcNAc proteomics (qTOP) strategy based on metabolic pulse-chase labeling with an O-GlcNAc chemical reporter and stable isotope labeling with amino acids in cell culture (SILAC). 28760965 2 47 link O-linked 360:367 arg1 strategy 394:401 a quantitative time-resolved O-linked GlcNAc proteomics (qTOP) strategy 331:401 a quantitative time-resolved O-linked GlcNAc proteomics (qTOP) strategy based on metabolic pulse-chase labeling with an O-GlcNAc chemical reporter and stable isotope labeling with amino acids in cell culture (SILAC) 331:545 To analyze the turnover dynamics of O-GlcNAcylated proteins, we developed a quantitative time-resolved O-linked GlcNAc proteomics (qTOP) strategy based on metabolic pulse-chase labeling with an O-GlcNAc chemical reporter and stable isotope labeling with amino acids in cell culture (SILAC). 28760965 3 48 theme proteins 618:625 arg1 rates 590:594 the turnover rates 577:594 the turnover rates of 533 O-GlcNAcylated proteins in NIH 3T3 cells 577:642 Applying qTOP, we quantified the turnover rates of 533 O-GlcNAcylated proteins in NIH 3T3 cells and discovered that about 14% exhibited minimal removal of O-GlcNAc or degradation of protein backbones. 28760965 2 49 with labeling 497:504 arg1 acids 517:521 amino acids 511:521 amino acids in cell culture (SILAC) 511:545 To analyze the turnover dynamics of O-GlcNAcylated proteins, we developed a quantitative time-resolved O-linked GlcNAc proteomics (qTOP) strategy based on metabolic pulse-chase labeling with an O-GlcNAc chemical reporter and stable isotope labeling with amino acids in cell culture (SILAC). 28760965 2 49 with labeling 497:504 arg1 reporter 469:476 an O-GlcNAc chemical reporter 448:476 an O-GlcNAc chemical reporter 448:476 To analyze the turnover dynamics of O-GlcNAcylated proteins, we developed a quantitative time-resolved O-linked GlcNAc proteomics (qTOP) strategy based on metabolic pulse-chase labeling with an O-GlcNAc chemical reporter and stable isotope labeling with amino acids in cell culture (SILAC). 28760965 5 50 theme C/D 966:968 arg1 proteins 950:957 three core proteins 939:957 three core proteins of box C/D small nucleolar ribonucleoprotein complexes (snoRNPs): fibrillarin (FBL), nucleolar protein 5A (NOP56), and nucleolar protein 5 (NOP58) 939:1104 Among the hyperstable population were three core proteins of box C/D small nucleolar ribonucleoprotein complexes (snoRNPs): fibrillarin (FBL), nucleolar protein 5A (NOP56), and nucleolar protein 5 (NOP58). 28760965 4 51 theme O-GlcNAcylation 830:844 arg1 inhibition 846:855 O-GlcNAcylation inhibition 830:855 O-GlcNAcylation inhibition 830:855 The stability of those hyperstable O-GlcNAcylated proteins was more sensitive to O-GlcNAcylation inhibition compared with the more dynamic populations. 28760965 2 52 theme O-GlcNAcylated 293:306 arg1 proteins 308:315 O-GlcNAcylated proteins 293:315 O-GlcNAcylated proteins 293:315 To analyze the turnover dynamics of O-GlcNAcylated proteins, we developed a quantitative time-resolved O-linked GlcNAc proteomics (qTOP) strategy based on metabolic pulse-chase labeling with an O-GlcNAc chemical reporter and stable isotope labeling with amino acids in cell culture (SILAC). 28760965 5 53 theme 5A 1062:1063 arg1 proteins 950:957 three core proteins 939:957 three core proteins of box C/D small nucleolar ribonucleoprotein complexes (snoRNPs): fibrillarin (FBL), nucleolar protein 5A (NOP56), and nucleolar protein 5 (NOP58) 939:1104 Among the hyperstable population were three core proteins of box C/D small nucleolar ribonucleoprotein complexes (snoRNPs): fibrillarin (FBL), nucleolar protein 5A (NOP56), and nucleolar protein 5 (NOP58). 28760965 2 54 theme proteomics 376:385 arg1 strategy 394:401 a quantitative time-resolved O-linked GlcNAc proteomics (qTOP) strategy 331:401 a quantitative time-resolved O-linked GlcNAc proteomics (qTOP) strategy based on metabolic pulse-chase labeling with an O-GlcNAc chemical reporter and stable isotope labeling with amino acids in cell culture (SILAC) 331:545 To analyze the turnover dynamics of O-GlcNAcylated proteins, we developed a quantitative time-resolved O-linked GlcNAc proteomics (qTOP) strategy based on metabolic pulse-chase labeling with an O-GlcNAc chemical reporter and stable isotope labeling with amino acids in cell culture (SILAC). 28760965 3 55 theme turnover 581:588 arg1 rates 590:594 the turnover rates 577:594 the turnover rates of 533 O-GlcNAcylated proteins in NIH 3T3 cells 577:642 Applying qTOP, we quantified the turnover rates of 533 O-GlcNAcylated proteins in NIH 3T3 cells and discovered that about 14% exhibited minimal removal of O-GlcNAc or degradation of protein backbones. 28760965 5 56 dep C/D 966:968 arg1 snoRNPs 1015:1021 snoRNPs 1015:1021 snoRNPs 1015:1021 Among the hyperstable population were three core proteins of box C/D small nucleolar ribonucleoprotein complexes (snoRNPs): fibrillarin (FBL), nucleolar protein 5A (NOP56), and nucleolar protein 5 (NOP58). 28760965 5 56 dep C/D 966:968 arg1 complexes 1004:1012 small nucleolar ribonucleoprotein complexes 970:1012 small nucleolar ribonucleoprotein complexes (snoRNPs) 970:1022 Among the hyperstable population were three core proteins of box C/D small nucleolar ribonucleoprotein complexes (snoRNPs): fibrillarin (FBL), nucleolar protein 5A (NOP56), and nucleolar protein 5 (NOP58). 28760965 7 57 theme tumor 1316:1320 arg1 formation 1322:1330 tumor formation 1316:1330 tumor formation in vivo 1316:1338 Blocking O-GlcNAcylation on FBL altered the 2'-O-methylation of rRNAs and impaired cancer cell proliferation and tumor formation in vivo. 28760965 2 58 theme GlcNAc 369:374 arg1 strategy 394:401 a quantitative time-resolved O-linked GlcNAc proteomics (qTOP) strategy 331:401 a quantitative time-resolved O-linked GlcNAc proteomics (qTOP) strategy based on metabolic pulse-chase labeling with an O-GlcNAc chemical reporter and stable isotope labeling with amino acids in cell culture (SILAC) 331:545 To analyze the turnover dynamics of O-GlcNAcylated proteins, we developed a quantitative time-resolved O-linked GlcNAc proteomics (qTOP) strategy based on metabolic pulse-chase labeling with an O-GlcNAc chemical reporter and stable isotope labeling with amino acids in cell culture (SILAC). 28760965 5 59 theme small 970:974 arg1 snoRNPs 1015:1021 snoRNPs 1015:1021 snoRNPs 1015:1021 Among the hyperstable population were three core proteins of box C/D small nucleolar ribonucleoprotein complexes (snoRNPs): fibrillarin (FBL), nucleolar protein 5A (NOP56), and nucleolar protein 5 (NOP58). 28760965 5 59 theme small 970:974 arg1 complexes 1004:1012 small nucleolar ribonucleoprotein complexes 970:1012 small nucleolar ribonucleoprotein complexes (snoRNPs) 970:1022 Among the hyperstable population were three core proteins of box C/D small nucleolar ribonucleoprotein complexes (snoRNPs): fibrillarin (FBL), nucleolar protein 5A (NOP56), and nucleolar protein 5 (NOP58). 28760965 0 60 theme C/D 86:88 arg1 biogenesis 97:106 box C/D snoRNP biogenesis 82:106 box C/D snoRNP biogenesis 82:106 Quantitative time-resolved chemoproteomics reveals that stable O-GlcNAc regulates box C/D snoRNP biogenesis. 28760965 3 61 theme minimal 684:690 arg1 removal 692:698 minimal removal 684:698 minimal removal of O-GlcNAc 684:710 Applying qTOP, we quantified the turnover rates of 533 O-GlcNAcylated proteins in NIH 3T3 cells and discovered that about 14% exhibited minimal removal of O-GlcNAc or degradation of protein backbones. 28760965 3 62 theme 3T3 634:636 arg1 cells 638:642 NIH 3T3 cells 630:642 NIH 3T3 cells 630:642 Applying qTOP, we quantified the turnover rates of 533 O-GlcNAcylated proteins in NIH 3T3 cells and discovered that about 14% exhibited minimal removal of O-GlcNAc or degradation of protein backbones. 28760965 1 63 theme ubiquitous 153:162 arg1 GlcNAcylation 118:130 O-linked GlcNAcylation 109:130 O-linked GlcNAcylation (O-GlcNAcylation) 109:148 O-linked GlcNAcylation (O-GlcNAcylation), a ubiquitous posttranslational modification on intracellular proteins, is dynamically regulated in cells. 28760965 1 63 theme ubiquitous 153:162 arg1 modification 182:193 a ubiquitous posttranslational modification 151:193 a ubiquitous posttranslational modification on intracellular proteins 151:219 O-linked GlcNAcylation (O-GlcNAcylation), a ubiquitous posttranslational modification on intracellular proteins, is dynamically regulated in cells. 28760965 3 64 from rates 590:594 arg1 cells 638:642 NIH 3T3 cells 630:642 NIH 3T3 cells 630:642 Applying qTOP, we quantified the turnover rates of 533 O-GlcNAcylated proteins in NIH 3T3 cells and discovered that about 14% exhibited minimal removal of O-GlcNAc or degradation of protein backbones. 28760965 1 65 link O-linked 109:116 arg1 modification 182:193 a ubiquitous posttranslational modification 151:193 a ubiquitous posttranslational modification on intracellular proteins 151:219 O-linked GlcNAcylation (O-GlcNAcylation), a ubiquitous posttranslational modification on intracellular proteins, is dynamically regulated in cells. 28760965 1 65 link O-linked 109:116 arg1 O-GlcNAcylation 133:147 O-GlcNAcylation 133:147 O-GlcNAcylation 133:147 O-linked GlcNAcylation (O-GlcNAcylation), a ubiquitous posttranslational modification on intracellular proteins, is dynamically regulated in cells. 28760965 1 65 link O-linked 109:116 arg1 GlcNAcylation 118:130 O-linked GlcNAcylation 109:130 O-linked GlcNAcylation (O-GlcNAcylation) 109:148 O-linked GlcNAcylation (O-GlcNAcylation), a ubiquitous posttranslational modification on intracellular proteins, is dynamically regulated in cells. 28760965 0 66 theme box 82:84 arg1 biogenesis 97:106 box C/D snoRNP biogenesis 82:106 box C/D snoRNP biogenesis 82:106 Quantitative time-resolved chemoproteomics reveals that stable O-GlcNAc regulates box C/D snoRNP biogenesis. 28760965 2 67 theme turnover 272:279 arg1 dynamics 281:288 the turnover dynamics 268:288 the turnover dynamics of O-GlcNAcylated proteins 268:315 To analyze the turnover dynamics of O-GlcNAcylated proteins, we developed a quantitative time-resolved O-linked GlcNAc proteomics (qTOP) strategy based on metabolic pulse-chase labeling with an O-GlcNAc chemical reporter and stable isotope labeling with amino acids in cell culture (SILAC). 28760965 7 68 theme cell 1293:1296 arg1 proliferation 1298:1310 cancer cell proliferation 1286:1310 cancer cell proliferation 1286:1310 Blocking O-GlcNAcylation on FBL altered the 2'-O-methylation of rRNAs and impaired cancer cell proliferation and tumor formation in vivo. 28760965 1 69 theme posttranslational 164:180 arg1 GlcNAcylation 118:130 O-linked GlcNAcylation 109:130 O-linked GlcNAcylation (O-GlcNAcylation) 109:148 O-linked GlcNAcylation (O-GlcNAcylation), a ubiquitous posttranslational modification on intracellular proteins, is dynamically regulated in cells. 28760965 1 69 theme posttranslational 164:180 arg1 modification 182:193 a ubiquitous posttranslational modification 151:193 a ubiquitous posttranslational modification on intracellular proteins 151:219 O-linked GlcNAcylation (O-GlcNAcylation), a ubiquitous posttranslational modification on intracellular proteins, is dynamically regulated in cells. 27878326 8 0 theme TNF-α 1228:1232 arg1 expression 1252:1261 IL-6, TNF-α, IL-1β, and IL-12 expression 1222:1261 IL-6, TNF-α, IL-1β, and IL-12 expression 1222:1261 Co-immunoprecipitation and OGN siRNA experiments revealed that this 72-kDa variant activates the toll-like receptor-4 (TLR4) with a concomitant increase in IL-6, TNF-α, IL-1β, and IL-12 expression. 27878326 11 1 theme glycosylation 1587:1599 arg1 sulfate-OGN 1506:1516 the 34-kDa dermatan sulfate-OGN 1486:1516 the 34-kDa dermatan sulfate-OGN 1486:1516 In contrast, the 34-kDa dermatan sulfate-OGN, involved in collagen cross linking, was also the result of O-linked glycosylation. 27878326 11 1 theme glycosylation 1587:1599 arg1 result 1568:1573 the result 1564:1573 the result of O-linked glycosylation 1564:1599 In contrast, the 34-kDa dermatan sulfate-OGN, involved in collagen cross linking, was also the result of O-linked glycosylation. 27878326 11 2 link O-linked 1578:1585 arg1 glycosylation 1587:1599 O-linked glycosylation 1578:1599 O-linked glycosylation 1578:1599 In contrast, the 34-kDa dermatan sulfate-OGN, involved in collagen cross linking, was also the result of O-linked glycosylation. 27878326 8 3 theme IL-1β 1235:1239 arg1 expression 1252:1261 IL-6, TNF-α, IL-1β, and IL-12 expression 1222:1261 IL-6, TNF-α, IL-1β, and IL-12 expression 1222:1261 Co-immunoprecipitation and OGN siRNA experiments revealed that this 72-kDa variant activates the toll-like receptor-4 (TLR4) with a concomitant increase in IL-6, TNF-α, IL-1β, and IL-12 expression. 27878326 4 4 theme OGN 606:608 arg1 predominant 618:628 predominant 618:628 predominant 618:628 METHODS AND RESULTS This study uncovered a previously unidentified 72-kDa variant of OGN that is predominant in cardiac human and mouse samples of viral myocarditis. 27878326 4 4 theme OGN 606:608 arg1 variant 595:601 a previously unidentified 72-kDa variant 562:601 a previously unidentified 72-kDa variant of OGN that is predominant in cardiac human and mouse samples of viral myocarditis 562:684 METHODS AND RESULTS This study uncovered a previously unidentified 72-kDa variant of OGN that is predominant in cardiac human and mouse samples of viral myocarditis. 27878326 10 5 link O-linked 1415:1422 arg1 glycosylation 1424:1436 O-linked glycosylation 1415:1436 O-linked glycosylation of the 32-kDa protein core of OGN 1415:1470 Finally, the 72-kDa chondroitin sulfate is the result of O-linked glycosylation of the 32-kDa protein core of OGN. 27878326 6 6 theme endotoxemia 861:871 arg1 going 873:877 lipopolysaccharide-induced endotoxemia going 834:877 lipopolysaccharide-induced endotoxemia going 834:877 It also delayed mortality in lipopolysaccharide-induced endotoxemia going along with a reduced systemic production of pro-inflammatory cytokines. 27878326 9 7 theme immune 1269:1274 arg1 activation 1281:1290 This immune cell activation 1264:1290 This immune cell activation by OGN 1264:1297 This immune cell activation by OGN occurred via MyD88 and increased phosphorylation of c-jun. 27878326 4 8 theme myocarditis 674:684 arg1 samples 657:663 cardiac human and mouse samples 633:663 cardiac human and mouse samples of viral myocarditis 633:684 METHODS AND RESULTS This study uncovered a previously unidentified 72-kDa variant of OGN that is predominant in cardiac human and mouse samples of viral myocarditis. 27878326 2 9 theme proteoglycan 327:338 arg1 family 347:352 the small leucine-rich repeat proteoglycan (SLRP) family 297:352 the small leucine-rich repeat proteoglycan (SLRP) family 297:352 Osteoglycin (OGN) is part of the small leucine-rich repeat proteoglycan (SLRP) family. 27878326 14 10 from injury 1930:1935 arg1 myocarditis 1946:1956 viral myocarditis 1940:1956 viral myocarditis 1940:1956 The absence of OGN decreases cytokine production by both circulating and cardiac leukocytes upon (systemic) LPS exposure, and reduces cardiac inflammation and injury in viral myocarditis. 27878326 12 11 theme chondroitin 1657:1667 arg1 sulfate-OGN 1669:1679 a novel 72-kDa chondroitin sulfate-OGN 1642:1679 a novel 72-kDa chondroitin sulfate-OGN that is specific for innate immune cells 1642:1720 CONCLUSION The current study discovered a novel 72-kDa chondroitin sulfate-OGN that is specific for innate immune cells. 27878326 12 11 theme chondroitin 1657:1667 arg1 specific 1689:1696 specific 1689:1696 specific 1689:1696 CONCLUSION The current study discovered a novel 72-kDa chondroitin sulfate-OGN that is specific for innate immune cells. 27878326 8 12 theme siRNA 1097:1101 arg1 experiments 1103:1113 Co-immunoprecipitation and OGN siRNA experiments 1066:1113 experiments 1103:1113 Co-immunoprecipitation and OGN siRNA experiments revealed that this 72-kDa variant activates the toll-like receptor-4 (TLR4) with a concomitant increase in IL-6, TNF-α, IL-1β, and IL-12 expression. 27878326 4 13 theme human 641:645 arg1 samples 657:663 cardiac human and mouse samples 633:663 cardiac human and mouse samples of viral myocarditis 633:684 METHODS AND RESULTS This study uncovered a previously unidentified 72-kDa variant of OGN that is predominant in cardiac human and mouse samples of viral myocarditis. 27878326 5 14 from injury 756:761 arg1 myocarditis 792:802 Coxsackievirus-B3-induced myocarditis 766:802 Coxsackievirus-B3-induced myocarditis 766:802 Its absence in mice significantly decreased cardiac inflammation and injury in Coxsackievirus-B3-induced myocarditis. 27878326 2 15 theme leucine-rich 307:318 arg1 family 347:352 the small leucine-rich repeat proteoglycan (SLRP) family 297:352 the small leucine-rich repeat proteoglycan (SLRP) family 297:352 Osteoglycin (OGN) is part of the small leucine-rich repeat proteoglycan (SLRP) family. 27878326 1 16 theme excessive 228:236 arg1 infiltration 238:249 excessive infiltration 228:249 excessive infiltration of immune cells 228:265 BACKGROUND Viral myocarditis can severely damage the myocardium through excessive infiltration of immune cells. 27878326 4 17 theme mouse 651:655 arg1 samples 657:663 cardiac human and mouse samples 633:663 cardiac human and mouse samples of viral myocarditis 633:684 METHODS AND RESULTS This study uncovered a previously unidentified 72-kDa variant of OGN that is predominant in cardiac human and mouse samples of viral myocarditis. 27878326 5 18 theme cardiac 731:737 arg1 inflammation 739:750 inflammation 739:750 inflammation 739:750 Its absence in mice significantly decreased cardiac inflammation and injury in Coxsackievirus-B3-induced myocarditis. 27878326 5 19 from inflammation 739:750 arg1 myocarditis 792:802 Coxsackievirus-B3-induced myocarditis 766:802 Coxsackievirus-B3-induced myocarditis 766:802 Its absence in mice significantly decreased cardiac inflammation and injury in Coxsackievirus-B3-induced myocarditis. 27878326 14 20 theme cardiac 1905:1911 arg1 inflammation 1913:1924 cardiac inflammation 1905:1924 cardiac inflammation 1905:1924 The absence of OGN decreases cytokine production by both circulating and cardiac leukocytes upon (systemic) LPS exposure, and reduces cardiac inflammation and injury in viral myocarditis. 27878326 12 21 theme novel 1644:1648 arg1 sulfate-OGN 1669:1679 a novel 72-kDa chondroitin sulfate-OGN 1642:1679 a novel 72-kDa chondroitin sulfate-OGN that is specific for innate immune cells 1642:1720 CONCLUSION The current study discovered a novel 72-kDa chondroitin sulfate-OGN that is specific for innate immune cells. 27878326 12 21 theme novel 1644:1648 arg1 specific 1689:1696 specific 1689:1696 specific 1689:1696 CONCLUSION The current study discovered a novel 72-kDa chondroitin sulfate-OGN that is specific for innate immune cells. 27878326 4 22 from predominant 618:628 arg1 samples 657:663 cardiac human and mouse samples 633:663 cardiac human and mouse samples of viral myocarditis 633:684 METHODS AND RESULTS This study uncovered a previously unidentified 72-kDa variant of OGN that is predominant in cardiac human and mouse samples of viral myocarditis. 27878326 9 23 theme c-jun 1351:1355 arg1 phosphorylation 1332:1346 phosphorylation 1332:1346 phosphorylation of c-jun 1332:1355 This immune cell activation by OGN occurred via MyD88 and increased phosphorylation of c-jun. 27878326 1 24 theme Viral 167:171 arg1 myocarditis 173:183 BACKGROUND Viral myocarditis 156:183 BACKGROUND Viral myocarditis 156:183 BACKGROUND Viral myocarditis can severely damage the myocardium through excessive infiltration of immune cells. 27878326 12 25 theme current 1617:1623 arg1 study 1625:1629 The current study 1613:1629 The current study 1613:1629 CONCLUSION The current study discovered a novel 72-kDa chondroitin sulfate-OGN that is specific for innate immune cells. 27878326 0 26 theme receptor 82:89 arg1 activation 58:67 the activation 54:67 the activation of toll-like receptor 4 54:91 A novel 72-kDa leukocyte-derived osteoglycin enhances the activation of toll-like receptor 4 and exacerbates cardiac inflammation during viral myocarditis. 27878326 7 27 theme cardiac 1029:1035 arg1 macrophages 1037:1047 circulating and resident cardiac macrophages 1004:1047 circulating and resident cardiac macrophages 1004:1047 This 72-kDa OGN is expressed in the cell membrane of circulating and resident cardiac macrophages and neutrophils. 27878326 10 28 theme protein 1452:1458 arg1 core 1460:1463 the 32-kDa protein core 1441:1463 the 32-kDa protein core of OGN 1441:1470 Finally, the 72-kDa chondroitin sulfate is the result of O-linked glycosylation of the 32-kDa protein core of OGN. 27878326 11 29 theme dermatan 1497:1504 arg1 sulfate-OGN 1506:1516 the 34-kDa dermatan sulfate-OGN 1486:1516 the 34-kDa dermatan sulfate-OGN 1486:1516 In contrast, the 34-kDa dermatan sulfate-OGN, involved in collagen cross linking, was also the result of O-linked glycosylation. 27878326 11 29 theme dermatan 1497:1504 arg1 result 1568:1573 the result 1564:1573 the result of O-linked glycosylation 1564:1599 In contrast, the 34-kDa dermatan sulfate-OGN, involved in collagen cross linking, was also the result of O-linked glycosylation. 27878326 0 30 theme cardiac 109:115 arg1 inflammation 117:128 cardiac inflammation 109:128 cardiac inflammation 109:128 A novel 72-kDa leukocyte-derived osteoglycin enhances the activation of toll-like receptor 4 and exacerbates cardiac inflammation during viral myocarditis. 27878326 11 31 from result 1568:1573 arg1 contrast 1476:1483 contrast 1476:1483 contrast 1476:1483 In contrast, the 34-kDa dermatan sulfate-OGN, involved in collagen cross linking, was also the result of O-linked glycosylation. 27878326 3 32 theme fibrotic 390:397 arg1 processes 399:407 inflammatory and fibrotic processes 373:407 inflammatory and fibrotic processes 373:407 SLRP's may affect inflammatory and fibrotic processes, but the implication of OGN in cardiac inflammation and the resulting injury upon viral myocarditis is unknown. 27878326 0 33 theme toll-like 72:80 arg1 receptor 82:89 toll-like receptor 4 72:91 toll-like receptor 4 72:91 A novel 72-kDa leukocyte-derived osteoglycin enhances the activation of toll-like receptor 4 and exacerbates cardiac inflammation during viral myocarditis. 27878326 14 34 theme systemic 1869:1876 arg1 exposure 1883:1890 (systemic) LPS exposure 1868:1890 (systemic) LPS exposure 1868:1890 The absence of OGN decreases cytokine production by both circulating and cardiac leukocytes upon (systemic) LPS exposure, and reduces cardiac inflammation and injury in viral myocarditis. 27878326 7 35 theme cell 987:990 arg1 membrane 992:999 the cell membrane 983:999 the cell membrane of circulating and resident cardiac macrophages and neutrophils 983:1063 This 72-kDa OGN is expressed in the cell membrane of circulating and resident cardiac macrophages and neutrophils. 27878326 3 36 theme inflammatory 373:384 arg1 processes 399:407 inflammatory and fibrotic processes 373:407 inflammatory and fibrotic processes 373:407 SLRP's may affect inflammatory and fibrotic processes, but the implication of OGN in cardiac inflammation and the resulting injury upon viral myocarditis is unknown. 27878326 10 37 theme 32-kDa 1445:1450 arg1 core 1460:1463 the 32-kDa protein core 1441:1463 the 32-kDa protein core of OGN 1441:1470 Finally, the 72-kDa chondroitin sulfate is the result of O-linked glycosylation of the 32-kDa protein core of OGN. 27878326 10 38 theme chondroitin 1378:1388 arg1 result 1405:1410 the result 1401:1410 the result of O-linked glycosylation of the 32-kDa protein core of OGN 1401:1470 Finally, the 72-kDa chondroitin sulfate is the result of O-linked glycosylation of the 32-kDa protein core of OGN. 27878326 10 38 theme chondroitin 1378:1388 arg1 sulfate 1390:1396 the 72-kDa chondroitin sulfate 1367:1396 the 72-kDa chondroitin sulfate 1367:1396 Finally, the 72-kDa chondroitin sulfate is the result of O-linked glycosylation of the 32-kDa protein core of OGN. 27878326 0 39 theme 72-kDa 8:13 arg1 osteoglycin 33:43 A novel 72-kDa leukocyte-derived osteoglycin 0:43 A novel 72-kDa leukocyte-derived osteoglycin 0:43 A novel 72-kDa leukocyte-derived osteoglycin enhances the activation of toll-like receptor 4 and exacerbates cardiac inflammation during viral myocarditis. 27878326 6 40 theme cytokines 940:948 arg1 production 909:918 a reduced systemic production 890:918 a reduced systemic production of pro-inflammatory cytokines 890:948 It also delayed mortality in lipopolysaccharide-induced endotoxemia going along with a reduced systemic production of pro-inflammatory cytokines. 27878326 12 41 theme immune 1709:1714 arg1 cells 1716:1720 innate immune cells 1702:1720 innate immune cells 1702:1720 CONCLUSION The current study discovered a novel 72-kDa chondroitin sulfate-OGN that is specific for innate immune cells. 27878326 4 42 dep METHODS 521:527 arg1 uncovered 552:560 uncovered 552:560 uncovered a previously unidentified 72-kDa variant of OGN that is predominant in cardiac human and mouse samples of viral myocarditis 552:684 METHODS AND RESULTS This study uncovered a previously unidentified 72-kDa variant of OGN that is predominant in cardiac human and mouse samples of viral myocarditis. 27878326 6 43 from mortality 821:829 arg1 going 873:877 lipopolysaccharide-induced endotoxemia going 834:877 lipopolysaccharide-induced endotoxemia going 834:877 It also delayed mortality in lipopolysaccharide-induced endotoxemia going along with a reduced systemic production of pro-inflammatory cytokines. 27878326 14 44 theme cardiac 1844:1850 arg1 leukocytes 1852:1861 both circulating and cardiac leukocytes 1823:1861 both circulating and cardiac leukocytes 1823:1861 The absence of OGN decreases cytokine production by both circulating and cardiac leukocytes upon (systemic) LPS exposure, and reduces cardiac inflammation and injury in viral myocarditis. 27878326 3 45 theme viral 491:495 arg1 myocarditis 497:507 viral myocarditis 491:507 viral myocarditis 491:507 SLRP's may affect inflammatory and fibrotic processes, but the implication of OGN in cardiac inflammation and the resulting injury upon viral myocarditis is unknown. 27878326 14 46 theme circulating 1828:1838 arg1 leukocytes 1852:1861 both circulating and cardiac leukocytes 1823:1861 both circulating and cardiac leukocytes 1823:1861 The absence of OGN decreases cytokine production by both circulating and cardiac leukocytes upon (systemic) LPS exposure, and reduces cardiac inflammation and injury in viral myocarditis. 27878326 6 47 theme systemic 900:907 arg1 production 909:918 a reduced systemic production 890:918 a reduced systemic production of pro-inflammatory cytokines 890:948 It also delayed mortality in lipopolysaccharide-induced endotoxemia going along with a reduced systemic production of pro-inflammatory cytokines. 27878326 5 48 from absence 691:697 arg1 mice 702:705 mice 702:705 mice 702:705 Its absence in mice significantly decreased cardiac inflammation and injury in Coxsackievirus-B3-induced myocarditis. 27878326 8 49 theme concomitant 1198:1208 arg1 increase 1210:1217 a concomitant increase 1196:1217 a concomitant increase in IL-6, TNF-α, IL-1β, and IL-12 expression 1196:1261 Co-immunoprecipitation and OGN siRNA experiments revealed that this 72-kDa variant activates the toll-like receptor-4 (TLR4) with a concomitant increase in IL-6, TNF-α, IL-1β, and IL-12 expression. 27878326 12 50 dep CONCLUSION 1602:1611 arg1 discovered 1631:1640 discovered 1631:1640 discovered a novel 72-kDa chondroitin sulfate-OGN that is specific for innate immune cells 1631:1720 CONCLUSION The current study discovered a novel 72-kDa chondroitin sulfate-OGN that is specific for innate immune cells. 27878326 14 51 theme cytokine 1800:1807 arg1 production 1809:1818 cytokine production 1800:1818 cytokine production by both circulating and cardiac leukocytes 1800:1861 The absence of OGN decreases cytokine production by both circulating and cardiac leukocytes upon (systemic) LPS exposure, and reduces cardiac inflammation and injury in viral myocarditis. 27878326 10 52 theme O-linked 1415:1422 arg1 glycosylation 1424:1436 O-linked glycosylation 1415:1436 O-linked glycosylation of the 32-kDa protein core of OGN 1415:1470 Finally, the 72-kDa chondroitin sulfate is the result of O-linked glycosylation of the 32-kDa protein core of OGN. 27878326 14 53 theme OGN 1786:1788 arg1 absence 1775:1781 The absence 1771:1781 The absence of OGN 1771:1788 The absence of OGN decreases cytokine production by both circulating and cardiac leukocytes upon (systemic) LPS exposure, and reduces cardiac inflammation and injury in viral myocarditis. 27878326 0 54 link leukocyte-derived 15:31 arg1 osteoglycin 33:43 A novel 72-kDa leukocyte-derived osteoglycin 0:43 A novel 72-kDa leukocyte-derived osteoglycin 0:43 A novel 72-kDa leukocyte-derived osteoglycin enhances the activation of toll-like receptor 4 and exacerbates cardiac inflammation during viral myocarditis. 27878326 4 55 theme 72-kDa 588:593 arg1 predominant 618:628 predominant 618:628 predominant 618:628 METHODS AND RESULTS This study uncovered a previously unidentified 72-kDa variant of OGN that is predominant in cardiac human and mouse samples of viral myocarditis. 27878326 4 55 theme 72-kDa 588:593 arg1 variant 595:601 a previously unidentified 72-kDa variant 562:601 a previously unidentified 72-kDa variant of OGN that is predominant in cardiac human and mouse samples of viral myocarditis 562:684 METHODS AND RESULTS This study uncovered a previously unidentified 72-kDa variant of OGN that is predominant in cardiac human and mouse samples of viral myocarditis. 27878326 10 56 theme core 1460:1463 arg1 glycosylation 1424:1436 O-linked glycosylation 1415:1436 O-linked glycosylation of the 32-kDa protein core of OGN 1415:1470 Finally, the 72-kDa chondroitin sulfate is the result of O-linked glycosylation of the 32-kDa protein core of OGN. 27878326 2 57 theme small 301:305 arg1 family 347:352 the small leucine-rich repeat proteoglycan (SLRP) family 297:352 the small leucine-rich repeat proteoglycan (SLRP) family 297:352 Osteoglycin (OGN) is part of the small leucine-rich repeat proteoglycan (SLRP) family. 27878326 8 58 theme Co-immunoprecipitation 1066:1087 arg1 experiments 1103:1113 Co-immunoprecipitation and OGN siRNA experiments 1066:1113 experiments 1103:1113 Co-immunoprecipitation and OGN siRNA experiments revealed that this 72-kDa variant activates the toll-like receptor-4 (TLR4) with a concomitant increase in IL-6, TNF-α, IL-1β, and IL-12 expression. 27878326 6 59 theme lipopolysaccharide-induced 834:859 arg1 going 873:877 lipopolysaccharide-induced endotoxemia going 834:877 lipopolysaccharide-induced endotoxemia going 834:877 It also delayed mortality in lipopolysaccharide-induced endotoxemia going along with a reduced systemic production of pro-inflammatory cytokines. 27878326 8 60 theme OGN 1093:1095 arg1 experiments 1103:1113 Co-immunoprecipitation and OGN siRNA experiments 1066:1113 experiments 1103:1113 Co-immunoprecipitation and OGN siRNA experiments revealed that this 72-kDa variant activates the toll-like receptor-4 (TLR4) with a concomitant increase in IL-6, TNF-α, IL-1β, and IL-12 expression. 27878326 9 61 theme cell 1276:1279 arg1 activation 1281:1290 This immune cell activation 1264:1290 This immune cell activation by OGN 1264:1297 This immune cell activation by OGN occurred via MyD88 and increased phosphorylation of c-jun. 27878326 4 62 from samples 657:663 arg1 predominant 618:628 predominant 618:628 predominant 618:628 METHODS AND RESULTS This study uncovered a previously unidentified 72-kDa variant of OGN that is predominant in cardiac human and mouse samples of viral myocarditis. 27878326 4 62 from samples 657:663 arg1 variant 595:601 a previously unidentified 72-kDa variant 562:601 a previously unidentified 72-kDa variant of OGN that is predominant in cardiac human and mouse samples of viral myocarditis 562:684 METHODS AND RESULTS This study uncovered a previously unidentified 72-kDa variant of OGN that is predominant in cardiac human and mouse samples of viral myocarditis. 27878326 8 63 theme IL-12 1246:1250 arg1 expression 1252:1261 IL-6, TNF-α, IL-1β, and IL-12 expression 1222:1261 IL-6, TNF-α, IL-1β, and IL-12 expression 1222:1261 Co-immunoprecipitation and OGN siRNA experiments revealed that this 72-kDa variant activates the toll-like receptor-4 (TLR4) with a concomitant increase in IL-6, TNF-α, IL-1β, and IL-12 expression. 27878326 4 64 theme viral 668:672 arg1 myocarditis 674:684 viral myocarditis 668:684 viral myocarditis 668:684 METHODS AND RESULTS This study uncovered a previously unidentified 72-kDa variant of OGN that is predominant in cardiac human and mouse samples of viral myocarditis. 27878326 0 65 theme viral 137:141 arg1 myocarditis 143:153 viral myocarditis 137:153 viral myocarditis 137:153 A novel 72-kDa leukocyte-derived osteoglycin enhances the activation of toll-like receptor 4 and exacerbates cardiac inflammation during viral myocarditis. 27878326 10 66 theme OGN 1468:1470 arg1 core 1460:1463 the 32-kDa protein core 1441:1463 the 32-kDa protein core of OGN 1441:1470 Finally, the 72-kDa chondroitin sulfate is the result of O-linked glycosylation of the 32-kDa protein core of OGN. 27878326 2 67 theme repeat 320:325 arg1 family 347:352 the small leucine-rich repeat proteoglycan (SLRP) family 297:352 the small leucine-rich repeat proteoglycan (SLRP) family 297:352 Osteoglycin (OGN) is part of the small leucine-rich repeat proteoglycan (SLRP) family. 27878326 14 68 theme viral 1940:1944 arg1 myocarditis 1946:1956 viral myocarditis 1940:1956 viral myocarditis 1940:1956 The absence of OGN decreases cytokine production by both circulating and cardiac leukocytes upon (systemic) LPS exposure, and reduces cardiac inflammation and injury in viral myocarditis. 27878326 4 69 theme cardiac 633:639 arg1 samples 657:663 cardiac human and mouse samples 633:663 cardiac human and mouse samples of viral myocarditis 633:684 METHODS AND RESULTS This study uncovered a previously unidentified 72-kDa variant of OGN that is predominant in cardiac human and mouse samples of viral myocarditis. 27878326 4 70 attach predominant 618:628 arg2 predominant 618:628 predominant 618:628 predominant 618:628 METHODS AND RESULTS This study uncovered a previously unidentified 72-kDa variant of OGN that is predominant in cardiac human and mouse samples of viral myocarditis. 27878326 4 70 attach predominant 618:628 arg1 samples 657:663 cardiac human and mouse samples 633:663 cardiac human and mouse samples of viral myocarditis 633:684 METHODS AND RESULTS This study uncovered a previously unidentified 72-kDa variant of OGN that is predominant in cardiac human and mouse samples of viral myocarditis. 27878326 4 70 attach predominant 618:628 arg2 variant 595:601 a previously unidentified 72-kDa variant 562:601 a previously unidentified 72-kDa variant of OGN that is predominant in cardiac human and mouse samples of viral myocarditis 562:684 METHODS AND RESULTS This study uncovered a previously unidentified 72-kDa variant of OGN that is predominant in cardiac human and mouse samples of viral myocarditis. 27878326 12 71 theme 72-kDa 1650:1655 arg1 sulfate-OGN 1669:1679 a novel 72-kDa chondroitin sulfate-OGN 1642:1679 a novel 72-kDa chondroitin sulfate-OGN that is specific for innate immune cells 1642:1720 CONCLUSION The current study discovered a novel 72-kDa chondroitin sulfate-OGN that is specific for innate immune cells. 27878326 12 71 theme 72-kDa 1650:1655 arg1 specific 1689:1696 specific 1689:1696 specific 1689:1696 CONCLUSION The current study discovered a novel 72-kDa chondroitin sulfate-OGN that is specific for innate immune cells. 27878326 11 72 theme linking 1546:1552 arg1 cross 1540:1544 collagen cross linking 1531:1552 collagen cross linking 1531:1552 In contrast, the 34-kDa dermatan sulfate-OGN, involved in collagen cross linking, was also the result of O-linked glycosylation. 27878326 11 73 theme collagen 1531:1538 arg1 cross 1540:1544 collagen cross linking 1531:1552 collagen cross linking 1531:1552 In contrast, the 34-kDa dermatan sulfate-OGN, involved in collagen cross linking, was also the result of O-linked glycosylation. 27878326 5 74 theme Coxsackievirus-B3-induced 766:790 arg1 myocarditis 792:802 Coxsackievirus-B3-induced myocarditis 766:802 Coxsackievirus-B3-induced myocarditis 766:802 Its absence in mice significantly decreased cardiac inflammation and injury in Coxsackievirus-B3-induced myocarditis. 27878326 1 75 theme BACKGROUND 156:165 arg1 myocarditis 173:183 BACKGROUND Viral myocarditis 156:183 BACKGROUND Viral myocarditis 156:183 BACKGROUND Viral myocarditis can severely damage the myocardium through excessive infiltration of immune cells. 27878326 1 76 theme immune 254:259 arg1 cells 261:265 immune cells 254:265 immune cells 254:265 BACKGROUND Viral myocarditis can severely damage the myocardium through excessive infiltration of immune cells. 27878326 11 77 theme O-linked 1578:1585 arg1 glycosylation 1587:1599 O-linked glycosylation 1578:1599 O-linked glycosylation 1578:1599 In contrast, the 34-kDa dermatan sulfate-OGN, involved in collagen cross linking, was also the result of O-linked glycosylation. 27878326 7 78 theme neutrophils 1053:1063 arg1 membrane 992:999 the cell membrane 983:999 the cell membrane of circulating and resident cardiac macrophages and neutrophils 983:1063 This 72-kDa OGN is expressed in the cell membrane of circulating and resident cardiac macrophages and neutrophils. 27878326 14 79 theme LPS 1879:1881 arg1 exposure 1883:1890 (systemic) LPS exposure 1868:1890 (systemic) LPS exposure 1868:1890 The absence of OGN decreases cytokine production by both circulating and cardiac leukocytes upon (systemic) LPS exposure, and reduces cardiac inflammation and injury in viral myocarditis. 27878326 8 80 from increase 1210:1217 arg1 expression 1252:1261 IL-6, TNF-α, IL-1β, and IL-12 expression 1222:1261 IL-6, TNF-α, IL-1β, and IL-12 expression 1222:1261 Co-immunoprecipitation and OGN siRNA experiments revealed that this 72-kDa variant activates the toll-like receptor-4 (TLR4) with a concomitant increase in IL-6, TNF-α, IL-1β, and IL-12 expression. 27878326 10 81 gly glycosylation 1424:1436 arg1 core 1460:1463 the 32-kDa protein core 1441:1463 the 32-kDa protein core of OGN 1441:1470 Finally, the 72-kDa chondroitin sulfate is the result of O-linked glycosylation of the 32-kDa protein core of OGN. 27878326 3 82 from implication 418:428 arg1 injury 479:484 the resulting injury 465:484 the resulting injury upon viral myocarditis 465:507 SLRP's may affect inflammatory and fibrotic processes, but the implication of OGN in cardiac inflammation and the resulting injury upon viral myocarditis is unknown. 27878326 3 82 from implication 418:428 arg1 inflammation 448:459 cardiac inflammation 440:459 cardiac inflammation 440:459 SLRP's may affect inflammatory and fibrotic processes, but the implication of OGN in cardiac inflammation and the resulting injury upon viral myocarditis is unknown. 27878326 8 83 theme 72-kDa 1134:1139 arg1 variant 1141:1147 this 72-kDa variant 1129:1147 this 72-kDa variant 1129:1147 Co-immunoprecipitation and OGN siRNA experiments revealed that this 72-kDa variant activates the toll-like receptor-4 (TLR4) with a concomitant increase in IL-6, TNF-α, IL-1β, and IL-12 expression. 27878326 7 84 theme macrophages 1037:1047 arg1 membrane 992:999 the cell membrane 983:999 the cell membrane of circulating and resident cardiac macrophages and neutrophils 983:1063 This 72-kDa OGN is expressed in the cell membrane of circulating and resident cardiac macrophages and neutrophils. 27878326 11 85 theme 34-kDa 1490:1495 arg1 sulfate-OGN 1506:1516 the 34-kDa dermatan sulfate-OGN 1486:1516 the 34-kDa dermatan sulfate-OGN 1486:1516 In contrast, the 34-kDa dermatan sulfate-OGN, involved in collagen cross linking, was also the result of O-linked glycosylation. 27878326 11 85 theme 34-kDa 1490:1495 arg1 result 1568:1573 the result 1564:1573 the result of O-linked glycosylation 1564:1599 In contrast, the 34-kDa dermatan sulfate-OGN, involved in collagen cross linking, was also the result of O-linked glycosylation. 27878326 7 86 theme resident 1020:1027 arg1 macrophages 1037:1047 circulating and resident cardiac macrophages 1004:1047 circulating and resident cardiac macrophages 1004:1047 This 72-kDa OGN is expressed in the cell membrane of circulating and resident cardiac macrophages and neutrophils. 27878326 3 87 theme cardiac 440:446 arg1 inflammation 448:459 cardiac inflammation 440:459 cardiac inflammation 440:459 SLRP's may affect inflammatory and fibrotic processes, but the implication of OGN in cardiac inflammation and the resulting injury upon viral myocarditis is unknown. 27878326 0 88 theme novel 2:6 arg1 osteoglycin 33:43 A novel 72-kDa leukocyte-derived osteoglycin 0:43 A novel 72-kDa leukocyte-derived osteoglycin 0:43 A novel 72-kDa leukocyte-derived osteoglycin enhances the activation of toll-like receptor 4 and exacerbates cardiac inflammation during viral myocarditis. 27878326 8 89 theme toll-like 1163:1171 arg1 TLR4 1185:1188 TLR4 1185:1188 TLR4 1185:1188 Co-immunoprecipitation and OGN siRNA experiments revealed that this 72-kDa variant activates the toll-like receptor-4 (TLR4) with a concomitant increase in IL-6, TNF-α, IL-1β, and IL-12 expression. 27878326 8 89 theme toll-like 1163:1171 arg1 receptor-4 1173:1182 the toll-like receptor-4 1159:1182 the toll-like receptor-4 (TLR4) 1159:1189 Co-immunoprecipitation and OGN siRNA experiments revealed that this 72-kDa variant activates the toll-like receptor-4 (TLR4) with a concomitant increase in IL-6, TNF-α, IL-1β, and IL-12 expression. 27878326 7 90 theme circulating 1004:1014 arg1 macrophages 1037:1047 circulating and resident cardiac macrophages 1004:1047 circulating and resident cardiac macrophages 1004:1047 This 72-kDa OGN is expressed in the cell membrane of circulating and resident cardiac macrophages and neutrophils. 27878326 3 91 theme OGN 433:435 arg1 unknown 512:518 unknown 512:518 unknown 512:518 SLRP's may affect inflammatory and fibrotic processes, but the implication of OGN in cardiac inflammation and the resulting injury upon viral myocarditis is unknown. 27878326 3 91 theme OGN 433:435 arg1 implication 418:428 the implication 414:428 the implication of OGN in cardiac inflammation and the resulting injury upon viral myocarditis 414:507 SLRP's may affect inflammatory and fibrotic processes, but the implication of OGN in cardiac inflammation and the resulting injury upon viral myocarditis is unknown. 27878326 0 92 theme leukocyte-derived 15:31 arg1 osteoglycin 33:43 A novel 72-kDa leukocyte-derived osteoglycin 0:43 A novel 72-kDa leukocyte-derived osteoglycin 0:43 A novel 72-kDa leukocyte-derived osteoglycin enhances the activation of toll-like receptor 4 and exacerbates cardiac inflammation during viral myocarditis. 27878326 4 93 theme unidentified 575:586 arg1 predominant 618:628 predominant 618:628 predominant 618:628 METHODS AND RESULTS This study uncovered a previously unidentified 72-kDa variant of OGN that is predominant in cardiac human and mouse samples of viral myocarditis. 27878326 4 93 theme unidentified 575:586 arg1 variant 595:601 a previously unidentified 72-kDa variant 562:601 a previously unidentified 72-kDa variant of OGN that is predominant in cardiac human and mouse samples of viral myocarditis 562:684 METHODS AND RESULTS This study uncovered a previously unidentified 72-kDa variant of OGN that is predominant in cardiac human and mouse samples of viral myocarditis. 27878326 10 94 theme 72-kDa 1371:1376 arg1 result 1405:1410 the result 1401:1410 the result of O-linked glycosylation of the 32-kDa protein core of OGN 1401:1470 Finally, the 72-kDa chondroitin sulfate is the result of O-linked glycosylation of the 32-kDa protein core of OGN. 27878326 10 94 theme 72-kDa 1371:1376 arg1 sulfate 1390:1396 the 72-kDa chondroitin sulfate 1367:1396 the 72-kDa chondroitin sulfate 1367:1396 Finally, the 72-kDa chondroitin sulfate is the result of O-linked glycosylation of the 32-kDa protein core of OGN. 27878326 3 95 theme resulting 469:477 arg1 injury 479:484 the resulting injury 465:484 the resulting injury upon viral myocarditis 465:507 SLRP's may affect inflammatory and fibrotic processes, but the implication of OGN in cardiac inflammation and the resulting injury upon viral myocarditis is unknown. 27878326 6 96 theme pro-inflammatory 923:938 arg1 cytokines 940:948 pro-inflammatory cytokines 923:948 pro-inflammatory cytokines 923:948 It also delayed mortality in lipopolysaccharide-induced endotoxemia going along with a reduced systemic production of pro-inflammatory cytokines. 27878326 12 97 theme innate 1702:1707 arg1 cells 1716:1720 innate immune cells 1702:1720 innate immune cells 1702:1720 CONCLUSION The current study discovered a novel 72-kDa chondroitin sulfate-OGN that is specific for innate immune cells. 27878326 2 98 theme family 347:352 arg1 part 289:292 part 289:292 part of the small leucine-rich repeat proteoglycan (SLRP) family 289:352 Osteoglycin (OGN) is part of the small leucine-rich repeat proteoglycan (SLRP) family. 27878326 6 99 theme reduced 892:898 arg1 production 909:918 a reduced systemic production 890:918 a reduced systemic production of pro-inflammatory cytokines 890:948 It also delayed mortality in lipopolysaccharide-induced endotoxemia going along with a reduced systemic production of pro-inflammatory cytokines. 27878326 2 100 theme SLRP 341:344 arg1 family 347:352 the small leucine-rich repeat proteoglycan (SLRP) family 297:352 the small leucine-rich repeat proteoglycan (SLRP) family 297:352 Osteoglycin (OGN) is part of the small leucine-rich repeat proteoglycan (SLRP) family. 27878326 14 101 from inflammation 1913:1924 arg1 myocarditis 1946:1956 viral myocarditis 1940:1956 viral myocarditis 1940:1956 The absence of OGN decreases cytokine production by both circulating and cardiac leukocytes upon (systemic) LPS exposure, and reduces cardiac inflammation and injury in viral myocarditis. 27878326 1 102 theme cells 261:265 arg1 infiltration 238:249 excessive infiltration 228:249 excessive infiltration of immune cells 228:265 BACKGROUND Viral myocarditis can severely damage the myocardium through excessive infiltration of immune cells. 27878326 8 103 theme IL-6 1222:1225 arg1 expression 1252:1261 IL-6, TNF-α, IL-1β, and IL-12 expression 1222:1261 IL-6, TNF-α, IL-1β, and IL-12 expression 1222:1261 Co-immunoprecipitation and OGN siRNA experiments revealed that this 72-kDa variant activates the toll-like receptor-4 (TLR4) with a concomitant increase in IL-6, TNF-α, IL-1β, and IL-12 expression. 27878326 10 104 theme glycosylation 1424:1436 arg1 result 1405:1410 the result 1401:1410 the result of O-linked glycosylation of the 32-kDa protein core of OGN 1401:1470 Finally, the 72-kDa chondroitin sulfate is the result of O-linked glycosylation of the 32-kDa protein core of OGN. 27878326 10 104 theme glycosylation 1424:1436 arg1 sulfate 1390:1396 the 72-kDa chondroitin sulfate 1367:1396 the 72-kDa chondroitin sulfate 1367:1396 Finally, the 72-kDa chondroitin sulfate is the result of O-linked glycosylation of the 32-kDa protein core of OGN. 27878326 7 105 theme 72-kDa 956:961 arg1 OGN 963:965 This 72-kDa OGN 951:965 This 72-kDa OGN 951:965 This 72-kDa OGN is expressed in the cell membrane of circulating and resident cardiac macrophages and neutrophils. 25030920 3 0 from population 478:487 arg1 addition 411:418 elevated posttranslational addition 384:418 elevated posttranslational addition of O-linked-β-N-acetylglucosamine (O-GlcNAc) on a diverse population of nuclear and cytosolic proteins, many of which regulate signaling pathways 384:564 Stemming from glycolysis, the hexosamine biosynthetic pathway leads to elevated posttranslational addition of O-linked-β-N-acetylglucosamine (O-GlcNAc) on a diverse population of nuclear and cytosolic proteins, many of which regulate signaling pathways. 25030920 4 1 theme metabolic 612:620 arg1 alterations 622:632 metabolic alterations 612:632 metabolic alterations in cancer cells 612:648 This unit outlines techniques used to detect metabolic alterations in cancer cells, regulation by signaling pathways, and cellular O-GlcNAcylation. 25030920 2 2 theme glycolytic 296:305 arg1 flux 307:310 glycolytic flux 296:310 glycolytic flux 296:310 Oncogenes and tumor suppressors alter signaling pathways that lead to alterations of glycolytic flux. 25030920 2 3 theme flux 307:310 arg1 alterations 281:291 alterations 281:291 alterations of glycolytic flux 281:310 Oncogenes and tumor suppressors alter signaling pathways that lead to alterations of glycolytic flux. 25030920 4 4 theme cancer 637:642 arg1 cells 644:648 cancer cells 637:648 cancer cells 637:648 This unit outlines techniques used to detect metabolic alterations in cancer cells, regulation by signaling pathways, and cellular O-GlcNAcylation. 25030920 3 5 theme biosynthetic 354:365 arg1 pathway 367:373 the hexosamine biosynthetic pathway 339:373 the hexosamine biosynthetic pathway 339:373 Stemming from glycolysis, the hexosamine biosynthetic pathway leads to elevated posttranslational addition of O-linked-β-N-acetylglucosamine (O-GlcNAc) on a diverse population of nuclear and cytosolic proteins, many of which regulate signaling pathways. 25030920 4 6 theme signaling 665:673 arg1 pathways 675:682 signaling pathways 665:682 signaling pathways 665:682 This unit outlines techniques used to detect metabolic alterations in cancer cells, regulation by signaling pathways, and cellular O-GlcNAcylation. 25030920 1 7 theme Cancer 69:74 arg1 cells 76:80 Cancer cells 69:80 Cancer cells 69:80 Cancer cells exhibit a unique metabolic shift to aerobic glycolysis that has been exploited diagnostically and therapeutically in the clinic. 25030920 3 8 theme diverse 470:476 arg1 population 478:487 a diverse population 468:487 a diverse population of nuclear and cytosolic proteins, many of which regulate signaling pathways 468:564 Stemming from glycolysis, the hexosamine biosynthetic pathway leads to elevated posttranslational addition of O-linked-β-N-acetylglucosamine (O-GlcNAc) on a diverse population of nuclear and cytosolic proteins, many of which regulate signaling pathways. 25030920 3 9 from addition 411:418 arg1 population 478:487 a diverse population 468:487 a diverse population of nuclear and cytosolic proteins, many of which regulate signaling pathways 468:564 Stemming from glycolysis, the hexosamine biosynthetic pathway leads to elevated posttranslational addition of O-linked-β-N-acetylglucosamine (O-GlcNAc) on a diverse population of nuclear and cytosolic proteins, many of which regulate signaling pathways. 25030920 4 10 from O-GlcNAcylation 698:712 arg1 cells 644:648 cancer cells 637:648 cancer cells 637:648 This unit outlines techniques used to detect metabolic alterations in cancer cells, regulation by signaling pathways, and cellular O-GlcNAcylation. 25030920 4 11 theme cellular 689:696 arg1 O-GlcNAcylation 698:712 cellular O-GlcNAcylation 689:712 cellular O-GlcNAcylation 689:712 This unit outlines techniques used to detect metabolic alterations in cancer cells, regulation by signaling pathways, and cellular O-GlcNAcylation. 25030920 0 12 theme Cancer 0:5 arg1 metabolism 7:16 Cancer metabolism 0:16 Cancer metabolism 0:16 Cancer metabolism: cross talk between signaling and O-GlcNAcylation. 25030920 3 13 theme elevated 384:391 arg1 addition 411:418 elevated posttranslational addition 384:418 elevated posttranslational addition of O-linked-β-N-acetylglucosamine (O-GlcNAc) on a diverse population of nuclear and cytosolic proteins, many of which regulate signaling pathways 384:564 Stemming from glycolysis, the hexosamine biosynthetic pathway leads to elevated posttranslational addition of O-linked-β-N-acetylglucosamine (O-GlcNAc) on a diverse population of nuclear and cytosolic proteins, many of which regulate signaling pathways. 25030920 1 14 theme unique 92:97 arg1 shift 109:113 a unique metabolic shift 90:113 a unique metabolic shift to aerobic glycolysis that has been exploited diagnostically and therapeutically in the clinic 90:208 Cancer cells exhibit a unique metabolic shift to aerobic glycolysis that has been exploited diagnostically and therapeutically in the clinic. 25030920 3 15 theme posttranslational 393:409 arg1 addition 411:418 elevated posttranslational addition 384:418 elevated posttranslational addition of O-linked-β-N-acetylglucosamine (O-GlcNAc) on a diverse population of nuclear and cytosolic proteins, many of which regulate signaling pathways 384:564 Stemming from glycolysis, the hexosamine biosynthetic pathway leads to elevated posttranslational addition of O-linked-β-N-acetylglucosamine (O-GlcNAc) on a diverse population of nuclear and cytosolic proteins, many of which regulate signaling pathways. 25030920 1 16 theme metabolic 99:107 arg1 shift 109:113 a unique metabolic shift 90:113 a unique metabolic shift to aerobic glycolysis that has been exploited diagnostically and therapeutically in the clinic 90:208 Cancer cells exhibit a unique metabolic shift to aerobic glycolysis that has been exploited diagnostically and therapeutically in the clinic. 25030920 3 17 theme cytosolic 504:512 arg1 proteins 514:521 nuclear and cytosolic proteins 492:521 nuclear and cytosolic proteins 492:521 Stemming from glycolysis, the hexosamine biosynthetic pathway leads to elevated posttranslational addition of O-linked-β-N-acetylglucosamine (O-GlcNAc) on a diverse population of nuclear and cytosolic proteins, many of which regulate signaling pathways. 25030920 0 18 theme cross 19:23 arg1 talk 25:28 cross talk 19:28 cross talk between signaling and O-GlcNAcylation 19:66 Cancer metabolism: cross talk between signaling and O-GlcNAcylation. 25030920 3 19 theme nuclear 492:498 arg1 proteins 514:521 nuclear and cytosolic proteins 492:521 nuclear and cytosolic proteins 492:521 Stemming from glycolysis, the hexosamine biosynthetic pathway leads to elevated posttranslational addition of O-linked-β-N-acetylglucosamine (O-GlcNAc) on a diverse population of nuclear and cytosolic proteins, many of which regulate signaling pathways. 25030920 3 20 theme O-linked-β-N-acetylglucosamine 423:452 arg1 addition 411:418 elevated posttranslational addition 384:418 elevated posttranslational addition of O-linked-β-N-acetylglucosamine (O-GlcNAc) on a diverse population of nuclear and cytosolic proteins, many of which regulate signaling pathways 384:564 Stemming from glycolysis, the hexosamine biosynthetic pathway leads to elevated posttranslational addition of O-linked-β-N-acetylglucosamine (O-GlcNAc) on a diverse population of nuclear and cytosolic proteins, many of which regulate signaling pathways. 25030920 4 21 from regulation 651:660 arg1 cells 644:648 cancer cells 637:648 cancer cells 637:648 This unit outlines techniques used to detect metabolic alterations in cancer cells, regulation by signaling pathways, and cellular O-GlcNAcylation. 25030920 2 22 theme tumor 225:229 arg1 suppressors 231:241 tumor suppressors 225:241 tumor suppressors 225:241 Oncogenes and tumor suppressors alter signaling pathways that lead to alterations of glycolytic flux. 25030920 0 23 dep talk 25:28 arg1 metabolism 7:16 Cancer metabolism 0:16 Cancer metabolism 0:16 Cancer metabolism: cross talk between signaling and O-GlcNAcylation. 25030920 1 24 theme aerobic 118:124 arg1 glycolysis 126:135 aerobic glycolysis 118:135 aerobic glycolysis 118:135 Cancer cells exhibit a unique metabolic shift to aerobic glycolysis that has been exploited diagnostically and therapeutically in the clinic. 25030920 4 25 from alterations 622:632 arg1 cells 644:648 cancer cells 637:648 cancer cells 637:648 This unit outlines techniques used to detect metabolic alterations in cancer cells, regulation by signaling pathways, and cellular O-GlcNAcylation. 25030920 3 26 theme proteins 514:521 arg1 many 524:527 many 524:527 many 524:527 Stemming from glycolysis, the hexosamine biosynthetic pathway leads to elevated posttranslational addition of O-linked-β-N-acetylglucosamine (O-GlcNAc) on a diverse population of nuclear and cytosolic proteins, many of which regulate signaling pathways. 25030920 3 26 theme proteins 514:521 arg1 proteins 514:521 nuclear and cytosolic proteins 492:521 nuclear and cytosolic proteins 492:521 Stemming from glycolysis, the hexosamine biosynthetic pathway leads to elevated posttranslational addition of O-linked-β-N-acetylglucosamine (O-GlcNAc) on a diverse population of nuclear and cytosolic proteins, many of which regulate signaling pathways. 25030920 3 26 theme proteins 514:521 arg1 population 478:487 a diverse population 468:487 a diverse population of nuclear and cytosolic proteins, many of which regulate signaling pathways 468:564 Stemming from glycolysis, the hexosamine biosynthetic pathway leads to elevated posttranslational addition of O-linked-β-N-acetylglucosamine (O-GlcNAc) on a diverse population of nuclear and cytosolic proteins, many of which regulate signaling pathways. 25030920 3 27 theme signaling 547:555 arg1 pathways 557:564 signaling pathways 547:564 signaling pathways 547:564 Stemming from glycolysis, the hexosamine biosynthetic pathway leads to elevated posttranslational addition of O-linked-β-N-acetylglucosamine (O-GlcNAc) on a diverse population of nuclear and cytosolic proteins, many of which regulate signaling pathways. 25030920 3 28 theme hexosamine 343:352 arg1 pathway 367:373 the hexosamine biosynthetic pathway 339:373 the hexosamine biosynthetic pathway 339:373 Stemming from glycolysis, the hexosamine biosynthetic pathway leads to elevated posttranslational addition of O-linked-β-N-acetylglucosamine (O-GlcNAc) on a diverse population of nuclear and cytosolic proteins, many of which regulate signaling pathways. 25030920 3 29 from O-linked-β-N-acetylglucosamine 423:452 arg1 population 478:487 a diverse population 468:487 a diverse population of nuclear and cytosolic proteins, many of which regulate signaling pathways 468:564 Stemming from glycolysis, the hexosamine biosynthetic pathway leads to elevated posttranslational addition of O-linked-β-N-acetylglucosamine (O-GlcNAc) on a diverse population of nuclear and cytosolic proteins, many of which regulate signaling pathways. 25030920 2 30 theme signaling 249:257 arg1 pathways 259:266 signaling pathways 249:266 signaling pathways that lead to alterations of glycolytic flux 249:310 Oncogenes and tumor suppressors alter signaling pathways that lead to alterations of glycolytic flux. 24794008 5 0 theme beta-eliminated 855:869 arg1 glycans 871:877 beta-eliminated glycans 855:877 beta-eliminated glycans 855:877 O-Glycosylation in Mimivirus glycoproteins was identified by permethylation and matrix-assisted laser desorption/ionization-mass spectrometry analyses of beta-eliminated glycans. 24794008 6 1 theme end 978:980 arg1 saccharide 982:991 their reducing end saccharide 963:991 their reducing end saccharide 963:991 We sequenced 26 previously undescribed O-glycans, most of which contain glucose as their reducing end saccharide. 24794008 1 2 theme various 165:171 arg1 spp 186:188 various Acanthamoeba spp 165:188 various Acanthamoeba spp 165:188 Acanthamoeba polyphaga mimivirus is a member of the giant nucleocytoplasmic large DNA viruses, infecting various Acanthamoeba spp. 24794008 5 3 theme spectrometry 830:841 arg1 analyses 843:850 permethylation and matrix-assisted laser desorption/ionization-mass spectrometry analyses 762:850 permethylation and matrix-assisted laser desorption/ionization-mass spectrometry analyses of beta-eliminated glycans 762:877 O-Glycosylation in Mimivirus glycoproteins was identified by permethylation and matrix-assisted laser desorption/ionization-mass spectrometry analyses of beta-eliminated glycans. 24794008 5 4 theme glycans 871:877 arg1 analyses 843:850 permethylation and matrix-assisted laser desorption/ionization-mass spectrometry analyses 762:850 permethylation and matrix-assisted laser desorption/ionization-mass spectrometry analyses of beta-eliminated glycans 762:877 O-Glycosylation in Mimivirus glycoproteins was identified by permethylation and matrix-assisted laser desorption/ionization-mass spectrometry analyses of beta-eliminated glycans. 24794008 0 5 from glycosylation 9:21 arg1 mimivirus 49:57 Acanthamoeba polyphaga mimivirus 26:57 Acanthamoeba polyphaga mimivirus 26:57 O-Linked glycosylation in Acanthamoeba polyphaga mimivirus. 24794008 4 6 gly glycoproteins 686:698 arg1 glycoproteins 686:698 Mimivirus surface glycoproteins 668:698 Mimivirus surface glycoproteins 668:698 To obtain a more detailed view of glycosylation in Mimivirus, we developed a periodate oxidation-based method to selectively enrich Mimivirus surface glycoproteins. 24794008 7 7 theme glycosylation 1070:1082 arg1 significance 1054:1065 the functional significance 1039:1065 the functional significance of glycosylation in Mimivirus 1039:1095 These data will facilitate future studies on the functional significance of glycosylation in Mimivirus. 24794008 1 8 theme Acanthamoeba 173:184 arg1 spp 186:188 various Acanthamoeba spp 165:188 various Acanthamoeba spp 165:188 Acanthamoeba polyphaga mimivirus is a member of the giant nucleocytoplasmic large DNA viruses, infecting various Acanthamoeba spp. 24794008 5 9 theme matrix-assisted 781:795 arg1 spectrometry 830:841 matrix-assisted laser desorption/ionization-mass spectrometry 781:841 matrix-assisted laser desorption/ionization-mass spectrometry 781:841 O-Glycosylation in Mimivirus glycoproteins was identified by permethylation and matrix-assisted laser desorption/ionization-mass spectrometry analyses of beta-eliminated glycans. 24794008 1 10 theme polyphaga 73:81 arg1 mimivirus 83:91 Acanthamoeba polyphaga mimivirus 60:91 Acanthamoeba polyphaga mimivirus 60:91 Acanthamoeba polyphaga mimivirus is a member of the giant nucleocytoplasmic large DNA viruses, infecting various Acanthamoeba spp. 24794008 1 10 theme polyphaga 73:81 arg1 member 98:103 a member 96:103 a member of the giant nucleocytoplasmic large DNA viruses, infecting various Acanthamoeba spp 96:188 Acanthamoeba polyphaga mimivirus is a member of the giant nucleocytoplasmic large DNA viruses, infecting various Acanthamoeba spp. 24794008 5 11 theme laser 797:801 arg1 spectrometry 830:841 matrix-assisted laser desorption/ionization-mass spectrometry 781:841 matrix-assisted laser desorption/ionization-mass spectrometry 781:841 O-Glycosylation in Mimivirus glycoproteins was identified by permethylation and matrix-assisted laser desorption/ionization-mass spectrometry analyses of beta-eliminated glycans. 24794008 6 12 theme undescribed 907:917 arg1 O-glycans 919:927 26 previously undescribed O-glycans 893:927 26 previously undescribed O-glycans 893:927 We sequenced 26 previously undescribed O-glycans, most of which contain glucose as their reducing end saccharide. 24794008 3 13 theme glycosylation 511:523 arg1 machinery 525:533 its own glycosylation machinery 503:533 its own glycosylation machinery 503:533 Recent work on enzymes involved in carbohydrate biosynthesis and metabolism show that instead of utilizing host cell resources, Mimivirus produces its own glycosylation machinery. 24794008 5 14 theme desorption/ionization-mass 803:828 arg1 spectrometry 830:841 matrix-assisted laser desorption/ionization-mass spectrometry 781:841 matrix-assisted laser desorption/ionization-mass spectrometry 781:841 O-Glycosylation in Mimivirus glycoproteins was identified by permethylation and matrix-assisted laser desorption/ionization-mass spectrometry analyses of beta-eliminated glycans. 24794008 7 15 from studies 1028:1034 arg1 significance 1054:1065 the functional significance 1039:1065 the functional significance of glycosylation in Mimivirus 1039:1095 These data will facilitate future studies on the functional significance of glycosylation in Mimivirus. 24794008 3 16 theme Recent 356:361 arg1 work 363:366 Recent work 356:366 Recent work on enzymes involved in carbohydrate biosynthesis and metabolism 356:430 Recent work on enzymes involved in carbohydrate biosynthesis and metabolism show that instead of utilizing host cell resources, Mimivirus produces its own glycosylation machinery. 24794008 3 17 theme carbohydrate 391:402 arg1 biosynthesis 404:415 carbohydrate biosynthesis 391:415 carbohydrate biosynthesis 391:415 Recent work on enzymes involved in carbohydrate biosynthesis and metabolism show that instead of utilizing host cell resources, Mimivirus produces its own glycosylation machinery. 24794008 4 18 theme surface 678:684 arg1 glycoproteins 686:698 Mimivirus surface glycoproteins 668:698 Mimivirus surface glycoproteins 668:698 To obtain a more detailed view of glycosylation in Mimivirus, we developed a periodate oxidation-based method to selectively enrich Mimivirus surface glycoproteins. 24794008 4 19 theme glycosylation 570:582 arg1 view 562:565 a more detailed view 546:565 a more detailed view of glycosylation in Mimivirus 546:595 To obtain a more detailed view of glycosylation in Mimivirus, we developed a periodate oxidation-based method to selectively enrich Mimivirus surface glycoproteins. 24794008 2 20 dep such 291:294 arg1 as 296:297 as 296:297 as 296:297 The genomes of giant viruses encode components previously thought to be exclusive to cellular life, such as proteins involved in nucleic acid and protein synthesis. 24794008 7 21 theme functional 1043:1052 arg1 significance 1054:1065 the functional significance 1039:1065 the functional significance of glycosylation in Mimivirus 1039:1095 These data will facilitate future studies on the functional significance of glycosylation in Mimivirus. 24794008 2 22 theme nucleic 320:326 arg1 acid 328:331 nucleic acid 320:331 nucleic acid 320:331 The genomes of giant viruses encode components previously thought to be exclusive to cellular life, such as proteins involved in nucleic acid and protein synthesis. 24794008 0 23 theme O-Linked 0:7 arg1 glycosylation 9:21 O-Linked glycosylation 0:21 O-Linked glycosylation in Acanthamoeba polyphaga mimivirus 0:57 O-Linked glycosylation in Acanthamoeba polyphaga mimivirus. 24794008 0 24 theme Acanthamoeba 26:37 arg1 mimivirus 49:57 Acanthamoeba polyphaga mimivirus 26:57 Acanthamoeba polyphaga mimivirus 26:57 O-Linked glycosylation in Acanthamoeba polyphaga mimivirus. 24794008 6 25 contain contain 944:950 arg1 most 930:933 most 930:933 most 930:933 We sequenced 26 previously undescribed O-glycans, most of which contain glucose as their reducing end saccharide. 24794008 6 25 contain contain 944:950 arg1 O-glycans 919:927 26 previously undescribed O-glycans 893:927 26 previously undescribed O-glycans 893:927 We sequenced 26 previously undescribed O-glycans, most of which contain glucose as their reducing end saccharide. 24794008 6 25 contain contain 944:950 arg2 glucose 952:958 glucose 952:958 glucose 952:958 We sequenced 26 previously undescribed O-glycans, most of which contain glucose as their reducing end saccharide. 24794008 4 26 from view 562:565 arg1 Mimivirus 587:595 Mimivirus 587:595 Mimivirus 587:595 To obtain a more detailed view of glycosylation in Mimivirus, we developed a periodate oxidation-based method to selectively enrich Mimivirus surface glycoproteins. 24794008 6 27 theme reducing 969:976 arg1 saccharide 982:991 their reducing end saccharide 963:991 their reducing end saccharide 963:991 We sequenced 26 previously undescribed O-glycans, most of which contain glucose as their reducing end saccharide. 24794008 1 28 theme giant 112:116 arg1 viruses 146:152 the giant nucleocytoplasmic large DNA viruses 108:152 the giant nucleocytoplasmic large DNA viruses 108:152 Acanthamoeba polyphaga mimivirus is a member of the giant nucleocytoplasmic large DNA viruses, infecting various Acanthamoeba spp. 24794008 2 29 theme protein 337:343 arg1 synthesis 345:353 protein synthesis 337:353 protein synthesis 337:353 The genomes of giant viruses encode components previously thought to be exclusive to cellular life, such as proteins involved in nucleic acid and protein synthesis. 24794008 5 30 theme permethylation 762:775 arg1 analyses 843:850 permethylation and matrix-assisted laser desorption/ionization-mass spectrometry analyses 762:850 permethylation and matrix-assisted laser desorption/ionization-mass spectrometry analyses of beta-eliminated glycans 762:877 O-Glycosylation in Mimivirus glycoproteins was identified by permethylation and matrix-assisted laser desorption/ionization-mass spectrometry analyses of beta-eliminated glycans. 24794008 4 31 theme Mimivirus 668:676 arg1 glycoproteins 686:698 Mimivirus surface glycoproteins 668:698 Mimivirus surface glycoproteins 668:698 To obtain a more detailed view of glycosylation in Mimivirus, we developed a periodate oxidation-based method to selectively enrich Mimivirus surface glycoproteins. 24794008 3 32 theme host 463:466 arg1 resources 473:481 host cell resources 463:481 host cell resources 463:481 Recent work on enzymes involved in carbohydrate biosynthesis and metabolism show that instead of utilizing host cell resources, Mimivirus produces its own glycosylation machinery. 24794008 0 33 theme polyphaga 39:47 arg1 mimivirus 49:57 Acanthamoeba polyphaga mimivirus 26:57 Acanthamoeba polyphaga mimivirus 26:57 O-Linked glycosylation in Acanthamoeba polyphaga mimivirus. 24794008 3 34 from work 363:366 arg1 enzymes 371:377 enzymes 371:377 enzymes involved in carbohydrate biosynthesis and metabolism 371:430 Recent work on enzymes involved in carbohydrate biosynthesis and metabolism show that instead of utilizing host cell resources, Mimivirus produces its own glycosylation machinery. 24794008 0 35 gly glycosylation 9:21 arg1 mimivirus 49:57 Acanthamoeba polyphaga mimivirus 26:57 Acanthamoeba polyphaga mimivirus 26:57 O-Linked glycosylation in Acanthamoeba polyphaga mimivirus. 24794008 3 36 theme cell 468:471 arg1 resources 473:481 host cell resources 463:481 host cell resources 463:481 Recent work on enzymes involved in carbohydrate biosynthesis and metabolism show that instead of utilizing host cell resources, Mimivirus produces its own glycosylation machinery. 24794008 5 37 from O-Glycosylation 701:715 arg1 glycoproteins 730:742 Mimivirus glycoproteins 720:742 Mimivirus glycoproteins 720:742 O-Glycosylation in Mimivirus glycoproteins was identified by permethylation and matrix-assisted laser desorption/ionization-mass spectrometry analyses of beta-eliminated glycans. 24794008 1 38 theme nucleocytoplasmic 118:134 arg1 viruses 146:152 the giant nucleocytoplasmic large DNA viruses 108:152 the giant nucleocytoplasmic large DNA viruses 108:152 Acanthamoeba polyphaga mimivirus is a member of the giant nucleocytoplasmic large DNA viruses, infecting various Acanthamoeba spp. 24794008 5 39 gly glycoproteins 730:742 arg1 glycoproteins 730:742 Mimivirus glycoproteins 720:742 Mimivirus glycoproteins 720:742 O-Glycosylation in Mimivirus glycoproteins was identified by permethylation and matrix-assisted laser desorption/ionization-mass spectrometry analyses of beta-eliminated glycans. 24794008 4 40 theme detailed 553:560 arg1 view 562:565 a more detailed view 546:565 a more detailed view of glycosylation in Mimivirus 546:595 To obtain a more detailed view of glycosylation in Mimivirus, we developed a periodate oxidation-based method to selectively enrich Mimivirus surface glycoproteins. 24794008 5 41 theme Mimivirus 720:728 arg1 glycoproteins 730:742 Mimivirus glycoproteins 720:742 Mimivirus glycoproteins 720:742 O-Glycosylation in Mimivirus glycoproteins was identified by permethylation and matrix-assisted laser desorption/ionization-mass spectrometry analyses of beta-eliminated glycans. 24794008 1 42 theme large 136:140 arg1 viruses 146:152 the giant nucleocytoplasmic large DNA viruses 108:152 the giant nucleocytoplasmic large DNA viruses 108:152 Acanthamoeba polyphaga mimivirus is a member of the giant nucleocytoplasmic large DNA viruses, infecting various Acanthamoeba spp. 24794008 2 43 theme viruses 212:218 arg1 components 227:236 components 227:236 components previously thought to be exclusive to cellular life 227:288 The genomes of giant viruses encode components previously thought to be exclusive to cellular life, such as proteins involved in nucleic acid and protein synthesis. 24794008 2 43 theme viruses 212:218 arg1 genomes 195:201 The genomes 191:201 The genomes of giant viruses 191:218 The genomes of giant viruses encode components previously thought to be exclusive to cellular life, such as proteins involved in nucleic acid and protein synthesis. 24794008 2 43 theme viruses 212:218 arg1 proteins 299:306 proteins 299:306 proteins involved in nucleic acid and protein synthesis 299:353 The genomes of giant viruses encode components previously thought to be exclusive to cellular life, such as proteins involved in nucleic acid and protein synthesis. 24794008 2 44 theme cellular 276:283 arg1 life 285:288 cellular life 276:288 cellular life 276:288 The genomes of giant viruses encode components previously thought to be exclusive to cellular life, such as proteins involved in nucleic acid and protein synthesis. 24794008 1 45 theme DNA 142:144 arg1 viruses 146:152 the giant nucleocytoplasmic large DNA viruses 108:152 the giant nucleocytoplasmic large DNA viruses 108:152 Acanthamoeba polyphaga mimivirus is a member of the giant nucleocytoplasmic large DNA viruses, infecting various Acanthamoeba spp. 24794008 7 46 theme future 1021:1026 arg1 studies 1028:1034 future studies 1021:1034 future studies on the functional significance of glycosylation in Mimivirus 1021:1095 These data will facilitate future studies on the functional significance of glycosylation in Mimivirus. 24794008 4 47 theme periodate 613:621 arg1 method 639:644 a periodate oxidation-based method 611:644 a periodate oxidation-based method to selectively enrich Mimivirus surface glycoproteins 611:698 To obtain a more detailed view of glycosylation in Mimivirus, we developed a periodate oxidation-based method to selectively enrich Mimivirus surface glycoproteins. 24794008 2 48 theme giant 206:210 arg1 viruses 212:218 giant viruses 206:218 giant viruses 206:218 The genomes of giant viruses encode components previously thought to be exclusive to cellular life, such as proteins involved in nucleic acid and protein synthesis. 24794008 1 49 theme viruses 146:152 arg1 mimivirus 83:91 Acanthamoeba polyphaga mimivirus 60:91 Acanthamoeba polyphaga mimivirus 60:91 Acanthamoeba polyphaga mimivirus is a member of the giant nucleocytoplasmic large DNA viruses, infecting various Acanthamoeba spp. 24794008 1 49 theme viruses 146:152 arg1 member 98:103 a member 96:103 a member of the giant nucleocytoplasmic large DNA viruses, infecting various Acanthamoeba spp 96:188 Acanthamoeba polyphaga mimivirus is a member of the giant nucleocytoplasmic large DNA viruses, infecting various Acanthamoeba spp. 24794008 7 50 from significance 1054:1065 arg1 Mimivirus 1087:1095 Mimivirus 1087:1095 Mimivirus 1087:1095 These data will facilitate future studies on the functional significance of glycosylation in Mimivirus. 24794008 1 51 theme Acanthamoeba 60:71 arg1 mimivirus 83:91 Acanthamoeba polyphaga mimivirus 60:91 Acanthamoeba polyphaga mimivirus 60:91 Acanthamoeba polyphaga mimivirus is a member of the giant nucleocytoplasmic large DNA viruses, infecting various Acanthamoeba spp. 24794008 1 51 theme Acanthamoeba 60:71 arg1 member 98:103 a member 96:103 a member of the giant nucleocytoplasmic large DNA viruses, infecting various Acanthamoeba spp 96:188 Acanthamoeba polyphaga mimivirus is a member of the giant nucleocytoplasmic large DNA viruses, infecting various Acanthamoeba spp. 24794008 3 52 theme own 507:509 arg1 machinery 525:533 its own glycosylation machinery 503:533 its own glycosylation machinery 503:533 Recent work on enzymes involved in carbohydrate biosynthesis and metabolism show that instead of utilizing host cell resources, Mimivirus produces its own glycosylation machinery. 24794008 4 53 theme oxidation-based 623:637 arg1 method 639:644 a periodate oxidation-based method 611:644 a periodate oxidation-based method to selectively enrich Mimivirus surface glycoproteins 611:698 To obtain a more detailed view of glycosylation in Mimivirus, we developed a periodate oxidation-based method to selectively enrich Mimivirus surface glycoproteins. 26757703 2 0 theme community 413:421 arg1 composition 345:355 the taxonomic composition 331:355 the taxonomic composition 331:355 Use of unbiased RNA-sequencing can reveal both the taxonomic composition and active biochemical functions of a complex microbial community. 26757703 2 0 theme community 413:421 arg1 functions 380:388 active biochemical functions 361:388 active biochemical functions 361:388 Use of unbiased RNA-sequencing can reveal both the taxonomic composition and active biochemical functions of a complex microbial community. 26757703 6 1 theme Sequence 1009:1016 arg1 searches 1029:1036 Sequence similarity searches 1009:1036 Sequence similarity searches 1009:1036 Sequence similarity searches allowed annotation of 19 to 76% of putative messenger RNA (mRNA) reads, with the highest frequency in the kimchi dataset due to its relatively low complexity and availability of closely related reference genomes. 26757703 4 2 theme pipelines 676:684 arg1 ability 660:666 the ability 656:666 the ability of such pipelines to deliver biologically meaningful insights on microbiome function 656:751 Systematic studies that compare data across microbiomes are needed to demonstrate the ability of such pipelines to deliver biologically meaningful insights on microbiome function. 26757703 2 3 theme taxonomic 335:343 arg1 composition 345:355 the taxonomic composition 331:355 the taxonomic composition 331:355 Use of unbiased RNA-sequencing can reveal both the taxonomic composition and active biochemical functions of a complex microbial community. 26757703 9 4 theme unique 1804:1809 arg1 functions 1811:1819 unique functions 1804:1819 unique functions 1804:1819 Integrating taxonomic and functional annotations within a novel visualization framework revealed the contribution of different taxa to metabolic pathways, allowing the identification of taxa that contribute unique functions. 26757703 5 5 theme large 927:931 arg1 intestine 933:941 mouse large intestine 921:941 mouse large intestine 921:941 RESULTS Here, we apply a standardized analytical pipeline to perform a comparative analysis of metatranscriptomic data from diverse microbial communities derived from mouse large intestine, cow rumen, kimchi culture, deep-sea thermal vent and permafrost. 26757703 6 6 theme genomes 1242:1248 arg1 availability 1200:1211 availability 1200:1211 availability 1200:1211 Sequence similarity searches allowed annotation of 19 to 76% of putative messenger RNA (mRNA) reads, with the highest frequency in the kimchi dataset due to its relatively low complexity and availability of closely related reference genomes. 26757703 6 6 theme genomes 1242:1248 arg1 complexity 1185:1194 its relatively low complexity 1166:1194 its relatively low complexity 1166:1194 Sequence similarity searches allowed annotation of 19 to 76% of putative messenger RNA (mRNA) reads, with the highest frequency in the kimchi dataset due to its relatively low complexity and availability of closely related reference genomes. 26757703 13 7 dep //www.compsysbio.org/microbiome 2559:2589 arg1 http 2554:2557 http 2554:2557 http 2554:2557 The pipeline used in these analyses along with a tutorial has been made freely available for download from our project website: http://www.compsysbio.org/microbiome . 26757703 2 8 theme biochemical 368:378 arg1 functions 380:388 active biochemical functions 361:388 active biochemical functions 361:388 Use of unbiased RNA-sequencing can reveal both the taxonomic composition and active biochemical functions of a complex microbial community. 26757703 12 9 theme downstream 2383:2392 arg1 analyses 2416:2423 downstream, microbiome-specific, analyses 2383:2423 analyses 2416:2423 Consequently, beyond the application of standardized pipelines, additional caution must be taken when interpreting their output and performing downstream, microbiome-specific, analyses. 26757703 1 10 theme complex 239:245 arg1 communities 257:267 complex microbial communities 239:267 complex microbial communities (microbiomes) 239:281 BACKGROUND Metatranscriptomics is emerging as a powerful technology for the functional characterization of complex microbial communities (microbiomes). 26757703 1 10 theme complex 239:245 arg1 microbiomes 270:280 microbiomes 270:280 microbiomes 270:280 BACKGROUND Metatranscriptomics is emerging as a powerful technology for the functional characterization of complex microbial communities (microbiomes). 26757703 6 11 theme related 1224:1230 arg1 genomes 1242:1248 closely related reference genomes 1216:1248 closely related reference genomes 1216:1248 Sequence similarity searches allowed annotation of 19 to 76% of putative messenger RNA (mRNA) reads, with the highest frequency in the kimchi dataset due to its relatively low complexity and availability of closely related reference genomes. 26757703 12 12 theme pipelines 2293:2301 arg1 application 2265:2275 the application 2261:2275 the application of standardized pipelines 2261:2301 Consequently, beyond the application of standardized pipelines, additional caution must be taken when interpreting their output and performing downstream, microbiome-specific, analyses. 26757703 5 13 from analysis 837:844 arg1 communities 896:906 diverse microbial communities 878:906 diverse microbial communities derived from mouse large intestine, cow rumen, kimchi culture, deep-sea thermal vent and permafrost 878:1006 RESULTS Here, we apply a standardized analytical pipeline to perform a comparative analysis of metatranscriptomic data from diverse microbial communities derived from mouse large intestine, cow rumen, kimchi culture, deep-sea thermal vent and permafrost. 26757703 10 14 theme single 1855:1860 arg1 pipeline 1872:1879 a single, standard pipeline 1853:1879 a single, standard pipeline 1853:1879 CONCLUSIONS The application of a single, standard pipeline confirms that the rich taxonomic and functional diversity observed across microbiomes is not simply an artefact of different analysis pipelines but instead reflects distinct environmental influences. 26757703 1 15 theme communities 257:267 arg1 characterization 219:234 the functional characterization 204:234 the functional characterization of complex microbial communities (microbiomes) 204:281 BACKGROUND Metatranscriptomics is emerging as a powerful technology for the functional characterization of complex microbial communities (microbiomes). 26757703 11 16 theme metatranscriptomes 2220:2237 arg1 annotation 2206:2215 comprehensive annotation 2192:2215 comprehensive annotation of metatranscriptomes 2192:2237 At the same time, our findings show how microbiome complexity and availability of reference genomes can impact comprehensive annotation of metatranscriptomes. 26757703 12 17 theme additional 2304:2313 arg1 caution 2315:2321 additional caution 2304:2321 additional caution 2304:2321 Consequently, beyond the application of standardized pipelines, additional caution must be taken when interpreting their output and performing downstream, microbiome-specific, analyses. 26757703 11 18 theme comprehensive 2192:2204 arg1 annotation 2206:2215 comprehensive annotation 2192:2215 comprehensive annotation of metatranscriptomes 2192:2237 At the same time, our findings show how microbiome complexity and availability of reference genomes can impact comprehensive annotation of metatranscriptomes. 26757703 5 19 theme kimchi 955:960 arg1 culture 962:968 kimchi culture 955:968 kimchi culture 955:968 RESULTS Here, we apply a standardized analytical pipeline to perform a comparative analysis of metatranscriptomic data from diverse microbial communities derived from mouse large intestine, cow rumen, kimchi culture, deep-sea thermal vent and permafrost. 26757703 8 20 theme degradation 1563:1573 arg1 cow 1585:1587 cow rumen 1585:1593 cow rumen 1585:1593 From a metabolic perspective, we identified a common core of enzymes involved in amino acid, energy and nucleotide metabolism and also identified microbiome-specific pathways such as phosphonate metabolism (deep sea) and glycan degradation pathways (cow rumen). 26757703 8 20 theme degradation 1563:1573 arg1 pathways 1575:1582 glycan degradation pathways 1556:1582 glycan degradation pathways (cow rumen) 1556:1594 From a metabolic perspective, we identified a common core of enzymes involved in amino acid, energy and nucleotide metabolism and also identified microbiome-specific pathways such as phosphonate metabolism (deep sea) and glycan degradation pathways (cow rumen). 26757703 8 21 theme enzymes 1396:1402 arg1 core 1388:1391 a common core 1379:1391 a common core of enzymes involved in amino acid, energy and nucleotide metabolism 1379:1459 From a metabolic perspective, we identified a common core of enzymes involved in amino acid, energy and nucleotide metabolism and also identified microbiome-specific pathways such as phosphonate metabolism (deep sea) and glycan degradation pathways (cow rumen). 26757703 9 22 theme Integrating 1597:1607 arg1 annotations 1634:1644 Integrating taxonomic and functional annotations 1597:1644 Integrating taxonomic and functional annotations within a novel visualization framework 1597:1683 Integrating taxonomic and functional annotations within a novel visualization framework revealed the contribution of different taxa to metabolic pathways, allowing the identification of taxa that contribute unique functions. 26757703 6 23 dep 76 1066:1067 arg1 to 1063:1064 to 1063:1064 to 1063:1064 Sequence similarity searches allowed annotation of 19 to 76% of putative messenger RNA (mRNA) reads, with the highest frequency in the kimchi dataset due to its relatively low complexity and availability of closely related reference genomes. 26757703 5 24 theme standardized 779:790 arg1 pipeline 803:810 a standardized analytical pipeline 777:810 a standardized analytical pipeline to perform a comparative analysis of metatranscriptomic data from diverse microbial communities derived from mouse large intestine, cow rumen, kimchi culture, deep-sea thermal vent and permafrost 777:1006 RESULTS Here, we apply a standardized analytical pipeline to perform a comparative analysis of metatranscriptomic data from diverse microbial communities derived from mouse large intestine, cow rumen, kimchi culture, deep-sea thermal vent and permafrost. 26757703 11 25 theme genomes 2173:2179 arg1 complexity 2132:2141 microbiome complexity 2121:2141 microbiome complexity 2121:2141 At the same time, our findings show how microbiome complexity and availability of reference genomes can impact comprehensive annotation of metatranscriptomes. 26757703 11 25 theme genomes 2173:2179 arg1 availability 2147:2158 availability 2147:2158 availability 2147:2158 At the same time, our findings show how microbiome complexity and availability of reference genomes can impact comprehensive annotation of metatranscriptomes. 26757703 0 26 theme metabolic 74:82 arg1 pathways 84:91 core metabolic pathways 69:91 core metabolic pathways 69:91 Metatranscriptomic analysis of diverse microbial communities reveals core metabolic pathways and microbiome-specific functionality. 26757703 2 27 theme unbiased 291:298 arg1 RNA-sequencing 300:313 unbiased RNA-sequencing 291:313 unbiased RNA-sequencing 291:313 Use of unbiased RNA-sequencing can reveal both the taxonomic composition and active biochemical functions of a complex microbial community. 26757703 4 28 theme Systematic 574:583 arg1 studies 585:591 Systematic studies 574:591 Systematic studies that compare data across microbiomes 574:628 Systematic studies that compare data across microbiomes are needed to demonstrate the ability of such pipelines to deliver biologically meaningful insights on microbiome function. 26757703 5 29 theme diverse 878:884 arg1 communities 896:906 diverse microbial communities 878:906 diverse microbial communities derived from mouse large intestine, cow rumen, kimchi culture, deep-sea thermal vent and permafrost 878:1006 RESULTS Here, we apply a standardized analytical pipeline to perform a comparative analysis of metatranscriptomic data from diverse microbial communities derived from mouse large intestine, cow rumen, kimchi culture, deep-sea thermal vent and permafrost. 26757703 8 30 theme nucleotide 1439:1448 arg1 metabolism 1450:1459 nucleotide metabolism 1439:1459 nucleotide metabolism 1439:1459 From a metabolic perspective, we identified a common core of enzymes involved in amino acid, energy and nucleotide metabolism and also identified microbiome-specific pathways such as phosphonate metabolism (deep sea) and glycan degradation pathways (cow rumen). 26757703 5 31 theme comparative 825:835 arg1 analysis 837:844 a comparative analysis 823:844 a comparative analysis of metatranscriptomic data from diverse microbial communities derived from mouse large intestine, cow rumen, kimchi culture, deep-sea thermal vent and permafrost 823:1006 RESULTS Here, we apply a standardized analytical pipeline to perform a comparative analysis of metatranscriptomic data from diverse microbial communities derived from mouse large intestine, cow rumen, kimchi culture, deep-sea thermal vent and permafrost. 26757703 9 32 theme visualization 1661:1673 arg1 framework 1675:1683 a novel visualization framework 1653:1683 a novel visualization framework 1653:1683 Integrating taxonomic and functional annotations within a novel visualization framework revealed the contribution of different taxa to metabolic pathways, allowing the identification of taxa that contribute unique functions. 26757703 6 33 theme messenger 1082:1090 arg1 mRNA 1097:1100 mRNA 1097:1100 mRNA 1097:1100 Sequence similarity searches allowed annotation of 19 to 76% of putative messenger RNA (mRNA) reads, with the highest frequency in the kimchi dataset due to its relatively low complexity and availability of closely related reference genomes. 26757703 6 33 theme messenger 1082:1090 arg1 RNA 1092:1094 putative messenger RNA 1073:1094 putative messenger RNA (mRNA) reads, with the highest frequency in the kimchi dataset due to its relatively low complexity and availability of closely related reference genomes 1073:1248 Sequence similarity searches allowed annotation of 19 to 76% of putative messenger RNA (mRNA) reads, with the highest frequency in the kimchi dataset due to its relatively low complexity and availability of closely related reference genomes. 26757703 3 34 theme pipelines 500:508 arg1 lack 437:440 the lack 433:440 the lack of established reference genomes, computational tools and pipelines 433:508 However, the lack of established reference genomes, computational tools and pipelines make analysis and interpretation of these datasets challenging. 26757703 7 35 theme taxonomic 1298:1306 arg1 signatures 1323:1332 distinct taxonomic and functional signatures 1289:1332 distinct taxonomic and functional signatures 1289:1332 Metatranscriptomic datasets exhibited distinct taxonomic and functional signatures. 26757703 0 36 theme communities 49:59 arg1 analysis 19:26 Metatranscriptomic analysis 0:26 Metatranscriptomic analysis of diverse microbial communities 0:59 Metatranscriptomic analysis of diverse microbial communities reveals core metabolic pathways and microbiome-specific functionality. 26757703 3 37 theme tools 490:494 arg1 lack 437:440 the lack 433:440 the lack of established reference genomes, computational tools and pipelines 433:508 However, the lack of established reference genomes, computational tools and pipelines make analysis and interpretation of these datasets challenging. 26757703 0 38 theme Metatranscriptomic 0:17 arg1 analysis 19:26 Metatranscriptomic analysis 0:26 Metatranscriptomic analysis of diverse microbial communities 0:59 Metatranscriptomic analysis of diverse microbial communities reveals core metabolic pathways and microbiome-specific functionality. 26757703 11 39 theme microbiome 2121:2130 arg1 complexity 2132:2141 microbiome complexity 2121:2141 microbiome complexity 2121:2141 At the same time, our findings show how microbiome complexity and availability of reference genomes can impact comprehensive annotation of metatranscriptomes. 26757703 7 40 theme Metatranscriptomic 1251:1268 arg1 datasets 1270:1277 Metatranscriptomic datasets 1251:1277 Metatranscriptomic datasets 1251:1277 Metatranscriptomic datasets exhibited distinct taxonomic and functional signatures. 26757703 9 41 theme different 1714:1722 arg1 taxa 1724:1727 different taxa 1714:1727 different taxa 1714:1727 Integrating taxonomic and functional annotations within a novel visualization framework revealed the contribution of different taxa to metabolic pathways, allowing the identification of taxa that contribute unique functions. 26757703 9 42 theme functional 1623:1632 arg1 annotations 1634:1644 Integrating taxonomic and functional annotations 1597:1644 Integrating taxonomic and functional annotations within a novel visualization framework 1597:1683 Integrating taxonomic and functional annotations within a novel visualization framework revealed the contribution of different taxa to metabolic pathways, allowing the identification of taxa that contribute unique functions. 26757703 10 43 theme analysis 2006:2013 arg1 pipelines 2015:2023 different analysis pipelines 1996:2023 different analysis pipelines 1996:2023 CONCLUSIONS The application of a single, standard pipeline confirms that the rich taxonomic and functional diversity observed across microbiomes is not simply an artefact of different analysis pipelines but instead reflects distinct environmental influences. 26757703 0 44 theme microbial 39:47 arg1 communities 49:59 diverse microbial communities 31:59 diverse microbial communities 31:59 Metatranscriptomic analysis of diverse microbial communities reveals core metabolic pathways and microbiome-specific functionality. 26757703 3 45 theme reference 457:465 arg1 genomes 467:473 established reference genomes 445:473 established reference genomes 445:473 However, the lack of established reference genomes, computational tools and pipelines make analysis and interpretation of these datasets challenging. 26757703 5 46 theme data 868:871 arg1 analysis 837:844 a comparative analysis 823:844 a comparative analysis of metatranscriptomic data from diverse microbial communities derived from mouse large intestine, cow rumen, kimchi culture, deep-sea thermal vent and permafrost 823:1006 RESULTS Here, we apply a standardized analytical pipeline to perform a comparative analysis of metatranscriptomic data from diverse microbial communities derived from mouse large intestine, cow rumen, kimchi culture, deep-sea thermal vent and permafrost. 26757703 10 47 dep CONCLUSIONS 1822:1832 arg1 confirms 1881:1888 confirms 1881:1888 confirms that the rich taxonomic and functional diversity observed across microbiomes is not simply an artefact of different analysis pipelines but instead reflects distinct environmental influences 1881:2078 CONCLUSIONS The application of a single, standard pipeline confirms that the rich taxonomic and functional diversity observed across microbiomes is not simply an artefact of different analysis pipelines but instead reflects distinct environmental influences. 26757703 2 48 theme microbial 403:411 arg1 community 413:421 a complex microbial community 393:421 a complex microbial community 393:421 Use of unbiased RNA-sequencing can reveal both the taxonomic composition and active biochemical functions of a complex microbial community. 26757703 8 49 theme deep 1542:1545 arg1 metabolism 1530:1539 phosphonate metabolism 1518:1539 phosphonate metabolism (deep sea) 1518:1550 From a metabolic perspective, we identified a common core of enzymes involved in amino acid, energy and nucleotide metabolism and also identified microbiome-specific pathways such as phosphonate metabolism (deep sea) and glycan degradation pathways (cow rumen). 26757703 8 49 theme deep 1542:1545 arg1 sea 1547:1549 deep sea 1542:1549 deep sea 1542:1549 From a metabolic perspective, we identified a common core of enzymes involved in amino acid, energy and nucleotide metabolism and also identified microbiome-specific pathways such as phosphonate metabolism (deep sea) and glycan degradation pathways (cow rumen). 26757703 11 50 theme reference 2163:2171 arg1 genomes 2173:2179 reference genomes 2163:2179 reference genomes 2163:2179 At the same time, our findings show how microbiome complexity and availability of reference genomes can impact comprehensive annotation of metatranscriptomes. 26757703 10 51 theme pipeline 1872:1879 arg1 application 1838:1848 The application 1834:1848 The application of a single, standard pipeline 1834:1879 CONCLUSIONS The application of a single, standard pipeline confirms that the rich taxonomic and functional diversity observed across microbiomes is not simply an artefact of different analysis pipelines but instead reflects distinct environmental influences. 26757703 13 52 theme project 2537:2543 arg1 website 2545:2551 our project website 2533:2551 our project website 2533:2551 The pipeline used in these analyses along with a tutorial has been made freely available for download from our project website: http://www.compsysbio.org/microbiome . 26757703 6 53 theme similarity 1018:1027 arg1 searches 1029:1036 Sequence similarity searches 1009:1036 Sequence similarity searches 1009:1036 Sequence similarity searches allowed annotation of 19 to 76% of putative messenger RNA (mRNA) reads, with the highest frequency in the kimchi dataset due to its relatively low complexity and availability of closely related reference genomes. 26757703 9 54 theme taxa 1783:1786 arg1 identification 1765:1778 the identification 1761:1778 the identification of taxa that contribute unique functions 1761:1819 Integrating taxonomic and functional annotations within a novel visualization framework revealed the contribution of different taxa to metabolic pathways, allowing the identification of taxa that contribute unique functions. 26757703 10 55 theme environmental 2055:2067 arg1 influences 2069:2078 distinct environmental influences 2046:2078 distinct environmental influences 2046:2078 CONCLUSIONS The application of a single, standard pipeline confirms that the rich taxonomic and functional diversity observed across microbiomes is not simply an artefact of different analysis pipelines but instead reflects distinct environmental influences. 26757703 10 56 theme rich 1899:1902 arg1 artefact 1984:1991 an artefact 1981:1991 an artefact of different analysis pipelines 1981:2023 CONCLUSIONS The application of a single, standard pipeline confirms that the rich taxonomic and functional diversity observed across microbiomes is not simply an artefact of different analysis pipelines but instead reflects distinct environmental influences. 26757703 10 56 theme rich 1899:1902 arg1 diversity 1929:1937 the rich taxonomic and functional diversity 1895:1937 the rich taxonomic and functional diversity observed across microbiomes 1895:1965 CONCLUSIONS The application of a single, standard pipeline confirms that the rich taxonomic and functional diversity observed across microbiomes is not simply an artefact of different analysis pipelines but instead reflects distinct environmental influences. 26757703 4 57 theme such 671:674 arg1 pipelines 676:684 such pipelines 671:684 such pipelines 671:684 Systematic studies that compare data across microbiomes are needed to demonstrate the ability of such pipelines to deliver biologically meaningful insights on microbiome function. 26757703 1 58 theme functional 208:217 arg1 characterization 219:234 the functional characterization 204:234 the functional characterization of complex microbial communities (microbiomes) 204:281 BACKGROUND Metatranscriptomics is emerging as a powerful technology for the functional characterization of complex microbial communities (microbiomes). 26757703 8 59 theme metabolic 1342:1350 arg1 perspective 1352:1362 a metabolic perspective 1340:1362 a metabolic perspective 1340:1362 From a metabolic perspective, we identified a common core of enzymes involved in amino acid, energy and nucleotide metabolism and also identified microbiome-specific pathways such as phosphonate metabolism (deep sea) and glycan degradation pathways (cow rumen). 26757703 5 60 theme deep-sea 971:978 arg1 vent 988:991 deep-sea thermal vent 971:991 deep-sea thermal vent 971:991 RESULTS Here, we apply a standardized analytical pipeline to perform a comparative analysis of metatranscriptomic data from diverse microbial communities derived from mouse large intestine, cow rumen, kimchi culture, deep-sea thermal vent and permafrost. 26757703 6 61 theme putative 1073:1080 arg1 mRNA 1097:1100 mRNA 1097:1100 mRNA 1097:1100 Sequence similarity searches allowed annotation of 19 to 76% of putative messenger RNA (mRNA) reads, with the highest frequency in the kimchi dataset due to its relatively low complexity and availability of closely related reference genomes. 26757703 6 61 theme putative 1073:1080 arg1 RNA 1092:1094 putative messenger RNA 1073:1094 putative messenger RNA (mRNA) reads, with the highest frequency in the kimchi dataset due to its relatively low complexity and availability of closely related reference genomes 1073:1248 Sequence similarity searches allowed annotation of 19 to 76% of putative messenger RNA (mRNA) reads, with the highest frequency in the kimchi dataset due to its relatively low complexity and availability of closely related reference genomes. 26757703 6 62 theme reference 1232:1240 arg1 genomes 1242:1248 closely related reference genomes 1216:1248 closely related reference genomes 1216:1248 Sequence similarity searches allowed annotation of 19 to 76% of putative messenger RNA (mRNA) reads, with the highest frequency in the kimchi dataset due to its relatively low complexity and availability of closely related reference genomes. 26757703 5 63 theme analytical 792:801 arg1 pipeline 803:810 a standardized analytical pipeline 777:810 a standardized analytical pipeline to perform a comparative analysis of metatranscriptomic data from diverse microbial communities derived from mouse large intestine, cow rumen, kimchi culture, deep-sea thermal vent and permafrost 777:1006 RESULTS Here, we apply a standardized analytical pipeline to perform a comparative analysis of metatranscriptomic data from diverse microbial communities derived from mouse large intestine, cow rumen, kimchi culture, deep-sea thermal vent and permafrost. 26757703 5 64 attach derived 908:914 arg1 rumen 948:952 cow rumen 944:952 cow rumen 944:952 RESULTS Here, we apply a standardized analytical pipeline to perform a comparative analysis of metatranscriptomic data from diverse microbial communities derived from mouse large intestine, cow rumen, kimchi culture, deep-sea thermal vent and permafrost. 26757703 5 64 attach derived 908:914 arg1 vent 988:991 deep-sea thermal vent 971:991 deep-sea thermal vent 971:991 RESULTS Here, we apply a standardized analytical pipeline to perform a comparative analysis of metatranscriptomic data from diverse microbial communities derived from mouse large intestine, cow rumen, kimchi culture, deep-sea thermal vent and permafrost. 26757703 5 64 attach derived 908:914 arg2 communities 896:906 diverse microbial communities 878:906 diverse microbial communities derived from mouse large intestine, cow rumen, kimchi culture, deep-sea thermal vent and permafrost 878:1006 RESULTS Here, we apply a standardized analytical pipeline to perform a comparative analysis of metatranscriptomic data from diverse microbial communities derived from mouse large intestine, cow rumen, kimchi culture, deep-sea thermal vent and permafrost. 26757703 5 64 attach derived 908:914 arg1 permafrost 997:1006 permafrost 997:1006 permafrost 997:1006 RESULTS Here, we apply a standardized analytical pipeline to perform a comparative analysis of metatranscriptomic data from diverse microbial communities derived from mouse large intestine, cow rumen, kimchi culture, deep-sea thermal vent and permafrost. 26757703 5 64 attach derived 908:914 arg1 intestine 933:941 mouse large intestine 921:941 mouse large intestine 921:941 RESULTS Here, we apply a standardized analytical pipeline to perform a comparative analysis of metatranscriptomic data from diverse microbial communities derived from mouse large intestine, cow rumen, kimchi culture, deep-sea thermal vent and permafrost. 26757703 5 64 attach derived 908:914 arg1 culture 962:968 kimchi culture 955:968 kimchi culture 955:968 RESULTS Here, we apply a standardized analytical pipeline to perform a comparative analysis of metatranscriptomic data from diverse microbial communities derived from mouse large intestine, cow rumen, kimchi culture, deep-sea thermal vent and permafrost. 26757703 2 65 theme active 361:366 arg1 functions 380:388 active biochemical functions 361:388 active biochemical functions 361:388 Use of unbiased RNA-sequencing can reveal both the taxonomic composition and active biochemical functions of a complex microbial community. 26757703 1 66 theme microbial 247:255 arg1 communities 257:267 complex microbial communities 239:267 complex microbial communities (microbiomes) 239:281 BACKGROUND Metatranscriptomics is emerging as a powerful technology for the functional characterization of complex microbial communities (microbiomes). 26757703 1 66 theme microbial 247:255 arg1 microbiomes 270:280 microbiomes 270:280 microbiomes 270:280 BACKGROUND Metatranscriptomics is emerging as a powerful technology for the functional characterization of complex microbial communities (microbiomes). 26757703 10 67 theme functional 1918:1927 arg1 artefact 1984:1991 an artefact 1981:1991 an artefact of different analysis pipelines 1981:2023 CONCLUSIONS The application of a single, standard pipeline confirms that the rich taxonomic and functional diversity observed across microbiomes is not simply an artefact of different analysis pipelines but instead reflects distinct environmental influences. 26757703 10 67 theme functional 1918:1927 arg1 diversity 1929:1937 the rich taxonomic and functional diversity 1895:1937 the rich taxonomic and functional diversity observed across microbiomes 1895:1965 CONCLUSIONS The application of a single, standard pipeline confirms that the rich taxonomic and functional diversity observed across microbiomes is not simply an artefact of different analysis pipelines but instead reflects distinct environmental influences. 26757703 6 68 theme % 1068:1068 arg1 annotation 1046:1055 annotation 1046:1055 annotation of 19 to 76% of putative messenger RNA (mRNA) reads, with the highest frequency in the kimchi dataset due to its relatively low complexity and availability of closely related reference genomes 1046:1248 Sequence similarity searches allowed annotation of 19 to 76% of putative messenger RNA (mRNA) reads, with the highest frequency in the kimchi dataset due to its relatively low complexity and availability of closely related reference genomes. 26757703 8 69 theme glycan 1556:1561 arg1 cow 1585:1587 cow rumen 1585:1593 cow rumen 1585:1593 From a metabolic perspective, we identified a common core of enzymes involved in amino acid, energy and nucleotide metabolism and also identified microbiome-specific pathways such as phosphonate metabolism (deep sea) and glycan degradation pathways (cow rumen). 26757703 8 69 theme glycan 1556:1561 arg1 pathways 1575:1582 glycan degradation pathways 1556:1582 glycan degradation pathways (cow rumen) 1556:1594 From a metabolic perspective, we identified a common core of enzymes involved in amino acid, energy and nucleotide metabolism and also identified microbiome-specific pathways such as phosphonate metabolism (deep sea) and glycan degradation pathways (cow rumen). 26757703 12 70 theme standardized 2280:2291 arg1 pipelines 2293:2301 standardized pipelines 2280:2301 standardized pipelines 2280:2301 Consequently, beyond the application of standardized pipelines, additional caution must be taken when interpreting their output and performing downstream, microbiome-specific, analyses. 26757703 4 71 from insights 721:728 arg1 function 744:751 microbiome function 733:751 microbiome function 733:751 Systematic studies that compare data across microbiomes are needed to demonstrate the ability of such pipelines to deliver biologically meaningful insights on microbiome function. 26757703 8 72 theme common 1381:1386 arg1 core 1388:1391 a common core 1379:1391 a common core of enzymes involved in amino acid, energy and nucleotide metabolism 1379:1459 From a metabolic perspective, we identified a common core of enzymes involved in amino acid, energy and nucleotide metabolism and also identified microbiome-specific pathways such as phosphonate metabolism (deep sea) and glycan degradation pathways (cow rumen). 26757703 6 73 from frequency 1127:1135 arg1 dataset 1151:1157 the kimchi dataset 1140:1157 the kimchi dataset due to its relatively low complexity and availability of closely related reference genomes 1140:1248 Sequence similarity searches allowed annotation of 19 to 76% of putative messenger RNA (mRNA) reads, with the highest frequency in the kimchi dataset due to its relatively low complexity and availability of closely related reference genomes. 26757703 9 74 theme taxonomic 1609:1617 arg1 annotations 1634:1644 Integrating taxonomic and functional annotations 1597:1644 Integrating taxonomic and functional annotations within a novel visualization framework 1597:1683 Integrating taxonomic and functional annotations within a novel visualization framework revealed the contribution of different taxa to metabolic pathways, allowing the identification of taxa that contribute unique functions. 26757703 5 75 theme thermal 980:986 arg1 vent 988:991 deep-sea thermal vent 971:991 deep-sea thermal vent 971:991 RESULTS Here, we apply a standardized analytical pipeline to perform a comparative analysis of metatranscriptomic data from diverse microbial communities derived from mouse large intestine, cow rumen, kimchi culture, deep-sea thermal vent and permafrost. 26757703 5 76 theme metatranscriptomic 849:866 arg1 data 868:871 metatranscriptomic data 849:871 metatranscriptomic data from diverse microbial communities derived from mouse large intestine, cow rumen, kimchi culture, deep-sea thermal vent and permafrost 849:1006 RESULTS Here, we apply a standardized analytical pipeline to perform a comparative analysis of metatranscriptomic data from diverse microbial communities derived from mouse large intestine, cow rumen, kimchi culture, deep-sea thermal vent and permafrost. 26757703 2 77 theme RNA-sequencing 300:313 arg1 Use 284:286 Use 284:286 Use of unbiased RNA-sequencing 284:313 Use of unbiased RNA-sequencing can reveal both the taxonomic composition and active biochemical functions of a complex microbial community. 26757703 5 78 theme cow 944:946 arg1 rumen 948:952 cow rumen 944:952 cow rumen 944:952 RESULTS Here, we apply a standardized analytical pipeline to perform a comparative analysis of metatranscriptomic data from diverse microbial communities derived from mouse large intestine, cow rumen, kimchi culture, deep-sea thermal vent and permafrost. 26757703 1 79 theme powerful 180:187 arg1 technology 189:198 a powerful technology 178:198 a powerful technology for the functional characterization of complex microbial communities (microbiomes) 178:281 BACKGROUND Metatranscriptomics is emerging as a powerful technology for the functional characterization of complex microbial communities (microbiomes). 26757703 6 80 dep RNA 1092:1094 arg1 reads 1103:1107 reads 1103:1107 reads 1103:1107 Sequence similarity searches allowed annotation of 19 to 76% of putative messenger RNA (mRNA) reads, with the highest frequency in the kimchi dataset due to its relatively low complexity and availability of closely related reference genomes. 26757703 8 81 theme amino 1416:1420 arg1 acid 1422:1425 amino acid 1416:1425 amino acid 1416:1425 From a metabolic perspective, we identified a common core of enzymes involved in amino acid, energy and nucleotide metabolism and also identified microbiome-specific pathways such as phosphonate metabolism (deep sea) and glycan degradation pathways (cow rumen). 26757703 7 82 theme functional 1312:1321 arg1 signatures 1323:1332 distinct taxonomic and functional signatures 1289:1332 distinct taxonomic and functional signatures 1289:1332 Metatranscriptomic datasets exhibited distinct taxonomic and functional signatures. 26757703 0 83 theme microbiome-specific 97:115 arg1 functionality 117:129 microbiome-specific functionality 97:129 microbiome-specific functionality 97:129 Metatranscriptomic analysis of diverse microbial communities reveals core metabolic pathways and microbiome-specific functionality. 26757703 5 84 from communities 896:906 arg1 analysis 837:844 a comparative analysis 823:844 a comparative analysis of metatranscriptomic data from diverse microbial communities derived from mouse large intestine, cow rumen, kimchi culture, deep-sea thermal vent and permafrost 823:1006 RESULTS Here, we apply a standardized analytical pipeline to perform a comparative analysis of metatranscriptomic data from diverse microbial communities derived from mouse large intestine, cow rumen, kimchi culture, deep-sea thermal vent and permafrost. 26757703 5 84 from communities 896:906 arg1 data 868:871 metatranscriptomic data 849:871 metatranscriptomic data from diverse microbial communities derived from mouse large intestine, cow rumen, kimchi culture, deep-sea thermal vent and permafrost 849:1006 RESULTS Here, we apply a standardized analytical pipeline to perform a comparative analysis of metatranscriptomic data from diverse microbial communities derived from mouse large intestine, cow rumen, kimchi culture, deep-sea thermal vent and permafrost. 26757703 9 85 theme novel 1655:1659 arg1 framework 1675:1683 a novel visualization framework 1653:1683 a novel visualization framework 1653:1683 Integrating taxonomic and functional annotations within a novel visualization framework revealed the contribution of different taxa to metabolic pathways, allowing the identification of taxa that contribute unique functions. 26757703 10 86 theme taxonomic 1904:1912 arg1 artefact 1984:1991 an artefact 1981:1991 an artefact of different analysis pipelines 1981:2023 CONCLUSIONS The application of a single, standard pipeline confirms that the rich taxonomic and functional diversity observed across microbiomes is not simply an artefact of different analysis pipelines but instead reflects distinct environmental influences. 26757703 10 86 theme taxonomic 1904:1912 arg1 diversity 1929:1937 the rich taxonomic and functional diversity 1895:1937 the rich taxonomic and functional diversity observed across microbiomes 1895:1965 CONCLUSIONS The application of a single, standard pipeline confirms that the rich taxonomic and functional diversity observed across microbiomes is not simply an artefact of different analysis pipelines but instead reflects distinct environmental influences. 26757703 6 87 theme RNA 1092:1094 arg1 % 1068:1068 19 to 76% 1060:1068 19 to 76% of putative messenger RNA (mRNA) reads, with the highest frequency in the kimchi dataset due to its relatively low complexity and availability of closely related reference genomes 1060:1248 Sequence similarity searches allowed annotation of 19 to 76% of putative messenger RNA (mRNA) reads, with the highest frequency in the kimchi dataset due to its relatively low complexity and availability of closely related reference genomes. 26757703 6 87 theme RNA 1092:1094 arg1 mRNA 1097:1100 mRNA 1097:1100 mRNA 1097:1100 Sequence similarity searches allowed annotation of 19 to 76% of putative messenger RNA (mRNA) reads, with the highest frequency in the kimchi dataset due to its relatively low complexity and availability of closely related reference genomes. 26757703 6 87 theme RNA 1092:1094 arg1 RNA 1092:1094 putative messenger RNA 1073:1094 putative messenger RNA (mRNA) reads, with the highest frequency in the kimchi dataset due to its relatively low complexity and availability of closely related reference genomes 1073:1248 Sequence similarity searches allowed annotation of 19 to 76% of putative messenger RNA (mRNA) reads, with the highest frequency in the kimchi dataset due to its relatively low complexity and availability of closely related reference genomes. 26757703 10 88 dep single 1855:1860 arg1 standard 1863:1870 standard 1863:1870 standard 1863:1870 CONCLUSIONS The application of a single, standard pipeline confirms that the rich taxonomic and functional diversity observed across microbiomes is not simply an artefact of different analysis pipelines but instead reflects distinct environmental influences. 26757703 7 89 theme distinct 1289:1296 arg1 signatures 1323:1332 distinct taxonomic and functional signatures 1289:1332 distinct taxonomic and functional signatures 1289:1332 Metatranscriptomic datasets exhibited distinct taxonomic and functional signatures. 26757703 12 90 dep downstream 2383:2392 arg1 microbiome-specific 2395:2413 microbiome-specific 2395:2413 microbiome-specific 2395:2413 Consequently, beyond the application of standardized pipelines, additional caution must be taken when interpreting their output and performing downstream, microbiome-specific, analyses. 26757703 6 91 theme due 1159:1161 arg1 dataset 1151:1157 the kimchi dataset 1140:1157 the kimchi dataset due to its relatively low complexity and availability of closely related reference genomes 1140:1248 Sequence similarity searches allowed annotation of 19 to 76% of putative messenger RNA (mRNA) reads, with the highest frequency in the kimchi dataset due to its relatively low complexity and availability of closely related reference genomes. 26757703 5 92 theme mouse 921:925 arg1 intestine 933:941 mouse large intestine 921:941 mouse large intestine 921:941 RESULTS Here, we apply a standardized analytical pipeline to perform a comparative analysis of metatranscriptomic data from diverse microbial communities derived from mouse large intestine, cow rumen, kimchi culture, deep-sea thermal vent and permafrost. 26757703 6 93 theme kimchi 1144:1149 arg1 dataset 1151:1157 the kimchi dataset 1140:1157 the kimchi dataset due to its relatively low complexity and availability of closely related reference genomes 1140:1248 Sequence similarity searches allowed annotation of 19 to 76% of putative messenger RNA (mRNA) reads, with the highest frequency in the kimchi dataset due to its relatively low complexity and availability of closely related reference genomes. 26757703 3 94 theme established 445:455 arg1 genomes 467:473 established reference genomes 445:473 established reference genomes 445:473 However, the lack of established reference genomes, computational tools and pipelines make analysis and interpretation of these datasets challenging. 26757703 0 95 theme diverse 31:37 arg1 communities 49:59 diverse microbial communities 31:59 diverse microbial communities 31:59 Metatranscriptomic analysis of diverse microbial communities reveals core metabolic pathways and microbiome-specific functionality. 26757703 1 96 theme BACKGROUND 132:141 arg1 Metatranscriptomics 143:161 BACKGROUND Metatranscriptomics 132:161 BACKGROUND Metatranscriptomics 132:161 BACKGROUND Metatranscriptomics is emerging as a powerful technology for the functional characterization of complex microbial communities (microbiomes). 26757703 5 97 dep RESULTS 754:760 arg1 apply 771:775 apply 771:775 apply a standardized analytical pipeline to perform a comparative analysis of metatranscriptomic data from diverse microbial communities derived from mouse large intestine, cow rumen, kimchi culture, deep-sea thermal vent and permafrost 771:1006 RESULTS Here, we apply a standardized analytical pipeline to perform a comparative analysis of metatranscriptomic data from diverse microbial communities derived from mouse large intestine, cow rumen, kimchi culture, deep-sea thermal vent and permafrost. 26757703 10 98 theme pipelines 2015:2023 arg1 diversity 1929:1937 the rich taxonomic and functional diversity 1895:1937 the rich taxonomic and functional diversity observed across microbiomes 1895:1965 CONCLUSIONS The application of a single, standard pipeline confirms that the rich taxonomic and functional diversity observed across microbiomes is not simply an artefact of different analysis pipelines but instead reflects distinct environmental influences. 26757703 10 98 theme pipelines 2015:2023 arg1 artefact 1984:1991 an artefact 1981:1991 an artefact of different analysis pipelines 1981:2023 CONCLUSIONS The application of a single, standard pipeline confirms that the rich taxonomic and functional diversity observed across microbiomes is not simply an artefact of different analysis pipelines but instead reflects distinct environmental influences. 26757703 8 99 theme microbiome-specific 1481:1499 arg1 pathways 1575:1582 glycan degradation pathways 1556:1582 glycan degradation pathways (cow rumen) 1556:1594 From a metabolic perspective, we identified a common core of enzymes involved in amino acid, energy and nucleotide metabolism and also identified microbiome-specific pathways such as phosphonate metabolism (deep sea) and glycan degradation pathways (cow rumen). 26757703 8 99 theme microbiome-specific 1481:1499 arg1 metabolism 1530:1539 phosphonate metabolism 1518:1539 phosphonate metabolism (deep sea) 1518:1550 From a metabolic perspective, we identified a common core of enzymes involved in amino acid, energy and nucleotide metabolism and also identified microbiome-specific pathways such as phosphonate metabolism (deep sea) and glycan degradation pathways (cow rumen). 26757703 8 99 theme microbiome-specific 1481:1499 arg1 pathways 1501:1508 microbiome-specific pathways 1481:1508 microbiome-specific pathways such as phosphonate metabolism (deep sea) and glycan degradation pathways (cow rumen) 1481:1594 From a metabolic perspective, we identified a common core of enzymes involved in amino acid, energy and nucleotide metabolism and also identified microbiome-specific pathways such as phosphonate metabolism (deep sea) and glycan degradation pathways (cow rumen). 26757703 5 100 theme microbial 886:894 arg1 communities 896:906 diverse microbial communities 878:906 diverse microbial communities derived from mouse large intestine, cow rumen, kimchi culture, deep-sea thermal vent and permafrost 878:1006 RESULTS Here, we apply a standardized analytical pipeline to perform a comparative analysis of metatranscriptomic data from diverse microbial communities derived from mouse large intestine, cow rumen, kimchi culture, deep-sea thermal vent and permafrost. 26757703 9 101 theme taxa 1724:1727 arg1 contribution 1698:1709 the contribution 1694:1709 the contribution of different taxa to metabolic pathways 1694:1749 Integrating taxonomic and functional annotations within a novel visualization framework revealed the contribution of different taxa to metabolic pathways, allowing the identification of taxa that contribute unique functions. 26757703 6 102 theme highest 1119:1125 arg1 frequency 1127:1135 the highest frequency 1115:1135 the highest frequency in the kimchi dataset due to its relatively low complexity and availability of closely related reference genomes 1115:1248 Sequence similarity searches allowed annotation of 19 to 76% of putative messenger RNA (mRNA) reads, with the highest frequency in the kimchi dataset due to its relatively low complexity and availability of closely related reference genomes. 26757703 3 103 theme computational 476:488 arg1 tools 490:494 computational tools 476:494 computational tools 476:494 However, the lack of established reference genomes, computational tools and pipelines make analysis and interpretation of these datasets challenging. 26757703 10 104 theme different 1996:2004 arg1 pipelines 2015:2023 different analysis pipelines 1996:2023 different analysis pipelines 1996:2023 CONCLUSIONS The application of a single, standard pipeline confirms that the rich taxonomic and functional diversity observed across microbiomes is not simply an artefact of different analysis pipelines but instead reflects distinct environmental influences. 26757703 11 105 theme same 2088:2091 arg1 time 2093:2096 the same time 2084:2096 the same time 2084:2096 At the same time, our findings show how microbiome complexity and availability of reference genomes can impact comprehensive annotation of metatranscriptomes. 26757703 0 106 theme core 69:72 arg1 pathways 84:91 core metabolic pathways 69:91 core metabolic pathways 69:91 Metatranscriptomic analysis of diverse microbial communities reveals core metabolic pathways and microbiome-specific functionality. 26757703 9 107 theme metabolic 1732:1740 arg1 pathways 1742:1749 metabolic pathways 1732:1749 metabolic pathways 1732:1749 Integrating taxonomic and functional annotations within a novel visualization framework revealed the contribution of different taxa to metabolic pathways, allowing the identification of taxa that contribute unique functions. 26757703 3 108 theme genomes 467:473 arg1 lack 437:440 the lack 433:440 the lack of established reference genomes, computational tools and pipelines 433:508 However, the lack of established reference genomes, computational tools and pipelines make analysis and interpretation of these datasets challenging. 26757703 10 109 theme distinct 2046:2053 arg1 influences 2069:2078 distinct environmental influences 2046:2078 distinct environmental influences 2046:2078 CONCLUSIONS The application of a single, standard pipeline confirms that the rich taxonomic and functional diversity observed across microbiomes is not simply an artefact of different analysis pipelines but instead reflects distinct environmental influences. 26757703 8 110 theme phosphonate 1518:1528 arg1 metabolism 1530:1539 phosphonate metabolism 1518:1539 phosphonate metabolism (deep sea) 1518:1550 From a metabolic perspective, we identified a common core of enzymes involved in amino acid, energy and nucleotide metabolism and also identified microbiome-specific pathways such as phosphonate metabolism (deep sea) and glycan degradation pathways (cow rumen). 26757703 8 110 theme phosphonate 1518:1528 arg1 sea 1547:1549 deep sea 1542:1549 deep sea 1542:1549 From a metabolic perspective, we identified a common core of enzymes involved in amino acid, energy and nucleotide metabolism and also identified microbiome-specific pathways such as phosphonate metabolism (deep sea) and glycan degradation pathways (cow rumen). 26757703 2 111 theme complex 395:401 arg1 community 413:421 a complex microbial community 393:421 a complex microbial community 393:421 Use of unbiased RNA-sequencing can reveal both the taxonomic composition and active biochemical functions of a complex microbial community. 26757703 3 112 theme datasets 552:559 arg1 interpretation 528:541 interpretation 528:541 interpretation 528:541 However, the lack of established reference genomes, computational tools and pipelines make analysis and interpretation of these datasets challenging. 26757703 3 112 theme datasets 552:559 arg1 analysis 515:522 analysis 515:522 analysis 515:522 However, the lack of established reference genomes, computational tools and pipelines make analysis and interpretation of these datasets challenging. 26757703 4 113 theme microbiome 733:742 arg1 function 744:751 microbiome function 733:751 microbiome function 733:751 Systematic studies that compare data across microbiomes are needed to demonstrate the ability of such pipelines to deliver biologically meaningful insights on microbiome function. 26757703 6 114 theme low 1181:1183 arg1 complexity 1185:1194 its relatively low complexity 1166:1194 its relatively low complexity 1166:1194 Sequence similarity searches allowed annotation of 19 to 76% of putative messenger RNA (mRNA) reads, with the highest frequency in the kimchi dataset due to its relatively low complexity and availability of closely related reference genomes. 26757703 4 115 theme meaningful 710:719 arg1 insights 721:728 biologically meaningful insights 697:728 biologically meaningful insights on microbiome function 697:751 Systematic studies that compare data across microbiomes are needed to demonstrate the ability of such pipelines to deliver biologically meaningful insights on microbiome function. 27572122 2 0 theme horse 405:409 arg1 EIAVL 427:431 EIAVL 427:431 EIAVL 427:431 In this study, we compare the env gene of the original horse virulent virus (EIAVL) with attenuated strains serially passaged in donkey MDM (EIAVDLV) and donkey dermal cells (EIAVFDDV). 27572122 2 0 theme horse 405:409 arg1 virus 420:424 the original horse virulent virus 392:424 the original horse virulent virus (EIAVL) 392:432 In this study, we compare the env gene of the original horse virulent virus (EIAVL) with attenuated strains serially passaged in donkey MDM (EIAVDLV) and donkey dermal cells (EIAVFDDV). 27572122 0 1 from mutations 11:19 arg1 protein 37:43 the env gp90 protein 24:43 the env gp90 protein that modify N-linked glycosylation of the Chinese EIAV vaccine strain 24:113 Amino acid mutations in the env gp90 protein that modify N-linked glycosylation of the Chinese EIAV vaccine strain enhance resistance to neutralizing antibodies. 27572122 2 2 theme donkey 504:509 arg1 cells 518:522 donkey dermal cells 504:522 donkey dermal cells (EIAVFDDV) 504:533 In this study, we compare the env gene of the original horse virulent virus (EIAVL) with attenuated strains serially passaged in donkey MDM (EIAVDLV) and donkey dermal cells (EIAVFDDV). 27572122 2 2 theme donkey 504:509 arg1 EIAVFDDV 525:532 EIAVFDDV 525:532 EIAVFDDV 525:532 In this study, we compare the env gene of the original horse virulent virus (EIAVL) with attenuated strains serially passaged in donkey MDM (EIAVDLV) and donkey dermal cells (EIAVFDDV). 27572122 5 3 theme donkey 1022:1027 arg1 cells 1036:1040 donkey dermal cells 1022:1040 donkey dermal cells 1022:1040 The resulting virus stocks were characterized for replication efficiency in donkey dermal cells and donkey MDM, and were tested for sensitivity to neutralization using sera from two ponies experimentally infected with EIAVFDDV. 27572122 6 4 theme site-directed 1229:1241 arg1 mutagenesis 1243:1253 site-directed mutagenesis 1229:1253 site-directed mutagenesis 1229:1253 Results clearly show that these mutations generated by site-directed mutagenesis resulted in cloned viruses with enhanced resistance to serum neutralizing antibodies that were also able to recognize parental viruses. 27572122 5 5 theme replication 996:1006 arg1 efficiency 1008:1017 replication efficiency 996:1017 replication efficiency in donkey dermal cells and donkey MDM 996:1055 The resulting virus stocks were characterized for replication efficiency in donkey dermal cells and donkey MDM, and were tested for sensitivity to neutralization using sera from two ponies experimentally infected with EIAVFDDV. 27572122 1 6 theme serial 235:240 arg1 passage 242:248 serial passage 235:248 serial passage of a virulent horse isolate (EIAVL) 235:284 The Chinese EIAV vaccine is an attenuated live virus vaccine obtained by serial passage of a virulent horse isolate (EIAVL) in donkeys (EIAVD) and, subsequently, in donkey cells in vitro. 27572122 0 7 theme N-linked 57:64 arg1 glycosylation 66:78 N-linked glycosylation 57:78 N-linked glycosylation of the Chinese EIAV vaccine strain 57:113 Amino acid mutations in the env gp90 protein that modify N-linked glycosylation of the Chinese EIAV vaccine strain enhance resistance to neutralizing antibodies. 27572122 5 8 from ponies 1128:1133 arg1 sera 1114:1117 sera 1114:1117 sera from two ponies experimentally infected with EIAVFDDV 1114:1171 The resulting virus stocks were characterized for replication efficiency in donkey dermal cells and donkey MDM, and were tested for sensitivity to neutralization using sera from two ponies experimentally infected with EIAVFDDV. 27572122 3 9 theme Genetic 536:542 arg1 comparisons 544:554 Genetic comparisons 536:554 Genetic comparisons among parental and attenuated strains 536:592 Genetic comparisons among parental and attenuated strains found that vaccine strains contained amino acid substitutions/deletions in gp90 that resulted in a loss of three potential N-linked glycosylation sites, designated g5, g9, and g10. 27572122 5 10 theme donkey 1046:1051 arg1 MDM 1053:1055 donkey MDM 1046:1055 donkey MDM 1046:1055 The resulting virus stocks were characterized for replication efficiency in donkey dermal cells and donkey MDM, and were tested for sensitivity to neutralization using sera from two ponies experimentally infected with EIAVFDDV. 27572122 6 11 theme parental 1373:1380 arg1 viruses 1382:1388 parental viruses 1373:1388 parental viruses 1373:1388 Results clearly show that these mutations generated by site-directed mutagenesis resulted in cloned viruses with enhanced resistance to serum neutralizing antibodies that were also able to recognize parental viruses. 27572122 3 12 theme glycosylation 726:738 arg1 sites 740:744 three potential N-linked glycosylation sites 701:744 three potential N-linked glycosylation sites 701:744 Genetic comparisons among parental and attenuated strains found that vaccine strains contained amino acid substitutions/deletions in gp90 that resulted in a loss of three potential N-linked glycosylation sites, designated g5, g9, and g10. 27572122 4 13 theme reverse-mutated 836:850 arg1 viruses 852:858 reverse-mutated viruses 836:858 reverse-mutated viruses 836:858 To investigate the biological significance of these changes, reverse-mutated viruses were constructed in the backbone of the EIAVFDDV infectious molecular clone (pLGFD3). 27572122 3 14 theme amino 631:635 arg1 substitutions/deletions 642:664 amino acid substitutions/deletions 631:664 amino acid substitutions/deletions in gp90 that resulted in a loss of three potential N-linked glycosylation sites, designated g5, g9, and g10 631:772 Genetic comparisons among parental and attenuated strains found that vaccine strains contained amino acid substitutions/deletions in gp90 that resulted in a loss of three potential N-linked glycosylation sites, designated g5, g9, and g10. 27572122 3 15 theme sites 740:744 arg1 loss 693:696 a loss 691:696 a loss of three potential N-linked glycosylation sites, designated g5, g9, and g10 691:772 Genetic comparisons among parental and attenuated strains found that vaccine strains contained amino acid substitutions/deletions in gp90 that resulted in a loss of three potential N-linked glycosylation sites, designated g5, g9, and g10. 27572122 0 16 theme EIAV 95:98 arg1 strain 108:113 the Chinese EIAV vaccine strain 83:113 the Chinese EIAV vaccine strain 83:113 Amino acid mutations in the env gp90 protein that modify N-linked glycosylation of the Chinese EIAV vaccine strain enhance resistance to neutralizing antibodies. 27572122 3 17 theme acid 637:640 arg1 substitutions/deletions 642:664 amino acid substitutions/deletions 631:664 amino acid substitutions/deletions in gp90 that resulted in a loss of three potential N-linked glycosylation sites, designated g5, g9, and g10 631:772 Genetic comparisons among parental and attenuated strains found that vaccine strains contained amino acid substitutions/deletions in gp90 that resulted in a loss of three potential N-linked glycosylation sites, designated g5, g9, and g10. 27572122 3 18 from substitutions/deletions 642:664 arg1 gp90 669:672 gp90 669:672 gp90 669:672 Genetic comparisons among parental and attenuated strains found that vaccine strains contained amino acid substitutions/deletions in gp90 that resulted in a loss of three potential N-linked glycosylation sites, designated g5, g9, and g10. 27572122 7 19 theme vaccine 1489:1495 arg1 strains 1497:1503 the EIAV vaccine strains 1480:1503 the EIAV vaccine strains 1480:1503 This study indicates that these mutations played an important role in the attenuation of the EIAV vaccine strains. 27572122 6 20 theme serum 1310:1314 arg1 antibodies 1329:1338 serum neutralizing antibodies 1310:1338 serum neutralizing antibodies that were also able to recognize parental viruses 1310:1388 Results clearly show that these mutations generated by site-directed mutagenesis resulted in cloned viruses with enhanced resistance to serum neutralizing antibodies that were also able to recognize parental viruses. 27572122 0 21 theme Chinese 87:93 arg1 strain 108:113 the Chinese EIAV vaccine strain 83:113 the Chinese EIAV vaccine strain 83:113 Amino acid mutations in the env gp90 protein that modify N-linked glycosylation of the Chinese EIAV vaccine strain enhance resistance to neutralizing antibodies. 27572122 4 22 theme EIAVFDDV 900:907 arg1 pLGFD3 937:942 pLGFD3 937:942 pLGFD3 937:942 To investigate the biological significance of these changes, reverse-mutated viruses were constructed in the backbone of the EIAVFDDV infectious molecular clone (pLGFD3). 27572122 4 22 theme EIAVFDDV 900:907 arg1 clone 930:934 the EIAVFDDV infectious molecular clone 896:934 the EIAVFDDV infectious molecular clone (pLGFD3) 896:943 To investigate the biological significance of these changes, reverse-mutated viruses were constructed in the backbone of the EIAVFDDV infectious molecular clone (pLGFD3). 27572122 7 23 theme strains 1497:1503 arg1 attenuation 1465:1475 the attenuation 1461:1475 the attenuation of the EIAV vaccine strains 1461:1503 This study indicates that these mutations played an important role in the attenuation of the EIAV vaccine strains. 27572122 0 24 gly glycosylation 66:78 arg1 strain 108:113 the Chinese EIAV vaccine strain 83:113 the Chinese EIAV vaccine strain 83:113 Amino acid mutations in the env gp90 protein that modify N-linked glycosylation of the Chinese EIAV vaccine strain enhance resistance to neutralizing antibodies. 27572122 7 25 theme important 1443:1451 arg1 role 1453:1456 an important role 1440:1456 an important role 1440:1456 This study indicates that these mutations played an important role in the attenuation of the EIAV vaccine strains. 27572122 1 26 theme Chinese 166:172 arg1 vaccine 179:185 The Chinese EIAV vaccine 162:185 The Chinese EIAV vaccine 162:185 The Chinese EIAV vaccine is an attenuated live virus vaccine obtained by serial passage of a virulent horse isolate (EIAVL) in donkeys (EIAVD) and, subsequently, in donkey cells in vitro. 27572122 1 26 theme Chinese 166:172 arg1 vaccine 215:221 an attenuated live virus vaccine 190:221 an attenuated live virus vaccine obtained by serial passage of a virulent horse isolate (EIAVL) 190:284 The Chinese EIAV vaccine is an attenuated live virus vaccine obtained by serial passage of a virulent horse isolate (EIAVL) in donkeys (EIAVD) and, subsequently, in donkey cells in vitro. 27572122 0 27 theme acid 6:9 arg1 mutations 11:19 Amino acid mutations 0:19 Amino acid mutations in the env gp90 protein that modify N-linked glycosylation of the Chinese EIAV vaccine strain 0:113 Amino acid mutations in the env gp90 protein that modify N-linked glycosylation of the Chinese EIAV vaccine strain enhance resistance to neutralizing antibodies. 27572122 2 28 theme original 396:403 arg1 EIAVL 427:431 EIAVL 427:431 EIAVL 427:431 In this study, we compare the env gene of the original horse virulent virus (EIAVL) with attenuated strains serially passaged in donkey MDM (EIAVDLV) and donkey dermal cells (EIAVFDDV). 27572122 2 28 theme original 396:403 arg1 virus 420:424 the original horse virulent virus 392:424 the original horse virulent virus (EIAVL) 392:432 In this study, we compare the env gene of the original horse virulent virus (EIAVL) with attenuated strains serially passaged in donkey MDM (EIAVDLV) and donkey dermal cells (EIAVFDDV). 27572122 1 29 theme EIAV 174:177 arg1 vaccine 179:185 The Chinese EIAV vaccine 162:185 The Chinese EIAV vaccine 162:185 The Chinese EIAV vaccine is an attenuated live virus vaccine obtained by serial passage of a virulent horse isolate (EIAVL) in donkeys (EIAVD) and, subsequently, in donkey cells in vitro. 27572122 1 29 theme EIAV 174:177 arg1 vaccine 215:221 an attenuated live virus vaccine 190:221 an attenuated live virus vaccine obtained by serial passage of a virulent horse isolate (EIAVL) 190:284 The Chinese EIAV vaccine is an attenuated live virus vaccine obtained by serial passage of a virulent horse isolate (EIAVL) in donkeys (EIAVD) and, subsequently, in donkey cells in vitro. 27572122 0 30 theme Amino 0:4 arg1 mutations 11:19 Amino acid mutations 0:19 Amino acid mutations in the env gp90 protein that modify N-linked glycosylation of the Chinese EIAV vaccine strain 0:113 Amino acid mutations in the env gp90 protein that modify N-linked glycosylation of the Chinese EIAV vaccine strain enhance resistance to neutralizing antibodies. 27572122 1 31 theme virulent 255:262 arg1 isolate 270:276 a virulent horse isolate 253:276 a virulent horse isolate (EIAVL) 253:284 The Chinese EIAV vaccine is an attenuated live virus vaccine obtained by serial passage of a virulent horse isolate (EIAVL) in donkeys (EIAVD) and, subsequently, in donkey cells in vitro. 27572122 1 31 theme virulent 255:262 arg1 EIAVL 279:283 EIAVL 279:283 EIAVL 279:283 The Chinese EIAV vaccine is an attenuated live virus vaccine obtained by serial passage of a virulent horse isolate (EIAVL) in donkeys (EIAVD) and, subsequently, in donkey cells in vitro. 27572122 2 32 theme dermal 511:516 arg1 cells 518:522 donkey dermal cells 504:522 donkey dermal cells (EIAVFDDV) 504:533 In this study, we compare the env gene of the original horse virulent virus (EIAVL) with attenuated strains serially passaged in donkey MDM (EIAVDLV) and donkey dermal cells (EIAVFDDV). 27572122 2 32 theme dermal 511:516 arg1 EIAVFDDV 525:532 EIAVFDDV 525:532 EIAVFDDV 525:532 In this study, we compare the env gene of the original horse virulent virus (EIAVL) with attenuated strains serially passaged in donkey MDM (EIAVDLV) and donkey dermal cells (EIAVFDDV). 27572122 4 33 theme clone 930:934 arg1 backbone 884:891 the backbone 880:891 the backbone of the EIAVFDDV infectious molecular clone (pLGFD3) 880:943 To investigate the biological significance of these changes, reverse-mutated viruses were constructed in the backbone of the EIAVFDDV infectious molecular clone (pLGFD3). 27572122 1 34 theme horse 264:268 arg1 isolate 270:276 a virulent horse isolate 253:276 a virulent horse isolate (EIAVL) 253:284 The Chinese EIAV vaccine is an attenuated live virus vaccine obtained by serial passage of a virulent horse isolate (EIAVL) in donkeys (EIAVD) and, subsequently, in donkey cells in vitro. 27572122 1 34 theme horse 264:268 arg1 EIAVL 279:283 EIAVL 279:283 EIAVL 279:283 The Chinese EIAV vaccine is an attenuated live virus vaccine obtained by serial passage of a virulent horse isolate (EIAVL) in donkeys (EIAVD) and, subsequently, in donkey cells in vitro. 27572122 0 35 theme strain 108:113 arg1 glycosylation 66:78 N-linked glycosylation 57:78 N-linked glycosylation of the Chinese EIAV vaccine strain 57:113 Amino acid mutations in the env gp90 protein that modify N-linked glycosylation of the Chinese EIAV vaccine strain enhance resistance to neutralizing antibodies. 27572122 3 36 link N-linked 717:724 arg1 sites 740:744 three potential N-linked glycosylation sites 701:744 three potential N-linked glycosylation sites 701:744 Genetic comparisons among parental and attenuated strains found that vaccine strains contained amino acid substitutions/deletions in gp90 that resulted in a loss of three potential N-linked glycosylation sites, designated g5, g9, and g10. 27572122 5 37 from efficiency 1008:1017 arg1 cells 1036:1040 donkey dermal cells 1022:1040 donkey dermal cells 1022:1040 The resulting virus stocks were characterized for replication efficiency in donkey dermal cells and donkey MDM, and were tested for sensitivity to neutralization using sera from two ponies experimentally infected with EIAVFDDV. 27572122 5 37 from efficiency 1008:1017 arg1 MDM 1053:1055 donkey MDM 1046:1055 donkey MDM 1046:1055 The resulting virus stocks were characterized for replication efficiency in donkey dermal cells and donkey MDM, and were tested for sensitivity to neutralization using sera from two ponies experimentally infected with EIAVFDDV. 27572122 1 38 theme isolate 270:276 arg1 passage 242:248 serial passage 235:248 serial passage of a virulent horse isolate (EIAVL) 235:284 The Chinese EIAV vaccine is an attenuated live virus vaccine obtained by serial passage of a virulent horse isolate (EIAVL) in donkeys (EIAVD) and, subsequently, in donkey cells in vitro. 27572122 0 39 theme vaccine 100:106 arg1 strain 108:113 the Chinese EIAV vaccine strain 83:113 the Chinese EIAV vaccine strain 83:113 Amino acid mutations in the env gp90 protein that modify N-linked glycosylation of the Chinese EIAV vaccine strain enhance resistance to neutralizing antibodies. 27572122 1 40 theme donkey 327:332 arg1 cells 334:338 donkey cells 327:338 donkey cells 327:338 The Chinese EIAV vaccine is an attenuated live virus vaccine obtained by serial passage of a virulent horse isolate (EIAVL) in donkeys (EIAVD) and, subsequently, in donkey cells in vitro. 27572122 0 41 theme env 28:30 arg1 protein 37:43 the env gp90 protein 24:43 the env gp90 protein that modify N-linked glycosylation of the Chinese EIAV vaccine strain 24:113 Amino acid mutations in the env gp90 protein that modify N-linked glycosylation of the Chinese EIAV vaccine strain enhance resistance to neutralizing antibodies. 27572122 4 42 theme changes 827:833 arg1 significance 805:816 the biological significance 790:816 the biological significance of these changes 790:833 To investigate the biological significance of these changes, reverse-mutated viruses were constructed in the backbone of the EIAVFDDV infectious molecular clone (pLGFD3). 27572122 1 43 theme attenuated 193:202 arg1 vaccine 179:185 The Chinese EIAV vaccine 162:185 The Chinese EIAV vaccine 162:185 The Chinese EIAV vaccine is an attenuated live virus vaccine obtained by serial passage of a virulent horse isolate (EIAVL) in donkeys (EIAVD) and, subsequently, in donkey cells in vitro. 27572122 1 43 theme attenuated 193:202 arg1 vaccine 215:221 an attenuated live virus vaccine 190:221 an attenuated live virus vaccine obtained by serial passage of a virulent horse isolate (EIAVL) 190:284 The Chinese EIAV vaccine is an attenuated live virus vaccine obtained by serial passage of a virulent horse isolate (EIAVL) in donkeys (EIAVD) and, subsequently, in donkey cells in vitro. 27572122 4 44 theme infectious 909:918 arg1 pLGFD3 937:942 pLGFD3 937:942 pLGFD3 937:942 To investigate the biological significance of these changes, reverse-mutated viruses were constructed in the backbone of the EIAVFDDV infectious molecular clone (pLGFD3). 27572122 4 44 theme infectious 909:918 arg1 clone 930:934 the EIAVFDDV infectious molecular clone 896:934 the EIAVFDDV infectious molecular clone (pLGFD3) 896:943 To investigate the biological significance of these changes, reverse-mutated viruses were constructed in the backbone of the EIAVFDDV infectious molecular clone (pLGFD3). 27572122 2 45 theme attenuated 439:448 arg1 strains 450:456 attenuated strains 439:456 attenuated strains serially passaged in donkey MDM (EIAVDLV) and donkey dermal cells (EIAVFDDV) 439:533 In this study, we compare the env gene of the original horse virulent virus (EIAVL) with attenuated strains serially passaged in donkey MDM (EIAVDLV) and donkey dermal cells (EIAVFDDV). 27572122 1 46 theme live 204:207 arg1 vaccine 179:185 The Chinese EIAV vaccine 162:185 The Chinese EIAV vaccine 162:185 The Chinese EIAV vaccine is an attenuated live virus vaccine obtained by serial passage of a virulent horse isolate (EIAVL) in donkeys (EIAVD) and, subsequently, in donkey cells in vitro. 27572122 1 46 theme live 204:207 arg1 vaccine 215:221 an attenuated live virus vaccine 190:221 an attenuated live virus vaccine obtained by serial passage of a virulent horse isolate (EIAVL) 190:284 The Chinese EIAV vaccine is an attenuated live virus vaccine obtained by serial passage of a virulent horse isolate (EIAVL) in donkeys (EIAVD) and, subsequently, in donkey cells in vitro. 27572122 4 47 theme molecular 920:928 arg1 pLGFD3 937:942 pLGFD3 937:942 pLGFD3 937:942 To investigate the biological significance of these changes, reverse-mutated viruses were constructed in the backbone of the EIAVFDDV infectious molecular clone (pLGFD3). 27572122 4 47 theme molecular 920:928 arg1 clone 930:934 the EIAVFDDV infectious molecular clone 896:934 the EIAVFDDV infectious molecular clone (pLGFD3) 896:943 To investigate the biological significance of these changes, reverse-mutated viruses were constructed in the backbone of the EIAVFDDV infectious molecular clone (pLGFD3). 27572122 0 48 theme neutralizing 137:148 arg1 antibodies 150:159 neutralizing antibodies 137:159 neutralizing antibodies 137:159 Amino acid mutations in the env gp90 protein that modify N-linked glycosylation of the Chinese EIAV vaccine strain enhance resistance to neutralizing antibodies. 27572122 3 49 gly glycosylation 726:738 arg2 sites 740:744 three potential N-linked glycosylation sites 701:744 three potential N-linked glycosylation sites 701:744 Genetic comparisons among parental and attenuated strains found that vaccine strains contained amino acid substitutions/deletions in gp90 that resulted in a loss of three potential N-linked glycosylation sites, designated g5, g9, and g10. 27572122 3 49 gly glycosylation 726:738 arg2 three 701:705 three 701:705 three 701:705 Genetic comparisons among parental and attenuated strains found that vaccine strains contained amino acid substitutions/deletions in gp90 that resulted in a loss of three potential N-linked glycosylation sites, designated g5, g9, and g10. 27572122 0 50 link N-linked 57:64 arg1 glycosylation 66:78 N-linked glycosylation 57:78 N-linked glycosylation of the Chinese EIAV vaccine strain 57:113 Amino acid mutations in the env gp90 protein that modify N-linked glycosylation of the Chinese EIAV vaccine strain enhance resistance to neutralizing antibodies. 27572122 3 51 contain contained 621:629 arg2 substitutions/deletions 642:664 amino acid substitutions/deletions 631:664 amino acid substitutions/deletions in gp90 that resulted in a loss of three potential N-linked glycosylation sites, designated g5, g9, and g10 631:772 Genetic comparisons among parental and attenuated strains found that vaccine strains contained amino acid substitutions/deletions in gp90 that resulted in a loss of three potential N-linked glycosylation sites, designated g5, g9, and g10. 27572122 3 51 contain contained 621:629 arg1 strains 613:619 vaccine strains 605:619 vaccine strains 605:619 Genetic comparisons among parental and attenuated strains found that vaccine strains contained amino acid substitutions/deletions in gp90 that resulted in a loss of three potential N-linked glycosylation sites, designated g5, g9, and g10. 27572122 0 52 theme gp90 32:35 arg1 protein 37:43 the env gp90 protein 24:43 the env gp90 protein that modify N-linked glycosylation of the Chinese EIAV vaccine strain 24:113 Amino acid mutations in the env gp90 protein that modify N-linked glycosylation of the Chinese EIAV vaccine strain enhance resistance to neutralizing antibodies. 27572122 6 53 theme cloned 1267:1272 arg1 viruses 1274:1280 cloned viruses 1267:1280 cloned viruses with enhanced resistance to serum neutralizing antibodies that were also able to recognize parental viruses 1267:1388 Results clearly show that these mutations generated by site-directed mutagenesis resulted in cloned viruses with enhanced resistance to serum neutralizing antibodies that were also able to recognize parental viruses. 27572122 2 54 theme env 380:382 arg1 gene 384:387 the env gene 376:387 the env gene of the original horse virulent virus (EIAVL) 376:432 In this study, we compare the env gene of the original horse virulent virus (EIAVL) with attenuated strains serially passaged in donkey MDM (EIAVDLV) and donkey dermal cells (EIAVFDDV). 27572122 2 55 theme donkey 479:484 arg1 EIAVDLV 491:497 EIAVDLV 491:497 EIAVDLV 491:497 In this study, we compare the env gene of the original horse virulent virus (EIAVL) with attenuated strains serially passaged in donkey MDM (EIAVDLV) and donkey dermal cells (EIAVFDDV). 27572122 2 55 theme donkey 479:484 arg1 MDM 486:488 donkey MDM 479:488 donkey MDM (EIAVDLV) 479:498 In this study, we compare the env gene of the original horse virulent virus (EIAVL) with attenuated strains serially passaged in donkey MDM (EIAVDLV) and donkey dermal cells (EIAVFDDV). 27572122 3 56 theme attenuated 575:584 arg1 strains 586:592 attenuated strains 575:592 attenuated strains 575:592 Genetic comparisons among parental and attenuated strains found that vaccine strains contained amino acid substitutions/deletions in gp90 that resulted in a loss of three potential N-linked glycosylation sites, designated g5, g9, and g10. 27572122 1 57 theme virus 209:213 arg1 vaccine 179:185 The Chinese EIAV vaccine 162:185 The Chinese EIAV vaccine 162:185 The Chinese EIAV vaccine is an attenuated live virus vaccine obtained by serial passage of a virulent horse isolate (EIAVL) in donkeys (EIAVD) and, subsequently, in donkey cells in vitro. 27572122 1 57 theme virus 209:213 arg1 vaccine 215:221 an attenuated live virus vaccine 190:221 an attenuated live virus vaccine obtained by serial passage of a virulent horse isolate (EIAVL) 190:284 The Chinese EIAV vaccine is an attenuated live virus vaccine obtained by serial passage of a virulent horse isolate (EIAVL) in donkeys (EIAVD) and, subsequently, in donkey cells in vitro. 27572122 4 58 theme biological 794:803 arg1 significance 805:816 the biological significance 790:816 the biological significance of these changes 790:833 To investigate the biological significance of these changes, reverse-mutated viruses were constructed in the backbone of the EIAVFDDV infectious molecular clone (pLGFD3). 27572122 5 59 theme resulting 950:958 arg1 stocks 966:971 The resulting virus stocks 946:971 The resulting virus stocks 946:971 The resulting virus stocks were characterized for replication efficiency in donkey dermal cells and donkey MDM, and were tested for sensitivity to neutralization using sera from two ponies experimentally infected with EIAVFDDV. 27572122 7 60 theme EIAV 1484:1487 arg1 strains 1497:1503 the EIAV vaccine strains 1480:1503 the EIAV vaccine strains 1480:1503 This study indicates that these mutations played an important role in the attenuation of the EIAV vaccine strains. 27572122 3 61 theme N-linked 717:724 arg1 sites 740:744 three potential N-linked glycosylation sites 701:744 three potential N-linked glycosylation sites 701:744 Genetic comparisons among parental and attenuated strains found that vaccine strains contained amino acid substitutions/deletions in gp90 that resulted in a loss of three potential N-linked glycosylation sites, designated g5, g9, and g10. 27572122 2 62 theme virus 420:424 arg1 gene 384:387 the env gene 376:387 the env gene of the original horse virulent virus (EIAVL) 376:432 In this study, we compare the env gene of the original horse virulent virus (EIAVL) with attenuated strains serially passaged in donkey MDM (EIAVDLV) and donkey dermal cells (EIAVFDDV). 27572122 5 63 theme virus 960:964 arg1 stocks 966:971 The resulting virus stocks 946:971 The resulting virus stocks 946:971 The resulting virus stocks were characterized for replication efficiency in donkey dermal cells and donkey MDM, and were tested for sensitivity to neutralization using sera from two ponies experimentally infected with EIAVFDDV. 27572122 6 64 theme neutralizing 1316:1327 arg1 antibodies 1329:1338 serum neutralizing antibodies 1310:1338 serum neutralizing antibodies that were also able to recognize parental viruses 1310:1388 Results clearly show that these mutations generated by site-directed mutagenesis resulted in cloned viruses with enhanced resistance to serum neutralizing antibodies that were also able to recognize parental viruses. 27572122 6 65 with viruses 1274:1280 arg1 resistance 1296:1305 enhanced resistance 1287:1305 enhanced resistance to serum neutralizing antibodies that were also able to recognize parental viruses 1287:1388 Results clearly show that these mutations generated by site-directed mutagenesis resulted in cloned viruses with enhanced resistance to serum neutralizing antibodies that were also able to recognize parental viruses. 27572122 2 66 theme virulent 411:418 arg1 EIAVL 427:431 EIAVL 427:431 EIAVL 427:431 In this study, we compare the env gene of the original horse virulent virus (EIAVL) with attenuated strains serially passaged in donkey MDM (EIAVDLV) and donkey dermal cells (EIAVFDDV). 27572122 2 66 theme virulent 411:418 arg1 virus 420:424 the original horse virulent virus 392:424 the original horse virulent virus (EIAVL) 392:432 In this study, we compare the env gene of the original horse virulent virus (EIAVL) with attenuated strains serially passaged in donkey MDM (EIAVDLV) and donkey dermal cells (EIAVFDDV). 27572122 5 67 theme dermal 1029:1034 arg1 cells 1036:1040 donkey dermal cells 1022:1040 donkey dermal cells 1022:1040 The resulting virus stocks were characterized for replication efficiency in donkey dermal cells and donkey MDM, and were tested for sensitivity to neutralization using sera from two ponies experimentally infected with EIAVFDDV. 27572122 3 68 theme vaccine 605:611 arg1 strains 613:619 vaccine strains 605:619 vaccine strains 605:619 Genetic comparisons among parental and attenuated strains found that vaccine strains contained amino acid substitutions/deletions in gp90 that resulted in a loss of three potential N-linked glycosylation sites, designated g5, g9, and g10. 27572122 3 69 theme potential 707:715 arg1 sites 740:744 three potential N-linked glycosylation sites 701:744 three potential N-linked glycosylation sites 701:744 Genetic comparisons among parental and attenuated strains found that vaccine strains contained amino acid substitutions/deletions in gp90 that resulted in a loss of three potential N-linked glycosylation sites, designated g5, g9, and g10. 27572122 6 70 theme enhanced 1287:1294 arg1 resistance 1296:1305 enhanced resistance 1287:1305 enhanced resistance to serum neutralizing antibodies that were also able to recognize parental viruses 1287:1388 Results clearly show that these mutations generated by site-directed mutagenesis resulted in cloned viruses with enhanced resistance to serum neutralizing antibodies that were also able to recognize parental viruses. 26769631 7 0 theme trafficking 1304:1314 arg1 efficiency 1274:1283 the efficiency 1270:1283 the efficiency of HaF folding and trafficking 1270:1314 In general, the conserved site N526 was critical to the functioning of HaF, as absence of N-glycosylation of N526 reduced the efficiency of HaF folding and trafficking, consequently decreased fusogenicity and modified the subcellular localization of HaF proteins, and thus impaired virus production and infectivity. 26769631 6 1 gly N-glycosylated 1057:1070 arg1 four 955:958 four 955:958 four 955:958 The results showed that four of these five potential glycosylation sites in the F(1) subunit, N293, N361, N526 and N571, were N-glycosylated in F proteins of mature HearNPV budded viruses (BVs) but that N595 was not. 26769631 6 1 gly N-glycosylated 1057:1070 arg1 N526 1037:1040 N526 1037:1040 N526 1037:1040 The results showed that four of these five potential glycosylation sites in the F(1) subunit, N293, N361, N526 and N571, were N-glycosylated in F proteins of mature HearNPV budded viruses (BVs) but that N595 was not. 26769631 6 1 gly N-glycosylated 1057:1070 arg2 sites 998:1002 these five potential glycosylation sites 963:1002 these five potential glycosylation sites in the F(1) subunit 963:1022 The results showed that four of these five potential glycosylation sites in the F(1) subunit, N293, N361, N526 and N571, were N-glycosylated in F proteins of mature HearNPV budded viruses (BVs) but that N595 was not. 26769631 6 1 gly N-glycosylated 1057:1070 arg1 N571 1046:1049 N571 1046:1049 N571 1046:1049 The results showed that four of these five potential glycosylation sites in the F(1) subunit, N293, N361, N526 and N571, were N-glycosylated in F proteins of mature HearNPV budded viruses (BVs) but that N595 was not. 26769631 6 1 gly N-glycosylated 1057:1070 arg1 proteins 1077:1084 F proteins 1075:1084 F proteins of mature HearNPV budded viruses (BVs) 1075:1123 The results showed that four of these five potential glycosylation sites in the F(1) subunit, N293, N361, N526 and N571, were N-glycosylated in F proteins of mature HearNPV budded viruses (BVs) but that N595 was not. 26769631 6 1 gly N-glycosylated 1057:1070 arg2 N361 1031:1034 N361 1031:1034 N361 1031:1034 The results showed that four of these five potential glycosylation sites in the F(1) subunit, N293, N361, N526 and N571, were N-glycosylated in F proteins of mature HearNPV budded viruses (BVs) but that N595 was not. 26769631 6 1 gly N-glycosylated 1057:1070 arg2 N526 1037:1040 N526 1037:1040 N526 1037:1040 The results showed that four of these five potential glycosylation sites in the F(1) subunit, N293, N361, N526 and N571, were N-glycosylated in F proteins of mature HearNPV budded viruses (BVs) but that N595 was not. 26769631 6 1 gly N-glycosylated 1057:1070 arg2 four 955:958 four 955:958 four 955:958 The results showed that four of these five potential glycosylation sites in the F(1) subunit, N293, N361, N526 and N571, were N-glycosylated in F proteins of mature HearNPV budded viruses (BVs) but that N595 was not. 26769631 6 1 gly N-glycosylated 1057:1070 arg1 N361 1031:1034 N361 1031:1034 N361 1031:1034 The results showed that four of these five potential glycosylation sites in the F(1) subunit, N293, N361, N526 and N571, were N-glycosylated in F proteins of mature HearNPV budded viruses (BVs) but that N595 was not. 26769631 6 1 gly N-glycosylated 1057:1070 arg2 N571 1046:1049 N571 1046:1049 N571 1046:1049 The results showed that four of these five potential glycosylation sites in the F(1) subunit, N293, N361, N526 and N571, were N-glycosylated in F proteins of mature HearNPV budded viruses (BVs) but that N595 was not. 26769631 6 1 gly N-glycosylated 1057:1070 arg1 sites 998:1002 these five potential glycosylation sites 963:1002 these five potential glycosylation sites in the F(1) subunit 963:1022 The results showed that four of these five potential glycosylation sites in the F(1) subunit, N293, N361, N526 and N571, were N-glycosylated in F proteins of mature HearNPV budded viruses (BVs) but that N595 was not. 26769631 2 2 theme envelope 358:365 arg1 folding 380:386 virus envelope glycoprotein folding 352:386 virus envelope glycoprotein folding 352:386 N-Linked glycosylation of virus envelope glycoprotein is important for virus envelope glycoprotein folding and its function in general. 26769631 7 3 theme folding 1292:1298 arg1 efficiency 1274:1283 the efficiency 1270:1283 the efficiency of HaF folding and trafficking 1270:1314 In general, the conserved site N526 was critical to the functioning of HaF, as absence of N-glycosylation of N526 reduced the efficiency of HaF folding and trafficking, consequently decreased fusogenicity and modified the subcellular localization of HaF proteins, and thus impaired virus production and infectivity. 26769631 2 4 gly glycosylation 290:302 arg1 glycoprotein 367:378 virus envelope glycoprotein folding 352:386 virus envelope glycoprotein folding 352:386 N-Linked glycosylation of virus envelope glycoprotein is important for virus envelope glycoprotein folding and its function in general. 26769631 2 4 gly glycosylation 290:302 arg1 virus 352:356 virus envelope glycoprotein folding 352:386 virus envelope glycoprotein folding 352:386 N-Linked glycosylation of virus envelope glycoprotein is important for virus envelope glycoprotein folding and its function in general. 26769631 2 4 gly glycosylation 290:302 arg1 envelope 358:365 virus envelope glycoprotein folding 352:386 virus envelope glycoprotein folding 352:386 N-Linked glycosylation of virus envelope glycoprotein is important for virus envelope glycoprotein folding and its function in general. 26769631 2 4 gly glycosylation 290:302 arg1 glycoprotein 322:333 virus envelope glycoprotein 307:333 virus envelope glycoprotein 307:333 N-Linked glycosylation of virus envelope glycoprotein is important for virus envelope glycoprotein folding and its function in general. 26769631 6 5 from sites 998:1002 arg1 subunit 1016:1022 the F(1) subunit 1007:1022 the F(1) subunit 1007:1022 The results showed that four of these five potential glycosylation sites in the F(1) subunit, N293, N361, N526 and N571, were N-glycosylated in F proteins of mature HearNPV budded viruses (BVs) but that N595 was not. 26769631 2 6 theme N-Linked 281:288 arg1 glycosylation 290:302 N-Linked glycosylation 281:302 N-Linked glycosylation of virus envelope glycoprotein 281:333 N-Linked glycosylation of virus envelope glycoprotein is important for virus envelope glycoprotein folding and its function in general. 26769631 8 7 theme different 1539:1547 arg1 effects 1549:1555 different effects 1539:1555 different effects 1539:1555 The absence of N-glycosylation at other individual sites was found to have different effects on the fusogenicity and subcelluar distribution of HaF proteins in HzAM1 cells. 26769631 1 8 theme infection 264:272 arg1 cycle 274:278 the virus infection cycle 254:278 the virus infection cycle 254:278 The envelope fusion (F) protein of baculoviruses is a heavily N-glycosylated protein that plays a significant role in the virus infection cycle. 26769631 1 9 theme baculoviruses 171:183 arg1 protein 213:219 a heavily N-glycosylated protein 188:219 a heavily N-glycosylated protein that plays a significant role in the virus infection cycle 188:278 The envelope fusion (F) protein of baculoviruses is a heavily N-glycosylated protein that plays a significant role in the virus infection cycle. 26769631 1 9 theme baculoviruses 171:183 arg1 protein 160:166 The envelope fusion (F) protein 136:166 The envelope fusion (F) protein of baculoviruses 136:183 The envelope fusion (F) protein of baculoviruses is a heavily N-glycosylated protein that plays a significant role in the virus infection cycle. 26769631 6 10 theme budded 1104:1109 arg1 BVs 1120:1122 BVs 1120:1122 BVs 1120:1122 The results showed that four of these five potential glycosylation sites in the F(1) subunit, N293, N361, N526 and N571, were N-glycosylated in F proteins of mature HearNPV budded viruses (BVs) but that N595 was not. 26769631 6 10 theme budded 1104:1109 arg1 viruses 1111:1117 mature HearNPV budded viruses 1089:1117 mature HearNPV budded viruses (BVs) 1089:1123 The results showed that four of these five potential glycosylation sites in the F(1) subunit, N293, N361, N526 and N571, were N-glycosylated in F proteins of mature HearNPV budded viruses (BVs) but that N595 was not. 26769631 2 11 theme envelope 313:320 arg1 glycoprotein 322:333 virus envelope glycoprotein 307:333 virus envelope glycoprotein 307:333 N-Linked glycosylation of virus envelope glycoprotein is important for virus envelope glycoprotein folding and its function in general. 26769631 2 12 from folding 380:386 arg1 general 408:414 general 408:414 general 408:414 N-Linked glycosylation of virus envelope glycoprotein is important for virus envelope glycoprotein folding and its function in general. 26769631 4 13 theme HaF 605:607 arg1 N104 596:599 N104 596:599 N104 596:599 The N-glycosylation site located in the F(2) subunit (N104) of HaF has been identified and functionally characterized previously (Long et al., 2007). 26769631 4 13 theme HaF 605:607 arg1 subunit 587:593 the F(2) subunit 578:593 the F(2) subunit (N104) of HaF 578:607 The N-glycosylation site located in the F(2) subunit (N104) of HaF has been identified and functionally characterized previously (Long et al., 2007). 26769631 3 14 theme nucleopolyhedrovirus 510:529 arg1 protein 478:484 the F (HaF) protein 466:484 the F (HaF) protein of Helicoverpa armigera nucleopolyhedrovirus (HearNPV) 466:539 There are six predicted N-glycosylation sites in the F (HaF) protein of Helicoverpa armigera nucleopolyhedrovirus (HearNPV). 26769631 8 15 theme subcelluar 1581:1590 arg1 distribution 1592:1603 subcelluar distribution 1581:1603 subcelluar distribution 1581:1603 The absence of N-glycosylation at other individual sites was found to have different effects on the fusogenicity and subcelluar distribution of HaF proteins in HzAM1 cells. 26769631 1 16 theme N-glycosylated 198:211 arg1 protein 213:219 a heavily N-glycosylated protein 188:219 a heavily N-glycosylated protein that plays a significant role in the virus infection cycle 188:278 The envelope fusion (F) protein of baculoviruses is a heavily N-glycosylated protein that plays a significant role in the virus infection cycle. 26769631 1 16 theme N-glycosylated 198:211 arg1 protein 160:166 The envelope fusion (F) protein 136:166 The envelope fusion (F) protein of baculoviruses 136:183 The envelope fusion (F) protein of baculoviruses is a heavily N-glycosylated protein that plays a significant role in the virus infection cycle. 26769631 6 17 theme HearNPV 1096:1102 arg1 BVs 1120:1122 BVs 1120:1122 BVs 1120:1122 The results showed that four of these five potential glycosylation sites in the F(1) subunit, N293, N361, N526 and N571, were N-glycosylated in F proteins of mature HearNPV budded viruses (BVs) but that N595 was not. 26769631 6 17 theme HearNPV 1096:1102 arg1 viruses 1111:1117 mature HearNPV budded viruses 1089:1117 mature HearNPV budded viruses (BVs) 1089:1123 The results showed that four of these five potential glycosylation sites in the F(1) subunit, N293, N361, N526 and N571, were N-glycosylated in F proteins of mature HearNPV budded viruses (BVs) but that N595 was not. 26769631 5 18 theme HaF1 769:772 arg1 subunit 774:780 the HaF1 subunit 765:780 the HaF1 subunit 765:780 In this study, the other five potential N-glycosylation sites located in the HaF1 subunit, namely, N293, N361, N526, N571 and N595, were analysed extensively to examine their N-glycosylation and relative importance to the function of HaF. 26769631 8 19 theme proteins 1612:1619 arg1 fusogenicity 1564:1575 fusogenicity 1564:1575 fusogenicity 1564:1575 The absence of N-glycosylation at other individual sites was found to have different effects on the fusogenicity and subcelluar distribution of HaF proteins in HzAM1 cells. 26769631 8 19 theme proteins 1612:1619 arg1 distribution 1592:1603 subcelluar distribution 1581:1603 subcelluar distribution 1581:1603 The absence of N-glycosylation at other individual sites was found to have different effects on the fusogenicity and subcelluar distribution of HaF proteins in HzAM1 cells. 26769631 6 20 theme F 1075:1075 arg1 proteins 1077:1084 F proteins 1075:1084 F proteins of mature HearNPV budded viruses (BVs) 1075:1123 The results showed that four of these five potential glycosylation sites in the F(1) subunit, N293, N361, N526 and N571, were N-glycosylated in F proteins of mature HearNPV budded viruses (BVs) but that N595 was not. 26769631 6 21 from proteins 1077:1084 arg1 N-glycosylated 1057:1070 N-glycosylated 1057:1070 N-glycosylated 1057:1070 The results showed that four of these five potential glycosylation sites in the F(1) subunit, N293, N361, N526 and N571, were N-glycosylated in F proteins of mature HearNPV budded viruses (BVs) but that N595 was not. 26769631 8 22 theme HzAM1 1624:1628 arg1 cells 1630:1634 HzAM1 cells 1624:1634 HzAM1 cells 1624:1634 The absence of N-glycosylation at other individual sites was found to have different effects on the fusogenicity and subcelluar distribution of HaF proteins in HzAM1 cells. 26769631 1 23 theme fusion 149:154 arg1 protein 213:219 a heavily N-glycosylated protein 188:219 a heavily N-glycosylated protein that plays a significant role in the virus infection cycle 188:278 The envelope fusion (F) protein of baculoviruses is a heavily N-glycosylated protein that plays a significant role in the virus infection cycle. 26769631 1 23 theme fusion 149:154 arg1 protein 160:166 The envelope fusion (F) protein 136:166 The envelope fusion (F) protein of baculoviruses 136:183 The envelope fusion (F) protein of baculoviruses is a heavily N-glycosylated protein that plays a significant role in the virus infection cycle. 26769631 7 24 theme site 1174:1177 arg1 critical 1188:1195 critical 1188:1195 critical 1188:1195 In general, the conserved site N526 was critical to the functioning of HaF, as absence of N-glycosylation of N526 reduced the efficiency of HaF folding and trafficking, consequently decreased fusogenicity and modified the subcellular localization of HaF proteins, and thus impaired virus production and infectivity. 26769631 7 24 theme site 1174:1177 arg1 N526 1179:1182 the conserved site N526 1160:1182 the conserved site N526 1160:1182 In general, the conserved site N526 was critical to the functioning of HaF, as absence of N-glycosylation of N526 reduced the efficiency of HaF folding and trafficking, consequently decreased fusogenicity and modified the subcellular localization of HaF proteins, and thus impaired virus production and infectivity. 26769631 0 25 theme envelope 64:71 arg1 F 88:88 envelope fusion protein F 64:88 envelope fusion protein F of Helicoverpa armigera nucleopolyhedrovirus 64:133 Mutational and functional analysis of N-linked glycosylation of envelope fusion protein F of Helicoverpa armigera nucleopolyhedrovirus. 26769631 1 26 theme F 157:157 arg1 protein 213:219 a heavily N-glycosylated protein 188:219 a heavily N-glycosylated protein that plays a significant role in the virus infection cycle 188:278 The envelope fusion (F) protein of baculoviruses is a heavily N-glycosylated protein that plays a significant role in the virus infection cycle. 26769631 1 26 theme F 157:157 arg1 protein 160:166 The envelope fusion (F) protein 136:166 The envelope fusion (F) protein of baculoviruses 136:183 The envelope fusion (F) protein of baculoviruses is a heavily N-glycosylated protein that plays a significant role in the virus infection cycle. 26769631 0 27 theme protein 80:86 arg1 F 88:88 envelope fusion protein F 64:88 envelope fusion protein F of Helicoverpa armigera nucleopolyhedrovirus 64:133 Mutational and functional analysis of N-linked glycosylation of envelope fusion protein F of Helicoverpa armigera nucleopolyhedrovirus. 26769631 7 28 theme proteins 1402:1409 arg1 localization 1382:1393 the subcellular localization 1366:1393 the subcellular localization of HaF proteins 1366:1409 In general, the conserved site N526 was critical to the functioning of HaF, as absence of N-glycosylation of N526 reduced the efficiency of HaF folding and trafficking, consequently decreased fusogenicity and modified the subcellular localization of HaF proteins, and thus impaired virus production and infectivity. 26769631 5 29 theme relative 887:894 arg1 importance 896:905 relative importance 887:905 relative importance 887:905 In this study, the other five potential N-glycosylation sites located in the HaF1 subunit, namely, N293, N361, N526, N571 and N595, were analysed extensively to examine their N-glycosylation and relative importance to the function of HaF. 26769631 0 30 theme armigera 105:112 arg1 nucleopolyhedrovirus 114:133 Helicoverpa armigera nucleopolyhedrovirus 93:133 Helicoverpa armigera nucleopolyhedrovirus 93:133 Mutational and functional analysis of N-linked glycosylation of envelope fusion protein F of Helicoverpa armigera nucleopolyhedrovirus. 26769631 8 31 contain have 1534:1537 arg1 absence 1468:1474 The absence 1464:1474 The absence of N-glycosylation at other individual sites 1464:1519 The absence of N-glycosylation at other individual sites was found to have different effects on the fusogenicity and subcelluar distribution of HaF proteins in HzAM1 cells. 26769631 8 31 contain have 1534:1537 arg2 effects 1549:1555 different effects 1539:1555 different effects 1539:1555 The absence of N-glycosylation at other individual sites was found to have different effects on the fusogenicity and subcelluar distribution of HaF proteins in HzAM1 cells. 26769631 0 32 theme N-linked 38:45 arg1 glycosylation 47:59 N-linked glycosylation 38:59 N-linked glycosylation of envelope fusion protein F of Helicoverpa armigera nucleopolyhedrovirus 38:133 Mutational and functional analysis of N-linked glycosylation of envelope fusion protein F of Helicoverpa armigera nucleopolyhedrovirus. 26769631 7 33 theme conserved 1164:1172 arg1 critical 1188:1195 critical 1188:1195 critical 1188:1195 In general, the conserved site N526 was critical to the functioning of HaF, as absence of N-glycosylation of N526 reduced the efficiency of HaF folding and trafficking, consequently decreased fusogenicity and modified the subcellular localization of HaF proteins, and thus impaired virus production and infectivity. 26769631 7 33 theme conserved 1164:1172 arg1 N526 1179:1182 the conserved site N526 1160:1182 the conserved site N526 1160:1182 In general, the conserved site N526 was critical to the functioning of HaF, as absence of N-glycosylation of N526 reduced the efficiency of HaF folding and trafficking, consequently decreased fusogenicity and modified the subcellular localization of HaF proteins, and thus impaired virus production and infectivity. 26769631 3 34 theme predicted 431:439 arg1 sites 457:461 six predicted N-glycosylation sites 427:461 six predicted N-glycosylation sites in the F (HaF) protein of Helicoverpa armigera nucleopolyhedrovirus (HearNPV) 427:539 There are six predicted N-glycosylation sites in the F (HaF) protein of Helicoverpa armigera nucleopolyhedrovirus (HearNPV). 26769631 0 35 theme Mutational 0:9 arg1 analysis 26:33 Mutational and functional analysis 0:33 analysis 26:33 Mutational and functional analysis of N-linked glycosylation of envelope fusion protein F of Helicoverpa armigera nucleopolyhedrovirus. 26769631 0 36 theme functional 15:24 arg1 analysis 26:33 Mutational and functional analysis 0:33 analysis 26:33 Mutational and functional analysis of N-linked glycosylation of envelope fusion protein F of Helicoverpa armigera nucleopolyhedrovirus. 26769631 5 37 theme N-glycosylation 732:746 arg1 sites 748:752 the other five potential N-glycosylation sites 707:752 the other five potential N-glycosylation sites located in the HaF1 subunit, namely 707:788 In this study, the other five potential N-glycosylation sites located in the HaF1 subunit, namely, N293, N361, N526, N571 and N595, were analysed extensively to examine their N-glycosylation and relative importance to the function of HaF. 26769631 5 37 theme N-glycosylation 732:746 arg1 N361 797:800 N361 797:800 N361 797:800 In this study, the other five potential N-glycosylation sites located in the HaF1 subunit, namely, N293, N361, N526, N571 and N595, were analysed extensively to examine their N-glycosylation and relative importance to the function of HaF. 26769631 5 37 theme N-glycosylation 732:746 arg1 N595 818:821 N595 818:821 N595 818:821 In this study, the other five potential N-glycosylation sites located in the HaF1 subunit, namely, N293, N361, N526, N571 and N595, were analysed extensively to examine their N-glycosylation and relative importance to the function of HaF. 26769631 5 37 theme N-glycosylation 732:746 arg1 N571 809:812 N571 809:812 N571 809:812 In this study, the other five potential N-glycosylation sites located in the HaF1 subunit, namely, N293, N361, N526, N571 and N595, were analysed extensively to examine their N-glycosylation and relative importance to the function of HaF. 26769631 5 37 theme N-glycosylation 732:746 arg1 N526 803:806 N526 803:806 N526 803:806 In this study, the other five potential N-glycosylation sites located in the HaF1 subunit, namely, N293, N361, N526, N571 and N595, were analysed extensively to examine their N-glycosylation and relative importance to the function of HaF. 26769631 2 38 from function 396:403 arg1 general 408:414 general 408:414 general 408:414 N-Linked glycosylation of virus envelope glycoprotein is important for virus envelope glycoprotein folding and its function in general. 26769631 6 39 gly glycosylation 984:996 arg2 sites 998:1002 these five potential glycosylation sites 963:1002 these five potential glycosylation sites in the F(1) subunit 963:1022 The results showed that four of these five potential glycosylation sites in the F(1) subunit, N293, N361, N526 and N571, were N-glycosylated in F proteins of mature HearNPV budded viruses (BVs) but that N595 was not. 26769631 6 39 gly glycosylation 984:996 arg2 five 969:972 five 969:972 five 969:972 The results showed that four of these five potential glycosylation sites in the F(1) subunit, N293, N361, N526 and N571, were N-glycosylated in F proteins of mature HearNPV budded viruses (BVs) but that N595 was not. 26769631 2 40 theme virus 352:356 arg1 folding 380:386 virus envelope glycoprotein folding 352:386 virus envelope glycoprotein folding 352:386 N-Linked glycosylation of virus envelope glycoprotein is important for virus envelope glycoprotein folding and its function in general. 26769631 5 41 theme located 754:760 arg1 sites 748:752 the other five potential N-glycosylation sites 707:752 the other five potential N-glycosylation sites located in the HaF1 subunit, namely 707:788 In this study, the other five potential N-glycosylation sites located in the HaF1 subunit, namely, N293, N361, N526, N571 and N595, were analysed extensively to examine their N-glycosylation and relative importance to the function of HaF. 26769631 5 41 theme located 754:760 arg1 N361 797:800 N361 797:800 N361 797:800 In this study, the other five potential N-glycosylation sites located in the HaF1 subunit, namely, N293, N361, N526, N571 and N595, were analysed extensively to examine their N-glycosylation and relative importance to the function of HaF. 26769631 5 41 theme located 754:760 arg1 N595 818:821 N595 818:821 N595 818:821 In this study, the other five potential N-glycosylation sites located in the HaF1 subunit, namely, N293, N361, N526, N571 and N595, were analysed extensively to examine their N-glycosylation and relative importance to the function of HaF. 26769631 5 41 theme located 754:760 arg1 N571 809:812 N571 809:812 N571 809:812 In this study, the other five potential N-glycosylation sites located in the HaF1 subunit, namely, N293, N361, N526, N571 and N595, were analysed extensively to examine their N-glycosylation and relative importance to the function of HaF. 26769631 5 41 theme located 754:760 arg1 N526 803:806 N526 803:806 N526 803:806 In this study, the other five potential N-glycosylation sites located in the HaF1 subunit, namely, N293, N361, N526, N571 and N595, were analysed extensively to examine their N-glycosylation and relative importance to the function of HaF. 26769631 9 42 theme HaF 1694:1696 arg1 function 1698:1705 HaF function 1694:1705 HaF function 1694:1705 In summary, N-glycosylation plays comprehensive roles in HaF function and virus infectivity, which is further discussed. 26769631 5 43 gly N-glycosylation 732:746 arg2 N361 797:800 N361 797:800 N361 797:800 In this study, the other five potential N-glycosylation sites located in the HaF1 subunit, namely, N293, N361, N526, N571 and N595, were analysed extensively to examine their N-glycosylation and relative importance to the function of HaF. 26769631 5 43 gly N-glycosylation 732:746 arg2 N595 818:821 N595 818:821 N595 818:821 In this study, the other five potential N-glycosylation sites located in the HaF1 subunit, namely, N293, N361, N526, N571 and N595, were analysed extensively to examine their N-glycosylation and relative importance to the function of HaF. 26769631 5 43 gly N-glycosylation 732:746 arg2 N526 803:806 N526 803:806 N526 803:806 In this study, the other five potential N-glycosylation sites located in the HaF1 subunit, namely, N293, N361, N526, N571 and N595, were analysed extensively to examine their N-glycosylation and relative importance to the function of HaF. 26769631 5 43 gly N-glycosylation 732:746 arg2 sites 748:752 the other five potential N-glycosylation sites 707:752 the other five potential N-glycosylation sites located in the HaF1 subunit, namely 707:788 In this study, the other five potential N-glycosylation sites located in the HaF1 subunit, namely, N293, N361, N526, N571 and N595, were analysed extensively to examine their N-glycosylation and relative importance to the function of HaF. 26769631 5 43 gly N-glycosylation 732:746 arg2 five 717:720 five 717:720 five 717:720 In this study, the other five potential N-glycosylation sites located in the HaF1 subunit, namely, N293, N361, N526, N571 and N595, were analysed extensively to examine their N-glycosylation and relative importance to the function of HaF. 26769631 5 43 gly N-glycosylation 732:746 arg2 N571 809:812 N571 809:812 N571 809:812 In this study, the other five potential N-glycosylation sites located in the HaF1 subunit, namely, N293, N361, N526, N571 and N595, were analysed extensively to examine their N-glycosylation and relative importance to the function of HaF. 26769631 8 44 theme N-glycosylation 1479:1493 arg1 absence 1468:1474 The absence 1464:1474 The absence of N-glycosylation at other individual sites 1464:1519 The absence of N-glycosylation at other individual sites was found to have different effects on the fusogenicity and subcelluar distribution of HaF proteins in HzAM1 cells. 26769631 7 45 from general 1151:1157 arg1 critical 1188:1195 critical 1188:1195 critical 1188:1195 In general, the conserved site N526 was critical to the functioning of HaF, as absence of N-glycosylation of N526 reduced the efficiency of HaF folding and trafficking, consequently decreased fusogenicity and modified the subcellular localization of HaF proteins, and thus impaired virus production and infectivity. 26769631 7 45 from general 1151:1157 arg1 N526 1179:1182 the conserved site N526 1160:1182 the conserved site N526 1160:1182 In general, the conserved site N526 was critical to the functioning of HaF, as absence of N-glycosylation of N526 reduced the efficiency of HaF folding and trafficking, consequently decreased fusogenicity and modified the subcellular localization of HaF proteins, and thus impaired virus production and infectivity. 26769631 3 46 gly N-glycosylation 441:455 arg2 six 427:429 six 427:429 six 427:429 There are six predicted N-glycosylation sites in the F (HaF) protein of Helicoverpa armigera nucleopolyhedrovirus (HearNPV). 26769631 3 46 gly N-glycosylation 441:455 arg2 sites 457:461 six predicted N-glycosylation sites 427:461 six predicted N-glycosylation sites in the F (HaF) protein of Helicoverpa armigera nucleopolyhedrovirus (HearNPV) 427:539 There are six predicted N-glycosylation sites in the F (HaF) protein of Helicoverpa armigera nucleopolyhedrovirus (HearNPV). 26769631 8 47 theme other 1498:1502 arg1 sites 1515:1519 other individual sites 1498:1519 other individual sites 1498:1519 The absence of N-glycosylation at other individual sites was found to have different effects on the fusogenicity and subcelluar distribution of HaF proteins in HzAM1 cells. 26769631 1 48 theme significant 234:244 arg1 role 246:249 a significant role 232:249 a significant role 232:249 The envelope fusion (F) protein of baculoviruses is a heavily N-glycosylated protein that plays a significant role in the virus infection cycle. 26769631 5 49 theme HaF 926:928 arg1 function 914:921 the function 910:921 the function of HaF 910:928 In this study, the other five potential N-glycosylation sites located in the HaF1 subunit, namely, N293, N361, N526, N571 and N595, were analysed extensively to examine their N-glycosylation and relative importance to the function of HaF. 26769631 6 50 theme F 1011:1011 arg1 subunit 1016:1022 the F(1) subunit 1007:1022 the F(1) subunit 1007:1022 The results showed that four of these five potential glycosylation sites in the F(1) subunit, N293, N361, N526 and N571, were N-glycosylated in F proteins of mature HearNPV budded viruses (BVs) but that N595 was not. 26769631 5 51 theme other 711:715 arg1 sites 748:752 the other five potential N-glycosylation sites 707:752 the other five potential N-glycosylation sites located in the HaF1 subunit, namely 707:788 In this study, the other five potential N-glycosylation sites located in the HaF1 subunit, namely, N293, N361, N526, N571 and N595, were analysed extensively to examine their N-glycosylation and relative importance to the function of HaF. 26769631 5 51 theme other 711:715 arg1 N361 797:800 N361 797:800 N361 797:800 In this study, the other five potential N-glycosylation sites located in the HaF1 subunit, namely, N293, N361, N526, N571 and N595, were analysed extensively to examine their N-glycosylation and relative importance to the function of HaF. 26769631 5 51 theme other 711:715 arg1 N595 818:821 N595 818:821 N595 818:821 In this study, the other five potential N-glycosylation sites located in the HaF1 subunit, namely, N293, N361, N526, N571 and N595, were analysed extensively to examine their N-glycosylation and relative importance to the function of HaF. 26769631 5 51 theme other 711:715 arg1 N571 809:812 N571 809:812 N571 809:812 In this study, the other five potential N-glycosylation sites located in the HaF1 subunit, namely, N293, N361, N526, N571 and N595, were analysed extensively to examine their N-glycosylation and relative importance to the function of HaF. 26769631 5 51 theme other 711:715 arg1 N526 803:806 N526 803:806 N526 803:806 In this study, the other five potential N-glycosylation sites located in the HaF1 subunit, namely, N293, N361, N526, N571 and N595, were analysed extensively to examine their N-glycosylation and relative importance to the function of HaF. 26769631 2 52 theme glycoprotein 367:378 arg1 folding 380:386 virus envelope glycoprotein folding 352:386 virus envelope glycoprotein folding 352:386 N-Linked glycosylation of virus envelope glycoprotein is important for virus envelope glycoprotein folding and its function in general. 26769631 7 53 theme HaF 1288:1290 arg1 folding 1292:1298 HaF folding 1288:1298 HaF folding 1288:1298 In general, the conserved site N526 was critical to the functioning of HaF, as absence of N-glycosylation of N526 reduced the efficiency of HaF folding and trafficking, consequently decreased fusogenicity and modified the subcellular localization of HaF proteins, and thus impaired virus production and infectivity. 26769631 4 54 theme F 582:582 arg1 N104 596:599 N104 596:599 N104 596:599 The N-glycosylation site located in the F(2) subunit (N104) of HaF has been identified and functionally characterized previously (Long et al., 2007). 26769631 4 54 theme F 582:582 arg1 subunit 587:593 the F(2) subunit 578:593 the F(2) subunit (N104) of HaF 578:607 The N-glycosylation site located in the F(2) subunit (N104) of HaF has been identified and functionally characterized previously (Long et al., 2007). 26769631 1 55 theme virus 258:262 arg1 cycle 274:278 the virus infection cycle 254:278 the virus infection cycle 254:278 The envelope fusion (F) protein of baculoviruses is a heavily N-glycosylated protein that plays a significant role in the virus infection cycle. 26769631 7 56 theme N526 1257:1260 arg1 absence 1227:1233 absence 1227:1233 absence of N-glycosylation of N526 1227:1260 In general, the conserved site N526 was critical to the functioning of HaF, as absence of N-glycosylation of N526 reduced the efficiency of HaF folding and trafficking, consequently decreased fusogenicity and modified the subcellular localization of HaF proteins, and thus impaired virus production and infectivity. 26769631 1 57 gly N-glycosylated 198:211 arg1 protein 213:219 a heavily N-glycosylated protein 188:219 a heavily N-glycosylated protein that plays a significant role in the virus infection cycle 188:278 The envelope fusion (F) protein of baculoviruses is a heavily N-glycosylated protein that plays a significant role in the virus infection cycle. 26769631 1 57 gly N-glycosylated 198:211 arg1 protein 160:166 The envelope fusion (F) protein 136:166 The envelope fusion (F) protein of baculoviruses 136:183 The envelope fusion (F) protein of baculoviruses is a heavily N-glycosylated protein that plays a significant role in the virus infection cycle. 26769631 0 58 theme glycosylation 47:59 arg1 analysis 26:33 Mutational and functional analysis 0:33 analysis 26:33 Mutational and functional analysis of N-linked glycosylation of envelope fusion protein F of Helicoverpa armigera nucleopolyhedrovirus. 26769631 7 59 theme N-glycosylation 1238:1252 arg1 absence 1227:1233 absence 1227:1233 absence of N-glycosylation of N526 1227:1260 In general, the conserved site N526 was critical to the functioning of HaF, as absence of N-glycosylation of N526 reduced the efficiency of HaF folding and trafficking, consequently decreased fusogenicity and modified the subcellular localization of HaF proteins, and thus impaired virus production and infectivity. 26769631 4 60 from subunit 587:593 arg1 located 567:573 located 567:573 located 567:573 The N-glycosylation site located in the F(2) subunit (N104) of HaF has been identified and functionally characterized previously (Long et al., 2007). 26769631 6 61 theme viruses 1111:1117 arg1 proteins 1077:1084 F proteins 1075:1084 F proteins of mature HearNPV budded viruses (BVs) 1075:1123 The results showed that four of these five potential glycosylation sites in the F(1) subunit, N293, N361, N526 and N571, were N-glycosylated in F proteins of mature HearNPV budded viruses (BVs) but that N595 was not. 26769631 2 62 theme glycoprotein 322:333 arg1 glycosylation 290:302 N-Linked glycosylation 281:302 N-Linked glycosylation of virus envelope glycoprotein 281:333 N-Linked glycosylation of virus envelope glycoprotein is important for virus envelope glycoprotein folding and its function in general. 26769631 0 63 link N-linked 38:45 arg1 glycosylation 47:59 N-linked glycosylation 38:59 N-linked glycosylation of envelope fusion protein F of Helicoverpa armigera nucleopolyhedrovirus 38:133 Mutational and functional analysis of N-linked glycosylation of envelope fusion protein F of Helicoverpa armigera nucleopolyhedrovirus. 26769631 8 64 from distribution 1592:1603 arg1 cells 1630:1634 HzAM1 cells 1624:1634 HzAM1 cells 1624:1634 The absence of N-glycosylation at other individual sites was found to have different effects on the fusogenicity and subcelluar distribution of HaF proteins in HzAM1 cells. 26769631 2 65 theme virus 307:311 arg1 glycoprotein 322:333 virus envelope glycoprotein 307:333 virus envelope glycoprotein 307:333 N-Linked glycosylation of virus envelope glycoprotein is important for virus envelope glycoprotein folding and its function in general. 26769631 3 66 theme armigera 501:508 arg1 nucleopolyhedrovirus 510:529 Helicoverpa armigera nucleopolyhedrovirus 489:529 Helicoverpa armigera nucleopolyhedrovirus (HearNPV) 489:539 There are six predicted N-glycosylation sites in the F (HaF) protein of Helicoverpa armigera nucleopolyhedrovirus (HearNPV). 26769631 3 66 theme armigera 501:508 arg1 HearNPV 532:538 HearNPV 532:538 HearNPV 532:538 There are six predicted N-glycosylation sites in the F (HaF) protein of Helicoverpa armigera nucleopolyhedrovirus (HearNPV). 26769631 6 67 theme mature 1089:1094 arg1 BVs 1120:1122 BVs 1120:1122 BVs 1120:1122 The results showed that four of these five potential glycosylation sites in the F(1) subunit, N293, N361, N526 and N571, were N-glycosylated in F proteins of mature HearNPV budded viruses (BVs) but that N595 was not. 26769631 6 67 theme mature 1089:1094 arg1 viruses 1111:1117 mature HearNPV budded viruses 1089:1117 mature HearNPV budded viruses (BVs) 1089:1123 The results showed that four of these five potential glycosylation sites in the F(1) subunit, N293, N361, N526 and N571, were N-glycosylated in F proteins of mature HearNPV budded viruses (BVs) but that N595 was not. 26769631 7 68 theme virus 1430:1434 arg1 production 1436:1445 virus production 1430:1445 virus production 1430:1445 In general, the conserved site N526 was critical to the functioning of HaF, as absence of N-glycosylation of N526 reduced the efficiency of HaF folding and trafficking, consequently decreased fusogenicity and modified the subcellular localization of HaF proteins, and thus impaired virus production and infectivity. 26769631 8 69 theme HaF 1608:1610 arg1 proteins 1612:1619 HaF proteins 1608:1619 HaF proteins 1608:1619 The absence of N-glycosylation at other individual sites was found to have different effects on the fusogenicity and subcelluar distribution of HaF proteins in HzAM1 cells. 26769631 1 70 theme envelope 140:147 arg1 protein 213:219 a heavily N-glycosylated protein 188:219 a heavily N-glycosylated protein that plays a significant role in the virus infection cycle 188:278 The envelope fusion (F) protein of baculoviruses is a heavily N-glycosylated protein that plays a significant role in the virus infection cycle. 26769631 1 70 theme envelope 140:147 arg1 protein 160:166 The envelope fusion (F) protein 136:166 The envelope fusion (F) protein of baculoviruses 136:183 The envelope fusion (F) protein of baculoviruses is a heavily N-glycosylated protein that plays a significant role in the virus infection cycle. 26769631 0 71 theme fusion 73:78 arg1 F 88:88 envelope fusion protein F 64:88 envelope fusion protein F of Helicoverpa armigera nucleopolyhedrovirus 64:133 Mutational and functional analysis of N-linked glycosylation of envelope fusion protein F of Helicoverpa armigera nucleopolyhedrovirus. 26769631 6 72 from N-glycosylated 1057:1070 arg1 proteins 1077:1084 F proteins 1075:1084 F proteins of mature HearNPV budded viruses (BVs) 1075:1123 The results showed that four of these five potential glycosylation sites in the F(1) subunit, N293, N361, N526 and N571, were N-glycosylated in F proteins of mature HearNPV budded viruses (BVs) but that N595 was not. 26769631 0 73 theme F 88:88 arg1 glycosylation 47:59 N-linked glycosylation 38:59 N-linked glycosylation of envelope fusion protein F of Helicoverpa armigera nucleopolyhedrovirus 38:133 Mutational and functional analysis of N-linked glycosylation of envelope fusion protein F of Helicoverpa armigera nucleopolyhedrovirus. 26769631 5 74 from located 754:760 arg1 subunit 774:780 the HaF1 subunit 765:780 the HaF1 subunit 765:780 In this study, the other five potential N-glycosylation sites located in the HaF1 subunit, namely, N293, N361, N526, N571 and N595, were analysed extensively to examine their N-glycosylation and relative importance to the function of HaF. 26769631 4 75 gly N-glycosylation 546:560 arg2 site 562:565 The N-glycosylation site 542:565 The N-glycosylation site located in the F(2) subunit (N104) of HaF 542:607 The N-glycosylation site located in the F(2) subunit (N104) of HaF has been identified and functionally characterized previously (Long et al., 2007). 26769631 7 76 theme HaF 1398:1400 arg1 proteins 1402:1409 HaF proteins 1398:1409 HaF proteins 1398:1409 In general, the conserved site N526 was critical to the functioning of HaF, as absence of N-glycosylation of N526 reduced the efficiency of HaF folding and trafficking, consequently decreased fusogenicity and modified the subcellular localization of HaF proteins, and thus impaired virus production and infectivity. 26769631 0 77 theme Helicoverpa 93:103 arg1 nucleopolyhedrovirus 114:133 Helicoverpa armigera nucleopolyhedrovirus 93:133 Helicoverpa armigera nucleopolyhedrovirus 93:133 Mutational and functional analysis of N-linked glycosylation of envelope fusion protein F of Helicoverpa armigera nucleopolyhedrovirus. 26769631 8 78 dep fusogenicity 1564:1575 arg1 the 1560:1562 the 1560:1562 the 1560:1562 The absence of N-glycosylation at other individual sites was found to have different effects on the fusogenicity and subcelluar distribution of HaF proteins in HzAM1 cells. 26769631 0 79 theme nucleopolyhedrovirus 114:133 arg1 F 88:88 envelope fusion protein F 64:88 envelope fusion protein F of Helicoverpa armigera nucleopolyhedrovirus 64:133 Mutational and functional analysis of N-linked glycosylation of envelope fusion protein F of Helicoverpa armigera nucleopolyhedrovirus. 26769631 5 80 from subunit 774:780 arg1 located 754:760 located 754:760 located 754:760 In this study, the other five potential N-glycosylation sites located in the HaF1 subunit, namely, N293, N361, N526, N571 and N595, were analysed extensively to examine their N-glycosylation and relative importance to the function of HaF. 26769631 6 81 theme sites 998:1002 arg1 N361 1031:1034 N361 1031:1034 N361 1031:1034 The results showed that four of these five potential glycosylation sites in the F(1) subunit, N293, N361, N526 and N571, were N-glycosylated in F proteins of mature HearNPV budded viruses (BVs) but that N595 was not. 26769631 6 81 theme sites 998:1002 arg1 N571 1046:1049 N571 1046:1049 N571 1046:1049 The results showed that four of these five potential glycosylation sites in the F(1) subunit, N293, N361, N526 and N571, were N-glycosylated in F proteins of mature HearNPV budded viruses (BVs) but that N595 was not. 26769631 6 81 theme sites 998:1002 arg1 four 955:958 four 955:958 four 955:958 The results showed that four of these five potential glycosylation sites in the F(1) subunit, N293, N361, N526 and N571, were N-glycosylated in F proteins of mature HearNPV budded viruses (BVs) but that N595 was not. 26769631 6 81 theme sites 998:1002 arg1 N526 1037:1040 N526 1037:1040 N526 1037:1040 The results showed that four of these five potential glycosylation sites in the F(1) subunit, N293, N361, N526 and N571, were N-glycosylated in F proteins of mature HearNPV budded viruses (BVs) but that N595 was not. 26769631 6 81 theme sites 998:1002 arg1 sites 998:1002 these five potential glycosylation sites 963:1002 these five potential glycosylation sites in the F(1) subunit 963:1022 The results showed that four of these five potential glycosylation sites in the F(1) subunit, N293, N361, N526 and N571, were N-glycosylated in F proteins of mature HearNPV budded viruses (BVs) but that N595 was not. 26769631 7 82 from critical 1188:1195 arg1 general 1151:1157 general 1151:1157 general 1151:1157 In general, the conserved site N526 was critical to the functioning of HaF, as absence of N-glycosylation of N526 reduced the efficiency of HaF folding and trafficking, consequently decreased fusogenicity and modified the subcellular localization of HaF proteins, and thus impaired virus production and infectivity. 26769631 6 83 theme potential 974:982 arg1 sites 998:1002 these five potential glycosylation sites 963:1002 these five potential glycosylation sites in the F(1) subunit 963:1022 The results showed that four of these five potential glycosylation sites in the F(1) subunit, N293, N361, N526 and N571, were N-glycosylated in F proteins of mature HearNPV budded viruses (BVs) but that N595 was not. 26769631 4 84 theme located 567:573 arg1 site 562:565 The N-glycosylation site 542:565 The N-glycosylation site located in the F(2) subunit (N104) of HaF 542:607 The N-glycosylation site located in the F(2) subunit (N104) of HaF has been identified and functionally characterized previously (Long et al., 2007). 26769631 3 85 theme N-glycosylation 441:455 arg1 sites 457:461 six predicted N-glycosylation sites 427:461 six predicted N-glycosylation sites in the F (HaF) protein of Helicoverpa armigera nucleopolyhedrovirus (HearNPV) 427:539 There are six predicted N-glycosylation sites in the F (HaF) protein of Helicoverpa armigera nucleopolyhedrovirus (HearNPV). 26769631 4 86 from located 567:573 arg1 N104 596:599 N104 596:599 N104 596:599 The N-glycosylation site located in the F(2) subunit (N104) of HaF has been identified and functionally characterized previously (Long et al., 2007). 26769631 4 86 from located 567:573 arg1 subunit 587:593 the F(2) subunit 578:593 the F(2) subunit (N104) of HaF 578:607 The N-glycosylation site located in the F(2) subunit (N104) of HaF has been identified and functionally characterized previously (Long et al., 2007). 26769631 8 87 from fusogenicity 1564:1575 arg1 cells 1630:1634 HzAM1 cells 1624:1634 HzAM1 cells 1624:1634 The absence of N-glycosylation at other individual sites was found to have different effects on the fusogenicity and subcelluar distribution of HaF proteins in HzAM1 cells. 26769631 8 88 from sites 1515:1519 arg1 absence 1468:1474 The absence 1464:1474 The absence of N-glycosylation at other individual sites 1464:1519 The absence of N-glycosylation at other individual sites was found to have different effects on the fusogenicity and subcelluar distribution of HaF proteins in HzAM1 cells. 26769631 3 89 theme HaF 473:475 arg1 protein 478:484 the F (HaF) protein 466:484 the F (HaF) protein of Helicoverpa armigera nucleopolyhedrovirus (HearNPV) 466:539 There are six predicted N-glycosylation sites in the F (HaF) protein of Helicoverpa armigera nucleopolyhedrovirus (HearNPV). 26769631 5 90 theme potential 722:730 arg1 sites 748:752 the other five potential N-glycosylation sites 707:752 the other five potential N-glycosylation sites located in the HaF1 subunit, namely 707:788 In this study, the other five potential N-glycosylation sites located in the HaF1 subunit, namely, N293, N361, N526, N571 and N595, were analysed extensively to examine their N-glycosylation and relative importance to the function of HaF. 26769631 5 90 theme potential 722:730 arg1 N361 797:800 N361 797:800 N361 797:800 In this study, the other five potential N-glycosylation sites located in the HaF1 subunit, namely, N293, N361, N526, N571 and N595, were analysed extensively to examine their N-glycosylation and relative importance to the function of HaF. 26769631 5 90 theme potential 722:730 arg1 N595 818:821 N595 818:821 N595 818:821 In this study, the other five potential N-glycosylation sites located in the HaF1 subunit, namely, N293, N361, N526, N571 and N595, were analysed extensively to examine their N-glycosylation and relative importance to the function of HaF. 26769631 5 90 theme potential 722:730 arg1 N571 809:812 N571 809:812 N571 809:812 In this study, the other five potential N-glycosylation sites located in the HaF1 subunit, namely, N293, N361, N526, N571 and N595, were analysed extensively to examine their N-glycosylation and relative importance to the function of HaF. 26769631 5 90 theme potential 722:730 arg1 N526 803:806 N526 803:806 N526 803:806 In this study, the other five potential N-glycosylation sites located in the HaF1 subunit, namely, N293, N361, N526, N571 and N595, were analysed extensively to examine their N-glycosylation and relative importance to the function of HaF. 26769631 7 91 theme subcellular 1370:1380 arg1 localization 1382:1393 the subcellular localization 1366:1393 the subcellular localization of HaF proteins 1366:1409 In general, the conserved site N526 was critical to the functioning of HaF, as absence of N-glycosylation of N526 reduced the efficiency of HaF folding and trafficking, consequently decreased fusogenicity and modified the subcellular localization of HaF proteins, and thus impaired virus production and infectivity. 26769631 9 92 theme virus 1711:1715 arg1 infectivity 1717:1727 virus infectivity 1711:1727 virus infectivity 1711:1727 In summary, N-glycosylation plays comprehensive roles in HaF function and virus infectivity, which is further discussed. 26769631 9 93 theme comprehensive 1671:1683 arg1 roles 1685:1689 comprehensive roles 1671:1689 comprehensive roles 1671:1689 In summary, N-glycosylation plays comprehensive roles in HaF function and virus infectivity, which is further discussed. 26769631 2 94 gly glycoprotein 367:378 arg1 glycoprotein 367:378 virus envelope glycoprotein folding 352:386 virus envelope glycoprotein folding 352:386 N-Linked glycosylation of virus envelope glycoprotein is important for virus envelope glycoprotein folding and its function in general. 26769631 3 95 theme F 470:470 arg1 protein 478:484 the F (HaF) protein 466:484 the F (HaF) protein of Helicoverpa armigera nucleopolyhedrovirus (HearNPV) 466:539 There are six predicted N-glycosylation sites in the F (HaF) protein of Helicoverpa armigera nucleopolyhedrovirus (HearNPV). 26769631 4 96 theme N-glycosylation 546:560 arg1 site 562:565 The N-glycosylation site 542:565 The N-glycosylation site located in the F(2) subunit (N104) of HaF 542:607 The N-glycosylation site located in the F(2) subunit (N104) of HaF has been identified and functionally characterized previously (Long et al., 2007). 26769631 3 97 theme Helicoverpa 489:499 arg1 nucleopolyhedrovirus 510:529 Helicoverpa armigera nucleopolyhedrovirus 489:529 Helicoverpa armigera nucleopolyhedrovirus (HearNPV) 489:539 There are six predicted N-glycosylation sites in the F (HaF) protein of Helicoverpa armigera nucleopolyhedrovirus (HearNPV). 26769631 3 97 theme Helicoverpa 489:499 arg1 HearNPV 532:538 HearNPV 532:538 HearNPV 532:538 There are six predicted N-glycosylation sites in the F (HaF) protein of Helicoverpa armigera nucleopolyhedrovirus (HearNPV). 26769631 4 98 dep characterized 646:658 arg1 2007 685:688 2007 685:688 2007 685:688 The N-glycosylation site located in the F(2) subunit (N104) of HaF has been identified and functionally characterized previously (Long et al., 2007). 26769631 8 99 theme individual 1504:1513 arg1 sites 1515:1519 other individual sites 1498:1519 other individual sites 1498:1519 The absence of N-glycosylation at other individual sites was found to have different effects on the fusogenicity and subcelluar distribution of HaF proteins in HzAM1 cells. 26769631 0 100 gly glycosylation 47:59 arg1 F 88:88 envelope fusion protein F 64:88 envelope fusion protein F of Helicoverpa armigera nucleopolyhedrovirus 64:133 Mutational and functional analysis of N-linked glycosylation of envelope fusion protein F of Helicoverpa armigera nucleopolyhedrovirus. 26769631 6 101 theme glycosylation 984:996 arg1 sites 998:1002 these five potential glycosylation sites 963:1002 these five potential glycosylation sites in the F(1) subunit 963:1022 The results showed that four of these five potential glycosylation sites in the F(1) subunit, N293, N361, N526 and N571, were N-glycosylated in F proteins of mature HearNPV budded viruses (BVs) but that N595 was not. 26769631 2 102 gly glycoprotein 322:333 arg1 glycoprotein 322:333 virus envelope glycoprotein 307:333 virus envelope glycoprotein 307:333 N-Linked glycosylation of virus envelope glycoprotein is important for virus envelope glycoprotein folding and its function in general. 26769631 3 103 from sites 457:461 arg1 protein 478:484 the F (HaF) protein 466:484 the F (HaF) protein of Helicoverpa armigera nucleopolyhedrovirus (HearNPV) 466:539 There are six predicted N-glycosylation sites in the F (HaF) protein of Helicoverpa armigera nucleopolyhedrovirus (HearNPV). 26709950 6 0 theme N-linked 984:991 arg1 oligosaccharides 993:1008 N-linked oligosaccharides 984:1008 N-linked oligosaccharides 984:1008 Biochemical and histochemical assays were used to verify whether N-linked oligosaccharides were removed from bone matrix by PNGase F. By testing wet and dehydrated bone specimens, the coupling effect between water and PGs on the in situ toughness of bone was investigated. 26709950 7 1 theme wet 1299:1301 arg1 samples 1308:1314 wet bone samples 1299:1314 wet bone samples 1299:1314 The two-way ANOVA analyses showed that removal of GAGs had significant effects on the in situ toughness of wet bone samples. 26709950 6 2 theme in 1148:1149 arg1 toughness 1156:1164 the in situ toughness 1144:1164 the in situ toughness of bone 1144:1172 Biochemical and histochemical assays were used to verify whether N-linked oligosaccharides were removed from bone matrix by PNGase F. By testing wet and dehydrated bone specimens, the coupling effect between water and PGs on the in situ toughness of bone was investigated. 26709950 4 3 theme bone 606:609 arg1 toughness 577:585 the in situ toughness 565:585 the in situ toughness of human cadaveric bone treated with and without peptide-N-glycosidase F (PNGase F), an enzyme that specifically removes the N-linked oligosaccharides of GAGs from core proteins 565:763 To test the hypothesis, we used a novel nanoscratch test to measure the in situ toughness of human cadaveric bone treated with and without peptide-N-glycosidase F (PNGase F), an enzyme that specifically removes the N-linked oligosaccharides of GAGs from core proteins. 26709950 6 4 theme wet 1064:1066 arg1 specimens 1088:1096 wet and dehydrated bone specimens 1064:1096 wet and dehydrated bone specimens 1064:1096 Biochemical and histochemical assays were used to verify whether N-linked oligosaccharides were removed from bone matrix by PNGase F. By testing wet and dehydrated bone specimens, the coupling effect between water and PGs on the in situ toughness of bone was investigated. 26709950 7 5 theme in 1278:1279 arg1 toughness 1286:1294 the in situ toughness 1274:1294 the in situ toughness of wet bone samples 1274:1314 The two-way ANOVA analyses showed that removal of GAGs had significant effects on the in situ toughness of wet bone samples. 26709950 4 6 theme in 569:570 arg1 toughness 577:585 the in situ toughness 565:585 the in situ toughness of human cadaveric bone treated with and without peptide-N-glycosidase F (PNGase F), an enzyme that specifically removes the N-linked oligosaccharides of GAGs from core proteins 565:763 To test the hypothesis, we used a novel nanoscratch test to measure the in situ toughness of human cadaveric bone treated with and without peptide-N-glycosidase F (PNGase F), an enzyme that specifically removes the N-linked oligosaccharides of GAGs from core proteins. 26709950 5 7 theme Cortical 766:773 arg1 specimens 780:788 Cortical bone specimens 766:788 Cortical bone specimens 766:788 Cortical bone specimens were prepared from the posterior aspect of mid-diaphyseal femurs of six (n = 6) male human donors between 51.5 ± 5.17 years old. 26709950 4 8 theme novel 531:535 arg1 test 549:552 a novel nanoscratch test 529:552 a novel nanoscratch test 529:552 To test the hypothesis, we used a novel nanoscratch test to measure the in situ toughness of human cadaveric bone treated with and without peptide-N-glycosidase F (PNGase F), an enzyme that specifically removes the N-linked oligosaccharides of GAGs from core proteins. 26709950 4 9 used used 524:527 arg2 we 521:522 we 521:522 we 521:522 To test the hypothesis, we used a novel nanoscratch test to measure the in situ toughness of human cadaveric bone treated with and without peptide-N-glycosidase F (PNGase F), an enzyme that specifically removes the N-linked oligosaccharides of GAGs from core proteins. 26709950 1 10 theme bone 168:171 arg1 matrix 158:163 the extracellular matrix 140:163 the extracellular matrix of bone 140:171 Proteoglycans (PGs) are one type of noncollagenous proteins in the extracellular matrix of bone that primarily contain a core protein and glycosaminoglycans (GAGs). 26709950 7 11 theme significant 1251:1261 arg1 effects 1263:1269 significant effects 1251:1269 significant effects 1251:1269 The two-way ANOVA analyses showed that removal of GAGs had significant effects on the in situ toughness of wet bone samples. 26709950 7 12 theme GAGs 1242:1245 arg1 removal 1231:1237 removal 1231:1237 removal of GAGs 1231:1245 The two-way ANOVA analyses showed that removal of GAGs had significant effects on the in situ toughness of wet bone samples. 26709950 2 13 dep polar 258:262 arg1 have 293:296 have 293:296 have a strong tendency to attract water molecules into the matrix 293:357 GAGs are highly polar and negatively charged, thus have a strong tendency to attract water molecules into the matrix. 26709950 1 14 contain contain 188:194 arg2 GAGs 235:238 GAGs 235:238 GAGs 235:238 Proteoglycans (PGs) are one type of noncollagenous proteins in the extracellular matrix of bone that primarily contain a core protein and glycosaminoglycans (GAGs). 26709950 1 14 contain contain 188:194 arg1 Proteoglycans 77:89 Proteoglycans 77:89 Proteoglycans (PGs) 77:95 Proteoglycans (PGs) are one type of noncollagenous proteins in the extracellular matrix of bone that primarily contain a core protein and glycosaminoglycans (GAGs). 26709950 1 14 contain contain 188:194 arg2 glycosaminoglycans 215:232 glycosaminoglycans 215:232 glycosaminoglycans (GAGs) 215:239 Proteoglycans (PGs) are one type of noncollagenous proteins in the extracellular matrix of bone that primarily contain a core protein and glycosaminoglycans (GAGs). 26709950 1 14 contain contain 188:194 arg2 protein 203:209 a core protein 196:209 a core protein 196:209 Proteoglycans (PGs) are one type of noncollagenous proteins in the extracellular matrix of bone that primarily contain a core protein and glycosaminoglycans (GAGs). 26709950 1 14 contain contain 188:194 arg1 type 105:108 one type 101:108 one type of noncollagenous proteins in the extracellular matrix of bone that primarily contain a core protein and glycosaminoglycans (GAGs) 101:239 Proteoglycans (PGs) are one type of noncollagenous proteins in the extracellular matrix of bone that primarily contain a core protein and glycosaminoglycans (GAGs). 26709950 6 15 theme bone 1169:1172 arg1 toughness 1156:1164 the in situ toughness 1144:1164 the in situ toughness of bone 1144:1172 Biochemical and histochemical assays were used to verify whether N-linked oligosaccharides were removed from bone matrix by PNGase F. By testing wet and dehydrated bone specimens, the coupling effect between water and PGs on the in situ toughness of bone was investigated. 26709950 6 16 theme dehydrated 1072:1081 arg1 specimens 1088:1096 wet and dehydrated bone specimens 1064:1096 wet and dehydrated bone specimens 1064:1096 Biochemical and histochemical assays were used to verify whether N-linked oligosaccharides were removed from bone matrix by PNGase F. By testing wet and dehydrated bone specimens, the coupling effect between water and PGs on the in situ toughness of bone was investigated. 26709950 0 17 theme In 50:51 arg1 Toughness 58:66 the In Situ Toughness 46:66 the In Situ Toughness of Bone 46:74 Coupling Effect of Water and Proteoglycans on the In Situ Toughness of Bone. 26709950 8 18 theme GAGs 1345:1348 arg1 removal 1334:1340 the removal 1330:1340 the removal of GAGs 1330:1348 In contrast, the removal of GAGs did not show significant effects on the toughness of dry bone. 26709950 4 19 theme human 590:594 arg1 bone 606:609 human cadaveric bone 590:609 human cadaveric bone treated with and without peptide-N-glycosidase F (PNGase F), an enzyme that specifically removes the N-linked oligosaccharides of GAGs from core proteins 590:763 To test the hypothesis, we used a novel nanoscratch test to measure the in situ toughness of human cadaveric bone treated with and without peptide-N-glycosidase F (PNGase F), an enzyme that specifically removes the N-linked oligosaccharides of GAGs from core proteins. 26709950 9 20 dep in 1505:1506 arg1 situ 1508:1511 situ 1508:1511 situ 1508:1511 The results of this study, for the first time, suggest that GAGs play a pivotal role in the in situ toughness of bone only when water is present, and vice versa, water functions as a plasticizer in bone only when GAGs are present. 26709950 4 21 from proteins 756:763 arg1 GAGs 741:744 GAGs 741:744 GAGs from core proteins 741:763 To test the hypothesis, we used a novel nanoscratch test to measure the in situ toughness of human cadaveric bone treated with and without peptide-N-glycosidase F (PNGase F), an enzyme that specifically removes the N-linked oligosaccharides of GAGs from core proteins. 26709950 4 21 from proteins 756:763 arg1 oligosaccharides 721:736 the N-linked oligosaccharides 708:736 the N-linked oligosaccharides of GAGs from core proteins 708:763 To test the hypothesis, we used a novel nanoscratch test to measure the in situ toughness of human cadaveric bone treated with and without peptide-N-glycosidase F (PNGase F), an enzyme that specifically removes the N-linked oligosaccharides of GAGs from core proteins. 26709950 1 22 theme proteins 128:135 arg1 Proteoglycans 77:89 Proteoglycans 77:89 Proteoglycans (PGs) 77:95 Proteoglycans (PGs) are one type of noncollagenous proteins in the extracellular matrix of bone that primarily contain a core protein and glycosaminoglycans (GAGs). 26709950 1 22 theme proteins 128:135 arg1 type 105:108 one type 101:108 one type of noncollagenous proteins in the extracellular matrix of bone that primarily contain a core protein and glycosaminoglycans (GAGs) 101:239 Proteoglycans (PGs) are one type of noncollagenous proteins in the extracellular matrix of bone that primarily contain a core protein and glycosaminoglycans (GAGs). 26709950 4 23 theme PNGase 661:666 arg1 F 658:658 peptide-N-glycosidase F 636:658 peptide-N-glycosidase F (PNGase F) 636:669 To test the hypothesis, we used a novel nanoscratch test to measure the in situ toughness of human cadaveric bone treated with and without peptide-N-glycosidase F (PNGase F), an enzyme that specifically removes the N-linked oligosaccharides of GAGs from core proteins. 26709950 4 23 theme PNGase 661:666 arg1 F 668:668 PNGase F 661:668 PNGase F 661:668 To test the hypothesis, we used a novel nanoscratch test to measure the in situ toughness of human cadaveric bone treated with and without peptide-N-glycosidase F (PNGase F), an enzyme that specifically removes the N-linked oligosaccharides of GAGs from core proteins. 26709950 0 24 theme Bone 71:74 arg1 Toughness 58:66 the In Situ Toughness 46:66 the In Situ Toughness of Bone 46:74 Coupling Effect of Water and Proteoglycans on the In Situ Toughness of Bone. 26709950 1 25 from type 105:108 arg1 matrix 158:163 the extracellular matrix 140:163 the extracellular matrix of bone 140:171 Proteoglycans (PGs) are one type of noncollagenous proteins in the extracellular matrix of bone that primarily contain a core protein and glycosaminoglycans (GAGs). 26709950 8 26 theme significant 1363:1373 arg1 effects 1375:1381 significant effects 1363:1381 significant effects on the toughness of dry bone 1363:1410 In contrast, the removal of GAGs did not show significant effects on the toughness of dry bone. 26709950 2 27 theme water 327:331 arg1 molecules 333:341 water molecules 327:341 water molecules 327:341 GAGs are highly polar and negatively charged, thus have a strong tendency to attract water molecules into the matrix. 26709950 0 28 theme Coupling 0:7 arg1 Effect 9:14 Coupling Effect 0:14 Coupling Effect of Water and Proteoglycans on the In Situ Toughness of Bone. 0:75 Coupling Effect of Water and Proteoglycans on the In Situ Toughness of Bone. 26709950 5 29 theme mid-diaphyseal 833:846 arg1 femurs 848:853 mid-diaphyseal femurs 833:853 mid-diaphyseal femurs of six (n = 6) male human donors 833:886 Cortical bone specimens were prepared from the posterior aspect of mid-diaphyseal femurs of six (n = 6) male human donors between 51.5 ± 5.17 years old. 26709950 7 30 theme two-way 1196:1202 arg1 ANOVA 1204:1208 two-way ANOVA 1196:1208 The two-way ANOVA analyses 1192:1217 The two-way ANOVA analyses showed that removal of GAGs had significant effects on the in situ toughness of wet bone samples. 26709950 0 31 dep In 50:51 arg1 Situ 53:56 Situ 53:56 Situ 53:56 Coupling Effect of Water and Proteoglycans on the In Situ Toughness of Bone. 26709950 6 32 theme histochemical 935:947 arg1 assays 949:954 Biochemical and histochemical assays 919:954 Biochemical and histochemical assays 919:954 Biochemical and histochemical assays were used to verify whether N-linked oligosaccharides were removed from bone matrix by PNGase F. By testing wet and dehydrated bone specimens, the coupling effect between water and PGs on the in situ toughness of bone was investigated. 26709950 8 33 theme dry 1403:1405 arg1 bone 1407:1410 dry bone 1403:1410 dry bone 1403:1410 In contrast, the removal of GAGs did not show significant effects on the toughness of dry bone. 26709950 9 34 theme study 1433:1437 arg1 results 1417:1423 The results 1413:1423 The results of this study 1413:1437 The results of this study, for the first time, suggest that GAGs play a pivotal role in the in situ toughness of bone only when water is present, and vice versa, water functions as a plasticizer in bone only when GAGs are present. 26709950 6 35 theme Biochemical 919:929 arg1 assays 949:954 Biochemical and histochemical assays 919:954 Biochemical and histochemical assays 919:954 Biochemical and histochemical assays were used to verify whether N-linked oligosaccharides were removed from bone matrix by PNGase F. By testing wet and dehydrated bone specimens, the coupling effect between water and PGs on the in situ toughness of bone was investigated. 26709950 4 36 theme N-linked 712:719 arg1 oligosaccharides 721:736 the N-linked oligosaccharides 708:736 the N-linked oligosaccharides of GAGs from core proteins 708:763 To test the hypothesis, we used a novel nanoscratch test to measure the in situ toughness of human cadaveric bone treated with and without peptide-N-glycosidase F (PNGase F), an enzyme that specifically removes the N-linked oligosaccharides of GAGs from core proteins. 26709950 3 37 from PGs 395:397 arg1 bone 402:405 bone 402:405 bone 402:405 We hypothesized in this study that PGs in bone play a pivotal role in sustaining the toughness of the tissue only when water is present. 26709950 3 38 theme pivotal 414:420 arg1 role 422:425 a pivotal role 412:425 a pivotal role 412:425 We hypothesized in this study that PGs in bone play a pivotal role in sustaining the toughness of the tissue only when water is present. 26709950 6 39 theme bone 1028:1031 arg1 matrix 1033:1038 bone matrix 1028:1038 bone matrix 1028:1038 Biochemical and histochemical assays were used to verify whether N-linked oligosaccharides were removed from bone matrix by PNGase F. By testing wet and dehydrated bone specimens, the coupling effect between water and PGs on the in situ toughness of bone was investigated. 26709950 5 40 theme human 875:879 arg1 donors 881:886 six (n = 6) male human donors 858:886 six (n = 6) male human donors 858:886 Cortical bone specimens were prepared from the posterior aspect of mid-diaphyseal femurs of six (n = 6) male human donors between 51.5 ± 5.17 years old. 26709950 1 41 theme core 198:201 arg1 protein 203:209 a core protein 196:209 a core protein 196:209 Proteoglycans (PGs) are one type of noncollagenous proteins in the extracellular matrix of bone that primarily contain a core protein and glycosaminoglycans (GAGs). 26709950 2 42 theme strong 300:305 arg1 tendency 307:314 a strong tendency 298:314 a strong tendency to attract water molecules into the matrix 298:357 GAGs are highly polar and negatively charged, thus have a strong tendency to attract water molecules into the matrix. 26709950 7 43 contain had 1247:1249 arg1 removal 1231:1237 removal 1231:1237 removal of GAGs 1231:1245 The two-way ANOVA analyses showed that removal of GAGs had significant effects on the in situ toughness of wet bone samples. 26709950 7 43 contain had 1247:1249 arg2 effects 1263:1269 significant effects 1251:1269 significant effects 1251:1269 The two-way ANOVA analyses showed that removal of GAGs had significant effects on the in situ toughness of wet bone samples. 26709950 9 44 from plasticizer 1596:1606 arg1 bone 1611:1614 bone 1611:1614 bone 1611:1614 The results of this study, for the first time, suggest that GAGs play a pivotal role in the in situ toughness of bone only when water is present, and vice versa, water functions as a plasticizer in bone only when GAGs are present. 26709950 4 45 theme core 751:754 arg1 proteins 756:763 core proteins 751:763 core proteins 751:763 To test the hypothesis, we used a novel nanoscratch test to measure the in situ toughness of human cadaveric bone treated with and without peptide-N-glycosidase F (PNGase F), an enzyme that specifically removes the N-linked oligosaccharides of GAGs from core proteins. 26709950 3 46 theme tissue 462:467 arg1 toughness 445:453 the toughness 441:453 the toughness of the tissue 441:467 We hypothesized in this study that PGs in bone play a pivotal role in sustaining the toughness of the tissue only when water is present. 26709950 6 47 dep in 1148:1149 arg1 situ 1151:1154 situ 1151:1154 situ 1151:1154 Biochemical and histochemical assays were used to verify whether N-linked oligosaccharides were removed from bone matrix by PNGase F. By testing wet and dehydrated bone specimens, the coupling effect between water and PGs on the in situ toughness of bone was investigated. 26709950 7 48 theme bone 1303:1306 arg1 samples 1308:1314 wet bone samples 1299:1314 wet bone samples 1299:1314 The two-way ANOVA analyses showed that removal of GAGs had significant effects on the in situ toughness of wet bone samples. 26709950 7 49 theme samples 1308:1314 arg1 toughness 1286:1294 the in situ toughness 1274:1294 the in situ toughness of wet bone samples 1274:1314 The two-way ANOVA analyses showed that removal of GAGs had significant effects on the in situ toughness of wet bone samples. 26709950 9 50 theme pivotal 1485:1491 arg1 role 1493:1496 a pivotal role 1483:1496 a pivotal role 1483:1496 The results of this study, for the first time, suggest that GAGs play a pivotal role in the in situ toughness of bone only when water is present, and vice versa, water functions as a plasticizer in bone only when GAGs are present. 26709950 10 51 theme Mineral 1681:1687 arg1 Research 1689:1696 Mineral Research 1681:1696 Mineral Research 1681:1696 © 2015 American Society for Bone and Mineral Research. 26709950 1 52 theme extracellular 144:156 arg1 matrix 158:163 the extracellular matrix 140:163 the extracellular matrix of bone 140:171 Proteoglycans (PGs) are one type of noncollagenous proteins in the extracellular matrix of bone that primarily contain a core protein and glycosaminoglycans (GAGs). 26709950 4 53 theme GAGs 741:744 arg1 oligosaccharides 721:736 the N-linked oligosaccharides 708:736 the N-linked oligosaccharides of GAGs from core proteins 708:763 To test the hypothesis, we used a novel nanoscratch test to measure the in situ toughness of human cadaveric bone treated with and without peptide-N-glycosidase F (PNGase F), an enzyme that specifically removes the N-linked oligosaccharides of GAGs from core proteins. 26709950 9 54 theme in 1505:1506 arg1 toughness 1513:1521 the in situ toughness 1501:1521 the in situ toughness of bone 1501:1529 The results of this study, for the first time, suggest that GAGs play a pivotal role in the in situ toughness of bone only when water is present, and vice versa, water functions as a plasticizer in bone only when GAGs are present. 26709950 4 55 theme nanoscratch 537:547 arg1 test 549:552 a novel nanoscratch test 529:552 a novel nanoscratch test 529:552 To test the hypothesis, we used a novel nanoscratch test to measure the in situ toughness of human cadaveric bone treated with and without peptide-N-glycosidase F (PNGase F), an enzyme that specifically removes the N-linked oligosaccharides of GAGs from core proteins. 26709950 9 56 theme bone 1526:1529 arg1 toughness 1513:1521 the in situ toughness 1501:1521 the in situ toughness of bone 1501:1529 The results of this study, for the first time, suggest that GAGs play a pivotal role in the in situ toughness of bone only when water is present, and vice versa, water functions as a plasticizer in bone only when GAGs are present. 26709950 6 57 theme coupling 1103:1110 arg1 effect 1112:1117 the coupling effect 1099:1117 the coupling effect between water and PGs on the in situ toughness of bone 1099:1172 Biochemical and histochemical assays were used to verify whether N-linked oligosaccharides were removed from bone matrix by PNGase F. By testing wet and dehydrated bone specimens, the coupling effect between water and PGs on the in situ toughness of bone was investigated. 26709950 4 58 theme cadaveric 596:604 arg1 bone 606:609 human cadaveric bone 590:609 human cadaveric bone treated with and without peptide-N-glycosidase F (PNGase F), an enzyme that specifically removes the N-linked oligosaccharides of GAGs from core proteins 590:763 To test the hypothesis, we used a novel nanoscratch test to measure the in situ toughness of human cadaveric bone treated with and without peptide-N-glycosidase F (PNGase F), an enzyme that specifically removes the N-linked oligosaccharides of GAGs from core proteins. 26709950 6 59 from effect 1112:1117 arg1 toughness 1156:1164 the in situ toughness 1144:1164 the in situ toughness of bone 1144:1172 Biochemical and histochemical assays were used to verify whether N-linked oligosaccharides were removed from bone matrix by PNGase F. By testing wet and dehydrated bone specimens, the coupling effect between water and PGs on the in situ toughness of bone was investigated. 26709950 4 60 dep in 569:570 arg1 situ 572:575 situ 572:575 situ 572:575 To test the hypothesis, we used a novel nanoscratch test to measure the in situ toughness of human cadaveric bone treated with and without peptide-N-glycosidase F (PNGase F), an enzyme that specifically removes the N-linked oligosaccharides of GAGs from core proteins. 26709950 5 61 theme posterior 813:821 arg1 aspect 823:828 the posterior aspect 809:828 the posterior aspect of mid-diaphyseal femurs of six (n = 6) male human donors between 51.5 ± 5.17 years old 809:916 Cortical bone specimens were prepared from the posterior aspect of mid-diaphyseal femurs of six (n = 6) male human donors between 51.5 ± 5.17 years old. 26709950 1 62 from matrix 158:163 arg1 Proteoglycans 77:89 Proteoglycans 77:89 Proteoglycans (PGs) 77:95 Proteoglycans (PGs) are one type of noncollagenous proteins in the extracellular matrix of bone that primarily contain a core protein and glycosaminoglycans (GAGs). 26709950 1 62 from matrix 158:163 arg1 type 105:108 one type 101:108 one type of noncollagenous proteins in the extracellular matrix of bone that primarily contain a core protein and glycosaminoglycans (GAGs) 101:239 Proteoglycans (PGs) are one type of noncollagenous proteins in the extracellular matrix of bone that primarily contain a core protein and glycosaminoglycans (GAGs). 26709950 5 63 theme bone 775:778 arg1 specimens 780:788 Cortical bone specimens 766:788 Cortical bone specimens 766:788 Cortical bone specimens were prepared from the posterior aspect of mid-diaphyseal femurs of six (n = 6) male human donors between 51.5 ± 5.17 years old. 26709950 6 64 theme bone 1083:1086 arg1 specimens 1088:1096 wet and dehydrated bone specimens 1064:1096 wet and dehydrated bone specimens 1064:1096 Biochemical and histochemical assays were used to verify whether N-linked oligosaccharides were removed from bone matrix by PNGase F. By testing wet and dehydrated bone specimens, the coupling effect between water and PGs on the in situ toughness of bone was investigated. 26709950 1 65 theme noncollagenous 113:126 arg1 proteins 128:135 noncollagenous proteins 113:135 noncollagenous proteins in the extracellular matrix of bone 113:171 Proteoglycans (PGs) are one type of noncollagenous proteins in the extracellular matrix of bone that primarily contain a core protein and glycosaminoglycans (GAGs). 26709950 0 66 from Effect 9:14 arg1 Toughness 58:66 the In Situ Toughness 46:66 the In Situ Toughness of Bone 46:74 Coupling Effect of Water and Proteoglycans on the In Situ Toughness of Bone. 26709950 2 67 contain have 293:296 arg1 GAGs 242:245 GAGs 242:245 GAGs 242:245 GAGs are highly polar and negatively charged, thus have a strong tendency to attract water molecules into the matrix. 26709950 2 67 contain have 293:296 arg2 tendency 307:314 a strong tendency 298:314 a strong tendency to attract water molecules into the matrix 298:357 GAGs are highly polar and negatively charged, thus have a strong tendency to attract water molecules into the matrix. 26709950 1 68 from proteins 128:135 arg1 matrix 158:163 the extracellular matrix 140:163 the extracellular matrix of bone 140:171 Proteoglycans (PGs) are one type of noncollagenous proteins in the extracellular matrix of bone that primarily contain a core protein and glycosaminoglycans (GAGs). 26709950 4 69 link N-linked 712:719 arg1 oligosaccharides 721:736 the N-linked oligosaccharides 708:736 the N-linked oligosaccharides of GAGs from core proteins 708:763 To test the hypothesis, we used a novel nanoscratch test to measure the in situ toughness of human cadaveric bone treated with and without peptide-N-glycosidase F (PNGase F), an enzyme that specifically removes the N-linked oligosaccharides of GAGs from core proteins. 26709950 4 70 from oligosaccharides 721:736 arg1 proteins 756:763 core proteins 751:763 core proteins 751:763 To test the hypothesis, we used a novel nanoscratch test to measure the in situ toughness of human cadaveric bone treated with and without peptide-N-glycosidase F (PNGase F), an enzyme that specifically removes the N-linked oligosaccharides of GAGs from core proteins. 26709950 6 71 used used 961:964 arg2 assays 949:954 Biochemical and histochemical assays 919:954 Biochemical and histochemical assays 919:954 Biochemical and histochemical assays were used to verify whether N-linked oligosaccharides were removed from bone matrix by PNGase F. By testing wet and dehydrated bone specimens, the coupling effect between water and PGs on the in situ toughness of bone was investigated. 26709950 9 72 theme first 1448:1452 arg1 time 1454:1457 the first time 1444:1457 the first time 1444:1457 The results of this study, for the first time, suggest that GAGs play a pivotal role in the in situ toughness of bone only when water is present, and vice versa, water functions as a plasticizer in bone only when GAGs are present. 26709950 0 73 theme Water 19:23 arg1 Effect 9:14 Coupling Effect 0:14 Coupling Effect of Water and Proteoglycans on the In Situ Toughness of Bone. 0:75 Coupling Effect of Water and Proteoglycans on the In Situ Toughness of Bone. 26709950 5 74 theme femurs 848:853 arg1 aspect 823:828 the posterior aspect 809:828 the posterior aspect of mid-diaphyseal femurs of six (n = 6) male human donors between 51.5 ± 5.17 years old 809:916 Cortical bone specimens were prepared from the posterior aspect of mid-diaphyseal femurs of six (n = 6) male human donors between 51.5 ± 5.17 years old. 26709950 8 75 theme bone 1407:1410 arg1 toughness 1390:1398 the toughness 1386:1398 the toughness of dry bone 1386:1410 In contrast, the removal of GAGs did not show significant effects on the toughness of dry bone. 26709950 4 76 theme peptide-N-glycosidase 636:656 arg1 enzyme 675:680 an enzyme 672:680 an enzyme that specifically removes the N-linked oligosaccharides of GAGs from core proteins 672:763 To test the hypothesis, we used a novel nanoscratch test to measure the in situ toughness of human cadaveric bone treated with and without peptide-N-glycosidase F (PNGase F), an enzyme that specifically removes the N-linked oligosaccharides of GAGs from core proteins. 26709950 4 76 theme peptide-N-glycosidase 636:656 arg1 F 658:658 peptide-N-glycosidase F 636:658 peptide-N-glycosidase F (PNGase F) 636:669 To test the hypothesis, we used a novel nanoscratch test to measure the in situ toughness of human cadaveric bone treated with and without peptide-N-glycosidase F (PNGase F), an enzyme that specifically removes the N-linked oligosaccharides of GAGs from core proteins. 26709950 4 76 theme peptide-N-glycosidase 636:656 arg1 F 668:668 PNGase F 661:668 PNGase F 661:668 To test the hypothesis, we used a novel nanoscratch test to measure the in situ toughness of human cadaveric bone treated with and without peptide-N-glycosidase F (PNGase F), an enzyme that specifically removes the N-linked oligosaccharides of GAGs from core proteins. 26709950 0 77 theme Proteoglycans 29:41 arg1 Effect 9:14 Coupling Effect 0:14 Coupling Effect of Water and Proteoglycans on the In Situ Toughness of Bone. 0:75 Coupling Effect of Water and Proteoglycans on the In Situ Toughness of Bone. 26709950 7 78 theme ANOVA 1204:1208 arg1 analyses 1210:1217 The two-way ANOVA analyses 1192:1217 The two-way ANOVA analyses 1192:1217 The two-way ANOVA analyses showed that removal of GAGs had significant effects on the in situ toughness of wet bone samples. 26709950 8 79 from effects 1375:1381 arg1 toughness 1390:1398 the toughness 1386:1398 the toughness of dry bone 1386:1410 In contrast, the removal of GAGs did not show significant effects on the toughness of dry bone. 26709950 5 80 theme old 914:916 arg1 years 908:912 51.5 ± 5.17 years 896:912 51.5 ± 5.17 years old 896:916 Cortical bone specimens were prepared from the posterior aspect of mid-diaphyseal femurs of six (n = 6) male human donors between 51.5 ± 5.17 years old. 26709950 7 81 dep in 1278:1279 arg1 situ 1281:1284 situ 1281:1284 situ 1281:1284 The two-way ANOVA analyses showed that removal of GAGs had significant effects on the in situ toughness of wet bone samples. 26709950 6 82 link N-linked 984:991 arg1 oligosaccharides 993:1008 N-linked oligosaccharides 984:1008 N-linked oligosaccharides 984:1008 Biochemical and histochemical assays were used to verify whether N-linked oligosaccharides were removed from bone matrix by PNGase F. By testing wet and dehydrated bone specimens, the coupling effect between water and PGs on the in situ toughness of bone was investigated. 26709950 5 83 theme male 870:873 arg1 donors 881:886 six (n = 6) male human donors 858:886 six (n = 6) male human donors 858:886 Cortical bone specimens were prepared from the posterior aspect of mid-diaphyseal femurs of six (n = 6) male human donors between 51.5 ± 5.17 years old. 26709950 10 84 dep © 1644:1644 arg1 Society 1660:1666 Society 1660:1666 Society 1660:1666 © 2015 American Society for Bone and Mineral Research. 26709950 6 85 attach removed 1015:1021 arg1 matrix 1033:1038 bone matrix 1028:1038 bone matrix 1028:1038 Biochemical and histochemical assays were used to verify whether N-linked oligosaccharides were removed from bone matrix by PNGase F. By testing wet and dehydrated bone specimens, the coupling effect between water and PGs on the in situ toughness of bone was investigated. 26709950 6 85 attach removed 1015:1021 arg2 oligosaccharides 993:1008 N-linked oligosaccharides 984:1008 N-linked oligosaccharides 984:1008 Biochemical and histochemical assays were used to verify whether N-linked oligosaccharides were removed from bone matrix by PNGase F. By testing wet and dehydrated bone specimens, the coupling effect between water and PGs on the in situ toughness of bone was investigated. 26709950 5 86 theme donors 881:886 arg1 femurs 848:853 mid-diaphyseal femurs 833:853 mid-diaphyseal femurs of six (n = 6) male human donors 833:886 Cortical bone specimens were prepared from the posterior aspect of mid-diaphyseal femurs of six (n = 6) male human donors between 51.5 ± 5.17 years old. 25502804 0 0 theme receptor 77:84 arg1 expression 109:118 peptide-1 receptor (hGLP-1R) cell surface expression 67:118 peptide-1 receptor (hGLP-1R) cell surface expression 67:118 The regions within the N-terminus critical for human glucagon like peptide-1 receptor (hGLP-1R) cell surface expression. 25502804 2 1 contain contains 263:270 arg2 SP 302:303 SP 302:303 SP 302:303 Like other class B GPCRs, the GLP-1R contains an N-terminal signal peptide (SP) and undergoes N-linked glycosylation, which are important for its trafficking and maturation. 25502804 2 1 contain contains 263:270 arg1 GLP-1R 256:261 the GLP-1R 252:261 the GLP-1R 252:261 Like other class B GPCRs, the GLP-1R contains an N-terminal signal peptide (SP) and undergoes N-linked glycosylation, which are important for its trafficking and maturation. 25502804 2 1 contain contains 263:270 arg2 peptide 293:299 an N-terminal signal peptide 272:299 an N-terminal signal peptide (SP) 272:304 Like other class B GPCRs, the GLP-1R contains an N-terminal signal peptide (SP) and undergoes N-linked glycosylation, which are important for its trafficking and maturation. 25502804 1 2 theme B 207:207 arg1 family 209:214 the class B family 197:214 the class B family of GPCRs 197:223 The hGLP-1R is a target for the treatment of type 2 diabetes and belongs to the class B family of GPCRs. 25502804 0 3 theme peptide-1 67:75 arg1 hGLP-1R 87:93 hGLP-1R 87:93 hGLP-1R 87:93 The regions within the N-terminus critical for human glucagon like peptide-1 receptor (hGLP-1R) cell surface expression. 25502804 0 3 theme peptide-1 67:75 arg1 receptor 77:84 peptide-1 receptor 67:84 peptide-1 receptor (hGLP-1R) cell surface expression 67:118 The regions within the N-terminus critical for human glucagon like peptide-1 receptor (hGLP-1R) cell surface expression. 25502804 2 4 theme signal 286:291 arg1 peptide 293:299 an N-terminal signal peptide 272:299 an N-terminal signal peptide (SP) 272:304 Like other class B GPCRs, the GLP-1R contains an N-terminal signal peptide (SP) and undergoes N-linked glycosylation, which are important for its trafficking and maturation. 25502804 2 4 theme signal 286:291 arg1 SP 302:303 SP 302:303 SP 302:303 Like other class B GPCRs, the GLP-1R contains an N-terminal signal peptide (SP) and undergoes N-linked glycosylation, which are important for its trafficking and maturation. 25502804 4 5 theme cell 783:786 arg1 expression 796:805 hGLP-1R cell surface expression 775:805 hGLP-1R cell surface expression 775:805 HGLP-1R targeted to the cell surface showed no SP, and the SP deleted mutant, but not the mutants defective in SP cleavage, showed cell surface expression, demonstrating the importance of SP cleavage for hGLP-1R cell surface expression. 25502804 2 6 gly glycosylation 329:341 arg1 GLP-1R 256:261 the GLP-1R 252:261 the GLP-1R 252:261 Like other class B GPCRs, the GLP-1R contains an N-terminal signal peptide (SP) and undergoes N-linked glycosylation, which are important for its trafficking and maturation. 25502804 9 7 theme receptor 1402:1409 arg1 expression 1424:1433 the receptor cell surface expression 1398:1433 the receptor cell surface expression 1398:1433 Therefore this study provides insight into the role of hGLP-1R N-terminus on the receptor cell surface expression. 25502804 2 8 theme class 237:241 arg1 GPCRs 245:249 other class B GPCRs 231:249 other class B GPCRs 231:249 Like other class B GPCRs, the GLP-1R contains an N-terminal signal peptide (SP) and undergoes N-linked glycosylation, which are important for its trafficking and maturation. 25502804 4 9 theme SP 630:631 arg1 mutant 641:646 the SP deleted mutant 626:646 the SP deleted mutant 626:646 HGLP-1R targeted to the cell surface showed no SP, and the SP deleted mutant, but not the mutants defective in SP cleavage, showed cell surface expression, demonstrating the importance of SP cleavage for hGLP-1R cell surface expression. 25502804 3 10 from N-terminus 537:546 arg1 trafficking 558:568 GLP-1R trafficking 551:568 GLP-1R trafficking 551:568 This study analysed the role of the SP, the hydrophobic region after the SP (HRASP), glycosylation and the conserved residues within the N-terminus in GLP-1R trafficking. 25502804 9 11 theme N-terminus 1384:1393 arg1 role 1368:1371 the role 1364:1371 the role of hGLP-1R N-terminus on the receptor cell surface expression 1364:1433 Therefore this study provides insight into the role of hGLP-1R N-terminus on the receptor cell surface expression. 25502804 7 12 link N-linked 1209:1216 arg1 glycosylation 1218:1230 N-linked glycosylation 1209:1230 N-linked glycosylation 1209:1230 Mutation of Trp(39), Tyr(69) and Tyr(88), which are required for agonist binding, in the GLP-1R abolished cell surface expression of the receptor independent of the SP cleavage or N-linked glycosylation. 25502804 2 13 theme other 231:235 arg1 GPCRs 245:249 other class B GPCRs 231:249 other class B GPCRs 231:249 Like other class B GPCRs, the GLP-1R contains an N-terminal signal peptide (SP) and undergoes N-linked glycosylation, which are important for its trafficking and maturation. 25502804 1 14 theme GPCRs 219:223 arg1 family 209:214 the class B family 197:214 the class B family of GPCRs 197:223 The hGLP-1R is a target for the treatment of type 2 diabetes and belongs to the class B family of GPCRs. 25502804 0 15 theme cell 96:99 arg1 expression 109:118 peptide-1 receptor (hGLP-1R) cell surface expression 67:118 peptide-1 receptor (hGLP-1R) cell surface expression 67:118 The regions within the N-terminus critical for human glucagon like peptide-1 receptor (hGLP-1R) cell surface expression. 25502804 6 16 theme surface 993:999 arg1 expression 1001:1010 cell surface expression 988:1010 cell surface expression of the receptor 988:1026 Further, inhibition of hGLP-1R glycosylation prevented cell surface expression of the receptor. 25502804 4 17 theme surface 707:713 arg1 expression 715:724 cell surface expression 702:724 cell surface expression 702:724 HGLP-1R targeted to the cell surface showed no SP, and the SP deleted mutant, but not the mutants defective in SP cleavage, showed cell surface expression, demonstrating the importance of SP cleavage for hGLP-1R cell surface expression. 25502804 2 18 theme N-linked 320:327 arg1 glycosylation 329:341 N-linked glycosylation 320:341 N-linked glycosylation 320:341 Like other class B GPCRs, the GLP-1R contains an N-terminal signal peptide (SP) and undergoes N-linked glycosylation, which are important for its trafficking and maturation. 25502804 4 19 theme cell 702:705 arg1 expression 715:724 cell surface expression 702:724 cell surface expression 702:724 HGLP-1R targeted to the cell surface showed no SP, and the SP deleted mutant, but not the mutants defective in SP cleavage, showed cell surface expression, demonstrating the importance of SP cleavage for hGLP-1R cell surface expression. 25502804 9 20 theme surface 1416:1422 arg1 expression 1424:1433 the receptor cell surface expression 1398:1433 the receptor cell surface expression 1398:1433 Therefore this study provides insight into the role of hGLP-1R N-terminus on the receptor cell surface expression. 25502804 3 21 theme hydrophobic 444:454 arg1 region 456:461 the hydrophobic region 440:461 the hydrophobic region after the SP (HRASP) 440:482 This study analysed the role of the SP, the hydrophobic region after the SP (HRASP), glycosylation and the conserved residues within the N-terminus in GLP-1R trafficking. 25502804 7 22 theme SP 1194:1195 arg1 cleavage 1197:1204 the SP cleavage 1190:1204 the SP cleavage 1190:1204 Mutation of Trp(39), Tyr(69) and Tyr(88), which are required for agonist binding, in the GLP-1R abolished cell surface expression of the receptor independent of the SP cleavage or N-linked glycosylation. 25502804 6 23 theme receptor 1019:1026 arg1 expression 1001:1010 cell surface expression 988:1010 cell surface expression of the receptor 988:1026 Further, inhibition of hGLP-1R glycosylation prevented cell surface expression of the receptor. 25502804 7 24 from Mutation 1029:1036 arg1 GLP-1R 1118:1123 the GLP-1R 1114:1123 the GLP-1R 1114:1123 Mutation of Trp(39), Tyr(69) and Tyr(88), which are required for agonist binding, in the GLP-1R abolished cell surface expression of the receptor independent of the SP cleavage or N-linked glycosylation. 25502804 7 25 theme Trp 1041:1043 arg1 Mutation 1029:1036 Mutation 1029:1036 Mutation 1029:1036 Mutation of Trp(39), Tyr(69) and Tyr(88), which are required for agonist binding, in the GLP-1R abolished cell surface expression of the receptor independent of the SP cleavage or N-linked glycosylation. 25502804 7 26 theme glycosylation 1218:1230 arg1 independent 1175:1185 independent 1175:1185 independent 1175:1185 Mutation of Trp(39), Tyr(69) and Tyr(88), which are required for agonist binding, in the GLP-1R abolished cell surface expression of the receptor independent of the SP cleavage or N-linked glycosylation. 25502804 5 27 theme N-terminal 812:821 arg1 deletions 823:831 The N-terminal deletions 808:831 The N-terminal deletions of hGLP-1R 808:842 The N-terminal deletions of hGLP-1R revealed that the HRASP, not the SP, is essential for cell surface expression of GLP-1R. 25502804 4 28 theme cell 595:598 arg1 surface 600:606 the cell surface 591:606 the cell surface 591:606 HGLP-1R targeted to the cell surface showed no SP, and the SP deleted mutant, but not the mutants defective in SP cleavage, showed cell surface expression, demonstrating the importance of SP cleavage for hGLP-1R cell surface expression. 25502804 4 29 theme surface 788:794 arg1 expression 796:805 hGLP-1R cell surface expression 775:805 hGLP-1R cell surface expression 775:805 HGLP-1R targeted to the cell surface showed no SP, and the SP deleted mutant, but not the mutants defective in SP cleavage, showed cell surface expression, demonstrating the importance of SP cleavage for hGLP-1R cell surface expression. 25502804 7 30 theme cell 1135:1138 arg1 expression 1148:1157 cell surface expression 1135:1157 cell surface expression of the receptor independent of the SP cleavage or N-linked glycosylation 1135:1230 Mutation of Trp(39), Tyr(69) and Tyr(88), which are required for agonist binding, in the GLP-1R abolished cell surface expression of the receptor independent of the SP cleavage or N-linked glycosylation. 25502804 4 31 theme deleted 633:639 arg1 mutant 641:646 the SP deleted mutant 626:646 the SP deleted mutant 626:646 HGLP-1R targeted to the cell surface showed no SP, and the SP deleted mutant, but not the mutants defective in SP cleavage, showed cell surface expression, demonstrating the importance of SP cleavage for hGLP-1R cell surface expression. 25502804 1 32 theme type 166:169 arg1 diabetes 173:180 type 2 diabetes 166:180 type 2 diabetes 166:180 The hGLP-1R is a target for the treatment of type 2 diabetes and belongs to the class B family of GPCRs. 25502804 7 33 theme cleavage 1197:1204 arg1 independent 1175:1185 independent 1175:1185 independent 1175:1185 Mutation of Trp(39), Tyr(69) and Tyr(88), which are required for agonist binding, in the GLP-1R abolished cell surface expression of the receptor independent of the SP cleavage or N-linked glycosylation. 25502804 0 34 theme surface 101:107 arg1 expression 109:118 peptide-1 receptor (hGLP-1R) cell surface expression 67:118 peptide-1 receptor (hGLP-1R) cell surface expression 67:118 The regions within the N-terminus critical for human glucagon like peptide-1 receptor (hGLP-1R) cell surface expression. 25502804 2 35 theme B 243:243 arg1 GPCRs 245:249 other class B GPCRs 231:249 other class B GPCRs 231:249 Like other class B GPCRs, the GLP-1R contains an N-terminal signal peptide (SP) and undergoes N-linked glycosylation, which are important for its trafficking and maturation. 25502804 3 36 gly glycosylation 485:497 arg1 SP 436:437 the SP 432:437 the SP 432:437 This study analysed the role of the SP, the hydrophobic region after the SP (HRASP), glycosylation and the conserved residues within the N-terminus in GLP-1R trafficking. 25502804 0 37 theme critical 34:41 arg1 N-terminus 23:32 the N-terminus 19:32 the N-terminus critical for human glucagon like peptide-1 receptor (hGLP-1R) cell surface expression 19:118 The regions within the N-terminus critical for human glucagon like peptide-1 receptor (hGLP-1R) cell surface expression. 25502804 3 38 theme GLP-1R 551:556 arg1 trafficking 558:568 GLP-1R trafficking 551:568 GLP-1R trafficking 551:568 This study analysed the role of the SP, the hydrophobic region after the SP (HRASP), glycosylation and the conserved residues within the N-terminus in GLP-1R trafficking. 25502804 7 39 theme receptor 1166:1173 arg1 expression 1148:1157 cell surface expression 1135:1157 cell surface expression of the receptor independent of the SP cleavage or N-linked glycosylation 1135:1230 Mutation of Trp(39), Tyr(69) and Tyr(88), which are required for agonist binding, in the GLP-1R abolished cell surface expression of the receptor independent of the SP cleavage or N-linked glycosylation. 25502804 1 40 theme diabetes 173:180 arg1 treatment 153:161 the treatment 149:161 the treatment of type 2 diabetes 149:180 The hGLP-1R is a target for the treatment of type 2 diabetes and belongs to the class B family of GPCRs. 25502804 7 41 theme Tyr 1050:1052 arg1 Mutation 1029:1036 Mutation 1029:1036 Mutation 1029:1036 Mutation of Trp(39), Tyr(69) and Tyr(88), which are required for agonist binding, in the GLP-1R abolished cell surface expression of the receptor independent of the SP cleavage or N-linked glycosylation. 25502804 2 42 link N-linked 320:327 arg1 glycosylation 329:341 N-linked glycosylation 320:341 N-linked glycosylation 320:341 Like other class B GPCRs, the GLP-1R contains an N-terminal signal peptide (SP) and undergoes N-linked glycosylation, which are important for its trafficking and maturation. 25502804 4 43 theme SP 682:683 arg1 cleavage 685:692 SP cleavage 682:692 SP cleavage 682:692 HGLP-1R targeted to the cell surface showed no SP, and the SP deleted mutant, but not the mutants defective in SP cleavage, showed cell surface expression, demonstrating the importance of SP cleavage for hGLP-1R cell surface expression. 25502804 7 44 theme Tyr 1062:1064 arg1 Mutation 1029:1036 Mutation 1029:1036 Mutation 1029:1036 Mutation of Trp(39), Tyr(69) and Tyr(88), which are required for agonist binding, in the GLP-1R abolished cell surface expression of the receptor independent of the SP cleavage or N-linked glycosylation. 25502804 0 45 theme human 47:51 arg1 glucagon 53:60 human glucagon 47:60 human glucagon like peptide-1 receptor (hGLP-1R) cell surface expression 47:118 The regions within the N-terminus critical for human glucagon like peptide-1 receptor (hGLP-1R) cell surface expression. 25502804 4 46 theme cleavage 762:769 arg1 importance 745:754 the importance 741:754 the importance of SP cleavage for hGLP-1R cell surface expression 741:805 HGLP-1R targeted to the cell surface showed no SP, and the SP deleted mutant, but not the mutants defective in SP cleavage, showed cell surface expression, demonstrating the importance of SP cleavage for hGLP-1R cell surface expression. 25502804 8 47 theme receptor 1284:1291 arg1 trafficking 1293:1303 receptor trafficking 1284:1303 receptor trafficking 1284:1303 In conclusion, the N-terminus of hGLP-1R regulates receptor trafficking and maturation. 25502804 6 48 theme hGLP-1R 956:962 arg1 glycosylation 964:976 hGLP-1R glycosylation 956:976 hGLP-1R glycosylation 956:976 Further, inhibition of hGLP-1R glycosylation prevented cell surface expression of the receptor. 25502804 2 49 theme N-terminal 275:284 arg1 peptide 293:299 an N-terminal signal peptide 272:299 an N-terminal signal peptide (SP) 272:304 Like other class B GPCRs, the GLP-1R contains an N-terminal signal peptide (SP) and undergoes N-linked glycosylation, which are important for its trafficking and maturation. 25502804 2 49 theme N-terminal 275:284 arg1 SP 302:303 SP 302:303 SP 302:303 Like other class B GPCRs, the GLP-1R contains an N-terminal signal peptide (SP) and undergoes N-linked glycosylation, which are important for its trafficking and maturation. 25502804 4 50 theme SP 759:760 arg1 cleavage 762:769 SP cleavage 759:769 SP cleavage 759:769 HGLP-1R targeted to the cell surface showed no SP, and the SP deleted mutant, but not the mutants defective in SP cleavage, showed cell surface expression, demonstrating the importance of SP cleavage for hGLP-1R cell surface expression. 25502804 9 51 theme cell 1411:1414 arg1 expression 1424:1433 the receptor cell surface expression 1398:1433 the receptor cell surface expression 1398:1433 Therefore this study provides insight into the role of hGLP-1R N-terminus on the receptor cell surface expression. 25502804 4 52 from cleavage 685:692 arg1 defective 669:677 defective 669:677 defective 669:677 HGLP-1R targeted to the cell surface showed no SP, and the SP deleted mutant, but not the mutants defective in SP cleavage, showed cell surface expression, demonstrating the importance of SP cleavage for hGLP-1R cell surface expression. 25502804 6 53 theme cell 988:991 arg1 expression 1001:1010 cell surface expression 988:1010 cell surface expression of the receptor 988:1026 Further, inhibition of hGLP-1R glycosylation prevented cell surface expression of the receptor. 25502804 4 54 theme defective 669:677 arg1 mutants 661:667 the mutants 657:667 the mutants defective in SP cleavage 657:692 HGLP-1R targeted to the cell surface showed no SP, and the SP deleted mutant, but not the mutants defective in SP cleavage, showed cell surface expression, demonstrating the importance of SP cleavage for hGLP-1R cell surface expression. 25502804 4 55 theme hGLP-1R 775:781 arg1 expression 796:805 hGLP-1R cell surface expression 775:805 hGLP-1R cell surface expression 775:805 HGLP-1R targeted to the cell surface showed no SP, and the SP deleted mutant, but not the mutants defective in SP cleavage, showed cell surface expression, demonstrating the importance of SP cleavage for hGLP-1R cell surface expression. 25502804 5 56 theme cell 898:901 arg1 expression 911:920 cell surface expression 898:920 cell surface expression of GLP-1R 898:930 The N-terminal deletions of hGLP-1R revealed that the HRASP, not the SP, is essential for cell surface expression of GLP-1R. 25502804 7 57 theme surface 1140:1146 arg1 expression 1148:1157 cell surface expression 1135:1157 cell surface expression of the receptor independent of the SP cleavage or N-linked glycosylation 1135:1230 Mutation of Trp(39), Tyr(69) and Tyr(88), which are required for agonist binding, in the GLP-1R abolished cell surface expression of the receptor independent of the SP cleavage or N-linked glycosylation. 25502804 7 58 theme independent 1175:1185 arg1 receptor 1166:1173 the receptor 1162:1173 the receptor independent of the SP cleavage or N-linked glycosylation 1162:1230 Mutation of Trp(39), Tyr(69) and Tyr(88), which are required for agonist binding, in the GLP-1R abolished cell surface expression of the receptor independent of the SP cleavage or N-linked glycosylation. 25502804 9 59 theme hGLP-1R 1376:1382 arg1 N-terminus 1384:1393 hGLP-1R N-terminus 1376:1393 hGLP-1R N-terminus 1376:1393 Therefore this study provides insight into the role of hGLP-1R N-terminus on the receptor cell surface expression. 25502804 7 60 theme N-linked 1209:1216 arg1 glycosylation 1218:1230 N-linked glycosylation 1209:1230 N-linked glycosylation 1209:1230 Mutation of Trp(39), Tyr(69) and Tyr(88), which are required for agonist binding, in the GLP-1R abolished cell surface expression of the receptor independent of the SP cleavage or N-linked glycosylation. 25502804 5 61 theme surface 903:909 arg1 expression 911:920 cell surface expression 898:920 cell surface expression of GLP-1R 898:930 The N-terminal deletions of hGLP-1R revealed that the HRASP, not the SP, is essential for cell surface expression of GLP-1R. 25502804 5 62 theme hGLP-1R 836:842 arg1 deletions 823:831 The N-terminal deletions 808:831 The N-terminal deletions of hGLP-1R 808:842 The N-terminal deletions of hGLP-1R revealed that the HRASP, not the SP, is essential for cell surface expression of GLP-1R. 25502804 5 63 theme GLP-1R 925:930 arg1 expression 911:920 cell surface expression 898:920 cell surface expression of GLP-1R 898:930 The N-terminal deletions of hGLP-1R revealed that the HRASP, not the SP, is essential for cell surface expression of GLP-1R. 25502804 6 64 theme glycosylation 964:976 arg1 inhibition 942:951 inhibition 942:951 inhibition of hGLP-1R glycosylation 942:976 Further, inhibition of hGLP-1R glycosylation prevented cell surface expression of the receptor. 25502804 9 65 from role 1368:1371 arg1 expression 1424:1433 the receptor cell surface expression 1398:1433 the receptor cell surface expression 1398:1433 Therefore this study provides insight into the role of hGLP-1R N-terminus on the receptor cell surface expression. 25502804 8 66 theme hGLP-1R 1266:1272 arg1 N-terminus 1252:1261 the N-terminus 1248:1261 the N-terminus of hGLP-1R 1248:1272 In conclusion, the N-terminus of hGLP-1R regulates receptor trafficking and maturation. 25502804 4 67 from defective 669:677 arg1 cleavage 685:692 SP cleavage 682:692 SP cleavage 682:692 HGLP-1R targeted to the cell surface showed no SP, and the SP deleted mutant, but not the mutants defective in SP cleavage, showed cell surface expression, demonstrating the importance of SP cleavage for hGLP-1R cell surface expression. 25502804 3 68 theme SP 436:437 arg1 region 456:461 the hydrophobic region 440:461 the hydrophobic region after the SP (HRASP) 440:482 This study analysed the role of the SP, the hydrophobic region after the SP (HRASP), glycosylation and the conserved residues within the N-terminus in GLP-1R trafficking. 25502804 3 68 theme SP 436:437 arg1 glycosylation 485:497 glycosylation 485:497 glycosylation 485:497 This study analysed the role of the SP, the hydrophobic region after the SP (HRASP), glycosylation and the conserved residues within the N-terminus in GLP-1R trafficking. 25502804 3 68 theme SP 436:437 arg1 role 424:427 the role 420:427 the role of the SP 420:437 This study analysed the role of the SP, the hydrophobic region after the SP (HRASP), glycosylation and the conserved residues within the N-terminus in GLP-1R trafficking. 25502804 3 68 theme SP 436:437 arg1 residues 517:524 the conserved residues 503:524 the conserved residues within the N-terminus in GLP-1R trafficking 503:568 This study analysed the role of the SP, the hydrophobic region after the SP (HRASP), glycosylation and the conserved residues within the N-terminus in GLP-1R trafficking. 25502804 3 68 theme SP 436:437 arg1 SP 436:437 the SP 432:437 the SP 432:437 This study analysed the role of the SP, the hydrophobic region after the SP (HRASP), glycosylation and the conserved residues within the N-terminus in GLP-1R trafficking. 25502804 7 69 theme agonist 1094:1100 arg1 binding 1102:1108 agonist binding 1094:1108 agonist binding 1094:1108 Mutation of Trp(39), Tyr(69) and Tyr(88), which are required for agonist binding, in the GLP-1R abolished cell surface expression of the receptor independent of the SP cleavage or N-linked glycosylation. 25502804 3 70 theme conserved 507:515 arg1 SP 436:437 the SP 432:437 the SP 432:437 This study analysed the role of the SP, the hydrophobic region after the SP (HRASP), glycosylation and the conserved residues within the N-terminus in GLP-1R trafficking. 25502804 3 70 theme conserved 507:515 arg1 residues 517:524 the conserved residues 503:524 the conserved residues within the N-terminus in GLP-1R trafficking 503:568 This study analysed the role of the SP, the hydrophobic region after the SP (HRASP), glycosylation and the conserved residues within the N-terminus in GLP-1R trafficking. 25502804 1 71 theme class 201:205 arg1 family 209:214 the class B family 197:214 the class B family of GPCRs 197:223 The hGLP-1R is a target for the treatment of type 2 diabetes and belongs to the class B family of GPCRs. 28126620 0 0 theme intracellular 63:75 arg1 cytokine 87:94 an intracellular antiviral cytokine 60:94 an intracellular antiviral cytokine against SVCV and GCRV 60:116 IFNa2 of triploid hybrid of gold fish and allotetraploid is an intracellular antiviral cytokine against SVCV and GCRV. 28126620 0 0 theme intracellular 63:75 arg1 IFNa2 0:4 IFNa2 0:4 IFNa2 of triploid hybrid of gold fish and allotetraploid 0:55 IFNa2 of triploid hybrid of gold fish and allotetraploid is an intracellular antiviral cytokine against SVCV and GCRV. 28126620 9 1 theme host 1645:1648 arg1 immunity 1667:1674 host antiviral innate immunity 1645:1674 host antiviral innate immunity 1645:1674 All the above data support the conclusion that 3nIFNa2 is an intracellular cytokine functioning importantly in host antiviral innate immunity. 28126620 6 2 theme control 1153:1159 arg1 cells 1161:1165 the control cells 1149:1165 the control cells 1149:1165 EPC cells transfected with plasmid expressing 3nIFNa2 at 24 h before SVCV and GCRV infection showed obviously decreased cytopathic effect; and the virus titers in the supernatant media were much lower than those of the control cells. 28126620 3 3 theme 3nIFNa2 507:513 arg1 gene 515:518 3nIFNa2 gene 507:518 3nIFNa2 gene 507:518 The full-length cDNA of 3nIFNa2 gene consists of 715 nucleotides and the predicted 3nIFNa2 contains 183 amino acids. 28126620 7 4 theme N-linked 1242:1249 arg1 glycosylation 1251:1263 N-linked glycosylation 1242:1263 N-linked glycosylation 1242:1263 Glycosidase digestion analysis demonstrates that 3nIFNa2 is modified with N-linked glycosylation, which occurs on the asparagine (N) of residue 177 of this cytokine. 28126620 5 5 located detected 804:811 arg2 3nIFNa2 787:793 3nIFNa2 787:793 3nIFNa2 787:793 3nIFNa2 has been detected in the whole cell lysate of HEK293T cells transfected with plasmids expressing 3nIFNa2 but not in the supernatant media. 28126620 5 5 located detected 804:811 arg1 lysate 831:836 the whole cell lysate 816:836 the whole cell lysate of HEK293T cells transfected with plasmids expressing 3nIFNa2 but not in the supernatant media 816:931 3nIFNa2 has been detected in the whole cell lysate of HEK293T cells transfected with plasmids expressing 3nIFNa2 but not in the supernatant media. 28126620 6 6 from titers 1087:1092 arg1 media 1113:1117 the supernatant media 1097:1117 the supernatant media 1097:1117 EPC cells transfected with plasmid expressing 3nIFNa2 at 24 h before SVCV and GCRV infection showed obviously decreased cytopathic effect; and the virus titers in the supernatant media were much lower than those of the control cells. 28126620 2 7 theme hybrid 431:436 arg1 IFNs 414:417 the type I IFNs 403:417 the type I IFNs of triploid hybrid (3nIFNa2) 403:446 In this paper, one of the type I IFNs of triploid hybrid (3nIFNa2) has been cloned and characterized. 28126620 3 8 theme amino 587:591 arg1 acids 593:597 183 amino acids 583:597 183 amino acids 583:597 The full-length cDNA of 3nIFNa2 gene consists of 715 nucleotides and the predicted 3nIFNa2 contains 183 amino acids. 28126620 7 9 mod modified 1228:1235 arg3 glycosylation 1251:1263 N-linked glycosylation 1242:1263 N-linked glycosylation 1242:1263 Glycosidase digestion analysis demonstrates that 3nIFNa2 is modified with N-linked glycosylation, which occurs on the asparagine (N) of residue 177 of this cytokine. 28126620 7 9 mod modified 1228:1235 arg1 3nIFNa2 1217:1223 3nIFNa2 1217:1223 3nIFNa2 1217:1223 Glycosidase digestion analysis demonstrates that 3nIFNa2 is modified with N-linked glycosylation, which occurs on the asparagine (N) of residue 177 of this cytokine. 28126620 6 10 theme GCRV 1012:1015 arg1 infection 1017:1025 GCRV infection 1012:1025 GCRV infection 1012:1025 EPC cells transfected with plasmid expressing 3nIFNa2 at 24 h before SVCV and GCRV infection showed obviously decreased cytopathic effect; and the virus titers in the supernatant media were much lower than those of the control cells. 28126620 8 11 theme antiviral 1514:1522 arg1 property 1524:1531 its antiviral property 1510:1531 its antiviral property 1510:1531 The un-glycosylated mutant 3nIFNa2-N177Q shows the similar antiviral ability as that of 3nIFNa2, which suggests that the N-linked glycosylation does not contribute directly to its antiviral property. 28126620 0 12 theme antiviral 77:85 arg1 cytokine 87:94 an intracellular antiviral cytokine 60:94 an intracellular antiviral cytokine against SVCV and GCRV 60:116 IFNa2 of triploid hybrid of gold fish and allotetraploid is an intracellular antiviral cytokine against SVCV and GCRV. 28126620 0 12 theme antiviral 77:85 arg1 IFNa2 0:4 IFNa2 0:4 IFNa2 of triploid hybrid of gold fish and allotetraploid 0:55 IFNa2 of triploid hybrid of gold fish and allotetraploid is an intracellular antiviral cytokine against SVCV and GCRV. 28126620 1 13 theme enhanced 298:305 arg1 rate 314:317 much enhanced growth rate 293:317 much enhanced growth rate 293:317 Sterile triploid hybrids (3n = 150) of gold fish (Carassius auratus red var., ♀, 2n = 100) and allotetroploid (♂, 2n = 100) display obviously improved disease resistance and much enhanced growth rate than their parents, which have been cultured widely in China. 28126620 7 14 theme residue 1304:1310 arg1 asparagine 1286:1295 the asparagine 1282:1295 the asparagine (N) of residue 177 of this cytokine 1282:1331 Glycosidase digestion analysis demonstrates that 3nIFNa2 is modified with N-linked glycosylation, which occurs on the asparagine (N) of residue 177 of this cytokine. 28126620 7 14 theme residue 1304:1310 arg1 N 1298:1298 N 1298:1298 N 1298:1298 Glycosidase digestion analysis demonstrates that 3nIFNa2 is modified with N-linked glycosylation, which occurs on the asparagine (N) of residue 177 of this cytokine. 28126620 1 15 theme allotetroploid 214:227 arg1 hybrids 136:142 Sterile triploid hybrids 119:142 Sterile triploid hybrids (3n = 150) of gold fish (Carassius auratus red var., ♀, 2n = 100) and allotetroploid (♂, 2n = 100) 119:241 Sterile triploid hybrids (3n = 150) of gold fish (Carassius auratus red var., ♀, 2n = 100) and allotetroploid (♂, 2n = 100) display obviously improved disease resistance and much enhanced growth rate than their parents, which have been cultured widely in China. 28126620 1 15 theme allotetroploid 214:227 arg1 3n = 150 145:152 3n = 150 145:152 3n = 150 145:152 Sterile triploid hybrids (3n = 150) of gold fish (Carassius auratus red var., ♀, 2n = 100) and allotetroploid (♂, 2n = 100) display obviously improved disease resistance and much enhanced growth rate than their parents, which have been cultured widely in China. 28126620 1 16 theme growth 307:312 arg1 rate 314:317 much enhanced growth rate 293:317 much enhanced growth rate 293:317 Sterile triploid hybrids (3n = 150) of gold fish (Carassius auratus red var., ♀, 2n = 100) and allotetroploid (♂, 2n = 100) display obviously improved disease resistance and much enhanced growth rate than their parents, which have been cultured widely in China. 28126620 9 17 theme above 1542:1546 arg1 data 1548:1551 All the above data 1534:1551 All the above data 1534:1551 All the above data support the conclusion that 3nIFNa2 is an intracellular cytokine functioning importantly in host antiviral innate immunity. 28126620 7 18 theme digestion 1180:1188 arg1 analysis 1190:1197 Glycosidase digestion analysis 1168:1197 Glycosidase digestion analysis 1168:1197 Glycosidase digestion analysis demonstrates that 3nIFNa2 is modified with N-linked glycosylation, which occurs on the asparagine (N) of residue 177 of this cytokine. 28126620 5 19 theme HEK293T 841:847 arg1 cells 849:853 HEK293T cells 841:853 HEK293T cells transfected with plasmids expressing 3nIFNa2 but not in the supernatant media 841:931 3nIFNa2 has been detected in the whole cell lysate of HEK293T cells transfected with plasmids expressing 3nIFNa2 but not in the supernatant media. 28126620 3 20 contain contains 574:581 arg1 3nIFNa2 566:572 the predicted 3nIFNa2 552:572 the predicted 3nIFNa2 552:572 The full-length cDNA of 3nIFNa2 gene consists of 715 nucleotides and the predicted 3nIFNa2 contains 183 amino acids. 28126620 3 20 contain contains 574:581 arg2 acids 593:597 183 amino acids 583:597 183 amino acids 583:597 The full-length cDNA of 3nIFNa2 gene consists of 715 nucleotides and the predicted 3nIFNa2 contains 183 amino acids. 28126620 2 21 theme IFNs 414:417 arg1 IFNs 414:417 the type I IFNs 403:417 the type I IFNs of triploid hybrid (3nIFNa2) 403:446 In this paper, one of the type I IFNs of triploid hybrid (3nIFNa2) has been cloned and characterized. 28126620 2 21 theme IFNs 414:417 arg1 one 396:398 one 396:398 one 396:398 In this paper, one of the type I IFNs of triploid hybrid (3nIFNa2) has been cloned and characterized. 28126620 4 22 theme 3nIFNa2 716:722 arg1 level 707:711 the mRNA level 698:711 the mRNA level of 3nIFNa2 698:722 The transcription of 3nIFNa2 gene was detected in all the examined tissues of triploid hybrid and the mRNA level of 3nIFNa2 was obviously enhanced in response to SVCV and GCRV infection. 28126620 4 23 theme examined 658:665 arg1 tissues 667:673 all the examined tissues 650:673 all the examined tissues of triploid hybrid 650:692 The transcription of 3nIFNa2 gene was detected in all the examined tissues of triploid hybrid and the mRNA level of 3nIFNa2 was obviously enhanced in response to SVCV and GCRV infection. 28126620 8 24 theme N-linked 1455:1462 arg1 glycosylation 1464:1476 the N-linked glycosylation 1451:1476 the N-linked glycosylation 1451:1476 The un-glycosylated mutant 3nIFNa2-N177Q shows the similar antiviral ability as that of 3nIFNa2, which suggests that the N-linked glycosylation does not contribute directly to its antiviral property. 28126620 7 25 gly glycosylation 1251:1263 arg2 N 1298:1298 N 1298:1298 N 1298:1298 Glycosidase digestion analysis demonstrates that 3nIFNa2 is modified with N-linked glycosylation, which occurs on the asparagine (N) of residue 177 of this cytokine. 28126620 7 25 gly glycosylation 1251:1263 arg2 asparagine 1286:1295 the asparagine 1282:1295 the asparagine (N) of residue 177 of this cytokine 1282:1331 Glycosidase digestion analysis demonstrates that 3nIFNa2 is modified with N-linked glycosylation, which occurs on the asparagine (N) of residue 177 of this cytokine. 28126620 9 26 theme antiviral 1650:1658 arg1 immunity 1667:1674 host antiviral innate immunity 1645:1674 host antiviral innate immunity 1645:1674 All the above data support the conclusion that 3nIFNa2 is an intracellular cytokine functioning importantly in host antiviral innate immunity. 28126620 8 27 link N-linked 1455:1462 arg1 glycosylation 1464:1476 the N-linked glycosylation 1451:1476 the N-linked glycosylation 1451:1476 The un-glycosylated mutant 3nIFNa2-N177Q shows the similar antiviral ability as that of 3nIFNa2, which suggests that the N-linked glycosylation does not contribute directly to its antiviral property. 28126620 7 28 theme cytokine 1324:1331 arg1 cytokine 1324:1331 this cytokine 1319:1331 this cytokine 1319:1331 Glycosidase digestion analysis demonstrates that 3nIFNa2 is modified with N-linked glycosylation, which occurs on the asparagine (N) of residue 177 of this cytokine. 28126620 7 28 theme cytokine 1324:1331 arg1 residue 1304:1310 residue 177 1304:1314 residue 177 of this cytokine 1304:1331 Glycosidase digestion analysis demonstrates that 3nIFNa2 is modified with N-linked glycosylation, which occurs on the asparagine (N) of residue 177 of this cytokine. 28126620 1 29 theme gold 158:161 arg1 fish 163:166 gold fish 158:166 gold fish (Carassius auratus red var., ♀, 2n = 100) 158:208 Sterile triploid hybrids (3n = 150) of gold fish (Carassius auratus red var., ♀, 2n = 100) and allotetroploid (♂, 2n = 100) display obviously improved disease resistance and much enhanced growth rate than their parents, which have been cultured widely in China. 28126620 8 30 theme similar 1385:1391 arg1 ability 1403:1409 the similar antiviral ability 1381:1409 the similar antiviral ability 1381:1409 The un-glycosylated mutant 3nIFNa2-N177Q shows the similar antiviral ability as that of 3nIFNa2, which suggests that the N-linked glycosylation does not contribute directly to its antiviral property. 28126620 8 31 theme un-glycosylated 1338:1352 arg1 3nIFNa2-N177Q 1361:1373 The un-glycosylated mutant 3nIFNa2-N177Q 1334:1373 The un-glycosylated mutant 3nIFNa2-N177Q 1334:1373 The un-glycosylated mutant 3nIFNa2-N177Q shows the similar antiviral ability as that of 3nIFNa2, which suggests that the N-linked glycosylation does not contribute directly to its antiviral property. 28126620 4 32 theme gene 629:632 arg1 transcription 604:616 The transcription 600:616 The transcription of 3nIFNa2 gene 600:632 The transcription of 3nIFNa2 gene was detected in all the examined tissues of triploid hybrid and the mRNA level of 3nIFNa2 was obviously enhanced in response to SVCV and GCRV infection. 28126620 1 33 theme fish 163:166 arg1 hybrids 136:142 Sterile triploid hybrids 119:142 Sterile triploid hybrids (3n = 150) of gold fish (Carassius auratus red var., ♀, 2n = 100) and allotetroploid (♂, 2n = 100) 119:241 Sterile triploid hybrids (3n = 150) of gold fish (Carassius auratus red var., ♀, 2n = 100) and allotetroploid (♂, 2n = 100) display obviously improved disease resistance and much enhanced growth rate than their parents, which have been cultured widely in China. 28126620 1 33 theme fish 163:166 arg1 3n = 150 145:152 3n = 150 145:152 3n = 150 145:152 Sterile triploid hybrids (3n = 150) of gold fish (Carassius auratus red var., ♀, 2n = 100) and allotetroploid (♂, 2n = 100) display obviously improved disease resistance and much enhanced growth rate than their parents, which have been cultured widely in China. 28126620 0 34 theme hybrid 18:23 arg1 cytokine 87:94 an intracellular antiviral cytokine 60:94 an intracellular antiviral cytokine against SVCV and GCRV 60:116 IFNa2 of triploid hybrid of gold fish and allotetraploid is an intracellular antiviral cytokine against SVCV and GCRV. 28126620 0 34 theme hybrid 18:23 arg1 IFNa2 0:4 IFNa2 0:4 IFNa2 of triploid hybrid of gold fish and allotetraploid 0:55 IFNa2 of triploid hybrid of gold fish and allotetraploid is an intracellular antiviral cytokine against SVCV and GCRV. 28126620 5 35 theme whole 820:824 arg1 lysate 831:836 the whole cell lysate 816:836 the whole cell lysate of HEK293T cells transfected with plasmids expressing 3nIFNa2 but not in the supernatant media 816:931 3nIFNa2 has been detected in the whole cell lysate of HEK293T cells transfected with plasmids expressing 3nIFNa2 but not in the supernatant media. 28126620 4 36 theme mRNA 702:705 arg1 level 707:711 the mRNA level 698:711 the mRNA level of 3nIFNa2 698:722 The transcription of 3nIFNa2 gene was detected in all the examined tissues of triploid hybrid and the mRNA level of 3nIFNa2 was obviously enhanced in response to SVCV and GCRV infection. 28126620 6 37 dep showed 1027:1032 arg1 decreased 1044:1052 decreased 1044:1052 showed obviously decreased cytopathic effect 1027:1070 EPC cells transfected with plasmid expressing 3nIFNa2 at 24 h before SVCV and GCRV infection showed obviously decreased cytopathic effect; and the virus titers in the supernatant media were much lower than those of the control cells. 28126620 0 38 theme triploid 9:16 arg1 hybrid 18:23 triploid hybrid 9:23 triploid hybrid of gold fish and allotetraploid 9:55 IFNa2 of triploid hybrid of gold fish and allotetraploid is an intracellular antiviral cytokine against SVCV and GCRV. 28126620 8 39 theme antiviral 1393:1401 arg1 ability 1403:1409 the similar antiviral ability 1381:1409 the similar antiviral ability 1381:1409 The un-glycosylated mutant 3nIFNa2-N177Q shows the similar antiviral ability as that of 3nIFNa2, which suggests that the N-linked glycosylation does not contribute directly to its antiviral property. 28126620 6 40 theme cytopathic 1054:1063 arg1 effect 1065:1070 cytopathic effect 1054:1070 cytopathic effect 1054:1070 EPC cells transfected with plasmid expressing 3nIFNa2 at 24 h before SVCV and GCRV infection showed obviously decreased cytopathic effect; and the virus titers in the supernatant media were much lower than those of the control cells. 28126620 5 41 theme cell 826:829 arg1 lysate 831:836 the whole cell lysate 816:836 the whole cell lysate of HEK293T cells transfected with plasmids expressing 3nIFNa2 but not in the supernatant media 816:931 3nIFNa2 has been detected in the whole cell lysate of HEK293T cells transfected with plasmids expressing 3nIFNa2 but not in the supernatant media. 28126620 1 42 theme Carassius 169:177 arg1 ♀ 197:197 ♀ 197:197 ♀ 197:197 Sterile triploid hybrids (3n = 150) of gold fish (Carassius auratus red var., ♀, 2n = 100) and allotetroploid (♂, 2n = 100) display obviously improved disease resistance and much enhanced growth rate than their parents, which have been cultured widely in China. 28126620 1 42 theme Carassius 169:177 arg1 var. 191:194 Carassius auratus red var. 169:194 Carassius auratus red var. 169:194 Sterile triploid hybrids (3n = 150) of gold fish (Carassius auratus red var., ♀, 2n = 100) and allotetroploid (♂, 2n = 100) display obviously improved disease resistance and much enhanced growth rate than their parents, which have been cultured widely in China. 28126620 1 42 theme Carassius 169:177 arg1 2n = 100 200:207 2n = 100 200:207 2n = 100 200:207 Sterile triploid hybrids (3n = 150) of gold fish (Carassius auratus red var., ♀, 2n = 100) and allotetroploid (♂, 2n = 100) display obviously improved disease resistance and much enhanced growth rate than their parents, which have been cultured widely in China. 28126620 0 43 theme gold 28:31 arg1 fish 33:36 gold fish 28:36 gold fish 28:36 IFNa2 of triploid hybrid of gold fish and allotetraploid is an intracellular antiviral cytokine against SVCV and GCRV. 28126620 1 44 theme 2n = 100 233:240 arg1 ♂ 230:230 ♂ 230:230 ♂ 230:230 Sterile triploid hybrids (3n = 150) of gold fish (Carassius auratus red var., ♀, 2n = 100) and allotetroploid (♂, 2n = 100) display obviously improved disease resistance and much enhanced growth rate than their parents, which have been cultured widely in China. 28126620 4 45 dep SVCV 762:765 arg1 response 750:757 response 750:757 response 750:757 The transcription of 3nIFNa2 gene was detected in all the examined tissues of triploid hybrid and the mRNA level of 3nIFNa2 was obviously enhanced in response to SVCV and GCRV infection. 28126620 3 46 theme full-length 487:497 arg1 cDNA 499:502 The full-length cDNA 483:502 The full-length cDNA of 3nIFNa2 gene 483:518 The full-length cDNA of 3nIFNa2 gene consists of 715 nucleotides and the predicted 3nIFNa2 contains 183 amino acids. 28126620 6 47 theme EPC 934:936 arg1 cells 938:942 EPC cells 934:942 EPC cells transfected with plasmid expressing 3nIFNa2 at 24 h before SVCV and GCRV infection 934:1025 EPC cells transfected with plasmid expressing 3nIFNa2 at 24 h before SVCV and GCRV infection showed obviously decreased cytopathic effect; and the virus titers in the supernatant media were much lower than those of the control cells. 28126620 8 48 gly un-glycosylated 1338:1352 arg1 3nIFNa2-N177Q 1361:1373 The un-glycosylated mutant 3nIFNa2-N177Q 1334:1373 The un-glycosylated mutant 3nIFNa2-N177Q 1334:1373 The un-glycosylated mutant 3nIFNa2-N177Q shows the similar antiviral ability as that of 3nIFNa2, which suggests that the N-linked glycosylation does not contribute directly to its antiviral property. 28126620 1 49 dep fish 163:166 arg1 ♀ 197:197 ♀ 197:197 ♀ 197:197 Sterile triploid hybrids (3n = 150) of gold fish (Carassius auratus red var., ♀, 2n = 100) and allotetroploid (♂, 2n = 100) display obviously improved disease resistance and much enhanced growth rate than their parents, which have been cultured widely in China. 28126620 1 49 dep fish 163:166 arg1 var. 191:194 Carassius auratus red var. 169:194 Carassius auratus red var. 169:194 Sterile triploid hybrids (3n = 150) of gold fish (Carassius auratus red var., ♀, 2n = 100) and allotetroploid (♂, 2n = 100) display obviously improved disease resistance and much enhanced growth rate than their parents, which have been cultured widely in China. 28126620 1 49 dep fish 163:166 arg1 2n = 100 200:207 2n = 100 200:207 2n = 100 200:207 Sterile triploid hybrids (3n = 150) of gold fish (Carassius auratus red var., ♀, 2n = 100) and allotetroploid (♂, 2n = 100) display obviously improved disease resistance and much enhanced growth rate than their parents, which have been cultured widely in China. 28126620 1 50 theme red 187:189 arg1 ♀ 197:197 ♀ 197:197 ♀ 197:197 Sterile triploid hybrids (3n = 150) of gold fish (Carassius auratus red var., ♀, 2n = 100) and allotetroploid (♂, 2n = 100) display obviously improved disease resistance and much enhanced growth rate than their parents, which have been cultured widely in China. 28126620 1 50 theme red 187:189 arg1 var. 191:194 Carassius auratus red var. 169:194 Carassius auratus red var. 169:194 Sterile triploid hybrids (3n = 150) of gold fish (Carassius auratus red var., ♀, 2n = 100) and allotetroploid (♂, 2n = 100) display obviously improved disease resistance and much enhanced growth rate than their parents, which have been cultured widely in China. 28126620 1 50 theme red 187:189 arg1 2n = 100 200:207 2n = 100 200:207 2n = 100 200:207 Sterile triploid hybrids (3n = 150) of gold fish (Carassius auratus red var., ♀, 2n = 100) and allotetroploid (♂, 2n = 100) display obviously improved disease resistance and much enhanced growth rate than their parents, which have been cultured widely in China. 28126620 9 51 theme innate 1660:1665 arg1 immunity 1667:1674 host antiviral innate immunity 1645:1674 host antiviral innate immunity 1645:1674 All the above data support the conclusion that 3nIFNa2 is an intracellular cytokine functioning importantly in host antiviral innate immunity. 28126620 4 52 theme GCRV 771:774 arg1 infection 776:784 GCRV infection 771:784 GCRV infection 771:784 The transcription of 3nIFNa2 gene was detected in all the examined tissues of triploid hybrid and the mRNA level of 3nIFNa2 was obviously enhanced in response to SVCV and GCRV infection. 28126620 2 53 theme type 407:410 arg1 IFNs 414:417 the type I IFNs 403:417 the type I IFNs of triploid hybrid (3nIFNa2) 403:446 In this paper, one of the type I IFNs of triploid hybrid (3nIFNa2) has been cloned and characterized. 28126620 0 54 theme fish 33:36 arg1 hybrid 18:23 triploid hybrid 9:23 triploid hybrid of gold fish and allotetraploid 9:55 IFNa2 of triploid hybrid of gold fish and allotetraploid is an intracellular antiviral cytokine against SVCV and GCRV. 28126620 4 55 located detected 638:645 arg2 transcription 604:616 The transcription 600:616 The transcription of 3nIFNa2 gene 600:632 The transcription of 3nIFNa2 gene was detected in all the examined tissues of triploid hybrid and the mRNA level of 3nIFNa2 was obviously enhanced in response to SVCV and GCRV infection. 28126620 4 55 located detected 638:645 arg1 tissues 667:673 all the examined tissues 650:673 all the examined tissues of triploid hybrid 650:692 The transcription of 3nIFNa2 gene was detected in all the examined tissues of triploid hybrid and the mRNA level of 3nIFNa2 was obviously enhanced in response to SVCV and GCRV infection. 28126620 9 56 theme intracellular 1595:1607 arg1 3nIFNa2 1581:1587 3nIFNa2 1581:1587 3nIFNa2 1581:1587 All the above data support the conclusion that 3nIFNa2 is an intracellular cytokine functioning importantly in host antiviral innate immunity. 28126620 9 56 theme intracellular 1595:1607 arg1 cytokine 1609:1616 an intracellular cytokine 1592:1616 an intracellular cytokine functioning importantly in host antiviral innate immunity 1592:1674 All the above data support the conclusion that 3nIFNa2 is an intracellular cytokine functioning importantly in host antiviral innate immunity. 28126620 5 57 theme supernatant 915:925 arg1 media 927:931 the supernatant media 911:931 the supernatant media 911:931 3nIFNa2 has been detected in the whole cell lysate of HEK293T cells transfected with plasmids expressing 3nIFNa2 but not in the supernatant media. 28126620 1 58 theme improved 261:268 arg1 resistance 278:287 obviously improved disease resistance 251:287 obviously improved disease resistance 251:287 Sterile triploid hybrids (3n = 150) of gold fish (Carassius auratus red var., ♀, 2n = 100) and allotetroploid (♂, 2n = 100) display obviously improved disease resistance and much enhanced growth rate than their parents, which have been cultured widely in China. 28126620 7 59 link N-linked 1242:1249 arg1 glycosylation 1251:1263 N-linked glycosylation 1242:1263 N-linked glycosylation 1242:1263 Glycosidase digestion analysis demonstrates that 3nIFNa2 is modified with N-linked glycosylation, which occurs on the asparagine (N) of residue 177 of this cytokine. 28126620 1 60 dep allotetroploid 214:227 arg1 ♂ 230:230 ♂ 230:230 ♂ 230:230 Sterile triploid hybrids (3n = 150) of gold fish (Carassius auratus red var., ♀, 2n = 100) and allotetroploid (♂, 2n = 100) display obviously improved disease resistance and much enhanced growth rate than their parents, which have been cultured widely in China. 28126620 3 61 theme gene 515:518 arg1 cDNA 499:502 The full-length cDNA 483:502 The full-length cDNA of 3nIFNa2 gene 483:518 The full-length cDNA of 3nIFNa2 gene consists of 715 nucleotides and the predicted 3nIFNa2 contains 183 amino acids. 28126620 6 62 theme supernatant 1101:1111 arg1 media 1113:1117 the supernatant media 1097:1117 the supernatant media 1097:1117 EPC cells transfected with plasmid expressing 3nIFNa2 at 24 h before SVCV and GCRV infection showed obviously decreased cytopathic effect; and the virus titers in the supernatant media were much lower than those of the control cells. 28126620 4 63 theme 3nIFNa2 621:627 arg1 gene 629:632 3nIFNa2 gene 621:632 3nIFNa2 gene 621:632 The transcription of 3nIFNa2 gene was detected in all the examined tissues of triploid hybrid and the mRNA level of 3nIFNa2 was obviously enhanced in response to SVCV and GCRV infection. 28126620 5 64 theme cells 849:853 arg1 lysate 831:836 the whole cell lysate 816:836 the whole cell lysate of HEK293T cells transfected with plasmids expressing 3nIFNa2 but not in the supernatant media 816:931 3nIFNa2 has been detected in the whole cell lysate of HEK293T cells transfected with plasmids expressing 3nIFNa2 but not in the supernatant media. 28126620 8 65 theme mutant 1354:1359 arg1 3nIFNa2-N177Q 1361:1373 The un-glycosylated mutant 3nIFNa2-N177Q 1334:1373 The un-glycosylated mutant 3nIFNa2-N177Q 1334:1373 The un-glycosylated mutant 3nIFNa2-N177Q shows the similar antiviral ability as that of 3nIFNa2, which suggests that the N-linked glycosylation does not contribute directly to its antiviral property. 28126620 6 66 theme virus 1081:1085 arg1 lower 1129:1133 lower 1129:1133 lower 1129:1133 EPC cells transfected with plasmid expressing 3nIFNa2 at 24 h before SVCV and GCRV infection showed obviously decreased cytopathic effect; and the virus titers in the supernatant media were much lower than those of the control cells. 28126620 6 66 theme virus 1081:1085 arg1 titers 1087:1092 the virus titers 1077:1092 the virus titers in the supernatant media 1077:1117 EPC cells transfected with plasmid expressing 3nIFNa2 at 24 h before SVCV and GCRV infection showed obviously decreased cytopathic effect; and the virus titers in the supernatant media were much lower than those of the control cells. 28126620 1 67 theme Sterile 119:125 arg1 hybrids 136:142 Sterile triploid hybrids 119:142 Sterile triploid hybrids (3n = 150) of gold fish (Carassius auratus red var., ♀, 2n = 100) and allotetroploid (♂, 2n = 100) 119:241 Sterile triploid hybrids (3n = 150) of gold fish (Carassius auratus red var., ♀, 2n = 100) and allotetroploid (♂, 2n = 100) display obviously improved disease resistance and much enhanced growth rate than their parents, which have been cultured widely in China. 28126620 1 67 theme Sterile 119:125 arg1 3n = 150 145:152 3n = 150 145:152 3n = 150 145:152 Sterile triploid hybrids (3n = 150) of gold fish (Carassius auratus red var., ♀, 2n = 100) and allotetroploid (♂, 2n = 100) display obviously improved disease resistance and much enhanced growth rate than their parents, which have been cultured widely in China. 28126620 4 68 theme triploid 678:685 arg1 hybrid 687:692 triploid hybrid 678:692 triploid hybrid 678:692 The transcription of 3nIFNa2 gene was detected in all the examined tissues of triploid hybrid and the mRNA level of 3nIFNa2 was obviously enhanced in response to SVCV and GCRV infection. 28126620 2 69 theme I 412:412 arg1 IFNs 414:417 the type I IFNs 403:417 the type I IFNs of triploid hybrid (3nIFNa2) 403:446 In this paper, one of the type I IFNs of triploid hybrid (3nIFNa2) has been cloned and characterized. 28126620 3 70 theme predicted 556:564 arg1 3nIFNa2 566:572 the predicted 3nIFNa2 552:572 the predicted 3nIFNa2 552:572 The full-length cDNA of 3nIFNa2 gene consists of 715 nucleotides and the predicted 3nIFNa2 contains 183 amino acids. 28126620 4 71 theme hybrid 687:692 arg1 tissues 667:673 all the examined tissues 650:673 all the examined tissues of triploid hybrid 650:692 The transcription of 3nIFNa2 gene was detected in all the examined tissues of triploid hybrid and the mRNA level of 3nIFNa2 was obviously enhanced in response to SVCV and GCRV infection. 28126620 7 72 theme Glycosidase 1168:1178 arg1 analysis 1190:1197 Glycosidase digestion analysis 1168:1197 Glycosidase digestion analysis 1168:1197 Glycosidase digestion analysis demonstrates that 3nIFNa2 is modified with N-linked glycosylation, which occurs on the asparagine (N) of residue 177 of this cytokine. 28126620 1 73 theme triploid 127:134 arg1 hybrids 136:142 Sterile triploid hybrids 119:142 Sterile triploid hybrids (3n = 150) of gold fish (Carassius auratus red var., ♀, 2n = 100) and allotetroploid (♂, 2n = 100) 119:241 Sterile triploid hybrids (3n = 150) of gold fish (Carassius auratus red var., ♀, 2n = 100) and allotetroploid (♂, 2n = 100) display obviously improved disease resistance and much enhanced growth rate than their parents, which have been cultured widely in China. 28126620 1 73 theme triploid 127:134 arg1 3n = 150 145:152 3n = 150 145:152 3n = 150 145:152 Sterile triploid hybrids (3n = 150) of gold fish (Carassius auratus red var., ♀, 2n = 100) and allotetroploid (♂, 2n = 100) display obviously improved disease resistance and much enhanced growth rate than their parents, which have been cultured widely in China. 28126620 0 74 theme allotetraploid 42:55 arg1 hybrid 18:23 triploid hybrid 9:23 triploid hybrid of gold fish and allotetraploid 9:55 IFNa2 of triploid hybrid of gold fish and allotetraploid is an intracellular antiviral cytokine against SVCV and GCRV. 28126620 1 75 theme disease 270:276 arg1 resistance 278:287 obviously improved disease resistance 251:287 obviously improved disease resistance 251:287 Sterile triploid hybrids (3n = 150) of gold fish (Carassius auratus red var., ♀, 2n = 100) and allotetroploid (♂, 2n = 100) display obviously improved disease resistance and much enhanced growth rate than their parents, which have been cultured widely in China. 28126620 1 76 dep Carassius 169:177 arg1 auratus 179:185 auratus 179:185 auratus 179:185 Sterile triploid hybrids (3n = 150) of gold fish (Carassius auratus red var., ♀, 2n = 100) and allotetroploid (♂, 2n = 100) display obviously improved disease resistance and much enhanced growth rate than their parents, which have been cultured widely in China. 28126620 2 77 theme triploid 422:429 arg1 3nIFNa2 439:445 3nIFNa2 439:445 3nIFNa2 439:445 In this paper, one of the type I IFNs of triploid hybrid (3nIFNa2) has been cloned and characterized. 28126620 2 77 theme triploid 422:429 arg1 hybrid 431:436 triploid hybrid 422:436 triploid hybrid (3nIFNa2) 422:446 In this paper, one of the type I IFNs of triploid hybrid (3nIFNa2) has been cloned and characterized. 26334531 0 0 theme Extracellular 80:92 arg1 Glycosaminoglycans 101:118 Extracellular Matrix Glycosaminoglycans 80:118 Extracellular Matrix Glycosaminoglycans 80:118 Intracellular Survival of Leishmania major Depends on Uptake and Degradation of Extracellular Matrix Glycosaminoglycans by Macrophages. 26334531 5 1 contain have 895:898 arg2 access 900:905 access 900:905 access to GlcNAc 900:915 In contrast, the L. major ∆gnat mutant induced normal skin lesions in mice, suggesting that these parasites have access to GlcNAc in tissue macrophages. 26334531 5 1 contain have 895:898 arg1 parasites 885:893 these parasites 879:893 these parasites 879:893 In contrast, the L. major ∆gnat mutant induced normal skin lesions in mice, suggesting that these parasites have access to GlcNAc in tissue macrophages. 26334531 1 2 theme phagolysosome 178:190 arg1 compartment 192:202 the phagolysosome compartment 174:202 the phagolysosome compartment of mammalian macrophages 174:227 Leishmania parasites replicate within the phagolysosome compartment of mammalian macrophages. 26334531 6 3 from growth 954:959 arg1 macrophages 995:1005 ex vivo infected macrophages 978:1005 ex vivo infected macrophages 978:1005 Intracellular growth of the mutant in ex vivo infected macrophages was restored by supplementation of the macrophage medium with hyaluronan, a GlcNAc-rich extracellular matrix glycosaminoglycan. 26334531 5 4 theme tissue 920:925 arg1 macrophages 927:937 tissue macrophages 920:937 tissue macrophages 920:937 In contrast, the L. major ∆gnat mutant induced normal skin lesions in mice, suggesting that these parasites have access to GlcNAc in tissue macrophages. 26334531 6 5 theme matrix 1109:1114 arg1 hyaluronan 1069:1078 hyaluronan 1069:1078 hyaluronan 1069:1078 Intracellular growth of the mutant in ex vivo infected macrophages was restored by supplementation of the macrophage medium with hyaluronan, a GlcNAc-rich extracellular matrix glycosaminoglycan. 26334531 6 5 theme matrix 1109:1114 arg1 glycosaminoglycan 1116:1132 a GlcNAc-rich extracellular matrix glycosaminoglycan 1081:1132 a GlcNAc-rich extracellular matrix glycosaminoglycan 1081:1132 Intracellular growth of the mutant in ex vivo infected macrophages was restored by supplementation of the macrophage medium with hyaluronan, a GlcNAc-rich extracellular matrix glycosaminoglycan. 26334531 8 6 theme favorable 1488:1496 arg1 niche 1498:1502 a uniquely favorable niche 1477:1502 a uniquely favorable niche for these parasites 1477:1522 These findings suggest that the constitutive internalization and degradation of host glycosaminoglycans by macrophages provides Leishmania with essential carbon sources, creating a uniquely favorable niche for these parasites. 26334531 0 7 theme Glycosaminoglycans 101:118 arg1 Degradation 65:75 Degradation 65:75 Degradation 65:75 Intracellular Survival of Leishmania major Depends on Uptake and Degradation of Extracellular Matrix Glycosaminoglycans by Macrophages. 26334531 0 7 theme Glycosaminoglycans 101:118 arg1 Uptake 54:59 Uptake 54:59 Uptake 54:59 Intracellular Survival of Leishmania major Depends on Uptake and Degradation of Extracellular Matrix Glycosaminoglycans by Macrophages. 26334531 4 8 theme exogenous 769:777 arg1 GlcNAc 779:784 exogenous GlcNAc 769:784 exogenous GlcNAc 769:784 This mutant was unable to grow or survive in ex vivo infected macrophages even when macrophages were cultivated in presence of exogenous GlcNAc. 26334531 0 9 theme Matrix 94:99 arg1 Glycosaminoglycans 101:118 Extracellular Matrix Glycosaminoglycans 80:118 Extracellular Matrix Glycosaminoglycans 80:118 Intracellular Survival of Leishmania major Depends on Uptake and Degradation of Extracellular Matrix Glycosaminoglycans by Macrophages. 26334531 7 10 from lesions 1215:1221 arg1 turned-over 1176:1186 turned-over 1176:1186 turned-over 1176:1186 Hyaluronan is present and constitutively turned-over in Leishmania-induced skin lesions and is efficiently internalized into Leishmania containing phagolysosomes. 26334531 8 11 theme carbon 1452:1457 arg1 sources 1459:1465 essential carbon sources 1442:1465 essential carbon sources 1442:1465 These findings suggest that the constitutive internalization and degradation of host glycosaminoglycans by macrophages provides Leishmania with essential carbon sources, creating a uniquely favorable niche for these parasites. 26334531 2 12 theme nutrient 315:322 arg1 composition 324:334 the nutrient composition 311:334 the nutrient composition of the phagolysosome 311:355 Although Leishmania depend on sugars as a major carbon source during infections, the nutrient composition of the phagolysosome remains poorly described. 26334531 6 13 theme infected 986:993 arg1 macrophages 995:1005 ex vivo infected macrophages 978:1005 ex vivo infected macrophages 978:1005 Intracellular growth of the mutant in ex vivo infected macrophages was restored by supplementation of the macrophage medium with hyaluronan, a GlcNAc-rich extracellular matrix glycosaminoglycan. 26334531 8 14 theme host 1378:1381 arg1 glycosaminoglycans 1383:1400 host glycosaminoglycans 1378:1400 host glycosaminoglycans 1378:1400 These findings suggest that the constitutive internalization and degradation of host glycosaminoglycans by macrophages provides Leishmania with essential carbon sources, creating a uniquely favorable niche for these parasites. 26334531 8 15 theme constitutive 1330:1341 arg1 internalization 1343:1357 constitutive internalization 1330:1357 constitutive internalization 1330:1357 These findings suggest that the constitutive internalization and degradation of host glycosaminoglycans by macrophages provides Leishmania with essential carbon sources, creating a uniquely favorable niche for these parasites. 26334531 6 16 theme extracellular 1095:1107 arg1 hyaluronan 1069:1078 hyaluronan 1069:1078 hyaluronan 1069:1078 Intracellular growth of the mutant in ex vivo infected macrophages was restored by supplementation of the macrophage medium with hyaluronan, a GlcNAc-rich extracellular matrix glycosaminoglycan. 26334531 6 16 theme extracellular 1095:1107 arg1 glycosaminoglycan 1116:1132 a GlcNAc-rich extracellular matrix glycosaminoglycan 1081:1132 a GlcNAc-rich extracellular matrix glycosaminoglycan 1081:1132 Intracellular growth of the mutant in ex vivo infected macrophages was restored by supplementation of the macrophage medium with hyaluronan, a GlcNAc-rich extracellular matrix glycosaminoglycan. 26334531 5 17 theme ∆gnat 813:817 arg1 mutant 819:824 the L. major ∆gnat mutant 800:824 the L. major ∆gnat mutant 800:824 In contrast, the L. major ∆gnat mutant induced normal skin lesions in mice, suggesting that these parasites have access to GlcNAc in tissue macrophages. 26334531 7 18 dep present 1149:1155 arg1 turned-over 1176:1186 turned-over 1176:1186 turned-over 1176:1186 Hyaluronan is present and constitutively turned-over in Leishmania-induced skin lesions and is efficiently internalized into Leishmania containing phagolysosomes. 26334531 0 19 theme Intracellular 0:12 arg1 Survival 14:21 Intracellular Survival 0:21 Intracellular Survival of Leishmania major 0:41 Intracellular Survival of Leishmania major Depends on Uptake and Degradation of Extracellular Matrix Glycosaminoglycans by Macrophages. 26334531 1 20 theme mammalian 207:215 arg1 macrophages 217:227 mammalian macrophages 207:227 mammalian macrophages 207:227 Leishmania parasites replicate within the phagolysosome compartment of mammalian macrophages. 26334531 3 21 theme carbon 420:425 arg1 source 427:432 the sugar carbon source 410:432 the sugar carbon source 410:432 To determine the origin of the sugar carbon source in macrophage phagolysosomes, we have generated a N-acetylglucosamine acetyltransferase (GNAT) deficient Leishmania major mutant (∆gnat) that is auxotrophic for the amino sugar, N-acetylglucosamine (GlcNAc). 26334531 6 22 theme mutant 968:973 arg1 growth 954:959 Intracellular growth 940:959 Intracellular growth of the mutant in ex vivo infected macrophages 940:1005 Intracellular growth of the mutant in ex vivo infected macrophages was restored by supplementation of the macrophage medium with hyaluronan, a GlcNAc-rich extracellular matrix glycosaminoglycan. 26334531 1 23 theme macrophages 217:227 arg1 compartment 192:202 the phagolysosome compartment 174:202 the phagolysosome compartment of mammalian macrophages 174:227 Leishmania parasites replicate within the phagolysosome compartment of mammalian macrophages. 26334531 3 24 theme source 427:432 arg1 origin 400:405 the origin 396:405 the origin of the sugar carbon source in macrophage phagolysosomes 396:461 To determine the origin of the sugar carbon source in macrophage phagolysosomes, we have generated a N-acetylglucosamine acetyltransferase (GNAT) deficient Leishmania major mutant (∆gnat) that is auxotrophic for the amino sugar, N-acetylglucosamine (GlcNAc). 26334531 7 25 theme skin 1210:1213 arg1 lesions 1215:1221 Leishmania-induced skin lesions 1191:1221 Leishmania-induced skin lesions 1191:1221 Hyaluronan is present and constitutively turned-over in Leishmania-induced skin lesions and is efficiently internalized into Leishmania containing phagolysosomes. 26334531 2 26 theme phagolysosome 343:355 arg1 composition 324:334 the nutrient composition 311:334 the nutrient composition of the phagolysosome 311:355 Although Leishmania depend on sugars as a major carbon source during infections, the nutrient composition of the phagolysosome remains poorly described. 26334531 4 27 theme ex 687:688 arg1 macrophages 704:714 ex vivo infected macrophages 687:714 ex vivo infected macrophages 687:714 This mutant was unable to grow or survive in ex vivo infected macrophages even when macrophages were cultivated in presence of exogenous GlcNAc. 26334531 5 28 theme normal 834:839 arg1 lesions 846:852 normal skin lesions 834:852 normal skin lesions in mice 834:860 In contrast, the L. major ∆gnat mutant induced normal skin lesions in mice, suggesting that these parasites have access to GlcNAc in tissue macrophages. 26334531 6 29 theme ex 978:979 arg1 macrophages 995:1005 ex vivo infected macrophages 978:1005 ex vivo infected macrophages 978:1005 Intracellular growth of the mutant in ex vivo infected macrophages was restored by supplementation of the macrophage medium with hyaluronan, a GlcNAc-rich extracellular matrix glycosaminoglycan. 26334531 4 30 theme GlcNAc 779:784 arg1 presence 757:764 presence 757:764 presence of exogenous GlcNAc 757:784 This mutant was unable to grow or survive in ex vivo infected macrophages even when macrophages were cultivated in presence of exogenous GlcNAc. 26334531 6 31 with supplementation 1023:1037 arg1 hyaluronan 1069:1078 hyaluronan 1069:1078 hyaluronan 1069:1078 Intracellular growth of the mutant in ex vivo infected macrophages was restored by supplementation of the macrophage medium with hyaluronan, a GlcNAc-rich extracellular matrix glycosaminoglycan. 26334531 6 31 with supplementation 1023:1037 arg1 glycosaminoglycan 1116:1132 a GlcNAc-rich extracellular matrix glycosaminoglycan 1081:1132 a GlcNAc-rich extracellular matrix glycosaminoglycan 1081:1132 Intracellular growth of the mutant in ex vivo infected macrophages was restored by supplementation of the macrophage medium with hyaluronan, a GlcNAc-rich extracellular matrix glycosaminoglycan. 26334531 3 32 theme sugar 414:418 arg1 source 427:432 the sugar carbon source 410:432 the sugar carbon source 410:432 To determine the origin of the sugar carbon source in macrophage phagolysosomes, we have generated a N-acetylglucosamine acetyltransferase (GNAT) deficient Leishmania major mutant (∆gnat) that is auxotrophic for the amino sugar, N-acetylglucosamine (GlcNAc). 26334531 7 33 contain containing 1271:1280 arg1 Leishmania 1260:1269 Leishmania 1260:1269 Leishmania containing phagolysosomes 1260:1295 Hyaluronan is present and constitutively turned-over in Leishmania-induced skin lesions and is efficiently internalized into Leishmania containing phagolysosomes. 26334531 7 33 contain containing 1271:1280 arg2 phagolysosomes 1282:1295 phagolysosomes 1282:1295 phagolysosomes 1282:1295 Hyaluronan is present and constitutively turned-over in Leishmania-induced skin lesions and is efficiently internalized into Leishmania containing phagolysosomes. 26334531 3 34 theme amino 599:603 arg1 N-acetylglucosamine 612:630 N-acetylglucosamine 612:630 N-acetylglucosamine (GlcNAc) 612:639 To determine the origin of the sugar carbon source in macrophage phagolysosomes, we have generated a N-acetylglucosamine acetyltransferase (GNAT) deficient Leishmania major mutant (∆gnat) that is auxotrophic for the amino sugar, N-acetylglucosamine (GlcNAc). 26334531 3 34 theme amino 599:603 arg1 sugar 605:609 the amino sugar 595:609 the amino sugar 595:609 To determine the origin of the sugar carbon source in macrophage phagolysosomes, we have generated a N-acetylglucosamine acetyltransferase (GNAT) deficient Leishmania major mutant (∆gnat) that is auxotrophic for the amino sugar, N-acetylglucosamine (GlcNAc). 26334531 7 35 theme Leishmania-induced 1191:1208 arg1 lesions 1215:1221 Leishmania-induced skin lesions 1191:1221 Leishmania-induced skin lesions 1191:1221 Hyaluronan is present and constitutively turned-over in Leishmania-induced skin lesions and is efficiently internalized into Leishmania containing phagolysosomes. 26334531 3 36 theme major 550:554 arg1 auxotrophic 579:589 auxotrophic 579:589 auxotrophic 579:589 To determine the origin of the sugar carbon source in macrophage phagolysosomes, we have generated a N-acetylglucosamine acetyltransferase (GNAT) deficient Leishmania major mutant (∆gnat) that is auxotrophic for the amino sugar, N-acetylglucosamine (GlcNAc). 26334531 3 36 theme major 550:554 arg1 ∆gnat 564:568 ∆gnat 564:568 ∆gnat 564:568 To determine the origin of the sugar carbon source in macrophage phagolysosomes, we have generated a N-acetylglucosamine acetyltransferase (GNAT) deficient Leishmania major mutant (∆gnat) that is auxotrophic for the amino sugar, N-acetylglucosamine (GlcNAc). 26334531 3 36 theme major 550:554 arg1 mutant 556:561 a N-acetylglucosamine acetyltransferase (GNAT) deficient Leishmania major mutant 482:561 a N-acetylglucosamine acetyltransferase (GNAT) deficient Leishmania major mutant (∆gnat) that is auxotrophic for the amino sugar, N-acetylglucosamine (GlcNAc) 482:639 To determine the origin of the sugar carbon source in macrophage phagolysosomes, we have generated a N-acetylglucosamine acetyltransferase (GNAT) deficient Leishmania major mutant (∆gnat) that is auxotrophic for the amino sugar, N-acetylglucosamine (GlcNAc). 26334531 2 37 theme major 272:276 arg1 source 285:290 a major carbon source 270:290 a major carbon source during infections 270:308 Although Leishmania depend on sugars as a major carbon source during infections, the nutrient composition of the phagolysosome remains poorly described. 26334531 6 38 theme medium 1057:1062 arg1 supplementation 1023:1037 supplementation 1023:1037 supplementation of the macrophage medium with hyaluronan, a GlcNAc-rich extracellular matrix glycosaminoglycan 1023:1132 Intracellular growth of the mutant in ex vivo infected macrophages was restored by supplementation of the macrophage medium with hyaluronan, a GlcNAc-rich extracellular matrix glycosaminoglycan. 26334531 0 39 theme major 37:41 arg1 Survival 14:21 Intracellular Survival 0:21 Intracellular Survival of Leishmania major 0:41 Intracellular Survival of Leishmania major Depends on Uptake and Degradation of Extracellular Matrix Glycosaminoglycans by Macrophages. 26334531 5 40 theme L. 804:805 arg1 mutant 819:824 the L. major ∆gnat mutant 800:824 the L. major ∆gnat mutant 800:824 In contrast, the L. major ∆gnat mutant induced normal skin lesions in mice, suggesting that these parasites have access to GlcNAc in tissue macrophages. 26334531 3 41 from origin 400:405 arg1 phagolysosomes 448:461 macrophage phagolysosomes 437:461 macrophage phagolysosomes 437:461 To determine the origin of the sugar carbon source in macrophage phagolysosomes, we have generated a N-acetylglucosamine acetyltransferase (GNAT) deficient Leishmania major mutant (∆gnat) that is auxotrophic for the amino sugar, N-acetylglucosamine (GlcNAc). 26334531 6 42 theme macrophage 1046:1055 arg1 medium 1057:1062 the macrophage medium 1042:1062 the macrophage medium 1042:1062 Intracellular growth of the mutant in ex vivo infected macrophages was restored by supplementation of the macrophage medium with hyaluronan, a GlcNAc-rich extracellular matrix glycosaminoglycan. 26334531 5 43 theme major 807:811 arg1 mutant 819:824 the L. major ∆gnat mutant 800:824 the L. major ∆gnat mutant 800:824 In contrast, the L. major ∆gnat mutant induced normal skin lesions in mice, suggesting that these parasites have access to GlcNAc in tissue macrophages. 26334531 5 44 theme skin 841:844 arg1 lesions 846:852 normal skin lesions 834:852 normal skin lesions in mice 834:860 In contrast, the L. major ∆gnat mutant induced normal skin lesions in mice, suggesting that these parasites have access to GlcNAc in tissue macrophages. 26334531 8 45 theme glycosaminoglycans 1383:1400 arg1 degradation 1363:1373 degradation 1363:1373 degradation 1363:1373 These findings suggest that the constitutive internalization and degradation of host glycosaminoglycans by macrophages provides Leishmania with essential carbon sources, creating a uniquely favorable niche for these parasites. 26334531 8 45 theme glycosaminoglycans 1383:1400 arg1 internalization 1343:1357 constitutive internalization 1330:1357 constitutive internalization 1330:1357 These findings suggest that the constitutive internalization and degradation of host glycosaminoglycans by macrophages provides Leishmania with essential carbon sources, creating a uniquely favorable niche for these parasites. 26334531 3 46 theme macrophage 437:446 arg1 phagolysosomes 448:461 macrophage phagolysosomes 437:461 macrophage phagolysosomes 437:461 To determine the origin of the sugar carbon source in macrophage phagolysosomes, we have generated a N-acetylglucosamine acetyltransferase (GNAT) deficient Leishmania major mutant (∆gnat) that is auxotrophic for the amino sugar, N-acetylglucosamine (GlcNAc). 26334531 0 47 dep major 37:41 arg1 Leishmania 26:35 Leishmania major 26:41 Leishmania major 26:41 Intracellular Survival of Leishmania major Depends on Uptake and Degradation of Extracellular Matrix Glycosaminoglycans by Macrophages. 26334531 5 48 from lesions 846:852 arg1 mice 857:860 mice 857:860 mice 857:860 In contrast, the L. major ∆gnat mutant induced normal skin lesions in mice, suggesting that these parasites have access to GlcNAc in tissue macrophages. 26334531 1 49 theme Leishmania 136:145 arg1 parasites 147:155 Leishmania parasites 136:155 Leishmania parasites 136:155 Leishmania parasites replicate within the phagolysosome compartment of mammalian macrophages. 26334531 6 50 theme Intracellular 940:952 arg1 growth 954:959 Intracellular growth 940:959 Intracellular growth of the mutant in ex vivo infected macrophages 940:1005 Intracellular growth of the mutant in ex vivo infected macrophages was restored by supplementation of the macrophage medium with hyaluronan, a GlcNAc-rich extracellular matrix glycosaminoglycan. 26334531 3 51 dep major 550:554 arg1 Leishmania 539:548 Leishmania 539:548 Leishmania 539:548 To determine the origin of the sugar carbon source in macrophage phagolysosomes, we have generated a N-acetylglucosamine acetyltransferase (GNAT) deficient Leishmania major mutant (∆gnat) that is auxotrophic for the amino sugar, N-acetylglucosamine (GlcNAc). 26334531 4 52 dep ex 687:688 arg1 vivo 690:693 vivo 690:693 vivo 690:693 This mutant was unable to grow or survive in ex vivo infected macrophages even when macrophages were cultivated in presence of exogenous GlcNAc. 26334531 3 53 theme deficient 529:537 arg1 auxotrophic 579:589 auxotrophic 579:589 auxotrophic 579:589 To determine the origin of the sugar carbon source in macrophage phagolysosomes, we have generated a N-acetylglucosamine acetyltransferase (GNAT) deficient Leishmania major mutant (∆gnat) that is auxotrophic for the amino sugar, N-acetylglucosamine (GlcNAc). 26334531 3 53 theme deficient 529:537 arg1 ∆gnat 564:568 ∆gnat 564:568 ∆gnat 564:568 To determine the origin of the sugar carbon source in macrophage phagolysosomes, we have generated a N-acetylglucosamine acetyltransferase (GNAT) deficient Leishmania major mutant (∆gnat) that is auxotrophic for the amino sugar, N-acetylglucosamine (GlcNAc). 26334531 3 53 theme deficient 529:537 arg1 mutant 556:561 a N-acetylglucosamine acetyltransferase (GNAT) deficient Leishmania major mutant 482:561 a N-acetylglucosamine acetyltransferase (GNAT) deficient Leishmania major mutant (∆gnat) that is auxotrophic for the amino sugar, N-acetylglucosamine (GlcNAc) 482:639 To determine the origin of the sugar carbon source in macrophage phagolysosomes, we have generated a N-acetylglucosamine acetyltransferase (GNAT) deficient Leishmania major mutant (∆gnat) that is auxotrophic for the amino sugar, N-acetylglucosamine (GlcNAc). 26334531 8 54 theme essential 1442:1450 arg1 sources 1459:1465 essential carbon sources 1442:1465 essential carbon sources 1442:1465 These findings suggest that the constitutive internalization and degradation of host glycosaminoglycans by macrophages provides Leishmania with essential carbon sources, creating a uniquely favorable niche for these parasites. 26334531 6 55 dep ex 978:979 arg1 vivo 981:984 vivo 981:984 vivo 981:984 Intracellular growth of the mutant in ex vivo infected macrophages was restored by supplementation of the macrophage medium with hyaluronan, a GlcNAc-rich extracellular matrix glycosaminoglycan. 26334531 8 56 dep internalization 1343:1357 arg1 the 1326:1328 the 1326:1328 the 1326:1328 These findings suggest that the constitutive internalization and degradation of host glycosaminoglycans by macrophages provides Leishmania with essential carbon sources, creating a uniquely favorable niche for these parasites. 26334531 6 57 theme GlcNAc-rich 1083:1093 arg1 hyaluronan 1069:1078 hyaluronan 1069:1078 hyaluronan 1069:1078 Intracellular growth of the mutant in ex vivo infected macrophages was restored by supplementation of the macrophage medium with hyaluronan, a GlcNAc-rich extracellular matrix glycosaminoglycan. 26334531 6 57 theme GlcNAc-rich 1083:1093 arg1 glycosaminoglycan 1116:1132 a GlcNAc-rich extracellular matrix glycosaminoglycan 1081:1132 a GlcNAc-rich extracellular matrix glycosaminoglycan 1081:1132 Intracellular growth of the mutant in ex vivo infected macrophages was restored by supplementation of the macrophage medium with hyaluronan, a GlcNAc-rich extracellular matrix glycosaminoglycan. 26334531 7 58 from turned-over 1176:1186 arg1 lesions 1215:1221 Leishmania-induced skin lesions 1191:1221 Leishmania-induced skin lesions 1191:1221 Hyaluronan is present and constitutively turned-over in Leishmania-induced skin lesions and is efficiently internalized into Leishmania containing phagolysosomes. 26334531 2 59 theme carbon 278:283 arg1 source 285:290 a major carbon source 270:290 a major carbon source during infections 270:308 Although Leishmania depend on sugars as a major carbon source during infections, the nutrient composition of the phagolysosome remains poorly described. 26334531 4 60 theme infected 695:702 arg1 macrophages 704:714 ex vivo infected macrophages 687:714 ex vivo infected macrophages 687:714 This mutant was unable to grow or survive in ex vivo infected macrophages even when macrophages were cultivated in presence of exogenous GlcNAc. 27186633 0 0 link N-linked 114:121 arg1 glycopeptides 123:135 N-linked glycopeptides 114:135 N-linked glycopeptides 114:135 Post-synthetic modification of an amino-functionalized metal-organic framework for highly efficient enrichment of N-linked glycopeptides. 27186633 3 1 theme generic 492:498 arg1 route 518:522 the generic functionalization route 488:522 the generic functionalization route from amino-derived MOFs 488:546 More importantly, the generic functionalization route from amino-derived MOFs opens a new perspective in material design in sample preparation. 27186633 3 2 from MOFs 543:546 arg1 route 518:522 the generic functionalization route 488:522 the generic functionalization route from amino-derived MOFs 488:546 More importantly, the generic functionalization route from amino-derived MOFs opens a new perspective in material design in sample preparation. 27186633 1 3 theme post-synthetic 251:264 arg1 modification 266:277 a simple two step post-synthetic modification 233:277 a simple two step post-synthetic modification of MIL-101(Cr)-NH2 233:296 A maltose-functionalized metal-organic framework (MOF), MIL-101(Cr)-maltose, was developed via a simple two step post-synthetic modification of MIL-101(Cr)-NH2. 27186633 3 4 theme functionalization 500:516 arg1 route 518:522 the generic functionalization route 488:522 the generic functionalization route from amino-derived MOFs 488:546 More importantly, the generic functionalization route from amino-derived MOFs opens a new perspective in material design in sample preparation. 27186633 0 5 theme glycopeptides 123:135 arg1 enrichment 100:109 highly efficient enrichment 83:109 highly efficient enrichment of N-linked glycopeptides 83:135 Post-synthetic modification of an amino-functionalized metal-organic framework for highly efficient enrichment of N-linked glycopeptides. 27186633 0 6 theme N-linked 114:121 arg1 glycopeptides 123:135 N-linked glycopeptides 114:135 N-linked glycopeptides 114:135 Post-synthetic modification of an amino-functionalized metal-organic framework for highly efficient enrichment of N-linked glycopeptides. 27186633 1 7 theme MIL-101 282:288 arg1 -NH2 293:296 MIL-101(Cr)-NH2 282:296 MIL-101(Cr)-NH2 282:296 A maltose-functionalized metal-organic framework (MOF), MIL-101(Cr)-maltose, was developed via a simple two step post-synthetic modification of MIL-101(Cr)-NH2. 27186633 3 8 theme amino-derived 529:541 arg1 MOFs 543:546 amino-derived MOFs 529:546 amino-derived MOFs 529:546 More importantly, the generic functionalization route from amino-derived MOFs opens a new perspective in material design in sample preparation. 27186633 2 9 theme high 426:429 arg1 efficiency 431:440 its high efficiency 422:440 its high efficiency 422:440 With the use of this nanomaterial, 33 glycopeptides were detected from the digest of human immunoglobulin G, demonstrating its high efficiency in glycoproteomic analysis. 27186633 0 10 theme Post-synthetic 0:13 arg1 modification 15:26 Post-synthetic modification 0:26 Post-synthetic modification of an amino-functionalized metal-organic framework for highly efficient enrichment of N-linked glycopeptides 0:135 Post-synthetic modification of an amino-functionalized metal-organic framework for highly efficient enrichment of N-linked glycopeptides. 27186633 0 11 gly glycopeptides 123:135 arg2 glycopeptides 123:135 N-linked glycopeptides 114:135 N-linked glycopeptides 114:135 Post-synthetic modification of an amino-functionalized metal-organic framework for highly efficient enrichment of N-linked glycopeptides. 27186633 3 12 from design 584:589 arg1 preparation 601:611 sample preparation 594:611 sample preparation 594:611 More importantly, the generic functionalization route from amino-derived MOFs opens a new perspective in material design in sample preparation. 27186633 1 13 theme -maltose 205:212 arg1 framework 177:185 A maltose-functionalized metal-organic framework 138:185 A maltose-functionalized metal-organic framework (MOF) 138:191 A maltose-functionalized metal-organic framework (MOF), MIL-101(Cr)-maltose, was developed via a simple two step post-synthetic modification of MIL-101(Cr)-NH2. 27186633 1 13 theme -maltose 205:212 arg1 MOF 188:190 MOF 188:190 MOF 188:190 A maltose-functionalized metal-organic framework (MOF), MIL-101(Cr)-maltose, was developed via a simple two step post-synthetic modification of MIL-101(Cr)-NH2. 27186633 3 14 theme new 556:558 arg1 perspective 560:570 a new perspective 554:570 a new perspective in material design in sample preparation 554:611 More importantly, the generic functionalization route from amino-derived MOFs opens a new perspective in material design in sample preparation. 27186633 3 15 theme material 575:582 arg1 design 584:589 material design 575:589 material design in sample preparation 575:611 More importantly, the generic functionalization route from amino-derived MOFs opens a new perspective in material design in sample preparation. 27186633 2 16 theme G 405:405 arg1 digest 374:379 the digest 370:379 the digest of human immunoglobulin G 370:405 With the use of this nanomaterial, 33 glycopeptides were detected from the digest of human immunoglobulin G, demonstrating its high efficiency in glycoproteomic analysis. 27186633 0 17 theme metal-organic 55:67 arg1 framework 69:77 an amino-functionalized metal-organic framework 31:77 an amino-functionalized metal-organic framework for highly efficient enrichment of N-linked glycopeptides 31:135 Post-synthetic modification of an amino-functionalized metal-organic framework for highly efficient enrichment of N-linked glycopeptides. 27186633 1 18 theme -NH2 293:296 arg1 modification 266:277 a simple two step post-synthetic modification 233:277 a simple two step post-synthetic modification of MIL-101(Cr)-NH2 233:296 A maltose-functionalized metal-organic framework (MOF), MIL-101(Cr)-maltose, was developed via a simple two step post-synthetic modification of MIL-101(Cr)-NH2. 27186633 3 19 theme sample 594:599 arg1 preparation 601:611 sample preparation 594:611 sample preparation 594:611 More importantly, the generic functionalization route from amino-derived MOFs opens a new perspective in material design in sample preparation. 27186633 2 20 theme immunoglobulin 390:403 arg1 G 405:405 human immunoglobulin G 384:405 human immunoglobulin G 384:405 With the use of this nanomaterial, 33 glycopeptides were detected from the digest of human immunoglobulin G, demonstrating its high efficiency in glycoproteomic analysis. 27186633 0 21 theme amino-functionalized 34:53 arg1 framework 69:77 an amino-functionalized metal-organic framework 31:77 an amino-functionalized metal-organic framework for highly efficient enrichment of N-linked glycopeptides 31:135 Post-synthetic modification of an amino-functionalized metal-organic framework for highly efficient enrichment of N-linked glycopeptides. 27186633 2 22 gly glycopeptides 337:349 arg2 glycopeptides 337:349 33 glycopeptides 334:349 33 glycopeptides 334:349 With the use of this nanomaterial, 33 glycopeptides were detected from the digest of human immunoglobulin G, demonstrating its high efficiency in glycoproteomic analysis. 27186633 2 23 theme human 384:388 arg1 G 405:405 human immunoglobulin G 384:405 human immunoglobulin G 384:405 With the use of this nanomaterial, 33 glycopeptides were detected from the digest of human immunoglobulin G, demonstrating its high efficiency in glycoproteomic analysis. 27186633 2 24 theme glycoproteomic 445:458 arg1 analysis 460:467 glycoproteomic analysis 445:467 glycoproteomic analysis 445:467 With the use of this nanomaterial, 33 glycopeptides were detected from the digest of human immunoglobulin G, demonstrating its high efficiency in glycoproteomic analysis. 27186633 3 25 link amino-derived 529:541 arg1 MOFs 543:546 amino-derived MOFs 529:546 amino-derived MOFs 529:546 More importantly, the generic functionalization route from amino-derived MOFs opens a new perspective in material design in sample preparation. 27186633 1 26 theme maltose-functionalized 140:161 arg1 framework 177:185 A maltose-functionalized metal-organic framework 138:185 A maltose-functionalized metal-organic framework (MOF) 138:191 A maltose-functionalized metal-organic framework (MOF), MIL-101(Cr)-maltose, was developed via a simple two step post-synthetic modification of MIL-101(Cr)-NH2. 27186633 1 26 theme maltose-functionalized 140:161 arg1 MOF 188:190 MOF 188:190 MOF 188:190 A maltose-functionalized metal-organic framework (MOF), MIL-101(Cr)-maltose, was developed via a simple two step post-synthetic modification of MIL-101(Cr)-NH2. 27186633 0 27 theme framework 69:77 arg1 modification 15:26 Post-synthetic modification 0:26 Post-synthetic modification of an amino-functionalized metal-organic framework for highly efficient enrichment of N-linked glycopeptides 0:135 Post-synthetic modification of an amino-functionalized metal-organic framework for highly efficient enrichment of N-linked glycopeptides. 27186633 1 28 mod modification 266:277 arg1 -NH2 293:296 MIL-101(Cr)-NH2 282:296 MIL-101(Cr)-NH2 282:296 A maltose-functionalized metal-organic framework (MOF), MIL-101(Cr)-maltose, was developed via a simple two step post-synthetic modification of MIL-101(Cr)-NH2. 27186633 1 28 mod modification 266:277 arg3 step 246:249 a simple two step post-synthetic modification 233:277 a simple two step post-synthetic modification of MIL-101(Cr)-NH2 233:296 A maltose-functionalized metal-organic framework (MOF), MIL-101(Cr)-maltose, was developed via a simple two step post-synthetic modification of MIL-101(Cr)-NH2. 27186633 1 29 theme metal-organic 163:175 arg1 framework 177:185 A maltose-functionalized metal-organic framework 138:185 A maltose-functionalized metal-organic framework (MOF) 138:191 A maltose-functionalized metal-organic framework (MOF), MIL-101(Cr)-maltose, was developed via a simple two step post-synthetic modification of MIL-101(Cr)-NH2. 27186633 1 29 theme metal-organic 163:175 arg1 MOF 188:190 MOF 188:190 MOF 188:190 A maltose-functionalized metal-organic framework (MOF), MIL-101(Cr)-maltose, was developed via a simple two step post-synthetic modification of MIL-101(Cr)-NH2. 27186633 3 30 from perspective 560:570 arg1 design 584:589 material design 575:589 material design in sample preparation 575:611 More importantly, the generic functionalization route from amino-derived MOFs opens a new perspective in material design in sample preparation. 27186633 1 31 theme simple 235:240 arg1 modification 266:277 a simple two step post-synthetic modification 233:277 a simple two step post-synthetic modification of MIL-101(Cr)-NH2 233:296 A maltose-functionalized metal-organic framework (MOF), MIL-101(Cr)-maltose, was developed via a simple two step post-synthetic modification of MIL-101(Cr)-NH2. 27186633 0 32 theme efficient 90:98 arg1 enrichment 100:109 highly efficient enrichment 83:109 highly efficient enrichment of N-linked glycopeptides 83:135 Post-synthetic modification of an amino-functionalized metal-organic framework for highly efficient enrichment of N-linked glycopeptides. 27186633 2 33 theme nanomaterial 320:331 arg1 use 308:310 the use 304:310 the use of this nanomaterial 304:331 With the use of this nanomaterial, 33 glycopeptides were detected from the digest of human immunoglobulin G, demonstrating its high efficiency in glycoproteomic analysis. 27186633 1 34 theme step 246:249 arg1 modification 266:277 a simple two step post-synthetic modification 233:277 a simple two step post-synthetic modification of MIL-101(Cr)-NH2 233:296 A maltose-functionalized metal-organic framework (MOF), MIL-101(Cr)-maltose, was developed via a simple two step post-synthetic modification of MIL-101(Cr)-NH2. 27168832 5 0 theme sialoglycoprotein 767:783 arg1 D2-40 785:789 the lymphatic endothelium-specific O-linked sialoglycoprotein D2-40 723:789 the lymphatic endothelium-specific O-linked sialoglycoprotein D2-40 723:789 Subsequent immunohistochemical analysis of the lymphatic endothelium-specific O-linked sialoglycoprotein D2-40 confirmed the diagnosis of cystic lymphangioma. 27168832 4 1 theme submucosal 657:666 arg1 dissection 668:677 endoscopic submucosal dissection 646:677 endoscopic submucosal dissection 646:677 The lesion was successfully removed by endoscopic submucosal dissection. 27168832 2 2 theme cystic 274:279 arg1 lymphangioma 281:292 a giant cystic lymphangioma 266:292 a giant cystic lymphangioma originating in the cardia of the stomach 266:333 In the present study, the case of a giant cystic lymphangioma originating in the cardia of the stomach was reported in an 18-year-old female complaining of abdominal distention. 27168832 5 3 theme D2-40 785:789 arg1 analysis 711:718 Subsequent immunohistochemical analysis 680:718 Subsequent immunohistochemical analysis of the lymphatic endothelium-specific O-linked sialoglycoprotein D2-40 680:789 Subsequent immunohistochemical analysis of the lymphatic endothelium-specific O-linked sialoglycoprotein D2-40 confirmed the diagnosis of cystic lymphangioma. 27168832 2 4 theme giant 268:272 arg1 lymphangioma 281:292 a giant cystic lymphangioma 266:292 a giant cystic lymphangioma originating in the cardia of the stomach 266:333 In the present study, the case of a giant cystic lymphangioma originating in the cardia of the stomach was reported in an 18-year-old female complaining of abdominal distention. 27168832 7 5 theme abdominal 1151:1159 arg1 complaints 1161:1170 aspecific abdominal complaints 1141:1170 aspecific abdominal complaints 1141:1170 The present case demonstrates that a diagnosis of cystic lymphangioma should be considered in non-pediatric patients suffering aspecific abdominal complaints. 27168832 5 6 link O-linked 758:765 arg1 D2-40 785:789 the lymphatic endothelium-specific O-linked sialoglycoprotein D2-40 723:789 the lymphatic endothelium-specific O-linked sialoglycoprotein D2-40 723:789 Subsequent immunohistochemical analysis of the lymphatic endothelium-specific O-linked sialoglycoprotein D2-40 confirmed the diagnosis of cystic lymphangioma. 27168832 0 7 theme case 72:75 arg1 report 77:82 A case report 70:82 A case report 70:82 Giant cystic lymphangioma originating from the cardia of the stomach: A case report. 27168832 7 8 theme aspecific 1141:1149 arg1 complaints 1161:1170 aspecific abdominal complaints 1141:1170 aspecific abdominal complaints 1141:1170 The present case demonstrates that a diagnosis of cystic lymphangioma should be considered in non-pediatric patients suffering aspecific abdominal complaints. 27168832 0 9 theme Giant 0:4 arg1 lymphangioma 13:24 Giant cystic lymphangioma 0:24 Giant cystic lymphangioma originating from the cardia of the stomach 0:67 Giant cystic lymphangioma originating from the cardia of the stomach: A case report. 27168832 3 10 theme Contrast-enhanced 410:426 arg1 tomography 437:446 Contrast-enhanced computed tomography 410:446 Contrast-enhanced computed tomography 410:446 Contrast-enhanced computed tomography and endoscopic ultrasonography revealed a large, multilobulated cystic mass located between the cardia and esophagogastric junction with a diameter of 4.0 cm. 27168832 4 11 theme endoscopic 646:655 arg1 dissection 668:677 endoscopic submucosal dissection 646:677 endoscopic submucosal dissection 646:677 The lesion was successfully removed by endoscopic submucosal dissection. 27168832 7 12 theme non-pediatric 1108:1120 arg1 patients 1122:1129 non-pediatric patients 1108:1129 non-pediatric patients suffering aspecific abdominal complaints 1108:1170 The present case demonstrates that a diagnosis of cystic lymphangioma should be considered in non-pediatric patients suffering aspecific abdominal complaints. 27168832 5 13 theme cystic 818:823 arg1 lymphangioma 825:836 cystic lymphangioma 818:836 cystic lymphangioma 818:836 Subsequent immunohistochemical analysis of the lymphatic endothelium-specific O-linked sialoglycoprotein D2-40 confirmed the diagnosis of cystic lymphangioma. 27168832 0 14 dep report 77:82 arg1 lymphangioma 13:24 Giant cystic lymphangioma 0:24 Giant cystic lymphangioma originating from the cardia of the stomach 0:67 Giant cystic lymphangioma originating from the cardia of the stomach: A case report. 27168832 5 15 theme lymphatic 727:735 arg1 D2-40 785:789 the lymphatic endothelium-specific O-linked sialoglycoprotein D2-40 723:789 the lymphatic endothelium-specific O-linked sialoglycoprotein D2-40 723:789 Subsequent immunohistochemical analysis of the lymphatic endothelium-specific O-linked sialoglycoprotein D2-40 confirmed the diagnosis of cystic lymphangioma. 27168832 3 16 theme large 490:494 arg1 mass 519:522 a large, multilobulated cystic mass 488:522 a large, multilobulated cystic mass located between the cardia and esophagogastric junction with a diameter of 4.0 cm 488:604 Contrast-enhanced computed tomography and endoscopic ultrasonography revealed a large, multilobulated cystic mass located between the cardia and esophagogastric junction with a diameter of 4.0 cm. 27168832 0 17 theme cystic 6:11 arg1 lymphangioma 13:24 Giant cystic lymphangioma 0:24 Giant cystic lymphangioma originating from the cardia of the stomach 0:67 Giant cystic lymphangioma originating from the cardia of the stomach: A case report. 27168832 3 18 with junction 571:578 arg1 diameter 587:594 a diameter 585:594 a diameter of 4.0 cm 585:604 Contrast-enhanced computed tomography and endoscopic ultrasonography revealed a large, multilobulated cystic mass located between the cardia and esophagogastric junction with a diameter of 4.0 cm. 27168832 3 19 theme located 524:530 arg1 mass 519:522 a large, multilobulated cystic mass 488:522 a large, multilobulated cystic mass located between the cardia and esophagogastric junction with a diameter of 4.0 cm 488:604 Contrast-enhanced computed tomography and endoscopic ultrasonography revealed a large, multilobulated cystic mass located between the cardia and esophagogastric junction with a diameter of 4.0 cm. 27168832 2 20 theme 18-year-old 354:364 arg1 female 366:371 an 18-year-old female 351:371 an 18-year-old female complaining of abdominal distention 351:407 In the present study, the case of a giant cystic lymphangioma originating in the cardia of the stomach was reported in an 18-year-old female complaining of abdominal distention. 27168832 6 21 from follow-up 1003:1011 arg1 complaints 946:955 any further complaints 934:955 any further complaints 934:955 No complications associated with the tumor dissection occurred, and the patient did not report any further complaints or any signs of recurrence at 6- and 18-month follow-up. 27168832 6 21 from follow-up 1003:1011 arg1 signs 964:968 any signs 960:968 any signs of recurrence 960:982 No complications associated with the tumor dissection occurred, and the patient did not report any further complaints or any signs of recurrence at 6- and 18-month follow-up. 27168832 5 22 theme lymphangioma 825:836 arg1 diagnosis 805:813 the diagnosis 801:813 the diagnosis of cystic lymphangioma 801:836 Subsequent immunohistochemical analysis of the lymphatic endothelium-specific O-linked sialoglycoprotein D2-40 confirmed the diagnosis of cystic lymphangioma. 27168832 1 23 theme years 225:229 arg1 age 216:218 the age 212:218 the age of 5 years 212:229 Cystic lymphangiomas are rare benign tumors involving the neck, head, and axilla, and most frequently occur in children before the age of 5 years. 27168832 3 24 theme cystic 512:517 arg1 mass 519:522 a large, multilobulated cystic mass 488:522 a large, multilobulated cystic mass located between the cardia and esophagogastric junction with a diameter of 4.0 cm 488:604 Contrast-enhanced computed tomography and endoscopic ultrasonography revealed a large, multilobulated cystic mass located between the cardia and esophagogastric junction with a diameter of 4.0 cm. 27168832 6 25 theme recurrence 973:982 arg1 complaints 946:955 any further complaints 934:955 any further complaints 934:955 No complications associated with the tumor dissection occurred, and the patient did not report any further complaints or any signs of recurrence at 6- and 18-month follow-up. 27168832 6 25 theme recurrence 973:982 arg1 signs 964:968 any signs 960:968 any signs of recurrence 960:982 No complications associated with the tumor dissection occurred, and the patient did not report any further complaints or any signs of recurrence at 6- and 18-month follow-up. 27168832 3 26 theme cm 603:604 arg1 diameter 587:594 a diameter 585:594 a diameter of 4.0 cm 585:604 Contrast-enhanced computed tomography and endoscopic ultrasonography revealed a large, multilobulated cystic mass located between the cardia and esophagogastric junction with a diameter of 4.0 cm. 27168832 1 27 theme Cystic 85:90 arg1 lymphangiomas 92:104 Cystic lymphangiomas 85:104 Cystic lymphangiomas 85:104 Cystic lymphangiomas are rare benign tumors involving the neck, head, and axilla, and most frequently occur in children before the age of 5 years. 27168832 1 27 theme Cystic 85:90 arg1 tumors 122:127 rare benign tumors 110:127 rare benign tumors involving the neck, head, and axilla 110:164 Cystic lymphangiomas are rare benign tumors involving the neck, head, and axilla, and most frequently occur in children before the age of 5 years. 27168832 5 28 theme Subsequent 680:689 arg1 analysis 711:718 Subsequent immunohistochemical analysis 680:718 Subsequent immunohistochemical analysis of the lymphatic endothelium-specific O-linked sialoglycoprotein D2-40 680:789 Subsequent immunohistochemical analysis of the lymphatic endothelium-specific O-linked sialoglycoprotein D2-40 confirmed the diagnosis of cystic lymphangioma. 27168832 5 29 theme endothelium-specific 737:756 arg1 D2-40 785:789 the lymphatic endothelium-specific O-linked sialoglycoprotein D2-40 723:789 the lymphatic endothelium-specific O-linked sialoglycoprotein D2-40 723:789 Subsequent immunohistochemical analysis of the lymphatic endothelium-specific O-linked sialoglycoprotein D2-40 confirmed the diagnosis of cystic lymphangioma. 27168832 2 30 theme stomach 327:333 arg1 cardia 313:318 the cardia 309:318 the cardia of the stomach 309:333 In the present study, the case of a giant cystic lymphangioma originating in the cardia of the stomach was reported in an 18-year-old female complaining of abdominal distention. 27168832 2 31 theme abdominal 388:396 arg1 distention 398:407 abdominal distention 388:407 abdominal distention 388:407 In the present study, the case of a giant cystic lymphangioma originating in the cardia of the stomach was reported in an 18-year-old female complaining of abdominal distention. 27168832 5 32 theme immunohistochemical 691:709 arg1 analysis 711:718 Subsequent immunohistochemical analysis 680:718 Subsequent immunohistochemical analysis of the lymphatic endothelium-specific O-linked sialoglycoprotein D2-40 680:789 Subsequent immunohistochemical analysis of the lymphatic endothelium-specific O-linked sialoglycoprotein D2-40 confirmed the diagnosis of cystic lymphangioma. 27168832 3 33 theme esophagogastric 555:569 arg1 junction 571:578 the cardia and esophagogastric junction 540:578 the cardia and esophagogastric junction with a diameter of 4.0 cm 540:604 Contrast-enhanced computed tomography and endoscopic ultrasonography revealed a large, multilobulated cystic mass located between the cardia and esophagogastric junction with a diameter of 4.0 cm. 27168832 6 34 theme tumor 876:880 arg1 dissection 882:891 the tumor dissection 872:891 the tumor dissection 872:891 No complications associated with the tumor dissection occurred, and the patient did not report any further complaints or any signs of recurrence at 6- and 18-month follow-up. 27168832 3 35 theme computed 428:435 arg1 tomography 437:446 Contrast-enhanced computed tomography 410:446 Contrast-enhanced computed tomography 410:446 Contrast-enhanced computed tomography and endoscopic ultrasonography revealed a large, multilobulated cystic mass located between the cardia and esophagogastric junction with a diameter of 4.0 cm. 27168832 7 36 theme lymphangioma 1071:1082 arg1 diagnosis 1051:1059 a diagnosis 1049:1059 a diagnosis of cystic lymphangioma 1049:1082 The present case demonstrates that a diagnosis of cystic lymphangioma should be considered in non-pediatric patients suffering aspecific abdominal complaints. 27168832 3 37 theme cardia 544:549 arg1 junction 571:578 the cardia and esophagogastric junction 540:578 the cardia and esophagogastric junction with a diameter of 4.0 cm 540:604 Contrast-enhanced computed tomography and endoscopic ultrasonography revealed a large, multilobulated cystic mass located between the cardia and esophagogastric junction with a diameter of 4.0 cm. 27168832 3 38 theme endoscopic 452:461 arg1 ultrasonography 463:477 endoscopic ultrasonography 452:477 endoscopic ultrasonography 452:477 Contrast-enhanced computed tomography and endoscopic ultrasonography revealed a large, multilobulated cystic mass located between the cardia and esophagogastric junction with a diameter of 4.0 cm. 27168832 3 39 dep large 490:494 arg1 multilobulated 497:510 multilobulated 497:510 multilobulated 497:510 Contrast-enhanced computed tomography and endoscopic ultrasonography revealed a large, multilobulated cystic mass located between the cardia and esophagogastric junction with a diameter of 4.0 cm. 27168832 7 40 theme present 1018:1024 arg1 case 1026:1029 The present case 1014:1029 The present case 1014:1029 The present case demonstrates that a diagnosis of cystic lymphangioma should be considered in non-pediatric patients suffering aspecific abdominal complaints. 27168832 1 41 theme rare 110:113 arg1 lymphangiomas 92:104 Cystic lymphangiomas 85:104 Cystic lymphangiomas 85:104 Cystic lymphangiomas are rare benign tumors involving the neck, head, and axilla, and most frequently occur in children before the age of 5 years. 27168832 1 41 theme rare 110:113 arg1 tumors 122:127 rare benign tumors 110:127 rare benign tumors involving the neck, head, and axilla 110:164 Cystic lymphangiomas are rare benign tumors involving the neck, head, and axilla, and most frequently occur in children before the age of 5 years. 27168832 2 42 theme present 239:245 arg1 study 247:251 the present study 235:251 the present study 235:251 In the present study, the case of a giant cystic lymphangioma originating in the cardia of the stomach was reported in an 18-year-old female complaining of abdominal distention. 27168832 5 43 gly sialoglycoprotein 767:783 arg1 sialoglycoprotein 767:783 the lymphatic endothelium-specific O-linked sialoglycoprotein D2-40 723:789 the lymphatic endothelium-specific O-linked sialoglycoprotein D2-40 723:789 Subsequent immunohistochemical analysis of the lymphatic endothelium-specific O-linked sialoglycoprotein D2-40 confirmed the diagnosis of cystic lymphangioma. 27168832 1 44 theme benign 115:120 arg1 lymphangiomas 92:104 Cystic lymphangiomas 85:104 Cystic lymphangiomas 85:104 Cystic lymphangiomas are rare benign tumors involving the neck, head, and axilla, and most frequently occur in children before the age of 5 years. 27168832 1 44 theme benign 115:120 arg1 tumors 122:127 rare benign tumors 110:127 rare benign tumors involving the neck, head, and axilla 110:164 Cystic lymphangiomas are rare benign tumors involving the neck, head, and axilla, and most frequently occur in children before the age of 5 years. 27168832 0 45 theme stomach 61:67 arg1 cardia 47:52 the cardia 43:52 the cardia of the stomach 43:67 Giant cystic lymphangioma originating from the cardia of the stomach: A case report. 27168832 5 46 theme O-linked 758:765 arg1 D2-40 785:789 the lymphatic endothelium-specific O-linked sialoglycoprotein D2-40 723:789 the lymphatic endothelium-specific O-linked sialoglycoprotein D2-40 723:789 Subsequent immunohistochemical analysis of the lymphatic endothelium-specific O-linked sialoglycoprotein D2-40 confirmed the diagnosis of cystic lymphangioma. 27168832 6 47 theme further 938:944 arg1 complaints 946:955 any further complaints 934:955 any further complaints 934:955 No complications associated with the tumor dissection occurred, and the patient did not report any further complaints or any signs of recurrence at 6- and 18-month follow-up. 27168832 7 48 theme cystic 1064:1069 arg1 lymphangioma 1071:1082 cystic lymphangioma 1064:1082 cystic lymphangioma 1064:1082 The present case demonstrates that a diagnosis of cystic lymphangioma should be considered in non-pediatric patients suffering aspecific abdominal complaints. 27168832 2 49 theme lymphangioma 281:292 arg1 case 258:261 the case 254:261 the case of a giant cystic lymphangioma originating in the cardia of the stomach 254:333 In the present study, the case of a giant cystic lymphangioma originating in the cardia of the stomach was reported in an 18-year-old female complaining of abdominal distention. 25053991 10 0 from cells 1548:1552 arg1 regulation 1504:1513 regulation 1504:1513 regulation of STEAP1 expression in prostate cells 1504:1552 In conclusion, these data indicate that STEAP1B2 is overexpressed in neoplastic cells, and PTM may be involved in regulation of STEAP1 expression in prostate cells. 25053991 7 1 theme STEAP1 938:943 arg1 stability 945:953 STEAP1 stability 938:953 STEAP1 stability 938:953 Of note, serum triggered opposite effects in LNCaP and PNT1A in relation to STEAP1 stability, e.g., increasing it in PNT1A and decreasing in LNCaP. 25053991 1 2 theme STEAP1 154:159 arg1 gene 161:164 STEAP1 gene 154:164 STEAP1 gene 154:164 STEAP1 gene is overexpressed in several kinds of tumors, particularly in prostate cancer. 25053991 9 3 dep in 1223:1224 arg1 silico 1226:1231 silico 1226:1231 silico 1226:1231 These PTM are supported through in silico analysis, where several modifications such as N-glycosylation, N-Glycation, Phosphorylation and O-linked β-N-acetylglucosamine, may occur in STEAP1 protein. 25053991 8 4 theme post-translational 1089:1106 arg1 PTM 1123:1125 PTM 1123:1125 PTM 1123:1125 These results suggest that STEAP1 may be regulated by post-transcriptional and post-translational modifications (PTM), which may differ between non-neoplastic and neoplastic cells. 25053991 8 4 theme post-translational 1089:1106 arg1 modifications 1108:1120 post-transcriptional and post-translational modifications 1064:1120 post-transcriptional and post-translational modifications (PTM) 1064:1126 These results suggest that STEAP1 may be regulated by post-transcriptional and post-translational modifications (PTM), which may differ between non-neoplastic and neoplastic cells. 25053991 6 5 theme protein 814:820 arg1 stability 792:800 the stability 788:800 the stability of mRNA and protein 788:820 Regarding STEAP1 regulation, it is demonstrated that the stability of mRNA and protein is higher in LNCaP than in PNT1A cells. 25053991 6 5 theme protein 814:820 arg1 higher 825:830 higher 825:830 higher 825:830 Regarding STEAP1 regulation, it is demonstrated that the stability of mRNA and protein is higher in LNCaP than in PNT1A cells. 25053991 6 6 theme mRNA 805:808 arg1 stability 792:800 the stability 788:800 the stability of mRNA and protein 788:820 Regarding STEAP1 regulation, it is demonstrated that the stability of mRNA and protein is higher in LNCaP than in PNT1A cells. 25053991 6 6 theme mRNA 805:808 arg1 higher 825:830 higher 825:830 higher 825:830 Regarding STEAP1 regulation, it is demonstrated that the stability of mRNA and protein is higher in LNCaP than in PNT1A cells. 25053991 2 7 theme different 321:329 arg1 transcripts 331:341 two different transcripts 317:341 two different transcripts 317:341 Besides STEAP1, there is another related gene, STEAP1B, which may encode two different transcripts. 25053991 2 7 theme different 321:329 arg1 gene 285:288 another related gene 269:288 another related gene 269:288 Besides STEAP1, there is another related gene, STEAP1B, which may encode two different transcripts. 25053991 10 8 theme prostate 1539:1546 arg1 cells 1548:1552 prostate cells 1539:1552 prostate cells 1539:1552 In conclusion, these data indicate that STEAP1B2 is overexpressed in neoplastic cells, and PTM may be involved in regulation of STEAP1 expression in prostate cells. 25053991 0 9 from Expression 0:9 arg1 lines 50:54 prostate cell lines 36:54 prostate cell lines 36:54 Expression of STEAP1 and STEAP1B in prostate cell lines, and the putative regulation of STEAP1 by post-transcriptional and post-translational mechanisms. 25053991 9 10 theme in 1223:1224 arg1 analysis 1233:1240 in silico analysis 1223:1240 in silico analysis 1223:1240 These PTM are supported through in silico analysis, where several modifications such as N-glycosylation, N-Glycation, Phosphorylation and O-linked β-N-acetylglucosamine, may occur in STEAP1 protein. 25053991 2 11 theme related 277:283 arg1 transcripts 331:341 two different transcripts 317:341 two different transcripts 317:341 Besides STEAP1, there is another related gene, STEAP1B, which may encode two different transcripts. 25053991 2 11 theme related 277:283 arg1 STEAP1B 291:297 STEAP1B 291:297 STEAP1B 291:297 Besides STEAP1, there is another related gene, STEAP1B, which may encode two different transcripts. 25053991 2 11 theme related 277:283 arg1 gene 285:288 another related gene 269:288 another related gene 269:288 Besides STEAP1, there is another related gene, STEAP1B, which may encode two different transcripts. 25053991 9 12 theme several 1249:1255 arg1 Phosphorylation 1309:1323 Phosphorylation 1309:1323 Phosphorylation 1309:1323 These PTM are supported through in silico analysis, where several modifications such as N-glycosylation, N-Glycation, Phosphorylation and O-linked β-N-acetylglucosamine, may occur in STEAP1 protein. 25053991 9 12 theme several 1249:1255 arg1 β-N-acetylglucosamine 1338:1358 O-linked β-N-acetylglucosamine 1329:1358 O-linked β-N-acetylglucosamine 1329:1358 These PTM are supported through in silico analysis, where several modifications such as N-glycosylation, N-Glycation, Phosphorylation and O-linked β-N-acetylglucosamine, may occur in STEAP1 protein. 25053991 9 12 theme several 1249:1255 arg1 N-Glycation 1296:1306 N-Glycation 1296:1306 N-Glycation 1296:1306 These PTM are supported through in silico analysis, where several modifications such as N-glycosylation, N-Glycation, Phosphorylation and O-linked β-N-acetylglucosamine, may occur in STEAP1 protein. 25053991 9 12 theme several 1249:1255 arg1 modifications 1257:1269 several modifications 1249:1269 several modifications 1249:1269 These PTM are supported through in silico analysis, where several modifications such as N-glycosylation, N-Glycation, Phosphorylation and O-linked β-N-acetylglucosamine, may occur in STEAP1 protein. 25053991 9 12 theme several 1249:1255 arg1 N-glycosylation 1279:1293 N-glycosylation 1279:1293 N-glycosylation 1279:1293 These PTM are supported through in silico analysis, where several modifications such as N-glycosylation, N-Glycation, Phosphorylation and O-linked β-N-acetylglucosamine, may occur in STEAP1 protein. 25053991 0 13 theme putative 65:72 arg1 regulation 74:83 the putative regulation 61:83 the putative regulation of STEAP1 by post-transcriptional and post-translational mechanisms 61:151 Expression of STEAP1 and STEAP1B in prostate cell lines, and the putative regulation of STEAP1 by post-transcriptional and post-translational mechanisms. 25053991 7 14 from PNT1A 917:921 arg1 relation 926:933 relation 926:933 relation to STEAP1 stability 926:953 Of note, serum triggered opposite effects in LNCaP and PNT1A in relation to STEAP1 stability, e.g., increasing it in PNT1A and decreasing in LNCaP. 25053991 9 15 theme O-linked 1329:1336 arg1 β-N-acetylglucosamine 1338:1358 O-linked β-N-acetylglucosamine 1329:1358 O-linked β-N-acetylglucosamine 1329:1358 These PTM are supported through in silico analysis, where several modifications such as N-glycosylation, N-Glycation, Phosphorylation and O-linked β-N-acetylglucosamine, may occur in STEAP1 protein. 25053991 0 16 theme STEAP1 88:93 arg1 regulation 74:83 the putative regulation 61:83 the putative regulation of STEAP1 by post-transcriptional and post-translational mechanisms 61:151 Expression of STEAP1 and STEAP1B in prostate cell lines, and the putative regulation of STEAP1 by post-transcriptional and post-translational mechanisms. 25053991 0 16 theme STEAP1 88:93 arg1 Expression 0:9 Expression 0:9 Expression of STEAP1 and STEAP1B in prostate cell lines 0:54 Expression of STEAP1 and STEAP1B in prostate cell lines, and the putative regulation of STEAP1 by post-transcriptional and post-translational mechanisms. 25053991 7 17 dep triggered 877:885 arg1 decreasing 989:998 decreasing 989:998 decreasing in LNCaP 989:1007 Of note, serum triggered opposite effects in LNCaP and PNT1A in relation to STEAP1 stability, e.g., increasing it in PNT1A and decreasing in LNCaP. 25053991 7 17 dep triggered 877:885 arg1 increasing 962:971 increasing 962:971 increasing it in PNT1A 962:983 Of note, serum triggered opposite effects in LNCaP and PNT1A in relation to STEAP1 stability, e.g., increasing it in PNT1A and decreasing in LNCaP. 25053991 8 18 theme neoplastic 1173:1182 arg1 cells 1184:1188 non-neoplastic and neoplastic cells 1154:1188 non-neoplastic and neoplastic cells 1154:1188 These results suggest that STEAP1 may be regulated by post-transcriptional and post-translational modifications (PTM), which may differ between non-neoplastic and neoplastic cells. 25053991 4 19 from level 641:645 arg1 differences 615:625 slight differences 608:625 slight differences at structural level 608:645 In silico analysis allowed us to show that STEAP1 and STEAP1B share high homology, but with slight differences at structural level. 25053991 4 20 theme structural 630:639 arg1 level 641:645 structural level 630:645 structural level 630:645 In silico analysis allowed us to show that STEAP1 and STEAP1B share high homology, but with slight differences at structural level. 25053991 6 21 theme PNT1A 849:853 arg1 cells 855:859 PNT1A cells 849:859 PNT1A cells 849:859 Regarding STEAP1 regulation, it is demonstrated that the stability of mRNA and protein is higher in LNCaP than in PNT1A cells. 25053991 3 22 theme putative 400:407 arg1 target 427:432 a putative immunotherapeutic target 398:432 a putative immunotherapeutic target 398:432 Although several studies have been pointing STEAP1 as a putative immunotherapeutic target and biomarker, the mechanisms underlying its regulation are not fully understood. 25053991 3 22 theme putative 400:407 arg1 STEAP1 388:393 STEAP1 388:393 STEAP1 388:393 Although several studies have been pointing STEAP1 as a putative immunotherapeutic target and biomarker, the mechanisms underlying its regulation are not fully understood. 25053991 10 23 theme neoplastic 1459:1468 arg1 cells 1470:1474 neoplastic cells 1459:1474 neoplastic cells 1459:1474 In conclusion, these data indicate that STEAP1B2 is overexpressed in neoplastic cells, and PTM may be involved in regulation of STEAP1 expression in prostate cells. 25053991 4 24 dep In 516:517 arg1 silico 519:524 silico 519:524 silico 519:524 In silico analysis allowed us to show that STEAP1 and STEAP1B share high homology, but with slight differences at structural level. 25053991 3 25 theme immunotherapeutic 409:425 arg1 target 427:432 a putative immunotherapeutic target 398:432 a putative immunotherapeutic target 398:432 Although several studies have been pointing STEAP1 as a putative immunotherapeutic target and biomarker, the mechanisms underlying its regulation are not fully understood. 25053991 3 25 theme immunotherapeutic 409:425 arg1 STEAP1 388:393 STEAP1 388:393 STEAP1 388:393 Although several studies have been pointing STEAP1 as a putative immunotherapeutic target and biomarker, the mechanisms underlying its regulation are not fully understood. 25053991 3 26 theme several 353:359 arg1 studies 361:367 several studies 353:367 several studies 353:367 Although several studies have been pointing STEAP1 as a putative immunotherapeutic target and biomarker, the mechanisms underlying its regulation are not fully understood. 25053991 7 27 theme opposite 887:894 arg1 effects 896:902 opposite effects 887:902 opposite effects 887:902 Of note, serum triggered opposite effects in LNCaP and PNT1A in relation to STEAP1 stability, e.g., increasing it in PNT1A and decreasing in LNCaP. 25053991 0 28 theme post-transcriptional 98:117 arg1 mechanisms 142:151 post-transcriptional and post-translational mechanisms 98:151 post-transcriptional and post-translational mechanisms 98:151 Expression of STEAP1 and STEAP1B in prostate cell lines, and the putative regulation of STEAP1 by post-transcriptional and post-translational mechanisms. 25053991 4 29 theme slight 608:613 arg1 differences 615:625 slight differences 608:625 slight differences at structural level 608:645 In silico analysis allowed us to show that STEAP1 and STEAP1B share high homology, but with slight differences at structural level. 25053991 0 30 theme STEAP1 14:19 arg1 regulation 74:83 the putative regulation 61:83 the putative regulation of STEAP1 by post-transcriptional and post-translational mechanisms 61:151 Expression of STEAP1 and STEAP1B in prostate cell lines, and the putative regulation of STEAP1 by post-transcriptional and post-translational mechanisms. 25053991 0 30 theme STEAP1 14:19 arg1 Expression 0:9 Expression 0:9 Expression of STEAP1 and STEAP1B in prostate cell lines 0:54 Expression of STEAP1 and STEAP1B in prostate cell lines, and the putative regulation of STEAP1 by post-transcriptional and post-translational mechanisms. 25053991 10 31 theme expression 1525:1534 arg1 regulation 1504:1513 regulation 1504:1513 regulation of STEAP1 expression in prostate cells 1504:1552 In conclusion, these data indicate that STEAP1B2 is overexpressed in neoplastic cells, and PTM may be involved in regulation of STEAP1 expression in prostate cells. 25053991 0 32 theme post-translational 123:140 arg1 mechanisms 142:151 post-transcriptional and post-translational mechanisms 98:151 post-transcriptional and post-translational mechanisms 98:151 Expression of STEAP1 and STEAP1B in prostate cell lines, and the putative regulation of STEAP1 by post-transcriptional and post-translational mechanisms. 25053991 1 33 theme several 186:192 arg1 kinds 194:198 several kinds 186:198 several kinds of tumors 186:208 STEAP1 gene is overexpressed in several kinds of tumors, particularly in prostate cancer. 25053991 1 34 theme tumors 203:208 arg1 kinds 194:198 several kinds 186:198 several kinds of tumors 186:208 STEAP1 gene is overexpressed in several kinds of tumors, particularly in prostate cancer. 25053991 0 35 theme STEAP1B 25:31 arg1 regulation 74:83 the putative regulation 61:83 the putative regulation of STEAP1 by post-transcriptional and post-translational mechanisms 61:151 Expression of STEAP1 and STEAP1B in prostate cell lines, and the putative regulation of STEAP1 by post-transcriptional and post-translational mechanisms. 25053991 0 35 theme STEAP1B 25:31 arg1 Expression 0:9 Expression 0:9 Expression of STEAP1 and STEAP1B in prostate cell lines 0:54 Expression of STEAP1 and STEAP1B in prostate cell lines, and the putative regulation of STEAP1 by post-transcriptional and post-translational mechanisms. 25053991 8 36 theme non-neoplastic 1154:1167 arg1 cells 1184:1188 non-neoplastic and neoplastic cells 1154:1188 non-neoplastic and neoplastic cells 1154:1188 These results suggest that STEAP1 may be regulated by post-transcriptional and post-translational modifications (PTM), which may differ between non-neoplastic and neoplastic cells. 25053991 10 37 theme STEAP1 1518:1523 arg1 expression 1525:1534 STEAP1 expression 1518:1534 STEAP1 expression in prostate cells 1518:1552 In conclusion, these data indicate that STEAP1B2 is overexpressed in neoplastic cells, and PTM may be involved in regulation of STEAP1 expression in prostate cells. 25053991 0 38 theme cell 45:48 arg1 lines 50:54 prostate cell lines 36:54 prostate cell lines 36:54 Expression of STEAP1 and STEAP1B in prostate cell lines, and the putative regulation of STEAP1 by post-transcriptional and post-translational mechanisms. 25053991 4 39 theme In 516:517 arg1 analysis 526:533 In silico analysis 516:533 In silico analysis 516:533 In silico analysis allowed us to show that STEAP1 and STEAP1B share high homology, but with slight differences at structural level. 25053991 10 40 from regulation 1504:1513 arg1 cells 1548:1552 prostate cells 1539:1552 prostate cells 1539:1552 In conclusion, these data indicate that STEAP1B2 is overexpressed in neoplastic cells, and PTM may be involved in regulation of STEAP1 expression in prostate cells. 25053991 0 41 theme prostate 36:43 arg1 lines 50:54 prostate cell lines 36:54 prostate cell lines 36:54 Expression of STEAP1 and STEAP1B in prostate cell lines, and the putative regulation of STEAP1 by post-transcriptional and post-translational mechanisms. 25053991 5 42 theme prostate 665:672 arg1 cells 674:678 prostate cells 665:678 prostate cells 665:678 Experiments with prostate cells showed that STEAP1B2 is overexpressed in cancer cells. 25053991 10 43 from expression 1525:1534 arg1 cells 1548:1552 prostate cells 1539:1552 prostate cells 1539:1552 In conclusion, these data indicate that STEAP1B2 is overexpressed in neoplastic cells, and PTM may be involved in regulation of STEAP1 expression in prostate cells. 25053991 6 44 theme STEAP1 745:750 arg1 regulation 752:761 STEAP1 regulation 745:761 STEAP1 regulation 745:761 Regarding STEAP1 regulation, it is demonstrated that the stability of mRNA and protein is higher in LNCaP than in PNT1A cells. 25053991 9 45 link O-linked 1329:1336 arg1 β-N-acetylglucosamine 1338:1358 O-linked β-N-acetylglucosamine 1329:1358 O-linked β-N-acetylglucosamine 1329:1358 These PTM are supported through in silico analysis, where several modifications such as N-glycosylation, N-Glycation, Phosphorylation and O-linked β-N-acetylglucosamine, may occur in STEAP1 protein. 25053991 0 46 from regulation 74:83 arg1 lines 50:54 prostate cell lines 36:54 prostate cell lines 36:54 Expression of STEAP1 and STEAP1B in prostate cell lines, and the putative regulation of STEAP1 by post-transcriptional and post-translational mechanisms. 25053991 7 47 from LNCaP 907:911 arg1 relation 926:933 relation 926:933 relation to STEAP1 stability 926:953 Of note, serum triggered opposite effects in LNCaP and PNT1A in relation to STEAP1 stability, e.g., increasing it in PNT1A and decreasing in LNCaP. 25053991 4 48 theme high 584:587 arg1 homology 589:596 high homology 584:596 high homology 584:596 In silico analysis allowed us to show that STEAP1 and STEAP1B share high homology, but with slight differences at structural level. 25053991 1 49 theme prostate 227:234 arg1 cancer 236:241 prostate cancer 227:241 prostate cancer 227:241 STEAP1 gene is overexpressed in several kinds of tumors, particularly in prostate cancer. 25053991 8 50 theme post-transcriptional 1064:1083 arg1 PTM 1123:1125 PTM 1123:1125 PTM 1123:1125 These results suggest that STEAP1 may be regulated by post-transcriptional and post-translational modifications (PTM), which may differ between non-neoplastic and neoplastic cells. 25053991 8 50 theme post-transcriptional 1064:1083 arg1 modifications 1108:1120 post-transcriptional and post-translational modifications 1064:1120 post-transcriptional and post-translational modifications (PTM) 1064:1126 These results suggest that STEAP1 may be regulated by post-transcriptional and post-translational modifications (PTM), which may differ between non-neoplastic and neoplastic cells. 25053991 9 51 theme STEAP1 1374:1379 arg1 protein 1381:1387 STEAP1 protein 1374:1387 STEAP1 protein 1374:1387 These PTM are supported through in silico analysis, where several modifications such as N-glycosylation, N-Glycation, Phosphorylation and O-linked β-N-acetylglucosamine, may occur in STEAP1 protein. 25053991 5 52 with Experiments 648:658 arg1 cells 674:678 prostate cells 665:678 prostate cells 665:678 Experiments with prostate cells showed that STEAP1B2 is overexpressed in cancer cells. 25053991 5 53 theme cancer 721:726 arg1 cells 728:732 cancer cells 721:732 cancer cells 721:732 Experiments with prostate cells showed that STEAP1B2 is overexpressed in cancer cells. 25433688 4 0 theme other 529:533 arg1 substances 543:552 other foreign substances 529:552 other foreign substances 529:552 Excess labeling reagents and other foreign substances remained at the inlet reservoir. 25433688 8 1 link O-linked 1083:1090 arg1 glycans 1092:1098 O-linked glycans 1083:1098 O-linked glycans chemically released from glycoproteins 1083:1137 Application of the method showed excellent resolution in the analysis of O-linked glycans chemically released from glycoproteins. 25433688 8 2 theme method 1029:1034 arg1 Application 1010:1020 Application 1010:1020 Application of the method 1010:1034 Application of the method showed excellent resolution in the analysis of O-linked glycans chemically released from glycoproteins. 25433688 1 3 theme poly 173:176 arg1 microchip 198:206 a poly(methylmethacrylate) microchip 171:206 a poly(methylmethacrylate) microchip 171:206 A selective separation method using a poly(methylmethacrylate) microchip was developed for 7-amino-4-methylcoumarin-labeled saccharides in a crude reaction mixture. 25433688 0 4 theme mucin-type 68:77 arg1 electrophoresis 39:53 A rapid and highly sensitive microchip electrophoresis 0:53 A rapid and highly sensitive microchip electrophoresis of mono- and mucin-type oligosaccharides 0:94 A rapid and highly sensitive microchip electrophoresis of mono- and mucin-type oligosaccharides labeled with 7-amino-4-methylcoumarin. 25433688 8 5 theme excellent 1043:1051 arg1 resolution 1053:1062 excellent resolution 1043:1062 excellent resolution 1043:1062 Application of the method showed excellent resolution in the analysis of O-linked glycans chemically released from glycoproteins. 25433688 2 6 theme saccharide 330:339 arg1 derivatives 341:351 saccharide derivatives 330:351 saccharide derivatives 330:351 In an alkaline borate buffer, saccharide derivatives formed strong anionic borate complexes. 25433688 4 7 theme labeling 507:514 arg1 reagents 516:523 Excess labeling reagents 500:523 Excess labeling reagents 500:523 Excess labeling reagents and other foreign substances remained at the inlet reservoir. 25433688 6 8 theme detection 804:812 arg1 2 nM 840:843 2 nM 840:843 2 nM 840:843 The lower limit of detection (signal-to-noise = 5) was 2 nM. 25433688 6 8 theme detection 804:812 arg1 limit 795:799 The lower limit 785:799 The lower limit of detection (signal-to-noise = 5) 785:834 The lower limit of detection (signal-to-noise = 5) was 2 nM. 25433688 5 9 theme monosaccharide 657:670 arg1 derivatives 672:682 monosaccharide derivatives 657:682 monosaccharide derivatives 657:682 A confocal fluorimetric detection system enabled the determination of monosaccharide derivatives with good linearity between at least 5 and 100 nM, corresponding to 50 fmol to 1 pmol per injection. 25433688 7 10 theme reported 911:918 arg1 values 920:925 reported values 911:925 reported values using fluorometric detection, capillary electrophoresis, or liquid chromatography 911:1007 The sensitivity and linear quantitation range were comparable to reported values using fluorometric detection, capillary electrophoresis, or liquid chromatography. 25433688 4 11 theme Excess 500:505 arg1 reagents 516:523 Excess labeling reagents 500:523 Excess labeling reagents 500:523 Excess labeling reagents and other foreign substances remained at the inlet reservoir. 25433688 5 12 theme derivatives 672:682 arg1 determination 640:652 the determination 636:652 the determination of monosaccharide derivatives with good linearity between at least 5 and 100 nM 636:732 A confocal fluorimetric detection system enabled the determination of monosaccharide derivatives with good linearity between at least 5 and 100 nM, corresponding to 50 fmol to 1 pmol per injection. 25433688 2 13 theme borate 315:320 arg1 buffer 322:327 an alkaline borate buffer 303:327 an alkaline borate buffer 303:327 In an alkaline borate buffer, saccharide derivatives formed strong anionic borate complexes. 25433688 1 14 theme methylmethacrylate 178:195 arg1 microchip 198:206 a poly(methylmethacrylate) microchip 171:206 a poly(methylmethacrylate) microchip 171:206 A selective separation method using a poly(methylmethacrylate) microchip was developed for 7-amino-4-methylcoumarin-labeled saccharides in a crude reaction mixture. 25433688 5 15 theme good 689:692 arg1 linearity 694:702 good linearity 689:702 good linearity between at least 5 and 100 nM 689:732 A confocal fluorimetric detection system enabled the determination of monosaccharide derivatives with good linearity between at least 5 and 100 nM, corresponding to 50 fmol to 1 pmol per injection. 25433688 5 16 theme detection 611:619 arg1 system 621:626 A confocal fluorimetric detection system 587:626 A confocal fluorimetric detection system 587:626 A confocal fluorimetric detection system enabled the determination of monosaccharide derivatives with good linearity between at least 5 and 100 nM, corresponding to 50 fmol to 1 pmol per injection. 25433688 2 17 theme alkaline 306:313 arg1 buffer 322:327 an alkaline borate buffer 303:327 an alkaline borate buffer 303:327 In an alkaline borate buffer, saccharide derivatives formed strong anionic borate complexes. 25433688 8 18 attach released 1111:1118 arg2 glycans 1092:1098 O-linked glycans 1083:1098 O-linked glycans chemically released from glycoproteins 1083:1137 Application of the method showed excellent resolution in the analysis of O-linked glycans chemically released from glycoproteins. 25433688 8 18 attach released 1111:1118 arg1 glycoproteins 1125:1137 glycoproteins 1125:1137 glycoproteins 1125:1137 Application of the method showed excellent resolution in the analysis of O-linked glycans chemically released from glycoproteins. 25433688 0 19 theme rapid 2:6 arg1 electrophoresis 39:53 A rapid and highly sensitive microchip electrophoresis 0:53 A rapid and highly sensitive microchip electrophoresis of mono- and mucin-type oligosaccharides 0:94 A rapid and highly sensitive microchip electrophoresis of mono- and mucin-type oligosaccharides labeled with 7-amino-4-methylcoumarin. 25433688 2 20 theme strong 360:365 arg1 complexes 382:390 strong anionic borate complexes 360:390 strong anionic borate complexes 360:390 In an alkaline borate buffer, saccharide derivatives formed strong anionic borate complexes. 25433688 7 21 theme liquid 987:992 arg1 chromatography 994:1007 liquid chromatography 987:1007 liquid chromatography 987:1007 The sensitivity and linear quantitation range were comparable to reported values using fluorometric detection, capillary electrophoresis, or liquid chromatography. 25433688 8 22 theme glycans 1092:1098 arg1 analysis 1071:1078 the analysis 1067:1078 the analysis of O-linked glycans chemically released from glycoproteins 1067:1137 Application of the method showed excellent resolution in the analysis of O-linked glycans chemically released from glycoproteins. 25433688 8 23 theme O-linked 1083:1090 arg1 glycans 1092:1098 O-linked glycans 1083:1098 O-linked glycans chemically released from glycoproteins 1083:1137 Application of the method showed excellent resolution in the analysis of O-linked glycans chemically released from glycoproteins. 25433688 0 24 dep mono- 58:62 arg1 oligosaccharides 79:94 oligosaccharides 79:94 oligosaccharides 79:94 A rapid and highly sensitive microchip electrophoresis of mono- and mucin-type oligosaccharides labeled with 7-amino-4-methylcoumarin. 25433688 7 25 theme linear 866:871 arg1 range 886:890 linear quantitation range 866:890 linear quantitation range 866:890 The sensitivity and linear quantitation range were comparable to reported values using fluorometric detection, capillary electrophoresis, or liquid chromatography. 25433688 0 26 theme microchip 29:37 arg1 electrophoresis 39:53 A rapid and highly sensitive microchip electrophoresis 0:53 A rapid and highly sensitive microchip electrophoresis of mono- and mucin-type oligosaccharides 0:94 A rapid and highly sensitive microchip electrophoresis of mono- and mucin-type oligosaccharides labeled with 7-amino-4-methylcoumarin. 25433688 7 27 theme quantitation 873:884 arg1 range 886:890 linear quantitation range 866:890 linear quantitation range 866:890 The sensitivity and linear quantitation range were comparable to reported values using fluorometric detection, capillary electrophoresis, or liquid chromatography. 25433688 1 28 theme 7-amino-4-methylcoumarin-labeled 226:257 arg1 saccharides 259:269 7-amino-4-methylcoumarin-labeled saccharides 226:269 7-amino-4-methylcoumarin-labeled saccharides in a crude reaction mixture 226:297 A selective separation method using a poly(methylmethacrylate) microchip was developed for 7-amino-4-methylcoumarin-labeled saccharides in a crude reaction mixture. 25433688 0 29 theme sensitive 19:27 arg1 electrophoresis 39:53 A rapid and highly sensitive microchip electrophoresis 0:53 A rapid and highly sensitive microchip electrophoresis of mono- and mucin-type oligosaccharides 0:94 A rapid and highly sensitive microchip electrophoresis of mono- and mucin-type oligosaccharides labeled with 7-amino-4-methylcoumarin. 25433688 3 30 theme electric 451:458 arg1 field 460:464 an electric field 448:464 an electric field 448:464 These complexes moved from the cathode to the anode in an electric field and were detected near the anode. 25433688 1 31 from saccharides 259:269 arg1 mixture 291:297 a crude reaction mixture 274:297 a crude reaction mixture 274:297 A selective separation method using a poly(methylmethacrylate) microchip was developed for 7-amino-4-methylcoumarin-labeled saccharides in a crude reaction mixture. 25433688 5 32 with determination 640:652 arg1 linearity 694:702 good linearity 689:702 good linearity between at least 5 and 100 nM 689:732 A confocal fluorimetric detection system enabled the determination of monosaccharide derivatives with good linearity between at least 5 and 100 nM, corresponding to 50 fmol to 1 pmol per injection. 25433688 4 33 theme foreign 535:541 arg1 substances 543:552 other foreign substances 529:552 other foreign substances 529:552 Excess labeling reagents and other foreign substances remained at the inlet reservoir. 25433688 5 34 theme confocal 589:596 arg1 system 621:626 A confocal fluorimetric detection system 587:626 A confocal fluorimetric detection system 587:626 A confocal fluorimetric detection system enabled the determination of monosaccharide derivatives with good linearity between at least 5 and 100 nM, corresponding to 50 fmol to 1 pmol per injection. 25433688 1 35 theme selective 137:145 arg1 method 158:163 A selective separation method 135:163 A selective separation method using a poly(methylmethacrylate) microchip 135:206 A selective separation method using a poly(methylmethacrylate) microchip was developed for 7-amino-4-methylcoumarin-labeled saccharides in a crude reaction mixture. 25433688 4 36 theme inlet 570:574 arg1 reservoir 576:584 the inlet reservoir 566:584 the inlet reservoir 566:584 Excess labeling reagents and other foreign substances remained at the inlet reservoir. 25433688 5 37 theme fluorimetric 598:609 arg1 system 621:626 A confocal fluorimetric detection system 587:626 A confocal fluorimetric detection system 587:626 A confocal fluorimetric detection system enabled the determination of monosaccharide derivatives with good linearity between at least 5 and 100 nM, corresponding to 50 fmol to 1 pmol per injection. 25433688 1 38 theme separation 147:156 arg1 method 158:163 A selective separation method 135:163 A selective separation method using a poly(methylmethacrylate) microchip 135:206 A selective separation method using a poly(methylmethacrylate) microchip was developed for 7-amino-4-methylcoumarin-labeled saccharides in a crude reaction mixture. 25433688 6 39 theme lower 789:793 arg1 2 nM 840:843 2 nM 840:843 2 nM 840:843 The lower limit of detection (signal-to-noise = 5) was 2 nM. 25433688 6 39 theme lower 789:793 arg1 limit 795:799 The lower limit 785:799 The lower limit of detection (signal-to-noise = 5) 785:834 The lower limit of detection (signal-to-noise = 5) was 2 nM. 25433688 2 40 theme anionic 367:373 arg1 complexes 382:390 strong anionic borate complexes 360:390 strong anionic borate complexes 360:390 In an alkaline borate buffer, saccharide derivatives formed strong anionic borate complexes. 25433688 7 41 theme capillary 957:965 arg1 electrophoresis 967:981 capillary electrophoresis 957:981 capillary electrophoresis 957:981 The sensitivity and linear quantitation range were comparable to reported values using fluorometric detection, capillary electrophoresis, or liquid chromatography. 25433688 2 42 theme borate 375:380 arg1 complexes 382:390 strong anionic borate complexes 360:390 strong anionic borate complexes 360:390 In an alkaline borate buffer, saccharide derivatives formed strong anionic borate complexes. 25433688 7 43 theme fluorometric 933:944 arg1 detection 946:954 fluorometric detection 933:954 fluorometric detection 933:954 The sensitivity and linear quantitation range were comparable to reported values using fluorometric detection, capillary electrophoresis, or liquid chromatography. 25433688 8 44 gly glycoproteins 1125:1137 arg1 glycoproteins 1125:1137 glycoproteins 1125:1137 glycoproteins 1125:1137 Application of the method showed excellent resolution in the analysis of O-linked glycans chemically released from glycoproteins. 25433688 1 45 theme crude 276:280 arg1 mixture 291:297 a crude reaction mixture 274:297 a crude reaction mixture 274:297 A selective separation method using a poly(methylmethacrylate) microchip was developed for 7-amino-4-methylcoumarin-labeled saccharides in a crude reaction mixture. 25433688 0 46 theme mono- 58:62 arg1 electrophoresis 39:53 A rapid and highly sensitive microchip electrophoresis 0:53 A rapid and highly sensitive microchip electrophoresis of mono- and mucin-type oligosaccharides 0:94 A rapid and highly sensitive microchip electrophoresis of mono- and mucin-type oligosaccharides labeled with 7-amino-4-methylcoumarin. 25433688 3 47 from anode 439:443 arg1 field 460:464 an electric field 448:464 an electric field 448:464 These complexes moved from the cathode to the anode in an electric field and were detected near the anode. 25433688 1 48 theme reaction 282:289 arg1 mixture 291:297 a crude reaction mixture 274:297 a crude reaction mixture 274:297 A selective separation method using a poly(methylmethacrylate) microchip was developed for 7-amino-4-methylcoumarin-labeled saccharides in a crude reaction mixture. 27832720 1 0 theme 1,2-α-l-fucosidase 267:284 arg1 engineering 252:262 protein engineering 244:262 protein engineering of 1,2-α-l-fucosidase from Bifidobacterium bifidum JCM 1254 244:322 We have recently generated a highly efficient 1,2-α-l-fucosynthase (BbAfcA N423H mutant) by protein engineering of 1,2-α-l-fucosidase from Bifidobacterium bifidum JCM 1254. 27832720 4 1 theme application 747:757 arg1 study 759:763 This application study 742:763 This application study 742:763 This application study broadens the feasibility of this novel H-antigen synthesis technique in functional glycomics. 27832720 4 2 theme H-antigen 804:812 arg1 technique 824:832 this novel H-antigen synthesis technique 793:832 this novel H-antigen synthesis technique 793:832 This application study broadens the feasibility of this novel H-antigen synthesis technique in functional glycomics. 27832720 1 3 theme Bifidobacterium 291:305 arg1 JCM 315:317 Bifidobacterium bifidum JCM 1254 291:322 Bifidobacterium bifidum JCM 1254 291:322 We have recently generated a highly efficient 1,2-α-l-fucosynthase (BbAfcA N423H mutant) by protein engineering of 1,2-α-l-fucosidase from Bifidobacterium bifidum JCM 1254. 27832720 3 4 theme Fuc 618:620 arg1 residues 622:629 insert Fuc residues 611:629 insert Fuc residues 611:629 In the present study, we show an extended application of the engineered 1,2-α-l-fucosynthase by demonstrating its ability to insert Fuc residues into N- and O-glycans in fetuin glycoproteins, GM1 ganglioside, and a plant-derived xyloglucan nonasaccharide. 27832720 4 5 theme technique 824:832 arg1 feasibility 778:788 the feasibility 774:788 the feasibility of this novel H-antigen synthesis technique in functional glycomics 774:856 This application study broadens the feasibility of this novel H-antigen synthesis technique in functional glycomics. 27832720 1 6 theme bifidum 307:313 arg1 JCM 315:317 Bifidobacterium bifidum JCM 1254 291:322 Bifidobacterium bifidum JCM 1254 291:322 We have recently generated a highly efficient 1,2-α-l-fucosynthase (BbAfcA N423H mutant) by protein engineering of 1,2-α-l-fucosidase from Bifidobacterium bifidum JCM 1254. 27832720 4 7 theme novel 798:802 arg1 technique 824:832 this novel H-antigen synthesis technique 793:832 this novel H-antigen synthesis technique 793:832 This application study broadens the feasibility of this novel H-antigen synthesis technique in functional glycomics. 27832720 0 8 from introduction 43:54 arg1 ganglioside 107:117 ganglioside 107:117 ganglioside 107:117 Application study of 1,2-α-l-fucosynthase: introduction of Fucα1-2Gal disaccharide structures on N-glycan, ganglioside, and xyloglucan oligosaccharide. 27832720 0 8 from introduction 43:54 arg1 xyloglucan 124:133 xyloglucan 124:133 xyloglucan 124:133 Application study of 1,2-α-l-fucosynthase: introduction of Fucα1-2Gal disaccharide structures on N-glycan, ganglioside, and xyloglucan oligosaccharide. 27832720 0 8 from introduction 43:54 arg1 N-glycan 97:104 N-glycan 97:104 N-glycan 97:104 Application study of 1,2-α-l-fucosynthase: introduction of Fucα1-2Gal disaccharide structures on N-glycan, ganglioside, and xyloglucan oligosaccharide. 27832720 4 9 theme functional 837:846 arg1 glycomics 848:856 functional glycomics 837:856 functional glycomics 837:856 This application study broadens the feasibility of this novel H-antigen synthesis technique in functional glycomics. 27832720 1 10 theme efficient 188:196 arg1 1,2-α-l-fucosynthase 198:217 a highly efficient 1,2-α-l-fucosynthase 179:217 a highly efficient 1,2-α-l-fucosynthase (BbAfcA N423H mutant) 179:239 We have recently generated a highly efficient 1,2-α-l-fucosynthase (BbAfcA N423H mutant) by protein engineering of 1,2-α-l-fucosidase from Bifidobacterium bifidum JCM 1254. 27832720 1 11 from JCM 315:317 arg1 engineering 252:262 protein engineering 244:262 protein engineering of 1,2-α-l-fucosidase from Bifidobacterium bifidum JCM 1254 244:322 We have recently generated a highly efficient 1,2-α-l-fucosynthase (BbAfcA N423H mutant) by protein engineering of 1,2-α-l-fucosidase from Bifidobacterium bifidum JCM 1254. 27832720 1 11 from JCM 315:317 arg1 1,2-α-l-fucosidase 267:284 1,2-α-l-fucosidase 267:284 1,2-α-l-fucosidase from Bifidobacterium bifidum JCM 1254 267:322 We have recently generated a highly efficient 1,2-α-l-fucosynthase (BbAfcA N423H mutant) by protein engineering of 1,2-α-l-fucosidase from Bifidobacterium bifidum JCM 1254. 27832720 0 12 dep N-glycan 97:104 arg1 oligosaccharide 135:149 oligosaccharide 135:149 oligosaccharide 135:149 Application study of 1,2-α-l-fucosynthase: introduction of Fucα1-2Gal disaccharide structures on N-glycan, ganglioside, and xyloglucan oligosaccharide. 27832720 2 13 theme oligosaccharides 422:437 arg1 ends 414:417 the non-reducing ends 397:417 the non-reducing ends of oligosaccharides 397:437 This synthase could specifically introduce H-antigens (Fucα1-2Gal) into the non-reducing ends of oligosaccharides and in O-linked glycans in mucin glycoprotein. 27832720 0 14 theme Application 0:10 arg1 study 12:16 Application study 0:16 Application study of 1,2-α-l-fucosynthase: introduction of Fucα1-2Gal disaccharide structures on N-glycan, ganglioside, and xyloglucan oligosaccharide. 0:150 Application study of 1,2-α-l-fucosynthase: introduction of Fucα1-2Gal disaccharide structures on N-glycan, ganglioside, and xyloglucan oligosaccharide. 27832720 0 15 theme 1,2-α-l-fucosynthase 21:40 arg1 study 12:16 Application study 0:16 Application study of 1,2-α-l-fucosynthase: introduction of Fucα1-2Gal disaccharide structures on N-glycan, ganglioside, and xyloglucan oligosaccharide. 0:150 Application study of 1,2-α-l-fucosynthase: introduction of Fucα1-2Gal disaccharide structures on N-glycan, ganglioside, and xyloglucan oligosaccharide. 27832720 0 16 dep study 12:16 arg1 introduction 43:54 introduction 43:54 Application study of 1,2-α-l-fucosynthase: introduction of Fucα1-2Gal disaccharide structures on N-glycan, ganglioside, and xyloglucan oligosaccharide. 0:150 Application study of 1,2-α-l-fucosynthase: introduction of Fucα1-2Gal disaccharide structures on N-glycan, ganglioside, and xyloglucan oligosaccharide. 27832720 4 17 theme synthesis 814:822 arg1 technique 824:832 this novel H-antigen synthesis technique 793:832 this novel H-antigen synthesis technique 793:832 This application study broadens the feasibility of this novel H-antigen synthesis technique in functional glycomics. 27832720 3 18 from N- 636:637 arg1 glycoproteins 663:675 fetuin glycoproteins 656:675 fetuin glycoproteins 656:675 In the present study, we show an extended application of the engineered 1,2-α-l-fucosynthase by demonstrating its ability to insert Fuc residues into N- and O-glycans in fetuin glycoproteins, GM1 ganglioside, and a plant-derived xyloglucan nonasaccharide. 27832720 3 18 from N- 636:637 arg1 ganglioside 682:692 GM1 ganglioside 678:692 GM1 ganglioside 678:692 In the present study, we show an extended application of the engineered 1,2-α-l-fucosynthase by demonstrating its ability to insert Fuc residues into N- and O-glycans in fetuin glycoproteins, GM1 ganglioside, and a plant-derived xyloglucan nonasaccharide. 27832720 3 18 from N- 636:637 arg1 nonasaccharide 726:739 a plant-derived xyloglucan nonasaccharide 699:739 a plant-derived xyloglucan nonasaccharide 699:739 In the present study, we show an extended application of the engineered 1,2-α-l-fucosynthase by demonstrating its ability to insert Fuc residues into N- and O-glycans in fetuin glycoproteins, GM1 ganglioside, and a plant-derived xyloglucan nonasaccharide. 27832720 2 19 theme mucin 466:470 arg1 glycoprotein 472:483 mucin glycoprotein 466:483 mucin glycoprotein 466:483 This synthase could specifically introduce H-antigens (Fucα1-2Gal) into the non-reducing ends of oligosaccharides and in O-linked glycans in mucin glycoprotein. 27832720 0 20 from N-glycan 97:104 arg1 introduction 43:54 introduction 43:54 Application study of 1,2-α-l-fucosynthase: introduction of Fucα1-2Gal disaccharide structures on N-glycan, ganglioside, and xyloglucan oligosaccharide. 0:150 Application study of 1,2-α-l-fucosynthase: introduction of Fucα1-2Gal disaccharide structures on N-glycan, ganglioside, and xyloglucan oligosaccharide. 27832720 3 21 theme insert 611:616 arg1 residues 622:629 insert Fuc residues 611:629 insert Fuc residues 611:629 In the present study, we show an extended application of the engineered 1,2-α-l-fucosynthase by demonstrating its ability to insert Fuc residues into N- and O-glycans in fetuin glycoproteins, GM1 ganglioside, and a plant-derived xyloglucan nonasaccharide. 27832720 1 22 dep 1,2-α-l-fucosynthase 198:217 arg1 N423H 227:231 N423H 227:231 N423H 227:231 We have recently generated a highly efficient 1,2-α-l-fucosynthase (BbAfcA N423H mutant) by protein engineering of 1,2-α-l-fucosidase from Bifidobacterium bifidum JCM 1254. 27832720 3 23 from O-glycans 643:651 arg1 glycoproteins 663:675 fetuin glycoproteins 656:675 fetuin glycoproteins 656:675 In the present study, we show an extended application of the engineered 1,2-α-l-fucosynthase by demonstrating its ability to insert Fuc residues into N- and O-glycans in fetuin glycoproteins, GM1 ganglioside, and a plant-derived xyloglucan nonasaccharide. 27832720 3 23 from O-glycans 643:651 arg1 ganglioside 682:692 GM1 ganglioside 678:692 GM1 ganglioside 678:692 In the present study, we show an extended application of the engineered 1,2-α-l-fucosynthase by demonstrating its ability to insert Fuc residues into N- and O-glycans in fetuin glycoproteins, GM1 ganglioside, and a plant-derived xyloglucan nonasaccharide. 27832720 3 23 from O-glycans 643:651 arg1 nonasaccharide 726:739 a plant-derived xyloglucan nonasaccharide 699:739 a plant-derived xyloglucan nonasaccharide 699:739 In the present study, we show an extended application of the engineered 1,2-α-l-fucosynthase by demonstrating its ability to insert Fuc residues into N- and O-glycans in fetuin glycoproteins, GM1 ganglioside, and a plant-derived xyloglucan nonasaccharide. 27832720 3 24 theme present 493:499 arg1 study 501:505 the present study 489:505 the present study 489:505 In the present study, we show an extended application of the engineered 1,2-α-l-fucosynthase by demonstrating its ability to insert Fuc residues into N- and O-glycans in fetuin glycoproteins, GM1 ganglioside, and a plant-derived xyloglucan nonasaccharide. 27832720 0 25 from structures 83:92 arg1 ganglioside 107:117 ganglioside 107:117 ganglioside 107:117 Application study of 1,2-α-l-fucosynthase: introduction of Fucα1-2Gal disaccharide structures on N-glycan, ganglioside, and xyloglucan oligosaccharide. 27832720 0 25 from structures 83:92 arg1 xyloglucan 124:133 xyloglucan 124:133 xyloglucan 124:133 Application study of 1,2-α-l-fucosynthase: introduction of Fucα1-2Gal disaccharide structures on N-glycan, ganglioside, and xyloglucan oligosaccharide. 27832720 0 25 from structures 83:92 arg1 N-glycan 97:104 N-glycan 97:104 N-glycan 97:104 Application study of 1,2-α-l-fucosynthase: introduction of Fucα1-2Gal disaccharide structures on N-glycan, ganglioside, and xyloglucan oligosaccharide. 27832720 2 26 theme O-linked 446:453 arg1 glycans 455:461 O-linked glycans 446:461 O-linked glycans in mucin glycoprotein 446:483 This synthase could specifically introduce H-antigens (Fucα1-2Gal) into the non-reducing ends of oligosaccharides and in O-linked glycans in mucin glycoprotein. 27832720 0 27 theme Fucα1-2Gal 59:68 arg1 structures 83:92 Fucα1-2Gal disaccharide structures 59:92 Fucα1-2Gal disaccharide structures on N-glycan, ganglioside, and xyloglucan oligosaccharide 59:149 Application study of 1,2-α-l-fucosynthase: introduction of Fucα1-2Gal disaccharide structures on N-glycan, ganglioside, and xyloglucan oligosaccharide. 27832720 1 28 from engineering 252:262 arg1 JCM 315:317 Bifidobacterium bifidum JCM 1254 291:322 Bifidobacterium bifidum JCM 1254 291:322 We have recently generated a highly efficient 1,2-α-l-fucosynthase (BbAfcA N423H mutant) by protein engineering of 1,2-α-l-fucosidase from Bifidobacterium bifidum JCM 1254. 27832720 4 29 from feasibility 778:788 arg1 glycomics 848:856 functional glycomics 837:856 functional glycomics 837:856 This application study broadens the feasibility of this novel H-antigen synthesis technique in functional glycomics. 27832720 3 30 theme extended 519:526 arg1 application 528:538 an extended application 516:538 an extended application of the engineered 1,2-α-l-fucosynthase 516:577 In the present study, we show an extended application of the engineered 1,2-α-l-fucosynthase by demonstrating its ability to insert Fuc residues into N- and O-glycans in fetuin glycoproteins, GM1 ganglioside, and a plant-derived xyloglucan nonasaccharide. 27832720 3 31 theme xyloglucan 715:724 arg1 nonasaccharide 726:739 a plant-derived xyloglucan nonasaccharide 699:739 a plant-derived xyloglucan nonasaccharide 699:739 In the present study, we show an extended application of the engineered 1,2-α-l-fucosynthase by demonstrating its ability to insert Fuc residues into N- and O-glycans in fetuin glycoproteins, GM1 ganglioside, and a plant-derived xyloglucan nonasaccharide. 27832720 3 32 theme GM1 678:680 arg1 ganglioside 682:692 GM1 ganglioside 678:692 GM1 ganglioside 678:692 In the present study, we show an extended application of the engineered 1,2-α-l-fucosynthase by demonstrating its ability to insert Fuc residues into N- and O-glycans in fetuin glycoproteins, GM1 ganglioside, and a plant-derived xyloglucan nonasaccharide. 27832720 2 33 link O-linked 446:453 arg1 glycans 455:461 O-linked glycans 446:461 O-linked glycans in mucin glycoprotein 446:483 This synthase could specifically introduce H-antigens (Fucα1-2Gal) into the non-reducing ends of oligosaccharides and in O-linked glycans in mucin glycoprotein. 27832720 3 34 link plant-derived 701:713 arg1 nonasaccharide 726:739 a plant-derived xyloglucan nonasaccharide 699:739 a plant-derived xyloglucan nonasaccharide 699:739 In the present study, we show an extended application of the engineered 1,2-α-l-fucosynthase by demonstrating its ability to insert Fuc residues into N- and O-glycans in fetuin glycoproteins, GM1 ganglioside, and a plant-derived xyloglucan nonasaccharide. 27832720 0 35 from ganglioside 107:117 arg1 introduction 43:54 introduction 43:54 Application study of 1,2-α-l-fucosynthase: introduction of Fucα1-2Gal disaccharide structures on N-glycan, ganglioside, and xyloglucan oligosaccharide. 0:150 Application study of 1,2-α-l-fucosynthase: introduction of Fucα1-2Gal disaccharide structures on N-glycan, ganglioside, and xyloglucan oligosaccharide. 27832720 2 36 from glycans 455:461 arg1 glycoprotein 472:483 mucin glycoprotein 466:483 mucin glycoprotein 466:483 This synthase could specifically introduce H-antigens (Fucα1-2Gal) into the non-reducing ends of oligosaccharides and in O-linked glycans in mucin glycoprotein. 27832720 3 37 theme 1,2-α-l-fucosynthase 558:577 arg1 application 528:538 an extended application 516:538 an extended application of the engineered 1,2-α-l-fucosynthase 516:577 In the present study, we show an extended application of the engineered 1,2-α-l-fucosynthase by demonstrating its ability to insert Fuc residues into N- and O-glycans in fetuin glycoproteins, GM1 ganglioside, and a plant-derived xyloglucan nonasaccharide. 27832720 1 38 theme protein 244:250 arg1 engineering 252:262 protein engineering 244:262 protein engineering of 1,2-α-l-fucosidase from Bifidobacterium bifidum JCM 1254 244:322 We have recently generated a highly efficient 1,2-α-l-fucosynthase (BbAfcA N423H mutant) by protein engineering of 1,2-α-l-fucosidase from Bifidobacterium bifidum JCM 1254. 27832720 0 39 theme structures 83:92 arg1 introduction 43:54 introduction 43:54 Application study of 1,2-α-l-fucosynthase: introduction of Fucα1-2Gal disaccharide structures on N-glycan, ganglioside, and xyloglucan oligosaccharide. 0:150 Application study of 1,2-α-l-fucosynthase: introduction of Fucα1-2Gal disaccharide structures on N-glycan, ganglioside, and xyloglucan oligosaccharide. 27832720 3 40 theme plant-derived 701:713 arg1 nonasaccharide 726:739 a plant-derived xyloglucan nonasaccharide 699:739 a plant-derived xyloglucan nonasaccharide 699:739 In the present study, we show an extended application of the engineered 1,2-α-l-fucosynthase by demonstrating its ability to insert Fuc residues into N- and O-glycans in fetuin glycoproteins, GM1 ganglioside, and a plant-derived xyloglucan nonasaccharide. 27832720 2 41 gly glycoprotein 472:483 arg1 glycoprotein 472:483 mucin glycoprotein 466:483 mucin glycoprotein 466:483 This synthase could specifically introduce H-antigens (Fucα1-2Gal) into the non-reducing ends of oligosaccharides and in O-linked glycans in mucin glycoprotein. 27832720 3 42 theme engineered 547:556 arg1 1,2-α-l-fucosynthase 558:577 the engineered 1,2-α-l-fucosynthase 543:577 the engineered 1,2-α-l-fucosynthase 543:577 In the present study, we show an extended application of the engineered 1,2-α-l-fucosynthase by demonstrating its ability to insert Fuc residues into N- and O-glycans in fetuin glycoproteins, GM1 ganglioside, and a plant-derived xyloglucan nonasaccharide. 27832720 3 43 gly glycoproteins 663:675 arg1 glycoproteins 663:675 fetuin glycoproteins 656:675 fetuin glycoproteins 656:675 In the present study, we show an extended application of the engineered 1,2-α-l-fucosynthase by demonstrating its ability to insert Fuc residues into N- and O-glycans in fetuin glycoproteins, GM1 ganglioside, and a plant-derived xyloglucan nonasaccharide. 27832720 0 44 theme disaccharide 70:81 arg1 structures 83:92 Fucα1-2Gal disaccharide structures 59:92 Fucα1-2Gal disaccharide structures on N-glycan, ganglioside, and xyloglucan oligosaccharide 59:149 Application study of 1,2-α-l-fucosynthase: introduction of Fucα1-2Gal disaccharide structures on N-glycan, ganglioside, and xyloglucan oligosaccharide. 27832720 3 45 theme fetuin 656:661 arg1 glycoproteins 663:675 fetuin glycoproteins 656:675 fetuin glycoproteins 656:675 In the present study, we show an extended application of the engineered 1,2-α-l-fucosynthase by demonstrating its ability to insert Fuc residues into N- and O-glycans in fetuin glycoproteins, GM1 ganglioside, and a plant-derived xyloglucan nonasaccharide. 27832720 2 46 theme non-reducing 401:412 arg1 ends 414:417 the non-reducing ends 397:417 the non-reducing ends of oligosaccharides 397:437 This synthase could specifically introduce H-antigens (Fucα1-2Gal) into the non-reducing ends of oligosaccharides and in O-linked glycans in mucin glycoprotein. 27832720 0 47 from xyloglucan 124:133 arg1 introduction 43:54 introduction 43:54 Application study of 1,2-α-l-fucosynthase: introduction of Fucα1-2Gal disaccharide structures on N-glycan, ganglioside, and xyloglucan oligosaccharide. 0:150 Application study of 1,2-α-l-fucosynthase: introduction of Fucα1-2Gal disaccharide structures on N-glycan, ganglioside, and xyloglucan oligosaccharide. 25892842 0 0 theme O-glycans 67:75 arg1 sialylation 16:26 sialylation 16:26 sialylation 16:26 The analysis of sialylation, N-glycan branching, and expression of O-glycans in seminal plasma of infertile men. 25892842 0 0 theme O-glycans 67:75 arg1 branching 38:46 N-glycan branching 29:46 N-glycan branching 29:46 The analysis of sialylation, N-glycan branching, and expression of O-glycans in seminal plasma of infertile men. 25892842 0 0 theme O-glycans 67:75 arg1 expression 53:62 expression 53:62 expression of O-glycans in seminal plasma of infertile men 53:110 The analysis of sialylation, N-glycan branching, and expression of O-glycans in seminal plasma of infertile men. 25892842 3 1 from traits 430:435 arg1 glycoproteins 455:467 seminal plasma glycoproteins 440:467 seminal plasma glycoproteins of fertile and infertile men 440:496 In this work we aimed to compare some glycosylation traits in seminal plasma glycoproteins of fertile and infertile men. 25892842 3 2 theme men 494:496 arg1 glycoproteins 455:467 seminal plasma glycoproteins 440:467 seminal plasma glycoproteins of fertile and infertile men 440:496 In this work we aimed to compare some glycosylation traits in seminal plasma glycoproteins of fertile and infertile men. 25892842 4 3 theme oligozoospermic 881:895 arg1 patients 897:904 oligozoospermic patients 881:904 oligozoospermic patients 881:904 The following findings emerge from our studies: (1) in human seminal plasma the presence and alterations of O-linked glycans were observed; (2) the expression of SNA-reactive sialic acid significantly differs between asthenozoospermia and both normozoospermic (fertile and infertile) groups; (3) the expression of PHA-L-reactive highly branched N-glycans was significantly lower in oligozoospermic patients than in both normozoospermic groups. 25892842 0 4 from analysis 4:11 arg1 plasma 88:93 seminal plasma 80:93 seminal plasma of infertile men 80:110 The analysis of sialylation, N-glycan branching, and expression of O-glycans in seminal plasma of infertile men. 25892842 4 5 theme PHA-L-reactive 813:826 arg1 N-glycans 844:852 PHA-L-reactive highly branched N-glycans 813:852 PHA-L-reactive highly branched N-glycans 813:852 The following findings emerge from our studies: (1) in human seminal plasma the presence and alterations of O-linked glycans were observed; (2) the expression of SNA-reactive sialic acid significantly differs between asthenozoospermia and both normozoospermic (fertile and infertile) groups; (3) the expression of PHA-L-reactive highly branched N-glycans was significantly lower in oligozoospermic patients than in both normozoospermic groups. 25892842 5 6 theme profile 1048:1054 arg1 determination 1020:1032 the possibly precise determination 999:1032 the possibly precise determination of the glycan profile 999:1054 Indication of the appropriate lectins that would enable the possibly precise determination of the glycan profile seems to be a good supplement to mass spectrum analysis. 25892842 5 7 theme appropriate 961:971 arg1 lectins 973:979 the appropriate lectins 957:979 the appropriate lectins that would enable the possibly precise determination of the glycan profile 957:1054 Indication of the appropriate lectins that would enable the possibly precise determination of the glycan profile seems to be a good supplement to mass spectrum analysis. 25892842 0 8 theme seminal 80:86 arg1 plasma 88:93 seminal plasma 80:93 seminal plasma of infertile men 80:110 The analysis of sialylation, N-glycan branching, and expression of O-glycans in seminal plasma of infertile men. 25892842 4 9 link O-linked 607:614 arg1 glycans 616:622 O-linked glycans 607:622 O-linked glycans 607:622 The following findings emerge from our studies: (1) in human seminal plasma the presence and alterations of O-linked glycans were observed; (2) the expression of SNA-reactive sialic acid significantly differs between asthenozoospermia and both normozoospermic (fertile and infertile) groups; (3) the expression of PHA-L-reactive highly branched N-glycans was significantly lower in oligozoospermic patients than in both normozoospermic groups. 25892842 4 10 theme N-glycans 844:852 arg1 expression 799:808 the expression 795:808 (3) the expression of PHA-L-reactive highly branched N-glycans 791:852 The following findings emerge from our studies: (1) in human seminal plasma the presence and alterations of O-linked glycans were observed; (2) the expression of SNA-reactive sialic acid significantly differs between asthenozoospermia and both normozoospermic (fertile and infertile) groups; (3) the expression of PHA-L-reactive highly branched N-glycans was significantly lower in oligozoospermic patients than in both normozoospermic groups. 25892842 4 10 theme N-glycans 844:852 arg1 lower 872:876 lower 872:876 lower 872:876 The following findings emerge from our studies: (1) in human seminal plasma the presence and alterations of O-linked glycans were observed; (2) the expression of SNA-reactive sialic acid significantly differs between asthenozoospermia and both normozoospermic (fertile and infertile) groups; (3) the expression of PHA-L-reactive highly branched N-glycans was significantly lower in oligozoospermic patients than in both normozoospermic groups. 25892842 4 11 dep expression 647:656 arg1 2 640:640 2 640:640 2 640:640 The following findings emerge from our studies: (1) in human seminal plasma the presence and alterations of O-linked glycans were observed; (2) the expression of SNA-reactive sialic acid significantly differs between asthenozoospermia and both normozoospermic (fertile and infertile) groups; (3) the expression of PHA-L-reactive highly branched N-glycans was significantly lower in oligozoospermic patients than in both normozoospermic groups. 25892842 4 12 theme seminal 560:566 arg1 plasma 568:573 human seminal plasma 554:573 human seminal plasma 554:573 The following findings emerge from our studies: (1) in human seminal plasma the presence and alterations of O-linked glycans were observed; (2) the expression of SNA-reactive sialic acid significantly differs between asthenozoospermia and both normozoospermic (fertile and infertile) groups; (3) the expression of PHA-L-reactive highly branched N-glycans was significantly lower in oligozoospermic patients than in both normozoospermic groups. 25892842 5 13 theme good 1070:1073 arg1 supplement 1075:1084 a good supplement 1068:1084 a good supplement to mass spectrum analysis 1068:1110 Indication of the appropriate lectins that would enable the possibly precise determination of the glycan profile seems to be a good supplement to mass spectrum analysis. 25892842 5 13 theme good 1070:1073 arg1 Indication 943:952 Indication 943:952 Indication of the appropriate lectins that would enable the possibly precise determination of the glycan profile 943:1054 Indication of the appropriate lectins that would enable the possibly precise determination of the glycan profile seems to be a good supplement to mass spectrum analysis. 25892842 4 14 theme branched 835:842 arg1 N-glycans 844:852 PHA-L-reactive highly branched N-glycans 813:852 PHA-L-reactive highly branched N-glycans 813:852 The following findings emerge from our studies: (1) in human seminal plasma the presence and alterations of O-linked glycans were observed; (2) the expression of SNA-reactive sialic acid significantly differs between asthenozoospermia and both normozoospermic (fertile and infertile) groups; (3) the expression of PHA-L-reactive highly branched N-glycans was significantly lower in oligozoospermic patients than in both normozoospermic groups. 25892842 5 15 theme lectins 973:979 arg1 supplement 1075:1084 a good supplement 1068:1084 a good supplement to mass spectrum analysis 1068:1110 Indication of the appropriate lectins that would enable the possibly precise determination of the glycan profile seems to be a good supplement to mass spectrum analysis. 25892842 5 15 theme lectins 973:979 arg1 Indication 943:952 Indication 943:952 Indication of the appropriate lectins that would enable the possibly precise determination of the glycan profile 943:1054 Indication of the appropriate lectins that would enable the possibly precise determination of the glycan profile seems to be a good supplement to mass spectrum analysis. 25892842 2 16 from studies 212:218 arg1 glycosylation 227:239 the glycosylation 223:239 the glycosylation of seminal plasma proteins 223:266 Although some studies on the glycosylation of seminal plasma proteins are available, the total glycan profile was rarely analyzed as a feature influencing fertilization potential. 25892842 4 17 theme human 554:558 arg1 plasma 568:573 human seminal plasma 554:573 human seminal plasma 554:573 The following findings emerge from our studies: (1) in human seminal plasma the presence and alterations of O-linked glycans were observed; (2) the expression of SNA-reactive sialic acid significantly differs between asthenozoospermia and both normozoospermic (fertile and infertile) groups; (3) the expression of PHA-L-reactive highly branched N-glycans was significantly lower in oligozoospermic patients than in both normozoospermic groups. 25892842 0 18 from branching 38:46 arg1 plasma 88:93 seminal plasma 80:93 seminal plasma of infertile men 80:110 The analysis of sialylation, N-glycan branching, and expression of O-glycans in seminal plasma of infertile men. 25892842 3 19 theme glycosylation 416:428 arg1 traits 430:435 some glycosylation traits 411:435 some glycosylation traits in seminal plasma glycoproteins of fertile and infertile men 411:496 In this work we aimed to compare some glycosylation traits in seminal plasma glycoproteins of fertile and infertile men. 25892842 2 20 theme proteins 259:266 arg1 glycosylation 227:239 the glycosylation 223:239 the glycosylation of seminal plasma proteins 223:266 Although some studies on the glycosylation of seminal plasma proteins are available, the total glycan profile was rarely analyzed as a feature influencing fertilization potential. 25892842 5 21 theme mass 1089:1092 arg1 analysis 1103:1110 mass spectrum analysis 1089:1110 mass spectrum analysis 1089:1110 Indication of the appropriate lectins that would enable the possibly precise determination of the glycan profile seems to be a good supplement to mass spectrum analysis. 25892842 6 22 theme panel 1137:1141 arg1 Extension 1113:1121 Extension 1113:1121 Extension of the lectin panel 1113:1141 Extension of the lectin panel is useful for the further research. 25892842 4 23 theme following 503:511 arg1 findings 513:520 The following findings 499:520 The following findings 499:520 The following findings emerge from our studies: (1) in human seminal plasma the presence and alterations of O-linked glycans were observed; (2) the expression of SNA-reactive sialic acid significantly differs between asthenozoospermia and both normozoospermic (fertile and infertile) groups; (3) the expression of PHA-L-reactive highly branched N-glycans was significantly lower in oligozoospermic patients than in both normozoospermic groups. 25892842 4 24 theme sialic 674:679 arg1 acid 681:684 SNA-reactive sialic acid 661:684 SNA-reactive sialic acid 661:684 The following findings emerge from our studies: (1) in human seminal plasma the presence and alterations of O-linked glycans were observed; (2) the expression of SNA-reactive sialic acid significantly differs between asthenozoospermia and both normozoospermic (fertile and infertile) groups; (3) the expression of PHA-L-reactive highly branched N-glycans was significantly lower in oligozoospermic patients than in both normozoospermic groups. 25892842 2 25 theme glycan 293:298 arg1 feature 333:339 a feature 331:339 a feature influencing fertilization potential 331:375 Although some studies on the glycosylation of seminal plasma proteins are available, the total glycan profile was rarely analyzed as a feature influencing fertilization potential. 25892842 2 25 theme glycan 293:298 arg1 profile 300:306 the total glycan profile 283:306 the total glycan profile 283:306 Although some studies on the glycosylation of seminal plasma proteins are available, the total glycan profile was rarely analyzed as a feature influencing fertilization potential. 25892842 2 26 gly glycosylation 227:239 arg1 proteins 259:266 seminal plasma proteins 244:266 seminal plasma proteins 244:266 Although some studies on the glycosylation of seminal plasma proteins are available, the total glycan profile was rarely analyzed as a feature influencing fertilization potential. 25892842 0 27 theme men 108:110 arg1 plasma 88:93 seminal plasma 80:93 seminal plasma of infertile men 80:110 The analysis of sialylation, N-glycan branching, and expression of O-glycans in seminal plasma of infertile men. 25892842 2 28 theme total 287:291 arg1 feature 333:339 a feature 331:339 a feature influencing fertilization potential 331:375 Although some studies on the glycosylation of seminal plasma proteins are available, the total glycan profile was rarely analyzed as a feature influencing fertilization potential. 25892842 2 28 theme total 287:291 arg1 profile 300:306 the total glycan profile 283:306 the total glycan profile 283:306 Although some studies on the glycosylation of seminal plasma proteins are available, the total glycan profile was rarely analyzed as a feature influencing fertilization potential. 25892842 1 29 theme successful 172:181 arg1 fertilization 183:195 successful fertilization 172:195 successful fertilization 172:195 Carbohydrates are known to mediate some events involved in successful fertilization. 25892842 6 30 theme lectin 1130:1135 arg1 panel 1137:1141 the lectin panel 1126:1141 the lectin panel 1126:1141 Extension of the lectin panel is useful for the further research. 25892842 0 31 theme infertile 98:106 arg1 men 108:110 infertile men 98:110 infertile men 98:110 The analysis of sialylation, N-glycan branching, and expression of O-glycans in seminal plasma of infertile men. 25892842 0 32 theme N-glycan 29:36 arg1 branching 38:46 N-glycan branching 29:46 N-glycan branching 29:46 The analysis of sialylation, N-glycan branching, and expression of O-glycans in seminal plasma of infertile men. 25892842 4 33 located observed 629:636 arg2 alterations 592:602 alterations 592:602 alterations of O-linked glycans 592:622 The following findings emerge from our studies: (1) in human seminal plasma the presence and alterations of O-linked glycans were observed; (2) the expression of SNA-reactive sialic acid significantly differs between asthenozoospermia and both normozoospermic (fertile and infertile) groups; (3) the expression of PHA-L-reactive highly branched N-glycans was significantly lower in oligozoospermic patients than in both normozoospermic groups. 25892842 4 33 located observed 629:636 arg2 presence 579:586 the presence 575:586 the presence 575:586 The following findings emerge from our studies: (1) in human seminal plasma the presence and alterations of O-linked glycans were observed; (2) the expression of SNA-reactive sialic acid significantly differs between asthenozoospermia and both normozoospermic (fertile and infertile) groups; (3) the expression of PHA-L-reactive highly branched N-glycans was significantly lower in oligozoospermic patients than in both normozoospermic groups. 25892842 4 33 located observed 629:636 arg1 plasma 568:573 human seminal plasma 554:573 human seminal plasma 554:573 The following findings emerge from our studies: (1) in human seminal plasma the presence and alterations of O-linked glycans were observed; (2) the expression of SNA-reactive sialic acid significantly differs between asthenozoospermia and both normozoospermic (fertile and infertile) groups; (3) the expression of PHA-L-reactive highly branched N-glycans was significantly lower in oligozoospermic patients than in both normozoospermic groups. 25892842 3 34 gly glycoproteins 455:467 arg1 glycoproteins 455:467 seminal plasma glycoproteins 440:467 seminal plasma glycoproteins of fertile and infertile men 440:496 In this work we aimed to compare some glycosylation traits in seminal plasma glycoproteins of fertile and infertile men. 25892842 4 35 theme glycans 616:622 arg1 alterations 592:602 alterations 592:602 alterations of O-linked glycans 592:622 The following findings emerge from our studies: (1) in human seminal plasma the presence and alterations of O-linked glycans were observed; (2) the expression of SNA-reactive sialic acid significantly differs between asthenozoospermia and both normozoospermic (fertile and infertile) groups; (3) the expression of PHA-L-reactive highly branched N-glycans was significantly lower in oligozoospermic patients than in both normozoospermic groups. 25892842 4 35 theme glycans 616:622 arg1 presence 579:586 the presence 575:586 the presence 575:586 The following findings emerge from our studies: (1) in human seminal plasma the presence and alterations of O-linked glycans were observed; (2) the expression of SNA-reactive sialic acid significantly differs between asthenozoospermia and both normozoospermic (fertile and infertile) groups; (3) the expression of PHA-L-reactive highly branched N-glycans was significantly lower in oligozoospermic patients than in both normozoospermic groups. 25892842 0 36 from expression 53:62 arg1 plasma 88:93 seminal plasma 80:93 seminal plasma of infertile men 80:110 The analysis of sialylation, N-glycan branching, and expression of O-glycans in seminal plasma of infertile men. 25892842 0 37 theme sialylation 16:26 arg1 analysis 4:11 The analysis 0:11 The analysis of sialylation, N-glycan branching, and expression of O-glycans in seminal plasma of infertile men. 0:111 The analysis of sialylation, N-glycan branching, and expression of O-glycans in seminal plasma of infertile men. 25892842 3 38 theme seminal 440:446 arg1 glycoproteins 455:467 seminal plasma glycoproteins 440:467 seminal plasma glycoproteins of fertile and infertile men 440:496 In this work we aimed to compare some glycosylation traits in seminal plasma glycoproteins of fertile and infertile men. 25892842 4 39 theme normozoospermic 919:933 arg1 groups 935:940 both normozoospermic groups 914:940 both normozoospermic groups 914:940 The following findings emerge from our studies: (1) in human seminal plasma the presence and alterations of O-linked glycans were observed; (2) the expression of SNA-reactive sialic acid significantly differs between asthenozoospermia and both normozoospermic (fertile and infertile) groups; (3) the expression of PHA-L-reactive highly branched N-glycans was significantly lower in oligozoospermic patients than in both normozoospermic groups. 25892842 5 40 theme precise 1012:1018 arg1 determination 1020:1032 the possibly precise determination 999:1032 the possibly precise determination of the glycan profile 999:1054 Indication of the appropriate lectins that would enable the possibly precise determination of the glycan profile seems to be a good supplement to mass spectrum analysis. 25892842 4 41 theme SNA-reactive 661:672 arg1 acid 681:684 SNA-reactive sialic acid 661:684 SNA-reactive sialic acid 661:684 The following findings emerge from our studies: (1) in human seminal plasma the presence and alterations of O-linked glycans were observed; (2) the expression of SNA-reactive sialic acid significantly differs between asthenozoospermia and both normozoospermic (fertile and infertile) groups; (3) the expression of PHA-L-reactive highly branched N-glycans was significantly lower in oligozoospermic patients than in both normozoospermic groups. 25892842 0 42 theme branching 38:46 arg1 analysis 4:11 The analysis 0:11 The analysis of sialylation, N-glycan branching, and expression of O-glycans in seminal plasma of infertile men. 0:111 The analysis of sialylation, N-glycan branching, and expression of O-glycans in seminal plasma of infertile men. 25892842 5 43 theme spectrum 1094:1101 arg1 analysis 1103:1110 mass spectrum analysis 1089:1110 mass spectrum analysis 1089:1110 Indication of the appropriate lectins that would enable the possibly precise determination of the glycan profile seems to be a good supplement to mass spectrum analysis. 25892842 0 44 gly sialylation 16:26 arg1 O-glycans 67:75 O-glycans 67:75 O-glycans 67:75 The analysis of sialylation, N-glycan branching, and expression of O-glycans in seminal plasma of infertile men. 25892842 0 44 gly sialylation 16:26 arg1 plasma 88:93 seminal plasma 80:93 seminal plasma of infertile men 80:110 The analysis of sialylation, N-glycan branching, and expression of O-glycans in seminal plasma of infertile men. 25892842 3 45 theme infertile 484:492 arg1 men 494:496 fertile and infertile men 472:496 fertile and infertile men 472:496 In this work we aimed to compare some glycosylation traits in seminal plasma glycoproteins of fertile and infertile men. 25892842 0 46 from plasma 88:93 arg1 analysis 4:11 The analysis 0:11 The analysis of sialylation, N-glycan branching, and expression of O-glycans in seminal plasma of infertile men. 0:111 The analysis of sialylation, N-glycan branching, and expression of O-glycans in seminal plasma of infertile men. 25892842 2 47 theme plasma 252:257 arg1 proteins 259:266 seminal plasma proteins 244:266 seminal plasma proteins 244:266 Although some studies on the glycosylation of seminal plasma proteins are available, the total glycan profile was rarely analyzed as a feature influencing fertilization potential. 25892842 4 48 theme acid 681:684 arg1 expression 647:656 the expression 643:656 (2) the expression of SNA-reactive sialic acid 639:684 The following findings emerge from our studies: (1) in human seminal plasma the presence and alterations of O-linked glycans were observed; (2) the expression of SNA-reactive sialic acid significantly differs between asthenozoospermia and both normozoospermic (fertile and infertile) groups; (3) the expression of PHA-L-reactive highly branched N-glycans was significantly lower in oligozoospermic patients than in both normozoospermic groups. 25892842 4 49 theme normozoospermic 743:757 arg1 groups 783:788 both normozoospermic (fertile and infertile) groups 738:788 both normozoospermic (fertile and infertile) groups 738:788 The following findings emerge from our studies: (1) in human seminal plasma the presence and alterations of O-linked glycans were observed; (2) the expression of SNA-reactive sialic acid significantly differs between asthenozoospermia and both normozoospermic (fertile and infertile) groups; (3) the expression of PHA-L-reactive highly branched N-glycans was significantly lower in oligozoospermic patients than in both normozoospermic groups. 25892842 5 50 theme glycan 1041:1046 arg1 profile 1048:1054 the glycan profile 1037:1054 the glycan profile 1037:1054 Indication of the appropriate lectins that would enable the possibly precise determination of the glycan profile seems to be a good supplement to mass spectrum analysis. 25892842 2 51 theme seminal 244:250 arg1 proteins 259:266 seminal plasma proteins 244:266 seminal plasma proteins 244:266 Although some studies on the glycosylation of seminal plasma proteins are available, the total glycan profile was rarely analyzed as a feature influencing fertilization potential. 25892842 3 52 theme fertile 472:478 arg1 men 494:496 fertile and infertile men 472:496 fertile and infertile men 472:496 In this work we aimed to compare some glycosylation traits in seminal plasma glycoproteins of fertile and infertile men. 25892842 0 53 theme expression 53:62 arg1 analysis 4:11 The analysis 0:11 The analysis of sialylation, N-glycan branching, and expression of O-glycans in seminal plasma of infertile men. 0:111 The analysis of sialylation, N-glycan branching, and expression of O-glycans in seminal plasma of infertile men. 25892842 4 54 theme O-linked 607:614 arg1 glycans 616:622 O-linked glycans 607:622 O-linked glycans 607:622 The following findings emerge from our studies: (1) in human seminal plasma the presence and alterations of O-linked glycans were observed; (2) the expression of SNA-reactive sialic acid significantly differs between asthenozoospermia and both normozoospermic (fertile and infertile) groups; (3) the expression of PHA-L-reactive highly branched N-glycans was significantly lower in oligozoospermic patients than in both normozoospermic groups. 25892842 4 55 dep observed 629:636 arg1 1 548:548 1 548:548 1 548:548 The following findings emerge from our studies: (1) in human seminal plasma the presence and alterations of O-linked glycans were observed; (2) the expression of SNA-reactive sialic acid significantly differs between asthenozoospermia and both normozoospermic (fertile and infertile) groups; (3) the expression of PHA-L-reactive highly branched N-glycans was significantly lower in oligozoospermic patients than in both normozoospermic groups. 25892842 3 56 theme plasma 448:453 arg1 glycoproteins 455:467 seminal plasma glycoproteins 440:467 seminal plasma glycoproteins of fertile and infertile men 440:496 In this work we aimed to compare some glycosylation traits in seminal plasma glycoproteins of fertile and infertile men. 25892842 2 57 theme fertilization 353:365 arg1 potential 367:375 fertilization potential 353:375 fertilization potential 353:375 Although some studies on the glycosylation of seminal plasma proteins are available, the total glycan profile was rarely analyzed as a feature influencing fertilization potential. 25892842 4 58 dep expression 799:808 arg1 3 792:792 3 792:792 3 792:792 The following findings emerge from our studies: (1) in human seminal plasma the presence and alterations of O-linked glycans were observed; (2) the expression of SNA-reactive sialic acid significantly differs between asthenozoospermia and both normozoospermic (fertile and infertile) groups; (3) the expression of PHA-L-reactive highly branched N-glycans was significantly lower in oligozoospermic patients than in both normozoospermic groups. 25892842 0 59 from sialylation 16:26 arg1 plasma 88:93 seminal plasma 80:93 seminal plasma of infertile men 80:110 The analysis of sialylation, N-glycan branching, and expression of O-glycans in seminal plasma of infertile men. 25892842 6 60 theme further 1161:1167 arg1 research 1169:1176 the further research 1157:1176 the further research 1157:1176 Extension of the lectin panel is useful for the further research. 25892842 4 61 dep normozoospermic 743:757 arg1 infertile 772:780 infertile 772:780 infertile 772:780 The following findings emerge from our studies: (1) in human seminal plasma the presence and alterations of O-linked glycans were observed; (2) the expression of SNA-reactive sialic acid significantly differs between asthenozoospermia and both normozoospermic (fertile and infertile) groups; (3) the expression of PHA-L-reactive highly branched N-glycans was significantly lower in oligozoospermic patients than in both normozoospermic groups. 25892842 4 61 dep normozoospermic 743:757 arg1 fertile 760:766 fertile 760:766 fertile 760:766 The following findings emerge from our studies: (1) in human seminal plasma the presence and alterations of O-linked glycans were observed; (2) the expression of SNA-reactive sialic acid significantly differs between asthenozoospermia and both normozoospermic (fertile and infertile) groups; (3) the expression of PHA-L-reactive highly branched N-glycans was significantly lower in oligozoospermic patients than in both normozoospermic groups. 25808083 10 0 theme protein 1337:1343 arg1 role 1324:1327 the physiological role 1306:1327 the physiological role of this protein 1306:1343 The relative balance of IGF-dependent and IGF-independent actions of IGFBP-6 in vivo together with the related question regarding the roles of IGFBP-6 binding to IGF and non-IGF ligands are keys to understanding the physiological role of this protein. 25808083 10 1 theme IGFBP-6 1237:1243 arg1 binding 1245:1251 IGFBP-6 binding 1237:1251 IGFBP-6 binding to IGF and non-IGF ligands 1237:1278 The relative balance of IGF-dependent and IGF-independent actions of IGFBP-6 in vivo together with the related question regarding the roles of IGFBP-6 binding to IGF and non-IGF ligands are keys to understanding the physiological role of this protein. 25808083 3 2 from promotion 350:358 arg1 cells 381:385 some cells 376:385 some cells 376:385 IGFBP-6 has recently been shown to have a number of IGF-independent actions, including promotion of apoptosis in some cells and inhibition of angiogenesis. 25808083 10 3 theme relative 1098:1105 arg1 balance 1107:1113 The relative balance 1094:1113 The relative balance of IGF-dependent and IGF-independent actions of IGFBP-6 in vivo together with the related question regarding the roles of IGFBP-6 binding to IGF and non-IGF ligands 1094:1278 The relative balance of IGF-dependent and IGF-independent actions of IGFBP-6 in vivo together with the related question regarding the roles of IGFBP-6 binding to IGF and non-IGF ligands are keys to understanding the physiological role of this protein. 25808083 10 3 theme relative 1098:1105 arg1 keys 1284:1287 keys 1284:1287 keys 1284:1287 The relative balance of IGF-dependent and IGF-independent actions of IGFBP-6 in vivo together with the related question regarding the roles of IGFBP-6 binding to IGF and non-IGF ligands are keys to understanding the physiological role of this protein. 25808083 10 4 theme binding 1245:1251 arg1 roles 1228:1232 the roles 1224:1232 the roles of IGFBP-6 binding to IGF and non-IGF ligands 1224:1278 The relative balance of IGF-dependent and IGF-independent actions of IGFBP-6 in vivo together with the related question regarding the roles of IGFBP-6 binding to IGF and non-IGF ligands are keys to understanding the physiological role of this protein. 25808083 10 5 theme related 1197:1203 arg1 question 1205:1212 the related question 1193:1212 the related question regarding the roles of IGFBP-6 binding to IGF and non-IGF ligands 1193:1278 The relative balance of IGF-dependent and IGF-independent actions of IGFBP-6 in vivo together with the related question regarding the roles of IGFBP-6 binding to IGF and non-IGF ligands are keys to understanding the physiological role of this protein. 25808083 4 6 theme IGF-independent 500:514 arg1 mechanism 516:524 an IGF-independent mechanism 497:524 an IGF-independent mechanism 497:524 IGFBP-6 also induces migration of tumour cells including rhabdomyosarcomas by an IGF-independent mechanism. 25808083 9 7 theme cancers 988:994 arg1 number 978:983 a smaller number 968:983 a smaller number 968:983 IGFBP-6 expression is increased in a smaller number of cancers, which may reflect a compensatory mechanism to control IGF-II actions or IGF-independent actions. 25808083 6 8 theme cell 616:619 arg1 surface 621:627 the cell surface 612:627 the cell surface 612:627 IGFBP-6 binds to prohibitin-2 on the cell surface and the latter is required for IGFBP-6-induced migration by a mechanism that is independent of MAP kinases. 25808083 1 9 link O-linked 59:66 arg1 IGFBP-6 45:51 IGFBP-6 45:51 IGFBP-6 45:51 IGFBP-6 is an O-linked glycoprotein that preferentially binds IGF-II over IGF-I. 25808083 1 9 link O-linked 59:66 arg1 glycoprotein 68:79 an O-linked glycoprotein 56:79 an O-linked glycoprotein that preferentially binds IGF-II over IGF-I 56:123 IGFBP-6 is an O-linked glycoprotein that preferentially binds IGF-II over IGF-I. 25808083 4 10 theme cells 460:464 arg1 migration 440:448 migration 440:448 migration of tumour cells including rhabdomyosarcomas 440:492 IGFBP-6 also induces migration of tumour cells including rhabdomyosarcomas by an IGF-independent mechanism. 25808083 8 11 theme cells 869:873 arg1 number 852:857 a number 850:857 a number of cancer cells 850:873 IGFBP-6 expression is decreased in a number of cancer cells and it has been postulated to act as a tumour suppressor. 25808083 3 12 theme IGF-independent 315:329 arg1 actions 331:337 IGF-independent actions 315:337 IGF-independent actions 315:337 IGFBP-6 has recently been shown to have a number of IGF-independent actions, including promotion of apoptosis in some cells and inhibition of angiogenesis. 25808083 3 12 theme IGF-independent 315:329 arg1 promotion 350:358 promotion 350:358 promotion of apoptosis in some cells 350:385 IGFBP-6 has recently been shown to have a number of IGF-independent actions, including promotion of apoptosis in some cells and inhibition of angiogenesis. 25808083 3 12 theme IGF-independent 315:329 arg1 inhibition 391:400 inhibition 391:400 inhibition of angiogenesis 391:416 IGFBP-6 has recently been shown to have a number of IGF-independent actions, including promotion of apoptosis in some cells and inhibition of angiogenesis. 25808083 4 13 theme tumour 453:458 arg1 cells 460:464 tumour cells 453:464 tumour cells 453:464 IGFBP-6 also induces migration of tumour cells including rhabdomyosarcomas by an IGF-independent mechanism. 25808083 9 14 theme compensatory 1017:1028 arg1 mechanism 1030:1038 a compensatory mechanism 1015:1038 a compensatory mechanism to control IGF-II actions or IGF-independent actions 1015:1091 IGFBP-6 expression is increased in a smaller number of cancers, which may reflect a compensatory mechanism to control IGF-II actions or IGF-independent actions. 25808083 8 15 theme cancer 862:867 arg1 cells 869:873 cancer cells 862:873 cancer cells 862:873 IGFBP-6 expression is decreased in a number of cancer cells and it has been postulated to act as a tumour suppressor. 25808083 3 16 theme actions 331:337 arg1 number 305:310 a number 303:310 a number of IGF-independent actions, including promotion of apoptosis in some cells and inhibition of angiogenesis 303:416 IGFBP-6 has recently been shown to have a number of IGF-independent actions, including promotion of apoptosis in some cells and inhibition of angiogenesis. 25808083 3 16 theme actions 331:337 arg1 promotion 350:358 promotion 350:358 promotion of apoptosis in some cells 350:385 IGFBP-6 has recently been shown to have a number of IGF-independent actions, including promotion of apoptosis in some cells and inhibition of angiogenesis. 25808083 3 16 theme actions 331:337 arg1 inhibition 391:400 inhibition 391:400 inhibition of angiogenesis 391:416 IGFBP-6 has recently been shown to have a number of IGF-independent actions, including promotion of apoptosis in some cells and inhibition of angiogenesis. 25808083 1 17 theme O-linked 59:66 arg1 IGFBP-6 45:51 IGFBP-6 45:51 IGFBP-6 45:51 IGFBP-6 is an O-linked glycoprotein that preferentially binds IGF-II over IGF-I. 25808083 1 17 theme O-linked 59:66 arg1 glycoprotein 68:79 an O-linked glycoprotein 56:79 an O-linked glycoprotein that preferentially binds IGF-II over IGF-I 56:123 IGFBP-6 is an O-linked glycoprotein that preferentially binds IGF-II over IGF-I. 25808083 10 18 theme non-IGF 1264:1270 arg1 ligands 1272:1278 IGF and non-IGF ligands 1256:1278 IGF and non-IGF ligands 1256:1278 The relative balance of IGF-dependent and IGF-independent actions of IGFBP-6 in vivo together with the related question regarding the roles of IGFBP-6 binding to IGF and non-IGF ligands are keys to understanding the physiological role of this protein. 25808083 9 19 theme IGFBP-6 933:939 arg1 expression 941:950 IGFBP-6 expression 933:950 IGFBP-6 expression 933:950 IGFBP-6 expression is increased in a smaller number of cancers, which may reflect a compensatory mechanism to control IGF-II actions or IGF-independent actions. 25808083 3 20 theme apoptosis 363:371 arg1 promotion 350:358 promotion 350:358 promotion of apoptosis in some cells 350:385 IGFBP-6 has recently been shown to have a number of IGF-independent actions, including promotion of apoptosis in some cells and inhibition of angiogenesis. 25808083 3 20 theme apoptosis 363:371 arg1 inhibition 391:400 inhibition 391:400 inhibition of angiogenesis 391:416 IGFBP-6 has recently been shown to have a number of IGF-independent actions, including promotion of apoptosis in some cells and inhibition of angiogenesis. 25808083 7 21 dep cell 780:783 arg1 survival 785:792 survival 785:792 survival 785:792 IGFBP-6 may enter the nucleus and modulate cell survival and differentiation. 25808083 0 22 theme Recent 0:5 arg1 insights 7:14 Recent insights 0:14 Recent insights into the actions of IGFBP-6 0:42 Recent insights into the actions of IGFBP-6. 25808083 10 23 theme IGF-dependent 1118:1130 arg1 actions 1152:1158 IGF-dependent and IGF-independent actions 1118:1158 IGF-dependent and IGF-independent actions of IGFBP-6 1118:1169 The relative balance of IGF-dependent and IGF-independent actions of IGFBP-6 in vivo together with the related question regarding the roles of IGFBP-6 binding to IGF and non-IGF ligands are keys to understanding the physiological role of this protein. 25808083 0 24 theme IGFBP-6 36:42 arg1 actions 25:31 the actions 21:31 the actions of IGFBP-6 21:42 Recent insights into the actions of IGFBP-6. 25808083 3 25 theme angiogenesis 405:416 arg1 promotion 350:358 promotion 350:358 promotion of apoptosis in some cells 350:385 IGFBP-6 has recently been shown to have a number of IGF-independent actions, including promotion of apoptosis in some cells and inhibition of angiogenesis. 25808083 3 25 theme angiogenesis 405:416 arg1 inhibition 391:400 inhibition 391:400 inhibition of angiogenesis 391:416 IGFBP-6 has recently been shown to have a number of IGF-independent actions, including promotion of apoptosis in some cells and inhibition of angiogenesis. 25808083 6 26 theme kinases 728:734 arg1 mechanism 691:699 a mechanism 689:699 a mechanism that is independent of MAP kinases 689:734 IGFBP-6 binds to prohibitin-2 on the cell surface and the latter is required for IGFBP-6-induced migration by a mechanism that is independent of MAP kinases. 25808083 6 26 theme kinases 728:734 arg1 independent 709:719 independent 709:719 independent 709:719 IGFBP-6 binds to prohibitin-2 on the cell surface and the latter is required for IGFBP-6-induced migration by a mechanism that is independent of MAP kinases. 25808083 2 27 theme IGF-II 168:173 arg1 actions 175:181 IGF-II actions 168:181 IGF-II actions 168:181 It is a relatively selective inhibitor of IGF-II actions including proliferation, survival and differentiation of a wide range of cells. 25808083 9 28 theme IGF-independent 1069:1083 arg1 actions 1085:1091 IGF-independent actions 1069:1091 IGF-independent actions 1069:1091 IGFBP-6 expression is increased in a smaller number of cancers, which may reflect a compensatory mechanism to control IGF-II actions or IGF-independent actions. 25808083 9 29 theme smaller 970:976 arg1 number 978:983 a smaller number 968:983 a smaller number 968:983 IGFBP-6 expression is increased in a smaller number of cancers, which may reflect a compensatory mechanism to control IGF-II actions or IGF-independent actions. 25808083 9 30 theme IGF-II 1051:1056 arg1 actions 1058:1064 IGF-II actions 1051:1064 IGF-II actions 1051:1064 IGFBP-6 expression is increased in a smaller number of cancers, which may reflect a compensatory mechanism to control IGF-II actions or IGF-independent actions. 25808083 6 31 theme IGFBP-6-induced 660:674 arg1 migration 676:684 IGFBP-6-induced migration 660:684 IGFBP-6-induced migration 660:684 IGFBP-6 binds to prohibitin-2 on the cell surface and the latter is required for IGFBP-6-induced migration by a mechanism that is independent of MAP kinases. 25808083 10 32 theme actions 1152:1158 arg1 balance 1107:1113 The relative balance 1094:1113 The relative balance of IGF-dependent and IGF-independent actions of IGFBP-6 in vivo together with the related question regarding the roles of IGFBP-6 binding to IGF and non-IGF ligands 1094:1278 The relative balance of IGF-dependent and IGF-independent actions of IGFBP-6 in vivo together with the related question regarding the roles of IGFBP-6 binding to IGF and non-IGF ligands are keys to understanding the physiological role of this protein. 25808083 10 32 theme actions 1152:1158 arg1 keys 1284:1287 keys 1284:1287 keys 1284:1287 The relative balance of IGF-dependent and IGF-independent actions of IGFBP-6 in vivo together with the related question regarding the roles of IGFBP-6 binding to IGF and non-IGF ligands are keys to understanding the physiological role of this protein. 25808083 2 33 theme selective 145:153 arg1 inhibitor 155:163 a relatively selective inhibitor 132:163 a relatively selective inhibitor of IGF-II actions including proliferation, survival and differentiation of a wide range of cells 132:260 It is a relatively selective inhibitor of IGF-II actions including proliferation, survival and differentiation of a wide range of cells. 25808083 2 33 theme selective 145:153 arg1 It 126:127 It 126:127 It 126:127 It is a relatively selective inhibitor of IGF-II actions including proliferation, survival and differentiation of a wide range of cells. 25808083 3 34 from inhibition 391:400 arg1 cells 381:385 some cells 376:385 some cells 376:385 IGFBP-6 has recently been shown to have a number of IGF-independent actions, including promotion of apoptosis in some cells and inhibition of angiogenesis. 25808083 10 35 theme IGF-independent 1136:1150 arg1 actions 1152:1158 IGF-dependent and IGF-independent actions 1118:1158 IGF-dependent and IGF-independent actions of IGFBP-6 1118:1169 The relative balance of IGF-dependent and IGF-independent actions of IGFBP-6 in vivo together with the related question regarding the roles of IGFBP-6 binding to IGF and non-IGF ligands are keys to understanding the physiological role of this protein. 25808083 8 36 theme tumour 914:919 arg1 it 879:880 it 879:880 it 879:880 IGFBP-6 expression is decreased in a number of cancer cells and it has been postulated to act as a tumour suppressor. 25808083 8 36 theme tumour 914:919 arg1 suppressor 921:930 a tumour suppressor 912:930 a tumour suppressor 912:930 IGFBP-6 expression is decreased in a number of cancer cells and it has been postulated to act as a tumour suppressor. 25808083 5 37 theme MAP 566:568 arg1 kinases 570:576 MAP kinases 566:576 MAP kinases 566:576 This chemotactic effect is mediated by MAP kinases. 25808083 6 38 theme MAP 724:726 arg1 kinases 728:734 MAP kinases 724:734 MAP kinases 724:734 IGFBP-6 binds to prohibitin-2 on the cell surface and the latter is required for IGFBP-6-induced migration by a mechanism that is independent of MAP kinases. 25808083 2 39 theme cells 256:260 arg1 range 247:251 a wide range 240:251 a wide range of cells 240:260 It is a relatively selective inhibitor of IGF-II actions including proliferation, survival and differentiation of a wide range of cells. 25808083 2 40 theme range 247:251 arg1 differentiation 221:235 differentiation 221:235 differentiation 221:235 It is a relatively selective inhibitor of IGF-II actions including proliferation, survival and differentiation of a wide range of cells. 25808083 2 40 theme range 247:251 arg1 survival 208:215 survival 208:215 survival 208:215 It is a relatively selective inhibitor of IGF-II actions including proliferation, survival and differentiation of a wide range of cells. 25808083 2 40 theme range 247:251 arg1 proliferation 193:205 proliferation 193:205 proliferation 193:205 It is a relatively selective inhibitor of IGF-II actions including proliferation, survival and differentiation of a wide range of cells. 25808083 10 41 theme physiological 1310:1322 arg1 role 1324:1327 the physiological role 1306:1327 the physiological role of this protein 1306:1343 The relative balance of IGF-dependent and IGF-independent actions of IGFBP-6 in vivo together with the related question regarding the roles of IGFBP-6 binding to IGF and non-IGF ligands are keys to understanding the physiological role of this protein. 25808083 2 42 theme actions 175:181 arg1 inhibitor 155:163 a relatively selective inhibitor 132:163 a relatively selective inhibitor of IGF-II actions including proliferation, survival and differentiation of a wide range of cells 132:260 It is a relatively selective inhibitor of IGF-II actions including proliferation, survival and differentiation of a wide range of cells. 25808083 2 42 theme actions 175:181 arg1 It 126:127 It 126:127 It 126:127 It is a relatively selective inhibitor of IGF-II actions including proliferation, survival and differentiation of a wide range of cells. 25808083 2 43 theme wide 242:245 arg1 range 247:251 a wide range 240:251 a wide range of cells 240:260 It is a relatively selective inhibitor of IGF-II actions including proliferation, survival and differentiation of a wide range of cells. 25808083 3 44 contain have 298:301 arg1 IGFBP-6 263:269 IGFBP-6 263:269 IGFBP-6 263:269 IGFBP-6 has recently been shown to have a number of IGF-independent actions, including promotion of apoptosis in some cells and inhibition of angiogenesis. 25808083 3 44 contain have 298:301 arg2 inhibition 391:400 inhibition 391:400 inhibition of angiogenesis 391:416 IGFBP-6 has recently been shown to have a number of IGF-independent actions, including promotion of apoptosis in some cells and inhibition of angiogenesis. 25808083 3 44 contain have 298:301 arg2 promotion 350:358 promotion 350:358 promotion of apoptosis in some cells 350:385 IGFBP-6 has recently been shown to have a number of IGF-independent actions, including promotion of apoptosis in some cells and inhibition of angiogenesis. 25808083 3 44 contain have 298:301 arg2 number 305:310 a number 303:310 a number of IGF-independent actions, including promotion of apoptosis in some cells and inhibition of angiogenesis 303:416 IGFBP-6 has recently been shown to have a number of IGF-independent actions, including promotion of apoptosis in some cells and inhibition of angiogenesis. 25808083 8 45 theme IGFBP-6 815:821 arg1 expression 823:832 IGFBP-6 expression 815:832 IGFBP-6 expression 815:832 IGFBP-6 expression is decreased in a number of cancer cells and it has been postulated to act as a tumour suppressor. 25808083 10 46 theme IGFBP-6 1163:1169 arg1 actions 1152:1158 IGF-dependent and IGF-independent actions 1118:1158 IGF-dependent and IGF-independent actions of IGFBP-6 1118:1169 The relative balance of IGF-dependent and IGF-independent actions of IGFBP-6 in vivo together with the related question regarding the roles of IGFBP-6 binding to IGF and non-IGF ligands are keys to understanding the physiological role of this protein. 25808083 5 47 theme chemotactic 532:542 arg1 effect 544:549 This chemotactic effect 527:549 This chemotactic effect 527:549 This chemotactic effect is mediated by MAP kinases. 25808083 10 48 theme IGF 1256:1258 arg1 ligands 1272:1278 IGF and non-IGF ligands 1256:1278 IGF and non-IGF ligands 1256:1278 The relative balance of IGF-dependent and IGF-independent actions of IGFBP-6 in vivo together with the related question regarding the roles of IGFBP-6 binding to IGF and non-IGF ligands are keys to understanding the physiological role of this protein. 25808083 1 49 gly glycoprotein 68:79 arg1 IGFBP-6 45:51 IGFBP-6 45:51 IGFBP-6 45:51 IGFBP-6 is an O-linked glycoprotein that preferentially binds IGF-II over IGF-I. 25808083 1 49 gly glycoprotein 68:79 arg1 glycoprotein 68:79 an O-linked glycoprotein 56:79 an O-linked glycoprotein that preferentially binds IGF-II over IGF-I 56:123 IGFBP-6 is an O-linked glycoprotein that preferentially binds IGF-II over IGF-I. 28132190 8 0 theme H. 984:985 arg1 extract 998:1004 H. stipulacea extract 984:1004 H. stipulacea extract 984:1004 H. stipulacea extract contains proteins and polyphenols that could be in charge for the reduction of silver and iron ions into nanoparticles and polysaccharides which stabilized the biosynthesized Ag-NPs and Fe3O4-NPs. 28132190 4 1 theme biosynthesized 614:627 arg1 NPs 629:631 the different biosynthesized NPs 600:631 the different biosynthesized NPs 600:631 The structural composition of the different biosynthesized NPs was studied. 28132190 10 2 theme silver 1586:1591 arg1 profiles 1550:1557 the FTIR profiles 1541:1557 the FTIR profiles of the Ag-NPs and or ionic silver 1541:1591 The study results suggest that the bioactive compounds present in the FTIR profiles of the Ag-NPs and or ionic silver may be the main contributors in their anti-algal effects. 28132190 11 3 theme biosynthesized 1670:1683 arg1 Fe3O4-NPs 1685:1693 the biosynthesized Fe3O4-NPs 1666:1693 the biosynthesized Fe3O4-NPs using H. stipulacea aqueous extract 1666:1729 A trial to use the biosynthesized Fe3O4-NPs using H. stipulacea aqueous extract to separate Ag-NPs was successfully carried out. 28132190 1 4 theme aquatic 276:282 arg1 organisms 284:292 the aquatic organisms 272:292 the aquatic organisms 272:292 This study aims at controlling of the cyanobacteria Oscillatoria simplicissima, those that produce neurotoxins and have negative impacts on the aquatic organisms, using biosynthesized metal nanoparticles (NPs). 28132190 5 5 used used 686:689 arg2 reductants 694:703 reductants 694:703 reductants of AgNO3 694:712 The algae cultures and the extract were used as reductants of AgNO3, and brown colors due to Ag-NP biosynthesis were observed. 28132190 5 5 used used 686:689 arg2 cultures 656:663 The algae cultures 646:663 The algae cultures 646:663 The algae cultures and the extract were used as reductants of AgNO3, and brown colors due to Ag-NP biosynthesis were observed. 28132190 5 5 used used 686:689 arg2 extract 673:679 the extract 669:679 the extract 669:679 The algae cultures and the extract were used as reductants of AgNO3, and brown colors due to Ag-NP biosynthesis were observed. 28132190 10 6 theme main 1604:1607 arg1 contributors 1609:1620 the main contributors 1600:1620 the main contributors in their anti-algal effects 1600:1648 The study results suggest that the bioactive compounds present in the FTIR profiles of the Ag-NPs and or ionic silver may be the main contributors in their anti-algal effects. 28132190 10 6 theme main 1604:1607 arg1 compounds 1520:1528 the bioactive compounds 1506:1528 the bioactive compounds present in the FTIR profiles of the Ag-NPs and or ionic silver 1506:1591 The study results suggest that the bioactive compounds present in the FTIR profiles of the Ag-NPs and or ionic silver may be the main contributors in their anti-algal effects. 28132190 11 7 theme stipulacea 1704:1713 arg1 extract 1723:1729 H. stipulacea aqueous extract 1701:1729 H. stipulacea aqueous extract 1701:1729 A trial to use the biosynthesized Fe3O4-NPs using H. stipulacea aqueous extract to separate Ag-NPs was successfully carried out. 28132190 6 8 theme corresponding 811:823 arg1 spectra 829:835 their corresponding EDX spectra 805:835 their corresponding EDX spectra 805:835 Silver signals were recorded in their corresponding EDX spectra. 28132190 1 9 theme cyanobacteria 170:182 arg1 those 212:216 those 212:216 those 212:216 This study aims at controlling of the cyanobacteria Oscillatoria simplicissima, those that produce neurotoxins and have negative impacts on the aquatic organisms, using biosynthesized metal nanoparticles (NPs). 28132190 1 9 theme cyanobacteria 170:182 arg1 simplicissima 197:209 the cyanobacteria Oscillatoria simplicissima 166:209 the cyanobacteria Oscillatoria simplicissima 166:209 This study aims at controlling of the cyanobacteria Oscillatoria simplicissima, those that produce neurotoxins and have negative impacts on the aquatic organisms, using biosynthesized metal nanoparticles (NPs). 28132190 12 10 theme metal-NPs 1938:1946 arg1 synthesis 1925:1933 the synthesis 1921:1933 the synthesis of metal-NPs 1921:1946 Since the synthesis and applications of nanomaterials is a hot subject of research, the study outcomes not only provide a green approach for the synthesis of metal-NPs but also open the way for more nanoparticle applications. 28132190 10 11 theme anti-algal 1631:1640 arg1 effects 1642:1648 their anti-algal effects 1625:1648 their anti-algal effects 1625:1648 The study results suggest that the bioactive compounds present in the FTIR profiles of the Ag-NPs and or ionic silver may be the main contributors in their anti-algal effects. 28132190 9 12 theme aqueous 1273:1279 arg1 extract 1281:1287 aqueous extract 1273:1287 aqueous extract 1273:1287 The Ag-NPs biosynthesized by T. tetrathele cultures and H. stipulacea aqueous extract exerted outstanding negative impacts on O. simplicissima (optical density and total chlorophyll) and the Ag-NPs biosynthesized using N. oculata culture exerted the moderate performance. 28132190 1 13 contain have 247:250 arg1 those 212:216 those 212:216 those 212:216 This study aims at controlling of the cyanobacteria Oscillatoria simplicissima, those that produce neurotoxins and have negative impacts on the aquatic organisms, using biosynthesized metal nanoparticles (NPs). 28132190 1 13 contain have 247:250 arg1 simplicissima 197:209 the cyanobacteria Oscillatoria simplicissima 166:209 the cyanobacteria Oscillatoria simplicissima 166:209 This study aims at controlling of the cyanobacteria Oscillatoria simplicissima, those that produce neurotoxins and have negative impacts on the aquatic organisms, using biosynthesized metal nanoparticles (NPs). 28132190 1 13 contain have 247:250 arg2 impacts 261:267 negative impacts 252:267 negative impacts on the aquatic organisms 252:292 This study aims at controlling of the cyanobacteria Oscillatoria simplicissima, those that produce neurotoxins and have negative impacts on the aquatic organisms, using biosynthesized metal nanoparticles (NPs). 28132190 5 14 theme AgNO3 708:712 arg1 cultures 656:663 The algae cultures 646:663 The algae cultures 646:663 The algae cultures and the extract were used as reductants of AgNO3, and brown colors due to Ag-NP biosynthesis were observed. 28132190 5 14 theme AgNO3 708:712 arg1 extract 673:679 the extract 669:679 the extract 669:679 The algae cultures and the extract were used as reductants of AgNO3, and brown colors due to Ag-NP biosynthesis were observed. 28132190 5 14 theme AgNO3 708:712 arg1 reductants 694:703 reductants 694:703 reductants of AgNO3 694:712 The algae cultures and the extract were used as reductants of AgNO3, and brown colors due to Ag-NP biosynthesis were observed. 28132190 9 15 theme negative 1309:1316 arg1 impacts 1318:1324 outstanding negative impacts 1297:1324 outstanding negative impacts on O. simplicissima (optical density and total chlorophyll) 1297:1384 The Ag-NPs biosynthesized by T. tetrathele cultures and H. stipulacea aqueous extract exerted outstanding negative impacts on O. simplicissima (optical density and total chlorophyll) and the Ag-NPs biosynthesized using N. oculata culture exerted the moderate performance. 28132190 9 16 dep T. 1232:1233 arg1 cultures 1246:1253 tetrathele cultures 1235:1253 tetrathele cultures 1235:1253 The Ag-NPs biosynthesized by T. tetrathele cultures and H. stipulacea aqueous extract exerted outstanding negative impacts on O. simplicissima (optical density and total chlorophyll) and the Ag-NPs biosynthesized using N. oculata culture exerted the moderate performance. 28132190 2 17 theme tetrathele 447:456 arg1 cultures 458:465 Nannochloropsis oculata and Tetraselmis tetrathele cultures 407:465 cultures 458:465 Silver-NPs (Ag-NPs) have been successfully biosynthesized using Nannochloropsis oculata and Tetraselmis tetrathele cultures. 28132190 9 18 dep H. 1259:1260 arg1 exerted 1289:1295 exerted 1289:1295 exerted outstanding negative impacts on O. simplicissima (optical density and total chlorophyll) 1289:1384 The Ag-NPs biosynthesized by T. tetrathele cultures and H. stipulacea aqueous extract exerted outstanding negative impacts on O. simplicissima (optical density and total chlorophyll) and the Ag-NPs biosynthesized using N. oculata culture exerted the moderate performance. 28132190 9 18 dep H. 1259:1260 arg1 exerted 1441:1447 exerted 1441:1447 exerted the moderate performance 1441:1472 The Ag-NPs biosynthesized by T. tetrathele cultures and H. stipulacea aqueous extract exerted outstanding negative impacts on O. simplicissima (optical density and total chlorophyll) and the Ag-NPs biosynthesized using N. oculata culture exerted the moderate performance. 28132190 9 18 dep H. 1259:1260 arg1 stipulacea 1262:1271 H. stipulacea 1259:1271 H. stipulacea aqueous extract exerted outstanding negative impacts on O. simplicissima (optical density and total chlorophyll) and the Ag-NPs biosynthesized using N. oculata culture exerted the moderate performance 1259:1472 The Ag-NPs biosynthesized by T. tetrathele cultures and H. stipulacea aqueous extract exerted outstanding negative impacts on O. simplicissima (optical density and total chlorophyll) and the Ag-NPs biosynthesized using N. oculata culture exerted the moderate performance. 28132190 10 19 theme bioactive 1510:1518 arg1 contributors 1609:1620 the main contributors 1600:1620 the main contributors in their anti-algal effects 1600:1648 The study results suggest that the bioactive compounds present in the FTIR profiles of the Ag-NPs and or ionic silver may be the main contributors in their anti-algal effects. 28132190 10 19 theme bioactive 1510:1518 arg1 compounds 1520:1528 the bioactive compounds 1506:1528 the bioactive compounds present in the FTIR profiles of the Ag-NPs and or ionic silver 1506:1591 The study results suggest that the bioactive compounds present in the FTIR profiles of the Ag-NPs and or ionic silver may be the main contributors in their anti-algal effects. 28132190 0 20 theme anti-algal 70:79 arg1 efficiencies 81:92 anti-algal efficiencies 70:92 Biosynthesis of metal nanoparticles using three marine plant species: anti-algal efficiencies against "Oscillatoria simplicissima". 0:130 Biosynthesis of metal nanoparticles using three marine plant species: anti-algal efficiencies against "Oscillatoria simplicissima". 28132190 9 21 theme optical 1347:1353 arg1 density 1355:1361 optical density 1347:1361 optical density 1347:1361 The Ag-NPs biosynthesized by T. tetrathele cultures and H. stipulacea aqueous extract exerted outstanding negative impacts on O. simplicissima (optical density and total chlorophyll) and the Ag-NPs biosynthesized using N. oculata culture exerted the moderate performance. 28132190 2 22 theme Nannochloropsis 407:421 arg1 oculata 423:429 Nannochloropsis oculata and Tetraselmis tetrathele cultures 407:465 oculata 423:429 Silver-NPs (Ag-NPs) have been successfully biosynthesized using Nannochloropsis oculata and Tetraselmis tetrathele cultures. 28132190 0 23 theme Oscillatoria 103:114 arg1 " 129:129 "Oscillatoria simplicissima" 102:129 "Oscillatoria simplicissima" 102:129 Biosynthesis of metal nanoparticles using three marine plant species: anti-algal efficiencies against "Oscillatoria simplicissima". 28132190 10 24 theme present 1530:1536 arg1 contributors 1609:1620 the main contributors 1600:1620 the main contributors in their anti-algal effects 1600:1648 The study results suggest that the bioactive compounds present in the FTIR profiles of the Ag-NPs and or ionic silver may be the main contributors in their anti-algal effects. 28132190 10 24 theme present 1530:1536 arg1 compounds 1520:1528 the bioactive compounds 1506:1528 the bioactive compounds present in the FTIR profiles of the Ag-NPs and or ionic silver 1506:1591 The study results suggest that the bioactive compounds present in the FTIR profiles of the Ag-NPs and or ionic silver may be the main contributors in their anti-algal effects. 28132190 8 25 theme silver 1085:1090 arg1 ions 1101:1104 silver and iron ions 1085:1104 silver and iron ions 1085:1104 H. stipulacea extract contains proteins and polyphenols that could be in charge for the reduction of silver and iron ions into nanoparticles and polysaccharides which stabilized the biosynthesized Ag-NPs and Fe3O4-NPs. 28132190 4 26 theme structural 574:583 arg1 composition 585:595 The structural composition 570:595 The structural composition of the different biosynthesized NPs 570:631 The structural composition of the different biosynthesized NPs was studied. 28132190 9 27 theme tetrathele 1235:1244 arg1 cultures 1246:1253 tetrathele cultures 1235:1253 tetrathele cultures 1235:1253 The Ag-NPs biosynthesized by T. tetrathele cultures and H. stipulacea aqueous extract exerted outstanding negative impacts on O. simplicissima (optical density and total chlorophyll) and the Ag-NPs biosynthesized using N. oculata culture exerted the moderate performance. 28132190 3 28 theme iron 485:488 arg1 Fe3O4-NPs 501:509 Fe3O4-NPs 501:509 Fe3O4-NPs 501:509 Also, Ag-NPs and iron oxide-NPs (Fe3O4-NPs) were synthesized by Halophila stipulacea aqueous extract. 28132190 3 28 theme iron 485:488 arg1 oxide-NPs 490:498 iron oxide-NPs 485:498 iron oxide-NPs (Fe3O4-NPs) 485:510 Also, Ag-NPs and iron oxide-NPs (Fe3O4-NPs) were synthesized by Halophila stipulacea aqueous extract. 28132190 0 29 theme metal 16:20 arg1 nanoparticles 22:34 metal nanoparticles 16:34 metal nanoparticles using three marine plant species 16:67 Biosynthesis of metal nanoparticles using three marine plant species: anti-algal efficiencies against "Oscillatoria simplicissima". 28132190 8 30 theme iron 1096:1099 arg1 ions 1101:1104 silver and iron ions 1085:1104 silver and iron ions 1085:1104 H. stipulacea extract contains proteins and polyphenols that could be in charge for the reduction of silver and iron ions into nanoparticles and polysaccharides which stabilized the biosynthesized Ag-NPs and Fe3O4-NPs. 28132190 1 31 theme metal 316:320 arg1 nanoparticles 322:334 biosynthesized metal nanoparticles 301:334 biosynthesized metal nanoparticles (NPs) 301:340 This study aims at controlling of the cyanobacteria Oscillatoria simplicissima, those that produce neurotoxins and have negative impacts on the aquatic organisms, using biosynthesized metal nanoparticles (NPs). 28132190 1 31 theme metal 316:320 arg1 NPs 337:339 NPs 337:339 NPs 337:339 This study aims at controlling of the cyanobacteria Oscillatoria simplicissima, those that produce neurotoxins and have negative impacts on the aquatic organisms, using biosynthesized metal nanoparticles (NPs). 28132190 10 32 theme ionic 1580:1584 arg1 silver 1586:1591 ionic silver 1580:1591 ionic silver 1580:1591 The study results suggest that the bioactive compounds present in the FTIR profiles of the Ag-NPs and or ionic silver may be the main contributors in their anti-algal effects. 28132190 0 33 theme marine 48:53 arg1 species 61:67 three marine plant species 42:67 three marine plant species 42:67 Biosynthesis of metal nanoparticles using three marine plant species: anti-algal efficiencies against "Oscillatoria simplicissima". 28132190 9 34 theme oculata 1425:1431 arg1 culture 1433:1439 N. oculata culture 1422:1439 N. oculata culture 1422:1439 The Ag-NPs biosynthesized by T. tetrathele cultures and H. stipulacea aqueous extract exerted outstanding negative impacts on O. simplicissima (optical density and total chlorophyll) and the Ag-NPs biosynthesized using N. oculata culture exerted the moderate performance. 28132190 10 35 from contributors 1609:1620 arg1 effects 1642:1648 their anti-algal effects 1625:1648 their anti-algal effects 1625:1648 The study results suggest that the bioactive compounds present in the FTIR profiles of the Ag-NPs and or ionic silver may be the main contributors in their anti-algal effects. 28132190 7 36 theme aromatic 933:940 arg1 compounds 942:950 aromatic compounds 933:950 aromatic compounds 933:950 FTIR analyses showed that proteins in N. oculata and T. tetrathele cultures reduced AgNO3, and aromatic compounds stabilized the biogenic Ag-NPs. 28132190 3 37 theme Halophila 532:540 arg1 extract 561:567 Halophila stipulacea aqueous extract 532:567 Halophila stipulacea aqueous extract 532:567 Also, Ag-NPs and iron oxide-NPs (Fe3O4-NPs) were synthesized by Halophila stipulacea aqueous extract. 28132190 9 38 theme moderate 1453:1460 arg1 performance 1462:1472 the moderate performance 1449:1472 the moderate performance 1449:1472 The Ag-NPs biosynthesized by T. tetrathele cultures and H. stipulacea aqueous extract exerted outstanding negative impacts on O. simplicissima (optical density and total chlorophyll) and the Ag-NPs biosynthesized using N. oculata culture exerted the moderate performance. 28132190 0 39 dep Biosynthesis 0:11 arg1 efficiencies 81:92 anti-algal efficiencies 70:92 Biosynthesis of metal nanoparticles using three marine plant species: anti-algal efficiencies against "Oscillatoria simplicissima". 0:130 Biosynthesis of metal nanoparticles using three marine plant species: anti-algal efficiencies against "Oscillatoria simplicissima". 28132190 12 40 theme research 1854:1861 arg1 applications 1804:1815 applications 1804:1815 applications 1804:1815 Since the synthesis and applications of nanomaterials is a hot subject of research, the study outcomes not only provide a green approach for the synthesis of metal-NPs but also open the way for more nanoparticle applications. 28132190 12 40 theme research 1854:1861 arg1 subject 1843:1849 a hot subject 1837:1849 a hot subject of research 1837:1861 Since the synthesis and applications of nanomaterials is a hot subject of research, the study outcomes not only provide a green approach for the synthesis of metal-NPs but also open the way for more nanoparticle applications. 28132190 12 40 theme research 1854:1861 arg1 synthesis 1790:1798 synthesis 1790:1798 synthesis 1790:1798 Since the synthesis and applications of nanomaterials is a hot subject of research, the study outcomes not only provide a green approach for the synthesis of metal-NPs but also open the way for more nanoparticle applications. 28132190 11 41 theme H. 1701:1702 arg1 extract 1723:1729 H. stipulacea aqueous extract 1701:1729 H. stipulacea aqueous extract 1701:1729 A trial to use the biosynthesized Fe3O4-NPs using H. stipulacea aqueous extract to separate Ag-NPs was successfully carried out. 28132190 9 42 from impacts 1318:1324 arg1 simplicissima 1332:1344 O. simplicissima 1329:1344 O. simplicissima (optical density and total chlorophyll) 1329:1384 The Ag-NPs biosynthesized by T. tetrathele cultures and H. stipulacea aqueous extract exerted outstanding negative impacts on O. simplicissima (optical density and total chlorophyll) and the Ag-NPs biosynthesized using N. oculata culture exerted the moderate performance. 28132190 12 43 theme nanomaterials 1820:1832 arg1 applications 1804:1815 applications 1804:1815 applications 1804:1815 Since the synthesis and applications of nanomaterials is a hot subject of research, the study outcomes not only provide a green approach for the synthesis of metal-NPs but also open the way for more nanoparticle applications. 28132190 12 43 theme nanomaterials 1820:1832 arg1 synthesis 1790:1798 synthesis 1790:1798 synthesis 1790:1798 Since the synthesis and applications of nanomaterials is a hot subject of research, the study outcomes not only provide a green approach for the synthesis of metal-NPs but also open the way for more nanoparticle applications. 28132190 12 43 theme nanomaterials 1820:1832 arg1 subject 1843:1849 a hot subject 1837:1849 a hot subject of research 1837:1861 Since the synthesis and applications of nanomaterials is a hot subject of research, the study outcomes not only provide a green approach for the synthesis of metal-NPs but also open the way for more nanoparticle applications. 28132190 4 44 theme different 604:612 arg1 NPs 629:631 the different biosynthesized NPs 600:631 the different biosynthesized NPs 600:631 The structural composition of the different biosynthesized NPs was studied. 28132190 4 45 theme NPs 629:631 arg1 composition 585:595 The structural composition 570:595 The structural composition of the different biosynthesized NPs 570:631 The structural composition of the different biosynthesized NPs was studied. 28132190 6 46 theme EDX 825:827 arg1 spectra 829:835 their corresponding EDX spectra 805:835 their corresponding EDX spectra 805:835 Silver signals were recorded in their corresponding EDX spectra. 28132190 3 47 theme aqueous 553:559 arg1 extract 561:567 Halophila stipulacea aqueous extract 532:567 Halophila stipulacea aqueous extract 532:567 Also, Ag-NPs and iron oxide-NPs (Fe3O4-NPs) were synthesized by Halophila stipulacea aqueous extract. 28132190 11 48 theme aqueous 1715:1721 arg1 extract 1723:1729 H. stipulacea aqueous extract 1701:1729 H. stipulacea aqueous extract 1701:1729 A trial to use the biosynthesized Fe3O4-NPs using H. stipulacea aqueous extract to separate Ag-NPs was successfully carried out. 28132190 10 49 theme study 1479:1483 arg1 results 1485:1491 The study results 1475:1491 The study results 1475:1491 The study results suggest that the bioactive compounds present in the FTIR profiles of the Ag-NPs and or ionic silver may be the main contributors in their anti-algal effects. 28132190 1 50 theme Oscillatoria 184:195 arg1 those 212:216 those 212:216 those 212:216 This study aims at controlling of the cyanobacteria Oscillatoria simplicissima, those that produce neurotoxins and have negative impacts on the aquatic organisms, using biosynthesized metal nanoparticles (NPs). 28132190 1 50 theme Oscillatoria 184:195 arg1 simplicissima 197:209 the cyanobacteria Oscillatoria simplicissima 166:209 the cyanobacteria Oscillatoria simplicissima 166:209 This study aims at controlling of the cyanobacteria Oscillatoria simplicissima, those that produce neurotoxins and have negative impacts on the aquatic organisms, using biosynthesized metal nanoparticles (NPs). 28132190 5 51 theme brown 719:723 arg1 colors 725:730 brown colors 719:730 brown colors due to Ag-NP biosynthesis 719:756 The algae cultures and the extract were used as reductants of AgNO3, and brown colors due to Ag-NP biosynthesis were observed. 28132190 6 52 theme Silver 773:778 arg1 signals 780:786 Silver signals 773:786 Silver signals 773:786 Silver signals were recorded in their corresponding EDX spectra. 28132190 1 53 from impacts 261:267 arg1 organisms 284:292 the aquatic organisms 272:292 the aquatic organisms 272:292 This study aims at controlling of the cyanobacteria Oscillatoria simplicissima, those that produce neurotoxins and have negative impacts on the aquatic organisms, using biosynthesized metal nanoparticles (NPs). 28132190 10 54 from present 1530:1536 arg1 profiles 1550:1557 the FTIR profiles 1541:1557 the FTIR profiles of the Ag-NPs and or ionic silver 1541:1591 The study results suggest that the bioactive compounds present in the FTIR profiles of the Ag-NPs and or ionic silver may be the main contributors in their anti-algal effects. 28132190 9 55 theme outstanding 1297:1307 arg1 impacts 1318:1324 outstanding negative impacts 1297:1324 outstanding negative impacts on O. simplicissima (optical density and total chlorophyll) 1297:1384 The Ag-NPs biosynthesized by T. tetrathele cultures and H. stipulacea aqueous extract exerted outstanding negative impacts on O. simplicissima (optical density and total chlorophyll) and the Ag-NPs biosynthesized using N. oculata culture exerted the moderate performance. 28132190 12 56 theme nanoparticle 1979:1990 arg1 applications 1992:2003 more nanoparticle applications 1974:2003 more nanoparticle applications 1974:2003 Since the synthesis and applications of nanomaterials is a hot subject of research, the study outcomes not only provide a green approach for the synthesis of metal-NPs but also open the way for more nanoparticle applications. 28132190 10 57 from profiles 1550:1557 arg1 present 1530:1536 present 1530:1536 present 1530:1536 The study results suggest that the bioactive compounds present in the FTIR profiles of the Ag-NPs and or ionic silver may be the main contributors in their anti-algal effects. 28132190 12 58 dep synthesis 1790:1798 arg1 the 1786:1788 the 1786:1788 the 1786:1788 Since the synthesis and applications of nanomaterials is a hot subject of research, the study outcomes not only provide a green approach for the synthesis of metal-NPs but also open the way for more nanoparticle applications. 28132190 9 59 theme O. 1329:1330 arg1 simplicissima 1332:1344 O. simplicissima 1329:1344 O. simplicissima (optical density and total chlorophyll) 1329:1384 The Ag-NPs biosynthesized by T. tetrathele cultures and H. stipulacea aqueous extract exerted outstanding negative impacts on O. simplicissima (optical density and total chlorophyll) and the Ag-NPs biosynthesized using N. oculata culture exerted the moderate performance. 28132190 12 60 theme green 1902:1906 arg1 approach 1908:1915 a green approach 1900:1915 a green approach for the synthesis of metal-NPs 1900:1946 Since the synthesis and applications of nanomaterials is a hot subject of research, the study outcomes not only provide a green approach for the synthesis of metal-NPs but also open the way for more nanoparticle applications. 28132190 5 61 theme Ag-NP 739:743 arg1 biosynthesis 745:756 Ag-NP biosynthesis 739:756 Ag-NP biosynthesis 739:756 The algae cultures and the extract were used as reductants of AgNO3, and brown colors due to Ag-NP biosynthesis were observed. 28132190 8 62 contain contains 1006:1013 arg1 extract 998:1004 H. stipulacea extract 984:1004 H. stipulacea extract 984:1004 H. stipulacea extract contains proteins and polyphenols that could be in charge for the reduction of silver and iron ions into nanoparticles and polysaccharides which stabilized the biosynthesized Ag-NPs and Fe3O4-NPs. 28132190 8 62 contain contains 1006:1013 arg2 polyphenols 1028:1038 polyphenols 1028:1038 polyphenols 1028:1038 H. stipulacea extract contains proteins and polyphenols that could be in charge for the reduction of silver and iron ions into nanoparticles and polysaccharides which stabilized the biosynthesized Ag-NPs and Fe3O4-NPs. 28132190 8 62 contain contains 1006:1013 arg2 proteins 1015:1022 proteins 1015:1022 proteins 1015:1022 H. stipulacea extract contains proteins and polyphenols that could be in charge for the reduction of silver and iron ions into nanoparticles and polysaccharides which stabilized the biosynthesized Ag-NPs and Fe3O4-NPs. 28132190 0 63 theme simplicissima 116:128 arg1 " 129:129 "Oscillatoria simplicissima" 102:129 "Oscillatoria simplicissima" 102:129 Biosynthesis of metal nanoparticles using three marine plant species: anti-algal efficiencies against "Oscillatoria simplicissima". 28132190 9 64 theme total 1367:1371 arg1 chlorophyll 1373:1383 total chlorophyll 1367:1383 total chlorophyll 1367:1383 The Ag-NPs biosynthesized by T. tetrathele cultures and H. stipulacea aqueous extract exerted outstanding negative impacts on O. simplicissima (optical density and total chlorophyll) and the Ag-NPs biosynthesized using N. oculata culture exerted the moderate performance. 28132190 5 65 theme algae 650:654 arg1 cultures 656:663 The algae cultures 646:663 The algae cultures 646:663 The algae cultures and the extract were used as reductants of AgNO3, and brown colors due to Ag-NP biosynthesis were observed. 28132190 5 65 theme algae 650:654 arg1 extract 673:679 the extract 669:679 the extract 669:679 The algae cultures and the extract were used as reductants of AgNO3, and brown colors due to Ag-NP biosynthesis were observed. 28132190 5 65 theme algae 650:654 arg1 reductants 694:703 reductants 694:703 reductants of AgNO3 694:712 The algae cultures and the extract were used as reductants of AgNO3, and brown colors due to Ag-NP biosynthesis were observed. 28132190 7 66 theme biogenic 967:974 arg1 Ag-NPs 976:981 the biogenic Ag-NPs 963:981 the biogenic Ag-NPs 963:981 FTIR analyses showed that proteins in N. oculata and T. tetrathele cultures reduced AgNO3, and aromatic compounds stabilized the biogenic Ag-NPs. 28132190 10 67 attach present 1530:1536 arg2 contributors 1609:1620 the main contributors 1600:1620 the main contributors in their anti-algal effects 1600:1648 The study results suggest that the bioactive compounds present in the FTIR profiles of the Ag-NPs and or ionic silver may be the main contributors in their anti-algal effects. 28132190 10 67 attach present 1530:1536 arg2 compounds 1520:1528 the bioactive compounds 1506:1528 the bioactive compounds present in the FTIR profiles of the Ag-NPs and or ionic silver 1506:1591 The study results suggest that the bioactive compounds present in the FTIR profiles of the Ag-NPs and or ionic silver may be the main contributors in their anti-algal effects. 28132190 10 67 attach present 1530:1536 arg1 profiles 1550:1557 the FTIR profiles 1541:1557 the FTIR profiles of the Ag-NPs and or ionic silver 1541:1591 The study results suggest that the bioactive compounds present in the FTIR profiles of the Ag-NPs and or ionic silver may be the main contributors in their anti-algal effects. 28132190 0 68 theme nanoparticles 22:34 arg1 Biosynthesis 0:11 Biosynthesis 0:11 Biosynthesis of metal nanoparticles using three marine plant species: anti-algal efficiencies against "Oscillatoria simplicissima". 0:130 Biosynthesis of metal nanoparticles using three marine plant species: anti-algal efficiencies against "Oscillatoria simplicissima". 28132190 7 69 theme FTIR 838:841 arg1 analyses 843:850 FTIR analyses 838:850 FTIR analyses 838:850 FTIR analyses showed that proteins in N. oculata and T. tetrathele cultures reduced AgNO3, and aromatic compounds stabilized the biogenic Ag-NPs. 28132190 8 70 theme ions 1101:1104 arg1 reduction 1072:1080 the reduction 1068:1080 the reduction of silver and iron ions into nanoparticles and polysaccharides which stabilized the biosynthesized Ag-NPs and Fe3O4-NPs 1068:1200 H. stipulacea extract contains proteins and polyphenols that could be in charge for the reduction of silver and iron ions into nanoparticles and polysaccharides which stabilized the biosynthesized Ag-NPs and Fe3O4-NPs. 28132190 9 71 dep simplicissima 1332:1344 arg1 density 1355:1361 optical density 1347:1361 optical density 1347:1361 The Ag-NPs biosynthesized by T. tetrathele cultures and H. stipulacea aqueous extract exerted outstanding negative impacts on O. simplicissima (optical density and total chlorophyll) and the Ag-NPs biosynthesized using N. oculata culture exerted the moderate performance. 28132190 9 71 dep simplicissima 1332:1344 arg1 chlorophyll 1373:1383 total chlorophyll 1367:1383 total chlorophyll 1367:1383 The Ag-NPs biosynthesized by T. tetrathele cultures and H. stipulacea aqueous extract exerted outstanding negative impacts on O. simplicissima (optical density and total chlorophyll) and the Ag-NPs biosynthesized using N. oculata culture exerted the moderate performance. 28132190 2 72 theme Tetraselmis 435:445 arg1 cultures 458:465 Nannochloropsis oculata and Tetraselmis tetrathele cultures 407:465 cultures 458:465 Silver-NPs (Ag-NPs) have been successfully biosynthesized using Nannochloropsis oculata and Tetraselmis tetrathele cultures. 28132190 1 73 theme biosynthesized 301:314 arg1 nanoparticles 322:334 biosynthesized metal nanoparticles 301:334 biosynthesized metal nanoparticles (NPs) 301:340 This study aims at controlling of the cyanobacteria Oscillatoria simplicissima, those that produce neurotoxins and have negative impacts on the aquatic organisms, using biosynthesized metal nanoparticles (NPs). 28132190 1 73 theme biosynthesized 301:314 arg1 NPs 337:339 NPs 337:339 NPs 337:339 This study aims at controlling of the cyanobacteria Oscillatoria simplicissima, those that produce neurotoxins and have negative impacts on the aquatic organisms, using biosynthesized metal nanoparticles (NPs). 28132190 10 74 theme FTIR 1545:1548 arg1 profiles 1550:1557 the FTIR profiles 1541:1557 the FTIR profiles of the Ag-NPs and or ionic silver 1541:1591 The study results suggest that the bioactive compounds present in the FTIR profiles of the Ag-NPs and or ionic silver may be the main contributors in their anti-algal effects. 28132190 11 75 theme separate 1734:1741 arg1 Ag-NPs 1743:1748 separate Ag-NPs 1734:1748 separate Ag-NPs 1734:1748 A trial to use the biosynthesized Fe3O4-NPs using H. stipulacea aqueous extract to separate Ag-NPs was successfully carried out. 28132190 0 76 theme plant 55:59 arg1 species 61:67 three marine plant species 42:67 three marine plant species 42:67 Biosynthesis of metal nanoparticles using three marine plant species: anti-algal efficiencies against "Oscillatoria simplicissima". 28132190 9 77 theme N. 1422:1423 arg1 culture 1433:1439 N. oculata culture 1422:1439 N. oculata culture 1422:1439 The Ag-NPs biosynthesized by T. tetrathele cultures and H. stipulacea aqueous extract exerted outstanding negative impacts on O. simplicissima (optical density and total chlorophyll) and the Ag-NPs biosynthesized using N. oculata culture exerted the moderate performance. 28132190 7 78 from proteins 864:871 arg1 oculata 879:885 oculata 879:885 oculata 879:885 FTIR analyses showed that proteins in N. oculata and T. tetrathele cultures reduced AgNO3, and aromatic compounds stabilized the biogenic Ag-NPs. 28132190 7 78 from proteins 864:871 arg1 tetrathele 894:903 tetrathele 894:903 tetrathele 894:903 FTIR analyses showed that proteins in N. oculata and T. tetrathele cultures reduced AgNO3, and aromatic compounds stabilized the biogenic Ag-NPs. 28132190 7 79 dep oculata 879:885 arg1 cultures 905:912 cultures 905:912 cultures 905:912 FTIR analyses showed that proteins in N. oculata and T. tetrathele cultures reduced AgNO3, and aromatic compounds stabilized the biogenic Ag-NPs. 28132190 12 80 theme study 1868:1872 arg1 outcomes 1874:1881 the study outcomes 1864:1881 the study outcomes 1864:1881 Since the synthesis and applications of nanomaterials is a hot subject of research, the study outcomes not only provide a green approach for the synthesis of metal-NPs but also open the way for more nanoparticle applications. 28132190 8 81 theme stipulacea 987:996 arg1 extract 998:1004 H. stipulacea extract 984:1004 H. stipulacea extract 984:1004 H. stipulacea extract contains proteins and polyphenols that could be in charge for the reduction of silver and iron ions into nanoparticles and polysaccharides which stabilized the biosynthesized Ag-NPs and Fe3O4-NPs. 28132190 10 82 theme Ag-NPs 1566:1571 arg1 profiles 1550:1557 the FTIR profiles 1541:1557 the FTIR profiles of the Ag-NPs and or ionic silver 1541:1591 The study results suggest that the bioactive compounds present in the FTIR profiles of the Ag-NPs and or ionic silver may be the main contributors in their anti-algal effects. 28132190 8 83 theme biosynthesized 1166:1179 arg1 Ag-NPs 1181:1186 Ag-NPs 1181:1186 Ag-NPs 1181:1186 H. stipulacea extract contains proteins and polyphenols that could be in charge for the reduction of silver and iron ions into nanoparticles and polysaccharides which stabilized the biosynthesized Ag-NPs and Fe3O4-NPs. 28132190 12 84 theme hot 1839:1841 arg1 applications 1804:1815 applications 1804:1815 applications 1804:1815 Since the synthesis and applications of nanomaterials is a hot subject of research, the study outcomes not only provide a green approach for the synthesis of metal-NPs but also open the way for more nanoparticle applications. 28132190 12 84 theme hot 1839:1841 arg1 subject 1843:1849 a hot subject 1837:1849 a hot subject of research 1837:1861 Since the synthesis and applications of nanomaterials is a hot subject of research, the study outcomes not only provide a green approach for the synthesis of metal-NPs but also open the way for more nanoparticle applications. 28132190 12 84 theme hot 1839:1841 arg1 synthesis 1790:1798 synthesis 1790:1798 synthesis 1790:1798 Since the synthesis and applications of nanomaterials is a hot subject of research, the study outcomes not only provide a green approach for the synthesis of metal-NPs but also open the way for more nanoparticle applications. 28132190 3 85 theme stipulacea 542:551 arg1 extract 561:567 Halophila stipulacea aqueous extract 532:567 Halophila stipulacea aqueous extract 532:567 Also, Ag-NPs and iron oxide-NPs (Fe3O4-NPs) were synthesized by Halophila stipulacea aqueous extract. 28132190 1 86 theme negative 252:259 arg1 impacts 261:267 negative impacts 252:267 negative impacts on the aquatic organisms 252:292 This study aims at controlling of the cyanobacteria Oscillatoria simplicissima, those that produce neurotoxins and have negative impacts on the aquatic organisms, using biosynthesized metal nanoparticles (NPs). 26664954 12 0 theme Significant 1418:1428 arg1 P < 0.05 1431:1438 P < 0.05 1431:1438 P < 0.05 1431:1438 Significant (P < 0.05) DFM-associated reductions in supernatant viscosity and C. perfringens proliferation were observed for all non-corn diets. 26664954 12 0 theme Significant 1418:1428 arg1 reductions 1456:1465 Significant (P < 0.05) DFM-associated reductions 1418:1465 Significant (P < 0.05) DFM-associated reductions in supernatant viscosity and C. perfringens proliferation 1418:1523 Significant (P < 0.05) DFM-associated reductions in supernatant viscosity and C. perfringens proliferation were observed for all non-corn diets. 26664954 11 1 theme viable 1346:1351 arg1 spores 1362:1367 viable Bacillus spores 1346:1367 viable Bacillus spores using a plate count method after heat-treatment 1346:1415 Additionally, from each in vitro simulated compartment, samples were taken to enumerate viable Bacillus spores using a plate count method after heat-treatment. 26664954 10 2 theme different 1171:1179 arg1 diets 1181:1185 different diets 1171:1185 different diets 1171:1185 After digestion time, supernatants from different diets were collected to measure viscosity, and C. perfringens proliferation. 26664954 6 3 dep in 519:520 arg1 vitro 522:526 vitro 522:526 vitro 522:526 Furthermore, an in vitro digestive model, simulating different compartments of the gastrointestinal tract, was used to determine the effect of these selected candidates on digesta viscosity and Clostridium perfringens proliferation in different poultry diets. 26664954 11 4 theme count 1383:1387 arg1 method 1389:1394 a plate count method 1375:1394 a plate count method 1375:1394 Additionally, from each in vitro simulated compartment, samples were taken to enumerate viable Bacillus spores using a plate count method after heat-treatment. 26664954 13 5 from cereals 1665:1671 arg1 polysaccharides 1634:1648 non-starch polysaccharides 1623:1648 non-starch polysaccharides from different cereals 1623:1671 These results suggest that antinutritional factors, such as non-starch polysaccharides from different cereals, can enhance viscosity and C. perfringens growth. 26664954 16 6 theme in 2168:2169 arg1 effects 2195:2201 in vivo necrotic enteritis effects 2168:2201 in vivo necrotic enteritis effects 2168:2201 Further studies to evaluate in vivo necrotic enteritis effects are in progress. 26664954 1 7 theme Digestive 178:186 arg1 Model 188:192 an in vitro Digestive Model 166:192 an in vitro Digestive Model in Different Poultry Diets 166:219 for Cellulase and Xylanase Production as Direct-Fed Microbials to Reduce Digesta Viscosity and Clostridium perfringens Proliferation Using an in vitro Digestive Model in Different Poultry Diets. 26664954 4 8 theme study 359:363 arg1 purpose 336:342 The purpose 332:342 The purpose of the present study 332:363 The purpose of the present study was to evaluate the cellulase and xylanase production of these isolates and select the most appropriate Bacillus spp. 26664954 6 9 theme tract 603:607 arg1 compartments 566:577 different compartments 556:577 different compartments of the gastrointestinal tract 556:607 Furthermore, an in vitro digestive model, simulating different compartments of the gastrointestinal tract, was used to determine the effect of these selected candidates on digesta viscosity and Clostridium perfringens proliferation in different poultry diets. 26664954 15 10 theme spores 1932:1937 arg1 % 1919:1919 90% 1917:1919 90% of the DFM spores 1917:1937 Regardless of diet composition, 90% of the DFM spores germinated during the first 30 min in the crop compartment of the digestion model, followed by a noteworthy increased in the intestine compartment by ~2log10, suggesting a full-life cycle development. 26664954 15 10 theme spores 1932:1937 arg1 spores 1932:1937 the DFM spores 1924:1937 the DFM spores 1924:1937 Regardless of diet composition, 90% of the DFM spores germinated during the first 30 min in the crop compartment of the digestion model, followed by a noteworthy increased in the intestine compartment by ~2log10, suggesting a full-life cycle development. 26664954 9 11 from spores/g 1023:1030 arg1 diets 1080:1084 five different sterile soybean-based diets 1043:1084 five different sterile soybean-based diets containing corn, wheat, rye, barley, or oat 1043:1128 The DFM was included at a concentration of 10(8) spores/g of feed in five different sterile soybean-based diets containing corn, wheat, rye, barley, or oat. 26664954 15 12 from 30 min 1967:1972 arg1 compartment 1986:1996 the crop compartment 1977:1996 the crop compartment of the digestion model 1977:2019 Regardless of diet composition, 90% of the DFM spores germinated during the first 30 min in the crop compartment of the digestion model, followed by a noteworthy increased in the intestine compartment by ~2log10, suggesting a full-life cycle development. 26664954 7 13 theme enzyme 829:834 arg1 activity 836:843 their relative enzyme activity 814:843 their relative enzyme activity 814:843 Production of cellulase and xylanase were based on their relative enzyme activity. 26664954 1 14 theme Poultry 207:213 arg1 Diets 215:219 Different Poultry Diets 197:219 Different Poultry Diets 197:219 for Cellulase and Xylanase Production as Direct-Fed Microbials to Reduce Digesta Viscosity and Clostridium perfringens Proliferation Using an in vitro Digestive Model in Different Poultry Diets. 26664954 6 15 from effect 636:641 arg1 proliferation 721:733 Clostridium perfringens proliferation 697:733 Clostridium perfringens proliferation in different poultry diets 697:760 Furthermore, an in vitro digestive model, simulating different compartments of the gastrointestinal tract, was used to determine the effect of these selected candidates on digesta viscosity and Clostridium perfringens proliferation in different poultry diets. 26664954 6 15 from effect 636:641 arg1 viscosity 683:691 digesta viscosity 675:691 digesta viscosity 675:691 Furthermore, an in vitro digestive model, simulating different compartments of the gastrointestinal tract, was used to determine the effect of these selected candidates on digesta viscosity and Clostridium perfringens proliferation in different poultry diets. 26664954 12 16 from reductions 1456:1465 arg1 proliferation 1511:1523 C. perfringens proliferation 1496:1523 C. perfringens proliferation 1496:1523 Significant (P < 0.05) DFM-associated reductions in supernatant viscosity and C. perfringens proliferation were observed for all non-corn diets. 26664954 12 16 from reductions 1456:1465 arg1 viscosity 1482:1490 supernatant viscosity 1470:1490 supernatant viscosity 1470:1490 Significant (P < 0.05) DFM-associated reductions in supernatant viscosity and C. perfringens proliferation were observed for all non-corn diets. 26664954 11 17 theme plate 1377:1381 arg1 method 1389:1394 a plate count method 1375:1394 a plate count method 1375:1394 Additionally, from each in vitro simulated compartment, samples were taken to enumerate viable Bacillus spores using a plate count method after heat-treatment. 26664954 15 18 theme diet 1899:1902 arg1 composition 1904:1914 diet composition 1899:1914 diet composition 1899:1914 Regardless of diet composition, 90% of the DFM spores germinated during the first 30 min in the crop compartment of the digestion model, followed by a noteworthy increased in the intestine compartment by ~2log10, suggesting a full-life cycle development. 26664954 14 19 dep C. 1827:1828 arg1 perfringens 1830:1840 perfringens 1830:1840 perfringens 1830:1840 Remarkably, dietary inclusion of the DFM that produce cellulase and xylanase reduced both viscosity and C. perfringens proliferation compared with control diets. 26664954 15 20 theme model 2015:2019 arg1 compartment 1986:1996 the crop compartment 1977:1996 the crop compartment of the digestion model 1977:2019 Regardless of diet composition, 90% of the DFM spores germinated during the first 30 min in the crop compartment of the digestion model, followed by a noteworthy increased in the intestine compartment by ~2log10, suggesting a full-life cycle development. 26664954 1 21 from Model 188:192 arg1 Diets 215:219 Different Poultry Diets 197:219 Different Poultry Diets 197:219 for Cellulase and Xylanase Production as Direct-Fed Microbials to Reduce Digesta Viscosity and Clostridium perfringens Proliferation Using an in vitro Digestive Model in Different Poultry Diets. 26664954 14 22 theme control 1870:1876 arg1 diets 1878:1882 control diets 1870:1882 control diets 1870:1882 Remarkably, dietary inclusion of the DFM that produce cellulase and xylanase reduced both viscosity and C. perfringens proliferation compared with control diets. 26664954 9 23 theme spores/g 1023:1030 arg1 concentration 1000:1012 a concentration 998:1012 a concentration of 10(8) spores/g of feed in five different sterile soybean-based diets containing corn, wheat, rye, barley, or oat 998:1128 The DFM was included at a concentration of 10(8) spores/g of feed in five different sterile soybean-based diets containing corn, wheat, rye, barley, or oat. 26664954 8 24 theme 16S 858:860 arg1 rRNA 862:865 16S rRNA 858:865 16S rRNA sequence 858:874 Analysis of 16S rRNA sequence classified two strains as Bacillus amyloliquefaciens and one of the strains as Bacillus subtilis. 26664954 9 25 theme feed 1035:1038 arg1 spores/g 1023:1030 10(8) spores/g 1017:1030 10(8) spores/g of feed in five different sterile soybean-based diets containing corn, wheat, rye, barley, or oat 1017:1128 The DFM was included at a concentration of 10(8) spores/g of feed in five different sterile soybean-based diets containing corn, wheat, rye, barley, or oat. 26664954 1 26 theme in 169:170 arg1 Model 188:192 an in vitro Digestive Model 166:192 an in vitro Digestive Model in Different Poultry Diets 166:219 for Cellulase and Xylanase Production as Direct-Fed Microbials to Reduce Digesta Viscosity and Clostridium perfringens Proliferation Using an in vitro Digestive Model in Different Poultry Diets. 26664954 8 27 theme sequence 867:874 arg1 Analysis 846:853 Analysis 846:853 Analysis of 16S rRNA sequence 846:874 Analysis of 16S rRNA sequence classified two strains as Bacillus amyloliquefaciens and one of the strains as Bacillus subtilis. 26664954 9 28 from concentration 1000:1012 arg1 diets 1080:1084 five different sterile soybean-based diets 1043:1084 five different sterile soybean-based diets containing corn, wheat, rye, barley, or oat 1043:1128 The DFM was included at a concentration of 10(8) spores/g of feed in five different sterile soybean-based diets containing corn, wheat, rye, barley, or oat. 26664954 1 29 dep Clostridium 122:132 arg1 perfringens 134:144 perfringens 134:144 perfringens 134:144 for Cellulase and Xylanase Production as Direct-Fed Microbials to Reduce Digesta Viscosity and Clostridium perfringens Proliferation Using an in vitro Digestive Model in Different Poultry Diets. 26664954 10 30 dep C. 1228:1229 arg1 perfringens 1231:1241 perfringens 1231:1241 perfringens 1231:1241 After digestion time, supernatants from different diets were collected to measure viscosity, and C. perfringens proliferation. 26664954 15 31 theme intestine 2064:2072 arg1 compartment 2074:2084 the intestine compartment 2060:2084 the intestine compartment 2060:2084 Regardless of diet composition, 90% of the DFM spores germinated during the first 30 min in the crop compartment of the digestion model, followed by a noteworthy increased in the intestine compartment by ~2log10, suggesting a full-life cycle development. 26664954 4 32 theme appropriate 457:467 arg1 spp 478:480 the most appropriate Bacillus spp 448:480 the most appropriate Bacillus spp 448:480 The purpose of the present study was to evaluate the cellulase and xylanase production of these isolates and select the most appropriate Bacillus spp. 26664954 6 33 theme Clostridium 697:707 arg1 proliferation 721:733 Clostridium perfringens proliferation 697:733 Clostridium perfringens proliferation in different poultry diets 697:760 Furthermore, an in vitro digestive model, simulating different compartments of the gastrointestinal tract, was used to determine the effect of these selected candidates on digesta viscosity and Clostridium perfringens proliferation in different poultry diets. 26664954 1 34 theme Direct-Fed 68:77 arg1 Microbials 79:88 Direct-Fed Microbials 68:88 Direct-Fed Microbials 68:88 for Cellulase and Xylanase Production as Direct-Fed Microbials to Reduce Digesta Viscosity and Clostridium perfringens Proliferation Using an in vitro Digestive Model in Different Poultry Diets. 26664954 15 35 theme DFM 1928:1930 arg1 spores 1932:1937 the DFM spores 1924:1937 the DFM spores 1924:1937 Regardless of diet composition, 90% of the DFM spores germinated during the first 30 min in the crop compartment of the digestion model, followed by a noteworthy increased in the intestine compartment by ~2log10, suggesting a full-life cycle development. 26664954 16 36 dep in 2168:2169 arg1 vivo 2171:2174 vivo 2171:2174 vivo 2171:2174 Further studies to evaluate in vivo necrotic enteritis effects are in progress. 26664954 14 37 theme C. 1827:1828 arg1 proliferation 1842:1854 C. perfringens proliferation 1827:1854 C. perfringens proliferation 1827:1854 Remarkably, dietary inclusion of the DFM that produce cellulase and xylanase reduced both viscosity and C. perfringens proliferation compared with control diets. 26664954 13 38 theme different 1655:1663 arg1 cereals 1665:1671 different cereals 1655:1671 different cereals 1655:1671 These results suggest that antinutritional factors, such as non-starch polysaccharides from different cereals, can enhance viscosity and C. perfringens growth. 26664954 6 39 dep Clostridium 697:707 arg1 perfringens 709:719 perfringens 709:719 perfringens 709:719 Furthermore, an in vitro digestive model, simulating different compartments of the gastrointestinal tract, was used to determine the effect of these selected candidates on digesta viscosity and Clostridium perfringens proliferation in different poultry diets. 26664954 0 40 theme Bacillus 13:20 arg1 Selection 0:8 Selection 0:8 Selection of Bacillus 0:20 Selection of Bacillus spp. 26664954 1 41 theme Digesta 100:106 arg1 Viscosity 108:116 Digesta Viscosity 100:116 Digesta Viscosity 100:116 for Cellulase and Xylanase Production as Direct-Fed Microbials to Reduce Digesta Viscosity and Clostridium perfringens Proliferation Using an in vitro Digestive Model in Different Poultry Diets. 26664954 6 42 theme selected 652:659 arg1 candidates 661:670 these selected candidates 646:670 these selected candidates 646:670 Furthermore, an in vitro digestive model, simulating different compartments of the gastrointestinal tract, was used to determine the effect of these selected candidates on digesta viscosity and Clostridium perfringens proliferation in different poultry diets. 26664954 7 43 theme xylanase 791:798 arg1 Production 763:772 Production 763:772 Production of cellulase and xylanase 763:798 Production of cellulase and xylanase were based on their relative enzyme activity. 26664954 15 44 theme cycle 2121:2125 arg1 development 2127:2137 a full-life cycle development 2109:2137 a full-life cycle development 2109:2137 Regardless of diet composition, 90% of the DFM spores germinated during the first 30 min in the crop compartment of the digestion model, followed by a noteworthy increased in the intestine compartment by ~2log10, suggesting a full-life cycle development. 26664954 7 45 theme cellulase 777:785 arg1 Production 763:772 Production 763:772 Production of cellulase and xylanase 763:798 Production of cellulase and xylanase were based on their relative enzyme activity. 26664954 4 46 theme present 351:357 arg1 study 359:363 the present study 347:363 the present study 347:363 The purpose of the present study was to evaluate the cellulase and xylanase production of these isolates and select the most appropriate Bacillus spp. 26664954 6 47 used used 614:617 arg2 model 538:542 an in vitro digestive model 516:542 an in vitro digestive model 516:542 Furthermore, an in vitro digestive model, simulating different compartments of the gastrointestinal tract, was used to determine the effect of these selected candidates on digesta viscosity and Clostridium perfringens proliferation in different poultry diets. 26664954 12 48 theme supernatant 1470:1480 arg1 viscosity 1482:1490 supernatant viscosity 1470:1490 supernatant viscosity 1470:1490 Significant (P < 0.05) DFM-associated reductions in supernatant viscosity and C. perfringens proliferation were observed for all non-corn diets. 26664954 11 49 theme Bacillus 1353:1360 arg1 spores 1362:1367 viable Bacillus spores 1346:1367 viable Bacillus spores using a plate count method after heat-treatment 1346:1415 Additionally, from each in vitro simulated compartment, samples were taken to enumerate viable Bacillus spores using a plate count method after heat-treatment. 26664954 6 50 theme different 738:746 arg1 diets 756:760 different poultry diets 738:760 different poultry diets 738:760 Furthermore, an in vitro digestive model, simulating different compartments of the gastrointestinal tract, was used to determine the effect of these selected candidates on digesta viscosity and Clostridium perfringens proliferation in different poultry diets. 26664954 14 51 theme DFM 1760:1762 arg1 inclusion 1743:1751 dietary inclusion 1735:1751 dietary inclusion of the DFM that produce cellulase and xylanase 1735:1798 Remarkably, dietary inclusion of the DFM that produce cellulase and xylanase reduced both viscosity and C. perfringens proliferation compared with control diets. 26664954 6 52 from proliferation 721:733 arg1 diets 756:760 different poultry diets 738:760 different poultry diets 738:760 Furthermore, an in vitro digestive model, simulating different compartments of the gastrointestinal tract, was used to determine the effect of these selected candidates on digesta viscosity and Clostridium perfringens proliferation in different poultry diets. 26664954 6 53 theme digestive 528:536 arg1 model 538:542 an in vitro digestive model 516:542 an in vitro digestive model 516:542 Furthermore, an in vitro digestive model, simulating different compartments of the gastrointestinal tract, was used to determine the effect of these selected candidates on digesta viscosity and Clostridium perfringens proliferation in different poultry diets. 26664954 6 54 theme in 519:520 arg1 model 538:542 an in vitro digestive model 516:542 an in vitro digestive model 516:542 Furthermore, an in vitro digestive model, simulating different compartments of the gastrointestinal tract, was used to determine the effect of these selected candidates on digesta viscosity and Clostridium perfringens proliferation in different poultry diets. 26664954 13 55 theme antinutritional 1590:1604 arg1 polysaccharides 1634:1648 non-starch polysaccharides 1623:1648 non-starch polysaccharides from different cereals 1623:1671 These results suggest that antinutritional factors, such as non-starch polysaccharides from different cereals, can enhance viscosity and C. perfringens growth. 26664954 13 55 theme antinutritional 1590:1604 arg1 factors 1606:1612 antinutritional factors 1590:1612 antinutritional factors 1590:1612 These results suggest that antinutritional factors, such as non-starch polysaccharides from different cereals, can enhance viscosity and C. perfringens growth. 26664954 14 56 theme dietary 1735:1741 arg1 inclusion 1743:1751 dietary inclusion 1735:1751 dietary inclusion of the DFM that produce cellulase and xylanase 1735:1798 Remarkably, dietary inclusion of the DFM that produce cellulase and xylanase reduced both viscosity and C. perfringens proliferation compared with control diets. 26664954 4 57 theme xylanase 399:406 arg1 production 408:417 xylanase production 399:417 xylanase production 399:417 The purpose of the present study was to evaluate the cellulase and xylanase production of these isolates and select the most appropriate Bacillus spp. 26664954 6 58 from viscosity 683:691 arg1 diets 756:760 different poultry diets 738:760 different poultry diets 738:760 Furthermore, an in vitro digestive model, simulating different compartments of the gastrointestinal tract, was used to determine the effect of these selected candidates on digesta viscosity and Clostridium perfringens proliferation in different poultry diets. 26664954 6 59 theme gastrointestinal 586:601 arg1 tract 603:607 the gastrointestinal tract 582:607 the gastrointestinal tract 582:607 Furthermore, an in vitro digestive model, simulating different compartments of the gastrointestinal tract, was used to determine the effect of these selected candidates on digesta viscosity and Clostridium perfringens proliferation in different poultry diets. 26664954 16 60 theme Further 2140:2146 arg1 studies 2148:2154 Further studies 2140:2154 Further studies to evaluate in vivo necrotic enteritis effects 2140:2201 Further studies to evaluate in vivo necrotic enteritis effects are in progress. 26664954 1 61 theme Different 197:205 arg1 Diets 215:219 Different Poultry Diets 197:219 Different Poultry Diets 197:219 for Cellulase and Xylanase Production as Direct-Fed Microbials to Reduce Digesta Viscosity and Clostridium perfringens Proliferation Using an in vitro Digestive Model in Different Poultry Diets. 26664954 13 62 dep C. 1700:1701 arg1 perfringens 1703:1713 perfringens 1703:1713 perfringens 1703:1713 These results suggest that antinutritional factors, such as non-starch polysaccharides from different cereals, can enhance viscosity and C. perfringens growth. 26664954 6 63 theme different 556:564 arg1 compartments 566:577 different compartments 556:577 different compartments of the gastrointestinal tract 556:607 Furthermore, an in vitro digestive model, simulating different compartments of the gastrointestinal tract, was used to determine the effect of these selected candidates on digesta viscosity and Clostridium perfringens proliferation in different poultry diets. 26664954 10 64 from diets 1181:1185 arg1 supernatants 1153:1164 supernatants 1153:1164 supernatants from different diets 1153:1185 After digestion time, supernatants from different diets were collected to measure viscosity, and C. perfringens proliferation. 26664954 1 65 theme Clostridium 122:132 arg1 Proliferation 146:158 Clostridium perfringens Proliferation 122:158 Clostridium perfringens Proliferation 122:158 for Cellulase and Xylanase Production as Direct-Fed Microbials to Reduce Digesta Viscosity and Clostridium perfringens Proliferation Using an in vitro Digestive Model in Different Poultry Diets. 26664954 12 66 theme non-corn 1547:1554 arg1 diets 1556:1560 all non-corn diets 1543:1560 all non-corn diets 1543:1560 Significant (P < 0.05) DFM-associated reductions in supernatant viscosity and C. perfringens proliferation were observed for all non-corn diets. 26664954 3 67 theme direct-fed 303:312 arg1 DFM 326:328 DFM 326:328 DFM 326:328 isolates as direct-fed microbials (DFM). 26664954 3 67 theme direct-fed 303:312 arg1 microbials 314:323 direct-fed microbials 303:323 direct-fed microbials (DFM) 303:329 isolates as direct-fed microbials (DFM). 26664954 4 68 theme isolates 428:435 arg1 cellulase 385:393 cellulase 385:393 cellulase 385:393 The purpose of the present study was to evaluate the cellulase and xylanase production of these isolates and select the most appropriate Bacillus spp. 26664954 4 68 theme isolates 428:435 arg1 production 408:417 xylanase production 399:417 xylanase production 399:417 The purpose of the present study was to evaluate the cellulase and xylanase production of these isolates and select the most appropriate Bacillus spp. 26664954 11 69 theme simulated 1291:1299 arg1 compartment 1301:1311 each in vitro simulated compartment 1277:1311 each in vitro simulated compartment 1277:1311 Additionally, from each in vitro simulated compartment, samples were taken to enumerate viable Bacillus spores using a plate count method after heat-treatment. 26664954 10 70 theme C. 1228:1229 arg1 proliferation 1243:1255 C. perfringens proliferation 1228:1255 C. perfringens proliferation 1228:1255 After digestion time, supernatants from different diets were collected to measure viscosity, and C. perfringens proliferation. 26664954 4 71 dep cellulase 385:393 arg1 the 381:383 the 381:383 the 381:383 The purpose of the present study was to evaluate the cellulase and xylanase production of these isolates and select the most appropriate Bacillus spp. 26664954 12 72 dep C. 1496:1497 arg1 perfringens 1499:1509 perfringens 1499:1509 perfringens 1499:1509 Significant (P < 0.05) DFM-associated reductions in supernatant viscosity and C. perfringens proliferation were observed for all non-corn diets. 26664954 1 73 theme Xylanase 45:52 arg1 Production 54:63 Xylanase Production 45:63 Xylanase Production 45:63 for Cellulase and Xylanase Production as Direct-Fed Microbials to Reduce Digesta Viscosity and Clostridium perfringens Proliferation Using an in vitro Digestive Model in Different Poultry Diets. 26664954 8 74 theme rRNA 862:865 arg1 sequence 867:874 16S rRNA sequence 858:874 16S rRNA sequence 858:874 Analysis of 16S rRNA sequence classified two strains as Bacillus amyloliquefaciens and one of the strains as Bacillus subtilis. 26664954 4 75 theme Bacillus 469:476 arg1 spp 478:480 the most appropriate Bacillus spp 448:480 the most appropriate Bacillus spp 448:480 The purpose of the present study was to evaluate the cellulase and xylanase production of these isolates and select the most appropriate Bacillus spp. 26664954 15 76 theme first 1961:1965 arg1 30 min 1967:1972 the first 30 min 1957:1972 the first 30 min in the crop compartment of the digestion model 1957:2019 Regardless of diet composition, 90% of the DFM spores germinated during the first 30 min in the crop compartment of the digestion model, followed by a noteworthy increased in the intestine compartment by ~2log10, suggesting a full-life cycle development. 26664954 9 77 theme different 1048:1056 arg1 diets 1080:1084 five different sterile soybean-based diets 1043:1084 five different sterile soybean-based diets containing corn, wheat, rye, barley, or oat 1043:1128 The DFM was included at a concentration of 10(8) spores/g of feed in five different sterile soybean-based diets containing corn, wheat, rye, barley, or oat. 26664954 11 78 theme in 1282:1283 arg1 compartment 1301:1311 each in vitro simulated compartment 1277:1311 each in vitro simulated compartment 1277:1311 Additionally, from each in vitro simulated compartment, samples were taken to enumerate viable Bacillus spores using a plate count method after heat-treatment. 26664954 9 79 theme soybean-based 1066:1078 arg1 diets 1080:1084 five different sterile soybean-based diets 1043:1084 five different sterile soybean-based diets containing corn, wheat, rye, barley, or oat 1043:1128 The DFM was included at a concentration of 10(8) spores/g of feed in five different sterile soybean-based diets containing corn, wheat, rye, barley, or oat. 26664954 9 80 contain containing 1086:1095 arg2 rye 1110:1112 rye 1110:1112 rye 1110:1112 The DFM was included at a concentration of 10(8) spores/g of feed in five different sterile soybean-based diets containing corn, wheat, rye, barley, or oat. 26664954 9 80 contain containing 1086:1095 arg2 corn 1097:1100 corn 1097:1100 corn 1097:1100 The DFM was included at a concentration of 10(8) spores/g of feed in five different sterile soybean-based diets containing corn, wheat, rye, barley, or oat. 26664954 9 80 contain containing 1086:1095 arg2 barley 1115:1120 barley 1115:1120 barley 1115:1120 The DFM was included at a concentration of 10(8) spores/g of feed in five different sterile soybean-based diets containing corn, wheat, rye, barley, or oat. 26664954 9 80 contain containing 1086:1095 arg2 wheat 1103:1107 wheat 1103:1107 wheat 1103:1107 The DFM was included at a concentration of 10(8) spores/g of feed in five different sterile soybean-based diets containing corn, wheat, rye, barley, or oat. 26664954 9 80 contain containing 1086:1095 arg1 diets 1080:1084 five different sterile soybean-based diets 1043:1084 five different sterile soybean-based diets containing corn, wheat, rye, barley, or oat 1043:1128 The DFM was included at a concentration of 10(8) spores/g of feed in five different sterile soybean-based diets containing corn, wheat, rye, barley, or oat. 26664954 9 80 contain containing 1086:1095 arg2 oat 1126:1128 oat 1126:1128 oat 1126:1128 The DFM was included at a concentration of 10(8) spores/g of feed in five different sterile soybean-based diets containing corn, wheat, rye, barley, or oat. 26664954 16 81 theme enteritis 2185:2193 arg1 effects 2195:2201 in vivo necrotic enteritis effects 2168:2201 in vivo necrotic enteritis effects 2168:2201 Further studies to evaluate in vivo necrotic enteritis effects are in progress. 26664954 13 82 theme C. 1700:1701 arg1 growth 1715:1720 C. perfringens growth 1700:1720 C. perfringens growth 1700:1720 These results suggest that antinutritional factors, such as non-starch polysaccharides from different cereals, can enhance viscosity and C. perfringens growth. 26664954 1 83 dep in 169:170 arg1 vitro 172:176 vitro 172:176 vitro 172:176 for Cellulase and Xylanase Production as Direct-Fed Microbials to Reduce Digesta Viscosity and Clostridium perfringens Proliferation Using an in vitro Digestive Model in Different Poultry Diets. 26664954 6 84 theme digesta 675:681 arg1 viscosity 683:691 digesta viscosity 675:691 digesta viscosity 675:691 Furthermore, an in vitro digestive model, simulating different compartments of the gastrointestinal tract, was used to determine the effect of these selected candidates on digesta viscosity and Clostridium perfringens proliferation in different poultry diets. 26664954 7 85 theme relative 820:827 arg1 activity 836:843 their relative enzyme activity 814:843 their relative enzyme activity 814:843 Production of cellulase and xylanase were based on their relative enzyme activity. 26664954 6 86 theme candidates 661:670 arg1 effect 636:641 the effect 632:641 the effect of these selected candidates on digesta viscosity and Clostridium perfringens proliferation in different poultry diets 632:760 Furthermore, an in vitro digestive model, simulating different compartments of the gastrointestinal tract, was used to determine the effect of these selected candidates on digesta viscosity and Clostridium perfringens proliferation in different poultry diets. 26664954 16 87 dep studies 2148:2154 arg1 evaluate 2159:2166 evaluate 2159:2166 to evaluate in vivo necrotic enteritis effects 2156:2201 Further studies to evaluate in vivo necrotic enteritis effects are in progress. 26664954 9 88 theme sterile 1058:1064 arg1 diets 1080:1084 five different sterile soybean-based diets 1043:1084 five different sterile soybean-based diets containing corn, wheat, rye, barley, or oat 1043:1128 The DFM was included at a concentration of 10(8) spores/g of feed in five different sterile soybean-based diets containing corn, wheat, rye, barley, or oat. 26664954 15 89 theme full-life 2111:2119 arg1 development 2127:2137 a full-life cycle development 2109:2137 a full-life cycle development 2109:2137 Regardless of diet composition, 90% of the DFM spores germinated during the first 30 min in the crop compartment of the digestion model, followed by a noteworthy increased in the intestine compartment by ~2log10, suggesting a full-life cycle development. 26664954 15 90 theme digestion 2005:2013 arg1 model 2015:2019 the digestion model 2001:2019 the digestion model 2001:2019 Regardless of diet composition, 90% of the DFM spores germinated during the first 30 min in the crop compartment of the digestion model, followed by a noteworthy increased in the intestine compartment by ~2log10, suggesting a full-life cycle development. 26664954 10 91 theme digestion 1137:1145 arg1 time 1147:1150 digestion time 1137:1150 digestion time 1137:1150 After digestion time, supernatants from different diets were collected to measure viscosity, and C. perfringens proliferation. 26664954 15 92 dep germinated 1939:1948 arg1 followed 2022:2029 followed 2022:2029 followed 2022:2029 Regardless of diet composition, 90% of the DFM spores germinated during the first 30 min in the crop compartment of the digestion model, followed by a noteworthy increased in the intestine compartment by ~2log10, suggesting a full-life cycle development. 26664954 12 93 theme C. 1496:1497 arg1 proliferation 1511:1523 C. perfringens proliferation 1496:1523 C. perfringens proliferation 1496:1523 Significant (P < 0.05) DFM-associated reductions in supernatant viscosity and C. perfringens proliferation were observed for all non-corn diets. 26664954 11 94 dep in 1282:1283 arg1 vitro 1285:1289 vitro 1285:1289 vitro 1285:1289 Additionally, from each in vitro simulated compartment, samples were taken to enumerate viable Bacillus spores using a plate count method after heat-treatment. 26664954 13 95 theme non-starch 1623:1632 arg1 polysaccharides 1634:1648 non-starch polysaccharides 1623:1648 non-starch polysaccharides from different cereals 1623:1671 These results suggest that antinutritional factors, such as non-starch polysaccharides from different cereals, can enhance viscosity and C. perfringens growth. 26664954 12 96 theme DFM-associated 1441:1454 arg1 P < 0.05 1431:1438 P < 0.05 1431:1438 P < 0.05 1431:1438 Significant (P < 0.05) DFM-associated reductions in supernatant viscosity and C. perfringens proliferation were observed for all non-corn diets. 26664954 12 96 theme DFM-associated 1441:1454 arg1 reductions 1456:1465 Significant (P < 0.05) DFM-associated reductions 1418:1465 Significant (P < 0.05) DFM-associated reductions in supernatant viscosity and C. perfringens proliferation 1418:1523 Significant (P < 0.05) DFM-associated reductions in supernatant viscosity and C. perfringens proliferation were observed for all non-corn diets. 26664954 8 97 theme strains 944:950 arg1 strains 944:950 the strains 940:950 the strains 940:950 Analysis of 16S rRNA sequence classified two strains as Bacillus amyloliquefaciens and one of the strains as Bacillus subtilis. 26664954 8 97 theme strains 944:950 arg1 one 933:935 one 933:935 one 933:935 Analysis of 16S rRNA sequence classified two strains as Bacillus amyloliquefaciens and one of the strains as Bacillus subtilis. 26664954 15 98 theme crop 1981:1984 arg1 compartment 1986:1996 the crop compartment 1977:1996 the crop compartment of the digestion model 1977:2019 Regardless of diet composition, 90% of the DFM spores germinated during the first 30 min in the crop compartment of the digestion model, followed by a noteworthy increased in the intestine compartment by ~2log10, suggesting a full-life cycle development. 26664954 9 99 from diets 1080:1084 arg1 concentration 1000:1012 a concentration 998:1012 a concentration of 10(8) spores/g of feed in five different sterile soybean-based diets containing corn, wheat, rye, barley, or oat 998:1128 The DFM was included at a concentration of 10(8) spores/g of feed in five different sterile soybean-based diets containing corn, wheat, rye, barley, or oat. 26664954 6 100 theme poultry 748:754 arg1 diets 756:760 different poultry diets 738:760 different poultry diets 738:760 Furthermore, an in vitro digestive model, simulating different compartments of the gastrointestinal tract, was used to determine the effect of these selected candidates on digesta viscosity and Clostridium perfringens proliferation in different poultry diets. 26664954 16 101 theme necrotic 2176:2183 arg1 effects 2195:2201 in vivo necrotic enteritis effects 2168:2201 in vivo necrotic enteritis effects 2168:2201 Further studies to evaluate in vivo necrotic enteritis effects are in progress. 27658790 0 0 theme modulators 79:88 arg1 synthesis 8:16 synthesis 8:16 synthesis 8:16 Design, synthesis, and biological characterization of novel PEG-linked dimeric modulators for CXCR4. 27658790 0 0 theme modulators 79:88 arg1 Design 0:5 Design 0:5 Design 0:5 Design, synthesis, and biological characterization of novel PEG-linked dimeric modulators for CXCR4. 27658790 0 0 theme modulators 79:88 arg1 characterization 34:49 biological characterization 23:49 biological characterization 23:49 Design, synthesis, and biological characterization of novel PEG-linked dimeric modulators for CXCR4. 27658790 6 1 theme CXCR4 1270:1274 arg1 IC50=407nM 1285:1294 IC50=407nM 1285:1294 IC50=407nM 1285:1294 Chemotaxis and calcium mobilization assays with SUP-T1 cells further identified two promising lead modulators of CXCR4: ligand 4, a [PEG3]2 linked homodimeric DV3, was an effective CXCR4 antagonist (IC50=22nM); and ligand 21, a [PEG3]2 linked heterodimeric DV3-CXCL121-8, was an effective CXCR4 agonist (IC50=407nM). 27658790 6 1 theme CXCR4 1270:1274 arg1 agonist 1276:1282 an effective CXCR4 agonist 1257:1282 an effective CXCR4 agonist (IC50=407nM) 1257:1295 Chemotaxis and calcium mobilization assays with SUP-T1 cells further identified two promising lead modulators of CXCR4: ligand 4, a [PEG3]2 linked homodimeric DV3, was an effective CXCR4 antagonist (IC50=22nM); and ligand 21, a [PEG3]2 linked heterodimeric DV3-CXCL121-8, was an effective CXCR4 agonist (IC50=407nM). 27658790 6 1 theme CXCR4 1270:1274 arg1 ligand 1196:1201 ligand 21 1196:1204 ligand 21 1196:1204 Chemotaxis and calcium mobilization assays with SUP-T1 cells further identified two promising lead modulators of CXCR4: ligand 4, a [PEG3]2 linked homodimeric DV3, was an effective CXCR4 antagonist (IC50=22nM); and ligand 21, a [PEG3]2 linked heterodimeric DV3-CXCL121-8, was an effective CXCR4 agonist (IC50=407nM). 27658790 5 2 theme IC50 934:937 arg1 values 939:944 IC50 values 934:944 IC50 values 934:944 Among a total of 24 peptide ligands, four antagonists and three agonists showed good CXCR4 binding affinity, with IC50 values of <50nM and <800nM, respectively. 27658790 5 3 theme ligands 848:854 arg1 total 828:832 a total 826:832 a total of 24 peptide ligands 826:854 Among a total of 24 peptide ligands, four antagonists and three agonists showed good CXCR4 binding affinity, with IC50 values of <50nM and <800nM, respectively. 27658790 0 4 theme dimeric 71:77 arg1 modulators 79:88 novel PEG-linked dimeric modulators 54:88 novel PEG-linked dimeric modulators for CXCR4 54:98 Design, synthesis, and biological characterization of novel PEG-linked dimeric modulators for CXCR4. 27658790 7 5 theme CXCL12-CXCR4 1403:1414 arg1 interaction 1416:1426 CXCL12-CXCR4 interaction 1403:1426 CXCL12-CXCR4 interaction 1403:1426 These dimeric CXCR4 modulators represent new molecular probes and therapeutics that effectively modulate CXCL12-CXCR4 interaction and function. 27658790 3 6 theme established 498:508 arg1 platform 510:517 our well established platform 489:517 our well established platform of chemistry and bioassays for CXCR4 489:554 This study presents the design and synthesis of a series of [PEG]n linked dimeric ligands of CXCR4 based on the knowledge of the homodimeric crystal structure of CXCR4 and our well established platform of chemistry and bioassays for CXCR4. 27658790 5 7 theme <50nM 949:953 arg1 values 939:944 IC50 values 934:944 IC50 values 934:944 Among a total of 24 peptide ligands, four antagonists and three agonists showed good CXCR4 binding affinity, with IC50 values of <50nM and <800nM, respectively. 27658790 6 8 theme homodimeric 1128:1138 arg1 DV3 1140:1142 homodimeric DV3 1128:1142 homodimeric DV3 1128:1142 Chemotaxis and calcium mobilization assays with SUP-T1 cells further identified two promising lead modulators of CXCR4: ligand 4, a [PEG3]2 linked homodimeric DV3, was an effective CXCR4 antagonist (IC50=22nM); and ligand 21, a [PEG3]2 linked heterodimeric DV3-CXCL121-8, was an effective CXCR4 agonist (IC50=407nM). 27658790 3 9 dep linked 384:389 arg1 n 382:382 n 382:382 n 382:382 This study presents the design and synthesis of a series of [PEG]n linked dimeric ligands of CXCR4 based on the knowledge of the homodimeric crystal structure of CXCR4 and our well established platform of chemistry and bioassays for CXCR4. 27658790 3 9 dep linked 384:389 arg1 [PEG 377:380 [PEG 377:380 [PEG 377:380 This study presents the design and synthesis of a series of [PEG]n linked dimeric ligands of CXCR4 based on the knowledge of the homodimeric crystal structure of CXCR4 and our well established platform of chemistry and bioassays for CXCR4. 27658790 3 10 theme bioassays 536:544 arg1 platform 510:517 our well established platform 489:517 our well established platform of chemistry and bioassays for CXCR4 489:554 This study presents the design and synthesis of a series of [PEG]n linked dimeric ligands of CXCR4 based on the knowledge of the homodimeric crystal structure of CXCR4 and our well established platform of chemistry and bioassays for CXCR4. 27658790 3 10 theme bioassays 536:544 arg1 CXCR4 479:483 CXCR4 479:483 CXCR4 479:483 This study presents the design and synthesis of a series of [PEG]n linked dimeric ligands of CXCR4 based on the knowledge of the homodimeric crystal structure of CXCR4 and our well established platform of chemistry and bioassays for CXCR4. 27658790 4 11 theme modules 736:742 arg1 DV3 688:690 DV3 688:690 DV3 688:690 These new ligands include [PEG]n linked homodimeric or heterodimeric peptides consisting of either two DV3-derived moieties (where DV3 is an all-d-amino acid analog of N-terminal modules of 1-10 (V3) residues of vMIP-II) or hybrids of DV3 moieties and CXCL121-8. 27658790 4 11 theme modules 736:742 arg1 analog 715:720 an all-d-amino acid analog 695:720 an all-d-amino acid analog of N-terminal modules of 1-10 (V3) residues of vMIP-II 695:775 These new ligands include [PEG]n linked homodimeric or heterodimeric peptides consisting of either two DV3-derived moieties (where DV3 is an all-d-amino acid analog of N-terminal modules of 1-10 (V3) residues of vMIP-II) or hybrids of DV3 moieties and CXCL121-8. 27658790 6 12 theme effective 1152:1160 arg1 ligand 1101:1106 ligand 4 1101:1108 ligand 4 1101:1108 Chemotaxis and calcium mobilization assays with SUP-T1 cells further identified two promising lead modulators of CXCR4: ligand 4, a [PEG3]2 linked homodimeric DV3, was an effective CXCR4 antagonist (IC50=22nM); and ligand 21, a [PEG3]2 linked heterodimeric DV3-CXCL121-8, was an effective CXCR4 agonist (IC50=407nM). 27658790 6 12 theme effective 1152:1160 arg1 IC50=22nM 1180:1188 IC50=22nM 1180:1188 IC50=22nM 1180:1188 Chemotaxis and calcium mobilization assays with SUP-T1 cells further identified two promising lead modulators of CXCR4: ligand 4, a [PEG3]2 linked homodimeric DV3, was an effective CXCR4 antagonist (IC50=22nM); and ligand 21, a [PEG3]2 linked heterodimeric DV3-CXCL121-8, was an effective CXCR4 agonist (IC50=407nM). 27658790 6 12 theme effective 1152:1160 arg1 antagonist 1168:1177 an effective CXCR4 antagonist 1149:1177 an effective CXCR4 antagonist (IC50=22nM) 1149:1189 Chemotaxis and calcium mobilization assays with SUP-T1 cells further identified two promising lead modulators of CXCR4: ligand 4, a [PEG3]2 linked homodimeric DV3, was an effective CXCR4 antagonist (IC50=22nM); and ligand 21, a [PEG3]2 linked heterodimeric DV3-CXCL121-8, was an effective CXCR4 agonist (IC50=407nM). 27658790 4 13 theme 1-10 747:750 arg1 vMIP-II 769:775 vMIP-II 769:775 vMIP-II 769:775 These new ligands include [PEG]n linked homodimeric or heterodimeric peptides consisting of either two DV3-derived moieties (where DV3 is an all-d-amino acid analog of N-terminal modules of 1-10 (V3) residues of vMIP-II) or hybrids of DV3 moieties and CXCL121-8. 27658790 4 13 theme 1-10 747:750 arg1 residues 757:764 1-10 (V3) residues 747:764 1-10 (V3) residues of vMIP-II 747:775 These new ligands include [PEG]n linked homodimeric or heterodimeric peptides consisting of either two DV3-derived moieties (where DV3 is an all-d-amino acid analog of N-terminal modules of 1-10 (V3) residues of vMIP-II) or hybrids of DV3 moieties and CXCL121-8. 27658790 4 14 theme acid 710:713 arg1 DV3 688:690 DV3 688:690 DV3 688:690 These new ligands include [PEG]n linked homodimeric or heterodimeric peptides consisting of either two DV3-derived moieties (where DV3 is an all-d-amino acid analog of N-terminal modules of 1-10 (V3) residues of vMIP-II) or hybrids of DV3 moieties and CXCL121-8. 27658790 4 14 theme acid 710:713 arg1 analog 715:720 an all-d-amino acid analog 695:720 an all-d-amino acid analog of N-terminal modules of 1-10 (V3) residues of vMIP-II 695:775 These new ligands include [PEG]n linked homodimeric or heterodimeric peptides consisting of either two DV3-derived moieties (where DV3 is an all-d-amino acid analog of N-terminal modules of 1-10 (V3) residues of vMIP-II) or hybrids of DV3 moieties and CXCL121-8. 27658790 4 15 theme heterodimeric 612:624 arg1 peptides 626:633 [PEG]n linked homodimeric or heterodimeric peptides 583:633 [PEG]n linked homodimeric or heterodimeric peptides consisting of either two DV3-derived moieties (where DV3 is an all-d-amino acid analog of N-terminal modules of 1-10 (V3) residues of vMIP-II) or hybrids of DV3 moieties and CXCL121-8 583:817 These new ligands include [PEG]n linked homodimeric or heterodimeric peptides consisting of either two DV3-derived moieties (where DV3 is an all-d-amino acid analog of N-terminal modules of 1-10 (V3) residues of vMIP-II) or hybrids of DV3 moieties and CXCL121-8. 27658790 3 16 theme chemistry 522:530 arg1 platform 510:517 our well established platform 489:517 our well established platform of chemistry and bioassays for CXCR4 489:554 This study presents the design and synthesis of a series of [PEG]n linked dimeric ligands of CXCR4 based on the knowledge of the homodimeric crystal structure of CXCR4 and our well established platform of chemistry and bioassays for CXCR4. 27658790 3 16 theme chemistry 522:530 arg1 CXCR4 479:483 CXCR4 479:483 CXCR4 479:483 This study presents the design and synthesis of a series of [PEG]n linked dimeric ligands of CXCR4 based on the knowledge of the homodimeric crystal structure of CXCR4 and our well established platform of chemistry and bioassays for CXCR4. 27658790 6 17 theme CXCR4 1162:1166 arg1 ligand 1101:1106 ligand 4 1101:1108 ligand 4 1101:1108 Chemotaxis and calcium mobilization assays with SUP-T1 cells further identified two promising lead modulators of CXCR4: ligand 4, a [PEG3]2 linked homodimeric DV3, was an effective CXCR4 antagonist (IC50=22nM); and ligand 21, a [PEG3]2 linked heterodimeric DV3-CXCL121-8, was an effective CXCR4 agonist (IC50=407nM). 27658790 6 17 theme CXCR4 1162:1166 arg1 IC50=22nM 1180:1188 IC50=22nM 1180:1188 IC50=22nM 1180:1188 Chemotaxis and calcium mobilization assays with SUP-T1 cells further identified two promising lead modulators of CXCR4: ligand 4, a [PEG3]2 linked homodimeric DV3, was an effective CXCR4 antagonist (IC50=22nM); and ligand 21, a [PEG3]2 linked heterodimeric DV3-CXCL121-8, was an effective CXCR4 agonist (IC50=407nM). 27658790 6 17 theme CXCR4 1162:1166 arg1 antagonist 1168:1177 an effective CXCR4 antagonist 1149:1177 an effective CXCR4 antagonist (IC50=22nM) 1149:1189 Chemotaxis and calcium mobilization assays with SUP-T1 cells further identified two promising lead modulators of CXCR4: ligand 4, a [PEG3]2 linked homodimeric DV3, was an effective CXCR4 antagonist (IC50=22nM); and ligand 21, a [PEG3]2 linked heterodimeric DV3-CXCL121-8, was an effective CXCR4 agonist (IC50=407nM). 27658790 3 18 theme series 367:372 arg1 synthesis 352:360 synthesis 352:360 synthesis 352:360 This study presents the design and synthesis of a series of [PEG]n linked dimeric ligands of CXCR4 based on the knowledge of the homodimeric crystal structure of CXCR4 and our well established platform of chemistry and bioassays for CXCR4. 27658790 3 18 theme series 367:372 arg1 design 341:346 design 341:346 design 341:346 This study presents the design and synthesis of a series of [PEG]n linked dimeric ligands of CXCR4 based on the knowledge of the homodimeric crystal structure of CXCR4 and our well established platform of chemistry and bioassays for CXCR4. 27658790 7 19 theme new 1339:1341 arg1 probes 1353:1358 new molecular probes 1339:1358 new molecular probes 1339:1358 These dimeric CXCR4 modulators represent new molecular probes and therapeutics that effectively modulate CXCL12-CXCR4 interaction and function. 27658790 3 20 theme CXCR4 410:414 arg1 ligands 399:405 [PEG]n linked dimeric ligands 377:405 [PEG]n linked dimeric ligands of CXCR4 based on the knowledge of the homodimeric crystal structure of CXCR4 and our well established platform of chemistry and bioassays for CXCR4 377:554 This study presents the design and synthesis of a series of [PEG]n linked dimeric ligands of CXCR4 based on the knowledge of the homodimeric crystal structure of CXCR4 and our well established platform of chemistry and bioassays for CXCR4. 27658790 7 21 theme CXCR4 1312:1316 arg1 modulators 1318:1327 These dimeric CXCR4 modulators 1298:1327 These dimeric CXCR4 modulators 1298:1327 These dimeric CXCR4 modulators represent new molecular probes and therapeutics that effectively modulate CXCL12-CXCR4 interaction and function. 27658790 7 22 theme molecular 1343:1351 arg1 probes 1353:1358 new molecular probes 1339:1358 new molecular probes 1339:1358 These dimeric CXCR4 modulators represent new molecular probes and therapeutics that effectively modulate CXCL12-CXCR4 interaction and function. 27658790 3 23 theme linked 384:389 arg1 ligands 399:405 [PEG]n linked dimeric ligands 377:405 [PEG]n linked dimeric ligands of CXCR4 based on the knowledge of the homodimeric crystal structure of CXCR4 and our well established platform of chemistry and bioassays for CXCR4 377:554 This study presents the design and synthesis of a series of [PEG]n linked dimeric ligands of CXCR4 based on the knowledge of the homodimeric crystal structure of CXCR4 and our well established platform of chemistry and bioassays for CXCR4. 27658790 6 24 theme effective 1260:1268 arg1 IC50=407nM 1285:1294 IC50=407nM 1285:1294 IC50=407nM 1285:1294 Chemotaxis and calcium mobilization assays with SUP-T1 cells further identified two promising lead modulators of CXCR4: ligand 4, a [PEG3]2 linked homodimeric DV3, was an effective CXCR4 antagonist (IC50=22nM); and ligand 21, a [PEG3]2 linked heterodimeric DV3-CXCL121-8, was an effective CXCR4 agonist (IC50=407nM). 27658790 6 24 theme effective 1260:1268 arg1 agonist 1276:1282 an effective CXCR4 agonist 1257:1282 an effective CXCR4 agonist (IC50=407nM) 1257:1295 Chemotaxis and calcium mobilization assays with SUP-T1 cells further identified two promising lead modulators of CXCR4: ligand 4, a [PEG3]2 linked homodimeric DV3, was an effective CXCR4 antagonist (IC50=22nM); and ligand 21, a [PEG3]2 linked heterodimeric DV3-CXCL121-8, was an effective CXCR4 agonist (IC50=407nM). 27658790 6 24 theme effective 1260:1268 arg1 ligand 1196:1201 ligand 21 1196:1204 ligand 21 1196:1204 Chemotaxis and calcium mobilization assays with SUP-T1 cells further identified two promising lead modulators of CXCR4: ligand 4, a [PEG3]2 linked homodimeric DV3, was an effective CXCR4 antagonist (IC50=22nM); and ligand 21, a [PEG3]2 linked heterodimeric DV3-CXCL121-8, was an effective CXCR4 agonist (IC50=407nM). 27658790 4 25 theme N-terminal 725:734 arg1 modules 736:742 N-terminal modules 725:742 N-terminal modules of 1-10 (V3) residues of vMIP-II 725:775 These new ligands include [PEG]n linked homodimeric or heterodimeric peptides consisting of either two DV3-derived moieties (where DV3 is an all-d-amino acid analog of N-terminal modules of 1-10 (V3) residues of vMIP-II) or hybrids of DV3 moieties and CXCL121-8. 27658790 3 26 theme dimeric 391:397 arg1 ligands 399:405 [PEG]n linked dimeric ligands 377:405 [PEG]n linked dimeric ligands of CXCR4 based on the knowledge of the homodimeric crystal structure of CXCR4 and our well established platform of chemistry and bioassays for CXCR4 377:554 This study presents the design and synthesis of a series of [PEG]n linked dimeric ligands of CXCR4 based on the knowledge of the homodimeric crystal structure of CXCR4 and our well established platform of chemistry and bioassays for CXCR4. 27658790 4 27 theme CXCL121-8 809:817 arg1 hybrids 781:787 hybrids 781:787 hybrids of DV3 moieties and CXCL121-8 781:817 These new ligands include [PEG]n linked homodimeric or heterodimeric peptides consisting of either two DV3-derived moieties (where DV3 is an all-d-amino acid analog of N-terminal modules of 1-10 (V3) residues of vMIP-II) or hybrids of DV3 moieties and CXCL121-8. 27658790 4 27 theme CXCL121-8 809:817 arg1 moieties 672:679 two DV3-derived moieties 656:679 two DV3-derived moieties (where DV3 is an all-d-amino acid analog of N-terminal modules of 1-10 (V3) residues of vMIP-II) 656:776 These new ligands include [PEG]n linked homodimeric or heterodimeric peptides consisting of either two DV3-derived moieties (where DV3 is an all-d-amino acid analog of N-terminal modules of 1-10 (V3) residues of vMIP-II) or hybrids of DV3 moieties and CXCL121-8. 27658790 4 28 theme DV3-derived 660:670 arg1 moieties 672:679 two DV3-derived moieties 656:679 two DV3-derived moieties (where DV3 is an all-d-amino acid analog of N-terminal modules of 1-10 (V3) residues of vMIP-II) 656:776 These new ligands include [PEG]n linked homodimeric or heterodimeric peptides consisting of either two DV3-derived moieties (where DV3 is an all-d-amino acid analog of N-terminal modules of 1-10 (V3) residues of vMIP-II) or hybrids of DV3 moieties and CXCL121-8. 27658790 3 29 dep design 341:346 arg1 the 337:339 the 337:339 the 337:339 This study presents the design and synthesis of a series of [PEG]n linked dimeric ligands of CXCR4 based on the knowledge of the homodimeric crystal structure of CXCR4 and our well established platform of chemistry and bioassays for CXCR4. 27658790 5 30 theme good 900:903 arg1 affinity 919:926 good CXCR4 binding affinity 900:926 good CXCR4 binding affinity 900:926 Among a total of 24 peptide ligands, four antagonists and three agonists showed good CXCR4 binding affinity, with IC50 values of <50nM and <800nM, respectively. 27658790 5 31 theme CXCR4 905:909 arg1 affinity 919:926 good CXCR4 binding affinity 900:926 good CXCR4 binding affinity 900:926 Among a total of 24 peptide ligands, four antagonists and three agonists showed good CXCR4 binding affinity, with IC50 values of <50nM and <800nM, respectively. 27658790 3 32 theme crystal 458:464 arg1 structure 466:474 the homodimeric crystal structure 442:474 the homodimeric crystal structure of CXCR4 and our well established platform of chemistry and bioassays for CXCR4 442:554 This study presents the design and synthesis of a series of [PEG]n linked dimeric ligands of CXCR4 based on the knowledge of the homodimeric crystal structure of CXCR4 and our well established platform of chemistry and bioassays for CXCR4. 27658790 6 33 theme promising 1065:1073 arg1 modulators 1080:1089 two promising lead modulators 1061:1089 two promising lead modulators of CXCR4 1061:1098 Chemotaxis and calcium mobilization assays with SUP-T1 cells further identified two promising lead modulators of CXCR4: ligand 4, a [PEG3]2 linked homodimeric DV3, was an effective CXCR4 antagonist (IC50=22nM); and ligand 21, a [PEG3]2 linked heterodimeric DV3-CXCL121-8, was an effective CXCR4 agonist (IC50=407nM). 27658790 4 34 theme new 563:565 arg1 ligands 567:573 These new ligands 557:573 These new ligands 557:573 These new ligands include [PEG]n linked homodimeric or heterodimeric peptides consisting of either two DV3-derived moieties (where DV3 is an all-d-amino acid analog of N-terminal modules of 1-10 (V3) residues of vMIP-II) or hybrids of DV3 moieties and CXCL121-8. 27658790 7 35 theme dimeric 1304:1310 arg1 modulators 1318:1327 These dimeric CXCR4 modulators 1298:1327 These dimeric CXCR4 modulators 1298:1327 These dimeric CXCR4 modulators represent new molecular probes and therapeutics that effectively modulate CXCL12-CXCR4 interaction and function. 27658790 6 36 with assays 1017:1022 arg1 cells 1036:1040 SUP-T1 cells 1029:1040 SUP-T1 cells 1029:1040 Chemotaxis and calcium mobilization assays with SUP-T1 cells further identified two promising lead modulators of CXCR4: ligand 4, a [PEG3]2 linked homodimeric DV3, was an effective CXCR4 antagonist (IC50=22nM); and ligand 21, a [PEG3]2 linked heterodimeric DV3-CXCL121-8, was an effective CXCR4 agonist (IC50=407nM). 27658790 1 37 theme CXCR4 101:105 arg1 dimerization 107:118 CXCR4 dimerization 101:118 CXCR4 dimerization 101:118 CXCR4 dimerization has been widely demonstrated both biologically and structurally. 27658790 3 38 theme structure 466:474 arg1 knowledge 429:437 the knowledge 425:437 the knowledge of the homodimeric crystal structure of CXCR4 and our well established platform of chemistry and bioassays for CXCR4 425:554 This study presents the design and synthesis of a series of [PEG]n linked dimeric ligands of CXCR4 based on the knowledge of the homodimeric crystal structure of CXCR4 and our well established platform of chemistry and bioassays for CXCR4. 27658790 0 39 theme biological 23:32 arg1 characterization 34:49 biological characterization 23:49 biological characterization 23:49 Design, synthesis, and biological characterization of novel PEG-linked dimeric modulators for CXCR4. 27658790 5 40 theme binding 911:917 arg1 affinity 919:926 good CXCR4 binding affinity 900:926 good CXCR4 binding affinity 900:926 Among a total of 24 peptide ligands, four antagonists and three agonists showed good CXCR4 binding affinity, with IC50 values of <50nM and <800nM, respectively. 27658790 2 41 theme dimeric 249:255 arg1 ligands 257:263 structure-based dimeric ligands 233:263 structure-based dimeric ligands that target CXCL12-CXCR4 interaction and signaling 233:314 This paper mainly focused on the development of structure-based dimeric ligands that target CXCL12-CXCR4 interaction and signaling. 27658790 6 42 theme mobilization 1004:1015 arg1 assays 1017:1022 Chemotaxis and calcium mobilization assays 981:1022 Chemotaxis and calcium mobilization assays with SUP-T1 cells 981:1040 Chemotaxis and calcium mobilization assays with SUP-T1 cells further identified two promising lead modulators of CXCR4: ligand 4, a [PEG3]2 linked homodimeric DV3, was an effective CXCR4 antagonist (IC50=22nM); and ligand 21, a [PEG3]2 linked heterodimeric DV3-CXCL121-8, was an effective CXCR4 agonist (IC50=407nM). 27658790 6 43 theme Chemotaxis 981:990 arg1 assays 1017:1022 Chemotaxis and calcium mobilization assays 981:1022 Chemotaxis and calcium mobilization assays with SUP-T1 cells 981:1040 Chemotaxis and calcium mobilization assays with SUP-T1 cells further identified two promising lead modulators of CXCR4: ligand 4, a [PEG3]2 linked homodimeric DV3, was an effective CXCR4 antagonist (IC50=22nM); and ligand 21, a [PEG3]2 linked heterodimeric DV3-CXCL121-8, was an effective CXCR4 agonist (IC50=407nM). 27658790 6 44 theme SUP-T1 1029:1034 arg1 cells 1036:1040 SUP-T1 cells 1029:1040 SUP-T1 cells 1029:1040 Chemotaxis and calcium mobilization assays with SUP-T1 cells further identified two promising lead modulators of CXCR4: ligand 4, a [PEG3]2 linked homodimeric DV3, was an effective CXCR4 antagonist (IC50=22nM); and ligand 21, a [PEG3]2 linked heterodimeric DV3-CXCL121-8, was an effective CXCR4 agonist (IC50=407nM). 27658790 4 45 link linked 590:595 arg1 peptides 626:633 [PEG]n linked homodimeric or heterodimeric peptides 583:633 [PEG]n linked homodimeric or heterodimeric peptides consisting of either two DV3-derived moieties (where DV3 is an all-d-amino acid analog of N-terminal modules of 1-10 (V3) residues of vMIP-II) or hybrids of DV3 moieties and CXCL121-8 583:817 These new ligands include [PEG]n linked homodimeric or heterodimeric peptides consisting of either two DV3-derived moieties (where DV3 is an all-d-amino acid analog of N-terminal modules of 1-10 (V3) residues of vMIP-II) or hybrids of DV3 moieties and CXCL121-8. 27658790 2 46 theme structure-based 233:247 arg1 ligands 257:263 structure-based dimeric ligands 233:263 structure-based dimeric ligands that target CXCL12-CXCR4 interaction and signaling 233:314 This paper mainly focused on the development of structure-based dimeric ligands that target CXCL12-CXCR4 interaction and signaling. 27658790 3 47 theme homodimeric 446:456 arg1 structure 466:474 the homodimeric crystal structure 442:474 the homodimeric crystal structure of CXCR4 and our well established platform of chemistry and bioassays for CXCR4 442:554 This study presents the design and synthesis of a series of [PEG]n linked dimeric ligands of CXCR4 based on the knowledge of the homodimeric crystal structure of CXCR4 and our well established platform of chemistry and bioassays for CXCR4. 27658790 3 48 theme ligands 399:405 arg1 series 367:372 a series 365:372 a series of [PEG]n linked dimeric ligands of CXCR4 based on the knowledge of the homodimeric crystal structure of CXCR4 and our well established platform of chemistry and bioassays for CXCR4 365:554 This study presents the design and synthesis of a series of [PEG]n linked dimeric ligands of CXCR4 based on the knowledge of the homodimeric crystal structure of CXCR4 and our well established platform of chemistry and bioassays for CXCR4. 27658790 4 49 theme DV3 792:794 arg1 moieties 796:803 DV3 moieties 792:803 DV3 moieties 792:803 These new ligands include [PEG]n linked homodimeric or heterodimeric peptides consisting of either two DV3-derived moieties (where DV3 is an all-d-amino acid analog of N-terminal modules of 1-10 (V3) residues of vMIP-II) or hybrids of DV3 moieties and CXCL121-8. 27658790 4 50 theme all-d-amino 698:708 arg1 DV3 688:690 DV3 688:690 DV3 688:690 These new ligands include [PEG]n linked homodimeric or heterodimeric peptides consisting of either two DV3-derived moieties (where DV3 is an all-d-amino acid analog of N-terminal modules of 1-10 (V3) residues of vMIP-II) or hybrids of DV3 moieties and CXCL121-8. 27658790 4 50 theme all-d-amino 698:708 arg1 analog 715:720 an all-d-amino acid analog 695:720 an all-d-amino acid analog of N-terminal modules of 1-10 (V3) residues of vMIP-II 695:775 These new ligands include [PEG]n linked homodimeric or heterodimeric peptides consisting of either two DV3-derived moieties (where DV3 is an all-d-amino acid analog of N-terminal modules of 1-10 (V3) residues of vMIP-II) or hybrids of DV3 moieties and CXCL121-8. 27658790 6 51 theme heterodimeric 1224:1236 arg1 DV3-CXCL121-8 1238:1250 heterodimeric DV3-CXCL121-8 1224:1250 heterodimeric DV3-CXCL121-8 1224:1250 Chemotaxis and calcium mobilization assays with SUP-T1 cells further identified two promising lead modulators of CXCR4: ligand 4, a [PEG3]2 linked homodimeric DV3, was an effective CXCR4 antagonist (IC50=22nM); and ligand 21, a [PEG3]2 linked heterodimeric DV3-CXCL121-8, was an effective CXCR4 agonist (IC50=407nM). 27658790 4 52 theme moieties 796:803 arg1 hybrids 781:787 hybrids 781:787 hybrids of DV3 moieties and CXCL121-8 781:817 These new ligands include [PEG]n linked homodimeric or heterodimeric peptides consisting of either two DV3-derived moieties (where DV3 is an all-d-amino acid analog of N-terminal modules of 1-10 (V3) residues of vMIP-II) or hybrids of DV3 moieties and CXCL121-8. 27658790 4 52 theme moieties 796:803 arg1 moieties 672:679 two DV3-derived moieties 656:679 two DV3-derived moieties (where DV3 is an all-d-amino acid analog of N-terminal modules of 1-10 (V3) residues of vMIP-II) 656:776 These new ligands include [PEG]n linked homodimeric or heterodimeric peptides consisting of either two DV3-derived moieties (where DV3 is an all-d-amino acid analog of N-terminal modules of 1-10 (V3) residues of vMIP-II) or hybrids of DV3 moieties and CXCL121-8. 27658790 0 53 link PEG-linked 60:69 arg1 modulators 79:88 novel PEG-linked dimeric modulators 54:88 novel PEG-linked dimeric modulators for CXCR4 54:98 Design, synthesis, and biological characterization of novel PEG-linked dimeric modulators for CXCR4. 27658790 4 54 theme vMIP-II 769:775 arg1 vMIP-II 769:775 vMIP-II 769:775 vMIP-II 769:775 These new ligands include [PEG]n linked homodimeric or heterodimeric peptides consisting of either two DV3-derived moieties (where DV3 is an all-d-amino acid analog of N-terminal modules of 1-10 (V3) residues of vMIP-II) or hybrids of DV3 moieties and CXCL121-8. 27658790 4 54 theme vMIP-II 769:775 arg1 residues 757:764 1-10 (V3) residues 747:764 1-10 (V3) residues of vMIP-II 747:775 These new ligands include [PEG]n linked homodimeric or heterodimeric peptides consisting of either two DV3-derived moieties (where DV3 is an all-d-amino acid analog of N-terminal modules of 1-10 (V3) residues of vMIP-II) or hybrids of DV3 moieties and CXCL121-8. 27658790 5 55 theme <800nM 959:964 arg1 values 939:944 IC50 values 934:944 IC50 values 934:944 Among a total of 24 peptide ligands, four antagonists and three agonists showed good CXCR4 binding affinity, with IC50 values of <50nM and <800nM, respectively. 27658790 4 56 dep moieties 672:679 arg1 DV3 688:690 DV3 688:690 DV3 688:690 These new ligands include [PEG]n linked homodimeric or heterodimeric peptides consisting of either two DV3-derived moieties (where DV3 is an all-d-amino acid analog of N-terminal modules of 1-10 (V3) residues of vMIP-II) or hybrids of DV3 moieties and CXCL121-8. 27658790 4 56 dep moieties 672:679 arg1 analog 715:720 an all-d-amino acid analog 695:720 an all-d-amino acid analog of N-terminal modules of 1-10 (V3) residues of vMIP-II 695:775 These new ligands include [PEG]n linked homodimeric or heterodimeric peptides consisting of either two DV3-derived moieties (where DV3 is an all-d-amino acid analog of N-terminal modules of 1-10 (V3) residues of vMIP-II) or hybrids of DV3 moieties and CXCL121-8. 27658790 2 57 theme CXCL12-CXCR4 277:288 arg1 interaction 290:300 CXCL12-CXCR4 interaction 277:300 CXCL12-CXCR4 interaction 277:300 This paper mainly focused on the development of structure-based dimeric ligands that target CXCL12-CXCR4 interaction and signaling. 27658790 4 58 link DV3-derived 660:670 arg1 moieties 672:679 two DV3-derived moieties 656:679 two DV3-derived moieties (where DV3 is an all-d-amino acid analog of N-terminal modules of 1-10 (V3) residues of vMIP-II) 656:776 These new ligands include [PEG]n linked homodimeric or heterodimeric peptides consisting of either two DV3-derived moieties (where DV3 is an all-d-amino acid analog of N-terminal modules of 1-10 (V3) residues of vMIP-II) or hybrids of DV3 moieties and CXCL121-8. 27658790 6 59 theme lead 1075:1078 arg1 modulators 1080:1089 two promising lead modulators 1061:1089 two promising lead modulators of CXCR4 1061:1098 Chemotaxis and calcium mobilization assays with SUP-T1 cells further identified two promising lead modulators of CXCR4: ligand 4, a [PEG3]2 linked homodimeric DV3, was an effective CXCR4 antagonist (IC50=22nM); and ligand 21, a [PEG3]2 linked heterodimeric DV3-CXCL121-8, was an effective CXCR4 agonist (IC50=407nM). 27658790 4 60 theme linked 590:595 arg1 peptides 626:633 [PEG]n linked homodimeric or heterodimeric peptides 583:633 [PEG]n linked homodimeric or heterodimeric peptides consisting of either two DV3-derived moieties (where DV3 is an all-d-amino acid analog of N-terminal modules of 1-10 (V3) residues of vMIP-II) or hybrids of DV3 moieties and CXCL121-8 583:817 These new ligands include [PEG]n linked homodimeric or heterodimeric peptides consisting of either two DV3-derived moieties (where DV3 is an all-d-amino acid analog of N-terminal modules of 1-10 (V3) residues of vMIP-II) or hybrids of DV3 moieties and CXCL121-8. 27658790 4 61 dep linked 590:595 arg1 [PEG 583:586 [PEG 583:586 [PEG 583:586 These new ligands include [PEG]n linked homodimeric or heterodimeric peptides consisting of either two DV3-derived moieties (where DV3 is an all-d-amino acid analog of N-terminal modules of 1-10 (V3) residues of vMIP-II) or hybrids of DV3 moieties and CXCL121-8. 27658790 4 61 dep linked 590:595 arg1 n 588:588 n 588:588 n 588:588 These new ligands include [PEG]n linked homodimeric or heterodimeric peptides consisting of either two DV3-derived moieties (where DV3 is an all-d-amino acid analog of N-terminal modules of 1-10 (V3) residues of vMIP-II) or hybrids of DV3 moieties and CXCL121-8. 27658790 4 62 theme residues 757:764 arg1 modules 736:742 N-terminal modules 725:742 N-terminal modules of 1-10 (V3) residues of vMIP-II 725:775 These new ligands include [PEG]n linked homodimeric or heterodimeric peptides consisting of either two DV3-derived moieties (where DV3 is an all-d-amino acid analog of N-terminal modules of 1-10 (V3) residues of vMIP-II) or hybrids of DV3 moieties and CXCL121-8. 27658790 3 63 theme CXCR4 479:483 arg1 structure 466:474 the homodimeric crystal structure 442:474 the homodimeric crystal structure of CXCR4 and our well established platform of chemistry and bioassays for CXCR4 442:554 This study presents the design and synthesis of a series of [PEG]n linked dimeric ligands of CXCR4 based on the knowledge of the homodimeric crystal structure of CXCR4 and our well established platform of chemistry and bioassays for CXCR4. 27658790 0 64 theme PEG-linked 60:69 arg1 modulators 79:88 novel PEG-linked dimeric modulators 54:88 novel PEG-linked dimeric modulators for CXCR4 54:98 Design, synthesis, and biological characterization of novel PEG-linked dimeric modulators for CXCR4. 27658790 3 65 link linked 384:389 arg1 ligands 399:405 [PEG]n linked dimeric ligands 377:405 [PEG]n linked dimeric ligands of CXCR4 based on the knowledge of the homodimeric crystal structure of CXCR4 and our well established platform of chemistry and bioassays for CXCR4 377:554 This study presents the design and synthesis of a series of [PEG]n linked dimeric ligands of CXCR4 based on the knowledge of the homodimeric crystal structure of CXCR4 and our well established platform of chemistry and bioassays for CXCR4. 27658790 6 66 theme calcium 996:1002 arg1 mobilization 1004:1015 calcium mobilization 996:1015 calcium mobilization 996:1015 Chemotaxis and calcium mobilization assays with SUP-T1 cells further identified two promising lead modulators of CXCR4: ligand 4, a [PEG3]2 linked homodimeric DV3, was an effective CXCR4 antagonist (IC50=22nM); and ligand 21, a [PEG3]2 linked heterodimeric DV3-CXCL121-8, was an effective CXCR4 agonist (IC50=407nM). 27658790 3 67 theme platform 510:517 arg1 structure 466:474 the homodimeric crystal structure 442:474 the homodimeric crystal structure of CXCR4 and our well established platform of chemistry and bioassays for CXCR4 442:554 This study presents the design and synthesis of a series of [PEG]n linked dimeric ligands of CXCR4 based on the knowledge of the homodimeric crystal structure of CXCR4 and our well established platform of chemistry and bioassays for CXCR4. 27658790 0 68 theme novel 54:58 arg1 modulators 79:88 novel PEG-linked dimeric modulators 54:88 novel PEG-linked dimeric modulators for CXCR4 54:98 Design, synthesis, and biological characterization of novel PEG-linked dimeric modulators for CXCR4. 27658790 6 69 theme CXCR4 1094:1098 arg1 modulators 1080:1089 two promising lead modulators 1061:1089 two promising lead modulators of CXCR4 1061:1098 Chemotaxis and calcium mobilization assays with SUP-T1 cells further identified two promising lead modulators of CXCR4: ligand 4, a [PEG3]2 linked homodimeric DV3, was an effective CXCR4 antagonist (IC50=22nM); and ligand 21, a [PEG3]2 linked heterodimeric DV3-CXCL121-8, was an effective CXCR4 agonist (IC50=407nM). 27658790 2 70 theme ligands 257:263 arg1 development 218:228 the development 214:228 the development of structure-based dimeric ligands that target CXCL12-CXCR4 interaction and signaling 214:314 This paper mainly focused on the development of structure-based dimeric ligands that target CXCL12-CXCR4 interaction and signaling. 27658790 5 71 theme peptide 840:846 arg1 ligands 848:854 24 peptide ligands 837:854 24 peptide ligands 837:854 Among a total of 24 peptide ligands, four antagonists and three agonists showed good CXCR4 binding affinity, with IC50 values of <50nM and <800nM, respectively. 27658790 4 72 theme homodimeric 597:607 arg1 peptides 626:633 [PEG]n linked homodimeric or heterodimeric peptides 583:633 [PEG]n linked homodimeric or heterodimeric peptides consisting of either two DV3-derived moieties (where DV3 is an all-d-amino acid analog of N-terminal modules of 1-10 (V3) residues of vMIP-II) or hybrids of DV3 moieties and CXCL121-8 583:817 These new ligands include [PEG]n linked homodimeric or heterodimeric peptides consisting of either two DV3-derived moieties (where DV3 is an all-d-amino acid analog of N-terminal modules of 1-10 (V3) residues of vMIP-II) or hybrids of DV3 moieties and CXCL121-8. 25700084 6 0 theme FlaB2S2 1039:1045 arg1 proteins 1047:1054 all mutated FlaB2S2 proteins 1027:1054 all mutated FlaB2S2 proteins 1027:1054 Western blot results showed that all mutated FlaB2S2 proteins were expressed and of smaller apparent molecular mass compared to wildtype FlaB2S2, consistent with the loss of glycosylation sites. 25700084 10 1 theme glycosylation 1632:1644 arg1 amount 1611:1616 some minimum amount 1598:1616 some minimum amount of archaellin glycosylation 1598:1644 Elimination of all 4 N-glycosylation sites resulted in non-archaellated cells, indicating some minimum amount of archaellin glycosylation was necessary for their incorporation into stable archaella. 25700084 10 1 theme glycosylation 1632:1644 arg1 glycosylation 1632:1644 archaellin glycosylation 1621:1644 archaellin glycosylation 1621:1644 Elimination of all 4 N-glycosylation sites resulted in non-archaellated cells, indicating some minimum amount of archaellin glycosylation was necessary for their incorporation into stable archaella. 25700084 7 2 gly glycosylation 1332:1344 arg2 site 1346:1349 the 1st to 4th glycosylation site 1317:1349 the 1st to 4th glycosylation site 1317:1349 In the 8 single-site mutant complements, archaella were observed on the surface of Q2, D2 and D4 (numbers after N or Q refer to the 1st to 4th glycosylation site). 25700084 7 3 theme 4th 1328:1330 arg1 site 1346:1349 the 1st to 4th glycosylation site 1317:1349 the 1st to 4th glycosylation site 1317:1349 In the 8 single-site mutant complements, archaella were observed on the surface of Q2, D2 and D4 (numbers after N or Q refer to the 1st to 4th glycosylation site). 25700084 12 4 theme ΔflaB2S2 1976:1983 arg1 strain 1985:1990 the ΔflaB2S2 strain 1972:1990 the ΔflaB2S2 strain 1972:1990 In addition, a series of FlaB2S2 scanning deletions each missing 10 amino acids was also generated and tested for their ability to complement the ΔflaB2S2 strain. 25700084 6 5 theme wildtype 1122:1129 arg1 FlaB2S2 1131:1137 wildtype FlaB2S2 1122:1137 wildtype FlaB2S2 1122:1137 Western blot results showed that all mutated FlaB2S2 proteins were expressed and of smaller apparent molecular mass compared to wildtype FlaB2S2, consistent with the loss of glycosylation sites. 25700084 4 6 theme possible 655:662 arg1 combinations 664:675 all possible combinations 651:675 all possible combinations 651:675 Here, we explored the potential requirement of N-glycosylation of archaellins on archaellation by investigating the effects of eliminating the 4 N-glycosylation sites in the wildtype FlaB2S2 protein in all possible combinations either by Asn to Glu (N to Q) substitution or Asn to Asp (N to D) substitutions of the N-glycosylation sequon asparagine. 25700084 6 7 gly glycosylation 1168:1180 arg2 sites 1182:1186 glycosylation sites 1168:1186 glycosylation sites 1168:1186 Western blot results showed that all mutated FlaB2S2 proteins were expressed and of smaller apparent molecular mass compared to wildtype FlaB2S2, consistent with the loss of glycosylation sites. 25700084 2 8 from sites 332:336 arg1 tetrasaccharide 304:318 an N-linked tetrasaccharide 292:318 an N-linked tetrasaccharide at multiple sites 292:336 All three are modified with an N-linked tetrasaccharide at multiple sites. 25700084 11 9 with cells 1786:1790 arg1 exception 1801:1809 the exception 1797:1809 the exception of the D4 version 1797:1827 All complementations that led to a return of archaella also resulted in motile cells with the exception of the D4 version. 25700084 5 10 theme derivatives 827:837 arg1 ability 803:809 The ability 799:809 The ability of these mutant derivatives to complement a non-archaellated ΔflaB2S2 strain 799:886 The ability of these mutant derivatives to complement a non-archaellated ΔflaB2S2 strain was examined by electron microscopy (for archaella assembly) and swarm plates (for analysis of swimming). 25700084 6 11 theme molecular 1095:1103 arg1 mass 1105:1108 smaller apparent molecular mass 1078:1108 smaller apparent molecular mass compared to wildtype FlaB2S2 1078:1137 Western blot results showed that all mutated FlaB2S2 proteins were expressed and of smaller apparent molecular mass compared to wildtype FlaB2S2, consistent with the loss of glycosylation sites. 25700084 4 12 theme FlaB2S2 632:638 arg1 protein 640:646 the wildtype FlaB2S2 protein 619:646 the wildtype FlaB2S2 protein 619:646 Here, we explored the potential requirement of N-glycosylation of archaellins on archaellation by investigating the effects of eliminating the 4 N-glycosylation sites in the wildtype FlaB2S2 protein in all possible combinations either by Asn to Glu (N to Q) substitution or Asn to Asp (N to D) substitutions of the N-glycosylation sequon asparagine. 25700084 11 13 theme D4 1818:1819 arg1 version 1821:1827 the D4 version 1814:1827 the D4 version 1814:1827 All complementations that led to a return of archaella also resulted in motile cells with the exception of the D4 version. 25700084 11 14 theme archaella 1752:1760 arg1 return 1742:1747 a return 1740:1747 a return of archaella 1740:1760 All complementations that led to a return of archaella also resulted in motile cells with the exception of the D4 version. 25700084 7 15 located observed 1245:1252 arg2 archaella 1230:1238 archaella 1230:1238 archaella 1230:1238 In the 8 single-site mutant complements, archaella were observed on the surface of Q2, D2 and D4 (numbers after N or Q refer to the 1st to 4th glycosylation site). 25700084 7 15 located observed 1245:1252 arg1 complements 1217:1227 the 8 single-site mutant complements 1192:1227 the 8 single-site mutant complements 1192:1227 In the 8 single-site mutant complements, archaella were observed on the surface of Q2, D2 and D4 (numbers after N or Q refer to the 1st to 4th glycosylation site). 25700084 7 15 located observed 1245:1252 arg1 surface 1261:1267 the surface 1257:1267 the surface of Q2, D2 and D4 (numbers after N or Q refer to the 1st to 4th glycosylation site) 1257:1350 In the 8 single-site mutant complements, archaella were observed on the surface of Q2, D2 and D4 (numbers after N or Q refer to the 1st to 4th glycosylation site). 25700084 12 16 theme scanning 1863:1870 arg1 deletions 1872:1880 FlaB2S2 scanning deletions 1855:1880 FlaB2S2 scanning deletions each missing 10 amino acids 1855:1908 In addition, a series of FlaB2S2 scanning deletions each missing 10 amino acids was also generated and tested for their ability to complement the ΔflaB2S2 strain. 25700084 6 17 theme glycosylation 1168:1180 arg1 sites 1182:1186 glycosylation sites 1168:1186 glycosylation sites 1168:1186 Western blot results showed that all mutated FlaB2S2 proteins were expressed and of smaller apparent molecular mass compared to wildtype FlaB2S2, consistent with the loss of glycosylation sites. 25700084 4 18 theme N 699:699 arg1 Glu 694:696 Glu 694:696 Glu (N to Q) substitution 694:718 Here, we explored the potential requirement of N-glycosylation of archaellins on archaellation by investigating the effects of eliminating the 4 N-glycosylation sites in the wildtype FlaB2S2 protein in all possible combinations either by Asn to Glu (N to Q) substitution or Asn to Asp (N to D) substitutions of the N-glycosylation sequon asparagine. 25700084 4 18 theme N 699:699 arg1 Q 704:704 N to Q 699:704 N to Q 699:704 Here, we explored the potential requirement of N-glycosylation of archaellins on archaellation by investigating the effects of eliminating the 4 N-glycosylation sites in the wildtype FlaB2S2 protein in all possible combinations either by Asn to Glu (N to Q) substitution or Asn to Asp (N to D) substitutions of the N-glycosylation sequon asparagine. 25700084 7 19 theme D4 1283:1284 arg1 surface 1261:1267 the surface 1257:1267 the surface of Q2, D2 and D4 (numbers after N or Q refer to the 1st to 4th glycosylation site) 1257:1350 In the 8 single-site mutant complements, archaella were observed on the surface of Q2, D2 and D4 (numbers after N or Q refer to the 1st to 4th glycosylation site). 25700084 9 20 theme only 1478:1481 arg1 D2,3,4 1483:1488 only D2,3,4 1478:1488 only D2,3,4 1478:1488 Of the 4 triple-site mutation complements, only D2,3,4 was archaellated. 25700084 3 21 link N-linked 357:364 arg1 pathway 380:386 the N-linked glycosylation pathway 353:386 the N-linked glycosylation pathway 353:386 Disruption of the N-linked glycosylation pathway is known to cause defects in archaella assembly or function. 25700084 8 22 theme double-site 1362:1372 arg1 complementations 1383:1398 the 6 double-site mutation complementations 1356:1398 the 6 double-site mutation complementations 1356:1398 Of the 6 double-site mutation complementations all were archaellated except D1,3. 25700084 7 23 theme D2 1276:1277 arg1 surface 1261:1267 the surface 1257:1267 the surface of Q2, D2 and D4 (numbers after N or Q refer to the 1st to 4th glycosylation site) 1257:1350 In the 8 single-site mutant complements, archaella were observed on the surface of Q2, D2 and D4 (numbers after N or Q refer to the 1st to 4th glycosylation site). 25700084 11 24 theme version 1821:1827 arg1 exception 1801:1809 the exception 1797:1809 the exception of the D4 version 1797:1827 All complementations that led to a return of archaella also resulted in motile cells with the exception of the D4 version. 25700084 4 25 theme potential 471:479 arg1 requirement 481:491 the potential requirement 467:491 the potential requirement of N-glycosylation of archaellins on archaellation 467:542 Here, we explored the potential requirement of N-glycosylation of archaellins on archaellation by investigating the effects of eliminating the 4 N-glycosylation sites in the wildtype FlaB2S2 protein in all possible combinations either by Asn to Glu (N to Q) substitution or Asn to Asp (N to D) substitutions of the N-glycosylation sequon asparagine. 25700084 4 26 theme Glu 694:696 arg1 substitution 707:718 Glu (N to Q) substitution 694:718 Glu (N to Q) substitution 694:718 Here, we explored the potential requirement of N-glycosylation of archaellins on archaellation by investigating the effects of eliminating the 4 N-glycosylation sites in the wildtype FlaB2S2 protein in all possible combinations either by Asn to Glu (N to Q) substitution or Asn to Asp (N to D) substitutions of the N-glycosylation sequon asparagine. 25700084 4 27 gly N-glycosylation 594:608 arg2 sites 610:614 the 4 N-glycosylation sites 588:614 the 4 N-glycosylation sites in the wildtype FlaB2S2 protein 588:646 Here, we explored the potential requirement of N-glycosylation of archaellins on archaellation by investigating the effects of eliminating the 4 N-glycosylation sites in the wildtype FlaB2S2 protein in all possible combinations either by Asn to Glu (N to Q) substitution or Asn to Asp (N to D) substitutions of the N-glycosylation sequon asparagine. 25700084 4 27 gly N-glycosylation 594:608 arg2 4 592:592 4 592:592 4 592:592 Here, we explored the potential requirement of N-glycosylation of archaellins on archaellation by investigating the effects of eliminating the 4 N-glycosylation sites in the wildtype FlaB2S2 protein in all possible combinations either by Asn to Glu (N to Q) substitution or Asn to Asp (N to D) substitutions of the N-glycosylation sequon asparagine. 25700084 5 28 theme non-archaellated 855:870 arg1 strain 881:886 a non-archaellated ΔflaB2S2 strain 853:886 a non-archaellated ΔflaB2S2 strain 853:886 The ability of these mutant derivatives to complement a non-archaellated ΔflaB2S2 strain was examined by electron microscopy (for archaella assembly) and swarm plates (for analysis of swimming). 25700084 6 29 with consistent 1140:1149 arg1 loss 1160:1163 the loss 1156:1163 the loss of glycosylation sites 1156:1186 Western blot results showed that all mutated FlaB2S2 proteins were expressed and of smaller apparent molecular mass compared to wildtype FlaB2S2, consistent with the loss of glycosylation sites. 25700084 0 30 from Effects 0:6 arg1 function 75:82 function 75:82 function 75:82 Effects of N-glycosylation site removal in archaellins on the assembly and function of archaella in Methanococcus maripaludis. 25700084 0 30 from Effects 0:6 arg1 archaellins 43:53 archaellins 43:53 archaellins 43:53 Effects of N-glycosylation site removal in archaellins on the assembly and function of archaella in Methanococcus maripaludis. 25700084 0 30 from Effects 0:6 arg1 assembly 62:69 assembly 62:69 assembly 62:69 Effects of N-glycosylation site removal in archaellins on the assembly and function of archaella in Methanococcus maripaludis. 25700084 10 31 gly N-glycosylation 1529:1543 arg2 sites 1545:1549 all 4 N-glycosylation sites 1523:1549 all 4 N-glycosylation sites 1523:1549 Elimination of all 4 N-glycosylation sites resulted in non-archaellated cells, indicating some minimum amount of archaellin glycosylation was necessary for their incorporation into stable archaella. 25700084 10 31 gly N-glycosylation 1529:1543 arg2 4 1527:1527 4 1527:1527 4 1527:1527 Elimination of all 4 N-glycosylation sites resulted in non-archaellated cells, indicating some minimum amount of archaellin glycosylation was necessary for their incorporation into stable archaella. 25700084 4 32 theme Asp 730:732 arg1 substitutions 743:755 Asp (N to D) substitutions 730:755 Asp (N to D) substitutions of the N-glycosylation sequon asparagine 730:796 Here, we explored the potential requirement of N-glycosylation of archaellins on archaellation by investigating the effects of eliminating the 4 N-glycosylation sites in the wildtype FlaB2S2 protein in all possible combinations either by Asn to Glu (N to Q) substitution or Asn to Asp (N to D) substitutions of the N-glycosylation sequon asparagine. 25700084 5 33 theme archaella 929:937 arg1 assembly 939:946 archaella assembly 929:946 archaella assembly 929:946 The ability of these mutant derivatives to complement a non-archaellated ΔflaB2S2 strain was examined by electron microscopy (for archaella assembly) and swarm plates (for analysis of swimming). 25700084 0 34 from archaellins 43:53 arg1 Effects 0:6 Effects 0:6 Effects of N-glycosylation site removal in archaellins on the assembly and function of archaella in Methanococcus maripaludis. 0:125 Effects of N-glycosylation site removal in archaellins on the assembly and function of archaella in Methanococcus maripaludis. 25700084 4 35 theme N 735:735 arg1 Asp 730:732 Asp 730:732 Asp (N to D) substitutions of the N-glycosylation sequon asparagine 730:796 Here, we explored the potential requirement of N-glycosylation of archaellins on archaellation by investigating the effects of eliminating the 4 N-glycosylation sites in the wildtype FlaB2S2 protein in all possible combinations either by Asn to Glu (N to Q) substitution or Asn to Asp (N to D) substitutions of the N-glycosylation sequon asparagine. 25700084 4 35 theme N 735:735 arg1 D 740:740 N to D 735:740 N to D 735:740 Here, we explored the potential requirement of N-glycosylation of archaellins on archaellation by investigating the effects of eliminating the 4 N-glycosylation sites in the wildtype FlaB2S2 protein in all possible combinations either by Asn to Glu (N to Q) substitution or Asn to Asp (N to D) substitutions of the N-glycosylation sequon asparagine. 25700084 3 36 theme archaella 417:425 arg1 assembly 427:434 archaella assembly 417:434 archaella assembly 417:434 Disruption of the N-linked glycosylation pathway is known to cause defects in archaella assembly or function. 25700084 4 37 dep investigating 547:559 arg1 either 677:682 either 677:682 either 677:682 Here, we explored the potential requirement of N-glycosylation of archaellins on archaellation by investigating the effects of eliminating the 4 N-glycosylation sites in the wildtype FlaB2S2 protein in all possible combinations either by Asn to Glu (N to Q) substitution or Asn to Asp (N to D) substitutions of the N-glycosylation sequon asparagine. 25700084 9 38 theme mutation 1456:1463 arg1 complements 1465:1475 the 4 triple-site mutation complements 1438:1475 the 4 triple-site mutation complements 1438:1475 Of the 4 triple-site mutation complements, only D2,3,4 was archaellated. 25700084 3 39 theme glycosylation 366:378 arg1 pathway 380:386 the N-linked glycosylation pathway 353:386 the N-linked glycosylation pathway 353:386 Disruption of the N-linked glycosylation pathway is known to cause defects in archaella assembly or function. 25700084 0 40 from removal 32:38 arg1 archaellins 43:53 archaellins 43:53 archaellins 43:53 Effects of N-glycosylation site removal in archaellins on the assembly and function of archaella in Methanococcus maripaludis. 25700084 5 41 theme electron 904:911 arg1 microscopy 913:922 electron microscopy 904:922 electron microscopy (for archaella assembly) 904:947 The ability of these mutant derivatives to complement a non-archaellated ΔflaB2S2 strain was examined by electron microscopy (for archaella assembly) and swarm plates (for analysis of swimming). 25700084 0 42 theme N-glycosylation 11:25 arg1 removal 32:38 N-glycosylation site removal 11:38 N-glycosylation site removal in archaellins 11:53 Effects of N-glycosylation site removal in archaellins on the assembly and function of archaella in Methanococcus maripaludis. 25700084 7 43 theme 1st 1321:1323 arg1 site 1346:1349 the 1st to 4th glycosylation site 1317:1349 the 1st to 4th glycosylation site 1317:1349 In the 8 single-site mutant complements, archaella were observed on the surface of Q2, D2 and D4 (numbers after N or Q refer to the 1st to 4th glycosylation site). 25700084 6 44 theme Western 994:1000 arg1 results 1007:1013 Western blot results 994:1013 Western blot results 994:1013 Western blot results showed that all mutated FlaB2S2 proteins were expressed and of smaller apparent molecular mass compared to wildtype FlaB2S2, consistent with the loss of glycosylation sites. 25700084 0 45 theme removal 32:38 arg1 Effects 0:6 Effects 0:6 Effects of N-glycosylation site removal in archaellins on the assembly and function of archaella in Methanococcus maripaludis. 0:125 Effects of N-glycosylation site removal in archaellins on the assembly and function of archaella in Methanococcus maripaludis. 25700084 13 46 theme smaller 2096:2102 arg1 deletion 2117:2124 a smaller 3-amino acid deletion 2094:2124 a smaller 3-amino acid deletion 2094:2124 While most variants were expressed, none of them restored archaellation, although FlaB2S2 harbouring a smaller 3-amino acid deletion was able to partially restore archaellation. 25700084 4 47 theme sequon 780:785 arg1 asparagine 787:796 the N-glycosylation sequon asparagine 760:796 the N-glycosylation sequon asparagine 760:796 Here, we explored the potential requirement of N-glycosylation of archaellins on archaellation by investigating the effects of eliminating the 4 N-glycosylation sites in the wildtype FlaB2S2 protein in all possible combinations either by Asn to Glu (N to Q) substitution or Asn to Asp (N to D) substitutions of the N-glycosylation sequon asparagine. 25700084 2 48 theme multiple 323:330 arg1 sites 332:336 multiple sites 323:336 multiple sites 323:336 All three are modified with an N-linked tetrasaccharide at multiple sites. 25700084 13 49 theme acid 2112:2115 arg1 deletion 2117:2124 a smaller 3-amino acid deletion 2094:2124 a smaller 3-amino acid deletion 2094:2124 While most variants were expressed, none of them restored archaellation, although FlaB2S2 harbouring a smaller 3-amino acid deletion was able to partially restore archaellation. 25700084 5 50 theme swimming 983:990 arg1 analysis 971:978 analysis 971:978 analysis of swimming 971:990 The ability of these mutant derivatives to complement a non-archaellated ΔflaB2S2 strain was examined by electron microscopy (for archaella assembly) and swarm plates (for analysis of swimming). 25700084 5 51 theme swarm 953:957 arg1 plates 959:964 swarm plates 953:964 swarm plates (for analysis of swimming) 953:991 The ability of these mutant derivatives to complement a non-archaellated ΔflaB2S2 strain was examined by electron microscopy (for archaella assembly) and swarm plates (for analysis of swimming). 25700084 4 52 theme N-glycosylation 594:608 arg1 sites 610:614 the 4 N-glycosylation sites 588:614 the 4 N-glycosylation sites in the wildtype FlaB2S2 protein 588:646 Here, we explored the potential requirement of N-glycosylation of archaellins on archaellation by investigating the effects of eliminating the 4 N-glycosylation sites in the wildtype FlaB2S2 protein in all possible combinations either by Asn to Glu (N to Q) substitution or Asn to Asp (N to D) substitutions of the N-glycosylation sequon asparagine. 25700084 7 53 theme single-site 1198:1208 arg1 complements 1217:1227 the 8 single-site mutant complements 1192:1227 the 8 single-site mutant complements 1192:1227 In the 8 single-site mutant complements, archaella were observed on the surface of Q2, D2 and D4 (numbers after N or Q refer to the 1st to 4th glycosylation site). 25700084 2 54 link N-linked 295:302 arg1 tetrasaccharide 304:318 an N-linked tetrasaccharide 292:318 an N-linked tetrasaccharide at multiple sites 292:336 All three are modified with an N-linked tetrasaccharide at multiple sites. 25700084 4 55 from N-glycosylation 496:510 arg1 archaellation 530:542 archaellation 530:542 archaellation 530:542 Here, we explored the potential requirement of N-glycosylation of archaellins on archaellation by investigating the effects of eliminating the 4 N-glycosylation sites in the wildtype FlaB2S2 protein in all possible combinations either by Asn to Glu (N to Q) substitution or Asn to Asp (N to D) substitutions of the N-glycosylation sequon asparagine. 25700084 13 56 theme them 2037:2040 arg1 none 2029:2032 none 2029:2032 none of them 2029:2040 While most variants were expressed, none of them restored archaellation, although FlaB2S2 harbouring a smaller 3-amino acid deletion was able to partially restore archaellation. 25700084 6 57 theme mutated 1031:1037 arg1 proteins 1047:1054 all mutated FlaB2S2 proteins 1027:1054 all mutated FlaB2S2 proteins 1027:1054 Western blot results showed that all mutated FlaB2S2 proteins were expressed and of smaller apparent molecular mass compared to wildtype FlaB2S2, consistent with the loss of glycosylation sites. 25700084 0 58 gly N-glycosylation 11:25 arg2 site 27:30 N-glycosylation site removal 11:38 N-glycosylation site removal in archaellins 11:53 Effects of N-glycosylation site removal in archaellins on the assembly and function of archaella in Methanococcus maripaludis. 25700084 0 58 gly N-glycosylation 11:25 arg2 removal 32:38 N-glycosylation site removal 11:38 N-glycosylation site removal in archaellins 11:53 Effects of N-glycosylation site removal in archaellins on the assembly and function of archaella in Methanococcus maripaludis. 25700084 10 59 theme stable 1689:1694 arg1 archaella 1696:1704 stable archaella 1689:1704 stable archaella 1689:1704 Elimination of all 4 N-glycosylation sites resulted in non-archaellated cells, indicating some minimum amount of archaellin glycosylation was necessary for their incorporation into stable archaella. 25700084 12 60 theme amino 1898:1902 arg1 acids 1904:1908 10 amino acids 1895:1908 10 amino acids 1895:1908 In addition, a series of FlaB2S2 scanning deletions each missing 10 amino acids was also generated and tested for their ability to complement the ΔflaB2S2 strain. 25700084 7 61 theme glycosylation 1332:1344 arg1 site 1346:1349 the 1st to 4th glycosylation site 1317:1349 the 1st to 4th glycosylation site 1317:1349 In the 8 single-site mutant complements, archaella were observed on the surface of Q2, D2 and D4 (numbers after N or Q refer to the 1st to 4th glycosylation site). 25700084 10 62 theme archaellin 1621:1630 arg1 glycosylation 1632:1644 archaellin glycosylation 1621:1644 archaellin glycosylation 1621:1644 Elimination of all 4 N-glycosylation sites resulted in non-archaellated cells, indicating some minimum amount of archaellin glycosylation was necessary for their incorporation into stable archaella. 25700084 4 63 dep D 740:740 arg1 to 737:738 to 737:738 to 737:738 Here, we explored the potential requirement of N-glycosylation of archaellins on archaellation by investigating the effects of eliminating the 4 N-glycosylation sites in the wildtype FlaB2S2 protein in all possible combinations either by Asn to Glu (N to Q) substitution or Asn to Asp (N to D) substitutions of the N-glycosylation sequon asparagine. 25700084 1 64 theme swimming 164:171 arg1 organelle 173:181 the swimming organelle 160:181 the swimming organelle 160:181 In Methanococcus maripaludis S2, the swimming organelle, the archaellum, is composed of three archaellins, FlaB1S2, FlaB2S2 and FlaB3S2. 25700084 1 64 theme swimming 164:171 arg1 archaellum 188:197 the archaellum 184:197 the archaellum 184:197 In Methanococcus maripaludis S2, the swimming organelle, the archaellum, is composed of three archaellins, FlaB1S2, FlaB2S2 and FlaB3S2. 25700084 4 65 theme asparagine 787:796 arg1 substitutions 743:755 Asp (N to D) substitutions 730:755 Asp (N to D) substitutions of the N-glycosylation sequon asparagine 730:796 Here, we explored the potential requirement of N-glycosylation of archaellins on archaellation by investigating the effects of eliminating the 4 N-glycosylation sites in the wildtype FlaB2S2 protein in all possible combinations either by Asn to Glu (N to Q) substitution or Asn to Asp (N to D) substitutions of the N-glycosylation sequon asparagine. 25700084 4 66 gly N-glycosylation 496:510 arg1 archaellins 515:525 archaellins 515:525 archaellins on archaellation 515:542 Here, we explored the potential requirement of N-glycosylation of archaellins on archaellation by investigating the effects of eliminating the 4 N-glycosylation sites in the wildtype FlaB2S2 protein in all possible combinations either by Asn to Glu (N to Q) substitution or Asn to Asp (N to D) substitutions of the N-glycosylation sequon asparagine. 25700084 5 67 theme mutant 820:825 arg1 derivatives 827:837 these mutant derivatives 814:837 these mutant derivatives 814:837 The ability of these mutant derivatives to complement a non-archaellated ΔflaB2S2 strain was examined by electron microscopy (for archaella assembly) and swarm plates (for analysis of swimming). 25700084 12 68 theme deletions 1872:1880 arg1 series 1845:1850 a series 1843:1850 a series of FlaB2S2 scanning deletions each missing 10 amino acids 1843:1908 In addition, a series of FlaB2S2 scanning deletions each missing 10 amino acids was also generated and tested for their ability to complement the ΔflaB2S2 strain. 25700084 0 69 from function 75:82 arg1 maripaludis 114:124 Methanococcus maripaludis 100:124 Methanococcus maripaludis 100:124 Effects of N-glycosylation site removal in archaellins on the assembly and function of archaella in Methanococcus maripaludis. 25700084 6 70 theme apparent 1086:1093 arg1 mass 1105:1108 smaller apparent molecular mass 1078:1108 smaller apparent molecular mass compared to wildtype FlaB2S2 1078:1137 Western blot results showed that all mutated FlaB2S2 proteins were expressed and of smaller apparent molecular mass compared to wildtype FlaB2S2, consistent with the loss of glycosylation sites. 25700084 4 71 theme wildtype 623:630 arg1 protein 640:646 the wildtype FlaB2S2 protein 619:646 the wildtype FlaB2S2 protein 619:646 Here, we explored the potential requirement of N-glycosylation of archaellins on archaellation by investigating the effects of eliminating the 4 N-glycosylation sites in the wildtype FlaB2S2 protein in all possible combinations either by Asn to Glu (N to Q) substitution or Asn to Asp (N to D) substitutions of the N-glycosylation sequon asparagine. 25700084 10 72 theme N-glycosylation 1529:1543 arg1 sites 1545:1549 all 4 N-glycosylation sites 1523:1549 all 4 N-glycosylation sites 1523:1549 Elimination of all 4 N-glycosylation sites resulted in non-archaellated cells, indicating some minimum amount of archaellin glycosylation was necessary for their incorporation into stable archaella. 25700084 11 73 theme motile 1779:1784 arg1 cells 1786:1790 motile cells 1779:1790 motile cells with the exception of the D4 version 1779:1827 All complementations that led to a return of archaella also resulted in motile cells with the exception of the D4 version. 25700084 0 74 from assembly 62:69 arg1 maripaludis 114:124 Methanococcus maripaludis 100:124 Methanococcus maripaludis 100:124 Effects of N-glycosylation site removal in archaellins on the assembly and function of archaella in Methanococcus maripaludis. 25700084 6 75 theme sites 1182:1186 arg1 loss 1160:1163 the loss 1156:1163 the loss of glycosylation sites 1156:1186 Western blot results showed that all mutated FlaB2S2 proteins were expressed and of smaller apparent molecular mass compared to wildtype FlaB2S2, consistent with the loss of glycosylation sites. 25700084 5 76 theme ΔflaB2S2 872:879 arg1 strain 881:886 a non-archaellated ΔflaB2S2 strain 853:886 a non-archaellated ΔflaB2S2 strain 853:886 The ability of these mutant derivatives to complement a non-archaellated ΔflaB2S2 strain was examined by electron microscopy (for archaella assembly) and swarm plates (for analysis of swimming). 25700084 12 77 theme FlaB2S2 1855:1861 arg1 deletions 1872:1880 FlaB2S2 scanning deletions 1855:1880 FlaB2S2 scanning deletions each missing 10 amino acids 1855:1908 In addition, a series of FlaB2S2 scanning deletions each missing 10 amino acids was also generated and tested for their ability to complement the ΔflaB2S2 strain. 25700084 13 78 theme most 1999:2002 arg1 variants 2004:2011 most variants 1999:2011 most variants 1999:2011 While most variants were expressed, none of them restored archaellation, although FlaB2S2 harbouring a smaller 3-amino acid deletion was able to partially restore archaellation. 25700084 8 79 theme mutation 1374:1381 arg1 complementations 1383:1398 the 6 double-site mutation complementations 1356:1398 the 6 double-site mutation complementations 1356:1398 Of the 6 double-site mutation complementations all were archaellated except D1,3. 25700084 1 80 theme maripaludis 144:154 arg1 S2 156:157 Methanococcus maripaludis S2 130:157 Methanococcus maripaludis S2 130:157 In Methanococcus maripaludis S2, the swimming organelle, the archaellum, is composed of three archaellins, FlaB1S2, FlaB2S2 and FlaB3S2. 25700084 4 81 from sites 610:614 arg1 protein 640:646 the wildtype FlaB2S2 protein 619:646 the wildtype FlaB2S2 protein 619:646 Here, we explored the potential requirement of N-glycosylation of archaellins on archaellation by investigating the effects of eliminating the 4 N-glycosylation sites in the wildtype FlaB2S2 protein in all possible combinations either by Asn to Glu (N to Q) substitution or Asn to Asp (N to D) substitutions of the N-glycosylation sequon asparagine. 25700084 4 82 theme N-glycosylation 496:510 arg1 requirement 481:491 the potential requirement 467:491 the potential requirement of N-glycosylation of archaellins on archaellation 467:542 Here, we explored the potential requirement of N-glycosylation of archaellins on archaellation by investigating the effects of eliminating the 4 N-glycosylation sites in the wildtype FlaB2S2 protein in all possible combinations either by Asn to Glu (N to Q) substitution or Asn to Asp (N to D) substitutions of the N-glycosylation sequon asparagine. 25700084 0 83 theme archaella 87:95 arg1 function 75:82 function 75:82 function 75:82 Effects of N-glycosylation site removal in archaellins on the assembly and function of archaella in Methanococcus maripaludis. 25700084 0 83 theme archaella 87:95 arg1 assembly 62:69 assembly 62:69 assembly 62:69 Effects of N-glycosylation site removal in archaellins on the assembly and function of archaella in Methanococcus maripaludis. 25700084 10 84 theme minimum 1603:1609 arg1 amount 1611:1616 some minimum amount 1598:1616 some minimum amount of archaellin glycosylation 1598:1644 Elimination of all 4 N-glycosylation sites resulted in non-archaellated cells, indicating some minimum amount of archaellin glycosylation was necessary for their incorporation into stable archaella. 25700084 10 84 theme minimum 1603:1609 arg1 glycosylation 1632:1644 archaellin glycosylation 1621:1644 archaellin glycosylation 1621:1644 Elimination of all 4 N-glycosylation sites resulted in non-archaellated cells, indicating some minimum amount of archaellin glycosylation was necessary for their incorporation into stable archaella. 25700084 9 85 theme triple-site 1444:1454 arg1 complements 1465:1475 the 4 triple-site mutation complements 1438:1475 the 4 triple-site mutation complements 1438:1475 Of the 4 triple-site mutation complements, only D2,3,4 was archaellated. 25700084 7 86 theme Q2 1272:1273 arg1 surface 1261:1267 the surface 1257:1267 the surface of Q2, D2 and D4 (numbers after N or Q refer to the 1st to 4th glycosylation site) 1257:1350 In the 8 single-site mutant complements, archaella were observed on the surface of Q2, D2 and D4 (numbers after N or Q refer to the 1st to 4th glycosylation site). 25700084 2 87 mod modified 278:285 arg3 tetrasaccharide 304:318 an N-linked tetrasaccharide 292:318 an N-linked tetrasaccharide at multiple sites 292:336 All three are modified with an N-linked tetrasaccharide at multiple sites. 25700084 2 87 mod modified 278:285 arg1 three 268:272 three 268:272 three 268:272 All three are modified with an N-linked tetrasaccharide at multiple sites. 25700084 4 88 dep Q 704:704 arg1 to 701:702 to 701:702 to 701:702 Here, we explored the potential requirement of N-glycosylation of archaellins on archaellation by investigating the effects of eliminating the 4 N-glycosylation sites in the wildtype FlaB2S2 protein in all possible combinations either by Asn to Glu (N to Q) substitution or Asn to Asp (N to D) substitutions of the N-glycosylation sequon asparagine. 25700084 3 89 theme pathway 380:386 arg1 Disruption 339:348 Disruption 339:348 Disruption of the N-linked glycosylation pathway 339:386 Disruption of the N-linked glycosylation pathway is known to cause defects in archaella assembly or function. 25700084 12 90 dep deletions 1872:1880 arg1 each 1882:1885 each 1882:1885 each 1882:1885 In addition, a series of FlaB2S2 scanning deletions each missing 10 amino acids was also generated and tested for their ability to complement the ΔflaB2S2 strain. 25700084 10 91 theme sites 1545:1549 arg1 Elimination 1508:1518 Elimination 1508:1518 Elimination of all 4 N-glycosylation sites 1508:1549 Elimination of all 4 N-glycosylation sites resulted in non-archaellated cells, indicating some minimum amount of archaellin glycosylation was necessary for their incorporation into stable archaella. 25700084 0 92 theme site 27:30 arg1 removal 32:38 N-glycosylation site removal 11:38 N-glycosylation site removal in archaellins 11:53 Effects of N-glycosylation site removal in archaellins on the assembly and function of archaella in Methanococcus maripaludis. 25700084 0 93 dep assembly 62:69 arg1 the 58:60 the 58:60 the 58:60 Effects of N-glycosylation site removal in archaellins on the assembly and function of archaella in Methanococcus maripaludis. 25700084 6 94 theme blot 1002:1005 arg1 results 1007:1013 Western blot results 994:1013 Western blot results 994:1013 Western blot results showed that all mutated FlaB2S2 proteins were expressed and of smaller apparent molecular mass compared to wildtype FlaB2S2, consistent with the loss of glycosylation sites. 25700084 3 95 theme N-linked 357:364 arg1 pathway 380:386 the N-linked glycosylation pathway 353:386 the N-linked glycosylation pathway 353:386 Disruption of the N-linked glycosylation pathway is known to cause defects in archaella assembly or function. 25700084 4 96 from archaellation 530:542 arg1 N-glycosylation 496:510 N-glycosylation 496:510 N-glycosylation of archaellins on archaellation 496:542 Here, we explored the potential requirement of N-glycosylation of archaellins on archaellation by investigating the effects of eliminating the 4 N-glycosylation sites in the wildtype FlaB2S2 protein in all possible combinations either by Asn to Glu (N to Q) substitution or Asn to Asp (N to D) substitutions of the N-glycosylation sequon asparagine. 25700084 10 97 theme non-archaellated 1563:1578 arg1 cells 1580:1584 non-archaellated cells 1563:1584 non-archaellated cells 1563:1584 Elimination of all 4 N-glycosylation sites resulted in non-archaellated cells, indicating some minimum amount of archaellin glycosylation was necessary for their incorporation into stable archaella. 25700084 4 98 theme archaellins 515:525 arg1 N-glycosylation 496:510 N-glycosylation 496:510 N-glycosylation of archaellins on archaellation 496:542 Here, we explored the potential requirement of N-glycosylation of archaellins on archaellation by investigating the effects of eliminating the 4 N-glycosylation sites in the wildtype FlaB2S2 protein in all possible combinations either by Asn to Glu (N to Q) substitution or Asn to Asp (N to D) substitutions of the N-glycosylation sequon asparagine. 25700084 4 99 from archaellins 515:525 arg1 archaellation 530:542 archaellation 530:542 archaellation 530:542 Here, we explored the potential requirement of N-glycosylation of archaellins on archaellation by investigating the effects of eliminating the 4 N-glycosylation sites in the wildtype FlaB2S2 protein in all possible combinations either by Asn to Glu (N to Q) substitution or Asn to Asp (N to D) substitutions of the N-glycosylation sequon asparagine. 25700084 13 100 theme 3-amino 2104:2110 arg1 deletion 2117:2124 a smaller 3-amino acid deletion 2094:2124 a smaller 3-amino acid deletion 2094:2124 While most variants were expressed, none of them restored archaellation, although FlaB2S2 harbouring a smaller 3-amino acid deletion was able to partially restore archaellation. 25700084 7 101 dep Q2 1272:1273 arg1 numbers 1287:1293 numbers 1287:1293 numbers after N or Q refer to the 1st to 4th glycosylation site 1287:1349 In the 8 single-site mutant complements, archaella were observed on the surface of Q2, D2 and D4 (numbers after N or Q refer to the 1st to 4th glycosylation site). 25700084 6 102 theme smaller 1078:1084 arg1 mass 1105:1108 smaller apparent molecular mass 1078:1108 smaller apparent molecular mass compared to wildtype FlaB2S2 1078:1137 Western blot results showed that all mutated FlaB2S2 proteins were expressed and of smaller apparent molecular mass compared to wildtype FlaB2S2, consistent with the loss of glycosylation sites. 25700084 4 103 theme N-glycosylation 764:778 arg1 asparagine 787:796 the N-glycosylation sequon asparagine 760:796 the N-glycosylation sequon asparagine 760:796 Here, we explored the potential requirement of N-glycosylation of archaellins on archaellation by investigating the effects of eliminating the 4 N-glycosylation sites in the wildtype FlaB2S2 protein in all possible combinations either by Asn to Glu (N to Q) substitution or Asn to Asp (N to D) substitutions of the N-glycosylation sequon asparagine. 25700084 7 104 theme mutant 1210:1215 arg1 complements 1217:1227 the 8 single-site mutant complements 1192:1227 the 8 single-site mutant complements 1192:1227 In the 8 single-site mutant complements, archaella were observed on the surface of Q2, D2 and D4 (numbers after N or Q refer to the 1st to 4th glycosylation site). 25700084 3 105 from defects 406:412 arg1 function 439:446 function 439:446 function 439:446 Disruption of the N-linked glycosylation pathway is known to cause defects in archaella assembly or function. 25700084 3 105 from defects 406:412 arg1 assembly 427:434 archaella assembly 417:434 archaella assembly 417:434 Disruption of the N-linked glycosylation pathway is known to cause defects in archaella assembly or function. 25700084 2 106 theme N-linked 295:302 arg1 tetrasaccharide 304:318 an N-linked tetrasaccharide 292:318 an N-linked tetrasaccharide at multiple sites 292:336 All three are modified with an N-linked tetrasaccharide at multiple sites. 24519966 6 0 with substrates 1040:1049 arg1 reactivity 1073:1082 nearly identical reactivity 1056:1082 nearly identical reactivity 1056:1082 In this study, we revealed that this enzyme also accepts N-linked sugar chains with glucose moieties as substrates with nearly identical reactivity. 24519966 2 1 theme α1,2-mannosidase 345:360 arg1 ERManI 365:370 ERManI 365:370 ERManI 365:370 Upon exit from the calnexin/calreticulin cycle, glycoproteins are digested by α-mannosidases in the ER, especially α1,2-mannosidase I (ERManI). 24519966 2 1 theme α1,2-mannosidase 345:360 arg1 I 362:362 α1,2-mannosidase I 345:362 α1,2-mannosidase I (ERManI) 345:371 Upon exit from the calnexin/calreticulin cycle, glycoproteins are digested by α-mannosidases in the ER, especially α1,2-mannosidase I (ERManI). 24519966 2 1 theme α1,2-mannosidase 345:360 arg1 α-mannosidases 308:321 α-mannosidases 308:321 α-mannosidases in the ER 308:331 Upon exit from the calnexin/calreticulin cycle, glycoproteins are digested by α-mannosidases in the ER, especially α1,2-mannosidase I (ERManI). 24519966 3 2 link α1,2-linked 487:497 arg1 residues 507:514 two or more α1,2-linked mannose residues 475:514 two or more α1,2-linked mannose residues 475:514 ERManI removes the α1,2-linked mannose of the B-chain from properly folded ER glycoproteins, whereas two or more α1,2-linked mannose residues are sequentially trimmed from improperly folded glycoproteins so they are recognized by a complex that mediates ER-associated degradation (ERAD). 24519966 8 3 theme living 1451:1456 arg1 organisms 1458:1466 living organisms 1451:1466 living organisms 1451:1466 The properties of hERManI enable rapid selection of ERAD substrates in the ER and may help maintain homeostasis of sugar metabolism in living organisms. 24519966 4 4 theme In 836:837 arg1 trimming 853:860 In vitro mannose trimming 836:860 In vitro mannose trimming property of human ER α-1,2 mannosidase I. Glycoconj 836:912 We have shown that the efficiency of Man9GlcNAc2 de-mannosylation in model glycoproteins by recombinant human ERManI (hERManI) is dependent on folding status (Aikawa et al. (In vitro mannose trimming property of human ER α-1,2 mannosidase I. Glycoconj. 24519966 1 5 theme asparagine-linked 134:150 arg1 glycosylation 163:175 asparagine-linked (N-linked) glycosylation 134:175 asparagine-linked (N-linked) glycosylation 134:175 In the endoplasmic reticulum (ER), folding of proteins modified by asparagine-linked (N-linked) glycosylation is precisely monitored by quality control machinery. 24519966 2 6 from α-mannosidases 308:321 arg1 ER 330:331 the ER 326:331 the ER 326:331 Upon exit from the calnexin/calreticulin cycle, glycoproteins are digested by α-mannosidases in the ER, especially α1,2-mannosidase I (ERManI). 24519966 4 7 theme α-1,2 883:887 arg1 mannosidase 889:899 human ER α-1,2 mannosidase 874:899 human ER α-1,2 mannosidase 874:899 We have shown that the efficiency of Man9GlcNAc2 de-mannosylation in model glycoproteins by recombinant human ERManI (hERManI) is dependent on folding status (Aikawa et al. (In vitro mannose trimming property of human ER α-1,2 mannosidase I. Glycoconj. 24519966 3 8 from mannose 405:411 arg1 glycoproteins 452:464 properly folded ER glycoproteins 433:464 properly folded ER glycoproteins 433:464 ERManI removes the α1,2-linked mannose of the B-chain from properly folded ER glycoproteins, whereas two or more α1,2-linked mannose residues are sequentially trimmed from improperly folded glycoproteins so they are recognized by a complex that mediates ER-associated degradation (ERAD). 24519966 3 9 theme folded 557:562 arg1 glycoproteins 564:576 improperly folded glycoproteins 546:576 improperly folded glycoproteins so they are recognized by a complex that mediates ER-associated degradation (ERAD) 546:659 ERManI removes the α1,2-linked mannose of the B-chain from properly folded ER glycoproteins, whereas two or more α1,2-linked mannose residues are sequentially trimmed from improperly folded glycoproteins so they are recognized by a complex that mediates ER-associated degradation (ERAD). 24519966 2 10 gly glycoproteins 278:290 arg1 glycoproteins 278:290 glycoproteins 278:290 glycoproteins 278:290 Upon exit from the calnexin/calreticulin cycle, glycoproteins are digested by α-mannosidases in the ER, especially α1,2-mannosidase I (ERManI). 24519966 4 11 theme mannose 845:851 arg1 trimming 853:860 In vitro mannose trimming 836:860 In vitro mannose trimming property of human ER α-1,2 mannosidase I. Glycoconj 836:912 We have shown that the efficiency of Man9GlcNAc2 de-mannosylation in model glycoproteins by recombinant human ERManI (hERManI) is dependent on folding status (Aikawa et al. (In vitro mannose trimming property of human ER α-1,2 mannosidase I. Glycoconj. 24519966 3 12 dep glycoproteins 564:576 arg1 recognized 590:599 recognized 590:599 are recognized by a complex that mediates ER-associated degradation (ERAD) 586:659 ERManI removes the α1,2-linked mannose of the B-chain from properly folded ER glycoproteins, whereas two or more α1,2-linked mannose residues are sequentially trimmed from improperly folded glycoproteins so they are recognized by a complex that mediates ER-associated degradation (ERAD). 24519966 8 13 from selection 1355:1363 arg1 ER 1391:1392 the ER 1387:1392 the ER 1387:1392 The properties of hERManI enable rapid selection of ERAD substrates in the ER and may help maintain homeostasis of sugar metabolism in living organisms. 24519966 7 14 theme mannose 1118:1124 arg1 residues 1126:1133 mannose residues 1118:1133 mannose residues 1118:1133 The ability of hERManI to remove mannose residues from GlcMan9GlcNAc2 in model glycoproteins, such as Aspergillus oryzae β-galactosidase and chicken immunoglobulin Y (IgY), was markedly augmented when glycoproteins were denatured. 24519966 6 15 theme identical 1063:1071 arg1 reactivity 1073:1082 nearly identical reactivity 1056:1082 nearly identical reactivity 1056:1082 In this study, we revealed that this enzyme also accepts N-linked sugar chains with glucose moieties as substrates with nearly identical reactivity. 24519966 3 16 dep removes 381:387 arg1 whereas 467:473 whereas 467:473 whereas 467:473 ERManI removes the α1,2-linked mannose of the B-chain from properly folded ER glycoproteins, whereas two or more α1,2-linked mannose residues are sequentially trimmed from improperly folded glycoproteins so they are recognized by a complex that mediates ER-associated degradation (ERAD). 24519966 6 17 theme glucose 1020:1026 arg1 moieties 1028:1035 glucose moieties 1020:1035 glucose moieties 1020:1035 In this study, we revealed that this enzyme also accepts N-linked sugar chains with glucose moieties as substrates with nearly identical reactivity. 24519966 3 18 theme B-chain 420:426 arg1 mannose 405:411 the α1,2-linked mannose 389:411 the α1,2-linked mannose of the B-chain from properly folded ER glycoproteins 389:464 ERManI removes the α1,2-linked mannose of the B-chain from properly folded ER glycoproteins, whereas two or more α1,2-linked mannose residues are sequentially trimmed from improperly folded glycoproteins so they are recognized by a complex that mediates ER-associated degradation (ERAD). 24519966 4 19 dep In 836:837 arg1 vitro 839:843 vitro 839:843 vitro 839:843 We have shown that the efficiency of Man9GlcNAc2 de-mannosylation in model glycoproteins by recombinant human ERManI (hERManI) is dependent on folding status (Aikawa et al. (In vitro mannose trimming property of human ER α-1,2 mannosidase I. Glycoconj. 24519966 3 20 theme α1,2-linked 393:403 arg1 mannose 405:411 the α1,2-linked mannose 389:411 the α1,2-linked mannose of the B-chain from properly folded ER glycoproteins 389:464 ERManI removes the α1,2-linked mannose of the B-chain from properly folded ER glycoproteins, whereas two or more α1,2-linked mannose residues are sequentially trimmed from improperly folded glycoproteins so they are recognized by a complex that mediates ER-associated degradation (ERAD). 24519966 7 21 attach remove 1111:1116 arg1 GlcMan9GlcNAc2 1140:1153 GlcMan9GlcNAc2 1140:1153 GlcMan9GlcNAc2 in model glycoproteins, such as Aspergillus oryzae β-galactosidase and chicken immunoglobulin Y (IgY), 1140:1256 The ability of hERManI to remove mannose residues from GlcMan9GlcNAc2 in model glycoproteins, such as Aspergillus oryzae β-galactosidase and chicken immunoglobulin Y (IgY), was markedly augmented when glycoproteins were denatured. 24519966 7 21 attach remove 1111:1116 arg2 ability 1089:1095 The ability 1085:1095 The ability of hERManI to remove mannose residues from GlcMan9GlcNAc2 in model glycoproteins, such as Aspergillus oryzae β-galactosidase and chicken immunoglobulin Y (IgY), 1085:1256 The ability of hERManI to remove mannose residues from GlcMan9GlcNAc2 in model glycoproteins, such as Aspergillus oryzae β-galactosidase and chicken immunoglobulin Y (IgY), was markedly augmented when glycoproteins were denatured. 24519966 2 22 theme calnexin/calreticulin 249:269 arg1 cycle 271:275 the calnexin/calreticulin cycle 245:275 the calnexin/calreticulin cycle 245:275 Upon exit from the calnexin/calreticulin cycle, glycoproteins are digested by α-mannosidases in the ER, especially α1,2-mannosidase I (ERManI). 24519966 1 23 theme N-linked 153:160 arg1 glycosylation 163:175 asparagine-linked (N-linked) glycosylation 134:175 asparagine-linked (N-linked) glycosylation 134:175 In the endoplasmic reticulum (ER), folding of proteins modified by asparagine-linked (N-linked) glycosylation is precisely monitored by quality control machinery. 24519966 7 24 theme model 1158:1162 arg1 IgY 1252:1254 chicken immunoglobulin Y (IgY) 1226:1255 chicken immunoglobulin Y (IgY) 1226:1255 The ability of hERManI to remove mannose residues from GlcMan9GlcNAc2 in model glycoproteins, such as Aspergillus oryzae β-galactosidase and chicken immunoglobulin Y (IgY), was markedly augmented when glycoproteins were denatured. 24519966 7 24 theme model 1158:1162 arg1 glycoproteins 1164:1176 model glycoproteins 1158:1176 model glycoproteins 1158:1176 The ability of hERManI to remove mannose residues from GlcMan9GlcNAc2 in model glycoproteins, such as Aspergillus oryzae β-galactosidase and chicken immunoglobulin Y (IgY), was markedly augmented when glycoproteins were denatured. 24519966 7 24 theme model 1158:1162 arg1 β-galactosidase 1206:1220 Aspergillus oryzae β-galactosidase 1187:1220 Aspergillus oryzae β-galactosidase 1187:1220 The ability of hERManI to remove mannose residues from GlcMan9GlcNAc2 in model glycoproteins, such as Aspergillus oryzae β-galactosidase and chicken immunoglobulin Y (IgY), was markedly augmented when glycoproteins were denatured. 24519966 1 25 theme endoplasmic 74:84 arg1 reticulum 86:94 the endoplasmic reticulum 70:94 the endoplasmic reticulum (ER) 70:99 In the endoplasmic reticulum (ER), folding of proteins modified by asparagine-linked (N-linked) glycosylation is precisely monitored by quality control machinery. 24519966 1 25 theme endoplasmic 74:84 arg1 ER 97:98 ER 97:98 ER 97:98 In the endoplasmic reticulum (ER), folding of proteins modified by asparagine-linked (N-linked) glycosylation is precisely monitored by quality control machinery. 24519966 6 26 theme N-linked 993:1000 arg1 substrates 1040:1049 substrates 1040:1049 substrates with nearly identical reactivity 1040:1082 In this study, we revealed that this enzyme also accepts N-linked sugar chains with glucose moieties as substrates with nearly identical reactivity. 24519966 6 26 theme N-linked 993:1000 arg1 chains 1008:1013 N-linked sugar chains 993:1013 N-linked sugar chains 993:1013 In this study, we revealed that this enzyme also accepts N-linked sugar chains with glucose moieties as substrates with nearly identical reactivity. 24519966 1 27 link N-linked 153:160 arg1 glycosylation 163:175 asparagine-linked (N-linked) glycosylation 134:175 asparagine-linked (N-linked) glycosylation 134:175 In the endoplasmic reticulum (ER), folding of proteins modified by asparagine-linked (N-linked) glycosylation is precisely monitored by quality control machinery. 24519966 4 28 from glycoproteins 737:749 arg1 dependent 792:800 dependent 792:800 dependent 792:800 We have shown that the efficiency of Man9GlcNAc2 de-mannosylation in model glycoproteins by recombinant human ERManI (hERManI) is dependent on folding status (Aikawa et al. (In vitro mannose trimming property of human ER α-1,2 mannosidase I. Glycoconj. 24519966 4 28 from glycoproteins 737:749 arg1 efficiency 685:694 the efficiency 681:694 the efficiency of Man9GlcNAc2 de-mannosylation in model glycoproteins by recombinant human ERManI (hERManI) 681:787 We have shown that the efficiency of Man9GlcNAc2 de-mannosylation in model glycoproteins by recombinant human ERManI (hERManI) is dependent on folding status (Aikawa et al. (In vitro mannose trimming property of human ER α-1,2 mannosidase I. Glycoconj. 24519966 4 28 from glycoproteins 737:749 arg1 Aikawa 821:826 Aikawa 821:826 Aikawa 821:826 We have shown that the efficiency of Man9GlcNAc2 de-mannosylation in model glycoproteins by recombinant human ERManI (hERManI) is dependent on folding status (Aikawa et al. (In vitro mannose trimming property of human ER α-1,2 mannosidase I. Glycoconj. 24519966 4 29 theme model 731:735 arg1 glycoproteins 737:749 model glycoproteins 731:749 model glycoproteins 731:749 We have shown that the efficiency of Man9GlcNAc2 de-mannosylation in model glycoproteins by recombinant human ERManI (hERManI) is dependent on folding status (Aikawa et al. (In vitro mannose trimming property of human ER α-1,2 mannosidase I. Glycoconj. 24519966 0 30 theme N-glycans 25:33 arg1 Trimming 0:7 Trimming 0:7 Trimming of glucosylated N-glycans by human ER α1,2-mannosidase I. 0:65 Trimming of glucosylated N-glycans by human ER α1,2-mannosidase I. 24519966 6 31 theme sugar 1002:1006 arg1 substrates 1040:1049 substrates 1040:1049 substrates with nearly identical reactivity 1040:1082 In this study, we revealed that this enzyme also accepts N-linked sugar chains with glucose moieties as substrates with nearly identical reactivity. 24519966 6 31 theme sugar 1002:1006 arg1 chains 1008:1013 N-linked sugar chains 993:1013 N-linked sugar chains 993:1013 In this study, we revealed that this enzyme also accepts N-linked sugar chains with glucose moieties as substrates with nearly identical reactivity. 24519966 4 32 theme mannosidase 889:899 arg1 property 862:869 property 862:869 In vitro mannose trimming property of human ER α-1,2 mannosidase I. Glycoconj 836:912 We have shown that the efficiency of Man9GlcNAc2 de-mannosylation in model glycoproteins by recombinant human ERManI (hERManI) is dependent on folding status (Aikawa et al. (In vitro mannose trimming property of human ER α-1,2 mannosidase I. Glycoconj. 24519966 7 33 theme Aspergillus 1187:1197 arg1 oryzae 1199:1204 Aspergillus oryzae 1187:1204 Aspergillus oryzae β-galactosidase 1187:1220 The ability of hERManI to remove mannose residues from GlcMan9GlcNAc2 in model glycoproteins, such as Aspergillus oryzae β-galactosidase and chicken immunoglobulin Y (IgY), was markedly augmented when glycoproteins were denatured. 24519966 4 34 theme recombinant 754:764 arg1 ERManI 772:777 recombinant human ERManI 754:777 recombinant human ERManI (hERManI) 754:787 We have shown that the efficiency of Man9GlcNAc2 de-mannosylation in model glycoproteins by recombinant human ERManI (hERManI) is dependent on folding status (Aikawa et al. (In vitro mannose trimming property of human ER α-1,2 mannosidase I. Glycoconj. 24519966 4 34 theme recombinant 754:764 arg1 hERManI 780:786 hERManI 780:786 hERManI 780:786 We have shown that the efficiency of Man9GlcNAc2 de-mannosylation in model glycoproteins by recombinant human ERManI (hERManI) is dependent on folding status (Aikawa et al. (In vitro mannose trimming property of human ER α-1,2 mannosidase I. Glycoconj. 24519966 4 35 dep trimming 853:860 arg1 property 862:869 property 862:869 In vitro mannose trimming property of human ER α-1,2 mannosidase I. Glycoconj 836:912 We have shown that the efficiency of Man9GlcNAc2 de-mannosylation in model glycoproteins by recombinant human ERManI (hERManI) is dependent on folding status (Aikawa et al. (In vitro mannose trimming property of human ER α-1,2 mannosidase I. Glycoconj. 24519966 3 36 theme ER 449:450 arg1 glycoproteins 452:464 properly folded ER glycoproteins 433:464 properly folded ER glycoproteins 433:464 ERManI removes the α1,2-linked mannose of the B-chain from properly folded ER glycoproteins, whereas two or more α1,2-linked mannose residues are sequentially trimmed from improperly folded glycoproteins so they are recognized by a complex that mediates ER-associated degradation (ERAD). 24519966 0 37 theme glucosylated 12:23 arg1 N-glycans 25:33 glucosylated N-glycans 12:33 glucosylated N-glycans 12:33 Trimming of glucosylated N-glycans by human ER α1,2-mannosidase I. 24519966 1 38 link asparagine-linked 134:150 arg1 glycosylation 163:175 asparagine-linked (N-linked) glycosylation 134:175 asparagine-linked (N-linked) glycosylation 134:175 In the endoplasmic reticulum (ER), folding of proteins modified by asparagine-linked (N-linked) glycosylation is precisely monitored by quality control machinery. 24519966 8 39 theme hERManI 1334:1340 arg1 properties 1320:1329 The properties 1316:1329 The properties of hERManI 1316:1340 The properties of hERManI enable rapid selection of ERAD substrates in the ER and may help maintain homeostasis of sugar metabolism in living organisms. 24519966 3 40 theme α1,2-linked 487:497 arg1 residues 507:514 two or more α1,2-linked mannose residues 475:514 two or more α1,2-linked mannose residues 475:514 ERManI removes the α1,2-linked mannose of the B-chain from properly folded ER glycoproteins, whereas two or more α1,2-linked mannose residues are sequentially trimmed from improperly folded glycoproteins so they are recognized by a complex that mediates ER-associated degradation (ERAD). 24519966 3 41 theme mannose 499:505 arg1 residues 507:514 two or more α1,2-linked mannose residues 475:514 two or more α1,2-linked mannose residues 475:514 ERManI removes the α1,2-linked mannose of the B-chain from properly folded ER glycoproteins, whereas two or more α1,2-linked mannose residues are sequentially trimmed from improperly folded glycoproteins so they are recognized by a complex that mediates ER-associated degradation (ERAD). 24519966 0 42 theme human 38:42 arg1 I 64:64 human ER α1,2-mannosidase I 38:64 human ER α1,2-mannosidase I 38:64 Trimming of glucosylated N-glycans by human ER α1,2-mannosidase I. 24519966 7 43 theme immunoglobulin 1234:1247 arg1 IgY 1252:1254 chicken immunoglobulin Y (IgY) 1226:1255 chicken immunoglobulin Y (IgY) 1226:1255 The ability of hERManI to remove mannose residues from GlcMan9GlcNAc2 in model glycoproteins, such as Aspergillus oryzae β-galactosidase and chicken immunoglobulin Y (IgY), was markedly augmented when glycoproteins were denatured. 24519966 4 44 gly de-mannosylation 711:726 arg1 glycoproteins 737:749 model glycoproteins 731:749 model glycoproteins 731:749 We have shown that the efficiency of Man9GlcNAc2 de-mannosylation in model glycoproteins by recombinant human ERManI (hERManI) is dependent on folding status (Aikawa et al. (In vitro mannose trimming property of human ER α-1,2 mannosidase I. Glycoconj. 24519966 7 45 theme Y 1249:1249 arg1 IgY 1252:1254 chicken immunoglobulin Y (IgY) 1226:1255 chicken immunoglobulin Y (IgY) 1226:1255 The ability of hERManI to remove mannose residues from GlcMan9GlcNAc2 in model glycoproteins, such as Aspergillus oryzae β-galactosidase and chicken immunoglobulin Y (IgY), was markedly augmented when glycoproteins were denatured. 24519966 3 46 gly glycoproteins 452:464 arg1 glycoproteins 452:464 properly folded ER glycoproteins 433:464 properly folded ER glycoproteins 433:464 ERManI removes the α1,2-linked mannose of the B-chain from properly folded ER glycoproteins, whereas two or more α1,2-linked mannose residues are sequentially trimmed from improperly folded glycoproteins so they are recognized by a complex that mediates ER-associated degradation (ERAD). 24519966 7 47 gly glycoproteins 1286:1298 arg1 glycoproteins 1286:1298 glycoproteins 1286:1298 glycoproteins 1286:1298 The ability of hERManI to remove mannose residues from GlcMan9GlcNAc2 in model glycoproteins, such as Aspergillus oryzae β-galactosidase and chicken immunoglobulin Y (IgY), was markedly augmented when glycoproteins were denatured. 24519966 4 48 dep shown 670:674 arg1 Glycoconj 904:912 Glycoconj 904:912 Glycoconj 904:912 We have shown that the efficiency of Man9GlcNAc2 de-mannosylation in model glycoproteins by recombinant human ERManI (hERManI) is dependent on folding status (Aikawa et al. (In vitro mannose trimming property of human ER α-1,2 mannosidase I. Glycoconj. 24519966 3 49 theme ER-associated 628:640 arg1 ERAD 655:658 ERAD 655:658 ERAD 655:658 ERManI removes the α1,2-linked mannose of the B-chain from properly folded ER glycoproteins, whereas two or more α1,2-linked mannose residues are sequentially trimmed from improperly folded glycoproteins so they are recognized by a complex that mediates ER-associated degradation (ERAD). 24519966 3 49 theme ER-associated 628:640 arg1 degradation 642:652 ER-associated degradation 628:652 ER-associated degradation (ERAD) 628:659 ERManI removes the α1,2-linked mannose of the B-chain from properly folded ER glycoproteins, whereas two or more α1,2-linked mannose residues are sequentially trimmed from improperly folded glycoproteins so they are recognized by a complex that mediates ER-associated degradation (ERAD). 24519966 4 50 theme folding 805:811 arg1 status 813:818 folding status 805:818 folding status 805:818 We have shown that the efficiency of Man9GlcNAc2 de-mannosylation in model glycoproteins by recombinant human ERManI (hERManI) is dependent on folding status (Aikawa et al. (In vitro mannose trimming property of human ER α-1,2 mannosidase I. Glycoconj. 24519966 3 51 theme folded 442:447 arg1 glycoproteins 452:464 properly folded ER glycoproteins 433:464 properly folded ER glycoproteins 433:464 ERManI removes the α1,2-linked mannose of the B-chain from properly folded ER glycoproteins, whereas two or more α1,2-linked mannose residues are sequentially trimmed from improperly folded glycoproteins so they are recognized by a complex that mediates ER-associated degradation (ERAD). 24519966 0 52 theme α1,2-mannosidase 47:62 arg1 I 64:64 human ER α1,2-mannosidase I 38:64 human ER α1,2-mannosidase I 38:64 Trimming of glucosylated N-glycans by human ER α1,2-mannosidase I. 24519966 4 53 theme human 766:770 arg1 ERManI 772:777 recombinant human ERManI 754:777 recombinant human ERManI (hERManI) 754:787 We have shown that the efficiency of Man9GlcNAc2 de-mannosylation in model glycoproteins by recombinant human ERManI (hERManI) is dependent on folding status (Aikawa et al. (In vitro mannose trimming property of human ER α-1,2 mannosidase I. Glycoconj. 24519966 4 53 theme human 766:770 arg1 hERManI 780:786 hERManI 780:786 hERManI 780:786 We have shown that the efficiency of Man9GlcNAc2 de-mannosylation in model glycoproteins by recombinant human ERManI (hERManI) is dependent on folding status (Aikawa et al. (In vitro mannose trimming property of human ER α-1,2 mannosidase I. Glycoconj. 24519966 3 54 link α1,2-linked 393:403 arg1 mannose 405:411 the α1,2-linked mannose 389:411 the α1,2-linked mannose of the B-chain from properly folded ER glycoproteins 389:464 ERManI removes the α1,2-linked mannose of the B-chain from properly folded ER glycoproteins, whereas two or more α1,2-linked mannose residues are sequentially trimmed from improperly folded glycoproteins so they are recognized by a complex that mediates ER-associated degradation (ERAD). 24519966 4 55 theme Man9GlcNAc2 699:709 arg1 de-mannosylation 711:726 Man9GlcNAc2 de-mannosylation 699:726 Man9GlcNAc2 de-mannosylation in model glycoproteins 699:749 We have shown that the efficiency of Man9GlcNAc2 de-mannosylation in model glycoproteins by recombinant human ERManI (hERManI) is dependent on folding status (Aikawa et al. (In vitro mannose trimming property of human ER α-1,2 mannosidase I. Glycoconj. 24519966 0 56 theme ER 44:45 arg1 I 64:64 human ER α1,2-mannosidase I 38:64 human ER α1,2-mannosidase I 38:64 Trimming of glucosylated N-glycans by human ER α1,2-mannosidase I. 24519966 8 57 theme metabolism 1437:1446 arg1 homeostasis 1416:1426 homeostasis 1416:1426 homeostasis of sugar metabolism in living organisms 1416:1466 The properties of hERManI enable rapid selection of ERAD substrates in the ER and may help maintain homeostasis of sugar metabolism in living organisms. 24519966 8 58 theme rapid 1349:1353 arg1 selection 1355:1363 rapid selection 1349:1363 rapid selection of ERAD substrates in the ER 1349:1392 The properties of hERManI enable rapid selection of ERAD substrates in the ER and may help maintain homeostasis of sugar metabolism in living organisms. 24519966 7 59 theme chicken 1226:1232 arg1 IgY 1252:1254 chicken immunoglobulin Y (IgY) 1226:1255 chicken immunoglobulin Y (IgY) 1226:1255 The ability of hERManI to remove mannose residues from GlcMan9GlcNAc2 in model glycoproteins, such as Aspergillus oryzae β-galactosidase and chicken immunoglobulin Y (IgY), was markedly augmented when glycoproteins were denatured. 24519966 3 60 gly glycoproteins 564:576 arg1 glycoproteins 564:576 improperly folded glycoproteins 546:576 improperly folded glycoproteins so they are recognized by a complex that mediates ER-associated degradation (ERAD) 546:659 ERManI removes the α1,2-linked mannose of the B-chain from properly folded ER glycoproteins, whereas two or more α1,2-linked mannose residues are sequentially trimmed from improperly folded glycoproteins so they are recognized by a complex that mediates ER-associated degradation (ERAD). 24519966 2 61 from cycle 271:275 arg1 exit 235:238 exit 235:238 exit from the calnexin/calreticulin cycle 235:275 Upon exit from the calnexin/calreticulin cycle, glycoproteins are digested by α-mannosidases in the ER, especially α1,2-mannosidase I (ERManI). 24519966 8 62 theme substrates 1373:1382 arg1 selection 1355:1363 rapid selection 1349:1363 rapid selection of ERAD substrates in the ER 1349:1392 The properties of hERManI enable rapid selection of ERAD substrates in the ER and may help maintain homeostasis of sugar metabolism in living organisms. 24519966 4 63 theme ER 880:881 arg1 mannosidase 889:899 human ER α-1,2 mannosidase 874:899 human ER α-1,2 mannosidase 874:899 We have shown that the efficiency of Man9GlcNAc2 de-mannosylation in model glycoproteins by recombinant human ERManI (hERManI) is dependent on folding status (Aikawa et al. (In vitro mannose trimming property of human ER α-1,2 mannosidase I. Glycoconj. 24519966 8 64 theme ERAD 1368:1371 arg1 substrates 1373:1382 ERAD substrates 1368:1382 ERAD substrates 1368:1382 The properties of hERManI enable rapid selection of ERAD substrates in the ER and may help maintain homeostasis of sugar metabolism in living organisms. 24519966 3 65 from glycoproteins 452:464 arg1 B-chain 420:426 the B-chain 416:426 the B-chain from properly folded ER glycoproteins 416:464 ERManI removes the α1,2-linked mannose of the B-chain from properly folded ER glycoproteins, whereas two or more α1,2-linked mannose residues are sequentially trimmed from improperly folded glycoproteins so they are recognized by a complex that mediates ER-associated degradation (ERAD). 24519966 3 65 from glycoproteins 452:464 arg1 mannose 405:411 the α1,2-linked mannose 389:411 the α1,2-linked mannose of the B-chain from properly folded ER glycoproteins 389:464 ERManI removes the α1,2-linked mannose of the B-chain from properly folded ER glycoproteins, whereas two or more α1,2-linked mannose residues are sequentially trimmed from improperly folded glycoproteins so they are recognized by a complex that mediates ER-associated degradation (ERAD). 24519966 4 66 from de-mannosylation 711:726 arg1 glycoproteins 737:749 model glycoproteins 731:749 model glycoproteins 731:749 We have shown that the efficiency of Man9GlcNAc2 de-mannosylation in model glycoproteins by recombinant human ERManI (hERManI) is dependent on folding status (Aikawa et al. (In vitro mannose trimming property of human ER α-1,2 mannosidase I. Glycoconj. 24519966 1 67 theme quality 203:209 arg1 machinery 219:227 quality control machinery 203:227 quality control machinery 203:227 In the endoplasmic reticulum (ER), folding of proteins modified by asparagine-linked (N-linked) glycosylation is precisely monitored by quality control machinery. 24519966 4 68 theme human 874:878 arg1 mannosidase 889:899 human ER α-1,2 mannosidase 874:899 human ER α-1,2 mannosidase 874:899 We have shown that the efficiency of Man9GlcNAc2 de-mannosylation in model glycoproteins by recombinant human ERManI (hERManI) is dependent on folding status (Aikawa et al. (In vitro mannose trimming property of human ER α-1,2 mannosidase I. Glycoconj. 24519966 7 69 from GlcMan9GlcNAc2 1140:1153 arg1 IgY 1252:1254 chicken immunoglobulin Y (IgY) 1226:1255 chicken immunoglobulin Y (IgY) 1226:1255 The ability of hERManI to remove mannose residues from GlcMan9GlcNAc2 in model glycoproteins, such as Aspergillus oryzae β-galactosidase and chicken immunoglobulin Y (IgY), was markedly augmented when glycoproteins were denatured. 24519966 7 69 from GlcMan9GlcNAc2 1140:1153 arg1 glycoproteins 1164:1176 model glycoproteins 1158:1176 model glycoproteins 1158:1176 The ability of hERManI to remove mannose residues from GlcMan9GlcNAc2 in model glycoproteins, such as Aspergillus oryzae β-galactosidase and chicken immunoglobulin Y (IgY), was markedly augmented when glycoproteins were denatured. 24519966 7 69 from GlcMan9GlcNAc2 1140:1153 arg1 β-galactosidase 1206:1220 Aspergillus oryzae β-galactosidase 1187:1220 Aspergillus oryzae β-galactosidase 1187:1220 The ability of hERManI to remove mannose residues from GlcMan9GlcNAc2 in model glycoproteins, such as Aspergillus oryzae β-galactosidase and chicken immunoglobulin Y (IgY), was markedly augmented when glycoproteins were denatured. 24519966 8 70 theme sugar 1431:1435 arg1 metabolism 1437:1446 sugar metabolism 1431:1446 sugar metabolism 1431:1446 The properties of hERManI enable rapid selection of ERAD substrates in the ER and may help maintain homeostasis of sugar metabolism in living organisms. 24519966 4 71 theme de-mannosylation 711:726 arg1 dependent 792:800 dependent 792:800 dependent 792:800 We have shown that the efficiency of Man9GlcNAc2 de-mannosylation in model glycoproteins by recombinant human ERManI (hERManI) is dependent on folding status (Aikawa et al. (In vitro mannose trimming property of human ER α-1,2 mannosidase I. Glycoconj. 24519966 4 71 theme de-mannosylation 711:726 arg1 efficiency 685:694 the efficiency 681:694 the efficiency of Man9GlcNAc2 de-mannosylation in model glycoproteins by recombinant human ERManI (hERManI) 681:787 We have shown that the efficiency of Man9GlcNAc2 de-mannosylation in model glycoproteins by recombinant human ERManI (hERManI) is dependent on folding status (Aikawa et al. (In vitro mannose trimming property of human ER α-1,2 mannosidase I. Glycoconj. 24519966 4 71 theme de-mannosylation 711:726 arg1 Aikawa 821:826 Aikawa 821:826 Aikawa 821:826 We have shown that the efficiency of Man9GlcNAc2 de-mannosylation in model glycoproteins by recombinant human ERManI (hERManI) is dependent on folding status (Aikawa et al. (In vitro mannose trimming property of human ER α-1,2 mannosidase I. Glycoconj. 24519966 8 72 from homeostasis 1416:1426 arg1 organisms 1458:1466 living organisms 1451:1466 living organisms 1451:1466 The properties of hERManI enable rapid selection of ERAD substrates in the ER and may help maintain homeostasis of sugar metabolism in living organisms. 24519966 1 73 theme control 211:217 arg1 machinery 219:227 quality control machinery 203:227 quality control machinery 203:227 In the endoplasmic reticulum (ER), folding of proteins modified by asparagine-linked (N-linked) glycosylation is precisely monitored by quality control machinery. 24519966 4 74 dep Aikawa 821:826 arg1 al 831:832 Aikawa et al 821:832 Aikawa et al 821:832 We have shown that the efficiency of Man9GlcNAc2 de-mannosylation in model glycoproteins by recombinant human ERManI (hERManI) is dependent on folding status (Aikawa et al. (In vitro mannose trimming property of human ER α-1,2 mannosidase I. Glycoconj. 24519966 1 75 theme proteins 113:120 arg1 folding 102:108 folding 102:108 folding of proteins modified by asparagine-linked (N-linked) glycosylation 102:175 In the endoplasmic reticulum (ER), folding of proteins modified by asparagine-linked (N-linked) glycosylation is precisely monitored by quality control machinery. 24519966 4 76 dep dependent 792:800 arg1 dependent 792:800 dependent 792:800 dependent 792:800 We have shown that the efficiency of Man9GlcNAc2 de-mannosylation in model glycoproteins by recombinant human ERManI (hERManI) is dependent on folding status (Aikawa et al. (In vitro mannose trimming property of human ER α-1,2 mannosidase I. Glycoconj. 24519966 4 76 dep dependent 792:800 arg1 efficiency 685:694 the efficiency 681:694 the efficiency of Man9GlcNAc2 de-mannosylation in model glycoproteins by recombinant human ERManI (hERManI) 681:787 We have shown that the efficiency of Man9GlcNAc2 de-mannosylation in model glycoproteins by recombinant human ERManI (hERManI) is dependent on folding status (Aikawa et al. (In vitro mannose trimming property of human ER α-1,2 mannosidase I. Glycoconj. 24519966 4 76 dep dependent 792:800 arg1 Aikawa 821:826 Aikawa 821:826 Aikawa 821:826 We have shown that the efficiency of Man9GlcNAc2 de-mannosylation in model glycoproteins by recombinant human ERManI (hERManI) is dependent on folding status (Aikawa et al. (In vitro mannose trimming property of human ER α-1,2 mannosidase I. Glycoconj. 24519966 7 77 gly glycoproteins 1164:1176 arg1 IgY 1252:1254 chicken immunoglobulin Y (IgY) 1226:1255 chicken immunoglobulin Y (IgY) 1226:1255 The ability of hERManI to remove mannose residues from GlcMan9GlcNAc2 in model glycoproteins, such as Aspergillus oryzae β-galactosidase and chicken immunoglobulin Y (IgY), was markedly augmented when glycoproteins were denatured. 24519966 7 77 gly glycoproteins 1164:1176 arg1 glycoproteins 1164:1176 model glycoproteins 1158:1176 model glycoproteins 1158:1176 The ability of hERManI to remove mannose residues from GlcMan9GlcNAc2 in model glycoproteins, such as Aspergillus oryzae β-galactosidase and chicken immunoglobulin Y (IgY), was markedly augmented when glycoproteins were denatured. 24519966 7 77 gly glycoproteins 1164:1176 arg1 β-galactosidase 1206:1220 Aspergillus oryzae β-galactosidase 1187:1220 Aspergillus oryzae β-galactosidase 1187:1220 The ability of hERManI to remove mannose residues from GlcMan9GlcNAc2 in model glycoproteins, such as Aspergillus oryzae β-galactosidase and chicken immunoglobulin Y (IgY), was markedly augmented when glycoproteins were denatured. 24519966 6 78 link N-linked 993:1000 arg1 substrates 1040:1049 substrates 1040:1049 substrates with nearly identical reactivity 1040:1082 In this study, we revealed that this enzyme also accepts N-linked sugar chains with glucose moieties as substrates with nearly identical reactivity. 24519966 6 78 link N-linked 993:1000 arg1 chains 1008:1013 N-linked sugar chains 993:1013 N-linked sugar chains 993:1013 In this study, we revealed that this enzyme also accepts N-linked sugar chains with glucose moieties as substrates with nearly identical reactivity. 24519966 7 79 theme hERManI 1100:1106 arg1 ability 1089:1095 The ability 1085:1095 The ability of hERManI to remove mannose residues from GlcMan9GlcNAc2 in model glycoproteins, such as Aspergillus oryzae β-galactosidase and chicken immunoglobulin Y (IgY), 1085:1256 The ability of hERManI to remove mannose residues from GlcMan9GlcNAc2 in model glycoproteins, such as Aspergillus oryzae β-galactosidase and chicken immunoglobulin Y (IgY), was markedly augmented when glycoproteins were denatured. 24519966 7 80 theme oryzae 1199:1204 arg1 β-galactosidase 1206:1220 Aspergillus oryzae β-galactosidase 1187:1220 Aspergillus oryzae β-galactosidase 1187:1220 The ability of hERManI to remove mannose residues from GlcMan9GlcNAc2 in model glycoproteins, such as Aspergillus oryzae β-galactosidase and chicken immunoglobulin Y (IgY), was markedly augmented when glycoproteins were denatured. 24519966 4 81 from efficiency 685:694 arg1 glycoproteins 737:749 model glycoproteins 731:749 model glycoproteins 731:749 We have shown that the efficiency of Man9GlcNAc2 de-mannosylation in model glycoproteins by recombinant human ERManI (hERManI) is dependent on folding status (Aikawa et al. (In vitro mannose trimming property of human ER α-1,2 mannosidase I. Glycoconj. 24519966 4 82 gly glycoproteins 737:749 arg1 glycoproteins 737:749 model glycoproteins 731:749 model glycoproteins 731:749 We have shown that the efficiency of Man9GlcNAc2 de-mannosylation in model glycoproteins by recombinant human ERManI (hERManI) is dependent on folding status (Aikawa et al. (In vitro mannose trimming property of human ER α-1,2 mannosidase I. Glycoconj. 26673325 4 0 theme mass 678:681 arg1 loss 663:666 the loss 659:666 the loss of β cell mass due to ER-stress-induced apoptosis 659:716 βOGT-KO mice demonstrated increased ER stress and distended ER architecture, and these changes ultimately caused the loss of β cell mass due to ER-stress-induced apoptosis and decreased proliferation. 26673325 0 1 theme Cell 77:80 arg1 Failure 82:88 Cell Failure 77:88 Cell Failure 77:88 Disruption of O-linked N-Acetylglucosamine Signaling Induces ER Stress and β Cell Failure. 26673325 6 2 theme gene 922:925 arg1 deletion 927:934 concomitant Chop gene deletion 905:934 concomitant Chop gene deletion 905:934 The mechanistic role of these processes was demonstrated by rescuing the phenotype of βOGT-KO mice with concomitant Chop gene deletion or genetic reconstitution of Akt2. 26673325 7 3 theme direct 1056:1061 arg1 link 1063:1066 a direct link 1054:1066 a direct link between O-GlcNAcylation and β cell survival 1054:1110 These findings identify OGT as a regulator of β cell mass and function and provide a direct link between O-GlcNAcylation and β cell survival by regulation of ER stress responses and modulation of Akt1/2 signaling. 26673325 1 4 theme intracellular 266:278 arg1 signaling 280:288 intracellular signaling 266:288 intracellular signaling 266:288 Nutrient levels dictate the activity of O-linked N-acetylglucosamine transferase (OGT) to regulate O-GlcNAcylation, a post-translational modification mechanism to "fine-tune" intracellular signaling and metabolic status. 26673325 5 5 from islets 793:798 arg1 dampened 773:780 dampened 773:780 dampened 773:780 Akt1/2 signaling was also dampened in βOGT-KO islets. 26673325 0 6 link O-linked 14:21 arg1 N-Acetylglucosamine 23:41 O-linked N-Acetylglucosamine 14:41 O-linked N-Acetylglucosamine Signaling 14:51 Disruption of O-linked N-Acetylglucosamine Signaling Induces ER Stress and β Cell Failure. 26673325 4 7 theme distended 596:604 arg1 architecture 609:620 distended ER architecture 596:620 distended ER architecture 596:620 βOGT-KO mice demonstrated increased ER stress and distended ER architecture, and these changes ultimately caused the loss of β cell mass due to ER-stress-induced apoptosis and decreased proliferation. 26673325 6 8 theme concomitant 905:915 arg1 deletion 927:934 concomitant Chop gene deletion 905:934 concomitant Chop gene deletion 905:934 The mechanistic role of these processes was demonstrated by rescuing the phenotype of βOGT-KO mice with concomitant Chop gene deletion or genetic reconstitution of Akt2. 26673325 7 9 theme responses 1139:1147 arg1 regulation 1115:1124 regulation 1115:1124 regulation of ER stress responses 1115:1147 These findings identify OGT as a regulator of β cell mass and function and provide a direct link between O-GlcNAcylation and β cell survival by regulation of ER stress responses and modulation of Akt1/2 signaling. 26673325 7 9 theme responses 1139:1147 arg1 modulation 1153:1162 modulation 1153:1162 modulation of Akt1/2 signaling 1153:1182 These findings identify OGT as a regulator of β cell mass and function and provide a direct link between O-GlcNAcylation and β cell survival by regulation of ER stress responses and modulation of Akt1/2 signaling. 26673325 1 10 theme O-linked 131:138 arg1 transferase 160:170 O-linked N-acetylglucosamine transferase 131:170 O-linked N-acetylglucosamine transferase (OGT) 131:176 Nutrient levels dictate the activity of O-linked N-acetylglucosamine transferase (OGT) to regulate O-GlcNAcylation, a post-translational modification mechanism to "fine-tune" intracellular signaling and metabolic status. 26673325 1 10 theme O-linked 131:138 arg1 OGT 173:175 OGT 173:175 OGT 173:175 Nutrient levels dictate the activity of O-linked N-acetylglucosamine transferase (OGT) to regulate O-GlcNAcylation, a post-translational modification mechanism to "fine-tune" intracellular signaling and metabolic status. 26673325 5 11 theme Akt1/2 747:752 arg1 signaling 754:762 Akt1/2 signaling 747:762 Akt1/2 signaling 747:762 Akt1/2 signaling was also dampened in βOGT-KO islets. 26673325 3 12 theme β 488:488 arg1 βOGT-KO 500:506 βOGT-KO 500:506 βOGT-KO 500:506 Here, we reveal that mice lacking β cell OGT (βOGT-KO) develop diabetes and β cell failure. 26673325 3 12 theme β 488:488 arg1 OGT 495:497 β cell OGT 488:497 β cell OGT (βOGT-KO) 488:507 Here, we reveal that mice lacking β cell OGT (βOGT-KO) develop diabetes and β cell failure. 26673325 3 13 theme β 530:530 arg1 failure 537:543 β cell failure 530:543 β cell failure 530:543 Here, we reveal that mice lacking β cell OGT (βOGT-KO) develop diabetes and β cell failure. 26673325 7 14 theme stress 1132:1137 arg1 responses 1139:1147 ER stress responses 1129:1147 ER stress responses 1129:1147 These findings identify OGT as a regulator of β cell mass and function and provide a direct link between O-GlcNAcylation and β cell survival by regulation of ER stress responses and modulation of Akt1/2 signaling. 26673325 6 15 theme mice 895:898 arg1 phenotype 874:882 the phenotype 870:882 the phenotype of βOGT-KO mice 870:898 The mechanistic role of these processes was demonstrated by rescuing the phenotype of βOGT-KO mice with concomitant Chop gene deletion or genetic reconstitution of Akt2. 26673325 7 16 theme cell 1098:1101 arg1 survival 1103:1110 cell survival 1098:1110 cell survival 1098:1110 These findings identify OGT as a regulator of β cell mass and function and provide a direct link between O-GlcNAcylation and β cell survival by regulation of ER stress responses and modulation of Akt1/2 signaling. 26673325 3 17 theme cell 532:535 arg1 failure 537:543 β cell failure 530:543 β cell failure 530:543 Here, we reveal that mice lacking β cell OGT (βOGT-KO) develop diabetes and β cell failure. 26673325 7 18 theme Akt1/2 1167:1172 arg1 signaling 1174:1182 Akt1/2 signaling 1167:1182 Akt1/2 signaling 1167:1182 These findings identify OGT as a regulator of β cell mass and function and provide a direct link between O-GlcNAcylation and β cell survival by regulation of ER stress responses and modulation of Akt1/2 signaling. 26673325 6 19 theme βOGT-KO 887:893 arg1 mice 895:898 βOGT-KO mice 887:898 βOGT-KO mice 887:898 The mechanistic role of these processes was demonstrated by rescuing the phenotype of βOGT-KO mice with concomitant Chop gene deletion or genetic reconstitution of Akt2. 26673325 4 20 theme β 671:671 arg1 mass 678:681 β cell mass 671:681 β cell mass 671:681 βOGT-KO mice demonstrated increased ER stress and distended ER architecture, and these changes ultimately caused the loss of β cell mass due to ER-stress-induced apoptosis and decreased proliferation. 26673325 7 21 theme signaling 1174:1182 arg1 regulation 1115:1124 regulation 1115:1124 regulation of ER stress responses 1115:1147 These findings identify OGT as a regulator of β cell mass and function and provide a direct link between O-GlcNAcylation and β cell survival by regulation of ER stress responses and modulation of Akt1/2 signaling. 26673325 7 21 theme signaling 1174:1182 arg1 modulation 1153:1162 modulation 1153:1162 modulation of Akt1/2 signaling 1153:1182 These findings identify OGT as a regulator of β cell mass and function and provide a direct link between O-GlcNAcylation and β cell survival by regulation of ER stress responses and modulation of Akt1/2 signaling. 26673325 1 22 theme metabolic 294:302 arg1 status 304:309 metabolic status 294:309 metabolic status 294:309 Nutrient levels dictate the activity of O-linked N-acetylglucosamine transferase (OGT) to regulate O-GlcNAcylation, a post-translational modification mechanism to "fine-tune" intracellular signaling and metabolic status. 26673325 1 23 theme Nutrient 91:98 arg1 levels 100:105 Nutrient levels 91:105 Nutrient levels 91:105 Nutrient levels dictate the activity of O-linked N-acetylglucosamine transferase (OGT) to regulate O-GlcNAcylation, a post-translational modification mechanism to "fine-tune" intracellular signaling and metabolic status. 26673325 2 24 theme β 417:417 arg1 cell 419:422 pancreatic β cell mass and function 406:440 pancreatic β cell mass and function 406:440 However, the requirement of O-GlcNAcylation for maintaining glucose homeostasis by regulating pancreatic β cell mass and function is unclear. 26673325 0 25 theme N-Acetylglucosamine 23:41 arg1 Signaling 43:51 O-linked N-Acetylglucosamine Signaling 14:51 O-linked N-Acetylglucosamine Signaling 14:51 Disruption of O-linked N-Acetylglucosamine Signaling Induces ER Stress and β Cell Failure. 26673325 4 26 theme βOGT-KO 546:552 arg1 mice 554:557 βOGT-KO mice 546:557 βOGT-KO mice 546:557 βOGT-KO mice demonstrated increased ER stress and distended ER architecture, and these changes ultimately caused the loss of β cell mass due to ER-stress-induced apoptosis and decreased proliferation. 26673325 6 27 theme mechanistic 805:815 arg1 role 817:820 The mechanistic role 801:820 The mechanistic role of these processes 801:839 The mechanistic role of these processes was demonstrated by rescuing the phenotype of βOGT-KO mice with concomitant Chop gene deletion or genetic reconstitution of Akt2. 26673325 0 28 theme O-linked 14:21 arg1 N-Acetylglucosamine 23:41 O-linked N-Acetylglucosamine 14:41 O-linked N-Acetylglucosamine Signaling 14:51 Disruption of O-linked N-Acetylglucosamine Signaling Induces ER Stress and β Cell Failure. 26673325 4 29 theme increased 572:580 arg1 stress 585:590 increased ER stress 572:590 increased ER stress 572:590 βOGT-KO mice demonstrated increased ER stress and distended ER architecture, and these changes ultimately caused the loss of β cell mass due to ER-stress-induced apoptosis and decreased proliferation. 26673325 7 30 theme β 1017:1017 arg1 mass 1024:1027 β cell mass 1017:1027 β cell mass 1017:1027 These findings identify OGT as a regulator of β cell mass and function and provide a direct link between O-GlcNAcylation and β cell survival by regulation of ER stress responses and modulation of Akt1/2 signaling. 26673325 1 31 theme N-acetylglucosamine 140:158 arg1 transferase 160:170 O-linked N-acetylglucosamine transferase 131:170 O-linked N-acetylglucosamine transferase (OGT) 131:176 Nutrient levels dictate the activity of O-linked N-acetylglucosamine transferase (OGT) to regulate O-GlcNAcylation, a post-translational modification mechanism to "fine-tune" intracellular signaling and metabolic status. 26673325 1 31 theme N-acetylglucosamine 140:158 arg1 OGT 173:175 OGT 173:175 OGT 173:175 Nutrient levels dictate the activity of O-linked N-acetylglucosamine transferase (OGT) to regulate O-GlcNAcylation, a post-translational modification mechanism to "fine-tune" intracellular signaling and metabolic status. 26673325 5 32 theme βOGT-KO 785:791 arg1 islets 793:798 βOGT-KO islets 785:798 βOGT-KO islets 785:798 Akt1/2 signaling was also dampened in βOGT-KO islets. 26673325 1 33 theme post-translational 209:226 arg1 O-GlcNAcylation 190:204 O-GlcNAcylation 190:204 O-GlcNAcylation 190:204 Nutrient levels dictate the activity of O-linked N-acetylglucosamine transferase (OGT) to regulate O-GlcNAcylation, a post-translational modification mechanism to "fine-tune" intracellular signaling and metabolic status. 26673325 1 33 theme post-translational 209:226 arg1 modification 228:239 a post-translational modification 207:239 a post-translational modification mechanism to "fine-tune" intracellular signaling and metabolic status 207:309 Nutrient levels dictate the activity of O-linked N-acetylglucosamine transferase (OGT) to regulate O-GlcNAcylation, a post-translational modification mechanism to "fine-tune" intracellular signaling and metabolic status. 26673325 0 34 theme Signaling 43:51 arg1 Disruption 0:9 Disruption 0:9 Disruption of O-linked N-Acetylglucosamine Signaling 0:51 Disruption of O-linked N-Acetylglucosamine Signaling Induces ER Stress and β Cell Failure. 26673325 6 35 theme Akt2 965:968 arg1 deletion 927:934 concomitant Chop gene deletion 905:934 concomitant Chop gene deletion 905:934 The mechanistic role of these processes was demonstrated by rescuing the phenotype of βOGT-KO mice with concomitant Chop gene deletion or genetic reconstitution of Akt2. 26673325 6 35 theme Akt2 965:968 arg1 reconstitution 947:960 genetic reconstitution 939:960 genetic reconstitution of Akt2 939:968 The mechanistic role of these processes was demonstrated by rescuing the phenotype of βOGT-KO mice with concomitant Chop gene deletion or genetic reconstitution of Akt2. 26673325 4 36 theme ER 582:583 arg1 stress 585:590 increased ER stress 572:590 increased ER stress 572:590 βOGT-KO mice demonstrated increased ER stress and distended ER architecture, and these changes ultimately caused the loss of β cell mass due to ER-stress-induced apoptosis and decreased proliferation. 26673325 7 37 theme cell 1019:1022 arg1 mass 1024:1027 β cell mass 1017:1027 β cell mass 1017:1027 These findings identify OGT as a regulator of β cell mass and function and provide a direct link between O-GlcNAcylation and β cell survival by regulation of ER stress responses and modulation of Akt1/2 signaling. 26673325 7 38 theme ER 1129:1130 arg1 responses 1139:1147 ER stress responses 1129:1147 ER stress responses 1129:1147 These findings identify OGT as a regulator of β cell mass and function and provide a direct link between O-GlcNAcylation and β cell survival by regulation of ER stress responses and modulation of Akt1/2 signaling. 26673325 7 39 theme mass 1024:1027 arg1 OGT 995:997 OGT 995:997 OGT 995:997 These findings identify OGT as a regulator of β cell mass and function and provide a direct link between O-GlcNAcylation and β cell survival by regulation of ER stress responses and modulation of Akt1/2 signaling. 26673325 7 39 theme mass 1024:1027 arg1 regulator 1004:1012 a regulator 1002:1012 a regulator of β cell mass and function 1002:1040 These findings identify OGT as a regulator of β cell mass and function and provide a direct link between O-GlcNAcylation and β cell survival by regulation of ER stress responses and modulation of Akt1/2 signaling. 26673325 2 40 theme glucose 372:378 arg1 homeostasis 380:390 glucose homeostasis 372:390 glucose homeostasis 372:390 However, the requirement of O-GlcNAcylation for maintaining glucose homeostasis by regulating pancreatic β cell mass and function is unclear. 26673325 0 41 theme ER 61:62 arg1 Stress 64:69 ER Stress 61:69 ER Stress 61:69 Disruption of O-linked N-Acetylglucosamine Signaling Induces ER Stress and β Cell Failure. 26673325 1 42 link O-linked 131:138 arg1 transferase 160:170 O-linked N-acetylglucosamine transferase 131:170 O-linked N-acetylglucosamine transferase (OGT) 131:176 Nutrient levels dictate the activity of O-linked N-acetylglucosamine transferase (OGT) to regulate O-GlcNAcylation, a post-translational modification mechanism to "fine-tune" intracellular signaling and metabolic status. 26673325 1 42 link O-linked 131:138 arg1 OGT 173:175 OGT 173:175 OGT 173:175 Nutrient levels dictate the activity of O-linked N-acetylglucosamine transferase (OGT) to regulate O-GlcNAcylation, a post-translational modification mechanism to "fine-tune" intracellular signaling and metabolic status. 26673325 5 43 from dampened 773:780 arg1 islets 793:798 βOGT-KO islets 785:798 βOGT-KO islets 785:798 Akt1/2 signaling was also dampened in βOGT-KO islets. 26673325 4 44 theme ER-stress-induced 690:706 arg1 apoptosis 708:716 ER-stress-induced apoptosis 690:716 ER-stress-induced apoptosis 690:716 βOGT-KO mice demonstrated increased ER stress and distended ER architecture, and these changes ultimately caused the loss of β cell mass due to ER-stress-induced apoptosis and decreased proliferation. 26673325 6 45 theme genetic 939:945 arg1 reconstitution 947:960 genetic reconstitution 939:960 genetic reconstitution of Akt2 939:968 The mechanistic role of these processes was demonstrated by rescuing the phenotype of βOGT-KO mice with concomitant Chop gene deletion or genetic reconstitution of Akt2. 26673325 2 46 dep cell 419:422 arg1 mass 424:427 mass 424:427 mass 424:427 However, the requirement of O-GlcNAcylation for maintaining glucose homeostasis by regulating pancreatic β cell mass and function is unclear. 26673325 2 46 dep cell 419:422 arg1 function 433:440 function 433:440 function 433:440 However, the requirement of O-GlcNAcylation for maintaining glucose homeostasis by regulating pancreatic β cell mass and function is unclear. 26673325 4 47 theme cell 673:676 arg1 mass 678:681 β cell mass 671:681 β cell mass 671:681 βOGT-KO mice demonstrated increased ER stress and distended ER architecture, and these changes ultimately caused the loss of β cell mass due to ER-stress-induced apoptosis and decreased proliferation. 26673325 3 48 theme cell 490:493 arg1 βOGT-KO 500:506 βOGT-KO 500:506 βOGT-KO 500:506 Here, we reveal that mice lacking β cell OGT (βOGT-KO) develop diabetes and β cell failure. 26673325 3 48 theme cell 490:493 arg1 OGT 495:497 β cell OGT 488:497 β cell OGT (βOGT-KO) 488:507 Here, we reveal that mice lacking β cell OGT (βOGT-KO) develop diabetes and β cell failure. 26673325 7 49 theme function 1033:1040 arg1 OGT 995:997 OGT 995:997 OGT 995:997 These findings identify OGT as a regulator of β cell mass and function and provide a direct link between O-GlcNAcylation and β cell survival by regulation of ER stress responses and modulation of Akt1/2 signaling. 26673325 7 49 theme function 1033:1040 arg1 regulator 1004:1012 a regulator 1002:1012 a regulator of β cell mass and function 1002:1040 These findings identify OGT as a regulator of β cell mass and function and provide a direct link between O-GlcNAcylation and β cell survival by regulation of ER stress responses and modulation of Akt1/2 signaling. 26673325 1 50 dep " 264:264 arg1 signaling 280:288 intracellular signaling 266:288 intracellular signaling 266:288 Nutrient levels dictate the activity of O-linked N-acetylglucosamine transferase (OGT) to regulate O-GlcNAcylation, a post-translational modification mechanism to "fine-tune" intracellular signaling and metabolic status. 26673325 1 51 dep modification 228:239 arg1 mechanism 241:249 mechanism 241:249 mechanism 241:249 Nutrient levels dictate the activity of O-linked N-acetylglucosamine transferase (OGT) to regulate O-GlcNAcylation, a post-translational modification mechanism to "fine-tune" intracellular signaling and metabolic status. 26673325 2 52 theme O-GlcNAcylation 340:354 arg1 unclear 445:451 unclear 445:451 unclear 445:451 However, the requirement of O-GlcNAcylation for maintaining glucose homeostasis by regulating pancreatic β cell mass and function is unclear. 26673325 2 52 theme O-GlcNAcylation 340:354 arg1 requirement 325:335 the requirement 321:335 the requirement of O-GlcNAcylation for maintaining glucose homeostasis by regulating pancreatic β cell mass and function 321:440 However, the requirement of O-GlcNAcylation for maintaining glucose homeostasis by regulating pancreatic β cell mass and function is unclear. 26673325 4 53 theme ER 606:607 arg1 architecture 609:620 distended ER architecture 596:620 distended ER architecture 596:620 βOGT-KO mice demonstrated increased ER stress and distended ER architecture, and these changes ultimately caused the loss of β cell mass due to ER-stress-induced apoptosis and decreased proliferation. 26673325 6 54 theme processes 831:839 arg1 role 817:820 The mechanistic role 801:820 The mechanistic role of these processes 801:839 The mechanistic role of these processes was demonstrated by rescuing the phenotype of βOGT-KO mice with concomitant Chop gene deletion or genetic reconstitution of Akt2. 26673325 7 55 dep O-GlcNAcylation 1076:1090 arg1 survival 1103:1110 cell survival 1098:1110 cell survival 1098:1110 These findings identify OGT as a regulator of β cell mass and function and provide a direct link between O-GlcNAcylation and β cell survival by regulation of ER stress responses and modulation of Akt1/2 signaling. 26673325 2 56 theme pancreatic 406:415 arg1 cell 419:422 pancreatic β cell mass and function 406:440 pancreatic β cell mass and function 406:440 However, the requirement of O-GlcNAcylation for maintaining glucose homeostasis by regulating pancreatic β cell mass and function is unclear. 26673325 6 57 theme Chop 917:920 arg1 deletion 927:934 concomitant Chop gene deletion 905:934 concomitant Chop gene deletion 905:934 The mechanistic role of these processes was demonstrated by rescuing the phenotype of βOGT-KO mice with concomitant Chop gene deletion or genetic reconstitution of Akt2. 26673325 1 58 theme transferase 160:170 arg1 activity 119:126 the activity 115:126 the activity of O-linked N-acetylglucosamine transferase (OGT) to regulate O-GlcNAcylation, a post-translational modification mechanism to "fine-tune" intracellular signaling and metabolic status 115:309 Nutrient levels dictate the activity of O-linked N-acetylglucosamine transferase (OGT) to regulate O-GlcNAcylation, a post-translational modification mechanism to "fine-tune" intracellular signaling and metabolic status. 26673325 1 59 theme fine-tune 255:263 arg1 " 264:264 "fine-tune" 254:264 "fine-tune" 254:264 Nutrient levels dictate the activity of O-linked N-acetylglucosamine transferase (OGT) to regulate O-GlcNAcylation, a post-translational modification mechanism to "fine-tune" intracellular signaling and metabolic status. 27497430 6 0 theme glycosylation 1216:1228 arg1 terms 1154:1158 terms 1154:1158 terms of aggregates, fragments, charge isoforms, and N-linked glycosylation 1154:1228 Stable operation was achieved at three consecutive viable cell density set points (20, 60, and 40 × 106 cells/mL), together with consistent product quality in terms of aggregates, fragments, charge isoforms, and N-linked glycosylation. 27497430 9 1 theme product 1614:1620 arg1 control 1630:1636 product quality control 1614:1636 product quality control 1614:1636 This study is exemplary for the potential of enhancing product quality control and modulation by integrated continuous manufacturing. 27497430 1 2 theme biopharmaceutical 169:185 arg1 industry 187:194 the biopharmaceutical industry 165:194 the biopharmaceutical industry 165:194 Continuous manufacturing is currently being seriously considered in the biopharmaceutical industry as the possible new paradigm for producing therapeutic proteins, due to production cost and product quality related benefits. 27497430 1 3 theme production 268:277 arg1 cost 279:282 production cost 268:282 production cost 268:282 Continuous manufacturing is currently being seriously considered in the biopharmaceutical industry as the possible new paradigm for producing therapeutic proteins, due to production cost and product quality related benefits. 27497430 0 4 theme production 77:86 arg1 process 88:94 an integrated continuous antibody production process 43:94 an integrated continuous antibody production process 43:94 Process performance and product quality in an integrated continuous antibody production process. 27497430 9 5 theme quality 1622:1628 arg1 control 1630:1636 product quality control 1614:1636 product quality control 1614:1636 This study is exemplary for the potential of enhancing product quality control and modulation by integrated continuous manufacturing. 27497430 8 6 theme upstream 1528:1535 arg1 conditions 1547:1556 all considered upstream operating conditions 1513:1556 all considered upstream operating conditions 1513:1556 As expected, the amount of released DNA and HCP was significantly reduced by the capture step for all considered upstream operating conditions. 27497430 2 7 theme CHO 369:371 arg1 line 378:381 CHO cell line 369:381 CHO cell line 369:381 In this study, a monoclonal antibody producing CHO cell line was cultured in perfusion mode and connected to a continuous affinity capture step. 27497430 9 8 theme integrated 1656:1665 arg1 manufacturing 1678:1690 integrated continuous manufacturing 1656:1690 integrated continuous manufacturing 1656:1690 This study is exemplary for the potential of enhancing product quality control and modulation by integrated continuous manufacturing. 27497430 13 9 dep © 1732:1732 arg1 Inc. 1758:1761 Inc. 1758:1761 Inc. 1758:1761 © 2016 Wiley Periodicals, Inc. 27497430 3 10 theme control 546:552 arg1 loops 554:558 suitable control loops 537:558 suitable control loops 537:558 The reliable and stable integration of the two systems was enabled by suitable control loops, regulating the continuous volumetric flow and adapting the operating conditions of the capture process. 27497430 5 11 theme target 974:979 arg1 value 981:985 the target value 970:985 the target value of 99% 970:992 Thereby, optimal buffer consumption and productivity throughout the process was realized while always maintaining a yield above the target value of 99%. 27497430 6 12 theme Stable 995:1000 arg1 operation 1002:1010 Stable operation 995:1010 Stable operation 995:1010 Stable operation was achieved at three consecutive viable cell density set points (20, 60, and 40 × 106 cells/mL), together with consistent product quality in terms of aggregates, fragments, charge isoforms, and N-linked glycosylation. 27497430 6 13 theme product 1135:1141 arg1 quality 1143:1149 consistent product quality 1124:1149 consistent product quality in terms of aggregates, fragments, charge isoforms, and N-linked glycosylation 1124:1228 Stable operation was achieved at three consecutive viable cell density set points (20, 60, and 40 × 106 cells/mL), together with consistent product quality in terms of aggregates, fragments, charge isoforms, and N-linked glycosylation. 27497430 2 14 theme cell 373:376 arg1 line 378:381 CHO cell line 369:381 CHO cell line 369:381 In this study, a monoclonal antibody producing CHO cell line was cultured in perfusion mode and connected to a continuous affinity capture step. 27497430 1 15 theme product 288:294 arg1 benefits 312:319 product quality related benefits 288:319 product quality related benefits 288:319 Continuous manufacturing is currently being seriously considered in the biopharmaceutical industry as the possible new paradigm for producing therapeutic proteins, due to production cost and product quality related benefits. 27497430 4 16 theme HPLC 692:695 arg1 measurement 697:707 an at-line HPLC measurement 681:707 an at-line HPLC measurement of the harvest concentration subsequent to the bioreactor 681:765 For the latter, an at-line HPLC measurement of the harvest concentration subsequent to the bioreactor was combined with a mechanistic model of the capture chromatographic unit. 27497430 4 17 theme subsequent 738:747 arg1 concentration 724:736 the harvest concentration 712:736 the harvest concentration subsequent to the bioreactor 712:765 For the latter, an at-line HPLC measurement of the harvest concentration subsequent to the bioreactor was combined with a mechanistic model of the capture chromatographic unit. 27497430 7 18 theme different 1390:1398 arg1 states 1407:1412 the different steady states 1386:1412 the different steady states 1386:1412 In addition, different values for these product quality attributes such as N-linked glycosylation, charge variants, and aggregate content were measured at the different steady states. 27497430 7 19 theme steady 1400:1405 arg1 states 1407:1412 the different steady states 1386:1412 the different steady states 1386:1412 In addition, different values for these product quality attributes such as N-linked glycosylation, charge variants, and aggregate content were measured at the different steady states. 27497430 7 20 theme N-linked 1306:1313 arg1 glycosylation 1315:1327 N-linked glycosylation 1306:1327 N-linked glycosylation 1306:1327 In addition, different values for these product quality attributes such as N-linked glycosylation, charge variants, and aggregate content were measured at the different steady states. 27497430 8 21 theme DNA 1451:1453 arg1 HCP 1459:1461 HCP 1459:1461 HCP 1459:1461 As expected, the amount of released DNA and HCP was significantly reduced by the capture step for all considered upstream operating conditions. 27497430 8 21 theme DNA 1451:1453 arg1 amount 1432:1437 the amount 1428:1437 the amount of released DNA 1428:1453 As expected, the amount of released DNA and HCP was significantly reduced by the capture step for all considered upstream operating conditions. 27497430 8 21 theme DNA 1451:1453 arg1 DNA 1451:1453 released DNA 1442:1453 released DNA 1442:1453 As expected, the amount of released DNA and HCP was significantly reduced by the capture step for all considered upstream operating conditions. 27497430 3 22 theme suitable 537:544 arg1 loops 554:558 suitable control loops 537:558 suitable control loops 537:558 The reliable and stable integration of the two systems was enabled by suitable control loops, regulating the continuous volumetric flow and adapting the operating conditions of the capture process. 27497430 2 23 theme perfusion 399:407 arg1 mode 409:412 perfusion mode 399:412 perfusion mode 399:412 In this study, a monoclonal antibody producing CHO cell line was cultured in perfusion mode and connected to a continuous affinity capture step. 27497430 8 24 theme capture 1496:1502 arg1 step 1504:1507 the capture step 1492:1507 the capture step for all considered upstream operating conditions 1492:1556 As expected, the amount of released DNA and HCP was significantly reduced by the capture step for all considered upstream operating conditions. 27497430 7 25 link N-linked 1306:1313 arg1 glycosylation 1315:1327 N-linked glycosylation 1306:1327 N-linked glycosylation 1306:1327 In addition, different values for these product quality attributes such as N-linked glycosylation, charge variants, and aggregate content were measured at the different steady states. 27497430 7 26 theme different 1244:1252 arg1 values 1254:1259 different values 1244:1259 different values for these product quality attributes such as N-linked glycosylation, charge variants, and aggregate content 1244:1367 In addition, different values for these product quality attributes such as N-linked glycosylation, charge variants, and aggregate content were measured at the different steady states. 27497430 1 27 theme possible 203:210 arg1 manufacturing 108:120 Continuous manufacturing 97:120 Continuous manufacturing 97:120 Continuous manufacturing is currently being seriously considered in the biopharmaceutical industry as the possible new paradigm for producing therapeutic proteins, due to production cost and product quality related benefits. 27497430 1 27 theme possible 203:210 arg1 paradigm 216:223 the possible new paradigm 199:223 the possible new paradigm for producing therapeutic proteins, due to production cost and product quality related benefits 199:319 Continuous manufacturing is currently being seriously considered in the biopharmaceutical industry as the possible new paradigm for producing therapeutic proteins, due to production cost and product quality related benefits. 27497430 2 28 theme capture 453:459 arg1 step 461:464 a continuous affinity capture step 431:464 a continuous affinity capture step 431:464 In this study, a monoclonal antibody producing CHO cell line was cultured in perfusion mode and connected to a continuous affinity capture step. 27497430 1 29 theme quality 296:302 arg1 benefits 312:319 product quality related benefits 288:319 product quality related benefits 288:319 Continuous manufacturing is currently being seriously considered in the biopharmaceutical industry as the possible new paradigm for producing therapeutic proteins, due to production cost and product quality related benefits. 27497430 4 30 theme harvest 716:722 arg1 concentration 724:736 the harvest concentration 712:736 the harvest concentration subsequent to the bioreactor 712:765 For the latter, an at-line HPLC measurement of the harvest concentration subsequent to the bioreactor was combined with a mechanistic model of the capture chromatographic unit. 27497430 1 31 theme Continuous 97:106 arg1 manufacturing 108:120 Continuous manufacturing 97:120 Continuous manufacturing 97:120 Continuous manufacturing is currently being seriously considered in the biopharmaceutical industry as the possible new paradigm for producing therapeutic proteins, due to production cost and product quality related benefits. 27497430 1 31 theme Continuous 97:106 arg1 paradigm 216:223 the possible new paradigm 199:223 the possible new paradigm for producing therapeutic proteins, due to production cost and product quality related benefits 199:319 Continuous manufacturing is currently being seriously considered in the biopharmaceutical industry as the possible new paradigm for producing therapeutic proteins, due to production cost and product quality related benefits. 27497430 1 32 theme new 212:214 arg1 manufacturing 108:120 Continuous manufacturing 97:120 Continuous manufacturing 97:120 Continuous manufacturing is currently being seriously considered in the biopharmaceutical industry as the possible new paradigm for producing therapeutic proteins, due to production cost and product quality related benefits. 27497430 1 32 theme new 212:214 arg1 paradigm 216:223 the possible new paradigm 199:223 the possible new paradigm for producing therapeutic proteins, due to production cost and product quality related benefits 199:319 Continuous manufacturing is currently being seriously considered in the biopharmaceutical industry as the possible new paradigm for producing therapeutic proteins, due to production cost and product quality related benefits. 27497430 2 33 theme affinity 444:451 arg1 step 461:464 a continuous affinity capture step 431:464 a continuous affinity capture step 431:464 In this study, a monoclonal antibody producing CHO cell line was cultured in perfusion mode and connected to a continuous affinity capture step. 27497430 1 34 theme related 304:310 arg1 benefits 312:319 product quality related benefits 288:319 product quality related benefits 288:319 Continuous manufacturing is currently being seriously considered in the biopharmaceutical industry as the possible new paradigm for producing therapeutic proteins, due to production cost and product quality related benefits. 27497430 6 35 theme isoforms 1193:1200 arg1 terms 1154:1158 terms 1154:1158 terms of aggregates, fragments, charge isoforms, and N-linked glycosylation 1154:1228 Stable operation was achieved at three consecutive viable cell density set points (20, 60, and 40 × 106 cells/mL), together with consistent product quality in terms of aggregates, fragments, charge isoforms, and N-linked glycosylation. 27497430 6 36 theme consistent 1124:1133 arg1 quality 1143:1149 consistent product quality 1124:1149 consistent product quality in terms of aggregates, fragments, charge isoforms, and N-linked glycosylation 1124:1228 Stable operation was achieved at three consecutive viable cell density set points (20, 60, and 40 × 106 cells/mL), together with consistent product quality in terms of aggregates, fragments, charge isoforms, and N-linked glycosylation. 27497430 6 37 theme N-linked 1207:1214 arg1 glycosylation 1216:1228 N-linked glycosylation 1207:1228 N-linked glycosylation 1207:1228 Stable operation was achieved at three consecutive viable cell density set points (20, 60, and 40 × 106 cells/mL), together with consistent product quality in terms of aggregates, fragments, charge isoforms, and N-linked glycosylation. 27497430 3 38 theme reliable 471:478 arg1 integration 491:501 The reliable and stable integration 467:501 The reliable and stable integration of the two systems 467:520 The reliable and stable integration of the two systems was enabled by suitable control loops, regulating the continuous volumetric flow and adapting the operating conditions of the capture process. 27497430 2 39 theme continuous 433:442 arg1 step 461:464 a continuous affinity capture step 431:464 a continuous affinity capture step 431:464 In this study, a monoclonal antibody producing CHO cell line was cultured in perfusion mode and connected to a continuous affinity capture step. 27497430 6 40 link N-linked 1207:1214 arg1 glycosylation 1216:1228 N-linked glycosylation 1207:1228 N-linked glycosylation 1207:1228 Stable operation was achieved at three consecutive viable cell density set points (20, 60, and 40 × 106 cells/mL), together with consistent product quality in terms of aggregates, fragments, charge isoforms, and N-linked glycosylation. 27497430 3 41 theme process 656:662 arg1 conditions 630:639 the operating conditions 616:639 the operating conditions of the capture process 616:662 The reliable and stable integration of the two systems was enabled by suitable control loops, regulating the continuous volumetric flow and adapting the operating conditions of the capture process. 27497430 3 42 theme systems 514:520 arg1 integration 491:501 The reliable and stable integration 467:501 The reliable and stable integration of the two systems 467:520 The reliable and stable integration of the two systems was enabled by suitable control loops, regulating the continuous volumetric flow and adapting the operating conditions of the capture process. 27497430 6 43 from quality 1143:1149 arg1 terms 1154:1158 terms 1154:1158 terms of aggregates, fragments, charge isoforms, and N-linked glycosylation 1154:1228 Stable operation was achieved at three consecutive viable cell density set points (20, 60, and 40 × 106 cells/mL), together with consistent product quality in terms of aggregates, fragments, charge isoforms, and N-linked glycosylation. 27497430 6 44 theme density 1058:1064 arg1 cells/mL 1099:1106 20, 60, and 40 × 106 cells/mL 1078:1106 20, 60, and 40 × 106 cells/mL 1078:1106 Stable operation was achieved at three consecutive viable cell density set points (20, 60, and 40 × 106 cells/mL), together with consistent product quality in terms of aggregates, fragments, charge isoforms, and N-linked glycosylation. 27497430 6 44 theme density 1058:1064 arg1 points 1070:1075 three consecutive viable cell density set points 1028:1075 three consecutive viable cell density set points (20, 60, and 40 × 106 cells/mL) 1028:1107 Stable operation was achieved at three consecutive viable cell density set points (20, 60, and 40 × 106 cells/mL), together with consistent product quality in terms of aggregates, fragments, charge isoforms, and N-linked glycosylation. 27497430 7 45 theme product 1271:1277 arg1 variants 1337:1344 charge variants 1330:1344 charge variants 1330:1344 In addition, different values for these product quality attributes such as N-linked glycosylation, charge variants, and aggregate content were measured at the different steady states. 27497430 7 45 theme product 1271:1277 arg1 attributes 1287:1296 these product quality attributes 1265:1296 these product quality attributes such as N-linked glycosylation, charge variants, and aggregate content 1265:1367 In addition, different values for these product quality attributes such as N-linked glycosylation, charge variants, and aggregate content were measured at the different steady states. 27497430 7 45 theme product 1271:1277 arg1 content 1361:1367 aggregate content 1351:1367 aggregate content 1351:1367 In addition, different values for these product quality attributes such as N-linked glycosylation, charge variants, and aggregate content were measured at the different steady states. 27497430 7 45 theme product 1271:1277 arg1 glycosylation 1315:1327 N-linked glycosylation 1306:1327 N-linked glycosylation 1306:1327 In addition, different values for these product quality attributes such as N-linked glycosylation, charge variants, and aggregate content were measured at the different steady states. 27497430 8 46 theme considered 1517:1526 arg1 conditions 1547:1556 all considered upstream operating conditions 1513:1556 all considered upstream operating conditions 1513:1556 As expected, the amount of released DNA and HCP was significantly reduced by the capture step for all considered upstream operating conditions. 27497430 9 47 theme continuous 1667:1676 arg1 manufacturing 1678:1690 integrated continuous manufacturing 1656:1690 integrated continuous manufacturing 1656:1690 This study is exemplary for the potential of enhancing product quality control and modulation by integrated continuous manufacturing. 27497430 6 48 theme cell 1053:1056 arg1 cells/mL 1099:1106 20, 60, and 40 × 106 cells/mL 1078:1106 20, 60, and 40 × 106 cells/mL 1078:1106 Stable operation was achieved at three consecutive viable cell density set points (20, 60, and 40 × 106 cells/mL), together with consistent product quality in terms of aggregates, fragments, charge isoforms, and N-linked glycosylation. 27497430 6 48 theme cell 1053:1056 arg1 points 1070:1075 three consecutive viable cell density set points 1028:1075 three consecutive viable cell density set points (20, 60, and 40 × 106 cells/mL) 1028:1107 Stable operation was achieved at three consecutive viable cell density set points (20, 60, and 40 × 106 cells/mL), together with consistent product quality in terms of aggregates, fragments, charge isoforms, and N-linked glycosylation. 27497430 4 49 theme chromatographic 820:834 arg1 unit 836:839 the capture chromatographic unit 808:839 the capture chromatographic unit 808:839 For the latter, an at-line HPLC measurement of the harvest concentration subsequent to the bioreactor was combined with a mechanistic model of the capture chromatographic unit. 27497430 5 50 theme optimal 851:857 arg1 consumption 866:876 optimal buffer consumption 851:876 optimal buffer consumption 851:876 Thereby, optimal buffer consumption and productivity throughout the process was realized while always maintaining a yield above the target value of 99%. 27497430 0 51 theme product 24:30 arg1 quality 32:38 product quality 24:38 product quality 24:38 Process performance and product quality in an integrated continuous antibody production process. 27497430 7 52 theme aggregate 1351:1359 arg1 content 1361:1367 aggregate content 1351:1367 aggregate content 1351:1367 In addition, different values for these product quality attributes such as N-linked glycosylation, charge variants, and aggregate content were measured at the different steady states. 27497430 1 53 theme therapeutic 239:249 arg1 proteins 251:258 therapeutic proteins 239:258 therapeutic proteins 239:258 Continuous manufacturing is currently being seriously considered in the biopharmaceutical industry as the possible new paradigm for producing therapeutic proteins, due to production cost and product quality related benefits. 27497430 0 54 theme integrated 46:55 arg1 process 88:94 an integrated continuous antibody production process 43:94 an integrated continuous antibody production process 43:94 Process performance and product quality in an integrated continuous antibody production process. 27497430 8 55 theme operating 1537:1545 arg1 conditions 1547:1556 all considered upstream operating conditions 1513:1556 all considered upstream operating conditions 1513:1556 As expected, the amount of released DNA and HCP was significantly reduced by the capture step for all considered upstream operating conditions. 27497430 6 56 theme viable 1046:1051 arg1 cells/mL 1099:1106 20, 60, and 40 × 106 cells/mL 1078:1106 20, 60, and 40 × 106 cells/mL 1078:1106 Stable operation was achieved at three consecutive viable cell density set points (20, 60, and 40 × 106 cells/mL), together with consistent product quality in terms of aggregates, fragments, charge isoforms, and N-linked glycosylation. 27497430 6 56 theme viable 1046:1051 arg1 points 1070:1075 three consecutive viable cell density set points 1028:1075 three consecutive viable cell density set points (20, 60, and 40 × 106 cells/mL) 1028:1107 Stable operation was achieved at three consecutive viable cell density set points (20, 60, and 40 × 106 cells/mL), together with consistent product quality in terms of aggregates, fragments, charge isoforms, and N-linked glycosylation. 27497430 3 57 theme capture 648:654 arg1 process 656:662 the capture process 644:662 the capture process 644:662 The reliable and stable integration of the two systems was enabled by suitable control loops, regulating the continuous volumetric flow and adapting the operating conditions of the capture process. 27497430 3 58 theme volumetric 587:596 arg1 flow 598:601 the continuous volumetric flow 572:601 the continuous volumetric flow 572:601 The reliable and stable integration of the two systems was enabled by suitable control loops, regulating the continuous volumetric flow and adapting the operating conditions of the capture process. 27497430 8 59 theme released 1442:1449 arg1 DNA 1451:1453 released DNA 1442:1453 released DNA 1442:1453 As expected, the amount of released DNA and HCP was significantly reduced by the capture step for all considered upstream operating conditions. 27497430 4 60 theme unit 836:839 arg1 model 799:803 a mechanistic model 785:803 a mechanistic model of the capture chromatographic unit 785:839 For the latter, an at-line HPLC measurement of the harvest concentration subsequent to the bioreactor was combined with a mechanistic model of the capture chromatographic unit. 27497430 4 61 theme concentration 724:736 arg1 measurement 697:707 an at-line HPLC measurement 681:707 an at-line HPLC measurement of the harvest concentration subsequent to the bioreactor 681:765 For the latter, an at-line HPLC measurement of the harvest concentration subsequent to the bioreactor was combined with a mechanistic model of the capture chromatographic unit. 27497430 7 62 theme charge 1330:1335 arg1 variants 1337:1344 charge variants 1330:1344 charge variants 1330:1344 In addition, different values for these product quality attributes such as N-linked glycosylation, charge variants, and aggregate content were measured at the different steady states. 27497430 6 63 theme charge 1186:1191 arg1 isoforms 1193:1200 charge isoforms 1186:1200 charge isoforms 1186:1200 Stable operation was achieved at three consecutive viable cell density set points (20, 60, and 40 × 106 cells/mL), together with consistent product quality in terms of aggregates, fragments, charge isoforms, and N-linked glycosylation. 27497430 4 64 theme capture 812:818 arg1 unit 836:839 the capture chromatographic unit 808:839 the capture chromatographic unit 808:839 For the latter, an at-line HPLC measurement of the harvest concentration subsequent to the bioreactor was combined with a mechanistic model of the capture chromatographic unit. 27497430 2 65 theme monoclonal 339:348 arg1 antibody 350:357 a monoclonal antibody 337:357 a monoclonal antibody producing CHO cell line 337:381 In this study, a monoclonal antibody producing CHO cell line was cultured in perfusion mode and connected to a continuous affinity capture step. 27497430 12 66 dep 298-307 1723:1729 arg1 2017 1713:1716 2017 1713:1716 2017 1713:1716 2017;114: 298-307. 27497430 6 67 theme consecutive 1034:1044 arg1 cells/mL 1099:1106 20, 60, and 40 × 106 cells/mL 1078:1106 20, 60, and 40 × 106 cells/mL 1078:1106 Stable operation was achieved at three consecutive viable cell density set points (20, 60, and 40 × 106 cells/mL), together with consistent product quality in terms of aggregates, fragments, charge isoforms, and N-linked glycosylation. 27497430 6 67 theme consecutive 1034:1044 arg1 points 1070:1075 three consecutive viable cell density set points 1028:1075 three consecutive viable cell density set points (20, 60, and 40 × 106 cells/mL) 1028:1107 Stable operation was achieved at three consecutive viable cell density set points (20, 60, and 40 × 106 cells/mL), together with consistent product quality in terms of aggregates, fragments, charge isoforms, and N-linked glycosylation. 27497430 5 68 theme % 992:992 arg1 value 981:985 the target value 970:985 the target value of 99% 970:992 Thereby, optimal buffer consumption and productivity throughout the process was realized while always maintaining a yield above the target value of 99%. 27497430 4 69 theme mechanistic 787:797 arg1 model 799:803 a mechanistic model 785:803 a mechanistic model of the capture chromatographic unit 785:839 For the latter, an at-line HPLC measurement of the harvest concentration subsequent to the bioreactor was combined with a mechanistic model of the capture chromatographic unit. 27497430 3 70 dep loops 554:558 arg1 regulating 561:570 regulating 561:570 regulating the continuous volumetric flow 561:601 The reliable and stable integration of the two systems was enabled by suitable control loops, regulating the continuous volumetric flow and adapting the operating conditions of the capture process. 27497430 3 70 dep loops 554:558 arg1 adapting 607:614 adapting 607:614 adapting the operating conditions of the capture process 607:662 The reliable and stable integration of the two systems was enabled by suitable control loops, regulating the continuous volumetric flow and adapting the operating conditions of the capture process. 27497430 3 71 theme stable 484:489 arg1 integration 491:501 The reliable and stable integration 467:501 The reliable and stable integration of the two systems 467:520 The reliable and stable integration of the two systems was enabled by suitable control loops, regulating the continuous volumetric flow and adapting the operating conditions of the capture process. 27497430 0 72 theme antibody 68:75 arg1 process 88:94 an integrated continuous antibody production process 43:94 an integrated continuous antibody production process 43:94 Process performance and product quality in an integrated continuous antibody production process. 27497430 5 73 theme buffer 859:864 arg1 consumption 866:876 optimal buffer consumption 851:876 optimal buffer consumption 851:876 Thereby, optimal buffer consumption and productivity throughout the process was realized while always maintaining a yield above the target value of 99%. 27497430 6 74 theme fragments 1175:1183 arg1 terms 1154:1158 terms 1154:1158 terms of aggregates, fragments, charge isoforms, and N-linked glycosylation 1154:1228 Stable operation was achieved at three consecutive viable cell density set points (20, 60, and 40 × 106 cells/mL), together with consistent product quality in terms of aggregates, fragments, charge isoforms, and N-linked glycosylation. 27497430 6 75 theme set 1066:1068 arg1 cells/mL 1099:1106 20, 60, and 40 × 106 cells/mL 1078:1106 20, 60, and 40 × 106 cells/mL 1078:1106 Stable operation was achieved at three consecutive viable cell density set points (20, 60, and 40 × 106 cells/mL), together with consistent product quality in terms of aggregates, fragments, charge isoforms, and N-linked glycosylation. 27497430 6 75 theme set 1066:1068 arg1 points 1070:1075 three consecutive viable cell density set points 1028:1075 three consecutive viable cell density set points (20, 60, and 40 × 106 cells/mL) 1028:1107 Stable operation was achieved at three consecutive viable cell density set points (20, 60, and 40 × 106 cells/mL), together with consistent product quality in terms of aggregates, fragments, charge isoforms, and N-linked glycosylation. 27497430 4 76 theme at-line 684:690 arg1 measurement 697:707 an at-line HPLC measurement 681:707 an at-line HPLC measurement of the harvest concentration subsequent to the bioreactor 681:765 For the latter, an at-line HPLC measurement of the harvest concentration subsequent to the bioreactor was combined with a mechanistic model of the capture chromatographic unit. 27497430 7 77 theme quality 1279:1285 arg1 variants 1337:1344 charge variants 1330:1344 charge variants 1330:1344 In addition, different values for these product quality attributes such as N-linked glycosylation, charge variants, and aggregate content were measured at the different steady states. 27497430 7 77 theme quality 1279:1285 arg1 attributes 1287:1296 these product quality attributes 1265:1296 these product quality attributes such as N-linked glycosylation, charge variants, and aggregate content 1265:1367 In addition, different values for these product quality attributes such as N-linked glycosylation, charge variants, and aggregate content were measured at the different steady states. 27497430 7 77 theme quality 1279:1285 arg1 content 1361:1367 aggregate content 1351:1367 aggregate content 1351:1367 In addition, different values for these product quality attributes such as N-linked glycosylation, charge variants, and aggregate content were measured at the different steady states. 27497430 7 77 theme quality 1279:1285 arg1 glycosylation 1315:1327 N-linked glycosylation 1306:1327 N-linked glycosylation 1306:1327 In addition, different values for these product quality attributes such as N-linked glycosylation, charge variants, and aggregate content were measured at the different steady states. 27497430 0 78 theme continuous 57:66 arg1 process 88:94 an integrated continuous antibody production process 43:94 an integrated continuous antibody production process 43:94 Process performance and product quality in an integrated continuous antibody production process. 27497430 3 79 theme operating 620:628 arg1 conditions 630:639 the operating conditions 616:639 the operating conditions of the capture process 616:662 The reliable and stable integration of the two systems was enabled by suitable control loops, regulating the continuous volumetric flow and adapting the operating conditions of the capture process. 27497430 6 80 theme aggregates 1163:1172 arg1 terms 1154:1158 terms 1154:1158 terms of aggregates, fragments, charge isoforms, and N-linked glycosylation 1154:1228 Stable operation was achieved at three consecutive viable cell density set points (20, 60, and 40 × 106 cells/mL), together with consistent product quality in terms of aggregates, fragments, charge isoforms, and N-linked glycosylation. 27497430 3 81 theme continuous 576:585 arg1 flow 598:601 the continuous volumetric flow 572:601 the continuous volumetric flow 572:601 The reliable and stable integration of the two systems was enabled by suitable control loops, regulating the continuous volumetric flow and adapting the operating conditions of the capture process. 24913938 9 0 theme high 1450:1453 arg1 degree 1455:1460 its high degree 1446:1460 its high degree of pubescence 1446:1474 For the adaxial side, it is concluded that trichomes and the scars after trichome shedding contribute to water uptake, while the abaxial leaf side is highly hydrophobic due to its high degree of pubescence and different trichome structure, composition, and density. 24913938 3 1 theme water 492:496 arg1 drops 498:502 water drops 492:502 water drops 492:502 By measuring the leaf water potential 24 h after the deposition of water drops onto abaxial and adaxial surfaces, evidence for water penetration through the upper leaf side was gained in young and mature leaves. 24913938 6 2 theme leaf 1057:1060 arg1 age 1062:1064 leaf age 1057:1064 leaf age 1057:1064 The surface free energy and solubility parameter decreased with leaf age, with higher values determined for the adaxial sides. 24913938 5 3 contain had 866:868 arg1 surfaces 839:846 The adaxial surfaces 827:846 The adaxial surfaces 827:846 The adaxial surfaces were wettable and had a high degree of water drop adhesion in contrast to the highly unwettable and water-repellent abaxial holm oak leaf sides. 24913938 5 3 contain had 866:868 arg1 wettable 853:860 wettable 853:860 wettable 853:860 The adaxial surfaces were wettable and had a high degree of water drop adhesion in contrast to the highly unwettable and water-repellent abaxial holm oak leaf sides. 24913938 5 3 contain had 866:868 arg2 degree 877:882 a high degree 870:882 a high degree of water drop adhesion 870:905 The adaxial surfaces were wettable and had a high degree of water drop adhesion in contrast to the highly unwettable and water-repellent abaxial holm oak leaf sides. 24913938 9 4 theme trichome 1490:1497 arg1 structure 1499:1507 different trichome structure 1480:1507 different trichome structure 1480:1507 For the adaxial side, it is concluded that trichomes and the scars after trichome shedding contribute to water uptake, while the abaxial leaf side is highly hydrophobic due to its high degree of pubescence and different trichome structure, composition, and density. 24913938 10 5 theme interactions 1592:1603 arg1 terms 1563:1567 terms 1563:1567 terms of water-plant surface interactions, plant surface physical chemistry, and plant ecophysiology 1563:1662 Results are interpreted in terms of water-plant surface interactions, plant surface physical chemistry, and plant ecophysiology. 24913938 4 6 dep abaxial 683:689 arg1 present 699:705 present 699:705 present 699:705 The structure and chemical composition of the abaxial (always present) and adaxial (occurring only in young leaves) trichomes were analyzed by various microscopic and analytical procedures. 24913938 4 7 theme analytical 804:813 arg1 procedures 815:824 various microscopic and analytical procedures 780:824 various microscopic and analytical procedures 780:824 The structure and chemical composition of the abaxial (always present) and adaxial (occurring only in young leaves) trichomes were analyzed by various microscopic and analytical procedures. 24913938 3 8 theme drops 498:502 arg1 deposition 478:487 the deposition 474:487 the deposition of water drops onto abaxial and adaxial surfaces 474:536 By measuring the leaf water potential 24 h after the deposition of water drops onto abaxial and adaxial surfaces, evidence for water penetration through the upper leaf side was gained in young and mature leaves. 24913938 6 9 theme solubility 1021:1030 arg1 parameter 1032:1040 solubility parameter 1021:1040 solubility parameter 1021:1040 The surface free energy and solubility parameter decreased with leaf age, with higher values determined for the adaxial sides. 24913938 5 10 theme adaxial 831:837 arg1 surfaces 839:846 The adaxial surfaces 827:846 The adaxial surfaces 827:846 The adaxial surfaces were wettable and had a high degree of water drop adhesion in contrast to the highly unwettable and water-repellent abaxial holm oak leaf sides. 24913938 5 10 theme adaxial 831:837 arg1 wettable 853:860 wettable 853:860 wettable 853:860 The adaxial surfaces were wettable and had a high degree of water drop adhesion in contrast to the highly unwettable and water-repellent abaxial holm oak leaf sides. 24913938 10 11 theme water-plant 1572:1582 arg1 interactions 1592:1603 water-plant surface interactions 1572:1603 water-plant surface interactions 1572:1603 Results are interpreted in terms of water-plant surface interactions, plant surface physical chemistry, and plant ecophysiology. 24913938 1 12 theme major 160:164 arg1 influence 166:174 a major influence 158:174 a major influence 158:174 Plant trichomes play important protective functions and may have a major influence on leaf surface wettability. 24913938 5 13 theme abaxial 964:970 arg1 sides 986:990 the highly unwettable and water-repellent abaxial holm oak leaf sides 922:990 the highly unwettable and water-repellent abaxial holm oak leaf sides 922:990 The adaxial surfaces were wettable and had a high degree of water drop adhesion in contrast to the highly unwettable and water-repellent abaxial holm oak leaf sides. 24913938 3 14 theme abaxial 509:515 arg1 surfaces 529:536 abaxial and adaxial surfaces 509:536 abaxial and adaxial surfaces 509:536 By measuring the leaf water potential 24 h after the deposition of water drops onto abaxial and adaxial surfaces, evidence for water penetration through the upper leaf side was gained in young and mature leaves. 24913938 10 15 theme plant 1606:1610 arg1 chemistry 1629:1637 plant surface physical chemistry 1606:1637 plant surface physical chemistry 1606:1637 Results are interpreted in terms of water-plant surface interactions, plant surface physical chemistry, and plant ecophysiology. 24913938 4 16 dep structure 641:649 arg1 The 637:639 The 637:639 The 637:639 The structure and chemical composition of the abaxial (always present) and adaxial (occurring only in young leaves) trichomes were analyzed by various microscopic and analytical procedures. 24913938 4 17 theme microscopic 788:798 arg1 procedures 815:824 various microscopic and analytical procedures 780:824 various microscopic and analytical procedures 780:824 The structure and chemical composition of the abaxial (always present) and adaxial (occurring only in young leaves) trichomes were analyzed by various microscopic and analytical procedures. 24913938 10 18 theme plant 1644:1648 arg1 ecophysiology 1650:1662 plant ecophysiology 1644:1662 plant ecophysiology 1644:1662 Results are interpreted in terms of water-plant surface interactions, plant surface physical chemistry, and plant ecophysiology. 24913938 3 19 dep h 466:466 arg1 deposition 478:487 the deposition 474:487 the deposition of water drops onto abaxial and adaxial surfaces 474:536 By measuring the leaf water potential 24 h after the deposition of water drops onto abaxial and adaxial surfaces, evidence for water penetration through the upper leaf side was gained in young and mature leaves. 24913938 6 20 theme higher 1072:1077 arg1 values 1079:1084 higher values 1072:1084 higher values determined for the adaxial sides 1072:1117 The surface free energy and solubility parameter decreased with leaf age, with higher values determined for the adaxial sides. 24913938 8 21 theme abaxial 1181:1187 arg1 trichomes 1189:1197 The abaxial trichomes 1177:1197 The abaxial trichomes 1177:1197 The abaxial trichomes were composed of 8% soluble waxes, 49% cutin, and 43% polysaccharides. 24913938 0 22 theme holm 47:50 arg1 oak 52:54 holm oak 47:54 holm oak 47:54 Wettability, polarity, and water absorption of holm oak leaves: effect of leaf side and age. 24913938 3 23 theme adaxial 521:527 arg1 surfaces 529:536 abaxial and adaxial surfaces 509:536 abaxial and adaxial surfaces 509:536 By measuring the leaf water potential 24 h after the deposition of water drops onto abaxial and adaxial surfaces, evidence for water penetration through the upper leaf side was gained in young and mature leaves. 24913938 1 24 theme protective 124:133 arg1 functions 135:143 important protective functions 114:143 important protective functions 114:143 Plant trichomes play important protective functions and may have a major influence on leaf surface wettability. 24913938 1 25 contain have 153:156 arg2 influence 166:174 a major influence 158:174 a major influence 158:174 Plant trichomes play important protective functions and may have a major influence on leaf surface wettability. 24913938 1 25 contain have 153:156 arg1 trichomes 99:107 Plant trichomes 93:107 Plant trichomes 93:107 Plant trichomes play important protective functions and may have a major influence on leaf surface wettability. 24913938 5 26 theme oak 977:979 arg1 sides 986:990 the highly unwettable and water-repellent abaxial holm oak leaf sides 922:990 the highly unwettable and water-repellent abaxial holm oak leaf sides 922:990 The adaxial surfaces were wettable and had a high degree of water drop adhesion in contrast to the highly unwettable and water-repellent abaxial holm oak leaf sides. 24913938 1 27 theme Plant 93:97 arg1 trichomes 99:107 Plant trichomes 93:107 Plant trichomes 93:107 Plant trichomes play important protective functions and may have a major influence on leaf surface wettability. 24913938 8 28 theme % 1217:1217 arg1 polysaccharides 1253:1267 8% soluble waxes, 49% cutin, and 43% polysaccharides 1216:1267 8% soluble waxes, 49% cutin, and 43% polysaccharides 1216:1267 The abaxial trichomes were composed of 8% soluble waxes, 49% cutin, and 43% polysaccharides. 24913938 0 29 theme leaf 74:77 arg1 side 79:82 leaf side 74:82 leaf side 74:82 Wettability, polarity, and water absorption of holm oak leaves: effect of leaf side and age. 24913938 2 30 theme oak 394:396 arg1 model 418:422 a model 416:422 a model 416:422 With the aim of gaining insight into trichome structure, composition, and function in relation to water-plant surface interactions, we analyzed the adaxial and abaxial leaf surface of holm oak (Quercus ilex) as a model. 24913938 2 30 theme oak 394:396 arg1 surface 378:384 the adaxial and abaxial leaf surface 349:384 the adaxial and abaxial leaf surface of holm oak (Quercus ilex) 349:411 With the aim of gaining insight into trichome structure, composition, and function in relation to water-plant surface interactions, we analyzed the adaxial and abaxial leaf surface of holm oak (Quercus ilex) as a model. 24913938 0 31 dep leaves 56:61 arg1 effect 64:69 effect 64:69 effect of leaf side and age 64:90 Wettability, polarity, and water absorption of holm oak leaves: effect of leaf side and age. 24913938 5 32 theme drop 893:896 arg1 adhesion 898:905 water drop adhesion 887:905 water drop adhesion 887:905 The adaxial surfaces were wettable and had a high degree of water drop adhesion in contrast to the highly unwettable and water-repellent abaxial holm oak leaf sides. 24913938 2 33 theme leaf 373:376 arg1 model 418:422 a model 416:422 a model 416:422 With the aim of gaining insight into trichome structure, composition, and function in relation to water-plant surface interactions, we analyzed the adaxial and abaxial leaf surface of holm oak (Quercus ilex) as a model. 24913938 2 33 theme leaf 373:376 arg1 surface 378:384 the adaxial and abaxial leaf surface 349:384 the adaxial and abaxial leaf surface of holm oak (Quercus ilex) 349:411 With the aim of gaining insight into trichome structure, composition, and function in relation to water-plant surface interactions, we analyzed the adaxial and abaxial leaf surface of holm oak (Quercus ilex) as a model. 24913938 9 34 theme abaxial 1399:1405 arg1 side 1412:1415 the abaxial leaf side 1395:1415 the abaxial leaf side 1395:1415 For the adaxial side, it is concluded that trichomes and the scars after trichome shedding contribute to water uptake, while the abaxial leaf side is highly hydrophobic due to its high degree of pubescence and different trichome structure, composition, and density. 24913938 9 34 theme abaxial 1399:1405 arg1 hydrophobic 1427:1437 hydrophobic 1427:1437 hydrophobic 1427:1437 For the adaxial side, it is concluded that trichomes and the scars after trichome shedding contribute to water uptake, while the abaxial leaf side is highly hydrophobic due to its high degree of pubescence and different trichome structure, composition, and density. 24913938 8 35 theme cutin 1238:1242 arg1 % 1236:1236 49% cutin 1234:1242 49% cutin 1234:1242 The abaxial trichomes were composed of 8% soluble waxes, 49% cutin, and 43% polysaccharides. 24913938 3 36 dep young 612:616 arg1 leaves 629:634 leaves 629:634 leaves 629:634 By measuring the leaf water potential 24 h after the deposition of water drops onto abaxial and adaxial surfaces, evidence for water penetration through the upper leaf side was gained in young and mature leaves. 24913938 5 37 theme adhesion 898:905 arg1 degree 877:882 a high degree 870:882 a high degree of water drop adhesion 870:905 The adaxial surfaces were wettable and had a high degree of water drop adhesion in contrast to the highly unwettable and water-repellent abaxial holm oak leaf sides. 24913938 2 38 theme Quercus 399:405 arg1 oak 394:396 holm oak 389:396 holm oak (Quercus ilex) 389:411 With the aim of gaining insight into trichome structure, composition, and function in relation to water-plant surface interactions, we analyzed the adaxial and abaxial leaf surface of holm oak (Quercus ilex) as a model. 24913938 2 38 theme Quercus 399:405 arg1 ilex 407:410 Quercus ilex 399:410 Quercus ilex 399:410 With the aim of gaining insight into trichome structure, composition, and function in relation to water-plant surface interactions, we analyzed the adaxial and abaxial leaf surface of holm oak (Quercus ilex) as a model. 24913938 9 39 theme pubescence 1465:1474 arg1 composition 1510:1520 composition 1510:1520 composition 1510:1520 For the adaxial side, it is concluded that trichomes and the scars after trichome shedding contribute to water uptake, while the abaxial leaf side is highly hydrophobic due to its high degree of pubescence and different trichome structure, composition, and density. 24913938 9 39 theme pubescence 1465:1474 arg1 degree 1455:1460 its high degree 1446:1460 its high degree of pubescence 1446:1474 For the adaxial side, it is concluded that trichomes and the scars after trichome shedding contribute to water uptake, while the abaxial leaf side is highly hydrophobic due to its high degree of pubescence and different trichome structure, composition, and density. 24913938 9 39 theme pubescence 1465:1474 arg1 density 1527:1533 density 1527:1533 density 1527:1533 For the adaxial side, it is concluded that trichomes and the scars after trichome shedding contribute to water uptake, while the abaxial leaf side is highly hydrophobic due to its high degree of pubescence and different trichome structure, composition, and density. 24913938 9 39 theme pubescence 1465:1474 arg1 structure 1499:1507 different trichome structure 1480:1507 different trichome structure 1480:1507 For the adaxial side, it is concluded that trichomes and the scars after trichome shedding contribute to water uptake, while the abaxial leaf side is highly hydrophobic due to its high degree of pubescence and different trichome structure, composition, and density. 24913938 6 40 theme free 1005:1008 arg1 energy 1010:1015 The surface free energy 993:1015 The surface free energy 993:1015 The surface free energy and solubility parameter decreased with leaf age, with higher values determined for the adaxial sides. 24913938 3 41 theme leaf 588:591 arg1 side 593:596 the upper leaf side 578:596 the upper leaf side 578:596 By measuring the leaf water potential 24 h after the deposition of water drops onto abaxial and adaxial surfaces, evidence for water penetration through the upper leaf side was gained in young and mature leaves. 24913938 8 42 theme % 1251:1251 arg1 polysaccharides 1253:1267 8% soluble waxes, 49% cutin, and 43% polysaccharides 1216:1267 8% soluble waxes, 49% cutin, and 43% polysaccharides 1216:1267 The abaxial trichomes were composed of 8% soluble waxes, 49% cutin, and 43% polysaccharides. 24913938 1 43 theme leaf 179:182 arg1 wettability 192:202 leaf surface wettability 179:202 leaf surface wettability 179:202 Plant trichomes play important protective functions and may have a major influence on leaf surface wettability. 24913938 5 44 theme water 887:891 arg1 adhesion 898:905 water drop adhesion 887:905 water drop adhesion 887:905 The adaxial surfaces were wettable and had a high degree of water drop adhesion in contrast to the highly unwettable and water-repellent abaxial holm oak leaf sides. 24913938 7 45 theme oak 1129:1131 arg1 trichomes 1138:1146 All holm oak leaf trichomes 1120:1146 All holm oak leaf trichomes 1120:1146 All holm oak leaf trichomes were covered with a cuticle. 24913938 2 46 theme water-plant 303:313 arg1 interactions 323:334 water-plant surface interactions 303:334 water-plant surface interactions 303:334 With the aim of gaining insight into trichome structure, composition, and function in relation to water-plant surface interactions, we analyzed the adaxial and abaxial leaf surface of holm oak (Quercus ilex) as a model. 24913938 2 47 theme trichome 242:249 arg1 structure 251:259 trichome structure 242:259 trichome structure 242:259 With the aim of gaining insight into trichome structure, composition, and function in relation to water-plant surface interactions, we analyzed the adaxial and abaxial leaf surface of holm oak (Quercus ilex) as a model. 24913938 4 48 theme trichomes 753:761 arg1 structure 641:649 structure 641:649 structure 641:649 The structure and chemical composition of the abaxial (always present) and adaxial (occurring only in young leaves) trichomes were analyzed by various microscopic and analytical procedures. 24913938 4 48 theme trichomes 753:761 arg1 composition 664:674 chemical composition 655:674 chemical composition 655:674 The structure and chemical composition of the abaxial (always present) and adaxial (occurring only in young leaves) trichomes were analyzed by various microscopic and analytical procedures. 24913938 9 49 theme trichome 1343:1350 arg1 shedding 1352:1359 trichome shedding 1343:1359 trichome shedding 1343:1359 For the adaxial side, it is concluded that trichomes and the scars after trichome shedding contribute to water uptake, while the abaxial leaf side is highly hydrophobic due to its high degree of pubescence and different trichome structure, composition, and density. 24913938 3 50 theme water 447:451 arg1 potential 453:461 the leaf water potential 438:461 the leaf water potential 438:461 By measuring the leaf water potential 24 h after the deposition of water drops onto abaxial and adaxial surfaces, evidence for water penetration through the upper leaf side was gained in young and mature leaves. 24913938 4 51 dep present 699:705 arg1 always 692:697 always 692:697 always 692:697 The structure and chemical composition of the abaxial (always present) and adaxial (occurring only in young leaves) trichomes were analyzed by various microscopic and analytical procedures. 24913938 9 52 theme different 1480:1488 arg1 structure 1499:1507 different trichome structure 1480:1507 different trichome structure 1480:1507 For the adaxial side, it is concluded that trichomes and the scars after trichome shedding contribute to water uptake, while the abaxial leaf side is highly hydrophobic due to its high degree of pubescence and different trichome structure, composition, and density. 24913938 9 53 theme adaxial 1278:1284 arg1 side 1286:1289 the adaxial side 1274:1289 the adaxial side 1274:1289 For the adaxial side, it is concluded that trichomes and the scars after trichome shedding contribute to water uptake, while the abaxial leaf side is highly hydrophobic due to its high degree of pubescence and different trichome structure, composition, and density. 24913938 0 54 theme age 88:90 arg1 effect 64:69 effect 64:69 effect of leaf side and age 64:90 Wettability, polarity, and water absorption of holm oak leaves: effect of leaf side and age. 24913938 10 55 theme surface 1584:1590 arg1 interactions 1592:1603 water-plant surface interactions 1572:1603 water-plant surface interactions 1572:1603 Results are interpreted in terms of water-plant surface interactions, plant surface physical chemistry, and plant ecophysiology. 24913938 8 56 dep % 1217:1217 arg1 waxes 1227:1231 soluble waxes 1219:1231 8% soluble waxes 1216:1231 The abaxial trichomes were composed of 8% soluble waxes, 49% cutin, and 43% polysaccharides. 24913938 5 57 theme water-repellent 948:962 arg1 sides 986:990 the highly unwettable and water-repellent abaxial holm oak leaf sides 922:990 the highly unwettable and water-repellent abaxial holm oak leaf sides 922:990 The adaxial surfaces were wettable and had a high degree of water drop adhesion in contrast to the highly unwettable and water-repellent abaxial holm oak leaf sides. 24913938 10 58 theme chemistry 1629:1637 arg1 terms 1563:1567 terms 1563:1567 terms of water-plant surface interactions, plant surface physical chemistry, and plant ecophysiology 1563:1662 Results are interpreted in terms of water-plant surface interactions, plant surface physical chemistry, and plant ecophysiology. 24913938 6 59 theme adaxial 1105:1111 arg1 sides 1113:1117 the adaxial sides 1101:1117 the adaxial sides 1101:1117 The surface free energy and solubility parameter decreased with leaf age, with higher values determined for the adaxial sides. 24913938 5 60 theme holm 972:975 arg1 sides 986:990 the highly unwettable and water-repellent abaxial holm oak leaf sides 922:990 the highly unwettable and water-repellent abaxial holm oak leaf sides 922:990 The adaxial surfaces were wettable and had a high degree of water drop adhesion in contrast to the highly unwettable and water-repellent abaxial holm oak leaf sides. 24913938 10 61 theme surface 1612:1618 arg1 chemistry 1629:1637 plant surface physical chemistry 1606:1637 plant surface physical chemistry 1606:1637 Results are interpreted in terms of water-plant surface interactions, plant surface physical chemistry, and plant ecophysiology. 24913938 10 62 theme ecophysiology 1650:1662 arg1 terms 1563:1567 terms 1563:1567 terms of water-plant surface interactions, plant surface physical chemistry, and plant ecophysiology 1563:1662 Results are interpreted in terms of water-plant surface interactions, plant surface physical chemistry, and plant ecophysiology. 24913938 4 63 theme various 780:786 arg1 procedures 815:824 various microscopic and analytical procedures 780:824 various microscopic and analytical procedures 780:824 The structure and chemical composition of the abaxial (always present) and adaxial (occurring only in young leaves) trichomes were analyzed by various microscopic and analytical procedures. 24913938 7 64 theme leaf 1133:1136 arg1 trichomes 1138:1146 All holm oak leaf trichomes 1120:1146 All holm oak leaf trichomes 1120:1146 All holm oak leaf trichomes were covered with a cuticle. 24913938 0 65 theme oak 52:54 arg1 polarity 13:20 polarity 13:20 polarity 13:20 Wettability, polarity, and water absorption of holm oak leaves: effect of leaf side and age. 24913938 0 65 theme oak 52:54 arg1 Wettability 0:10 Wettability 0:10 Wettability 0:10 Wettability, polarity, and water absorption of holm oak leaves: effect of leaf side and age. 24913938 0 65 theme oak 52:54 arg1 absorption 33:42 water absorption 27:42 water absorption 27:42 Wettability, polarity, and water absorption of holm oak leaves: effect of leaf side and age. 24913938 5 66 theme unwettable 933:942 arg1 sides 986:990 the highly unwettable and water-repellent abaxial holm oak leaf sides 922:990 the highly unwettable and water-repellent abaxial holm oak leaf sides 922:990 The adaxial surfaces were wettable and had a high degree of water drop adhesion in contrast to the highly unwettable and water-repellent abaxial holm oak leaf sides. 24913938 1 67 theme important 114:122 arg1 functions 135:143 important protective functions 114:143 important protective functions 114:143 Plant trichomes play important protective functions and may have a major influence on leaf surface wettability. 24913938 4 68 theme chemical 655:662 arg1 composition 664:674 chemical composition 655:674 chemical composition 655:674 The structure and chemical composition of the abaxial (always present) and adaxial (occurring only in young leaves) trichomes were analyzed by various microscopic and analytical procedures. 24913938 0 69 theme side 79:82 arg1 effect 64:69 effect 64:69 effect of leaf side and age 64:90 Wettability, polarity, and water absorption of holm oak leaves: effect of leaf side and age. 24913938 5 70 theme leaf 981:984 arg1 sides 986:990 the highly unwettable and water-repellent abaxial holm oak leaf sides 922:990 the highly unwettable and water-repellent abaxial holm oak leaf sides 922:990 The adaxial surfaces were wettable and had a high degree of water drop adhesion in contrast to the highly unwettable and water-repellent abaxial holm oak leaf sides. 24913938 4 71 dep adaxial 712:718 arg1 young 739:743 young 739:743 young 739:743 The structure and chemical composition of the abaxial (always present) and adaxial (occurring only in young leaves) trichomes were analyzed by various microscopic and analytical procedures. 24913938 9 72 theme water 1375:1379 arg1 uptake 1381:1386 water uptake 1375:1386 water uptake 1375:1386 For the adaxial side, it is concluded that trichomes and the scars after trichome shedding contribute to water uptake, while the abaxial leaf side is highly hydrophobic due to its high degree of pubescence and different trichome structure, composition, and density. 24913938 4 73 dep young 739:743 arg1 leaves 745:750 leaves 745:750 leaves 745:750 The structure and chemical composition of the abaxial (always present) and adaxial (occurring only in young leaves) trichomes were analyzed by various microscopic and analytical procedures. 24913938 2 74 theme holm 389:392 arg1 oak 394:396 holm oak 389:396 holm oak (Quercus ilex) 389:411 With the aim of gaining insight into trichome structure, composition, and function in relation to water-plant surface interactions, we analyzed the adaxial and abaxial leaf surface of holm oak (Quercus ilex) as a model. 24913938 2 74 theme holm 389:392 arg1 ilex 407:410 Quercus ilex 399:410 Quercus ilex 399:410 With the aim of gaining insight into trichome structure, composition, and function in relation to water-plant surface interactions, we analyzed the adaxial and abaxial leaf surface of holm oak (Quercus ilex) as a model. 24913938 8 75 theme soluble 1219:1225 arg1 waxes 1227:1231 soluble waxes 1219:1231 8% soluble waxes 1216:1231 The abaxial trichomes were composed of 8% soluble waxes, 49% cutin, and 43% polysaccharides. 24913938 3 76 theme water 552:556 arg1 penetration 558:568 water penetration 552:568 water penetration through the upper leaf side 552:596 By measuring the leaf water potential 24 h after the deposition of water drops onto abaxial and adaxial surfaces, evidence for water penetration through the upper leaf side was gained in young and mature leaves. 24913938 2 77 theme abaxial 365:371 arg1 model 418:422 a model 416:422 a model 416:422 With the aim of gaining insight into trichome structure, composition, and function in relation to water-plant surface interactions, we analyzed the adaxial and abaxial leaf surface of holm oak (Quercus ilex) as a model. 24913938 2 77 theme abaxial 365:371 arg1 surface 378:384 the adaxial and abaxial leaf surface 349:384 the adaxial and abaxial leaf surface of holm oak (Quercus ilex) 349:411 With the aim of gaining insight into trichome structure, composition, and function in relation to water-plant surface interactions, we analyzed the adaxial and abaxial leaf surface of holm oak (Quercus ilex) as a model. 24913938 0 78 theme water 27:31 arg1 absorption 33:42 water absorption 27:42 water absorption 27:42 Wettability, polarity, and water absorption of holm oak leaves: effect of leaf side and age. 24913938 9 79 theme leaf 1407:1410 arg1 side 1412:1415 the abaxial leaf side 1395:1415 the abaxial leaf side 1395:1415 For the adaxial side, it is concluded that trichomes and the scars after trichome shedding contribute to water uptake, while the abaxial leaf side is highly hydrophobic due to its high degree of pubescence and different trichome structure, composition, and density. 24913938 9 79 theme leaf 1407:1410 arg1 hydrophobic 1427:1437 hydrophobic 1427:1437 hydrophobic 1427:1437 For the adaxial side, it is concluded that trichomes and the scars after trichome shedding contribute to water uptake, while the abaxial leaf side is highly hydrophobic due to its high degree of pubescence and different trichome structure, composition, and density. 24913938 8 80 theme % 1236:1236 arg1 polysaccharides 1253:1267 8% soluble waxes, 49% cutin, and 43% polysaccharides 1216:1267 8% soluble waxes, 49% cutin, and 43% polysaccharides 1216:1267 The abaxial trichomes were composed of 8% soluble waxes, 49% cutin, and 43% polysaccharides. 24913938 2 81 theme adaxial 353:359 arg1 model 418:422 a model 416:422 a model 416:422 With the aim of gaining insight into trichome structure, composition, and function in relation to water-plant surface interactions, we analyzed the adaxial and abaxial leaf surface of holm oak (Quercus ilex) as a model. 24913938 2 81 theme adaxial 353:359 arg1 surface 378:384 the adaxial and abaxial leaf surface 349:384 the adaxial and abaxial leaf surface of holm oak (Quercus ilex) 349:411 With the aim of gaining insight into trichome structure, composition, and function in relation to water-plant surface interactions, we analyzed the adaxial and abaxial leaf surface of holm oak (Quercus ilex) as a model. 24913938 3 82 theme upper 582:586 arg1 side 593:596 the upper leaf side 578:596 the upper leaf side 578:596 By measuring the leaf water potential 24 h after the deposition of water drops onto abaxial and adaxial surfaces, evidence for water penetration through the upper leaf side was gained in young and mature leaves. 24913938 4 83 theme adaxial 712:718 arg1 trichomes 753:761 the abaxial (always present) and adaxial (occurring only in young leaves) trichomes 679:761 the abaxial (always present) and adaxial (occurring only in young leaves) trichomes 679:761 The structure and chemical composition of the abaxial (always present) and adaxial (occurring only in young leaves) trichomes were analyzed by various microscopic and analytical procedures. 24913938 5 84 theme high 872:875 arg1 degree 877:882 a high degree 870:882 a high degree of water drop adhesion 870:905 The adaxial surfaces were wettable and had a high degree of water drop adhesion in contrast to the highly unwettable and water-repellent abaxial holm oak leaf sides. 24913938 10 85 theme physical 1620:1627 arg1 chemistry 1629:1637 plant surface physical chemistry 1606:1637 plant surface physical chemistry 1606:1637 Results are interpreted in terms of water-plant surface interactions, plant surface physical chemistry, and plant ecophysiology. 24913938 6 86 theme surface 997:1003 arg1 energy 1010:1015 The surface free energy 993:1015 The surface free energy 993:1015 The surface free energy and solubility parameter decreased with leaf age, with higher values determined for the adaxial sides. 24913938 4 87 theme abaxial 683:689 arg1 trichomes 753:761 the abaxial (always present) and adaxial (occurring only in young leaves) trichomes 679:761 the abaxial (always present) and adaxial (occurring only in young leaves) trichomes 679:761 The structure and chemical composition of the abaxial (always present) and adaxial (occurring only in young leaves) trichomes were analyzed by various microscopic and analytical procedures. 24913938 2 88 theme surface 315:321 arg1 interactions 323:334 water-plant surface interactions 303:334 water-plant surface interactions 303:334 With the aim of gaining insight into trichome structure, composition, and function in relation to water-plant surface interactions, we analyzed the adaxial and abaxial leaf surface of holm oak (Quercus ilex) as a model. 24913938 1 89 theme surface 184:190 arg1 wettability 192:202 leaf surface wettability 179:202 leaf surface wettability 179:202 Plant trichomes play important protective functions and may have a major influence on leaf surface wettability. 24913938 7 90 theme holm 1124:1127 arg1 trichomes 1138:1146 All holm oak leaf trichomes 1120:1146 All holm oak leaf trichomes 1120:1146 All holm oak leaf trichomes were covered with a cuticle. 24913938 3 91 theme leaf 442:445 arg1 potential 453:461 the leaf water potential 438:461 the leaf water potential 438:461 By measuring the leaf water potential 24 h after the deposition of water drops onto abaxial and adaxial surfaces, evidence for water penetration through the upper leaf side was gained in young and mature leaves. 28263870 7 0 theme yeast 1201:1205 arg1 cells 1207:1211 yeast cells 1201:1211 yeast cells 1201:1211 Protein O-GlcNAcylation and the growth defects of yeast cells are caused by the O-GlcNAc transferase activity because catalytically inactive sOGT does not exhibit toxicity in yeast cells. 28263870 1 1 theme O-GlcNAc 156:163 arg1 moiety 165:170 O-GlcNAc moiety 156:170 O-GlcNAc moiety 156:170 BACKGROUND O-GlcNAcylation is a reversible protein post-translational modification, where O-GlcNAc moiety is attached to nucleocytoplasmic protein by O-GlcNAc transferase (OGT) and removed by O-GlcNAcase (OGA). 28263870 6 2 theme yeast 974:978 arg1 proteins 980:987 yeast proteins 974:987 yeast proteins 974:987 The direct analysis of yeast proteins demonstrates protein O-GlcNAcylation is dependent on sOGT expression; conversely, the hydrolysis of these sugar modifications is induced by co-expression of OGA. 28263870 7 3 theme cells 1207:1211 arg1 defects 1190:1196 the growth defects 1179:1196 the growth defects of yeast cells 1179:1211 Protein O-GlcNAcylation and the growth defects of yeast cells are caused by the O-GlcNAc transferase activity because catalytically inactive sOGT does not exhibit toxicity in yeast cells. 28263870 7 3 theme cells 1207:1211 arg1 O-GlcNAcylation 1159:1173 Protein O-GlcNAcylation 1151:1173 Protein O-GlcNAcylation 1151:1173 Protein O-GlcNAcylation and the growth defects of yeast cells are caused by the O-GlcNAc transferase activity because catalytically inactive sOGT does not exhibit toxicity in yeast cells. 28263870 5 4 theme yeast 889:893 arg1 cells 895:899 yeast cells 889:899 yeast cells 889:899 sOGT expression causes a severe growth defect in yeast cells, which is remediated by the co-expression of OGA. 28263870 11 5 theme GENERAL 1655:1661 arg1 cells 1682:1686 GENERAL SIGNIFICANCE Yeast cells 1655:1686 GENERAL SIGNIFICANCE Yeast cells 1655:1686 GENERAL SIGNIFICANCE Yeast cells may be used to assess OGT and OGA. 28263870 7 6 theme yeast 1326:1330 arg1 cells 1332:1336 yeast cells 1326:1336 yeast cells 1326:1336 Protein O-GlcNAcylation and the growth defects of yeast cells are caused by the O-GlcNAc transferase activity because catalytically inactive sOGT does not exhibit toxicity in yeast cells. 28263870 3 7 dep METHODS 482:488 arg1 OGA 513:515 OGA 513:515 OGA 513:515 METHODS Human OGT isoforms and OGA were ectopically expressed in S. cerevisiae, and the effects of their expressions on yeast growth and O-GlcNAc modification levels were assessed. 28263870 3 7 dep METHODS 482:488 arg1 isoforms 500:507 Human OGT isoforms 490:507 Human OGT isoforms 490:507 METHODS Human OGT isoforms and OGA were ectopically expressed in S. cerevisiae, and the effects of their expressions on yeast growth and O-GlcNAc modification levels were assessed. 28263870 4 8 theme proteins 747:754 arg1 modification 731:742 the O-GlcNAc modification 718:742 the O-GlcNAc modification of proteins 718:754 RESULTS Expression of sOGT, in S. cerevisiae catalyzes the O-GlcNAc modification of proteins in vivo; conversely, the expression of OGA mediates the hydrolysis of these sugars. 28263870 6 9 theme OGA 1146:1148 arg1 co-expression 1129:1141 co-expression 1129:1141 co-expression of OGA 1129:1148 The direct analysis of yeast proteins demonstrates protein O-GlcNAcylation is dependent on sOGT expression; conversely, the hydrolysis of these sugar modifications is induced by co-expression of OGA. 28263870 5 10 theme OGA 946:948 arg1 co-expression 929:941 the co-expression 925:941 the co-expression of OGA 925:948 sOGT expression causes a severe growth defect in yeast cells, which is remediated by the co-expression of OGA. 28263870 2 11 theme budding 347:353 arg1 yeast 355:359 the budding yeast 343:359 the budding yeast Saccharomyces cerevisiae 343:384 Although O-GlcNAc modification widely occurs in eukaryotic cells, the budding yeast Saccharomyces cerevisiae notably lacks this protein modification and the genes for the GlcNAc transferase and hydrolase. 28263870 6 12 theme sugar 1095:1099 arg1 modifications 1101:1113 these sugar modifications 1089:1113 these sugar modifications 1089:1113 The direct analysis of yeast proteins demonstrates protein O-GlcNAcylation is dependent on sOGT expression; conversely, the hydrolysis of these sugar modifications is induced by co-expression of OGA. 28263870 10 13 theme yeast 1580:1584 arg1 cells 1586:1590 yeast cells 1580:1590 yeast cells 1580:1590 CONCLUSIONS O-GlcNAc cycling can occur in yeast cells, and OGT and OGA activities can be monitored via yeast growth. 28263870 3 14 theme OGT 496:498 arg1 isoforms 500:507 Human OGT isoforms 490:507 Human OGT isoforms 490:507 METHODS Human OGT isoforms and OGA were ectopically expressed in S. cerevisiae, and the effects of their expressions on yeast growth and O-GlcNAc modification levels were assessed. 28263870 4 15 theme sugars 832:837 arg1 hydrolysis 812:821 the hydrolysis 808:821 the hydrolysis of these sugars 808:837 RESULTS Expression of sOGT, in S. cerevisiae catalyzes the O-GlcNAc modification of proteins in vivo; conversely, the expression of OGA mediates the hydrolysis of these sugars. 28263870 5 16 from defect 879:884 arg1 cells 895:899 yeast cells 889:899 yeast cells 889:899 sOGT expression causes a severe growth defect in yeast cells, which is remediated by the co-expression of OGA. 28263870 9 17 theme transferase 1516:1526 arg1 activity 1528:1535 the O-GlcNAc transferase activity 1503:1535 the TPR domain rather than the O-GlcNAc transferase activity 1476:1535 However, its toxicity is largely attributed to the TPR domain rather than the O-GlcNAc transferase activity. 28263870 4 18 from Expression 671:680 arg1 cerevisiae 697:706 S. cerevisiae 694:706 S. cerevisiae 694:706 RESULTS Expression of sOGT, in S. cerevisiae catalyzes the O-GlcNAc modification of proteins in vivo; conversely, the expression of OGA mediates the hydrolysis of these sugars. 28263870 4 19 theme RESULTS 663:669 arg1 Expression 671:680 RESULTS Expression 663:680 RESULTS Expression 663:680 RESULTS Expression of sOGT, in S. cerevisiae catalyzes the O-GlcNAc modification of proteins in vivo; conversely, the expression of OGA mediates the hydrolysis of these sugars. 28263870 6 20 theme direct 955:960 arg1 analysis 962:969 The direct analysis 951:969 The direct analysis of yeast proteins 951:987 The direct analysis of yeast proteins demonstrates protein O-GlcNAcylation is dependent on sOGT expression; conversely, the hydrolysis of these sugar modifications is induced by co-expression of OGA. 28263870 4 21 theme OGA 795:797 arg1 expression 781:790 the expression 777:790 the expression of OGA 777:797 RESULTS Expression of sOGT, in S. cerevisiae catalyzes the O-GlcNAc modification of proteins in vivo; conversely, the expression of OGA mediates the hydrolysis of these sugars. 28263870 2 22 dep yeast 355:359 arg1 cerevisiae 375:384 Saccharomyces cerevisiae 361:384 the budding yeast Saccharomyces cerevisiae 343:384 Although O-GlcNAc modification widely occurs in eukaryotic cells, the budding yeast Saccharomyces cerevisiae notably lacks this protein modification and the genes for the GlcNAc transferase and hydrolase. 28263870 10 23 theme CONCLUSIONS 1538:1548 arg1 cycling 1559:1565 CONCLUSIONS O-GlcNAc cycling 1538:1565 CONCLUSIONS O-GlcNAc cycling 1538:1565 CONCLUSIONS O-GlcNAc cycling can occur in yeast cells, and OGT and OGA activities can be monitored via yeast growth. 28263870 2 24 theme GlcNAc 448:453 arg1 transferase 455:465 GlcNAc transferase 448:465 GlcNAc transferase 448:465 Although O-GlcNAc modification widely occurs in eukaryotic cells, the budding yeast Saccharomyces cerevisiae notably lacks this protein modification and the genes for the GlcNAc transferase and hydrolase. 28263870 10 25 theme O-GlcNAc 1550:1557 arg1 cycling 1559:1565 CONCLUSIONS O-GlcNAc cycling 1538:1565 CONCLUSIONS O-GlcNAc cycling 1538:1565 CONCLUSIONS O-GlcNAc cycling can occur in yeast cells, and OGT and OGA activities can be monitored via yeast growth. 28263870 1 26 theme BACKGROUND 66:75 arg1 O-GlcNAcylation 77:91 BACKGROUND O-GlcNAcylation 66:91 BACKGROUND O-GlcNAcylation 66:91 BACKGROUND O-GlcNAcylation is a reversible protein post-translational modification, where O-GlcNAc moiety is attached to nucleocytoplasmic protein by O-GlcNAc transferase (OGT) and removed by O-GlcNAcase (OGA). 28263870 1 26 theme BACKGROUND 66:75 arg1 modification 136:147 a reversible protein post-translational modification 96:147 a reversible protein post-translational modification 96:147 BACKGROUND O-GlcNAcylation is a reversible protein post-translational modification, where O-GlcNAc moiety is attached to nucleocytoplasmic protein by O-GlcNAc transferase (OGT) and removed by O-GlcNAcase (OGA). 28263870 10 27 theme OGA 1605:1607 arg1 activities 1609:1618 OGT and OGA activities 1597:1618 OGT and OGA activities 1597:1618 CONCLUSIONS O-GlcNAc cycling can occur in yeast cells, and OGT and OGA activities can be monitored via yeast growth. 28263870 0 28 theme Yeast 0:4 arg1 cells 6:10 Yeast cells 0:10 Yeast cells 0:10 Yeast cells as an assay system for in vivo O-GlcNAc modification. 28263870 8 29 theme OGT 1361:1363 arg1 isoform 1365:1371 another OGT isoform 1353:1371 another OGT isoform 1353:1371 Expression of another OGT isoform, ncOGT, also results in a growth defect in yeast cells. 28263870 8 29 theme OGT 1361:1363 arg1 ncOGT 1374:1378 ncOGT 1374:1378 ncOGT 1374:1378 Expression of another OGT isoform, ncOGT, also results in a growth defect in yeast cells. 28263870 1 30 theme nucleocytoplasmic 187:203 arg1 protein 205:211 nucleocytoplasmic protein 187:211 nucleocytoplasmic protein by O-GlcNAc transferase (OGT) 187:241 BACKGROUND O-GlcNAcylation is a reversible protein post-translational modification, where O-GlcNAc moiety is attached to nucleocytoplasmic protein by O-GlcNAc transferase (OGT) and removed by O-GlcNAcase (OGA). 28263870 3 31 theme yeast 602:606 arg1 growth 608:613 yeast growth 602:613 yeast growth 602:613 METHODS Human OGT isoforms and OGA were ectopically expressed in S. cerevisiae, and the effects of their expressions on yeast growth and O-GlcNAc modification levels were assessed. 28263870 3 32 theme expressions 587:597 arg1 effects 570:576 the effects 566:576 the effects of their expressions on yeast growth and O-GlcNAc modification levels 566:646 METHODS Human OGT isoforms and OGA were ectopically expressed in S. cerevisiae, and the effects of their expressions on yeast growth and O-GlcNAc modification levels were assessed. 28263870 6 33 theme sOGT 1042:1045 arg1 expression 1047:1056 sOGT expression 1042:1056 sOGT expression 1042:1056 The direct analysis of yeast proteins demonstrates protein O-GlcNAcylation is dependent on sOGT expression; conversely, the hydrolysis of these sugar modifications is induced by co-expression of OGA. 28263870 7 34 theme Protein 1151:1157 arg1 O-GlcNAcylation 1159:1173 Protein O-GlcNAcylation 1151:1173 Protein O-GlcNAcylation 1151:1173 Protein O-GlcNAcylation and the growth defects of yeast cells are caused by the O-GlcNAc transferase activity because catalytically inactive sOGT does not exhibit toxicity in yeast cells. 28263870 11 35 used used 1695:1698 arg2 cells 1682:1686 GENERAL SIGNIFICANCE Yeast cells 1655:1686 GENERAL SIGNIFICANCE Yeast cells 1655:1686 GENERAL SIGNIFICANCE Yeast cells may be used to assess OGT and OGA. 28263870 1 36 attach attached 175:182 arg2 moiety 165:170 O-GlcNAc moiety 156:170 O-GlcNAc moiety 156:170 BACKGROUND O-GlcNAcylation is a reversible protein post-translational modification, where O-GlcNAc moiety is attached to nucleocytoplasmic protein by O-GlcNAc transferase (OGT) and removed by O-GlcNAcase (OGA). 28263870 1 36 attach attached 175:182 arg1 protein 205:211 nucleocytoplasmic protein 187:211 nucleocytoplasmic protein by O-GlcNAc transferase (OGT) 187:241 BACKGROUND O-GlcNAcylation is a reversible protein post-translational modification, where O-GlcNAc moiety is attached to nucleocytoplasmic protein by O-GlcNAc transferase (OGT) and removed by O-GlcNAcase (OGA). 28263870 2 37 theme O-GlcNAc 286:293 arg1 modification 295:306 O-GlcNAc modification 286:306 O-GlcNAc modification 286:306 Although O-GlcNAc modification widely occurs in eukaryotic cells, the budding yeast Saccharomyces cerevisiae notably lacks this protein modification and the genes for the GlcNAc transferase and hydrolase. 28263870 7 38 theme O-GlcNAc 1231:1238 arg1 activity 1252:1259 the O-GlcNAc transferase activity 1227:1259 the O-GlcNAc transferase activity 1227:1259 Protein O-GlcNAcylation and the growth defects of yeast cells are caused by the O-GlcNAc transferase activity because catalytically inactive sOGT does not exhibit toxicity in yeast cells. 28263870 10 39 theme OGT 1597:1599 arg1 activities 1609:1618 OGT and OGA activities 1597:1618 OGT and OGA activities 1597:1618 CONCLUSIONS O-GlcNAc cycling can occur in yeast cells, and OGT and OGA activities can be monitored via yeast growth. 28263870 7 40 theme inactive 1283:1290 arg1 sOGT 1292:1295 catalytically inactive sOGT 1269:1295 catalytically inactive sOGT 1269:1295 Protein O-GlcNAcylation and the growth defects of yeast cells are caused by the O-GlcNAc transferase activity because catalytically inactive sOGT does not exhibit toxicity in yeast cells. 28263870 10 41 theme yeast 1641:1645 arg1 growth 1647:1652 yeast growth 1641:1652 yeast growth 1641:1652 CONCLUSIONS O-GlcNAc cycling can occur in yeast cells, and OGT and OGA activities can be monitored via yeast growth. 28263870 8 42 theme yeast 1416:1420 arg1 cells 1422:1426 yeast cells 1416:1426 yeast cells 1416:1426 Expression of another OGT isoform, ncOGT, also results in a growth defect in yeast cells. 28263870 0 43 dep in 35:36 arg1 vivo 38:41 vivo 38:41 vivo 38:41 Yeast cells as an assay system for in vivo O-GlcNAc modification. 28263870 5 44 theme severe 865:870 arg1 defect 879:884 a severe growth defect 863:884 a severe growth defect 863:884 sOGT expression causes a severe growth defect in yeast cells, which is remediated by the co-expression of OGA. 28263870 1 45 theme O-GlcNAc 216:223 arg1 OGT 238:240 OGT 238:240 OGT 238:240 BACKGROUND O-GlcNAcylation is a reversible protein post-translational modification, where O-GlcNAc moiety is attached to nucleocytoplasmic protein by O-GlcNAc transferase (OGT) and removed by O-GlcNAcase (OGA). 28263870 1 45 theme O-GlcNAc 216:223 arg1 transferase 225:235 O-GlcNAc transferase 216:235 O-GlcNAc transferase (OGT) 216:241 BACKGROUND O-GlcNAcylation is a reversible protein post-translational modification, where O-GlcNAc moiety is attached to nucleocytoplasmic protein by O-GlcNAc transferase (OGT) and removed by O-GlcNAcase (OGA). 28263870 0 46 theme assay 18:22 arg1 system 24:29 an assay system 15:29 an assay system for in vivo O-GlcNAc modification 15:63 Yeast cells as an assay system for in vivo O-GlcNAc modification. 28263870 3 47 theme modification 628:639 arg1 levels 641:646 yeast growth and O-GlcNAc modification levels 602:646 yeast growth and O-GlcNAc modification levels 602:646 METHODS Human OGT isoforms and OGA were ectopically expressed in S. cerevisiae, and the effects of their expressions on yeast growth and O-GlcNAc modification levels were assessed. 28263870 2 48 theme protein 405:411 arg1 modification 413:424 this protein modification 400:424 this protein modification 400:424 Although O-GlcNAc modification widely occurs in eukaryotic cells, the budding yeast Saccharomyces cerevisiae notably lacks this protein modification and the genes for the GlcNAc transferase and hydrolase. 28263870 0 49 theme in 35:36 arg1 modification 52:63 in vivo O-GlcNAc modification 35:63 in vivo O-GlcNAc modification 35:63 Yeast cells as an assay system for in vivo O-GlcNAc modification. 28263870 8 50 theme isoform 1365:1371 arg1 Expression 1339:1348 Expression 1339:1348 Expression of another OGT isoform, ncOGT, 1339:1379 Expression of another OGT isoform, ncOGT, also results in a growth defect in yeast cells. 28263870 6 51 theme modifications 1101:1113 arg1 hydrolysis 1075:1084 the hydrolysis 1071:1084 the hydrolysis of these sugar modifications 1071:1113 The direct analysis of yeast proteins demonstrates protein O-GlcNAcylation is dependent on sOGT expression; conversely, the hydrolysis of these sugar modifications is induced by co-expression of OGA. 28263870 1 52 theme reversible 98:107 arg1 O-GlcNAcylation 77:91 BACKGROUND O-GlcNAcylation 66:91 BACKGROUND O-GlcNAcylation 66:91 BACKGROUND O-GlcNAcylation is a reversible protein post-translational modification, where O-GlcNAc moiety is attached to nucleocytoplasmic protein by O-GlcNAc transferase (OGT) and removed by O-GlcNAcase (OGA). 28263870 1 52 theme reversible 98:107 arg1 modification 136:147 a reversible protein post-translational modification 96:147 a reversible protein post-translational modification 96:147 BACKGROUND O-GlcNAcylation is a reversible protein post-translational modification, where O-GlcNAc moiety is attached to nucleocytoplasmic protein by O-GlcNAc transferase (OGT) and removed by O-GlcNAcase (OGA). 28263870 7 53 theme growth 1183:1188 arg1 defects 1190:1196 the growth defects 1179:1196 the growth defects of yeast cells 1179:1211 Protein O-GlcNAcylation and the growth defects of yeast cells are caused by the O-GlcNAc transferase activity because catalytically inactive sOGT does not exhibit toxicity in yeast cells. 28263870 1 54 theme protein 109:115 arg1 O-GlcNAcylation 77:91 BACKGROUND O-GlcNAcylation 66:91 BACKGROUND O-GlcNAcylation 66:91 BACKGROUND O-GlcNAcylation is a reversible protein post-translational modification, where O-GlcNAc moiety is attached to nucleocytoplasmic protein by O-GlcNAc transferase (OGT) and removed by O-GlcNAcase (OGA). 28263870 1 54 theme protein 109:115 arg1 modification 136:147 a reversible protein post-translational modification 96:147 a reversible protein post-translational modification 96:147 BACKGROUND O-GlcNAcylation is a reversible protein post-translational modification, where O-GlcNAc moiety is attached to nucleocytoplasmic protein by O-GlcNAc transferase (OGT) and removed by O-GlcNAcase (OGA). 28263870 4 55 theme O-GlcNAc 722:729 arg1 modification 731:742 the O-GlcNAc modification 718:742 the O-GlcNAc modification of proteins 718:754 RESULTS Expression of sOGT, in S. cerevisiae catalyzes the O-GlcNAc modification of proteins in vivo; conversely, the expression of OGA mediates the hydrolysis of these sugars. 28263870 7 56 theme transferase 1240:1250 arg1 activity 1252:1259 the O-GlcNAc transferase activity 1227:1259 the O-GlcNAc transferase activity 1227:1259 Protein O-GlcNAcylation and the growth defects of yeast cells are caused by the O-GlcNAc transferase activity because catalytically inactive sOGT does not exhibit toxicity in yeast cells. 28263870 11 57 theme SIGNIFICANCE 1663:1674 arg1 cells 1682:1686 GENERAL SIGNIFICANCE Yeast cells 1655:1686 GENERAL SIGNIFICANCE Yeast cells 1655:1686 GENERAL SIGNIFICANCE Yeast cells may be used to assess OGT and OGA. 28263870 8 58 from defect 1406:1411 arg1 cells 1422:1426 yeast cells 1416:1426 yeast cells 1416:1426 Expression of another OGT isoform, ncOGT, also results in a growth defect in yeast cells. 28263870 8 59 theme growth 1399:1404 arg1 defect 1406:1411 a growth defect 1397:1411 a growth defect in yeast cells 1397:1426 Expression of another OGT isoform, ncOGT, also results in a growth defect in yeast cells. 28263870 6 60 theme protein 1002:1008 arg1 O-GlcNAcylation 1010:1024 protein O-GlcNAcylation 1002:1024 protein O-GlcNAcylation 1002:1024 The direct analysis of yeast proteins demonstrates protein O-GlcNAcylation is dependent on sOGT expression; conversely, the hydrolysis of these sugar modifications is induced by co-expression of OGA. 28263870 1 61 theme post-translational 117:134 arg1 O-GlcNAcylation 77:91 BACKGROUND O-GlcNAcylation 66:91 BACKGROUND O-GlcNAcylation 66:91 BACKGROUND O-GlcNAcylation is a reversible protein post-translational modification, where O-GlcNAc moiety is attached to nucleocytoplasmic protein by O-GlcNAc transferase (OGT) and removed by O-GlcNAcase (OGA). 28263870 1 61 theme post-translational 117:134 arg1 modification 136:147 a reversible protein post-translational modification 96:147 a reversible protein post-translational modification 96:147 BACKGROUND O-GlcNAcylation is a reversible protein post-translational modification, where O-GlcNAc moiety is attached to nucleocytoplasmic protein by O-GlcNAc transferase (OGT) and removed by O-GlcNAcase (OGA). 28263870 11 62 theme Yeast 1676:1680 arg1 cells 1682:1686 GENERAL SIGNIFICANCE Yeast cells 1655:1686 GENERAL SIGNIFICANCE Yeast cells 1655:1686 GENERAL SIGNIFICANCE Yeast cells may be used to assess OGT and OGA. 28263870 3 63 theme O-GlcNAc 619:626 arg1 modification 628:639 O-GlcNAc modification 619:639 O-GlcNAc modification 619:639 METHODS Human OGT isoforms and OGA were ectopically expressed in S. cerevisiae, and the effects of their expressions on yeast growth and O-GlcNAc modification levels were assessed. 28263870 7 64 from toxicity 1314:1321 arg1 cells 1332:1336 yeast cells 1326:1336 yeast cells 1326:1336 Protein O-GlcNAcylation and the growth defects of yeast cells are caused by the O-GlcNAc transferase activity because catalytically inactive sOGT does not exhibit toxicity in yeast cells. 28263870 3 65 theme Human 490:494 arg1 isoforms 500:507 Human OGT isoforms 490:507 Human OGT isoforms 490:507 METHODS Human OGT isoforms and OGA were ectopically expressed in S. cerevisiae, and the effects of their expressions on yeast growth and O-GlcNAc modification levels were assessed. 28263870 2 66 theme eukaryotic 325:334 arg1 cells 336:340 eukaryotic cells 325:340 eukaryotic cells 325:340 Although O-GlcNAc modification widely occurs in eukaryotic cells, the budding yeast Saccharomyces cerevisiae notably lacks this protein modification and the genes for the GlcNAc transferase and hydrolase. 28263870 0 67 theme O-GlcNAc 43:50 arg1 modification 52:63 in vivo O-GlcNAc modification 35:63 in vivo O-GlcNAc modification 35:63 Yeast cells as an assay system for in vivo O-GlcNAc modification. 28263870 5 68 theme sOGT 840:843 arg1 expression 845:854 sOGT expression 840:854 sOGT expression 840:854 sOGT expression causes a severe growth defect in yeast cells, which is remediated by the co-expression of OGA. 28263870 0 69 dep cells 6:10 arg1 system 24:29 an assay system 15:29 an assay system for in vivo O-GlcNAc modification 15:63 Yeast cells as an assay system for in vivo O-GlcNAc modification. 28263870 9 70 theme TPR 1480:1482 arg1 domain 1484:1489 the TPR domain 1476:1489 the TPR domain rather than the O-GlcNAc transferase activity 1476:1535 However, its toxicity is largely attributed to the TPR domain rather than the O-GlcNAc transferase activity. 28263870 5 71 theme growth 872:877 arg1 defect 879:884 a severe growth defect 863:884 a severe growth defect 863:884 sOGT expression causes a severe growth defect in yeast cells, which is remediated by the co-expression of OGA. 28263870 3 72 from effects 570:576 arg1 levels 641:646 yeast growth and O-GlcNAc modification levels 602:646 yeast growth and O-GlcNAc modification levels 602:646 METHODS Human OGT isoforms and OGA were ectopically expressed in S. cerevisiae, and the effects of their expressions on yeast growth and O-GlcNAc modification levels were assessed. 28263870 9 73 theme O-GlcNAc 1507:1514 arg1 activity 1528:1535 the O-GlcNAc transferase activity 1503:1535 the TPR domain rather than the O-GlcNAc transferase activity 1476:1535 However, its toxicity is largely attributed to the TPR domain rather than the O-GlcNAc transferase activity. 28263870 3 74 theme growth 608:613 arg1 levels 641:646 yeast growth and O-GlcNAc modification levels 602:646 yeast growth and O-GlcNAc modification levels 602:646 METHODS Human OGT isoforms and OGA were ectopically expressed in S. cerevisiae, and the effects of their expressions on yeast growth and O-GlcNAc modification levels were assessed. 28263870 4 75 theme sOGT 685:688 arg1 Expression 671:680 RESULTS Expression 663:680 RESULTS Expression 663:680 RESULTS Expression of sOGT, in S. cerevisiae catalyzes the O-GlcNAc modification of proteins in vivo; conversely, the expression of OGA mediates the hydrolysis of these sugars. 28263870 6 76 theme proteins 980:987 arg1 analysis 962:969 The direct analysis 951:969 The direct analysis of yeast proteins 951:987 The direct analysis of yeast proteins demonstrates protein O-GlcNAcylation is dependent on sOGT expression; conversely, the hydrolysis of these sugar modifications is induced by co-expression of OGA. 28469711 7 0 theme similar 1210:1216 arg1 rate 1225:1228 a similar growth rate 1208:1228 a similar growth rate 1208:1228 Compared to wild-type, the ∆cpsD mutant showed a similar growth rate. 28469711 10 1 theme negative 1496:1503 arg1 staining 1505:1512 negative staining 1496:1512 negative staining in light and electron microscopy 1496:1545 Comparison of the morphology of B. longum 105-A wild-type and ∆cpsD by negative staining in light and electron microscopy revealed that the formation of fimbriae is drastically enhanced in the ∆cpsD mutant while the B. longum 105-A wild-type was coated by a thick capsule. 28469711 9 2 theme altered 1368:1374 arg1 composition 1391:1401 altered monosaccharide composition 1368:1401 altered monosaccharide composition 1368:1401 EPS was secreted by the ∆cpsD mutant, but had altered monosaccharide composition and molecular weight. 28469711 12 3 theme gastric 1927:1933 arg1 environments 1948:1959 gastric and duodenal environments 1927:1959 gastric and duodenal environments 1927:1959 The wild-type showed low pH tolerance, adaptation, and bile salt tolerance, but the ∆cpsD mutant had lost this survivability in gastric and duodenal environments. 28469711 4 4 theme CPS/EPS 878:884 arg1 machinery 896:904 4 CPS/EPS synthesis machinery 876:904 4 CPS/EPS synthesis machinery proteins 876:913 RESULTS A putative B. longum 105-A CPS/EPS gene cluster was shown to consist of 24 putative genes encoding a priming glycosyltransferase (cpsD), 7 glycosyltransferases, 4 CPS/EPS synthesis machinery proteins, and 3 dTDP-L-rhamnose synthesis enzymes. 28469711 1 5 theme distinct 290:297 arg1 roles 299:303 distinct roles 290:303 distinct roles 290:303 BACKGROUND Bifidobacterium longum 105-A produces markedly high amounts of capsular polysaccharides (CPS) and exopolysaccharides (EPS) that should play distinct roles in bacterial-host interactions. 28469711 12 6 theme duodenal 1939:1946 arg1 environments 1948:1959 gastric and duodenal environments 1927:1959 gastric and duodenal environments 1927:1959 The wild-type showed low pH tolerance, adaptation, and bile salt tolerance, but the ∆cpsD mutant had lost this survivability in gastric and duodenal environments. 28469711 9 7 theme molecular 1407:1415 arg1 weight 1417:1422 molecular weight 1407:1422 molecular weight 1407:1422 EPS was secreted by the ∆cpsD mutant, but had altered monosaccharide composition and molecular weight. 28469711 6 8 theme cross-over 1124:1133 arg1 recombination 1146:1158 a double cross-over homologous recombination 1115:1158 a double cross-over homologous recombination 1115:1158 To confirm this, we constructed a knockout mutant (ΔcpsD) by a double cross-over homologous recombination. 28469711 3 9 theme CPS/EPS 580:586 arg1 role 572:575 The role 568:575 The role of CPS/EPS in the adaptation to gut tract environment and bacteria-gut cell interactions 568:664 The role of CPS/EPS in the adaptation to gut tract environment and bacteria-gut cell interactions was investigated using the ΔcpsD mutant. 28469711 1 10 theme polysaccharides 222:236 arg1 EPS 268:270 EPS 268:270 EPS 268:270 BACKGROUND Bifidobacterium longum 105-A produces markedly high amounts of capsular polysaccharides (CPS) and exopolysaccharides (EPS) that should play distinct roles in bacterial-host interactions. 28469711 1 10 theme polysaccharides 222:236 arg1 CPS 239:241 CPS 239:241 CPS 239:241 BACKGROUND Bifidobacterium longum 105-A produces markedly high amounts of capsular polysaccharides (CPS) and exopolysaccharides (EPS) that should play distinct roles in bacterial-host interactions. 28469711 1 10 theme polysaccharides 222:236 arg1 amounts 202:208 high amounts 197:208 high amounts of capsular polysaccharides (CPS) and exopolysaccharides (EPS) that should play distinct roles in bacterial-host interactions 197:334 BACKGROUND Bifidobacterium longum 105-A produces markedly high amounts of capsular polysaccharides (CPS) and exopolysaccharides (EPS) that should play distinct roles in bacterial-host interactions. 28469711 1 10 theme polysaccharides 222:236 arg1 polysaccharides 222:236 capsular polysaccharides 213:236 capsular polysaccharides (CPS) 213:242 BACKGROUND Bifidobacterium longum 105-A produces markedly high amounts of capsular polysaccharides (CPS) and exopolysaccharides (EPS) that should play distinct roles in bacterial-host interactions. 28469711 1 10 theme polysaccharides 222:236 arg1 exopolysaccharides 248:265 exopolysaccharides 248:265 exopolysaccharides (EPS) 248:271 BACKGROUND Bifidobacterium longum 105-A produces markedly high amounts of capsular polysaccharides (CPS) and exopolysaccharides (EPS) that should play distinct roles in bacterial-host interactions. 28469711 13 11 theme cell 2044:2047 arg1 line 2049:2052 the human colon carcinoma Caco-2 cell line 2011:2052 the human colon carcinoma Caco-2 cell line 2011:2052 The ∆cpsD mutant was extensively able to bind to the human colon carcinoma Caco-2 cell line and was phagocytosed by murine macrophage RAW 264.7, whereas the wild-type did not bind to epithelial cells and totally resisted internalization by macrophages. 28469711 4 12 theme putative 717:724 arg1 cluster 755:761 A putative B. longum 105-A CPS/EPS gene cluster 715:761 A putative B. longum 105-A CPS/EPS gene cluster 715:761 RESULTS A putative B. longum 105-A CPS/EPS gene cluster was shown to consist of 24 putative genes encoding a priming glycosyltransferase (cpsD), 7 glycosyltransferases, 4 CPS/EPS synthesis machinery proteins, and 3 dTDP-L-rhamnose synthesis enzymes. 28469711 4 13 theme synthesis 938:946 arg1 enzymes 948:954 3 dTDP-L-rhamnose synthesis enzymes 920:954 3 dTDP-L-rhamnose synthesis enzymes 920:954 RESULTS A putative B. longum 105-A CPS/EPS gene cluster was shown to consist of 24 putative genes encoding a priming glycosyltransferase (cpsD), 7 glycosyltransferases, 4 CPS/EPS synthesis machinery proteins, and 3 dTDP-L-rhamnose synthesis enzymes. 28469711 4 13 theme synthesis 938:946 arg1 glycosyltransferase 824:842 a priming glycosyltransferase 814:842 a priming glycosyltransferase (cpsD) 814:849 RESULTS A putative B. longum 105-A CPS/EPS gene cluster was shown to consist of 24 putative genes encoding a priming glycosyltransferase (cpsD), 7 glycosyltransferases, 4 CPS/EPS synthesis machinery proteins, and 3 dTDP-L-rhamnose synthesis enzymes. 28469711 13 14 theme human 2015:2019 arg1 line 2049:2052 the human colon carcinoma Caco-2 cell line 2011:2052 the human colon carcinoma Caco-2 cell line 2011:2052 The ∆cpsD mutant was extensively able to bind to the human colon carcinoma Caco-2 cell line and was phagocytosed by murine macrophage RAW 264.7, whereas the wild-type did not bind to epithelial cells and totally resisted internalization by macrophages. 28469711 4 15 theme machinery 896:904 arg1 proteins 906:913 4 CPS/EPS synthesis machinery proteins 876:913 4 CPS/EPS synthesis machinery proteins 876:913 RESULTS A putative B. longum 105-A CPS/EPS gene cluster was shown to consist of 24 putative genes encoding a priming glycosyltransferase (cpsD), 7 glycosyltransferases, 4 CPS/EPS synthesis machinery proteins, and 3 dTDP-L-rhamnose synthesis enzymes. 28469711 4 15 theme machinery 896:904 arg1 glycosyltransferase 824:842 a priming glycosyltransferase 814:842 a priming glycosyltransferase (cpsD) 814:849 RESULTS A putative B. longum 105-A CPS/EPS gene cluster was shown to consist of 24 putative genes encoding a priming glycosyltransferase (cpsD), 7 glycosyltransferases, 4 CPS/EPS synthesis machinery proteins, and 3 dTDP-L-rhamnose synthesis enzymes. 28469711 14 16 from colonization 2372:2383 arg1 gut 2411:2413 the gut 2407:2413 the gut 2407:2413 CONCLUSIONS Our results suggest that CPS/EPS production and fimbriae formation are negatively correlated and play key roles in the survival, attachment, and colonization of B. longum 105-A in the gut. 28469711 4 17 theme B. 726:727 arg1 cluster 755:761 A putative B. longum 105-A CPS/EPS gene cluster 715:761 A putative B. longum 105-A CPS/EPS gene cluster 715:761 RESULTS A putative B. longum 105-A CPS/EPS gene cluster was shown to consist of 24 putative genes encoding a priming glycosyltransferase (cpsD), 7 glycosyltransferases, 4 CPS/EPS synthesis machinery proteins, and 3 dTDP-L-rhamnose synthesis enzymes. 28469711 10 18 theme fimbriae 1578:1585 arg1 formation 1565:1573 the formation 1561:1573 the formation of fimbriae 1561:1585 Comparison of the morphology of B. longum 105-A wild-type and ∆cpsD by negative staining in light and electron microscopy revealed that the formation of fimbriae is drastically enhanced in the ∆cpsD mutant while the B. longum 105-A wild-type was coated by a thick capsule. 28469711 5 19 theme CPS 1038:1040 arg1 biogenesis 1024:1033 the biogenesis 1020:1033 the biogenesis of CPS and/or EPS 1020:1051 These enzymes should form a complex system that is involved in the biogenesis of CPS and/or EPS. 28469711 1 20 theme BACKGROUND 139:148 arg1 105-A 173:177 BACKGROUND Bifidobacterium longum 105-A 139:177 BACKGROUND Bifidobacterium longum 105-A 139:177 BACKGROUND Bifidobacterium longum 105-A produces markedly high amounts of capsular polysaccharides (CPS) and exopolysaccharides (EPS) that should play distinct roles in bacterial-host interactions. 28469711 14 21 dep survival 2346:2353 arg1 the 2342:2344 the 2342:2344 the 2342:2344 CONCLUSIONS Our results suggest that CPS/EPS production and fimbriae formation are negatively correlated and play key roles in the survival, attachment, and colonization of B. longum 105-A in the gut. 28469711 4 22 theme 105-A 736:740 arg1 cluster 755:761 A putative B. longum 105-A CPS/EPS gene cluster 715:761 A putative B. longum 105-A CPS/EPS gene cluster 715:761 RESULTS A putative B. longum 105-A CPS/EPS gene cluster was shown to consist of 24 putative genes encoding a priming glycosyltransferase (cpsD), 7 glycosyltransferases, 4 CPS/EPS synthesis machinery proteins, and 3 dTDP-L-rhamnose synthesis enzymes. 28469711 3 23 from role 572:575 arg1 adaptation 595:604 the adaptation 591:604 the adaptation to gut tract environment and bacteria-gut cell interactions 591:664 The role of CPS/EPS in the adaptation to gut tract environment and bacteria-gut cell interactions was investigated using the ΔcpsD mutant. 28469711 11 24 theme fimbriae 1702:1709 arg1 expression 1711:1720 The fimbriae expression 1698:1720 The fimbriae expression in the ∆cpsD 1698:1733 The fimbriae expression in the ∆cpsD was closely associated with the disappearance of the CPS layer. 28469711 5 25 theme EPS 1049:1051 arg1 biogenesis 1024:1033 the biogenesis 1020:1033 the biogenesis of CPS and/or EPS 1020:1051 These enzymes should form a complex system that is involved in the biogenesis of CPS and/or EPS. 28469711 1 26 theme longum 166:171 arg1 105-A 173:177 BACKGROUND Bifidobacterium longum 105-A 139:177 BACKGROUND Bifidobacterium longum 105-A 139:177 BACKGROUND Bifidobacterium longum 105-A produces markedly high amounts of capsular polysaccharides (CPS) and exopolysaccharides (EPS) that should play distinct roles in bacterial-host interactions. 28469711 8 27 theme cell 1289:1292 arg1 clusters 1294:1301 cell clusters 1289:1301 cell clusters 1289:1301 However, it showed quicker sedimentation and formation of cell clusters in liquid culture. 28469711 14 28 theme CPS/EPS 2252:2258 arg1 production 2260:2269 CPS/EPS production 2252:2269 CPS/EPS production 2252:2269 CONCLUSIONS Our results suggest that CPS/EPS production and fimbriae formation are negatively correlated and play key roles in the survival, attachment, and colonization of B. longum 105-A in the gut. 28469711 13 29 theme murine 2078:2083 arg1 RAW 2096:2098 murine macrophage RAW 264.7 2078:2104 murine macrophage RAW 264.7 2078:2104 The ∆cpsD mutant was extensively able to bind to the human colon carcinoma Caco-2 cell line and was phagocytosed by murine macrophage RAW 264.7, whereas the wild-type did not bind to epithelial cells and totally resisted internalization by macrophages. 28469711 3 30 theme tract 613:617 arg1 environment 619:629 gut tract environment 609:629 gut tract environment 609:629 The role of CPS/EPS in the adaptation to gut tract environment and bacteria-gut cell interactions was investigated using the ΔcpsD mutant. 28469711 13 31 theme epithelial 2145:2154 arg1 cells 2156:2160 epithelial cells 2145:2160 epithelial cells 2145:2160 The ∆cpsD mutant was extensively able to bind to the human colon carcinoma Caco-2 cell line and was phagocytosed by murine macrophage RAW 264.7, whereas the wild-type did not bind to epithelial cells and totally resisted internalization by macrophages. 28469711 0 32 theme Caco-2 93:98 arg1 cells 100:104 enterocyte-like Caco-2 cells 77:104 enterocyte-like Caco-2 cells 77:104 Capsular polysaccharide inhibits adhesion of Bifidobacterium longum 105-A to enterocyte-like Caco-2 cells and phagocytosis by macrophages. 28469711 12 33 theme bile 1854:1857 arg1 tolerance 1864:1872 bile salt tolerance 1854:1872 bile salt tolerance 1854:1872 The wild-type showed low pH tolerance, adaptation, and bile salt tolerance, but the ∆cpsD mutant had lost this survivability in gastric and duodenal environments. 28469711 1 34 theme high 197:200 arg1 EPS 268:270 EPS 268:270 EPS 268:270 BACKGROUND Bifidobacterium longum 105-A produces markedly high amounts of capsular polysaccharides (CPS) and exopolysaccharides (EPS) that should play distinct roles in bacterial-host interactions. 28469711 1 34 theme high 197:200 arg1 CPS 239:241 CPS 239:241 CPS 239:241 BACKGROUND Bifidobacterium longum 105-A produces markedly high amounts of capsular polysaccharides (CPS) and exopolysaccharides (EPS) that should play distinct roles in bacterial-host interactions. 28469711 1 34 theme high 197:200 arg1 amounts 202:208 high amounts 197:208 high amounts of capsular polysaccharides (CPS) and exopolysaccharides (EPS) that should play distinct roles in bacterial-host interactions 197:334 BACKGROUND Bifidobacterium longum 105-A produces markedly high amounts of capsular polysaccharides (CPS) and exopolysaccharides (EPS) that should play distinct roles in bacterial-host interactions. 28469711 1 34 theme high 197:200 arg1 polysaccharides 222:236 capsular polysaccharides 213:236 capsular polysaccharides (CPS) 213:242 BACKGROUND Bifidobacterium longum 105-A produces markedly high amounts of capsular polysaccharides (CPS) and exopolysaccharides (EPS) that should play distinct roles in bacterial-host interactions. 28469711 1 34 theme high 197:200 arg1 exopolysaccharides 248:265 exopolysaccharides 248:265 exopolysaccharides (EPS) 248:271 BACKGROUND Bifidobacterium longum 105-A produces markedly high amounts of capsular polysaccharides (CPS) and exopolysaccharides (EPS) that should play distinct roles in bacterial-host interactions. 28469711 4 35 dep RESULTS 707:713 arg1 shown 767:771 shown 767:771 was shown to consist of 24 putative genes encoding a priming glycosyltransferase (cpsD), 7 glycosyltransferases, 4 CPS/EPS synthesis machinery proteins, and 3 dTDP-L-rhamnose synthesis enzymes 763:954 RESULTS A putative B. longum 105-A CPS/EPS gene cluster was shown to consist of 24 putative genes encoding a priming glycosyltransferase (cpsD), 7 glycosyltransferases, 4 CPS/EPS synthesis machinery proteins, and 3 dTDP-L-rhamnose synthesis enzymes. 28469711 10 36 theme morphology 1443:1452 arg1 Comparison 1425:1434 Comparison 1425:1434 Comparison of the morphology of B. longum 105-A wild-type and ∆cpsD by negative staining in light and electron microscopy 1425:1545 Comparison of the morphology of B. longum 105-A wild-type and ∆cpsD by negative staining in light and electron microscopy revealed that the formation of fimbriae is drastically enhanced in the ∆cpsD mutant while the B. longum 105-A wild-type was coated by a thick capsule. 28469711 13 37 theme macrophage 2085:2094 arg1 RAW 2096:2098 murine macrophage RAW 264.7 2078:2104 murine macrophage RAW 264.7 2078:2104 The ∆cpsD mutant was extensively able to bind to the human colon carcinoma Caco-2 cell line and was phagocytosed by murine macrophage RAW 264.7, whereas the wild-type did not bind to epithelial cells and totally resisted internalization by macrophages. 28469711 5 38 theme complex 985:991 arg1 system 993:998 a complex system 983:998 a complex system that is involved in the biogenesis of CPS and/or EPS 983:1051 These enzymes should form a complex system that is involved in the biogenesis of CPS and/or EPS. 28469711 4 39 theme gene 750:753 arg1 cluster 755:761 A putative B. longum 105-A CPS/EPS gene cluster 715:761 A putative B. longum 105-A CPS/EPS gene cluster 715:761 RESULTS A putative B. longum 105-A CPS/EPS gene cluster was shown to consist of 24 putative genes encoding a priming glycosyltransferase (cpsD), 7 glycosyltransferases, 4 CPS/EPS synthesis machinery proteins, and 3 dTDP-L-rhamnose synthesis enzymes. 28469711 0 40 theme Capsular 0:7 arg1 polysaccharide 9:22 Capsular polysaccharide 0:22 Capsular polysaccharide 0:22 Capsular polysaccharide inhibits adhesion of Bifidobacterium longum 105-A to enterocyte-like Caco-2 cells and phagocytosis by macrophages. 28469711 2 41 theme CPS/EPS 392:398 arg1 function 364:371 the biological function 349:371 the biological function of B. longum 105-A CPS/EPS 349:398 To identify the biological function of B. longum 105-A CPS/EPS, we carried out an informatics survey of the genome and identified the EPS-encoding genetic locus of B. longum 105-A that is responsible for the production of CPS/EPS. 28469711 10 42 theme 105-A 1467:1471 arg1 wild-type 1473:1481 B. longum 105-A wild-type 1457:1481 B. longum 105-A wild-type 1457:1481 Comparison of the morphology of B. longum 105-A wild-type and ∆cpsD by negative staining in light and electron microscopy revealed that the formation of fimbriae is drastically enhanced in the ∆cpsD mutant while the B. longum 105-A wild-type was coated by a thick capsule. 28469711 2 43 dep B. 376:377 arg1 longum 379:384 longum 379:384 longum 379:384 To identify the biological function of B. longum 105-A CPS/EPS, we carried out an informatics survey of the genome and identified the EPS-encoding genetic locus of B. longum 105-A that is responsible for the production of CPS/EPS. 28469711 1 44 theme bacterial-host 308:321 arg1 interactions 323:334 bacterial-host interactions 308:334 bacterial-host interactions 308:334 BACKGROUND Bifidobacterium longum 105-A produces markedly high amounts of capsular polysaccharides (CPS) and exopolysaccharides (EPS) that should play distinct roles in bacterial-host interactions. 28469711 10 45 from staining 1505:1512 arg1 light 1517:1521 light 1517:1521 light 1517:1521 Comparison of the morphology of B. longum 105-A wild-type and ∆cpsD by negative staining in light and electron microscopy revealed that the formation of fimbriae is drastically enhanced in the ∆cpsD mutant while the B. longum 105-A wild-type was coated by a thick capsule. 28469711 10 45 from staining 1505:1512 arg1 microscopy 1536:1545 electron microscopy 1527:1545 electron microscopy 1527:1545 Comparison of the morphology of B. longum 105-A wild-type and ∆cpsD by negative staining in light and electron microscopy revealed that the formation of fimbriae is drastically enhanced in the ∆cpsD mutant while the B. longum 105-A wild-type was coated by a thick capsule. 28469711 10 46 theme B. 1457:1458 arg1 wild-type 1473:1481 B. longum 105-A wild-type 1457:1481 B. longum 105-A wild-type 1457:1481 Comparison of the morphology of B. longum 105-A wild-type and ∆cpsD by negative staining in light and electron microscopy revealed that the formation of fimbriae is drastically enhanced in the ∆cpsD mutant while the B. longum 105-A wild-type was coated by a thick capsule. 28469711 4 47 theme priming 816:822 arg1 proteins 906:913 4 CPS/EPS synthesis machinery proteins 876:913 4 CPS/EPS synthesis machinery proteins 876:913 RESULTS A putative B. longum 105-A CPS/EPS gene cluster was shown to consist of 24 putative genes encoding a priming glycosyltransferase (cpsD), 7 glycosyltransferases, 4 CPS/EPS synthesis machinery proteins, and 3 dTDP-L-rhamnose synthesis enzymes. 28469711 4 47 theme priming 816:822 arg1 cpsD 845:848 cpsD 845:848 cpsD 845:848 RESULTS A putative B. longum 105-A CPS/EPS gene cluster was shown to consist of 24 putative genes encoding a priming glycosyltransferase (cpsD), 7 glycosyltransferases, 4 CPS/EPS synthesis machinery proteins, and 3 dTDP-L-rhamnose synthesis enzymes. 28469711 4 47 theme priming 816:822 arg1 glycosyltransferase 824:842 a priming glycosyltransferase 814:842 a priming glycosyltransferase (cpsD) 814:849 RESULTS A putative B. longum 105-A CPS/EPS gene cluster was shown to consist of 24 putative genes encoding a priming glycosyltransferase (cpsD), 7 glycosyltransferases, 4 CPS/EPS synthesis machinery proteins, and 3 dTDP-L-rhamnose synthesis enzymes. 28469711 4 47 theme priming 816:822 arg1 enzymes 948:954 3 dTDP-L-rhamnose synthesis enzymes 920:954 3 dTDP-L-rhamnose synthesis enzymes 920:954 RESULTS A putative B. longum 105-A CPS/EPS gene cluster was shown to consist of 24 putative genes encoding a priming glycosyltransferase (cpsD), 7 glycosyltransferases, 4 CPS/EPS synthesis machinery proteins, and 3 dTDP-L-rhamnose synthesis enzymes. 28469711 4 47 theme priming 816:822 arg1 glycosyltransferases 854:873 7 glycosyltransferases 852:873 7 glycosyltransferases 852:873 RESULTS A putative B. longum 105-A CPS/EPS gene cluster was shown to consist of 24 putative genes encoding a priming glycosyltransferase (cpsD), 7 glycosyltransferases, 4 CPS/EPS synthesis machinery proteins, and 3 dTDP-L-rhamnose synthesis enzymes. 28469711 12 48 theme pH 1824:1825 arg1 tolerance 1827:1835 low pH tolerance 1820:1835 low pH tolerance 1820:1835 The wild-type showed low pH tolerance, adaptation, and bile salt tolerance, but the ∆cpsD mutant had lost this survivability in gastric and duodenal environments. 28469711 2 49 theme genetic 484:490 arg1 responsible 525:535 responsible 525:535 responsible 525:535 To identify the biological function of B. longum 105-A CPS/EPS, we carried out an informatics survey of the genome and identified the EPS-encoding genetic locus of B. longum 105-A that is responsible for the production of CPS/EPS. 28469711 2 49 theme genetic 484:490 arg1 locus 492:496 the EPS-encoding genetic locus 467:496 the EPS-encoding genetic locus of B. longum 105-A that is responsible for the production of CPS/EPS 467:565 To identify the biological function of B. longum 105-A CPS/EPS, we carried out an informatics survey of the genome and identified the EPS-encoding genetic locus of B. longum 105-A that is responsible for the production of CPS/EPS. 28469711 3 50 theme cell 648:651 arg1 interactions 653:664 bacteria-gut cell interactions 635:664 bacteria-gut cell interactions 635:664 The role of CPS/EPS in the adaptation to gut tract environment and bacteria-gut cell interactions was investigated using the ΔcpsD mutant. 28469711 2 51 theme B. 376:377 arg1 CPS/EPS 392:398 B. longum 105-A CPS/EPS 376:398 B. longum 105-A CPS/EPS 376:398 To identify the biological function of B. longum 105-A CPS/EPS, we carried out an informatics survey of the genome and identified the EPS-encoding genetic locus of B. longum 105-A that is responsible for the production of CPS/EPS. 28469711 0 52 theme longum 61:66 arg1 phagocytosis 110:121 phagocytosis 110:121 phagocytosis by macrophages 110:136 Capsular polysaccharide inhibits adhesion of Bifidobacterium longum 105-A to enterocyte-like Caco-2 cells and phagocytosis by macrophages. 28469711 0 52 theme longum 61:66 arg1 adhesion 33:40 adhesion 33:40 adhesion of Bifidobacterium longum 105-A to enterocyte-like Caco-2 cells 33:104 Capsular polysaccharide inhibits adhesion of Bifidobacterium longum 105-A to enterocyte-like Caco-2 cells and phagocytosis by macrophages. 28469711 2 53 dep B. 501:502 arg1 longum 504:509 longum 504:509 longum 504:509 To identify the biological function of B. longum 105-A CPS/EPS, we carried out an informatics survey of the genome and identified the EPS-encoding genetic locus of B. longum 105-A that is responsible for the production of CPS/EPS. 28469711 3 54 theme ΔcpsD 693:697 arg1 mutant 699:704 the ΔcpsD mutant 689:704 the ΔcpsD mutant 689:704 The role of CPS/EPS in the adaptation to gut tract environment and bacteria-gut cell interactions was investigated using the ΔcpsD mutant. 28469711 4 55 theme putative 790:797 arg1 genes 799:803 24 putative genes 787:803 24 putative genes encoding a priming glycosyltransferase (cpsD), 7 glycosyltransferases, 4 CPS/EPS synthesis machinery proteins, and 3 dTDP-L-rhamnose synthesis enzymes 787:954 RESULTS A putative B. longum 105-A CPS/EPS gene cluster was shown to consist of 24 putative genes encoding a priming glycosyltransferase (cpsD), 7 glycosyltransferases, 4 CPS/EPS synthesis machinery proteins, and 3 dTDP-L-rhamnose synthesis enzymes. 28469711 13 56 theme ∆cpsD 1966:1970 arg1 mutant 1972:1977 The ∆cpsD mutant 1962:1977 The ∆cpsD mutant 1962:1977 The ∆cpsD mutant was extensively able to bind to the human colon carcinoma Caco-2 cell line and was phagocytosed by murine macrophage RAW 264.7, whereas the wild-type did not bind to epithelial cells and totally resisted internalization by macrophages. 28469711 13 56 theme ∆cpsD 1966:1970 arg1 able 1995:1998 able 1995:1998 able 1995:1998 The ∆cpsD mutant was extensively able to bind to the human colon carcinoma Caco-2 cell line and was phagocytosed by murine macrophage RAW 264.7, whereas the wild-type did not bind to epithelial cells and totally resisted internalization by macrophages. 28469711 11 57 theme layer 1792:1796 arg1 disappearance 1767:1779 the disappearance 1763:1779 the disappearance of the CPS layer 1763:1796 The fimbriae expression in the ∆cpsD was closely associated with the disappearance of the CPS layer. 28469711 9 58 theme ∆cpsD 1346:1350 arg1 mutant 1352:1357 the ∆cpsD mutant 1342:1357 the ∆cpsD mutant 1342:1357 EPS was secreted by the ∆cpsD mutant, but had altered monosaccharide composition and molecular weight. 28469711 2 59 theme 105-A 386:390 arg1 CPS/EPS 392:398 B. longum 105-A CPS/EPS 376:398 B. longum 105-A CPS/EPS 376:398 To identify the biological function of B. longum 105-A CPS/EPS, we carried out an informatics survey of the genome and identified the EPS-encoding genetic locus of B. longum 105-A that is responsible for the production of CPS/EPS. 28469711 7 60 theme growth 1218:1223 arg1 rate 1225:1228 a similar growth rate 1208:1228 a similar growth rate 1208:1228 Compared to wild-type, the ∆cpsD mutant showed a similar growth rate. 28469711 14 61 theme key 2329:2331 arg1 roles 2333:2337 key roles 2329:2337 key roles 2329:2337 CONCLUSIONS Our results suggest that CPS/EPS production and fimbriae formation are negatively correlated and play key roles in the survival, attachment, and colonization of B. longum 105-A in the gut. 28469711 9 62 theme monosaccharide 1376:1389 arg1 composition 1391:1401 altered monosaccharide composition 1368:1401 altered monosaccharide composition 1368:1401 EPS was secreted by the ∆cpsD mutant, but had altered monosaccharide composition and molecular weight. 28469711 14 63 theme 105-A 2398:2402 arg1 survival 2346:2353 survival 2346:2353 survival 2346:2353 CONCLUSIONS Our results suggest that CPS/EPS production and fimbriae formation are negatively correlated and play key roles in the survival, attachment, and colonization of B. longum 105-A in the gut. 28469711 14 63 theme 105-A 2398:2402 arg1 attachment 2356:2365 attachment 2356:2365 attachment 2356:2365 CONCLUSIONS Our results suggest that CPS/EPS production and fimbriae formation are negatively correlated and play key roles in the survival, attachment, and colonization of B. longum 105-A in the gut. 28469711 14 63 theme 105-A 2398:2402 arg1 colonization 2372:2383 colonization 2372:2383 colonization 2372:2383 CONCLUSIONS Our results suggest that CPS/EPS production and fimbriae formation are negatively correlated and play key roles in the survival, attachment, and colonization of B. longum 105-A in the gut. 28469711 10 64 theme electron 1527:1534 arg1 microscopy 1536:1545 electron microscopy 1527:1545 electron microscopy 1527:1545 Comparison of the morphology of B. longum 105-A wild-type and ∆cpsD by negative staining in light and electron microscopy revealed that the formation of fimbriae is drastically enhanced in the ∆cpsD mutant while the B. longum 105-A wild-type was coated by a thick capsule. 28469711 14 65 theme B. 2388:2389 arg1 105-A 2398:2402 B. longum 105-A 2388:2402 B. longum 105-A 2388:2402 CONCLUSIONS Our results suggest that CPS/EPS production and fimbriae formation are negatively correlated and play key roles in the survival, attachment, and colonization of B. longum 105-A in the gut. 28469711 6 66 theme homologous 1135:1144 arg1 recombination 1146:1158 a double cross-over homologous recombination 1115:1158 a double cross-over homologous recombination 1115:1158 To confirm this, we constructed a knockout mutant (ΔcpsD) by a double cross-over homologous recombination. 28469711 1 67 theme capsular 213:220 arg1 CPS 239:241 CPS 239:241 CPS 239:241 BACKGROUND Bifidobacterium longum 105-A produces markedly high amounts of capsular polysaccharides (CPS) and exopolysaccharides (EPS) that should play distinct roles in bacterial-host interactions. 28469711 1 67 theme capsular 213:220 arg1 polysaccharides 222:236 capsular polysaccharides 213:236 capsular polysaccharides (CPS) 213:242 BACKGROUND Bifidobacterium longum 105-A produces markedly high amounts of capsular polysaccharides (CPS) and exopolysaccharides (EPS) that should play distinct roles in bacterial-host interactions. 28469711 6 68 theme double 1117:1122 arg1 recombination 1146:1158 a double cross-over homologous recombination 1115:1158 a double cross-over homologous recombination 1115:1158 To confirm this, we constructed a knockout mutant (ΔcpsD) by a double cross-over homologous recombination. 28469711 2 69 theme CPS/EPS 559:565 arg1 production 545:554 the production 541:554 the production of CPS/EPS 541:565 To identify the biological function of B. longum 105-A CPS/EPS, we carried out an informatics survey of the genome and identified the EPS-encoding genetic locus of B. longum 105-A that is responsible for the production of CPS/EPS. 28469711 14 70 dep CONCLUSIONS 2215:2225 arg1 suggest 2239:2245 suggest 2239:2245 suggest that CPS/EPS production and fimbriae formation are negatively correlated and play key roles in the survival, attachment, and colonization of B. longum 105-A in the gut 2239:2413 CONCLUSIONS Our results suggest that CPS/EPS production and fimbriae formation are negatively correlated and play key roles in the survival, attachment, and colonization of B. longum 105-A in the gut. 28469711 2 71 contain carried 404:410 arg1 we 401:402 we 401:402 we 401:402 To identify the biological function of B. longum 105-A CPS/EPS, we carried out an informatics survey of the genome and identified the EPS-encoding genetic locus of B. longum 105-A that is responsible for the production of CPS/EPS. 28469711 2 71 contain carried 404:410 arg2 survey 431:436 an informatics survey 416:436 an informatics survey of the genome 416:450 To identify the biological function of B. longum 105-A CPS/EPS, we carried out an informatics survey of the genome and identified the EPS-encoding genetic locus of B. longum 105-A that is responsible for the production of CPS/EPS. 28469711 4 72 theme dTDP-L-rhamnose 922:936 arg1 enzymes 948:954 3 dTDP-L-rhamnose synthesis enzymes 920:954 3 dTDP-L-rhamnose synthesis enzymes 920:954 RESULTS A putative B. longum 105-A CPS/EPS gene cluster was shown to consist of 24 putative genes encoding a priming glycosyltransferase (cpsD), 7 glycosyltransferases, 4 CPS/EPS synthesis machinery proteins, and 3 dTDP-L-rhamnose synthesis enzymes. 28469711 4 72 theme dTDP-L-rhamnose 922:936 arg1 glycosyltransferase 824:842 a priming glycosyltransferase 814:842 a priming glycosyltransferase (cpsD) 814:849 RESULTS A putative B. longum 105-A CPS/EPS gene cluster was shown to consist of 24 putative genes encoding a priming glycosyltransferase (cpsD), 7 glycosyltransferases, 4 CPS/EPS synthesis machinery proteins, and 3 dTDP-L-rhamnose synthesis enzymes. 28469711 14 73 from attachment 2356:2365 arg1 gut 2411:2413 the gut 2407:2413 the gut 2407:2413 CONCLUSIONS Our results suggest that CPS/EPS production and fimbriae formation are negatively correlated and play key roles in the survival, attachment, and colonization of B. longum 105-A in the gut. 28469711 11 74 theme CPS 1788:1790 arg1 layer 1792:1796 the CPS layer 1784:1796 the CPS layer 1784:1796 The fimbriae expression in the ∆cpsD was closely associated with the disappearance of the CPS layer. 28469711 12 75 theme ∆cpsD 1883:1887 arg1 mutant 1889:1894 the ∆cpsD mutant 1879:1894 the ∆cpsD mutant 1879:1894 The wild-type showed low pH tolerance, adaptation, and bile salt tolerance, but the ∆cpsD mutant had lost this survivability in gastric and duodenal environments. 28469711 4 76 theme synthesis 886:894 arg1 machinery 896:904 4 CPS/EPS synthesis machinery 876:904 4 CPS/EPS synthesis machinery proteins 876:913 RESULTS A putative B. longum 105-A CPS/EPS gene cluster was shown to consist of 24 putative genes encoding a priming glycosyltransferase (cpsD), 7 glycosyltransferases, 4 CPS/EPS synthesis machinery proteins, and 3 dTDP-L-rhamnose synthesis enzymes. 28469711 8 77 theme quicker 1250:1256 arg1 sedimentation 1258:1270 quicker sedimentation 1250:1270 quicker sedimentation 1250:1270 However, it showed quicker sedimentation and formation of cell clusters in liquid culture. 28469711 14 78 theme fimbriae 2275:2282 arg1 formation 2284:2292 fimbriae formation 2275:2292 fimbriae formation 2275:2292 CONCLUSIONS Our results suggest that CPS/EPS production and fimbriae formation are negatively correlated and play key roles in the survival, attachment, and colonization of B. longum 105-A in the gut. 28469711 13 79 theme colon 2021:2025 arg1 line 2049:2052 the human colon carcinoma Caco-2 cell line 2011:2052 the human colon carcinoma Caco-2 cell line 2011:2052 The ∆cpsD mutant was extensively able to bind to the human colon carcinoma Caco-2 cell line and was phagocytosed by murine macrophage RAW 264.7, whereas the wild-type did not bind to epithelial cells and totally resisted internalization by macrophages. 28469711 11 80 from expression 1711:1720 arg1 ∆cpsD 1729:1733 the ∆cpsD 1725:1733 the ∆cpsD 1725:1733 The fimbriae expression in the ∆cpsD was closely associated with the disappearance of the CPS layer. 28469711 0 81 theme enterocyte-like 77:91 arg1 cells 100:104 enterocyte-like Caco-2 cells 77:104 enterocyte-like Caco-2 cells 77:104 Capsular polysaccharide inhibits adhesion of Bifidobacterium longum 105-A to enterocyte-like Caco-2 cells and phagocytosis by macrophages. 28469711 13 82 theme Caco-2 2037:2042 arg1 line 2049:2052 the human colon carcinoma Caco-2 cell line 2011:2052 the human colon carcinoma Caco-2 cell line 2011:2052 The ∆cpsD mutant was extensively able to bind to the human colon carcinoma Caco-2 cell line and was phagocytosed by murine macrophage RAW 264.7, whereas the wild-type did not bind to epithelial cells and totally resisted internalization by macrophages. 28469711 3 83 theme gut 609:611 arg1 environment 619:629 gut tract environment 609:629 gut tract environment 609:629 The role of CPS/EPS in the adaptation to gut tract environment and bacteria-gut cell interactions was investigated using the ΔcpsD mutant. 28469711 2 84 theme 105-A 511:515 arg1 responsible 525:535 responsible 525:535 responsible 525:535 To identify the biological function of B. longum 105-A CPS/EPS, we carried out an informatics survey of the genome and identified the EPS-encoding genetic locus of B. longum 105-A that is responsible for the production of CPS/EPS. 28469711 2 84 theme 105-A 511:515 arg1 locus 492:496 the EPS-encoding genetic locus 467:496 the EPS-encoding genetic locus of B. longum 105-A that is responsible for the production of CPS/EPS 467:565 To identify the biological function of B. longum 105-A CPS/EPS, we carried out an informatics survey of the genome and identified the EPS-encoding genetic locus of B. longum 105-A that is responsible for the production of CPS/EPS. 28469711 14 85 dep B. 2388:2389 arg1 longum 2391:2396 longum 2391:2396 longum 2391:2396 CONCLUSIONS Our results suggest that CPS/EPS production and fimbriae formation are negatively correlated and play key roles in the survival, attachment, and colonization of B. longum 105-A in the gut. 28469711 14 86 from survival 2346:2353 arg1 gut 2411:2413 the gut 2407:2413 the gut 2407:2413 CONCLUSIONS Our results suggest that CPS/EPS production and fimbriae formation are negatively correlated and play key roles in the survival, attachment, and colonization of B. longum 105-A in the gut. 28469711 1 87 theme exopolysaccharides 248:265 arg1 EPS 268:270 EPS 268:270 EPS 268:270 BACKGROUND Bifidobacterium longum 105-A produces markedly high amounts of capsular polysaccharides (CPS) and exopolysaccharides (EPS) that should play distinct roles in bacterial-host interactions. 28469711 1 87 theme exopolysaccharides 248:265 arg1 CPS 239:241 CPS 239:241 CPS 239:241 BACKGROUND Bifidobacterium longum 105-A produces markedly high amounts of capsular polysaccharides (CPS) and exopolysaccharides (EPS) that should play distinct roles in bacterial-host interactions. 28469711 1 87 theme exopolysaccharides 248:265 arg1 amounts 202:208 high amounts 197:208 high amounts of capsular polysaccharides (CPS) and exopolysaccharides (EPS) that should play distinct roles in bacterial-host interactions 197:334 BACKGROUND Bifidobacterium longum 105-A produces markedly high amounts of capsular polysaccharides (CPS) and exopolysaccharides (EPS) that should play distinct roles in bacterial-host interactions. 28469711 1 87 theme exopolysaccharides 248:265 arg1 polysaccharides 222:236 capsular polysaccharides 213:236 capsular polysaccharides (CPS) 213:242 BACKGROUND Bifidobacterium longum 105-A produces markedly high amounts of capsular polysaccharides (CPS) and exopolysaccharides (EPS) that should play distinct roles in bacterial-host interactions. 28469711 1 87 theme exopolysaccharides 248:265 arg1 exopolysaccharides 248:265 exopolysaccharides 248:265 exopolysaccharides (EPS) 248:271 BACKGROUND Bifidobacterium longum 105-A produces markedly high amounts of capsular polysaccharides (CPS) and exopolysaccharides (EPS) that should play distinct roles in bacterial-host interactions. 28469711 7 88 theme ∆cpsD 1188:1192 arg1 mutant 1194:1199 the ∆cpsD mutant 1184:1199 the ∆cpsD mutant 1184:1199 Compared to wild-type, the ∆cpsD mutant showed a similar growth rate. 28469711 13 89 theme carcinoma 2027:2035 arg1 line 2049:2052 the human colon carcinoma Caco-2 cell line 2011:2052 the human colon carcinoma Caco-2 cell line 2011:2052 The ∆cpsD mutant was extensively able to bind to the human colon carcinoma Caco-2 cell line and was phagocytosed by murine macrophage RAW 264.7, whereas the wild-type did not bind to epithelial cells and totally resisted internalization by macrophages. 28469711 12 90 theme salt 1859:1862 arg1 tolerance 1864:1872 bile salt tolerance 1854:1872 bile salt tolerance 1854:1872 The wild-type showed low pH tolerance, adaptation, and bile salt tolerance, but the ∆cpsD mutant had lost this survivability in gastric and duodenal environments. 28469711 2 91 theme B. 501:502 arg1 105-A 511:515 B. longum 105-A 501:515 B. longum 105-A 501:515 To identify the biological function of B. longum 105-A CPS/EPS, we carried out an informatics survey of the genome and identified the EPS-encoding genetic locus of B. longum 105-A that is responsible for the production of CPS/EPS. 28469711 8 92 theme clusters 1294:1301 arg1 formation 1276:1284 formation 1276:1284 formation of cell clusters 1276:1301 However, it showed quicker sedimentation and formation of cell clusters in liquid culture. 28469711 8 92 theme clusters 1294:1301 arg1 sedimentation 1258:1270 quicker sedimentation 1250:1270 quicker sedimentation 1250:1270 However, it showed quicker sedimentation and formation of cell clusters in liquid culture. 28469711 10 93 dep B. 1457:1458 arg1 longum 1460:1465 longum 1460:1465 longum 1460:1465 Comparison of the morphology of B. longum 105-A wild-type and ∆cpsD by negative staining in light and electron microscopy revealed that the formation of fimbriae is drastically enhanced in the ∆cpsD mutant while the B. longum 105-A wild-type was coated by a thick capsule. 28469711 8 94 theme liquid 1306:1311 arg1 culture 1313:1319 liquid culture 1306:1319 liquid culture 1306:1319 However, it showed quicker sedimentation and formation of cell clusters in liquid culture. 28469711 10 95 theme 105-A 1651:1655 arg1 wild-type 1657:1665 the B. longum 105-A wild-type 1637:1665 the B. longum 105-A wild-type 1637:1665 Comparison of the morphology of B. longum 105-A wild-type and ∆cpsD by negative staining in light and electron microscopy revealed that the formation of fimbriae is drastically enhanced in the ∆cpsD mutant while the B. longum 105-A wild-type was coated by a thick capsule. 28469711 10 96 theme ∆cpsD 1618:1622 arg1 mutant 1624:1629 the ∆cpsD mutant 1614:1629 the ∆cpsD mutant 1614:1629 Comparison of the morphology of B. longum 105-A wild-type and ∆cpsD by negative staining in light and electron microscopy revealed that the formation of fimbriae is drastically enhanced in the ∆cpsD mutant while the B. longum 105-A wild-type was coated by a thick capsule. 28469711 4 97 theme CPS/EPS 742:748 arg1 cluster 755:761 A putative B. longum 105-A CPS/EPS gene cluster 715:761 A putative B. longum 105-A CPS/EPS gene cluster 715:761 RESULTS A putative B. longum 105-A CPS/EPS gene cluster was shown to consist of 24 putative genes encoding a priming glycosyltransferase (cpsD), 7 glycosyltransferases, 4 CPS/EPS synthesis machinery proteins, and 3 dTDP-L-rhamnose synthesis enzymes. 28469711 12 98 theme low 1820:1822 arg1 tolerance 1827:1835 low pH tolerance 1820:1835 low pH tolerance 1820:1835 The wild-type showed low pH tolerance, adaptation, and bile salt tolerance, but the ∆cpsD mutant had lost this survivability in gastric and duodenal environments. 28469711 4 99 dep B. 726:727 arg1 longum 729:734 longum 729:734 longum 729:734 RESULTS A putative B. longum 105-A CPS/EPS gene cluster was shown to consist of 24 putative genes encoding a priming glycosyltransferase (cpsD), 7 glycosyltransferases, 4 CPS/EPS synthesis machinery proteins, and 3 dTDP-L-rhamnose synthesis enzymes. 28469711 2 100 theme genome 445:450 arg1 survey 431:436 an informatics survey 416:436 an informatics survey of the genome 416:450 To identify the biological function of B. longum 105-A CPS/EPS, we carried out an informatics survey of the genome and identified the EPS-encoding genetic locus of B. longum 105-A that is responsible for the production of CPS/EPS. 28469711 10 101 theme B. 1641:1642 arg1 wild-type 1657:1665 the B. longum 105-A wild-type 1637:1665 the B. longum 105-A wild-type 1637:1665 Comparison of the morphology of B. longum 105-A wild-type and ∆cpsD by negative staining in light and electron microscopy revealed that the formation of fimbriae is drastically enhanced in the ∆cpsD mutant while the B. longum 105-A wild-type was coated by a thick capsule. 28469711 3 102 theme bacteria-gut 635:646 arg1 interactions 653:664 bacteria-gut cell interactions 635:664 bacteria-gut cell interactions 635:664 The role of CPS/EPS in the adaptation to gut tract environment and bacteria-gut cell interactions was investigated using the ΔcpsD mutant. 28469711 2 103 theme informatics 419:429 arg1 survey 431:436 an informatics survey 416:436 an informatics survey of the genome 416:450 To identify the biological function of B. longum 105-A CPS/EPS, we carried out an informatics survey of the genome and identified the EPS-encoding genetic locus of B. longum 105-A that is responsible for the production of CPS/EPS. 28469711 2 104 theme EPS-encoding 471:482 arg1 responsible 525:535 responsible 525:535 responsible 525:535 To identify the biological function of B. longum 105-A CPS/EPS, we carried out an informatics survey of the genome and identified the EPS-encoding genetic locus of B. longum 105-A that is responsible for the production of CPS/EPS. 28469711 2 104 theme EPS-encoding 471:482 arg1 locus 492:496 the EPS-encoding genetic locus 467:496 the EPS-encoding genetic locus of B. longum 105-A that is responsible for the production of CPS/EPS 467:565 To identify the biological function of B. longum 105-A CPS/EPS, we carried out an informatics survey of the genome and identified the EPS-encoding genetic locus of B. longum 105-A that is responsible for the production of CPS/EPS. 28469711 10 105 theme ∆cpsD 1487:1491 arg1 morphology 1443:1452 the morphology 1439:1452 the morphology of B. longum 105-A wild-type and ∆cpsD 1439:1491 Comparison of the morphology of B. longum 105-A wild-type and ∆cpsD by negative staining in light and electron microscopy revealed that the formation of fimbriae is drastically enhanced in the ∆cpsD mutant while the B. longum 105-A wild-type was coated by a thick capsule. 28469711 10 106 dep B. 1641:1642 arg1 longum 1644:1649 longum 1644:1649 longum 1644:1649 Comparison of the morphology of B. longum 105-A wild-type and ∆cpsD by negative staining in light and electron microscopy revealed that the formation of fimbriae is drastically enhanced in the ∆cpsD mutant while the B. longum 105-A wild-type was coated by a thick capsule. 28469711 14 107 attach attachment 2356:2365 arg2 105-A 2398:2402 B. longum 105-A 2388:2402 B. longum 105-A 2388:2402 CONCLUSIONS Our results suggest that CPS/EPS production and fimbriae formation are negatively correlated and play key roles in the survival, attachment, and colonization of B. longum 105-A in the gut. 28469711 14 107 attach attachment 2356:2365 arg3 gut 2411:2413 the gut 2407:2413 the gut 2407:2413 CONCLUSIONS Our results suggest that CPS/EPS production and fimbriae formation are negatively correlated and play key roles in the survival, attachment, and colonization of B. longum 105-A in the gut. 28469711 10 108 theme wild-type 1473:1481 arg1 morphology 1443:1452 the morphology 1439:1452 the morphology of B. longum 105-A wild-type and ∆cpsD 1439:1491 Comparison of the morphology of B. longum 105-A wild-type and ∆cpsD by negative staining in light and electron microscopy revealed that the formation of fimbriae is drastically enhanced in the ∆cpsD mutant while the B. longum 105-A wild-type was coated by a thick capsule. 28469711 2 109 theme biological 353:362 arg1 function 364:371 the biological function 349:371 the biological function of B. longum 105-A CPS/EPS 349:398 To identify the biological function of B. longum 105-A CPS/EPS, we carried out an informatics survey of the genome and identified the EPS-encoding genetic locus of B. longum 105-A that is responsible for the production of CPS/EPS. 28469711 6 110 theme knockout 1088:1095 arg1 ΔcpsD 1105:1109 ΔcpsD 1105:1109 ΔcpsD 1105:1109 To confirm this, we constructed a knockout mutant (ΔcpsD) by a double cross-over homologous recombination. 28469711 6 110 theme knockout 1088:1095 arg1 mutant 1097:1102 a knockout mutant 1086:1102 a knockout mutant (ΔcpsD) 1086:1110 To confirm this, we constructed a knockout mutant (ΔcpsD) by a double cross-over homologous recombination. 28469711 10 111 theme thick 1683:1687 arg1 capsule 1689:1695 a thick capsule 1681:1695 a thick capsule 1681:1695 Comparison of the morphology of B. longum 105-A wild-type and ∆cpsD by negative staining in light and electron microscopy revealed that the formation of fimbriae is drastically enhanced in the ∆cpsD mutant while the B. longum 105-A wild-type was coated by a thick capsule. 24850431 5 0 theme increased 741:749 arg1 susceptibility 751:764 increased susceptibility 741:764 increased susceptibility to DSS-induced colitis 741:787 Co-housing with wild-type mice leveled Prevotella contents, but failed to protect caspase-11(-/-) mice from increased susceptibility to DSS-induced colitis. 24850431 1 1 theme major 150:154 arg1 syndromes 169:177 major inflammatory syndromes 150:177 major inflammatory syndromes that affect millions of patients 150:210 Ulcerative colitis and Crohn's disease are major inflammatory syndromes that affect millions of patients. 24850431 1 1 theme major 150:154 arg1 colitis 118:124 Ulcerative colitis 107:124 Ulcerative colitis 107:124 Ulcerative colitis and Crohn's disease are major inflammatory syndromes that affect millions of patients. 24850431 1 1 theme major 150:154 arg1 disease 138:144 Crohn's disease 130:144 Crohn's disease 130:144 Ulcerative colitis and Crohn's disease are major inflammatory syndromes that affect millions of patients. 24850431 7 2 theme inflammatory 887:898 arg1 infiltration 905:916 inflammatory cell infiltration 887:916 inflammatory cell infiltration 887:916 DSS-induced tissue damage and inflammatory cell infiltration in the gut were markedly increased in caspase-11−/− mice, while release of the pyroptosis/necroptosis marker HMGB1 was abolished [Corrected]. 24850431 8 3 theme interleukin 1139:1149 arg1 IL 1152:1153 mature interleukin (IL)-1β 1132:1157 mature interleukin (IL)-1β 1132:1157 Moreover, caspase-11(-/-) mice showed normal or increased production of mature interleukin (IL)-1β and IL-18, whereas IL-1β and IL-18 secretion was blunted in animals lacking both caspases 1 and 11. 24850431 1 4 theme inflammatory 156:167 arg1 syndromes 169:177 major inflammatory syndromes 150:177 major inflammatory syndromes that affect millions of patients 150:210 Ulcerative colitis and Crohn's disease are major inflammatory syndromes that affect millions of patients. 24850431 1 4 theme inflammatory 156:167 arg1 colitis 118:124 Ulcerative colitis 107:124 Ulcerative colitis 107:124 Ulcerative colitis and Crohn's disease are major inflammatory syndromes that affect millions of patients. 24850431 1 4 theme inflammatory 156:167 arg1 disease 138:144 Crohn's disease 130:144 Crohn's disease 130:144 Ulcerative colitis and Crohn's disease are major inflammatory syndromes that affect millions of patients. 24850431 7 5 theme tissue 869:874 arg1 damage 876:881 DSS-induced tissue damage 857:881 DSS-induced tissue damage 857:881 DSS-induced tissue damage and inflammatory cell infiltration in the gut were markedly increased in caspase-11−/− mice, while release of the pyroptosis/necroptosis marker HMGB1 was abolished [Corrected]. 24850431 5 6 theme wild-type 649:657 arg1 mice 659:662 wild-type mice 649:662 wild-type mice 649:662 Co-housing with wild-type mice leveled Prevotella contents, but failed to protect caspase-11(-/-) mice from increased susceptibility to DSS-induced colitis. 24850431 4 7 theme gut 593:595 arg1 microbiota 597:606 the gut microbiota 589:606 the gut microbiota of caspase-11(-/-) mice 589:630 Notably, pro-inflammatory Prevotella species were strongly reduced in the gut microbiota of caspase-11(-/-) mice. 24850431 0 8 theme sulfate-induced 82:96 arg1 colitis 98:104 dextran sodium sulfate-induced colitis 67:104 dextran sodium sulfate-induced colitis 67:104 Caspase-11 is expressed in the colonic mucosa and protects against dextran sodium sulfate-induced colitis. 24850431 7 9 from damage 876:881 arg1 gut 925:927 the gut 921:927 the gut 921:927 DSS-induced tissue damage and inflammatory cell infiltration in the gut were markedly increased in caspase-11−/− mice, while release of the pyroptosis/necroptosis marker HMGB1 was abolished [Corrected]. 24850431 5 10 with Co-housing 633:642 arg1 mice 659:662 wild-type mice 649:662 wild-type mice 649:662 Co-housing with wild-type mice leveled Prevotella contents, but failed to protect caspase-11(-/-) mice from increased susceptibility to DSS-induced colitis. 24850431 10 11 theme DSS-induced 1426:1436 arg1 activation 1451:1460 DSS-induced inflammasome activation 1426:1460 DSS-induced inflammasome activation 1426:1460 Moreover, DSS-induced inflammasome activation relied on caspase-1, but not caspase-11. 24850431 4 12 theme -/- 622:624 arg1 mice 627:630 caspase-11(-/-) mice 611:630 caspase-11(-/-) mice 611:630 Notably, pro-inflammatory Prevotella species were strongly reduced in the gut microbiota of caspase-11(-/-) mice. 24850431 8 13 dep caspases 1240:1247 arg1 11 1255:1256 11 1255:1256 11 1255:1256 Moreover, caspase-11(-/-) mice showed normal or increased production of mature interleukin (IL)-1β and IL-18, whereas IL-1β and IL-18 secretion was blunted in animals lacking both caspases 1 and 11. 24850431 8 13 dep caspases 1240:1247 arg1 1 1249:1249 1 1249:1249 1 1249:1249 Moreover, caspase-11(-/-) mice showed normal or increased production of mature interleukin (IL)-1β and IL-18, whereas IL-1β and IL-18 secretion was blunted in animals lacking both caspases 1 and 11. 24850431 7 14 theme DSS-induced 857:867 arg1 damage 876:881 DSS-induced tissue damage 857:881 DSS-induced tissue damage 857:881 DSS-induced tissue damage and inflammatory cell infiltration in the gut were markedly increased in caspase-11−/− mice, while release of the pyroptosis/necroptosis marker HMGB1 was abolished [Corrected]. 24850431 8 15 theme IL-18 1188:1192 arg1 secretion 1194:1202 IL-18 secretion 1188:1202 IL-18 secretion 1188:1202 Moreover, caspase-11(-/-) mice showed normal or increased production of mature interleukin (IL)-1β and IL-18, whereas IL-1β and IL-18 secretion was blunted in animals lacking both caspases 1 and 11. 24850431 10 16 theme inflammasome 1438:1449 arg1 activation 1451:1460 DSS-induced inflammasome activation 1426:1460 DSS-induced inflammasome activation 1426:1460 Moreover, DSS-induced inflammasome activation relied on caspase-1, but not caspase-11. 24850431 8 17 theme normal 1098:1103 arg1 production 1118:1127 normal or increased production 1098:1127 normal or increased production of mature interleukin (IL)-1β and IL-18 1098:1167 Moreover, caspase-11(-/-) mice showed normal or increased production of mature interleukin (IL)-1β and IL-18, whereas IL-1β and IL-18 secretion was blunted in animals lacking both caspases 1 and 11. 24850431 9 18 theme DSS-induced 1395:1405 arg1 colitis 1407:1413 DSS-induced colitis 1395:1413 DSS-induced colitis 1395:1413 In conclusion, we showed that caspase-11 shapes the gut microbiota composition, and that caspase-11(-/-) mice are highly susceptible to DSS-induced colitis. 24850431 8 19 theme IL-18 1163:1167 arg1 production 1118:1127 normal or increased production 1098:1127 normal or increased production of mature interleukin (IL)-1β and IL-18 1098:1167 Moreover, caspase-11(-/-) mice showed normal or increased production of mature interleukin (IL)-1β and IL-18, whereas IL-1β and IL-18 secretion was blunted in animals lacking both caspases 1 and 11. 24850431 7 20 from infiltration 905:916 arg1 gut 925:927 the gut 921:927 the gut 921:927 DSS-induced tissue damage and inflammatory cell infiltration in the gut were markedly increased in caspase-11−/− mice, while release of the pyroptosis/necroptosis marker HMGB1 was abolished [Corrected]. 24850431 4 21 theme Prevotella 545:554 arg1 species 556:562 pro-inflammatory Prevotella species 528:562 pro-inflammatory Prevotella species 528:562 Notably, pro-inflammatory Prevotella species were strongly reduced in the gut microbiota of caspase-11(-/-) mice. 24850431 7 22 theme caspase-11−/− 956:968 arg1 mice 970:973 caspase-11−/− mice 956:973 caspase-11−/− mice 956:973 DSS-induced tissue damage and inflammatory cell infiltration in the gut were markedly increased in caspase-11−/− mice, while release of the pyroptosis/necroptosis marker HMGB1 was abolished [Corrected]. 24850431 8 23 theme IL 1152:1153 arg1 production 1118:1127 normal or increased production 1098:1127 normal or increased production of mature interleukin (IL)-1β and IL-18 1098:1167 Moreover, caspase-11(-/-) mice showed normal or increased production of mature interleukin (IL)-1β and IL-18, whereas IL-1β and IL-18 secretion was blunted in animals lacking both caspases 1 and 11. 24850431 11 24 theme other 1536:1540 arg1 mechanisms 1562:1571 other caspase-11 effector mechanisms 1536:1571 other caspase-11 effector mechanisms such as pyroptosis 1536:1590 These results suggest a role for other caspase-11 effector mechanisms such as pyroptosis in protection against intestinal inflammation. 24850431 11 24 theme other 1536:1540 arg1 pyroptosis 1581:1590 pyroptosis 1581:1590 pyroptosis 1581:1590 These results suggest a role for other caspase-11 effector mechanisms such as pyroptosis in protection against intestinal inflammation. 24850431 1 25 theme Ulcerative 107:116 arg1 colitis 118:124 Ulcerative colitis 107:124 Ulcerative colitis 107:124 Ulcerative colitis and Crohn's disease are major inflammatory syndromes that affect millions of patients. 24850431 1 25 theme Ulcerative 107:116 arg1 syndromes 169:177 major inflammatory syndromes 150:177 major inflammatory syndromes that affect millions of patients 150:210 Ulcerative colitis and Crohn's disease are major inflammatory syndromes that affect millions of patients. 24850431 1 25 theme Ulcerative 107:116 arg1 disease 138:144 Crohn's disease 130:144 Crohn's disease 130:144 Ulcerative colitis and Crohn's disease are major inflammatory syndromes that affect millions of patients. 24850431 1 26 theme patients 203:210 arg1 millions 191:198 millions 191:198 millions of patients 191:210 Ulcerative colitis and Crohn's disease are major inflammatory syndromes that affect millions of patients. 24850431 0 27 theme colonic 31:37 arg1 mucosa 39:44 the colonic mucosa 27:44 the colonic mucosa 27:44 Caspase-11 is expressed in the colonic mucosa and protects against dextran sodium sulfate-induced colitis. 24850431 9 28 theme gut 1311:1313 arg1 composition 1326:1336 the gut microbiota composition 1307:1336 the gut microbiota composition 1307:1336 In conclusion, we showed that caspase-11 shapes the gut microbiota composition, and that caspase-11(-/-) mice are highly susceptible to DSS-induced colitis. 24850431 5 29 dep mice 731:734 arg1 -/- 726:728 -/- 726:728 -/- 726:728 Co-housing with wild-type mice leveled Prevotella contents, but failed to protect caspase-11(-/-) mice from increased susceptibility to DSS-induced colitis. 24850431 2 30 theme Gram-negative 251:263 arg1 enteropathogens 265:279 Gram-negative enteropathogens 251:279 Gram-negative enteropathogens 251:279 Caspase-11 confers protection against Gram-negative enteropathogens, but its role during colitis is unknown. 24850431 5 31 theme DSS-induced 769:779 arg1 colitis 781:787 DSS-induced colitis 769:787 DSS-induced colitis 769:787 Co-housing with wild-type mice leveled Prevotella contents, but failed to protect caspase-11(-/-) mice from increased susceptibility to DSS-induced colitis. 24850431 9 32 theme microbiota 1315:1324 arg1 composition 1326:1336 the gut microbiota composition 1307:1336 the gut microbiota composition 1307:1336 In conclusion, we showed that caspase-11 shapes the gut microbiota composition, and that caspase-11(-/-) mice are highly susceptible to DSS-induced colitis. 24850431 6 33 from role 817:820 arg1 signaling 846:854 immune signaling 839:854 immune signaling 839:854 We therefore addressed the role of caspase-11 in immune signaling. 24850431 7 34 theme HMGB1 1027:1031 arg1 release 982:988 release 982:988 release of the pyroptosis/necroptosis marker HMGB1 982:1031 DSS-induced tissue damage and inflammatory cell infiltration in the gut were markedly increased in caspase-11−/− mice, while release of the pyroptosis/necroptosis marker HMGB1 was abolished [Corrected]. 24850431 4 35 theme mice 627:630 arg1 microbiota 597:606 the gut microbiota 589:606 the gut microbiota of caspase-11(-/-) mice 589:630 Notably, pro-inflammatory Prevotella species were strongly reduced in the gut microbiota of caspase-11(-/-) mice. 24850431 6 36 theme immune 839:844 arg1 signaling 846:854 immune signaling 839:854 immune signaling 839:854 We therefore addressed the role of caspase-11 in immune signaling. 24850431 3 37 theme caspase-11-deficient 404:423 arg1 mice 443:446 caspase-11-deficient (caspase-11(-/-)) mice 404:446 caspase-11-deficient (caspase-11(-/-)) mice 404:446 Here, we show that caspase-11 was constitutively expressed in the colon, and that caspase-11-deficient (caspase-11(-/-)) mice were hypersusceptible to dextran sodium sulfate (DSS)-induced colitis. 24850431 4 38 theme pro-inflammatory 528:543 arg1 species 556:562 pro-inflammatory Prevotella species 528:562 pro-inflammatory Prevotella species 528:562 Notably, pro-inflammatory Prevotella species were strongly reduced in the gut microbiota of caspase-11(-/-) mice. 24850431 5 39 theme Prevotella 672:681 arg1 contents 683:690 Prevotella contents 672:690 Prevotella contents 672:690 Co-housing with wild-type mice leveled Prevotella contents, but failed to protect caspase-11(-/-) mice from increased susceptibility to DSS-induced colitis. 24850431 7 40 theme pyroptosis/necroptosis 997:1018 arg1 HMGB1 1027:1031 the pyroptosis/necroptosis marker HMGB1 993:1031 the pyroptosis/necroptosis marker HMGB1 993:1031 DSS-induced tissue damage and inflammatory cell infiltration in the gut were markedly increased in caspase-11−/− mice, while release of the pyroptosis/necroptosis marker HMGB1 was abolished [Corrected]. 24850431 6 41 theme caspase-11 825:834 arg1 role 817:820 the role 813:820 the role of caspase-11 in immune signaling 813:854 We therefore addressed the role of caspase-11 in immune signaling. 24850431 3 42 dep mice 443:446 arg1 -/- 437:439 -/- 437:439 -/- 437:439 Here, we show that caspase-11 was constitutively expressed in the colon, and that caspase-11-deficient (caspase-11(-/-)) mice were hypersusceptible to dextran sodium sulfate (DSS)-induced colitis. 24850431 3 42 dep mice 443:446 arg1 caspase-11 426:435 caspase-11 426:435 caspase-11(-/-) 426:440 Here, we show that caspase-11 was constitutively expressed in the colon, and that caspase-11-deficient (caspase-11(-/-)) mice were hypersusceptible to dextran sodium sulfate (DSS)-induced colitis. 24850431 7 43 theme marker 1020:1025 arg1 HMGB1 1027:1031 the pyroptosis/necroptosis marker HMGB1 993:1031 the pyroptosis/necroptosis marker HMGB1 993:1031 DSS-induced tissue damage and inflammatory cell infiltration in the gut were markedly increased in caspase-11−/− mice, while release of the pyroptosis/necroptosis marker HMGB1 was abolished [Corrected]. 24850431 11 44 from role 1527:1530 arg1 protection 1595:1604 protection 1595:1604 protection against intestinal inflammation 1595:1636 These results suggest a role for other caspase-11 effector mechanisms such as pyroptosis in protection against intestinal inflammation. 24850431 8 45 theme increased 1108:1116 arg1 production 1118:1127 normal or increased production 1098:1127 normal or increased production of mature interleukin (IL)-1β and IL-18 1098:1167 Moreover, caspase-11(-/-) mice showed normal or increased production of mature interleukin (IL)-1β and IL-18, whereas IL-1β and IL-18 secretion was blunted in animals lacking both caspases 1 and 11. 24850431 11 46 theme effector 1553:1560 arg1 mechanisms 1562:1571 other caspase-11 effector mechanisms 1536:1571 other caspase-11 effector mechanisms such as pyroptosis 1536:1590 These results suggest a role for other caspase-11 effector mechanisms such as pyroptosis in protection against intestinal inflammation. 24850431 11 46 theme effector 1553:1560 arg1 pyroptosis 1581:1590 pyroptosis 1581:1590 pyroptosis 1581:1590 These results suggest a role for other caspase-11 effector mechanisms such as pyroptosis in protection against intestinal inflammation. 24850431 8 47 dep mice 1086:1089 arg1 -/- 1081:1083 -/- 1081:1083 -/- 1081:1083 Moreover, caspase-11(-/-) mice showed normal or increased production of mature interleukin (IL)-1β and IL-18, whereas IL-1β and IL-18 secretion was blunted in animals lacking both caspases 1 and 11. 24850431 7 48 theme cell 900:903 arg1 infiltration 905:916 inflammatory cell infiltration 887:916 inflammatory cell infiltration 887:916 DSS-induced tissue damage and inflammatory cell infiltration in the gut were markedly increased in caspase-11−/− mice, while release of the pyroptosis/necroptosis marker HMGB1 was abolished [Corrected]. 24850431 8 49 theme mature 1132:1137 arg1 IL 1152:1153 mature interleukin (IL)-1β 1132:1157 mature interleukin (IL)-1β 1132:1157 Moreover, caspase-11(-/-) mice showed normal or increased production of mature interleukin (IL)-1β and IL-18, whereas IL-1β and IL-18 secretion was blunted in animals lacking both caspases 1 and 11. 24850431 9 50 dep mice 1364:1367 arg1 -/- 1359:1361 -/- 1359:1361 -/- 1359:1361 In conclusion, we showed that caspase-11 shapes the gut microbiota composition, and that caspase-11(-/-) mice are highly susceptible to DSS-induced colitis. 24850431 3 51 theme -induced 501:508 arg1 colitis 510:516 dextran sodium sulfate (DSS)-induced colitis 473:516 dextran sodium sulfate (DSS)-induced colitis 473:516 Here, we show that caspase-11 was constitutively expressed in the colon, and that caspase-11-deficient (caspase-11(-/-)) mice were hypersusceptible to dextran sodium sulfate (DSS)-induced colitis. 24850431 11 52 theme caspase-11 1542:1551 arg1 mechanisms 1562:1571 other caspase-11 effector mechanisms 1536:1571 other caspase-11 effector mechanisms such as pyroptosis 1536:1590 These results suggest a role for other caspase-11 effector mechanisms such as pyroptosis in protection against intestinal inflammation. 24850431 11 52 theme caspase-11 1542:1551 arg1 pyroptosis 1581:1590 pyroptosis 1581:1590 pyroptosis 1581:1590 These results suggest a role for other caspase-11 effector mechanisms such as pyroptosis in protection against intestinal inflammation. 24850431 11 53 theme intestinal 1614:1623 arg1 inflammation 1625:1636 intestinal inflammation 1614:1636 intestinal inflammation 1614:1636 These results suggest a role for other caspase-11 effector mechanisms such as pyroptosis in protection against intestinal inflammation. 24850431 4 54 theme caspase-11 611:620 arg1 mice 627:630 caspase-11(-/-) mice 611:630 caspase-11(-/-) mice 611:630 Notably, pro-inflammatory Prevotella species were strongly reduced in the gut microbiota of caspase-11(-/-) mice. 28713776 9 0 theme infected 1321:1328 arg1 macrophages 1330:1340 Ms_rv0774c infected macrophages 1310:1340 Ms_rv0774c infected macrophages 1310:1340 However, it lowered the production of pro-inflammatory cytokines such as IL-12, TNF-α, IFN-γ, and MCP-1 in Ms_rv0774c infected macrophages in comparison to the control and could be associated with decreased phosphorylation of p38 MAPK. 28713776 9 1 theme p38 1429:1431 arg1 MAPK 1433:1436 p38 MAPK 1429:1436 p38 MAPK 1429:1436 However, it lowered the production of pro-inflammatory cytokines such as IL-12, TNF-α, IFN-γ, and MCP-1 in Ms_rv0774c infected macrophages in comparison to the control and could be associated with decreased phosphorylation of p38 MAPK. 28713776 7 2 theme expression 1065:1074 arg1 levels 1034:1039 the levels 1030:1039 the levels of reactive NO and iNOS expression 1030:1074 This could be correlated to the reduction in the levels of reactive NO and iNOS expression. 28713776 1 3 theme Mycobacterium 167:179 arg1 protein 202:208 Mycobacterium tuberculosis Rv0774c protein 167:208 Mycobacterium tuberculosis Rv0774c protein 167:208 Mycobacterium tuberculosis Rv0774c protein was reported previously to express under stress conditions. 28713776 10 4 from milieu 1552:1557 arg1 extracellular 1505:1517 extracellular 1505:1517 extracellular 1505:1517 Though, predicted with high antigenicity index bioinformatically, extracellular in nature and accessible to host milieu, Rv0774c was not able to generate humoral response in patient samples. 28713776 8 5 theme receptor 1173:1180 arg1 expression 1154:1163 significantly increased expression 1130:1163 significantly increased expression of TLR2 receptor and IL-10 cytokines 1130:1200 Infection of macrophages with Ms_rv0774c resulted in significantly increased expression of TLR2 receptor and IL-10 cytokines. 28713776 10 6 from response 1601:1608 arg1 samples 1621:1627 patient samples 1613:1627 patient samples 1613:1627 Though, predicted with high antigenicity index bioinformatically, extracellular in nature and accessible to host milieu, Rv0774c was not able to generate humoral response in patient samples. 28713776 0 7 from Line 161:164 arg1 Macrophages 144:154 Human Macrophages 138:154 Human Macrophages 138:154 Modulation of Trehalose Dimycolate and Immune System by Rv0774c Protein Enhanced the Intracellular Survival of Mycobacterium smegmatis in Human Macrophages Cell Line. 28713776 0 8 theme Intracellular 85:97 arg1 Survival 99:106 the Intracellular Survival 81:106 the Intracellular Survival of Mycobacterium smegmatis in Human Macrophages Cell Line 81:164 Modulation of Trehalose Dimycolate and Immune System by Rv0774c Protein Enhanced the Intracellular Survival of Mycobacterium smegmatis in Human Macrophages Cell Line. 28713776 5 9 contain have 750:753 arg1 envelope 707:714 The cell envelope 698:714 The cell envelope of Ms_rv0774c 698:728 The cell envelope of Ms_rv0774c was demonstrated to have more trehalose di-mycolate (TDM) and lesser amount of mycolylmannosylphosphorylheptaprenol (Myc-PL) in comparison to control. 28713776 5 9 contain have 750:753 arg2 mycolylmannosylphosphorylheptaprenol 809:844 mycolylmannosylphosphorylheptaprenol 809:844 mycolylmannosylphosphorylheptaprenol (Myc-PL) 809:853 The cell envelope of Ms_rv0774c was demonstrated to have more trehalose di-mycolate (TDM) and lesser amount of mycolylmannosylphosphorylheptaprenol (Myc-PL) in comparison to control. 28713776 5 9 contain have 750:753 arg2 TDM 783:785 TDM 783:785 TDM 783:785 The cell envelope of Ms_rv0774c was demonstrated to have more trehalose di-mycolate (TDM) and lesser amount of mycolylmannosylphosphorylheptaprenol (Myc-PL) in comparison to control. 28713776 5 9 contain have 750:753 arg2 Myc-PL 847:852 Myc-PL 847:852 Myc-PL 847:852 The cell envelope of Ms_rv0774c was demonstrated to have more trehalose di-mycolate (TDM) and lesser amount of mycolylmannosylphosphorylheptaprenol (Myc-PL) in comparison to control. 28713776 5 9 contain have 750:753 arg2 di-mycolate 770:780 more trehalose di-mycolate 755:780 more trehalose di-mycolate (TDM) 755:786 The cell envelope of Ms_rv0774c was demonstrated to have more trehalose di-mycolate (TDM) and lesser amount of mycolylmannosylphosphorylheptaprenol (Myc-PL) in comparison to control. 28713776 5 9 contain have 750:753 arg2 amount 799:804 lesser amount 792:804 lesser amount of mycolylmannosylphosphorylheptaprenol (Myc-PL) 792:853 The cell envelope of Ms_rv0774c was demonstrated to have more trehalose di-mycolate (TDM) and lesser amount of mycolylmannosylphosphorylheptaprenol (Myc-PL) in comparison to control. 28713776 9 10 theme MAPK 1433:1436 arg1 phosphorylation 1410:1424 decreased phosphorylation 1400:1424 decreased phosphorylation of p38 MAPK 1400:1436 However, it lowered the production of pro-inflammatory cytokines such as IL-12, TNF-α, IFN-γ, and MCP-1 in Ms_rv0774c infected macrophages in comparison to the control and could be associated with decreased phosphorylation of p38 MAPK. 28713776 0 11 theme Mycobacterium 111:123 arg1 smegmatis 125:133 Mycobacterium smegmatis 111:133 Mycobacterium smegmatis 111:133 Modulation of Trehalose Dimycolate and Immune System by Rv0774c Protein Enhanced the Intracellular Survival of Mycobacterium smegmatis in Human Macrophages Cell Line. 28713776 8 12 theme IL-10 1186:1190 arg1 cytokines 1192:1200 IL-10 cytokines 1186:1200 IL-10 cytokines 1186:1200 Infection of macrophages with Ms_rv0774c resulted in significantly increased expression of TLR2 receptor and IL-10 cytokines. 28713776 1 13 theme tuberculosis 181:192 arg1 protein 202:208 Mycobacterium tuberculosis Rv0774c protein 167:208 Mycobacterium tuberculosis Rv0774c protein 167:208 Mycobacterium tuberculosis Rv0774c protein was reported previously to express under stress conditions. 28713776 5 14 theme lesser 792:797 arg1 Myc-PL 847:852 Myc-PL 847:852 Myc-PL 847:852 The cell envelope of Ms_rv0774c was demonstrated to have more trehalose di-mycolate (TDM) and lesser amount of mycolylmannosylphosphorylheptaprenol (Myc-PL) in comparison to control. 28713776 5 14 theme lesser 792:797 arg1 mycolylmannosylphosphorylheptaprenol 809:844 mycolylmannosylphosphorylheptaprenol 809:844 mycolylmannosylphosphorylheptaprenol (Myc-PL) 809:853 The cell envelope of Ms_rv0774c was demonstrated to have more trehalose di-mycolate (TDM) and lesser amount of mycolylmannosylphosphorylheptaprenol (Myc-PL) in comparison to control. 28713776 5 14 theme lesser 792:797 arg1 amount 799:804 lesser amount 792:804 lesser amount of mycolylmannosylphosphorylheptaprenol (Myc-PL) 792:853 The cell envelope of Ms_rv0774c was demonstrated to have more trehalose di-mycolate (TDM) and lesser amount of mycolylmannosylphosphorylheptaprenol (Myc-PL) in comparison to control. 28713776 6 15 theme survival 902:909 arg1 rate 911:914 Higher intracellular survival rate 881:914 Higher intracellular survival rate 881:914 Higher intracellular survival rate was observed for Ms_rv0774c as compared to Ms_ve in the THP-1 cells. 28713776 10 16 theme antigenicity 1467:1478 arg1 index 1480:1484 high antigenicity index 1462:1484 high antigenicity index 1462:1484 Though, predicted with high antigenicity index bioinformatically, extracellular in nature and accessible to host milieu, Rv0774c was not able to generate humoral response in patient samples. 28713776 11 17 theme lipid 1751:1755 arg1 composition 1757:1767 the lipid composition 1747:1767 the lipid composition of M. smegmatis 1747:1783 Overall, the present findings indicated that Rv0774c altered the morphology and streptomycin sensitivity by altering the lipid composition of M. smegmatis as well as modulated the immune response in favor of bacterial persistence. 28713776 4 18 theme Enhanced 591:598 arg1 survival 600:607 Enhanced survival 591:607 Enhanced survival of Ms_rv0774c after treatment with streptomycin 591:655 Enhanced survival of Ms_rv0774c after treatment with streptomycin was observed when compared with control. 28713776 1 19 theme Rv0774c 194:200 arg1 protein 202:208 Mycobacterium tuberculosis Rv0774c protein 167:208 Mycobacterium tuberculosis Rv0774c protein 167:208 Mycobacterium tuberculosis Rv0774c protein was reported previously to express under stress conditions. 28713776 6 20 theme intracellular 888:900 arg1 rate 911:914 Higher intracellular survival rate 881:914 Higher intracellular survival rate 881:914 Higher intracellular survival rate was observed for Ms_rv0774c as compared to Ms_ve in the THP-1 cells. 28713776 10 21 theme high 1462:1465 arg1 index 1480:1484 high antigenicity index 1462:1484 high antigenicity index 1462:1484 Though, predicted with high antigenicity index bioinformatically, extracellular in nature and accessible to host milieu, Rv0774c was not able to generate humoral response in patient samples. 28713776 8 22 theme increased 1144:1152 arg1 expression 1154:1163 significantly increased expression 1130:1163 significantly increased expression of TLR2 receptor and IL-10 cytokines 1130:1200 Infection of macrophages with Ms_rv0774c resulted in significantly increased expression of TLR2 receptor and IL-10 cytokines. 28713776 3 23 theme control 569:575 arg1 Ms_ve 583:587 Ms_ve 583:587 Ms_ve 583:587 The bacterial colonies expressing Rv0774c (Ms_rv0774c) were larger, smoother, more moist, and flatter than the control ones (Ms_ve). 28713776 3 23 theme control 569:575 arg1 ones 577:580 the control ones 565:580 the control ones (Ms_ve) 565:588 The bacterial colonies expressing Rv0774c (Ms_rv0774c) were larger, smoother, more moist, and flatter than the control ones (Ms_ve). 28713776 7 24 theme reactive 1044:1051 arg1 NO 1053:1054 reactive NO 1044:1054 reactive NO 1044:1054 This could be correlated to the reduction in the levels of reactive NO and iNOS expression. 28713776 2 25 theme bacterial 390:398 arg1 persistence 400:410 bacterial persistence 390:410 bacterial persistence 390:410 Therefore, Rv0774c gene was cloned and expressed in Mycobacterium smegmatis, a surrogate host, to determine its role in bacterial persistence and immune modulation in natural environment. 28713776 8 26 theme cytokines 1192:1200 arg1 expression 1154:1163 significantly increased expression 1130:1163 significantly increased expression of TLR2 receptor and IL-10 cytokines 1130:1200 Infection of macrophages with Ms_rv0774c resulted in significantly increased expression of TLR2 receptor and IL-10 cytokines. 28713776 10 27 theme patient 1613:1619 arg1 samples 1621:1627 patient samples 1613:1627 patient samples 1613:1627 Though, predicted with high antigenicity index bioinformatically, extracellular in nature and accessible to host milieu, Rv0774c was not able to generate humoral response in patient samples. 28713776 2 28 from role 382:385 arg1 persistence 400:410 bacterial persistence 390:410 bacterial persistence 390:410 Therefore, Rv0774c gene was cloned and expressed in Mycobacterium smegmatis, a surrogate host, to determine its role in bacterial persistence and immune modulation in natural environment. 28713776 2 28 from role 382:385 arg1 modulation 423:432 immune modulation 416:432 immune modulation 416:432 Therefore, Rv0774c gene was cloned and expressed in Mycobacterium smegmatis, a surrogate host, to determine its role in bacterial persistence and immune modulation in natural environment. 28713776 2 28 from role 382:385 arg1 environment 445:455 natural environment 437:455 natural environment 437:455 Therefore, Rv0774c gene was cloned and expressed in Mycobacterium smegmatis, a surrogate host, to determine its role in bacterial persistence and immune modulation in natural environment. 28713776 11 29 theme streptomycin 1710:1721 arg1 sensitivity 1723:1733 streptomycin sensitivity 1710:1733 streptomycin sensitivity 1710:1733 Overall, the present findings indicated that Rv0774c altered the morphology and streptomycin sensitivity by altering the lipid composition of M. smegmatis as well as modulated the immune response in favor of bacterial persistence. 28713776 0 30 theme Dimycolate 24:33 arg1 Modulation 0:9 Modulation 0:9 Modulation of Trehalose Dimycolate and Immune System by Rv0774c Protein 0:70 Modulation of Trehalose Dimycolate and Immune System by Rv0774c Protein Enhanced the Intracellular Survival of Mycobacterium smegmatis in Human Macrophages Cell Line. 28713776 5 31 theme cell 702:705 arg1 envelope 707:714 The cell envelope 698:714 The cell envelope of Ms_rv0774c 698:728 The cell envelope of Ms_rv0774c was demonstrated to have more trehalose di-mycolate (TDM) and lesser amount of mycolylmannosylphosphorylheptaprenol (Myc-PL) in comparison to control. 28713776 10 32 theme humoral 1593:1599 arg1 response 1601:1608 humoral response 1593:1608 humoral response in patient samples 1593:1627 Though, predicted with high antigenicity index bioinformatically, extracellular in nature and accessible to host milieu, Rv0774c was not able to generate humoral response in patient samples. 28713776 2 33 theme natural 437:443 arg1 environment 445:455 natural environment 437:455 natural environment 437:455 Therefore, Rv0774c gene was cloned and expressed in Mycobacterium smegmatis, a surrogate host, to determine its role in bacterial persistence and immune modulation in natural environment. 28713776 0 34 theme Trehalose 14:22 arg1 Dimycolate 24:33 Trehalose Dimycolate 14:33 Trehalose Dimycolate 14:33 Modulation of Trehalose Dimycolate and Immune System by Rv0774c Protein Enhanced the Intracellular Survival of Mycobacterium smegmatis in Human Macrophages Cell Line. 28713776 6 35 theme THP-1 972:976 arg1 cells 978:982 the THP-1 cells 968:982 the THP-1 cells 968:982 Higher intracellular survival rate was observed for Ms_rv0774c as compared to Ms_ve in the THP-1 cells. 28713776 0 36 theme smegmatis 125:133 arg1 Survival 99:106 the Intracellular Survival 81:106 the Intracellular Survival of Mycobacterium smegmatis in Human Macrophages Cell Line 81:164 Modulation of Trehalose Dimycolate and Immune System by Rv0774c Protein Enhanced the Intracellular Survival of Mycobacterium smegmatis in Human Macrophages Cell Line. 28713776 6 37 theme Higher 881:886 arg1 rate 911:914 Higher intracellular survival rate 881:914 Higher intracellular survival rate 881:914 Higher intracellular survival rate was observed for Ms_rv0774c as compared to Ms_ve in the THP-1 cells. 28713776 11 38 theme smegmatis 1775:1783 arg1 composition 1757:1767 the lipid composition 1747:1767 the lipid composition of M. smegmatis 1747:1783 Overall, the present findings indicated that Rv0774c altered the morphology and streptomycin sensitivity by altering the lipid composition of M. smegmatis as well as modulated the immune response in favor of bacterial persistence. 28713776 10 39 from extracellular 1505:1517 arg1 milieu 1552:1557 accessible to host milieu 1533:1557 accessible to host milieu 1533:1557 Though, predicted with high antigenicity index bioinformatically, extracellular in nature and accessible to host milieu, Rv0774c was not able to generate humoral response in patient samples. 28713776 10 39 from extracellular 1505:1517 arg1 nature 1522:1527 nature 1522:1527 nature 1522:1527 Though, predicted with high antigenicity index bioinformatically, extracellular in nature and accessible to host milieu, Rv0774c was not able to generate humoral response in patient samples. 28713776 0 40 theme Immune 39:44 arg1 System 46:51 Immune System 39:51 Immune System 39:51 Modulation of Trehalose Dimycolate and Immune System by Rv0774c Protein Enhanced the Intracellular Survival of Mycobacterium smegmatis in Human Macrophages Cell Line. 28713776 7 41 theme NO 1053:1054 arg1 levels 1034:1039 the levels 1030:1039 the levels of reactive NO and iNOS expression 1030:1074 This could be correlated to the reduction in the levels of reactive NO and iNOS expression. 28713776 9 42 theme pro-inflammatory 1241:1256 arg1 cytokines 1258:1266 pro-inflammatory cytokines 1241:1266 pro-inflammatory cytokines such as IL-12, TNF-α, IFN-γ, and MCP-1 1241:1305 However, it lowered the production of pro-inflammatory cytokines such as IL-12, TNF-α, IFN-γ, and MCP-1 in Ms_rv0774c infected macrophages in comparison to the control and could be associated with decreased phosphorylation of p38 MAPK. 28713776 9 42 theme pro-inflammatory 1241:1256 arg1 IL-12 1276:1280 IL-12 1276:1280 IL-12 1276:1280 However, it lowered the production of pro-inflammatory cytokines such as IL-12, TNF-α, IFN-γ, and MCP-1 in Ms_rv0774c infected macrophages in comparison to the control and could be associated with decreased phosphorylation of p38 MAPK. 28713776 9 42 theme pro-inflammatory 1241:1256 arg1 IFN-γ 1290:1294 IFN-γ 1290:1294 IFN-γ 1290:1294 However, it lowered the production of pro-inflammatory cytokines such as IL-12, TNF-α, IFN-γ, and MCP-1 in Ms_rv0774c infected macrophages in comparison to the control and could be associated with decreased phosphorylation of p38 MAPK. 28713776 9 42 theme pro-inflammatory 1241:1256 arg1 MCP-1 1301:1305 MCP-1 1301:1305 MCP-1 1301:1305 However, it lowered the production of pro-inflammatory cytokines such as IL-12, TNF-α, IFN-γ, and MCP-1 in Ms_rv0774c infected macrophages in comparison to the control and could be associated with decreased phosphorylation of p38 MAPK. 28713776 9 42 theme pro-inflammatory 1241:1256 arg1 TNF-α 1283:1287 TNF-α 1283:1287 TNF-α 1283:1287 However, it lowered the production of pro-inflammatory cytokines such as IL-12, TNF-α, IFN-γ, and MCP-1 in Ms_rv0774c infected macrophages in comparison to the control and could be associated with decreased phosphorylation of p38 MAPK. 28713776 5 43 theme Ms_rv0774c 719:728 arg1 envelope 707:714 The cell envelope 698:714 The cell envelope of Ms_rv0774c 698:728 The cell envelope of Ms_rv0774c was demonstrated to have more trehalose di-mycolate (TDM) and lesser amount of mycolylmannosylphosphorylheptaprenol (Myc-PL) in comparison to control. 28713776 7 44 from reduction 1017:1025 arg1 levels 1034:1039 the levels 1030:1039 the levels of reactive NO and iNOS expression 1030:1074 This could be correlated to the reduction in the levels of reactive NO and iNOS expression. 28713776 0 45 theme Human 138:142 arg1 Macrophages 144:154 Human Macrophages 138:154 Human Macrophages 138:154 Modulation of Trehalose Dimycolate and Immune System by Rv0774c Protein Enhanced the Intracellular Survival of Mycobacterium smegmatis in Human Macrophages Cell Line. 28713776 9 46 theme cytokines 1258:1266 arg1 production 1227:1236 the production 1223:1236 the production of pro-inflammatory cytokines such as IL-12, TNF-α, IFN-γ, and MCP-1 in Ms_rv0774c infected macrophages 1223:1340 However, it lowered the production of pro-inflammatory cytokines such as IL-12, TNF-α, IFN-γ, and MCP-1 in Ms_rv0774c infected macrophages in comparison to the control and could be associated with decreased phosphorylation of p38 MAPK. 28713776 5 47 theme mycolylmannosylphosphorylheptaprenol 809:844 arg1 mycolylmannosylphosphorylheptaprenol 809:844 mycolylmannosylphosphorylheptaprenol 809:844 mycolylmannosylphosphorylheptaprenol (Myc-PL) 809:853 The cell envelope of Ms_rv0774c was demonstrated to have more trehalose di-mycolate (TDM) and lesser amount of mycolylmannosylphosphorylheptaprenol (Myc-PL) in comparison to control. 28713776 5 47 theme mycolylmannosylphosphorylheptaprenol 809:844 arg1 Myc-PL 847:852 Myc-PL 847:852 Myc-PL 847:852 The cell envelope of Ms_rv0774c was demonstrated to have more trehalose di-mycolate (TDM) and lesser amount of mycolylmannosylphosphorylheptaprenol (Myc-PL) in comparison to control. 28713776 5 47 theme mycolylmannosylphosphorylheptaprenol 809:844 arg1 di-mycolate 770:780 more trehalose di-mycolate 755:780 more trehalose di-mycolate (TDM) 755:786 The cell envelope of Ms_rv0774c was demonstrated to have more trehalose di-mycolate (TDM) and lesser amount of mycolylmannosylphosphorylheptaprenol (Myc-PL) in comparison to control. 28713776 5 47 theme mycolylmannosylphosphorylheptaprenol 809:844 arg1 TDM 783:785 TDM 783:785 TDM 783:785 The cell envelope of Ms_rv0774c was demonstrated to have more trehalose di-mycolate (TDM) and lesser amount of mycolylmannosylphosphorylheptaprenol (Myc-PL) in comparison to control. 28713776 5 47 theme mycolylmannosylphosphorylheptaprenol 809:844 arg1 amount 799:804 lesser amount 792:804 lesser amount of mycolylmannosylphosphorylheptaprenol (Myc-PL) 792:853 The cell envelope of Ms_rv0774c was demonstrated to have more trehalose di-mycolate (TDM) and lesser amount of mycolylmannosylphosphorylheptaprenol (Myc-PL) in comparison to control. 28713776 11 48 theme M. 1772:1773 arg1 smegmatis 1775:1783 M. smegmatis 1772:1783 M. smegmatis 1772:1783 Overall, the present findings indicated that Rv0774c altered the morphology and streptomycin sensitivity by altering the lipid composition of M. smegmatis as well as modulated the immune response in favor of bacterial persistence. 28713776 2 49 theme immune 416:421 arg1 modulation 423:432 immune modulation 416:432 immune modulation 416:432 Therefore, Rv0774c gene was cloned and expressed in Mycobacterium smegmatis, a surrogate host, to determine its role in bacterial persistence and immune modulation in natural environment. 28713776 7 50 theme iNOS 1060:1063 arg1 expression 1065:1074 iNOS expression 1060:1074 iNOS expression 1060:1074 This could be correlated to the reduction in the levels of reactive NO and iNOS expression. 28713776 11 51 theme bacterial 1838:1846 arg1 persistence 1848:1858 bacterial persistence 1838:1858 bacterial persistence 1838:1858 Overall, the present findings indicated that Rv0774c altered the morphology and streptomycin sensitivity by altering the lipid composition of M. smegmatis as well as modulated the immune response in favor of bacterial persistence. 28713776 5 52 theme trehalose 760:768 arg1 TDM 783:785 TDM 783:785 TDM 783:785 The cell envelope of Ms_rv0774c was demonstrated to have more trehalose di-mycolate (TDM) and lesser amount of mycolylmannosylphosphorylheptaprenol (Myc-PL) in comparison to control. 28713776 5 52 theme trehalose 760:768 arg1 di-mycolate 770:780 more trehalose di-mycolate 755:780 more trehalose di-mycolate (TDM) 755:786 The cell envelope of Ms_rv0774c was demonstrated to have more trehalose di-mycolate (TDM) and lesser amount of mycolylmannosylphosphorylheptaprenol (Myc-PL) in comparison to control. 28713776 9 53 theme Ms_rv0774c 1310:1319 arg1 macrophages 1330:1340 Ms_rv0774c infected macrophages 1310:1340 Ms_rv0774c infected macrophages 1310:1340 However, it lowered the production of pro-inflammatory cytokines such as IL-12, TNF-α, IFN-γ, and MCP-1 in Ms_rv0774c infected macrophages in comparison to the control and could be associated with decreased phosphorylation of p38 MAPK. 28713776 10 54 theme accessible 1533:1542 arg1 milieu 1552:1557 accessible to host milieu 1533:1557 accessible to host milieu 1533:1557 Though, predicted with high antigenicity index bioinformatically, extracellular in nature and accessible to host milieu, Rv0774c was not able to generate humoral response in patient samples. 28713776 0 55 theme System 46:51 arg1 Modulation 0:9 Modulation 0:9 Modulation of Trehalose Dimycolate and Immune System by Rv0774c Protein 0:70 Modulation of Trehalose Dimycolate and Immune System by Rv0774c Protein Enhanced the Intracellular Survival of Mycobacterium smegmatis in Human Macrophages Cell Line. 28713776 0 56 theme Cell 156:159 arg1 Line 161:164 Cell Line 156:164 Cell Line 156:164 Modulation of Trehalose Dimycolate and Immune System by Rv0774c Protein Enhanced the Intracellular Survival of Mycobacterium smegmatis in Human Macrophages Cell Line. 28713776 10 57 from nature 1522:1527 arg1 extracellular 1505:1517 extracellular 1505:1517 extracellular 1505:1517 Though, predicted with high antigenicity index bioinformatically, extracellular in nature and accessible to host milieu, Rv0774c was not able to generate humoral response in patient samples. 28713776 9 58 from production 1227:1236 arg1 macrophages 1330:1340 Ms_rv0774c infected macrophages 1310:1340 Ms_rv0774c infected macrophages 1310:1340 However, it lowered the production of pro-inflammatory cytokines such as IL-12, TNF-α, IFN-γ, and MCP-1 in Ms_rv0774c infected macrophages in comparison to the control and could be associated with decreased phosphorylation of p38 MAPK. 28713776 8 59 theme macrophages 1090:1100 arg1 Infection 1077:1085 Infection 1077:1085 Infection of macrophages with Ms_rv0774c 1077:1116 Infection of macrophages with Ms_rv0774c resulted in significantly increased expression of TLR2 receptor and IL-10 cytokines. 28713776 9 60 dep control 1363:1369 arg1 comparison 1345:1354 comparison 1345:1354 comparison 1345:1354 However, it lowered the production of pro-inflammatory cytokines such as IL-12, TNF-α, IFN-γ, and MCP-1 in Ms_rv0774c infected macrophages in comparison to the control and could be associated with decreased phosphorylation of p38 MAPK. 28713776 11 61 theme immune 1810:1815 arg1 response 1817:1824 the immune response 1806:1824 the immune response 1806:1824 Overall, the present findings indicated that Rv0774c altered the morphology and streptomycin sensitivity by altering the lipid composition of M. smegmatis as well as modulated the immune response in favor of bacterial persistence. 28713776 2 62 theme surrogate 349:357 arg1 host 359:362 a surrogate host 347:362 a surrogate host 347:362 Therefore, Rv0774c gene was cloned and expressed in Mycobacterium smegmatis, a surrogate host, to determine its role in bacterial persistence and immune modulation in natural environment. 28713776 2 62 theme surrogate 349:357 arg1 smegmatis 336:344 Mycobacterium smegmatis 322:344 Mycobacterium smegmatis 322:344 Therefore, Rv0774c gene was cloned and expressed in Mycobacterium smegmatis, a surrogate host, to determine its role in bacterial persistence and immune modulation in natural environment. 28713776 6 63 from Ms_ve 959:963 arg1 cells 978:982 the THP-1 cells 968:982 the THP-1 cells 968:982 Higher intracellular survival rate was observed for Ms_rv0774c as compared to Ms_ve in the THP-1 cells. 28713776 4 64 with treatment 629:637 arg1 streptomycin 644:655 streptomycin 644:655 streptomycin 644:655 Enhanced survival of Ms_rv0774c after treatment with streptomycin was observed when compared with control. 28713776 2 65 theme Rv0774c 281:287 arg1 gene 289:292 Rv0774c gene 281:292 Rv0774c gene 281:292 Therefore, Rv0774c gene was cloned and expressed in Mycobacterium smegmatis, a surrogate host, to determine its role in bacterial persistence and immune modulation in natural environment. 28713776 8 66 with Infection 1077:1085 arg1 Ms_rv0774c 1107:1116 Ms_rv0774c 1107:1116 Ms_rv0774c 1107:1116 Infection of macrophages with Ms_rv0774c resulted in significantly increased expression of TLR2 receptor and IL-10 cytokines. 28713776 1 67 theme stress 251:256 arg1 conditions 258:267 stress conditions 251:267 stress conditions 251:267 Mycobacterium tuberculosis Rv0774c protein was reported previously to express under stress conditions. 28713776 5 68 theme more 755:758 arg1 TDM 783:785 TDM 783:785 TDM 783:785 The cell envelope of Ms_rv0774c was demonstrated to have more trehalose di-mycolate (TDM) and lesser amount of mycolylmannosylphosphorylheptaprenol (Myc-PL) in comparison to control. 28713776 5 68 theme more 755:758 arg1 di-mycolate 770:780 more trehalose di-mycolate 755:780 more trehalose di-mycolate (TDM) 755:786 The cell envelope of Ms_rv0774c was demonstrated to have more trehalose di-mycolate (TDM) and lesser amount of mycolylmannosylphosphorylheptaprenol (Myc-PL) in comparison to control. 28713776 10 69 theme host 1547:1550 arg1 milieu 1552:1557 accessible to host milieu 1533:1557 accessible to host milieu 1533:1557 Though, predicted with high antigenicity index bioinformatically, extracellular in nature and accessible to host milieu, Rv0774c was not able to generate humoral response in patient samples. 28713776 3 70 theme bacterial 462:470 arg1 larger 518:523 larger 518:523 larger 518:523 The bacterial colonies expressing Rv0774c (Ms_rv0774c) were larger, smoother, more moist, and flatter than the control ones (Ms_ve). 28713776 3 70 theme bacterial 462:470 arg1 colonies 472:479 The bacterial colonies 458:479 The bacterial colonies expressing Rv0774c (Ms_rv0774c) 458:511 The bacterial colonies expressing Rv0774c (Ms_rv0774c) were larger, smoother, more moist, and flatter than the control ones (Ms_ve). 28713776 4 71 theme Ms_rv0774c 612:621 arg1 survival 600:607 Enhanced survival 591:607 Enhanced survival of Ms_rv0774c after treatment with streptomycin 591:655 Enhanced survival of Ms_rv0774c after treatment with streptomycin was observed when compared with control. 28713776 0 72 theme Rv0774c 56:62 arg1 Protein 64:70 Rv0774c Protein 56:70 Rv0774c Protein 56:70 Modulation of Trehalose Dimycolate and Immune System by Rv0774c Protein Enhanced the Intracellular Survival of Mycobacterium smegmatis in Human Macrophages Cell Line. 28713776 11 73 theme present 1643:1649 arg1 findings 1651:1658 the present findings 1639:1658 the present findings 1639:1658 Overall, the present findings indicated that Rv0774c altered the morphology and streptomycin sensitivity by altering the lipid composition of M. smegmatis as well as modulated the immune response in favor of bacterial persistence. 28713776 9 74 theme decreased 1400:1408 arg1 phosphorylation 1410:1424 decreased phosphorylation 1400:1424 decreased phosphorylation of p38 MAPK 1400:1436 However, it lowered the production of pro-inflammatory cytokines such as IL-12, TNF-α, IFN-γ, and MCP-1 in Ms_rv0774c infected macrophages in comparison to the control and could be associated with decreased phosphorylation of p38 MAPK. 28713776 8 75 theme TLR2 1168:1171 arg1 receptor 1173:1180 TLR2 receptor 1168:1180 TLR2 receptor 1168:1180 Infection of macrophages with Ms_rv0774c resulted in significantly increased expression of TLR2 receptor and IL-10 cytokines. 28462053 7 0 theme prediction 1211:1220 arg1 methods 1222:1228 the existing prediction methods 1198:1228 the existing prediction methods 1198:1228 The experimental results revealed that the proposed method performed comparable or better performance than the existing prediction methods, suggesting the feasibility of the developed kernels and the usefulness of the proposed method in PTM sites prediction. 28462053 2 1 theme sites 392:396 arg1 prediction 374:383 the prediction 370:383 the prediction of PTM sites 370:396 Considering the high-cost and labor-intensive of experimental identification, many computational prediction methods are currently available for the prediction of PTM sites by using protein local sequence information in the context of conserved motif. 28462053 4 2 theme local 813:817 arg1 kernel 828:833 a local sequence kernel 811:833 a local sequence kernel 811:833 To largely make use of local sequence information and site-modification relationships, we developed a local sequence kernel and Gaussian interaction profile kernel, respectively. 28462053 6 3 theme prediction 1071:1080 arg1 methods 1082:1088 PTM prediction methods 1067:1088 PTM prediction methods 1067:1088 We compared the proposed method with existing PTM prediction methods. 28462053 7 4 theme comparable 1160:1169 arg1 performance 1181:1191 comparable or better performance 1160:1191 comparable or better performance 1160:1191 The experimental results revealed that the proposed method performed comparable or better performance than the existing prediction methods, suggesting the feasibility of the developed kernels and the usefulness of the proposed method in PTM sites prediction. 28462053 7 5 theme existing 1202:1209 arg1 methods 1222:1228 the existing prediction methods 1198:1228 the existing prediction methods 1198:1228 The experimental results revealed that the proposed method performed comparable or better performance than the existing prediction methods, suggesting the feasibility of the developed kernels and the usefulness of the proposed method in PTM sites prediction. 28462053 2 6 theme PTM 388:390 arg1 sites 392:396 PTM sites 388:396 PTM sites 388:396 Considering the high-cost and labor-intensive of experimental identification, many computational prediction methods are currently available for the prediction of PTM sites by using protein local sequence information in the context of conserved motif. 28462053 5 7 theme predictive 997:1006 arg1 performance 1008:1018 predictive performance 997:1018 predictive performance 997:1018 Multiple kernels were further combined to train SVM for efficiently leveraging kernel information to boost predictive performance. 28462053 7 8 from feasibility 1246:1256 arg1 prediction 1338:1347 PTM sites prediction 1328:1347 PTM sites prediction 1328:1347 The experimental results revealed that the proposed method performed comparable or better performance than the existing prediction methods, suggesting the feasibility of the developed kernels and the usefulness of the proposed method in PTM sites prediction. 28462053 2 9 theme prediction 323:332 arg1 methods 334:340 many computational prediction methods 304:340 many computational prediction methods 304:340 Considering the high-cost and labor-intensive of experimental identification, many computational prediction methods are currently available for the prediction of PTM sites by using protein local sequence information in the context of conserved motif. 28462053 4 10 theme relationships 783:795 arg1 use 727:729 use 727:729 use of local sequence information and site-modification relationships 727:795 To largely make use of local sequence information and site-modification relationships, we developed a local sequence kernel and Gaussian interaction profile kernel, respectively. 28462053 3 11 theme machines 582:589 arg1 combination 536:546 the combination 532:546 the combination of multiple kernel support vector machines (SVM) for predicting PTM sites including phosphorylation, O-linked glycosylation, acetylation, sulfation and nitration 532:708 Here we proposed a novel computational method by using the combination of multiple kernel support vector machines (SVM) for predicting PTM sites including phosphorylation, O-linked glycosylation, acetylation, sulfation and nitration. 28462053 2 12 theme computational 309:321 arg1 methods 334:340 many computational prediction methods 304:340 many computational prediction methods 304:340 Considering the high-cost and labor-intensive of experimental identification, many computational prediction methods are currently available for the prediction of PTM sites by using protein local sequence information in the context of conserved motif. 28462053 5 13 theme kernel 969:974 arg1 information 976:986 kernel information 969:986 kernel information 969:986 Multiple kernels were further combined to train SVM for efficiently leveraging kernel information to boost predictive performance. 28462053 5 14 theme Multiple 890:897 arg1 kernels 899:905 Multiple kernels 890:905 Multiple kernels 890:905 Multiple kernels were further combined to train SVM for efficiently leveraging kernel information to boost predictive performance. 28462053 3 15 theme novel 496:500 arg1 method 516:521 a novel computational method 494:521 a novel computational method 494:521 Here we proposed a novel computational method by using the combination of multiple kernel support vector machines (SVM) for predicting PTM sites including phosphorylation, O-linked glycosylation, acetylation, sulfation and nitration. 28462053 2 16 theme many 304:307 arg1 methods 334:340 many computational prediction methods 304:340 many computational prediction methods 304:340 Considering the high-cost and labor-intensive of experimental identification, many computational prediction methods are currently available for the prediction of PTM sites by using protein local sequence information in the context of conserved motif. 28462053 3 17 theme support 567:573 arg1 SVM 592:594 SVM 592:594 SVM 592:594 Here we proposed a novel computational method by using the combination of multiple kernel support vector machines (SVM) for predicting PTM sites including phosphorylation, O-linked glycosylation, acetylation, sulfation and nitration. 28462053 3 17 theme support 567:573 arg1 machines 582:589 multiple kernel support vector machines 551:589 multiple kernel support vector machines (SVM) 551:595 Here we proposed a novel computational method by using the combination of multiple kernel support vector machines (SVM) for predicting PTM sites including phosphorylation, O-linked glycosylation, acetylation, sulfation and nitration. 28462053 2 18 theme sequence 421:428 arg1 information 430:440 protein local sequence information 407:440 protein local sequence information 407:440 Considering the high-cost and labor-intensive of experimental identification, many computational prediction methods are currently available for the prediction of PTM sites by using protein local sequence information in the context of conserved motif. 28462053 7 19 theme developed 1265:1273 arg1 kernels 1275:1281 the developed kernels 1261:1281 the developed kernels 1261:1281 The experimental results revealed that the proposed method performed comparable or better performance than the existing prediction methods, suggesting the feasibility of the developed kernels and the usefulness of the proposed method in PTM sites prediction. 28462053 7 20 theme proposed 1309:1316 arg1 method 1318:1323 the proposed method 1305:1323 the proposed method 1305:1323 The experimental results revealed that the proposed method performed comparable or better performance than the existing prediction methods, suggesting the feasibility of the developed kernels and the usefulness of the proposed method in PTM sites prediction. 28462053 7 21 theme method 1318:1323 arg1 usefulness 1291:1300 the usefulness 1287:1300 the usefulness of the proposed method in PTM sites prediction 1287:1347 The experimental results revealed that the proposed method performed comparable or better performance than the existing prediction methods, suggesting the feasibility of the developed kernels and the usefulness of the proposed method in PTM sites prediction. 28462053 7 21 theme method 1318:1323 arg1 feasibility 1246:1256 the feasibility 1242:1256 the feasibility of the developed kernels 1242:1281 The experimental results revealed that the proposed method performed comparable or better performance than the existing prediction methods, suggesting the feasibility of the developed kernels and the usefulness of the proposed method in PTM sites prediction. 28462053 1 22 theme Protein 98:104 arg1 mechanism 160:168 an important mechanism 147:168 an important mechanism that is involved in the regulation of protein function 147:223 Protein post-translational modification (PTM) is an important mechanism that is involved in the regulation of protein function. 28462053 1 22 theme Protein 98:104 arg1 PTM 139:141 PTM 139:141 PTM 139:141 Protein post-translational modification (PTM) is an important mechanism that is involved in the regulation of protein function. 28462053 1 22 theme Protein 98:104 arg1 modification 125:136 Protein post-translational modification 98:136 Protein post-translational modification (PTM) 98:142 Protein post-translational modification (PTM) is an important mechanism that is involved in the regulation of protein function. 28462053 2 23 theme local 415:419 arg1 information 430:440 protein local sequence information 407:440 protein local sequence information 407:440 Considering the high-cost and labor-intensive of experimental identification, many computational prediction methods are currently available for the prediction of PTM sites by using protein local sequence information in the context of conserved motif. 28462053 7 24 theme kernels 1275:1281 arg1 usefulness 1291:1300 the usefulness 1287:1300 the usefulness of the proposed method in PTM sites prediction 1287:1347 The experimental results revealed that the proposed method performed comparable or better performance than the existing prediction methods, suggesting the feasibility of the developed kernels and the usefulness of the proposed method in PTM sites prediction. 28462053 7 24 theme kernels 1275:1281 arg1 feasibility 1246:1256 the feasibility 1242:1256 the feasibility of the developed kernels 1242:1281 The experimental results revealed that the proposed method performed comparable or better performance than the existing prediction methods, suggesting the feasibility of the developed kernels and the usefulness of the proposed method in PTM sites prediction. 28462053 7 25 theme better 1174:1179 arg1 performance 1181:1191 comparable or better performance 1160:1191 comparable or better performance 1160:1191 The experimental results revealed that the proposed method performed comparable or better performance than the existing prediction methods, suggesting the feasibility of the developed kernels and the usefulness of the proposed method in PTM sites prediction. 28462053 1 26 theme post-translational 106:123 arg1 mechanism 160:168 an important mechanism 147:168 an important mechanism that is involved in the regulation of protein function 147:223 Protein post-translational modification (PTM) is an important mechanism that is involved in the regulation of protein function. 28462053 1 26 theme post-translational 106:123 arg1 PTM 139:141 PTM 139:141 PTM 139:141 Protein post-translational modification (PTM) is an important mechanism that is involved in the regulation of protein function. 28462053 1 26 theme post-translational 106:123 arg1 modification 125:136 Protein post-translational modification 98:136 Protein post-translational modification (PTM) 98:142 Protein post-translational modification (PTM) is an important mechanism that is involved in the regulation of protein function. 28462053 2 27 theme protein 407:413 arg1 information 430:440 protein local sequence information 407:440 protein local sequence information 407:440 Considering the high-cost and labor-intensive of experimental identification, many computational prediction methods are currently available for the prediction of PTM sites by using protein local sequence information in the context of conserved motif. 28462053 2 28 theme motif 470:474 arg1 context 449:455 the context 445:455 the context of conserved motif 445:474 Considering the high-cost and labor-intensive of experimental identification, many computational prediction methods are currently available for the prediction of PTM sites by using protein local sequence information in the context of conserved motif. 28462053 4 29 theme site-modification 765:781 arg1 relationships 783:795 site-modification relationships 765:795 site-modification relationships 765:795 To largely make use of local sequence information and site-modification relationships, we developed a local sequence kernel and Gaussian interaction profile kernel, respectively. 28462053 3 30 link O-linked 649:656 arg1 glycosylation 658:670 O-linked glycosylation 649:670 O-linked glycosylation 649:670 Here we proposed a novel computational method by using the combination of multiple kernel support vector machines (SVM) for predicting PTM sites including phosphorylation, O-linked glycosylation, acetylation, sulfation and nitration. 28462053 2 31 theme conserved 460:468 arg1 motif 470:474 conserved motif 460:474 conserved motif 460:474 Considering the high-cost and labor-intensive of experimental identification, many computational prediction methods are currently available for the prediction of PTM sites by using protein local sequence information in the context of conserved motif. 28462053 3 32 theme kernel 560:565 arg1 SVM 592:594 SVM 592:594 SVM 592:594 Here we proposed a novel computational method by using the combination of multiple kernel support vector machines (SVM) for predicting PTM sites including phosphorylation, O-linked glycosylation, acetylation, sulfation and nitration. 28462053 3 32 theme kernel 560:565 arg1 machines 582:589 multiple kernel support vector machines 551:589 multiple kernel support vector machines (SVM) 551:595 Here we proposed a novel computational method by using the combination of multiple kernel support vector machines (SVM) for predicting PTM sites including phosphorylation, O-linked glycosylation, acetylation, sulfation and nitration. 28462053 7 33 theme sites 1332:1336 arg1 prediction 1338:1347 PTM sites prediction 1328:1347 PTM sites prediction 1328:1347 The experimental results revealed that the proposed method performed comparable or better performance than the existing prediction methods, suggesting the feasibility of the developed kernels and the usefulness of the proposed method in PTM sites prediction. 28462053 1 34 theme protein 208:214 arg1 function 216:223 protein function 208:223 protein function 208:223 Protein post-translational modification (PTM) is an important mechanism that is involved in the regulation of protein function. 28462053 7 35 theme proposed 1134:1141 arg1 method 1143:1148 the proposed method 1130:1148 the proposed method 1130:1148 The experimental results revealed that the proposed method performed comparable or better performance than the existing prediction methods, suggesting the feasibility of the developed kernels and the usefulness of the proposed method in PTM sites prediction. 28462053 1 36 theme function 216:223 arg1 regulation 194:203 the regulation 190:203 the regulation of protein function 190:223 Protein post-translational modification (PTM) is an important mechanism that is involved in the regulation of protein function. 28462053 0 37 theme sites 46:50 arg1 Prediction 0:9 Prediction 0:9 Prediction of post-translational modification sites 0:50 Prediction of post-translational modification sites using multiple kernel support vector machine. 28462053 6 38 theme PTM 1067:1069 arg1 methods 1082:1088 PTM prediction methods 1067:1088 PTM prediction methods 1067:1088 We compared the proposed method with existing PTM prediction methods. 28462053 7 39 from usefulness 1291:1300 arg1 prediction 1338:1347 PTM sites prediction 1328:1347 PTM sites prediction 1328:1347 The experimental results revealed that the proposed method performed comparable or better performance than the existing prediction methods, suggesting the feasibility of the developed kernels and the usefulness of the proposed method in PTM sites prediction. 28462053 0 40 theme modification 33:44 arg1 sites 46:50 post-translational modification sites 14:50 post-translational modification sites 14:50 Prediction of post-translational modification sites using multiple kernel support vector machine. 28462053 0 41 theme kernel 67:72 arg1 machine 89:95 multiple kernel support vector machine 58:95 multiple kernel support vector machine 58:95 Prediction of post-translational modification sites using multiple kernel support vector machine. 28462053 6 42 theme proposed 1037:1044 arg1 method 1046:1051 the proposed method 1033:1051 the proposed method 1033:1051 We compared the proposed method with existing PTM prediction methods. 28462053 7 43 theme experimental 1095:1106 arg1 results 1108:1114 The experimental results 1091:1114 The experimental results 1091:1114 The experimental results revealed that the proposed method performed comparable or better performance than the existing prediction methods, suggesting the feasibility of the developed kernels and the usefulness of the proposed method in PTM sites prediction. 28462053 4 44 theme sequence 740:747 arg1 information 749:759 local sequence information 734:759 local sequence information 734:759 To largely make use of local sequence information and site-modification relationships, we developed a local sequence kernel and Gaussian interaction profile kernel, respectively. 28462053 0 45 theme multiple 58:65 arg1 machine 89:95 multiple kernel support vector machine 58:95 multiple kernel support vector machine 58:95 Prediction of post-translational modification sites using multiple kernel support vector machine. 28462053 3 46 theme PTM 612:614 arg1 sites 616:620 PTM sites 612:620 PTM sites including phosphorylation, O-linked glycosylation, acetylation, sulfation and nitration 612:708 Here we proposed a novel computational method by using the combination of multiple kernel support vector machines (SVM) for predicting PTM sites including phosphorylation, O-linked glycosylation, acetylation, sulfation and nitration. 28462053 3 46 theme PTM 612:614 arg1 acetylation 673:683 acetylation 673:683 acetylation 673:683 Here we proposed a novel computational method by using the combination of multiple kernel support vector machines (SVM) for predicting PTM sites including phosphorylation, O-linked glycosylation, acetylation, sulfation and nitration. 28462053 3 46 theme PTM 612:614 arg1 sulfation 686:694 sulfation 686:694 sulfation 686:694 Here we proposed a novel computational method by using the combination of multiple kernel support vector machines (SVM) for predicting PTM sites including phosphorylation, O-linked glycosylation, acetylation, sulfation and nitration. 28462053 3 46 theme PTM 612:614 arg1 phosphorylation 632:646 phosphorylation 632:646 phosphorylation 632:646 Here we proposed a novel computational method by using the combination of multiple kernel support vector machines (SVM) for predicting PTM sites including phosphorylation, O-linked glycosylation, acetylation, sulfation and nitration. 28462053 3 46 theme PTM 612:614 arg1 glycosylation 658:670 O-linked glycosylation 649:670 O-linked glycosylation 649:670 Here we proposed a novel computational method by using the combination of multiple kernel support vector machines (SVM) for predicting PTM sites including phosphorylation, O-linked glycosylation, acetylation, sulfation and nitration. 28462053 3 46 theme PTM 612:614 arg1 nitration 700:708 nitration 700:708 nitration 700:708 Here we proposed a novel computational method by using the combination of multiple kernel support vector machines (SVM) for predicting PTM sites including phosphorylation, O-linked glycosylation, acetylation, sulfation and nitration. 28462053 4 47 theme local 734:738 arg1 information 749:759 local sequence information 734:759 local sequence information 734:759 To largely make use of local sequence information and site-modification relationships, we developed a local sequence kernel and Gaussian interaction profile kernel, respectively. 28462053 4 48 theme Gaussian 839:846 arg1 kernel 868:873 Gaussian interaction profile kernel 839:873 Gaussian interaction profile kernel 839:873 To largely make use of local sequence information and site-modification relationships, we developed a local sequence kernel and Gaussian interaction profile kernel, respectively. 28462053 3 49 theme O-linked 649:656 arg1 glycosylation 658:670 O-linked glycosylation 649:670 O-linked glycosylation 649:670 Here we proposed a novel computational method by using the combination of multiple kernel support vector machines (SVM) for predicting PTM sites including phosphorylation, O-linked glycosylation, acetylation, sulfation and nitration. 28462053 2 50 theme identification 288:301 arg1 high-cost 242:250 high-cost 242:250 high-cost 242:250 Considering the high-cost and labor-intensive of experimental identification, many computational prediction methods are currently available for the prediction of PTM sites by using protein local sequence information in the context of conserved motif. 28462053 4 51 theme profile 860:866 arg1 kernel 868:873 Gaussian interaction profile kernel 839:873 Gaussian interaction profile kernel 839:873 To largely make use of local sequence information and site-modification relationships, we developed a local sequence kernel and Gaussian interaction profile kernel, respectively. 28462053 3 52 theme computational 502:514 arg1 method 516:521 a novel computational method 494:521 a novel computational method 494:521 Here we proposed a novel computational method by using the combination of multiple kernel support vector machines (SVM) for predicting PTM sites including phosphorylation, O-linked glycosylation, acetylation, sulfation and nitration. 28462053 4 53 theme sequence 819:826 arg1 kernel 828:833 a local sequence kernel 811:833 a local sequence kernel 811:833 To largely make use of local sequence information and site-modification relationships, we developed a local sequence kernel and Gaussian interaction profile kernel, respectively. 28462053 2 54 theme experimental 275:286 arg1 identification 288:301 experimental identification 275:301 experimental identification 275:301 Considering the high-cost and labor-intensive of experimental identification, many computational prediction methods are currently available for the prediction of PTM sites by using protein local sequence information in the context of conserved motif. 28462053 4 55 theme information 749:759 arg1 use 727:729 use 727:729 use of local sequence information and site-modification relationships 727:795 To largely make use of local sequence information and site-modification relationships, we developed a local sequence kernel and Gaussian interaction profile kernel, respectively. 28462053 0 56 theme vector 82:87 arg1 machine 89:95 multiple kernel support vector machine 58:95 multiple kernel support vector machine 58:95 Prediction of post-translational modification sites using multiple kernel support vector machine. 28462053 4 57 theme interaction 848:858 arg1 kernel 868:873 Gaussian interaction profile kernel 839:873 Gaussian interaction profile kernel 839:873 To largely make use of local sequence information and site-modification relationships, we developed a local sequence kernel and Gaussian interaction profile kernel, respectively. 28462053 1 58 theme important 150:158 arg1 mechanism 160:168 an important mechanism 147:168 an important mechanism that is involved in the regulation of protein function 147:223 Protein post-translational modification (PTM) is an important mechanism that is involved in the regulation of protein function. 28462053 1 58 theme important 150:158 arg1 modification 125:136 Protein post-translational modification 98:136 Protein post-translational modification (PTM) 98:142 Protein post-translational modification (PTM) is an important mechanism that is involved in the regulation of protein function. 28462053 0 59 theme support 74:80 arg1 machine 89:95 multiple kernel support vector machine 58:95 multiple kernel support vector machine 58:95 Prediction of post-translational modification sites using multiple kernel support vector machine. 28462053 3 60 theme vector 575:580 arg1 SVM 592:594 SVM 592:594 SVM 592:594 Here we proposed a novel computational method by using the combination of multiple kernel support vector machines (SVM) for predicting PTM sites including phosphorylation, O-linked glycosylation, acetylation, sulfation and nitration. 28462053 3 60 theme vector 575:580 arg1 machines 582:589 multiple kernel support vector machines 551:589 multiple kernel support vector machines (SVM) 551:595 Here we proposed a novel computational method by using the combination of multiple kernel support vector machines (SVM) for predicting PTM sites including phosphorylation, O-linked glycosylation, acetylation, sulfation and nitration. 28462053 0 61 theme post-translational 14:31 arg1 sites 46:50 post-translational modification sites 14:50 post-translational modification sites 14:50 Prediction of post-translational modification sites using multiple kernel support vector machine. 28462053 3 62 theme multiple 551:558 arg1 SVM 592:594 SVM 592:594 SVM 592:594 Here we proposed a novel computational method by using the combination of multiple kernel support vector machines (SVM) for predicting PTM sites including phosphorylation, O-linked glycosylation, acetylation, sulfation and nitration. 28462053 3 62 theme multiple 551:558 arg1 machines 582:589 multiple kernel support vector machines 551:589 multiple kernel support vector machines (SVM) 551:595 Here we proposed a novel computational method by using the combination of multiple kernel support vector machines (SVM) for predicting PTM sites including phosphorylation, O-linked glycosylation, acetylation, sulfation and nitration. 28462053 7 63 theme PTM 1328:1330 arg1 sites 1332:1336 PTM sites 1328:1336 PTM sites prediction 1328:1347 The experimental results revealed that the proposed method performed comparable or better performance than the existing prediction methods, suggesting the feasibility of the developed kernels and the usefulness of the proposed method in PTM sites prediction. 27935279 0 0 theme Proteins 102:109 arg1 Engineering 75:85 Unexpected Metabolic Engineering 54:85 Unexpected Metabolic Engineering of Cytoplasmic Proteins with 2-Azido-2-deoxy-glucose 54:138 Catalytic Promiscuity of O-GlcNAc Transferase Enables Unexpected Metabolic Engineering of Cytoplasmic Proteins with 2-Azido-2-deoxy-glucose. 27935279 7 1 theme O-GlcNAc 1213:1220 arg1 modification 1222:1233 the O-GlcNAc modification 1209:1233 the O-GlcNAc modification 1209:1233 We anticipate that AcGlcAz will prove to be a useful tool to study the O-GlcNAc modification. 27935279 2 2 theme sugar 405:409 arg1 N-acetylglucosamine 448:466 uridine diphosphate N-acetylglucosamine 428:466 uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) 428:479 OGT shows surprising tolerance for structural changes in the sugar component of its nucleotide sugar donor substrate, uridine diphosphate N-acetylglucosamine (UDP-GlcNAc). 27935279 2 2 theme sugar 405:409 arg1 substrate 417:425 its nucleotide sugar donor substrate 390:425 its nucleotide sugar donor substrate 390:425 OGT shows surprising tolerance for structural changes in the sugar component of its nucleotide sugar donor substrate, uridine diphosphate N-acetylglucosamine (UDP-GlcNAc). 27935279 1 3 theme multicellular 284:296 arg1 eukaryotes 298:307 multicellular eukaryotes 284:307 multicellular eukaryotes 284:307 O-GlcNAc transferase (OGT) catalyzes the installation of N-acetylglucosamine (GlcNAc) O-linked to nucleocytoplasmic proteins (O-GlcNAc) within multicellular eukaryotes. 27935279 0 4 theme Cytoplasmic 90:100 arg1 Proteins 102:109 Cytoplasmic Proteins 90:109 Cytoplasmic Proteins with 2-Azido-2-deoxy-glucose 90:138 Catalytic Promiscuity of O-GlcNAc Transferase Enables Unexpected Metabolic Engineering of Cytoplasmic Proteins with 2-Azido-2-deoxy-glucose. 27935279 0 5 with Proteins 102:109 arg1 2-Azido-2-deoxy-glucose 116:138 2-Azido-2-deoxy-glucose 116:138 2-Azido-2-deoxy-glucose 116:138 Catalytic Promiscuity of O-GlcNAc Transferase Enables Unexpected Metabolic Engineering of Cytoplasmic Proteins with 2-Azido-2-deoxy-glucose. 27935279 2 6 theme nucleotide 394:403 arg1 N-acetylglucosamine 448:466 uridine diphosphate N-acetylglucosamine 428:466 uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) 428:479 OGT shows surprising tolerance for structural changes in the sugar component of its nucleotide sugar donor substrate, uridine diphosphate N-acetylglucosamine (UDP-GlcNAc). 27935279 2 6 theme nucleotide 394:403 arg1 substrate 417:425 its nucleotide sugar donor substrate 390:425 its nucleotide sugar donor substrate 390:425 OGT shows surprising tolerance for structural changes in the sugar component of its nucleotide sugar donor substrate, uridine diphosphate N-acetylglucosamine (UDP-GlcNAc). 27935279 1 7 link O-linked 227:234 arg1 GlcNAc 219:224 GlcNAc 219:224 GlcNAc 219:224 O-GlcNAc transferase (OGT) catalyzes the installation of N-acetylglucosamine (GlcNAc) O-linked to nucleocytoplasmic proteins (O-GlcNAc) within multicellular eukaryotes. 27935279 1 7 link O-linked 227:234 arg1 N-acetylglucosamine 198:216 N-acetylglucosamine 198:216 N-acetylglucosamine (GlcNAc) O-linked to nucleocytoplasmic proteins (O-GlcNAc) 198:275 O-GlcNAc transferase (OGT) catalyzes the installation of N-acetylglucosamine (GlcNAc) O-linked to nucleocytoplasmic proteins (O-GlcNAc) within multicellular eukaryotes. 27935279 1 7 link O-linked 227:234 arg1 O-GlcNAc 267:274 O-GlcNAc 267:274 O-GlcNAc 267:274 O-GlcNAc transferase (OGT) catalyzes the installation of N-acetylglucosamine (GlcNAc) O-linked to nucleocytoplasmic proteins (O-GlcNAc) within multicellular eukaryotes. 27935279 5 8 theme proteins 923:930 arg1 modification 883:894 OGT-dependent modification 869:894 OGT-dependent modification of nuclear and cytoplasmic proteins with O-GlcAz 869:943 Further, feeding cells with per-O-acetyl GlcAz (AcGlcAz), in combination with inhibition or inducible knockout of OGT, shows OGT-dependent modification of nuclear and cytoplasmic proteins with O-GlcAz as detected using microscopy, immunoblot, and proteomics. 27935279 2 9 theme structural 345:354 arg1 changes 356:362 structural changes 345:362 structural changes in the sugar component of its nucleotide sugar donor substrate, uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) 345:479 OGT shows surprising tolerance for structural changes in the sugar component of its nucleotide sugar donor substrate, uridine diphosphate N-acetylglucosamine (UDP-GlcNAc). 27935279 5 10 with proteins 923:930 arg1 O-GlcAz 937:943 O-GlcAz 937:943 O-GlcAz 937:943 Further, feeding cells with per-O-acetyl GlcAz (AcGlcAz), in combination with inhibition or inducible knockout of OGT, shows OGT-dependent modification of nuclear and cytoplasmic proteins with O-GlcAz as detected using microscopy, immunoblot, and proteomics. 27935279 5 11 theme per-O-acetyl 772:783 arg1 AcGlcAz 792:798 AcGlcAz 792:798 AcGlcAz 792:798 Further, feeding cells with per-O-acetyl GlcAz (AcGlcAz), in combination with inhibition or inducible knockout of OGT, shows OGT-dependent modification of nuclear and cytoplasmic proteins with O-GlcAz as detected using microscopy, immunoblot, and proteomics. 27935279 5 11 theme per-O-acetyl 772:783 arg1 GlcAz 785:789 per-O-acetyl GlcAz 772:789 per-O-acetyl GlcAz (AcGlcAz) 772:799 Further, feeding cells with per-O-acetyl GlcAz (AcGlcAz), in combination with inhibition or inducible knockout of OGT, shows OGT-dependent modification of nuclear and cytoplasmic proteins with O-GlcAz as detected using microscopy, immunoblot, and proteomics. 27935279 8 12 theme UDP-Glc 1292:1298 arg1 concentration 1275:1287 the high concentration 1266:1287 the high concentration of UDP-Glc within certain mammalian tissues 1266:1331 We also speculate that, given the high concentration of UDP-Glc within certain mammalian tissues, O-Glc may exist within mammals and serve as a physiologically relevant modification. 27935279 6 13 theme cellular 1072:1079 arg1 enzyme 1081:1086 an unidentified cellular enzyme 1056:1086 an unidentified cellular enzyme 1056:1086 We find that O-GlcAz is reversible within cells, and an unidentified cellular enzyme exists to cleave O-Glc that can also process O-GlcAz. 27935279 2 14 theme surprising 320:329 arg1 tolerance 331:339 surprising tolerance 320:339 surprising tolerance for structural changes in the sugar component of its nucleotide sugar donor substrate, uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) 320:479 OGT shows surprising tolerance for structural changes in the sugar component of its nucleotide sugar donor substrate, uridine diphosphate N-acetylglucosamine (UDP-GlcNAc). 27935279 5 15 theme nuclear 899:905 arg1 proteins 923:930 nuclear and cytoplasmic proteins 899:930 nuclear and cytoplasmic proteins with O-GlcAz 899:943 Further, feeding cells with per-O-acetyl GlcAz (AcGlcAz), in combination with inhibition or inducible knockout of OGT, shows OGT-dependent modification of nuclear and cytoplasmic proteins with O-GlcAz as detected using microscopy, immunoblot, and proteomics. 27935279 1 16 theme N-acetylglucosamine 198:216 arg1 installation 182:193 the installation 178:193 the installation of N-acetylglucosamine (GlcNAc) O-linked to nucleocytoplasmic proteins (O-GlcNAc) within multicellular eukaryotes 178:307 O-GlcNAc transferase (OGT) catalyzes the installation of N-acetylglucosamine (GlcNAc) O-linked to nucleocytoplasmic proteins (O-GlcNAc) within multicellular eukaryotes. 27935279 7 17 theme useful 1188:1193 arg1 tool 1195:1198 a useful tool 1186:1198 a useful tool to study the O-GlcNAc modification 1186:1233 We anticipate that AcGlcAz will prove to be a useful tool to study the O-GlcNAc modification. 27935279 7 17 theme useful 1188:1193 arg1 AcGlcAz 1161:1167 AcGlcAz 1161:1167 AcGlcAz 1161:1167 We anticipate that AcGlcAz will prove to be a useful tool to study the O-GlcNAc modification. 27935279 5 18 with combination 805:815 arg1 inhibition 822:831 inhibition 822:831 inhibition 822:831 Further, feeding cells with per-O-acetyl GlcAz (AcGlcAz), in combination with inhibition or inducible knockout of OGT, shows OGT-dependent modification of nuclear and cytoplasmic proteins with O-GlcAz as detected using microscopy, immunoblot, and proteomics. 27935279 5 18 with combination 805:815 arg1 knockout 846:853 knockout 846:853 knockout 846:853 Further, feeding cells with per-O-acetyl GlcAz (AcGlcAz), in combination with inhibition or inducible knockout of OGT, shows OGT-dependent modification of nuclear and cytoplasmic proteins with O-GlcAz as detected using microscopy, immunoblot, and proteomics. 27935279 2 19 theme diphosphate 436:446 arg1 UDP-GlcNAc 469:478 UDP-GlcNAc 469:478 UDP-GlcNAc 469:478 OGT shows surprising tolerance for structural changes in the sugar component of its nucleotide sugar donor substrate, uridine diphosphate N-acetylglucosamine (UDP-GlcNAc). 27935279 2 19 theme diphosphate 436:446 arg1 N-acetylglucosamine 448:466 uridine diphosphate N-acetylglucosamine 428:466 uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) 428:479 OGT shows surprising tolerance for structural changes in the sugar component of its nucleotide sugar donor substrate, uridine diphosphate N-acetylglucosamine (UDP-GlcNAc). 27935279 2 19 theme diphosphate 436:446 arg1 substrate 417:425 its nucleotide sugar donor substrate 390:425 its nucleotide sugar donor substrate 390:425 OGT shows surprising tolerance for structural changes in the sugar component of its nucleotide sugar donor substrate, uridine diphosphate N-acetylglucosamine (UDP-GlcNAc). 27935279 2 20 theme uridine 428:434 arg1 UDP-GlcNAc 469:478 UDP-GlcNAc 469:478 UDP-GlcNAc 469:478 OGT shows surprising tolerance for structural changes in the sugar component of its nucleotide sugar donor substrate, uridine diphosphate N-acetylglucosamine (UDP-GlcNAc). 27935279 2 20 theme uridine 428:434 arg1 N-acetylglucosamine 448:466 uridine diphosphate N-acetylglucosamine 428:466 uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) 428:479 OGT shows surprising tolerance for structural changes in the sugar component of its nucleotide sugar donor substrate, uridine diphosphate N-acetylglucosamine (UDP-GlcNAc). 27935279 2 20 theme uridine 428:434 arg1 substrate 417:425 its nucleotide sugar donor substrate 390:425 its nucleotide sugar donor substrate 390:425 OGT shows surprising tolerance for structural changes in the sugar component of its nucleotide sugar donor substrate, uridine diphosphate N-acetylglucosamine (UDP-GlcNAc). 27935279 0 21 theme Catalytic 0:8 arg1 Promiscuity 10:20 Catalytic Promiscuity 0:20 Catalytic Promiscuity of O-GlcNAc Transferase 0:44 Catalytic Promiscuity of O-GlcNAc Transferase Enables Unexpected Metabolic Engineering of Cytoplasmic Proteins with 2-Azido-2-deoxy-glucose. 27935279 0 22 theme O-GlcNAc 25:32 arg1 Transferase 34:44 O-GlcNAc Transferase 25:44 O-GlcNAc Transferase 25:44 Catalytic Promiscuity of O-GlcNAc Transferase Enables Unexpected Metabolic Engineering of Cytoplasmic Proteins with 2-Azido-2-deoxy-glucose. 27935279 1 23 theme O-linked 227:234 arg1 GlcNAc 219:224 GlcNAc 219:224 GlcNAc 219:224 O-GlcNAc transferase (OGT) catalyzes the installation of N-acetylglucosamine (GlcNAc) O-linked to nucleocytoplasmic proteins (O-GlcNAc) within multicellular eukaryotes. 27935279 1 23 theme O-linked 227:234 arg1 N-acetylglucosamine 198:216 N-acetylglucosamine 198:216 N-acetylglucosamine (GlcNAc) O-linked to nucleocytoplasmic proteins (O-GlcNAc) 198:275 O-GlcNAc transferase (OGT) catalyzes the installation of N-acetylglucosamine (GlcNAc) O-linked to nucleocytoplasmic proteins (O-GlcNAc) within multicellular eukaryotes. 27935279 1 23 theme O-linked 227:234 arg1 O-GlcNAc 267:274 O-GlcNAc 267:274 O-GlcNAc 267:274 O-GlcNAc transferase (OGT) catalyzes the installation of N-acetylglucosamine (GlcNAc) O-linked to nucleocytoplasmic proteins (O-GlcNAc) within multicellular eukaryotes. 27935279 1 24 theme O-GlcNAc 141:148 arg1 OGT 163:165 OGT 163:165 OGT 163:165 O-GlcNAc transferase (OGT) catalyzes the installation of N-acetylglucosamine (GlcNAc) O-linked to nucleocytoplasmic proteins (O-GlcNAc) within multicellular eukaryotes. 27935279 1 24 theme O-GlcNAc 141:148 arg1 transferase 150:160 O-GlcNAc transferase 141:160 O-GlcNAc transferase (OGT) 141:166 O-GlcNAc transferase (OGT) catalyzes the installation of N-acetylglucosamine (GlcNAc) O-linked to nucleocytoplasmic proteins (O-GlcNAc) within multicellular eukaryotes. 27935279 5 25 theme cytoplasmic 911:921 arg1 proteins 923:930 nuclear and cytoplasmic proteins 899:930 nuclear and cytoplasmic proteins with O-GlcAz 899:943 Further, feeding cells with per-O-acetyl GlcAz (AcGlcAz), in combination with inhibition or inducible knockout of OGT, shows OGT-dependent modification of nuclear and cytoplasmic proteins with O-GlcAz as detected using microscopy, immunoblot, and proteomics. 27935279 6 26 theme unidentified 1059:1070 arg1 enzyme 1081:1086 an unidentified cellular enzyme 1056:1086 an unidentified cellular enzyme 1056:1086 We find that O-GlcAz is reversible within cells, and an unidentified cellular enzyme exists to cleave O-Glc that can also process O-GlcAz. 27935279 8 27 theme relevant 1396:1403 arg1 modification 1405:1416 a physiologically relevant modification 1378:1416 a physiologically relevant modification 1378:1416 We also speculate that, given the high concentration of UDP-Glc within certain mammalian tissues, O-Glc may exist within mammals and serve as a physiologically relevant modification. 27935279 8 27 theme relevant 1396:1403 arg1 O-Glc 1334:1338 O-Glc 1334:1338 O-Glc 1334:1338 We also speculate that, given the high concentration of UDP-Glc within certain mammalian tissues, O-Glc may exist within mammals and serve as a physiologically relevant modification. 27935279 1 28 theme nucleocytoplasmic 239:255 arg1 proteins 257:264 nucleocytoplasmic proteins 239:264 nucleocytoplasmic proteins 239:264 O-GlcNAc transferase (OGT) catalyzes the installation of N-acetylglucosamine (GlcNAc) O-linked to nucleocytoplasmic proteins (O-GlcNAc) within multicellular eukaryotes. 27935279 0 29 theme Transferase 34:44 arg1 Promiscuity 10:20 Catalytic Promiscuity 0:20 Catalytic Promiscuity of O-GlcNAc Transferase 0:44 Catalytic Promiscuity of O-GlcNAc Transferase Enables Unexpected Metabolic Engineering of Cytoplasmic Proteins with 2-Azido-2-deoxy-glucose. 27935279 8 30 theme mammalian 1315:1323 arg1 tissues 1325:1331 certain mammalian tissues 1307:1331 certain mammalian tissues 1307:1331 We also speculate that, given the high concentration of UDP-Glc within certain mammalian tissues, O-Glc may exist within mammals and serve as a physiologically relevant modification. 27935279 5 31 theme OGT-dependent 869:881 arg1 modification 883:894 OGT-dependent modification 869:894 OGT-dependent modification of nuclear and cytoplasmic proteins with O-GlcAz 869:943 Further, feeding cells with per-O-acetyl GlcAz (AcGlcAz), in combination with inhibition or inducible knockout of OGT, shows OGT-dependent modification of nuclear and cytoplasmic proteins with O-GlcAz as detected using microscopy, immunoblot, and proteomics. 27935279 0 32 theme Metabolic 65:73 arg1 Engineering 75:85 Unexpected Metabolic Engineering 54:85 Unexpected Metabolic Engineering of Cytoplasmic Proteins with 2-Azido-2-deoxy-glucose 54:138 Catalytic Promiscuity of O-GlcNAc Transferase Enables Unexpected Metabolic Engineering of Cytoplasmic Proteins with 2-Azido-2-deoxy-glucose. 27935279 5 33 with cells 761:765 arg1 AcGlcAz 792:798 AcGlcAz 792:798 AcGlcAz 792:798 Further, feeding cells with per-O-acetyl GlcAz (AcGlcAz), in combination with inhibition or inducible knockout of OGT, shows OGT-dependent modification of nuclear and cytoplasmic proteins with O-GlcAz as detected using microscopy, immunoblot, and proteomics. 27935279 5 33 with cells 761:765 arg1 GlcAz 785:789 per-O-acetyl GlcAz 772:789 per-O-acetyl GlcAz (AcGlcAz) 772:799 Further, feeding cells with per-O-acetyl GlcAz (AcGlcAz), in combination with inhibition or inducible knockout of OGT, shows OGT-dependent modification of nuclear and cytoplasmic proteins with O-GlcAz as detected using microscopy, immunoblot, and proteomics. 27935279 3 34 theme O-linked 533:540 arg1 O-Glc 551:555 O-Glc 551:555 O-Glc 551:555 Here, we find that OGT uses UDP-glucose to install O-linked glucose (O-Glc) onto proteins only 25-fold less efficiently than O-GlcNAc. 27935279 3 34 theme O-linked 533:540 arg1 glucose 542:548 O-linked glucose 533:548 O-linked glucose (O-Glc) onto proteins 533:570 Here, we find that OGT uses UDP-glucose to install O-linked glucose (O-Glc) onto proteins only 25-fold less efficiently than O-GlcNAc. 27935279 0 35 theme Unexpected 54:63 arg1 Engineering 75:85 Unexpected Metabolic Engineering 54:85 Unexpected Metabolic Engineering of Cytoplasmic Proteins with 2-Azido-2-deoxy-glucose 54:138 Catalytic Promiscuity of O-GlcNAc Transferase Enables Unexpected Metabolic Engineering of Cytoplasmic Proteins with 2-Azido-2-deoxy-glucose. 27935279 3 36 link O-linked 533:540 arg1 O-Glc 551:555 O-Glc 551:555 O-Glc 551:555 Here, we find that OGT uses UDP-glucose to install O-linked glucose (O-Glc) onto proteins only 25-fold less efficiently than O-GlcNAc. 27935279 3 36 link O-linked 533:540 arg1 glucose 542:548 O-linked glucose 533:548 O-linked glucose (O-Glc) onto proteins 533:570 Here, we find that OGT uses UDP-glucose to install O-linked glucose (O-Glc) onto proteins only 25-fold less efficiently than O-GlcNAc. 27935279 8 37 theme certain 1307:1313 arg1 tissues 1325:1331 certain mammalian tissues 1307:1331 certain mammalian tissues 1307:1331 We also speculate that, given the high concentration of UDP-Glc within certain mammalian tissues, O-Glc may exist within mammals and serve as a physiologically relevant modification. 27935279 2 38 theme sugar 371:375 arg1 component 377:385 the sugar component 367:385 the sugar component of its nucleotide sugar donor substrate, uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) 367:479 OGT shows surprising tolerance for structural changes in the sugar component of its nucleotide sugar donor substrate, uridine diphosphate N-acetylglucosamine (UDP-GlcNAc). 27935279 8 39 theme high 1270:1273 arg1 concentration 1275:1287 the high concentration 1266:1287 the high concentration of UDP-Glc within certain mammalian tissues 1266:1331 We also speculate that, given the high concentration of UDP-Glc within certain mammalian tissues, O-Glc may exist within mammals and serve as a physiologically relevant modification. 27935279 5 40 theme OGT 858:860 arg1 inhibition 822:831 inhibition 822:831 inhibition 822:831 Further, feeding cells with per-O-acetyl GlcAz (AcGlcAz), in combination with inhibition or inducible knockout of OGT, shows OGT-dependent modification of nuclear and cytoplasmic proteins with O-GlcAz as detected using microscopy, immunoblot, and proteomics. 27935279 2 41 theme substrate 417:425 arg1 component 377:385 the sugar component 367:385 the sugar component of its nucleotide sugar donor substrate, uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) 367:479 OGT shows surprising tolerance for structural changes in the sugar component of its nucleotide sugar donor substrate, uridine diphosphate N-acetylglucosamine (UDP-GlcNAc). 27935279 2 42 theme donor 411:415 arg1 N-acetylglucosamine 448:466 uridine diphosphate N-acetylglucosamine 428:466 uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) 428:479 OGT shows surprising tolerance for structural changes in the sugar component of its nucleotide sugar donor substrate, uridine diphosphate N-acetylglucosamine (UDP-GlcNAc). 27935279 2 42 theme donor 411:415 arg1 substrate 417:425 its nucleotide sugar donor substrate 390:425 its nucleotide sugar donor substrate 390:425 OGT shows surprising tolerance for structural changes in the sugar component of its nucleotide sugar donor substrate, uridine diphosphate N-acetylglucosamine (UDP-GlcNAc). 27935279 2 43 from changes 356:362 arg1 component 377:385 the sugar component 367:385 the sugar component of its nucleotide sugar donor substrate, uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) 367:479 OGT shows surprising tolerance for structural changes in the sugar component of its nucleotide sugar donor substrate, uridine diphosphate N-acetylglucosamine (UDP-GlcNAc). 27676224 13 0 theme Mtb 1824:1826 arg1 values 1832:1837 Mtb MIC values 1824:1837 Mtb MIC values of 3-12 μg/mL 1824:1851 The most potent compounds have Mtb MIC values of 3-12 μg/mL. 27676224 5 1 theme tuberculosis 684:695 arg1 tuberculosis 647:658 Mycobacterium tuberculosis 633:658 Mycobacterium tuberculosis 633:658 Mycobacterium tuberculosis, the causative agent of tuberculosis, and Yersinia pestis, resulting in the plague or "black death", both rely on the MEP pathway for isoprene production. 27676224 5 1 theme tuberculosis 684:695 arg1 agent 675:679 the causative agent 661:679 the causative agent of tuberculosis 661:695 Mycobacterium tuberculosis, the causative agent of tuberculosis, and Yersinia pestis, resulting in the plague or "black death", both rely on the MEP pathway for isoprene production. 27676224 10 2 theme likely 1513:1518 arg1 reflection 1522:1531 likely a reflection 1513:1531 likely a reflection of inadequate permeability 1513:1558 In bacterial growth inhibition assays, the phosphonic acids generally resulted in poor antibacterial activity, likely a reflection of inadequate permeability. 27676224 5 3 theme causative 665:673 arg1 tuberculosis 647:658 Mycobacterium tuberculosis 633:658 Mycobacterium tuberculosis 633:658 Mycobacterium tuberculosis, the causative agent of tuberculosis, and Yersinia pestis, resulting in the plague or "black death", both rely on the MEP pathway for isoprene production. 27676224 5 3 theme causative 665:673 arg1 agent 675:679 the causative agent 661:679 the causative agent of tuberculosis 661:695 Mycobacterium tuberculosis, the causative agent of tuberculosis, and Yersinia pestis, resulting in the plague or "black death", both rely on the MEP pathway for isoprene production. 27676224 3 4 theme essential 516:524 arg1 pathway 459:465 The methylerythritol phosphate (MEP) pathway 422:465 The methylerythritol phosphate (MEP) pathway to make isoprene units 422:488 The methylerythritol phosphate (MEP) pathway to make isoprene units is a biosynthetic pathway essential to many bacteria. 27676224 3 4 theme essential 516:524 arg1 pathway 508:514 a biosynthetic pathway 493:514 a biosynthetic pathway essential to many bacteria 493:541 The methylerythritol phosphate (MEP) pathway to make isoprene units is a biosynthetic pathway essential to many bacteria. 27676224 1 5 theme bacteria 249:256 arg1 bacteria 249:256 bacteria 249:256 bacteria 249:256 Despite continued research efforts, the threat of drug resistance from a variety of bacteria continues to plague clinical communities. 27676224 1 5 theme bacteria 249:256 arg1 variety 238:244 a variety 236:244 a variety of bacteria 236:256 Despite continued research efforts, the threat of drug resistance from a variety of bacteria continues to plague clinical communities. 27676224 0 6 from pestis 157:162 arg1 Inhibitors 94:103 Inhibitors 94:103 Inhibitors of Dxr from Mycobacterium tuberculosis and Yersinia pestis 94:162 Structure-Activity Relationships of the MEPicides: N-Acyl and O-Linked Analogs of FR900098 as Inhibitors of Dxr from Mycobacterium tuberculosis and Yersinia pestis. 27676224 0 6 from pestis 157:162 arg1 Dxr 108:110 Dxr 108:110 Dxr from Mycobacterium tuberculosis and Yersinia pestis 108:162 Structure-Activity Relationships of the MEPicides: N-Acyl and O-Linked Analogs of FR900098 as Inhibitors of Dxr from Mycobacterium tuberculosis and Yersinia pestis. 27676224 6 7 theme first 883:887 arg1 step 899:902 the first committed step 879:902 the first committed step in the MEP pathway 879:921 1-Deoxy-d-xylulose 5-phosphate reductoisomerase (Dxr) catalyzes the first committed step in the MEP pathway. 27676224 12 8 theme antitubercular 1766:1779 arg1 activities 1781:1790 significantly improved antitubercular activities 1743:1790 significantly improved antitubercular activities 1743:1790 While the added lipophilicity did not enhance Yersinia activity, the compounds showed significantly improved antitubercular activities. 27676224 10 9 theme inadequate 1536:1545 arg1 permeability 1547:1558 inadequate permeability 1536:1558 inadequate permeability 1536:1558 In bacterial growth inhibition assays, the phosphonic acids generally resulted in poor antibacterial activity, likely a reflection of inadequate permeability. 27676224 1 10 theme research 183:190 arg1 efforts 192:198 continued research efforts 173:198 continued research efforts 173:198 Despite continued research efforts, the threat of drug resistance from a variety of bacteria continues to plague clinical communities. 27676224 13 11 theme MIC 1828:1830 arg1 values 1832:1837 Mtb MIC values 1824:1837 Mtb MIC values of 3-12 μg/mL 1824:1851 The most potent compounds have Mtb MIC values of 3-12 μg/mL. 27676224 14 12 from Yp 1960:1961 arg1 homologues 1936:1945 Dxr homologues 1932:1945 Dxr homologues from Mtb and Yp 1932:1961 Taken together, we have uncovered two series of analogs that potently inhibit Dxr homologues from Mtb and Yp. 27676224 8 13 link O-linked 1096:1103 arg1 group 1116:1120 O-linked alkyl/aryl group 1096:1120 O-linked alkyl/aryl group 1096:1120 The compounds contain either an extended N-acyl or O-linked alkyl/aryl group and are designed to act as bisubstrate inhibitors of the enzyme. 27676224 9 14 theme IC50 1389:1392 arg1 values 1394:1399 nanomolar IC50 values 1379:1399 nanomolar IC50 values 1379:1399 While nearly all of the compounds inhibited both Mtb and Yp Dxr to some extent, compounds generally displayed more potent inhibition against the Yp homologue, with the best analogs displaying nanomolar IC50 values. 27676224 14 15 from Mtb 1952:1954 arg1 homologues 1936:1945 Dxr homologues 1932:1945 Dxr homologues from Mtb and Yp 1932:1961 Taken together, we have uncovered two series of analogs that potently inhibit Dxr homologues from Mtb and Yp. 27676224 1 16 theme drug 215:218 arg1 resistance 220:229 drug resistance 215:229 drug resistance 215:229 Despite continued research efforts, the threat of drug resistance from a variety of bacteria continues to plague clinical communities. 27676224 1 17 from variety 238:244 arg1 threat 205:210 the threat 201:210 the threat of drug resistance from a variety of bacteria 201:256 Despite continued research efforts, the threat of drug resistance from a variety of bacteria continues to plague clinical communities. 27676224 7 18 theme parent 978:983 arg1 structure 985:993 the parent structure 974:993 the parent structure of the retrohydroxamate natural product FR900098 974:1042 We examined two series of Dxr inhibitors based on the parent structure of the retrohydroxamate natural product FR900098. 27676224 7 19 theme natural 1019:1025 arg1 product 1027:1033 the retrohydroxamate natural product FR900098 998:1042 the retrohydroxamate natural product FR900098 998:1042 We examined two series of Dxr inhibitors based on the parent structure of the retrohydroxamate natural product FR900098. 27676224 9 20 theme Yp 1244:1245 arg1 Dxr 1247:1249 Yp Dxr 1244:1249 Yp Dxr 1244:1249 While nearly all of the compounds inhibited both Mtb and Yp Dxr to some extent, compounds generally displayed more potent inhibition against the Yp homologue, with the best analogs displaying nanomolar IC50 values. 27676224 4 21 theme pathway 594:600 arg1 agents 625:630 novel antibacterial agents 605:630 novel antibacterial agents 605:630 We and others have explored inhibitors of the MEP pathway as novel antibacterial agents. 27676224 4 21 theme pathway 594:600 arg1 inhibitors 572:581 inhibitors 572:581 inhibitors of the MEP pathway 572:600 We and others have explored inhibitors of the MEP pathway as novel antibacterial agents. 27676224 7 22 theme inhibitors 954:963 arg1 series 940:945 two series 936:945 two series of Dxr inhibitors based on the parent structure of the retrohydroxamate natural product FR900098 936:1042 We examined two series of Dxr inhibitors based on the parent structure of the retrohydroxamate natural product FR900098. 27676224 12 23 theme added 1667:1671 arg1 lipophilicity 1673:1685 the added lipophilicity 1663:1685 the added lipophilicity 1663:1685 While the added lipophilicity did not enhance Yersinia activity, the compounds showed significantly improved antitubercular activities. 27676224 10 24 theme inhibition 1422:1431 arg1 assays 1433:1438 bacterial growth inhibition assays 1405:1438 bacterial growth inhibition assays 1405:1438 In bacterial growth inhibition assays, the phosphonic acids generally resulted in poor antibacterial activity, likely a reflection of inadequate permeability. 27676224 10 25 theme bacterial 1405:1413 arg1 assays 1433:1438 bacterial growth inhibition assays 1405:1438 bacterial growth inhibition assays 1405:1438 In bacterial growth inhibition assays, the phosphonic acids generally resulted in poor antibacterial activity, likely a reflection of inadequate permeability. 27676224 15 26 theme future 2038:2043 arg1 development 2052:2062 future analog development 2038:2062 future analog development 2038:2062 These inhibitors of the MEP pathway, termed MEPicides, serve as leads for future analog development. 27676224 10 27 theme phosphonic 1445:1454 arg1 acids 1456:1460 the phosphonic acids 1441:1460 the phosphonic acids 1441:1460 In bacterial growth inhibition assays, the phosphonic acids generally resulted in poor antibacterial activity, likely a reflection of inadequate permeability. 27676224 3 28 theme MEP 454:456 arg1 pathway 508:514 a biosynthetic pathway 493:514 a biosynthetic pathway essential to many bacteria 493:541 The methylerythritol phosphate (MEP) pathway to make isoprene units is a biosynthetic pathway essential to many bacteria. 27676224 3 28 theme MEP 454:456 arg1 pathway 459:465 The methylerythritol phosphate (MEP) pathway 422:465 The methylerythritol phosphate (MEP) pathway to make isoprene units 422:488 The methylerythritol phosphate (MEP) pathway to make isoprene units is a biosynthetic pathway essential to many bacteria. 27676224 3 29 theme phosphate 443:451 arg1 pathway 508:514 a biosynthetic pathway 493:514 a biosynthetic pathway essential to many bacteria 493:541 The methylerythritol phosphate (MEP) pathway to make isoprene units is a biosynthetic pathway essential to many bacteria. 27676224 3 29 theme phosphate 443:451 arg1 pathway 459:465 The methylerythritol phosphate (MEP) pathway 422:465 The methylerythritol phosphate (MEP) pathway to make isoprene units 422:488 The methylerythritol phosphate (MEP) pathway to make isoprene units is a biosynthetic pathway essential to many bacteria. 27676224 0 30 theme Structure-Activity 0:17 arg1 Relationships 19:31 Structure-Activity Relationships 0:31 Structure-Activity Relationships of the MEPicides: N-Acyl and O-Linked Analogs of FR900098 as Inhibitors of Dxr from Mycobacterium tuberculosis and Yersinia pestis. 0:163 Structure-Activity Relationships of the MEPicides: N-Acyl and O-Linked Analogs of FR900098 as Inhibitors of Dxr from Mycobacterium tuberculosis and Yersinia pestis. 27676224 9 31 theme potent 1302:1307 arg1 inhibition 1309:1318 more potent inhibition 1297:1318 more potent inhibition 1297:1318 While nearly all of the compounds inhibited both Mtb and Yp Dxr to some extent, compounds generally displayed more potent inhibition against the Yp homologue, with the best analogs displaying nanomolar IC50 values. 27676224 15 32 theme pathway 1992:1998 arg1 inhibitors 1970:1979 These inhibitors 1964:1979 These inhibitors 1964:1979 These inhibitors of the MEP pathway, termed MEPicides, serve as leads for future analog development. 27676224 5 33 theme isoprene 794:801 arg1 production 803:812 isoprene production 794:812 isoprene production 794:812 Mycobacterium tuberculosis, the causative agent of tuberculosis, and Yersinia pestis, resulting in the plague or "black death", both rely on the MEP pathway for isoprene production. 27676224 0 34 theme O-Linked 62:69 arg1 Analogs 71:77 N-Acyl and O-Linked Analogs 51:77 Structure-Activity Relationships of the MEPicides: N-Acyl and O-Linked Analogs of FR900098 as Inhibitors of Dxr from Mycobacterium tuberculosis and Yersinia pestis. 0:163 Structure-Activity Relationships of the MEPicides: N-Acyl and O-Linked Analogs of FR900098 as Inhibitors of Dxr from Mycobacterium tuberculosis and Yersinia pestis. 27676224 13 35 theme μg/mL 1847:1851 arg1 values 1832:1837 Mtb MIC values 1824:1837 Mtb MIC values of 3-12 μg/mL 1824:1851 The most potent compounds have Mtb MIC values of 3-12 μg/mL. 27676224 0 36 theme MEPicides 40:48 arg1 Relationships 19:31 Structure-Activity Relationships 0:31 Structure-Activity Relationships of the MEPicides: N-Acyl and O-Linked Analogs of FR900098 as Inhibitors of Dxr from Mycobacterium tuberculosis and Yersinia pestis. 0:163 Structure-Activity Relationships of the MEPicides: N-Acyl and O-Linked Analogs of FR900098 as Inhibitors of Dxr from Mycobacterium tuberculosis and Yersinia pestis. 27676224 9 37 theme Yp 1332:1333 arg1 homologue 1335:1343 the Yp homologue 1328:1343 the Yp homologue 1328:1343 While nearly all of the compounds inhibited both Mtb and Yp Dxr to some extent, compounds generally displayed more potent inhibition against the Yp homologue, with the best analogs displaying nanomolar IC50 values. 27676224 8 38 theme extended 1077:1084 arg1 N-acyl 1086:1091 an extended N-acyl 1074:1091 an extended N-acyl 1074:1091 The compounds contain either an extended N-acyl or O-linked alkyl/aryl group and are designed to act as bisubstrate inhibitors of the enzyme. 27676224 13 39 theme potent 1802:1807 arg1 compounds 1809:1817 The most potent compounds 1793:1817 The most potent compounds 1793:1817 The most potent compounds have Mtb MIC values of 3-12 μg/mL. 27676224 5 40 theme death 753:757 arg1 " 758:758 the plague or "black death" 732:758 " 758:758 Mycobacterium tuberculosis, the causative agent of tuberculosis, and Yersinia pestis, resulting in the plague or "black death", both rely on the MEP pathway for isoprene production. 27676224 13 41 contain have 1819:1822 arg2 values 1832:1837 Mtb MIC values 1824:1837 Mtb MIC values of 3-12 μg/mL 1824:1851 The most potent compounds have Mtb MIC values of 3-12 μg/mL. 27676224 13 41 contain have 1819:1822 arg1 compounds 1809:1817 The most potent compounds 1793:1817 The most potent compounds 1793:1817 The most potent compounds have Mtb MIC values of 3-12 μg/mL. 27676224 11 42 theme dipivaloyloxymethyl 1586:1604 arg1 esters 1620:1625 diethyl and dipivaloyloxymethyl (POM) prodrug esters 1574:1625 diethyl and dipivaloyloxymethyl (POM) prodrug esters of these compounds 1574:1644 Accordingly, diethyl and dipivaloyloxymethyl (POM) prodrug esters of these compounds were made. 27676224 0 43 theme N-Acyl 51:56 arg1 Analogs 71:77 N-Acyl and O-Linked Analogs 51:77 Structure-Activity Relationships of the MEPicides: N-Acyl and O-Linked Analogs of FR900098 as Inhibitors of Dxr from Mycobacterium tuberculosis and Yersinia pestis. 0:163 Structure-Activity Relationships of the MEPicides: N-Acyl and O-Linked Analogs of FR900098 as Inhibitors of Dxr from Mycobacterium tuberculosis and Yersinia pestis. 27676224 6 44 theme 5-phosphate 834:844 arg1 Dxr 864:866 Dxr 864:866 Dxr 864:866 1-Deoxy-d-xylulose 5-phosphate reductoisomerase (Dxr) catalyzes the first committed step in the MEP pathway. 27676224 6 44 theme 5-phosphate 834:844 arg1 reductoisomerase 846:861 1-Deoxy-d-xylulose 5-phosphate reductoisomerase 815:861 1-Deoxy-d-xylulose 5-phosphate reductoisomerase (Dxr) 815:867 1-Deoxy-d-xylulose 5-phosphate reductoisomerase (Dxr) catalyzes the first committed step in the MEP pathway. 27676224 10 45 theme antibacterial 1489:1501 arg1 activity 1503:1510 poor antibacterial activity 1484:1510 poor antibacterial activity 1484:1510 In bacterial growth inhibition assays, the phosphonic acids generally resulted in poor antibacterial activity, likely a reflection of inadequate permeability. 27676224 11 46 theme diethyl 1574:1580 arg1 esters 1620:1625 diethyl and dipivaloyloxymethyl (POM) prodrug esters 1574:1625 diethyl and dipivaloyloxymethyl (POM) prodrug esters of these compounds 1574:1644 Accordingly, diethyl and dipivaloyloxymethyl (POM) prodrug esters of these compounds were made. 27676224 2 47 theme biochemical 334:344 arg1 targets 346:352 novel biochemical targets 328:352 novel biochemical targets 328:352 Discovery and validation of novel biochemical targets will facilitate development of new drugs to combat these organisms. 27676224 1 48 theme resistance 220:229 arg1 threat 205:210 the threat 201:210 the threat of drug resistance from a variety of bacteria 201:256 Despite continued research efforts, the threat of drug resistance from a variety of bacteria continues to plague clinical communities. 27676224 8 49 theme alkyl/aryl 1105:1114 arg1 group 1116:1120 O-linked alkyl/aryl group 1096:1120 O-linked alkyl/aryl group 1096:1120 The compounds contain either an extended N-acyl or O-linked alkyl/aryl group and are designed to act as bisubstrate inhibitors of the enzyme. 27676224 14 50 theme Dxr 1932:1934 arg1 homologues 1936:1945 Dxr homologues 1932:1945 Dxr homologues from Mtb and Yp 1932:1961 Taken together, we have uncovered two series of analogs that potently inhibit Dxr homologues from Mtb and Yp. 27676224 0 51 from tuberculosis 131:142 arg1 Inhibitors 94:103 Inhibitors 94:103 Inhibitors of Dxr from Mycobacterium tuberculosis and Yersinia pestis 94:162 Structure-Activity Relationships of the MEPicides: N-Acyl and O-Linked Analogs of FR900098 as Inhibitors of Dxr from Mycobacterium tuberculosis and Yersinia pestis. 27676224 0 51 from tuberculosis 131:142 arg1 Dxr 108:110 Dxr 108:110 Dxr from Mycobacterium tuberculosis and Yersinia pestis 108:162 Structure-Activity Relationships of the MEPicides: N-Acyl and O-Linked Analogs of FR900098 as Inhibitors of Dxr from Mycobacterium tuberculosis and Yersinia pestis. 27676224 11 52 theme prodrug 1612:1618 arg1 esters 1620:1625 diethyl and dipivaloyloxymethyl (POM) prodrug esters 1574:1625 diethyl and dipivaloyloxymethyl (POM) prodrug esters of these compounds 1574:1644 Accordingly, diethyl and dipivaloyloxymethyl (POM) prodrug esters of these compounds were made. 27676224 2 53 theme new 385:387 arg1 drugs 389:393 new drugs 385:393 new drugs 385:393 Discovery and validation of novel biochemical targets will facilitate development of new drugs to combat these organisms. 27676224 14 54 theme analogs 1902:1908 arg1 series 1892:1897 two series 1888:1897 two series of analogs that potently inhibit Dxr homologues from Mtb and Yp 1888:1961 Taken together, we have uncovered two series of analogs that potently inhibit Dxr homologues from Mtb and Yp. 27676224 6 55 theme MEP 911:913 arg1 pathway 915:921 the MEP pathway 907:921 the MEP pathway 907:921 1-Deoxy-d-xylulose 5-phosphate reductoisomerase (Dxr) catalyzes the first committed step in the MEP pathway. 27676224 4 56 theme antibacterial 611:623 arg1 inhibitors 572:581 inhibitors 572:581 inhibitors of the MEP pathway 572:600 We and others have explored inhibitors of the MEP pathway as novel antibacterial agents. 27676224 4 56 theme antibacterial 611:623 arg1 agents 625:630 novel antibacterial agents 605:630 novel antibacterial agents 605:630 We and others have explored inhibitors of the MEP pathway as novel antibacterial agents. 27676224 10 57 theme a 1520:1520 arg1 reflection 1522:1531 likely a reflection 1513:1531 likely a reflection of inadequate permeability 1513:1558 In bacterial growth inhibition assays, the phosphonic acids generally resulted in poor antibacterial activity, likely a reflection of inadequate permeability. 27676224 11 58 theme compounds 1636:1644 arg1 esters 1620:1625 diethyl and dipivaloyloxymethyl (POM) prodrug esters 1574:1625 diethyl and dipivaloyloxymethyl (POM) prodrug esters of these compounds 1574:1644 Accordingly, diethyl and dipivaloyloxymethyl (POM) prodrug esters of these compounds were made. 27676224 9 59 theme nanomolar 1379:1387 arg1 values 1394:1399 nanomolar IC50 values 1379:1399 nanomolar IC50 values 1379:1399 While nearly all of the compounds inhibited both Mtb and Yp Dxr to some extent, compounds generally displayed more potent inhibition against the Yp homologue, with the best analogs displaying nanomolar IC50 values. 27676224 12 60 theme improved 1757:1764 arg1 activities 1781:1790 significantly improved antitubercular activities 1743:1790 significantly improved antitubercular activities 1743:1790 While the added lipophilicity did not enhance Yersinia activity, the compounds showed significantly improved antitubercular activities. 27676224 6 61 theme committed 889:897 arg1 step 899:902 the first committed step 879:902 the first committed step in the MEP pathway 879:921 1-Deoxy-d-xylulose 5-phosphate reductoisomerase (Dxr) catalyzes the first committed step in the MEP pathway. 27676224 4 62 theme MEP 590:592 arg1 pathway 594:600 the MEP pathway 586:600 the MEP pathway 586:600 We and others have explored inhibitors of the MEP pathway as novel antibacterial agents. 27676224 10 63 theme permeability 1547:1558 arg1 reflection 1522:1531 likely a reflection 1513:1531 likely a reflection of inadequate permeability 1513:1558 In bacterial growth inhibition assays, the phosphonic acids generally resulted in poor antibacterial activity, likely a reflection of inadequate permeability. 27676224 1 64 theme continued 173:181 arg1 efforts 192:198 continued research efforts 173:198 continued research efforts 173:198 Despite continued research efforts, the threat of drug resistance from a variety of bacteria continues to plague clinical communities. 27676224 8 65 theme bisubstrate 1149:1159 arg1 compounds 1049:1057 The compounds 1045:1057 The compounds 1045:1057 The compounds contain either an extended N-acyl or O-linked alkyl/aryl group and are designed to act as bisubstrate inhibitors of the enzyme. 27676224 8 65 theme bisubstrate 1149:1159 arg1 inhibitors 1161:1170 bisubstrate inhibitors 1149:1170 bisubstrate inhibitors of the enzyme 1149:1184 The compounds contain either an extended N-acyl or O-linked alkyl/aryl group and are designed to act as bisubstrate inhibitors of the enzyme. 27676224 15 66 theme analog 2045:2050 arg1 development 2052:2062 future analog development 2038:2062 future analog development 2038:2062 These inhibitors of the MEP pathway, termed MEPicides, serve as leads for future analog development. 27676224 5 67 dep rely 766:769 arg1 both 761:764 both 761:764 both 761:764 Mycobacterium tuberculosis, the causative agent of tuberculosis, and Yersinia pestis, resulting in the plague or "black death", both rely on the MEP pathway for isoprene production. 27676224 8 68 theme enzyme 1179:1184 arg1 compounds 1049:1057 The compounds 1045:1057 The compounds 1045:1057 The compounds contain either an extended N-acyl or O-linked alkyl/aryl group and are designed to act as bisubstrate inhibitors of the enzyme. 27676224 8 68 theme enzyme 1179:1184 arg1 inhibitors 1161:1170 bisubstrate inhibitors 1149:1170 bisubstrate inhibitors of the enzyme 1149:1184 The compounds contain either an extended N-acyl or O-linked alkyl/aryl group and are designed to act as bisubstrate inhibitors of the enzyme. 27676224 2 69 theme targets 346:352 arg1 validation 314:323 validation 314:323 validation 314:323 Discovery and validation of novel biochemical targets will facilitate development of new drugs to combat these organisms. 27676224 2 69 theme targets 346:352 arg1 Discovery 300:308 Discovery 300:308 Discovery 300:308 Discovery and validation of novel biochemical targets will facilitate development of new drugs to combat these organisms. 27676224 7 70 theme product 1027:1033 arg1 structure 985:993 the parent structure 974:993 the parent structure of the retrohydroxamate natural product FR900098 974:1042 We examined two series of Dxr inhibitors based on the parent structure of the retrohydroxamate natural product FR900098. 27676224 7 71 theme retrohydroxamate 1002:1017 arg1 product 1027:1033 the retrohydroxamate natural product FR900098 998:1042 the retrohydroxamate natural product FR900098 998:1042 We examined two series of Dxr inhibitors based on the parent structure of the retrohydroxamate natural product FR900098. 27676224 0 72 from Inhibitors 94:103 arg1 tuberculosis 131:142 Mycobacterium tuberculosis 117:142 Mycobacterium tuberculosis 117:142 Structure-Activity Relationships of the MEPicides: N-Acyl and O-Linked Analogs of FR900098 as Inhibitors of Dxr from Mycobacterium tuberculosis and Yersinia pestis. 27676224 0 72 from Inhibitors 94:103 arg1 pestis 157:162 Yersinia pestis 148:162 Yersinia pestis 148:162 Structure-Activity Relationships of the MEPicides: N-Acyl and O-Linked Analogs of FR900098 as Inhibitors of Dxr from Mycobacterium tuberculosis and Yersinia pestis. 27676224 5 73 theme black 747:751 arg1 " 758:758 the plague or "black death" 732:758 " 758:758 Mycobacterium tuberculosis, the causative agent of tuberculosis, and Yersinia pestis, resulting in the plague or "black death", both rely on the MEP pathway for isoprene production. 27676224 12 74 theme Yersinia 1703:1710 arg1 activity 1712:1719 Yersinia activity 1703:1719 Yersinia activity 1703:1719 While the added lipophilicity did not enhance Yersinia activity, the compounds showed significantly improved antitubercular activities. 27676224 0 75 theme FR900098 82:89 arg1 Analogs 71:77 N-Acyl and O-Linked Analogs 51:77 Structure-Activity Relationships of the MEPicides: N-Acyl and O-Linked Analogs of FR900098 as Inhibitors of Dxr from Mycobacterium tuberculosis and Yersinia pestis. 0:163 Structure-Activity Relationships of the MEPicides: N-Acyl and O-Linked Analogs of FR900098 as Inhibitors of Dxr from Mycobacterium tuberculosis and Yersinia pestis. 27676224 10 76 theme growth 1415:1420 arg1 assays 1433:1438 bacterial growth inhibition assays 1405:1438 bacterial growth inhibition assays 1405:1438 In bacterial growth inhibition assays, the phosphonic acids generally resulted in poor antibacterial activity, likely a reflection of inadequate permeability. 27676224 7 77 theme Dxr 950:952 arg1 inhibitors 954:963 Dxr inhibitors 950:963 Dxr inhibitors based on the parent structure of the retrohydroxamate natural product FR900098 950:1042 We examined two series of Dxr inhibitors based on the parent structure of the retrohydroxamate natural product FR900098. 27676224 0 78 theme Dxr 108:110 arg1 Inhibitors 94:103 Inhibitors 94:103 Inhibitors of Dxr from Mycobacterium tuberculosis and Yersinia pestis 94:162 Structure-Activity Relationships of the MEPicides: N-Acyl and O-Linked Analogs of FR900098 as Inhibitors of Dxr from Mycobacterium tuberculosis and Yersinia pestis. 27676224 8 79 contain contain 1059:1065 arg2 group 1116:1120 O-linked alkyl/aryl group 1096:1120 O-linked alkyl/aryl group 1096:1120 The compounds contain either an extended N-acyl or O-linked alkyl/aryl group and are designed to act as bisubstrate inhibitors of the enzyme. 27676224 8 79 contain contain 1059:1065 arg2 N-acyl 1086:1091 an extended N-acyl 1074:1091 an extended N-acyl 1074:1091 The compounds contain either an extended N-acyl or O-linked alkyl/aryl group and are designed to act as bisubstrate inhibitors of the enzyme. 27676224 8 79 contain contain 1059:1065 arg1 compounds 1049:1057 The compounds 1045:1057 The compounds 1045:1057 The compounds contain either an extended N-acyl or O-linked alkyl/aryl group and are designed to act as bisubstrate inhibitors of the enzyme. 27676224 8 79 contain contain 1059:1065 arg1 inhibitors 1161:1170 bisubstrate inhibitors 1149:1170 bisubstrate inhibitors of the enzyme 1149:1184 The compounds contain either an extended N-acyl or O-linked alkyl/aryl group and are designed to act as bisubstrate inhibitors of the enzyme. 27676224 5 80 theme MEP 778:780 arg1 pathway 782:788 the MEP pathway 774:788 the MEP pathway for isoprene production 774:812 Mycobacterium tuberculosis, the causative agent of tuberculosis, and Yersinia pestis, resulting in the plague or "black death", both rely on the MEP pathway for isoprene production. 27676224 2 81 theme drugs 389:393 arg1 development 370:380 development 370:380 development of new drugs to combat these organisms 370:419 Discovery and validation of novel biochemical targets will facilitate development of new drugs to combat these organisms. 27676224 1 82 theme clinical 278:285 arg1 communities 287:297 clinical communities 278:297 clinical communities 278:297 Despite continued research efforts, the threat of drug resistance from a variety of bacteria continues to plague clinical communities. 27676224 3 83 theme isoprene 475:482 arg1 units 484:488 isoprene units 475:488 isoprene units 475:488 The methylerythritol phosphate (MEP) pathway to make isoprene units is a biosynthetic pathway essential to many bacteria. 27676224 3 84 theme methylerythritol 426:441 arg1 pathway 508:514 a biosynthetic pathway 493:514 a biosynthetic pathway essential to many bacteria 493:541 The methylerythritol phosphate (MEP) pathway to make isoprene units is a biosynthetic pathway essential to many bacteria. 27676224 3 84 theme methylerythritol 426:441 arg1 pathway 459:465 The methylerythritol phosphate (MEP) pathway 422:465 The methylerythritol phosphate (MEP) pathway to make isoprene units 422:488 The methylerythritol phosphate (MEP) pathway to make isoprene units is a biosynthetic pathway essential to many bacteria. 27676224 15 85 theme MEP 1988:1990 arg1 pathway 1992:1998 the MEP pathway 1984:1998 the MEP pathway 1984:1998 These inhibitors of the MEP pathway, termed MEPicides, serve as leads for future analog development. 27676224 8 86 theme O-linked 1096:1103 arg1 group 1116:1120 O-linked alkyl/aryl group 1096:1120 O-linked alkyl/aryl group 1096:1120 The compounds contain either an extended N-acyl or O-linked alkyl/aryl group and are designed to act as bisubstrate inhibitors of the enzyme. 27676224 3 87 theme biosynthetic 495:506 arg1 pathway 459:465 The methylerythritol phosphate (MEP) pathway 422:465 The methylerythritol phosphate (MEP) pathway to make isoprene units 422:488 The methylerythritol phosphate (MEP) pathway to make isoprene units is a biosynthetic pathway essential to many bacteria. 27676224 3 87 theme biosynthetic 495:506 arg1 pathway 508:514 a biosynthetic pathway 493:514 a biosynthetic pathway essential to many bacteria 493:541 The methylerythritol phosphate (MEP) pathway to make isoprene units is a biosynthetic pathway essential to many bacteria. 27676224 6 88 theme 1-Deoxy-d-xylulose 815:832 arg1 Dxr 864:866 Dxr 864:866 Dxr 864:866 1-Deoxy-d-xylulose 5-phosphate reductoisomerase (Dxr) catalyzes the first committed step in the MEP pathway. 27676224 6 88 theme 1-Deoxy-d-xylulose 815:832 arg1 reductoisomerase 846:861 1-Deoxy-d-xylulose 5-phosphate reductoisomerase 815:861 1-Deoxy-d-xylulose 5-phosphate reductoisomerase (Dxr) 815:867 1-Deoxy-d-xylulose 5-phosphate reductoisomerase (Dxr) catalyzes the first committed step in the MEP pathway. 27676224 3 89 dep pathway 459:465 arg1 make 470:473 make 470:473 to make isoprene units 467:488 The methylerythritol phosphate (MEP) pathway to make isoprene units is a biosynthetic pathway essential to many bacteria. 27676224 4 90 theme novel 605:609 arg1 inhibitors 572:581 inhibitors 572:581 inhibitors of the MEP pathway 572:600 We and others have explored inhibitors of the MEP pathway as novel antibacterial agents. 27676224 4 90 theme novel 605:609 arg1 agents 625:630 novel antibacterial agents 605:630 novel antibacterial agents 605:630 We and others have explored inhibitors of the MEP pathway as novel antibacterial agents. 27676224 10 91 theme poor 1484:1487 arg1 activity 1503:1510 poor antibacterial activity 1484:1510 poor antibacterial activity 1484:1510 In bacterial growth inhibition assays, the phosphonic acids generally resulted in poor antibacterial activity, likely a reflection of inadequate permeability. 27676224 2 92 theme novel 328:332 arg1 targets 346:352 novel biochemical targets 328:352 novel biochemical targets 328:352 Discovery and validation of novel biochemical targets will facilitate development of new drugs to combat these organisms. 27676224 9 93 theme best 1355:1358 arg1 analogs 1360:1366 the best analogs 1351:1366 the best analogs displaying nanomolar IC50 values 1351:1399 While nearly all of the compounds inhibited both Mtb and Yp Dxr to some extent, compounds generally displayed more potent inhibition against the Yp homologue, with the best analogs displaying nanomolar IC50 values. 27676224 0 94 dep Relationships 19:31 arg1 Analogs 71:77 N-Acyl and O-Linked Analogs 51:77 Structure-Activity Relationships of the MEPicides: N-Acyl and O-Linked Analogs of FR900098 as Inhibitors of Dxr from Mycobacterium tuberculosis and Yersinia pestis. 0:163 Structure-Activity Relationships of the MEPicides: N-Acyl and O-Linked Analogs of FR900098 as Inhibitors of Dxr from Mycobacterium tuberculosis and Yersinia pestis. 27676224 6 95 from step 899:902 arg1 pathway 915:921 the MEP pathway 907:921 the MEP pathway 907:921 1-Deoxy-d-xylulose 5-phosphate reductoisomerase (Dxr) catalyzes the first committed step in the MEP pathway. 27676224 3 96 theme many 529:532 arg1 bacteria 534:541 many bacteria 529:541 many bacteria 529:541 The methylerythritol phosphate (MEP) pathway to make isoprene units is a biosynthetic pathway essential to many bacteria. 24082034 0 0 theme P1 77:78 arg1 determinants 80:91 multivalent O-linked blood group P1 determinants 44:91 multivalent O-linked blood group P1 determinants on mucin-type fusion proteins 44:121 Shiga-like toxin binds with high avidity to multivalent O-linked blood group P1 determinants on mucin-type fusion proteins. 24082034 1 1 theme multiple 298:305 arg1 copies 307:312 multiple copies 298:312 multiple copies of the blood group P1 determinant 298:346 The binding of Shiga-like toxin 1 (Stx1) and Shiga-like toxin 2 (Stx2) to a mucin-like fusion protein, P-selectin glycoprotein ligand-1/mouse IgG2b (PSGL-1/mIgG2b), carrying multiple copies of the blood group P1 determinant on O-glycans was investigated with western blot and the biosensor Biacore. 24082034 3 2 theme PSGL-1/mIgG2b 701:713 arg1 analyses 680:687 Western blot analyses 667:687 Western blot analyses of purified PSGL-1/mIgG2b 667:713 Western blot analyses of purified PSGL-1/mIgG2b and liquid chromatography-mass spectrometry (LC-MS) of released O-glycans confirmed the presence of the P1 determinant. 24082034 3 2 theme PSGL-1/mIgG2b 701:713 arg1 LC-MS 760:764 LC-MS 760:764 LC-MS 760:764 Western blot analyses of purified PSGL-1/mIgG2b and liquid chromatography-mass spectrometry (LC-MS) of released O-glycans confirmed the presence of the P1 determinant. 24082034 3 2 theme PSGL-1/mIgG2b 701:713 arg1 spectrometry 746:757 liquid chromatography-mass spectrometry 719:757 liquid chromatography-mass spectrometry (LC-MS) of released O-glycans 719:787 Western blot analyses of purified PSGL-1/mIgG2b and liquid chromatography-mass spectrometry (LC-MS) of released O-glycans confirmed the presence of the P1 determinant. 24082034 1 3 theme toxin 150:154 arg1 binding 128:134 The binding 124:134 The binding of Shiga-like toxin 1 (Stx1) and Shiga-like toxin 2 (Stx2) to a mucin-like fusion protein, P-selectin glycoprotein ligand-1/mouse IgG2b (PSGL-1/mIgG2b), carrying multiple copies of the blood group P1 determinant on O-glycans 124:359 The binding of Shiga-like toxin 1 (Stx1) and Shiga-like toxin 2 (Stx2) to a mucin-like fusion protein, P-selectin glycoprotein ligand-1/mouse IgG2b (PSGL-1/mIgG2b), carrying multiple copies of the blood group P1 determinant on O-glycans was investigated with western blot and the biosensor Biacore. 24082034 8 4 theme toxins 1571:1576 arg1 inhibitor 1552:1560 a potential therapeutic inhibitor 1528:1560 a potential therapeutic inhibitor of these toxins 1528:1576 P1-decorated PSGL-1/mIgG2b bound with high avidity to both Stx1 and Stx2, and as such constitutes a potential therapeutic inhibitor of these toxins. 24082034 1 5 theme mucin-like 200:209 arg1 IgG2b 266:270 P-selectin glycoprotein ligand-1/mouse IgG2b 227:270 P-selectin glycoprotein ligand-1/mouse IgG2b (PSGL-1/mIgG2b) 227:286 The binding of Shiga-like toxin 1 (Stx1) and Shiga-like toxin 2 (Stx2) to a mucin-like fusion protein, P-selectin glycoprotein ligand-1/mouse IgG2b (PSGL-1/mIgG2b), carrying multiple copies of the blood group P1 determinant on O-glycans was investigated with western blot and the biosensor Biacore. 24082034 1 5 theme mucin-like 200:209 arg1 protein 218:224 a mucin-like fusion protein 198:224 a mucin-like fusion protein 198:224 The binding of Shiga-like toxin 1 (Stx1) and Shiga-like toxin 2 (Stx2) to a mucin-like fusion protein, P-selectin glycoprotein ligand-1/mouse IgG2b (PSGL-1/mIgG2b), carrying multiple copies of the blood group P1 determinant on O-glycans was investigated with western blot and the biosensor Biacore. 24082034 0 6 theme group 71:75 arg1 determinants 80:91 multivalent O-linked blood group P1 determinants 44:91 multivalent O-linked blood group P1 determinants on mucin-type fusion proteins 44:121 Shiga-like toxin binds with high avidity to multivalent O-linked blood group P1 determinants on mucin-type fusion proteins. 24082034 3 7 theme Western 667:673 arg1 analyses 680:687 Western blot analyses 667:687 Western blot analyses of purified PSGL-1/mIgG2b 667:713 Western blot analyses of purified PSGL-1/mIgG2b and liquid chromatography-mass spectrometry (LC-MS) of released O-glycans confirmed the presence of the P1 determinant. 24082034 2 8 theme pigeon 560:565 arg1 α4Gal-T 595:601 α4Gal-T 595:601 α4Gal-T 595:601 Chinese hamster ovary K-1 (CHO-K1) cells were stably transfected with linearized plasmids encoding the PSGL-1/mIgG2b fusion protein, the pigeon α1,4-galactosyltransferase (α4Gal-T) and the core 2 β1,6-N-acetylglucosaminyltransferase (C2GnT-I). 24082034 2 8 theme pigeon 560:565 arg1 α1,4-galactosyltransferase 567:592 the pigeon α1,4-galactosyltransferase 556:592 the pigeon α1,4-galactosyltransferase (α4Gal-T) 556:602 Chinese hamster ovary K-1 (CHO-K1) cells were stably transfected with linearized plasmids encoding the PSGL-1/mIgG2b fusion protein, the pigeon α1,4-galactosyltransferase (α4Gal-T) and the core 2 β1,6-N-acetylglucosaminyltransferase (C2GnT-I). 24082034 6 9 theme Stx1 1171:1174 arg1 binding 1176:1182 the Stx1 binding 1167:1182 the Stx1 binding 1167:1182 Stx1 and Stx2 bound with high avidity to both PSGL-1/mIgG2b and P(k)-albumin, while the Stx1 binding was the strongest. 24082034 6 9 theme Stx1 1171:1174 arg1 strongest 1192:1200 strongest 1192:1200 strongest 1192:1200 Stx1 and Stx2 bound with high avidity to both PSGL-1/mIgG2b and P(k)-albumin, while the Stx1 binding was the strongest. 24082034 1 10 theme fusion 211:216 arg1 IgG2b 266:270 P-selectin glycoprotein ligand-1/mouse IgG2b 227:270 P-selectin glycoprotein ligand-1/mouse IgG2b (PSGL-1/mIgG2b) 227:286 The binding of Shiga-like toxin 1 (Stx1) and Shiga-like toxin 2 (Stx2) to a mucin-like fusion protein, P-selectin glycoprotein ligand-1/mouse IgG2b (PSGL-1/mIgG2b), carrying multiple copies of the blood group P1 determinant on O-glycans was investigated with western blot and the biosensor Biacore. 24082034 1 10 theme fusion 211:216 arg1 protein 218:224 a mucin-like fusion protein 198:224 a mucin-like fusion protein 198:224 The binding of Shiga-like toxin 1 (Stx1) and Shiga-like toxin 2 (Stx2) to a mucin-like fusion protein, P-selectin glycoprotein ligand-1/mouse IgG2b (PSGL-1/mIgG2b), carrying multiple copies of the blood group P1 determinant on O-glycans was investigated with western blot and the biosensor Biacore. 24082034 3 11 theme blot 675:678 arg1 analyses 680:687 Western blot analyses 667:687 Western blot analyses of purified PSGL-1/mIgG2b 667:713 Western blot analyses of purified PSGL-1/mIgG2b and liquid chromatography-mass spectrometry (LC-MS) of released O-glycans confirmed the presence of the P1 determinant. 24082034 4 12 theme Stx1 885:888 arg1 binding 874:880 strong binding 867:880 strong binding of Stx1, but not Stx2, to PSGL-1/mIgG2b 867:920 Western blot analysis indicated strong binding of Stx1, but not Stx2, to PSGL-1/mIgG2b. 24082034 2 13 theme core 612:615 arg1 C2GnT-I 657:663 C2GnT-I 657:663 C2GnT-I 657:663 Chinese hamster ovary K-1 (CHO-K1) cells were stably transfected with linearized plasmids encoding the PSGL-1/mIgG2b fusion protein, the pigeon α1,4-galactosyltransferase (α4Gal-T) and the core 2 β1,6-N-acetylglucosaminyltransferase (C2GnT-I). 24082034 2 13 theme core 612:615 arg1 β1,6-N-acetylglucosaminyltransferase 619:654 the core 2 β1,6-N-acetylglucosaminyltransferase 608:654 the core 2 β1,6-N-acetylglucosaminyltransferase (C2GnT-I) 608:664 Chinese hamster ovary K-1 (CHO-K1) cells were stably transfected with linearized plasmids encoding the PSGL-1/mIgG2b fusion protein, the pigeon α1,4-galactosyltransferase (α4Gal-T) and the core 2 β1,6-N-acetylglucosaminyltransferase (C2GnT-I). 24082034 8 14 theme potential 1530:1538 arg1 inhibitor 1552:1560 a potential therapeutic inhibitor 1528:1560 a potential therapeutic inhibitor of these toxins 1528:1576 P1-decorated PSGL-1/mIgG2b bound with high avidity to both Stx1 and Stx2, and as such constitutes a potential therapeutic inhibitor of these toxins. 24082034 1 15 theme biosensor 404:412 arg1 Biacore 414:420 the biosensor Biacore 400:420 the biosensor Biacore 400:420 The binding of Shiga-like toxin 1 (Stx1) and Shiga-like toxin 2 (Stx2) to a mucin-like fusion protein, P-selectin glycoprotein ligand-1/mouse IgG2b (PSGL-1/mIgG2b), carrying multiple copies of the blood group P1 determinant on O-glycans was investigated with western blot and the biosensor Biacore. 24082034 5 16 gly neoglycoprotein 1053:1067 arg1 neoglycoprotein 1053:1067 a P(k)-albumin neoglycoprotein 1038:1067 a P(k)-albumin neoglycoprotein 1038:1067 In a Biacore assay, Stx1 and Stx2 were immobilized on a dextran chip and the binding of purified PSGL-1/mIgG2b and a P(k)-albumin neoglycoprotein was analyzed. 24082034 3 17 theme P1 819:820 arg1 determinant 822:832 the P1 determinant 815:832 the P1 determinant 815:832 Western blot analyses of purified PSGL-1/mIgG2b and liquid chromatography-mass spectrometry (LC-MS) of released O-glycans confirmed the presence of the P1 determinant. 24082034 0 18 theme fusion 107:112 arg1 proteins 114:121 mucin-type fusion proteins 96:121 mucin-type fusion proteins 96:121 Shiga-like toxin binds with high avidity to multivalent O-linked blood group P1 determinants on mucin-type fusion proteins. 24082034 1 19 theme blood 321:325 arg1 determinant 336:346 the blood group P1 determinant 317:346 the blood group P1 determinant 317:346 The binding of Shiga-like toxin 1 (Stx1) and Shiga-like toxin 2 (Stx2) to a mucin-like fusion protein, P-selectin glycoprotein ligand-1/mouse IgG2b (PSGL-1/mIgG2b), carrying multiple copies of the blood group P1 determinant on O-glycans was investigated with western blot and the biosensor Biacore. 24082034 4 20 theme blot 843:846 arg1 analysis 848:855 Western blot analysis 835:855 Western blot analysis 835:855 Western blot analysis indicated strong binding of Stx1, but not Stx2, to PSGL-1/mIgG2b. 24082034 7 21 theme core 1312:1315 arg1 enzyme 1319:1324 the core 2 enzyme 1308:1324 the core 2 enzyme 1308:1324 In summary, we have shown that the pigeon α4Gal-T can be aberrantly expressed in CHO cells together with the core 2 enzyme to generate multiple, O-linked P1 determinants on a simultaneously expressed mucin-type fusion protein. 24082034 7 22 dep multiple 1338:1345 arg1 O-linked 1348:1355 O-linked 1348:1355 O-linked 1348:1355 In summary, we have shown that the pigeon α4Gal-T can be aberrantly expressed in CHO cells together with the core 2 enzyme to generate multiple, O-linked P1 determinants on a simultaneously expressed mucin-type fusion protein. 24082034 0 23 theme mucin-type 96:105 arg1 proteins 114:121 mucin-type fusion proteins 96:121 mucin-type fusion proteins 96:121 Shiga-like toxin binds with high avidity to multivalent O-linked blood group P1 determinants on mucin-type fusion proteins. 24082034 1 24 theme group 327:331 arg1 determinant 336:346 the blood group P1 determinant 317:346 the blood group P1 determinant 317:346 The binding of Shiga-like toxin 1 (Stx1) and Shiga-like toxin 2 (Stx2) to a mucin-like fusion protein, P-selectin glycoprotein ligand-1/mouse IgG2b (PSGL-1/mIgG2b), carrying multiple copies of the blood group P1 determinant on O-glycans was investigated with western blot and the biosensor Biacore. 24082034 3 25 theme determinant 822:832 arg1 presence 803:810 the presence 799:810 the presence of the P1 determinant 799:832 Western blot analyses of purified PSGL-1/mIgG2b and liquid chromatography-mass spectrometry (LC-MS) of released O-glycans confirmed the presence of the P1 determinant. 24082034 6 26 theme high 1108:1111 arg1 avidity 1113:1119 high avidity 1108:1119 high avidity 1108:1119 Stx1 and Stx2 bound with high avidity to both PSGL-1/mIgG2b and P(k)-albumin, while the Stx1 binding was the strongest. 24082034 7 27 theme multiple 1338:1345 arg1 determinants 1360:1371 multiple, O-linked P1 determinants 1338:1371 multiple, O-linked P1 determinants on a simultaneously expressed mucin-type fusion protein 1338:1427 In summary, we have shown that the pigeon α4Gal-T can be aberrantly expressed in CHO cells together with the core 2 enzyme to generate multiple, O-linked P1 determinants on a simultaneously expressed mucin-type fusion protein. 24082034 1 28 theme P1 333:334 arg1 determinant 336:346 the blood group P1 determinant 317:346 the blood group P1 determinant 317:346 The binding of Shiga-like toxin 1 (Stx1) and Shiga-like toxin 2 (Stx2) to a mucin-like fusion protein, P-selectin glycoprotein ligand-1/mouse IgG2b (PSGL-1/mIgG2b), carrying multiple copies of the blood group P1 determinant on O-glycans was investigated with western blot and the biosensor Biacore. 24082034 3 29 theme liquid 719:724 arg1 LC-MS 760:764 LC-MS 760:764 LC-MS 760:764 Western blot analyses of purified PSGL-1/mIgG2b and liquid chromatography-mass spectrometry (LC-MS) of released O-glycans confirmed the presence of the P1 determinant. 24082034 3 29 theme liquid 719:724 arg1 spectrometry 746:757 liquid chromatography-mass spectrometry 719:757 liquid chromatography-mass spectrometry (LC-MS) of released O-glycans 719:787 Western blot analyses of purified PSGL-1/mIgG2b and liquid chromatography-mass spectrometry (LC-MS) of released O-glycans confirmed the presence of the P1 determinant. 24082034 0 30 theme Shiga-like 0:9 arg1 toxin 11:15 Shiga-like toxin 0:15 Shiga-like toxin 0:15 Shiga-like toxin binds with high avidity to multivalent O-linked blood group P1 determinants on mucin-type fusion proteins. 24082034 1 31 theme P-selectin 227:236 arg1 PSGL-1/mIgG2b 273:285 PSGL-1/mIgG2b 273:285 PSGL-1/mIgG2b 273:285 The binding of Shiga-like toxin 1 (Stx1) and Shiga-like toxin 2 (Stx2) to a mucin-like fusion protein, P-selectin glycoprotein ligand-1/mouse IgG2b (PSGL-1/mIgG2b), carrying multiple copies of the blood group P1 determinant on O-glycans was investigated with western blot and the biosensor Biacore. 24082034 1 31 theme P-selectin 227:236 arg1 IgG2b 266:270 P-selectin glycoprotein ligand-1/mouse IgG2b 227:270 P-selectin glycoprotein ligand-1/mouse IgG2b (PSGL-1/mIgG2b) 227:286 The binding of Shiga-like toxin 1 (Stx1) and Shiga-like toxin 2 (Stx2) to a mucin-like fusion protein, P-selectin glycoprotein ligand-1/mouse IgG2b (PSGL-1/mIgG2b), carrying multiple copies of the blood group P1 determinant on O-glycans was investigated with western blot and the biosensor Biacore. 24082034 1 31 theme P-selectin 227:236 arg1 protein 218:224 a mucin-like fusion protein 198:224 a mucin-like fusion protein 198:224 The binding of Shiga-like toxin 1 (Stx1) and Shiga-like toxin 2 (Stx2) to a mucin-like fusion protein, P-selectin glycoprotein ligand-1/mouse IgG2b (PSGL-1/mIgG2b), carrying multiple copies of the blood group P1 determinant on O-glycans was investigated with western blot and the biosensor Biacore. 24082034 5 32 theme PSGL-1/mIgG2b 1020:1032 arg1 binding 1000:1006 the binding 996:1006 the binding of purified PSGL-1/mIgG2b 996:1032 In a Biacore assay, Stx1 and Stx2 were immobilized on a dextran chip and the binding of purified PSGL-1/mIgG2b and a P(k)-albumin neoglycoprotein was analyzed. 24082034 5 32 theme PSGL-1/mIgG2b 1020:1032 arg1 neoglycoprotein 1053:1067 a P(k)-albumin neoglycoprotein 1038:1067 a P(k)-albumin neoglycoprotein 1038:1067 In a Biacore assay, Stx1 and Stx2 were immobilized on a dextran chip and the binding of purified PSGL-1/mIgG2b and a P(k)-albumin neoglycoprotein was analyzed. 24082034 4 33 theme strong 867:872 arg1 binding 874:880 strong binding 867:880 strong binding of Stx1, but not Stx2, to PSGL-1/mIgG2b 867:920 Western blot analysis indicated strong binding of Stx1, but not Stx2, to PSGL-1/mIgG2b. 24082034 1 34 theme glycoprotein 238:249 arg1 PSGL-1/mIgG2b 273:285 PSGL-1/mIgG2b 273:285 PSGL-1/mIgG2b 273:285 The binding of Shiga-like toxin 1 (Stx1) and Shiga-like toxin 2 (Stx2) to a mucin-like fusion protein, P-selectin glycoprotein ligand-1/mouse IgG2b (PSGL-1/mIgG2b), carrying multiple copies of the blood group P1 determinant on O-glycans was investigated with western blot and the biosensor Biacore. 24082034 1 34 theme glycoprotein 238:249 arg1 IgG2b 266:270 P-selectin glycoprotein ligand-1/mouse IgG2b 227:270 P-selectin glycoprotein ligand-1/mouse IgG2b (PSGL-1/mIgG2b) 227:286 The binding of Shiga-like toxin 1 (Stx1) and Shiga-like toxin 2 (Stx2) to a mucin-like fusion protein, P-selectin glycoprotein ligand-1/mouse IgG2b (PSGL-1/mIgG2b), carrying multiple copies of the blood group P1 determinant on O-glycans was investigated with western blot and the biosensor Biacore. 24082034 1 34 theme glycoprotein 238:249 arg1 protein 218:224 a mucin-like fusion protein 198:224 a mucin-like fusion protein 198:224 The binding of Shiga-like toxin 1 (Stx1) and Shiga-like toxin 2 (Stx2) to a mucin-like fusion protein, P-selectin glycoprotein ligand-1/mouse IgG2b (PSGL-1/mIgG2b), carrying multiple copies of the blood group P1 determinant on O-glycans was investigated with western blot and the biosensor Biacore. 24082034 6 35 theme k 1149:1149 arg1 -albumin 1151:1158 P(k)-albumin 1147:1158 P(k)-albumin 1147:1158 Stx1 and Stx2 bound with high avidity to both PSGL-1/mIgG2b and P(k)-albumin, while the Stx1 binding was the strongest. 24082034 5 36 theme Biacore 928:934 arg1 assay 936:940 a Biacore assay 926:940 a Biacore assay 926:940 In a Biacore assay, Stx1 and Stx2 were immobilized on a dextran chip and the binding of purified PSGL-1/mIgG2b and a P(k)-albumin neoglycoprotein was analyzed. 24082034 1 37 theme Shiga-like 169:178 arg1 toxin 180:184 Shiga-like toxin 2 169:186 Shiga-like toxin 2 (Stx2) 169:193 The binding of Shiga-like toxin 1 (Stx1) and Shiga-like toxin 2 (Stx2) to a mucin-like fusion protein, P-selectin glycoprotein ligand-1/mouse IgG2b (PSGL-1/mIgG2b), carrying multiple copies of the blood group P1 determinant on O-glycans was investigated with western blot and the biosensor Biacore. 24082034 1 37 theme Shiga-like 169:178 arg1 Stx2 189:192 Stx2 189:192 Stx2 189:192 The binding of Shiga-like toxin 1 (Stx1) and Shiga-like toxin 2 (Stx2) to a mucin-like fusion protein, P-selectin glycoprotein ligand-1/mouse IgG2b (PSGL-1/mIgG2b), carrying multiple copies of the blood group P1 determinant on O-glycans was investigated with western blot and the biosensor Biacore. 24082034 1 38 theme ligand-1/mouse 251:264 arg1 PSGL-1/mIgG2b 273:285 PSGL-1/mIgG2b 273:285 PSGL-1/mIgG2b 273:285 The binding of Shiga-like toxin 1 (Stx1) and Shiga-like toxin 2 (Stx2) to a mucin-like fusion protein, P-selectin glycoprotein ligand-1/mouse IgG2b (PSGL-1/mIgG2b), carrying multiple copies of the blood group P1 determinant on O-glycans was investigated with western blot and the biosensor Biacore. 24082034 1 38 theme ligand-1/mouse 251:264 arg1 IgG2b 266:270 P-selectin glycoprotein ligand-1/mouse IgG2b 227:270 P-selectin glycoprotein ligand-1/mouse IgG2b (PSGL-1/mIgG2b) 227:286 The binding of Shiga-like toxin 1 (Stx1) and Shiga-like toxin 2 (Stx2) to a mucin-like fusion protein, P-selectin glycoprotein ligand-1/mouse IgG2b (PSGL-1/mIgG2b), carrying multiple copies of the blood group P1 determinant on O-glycans was investigated with western blot and the biosensor Biacore. 24082034 1 38 theme ligand-1/mouse 251:264 arg1 protein 218:224 a mucin-like fusion protein 198:224 a mucin-like fusion protein 198:224 The binding of Shiga-like toxin 1 (Stx1) and Shiga-like toxin 2 (Stx2) to a mucin-like fusion protein, P-selectin glycoprotein ligand-1/mouse IgG2b (PSGL-1/mIgG2b), carrying multiple copies of the blood group P1 determinant on O-glycans was investigated with western blot and the biosensor Biacore. 24082034 1 39 theme determinant 336:346 arg1 copies 307:312 multiple copies 298:312 multiple copies of the blood group P1 determinant 298:346 The binding of Shiga-like toxin 1 (Stx1) and Shiga-like toxin 2 (Stx2) to a mucin-like fusion protein, P-selectin glycoprotein ligand-1/mouse IgG2b (PSGL-1/mIgG2b), carrying multiple copies of the blood group P1 determinant on O-glycans was investigated with western blot and the biosensor Biacore. 24082034 5 40 theme -albumin 1044:1051 arg1 neoglycoprotein 1053:1067 a P(k)-albumin neoglycoprotein 1038:1067 a P(k)-albumin neoglycoprotein 1038:1067 In a Biacore assay, Stx1 and Stx2 were immobilized on a dextran chip and the binding of purified PSGL-1/mIgG2b and a P(k)-albumin neoglycoprotein was analyzed. 24082034 2 41 theme Chinese 423:429 arg1 cells 458:462 Chinese hamster ovary K-1 (CHO-K1) cells 423:462 Chinese hamster ovary K-1 (CHO-K1) cells 423:462 Chinese hamster ovary K-1 (CHO-K1) cells were stably transfected with linearized plasmids encoding the PSGL-1/mIgG2b fusion protein, the pigeon α1,4-galactosyltransferase (α4Gal-T) and the core 2 β1,6-N-acetylglucosaminyltransferase (C2GnT-I). 24082034 1 42 theme toxin 180:184 arg1 binding 128:134 The binding 124:134 The binding of Shiga-like toxin 1 (Stx1) and Shiga-like toxin 2 (Stx2) to a mucin-like fusion protein, P-selectin glycoprotein ligand-1/mouse IgG2b (PSGL-1/mIgG2b), carrying multiple copies of the blood group P1 determinant on O-glycans 124:359 The binding of Shiga-like toxin 1 (Stx1) and Shiga-like toxin 2 (Stx2) to a mucin-like fusion protein, P-selectin glycoprotein ligand-1/mouse IgG2b (PSGL-1/mIgG2b), carrying multiple copies of the blood group P1 determinant on O-glycans was investigated with western blot and the biosensor Biacore. 24082034 2 43 theme ovary 439:443 arg1 cells 458:462 Chinese hamster ovary K-1 (CHO-K1) cells 423:462 Chinese hamster ovary K-1 (CHO-K1) cells 423:462 Chinese hamster ovary K-1 (CHO-K1) cells were stably transfected with linearized plasmids encoding the PSGL-1/mIgG2b fusion protein, the pigeon α1,4-galactosyltransferase (α4Gal-T) and the core 2 β1,6-N-acetylglucosaminyltransferase (C2GnT-I). 24082034 8 44 theme high 1468:1471 arg1 avidity 1473:1479 high avidity 1468:1479 high avidity 1468:1479 P1-decorated PSGL-1/mIgG2b bound with high avidity to both Stx1 and Stx2, and as such constitutes a potential therapeutic inhibitor of these toxins. 24082034 2 45 theme linearized 493:502 arg1 plasmids 504:511 linearized plasmids 493:511 linearized plasmids encoding the PSGL-1/mIgG2b fusion protein, the pigeon α1,4-galactosyltransferase (α4Gal-T) and the core 2 β1,6-N-acetylglucosaminyltransferase (C2GnT-I) 493:664 Chinese hamster ovary K-1 (CHO-K1) cells were stably transfected with linearized plasmids encoding the PSGL-1/mIgG2b fusion protein, the pigeon α1,4-galactosyltransferase (α4Gal-T) and the core 2 β1,6-N-acetylglucosaminyltransferase (C2GnT-I). 24082034 5 46 theme dextran 979:985 arg1 chip 987:990 a dextran chip 977:990 a dextran chip 977:990 In a Biacore assay, Stx1 and Stx2 were immobilized on a dextran chip and the binding of purified PSGL-1/mIgG2b and a P(k)-albumin neoglycoprotein was analyzed. 24082034 2 47 theme K-1 445:447 arg1 cells 458:462 Chinese hamster ovary K-1 (CHO-K1) cells 423:462 Chinese hamster ovary K-1 (CHO-K1) cells 423:462 Chinese hamster ovary K-1 (CHO-K1) cells were stably transfected with linearized plasmids encoding the PSGL-1/mIgG2b fusion protein, the pigeon α1,4-galactosyltransferase (α4Gal-T) and the core 2 β1,6-N-acetylglucosaminyltransferase (C2GnT-I). 24082034 0 48 theme high 28:31 arg1 avidity 33:39 high avidity 28:39 high avidity 28:39 Shiga-like toxin binds with high avidity to multivalent O-linked blood group P1 determinants on mucin-type fusion proteins. 24082034 3 49 theme released 770:777 arg1 O-glycans 779:787 released O-glycans 770:787 released O-glycans 770:787 Western blot analyses of purified PSGL-1/mIgG2b and liquid chromatography-mass spectrometry (LC-MS) of released O-glycans confirmed the presence of the P1 determinant. 24082034 2 50 theme hamster 431:437 arg1 cells 458:462 Chinese hamster ovary K-1 (CHO-K1) cells 423:462 Chinese hamster ovary K-1 (CHO-K1) cells 423:462 Chinese hamster ovary K-1 (CHO-K1) cells were stably transfected with linearized plasmids encoding the PSGL-1/mIgG2b fusion protein, the pigeon α1,4-galactosyltransferase (α4Gal-T) and the core 2 β1,6-N-acetylglucosaminyltransferase (C2GnT-I). 24082034 5 51 theme P 1040:1040 arg1 neoglycoprotein 1053:1067 a P(k)-albumin neoglycoprotein 1038:1067 a P(k)-albumin neoglycoprotein 1038:1067 In a Biacore assay, Stx1 and Stx2 were immobilized on a dextran chip and the binding of purified PSGL-1/mIgG2b and a P(k)-albumin neoglycoprotein was analyzed. 24082034 7 52 theme P1 1357:1358 arg1 determinants 1360:1371 multiple, O-linked P1 determinants 1338:1371 multiple, O-linked P1 determinants on a simultaneously expressed mucin-type fusion protein 1338:1427 In summary, we have shown that the pigeon α4Gal-T can be aberrantly expressed in CHO cells together with the core 2 enzyme to generate multiple, O-linked P1 determinants on a simultaneously expressed mucin-type fusion protein. 24082034 1 53 gly glycoprotein 238:249 arg1 glycoprotein 238:249 P-selectin glycoprotein ligand-1/mouse IgG2b 227:270 P-selectin glycoprotein ligand-1/mouse IgG2b (PSGL-1/mIgG2b) 227:286 The binding of Shiga-like toxin 1 (Stx1) and Shiga-like toxin 2 (Stx2) to a mucin-like fusion protein, P-selectin glycoprotein ligand-1/mouse IgG2b (PSGL-1/mIgG2b), carrying multiple copies of the blood group P1 determinant on O-glycans was investigated with western blot and the biosensor Biacore. 24082034 7 54 theme expressed 1393:1401 arg1 protein 1421:1427 a simultaneously expressed mucin-type fusion protein 1376:1427 a simultaneously expressed mucin-type fusion protein 1376:1427 In summary, we have shown that the pigeon α4Gal-T can be aberrantly expressed in CHO cells together with the core 2 enzyme to generate multiple, O-linked P1 determinants on a simultaneously expressed mucin-type fusion protein. 24082034 0 55 theme multivalent 44:54 arg1 determinants 80:91 multivalent O-linked blood group P1 determinants 44:91 multivalent O-linked blood group P1 determinants on mucin-type fusion proteins 44:121 Shiga-like toxin binds with high avidity to multivalent O-linked blood group P1 determinants on mucin-type fusion proteins. 24082034 3 56 theme O-glycans 779:787 arg1 analyses 680:687 Western blot analyses 667:687 Western blot analyses of purified PSGL-1/mIgG2b 667:713 Western blot analyses of purified PSGL-1/mIgG2b and liquid chromatography-mass spectrometry (LC-MS) of released O-glycans confirmed the presence of the P1 determinant. 24082034 3 56 theme O-glycans 779:787 arg1 LC-MS 760:764 LC-MS 760:764 LC-MS 760:764 Western blot analyses of purified PSGL-1/mIgG2b and liquid chromatography-mass spectrometry (LC-MS) of released O-glycans confirmed the presence of the P1 determinant. 24082034 3 56 theme O-glycans 779:787 arg1 spectrometry 746:757 liquid chromatography-mass spectrometry 719:757 liquid chromatography-mass spectrometry (LC-MS) of released O-glycans 719:787 Western blot analyses of purified PSGL-1/mIgG2b and liquid chromatography-mass spectrometry (LC-MS) of released O-glycans confirmed the presence of the P1 determinant. 24082034 2 57 theme CHO-K1 450:455 arg1 cells 458:462 Chinese hamster ovary K-1 (CHO-K1) cells 423:462 Chinese hamster ovary K-1 (CHO-K1) cells 423:462 Chinese hamster ovary K-1 (CHO-K1) cells were stably transfected with linearized plasmids encoding the PSGL-1/mIgG2b fusion protein, the pigeon α1,4-galactosyltransferase (α4Gal-T) and the core 2 β1,6-N-acetylglucosaminyltransferase (C2GnT-I). 24082034 3 58 theme purified 692:699 arg1 PSGL-1/mIgG2b 701:713 purified PSGL-1/mIgG2b 692:713 purified PSGL-1/mIgG2b 692:713 Western blot analyses of purified PSGL-1/mIgG2b and liquid chromatography-mass spectrometry (LC-MS) of released O-glycans confirmed the presence of the P1 determinant. 24082034 2 59 theme fusion 540:545 arg1 protein 547:553 the PSGL-1/mIgG2b fusion protein 522:553 the PSGL-1/mIgG2b fusion protein 522:553 Chinese hamster ovary K-1 (CHO-K1) cells were stably transfected with linearized plasmids encoding the PSGL-1/mIgG2b fusion protein, the pigeon α1,4-galactosyltransferase (α4Gal-T) and the core 2 β1,6-N-acetylglucosaminyltransferase (C2GnT-I). 24082034 7 60 theme mucin-type 1403:1412 arg1 protein 1421:1427 a simultaneously expressed mucin-type fusion protein 1376:1427 a simultaneously expressed mucin-type fusion protein 1376:1427 In summary, we have shown that the pigeon α4Gal-T can be aberrantly expressed in CHO cells together with the core 2 enzyme to generate multiple, O-linked P1 determinants on a simultaneously expressed mucin-type fusion protein. 24082034 4 61 theme Western 835:841 arg1 analysis 848:855 Western blot analysis 835:855 Western blot analysis 835:855 Western blot analysis indicated strong binding of Stx1, but not Stx2, to PSGL-1/mIgG2b. 24082034 2 62 theme PSGL-1/mIgG2b 526:538 arg1 protein 547:553 the PSGL-1/mIgG2b fusion protein 522:553 the PSGL-1/mIgG2b fusion protein 522:553 Chinese hamster ovary K-1 (CHO-K1) cells were stably transfected with linearized plasmids encoding the PSGL-1/mIgG2b fusion protein, the pigeon α1,4-galactosyltransferase (α4Gal-T) and the core 2 β1,6-N-acetylglucosaminyltransferase (C2GnT-I). 24082034 7 63 theme fusion 1414:1419 arg1 protein 1421:1427 a simultaneously expressed mucin-type fusion protein 1376:1427 a simultaneously expressed mucin-type fusion protein 1376:1427 In summary, we have shown that the pigeon α4Gal-T can be aberrantly expressed in CHO cells together with the core 2 enzyme to generate multiple, O-linked P1 determinants on a simultaneously expressed mucin-type fusion protein. 24082034 7 64 from determinants 1360:1371 arg1 protein 1421:1427 a simultaneously expressed mucin-type fusion protein 1376:1427 a simultaneously expressed mucin-type fusion protein 1376:1427 In summary, we have shown that the pigeon α4Gal-T can be aberrantly expressed in CHO cells together with the core 2 enzyme to generate multiple, O-linked P1 determinants on a simultaneously expressed mucin-type fusion protein. 24082034 0 65 link O-linked 56:63 arg1 determinants 80:91 multivalent O-linked blood group P1 determinants 44:91 multivalent O-linked blood group P1 determinants on mucin-type fusion proteins 44:121 Shiga-like toxin binds with high avidity to multivalent O-linked blood group P1 determinants on mucin-type fusion proteins. 24082034 3 66 theme chromatography-mass 726:744 arg1 LC-MS 760:764 LC-MS 760:764 LC-MS 760:764 Western blot analyses of purified PSGL-1/mIgG2b and liquid chromatography-mass spectrometry (LC-MS) of released O-glycans confirmed the presence of the P1 determinant. 24082034 3 66 theme chromatography-mass 726:744 arg1 spectrometry 746:757 liquid chromatography-mass spectrometry 719:757 liquid chromatography-mass spectrometry (LC-MS) of released O-glycans 719:787 Western blot analyses of purified PSGL-1/mIgG2b and liquid chromatography-mass spectrometry (LC-MS) of released O-glycans confirmed the presence of the P1 determinant. 24082034 1 67 theme western 383:389 arg1 blot 391:394 western blot 383:394 western blot 383:394 The binding of Shiga-like toxin 1 (Stx1) and Shiga-like toxin 2 (Stx2) to a mucin-like fusion protein, P-selectin glycoprotein ligand-1/mouse IgG2b (PSGL-1/mIgG2b), carrying multiple copies of the blood group P1 determinant on O-glycans was investigated with western blot and the biosensor Biacore. 24082034 6 68 theme P 1147:1147 arg1 -albumin 1151:1158 P(k)-albumin 1147:1158 P(k)-albumin 1147:1158 Stx1 and Stx2 bound with high avidity to both PSGL-1/mIgG2b and P(k)-albumin, while the Stx1 binding was the strongest. 24082034 1 69 contain carrying 289:296 arg1 IgG2b 266:270 P-selectin glycoprotein ligand-1/mouse IgG2b 227:270 P-selectin glycoprotein ligand-1/mouse IgG2b (PSGL-1/mIgG2b) 227:286 The binding of Shiga-like toxin 1 (Stx1) and Shiga-like toxin 2 (Stx2) to a mucin-like fusion protein, P-selectin glycoprotein ligand-1/mouse IgG2b (PSGL-1/mIgG2b), carrying multiple copies of the blood group P1 determinant on O-glycans was investigated with western blot and the biosensor Biacore. 24082034 1 69 contain carrying 289:296 arg1 protein 218:224 a mucin-like fusion protein 198:224 a mucin-like fusion protein 198:224 The binding of Shiga-like toxin 1 (Stx1) and Shiga-like toxin 2 (Stx2) to a mucin-like fusion protein, P-selectin glycoprotein ligand-1/mouse IgG2b (PSGL-1/mIgG2b), carrying multiple copies of the blood group P1 determinant on O-glycans was investigated with western blot and the biosensor Biacore. 24082034 1 69 contain carrying 289:296 arg2 copies 307:312 multiple copies 298:312 multiple copies of the blood group P1 determinant 298:346 The binding of Shiga-like toxin 1 (Stx1) and Shiga-like toxin 2 (Stx2) to a mucin-like fusion protein, P-selectin glycoprotein ligand-1/mouse IgG2b (PSGL-1/mIgG2b), carrying multiple copies of the blood group P1 determinant on O-glycans was investigated with western blot and the biosensor Biacore. 24082034 5 70 theme purified 1011:1018 arg1 PSGL-1/mIgG2b 1020:1032 purified PSGL-1/mIgG2b 1011:1032 purified PSGL-1/mIgG2b 1011:1032 In a Biacore assay, Stx1 and Stx2 were immobilized on a dextran chip and the binding of purified PSGL-1/mIgG2b and a P(k)-albumin neoglycoprotein was analyzed. 24082034 0 71 theme blood 65:69 arg1 determinants 80:91 multivalent O-linked blood group P1 determinants 44:91 multivalent O-linked blood group P1 determinants on mucin-type fusion proteins 44:121 Shiga-like toxin binds with high avidity to multivalent O-linked blood group P1 determinants on mucin-type fusion proteins. 24082034 0 72 from determinants 80:91 arg1 proteins 114:121 mucin-type fusion proteins 96:121 mucin-type fusion proteins 96:121 Shiga-like toxin binds with high avidity to multivalent O-linked blood group P1 determinants on mucin-type fusion proteins. 24082034 7 73 theme pigeon 1238:1243 arg1 α4Gal-T 1245:1251 the pigeon α4Gal-T 1234:1251 the pigeon α4Gal-T 1234:1251 In summary, we have shown that the pigeon α4Gal-T can be aberrantly expressed in CHO cells together with the core 2 enzyme to generate multiple, O-linked P1 determinants on a simultaneously expressed mucin-type fusion protein. 24082034 8 74 theme P1-decorated 1430:1441 arg1 PSGL-1/mIgG2b 1443:1455 P1-decorated PSGL-1/mIgG2b 1430:1455 P1-decorated PSGL-1/mIgG2b bound with high avidity to both Stx1 and Stx2, and as such 1430:1514 P1-decorated PSGL-1/mIgG2b bound with high avidity to both Stx1 and Stx2, and as such constitutes a potential therapeutic inhibitor of these toxins. 24082034 4 75 theme Stx2 899:902 arg1 binding 874:880 strong binding 867:880 strong binding of Stx1, but not Stx2, to PSGL-1/mIgG2b 867:920 Western blot analysis indicated strong binding of Stx1, but not Stx2, to PSGL-1/mIgG2b. 24082034 0 76 theme O-linked 56:63 arg1 determinants 80:91 multivalent O-linked blood group P1 determinants 44:91 multivalent O-linked blood group P1 determinants on mucin-type fusion proteins 44:121 Shiga-like toxin binds with high avidity to multivalent O-linked blood group P1 determinants on mucin-type fusion proteins. 24082034 8 77 dep potential 1530:1538 arg1 therapeutic 1540:1550 therapeutic 1540:1550 therapeutic 1540:1550 P1-decorated PSGL-1/mIgG2b bound with high avidity to both Stx1 and Stx2, and as such constitutes a potential therapeutic inhibitor of these toxins. 24082034 1 78 theme Shiga-like 139:148 arg1 toxin 150:154 Shiga-like toxin 1 139:156 Shiga-like toxin 1 (Stx1) 139:163 The binding of Shiga-like toxin 1 (Stx1) and Shiga-like toxin 2 (Stx2) to a mucin-like fusion protein, P-selectin glycoprotein ligand-1/mouse IgG2b (PSGL-1/mIgG2b), carrying multiple copies of the blood group P1 determinant on O-glycans was investigated with western blot and the biosensor Biacore. 24082034 1 78 theme Shiga-like 139:148 arg1 Stx1 159:162 Stx1 159:162 Stx1 159:162 The binding of Shiga-like toxin 1 (Stx1) and Shiga-like toxin 2 (Stx2) to a mucin-like fusion protein, P-selectin glycoprotein ligand-1/mouse IgG2b (PSGL-1/mIgG2b), carrying multiple copies of the blood group P1 determinant on O-glycans was investigated with western blot and the biosensor Biacore. 24082034 7 79 theme CHO 1284:1286 arg1 cells 1288:1292 CHO cells 1284:1292 CHO cells together with the core 2 enzyme 1284:1324 In summary, we have shown that the pigeon α4Gal-T can be aberrantly expressed in CHO cells together with the core 2 enzyme to generate multiple, O-linked P1 determinants on a simultaneously expressed mucin-type fusion protein. 28166708 9 0 dep FRAP 1081:1084 arg1 568.3 μg/mL 1102:1112 568.3 μg/mL 1102:1112 568.3 μg/mL 1102:1112 RESULTS Antioxidant activities in the DPPH (IC50 43.5 and 66.2 μg/mL), FRAP (IC50 312.6 and 568.3 μg/mL) and NO radical scavenging assays (IC50 285.0 and 972.6 μg/mL) were observed in the leaf and bark ethanol extracts, respectively. 28166708 9 0 dep FRAP 1081:1084 arg1 IC50 1087:1090 IC50 312.6 1087:1096 IC50 312.6 1087:1096 RESULTS Antioxidant activities in the DPPH (IC50 43.5 and 66.2 μg/mL), FRAP (IC50 312.6 and 568.3 μg/mL) and NO radical scavenging assays (IC50 285.0 and 972.6 μg/mL) were observed in the leaf and bark ethanol extracts, respectively. 28166708 5 1 theme factor-alpha 634:645 arg1 release 585:591 the release 581:591 the release of nitric oxide (NO) and tumour necrosis factor-alpha (TNF-α) 581:653 MATERIALS AND METHODS The anti-inflammatory activity of ethanol extracts of the leaf and bark of S. australis (1-100 μg/mL) were studied in lipopolysaccharide/interferon γ stimulated murine macrophages RAW 264.7 cells (24 h incubation) by investigating the release of nitric oxide (NO) and tumour necrosis factor-alpha (TNF-α) and in the TNF-α-induced nuclear factor kappa (NF-κB) assay. 28166708 10 2 theme 100 μg/mL 1370:1378 arg1 concentrations 1346:1359 concentrations 1346:1359 concentrations of 2 and 100 μg/mL, respectively 1346:1392 Solely the leaf extract showed significant inhibition of NO and TNF-α production in RAW264.7 cells at concentrations of 2 and 100 μg/mL, respectively, and suppression of TNF-α inhibition of NF-κB by 12.8 and 20.4% at concentrations of 50 and 100 μg/mL, respectively. 28166708 4 3 dep in 243:244 arg1 vitro 246:250 vitro 246:250 vitro 246:250 OBJECTIVE To evaluate the in vitro anti-inflammatory, antioxidant and antimicrobial properties of S. australis. 28166708 5 4 theme lipopolysaccharide/interferon 468:496 arg1 γ 498:498 lipopolysaccharide/interferon γ 468:498 lipopolysaccharide/interferon γ 468:498 MATERIALS AND METHODS The anti-inflammatory activity of ethanol extracts of the leaf and bark of S. australis (1-100 μg/mL) were studied in lipopolysaccharide/interferon γ stimulated murine macrophages RAW 264.7 cells (24 h incubation) by investigating the release of nitric oxide (NO) and tumour necrosis factor-alpha (TNF-α) and in the TNF-α-induced nuclear factor kappa (NF-κB) assay. 28166708 5 5 theme anti-inflammatory 355:370 arg1 activity 372:379 The anti-inflammatory activity 351:379 The anti-inflammatory activity of ethanol extracts of the leaf 351:411 MATERIALS AND METHODS The anti-inflammatory activity of ethanol extracts of the leaf and bark of S. australis (1-100 μg/mL) were studied in lipopolysaccharide/interferon γ stimulated murine macrophages RAW 264.7 cells (24 h incubation) by investigating the release of nitric oxide (NO) and tumour necrosis factor-alpha (TNF-α) and in the TNF-α-induced nuclear factor kappa (NF-κB) assay. 28166708 9 6 dep DPPH 1048:1051 arg1 66.2 μg/mL 1068:1077 66.2 μg/mL 1068:1077 66.2 μg/mL 1068:1077 RESULTS Antioxidant activities in the DPPH (IC50 43.5 and 66.2 μg/mL), FRAP (IC50 312.6 and 568.3 μg/mL) and NO radical scavenging assays (IC50 285.0 and 972.6 μg/mL) were observed in the leaf and bark ethanol extracts, respectively. 28166708 9 6 dep DPPH 1048:1051 arg1 IC50 1054:1057 IC50 43.5 1054:1062 IC50 43.5 1054:1062 RESULTS Antioxidant activities in the DPPH (IC50 43.5 and 66.2 μg/mL), FRAP (IC50 312.6 and 568.3 μg/mL) and NO radical scavenging assays (IC50 285.0 and 972.6 μg/mL) were observed in the leaf and bark ethanol extracts, respectively. 28166708 8 7 theme Chemical 963:970 arg1 composition 972:982 Chemical composition 963:982 Chemical composition 963:982 Chemical composition was assessed by LC-MS/MS. 28166708 5 8 theme NF-κB 702:706 arg1 assay 709:713 the TNF-α-induced nuclear factor kappa (NF-κB) assay 662:713 the TNF-α-induced nuclear factor kappa (NF-κB) assay 662:713 MATERIALS AND METHODS The anti-inflammatory activity of ethanol extracts of the leaf and bark of S. australis (1-100 μg/mL) were studied in lipopolysaccharide/interferon γ stimulated murine macrophages RAW 264.7 cells (24 h incubation) by investigating the release of nitric oxide (NO) and tumour necrosis factor-alpha (TNF-α) and in the TNF-α-induced nuclear factor kappa (NF-κB) assay. 28166708 10 9 from suppression 1399:1409 arg1 concentrations 1346:1359 concentrations 1346:1359 concentrations of 2 and 100 μg/mL, respectively 1346:1392 Solely the leaf extract showed significant inhibition of NO and TNF-α production in RAW264.7 cells at concentrations of 2 and 100 μg/mL, respectively, and suppression of TNF-α inhibition of NF-κB by 12.8 and 20.4% at concentrations of 50 and 100 μg/mL, respectively. 28166708 10 9 from suppression 1399:1409 arg1 cells 1337:1341 RAW264.7 cells 1328:1341 RAW264.7 cells 1328:1341 Solely the leaf extract showed significant inhibition of NO and TNF-α production in RAW264.7 cells at concentrations of 2 and 100 μg/mL, respectively, and suppression of TNF-α inhibition of NF-κB by 12.8 and 20.4% at concentrations of 50 and 100 μg/mL, respectively. 28166708 5 10 theme nuclear 680:686 arg1 factor 688:693 the TNF-α-induced nuclear factor 662:693 the TNF-α-induced nuclear factor kappa (NF-κB) assay 662:713 MATERIALS AND METHODS The anti-inflammatory activity of ethanol extracts of the leaf and bark of S. australis (1-100 μg/mL) were studied in lipopolysaccharide/interferon γ stimulated murine macrophages RAW 264.7 cells (24 h incubation) by investigating the release of nitric oxide (NO) and tumour necrosis factor-alpha (TNF-α) and in the TNF-α-induced nuclear factor kappa (NF-κB) assay. 28166708 4 11 theme in 243:244 arg1 properties 301:310 the in vitro anti-inflammatory, antioxidant and antimicrobial properties 239:310 the in vitro anti-inflammatory, antioxidant and antimicrobial properties of S. australis 239:326 OBJECTIVE To evaluate the in vitro anti-inflammatory, antioxidant and antimicrobial properties of S. australis. 28166708 9 12 theme Antioxidant 1018:1028 arg1 activities 1030:1039 Antioxidant activities 1018:1039 Antioxidant activities in the DPPH (IC50 43.5 and 66.2 μg/mL), FRAP (IC50 312.6 and 568.3 μg/mL) 1018:1113 RESULTS Antioxidant activities in the DPPH (IC50 43.5 and 66.2 μg/mL), FRAP (IC50 312.6 and 568.3 μg/mL) and NO radical scavenging assays (IC50 285.0 and 972.6 μg/mL) were observed in the leaf and bark ethanol extracts, respectively. 28166708 5 13 theme kappa 695:699 arg1 assay 709:713 the TNF-α-induced nuclear factor kappa (NF-κB) assay 662:713 the TNF-α-induced nuclear factor kappa (NF-κB) assay 662:713 MATERIALS AND METHODS The anti-inflammatory activity of ethanol extracts of the leaf and bark of S. australis (1-100 μg/mL) were studied in lipopolysaccharide/interferon γ stimulated murine macrophages RAW 264.7 cells (24 h incubation) by investigating the release of nitric oxide (NO) and tumour necrosis factor-alpha (TNF-α) and in the TNF-α-induced nuclear factor kappa (NF-κB) assay. 28166708 9 14 theme ethanol 1212:1218 arg1 extracts 1220:1227 the leaf and bark ethanol extracts 1194:1227 extracts 1220:1227 RESULTS Antioxidant activities in the DPPH (IC50 43.5 and 66.2 μg/mL), FRAP (IC50 312.6 and 568.3 μg/mL) and NO radical scavenging assays (IC50 285.0 and 972.6 μg/mL) were observed in the leaf and bark ethanol extracts, respectively. 28166708 9 15 dep assays 1141:1146 arg1 IC50 1149:1152 IC50 285.0 1149:1158 IC50 285.0 1149:1158 RESULTS Antioxidant activities in the DPPH (IC50 43.5 and 66.2 μg/mL), FRAP (IC50 312.6 and 568.3 μg/mL) and NO radical scavenging assays (IC50 285.0 and 972.6 μg/mL) were observed in the leaf and bark ethanol extracts, respectively. 28166708 9 15 dep assays 1141:1146 arg1 972.6 μg/mL 1164:1174 972.6 μg/mL 1164:1174 972.6 μg/mL 1164:1174 RESULTS Antioxidant activities in the DPPH (IC50 43.5 and 66.2 μg/mL), FRAP (IC50 312.6 and 568.3 μg/mL) and NO radical scavenging assays (IC50 285.0 and 972.6 μg/mL) were observed in the leaf and bark ethanol extracts, respectively. 28166708 9 15 dep assays 1141:1146 arg1 assays 1141:1146 NO radical scavenging assays 1119:1146 NO radical scavenging assays (IC50 285.0 and 972.6 μg/mL) 1119:1175 RESULTS Antioxidant activities in the DPPH (IC50 43.5 and 66.2 μg/mL), FRAP (IC50 312.6 and 568.3 μg/mL) and NO radical scavenging assays (IC50 285.0 and 972.6 μg/mL) were observed in the leaf and bark ethanol extracts, respectively. 28166708 1 16 dep Cham 120:123 arg1 australis 110:118 CONTEXT Sambucus australis 93:118 CONTEXT Sambucus australis 93:118 CONTEXT Sambucus australis Cham. 28166708 0 17 theme Sambucus 73:80 arg1 australis 82:90 Sambucus australis 73:90 Sambucus australis 73:90 Potential anti-inflammatory, antioxidant and antimicrobial activities of Sambucus australis. 28166708 11 18 theme antibacterial 1538:1550 arg1 activity 1552:1559 antibacterial activity 1538:1559 antibacterial activity against Salmonella typhimurium (MIC 250 μg/mL) and Klebsiella pneumoniae (MIC 250 μg/mL) 1538:1648 The extract also exhibited antibacterial activity against Salmonella typhimurium (MIC 250 μg/mL) and Klebsiella pneumoniae (MIC 250 μg/mL). 28166708 13 19 theme prominent 1833:1841 arg1 effects 1860:1866 prominent anti-inflammatory effects 1833:1866 prominent anti-inflammatory effects 1833:1866 DISCUSSION AND CONCLUSION The results indicate that the ethanol leaf extract of S. australis exhibit prominent anti-inflammatory effects. 28166708 7 20 theme scavenging 944:953 arg1 assays 955:960 the NO scavenging assays 937:960 the NO scavenging assays 937:960 Antioxidant activity was determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP) and the NO scavenging assays. 28166708 5 21 theme extracts 392:399 arg1 bark 417:420 bark 417:420 bark of S. australis (1-100 μg/mL) 417:450 MATERIALS AND METHODS The anti-inflammatory activity of ethanol extracts of the leaf and bark of S. australis (1-100 μg/mL) were studied in lipopolysaccharide/interferon γ stimulated murine macrophages RAW 264.7 cells (24 h incubation) by investigating the release of nitric oxide (NO) and tumour necrosis factor-alpha (TNF-α) and in the TNF-α-induced nuclear factor kappa (NF-κB) assay. 28166708 5 21 theme extracts 392:399 arg1 activity 372:379 The anti-inflammatory activity 351:379 The anti-inflammatory activity of ethanol extracts of the leaf 351:411 MATERIALS AND METHODS The anti-inflammatory activity of ethanol extracts of the leaf and bark of S. australis (1-100 μg/mL) were studied in lipopolysaccharide/interferon γ stimulated murine macrophages RAW 264.7 cells (24 h incubation) by investigating the release of nitric oxide (NO) and tumour necrosis factor-alpha (TNF-α) and in the TNF-α-induced nuclear factor kappa (NF-κB) assay. 28166708 9 22 dep RESULTS 1010:1016 arg1 activities 1030:1039 Antioxidant activities 1018:1039 Antioxidant activities in the DPPH (IC50 43.5 and 66.2 μg/mL), FRAP (IC50 312.6 and 568.3 μg/mL) 1018:1113 RESULTS Antioxidant activities in the DPPH (IC50 43.5 and 66.2 μg/mL), FRAP (IC50 312.6 and 568.3 μg/mL) and NO radical scavenging assays (IC50 285.0 and 972.6 μg/mL) were observed in the leaf and bark ethanol extracts, respectively. 28166708 13 23 theme ethanol 1788:1794 arg1 extract 1801:1807 the ethanol leaf extract 1784:1807 the ethanol leaf extract of S. australis 1784:1823 DISCUSSION AND CONCLUSION The results indicate that the ethanol leaf extract of S. australis exhibit prominent anti-inflammatory effects. 28166708 10 24 theme inhibition 1420:1429 arg1 inhibition 1287:1296 significant inhibition 1275:1296 significant inhibition of NO and TNF-α production in RAW264.7 cells at concentrations of 2 and 100 μg/mL, respectively 1275:1392 Solely the leaf extract showed significant inhibition of NO and TNF-α production in RAW264.7 cells at concentrations of 2 and 100 μg/mL, respectively, and suppression of TNF-α inhibition of NF-κB by 12.8 and 20.4% at concentrations of 50 and 100 μg/mL, respectively. 28166708 10 24 theme inhibition 1420:1429 arg1 suppression 1399:1409 suppression 1399:1409 suppression of TNF-α inhibition of NF-κB by 12.8 and 20.4% at concentrations of 50 and 100 μg/mL, respectively 1399:1508 Solely the leaf extract showed significant inhibition of NO and TNF-α production in RAW264.7 cells at concentrations of 2 and 100 μg/mL, respectively, and suppression of TNF-α inhibition of NF-κB by 12.8 and 20.4% at concentrations of 50 and 100 μg/mL, respectively. 28166708 3 25 theme Brazilian 160:168 arg1 medicine 175:182 Brazilian folk medicine 160:182 Brazilian folk medicine 160:182 (Adoxaceae) is used in Brazilian folk medicine to treat inflammatory disorders. 28166708 4 26 theme anti-inflammatory 252:268 arg1 properties 301:310 the in vitro anti-inflammatory, antioxidant and antimicrobial properties 239:310 the in vitro anti-inflammatory, antioxidant and antimicrobial properties of S. australis 239:326 OBJECTIVE To evaluate the in vitro anti-inflammatory, antioxidant and antimicrobial properties of S. australis. 28166708 1 27 theme CONTEXT 93:99 arg1 australis 110:118 CONTEXT Sambucus australis 93:118 CONTEXT Sambucus australis 93:118 CONTEXT Sambucus australis Cham. 28166708 4 28 theme australis 318:326 arg1 properties 301:310 the in vitro anti-inflammatory, antioxidant and antimicrobial properties 239:310 the in vitro anti-inflammatory, antioxidant and antimicrobial properties of S. australis 239:326 OBJECTIVE To evaluate the in vitro anti-inflammatory, antioxidant and antimicrobial properties of S. australis. 28166708 9 29 from activities 1030:1039 arg1 DPPH 1048:1051 the DPPH 1044:1051 the DPPH (IC50 43.5 and 66.2 μg/mL) 1044:1078 RESULTS Antioxidant activities in the DPPH (IC50 43.5 and 66.2 μg/mL), FRAP (IC50 312.6 and 568.3 μg/mL) and NO radical scavenging assays (IC50 285.0 and 972.6 μg/mL) were observed in the leaf and bark ethanol extracts, respectively. 28166708 9 29 from activities 1030:1039 arg1 FRAP 1081:1084 FRAP 1081:1084 FRAP (IC50 312.6 and 568.3 μg/mL) 1081:1113 RESULTS Antioxidant activities in the DPPH (IC50 43.5 and 66.2 μg/mL), FRAP (IC50 312.6 and 568.3 μg/mL) and NO radical scavenging assays (IC50 285.0 and 972.6 μg/mL) were observed in the leaf and bark ethanol extracts, respectively. 28166708 13 30 theme australis 1815:1823 arg1 extract 1801:1807 the ethanol leaf extract 1784:1807 the ethanol leaf extract of S. australis 1784:1823 DISCUSSION AND CONCLUSION The results indicate that the ethanol leaf extract of S. australis exhibit prominent anti-inflammatory effects. 28166708 0 31 theme Potential 0:8 arg1 activities 59:68 Potential anti-inflammatory, antioxidant and antimicrobial activities 0:68 Potential anti-inflammatory, antioxidant and antimicrobial activities of Sambucus australis 0:90 Potential anti-inflammatory, antioxidant and antimicrobial activities of Sambucus australis. 28166708 5 32 theme oxide 603:607 arg1 release 585:591 the release 581:591 the release of nitric oxide (NO) and tumour necrosis factor-alpha (TNF-α) 581:653 MATERIALS AND METHODS The anti-inflammatory activity of ethanol extracts of the leaf and bark of S. australis (1-100 μg/mL) were studied in lipopolysaccharide/interferon γ stimulated murine macrophages RAW 264.7 cells (24 h incubation) by investigating the release of nitric oxide (NO) and tumour necrosis factor-alpha (TNF-α) and in the TNF-α-induced nuclear factor kappa (NF-κB) assay. 28166708 4 33 theme antioxidant 271:281 arg1 properties 301:310 the in vitro anti-inflammatory, antioxidant and antimicrobial properties 239:310 the in vitro anti-inflammatory, antioxidant and antimicrobial properties of S. australis 239:326 OBJECTIVE To evaluate the in vitro anti-inflammatory, antioxidant and antimicrobial properties of S. australis. 28166708 13 34 theme leaf 1796:1799 arg1 extract 1801:1807 the ethanol leaf extract 1784:1807 the ethanol leaf extract of S. australis 1784:1823 DISCUSSION AND CONCLUSION The results indicate that the ethanol leaf extract of S. australis exhibit prominent anti-inflammatory effects. 28166708 4 35 theme antimicrobial 287:299 arg1 properties 301:310 the in vitro anti-inflammatory, antioxidant and antimicrobial properties 239:310 the in vitro anti-inflammatory, antioxidant and antimicrobial properties of S. australis 239:326 OBJECTIVE To evaluate the in vitro anti-inflammatory, antioxidant and antimicrobial properties of S. australis. 28166708 10 36 theme NF-κB 1434:1438 arg1 inhibition 1420:1429 TNF-α inhibition 1414:1429 TNF-α inhibition of NF-κB by 12.8 and 20.4% at concentrations of 50 and 100 μg/mL, respectively 1414:1508 Solely the leaf extract showed significant inhibition of NO and TNF-α production in RAW264.7 cells at concentrations of 2 and 100 μg/mL, respectively, and suppression of TNF-α inhibition of NF-κB by 12.8 and 20.4% at concentrations of 50 and 100 μg/mL, respectively. 28166708 3 37 dep used 152:155 arg1 Adoxaceae 138:146 Adoxaceae 138:146 Adoxaceae 138:146 (Adoxaceae) is used in Brazilian folk medicine to treat inflammatory disorders. 28166708 10 38 from production 1314:1323 arg1 cells 1337:1341 RAW264.7 cells 1328:1341 RAW264.7 cells 1328:1341 Solely the leaf extract showed significant inhibition of NO and TNF-α production in RAW264.7 cells at concentrations of 2 and 100 μg/mL, respectively, and suppression of TNF-α inhibition of NF-κB by 12.8 and 20.4% at concentrations of 50 and 100 μg/mL, respectively. 28166708 11 39 theme MIC 1635:1637 arg1 250 μg/mL 1639:1647 MIC 250 μg/mL 1635:1647 MIC 250 μg/mL 1635:1647 The extract also exhibited antibacterial activity against Salmonella typhimurium (MIC 250 μg/mL) and Klebsiella pneumoniae (MIC 250 μg/mL). 28166708 11 39 theme MIC 1635:1637 arg1 typhimurium 1580:1590 Salmonella typhimurium 1569:1590 Salmonella typhimurium (MIC 250 μg/mL) 1569:1606 The extract also exhibited antibacterial activity against Salmonella typhimurium (MIC 250 μg/mL) and Klebsiella pneumoniae (MIC 250 μg/mL). 28166708 11 40 dep Klebsiella 1612:1621 arg1 pneumoniae 1623:1632 Klebsiella pneumoniae 1612:1632 Klebsiella pneumoniae 1612:1632 The extract also exhibited antibacterial activity against Salmonella typhimurium (MIC 250 μg/mL) and Klebsiella pneumoniae (MIC 250 μg/mL). 28166708 6 41 theme microdilution 777:789 arg1 test 791:794 the microdilution test 773:794 the microdilution test (24 h incubation) 773:812 Minimum inhibitory concentration (MIC) was determined by the microdilution test (24 h incubation). 28166708 6 41 theme microdilution 777:789 arg1 incubation 802:811 24 h incubation 797:811 24 h incubation 797:811 Minimum inhibitory concentration (MIC) was determined by the microdilution test (24 h incubation). 28166708 10 42 theme significant 1275:1285 arg1 inhibition 1287:1296 significant inhibition 1275:1296 significant inhibition of NO and TNF-α production in RAW264.7 cells at concentrations of 2 and 100 μg/mL, respectively 1275:1392 Solely the leaf extract showed significant inhibition of NO and TNF-α production in RAW264.7 cells at concentrations of 2 and 100 μg/mL, respectively, and suppression of TNF-α inhibition of NF-κB by 12.8 and 20.4% at concentrations of 50 and 100 μg/mL, respectively. 28166708 9 43 theme radical 1122:1128 arg1 scavenging 1130:1139 NO radical scavenging 1119:1139 NO radical scavenging assays (IC50 285.0 and 972.6 μg/mL) 1119:1175 RESULTS Antioxidant activities in the DPPH (IC50 43.5 and 66.2 μg/mL), FRAP (IC50 312.6 and 568.3 μg/mL) and NO radical scavenging assays (IC50 285.0 and 972.6 μg/mL) were observed in the leaf and bark ethanol extracts, respectively. 28166708 10 44 theme production 1314:1323 arg1 inhibition 1287:1296 significant inhibition 1275:1296 significant inhibition of NO and TNF-α production in RAW264.7 cells at concentrations of 2 and 100 μg/mL, respectively 1275:1392 Solely the leaf extract showed significant inhibition of NO and TNF-α production in RAW264.7 cells at concentrations of 2 and 100 μg/mL, respectively, and suppression of TNF-α inhibition of NF-κB by 12.8 and 20.4% at concentrations of 50 and 100 μg/mL, respectively. 28166708 10 44 theme production 1314:1323 arg1 suppression 1399:1409 suppression 1399:1409 suppression of TNF-α inhibition of NF-κB by 12.8 and 20.4% at concentrations of 50 and 100 μg/mL, respectively 1399:1508 Solely the leaf extract showed significant inhibition of NO and TNF-α production in RAW264.7 cells at concentrations of 2 and 100 μg/mL, respectively, and suppression of TNF-α inhibition of NF-κB by 12.8 and 20.4% at concentrations of 50 and 100 μg/mL, respectively. 28166708 7 45 theme reducing 899:906 arg1 FRAP 927:930 FRAP 927:930 FRAP 927:930 Antioxidant activity was determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP) and the NO scavenging assays. 28166708 7 45 theme reducing 899:906 arg1 power 920:924 ferric reducing antioxidant power 892:924 ferric reducing antioxidant power (FRAP) 892:931 Antioxidant activity was determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP) and the NO scavenging assays. 28166708 6 46 theme Minimum 716:722 arg1 MIC 750:752 MIC 750:752 MIC 750:752 Minimum inhibitory concentration (MIC) was determined by the microdilution test (24 h incubation). 28166708 6 46 theme Minimum 716:722 arg1 concentration 735:747 Minimum inhibitory concentration 716:747 Minimum inhibitory concentration (MIC) 716:753 Minimum inhibitory concentration (MIC) was determined by the microdilution test (24 h incubation). 28166708 9 47 theme scavenging 1130:1139 arg1 IC50 1149:1152 IC50 285.0 1149:1158 IC50 285.0 1149:1158 RESULTS Antioxidant activities in the DPPH (IC50 43.5 and 66.2 μg/mL), FRAP (IC50 312.6 and 568.3 μg/mL) and NO radical scavenging assays (IC50 285.0 and 972.6 μg/mL) were observed in the leaf and bark ethanol extracts, respectively. 28166708 9 47 theme scavenging 1130:1139 arg1 972.6 μg/mL 1164:1174 972.6 μg/mL 1164:1174 972.6 μg/mL 1164:1174 RESULTS Antioxidant activities in the DPPH (IC50 43.5 and 66.2 μg/mL), FRAP (IC50 312.6 and 568.3 μg/mL) and NO radical scavenging assays (IC50 285.0 and 972.6 μg/mL) were observed in the leaf and bark ethanol extracts, respectively. 28166708 9 47 theme scavenging 1130:1139 arg1 assays 1141:1146 NO radical scavenging assays 1119:1146 NO radical scavenging assays (IC50 285.0 and 972.6 μg/mL) 1119:1175 RESULTS Antioxidant activities in the DPPH (IC50 43.5 and 66.2 μg/mL), FRAP (IC50 312.6 and 568.3 μg/mL) and NO radical scavenging assays (IC50 285.0 and 972.6 μg/mL) were observed in the leaf and bark ethanol extracts, respectively. 28166708 5 48 theme australis 428:436 arg1 bark 417:420 bark 417:420 bark of S. australis (1-100 μg/mL) 417:450 MATERIALS AND METHODS The anti-inflammatory activity of ethanol extracts of the leaf and bark of S. australis (1-100 μg/mL) were studied in lipopolysaccharide/interferon γ stimulated murine macrophages RAW 264.7 cells (24 h incubation) by investigating the release of nitric oxide (NO) and tumour necrosis factor-alpha (TNF-α) and in the TNF-α-induced nuclear factor kappa (NF-κB) assay. 28166708 5 48 theme australis 428:436 arg1 activity 372:379 The anti-inflammatory activity 351:379 The anti-inflammatory activity of ethanol extracts of the leaf 351:411 MATERIALS AND METHODS The anti-inflammatory activity of ethanol extracts of the leaf and bark of S. australis (1-100 μg/mL) were studied in lipopolysaccharide/interferon γ stimulated murine macrophages RAW 264.7 cells (24 h incubation) by investigating the release of nitric oxide (NO) and tumour necrosis factor-alpha (TNF-α) and in the TNF-α-induced nuclear factor kappa (NF-κB) assay. 28166708 12 49 theme rutin 1706:1710 arg1 presence 1673:1680 the presence 1669:1680 the presence of chlorogenic acid and rutin as major compounds 1669:1729 LC-MS/MS revealed the presence of chlorogenic acid and rutin as major compounds. 28166708 12 50 theme major 1715:1719 arg1 compounds 1721:1729 major compounds 1715:1729 major compounds 1715:1729 LC-MS/MS revealed the presence of chlorogenic acid and rutin as major compounds. 28166708 5 51 theme necrosis 625:632 arg1 TNF-α 648:652 TNF-α 648:652 TNF-α 648:652 MATERIALS AND METHODS The anti-inflammatory activity of ethanol extracts of the leaf and bark of S. australis (1-100 μg/mL) were studied in lipopolysaccharide/interferon γ stimulated murine macrophages RAW 264.7 cells (24 h incubation) by investigating the release of nitric oxide (NO) and tumour necrosis factor-alpha (TNF-α) and in the TNF-α-induced nuclear factor kappa (NF-κB) assay. 28166708 5 51 theme necrosis 625:632 arg1 factor-alpha 634:645 tumour necrosis factor-alpha 618:645 tumour necrosis factor-alpha (TNF-α) 618:653 MATERIALS AND METHODS The anti-inflammatory activity of ethanol extracts of the leaf and bark of S. australis (1-100 μg/mL) were studied in lipopolysaccharide/interferon γ stimulated murine macrophages RAW 264.7 cells (24 h incubation) by investigating the release of nitric oxide (NO) and tumour necrosis factor-alpha (TNF-α) and in the TNF-α-induced nuclear factor kappa (NF-κB) assay. 28166708 10 52 theme RAW264.7 1328:1335 arg1 cells 1337:1341 RAW264.7 cells 1328:1341 RAW264.7 cells 1328:1341 Solely the leaf extract showed significant inhibition of NO and TNF-α production in RAW264.7 cells at concentrations of 2 and 100 μg/mL, respectively, and suppression of TNF-α inhibition of NF-κB by 12.8 and 20.4% at concentrations of 50 and 100 μg/mL, respectively. 28166708 5 53 theme RAW 530:532 arg1 cells 540:544 RAW 264.7 cells 530:544 murine macrophages RAW 264.7 cells (24 h incubation) 511:562 MATERIALS AND METHODS The anti-inflammatory activity of ethanol extracts of the leaf and bark of S. australis (1-100 μg/mL) were studied in lipopolysaccharide/interferon γ stimulated murine macrophages RAW 264.7 cells (24 h incubation) by investigating the release of nitric oxide (NO) and tumour necrosis factor-alpha (TNF-α) and in the TNF-α-induced nuclear factor kappa (NF-κB) assay. 28166708 5 54 dep MATERIALS 329:337 arg1 studied 457:463 studied 457:463 were studied in lipopolysaccharide/interferon γ 452:498 MATERIALS AND METHODS The anti-inflammatory activity of ethanol extracts of the leaf and bark of S. australis (1-100 μg/mL) were studied in lipopolysaccharide/interferon γ stimulated murine macrophages RAW 264.7 cells (24 h incubation) by investigating the release of nitric oxide (NO) and tumour necrosis factor-alpha (TNF-α) and in the TNF-α-induced nuclear factor kappa (NF-κB) assay. 28166708 12 55 theme acid 1697:1700 arg1 presence 1673:1680 the presence 1669:1680 the presence of chlorogenic acid and rutin as major compounds 1669:1729 LC-MS/MS revealed the presence of chlorogenic acid and rutin as major compounds. 28166708 10 56 theme 2 1364:1364 arg1 concentrations 1346:1359 concentrations 1346:1359 concentrations of 2 and 100 μg/mL, respectively 1346:1392 Solely the leaf extract showed significant inhibition of NO and TNF-α production in RAW264.7 cells at concentrations of 2 and 100 μg/mL, respectively, and suppression of TNF-α inhibition of NF-κB by 12.8 and 20.4% at concentrations of 50 and 100 μg/mL, respectively. 28166708 7 57 theme Antioxidant 815:825 arg1 activity 827:834 Antioxidant activity 815:834 Antioxidant activity 815:834 Antioxidant activity was determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP) and the NO scavenging assays. 28166708 5 58 theme murine 511:516 arg1 incubation 552:561 24 h incubation 547:561 24 h incubation 547:561 MATERIALS AND METHODS The anti-inflammatory activity of ethanol extracts of the leaf and bark of S. australis (1-100 μg/mL) were studied in lipopolysaccharide/interferon γ stimulated murine macrophages RAW 264.7 cells (24 h incubation) by investigating the release of nitric oxide (NO) and tumour necrosis factor-alpha (TNF-α) and in the TNF-α-induced nuclear factor kappa (NF-κB) assay. 28166708 5 58 theme murine 511:516 arg1 macrophages 518:528 murine macrophages 511:528 murine macrophages RAW 264.7 cells (24 h incubation) 511:562 MATERIALS AND METHODS The anti-inflammatory activity of ethanol extracts of the leaf and bark of S. australis (1-100 μg/mL) were studied in lipopolysaccharide/interferon γ stimulated murine macrophages RAW 264.7 cells (24 h incubation) by investigating the release of nitric oxide (NO) and tumour necrosis factor-alpha (TNF-α) and in the TNF-α-induced nuclear factor kappa (NF-κB) assay. 28166708 5 59 theme TNF-α-induced 666:678 arg1 factor 688:693 the TNF-α-induced nuclear factor 662:693 the TNF-α-induced nuclear factor kappa (NF-κB) assay 662:713 MATERIALS AND METHODS The anti-inflammatory activity of ethanol extracts of the leaf and bark of S. australis (1-100 μg/mL) were studied in lipopolysaccharide/interferon γ stimulated murine macrophages RAW 264.7 cells (24 h incubation) by investigating the release of nitric oxide (NO) and tumour necrosis factor-alpha (TNF-α) and in the TNF-α-induced nuclear factor kappa (NF-κB) assay. 28166708 5 60 dep macrophages 518:528 arg1 cells 540:544 RAW 264.7 cells 530:544 murine macrophages RAW 264.7 cells (24 h incubation) 511:562 MATERIALS AND METHODS The anti-inflammatory activity of ethanol extracts of the leaf and bark of S. australis (1-100 μg/mL) were studied in lipopolysaccharide/interferon γ stimulated murine macrophages RAW 264.7 cells (24 h incubation) by investigating the release of nitric oxide (NO) and tumour necrosis factor-alpha (TNF-α) and in the TNF-α-induced nuclear factor kappa (NF-κB) assay. 28166708 12 61 theme chlorogenic 1685:1695 arg1 acid 1697:1700 chlorogenic acid 1685:1700 chlorogenic acid 1685:1700 LC-MS/MS revealed the presence of chlorogenic acid and rutin as major compounds. 28166708 5 62 theme factor 688:693 arg1 assay 709:713 the TNF-α-induced nuclear factor kappa (NF-κB) assay 662:713 the TNF-α-induced nuclear factor kappa (NF-κB) assay 662:713 MATERIALS AND METHODS The anti-inflammatory activity of ethanol extracts of the leaf and bark of S. australis (1-100 μg/mL) were studied in lipopolysaccharide/interferon γ stimulated murine macrophages RAW 264.7 cells (24 h incubation) by investigating the release of nitric oxide (NO) and tumour necrosis factor-alpha (TNF-α) and in the TNF-α-induced nuclear factor kappa (NF-κB) assay. 28166708 9 63 theme bark 1207:1210 arg1 extracts 1220:1227 the leaf and bark ethanol extracts 1194:1227 extracts 1220:1227 RESULTS Antioxidant activities in the DPPH (IC50 43.5 and 66.2 μg/mL), FRAP (IC50 312.6 and 568.3 μg/mL) and NO radical scavenging assays (IC50 285.0 and 972.6 μg/mL) were observed in the leaf and bark ethanol extracts, respectively. 28166708 5 64 theme leaf 408:411 arg1 extracts 392:399 ethanol extracts 384:399 ethanol extracts of the leaf 384:411 MATERIALS AND METHODS The anti-inflammatory activity of ethanol extracts of the leaf and bark of S. australis (1-100 μg/mL) were studied in lipopolysaccharide/interferon γ stimulated murine macrophages RAW 264.7 cells (24 h incubation) by investigating the release of nitric oxide (NO) and tumour necrosis factor-alpha (TNF-α) and in the TNF-α-induced nuclear factor kappa (NF-κB) assay. 28166708 0 65 theme australis 82:90 arg1 activities 59:68 Potential anti-inflammatory, antioxidant and antimicrobial activities 0:68 Potential anti-inflammatory, antioxidant and antimicrobial activities of Sambucus australis 0:90 Potential anti-inflammatory, antioxidant and antimicrobial activities of Sambucus australis. 28166708 5 66 theme ethanol 384:390 arg1 extracts 392:399 ethanol extracts 384:399 ethanol extracts of the leaf 384:411 MATERIALS AND METHODS The anti-inflammatory activity of ethanol extracts of the leaf and bark of S. australis (1-100 μg/mL) were studied in lipopolysaccharide/interferon γ stimulated murine macrophages RAW 264.7 cells (24 h incubation) by investigating the release of nitric oxide (NO) and tumour necrosis factor-alpha (TNF-α) and in the TNF-α-induced nuclear factor kappa (NF-κB) assay. 28166708 3 67 theme folk 170:173 arg1 medicine 175:182 Brazilian folk medicine 160:182 Brazilian folk medicine 160:182 (Adoxaceae) is used in Brazilian folk medicine to treat inflammatory disorders. 28166708 13 68 theme anti-inflammatory 1843:1858 arg1 effects 1860:1866 prominent anti-inflammatory effects 1833:1866 prominent anti-inflammatory effects 1833:1866 DISCUSSION AND CONCLUSION The results indicate that the ethanol leaf extract of S. australis exhibit prominent anti-inflammatory effects. 28166708 5 69 theme tumour 618:623 arg1 TNF-α 648:652 TNF-α 648:652 TNF-α 648:652 MATERIALS AND METHODS The anti-inflammatory activity of ethanol extracts of the leaf and bark of S. australis (1-100 μg/mL) were studied in lipopolysaccharide/interferon γ stimulated murine macrophages RAW 264.7 cells (24 h incubation) by investigating the release of nitric oxide (NO) and tumour necrosis factor-alpha (TNF-α) and in the TNF-α-induced nuclear factor kappa (NF-κB) assay. 28166708 5 69 theme tumour 618:623 arg1 factor-alpha 634:645 tumour necrosis factor-alpha 618:645 tumour necrosis factor-alpha (TNF-α) 618:653 MATERIALS AND METHODS The anti-inflammatory activity of ethanol extracts of the leaf and bark of S. australis (1-100 μg/mL) were studied in lipopolysaccharide/interferon γ stimulated murine macrophages RAW 264.7 cells (24 h incubation) by investigating the release of nitric oxide (NO) and tumour necrosis factor-alpha (TNF-α) and in the TNF-α-induced nuclear factor kappa (NF-κB) assay. 28166708 10 70 from inhibition 1287:1296 arg1 concentrations 1346:1359 concentrations 1346:1359 concentrations of 2 and 100 μg/mL, respectively 1346:1392 Solely the leaf extract showed significant inhibition of NO and TNF-α production in RAW264.7 cells at concentrations of 2 and 100 μg/mL, respectively, and suppression of TNF-α inhibition of NF-κB by 12.8 and 20.4% at concentrations of 50 and 100 μg/mL, respectively. 28166708 10 70 from inhibition 1287:1296 arg1 cells 1337:1341 RAW264.7 cells 1328:1341 RAW264.7 cells 1328:1341 Solely the leaf extract showed significant inhibition of NO and TNF-α production in RAW264.7 cells at concentrations of 2 and 100 μg/mL, respectively, and suppression of TNF-α inhibition of NF-κB by 12.8 and 20.4% at concentrations of 50 and 100 μg/mL, respectively. 28166708 10 71 theme TNF-α 1414:1418 arg1 inhibition 1420:1429 TNF-α inhibition 1414:1429 TNF-α inhibition of NF-κB by 12.8 and 20.4% at concentrations of 50 and 100 μg/mL, respectively 1414:1508 Solely the leaf extract showed significant inhibition of NO and TNF-α production in RAW264.7 cells at concentrations of 2 and 100 μg/mL, respectively, and suppression of TNF-α inhibition of NF-κB by 12.8 and 20.4% at concentrations of 50 and 100 μg/mL, respectively. 28166708 3 72 theme inflammatory 193:204 arg1 disorders 206:214 inflammatory disorders 193:214 inflammatory disorders 193:214 (Adoxaceae) is used in Brazilian folk medicine to treat inflammatory disorders. 28166708 0 73 theme anti-inflammatory 10:26 arg1 activities 59:68 Potential anti-inflammatory, antioxidant and antimicrobial activities 0:68 Potential anti-inflammatory, antioxidant and antimicrobial activities of Sambucus australis 0:90 Potential anti-inflammatory, antioxidant and antimicrobial activities of Sambucus australis. 28166708 5 74 theme nitric 596:601 arg1 oxide 603:607 nitric oxide 596:607 nitric oxide (NO) 596:612 MATERIALS AND METHODS The anti-inflammatory activity of ethanol extracts of the leaf and bark of S. australis (1-100 μg/mL) were studied in lipopolysaccharide/interferon γ stimulated murine macrophages RAW 264.7 cells (24 h incubation) by investigating the release of nitric oxide (NO) and tumour necrosis factor-alpha (TNF-α) and in the TNF-α-induced nuclear factor kappa (NF-κB) assay. 28166708 5 74 theme nitric 596:601 arg1 NO 610:611 NO 610:611 NO 610:611 MATERIALS AND METHODS The anti-inflammatory activity of ethanol extracts of the leaf and bark of S. australis (1-100 μg/mL) were studied in lipopolysaccharide/interferon γ stimulated murine macrophages RAW 264.7 cells (24 h incubation) by investigating the release of nitric oxide (NO) and tumour necrosis factor-alpha (TNF-α) and in the TNF-α-induced nuclear factor kappa (NF-κB) assay. 28166708 1 75 theme Sambucus 101:108 arg1 australis 110:118 CONTEXT Sambucus australis 93:118 CONTEXT Sambucus australis 93:118 CONTEXT Sambucus australis Cham. 28166708 10 76 from NO 1301:1302 arg1 cells 1337:1341 RAW264.7 cells 1328:1341 RAW264.7 cells 1328:1341 Solely the leaf extract showed significant inhibition of NO and TNF-α production in RAW264.7 cells at concentrations of 2 and 100 μg/mL, respectively, and suppression of TNF-α inhibition of NF-κB by 12.8 and 20.4% at concentrations of 50 and 100 μg/mL, respectively. 28166708 0 77 theme antioxidant 29:39 arg1 activities 59:68 Potential anti-inflammatory, antioxidant and antimicrobial activities 0:68 Potential anti-inflammatory, antioxidant and antimicrobial activities of Sambucus australis 0:90 Potential anti-inflammatory, antioxidant and antimicrobial activities of Sambucus australis. 28166708 7 78 theme NO 941:942 arg1 assays 955:960 the NO scavenging assays 937:960 the NO scavenging assays 937:960 Antioxidant activity was determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP) and the NO scavenging assays. 28166708 6 79 theme inhibitory 724:733 arg1 MIC 750:752 MIC 750:752 MIC 750:752 Minimum inhibitory concentration (MIC) was determined by the microdilution test (24 h incubation). 28166708 6 79 theme inhibitory 724:733 arg1 concentration 735:747 Minimum inhibitory concentration 716:747 Minimum inhibitory concentration (MIC) 716:753 Minimum inhibitory concentration (MIC) was determined by the microdilution test (24 h incubation). 28166708 10 80 theme leaf 1255:1258 arg1 extract 1260:1266 Solely the leaf extract 1244:1266 Solely the leaf extract 1244:1266 Solely the leaf extract showed significant inhibition of NO and TNF-α production in RAW264.7 cells at concentrations of 2 and 100 μg/mL, respectively, and suppression of TNF-α inhibition of NF-κB by 12.8 and 20.4% at concentrations of 50 and 100 μg/mL, respectively. 28166708 0 81 theme antimicrobial 45:57 arg1 activities 59:68 Potential anti-inflammatory, antioxidant and antimicrobial activities 0:68 Potential anti-inflammatory, antioxidant and antimicrobial activities of Sambucus australis 0:90 Potential anti-inflammatory, antioxidant and antimicrobial activities of Sambucus australis. 28166708 10 82 from concentrations 1461:1474 arg1 % 1456:1456 12.8 and 20.4% 1443:1456 12.8 and 20.4% at concentrations of 50 1443:1480 Solely the leaf extract showed significant inhibition of NO and TNF-α production in RAW264.7 cells at concentrations of 2 and 100 μg/mL, respectively, and suppression of TNF-α inhibition of NF-κB by 12.8 and 20.4% at concentrations of 50 and 100 μg/mL, respectively. 28166708 10 82 from concentrations 1461:1474 arg1 100 μg/mL 1486:1494 100 μg/mL 1486:1494 100 μg/mL 1486:1494 Solely the leaf extract showed significant inhibition of NO and TNF-α production in RAW264.7 cells at concentrations of 2 and 100 μg/mL, respectively, and suppression of TNF-α inhibition of NF-κB by 12.8 and 20.4% at concentrations of 50 and 100 μg/mL, respectively. 28166708 10 83 theme NO 1301:1302 arg1 inhibition 1287:1296 significant inhibition 1275:1296 significant inhibition of NO and TNF-α production in RAW264.7 cells at concentrations of 2 and 100 μg/mL, respectively 1275:1392 Solely the leaf extract showed significant inhibition of NO and TNF-α production in RAW264.7 cells at concentrations of 2 and 100 μg/mL, respectively, and suppression of TNF-α inhibition of NF-κB by 12.8 and 20.4% at concentrations of 50 and 100 μg/mL, respectively. 28166708 10 83 theme NO 1301:1302 arg1 suppression 1399:1409 suppression 1399:1409 suppression of TNF-α inhibition of NF-κB by 12.8 and 20.4% at concentrations of 50 and 100 μg/mL, respectively 1399:1508 Solely the leaf extract showed significant inhibition of NO and TNF-α production in RAW264.7 cells at concentrations of 2 and 100 μg/mL, respectively, and suppression of TNF-α inhibition of NF-κB by 12.8 and 20.4% at concentrations of 50 and 100 μg/mL, respectively. 28166708 13 84 dep DISCUSSION 1732:1741 arg1 results 1762:1768 The results 1758:1768 The results 1758:1768 DISCUSSION AND CONCLUSION The results indicate that the ethanol leaf extract of S. australis exhibit prominent anti-inflammatory effects. 28166708 10 85 from cells 1337:1341 arg1 inhibition 1287:1296 significant inhibition 1275:1296 significant inhibition of NO and TNF-α production in RAW264.7 cells at concentrations of 2 and 100 μg/mL, respectively 1275:1392 Solely the leaf extract showed significant inhibition of NO and TNF-α production in RAW264.7 cells at concentrations of 2 and 100 μg/mL, respectively, and suppression of TNF-α inhibition of NF-κB by 12.8 and 20.4% at concentrations of 50 and 100 μg/mL, respectively. 28166708 10 85 from cells 1337:1341 arg1 suppression 1399:1409 suppression 1399:1409 suppression of TNF-α inhibition of NF-κB by 12.8 and 20.4% at concentrations of 50 and 100 μg/mL, respectively 1399:1508 Solely the leaf extract showed significant inhibition of NO and TNF-α production in RAW264.7 cells at concentrations of 2 and 100 μg/mL, respectively, and suppression of TNF-α inhibition of NF-κB by 12.8 and 20.4% at concentrations of 50 and 100 μg/mL, respectively. 28166708 7 86 theme antioxidant 908:918 arg1 FRAP 927:930 FRAP 927:930 FRAP 927:930 Antioxidant activity was determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP) and the NO scavenging assays. 28166708 7 86 theme antioxidant 908:918 arg1 power 920:924 ferric reducing antioxidant power 892:924 ferric reducing antioxidant power (FRAP) 892:931 Antioxidant activity was determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP) and the NO scavenging assays. 28166708 10 87 from concentrations 1346:1359 arg1 NO 1301:1302 NO 1301:1302 NO 1301:1302 Solely the leaf extract showed significant inhibition of NO and TNF-α production in RAW264.7 cells at concentrations of 2 and 100 μg/mL, respectively, and suppression of TNF-α inhibition of NF-κB by 12.8 and 20.4% at concentrations of 50 and 100 μg/mL, respectively. 28166708 10 87 from concentrations 1346:1359 arg1 production 1314:1323 TNF-α production 1308:1323 TNF-α production 1308:1323 Solely the leaf extract showed significant inhibition of NO and TNF-α production in RAW264.7 cells at concentrations of 2 and 100 μg/mL, respectively, and suppression of TNF-α inhibition of NF-κB by 12.8 and 20.4% at concentrations of 50 and 100 μg/mL, respectively. 28166708 10 87 from concentrations 1346:1359 arg1 inhibition 1287:1296 significant inhibition 1275:1296 significant inhibition of NO and TNF-α production in RAW264.7 cells at concentrations of 2 and 100 μg/mL, respectively 1275:1392 Solely the leaf extract showed significant inhibition of NO and TNF-α production in RAW264.7 cells at concentrations of 2 and 100 μg/mL, respectively, and suppression of TNF-α inhibition of NF-κB by 12.8 and 20.4% at concentrations of 50 and 100 μg/mL, respectively. 28166708 10 87 from concentrations 1346:1359 arg1 suppression 1399:1409 suppression 1399:1409 suppression of TNF-α inhibition of NF-κB by 12.8 and 20.4% at concentrations of 50 and 100 μg/mL, respectively 1399:1508 Solely the leaf extract showed significant inhibition of NO and TNF-α production in RAW264.7 cells at concentrations of 2 and 100 μg/mL, respectively, and suppression of TNF-α inhibition of NF-κB by 12.8 and 20.4% at concentrations of 50 and 100 μg/mL, respectively. 28166708 9 88 located observed 1182:1189 arg1 leaf 1198:1201 the leaf and bark ethanol extracts 1194:1227 leaf 1198:1201 RESULTS Antioxidant activities in the DPPH (IC50 43.5 and 66.2 μg/mL), FRAP (IC50 312.6 and 568.3 μg/mL) and NO radical scavenging assays (IC50 285.0 and 972.6 μg/mL) were observed in the leaf and bark ethanol extracts, respectively. 28166708 9 88 located observed 1182:1189 arg2 assays 1141:1146 NO radical scavenging assays 1119:1146 NO radical scavenging assays (IC50 285.0 and 972.6 μg/mL) 1119:1175 RESULTS Antioxidant activities in the DPPH (IC50 43.5 and 66.2 μg/mL), FRAP (IC50 312.6 and 568.3 μg/mL) and NO radical scavenging assays (IC50 285.0 and 972.6 μg/mL) were observed in the leaf and bark ethanol extracts, respectively. 28166708 9 88 located observed 1182:1189 arg2 IC50 1149:1152 IC50 285.0 1149:1158 IC50 285.0 1149:1158 RESULTS Antioxidant activities in the DPPH (IC50 43.5 and 66.2 μg/mL), FRAP (IC50 312.6 and 568.3 μg/mL) and NO radical scavenging assays (IC50 285.0 and 972.6 μg/mL) were observed in the leaf and bark ethanol extracts, respectively. 28166708 9 88 located observed 1182:1189 arg2 RESULTS 1010:1016 RESULTS Antioxidant activities in the DPPH (IC50 43.5 and 66.2 μg/mL), FRAP (IC50 312.6 and 568.3 μg/mL) and NO radical scavenging assays (IC50 285.0 and 972.6 μg/mL) 1010:1175 RESULTS 1010:1016 RESULTS Antioxidant activities in the DPPH (IC50 43.5 and 66.2 μg/mL), FRAP (IC50 312.6 and 568.3 μg/mL) and NO radical scavenging assays (IC50 285.0 and 972.6 μg/mL) were observed in the leaf and bark ethanol extracts, respectively. 28166708 9 88 located observed 1182:1189 arg2 972.6 μg/mL 1164:1174 972.6 μg/mL 1164:1174 972.6 μg/mL 1164:1174 RESULTS Antioxidant activities in the DPPH (IC50 43.5 and 66.2 μg/mL), FRAP (IC50 312.6 and 568.3 μg/mL) and NO radical scavenging assays (IC50 285.0 and 972.6 μg/mL) were observed in the leaf and bark ethanol extracts, respectively. 28166708 9 88 located observed 1182:1189 arg1 extracts 1220:1227 the leaf and bark ethanol extracts 1194:1227 extracts 1220:1227 RESULTS Antioxidant activities in the DPPH (IC50 43.5 and 66.2 μg/mL), FRAP (IC50 312.6 and 568.3 μg/mL) and NO radical scavenging assays (IC50 285.0 and 972.6 μg/mL) were observed in the leaf and bark ethanol extracts, respectively. 28166708 7 89 theme ferric 892:897 arg1 FRAP 927:930 FRAP 927:930 FRAP 927:930 Antioxidant activity was determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP) and the NO scavenging assays. 28166708 7 89 theme ferric 892:897 arg1 power 920:924 ferric reducing antioxidant power 892:924 ferric reducing antioxidant power (FRAP) 892:931 Antioxidant activity was determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP) and the NO scavenging assays. 28166708 10 90 theme 50 1479:1480 arg1 concentrations 1461:1474 concentrations 1461:1474 concentrations of 50 1461:1480 Solely the leaf extract showed significant inhibition of NO and TNF-α production in RAW264.7 cells at concentrations of 2 and 100 μg/mL, respectively, and suppression of TNF-α inhibition of NF-κB by 12.8 and 20.4% at concentrations of 50 and 100 μg/mL, respectively. 28166708 11 91 theme MIC 1593:1595 arg1 typhimurium 1580:1590 Salmonella typhimurium 1569:1590 Salmonella typhimurium (MIC 250 μg/mL) 1569:1606 The extract also exhibited antibacterial activity against Salmonella typhimurium (MIC 250 μg/mL) and Klebsiella pneumoniae (MIC 250 μg/mL). 28166708 11 91 theme MIC 1593:1595 arg1 250 μg/mL 1597:1605 MIC 250 μg/mL 1593:1605 MIC 250 μg/mL 1593:1605 The extract also exhibited antibacterial activity against Salmonella typhimurium (MIC 250 μg/mL) and Klebsiella pneumoniae (MIC 250 μg/mL). 28166708 10 92 theme TNF-α 1308:1312 arg1 production 1314:1323 TNF-α production 1308:1323 TNF-α production 1308:1323 Solely the leaf extract showed significant inhibition of NO and TNF-α production in RAW264.7 cells at concentrations of 2 and 100 μg/mL, respectively, and suppression of TNF-α inhibition of NF-κB by 12.8 and 20.4% at concentrations of 50 and 100 μg/mL, respectively. 26212688 11 0 theme population 1983:1992 arg1 population 1983:1992 the freeze-sensitive bacterial population 1952:1992 the freeze-sensitive bacterial population 1952:1992 Freezing and thawing processes induced losses of membrane integrity and cell viability in more than 90% of the freeze-sensitive bacterial population. 26212688 11 0 theme population 1983:1992 arg1 % 1947:1947 more than 90% 1935:1947 more than 90% of the freeze-sensitive bacterial population 1935:1992 Freezing and thawing processes induced losses of membrane integrity and cell viability in more than 90% of the freeze-sensitive bacterial population. 26212688 9 1 theme secondary 1508:1516 arg1 structure 1518:1526 an α-helix secondary structure 1497:1526 an α-helix secondary structure 1497:1526 SR-FTIR results indicated that before freezing, freeze-resistant cells grown in a rich medium presented a high content of CH3 groups from lipid chains, of cell proteins in an α-helix secondary structure and of charged polymers such as teichoic and lipoteichoic acids that constitute the Gram-positive bacterial wall. 26212688 8 2 theme particular 1267:1276 arg1 focus 1278:1282 particular focus 1267:1282 particular focus on lipids, proteins and polysaccharides 1267:1322 Principal component analysis was used to evaluate changes in cell composition, with particular focus on lipids, proteins and polysaccharides. 26212688 11 3 theme bacterial 1973:1981 arg1 population 1983:1992 the freeze-sensitive bacterial population 1952:1992 the freeze-sensitive bacterial population 1952:1992 Freezing and thawing processes induced losses of membrane integrity and cell viability in more than 90% of the freeze-sensitive bacterial population. 26212688 6 4 theme sub-cellular 974:985 arg1 resolution 995:1004 sub-cellular spatial resolution 974:1004 sub-cellular spatial resolution 974:1004 Infrared spectra of individual bacteria produced by applying different fermentation and freezing conditions were acquired using synchrotron radiation-based Fourier-transform infrared (SR-FTIR) microspectroscopy to achieve sub-cellular spatial resolution. 26212688 2 5 used used 254:257 arg2 concentrates 195:206 Frozen concentrates 188:206 Frozen concentrates of lactic acid bacteria (LAB) 188:236 Frozen concentrates of lactic acid bacteria (LAB) are extensively used for manufacturing food, probiotic products and for green chemistry and medical applications. 26212688 5 6 theme cell 646:649 arg1 scale 651:655 the cell scale 642:655 the cell scale 642:655 Our objective was to investigate the biochemical and physiological changes in a LAB model at the cell scale following fermentation and freezing in order to identify cellular biomarkers of cryotolerance. 26212688 6 7 theme freezing 840:847 arg1 conditions 849:858 different fermentation and freezing conditions 813:858 conditions 849:858 Infrared spectra of individual bacteria produced by applying different fermentation and freezing conditions were acquired using synchrotron radiation-based Fourier-transform infrared (SR-FTIR) microspectroscopy to achieve sub-cellular spatial resolution. 26212688 2 8 theme food 277:280 arg1 products 293:300 food, probiotic products 277:300 food, probiotic products 277:300 Frozen concentrates of lactic acid bacteria (LAB) are extensively used for manufacturing food, probiotic products and for green chemistry and medical applications. 26212688 9 9 theme charged 1535:1541 arg1 polymers 1543:1550 charged polymers 1535:1550 charged polymers such as teichoic and lipoteichoic acids that constitute the Gram-positive bacterial wall 1535:1639 SR-FTIR results indicated that before freezing, freeze-resistant cells grown in a rich medium presented a high content of CH3 groups from lipid chains, of cell proteins in an α-helix secondary structure and of charged polymers such as teichoic and lipoteichoic acids that constitute the Gram-positive bacterial wall. 26212688 9 9 theme charged 1535:1541 arg1 acids 1586:1590 teichoic and lipoteichoic acids 1560:1590 acids 1586:1590 SR-FTIR results indicated that before freezing, freeze-resistant cells grown in a rich medium presented a high content of CH3 groups from lipid chains, of cell proteins in an α-helix secondary structure and of charged polymers such as teichoic and lipoteichoic acids that constitute the Gram-positive bacterial wall. 26212688 12 10 theme phospholipids 2090:2102 arg1 modification 2060:2071 biochemical modification 2048:2071 biochemical modification of cell membrane phospholipids 2048:2102 These damages leading to cell death were ascribed to biochemical modification of cell membrane phospholipids, in particular a rigidification of the cytoplasmic membrane following freezing. 26212688 11 11 theme cell 1917:1920 arg1 viability 1922:1930 cell viability 1917:1930 cell viability 1917:1930 Freezing and thawing processes induced losses of membrane integrity and cell viability in more than 90% of the freeze-sensitive bacterial population. 26212688 9 12 theme SR-FTIR 1325:1331 arg1 results 1333:1339 SR-FTIR results 1325:1339 SR-FTIR results 1325:1339 SR-FTIR results indicated that before freezing, freeze-resistant cells grown in a rich medium presented a high content of CH3 groups from lipid chains, of cell proteins in an α-helix secondary structure and of charged polymers such as teichoic and lipoteichoic acids that constitute the Gram-positive bacterial wall. 26212688 2 13 theme green 310:314 arg1 chemistry 316:324 green chemistry 310:324 green chemistry 310:324 Frozen concentrates of lactic acid bacteria (LAB) are extensively used for manufacturing food, probiotic products and for green chemistry and medical applications. 26212688 11 14 theme integrity 1903:1911 arg1 losses 1884:1889 losses 1884:1889 losses of membrane integrity and cell viability 1884:1930 Freezing and thawing processes induced losses of membrane integrity and cell viability in more than 90% of the freeze-sensitive bacterial population. 26212688 11 15 dep Freezing 1845:1852 arg1 processes 1866:1874 processes 1866:1874 processes 1866:1874 Freezing and thawing processes induced losses of membrane integrity and cell viability in more than 90% of the freeze-sensitive bacterial population. 26212688 9 16 theme teichoic 1560:1567 arg1 acids 1586:1590 teichoic and lipoteichoic acids 1560:1590 acids 1586:1590 SR-FTIR results indicated that before freezing, freeze-resistant cells grown in a rich medium presented a high content of CH3 groups from lipid chains, of cell proteins in an α-helix secondary structure and of charged polymers such as teichoic and lipoteichoic acids that constitute the Gram-positive bacterial wall. 26212688 10 17 theme cells 1756:1760 arg1 cluster 1735:1741 the cluster 1731:1741 the cluster of resistant cells, which was ascribed to the diversity of potential substrates in the growth medium 1731:1842 Moreover, SR-FTIR microspectroscopy made it possible to reveal cell heterogeneity within the cluster of resistant cells, which was ascribed to the diversity of potential substrates in the growth medium. 26212688 7 18 theme first 1171:1175 arg1 time 1177:1180 the first time 1167:1180 the first time 1167:1180 Fluorescent microscopy was concomitantly assessed, thus making possible to simultaneously analyse the biochemistry and physiological state of a single cell for the first time. 26212688 9 19 theme lipoteichoic 1573:1584 arg1 acids 1586:1590 teichoic and lipoteichoic acids 1560:1590 acids 1586:1590 SR-FTIR results indicated that before freezing, freeze-resistant cells grown in a rich medium presented a high content of CH3 groups from lipid chains, of cell proteins in an α-helix secondary structure and of charged polymers such as teichoic and lipoteichoic acids that constitute the Gram-positive bacterial wall. 26212688 12 20 theme cell 2076:2079 arg1 phospholipids 2090:2102 cell membrane phospholipids 2076:2102 cell membrane phospholipids 2076:2102 These damages leading to cell death were ascribed to biochemical modification of cell membrane phospholipids, in particular a rigidification of the cytoplasmic membrane following freezing. 26212688 4 21 theme homogeneous 465:475 arg1 populations 487:497 homogeneous bacterial populations 465:497 homogeneous bacterial populations 465:497 Producing homogeneous bacterial populations with high cryotolerance remains a real challenge. 26212688 9 22 from structure 1518:1526 arg1 chains 1469:1474 lipid chains 1463:1474 lipid chains 1463:1474 SR-FTIR results indicated that before freezing, freeze-resistant cells grown in a rich medium presented a high content of CH3 groups from lipid chains, of cell proteins in an α-helix secondary structure and of charged polymers such as teichoic and lipoteichoic acids that constitute the Gram-positive bacterial wall. 26212688 7 23 theme single 1151:1156 arg1 cell 1158:1161 a single cell 1149:1161 a single cell 1149:1161 Fluorescent microscopy was concomitantly assessed, thus making possible to simultaneously analyse the biochemistry and physiological state of a single cell for the first time. 26212688 0 24 theme combined 62:69 arg1 infrared 83:90 combined synchrotron infrared 62:90 combined synchrotron infrared 62:90 Understanding the cryotolerance of lactic acid bacteria using combined synchrotron infrared and fluorescence microscopies. 26212688 13 25 theme freeze-resistant 2200:2215 arg1 cells 2217:2221 the freeze-resistant cells 2196:2221 the freeze-resistant cells 2196:2221 Furthermore the freeze-resistant cells remained viable after freezing and thawing but a modification of protein secondary structure was detected by SR-FTIR analysis. 26212688 9 26 theme bacterial 1626:1634 arg1 wall 1636:1639 the Gram-positive bacterial wall 1608:1639 the Gram-positive bacterial wall 1608:1639 SR-FTIR results indicated that before freezing, freeze-resistant cells grown in a rich medium presented a high content of CH3 groups from lipid chains, of cell proteins in an α-helix secondary structure and of charged polymers such as teichoic and lipoteichoic acids that constitute the Gram-positive bacterial wall. 26212688 5 27 theme cellular 714:721 arg1 biomarkers 723:732 cellular biomarkers 714:732 cellular biomarkers of cryotolerance 714:749 Our objective was to investigate the biochemical and physiological changes in a LAB model at the cell scale following fermentation and freezing in order to identify cellular biomarkers of cryotolerance. 26212688 9 28 theme rich 1407:1410 arg1 medium 1412:1417 a rich medium 1405:1417 a rich medium 1405:1417 SR-FTIR results indicated that before freezing, freeze-resistant cells grown in a rich medium presented a high content of CH3 groups from lipid chains, of cell proteins in an α-helix secondary structure and of charged polymers such as teichoic and lipoteichoic acids that constitute the Gram-positive bacterial wall. 26212688 4 29 theme real 533:536 arg1 challenge 538:546 a real challenge 531:546 a real challenge 531:546 Producing homogeneous bacterial populations with high cryotolerance remains a real challenge. 26212688 0 30 theme fluorescence 96:107 arg1 microscopies 109:120 fluorescence microscopies 96:120 fluorescence microscopies 96:120 Understanding the cryotolerance of lactic acid bacteria using combined synchrotron infrared and fluorescence microscopies. 26212688 9 31 from chains 1469:1474 arg1 structure 1518:1526 an α-helix secondary structure 1497:1526 an α-helix secondary structure 1497:1526 SR-FTIR results indicated that before freezing, freeze-resistant cells grown in a rich medium presented a high content of CH3 groups from lipid chains, of cell proteins in an α-helix secondary structure and of charged polymers such as teichoic and lipoteichoic acids that constitute the Gram-positive bacterial wall. 26212688 3 32 theme cell 443:446 arg1 death 448:452 significant cell death 431:452 significant cell death 431:452 However, the freezing and thawing processes cause cell injuries that result in significant cell death. 26212688 9 33 theme high 1431:1434 arg1 content 1436:1442 a high content 1429:1442 a high content of CH3 groups 1429:1456 SR-FTIR results indicated that before freezing, freeze-resistant cells grown in a rich medium presented a high content of CH3 groups from lipid chains, of cell proteins in an α-helix secondary structure and of charged polymers such as teichoic and lipoteichoic acids that constitute the Gram-positive bacterial wall. 26212688 4 34 theme high 504:507 arg1 cryotolerance 509:521 high cryotolerance 504:521 high cryotolerance 504:521 Producing homogeneous bacterial populations with high cryotolerance remains a real challenge. 26212688 5 35 from scale 651:655 arg1 changes 616:622 the biochemical and physiological changes 582:622 the biochemical and physiological changes in a LAB model at the cell scale 582:655 Our objective was to investigate the biochemical and physiological changes in a LAB model at the cell scale following fermentation and freezing in order to identify cellular biomarkers of cryotolerance. 26212688 9 36 theme groups 1451:1456 arg1 content 1436:1442 a high content 1429:1442 a high content of CH3 groups 1429:1456 SR-FTIR results indicated that before freezing, freeze-resistant cells grown in a rich medium presented a high content of CH3 groups from lipid chains, of cell proteins in an α-helix secondary structure and of charged polymers such as teichoic and lipoteichoic acids that constitute the Gram-positive bacterial wall. 26212688 8 37 theme Principal 1183:1191 arg1 analysis 1203:1210 Principal component analysis 1183:1210 Principal component analysis 1183:1210 Principal component analysis was used to evaluate changes in cell composition, with particular focus on lipids, proteins and polysaccharides. 26212688 13 38 theme protein 2288:2294 arg1 structure 2306:2314 protein secondary structure 2288:2314 protein secondary structure 2288:2314 Furthermore the freeze-resistant cells remained viable after freezing and thawing but a modification of protein secondary structure was detected by SR-FTIR analysis. 26212688 14 39 theme bimodal 2405:2411 arg1 analysis 2413:2420 bimodal analysis 2405:2420 bimodal analysis 2405:2420 These results highlighted the potential application of bimodal analysis by SR-FTIR and fluorescence microscopy to increase our knowledge about mechanisms related to cell damage. 26212688 2 40 theme Frozen 188:193 arg1 concentrates 195:206 Frozen concentrates 188:206 Frozen concentrates of lactic acid bacteria (LAB) 188:236 Frozen concentrates of lactic acid bacteria (LAB) are extensively used for manufacturing food, probiotic products and for green chemistry and medical applications. 26212688 7 41 dep biochemistry 1109:1120 arg1 the 1105:1107 the 1105:1107 the 1105:1107 Fluorescent microscopy was concomitantly assessed, thus making possible to simultaneously analyse the biochemistry and physiological state of a single cell for the first time. 26212688 0 42 theme lactic 35:40 arg1 bacteria 47:54 lactic acid bacteria 35:54 lactic acid bacteria using combined synchrotron infrared and fluorescence microscopies 35:120 Understanding the cryotolerance of lactic acid bacteria using combined synchrotron infrared and fluorescence microscopies. 26212688 9 43 theme lipid 1463:1467 arg1 chains 1469:1474 lipid chains 1463:1474 lipid chains 1463:1474 SR-FTIR results indicated that before freezing, freeze-resistant cells grown in a rich medium presented a high content of CH3 groups from lipid chains, of cell proteins in an α-helix secondary structure and of charged polymers such as teichoic and lipoteichoic acids that constitute the Gram-positive bacterial wall. 26212688 6 44 theme SR-FTIR 936:942 arg1 microspectroscopy 945:961 synchrotron radiation-based Fourier-transform infrared (SR-FTIR) microspectroscopy 880:961 synchrotron radiation-based Fourier-transform infrared (SR-FTIR) microspectroscopy 880:961 Infrared spectra of individual bacteria produced by applying different fermentation and freezing conditions were acquired using synchrotron radiation-based Fourier-transform infrared (SR-FTIR) microspectroscopy to achieve sub-cellular spatial resolution. 26212688 3 45 theme cell 402:405 arg1 injuries 407:414 cell injuries 402:414 cell injuries that result in significant cell death 402:452 However, the freezing and thawing processes cause cell injuries that result in significant cell death. 26212688 0 46 theme bacteria 47:54 arg1 cryotolerance 18:30 the cryotolerance 14:30 the cryotolerance of lactic acid bacteria using combined synchrotron infrared and fluorescence microscopies 14:120 Understanding the cryotolerance of lactic acid bacteria using combined synchrotron infrared and fluorescence microscopies. 26212688 6 47 theme infrared 926:933 arg1 microspectroscopy 945:961 synchrotron radiation-based Fourier-transform infrared (SR-FTIR) microspectroscopy 880:961 synchrotron radiation-based Fourier-transform infrared (SR-FTIR) microspectroscopy 880:961 Infrared spectra of individual bacteria produced by applying different fermentation and freezing conditions were acquired using synchrotron radiation-based Fourier-transform infrared (SR-FTIR) microspectroscopy to achieve sub-cellular spatial resolution. 26212688 2 48 theme acid 218:221 arg1 LAB 233:235 LAB 233:235 LAB 233:235 Frozen concentrates of lactic acid bacteria (LAB) are extensively used for manufacturing food, probiotic products and for green chemistry and medical applications. 26212688 2 48 theme acid 218:221 arg1 bacteria 223:230 lactic acid bacteria 211:230 lactic acid bacteria (LAB) 211:236 Frozen concentrates of lactic acid bacteria (LAB) are extensively used for manufacturing food, probiotic products and for green chemistry and medical applications. 26212688 6 49 theme bacteria 783:790 arg1 spectra 761:767 Infrared spectra 752:767 Infrared spectra of individual bacteria produced by applying different fermentation and freezing conditions 752:858 Infrared spectra of individual bacteria produced by applying different fermentation and freezing conditions were acquired using synchrotron radiation-based Fourier-transform infrared (SR-FTIR) microspectroscopy to achieve sub-cellular spatial resolution. 26212688 2 50 theme medical 330:336 arg1 applications 338:349 medical applications 330:349 medical applications 330:349 Frozen concentrates of lactic acid bacteria (LAB) are extensively used for manufacturing food, probiotic products and for green chemistry and medical applications. 26212688 9 51 theme cell 1480:1483 arg1 proteins 1485:1492 cell proteins 1480:1492 cell proteins in an α-helix secondary structure 1480:1526 SR-FTIR results indicated that before freezing, freeze-resistant cells grown in a rich medium presented a high content of CH3 groups from lipid chains, of cell proteins in an α-helix secondary structure and of charged polymers such as teichoic and lipoteichoic acids that constitute the Gram-positive bacterial wall. 26212688 9 52 from proteins 1485:1492 arg1 structure 1518:1526 an α-helix secondary structure 1497:1526 an α-helix secondary structure 1497:1526 SR-FTIR results indicated that before freezing, freeze-resistant cells grown in a rich medium presented a high content of CH3 groups from lipid chains, of cell proteins in an α-helix secondary structure and of charged polymers such as teichoic and lipoteichoic acids that constitute the Gram-positive bacterial wall. 26212688 6 53 theme radiation-based 892:906 arg1 microspectroscopy 945:961 synchrotron radiation-based Fourier-transform infrared (SR-FTIR) microspectroscopy 880:961 synchrotron radiation-based Fourier-transform infrared (SR-FTIR) microspectroscopy 880:961 Infrared spectra of individual bacteria produced by applying different fermentation and freezing conditions were acquired using synchrotron radiation-based Fourier-transform infrared (SR-FTIR) microspectroscopy to achieve sub-cellular spatial resolution. 26212688 1 54 theme different 162:170 arg1 types 172:176 different types 162:176 different types of cells 162:185 Freezing is widely used for preserving different types of cells. 26212688 13 55 theme SR-FTIR 2332:2338 arg1 analysis 2340:2347 SR-FTIR analysis 2332:2347 SR-FTIR analysis 2332:2347 Furthermore the freeze-resistant cells remained viable after freezing and thawing but a modification of protein secondary structure was detected by SR-FTIR analysis. 26212688 8 56 used used 1216:1219 arg2 analysis 1203:1210 Principal component analysis 1183:1210 Principal component analysis 1183:1210 Principal component analysis was used to evaluate changes in cell composition, with particular focus on lipids, proteins and polysaccharides. 26212688 10 57 from diversity 1789:1797 arg1 medium 1837:1842 the growth medium 1826:1842 the growth medium 1826:1842 Moreover, SR-FTIR microspectroscopy made it possible to reveal cell heterogeneity within the cluster of resistant cells, which was ascribed to the diversity of potential substrates in the growth medium. 26212688 14 58 theme potential 2380:2388 arg1 application 2390:2400 the potential application 2376:2400 the potential application of bimodal analysis 2376:2420 These results highlighted the potential application of bimodal analysis by SR-FTIR and fluorescence microscopy to increase our knowledge about mechanisms related to cell damage. 26212688 6 59 theme Infrared 752:759 arg1 spectra 761:767 Infrared spectra 752:767 Infrared spectra of individual bacteria produced by applying different fermentation and freezing conditions 752:858 Infrared spectra of individual bacteria produced by applying different fermentation and freezing conditions were acquired using synchrotron radiation-based Fourier-transform infrared (SR-FTIR) microspectroscopy to achieve sub-cellular spatial resolution. 26212688 10 60 theme growth 1830:1835 arg1 medium 1837:1842 the growth medium 1826:1842 the growth medium 1826:1842 Moreover, SR-FTIR microspectroscopy made it possible to reveal cell heterogeneity within the cluster of resistant cells, which was ascribed to the diversity of potential substrates in the growth medium. 26212688 9 61 theme α-helix 1500:1506 arg1 structure 1518:1526 an α-helix secondary structure 1497:1526 an α-helix secondary structure 1497:1526 SR-FTIR results indicated that before freezing, freeze-resistant cells grown in a rich medium presented a high content of CH3 groups from lipid chains, of cell proteins in an α-helix secondary structure and of charged polymers such as teichoic and lipoteichoic acids that constitute the Gram-positive bacterial wall. 26212688 12 62 theme membrane 2155:2162 arg1 rigidification 2121:2134 a rigidification 2119:2134 particular a rigidification of the cytoplasmic membrane following freezing 2108:2181 These damages leading to cell death were ascribed to biochemical modification of cell membrane phospholipids, in particular a rigidification of the cytoplasmic membrane following freezing. 26212688 13 63 theme structure 2306:2314 arg1 modification 2272:2283 a modification 2270:2283 a modification of protein secondary structure 2270:2314 Furthermore the freeze-resistant cells remained viable after freezing and thawing but a modification of protein secondary structure was detected by SR-FTIR analysis. 26212688 6 64 theme spatial 987:993 arg1 resolution 995:1004 sub-cellular spatial resolution 974:1004 sub-cellular spatial resolution 974:1004 Infrared spectra of individual bacteria produced by applying different fermentation and freezing conditions were acquired using synchrotron radiation-based Fourier-transform infrared (SR-FTIR) microspectroscopy to achieve sub-cellular spatial resolution. 26212688 1 65 theme cells 181:185 arg1 types 172:176 different types 162:176 different types of cells 162:185 Freezing is widely used for preserving different types of cells. 26212688 9 66 theme polymers 1543:1550 arg1 chains 1469:1474 lipid chains 1463:1474 lipid chains 1463:1474 SR-FTIR results indicated that before freezing, freeze-resistant cells grown in a rich medium presented a high content of CH3 groups from lipid chains, of cell proteins in an α-helix secondary structure and of charged polymers such as teichoic and lipoteichoic acids that constitute the Gram-positive bacterial wall. 26212688 12 67 theme membrane 2081:2088 arg1 phospholipids 2090:2102 cell membrane phospholipids 2076:2102 cell membrane phospholipids 2076:2102 These damages leading to cell death were ascribed to biochemical modification of cell membrane phospholipids, in particular a rigidification of the cytoplasmic membrane following freezing. 26212688 1 68 used used 142:145 arg2 Freezing 123:130 Freezing 123:130 Freezing 123:130 Freezing is widely used for preserving different types of cells. 26212688 10 69 theme cell 1705:1708 arg1 heterogeneity 1710:1722 cell heterogeneity 1705:1722 cell heterogeneity 1705:1722 Moreover, SR-FTIR microspectroscopy made it possible to reveal cell heterogeneity within the cluster of resistant cells, which was ascribed to the diversity of potential substrates in the growth medium. 26212688 11 70 theme viability 1922:1930 arg1 losses 1884:1889 losses 1884:1889 losses of membrane integrity and cell viability 1884:1930 Freezing and thawing processes induced losses of membrane integrity and cell viability in more than 90% of the freeze-sensitive bacterial population. 26212688 6 71 theme different 813:821 arg1 fermentation 823:834 different fermentation and freezing conditions 813:858 fermentation 823:834 Infrared spectra of individual bacteria produced by applying different fermentation and freezing conditions were acquired using synchrotron radiation-based Fourier-transform infrared (SR-FTIR) microspectroscopy to achieve sub-cellular spatial resolution. 26212688 10 72 theme resistant 1746:1754 arg1 cells 1756:1760 resistant cells 1746:1760 resistant cells 1746:1760 Moreover, SR-FTIR microspectroscopy made it possible to reveal cell heterogeneity within the cluster of resistant cells, which was ascribed to the diversity of potential substrates in the growth medium. 26212688 11 73 theme freeze-sensitive 1956:1971 arg1 population 1983:1992 the freeze-sensitive bacterial population 1952:1992 the freeze-sensitive bacterial population 1952:1992 Freezing and thawing processes induced losses of membrane integrity and cell viability in more than 90% of the freeze-sensitive bacterial population. 26212688 5 74 theme cryotolerance 737:749 arg1 biomarkers 723:732 cellular biomarkers 714:732 cellular biomarkers of cryotolerance 714:749 Our objective was to investigate the biochemical and physiological changes in a LAB model at the cell scale following fermentation and freezing in order to identify cellular biomarkers of cryotolerance. 26212688 12 75 theme biochemical 2048:2058 arg1 modification 2060:2071 biochemical modification 2048:2071 biochemical modification of cell membrane phospholipids 2048:2102 These damages leading to cell death were ascribed to biochemical modification of cell membrane phospholipids, in particular a rigidification of the cytoplasmic membrane following freezing. 26212688 4 76 theme bacterial 477:485 arg1 populations 487:497 homogeneous bacterial populations 465:497 homogeneous bacterial populations 465:497 Producing homogeneous bacterial populations with high cryotolerance remains a real challenge. 26212688 7 77 theme cell 1158:1161 arg1 biochemistry 1109:1120 biochemistry 1109:1120 biochemistry 1109:1120 Fluorescent microscopy was concomitantly assessed, thus making possible to simultaneously analyse the biochemistry and physiological state of a single cell for the first time. 26212688 7 77 theme cell 1158:1161 arg1 state 1140:1144 physiological state 1126:1144 physiological state 1126:1144 Fluorescent microscopy was concomitantly assessed, thus making possible to simultaneously analyse the biochemistry and physiological state of a single cell for the first time. 26212688 5 78 from changes 616:622 arg1 model 633:637 a LAB model 627:637 a LAB model 627:637 Our objective was to investigate the biochemical and physiological changes in a LAB model at the cell scale following fermentation and freezing in order to identify cellular biomarkers of cryotolerance. 26212688 13 79 theme secondary 2296:2304 arg1 structure 2306:2314 protein secondary structure 2288:2314 protein secondary structure 2288:2314 Furthermore the freeze-resistant cells remained viable after freezing and thawing but a modification of protein secondary structure was detected by SR-FTIR analysis. 26212688 8 80 from focus 1278:1282 arg1 proteins 1295:1302 proteins 1295:1302 proteins 1295:1302 Principal component analysis was used to evaluate changes in cell composition, with particular focus on lipids, proteins and polysaccharides. 26212688 8 80 from focus 1278:1282 arg1 lipids 1287:1292 lipids 1287:1292 lipids 1287:1292 Principal component analysis was used to evaluate changes in cell composition, with particular focus on lipids, proteins and polysaccharides. 26212688 8 80 from focus 1278:1282 arg1 polysaccharides 1308:1322 polysaccharides 1308:1322 polysaccharides 1308:1322 Principal component analysis was used to evaluate changes in cell composition, with particular focus on lipids, proteins and polysaccharides. 26212688 14 81 theme cell 2515:2518 arg1 damage 2520:2525 cell damage 2515:2525 cell damage 2515:2525 These results highlighted the potential application of bimodal analysis by SR-FTIR and fluorescence microscopy to increase our knowledge about mechanisms related to cell damage. 26212688 5 82 theme biochemical 586:596 arg1 changes 616:622 the biochemical and physiological changes 582:622 the biochemical and physiological changes in a LAB model at the cell scale 582:655 Our objective was to investigate the biochemical and physiological changes in a LAB model at the cell scale following fermentation and freezing in order to identify cellular biomarkers of cryotolerance. 26212688 9 83 theme freeze-resistant 1373:1388 arg1 cells 1390:1394 freeze-resistant cells 1373:1394 freeze-resistant cells grown in a rich medium 1373:1417 SR-FTIR results indicated that before freezing, freeze-resistant cells grown in a rich medium presented a high content of CH3 groups from lipid chains, of cell proteins in an α-helix secondary structure and of charged polymers such as teichoic and lipoteichoic acids that constitute the Gram-positive bacterial wall. 26212688 7 84 theme physiological 1126:1138 arg1 state 1140:1144 physiological state 1126:1144 physiological state 1126:1144 Fluorescent microscopy was concomitantly assessed, thus making possible to simultaneously analyse the biochemistry and physiological state of a single cell for the first time. 26212688 14 85 theme related 2504:2510 arg1 mechanisms 2493:2502 mechanisms 2493:2502 mechanisms related to cell damage 2493:2525 These results highlighted the potential application of bimodal analysis by SR-FTIR and fluorescence microscopy to increase our knowledge about mechanisms related to cell damage. 26212688 10 86 theme potential 1802:1810 arg1 substrates 1812:1821 potential substrates 1802:1821 potential substrates 1802:1821 Moreover, SR-FTIR microspectroscopy made it possible to reveal cell heterogeneity within the cluster of resistant cells, which was ascribed to the diversity of potential substrates in the growth medium. 26212688 0 87 theme synchrotron 71:81 arg1 infrared 83:90 combined synchrotron infrared 62:90 combined synchrotron infrared 62:90 Understanding the cryotolerance of lactic acid bacteria using combined synchrotron infrared and fluorescence microscopies. 26212688 9 88 theme Gram-positive 1612:1624 arg1 wall 1636:1639 the Gram-positive bacterial wall 1608:1639 the Gram-positive bacterial wall 1608:1639 SR-FTIR results indicated that before freezing, freeze-resistant cells grown in a rich medium presented a high content of CH3 groups from lipid chains, of cell proteins in an α-helix secondary structure and of charged polymers such as teichoic and lipoteichoic acids that constitute the Gram-positive bacterial wall. 26212688 2 89 dep food 277:280 arg1 probiotic 283:291 probiotic 283:291 probiotic 283:291 Frozen concentrates of lactic acid bacteria (LAB) are extensively used for manufacturing food, probiotic products and for green chemistry and medical applications. 26212688 8 90 from changes 1233:1239 arg1 composition 1249:1259 cell composition 1244:1259 cell composition 1244:1259 Principal component analysis was used to evaluate changes in cell composition, with particular focus on lipids, proteins and polysaccharides. 26212688 11 91 theme membrane 1894:1901 arg1 integrity 1903:1911 membrane integrity 1894:1911 membrane integrity 1894:1911 Freezing and thawing processes induced losses of membrane integrity and cell viability in more than 90% of the freeze-sensitive bacterial population. 26212688 5 92 theme LAB 629:631 arg1 model 633:637 a LAB model 627:637 a LAB model 627:637 Our objective was to investigate the biochemical and physiological changes in a LAB model at the cell scale following fermentation and freezing in order to identify cellular biomarkers of cryotolerance. 26212688 3 93 theme freezing 365:372 arg1 processes 386:394 the freezing and thawing processes 361:394 the freezing and thawing processes 361:394 However, the freezing and thawing processes cause cell injuries that result in significant cell death. 26212688 14 94 theme fluorescence 2437:2448 arg1 microscopy 2450:2459 fluorescence microscopy 2437:2459 fluorescence microscopy 2437:2459 These results highlighted the potential application of bimodal analysis by SR-FTIR and fluorescence microscopy to increase our knowledge about mechanisms related to cell damage. 26212688 12 95 theme cell 2020:2023 arg1 death 2025:2029 cell death 2020:2029 cell death 2020:2029 These damages leading to cell death were ascribed to biochemical modification of cell membrane phospholipids, in particular a rigidification of the cytoplasmic membrane following freezing. 26212688 5 96 theme physiological 602:614 arg1 changes 616:622 the biochemical and physiological changes 582:622 the biochemical and physiological changes in a LAB model at the cell scale 582:655 Our objective was to investigate the biochemical and physiological changes in a LAB model at the cell scale following fermentation and freezing in order to identify cellular biomarkers of cryotolerance. 26212688 3 97 theme significant 431:441 arg1 death 448:452 significant cell death 431:452 significant cell death 431:452 However, the freezing and thawing processes cause cell injuries that result in significant cell death. 26212688 9 98 theme CH3 1447:1449 arg1 groups 1451:1456 CH3 groups 1447:1456 CH3 groups 1447:1456 SR-FTIR results indicated that before freezing, freeze-resistant cells grown in a rich medium presented a high content of CH3 groups from lipid chains, of cell proteins in an α-helix secondary structure and of charged polymers such as teichoic and lipoteichoic acids that constitute the Gram-positive bacterial wall. 26212688 8 99 theme component 1193:1201 arg1 analysis 1203:1210 Principal component analysis 1183:1210 Principal component analysis 1183:1210 Principal component analysis was used to evaluate changes in cell composition, with particular focus on lipids, proteins and polysaccharides. 26212688 3 100 theme thawing 378:384 arg1 processes 386:394 the freezing and thawing processes 361:394 the freezing and thawing processes 361:394 However, the freezing and thawing processes cause cell injuries that result in significant cell death. 26212688 12 101 theme cytoplasmic 2143:2153 arg1 membrane 2155:2162 the cytoplasmic membrane 2139:2162 the cytoplasmic membrane 2139:2162 These damages leading to cell death were ascribed to biochemical modification of cell membrane phospholipids, in particular a rigidification of the cytoplasmic membrane following freezing. 26212688 14 102 theme analysis 2413:2420 arg1 application 2390:2400 the potential application 2376:2400 the potential application of bimodal analysis 2376:2420 These results highlighted the potential application of bimodal analysis by SR-FTIR and fluorescence microscopy to increase our knowledge about mechanisms related to cell damage. 26212688 0 103 theme acid 42:45 arg1 bacteria 47:54 lactic acid bacteria 35:54 lactic acid bacteria using combined synchrotron infrared and fluorescence microscopies 35:120 Understanding the cryotolerance of lactic acid bacteria using combined synchrotron infrared and fluorescence microscopies. 26212688 12 104 dep particular 2108:2117 arg1 rigidification 2121:2134 a rigidification 2119:2134 particular a rigidification of the cytoplasmic membrane following freezing 2108:2181 These damages leading to cell death were ascribed to biochemical modification of cell membrane phospholipids, in particular a rigidification of the cytoplasmic membrane following freezing. 26212688 2 105 theme bacteria 223:230 arg1 concentrates 195:206 Frozen concentrates 188:206 Frozen concentrates of lactic acid bacteria (LAB) 188:236 Frozen concentrates of lactic acid bacteria (LAB) are extensively used for manufacturing food, probiotic products and for green chemistry and medical applications. 26212688 10 106 theme substrates 1812:1821 arg1 diversity 1789:1797 the diversity 1785:1797 the diversity of potential substrates in the growth medium 1785:1842 Moreover, SR-FTIR microspectroscopy made it possible to reveal cell heterogeneity within the cluster of resistant cells, which was ascribed to the diversity of potential substrates in the growth medium. 26212688 7 107 theme Fluorescent 1007:1017 arg1 microscopy 1019:1028 Fluorescent microscopy 1007:1028 Fluorescent microscopy 1007:1028 Fluorescent microscopy was concomitantly assessed, thus making possible to simultaneously analyse the biochemistry and physiological state of a single cell for the first time. 26212688 6 108 theme Fourier-transform 908:924 arg1 microspectroscopy 945:961 synchrotron radiation-based Fourier-transform infrared (SR-FTIR) microspectroscopy 880:961 synchrotron radiation-based Fourier-transform infrared (SR-FTIR) microspectroscopy 880:961 Infrared spectra of individual bacteria produced by applying different fermentation and freezing conditions were acquired using synchrotron radiation-based Fourier-transform infrared (SR-FTIR) microspectroscopy to achieve sub-cellular spatial resolution. 26212688 2 109 theme lactic 211:216 arg1 LAB 233:235 LAB 233:235 LAB 233:235 Frozen concentrates of lactic acid bacteria (LAB) are extensively used for manufacturing food, probiotic products and for green chemistry and medical applications. 26212688 2 109 theme lactic 211:216 arg1 bacteria 223:230 lactic acid bacteria 211:230 lactic acid bacteria (LAB) 211:236 Frozen concentrates of lactic acid bacteria (LAB) are extensively used for manufacturing food, probiotic products and for green chemistry and medical applications. 26212688 6 110 theme individual 772:781 arg1 bacteria 783:790 individual bacteria 772:790 individual bacteria produced by applying different fermentation and freezing conditions 772:858 Infrared spectra of individual bacteria produced by applying different fermentation and freezing conditions were acquired using synchrotron radiation-based Fourier-transform infrared (SR-FTIR) microspectroscopy to achieve sub-cellular spatial resolution. 26212688 9 111 theme proteins 1485:1492 arg1 chains 1469:1474 lipid chains 1463:1474 lipid chains 1463:1474 SR-FTIR results indicated that before freezing, freeze-resistant cells grown in a rich medium presented a high content of CH3 groups from lipid chains, of cell proteins in an α-helix secondary structure and of charged polymers such as teichoic and lipoteichoic acids that constitute the Gram-positive bacterial wall. 26212688 8 112 theme cell 1244:1247 arg1 composition 1249:1259 cell composition 1244:1259 cell composition 1244:1259 Principal component analysis was used to evaluate changes in cell composition, with particular focus on lipids, proteins and polysaccharides. 26212688 6 113 theme synchrotron 880:890 arg1 microspectroscopy 945:961 synchrotron radiation-based Fourier-transform infrared (SR-FTIR) microspectroscopy 880:961 synchrotron radiation-based Fourier-transform infrared (SR-FTIR) microspectroscopy 880:961 Infrared spectra of individual bacteria produced by applying different fermentation and freezing conditions were acquired using synchrotron radiation-based Fourier-transform infrared (SR-FTIR) microspectroscopy to achieve sub-cellular spatial resolution. 26212688 10 114 theme SR-FTIR 1652:1658 arg1 microspectroscopy 1660:1676 SR-FTIR microspectroscopy 1652:1676 SR-FTIR microspectroscopy 1652:1676 Moreover, SR-FTIR microspectroscopy made it possible to reveal cell heterogeneity within the cluster of resistant cells, which was ascribed to the diversity of potential substrates in the growth medium. 24999116 10 0 theme PAC 1585:1587 arg1 addition 1590:1597 powdered activated carbon (PAC) addition 1558:1597 powdered activated carbon (PAC) addition used for remediation 1558:1618 A similar experiment introducing powdered activated carbon (PAC) addition used for remediation resulted in either no or less significant changes in the above mentioned quantities, signifying its potential as a mitigation strategy. 24999116 4 1 theme improved 522:529 arg1 insight 531:537 improved insight 522:537 improved insight into the impact of fouling 522:564 Therefore, improved insight into the impact of fouling is crucial towards increased membrane performance. 24999116 6 2 theme potential 1081:1089 arg1 mechanism 1101:1109 the potential governing mechanism 1077:1109 its impact as well as the potential governing mechanism 1055:1109 Several key sludge parameters (soluble microbial products, sludge-bound extracellular polymeric substances, supramicron particle size distributions (PSD), submicron particle concentrations) were intensively monitored prior to, during, and after a disturbance to investigate its impact as well as the potential governing mechanism. 24999116 1 3 theme Membrane 144:151 arg1 technology 188:197 a well-established technology 169:197 a well-established technology for wastewater treatment 169:222 Membrane bioreactors are a well-established technology for wastewater treatment. 24999116 1 3 theme Membrane 144:151 arg1 bioreactors 153:163 Membrane bioreactors 144:163 Membrane bioreactors 144:163 Membrane bioreactors are a well-established technology for wastewater treatment. 24999116 0 4 theme properties 57:66 arg1 fouling 78:84 membrane fouling 69:84 membrane fouling 69:84 Salt stress in a membrane bioreactor: dynamics of sludge properties, membrane fouling and remediation through powdered activated carbon dosing. 24999116 0 4 theme properties 57:66 arg1 remediation 90:100 remediation 90:100 remediation 90:100 Salt stress in a membrane bioreactor: dynamics of sludge properties, membrane fouling and remediation through powdered activated carbon dosing. 24999116 0 4 theme properties 57:66 arg1 dynamics 38:45 dynamics 38:45 dynamics of sludge properties 38:66 Salt stress in a membrane bioreactor: dynamics of sludge properties, membrane fouling and remediation through powdered activated carbon dosing. 24999116 0 5 from stress 5:10 arg1 bioreactor 26:35 a membrane bioreactor 15:35 a membrane bioreactor 15:35 Salt stress in a membrane bioreactor: dynamics of sludge properties, membrane fouling and remediation through powdered activated carbon dosing. 24999116 6 6 theme polymeric 867:875 arg1 substances 877:886 sludge-bound extracellular polymeric substances 840:886 sludge-bound extracellular polymeric substances 840:886 Several key sludge parameters (soluble microbial products, sludge-bound extracellular polymeric substances, supramicron particle size distributions (PSD), submicron particle concentrations) were intensively monitored prior to, during, and after a disturbance to investigate its impact as well as the potential governing mechanism. 24999116 6 6 theme polymeric 867:875 arg1 products 830:837 soluble microbial products 812:837 soluble microbial products 812:837 Several key sludge parameters (soluble microbial products, sludge-bound extracellular polymeric substances, supramicron particle size distributions (PSD), submicron particle concentrations) were intensively monitored prior to, during, and after a disturbance to investigate its impact as well as the potential governing mechanism. 24999116 6 7 dep parameters 800:809 arg1 distributions 915:927 supramicron particle size distributions 889:927 supramicron particle size distributions (PSD) 889:933 Several key sludge parameters (soluble microbial products, sludge-bound extracellular polymeric substances, supramicron particle size distributions (PSD), submicron particle concentrations) were intensively monitored prior to, during, and after a disturbance to investigate its impact as well as the potential governing mechanism. 24999116 6 7 dep parameters 800:809 arg1 substances 877:886 sludge-bound extracellular polymeric substances 840:886 sludge-bound extracellular polymeric substances 840:886 Several key sludge parameters (soluble microbial products, sludge-bound extracellular polymeric substances, supramicron particle size distributions (PSD), submicron particle concentrations) were intensively monitored prior to, during, and after a disturbance to investigate its impact as well as the potential governing mechanism. 24999116 6 7 dep parameters 800:809 arg1 products 830:837 soluble microbial products 812:837 soluble microbial products 812:837 Several key sludge parameters (soluble microbial products, sludge-bound extracellular polymeric substances, supramicron particle size distributions (PSD), submicron particle concentrations) were intensively monitored prior to, during, and after a disturbance to investigate its impact as well as the potential governing mechanism. 24999116 6 7 dep parameters 800:809 arg1 concentrations 955:968 submicron particle concentrations 936:968 submicron particle concentrations 936:968 Several key sludge parameters (soluble microbial products, sludge-bound extracellular polymeric substances, supramicron particle size distributions (PSD), submicron particle concentrations) were intensively monitored prior to, during, and after a disturbance to investigate its impact as well as the potential governing mechanism. 24999116 5 8 theme lab-scale 749:757 arg1 bioreactors 768:778 two parallel lab-scale membrane bioreactors 736:778 two parallel lab-scale membrane bioreactors 736:778 In this work, the disturbance of a salt shock was investigated with respect to sludge composition and filterability in two parallel lab-scale membrane bioreactors. 24999116 6 9 theme extracellular 853:865 arg1 substances 877:886 sludge-bound extracellular polymeric substances 840:886 sludge-bound extracellular polymeric substances 840:886 Several key sludge parameters (soluble microbial products, sludge-bound extracellular polymeric substances, supramicron particle size distributions (PSD), submicron particle concentrations) were intensively monitored prior to, during, and after a disturbance to investigate its impact as well as the potential governing mechanism. 24999116 6 9 theme extracellular 853:865 arg1 products 830:837 soluble microbial products 812:837 soluble microbial products 812:837 Several key sludge parameters (soluble microbial products, sludge-bound extracellular polymeric substances, supramicron particle size distributions (PSD), submicron particle concentrations) were intensively monitored prior to, during, and after a disturbance to investigate its impact as well as the potential governing mechanism. 24999116 5 10 from filterability 719:731 arg1 bioreactors 768:778 two parallel lab-scale membrane bioreactors 736:778 two parallel lab-scale membrane bioreactors 736:778 In this work, the disturbance of a salt shock was investigated with respect to sludge composition and filterability in two parallel lab-scale membrane bioreactors. 24999116 0 11 theme membrane 69:76 arg1 fouling 78:84 membrane fouling 69:84 membrane fouling 69:84 Salt stress in a membrane bioreactor: dynamics of sludge properties, membrane fouling and remediation through powdered activated carbon dosing. 24999116 0 11 theme membrane 69:76 arg1 dynamics 38:45 dynamics 38:45 dynamics of sludge properties 38:66 Salt stress in a membrane bioreactor: dynamics of sludge properties, membrane fouling and remediation through powdered activated carbon dosing. 24999116 6 12 theme particle 946:953 arg1 products 830:837 soluble microbial products 812:837 soluble microbial products 812:837 Several key sludge parameters (soluble microbial products, sludge-bound extracellular polymeric substances, supramicron particle size distributions (PSD), submicron particle concentrations) were intensively monitored prior to, during, and after a disturbance to investigate its impact as well as the potential governing mechanism. 24999116 6 12 theme particle 946:953 arg1 concentrations 955:968 submicron particle concentrations 936:968 submicron particle concentrations 936:968 Several key sludge parameters (soluble microbial products, sludge-bound extracellular polymeric substances, supramicron particle size distributions (PSD), submicron particle concentrations) were intensively monitored prior to, during, and after a disturbance to investigate its impact as well as the potential governing mechanism. 24999116 6 13 theme sludge-bound 840:851 arg1 substances 877:886 sludge-bound extracellular polymeric substances 840:886 sludge-bound extracellular polymeric substances 840:886 Several key sludge parameters (soluble microbial products, sludge-bound extracellular polymeric substances, supramicron particle size distributions (PSD), submicron particle concentrations) were intensively monitored prior to, during, and after a disturbance to investigate its impact as well as the potential governing mechanism. 24999116 6 13 theme sludge-bound 840:851 arg1 products 830:837 soluble microbial products 812:837 soluble microbial products 812:837 Several key sludge parameters (soluble microbial products, sludge-bound extracellular polymeric substances, supramicron particle size distributions (PSD), submicron particle concentrations) were intensively monitored prior to, during, and after a disturbance to investigate its impact as well as the potential governing mechanism. 24999116 10 14 theme similar 1527:1533 arg1 experiment 1535:1544 A similar experiment 1525:1544 A similar experiment introducing powdered activated carbon (PAC) addition used for remediation 1525:1618 A similar experiment introducing powdered activated carbon (PAC) addition used for remediation resulted in either no or less significant changes in the above mentioned quantities, signifying its potential as a mitigation strategy. 24999116 6 15 theme submicron 936:944 arg1 products 830:837 soluble microbial products 812:837 soluble microbial products 812:837 Several key sludge parameters (soluble microbial products, sludge-bound extracellular polymeric substances, supramicron particle size distributions (PSD), submicron particle concentrations) were intensively monitored prior to, during, and after a disturbance to investigate its impact as well as the potential governing mechanism. 24999116 6 15 theme submicron 936:944 arg1 concentrations 955:968 submicron particle concentrations 936:968 submicron particle concentrations 936:968 Several key sludge parameters (soluble microbial products, sludge-bound extracellular polymeric substances, supramicron particle size distributions (PSD), submicron particle concentrations) were intensively monitored prior to, during, and after a disturbance to investigate its impact as well as the potential governing mechanism. 24999116 8 16 theme submicron 1275:1283 arg1 particles 1285:1293 submicron particles 1275:1293 submicron particles 1275:1293 Following a certain delay, an increase in submicron particles, supernatant proteins, and polysaccharides was observed as well as an increase in the irreversible membrane fouling rate. 24999116 3 17 theme system 490:495 arg1 disturbances 497:508 system disturbances 490:508 system disturbances 490:508 This fouling propensity of the activated sludge is closely related to system disturbances. 24999116 1 18 theme well-established 171:186 arg1 technology 188:197 a well-established technology 169:197 a well-established technology for wastewater treatment 169:222 Membrane bioreactors are a well-established technology for wastewater treatment. 24999116 1 18 theme well-established 171:186 arg1 bioreactors 153:163 Membrane bioreactors 144:163 Membrane bioreactors 144:163 Membrane bioreactors are a well-established technology for wastewater treatment. 24999116 3 19 theme sludge 461:466 arg1 propensity 433:442 This fouling propensity 420:442 This fouling propensity of the activated sludge 420:466 This fouling propensity of the activated sludge is closely related to system disturbances. 24999116 7 20 theme floc 1183:1186 arg1 sizes 1188:1192 smaller floc sizes 1175:1192 smaller floc sizes 1175:1192 Upon salt addition, the supramicron PSD immediately shifted to smaller floc sizes, and the total fouling rate increased. 24999116 7 21 theme supramicron 1136:1146 arg1 PSD 1148:1150 the supramicron PSD 1132:1150 the supramicron PSD 1132:1150 Upon salt addition, the supramicron PSD immediately shifted to smaller floc sizes, and the total fouling rate increased. 24999116 2 22 theme membrane 276:283 arg1 fouling 285:291 membrane fouling 276:291 membrane fouling 276:291 However, their efficiency is adversely impacted by membrane fouling, primarily inciting very conservative operations of installations that makes them less appealing from an economic perspective. 24999116 9 23 theme simultaneous 1468:1479 arg1 decrease 1481:1488 a simultaneous decrease 1466:1488 a simultaneous decrease in the above mentioned quantities 1466:1522 Recovery from the disturbance was evidenced with a simultaneous decrease in the above mentioned quantities. 24999116 7 24 theme total 1203:1207 arg1 rate 1217:1220 the total fouling rate 1199:1220 the total fouling rate 1199:1220 Upon salt addition, the supramicron PSD immediately shifted to smaller floc sizes, and the total fouling rate increased. 24999116 10 25 from changes 1662:1668 arg1 quantities 1693:1702 the above mentioned quantities 1673:1702 the above mentioned quantities 1673:1702 A similar experiment introducing powdered activated carbon (PAC) addition used for remediation resulted in either no or less significant changes in the above mentioned quantities, signifying its potential as a mitigation strategy. 24999116 5 26 theme salt 652:655 arg1 shock 657:661 a salt shock 650:661 a salt shock 650:661 In this work, the disturbance of a salt shock was investigated with respect to sludge composition and filterability in two parallel lab-scale membrane bioreactors. 24999116 6 27 theme microbial 820:828 arg1 distributions 915:927 supramicron particle size distributions 889:927 supramicron particle size distributions (PSD) 889:933 Several key sludge parameters (soluble microbial products, sludge-bound extracellular polymeric substances, supramicron particle size distributions (PSD), submicron particle concentrations) were intensively monitored prior to, during, and after a disturbance to investigate its impact as well as the potential governing mechanism. 24999116 6 27 theme microbial 820:828 arg1 substances 877:886 sludge-bound extracellular polymeric substances 840:886 sludge-bound extracellular polymeric substances 840:886 Several key sludge parameters (soluble microbial products, sludge-bound extracellular polymeric substances, supramicron particle size distributions (PSD), submicron particle concentrations) were intensively monitored prior to, during, and after a disturbance to investigate its impact as well as the potential governing mechanism. 24999116 6 27 theme microbial 820:828 arg1 products 830:837 soluble microbial products 812:837 soluble microbial products 812:837 Several key sludge parameters (soluble microbial products, sludge-bound extracellular polymeric substances, supramicron particle size distributions (PSD), submicron particle concentrations) were intensively monitored prior to, during, and after a disturbance to investigate its impact as well as the potential governing mechanism. 24999116 6 27 theme microbial 820:828 arg1 concentrations 955:968 submicron particle concentrations 936:968 submicron particle concentrations 936:968 Several key sludge parameters (soluble microbial products, sludge-bound extracellular polymeric substances, supramicron particle size distributions (PSD), submicron particle concentrations) were intensively monitored prior to, during, and after a disturbance to investigate its impact as well as the potential governing mechanism. 24999116 8 28 theme membrane 1394:1401 arg1 rate 1411:1414 the irreversible membrane fouling rate 1377:1414 the irreversible membrane fouling rate 1377:1414 Following a certain delay, an increase in submicron particles, supernatant proteins, and polysaccharides was observed as well as an increase in the irreversible membrane fouling rate. 24999116 10 29 theme activated 1567:1575 arg1 addition 1590:1597 powdered activated carbon (PAC) addition 1558:1597 powdered activated carbon (PAC) addition used for remediation 1558:1618 A similar experiment introducing powdered activated carbon (PAC) addition used for remediation resulted in either no or less significant changes in the above mentioned quantities, signifying its potential as a mitigation strategy. 24999116 2 30 theme economic 398:405 arg1 perspective 407:417 an economic perspective 395:417 an economic perspective 395:417 However, their efficiency is adversely impacted by membrane fouling, primarily inciting very conservative operations of installations that makes them less appealing from an economic perspective. 24999116 0 31 theme Salt 0:3 arg1 stress 5:10 Salt stress 0:10 Salt stress in a membrane bioreactor: dynamics of sludge properties, membrane fouling and remediation through powdered activated carbon dosing. 0:142 Salt stress in a membrane bioreactor: dynamics of sludge properties, membrane fouling and remediation through powdered activated carbon dosing. 24999116 5 32 theme shock 657:661 arg1 disturbance 635:645 the disturbance 631:645 the disturbance of a salt shock 631:661 In this work, the disturbance of a salt shock was investigated with respect to sludge composition and filterability in two parallel lab-scale membrane bioreactors. 24999116 6 33 theme soluble 812:818 arg1 distributions 915:927 supramicron particle size distributions 889:927 supramicron particle size distributions (PSD) 889:933 Several key sludge parameters (soluble microbial products, sludge-bound extracellular polymeric substances, supramicron particle size distributions (PSD), submicron particle concentrations) were intensively monitored prior to, during, and after a disturbance to investigate its impact as well as the potential governing mechanism. 24999116 6 33 theme soluble 812:818 arg1 substances 877:886 sludge-bound extracellular polymeric substances 840:886 sludge-bound extracellular polymeric substances 840:886 Several key sludge parameters (soluble microbial products, sludge-bound extracellular polymeric substances, supramicron particle size distributions (PSD), submicron particle concentrations) were intensively monitored prior to, during, and after a disturbance to investigate its impact as well as the potential governing mechanism. 24999116 6 33 theme soluble 812:818 arg1 products 830:837 soluble microbial products 812:837 soluble microbial products 812:837 Several key sludge parameters (soluble microbial products, sludge-bound extracellular polymeric substances, supramicron particle size distributions (PSD), submicron particle concentrations) were intensively monitored prior to, during, and after a disturbance to investigate its impact as well as the potential governing mechanism. 24999116 6 33 theme soluble 812:818 arg1 concentrations 955:968 submicron particle concentrations 936:968 submicron particle concentrations 936:968 Several key sludge parameters (soluble microbial products, sludge-bound extracellular polymeric substances, supramicron particle size distributions (PSD), submicron particle concentrations) were intensively monitored prior to, during, and after a disturbance to investigate its impact as well as the potential governing mechanism. 24999116 2 34 theme conservative 318:329 arg1 operations 331:340 very conservative operations 313:340 very conservative operations of installations that makes them less appealing from an economic perspective 313:417 However, their efficiency is adversely impacted by membrane fouling, primarily inciting very conservative operations of installations that makes them less appealing from an economic perspective. 24999116 3 35 theme activated 451:459 arg1 sludge 461:466 the activated sludge 447:466 the activated sludge 447:466 This fouling propensity of the activated sludge is closely related to system disturbances. 24999116 0 36 theme powdered 110:117 arg1 dosing 136:141 powdered activated carbon dosing 110:141 powdered activated carbon dosing 110:141 Salt stress in a membrane bioreactor: dynamics of sludge properties, membrane fouling and remediation through powdered activated carbon dosing. 24999116 10 37 theme above 1677:1681 arg1 quantities 1693:1702 the above mentioned quantities 1673:1702 the above mentioned quantities 1673:1702 A similar experiment introducing powdered activated carbon (PAC) addition used for remediation resulted in either no or less significant changes in the above mentioned quantities, signifying its potential as a mitigation strategy. 24999116 9 38 theme above 1497:1501 arg1 quantities 1513:1522 the above mentioned quantities 1493:1522 the above mentioned quantities 1493:1522 Recovery from the disturbance was evidenced with a simultaneous decrease in the above mentioned quantities. 24999116 6 39 theme governing 1091:1099 arg1 mechanism 1101:1109 the potential governing mechanism 1077:1109 its impact as well as the potential governing mechanism 1055:1109 Several key sludge parameters (soluble microbial products, sludge-bound extracellular polymeric substances, supramicron particle size distributions (PSD), submicron particle concentrations) were intensively monitored prior to, during, and after a disturbance to investigate its impact as well as the potential governing mechanism. 24999116 8 40 theme irreversible 1381:1392 arg1 rate 1411:1414 the irreversible membrane fouling rate 1377:1414 the irreversible membrane fouling rate 1377:1414 Following a certain delay, an increase in submicron particles, supernatant proteins, and polysaccharides was observed as well as an increase in the irreversible membrane fouling rate. 24999116 4 41 theme membrane 595:602 arg1 performance 604:614 increased membrane performance 585:614 increased membrane performance 585:614 Therefore, improved insight into the impact of fouling is crucial towards increased membrane performance. 24999116 7 42 theme salt 1117:1120 arg1 addition 1122:1129 salt addition 1117:1129 salt addition 1117:1129 Upon salt addition, the supramicron PSD immediately shifted to smaller floc sizes, and the total fouling rate increased. 24999116 6 43 dep prior 998:1002 arg1 to 1004:1005 to 1004:1005 to 1004:1005 Several key sludge parameters (soluble microbial products, sludge-bound extracellular polymeric substances, supramicron particle size distributions (PSD), submicron particle concentrations) were intensively monitored prior to, during, and after a disturbance to investigate its impact as well as the potential governing mechanism. 24999116 8 44 theme fouling 1403:1409 arg1 rate 1411:1414 the irreversible membrane fouling rate 1377:1414 the irreversible membrane fouling rate 1377:1414 Following a certain delay, an increase in submicron particles, supernatant proteins, and polysaccharides was observed as well as an increase in the irreversible membrane fouling rate. 24999116 9 45 from disturbance 1435:1445 arg1 Recovery 1417:1424 Recovery 1417:1424 Recovery from the disturbance 1417:1445 Recovery from the disturbance was evidenced with a simultaneous decrease in the above mentioned quantities. 24999116 1 46 theme wastewater 203:212 arg1 treatment 214:222 wastewater treatment 203:222 wastewater treatment 203:222 Membrane bioreactors are a well-established technology for wastewater treatment. 24999116 8 47 theme certain 1245:1251 arg1 delay 1253:1257 a certain delay 1243:1257 a certain delay 1243:1257 Following a certain delay, an increase in submicron particles, supernatant proteins, and polysaccharides was observed as well as an increase in the irreversible membrane fouling rate. 24999116 4 48 theme increased 585:593 arg1 performance 604:614 increased membrane performance 585:614 increased membrane performance 585:614 Therefore, improved insight into the impact of fouling is crucial towards increased membrane performance. 24999116 0 49 theme carbon 129:134 arg1 dosing 136:141 powdered activated carbon dosing 110:141 powdered activated carbon dosing 110:141 Salt stress in a membrane bioreactor: dynamics of sludge properties, membrane fouling and remediation through powdered activated carbon dosing. 24999116 7 50 theme fouling 1209:1215 arg1 rate 1217:1220 the total fouling rate 1199:1220 the total fouling rate 1199:1220 Upon salt addition, the supramicron PSD immediately shifted to smaller floc sizes, and the total fouling rate increased. 24999116 5 51 theme parallel 740:747 arg1 bioreactors 768:778 two parallel lab-scale membrane bioreactors 736:778 two parallel lab-scale membrane bioreactors 736:778 In this work, the disturbance of a salt shock was investigated with respect to sludge composition and filterability in two parallel lab-scale membrane bioreactors. 24999116 9 52 theme mentioned 1503:1511 arg1 quantities 1513:1522 the above mentioned quantities 1493:1522 the above mentioned quantities 1493:1522 Recovery from the disturbance was evidenced with a simultaneous decrease in the above mentioned quantities. 24999116 0 53 theme membrane 17:24 arg1 bioreactor 26:35 a membrane bioreactor 15:35 a membrane bioreactor 15:35 Salt stress in a membrane bioreactor: dynamics of sludge properties, membrane fouling and remediation through powdered activated carbon dosing. 24999116 0 54 theme activated 119:127 arg1 dosing 136:141 powdered activated carbon dosing 110:141 powdered activated carbon dosing 110:141 Salt stress in a membrane bioreactor: dynamics of sludge properties, membrane fouling and remediation through powdered activated carbon dosing. 24999116 8 55 theme supernatant 1296:1306 arg1 proteins 1308:1315 supernatant proteins 1296:1315 supernatant proteins 1296:1315 Following a certain delay, an increase in submicron particles, supernatant proteins, and polysaccharides was observed as well as an increase in the irreversible membrane fouling rate. 24999116 7 56 theme smaller 1175:1181 arg1 sizes 1188:1192 smaller floc sizes 1175:1192 smaller floc sizes 1175:1192 Upon salt addition, the supramicron PSD immediately shifted to smaller floc sizes, and the total fouling rate increased. 24999116 10 57 theme carbon 1577:1582 arg1 addition 1590:1597 powdered activated carbon (PAC) addition 1558:1597 powdered activated carbon (PAC) addition used for remediation 1558:1618 A similar experiment introducing powdered activated carbon (PAC) addition used for remediation resulted in either no or less significant changes in the above mentioned quantities, signifying its potential as a mitigation strategy. 24999116 6 58 theme size 910:913 arg1 distributions 915:927 supramicron particle size distributions 889:927 supramicron particle size distributions (PSD) 889:933 Several key sludge parameters (soluble microbial products, sludge-bound extracellular polymeric substances, supramicron particle size distributions (PSD), submicron particle concentrations) were intensively monitored prior to, during, and after a disturbance to investigate its impact as well as the potential governing mechanism. 24999116 6 58 theme size 910:913 arg1 products 830:837 soluble microbial products 812:837 soluble microbial products 812:837 Several key sludge parameters (soluble microbial products, sludge-bound extracellular polymeric substances, supramicron particle size distributions (PSD), submicron particle concentrations) were intensively monitored prior to, during, and after a disturbance to investigate its impact as well as the potential governing mechanism. 24999116 6 58 theme size 910:913 arg1 PSD 930:932 PSD 930:932 PSD 930:932 Several key sludge parameters (soluble microbial products, sludge-bound extracellular polymeric substances, supramicron particle size distributions (PSD), submicron particle concentrations) were intensively monitored prior to, during, and after a disturbance to investigate its impact as well as the potential governing mechanism. 24999116 6 59 theme sludge 793:798 arg1 parameters 800:809 Several key sludge parameters 781:809 Several key sludge parameters (soluble microbial products, sludge-bound extracellular polymeric substances, supramicron particle size distributions (PSD), submicron particle concentrations) 781:969 Several key sludge parameters (soluble microbial products, sludge-bound extracellular polymeric substances, supramicron particle size distributions (PSD), submicron particle concentrations) were intensively monitored prior to, during, and after a disturbance to investigate its impact as well as the potential governing mechanism. 24999116 3 60 theme fouling 425:431 arg1 propensity 433:442 This fouling propensity 420:442 This fouling propensity of the activated sludge 420:466 This fouling propensity of the activated sludge is closely related to system disturbances. 24999116 5 61 theme sludge 696:701 arg1 composition 703:713 sludge composition 696:713 sludge composition 696:713 In this work, the disturbance of a salt shock was investigated with respect to sludge composition and filterability in two parallel lab-scale membrane bioreactors. 24999116 6 62 theme particle 901:908 arg1 size 910:913 supramicron particle size 889:913 supramicron particle size distributions (PSD) 889:933 Several key sludge parameters (soluble microbial products, sludge-bound extracellular polymeric substances, supramicron particle size distributions (PSD), submicron particle concentrations) were intensively monitored prior to, during, and after a disturbance to investigate its impact as well as the potential governing mechanism. 24999116 6 63 theme key 789:791 arg1 parameters 800:809 Several key sludge parameters 781:809 Several key sludge parameters (soluble microbial products, sludge-bound extracellular polymeric substances, supramicron particle size distributions (PSD), submicron particle concentrations) 781:969 Several key sludge parameters (soluble microbial products, sludge-bound extracellular polymeric substances, supramicron particle size distributions (PSD), submicron particle concentrations) were intensively monitored prior to, during, and after a disturbance to investigate its impact as well as the potential governing mechanism. 24999116 10 64 theme mitigation 1735:1744 arg1 strategy 1746:1753 a mitigation strategy 1733:1753 a mitigation strategy 1733:1753 A similar experiment introducing powdered activated carbon (PAC) addition used for remediation resulted in either no or less significant changes in the above mentioned quantities, signifying its potential as a mitigation strategy. 24999116 4 65 theme fouling 558:564 arg1 impact 548:553 the impact 544:553 the impact of fouling 544:564 Therefore, improved insight into the impact of fouling is crucial towards increased membrane performance. 24999116 10 66 theme powdered 1558:1565 arg1 addition 1590:1597 powdered activated carbon (PAC) addition 1558:1597 powdered activated carbon (PAC) addition used for remediation 1558:1618 A similar experiment introducing powdered activated carbon (PAC) addition used for remediation resulted in either no or less significant changes in the above mentioned quantities, signifying its potential as a mitigation strategy. 24999116 6 67 theme supramicron 889:899 arg1 size 910:913 supramicron particle size 889:913 supramicron particle size distributions (PSD) 889:933 Several key sludge parameters (soluble microbial products, sludge-bound extracellular polymeric substances, supramicron particle size distributions (PSD), submicron particle concentrations) were intensively monitored prior to, during, and after a disturbance to investigate its impact as well as the potential governing mechanism. 24999116 2 68 from perspective 407:417 arg1 appealing 380:388 appealing 380:388 appealing 380:388 However, their efficiency is adversely impacted by membrane fouling, primarily inciting very conservative operations of installations that makes them less appealing from an economic perspective. 24999116 2 69 theme installations 345:357 arg1 operations 331:340 very conservative operations 313:340 very conservative operations of installations that makes them less appealing from an economic perspective 313:417 However, their efficiency is adversely impacted by membrane fouling, primarily inciting very conservative operations of installations that makes them less appealing from an economic perspective. 24999116 8 70 from increase 1263:1270 arg1 polysaccharides 1322:1336 polysaccharides 1322:1336 polysaccharides 1322:1336 Following a certain delay, an increase in submicron particles, supernatant proteins, and polysaccharides was observed as well as an increase in the irreversible membrane fouling rate. 24999116 8 70 from increase 1263:1270 arg1 particles 1285:1293 submicron particles 1275:1293 submicron particles 1275:1293 Following a certain delay, an increase in submicron particles, supernatant proteins, and polysaccharides was observed as well as an increase in the irreversible membrane fouling rate. 24999116 8 70 from increase 1263:1270 arg1 proteins 1308:1315 supernatant proteins 1296:1315 supernatant proteins 1296:1315 Following a certain delay, an increase in submicron particles, supernatant proteins, and polysaccharides was observed as well as an increase in the irreversible membrane fouling rate. 24999116 5 71 from composition 703:713 arg1 bioreactors 768:778 two parallel lab-scale membrane bioreactors 736:778 two parallel lab-scale membrane bioreactors 736:778 In this work, the disturbance of a salt shock was investigated with respect to sludge composition and filterability in two parallel lab-scale membrane bioreactors. 24999116 6 72 theme Several 781:787 arg1 parameters 800:809 Several key sludge parameters 781:809 Several key sludge parameters (soluble microbial products, sludge-bound extracellular polymeric substances, supramicron particle size distributions (PSD), submicron particle concentrations) 781:969 Several key sludge parameters (soluble microbial products, sludge-bound extracellular polymeric substances, supramicron particle size distributions (PSD), submicron particle concentrations) were intensively monitored prior to, during, and after a disturbance to investigate its impact as well as the potential governing mechanism. 24999116 9 73 from decrease 1481:1488 arg1 quantities 1513:1522 the above mentioned quantities 1493:1522 the above mentioned quantities 1493:1522 Recovery from the disturbance was evidenced with a simultaneous decrease in the above mentioned quantities. 24999116 8 74 from increase 1365:1372 arg1 rate 1411:1414 the irreversible membrane fouling rate 1377:1414 the irreversible membrane fouling rate 1377:1414 Following a certain delay, an increase in submicron particles, supernatant proteins, and polysaccharides was observed as well as an increase in the irreversible membrane fouling rate. 24999116 0 75 theme sludge 50:55 arg1 properties 57:66 sludge properties 50:66 sludge properties 50:66 Salt stress in a membrane bioreactor: dynamics of sludge properties, membrane fouling and remediation through powdered activated carbon dosing. 24999116 0 76 dep stress 5:10 arg1 fouling 78:84 membrane fouling 69:84 membrane fouling 69:84 Salt stress in a membrane bioreactor: dynamics of sludge properties, membrane fouling and remediation through powdered activated carbon dosing. 24999116 0 76 dep stress 5:10 arg1 remediation 90:100 remediation 90:100 remediation 90:100 Salt stress in a membrane bioreactor: dynamics of sludge properties, membrane fouling and remediation through powdered activated carbon dosing. 24999116 0 76 dep stress 5:10 arg1 dynamics 38:45 dynamics 38:45 dynamics of sludge properties 38:66 Salt stress in a membrane bioreactor: dynamics of sludge properties, membrane fouling and remediation through powdered activated carbon dosing. 24999116 10 77 theme mentioned 1683:1691 arg1 quantities 1693:1702 the above mentioned quantities 1673:1702 the above mentioned quantities 1673:1702 A similar experiment introducing powdered activated carbon (PAC) addition used for remediation resulted in either no or less significant changes in the above mentioned quantities, signifying its potential as a mitigation strategy. 24999116 10 78 theme significant 1650:1660 arg1 changes 1662:1668 less significant changes 1645:1668 less significant changes in the above mentioned quantities 1645:1702 A similar experiment introducing powdered activated carbon (PAC) addition used for remediation resulted in either no or less significant changes in the above mentioned quantities, signifying its potential as a mitigation strategy. 24999116 5 79 theme membrane 759:766 arg1 bioreactors 768:778 two parallel lab-scale membrane bioreactors 736:778 two parallel lab-scale membrane bioreactors 736:778 In this work, the disturbance of a salt shock was investigated with respect to sludge composition and filterability in two parallel lab-scale membrane bioreactors. 29081768 10 0 theme habit 2089:2093 arg1 modifications 2095:2107 dietary habit modifications 2081:2107 dietary habit modifications in the course of urbanization 2081:2137 Our results even if in a limited number of individuals point out that dietary habit modifications in the course of urbanization play a role in shaping gut microbiota, and that ancient microorganisms, such as fiber-degrading bacteria, are at risk of being eliminated by the fast paced globalization of foods and by the advent of westernized lifestyle. 29081768 8 1 theme foods 1593:1597 arg1 metabolism 1544:1553 the metabolism 1540:1553 the metabolism of animal protein, fat and sugar rich foods 1540:1597 Independently of geography and ethnicity, in children living in urban areas these bacterial genera were progressively outcompeted by bacteria more suited to the metabolism of animal protein, fat and sugar rich foods, similarly to Italian children, as resulted by PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States), a predictive functional profiling of microbial communities using 16S rRNA marker gene. 29081768 5 2 theme = 977:977 arg1 n 975:975 n = 13 975:980 n = 13 975:980 We analyzed dietary habits and, by pyrosequencing of the 16S rRNA gene, gut microbiota profiles from fecal samples of children living in a rural village of Burkina Faso (n = 11), of two groups of children living in different urban settings (Nanoro town, n = 8; Ouagadougou, the capital city, n = 5) and of a group of Italian children (n = 13). 29081768 5 2 theme = 977:977 arg1 group 948:952 a group 946:952 a group of Italian children (n = 13) 946:981 We analyzed dietary habits and, by pyrosequencing of the 16S rRNA gene, gut microbiota profiles from fecal samples of children living in a rural village of Burkina Faso (n = 11), of two groups of children living in different urban settings (Nanoro town, n = 8; Ouagadougou, the capital city, n = 5) and of a group of Italian children (n = 13). 29081768 5 2 theme = 977:977 arg1 children 965:972 Italian children 957:972 Italian children 957:972 We analyzed dietary habits and, by pyrosequencing of the 16S rRNA gene, gut microbiota profiles from fecal samples of children living in a rural village of Burkina Faso (n = 11), of two groups of children living in different urban settings (Nanoro town, n = 8; Ouagadougou, the capital city, n = 5) and of a group of Italian children (n = 13). 29081768 7 3 theme rural 1210:1214 arg1 children 1216:1223 rural children 1210:1223 rural children 1210:1223 Microbiota of rural children retain a geographically unique bacterial reservoir (Prevotella, Treponema, and Succinivibrio), assigned to ferment fiber and polysaccharides from vegetables. 29081768 5 4 dep town 888:891 arg1 n 894:894 n = 8 894:898 n = 8 894:898 We analyzed dietary habits and, by pyrosequencing of the 16S rRNA gene, gut microbiota profiles from fecal samples of children living in a rural village of Burkina Faso (n = 11), of two groups of children living in different urban settings (Nanoro town, n = 8; Ouagadougou, the capital city, n = 5) and of a group of Italian children (n = 13). 29081768 5 4 dep town 888:891 arg1 city 926:929 the capital city 914:929 the capital city 914:929 We analyzed dietary habits and, by pyrosequencing of the 16S rRNA gene, gut microbiota profiles from fecal samples of children living in a rural village of Burkina Faso (n = 11), of two groups of children living in different urban settings (Nanoro town, n = 8; Ouagadougou, the capital city, n = 5) and of a group of Italian children (n = 13). 29081768 5 4 dep town 888:891 arg1 Ouagadougou 901:911 Ouagadougou 901:911 Ouagadougou 901:911 We analyzed dietary habits and, by pyrosequencing of the 16S rRNA gene, gut microbiota profiles from fecal samples of children living in a rural village of Burkina Faso (n = 11), of two groups of children living in different urban settings (Nanoro town, n = 8; Ouagadougou, the capital city, n = 5) and of a group of Italian children (n = 13). 29081768 5 4 dep town 888:891 arg1 n 932:932 n = 5 932:936 n = 5 932:936 We analyzed dietary habits and, by pyrosequencing of the 16S rRNA gene, gut microbiota profiles from fecal samples of children living in a rural village of Burkina Faso (n = 11), of two groups of children living in different urban settings (Nanoro town, n = 8; Ouagadougou, the capital city, n = 5) and of a group of Italian children (n = 13). 29081768 9 5 theme SCFAs 1878:1882 arg1 reduction 1865:1873 a progressive reduction 1851:1873 a progressive reduction of SCFAs measured by gas chromatography-mass spectrometry 1851:1931 Consequently, we observed a progressive reduction of SCFAs measured by gas chromatography-mass spectrometry, in urban populations, especially in Italian children, respect to rural ones. 29081768 6 6 theme origin 1022:1027 arg1 foods 1006:1010 foods 1006:1010 foods of animal origin 1006:1027 We observed that when foods of animal origin, those rich in fat and simple sugars are introduced into a traditional African diet, composed of cereals, legumes and vegetables, the gut microbiota profiles changes. 29081768 8 7 theme urban 1447:1451 arg1 areas 1453:1457 urban areas 1447:1457 urban areas 1447:1457 Independently of geography and ethnicity, in children living in urban areas these bacterial genera were progressively outcompeted by bacteria more suited to the metabolism of animal protein, fat and sugar rich foods, similarly to Italian children, as resulted by PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States), a predictive functional profiling of microbial communities using 16S rRNA marker gene. 29081768 10 8 dep point 2066:2070 arg1 out 2072:2074 out 2072:2074 out 2072:2074 Our results even if in a limited number of individuals point out that dietary habit modifications in the course of urbanization play a role in shaping gut microbiota, and that ancient microorganisms, such as fiber-degrading bacteria, are at risk of being eliminated by the fast paced globalization of foods and by the advent of westernized lifestyle. 29081768 10 9 theme limited 2036:2042 arg1 number 2044:2049 a limited number 2034:2049 a limited number of individuals 2034:2064 Our results even if in a limited number of individuals point out that dietary habit modifications in the course of urbanization play a role in shaping gut microbiota, and that ancient microorganisms, such as fiber-degrading bacteria, are at risk of being eliminated by the fast paced globalization of foods and by the advent of westernized lifestyle. 29081768 8 10 theme Italian 1613:1619 arg1 children 1621:1628 Italian children 1613:1628 Italian children 1613:1628 Independently of geography and ethnicity, in children living in urban areas these bacterial genera were progressively outcompeted by bacteria more suited to the metabolism of animal protein, fat and sugar rich foods, similarly to Italian children, as resulted by PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States), a predictive functional profiling of microbial communities using 16S rRNA marker gene. 29081768 8 11 theme predictive 1740:1749 arg1 profiling 1762:1770 a predictive functional profiling 1738:1770 a predictive functional profiling of microbial communities using 16S rRNA marker gene 1738:1822 Independently of geography and ethnicity, in children living in urban areas these bacterial genera were progressively outcompeted by bacteria more suited to the metabolism of animal protein, fat and sugar rich foods, similarly to Italian children, as resulted by PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States), a predictive functional profiling of microbial communities using 16S rRNA marker gene. 29081768 8 11 theme predictive 1740:1749 arg1 PICRUSt 1646:1652 PICRUSt 1646:1652 PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) 1646:1735 Independently of geography and ethnicity, in children living in urban areas these bacterial genera were progressively outcompeted by bacteria more suited to the metabolism of animal protein, fat and sugar rich foods, similarly to Italian children, as resulted by PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States), a predictive functional profiling of microbial communities using 16S rRNA marker gene. 29081768 5 12 theme children 758:765 arg1 samples 747:753 fecal samples 741:753 fecal samples of children living in a rural village of Burkina Faso (n = 11), of two groups of children living in different urban settings (Nanoro town, n = 8; Ouagadougou, the capital city, n = 5) and of a group of Italian children (n = 13) 741:981 We analyzed dietary habits and, by pyrosequencing of the 16S rRNA gene, gut microbiota profiles from fecal samples of children living in a rural village of Burkina Faso (n = 11), of two groups of children living in different urban settings (Nanoro town, n = 8; Ouagadougou, the capital city, n = 5) and of a group of Italian children (n = 13). 29081768 9 13 theme chromatography-mass 1900:1918 arg1 spectrometry 1920:1931 gas chromatography-mass spectrometry 1896:1931 gas chromatography-mass spectrometry 1896:1931 Consequently, we observed a progressive reduction of SCFAs measured by gas chromatography-mass spectrometry, in urban populations, especially in Italian children, respect to rural ones. 29081768 1 14 theme Urban 100:104 arg1 Faso 114:117 Rural and Urban Burkina Faso 90:117 Rural and Urban Burkina Faso 90:117 A Preliminary Investigation in Children Living in Rural and Urban Burkina Faso and Italy. 29081768 10 15 from modifications 2095:2107 arg1 course 2116:2121 the course 2112:2121 the course of urbanization 2112:2137 Our results even if in a limited number of individuals point out that dietary habit modifications in the course of urbanization play a role in shaping gut microbiota, and that ancient microorganisms, such as fiber-degrading bacteria, are at risk of being eliminated by the fast paced globalization of foods and by the advent of westernized lifestyle. 29081768 10 16 theme fiber-degrading 2219:2233 arg1 bacteria 2235:2242 fiber-degrading bacteria 2219:2242 fiber-degrading bacteria 2219:2242 Our results even if in a limited number of individuals point out that dietary habit modifications in the course of urbanization play a role in shaping gut microbiota, and that ancient microorganisms, such as fiber-degrading bacteria, are at risk of being eliminated by the fast paced globalization of foods and by the advent of westernized lifestyle. 29081768 9 17 theme urban 1937:1941 arg1 populations 1943:1953 urban populations 1937:1953 urban populations 1937:1953 Consequently, we observed a progressive reduction of SCFAs measured by gas chromatography-mass spectrometry, in urban populations, especially in Italian children, respect to rural ones. 29081768 3 18 theme urban 255:259 arg1 areas 261:265 urban areas 255:265 urban areas 255:265 When people move from a rural environment to urban areas, and experience improved socio-economic conditions, they are often exposed to a "globalized" Western type diet. 29081768 8 19 theme Phylogenetic 1655:1666 arg1 Investigation 1668:1680 Phylogenetic Investigation 1655:1680 Phylogenetic Investigation of Communities by Reconstruction of Unobserved States 1655:1734 Independently of geography and ethnicity, in children living in urban areas these bacterial genera were progressively outcompeted by bacteria more suited to the metabolism of animal protein, fat and sugar rich foods, similarly to Italian children, as resulted by PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States), a predictive functional profiling of microbial communities using 16S rRNA marker gene. 29081768 5 20 theme Faso 804:807 arg1 village 785:791 a rural village 777:791 a rural village of Burkina Faso (n = 11), of two groups of children living in different urban settings (Nanoro town, n = 8; Ouagadougou, the capital city, n = 5) and of a group of Italian children (n = 13) 777:981 We analyzed dietary habits and, by pyrosequencing of the 16S rRNA gene, gut microbiota profiles from fecal samples of children living in a rural village of Burkina Faso (n = 11), of two groups of children living in different urban settings (Nanoro town, n = 8; Ouagadougou, the capital city, n = 5) and of a group of Italian children (n = 13). 29081768 2 21 theme microbiota 198:207 arg1 composition 179:189 the composition 175:189 the composition of gut microbiota 175:207 Diet is one of the main factors that affects the composition of gut microbiota. 29081768 5 22 theme rural 779:783 arg1 village 785:791 a rural village 777:791 a rural village of Burkina Faso (n = 11), of two groups of children living in different urban settings (Nanoro town, n = 8; Ouagadougou, the capital city, n = 5) and of a group of Italian children (n = 13) 777:981 We analyzed dietary habits and, by pyrosequencing of the 16S rRNA gene, gut microbiota profiles from fecal samples of children living in a rural village of Burkina Faso (n = 11), of two groups of children living in different urban settings (Nanoro town, n = 8; Ouagadougou, the capital city, n = 5) and of a group of Italian children (n = 13). 29081768 4 23 theme metagenomic 428:438 arg1 scale 440:444 the metagenomic scale 424:444 the metagenomic scale of microbial changes in small groups of African children belonging to the same ethnicity and living in different environments 424:570 Here, we present preliminary observations on the metagenomic scale of microbial changes in small groups of African children belonging to the same ethnicity and living in different environments, compared to children living on the urban area of Florence (Italy). 29081768 4 24 theme Florence 622:629 arg1 area 614:617 the urban area 604:617 the urban area of Florence (Italy) 604:637 Here, we present preliminary observations on the metagenomic scale of microbial changes in small groups of African children belonging to the same ethnicity and living in different environments, compared to children living on the urban area of Florence (Italy). 29081768 8 25 theme animal 1558:1563 arg1 protein 1565:1571 animal protein 1558:1571 animal protein 1558:1571 Independently of geography and ethnicity, in children living in urban areas these bacterial genera were progressively outcompeted by bacteria more suited to the metabolism of animal protein, fat and sugar rich foods, similarly to Italian children, as resulted by PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States), a predictive functional profiling of microbial communities using 16S rRNA marker gene. 29081768 9 26 theme rural 1999:2003 arg1 ones 2005:2008 rural ones 1999:2008 rural ones 1999:2008 Consequently, we observed a progressive reduction of SCFAs measured by gas chromatography-mass spectrometry, in urban populations, especially in Italian children, respect to rural ones. 29081768 8 27 theme States 1729:1734 arg1 Reconstruction 1700:1713 Reconstruction 1700:1713 Reconstruction of Unobserved States 1700:1734 Independently of geography and ethnicity, in children living in urban areas these bacterial genera were progressively outcompeted by bacteria more suited to the metabolism of animal protein, fat and sugar rich foods, similarly to Italian children, as resulted by PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States), a predictive functional profiling of microbial communities using 16S rRNA marker gene. 29081768 1 28 theme Preliminary 42:52 arg1 Investigation 54:66 A Preliminary Investigation 40:66 A Preliminary Investigation in Children 40:78 A Preliminary Investigation in Children Living in Rural and Urban Burkina Faso and Italy. 29081768 3 29 theme socio-economic 292:305 arg1 conditions 307:316 improved socio-economic conditions 283:316 improved socio-economic conditions 283:316 When people move from a rural environment to urban areas, and experience improved socio-economic conditions, they are often exposed to a "globalized" Western type diet. 29081768 4 30 theme preliminary 396:406 arg1 observations 408:419 preliminary observations 396:419 preliminary observations on the metagenomic scale of microbial changes in small groups of African children belonging to the same ethnicity and living in different environments 396:570 Here, we present preliminary observations on the metagenomic scale of microbial changes in small groups of African children belonging to the same ethnicity and living in different environments, compared to children living on the urban area of Florence (Italy). 29081768 10 31 theme paced 2289:2293 arg1 globalization 2295:2307 the fast paced globalization 2280:2307 the fast paced globalization of foods 2280:2316 Our results even if in a limited number of individuals point out that dietary habit modifications in the course of urbanization play a role in shaping gut microbiota, and that ancient microorganisms, such as fiber-degrading bacteria, are at risk of being eliminated by the fast paced globalization of foods and by the advent of westernized lifestyle. 29081768 0 32 theme Gut 24:26 arg1 Microbiota 28:37 Gut Microbiota 24:37 Gut Microbiota 24:37 Diet, Environments, and Gut Microbiota. 29081768 8 33 theme rRNA 1807:1810 arg1 gene 1819:1822 16S rRNA marker gene 1803:1822 16S rRNA marker gene 1803:1822 Independently of geography and ethnicity, in children living in urban areas these bacterial genera were progressively outcompeted by bacteria more suited to the metabolism of animal protein, fat and sugar rich foods, similarly to Italian children, as resulted by PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States), a predictive functional profiling of microbial communities using 16S rRNA marker gene. 29081768 10 34 theme gut 2162:2164 arg1 microbiota 2166:2175 shaping gut microbiota 2154:2175 shaping gut microbiota 2154:2175 Our results even if in a limited number of individuals point out that dietary habit modifications in the course of urbanization play a role in shaping gut microbiota, and that ancient microorganisms, such as fiber-degrading bacteria, are at risk of being eliminated by the fast paced globalization of foods and by the advent of westernized lifestyle. 29081768 3 35 theme Western 360:366 arg1 type 368:371 a "globalized" Western type 345:371 a "globalized" Western type diet 345:376 When people move from a rural environment to urban areas, and experience improved socio-economic conditions, they are often exposed to a "globalized" Western type diet. 29081768 6 36 theme gut 1163:1165 arg1 profiles 1178:1185 the gut microbiota profiles 1159:1185 the gut microbiota profiles 1159:1185 We observed that when foods of animal origin, those rich in fat and simple sugars are introduced into a traditional African diet, composed of cereals, legumes and vegetables, the gut microbiota profiles changes. 29081768 6 36 theme gut 1163:1165 arg1 vegetables 1147:1156 vegetables 1147:1156 vegetables 1147:1156 We observed that when foods of animal origin, those rich in fat and simple sugars are introduced into a traditional African diet, composed of cereals, legumes and vegetables, the gut microbiota profiles changes. 29081768 8 37 theme rich 1588:1591 arg1 foods 1593:1597 sugar rich foods 1582:1597 sugar rich foods 1582:1597 Independently of geography and ethnicity, in children living in urban areas these bacterial genera were progressively outcompeted by bacteria more suited to the metabolism of animal protein, fat and sugar rich foods, similarly to Italian children, as resulted by PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States), a predictive functional profiling of microbial communities using 16S rRNA marker gene. 29081768 5 38 theme microbiota 716:725 arg1 profiles 727:734 gut microbiota profiles 712:734 gut microbiota profiles from fecal samples of children living in a rural village of Burkina Faso (n = 11), of two groups of children living in different urban settings (Nanoro town, n = 8; Ouagadougou, the capital city, n = 5) and of a group of Italian children (n = 13) 712:981 We analyzed dietary habits and, by pyrosequencing of the 16S rRNA gene, gut microbiota profiles from fecal samples of children living in a rural village of Burkina Faso (n = 11), of two groups of children living in different urban settings (Nanoro town, n = 8; Ouagadougou, the capital city, n = 5) and of a group of Italian children (n = 13). 29081768 5 39 theme children 965:972 arg1 n 975:975 n = 13 975:980 n = 13 975:980 We analyzed dietary habits and, by pyrosequencing of the 16S rRNA gene, gut microbiota profiles from fecal samples of children living in a rural village of Burkina Faso (n = 11), of two groups of children living in different urban settings (Nanoro town, n = 8; Ouagadougou, the capital city, n = 5) and of a group of Italian children (n = 13). 29081768 5 39 theme children 965:972 arg1 group 948:952 a group 946:952 a group of Italian children (n = 13) 946:981 We analyzed dietary habits and, by pyrosequencing of the 16S rRNA gene, gut microbiota profiles from fecal samples of children living in a rural village of Burkina Faso (n = 11), of two groups of children living in different urban settings (Nanoro town, n = 8; Ouagadougou, the capital city, n = 5) and of a group of Italian children (n = 13). 29081768 5 39 theme children 965:972 arg1 children 965:972 Italian children 957:972 Italian children 957:972 We analyzed dietary habits and, by pyrosequencing of the 16S rRNA gene, gut microbiota profiles from fecal samples of children living in a rural village of Burkina Faso (n = 11), of two groups of children living in different urban settings (Nanoro town, n = 8; Ouagadougou, the capital city, n = 5) and of a group of Italian children (n = 13). 29081768 1 40 theme Rural 90:94 arg1 Faso 114:117 Rural and Urban Burkina Faso 90:117 Rural and Urban Burkina Faso 90:117 A Preliminary Investigation in Children Living in Rural and Urban Burkina Faso and Italy. 29081768 3 41 theme globalized 348:357 arg1 type 368:371 a "globalized" Western type 345:371 a "globalized" Western type diet 345:376 When people move from a rural environment to urban areas, and experience improved socio-economic conditions, they are often exposed to a "globalized" Western type diet. 29081768 4 42 theme children 494:501 arg1 groups 476:481 small groups 470:481 small groups of African children belonging to the same ethnicity and living in different environments 470:570 Here, we present preliminary observations on the metagenomic scale of microbial changes in small groups of African children belonging to the same ethnicity and living in different environments, compared to children living on the urban area of Florence (Italy). 29081768 4 42 theme children 494:501 arg1 children 494:501 African children 486:501 African children belonging to the same ethnicity and living in different environments 486:570 Here, we present preliminary observations on the metagenomic scale of microbial changes in small groups of African children belonging to the same ethnicity and living in different environments, compared to children living on the urban area of Florence (Italy). 29081768 10 43 theme lifestyle 2351:2359 arg1 advent 2329:2334 the advent 2325:2334 the advent of westernized lifestyle 2325:2359 Our results even if in a limited number of individuals point out that dietary habit modifications in the course of urbanization play a role in shaping gut microbiota, and that ancient microorganisms, such as fiber-degrading bacteria, are at risk of being eliminated by the fast paced globalization of foods and by the advent of westernized lifestyle. 29081768 8 44 theme microbial 1775:1783 arg1 communities 1785:1795 microbial communities 1775:1795 microbial communities using 16S rRNA marker gene 1775:1822 Independently of geography and ethnicity, in children living in urban areas these bacterial genera were progressively outcompeted by bacteria more suited to the metabolism of animal protein, fat and sugar rich foods, similarly to Italian children, as resulted by PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States), a predictive functional profiling of microbial communities using 16S rRNA marker gene. 29081768 6 45 from fat 1044:1046 arg1 rich 1036:1039 rich 1036:1039 rich 1036:1039 We observed that when foods of animal origin, those rich in fat and simple sugars are introduced into a traditional African diet, composed of cereals, legumes and vegetables, the gut microbiota profiles changes. 29081768 8 46 dep PICRUSt 1646:1652 arg1 Investigation 1668:1680 Phylogenetic Investigation 1655:1680 Phylogenetic Investigation of Communities by Reconstruction of Unobserved States 1655:1734 Independently of geography and ethnicity, in children living in urban areas these bacterial genera were progressively outcompeted by bacteria more suited to the metabolism of animal protein, fat and sugar rich foods, similarly to Italian children, as resulted by PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States), a predictive functional profiling of microbial communities using 16S rRNA marker gene. 29081768 4 47 theme changes 459:465 arg1 scale 440:444 the metagenomic scale 424:444 the metagenomic scale of microbial changes in small groups of African children belonging to the same ethnicity and living in different environments 424:570 Here, we present preliminary observations on the metagenomic scale of microbial changes in small groups of African children belonging to the same ethnicity and living in different environments, compared to children living on the urban area of Florence (Italy). 29081768 5 48 theme rRNA 701:704 arg1 gene 706:709 the 16S rRNA gene 693:709 the 16S rRNA gene 693:709 We analyzed dietary habits and, by pyrosequencing of the 16S rRNA gene, gut microbiota profiles from fecal samples of children living in a rural village of Burkina Faso (n = 11), of two groups of children living in different urban settings (Nanoro town, n = 8; Ouagadougou, the capital city, n = 5) and of a group of Italian children (n = 13). 29081768 7 49 theme unique 1249:1254 arg1 reservoir 1266:1274 a geographically unique bacterial reservoir 1232:1274 a geographically unique bacterial reservoir (Prevotella, Treponema, and Succinivibrio) 1232:1317 Microbiota of rural children retain a geographically unique bacterial reservoir (Prevotella, Treponema, and Succinivibrio), assigned to ferment fiber and polysaccharides from vegetables. 29081768 5 50 theme Nanoro 881:886 arg1 settings 871:878 different urban settings 855:878 different urban settings (Nanoro town, n = 8; Ouagadougou, the capital city, n = 5) 855:937 We analyzed dietary habits and, by pyrosequencing of the 16S rRNA gene, gut microbiota profiles from fecal samples of children living in a rural village of Burkina Faso (n = 11), of two groups of children living in different urban settings (Nanoro town, n = 8; Ouagadougou, the capital city, n = 5) and of a group of Italian children (n = 13). 29081768 5 50 theme Nanoro 881:886 arg1 town 888:891 Nanoro town 881:891 Nanoro town 881:891 We analyzed dietary habits and, by pyrosequencing of the 16S rRNA gene, gut microbiota profiles from fecal samples of children living in a rural village of Burkina Faso (n = 11), of two groups of children living in different urban settings (Nanoro town, n = 8; Ouagadougou, the capital city, n = 5) and of a group of Italian children (n = 13). 29081768 4 51 theme small 470:474 arg1 groups 476:481 small groups 470:481 small groups of African children belonging to the same ethnicity and living in different environments 470:570 Here, we present preliminary observations on the metagenomic scale of microbial changes in small groups of African children belonging to the same ethnicity and living in different environments, compared to children living on the urban area of Florence (Italy). 29081768 4 51 theme small 470:474 arg1 children 494:501 African children 486:501 African children belonging to the same ethnicity and living in different environments 486:570 Here, we present preliminary observations on the metagenomic scale of microbial changes in small groups of African children belonging to the same ethnicity and living in different environments, compared to children living on the urban area of Florence (Italy). 29081768 7 52 dep reservoir 1266:1274 arg1 Succinivibrio 1304:1316 Succinivibrio 1304:1316 Succinivibrio 1304:1316 Microbiota of rural children retain a geographically unique bacterial reservoir (Prevotella, Treponema, and Succinivibrio), assigned to ferment fiber and polysaccharides from vegetables. 29081768 7 52 dep reservoir 1266:1274 arg1 Prevotella 1277:1286 Prevotella 1277:1286 Prevotella 1277:1286 Microbiota of rural children retain a geographically unique bacterial reservoir (Prevotella, Treponema, and Succinivibrio), assigned to ferment fiber and polysaccharides from vegetables. 29081768 10 53 theme urbanization 2126:2137 arg1 course 2116:2121 the course 2112:2121 the course of urbanization 2112:2137 Our results even if in a limited number of individuals point out that dietary habit modifications in the course of urbanization play a role in shaping gut microbiota, and that ancient microorganisms, such as fiber-degrading bacteria, are at risk of being eliminated by the fast paced globalization of foods and by the advent of westernized lifestyle. 29081768 2 54 theme main 149:152 arg1 factors 154:160 the main factors 145:160 the main factors 145:160 Diet is one of the main factors that affects the composition of gut microbiota. 29081768 6 55 from rich 1036:1039 arg1 fat 1044:1046 fat 1044:1046 fat 1044:1046 We observed that when foods of animal origin, those rich in fat and simple sugars are introduced into a traditional African diet, composed of cereals, legumes and vegetables, the gut microbiota profiles changes. 29081768 8 56 theme 16S 1803:1805 arg1 gene 1819:1822 16S rRNA marker gene 1803:1822 16S rRNA marker gene 1803:1822 Independently of geography and ethnicity, in children living in urban areas these bacterial genera were progressively outcompeted by bacteria more suited to the metabolism of animal protein, fat and sugar rich foods, similarly to Italian children, as resulted by PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States), a predictive functional profiling of microbial communities using 16S rRNA marker gene. 29081768 7 57 theme children 1216:1223 arg1 Microbiota 1196:1205 Microbiota 1196:1205 Microbiota of rural children 1196:1223 Microbiota of rural children retain a geographically unique bacterial reservoir (Prevotella, Treponema, and Succinivibrio), assigned to ferment fiber and polysaccharides from vegetables. 29081768 5 58 theme different 855:863 arg1 settings 871:878 different urban settings 855:878 different urban settings (Nanoro town, n = 8; Ouagadougou, the capital city, n = 5) 855:937 We analyzed dietary habits and, by pyrosequencing of the 16S rRNA gene, gut microbiota profiles from fecal samples of children living in a rural village of Burkina Faso (n = 11), of two groups of children living in different urban settings (Nanoro town, n = 8; Ouagadougou, the capital city, n = 5) and of a group of Italian children (n = 13). 29081768 5 58 theme different 855:863 arg1 town 888:891 Nanoro town 881:891 Nanoro town 881:891 We analyzed dietary habits and, by pyrosequencing of the 16S rRNA gene, gut microbiota profiles from fecal samples of children living in a rural village of Burkina Faso (n = 11), of two groups of children living in different urban settings (Nanoro town, n = 8; Ouagadougou, the capital city, n = 5) and of a group of Italian children (n = 13). 29081768 9 59 theme progressive 1853:1863 arg1 reduction 1865:1873 a progressive reduction 1851:1873 a progressive reduction of SCFAs measured by gas chromatography-mass spectrometry 1851:1931 Consequently, we observed a progressive reduction of SCFAs measured by gas chromatography-mass spectrometry, in urban populations, especially in Italian children, respect to rural ones. 29081768 6 60 theme rich 1036:1039 arg1 sugars 1059:1064 those rich in fat and simple sugars 1030:1064 those rich in fat and simple sugars 1030:1064 We observed that when foods of animal origin, those rich in fat and simple sugars are introduced into a traditional African diet, composed of cereals, legumes and vegetables, the gut microbiota profiles changes. 29081768 4 61 from scale 440:444 arg1 groups 476:481 small groups 470:481 small groups of African children belonging to the same ethnicity and living in different environments 470:570 Here, we present preliminary observations on the metagenomic scale of microbial changes in small groups of African children belonging to the same ethnicity and living in different environments, compared to children living on the urban area of Florence (Italy). 29081768 4 61 from scale 440:444 arg1 children 494:501 African children 486:501 African children belonging to the same ethnicity and living in different environments 486:570 Here, we present preliminary observations on the metagenomic scale of microbial changes in small groups of African children belonging to the same ethnicity and living in different environments, compared to children living on the urban area of Florence (Italy). 29081768 4 62 theme same 520:523 arg1 ethnicity 525:533 the same ethnicity 516:533 the same ethnicity 516:533 Here, we present preliminary observations on the metagenomic scale of microbial changes in small groups of African children belonging to the same ethnicity and living in different environments, compared to children living on the urban area of Florence (Italy). 29081768 6 63 theme animal 1015:1020 arg1 origin 1022:1027 animal origin 1015:1027 animal origin 1015:1027 We observed that when foods of animal origin, those rich in fat and simple sugars are introduced into a traditional African diet, composed of cereals, legumes and vegetables, the gut microbiota profiles changes. 29081768 4 64 from changes 459:465 arg1 groups 476:481 small groups 470:481 small groups of African children belonging to the same ethnicity and living in different environments 470:570 Here, we present preliminary observations on the metagenomic scale of microbial changes in small groups of African children belonging to the same ethnicity and living in different environments, compared to children living on the urban area of Florence (Italy). 29081768 4 64 from changes 459:465 arg1 children 494:501 African children 486:501 African children belonging to the same ethnicity and living in different environments 486:570 Here, we present preliminary observations on the metagenomic scale of microbial changes in small groups of African children belonging to the same ethnicity and living in different environments, compared to children living on the urban area of Florence (Italy). 29081768 9 65 theme gas 1896:1898 arg1 spectrometry 1920:1931 gas chromatography-mass spectrometry 1896:1931 gas chromatography-mass spectrometry 1896:1931 Consequently, we observed a progressive reduction of SCFAs measured by gas chromatography-mass spectrometry, in urban populations, especially in Italian children, respect to rural ones. 29081768 4 66 from observations 408:419 arg1 scale 440:444 the metagenomic scale 424:444 the metagenomic scale of microbial changes in small groups of African children belonging to the same ethnicity and living in different environments 424:570 Here, we present preliminary observations on the metagenomic scale of microbial changes in small groups of African children belonging to the same ethnicity and living in different environments, compared to children living on the urban area of Florence (Italy). 29081768 10 67 theme ancient 2187:2193 arg1 bacteria 2235:2242 fiber-degrading bacteria 2219:2242 fiber-degrading bacteria 2219:2242 Our results even if in a limited number of individuals point out that dietary habit modifications in the course of urbanization play a role in shaping gut microbiota, and that ancient microorganisms, such as fiber-degrading bacteria, are at risk of being eliminated by the fast paced globalization of foods and by the advent of westernized lifestyle. 29081768 10 67 theme ancient 2187:2193 arg1 microorganisms 2195:2208 ancient microorganisms 2187:2208 ancient microorganisms 2187:2208 Our results even if in a limited number of individuals point out that dietary habit modifications in the course of urbanization play a role in shaping gut microbiota, and that ancient microorganisms, such as fiber-degrading bacteria, are at risk of being eliminated by the fast paced globalization of foods and by the advent of westernized lifestyle. 29081768 8 68 theme bacterial 1465:1473 arg1 genera 1475:1480 these bacterial genera 1459:1480 these bacterial genera 1459:1480 Independently of geography and ethnicity, in children living in urban areas these bacterial genera were progressively outcompeted by bacteria more suited to the metabolism of animal protein, fat and sugar rich foods, similarly to Italian children, as resulted by PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States), a predictive functional profiling of microbial communities using 16S rRNA marker gene. 29081768 3 69 theme rural 234:238 arg1 environment 240:250 a rural environment 232:250 a rural environment 232:250 When people move from a rural environment to urban areas, and experience improved socio-economic conditions, they are often exposed to a "globalized" Western type diet. 29081768 9 70 from respect 1988:1994 arg1 children 1978:1985 Italian children 1970:1985 Italian children 1970:1985 Consequently, we observed a progressive reduction of SCFAs measured by gas chromatography-mass spectrometry, in urban populations, especially in Italian children, respect to rural ones. 29081768 9 70 from respect 1988:1994 arg1 populations 1943:1953 urban populations 1937:1953 urban populations 1937:1953 Consequently, we observed a progressive reduction of SCFAs measured by gas chromatography-mass spectrometry, in urban populations, especially in Italian children, respect to rural ones. 29081768 2 71 theme gut 194:196 arg1 microbiota 198:207 gut microbiota 194:207 gut microbiota 194:207 Diet is one of the main factors that affects the composition of gut microbiota. 29081768 5 72 theme fecal 741:745 arg1 samples 747:753 fecal samples 741:753 fecal samples of children living in a rural village of Burkina Faso (n = 11), of two groups of children living in different urban settings (Nanoro town, n = 8; Ouagadougou, the capital city, n = 5) and of a group of Italian children (n = 13) 741:981 We analyzed dietary habits and, by pyrosequencing of the 16S rRNA gene, gut microbiota profiles from fecal samples of children living in a rural village of Burkina Faso (n = 11), of two groups of children living in different urban settings (Nanoro town, n = 8; Ouagadougou, the capital city, n = 5) and of a group of Italian children (n = 13). 29081768 6 73 theme simple 1052:1057 arg1 sugars 1059:1064 those rich in fat and simple sugars 1030:1064 those rich in fat and simple sugars 1030:1064 We observed that when foods of animal origin, those rich in fat and simple sugars are introduced into a traditional African diet, composed of cereals, legumes and vegetables, the gut microbiota profiles changes. 29081768 5 74 from samples 747:753 arg1 profiles 727:734 gut microbiota profiles 712:734 gut microbiota profiles from fecal samples of children living in a rural village of Burkina Faso (n = 11), of two groups of children living in different urban settings (Nanoro town, n = 8; Ouagadougou, the capital city, n = 5) and of a group of Italian children (n = 13) 712:981 We analyzed dietary habits and, by pyrosequencing of the 16S rRNA gene, gut microbiota profiles from fecal samples of children living in a rural village of Burkina Faso (n = 11), of two groups of children living in different urban settings (Nanoro town, n = 8; Ouagadougou, the capital city, n = 5) and of a group of Italian children (n = 13). 29081768 10 75 theme dietary 2081:2087 arg1 modifications 2095:2107 dietary habit modifications 2081:2107 dietary habit modifications in the course of urbanization 2081:2137 Our results even if in a limited number of individuals point out that dietary habit modifications in the course of urbanization play a role in shaping gut microbiota, and that ancient microorganisms, such as fiber-degrading bacteria, are at risk of being eliminated by the fast paced globalization of foods and by the advent of westernized lifestyle. 29081768 8 76 theme Communities 1685:1695 arg1 Investigation 1668:1680 Phylogenetic Investigation 1655:1680 Phylogenetic Investigation of Communities by Reconstruction of Unobserved States 1655:1734 Independently of geography and ethnicity, in children living in urban areas these bacterial genera were progressively outcompeted by bacteria more suited to the metabolism of animal protein, fat and sugar rich foods, similarly to Italian children, as resulted by PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States), a predictive functional profiling of microbial communities using 16S rRNA marker gene. 29081768 1 77 theme Burkina 106:112 arg1 Faso 114:117 Rural and Urban Burkina Faso 90:117 Rural and Urban Burkina Faso 90:117 A Preliminary Investigation in Children Living in Rural and Urban Burkina Faso and Italy. 29081768 8 78 theme functional 1751:1760 arg1 profiling 1762:1770 a predictive functional profiling 1738:1770 a predictive functional profiling of microbial communities using 16S rRNA marker gene 1738:1822 Independently of geography and ethnicity, in children living in urban areas these bacterial genera were progressively outcompeted by bacteria more suited to the metabolism of animal protein, fat and sugar rich foods, similarly to Italian children, as resulted by PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States), a predictive functional profiling of microbial communities using 16S rRNA marker gene. 29081768 8 78 theme functional 1751:1760 arg1 PICRUSt 1646:1652 PICRUSt 1646:1652 PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) 1646:1735 Independently of geography and ethnicity, in children living in urban areas these bacterial genera were progressively outcompeted by bacteria more suited to the metabolism of animal protein, fat and sugar rich foods, similarly to Italian children, as resulted by PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States), a predictive functional profiling of microbial communities using 16S rRNA marker gene. 29081768 9 79 theme Italian 1970:1976 arg1 children 1978:1985 Italian children 1970:1985 Italian children 1970:1985 Consequently, we observed a progressive reduction of SCFAs measured by gas chromatography-mass spectrometry, in urban populations, especially in Italian children, respect to rural ones. 29081768 5 80 theme = 896:896 arg1 n 894:894 n = 8 894:898 n = 8 894:898 We analyzed dietary habits and, by pyrosequencing of the 16S rRNA gene, gut microbiota profiles from fecal samples of children living in a rural village of Burkina Faso (n = 11), of two groups of children living in different urban settings (Nanoro town, n = 8; Ouagadougou, the capital city, n = 5) and of a group of Italian children (n = 13). 29081768 3 81 theme improved 283:290 arg1 conditions 307:316 improved socio-economic conditions 283:316 improved socio-economic conditions 283:316 When people move from a rural environment to urban areas, and experience improved socio-economic conditions, they are often exposed to a "globalized" Western type diet. 29081768 4 82 theme urban 608:612 arg1 area 614:617 the urban area 604:617 the urban area of Florence (Italy) 604:637 Here, we present preliminary observations on the metagenomic scale of microbial changes in small groups of African children belonging to the same ethnicity and living in different environments, compared to children living on the urban area of Florence (Italy). 29081768 6 83 theme African 1100:1106 arg1 diet 1108:1111 a traditional African diet 1086:1111 a traditional African diet 1086:1111 We observed that when foods of animal origin, those rich in fat and simple sugars are introduced into a traditional African diet, composed of cereals, legumes and vegetables, the gut microbiota profiles changes. 29081768 8 84 theme Unobserved 1718:1727 arg1 States 1729:1734 Unobserved States 1718:1734 Unobserved States 1718:1734 Independently of geography and ethnicity, in children living in urban areas these bacterial genera were progressively outcompeted by bacteria more suited to the metabolism of animal protein, fat and sugar rich foods, similarly to Italian children, as resulted by PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States), a predictive functional profiling of microbial communities using 16S rRNA marker gene. 29081768 5 85 theme = 934:934 arg1 n 932:932 n = 5 932:936 n = 5 932:936 We analyzed dietary habits and, by pyrosequencing of the 16S rRNA gene, gut microbiota profiles from fecal samples of children living in a rural village of Burkina Faso (n = 11), of two groups of children living in different urban settings (Nanoro town, n = 8; Ouagadougou, the capital city, n = 5) and of a group of Italian children (n = 13). 29081768 10 86 theme individuals 2054:2064 arg1 number 2044:2049 a limited number 2034:2049 a limited number of individuals 2034:2064 Our results even if in a limited number of individuals point out that dietary habit modifications in the course of urbanization play a role in shaping gut microbiota, and that ancient microorganisms, such as fiber-degrading bacteria, are at risk of being eliminated by the fast paced globalization of foods and by the advent of westernized lifestyle. 29081768 4 87 theme microbial 449:457 arg1 changes 459:465 microbial changes 449:465 microbial changes in small groups of African children belonging to the same ethnicity and living in different environments 449:570 Here, we present preliminary observations on the metagenomic scale of microbial changes in small groups of African children belonging to the same ethnicity and living in different environments, compared to children living on the urban area of Florence (Italy). 29081768 6 88 theme traditional 1088:1098 arg1 diet 1108:1111 a traditional African diet 1086:1111 a traditional African diet 1086:1111 We observed that when foods of animal origin, those rich in fat and simple sugars are introduced into a traditional African diet, composed of cereals, legumes and vegetables, the gut microbiota profiles changes. 29081768 5 89 theme capital 918:924 arg1 city 926:929 the capital city 914:929 the capital city 914:929 We analyzed dietary habits and, by pyrosequencing of the 16S rRNA gene, gut microbiota profiles from fecal samples of children living in a rural village of Burkina Faso (n = 11), of two groups of children living in different urban settings (Nanoro town, n = 8; Ouagadougou, the capital city, n = 5) and of a group of Italian children (n = 13). 29081768 8 90 theme protein 1565:1571 arg1 metabolism 1544:1553 the metabolism 1540:1553 the metabolism of animal protein, fat and sugar rich foods 1540:1597 Independently of geography and ethnicity, in children living in urban areas these bacterial genera were progressively outcompeted by bacteria more suited to the metabolism of animal protein, fat and sugar rich foods, similarly to Italian children, as resulted by PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States), a predictive functional profiling of microbial communities using 16S rRNA marker gene. 29081768 5 91 theme groups 826:831 arg1 village 785:791 a rural village 777:791 a rural village of Burkina Faso (n = 11), of two groups of children living in different urban settings (Nanoro town, n = 8; Ouagadougou, the capital city, n = 5) and of a group of Italian children (n = 13) 777:981 We analyzed dietary habits and, by pyrosequencing of the 16S rRNA gene, gut microbiota profiles from fecal samples of children living in a rural village of Burkina Faso (n = 11), of two groups of children living in different urban settings (Nanoro town, n = 8; Ouagadougou, the capital city, n = 5) and of a group of Italian children (n = 13). 29081768 8 92 theme marker 1812:1817 arg1 gene 1819:1822 16S rRNA marker gene 1803:1822 16S rRNA marker gene 1803:1822 Independently of geography and ethnicity, in children living in urban areas these bacterial genera were progressively outcompeted by bacteria more suited to the metabolism of animal protein, fat and sugar rich foods, similarly to Italian children, as resulted by PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States), a predictive functional profiling of microbial communities using 16S rRNA marker gene. 29081768 10 93 theme fast 2284:2287 arg1 globalization 2295:2307 the fast paced globalization 2280:2307 the fast paced globalization of foods 2280:2316 Our results even if in a limited number of individuals point out that dietary habit modifications in the course of urbanization play a role in shaping gut microbiota, and that ancient microorganisms, such as fiber-degrading bacteria, are at risk of being eliminated by the fast paced globalization of foods and by the advent of westernized lifestyle. 29081768 5 94 theme dietary 652:658 arg1 habits 660:665 dietary habits 652:665 dietary habits 652:665 We analyzed dietary habits and, by pyrosequencing of the 16S rRNA gene, gut microbiota profiles from fecal samples of children living in a rural village of Burkina Faso (n = 11), of two groups of children living in different urban settings (Nanoro town, n = 8; Ouagadougou, the capital city, n = 5) and of a group of Italian children (n = 13). 29081768 5 95 theme gene 706:709 arg1 pyrosequencing 675:688 pyrosequencing 675:688 pyrosequencing of the 16S rRNA gene 675:709 We analyzed dietary habits and, by pyrosequencing of the 16S rRNA gene, gut microbiota profiles from fecal samples of children living in a rural village of Burkina Faso (n = 11), of two groups of children living in different urban settings (Nanoro town, n = 8; Ouagadougou, the capital city, n = 5) and of a group of Italian children (n = 13). 29081768 6 96 dep cereals 1126:1132 arg1 changes 1187:1193 changes 1187:1193 changes 1187:1193 We observed that when foods of animal origin, those rich in fat and simple sugars are introduced into a traditional African diet, composed of cereals, legumes and vegetables, the gut microbiota profiles changes. 29081768 8 97 theme fat 1574:1576 arg1 metabolism 1544:1553 the metabolism 1540:1553 the metabolism of animal protein, fat and sugar rich foods 1540:1597 Independently of geography and ethnicity, in children living in urban areas these bacterial genera were progressively outcompeted by bacteria more suited to the metabolism of animal protein, fat and sugar rich foods, similarly to Italian children, as resulted by PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States), a predictive functional profiling of microbial communities using 16S rRNA marker gene. 29081768 5 98 theme = 812:812 arg1 Faso 804:807 Faso 804:807 Faso 804:807 We analyzed dietary habits and, by pyrosequencing of the 16S rRNA gene, gut microbiota profiles from fecal samples of children living in a rural village of Burkina Faso (n = 11), of two groups of children living in different urban settings (Nanoro town, n = 8; Ouagadougou, the capital city, n = 5) and of a group of Italian children (n = 13). 29081768 5 98 theme = 812:812 arg1 n 810:810 n = 11 810:815 n = 11 810:815 We analyzed dietary habits and, by pyrosequencing of the 16S rRNA gene, gut microbiota profiles from fecal samples of children living in a rural village of Burkina Faso (n = 11), of two groups of children living in different urban settings (Nanoro town, n = 8; Ouagadougou, the capital city, n = 5) and of a group of Italian children (n = 13). 29081768 4 99 dep children 494:501 arg1 living 539:544 living 539:544 living in different environments 539:570 Here, we present preliminary observations on the metagenomic scale of microbial changes in small groups of African children belonging to the same ethnicity and living in different environments, compared to children living on the urban area of Florence (Italy). 29081768 4 99 dep children 494:501 arg1 belonging 503:511 belonging 503:511 belonging to the same ethnicity 503:533 Here, we present preliminary observations on the metagenomic scale of microbial changes in small groups of African children belonging to the same ethnicity and living in different environments, compared to children living on the urban area of Florence (Italy). 29081768 10 100 theme shaping 2154:2160 arg1 microbiota 2166:2175 shaping gut microbiota 2154:2175 shaping gut microbiota 2154:2175 Our results even if in a limited number of individuals point out that dietary habit modifications in the course of urbanization play a role in shaping gut microbiota, and that ancient microorganisms, such as fiber-degrading bacteria, are at risk of being eliminated by the fast paced globalization of foods and by the advent of westernized lifestyle. 29081768 4 101 theme African 486:492 arg1 children 494:501 African children 486:501 African children belonging to the same ethnicity and living in different environments 486:570 Here, we present preliminary observations on the metagenomic scale of microbial changes in small groups of African children belonging to the same ethnicity and living in different environments, compared to children living on the urban area of Florence (Italy). 29081768 3 102 theme type 368:371 arg1 diet 373:376 a "globalized" Western type diet 345:376 a "globalized" Western type diet 345:376 When people move from a rural environment to urban areas, and experience improved socio-economic conditions, they are often exposed to a "globalized" Western type diet. 29081768 5 103 theme gut 712:714 arg1 profiles 727:734 gut microbiota profiles 712:734 gut microbiota profiles from fecal samples of children living in a rural village of Burkina Faso (n = 11), of two groups of children living in different urban settings (Nanoro town, n = 8; Ouagadougou, the capital city, n = 5) and of a group of Italian children (n = 13) 712:981 We analyzed dietary habits and, by pyrosequencing of the 16S rRNA gene, gut microbiota profiles from fecal samples of children living in a rural village of Burkina Faso (n = 11), of two groups of children living in different urban settings (Nanoro town, n = 8; Ouagadougou, the capital city, n = 5) and of a group of Italian children (n = 13). 29081768 5 104 theme Italian 957:963 arg1 children 965:972 Italian children 957:972 Italian children 957:972 We analyzed dietary habits and, by pyrosequencing of the 16S rRNA gene, gut microbiota profiles from fecal samples of children living in a rural village of Burkina Faso (n = 11), of two groups of children living in different urban settings (Nanoro town, n = 8; Ouagadougou, the capital city, n = 5) and of a group of Italian children (n = 13). 29081768 8 105 theme sugar 1582:1586 arg1 foods 1593:1597 sugar rich foods 1582:1597 sugar rich foods 1582:1597 Independently of geography and ethnicity, in children living in urban areas these bacterial genera were progressively outcompeted by bacteria more suited to the metabolism of animal protein, fat and sugar rich foods, similarly to Italian children, as resulted by PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States), a predictive functional profiling of microbial communities using 16S rRNA marker gene. 29081768 10 106 theme foods 2312:2316 arg1 globalization 2295:2307 the fast paced globalization 2280:2307 the fast paced globalization of foods 2280:2316 Our results even if in a limited number of individuals point out that dietary habit modifications in the course of urbanization play a role in shaping gut microbiota, and that ancient microorganisms, such as fiber-degrading bacteria, are at risk of being eliminated by the fast paced globalization of foods and by the advent of westernized lifestyle. 29081768 4 107 from groups 476:481 arg1 scale 440:444 the metagenomic scale 424:444 the metagenomic scale of microbial changes in small groups of African children belonging to the same ethnicity and living in different environments 424:570 Here, we present preliminary observations on the metagenomic scale of microbial changes in small groups of African children belonging to the same ethnicity and living in different environments, compared to children living on the urban area of Florence (Italy). 29081768 5 108 theme urban 865:869 arg1 settings 871:878 different urban settings 855:878 different urban settings (Nanoro town, n = 8; Ouagadougou, the capital city, n = 5) 855:937 We analyzed dietary habits and, by pyrosequencing of the 16S rRNA gene, gut microbiota profiles from fecal samples of children living in a rural village of Burkina Faso (n = 11), of two groups of children living in different urban settings (Nanoro town, n = 8; Ouagadougou, the capital city, n = 5) and of a group of Italian children (n = 13). 29081768 5 108 theme urban 865:869 arg1 town 888:891 Nanoro town 881:891 Nanoro town 881:891 We analyzed dietary habits and, by pyrosequencing of the 16S rRNA gene, gut microbiota profiles from fecal samples of children living in a rural village of Burkina Faso (n = 11), of two groups of children living in different urban settings (Nanoro town, n = 8; Ouagadougou, the capital city, n = 5) and of a group of Italian children (n = 13). 29081768 3 109 theme " 358:358 arg1 type 368:371 a "globalized" Western type 345:371 a "globalized" Western type diet 345:376 When people move from a rural environment to urban areas, and experience improved socio-economic conditions, they are often exposed to a "globalized" Western type diet. 29081768 10 110 theme westernized 2339:2349 arg1 lifestyle 2351:2359 westernized lifestyle 2339:2359 westernized lifestyle 2339:2359 Our results even if in a limited number of individuals point out that dietary habit modifications in the course of urbanization play a role in shaping gut microbiota, and that ancient microorganisms, such as fiber-degrading bacteria, are at risk of being eliminated by the fast paced globalization of foods and by the advent of westernized lifestyle. 29081768 5 111 theme 16S 697:699 arg1 gene 706:709 the 16S rRNA gene 693:709 the 16S rRNA gene 693:709 We analyzed dietary habits and, by pyrosequencing of the 16S rRNA gene, gut microbiota profiles from fecal samples of children living in a rural village of Burkina Faso (n = 11), of two groups of children living in different urban settings (Nanoro town, n = 8; Ouagadougou, the capital city, n = 5) and of a group of Italian children (n = 13). 29081768 8 112 theme communities 1785:1795 arg1 profiling 1762:1770 a predictive functional profiling 1738:1770 a predictive functional profiling of microbial communities using 16S rRNA marker gene 1738:1822 Independently of geography and ethnicity, in children living in urban areas these bacterial genera were progressively outcompeted by bacteria more suited to the metabolism of animal protein, fat and sugar rich foods, similarly to Italian children, as resulted by PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States), a predictive functional profiling of microbial communities using 16S rRNA marker gene. 29081768 8 112 theme communities 1785:1795 arg1 PICRUSt 1646:1652 PICRUSt 1646:1652 PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) 1646:1735 Independently of geography and ethnicity, in children living in urban areas these bacterial genera were progressively outcompeted by bacteria more suited to the metabolism of animal protein, fat and sugar rich foods, similarly to Italian children, as resulted by PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States), a predictive functional profiling of microbial communities using 16S rRNA marker gene. 29081768 7 113 from vegetables 1371:1380 arg1 polysaccharides 1350:1364 polysaccharides 1350:1364 polysaccharides from vegetables 1350:1380 Microbiota of rural children retain a geographically unique bacterial reservoir (Prevotella, Treponema, and Succinivibrio), assigned to ferment fiber and polysaccharides from vegetables. 29081768 7 113 from vegetables 1371:1380 arg1 fiber 1340:1344 fiber 1340:1344 fiber 1340:1344 Microbiota of rural children retain a geographically unique bacterial reservoir (Prevotella, Treponema, and Succinivibrio), assigned to ferment fiber and polysaccharides from vegetables. 29081768 5 114 theme group 948:952 arg1 village 785:791 a rural village 777:791 a rural village of Burkina Faso (n = 11), of two groups of children living in different urban settings (Nanoro town, n = 8; Ouagadougou, the capital city, n = 5) and of a group of Italian children (n = 13) 777:981 We analyzed dietary habits and, by pyrosequencing of the 16S rRNA gene, gut microbiota profiles from fecal samples of children living in a rural village of Burkina Faso (n = 11), of two groups of children living in different urban settings (Nanoro town, n = 8; Ouagadougou, the capital city, n = 5) and of a group of Italian children (n = 13). 29081768 7 115 theme bacterial 1256:1264 arg1 reservoir 1266:1274 a geographically unique bacterial reservoir 1232:1274 a geographically unique bacterial reservoir (Prevotella, Treponema, and Succinivibrio) 1232:1317 Microbiota of rural children retain a geographically unique bacterial reservoir (Prevotella, Treponema, and Succinivibrio), assigned to ferment fiber and polysaccharides from vegetables. 29081768 5 116 theme children 836:843 arg1 children 836:843 children 836:843 children living in different urban settings (Nanoro town, n = 8; Ouagadougou, the capital city, n = 5) 836:937 We analyzed dietary habits and, by pyrosequencing of the 16S rRNA gene, gut microbiota profiles from fecal samples of children living in a rural village of Burkina Faso (n = 11), of two groups of children living in different urban settings (Nanoro town, n = 8; Ouagadougou, the capital city, n = 5) and of a group of Italian children (n = 13). 29081768 5 116 theme children 836:843 arg1 groups 826:831 two groups 822:831 two groups of children living in different urban settings (Nanoro town, n = 8; Ouagadougou, the capital city, n = 5) 822:937 We analyzed dietary habits and, by pyrosequencing of the 16S rRNA gene, gut microbiota profiles from fecal samples of children living in a rural village of Burkina Faso (n = 11), of two groups of children living in different urban settings (Nanoro town, n = 8; Ouagadougou, the capital city, n = 5) and of a group of Italian children (n = 13). 29081768 2 117 theme factors 154:160 arg1 factors 154:160 the main factors 145:160 the main factors 145:160 Diet is one of the main factors that affects the composition of gut microbiota. 29081768 2 117 theme factors 154:160 arg1 one 138:140 one 138:140 one 138:140 Diet is one of the main factors that affects the composition of gut microbiota. 29081768 4 118 theme different 549:557 arg1 environments 559:570 different environments 549:570 different environments 549:570 Here, we present preliminary observations on the metagenomic scale of microbial changes in small groups of African children belonging to the same ethnicity and living in different environments, compared to children living on the urban area of Florence (Italy). 29081768 6 119 theme microbiota 1167:1176 arg1 profiles 1178:1185 the gut microbiota profiles 1159:1185 the gut microbiota profiles 1159:1185 We observed that when foods of animal origin, those rich in fat and simple sugars are introduced into a traditional African diet, composed of cereals, legumes and vegetables, the gut microbiota profiles changes. 29081768 6 119 theme microbiota 1167:1176 arg1 vegetables 1147:1156 vegetables 1147:1156 vegetables 1147:1156 We observed that when foods of animal origin, those rich in fat and simple sugars are introduced into a traditional African diet, composed of cereals, legumes and vegetables, the gut microbiota profiles changes. 29081768 1 120 from Investigation 54:66 arg1 Children 71:78 Children 71:78 Children 71:78 A Preliminary Investigation in Children Living in Rural and Urban Burkina Faso and Italy. 27216447 7 0 theme rRNA 850:853 arg1 sequences 860:868 16S rRNA gene sequences 846:868 16S rRNA gene sequences of strain MBL-TLPT and relatives 846:901 Phylogenetic analysis of 16S rRNA gene sequences of strain MBL-TLPT and relatives showed its affiliation to the genus Tepidibacillus. 27216447 1 1 theme emended 146:152 arg1 description 154:164 emended description 146:164 emended description 146:164 nov., a moderately thermophilic, selenate- and arsenate-respiring hydrolytic bacterium isolated from a gold mine, and emended description of the genus Tepidibacillus. 27216447 8 2 theme % 1018:1018 arg1 identity 1020:1027 97.1 % identity 1013:1027 97.1 % identity of 16S rRNA gene sequences 1013:1054 Tepidibacillus fermentans STGHT was its closest relative (97.1 % identity of 16S rRNA gene sequences). 27216447 3 3 from rods 477:480 arg1 length 519:524 length 519:524 length 519:524 Cells of the new isolate were flagellated, spore-forming rods, 0.25-0.5 µm in width and 3-15 µm in length. 27216447 3 3 from rods 477:480 arg1 width 498:502 width 498:502 width 498:502 Cells of the new isolate were flagellated, spore-forming rods, 0.25-0.5 µm in width and 3-15 µm in length. 27216447 8 4 theme 16S 1032:1034 arg1 sequences 1046:1054 16S rRNA gene sequences 1032:1054 16S rRNA gene sequences 1032:1054 Tepidibacillus fermentans STGHT was its closest relative (97.1 % identity of 16S rRNA gene sequences). 27216447 9 5 theme novel 1157:1161 arg1 sp 1196:1197 Tepidibacillus infernus sp 1172:1197 Tepidibacillus infernus sp 1172:1197 Based on phylogenetic analysis and the physiological properties of the novel isolate, we propose a novel species, Tepidibacillus infernus sp. 27216447 9 5 theme novel 1157:1161 arg1 species 1163:1169 a novel species 1155:1169 a novel species 1155:1169 Based on phylogenetic analysis and the physiological properties of the novel isolate, we propose a novel species, Tepidibacillus infernus sp. 27216447 10 6 theme 28123T=VKM 1225:1234 arg1 MBL-TLPT 1211:1218 MBL-TLPT 1211:1218 MBL-TLPT(=DSM 28123T=VKM В-2949T) 1211:1243 nov., with MBL-TLPT(=DSM 28123T=VKM В-2949T) as the type strain. 27216447 10 6 theme 28123T=VKM 1225:1234 arg1 В-2949T 1236:1242 =DSM 28123T=VKM В-2949T 1220:1242 =DSM 28123T=VKM В-2949T 1220:1242 nov., with MBL-TLPT(=DSM 28123T=VKM В-2949T) as the type strain. 27216447 1 7 theme thermophilic 47:58 arg1 bacterium 105:113 a moderately thermophilic, selenate- and arsenate-respiring hydrolytic bacterium 34:113 a moderately thermophilic, selenate- and arsenate-respiring hydrolytic bacterium isolated from a gold mine, and emended description of the genus Tepidibacillus 34:192 nov., a moderately thermophilic, selenate- and arsenate-respiring hydrolytic bacterium isolated from a gold mine, and emended description of the genus Tepidibacillus. 27216447 1 7 theme thermophilic 47:58 arg1 nov. 28:31 nov. 28:31 nov. 28:31 nov., a moderately thermophilic, selenate- and arsenate-respiring hydrolytic bacterium isolated from a gold mine, and emended description of the genus Tepidibacillus. 27216447 10 8 theme =DSM 1220:1223 arg1 MBL-TLPT 1211:1218 MBL-TLPT 1211:1218 MBL-TLPT(=DSM 28123T=VKM В-2949T) 1211:1243 nov., with MBL-TLPT(=DSM 28123T=VKM В-2949T) as the type strain. 27216447 10 8 theme =DSM 1220:1223 arg1 В-2949T 1236:1242 =DSM 28123T=VKM В-2949T 1220:1242 =DSM 28123T=VKM В-2949T 1220:1242 nov., with MBL-TLPT(=DSM 28123T=VKM В-2949T) as the type strain. 27216447 6 9 theme G+C 785:787 arg1 % 818:818 35 mol% 812:818 35 mol% 812:818 The G+C content of the DNA was 35 mol%. 27216447 6 9 theme G+C 785:787 arg1 content 789:795 The G+C content 781:795 The G+C content of the DNA 781:806 The G+C content of the DNA was 35 mol%. 27216447 3 10 dep flagellated 450:460 arg1 spore-forming 463:475 spore-forming 463:475 spore-forming 463:475 Cells of the new isolate were flagellated, spore-forming rods, 0.25-0.5 µm in width and 3-15 µm in length. 27216447 10 11 dep MBL-TLPT 1211:1218 arg1 strain 1257:1262 the type strain 1248:1262 the type strain 1248:1262 nov., with MBL-TLPT(=DSM 28123T=VKM В-2949T) as the type strain. 27216447 8 12 theme gene 1041:1044 arg1 sequences 1046:1054 16S rRNA gene sequences 1032:1054 16S rRNA gene sequences 1032:1054 Tepidibacillus fermentans STGHT was its closest relative (97.1 % identity of 16S rRNA gene sequences). 27216447 3 13 theme isolate 437:443 arg1 Cells 420:424 Cells 420:424 Cells of the new isolate 420:443 Cells of the new isolate were flagellated, spore-forming rods, 0.25-0.5 µm in width and 3-15 µm in length. 27216447 1 14 theme selenate- 61:69 arg1 bacterium 105:113 a moderately thermophilic, selenate- and arsenate-respiring hydrolytic bacterium 34:113 a moderately thermophilic, selenate- and arsenate-respiring hydrolytic bacterium isolated from a gold mine, and emended description of the genus Tepidibacillus 34:192 nov., a moderately thermophilic, selenate- and arsenate-respiring hydrolytic bacterium isolated from a gold mine, and emended description of the genus Tepidibacillus. 27216447 1 14 theme selenate- 61:69 arg1 nov. 28:31 nov. 28:31 nov. 28:31 nov., a moderately thermophilic, selenate- and arsenate-respiring hydrolytic bacterium isolated from a gold mine, and emended description of the genus Tepidibacillus. 27216447 1 15 theme genus 173:177 arg1 Tepidibacillus 179:192 the genus Tepidibacillus 169:192 the genus Tepidibacillus 169:192 nov., a moderately thermophilic, selenate- and arsenate-respiring hydrolytic bacterium isolated from a gold mine, and emended description of the genus Tepidibacillus. 27216447 4 16 dep g 655:655 arg1 l-1 657:659 l-1 657:659 0 to 85 g l-1 647:659 Strain MBL-TLPT grew in the temperature range from 25 to 58 °C, pH range from 5.6 to 8.8 and at NaCl concentration from 0 to 85 g l-1. 27216447 9 17 theme Tepidibacillus 1172:1185 arg1 sp 1196:1197 Tepidibacillus infernus sp 1172:1197 Tepidibacillus infernus sp 1172:1197 Based on phylogenetic analysis and the physiological properties of the novel isolate, we propose a novel species, Tepidibacillus infernus sp. 27216447 9 17 theme Tepidibacillus 1172:1185 arg1 species 1163:1169 a novel species 1155:1169 a novel species 1155:1169 Based on phylogenetic analysis and the physiological properties of the novel isolate, we propose a novel species, Tepidibacillus infernus sp. 27216447 9 18 theme phylogenetic 1067:1078 arg1 analysis 1080:1087 phylogenetic analysis 1067:1087 phylogenetic analysis 1067:1087 Based on phylogenetic analysis and the physiological properties of the novel isolate, we propose a novel species, Tepidibacillus infernus sp. 27216447 8 19 theme sequences 1046:1054 arg1 identity 1020:1027 97.1 % identity 1013:1027 97.1 % identity of 16S rRNA gene sequences 1013:1054 Tepidibacillus fermentans STGHT was its closest relative (97.1 % identity of 16S rRNA gene sequences). 27216447 2 20 theme water 378:382 arg1 flow 359:362 the flow 355:362 the flow of subsurface water in TauTona gold mine, South Africa 355:417 A novel aerotolerant anaerobic, moderately thermophilic, organotrophic bacterium, strain MBL-TLPT, was isolated from a sample of microbial mat, developed under the flow of subsurface water in TauTona gold mine, South Africa. 27216447 0 21 theme infernus 15:22 arg1 sp 24:25 Tepidibacillus infernus sp 0:25 Tepidibacillus infernus sp. 0:26 Tepidibacillus infernus sp. 27216447 9 22 theme infernus 1187:1194 arg1 sp 1196:1197 Tepidibacillus infernus sp 1172:1197 Tepidibacillus infernus sp 1172:1197 Based on phylogenetic analysis and the physiological properties of the novel isolate, we propose a novel species, Tepidibacillus infernus sp. 27216447 9 22 theme infernus 1187:1194 arg1 species 1163:1169 a novel species 1155:1169 a novel species 1155:1169 Based on phylogenetic analysis and the physiological properties of the novel isolate, we propose a novel species, Tepidibacillus infernus sp. 27216447 4 23 from g 655:655 arg1 concentration 628:640 NaCl concentration 623:640 NaCl concentration from 0 to 85 g l-1 623:659 Strain MBL-TLPT grew in the temperature range from 25 to 58 °C, pH range from 5.6 to 8.8 and at NaCl concentration from 0 to 85 g l-1. 27216447 1 24 theme arsenate-respiring 75:92 arg1 bacterium 105:113 a moderately thermophilic, selenate- and arsenate-respiring hydrolytic bacterium 34:113 a moderately thermophilic, selenate- and arsenate-respiring hydrolytic bacterium isolated from a gold mine, and emended description of the genus Tepidibacillus 34:192 nov., a moderately thermophilic, selenate- and arsenate-respiring hydrolytic bacterium isolated from a gold mine, and emended description of the genus Tepidibacillus. 27216447 1 24 theme arsenate-respiring 75:92 arg1 nov. 28:31 nov. 28:31 nov. 28:31 nov., a moderately thermophilic, selenate- and arsenate-respiring hydrolytic bacterium isolated from a gold mine, and emended description of the genus Tepidibacillus. 27216447 2 25 theme subsurface 367:376 arg1 water 378:382 subsurface water 367:382 subsurface water 367:382 A novel aerotolerant anaerobic, moderately thermophilic, organotrophic bacterium, strain MBL-TLPT, was isolated from a sample of microbial mat, developed under the flow of subsurface water in TauTona gold mine, South Africa. 27216447 0 26 theme Tepidibacillus 0:13 arg1 sp 24:25 Tepidibacillus infernus sp 0:25 Tepidibacillus infernus sp. 0:26 Tepidibacillus infernus sp. 27216447 4 27 dep 85 652:653 arg1 to 649:650 to 649:650 to 649:650 Strain MBL-TLPT grew in the temperature range from 25 to 58 °C, pH range from 5.6 to 8.8 and at NaCl concentration from 0 to 85 g l-1. 27216447 2 28 from flow 359:362 arg1 South 406:410 South 406:410 South 406:410 A novel aerotolerant anaerobic, moderately thermophilic, organotrophic bacterium, strain MBL-TLPT, was isolated from a sample of microbial mat, developed under the flow of subsurface water in TauTona gold mine, South Africa. 27216447 2 28 from flow 359:362 arg1 Africa 412:417 Africa 412:417 Africa 412:417 A novel aerotolerant anaerobic, moderately thermophilic, organotrophic bacterium, strain MBL-TLPT, was isolated from a sample of microbial mat, developed under the flow of subsurface water in TauTona gold mine, South Africa. 27216447 1 29 theme hydrolytic 94:103 arg1 bacterium 105:113 a moderately thermophilic, selenate- and arsenate-respiring hydrolytic bacterium 34:113 a moderately thermophilic, selenate- and arsenate-respiring hydrolytic bacterium isolated from a gold mine, and emended description of the genus Tepidibacillus 34:192 nov., a moderately thermophilic, selenate- and arsenate-respiring hydrolytic bacterium isolated from a gold mine, and emended description of the genus Tepidibacillus. 27216447 1 29 theme hydrolytic 94:103 arg1 nov. 28:31 nov. 28:31 nov. 28:31 nov., a moderately thermophilic, selenate- and arsenate-respiring hydrolytic bacterium isolated from a gold mine, and emended description of the genus Tepidibacillus. 27216447 1 30 theme Tepidibacillus 179:192 arg1 mine 136:139 a gold mine 129:139 a gold mine 129:139 nov., a moderately thermophilic, selenate- and arsenate-respiring hydrolytic bacterium isolated from a gold mine, and emended description of the genus Tepidibacillus. 27216447 1 30 theme Tepidibacillus 179:192 arg1 description 154:164 emended description 146:164 emended description 146:164 nov., a moderately thermophilic, selenate- and arsenate-respiring hydrolytic bacterium isolated from a gold mine, and emended description of the genus Tepidibacillus. 27216447 10 31 theme type 1252:1255 arg1 strain 1257:1262 the type strain 1248:1262 the type strain 1248:1262 nov., with MBL-TLPT(=DSM 28123T=VKM В-2949T) as the type strain. 27216447 7 32 theme genus 933:937 arg1 Tepidibacillus 939:952 the genus Tepidibacillus 929:952 the genus Tepidibacillus 929:952 Phylogenetic analysis of 16S rRNA gene sequences of strain MBL-TLPT and relatives showed its affiliation to the genus Tepidibacillus. 27216447 3 33 from µm 492:493 arg1 length 519:524 length 519:524 length 519:524 Cells of the new isolate were flagellated, spore-forming rods, 0.25-0.5 µm in width and 3-15 µm in length. 27216447 3 33 from µm 492:493 arg1 width 498:502 width 498:502 width 498:502 Cells of the new isolate were flagellated, spore-forming rods, 0.25-0.5 µm in width and 3-15 µm in length. 27216447 4 34 from 58 °C 584:588 arg1 range 567:571 the temperature range 551:571 the temperature range from 25 to 58 °C, pH range from 5.6 to 8.8 551:614 Strain MBL-TLPT grew in the temperature range from 25 to 58 °C, pH range from 5.6 to 8.8 and at NaCl concentration from 0 to 85 g l-1. 27216447 3 35 theme new 433:435 arg1 isolate 437:443 the new isolate 429:443 the new isolate 429:443 Cells of the new isolate were flagellated, spore-forming rods, 0.25-0.5 µm in width and 3-15 µm in length. 27216447 4 36 dep 8.8 612:614 arg1 to 609:610 to 609:610 to 609:610 Strain MBL-TLPT grew in the temperature range from 25 to 58 °C, pH range from 5.6 to 8.8 and at NaCl concentration from 0 to 85 g l-1. 27216447 10 37 dep nov. 1200:1203 arg1 with 1206:1209 with 1206:1209 with 1206:1209 nov., with MBL-TLPT(=DSM 28123T=VKM В-2949T) as the type strain. 27216447 7 38 theme Phylogenetic 821:832 arg1 analysis 834:841 Phylogenetic analysis 821:841 Phylogenetic analysis of 16S rRNA gene sequences of strain MBL-TLPT and relatives 821:901 Phylogenetic analysis of 16S rRNA gene sequences of strain MBL-TLPT and relatives showed its affiliation to the genus Tepidibacillus. 27216447 2 39 dep anaerobic 216:224 arg1 thermophilic 238:249 thermophilic 238:249 thermophilic 238:249 A novel aerotolerant anaerobic, moderately thermophilic, organotrophic bacterium, strain MBL-TLPT, was isolated from a sample of microbial mat, developed under the flow of subsurface water in TauTona gold mine, South Africa. 27216447 2 40 dep isolated 298:305 arg1 developed 339:347 developed 339:347 developed under the flow of subsurface water in TauTona gold mine, South Africa 339:417 A novel aerotolerant anaerobic, moderately thermophilic, organotrophic bacterium, strain MBL-TLPT, was isolated from a sample of microbial mat, developed under the flow of subsurface water in TauTona gold mine, South Africa. 27216447 9 41 theme physiological 1097:1109 arg1 properties 1111:1120 the physiological properties 1093:1120 the physiological properties of the novel isolate 1093:1141 Based on phylogenetic analysis and the physiological properties of the novel isolate, we propose a novel species, Tepidibacillus infernus sp. 27216447 5 42 theme xanthan 768:774 arg1 gum 776:778 xanthan gum 768:778 xanthan gum 768:778 The isolate was able to ferment yeast extract and mono-, oligo- and polysaccharides, including starch and xanthan gum. 27216447 8 43 theme fermentans 970:979 arg1 STGHT 981:985 Tepidibacillus fermentans STGHT 955:985 Tepidibacillus fermentans STGHT 955:985 Tepidibacillus fermentans STGHT was its closest relative (97.1 % identity of 16S rRNA gene sequences). 27216447 4 44 dep 58 °C 584:588 arg1 to 581:582 to 581:582 to 581:582 Strain MBL-TLPT grew in the temperature range from 25 to 58 °C, pH range from 5.6 to 8.8 and at NaCl concentration from 0 to 85 g l-1. 27216447 7 45 theme MBL-TLPT 880:887 arg1 sequences 860:868 16S rRNA gene sequences 846:868 16S rRNA gene sequences of strain MBL-TLPT and relatives 846:901 Phylogenetic analysis of 16S rRNA gene sequences of strain MBL-TLPT and relatives showed its affiliation to the genus Tepidibacillus. 27216447 8 46 theme rRNA 1036:1039 arg1 sequences 1046:1054 16S rRNA gene sequences 1032:1054 16S rRNA gene sequences 1032:1054 Tepidibacillus fermentans STGHT was its closest relative (97.1 % identity of 16S rRNA gene sequences). 27216447 6 47 theme mol 815:817 arg1 % 818:818 35 mol% 812:818 35 mol% 812:818 The G+C content of the DNA was 35 mol%. 27216447 6 47 theme mol 815:817 arg1 content 789:795 The G+C content 781:795 The G+C content of the DNA 781:806 The G+C content of the DNA was 35 mol%. 27216447 5 48 theme yeast 694:698 arg1 polysaccharides 730:744 polysaccharides 730:744 polysaccharides 730:744 The isolate was able to ferment yeast extract and mono-, oligo- and polysaccharides, including starch and xanthan gum. 27216447 5 48 theme yeast 694:698 arg1 oligo- 719:724 oligo- 719:724 oligo- 719:724 The isolate was able to ferment yeast extract and mono-, oligo- and polysaccharides, including starch and xanthan gum. 27216447 5 48 theme yeast 694:698 arg1 extract 700:706 yeast extract 694:706 yeast extract 694:706 The isolate was able to ferment yeast extract and mono-, oligo- and polysaccharides, including starch and xanthan gum. 27216447 1 49 attach isolated 115:122 arg2 bacterium 105:113 a moderately thermophilic, selenate- and arsenate-respiring hydrolytic bacterium 34:113 a moderately thermophilic, selenate- and arsenate-respiring hydrolytic bacterium isolated from a gold mine, and emended description of the genus Tepidibacillus 34:192 nov., a moderately thermophilic, selenate- and arsenate-respiring hydrolytic bacterium isolated from a gold mine, and emended description of the genus Tepidibacillus. 27216447 1 49 attach isolated 115:122 arg1 description 154:164 emended description 146:164 emended description 146:164 nov., a moderately thermophilic, selenate- and arsenate-respiring hydrolytic bacterium isolated from a gold mine, and emended description of the genus Tepidibacillus. 27216447 1 49 attach isolated 115:122 arg2 nov. 28:31 nov. 28:31 nov. 28:31 nov., a moderately thermophilic, selenate- and arsenate-respiring hydrolytic bacterium isolated from a gold mine, and emended description of the genus Tepidibacillus. 27216447 1 49 attach isolated 115:122 arg1 mine 136:139 a gold mine 129:139 a gold mine 129:139 nov., a moderately thermophilic, selenate- and arsenate-respiring hydrolytic bacterium isolated from a gold mine, and emended description of the genus Tepidibacillus. 27216447 8 50 theme Tepidibacillus 955:968 arg1 STGHT 981:985 Tepidibacillus fermentans STGHT 955:985 Tepidibacillus fermentans STGHT 955:985 Tepidibacillus fermentans STGHT was its closest relative (97.1 % identity of 16S rRNA gene sequences). 27216447 2 51 theme aerotolerant 203:214 arg1 strain 277:282 strain MBL-TLPT 277:291 strain MBL-TLPT 277:291 A novel aerotolerant anaerobic, moderately thermophilic, organotrophic bacterium, strain MBL-TLPT, was isolated from a sample of microbial mat, developed under the flow of subsurface water in TauTona gold mine, South Africa. 27216447 2 51 theme aerotolerant 203:214 arg1 bacterium 266:274 A novel aerotolerant anaerobic, moderately thermophilic, organotrophic bacterium 195:274 A novel aerotolerant anaerobic, moderately thermophilic, organotrophic bacterium 195:274 A novel aerotolerant anaerobic, moderately thermophilic, organotrophic bacterium, strain MBL-TLPT, was isolated from a sample of microbial mat, developed under the flow of subsurface water in TauTona gold mine, South Africa. 27216447 2 52 theme anaerobic 216:224 arg1 strain 277:282 strain MBL-TLPT 277:291 strain MBL-TLPT 277:291 A novel aerotolerant anaerobic, moderately thermophilic, organotrophic bacterium, strain MBL-TLPT, was isolated from a sample of microbial mat, developed under the flow of subsurface water in TauTona gold mine, South Africa. 27216447 2 52 theme anaerobic 216:224 arg1 bacterium 266:274 A novel aerotolerant anaerobic, moderately thermophilic, organotrophic bacterium 195:274 A novel aerotolerant anaerobic, moderately thermophilic, organotrophic bacterium 195:274 A novel aerotolerant anaerobic, moderately thermophilic, organotrophic bacterium, strain MBL-TLPT, was isolated from a sample of microbial mat, developed under the flow of subsurface water in TauTona gold mine, South Africa. 27216447 2 53 theme mat 334:336 arg1 sample 314:319 a sample 312:319 a sample of microbial mat 312:336 A novel aerotolerant anaerobic, moderately thermophilic, organotrophic bacterium, strain MBL-TLPT, was isolated from a sample of microbial mat, developed under the flow of subsurface water in TauTona gold mine, South Africa. 27216447 3 54 from µm 513:514 arg1 length 519:524 length 519:524 length 519:524 Cells of the new isolate were flagellated, spore-forming rods, 0.25-0.5 µm in width and 3-15 µm in length. 27216447 3 54 from µm 513:514 arg1 width 498:502 width 498:502 width 498:502 Cells of the new isolate were flagellated, spore-forming rods, 0.25-0.5 µm in width and 3-15 µm in length. 27216447 7 55 theme relatives 893:901 arg1 sequences 860:868 16S rRNA gene sequences 846:868 16S rRNA gene sequences of strain MBL-TLPT and relatives 846:901 Phylogenetic analysis of 16S rRNA gene sequences of strain MBL-TLPT and relatives showed its affiliation to the genus Tepidibacillus. 27216447 2 56 theme novel 197:201 arg1 strain 277:282 strain MBL-TLPT 277:291 strain MBL-TLPT 277:291 A novel aerotolerant anaerobic, moderately thermophilic, organotrophic bacterium, strain MBL-TLPT, was isolated from a sample of microbial mat, developed under the flow of subsurface water in TauTona gold mine, South Africa. 27216447 2 56 theme novel 197:201 arg1 bacterium 266:274 A novel aerotolerant anaerobic, moderately thermophilic, organotrophic bacterium 195:274 A novel aerotolerant anaerobic, moderately thermophilic, organotrophic bacterium 195:274 A novel aerotolerant anaerobic, moderately thermophilic, organotrophic bacterium, strain MBL-TLPT, was isolated from a sample of microbial mat, developed under the flow of subsurface water in TauTona gold mine, South Africa. 27216447 7 57 theme strain 873:878 arg1 MBL-TLPT 880:887 strain MBL-TLPT 873:887 strain MBL-TLPT 873:887 Phylogenetic analysis of 16S rRNA gene sequences of strain MBL-TLPT and relatives showed its affiliation to the genus Tepidibacillus. 27216447 1 58 theme gold 131:134 arg1 mine 136:139 a gold mine 129:139 a gold mine 129:139 nov., a moderately thermophilic, selenate- and arsenate-respiring hydrolytic bacterium isolated from a gold mine, and emended description of the genus Tepidibacillus. 27216447 4 59 theme temperature 555:565 arg1 range 567:571 the temperature range 551:571 the temperature range from 25 to 58 °C, pH range from 5.6 to 8.8 551:614 Strain MBL-TLPT grew in the temperature range from 25 to 58 °C, pH range from 5.6 to 8.8 and at NaCl concentration from 0 to 85 g l-1. 27216447 8 60 theme closest 995:1001 arg1 relative 1003:1010 its closest relative 991:1010 its closest relative (97.1 % identity of 16S rRNA gene sequences) 991:1055 Tepidibacillus fermentans STGHT was its closest relative (97.1 % identity of 16S rRNA gene sequences). 27216447 9 61 theme isolate 1135:1141 arg1 properties 1111:1120 the physiological properties 1093:1120 the physiological properties of the novel isolate 1093:1141 Based on phylogenetic analysis and the physiological properties of the novel isolate, we propose a novel species, Tepidibacillus infernus sp. 27216447 9 61 theme isolate 1135:1141 arg1 analysis 1080:1087 phylogenetic analysis 1067:1087 phylogenetic analysis 1067:1087 Based on phylogenetic analysis and the physiological properties of the novel isolate, we propose a novel species, Tepidibacillus infernus sp. 27216447 7 62 theme gene 855:858 arg1 sequences 860:868 16S rRNA gene sequences 846:868 16S rRNA gene sequences of strain MBL-TLPT and relatives 846:901 Phylogenetic analysis of 16S rRNA gene sequences of strain MBL-TLPT and relatives showed its affiliation to the genus Tepidibacillus. 27216447 3 63 theme flagellated 450:460 arg1 rods 477:480 flagellated, spore-forming rods 450:480 flagellated, spore-forming rods 450:480 Cells of the new isolate were flagellated, spore-forming rods, 0.25-0.5 µm in width and 3-15 µm in length. 27216447 2 64 theme microbial 324:332 arg1 mat 334:336 microbial mat 324:336 microbial mat 324:336 A novel aerotolerant anaerobic, moderately thermophilic, organotrophic bacterium, strain MBL-TLPT, was isolated from a sample of microbial mat, developed under the flow of subsurface water in TauTona gold mine, South Africa. 27216447 8 65 theme 97.1  1013:1017 arg1 % 1018:1018 % 1018:1018 % 1018:1018 Tepidibacillus fermentans STGHT was its closest relative (97.1 % identity of 16S rRNA gene sequences). 27216447 2 66 theme organotrophic 252:264 arg1 strain 277:282 strain MBL-TLPT 277:291 strain MBL-TLPT 277:291 A novel aerotolerant anaerobic, moderately thermophilic, organotrophic bacterium, strain MBL-TLPT, was isolated from a sample of microbial mat, developed under the flow of subsurface water in TauTona gold mine, South Africa. 27216447 2 66 theme organotrophic 252:264 arg1 bacterium 266:274 A novel aerotolerant anaerobic, moderately thermophilic, organotrophic bacterium 195:274 A novel aerotolerant anaerobic, moderately thermophilic, organotrophic bacterium 195:274 A novel aerotolerant anaerobic, moderately thermophilic, organotrophic bacterium, strain MBL-TLPT, was isolated from a sample of microbial mat, developed under the flow of subsurface water in TauTona gold mine, South Africa. 27216447 7 67 theme sequences 860:868 arg1 analysis 834:841 Phylogenetic analysis 821:841 Phylogenetic analysis of 16S rRNA gene sequences of strain MBL-TLPT and relatives 821:901 Phylogenetic analysis of 16S rRNA gene sequences of strain MBL-TLPT and relatives showed its affiliation to the genus Tepidibacillus. 27216447 9 68 theme novel 1129:1133 arg1 isolate 1135:1141 the novel isolate 1125:1141 the novel isolate 1125:1141 Based on phylogenetic analysis and the physiological properties of the novel isolate, we propose a novel species, Tepidibacillus infernus sp. 27216447 4 69 theme pH 591:592 arg1 58 °C 584:588 58 °C 584:588 58 °C 584:588 Strain MBL-TLPT grew in the temperature range from 25 to 58 °C, pH range from 5.6 to 8.8 and at NaCl concentration from 0 to 85 g l-1. 27216447 4 69 theme pH 591:592 arg1 range 594:598 pH range 591:598 pH range 591:598 Strain MBL-TLPT grew in the temperature range from 25 to 58 °C, pH range from 5.6 to 8.8 and at NaCl concentration from 0 to 85 g l-1. 27216447 6 70 theme DNA 804:806 arg1 % 818:818 35 mol% 812:818 35 mol% 812:818 The G+C content of the DNA was 35 mol%. 27216447 6 70 theme DNA 804:806 arg1 content 789:795 The G+C content 781:795 The G+C content of the DNA 781:806 The G+C content of the DNA was 35 mol%. 27216447 7 71 theme 16S 846:848 arg1 sequences 860:868 16S rRNA gene sequences 846:868 16S rRNA gene sequences of strain MBL-TLPT and relatives 846:901 Phylogenetic analysis of 16S rRNA gene sequences of strain MBL-TLPT and relatives showed its affiliation to the genus Tepidibacillus. 27216447 8 72 dep relative 1003:1010 arg1 identity 1020:1027 97.1 % identity 1013:1027 97.1 % identity of 16S rRNA gene sequences 1013:1054 Tepidibacillus fermentans STGHT was its closest relative (97.1 % identity of 16S rRNA gene sequences). 27216447 4 73 theme NaCl 623:626 arg1 concentration 628:640 NaCl concentration 623:640 NaCl concentration from 0 to 85 g l-1 623:659 Strain MBL-TLPT grew in the temperature range from 25 to 58 °C, pH range from 5.6 to 8.8 and at NaCl concentration from 0 to 85 g l-1. 27026397 7 0 theme [1.55 1134:1138 arg1 Å 1140:1140 the presence [1.55 Å 1121:1140 the presence [1.55 Å (1 Å=0.1 nm) 1121:1153 We have identified a carbohydrate esterase family 1 (CE1) ferulic acid esterase (FAE) belonging to Anaeromyces mucronatus(AmCE1/Fae1a), and determined its X-ray structure in both the presence [1.55 Å (1 Å=0.1 nm)] and absence (1.60 Å) of ferulic acid. 27026397 7 0 theme [1.55 1134:1138 arg1 Å 1174:1174 1.60 Å 1169:1174 1.60 Å 1169:1174 We have identified a carbohydrate esterase family 1 (CE1) ferulic acid esterase (FAE) belonging to Anaeromyces mucronatus(AmCE1/Fae1a), and determined its X-ray structure in both the presence [1.55 Å (1 Å=0.1 nm)] and absence (1.60 Å) of ferulic acid. 27026397 7 0 theme [1.55 1134:1138 arg1 nm 1151:1152 1 Å=0.1 nm 1143:1152 1 Å=0.1 nm 1143:1152 We have identified a carbohydrate esterase family 1 (CE1) ferulic acid esterase (FAE) belonging to Anaeromyces mucronatus(AmCE1/Fae1a), and determined its X-ray structure in both the presence [1.55 Å (1 Å=0.1 nm)] and absence (1.60 Å) of ferulic acid. 27026397 7 1 theme presence 1125:1132 arg1 Å 1140:1140 the presence [1.55 Å 1121:1140 the presence [1.55 Å (1 Å=0.1 nm) 1121:1153 We have identified a carbohydrate esterase family 1 (CE1) ferulic acid esterase (FAE) belonging to Anaeromyces mucronatus(AmCE1/Fae1a), and determined its X-ray structure in both the presence [1.55 Å (1 Å=0.1 nm)] and absence (1.60 Å) of ferulic acid. 27026397 7 1 theme presence 1125:1132 arg1 Å 1174:1174 1.60 Å 1169:1174 1.60 Å 1169:1174 We have identified a carbohydrate esterase family 1 (CE1) ferulic acid esterase (FAE) belonging to Anaeromyces mucronatus(AmCE1/Fae1a), and determined its X-ray structure in both the presence [1.55 Å (1 Å=0.1 nm)] and absence (1.60 Å) of ferulic acid. 27026397 7 1 theme presence 1125:1132 arg1 nm 1151:1152 1 Å=0.1 nm 1143:1152 1 Å=0.1 nm 1143:1152 We have identified a carbohydrate esterase family 1 (CE1) ferulic acid esterase (FAE) belonging to Anaeromyces mucronatus(AmCE1/Fae1a), and determined its X-ray structure in both the presence [1.55 Å (1 Å=0.1 nm)] and absence (1.60 Å) of ferulic acid. 27026397 5 2 theme anaerobic 636:644 arg1 fungi 646:650 The anaerobic fungi 632:650 The anaerobic fungi (phylum Neocallimastigomycota) 632:681 The anaerobic fungi (phylum Neocallimastigomycota) are key members of this ecosystem that express a large repertoire of carbohydrate-active enzymes (CAZymes) with little sequence identity with characterized CAZymes [Lombard, Golaconda, Drula, Coutinho and Henrissat (2014) Nucleic Acids Res. 27026397 5 2 theme anaerobic 636:644 arg1 Neocallimastigomycota 660:680 phylum Neocallimastigomycota 653:680 phylum Neocallimastigomycota 653:680 The anaerobic fungi (phylum Neocallimastigomycota) are key members of this ecosystem that express a large repertoire of carbohydrate-active enzymes (CAZymes) with little sequence identity with characterized CAZymes [Lombard, Golaconda, Drula, Coutinho and Henrissat (2014) Nucleic Acids Res. 27026397 5 2 theme anaerobic 636:644 arg1 members 691:697 key members 687:697 key members of this ecosystem that express a large repertoire of carbohydrate-active enzymes (CAZymes) with little sequence identity with characterized CAZymes [Lombard, Golaconda, Drula, Coutinho and Henrissat (2014) Nucleic Acids Res 687:921 The anaerobic fungi (phylum Neocallimastigomycota) are key members of this ecosystem that express a large repertoire of carbohydrate-active enzymes (CAZymes) with little sequence identity with characterized CAZymes [Lombard, Golaconda, Drula, Coutinho and Henrissat (2014) Nucleic Acids Res. 27026397 11 3 from basis 1824:1828 arg1 FAEs 1856:1859 FAEs 1856:1859 FAEs 1856:1859 Based on comparisons to structurally characterized FAEs, we propose that the β-clamp may define the structural basis of exolytic activities in FAEs. 27026397 13 4 with bioconversion 2021:2033 arg1 variations 2051:2060 variations 2051:2060 variations in cell wall composition 2051:2085 These insights hold promise for rationally identifying enzymes tailored for bioconversion of biomass with variations in cell wall composition. 27026397 4 5 from ability 554:560 arg1 unique 538:543 unique 538:543 unique 538:543 Ruminant livestock are unique in their ability to degrade lignocellulose through the action of their gut microbiome. 27026397 7 6 theme X-ray 1097:1101 arg1 structure 1103:1111 its X-ray structure 1093:1111 its X-ray structure in both the presence [1.55 Å (1 Å=0.1 nm)] and absence (1.60 Å) of ferulic acid 1093:1191 We have identified a carbohydrate esterase family 1 (CE1) ferulic acid esterase (FAE) belonging to Anaeromyces mucronatus(AmCE1/Fae1a), and determined its X-ray structure in both the presence [1.55 Å (1 Å=0.1 nm)] and absence (1.60 Å) of ferulic acid. 27026397 2 7 theme lignocellulose 311:324 arg1 turnover 299:306 the biocatalytic turnover 282:306 the biocatalytic turnover of lignocellulose 282:324 Major obstacles in the biocatalytic turnover of lignocellulose are ester-linked decorations that prevent access to primary structural polysaccharides. 27026397 5 8 dep CAZymes 839:845 arg1 [Lombard 847:854 [Lombard 847:854 [Lombard 847:854 The anaerobic fungi (phylum Neocallimastigomycota) are key members of this ecosystem that express a large repertoire of carbohydrate-active enzymes (CAZymes) with little sequence identity with characterized CAZymes [Lombard, Golaconda, Drula, Coutinho and Henrissat (2014) Nucleic Acids Res. 27026397 0 9 theme acid 114:117 arg1 esterases 119:127 ferulic acid esterases 106:127 ferulic acid esterases 106:127 Contributions of a unique β-clamp to substrate recognition illuminates the molecular basis of exolysis in ferulic acid esterases. 27026397 9 10 theme Isothermal 1356:1365 arg1 calorimetry 1377:1387 Isothermal titration calorimetry 1356:1387 Isothermal titration calorimetry 1356:1387 Isothermal titration calorimetry reveals that substrate binding is driven by enthalpic contributions, which overcomes a large entropic penalty. 27026397 5 11 theme Nucleic 905:911 arg1 Acids 913:917 Henrissat (2014) Nucleic Acids 888:917 Henrissat (2014) Nucleic Acids 888:917 The anaerobic fungi (phylum Neocallimastigomycota) are key members of this ecosystem that express a large repertoire of carbohydrate-active enzymes (CAZymes) with little sequence identity with characterized CAZymes [Lombard, Golaconda, Drula, Coutinho and Henrissat (2014) Nucleic Acids Res. 27026397 7 12 dep Anaeromyces 1041:1051 arg1 mucronatus 1053:1062 Anaeromyces mucronatus 1041:1062 Anaeromyces mucronatus(AmCE1/Fae1a) 1041:1075 We have identified a carbohydrate esterase family 1 (CE1) ferulic acid esterase (FAE) belonging to Anaeromyces mucronatus(AmCE1/Fae1a), and determined its X-ray structure in both the presence [1.55 Å (1 Å=0.1 nm)] and absence (1.60 Å) of ferulic acid. 27026397 4 13 theme Ruminant 515:522 arg1 livestock 524:532 Ruminant livestock 515:532 Ruminant livestock 515:532 Ruminant livestock are unique in their ability to degrade lignocellulose through the action of their gut microbiome. 27026397 10 14 theme apparent 1571:1578 arg1 basis 1591:1595 the apparent structural basis 1567:1595 the apparent structural basis for differential FAE activities targeting cross-linking ferulic acid conjugates compared with terminal decorations 1567:1710 A comparative analysis of AmCE1 with related enzymes has uncovered the apparent structural basis for differential FAE activities targeting cross-linking ferulic acid conjugates compared with terminal decorations. 27026397 8 15 theme bacterial 1265:1273 arg1 FAEs 1275:1278 bacterial FAEs 1265:1278 bacterial FAEs 1265:1278 AmCE1 adopts an α/β-hydrolase fold that is structurally conserved with bacterial FAEs, and possesses a unique loop, termed the β-clamp, that encloses the ligand. 27026397 11 16 theme characterized 1750:1762 arg1 FAEs 1764:1767 structurally characterized FAEs 1737:1767 structurally characterized FAEs 1737:1767 Based on comparisons to structurally characterized FAEs, we propose that the β-clamp may define the structural basis of exolytic activities in FAEs. 27026397 5 17 theme carbohydrate-active 752:770 arg1 CAZymes 781:787 CAZymes 781:787 CAZymes 781:787 The anaerobic fungi (phylum Neocallimastigomycota) are key members of this ecosystem that express a large repertoire of carbohydrate-active enzymes (CAZymes) with little sequence identity with characterized CAZymes [Lombard, Golaconda, Drula, Coutinho and Henrissat (2014) Nucleic Acids Res. 27026397 5 17 theme carbohydrate-active 752:770 arg1 enzymes 772:778 carbohydrate-active enzymes 752:778 carbohydrate-active enzymes (CAZymes) with little sequence identity with characterized CAZymes [Lombard, Golaconda, Drula, Coutinho and Henrissat (2014) Nucleic Acids Res 752:921 The anaerobic fungi (phylum Neocallimastigomycota) are key members of this ecosystem that express a large repertoire of carbohydrate-active enzymes (CAZymes) with little sequence identity with characterized CAZymes [Lombard, Golaconda, Drula, Coutinho and Henrissat (2014) Nucleic Acids Res. 27026397 1 18 theme Lignocellulosic 130:144 arg1 resource 179:186 a promising renewable resource 157:186 a promising renewable resource 157:186 Lignocellulosic biomass is a promising renewable resource; however, deconstruction of this material is still the rate-limiting step. 27026397 1 18 theme Lignocellulosic 130:144 arg1 biomass 146:152 Lignocellulosic biomass 130:152 Lignocellulosic biomass 130:152 Lignocellulosic biomass is a promising renewable resource; however, deconstruction of this material is still the rate-limiting step. 27026397 12 19 from endolysis 1927:1935 arg1 CE1 1940:1942 CE1 1940:1942 CE1 1940:1942 This provides a structure-based tool for predicting exolysis and endolysis in CE1. 27026397 7 20 theme acid 1188:1191 arg1 Å 1140:1140 the presence [1.55 Å 1121:1140 the presence [1.55 Å (1 Å=0.1 nm) 1121:1153 We have identified a carbohydrate esterase family 1 (CE1) ferulic acid esterase (FAE) belonging to Anaeromyces mucronatus(AmCE1/Fae1a), and determined its X-ray structure in both the presence [1.55 Å (1 Å=0.1 nm)] and absence (1.60 Å) of ferulic acid. 27026397 7 20 theme acid 1188:1191 arg1 Å 1174:1174 1.60 Å 1169:1174 1.60 Å 1169:1174 We have identified a carbohydrate esterase family 1 (CE1) ferulic acid esterase (FAE) belonging to Anaeromyces mucronatus(AmCE1/Fae1a), and determined its X-ray structure in both the presence [1.55 Å (1 Å=0.1 nm)] and absence (1.60 Å) of ferulic acid. 27026397 7 20 theme acid 1188:1191 arg1 absence 1160:1166 absence 1160:1166 absence 1160:1166 We have identified a carbohydrate esterase family 1 (CE1) ferulic acid esterase (FAE) belonging to Anaeromyces mucronatus(AmCE1/Fae1a), and determined its X-ray structure in both the presence [1.55 Å (1 Å=0.1 nm)] and absence (1.60 Å) of ferulic acid. 27026397 7 20 theme acid 1188:1191 arg1 nm 1151:1152 1 Å=0.1 nm 1143:1152 1 Å=0.1 nm 1143:1152 We have identified a carbohydrate esterase family 1 (CE1) ferulic acid esterase (FAE) belonging to Anaeromyces mucronatus(AmCE1/Fae1a), and determined its X-ray structure in both the presence [1.55 Å (1 Å=0.1 nm)] and absence (1.60 Å) of ferulic acid. 27026397 7 21 theme ferulic 1000:1006 arg1 esterase 1013:1020 a carbohydrate esterase family 1 (CE1) ferulic acid esterase 961:1020 a carbohydrate esterase family 1 (CE1) ferulic acid esterase (FAE) belonging to Anaeromyces mucronatus(AmCE1/Fae1a) 961:1075 We have identified a carbohydrate esterase family 1 (CE1) ferulic acid esterase (FAE) belonging to Anaeromyces mucronatus(AmCE1/Fae1a), and determined its X-ray structure in both the presence [1.55 Å (1 Å=0.1 nm)] and absence (1.60 Å) of ferulic acid. 27026397 7 21 theme ferulic 1000:1006 arg1 FAE 1023:1025 FAE 1023:1025 FAE 1023:1025 We have identified a carbohydrate esterase family 1 (CE1) ferulic acid esterase (FAE) belonging to Anaeromyces mucronatus(AmCE1/Fae1a), and determined its X-ray structure in both the presence [1.55 Å (1 Å=0.1 nm)] and absence (1.60 Å) of ferulic acid. 27026397 9 22 theme large 1476:1480 arg1 penalty 1491:1497 a large entropic penalty 1474:1497 a large entropic penalty 1474:1497 Isothermal titration calorimetry reveals that substrate binding is driven by enthalpic contributions, which overcomes a large entropic penalty. 27026397 12 23 from exolysis 1914:1921 arg1 CE1 1940:1942 CE1 1940:1942 CE1 1940:1942 This provides a structure-based tool for predicting exolysis and endolysis in CE1. 27026397 0 24 theme molecular 75:83 arg1 basis 85:89 the molecular basis 71:89 the molecular basis of exolysis 71:101 Contributions of a unique β-clamp to substrate recognition illuminates the molecular basis of exolysis in ferulic acid esterases. 27026397 5 25 theme phylum 653:658 arg1 fungi 646:650 The anaerobic fungi 632:650 The anaerobic fungi (phylum Neocallimastigomycota) 632:681 The anaerobic fungi (phylum Neocallimastigomycota) are key members of this ecosystem that express a large repertoire of carbohydrate-active enzymes (CAZymes) with little sequence identity with characterized CAZymes [Lombard, Golaconda, Drula, Coutinho and Henrissat (2014) Nucleic Acids Res. 27026397 5 25 theme phylum 653:658 arg1 Neocallimastigomycota 660:680 phylum Neocallimastigomycota 653:680 phylum Neocallimastigomycota 653:680 The anaerobic fungi (phylum Neocallimastigomycota) are key members of this ecosystem that express a large repertoire of carbohydrate-active enzymes (CAZymes) with little sequence identity with characterized CAZymes [Lombard, Golaconda, Drula, Coutinho and Henrissat (2014) Nucleic Acids Res. 27026397 1 26 theme promising 159:167 arg1 resource 179:186 a promising renewable resource 157:186 a promising renewable resource 157:186 Lignocellulosic biomass is a promising renewable resource; however, deconstruction of this material is still the rate-limiting step. 27026397 1 26 theme promising 159:167 arg1 biomass 146:152 Lignocellulosic biomass 130:152 Lignocellulosic biomass 130:152 Lignocellulosic biomass is a promising renewable resource; however, deconstruction of this material is still the rate-limiting step. 27026397 8 27 theme unique 1297:1302 arg1 loop 1304:1307 a unique loop 1295:1307 a unique loop 1295:1307 AmCE1 adopts an α/β-hydrolase fold that is structurally conserved with bacterial FAEs, and possesses a unique loop, termed the β-clamp, that encloses the ligand. 27026397 5 28 theme little 795:800 arg1 identity 811:818 little sequence identity 795:818 little sequence identity with characterized CAZymes [Lombard, Golaconda, Drula, Coutinho and Henrissat (2014) Nucleic Acids Res 795:921 The anaerobic fungi (phylum Neocallimastigomycota) are key members of this ecosystem that express a large repertoire of carbohydrate-active enzymes (CAZymes) with little sequence identity with characterized CAZymes [Lombard, Golaconda, Drula, Coutinho and Henrissat (2014) Nucleic Acids Res. 27026397 7 29 dep Å 1140:1140 arg1 both 1116:1119 both 1116:1119 both 1116:1119 We have identified a carbohydrate esterase family 1 (CE1) ferulic acid esterase (FAE) belonging to Anaeromyces mucronatus(AmCE1/Fae1a), and determined its X-ray structure in both the presence [1.55 Å (1 Å=0.1 nm)] and absence (1.60 Å) of ferulic acid. 27026397 13 30 theme cell 2065:2068 arg1 composition 2075:2085 cell wall composition 2065:2085 cell wall composition 2065:2085 These insights hold promise for rationally identifying enzymes tailored for bioconversion of biomass with variations in cell wall composition. 27026397 12 31 theme structure-based 1878:1892 arg1 tool 1894:1897 a structure-based tool 1876:1897 a structure-based tool for predicting exolysis and endolysis in CE1 1876:1942 This provides a structure-based tool for predicting exolysis and endolysis in CE1. 27026397 7 32 theme esterase 976:983 arg1 esterase 1013:1020 a carbohydrate esterase family 1 (CE1) ferulic acid esterase 961:1020 a carbohydrate esterase family 1 (CE1) ferulic acid esterase (FAE) belonging to Anaeromyces mucronatus(AmCE1/Fae1a) 961:1075 We have identified a carbohydrate esterase family 1 (CE1) ferulic acid esterase (FAE) belonging to Anaeromyces mucronatus(AmCE1/Fae1a), and determined its X-ray structure in both the presence [1.55 Å (1 Å=0.1 nm)] and absence (1.60 Å) of ferulic acid. 27026397 7 32 theme esterase 976:983 arg1 FAE 1023:1025 FAE 1023:1025 FAE 1023:1025 We have identified a carbohydrate esterase family 1 (CE1) ferulic acid esterase (FAE) belonging to Anaeromyces mucronatus(AmCE1/Fae1a), and determined its X-ray structure in both the presence [1.55 Å (1 Å=0.1 nm)] and absence (1.60 Å) of ferulic acid. 27026397 11 33 from activities 1842:1851 arg1 FAEs 1856:1859 FAEs 1856:1859 FAEs 1856:1859 Based on comparisons to structurally characterized FAEs, we propose that the β-clamp may define the structural basis of exolytic activities in FAEs. 27026397 10 34 theme FAE 1614:1616 arg1 activities 1618:1627 differential FAE activities 1601:1627 differential FAE activities targeting cross-linking ferulic acid conjugates compared with terminal decorations 1601:1710 A comparative analysis of AmCE1 with related enzymes has uncovered the apparent structural basis for differential FAE activities targeting cross-linking ferulic acid conjugates compared with terminal decorations. 27026397 11 35 from FAEs 1856:1859 arg1 basis 1824:1828 the structural basis 1809:1828 the structural basis of exolytic activities in FAEs 1809:1859 Based on comparisons to structurally characterized FAEs, we propose that the β-clamp may define the structural basis of exolytic activities in FAEs. 27026397 5 36 theme Henrissat 888:896 arg1 Acids 913:917 Henrissat (2014) Nucleic Acids 888:917 Henrissat (2014) Nucleic Acids 888:917 The anaerobic fungi (phylum Neocallimastigomycota) are key members of this ecosystem that express a large repertoire of carbohydrate-active enzymes (CAZymes) with little sequence identity with characterized CAZymes [Lombard, Golaconda, Drula, Coutinho and Henrissat (2014) Nucleic Acids Res. 27026397 4 37 theme microbiome 620:629 arg1 action 600:605 the action 596:605 the action of their gut microbiome 596:629 Ruminant livestock are unique in their ability to degrade lignocellulose through the action of their gut microbiome. 27026397 10 38 theme ferulic 1653:1659 arg1 conjugates 1666:1675 cross-linking ferulic acid conjugates 1639:1675 cross-linking ferulic acid conjugates 1639:1675 A comparative analysis of AmCE1 with related enzymes has uncovered the apparent structural basis for differential FAE activities targeting cross-linking ferulic acid conjugates compared with terminal decorations. 27026397 0 39 theme β-clamp 26:32 arg1 Contributions 0:12 Contributions 0:12 Contributions of a unique β-clamp to substrate recognition 0:57 Contributions of a unique β-clamp to substrate recognition illuminates the molecular basis of exolysis in ferulic acid esterases. 27026397 5 40 theme characterized 825:837 arg1 Res 919:921 Res 919:921 Res 919:921 The anaerobic fungi (phylum Neocallimastigomycota) are key members of this ecosystem that express a large repertoire of carbohydrate-active enzymes (CAZymes) with little sequence identity with characterized CAZymes [Lombard, Golaconda, Drula, Coutinho and Henrissat (2014) Nucleic Acids Res. 27026397 5 40 theme characterized 825:837 arg1 CAZymes 839:845 characterized CAZymes [Lombard, Golaconda, Drula, Coutinho and Henrissat (2014) Nucleic Acids 825:917 CAZymes 839:845 The anaerobic fungi (phylum Neocallimastigomycota) are key members of this ecosystem that express a large repertoire of carbohydrate-active enzymes (CAZymes) with little sequence identity with characterized CAZymes [Lombard, Golaconda, Drula, Coutinho and Henrissat (2014) Nucleic Acids Res. 27026397 0 41 theme substrate 37:45 arg1 recognition 47:57 substrate recognition 37:57 substrate recognition 37:57 Contributions of a unique β-clamp to substrate recognition illuminates the molecular basis of exolysis in ferulic acid esterases. 27026397 11 42 theme exolytic 1833:1840 arg1 activities 1842:1851 exolytic activities 1833:1851 exolytic activities in FAEs 1833:1859 Based on comparisons to structurally characterized FAEs, we propose that the β-clamp may define the structural basis of exolytic activities in FAEs. 27026397 1 43 theme material 221:228 arg1 deconstruction 198:211 deconstruction 198:211 deconstruction of this material 198:228 Lignocellulosic biomass is a promising renewable resource; however, deconstruction of this material is still the rate-limiting step. 27026397 1 43 theme material 221:228 arg1 step 257:260 the rate-limiting step 239:260 the rate-limiting step 239:260 Lignocellulosic biomass is a promising renewable resource; however, deconstruction of this material is still the rate-limiting step. 27026397 2 44 theme structural 386:395 arg1 polysaccharides 397:411 primary structural polysaccharides 378:411 primary structural polysaccharides 378:411 Major obstacles in the biocatalytic turnover of lignocellulose are ester-linked decorations that prevent access to primary structural polysaccharides. 27026397 2 45 link ester-linked 330:341 arg1 obstacles 269:277 Major obstacles 263:277 Major obstacles in the biocatalytic turnover of lignocellulose 263:324 Major obstacles in the biocatalytic turnover of lignocellulose are ester-linked decorations that prevent access to primary structural polysaccharides. 27026397 2 45 link ester-linked 330:341 arg1 decorations 343:353 ester-linked decorations 330:353 ester-linked decorations that prevent access to primary structural polysaccharides 330:411 Major obstacles in the biocatalytic turnover of lignocellulose are ester-linked decorations that prevent access to primary structural polysaccharides. 27026397 5 46 theme ecosystem 707:715 arg1 fungi 646:650 The anaerobic fungi 632:650 The anaerobic fungi (phylum Neocallimastigomycota) 632:681 The anaerobic fungi (phylum Neocallimastigomycota) are key members of this ecosystem that express a large repertoire of carbohydrate-active enzymes (CAZymes) with little sequence identity with characterized CAZymes [Lombard, Golaconda, Drula, Coutinho and Henrissat (2014) Nucleic Acids Res. 27026397 5 46 theme ecosystem 707:715 arg1 members 691:697 key members 687:697 key members of this ecosystem that express a large repertoire of carbohydrate-active enzymes (CAZymes) with little sequence identity with characterized CAZymes [Lombard, Golaconda, Drula, Coutinho and Henrissat (2014) Nucleic Acids Res 687:921 The anaerobic fungi (phylum Neocallimastigomycota) are key members of this ecosystem that express a large repertoire of carbohydrate-active enzymes (CAZymes) with little sequence identity with characterized CAZymes [Lombard, Golaconda, Drula, Coutinho and Henrissat (2014) Nucleic Acids Res. 27026397 1 47 theme rate-limiting 243:255 arg1 step 257:260 the rate-limiting step 239:260 the rate-limiting step 239:260 Lignocellulosic biomass is a promising renewable resource; however, deconstruction of this material is still the rate-limiting step. 27026397 1 47 theme rate-limiting 243:255 arg1 deconstruction 198:211 deconstruction 198:211 deconstruction of this material 198:228 Lignocellulosic biomass is a promising renewable resource; however, deconstruction of this material is still the rate-limiting step. 27026397 10 48 theme related 1537:1543 arg1 enzymes 1545:1551 related enzymes 1537:1551 related enzymes 1537:1551 A comparative analysis of AmCE1 with related enzymes has uncovered the apparent structural basis for differential FAE activities targeting cross-linking ferulic acid conjugates compared with terminal decorations. 27026397 2 49 theme biocatalytic 286:297 arg1 turnover 299:306 the biocatalytic turnover 282:306 the biocatalytic turnover of lignocellulose 282:324 Major obstacles in the biocatalytic turnover of lignocellulose are ester-linked decorations that prevent access to primary structural polysaccharides. 27026397 9 50 theme titration 1367:1375 arg1 calorimetry 1377:1387 Isothermal titration calorimetry 1356:1387 Isothermal titration calorimetry 1356:1387 Isothermal titration calorimetry reveals that substrate binding is driven by enthalpic contributions, which overcomes a large entropic penalty. 27026397 10 51 theme AmCE1 1526:1530 arg1 analysis 1514:1521 A comparative analysis 1500:1521 A comparative analysis of AmCE1 with related enzymes 1500:1551 A comparative analysis of AmCE1 with related enzymes has uncovered the apparent structural basis for differential FAE activities targeting cross-linking ferulic acid conjugates compared with terminal decorations. 27026397 5 52 theme key 687:689 arg1 fungi 646:650 The anaerobic fungi 632:650 The anaerobic fungi (phylum Neocallimastigomycota) 632:681 The anaerobic fungi (phylum Neocallimastigomycota) are key members of this ecosystem that express a large repertoire of carbohydrate-active enzymes (CAZymes) with little sequence identity with characterized CAZymes [Lombard, Golaconda, Drula, Coutinho and Henrissat (2014) Nucleic Acids Res. 27026397 5 52 theme key 687:689 arg1 members 691:697 key members 687:697 key members of this ecosystem that express a large repertoire of carbohydrate-active enzymes (CAZymes) with little sequence identity with characterized CAZymes [Lombard, Golaconda, Drula, Coutinho and Henrissat (2014) Nucleic Acids Res 687:921 The anaerobic fungi (phylum Neocallimastigomycota) are key members of this ecosystem that express a large repertoire of carbohydrate-active enzymes (CAZymes) with little sequence identity with characterized CAZymes [Lombard, Golaconda, Drula, Coutinho and Henrissat (2014) Nucleic Acids Res. 27026397 1 53 theme renewable 169:177 arg1 resource 179:186 a promising renewable resource 157:186 a promising renewable resource 157:186 Lignocellulosic biomass is a promising renewable resource; however, deconstruction of this material is still the rate-limiting step. 27026397 1 53 theme renewable 169:177 arg1 biomass 146:152 Lignocellulosic biomass 130:152 Lignocellulosic biomass 130:152 Lignocellulosic biomass is a promising renewable resource; however, deconstruction of this material is still the rate-limiting step. 27026397 10 54 with AmCE1 1526:1530 arg1 enzymes 1545:1551 related enzymes 1537:1551 related enzymes 1537:1551 A comparative analysis of AmCE1 with related enzymes has uncovered the apparent structural basis for differential FAE activities targeting cross-linking ferulic acid conjugates compared with terminal decorations. 27026397 4 55 from unique 538:543 arg1 ability 554:560 their ability to degrade lignocellulose through the action of their gut microbiome 548:629 their ability to degrade lignocellulose through the action of their gut microbiome 548:629 Ruminant livestock are unique in their ability to degrade lignocellulose through the action of their gut microbiome. 27026397 9 56 theme substrate 1402:1410 arg1 binding 1412:1418 substrate binding 1402:1418 substrate binding 1402:1418 Isothermal titration calorimetry reveals that substrate binding is driven by enthalpic contributions, which overcomes a large entropic penalty. 27026397 13 57 from variations 2051:2060 arg1 composition 2075:2085 cell wall composition 2065:2085 cell wall composition 2065:2085 These insights hold promise for rationally identifying enzymes tailored for bioconversion of biomass with variations in cell wall composition. 27026397 5 58 theme enzymes 772:778 arg1 CAZymes 781:787 CAZymes 781:787 CAZymes 781:787 The anaerobic fungi (phylum Neocallimastigomycota) are key members of this ecosystem that express a large repertoire of carbohydrate-active enzymes (CAZymes) with little sequence identity with characterized CAZymes [Lombard, Golaconda, Drula, Coutinho and Henrissat (2014) Nucleic Acids Res. 27026397 5 58 theme enzymes 772:778 arg1 repertoire 738:747 a large repertoire 730:747 a large repertoire of carbohydrate-active enzymes (CAZymes) with little sequence identity with characterized CAZymes [Lombard, Golaconda, Drula, Coutinho and Henrissat (2014) Nucleic Acids Res 730:921 The anaerobic fungi (phylum Neocallimastigomycota) are key members of this ecosystem that express a large repertoire of carbohydrate-active enzymes (CAZymes) with little sequence identity with characterized CAZymes [Lombard, Golaconda, Drula, Coutinho and Henrissat (2014) Nucleic Acids Res. 27026397 5 58 theme enzymes 772:778 arg1 enzymes 772:778 carbohydrate-active enzymes 752:778 carbohydrate-active enzymes (CAZymes) with little sequence identity with characterized CAZymes [Lombard, Golaconda, Drula, Coutinho and Henrissat (2014) Nucleic Acids Res 752:921 The anaerobic fungi (phylum Neocallimastigomycota) are key members of this ecosystem that express a large repertoire of carbohydrate-active enzymes (CAZymes) with little sequence identity with characterized CAZymes [Lombard, Golaconda, Drula, Coutinho and Henrissat (2014) Nucleic Acids Res. 27026397 7 59 theme CE1 995:997 arg1 esterase 1013:1020 a carbohydrate esterase family 1 (CE1) ferulic acid esterase 961:1020 a carbohydrate esterase family 1 (CE1) ferulic acid esterase (FAE) belonging to Anaeromyces mucronatus(AmCE1/Fae1a) 961:1075 We have identified a carbohydrate esterase family 1 (CE1) ferulic acid esterase (FAE) belonging to Anaeromyces mucronatus(AmCE1/Fae1a), and determined its X-ray structure in both the presence [1.55 Å (1 Å=0.1 nm)] and absence (1.60 Å) of ferulic acid. 27026397 7 59 theme CE1 995:997 arg1 FAE 1023:1025 FAE 1023:1025 FAE 1023:1025 We have identified a carbohydrate esterase family 1 (CE1) ferulic acid esterase (FAE) belonging to Anaeromyces mucronatus(AmCE1/Fae1a), and determined its X-ray structure in both the presence [1.55 Å (1 Å=0.1 nm)] and absence (1.60 Å) of ferulic acid. 27026397 8 60 contain possesses 1285:1293 arg1 AmCE1 1194:1198 AmCE1 1194:1198 AmCE1 1194:1198 AmCE1 adopts an α/β-hydrolase fold that is structurally conserved with bacterial FAEs, and possesses a unique loop, termed the β-clamp, that encloses the ligand. 27026397 8 60 contain possesses 1285:1293 arg2 loop 1304:1307 a unique loop 1295:1307 a unique loop 1295:1307 AmCE1 adopts an α/β-hydrolase fold that is structurally conserved with bacterial FAEs, and possesses a unique loop, termed the β-clamp, that encloses the ligand. 27026397 8 61 theme α/β-hydrolase 1210:1222 arg1 fold 1224:1227 an α/β-hydrolase fold 1207:1227 an α/β-hydrolase fold that is structurally conserved with bacterial FAEs 1207:1278 AmCE1 adopts an α/β-hydrolase fold that is structurally conserved with bacterial FAEs, and possesses a unique loop, termed the β-clamp, that encloses the ligand. 27026397 5 62 with identity 811:818 arg1 Coutinho 875:882 Coutinho 875:882 Coutinho 875:882 The anaerobic fungi (phylum Neocallimastigomycota) are key members of this ecosystem that express a large repertoire of carbohydrate-active enzymes (CAZymes) with little sequence identity with characterized CAZymes [Lombard, Golaconda, Drula, Coutinho and Henrissat (2014) Nucleic Acids Res. 27026397 5 62 with identity 811:818 arg1 Drula 868:872 Drula 868:872 Drula 868:872 The anaerobic fungi (phylum Neocallimastigomycota) are key members of this ecosystem that express a large repertoire of carbohydrate-active enzymes (CAZymes) with little sequence identity with characterized CAZymes [Lombard, Golaconda, Drula, Coutinho and Henrissat (2014) Nucleic Acids Res. 27026397 5 62 with identity 811:818 arg1 CAZymes 839:845 characterized CAZymes [Lombard, Golaconda, Drula, Coutinho and Henrissat (2014) Nucleic Acids 825:917 CAZymes 839:845 The anaerobic fungi (phylum Neocallimastigomycota) are key members of this ecosystem that express a large repertoire of carbohydrate-active enzymes (CAZymes) with little sequence identity with characterized CAZymes [Lombard, Golaconda, Drula, Coutinho and Henrissat (2014) Nucleic Acids Res. 27026397 5 62 with identity 811:818 arg1 Acids 913:917 Henrissat (2014) Nucleic Acids 888:917 Henrissat (2014) Nucleic Acids 888:917 The anaerobic fungi (phylum Neocallimastigomycota) are key members of this ecosystem that express a large repertoire of carbohydrate-active enzymes (CAZymes) with little sequence identity with characterized CAZymes [Lombard, Golaconda, Drula, Coutinho and Henrissat (2014) Nucleic Acids Res. 27026397 5 62 with identity 811:818 arg1 Res 919:921 Res 919:921 Res 919:921 The anaerobic fungi (phylum Neocallimastigomycota) are key members of this ecosystem that express a large repertoire of carbohydrate-active enzymes (CAZymes) with little sequence identity with characterized CAZymes [Lombard, Golaconda, Drula, Coutinho and Henrissat (2014) Nucleic Acids Res. 27026397 10 63 theme structural 1580:1589 arg1 basis 1591:1595 the apparent structural basis 1567:1595 the apparent structural basis for differential FAE activities targeting cross-linking ferulic acid conjugates compared with terminal decorations 1567:1710 A comparative analysis of AmCE1 with related enzymes has uncovered the apparent structural basis for differential FAE activities targeting cross-linking ferulic acid conjugates compared with terminal decorations. 27026397 5 64 theme large 732:736 arg1 CAZymes 781:787 CAZymes 781:787 CAZymes 781:787 The anaerobic fungi (phylum Neocallimastigomycota) are key members of this ecosystem that express a large repertoire of carbohydrate-active enzymes (CAZymes) with little sequence identity with characterized CAZymes [Lombard, Golaconda, Drula, Coutinho and Henrissat (2014) Nucleic Acids Res. 27026397 5 64 theme large 732:736 arg1 repertoire 738:747 a large repertoire 730:747 a large repertoire of carbohydrate-active enzymes (CAZymes) with little sequence identity with characterized CAZymes [Lombard, Golaconda, Drula, Coutinho and Henrissat (2014) Nucleic Acids Res 730:921 The anaerobic fungi (phylum Neocallimastigomycota) are key members of this ecosystem that express a large repertoire of carbohydrate-active enzymes (CAZymes) with little sequence identity with characterized CAZymes [Lombard, Golaconda, Drula, Coutinho and Henrissat (2014) Nucleic Acids Res. 27026397 5 64 theme large 732:736 arg1 enzymes 772:778 carbohydrate-active enzymes 752:778 carbohydrate-active enzymes (CAZymes) with little sequence identity with characterized CAZymes [Lombard, Golaconda, Drula, Coutinho and Henrissat (2014) Nucleic Acids Res 752:921 The anaerobic fungi (phylum Neocallimastigomycota) are key members of this ecosystem that express a large repertoire of carbohydrate-active enzymes (CAZymes) with little sequence identity with characterized CAZymes [Lombard, Golaconda, Drula, Coutinho and Henrissat (2014) Nucleic Acids Res. 27026397 11 65 theme structural 1813:1822 arg1 basis 1824:1828 the structural basis 1809:1828 the structural basis of exolytic activities in FAEs 1809:1859 Based on comparisons to structurally characterized FAEs, we propose that the β-clamp may define the structural basis of exolytic activities in FAEs. 27026397 2 66 theme Major 263:267 arg1 obstacles 269:277 Major obstacles 263:277 Major obstacles in the biocatalytic turnover of lignocellulose 263:324 Major obstacles in the biocatalytic turnover of lignocellulose are ester-linked decorations that prevent access to primary structural polysaccharides. 27026397 2 66 theme Major 263:267 arg1 decorations 343:353 ester-linked decorations 330:353 ester-linked decorations that prevent access to primary structural polysaccharides 330:411 Major obstacles in the biocatalytic turnover of lignocellulose are ester-linked decorations that prevent access to primary structural polysaccharides. 27026397 2 67 from obstacles 269:277 arg1 turnover 299:306 the biocatalytic turnover 282:306 the biocatalytic turnover of lignocellulose 282:324 Major obstacles in the biocatalytic turnover of lignocellulose are ester-linked decorations that prevent access to primary structural polysaccharides. 27026397 7 68 theme ferulic 1180:1186 arg1 acid 1188:1191 ferulic acid 1180:1191 ferulic acid 1180:1191 We have identified a carbohydrate esterase family 1 (CE1) ferulic acid esterase (FAE) belonging to Anaeromyces mucronatus(AmCE1/Fae1a), and determined its X-ray structure in both the presence [1.55 Å (1 Å=0.1 nm)] and absence (1.60 Å) of ferulic acid. 27026397 7 69 theme acid 1008:1011 arg1 esterase 1013:1020 a carbohydrate esterase family 1 (CE1) ferulic acid esterase 961:1020 a carbohydrate esterase family 1 (CE1) ferulic acid esterase (FAE) belonging to Anaeromyces mucronatus(AmCE1/Fae1a) 961:1075 We have identified a carbohydrate esterase family 1 (CE1) ferulic acid esterase (FAE) belonging to Anaeromyces mucronatus(AmCE1/Fae1a), and determined its X-ray structure in both the presence [1.55 Å (1 Å=0.1 nm)] and absence (1.60 Å) of ferulic acid. 27026397 7 69 theme acid 1008:1011 arg1 FAE 1023:1025 FAE 1023:1025 FAE 1023:1025 We have identified a carbohydrate esterase family 1 (CE1) ferulic acid esterase (FAE) belonging to Anaeromyces mucronatus(AmCE1/Fae1a), and determined its X-ray structure in both the presence [1.55 Å (1 Å=0.1 nm)] and absence (1.60 Å) of ferulic acid. 27026397 9 70 theme entropic 1482:1489 arg1 penalty 1491:1497 a large entropic penalty 1474:1497 a large entropic penalty 1474:1497 Isothermal titration calorimetry reveals that substrate binding is driven by enthalpic contributions, which overcomes a large entropic penalty. 27026397 0 71 theme exolysis 94:101 arg1 basis 85:89 the molecular basis 71:89 the molecular basis of exolysis 71:101 Contributions of a unique β-clamp to substrate recognition illuminates the molecular basis of exolysis in ferulic acid esterases. 27026397 2 72 theme ester-linked 330:341 arg1 obstacles 269:277 Major obstacles 263:277 Major obstacles in the biocatalytic turnover of lignocellulose 263:324 Major obstacles in the biocatalytic turnover of lignocellulose are ester-linked decorations that prevent access to primary structural polysaccharides. 27026397 2 72 theme ester-linked 330:341 arg1 decorations 343:353 ester-linked decorations 330:353 ester-linked decorations that prevent access to primary structural polysaccharides 330:411 Major obstacles in the biocatalytic turnover of lignocellulose are ester-linked decorations that prevent access to primary structural polysaccharides. 27026397 0 73 theme ferulic 106:112 arg1 esterases 119:127 ferulic acid esterases 106:127 ferulic acid esterases 106:127 Contributions of a unique β-clamp to substrate recognition illuminates the molecular basis of exolysis in ferulic acid esterases. 27026397 3 74 theme bioconversion 489:501 arg1 efficiency 503:512 bioconversion efficiency 489:512 bioconversion efficiency 489:512 Enzymes targeting these esters represent promising biotools for increasing bioconversion efficiency. 27026397 13 75 theme wall 2070:2073 arg1 composition 2075:2085 cell wall composition 2065:2085 cell wall composition 2065:2085 These insights hold promise for rationally identifying enzymes tailored for bioconversion of biomass with variations in cell wall composition. 27026397 7 76 theme family 985:990 arg1 esterase 1013:1020 a carbohydrate esterase family 1 (CE1) ferulic acid esterase 961:1020 a carbohydrate esterase family 1 (CE1) ferulic acid esterase (FAE) belonging to Anaeromyces mucronatus(AmCE1/Fae1a) 961:1075 We have identified a carbohydrate esterase family 1 (CE1) ferulic acid esterase (FAE) belonging to Anaeromyces mucronatus(AmCE1/Fae1a), and determined its X-ray structure in both the presence [1.55 Å (1 Å=0.1 nm)] and absence (1.60 Å) of ferulic acid. 27026397 7 76 theme family 985:990 arg1 FAE 1023:1025 FAE 1023:1025 FAE 1023:1025 We have identified a carbohydrate esterase family 1 (CE1) ferulic acid esterase (FAE) belonging to Anaeromyces mucronatus(AmCE1/Fae1a), and determined its X-ray structure in both the presence [1.55 Å (1 Å=0.1 nm)] and absence (1.60 Å) of ferulic acid. 27026397 4 77 theme gut 616:618 arg1 microbiome 620:629 their gut microbiome 610:629 their gut microbiome 610:629 Ruminant livestock are unique in their ability to degrade lignocellulose through the action of their gut microbiome. 27026397 10 78 theme differential 1601:1612 arg1 activities 1618:1627 differential FAE activities 1601:1627 differential FAE activities targeting cross-linking ferulic acid conjugates compared with terminal decorations 1601:1710 A comparative analysis of AmCE1 with related enzymes has uncovered the apparent structural basis for differential FAE activities targeting cross-linking ferulic acid conjugates compared with terminal decorations. 27026397 0 79 theme unique 19:24 arg1 β-clamp 26:32 a unique β-clamp 17:32 a unique β-clamp 17:32 Contributions of a unique β-clamp to substrate recognition illuminates the molecular basis of exolysis in ferulic acid esterases. 27026397 7 80 theme carbohydrate 963:974 arg1 esterase 1013:1020 a carbohydrate esterase family 1 (CE1) ferulic acid esterase 961:1020 a carbohydrate esterase family 1 (CE1) ferulic acid esterase (FAE) belonging to Anaeromyces mucronatus(AmCE1/Fae1a) 961:1075 We have identified a carbohydrate esterase family 1 (CE1) ferulic acid esterase (FAE) belonging to Anaeromyces mucronatus(AmCE1/Fae1a), and determined its X-ray structure in both the presence [1.55 Å (1 Å=0.1 nm)] and absence (1.60 Å) of ferulic acid. 27026397 7 80 theme carbohydrate 963:974 arg1 FAE 1023:1025 FAE 1023:1025 FAE 1023:1025 We have identified a carbohydrate esterase family 1 (CE1) ferulic acid esterase (FAE) belonging to Anaeromyces mucronatus(AmCE1/Fae1a), and determined its X-ray structure in both the presence [1.55 Å (1 Å=0.1 nm)] and absence (1.60 Å) of ferulic acid. 27026397 7 81 from structure 1103:1111 arg1 Å 1140:1140 the presence [1.55 Å 1121:1140 the presence [1.55 Å (1 Å=0.1 nm) 1121:1153 We have identified a carbohydrate esterase family 1 (CE1) ferulic acid esterase (FAE) belonging to Anaeromyces mucronatus(AmCE1/Fae1a), and determined its X-ray structure in both the presence [1.55 Å (1 Å=0.1 nm)] and absence (1.60 Å) of ferulic acid. 27026397 7 81 from structure 1103:1111 arg1 Å 1174:1174 1.60 Å 1169:1174 1.60 Å 1169:1174 We have identified a carbohydrate esterase family 1 (CE1) ferulic acid esterase (FAE) belonging to Anaeromyces mucronatus(AmCE1/Fae1a), and determined its X-ray structure in both the presence [1.55 Å (1 Å=0.1 nm)] and absence (1.60 Å) of ferulic acid. 27026397 7 81 from structure 1103:1111 arg1 absence 1160:1166 absence 1160:1166 absence 1160:1166 We have identified a carbohydrate esterase family 1 (CE1) ferulic acid esterase (FAE) belonging to Anaeromyces mucronatus(AmCE1/Fae1a), and determined its X-ray structure in both the presence [1.55 Å (1 Å=0.1 nm)] and absence (1.60 Å) of ferulic acid. 27026397 7 81 from structure 1103:1111 arg1 nm 1151:1152 1 Å=0.1 nm 1143:1152 1 Å=0.1 nm 1143:1152 We have identified a carbohydrate esterase family 1 (CE1) ferulic acid esterase (FAE) belonging to Anaeromyces mucronatus(AmCE1/Fae1a), and determined its X-ray structure in both the presence [1.55 Å (1 Å=0.1 nm)] and absence (1.60 Å) of ferulic acid. 27026397 10 82 theme acid 1661:1664 arg1 conjugates 1666:1675 cross-linking ferulic acid conjugates 1639:1675 cross-linking ferulic acid conjugates 1639:1675 A comparative analysis of AmCE1 with related enzymes has uncovered the apparent structural basis for differential FAE activities targeting cross-linking ferulic acid conjugates compared with terminal decorations. 27026397 5 83 with enzymes 772:778 arg1 identity 811:818 little sequence identity 795:818 little sequence identity with characterized CAZymes [Lombard, Golaconda, Drula, Coutinho and Henrissat (2014) Nucleic Acids Res 795:921 The anaerobic fungi (phylum Neocallimastigomycota) are key members of this ecosystem that express a large repertoire of carbohydrate-active enzymes (CAZymes) with little sequence identity with characterized CAZymes [Lombard, Golaconda, Drula, Coutinho and Henrissat (2014) Nucleic Acids Res. 27026397 3 84 theme promising 455:463 arg1 biotools 465:472 promising biotools 455:472 promising biotools 455:472 Enzymes targeting these esters represent promising biotools for increasing bioconversion efficiency. 27026397 10 85 theme cross-linking 1639:1651 arg1 conjugates 1666:1675 cross-linking ferulic acid conjugates 1639:1675 cross-linking ferulic acid conjugates 1639:1675 A comparative analysis of AmCE1 with related enzymes has uncovered the apparent structural basis for differential FAE activities targeting cross-linking ferulic acid conjugates compared with terminal decorations. 27026397 13 86 theme biomass 2038:2044 arg1 bioconversion 2021:2033 bioconversion 2021:2033 bioconversion of biomass with variations in cell wall composition 2021:2085 These insights hold promise for rationally identifying enzymes tailored for bioconversion of biomass with variations in cell wall composition. 27026397 10 87 theme terminal 1691:1698 arg1 decorations 1700:1710 terminal decorations 1691:1710 terminal decorations 1691:1710 A comparative analysis of AmCE1 with related enzymes has uncovered the apparent structural basis for differential FAE activities targeting cross-linking ferulic acid conjugates compared with terminal decorations. 27026397 5 88 theme sequence 802:809 arg1 identity 811:818 little sequence identity 795:818 little sequence identity with characterized CAZymes [Lombard, Golaconda, Drula, Coutinho and Henrissat (2014) Nucleic Acids Res 795:921 The anaerobic fungi (phylum Neocallimastigomycota) are key members of this ecosystem that express a large repertoire of carbohydrate-active enzymes (CAZymes) with little sequence identity with characterized CAZymes [Lombard, Golaconda, Drula, Coutinho and Henrissat (2014) Nucleic Acids Res. 27026397 11 89 theme activities 1842:1851 arg1 basis 1824:1828 the structural basis 1809:1828 the structural basis of exolytic activities in FAEs 1809:1859 Based on comparisons to structurally characterized FAEs, we propose that the β-clamp may define the structural basis of exolytic activities in FAEs. 27026397 9 90 theme enthalpic 1433:1441 arg1 contributions 1443:1455 enthalpic contributions 1433:1455 enthalpic contributions 1433:1455 Isothermal titration calorimetry reveals that substrate binding is driven by enthalpic contributions, which overcomes a large entropic penalty. 27026397 10 91 theme comparative 1502:1512 arg1 analysis 1514:1521 A comparative analysis 1500:1521 A comparative analysis of AmCE1 with related enzymes 1500:1551 A comparative analysis of AmCE1 with related enzymes has uncovered the apparent structural basis for differential FAE activities targeting cross-linking ferulic acid conjugates compared with terminal decorations. 27026397 2 92 theme primary 378:384 arg1 polysaccharides 397:411 primary structural polysaccharides 378:411 primary structural polysaccharides 378:411 Major obstacles in the biocatalytic turnover of lignocellulose are ester-linked decorations that prevent access to primary structural polysaccharides. 26559645 6 0 theme mono- 579:583 arg1 number 569:574 a number 567:574 a number of mono-, di- and polysaccharides 567:608 The isolate grew anaerobically using a number of mono-, di- and polysaccharides as electron donors and nitrate or elemental sulfur as electron acceptors or by fermentation. 26559645 6 0 theme mono- 579:583 arg1 donors 622:627 electron donors 613:627 electron donors 613:627 The isolate grew anaerobically using a number of mono-, di- and polysaccharides as electron donors and nitrate or elemental sulfur as electron acceptors or by fermentation. 26559645 6 1 theme electron 613:620 arg1 number 569:574 a number 567:574 a number of mono-, di- and polysaccharides 567:608 The isolate grew anaerobically using a number of mono-, di- and polysaccharides as electron donors and nitrate or elemental sulfur as electron acceptors or by fermentation. 26559645 6 1 theme electron 613:620 arg1 donors 622:627 electron donors 613:627 electron donors 613:627 The isolate grew anaerobically using a number of mono-, di- and polysaccharides as electron donors and nitrate or elemental sulfur as electron acceptors or by fermentation. 26559645 10 2 theme name 1137:1140 arg1 nov. 1167:1170 the name Thermostilla marina gen. nov. 1133:1170 the name Thermostilla marina gen. nov. 1133:1170 Based on phylogenetic position and phenotypic features, the new isolate is considered to represent a novel species belonging to a new genus in the order Planctomycetales, for which the name Thermostilla marina gen. nov., sp. 26559645 10 3 theme gen. 1162:1165 arg1 nov. 1167:1170 the name Thermostilla marina gen. nov. 1133:1170 the name Thermostilla marina gen. nov. 1133:1170 Based on phylogenetic position and phenotypic features, the new isolate is considered to represent a novel species belonging to a new genus in the order Planctomycetales, for which the name Thermostilla marina gen. nov., sp. 26559645 8 4 from oxygen 868:873 arg1 phase 886:890 the gas phase 878:890 the gas phase 878:890 Strain SVX8T did not grow at atmospheric concentration of oxygen but grew microaerobically (up to 2 % oxygen in the gas phase). 26559645 10 5 theme new 1082:1084 arg1 genus 1086:1090 a new genus 1080:1090 a new genus 1080:1090 Based on phylogenetic position and phenotypic features, the new isolate is considered to represent a novel species belonging to a new genus in the order Planctomycetales, for which the name Thermostilla marina gen. nov., sp. 26559645 4 6 theme pH 355:356 arg1 range 358:362 The pH range 351:362 The pH range for growth 351:373 The pH range for growth was 5.0-9.0, with an optimum at pH 7.0-8.0. 26559645 4 6 theme pH 355:356 arg1 5.0-9.0 379:385 5.0-9.0 379:385 5.0-9.0 379:385 The pH range for growth was 5.0-9.0, with an optimum at pH 7.0-8.0. 26559645 5 7 with % 486:486 arg1 optimum 502:508 an optimum 499:508 an optimum 499:508 Growth was observed at NaCl concentrations ranging from 0.8 to 4.5 % (w/v) with an optimum at 2.5-3.5 % (w/v). 26559645 9 8 theme 58.5 mol 941:948 arg1 content 902:908 The G+C content 894:908 The G+C content of the DNA of strain SVX8T 894:935 The G+C content of the DNA of strain SVX8T was 58.5 mol%. 26559645 9 8 theme 58.5 mol 941:948 arg1 % 949:949 58.5 mol% 941:949 58.5 mol% 941:949 The G+C content of the DNA of strain SVX8T was 58.5 mol%. 26559645 12 9 theme type 1199:1202 arg1 SVX8T 1237:1241 SVX8T 1237:1241 SVX8T ( = JCM 19992T = VKM B-2881T) 1237:1271 The type strain of Thermostilla marina is SVX8T ( = JCM 19992T = VKM B-2881T). 26559645 12 9 theme type 1199:1202 arg1 strain 1204:1209 The type strain 1195:1209 The type strain of Thermostilla marina 1195:1232 The type strain of Thermostilla marina is SVX8T ( = JCM 19992T = VKM B-2881T). 26559645 9 10 theme DNA 917:919 arg1 content 902:908 The G+C content 894:908 The G+C content of the DNA of strain SVX8T 894:935 The G+C content of the DNA of strain SVX8T was 58.5 mol%. 26559645 9 10 theme DNA 917:919 arg1 % 949:949 58.5 mol% 941:949 58.5 mol% 941:949 The G+C content of the DNA of strain SVX8T was 58.5 mol%. 26559645 8 11 theme Strain 766:771 arg1 SVX8T 773:777 Strain SVX8T 766:777 Strain SVX8T 766:777 Strain SVX8T did not grow at atmospheric concentration of oxygen but grew microaerobically (up to 2 % oxygen in the gas phase). 26559645 12 12 theme marina 1227:1232 arg1 SVX8T 1237:1241 SVX8T 1237:1241 SVX8T ( = JCM 19992T = VKM B-2881T) 1237:1271 The type strain of Thermostilla marina is SVX8T ( = JCM 19992T = VKM B-2881T). 26559645 12 12 theme marina 1227:1232 arg1 strain 1204:1209 The type strain 1195:1209 The type strain of Thermostilla marina 1195:1232 The type strain of Thermostilla marina is SVX8T ( = JCM 19992T = VKM B-2881T). 26559645 3 13 from 55 °C 344:348 arg1 optimum 333:339 an optimum 330:339 an optimum at 55 °C 330:348 The temperature range for growth was 30-68 °C, with an optimum at 55 °C. 26559645 13 14 theme Strain 1274:1279 arg1 SVX8T 1281:1285 Strain SVX8T 1274:1285 Strain SVX8T 1274:1285 Strain SVX8T is the first thermophilic planctomycete isolated from a marine environment. 26559645 13 14 theme Strain 1274:1279 arg1 planctomycete 1313:1325 planctomycete 1313:1325 planctomycete 1313:1325 Strain SVX8T is the first thermophilic planctomycete isolated from a marine environment. 26559645 12 15 theme Thermostilla 1214:1225 arg1 marina 1227:1232 Thermostilla marina 1214:1232 Thermostilla marina 1214:1232 The type strain of Thermostilla marina is SVX8T ( = JCM 19992T = VKM B-2881T). 26559645 5 16 theme NaCl 442:445 arg1 concentrations 447:460 NaCl concentrations 442:460 NaCl concentrations ranging from 0.8 to 4.5 % (w/v) with an optimum at 2.5-3.5 % (w/v) 442:527 Growth was observed at NaCl concentrations ranging from 0.8 to 4.5 % (w/v) with an optimum at 2.5-3.5 % (w/v). 26559645 10 17 theme marina 1155:1160 arg1 nov. 1167:1170 the name Thermostilla marina gen. nov. 1133:1170 the name Thermostilla marina gen. nov. 1133:1170 Based on phylogenetic position and phenotypic features, the new isolate is considered to represent a novel species belonging to a new genus in the order Planctomycetales, for which the name Thermostilla marina gen. nov., sp. 26559645 9 18 theme strain 924:929 arg1 SVX8T 931:935 strain SVX8T 924:935 strain SVX8T 924:935 The G+C content of the DNA of strain SVX8T was 58.5 mol%. 26559645 0 19 theme marina 13:18 arg1 nov. 25:28 Thermostilla marina gen. nov. 0:28 Thermostilla marina gen. nov. 0:28 Thermostilla marina gen. nov., sp. 26559645 6 20 theme di- 586:588 arg1 number 569:574 a number 567:574 a number of mono-, di- and polysaccharides 567:608 The isolate grew anaerobically using a number of mono-, di- and polysaccharides as electron donors and nitrate or elemental sulfur as electron acceptors or by fermentation. 26559645 6 20 theme di- 586:588 arg1 donors 622:627 electron donors 613:627 electron donors 613:627 The isolate grew anaerobically using a number of mono-, di- and polysaccharides as electron donors and nitrate or elemental sulfur as electron acceptors or by fermentation. 26559645 13 21 theme marine 1343:1348 arg1 environment 1350:1360 a marine environment 1341:1360 a marine environment 1341:1360 Strain SVX8T is the first thermophilic planctomycete isolated from a marine environment. 26559645 0 22 theme Thermostilla 0:11 arg1 nov. 25:28 Thermostilla marina gen. nov. 0:28 Thermostilla marina gen. nov. 0:28 Thermostilla marina gen. nov., sp. 26559645 10 23 dep sp 1173:1174 arg1 nov. 1167:1170 the name Thermostilla marina gen. nov. 1133:1170 the name Thermostilla marina gen. nov. 1133:1170 Based on phylogenetic position and phenotypic features, the new isolate is considered to represent a novel species belonging to a new genus in the order Planctomycetales, for which the name Thermostilla marina gen. nov., sp. 26559645 8 24 theme gas 882:884 arg1 phase 886:890 the gas phase 878:890 the gas phase 878:890 Strain SVX8T did not grow at atmospheric concentration of oxygen but grew microaerobically (up to 2 % oxygen in the gas phase). 26559645 8 25 dep % 866:866 arg1 2  864:865 2  864:865 2  864:865 Strain SVX8T did not grow at atmospheric concentration of oxygen but grew microaerobically (up to 2 % oxygen in the gas phase). 26559645 10 26 theme phylogenetic 961:972 arg1 position 974:981 phylogenetic position 961:981 phylogenetic position 961:981 Based on phylogenetic position and phenotypic features, the new isolate is considered to represent a novel species belonging to a new genus in the order Planctomycetales, for which the name Thermostilla marina gen. nov., sp. 26559645 4 27 from pH 7.0-8.0 407:416 arg1 optimum 396:402 an optimum 393:402 an optimum at pH 7.0-8.0 393:416 The pH range for growth was 5.0-9.0, with an optimum at pH 7.0-8.0. 26559645 6 28 theme electron 664:671 arg1 acceptors 673:681 electron acceptors 664:681 electron acceptors 664:681 The isolate grew anaerobically using a number of mono-, di- and polysaccharides as electron donors and nitrate or elemental sulfur as electron acceptors or by fermentation. 26559645 5 29 dep 4.5  482:485 arg1 to 479:480 to 479:480 to 479:480 Growth was observed at NaCl concentrations ranging from 0.8 to 4.5 % (w/v) with an optimum at 2.5-3.5 % (w/v). 26559645 0 30 theme gen. 20:23 arg1 nov. 25:28 Thermostilla marina gen. nov. 0:28 Thermostilla marina gen. nov. 0:28 Thermostilla marina gen. nov., sp. 26559645 8 31 theme oxygen 824:829 arg1 concentration 807:819 atmospheric concentration 795:819 atmospheric concentration of oxygen 795:829 Strain SVX8T did not grow at atmospheric concentration of oxygen but grew microaerobically (up to 2 % oxygen in the gas phase). 26559645 10 32 from genus 1086:1090 arg1 Planctomycetales 1105:1120 the order Planctomycetales 1095:1120 the order Planctomycetales 1095:1120 Based on phylogenetic position and phenotypic features, the new isolate is considered to represent a novel species belonging to a new genus in the order Planctomycetales, for which the name Thermostilla marina gen. nov., sp. 26559645 1 33 theme hydrothermal 129:140 arg1 vent 142:145 a shallow submarine hydrothermal vent 109:145 a shallow submarine hydrothermal vent 109:145 nov., a thermophilic, facultatively anaerobic planctomycete isolated from a shallow submarine hydrothermal vent. 26559645 6 34 theme polysaccharides 594:608 arg1 number 569:574 a number 567:574 a number of mono-, di- and polysaccharides 567:608 The isolate grew anaerobically using a number of mono-, di- and polysaccharides as electron donors and nitrate or elemental sulfur as electron acceptors or by fermentation. 26559645 6 34 theme polysaccharides 594:608 arg1 donors 622:627 electron donors 613:627 electron donors 613:627 The isolate grew anaerobically using a number of mono-, di- and polysaccharides as electron donors and nitrate or elemental sulfur as electron acceptors or by fermentation. 26559645 2 35 theme shallow 218:224 arg1 Italy 271:275 Italy 271:275 Italy 271:275 A novel thermophilic planctomycete (strain SVX8T) was isolated from a shallow submarine hydrothermal vent, Vulcano Island, Italy. 26559645 2 35 theme shallow 218:224 arg1 Island 263:268 a shallow submarine hydrothermal vent, Vulcano Island 216:268 Island 263:268 A novel thermophilic planctomycete (strain SVX8T) was isolated from a shallow submarine hydrothermal vent, Vulcano Island, Italy. 26559645 9 36 theme SVX8T 931:935 arg1 DNA 917:919 the DNA 913:919 the DNA of strain SVX8T 913:935 The G+C content of the DNA of strain SVX8T was 58.5 mol%. 26559645 13 37 attach isolated 1327:1334 arg2 planctomycete 1313:1325 planctomycete 1313:1325 planctomycete 1313:1325 Strain SVX8T is the first thermophilic planctomycete isolated from a marine environment. 26559645 13 37 attach isolated 1327:1334 arg1 environment 1350:1360 a marine environment 1341:1360 a marine environment 1341:1360 Strain SVX8T is the first thermophilic planctomycete isolated from a marine environment. 26559645 13 37 attach isolated 1327:1334 arg2 SVX8T 1281:1285 Strain SVX8T 1274:1285 Strain SVX8T 1274:1285 Strain SVX8T is the first thermophilic planctomycete isolated from a marine environment. 26559645 3 38 theme temperature 282:292 arg1 range 294:298 The temperature range 278:298 The temperature range for growth 278:309 The temperature range for growth was 30-68 °C, with an optimum at 55 °C. 26559645 0 39 dep sp 31:32 arg1 nov. 25:28 Thermostilla marina gen. nov. 0:28 Thermostilla marina gen. nov. 0:28 Thermostilla marina gen. nov., sp. 26559645 8 40 theme atmospheric 795:805 arg1 concentration 807:819 atmospheric concentration 795:819 atmospheric concentration of oxygen 795:829 Strain SVX8T did not grow at atmospheric concentration of oxygen but grew microaerobically (up to 2 % oxygen in the gas phase). 26559645 1 41 dep thermophilic 43:54 arg1 anaerobic 71:79 anaerobic 71:79 anaerobic 71:79 nov., a thermophilic, facultatively anaerobic planctomycete isolated from a shallow submarine hydrothermal vent. 26559645 10 42 theme phenotypic 987:996 arg1 features 998:1005 phenotypic features 987:1005 phenotypic features 987:1005 Based on phylogenetic position and phenotypic features, the new isolate is considered to represent a novel species belonging to a new genus in the order Planctomycetales, for which the name Thermostilla marina gen. nov., sp. 26559645 8 43 dep oxygen 868:873 arg1 % 866:866 % 866:866 % 866:866 Strain SVX8T did not grow at atmospheric concentration of oxygen but grew microaerobically (up to 2 % oxygen in the gas phase). 26559645 6 44 theme elemental 644:652 arg1 sulfur 654:659 elemental sulfur 644:659 elemental sulfur 644:659 The isolate grew anaerobically using a number of mono-, di- and polysaccharides as electron donors and nitrate or elemental sulfur as electron acceptors or by fermentation. 26559645 8 45 dep 2  864:865 arg1 to 861:862 to 861:862 to 861:862 Strain SVX8T did not grow at atmospheric concentration of oxygen but grew microaerobically (up to 2 % oxygen in the gas phase). 26559645 5 46 located observed 430:437 arg1 concentrations 447:460 NaCl concentrations 442:460 NaCl concentrations ranging from 0.8 to 4.5 % (w/v) with an optimum at 2.5-3.5 % (w/v) 442:527 Growth was observed at NaCl concentrations ranging from 0.8 to 4.5 % (w/v) with an optimum at 2.5-3.5 % (w/v). 26559645 5 46 located observed 430:437 arg2 Growth 419:424 Growth 419:424 Growth 419:424 Growth was observed at NaCl concentrations ranging from 0.8 to 4.5 % (w/v) with an optimum at 2.5-3.5 % (w/v). 26559645 10 47 theme Thermostilla 1142:1153 arg1 nov. 1167:1170 the name Thermostilla marina gen. nov. 1133:1170 the name Thermostilla marina gen. nov. 1133:1170 Based on phylogenetic position and phenotypic features, the new isolate is considered to represent a novel species belonging to a new genus in the order Planctomycetales, for which the name Thermostilla marina gen. nov., sp. 26559645 1 48 theme shallow 111:117 arg1 vent 142:145 a shallow submarine hydrothermal vent 109:145 a shallow submarine hydrothermal vent 109:145 nov., a thermophilic, facultatively anaerobic planctomycete isolated from a shallow submarine hydrothermal vent. 26559645 2 49 theme vent 249:252 arg1 Italy 271:275 Italy 271:275 Italy 271:275 A novel thermophilic planctomycete (strain SVX8T) was isolated from a shallow submarine hydrothermal vent, Vulcano Island, Italy. 26559645 2 49 theme vent 249:252 arg1 Island 263:268 a shallow submarine hydrothermal vent, Vulcano Island 216:268 Island 263:268 A novel thermophilic planctomycete (strain SVX8T) was isolated from a shallow submarine hydrothermal vent, Vulcano Island, Italy. 26559645 1 50 theme submarine 119:127 arg1 vent 142:145 a shallow submarine hydrothermal vent 109:145 a shallow submarine hydrothermal vent 109:145 nov., a thermophilic, facultatively anaerobic planctomycete isolated from a shallow submarine hydrothermal vent. 26559645 8 51 dep grew 835:838 arg1 oxygen 868:873 up to 2 % oxygen 858:873 up to 2 % oxygen in the gas phase 858:890 Strain SVX8T did not grow at atmospheric concentration of oxygen but grew microaerobically (up to 2 % oxygen in the gas phase). 26559645 10 52 theme order 1099:1103 arg1 Planctomycetales 1105:1120 the order Planctomycetales 1095:1120 the order Planctomycetales 1095:1120 Based on phylogenetic position and phenotypic features, the new isolate is considered to represent a novel species belonging to a new genus in the order Planctomycetales, for which the name Thermostilla marina gen. nov., sp. 26559645 2 53 theme strain 184:189 arg1 planctomycete 169:181 planctomycete 169:181 planctomycete 169:181 A novel thermophilic planctomycete (strain SVX8T) was isolated from a shallow submarine hydrothermal vent, Vulcano Island, Italy. 26559645 2 53 theme strain 184:189 arg1 SVX8T 191:195 strain SVX8T 184:195 strain SVX8T 184:195 A novel thermophilic planctomycete (strain SVX8T) was isolated from a shallow submarine hydrothermal vent, Vulcano Island, Italy. 26559645 2 54 theme hydrothermal 236:247 arg1 Italy 271:275 Italy 271:275 Italy 271:275 A novel thermophilic planctomycete (strain SVX8T) was isolated from a shallow submarine hydrothermal vent, Vulcano Island, Italy. 26559645 2 54 theme hydrothermal 236:247 arg1 Island 263:268 a shallow submarine hydrothermal vent, Vulcano Island 216:268 Island 263:268 A novel thermophilic planctomycete (strain SVX8T) was isolated from a shallow submarine hydrothermal vent, Vulcano Island, Italy. 26559645 2 55 dep Island 263:268 arg1 Vulcano 255:261 a shallow submarine hydrothermal vent, Vulcano Island 216:268 Vulcano 255:261 A novel thermophilic planctomycete (strain SVX8T) was isolated from a shallow submarine hydrothermal vent, Vulcano Island, Italy. 26559645 10 56 theme novel 1053:1057 arg1 species 1059:1065 a novel species 1051:1065 a novel species belonging to a new genus in the order Planctomycetales, for which the name Thermostilla marina gen. nov., sp 1051:1174 Based on phylogenetic position and phenotypic features, the new isolate is considered to represent a novel species belonging to a new genus in the order Planctomycetales, for which the name Thermostilla marina gen. nov., sp. 26559645 10 57 theme new 1012:1014 arg1 isolate 1016:1022 the new isolate 1008:1022 the new isolate 1008:1022 Based on phylogenetic position and phenotypic features, the new isolate is considered to represent a novel species belonging to a new genus in the order Planctomycetales, for which the name Thermostilla marina gen. nov., sp. 26559645 2 58 attach isolated 202:209 arg2 SVX8T 191:195 strain SVX8T 184:195 strain SVX8T 184:195 A novel thermophilic planctomycete (strain SVX8T) was isolated from a shallow submarine hydrothermal vent, Vulcano Island, Italy. 26559645 2 58 attach isolated 202:209 arg1 Italy 271:275 Italy 271:275 Italy 271:275 A novel thermophilic planctomycete (strain SVX8T) was isolated from a shallow submarine hydrothermal vent, Vulcano Island, Italy. 26559645 2 58 attach isolated 202:209 arg1 Island 263:268 a shallow submarine hydrothermal vent, Vulcano Island 216:268 Island 263:268 A novel thermophilic planctomycete (strain SVX8T) was isolated from a shallow submarine hydrothermal vent, Vulcano Island, Italy. 26559645 2 58 attach isolated 202:209 arg2 planctomycete 169:181 planctomycete 169:181 planctomycete 169:181 A novel thermophilic planctomycete (strain SVX8T) was isolated from a shallow submarine hydrothermal vent, Vulcano Island, Italy. 26559645 12 59 theme 19992T = VKM 1251:1262 arg1 SVX8T 1237:1241 SVX8T 1237:1241 SVX8T ( = JCM 19992T = VKM B-2881T) 1237:1271 The type strain of Thermostilla marina is SVX8T ( = JCM 19992T = VKM B-2881T). 26559645 12 59 theme 19992T = VKM 1251:1262 arg1 B-2881T 1264:1270  = JCM 19992T = VKM B-2881T 1244:1270  = JCM 19992T = VKM B-2881T 1244:1270 The type strain of Thermostilla marina is SVX8T ( = JCM 19992T = VKM B-2881T). 26559645 2 60 theme submarine 226:234 arg1 Italy 271:275 Italy 271:275 Italy 271:275 A novel thermophilic planctomycete (strain SVX8T) was isolated from a shallow submarine hydrothermal vent, Vulcano Island, Italy. 26559645 2 60 theme submarine 226:234 arg1 Island 263:268 a shallow submarine hydrothermal vent, Vulcano Island 216:268 Island 263:268 A novel thermophilic planctomycete (strain SVX8T) was isolated from a shallow submarine hydrothermal vent, Vulcano Island, Italy. 26559645 12 61 theme  = JCM 1244:1249 arg1 SVX8T 1237:1241 SVX8T 1237:1241 SVX8T ( = JCM 19992T = VKM B-2881T) 1237:1271 The type strain of Thermostilla marina is SVX8T ( = JCM 19992T = VKM B-2881T). 26559645 12 61 theme  = JCM 1244:1249 arg1 B-2881T 1264:1270  = JCM 19992T = VKM B-2881T 1244:1270  = JCM 19992T = VKM B-2881T 1244:1270 The type strain of Thermostilla marina is SVX8T ( = JCM 19992T = VKM B-2881T). 26559645 9 62 theme G+C 898:900 arg1 content 902:908 The G+C content 894:908 The G+C content of the DNA of strain SVX8T 894:935 The G+C content of the DNA of strain SVX8T was 58.5 mol%. 26559645 9 62 theme G+C 898:900 arg1 % 949:949 58.5 mol% 941:949 58.5 mol% 941:949 The G+C content of the DNA of strain SVX8T was 58.5 mol%. 26013532 2 0 theme endosome 368:375 arg1 markers 386:392 trans-Golgi network/early endosome (TGN/EE) markers 342:392 trans-Golgi network/early endosome (TGN/EE) markers 342:392 We previously identified an Arabidopsis thaliana mutant in which a plasma membrane (PM) marker GFP-NIP5;1 and trans-Golgi network/early endosome (TGN/EE) markers were accumulated in intracellular aggregates in epidermal cells of the root elongation zone. 26013532 8 1 theme endomembrane 1640:1651 arg1 organization 1653:1664 endomembrane organization 1640:1664 endomembrane organization 1640:1664 The abnormal localizations of these markers in the uge4 mutant differed from the effects of inhibitors of actin and microtubule polymerization, although they also affected endomembrane organization. 26013532 3 2 theme UGE4 554:557 arg1 bulgar 597:602 UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1 529:604 UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1 529:604 The mutant was identified as an allele of UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1, which was previously described as a mutant with swollen root epidermal cells and has an altered sugar composition in cell wall polysaccharides. 26013532 3 2 theme UGE4 554:557 arg1 mutant 643:648 a mutant 641:648 a mutant with swollen root epidermal cells 641:682 The mutant was identified as an allele of UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1, which was previously described as a mutant with swollen root epidermal cells and has an altered sugar composition in cell wall polysaccharides. 26013532 3 2 theme UGE4 554:557 arg1 composition 709:719 an altered sugar composition 692:719 an altered sugar composition in cell wall polysaccharides 692:748 The mutant was identified as an allele of UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1, which was previously described as a mutant with swollen root epidermal cells and has an altered sugar composition in cell wall polysaccharides. 26013532 9 3 theme electron 1680:1687 arg1 microscopy 1689:1698 electron microscopy 1680:1698 electron microscopy analysis 1680:1707 Furthermore, electron microscopy analysis revealed accumulation of abnormal high-electron-density vesicles in elongating epidermal cells. 26013532 6 4 theme high-B 1186:1191 arg1 supply 1193:1198 high-B supply 1186:1198 high-B supply 1186:1198 Here, we further investigated the nature of the aggregates using various markers of endomembrane compartments and BOR1-GFP, which traffics from PM to vacuole in response to high-B supply. 26013532 3 5 theme altered 695:701 arg1 bulgar 597:602 UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1 529:604 UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1 529:604 The mutant was identified as an allele of UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1, which was previously described as a mutant with swollen root epidermal cells and has an altered sugar composition in cell wall polysaccharides. 26013532 3 5 theme altered 695:701 arg1 mutant 643:648 a mutant 641:648 a mutant with swollen root epidermal cells 641:682 The mutant was identified as an allele of UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1, which was previously described as a mutant with swollen root epidermal cells and has an altered sugar composition in cell wall polysaccharides. 26013532 3 5 theme altered 695:701 arg1 composition 709:719 an altered sugar composition 692:719 an altered sugar composition in cell wall polysaccharides 692:748 The mutant was identified as an allele of UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1, which was previously described as a mutant with swollen root epidermal cells and has an altered sugar composition in cell wall polysaccharides. 26013532 2 6 theme plasma 299:304 arg1 PM 316:317 PM 316:317 PM 316:317 We previously identified an Arabidopsis thaliana mutant in which a plasma membrane (PM) marker GFP-NIP5;1 and trans-Golgi network/early endosome (TGN/EE) markers were accumulated in intracellular aggregates in epidermal cells of the root elongation zone. 26013532 2 6 theme plasma 299:304 arg1 membrane 306:313 plasma membrane 299:313 a plasma membrane (PM) marker GFP-NIP5 297:334 We previously identified an Arabidopsis thaliana mutant in which a plasma membrane (PM) marker GFP-NIP5;1 and trans-Golgi network/early endosome (TGN/EE) markers were accumulated in intracellular aggregates in epidermal cells of the root elongation zone. 26013532 3 7 theme defective 570:578 arg1 bulgar 597:602 UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1 529:604 UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1 529:604 The mutant was identified as an allele of UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1, which was previously described as a mutant with swollen root epidermal cells and has an altered sugar composition in cell wall polysaccharides. 26013532 3 7 theme defective 570:578 arg1 mutant 643:648 a mutant 641:648 a mutant with swollen root epidermal cells 641:682 The mutant was identified as an allele of UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1, which was previously described as a mutant with swollen root epidermal cells and has an altered sugar composition in cell wall polysaccharides. 26013532 3 7 theme defective 570:578 arg1 composition 709:719 an altered sugar composition 692:719 an altered sugar composition in cell wall polysaccharides 692:748 The mutant was identified as an allele of UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1, which was previously described as a mutant with swollen root epidermal cells and has an altered sugar composition in cell wall polysaccharides. 26013532 1 8 theme cell 215:218 arg1 physiology 220:229 cell physiology 215:229 cell physiology 215:229 Endomembrane organization is essential for cell physiology. 26013532 3 9 theme cell 724:727 arg1 polysaccharides 734:748 cell wall polysaccharides 724:748 cell wall polysaccharides 724:748 The mutant was identified as an allele of UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1, which was previously described as a mutant with swollen root epidermal cells and has an altered sugar composition in cell wall polysaccharides. 26013532 0 10 theme Arabidopsis 129:139 arg1 cells 165:169 Arabidopsis thaliana root epidermal cells 129:169 Arabidopsis thaliana root epidermal cells 129:169 UDP-D-galactose synthesis by UDP-glucose 4-epimerase 4 is required for organization of the trans-Golgi network/early endosome in Arabidopsis thaliana root epidermal cells. 26013532 3 11 theme /root 559:563 arg1 bulgar 597:602 UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1 529:604 UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1 529:604 The mutant was identified as an allele of UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1, which was previously described as a mutant with swollen root epidermal cells and has an altered sugar composition in cell wall polysaccharides. 26013532 3 11 theme /root 559:563 arg1 mutant 643:648 a mutant 641:648 a mutant with swollen root epidermal cells 641:682 The mutant was identified as an allele of UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1, which was previously described as a mutant with swollen root epidermal cells and has an altered sugar composition in cell wall polysaccharides. 26013532 3 11 theme /root 559:563 arg1 composition 709:719 an altered sugar composition 692:719 an altered sugar composition in cell wall polysaccharides 692:748 The mutant was identified as an allele of UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1, which was previously described as a mutant with swollen root epidermal cells and has an altered sugar composition in cell wall polysaccharides. 26013532 9 12 theme abnormal 1734:1741 arg1 vesicles 1765:1772 abnormal high-electron-density vesicles 1734:1772 abnormal high-electron-density vesicles 1734:1772 Furthermore, electron microscopy analysis revealed accumulation of abnormal high-electron-density vesicles in elongating epidermal cells. 26013532 7 13 theme vacuolar 1387:1394 arg1 membrane 1396:1403 the vacuolar membrane 1383:1403 the vacuolar membrane 1383:1403 The markers of multi-vesicular bodies/late endosomes (MVB/LEs) and BOR1-GFP were strongly accumulated in the intracellular aggregates, while those of the endoplasmic reticulum (ER), the vacuolar membrane, and the Golgi were only slightly affected in the uge4 mutant. 26013532 12 14 theme UDP-D-galactose 2132:2146 arg1 synthesis 2148:2156 UDP-D-galactose synthesis 2132:2156 UDP-D-galactose synthesis by UGE4 2132:2164 Together, our data indicate the importance of UDP-D-galactose synthesis by UGE4 for the organization and function of endomembranes, especially TGN/EEs, which are a sorting station of the secretory and vacuolar pathways. 26013532 0 15 theme root 150:153 arg1 cells 165:169 Arabidopsis thaliana root epidermal cells 129:169 Arabidopsis thaliana root epidermal cells 129:169 UDP-D-galactose synthesis by UDP-glucose 4-epimerase 4 is required for organization of the trans-Golgi network/early endosome in Arabidopsis thaliana root epidermal cells. 26013532 2 16 theme Arabidopsis 260:270 arg1 mutant 281:286 an Arabidopsis thaliana mutant 257:286 an Arabidopsis thaliana mutant in which a plasma membrane (PM) marker GFP-NIP5;1 and trans-Golgi network/early endosome (TGN/EE) markers were accumulated in intracellular aggregates in epidermal cells of the root elongation zone 257:484 We previously identified an Arabidopsis thaliana mutant in which a plasma membrane (PM) marker GFP-NIP5;1 and trans-Golgi network/early endosome (TGN/EE) markers were accumulated in intracellular aggregates in epidermal cells of the root elongation zone. 26013532 9 17 theme vesicles 1765:1772 arg1 accumulation 1718:1729 accumulation 1718:1729 accumulation of abnormal high-electron-density vesicles in elongating epidermal cells 1718:1802 Furthermore, electron microscopy analysis revealed accumulation of abnormal high-electron-density vesicles in elongating epidermal cells. 26013532 3 18 theme epidermal 587:595 arg1 bulgar 597:602 UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1 529:604 UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1 529:604 The mutant was identified as an allele of UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1, which was previously described as a mutant with swollen root epidermal cells and has an altered sugar composition in cell wall polysaccharides. 26013532 3 18 theme epidermal 587:595 arg1 mutant 643:648 a mutant 641:648 a mutant with swollen root epidermal cells 641:682 The mutant was identified as an allele of UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1, which was previously described as a mutant with swollen root epidermal cells and has an altered sugar composition in cell wall polysaccharides. 26013532 3 18 theme epidermal 587:595 arg1 composition 709:719 an altered sugar composition 692:719 an altered sugar composition in cell wall polysaccharides 692:748 The mutant was identified as an allele of UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1, which was previously described as a mutant with swollen root epidermal cells and has an altered sugar composition in cell wall polysaccharides. 26013532 9 19 theme elongating 1777:1786 arg1 cells 1798:1802 elongating epidermal cells 1777:1802 elongating epidermal cells 1777:1802 Furthermore, electron microscopy analysis revealed accumulation of abnormal high-electron-density vesicles in elongating epidermal cells. 26013532 10 20 theme ADP-ribosylation 1894:1909 arg1 factor 1911:1916 ADP-ribosylation factor 1 1894:1918 ADP-ribosylation factor 1 1894:1918 The abnormal vesicles were often associated or interconnected with TGN/EEs and contained ADP-ribosylation factor 1, which is usually localized to the Golgi and the TGN/EEs. 26013532 8 21 theme abnormal 1472:1479 arg1 localizations 1481:1493 The abnormal localizations 1468:1493 The abnormal localizations of these markers in the uge4 mutant 1468:1529 The abnormal localizations of these markers in the uge4 mutant differed from the effects of inhibitors of actin and microtubule polymerization, although they also affected endomembrane organization. 26013532 11 22 theme ER 2015:2016 arg1 structures 1997:2006 structures 1997:2006 structures of the ER, Golgi apparatus, and MVB/LEs 1997:2046 On the other hand, structures of the ER, Golgi apparatus, and MVB/LEs were apparently normal in uge4 cells. 26013532 5 23 theme UDP-D-galactose 900:914 arg1 synthesis 916:924 UDP-D-galactose synthesis 900:924 UDP-D-galactose synthesis by UGE4 900:932 These results suggested that UDP-D-galactose synthesis by UGE4 is important for endomembrane organization in addition to cell wall structure. 26013532 12 24 theme pathways 2296:2303 arg1 function 2191:2198 function 2191:2198 function 2191:2198 Together, our data indicate the importance of UDP-D-galactose synthesis by UGE4 for the organization and function of endomembranes, especially TGN/EEs, which are a sorting station of the secretory and vacuolar pathways. 26013532 12 24 theme pathways 2296:2303 arg1 station 2258:2264 a sorting station 2248:2264 a sorting station of the secretory and vacuolar pathways 2248:2303 Together, our data indicate the importance of UDP-D-galactose synthesis by UGE4 for the organization and function of endomembranes, especially TGN/EEs, which are a sorting station of the secretory and vacuolar pathways. 26013532 12 24 theme pathways 2296:2303 arg1 organization 2174:2185 organization 2174:2185 organization 2174:2185 Together, our data indicate the importance of UDP-D-galactose synthesis by UGE4 for the organization and function of endomembranes, especially TGN/EEs, which are a sorting station of the secretory and vacuolar pathways. 26013532 7 25 theme endosomes 1244:1252 arg1 markers 1205:1211 The markers 1201:1211 The markers of multi-vesicular bodies/late endosomes (MVB/LEs) and BOR1-GFP 1201:1275 The markers of multi-vesicular bodies/late endosomes (MVB/LEs) and BOR1-GFP were strongly accumulated in the intracellular aggregates, while those of the endoplasmic reticulum (ER), the vacuolar membrane, and the Golgi were only slightly affected in the uge4 mutant. 26013532 0 26 dep Arabidopsis 129:139 arg1 thaliana 141:148 thaliana 141:148 thaliana 141:148 UDP-D-galactose synthesis by UDP-glucose 4-epimerase 4 is required for organization of the trans-Golgi network/early endosome in Arabidopsis thaliana root epidermal cells. 26013532 8 27 theme markers 1504:1510 arg1 localizations 1481:1493 The abnormal localizations 1468:1493 The abnormal localizations of these markers in the uge4 mutant 1468:1529 The abnormal localizations of these markers in the uge4 mutant differed from the effects of inhibitors of actin and microtubule polymerization, although they also affected endomembrane organization. 26013532 12 28 theme sorting 2250:2256 arg1 function 2191:2198 function 2191:2198 function 2191:2198 Together, our data indicate the importance of UDP-D-galactose synthesis by UGE4 for the organization and function of endomembranes, especially TGN/EEs, which are a sorting station of the secretory and vacuolar pathways. 26013532 12 28 theme sorting 2250:2256 arg1 station 2258:2264 a sorting station 2248:2264 a sorting station of the secretory and vacuolar pathways 2248:2303 Together, our data indicate the importance of UDP-D-galactose synthesis by UGE4 for the organization and function of endomembranes, especially TGN/EEs, which are a sorting station of the secretory and vacuolar pathways. 26013532 12 28 theme sorting 2250:2256 arg1 organization 2174:2185 organization 2174:2185 organization 2174:2185 Together, our data indicate the importance of UDP-D-galactose synthesis by UGE4 for the organization and function of endomembranes, especially TGN/EEs, which are a sorting station of the secretory and vacuolar pathways. 26013532 0 29 theme trans-Golgi 91:101 arg1 endosome 117:124 the trans-Golgi network/early endosome 87:124 the trans-Golgi network/early endosome 87:124 UDP-D-galactose synthesis by UDP-glucose 4-epimerase 4 is required for organization of the trans-Golgi network/early endosome in Arabidopsis thaliana root epidermal cells. 26013532 11 30 theme MVB/LEs 2040:2046 arg1 structures 1997:2006 structures 1997:2006 structures of the ER, Golgi apparatus, and MVB/LEs 1997:2046 On the other hand, structures of the ER, Golgi apparatus, and MVB/LEs were apparently normal in uge4 cells. 26013532 5 31 theme cell 992:995 arg1 structure 1002:1010 cell wall structure 992:1010 cell wall structure 992:1010 These results suggested that UDP-D-galactose synthesis by UGE4 is important for endomembrane organization in addition to cell wall structure. 26013532 0 32 theme endosome 117:124 arg1 organization 71:82 organization 71:82 organization of the trans-Golgi network/early endosome in Arabidopsis thaliana root epidermal cells 71:169 UDP-D-galactose synthesis by UDP-glucose 4-epimerase 4 is required for organization of the trans-Golgi network/early endosome in Arabidopsis thaliana root epidermal cells. 26013532 7 33 theme endoplasmic 1355:1365 arg1 ER 1378:1379 ER 1378:1379 ER 1378:1379 The markers of multi-vesicular bodies/late endosomes (MVB/LEs) and BOR1-GFP were strongly accumulated in the intracellular aggregates, while those of the endoplasmic reticulum (ER), the vacuolar membrane, and the Golgi were only slightly affected in the uge4 mutant. 26013532 7 33 theme endoplasmic 1355:1365 arg1 reticulum 1367:1375 the endoplasmic reticulum 1351:1375 the endoplasmic reticulum (ER) 1351:1380 The markers of multi-vesicular bodies/late endosomes (MVB/LEs) and BOR1-GFP were strongly accumulated in the intracellular aggregates, while those of the endoplasmic reticulum (ER), the vacuolar membrane, and the Golgi were only slightly affected in the uge4 mutant. 26013532 2 34 theme root 465:468 arg1 zone 481:484 the root elongation zone 461:484 the root elongation zone 461:484 We previously identified an Arabidopsis thaliana mutant in which a plasma membrane (PM) marker GFP-NIP5;1 and trans-Golgi network/early endosome (TGN/EE) markers were accumulated in intracellular aggregates in epidermal cells of the root elongation zone. 26013532 0 35 theme UDP-D-galactose 0:14 arg1 synthesis 16:24 UDP-D-galactose synthesis 0:24 UDP-D-galactose synthesis by UDP-glucose 4-epimerase 4 0:53 UDP-D-galactose synthesis by UDP-glucose 4-epimerase 4 is required for organization of the trans-Golgi network/early endosome in Arabidopsis thaliana root epidermal cells. 26013532 6 36 theme various 1078:1084 arg1 markers 1086:1092 various markers 1078:1092 various markers 1078:1092 Here, we further investigated the nature of the aggregates using various markers of endomembrane compartments and BOR1-GFP, which traffics from PM to vacuole in response to high-B supply. 26013532 2 37 theme epidermal 442:450 arg1 cells 452:456 epidermal cells 442:456 epidermal cells of the root elongation zone 442:484 We previously identified an Arabidopsis thaliana mutant in which a plasma membrane (PM) marker GFP-NIP5;1 and trans-Golgi network/early endosome (TGN/EE) markers were accumulated in intracellular aggregates in epidermal cells of the root elongation zone. 26013532 3 38 theme epimerase 541:549 arg1 bulgar 597:602 UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1 529:604 UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1 529:604 The mutant was identified as an allele of UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1, which was previously described as a mutant with swollen root epidermal cells and has an altered sugar composition in cell wall polysaccharides. 26013532 3 38 theme epimerase 541:549 arg1 mutant 643:648 a mutant 641:648 a mutant with swollen root epidermal cells 641:682 The mutant was identified as an allele of UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1, which was previously described as a mutant with swollen root epidermal cells and has an altered sugar composition in cell wall polysaccharides. 26013532 3 38 theme epimerase 541:549 arg1 composition 709:719 an altered sugar composition 692:719 an altered sugar composition in cell wall polysaccharides 692:748 The mutant was identified as an allele of UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1, which was previously described as a mutant with swollen root epidermal cells and has an altered sugar composition in cell wall polysaccharides. 26013532 6 39 theme aggregates 1061:1070 arg1 nature 1047:1052 the nature 1043:1052 the nature of the aggregates 1043:1070 Here, we further investigated the nature of the aggregates using various markers of endomembrane compartments and BOR1-GFP, which traffics from PM to vacuole in response to high-B supply. 26013532 12 40 theme endomembranes 2203:2215 arg1 TGN/EEs 2229:2235 TGN/EEs 2229:2235 TGN/EEs 2229:2235 Together, our data indicate the importance of UDP-D-galactose synthesis by UGE4 for the organization and function of endomembranes, especially TGN/EEs, which are a sorting station of the secretory and vacuolar pathways. 26013532 12 40 theme endomembranes 2203:2215 arg1 function 2191:2198 function 2191:2198 function 2191:2198 Together, our data indicate the importance of UDP-D-galactose synthesis by UGE4 for the organization and function of endomembranes, especially TGN/EEs, which are a sorting station of the secretory and vacuolar pathways. 26013532 12 40 theme endomembranes 2203:2215 arg1 station 2258:2264 a sorting station 2248:2264 a sorting station of the secretory and vacuolar pathways 2248:2303 Together, our data indicate the importance of UDP-D-galactose synthesis by UGE4 for the organization and function of endomembranes, especially TGN/EEs, which are a sorting station of the secretory and vacuolar pathways. 26013532 12 40 theme endomembranes 2203:2215 arg1 organization 2174:2185 organization 2174:2185 organization 2174:2185 Together, our data indicate the importance of UDP-D-galactose synthesis by UGE4 for the organization and function of endomembranes, especially TGN/EEs, which are a sorting station of the secretory and vacuolar pathways. 26013532 2 41 theme zone 481:484 arg1 cells 452:456 epidermal cells 442:456 epidermal cells of the root elongation zone 442:484 We previously identified an Arabidopsis thaliana mutant in which a plasma membrane (PM) marker GFP-NIP5;1 and trans-Golgi network/early endosome (TGN/EE) markers were accumulated in intracellular aggregates in epidermal cells of the root elongation zone. 26013532 8 42 theme inhibitors 1560:1569 arg1 effects 1549:1555 the effects 1545:1555 the effects of inhibitors of actin and microtubule polymerization 1545:1609 The abnormal localizations of these markers in the uge4 mutant differed from the effects of inhibitors of actin and microtubule polymerization, although they also affected endomembrane organization. 26013532 2 43 theme network/early 354:366 arg1 markers 386:392 trans-Golgi network/early endosome (TGN/EE) markers 342:392 trans-Golgi network/early endosome (TGN/EE) markers 342:392 We previously identified an Arabidopsis thaliana mutant in which a plasma membrane (PM) marker GFP-NIP5;1 and trans-Golgi network/early endosome (TGN/EE) markers were accumulated in intracellular aggregates in epidermal cells of the root elongation zone. 26013532 9 44 theme microscopy 1689:1698 arg1 analysis 1700:1707 electron microscopy analysis 1680:1707 electron microscopy analysis 1680:1707 Furthermore, electron microscopy analysis revealed accumulation of abnormal high-electron-density vesicles in elongating epidermal cells. 26013532 8 45 theme actin 1574:1578 arg1 inhibitors 1560:1569 inhibitors 1560:1569 inhibitors of actin and microtubule polymerization 1560:1609 The abnormal localizations of these markers in the uge4 mutant differed from the effects of inhibitors of actin and microtubule polymerization, although they also affected endomembrane organization. 26013532 3 46 theme epidermal 668:676 arg1 cells 678:682 swollen root epidermal cells 655:682 swollen root epidermal cells 655:682 The mutant was identified as an allele of UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1, which was previously described as a mutant with swollen root epidermal cells and has an altered sugar composition in cell wall polysaccharides. 26013532 4 47 theme aggregate 788:796 arg1 formation 798:806 aggregate formation 788:806 aggregate formation 788:806 Importantly, these defects including aggregate formation were restored by supplementation of D-galactose in the medium. 26013532 2 48 from aggregates 428:437 arg1 cells 452:456 epidermal cells 442:456 epidermal cells of the root elongation zone 442:484 We previously identified an Arabidopsis thaliana mutant in which a plasma membrane (PM) marker GFP-NIP5;1 and trans-Golgi network/early endosome (TGN/EE) markers were accumulated in intracellular aggregates in epidermal cells of the root elongation zone. 26013532 11 49 from normal 2064:2069 arg1 cells 2079:2083 uge4 cells 2074:2083 uge4 cells 2074:2083 On the other hand, structures of the ER, Golgi apparatus, and MVB/LEs were apparently normal in uge4 cells. 26013532 8 50 theme microtubule 1584:1594 arg1 polymerization 1596:1609 microtubule polymerization 1584:1609 microtubule polymerization 1584:1609 The abnormal localizations of these markers in the uge4 mutant differed from the effects of inhibitors of actin and microtubule polymerization, although they also affected endomembrane organization. 26013532 3 51 theme swollen 655:661 arg1 cells 678:682 swollen root epidermal cells 655:682 swollen root epidermal cells 655:682 The mutant was identified as an allele of UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1, which was previously described as a mutant with swollen root epidermal cells and has an altered sugar composition in cell wall polysaccharides. 26013532 6 52 theme BOR1-GFP 1127:1134 arg1 markers 1086:1092 various markers 1078:1092 various markers 1078:1092 Here, we further investigated the nature of the aggregates using various markers of endomembrane compartments and BOR1-GFP, which traffics from PM to vacuole in response to high-B supply. 26013532 10 53 dep Golgi 1955:1959 arg1 the 1951:1953 the 1951:1953 the 1951:1953 The abnormal vesicles were often associated or interconnected with TGN/EEs and contained ADP-ribosylation factor 1, which is usually localized to the Golgi and the TGN/EEs. 26013532 6 54 theme compartments 1110:1121 arg1 markers 1086:1092 various markers 1078:1092 various markers 1078:1092 Here, we further investigated the nature of the aggregates using various markers of endomembrane compartments and BOR1-GFP, which traffics from PM to vacuole in response to high-B supply. 26013532 10 55 theme abnormal 1809:1816 arg1 vesicles 1818:1825 The abnormal vesicles 1805:1825 The abnormal vesicles 1805:1825 The abnormal vesicles were often associated or interconnected with TGN/EEs and contained ADP-ribosylation factor 1, which is usually localized to the Golgi and the TGN/EEs. 26013532 10 55 theme abnormal 1809:1816 arg1 associated 1838:1847 associated 1838:1847 associated 1838:1847 The abnormal vesicles were often associated or interconnected with TGN/EEs and contained ADP-ribosylation factor 1, which is usually localized to the Golgi and the TGN/EEs. 26013532 7 56 theme uge4 1455:1458 arg1 mutant 1460:1465 the uge4 mutant 1451:1465 the uge4 mutant 1451:1465 The markers of multi-vesicular bodies/late endosomes (MVB/LEs) and BOR1-GFP were strongly accumulated in the intracellular aggregates, while those of the endoplasmic reticulum (ER), the vacuolar membrane, and the Golgi were only slightly affected in the uge4 mutant. 26013532 2 57 theme membrane 306:313 arg1 GFP-NIP5 327:334 a plasma membrane (PM) marker GFP-NIP5 297:334 a plasma membrane (PM) marker GFP-NIP5 297:334 We previously identified an Arabidopsis thaliana mutant in which a plasma membrane (PM) marker GFP-NIP5;1 and trans-Golgi network/early endosome (TGN/EE) markers were accumulated in intracellular aggregates in epidermal cells of the root elongation zone. 26013532 4 58 theme D-galactose 844:854 arg1 supplementation 825:839 supplementation 825:839 supplementation of D-galactose in the medium 825:868 Importantly, these defects including aggregate formation were restored by supplementation of D-galactose in the medium. 26013532 12 59 theme synthesis 2148:2156 arg1 importance 2118:2127 the importance 2114:2127 the importance of UDP-D-galactose synthesis by UGE4 for the organization and function of endomembranes, especially TGN/EEs, which are a sorting station of the secretory and vacuolar pathways 2114:2303 Together, our data indicate the importance of UDP-D-galactose synthesis by UGE4 for the organization and function of endomembranes, especially TGN/EEs, which are a sorting station of the secretory and vacuolar pathways. 26013532 3 60 theme sugar 703:707 arg1 bulgar 597:602 UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1 529:604 UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1 529:604 The mutant was identified as an allele of UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1, which was previously described as a mutant with swollen root epidermal cells and has an altered sugar composition in cell wall polysaccharides. 26013532 3 60 theme sugar 703:707 arg1 mutant 643:648 a mutant 641:648 a mutant with swollen root epidermal cells 641:682 The mutant was identified as an allele of UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1, which was previously described as a mutant with swollen root epidermal cells and has an altered sugar composition in cell wall polysaccharides. 26013532 3 60 theme sugar 703:707 arg1 composition 709:719 an altered sugar composition 692:719 an altered sugar composition in cell wall polysaccharides 692:748 The mutant was identified as an allele of UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1, which was previously described as a mutant with swollen root epidermal cells and has an altered sugar composition in cell wall polysaccharides. 26013532 3 61 theme hair 565:568 arg1 bulgar 597:602 UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1 529:604 UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1 529:604 The mutant was identified as an allele of UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1, which was previously described as a mutant with swollen root epidermal cells and has an altered sugar composition in cell wall polysaccharides. 26013532 3 61 theme hair 565:568 arg1 mutant 643:648 a mutant 641:648 a mutant with swollen root epidermal cells 641:682 The mutant was identified as an allele of UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1, which was previously described as a mutant with swollen root epidermal cells and has an altered sugar composition in cell wall polysaccharides. 26013532 3 61 theme hair 565:568 arg1 composition 709:719 an altered sugar composition 692:719 an altered sugar composition in cell wall polysaccharides 692:748 The mutant was identified as an allele of UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1, which was previously described as a mutant with swollen root epidermal cells and has an altered sugar composition in cell wall polysaccharides. 26013532 12 62 dep organization 2174:2185 arg1 the 2170:2172 the 2170:2172 the 2170:2172 Together, our data indicate the importance of UDP-D-galactose synthesis by UGE4 for the organization and function of endomembranes, especially TGN/EEs, which are a sorting station of the secretory and vacuolar pathways. 26013532 3 63 from composition 709:719 arg1 polysaccharides 734:748 cell wall polysaccharides 724:748 cell wall polysaccharides 724:748 The mutant was identified as an allele of UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1, which was previously described as a mutant with swollen root epidermal cells and has an altered sugar composition in cell wall polysaccharides. 26013532 2 64 theme marker 320:325 arg1 GFP-NIP5 327:334 a plasma membrane (PM) marker GFP-NIP5 297:334 a plasma membrane (PM) marker GFP-NIP5 297:334 We previously identified an Arabidopsis thaliana mutant in which a plasma membrane (PM) marker GFP-NIP5;1 and trans-Golgi network/early endosome (TGN/EE) markers were accumulated in intracellular aggregates in epidermal cells of the root elongation zone. 26013532 3 65 theme wall 729:732 arg1 polysaccharides 734:748 cell wall polysaccharides 724:748 cell wall polysaccharides 724:748 The mutant was identified as an allele of UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1, which was previously described as a mutant with swollen root epidermal cells and has an altered sugar composition in cell wall polysaccharides. 26013532 0 66 theme epidermal 155:163 arg1 cells 165:169 Arabidopsis thaliana root epidermal cells 129:169 Arabidopsis thaliana root epidermal cells 129:169 UDP-D-galactose synthesis by UDP-glucose 4-epimerase 4 is required for organization of the trans-Golgi network/early endosome in Arabidopsis thaliana root epidermal cells. 26013532 3 67 theme bulgar 597:602 arg1 allele 519:524 an allele 516:524 an allele of UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1, which was previously described as a mutant with swollen root epidermal cells and has an altered sugar composition in cell wall polysaccharides 516:748 The mutant was identified as an allele of UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1, which was previously described as a mutant with swollen root epidermal cells and has an altered sugar composition in cell wall polysaccharides. 26013532 3 67 theme bulgar 597:602 arg1 mutant 491:496 The mutant 487:496 The mutant 487:496 The mutant was identified as an allele of UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1, which was previously described as a mutant with swollen root epidermal cells and has an altered sugar composition in cell wall polysaccharides. 26013532 3 68 with mutant 643:648 arg1 cells 678:682 swollen root epidermal cells 655:682 swollen root epidermal cells 655:682 The mutant was identified as an allele of UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1, which was previously described as a mutant with swollen root epidermal cells and has an altered sugar composition in cell wall polysaccharides. 26013532 9 69 theme high-electron-density 1743:1763 arg1 vesicles 1765:1772 abnormal high-electron-density vesicles 1734:1772 abnormal high-electron-density vesicles 1734:1772 Furthermore, electron microscopy analysis revealed accumulation of abnormal high-electron-density vesicles in elongating epidermal cells. 26013532 0 70 from organization 71:82 arg1 cells 165:169 Arabidopsis thaliana root epidermal cells 129:169 Arabidopsis thaliana root epidermal cells 129:169 UDP-D-galactose synthesis by UDP-glucose 4-epimerase 4 is required for organization of the trans-Golgi network/early endosome in Arabidopsis thaliana root epidermal cells. 26013532 8 71 from localizations 1481:1493 arg1 mutant 1524:1529 the uge4 mutant 1515:1529 the uge4 mutant 1515:1529 The abnormal localizations of these markers in the uge4 mutant differed from the effects of inhibitors of actin and microtubule polymerization, although they also affected endomembrane organization. 26013532 3 72 theme 1/root 580:585 arg1 bulgar 597:602 UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1 529:604 UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1 529:604 The mutant was identified as an allele of UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1, which was previously described as a mutant with swollen root epidermal cells and has an altered sugar composition in cell wall polysaccharides. 26013532 3 72 theme 1/root 580:585 arg1 mutant 643:648 a mutant 641:648 a mutant with swollen root epidermal cells 641:682 The mutant was identified as an allele of UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1, which was previously described as a mutant with swollen root epidermal cells and has an altered sugar composition in cell wall polysaccharides. 26013532 3 72 theme 1/root 580:585 arg1 composition 709:719 an altered sugar composition 692:719 an altered sugar composition in cell wall polysaccharides 692:748 The mutant was identified as an allele of UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1, which was previously described as a mutant with swollen root epidermal cells and has an altered sugar composition in cell wall polysaccharides. 26013532 4 73 from supplementation 825:839 arg1 medium 863:868 the medium 859:868 the medium 859:868 Importantly, these defects including aggregate formation were restored by supplementation of D-galactose in the medium. 26013532 11 74 theme apparatus 2025:2033 arg1 structures 1997:2006 structures 1997:2006 structures of the ER, Golgi apparatus, and MVB/LEs 1997:2046 On the other hand, structures of the ER, Golgi apparatus, and MVB/LEs were apparently normal in uge4 cells. 26013532 9 75 theme epidermal 1788:1796 arg1 cells 1798:1802 elongating epidermal cells 1777:1802 elongating epidermal cells 1777:1802 Furthermore, electron microscopy analysis revealed accumulation of abnormal high-electron-density vesicles in elongating epidermal cells. 26013532 11 76 theme Golgi 2019:2023 arg1 apparatus 2025:2033 Golgi apparatus 2019:2033 Golgi apparatus 2019:2033 On the other hand, structures of the ER, Golgi apparatus, and MVB/LEs were apparently normal in uge4 cells. 26013532 10 77 with associated 1838:1847 arg1 TGN/EEs 1872:1878 TGN/EEs 1872:1878 TGN/EEs 1872:1878 The abnormal vesicles were often associated or interconnected with TGN/EEs and contained ADP-ribosylation factor 1, which is usually localized to the Golgi and the TGN/EEs. 26013532 7 78 theme multi-vesicular 1216:1230 arg1 endosomes 1244:1252 multi-vesicular bodies/late endosomes 1216:1252 multi-vesicular bodies/late endosomes (MVB/LEs) 1216:1262 The markers of multi-vesicular bodies/late endosomes (MVB/LEs) and BOR1-GFP were strongly accumulated in the intracellular aggregates, while those of the endoplasmic reticulum (ER), the vacuolar membrane, and the Golgi were only slightly affected in the uge4 mutant. 26013532 7 78 theme multi-vesicular 1216:1230 arg1 MVB/LEs 1255:1261 MVB/LEs 1255:1261 MVB/LEs 1255:1261 The markers of multi-vesicular bodies/late endosomes (MVB/LEs) and BOR1-GFP were strongly accumulated in the intracellular aggregates, while those of the endoplasmic reticulum (ER), the vacuolar membrane, and the Golgi were only slightly affected in the uge4 mutant. 26013532 7 79 theme bodies/late 1232:1242 arg1 endosomes 1244:1252 multi-vesicular bodies/late endosomes 1216:1252 multi-vesicular bodies/late endosomes (MVB/LEs) 1216:1262 The markers of multi-vesicular bodies/late endosomes (MVB/LEs) and BOR1-GFP were strongly accumulated in the intracellular aggregates, while those of the endoplasmic reticulum (ER), the vacuolar membrane, and the Golgi were only slightly affected in the uge4 mutant. 26013532 7 79 theme bodies/late 1232:1242 arg1 MVB/LEs 1255:1261 MVB/LEs 1255:1261 MVB/LEs 1255:1261 The markers of multi-vesicular bodies/late endosomes (MVB/LEs) and BOR1-GFP were strongly accumulated in the intracellular aggregates, while those of the endoplasmic reticulum (ER), the vacuolar membrane, and the Golgi were only slightly affected in the uge4 mutant. 26013532 1 80 theme Endomembrane 172:183 arg1 organization 185:196 Endomembrane organization 172:196 Endomembrane organization 172:196 Endomembrane organization is essential for cell physiology. 26013532 12 81 theme secretory 2273:2281 arg1 pathways 2296:2303 the secretory and vacuolar pathways 2269:2303 the secretory and vacuolar pathways 2269:2303 Together, our data indicate the importance of UDP-D-galactose synthesis by UGE4 for the organization and function of endomembranes, especially TGN/EEs, which are a sorting station of the secretory and vacuolar pathways. 26013532 3 82 contain has 688:690 arg1 bulgar 597:602 UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1 529:604 UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1 529:604 The mutant was identified as an allele of UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1, which was previously described as a mutant with swollen root epidermal cells and has an altered sugar composition in cell wall polysaccharides. 26013532 3 82 contain has 688:690 arg1 composition 709:719 an altered sugar composition 692:719 an altered sugar composition in cell wall polysaccharides 692:748 The mutant was identified as an allele of UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1, which was previously described as a mutant with swollen root epidermal cells and has an altered sugar composition in cell wall polysaccharides. 26013532 3 82 contain has 688:690 arg1 mutant 643:648 a mutant 641:648 a mutant with swollen root epidermal cells 641:682 The mutant was identified as an allele of UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1, which was previously described as a mutant with swollen root epidermal cells and has an altered sugar composition in cell wall polysaccharides. 26013532 3 82 contain has 688:690 arg2 composition 709:719 an altered sugar composition 692:719 an altered sugar composition in cell wall polysaccharides 692:748 The mutant was identified as an allele of UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1, which was previously described as a mutant with swollen root epidermal cells and has an altered sugar composition in cell wall polysaccharides. 26013532 3 82 contain has 688:690 arg2 bulgar 597:602 UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1 529:604 UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1 529:604 The mutant was identified as an allele of UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1, which was previously described as a mutant with swollen root epidermal cells and has an altered sugar composition in cell wall polysaccharides. 26013532 3 82 contain has 688:690 arg2 mutant 643:648 a mutant 641:648 a mutant with swollen root epidermal cells 641:682 The mutant was identified as an allele of UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1, which was previously described as a mutant with swollen root epidermal cells and has an altered sugar composition in cell wall polysaccharides. 26013532 11 83 from cells 2079:2083 arg1 normal 2064:2069 normal 2064:2069 normal 2064:2069 On the other hand, structures of the ER, Golgi apparatus, and MVB/LEs were apparently normal in uge4 cells. 26013532 0 84 theme network/early 103:115 arg1 endosome 117:124 the trans-Golgi network/early endosome 87:124 the trans-Golgi network/early endosome 87:124 UDP-D-galactose synthesis by UDP-glucose 4-epimerase 4 is required for organization of the trans-Golgi network/early endosome in Arabidopsis thaliana root epidermal cells. 26013532 9 85 from accumulation 1718:1729 arg1 cells 1798:1802 elongating epidermal cells 1777:1802 elongating epidermal cells 1777:1802 Furthermore, electron microscopy analysis revealed accumulation of abnormal high-electron-density vesicles in elongating epidermal cells. 26013532 8 86 theme uge4 1519:1522 arg1 mutant 1524:1529 the uge4 mutant 1515:1529 the uge4 mutant 1515:1529 The abnormal localizations of these markers in the uge4 mutant differed from the effects of inhibitors of actin and microtubule polymerization, although they also affected endomembrane organization. 26013532 5 87 theme wall 997:1000 arg1 structure 1002:1010 cell wall structure 992:1010 cell wall structure 992:1010 These results suggested that UDP-D-galactose synthesis by UGE4 is important for endomembrane organization in addition to cell wall structure. 26013532 6 88 theme endomembrane 1097:1108 arg1 compartments 1110:1121 endomembrane compartments 1097:1121 endomembrane compartments 1097:1121 Here, we further investigated the nature of the aggregates using various markers of endomembrane compartments and BOR1-GFP, which traffics from PM to vacuole in response to high-B supply. 26013532 12 89 theme vacuolar 2287:2294 arg1 pathways 2296:2303 the secretory and vacuolar pathways 2269:2303 the secretory and vacuolar pathways 2269:2303 Together, our data indicate the importance of UDP-D-galactose synthesis by UGE4 for the organization and function of endomembranes, especially TGN/EEs, which are a sorting station of the secretory and vacuolar pathways. 26013532 5 90 theme endomembrane 951:962 arg1 organization 964:975 endomembrane organization 951:975 endomembrane organization in addition to cell wall structure 951:1010 These results suggested that UDP-D-galactose synthesis by UGE4 is important for endomembrane organization in addition to cell wall structure. 26013532 11 91 theme uge4 2074:2077 arg1 cells 2079:2083 uge4 cells 2074:2083 uge4 cells 2074:2083 On the other hand, structures of the ER, Golgi apparatus, and MVB/LEs were apparently normal in uge4 cells. 26013532 6 92 from vacuole 1163:1169 arg1 response 1174:1181 response 1174:1181 response to high-B supply 1174:1198 Here, we further investigated the nature of the aggregates using various markers of endomembrane compartments and BOR1-GFP, which traffics from PM to vacuole in response to high-B supply. 26013532 0 93 theme UDP-glucose 29:39 arg1 4-epimerase 41:51 UDP-glucose 4-epimerase 4 29:53 UDP-glucose 4-epimerase 4 29:53 UDP-D-galactose synthesis by UDP-glucose 4-epimerase 4 is required for organization of the trans-Golgi network/early endosome in Arabidopsis thaliana root epidermal cells. 26013532 2 94 theme thaliana 272:279 arg1 mutant 281:286 an Arabidopsis thaliana mutant 257:286 an Arabidopsis thaliana mutant in which a plasma membrane (PM) marker GFP-NIP5;1 and trans-Golgi network/early endosome (TGN/EE) markers were accumulated in intracellular aggregates in epidermal cells of the root elongation zone 257:484 We previously identified an Arabidopsis thaliana mutant in which a plasma membrane (PM) marker GFP-NIP5;1 and trans-Golgi network/early endosome (TGN/EE) markers were accumulated in intracellular aggregates in epidermal cells of the root elongation zone. 26013532 11 95 theme other 1985:1989 arg1 hand 1991:1994 the other hand 1981:1994 the other hand 1981:1994 On the other hand, structures of the ER, Golgi apparatus, and MVB/LEs were apparently normal in uge4 cells. 26013532 7 96 theme intracellular 1310:1322 arg1 aggregates 1324:1333 the intracellular aggregates 1306:1333 the intracellular aggregates 1306:1333 The markers of multi-vesicular bodies/late endosomes (MVB/LEs) and BOR1-GFP were strongly accumulated in the intracellular aggregates, while those of the endoplasmic reticulum (ER), the vacuolar membrane, and the Golgi were only slightly affected in the uge4 mutant. 26013532 10 97 contain contained 1884:1892 arg2 factor 1911:1916 ADP-ribosylation factor 1 1894:1918 ADP-ribosylation factor 1 1894:1918 The abnormal vesicles were often associated or interconnected with TGN/EEs and contained ADP-ribosylation factor 1, which is usually localized to the Golgi and the TGN/EEs. 26013532 10 97 contain contained 1884:1892 arg1 vesicles 1818:1825 The abnormal vesicles 1805:1825 The abnormal vesicles 1805:1825 The abnormal vesicles were often associated or interconnected with TGN/EEs and contained ADP-ribosylation factor 1, which is usually localized to the Golgi and the TGN/EEs. 26013532 10 97 contain contained 1884:1892 arg1 associated 1838:1847 associated 1838:1847 associated 1838:1847 The abnormal vesicles were often associated or interconnected with TGN/EEs and contained ADP-ribosylation factor 1, which is usually localized to the Golgi and the TGN/EEs. 26013532 2 98 theme intracellular 414:426 arg1 aggregates 428:437 intracellular aggregates 414:437 intracellular aggregates in epidermal cells of the root elongation zone 414:484 We previously identified an Arabidopsis thaliana mutant in which a plasma membrane (PM) marker GFP-NIP5;1 and trans-Golgi network/early endosome (TGN/EE) markers were accumulated in intracellular aggregates in epidermal cells of the root elongation zone. 26013532 2 99 theme elongation 470:479 arg1 zone 481:484 the root elongation zone 461:484 the root elongation zone 461:484 We previously identified an Arabidopsis thaliana mutant in which a plasma membrane (PM) marker GFP-NIP5;1 and trans-Golgi network/early endosome (TGN/EE) markers were accumulated in intracellular aggregates in epidermal cells of the root elongation zone. 26013532 3 100 theme root 663:666 arg1 cells 678:682 swollen root epidermal cells 655:682 swollen root epidermal cells 655:682 The mutant was identified as an allele of UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1, which was previously described as a mutant with swollen root epidermal cells and has an altered sugar composition in cell wall polysaccharides. 26013532 2 101 theme trans-Golgi 342:352 arg1 markers 386:392 trans-Golgi network/early endosome (TGN/EE) markers 342:392 trans-Golgi network/early endosome (TGN/EE) markers 342:392 We previously identified an Arabidopsis thaliana mutant in which a plasma membrane (PM) marker GFP-NIP5;1 and trans-Golgi network/early endosome (TGN/EE) markers were accumulated in intracellular aggregates in epidermal cells of the root elongation zone. 26013532 8 102 theme polymerization 1596:1609 arg1 inhibitors 1560:1569 inhibitors 1560:1569 inhibitors of actin and microtubule polymerization 1560:1609 The abnormal localizations of these markers in the uge4 mutant differed from the effects of inhibitors of actin and microtubule polymerization, although they also affected endomembrane organization. 26013532 2 103 theme TGN/EE 378:383 arg1 markers 386:392 trans-Golgi network/early endosome (TGN/EE) markers 342:392 trans-Golgi network/early endosome (TGN/EE) markers 342:392 We previously identified an Arabidopsis thaliana mutant in which a plasma membrane (PM) marker GFP-NIP5;1 and trans-Golgi network/early endosome (TGN/EE) markers were accumulated in intracellular aggregates in epidermal cells of the root elongation zone. 26013532 7 104 theme BOR1-GFP 1268:1275 arg1 markers 1205:1211 The markers 1201:1211 The markers of multi-vesicular bodies/late endosomes (MVB/LEs) and BOR1-GFP 1201:1275 The markers of multi-vesicular bodies/late endosomes (MVB/LEs) and BOR1-GFP were strongly accumulated in the intracellular aggregates, while those of the endoplasmic reticulum (ER), the vacuolar membrane, and the Golgi were only slightly affected in the uge4 mutant. 26013532 3 105 theme UDP-glucose 529:539 arg1 bulgar 597:602 UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1 529:604 UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1 529:604 The mutant was identified as an allele of UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1, which was previously described as a mutant with swollen root epidermal cells and has an altered sugar composition in cell wall polysaccharides. 26013532 3 105 theme UDP-glucose 529:539 arg1 mutant 643:648 a mutant 641:648 a mutant with swollen root epidermal cells 641:682 The mutant was identified as an allele of UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1, which was previously described as a mutant with swollen root epidermal cells and has an altered sugar composition in cell wall polysaccharides. 26013532 3 105 theme UDP-glucose 529:539 arg1 composition 709:719 an altered sugar composition 692:719 an altered sugar composition in cell wall polysaccharides 692:748 The mutant was identified as an allele of UDP-glucose epimerase 4 (UGE4)/root hair defective 1/root epidermal bulgar 1, which was previously described as a mutant with swollen root epidermal cells and has an altered sugar composition in cell wall polysaccharides. 28291612 4 0 theme enzyme 704:709 arg1 diversity 764:772 catabolic diversity 754:772 catabolic diversity 754:772 Relations between OBA% and either soil chemical (C and N contents, quality of organic matter via solid-state NMR, pH, CaCO3) or microbial (enzyme activities, basal respiration, biomass and catabolic diversity via BIOLOG) characteristics were described. 28291612 4 0 theme enzyme 704:709 arg1 biomass 742:748 biomass 742:748 biomass 742:748 Relations between OBA% and either soil chemical (C and N contents, quality of organic matter via solid-state NMR, pH, CaCO3) or microbial (enzyme activities, basal respiration, biomass and catabolic diversity via BIOLOG) characteristics were described. 28291612 4 0 theme enzyme 704:709 arg1 activities 711:720 enzyme activities 704:720 enzyme activities 704:720 Relations between OBA% and either soil chemical (C and N contents, quality of organic matter via solid-state NMR, pH, CaCO3) or microbial (enzyme activities, basal respiration, biomass and catabolic diversity via BIOLOG) characteristics were described. 28291612 4 0 theme enzyme 704:709 arg1 respiration 729:739 basal respiration 723:739 basal respiration 723:739 Relations between OBA% and either soil chemical (C and N contents, quality of organic matter via solid-state NMR, pH, CaCO3) or microbial (enzyme activities, basal respiration, biomass and catabolic diversity via BIOLOG) characteristics were described. 28291612 6 1 theme carboxyl 1086:1093 arg1 C 1095:1095 carboxyl C 1086:1095 carboxyl C ratio (characteristic of cutin from Q. ilex tissues) 1086:1148 Catabolic profiles of microbial communities from A-horizon were significantly modulated in Q. ilex and P. halepensis stand by OBA% and alkyl C to carboxyl C ratio (characteristic of cutin from Q. ilex tissues) and in Q. pubescens and P. sylvestris stands, by OBA% and pH. In A-horizon under Q. ilex and P. halepensis stands, linear regressions were found between catabolic diversity, microbial biomass and OBA% suggesting an additive effect. 28291612 2 2 theme sclerophyllous 297:310 arg1 species 312:318 sclerophyllous species 297:318 sclerophyllous species i.e. Quercus ilex mixed with Pinus halepensis Miller or of Q. pubescens mixed with P. sylvestris 297:415 Forests were composed of sclerophyllous species i.e. Quercus ilex mixed with Pinus halepensis Miller or of Q. pubescens mixed with P. sylvestris. 28291612 6 3 theme C 1095:1095 arg1 ratio 1097:1101 carboxyl C ratio 1086:1101 carboxyl C ratio (characteristic of cutin from Q. ilex tissues) 1086:1148 Catabolic profiles of microbial communities from A-horizon were significantly modulated in Q. ilex and P. halepensis stand by OBA% and alkyl C to carboxyl C ratio (characteristic of cutin from Q. ilex tissues) and in Q. pubescens and P. sylvestris stands, by OBA% and pH. In A-horizon under Q. ilex and P. halepensis stands, linear regressions were found between catabolic diversity, microbial biomass and OBA% suggesting an additive effect. 28291612 6 4 theme catabolic 1303:1311 arg1 diversity 1313:1321 catabolic diversity 1303:1321 catabolic diversity 1303:1321 Catabolic profiles of microbial communities from A-horizon were significantly modulated in Q. ilex and P. halepensis stand by OBA% and alkyl C to carboxyl C ratio (characteristic of cutin from Q. ilex tissues) and in Q. pubescens and P. sylvestris stands, by OBA% and pH. In A-horizon under Q. ilex and P. halepensis stands, linear regressions were found between catabolic diversity, microbial biomass and OBA% suggesting an additive effect. 28291612 1 5 theme OBA 225:227 arg1 % 222:222 using relative Oak Basal Area % 192:222 using relative Oak Basal Area % 192:222 This study investigated how oak abundance in pine stands (using relative Oak Basal Area %, OBA%) may modulate soil microbial functioning. 28291612 1 5 theme OBA 225:227 arg1 % 228:228 OBA% 225:228 OBA% 225:228 This study investigated how oak abundance in pine stands (using relative Oak Basal Area %, OBA%) may modulate soil microbial functioning. 28291612 9 6 theme tree 2088:2091 arg1 species 2093:2099 tree species 2088:2099 tree species 2088:2099 Our study indeed revealed that, when evaluating the benefits of forest mixed stand on soil microbial functioning and OM turnover, the identity of tree species has to be considered. 28291612 7 7 theme ammonium 1528:1535 arg1 contents 1537:1544 ammonium contents 1528:1544 ammonium contents 1528:1544 Conversely, in A-horizon Q. pubescens and P. sylvestris stands, the relationship between OBA% and either cellulase activities, polysaccharides or ammonium contents, suggested a non-additive effect of Q. pubescens and P. sylvestris, enhancing mineralization of the OM labile fraction for plots characterized by an OBA% ranging from 40% to 60%. 28291612 6 8 theme OBA 1066:1068 arg1 % 1069:1069 OBA% 1066:1069 OBA% 1066:1069 Catabolic profiles of microbial communities from A-horizon were significantly modulated in Q. ilex and P. halepensis stand by OBA% and alkyl C to carboxyl C ratio (characteristic of cutin from Q. ilex tissues) and in Q. pubescens and P. sylvestris stands, by OBA% and pH. In A-horizon under Q. ilex and P. halepensis stands, linear regressions were found between catabolic diversity, microbial biomass and OBA% suggesting an additive effect. 28291612 4 9 theme catabolic 754:762 arg1 activities 711:720 enzyme activities 704:720 enzyme activities 704:720 Relations between OBA% and either soil chemical (C and N contents, quality of organic matter via solid-state NMR, pH, CaCO3) or microbial (enzyme activities, basal respiration, biomass and catabolic diversity via BIOLOG) characteristics were described. 28291612 4 9 theme catabolic 754:762 arg1 diversity 764:772 catabolic diversity 754:772 catabolic diversity 754:772 Relations between OBA% and either soil chemical (C and N contents, quality of organic matter via solid-state NMR, pH, CaCO3) or microbial (enzyme activities, basal respiration, biomass and catabolic diversity via BIOLOG) characteristics were described. 28291612 6 10 theme microbial 962:970 arg1 communities 972:982 microbial communities 962:982 microbial communities 962:982 Catabolic profiles of microbial communities from A-horizon were significantly modulated in Q. ilex and P. halepensis stand by OBA% and alkyl C to carboxyl C ratio (characteristic of cutin from Q. ilex tissues) and in Q. pubescens and P. sylvestris stands, by OBA% and pH. In A-horizon under Q. ilex and P. halepensis stands, linear regressions were found between catabolic diversity, microbial biomass and OBA% suggesting an additive effect. 28291612 4 11 dep characteristics 786:800 arg1 either 592:597 either 592:597 either 592:597 Relations between OBA% and either soil chemical (C and N contents, quality of organic matter via solid-state NMR, pH, CaCO3) or microbial (enzyme activities, basal respiration, biomass and catabolic diversity via BIOLOG) characteristics were described. 28291612 4 11 dep characteristics 786:800 arg1 microbial 693:701 microbial 693:701 microbial 693:701 Relations between OBA% and either soil chemical (C and N contents, quality of organic matter via solid-state NMR, pH, CaCO3) or microbial (enzyme activities, basal respiration, biomass and catabolic diversity via BIOLOG) characteristics were described. 28291612 5 12 from decrease 841:848 arg1 fraction 870:877 the recalcitrant fraction 853:877 the recalcitrant fraction of organic matter (OM) in OLF 853:907 OBA% increase led to a decrease in the recalcitrant fraction of organic matter (OM) in OLF and promoted microbial growth. 28291612 6 13 theme cutin 1122:1126 arg1 characteristic 1104:1117 characteristic 1104:1117 characteristic 1104:1117 Catabolic profiles of microbial communities from A-horizon were significantly modulated in Q. ilex and P. halepensis stand by OBA% and alkyl C to carboxyl C ratio (characteristic of cutin from Q. ilex tissues) and in Q. pubescens and P. sylvestris stands, by OBA% and pH. In A-horizon under Q. ilex and P. halepensis stands, linear regressions were found between catabolic diversity, microbial biomass and OBA% suggesting an additive effect. 28291612 3 14 theme stand 497:501 arg1 types 488:492 the two types 480:492 the two types of stand (n=60) 480:508 We used a series of plots with OBA% ranging from 0 to 100% in the two types of stand (n=60) and both OLF and A-horizon compartments were analysed. 28291612 0 15 from pine 49:52 arg1 effect 25:30 Additive or non-additive effect 0:30 Additive or non-additive effect of mixing oak in pine stands on soil properties 0:78 Additive or non-additive effect of mixing oak in pine stands on soil properties depends on the tree species in Mediterranean forests. 28291612 6 16 theme characteristic 1104:1117 arg1 ratio 1097:1101 carboxyl C ratio 1086:1101 carboxyl C ratio (characteristic of cutin from Q. ilex tissues) 1086:1148 Catabolic profiles of microbial communities from A-horizon were significantly modulated in Q. ilex and P. halepensis stand by OBA% and alkyl C to carboxyl C ratio (characteristic of cutin from Q. ilex tissues) and in Q. pubescens and P. sylvestris stands, by OBA% and pH. In A-horizon under Q. ilex and P. halepensis stands, linear regressions were found between catabolic diversity, microbial biomass and OBA% suggesting an additive effect. 28291612 6 17 theme OBA 1346:1348 arg1 % 1349:1349 OBA% 1346:1349 OBA% 1346:1349 Catabolic profiles of microbial communities from A-horizon were significantly modulated in Q. ilex and P. halepensis stand by OBA% and alkyl C to carboxyl C ratio (characteristic of cutin from Q. ilex tissues) and in Q. pubescens and P. sylvestris stands, by OBA% and pH. In A-horizon under Q. ilex and P. halepensis stands, linear regressions were found between catabolic diversity, microbial biomass and OBA% suggesting an additive effect. 28291612 7 18 theme cellulase 1487:1495 arg1 activities 1497:1506 OBA% and either cellulase activities 1471:1506 OBA% and either cellulase activities 1471:1506 Conversely, in A-horizon Q. pubescens and P. sylvestris stands, the relationship between OBA% and either cellulase activities, polysaccharides or ammonium contents, suggested a non-additive effect of Q. pubescens and P. sylvestris, enhancing mineralization of the OM labile fraction for plots characterized by an OBA% ranging from 40% to 60%. 28291612 4 19 theme chemical 604:611 arg1 soil 599:602 soil chemical 599:611 soil chemical (C and N contents, quality of organic matter via solid-state NMR, pH, CaCO3) 599:688 Relations between OBA% and either soil chemical (C and N contents, quality of organic matter via solid-state NMR, pH, CaCO3) or microbial (enzyme activities, basal respiration, biomass and catabolic diversity via BIOLOG) characteristics were described. 28291612 5 20 theme organic 882:888 arg1 OM 898:899 OM 898:899 OM 898:899 OBA% increase led to a decrease in the recalcitrant fraction of organic matter (OM) in OLF and promoted microbial growth. 28291612 5 20 theme organic 882:888 arg1 matter 890:895 organic matter 882:895 organic matter (OM) 882:900 OBA% increase led to a decrease in the recalcitrant fraction of organic matter (OM) in OLF and promoted microbial growth. 28291612 6 21 theme Q. 1031:1032 arg1 ilex 1034:1037 Q. ilex 1031:1037 Q. ilex 1031:1037 Catabolic profiles of microbial communities from A-horizon were significantly modulated in Q. ilex and P. halepensis stand by OBA% and alkyl C to carboxyl C ratio (characteristic of cutin from Q. ilex tissues) and in Q. pubescens and P. sylvestris stands, by OBA% and pH. In A-horizon under Q. ilex and P. halepensis stands, linear regressions were found between catabolic diversity, microbial biomass and OBA% suggesting an additive effect. 28291612 7 22 dep pubescens 1410:1418 arg1 stands 1438:1443 stands 1438:1443 stands 1438:1443 Conversely, in A-horizon Q. pubescens and P. sylvestris stands, the relationship between OBA% and either cellulase activities, polysaccharides or ammonium contents, suggested a non-additive effect of Q. pubescens and P. sylvestris, enhancing mineralization of the OM labile fraction for plots characterized by an OBA% ranging from 40% to 60%. 28291612 1 23 from abundance 166:174 arg1 pine 179:182 pine stands 179:189 pine stands (using relative Oak Basal Area %, OBA%) 179:229 This study investigated how oak abundance in pine stands (using relative Oak Basal Area %, OBA%) may modulate soil microbial functioning. 28291612 0 24 theme non-additive 12:23 arg1 effect 25:30 Additive or non-additive effect 0:30 Additive or non-additive effect of mixing oak in pine stands on soil properties 0:78 Additive or non-additive effect of mixing oak in pine stands on soil properties depends on the tree species in Mediterranean forests. 28291612 7 25 theme OBA 1471:1473 arg1 % 1474:1474 OBA% 1471:1474 OBA% 1471:1474 Conversely, in A-horizon Q. pubescens and P. sylvestris stands, the relationship between OBA% and either cellulase activities, polysaccharides or ammonium contents, suggested a non-additive effect of Q. pubescens and P. sylvestris, enhancing mineralization of the OM labile fraction for plots characterized by an OBA% ranging from 40% to 60%. 28291612 7 26 dep P. 1424:1425 arg1 sylvestris 1427:1436 P. sylvestris 1424:1436 P. sylvestris 1424:1436 Conversely, in A-horizon Q. pubescens and P. sylvestris stands, the relationship between OBA% and either cellulase activities, polysaccharides or ammonium contents, suggested a non-additive effect of Q. pubescens and P. sylvestris, enhancing mineralization of the OM labile fraction for plots characterized by an OBA% ranging from 40% to 60%. 28291612 9 27 theme mixed 2013:2017 arg1 stand 2019:2023 forest mixed stand 2006:2023 forest mixed stand 2006:2023 Our study indeed revealed that, when evaluating the benefits of forest mixed stand on soil microbial functioning and OM turnover, the identity of tree species has to be considered. 28291612 7 28 theme OBA 1695:1697 arg1 % 1698:1698 an OBA% 1692:1698 an OBA% ranging from 40% to 60% 1692:1722 Conversely, in A-horizon Q. pubescens and P. sylvestris stands, the relationship between OBA% and either cellulase activities, polysaccharides or ammonium contents, suggested a non-additive effect of Q. pubescens and P. sylvestris, enhancing mineralization of the OM labile fraction for plots characterized by an OBA% ranging from 40% to 60%. 28291612 0 29 from oak 42:44 arg1 pine 49:52 pine stands 49:59 pine stands 49:59 Additive or non-additive effect of mixing oak in pine stands on soil properties depends on the tree species in Mediterranean forests. 28291612 9 30 theme forest 2006:2011 arg1 stand 2019:2023 forest mixed stand 2006:2023 forest mixed stand 2006:2023 Our study indeed revealed that, when evaluating the benefits of forest mixed stand on soil microbial functioning and OM turnover, the identity of tree species has to be considered. 28291612 6 31 from A-horizon 989:997 arg1 profiles 950:957 Catabolic profiles 940:957 Catabolic profiles of microbial communities from A-horizon 940:997 Catabolic profiles of microbial communities from A-horizon were significantly modulated in Q. ilex and P. halepensis stand by OBA% and alkyl C to carboxyl C ratio (characteristic of cutin from Q. ilex tissues) and in Q. pubescens and P. sylvestris stands, by OBA% and pH. In A-horizon under Q. ilex and P. halepensis stands, linear regressions were found between catabolic diversity, microbial biomass and OBA% suggesting an additive effect. 28291612 2 32 theme Pinus 349:353 arg1 or 373:374 Pinus halepensis Miller or 349:374 Pinus halepensis Miller or of Q. pubescens mixed with P. sylvestris 349:415 Forests were composed of sclerophyllous species i.e. Quercus ilex mixed with Pinus halepensis Miller or of Q. pubescens mixed with P. sylvestris. 28291612 6 33 dep Q. 1157:1158 arg1 pubescens 1160:1168 Q. pubescens 1157:1168 Q. pubescens 1157:1168 Catabolic profiles of microbial communities from A-horizon were significantly modulated in Q. ilex and P. halepensis stand by OBA% and alkyl C to carboxyl C ratio (characteristic of cutin from Q. ilex tissues) and in Q. pubescens and P. sylvestris stands, by OBA% and pH. In A-horizon under Q. ilex and P. halepensis stands, linear regressions were found between catabolic diversity, microbial biomass and OBA% suggesting an additive effect. 28291612 6 33 dep Q. 1157:1158 arg1 stands 1188:1193 stands 1188:1193 stands 1188:1193 Catabolic profiles of microbial communities from A-horizon were significantly modulated in Q. ilex and P. halepensis stand by OBA% and alkyl C to carboxyl C ratio (characteristic of cutin from Q. ilex tissues) and in Q. pubescens and P. sylvestris stands, by OBA% and pH. In A-horizon under Q. ilex and P. halepensis stands, linear regressions were found between catabolic diversity, microbial biomass and OBA% suggesting an additive effect. 28291612 5 34 theme % 821:821 arg1 increase 823:830 OBA% increase 818:830 OBA% increase 818:830 OBA% increase led to a decrease in the recalcitrant fraction of organic matter (OM) in OLF and promoted microbial growth. 28291612 0 35 theme Additive 0:7 arg1 effect 25:30 Additive or non-additive effect 0:30 Additive or non-additive effect of mixing oak in pine stands on soil properties 0:78 Additive or non-additive effect of mixing oak in pine stands on soil properties depends on the tree species in Mediterranean forests. 28291612 6 36 theme additive 1365:1372 arg1 effect 1374:1379 an additive effect 1362:1379 an additive effect 1362:1379 Catabolic profiles of microbial communities from A-horizon were significantly modulated in Q. ilex and P. halepensis stand by OBA% and alkyl C to carboxyl C ratio (characteristic of cutin from Q. ilex tissues) and in Q. pubescens and P. sylvestris stands, by OBA% and pH. In A-horizon under Q. ilex and P. halepensis stands, linear regressions were found between catabolic diversity, microbial biomass and OBA% suggesting an additive effect. 28291612 4 37 dep soil 599:602 arg1 quality 632:638 quality 632:638 quality of organic matter via solid-state NMR 632:676 Relations between OBA% and either soil chemical (C and N contents, quality of organic matter via solid-state NMR, pH, CaCO3) or microbial (enzyme activities, basal respiration, biomass and catabolic diversity via BIOLOG) characteristics were described. 28291612 4 37 dep soil 599:602 arg1 C 614:614 C 614:614 C 614:614 Relations between OBA% and either soil chemical (C and N contents, quality of organic matter via solid-state NMR, pH, CaCO3) or microbial (enzyme activities, basal respiration, biomass and catabolic diversity via BIOLOG) characteristics were described. 28291612 4 37 dep soil 599:602 arg1 contents 622:629 N contents 620:629 N contents 620:629 Relations between OBA% and either soil chemical (C and N contents, quality of organic matter via solid-state NMR, pH, CaCO3) or microbial (enzyme activities, basal respiration, biomass and catabolic diversity via BIOLOG) characteristics were described. 28291612 2 38 theme pubescens 382:390 arg1 or 373:374 Pinus halepensis Miller or 349:374 Pinus halepensis Miller or of Q. pubescens mixed with P. sylvestris 349:415 Forests were composed of sclerophyllous species i.e. Quercus ilex mixed with Pinus halepensis Miller or of Q. pubescens mixed with P. sylvestris. 28291612 4 39 theme N 620:620 arg1 contents 622:629 N contents 620:629 N contents 620:629 Relations between OBA% and either soil chemical (C and N contents, quality of organic matter via solid-state NMR, pH, CaCO3) or microbial (enzyme activities, basal respiration, biomass and catabolic diversity via BIOLOG) characteristics were described. 28291612 6 40 theme OBA 1199:1201 arg1 % 1202:1202 OBA% 1199:1202 OBA% 1199:1202 Catabolic profiles of microbial communities from A-horizon were significantly modulated in Q. ilex and P. halepensis stand by OBA% and alkyl C to carboxyl C ratio (characteristic of cutin from Q. ilex tissues) and in Q. pubescens and P. sylvestris stands, by OBA% and pH. In A-horizon under Q. ilex and P. halepensis stands, linear regressions were found between catabolic diversity, microbial biomass and OBA% suggesting an additive effect. 28291612 7 41 theme fraction 1656:1663 arg1 mineralization 1624:1637 mineralization 1624:1637 mineralization of the OM labile fraction for plots characterized by an OBA% ranging from 40% to 60% 1624:1722 Conversely, in A-horizon Q. pubescens and P. sylvestris stands, the relationship between OBA% and either cellulase activities, polysaccharides or ammonium contents, suggested a non-additive effect of Q. pubescens and P. sylvestris, enhancing mineralization of the OM labile fraction for plots characterized by an OBA% ranging from 40% to 60%. 28291612 0 42 dep pine 49:52 arg1 stands 54:59 stands 54:59 stands 54:59 Additive or non-additive effect of mixing oak in pine stands on soil properties depends on the tree species in Mediterranean forests. 28291612 3 43 theme A-horizon 527:535 arg1 compartments 537:548 both OLF and A-horizon compartments 514:548 both OLF and A-horizon compartments 514:548 We used a series of plots with OBA% ranging from 0 to 100% in the two types of stand (n=60) and both OLF and A-horizon compartments were analysed. 28291612 2 44 theme Miller 366:371 arg1 or 373:374 Pinus halepensis Miller or 349:374 Pinus halepensis Miller or of Q. pubescens mixed with P. sylvestris 349:415 Forests were composed of sclerophyllous species i.e. Quercus ilex mixed with Pinus halepensis Miller or of Q. pubescens mixed with P. sylvestris. 28291612 8 45 theme favored 1751:1757 arg1 dynamics 1769:1776 pine thus favored microbial dynamics 1741:1776 pine thus favored microbial dynamics in both type of 1741:1792 Mixing oak with pine thus favored microbial dynamics in both type of stands though OBA% print varied with tree species and consequently sustainable soil functioning depend strongly on the composition of mixed stands. 28291612 7 46 theme OM 1646:1647 arg1 fraction 1656:1663 the OM labile fraction 1642:1663 the OM labile fraction 1642:1663 Conversely, in A-horizon Q. pubescens and P. sylvestris stands, the relationship between OBA% and either cellulase activities, polysaccharides or ammonium contents, suggested a non-additive effect of Q. pubescens and P. sylvestris, enhancing mineralization of the OM labile fraction for plots characterized by an OBA% ranging from 40% to 60%. 28291612 8 47 theme % 1811:1811 arg1 print 1813:1817 OBA% print 1808:1817 OBA% print 1808:1817 Mixing oak with pine thus favored microbial dynamics in both type of stands though OBA% print varied with tree species and consequently sustainable soil functioning depend strongly on the composition of mixed stands. 28291612 3 48 theme OLF 519:521 arg1 compartments 537:548 both OLF and A-horizon compartments 514:548 both OLF and A-horizon compartments 514:548 We used a series of plots with OBA% ranging from 0 to 100% in the two types of stand (n=60) and both OLF and A-horizon compartments were analysed. 28291612 0 49 theme oak 42:44 arg1 effect 25:30 Additive or non-additive effect 0:30 Additive or non-additive effect of mixing oak in pine stands on soil properties 0:78 Additive or non-additive effect of mixing oak in pine stands on soil properties depends on the tree species in Mediterranean forests. 28291612 1 50 theme functioning 259:269 arg1 soil 244:247 soil 244:247 soil microbial functioning 244:269 This study investigated how oak abundance in pine stands (using relative Oak Basal Area %, OBA%) may modulate soil microbial functioning. 28291612 5 51 theme recalcitrant 857:868 arg1 fraction 870:877 the recalcitrant fraction 853:877 the recalcitrant fraction of organic matter (OM) in OLF 853:907 OBA% increase led to a decrease in the recalcitrant fraction of organic matter (OM) in OLF and promoted microbial growth. 28291612 7 52 theme pubescens 1585:1593 arg1 effect 1572:1577 a non-additive effect 1557:1577 a non-additive effect of Q. pubescens and P. sylvestris 1557:1611 Conversely, in A-horizon Q. pubescens and P. sylvestris stands, the relationship between OBA% and either cellulase activities, polysaccharides or ammonium contents, suggested a non-additive effect of Q. pubescens and P. sylvestris, enhancing mineralization of the OM labile fraction for plots characterized by an OBA% ranging from 40% to 60%. 28291612 6 53 theme Catabolic 940:948 arg1 profiles 950:957 Catabolic profiles 940:957 Catabolic profiles of microbial communities from A-horizon 940:997 Catabolic profiles of microbial communities from A-horizon were significantly modulated in Q. ilex and P. halepensis stand by OBA% and alkyl C to carboxyl C ratio (characteristic of cutin from Q. ilex tissues) and in Q. pubescens and P. sylvestris stands, by OBA% and pH. In A-horizon under Q. ilex and P. halepensis stands, linear regressions were found between catabolic diversity, microbial biomass and OBA% suggesting an additive effect. 28291612 8 54 dep varied 1819:1824 arg1 functioning 1878:1888 functioning 1878:1888 varied with tree species and consequently sustainable soil functioning depend strongly on the composition of mixed stands 1819:1939 Mixing oak with pine thus favored microbial dynamics in both type of stands though OBA% print varied with tree species and consequently sustainable soil functioning depend strongly on the composition of mixed stands. 28291612 4 55 theme matter 651:656 arg1 quality 632:638 quality 632:638 quality of organic matter via solid-state NMR 632:676 Relations between OBA% and either soil chemical (C and N contents, quality of organic matter via solid-state NMR, pH, CaCO3) or microbial (enzyme activities, basal respiration, biomass and catabolic diversity via BIOLOG) characteristics were described. 28291612 4 55 theme matter 651:656 arg1 C 614:614 C 614:614 C 614:614 Relations between OBA% and either soil chemical (C and N contents, quality of organic matter via solid-state NMR, pH, CaCO3) or microbial (enzyme activities, basal respiration, biomass and catabolic diversity via BIOLOG) characteristics were described. 28291612 8 56 with oak 1732:1734 arg1 dynamics 1769:1776 pine thus favored microbial dynamics 1741:1776 pine thus favored microbial dynamics in both type of 1741:1792 Mixing oak with pine thus favored microbial dynamics in both type of stands though OBA% print varied with tree species and consequently sustainable soil functioning depend strongly on the composition of mixed stands. 28291612 9 57 theme microbial 2033:2041 arg1 soil 2028:2031 soil microbial functioning 2028:2053 soil microbial functioning 2028:2053 Our study indeed revealed that, when evaluating the benefits of forest mixed stand on soil microbial functioning and OM turnover, the identity of tree species has to be considered. 28291612 1 58 theme using 192:196 arg1 % 222:222 using relative Oak Basal Area % 192:222 using relative Oak Basal Area % 192:222 This study investigated how oak abundance in pine stands (using relative Oak Basal Area %, OBA%) may modulate soil microbial functioning. 28291612 1 58 theme using 192:196 arg1 % 228:228 OBA% 225:228 OBA% 225:228 This study investigated how oak abundance in pine stands (using relative Oak Basal Area %, OBA%) may modulate soil microbial functioning. 28291612 8 59 theme tree 1831:1834 arg1 species 1836:1842 tree species 1831:1842 tree species 1831:1842 Mixing oak with pine thus favored microbial dynamics in both type of stands though OBA% print varied with tree species and consequently sustainable soil functioning depend strongly on the composition of mixed stands. 28291612 9 60 theme stand 2019:2023 arg1 benefits 1994:2001 the benefits 1990:2001 the benefits of forest mixed stand on soil microbial functioning and OM turnover 1990:2069 Our study indeed revealed that, when evaluating the benefits of forest mixed stand on soil microbial functioning and OM turnover, the identity of tree species has to be considered. 28291612 4 61 theme solid-state 662:672 arg1 NMR 674:676 solid-state NMR 662:676 solid-state NMR 662:676 Relations between OBA% and either soil chemical (C and N contents, quality of organic matter via solid-state NMR, pH, CaCO3) or microbial (enzyme activities, basal respiration, biomass and catabolic diversity via BIOLOG) characteristics were described. 28291612 3 62 theme OBA 449:451 arg1 % 452:452 OBA% 449:452 OBA% ranging from 0 to 100% in the two types of stand (n=60) 449:508 We used a series of plots with OBA% ranging from 0 to 100% in the two types of stand (n=60) and both OLF and A-horizon compartments were analysed. 28291612 1 63 theme Oak 207:209 arg1 % 222:222 using relative Oak Basal Area % 192:222 using relative Oak Basal Area % 192:222 This study investigated how oak abundance in pine stands (using relative Oak Basal Area %, OBA%) may modulate soil microbial functioning. 28291612 1 63 theme Oak 207:209 arg1 % 228:228 OBA% 225:228 OBA% 225:228 This study investigated how oak abundance in pine stands (using relative Oak Basal Area %, OBA%) may modulate soil microbial functioning. 28291612 7 64 theme non-additive 1559:1570 arg1 effect 1572:1577 a non-additive effect 1557:1577 a non-additive effect of Q. pubescens and P. sylvestris 1557:1611 Conversely, in A-horizon Q. pubescens and P. sylvestris stands, the relationship between OBA% and either cellulase activities, polysaccharides or ammonium contents, suggested a non-additive effect of Q. pubescens and P. sylvestris, enhancing mineralization of the OM labile fraction for plots characterized by an OBA% ranging from 40% to 60%. 28291612 5 65 from fraction 870:877 arg1 OLF 905:907 OLF 905:907 OLF 905:907 OBA% increase led to a decrease in the recalcitrant fraction of organic matter (OM) in OLF and promoted microbial growth. 28291612 3 66 with plots 438:442 arg1 % 452:452 OBA% 449:452 OBA% ranging from 0 to 100% in the two types of stand (n=60) 449:508 We used a series of plots with OBA% ranging from 0 to 100% in the two types of stand (n=60) and both OLF and A-horizon compartments were analysed. 28291612 3 67 theme plots 438:442 arg1 series 428:433 a series 426:433 a series of plots with OBA% ranging from 0 to 100% in the two types of stand (n=60) 426:508 We used a series of plots with OBA% ranging from 0 to 100% in the two types of stand (n=60) and both OLF and A-horizon compartments were analysed. 28291612 1 68 theme Area 217:220 arg1 % 222:222 using relative Oak Basal Area % 192:222 using relative Oak Basal Area % 192:222 This study investigated how oak abundance in pine stands (using relative Oak Basal Area %, OBA%) may modulate soil microbial functioning. 28291612 1 68 theme Area 217:220 arg1 % 228:228 OBA% 225:228 OBA% 225:228 This study investigated how oak abundance in pine stands (using relative Oak Basal Area %, OBA%) may modulate soil microbial functioning. 28291612 8 69 theme sustainable 1861:1871 arg1 soil 1873:1876 consequently sustainable soil 1848:1876 consequently sustainable soil 1848:1876 Mixing oak with pine thus favored microbial dynamics in both type of stands though OBA% print varied with tree species and consequently sustainable soil functioning depend strongly on the composition of mixed stands. 28291612 6 70 theme In 1212:1213 arg1 A-horizon 1215:1223 pH. In A-horizon 1208:1223 pH. In A-horizon under Q. ilex 1208:1237 Catabolic profiles of microbial communities from A-horizon were significantly modulated in Q. ilex and P. halepensis stand by OBA% and alkyl C to carboxyl C ratio (characteristic of cutin from Q. ilex tissues) and in Q. pubescens and P. sylvestris stands, by OBA% and pH. In A-horizon under Q. ilex and P. halepensis stands, linear regressions were found between catabolic diversity, microbial biomass and OBA% suggesting an additive effect. 28291612 6 71 theme alkyl 1075:1079 arg1 C 1081:1081 alkyl C 1075:1081 alkyl C 1075:1081 Catabolic profiles of microbial communities from A-horizon were significantly modulated in Q. ilex and P. halepensis stand by OBA% and alkyl C to carboxyl C ratio (characteristic of cutin from Q. ilex tissues) and in Q. pubescens and P. sylvestris stands, by OBA% and pH. In A-horizon under Q. ilex and P. halepensis stands, linear regressions were found between catabolic diversity, microbial biomass and OBA% suggesting an additive effect. 28291612 9 72 theme species 2093:2099 arg1 identity 2076:2083 the identity 2072:2083 the identity of tree species 2072:2099 Our study indeed revealed that, when evaluating the benefits of forest mixed stand on soil microbial functioning and OM turnover, the identity of tree species has to be considered. 28291612 1 73 theme oak 162:164 arg1 abundance 166:174 oak abundance 162:174 oak abundance in pine stands (using relative Oak Basal Area %, OBA%) 162:229 This study investigated how oak abundance in pine stands (using relative Oak Basal Area %, OBA%) may modulate soil microbial functioning. 28291612 6 74 theme communities 972:982 arg1 profiles 950:957 Catabolic profiles 940:957 Catabolic profiles of microbial communities from A-horizon 940:997 Catabolic profiles of microbial communities from A-horizon were significantly modulated in Q. ilex and P. halepensis stand by OBA% and alkyl C to carboxyl C ratio (characteristic of cutin from Q. ilex tissues) and in Q. pubescens and P. sylvestris stands, by OBA% and pH. In A-horizon under Q. ilex and P. halepensis stands, linear regressions were found between catabolic diversity, microbial biomass and OBA% suggesting an additive effect. 28291612 6 75 theme ilex 1136:1139 arg1 tissues 1141:1147 Q. ilex tissues 1133:1147 Q. ilex tissues 1133:1147 Catabolic profiles of microbial communities from A-horizon were significantly modulated in Q. ilex and P. halepensis stand by OBA% and alkyl C to carboxyl C ratio (characteristic of cutin from Q. ilex tissues) and in Q. pubescens and P. sylvestris stands, by OBA% and pH. In A-horizon under Q. ilex and P. halepensis stands, linear regressions were found between catabolic diversity, microbial biomass and OBA% suggesting an additive effect. 28291612 6 76 theme linear 1265:1270 arg1 regressions 1272:1282 linear regressions 1265:1282 linear regressions 1265:1282 Catabolic profiles of microbial communities from A-horizon were significantly modulated in Q. ilex and P. halepensis stand by OBA% and alkyl C to carboxyl C ratio (characteristic of cutin from Q. ilex tissues) and in Q. pubescens and P. sylvestris stands, by OBA% and pH. In A-horizon under Q. ilex and P. halepensis stands, linear regressions were found between catabolic diversity, microbial biomass and OBA% suggesting an additive effect. 28291612 9 77 from benefits 1994:2001 arg1 turnover 2062:2069 OM turnover 2059:2069 OM turnover 2059:2069 Our study indeed revealed that, when evaluating the benefits of forest mixed stand on soil microbial functioning and OM turnover, the identity of tree species has to be considered. 28291612 9 77 from benefits 1994:2001 arg1 soil 2028:2031 soil microbial functioning 2028:2053 soil microbial functioning 2028:2053 Our study indeed revealed that, when evaluating the benefits of forest mixed stand on soil microbial functioning and OM turnover, the identity of tree species has to be considered. 28291612 0 78 theme Mediterranean 111:123 arg1 forests 125:131 Mediterranean forests 111:131 Mediterranean forests 111:131 Additive or non-additive effect of mixing oak in pine stands on soil properties depends on the tree species in Mediterranean forests. 28291612 4 79 theme basal 723:727 arg1 activities 711:720 enzyme activities 704:720 enzyme activities 704:720 Relations between OBA% and either soil chemical (C and N contents, quality of organic matter via solid-state NMR, pH, CaCO3) or microbial (enzyme activities, basal respiration, biomass and catabolic diversity via BIOLOG) characteristics were described. 28291612 4 79 theme basal 723:727 arg1 respiration 729:739 basal respiration 723:739 basal respiration 723:739 Relations between OBA% and either soil chemical (C and N contents, quality of organic matter via solid-state NMR, pH, CaCO3) or microbial (enzyme activities, basal respiration, biomass and catabolic diversity via BIOLOG) characteristics were described. 28291612 6 80 theme P. 1043:1044 arg1 stand 1057:1061 P. halepensis stand 1043:1061 P. halepensis stand 1043:1061 Catabolic profiles of microbial communities from A-horizon were significantly modulated in Q. ilex and P. halepensis stand by OBA% and alkyl C to carboxyl C ratio (characteristic of cutin from Q. ilex tissues) and in Q. pubescens and P. sylvestris stands, by OBA% and pH. In A-horizon under Q. ilex and P. halepensis stands, linear regressions were found between catabolic diversity, microbial biomass and OBA% suggesting an additive effect. 28291612 4 81 dep C 614:614 arg1 CaCO3 683:687 CaCO3 683:687 CaCO3 683:687 Relations between OBA% and either soil chemical (C and N contents, quality of organic matter via solid-state NMR, pH, CaCO3) or microbial (enzyme activities, basal respiration, biomass and catabolic diversity via BIOLOG) characteristics were described. 28291612 4 81 dep C 614:614 arg1 pH 679:680 pH 679:680 pH 679:680 Relations between OBA% and either soil chemical (C and N contents, quality of organic matter via solid-state NMR, pH, CaCO3) or microbial (enzyme activities, basal respiration, biomass and catabolic diversity via BIOLOG) characteristics were described. 28291612 8 82 theme mixed 1928:1932 arg1 composition 1913:1923 the composition 1909:1923 the composition of mixed stands 1909:1939 Mixing oak with pine thus favored microbial dynamics in both type of stands though OBA% print varied with tree species and consequently sustainable soil functioning depend strongly on the composition of mixed stands. 28291612 5 83 theme matter 890:895 arg1 fraction 870:877 the recalcitrant fraction 853:877 the recalcitrant fraction of organic matter (OM) in OLF 853:907 OBA% increase led to a decrease in the recalcitrant fraction of organic matter (OM) in OLF and promoted microbial growth. 28291612 6 84 theme microbial 1324:1332 arg1 biomass 1334:1340 microbial biomass 1324:1340 microbial biomass 1324:1340 Catabolic profiles of microbial communities from A-horizon were significantly modulated in Q. ilex and P. halepensis stand by OBA% and alkyl C to carboxyl C ratio (characteristic of cutin from Q. ilex tissues) and in Q. pubescens and P. sylvestris stands, by OBA% and pH. In A-horizon under Q. ilex and P. halepensis stands, linear regressions were found between catabolic diversity, microbial biomass and OBA% suggesting an additive effect. 28291612 3 85 dep 100 472:474 arg1 to 469:470 to 469:470 to 469:470 We used a series of plots with OBA% ranging from 0 to 100% in the two types of stand (n=60) and both OLF and A-horizon compartments were analysed. 28291612 8 86 theme pine 1741:1744 arg1 dynamics 1769:1776 pine thus favored microbial dynamics 1741:1776 pine thus favored microbial dynamics in both type of 1741:1792 Mixing oak with pine thus favored microbial dynamics in both type of stands though OBA% print varied with tree species and consequently sustainable soil functioning depend strongly on the composition of mixed stands. 28291612 0 87 from effect 25:30 arg1 pine 49:52 pine stands 49:59 pine stands 49:59 Additive or non-additive effect of mixing oak in pine stands on soil properties depends on the tree species in Mediterranean forests. 28291612 0 87 from effect 25:30 arg1 properties 69:78 soil properties 64:78 soil properties 64:78 Additive or non-additive effect of mixing oak in pine stands on soil properties depends on the tree species in Mediterranean forests. 28291612 6 88 dep P. 1043:1044 arg1 halepensis 1046:1055 halepensis 1046:1055 halepensis 1046:1055 Catabolic profiles of microbial communities from A-horizon were significantly modulated in Q. ilex and P. halepensis stand by OBA% and alkyl C to carboxyl C ratio (characteristic of cutin from Q. ilex tissues) and in Q. pubescens and P. sylvestris stands, by OBA% and pH. In A-horizon under Q. ilex and P. halepensis stands, linear regressions were found between catabolic diversity, microbial biomass and OBA% suggesting an additive effect. 28291612 0 89 theme soil 64:67 arg1 properties 69:78 soil properties 64:78 soil properties 64:78 Additive or non-additive effect of mixing oak in pine stands on soil properties depends on the tree species in Mediterranean forests. 28291612 7 90 theme % 1474:1474 arg1 activities 1497:1506 OBA% and either cellulase activities 1471:1506 OBA% and either cellulase activities 1471:1506 Conversely, in A-horizon Q. pubescens and P. sylvestris stands, the relationship between OBA% and either cellulase activities, polysaccharides or ammonium contents, suggested a non-additive effect of Q. pubescens and P. sylvestris, enhancing mineralization of the OM labile fraction for plots characterized by an OBA% ranging from 40% to 60%. 28291612 6 91 theme Q. 1133:1134 arg1 tissues 1141:1147 Q. ilex tissues 1133:1147 Q. ilex tissues 1133:1147 Catabolic profiles of microbial communities from A-horizon were significantly modulated in Q. ilex and P. halepensis stand by OBA% and alkyl C to carboxyl C ratio (characteristic of cutin from Q. ilex tissues) and in Q. pubescens and P. sylvestris stands, by OBA% and pH. In A-horizon under Q. ilex and P. halepensis stands, linear regressions were found between catabolic diversity, microbial biomass and OBA% suggesting an additive effect. 28291612 4 92 theme OBA 583:585 arg1 % 586:586 OBA% 583:586 OBA% 583:586 Relations between OBA% and either soil chemical (C and N contents, quality of organic matter via solid-state NMR, pH, CaCO3) or microbial (enzyme activities, basal respiration, biomass and catabolic diversity via BIOLOG) characteristics were described. 28291612 2 93 dep ilex 333:336 arg1 i.e. 320:323 i.e. 320:323 i.e. 320:323 Forests were composed of sclerophyllous species i.e. Quercus ilex mixed with Pinus halepensis Miller or of Q. pubescens mixed with P. sylvestris. 28291612 1 94 dep functioning 259:269 arg1 microbial 249:257 microbial 249:257 microbial 249:257 This study investigated how oak abundance in pine stands (using relative Oak Basal Area %, OBA%) may modulate soil microbial functioning. 28291612 9 95 theme functioning 2043:2053 arg1 soil 2028:2031 soil microbial functioning 2028:2053 soil microbial functioning 2028:2053 Our study indeed revealed that, when evaluating the benefits of forest mixed stand on soil microbial functioning and OM turnover, the identity of tree species has to be considered. 28291612 8 96 theme Mixing 1725:1730 arg1 oak 1732:1734 Mixing oak 1725:1734 Mixing oak with pine thus favored microbial dynamics in both type of 1725:1792 Mixing oak with pine thus favored microbial dynamics in both type of stands though OBA% print varied with tree species and consequently sustainable soil functioning depend strongly on the composition of mixed stands. 28291612 6 97 from tissues 1141:1147 arg1 cutin 1122:1126 cutin 1122:1126 cutin from Q. ilex tissues 1122:1147 Catabolic profiles of microbial communities from A-horizon were significantly modulated in Q. ilex and P. halepensis stand by OBA% and alkyl C to carboxyl C ratio (characteristic of cutin from Q. ilex tissues) and in Q. pubescens and P. sylvestris stands, by OBA% and pH. In A-horizon under Q. ilex and P. halepensis stands, linear regressions were found between catabolic diversity, microbial biomass and OBA% suggesting an additive effect. 28291612 5 98 theme OBA 818:820 arg1 increase 823:830 OBA% increase 818:830 OBA% increase 818:830 OBA% increase led to a decrease in the recalcitrant fraction of organic matter (OM) in OLF and promoted microbial growth. 28291612 6 99 theme pH. 1208:1210 arg1 A-horizon 1215:1223 pH. In A-horizon 1208:1223 pH. In A-horizon under Q. ilex 1208:1237 Catabolic profiles of microbial communities from A-horizon were significantly modulated in Q. ilex and P. halepensis stand by OBA% and alkyl C to carboxyl C ratio (characteristic of cutin from Q. ilex tissues) and in Q. pubescens and P. sylvestris stands, by OBA% and pH. In A-horizon under Q. ilex and P. halepensis stands, linear regressions were found between catabolic diversity, microbial biomass and OBA% suggesting an additive effect. 28291612 5 100 theme microbial 922:930 arg1 growth 932:937 microbial growth 922:937 microbial growth 922:937 OBA% increase led to a decrease in the recalcitrant fraction of organic matter (OM) in OLF and promoted microbial growth. 28291612 6 101 dep P. 1174:1175 arg1 sylvestris 1177:1186 P. sylvestris 1174:1186 P. sylvestris 1174:1186 Catabolic profiles of microbial communities from A-horizon were significantly modulated in Q. ilex and P. halepensis stand by OBA% and alkyl C to carboxyl C ratio (characteristic of cutin from Q. ilex tissues) and in Q. pubescens and P. sylvestris stands, by OBA% and pH. In A-horizon under Q. ilex and P. halepensis stands, linear regressions were found between catabolic diversity, microbial biomass and OBA% suggesting an additive effect. 28291612 8 102 from dynamics 1769:1776 arg1 type 1786:1789 both type 1781:1789 both type of 1781:1792 Mixing oak with pine thus favored microbial dynamics in both type of stands though OBA% print varied with tree species and consequently sustainable soil functioning depend strongly on the composition of mixed stands. 28291612 7 103 theme labile 1649:1654 arg1 fraction 1656:1663 the OM labile fraction 1642:1663 the OM labile fraction 1642:1663 Conversely, in A-horizon Q. pubescens and P. sylvestris stands, the relationship between OBA% and either cellulase activities, polysaccharides or ammonium contents, suggested a non-additive effect of Q. pubescens and P. sylvestris, enhancing mineralization of the OM labile fraction for plots characterized by an OBA% ranging from 40% to 60%. 28291612 4 104 dep either 592:597 arg1 soil 599:602 soil chemical 599:611 soil chemical (C and N contents, quality of organic matter via solid-state NMR, pH, CaCO3) 599:688 Relations between OBA% and either soil chemical (C and N contents, quality of organic matter via solid-state NMR, pH, CaCO3) or microbial (enzyme activities, basal respiration, biomass and catabolic diversity via BIOLOG) characteristics were described. 28291612 8 105 theme OBA 1808:1810 arg1 print 1813:1817 OBA% print 1808:1817 OBA% print 1808:1817 Mixing oak with pine thus favored microbial dynamics in both type of stands though OBA% print varied with tree species and consequently sustainable soil functioning depend strongly on the composition of mixed stands. 28291612 2 106 theme Q. 379:380 arg1 pubescens 382:390 Q. pubescens 379:390 Q. pubescens mixed with P. sylvestris 379:415 Forests were composed of sclerophyllous species i.e. Quercus ilex mixed with Pinus halepensis Miller or of Q. pubescens mixed with P. sylvestris. 28291612 2 107 theme Quercus 325:331 arg1 ilex 333:336 Quercus ilex 325:336 Quercus ilex mixed with Pinus halepensis Miller or of Q. pubescens mixed with P. sylvestris 325:415 Forests were composed of sclerophyllous species i.e. Quercus ilex mixed with Pinus halepensis Miller or of Q. pubescens mixed with P. sylvestris. 28291612 0 108 theme mixing 35:40 arg1 oak 42:44 mixing oak 35:44 mixing oak in pine stands 35:59 Additive or non-additive effect of mixing oak in pine stands on soil properties depends on the tree species in Mediterranean forests. 28291612 8 109 dep mixed 1928:1932 arg1 stands 1934:1939 stands 1934:1939 stands 1934:1939 Mixing oak with pine thus favored microbial dynamics in both type of stands though OBA% print varied with tree species and consequently sustainable soil functioning depend strongly on the composition of mixed stands. 28291612 3 110 used used 421:424 arg2 We 418:419 We 418:419 We 418:419 We used a series of plots with OBA% ranging from 0 to 100% in the two types of stand (n=60) and both OLF and A-horizon compartments were analysed. 28291612 2 111 theme halepensis 355:364 arg1 or 373:374 Pinus halepensis Miller or 349:374 Pinus halepensis Miller or of Q. pubescens mixed with P. sylvestris 349:415 Forests were composed of sclerophyllous species i.e. Quercus ilex mixed with Pinus halepensis Miller or of Q. pubescens mixed with P. sylvestris. 28291612 8 112 theme microbial 1759:1767 arg1 dynamics 1769:1776 pine thus favored microbial dynamics 1741:1776 pine thus favored microbial dynamics in both type of 1741:1792 Mixing oak with pine thus favored microbial dynamics in both type of stands though OBA% print varied with tree species and consequently sustainable soil functioning depend strongly on the composition of mixed stands. 28291612 7 113 theme sylvestris 1602:1611 arg1 effect 1572:1577 a non-additive effect 1557:1577 a non-additive effect of Q. pubescens and P. sylvestris 1557:1611 Conversely, in A-horizon Q. pubescens and P. sylvestris stands, the relationship between OBA% and either cellulase activities, polysaccharides or ammonium contents, suggested a non-additive effect of Q. pubescens and P. sylvestris, enhancing mineralization of the OM labile fraction for plots characterized by an OBA% ranging from 40% to 60%. 28291612 4 114 theme organic 643:649 arg1 matter 651:656 organic matter 643:656 organic matter 643:656 Relations between OBA% and either soil chemical (C and N contents, quality of organic matter via solid-state NMR, pH, CaCO3) or microbial (enzyme activities, basal respiration, biomass and catabolic diversity via BIOLOG) characteristics were described. 28291612 9 115 theme OM 2059:2060 arg1 turnover 2062:2069 OM turnover 2059:2069 OM turnover 2059:2069 Our study indeed revealed that, when evaluating the benefits of forest mixed stand on soil microbial functioning and OM turnover, the identity of tree species has to be considered. 28291612 1 116 theme relative 198:205 arg1 % 222:222 using relative Oak Basal Area % 192:222 using relative Oak Basal Area % 192:222 This study investigated how oak abundance in pine stands (using relative Oak Basal Area %, OBA%) may modulate soil microbial functioning. 28291612 1 116 theme relative 198:205 arg1 % 228:228 OBA% 225:228 OBA% 225:228 This study investigated how oak abundance in pine stands (using relative Oak Basal Area %, OBA%) may modulate soil microbial functioning. 28291612 7 117 theme Q. 1582:1583 arg1 pubescens 1585:1593 Q. pubescens 1582:1593 Q. pubescens 1582:1593 Conversely, in A-horizon Q. pubescens and P. sylvestris stands, the relationship between OBA% and either cellulase activities, polysaccharides or ammonium contents, suggested a non-additive effect of Q. pubescens and P. sylvestris, enhancing mineralization of the OM labile fraction for plots characterized by an OBA% ranging from 40% to 60%. 28291612 0 118 theme tree 95:98 arg1 species 100:106 the tree species 91:106 the tree species in Mediterranean forests 91:131 Additive or non-additive effect of mixing oak in pine stands on soil properties depends on the tree species in Mediterranean forests. 28291612 0 119 from species 100:106 arg1 forests 125:131 Mediterranean forests 111:131 Mediterranean forests 111:131 Additive or non-additive effect of mixing oak in pine stands on soil properties depends on the tree species in Mediterranean forests. 28291612 1 120 dep pine 179:182 arg1 % 222:222 using relative Oak Basal Area % 192:222 using relative Oak Basal Area % 192:222 This study investigated how oak abundance in pine stands (using relative Oak Basal Area %, OBA%) may modulate soil microbial functioning. 28291612 1 120 dep pine 179:182 arg1 % 228:228 OBA% 225:228 OBA% 225:228 This study investigated how oak abundance in pine stands (using relative Oak Basal Area %, OBA%) may modulate soil microbial functioning. 28291612 1 120 dep pine 179:182 arg1 stands 184:189 stands 184:189 stands 184:189 This study investigated how oak abundance in pine stands (using relative Oak Basal Area %, OBA%) may modulate soil microbial functioning. 28291612 4 121 dep microbial 693:701 arg1 diversity 764:772 catabolic diversity 754:772 catabolic diversity 754:772 Relations between OBA% and either soil chemical (C and N contents, quality of organic matter via solid-state NMR, pH, CaCO3) or microbial (enzyme activities, basal respiration, biomass and catabolic diversity via BIOLOG) characteristics were described. 28291612 4 121 dep microbial 693:701 arg1 biomass 742:748 biomass 742:748 biomass 742:748 Relations between OBA% and either soil chemical (C and N contents, quality of organic matter via solid-state NMR, pH, CaCO3) or microbial (enzyme activities, basal respiration, biomass and catabolic diversity via BIOLOG) characteristics were described. 28291612 4 121 dep microbial 693:701 arg1 activities 711:720 enzyme activities 704:720 enzyme activities 704:720 Relations between OBA% and either soil chemical (C and N contents, quality of organic matter via solid-state NMR, pH, CaCO3) or microbial (enzyme activities, basal respiration, biomass and catabolic diversity via BIOLOG) characteristics were described. 28291612 4 121 dep microbial 693:701 arg1 respiration 729:739 basal respiration 723:739 basal respiration 723:739 Relations between OBA% and either soil chemical (C and N contents, quality of organic matter via solid-state NMR, pH, CaCO3) or microbial (enzyme activities, basal respiration, biomass and catabolic diversity via BIOLOG) characteristics were described. 28291612 6 122 theme Q. 1231:1232 arg1 ilex 1234:1237 Q. ilex 1231:1237 Q. ilex 1231:1237 Catabolic profiles of microbial communities from A-horizon were significantly modulated in Q. ilex and P. halepensis stand by OBA% and alkyl C to carboxyl C ratio (characteristic of cutin from Q. ilex tissues) and in Q. pubescens and P. sylvestris stands, by OBA% and pH. In A-horizon under Q. ilex and P. halepensis stands, linear regressions were found between catabolic diversity, microbial biomass and OBA% suggesting an additive effect. 28291612 1 123 theme Basal 211:215 arg1 % 222:222 using relative Oak Basal Area % 192:222 using relative Oak Basal Area % 192:222 This study investigated how oak abundance in pine stands (using relative Oak Basal Area %, OBA%) may modulate soil microbial functioning. 28291612 1 123 theme Basal 211:215 arg1 % 228:228 OBA% 225:228 OBA% 225:228 This study investigated how oak abundance in pine stands (using relative Oak Basal Area %, OBA%) may modulate soil microbial functioning. 27974092 4 0 theme 5-100 g 617:623 arg1 l-1 625:627 5-100 g l-1 617:627 5-100 g l-1 617:627 Strain MRo-4T grew at 25-50 °C, at pH 7.0-8.8 and at an NaCl concentration of 5-100 g l-1. 27974092 8 1 theme DNA 975:977 arg1 content 960:966 The G+C content 952:966 The G+C content of the DNA 952:977 The G+C content of the DNA was 32.9 mol%. 27974092 8 1 theme DNA 975:977 arg1 % 991:991 32.9 mol% 983:991 32.9 mol% 983:991 The G+C content of the DNA was 32.9 mol%. 27974092 11 2 dep temperature 1378:1388 arg1 ranges 1407:1412 ranges 1407:1412 ranges 1407:1412 However, strains MRo-4T and S. faouarense SOL3f37T differed in temperature, pH and salinity ranges for growth, requirement for yeast extract and substrate profiles. 27974092 9 3 theme gene 1028:1031 arg1 sequences 1033:1041 16S rRNA gene sequences 1019:1041 16S rRNA gene sequences of strain MRo-4T and its nearest relatives 1019:1084 Phylogenetic analysis of 16S rRNA gene sequences of strain MRo-4T and its nearest relatives showed its affiliation to the genus Sporosalibacterium. 27974092 3 4 theme motile 468:473 arg1 rods 490:493 motile, spore-forming rods 468:493 motile, spore-forming rods 468:493 Cells of the novel isolate stained Gram-positive and were motile, spore-forming rods, 0.2-0.3 µm in width and 5-20 µm in length. 27974092 3 5 from 0.2-0.3 µm 496:505 arg1 5-20 µm 520:526 5-20 µm 520:526 5-20 µm 520:526 Cells of the novel isolate stained Gram-positive and were motile, spore-forming rods, 0.2-0.3 µm in width and 5-20 µm in length. 27974092 3 5 from 0.2-0.3 µm 496:505 arg1 width 510:514 width 510:514 width 510:514 Cells of the novel isolate stained Gram-positive and were motile, spore-forming rods, 0.2-0.3 µm in width and 5-20 µm in length. 27974092 12 6 theme novel 1579:1583 arg1 species 1585:1591 a novel species 1577:1591 a novel species 1577:1591 Based on the phylogenetic analysis and physiological properties of the novel isolate, we propose a novel species, Sporosalibacterium tautonense sp. 27974092 10 7 theme sequence 1293:1300 arg1 similarity 1302:1311 96.8 % 16S rRNA gene sequence similarity 1272:1311 96.8 % 16S rRNA gene sequence similarity 1272:1311 Sporosalibacteriumfaouarense SOL3f37T, the only valid published representative of the genus, appeared to be its closest relative (96.8 % 16S rRNA gene sequence similarity). 27974092 10 7 theme sequence 1293:1300 arg1 relative 1262:1269 its closest relative 1250:1269 its closest relative (96.8 % 16S rRNA gene sequence similarity) 1250:1312 Sporosalibacteriumfaouarense SOL3f37T, the only valid published representative of the genus, appeared to be its closest relative (96.8 % 16S rRNA gene sequence similarity). 27974092 7 8 theme major 867:871 arg1 iso-C15  890:897 iso-C15  890:897 iso-C15  890:897 The major fatty acids were iso-C15 : 0, iso-C15 : 0 dimethyl acetyl and anteiso-C15 : 0. 27974092 7 8 theme major 867:871 arg1 acids 879:883 The major fatty acids 863:883 The major fatty acids 863:883 The major fatty acids were iso-C15 : 0, iso-C15 : 0 dimethyl acetyl and anteiso-C15 : 0. 27974092 3 9 theme 0.2-0.3 µm 496:505 arg1 rods 490:493 motile, spore-forming rods 468:493 motile, spore-forming rods 468:493 Cells of the novel isolate stained Gram-positive and were motile, spore-forming rods, 0.2-0.3 µm in width and 5-20 µm in length. 27974092 9 10 theme rRNA 1023:1026 arg1 sequences 1033:1041 16S rRNA gene sequences 1019:1041 16S rRNA gene sequences of strain MRo-4T and its nearest relatives 1019:1084 Phylogenetic analysis of 16S rRNA gene sequences of strain MRo-4T and its nearest relatives showed its affiliation to the genus Sporosalibacterium. 27974092 10 11 theme gene 1288:1291 arg1 similarity 1302:1311 96.8 % 16S rRNA gene sequence similarity 1272:1311 96.8 % 16S rRNA gene sequence similarity 1272:1311 Sporosalibacteriumfaouarense SOL3f37T, the only valid published representative of the genus, appeared to be its closest relative (96.8 % 16S rRNA gene sequence similarity). 27974092 10 11 theme gene 1288:1291 arg1 relative 1262:1269 its closest relative 1250:1269 its closest relative (96.8 % 16S rRNA gene sequence similarity) 1250:1312 Sporosalibacteriumfaouarense SOL3f37T, the only valid published representative of the genus, appeared to be its closest relative (96.8 % 16S rRNA gene sequence similarity). 27974092 10 12 theme closest 1254:1260 arg1 relative 1262:1269 its closest relative 1250:1269 its closest relative (96.8 % 16S rRNA gene sequence similarity) 1250:1312 Sporosalibacteriumfaouarense SOL3f37T, the only valid published representative of the genus, appeared to be its closest relative (96.8 % 16S rRNA gene sequence similarity). 27974092 10 12 theme closest 1254:1260 arg1 similarity 1302:1311 96.8 % 16S rRNA gene sequence similarity 1272:1311 96.8 % 16S rRNA gene sequence similarity 1272:1311 Sporosalibacteriumfaouarense SOL3f37T, the only valid published representative of the genus, appeared to be its closest relative (96.8 % 16S rRNA gene sequence similarity). 27974092 11 13 theme substrate 1460:1468 arg1 profiles 1470:1477 substrate profiles 1460:1477 substrate profiles 1460:1477 However, strains MRo-4T and S. faouarense SOL3f37T differed in temperature, pH and salinity ranges for growth, requirement for yeast extract and substrate profiles. 27974092 11 14 theme growth 1418:1423 arg1 requirement 1426:1436 growth, requirement 1418:1436 requirement 1426:1436 However, strains MRo-4T and S. faouarense SOL3f37T differed in temperature, pH and salinity ranges for growth, requirement for yeast extract and substrate profiles. 27974092 5 15 theme yeast 662:666 arg1 peptone 677:683 peptone 677:683 peptone 677:683 The isolate was able to ferment yeast extract, peptone and mono-, oligo- and polysaccharides, including cellulose and chitin. 27974092 5 15 theme yeast 662:666 arg1 extract 668:674 yeast extract 662:674 yeast extract 662:674 The isolate was able to ferment yeast extract, peptone and mono-, oligo- and polysaccharides, including cellulose and chitin. 27974092 5 15 theme yeast 662:666 arg1 oligo- 696:701 oligo- 696:701 oligo- 696:701 The isolate was able to ferment yeast extract, peptone and mono-, oligo- and polysaccharides, including cellulose and chitin. 27974092 5 15 theme yeast 662:666 arg1 polysaccharides 707:721 polysaccharides 707:721 polysaccharides 707:721 The isolate was able to ferment yeast extract, peptone and mono-, oligo- and polysaccharides, including cellulose and chitin. 27974092 5 15 theme yeast 662:666 arg1 mono- 689:693 mono- 689:693 mono- 689:693 The isolate was able to ferment yeast extract, peptone and mono-, oligo- and polysaccharides, including cellulose and chitin. 27974092 2 16 theme mat 324:326 arg1 sample 302:307 a sample 300:307 a sample 300:307 A novel strictly anaerobic, thermotolerant, moderately halophilic, organotrophic bacterium, strain MRo-4T, was isolated from a sample of a microbial mat, developed under the flow of subsurface water in TauTona gold mine, South Africa. 27974092 14 17 theme 28179T=VKM 1665:1674 arg1 MRo-4T 1652:1657 MRo-4T 1652:1657 MRo-4T (=DSM 28179T=VKM B-2948T) 1652:1683 The type strain is MRo-4T (=DSM 28179T=VKM B-2948T). 27974092 14 17 theme 28179T=VKM 1665:1674 arg1 B-2948T 1676:1682 =DSM 28179T=VKM B-2948T 1660:1682 =DSM 28179T=VKM B-2948T 1660:1682 The type strain is MRo-4T (=DSM 28179T=VKM B-2948T). 27974092 3 18 theme novel 423:427 arg1 isolate 429:435 the novel isolate 419:435 the novel isolate 419:435 Cells of the novel isolate stained Gram-positive and were motile, spore-forming rods, 0.2-0.3 µm in width and 5-20 µm in length. 27974092 1 19 theme genus 149:153 arg1 Sporosalibacterium 155:172 the genus Sporosalibacterium 145:172 the genus Sporosalibacterium 145:172 nov., a thermotolerant, halophilic, hydrolytic bacterium isolated from a gold mine, and emended description of the genus Sporosalibacterium. 27974092 9 20 theme MRo-4T 1053:1058 arg1 sequences 1033:1041 16S rRNA gene sequences 1019:1041 16S rRNA gene sequences of strain MRo-4T and its nearest relatives 1019:1084 Phylogenetic analysis of 16S rRNA gene sequences of strain MRo-4T and its nearest relatives showed its affiliation to the genus Sporosalibacterium. 27974092 2 21 theme strain 267:272 arg1 bacterium 256:264 A novel strictly anaerobic, thermotolerant, moderately halophilic, organotrophic bacterium 175:264 A novel strictly anaerobic, thermotolerant, moderately halophilic, organotrophic bacterium 175:264 A novel strictly anaerobic, thermotolerant, moderately halophilic, organotrophic bacterium, strain MRo-4T, was isolated from a sample of a microbial mat, developed under the flow of subsurface water in TauTona gold mine, South Africa. 27974092 2 21 theme strain 267:272 arg1 MRo-4T 274:279 strain MRo-4T 267:279 strain MRo-4T 267:279 A novel strictly anaerobic, thermotolerant, moderately halophilic, organotrophic bacterium, strain MRo-4T, was isolated from a sample of a microbial mat, developed under the flow of subsurface water in TauTona gold mine, South Africa. 27974092 10 22 theme Sporosalibacteriumfaouarense 1142:1169 arg1 SOL3f37T 1171:1178 Sporosalibacteriumfaouarense SOL3f37T 1142:1178 Sporosalibacteriumfaouarense SOL3f37T 1142:1178 Sporosalibacteriumfaouarense SOL3f37T, the only valid published representative of the genus, appeared to be its closest relative (96.8 % 16S rRNA gene sequence similarity). 27974092 10 22 theme Sporosalibacteriumfaouarense 1142:1169 arg1 representative 1206:1219 the only valid published representative 1181:1219 the only valid published representative of the genus 1181:1232 Sporosalibacteriumfaouarense SOL3f37T, the only valid published representative of the genus, appeared to be its closest relative (96.8 % 16S rRNA gene sequence similarity). 27974092 1 23 theme Sporosalibacterium 155:172 arg1 description 130:140 emended description 122:140 emended description of the genus Sporosalibacterium 122:172 nov., a thermotolerant, halophilic, hydrolytic bacterium isolated from a gold mine, and emended description of the genus Sporosalibacterium. 27974092 1 23 theme Sporosalibacterium 155:172 arg1 bacterium 81:89 a thermotolerant, halophilic, hydrolytic bacterium 40:89 a thermotolerant, halophilic, hydrolytic bacterium isolated from a gold mine 40:115 nov., a thermotolerant, halophilic, hydrolytic bacterium isolated from a gold mine, and emended description of the genus Sporosalibacterium. 27974092 1 23 theme Sporosalibacterium 155:172 arg1 nov. 34:37 nov. 34:37 nov. 34:37 nov., a thermotolerant, halophilic, hydrolytic bacterium isolated from a gold mine, and emended description of the genus Sporosalibacterium. 27974092 10 24 theme rRNA 1283:1286 arg1 similarity 1302:1311 96.8 % 16S rRNA gene sequence similarity 1272:1311 96.8 % 16S rRNA gene sequence similarity 1272:1311 Sporosalibacteriumfaouarense SOL3f37T, the only valid published representative of the genus, appeared to be its closest relative (96.8 % 16S rRNA gene sequence similarity). 27974092 10 24 theme rRNA 1283:1286 arg1 relative 1262:1269 its closest relative 1250:1269 its closest relative (96.8 % 16S rRNA gene sequence similarity) 1250:1312 Sporosalibacteriumfaouarense SOL3f37T, the only valid published representative of the genus, appeared to be its closest relative (96.8 % 16S rRNA gene sequence similarity). 27974092 10 25 theme 16S 1279:1281 arg1 similarity 1302:1311 96.8 % 16S rRNA gene sequence similarity 1272:1311 96.8 % 16S rRNA gene sequence similarity 1272:1311 Sporosalibacteriumfaouarense SOL3f37T, the only valid published representative of the genus, appeared to be its closest relative (96.8 % 16S rRNA gene sequence similarity). 27974092 10 25 theme 16S 1279:1281 arg1 relative 1262:1269 its closest relative 1250:1269 its closest relative (96.8 % 16S rRNA gene sequence similarity) 1250:1312 Sporosalibacteriumfaouarense SOL3f37T, the only valid published representative of the genus, appeared to be its closest relative (96.8 % 16S rRNA gene sequence similarity). 27974092 11 26 dep strains 1324:1330 arg1 MRo-4T 1332:1337 MRo-4T 1332:1337 MRo-4T 1332:1337 However, strains MRo-4T and S. faouarense SOL3f37T differed in temperature, pH and salinity ranges for growth, requirement for yeast extract and substrate profiles. 27974092 11 26 dep strains 1324:1330 arg1 SOL3f37T 1357:1364 SOL3f37T 1357:1364 SOL3f37T 1357:1364 However, strains MRo-4T and S. faouarense SOL3f37T differed in temperature, pH and salinity ranges for growth, requirement for yeast extract and substrate profiles. 27974092 11 26 dep strains 1324:1330 arg1 strains 1324:1330 strains 1324:1330 strains MRo-4T and S. faouarense SOL3f37T 1324:1364 However, strains MRo-4T and S. faouarense SOL3f37T differed in temperature, pH and salinity ranges for growth, requirement for yeast extract and substrate profiles. 27974092 14 27 theme =DSM 1660:1663 arg1 MRo-4T 1652:1657 MRo-4T 1652:1657 MRo-4T (=DSM 28179T=VKM B-2948T) 1652:1683 The type strain is MRo-4T (=DSM 28179T=VKM B-2948T). 27974092 14 27 theme =DSM 1660:1663 arg1 B-2948T 1676:1682 =DSM 28179T=VKM B-2948T 1660:1682 =DSM 28179T=VKM B-2948T 1660:1682 The type strain is MRo-4T (=DSM 28179T=VKM B-2948T). 27974092 10 28 theme % 1277:1277 arg1 similarity 1302:1311 96.8 % 16S rRNA gene sequence similarity 1272:1311 96.8 % 16S rRNA gene sequence similarity 1272:1311 Sporosalibacteriumfaouarense SOL3f37T, the only valid published representative of the genus, appeared to be its closest relative (96.8 % 16S rRNA gene sequence similarity). 27974092 10 28 theme % 1277:1277 arg1 relative 1262:1269 its closest relative 1250:1269 its closest relative (96.8 % 16S rRNA gene sequence similarity) 1250:1312 Sporosalibacteriumfaouarense SOL3f37T, the only valid published representative of the genus, appeared to be its closest relative (96.8 % 16S rRNA gene sequence similarity). 27974092 3 29 dep motile 468:473 arg1 spore-forming 476:488 spore-forming 476:488 spore-forming 476:488 Cells of the novel isolate stained Gram-positive and were motile, spore-forming rods, 0.2-0.3 µm in width and 5-20 µm in length. 27974092 10 30 theme published 1196:1204 arg1 SOL3f37T 1171:1178 Sporosalibacteriumfaouarense SOL3f37T 1142:1178 Sporosalibacteriumfaouarense SOL3f37T 1142:1178 Sporosalibacteriumfaouarense SOL3f37T, the only valid published representative of the genus, appeared to be its closest relative (96.8 % 16S rRNA gene sequence similarity). 27974092 10 30 theme published 1196:1204 arg1 representative 1206:1219 the only valid published representative 1181:1219 the only valid published representative of the genus 1181:1232 Sporosalibacteriumfaouarense SOL3f37T, the only valid published representative of the genus, appeared to be its closest relative (96.8 % 16S rRNA gene sequence similarity). 27974092 4 31 theme NaCl 595:598 arg1 concentration 600:612 an NaCl concentration 592:612 an NaCl concentration of 5-100 g l-1 592:627 Strain MRo-4T grew at 25-50 °C, at pH 7.0-8.8 and at an NaCl concentration of 5-100 g l-1. 27974092 9 32 theme strain 1046:1051 arg1 MRo-4T 1053:1058 strain MRo-4T 1046:1058 strain MRo-4T 1046:1058 Phylogenetic analysis of 16S rRNA gene sequences of strain MRo-4T and its nearest relatives showed its affiliation to the genus Sporosalibacterium. 27974092 10 33 theme valid 1190:1194 arg1 SOL3f37T 1171:1178 Sporosalibacteriumfaouarense SOL3f37T 1142:1178 Sporosalibacteriumfaouarense SOL3f37T 1142:1178 Sporosalibacteriumfaouarense SOL3f37T, the only valid published representative of the genus, appeared to be its closest relative (96.8 % 16S rRNA gene sequence similarity). 27974092 10 33 theme valid 1190:1194 arg1 representative 1206:1219 the only valid published representative 1181:1219 the only valid published representative of the genus 1181:1232 Sporosalibacteriumfaouarense SOL3f37T, the only valid published representative of the genus, appeared to be its closest relative (96.8 % 16S rRNA gene sequence similarity). 27974092 10 34 theme 96.8  1272:1276 arg1 % 1277:1277 % 1277:1277 % 1277:1277 Sporosalibacteriumfaouarense SOL3f37T, the only valid published representative of the genus, appeared to be its closest relative (96.8 % 16S rRNA gene sequence similarity). 27974092 2 35 attach isolated 286:293 arg2 bacterium 256:264 A novel strictly anaerobic, thermotolerant, moderately halophilic, organotrophic bacterium 175:264 A novel strictly anaerobic, thermotolerant, moderately halophilic, organotrophic bacterium 175:264 A novel strictly anaerobic, thermotolerant, moderately halophilic, organotrophic bacterium, strain MRo-4T, was isolated from a sample of a microbial mat, developed under the flow of subsurface water in TauTona gold mine, South Africa. 27974092 2 35 attach isolated 286:293 arg2 MRo-4T 274:279 strain MRo-4T 267:279 strain MRo-4T 267:279 A novel strictly anaerobic, thermotolerant, moderately halophilic, organotrophic bacterium, strain MRo-4T, was isolated from a sample of a microbial mat, developed under the flow of subsurface water in TauTona gold mine, South Africa. 27974092 2 35 attach isolated 286:293 arg1 sample 302:307 a sample 300:307 a sample 300:307 A novel strictly anaerobic, thermotolerant, moderately halophilic, organotrophic bacterium, strain MRo-4T, was isolated from a sample of a microbial mat, developed under the flow of subsurface water in TauTona gold mine, South Africa. 27974092 9 36 theme relatives 1076:1084 arg1 sequences 1033:1041 16S rRNA gene sequences 1019:1041 16S rRNA gene sequences of strain MRo-4T and its nearest relatives 1019:1084 Phylogenetic analysis of 16S rRNA gene sequences of strain MRo-4T and its nearest relatives showed its affiliation to the genus Sporosalibacterium. 27974092 4 37 theme l-1 625:627 arg1 concentration 600:612 an NaCl concentration 592:612 an NaCl concentration of 5-100 g l-1 592:627 Strain MRo-4T grew at 25-50 °C, at pH 7.0-8.8 and at an NaCl concentration of 5-100 g l-1. 27974092 10 38 theme only 1185:1188 arg1 SOL3f37T 1171:1178 Sporosalibacteriumfaouarense SOL3f37T 1142:1178 Sporosalibacteriumfaouarense SOL3f37T 1142:1178 Sporosalibacteriumfaouarense SOL3f37T, the only valid published representative of the genus, appeared to be its closest relative (96.8 % 16S rRNA gene sequence similarity). 27974092 10 38 theme only 1185:1188 arg1 representative 1206:1219 the only valid published representative 1181:1219 the only valid published representative of the genus 1181:1232 Sporosalibacteriumfaouarense SOL3f37T, the only valid published representative of the genus, appeared to be its closest relative (96.8 % 16S rRNA gene sequence similarity). 27974092 1 39 dep thermotolerant 42:55 arg1 hydrolytic 70:79 hydrolytic 70:79 hydrolytic 70:79 nov., a thermotolerant, halophilic, hydrolytic bacterium isolated from a gold mine, and emended description of the genus Sporosalibacterium. 27974092 1 39 dep thermotolerant 42:55 arg1 halophilic 58:67 halophilic 58:67 halophilic 58:67 nov., a thermotolerant, halophilic, hydrolytic bacterium isolated from a gold mine, and emended description of the genus Sporosalibacterium. 27974092 12 40 theme isolate 1557:1563 arg1 analysis 1506:1513 the phylogenetic analysis 1489:1513 the phylogenetic analysis 1489:1513 Based on the phylogenetic analysis and physiological properties of the novel isolate, we propose a novel species, Sporosalibacterium tautonense sp. 27974092 12 40 theme isolate 1557:1563 arg1 properties 1533:1542 physiological properties 1519:1542 physiological properties 1519:1542 Based on the phylogenetic analysis and physiological properties of the novel isolate, we propose a novel species, Sporosalibacterium tautonense sp. 27974092 7 41 dep iso-C15  890:897 arg1 anteiso-C15  935:946 anteiso-C15  935:946 anteiso-C15  935:946 The major fatty acids were iso-C15 : 0, iso-C15 : 0 dimethyl acetyl and anteiso-C15 : 0. 27974092 7 41 dep iso-C15  890:897 arg1 acetyl 924:929  0 dimethyl acetyl 912:929  0 dimethyl acetyl 912:929 The major fatty acids were iso-C15 : 0, iso-C15 : 0 dimethyl acetyl and anteiso-C15 : 0. 27974092 7 41 dep iso-C15  890:897 arg1  0 899:900  0 899:900  0 899:900 The major fatty acids were iso-C15 : 0, iso-C15 : 0 dimethyl acetyl and anteiso-C15 : 0. 27974092 7 41 dep iso-C15  890:897 arg1  0 948:949  0 948:949  0 948:949 The major fatty acids were iso-C15 : 0, iso-C15 : 0 dimethyl acetyl and anteiso-C15 : 0. 27974092 9 42 theme Phylogenetic 994:1005 arg1 analysis 1007:1014 Phylogenetic analysis 994:1014 Phylogenetic analysis of 16S rRNA gene sequences of strain MRo-4T and its nearest relatives 994:1084 Phylogenetic analysis of 16S rRNA gene sequences of strain MRo-4T and its nearest relatives showed its affiliation to the genus Sporosalibacterium. 27974092 2 43 theme water 368:372 arg1 flow 349:352 the flow 345:352 the flow of subsurface water in TauTona gold mine, South Africa 345:407 A novel strictly anaerobic, thermotolerant, moderately halophilic, organotrophic bacterium, strain MRo-4T, was isolated from a sample of a microbial mat, developed under the flow of subsurface water in TauTona gold mine, South Africa. 27974092 1 44 attach isolated 91:98 arg2 bacterium 81:89 a thermotolerant, halophilic, hydrolytic bacterium 40:89 a thermotolerant, halophilic, hydrolytic bacterium isolated from a gold mine 40:115 nov., a thermotolerant, halophilic, hydrolytic bacterium isolated from a gold mine, and emended description of the genus Sporosalibacterium. 27974092 1 44 attach isolated 91:98 arg1 mine 112:115 a gold mine 105:115 a gold mine 105:115 nov., a thermotolerant, halophilic, hydrolytic bacterium isolated from a gold mine, and emended description of the genus Sporosalibacterium. 27974092 8 45 theme G+C 956:958 arg1 content 960:966 The G+C content 952:966 The G+C content of the DNA 952:977 The G+C content of the DNA was 32.9 mol%. 27974092 8 45 theme G+C 956:958 arg1 % 991:991 32.9 mol% 983:991 32.9 mol% 983:991 The G+C content of the DNA was 32.9 mol%. 27974092 10 46 theme genus 1228:1232 arg1 SOL3f37T 1171:1178 Sporosalibacteriumfaouarense SOL3f37T 1142:1178 Sporosalibacteriumfaouarense SOL3f37T 1142:1178 Sporosalibacteriumfaouarense SOL3f37T, the only valid published representative of the genus, appeared to be its closest relative (96.8 % 16S rRNA gene sequence similarity). 27974092 10 46 theme genus 1228:1232 arg1 representative 1206:1219 the only valid published representative 1181:1219 the only valid published representative of the genus 1181:1232 Sporosalibacteriumfaouarense SOL3f37T, the only valid published representative of the genus, appeared to be its closest relative (96.8 % 16S rRNA gene sequence similarity). 27974092 12 47 theme phylogenetic 1493:1504 arg1 analysis 1506:1513 the phylogenetic analysis 1489:1513 the phylogenetic analysis 1489:1513 Based on the phylogenetic analysis and physiological properties of the novel isolate, we propose a novel species, Sporosalibacterium tautonense sp. 27974092 14 48 theme type 1637:1640 arg1 MRo-4T 1652:1657 MRo-4T 1652:1657 MRo-4T (=DSM 28179T=VKM B-2948T) 1652:1683 The type strain is MRo-4T (=DSM 28179T=VKM B-2948T). 27974092 14 48 theme type 1637:1640 arg1 strain 1642:1647 The type strain 1633:1647 The type strain 1633:1647 The type strain is MRo-4T (=DSM 28179T=VKM B-2948T). 27974092 7 49 theme dimethyl 915:922 arg1 acetyl 924:929  0 dimethyl acetyl 912:929  0 dimethyl acetyl 912:929 The major fatty acids were iso-C15 : 0, iso-C15 : 0 dimethyl acetyl and anteiso-C15 : 0. 27974092 12 50 theme novel 1551:1555 arg1 isolate 1557:1563 the novel isolate 1547:1563 the novel isolate 1547:1563 Based on the phylogenetic analysis and physiological properties of the novel isolate, we propose a novel species, Sporosalibacterium tautonense sp. 27974092 2 51 from flow 349:352 arg1 Africa 402:407 Africa 402:407 Africa 402:407 A novel strictly anaerobic, thermotolerant, moderately halophilic, organotrophic bacterium, strain MRo-4T, was isolated from a sample of a microbial mat, developed under the flow of subsurface water in TauTona gold mine, South Africa. 27974092 2 51 from flow 349:352 arg1 South 396:400 South 396:400 South 396:400 A novel strictly anaerobic, thermotolerant, moderately halophilic, organotrophic bacterium, strain MRo-4T, was isolated from a sample of a microbial mat, developed under the flow of subsurface water in TauTona gold mine, South Africa. 27974092 1 52 theme gold 107:110 arg1 mine 112:115 a gold mine 105:115 a gold mine 105:115 nov., a thermotolerant, halophilic, hydrolytic bacterium isolated from a gold mine, and emended description of the genus Sporosalibacterium. 27974092 6 53 theme Elemental 756:764 arg1 sulfur 766:771 Elemental sulfur 756:771 Elemental sulfur 756:771 Elemental sulfur, thiosulfate, sulfate, sulfite, nitrate, nitrite, fumarate and arsenate were not reduced. 27974092 2 54 theme microbial 314:322 arg1 mat 324:326 a microbial mat 312:326 a microbial mat 312:326 A novel strictly anaerobic, thermotolerant, moderately halophilic, organotrophic bacterium, strain MRo-4T, was isolated from a sample of a microbial mat, developed under the flow of subsurface water in TauTona gold mine, South Africa. 27974092 3 55 from width 510:514 arg1 0.2-0.3 µm 496:505 0.2-0.3 µm 496:505 0.2-0.3 µm 496:505 Cells of the novel isolate stained Gram-positive and were motile, spore-forming rods, 0.2-0.3 µm in width and 5-20 µm in length. 27974092 9 56 theme nearest 1068:1074 arg1 relatives 1076:1084 its nearest relatives 1064:1084 its nearest relatives 1064:1084 Phylogenetic analysis of 16S rRNA gene sequences of strain MRo-4T and its nearest relatives showed its affiliation to the genus Sporosalibacterium. 27974092 2 57 theme anaerobic 192:200 arg1 bacterium 256:264 A novel strictly anaerobic, thermotolerant, moderately halophilic, organotrophic bacterium 175:264 A novel strictly anaerobic, thermotolerant, moderately halophilic, organotrophic bacterium 175:264 A novel strictly anaerobic, thermotolerant, moderately halophilic, organotrophic bacterium, strain MRo-4T, was isolated from a sample of a microbial mat, developed under the flow of subsurface water in TauTona gold mine, South Africa. 27974092 2 57 theme anaerobic 192:200 arg1 MRo-4T 274:279 strain MRo-4T 267:279 strain MRo-4T 267:279 A novel strictly anaerobic, thermotolerant, moderately halophilic, organotrophic bacterium, strain MRo-4T, was isolated from a sample of a microbial mat, developed under the flow of subsurface water in TauTona gold mine, South Africa. 27974092 9 58 theme sequences 1033:1041 arg1 analysis 1007:1014 Phylogenetic analysis 994:1014 Phylogenetic analysis of 16S rRNA gene sequences of strain MRo-4T and its nearest relatives 994:1084 Phylogenetic analysis of 16S rRNA gene sequences of strain MRo-4T and its nearest relatives showed its affiliation to the genus Sporosalibacterium. 27974092 3 59 theme isolate 429:435 arg1 Cells 410:414 Cells 410:414 Cells of the novel isolate 410:435 Cells of the novel isolate stained Gram-positive and were motile, spore-forming rods, 0.2-0.3 µm in width and 5-20 µm in length. 27974092 9 60 theme 16S 1019:1021 arg1 sequences 1033:1041 16S rRNA gene sequences 1019:1041 16S rRNA gene sequences of strain MRo-4T and its nearest relatives 1019:1084 Phylogenetic analysis of 16S rRNA gene sequences of strain MRo-4T and its nearest relatives showed its affiliation to the genus Sporosalibacterium. 27974092 12 61 dep sp 1624:1625 arg1 Sporosalibacterium 1594:1611 Sporosalibacterium 1594:1611 Sporosalibacterium 1594:1611 Based on the phylogenetic analysis and physiological properties of the novel isolate, we propose a novel species, Sporosalibacterium tautonense sp. 27974092 7 62 theme  0 912:913 arg1 acetyl 924:929  0 dimethyl acetyl 912:929  0 dimethyl acetyl 912:929 The major fatty acids were iso-C15 : 0, iso-C15 : 0 dimethyl acetyl and anteiso-C15 : 0. 27974092 9 63 theme genus 1116:1120 arg1 Sporosalibacterium 1122:1139 the genus Sporosalibacterium 1112:1139 the genus Sporosalibacterium 1112:1139 Phylogenetic analysis of 16S rRNA gene sequences of strain MRo-4T and its nearest relatives showed its affiliation to the genus Sporosalibacterium. 27974092 11 64 theme yeast 1442:1446 arg1 extract 1448:1454 yeast extract 1442:1454 yeast extract 1442:1454 However, strains MRo-4T and S. faouarense SOL3f37T differed in temperature, pH and salinity ranges for growth, requirement for yeast extract and substrate profiles. 27974092 3 65 from 5-20 µm 520:526 arg1 0.2-0.3 µm 496:505 0.2-0.3 µm 496:505 0.2-0.3 µm 496:505 Cells of the novel isolate stained Gram-positive and were motile, spore-forming rods, 0.2-0.3 µm in width and 5-20 µm in length. 27974092 12 66 theme physiological 1519:1531 arg1 properties 1533:1542 physiological properties 1519:1542 physiological properties 1519:1542 Based on the phylogenetic analysis and physiological properties of the novel isolate, we propose a novel species, Sporosalibacterium tautonense sp. 27974092 2 67 theme novel 177:181 arg1 bacterium 256:264 A novel strictly anaerobic, thermotolerant, moderately halophilic, organotrophic bacterium 175:264 A novel strictly anaerobic, thermotolerant, moderately halophilic, organotrophic bacterium 175:264 A novel strictly anaerobic, thermotolerant, moderately halophilic, organotrophic bacterium, strain MRo-4T, was isolated from a sample of a microbial mat, developed under the flow of subsurface water in TauTona gold mine, South Africa. 27974092 2 67 theme novel 177:181 arg1 MRo-4T 274:279 strain MRo-4T 267:279 strain MRo-4T 267:279 A novel strictly anaerobic, thermotolerant, moderately halophilic, organotrophic bacterium, strain MRo-4T, was isolated from a sample of a microbial mat, developed under the flow of subsurface water in TauTona gold mine, South Africa. 27974092 12 68 theme tautonense 1613:1622 arg1 sp 1624:1625 tautonense sp 1613:1625 tautonense sp 1613:1625 Based on the phylogenetic analysis and physiological properties of the novel isolate, we propose a novel species, Sporosalibacterium tautonense sp. 27974092 1 69 theme emended 122:128 arg1 description 130:140 emended description 122:140 emended description of the genus Sporosalibacterium 122:172 nov., a thermotolerant, halophilic, hydrolytic bacterium isolated from a gold mine, and emended description of the genus Sporosalibacterium. 27974092 2 70 theme subsurface 357:366 arg1 water 368:372 subsurface water 357:372 subsurface water 357:372 A novel strictly anaerobic, thermotolerant, moderately halophilic, organotrophic bacterium, strain MRo-4T, was isolated from a sample of a microbial mat, developed under the flow of subsurface water in TauTona gold mine, South Africa. 27974092 8 71 theme 32.9 mol 983:990 arg1 content 960:966 The G+C content 952:966 The G+C content of the DNA 952:977 The G+C content of the DNA was 32.9 mol%. 27974092 8 71 theme 32.9 mol 983:990 arg1 % 991:991 32.9 mol% 983:991 32.9 mol% 983:991 The G+C content of the DNA was 32.9 mol%. 27974092 1 72 theme thermotolerant 42:55 arg1 bacterium 81:89 a thermotolerant, halophilic, hydrolytic bacterium 40:89 a thermotolerant, halophilic, hydrolytic bacterium isolated from a gold mine 40:115 nov., a thermotolerant, halophilic, hydrolytic bacterium isolated from a gold mine, and emended description of the genus Sporosalibacterium. 27974092 7 73 theme fatty 873:877 arg1 iso-C15  890:897 iso-C15  890:897 iso-C15  890:897 The major fatty acids were iso-C15 : 0, iso-C15 : 0 dimethyl acetyl and anteiso-C15 : 0. 27974092 7 73 theme fatty 873:877 arg1 acids 879:883 The major fatty acids 863:883 The major fatty acids 863:883 The major fatty acids were iso-C15 : 0, iso-C15 : 0 dimethyl acetyl and anteiso-C15 : 0. 27974092 3 74 from rods 490:493 arg1 length 531:536 length 531:536 length 531:536 Cells of the novel isolate stained Gram-positive and were motile, spore-forming rods, 0.2-0.3 µm in width and 5-20 µm in length. 27974092 2 75 dep anaerobic 192:200 arg1 organotrophic 242:254 organotrophic 242:254 organotrophic 242:254 A novel strictly anaerobic, thermotolerant, moderately halophilic, organotrophic bacterium, strain MRo-4T, was isolated from a sample of a microbial mat, developed under the flow of subsurface water in TauTona gold mine, South Africa. 27974092 2 75 dep anaerobic 192:200 arg1 thermotolerant 203:216 thermotolerant 203:216 thermotolerant 203:216 A novel strictly anaerobic, thermotolerant, moderately halophilic, organotrophic bacterium, strain MRo-4T, was isolated from a sample of a microbial mat, developed under the flow of subsurface water in TauTona gold mine, South Africa. 27974092 2 75 dep anaerobic 192:200 arg1 halophilic 230:239 halophilic 230:239 halophilic 230:239 A novel strictly anaerobic, thermotolerant, moderately halophilic, organotrophic bacterium, strain MRo-4T, was isolated from a sample of a microbial mat, developed under the flow of subsurface water in TauTona gold mine, South Africa. 27442806 6 0 theme low-fat 905:911 arg1 sausage 965:971 a quinoa low-fat (LF; 85% of fat replacement; 4.5% of pork back-fat) sausage 896:971 a quinoa low-fat (LF; 85% of fat replacement; 4.5% of pork back-fat) sausage 896:971 Three types of sausages were prepared: a control (C; no fat replacement; 30% of pork back-fat), a quinoa half-fat (50% of fat replacement; 15% of pork back-fat), and a quinoa low-fat (LF; 85% of fat replacement; 4.5% of pork back-fat) sausage. 27442806 10 1 theme P 1462:1462 arg1 sausages 1452:1459 C sausages 1450:1459 C sausages (P < 0.05) 1450:1470 Furthermore, the descriptive sensory analysis showed a higher pungent flavor and lower juiciness in LF sausages than in C sausages (P < 0.05). 27442806 10 1 theme P 1462:1462 arg1 < 1464:1464 P < 0.05 1462:1469 P < 0.05 1462:1469 Furthermore, the descriptive sensory analysis showed a higher pungent flavor and lower juiciness in LF sausages than in C sausages (P < 0.05). 27442806 9 2 theme protein 1194:1200 arg1 content 1202:1208 protein content 1194:1208 protein content 1194:1208 Fat reduction resulted in higher aw , protein content, hardness, chewiness and redness values and spice-derived volatile levels, and in lower cohesiveness values (P < 0.05). 27442806 6 3 theme replacement 790:800 arg1 back-fat 815:822 pork back-fat 810:822 pork back-fat 810:822 Three types of sausages were prepared: a control (C; no fat replacement; 30% of pork back-fat), a quinoa half-fat (50% of fat replacement; 15% of pork back-fat), and a quinoa low-fat (LF; 85% of fat replacement; 4.5% of pork back-fat) sausage. 27442806 6 3 theme replacement 790:800 arg1 % 805:805 no fat replacement; 30% 783:805 no fat replacement; 30% of pork back-fat 783:822 Three types of sausages were prepared: a control (C; no fat replacement; 30% of pork back-fat), a quinoa half-fat (50% of fat replacement; 15% of pork back-fat), and a quinoa low-fat (LF; 85% of fat replacement; 4.5% of pork back-fat) sausage. 27442806 6 4 theme back-fat 955:962 arg1 % 945:945 4.5% 942:945 LF; 85% of fat replacement; 4.5% of pork back-fat 914:962 Three types of sausages were prepared: a control (C; no fat replacement; 30% of pork back-fat), a quinoa half-fat (50% of fat replacement; 15% of pork back-fat), and a quinoa low-fat (LF; 85% of fat replacement; 4.5% of pork back-fat) sausage. 27442806 6 4 theme back-fat 955:962 arg1 back-fat 955:962 pork back-fat 950:962 pork back-fat 950:962 Three types of sausages were prepared: a control (C; no fat replacement; 30% of pork back-fat), a quinoa half-fat (50% of fat replacement; 15% of pork back-fat), and a quinoa low-fat (LF; 85% of fat replacement; 4.5% of pork back-fat) sausage. 27442806 5 5 from effect 626:631 arg1 characteristics 675:689 the quality characteristics 663:689 the quality characteristics of a small diameter dry-cured sausage 663:727 The aim of this study was to assess the effect of replacing fat by quinoa on the quality characteristics of a small diameter dry-cured sausage. 27442806 4 6 theme nutritive 489:497 arg1 value 499:503 high nutritive value 484:503 high nutritive value 484:503 Quinua is a starchy seed with high nutritive value, which contains substances of technological interest in dry-cured manufacturing. 27442806 10 7 theme sensory 1359:1365 arg1 analysis 1367:1374 the descriptive sensory analysis 1343:1374 the descriptive sensory analysis 1343:1374 Furthermore, the descriptive sensory analysis showed a higher pungent flavor and lower juiciness in LF sausages than in C sausages (P < 0.05). 27442806 6 8 theme quinoa 828:833 arg1 half-fat 835:842 a quinoa half-fat 826:842 a quinoa half-fat (50% of fat replacement; 15% of pork back-fat) 826:889 Three types of sausages were prepared: a control (C; no fat replacement; 30% of pork back-fat), a quinoa half-fat (50% of fat replacement; 15% of pork back-fat), and a quinoa low-fat (LF; 85% of fat replacement; 4.5% of pork back-fat) sausage. 27442806 6 9 theme replacement 929:939 arg1 % 920:920 85% 918:920 LF; 85% of fat replacement; 4.5% of pork back-fat 914:962 Three types of sausages were prepared: a control (C; no fat replacement; 30% of pork back-fat), a quinoa half-fat (50% of fat replacement; 15% of pork back-fat), and a quinoa low-fat (LF; 85% of fat replacement; 4.5% of pork back-fat) sausage. 27442806 6 9 theme replacement 929:939 arg1 replacement 929:939 fat replacement 925:939 fat replacement 925:939 Three types of sausages were prepared: a control (C; no fat replacement; 30% of pork back-fat), a quinoa half-fat (50% of fat replacement; 15% of pork back-fat), and a quinoa low-fat (LF; 85% of fat replacement; 4.5% of pork back-fat) sausage. 27442806 4 10 theme dry-cured 561:569 arg1 manufacturing 571:583 dry-cured manufacturing 561:583 dry-cured manufacturing 561:583 Quinua is a starchy seed with high nutritive value, which contains substances of technological interest in dry-cured manufacturing. 27442806 7 11 theme microbial 1015:1023 arg1 composition 1025:1035 microbial composition 1015:1035 microbial composition 1015:1035 Sausages were analyzed for proximate and microbial composition, volatile compounds, and instrumental texture and color. 27442806 1 12 theme dry-cured 184:192 arg1 sausages 194:201 dry-cured sausages 184:201 dry-cured sausages 184:201 Different approaches have been previously studied in order to reduce the fat content of dry-cured sausages. 27442806 10 13 theme higher 1385:1390 arg1 flavor 1400:1405 a higher pungent flavor 1383:1405 a higher pungent flavor 1383:1405 Furthermore, the descriptive sensory analysis showed a higher pungent flavor and lower juiciness in LF sausages than in C sausages (P < 0.05). 27442806 11 14 theme decreased 1538:1546 arg1 acceptance 1556:1565 a decreased overall acceptance 1536:1565 a decreased overall acceptance of the sausages by consumers 1536:1594 In spite of those differences, fat reduction did not result in a decreased overall acceptance of the sausages by consumers. 27442806 5 15 theme replacing 636:644 arg1 fat 646:648 replacing fat 636:648 replacing fat by quinoa 636:658 The aim of this study was to assess the effect of replacing fat by quinoa on the quality characteristics of a small diameter dry-cured sausage. 27442806 4 16 contain contains 512:519 arg1 Quinua 454:459 Quinua 454:459 Quinua 454:459 Quinua is a starchy seed with high nutritive value, which contains substances of technological interest in dry-cured manufacturing. 27442806 4 16 contain contains 512:519 arg1 starchy 466:472 a starchy 464:472 a starchy 464:472 Quinua is a starchy seed with high nutritive value, which contains substances of technological interest in dry-cured manufacturing. 27442806 4 16 contain contains 512:519 arg2 substances 521:530 substances 521:530 substances of technological interest in dry-cured manufacturing 521:583 Quinua is a starchy seed with high nutritive value, which contains substances of technological interest in dry-cured manufacturing. 27442806 9 17 theme spice-derived 1254:1266 arg1 levels 1277:1282 spice-derived volatile levels 1254:1282 spice-derived volatile levels 1254:1282 Fat reduction resulted in higher aw , protein content, hardness, chewiness and redness values and spice-derived volatile levels, and in lower cohesiveness values (P < 0.05). 27442806 6 18 theme back-fat 815:822 arg1 back-fat 815:822 pork back-fat 810:822 pork back-fat 810:822 Three types of sausages were prepared: a control (C; no fat replacement; 30% of pork back-fat), a quinoa half-fat (50% of fat replacement; 15% of pork back-fat), and a quinoa low-fat (LF; 85% of fat replacement; 4.5% of pork back-fat) sausage. 27442806 6 18 theme back-fat 815:822 arg1 % 805:805 no fat replacement; 30% 783:805 no fat replacement; 30% of pork back-fat 783:822 Three types of sausages were prepared: a control (C; no fat replacement; 30% of pork back-fat), a quinoa half-fat (50% of fat replacement; 15% of pork back-fat), and a quinoa low-fat (LF; 85% of fat replacement; 4.5% of pork back-fat) sausage. 27442806 2 19 theme polysaccharides 227:241 arg1 use 220:222 the use 216:222 the use of polysaccharides, such as fiber, gums, or starch, 216:274 Among them, the use of polysaccharides, such as fiber, gums, or starch, have been proposed for fat replacing. 27442806 8 20 theme Descriptive 1094:1104 arg1 analyses 1126:1133 Descriptive and hedonic sensory analyses 1094:1133 Descriptive and hedonic sensory analyses 1094:1133 Descriptive and hedonic sensory analyses were also performed. 27442806 5 21 theme quality 667:673 arg1 characteristics 675:689 the quality characteristics 663:689 the quality characteristics of a small diameter dry-cured sausage 663:727 The aim of this study was to assess the effect of replacing fat by quinoa on the quality characteristics of a small diameter dry-cured sausage. 27442806 9 22 theme lower 1292:1296 arg1 < 1321:1321 P < 0.05 1319:1326 P < 0.05 1319:1326 Fat reduction resulted in higher aw , protein content, hardness, chewiness and redness values and spice-derived volatile levels, and in lower cohesiveness values (P < 0.05). 27442806 9 22 theme lower 1292:1296 arg1 values 1311:1316 lower cohesiveness values 1292:1316 lower cohesiveness values (P < 0.05) 1292:1327 Fat reduction resulted in higher aw , protein content, hardness, chewiness and redness values and spice-derived volatile levels, and in lower cohesiveness values (P < 0.05). 27442806 6 23 theme fat 852:854 arg1 replacement 856:866 fat replacement 852:866 fat replacement 852:866 Three types of sausages were prepared: a control (C; no fat replacement; 30% of pork back-fat), a quinoa half-fat (50% of fat replacement; 15% of pork back-fat), and a quinoa low-fat (LF; 85% of fat replacement; 4.5% of pork back-fat) sausage. 27442806 0 24 from Replacement 12:22 arg1 Characteristics 56:70 the Quality Characteristics 44:70 the Quality Characteristics of a Dry-Cured Sausage 44:93 Partial Fat Replacement by Boiled Quinoa on the Quality Characteristics of a Dry-Cured Sausage. 27442806 8 25 theme hedonic 1110:1116 arg1 analyses 1126:1133 Descriptive and hedonic sensory analyses 1094:1133 Descriptive and hedonic sensory analyses 1094:1133 Descriptive and hedonic sensory analyses were also performed. 27442806 4 26 from substances 521:530 arg1 manufacturing 571:583 dry-cured manufacturing 561:583 dry-cured manufacturing 561:583 Quinua is a starchy seed with high nutritive value, which contains substances of technological interest in dry-cured manufacturing. 27442806 9 27 link spice-derived 1254:1266 arg1 levels 1277:1282 spice-derived volatile levels 1254:1282 spice-derived volatile levels 1254:1282 Fat reduction resulted in higher aw , protein content, hardness, chewiness and redness values and spice-derived volatile levels, and in lower cohesiveness values (P < 0.05). 27442806 6 28 dep % 847:847 arg1 % 871:871 15% 869:871 50% of fat replacement; 15% of pork back-fat 845:888 Three types of sausages were prepared: a control (C; no fat replacement; 30% of pork back-fat), a quinoa half-fat (50% of fat replacement; 15% of pork back-fat), and a quinoa low-fat (LF; 85% of fat replacement; 4.5% of pork back-fat) sausage. 27442806 6 28 dep % 847:847 arg1 back-fat 881:888 pork back-fat 876:888 pork back-fat 876:888 Three types of sausages were prepared: a control (C; no fat replacement; 30% of pork back-fat), a quinoa half-fat (50% of fat replacement; 15% of pork back-fat), and a quinoa low-fat (LF; 85% of fat replacement; 4.5% of pork back-fat) sausage. 27442806 0 29 theme Dry-Cured 77:85 arg1 Sausage 87:93 a Dry-Cured Sausage 75:93 a Dry-Cured Sausage 75:93 Partial Fat Replacement by Boiled Quinoa on the Quality Characteristics of a Dry-Cured Sausage. 27442806 9 30 theme P 1319:1319 arg1 < 1321:1321 P < 0.05 1319:1326 P < 0.05 1319:1326 Fat reduction resulted in higher aw , protein content, hardness, chewiness and redness values and spice-derived volatile levels, and in lower cohesiveness values (P < 0.05). 27442806 9 30 theme P 1319:1319 arg1 values 1311:1316 lower cohesiveness values 1292:1316 lower cohesiveness values (P < 0.05) 1292:1327 Fat reduction resulted in higher aw , protein content, hardness, chewiness and redness values and spice-derived volatile levels, and in lower cohesiveness values (P < 0.05). 27442806 3 31 theme starchy 359:365 arg1 vegetables 378:387 vegetables 378:387 vegetables 378:387 Although scarcely studied, it is likely that starchy grains and vegetables might also be used as potential fat replacers in those sausages. 27442806 3 31 theme starchy 359:365 arg1 replacers 425:433 potential fat replacers 411:433 potential fat replacers in those sausages 411:451 Although scarcely studied, it is likely that starchy grains and vegetables might also be used as potential fat replacers in those sausages. 27442806 3 31 theme starchy 359:365 arg1 grains 367:372 starchy grains 359:372 starchy grains 359:372 Although scarcely studied, it is likely that starchy grains and vegetables might also be used as potential fat replacers in those sausages. 27442806 0 32 theme Partial 0:6 arg1 Replacement 12:22 Partial Fat Replacement 0:22 Partial Fat Replacement by Boiled Quinoa on the Quality Characteristics of a Dry-Cured Sausage 0:93 Partial Fat Replacement by Boiled Quinoa on the Quality Characteristics of a Dry-Cured Sausage. 27442806 3 33 used used 403:406 arg2 replacers 425:433 potential fat replacers 411:433 potential fat replacers in those sausages 411:451 Although scarcely studied, it is likely that starchy grains and vegetables might also be used as potential fat replacers in those sausages. 27442806 3 33 used used 403:406 arg2 vegetables 378:387 vegetables 378:387 vegetables 378:387 Although scarcely studied, it is likely that starchy grains and vegetables might also be used as potential fat replacers in those sausages. 27442806 3 33 used used 403:406 arg2 grains 367:372 starchy grains 359:372 starchy grains 359:372 Although scarcely studied, it is likely that starchy grains and vegetables might also be used as potential fat replacers in those sausages. 27442806 1 34 theme Different 96:104 arg1 approaches 106:115 Different approaches 96:115 Different approaches 96:115 Different approaches have been previously studied in order to reduce the fat content of dry-cured sausages. 27442806 6 35 theme pork 876:879 arg1 back-fat 881:888 pork back-fat 876:888 pork back-fat 876:888 Three types of sausages were prepared: a control (C; no fat replacement; 30% of pork back-fat), a quinoa half-fat (50% of fat replacement; 15% of pork back-fat), and a quinoa low-fat (LF; 85% of fat replacement; 4.5% of pork back-fat) sausage. 27442806 4 36 theme high 484:487 arg1 value 499:503 high nutritive value 484:503 high nutritive value 484:503 Quinua is a starchy seed with high nutritive value, which contains substances of technological interest in dry-cured manufacturing. 27442806 6 37 dep low-fat 905:911 arg1 LF 914:915 LF 914:915 LF; 85% of fat replacement; 4.5% of pork back-fat 914:962 Three types of sausages were prepared: a control (C; no fat replacement; 30% of pork back-fat), a quinoa half-fat (50% of fat replacement; 15% of pork back-fat), and a quinoa low-fat (LF; 85% of fat replacement; 4.5% of pork back-fat) sausage. 27442806 10 38 theme LF 1430:1431 arg1 sausages 1433:1440 LF sausages 1430:1440 LF sausages 1430:1440 Furthermore, the descriptive sensory analysis showed a higher pungent flavor and lower juiciness in LF sausages than in C sausages (P < 0.05). 27442806 5 39 theme small 696:700 arg1 sausage 721:727 a small diameter dry-cured sausage 694:727 a small diameter dry-cured sausage 694:727 The aim of this study was to assess the effect of replacing fat by quinoa on the quality characteristics of a small diameter dry-cured sausage. 27442806 0 40 theme Boiled 27:32 arg1 Quinoa 34:39 Boiled Quinoa 27:39 Boiled Quinoa 27:39 Partial Fat Replacement by Boiled Quinoa on the Quality Characteristics of a Dry-Cured Sausage. 27442806 0 41 theme Quality 48:54 arg1 Characteristics 56:70 the Quality Characteristics 44:70 the Quality Characteristics of a Dry-Cured Sausage 44:93 Partial Fat Replacement by Boiled Quinoa on the Quality Characteristics of a Dry-Cured Sausage. 27442806 6 42 dep LF 914:915 arg1 % 920:920 85% 918:920 LF; 85% of fat replacement; 4.5% of pork back-fat 914:962 Three types of sausages were prepared: a control (C; no fat replacement; 30% of pork back-fat), a quinoa half-fat (50% of fat replacement; 15% of pork back-fat), and a quinoa low-fat (LF; 85% of fat replacement; 4.5% of pork back-fat) sausage. 27442806 6 42 dep LF 914:915 arg1 replacement 929:939 fat replacement 925:939 fat replacement 925:939 Three types of sausages were prepared: a control (C; no fat replacement; 30% of pork back-fat), a quinoa half-fat (50% of fat replacement; 15% of pork back-fat), and a quinoa low-fat (LF; 85% of fat replacement; 4.5% of pork back-fat) sausage. 27442806 6 42 dep LF 914:915 arg1 % 945:945 4.5% 942:945 LF; 85% of fat replacement; 4.5% of pork back-fat 914:962 Three types of sausages were prepared: a control (C; no fat replacement; 30% of pork back-fat), a quinoa half-fat (50% of fat replacement; 15% of pork back-fat), and a quinoa low-fat (LF; 85% of fat replacement; 4.5% of pork back-fat) sausage. 27442806 6 42 dep LF 914:915 arg1 back-fat 955:962 pork back-fat 950:962 pork back-fat 950:962 Three types of sausages were prepared: a control (C; no fat replacement; 30% of pork back-fat), a quinoa half-fat (50% of fat replacement; 15% of pork back-fat), and a quinoa low-fat (LF; 85% of fat replacement; 4.5% of pork back-fat) sausage. 27442806 3 43 theme fat 421:423 arg1 vegetables 378:387 vegetables 378:387 vegetables 378:387 Although scarcely studied, it is likely that starchy grains and vegetables might also be used as potential fat replacers in those sausages. 27442806 3 43 theme fat 421:423 arg1 replacers 425:433 potential fat replacers 411:433 potential fat replacers in those sausages 411:451 Although scarcely studied, it is likely that starchy grains and vegetables might also be used as potential fat replacers in those sausages. 27442806 3 43 theme fat 421:423 arg1 grains 367:372 starchy grains 359:372 starchy grains 359:372 Although scarcely studied, it is likely that starchy grains and vegetables might also be used as potential fat replacers in those sausages. 27442806 5 44 theme dry-cured 711:719 arg1 sausage 721:727 a small diameter dry-cured sausage 694:727 a small diameter dry-cured sausage 694:727 The aim of this study was to assess the effect of replacing fat by quinoa on the quality characteristics of a small diameter dry-cured sausage. 27442806 9 45 theme Fat 1156:1158 arg1 reduction 1160:1168 Fat reduction 1156:1168 Fat reduction 1156:1168 Fat reduction resulted in higher aw , protein content, hardness, chewiness and redness values and spice-derived volatile levels, and in lower cohesiveness values (P < 0.05). 27442806 10 46 from juiciness 1417:1425 arg1 sausages 1433:1440 LF sausages 1430:1440 LF sausages 1430:1440 Furthermore, the descriptive sensory analysis showed a higher pungent flavor and lower juiciness in LF sausages than in C sausages (P < 0.05). 27442806 6 47 dep control 771:777 arg1 C 780:780 C 780:780 C 780:780 Three types of sausages were prepared: a control (C; no fat replacement; 30% of pork back-fat), a quinoa half-fat (50% of fat replacement; 15% of pork back-fat), and a quinoa low-fat (LF; 85% of fat replacement; 4.5% of pork back-fat) sausage. 27442806 10 48 theme C 1450:1450 arg1 sausages 1452:1459 C sausages 1450:1459 C sausages (P < 0.05) 1450:1470 Furthermore, the descriptive sensory analysis showed a higher pungent flavor and lower juiciness in LF sausages than in C sausages (P < 0.05). 27442806 10 48 theme C 1450:1450 arg1 < 1464:1464 P < 0.05 1462:1469 P < 0.05 1462:1469 Furthermore, the descriptive sensory analysis showed a higher pungent flavor and lower juiciness in LF sausages than in C sausages (P < 0.05). 27442806 6 49 theme sausages 745:752 arg1 types 736:740 Three types 730:740 Three types of sausages 730:752 Three types of sausages were prepared: a control (C; no fat replacement; 30% of pork back-fat), a quinoa half-fat (50% of fat replacement; 15% of pork back-fat), and a quinoa low-fat (LF; 85% of fat replacement; 4.5% of pork back-fat) sausage. 27442806 6 50 dep C 780:780 arg1 back-fat 815:822 pork back-fat 810:822 pork back-fat 810:822 Three types of sausages were prepared: a control (C; no fat replacement; 30% of pork back-fat), a quinoa half-fat (50% of fat replacement; 15% of pork back-fat), and a quinoa low-fat (LF; 85% of fat replacement; 4.5% of pork back-fat) sausage. 27442806 6 50 dep C 780:780 arg1 % 805:805 no fat replacement; 30% 783:805 no fat replacement; 30% of pork back-fat 783:822 Three types of sausages were prepared: a control (C; no fat replacement; 30% of pork back-fat), a quinoa half-fat (50% of fat replacement; 15% of pork back-fat), and a quinoa low-fat (LF; 85% of fat replacement; 4.5% of pork back-fat) sausage. 27442806 4 51 theme technological 535:547 arg1 interest 549:556 technological interest 535:556 technological interest 535:556 Quinua is a starchy seed with high nutritive value, which contains substances of technological interest in dry-cured manufacturing. 27442806 6 52 theme quinoa 898:903 arg1 low-fat 905:911 a quinoa low-fat 896:911 a quinoa low-fat (LF; 85% of fat replacement; 4.5% of pork back-fat) sausage 896:971 Three types of sausages were prepared: a control (C; no fat replacement; 30% of pork back-fat), a quinoa half-fat (50% of fat replacement; 15% of pork back-fat), and a quinoa low-fat (LF; 85% of fat replacement; 4.5% of pork back-fat) sausage. 27442806 9 53 theme content 1202:1208 arg1 values 1243:1248 aw , protein content, hardness, chewiness and redness values 1189:1248 aw , protein content, hardness, chewiness and redness values 1189:1248 Fat reduction resulted in higher aw , protein content, hardness, chewiness and redness values and spice-derived volatile levels, and in lower cohesiveness values (P < 0.05). 27442806 6 54 theme fat 786:788 arg1 back-fat 815:822 pork back-fat 810:822 pork back-fat 810:822 Three types of sausages were prepared: a control (C; no fat replacement; 30% of pork back-fat), a quinoa half-fat (50% of fat replacement; 15% of pork back-fat), and a quinoa low-fat (LF; 85% of fat replacement; 4.5% of pork back-fat) sausage. 27442806 6 54 theme fat 786:788 arg1 % 805:805 no fat replacement; 30% 783:805 no fat replacement; 30% of pork back-fat 783:822 Three types of sausages were prepared: a control (C; no fat replacement; 30% of pork back-fat), a quinoa half-fat (50% of fat replacement; 15% of pork back-fat), and a quinoa low-fat (LF; 85% of fat replacement; 4.5% of pork back-fat) sausage. 27442806 6 55 theme pork 950:953 arg1 back-fat 955:962 pork back-fat 950:962 pork back-fat 950:962 Three types of sausages were prepared: a control (C; no fat replacement; 30% of pork back-fat), a quinoa half-fat (50% of fat replacement; 15% of pork back-fat), and a quinoa low-fat (LF; 85% of fat replacement; 4.5% of pork back-fat) sausage. 27442806 9 56 theme chewiness 1221:1229 arg1 values 1243:1248 aw , protein content, hardness, chewiness and redness values 1189:1248 aw , protein content, hardness, chewiness and redness values 1189:1248 Fat reduction resulted in higher aw , protein content, hardness, chewiness and redness values and spice-derived volatile levels, and in lower cohesiveness values (P < 0.05). 27442806 9 57 theme hardness 1211:1218 arg1 values 1243:1248 aw , protein content, hardness, chewiness and redness values 1189:1248 aw , protein content, hardness, chewiness and redness values 1189:1248 Fat reduction resulted in higher aw , protein content, hardness, chewiness and redness values and spice-derived volatile levels, and in lower cohesiveness values (P < 0.05). 27442806 1 58 theme fat 169:171 arg1 content 173:179 the fat content 165:179 the fat content of dry-cured sausages 165:201 Different approaches have been previously studied in order to reduce the fat content of dry-cured sausages. 27442806 10 59 theme descriptive 1347:1357 arg1 analysis 1367:1374 the descriptive sensory analysis 1343:1374 the descriptive sensory analysis 1343:1374 Furthermore, the descriptive sensory analysis showed a higher pungent flavor and lower juiciness in LF sausages than in C sausages (P < 0.05). 27442806 3 60 from replacers 425:433 arg1 sausages 444:451 those sausages 438:451 those sausages 438:451 Although scarcely studied, it is likely that starchy grains and vegetables might also be used as potential fat replacers in those sausages. 27442806 9 61 theme redness 1235:1241 arg1 values 1243:1248 aw , protein content, hardness, chewiness and redness values 1189:1248 aw , protein content, hardness, chewiness and redness values 1189:1248 Fat reduction resulted in higher aw , protein content, hardness, chewiness and redness values and spice-derived volatile levels, and in lower cohesiveness values (P < 0.05). 27442806 9 62 dep higher 1182:1187 arg1 values 1243:1248 aw , protein content, hardness, chewiness and redness values 1189:1248 aw , protein content, hardness, chewiness and redness values 1189:1248 Fat reduction resulted in higher aw , protein content, hardness, chewiness and redness values and spice-derived volatile levels, and in lower cohesiveness values (P < 0.05). 27442806 6 63 theme fat 925:927 arg1 replacement 929:939 fat replacement 925:939 fat replacement 925:939 Three types of sausages were prepared: a control (C; no fat replacement; 30% of pork back-fat), a quinoa half-fat (50% of fat replacement; 15% of pork back-fat), and a quinoa low-fat (LF; 85% of fat replacement; 4.5% of pork back-fat) sausage. 27442806 10 64 theme pungent 1392:1398 arg1 flavor 1400:1405 a higher pungent flavor 1383:1405 a higher pungent flavor 1383:1405 Furthermore, the descriptive sensory analysis showed a higher pungent flavor and lower juiciness in LF sausages than in C sausages (P < 0.05). 27442806 1 65 theme sausages 194:201 arg1 content 173:179 the fat content 165:179 the fat content of dry-cured sausages 165:201 Different approaches have been previously studied in order to reduce the fat content of dry-cured sausages. 27442806 5 66 theme fat 646:648 arg1 effect 626:631 the effect 622:631 the effect of replacing fat by quinoa on the quality characteristics of a small diameter dry-cured sausage 622:727 The aim of this study was to assess the effect of replacing fat by quinoa on the quality characteristics of a small diameter dry-cured sausage. 27442806 5 67 theme study 602:606 arg1 aim 590:592 The aim 586:592 The aim of this study 586:606 The aim of this study was to assess the effect of replacing fat by quinoa on the quality characteristics of a small diameter dry-cured sausage. 27442806 9 68 theme volatile 1268:1275 arg1 levels 1277:1282 spice-derived volatile levels 1254:1282 spice-derived volatile levels 1254:1282 Fat reduction resulted in higher aw , protein content, hardness, chewiness and redness values and spice-derived volatile levels, and in lower cohesiveness values (P < 0.05). 27442806 6 69 theme pork 810:813 arg1 back-fat 815:822 pork back-fat 810:822 pork back-fat 810:822 Three types of sausages were prepared: a control (C; no fat replacement; 30% of pork back-fat), a quinoa half-fat (50% of fat replacement; 15% of pork back-fat), and a quinoa low-fat (LF; 85% of fat replacement; 4.5% of pork back-fat) sausage. 27442806 6 70 dep half-fat 835:842 arg1 % 847:847 50% 845:847 50% of fat replacement; 15% of pork back-fat 845:888 Three types of sausages were prepared: a control (C; no fat replacement; 30% of pork back-fat), a quinoa half-fat (50% of fat replacement; 15% of pork back-fat), and a quinoa low-fat (LF; 85% of fat replacement; 4.5% of pork back-fat) sausage. 27442806 6 70 dep half-fat 835:842 arg1 replacement 856:866 fat replacement 852:866 fat replacement 852:866 Three types of sausages were prepared: a control (C; no fat replacement; 30% of pork back-fat), a quinoa half-fat (50% of fat replacement; 15% of pork back-fat), and a quinoa low-fat (LF; 85% of fat replacement; 4.5% of pork back-fat) sausage. 27442806 6 71 theme replacement 856:866 arg1 % 847:847 50% 845:847 50% of fat replacement; 15% of pork back-fat 845:888 Three types of sausages were prepared: a control (C; no fat replacement; 30% of pork back-fat), a quinoa half-fat (50% of fat replacement; 15% of pork back-fat), and a quinoa low-fat (LF; 85% of fat replacement; 4.5% of pork back-fat) sausage. 27442806 6 71 theme replacement 856:866 arg1 replacement 856:866 fat replacement 852:866 fat replacement 852:866 Three types of sausages were prepared: a control (C; no fat replacement; 30% of pork back-fat), a quinoa half-fat (50% of fat replacement; 15% of pork back-fat), and a quinoa low-fat (LF; 85% of fat replacement; 4.5% of pork back-fat) sausage. 27442806 9 72 theme cohesiveness 1298:1309 arg1 < 1321:1321 P < 0.05 1319:1326 P < 0.05 1319:1326 Fat reduction resulted in higher aw , protein content, hardness, chewiness and redness values and spice-derived volatile levels, and in lower cohesiveness values (P < 0.05). 27442806 9 72 theme cohesiveness 1298:1309 arg1 values 1311:1316 lower cohesiveness values 1292:1316 lower cohesiveness values (P < 0.05) 1292:1327 Fat reduction resulted in higher aw , protein content, hardness, chewiness and redness values and spice-derived volatile levels, and in lower cohesiveness values (P < 0.05). 27442806 11 73 theme fat 1504:1506 arg1 reduction 1508:1516 fat reduction 1504:1516 fat reduction 1504:1516 In spite of those differences, fat reduction did not result in a decreased overall acceptance of the sausages by consumers. 27442806 0 74 theme Sausage 87:93 arg1 Characteristics 56:70 the Quality Characteristics 44:70 the Quality Characteristics of a Dry-Cured Sausage 44:93 Partial Fat Replacement by Boiled Quinoa on the Quality Characteristics of a Dry-Cured Sausage. 27442806 8 75 theme sensory 1118:1124 arg1 analyses 1126:1133 Descriptive and hedonic sensory analyses 1094:1133 Descriptive and hedonic sensory analyses 1094:1133 Descriptive and hedonic sensory analyses were also performed. 27442806 10 76 theme lower 1411:1415 arg1 juiciness 1417:1425 lower juiciness 1411:1425 lower juiciness in LF sausages 1411:1440 Furthermore, the descriptive sensory analysis showed a higher pungent flavor and lower juiciness in LF sausages than in C sausages (P < 0.05). 27442806 5 77 theme sausage 721:727 arg1 characteristics 675:689 the quality characteristics 663:689 the quality characteristics of a small diameter dry-cured sausage 663:727 The aim of this study was to assess the effect of replacing fat by quinoa on the quality characteristics of a small diameter dry-cured sausage. 27442806 6 78 theme back-fat 881:888 arg1 % 871:871 15% 869:871 50% of fat replacement; 15% of pork back-fat 845:888 Three types of sausages were prepared: a control (C; no fat replacement; 30% of pork back-fat), a quinoa half-fat (50% of fat replacement; 15% of pork back-fat), and a quinoa low-fat (LF; 85% of fat replacement; 4.5% of pork back-fat) sausage. 27442806 6 78 theme back-fat 881:888 arg1 back-fat 881:888 pork back-fat 876:888 pork back-fat 876:888 Three types of sausages were prepared: a control (C; no fat replacement; 30% of pork back-fat), a quinoa half-fat (50% of fat replacement; 15% of pork back-fat), and a quinoa low-fat (LF; 85% of fat replacement; 4.5% of pork back-fat) sausage. 27442806 6 79 dep prepared 759:766 arg1 control 771:777 a control 769:777 a control (C; no fat replacement; 30% of pork back-fat) 769:823 Three types of sausages were prepared: a control (C; no fat replacement; 30% of pork back-fat), a quinoa half-fat (50% of fat replacement; 15% of pork back-fat), and a quinoa low-fat (LF; 85% of fat replacement; 4.5% of pork back-fat) sausage. 27442806 6 79 dep prepared 759:766 arg1 sausage 965:971 a quinoa low-fat (LF; 85% of fat replacement; 4.5% of pork back-fat) sausage 896:971 a quinoa low-fat (LF; 85% of fat replacement; 4.5% of pork back-fat) sausage 896:971 Three types of sausages were prepared: a control (C; no fat replacement; 30% of pork back-fat), a quinoa half-fat (50% of fat replacement; 15% of pork back-fat), and a quinoa low-fat (LF; 85% of fat replacement; 4.5% of pork back-fat) sausage. 27442806 6 79 dep prepared 759:766 arg1 half-fat 835:842 a quinoa half-fat 826:842 a quinoa half-fat (50% of fat replacement; 15% of pork back-fat) 826:889 Three types of sausages were prepared: a control (C; no fat replacement; 30% of pork back-fat), a quinoa half-fat (50% of fat replacement; 15% of pork back-fat), and a quinoa low-fat (LF; 85% of fat replacement; 4.5% of pork back-fat) sausage. 27442806 7 80 theme instrumental 1062:1073 arg1 texture 1075:1081 texture 1075:1081 texture 1075:1081 Sausages were analyzed for proximate and microbial composition, volatile compounds, and instrumental texture and color. 27442806 5 81 theme diameter 702:709 arg1 sausage 721:727 a small diameter dry-cured sausage 694:727 a small diameter dry-cured sausage 694:727 The aim of this study was to assess the effect of replacing fat by quinoa on the quality characteristics of a small diameter dry-cured sausage. 27442806 11 82 theme overall 1548:1554 arg1 acceptance 1556:1565 a decreased overall acceptance 1536:1565 a decreased overall acceptance of the sausages by consumers 1536:1594 In spite of those differences, fat reduction did not result in a decreased overall acceptance of the sausages by consumers. 27442806 10 83 from flavor 1400:1405 arg1 sausages 1433:1440 LF sausages 1430:1440 LF sausages 1430:1440 Furthermore, the descriptive sensory analysis showed a higher pungent flavor and lower juiciness in LF sausages than in C sausages (P < 0.05). 27442806 2 84 theme replacing 303:311 arg1 fat 299:301 fat replacing 299:311 fat replacing 299:311 Among them, the use of polysaccharides, such as fiber, gums, or starch, have been proposed for fat replacing. 27442806 11 85 theme sausages 1574:1581 arg1 acceptance 1556:1565 a decreased overall acceptance 1536:1565 a decreased overall acceptance of the sausages by consumers 1536:1594 In spite of those differences, fat reduction did not result in a decreased overall acceptance of the sausages by consumers. 27442806 7 86 theme volatile 1038:1045 arg1 compounds 1047:1055 volatile compounds 1038:1055 volatile compounds 1038:1055 Sausages were analyzed for proximate and microbial composition, volatile compounds, and instrumental texture and color. 27442806 3 87 theme potential 411:419 arg1 vegetables 378:387 vegetables 378:387 vegetables 378:387 Although scarcely studied, it is likely that starchy grains and vegetables might also be used as potential fat replacers in those sausages. 27442806 3 87 theme potential 411:419 arg1 replacers 425:433 potential fat replacers 411:433 potential fat replacers in those sausages 411:451 Although scarcely studied, it is likely that starchy grains and vegetables might also be used as potential fat replacers in those sausages. 27442806 3 87 theme potential 411:419 arg1 grains 367:372 starchy grains 359:372 starchy grains 359:372 Although scarcely studied, it is likely that starchy grains and vegetables might also be used as potential fat replacers in those sausages. 27442806 4 88 theme interest 549:556 arg1 substances 521:530 substances 521:530 substances of technological interest in dry-cured manufacturing 521:583 Quinua is a starchy seed with high nutritive value, which contains substances of technological interest in dry-cured manufacturing. 27442806 0 89 theme Fat 8:10 arg1 Replacement 12:22 Partial Fat Replacement 0:22 Partial Fat Replacement by Boiled Quinoa on the Quality Characteristics of a Dry-Cured Sausage 0:93 Partial Fat Replacement by Boiled Quinoa on the Quality Characteristics of a Dry-Cured Sausage. 27442806 9 90 theme aw 1189:1190 arg1 values 1243:1248 aw , protein content, hardness, chewiness and redness values 1189:1248 aw , protein content, hardness, chewiness and redness values 1189:1248 Fat reduction resulted in higher aw , protein content, hardness, chewiness and redness values and spice-derived volatile levels, and in lower cohesiveness values (P < 0.05). 26101572 0 0 theme Receptor 77:84 arg1 Antagonists 86:96 Brain Penetrant P2X7 Receptor Antagonists 56:96 Brain Penetrant P2X7 Receptor Antagonists 56:96 Synthesis, SAR, and Pharmacological Characterization of Brain Penetrant P2X7 Receptor Antagonists. 26101572 3 1 theme N-linked 458:465 arg1 heterocycle 467:477 the N-linked heterocycle 454:477 the N-linked heterocycle 454:477 Further work in this series, which focused on the SAR of the N-linked heterocycle, not only increased the potency at the human P2X7R but also provided compounds with good potency at the rat P2X7R. 26101572 4 2 theme pharmacokinetic 720:734 arg1 partitioning 750:761 good partitioning 745:761 good partitioning into the CNS 745:774 These efforts eventually delivered a potent rat and human P2X7R antagonist with good physicochemical properties, an excellent pharmacokinetic profile, good partitioning into the CNS, and demonstrated in vivo target engagement after oral dosing. 26101572 4 2 theme pharmacokinetic 720:734 arg1 properties 695:704 good physicochemical properties 674:704 good physicochemical properties 674:704 These efforts eventually delivered a potent rat and human P2X7R antagonist with good physicochemical properties, an excellent pharmacokinetic profile, good partitioning into the CNS, and demonstrated in vivo target engagement after oral dosing. 26101572 4 2 theme pharmacokinetic 720:734 arg1 profile 736:742 an excellent pharmacokinetic profile 707:742 an excellent pharmacokinetic profile 707:742 These efforts eventually delivered a potent rat and human P2X7R antagonist with good physicochemical properties, an excellent pharmacokinetic profile, good partitioning into the CNS, and demonstrated in vivo target engagement after oral dosing. 26101572 0 3 theme P2X7 72:75 arg1 Antagonists 86:96 Brain Penetrant P2X7 Receptor Antagonists 56:96 Brain Penetrant P2X7 Receptor Antagonists 56:96 Synthesis, SAR, and Pharmacological Characterization of Brain Penetrant P2X7 Receptor Antagonists. 26101572 2 4 theme CYP 335:337 arg1 inhibition 339:348 some CYP inhibition 330:348 some CYP inhibition 330:348 Initial efforts yielded a series of potent human P2X7R antagonists with moderate to weak rodent potency, some CYP inhibition, poor metabolic stability, and low solubility. 26101572 2 5 theme antagonists 280:290 arg1 series 251:256 a series 249:256 a series of potent human P2X7R antagonists 249:290 Initial efforts yielded a series of potent human P2X7R antagonists with moderate to weak rodent potency, some CYP inhibition, poor metabolic stability, and low solubility. 26101572 0 6 theme Antagonists 86:96 arg1 SAR 11:13 SAR 11:13 SAR 11:13 Synthesis, SAR, and Pharmacological Characterization of Brain Penetrant P2X7 Receptor Antagonists. 26101572 0 6 theme Antagonists 86:96 arg1 Synthesis 0:8 Synthesis 0:8 Synthesis 0:8 Synthesis, SAR, and Pharmacological Characterization of Brain Penetrant P2X7 Receptor Antagonists. 26101572 0 6 theme Antagonists 86:96 arg1 Characterization 36:51 Pharmacological Characterization 20:51 Pharmacological Characterization 20:51 Synthesis, SAR, and Pharmacological Characterization of Brain Penetrant P2X7 Receptor Antagonists. 26101572 4 7 theme oral 826:829 arg1 dosing 831:836 oral dosing 826:836 oral dosing 826:836 These efforts eventually delivered a potent rat and human P2X7R antagonist with good physicochemical properties, an excellent pharmacokinetic profile, good partitioning into the CNS, and demonstrated in vivo target engagement after oral dosing. 26101572 2 8 theme P2X7R 274:278 arg1 antagonists 280:290 potent human P2X7R antagonists 261:290 potent human P2X7R antagonists 261:290 Initial efforts yielded a series of potent human P2X7R antagonists with moderate to weak rodent potency, some CYP inhibition, poor metabolic stability, and low solubility. 26101572 4 9 theme in 794:795 arg1 engagement 809:818 in vivo target engagement 794:818 in vivo target engagement 794:818 These efforts eventually delivered a potent rat and human P2X7R antagonist with good physicochemical properties, an excellent pharmacokinetic profile, good partitioning into the CNS, and demonstrated in vivo target engagement after oral dosing. 26101572 4 10 theme physicochemical 679:693 arg1 properties 695:704 good physicochemical properties 674:704 good physicochemical properties 674:704 These efforts eventually delivered a potent rat and human P2X7R antagonist with good physicochemical properties, an excellent pharmacokinetic profile, good partitioning into the CNS, and demonstrated in vivo target engagement after oral dosing. 26101572 4 10 theme physicochemical 679:693 arg1 profile 736:742 an excellent pharmacokinetic profile 707:742 an excellent pharmacokinetic profile 707:742 These efforts eventually delivered a potent rat and human P2X7R antagonist with good physicochemical properties, an excellent pharmacokinetic profile, good partitioning into the CNS, and demonstrated in vivo target engagement after oral dosing. 26101572 2 11 theme human 268:272 arg1 antagonists 280:290 potent human P2X7R antagonists 261:290 potent human P2X7R antagonists 261:290 Initial efforts yielded a series of potent human P2X7R antagonists with moderate to weak rodent potency, some CYP inhibition, poor metabolic stability, and low solubility. 26101572 1 12 theme novel 167:171 arg1 SAR 129:131 SAR 129:131 SAR 129:131 We describe the synthesis and SAR of 1,2,3-triazolopiperidines as a novel series of potent, brain penetrant P2X7 antagonists. 26101572 1 12 theme novel 167:171 arg1 series 173:178 a novel series 165:178 a novel series of potent, brain penetrant P2X7 antagonists 165:222 We describe the synthesis and SAR of 1,2,3-triazolopiperidines as a novel series of potent, brain penetrant P2X7 antagonists. 26101572 1 12 theme novel 167:171 arg1 synthesis 115:123 synthesis 115:123 synthesis 115:123 We describe the synthesis and SAR of 1,2,3-triazolopiperidines as a novel series of potent, brain penetrant P2X7 antagonists. 26101572 3 13 with compounds 548:556 arg1 potency 568:574 good potency 563:574 good potency 563:574 Further work in this series, which focused on the SAR of the N-linked heterocycle, not only increased the potency at the human P2X7R but also provided compounds with good potency at the rat P2X7R. 26101572 2 14 theme potent 261:266 arg1 antagonists 280:290 potent human P2X7R antagonists 261:290 potent human P2X7R antagonists 261:290 Initial efforts yielded a series of potent human P2X7R antagonists with moderate to weak rodent potency, some CYP inhibition, poor metabolic stability, and low solubility. 26101572 4 15 theme target 802:807 arg1 engagement 809:818 in vivo target engagement 794:818 in vivo target engagement 794:818 These efforts eventually delivered a potent rat and human P2X7R antagonist with good physicochemical properties, an excellent pharmacokinetic profile, good partitioning into the CNS, and demonstrated in vivo target engagement after oral dosing. 26101572 2 16 theme weak 309:312 arg1 potency 321:327 moderate to weak rodent potency 297:327 moderate to weak rodent potency 297:327 Initial efforts yielded a series of potent human P2X7R antagonists with moderate to weak rodent potency, some CYP inhibition, poor metabolic stability, and low solubility. 26101572 4 17 theme good 674:677 arg1 properties 695:704 good physicochemical properties 674:704 good physicochemical properties 674:704 These efforts eventually delivered a potent rat and human P2X7R antagonist with good physicochemical properties, an excellent pharmacokinetic profile, good partitioning into the CNS, and demonstrated in vivo target engagement after oral dosing. 26101572 4 17 theme good 674:677 arg1 profile 736:742 an excellent pharmacokinetic profile 707:742 an excellent pharmacokinetic profile 707:742 These efforts eventually delivered a potent rat and human P2X7R antagonist with good physicochemical properties, an excellent pharmacokinetic profile, good partitioning into the CNS, and demonstrated in vivo target engagement after oral dosing. 26101572 2 18 theme metabolic 356:364 arg1 stability 366:374 poor metabolic stability 351:374 poor metabolic stability 351:374 Initial efforts yielded a series of potent human P2X7R antagonists with moderate to weak rodent potency, some CYP inhibition, poor metabolic stability, and low solubility. 26101572 4 19 dep in 794:795 arg1 vivo 797:800 vivo 797:800 vivo 797:800 These efforts eventually delivered a potent rat and human P2X7R antagonist with good physicochemical properties, an excellent pharmacokinetic profile, good partitioning into the CNS, and demonstrated in vivo target engagement after oral dosing. 26101572 3 20 link N-linked 458:465 arg1 heterocycle 467:477 the N-linked heterocycle 454:477 the N-linked heterocycle 454:477 Further work in this series, which focused on the SAR of the N-linked heterocycle, not only increased the potency at the human P2X7R but also provided compounds with good potency at the rat P2X7R. 26101572 3 21 theme heterocycle 467:477 arg1 SAR 447:449 the SAR 443:449 the SAR of the N-linked heterocycle 443:477 Further work in this series, which focused on the SAR of the N-linked heterocycle, not only increased the potency at the human P2X7R but also provided compounds with good potency at the rat P2X7R. 26101572 4 22 theme potent 631:636 arg1 rat 638:640 a potent rat and human P2X7R antagonist 629:667 rat 638:640 These efforts eventually delivered a potent rat and human P2X7R antagonist with good physicochemical properties, an excellent pharmacokinetic profile, good partitioning into the CNS, and demonstrated in vivo target engagement after oral dosing. 26101572 0 23 theme Pharmacological 20:34 arg1 Characterization 36:51 Pharmacological Characterization 20:51 Pharmacological Characterization 20:51 Synthesis, SAR, and Pharmacological Characterization of Brain Penetrant P2X7 Receptor Antagonists. 26101572 1 24 theme potent 183:188 arg1 antagonists 212:222 potent, brain penetrant P2X7 antagonists 183:222 potent, brain penetrant P2X7 antagonists 183:222 We describe the synthesis and SAR of 1,2,3-triazolopiperidines as a novel series of potent, brain penetrant P2X7 antagonists. 26101572 3 25 theme Further 397:403 arg1 work 405:408 Further work 397:408 Further work 397:408 Further work in this series, which focused on the SAR of the N-linked heterocycle, not only increased the potency at the human P2X7R but also provided compounds with good potency at the rat P2X7R. 26101572 1 26 dep potent 183:188 arg1 penetrant 197:205 penetrant 197:205 penetrant 197:205 We describe the synthesis and SAR of 1,2,3-triazolopiperidines as a novel series of potent, brain penetrant P2X7 antagonists. 26101572 1 27 theme P2X7 207:210 arg1 antagonists 212:222 potent, brain penetrant P2X7 antagonists 183:222 potent, brain penetrant P2X7 antagonists 183:222 We describe the synthesis and SAR of 1,2,3-triazolopiperidines as a novel series of potent, brain penetrant P2X7 antagonists. 26101572 3 28 theme rat 583:585 arg1 P2X7R 587:591 the rat P2X7R 579:591 the rat P2X7R 579:591 Further work in this series, which focused on the SAR of the N-linked heterocycle, not only increased the potency at the human P2X7R but also provided compounds with good potency at the rat P2X7R. 26101572 4 29 theme P2X7R 652:656 arg1 antagonist 658:667 a potent rat and human P2X7R antagonist 629:667 antagonist 658:667 These efforts eventually delivered a potent rat and human P2X7R antagonist with good physicochemical properties, an excellent pharmacokinetic profile, good partitioning into the CNS, and demonstrated in vivo target engagement after oral dosing. 26101572 4 30 theme human 646:650 arg1 antagonist 658:667 a potent rat and human P2X7R antagonist 629:667 antagonist 658:667 These efforts eventually delivered a potent rat and human P2X7R antagonist with good physicochemical properties, an excellent pharmacokinetic profile, good partitioning into the CNS, and demonstrated in vivo target engagement after oral dosing. 26101572 3 31 theme human 518:522 arg1 P2X7R 524:528 the human P2X7R 514:528 the human P2X7R 514:528 Further work in this series, which focused on the SAR of the N-linked heterocycle, not only increased the potency at the human P2X7R but also provided compounds with good potency at the rat P2X7R. 26101572 4 32 theme good 745:748 arg1 partitioning 750:761 good partitioning 745:761 good partitioning into the CNS 745:774 These efforts eventually delivered a potent rat and human P2X7R antagonist with good physicochemical properties, an excellent pharmacokinetic profile, good partitioning into the CNS, and demonstrated in vivo target engagement after oral dosing. 26101572 4 32 theme good 745:748 arg1 profile 736:742 an excellent pharmacokinetic profile 707:742 an excellent pharmacokinetic profile 707:742 These efforts eventually delivered a potent rat and human P2X7R antagonist with good physicochemical properties, an excellent pharmacokinetic profile, good partitioning into the CNS, and demonstrated in vivo target engagement after oral dosing. 26101572 2 33 theme Initial 225:231 arg1 efforts 233:239 Initial efforts 225:239 Initial efforts 225:239 Initial efforts yielded a series of potent human P2X7R antagonists with moderate to weak rodent potency, some CYP inhibition, poor metabolic stability, and low solubility. 26101572 2 34 dep weak 309:312 arg1 to 306:307 to 306:307 to 306:307 Initial efforts yielded a series of potent human P2X7R antagonists with moderate to weak rodent potency, some CYP inhibition, poor metabolic stability, and low solubility. 26101572 1 35 theme antagonists 212:222 arg1 SAR 129:131 SAR 129:131 SAR 129:131 We describe the synthesis and SAR of 1,2,3-triazolopiperidines as a novel series of potent, brain penetrant P2X7 antagonists. 26101572 1 35 theme antagonists 212:222 arg1 series 173:178 a novel series 165:178 a novel series of potent, brain penetrant P2X7 antagonists 165:222 We describe the synthesis and SAR of 1,2,3-triazolopiperidines as a novel series of potent, brain penetrant P2X7 antagonists. 26101572 1 35 theme antagonists 212:222 arg1 synthesis 115:123 synthesis 115:123 synthesis 115:123 We describe the synthesis and SAR of 1,2,3-triazolopiperidines as a novel series of potent, brain penetrant P2X7 antagonists. 26101572 1 36 dep synthesis 115:123 arg1 the 111:113 the 111:113 the 111:113 We describe the synthesis and SAR of 1,2,3-triazolopiperidines as a novel series of potent, brain penetrant P2X7 antagonists. 26101572 4 37 theme excellent 710:718 arg1 partitioning 750:761 good partitioning 745:761 good partitioning into the CNS 745:774 These efforts eventually delivered a potent rat and human P2X7R antagonist with good physicochemical properties, an excellent pharmacokinetic profile, good partitioning into the CNS, and demonstrated in vivo target engagement after oral dosing. 26101572 4 37 theme excellent 710:718 arg1 properties 695:704 good physicochemical properties 674:704 good physicochemical properties 674:704 These efforts eventually delivered a potent rat and human P2X7R antagonist with good physicochemical properties, an excellent pharmacokinetic profile, good partitioning into the CNS, and demonstrated in vivo target engagement after oral dosing. 26101572 4 37 theme excellent 710:718 arg1 profile 736:742 an excellent pharmacokinetic profile 707:742 an excellent pharmacokinetic profile 707:742 These efforts eventually delivered a potent rat and human P2X7R antagonist with good physicochemical properties, an excellent pharmacokinetic profile, good partitioning into the CNS, and demonstrated in vivo target engagement after oral dosing. 26101572 3 38 from work 405:408 arg1 series 418:423 this series 413:423 this series 413:423 Further work in this series, which focused on the SAR of the N-linked heterocycle, not only increased the potency at the human P2X7R but also provided compounds with good potency at the rat P2X7R. 26101572 2 39 theme rodent 314:319 arg1 potency 321:327 moderate to weak rodent potency 297:327 moderate to weak rodent potency 297:327 Initial efforts yielded a series of potent human P2X7R antagonists with moderate to weak rodent potency, some CYP inhibition, poor metabolic stability, and low solubility. 26101572 0 40 theme Penetrant 62:70 arg1 Antagonists 86:96 Brain Penetrant P2X7 Receptor Antagonists 56:96 Brain Penetrant P2X7 Receptor Antagonists 56:96 Synthesis, SAR, and Pharmacological Characterization of Brain Penetrant P2X7 Receptor Antagonists. 26101572 2 41 theme low 381:383 arg1 solubility 385:394 low solubility 381:394 low solubility 381:394 Initial efforts yielded a series of potent human P2X7R antagonists with moderate to weak rodent potency, some CYP inhibition, poor metabolic stability, and low solubility. 26101572 2 42 theme poor 351:354 arg1 stability 366:374 poor metabolic stability 351:374 poor metabolic stability 351:374 Initial efforts yielded a series of potent human P2X7R antagonists with moderate to weak rodent potency, some CYP inhibition, poor metabolic stability, and low solubility. 26101572 0 43 theme Brain 56:60 arg1 Antagonists 86:96 Brain Penetrant P2X7 Receptor Antagonists 56:96 Brain Penetrant P2X7 Receptor Antagonists 56:96 Synthesis, SAR, and Pharmacological Characterization of Brain Penetrant P2X7 Receptor Antagonists. 26101572 3 44 theme good 563:566 arg1 potency 568:574 good potency 563:574 good potency 563:574 Further work in this series, which focused on the SAR of the N-linked heterocycle, not only increased the potency at the human P2X7R but also provided compounds with good potency at the rat P2X7R. 26101572 1 45 theme 1,2,3-triazolopiperidines 136:160 arg1 SAR 129:131 SAR 129:131 SAR 129:131 We describe the synthesis and SAR of 1,2,3-triazolopiperidines as a novel series of potent, brain penetrant P2X7 antagonists. 26101572 1 45 theme 1,2,3-triazolopiperidines 136:160 arg1 synthesis 115:123 synthesis 115:123 synthesis 115:123 We describe the synthesis and SAR of 1,2,3-triazolopiperidines as a novel series of potent, brain penetrant P2X7 antagonists. 26101572 1 45 theme 1,2,3-triazolopiperidines 136:160 arg1 series 173:178 a novel series 165:178 a novel series of potent, brain penetrant P2X7 antagonists 165:222 We describe the synthesis and SAR of 1,2,3-triazolopiperidines as a novel series of potent, brain penetrant P2X7 antagonists. 25408454 2 0 from process 171:177 arg1 reticulum 198:206 the endoplasmic reticulum 182:206 the endoplasmic reticulum 182:206 It is initiated by a conserved process in the endoplasmic reticulum and subsequently involves a series of different N-glycan maturation steps that take place in the ER and Golgi apparatus. 25408454 3 1 attach present 466:472 arg2 glycoforms 455:464 characteristic glycoforms 440:464 characteristic glycoforms present on individual plant glycoproteins 440:506 Despite our vast knowledge on the different processing steps we still understand very little about the role of characteristic glycoforms present on individual plant glycoproteins. 25408454 3 1 attach present 466:472 arg1 glycoproteins 494:506 individual plant glycoproteins 477:506 individual plant glycoproteins 477:506 Despite our vast knowledge on the different processing steps we still understand very little about the role of characteristic glycoforms present on individual plant glycoproteins. 25408454 4 2 theme reliable 568:575 arg1 characterization 577:592 the fast and reliable characterization 555:592 the fast and reliable characterization of N-glycosylation on plant glycoproteins 555:634 Here, we describe convenient tools that allow the fast and reliable characterization of N-glycosylation on plant glycoproteins. 25408454 5 3 gly glycoproteins 755:767 arg1 glycoproteins 755:767 different glycoproteins 745:767 different glycoproteins 745:767 The presented protocols can be adopted to other plant species and to the characterization of N-glycans from different glycoproteins. 25408454 4 4 theme N-glycosylation 597:611 arg1 characterization 577:592 the fast and reliable characterization 555:592 the fast and reliable characterization of N-glycosylation on plant glycoproteins 555:634 Here, we describe convenient tools that allow the fast and reliable characterization of N-glycosylation on plant glycoproteins. 25408454 5 5 theme different 745:753 arg1 glycoproteins 755:767 different glycoproteins 745:767 different glycoproteins 745:767 The presented protocols can be adopted to other plant species and to the characterization of N-glycans from different glycoproteins. 25408454 5 6 theme other 679:683 arg1 species 691:697 other plant species 679:697 other plant species 679:697 The presented protocols can be adopted to other plant species and to the characterization of N-glycans from different glycoproteins. 25408454 4 7 gly glycoproteins 622:634 arg1 glycoproteins 622:634 plant glycoproteins 616:634 plant glycoproteins 616:634 Here, we describe convenient tools that allow the fast and reliable characterization of N-glycosylation on plant glycoproteins. 25408454 2 8 dep ER 305:306 arg1 the 301:303 the 301:303 the 301:303 It is initiated by a conserved process in the endoplasmic reticulum and subsequently involves a series of different N-glycan maturation steps that take place in the ER and Golgi apparatus. 25408454 4 9 from characterization 577:592 arg1 glycoproteins 622:634 plant glycoproteins 616:634 plant glycoproteins 616:634 Here, we describe convenient tools that allow the fast and reliable characterization of N-glycosylation on plant glycoproteins. 25408454 1 10 theme modifications 115:127 arg1 modifications 115:127 the most prevalent cotranslational protein modifications 72:127 the most prevalent cotranslational protein modifications in plants 72:137 N-linked glycosylation is one of the most prevalent cotranslational protein modifications in plants. 25408454 1 10 theme modifications 115:127 arg1 one 65:67 one 65:67 one 65:67 N-linked glycosylation is one of the most prevalent cotranslational protein modifications in plants. 25408454 5 11 from characterization 710:725 arg1 glycoproteins 755:767 different glycoproteins 745:767 different glycoproteins 745:767 The presented protocols can be adopted to other plant species and to the characterization of N-glycans from different glycoproteins. 25408454 3 12 theme vast 341:344 arg1 knowledge 346:354 our vast knowledge 337:354 our vast knowledge on the different processing steps 337:388 Despite our vast knowledge on the different processing steps we still understand very little about the role of characteristic glycoforms present on individual plant glycoproteins. 25408454 5 13 theme presented 641:649 arg1 protocols 651:659 The presented protocols 637:659 The presented protocols 637:659 The presented protocols can be adopted to other plant species and to the characterization of N-glycans from different glycoproteins. 25408454 2 14 theme steps 276:280 arg1 series 236:241 a series 234:241 a series of different N-glycan maturation steps that take place in the ER and Golgi apparatus 234:326 It is initiated by a conserved process in the endoplasmic reticulum and subsequently involves a series of different N-glycan maturation steps that take place in the ER and Golgi apparatus. 25408454 1 15 link N-linked 39:46 arg1 glycosylation 48:60 N-linked glycosylation 39:60 N-linked glycosylation 39:60 N-linked glycosylation is one of the most prevalent cotranslational protein modifications in plants. 25408454 3 16 gly glycoproteins 494:506 arg1 glycoproteins 494:506 individual plant glycoproteins 477:506 individual plant glycoproteins 477:506 Despite our vast knowledge on the different processing steps we still understand very little about the role of characteristic glycoforms present on individual plant glycoproteins. 25408454 1 17 from modifications 115:127 arg1 plants 132:137 plants 132:137 plants 132:137 N-linked glycosylation is one of the most prevalent cotranslational protein modifications in plants. 25408454 1 18 theme prevalent 81:89 arg1 modifications 115:127 the most prevalent cotranslational protein modifications 72:127 the most prevalent cotranslational protein modifications in plants 72:137 N-linked glycosylation is one of the most prevalent cotranslational protein modifications in plants. 25408454 0 19 theme cell 26:29 arg1 growth 31:36 plant cell growth 20:36 plant cell growth 20:36 N-Glycosylation and plant cell growth. 25408454 1 20 theme N-linked 39:46 arg1 glycosylation 48:60 N-linked glycosylation 39:60 N-linked glycosylation 39:60 N-linked glycosylation is one of the most prevalent cotranslational protein modifications in plants. 25408454 1 21 theme cotranslational 91:105 arg1 modifications 115:127 the most prevalent cotranslational protein modifications 72:127 the most prevalent cotranslational protein modifications in plants 72:137 N-linked glycosylation is one of the most prevalent cotranslational protein modifications in plants. 25408454 3 22 theme glycoforms 455:464 arg1 role 432:435 the role 428:435 the role of characteristic glycoforms present on individual plant glycoproteins 428:506 Despite our vast knowledge on the different processing steps we still understand very little about the role of characteristic glycoforms present on individual plant glycoproteins. 25408454 0 23 theme plant 20:24 arg1 growth 31:36 plant cell growth 20:36 plant cell growth 20:36 N-Glycosylation and plant cell growth. 25408454 5 24 from glycoproteins 755:767 arg1 characterization 710:725 the characterization 706:725 the characterization of N-glycans from different glycoproteins 706:767 The presented protocols can be adopted to other plant species and to the characterization of N-glycans from different glycoproteins. 25408454 5 24 from glycoproteins 755:767 arg1 N-glycans 730:738 N-glycans 730:738 N-glycans from different glycoproteins 730:767 The presented protocols can be adopted to other plant species and to the characterization of N-glycans from different glycoproteins. 25408454 1 25 theme protein 107:113 arg1 modifications 115:127 the most prevalent cotranslational protein modifications 72:127 the most prevalent cotranslational protein modifications in plants 72:137 N-linked glycosylation is one of the most prevalent cotranslational protein modifications in plants. 25408454 3 26 theme present 466:472 arg1 glycoforms 455:464 characteristic glycoforms 440:464 characteristic glycoforms present on individual plant glycoproteins 440:506 Despite our vast knowledge on the different processing steps we still understand very little about the role of characteristic glycoforms present on individual plant glycoproteins. 25408454 4 27 theme fast 559:562 arg1 characterization 577:592 the fast and reliable characterization 555:592 the fast and reliable characterization of N-glycosylation on plant glycoproteins 555:634 Here, we describe convenient tools that allow the fast and reliable characterization of N-glycosylation on plant glycoproteins. 25408454 4 28 theme convenient 527:536 arg1 tools 538:542 convenient tools 527:542 convenient tools that allow the fast and reliable characterization of N-glycosylation on plant glycoproteins 527:634 Here, we describe convenient tools that allow the fast and reliable characterization of N-glycosylation on plant glycoproteins. 25408454 5 29 theme N-glycans 730:738 arg1 characterization 710:725 the characterization 706:725 the characterization of N-glycans from different glycoproteins 706:767 The presented protocols can be adopted to other plant species and to the characterization of N-glycans from different glycoproteins. 25408454 2 30 theme conserved 161:169 arg1 process 171:177 a conserved process 159:177 a conserved process in the endoplasmic reticulum 159:206 It is initiated by a conserved process in the endoplasmic reticulum and subsequently involves a series of different N-glycan maturation steps that take place in the ER and Golgi apparatus. 25408454 3 31 theme characteristic 440:453 arg1 glycoforms 455:464 characteristic glycoforms 440:464 characteristic glycoforms present on individual plant glycoproteins 440:506 Despite our vast knowledge on the different processing steps we still understand very little about the role of characteristic glycoforms present on individual plant glycoproteins. 25408454 5 32 theme plant 685:689 arg1 species 691:697 other plant species 679:697 other plant species 679:697 The presented protocols can be adopted to other plant species and to the characterization of N-glycans from different glycoproteins. 25408454 3 33 theme plant 488:492 arg1 glycoproteins 494:506 individual plant glycoproteins 477:506 individual plant glycoproteins 477:506 Despite our vast knowledge on the different processing steps we still understand very little about the role of characteristic glycoforms present on individual plant glycoproteins. 25408454 3 34 from knowledge 346:354 arg1 steps 384:388 the different processing steps 359:388 the different processing steps 359:388 Despite our vast knowledge on the different processing steps we still understand very little about the role of characteristic glycoforms present on individual plant glycoproteins. 25408454 2 35 theme maturation 265:274 arg1 steps 276:280 different N-glycan maturation steps 246:280 different N-glycan maturation steps that take place in the ER and Golgi apparatus 246:326 It is initiated by a conserved process in the endoplasmic reticulum and subsequently involves a series of different N-glycan maturation steps that take place in the ER and Golgi apparatus. 25408454 4 36 theme plant 616:620 arg1 glycoproteins 622:634 plant glycoproteins 616:634 plant glycoproteins 616:634 Here, we describe convenient tools that allow the fast and reliable characterization of N-glycosylation on plant glycoproteins. 25408454 2 37 theme endoplasmic 186:196 arg1 reticulum 198:206 the endoplasmic reticulum 182:206 the endoplasmic reticulum 182:206 It is initiated by a conserved process in the endoplasmic reticulum and subsequently involves a series of different N-glycan maturation steps that take place in the ER and Golgi apparatus. 25408454 2 38 theme N-glycan 256:263 arg1 steps 276:280 different N-glycan maturation steps 246:280 different N-glycan maturation steps that take place in the ER and Golgi apparatus 246:326 It is initiated by a conserved process in the endoplasmic reticulum and subsequently involves a series of different N-glycan maturation steps that take place in the ER and Golgi apparatus. 25408454 2 39 theme Golgi 312:316 arg1 apparatus 318:326 Golgi apparatus 312:326 Golgi apparatus 312:326 It is initiated by a conserved process in the endoplasmic reticulum and subsequently involves a series of different N-glycan maturation steps that take place in the ER and Golgi apparatus. 25408454 2 40 theme different 246:254 arg1 steps 276:280 different N-glycan maturation steps 246:280 different N-glycan maturation steps that take place in the ER and Golgi apparatus 246:326 It is initiated by a conserved process in the endoplasmic reticulum and subsequently involves a series of different N-glycan maturation steps that take place in the ER and Golgi apparatus. 25408454 3 41 theme individual 477:486 arg1 glycoproteins 494:506 individual plant glycoproteins 477:506 individual plant glycoproteins 477:506 Despite our vast knowledge on the different processing steps we still understand very little about the role of characteristic glycoforms present on individual plant glycoproteins. 25408454 3 42 theme different 363:371 arg1 steps 384:388 the different processing steps 359:388 the different processing steps 359:388 Despite our vast knowledge on the different processing steps we still understand very little about the role of characteristic glycoforms present on individual plant glycoproteins. 25408454 3 43 theme processing 373:382 arg1 steps 384:388 the different processing steps 359:388 the different processing steps 359:388 Despite our vast knowledge on the different processing steps we still understand very little about the role of characteristic glycoforms present on individual plant glycoproteins. 25162384 1 0 dep S.-W. 298:302 arg1 R. 323:324 R. 323:324 R. 323:324 Evidence will be presented that in the article "Novel LC-MS(2) Product Dependent Parallel Data Acquisition Function and Data Analysis Workflow for Sequencing and Identification of Intact Glycopeptides" written by Wu, S.-W.; Pu, T.-H.; Viner, R.; Khoo, K.-H. 25162384 1 0 dep S.-W. 298:302 arg1 T.-H. 309:313 T.-H. 309:313 T.-H. 309:313 Evidence will be presented that in the article "Novel LC-MS(2) Product Dependent Parallel Data Acquisition Function and Data Analysis Workflow for Sequencing and Identification of Intact Glycopeptides" written by Wu, S.-W.; Pu, T.-H.; Viner, R.; Khoo, K.-H. 25162384 1 0 dep S.-W. 298:302 arg1 Khoo 327:330 Khoo 327:330 Khoo 327:330 Evidence will be presented that in the article "Novel LC-MS(2) Product Dependent Parallel Data Acquisition Function and Data Analysis Workflow for Sequencing and Identification of Intact Glycopeptides" written by Wu, S.-W.; Pu, T.-H.; Viner, R.; Khoo, K.-H. 25162384 4 1 theme well-defined 455:466 arg1 structures 477:486 well-defined N-linked structures 455:486 well-defined N-linked structures 455:486 2014, 86, 5478-5486, noncovalent homo- and heterodimers were mis-identified as glycopeptides bearing well-defined N-linked structures, where the unexplained mass was attributed to excessive O-glycosylation. 25162384 5 2 theme Noncovalent 561:571 arg1 complication 652:663 a complication 650:663 a complication in high-throughput proteomic analyses 650:701 Noncovalent dimer formation of abundant components has not previously been considered as a complication in high-throughput proteomic analyses. 25162384 5 2 theme Noncovalent 561:571 arg1 formation 579:587 Noncovalent dimer formation 561:587 Noncovalent dimer formation of abundant components 561:610 Noncovalent dimer formation of abundant components has not previously been considered as a complication in high-throughput proteomic analyses. 25162384 1 3 theme Intact 261:266 arg1 Glycopeptides 268:280 Intact Glycopeptides 261:280 Intact Glycopeptides" written by Wu, S.-W.; Pu, T.-H.; Viner, R.; Khoo 261:330 Evidence will be presented that in the article "Novel LC-MS(2) Product Dependent Parallel Data Acquisition Function and Data Analysis Workflow for Sequencing and Identification of Intact Glycopeptides" written by Wu, S.-W.; Pu, T.-H.; Viner, R.; Khoo, K.-H. 25162384 5 4 theme dimer 573:577 arg1 complication 652:663 a complication 650:663 a complication in high-throughput proteomic analyses 650:701 Noncovalent dimer formation of abundant components has not previously been considered as a complication in high-throughput proteomic analyses. 25162384 5 4 theme dimer 573:577 arg1 formation 579:587 Noncovalent dimer formation 561:587 Noncovalent dimer formation of abundant components 561:610 Noncovalent dimer formation of abundant components has not previously been considered as a complication in high-throughput proteomic analyses. 25162384 1 5 theme Glycopeptides 268:280 arg1 Sequencing 228:237 Sequencing 228:237 Sequencing 228:237 Evidence will be presented that in the article "Novel LC-MS(2) Product Dependent Parallel Data Acquisition Function and Data Analysis Workflow for Sequencing and Identification of Intact Glycopeptides" written by Wu, S.-W.; Pu, T.-H.; Viner, R.; Khoo, K.-H. 25162384 1 5 theme Glycopeptides 268:280 arg1 K.-H 333:336 K.-H 333:336 K.-H 333:336 Evidence will be presented that in the article "Novel LC-MS(2) Product Dependent Parallel Data Acquisition Function and Data Analysis Workflow for Sequencing and Identification of Intact Glycopeptides" written by Wu, S.-W.; Pu, T.-H.; Viner, R.; Khoo, K.-H. 25162384 1 5 theme Glycopeptides 268:280 arg1 Identification 243:256 Identification 243:256 Identification 243:256 Evidence will be presented that in the article "Novel LC-MS(2) Product Dependent Parallel Data Acquisition Function and Data Analysis Workflow for Sequencing and Identification of Intact Glycopeptides" written by Wu, S.-W.; Pu, T.-H.; Viner, R.; Khoo, K.-H. 25162384 4 6 gly glycopeptides 433:445 arg2 2014 354:357 2014 354:357 2014 354:357 2014, 86, 5478-5486, noncovalent homo- and heterodimers were mis-identified as glycopeptides bearing well-defined N-linked structures, where the unexplained mass was attributed to excessive O-glycosylation. 25162384 4 6 gly glycopeptides 433:445 arg2 glycopeptides 433:445 glycopeptides 433:445 glycopeptides 433:445 2014, 86, 5478-5486, noncovalent homo- and heterodimers were mis-identified as glycopeptides bearing well-defined N-linked structures, where the unexplained mass was attributed to excessive O-glycosylation. 25162384 4 7 theme excessive 534:542 arg1 O-glycosylation 544:558 excessive O-glycosylation 534:558 excessive O-glycosylation 534:558 2014, 86, 5478-5486, noncovalent homo- and heterodimers were mis-identified as glycopeptides bearing well-defined N-linked structures, where the unexplained mass was attributed to excessive O-glycosylation. 25162384 5 8 theme abundant 592:599 arg1 components 601:610 abundant components 592:610 abundant components 592:610 Noncovalent dimer formation of abundant components has not previously been considered as a complication in high-throughput proteomic analyses. 25162384 1 9 theme Parallel 162:169 arg1 Function 188:195 Parallel Data Acquisition Function 162:195 Parallel Data Acquisition Function 162:195 Evidence will be presented that in the article "Novel LC-MS(2) Product Dependent Parallel Data Acquisition Function and Data Analysis Workflow for Sequencing and Identification of Intact Glycopeptides" written by Wu, S.-W.; Pu, T.-H.; Viner, R.; Khoo, K.-H. 25162384 0 10 theme dimer 12:16 arg1 formation 18:26 Noncovalent dimer formation 0:26 Noncovalent dimer formation 0:26 Noncovalent dimer formation in liquid chromatography-mass spectrometry analysis. 25162384 4 11 link N-linked 468:475 arg1 structures 477:486 well-defined N-linked structures 455:486 well-defined N-linked structures 455:486 2014, 86, 5478-5486, noncovalent homo- and heterodimers were mis-identified as glycopeptides bearing well-defined N-linked structures, where the unexplained mass was attributed to excessive O-glycosylation. 25162384 5 12 theme components 601:610 arg1 complication 652:663 a complication 650:663 a complication in high-throughput proteomic analyses 650:701 Noncovalent dimer formation of abundant components has not previously been considered as a complication in high-throughput proteomic analyses. 25162384 5 12 theme components 601:610 arg1 formation 579:587 Noncovalent dimer formation 561:587 Noncovalent dimer formation of abundant components 561:610 Noncovalent dimer formation of abundant components has not previously been considered as a complication in high-throughput proteomic analyses. 25162384 1 13 theme Data 171:174 arg1 Function 188:195 Parallel Data Acquisition Function 162:195 Parallel Data Acquisition Function 162:195 Evidence will be presented that in the article "Novel LC-MS(2) Product Dependent Parallel Data Acquisition Function and Data Analysis Workflow for Sequencing and Identification of Intact Glycopeptides" written by Wu, S.-W.; Pu, T.-H.; Viner, R.; Khoo, K.-H. 25162384 0 14 theme Noncovalent 0:10 arg1 formation 18:26 Noncovalent dimer formation 0:26 Noncovalent dimer formation 0:26 Noncovalent dimer formation in liquid chromatography-mass spectrometry analysis. 25162384 4 15 theme unexplained 499:509 arg1 mass 511:514 the unexplained mass 495:514 the unexplained mass 495:514 2014, 86, 5478-5486, noncovalent homo- and heterodimers were mis-identified as glycopeptides bearing well-defined N-linked structures, where the unexplained mass was attributed to excessive O-glycosylation. 25162384 1 16 from article 120:126 arg1 Dependent 152:160 Dependent 152:160 Dependent 152:160 Evidence will be presented that in the article "Novel LC-MS(2) Product Dependent Parallel Data Acquisition Function and Data Analysis Workflow for Sequencing and Identification of Intact Glycopeptides" written by Wu, S.-W.; Pu, T.-H.; Viner, R.; Khoo, K.-H. 25162384 1 17 dep Product 144:150 arg1 2 141:141 2 141:141 2 141:141 Evidence will be presented that in the article "Novel LC-MS(2) Product Dependent Parallel Data Acquisition Function and Data Analysis Workflow for Sequencing and Identification of Intact Glycopeptides" written by Wu, S.-W.; Pu, T.-H.; Viner, R.; Khoo, K.-H. 25162384 1 18 theme Acquisition 176:186 arg1 Function 188:195 Parallel Data Acquisition Function 162:195 Parallel Data Acquisition Function 162:195 Evidence will be presented that in the article "Novel LC-MS(2) Product Dependent Parallel Data Acquisition Function and Data Analysis Workflow for Sequencing and Identification of Intact Glycopeptides" written by Wu, S.-W.; Pu, T.-H.; Viner, R.; Khoo, K.-H. 25162384 5 19 theme high-throughput 668:682 arg1 analyses 694:701 high-throughput proteomic analyses 668:701 high-throughput proteomic analyses 668:701 Noncovalent dimer formation of abundant components has not previously been considered as a complication in high-throughput proteomic analyses. 25162384 5 20 theme proteomic 684:692 arg1 analyses 694:701 high-throughput proteomic analyses 668:701 high-throughput proteomic analyses 668:701 Noncovalent dimer formation of abundant components has not previously been considered as a complication in high-throughput proteomic analyses. 25162384 0 21 theme chromatography-mass 38:56 arg1 analysis 71:78 liquid chromatography-mass spectrometry analysis 31:78 liquid chromatography-mass spectrometry analysis 31:78 Noncovalent dimer formation in liquid chromatography-mass spectrometry analysis. 25162384 1 22 theme Data 201:204 arg1 Workflow 215:222 Data Analysis Workflow 201:222 Data Analysis Workflow 201:222 Evidence will be presented that in the article "Novel LC-MS(2) Product Dependent Parallel Data Acquisition Function and Data Analysis Workflow for Sequencing and Identification of Intact Glycopeptides" written by Wu, S.-W.; Pu, T.-H.; Viner, R.; Khoo, K.-H. 25162384 0 23 theme liquid 31:36 arg1 analysis 71:78 liquid chromatography-mass spectrometry analysis 31:78 liquid chromatography-mass spectrometry analysis 31:78 Noncovalent dimer formation in liquid chromatography-mass spectrometry analysis. 25162384 1 24 theme Analysis 206:213 arg1 Workflow 215:222 Data Analysis Workflow 201:222 Data Analysis Workflow 201:222 Evidence will be presented that in the article "Novel LC-MS(2) Product Dependent Parallel Data Acquisition Function and Data Analysis Workflow for Sequencing and Identification of Intact Glycopeptides" written by Wu, S.-W.; Pu, T.-H.; Viner, R.; Khoo, K.-H. 25162384 4 25 theme N-linked 468:475 arg1 structures 477:486 well-defined N-linked structures 455:486 well-defined N-linked structures 455:486 2014, 86, 5478-5486, noncovalent homo- and heterodimers were mis-identified as glycopeptides bearing well-defined N-linked structures, where the unexplained mass was attributed to excessive O-glycosylation. 25162384 0 26 theme spectrometry 58:69 arg1 analysis 71:78 liquid chromatography-mass spectrometry analysis 31:78 liquid chromatography-mass spectrometry analysis 31:78 Noncovalent dimer formation in liquid chromatography-mass spectrometry analysis. 25162384 1 27 theme Novel 129:133 arg1 Product 144:150 "Novel LC-MS(2) Product 128:150 "Novel LC-MS(2) Product 128:150 Evidence will be presented that in the article "Novel LC-MS(2) Product Dependent Parallel Data Acquisition Function and Data Analysis Workflow for Sequencing and Identification of Intact Glycopeptides" written by Wu, S.-W.; Pu, T.-H.; Viner, R.; Khoo, K.-H. 25162384 5 28 from complication 652:663 arg1 analyses 694:701 high-throughput proteomic analyses 668:701 high-throughput proteomic analyses 668:701 Noncovalent dimer formation of abundant components has not previously been considered as a complication in high-throughput proteomic analyses. 25162384 0 29 dep formation 18:26 arg1 analysis 71:78 liquid chromatography-mass spectrometry analysis 31:78 liquid chromatography-mass spectrometry analysis 31:78 Noncovalent dimer formation in liquid chromatography-mass spectrometry analysis. 25162384 1 30 theme LC-MS 135:139 arg1 Product 144:150 "Novel LC-MS(2) Product 128:150 "Novel LC-MS(2) Product 128:150 Evidence will be presented that in the article "Novel LC-MS(2) Product Dependent Parallel Data Acquisition Function and Data Analysis Workflow for Sequencing and Identification of Intact Glycopeptides" written by Wu, S.-W.; Pu, T.-H.; Viner, R.; Khoo, K.-H. 25162384 1 31 from Dependent 152:160 arg1 article 120:126 the article 116:126 the article 116:126 Evidence will be presented that in the article "Novel LC-MS(2) Product Dependent Parallel Data Acquisition Function and Data Analysis Workflow for Sequencing and Identification of Intact Glycopeptides" written by Wu, S.-W.; Pu, T.-H.; Viner, R.; Khoo, K.-H. 24697810 1 0 theme chemical 158:165 arg1 synthesis 167:175 chemical synthesis 158:175 chemical synthesis 158:175 N-N-linked dimeric indole alkaloids represent an unexplored class of natural products for which chemical synthesis has no practical solution. 24697810 2 1 theme total 343:347 arg1 synthesis 349:357 the first total synthesis 333:357 the first total synthesis of dixiamycin B 333:373 To meet this challenge, an electrochemical oxidative dimerization method was developed, which was applied as the pivotal step of the first total synthesis of dixiamycin B. 24697810 1 2 theme N-N-linked 62:71 arg1 alkaloids 88:96 N-N-linked dimeric indole alkaloids 62:96 N-N-linked dimeric indole alkaloids 62:96 N-N-linked dimeric indole alkaloids represent an unexplored class of natural products for which chemical synthesis has no practical solution. 24697810 2 3 theme synthesis 349:357 arg1 which 292:296 which 292:296 which 292:296 To meet this challenge, an electrochemical oxidative dimerization method was developed, which was applied as the pivotal step of the first total synthesis of dixiamycin B. 24697810 2 3 theme synthesis 349:357 arg1 step 325:328 the pivotal step 313:328 the pivotal step of the first total synthesis of dixiamycin B 313:373 To meet this challenge, an electrochemical oxidative dimerization method was developed, which was applied as the pivotal step of the first total synthesis of dixiamycin B. 24697810 1 4 theme dimeric 73:79 arg1 alkaloids 88:96 N-N-linked dimeric indole alkaloids 62:96 N-N-linked dimeric indole alkaloids 62:96 N-N-linked dimeric indole alkaloids represent an unexplored class of natural products for which chemical synthesis has no practical solution. 24697810 3 5 theme N-N 408:410 arg1 dimerization 412:423 N-N dimerization 408:423 N-N dimerization of substituted carbazoles and β-carbolines 408:466 This method is also general for N-N dimerization of substituted carbazoles and β-carbolines, providing entry into seldom explored chemical space. 24697810 1 6 link N-N-linked 62:71 arg1 alkaloids 88:96 N-N-linked dimeric indole alkaloids 62:96 N-N-linked dimeric indole alkaloids 62:96 N-N-linked dimeric indole alkaloids represent an unexplored class of natural products for which chemical synthesis has no practical solution. 24697810 1 7 theme indole 81:86 arg1 alkaloids 88:96 N-N-linked dimeric indole alkaloids 62:96 N-N-linked dimeric indole alkaloids 62:96 N-N-linked dimeric indole alkaloids represent an unexplored class of natural products for which chemical synthesis has no practical solution. 24697810 3 8 theme substituted 428:438 arg1 carbazoles 440:449 substituted carbazoles 428:449 substituted carbazoles 428:449 This method is also general for N-N dimerization of substituted carbazoles and β-carbolines, providing entry into seldom explored chemical space. 24697810 2 9 theme pivotal 317:323 arg1 which 292:296 which 292:296 which 292:296 To meet this challenge, an electrochemical oxidative dimerization method was developed, which was applied as the pivotal step of the first total synthesis of dixiamycin B. 24697810 2 9 theme pivotal 317:323 arg1 step 325:328 the pivotal step 313:328 the pivotal step of the first total synthesis of dixiamycin B 313:373 To meet this challenge, an electrochemical oxidative dimerization method was developed, which was applied as the pivotal step of the first total synthesis of dixiamycin B. 24697810 1 10 theme practical 184:192 arg1 solution 194:201 no practical solution 181:201 no practical solution 181:201 N-N-linked dimeric indole alkaloids represent an unexplored class of natural products for which chemical synthesis has no practical solution. 24697810 0 11 theme Total 0:4 arg1 synthesis 6:14 Total synthesis 0:14 Total synthesis of dixiamycin B by electrochemical oxidation 0:59 Total synthesis of dixiamycin B by electrochemical oxidation. 24697810 2 12 theme B 373:373 arg1 synthesis 349:357 the first total synthesis 333:357 the first total synthesis of dixiamycin B 333:373 To meet this challenge, an electrochemical oxidative dimerization method was developed, which was applied as the pivotal step of the first total synthesis of dixiamycin B. 24697810 0 13 theme dixiamycin 19:28 arg1 B 30:30 dixiamycin B 19:30 dixiamycin B 19:30 Total synthesis of dixiamycin B by electrochemical oxidation. 24697810 3 14 theme β-carbolines 455:466 arg1 dimerization 412:423 N-N dimerization 408:423 N-N dimerization of substituted carbazoles and β-carbolines 408:466 This method is also general for N-N dimerization of substituted carbazoles and β-carbolines, providing entry into seldom explored chemical space. 24697810 1 15 theme unexplored 111:120 arg1 class 122:126 an unexplored class 108:126 an unexplored class of natural products for which chemical synthesis has no practical solution 108:201 N-N-linked dimeric indole alkaloids represent an unexplored class of natural products for which chemical synthesis has no practical solution. 24697810 3 16 theme explored 497:504 arg1 space 515:519 seldom explored chemical space 490:519 seldom explored chemical space 490:519 This method is also general for N-N dimerization of substituted carbazoles and β-carbolines, providing entry into seldom explored chemical space. 24697810 2 17 theme electrochemical 231:245 arg1 method 270:275 an electrochemical oxidative dimerization method 228:275 an electrochemical oxidative dimerization method 228:275 To meet this challenge, an electrochemical oxidative dimerization method was developed, which was applied as the pivotal step of the first total synthesis of dixiamycin B. 24697810 3 18 theme carbazoles 440:449 arg1 dimerization 412:423 N-N dimerization 408:423 N-N dimerization of substituted carbazoles and β-carbolines 408:466 This method is also general for N-N dimerization of substituted carbazoles and β-carbolines, providing entry into seldom explored chemical space. 24697810 0 19 theme B 30:30 arg1 synthesis 6:14 Total synthesis 0:14 Total synthesis of dixiamycin B by electrochemical oxidation 0:59 Total synthesis of dixiamycin B by electrochemical oxidation. 24697810 1 20 contain has 177:179 arg2 solution 194:201 no practical solution 181:201 no practical solution 181:201 N-N-linked dimeric indole alkaloids represent an unexplored class of natural products for which chemical synthesis has no practical solution. 24697810 1 20 contain has 177:179 arg1 synthesis 167:175 chemical synthesis 158:175 chemical synthesis 158:175 N-N-linked dimeric indole alkaloids represent an unexplored class of natural products for which chemical synthesis has no practical solution. 24697810 2 21 theme first 337:341 arg1 synthesis 349:357 the first total synthesis 333:357 the first total synthesis of dixiamycin B 333:373 To meet this challenge, an electrochemical oxidative dimerization method was developed, which was applied as the pivotal step of the first total synthesis of dixiamycin B. 24697810 0 22 theme electrochemical 35:49 arg1 oxidation 51:59 electrochemical oxidation 35:59 electrochemical oxidation 35:59 Total synthesis of dixiamycin B by electrochemical oxidation. 24697810 3 23 theme chemical 506:513 arg1 space 515:519 seldom explored chemical space 490:519 seldom explored chemical space 490:519 This method is also general for N-N dimerization of substituted carbazoles and β-carbolines, providing entry into seldom explored chemical space. 24697810 1 24 theme natural 131:137 arg1 products 139:146 natural products 131:146 natural products 131:146 N-N-linked dimeric indole alkaloids represent an unexplored class of natural products for which chemical synthesis has no practical solution. 24697810 1 25 theme products 139:146 arg1 class 122:126 an unexplored class 108:126 an unexplored class of natural products for which chemical synthesis has no practical solution 108:201 N-N-linked dimeric indole alkaloids represent an unexplored class of natural products for which chemical synthesis has no practical solution. 24697810 2 26 theme dimerization 257:268 arg1 method 270:275 an electrochemical oxidative dimerization method 228:275 an electrochemical oxidative dimerization method 228:275 To meet this challenge, an electrochemical oxidative dimerization method was developed, which was applied as the pivotal step of the first total synthesis of dixiamycin B. 24697810 2 27 theme dixiamycin 362:371 arg1 B 373:373 dixiamycin B 362:373 dixiamycin B 362:373 To meet this challenge, an electrochemical oxidative dimerization method was developed, which was applied as the pivotal step of the first total synthesis of dixiamycin B. 24697810 2 28 theme oxidative 247:255 arg1 method 270:275 an electrochemical oxidative dimerization method 228:275 an electrochemical oxidative dimerization method 228:275 To meet this challenge, an electrochemical oxidative dimerization method was developed, which was applied as the pivotal step of the first total synthesis of dixiamycin B. 28686627 4 0 theme unmodified 1069:1078 arg1 forms 1080:1084 the unmodified forms 1065:1084 the unmodified forms of proteins 1065:1096 Electrophoresis of cell lysates through a gel containing copolymerized WGA selectively induced retardation of the mobility of O-GlcNAcylated proteins, thereby allowing the simultaneous visualization of both the O-GlcNAcylated and the unmodified forms of proteins. 28686627 3 1 theme germ 757:760 arg1 WGA 774:776 WGA 774:776 WGA 774:776 Here, we describe a novel method in which O-GlcNAcylated and non-O-GlcNAcylated forms of proteins are separated by lectin affinity gel electrophoresis using wheat germ agglutinin (WGA), which primarily binds to N-acetylglucosamine residues. 28686627 3 1 theme germ 757:760 arg1 agglutinin 762:771 wheat germ agglutinin 751:771 wheat germ agglutinin (WGA) 751:777 Here, we describe a novel method in which O-GlcNAcylated and non-O-GlcNAcylated forms of proteins are separated by lectin affinity gel electrophoresis using wheat germ agglutinin (WGA), which primarily binds to N-acetylglucosamine residues. 28686627 5 2 theme proteins 1180:1187 arg1 detection 1152:1160 the quantitative detection 1135:1160 the quantitative detection of O-GlcNAcylated proteins 1135:1187 This method is therefore useful for the quantitative detection of O-GlcNAcylated proteins. 28686627 4 3 contain containing 881:890 arg1 gel 877:879 a gel 875:879 a gel containing copolymerized WGA 875:908 Electrophoresis of cell lysates through a gel containing copolymerized WGA selectively induced retardation of the mobility of O-GlcNAcylated proteins, thereby allowing the simultaneous visualization of both the O-GlcNAcylated and the unmodified forms of proteins. 28686627 4 3 contain containing 881:890 arg2 WGA 906:908 copolymerized WGA 892:908 copolymerized WGA 892:908 Electrophoresis of cell lysates through a gel containing copolymerized WGA selectively induced retardation of the mobility of O-GlcNAcylated proteins, thereby allowing the simultaneous visualization of both the O-GlcNAcylated and the unmodified forms of proteins. 28686627 0 4 theme O-GlcNAc-modified 83:99 arg1 proteins 101:108 O-GlcNAc-modified proteins 83:108 O-GlcNAc-modified proteins 83:108 WGA-based lectin affinity gel electrophoresis: A novel method for the detection of O-GlcNAc-modified proteins. 28686627 4 5 theme mobility 949:956 arg1 retardation 930:940 retardation 930:940 retardation of the mobility of O-GlcNAcylated proteins 930:983 Electrophoresis of cell lysates through a gel containing copolymerized WGA selectively induced retardation of the mobility of O-GlcNAcylated proteins, thereby allowing the simultaneous visualization of both the O-GlcNAcylated and the unmodified forms of proteins. 28686627 2 6 dep detection 506:514 arg1 the 502:504 the 502:504 the 502:504 Since conventional strategies to evaluate the O-GlcNAcylation level of a specific protein require time-consuming steps, the development of a rapid and easy method for the detection and quantification of an O-GlcNAcylated protein has been a challenging issue. 28686627 2 7 dep strategies 354:363 arg1 evaluate 368:375 evaluate 368:375 to evaluate the O-GlcNAcylation level of a specific protein 365:423 Since conventional strategies to evaluate the O-GlcNAcylation level of a specific protein require time-consuming steps, the development of a rapid and easy method for the detection and quantification of an O-GlcNAcylated protein has been a challenging issue. 28686627 0 8 theme proteins 101:108 arg1 detection 70:78 the detection 66:78 the detection of O-GlcNAc-modified proteins 66:108 WGA-based lectin affinity gel electrophoresis: A novel method for the detection of O-GlcNAc-modified proteins. 28686627 4 9 theme lysates 859:865 arg1 Electrophoresis 835:849 Electrophoresis 835:849 Electrophoresis of cell lysates through a gel containing copolymerized WGA 835:908 Electrophoresis of cell lysates through a gel containing copolymerized WGA selectively induced retardation of the mobility of O-GlcNAcylated proteins, thereby allowing the simultaneous visualization of both the O-GlcNAcylated and the unmodified forms of proteins. 28686627 2 10 theme easy 486:489 arg1 method 491:496 a rapid and easy method 474:496 a rapid and easy method for the detection and quantification of an O-GlcNAcylated protein 474:562 Since conventional strategies to evaluate the O-GlcNAcylation level of a specific protein require time-consuming steps, the development of a rapid and easy method for the detection and quantification of an O-GlcNAcylated protein has been a challenging issue. 28686627 0 11 theme lectin 10:15 arg1 electrophoresis 30:44 WGA-based lectin affinity gel electrophoresis 0:44 WGA-based lectin affinity gel electrophoresis: A novel method for the detection of O-GlcNAc-modified proteins. 0:109 WGA-based lectin affinity gel electrophoresis: A novel method for the detection of O-GlcNAc-modified proteins. 28686627 2 12 theme time-consuming 433:446 arg1 steps 448:452 time-consuming steps 433:452 time-consuming steps 433:452 Since conventional strategies to evaluate the O-GlcNAcylation level of a specific protein require time-consuming steps, the development of a rapid and easy method for the detection and quantification of an O-GlcNAcylated protein has been a challenging issue. 28686627 0 13 theme WGA-based 0:8 arg1 electrophoresis 30:44 WGA-based lectin affinity gel electrophoresis 0:44 WGA-based lectin affinity gel electrophoresis: A novel method for the detection of O-GlcNAc-modified proteins. 0:109 WGA-based lectin affinity gel electrophoresis: A novel method for the detection of O-GlcNAc-modified proteins. 28686627 5 14 theme quantitative 1139:1150 arg1 detection 1152:1160 the quantitative detection 1135:1160 the quantitative detection of O-GlcNAcylated proteins 1135:1187 This method is therefore useful for the quantitative detection of O-GlcNAcylated proteins. 28686627 1 15 with modification 130:141 arg1 O-GlcNAc 180:187 O-GlcNAc 180:187 O-GlcNAc 180:187 Post-translational modification with O-linked β-N-acetylglucosamine (O-GlcNAc) occurs selectively on serine and/or threonine residues of cytoplasmic and nuclear proteins, and dynamically regulates their molecular functions. 28686627 1 15 with modification 130:141 arg1 β-N-acetylglucosamine 157:177 O-linked β-N-acetylglucosamine 148:177 O-linked β-N-acetylglucosamine (O-GlcNAc) 148:188 Post-translational modification with O-linked β-N-acetylglucosamine (O-GlcNAc) occurs selectively on serine and/or threonine residues of cytoplasmic and nuclear proteins, and dynamically regulates their molecular functions. 28686627 0 16 theme gel 26:28 arg1 electrophoresis 30:44 WGA-based lectin affinity gel electrophoresis 0:44 WGA-based lectin affinity gel electrophoresis: A novel method for the detection of O-GlcNAc-modified proteins. 0:109 WGA-based lectin affinity gel electrophoresis: A novel method for the detection of O-GlcNAc-modified proteins. 28686627 1 17 theme molecular 314:322 arg1 functions 324:332 their molecular functions 308:332 their molecular functions 308:332 Post-translational modification with O-linked β-N-acetylglucosamine (O-GlcNAc) occurs selectively on serine and/or threonine residues of cytoplasmic and nuclear proteins, and dynamically regulates their molecular functions. 28686627 2 18 theme conventional 341:352 arg1 strategies 354:363 conventional strategies 341:363 conventional strategies to evaluate the O-GlcNAcylation level of a specific protein 341:423 Since conventional strategies to evaluate the O-GlcNAcylation level of a specific protein require time-consuming steps, the development of a rapid and easy method for the detection and quantification of an O-GlcNAcylated protein has been a challenging issue. 28686627 0 19 theme affinity 17:24 arg1 electrophoresis 30:44 WGA-based lectin affinity gel electrophoresis 0:44 WGA-based lectin affinity gel electrophoresis: A novel method for the detection of O-GlcNAc-modified proteins. 0:109 WGA-based lectin affinity gel electrophoresis: A novel method for the detection of O-GlcNAc-modified proteins. 28686627 4 20 theme simultaneous 1007:1018 arg1 visualization 1020:1032 the simultaneous visualization 1003:1032 the simultaneous visualization of both the O-GlcNAcylated and the unmodified forms of proteins 1003:1096 Electrophoresis of cell lysates through a gel containing copolymerized WGA selectively induced retardation of the mobility of O-GlcNAcylated proteins, thereby allowing the simultaneous visualization of both the O-GlcNAcylated and the unmodified forms of proteins. 28686627 4 21 theme cell 854:857 arg1 lysates 859:865 cell lysates 854:865 cell lysates 854:865 Electrophoresis of cell lysates through a gel containing copolymerized WGA selectively induced retardation of the mobility of O-GlcNAcylated proteins, thereby allowing the simultaneous visualization of both the O-GlcNAcylated and the unmodified forms of proteins. 28686627 4 22 theme forms 1080:1084 arg1 visualization 1020:1032 the simultaneous visualization 1003:1032 the simultaneous visualization of both the O-GlcNAcylated and the unmodified forms of proteins 1003:1096 Electrophoresis of cell lysates through a gel containing copolymerized WGA selectively induced retardation of the mobility of O-GlcNAcylated proteins, thereby allowing the simultaneous visualization of both the O-GlcNAcylated and the unmodified forms of proteins. 28686627 4 23 theme proteins 1089:1096 arg1 forms 1080:1084 the unmodified forms 1065:1084 the unmodified forms of proteins 1065:1096 Electrophoresis of cell lysates through a gel containing copolymerized WGA selectively induced retardation of the mobility of O-GlcNAcylated proteins, thereby allowing the simultaneous visualization of both the O-GlcNAcylated and the unmodified forms of proteins. 28686627 2 24 theme challenging 575:585 arg1 development 459:469 the development 455:469 the development of a rapid and easy method for the detection and quantification of an O-GlcNAcylated protein 455:562 Since conventional strategies to evaluate the O-GlcNAcylation level of a specific protein require time-consuming steps, the development of a rapid and easy method for the detection and quantification of an O-GlcNAcylated protein has been a challenging issue. 28686627 2 24 theme challenging 575:585 arg1 issue 587:591 a challenging issue 573:591 a challenging issue 573:591 Since conventional strategies to evaluate the O-GlcNAcylation level of a specific protein require time-consuming steps, the development of a rapid and easy method for the detection and quantification of an O-GlcNAcylated protein has been a challenging issue. 28686627 5 25 theme O-GlcNAcylated 1165:1178 arg1 proteins 1180:1187 O-GlcNAcylated proteins 1165:1187 O-GlcNAcylated proteins 1165:1187 This method is therefore useful for the quantitative detection of O-GlcNAcylated proteins. 28686627 1 26 dep serine 212:217 arg1 residues 236:243 residues 236:243 residues 236:243 Post-translational modification with O-linked β-N-acetylglucosamine (O-GlcNAc) occurs selectively on serine and/or threonine residues of cytoplasmic and nuclear proteins, and dynamically regulates their molecular functions. 28686627 2 27 theme protein 556:562 arg1 quantification 520:533 quantification 520:533 quantification 520:533 Since conventional strategies to evaluate the O-GlcNAcylation level of a specific protein require time-consuming steps, the development of a rapid and easy method for the detection and quantification of an O-GlcNAcylated protein has been a challenging issue. 28686627 2 27 theme protein 556:562 arg1 detection 506:514 detection 506:514 detection 506:514 Since conventional strategies to evaluate the O-GlcNAcylation level of a specific protein require time-consuming steps, the development of a rapid and easy method for the detection and quantification of an O-GlcNAcylated protein has been a challenging issue. 28686627 0 28 theme novel 49:53 arg1 method 55:60 A novel method 47:60 WGA-based lectin affinity gel electrophoresis: A novel method for the detection of O-GlcNAc-modified proteins. 0:109 WGA-based lectin affinity gel electrophoresis: A novel method for the detection of O-GlcNAc-modified proteins. 28686627 4 29 theme O-GlcNAcylated 961:974 arg1 proteins 976:983 O-GlcNAcylated proteins 961:983 O-GlcNAcylated proteins 961:983 Electrophoresis of cell lysates through a gel containing copolymerized WGA selectively induced retardation of the mobility of O-GlcNAcylated proteins, thereby allowing the simultaneous visualization of both the O-GlcNAcylated and the unmodified forms of proteins. 28686627 3 30 theme proteins 683:690 arg1 forms 674:678 O-GlcNAcylated and non-O-GlcNAcylated forms 636:678 O-GlcNAcylated and non-O-GlcNAcylated forms of proteins 636:690 Here, we describe a novel method in which O-GlcNAcylated and non-O-GlcNAcylated forms of proteins are separated by lectin affinity gel electrophoresis using wheat germ agglutinin (WGA), which primarily binds to N-acetylglucosamine residues. 28686627 3 31 theme novel 614:618 arg1 method 620:625 a novel method 612:625 a novel method in which O-GlcNAcylated and non-O-GlcNAcylated forms of proteins are separated by lectin affinity gel electrophoresis using wheat germ agglutinin (WGA), which primarily binds to N-acetylglucosamine residues 612:832 Here, we describe a novel method in which O-GlcNAcylated and non-O-GlcNAcylated forms of proteins are separated by lectin affinity gel electrophoresis using wheat germ agglutinin (WGA), which primarily binds to N-acetylglucosamine residues. 28686627 1 32 theme Post-translational 111:128 arg1 modification 130:141 Post-translational modification 111:141 Post-translational modification with O-linked β-N-acetylglucosamine (O-GlcNAc) 111:188 Post-translational modification with O-linked β-N-acetylglucosamine (O-GlcNAc) occurs selectively on serine and/or threonine residues of cytoplasmic and nuclear proteins, and dynamically regulates their molecular functions. 28686627 2 33 theme specific 408:415 arg1 protein 417:423 a specific protein 406:423 a specific protein 406:423 Since conventional strategies to evaluate the O-GlcNAcylation level of a specific protein require time-consuming steps, the development of a rapid and easy method for the detection and quantification of an O-GlcNAcylated protein has been a challenging issue. 28686627 4 34 theme copolymerized 892:904 arg1 WGA 906:908 copolymerized WGA 892:908 copolymerized WGA 892:908 Electrophoresis of cell lysates through a gel containing copolymerized WGA selectively induced retardation of the mobility of O-GlcNAcylated proteins, thereby allowing the simultaneous visualization of both the O-GlcNAcylated and the unmodified forms of proteins. 28686627 1 35 link O-linked 148:155 arg1 O-GlcNAc 180:187 O-GlcNAc 180:187 O-GlcNAc 180:187 Post-translational modification with O-linked β-N-acetylglucosamine (O-GlcNAc) occurs selectively on serine and/or threonine residues of cytoplasmic and nuclear proteins, and dynamically regulates their molecular functions. 28686627 1 35 link O-linked 148:155 arg1 β-N-acetylglucosamine 157:177 O-linked β-N-acetylglucosamine 148:177 O-linked β-N-acetylglucosamine (O-GlcNAc) 148:188 Post-translational modification with O-linked β-N-acetylglucosamine (O-GlcNAc) occurs selectively on serine and/or threonine residues of cytoplasmic and nuclear proteins, and dynamically regulates their molecular functions. 28686627 3 36 theme affinity 716:723 arg1 electrophoresis 729:743 lectin affinity gel electrophoresis 709:743 lectin affinity gel electrophoresis using wheat germ agglutinin (WGA), which primarily binds to N-acetylglucosamine residues 709:832 Here, we describe a novel method in which O-GlcNAcylated and non-O-GlcNAcylated forms of proteins are separated by lectin affinity gel electrophoresis using wheat germ agglutinin (WGA), which primarily binds to N-acetylglucosamine residues. 28686627 0 37 dep electrophoresis 30:44 arg1 method 55:60 A novel method 47:60 WGA-based lectin affinity gel electrophoresis: A novel method for the detection of O-GlcNAc-modified proteins. 0:109 WGA-based lectin affinity gel electrophoresis: A novel method for the detection of O-GlcNAc-modified proteins. 28686627 2 38 theme O-GlcNAcylation 381:395 arg1 level 397:401 the O-GlcNAcylation level 377:401 the O-GlcNAcylation level of a specific protein 377:423 Since conventional strategies to evaluate the O-GlcNAcylation level of a specific protein require time-consuming steps, the development of a rapid and easy method for the detection and quantification of an O-GlcNAcylated protein has been a challenging issue. 28686627 3 39 theme N-acetylglucosamine 805:823 arg1 residues 825:832 N-acetylglucosamine residues 805:832 N-acetylglucosamine residues 805:832 Here, we describe a novel method in which O-GlcNAcylated and non-O-GlcNAcylated forms of proteins are separated by lectin affinity gel electrophoresis using wheat germ agglutinin (WGA), which primarily binds to N-acetylglucosamine residues. 28686627 3 40 theme gel 725:727 arg1 electrophoresis 729:743 lectin affinity gel electrophoresis 709:743 lectin affinity gel electrophoresis using wheat germ agglutinin (WGA), which primarily binds to N-acetylglucosamine residues 709:832 Here, we describe a novel method in which O-GlcNAcylated and non-O-GlcNAcylated forms of proteins are separated by lectin affinity gel electrophoresis using wheat germ agglutinin (WGA), which primarily binds to N-acetylglucosamine residues. 28686627 3 41 theme non-O-GlcNAcylated 655:672 arg1 forms 674:678 O-GlcNAcylated and non-O-GlcNAcylated forms 636:678 O-GlcNAcylated and non-O-GlcNAcylated forms of proteins 636:690 Here, we describe a novel method in which O-GlcNAcylated and non-O-GlcNAcylated forms of proteins are separated by lectin affinity gel electrophoresis using wheat germ agglutinin (WGA), which primarily binds to N-acetylglucosamine residues. 28686627 1 42 theme cytoplasmic 248:258 arg1 proteins 272:279 cytoplasmic and nuclear proteins 248:279 cytoplasmic and nuclear proteins 248:279 Post-translational modification with O-linked β-N-acetylglucosamine (O-GlcNAc) occurs selectively on serine and/or threonine residues of cytoplasmic and nuclear proteins, and dynamically regulates their molecular functions. 28686627 4 43 theme proteins 976:983 arg1 mobility 949:956 the mobility 945:956 the mobility of O-GlcNAcylated proteins 945:983 Electrophoresis of cell lysates through a gel containing copolymerized WGA selectively induced retardation of the mobility of O-GlcNAcylated proteins, thereby allowing the simultaneous visualization of both the O-GlcNAcylated and the unmodified forms of proteins. 28686627 1 44 theme O-linked 148:155 arg1 O-GlcNAc 180:187 O-GlcNAc 180:187 O-GlcNAc 180:187 Post-translational modification with O-linked β-N-acetylglucosamine (O-GlcNAc) occurs selectively on serine and/or threonine residues of cytoplasmic and nuclear proteins, and dynamically regulates their molecular functions. 28686627 1 44 theme O-linked 148:155 arg1 β-N-acetylglucosamine 157:177 O-linked β-N-acetylglucosamine 148:177 O-linked β-N-acetylglucosamine (O-GlcNAc) 148:188 Post-translational modification with O-linked β-N-acetylglucosamine (O-GlcNAc) occurs selectively on serine and/or threonine residues of cytoplasmic and nuclear proteins, and dynamically regulates their molecular functions. 28686627 2 45 theme O-GlcNAcylated 541:554 arg1 protein 556:562 an O-GlcNAcylated protein 538:562 an O-GlcNAcylated protein 538:562 Since conventional strategies to evaluate the O-GlcNAcylation level of a specific protein require time-consuming steps, the development of a rapid and easy method for the detection and quantification of an O-GlcNAcylated protein has been a challenging issue. 28686627 3 46 theme lectin 709:714 arg1 electrophoresis 729:743 lectin affinity gel electrophoresis 709:743 lectin affinity gel electrophoresis using wheat germ agglutinin (WGA), which primarily binds to N-acetylglucosamine residues 709:832 Here, we describe a novel method in which O-GlcNAcylated and non-O-GlcNAcylated forms of proteins are separated by lectin affinity gel electrophoresis using wheat germ agglutinin (WGA), which primarily binds to N-acetylglucosamine residues. 28686627 3 47 theme O-GlcNAcylated 636:649 arg1 forms 674:678 O-GlcNAcylated and non-O-GlcNAcylated forms 636:678 O-GlcNAcylated and non-O-GlcNAcylated forms of proteins 636:690 Here, we describe a novel method in which O-GlcNAcylated and non-O-GlcNAcylated forms of proteins are separated by lectin affinity gel electrophoresis using wheat germ agglutinin (WGA), which primarily binds to N-acetylglucosamine residues. 28686627 2 48 theme protein 417:423 arg1 level 397:401 the O-GlcNAcylation level 377:401 the O-GlcNAcylation level of a specific protein 377:423 Since conventional strategies to evaluate the O-GlcNAcylation level of a specific protein require time-consuming steps, the development of a rapid and easy method for the detection and quantification of an O-GlcNAcylated protein has been a challenging issue. 28686627 1 49 theme nuclear 264:270 arg1 proteins 272:279 cytoplasmic and nuclear proteins 248:279 cytoplasmic and nuclear proteins 248:279 Post-translational modification with O-linked β-N-acetylglucosamine (O-GlcNAc) occurs selectively on serine and/or threonine residues of cytoplasmic and nuclear proteins, and dynamically regulates their molecular functions. 28686627 4 50 theme O-GlcNAcylated 1046:1059 arg1 visualization 1020:1032 the simultaneous visualization 1003:1032 the simultaneous visualization of both the O-GlcNAcylated and the unmodified forms of proteins 1003:1096 Electrophoresis of cell lysates through a gel containing copolymerized WGA selectively induced retardation of the mobility of O-GlcNAcylated proteins, thereby allowing the simultaneous visualization of both the O-GlcNAcylated and the unmodified forms of proteins. 28686627 3 51 theme wheat 751:755 arg1 WGA 774:776 WGA 774:776 WGA 774:776 Here, we describe a novel method in which O-GlcNAcylated and non-O-GlcNAcylated forms of proteins are separated by lectin affinity gel electrophoresis using wheat germ agglutinin (WGA), which primarily binds to N-acetylglucosamine residues. 28686627 3 51 theme wheat 751:755 arg1 agglutinin 762:771 wheat germ agglutinin 751:771 wheat germ agglutinin (WGA) 751:777 Here, we describe a novel method in which O-GlcNAcylated and non-O-GlcNAcylated forms of proteins are separated by lectin affinity gel electrophoresis using wheat germ agglutinin (WGA), which primarily binds to N-acetylglucosamine residues. 28686627 2 52 theme rapid 476:480 arg1 method 491:496 a rapid and easy method 474:496 a rapid and easy method for the detection and quantification of an O-GlcNAcylated protein 474:562 Since conventional strategies to evaluate the O-GlcNAcylation level of a specific protein require time-consuming steps, the development of a rapid and easy method for the detection and quantification of an O-GlcNAcylated protein has been a challenging issue. 28686627 2 53 theme method 491:496 arg1 development 459:469 the development 455:469 the development of a rapid and easy method for the detection and quantification of an O-GlcNAcylated protein 455:562 Since conventional strategies to evaluate the O-GlcNAcylation level of a specific protein require time-consuming steps, the development of a rapid and easy method for the detection and quantification of an O-GlcNAcylated protein has been a challenging issue. 28686627 2 53 theme method 491:496 arg1 issue 587:591 a challenging issue 573:591 a challenging issue 573:591 Since conventional strategies to evaluate the O-GlcNAcylation level of a specific protein require time-consuming steps, the development of a rapid and easy method for the detection and quantification of an O-GlcNAcylated protein has been a challenging issue. 28686627 1 54 theme proteins 272:279 arg1 serine 212:217 serine 212:217 serine 212:217 Post-translational modification with O-linked β-N-acetylglucosamine (O-GlcNAc) occurs selectively on serine and/or threonine residues of cytoplasmic and nuclear proteins, and dynamically regulates their molecular functions. 26775968 5 0 theme 3-O- 701:704 arg1 end-units 755:763 3-O-, 5-O- and 3,5-di-O-linked α-Araf and nonreducing end-units 701:763 3-O-, 5-O- and 3,5-di-O-linked α-Araf and nonreducing end-units of α-Araf, Arap, β-Galp and α-GlcpA 701:799 The side chains have 3-O-, 5-O- and 3,5-di-O-linked α-Araf and nonreducing end-units of α-Araf, Arap, β-Galp and α-GlcpA. 26775968 6 1 theme I 845:845 arg1 rhamnogalacturonans 847:865 type I rhamnogalacturonans 840:865 type I rhamnogalacturonans 840:865 These arabinogalactans were linked to type I rhamnogalacturonans. 26775968 5 2 contain have 696:699 arg2 end-units 755:763 3-O-, 5-O- and 3,5-di-O-linked α-Araf and nonreducing end-units 701:763 3-O-, 5-O- and 3,5-di-O-linked α-Araf and nonreducing end-units of α-Araf, Arap, β-Galp and α-GlcpA 701:799 The side chains have 3-O-, 5-O- and 3,5-di-O-linked α-Araf and nonreducing end-units of α-Araf, Arap, β-Galp and α-GlcpA. 26775968 5 2 contain have 696:699 arg1 chains 689:694 The side chains 680:694 The side chains 680:694 The side chains have 3-O-, 5-O- and 3,5-di-O-linked α-Araf and nonreducing end-units of α-Araf, Arap, β-Galp and α-GlcpA. 26775968 3 3 theme 2.8:65.8:28.5:3M 475:490 arg1 ratio 492:496 2.8:65.8:28.5:3M ratio 475:496 2.8:65.8:28.5:3M ratio 475:496 Fraction 50R was composed of rhamnose, arabinose, galactose and uronic acid in 4.3:56.2:37.4:2M ratio, respectively and fraction 10R was composed of rhamnose, arabinose, galactose and uronic acid in 2.8:65.8:28.5:3M ratio, respectively. 26775968 5 4 theme 3,5-di-O-linked 716:730 arg1 end-units 755:763 3-O-, 5-O- and 3,5-di-O-linked α-Araf and nonreducing end-units 701:763 3-O-, 5-O- and 3,5-di-O-linked α-Araf and nonreducing end-units of α-Araf, Arap, β-Galp and α-GlcpA 701:799 The side chains have 3-O-, 5-O- and 3,5-di-O-linked α-Araf and nonreducing end-units of α-Araf, Arap, β-Galp and α-GlcpA. 26775968 3 5 theme uronic 340:345 arg1 acid 347:350 uronic acid 340:350 uronic acid 340:350 Fraction 50R was composed of rhamnose, arabinose, galactose and uronic acid in 4.3:56.2:37.4:2M ratio, respectively and fraction 10R was composed of rhamnose, arabinose, galactose and uronic acid in 2.8:65.8:28.5:3M ratio, respectively. 26775968 3 6 from acid 347:350 arg1 ratio 372:376 4.3:56.2:37.4:2M ratio 355:376 4.3:56.2:37.4:2M ratio 355:376 Fraction 50R was composed of rhamnose, arabinose, galactose and uronic acid in 4.3:56.2:37.4:2M ratio, respectively and fraction 10R was composed of rhamnose, arabinose, galactose and uronic acid in 2.8:65.8:28.5:3M ratio, respectively. 26775968 4 7 link -linked 660:666 arg1 units 673:677 (1→3,6)-linked Galp units 653:677 (1→3,6)-linked Galp units 653:677 Methylation and NMR spectroscopy analyses showed that these fractions are formed by pectic arabinogalactans, which contain (1→3), (1→6) and (1→3,6)-linked Galp units. 26775968 4 8 theme -linked 660:666 arg1 units 673:677 (1→3,6)-linked Galp units 653:677 (1→3,6)-linked Galp units 653:677 Methylation and NMR spectroscopy analyses showed that these fractions are formed by pectic arabinogalactans, which contain (1→3), (1→6) and (1→3,6)-linked Galp units. 26775968 1 9 from fruit 142:146 arg1 polysaccharides 105:119 polysaccharides 105:119 polysaccharides from edible tropical fruit named starfruit (Averrhoa carambola L.) 105:186 A structural characterization of polysaccharides from edible tropical fruit named starfruit (Averrhoa carambola L.) was carried out. 26775968 1 9 from fruit 142:146 arg1 characterization 85:100 A structural characterization 72:100 A structural characterization of polysaccharides from edible tropical fruit named starfruit (Averrhoa carambola L.) 72:186 A structural characterization of polysaccharides from edible tropical fruit named starfruit (Averrhoa carambola L.) was carried out. 26775968 5 10 theme β-Galp 782:787 arg1 end-units 755:763 3-O-, 5-O- and 3,5-di-O-linked α-Araf and nonreducing end-units 701:763 3-O-, 5-O- and 3,5-di-O-linked α-Araf and nonreducing end-units of α-Araf, Arap, β-Galp and α-GlcpA 701:799 The side chains have 3-O-, 5-O- and 3,5-di-O-linked α-Araf and nonreducing end-units of α-Araf, Arap, β-Galp and α-GlcpA. 26775968 5 11 theme side 684:687 arg1 chains 689:694 The side chains 680:694 The side chains 680:694 The side chains have 3-O-, 5-O- and 3,5-di-O-linked α-Araf and nonreducing end-units of α-Araf, Arap, β-Galp and α-GlcpA. 26775968 3 12 from galactose 446:454 arg1 ratio 492:496 2.8:65.8:28.5:3M ratio 475:496 2.8:65.8:28.5:3M ratio 475:496 Fraction 50R was composed of rhamnose, arabinose, galactose and uronic acid in 4.3:56.2:37.4:2M ratio, respectively and fraction 10R was composed of rhamnose, arabinose, galactose and uronic acid in 2.8:65.8:28.5:3M ratio, respectively. 26775968 5 13 theme nonreducing 743:753 arg1 end-units 755:763 3-O-, 5-O- and 3,5-di-O-linked α-Araf and nonreducing end-units 701:763 3-O-, 5-O- and 3,5-di-O-linked α-Araf and nonreducing end-units of α-Araf, Arap, β-Galp and α-GlcpA 701:799 The side chains have 3-O-, 5-O- and 3,5-di-O-linked α-Araf and nonreducing end-units of α-Araf, Arap, β-Galp and α-GlcpA. 26775968 6 14 attach linked 830:835 arg2 arabinogalactans 808:823 These arabinogalactans 802:823 These arabinogalactans 802:823 These arabinogalactans were linked to type I rhamnogalacturonans. 26775968 6 14 attach linked 830:835 arg1 rhamnogalacturonans 847:865 type I rhamnogalacturonans 840:865 type I rhamnogalacturonans 840:865 These arabinogalactans were linked to type I rhamnogalacturonans. 26775968 0 15 theme type 7:10 arg1 II 12:13 Pectic type II 0:13 Pectic type II 0:13 Pectic type II arabinogalactans from starfruit (Averrhoa carambola L.). 26775968 5 16 theme α-GlcpA 793:799 arg1 end-units 755:763 3-O-, 5-O- and 3,5-di-O-linked α-Araf and nonreducing end-units 701:763 3-O-, 5-O- and 3,5-di-O-linked α-Araf and nonreducing end-units of α-Araf, Arap, β-Galp and α-GlcpA 701:799 The side chains have 3-O-, 5-O- and 3,5-di-O-linked α-Araf and nonreducing end-units of α-Araf, Arap, β-Galp and α-GlcpA. 26775968 0 17 theme Pectic 0:5 arg1 II 12:13 Pectic type II 0:13 Pectic type II 0:13 Pectic type II arabinogalactans from starfruit (Averrhoa carambola L.). 26775968 4 18 theme spectroscopy 533:544 arg1 analyses 546:553 Methylation and NMR spectroscopy analyses 513:553 analyses 546:553 Methylation and NMR spectroscopy analyses showed that these fractions are formed by pectic arabinogalactans, which contain (1→3), (1→6) and (1→3,6)-linked Galp units. 26775968 4 19 theme NMR 529:531 arg1 analyses 546:553 Methylation and NMR spectroscopy analyses 513:553 analyses 546:553 Methylation and NMR spectroscopy analyses showed that these fractions are formed by pectic arabinogalactans, which contain (1→3), (1→6) and (1→3,6)-linked Galp units. 26775968 3 20 from acid 467:470 arg1 ratio 492:496 2.8:65.8:28.5:3M ratio 475:496 2.8:65.8:28.5:3M ratio 475:496 Fraction 50R was composed of rhamnose, arabinose, galactose and uronic acid in 4.3:56.2:37.4:2M ratio, respectively and fraction 10R was composed of rhamnose, arabinose, galactose and uronic acid in 2.8:65.8:28.5:3M ratio, respectively. 26775968 1 21 theme structural 74:83 arg1 characterization 85:100 A structural characterization 72:100 A structural characterization of polysaccharides from edible tropical fruit named starfruit (Averrhoa carambola L.) 72:186 A structural characterization of polysaccharides from edible tropical fruit named starfruit (Averrhoa carambola L.) was carried out. 26775968 5 22 link 3,5-di-O-linked 716:730 arg1 end-units 755:763 3-O-, 5-O- and 3,5-di-O-linked α-Araf and nonreducing end-units 701:763 3-O-, 5-O- and 3,5-di-O-linked α-Araf and nonreducing end-units of α-Araf, Arap, β-Galp and α-GlcpA 701:799 The side chains have 3-O-, 5-O- and 3,5-di-O-linked α-Araf and nonreducing end-units of α-Araf, Arap, β-Galp and α-GlcpA. 26775968 5 23 theme α-Araf 768:773 arg1 end-units 755:763 3-O-, 5-O- and 3,5-di-O-linked α-Araf and nonreducing end-units 701:763 3-O-, 5-O- and 3,5-di-O-linked α-Araf and nonreducing end-units of α-Araf, Arap, β-Galp and α-GlcpA 701:799 The side chains have 3-O-, 5-O- and 3,5-di-O-linked α-Araf and nonreducing end-units of α-Araf, Arap, β-Galp and α-GlcpA. 26775968 5 24 theme 5-O- 707:710 arg1 end-units 755:763 3-O-, 5-O- and 3,5-di-O-linked α-Araf and nonreducing end-units 701:763 3-O-, 5-O- and 3,5-di-O-linked α-Araf and nonreducing end-units of α-Araf, Arap, β-Galp and α-GlcpA 701:799 The side chains have 3-O-, 5-O- and 3,5-di-O-linked α-Araf and nonreducing end-units of α-Araf, Arap, β-Galp and α-GlcpA. 26775968 3 25 from galactose 326:334 arg1 ratio 372:376 4.3:56.2:37.4:2M ratio 355:376 4.3:56.2:37.4:2M ratio 355:376 Fraction 50R was composed of rhamnose, arabinose, galactose and uronic acid in 4.3:56.2:37.4:2M ratio, respectively and fraction 10R was composed of rhamnose, arabinose, galactose and uronic acid in 2.8:65.8:28.5:3M ratio, respectively. 26775968 2 26 theme purification 215:226 arg1 steps 228:232 the purification steps 211:232 the purification steps 211:232 After the purification steps, two homogeneous fractions were obtained. 26775968 5 27 theme Arap 776:779 arg1 end-units 755:763 3-O-, 5-O- and 3,5-di-O-linked α-Araf and nonreducing end-units 701:763 3-O-, 5-O- and 3,5-di-O-linked α-Araf and nonreducing end-units of α-Araf, Arap, β-Galp and α-GlcpA 701:799 The side chains have 3-O-, 5-O- and 3,5-di-O-linked α-Araf and nonreducing end-units of α-Araf, Arap, β-Galp and α-GlcpA. 26775968 3 28 theme fraction 396:403 arg1 10R 405:407 fraction 10R 396:407 fraction 10R 396:407 Fraction 50R was composed of rhamnose, arabinose, galactose and uronic acid in 4.3:56.2:37.4:2M ratio, respectively and fraction 10R was composed of rhamnose, arabinose, galactose and uronic acid in 2.8:65.8:28.5:3M ratio, respectively. 26775968 4 29 dep contain 628:634 arg1 1→3 637:639 1→3 637:639 1→3 637:639 Methylation and NMR spectroscopy analyses showed that these fractions are formed by pectic arabinogalactans, which contain (1→3), (1→6) and (1→3,6)-linked Galp units. 26775968 3 30 from rhamnose 425:432 arg1 ratio 492:496 2.8:65.8:28.5:3M ratio 475:496 2.8:65.8:28.5:3M ratio 475:496 Fraction 50R was composed of rhamnose, arabinose, galactose and uronic acid in 4.3:56.2:37.4:2M ratio, respectively and fraction 10R was composed of rhamnose, arabinose, galactose and uronic acid in 2.8:65.8:28.5:3M ratio, respectively. 26775968 0 31 theme Averrhoa 48:55 arg1 starfruit 37:45 starfruit 37:45 starfruit (Averrhoa carambola L.) 37:69 Pectic type II arabinogalactans from starfruit (Averrhoa carambola L.). 26775968 0 31 theme Averrhoa 48:55 arg1 L 67:67 Averrhoa carambola L. 48:68 Averrhoa carambola L. 48:68 Pectic type II arabinogalactans from starfruit (Averrhoa carambola L.). 26775968 3 32 theme uronic 460:465 arg1 acid 467:470 uronic acid 460:470 uronic acid 460:470 Fraction 50R was composed of rhamnose, arabinose, galactose and uronic acid in 4.3:56.2:37.4:2M ratio, respectively and fraction 10R was composed of rhamnose, arabinose, galactose and uronic acid in 2.8:65.8:28.5:3M ratio, respectively. 26775968 5 33 theme α-Araf 732:737 arg1 end-units 755:763 3-O-, 5-O- and 3,5-di-O-linked α-Araf and nonreducing end-units 701:763 3-O-, 5-O- and 3,5-di-O-linked α-Araf and nonreducing end-units of α-Araf, Arap, β-Galp and α-GlcpA 701:799 The side chains have 3-O-, 5-O- and 3,5-di-O-linked α-Araf and nonreducing end-units of α-Araf, Arap, β-Galp and α-GlcpA. 26775968 6 34 theme type 840:843 arg1 rhamnogalacturonans 847:865 type I rhamnogalacturonans 840:865 type I rhamnogalacturonans 840:865 These arabinogalactans were linked to type I rhamnogalacturonans. 26775968 1 35 dep Averrhoa 165:172 arg1 L. 184:185 Averrhoa carambola L. 165:185 Averrhoa carambola L. 165:185 A structural characterization of polysaccharides from edible tropical fruit named starfruit (Averrhoa carambola L.) was carried out. 26775968 3 36 from arabinose 435:443 arg1 ratio 492:496 2.8:65.8:28.5:3M ratio 475:496 2.8:65.8:28.5:3M ratio 475:496 Fraction 50R was composed of rhamnose, arabinose, galactose and uronic acid in 4.3:56.2:37.4:2M ratio, respectively and fraction 10R was composed of rhamnose, arabinose, galactose and uronic acid in 2.8:65.8:28.5:3M ratio, respectively. 26775968 1 37 theme polysaccharides 105:119 arg1 characterization 85:100 A structural characterization 72:100 A structural characterization of polysaccharides from edible tropical fruit named starfruit (Averrhoa carambola L.) 72:186 A structural characterization of polysaccharides from edible tropical fruit named starfruit (Averrhoa carambola L.) was carried out. 26775968 4 38 theme Methylation 513:523 arg1 analyses 546:553 Methylation and NMR spectroscopy analyses 513:553 analyses 546:553 Methylation and NMR spectroscopy analyses showed that these fractions are formed by pectic arabinogalactans, which contain (1→3), (1→6) and (1→3,6)-linked Galp units. 26775968 3 39 theme Fraction 276:283 arg1 50R 285:287 Fraction 50R 276:287 Fraction 50R 276:287 Fraction 50R was composed of rhamnose, arabinose, galactose and uronic acid in 4.3:56.2:37.4:2M ratio, respectively and fraction 10R was composed of rhamnose, arabinose, galactose and uronic acid in 2.8:65.8:28.5:3M ratio, respectively. 26775968 3 40 from rhamnose 305:312 arg1 ratio 372:376 4.3:56.2:37.4:2M ratio 355:376 4.3:56.2:37.4:2M ratio 355:376 Fraction 50R was composed of rhamnose, arabinose, galactose and uronic acid in 4.3:56.2:37.4:2M ratio, respectively and fraction 10R was composed of rhamnose, arabinose, galactose and uronic acid in 2.8:65.8:28.5:3M ratio, respectively. 26775968 2 41 theme homogeneous 239:249 arg1 fractions 251:259 two homogeneous fractions 235:259 two homogeneous fractions 235:259 After the purification steps, two homogeneous fractions were obtained. 26775968 4 42 theme Galp 668:671 arg1 units 673:677 (1→3,6)-linked Galp units 653:677 (1→3,6)-linked Galp units 653:677 Methylation and NMR spectroscopy analyses showed that these fractions are formed by pectic arabinogalactans, which contain (1→3), (1→6) and (1→3,6)-linked Galp units. 26775968 1 43 from characterization 85:100 arg1 fruit 142:146 edible tropical fruit 126:146 edible tropical fruit named starfruit (Averrhoa carambola L.) 126:186 A structural characterization of polysaccharides from edible tropical fruit named starfruit (Averrhoa carambola L.) was carried out. 26775968 1 44 theme edible 126:131 arg1 fruit 142:146 edible tropical fruit 126:146 edible tropical fruit named starfruit (Averrhoa carambola L.) 126:186 A structural characterization of polysaccharides from edible tropical fruit named starfruit (Averrhoa carambola L.) was carried out. 26775968 3 45 from arabinose 315:323 arg1 ratio 372:376 4.3:56.2:37.4:2M ratio 355:376 4.3:56.2:37.4:2M ratio 355:376 Fraction 50R was composed of rhamnose, arabinose, galactose and uronic acid in 4.3:56.2:37.4:2M ratio, respectively and fraction 10R was composed of rhamnose, arabinose, galactose and uronic acid in 2.8:65.8:28.5:3M ratio, respectively. 26775968 1 46 theme tropical 133:140 arg1 fruit 142:146 edible tropical fruit 126:146 edible tropical fruit named starfruit (Averrhoa carambola L.) 126:186 A structural characterization of polysaccharides from edible tropical fruit named starfruit (Averrhoa carambola L.) was carried out. 26775968 0 47 theme carambola 57:65 arg1 starfruit 37:45 starfruit 37:45 starfruit (Averrhoa carambola L.) 37:69 Pectic type II arabinogalactans from starfruit (Averrhoa carambola L.). 26775968 0 47 theme carambola 57:65 arg1 L 67:67 Averrhoa carambola L. 48:68 Averrhoa carambola L. 48:68 Pectic type II arabinogalactans from starfruit (Averrhoa carambola L.). 26775968 3 48 theme 4.3:56.2:37.4:2M 355:370 arg1 ratio 372:376 4.3:56.2:37.4:2M ratio 355:376 4.3:56.2:37.4:2M ratio 355:376 Fraction 50R was composed of rhamnose, arabinose, galactose and uronic acid in 4.3:56.2:37.4:2M ratio, respectively and fraction 10R was composed of rhamnose, arabinose, galactose and uronic acid in 2.8:65.8:28.5:3M ratio, respectively. 26775968 4 49 theme pectic 597:602 arg1 1→6 644:646 1→6 644:646 1→6 644:646 Methylation and NMR spectroscopy analyses showed that these fractions are formed by pectic arabinogalactans, which contain (1→3), (1→6) and (1→3,6)-linked Galp units. 26775968 4 49 theme pectic 597:602 arg1 arabinogalactans 604:619 pectic arabinogalactans 597:619 pectic arabinogalactans 597:619 Methylation and NMR spectroscopy analyses showed that these fractions are formed by pectic arabinogalactans, which contain (1→3), (1→6) and (1→3,6)-linked Galp units. 26344496 8 0 theme PTM 1349:1351 arg1 approaches 1364:1373 PTM prediction approaches 1349:1373 PTM prediction approaches 1349:1373 Furthermore, the proposed method is compared with existing PTM prediction approaches. 26344496 4 1 theme local 640:644 arg1 information 655:665 only local sequence information 635:665 only local sequence information 635:665 Although a lot of computational approaches have been developed for PTM site prediction, currently most of them generate the predictive models by employing only local sequence information and few of them consider the relationship between different PTMs. 26344496 5 2 theme in 836:837 arg1 information 848:858 in situ PTM information 836:858 in situ PTM information 836:858 In this paper, by adopting the site-modification network (SMNet) profiles that efficiently incorporate in situ PTM information, we develop a novel method to predict PTM sites on serine and threonine. 26344496 9 3 from cross-validation 1401:1416 arg1 results 1380:1386 The results 1376:1386 The results from 10-fold cross-validation 1376:1416 The results from 10-fold cross-validation demonstrate that the proposed method with SMNet profiles performs remarkably better than existing methods, suggesting the power of SMNet profiles in identifying PTM sites. 26344496 9 4 theme PTM 1579:1581 arg1 sites 1583:1587 PTM sites 1579:1587 PTM sites 1579:1587 The results from 10-fold cross-validation demonstrate that the proposed method with SMNet profiles performs remarkably better than existing methods, suggesting the power of SMNet profiles in identifying PTM sites. 26344496 7 5 theme important 1215:1223 arg1 role 1225:1228 an important role 1212:1228 an important role 1212:1228 Performance analysis of the SVM models shows that the SMNet profiles play an important role in accurately predicting PTM sites on serine and threonine. 26344496 6 6 theme SMNet 1068:1072 arg1 profiles 1074:1081 SMNet profiles 1068:1081 SMNet profiles 1068:1081 PTM data are collected from various PTM databases and the SMNet is built to reflect the relationship between multiple PTMs, from which SMNet profiles are extracted to train predictive models based on SVM. 26344496 9 7 theme SMNet 1460:1464 arg1 profiles 1466:1473 SMNet profiles 1460:1473 SMNet profiles 1460:1473 The results from 10-fold cross-validation demonstrate that the proposed method with SMNet profiles performs remarkably better than existing methods, suggesting the power of SMNet profiles in identifying PTM sites. 26344496 5 8 theme SMNet 791:795 arg1 profiles 798:805 the site-modification network (SMNet) profiles 760:805 the site-modification network (SMNet) profiles that efficiently incorporate in situ PTM information 760:858 In this paper, by adopting the site-modification network (SMNet) profiles that efficiently incorporate in situ PTM information, we develop a novel method to predict PTM sites on serine and threonine. 26344496 7 9 theme Performance 1138:1148 arg1 analysis 1150:1157 Performance analysis 1138:1157 Performance analysis of the SVM models 1138:1175 Performance analysis of the SVM models shows that the SMNet profiles play an important role in accurately predicting PTM sites on serine and threonine. 26344496 8 10 theme prediction 1353:1362 arg1 approaches 1364:1373 PTM prediction approaches 1349:1373 PTM prediction approaches 1349:1373 Furthermore, the proposed method is compared with existing PTM prediction approaches. 26344496 4 11 theme sequence 646:653 arg1 information 655:665 only local sequence information 635:665 only local sequence information 635:665 Although a lot of computational approaches have been developed for PTM site prediction, currently most of them generate the predictive models by employing only local sequence information and few of them consider the relationship between different PTMs. 26344496 0 12 theme network 120:126 arg1 profiles 128:135 site-modification network profiles 102:135 site-modification network profiles 102:135 A novel method for predicting post-translational modifications on serine and threonine sites by using site-modification network profiles. 26344496 0 13 from modifications 49:61 arg1 threonine 77:85 threonine 77:85 threonine 77:85 A novel method for predicting post-translational modifications on serine and threonine sites by using site-modification network profiles. 26344496 0 13 from modifications 49:61 arg1 serine 66:71 serine 66:71 serine 66:71 A novel method for predicting post-translational modifications on serine and threonine sites by using site-modification network profiles. 26344496 6 14 theme predictive 1106:1115 arg1 models 1117:1122 predictive models 1106:1122 predictive models based on SVM 1106:1135 PTM data are collected from various PTM databases and the SMNet is built to reflect the relationship between multiple PTMs, from which SMNet profiles are extracted to train predictive models based on SVM. 26344496 1 15 theme many 187:190 arg1 aspects 192:198 many aspects 187:198 many aspects of biological behaviours including protein-protein interactions and cellular processes 187:285 Post-translational modifications (PTMs) regulate many aspects of biological behaviours including protein-protein interactions and cellular processes. 26344496 0 16 theme site-modification 102:118 arg1 profiles 128:135 site-modification network profiles 102:135 site-modification network profiles 102:135 A novel method for predicting post-translational modifications on serine and threonine sites by using site-modification network profiles. 26344496 4 17 theme site 551:554 arg1 prediction 556:565 PTM site prediction 547:565 PTM site prediction 547:565 Although a lot of computational approaches have been developed for PTM site prediction, currently most of them generate the predictive models by employing only local sequence information and few of them consider the relationship between different PTMs. 26344496 7 18 theme models 1170:1175 arg1 analysis 1150:1157 Performance analysis 1138:1157 Performance analysis of the SVM models 1138:1175 Performance analysis of the SVM models shows that the SMNet profiles play an important role in accurately predicting PTM sites on serine and threonine. 26344496 4 19 theme different 717:725 arg1 PTMs 727:730 different PTMs 717:730 different PTMs 717:730 Although a lot of computational approaches have been developed for PTM site prediction, currently most of them generate the predictive models by employing only local sequence information and few of them consider the relationship between different PTMs. 26344496 0 20 theme novel 2:6 arg1 method 8:13 A novel method 0:13 A novel method for predicting post-translational modifications on serine and threonine sites by using site-modification network profiles. 0:136 A novel method for predicting post-translational modifications on serine and threonine sites by using site-modification network profiles. 26344496 4 21 theme PTM 547:549 arg1 prediction 556:565 PTM site prediction 547:565 PTM site prediction 547:565 Although a lot of computational approaches have been developed for PTM site prediction, currently most of them generate the predictive models by employing only local sequence information and few of them consider the relationship between different PTMs. 26344496 6 22 theme PTM 933:935 arg1 data 937:940 PTM data 933:940 PTM data 933:940 PTM data are collected from various PTM databases and the SMNet is built to reflect the relationship between multiple PTMs, from which SMNet profiles are extracted to train predictive models based on SVM. 26344496 3 23 theme O-linked 440:447 arg1 glycosylation 449:461 O-linked glycosylation 440:461 O-linked glycosylation 440:461 The PTMs on serine and threonine sites include phosphorylation, O-linked glycosylation and acetylation. 26344496 2 24 theme regulatory 353:362 arg1 mechanisms 364:373 the PTM regulatory mechanisms 345:373 the PTM regulatory mechanisms 345:373 Identification of PTM sites is helpful for understanding the PTM regulatory mechanisms. 26344496 1 25 theme biological 203:212 arg1 processes 277:285 cellular processes 268:285 cellular processes 268:285 Post-translational modifications (PTMs) regulate many aspects of biological behaviours including protein-protein interactions and cellular processes. 26344496 1 25 theme biological 203:212 arg1 behaviours 214:223 biological behaviours 203:223 biological behaviours including protein-protein interactions and cellular processes 203:285 Post-translational modifications (PTMs) regulate many aspects of biological behaviours including protein-protein interactions and cellular processes. 26344496 1 25 theme biological 203:212 arg1 interactions 251:262 protein-protein interactions 235:262 protein-protein interactions 235:262 Post-translational modifications (PTMs) regulate many aspects of biological behaviours including protein-protein interactions and cellular processes. 26344496 4 26 theme predictive 604:613 arg1 models 615:620 the predictive models 600:620 the predictive models 600:620 Although a lot of computational approaches have been developed for PTM site prediction, currently most of them generate the predictive models by employing only local sequence information and few of them consider the relationship between different PTMs. 26344496 2 27 theme PTM 349:351 arg1 mechanisms 364:373 the PTM regulatory mechanisms 345:373 the PTM regulatory mechanisms 345:373 Identification of PTM sites is helpful for understanding the PTM regulatory mechanisms. 26344496 1 28 theme behaviours 214:223 arg1 aspects 192:198 many aspects 187:198 many aspects of biological behaviours including protein-protein interactions and cellular processes 187:285 Post-translational modifications (PTMs) regulate many aspects of biological behaviours including protein-protein interactions and cellular processes. 26344496 5 29 theme novel 874:878 arg1 method 880:885 a novel method 872:885 a novel method to predict PTM sites on serine and threonine 872:930 In this paper, by adopting the site-modification network (SMNet) profiles that efficiently incorporate in situ PTM information, we develop a novel method to predict PTM sites on serine and threonine. 26344496 5 30 dep in 836:837 arg1 situ 839:842 situ 839:842 situ 839:842 In this paper, by adopting the site-modification network (SMNet) profiles that efficiently incorporate in situ PTM information, we develop a novel method to predict PTM sites on serine and threonine. 26344496 4 31 theme approaches 512:521 arg1 lot 491:493 a lot 489:493 a lot of computational approaches 489:521 Although a lot of computational approaches have been developed for PTM site prediction, currently most of them generate the predictive models by employing only local sequence information and few of them consider the relationship between different PTMs. 26344496 4 31 theme approaches 512:521 arg1 approaches 512:521 computational approaches 498:521 computational approaches 498:521 Although a lot of computational approaches have been developed for PTM site prediction, currently most of them generate the predictive models by employing only local sequence information and few of them consider the relationship between different PTMs. 26344496 0 32 dep serine 66:71 arg1 sites 87:91 sites 87:91 sites 87:91 A novel method for predicting post-translational modifications on serine and threonine sites by using site-modification network profiles. 26344496 0 33 theme post-translational 30:47 arg1 modifications 49:61 post-translational modifications 30:61 post-translational modifications on serine and threonine sites 30:91 A novel method for predicting post-translational modifications on serine and threonine sites by using site-modification network profiles. 26344496 5 34 theme site-modification 764:780 arg1 profiles 798:805 the site-modification network (SMNet) profiles 760:805 the site-modification network (SMNet) profiles that efficiently incorporate in situ PTM information 760:858 In this paper, by adopting the site-modification network (SMNet) profiles that efficiently incorporate in situ PTM information, we develop a novel method to predict PTM sites on serine and threonine. 26344496 4 35 theme computational 498:510 arg1 approaches 512:521 computational approaches 498:521 computational approaches 498:521 Although a lot of computational approaches have been developed for PTM site prediction, currently most of them generate the predictive models by employing only local sequence information and few of them consider the relationship between different PTMs. 26344496 1 36 theme protein-protein 235:249 arg1 interactions 251:262 protein-protein interactions 235:262 protein-protein interactions 235:262 Post-translational modifications (PTMs) regulate many aspects of biological behaviours including protein-protein interactions and cellular processes. 26344496 5 37 theme PTM 844:846 arg1 information 848:858 in situ PTM information 836:858 in situ PTM information 836:858 In this paper, by adopting the site-modification network (SMNet) profiles that efficiently incorporate in situ PTM information, we develop a novel method to predict PTM sites on serine and threonine. 26344496 5 38 theme network 782:788 arg1 profiles 798:805 the site-modification network (SMNet) profiles 760:805 the site-modification network (SMNet) profiles that efficiently incorporate in situ PTM information 760:858 In this paper, by adopting the site-modification network (SMNet) profiles that efficiently incorporate in situ PTM information, we develop a novel method to predict PTM sites on serine and threonine. 26344496 8 39 dep existing 1340:1347 arg1 is 1323:1324 is 1323:1324 is compared with existing PTM prediction approaches 1323:1373 Furthermore, the proposed method is compared with existing PTM prediction approaches. 26344496 5 40 theme PTM 898:900 arg1 sites 902:906 PTM sites 898:906 PTM sites 898:906 In this paper, by adopting the site-modification network (SMNet) profiles that efficiently incorporate in situ PTM information, we develop a novel method to predict PTM sites on serine and threonine. 26344496 3 41 dep serine 388:393 arg1 sites 409:413 sites 409:413 sites 409:413 The PTMs on serine and threonine sites include phosphorylation, O-linked glycosylation and acetylation. 26344496 8 42 theme proposed 1307:1314 arg1 method 1316:1321 the proposed method 1303:1321 the proposed method 1303:1321 Furthermore, the proposed method is compared with existing PTM prediction approaches. 26344496 7 43 theme SVM 1166:1168 arg1 models 1170:1175 the SVM models 1162:1175 the SVM models 1162:1175 Performance analysis of the SVM models shows that the SMNet profiles play an important role in accurately predicting PTM sites on serine and threonine. 26344496 9 44 theme 10-fold 1393:1399 arg1 cross-validation 1401:1416 10-fold cross-validation 1393:1416 10-fold cross-validation 1393:1416 The results from 10-fold cross-validation demonstrate that the proposed method with SMNet profiles performs remarkably better than existing methods, suggesting the power of SMNet profiles in identifying PTM sites. 26344496 9 45 with method 1448:1453 arg1 profiles 1466:1473 SMNet profiles 1460:1473 SMNet profiles 1460:1473 The results from 10-fold cross-validation demonstrate that the proposed method with SMNet profiles performs remarkably better than existing methods, suggesting the power of SMNet profiles in identifying PTM sites. 26344496 6 46 theme PTM 969:971 arg1 databases 973:981 various PTM databases 961:981 various PTM databases 961:981 PTM data are collected from various PTM databases and the SMNet is built to reflect the relationship between multiple PTMs, from which SMNet profiles are extracted to train predictive models based on SVM. 26344496 2 47 theme sites 310:314 arg1 Identification 288:301 Identification 288:301 Identification of PTM sites 288:314 Identification of PTM sites is helpful for understanding the PTM regulatory mechanisms. 26344496 1 48 theme Post-translational 138:155 arg1 PTMs 172:175 PTMs 172:175 PTMs 172:175 Post-translational modifications (PTMs) regulate many aspects of biological behaviours including protein-protein interactions and cellular processes. 26344496 1 48 theme Post-translational 138:155 arg1 modifications 157:169 Post-translational modifications 138:169 Post-translational modifications (PTMs) 138:176 Post-translational modifications (PTMs) regulate many aspects of biological behaviours including protein-protein interactions and cellular processes. 26344496 3 49 from PTMs 380:383 arg1 threonine 399:407 threonine 399:407 threonine 399:407 The PTMs on serine and threonine sites include phosphorylation, O-linked glycosylation and acetylation. 26344496 3 49 from PTMs 380:383 arg1 serine 388:393 serine 388:393 serine 388:393 The PTMs on serine and threonine sites include phosphorylation, O-linked glycosylation and acetylation. 26344496 2 50 theme PTM 306:308 arg1 sites 310:314 PTM sites 306:314 PTM sites 306:314 Identification of PTM sites is helpful for understanding the PTM regulatory mechanisms. 26344496 9 51 theme SMNet 1549:1553 arg1 profiles 1555:1562 SMNet profiles 1549:1562 SMNet profiles 1549:1562 The results from 10-fold cross-validation demonstrate that the proposed method with SMNet profiles performs remarkably better than existing methods, suggesting the power of SMNet profiles in identifying PTM sites. 26344496 1 52 theme cellular 268:275 arg1 processes 277:285 cellular processes 268:285 cellular processes 268:285 Post-translational modifications (PTMs) regulate many aspects of biological behaviours including protein-protein interactions and cellular processes. 26344496 9 53 theme existing 1507:1514 arg1 methods 1516:1522 existing methods 1507:1522 existing methods 1507:1522 The results from 10-fold cross-validation demonstrate that the proposed method with SMNet profiles performs remarkably better than existing methods, suggesting the power of SMNet profiles in identifying PTM sites. 26344496 9 54 theme profiles 1555:1562 arg1 power 1540:1544 the power 1536:1544 the power of SMNet profiles in identifying PTM sites 1536:1587 The results from 10-fold cross-validation demonstrate that the proposed method with SMNet profiles performs remarkably better than existing methods, suggesting the power of SMNet profiles in identifying PTM sites. 26344496 4 55 theme them 678:681 arg1 few 671:673 few 671:673 few 671:673 Although a lot of computational approaches have been developed for PTM site prediction, currently most of them generate the predictive models by employing only local sequence information and few of them consider the relationship between different PTMs. 26344496 7 56 theme PTM 1255:1257 arg1 sites 1259:1263 PTM sites 1255:1263 PTM sites 1255:1263 Performance analysis of the SVM models shows that the SMNet profiles play an important role in accurately predicting PTM sites on serine and threonine. 26344496 6 57 theme various 961:967 arg1 databases 973:981 various PTM databases 961:981 various PTM databases 961:981 PTM data are collected from various PTM databases and the SMNet is built to reflect the relationship between multiple PTMs, from which SMNet profiles are extracted to train predictive models based on SVM. 26344496 3 58 link O-linked 440:447 arg1 glycosylation 449:461 O-linked glycosylation 440:461 O-linked glycosylation 440:461 The PTMs on serine and threonine sites include phosphorylation, O-linked glycosylation and acetylation. 26344496 7 59 theme SMNet 1192:1196 arg1 profiles 1198:1205 the SMNet profiles 1188:1205 the SMNet profiles 1188:1205 Performance analysis of the SVM models shows that the SMNet profiles play an important role in accurately predicting PTM sites on serine and threonine. 26344496 9 60 theme proposed 1439:1446 arg1 method 1448:1453 the proposed method 1435:1453 the proposed method with SMNet profiles 1435:1473 The results from 10-fold cross-validation demonstrate that the proposed method with SMNet profiles performs remarkably better than existing methods, suggesting the power of SMNet profiles in identifying PTM sites. 26344496 6 61 theme multiple 1042:1049 arg1 PTMs 1051:1054 multiple PTMs 1042:1054 multiple PTMs 1042:1054 PTM data are collected from various PTM databases and the SMNet is built to reflect the relationship between multiple PTMs, from which SMNet profiles are extracted to train predictive models based on SVM. 25587705 8 0 theme substantial 996:1006 arg1 link 1008:1011 a substantial link 994:1011 a substantial link between glycosylation signature and diabetes progression 994:1068 Our data confirm a substantial link between glycosylation signature and diabetes progression. 25587705 6 1 from differences 736:746 arg1 expression 764:773 glycoprotein expression 751:773 glycoprotein expression 751:773 The lectins UEAI, PHA-E, GSI, PNA, and RCA identified remarkable disease-associated differences in glycoprotein expression. 25587705 2 2 gly glycoproteins 287:299 arg1 glycoproteins 287:299 N- and O-linked glycoproteins 271:299 N- and O-linked glycoproteins 271:299 Hyperglycemia per se is expected to have a direct impact on the biosynthesis of N- and O-linked glycoproteins. 25587705 4 3 theme time 538:541 arg1 points 543:548 three different time points 522:548 three different time points post streptozotocin injection 522:578 Kidneys of streptozotocin-diabetic and control rats were harvested at three different time points post streptozotocin injection. 25587705 8 4 theme glycosylation 1021:1033 arg1 signature 1035:1043 glycosylation signature 1021:1043 glycosylation signature 1021:1043 Our data confirm a substantial link between glycosylation signature and diabetes progression. 25587705 4 5 theme streptozotocin-diabetic 463:485 arg1 Kidneys 452:458 Kidneys 452:458 Kidneys of streptozotocin-diabetic and control rats 452:502 Kidneys of streptozotocin-diabetic and control rats were harvested at three different time points post streptozotocin injection. 25587705 10 6 theme unexplored 1278:1287 arg1 potential 1289:1297 the unexplored potential 1274:1297 the unexplored potential of protein glycosylation analysis in the discovery of molecules linked to diabetic kidney disease 1274:1395 Thus, our study demonstrates the unexplored potential of protein glycosylation analysis in the discovery of molecules linked to diabetic kidney disease. 25587705 4 7 dep streptozotocin-diabetic 463:485 arg1 rats 499:502 rats 499:502 rats 499:502 Kidneys of streptozotocin-diabetic and control rats were harvested at three different time points post streptozotocin injection. 25587705 4 8 theme different 528:536 arg1 points 543:548 three different time points 522:548 three different time points post streptozotocin injection 522:578 Kidneys of streptozotocin-diabetic and control rats were harvested at three different time points post streptozotocin injection. 25587705 10 9 theme analysis 1324:1331 arg1 potential 1289:1297 the unexplored potential 1274:1297 the unexplored potential of protein glycosylation analysis in the discovery of molecules linked to diabetic kidney disease 1274:1395 Thus, our study demonstrates the unexplored potential of protein glycosylation analysis in the discovery of molecules linked to diabetic kidney disease. 25587705 9 10 theme dipeptidyl 1116:1125 arg1 peptidase-IV 1127:1138 dipeptidyl peptidase-IV 1116:1138 dipeptidyl peptidase-IV 1116:1138 Furthermore, as suggested by our findings on dipeptidyl peptidase-IV, altered protein glycosylation may reflect changes in biochemical properties such as enzymatic activity. 25587705 3 11 theme protein 348:354 arg1 glycosylation 356:368 protein glycosylation 348:368 protein glycosylation 348:368 This study aims to establish the link between protein glycosylation and progression of experimental diabetic kidney disease using orthogonal methods. 25587705 2 12 theme N- 271:272 arg1 glycoproteins 287:299 N- and O-linked glycoproteins 271:299 N- and O-linked glycoproteins 271:299 Hyperglycemia per se is expected to have a direct impact on the biosynthesis of N- and O-linked glycoproteins. 25587705 7 13 theme glycoproteins 884:896 arg1 identification 858:871 the identification 854:871 the identification of several glycoproteins involved in salt-handling, angiogenesis, and extracellular matrix degradation 854:974 Lectin affinity chromatography followed by mass spectrometric analyses led to the identification of several glycoproteins involved in salt-handling, angiogenesis, and extracellular matrix degradation. 25587705 6 14 gly glycoprotein 751:762 arg1 glycoprotein 751:762 glycoprotein expression 751:773 glycoprotein expression 751:773 The lectins UEAI, PHA-E, GSI, PNA, and RCA identified remarkable disease-associated differences in glycoprotein expression. 25587705 8 15 theme diabetes 1049:1056 arg1 progression 1058:1068 diabetes progression 1049:1068 diabetes progression 1049:1068 Our data confirm a substantial link between glycosylation signature and diabetes progression. 25587705 4 16 theme control 491:497 arg1 Kidneys 452:458 Kidneys 452:458 Kidneys of streptozotocin-diabetic and control rats 452:502 Kidneys of streptozotocin-diabetic and control rats were harvested at three different time points post streptozotocin injection. 25587705 10 17 theme diabetic 1373:1380 arg1 disease 1389:1395 diabetic kidney disease 1373:1395 diabetic kidney disease 1373:1395 Thus, our study demonstrates the unexplored potential of protein glycosylation analysis in the discovery of molecules linked to diabetic kidney disease. 25587705 7 18 theme several 876:882 arg1 glycoproteins 884:896 several glycoproteins 876:896 several glycoproteins involved in salt-handling, angiogenesis, and extracellular matrix degradation 876:974 Lectin affinity chromatography followed by mass spectrometric analyses led to the identification of several glycoproteins involved in salt-handling, angiogenesis, and extracellular matrix degradation. 25587705 1 19 theme renal 164:168 arg1 therapy 182:188 renal replacement therapy 164:188 renal replacement therapy 164:188 Diabetic nephropathy often progresses to end-stage kidney disease and, ultimately, to renal replacement therapy. 25587705 5 20 theme lectin 638:643 arg1 blots 645:649 lectin blots 638:649 lectin blots 638:649 A panel of 12 plant lectins was used in the screening of lectin blots. 25587705 1 21 theme Diabetic 78:85 arg1 nephropathy 87:97 Diabetic nephropathy 78:97 Diabetic nephropathy 78:97 Diabetic nephropathy often progresses to end-stage kidney disease and, ultimately, to renal replacement therapy. 25587705 9 22 theme altered 1141:1147 arg1 glycosylation 1157:1169 altered protein glycosylation 1141:1169 altered protein glycosylation 1141:1169 Furthermore, as suggested by our findings on dipeptidyl peptidase-IV, altered protein glycosylation may reflect changes in biochemical properties such as enzymatic activity. 25587705 1 23 theme replacement 170:180 arg1 therapy 182:188 renal replacement therapy 164:188 renal replacement therapy 164:188 Diabetic nephropathy often progresses to end-stage kidney disease and, ultimately, to renal replacement therapy. 25587705 10 24 attach linked 1363:1368 arg2 molecules 1353:1361 molecules 1353:1361 molecules linked to diabetic kidney disease 1353:1395 Thus, our study demonstrates the unexplored potential of protein glycosylation analysis in the discovery of molecules linked to diabetic kidney disease. 25587705 10 24 attach linked 1363:1368 arg1 disease 1389:1395 diabetic kidney disease 1373:1395 diabetic kidney disease 1373:1395 Thus, our study demonstrates the unexplored potential of protein glycosylation analysis in the discovery of molecules linked to diabetic kidney disease. 25587705 5 25 theme blots 645:649 arg1 screening 625:633 the screening 621:633 the screening of lectin blots 621:649 A panel of 12 plant lectins was used in the screening of lectin blots. 25587705 5 26 theme plant 595:599 arg1 lectins 601:607 12 plant lectins 592:607 12 plant lectins 592:607 A panel of 12 plant lectins was used in the screening of lectin blots. 25587705 7 27 gly glycoproteins 884:896 arg1 glycoproteins 884:896 several glycoproteins 876:896 several glycoproteins involved in salt-handling, angiogenesis, and extracellular matrix degradation 876:974 Lectin affinity chromatography followed by mass spectrometric analyses led to the identification of several glycoproteins involved in salt-handling, angiogenesis, and extracellular matrix degradation. 25587705 0 28 theme Glycosylation 0:12 arg1 patterns 14:21 Glycosylation patterns 0:21 Glycosylation patterns of kidney proteins 0:40 Glycosylation patterns of kidney proteins differ in rat diabetic nephropathy. 25587705 7 29 theme spectrometric 824:836 arg1 analyses 838:845 mass spectrometric analyses 819:845 mass spectrometric analyses 819:845 Lectin affinity chromatography followed by mass spectrometric analyses led to the identification of several glycoproteins involved in salt-handling, angiogenesis, and extracellular matrix degradation. 25587705 3 30 gly glycosylation 356:368 arg1 disease 418:424 experimental diabetic kidney disease 389:424 experimental diabetic kidney disease 389:424 This study aims to establish the link between protein glycosylation and progression of experimental diabetic kidney disease using orthogonal methods. 25587705 5 31 theme lectins 601:607 arg1 panel 583:587 A panel 581:587 A panel of 12 plant lectins 581:607 A panel of 12 plant lectins was used in the screening of lectin blots. 25587705 3 32 theme orthogonal 432:441 arg1 methods 443:449 orthogonal methods 432:449 orthogonal methods 432:449 This study aims to establish the link between protein glycosylation and progression of experimental diabetic kidney disease using orthogonal methods. 25587705 0 33 theme kidney 26:31 arg1 proteins 33:40 kidney proteins 26:40 kidney proteins 26:40 Glycosylation patterns of kidney proteins differ in rat diabetic nephropathy. 25587705 2 34 theme glycoproteins 287:299 arg1 biosynthesis 255:266 the biosynthesis 251:266 the biosynthesis of N- and O-linked glycoproteins 251:299 Hyperglycemia per se is expected to have a direct impact on the biosynthesis of N- and O-linked glycoproteins. 25587705 9 35 theme enzymatic 1225:1233 arg1 activity 1235:1242 enzymatic activity 1225:1242 enzymatic activity 1225:1242 Furthermore, as suggested by our findings on dipeptidyl peptidase-IV, altered protein glycosylation may reflect changes in biochemical properties such as enzymatic activity. 25587705 9 36 theme protein 1149:1155 arg1 glycosylation 1157:1169 altered protein glycosylation 1141:1169 altered protein glycosylation 1141:1169 Furthermore, as suggested by our findings on dipeptidyl peptidase-IV, altered protein glycosylation may reflect changes in biochemical properties such as enzymatic activity. 25587705 2 37 theme O-linked 278:285 arg1 glycoproteins 287:299 N- and O-linked glycoproteins 271:299 N- and O-linked glycoproteins 271:299 Hyperglycemia per se is expected to have a direct impact on the biosynthesis of N- and O-linked glycoproteins. 25587705 3 38 theme kidney 411:416 arg1 disease 418:424 experimental diabetic kidney disease 389:424 experimental diabetic kidney disease 389:424 This study aims to establish the link between protein glycosylation and progression of experimental diabetic kidney disease using orthogonal methods. 25587705 7 39 theme mass 819:822 arg1 analyses 838:845 mass spectrometric analyses 819:845 mass spectrometric analyses 819:845 Lectin affinity chromatography followed by mass spectrometric analyses led to the identification of several glycoproteins involved in salt-handling, angiogenesis, and extracellular matrix degradation. 25587705 5 40 used used 613:616 arg2 panel 583:587 A panel 581:587 A panel of 12 plant lectins 581:607 A panel of 12 plant lectins was used in the screening of lectin blots. 25587705 0 41 theme proteins 33:40 arg1 patterns 14:21 Glycosylation patterns 0:21 Glycosylation patterns of kidney proteins 0:40 Glycosylation patterns of kidney proteins differ in rat diabetic nephropathy. 25587705 3 42 theme disease 418:424 arg1 progression 374:384 progression 374:384 progression of experimental diabetic kidney disease 374:424 This study aims to establish the link between protein glycosylation and progression of experimental diabetic kidney disease using orthogonal methods. 25587705 3 42 theme disease 418:424 arg1 glycosylation 356:368 protein glycosylation 348:368 protein glycosylation 348:368 This study aims to establish the link between protein glycosylation and progression of experimental diabetic kidney disease using orthogonal methods. 25587705 9 43 from changes 1183:1189 arg1 properties 1206:1215 biochemical properties 1194:1215 biochemical properties such as enzymatic activity 1194:1242 Furthermore, as suggested by our findings on dipeptidyl peptidase-IV, altered protein glycosylation may reflect changes in biochemical properties such as enzymatic activity. 25587705 9 43 from changes 1183:1189 arg1 activity 1235:1242 enzymatic activity 1225:1242 enzymatic activity 1225:1242 Furthermore, as suggested by our findings on dipeptidyl peptidase-IV, altered protein glycosylation may reflect changes in biochemical properties such as enzymatic activity. 25587705 7 44 theme affinity 783:790 arg1 chromatography 792:805 Lectin affinity chromatography 776:805 Lectin affinity chromatography followed by mass spectrometric analyses 776:845 Lectin affinity chromatography followed by mass spectrometric analyses led to the identification of several glycoproteins involved in salt-handling, angiogenesis, and extracellular matrix degradation. 25587705 3 45 theme experimental 389:400 arg1 disease 418:424 experimental diabetic kidney disease 389:424 experimental diabetic kidney disease 389:424 This study aims to establish the link between protein glycosylation and progression of experimental diabetic kidney disease using orthogonal methods. 25587705 2 46 link O-linked 278:285 arg1 glycoproteins 287:299 N- and O-linked glycoproteins 271:299 N- and O-linked glycoproteins 271:299 Hyperglycemia per se is expected to have a direct impact on the biosynthesis of N- and O-linked glycoproteins. 25587705 10 47 theme kidney 1382:1387 arg1 disease 1389:1395 diabetic kidney disease 1373:1395 diabetic kidney disease 1373:1395 Thus, our study demonstrates the unexplored potential of protein glycosylation analysis in the discovery of molecules linked to diabetic kidney disease. 25587705 0 48 theme diabetic 56:63 arg1 nephropathy 65:75 rat diabetic nephropathy 52:75 rat diabetic nephropathy 52:75 Glycosylation patterns of kidney proteins differ in rat diabetic nephropathy. 25587705 9 49 theme biochemical 1194:1204 arg1 properties 1206:1215 biochemical properties 1194:1215 biochemical properties such as enzymatic activity 1194:1242 Furthermore, as suggested by our findings on dipeptidyl peptidase-IV, altered protein glycosylation may reflect changes in biochemical properties such as enzymatic activity. 25587705 9 49 theme biochemical 1194:1204 arg1 activity 1235:1242 enzymatic activity 1225:1242 enzymatic activity 1225:1242 Furthermore, as suggested by our findings on dipeptidyl peptidase-IV, altered protein glycosylation may reflect changes in biochemical properties such as enzymatic activity. 25587705 1 50 theme end-stage 119:127 arg1 disease 136:142 end-stage kidney disease 119:142 end-stage kidney disease 119:142 Diabetic nephropathy often progresses to end-stage kidney disease and, ultimately, to renal replacement therapy. 25587705 3 51 theme diabetic 402:409 arg1 disease 418:424 experimental diabetic kidney disease 389:424 experimental diabetic kidney disease 389:424 This study aims to establish the link between protein glycosylation and progression of experimental diabetic kidney disease using orthogonal methods. 25587705 7 52 theme Lectin 776:781 arg1 chromatography 792:805 Lectin affinity chromatography 776:805 Lectin affinity chromatography followed by mass spectrometric analyses 776:845 Lectin affinity chromatography followed by mass spectrometric analyses led to the identification of several glycoproteins involved in salt-handling, angiogenesis, and extracellular matrix degradation. 25587705 6 53 theme glycoprotein 751:762 arg1 expression 764:773 glycoprotein expression 751:773 glycoprotein expression 751:773 The lectins UEAI, PHA-E, GSI, PNA, and RCA identified remarkable disease-associated differences in glycoprotein expression. 25587705 1 54 theme kidney 129:134 arg1 disease 136:142 end-stage kidney disease 119:142 end-stage kidney disease 119:142 Diabetic nephropathy often progresses to end-stage kidney disease and, ultimately, to renal replacement therapy. 25587705 7 55 theme extracellular 943:955 arg1 degradation 964:974 extracellular matrix degradation 943:974 extracellular matrix degradation 943:974 Lectin affinity chromatography followed by mass spectrometric analyses led to the identification of several glycoproteins involved in salt-handling, angiogenesis, and extracellular matrix degradation. 25587705 4 56 theme streptozotocin 555:568 arg1 injection 570:578 streptozotocin injection 555:578 streptozotocin injection 555:578 Kidneys of streptozotocin-diabetic and control rats were harvested at three different time points post streptozotocin injection. 25587705 10 57 from potential 1289:1297 arg1 discovery 1340:1348 the discovery 1336:1348 the discovery of molecules linked to diabetic kidney disease 1336:1395 Thus, our study demonstrates the unexplored potential of protein glycosylation analysis in the discovery of molecules linked to diabetic kidney disease. 25587705 7 58 theme matrix 957:962 arg1 degradation 964:974 extracellular matrix degradation 943:974 extracellular matrix degradation 943:974 Lectin affinity chromatography followed by mass spectrometric analyses led to the identification of several glycoproteins involved in salt-handling, angiogenesis, and extracellular matrix degradation. 25587705 9 59 from findings 1104:1111 arg1 peptidase-IV 1127:1138 dipeptidyl peptidase-IV 1116:1138 dipeptidyl peptidase-IV 1116:1138 Furthermore, as suggested by our findings on dipeptidyl peptidase-IV, altered protein glycosylation may reflect changes in biochemical properties such as enzymatic activity. 25587705 10 60 theme molecules 1353:1361 arg1 discovery 1340:1348 the discovery 1336:1348 the discovery of molecules linked to diabetic kidney disease 1336:1395 Thus, our study demonstrates the unexplored potential of protein glycosylation analysis in the discovery of molecules linked to diabetic kidney disease. 25587705 6 61 dep lectins 656:662 arg1 RCA 691:693 RCA 691:693 RCA 691:693 The lectins UEAI, PHA-E, GSI, PNA, and RCA identified remarkable disease-associated differences in glycoprotein expression. 25587705 6 61 dep lectins 656:662 arg1 PHA-E 670:674 PHA-E 670:674 PHA-E 670:674 The lectins UEAI, PHA-E, GSI, PNA, and RCA identified remarkable disease-associated differences in glycoprotein expression. 25587705 6 61 dep lectins 656:662 arg1 GSI 677:679 GSI 677:679 GSI 677:679 The lectins UEAI, PHA-E, GSI, PNA, and RCA identified remarkable disease-associated differences in glycoprotein expression. 25587705 6 61 dep lectins 656:662 arg1 lectins 656:662 The lectins UEAI, PHA-E, GSI, PNA, and RCA 652:693 The lectins UEAI, PHA-E, GSI, PNA, and RCA 652:693 The lectins UEAI, PHA-E, GSI, PNA, and RCA identified remarkable disease-associated differences in glycoprotein expression. 25587705 6 61 dep lectins 656:662 arg1 UEAI 664:667 UEAI 664:667 UEAI 664:667 The lectins UEAI, PHA-E, GSI, PNA, and RCA identified remarkable disease-associated differences in glycoprotein expression. 25587705 6 61 dep lectins 656:662 arg1 PNA 682:684 PNA 682:684 PNA 682:684 The lectins UEAI, PHA-E, GSI, PNA, and RCA identified remarkable disease-associated differences in glycoprotein expression. 25587705 10 62 theme protein 1302:1308 arg1 analysis 1324:1331 protein glycosylation analysis 1302:1331 protein glycosylation analysis 1302:1331 Thus, our study demonstrates the unexplored potential of protein glycosylation analysis in the discovery of molecules linked to diabetic kidney disease. 25587705 6 63 theme disease-associated 717:734 arg1 differences 736:746 remarkable disease-associated differences 706:746 remarkable disease-associated differences in glycoprotein expression 706:773 The lectins UEAI, PHA-E, GSI, PNA, and RCA identified remarkable disease-associated differences in glycoprotein expression. 25587705 10 64 theme glycosylation 1310:1322 arg1 analysis 1324:1331 protein glycosylation analysis 1302:1331 protein glycosylation analysis 1302:1331 Thus, our study demonstrates the unexplored potential of protein glycosylation analysis in the discovery of molecules linked to diabetic kidney disease. 25587705 2 65 contain have 227:230 arg2 impact 241:246 a direct impact 232:246 a direct impact 232:246 Hyperglycemia per se is expected to have a direct impact on the biosynthesis of N- and O-linked glycoproteins. 25587705 2 65 contain have 227:230 arg1 Hyperglycemia 191:203 Hyperglycemia 191:203 Hyperglycemia per se 191:210 Hyperglycemia per se is expected to have a direct impact on the biosynthesis of N- and O-linked glycoproteins. 25587705 0 66 theme rat 52:54 arg1 nephropathy 65:75 rat diabetic nephropathy 52:75 rat diabetic nephropathy 52:75 Glycosylation patterns of kidney proteins differ in rat diabetic nephropathy. 25587705 2 67 theme direct 234:239 arg1 impact 241:246 a direct impact 232:246 a direct impact 232:246 Hyperglycemia per se is expected to have a direct impact on the biosynthesis of N- and O-linked glycoproteins. 25587705 6 68 theme remarkable 706:715 arg1 differences 736:746 remarkable disease-associated differences 706:746 remarkable disease-associated differences in glycoprotein expression 706:773 The lectins UEAI, PHA-E, GSI, PNA, and RCA identified remarkable disease-associated differences in glycoprotein expression. 26957542 9 0 theme absent 1366:1371 arg1 discs 1391:1395 absent small or homeotic discs 1 1366:1397 absent small or homeotic discs 1 (ASH1) 1366:1404 We found that trithorax (TRX), absent small or homeotic discs 1 (ASH1), and Compass member SET1 histone methyltransferases were O-GlcNAc-modified in oga(del.1) mutants. 26957542 9 0 theme absent 1366:1371 arg1 ASH1 1400:1403 ASH1 1400:1403 ASH1 1400:1403 We found that trithorax (TRX), absent small or homeotic discs 1 (ASH1), and Compass member SET1 histone methyltransferases were O-GlcNAc-modified in oga(del.1) mutants. 26957542 7 1 theme O-GlcNAc 1079:1086 arg1 cycling 1088:1094 altered O-GlcNAc cycling 1071:1094 altered O-GlcNAc cycling 1071:1094 Microarray analysis suggested that altered O-GlcNAc cycling perturbed the expression of genes associated with morphogenesis and cell cycle regulation. 26957542 5 2 theme O-GlcNAc-occupied 791:807 arg1 genes 827:831 genes 827:831 genes linked to cell cycle, ubiquitin, and steroid response 827:885 After OGA RNAi, we observed a genome-wide increase in the intensity of most O-GlcNAc-occupied regions including genes linked to cell cycle, ubiquitin, and steroid response. 26957542 5 2 theme O-GlcNAc-occupied 791:807 arg1 regions 809:815 most O-GlcNAc-occupied regions 786:815 most O-GlcNAc-occupied regions including genes linked to cell cycle, ubiquitin, and steroid response 786:885 After OGA RNAi, we observed a genome-wide increase in the intensity of most O-GlcNAc-occupied regions including genes linked to cell cycle, ubiquitin, and steroid response. 26957542 7 3 theme cell 1164:1167 arg1 regulation 1175:1184 cell cycle regulation 1164:1184 cell cycle regulation 1164:1184 Microarray analysis suggested that altered O-GlcNAc cycling perturbed the expression of genes associated with morphogenesis and cell cycle regulation. 26957542 11 4 theme O-GlcNAc 1706:1713 arg1 accumulation 1715:1726 O-GlcNAc accumulation 1706:1726 O-GlcNAc accumulation 1706:1726 Our results show that the loss of OGA in Drosophila globally impacts the epigenetic machinery allowing O-GlcNAc accumulation on RNA polymerase II and numerous chromatin factors including TRX, ASH1, and SET1. 26957542 4 5 theme microarray 650:659 arg1 analysis 661:668 microarray analysis 650:668 microarray analysis 650:668 To pinpoint genomic regions that are regulated by O-GlcNAc levels, we performed ChIP-chip and microarray analysis after OGT or OGA RNAi knockdown in S2 cells. 26957542 5 6 theme cell 843:846 arg1 cycle 848:852 cell cycle 843:852 cell cycle 843:852 After OGA RNAi, we observed a genome-wide increase in the intensity of most O-GlcNAc-occupied regions including genes linked to cell cycle, ubiquitin, and steroid response. 26957542 8 7 theme null 1213:1216 arg1 allele 1218:1223 a viable null allele 1204:1223 a viable null allele of oga (oga(del.1)) in Drosophila allowing visualization of altered O-GlcNAc cycling on polytene chromosomes 1204:1332 We then produced a viable null allele of oga (oga(del.1)) in Drosophila allowing visualization of altered O-GlcNAc cycling on polytene chromosomes. 26957542 9 8 theme histone 1431:1437 arg1 methyltransferases 1439:1456 SET1 histone methyltransferases 1426:1456 SET1 histone methyltransferases 1426:1456 We found that trithorax (TRX), absent small or homeotic discs 1 (ASH1), and Compass member SET1 histone methyltransferases were O-GlcNAc-modified in oga(del.1) mutants. 26957542 9 9 from mutants 1495:1501 arg1 O-GlcNAc-modified 1463:1479 O-GlcNAc-modified 1463:1479 O-GlcNAc-modified 1463:1479 We found that trithorax (TRX), absent small or homeotic discs 1 (ASH1), and Compass member SET1 histone methyltransferases were O-GlcNAc-modified in oga(del.1) mutants. 26957542 9 10 dep absent 1366:1371 arg1 small 1373:1377 small 1373:1377 small 1373:1377 We found that trithorax (TRX), absent small or homeotic discs 1 (ASH1), and Compass member SET1 histone methyltransferases were O-GlcNAc-modified in oga(del.1) mutants. 26957542 4 11 theme RNAi 687:690 arg1 knockdown 692:700 OGA RNAi knockdown 683:700 OGA RNAi knockdown 683:700 To pinpoint genomic regions that are regulated by O-GlcNAc levels, we performed ChIP-chip and microarray analysis after OGT or OGA RNAi knockdown in S2 cells. 26957542 5 12 theme steroid 870:876 arg1 response 878:885 steroid response 870:885 steroid response 870:885 After OGA RNAi, we observed a genome-wide increase in the intensity of most O-GlcNAc-occupied regions including genes linked to cell cycle, ubiquitin, and steroid response. 26957542 8 13 theme O-GlcNAc 1293:1300 arg1 cycling 1302:1308 altered O-GlcNAc cycling 1285:1308 altered O-GlcNAc cycling on polytene chromosomes 1285:1332 We then produced a viable null allele of oga (oga(del.1)) in Drosophila allowing visualization of altered O-GlcNAc cycling on polytene chromosomes. 26957542 6 14 theme polycomb 969:976 arg1 repression 978:987 polycomb repression 969:987 polycomb repression 969:987 In contrast, O-GlcNAc levels were strikingly insensitive to OGA RNAi at sites of polycomb repression such as the Hox and NK homeobox gene clusters. 26957542 1 15 theme Drosophila 100:109 arg1 development 111:121 Drosophila development 100:121 Drosophila development 100:121 Gene expression during Drosophila development is subject to regulation by the Polycomb (Pc), Trithorax (Trx), and Compass chromatin modifier complexes. 26957542 10 16 theme distinct 1561:1568 arg1 set 1570:1572 a distinct set 1559:1572 a distinct set of cell cycle-related genes 1559:1600 The oga(del.1) mutants displayed altered expression of a distinct set of cell cycle-related genes. 26957542 10 16 theme distinct 1561:1568 arg1 genes 1596:1600 cell cycle-related genes 1577:1600 cell cycle-related genes 1577:1600 The oga(del.1) mutants displayed altered expression of a distinct set of cell cycle-related genes. 26957542 0 17 theme Drosophila 0:9 arg1 Deletion 23:30 Drosophila O-GlcNAcase Deletion 0:30 Drosophila O-GlcNAcase Deletion 0:30 Drosophila O-GlcNAcase Deletion Globally Perturbs Chromatin O-GlcNAcylation. 26957542 6 18 theme homeobox 1012:1019 arg1 clusters 1026:1033 the Hox and NK homeobox gene clusters 997:1033 clusters 1026:1033 In contrast, O-GlcNAc levels were strikingly insensitive to OGA RNAi at sites of polycomb repression such as the Hox and NK homeobox gene clusters. 26957542 4 19 theme genomic 568:574 arg1 regions 576:582 genomic regions 568:582 genomic regions that are regulated by O-GlcNAc levels 568:620 To pinpoint genomic regions that are regulated by O-GlcNAc levels, we performed ChIP-chip and microarray analysis after OGT or OGA RNAi knockdown in S2 cells. 26957542 7 20 theme cycle 1169:1173 arg1 regulation 1175:1184 cell cycle regulation 1164:1184 cell cycle regulation 1164:1184 Microarray analysis suggested that altered O-GlcNAc cycling perturbed the expression of genes associated with morphogenesis and cell cycle regulation. 26957542 10 21 theme cycle-related 1582:1594 arg1 genes 1596:1600 cell cycle-related genes 1577:1600 cell cycle-related genes 1577:1600 The oga(del.1) mutants displayed altered expression of a distinct set of cell cycle-related genes. 26957542 3 22 theme regulators 500:509 arg1 regulators 500:509 key transcriptional regulators 480:509 key transcriptional regulators 480:509 OGT transfers O-GlcNAc onto serine and threonine residues in intrinsically disordered domains of key transcriptional regulators; O-GlcNAcase (OGA) removes the modification. 26957542 3 22 theme regulators 500:509 arg1 domains 469:475 intrinsically disordered domains 444:475 intrinsically disordered domains of key transcriptional regulators 444:509 OGT transfers O-GlcNAc onto serine and threonine residues in intrinsically disordered domains of key transcriptional regulators; O-GlcNAcase (OGA) removes the modification. 26957542 7 23 theme genes 1124:1128 arg1 expression 1110:1119 the expression 1106:1119 the expression of genes associated with morphogenesis and cell cycle regulation 1106:1184 Microarray analysis suggested that altered O-GlcNAc cycling perturbed the expression of genes associated with morphogenesis and cell cycle regulation. 26957542 5 24 attach linked 833:838 arg1 response 878:885 steroid response 870:885 steroid response 870:885 After OGA RNAi, we observed a genome-wide increase in the intensity of most O-GlcNAc-occupied regions including genes linked to cell cycle, ubiquitin, and steroid response. 26957542 5 24 attach linked 833:838 arg2 genes 827:831 genes 827:831 genes linked to cell cycle, ubiquitin, and steroid response 827:885 After OGA RNAi, we observed a genome-wide increase in the intensity of most O-GlcNAc-occupied regions including genes linked to cell cycle, ubiquitin, and steroid response. 26957542 5 24 attach linked 833:838 arg1 ubiquitin 855:863 ubiquitin 855:863 ubiquitin 855:863 After OGA RNAi, we observed a genome-wide increase in the intensity of most O-GlcNAc-occupied regions including genes linked to cell cycle, ubiquitin, and steroid response. 26957542 5 24 attach linked 833:838 arg1 cycle 848:852 cell cycle 843:852 cell cycle 843:852 After OGA RNAi, we observed a genome-wide increase in the intensity of most O-GlcNAc-occupied regions including genes linked to cell cycle, ubiquitin, and steroid response. 26957542 6 25 from insensitive 933:943 arg1 contrast 891:898 contrast 891:898 contrast 891:898 In contrast, O-GlcNAc levels were strikingly insensitive to OGA RNAi at sites of polycomb repression such as the Hox and NK homeobox gene clusters. 26957542 11 26 theme OGA 1637:1639 arg1 loss 1629:1632 the loss 1625:1632 the loss of OGA in Drosophila 1625:1653 Our results show that the loss of OGA in Drosophila globally impacts the epigenetic machinery allowing O-GlcNAc accumulation on RNA polymerase II and numerous chromatin factors including TRX, ASH1, and SET1. 26957542 11 27 theme chromatin 1762:1770 arg1 ASH1 1795:1798 ASH1 1795:1798 ASH1 1795:1798 Our results show that the loss of OGA in Drosophila globally impacts the epigenetic machinery allowing O-GlcNAc accumulation on RNA polymerase II and numerous chromatin factors including TRX, ASH1, and SET1. 26957542 11 27 theme chromatin 1762:1770 arg1 SET1 1805:1808 SET1 1805:1808 SET1 1805:1808 Our results show that the loss of OGA in Drosophila globally impacts the epigenetic machinery allowing O-GlcNAc accumulation on RNA polymerase II and numerous chromatin factors including TRX, ASH1, and SET1. 26957542 11 27 theme chromatin 1762:1770 arg1 TRX 1790:1792 TRX 1790:1792 TRX 1790:1792 Our results show that the loss of OGA in Drosophila globally impacts the epigenetic machinery allowing O-GlcNAc accumulation on RNA polymerase II and numerous chromatin factors including TRX, ASH1, and SET1. 26957542 11 27 theme chromatin 1762:1770 arg1 factors 1772:1778 numerous chromatin factors 1753:1778 numerous chromatin factors including TRX, ASH1, and SET1 1753:1808 Our results show that the loss of OGA in Drosophila globally impacts the epigenetic machinery allowing O-GlcNAc accumulation on RNA polymerase II and numerous chromatin factors including TRX, ASH1, and SET1. 26957542 1 28 theme modifier 209:216 arg1 complexes 218:226 Compass chromatin modifier complexes 191:226 Compass chromatin modifier complexes 191:226 Gene expression during Drosophila development is subject to regulation by the Polycomb (Pc), Trithorax (Trx), and Compass chromatin modifier complexes. 26957542 4 29 theme O-GlcNAc 606:613 arg1 levels 615:620 O-GlcNAc levels 606:620 O-GlcNAc levels 606:620 To pinpoint genomic regions that are regulated by O-GlcNAc levels, we performed ChIP-chip and microarray analysis after OGT or OGA RNAi knockdown in S2 cells. 26957542 6 30 from contrast 891:898 arg1 insensitive 933:943 insensitive 933:943 insensitive 933:943 In contrast, O-GlcNAc levels were strikingly insensitive to OGA RNAi at sites of polycomb repression such as the Hox and NK homeobox gene clusters. 26957542 10 31 theme cell 1577:1580 arg1 genes 1596:1600 cell cycle-related genes 1577:1600 cell cycle-related genes 1577:1600 The oga(del.1) mutants displayed altered expression of a distinct set of cell cycle-related genes. 26957542 8 32 from cycling 1302:1308 arg1 chromosomes 1322:1332 polytene chromosomes 1313:1332 polytene chromosomes 1313:1332 We then produced a viable null allele of oga (oga(del.1)) in Drosophila allowing visualization of altered O-GlcNAc cycling on polytene chromosomes. 26957542 6 33 theme O-GlcNAc 901:908 arg1 levels 910:915 O-GlcNAc levels 901:915 O-GlcNAc levels 901:915 In contrast, O-GlcNAc levels were strikingly insensitive to OGA RNAi at sites of polycomb repression such as the Hox and NK homeobox gene clusters. 26957542 2 34 theme key 347:349 arg1 role 351:354 a key role 345:354 a key role 345:354 O-GlcNAc transferase (OGT/SXC) is essential for Pc repression suggesting that the O-GlcNAcylation of proteins plays a key role in regulating development. 26957542 4 35 from knockdown 692:700 arg1 cells 708:712 S2 cells 705:712 S2 cells 705:712 To pinpoint genomic regions that are regulated by O-GlcNAc levels, we performed ChIP-chip and microarray analysis after OGT or OGA RNAi knockdown in S2 cells. 26957542 9 36 from O-GlcNAc-modified 1463:1479 arg1 mutants 1495:1501 oga(del.1) mutants 1484:1501 oga(del.1) mutants 1484:1501 We found that trithorax (TRX), absent small or homeotic discs 1 (ASH1), and Compass member SET1 histone methyltransferases were O-GlcNAc-modified in oga(del.1) mutants. 26957542 10 37 theme oga 1508:1510 arg1 mutants 1519:1525 The oga(del.1) mutants 1504:1525 The oga(del.1) mutants 1504:1525 The oga(del.1) mutants displayed altered expression of a distinct set of cell cycle-related genes. 26957542 2 38 theme Pc 277:278 arg1 repression 280:289 Pc repression 277:289 Pc repression suggesting that the O-GlcNAcylation of proteins plays a key role in regulating development 277:380 O-GlcNAc transferase (OGT/SXC) is essential for Pc repression suggesting that the O-GlcNAcylation of proteins plays a key role in regulating development. 26957542 7 39 theme altered 1071:1077 arg1 cycling 1088:1094 altered O-GlcNAc cycling 1071:1094 altered O-GlcNAc cycling 1071:1094 Microarray analysis suggested that altered O-GlcNAc cycling perturbed the expression of genes associated with morphogenesis and cell cycle regulation. 26957542 4 40 from OGT 676:678 arg1 cells 708:712 S2 cells 705:712 S2 cells 705:712 To pinpoint genomic regions that are regulated by O-GlcNAc levels, we performed ChIP-chip and microarray analysis after OGT or OGA RNAi knockdown in S2 cells. 26957542 9 41 theme homeotic 1382:1389 arg1 discs 1391:1395 absent small or homeotic discs 1 1366:1397 absent small or homeotic discs 1 (ASH1) 1366:1404 We found that trithorax (TRX), absent small or homeotic discs 1 (ASH1), and Compass member SET1 histone methyltransferases were O-GlcNAc-modified in oga(del.1) mutants. 26957542 9 41 theme homeotic 1382:1389 arg1 ASH1 1400:1403 ASH1 1400:1403 ASH1 1400:1403 We found that trithorax (TRX), absent small or homeotic discs 1 (ASH1), and Compass member SET1 histone methyltransferases were O-GlcNAc-modified in oga(del.1) mutants. 26957542 8 42 theme oga 1228:1230 arg1 allele 1218:1223 a viable null allele 1204:1223 a viable null allele of oga (oga(del.1)) in Drosophila allowing visualization of altered O-GlcNAc cycling on polytene chromosomes 1204:1332 We then produced a viable null allele of oga (oga(del.1)) in Drosophila allowing visualization of altered O-GlcNAc cycling on polytene chromosomes. 26957542 11 43 theme RNA 1731:1733 arg1 polymerase 1735:1744 RNA polymerase II 1731:1747 RNA polymerase II 1731:1747 Our results show that the loss of OGA in Drosophila globally impacts the epigenetic machinery allowing O-GlcNAc accumulation on RNA polymerase II and numerous chromatin factors including TRX, ASH1, and SET1. 26957542 7 44 theme Microarray 1036:1045 arg1 analysis 1047:1054 Microarray analysis 1036:1054 Microarray analysis 1036:1054 Microarray analysis suggested that altered O-GlcNAc cycling perturbed the expression of genes associated with morphogenesis and cell cycle regulation. 26957542 6 45 theme OGA 948:950 arg1 RNAi 952:955 OGA RNAi 948:955 OGA RNAi 948:955 In contrast, O-GlcNAc levels were strikingly insensitive to OGA RNAi at sites of polycomb repression such as the Hox and NK homeobox gene clusters. 26957542 2 46 theme O-GlcNAc 229:236 arg1 OGT/SXC 251:257 OGT/SXC 251:257 OGT/SXC 251:257 O-GlcNAc transferase (OGT/SXC) is essential for Pc repression suggesting that the O-GlcNAcylation of proteins plays a key role in regulating development. 26957542 2 46 theme O-GlcNAc 229:236 arg1 transferase 238:248 O-GlcNAc transferase 229:248 O-GlcNAc transferase (OGT/SXC) 229:258 O-GlcNAc transferase (OGT/SXC) is essential for Pc repression suggesting that the O-GlcNAcylation of proteins plays a key role in regulating development. 26957542 1 47 theme Compass 191:197 arg1 complexes 218:226 Compass chromatin modifier complexes 191:226 Compass chromatin modifier complexes 191:226 Gene expression during Drosophila development is subject to regulation by the Polycomb (Pc), Trithorax (Trx), and Compass chromatin modifier complexes. 26957542 9 48 dep trithorax 1349:1357 arg1 methyltransferases 1439:1456 SET1 histone methyltransferases 1426:1456 SET1 histone methyltransferases 1426:1456 We found that trithorax (TRX), absent small or homeotic discs 1 (ASH1), and Compass member SET1 histone methyltransferases were O-GlcNAc-modified in oga(del.1) mutants. 26957542 10 49 theme altered 1537:1543 arg1 expression 1545:1554 altered expression 1537:1554 altered expression of a distinct set of cell cycle-related genes 1537:1600 The oga(del.1) mutants displayed altered expression of a distinct set of cell cycle-related genes. 26957542 11 50 theme numerous 1753:1760 arg1 ASH1 1795:1798 ASH1 1795:1798 ASH1 1795:1798 Our results show that the loss of OGA in Drosophila globally impacts the epigenetic machinery allowing O-GlcNAc accumulation on RNA polymerase II and numerous chromatin factors including TRX, ASH1, and SET1. 26957542 11 50 theme numerous 1753:1760 arg1 SET1 1805:1808 SET1 1805:1808 SET1 1805:1808 Our results show that the loss of OGA in Drosophila globally impacts the epigenetic machinery allowing O-GlcNAc accumulation on RNA polymerase II and numerous chromatin factors including TRX, ASH1, and SET1. 26957542 11 50 theme numerous 1753:1760 arg1 TRX 1790:1792 TRX 1790:1792 TRX 1790:1792 Our results show that the loss of OGA in Drosophila globally impacts the epigenetic machinery allowing O-GlcNAc accumulation on RNA polymerase II and numerous chromatin factors including TRX, ASH1, and SET1. 26957542 11 50 theme numerous 1753:1760 arg1 factors 1772:1778 numerous chromatin factors 1753:1778 numerous chromatin factors including TRX, ASH1, and SET1 1753:1808 Our results show that the loss of OGA in Drosophila globally impacts the epigenetic machinery allowing O-GlcNAc accumulation on RNA polymerase II and numerous chromatin factors including TRX, ASH1, and SET1. 26957542 9 51 theme Compass 1411:1417 arg1 member 1419:1424 Compass member 1411:1424 Compass member 1411:1424 We found that trithorax (TRX), absent small or homeotic discs 1 (ASH1), and Compass member SET1 histone methyltransferases were O-GlcNAc-modified in oga(del.1) mutants. 26957542 8 52 theme viable 1206:1211 arg1 allele 1218:1223 a viable null allele 1204:1223 a viable null allele of oga (oga(del.1)) in Drosophila allowing visualization of altered O-GlcNAc cycling on polytene chromosomes 1204:1332 We then produced a viable null allele of oga (oga(del.1)) in Drosophila allowing visualization of altered O-GlcNAc cycling on polytene chromosomes. 26957542 4 53 theme S2 705:706 arg1 cells 708:712 S2 cells 705:712 S2 cells 705:712 To pinpoint genomic regions that are regulated by O-GlcNAc levels, we performed ChIP-chip and microarray analysis after OGT or OGA RNAi knockdown in S2 cells. 26957542 5 54 from increase 757:764 arg1 intensity 773:781 the intensity 769:781 the intensity of most O-GlcNAc-occupied regions including genes linked to cell cycle, ubiquitin, and steroid response 769:885 After OGA RNAi, we observed a genome-wide increase in the intensity of most O-GlcNAc-occupied regions including genes linked to cell cycle, ubiquitin, and steroid response. 26957542 8 55 from allele 1218:1223 arg1 Drosophila 1248:1257 Drosophila 1248:1257 Drosophila allowing visualization of altered O-GlcNAc cycling on polytene chromosomes 1248:1332 We then produced a viable null allele of oga (oga(del.1)) in Drosophila allowing visualization of altered O-GlcNAc cycling on polytene chromosomes. 26957542 9 56 theme SET1 1426:1429 arg1 methyltransferases 1439:1456 SET1 histone methyltransferases 1426:1456 SET1 histone methyltransferases 1426:1456 We found that trithorax (TRX), absent small or homeotic discs 1 (ASH1), and Compass member SET1 histone methyltransferases were O-GlcNAc-modified in oga(del.1) mutants. 26957542 1 57 theme Gene 77:80 arg1 expression 82:91 Gene expression 77:91 Gene expression during Drosophila development 77:121 Gene expression during Drosophila development is subject to regulation by the Polycomb (Pc), Trithorax (Trx), and Compass chromatin modifier complexes. 26957542 3 58 theme key 480:482 arg1 regulators 500:509 key transcriptional regulators 480:509 key transcriptional regulators 480:509 OGT transfers O-GlcNAc onto serine and threonine residues in intrinsically disordered domains of key transcriptional regulators; O-GlcNAcase (OGA) removes the modification. 26957542 11 59 from loss 1629:1632 arg1 Drosophila 1644:1653 Drosophila 1644:1653 Drosophila 1644:1653 Our results show that the loss of OGA in Drosophila globally impacts the epigenetic machinery allowing O-GlcNAc accumulation on RNA polymerase II and numerous chromatin factors including TRX, ASH1, and SET1. 26957542 4 60 theme OGA 683:685 arg1 knockdown 692:700 OGA RNAi knockdown 683:700 OGA RNAi knockdown 683:700 To pinpoint genomic regions that are regulated by O-GlcNAc levels, we performed ChIP-chip and microarray analysis after OGT or OGA RNAi knockdown in S2 cells. 26957542 5 61 theme genome-wide 745:755 arg1 increase 757:764 a genome-wide increase 743:764 a genome-wide increase in the intensity of most O-GlcNAc-occupied regions including genes linked to cell cycle, ubiquitin, and steroid response 743:885 After OGA RNAi, we observed a genome-wide increase in the intensity of most O-GlcNAc-occupied regions including genes linked to cell cycle, ubiquitin, and steroid response. 26957542 3 62 from O-GlcNAc 397:404 arg1 regulators 500:509 key transcriptional regulators 480:509 key transcriptional regulators 480:509 OGT transfers O-GlcNAc onto serine and threonine residues in intrinsically disordered domains of key transcriptional regulators; O-GlcNAcase (OGA) removes the modification. 26957542 3 62 from O-GlcNAc 397:404 arg1 domains 469:475 intrinsically disordered domains 444:475 intrinsically disordered domains of key transcriptional regulators 444:509 OGT transfers O-GlcNAc onto serine and threonine residues in intrinsically disordered domains of key transcriptional regulators; O-GlcNAcase (OGA) removes the modification. 26957542 6 63 theme repression 978:987 arg1 sites 960:964 sites 960:964 sites of polycomb repression such as the Hox and NK homeobox gene clusters 960:1033 In contrast, O-GlcNAc levels were strikingly insensitive to OGA RNAi at sites of polycomb repression such as the Hox and NK homeobox gene clusters. 26957542 6 63 theme repression 978:987 arg1 repression 978:987 polycomb repression 969:987 polycomb repression 969:987 In contrast, O-GlcNAc levels were strikingly insensitive to OGA RNAi at sites of polycomb repression such as the Hox and NK homeobox gene clusters. 26957542 6 63 theme repression 978:987 arg1 clusters 1026:1033 the Hox and NK homeobox gene clusters 997:1033 clusters 1026:1033 In contrast, O-GlcNAc levels were strikingly insensitive to OGA RNAi at sites of polycomb repression such as the Hox and NK homeobox gene clusters. 26957542 6 63 theme repression 978:987 arg1 Hox 1001:1003 the Hox and NK homeobox gene clusters 997:1033 Hox 1001:1003 In contrast, O-GlcNAc levels were strikingly insensitive to OGA RNAi at sites of polycomb repression such as the Hox and NK homeobox gene clusters. 26957542 8 64 theme altered 1285:1291 arg1 cycling 1302:1308 altered O-GlcNAc cycling 1285:1308 altered O-GlcNAc cycling on polytene chromosomes 1285:1332 We then produced a viable null allele of oga (oga(del.1)) in Drosophila allowing visualization of altered O-GlcNAc cycling on polytene chromosomes. 26957542 5 65 theme OGA 721:723 arg1 RNAi 725:728 OGA RNAi 721:728 OGA RNAi 721:728 After OGA RNAi, we observed a genome-wide increase in the intensity of most O-GlcNAc-occupied regions including genes linked to cell cycle, ubiquitin, and steroid response. 26957542 9 66 theme oga 1484:1486 arg1 mutants 1495:1501 oga(del.1) mutants 1484:1501 oga(del.1) mutants 1484:1501 We found that trithorax (TRX), absent small or homeotic discs 1 (ASH1), and Compass member SET1 histone methyltransferases were O-GlcNAc-modified in oga(del.1) mutants. 26957542 8 67 theme cycling 1302:1308 arg1 visualization 1268:1280 visualization 1268:1280 visualization of altered O-GlcNAc cycling on polytene chromosomes 1268:1332 We then produced a viable null allele of oga (oga(del.1)) in Drosophila allowing visualization of altered O-GlcNAc cycling on polytene chromosomes. 26957542 11 68 theme epigenetic 1676:1685 arg1 machinery 1687:1695 the epigenetic machinery 1672:1695 the epigenetic machinery allowing O-GlcNAc accumulation on RNA polymerase II and numerous chromatin factors including TRX, ASH1, and SET1 1672:1808 Our results show that the loss of OGA in Drosophila globally impacts the epigenetic machinery allowing O-GlcNAc accumulation on RNA polymerase II and numerous chromatin factors including TRX, ASH1, and SET1. 26957542 9 69 theme del.1 1488:1492 arg1 mutants 1495:1501 oga(del.1) mutants 1484:1501 oga(del.1) mutants 1484:1501 We found that trithorax (TRX), absent small or homeotic discs 1 (ASH1), and Compass member SET1 histone methyltransferases were O-GlcNAc-modified in oga(del.1) mutants. 26957542 6 70 from sites 960:964 arg1 insensitive 933:943 insensitive 933:943 insensitive 933:943 In contrast, O-GlcNAc levels were strikingly insensitive to OGA RNAi at sites of polycomb repression such as the Hox and NK homeobox gene clusters. 26957542 8 71 theme polytene 1313:1320 arg1 chromosomes 1322:1332 polytene chromosomes 1313:1332 polytene chromosomes 1313:1332 We then produced a viable null allele of oga (oga(del.1)) in Drosophila allowing visualization of altered O-GlcNAc cycling on polytene chromosomes. 26957542 10 72 theme set 1570:1572 arg1 expression 1545:1554 altered expression 1537:1554 altered expression of a distinct set of cell cycle-related genes 1537:1600 The oga(del.1) mutants displayed altered expression of a distinct set of cell cycle-related genes. 26957542 5 73 theme most 786:789 arg1 genes 827:831 genes 827:831 genes linked to cell cycle, ubiquitin, and steroid response 827:885 After OGA RNAi, we observed a genome-wide increase in the intensity of most O-GlcNAc-occupied regions including genes linked to cell cycle, ubiquitin, and steroid response. 26957542 5 73 theme most 786:789 arg1 regions 809:815 most O-GlcNAc-occupied regions 786:815 most O-GlcNAc-occupied regions including genes linked to cell cycle, ubiquitin, and steroid response 786:885 After OGA RNAi, we observed a genome-wide increase in the intensity of most O-GlcNAc-occupied regions including genes linked to cell cycle, ubiquitin, and steroid response. 26957542 3 74 dep serine 411:416 arg1 residues 432:439 residues 432:439 residues 432:439 OGT transfers O-GlcNAc onto serine and threonine residues in intrinsically disordered domains of key transcriptional regulators; O-GlcNAcase (OGA) removes the modification. 26957542 5 75 theme regions 809:815 arg1 intensity 773:781 the intensity 769:781 the intensity of most O-GlcNAc-occupied regions including genes linked to cell cycle, ubiquitin, and steroid response 769:885 After OGA RNAi, we observed a genome-wide increase in the intensity of most O-GlcNAc-occupied regions including genes linked to cell cycle, ubiquitin, and steroid response. 26957542 8 76 from visualization 1268:1280 arg1 chromosomes 1322:1332 polytene chromosomes 1313:1332 polytene chromosomes 1313:1332 We then produced a viable null allele of oga (oga(del.1)) in Drosophila allowing visualization of altered O-GlcNAc cycling on polytene chromosomes. 26957542 6 77 theme gene 1021:1024 arg1 clusters 1026:1033 the Hox and NK homeobox gene clusters 997:1033 clusters 1026:1033 In contrast, O-GlcNAc levels were strikingly insensitive to OGA RNAi at sites of polycomb repression such as the Hox and NK homeobox gene clusters. 26957542 10 78 theme genes 1596:1600 arg1 set 1570:1572 a distinct set 1559:1572 a distinct set of cell cycle-related genes 1559:1600 The oga(del.1) mutants displayed altered expression of a distinct set of cell cycle-related genes. 26957542 10 78 theme genes 1596:1600 arg1 genes 1596:1600 cell cycle-related genes 1577:1600 cell cycle-related genes 1577:1600 The oga(del.1) mutants displayed altered expression of a distinct set of cell cycle-related genes. 26957542 0 79 theme Chromatin 50:58 arg1 O-GlcNAcylation 60:74 Chromatin O-GlcNAcylation 50:74 Chromatin O-GlcNAcylation 50:74 Drosophila O-GlcNAcase Deletion Globally Perturbs Chromatin O-GlcNAcylation. 26957542 6 80 theme NK 1009:1010 arg1 clusters 1026:1033 the Hox and NK homeobox gene clusters 997:1033 clusters 1026:1033 In contrast, O-GlcNAc levels were strikingly insensitive to OGA RNAi at sites of polycomb repression such as the Hox and NK homeobox gene clusters. 26957542 3 81 theme disordered 458:467 arg1 regulators 500:509 key transcriptional regulators 480:509 key transcriptional regulators 480:509 OGT transfers O-GlcNAc onto serine and threonine residues in intrinsically disordered domains of key transcriptional regulators; O-GlcNAcase (OGA) removes the modification. 26957542 3 81 theme disordered 458:467 arg1 domains 469:475 intrinsically disordered domains 444:475 intrinsically disordered domains of key transcriptional regulators 444:509 OGT transfers O-GlcNAc onto serine and threonine residues in intrinsically disordered domains of key transcriptional regulators; O-GlcNAcase (OGA) removes the modification. 26957542 2 82 theme proteins 330:337 arg1 O-GlcNAcylation 311:325 the O-GlcNAcylation 307:325 the O-GlcNAcylation of proteins 307:337 O-GlcNAc transferase (OGT/SXC) is essential for Pc repression suggesting that the O-GlcNAcylation of proteins plays a key role in regulating development. 26957542 8 83 from chromosomes 1322:1332 arg1 visualization 1268:1280 visualization 1268:1280 visualization of altered O-GlcNAc cycling on polytene chromosomes 1268:1332 We then produced a viable null allele of oga (oga(del.1)) in Drosophila allowing visualization of altered O-GlcNAc cycling on polytene chromosomes. 26957542 3 84 theme transcriptional 484:498 arg1 regulators 500:509 key transcriptional regulators 480:509 key transcriptional regulators 480:509 OGT transfers O-GlcNAc onto serine and threonine residues in intrinsically disordered domains of key transcriptional regulators; O-GlcNAcase (OGA) removes the modification. 26957542 1 85 theme chromatin 199:207 arg1 complexes 218:226 Compass chromatin modifier complexes 191:226 Compass chromatin modifier complexes 191:226 Gene expression during Drosophila development is subject to regulation by the Polycomb (Pc), Trithorax (Trx), and Compass chromatin modifier complexes. 26957542 0 86 theme O-GlcNAcase 11:21 arg1 Deletion 23:30 Drosophila O-GlcNAcase Deletion 0:30 Drosophila O-GlcNAcase Deletion 0:30 Drosophila O-GlcNAcase Deletion Globally Perturbs Chromatin O-GlcNAcylation. 27249778 4 0 theme significant 548:558 arg1 redshift 560:567 The significant redshift 544:567 The significant redshift 544:567 The significant redshift of the emission, as compared to the corrole congener, is originated from the ligand-centered triplet character. 27249778 0 1 theme Axial 91:95 arg1 Ligands 97:103 Pyridine-based Axial Ligands 76:103 Pyridine-based Axial Ligands 76:103 Near-Infrared Phosphorescent Iridium(III) Benzonorrole Complexes Possessing Pyridine-based Axial Ligands. 27249778 5 2 theme photophysical 704:716 arg1 properties 718:727 the photophysical properties 700:727 the photophysical properties of the complexes 700:744 The fine-tuning of the photophysical properties of the complexes was achieved by introducing electron-donating and electron-withdrawing substituents on the axial pyridine ligands. 27249778 1 3 theme benzo-annulated 173:187 arg1 analogue 206:213 benzo-annulated N-linked corrole analogue 173:213 benzo-annulated N-linked corrole analogue (termed as benzonorrole) 173:238 Novel near-infrared phosphorescent iridium(III) complexes based on benzo-annulated N-linked corrole analogue (termed as benzonorrole) were synthesized. 27249778 5 4 theme electron-withdrawing 796:815 arg1 substituents 817:828 electron-withdrawing substituents 796:828 electron-withdrawing substituents 796:828 The fine-tuning of the photophysical properties of the complexes was achieved by introducing electron-donating and electron-withdrawing substituents on the axial pyridine ligands. 27249778 2 5 theme axial 400:404 arg1 ligands 406:412 two external axial ligands 387:412 two external axial ligands 387:412 The structures of the complexes revealed octahedral coordination geometries involving an organometallic iridium-carbon bond with two external axial ligands. 27249778 1 6 theme phosphorescent 126:139 arg1 complexes 154:162 Novel near-infrared phosphorescent iridium(III) complexes 106:162 Novel near-infrared phosphorescent iridium(III) complexes based on benzo-annulated N-linked corrole analogue (termed as benzonorrole) 106:238 Novel near-infrared phosphorescent iridium(III) complexes based on benzo-annulated N-linked corrole analogue (termed as benzonorrole) were synthesized. 27249778 2 7 theme coordination 310:321 arg1 geometries 323:332 octahedral coordination geometries 299:332 octahedral coordination geometries involving an organometallic iridium-carbon bond with two external axial ligands 299:412 The structures of the complexes revealed octahedral coordination geometries involving an organometallic iridium-carbon bond with two external axial ligands. 27249778 1 8 theme iridium 141:147 arg1 complexes 154:162 Novel near-infrared phosphorescent iridium(III) complexes 106:162 Novel near-infrared phosphorescent iridium(III) complexes based on benzo-annulated N-linked corrole analogue (termed as benzonorrole) 106:238 Novel near-infrared phosphorescent iridium(III) complexes based on benzo-annulated N-linked corrole analogue (termed as benzonorrole) were synthesized. 27249778 2 9 theme octahedral 299:308 arg1 geometries 323:332 octahedral coordination geometries 299:332 octahedral coordination geometries involving an organometallic iridium-carbon bond with two external axial ligands 299:412 The structures of the complexes revealed octahedral coordination geometries involving an organometallic iridium-carbon bond with two external axial ligands. 27249778 1 10 theme N-linked 189:196 arg1 analogue 206:213 benzo-annulated N-linked corrole analogue 173:213 benzo-annulated N-linked corrole analogue (termed as benzonorrole) 173:238 Novel near-infrared phosphorescent iridium(III) complexes based on benzo-annulated N-linked corrole analogue (termed as benzonorrole) were synthesized. 27249778 1 11 theme corrole 198:204 arg1 analogue 206:213 benzo-annulated N-linked corrole analogue 173:213 benzo-annulated N-linked corrole analogue (termed as benzonorrole) 173:238 Novel near-infrared phosphorescent iridium(III) complexes based on benzo-annulated N-linked corrole analogue (termed as benzonorrole) were synthesized. 27249778 0 12 theme Phosphorescent 14:27 arg1 Iridium 29:35 Near-Infrared Phosphorescent Iridium 0:35 Near-Infrared Phosphorescent Iridium 0:35 Near-Infrared Phosphorescent Iridium(III) Benzonorrole Complexes Possessing Pyridine-based Axial Ligands. 27249778 1 13 link N-linked 189:196 arg1 analogue 206:213 benzo-annulated N-linked corrole analogue 173:213 benzo-annulated N-linked corrole analogue (termed as benzonorrole) 173:238 Novel near-infrared phosphorescent iridium(III) complexes based on benzo-annulated N-linked corrole analogue (termed as benzonorrole) were synthesized. 27249778 5 14 theme axial 837:841 arg1 ligands 852:858 the axial pyridine ligands 833:858 the axial pyridine ligands 833:858 The fine-tuning of the photophysical properties of the complexes was achieved by introducing electron-donating and electron-withdrawing substituents on the axial pyridine ligands. 27249778 2 15 theme iridium-carbon 362:375 arg1 bond 377:380 an organometallic iridium-carbon bond 344:380 an organometallic iridium-carbon bond with two external axial ligands 344:412 The structures of the complexes revealed octahedral coordination geometries involving an organometallic iridium-carbon bond with two external axial ligands. 27249778 3 16 theme near-infrared 464:476 arg1 phosphorescence 478:492 near-infrared phosphorescence 464:492 near-infrared phosphorescence 464:492 Interestingly, the iridium(III) complex exhibits near-infrared phosphorescence at room temperature at wavelengths beyond 900 nm. 27249778 0 17 theme Near-Infrared 0:12 arg1 Iridium 29:35 Near-Infrared Phosphorescent Iridium 0:35 Near-Infrared Phosphorescent Iridium 0:35 Near-Infrared Phosphorescent Iridium(III) Benzonorrole Complexes Possessing Pyridine-based Axial Ligands. 27249778 1 18 theme Novel 106:110 arg1 complexes 154:162 Novel near-infrared phosphorescent iridium(III) complexes 106:162 Novel near-infrared phosphorescent iridium(III) complexes based on benzo-annulated N-linked corrole analogue (termed as benzonorrole) 106:238 Novel near-infrared phosphorescent iridium(III) complexes based on benzo-annulated N-linked corrole analogue (termed as benzonorrole) were synthesized. 27249778 1 19 theme near-infrared 112:124 arg1 complexes 154:162 Novel near-infrared phosphorescent iridium(III) complexes 106:162 Novel near-infrared phosphorescent iridium(III) complexes based on benzo-annulated N-linked corrole analogue (termed as benzonorrole) 106:238 Novel near-infrared phosphorescent iridium(III) complexes based on benzo-annulated N-linked corrole analogue (termed as benzonorrole) were synthesized. 27249778 2 20 theme organometallic 347:360 arg1 bond 377:380 an organometallic iridium-carbon bond 344:380 an organometallic iridium-carbon bond with two external axial ligands 344:412 The structures of the complexes revealed octahedral coordination geometries involving an organometallic iridium-carbon bond with two external axial ligands. 27249778 0 21 dep Possessing 65:74 arg1 III 37:39 III 37:39 III 37:39 Near-Infrared Phosphorescent Iridium(III) Benzonorrole Complexes Possessing Pyridine-based Axial Ligands. 27249778 4 22 theme corrole 605:611 arg1 congener 613:620 the corrole congener 601:620 the corrole congener 601:620 The significant redshift of the emission, as compared to the corrole congener, is originated from the ligand-centered triplet character. 27249778 2 23 with bond 377:380 arg1 ligands 406:412 two external axial ligands 387:412 two external axial ligands 387:412 The structures of the complexes revealed octahedral coordination geometries involving an organometallic iridium-carbon bond with two external axial ligands. 27249778 1 24 dep analogue 206:213 arg1 termed 216:221 termed 216:221 termed as benzonorrole 216:237 Novel near-infrared phosphorescent iridium(III) complexes based on benzo-annulated N-linked corrole analogue (termed as benzonorrole) were synthesized. 27249778 4 25 theme emission 576:583 arg1 redshift 560:567 The significant redshift 544:567 The significant redshift 544:567 The significant redshift of the emission, as compared to the corrole congener, is originated from the ligand-centered triplet character. 27249778 2 26 theme external 391:398 arg1 ligands 406:412 two external axial ligands 387:412 two external axial ligands 387:412 The structures of the complexes revealed octahedral coordination geometries involving an organometallic iridium-carbon bond with two external axial ligands. 27249778 0 27 theme Benzonorrole 42:53 arg1 Complexes 55:63 Benzonorrole Complexes 42:63 Benzonorrole Complexes 42:63 Near-Infrared Phosphorescent Iridium(III) Benzonorrole Complexes Possessing Pyridine-based Axial Ligands. 27249778 4 28 dep redshift 560:567 arg1 compared 589:596 compared 589:596 compared to the corrole congener 589:620 The significant redshift of the emission, as compared to the corrole congener, is originated from the ligand-centered triplet character. 27249778 5 29 theme complexes 736:744 arg1 properties 718:727 the photophysical properties 700:727 the photophysical properties of the complexes 700:744 The fine-tuning of the photophysical properties of the complexes was achieved by introducing electron-donating and electron-withdrawing substituents on the axial pyridine ligands. 27249778 5 30 theme properties 718:727 arg1 fine-tuning 685:695 The fine-tuning 681:695 The fine-tuning of the photophysical properties of the complexes 681:744 The fine-tuning of the photophysical properties of the complexes was achieved by introducing electron-donating and electron-withdrawing substituents on the axial pyridine ligands. 27249778 2 31 theme complexes 280:288 arg1 structures 262:271 The structures 258:271 The structures of the complexes 258:288 The structures of the complexes revealed octahedral coordination geometries involving an organometallic iridium-carbon bond with two external axial ligands. 27249778 4 32 theme ligand-centered 646:660 arg1 character 670:678 the ligand-centered triplet character 642:678 the ligand-centered triplet character 642:678 The significant redshift of the emission, as compared to the corrole congener, is originated from the ligand-centered triplet character. 27249778 0 33 theme Pyridine-based 76:89 arg1 Ligands 97:103 Pyridine-based Axial Ligands 76:103 Pyridine-based Axial Ligands 76:103 Near-Infrared Phosphorescent Iridium(III) Benzonorrole Complexes Possessing Pyridine-based Axial Ligands. 27249778 3 34 theme room 497:500 arg1 temperature 502:512 room temperature 497:512 room temperature 497:512 Interestingly, the iridium(III) complex exhibits near-infrared phosphorescence at room temperature at wavelengths beyond 900 nm. 27249778 5 35 theme pyridine 843:850 arg1 ligands 852:858 the axial pyridine ligands 833:858 the axial pyridine ligands 833:858 The fine-tuning of the photophysical properties of the complexes was achieved by introducing electron-donating and electron-withdrawing substituents on the axial pyridine ligands. 27249778 3 36 theme iridium 434:440 arg1 complex 447:453 the iridium(III) complex 430:453 the iridium(III) complex 430:453 Interestingly, the iridium(III) complex exhibits near-infrared phosphorescence at room temperature at wavelengths beyond 900 nm. 27249778 4 37 theme triplet 662:668 arg1 character 670:678 the ligand-centered triplet character 642:678 the ligand-centered triplet character 642:678 The significant redshift of the emission, as compared to the corrole congener, is originated from the ligand-centered triplet character. 27486479 3 0 theme cell 511:514 arg1 walls 516:520 the plant cell walls 501:520 the plant cell walls of lignocellulose 501:538 Certain ionic liquids (ILs) are very effective at disrupting the plant cell walls of lignocellulose, and generate a substrate that is effectively hydrolyzed into fermentable sugars. 27486479 10 1 theme [OH 2207:2209 arg1 IL 2212:2213 [TBA][OH] IL 2202:2213 [TBA][OH] IL 2202:2213 [TBA][OH] IL is more reactive in terms of ionic mobility which extends removal of lignin and noncellulosic components of biomass at the lower temperature pretreatment. 27486479 7 2 theme profiling 1425:1433 arg1 experiments 1435:1445 Glycome profiling experiments 1417:1445 Glycome profiling experiments 1417:1445 Glycome profiling experiments and computational results indicate that removal of the noncellulosic polysaccharides occurs due to the ionic mobility of [TBA][OH] and is the key factor in determining pretreatment efficiency. 27486479 8 3 theme Process 1640:1646 arg1 modeling 1648:1655 Process modeling 1640:1655 Process modeling 1640:1655 Process modeling and energy demand analysis suggests that this [TBA][OH] pretreatment could potentially reduce the energy required in the pretreatment unit operation by more than 75 %. 27486479 6 4 theme chemical 1241:1248 arg1 composition 1250:1260 chemical composition 1241:1260 chemical composition 1241:1260 The efficiency of [TBA][OH] pretreatment of lignocellulose was further studied by analyzing chemical composition, powder X-ray diffraction for cellulose structure, NMR and SEC for lignin dissolution/depolymerization, and glycome profiling for cell wall modifications. 27486479 1 5 theme fuels 278:282 arg1 production 238:247 the production 234:247 the production of chemicals, materials, and fuels from alternative renewable sources 234:317 BACKGROUND Concerns around greenhouse gas emissions necessitate the development of sustainable processes for the production of chemicals, materials, and fuels from alternative renewable sources. 27486479 1 6 from sources 311:317 arg1 production 238:247 the production 234:247 the production of chemicals, materials, and fuels from alternative renewable sources 234:317 BACKGROUND Concerns around greenhouse gas emissions necessitate the development of sustainable processes for the production of chemicals, materials, and fuels from alternative renewable sources. 27486479 7 7 theme computational 1451:1463 arg1 results 1465:1471 computational results 1451:1471 computational results 1451:1471 Glycome profiling experiments and computational results indicate that removal of the noncellulosic polysaccharides occurs due to the ionic mobility of [TBA][OH] and is the key factor in determining pretreatment efficiency. 27486479 9 8 theme processing 1903:1912 arg1 conditions 1914:1923 very mild processing conditions 1893:1923 very mild processing conditions 1893:1923 CONCLUSIONS By leveraging the benefits of ILs that are effective at very mild processing conditions, such as [TBA][OH], lignocellulosic biomass can be pretreated at similar efficiency as top performing conventional ILs, such as 1-ethyl-3-methylimidazolium acetate [C2C1Im][OAc], but at much lower temperatures, and with less than half the IL normally required to be effective. 27486479 4 9 theme price 685:689 arg1 terms 667:671 terms 667:671 terms of purchase price 667:689 Conventional ILs are relatively expensive in terms of purchase price, and the most effective imidazolium-based ILs also require energy intensive processing conditions (>140 °C, 3 h) to release >90 % fermentable sugar yields after saccharification. 27486479 2 10 theme lignocellulosic 324:338 arg1 sources 386:392 the most abundant sources 368:392 the most abundant sources of carbon for renewable bioenergy production 368:437 The lignocellulosic plant cell walls are one of the most abundant sources of carbon for renewable bioenergy production. 27486479 2 10 theme lignocellulosic 324:338 arg1 one 361:363 one 361:363 one 361:363 The lignocellulosic plant cell walls are one of the most abundant sources of carbon for renewable bioenergy production. 27486479 2 10 theme lignocellulosic 324:338 arg1 walls 351:355 The lignocellulosic plant cell walls 320:355 The lignocellulosic plant cell walls 320:355 The lignocellulosic plant cell walls are one of the most abundant sources of carbon for renewable bioenergy production. 27486479 11 11 from transformative 2439:2452 arg1 affordability 2461:2473 affordability 2461:2473 affordability 2461:2473 This approach to biomass pretreatment at lower temperatures could be transformative in the affordability and energy efficiency of lignocellulosic biorefineries. 27486479 11 11 from transformative 2439:2452 arg1 efficiency 2486:2495 energy efficiency 2479:2495 energy efficiency 2479:2495 This approach to biomass pretreatment at lower temperatures could be transformative in the affordability and energy efficiency of lignocellulosic biorefineries. 27486479 10 12 theme mobility 2250:2257 arg1 terms 2235:2239 terms 2235:2239 terms of ionic mobility which extends removal of lignin and noncellulosic components of biomass at the lower temperature pretreatment 2235:2367 [TBA][OH] IL is more reactive in terms of ionic mobility which extends removal of lignin and noncellulosic components of biomass at the lower temperature pretreatment. 27486479 5 13 theme glucose 1063:1069 arg1 yields 1071:1076 high glucose yields 1058:1076 high glucose yields (~95 %) 1058:1084 RESULTS We have developed a highly effective pretreatment technology utilizing the relatively inexpensive IL comprised tetrabutylammonium [TBA](+) and hydroxide [OH](-) ions that generate high glucose yields (~95 %) after pretreatment at very mild processing conditions (50 °C). 27486479 5 13 theme glucose 1063:1069 arg1 % 1083:1083 ~95 % 1079:1083 ~95 % 1079:1083 RESULTS We have developed a highly effective pretreatment technology utilizing the relatively inexpensive IL comprised tetrabutylammonium [TBA](+) and hydroxide [OH](-) ions that generate high glucose yields (~95 %) after pretreatment at very mild processing conditions (50 °C). 27486479 1 14 theme processes 220:228 arg1 development 193:203 the development 189:203 the development of sustainable processes for the production of chemicals, materials, and fuels from alternative renewable sources 189:317 BACKGROUND Concerns around greenhouse gas emissions necessitate the development of sustainable processes for the production of chemicals, materials, and fuels from alternative renewable sources. 27486479 10 15 dep [OH 2207:2209 arg1 [TBA 2202:2205 [TBA 2202:2205 [TBA 2202:2205 [TBA][OH] IL is more reactive in terms of ionic mobility which extends removal of lignin and noncellulosic components of biomass at the lower temperature pretreatment. 27486479 11 16 theme energy 2479:2484 arg1 efficiency 2486:2495 energy efficiency 2479:2495 energy efficiency 2479:2495 This approach to biomass pretreatment at lower temperatures could be transformative in the affordability and energy efficiency of lignocellulosic biorefineries. 27486479 3 17 theme ionic 448:452 arg1 liquids 454:460 Certain ionic liquids 440:460 Certain ionic liquids (ILs) 440:466 Certain ionic liquids (ILs) are very effective at disrupting the plant cell walls of lignocellulose, and generate a substrate that is effectively hydrolyzed into fermentable sugars. 27486479 3 17 theme ionic 448:452 arg1 ILs 463:465 ILs 463:465 ILs 463:465 Certain ionic liquids (ILs) are very effective at disrupting the plant cell walls of lignocellulose, and generate a substrate that is effectively hydrolyzed into fermentable sugars. 27486479 3 18 theme fermentable 602:612 arg1 sugars 614:619 fermentable sugars 602:619 fermentable sugars 602:619 Certain ionic liquids (ILs) are very effective at disrupting the plant cell walls of lignocellulose, and generate a substrate that is effectively hydrolyzed into fermentable sugars. 27486479 9 19 from conditions 1914:1923 arg1 effective 1880:1888 effective 1880:1888 effective 1880:1888 CONCLUSIONS By leveraging the benefits of ILs that are effective at very mild processing conditions, such as [TBA][OH], lignocellulosic biomass can be pretreated at similar efficiency as top performing conventional ILs, such as 1-ethyl-3-methylimidazolium acetate [C2C1Im][OAc], but at much lower temperatures, and with less than half the IL normally required to be effective. 27486479 4 20 theme imidazolium-based 715:731 arg1 ILs 733:735 the most effective imidazolium-based ILs 696:735 the most effective imidazolium-based ILs 696:735 Conventional ILs are relatively expensive in terms of purchase price, and the most effective imidazolium-based ILs also require energy intensive processing conditions (>140 °C, 3 h) to release >90 % fermentable sugar yields after saccharification. 27486479 11 21 theme biorefineries 2516:2528 arg1 affordability 2461:2473 affordability 2461:2473 affordability 2461:2473 This approach to biomass pretreatment at lower temperatures could be transformative in the affordability and energy efficiency of lignocellulosic biorefineries. 27486479 11 21 theme biorefineries 2516:2528 arg1 efficiency 2486:2495 energy efficiency 2479:2495 energy efficiency 2479:2495 This approach to biomass pretreatment at lower temperatures could be transformative in the affordability and energy efficiency of lignocellulosic biorefineries. 27486479 6 22 theme X-ray 1270:1274 arg1 diffraction 1276:1286 powder X-ray diffraction 1263:1286 powder X-ray diffraction for cellulose structure 1263:1310 The efficiency of [TBA][OH] pretreatment of lignocellulose was further studied by analyzing chemical composition, powder X-ray diffraction for cellulose structure, NMR and SEC for lignin dissolution/depolymerization, and glycome profiling for cell wall modifications. 27486479 8 23 theme pretreatment 1778:1789 arg1 operation 1796:1804 the pretreatment unit operation 1774:1804 the pretreatment unit operation 1774:1804 Process modeling and energy demand analysis suggests that this [TBA][OH] pretreatment could potentially reduce the energy required in the pretreatment unit operation by more than 75 %. 27486479 11 24 dep affordability 2461:2473 arg1 the 2457:2459 the 2457:2459 the 2457:2459 This approach to biomass pretreatment at lower temperatures could be transformative in the affordability and energy efficiency of lignocellulosic biorefineries. 27486479 10 25 theme components 2309:2318 arg1 removal 2273:2279 removal 2273:2279 removal of lignin and noncellulosic components of biomass 2273:2329 [TBA][OH] IL is more reactive in terms of ionic mobility which extends removal of lignin and noncellulosic components of biomass at the lower temperature pretreatment. 27486479 9 26 theme lignocellulosic 1945:1959 arg1 biomass 1961:1967 lignocellulosic biomass 1945:1967 lignocellulosic biomass 1945:1967 CONCLUSIONS By leveraging the benefits of ILs that are effective at very mild processing conditions, such as [TBA][OH], lignocellulosic biomass can be pretreated at similar efficiency as top performing conventional ILs, such as 1-ethyl-3-methylimidazolium acetate [C2C1Im][OAc], but at much lower temperatures, and with less than half the IL normally required to be effective. 27486479 6 27 theme glycome 1370:1376 arg1 profiling 1378:1386 glycome profiling 1370:1386 glycome profiling for cell wall modifications 1370:1414 The efficiency of [TBA][OH] pretreatment of lignocellulose was further studied by analyzing chemical composition, powder X-ray diffraction for cellulose structure, NMR and SEC for lignin dissolution/depolymerization, and glycome profiling for cell wall modifications. 27486479 1 28 theme greenhouse 152:161 arg1 emissions 167:175 greenhouse gas emissions 152:175 greenhouse gas emissions 152:175 BACKGROUND Concerns around greenhouse gas emissions necessitate the development of sustainable processes for the production of chemicals, materials, and fuels from alternative renewable sources. 27486479 0 29 theme ionic 76:80 arg1 conditions 113:122 aqueous ionic liquid at low severity process conditions 68:122 aqueous ionic liquid at low severity process conditions 68:122 Activation of lignocellulosic biomass for higher sugar yields using aqueous ionic liquid at low severity process conditions. 27486479 5 30 theme mild 1113:1116 arg1 50 °C 1141:1145 50 °C 1141:1145 50 °C 1141:1145 RESULTS We have developed a highly effective pretreatment technology utilizing the relatively inexpensive IL comprised tetrabutylammonium [TBA](+) and hydroxide [OH](-) ions that generate high glucose yields (~95 %) after pretreatment at very mild processing conditions (50 °C). 27486479 5 30 theme mild 1113:1116 arg1 conditions 1129:1138 very mild processing conditions 1108:1138 very mild processing conditions (50 °C) 1108:1146 RESULTS We have developed a highly effective pretreatment technology utilizing the relatively inexpensive IL comprised tetrabutylammonium [TBA](+) and hydroxide [OH](-) ions that generate high glucose yields (~95 %) after pretreatment at very mild processing conditions (50 °C). 27486479 5 31 theme pretreatment 915:926 arg1 technology 928:937 a highly effective pretreatment technology 896:937 a highly effective pretreatment technology 896:937 RESULTS We have developed a highly effective pretreatment technology utilizing the relatively inexpensive IL comprised tetrabutylammonium [TBA](+) and hydroxide [OH](-) ions that generate high glucose yields (~95 %) after pretreatment at very mild processing conditions (50 °C). 27486479 9 32 dep [C2C1Im 2089:2095 arg1 [OAc 2097:2100 [OAc 2097:2100 [OAc 2097:2100 CONCLUSIONS By leveraging the benefits of ILs that are effective at very mild processing conditions, such as [TBA][OH], lignocellulosic biomass can be pretreated at similar efficiency as top performing conventional ILs, such as 1-ethyl-3-methylimidazolium acetate [C2C1Im][OAc], but at much lower temperatures, and with less than half the IL normally required to be effective. 27486479 11 33 theme biomass 2387:2393 arg1 pretreatment 2395:2406 biomass pretreatment 2387:2406 biomass pretreatment 2387:2406 This approach to biomass pretreatment at lower temperatures could be transformative in the affordability and energy efficiency of lignocellulosic biorefineries. 27486479 6 34 theme lignin 1329:1334 arg1 dissolution/depolymerization 1336:1363 lignin dissolution/depolymerization 1329:1363 lignin dissolution/depolymerization 1329:1363 The efficiency of [TBA][OH] pretreatment of lignocellulose was further studied by analyzing chemical composition, powder X-ray diffraction for cellulose structure, NMR and SEC for lignin dissolution/depolymerization, and glycome profiling for cell wall modifications. 27486479 7 35 theme [TBA 1568:1571 arg1 mobility 1556:1563 the ionic mobility 1546:1563 the ionic mobility of [TBA][OH] 1546:1576 Glycome profiling experiments and computational results indicate that removal of the noncellulosic polysaccharides occurs due to the ionic mobility of [TBA][OH] and is the key factor in determining pretreatment efficiency. 27486479 10 36 theme biomass 2323:2329 arg1 lignin 2284:2289 lignin 2284:2289 lignin 2284:2289 [TBA][OH] IL is more reactive in terms of ionic mobility which extends removal of lignin and noncellulosic components of biomass at the lower temperature pretreatment. 27486479 10 36 theme biomass 2323:2329 arg1 components 2309:2318 noncellulosic components 2295:2318 noncellulosic components of biomass 2295:2329 [TBA][OH] IL is more reactive in terms of ionic mobility which extends removal of lignin and noncellulosic components of biomass at the lower temperature pretreatment. 27486479 9 37 theme similar 1990:1996 arg1 efficiency 1998:2007 similar efficiency 1990:2007 similar efficiency as top performing conventional ILs, such as 1-ethyl-3-methylimidazolium acetate [C2C1Im][OAc] 1990:2101 CONCLUSIONS By leveraging the benefits of ILs that are effective at very mild processing conditions, such as [TBA][OH], lignocellulosic biomass can be pretreated at similar efficiency as top performing conventional ILs, such as 1-ethyl-3-methylimidazolium acetate [C2C1Im][OAc], but at much lower temperatures, and with less than half the IL normally required to be effective. 27486479 0 38 theme severity 96:103 arg1 process 105:111 low severity process 92:111 low severity process 92:111 Activation of lignocellulosic biomass for higher sugar yields using aqueous ionic liquid at low severity process conditions. 27486479 4 39 theme energy 750:755 arg1 processing 767:776 energy intensive processing 750:776 energy intensive processing conditions (>140 °C, 3 h) 750:802 Conventional ILs are relatively expensive in terms of purchase price, and the most effective imidazolium-based ILs also require energy intensive processing conditions (>140 °C, 3 h) to release >90 % fermentable sugar yields after saccharification. 27486479 3 40 theme Certain 440:446 arg1 liquids 454:460 Certain ionic liquids 440:460 Certain ionic liquids (ILs) 440:466 Certain ionic liquids (ILs) are very effective at disrupting the plant cell walls of lignocellulose, and generate a substrate that is effectively hydrolyzed into fermentable sugars. 27486479 3 40 theme Certain 440:446 arg1 ILs 463:465 ILs 463:465 ILs 463:465 Certain ionic liquids (ILs) are very effective at disrupting the plant cell walls of lignocellulose, and generate a substrate that is effectively hydrolyzed into fermentable sugars. 27486479 11 41 theme lignocellulosic 2500:2514 arg1 biorefineries 2516:2528 lignocellulosic biorefineries 2500:2528 lignocellulosic biorefineries 2500:2528 This approach to biomass pretreatment at lower temperatures could be transformative in the affordability and energy efficiency of lignocellulosic biorefineries. 27486479 0 42 theme lignocellulosic 14:28 arg1 biomass 30:36 lignocellulosic biomass 14:36 lignocellulosic biomass for higher sugar yields 14:60 Activation of lignocellulosic biomass for higher sugar yields using aqueous ionic liquid at low severity process conditions. 27486479 1 43 theme renewable 301:309 arg1 sources 311:317 alternative renewable sources 289:317 alternative renewable sources 289:317 BACKGROUND Concerns around greenhouse gas emissions necessitate the development of sustainable processes for the production of chemicals, materials, and fuels from alternative renewable sources. 27486479 7 44 theme ionic 1550:1554 arg1 mobility 1556:1563 the ionic mobility 1546:1563 the ionic mobility of [TBA][OH] 1546:1576 Glycome profiling experiments and computational results indicate that removal of the noncellulosic polysaccharides occurs due to the ionic mobility of [TBA][OH] and is the key factor in determining pretreatment efficiency. 27486479 5 45 theme tetrabutylammonium 989:1006 arg1 [TBA 1008:1011 tetrabutylammonium [TBA] 989:1012 tetrabutylammonium [TBA] 989:1012 RESULTS We have developed a highly effective pretreatment technology utilizing the relatively inexpensive IL comprised tetrabutylammonium [TBA](+) and hydroxide [OH](-) ions that generate high glucose yields (~95 %) after pretreatment at very mild processing conditions (50 °C). 27486479 4 46 theme % 819:819 arg1 yields 839:844 >90 % fermentable sugar yields 815:844 >90 % fermentable sugar yields 815:844 Conventional ILs are relatively expensive in terms of purchase price, and the most effective imidazolium-based ILs also require energy intensive processing conditions (>140 °C, 3 h) to release >90 % fermentable sugar yields after saccharification. 27486479 2 47 theme bioenergy 418:426 arg1 production 428:437 renewable bioenergy production 408:437 renewable bioenergy production 408:437 The lignocellulosic plant cell walls are one of the most abundant sources of carbon for renewable bioenergy production. 27486479 6 48 theme wall 1397:1400 arg1 modifications 1402:1414 cell wall modifications 1392:1414 cell wall modifications 1392:1414 The efficiency of [TBA][OH] pretreatment of lignocellulose was further studied by analyzing chemical composition, powder X-ray diffraction for cellulose structure, NMR and SEC for lignin dissolution/depolymerization, and glycome profiling for cell wall modifications. 27486479 5 49 dep RESULTS 870:876 arg1 developed 886:894 developed 886:894 have developed a highly effective pretreatment technology utilizing the relatively inexpensive IL comprised tetrabutylammonium [TBA](+) and hydroxide [OH](-) ions that generate high glucose yields (~95 %) after pretreatment at very mild processing conditions (50 °C) 881:1146 RESULTS We have developed a highly effective pretreatment technology utilizing the relatively inexpensive IL comprised tetrabutylammonium [TBA](+) and hydroxide [OH](-) ions that generate high glucose yields (~95 %) after pretreatment at very mild processing conditions (50 °C). 27486479 0 50 theme sugar 49:53 arg1 yields 55:60 higher sugar yields 42:60 higher sugar yields 42:60 Activation of lignocellulosic biomass for higher sugar yields using aqueous ionic liquid at low severity process conditions. 27486479 10 51 from reactive 2223:2230 arg1 terms 2235:2239 terms 2235:2239 terms of ionic mobility which extends removal of lignin and noncellulosic components of biomass at the lower temperature pretreatment 2235:2367 [TBA][OH] IL is more reactive in terms of ionic mobility which extends removal of lignin and noncellulosic components of biomass at the lower temperature pretreatment. 27486479 9 52 theme 1-ethyl-3-methylimidazolium 2053:2079 arg1 acetate 2081:2087 1-ethyl-3-methylimidazolium acetate 2053:2087 1-ethyl-3-methylimidazolium acetate [C2C1Im][OAc] 2053:2101 CONCLUSIONS By leveraging the benefits of ILs that are effective at very mild processing conditions, such as [TBA][OH], lignocellulosic biomass can be pretreated at similar efficiency as top performing conventional ILs, such as 1-ethyl-3-methylimidazolium acetate [C2C1Im][OAc], but at much lower temperatures, and with less than half the IL normally required to be effective. 27486479 8 53 theme modeling 1648:1655 arg1 analysis 1675:1682 Process modeling and energy demand analysis 1640:1682 Process modeling and energy demand analysis 1640:1682 Process modeling and energy demand analysis suggests that this [TBA][OH] pretreatment could potentially reduce the energy required in the pretreatment unit operation by more than 75 %. 27486479 7 54 theme noncellulosic 1502:1514 arg1 polysaccharides 1516:1530 the noncellulosic polysaccharides 1498:1530 the noncellulosic polysaccharides 1498:1530 Glycome profiling experiments and computational results indicate that removal of the noncellulosic polysaccharides occurs due to the ionic mobility of [TBA][OH] and is the key factor in determining pretreatment efficiency. 27486479 10 55 from terms 2235:2239 arg1 reactive 2223:2230 reactive 2223:2230 reactive 2223:2230 [TBA][OH] IL is more reactive in terms of ionic mobility which extends removal of lignin and noncellulosic components of biomass at the lower temperature pretreatment. 27486479 2 56 theme abundant 377:384 arg1 sources 386:392 the most abundant sources 368:392 the most abundant sources of carbon for renewable bioenergy production 368:437 The lignocellulosic plant cell walls are one of the most abundant sources of carbon for renewable bioenergy production. 27486479 8 57 theme energy 1661:1666 arg1 demand 1668:1673 energy demand 1661:1673 energy demand 1661:1673 Process modeling and energy demand analysis suggests that this [TBA][OH] pretreatment could potentially reduce the energy required in the pretreatment unit operation by more than 75 %. 27486479 1 58 theme chemicals 252:260 arg1 production 238:247 the production 234:247 the production of chemicals, materials, and fuels from alternative renewable sources 234:317 BACKGROUND Concerns around greenhouse gas emissions necessitate the development of sustainable processes for the production of chemicals, materials, and fuels from alternative renewable sources. 27486479 5 59 theme [OH 1031:1033 arg1 ions 1039:1042 hydroxide [OH](-) ions 1021:1042 hydroxide [OH](-) ions that generate high glucose yields (~95 %) after pretreatment at very mild processing conditions (50 °C) 1021:1146 RESULTS We have developed a highly effective pretreatment technology utilizing the relatively inexpensive IL comprised tetrabutylammonium [TBA](+) and hydroxide [OH](-) ions that generate high glucose yields (~95 %) after pretreatment at very mild processing conditions (50 °C). 27486479 9 60 theme ILs 1867:1869 arg1 benefits 1855:1862 the benefits 1851:1862 the benefits of ILs that are effective at very mild processing conditions, such as [TBA][OH] 1851:1942 CONCLUSIONS By leveraging the benefits of ILs that are effective at very mild processing conditions, such as [TBA][OH], lignocellulosic biomass can be pretreated at similar efficiency as top performing conventional ILs, such as 1-ethyl-3-methylimidazolium acetate [C2C1Im][OAc], but at much lower temperatures, and with less than half the IL normally required to be effective. 27486479 4 61 theme Conventional 622:633 arg1 ILs 635:637 Conventional ILs 622:637 Conventional ILs 622:637 Conventional ILs are relatively expensive in terms of purchase price, and the most effective imidazolium-based ILs also require energy intensive processing conditions (>140 °C, 3 h) to release >90 % fermentable sugar yields after saccharification. 27486479 6 62 theme powder 1263:1268 arg1 diffraction 1276:1286 powder X-ray diffraction 1263:1286 powder X-ray diffraction for cellulose structure 1263:1310 The efficiency of [TBA][OH] pretreatment of lignocellulose was further studied by analyzing chemical composition, powder X-ray diffraction for cellulose structure, NMR and SEC for lignin dissolution/depolymerization, and glycome profiling for cell wall modifications. 27486479 3 63 theme plant 505:509 arg1 walls 516:520 the plant cell walls 501:520 the plant cell walls of lignocellulose 501:538 Certain ionic liquids (ILs) are very effective at disrupting the plant cell walls of lignocellulose, and generate a substrate that is effectively hydrolyzed into fermentable sugars. 27486479 1 64 theme materials 263:271 arg1 production 238:247 the production 234:247 the production of chemicals, materials, and fuels from alternative renewable sources 234:317 BACKGROUND Concerns around greenhouse gas emissions necessitate the development of sustainable processes for the production of chemicals, materials, and fuels from alternative renewable sources. 27486479 5 65 from conditions 1129:1138 arg1 pretreatment 1092:1103 pretreatment 1092:1103 pretreatment at very mild processing conditions (50 °C) 1092:1146 RESULTS We have developed a highly effective pretreatment technology utilizing the relatively inexpensive IL comprised tetrabutylammonium [TBA](+) and hydroxide [OH](-) ions that generate high glucose yields (~95 %) after pretreatment at very mild processing conditions (50 °C). 27486479 4 66 theme sugar 833:837 arg1 yields 839:844 >90 % fermentable sugar yields 815:844 >90 % fermentable sugar yields 815:844 Conventional ILs are relatively expensive in terms of purchase price, and the most effective imidazolium-based ILs also require energy intensive processing conditions (>140 °C, 3 h) to release >90 % fermentable sugar yields after saccharification. 27486479 11 67 from affordability 2461:2473 arg1 transformative 2439:2452 transformative 2439:2452 transformative 2439:2452 This approach to biomass pretreatment at lower temperatures could be transformative in the affordability and energy efficiency of lignocellulosic biorefineries. 27486479 9 68 dep half 2155:2158 arg1 IL 2164:2165 the IL 2160:2165 half the IL normally required to be effective 2155:2199 CONCLUSIONS By leveraging the benefits of ILs that are effective at very mild processing conditions, such as [TBA][OH], lignocellulosic biomass can be pretreated at similar efficiency as top performing conventional ILs, such as 1-ethyl-3-methylimidazolium acetate [C2C1Im][OAc], but at much lower temperatures, and with less than half the IL normally required to be effective. 27486479 5 69 theme effective 905:913 arg1 technology 928:937 a highly effective pretreatment technology 896:937 a highly effective pretreatment technology 896:937 RESULTS We have developed a highly effective pretreatment technology utilizing the relatively inexpensive IL comprised tetrabutylammonium [TBA](+) and hydroxide [OH](-) ions that generate high glucose yields (~95 %) after pretreatment at very mild processing conditions (50 °C). 27486479 8 70 theme [OH 1708:1710 arg1 pretreatment 1713:1724 this [TBA][OH] pretreatment 1698:1724 this [TBA][OH] pretreatment 1698:1724 Process modeling and energy demand analysis suggests that this [TBA][OH] pretreatment could potentially reduce the energy required in the pretreatment unit operation by more than 75 %. 27486479 9 71 dep CONCLUSIONS 1825:1835 arg1 pretreated 1976:1985 pretreated 1976:1985 can be pretreated at similar efficiency as top performing conventional ILs, such as 1-ethyl-3-methylimidazolium acetate [C2C1Im][OAc], but at much lower temperatures, and with less than half the IL normally required to be effective 1969:2199 CONCLUSIONS By leveraging the benefits of ILs that are effective at very mild processing conditions, such as [TBA][OH], lignocellulosic biomass can be pretreated at similar efficiency as top performing conventional ILs, such as 1-ethyl-3-methylimidazolium acetate [C2C1Im][OAc], but at much lower temperatures, and with less than half the IL normally required to be effective. 27486479 3 72 theme lignocellulose 525:538 arg1 walls 516:520 the plant cell walls 501:520 the plant cell walls of lignocellulose 501:538 Certain ionic liquids (ILs) are very effective at disrupting the plant cell walls of lignocellulose, and generate a substrate that is effectively hydrolyzed into fermentable sugars. 27486479 8 73 theme [TBA 1703:1706 arg1 pretreatment 1713:1724 this [TBA][OH] pretreatment 1698:1724 this [TBA][OH] pretreatment 1698:1724 Process modeling and energy demand analysis suggests that this [TBA][OH] pretreatment could potentially reduce the energy required in the pretreatment unit operation by more than 75 %. 27486479 7 74 theme Glycome 1417:1423 arg1 experiments 1435:1445 Glycome profiling experiments 1417:1445 Glycome profiling experiments 1417:1445 Glycome profiling experiments and computational results indicate that removal of the noncellulosic polysaccharides occurs due to the ionic mobility of [TBA][OH] and is the key factor in determining pretreatment efficiency. 27486479 9 75 theme mild 1898:1901 arg1 conditions 1914:1923 very mild processing conditions 1893:1923 very mild processing conditions 1893:1923 CONCLUSIONS By leveraging the benefits of ILs that are effective at very mild processing conditions, such as [TBA][OH], lignocellulosic biomass can be pretreated at similar efficiency as top performing conventional ILs, such as 1-ethyl-3-methylimidazolium acetate [C2C1Im][OAc], but at much lower temperatures, and with less than half the IL normally required to be effective. 27486479 9 76 theme lower 2116:2120 arg1 temperatures 2122:2133 much lower temperatures 2111:2133 much lower temperatures 2111:2133 CONCLUSIONS By leveraging the benefits of ILs that are effective at very mild processing conditions, such as [TBA][OH], lignocellulosic biomass can be pretreated at similar efficiency as top performing conventional ILs, such as 1-ethyl-3-methylimidazolium acetate [C2C1Im][OAc], but at much lower temperatures, and with less than half the IL normally required to be effective. 27486479 2 77 theme plant 340:344 arg1 sources 386:392 the most abundant sources 368:392 the most abundant sources of carbon for renewable bioenergy production 368:437 The lignocellulosic plant cell walls are one of the most abundant sources of carbon for renewable bioenergy production. 27486479 2 77 theme plant 340:344 arg1 one 361:363 one 361:363 one 361:363 The lignocellulosic plant cell walls are one of the most abundant sources of carbon for renewable bioenergy production. 27486479 2 77 theme plant 340:344 arg1 walls 351:355 The lignocellulosic plant cell walls 320:355 The lignocellulosic plant cell walls 320:355 The lignocellulosic plant cell walls are one of the most abundant sources of carbon for renewable bioenergy production. 27486479 4 78 from terms 667:671 arg1 expensive 654:662 expensive 654:662 expensive 654:662 Conventional ILs are relatively expensive in terms of purchase price, and the most effective imidazolium-based ILs also require energy intensive processing conditions (>140 °C, 3 h) to release >90 % fermentable sugar yields after saccharification. 27486479 4 79 theme purchase 676:683 arg1 price 685:689 purchase price 676:689 purchase price 676:689 Conventional ILs are relatively expensive in terms of purchase price, and the most effective imidazolium-based ILs also require energy intensive processing conditions (>140 °C, 3 h) to release >90 % fermentable sugar yields after saccharification. 27486479 4 80 from expensive 654:662 arg1 terms 667:671 terms 667:671 terms of purchase price 667:689 Conventional ILs are relatively expensive in terms of purchase price, and the most effective imidazolium-based ILs also require energy intensive processing conditions (>140 °C, 3 h) to release >90 % fermentable sugar yields after saccharification. 27486479 1 81 theme sustainable 208:218 arg1 processes 220:228 sustainable processes 208:228 sustainable processes for the production of chemicals, materials, and fuels from alternative renewable sources 208:317 BACKGROUND Concerns around greenhouse gas emissions necessitate the development of sustainable processes for the production of chemicals, materials, and fuels from alternative renewable sources. 27486479 7 82 theme pretreatment 1615:1626 arg1 efficiency 1628:1637 pretreatment efficiency 1615:1637 pretreatment efficiency 1615:1637 Glycome profiling experiments and computational results indicate that removal of the noncellulosic polysaccharides occurs due to the ionic mobility of [TBA][OH] and is the key factor in determining pretreatment efficiency. 27486479 10 83 theme ionic 2244:2248 arg1 mobility 2250:2257 ionic mobility 2244:2257 ionic mobility which extends removal of lignin and noncellulosic components of biomass at the lower temperature pretreatment 2244:2367 [TBA][OH] IL is more reactive in terms of ionic mobility which extends removal of lignin and noncellulosic components of biomass at the lower temperature pretreatment. 27486479 4 84 dep conditions 778:787 arg1 3 h 799:801 3 h 799:801 3 h 799:801 Conventional ILs are relatively expensive in terms of purchase price, and the most effective imidazolium-based ILs also require energy intensive processing conditions (>140 °C, 3 h) to release >90 % fermentable sugar yields after saccharification. 27486479 4 84 dep conditions 778:787 arg1 >140 °C 790:796 >140 °C 790:796 >140 °C 790:796 Conventional ILs are relatively expensive in terms of purchase price, and the most effective imidazolium-based ILs also require energy intensive processing conditions (>140 °C, 3 h) to release >90 % fermentable sugar yields after saccharification. 27486479 6 85 theme lignocellulose 1193:1206 arg1 pretreatment 1177:1188 [TBA][OH] pretreatment 1167:1188 [TBA][OH] pretreatment of lignocellulose 1167:1206 The efficiency of [TBA][OH] pretreatment of lignocellulose was further studied by analyzing chemical composition, powder X-ray diffraction for cellulose structure, NMR and SEC for lignin dissolution/depolymerization, and glycome profiling for cell wall modifications. 27486479 6 86 theme cellulose 1292:1300 arg1 structure 1302:1310 cellulose structure 1292:1310 cellulose structure 1292:1310 The efficiency of [TBA][OH] pretreatment of lignocellulose was further studied by analyzing chemical composition, powder X-ray diffraction for cellulose structure, NMR and SEC for lignin dissolution/depolymerization, and glycome profiling for cell wall modifications. 27486479 4 87 dep processing 767:776 arg1 conditions 778:787 conditions 778:787 energy intensive processing conditions (>140 °C, 3 h) 750:802 Conventional ILs are relatively expensive in terms of purchase price, and the most effective imidazolium-based ILs also require energy intensive processing conditions (>140 °C, 3 h) to release >90 % fermentable sugar yields after saccharification. 27486479 11 88 from temperatures 2417:2428 arg1 approach 2375:2382 This approach 2370:2382 This approach to biomass pretreatment at lower temperatures 2370:2428 This approach to biomass pretreatment at lower temperatures could be transformative in the affordability and energy efficiency of lignocellulosic biorefineries. 27486479 7 89 theme key 1589:1591 arg1 factor 1593:1598 the key factor 1585:1598 the key factor 1585:1598 Glycome profiling experiments and computational results indicate that removal of the noncellulosic polysaccharides occurs due to the ionic mobility of [TBA][OH] and is the key factor in determining pretreatment efficiency. 27486479 0 90 from process 105:111 arg1 liquid 82:87 liquid 82:87 liquid 82:87 Activation of lignocellulosic biomass for higher sugar yields using aqueous ionic liquid at low severity process conditions. 27486479 6 91 theme pretreatment 1177:1188 arg1 efficiency 1153:1162 The efficiency 1149:1162 The efficiency of [TBA][OH] pretreatment of lignocellulose 1149:1206 The efficiency of [TBA][OH] pretreatment of lignocellulose was further studied by analyzing chemical composition, powder X-ray diffraction for cellulose structure, NMR and SEC for lignin dissolution/depolymerization, and glycome profiling for cell wall modifications. 27486479 4 92 theme effective 705:713 arg1 ILs 733:735 the most effective imidazolium-based ILs 696:735 the most effective imidazolium-based ILs 696:735 Conventional ILs are relatively expensive in terms of purchase price, and the most effective imidazolium-based ILs also require energy intensive processing conditions (>140 °C, 3 h) to release >90 % fermentable sugar yields after saccharification. 27486479 6 93 theme [OH 1172:1174 arg1 pretreatment 1177:1188 [TBA][OH] pretreatment 1167:1188 [TBA][OH] pretreatment of lignocellulose 1167:1206 The efficiency of [TBA][OH] pretreatment of lignocellulose was further studied by analyzing chemical composition, powder X-ray diffraction for cellulose structure, NMR and SEC for lignin dissolution/depolymerization, and glycome profiling for cell wall modifications. 27486479 6 94 dep [OH 1172:1174 arg1 [TBA 1167:1170 [TBA 1167:1170 [TBA 1167:1170 The efficiency of [TBA][OH] pretreatment of lignocellulose was further studied by analyzing chemical composition, powder X-ray diffraction for cellulose structure, NMR and SEC for lignin dissolution/depolymerization, and glycome profiling for cell wall modifications. 27486479 0 95 theme aqueous 68:74 arg1 conditions 113:122 aqueous ionic liquid at low severity process conditions 68:122 aqueous ionic liquid at low severity process conditions 68:122 Activation of lignocellulosic biomass for higher sugar yields using aqueous ionic liquid at low severity process conditions. 27486479 5 96 theme high 1058:1061 arg1 yields 1071:1076 high glucose yields 1058:1076 high glucose yields (~95 %) 1058:1084 RESULTS We have developed a highly effective pretreatment technology utilizing the relatively inexpensive IL comprised tetrabutylammonium [TBA](+) and hydroxide [OH](-) ions that generate high glucose yields (~95 %) after pretreatment at very mild processing conditions (50 °C). 27486479 5 96 theme high 1058:1061 arg1 % 1083:1083 ~95 % 1079:1083 ~95 % 1079:1083 RESULTS We have developed a highly effective pretreatment technology utilizing the relatively inexpensive IL comprised tetrabutylammonium [TBA](+) and hydroxide [OH](-) ions that generate high glucose yields (~95 %) after pretreatment at very mild processing conditions (50 °C). 27486479 10 97 theme noncellulosic 2295:2307 arg1 components 2309:2318 noncellulosic components 2295:2318 noncellulosic components of biomass 2295:2329 [TBA][OH] IL is more reactive in terms of ionic mobility which extends removal of lignin and noncellulosic components of biomass at the lower temperature pretreatment. 27486479 11 98 theme lower 2411:2415 arg1 temperatures 2417:2428 lower temperatures 2411:2428 lower temperatures 2411:2428 This approach to biomass pretreatment at lower temperatures could be transformative in the affordability and energy efficiency of lignocellulosic biorefineries. 27486479 0 99 theme liquid 82:87 arg1 conditions 113:122 aqueous ionic liquid at low severity process conditions 68:122 aqueous ionic liquid at low severity process conditions 68:122 Activation of lignocellulosic biomass for higher sugar yields using aqueous ionic liquid at low severity process conditions. 27486479 8 100 theme unit 1791:1794 arg1 operation 1796:1804 the pretreatment unit operation 1774:1804 the pretreatment unit operation 1774:1804 Process modeling and energy demand analysis suggests that this [TBA][OH] pretreatment could potentially reduce the energy required in the pretreatment unit operation by more than 75 %. 27486479 1 101 theme gas 163:165 arg1 emissions 167:175 greenhouse gas emissions 152:175 greenhouse gas emissions 152:175 BACKGROUND Concerns around greenhouse gas emissions necessitate the development of sustainable processes for the production of chemicals, materials, and fuels from alternative renewable sources. 27486479 9 102 dep acetate 2081:2087 arg1 [C2C1Im 2089:2095 [C2C1Im 2089:2095 [C2C1Im 2089:2095 CONCLUSIONS By leveraging the benefits of ILs that are effective at very mild processing conditions, such as [TBA][OH], lignocellulosic biomass can be pretreated at similar efficiency as top performing conventional ILs, such as 1-ethyl-3-methylimidazolium acetate [C2C1Im][OAc], but at much lower temperatures, and with less than half the IL normally required to be effective. 27486479 10 103 theme lignin 2284:2289 arg1 removal 2273:2279 removal 2273:2279 removal of lignin and noncellulosic components of biomass 2273:2329 [TBA][OH] IL is more reactive in terms of ionic mobility which extends removal of lignin and noncellulosic components of biomass at the lower temperature pretreatment. 27486479 0 104 theme low 92:94 arg1 process 105:111 low severity process 92:111 low severity process 92:111 Activation of lignocellulosic biomass for higher sugar yields using aqueous ionic liquid at low severity process conditions. 27486479 5 105 theme processing 1118:1127 arg1 50 °C 1141:1145 50 °C 1141:1145 50 °C 1141:1145 RESULTS We have developed a highly effective pretreatment technology utilizing the relatively inexpensive IL comprised tetrabutylammonium [TBA](+) and hydroxide [OH](-) ions that generate high glucose yields (~95 %) after pretreatment at very mild processing conditions (50 °C). 27486479 5 105 theme processing 1118:1127 arg1 conditions 1129:1138 very mild processing conditions 1108:1138 very mild processing conditions (50 °C) 1108:1146 RESULTS We have developed a highly effective pretreatment technology utilizing the relatively inexpensive IL comprised tetrabutylammonium [TBA](+) and hydroxide [OH](-) ions that generate high glucose yields (~95 %) after pretreatment at very mild processing conditions (50 °C). 27486479 10 106 dep temperature 2344:2354 arg1 pretreatment 2356:2367 pretreatment 2356:2367 the lower temperature pretreatment 2334:2367 [TBA][OH] IL is more reactive in terms of ionic mobility which extends removal of lignin and noncellulosic components of biomass at the lower temperature pretreatment. 27486479 2 107 theme carbon 397:402 arg1 sources 386:392 the most abundant sources 368:392 the most abundant sources of carbon for renewable bioenergy production 368:437 The lignocellulosic plant cell walls are one of the most abundant sources of carbon for renewable bioenergy production. 27486479 5 108 theme inexpensive 964:974 arg1 IL 976:977 the relatively inexpensive IL 949:977 the relatively inexpensive IL comprised tetrabutylammonium [TBA](+) and hydroxide [OH](-) ions that generate high glucose yields (~95 %) after pretreatment at very mild processing conditions (50 °C) 949:1146 RESULTS We have developed a highly effective pretreatment technology utilizing the relatively inexpensive IL comprised tetrabutylammonium [TBA](+) and hydroxide [OH](-) ions that generate high glucose yields (~95 %) after pretreatment at very mild processing conditions (50 °C). 27486479 2 109 theme sources 386:392 arg1 sources 386:392 the most abundant sources 368:392 the most abundant sources of carbon for renewable bioenergy production 368:437 The lignocellulosic plant cell walls are one of the most abundant sources of carbon for renewable bioenergy production. 27486479 2 109 theme sources 386:392 arg1 one 361:363 one 361:363 one 361:363 The lignocellulosic plant cell walls are one of the most abundant sources of carbon for renewable bioenergy production. 27486479 2 109 theme sources 386:392 arg1 walls 351:355 The lignocellulosic plant cell walls 320:355 The lignocellulosic plant cell walls 320:355 The lignocellulosic plant cell walls are one of the most abundant sources of carbon for renewable bioenergy production. 27486479 0 110 theme biomass 30:36 arg1 Activation 0:9 Activation 0:9 Activation of lignocellulosic biomass for higher sugar yields 0:60 Activation of lignocellulosic biomass for higher sugar yields using aqueous ionic liquid at low severity process conditions. 27486479 1 111 theme alternative 289:299 arg1 sources 311:317 alternative renewable sources 289:317 alternative renewable sources 289:317 BACKGROUND Concerns around greenhouse gas emissions necessitate the development of sustainable processes for the production of chemicals, materials, and fuels from alternative renewable sources. 27486479 10 112 theme lower 2338:2342 arg1 temperature 2344:2354 the lower temperature pretreatment 2334:2367 the lower temperature pretreatment 2334:2367 [TBA][OH] IL is more reactive in terms of ionic mobility which extends removal of lignin and noncellulosic components of biomass at the lower temperature pretreatment. 27486479 9 113 theme conventional 2027:2038 arg1 acetate 2081:2087 1-ethyl-3-methylimidazolium acetate 2053:2087 1-ethyl-3-methylimidazolium acetate [C2C1Im][OAc] 2053:2101 CONCLUSIONS By leveraging the benefits of ILs that are effective at very mild processing conditions, such as [TBA][OH], lignocellulosic biomass can be pretreated at similar efficiency as top performing conventional ILs, such as 1-ethyl-3-methylimidazolium acetate [C2C1Im][OAc], but at much lower temperatures, and with less than half the IL normally required to be effective. 27486479 9 113 theme conventional 2027:2038 arg1 ILs 2040:2042 conventional ILs 2027:2042 conventional ILs 2027:2042 CONCLUSIONS By leveraging the benefits of ILs that are effective at very mild processing conditions, such as [TBA][OH], lignocellulosic biomass can be pretreated at similar efficiency as top performing conventional ILs, such as 1-ethyl-3-methylimidazolium acetate [C2C1Im][OAc], but at much lower temperatures, and with less than half the IL normally required to be effective. 27486479 4 114 theme intensive 757:765 arg1 processing 767:776 energy intensive processing 750:776 energy intensive processing conditions (>140 °C, 3 h) 750:802 Conventional ILs are relatively expensive in terms of purchase price, and the most effective imidazolium-based ILs also require energy intensive processing conditions (>140 °C, 3 h) to release >90 % fermentable sugar yields after saccharification. 27486479 0 115 theme higher 42:47 arg1 yields 55:60 higher sugar yields 42:60 higher sugar yields 42:60 Activation of lignocellulosic biomass for higher sugar yields using aqueous ionic liquid at low severity process conditions. 27486479 4 116 theme >90  815:818 arg1 yields 839:844 >90 % fermentable sugar yields 815:844 >90 % fermentable sugar yields 815:844 Conventional ILs are relatively expensive in terms of purchase price, and the most effective imidazolium-based ILs also require energy intensive processing conditions (>140 °C, 3 h) to release >90 % fermentable sugar yields after saccharification. 27486479 2 117 theme renewable 408:416 arg1 production 428:437 renewable bioenergy production 408:437 renewable bioenergy production 408:437 The lignocellulosic plant cell walls are one of the most abundant sources of carbon for renewable bioenergy production. 27486479 6 118 theme cell 1392:1395 arg1 modifications 1402:1414 cell wall modifications 1392:1414 cell wall modifications 1392:1414 The efficiency of [TBA][OH] pretreatment of lignocellulose was further studied by analyzing chemical composition, powder X-ray diffraction for cellulose structure, NMR and SEC for lignin dissolution/depolymerization, and glycome profiling for cell wall modifications. 27486479 4 119 theme fermentable 821:831 arg1 yields 839:844 >90 % fermentable sugar yields 815:844 >90 % fermentable sugar yields 815:844 Conventional ILs are relatively expensive in terms of purchase price, and the most effective imidazolium-based ILs also require energy intensive processing conditions (>140 °C, 3 h) to release >90 % fermentable sugar yields after saccharification. 27486479 2 120 theme cell 346:349 arg1 sources 386:392 the most abundant sources 368:392 the most abundant sources of carbon for renewable bioenergy production 368:437 The lignocellulosic plant cell walls are one of the most abundant sources of carbon for renewable bioenergy production. 27486479 2 120 theme cell 346:349 arg1 one 361:363 one 361:363 one 361:363 The lignocellulosic plant cell walls are one of the most abundant sources of carbon for renewable bioenergy production. 27486479 2 120 theme cell 346:349 arg1 walls 351:355 The lignocellulosic plant cell walls 320:355 The lignocellulosic plant cell walls 320:355 The lignocellulosic plant cell walls are one of the most abundant sources of carbon for renewable bioenergy production. 27486479 8 121 theme demand 1668:1673 arg1 analysis 1675:1682 Process modeling and energy demand analysis 1640:1682 Process modeling and energy demand analysis 1640:1682 Process modeling and energy demand analysis suggests that this [TBA][OH] pretreatment could potentially reduce the energy required in the pretreatment unit operation by more than 75 %. 27486479 11 122 from efficiency 2486:2495 arg1 transformative 2439:2452 transformative 2439:2452 transformative 2439:2452 This approach to biomass pretreatment at lower temperatures could be transformative in the affordability and energy efficiency of lignocellulosic biorefineries. 27486479 7 123 theme polysaccharides 1516:1530 arg1 removal 1487:1493 removal 1487:1493 removal of the noncellulosic polysaccharides 1487:1530 Glycome profiling experiments and computational results indicate that removal of the noncellulosic polysaccharides occurs due to the ionic mobility of [TBA][OH] and is the key factor in determining pretreatment efficiency. 27486479 5 124 theme hydroxide 1021:1029 arg1 [OH 1031:1033 hydroxide [OH] 1021:1034 hydroxide [OH] 1021:1034 RESULTS We have developed a highly effective pretreatment technology utilizing the relatively inexpensive IL comprised tetrabutylammonium [TBA](+) and hydroxide [OH](-) ions that generate high glucose yields (~95 %) after pretreatment at very mild processing conditions (50 °C). 26894828 14 0 theme species 1939:1945 arg1 dynamics 1917:1924 not only quantitative dynamics 1895:1924 not only quantitative dynamics of bacterial species 1895:1945 The model demonstrates not only quantitative dynamics of bacterial species, but also gives an ability to observe the emergent spatial structure and its alteration, depending on various feedback mechanisms. 26894828 14 1 dep dynamics 1917:1924 arg1 only 1899:1902 only 1899:1902 only 1899:1902 The model demonstrates not only quantitative dynamics of bacterial species, but also gives an ability to observe the emergent spatial structure and its alteration, depending on various feedback mechanisms. 26894828 12 2 theme sensitive 1732:1740 arg1 strains 1742:1748 sensitive strains 1732:1748 sensitive strains 1732:1748 High fraction of bacterial community was shown to mutate during antibiotic treatment, though sensitive strains could become dominating after recovery. 26894828 5 3 from FINDINGS 650:657 arg1 work 667:670 this work 662:670 this work 662:670 METHODOLOGY/PRINCIPAL FINDINGS In this work we report an agent-based model of interactions between two bacterial species and between species and the gut. 26894828 3 4 theme community 328:336 arg1 influence 338:346 the community influence 324:346 the community influence on host health 324:361 Examination of the intestinal microbiome interactions is required for understanding of the community influence on host health. 26894828 4 5 theme microbiota 545:554 arg1 correction 556:565 microbiota correction 545:565 microbiota correction 545:565 Studies of the microbiome can provide insight on methods of improving health, including specific clinical procedures for individual microbial community composition modification and microbiota correction by colonizing with new bacterial species or dietary changes. 26894828 7 6 theme system 1029:1034 arg1 stability 1012:1020 stability 1012:1020 stability of the system 1012:1034 Antibiotic treatment was chosen as disturbance factor and used to investigate stability of the system. 26894828 6 7 theme acetate 913:919 arg1 fermentation 835:846 bacterial fermentation 825:846 bacterial fermentation of polysaccharides to acetate and propionate 825:891 The model is based on reactions describing bacterial fermentation of polysaccharides to acetate and propionate and fermentation of acetate to butyrate. 26894828 6 7 theme acetate 913:919 arg1 fermentation 897:908 fermentation 897:908 fermentation of acetate to butyrate 897:931 The model is based on reactions describing bacterial fermentation of polysaccharides to acetate and propionate and fermentation of acetate to butyrate. 26894828 7 8 theme Antibiotic 934:943 arg1 factor 981:986 disturbance factor 969:986 disturbance factor 969:986 Antibiotic treatment was chosen as disturbance factor and used to investigate stability of the system. 26894828 7 8 theme Antibiotic 934:943 arg1 treatment 945:953 Antibiotic treatment 934:953 Antibiotic treatment 934:953 Antibiotic treatment was chosen as disturbance factor and used to investigate stability of the system. 26894828 4 9 theme dietary 611:617 arg1 changes 619:625 dietary changes 611:625 dietary changes 611:625 Studies of the microbiome can provide insight on methods of improving health, including specific clinical procedures for individual microbial community composition modification and microbiota correction by colonizing with new bacterial species or dietary changes. 26894828 5 10 theme interactions 706:717 arg1 model 697:701 an agent-based model 682:701 an agent-based model of interactions between two bacterial species and between species and the gut 682:779 METHODOLOGY/PRINCIPAL FINDINGS In this work we report an agent-based model of interactions between two bacterial species and between species and the gut. 26894828 8 11 theme System 1037:1042 arg1 dependence 1096:1105 dependence 1096:1105 dependence on quantity of feedback interactions inside the community, therapy duration and amount of antibiotics 1096:1207 System recovery after antibiotic treatment was analyzed as dependence on quantity of feedback interactions inside the community, therapy duration and amount of antibiotics. 26894828 8 11 theme System 1037:1042 arg1 recovery 1044:1051 System recovery 1037:1051 System recovery after antibiotic treatment 1037:1078 System recovery after antibiotic treatment was analyzed as dependence on quantity of feedback interactions inside the community, therapy duration and amount of antibiotics. 26894828 12 12 theme bacterial 1656:1664 arg1 community 1666:1674 bacterial community 1656:1674 bacterial community 1656:1674 High fraction of bacterial community was shown to mutate during antibiotic treatment, though sensitive strains could become dominating after recovery. 26894828 4 13 theme individual 485:494 arg1 composition 516:526 individual microbial community composition modification and microbiota correction 485:565 composition 516:526 Studies of the microbiome can provide insight on methods of improving health, including specific clinical procedures for individual microbial community composition modification and microbiota correction by colonizing with new bacterial species or dietary changes. 26894828 8 14 theme antibiotic 1059:1068 arg1 treatment 1070:1078 antibiotic treatment 1059:1078 antibiotic treatment 1059:1078 System recovery after antibiotic treatment was analyzed as dependence on quantity of feedback interactions inside the community, therapy duration and amount of antibiotics. 26894828 11 15 dep CONCLUSION/SIGNIFICANCE 1474:1496 arg1 confirms 1508:1515 confirms 1508:1515 confirms a hypothesis of feedbacks 1508:1541 CONCLUSION/SIGNIFICANCE The model confirms a hypothesis of feedbacks mechanisms necessity for providing functionality and stability of the system after disturbance. 26894828 11 16 theme feedbacks 1533:1541 arg1 hypothesis 1519:1528 a hypothesis 1517:1528 a hypothesis of feedbacks 1517:1541 CONCLUSION/SIGNIFICANCE The model confirms a hypothesis of feedbacks mechanisms necessity for providing functionality and stability of the system after disturbance. 26894828 3 17 theme host 351:354 arg1 health 356:361 host health 351:361 host health 351:361 Examination of the intestinal microbiome interactions is required for understanding of the community influence on host health. 26894828 5 18 theme METHODOLOGY/PRINCIPAL 628:648 arg1 FINDINGS 650:657 METHODOLOGY/PRINCIPAL FINDINGS 628:657 METHODOLOGY/PRINCIPAL FINDINGS In this work we 628:673 METHODOLOGY/PRINCIPAL FINDINGS In this work we report an agent-based model of interactions between two bacterial species and between species and the gut. 26894828 8 19 theme interactions 1131:1142 arg1 quantity 1110:1117 quantity 1110:1117 quantity of feedback interactions inside the community, therapy duration and amount of antibiotics 1110:1207 System recovery after antibiotic treatment was analyzed as dependence on quantity of feedback interactions inside the community, therapy duration and amount of antibiotics. 26894828 6 20 theme polysaccharides 851:865 arg1 fermentation 835:846 bacterial fermentation 825:846 bacterial fermentation of polysaccharides to acetate and propionate 825:891 The model is based on reactions describing bacterial fermentation of polysaccharides to acetate and propionate and fermentation of acetate to butyrate. 26894828 6 20 theme polysaccharides 851:865 arg1 fermentation 897:908 fermentation 897:908 fermentation of acetate to butyrate 897:931 The model is based on reactions describing bacterial fermentation of polysaccharides to acetate and propionate and fermentation of acetate to butyrate. 26894828 4 21 from insight 402:408 arg1 methods 413:419 methods 413:419 methods of improving health 413:439 Studies of the microbiome can provide insight on methods of improving health, including specific clinical procedures for individual microbial community composition modification and microbiota correction by colonizing with new bacterial species or dietary changes. 26894828 4 22 theme community 506:514 arg1 composition 516:526 individual microbial community composition modification and microbiota correction 485:565 composition 516:526 Studies of the microbiome can provide insight on methods of improving health, including specific clinical procedures for individual microbial community composition modification and microbiota correction by colonizing with new bacterial species or dietary changes. 26894828 8 23 theme feedback 1122:1129 arg1 interactions 1131:1142 feedback interactions 1122:1142 feedback interactions inside the community, therapy duration and amount of antibiotics 1122:1207 System recovery after antibiotic treatment was analyzed as dependence on quantity of feedback interactions inside the community, therapy duration and amount of antibiotics. 26894828 1 24 theme BACKGROUND 77:86 arg1 microbiota 99:108 BACKGROUND Intestinal microbiota 77:108 BACKGROUND Intestinal microbiota 77:108 BACKGROUND Intestinal microbiota plays an important role in the human health. 26894828 0 25 theme Based 6:10 arg1 Modeling 12:19 Agent Based Modeling 0:19 Agent Based Modeling of Human Gut 0:32 Agent Based Modeling of Human Gut Microbiome Interactions and Perturbations. 26894828 4 26 theme microbial 496:504 arg1 composition 516:526 individual microbial community composition modification and microbiota correction 485:565 composition 516:526 Studies of the microbiome can provide insight on methods of improving health, including specific clinical procedures for individual microbial community composition modification and microbiota correction by colonizing with new bacterial species or dietary changes. 26894828 13 27 theme strains 1816:1822 arg1 recovery 1794:1801 The recovery 1790:1801 The recovery of sensitive strains 1790:1822 The recovery of sensitive strains is explained by fitness cost of the resistance. 26894828 11 28 theme system 1613:1618 arg1 stability 1596:1604 stability 1596:1604 stability 1596:1604 CONCLUSION/SIGNIFICANCE The model confirms a hypothesis of feedbacks mechanisms necessity for providing functionality and stability of the system after disturbance. 26894828 11 28 theme system 1613:1618 arg1 functionality 1578:1590 functionality 1578:1590 functionality 1578:1590 CONCLUSION/SIGNIFICANCE The model confirms a hypothesis of feedbacks mechanisms necessity for providing functionality and stability of the system after disturbance. 26894828 1 29 theme Intestinal 88:97 arg1 microbiota 99:108 BACKGROUND Intestinal microbiota 77:108 BACKGROUND Intestinal microbiota 77:108 BACKGROUND Intestinal microbiota plays an important role in the human health. 26894828 15 30 theme spatial 2117:2123 arg1 factor 2144:2149 a key factor 2138:2149 a key factor 2138:2149 Visual version of the model shows that spatial structure is a key factor, which helps bacteria to survive and to adapt to changed environmental conditions. 26894828 15 30 theme spatial 2117:2123 arg1 structure 2125:2133 spatial structure 2117:2133 spatial structure 2117:2133 Visual version of the model shows that spatial structure is a key factor, which helps bacteria to survive and to adapt to changed environmental conditions. 26894828 0 31 theme Agent 0:4 arg1 Modeling 12:19 Agent Based Modeling 0:19 Agent Based Modeling of Human Gut 0:32 Agent Based Modeling of Human Gut Microbiome Interactions and Perturbations. 26894828 4 32 theme bacterial 590:598 arg1 species 600:606 new bacterial species 586:606 new bacterial species 586:606 Studies of the microbiome can provide insight on methods of improving health, including specific clinical procedures for individual microbial community composition modification and microbiota correction by colonizing with new bacterial species or dietary changes. 26894828 5 33 theme agent-based 685:695 arg1 model 697:701 an agent-based model 682:701 an agent-based model of interactions between two bacterial species and between species and the gut 682:779 METHODOLOGY/PRINCIPAL FINDINGS In this work we report an agent-based model of interactions between two bacterial species and between species and the gut. 26894828 6 34 theme bacterial 825:833 arg1 fermentation 835:846 bacterial fermentation 825:846 bacterial fermentation of polysaccharides to acetate and propionate 825:891 The model is based on reactions describing bacterial fermentation of polysaccharides to acetate and propionate and fermentation of acetate to butyrate. 26894828 15 35 theme model 2100:2104 arg1 version 2085:2091 Visual version 2078:2091 Visual version of the model 2078:2104 Visual version of the model shows that spatial structure is a key factor, which helps bacteria to survive and to adapt to changed environmental conditions. 26894828 10 36 theme sensitive 1387:1395 arg1 ratio 1378:1382 this suggestion ratio 1362:1382 this suggestion ratio of sensitive to resistant bacteria 1362:1417 The ability to mutate was considered to be a stochastic process, under this suggestion ratio of sensitive to resistant bacteria was calculated during antibiotic therapy and recovery. 26894828 14 37 theme bacterial 1929:1937 arg1 species 1939:1945 bacterial species 1929:1945 bacterial species 1929:1945 The model demonstrates not only quantitative dynamics of bacterial species, but also gives an ability to observe the emergent spatial structure and its alteration, depending on various feedback mechanisms. 26894828 4 38 theme new 586:588 arg1 species 600:606 new bacterial species 586:606 new bacterial species 586:606 Studies of the microbiome can provide insight on methods of improving health, including specific clinical procedures for individual microbial community composition modification and microbiota correction by colonizing with new bacterial species or dietary changes. 26894828 3 39 theme interactions 278:289 arg1 Examination 237:247 Examination 237:247 Examination of the intestinal microbiome interactions 237:289 Examination of the intestinal microbiome interactions is required for understanding of the community influence on host health. 26894828 4 40 theme microbiome 379:388 arg1 Studies 364:370 Studies 364:370 Studies of the microbiome 364:388 Studies of the microbiome can provide insight on methods of improving health, including specific clinical procedures for individual microbial community composition modification and microbiota correction by colonizing with new bacterial species or dietary changes. 26894828 14 41 theme emergent 1989:1996 arg1 structure 2006:2014 the emergent spatial structure 1985:2014 the emergent spatial structure 1985:2014 The model demonstrates not only quantitative dynamics of bacterial species, but also gives an ability to observe the emergent spatial structure and its alteration, depending on various feedback mechanisms. 26894828 7 42 used used 992:995 arg2 factor 981:986 disturbance factor 969:986 disturbance factor 969:986 Antibiotic treatment was chosen as disturbance factor and used to investigate stability of the system. 26894828 7 42 used used 992:995 arg2 treatment 945:953 Antibiotic treatment 934:953 Antibiotic treatment 934:953 Antibiotic treatment was chosen as disturbance factor and used to investigate stability of the system. 26894828 12 43 theme High 1639:1642 arg1 fraction 1644:1651 High fraction 1639:1651 High fraction of bacterial community 1639:1674 High fraction of bacterial community was shown to mutate during antibiotic treatment, though sensitive strains could become dominating after recovery. 26894828 15 44 theme key 2140:2142 arg1 factor 2144:2149 a key factor 2138:2149 a key factor 2138:2149 Visual version of the model shows that spatial structure is a key factor, which helps bacteria to survive and to adapt to changed environmental conditions. 26894828 15 44 theme key 2140:2142 arg1 structure 2125:2133 spatial structure 2117:2133 spatial structure 2117:2133 Visual version of the model shows that spatial structure is a key factor, which helps bacteria to survive and to adapt to changed environmental conditions. 26894828 4 45 theme specific 452:459 arg1 procedures 470:479 specific clinical procedures 452:479 specific clinical procedures for individual microbial community composition modification and microbiota correction 452:565 Studies of the microbiome can provide insight on methods of improving health, including specific clinical procedures for individual microbial community composition modification and microbiota correction by colonizing with new bacterial species or dietary changes. 26894828 0 46 theme Gut 30:32 arg1 Modeling 12:19 Agent Based Modeling 0:19 Agent Based Modeling of Human Gut 0:32 Agent Based Modeling of Human Gut Microbiome Interactions and Perturbations. 26894828 8 47 from dependence 1096:1105 arg1 quantity 1110:1117 quantity 1110:1117 quantity of feedback interactions inside the community, therapy duration and amount of antibiotics 1110:1207 System recovery after antibiotic treatment was analyzed as dependence on quantity of feedback interactions inside the community, therapy duration and amount of antibiotics. 26894828 3 48 theme intestinal 256:265 arg1 interactions 278:289 the intestinal microbiome interactions 252:289 the intestinal microbiome interactions 252:289 Examination of the intestinal microbiome interactions is required for understanding of the community influence on host health. 26894828 3 49 from health 356:361 arg1 understanding 307:319 understanding 307:319 understanding of the community influence on host health 307:361 Examination of the intestinal microbiome interactions is required for understanding of the community influence on host health. 26894828 10 50 theme suggestion 1367:1376 arg1 ratio 1378:1382 this suggestion ratio 1362:1382 this suggestion ratio of sensitive to resistant bacteria 1362:1417 The ability to mutate was considered to be a stochastic process, under this suggestion ratio of sensitive to resistant bacteria was calculated during antibiotic therapy and recovery. 26894828 0 51 theme Human 24:28 arg1 Gut 30:32 Human Gut 24:32 Human Gut 24:32 Agent Based Modeling of Human Gut Microbiome Interactions and Perturbations. 26894828 3 52 theme microbiome 267:276 arg1 interactions 278:289 the intestinal microbiome interactions 252:289 the intestinal microbiome interactions 252:289 Examination of the intestinal microbiome interactions is required for understanding of the community influence on host health. 26894828 10 53 dep ability 1295:1301 arg1 mutate 1306:1311 mutate 1306:1311 to mutate 1303:1311 The ability to mutate was considered to be a stochastic process, under this suggestion ratio of sensitive to resistant bacteria was calculated during antibiotic therapy and recovery. 26894828 2 54 theme external 217:224 arg1 pathogens 226:234 external pathogens 217:234 external pathogens 217:234 It is involved in the digestion and protects the host against external pathogens. 26894828 12 55 theme antibiotic 1703:1712 arg1 treatment 1714:1722 antibiotic treatment 1703:1722 antibiotic treatment 1703:1722 High fraction of bacterial community was shown to mutate during antibiotic treatment, though sensitive strains could become dominating after recovery. 26894828 13 56 theme resistance 1860:1869 arg1 cost 1848:1851 fitness cost 1840:1851 fitness cost of the resistance 1840:1869 The recovery of sensitive strains is explained by fitness cost of the resistance. 26894828 4 57 theme clinical 461:468 arg1 procedures 470:479 specific clinical procedures 452:479 specific clinical procedures for individual microbial community composition modification and microbiota correction 452:565 Studies of the microbiome can provide insight on methods of improving health, including specific clinical procedures for individual microbial community composition modification and microbiota correction by colonizing with new bacterial species or dietary changes. 26894828 15 58 theme environmental 2208:2220 arg1 conditions 2222:2231 changed environmental conditions 2200:2231 changed environmental conditions 2200:2231 Visual version of the model shows that spatial structure is a key factor, which helps bacteria to survive and to adapt to changed environmental conditions. 26894828 9 59 theme Bacterial 1210:1218 arg1 species 1220:1226 Bacterial species 1210:1226 Bacterial species 1210:1226 Bacterial species are known to mutate and acquire resistance to the antibiotics. 26894828 1 60 theme important 119:127 arg1 role 129:132 an important role 116:132 an important role 116:132 BACKGROUND Intestinal microbiota plays an important role in the human health. 26894828 8 61 theme therapy 1166:1172 arg1 duration 1174:1181 therapy duration 1166:1181 therapy duration 1166:1181 System recovery after antibiotic treatment was analyzed as dependence on quantity of feedback interactions inside the community, therapy duration and amount of antibiotics. 26894828 14 62 theme quantitative 1904:1915 arg1 dynamics 1917:1924 not only quantitative dynamics 1895:1924 not only quantitative dynamics of bacterial species 1895:1945 The model demonstrates not only quantitative dynamics of bacterial species, but also gives an ability to observe the emergent spatial structure and its alteration, depending on various feedback mechanisms. 26894828 5 63 theme bacterial 731:739 arg1 species 741:747 two bacterial species 727:747 two bacterial species 727:747 METHODOLOGY/PRINCIPAL FINDINGS In this work we report an agent-based model of interactions between two bacterial species and between species and the gut. 26894828 13 64 theme sensitive 1806:1814 arg1 strains 1816:1822 sensitive strains 1806:1822 sensitive strains 1806:1822 The recovery of sensitive strains is explained by fitness cost of the resistance. 26894828 10 65 theme resistant 1400:1408 arg1 bacteria 1410:1417 resistant bacteria 1400:1417 resistant bacteria 1400:1417 The ability to mutate was considered to be a stochastic process, under this suggestion ratio of sensitive to resistant bacteria was calculated during antibiotic therapy and recovery. 26894828 13 66 theme fitness 1840:1846 arg1 cost 1848:1851 fitness cost 1840:1851 fitness cost of the resistance 1840:1869 The recovery of sensitive strains is explained by fitness cost of the resistance. 26894828 4 67 dep composition 516:526 arg1 modification 528:539 modification 528:539 modification 528:539 Studies of the microbiome can provide insight on methods of improving health, including specific clinical procedures for individual microbial community composition modification and microbiota correction by colonizing with new bacterial species or dietary changes. 26894828 8 68 theme antibiotics 1197:1207 arg1 amount 1187:1192 amount 1187:1192 amount 1187:1192 System recovery after antibiotic treatment was analyzed as dependence on quantity of feedback interactions inside the community, therapy duration and amount of antibiotics. 26894828 8 68 theme antibiotics 1197:1207 arg1 community 1155:1163 the community 1151:1163 the community 1151:1163 System recovery after antibiotic treatment was analyzed as dependence on quantity of feedback interactions inside the community, therapy duration and amount of antibiotics. 26894828 8 68 theme antibiotics 1197:1207 arg1 duration 1174:1181 therapy duration 1166:1181 therapy duration 1166:1181 System recovery after antibiotic treatment was analyzed as dependence on quantity of feedback interactions inside the community, therapy duration and amount of antibiotics. 26894828 8 68 theme antibiotics 1197:1207 arg1 antibiotics 1197:1207 antibiotics 1197:1207 antibiotics 1197:1207 System recovery after antibiotic treatment was analyzed as dependence on quantity of feedback interactions inside the community, therapy duration and amount of antibiotics. 26894828 3 69 from influence 338:346 arg1 health 356:361 host health 351:361 host health 351:361 Examination of the intestinal microbiome interactions is required for understanding of the community influence on host health. 26894828 15 70 theme changed 2200:2206 arg1 conditions 2222:2231 changed environmental conditions 2200:2231 changed environmental conditions 2200:2231 Visual version of the model shows that spatial structure is a key factor, which helps bacteria to survive and to adapt to changed environmental conditions. 26894828 5 71 dep FINDINGS 650:657 arg1 we 672:673 we 672:673 we 672:673 METHODOLOGY/PRINCIPAL FINDINGS In this work we report an agent-based model of interactions between two bacterial species and between species and the gut. 26894828 12 72 theme community 1666:1674 arg1 fraction 1644:1651 High fraction 1639:1651 High fraction of bacterial community 1639:1674 High fraction of bacterial community was shown to mutate during antibiotic treatment, though sensitive strains could become dominating after recovery. 26894828 3 73 theme influence 338:346 arg1 understanding 307:319 understanding 307:319 understanding of the community influence on host health 307:361 Examination of the intestinal microbiome interactions is required for understanding of the community influence on host health. 26894828 14 74 theme spatial 1998:2004 arg1 structure 2006:2014 the emergent spatial structure 1985:2014 the emergent spatial structure 1985:2014 The model demonstrates not only quantitative dynamics of bacterial species, but also gives an ability to observe the emergent spatial structure and its alteration, depending on various feedback mechanisms. 26894828 14 75 theme feedback 2057:2064 arg1 mechanisms 2066:2075 various feedback mechanisms 2049:2075 various feedback mechanisms 2049:2075 The model demonstrates not only quantitative dynamics of bacterial species, but also gives an ability to observe the emergent spatial structure and its alteration, depending on various feedback mechanisms. 26894828 10 76 theme antibiotic 1441:1450 arg1 therapy 1452:1458 antibiotic therapy 1441:1458 antibiotic therapy 1441:1458 The ability to mutate was considered to be a stochastic process, under this suggestion ratio of sensitive to resistant bacteria was calculated during antibiotic therapy and recovery. 26894828 1 77 theme human 141:145 arg1 health 147:152 the human health 137:152 the human health 137:152 BACKGROUND Intestinal microbiota plays an important role in the human health. 26894828 7 78 theme disturbance 969:979 arg1 factor 981:986 disturbance factor 969:986 disturbance factor 969:986 Antibiotic treatment was chosen as disturbance factor and used to investigate stability of the system. 26894828 7 78 theme disturbance 969:979 arg1 treatment 945:953 Antibiotic treatment 934:953 Antibiotic treatment 934:953 Antibiotic treatment was chosen as disturbance factor and used to investigate stability of the system. 26894828 3 79 from understanding 307:319 arg1 health 356:361 host health 351:361 host health 351:361 Examination of the intestinal microbiome interactions is required for understanding of the community influence on host health. 26894828 15 80 theme Visual 2078:2083 arg1 version 2085:2091 Visual version 2078:2091 Visual version of the model 2078:2104 Visual version of the model shows that spatial structure is a key factor, which helps bacteria to survive and to adapt to changed environmental conditions. 26894828 14 81 theme various 2049:2055 arg1 mechanisms 2066:2075 various feedback mechanisms 2049:2075 various feedback mechanisms 2049:2075 The model demonstrates not only quantitative dynamics of bacterial species, but also gives an ability to observe the emergent spatial structure and its alteration, depending on various feedback mechanisms. 26894828 10 82 theme stochastic 1336:1345 arg1 process 1347:1353 a stochastic process 1334:1353 a stochastic process 1334:1353 The ability to mutate was considered to be a stochastic process, under this suggestion ratio of sensitive to resistant bacteria was calculated during antibiotic therapy and recovery. 26894828 10 82 theme stochastic 1336:1345 arg1 ability 1295:1301 The ability 1291:1301 The ability to mutate 1291:1311 The ability to mutate was considered to be a stochastic process, under this suggestion ratio of sensitive to resistant bacteria was calculated during antibiotic therapy and recovery. 24693882 14 0 theme liquors 2583:2589 arg1 approaches 2530:2539 novel alkali recovery approaches 2508:2539 novel alkali recovery approaches 2508:2539 This pretreatment approach allows for many possible process configurations involving novel alkali recovery approaches and novel uses of alkaline pre-extraction liquors. 24693882 2 1 theme alkaline 391:398 arg1 pre-extraction 400:413 alkaline pre-extraction 391:413 alkaline pre-extraction 391:413 We propose that conventional one-stage AHP pretreatment can be improved using alkaline pre-extraction, which requires significantly less H2O2 and NaOH. 24693882 15 2 theme water 2776:2780 arg1 use 2782:2784 water use 2776:2784 water use 2776:2784 Further work is required to identify the most economical configuration, including process designs using techno-economic analysis and investigating processing strategies that economize water use. 24693882 9 3 theme liquors 1459:1465 arg1 screening 1389:1397 ELISA screening 1383:1397 ELISA screening of alkali pre-extraction liquors and the AHP post-treatment liquors 1383:1465 ELISA screening of alkali pre-extraction liquors and the AHP post-treatment liquors demonstrated that xyloglucan and β-glucans likely remained tightly bound in the biomass whereas the majority of the soluble polymeric xylans were glucurono (arabino) xylans and potentially homoxylans. 24693882 14 4 theme alkaline 2559:2566 arg1 liquors 2583:2589 alkaline pre-extraction liquors 2559:2589 alkaline pre-extraction liquors 2559:2589 This pretreatment approach allows for many possible process configurations involving novel alkali recovery approaches and novel uses of alkaline pre-extraction liquors. 24693882 13 5 theme corn 2314:2317 arg1 stover 2319:2324 pretreated corn stover 2303:2324 pretreated corn stover using substantially lower oxidant loadings 2303:2367 This approach achieved high enzymatic sugars yields from pretreated corn stover using substantially lower oxidant loadings than have been reported previously in the literature. 24693882 8 6 theme AHP 1215:1217 arg1 post-treatment 1219:1232 AHP post-treatment 1215:1232 AHP post-treatment at low oxidant loading (25 mg H2O2 per g pre-extracted biomass) 1215:1296 AHP post-treatment at low oxidant loading (25 mg H2O2 per g pre-extracted biomass) increased glucose hydrolysis yields by 5%, which approached near-theoretical yields. 24693882 10 7 theme Pectic 1668:1673 arg1 polysaccharides 1675:1689 Pectic polysaccharides 1668:1689 Pectic polysaccharides 1668:1689 Pectic polysaccharides were depleted in the AHP post-treatment liquor relative to the alkaline pre-extraction liquor. 24693882 3 8 theme alkaline 587:594 arg1 pre-extraction 596:609 alkaline pre-extraction 587:609 alkaline pre-extraction 587:609 To better understand the potential of this approach, this study investigates several components of this process including alkaline pre-extraction, alkaline and alkaline-oxidative post-treatment, fermentation, and the composition of alkali extracts. 24693882 8 9 from loading 1249:1255 arg1 post-treatment 1219:1232 AHP post-treatment 1215:1232 AHP post-treatment at low oxidant loading (25 mg H2O2 per g pre-extracted biomass) 1215:1296 AHP post-treatment at low oxidant loading (25 mg H2O2 per g pre-extracted biomass) increased glucose hydrolysis yields by 5%, which approached near-theoretical yields. 24693882 8 10 theme pre-extracted 1275:1287 arg1 biomass 1289:1295 g pre-extracted biomass 1273:1295 g pre-extracted biomass 1273:1295 AHP post-treatment at low oxidant loading (25 mg H2O2 per g pre-extracted biomass) increased glucose hydrolysis yields by 5%, which approached near-theoretical yields. 24693882 2 11 theme AHP 352:354 arg1 pretreatment 356:367 conventional one-stage AHP pretreatment 329:367 conventional one-stage AHP pretreatment 329:367 We propose that conventional one-stage AHP pretreatment can be improved using alkaline pre-extraction, which requires significantly less H2O2 and NaOH. 24693882 5 12 theme strong 931:936 arg1 susceptibility 938:951 a strong susceptibility 929:951 a strong susceptibility to drying-induced hydrolysis yield losses 929:993 The resulting substrates were highly digestible by cellulolytic enzymes at relatively low enzyme loadings and had a strong susceptibility to drying-induced hydrolysis yield losses. 24693882 8 13 theme oxidant 1241:1247 arg1 loading 1249:1255 low oxidant loading 1237:1255 low oxidant loading (25 mg H2O2 per g pre-extracted biomass) 1237:1296 AHP post-treatment at low oxidant loading (25 mg H2O2 per g pre-extracted biomass) increased glucose hydrolysis yields by 5%, which approached near-theoretical yields. 24693882 2 14 theme conventional 329:340 arg1 pretreatment 356:367 conventional one-stage AHP pretreatment 329:367 conventional one-stage AHP pretreatment 329:367 We propose that conventional one-stage AHP pretreatment can be improved using alkaline pre-extraction, which requires significantly less H2O2 and NaOH. 24693882 5 15 theme low 901:903 arg1 loadings 912:919 relatively low enzyme loadings 890:919 relatively low enzyme loadings 890:919 The resulting substrates were highly digestible by cellulolytic enzymes at relatively low enzyme loadings and had a strong susceptibility to drying-induced hydrolysis yield losses. 24693882 4 16 theme Mild 722:725 arg1 pre-extraction 732:745 Mild NaOH pre-extraction 722:745 Mild NaOH pre-extraction of corn stover 722:760 RESULTS Mild NaOH pre-extraction of corn stover uses less than 0.1 g NaOH per g corn stover at 80°C. 24693882 11 17 theme two-stage 1917:1925 arg1 pretreatment 1927:1938 this two-stage pretreatment 1912:1938 this two-stage pretreatment 1912:1938 Because the already-low inhibitor content was further decreased in the alkaline pre-extraction, the hydrolysates generated by this two-stage pretreatment were highly fermentable by Saccharomyces cerevisiae strains that were metabolically engineered and evolved for xylose fermentation. 24693882 13 18 theme enzymatic 2274:2282 arg1 yields 2291:2296 high enzymatic sugars yields 2269:2296 high enzymatic sugars yields from pretreated corn stover using substantially lower oxidant loadings 2269:2367 This approach achieved high enzymatic sugars yields from pretreated corn stover using substantially lower oxidant loadings than have been reported previously in the literature. 24693882 8 19 theme mg 1261:1262 arg1 H2O2 1264:1267 25 mg H2O2 1258:1267 25 mg H2O2 per g pre-extracted biomass 1258:1295 AHP post-treatment at low oxidant loading (25 mg H2O2 per g pre-extracted biomass) increased glucose hydrolysis yields by 5%, which approached near-theoretical yields. 24693882 4 20 theme g 781:781 arg1 stover 799:804 less than 0.1 g NaOH per g corn stover 767:804 less than 0.1 g NaOH per g corn stover at 80°C 767:812 RESULTS Mild NaOH pre-extraction of corn stover uses less than 0.1 g NaOH per g corn stover at 80°C. 24693882 7 21 dep 0.10 1163:1166 arg1 to 1160:1161 to 1160:1161 to 1160:1161 During alkaline pre-extraction, up to 0.10 g of alkali was consumed per g of corn stover. 24693882 4 22 theme per 788:790 arg1 stover 799:804 less than 0.1 g NaOH per g corn stover 767:804 less than 0.1 g NaOH per g corn stover at 80°C 767:812 RESULTS Mild NaOH pre-extraction of corn stover uses less than 0.1 g NaOH per g corn stover at 80°C. 24693882 14 23 theme alkali 2514:2519 arg1 approaches 2530:2539 novel alkali recovery approaches 2508:2539 novel alkali recovery approaches 2508:2539 This pretreatment approach allows for many possible process configurations involving novel alkali recovery approaches and novel uses of alkaline pre-extraction liquors. 24693882 3 24 theme alkali 697:702 arg1 extracts 704:711 alkali extracts 697:711 alkali extracts 697:711 To better understand the potential of this approach, this study investigates several components of this process including alkaline pre-extraction, alkaline and alkaline-oxidative post-treatment, fermentation, and the composition of alkali extracts. 24693882 1 25 theme chemical 162:169 arg1 pretreatment 171:182 A two-stage chemical pretreatment 150:182 A two-stage chemical pretreatment of corn stover 150:197 BACKGROUND A two-stage chemical pretreatment of corn stover is investigated comprising an NaOH pre-extraction followed by an alkaline hydrogen peroxide (AHP) post-treatment. 24693882 11 26 theme xylose 2051:2056 arg1 fermentation 2058:2069 xylose fermentation 2051:2069 xylose fermentation 2051:2069 Because the already-low inhibitor content was further decreased in the alkaline pre-extraction, the hydrolysates generated by this two-stage pretreatment were highly fermentable by Saccharomyces cerevisiae strains that were metabolically engineered and evolved for xylose fermentation. 24693882 12 27 theme fermentable 2196:2206 arg1 sugars 2208:2213 fermentable sugars 2196:2213 fermentable sugars 2196:2213 CONCLUSIONS This work demonstrates that this two-stage pretreatment process is well suited for converting lignocellulose to fermentable sugars and biofuels, such as ethanol. 24693882 12 27 theme fermentable 2196:2206 arg1 ethanol 2237:2243 ethanol 2237:2243 ethanol 2237:2243 CONCLUSIONS This work demonstrates that this two-stage pretreatment process is well suited for converting lignocellulose to fermentable sugars and biofuels, such as ethanol. 24693882 0 28 theme stover 80:85 arg1 post-treatment 57:70 alkaline-oxidative post-treatment 38:70 alkaline-oxidative post-treatment of corn stover 38:85 Coupling alkaline pre-extraction with alkaline-oxidative post-treatment of corn stover to enhance enzymatic hydrolysis and fermentability. 24693882 14 29 theme process 2475:2481 arg1 configurations 2483:2496 many possible process configurations 2461:2496 many possible process configurations involving novel alkali recovery approaches and novel uses of alkaline pre-extraction liquors 2461:2589 This pretreatment approach allows for many possible process configurations involving novel alkali recovery approaches and novel uses of alkaline pre-extraction liquors. 24693882 11 30 theme alkaline 1857:1864 arg1 pre-extraction 1866:1879 the alkaline pre-extraction 1853:1879 the alkaline pre-extraction 1853:1879 Because the already-low inhibitor content was further decreased in the alkaline pre-extraction, the hydrolysates generated by this two-stage pretreatment were highly fermentable by Saccharomyces cerevisiae strains that were metabolically engineered and evolved for xylose fermentation. 24693882 5 31 theme resulting 819:827 arg1 substrates 829:838 The resulting substrates 815:838 The resulting substrates 815:838 The resulting substrates were highly digestible by cellulolytic enzymes at relatively low enzyme loadings and had a strong susceptibility to drying-induced hydrolysis yield losses. 24693882 5 31 theme resulting 819:827 arg1 digestible 852:861 digestible 852:861 digestible 852:861 The resulting substrates were highly digestible by cellulolytic enzymes at relatively low enzyme loadings and had a strong susceptibility to drying-induced hydrolysis yield losses. 24693882 5 32 theme hydrolysis 971:980 arg1 losses 988:993 drying-induced hydrolysis yield losses 956:993 drying-induced hydrolysis yield losses 956:993 The resulting substrates were highly digestible by cellulolytic enzymes at relatively low enzyme loadings and had a strong susceptibility to drying-induced hydrolysis yield losses. 24693882 12 33 dep CONCLUSIONS 2072:2082 arg1 demonstrates 2094:2105 demonstrates 2094:2105 demonstrates that this two-stage pretreatment process is well suited for converting lignocellulose to fermentable sugars and biofuels, such as ethanol 2094:2243 CONCLUSIONS This work demonstrates that this two-stage pretreatment process is well suited for converting lignocellulose to fermentable sugars and biofuels, such as ethanol. 24693882 14 34 theme many 2461:2464 arg1 configurations 2483:2496 many possible process configurations 2461:2496 many possible process configurations involving novel alkali recovery approaches and novel uses of alkaline pre-extraction liquors 2461:2589 This pretreatment approach allows for many possible process configurations involving novel alkali recovery approaches and novel uses of alkaline pre-extraction liquors. 24693882 15 35 theme processing 2739:2748 arg1 strategies 2750:2759 processing strategies 2739:2759 processing strategies that economize water use 2739:2784 Further work is required to identify the most economical configuration, including process designs using techno-economic analysis and investigating processing strategies that economize water use. 24693882 8 36 dep increased 1298:1306 arg1 approached 1347:1356 approached 1347:1356 approached near-theoretical yields 1347:1380 AHP post-treatment at low oxidant loading (25 mg H2O2 per g pre-extracted biomass) increased glucose hydrolysis yields by 5%, which approached near-theoretical yields. 24693882 6 37 theme xylan 1065:1069 arg1 removal 1071:1077 xylan removal 1065:1077 xylan removal 1065:1077 Alkaline pre-extraction was highly selective for lignin removal over xylan removal; xylan removal was relatively minimal (~20%). 24693882 14 38 dep novel 2545:2549 arg1 uses 2551:2554 uses 2551:2554 uses 2551:2554 This pretreatment approach allows for many possible process configurations involving novel alkali recovery approaches and novel uses of alkaline pre-extraction liquors. 24693882 1 39 dep BACKGROUND 139:148 arg1 investigated 202:213 investigated 202:213 is investigated comprising an NaOH pre-extraction followed by an alkaline hydrogen peroxide (AHP) post-treatment 199:310 BACKGROUND A two-stage chemical pretreatment of corn stover is investigated comprising an NaOH pre-extraction followed by an alkaline hydrogen peroxide (AHP) post-treatment. 24693882 10 40 theme post-treatment 1716:1729 arg1 liquor 1731:1736 the AHP post-treatment liquor 1708:1736 the AHP post-treatment liquor relative to the alkaline pre-extraction liquor 1708:1783 Pectic polysaccharides were depleted in the AHP post-treatment liquor relative to the alkaline pre-extraction liquor. 24693882 9 41 theme glucurono 1613:1621 arg1 majority 1567:1574 the majority 1563:1574 the majority of the soluble polymeric xylans 1563:1606 ELISA screening of alkali pre-extraction liquors and the AHP post-treatment liquors demonstrated that xyloglucan and β-glucans likely remained tightly bound in the biomass whereas the majority of the soluble polymeric xylans were glucurono (arabino) xylans and potentially homoxylans. 24693882 9 41 theme glucurono 1613:1621 arg1 xylans 1633:1638 glucurono (arabino) xylans 1613:1638 glucurono (arabino) xylans 1613:1638 ELISA screening of alkali pre-extraction liquors and the AHP post-treatment liquors demonstrated that xyloglucan and β-glucans likely remained tightly bound in the biomass whereas the majority of the soluble polymeric xylans were glucurono (arabino) xylans and potentially homoxylans. 24693882 4 42 theme corn 794:797 arg1 stover 799:804 less than 0.1 g NaOH per g corn stover 767:804 less than 0.1 g NaOH per g corn stover at 80°C 767:812 RESULTS Mild NaOH pre-extraction of corn stover uses less than 0.1 g NaOH per g corn stover at 80°C. 24693882 14 43 theme pretreatment 2428:2439 arg1 approach 2441:2448 This pretreatment approach 2423:2448 This pretreatment approach 2423:2448 This pretreatment approach allows for many possible process configurations involving novel alkali recovery approaches and novel uses of alkaline pre-extraction liquors. 24693882 0 44 theme Coupling 0:7 arg1 pre-extraction 18:31 Coupling alkaline pre-extraction 0:31 Coupling alkaline pre-extraction with alkaline-oxidative post-treatment of corn stover 0:85 Coupling alkaline pre-extraction with alkaline-oxidative post-treatment of corn stover to enhance enzymatic hydrolysis and fermentability. 24693882 15 45 theme techno-economic 2696:2710 arg1 analysis 2712:2719 techno-economic analysis 2696:2719 techno-economic analysis 2696:2719 Further work is required to identify the most economical configuration, including process designs using techno-economic analysis and investigating processing strategies that economize water use. 24693882 9 46 theme arabino 1624:1630 arg1 majority 1567:1574 the majority 1563:1574 the majority of the soluble polymeric xylans 1563:1606 ELISA screening of alkali pre-extraction liquors and the AHP post-treatment liquors demonstrated that xyloglucan and β-glucans likely remained tightly bound in the biomass whereas the majority of the soluble polymeric xylans were glucurono (arabino) xylans and potentially homoxylans. 24693882 9 46 theme arabino 1624:1630 arg1 xylans 1633:1638 glucurono (arabino) xylans 1613:1638 glucurono (arabino) xylans 1613:1638 ELISA screening of alkali pre-extraction liquors and the AHP post-treatment liquors demonstrated that xyloglucan and β-glucans likely remained tightly bound in the biomass whereas the majority of the soluble polymeric xylans were glucurono (arabino) xylans and potentially homoxylans. 24693882 3 47 theme approach 508:515 arg1 potential 490:498 the potential 486:498 the potential of this approach 486:515 To better understand the potential of this approach, this study investigates several components of this process including alkaline pre-extraction, alkaline and alkaline-oxidative post-treatment, fermentation, and the composition of alkali extracts. 24693882 7 48 theme stover 1207:1212 arg1 g 1197:1197 g 1197:1197 g of corn stover 1197:1212 During alkaline pre-extraction, up to 0.10 g of alkali was consumed per g of corn stover. 24693882 13 49 theme lower 2346:2350 arg1 loadings 2360:2367 substantially lower oxidant loadings 2332:2367 substantially lower oxidant loadings 2332:2367 This approach achieved high enzymatic sugars yields from pretreated corn stover using substantially lower oxidant loadings than have been reported previously in the literature. 24693882 10 50 theme relative 1738:1745 arg1 liquor 1731:1736 the AHP post-treatment liquor 1708:1736 the AHP post-treatment liquor relative to the alkaline pre-extraction liquor 1708:1783 Pectic polysaccharides were depleted in the AHP post-treatment liquor relative to the alkaline pre-extraction liquor. 24693882 0 51 theme alkaline-oxidative 38:55 arg1 post-treatment 57:70 alkaline-oxidative post-treatment 38:70 alkaline-oxidative post-treatment of corn stover 38:85 Coupling alkaline pre-extraction with alkaline-oxidative post-treatment of corn stover to enhance enzymatic hydrolysis and fermentability. 24693882 13 52 theme oxidant 2352:2358 arg1 loadings 2360:2367 substantially lower oxidant loadings 2332:2367 substantially lower oxidant loadings 2332:2367 This approach achieved high enzymatic sugars yields from pretreated corn stover using substantially lower oxidant loadings than have been reported previously in the literature. 24693882 4 53 dep RESULTS 714:720 arg1 uses 762:765 uses 762:765 uses less than 0.1 g NaOH per g corn stover at 80°C 762:812 RESULTS Mild NaOH pre-extraction of corn stover uses less than 0.1 g NaOH per g corn stover at 80°C. 24693882 0 54 with pre-extraction 18:31 arg1 post-treatment 57:70 alkaline-oxidative post-treatment 38:70 alkaline-oxidative post-treatment of corn stover 38:85 Coupling alkaline pre-extraction with alkaline-oxidative post-treatment of corn stover to enhance enzymatic hydrolysis and fermentability. 24693882 9 55 theme alkali 1402:1407 arg1 liquors 1424:1430 alkali pre-extraction liquors 1402:1430 alkali pre-extraction liquors 1402:1430 ELISA screening of alkali pre-extraction liquors and the AHP post-treatment liquors demonstrated that xyloglucan and β-glucans likely remained tightly bound in the biomass whereas the majority of the soluble polymeric xylans were glucurono (arabino) xylans and potentially homoxylans. 24693882 13 56 from stover 2319:2324 arg1 yields 2291:2296 high enzymatic sugars yields 2269:2296 high enzymatic sugars yields from pretreated corn stover using substantially lower oxidant loadings 2269:2367 This approach achieved high enzymatic sugars yields from pretreated corn stover using substantially lower oxidant loadings than have been reported previously in the literature. 24693882 11 57 theme inhibitor 1810:1818 arg1 content 1820:1826 the already-low inhibitor content 1794:1826 the already-low inhibitor content 1794:1826 Because the already-low inhibitor content was further decreased in the alkaline pre-extraction, the hydrolysates generated by this two-stage pretreatment were highly fermentable by Saccharomyces cerevisiae strains that were metabolically engineered and evolved for xylose fermentation. 24693882 10 58 theme pre-extraction 1763:1776 arg1 liquor 1778:1783 the alkaline pre-extraction liquor 1750:1783 the alkaline pre-extraction liquor 1750:1783 Pectic polysaccharides were depleted in the AHP post-treatment liquor relative to the alkaline pre-extraction liquor. 24693882 9 59 theme liquors 1424:1430 arg1 screening 1389:1397 ELISA screening 1383:1397 ELISA screening of alkali pre-extraction liquors and the AHP post-treatment liquors 1383:1465 ELISA screening of alkali pre-extraction liquors and the AHP post-treatment liquors demonstrated that xyloglucan and β-glucans likely remained tightly bound in the biomass whereas the majority of the soluble polymeric xylans were glucurono (arabino) xylans and potentially homoxylans. 24693882 1 60 theme hydrogen 273:280 arg1 AHP 292:294 AHP 292:294 AHP 292:294 BACKGROUND A two-stage chemical pretreatment of corn stover is investigated comprising an NaOH pre-extraction followed by an alkaline hydrogen peroxide (AHP) post-treatment. 24693882 1 60 theme hydrogen 273:280 arg1 peroxide 282:289 alkaline hydrogen peroxide 264:289 an alkaline hydrogen peroxide (AHP) post-treatment 261:310 BACKGROUND A two-stage chemical pretreatment of corn stover is investigated comprising an NaOH pre-extraction followed by an alkaline hydrogen peroxide (AHP) post-treatment. 24693882 6 61 theme Alkaline 996:1003 arg1 pre-extraction 1005:1018 Alkaline pre-extraction 996:1018 Alkaline pre-extraction 996:1018 Alkaline pre-extraction was highly selective for lignin removal over xylan removal; xylan removal was relatively minimal (~20%). 24693882 7 62 theme alkali 1173:1178 arg1 g 1168:1168 up to 0.10 g 1157:1168 up to 0.10 g of alkali 1157:1178 During alkaline pre-extraction, up to 0.10 g of alkali was consumed per g of corn stover. 24693882 11 63 theme Saccharomyces 1967:1979 arg1 strains 1992:1998 Saccharomyces cerevisiae strains 1967:1998 Saccharomyces cerevisiae strains that were metabolically engineered and evolved for xylose fermentation 1967:2069 Because the already-low inhibitor content was further decreased in the alkaline pre-extraction, the hydrolysates generated by this two-stage pretreatment were highly fermentable by Saccharomyces cerevisiae strains that were metabolically engineered and evolved for xylose fermentation. 24693882 9 64 theme post-treatment 1444:1457 arg1 liquors 1459:1465 the AHP post-treatment liquors 1436:1465 the AHP post-treatment liquors 1436:1465 ELISA screening of alkali pre-extraction liquors and the AHP post-treatment liquors demonstrated that xyloglucan and β-glucans likely remained tightly bound in the biomass whereas the majority of the soluble polymeric xylans were glucurono (arabino) xylans and potentially homoxylans. 24693882 14 65 theme pre-extraction 2568:2581 arg1 liquors 2583:2589 alkaline pre-extraction liquors 2559:2589 alkaline pre-extraction liquors 2559:2589 This pretreatment approach allows for many possible process configurations involving novel alkali recovery approaches and novel uses of alkaline pre-extraction liquors. 24693882 13 66 theme pretreated 2303:2312 arg1 stover 2319:2324 pretreated corn stover 2303:2324 pretreated corn stover using substantially lower oxidant loadings 2303:2367 This approach achieved high enzymatic sugars yields from pretreated corn stover using substantially lower oxidant loadings than have been reported previously in the literature. 24693882 12 67 theme pretreatment 2127:2138 arg1 process 2140:2146 this two-stage pretreatment process 2112:2146 this two-stage pretreatment process 2112:2146 CONCLUSIONS This work demonstrates that this two-stage pretreatment process is well suited for converting lignocellulose to fermentable sugars and biofuels, such as ethanol. 24693882 5 68 theme drying-induced 956:969 arg1 losses 988:993 drying-induced hydrolysis yield losses 956:993 drying-induced hydrolysis yield losses 956:993 The resulting substrates were highly digestible by cellulolytic enzymes at relatively low enzyme loadings and had a strong susceptibility to drying-induced hydrolysis yield losses. 24693882 4 69 theme corn 750:753 arg1 stover 755:760 corn stover 750:760 corn stover 750:760 RESULTS Mild NaOH pre-extraction of corn stover uses less than 0.1 g NaOH per g corn stover at 80°C. 24693882 4 70 theme NaOH 727:730 arg1 pre-extraction 732:745 Mild NaOH pre-extraction 722:745 Mild NaOH pre-extraction of corn stover 722:760 RESULTS Mild NaOH pre-extraction of corn stover uses less than 0.1 g NaOH per g corn stover at 80°C. 24693882 3 71 theme alkaline-oxidative 625:642 arg1 post-treatment 644:657 alkaline and alkaline-oxidative post-treatment 612:657 post-treatment 644:657 To better understand the potential of this approach, this study investigates several components of this process including alkaline pre-extraction, alkaline and alkaline-oxidative post-treatment, fermentation, and the composition of alkali extracts. 24693882 8 72 theme g 1273:1273 arg1 biomass 1289:1295 g pre-extracted biomass 1273:1295 g pre-extracted biomass 1273:1295 AHP post-treatment at low oxidant loading (25 mg H2O2 per g pre-extracted biomass) increased glucose hydrolysis yields by 5%, which approached near-theoretical yields. 24693882 7 73 theme alkaline 1132:1139 arg1 pre-extraction 1141:1154 alkaline pre-extraction 1132:1154 alkaline pre-extraction 1132:1154 During alkaline pre-extraction, up to 0.10 g of alkali was consumed per g of corn stover. 24693882 2 74 theme one-stage 342:350 arg1 pretreatment 356:367 conventional one-stage AHP pretreatment 329:367 conventional one-stage AHP pretreatment 329:367 We propose that conventional one-stage AHP pretreatment can be improved using alkaline pre-extraction, which requires significantly less H2O2 and NaOH. 24693882 1 75 theme NaOH 229:232 arg1 pre-extraction 234:247 an NaOH pre-extraction 226:247 an NaOH pre-extraction followed by an alkaline hydrogen peroxide (AHP) post-treatment 226:310 BACKGROUND A two-stage chemical pretreatment of corn stover is investigated comprising an NaOH pre-extraction followed by an alkaline hydrogen peroxide (AHP) post-treatment. 24693882 8 76 theme low 1237:1239 arg1 loading 1249:1255 low oxidant loading 1237:1255 low oxidant loading (25 mg H2O2 per g pre-extracted biomass) 1237:1296 AHP post-treatment at low oxidant loading (25 mg H2O2 per g pre-extracted biomass) increased glucose hydrolysis yields by 5%, which approached near-theoretical yields. 24693882 6 77 theme lignin 1045:1050 arg1 removal 1052:1058 lignin removal 1045:1058 lignin removal 1045:1058 Alkaline pre-extraction was highly selective for lignin removal over xylan removal; xylan removal was relatively minimal (~20%). 24693882 1 78 theme stover 192:197 arg1 pretreatment 171:182 A two-stage chemical pretreatment 150:182 A two-stage chemical pretreatment of corn stover 150:197 BACKGROUND A two-stage chemical pretreatment of corn stover is investigated comprising an NaOH pre-extraction followed by an alkaline hydrogen peroxide (AHP) post-treatment. 24693882 9 79 theme soluble 1583:1589 arg1 xylans 1601:1606 the soluble polymeric xylans 1579:1606 the soluble polymeric xylans 1579:1606 ELISA screening of alkali pre-extraction liquors and the AHP post-treatment liquors demonstrated that xyloglucan and β-glucans likely remained tightly bound in the biomass whereas the majority of the soluble polymeric xylans were glucurono (arabino) xylans and potentially homoxylans. 24693882 13 80 theme high 2269:2272 arg1 yields 2291:2296 high enzymatic sugars yields 2269:2296 high enzymatic sugars yields from pretreated corn stover using substantially lower oxidant loadings 2269:2367 This approach achieved high enzymatic sugars yields from pretreated corn stover using substantially lower oxidant loadings than have been reported previously in the literature. 24693882 5 81 theme enzyme 905:910 arg1 loadings 912:919 relatively low enzyme loadings 890:919 relatively low enzyme loadings 890:919 The resulting substrates were highly digestible by cellulolytic enzymes at relatively low enzyme loadings and had a strong susceptibility to drying-induced hydrolysis yield losses. 24693882 12 82 theme two-stage 2117:2125 arg1 process 2140:2146 this two-stage pretreatment process 2112:2146 this two-stage pretreatment process 2112:2146 CONCLUSIONS This work demonstrates that this two-stage pretreatment process is well suited for converting lignocellulose to fermentable sugars and biofuels, such as ethanol. 24693882 13 83 theme sugars 2284:2289 arg1 yields 2291:2296 high enzymatic sugars yields 2269:2296 high enzymatic sugars yields from pretreated corn stover using substantially lower oxidant loadings 2269:2367 This approach achieved high enzymatic sugars yields from pretreated corn stover using substantially lower oxidant loadings than have been reported previously in the literature. 24693882 5 84 from loadings 912:919 arg1 substrates 829:838 The resulting substrates 815:838 The resulting substrates 815:838 The resulting substrates were highly digestible by cellulolytic enzymes at relatively low enzyme loadings and had a strong susceptibility to drying-induced hydrolysis yield losses. 24693882 5 84 from loadings 912:919 arg1 digestible 852:861 digestible 852:861 digestible 852:861 The resulting substrates were highly digestible by cellulolytic enzymes at relatively low enzyme loadings and had a strong susceptibility to drying-induced hydrolysis yield losses. 24693882 5 85 theme yield 982:986 arg1 losses 988:993 drying-induced hydrolysis yield losses 956:993 drying-induced hydrolysis yield losses 956:993 The resulting substrates were highly digestible by cellulolytic enzymes at relatively low enzyme loadings and had a strong susceptibility to drying-induced hydrolysis yield losses. 24693882 8 86 theme 25 1258:1259 arg1 mg 1261:1262 mg 1261:1262 mg 1261:1262 AHP post-treatment at low oxidant loading (25 mg H2O2 per g pre-extracted biomass) increased glucose hydrolysis yields by 5%, which approached near-theoretical yields. 24693882 8 87 theme hydrolysis 1316:1325 arg1 yields 1327:1332 glucose hydrolysis yields 1308:1332 glucose hydrolysis yields 1308:1332 AHP post-treatment at low oxidant loading (25 mg H2O2 per g pre-extracted biomass) increased glucose hydrolysis yields by 5%, which approached near-theoretical yields. 24693882 14 88 theme recovery 2521:2528 arg1 approaches 2530:2539 novel alkali recovery approaches 2508:2539 novel alkali recovery approaches 2508:2539 This pretreatment approach allows for many possible process configurations involving novel alkali recovery approaches and novel uses of alkaline pre-extraction liquors. 24693882 15 89 theme process 2674:2680 arg1 designs 2682:2688 process designs 2674:2688 process designs using techno-economic analysis and investigating processing strategies that economize water use 2674:2784 Further work is required to identify the most economical configuration, including process designs using techno-economic analysis and investigating processing strategies that economize water use. 24693882 1 90 theme two-stage 152:160 arg1 pretreatment 171:182 A two-stage chemical pretreatment 150:182 A two-stage chemical pretreatment of corn stover 150:197 BACKGROUND A two-stage chemical pretreatment of corn stover is investigated comprising an NaOH pre-extraction followed by an alkaline hydrogen peroxide (AHP) post-treatment. 24693882 3 91 theme alkaline 612:619 arg1 post-treatment 644:657 alkaline and alkaline-oxidative post-treatment 612:657 post-treatment 644:657 To better understand the potential of this approach, this study investigates several components of this process including alkaline pre-extraction, alkaline and alkaline-oxidative post-treatment, fermentation, and the composition of alkali extracts. 24693882 4 92 theme NaOH 783:786 arg1 stover 799:804 less than 0.1 g NaOH per g corn stover 767:804 less than 0.1 g NaOH per g corn stover at 80°C 767:812 RESULTS Mild NaOH pre-extraction of corn stover uses less than 0.1 g NaOH per g corn stover at 80°C. 24693882 14 93 theme novel 2508:2512 arg1 approaches 2530:2539 novel alkali recovery approaches 2508:2539 novel alkali recovery approaches 2508:2539 This pretreatment approach allows for many possible process configurations involving novel alkali recovery approaches and novel uses of alkaline pre-extraction liquors. 24693882 4 94 theme stover 755:760 arg1 pre-extraction 732:745 Mild NaOH pre-extraction 722:745 Mild NaOH pre-extraction of corn stover 722:760 RESULTS Mild NaOH pre-extraction of corn stover uses less than 0.1 g NaOH per g corn stover at 80°C. 24693882 0 95 theme enzymatic 98:106 arg1 hydrolysis 108:117 enzymatic hydrolysis 98:117 enzymatic hydrolysis 98:117 Coupling alkaline pre-extraction with alkaline-oxidative post-treatment of corn stover to enhance enzymatic hydrolysis and fermentability. 24693882 11 96 theme cerevisiae 1981:1990 arg1 strains 1992:1998 Saccharomyces cerevisiae strains 1967:1998 Saccharomyces cerevisiae strains that were metabolically engineered and evolved for xylose fermentation 1967:2069 Because the already-low inhibitor content was further decreased in the alkaline pre-extraction, the hydrolysates generated by this two-stage pretreatment were highly fermentable by Saccharomyces cerevisiae strains that were metabolically engineered and evolved for xylose fermentation. 24693882 15 97 theme economical 2638:2647 arg1 configuration 2649:2661 the most economical configuration 2629:2661 the most economical configuration 2629:2661 Further work is required to identify the most economical configuration, including process designs using techno-economic analysis and investigating processing strategies that economize water use. 24693882 1 98 theme corn 187:190 arg1 stover 192:197 corn stover 187:197 corn stover 187:197 BACKGROUND A two-stage chemical pretreatment of corn stover is investigated comprising an NaOH pre-extraction followed by an alkaline hydrogen peroxide (AHP) post-treatment. 24693882 6 99 theme xylan 1080:1084 arg1 removal 1086:1092 xylan removal 1080:1092 xylan removal 1080:1092 Alkaline pre-extraction was highly selective for lignin removal over xylan removal; xylan removal was relatively minimal (~20%). 24693882 14 100 theme possible 2466:2473 arg1 configurations 2483:2496 many possible process configurations 2461:2496 many possible process configurations involving novel alkali recovery approaches and novel uses of alkaline pre-extraction liquors 2461:2589 This pretreatment approach allows for many possible process configurations involving novel alkali recovery approaches and novel uses of alkaline pre-extraction liquors. 24693882 9 101 theme polymeric 1591:1599 arg1 xylans 1601:1606 the soluble polymeric xylans 1579:1606 the soluble polymeric xylans 1579:1606 ELISA screening of alkali pre-extraction liquors and the AHP post-treatment liquors demonstrated that xyloglucan and β-glucans likely remained tightly bound in the biomass whereas the majority of the soluble polymeric xylans were glucurono (arabino) xylans and potentially homoxylans. 24693882 9 102 theme xylans 1601:1606 arg1 majority 1567:1574 the majority 1563:1574 the majority of the soluble polymeric xylans 1563:1606 ELISA screening of alkali pre-extraction liquors and the AHP post-treatment liquors demonstrated that xyloglucan and β-glucans likely remained tightly bound in the biomass whereas the majority of the soluble polymeric xylans were glucurono (arabino) xylans and potentially homoxylans. 24693882 9 102 theme xylans 1601:1606 arg1 xylans 1633:1638 glucurono (arabino) xylans 1613:1638 glucurono (arabino) xylans 1613:1638 ELISA screening of alkali pre-extraction liquors and the AHP post-treatment liquors demonstrated that xyloglucan and β-glucans likely remained tightly bound in the biomass whereas the majority of the soluble polymeric xylans were glucurono (arabino) xylans and potentially homoxylans. 24693882 5 103 contain had 925:927 arg2 susceptibility 938:951 a strong susceptibility 929:951 a strong susceptibility to drying-induced hydrolysis yield losses 929:993 The resulting substrates were highly digestible by cellulolytic enzymes at relatively low enzyme loadings and had a strong susceptibility to drying-induced hydrolysis yield losses. 24693882 5 103 contain had 925:927 arg1 substrates 829:838 The resulting substrates 815:838 The resulting substrates 815:838 The resulting substrates were highly digestible by cellulolytic enzymes at relatively low enzyme loadings and had a strong susceptibility to drying-induced hydrolysis yield losses. 24693882 5 103 contain had 925:927 arg1 digestible 852:861 digestible 852:861 digestible 852:861 The resulting substrates were highly digestible by cellulolytic enzymes at relatively low enzyme loadings and had a strong susceptibility to drying-induced hydrolysis yield losses. 24693882 8 104 theme near-theoretical 1358:1373 arg1 yields 1375:1380 near-theoretical yields 1358:1380 near-theoretical yields 1358:1380 AHP post-treatment at low oxidant loading (25 mg H2O2 per g pre-extracted biomass) increased glucose hydrolysis yields by 5%, which approached near-theoretical yields. 24693882 4 105 from 80°C 809:812 arg1 stover 799:804 less than 0.1 g NaOH per g corn stover 767:804 less than 0.1 g NaOH per g corn stover at 80°C 767:812 RESULTS Mild NaOH pre-extraction of corn stover uses less than 0.1 g NaOH per g corn stover at 80°C. 24693882 6 106 dep minimal 1109:1115 arg1 % 1121:1121 ~20% 1118:1121 ~20% 1118:1121 Alkaline pre-extraction was highly selective for lignin removal over xylan removal; xylan removal was relatively minimal (~20%). 24693882 15 107 dep designs 2682:2688 arg1 investigating 2725:2737 investigating 2725:2737 investigating processing strategies that economize water use 2725:2784 Further work is required to identify the most economical configuration, including process designs using techno-economic analysis and investigating processing strategies that economize water use. 24693882 15 107 dep designs 2682:2688 arg1 using 2690:2694 using 2690:2694 using techno-economic analysis 2690:2719 Further work is required to identify the most economical configuration, including process designs using techno-economic analysis and investigating processing strategies that economize water use. 24693882 2 108 theme less 445:448 arg1 H2O2 450:453 H2O2 450:453 H2O2 450:453 We propose that conventional one-stage AHP pretreatment can be improved using alkaline pre-extraction, which requires significantly less H2O2 and NaOH. 24693882 0 109 theme alkaline 9:16 arg1 pre-extraction 18:31 Coupling alkaline pre-extraction 0:31 Coupling alkaline pre-extraction with alkaline-oxidative post-treatment of corn stover 0:85 Coupling alkaline pre-extraction with alkaline-oxidative post-treatment of corn stover to enhance enzymatic hydrolysis and fermentability. 24693882 15 110 theme Further 2592:2598 arg1 work 2600:2603 Further work 2592:2603 Further work 2592:2603 Further work is required to identify the most economical configuration, including process designs using techno-economic analysis and investigating processing strategies that economize water use. 24693882 4 111 theme g 792:792 arg1 stover 799:804 less than 0.1 g NaOH per g corn stover 767:804 less than 0.1 g NaOH per g corn stover at 80°C 767:812 RESULTS Mild NaOH pre-extraction of corn stover uses less than 0.1 g NaOH per g corn stover at 80°C. 24693882 7 112 theme corn 1202:1205 arg1 stover 1207:1212 corn stover 1202:1212 corn stover 1202:1212 During alkaline pre-extraction, up to 0.10 g of alkali was consumed per g of corn stover. 24693882 5 113 theme cellulolytic 866:877 arg1 enzymes 879:885 cellulolytic enzymes 866:885 cellulolytic enzymes 866:885 The resulting substrates were highly digestible by cellulolytic enzymes at relatively low enzyme loadings and had a strong susceptibility to drying-induced hydrolysis yield losses. 24693882 9 114 theme ELISA 1383:1387 arg1 screening 1389:1397 ELISA screening 1383:1397 ELISA screening of alkali pre-extraction liquors and the AHP post-treatment liquors 1383:1465 ELISA screening of alkali pre-extraction liquors and the AHP post-treatment liquors demonstrated that xyloglucan and β-glucans likely remained tightly bound in the biomass whereas the majority of the soluble polymeric xylans were glucurono (arabino) xylans and potentially homoxylans. 24693882 8 115 theme glucose 1308:1314 arg1 yields 1327:1332 glucose hydrolysis yields 1308:1332 glucose hydrolysis yields 1308:1332 AHP post-treatment at low oxidant loading (25 mg H2O2 per g pre-extracted biomass) increased glucose hydrolysis yields by 5%, which approached near-theoretical yields. 24693882 8 116 dep loading 1249:1255 arg1 H2O2 1264:1267 25 mg H2O2 1258:1267 25 mg H2O2 per g pre-extracted biomass 1258:1295 AHP post-treatment at low oxidant loading (25 mg H2O2 per g pre-extracted biomass) increased glucose hydrolysis yields by 5%, which approached near-theoretical yields. 24693882 3 117 theme extracts 704:711 arg1 pre-extraction 596:609 alkaline pre-extraction 587:609 alkaline pre-extraction 587:609 To better understand the potential of this approach, this study investigates several components of this process including alkaline pre-extraction, alkaline and alkaline-oxidative post-treatment, fermentation, and the composition of alkali extracts. 24693882 3 117 theme extracts 704:711 arg1 composition 682:692 the composition 678:692 the composition of alkali extracts 678:711 To better understand the potential of this approach, this study investigates several components of this process including alkaline pre-extraction, alkaline and alkaline-oxidative post-treatment, fermentation, and the composition of alkali extracts. 24693882 3 117 theme extracts 704:711 arg1 fermentation 660:671 fermentation 660:671 fermentation 660:671 To better understand the potential of this approach, this study investigates several components of this process including alkaline pre-extraction, alkaline and alkaline-oxidative post-treatment, fermentation, and the composition of alkali extracts. 24693882 3 117 theme extracts 704:711 arg1 post-treatment 644:657 alkaline and alkaline-oxidative post-treatment 612:657 post-treatment 644:657 To better understand the potential of this approach, this study investigates several components of this process including alkaline pre-extraction, alkaline and alkaline-oxidative post-treatment, fermentation, and the composition of alkali extracts. 24693882 0 118 theme corn 75:78 arg1 stover 80:85 corn stover 75:85 corn stover 75:85 Coupling alkaline pre-extraction with alkaline-oxidative post-treatment of corn stover to enhance enzymatic hydrolysis and fermentability. 24693882 11 119 theme already-low 1798:1808 arg1 content 1820:1826 the already-low inhibitor content 1794:1826 the already-low inhibitor content 1794:1826 Because the already-low inhibitor content was further decreased in the alkaline pre-extraction, the hydrolysates generated by this two-stage pretreatment were highly fermentable by Saccharomyces cerevisiae strains that were metabolically engineered and evolved for xylose fermentation. 24693882 3 120 theme several 542:548 arg1 components 550:559 several components 542:559 several components of this process 542:575 To better understand the potential of this approach, this study investigates several components of this process including alkaline pre-extraction, alkaline and alkaline-oxidative post-treatment, fermentation, and the composition of alkali extracts. 24693882 9 121 theme pre-extraction 1409:1422 arg1 liquors 1424:1430 alkali pre-extraction liquors 1402:1430 alkali pre-extraction liquors 1402:1430 ELISA screening of alkali pre-extraction liquors and the AHP post-treatment liquors demonstrated that xyloglucan and β-glucans likely remained tightly bound in the biomass whereas the majority of the soluble polymeric xylans were glucurono (arabino) xylans and potentially homoxylans. 24693882 10 122 theme alkaline 1754:1761 arg1 liquor 1778:1783 the alkaline pre-extraction liquor 1750:1783 the alkaline pre-extraction liquor 1750:1783 Pectic polysaccharides were depleted in the AHP post-treatment liquor relative to the alkaline pre-extraction liquor. 24693882 1 123 theme alkaline 264:271 arg1 AHP 292:294 AHP 292:294 AHP 292:294 BACKGROUND A two-stage chemical pretreatment of corn stover is investigated comprising an NaOH pre-extraction followed by an alkaline hydrogen peroxide (AHP) post-treatment. 24693882 1 123 theme alkaline 264:271 arg1 peroxide 282:289 alkaline hydrogen peroxide 264:289 an alkaline hydrogen peroxide (AHP) post-treatment 261:310 BACKGROUND A two-stage chemical pretreatment of corn stover is investigated comprising an NaOH pre-extraction followed by an alkaline hydrogen peroxide (AHP) post-treatment. 24693882 10 124 theme AHP 1712:1714 arg1 liquor 1731:1736 the AHP post-treatment liquor 1708:1736 the AHP post-treatment liquor relative to the alkaline pre-extraction liquor 1708:1783 Pectic polysaccharides were depleted in the AHP post-treatment liquor relative to the alkaline pre-extraction liquor. 24693882 1 125 theme peroxide 282:289 arg1 post-treatment 297:310 an alkaline hydrogen peroxide (AHP) post-treatment 261:310 an alkaline hydrogen peroxide (AHP) post-treatment 261:310 BACKGROUND A two-stage chemical pretreatment of corn stover is investigated comprising an NaOH pre-extraction followed by an alkaline hydrogen peroxide (AHP) post-treatment. 24693882 3 126 theme process 569:575 arg1 components 550:559 several components 542:559 several components of this process 542:575 To better understand the potential of this approach, this study investigates several components of this process including alkaline pre-extraction, alkaline and alkaline-oxidative post-treatment, fermentation, and the composition of alkali extracts. 24693882 9 127 theme AHP 1440:1442 arg1 liquors 1459:1465 the AHP post-treatment liquors 1436:1465 the AHP post-treatment liquors 1436:1465 ELISA screening of alkali pre-extraction liquors and the AHP post-treatment liquors demonstrated that xyloglucan and β-glucans likely remained tightly bound in the biomass whereas the majority of the soluble polymeric xylans were glucurono (arabino) xylans and potentially homoxylans. 24662083 2 0 theme arabinogalactan 357:371 arg1 protein 373:379 an arabinogalactan protein 354:379 an arabinogalactan protein (F2) 354:384 For detailed investigations an arabinogalactan protein (F2) was isolated from seeds and characterized concerning molecular weight, carbohydrate, amino acid composition, linkage, configuration and reaction with β-glucosyl Yariv. 24662083 2 0 theme arabinogalactan 357:371 arg1 F2 382:383 F2 382:383 F2 382:383 For detailed investigations an arabinogalactan protein (F2) was isolated from seeds and characterized concerning molecular weight, carbohydrate, amino acid composition, linkage, configuration and reaction with β-glucosyl Yariv. 24662083 3 1 with assay 710:714 arg1 cells 776:780 human stomach AGS cells 758:780 human stomach AGS cells 758:780 Functional testing of F2 was performed by semiquantitative in situ adhesion assay on sections of human gastric mucosa and by quantitative in vitro adhesion assay with FITC-labled H. pylori strain J99 and human stomach AGS cells. 24662083 3 1 with assay 710:714 arg1 J99 750:752 FITC-labled H. pylori strain J99 721:752 FITC-labled H. pylori strain J99 721:752 Functional testing of F2 was performed by semiquantitative in situ adhesion assay on sections of human gastric mucosa and by quantitative in vitro adhesion assay with FITC-labled H. pylori strain J99 and human stomach AGS cells. 24662083 3 2 dep in 692:693 arg1 vitro 695:699 vitro 695:699 vitro 695:699 Functional testing of F2 was performed by semiquantitative in situ adhesion assay on sections of human gastric mucosa and by quantitative in vitro adhesion assay with FITC-labled H. pylori strain J99 and human stomach AGS cells. 24662083 8 3 theme Radiolabeled 1186:1197 arg1 F2 1199:1200 Radiolabeled F2 1186:1200 Radiolabeled F2 1186:1200 Radiolabeled F2 bound non-specifically to different strains of H. pylori; and to BabA deficient mutant. 24662083 3 4 theme FITC-labled 721:731 arg1 J99 750:752 FITC-labled H. pylori strain J99 721:752 FITC-labled H. pylori strain J99 721:752 Functional testing of F2 was performed by semiquantitative in situ adhesion assay on sections of human gastric mucosa and by quantitative in vitro adhesion assay with FITC-labled H. pylori strain J99 and human stomach AGS cells. 24662083 3 5 theme human 758:762 arg1 cells 776:780 human stomach AGS cells 758:780 human stomach AGS cells 758:780 Functional testing of F2 was performed by semiquantitative in situ adhesion assay on sections of human gastric mucosa and by quantitative in vitro adhesion assay with FITC-labled H. pylori strain J99 and human stomach AGS cells. 24662083 10 6 theme non-specific 1418:1429 arg1 interactions 1431:1442 the non-specific interactions 1414:1442 the non-specific interactions between F2 and the H. pylori 1414:1471 From these data the non-specific interactions between F2 and the H. pylori lead to moderate antiadhesive effects. 24662083 5 7 theme binding 902:908 arg1 studies 910:916 binding studies 902:916 binding studies to H. pylori 902:929 ¹²⁵I-radiolabeled F2 served for binding studies to H. pylori and interaction experiments with BabA and SabA. 24662083 8 8 theme deficient 1272:1280 arg1 mutant 1282:1287 BabA deficient mutant 1267:1287 BabA deficient mutant 1267:1287 Radiolabeled F2 bound non-specifically to different strains of H. pylori; and to BabA deficient mutant. 24662083 3 9 theme F2 576:577 arg1 testing 565:571 Functional testing 554:571 Functional testing of F2 554:577 Functional testing of F2 was performed by semiquantitative in situ adhesion assay on sections of human gastric mucosa and by quantitative in vitro adhesion assay with FITC-labled H. pylori strain J99 and human stomach AGS cells. 24662083 7 10 theme specific 1168:1175 arg1 ligands 1177:1183 its specific ligands 1164:1183 its specific ligands 1164:1183 F2 inhibited the binding of BabA and fibronectin-binding adhesin to its specific ligands. 24662083 2 11 with weight 449:454 arg1 Yariv 547:551 β-glucosyl Yariv 536:551 β-glucosyl Yariv 536:551 For detailed investigations an arabinogalactan protein (F2) was isolated from seeds and characterized concerning molecular weight, carbohydrate, amino acid composition, linkage, configuration and reaction with β-glucosyl Yariv. 24662083 5 12 theme ¹²⁵I-radiolabeled 870:886 arg1 F2 888:889 ¹²⁵I-radiolabeled F2 870:889 ¹²⁵I-radiolabeled F2 870:889 ¹²⁵I-radiolabeled F2 served for binding studies to H. pylori and interaction experiments with BabA and SabA. 24662083 8 13 theme H. 1249:1250 arg1 strains 1238:1244 different strains 1228:1244 different strains of H. pylori 1228:1257 Radiolabeled F2 bound non-specifically to different strains of H. pylori; and to BabA deficient mutant. 24662083 0 14 from seeds 69:73 arg1 properties 13:22 Antiadhesive properties 0:22 Antiadhesive properties of arabinogalactan protein from ribes nigrum seeds against bacterial adhesion of Helicobacter pylori. 0:124 Antiadhesive properties of arabinogalactan protein from ribes nigrum seeds against bacterial adhesion of Helicobacter pylori. 24662083 3 15 theme AGS 772:774 arg1 cells 776:780 human stomach AGS cells 758:780 human stomach AGS cells 758:780 Functional testing of F2 was performed by semiquantitative in situ adhesion assay on sections of human gastric mucosa and by quantitative in vitro adhesion assay with FITC-labled H. pylori strain J99 and human stomach AGS cells. 24662083 3 16 theme semiquantitative 596:611 arg1 assay 630:634 semiquantitative in situ adhesion assay 596:634 semiquantitative in situ adhesion assay on sections of human gastric mucosa 596:670 Functional testing of F2 was performed by semiquantitative in situ adhesion assay on sections of human gastric mucosa and by quantitative in vitro adhesion assay with FITC-labled H. pylori strain J99 and human stomach AGS cells. 24662083 2 17 with carbohydrate 457:468 arg1 Yariv 547:551 β-glucosyl Yariv 536:551 β-glucosyl Yariv 536:551 For detailed investigations an arabinogalactan protein (F2) was isolated from seeds and characterized concerning molecular weight, carbohydrate, amino acid composition, linkage, configuration and reaction with β-glucosyl Yariv. 24662083 5 18 theme interaction 935:945 arg1 experiments 947:957 interaction experiments 935:957 interaction experiments with BabA and SabA 935:976 ¹²⁵I-radiolabeled F2 served for binding studies to H. pylori and interaction experiments with BabA and SabA. 24662083 1 19 theme black 146:150 arg1 Ribes 162:166 Ribes 162:166 Ribes 162:166 Fruit extracts from black currants (Ribes nigrum L.) are traditionally used for treatment of gastritis based on seed polysaccharides that inhibit the adhesion of Helicobacter pylori to stomach cells. 24662083 1 19 theme black 146:150 arg1 currants 152:159 black currants 146:159 black currants (Ribes nigrum L.) 146:177 Fruit extracts from black currants (Ribes nigrum L.) are traditionally used for treatment of gastritis based on seed polysaccharides that inhibit the adhesion of Helicobacter pylori to stomach cells. 24662083 2 20 with composition 482:492 arg1 Yariv 547:551 β-glucosyl Yariv 536:551 β-glucosyl Yariv 536:551 For detailed investigations an arabinogalactan protein (F2) was isolated from seeds and characterized concerning molecular weight, carbohydrate, amino acid composition, linkage, configuration and reaction with β-glucosyl Yariv. 24662083 0 21 theme bacterial 83:91 arg1 adhesion 93:100 bacterial adhesion 83:100 bacterial adhesion of Helicobacter pylori 83:123 Antiadhesive properties of arabinogalactan protein from ribes nigrum seeds against bacterial adhesion of Helicobacter pylori. 24662083 2 22 with linkage 495:501 arg1 Yariv 547:551 β-glucosyl Yariv 536:551 β-glucosyl Yariv 536:551 For detailed investigations an arabinogalactan protein (F2) was isolated from seeds and characterized concerning molecular weight, carbohydrate, amino acid composition, linkage, configuration and reaction with β-glucosyl Yariv. 24662083 2 23 theme β-glucosyl 536:545 arg1 Yariv 547:551 β-glucosyl Yariv 536:551 β-glucosyl Yariv 536:551 For detailed investigations an arabinogalactan protein (F2) was isolated from seeds and characterized concerning molecular weight, carbohydrate, amino acid composition, linkage, configuration and reaction with β-glucosyl Yariv. 24662083 6 24 dep H. 1015:1016 arg1 pylori 1018:1023 H. pylori 1015:1023 H. pylori 1015:1023 F2 had no cytotoxic effects against H. pylori and AGS cells; but inhibited bacterial binding to human gastric cells. 24662083 5 25 with studies 910:916 arg1 SabA 973:976 SabA 973:976 SabA 973:976 ¹²⁵I-radiolabeled F2 served for binding studies to H. pylori and interaction experiments with BabA and SabA. 24662083 5 25 with studies 910:916 arg1 BabA 964:967 BabA 964:967 BabA 964:967 ¹²⁵I-radiolabeled F2 served for binding studies to H. pylori and interaction experiments with BabA and SabA. 24662083 2 26 with configuration 504:516 arg1 Yariv 547:551 β-glucosyl Yariv 536:551 β-glucosyl Yariv 536:551 For detailed investigations an arabinogalactan protein (F2) was isolated from seeds and characterized concerning molecular weight, carbohydrate, amino acid composition, linkage, configuration and reaction with β-glucosyl Yariv. 24662083 5 27 with experiments 947:957 arg1 SabA 973:976 SabA 973:976 SabA 973:976 ¹²⁵I-radiolabeled F2 served for binding studies to H. pylori and interaction experiments with BabA and SabA. 24662083 5 27 with experiments 947:957 arg1 BabA 964:967 BabA 964:967 BabA 964:967 ¹²⁵I-radiolabeled F2 served for binding studies to H. pylori and interaction experiments with BabA and SabA. 24662083 4 28 theme Bacterial 783:791 arg1 adhesins 793:800 Bacterial adhesins 783:800 Bacterial adhesins affected 783:809 Bacterial adhesins affected were identified by overlay assay with immobilized ligands. 24662083 3 29 from assay 630:634 arg1 sections 639:646 sections 639:646 sections of human gastric mucosa 639:670 Functional testing of F2 was performed by semiquantitative in situ adhesion assay on sections of human gastric mucosa and by quantitative in vitro adhesion assay with FITC-labled H. pylori strain J99 and human stomach AGS cells. 24662083 0 30 theme pylori 118:123 arg1 adhesion 93:100 bacterial adhesion 83:100 bacterial adhesion of Helicobacter pylori 83:123 Antiadhesive properties of arabinogalactan protein from ribes nigrum seeds against bacterial adhesion of Helicobacter pylori. 24662083 9 31 theme feedback 1320:1327 arg1 regulation 1329:1338 subsequent feedback regulation 1309:1338 subsequent feedback regulation 1309:1338 F2 did not lead to subsequent feedback regulation or increased expression of adhesins or virulence factors. 24662083 2 32 with reaction 522:529 arg1 Yariv 547:551 β-glucosyl Yariv 536:551 β-glucosyl Yariv 536:551 For detailed investigations an arabinogalactan protein (F2) was isolated from seeds and characterized concerning molecular weight, carbohydrate, amino acid composition, linkage, configuration and reaction with β-glucosyl Yariv. 24662083 6 33 theme gastric 1081:1087 arg1 cells 1089:1093 human gastric cells 1075:1093 human gastric cells 1075:1093 F2 had no cytotoxic effects against H. pylori and AGS cells; but inhibited bacterial binding to human gastric cells. 24662083 1 34 dep Ribes 162:166 arg1 L. 175:176 Ribes nigrum L. 162:176 Ribes nigrum L. 162:176 Fruit extracts from black currants (Ribes nigrum L.) are traditionally used for treatment of gastritis based on seed polysaccharides that inhibit the adhesion of Helicobacter pylori to stomach cells. 24662083 0 35 theme Antiadhesive 0:11 arg1 properties 13:22 Antiadhesive properties 0:22 Antiadhesive properties of arabinogalactan protein from ribes nigrum seeds against bacterial adhesion of Helicobacter pylori. 0:124 Antiadhesive properties of arabinogalactan protein from ribes nigrum seeds against bacterial adhesion of Helicobacter pylori. 24662083 8 36 dep H. 1249:1250 arg1 pylori 1252:1257 H. pylori 1249:1257 H. pylori 1249:1257 Radiolabeled F2 bound non-specifically to different strains of H. pylori; and to BabA deficient mutant. 24662083 1 37 theme Helicobacter 288:299 arg1 pylori 301:306 Helicobacter pylori 288:306 Helicobacter pylori 288:306 Fruit extracts from black currants (Ribes nigrum L.) are traditionally used for treatment of gastritis based on seed polysaccharides that inhibit the adhesion of Helicobacter pylori to stomach cells. 24662083 6 38 theme bacterial 1054:1062 arg1 binding 1064:1070 bacterial binding 1054:1070 bacterial binding to human gastric cells 1054:1093 F2 had no cytotoxic effects against H. pylori and AGS cells; but inhibited bacterial binding to human gastric cells. 24662083 3 39 theme mucosa 665:670 arg1 sections 639:646 sections 639:646 sections of human gastric mucosa 639:670 Functional testing of F2 was performed by semiquantitative in situ adhesion assay on sections of human gastric mucosa and by quantitative in vitro adhesion assay with FITC-labled H. pylori strain J99 and human stomach AGS cells. 24662083 4 40 theme overlay 830:836 arg1 assay 838:842 overlay assay 830:842 overlay assay with immobilized ligands 830:867 Bacterial adhesins affected were identified by overlay assay with immobilized ligands. 24662083 0 41 theme protein 43:49 arg1 properties 13:22 Antiadhesive properties 0:22 Antiadhesive properties of arabinogalactan protein from ribes nigrum seeds against bacterial adhesion of Helicobacter pylori. 0:124 Antiadhesive properties of arabinogalactan protein from ribes nigrum seeds against bacterial adhesion of Helicobacter pylori. 24662083 9 42 theme adhesins 1367:1374 arg1 expression 1353:1362 increased expression 1343:1362 increased expression of adhesins or virulence factors 1343:1395 F2 did not lead to subsequent feedback regulation or increased expression of adhesins or virulence factors. 24662083 9 42 theme adhesins 1367:1374 arg1 regulation 1329:1338 subsequent feedback regulation 1309:1338 subsequent feedback regulation 1309:1338 F2 did not lead to subsequent feedback regulation or increased expression of adhesins or virulence factors. 24662083 2 43 theme amino 471:475 arg1 composition 482:492 amino acid composition 471:492 amino acid composition 471:492 For detailed investigations an arabinogalactan protein (F2) was isolated from seeds and characterized concerning molecular weight, carbohydrate, amino acid composition, linkage, configuration and reaction with β-glucosyl Yariv. 24662083 3 44 theme human 651:655 arg1 mucosa 665:670 human gastric mucosa 651:670 human gastric mucosa 651:670 Functional testing of F2 was performed by semiquantitative in situ adhesion assay on sections of human gastric mucosa and by quantitative in vitro adhesion assay with FITC-labled H. pylori strain J99 and human stomach AGS cells. 24662083 0 45 theme ribes 56:60 arg1 seeds 69:73 ribes nigrum seeds 56:73 ribes nigrum seeds against bacterial adhesion of Helicobacter pylori 56:123 Antiadhesive properties of arabinogalactan protein from ribes nigrum seeds against bacterial adhesion of Helicobacter pylori. 24662083 9 46 theme virulence 1379:1387 arg1 factors 1389:1395 virulence factors 1379:1395 virulence factors 1379:1395 F2 did not lead to subsequent feedback regulation or increased expression of adhesins or virulence factors. 24662083 2 47 attach isolated 390:397 arg2 F2 382:383 F2 382:383 F2 382:383 For detailed investigations an arabinogalactan protein (F2) was isolated from seeds and characterized concerning molecular weight, carbohydrate, amino acid composition, linkage, configuration and reaction with β-glucosyl Yariv. 24662083 2 47 attach isolated 390:397 arg2 protein 373:379 an arabinogalactan protein 354:379 an arabinogalactan protein (F2) 354:384 For detailed investigations an arabinogalactan protein (F2) was isolated from seeds and characterized concerning molecular weight, carbohydrate, amino acid composition, linkage, configuration and reaction with β-glucosyl Yariv. 24662083 2 47 attach isolated 390:397 arg1 seeds 404:408 seeds 404:408 seeds 404:408 For detailed investigations an arabinogalactan protein (F2) was isolated from seeds and characterized concerning molecular weight, carbohydrate, amino acid composition, linkage, configuration and reaction with β-glucosyl Yariv. 24662083 3 48 theme in 692:693 arg1 assay 710:714 quantitative in vitro adhesion assay 679:714 quantitative in vitro adhesion assay with FITC-labled H. pylori strain J99 and human stomach AGS cells 679:780 Functional testing of F2 was performed by semiquantitative in situ adhesion assay on sections of human gastric mucosa and by quantitative in vitro adhesion assay with FITC-labled H. pylori strain J99 and human stomach AGS cells. 24662083 2 49 theme detailed 330:337 arg1 investigations 339:352 detailed investigations 330:352 detailed investigations 330:352 For detailed investigations an arabinogalactan protein (F2) was isolated from seeds and characterized concerning molecular weight, carbohydrate, amino acid composition, linkage, configuration and reaction with β-glucosyl Yariv. 24662083 1 50 theme gastritis 219:227 arg1 treatment 206:214 treatment 206:214 treatment of gastritis based on seed polysaccharides that inhibit the adhesion of Helicobacter pylori to stomach cells 206:323 Fruit extracts from black currants (Ribes nigrum L.) are traditionally used for treatment of gastritis based on seed polysaccharides that inhibit the adhesion of Helicobacter pylori to stomach cells. 24662083 0 51 theme nigrum 62:67 arg1 seeds 69:73 ribes nigrum seeds 56:73 ribes nigrum seeds against bacterial adhesion of Helicobacter pylori 56:123 Antiadhesive properties of arabinogalactan protein from ribes nigrum seeds against bacterial adhesion of Helicobacter pylori. 24662083 1 52 theme stomach 311:317 arg1 cells 319:323 stomach cells 311:323 stomach cells 311:323 Fruit extracts from black currants (Ribes nigrum L.) are traditionally used for treatment of gastritis based on seed polysaccharides that inhibit the adhesion of Helicobacter pylori to stomach cells. 24662083 7 53 theme BabA 1124:1127 arg1 binding 1113:1119 the binding 1109:1119 the binding of BabA and fibronectin-binding adhesin to its specific ligands 1109:1183 F2 inhibited the binding of BabA and fibronectin-binding adhesin to its specific ligands. 24662083 3 54 theme adhesion 701:708 arg1 assay 710:714 quantitative in vitro adhesion assay 679:714 quantitative in vitro adhesion assay with FITC-labled H. pylori strain J99 and human stomach AGS cells 679:780 Functional testing of F2 was performed by semiquantitative in situ adhesion assay on sections of human gastric mucosa and by quantitative in vitro adhesion assay with FITC-labled H. pylori strain J99 and human stomach AGS cells. 24662083 3 55 theme Functional 554:563 arg1 testing 565:571 Functional testing 554:571 Functional testing of F2 554:577 Functional testing of F2 was performed by semiquantitative in situ adhesion assay on sections of human gastric mucosa and by quantitative in vitro adhesion assay with FITC-labled H. pylori strain J99 and human stomach AGS cells. 24662083 3 56 theme strain 743:748 arg1 J99 750:752 FITC-labled H. pylori strain J99 721:752 FITC-labled H. pylori strain J99 721:752 Functional testing of F2 was performed by semiquantitative in situ adhesion assay on sections of human gastric mucosa and by quantitative in vitro adhesion assay with FITC-labled H. pylori strain J99 and human stomach AGS cells. 24662083 7 57 theme adhesin 1153:1159 arg1 binding 1113:1119 the binding 1109:1119 the binding of BabA and fibronectin-binding adhesin to its specific ligands 1109:1183 F2 inhibited the binding of BabA and fibronectin-binding adhesin to its specific ligands. 24662083 4 58 theme immobilized 849:859 arg1 ligands 861:867 immobilized ligands 849:867 immobilized ligands 849:867 Bacterial adhesins affected were identified by overlay assay with immobilized ligands. 24662083 3 59 theme H. 733:734 arg1 J99 750:752 FITC-labled H. pylori strain J99 721:752 FITC-labled H. pylori strain J99 721:752 Functional testing of F2 was performed by semiquantitative in situ adhesion assay on sections of human gastric mucosa and by quantitative in vitro adhesion assay with FITC-labled H. pylori strain J99 and human stomach AGS cells. 24662083 3 60 dep in 613:614 arg1 situ 616:619 situ 616:619 situ 616:619 Functional testing of F2 was performed by semiquantitative in situ adhesion assay on sections of human gastric mucosa and by quantitative in vitro adhesion assay with FITC-labled H. pylori strain J99 and human stomach AGS cells. 24662083 6 61 theme cytotoxic 989:997 arg1 effects 999:1005 no cytotoxic effects 986:1005 no cytotoxic effects 986:1005 F2 had no cytotoxic effects against H. pylori and AGS cells; but inhibited bacterial binding to human gastric cells. 24662083 3 62 theme stomach 764:770 arg1 cells 776:780 human stomach AGS cells 758:780 human stomach AGS cells 758:780 Functional testing of F2 was performed by semiquantitative in situ adhesion assay on sections of human gastric mucosa and by quantitative in vitro adhesion assay with FITC-labled H. pylori strain J99 and human stomach AGS cells. 24662083 8 63 theme BabA 1267:1270 arg1 mutant 1282:1287 BabA deficient mutant 1267:1287 BabA deficient mutant 1267:1287 Radiolabeled F2 bound non-specifically to different strains of H. pylori; and to BabA deficient mutant. 24662083 3 64 theme in 613:614 arg1 assay 630:634 semiquantitative in situ adhesion assay 596:634 semiquantitative in situ adhesion assay on sections of human gastric mucosa 596:670 Functional testing of F2 was performed by semiquantitative in situ adhesion assay on sections of human gastric mucosa and by quantitative in vitro adhesion assay with FITC-labled H. pylori strain J99 and human stomach AGS cells. 24662083 8 65 theme different 1228:1236 arg1 strains 1238:1244 different strains 1228:1244 different strains of H. pylori 1228:1257 Radiolabeled F2 bound non-specifically to different strains of H. pylori; and to BabA deficient mutant. 24662083 1 66 theme Fruit 126:130 arg1 extracts 132:139 Fruit extracts 126:139 Fruit extracts from black currants (Ribes nigrum L.) 126:177 Fruit extracts from black currants (Ribes nigrum L.) are traditionally used for treatment of gastritis based on seed polysaccharides that inhibit the adhesion of Helicobacter pylori to stomach cells. 24662083 1 67 used used 197:200 arg2 extracts 132:139 Fruit extracts 126:139 Fruit extracts from black currants (Ribes nigrum L.) 126:177 Fruit extracts from black currants (Ribes nigrum L.) are traditionally used for treatment of gastritis based on seed polysaccharides that inhibit the adhesion of Helicobacter pylori to stomach cells. 24662083 4 68 with assay 838:842 arg1 ligands 861:867 immobilized ligands 849:867 immobilized ligands 849:867 Bacterial adhesins affected were identified by overlay assay with immobilized ligands. 24662083 3 69 theme adhesion 621:628 arg1 assay 630:634 semiquantitative in situ adhesion assay 596:634 semiquantitative in situ adhesion assay on sections of human gastric mucosa 596:670 Functional testing of F2 was performed by semiquantitative in situ adhesion assay on sections of human gastric mucosa and by quantitative in vitro adhesion assay with FITC-labled H. pylori strain J99 and human stomach AGS cells. 24662083 6 70 theme AGS 1029:1031 arg1 cells 1033:1037 AGS cells 1029:1037 AGS cells 1029:1037 F2 had no cytotoxic effects against H. pylori and AGS cells; but inhibited bacterial binding to human gastric cells. 24662083 5 71 theme H. 921:922 arg1 pylori 924:929 H. pylori 921:929 H. pylori 921:929 ¹²⁵I-radiolabeled F2 served for binding studies to H. pylori and interaction experiments with BabA and SabA. 24662083 0 72 theme Helicobacter 105:116 arg1 pylori 118:123 Helicobacter pylori 105:123 Helicobacter pylori 105:123 Antiadhesive properties of arabinogalactan protein from ribes nigrum seeds against bacterial adhesion of Helicobacter pylori. 24662083 1 73 from currants 152:159 arg1 extracts 132:139 Fruit extracts 126:139 Fruit extracts from black currants (Ribes nigrum L.) 126:177 Fruit extracts from black currants (Ribes nigrum L.) are traditionally used for treatment of gastritis based on seed polysaccharides that inhibit the adhesion of Helicobacter pylori to stomach cells. 24662083 9 74 theme subsequent 1309:1318 arg1 regulation 1329:1338 subsequent feedback regulation 1309:1338 subsequent feedback regulation 1309:1338 F2 did not lead to subsequent feedback regulation or increased expression of adhesins or virulence factors. 24662083 10 75 dep H. 1463:1464 arg1 pylori 1466:1471 the H. pylori 1459:1471 the H. pylori 1459:1471 From these data the non-specific interactions between F2 and the H. pylori lead to moderate antiadhesive effects. 24662083 6 76 theme human 1075:1079 arg1 cells 1089:1093 human gastric cells 1075:1093 human gastric cells 1075:1093 F2 had no cytotoxic effects against H. pylori and AGS cells; but inhibited bacterial binding to human gastric cells. 24662083 10 77 theme moderate 1481:1488 arg1 effects 1503:1509 moderate antiadhesive effects 1481:1509 moderate antiadhesive effects 1481:1509 From these data the non-specific interactions between F2 and the H. pylori lead to moderate antiadhesive effects. 24662083 0 78 theme arabinogalactan 27:41 arg1 protein 43:49 arabinogalactan protein 27:49 arabinogalactan protein 27:49 Antiadhesive properties of arabinogalactan protein from ribes nigrum seeds against bacterial adhesion of Helicobacter pylori. 24662083 9 79 theme increased 1343:1351 arg1 expression 1353:1362 increased expression 1343:1362 increased expression of adhesins or virulence factors 1343:1395 F2 did not lead to subsequent feedback regulation or increased expression of adhesins or virulence factors. 24662083 2 80 theme molecular 439:447 arg1 weight 449:454 molecular weight 439:454 molecular weight 439:454 For detailed investigations an arabinogalactan protein (F2) was isolated from seeds and characterized concerning molecular weight, carbohydrate, amino acid composition, linkage, configuration and reaction with β-glucosyl Yariv. 24662083 3 81 theme gastric 657:663 arg1 mucosa 665:670 human gastric mucosa 651:670 human gastric mucosa 651:670 Functional testing of F2 was performed by semiquantitative in situ adhesion assay on sections of human gastric mucosa and by quantitative in vitro adhesion assay with FITC-labled H. pylori strain J99 and human stomach AGS cells. 24662083 1 82 theme pylori 301:306 arg1 adhesion 276:283 the adhesion 272:283 the adhesion of Helicobacter pylori to stomach cells 272:323 Fruit extracts from black currants (Ribes nigrum L.) are traditionally used for treatment of gastritis based on seed polysaccharides that inhibit the adhesion of Helicobacter pylori to stomach cells. 24662083 2 83 theme acid 477:480 arg1 composition 482:492 amino acid composition 471:492 amino acid composition 471:492 For detailed investigations an arabinogalactan protein (F2) was isolated from seeds and characterized concerning molecular weight, carbohydrate, amino acid composition, linkage, configuration and reaction with β-glucosyl Yariv. 24662083 10 84 theme antiadhesive 1490:1501 arg1 effects 1503:1509 moderate antiadhesive effects 1481:1509 moderate antiadhesive effects 1481:1509 From these data the non-specific interactions between F2 and the H. pylori lead to moderate antiadhesive effects. 24662083 6 85 contain had 982:984 arg2 effects 999:1005 no cytotoxic effects 986:1005 no cytotoxic effects 986:1005 F2 had no cytotoxic effects against H. pylori and AGS cells; but inhibited bacterial binding to human gastric cells. 24662083 6 85 contain had 982:984 arg1 F2 979:980 F2 979:980 F2 979:980 F2 had no cytotoxic effects against H. pylori and AGS cells; but inhibited bacterial binding to human gastric cells. 24662083 7 86 theme fibronectin-binding 1133:1151 arg1 adhesin 1153:1159 fibronectin-binding adhesin 1133:1159 fibronectin-binding adhesin 1133:1159 F2 inhibited the binding of BabA and fibronectin-binding adhesin to its specific ligands. 24662083 3 87 dep H. 733:734 arg1 pylori 736:741 H. pylori 733:741 FITC-labled H. pylori strain J99 721:752 Functional testing of F2 was performed by semiquantitative in situ adhesion assay on sections of human gastric mucosa and by quantitative in vitro adhesion assay with FITC-labled H. pylori strain J99 and human stomach AGS cells. 24662083 3 88 theme quantitative 679:690 arg1 assay 710:714 quantitative in vitro adhesion assay 679:714 quantitative in vitro adhesion assay with FITC-labled H. pylori strain J99 and human stomach AGS cells 679:780 Functional testing of F2 was performed by semiquantitative in situ adhesion assay on sections of human gastric mucosa and by quantitative in vitro adhesion assay with FITC-labled H. pylori strain J99 and human stomach AGS cells. 24662083 9 89 theme factors 1389:1395 arg1 expression 1353:1362 increased expression 1343:1362 increased expression of adhesins or virulence factors 1343:1395 F2 did not lead to subsequent feedback regulation or increased expression of adhesins or virulence factors. 24662083 9 89 theme factors 1389:1395 arg1 regulation 1329:1338 subsequent feedback regulation 1309:1338 subsequent feedback regulation 1309:1338 F2 did not lead to subsequent feedback regulation or increased expression of adhesins or virulence factors. 24662083 1 90 theme seed 238:241 arg1 polysaccharides 243:257 seed polysaccharides 238:257 seed polysaccharides that inhibit the adhesion of Helicobacter pylori to stomach cells 238:323 Fruit extracts from black currants (Ribes nigrum L.) are traditionally used for treatment of gastritis based on seed polysaccharides that inhibit the adhesion of Helicobacter pylori to stomach cells. 26981765 8 0 theme operating 1865:1873 arg1 mode 1875:1878 operating mode 1865:1878 operating mode (with or without permeate flux) 1865:1910 Nonmetric multidimensional scaling of LC-OCD data showed that biofilm samples clustered according to the sampling event (time) regardless of the membrane surface chemistry (hydrophobic or hydrophilic) or operating mode (with or without permeate flux). 26981765 4 1 theme several 834:840 arg1 tools 853:857 several analytical tools 834:857 several analytical tools 834:857 Membrane modules were autopsied after 1, 10, 20 and 30 days of MBR operation, and total extracellular polymeric substances (EPS) accumulated on the membranes were extracted and characterized in detail using several analytical tools, including conventional colorimetric tests (Lowry and Dubois), liquid chromatography with organic carbon detection (LC-OCD), fluorescence excitation - emission matrices (FEEM), fourier transform infrared (FTIR) and confocal laser scanning microscope (CLSM). 26981765 4 2 theme emission 1010:1017 arg1 FEEM 1029:1032 FEEM 1029:1032 FEEM 1029:1032 Membrane modules were autopsied after 1, 10, 20 and 30 days of MBR operation, and total extracellular polymeric substances (EPS) accumulated on the membranes were extracted and characterized in detail using several analytical tools, including conventional colorimetric tests (Lowry and Dubois), liquid chromatography with organic carbon detection (LC-OCD), fluorescence excitation - emission matrices (FEEM), fourier transform infrared (FTIR) and confocal laser scanning microscope (CLSM). 26981765 4 2 theme emission 1010:1017 arg1 matrices 1019:1026 emission matrices 1010:1026 emission matrices (FEEM) 1010:1033 Membrane modules were autopsied after 1, 10, 20 and 30 days of MBR operation, and total extracellular polymeric substances (EPS) accumulated on the membranes were extracted and characterized in detail using several analytical tools, including conventional colorimetric tests (Lowry and Dubois), liquid chromatography with organic carbon detection (LC-OCD), fluorescence excitation - emission matrices (FEEM), fourier transform infrared (FTIR) and confocal laser scanning microscope (CLSM). 26981765 9 3 theme biofouling 2203:2212 arg1 impact 2193:2198 impact 2193:2198 impact 2193:2198 These results suggest that EPS composition may not be the dominant parameter for evaluating membrane performance and possibly other parameters such as biofilm thickness, porosity, compactness and structure should be considered in future studies for evaluating the development and impact of biofouling on membrane performance. 26981765 9 3 theme biofouling 2203:2212 arg1 development 2177:2187 development 2177:2187 development 2177:2187 These results suggest that EPS composition may not be the dominant parameter for evaluating membrane performance and possibly other parameters such as biofilm thickness, porosity, compactness and structure should be considered in future studies for evaluating the development and impact of biofouling on membrane performance. 26981765 8 4 theme membrane 1806:1813 arg1 chemistry 1823:1831 the membrane surface chemistry 1802:1831 the membrane surface chemistry (hydrophobic or hydrophilic) 1802:1860 Nonmetric multidimensional scaling of LC-OCD data showed that biofilm samples clustered according to the sampling event (time) regardless of the membrane surface chemistry (hydrophobic or hydrophilic) or operating mode (with or without permeate flux). 26981765 6 5 theme foulants 1369:1376 arg1 foulants 1369:1376 foulants 1369:1376 foulants 1369:1376 The sulfonated polysulfone (SPSU) membrane had the highest negatively charged membrane surface, accumulated the least amount of foulants and displayed the lowest TMP. 26981765 6 5 theme foulants 1369:1376 arg1 amount 1359:1364 the least amount 1349:1364 the least amount of foulants 1349:1376 The sulfonated polysulfone (SPSU) membrane had the highest negatively charged membrane surface, accumulated the least amount of foulants and displayed the lowest TMP. 26981765 3 6 dep  h 582:583 arg1 2 580:580 2 580:580 2 580:580 In addition, identical membrane modules without permeate production (0 L/m(2) h) were operated in the same lab-scale MBR. 26981765 6 7 contain had 1284:1286 arg2 surface 1328:1334 the highest negatively charged membrane surface 1288:1334 the highest negatively charged membrane surface 1288:1334 The sulfonated polysulfone (SPSU) membrane had the highest negatively charged membrane surface, accumulated the least amount of foulants and displayed the lowest TMP. 26981765 6 7 contain had 1284:1286 arg1 membrane 1275:1282 The sulfonated polysulfone (SPSU) membrane 1241:1282 The sulfonated polysulfone (SPSU) membrane 1241:1282 The sulfonated polysulfone (SPSU) membrane had the highest negatively charged membrane surface, accumulated the least amount of foulants and displayed the lowest TMP. 26981765 7 8 theme filtration 1569:1578 arg1 stages 1559:1564 early stages 1553:1564 early stages of filtration (day 1) 1553:1586 The same type of organic foulants developed with time on the four membranes and the composition of biopolymers shifted from protein dominance at early stages of filtration (day 1) towards polysaccharides dominance during later stages of MBR filtration. 26981765 4 9 theme colorimetric 883:894 arg1 Dubois 913:918 Dubois 913:918 Dubois 913:918 Membrane modules were autopsied after 1, 10, 20 and 30 days of MBR operation, and total extracellular polymeric substances (EPS) accumulated on the membranes were extracted and characterized in detail using several analytical tools, including conventional colorimetric tests (Lowry and Dubois), liquid chromatography with organic carbon detection (LC-OCD), fluorescence excitation - emission matrices (FEEM), fourier transform infrared (FTIR) and confocal laser scanning microscope (CLSM). 26981765 4 9 theme colorimetric 883:894 arg1 Lowry 903:907 Lowry 903:907 Lowry 903:907 Membrane modules were autopsied after 1, 10, 20 and 30 days of MBR operation, and total extracellular polymeric substances (EPS) accumulated on the membranes were extracted and characterized in detail using several analytical tools, including conventional colorimetric tests (Lowry and Dubois), liquid chromatography with organic carbon detection (LC-OCD), fluorescence excitation - emission matrices (FEEM), fourier transform infrared (FTIR) and confocal laser scanning microscope (CLSM). 26981765 4 9 theme colorimetric 883:894 arg1 tests 896:900 conventional colorimetric tests 870:900 conventional colorimetric tests (Lowry and Dubois) 870:919 Membrane modules were autopsied after 1, 10, 20 and 30 days of MBR operation, and total extracellular polymeric substances (EPS) accumulated on the membranes were extracted and characterized in detail using several analytical tools, including conventional colorimetric tests (Lowry and Dubois), liquid chromatography with organic carbon detection (LC-OCD), fluorescence excitation - emission matrices (FEEM), fourier transform infrared (FTIR) and confocal laser scanning microscope (CLSM). 26981765 6 10 theme SPSU 1269:1272 arg1 membrane 1275:1282 The sulfonated polysulfone (SPSU) membrane 1241:1282 The sulfonated polysulfone (SPSU) membrane 1241:1282 The sulfonated polysulfone (SPSU) membrane had the highest negatively charged membrane surface, accumulated the least amount of foulants and displayed the lowest TMP. 26981765 3 11 theme 0 L/m 574:578 arg1 production 562:571 permeate production 553:571 permeate production (0 L/m(2) h) 553:584 In addition, identical membrane modules without permeate production (0 L/m(2) h) were operated in the same lab-scale MBR. 26981765 3 11 theme 0 L/m 574:578 arg1  h 582:583 0 L/m(2) h 574:583 0 L/m(2) h 574:583 In addition, identical membrane modules without permeate production (0 L/m(2) h) were operated in the same lab-scale MBR. 26981765 8 12 theme multidimensional 1671:1686 arg1 scaling 1688:1694 Nonmetric multidimensional scaling 1661:1694 Nonmetric multidimensional scaling of LC-OCD data 1661:1709 Nonmetric multidimensional scaling of LC-OCD data showed that biofilm samples clustered according to the sampling event (time) regardless of the membrane surface chemistry (hydrophobic or hydrophilic) or operating mode (with or without permeate flux). 26981765 4 13 theme Membrane 627:634 arg1 modules 636:642 Membrane modules 627:642 Membrane modules 627:642 Membrane modules were autopsied after 1, 10, 20 and 30 days of MBR operation, and total extracellular polymeric substances (EPS) accumulated on the membranes were extracted and characterized in detail using several analytical tools, including conventional colorimetric tests (Lowry and Dubois), liquid chromatography with organic carbon detection (LC-OCD), fluorescence excitation - emission matrices (FEEM), fourier transform infrared (FTIR) and confocal laser scanning microscope (CLSM). 26981765 6 14 theme polysulfone 1256:1266 arg1 membrane 1275:1282 The sulfonated polysulfone (SPSU) membrane 1241:1282 The sulfonated polysulfone (SPSU) membrane 1241:1282 The sulfonated polysulfone (SPSU) membrane had the highest negatively charged membrane surface, accumulated the least amount of foulants and displayed the lowest TMP. 26981765 1 15 from biofouling 223:232 arg1 MBRs 259:262 MBRs 259:262 MBRs 259:262 Membrane surface hydrophilic modification has always been considered to mitigating biofouling in membrane bioreactors (MBRs). 26981765 1 15 from biofouling 223:232 arg1 bioreactors 246:256 membrane bioreactors 237:256 membrane bioreactors (MBRs) 237:263 Membrane surface hydrophilic modification has always been considered to mitigating biofouling in membrane bioreactors (MBRs). 26981765 7 16 theme protein 1532:1538 arg1 dominance 1540:1548 protein dominance 1532:1548 protein dominance at early stages of filtration (day 1) 1532:1586 The same type of organic foulants developed with time on the four membranes and the composition of biopolymers shifted from protein dominance at early stages of filtration (day 1) towards polysaccharides dominance during later stages of MBR filtration. 26981765 3 17 theme same 607:610 arg1 MBR 622:624 the same lab-scale MBR 603:624 the same lab-scale MBR 603:624 In addition, identical membrane modules without permeate production (0 L/m(2) h) were operated in the same lab-scale MBR. 26981765 3 18 dep production 562:571 arg1 permeate 553:560 permeate 553:560 permeate 553:560 In addition, identical membrane modules without permeate production (0 L/m(2) h) were operated in the same lab-scale MBR. 26981765 7 19 theme filtration 1649:1658 arg1 stages 1635:1640 later stages 1629:1640 later stages of MBR filtration 1629:1658 The same type of organic foulants developed with time on the four membranes and the composition of biopolymers shifted from protein dominance at early stages of filtration (day 1) towards polysaccharides dominance during later stages of MBR filtration. 26981765 4 20 theme liquid 922:927 arg1 chromatography 929:942 liquid chromatography 922:942 liquid chromatography with organic carbon detection (LC-OCD) 922:981 Membrane modules were autopsied after 1, 10, 20 and 30 days of MBR operation, and total extracellular polymeric substances (EPS) accumulated on the membranes were extracted and characterized in detail using several analytical tools, including conventional colorimetric tests (Lowry and Dubois), liquid chromatography with organic carbon detection (LC-OCD), fluorescence excitation - emission matrices (FEEM), fourier transform infrared (FTIR) and confocal laser scanning microscope (CLSM). 26981765 4 21 theme laser 1083:1087 arg1 microscope 1098:1107 confocal laser scanning microscope 1074:1107 confocal laser scanning microscope (CLSM) 1074:1114 Membrane modules were autopsied after 1, 10, 20 and 30 days of MBR operation, and total extracellular polymeric substances (EPS) accumulated on the membranes were extracted and characterized in detail using several analytical tools, including conventional colorimetric tests (Lowry and Dubois), liquid chromatography with organic carbon detection (LC-OCD), fluorescence excitation - emission matrices (FEEM), fourier transform infrared (FTIR) and confocal laser scanning microscope (CLSM). 26981765 4 21 theme laser 1083:1087 arg1 CLSM 1110:1113 CLSM 1110:1113 CLSM 1110:1113 Membrane modules were autopsied after 1, 10, 20 and 30 days of MBR operation, and total extracellular polymeric substances (EPS) accumulated on the membranes were extracted and characterized in detail using several analytical tools, including conventional colorimetric tests (Lowry and Dubois), liquid chromatography with organic carbon detection (LC-OCD), fluorescence excitation - emission matrices (FEEM), fourier transform infrared (FTIR) and confocal laser scanning microscope (CLSM). 26981765 5 22 theme hydrophilic 1223:1233 arg1 ones 1235:1238 hydrophilic ones 1223:1238 hydrophilic ones 1223:1238 The transmembrane pressure (TMP) quickly stabilized with higher values for the hydrophobic membranes than hydrophilic ones. 26981765 6 23 theme membrane 1319:1326 arg1 surface 1328:1334 the highest negatively charged membrane surface 1288:1334 the highest negatively charged membrane surface 1288:1334 The sulfonated polysulfone (SPSU) membrane had the highest negatively charged membrane surface, accumulated the least amount of foulants and displayed the lowest TMP. 26981765 0 24 theme membrane 86:93 arg1 surfaces 95:102 hydrophobic and hydrophilic membrane surfaces 58:102 hydrophobic and hydrophilic membrane surfaces 58:102 Temporal changes in extracellular polymeric substances on hydrophobic and hydrophilic membrane surfaces in a submerged membrane bioreactor. 26981765 7 25 theme later 1629:1633 arg1 stages 1635:1640 later stages 1629:1640 later stages of MBR filtration 1629:1658 The same type of organic foulants developed with time on the four membranes and the composition of biopolymers shifted from protein dominance at early stages of filtration (day 1) towards polysaccharides dominance during later stages of MBR filtration. 26981765 2 26 theme ultrafiltration 284:298 arg1 sizes 316:320 pore sizes ∼0.1 μm 311:328 pore sizes ∼0.1 μm 311:328 Four hollow-fiber ultrafiltration membranes (pore sizes ∼0.1 μm) differing only in hydrophobic or hydrophilic surface characteristics were operated at a permeate flux of 10 L/m(2) h in the same lab-scale MBR fed with synthetic wastewater. 26981765 2 26 theme ultrafiltration 284:298 arg1 membranes 300:308 Four hollow-fiber ultrafiltration membranes 266:308 Four hollow-fiber ultrafiltration membranes (pore sizes ∼0.1 μm) differing only in hydrophobic or hydrophilic surface characteristics 266:398 Four hollow-fiber ultrafiltration membranes (pore sizes ∼0.1 μm) differing only in hydrophobic or hydrophilic surface characteristics were operated at a permeate flux of 10 L/m(2) h in the same lab-scale MBR fed with synthetic wastewater. 26981765 4 27 theme total 709:713 arg1 EPS 751:753 EPS 751:753 EPS 751:753 Membrane modules were autopsied after 1, 10, 20 and 30 days of MBR operation, and total extracellular polymeric substances (EPS) accumulated on the membranes were extracted and characterized in detail using several analytical tools, including conventional colorimetric tests (Lowry and Dubois), liquid chromatography with organic carbon detection (LC-OCD), fluorescence excitation - emission matrices (FEEM), fourier transform infrared (FTIR) and confocal laser scanning microscope (CLSM). 26981765 4 27 theme total 709:713 arg1 substances 739:748 total extracellular polymeric substances 709:748 total extracellular polymeric substances (EPS) 709:754 Membrane modules were autopsied after 1, 10, 20 and 30 days of MBR operation, and total extracellular polymeric substances (EPS) accumulated on the membranes were extracted and characterized in detail using several analytical tools, including conventional colorimetric tests (Lowry and Dubois), liquid chromatography with organic carbon detection (LC-OCD), fluorescence excitation - emission matrices (FEEM), fourier transform infrared (FTIR) and confocal laser scanning microscope (CLSM). 26981765 1 28 theme surface 149:155 arg1 modification 169:180 Membrane surface hydrophilic modification 140:180 Membrane surface hydrophilic modification 140:180 Membrane surface hydrophilic modification has always been considered to mitigating biofouling in membrane bioreactors (MBRs). 26981765 9 29 theme EPS 1940:1942 arg1 parameter 1980:1988 the dominant parameter 1967:1988 the dominant parameter for evaluating membrane performance 1967:2024 These results suggest that EPS composition may not be the dominant parameter for evaluating membrane performance and possibly other parameters such as biofilm thickness, porosity, compactness and structure should be considered in future studies for evaluating the development and impact of biofouling on membrane performance. 26981765 9 29 theme EPS 1940:1942 arg1 composition 1944:1954 EPS composition 1940:1954 EPS composition 1940:1954 These results suggest that EPS composition may not be the dominant parameter for evaluating membrane performance and possibly other parameters such as biofilm thickness, porosity, compactness and structure should be considered in future studies for evaluating the development and impact of biofouling on membrane performance. 26981765 4 30 theme polymeric 729:737 arg1 EPS 751:753 EPS 751:753 EPS 751:753 Membrane modules were autopsied after 1, 10, 20 and 30 days of MBR operation, and total extracellular polymeric substances (EPS) accumulated on the membranes were extracted and characterized in detail using several analytical tools, including conventional colorimetric tests (Lowry and Dubois), liquid chromatography with organic carbon detection (LC-OCD), fluorescence excitation - emission matrices (FEEM), fourier transform infrared (FTIR) and confocal laser scanning microscope (CLSM). 26981765 4 30 theme polymeric 729:737 arg1 substances 739:748 total extracellular polymeric substances 709:748 total extracellular polymeric substances (EPS) 709:754 Membrane modules were autopsied after 1, 10, 20 and 30 days of MBR operation, and total extracellular polymeric substances (EPS) accumulated on the membranes were extracted and characterized in detail using several analytical tools, including conventional colorimetric tests (Lowry and Dubois), liquid chromatography with organic carbon detection (LC-OCD), fluorescence excitation - emission matrices (FEEM), fourier transform infrared (FTIR) and confocal laser scanning microscope (CLSM). 26981765 0 31 theme submerged 109:117 arg1 bioreactor 128:137 a submerged membrane bioreactor 107:137 a submerged membrane bioreactor 107:137 Temporal changes in extracellular polymeric substances on hydrophobic and hydrophilic membrane surfaces in a submerged membrane bioreactor. 26981765 2 32 dep  h 445:446 arg1 2 443:443 2 443:443 2 443:443 Four hollow-fiber ultrafiltration membranes (pore sizes ∼0.1 μm) differing only in hydrophobic or hydrophilic surface characteristics were operated at a permeate flux of 10 L/m(2) h in the same lab-scale MBR fed with synthetic wastewater. 26981765 8 33 theme event 1775:1779 arg1 time 1782:1785 the sampling event (time) 1762:1786 the sampling event (time) regardless of the membrane surface chemistry (hydrophobic or hydrophilic) or operating mode (with or without permeate flux) 1762:1910 Nonmetric multidimensional scaling of LC-OCD data showed that biofilm samples clustered according to the sampling event (time) regardless of the membrane surface chemistry (hydrophobic or hydrophilic) or operating mode (with or without permeate flux). 26981765 2 34 theme same 455:458 arg1 MBR 470:472 the same lab-scale MBR 451:472 the same lab-scale MBR fed with synthetic wastewater 451:502 Four hollow-fiber ultrafiltration membranes (pore sizes ∼0.1 μm) differing only in hydrophobic or hydrophilic surface characteristics were operated at a permeate flux of 10 L/m(2) h in the same lab-scale MBR fed with synthetic wastewater. 26981765 4 35 theme MBR 690:692 arg1 operation 694:702 MBR operation 690:702 MBR operation 690:702 Membrane modules were autopsied after 1, 10, 20 and 30 days of MBR operation, and total extracellular polymeric substances (EPS) accumulated on the membranes were extracted and characterized in detail using several analytical tools, including conventional colorimetric tests (Lowry and Dubois), liquid chromatography with organic carbon detection (LC-OCD), fluorescence excitation - emission matrices (FEEM), fourier transform infrared (FTIR) and confocal laser scanning microscope (CLSM). 26981765 2 36 theme permeate 419:426 arg1 flux 428:431 a permeate flux 417:431 a permeate flux of 10 L/m(2) h in the same lab-scale MBR fed with synthetic wastewater 417:502 Four hollow-fiber ultrafiltration membranes (pore sizes ∼0.1 μm) differing only in hydrophobic or hydrophilic surface characteristics were operated at a permeate flux of 10 L/m(2) h in the same lab-scale MBR fed with synthetic wastewater. 26981765 0 37 theme Temporal 0:7 arg1 changes 9:15 Temporal changes 0:15 Temporal changes in extracellular polymeric substances on hydrophobic and hydrophilic membrane surfaces in a submerged membrane bioreactor. 0:138 Temporal changes in extracellular polymeric substances on hydrophobic and hydrophilic membrane surfaces in a submerged membrane bioreactor. 26981765 4 38 theme fluorescence 984:995 arg1 excitation 997:1006 fluorescence excitation 984:1006 fluorescence excitation 984:1006 Membrane modules were autopsied after 1, 10, 20 and 30 days of MBR operation, and total extracellular polymeric substances (EPS) accumulated on the membranes were extracted and characterized in detail using several analytical tools, including conventional colorimetric tests (Lowry and Dubois), liquid chromatography with organic carbon detection (LC-OCD), fluorescence excitation - emission matrices (FEEM), fourier transform infrared (FTIR) and confocal laser scanning microscope (CLSM). 26981765 9 39 theme membrane 2217:2224 arg1 performance 2226:2236 membrane performance 2217:2236 membrane performance 2217:2236 These results suggest that EPS composition may not be the dominant parameter for evaluating membrane performance and possibly other parameters such as biofilm thickness, porosity, compactness and structure should be considered in future studies for evaluating the development and impact of biofouling on membrane performance. 26981765 4 40 theme carbon 957:962 arg1 detection 964:972 organic carbon detection 949:972 organic carbon detection (LC-OCD) 949:981 Membrane modules were autopsied after 1, 10, 20 and 30 days of MBR operation, and total extracellular polymeric substances (EPS) accumulated on the membranes were extracted and characterized in detail using several analytical tools, including conventional colorimetric tests (Lowry and Dubois), liquid chromatography with organic carbon detection (LC-OCD), fluorescence excitation - emission matrices (FEEM), fourier transform infrared (FTIR) and confocal laser scanning microscope (CLSM). 26981765 4 40 theme carbon 957:962 arg1 LC-OCD 975:980 LC-OCD 975:980 LC-OCD 975:980 Membrane modules were autopsied after 1, 10, 20 and 30 days of MBR operation, and total extracellular polymeric substances (EPS) accumulated on the membranes were extracted and characterized in detail using several analytical tools, including conventional colorimetric tests (Lowry and Dubois), liquid chromatography with organic carbon detection (LC-OCD), fluorescence excitation - emission matrices (FEEM), fourier transform infrared (FTIR) and confocal laser scanning microscope (CLSM). 26981765 9 41 theme dominant 1971:1978 arg1 parameter 1980:1988 the dominant parameter 1967:1988 the dominant parameter for evaluating membrane performance 1967:2024 These results suggest that EPS composition may not be the dominant parameter for evaluating membrane performance and possibly other parameters such as biofilm thickness, porosity, compactness and structure should be considered in future studies for evaluating the development and impact of biofouling on membrane performance. 26981765 9 41 theme dominant 1971:1978 arg1 composition 1944:1954 EPS composition 1940:1954 EPS composition 1940:1954 These results suggest that EPS composition may not be the dominant parameter for evaluating membrane performance and possibly other parameters such as biofilm thickness, porosity, compactness and structure should be considered in future studies for evaluating the development and impact of biofouling on membrane performance. 26981765 0 42 theme polymeric 34:42 arg1 substances 44:53 extracellular polymeric substances 20:53 extracellular polymeric substances 20:53 Temporal changes in extracellular polymeric substances on hydrophobic and hydrophilic membrane surfaces in a submerged membrane bioreactor. 26981765 4 43 dep using 828:832 arg1 including 860:868 including 860:868 including conventional colorimetric tests (Lowry and Dubois), liquid chromatography with organic carbon detection (LC-OCD), fluorescence excitation - emission matrices (FEEM) 860:1033 Membrane modules were autopsied after 1, 10, 20 and 30 days of MBR operation, and total extracellular polymeric substances (EPS) accumulated on the membranes were extracted and characterized in detail using several analytical tools, including conventional colorimetric tests (Lowry and Dubois), liquid chromatography with organic carbon detection (LC-OCD), fluorescence excitation - emission matrices (FEEM), fourier transform infrared (FTIR) and confocal laser scanning microscope (CLSM). 26981765 2 44 theme surface 376:382 arg1 characteristics 384:398 hydrophobic or hydrophilic surface characteristics 349:398 hydrophobic or hydrophilic surface characteristics 349:398 Four hollow-fiber ultrafiltration membranes (pore sizes ∼0.1 μm) differing only in hydrophobic or hydrophilic surface characteristics were operated at a permeate flux of 10 L/m(2) h in the same lab-scale MBR fed with synthetic wastewater. 26981765 7 45 theme foulants 1433:1440 arg1 type 1417:1420 The same type 1408:1420 The same type of organic foulants 1408:1440 The same type of organic foulants developed with time on the four membranes and the composition of biopolymers shifted from protein dominance at early stages of filtration (day 1) towards polysaccharides dominance during later stages of MBR filtration. 26981765 9 46 theme membrane 2005:2012 arg1 performance 2014:2024 membrane performance 2005:2024 membrane performance 2005:2024 These results suggest that EPS composition may not be the dominant parameter for evaluating membrane performance and possibly other parameters such as biofilm thickness, porosity, compactness and structure should be considered in future studies for evaluating the development and impact of biofouling on membrane performance. 26981765 3 47 theme identical 518:526 arg1 modules 537:543 identical membrane modules 518:543 identical membrane modules without permeate production (0 L/m(2) h) 518:584 In addition, identical membrane modules without permeate production (0 L/m(2) h) were operated in the same lab-scale MBR. 26981765 7 48 theme same 1412:1415 arg1 type 1417:1420 The same type 1408:1420 The same type of organic foulants 1408:1440 The same type of organic foulants developed with time on the four membranes and the composition of biopolymers shifted from protein dominance at early stages of filtration (day 1) towards polysaccharides dominance during later stages of MBR filtration. 26981765 9 49 theme other 2039:2043 arg1 parameters 2045:2054 possibly other parameters 2030:2054 possibly other parameters such as biofilm thickness, porosity, compactness and structure 2030:2117 These results suggest that EPS composition may not be the dominant parameter for evaluating membrane performance and possibly other parameters such as biofilm thickness, porosity, compactness and structure should be considered in future studies for evaluating the development and impact of biofouling on membrane performance. 26981765 9 49 theme other 2039:2043 arg1 compactness 2093:2103 compactness 2093:2103 compactness 2093:2103 These results suggest that EPS composition may not be the dominant parameter for evaluating membrane performance and possibly other parameters such as biofilm thickness, porosity, compactness and structure should be considered in future studies for evaluating the development and impact of biofouling on membrane performance. 26981765 9 49 theme other 2039:2043 arg1 porosity 2083:2090 porosity 2083:2090 porosity 2083:2090 These results suggest that EPS composition may not be the dominant parameter for evaluating membrane performance and possibly other parameters such as biofilm thickness, porosity, compactness and structure should be considered in future studies for evaluating the development and impact of biofouling on membrane performance. 26981765 9 49 theme other 2039:2043 arg1 thickness 2072:2080 biofilm thickness 2064:2080 biofilm thickness 2064:2080 These results suggest that EPS composition may not be the dominant parameter for evaluating membrane performance and possibly other parameters such as biofilm thickness, porosity, compactness and structure should be considered in future studies for evaluating the development and impact of biofouling on membrane performance. 26981765 9 49 theme other 2039:2043 arg1 structure 2109:2117 structure 2109:2117 structure 2109:2117 These results suggest that EPS composition may not be the dominant parameter for evaluating membrane performance and possibly other parameters such as biofilm thickness, porosity, compactness and structure should be considered in future studies for evaluating the development and impact of biofouling on membrane performance. 26981765 6 50 theme lowest 1396:1401 arg1 TMP 1403:1405 the lowest TMP 1392:1405 the lowest TMP 1392:1405 The sulfonated polysulfone (SPSU) membrane had the highest negatively charged membrane surface, accumulated the least amount of foulants and displayed the lowest TMP. 26981765 5 51 theme transmembrane 1121:1133 arg1 TMP 1145:1147 TMP 1145:1147 TMP 1145:1147 The transmembrane pressure (TMP) quickly stabilized with higher values for the hydrophobic membranes than hydrophilic ones. 26981765 5 51 theme transmembrane 1121:1133 arg1 pressure 1135:1142 The transmembrane pressure 1117:1142 The transmembrane pressure (TMP) 1117:1148 The transmembrane pressure (TMP) quickly stabilized with higher values for the hydrophobic membranes than hydrophilic ones. 26981765 7 52 from time 1457:1460 arg1 membranes 1474:1482 the four membranes 1465:1482 the four membranes 1465:1482 The same type of organic foulants developed with time on the four membranes and the composition of biopolymers shifted from protein dominance at early stages of filtration (day 1) towards polysaccharides dominance during later stages of MBR filtration. 26981765 7 52 from time 1457:1460 arg1 composition 1492:1502 the composition 1488:1502 the composition of biopolymers shifted from protein dominance at early stages of filtration (day 1) towards polysaccharides dominance during later stages of MBR filtration 1488:1658 The same type of organic foulants developed with time on the four membranes and the composition of biopolymers shifted from protein dominance at early stages of filtration (day 1) towards polysaccharides dominance during later stages of MBR filtration. 26981765 8 53 dep flux 1906:1909 arg1 permeate 1897:1904 permeate 1897:1904 permeate 1897:1904 Nonmetric multidimensional scaling of LC-OCD data showed that biofilm samples clustered according to the sampling event (time) regardless of the membrane surface chemistry (hydrophobic or hydrophilic) or operating mode (with or without permeate flux). 26981765 8 54 theme data 1706:1709 arg1 scaling 1688:1694 Nonmetric multidimensional scaling 1661:1694 Nonmetric multidimensional scaling of LC-OCD data 1661:1709 Nonmetric multidimensional scaling of LC-OCD data showed that biofilm samples clustered according to the sampling event (time) regardless of the membrane surface chemistry (hydrophobic or hydrophilic) or operating mode (with or without permeate flux). 26981765 9 55 theme biofilm 2064:2070 arg1 thickness 2072:2080 biofilm thickness 2064:2080 biofilm thickness 2064:2080 These results suggest that EPS composition may not be the dominant parameter for evaluating membrane performance and possibly other parameters such as biofilm thickness, porosity, compactness and structure should be considered in future studies for evaluating the development and impact of biofouling on membrane performance. 26981765 8 56 theme surface 1815:1821 arg1 chemistry 1823:1831 the membrane surface chemistry 1802:1831 the membrane surface chemistry (hydrophobic or hydrophilic) 1802:1860 Nonmetric multidimensional scaling of LC-OCD data showed that biofilm samples clustered according to the sampling event (time) regardless of the membrane surface chemistry (hydrophobic or hydrophilic) or operating mode (with or without permeate flux). 26981765 2 57 theme pore 311:314 arg1 sizes 316:320 pore sizes ∼0.1 μm 311:328 pore sizes ∼0.1 μm 311:328 Four hollow-fiber ultrafiltration membranes (pore sizes ∼0.1 μm) differing only in hydrophobic or hydrophilic surface characteristics were operated at a permeate flux of 10 L/m(2) h in the same lab-scale MBR fed with synthetic wastewater. 26981765 2 57 theme pore 311:314 arg1 membranes 300:308 Four hollow-fiber ultrafiltration membranes 266:308 Four hollow-fiber ultrafiltration membranes (pore sizes ∼0.1 μm) differing only in hydrophobic or hydrophilic surface characteristics 266:398 Four hollow-fiber ultrafiltration membranes (pore sizes ∼0.1 μm) differing only in hydrophobic or hydrophilic surface characteristics were operated at a permeate flux of 10 L/m(2) h in the same lab-scale MBR fed with synthetic wastewater. 26981765 4 58 theme confocal 1074:1081 arg1 microscope 1098:1107 confocal laser scanning microscope 1074:1107 confocal laser scanning microscope (CLSM) 1074:1114 Membrane modules were autopsied after 1, 10, 20 and 30 days of MBR operation, and total extracellular polymeric substances (EPS) accumulated on the membranes were extracted and characterized in detail using several analytical tools, including conventional colorimetric tests (Lowry and Dubois), liquid chromatography with organic carbon detection (LC-OCD), fluorescence excitation - emission matrices (FEEM), fourier transform infrared (FTIR) and confocal laser scanning microscope (CLSM). 26981765 4 58 theme confocal 1074:1081 arg1 CLSM 1110:1113 CLSM 1110:1113 CLSM 1110:1113 Membrane modules were autopsied after 1, 10, 20 and 30 days of MBR operation, and total extracellular polymeric substances (EPS) accumulated on the membranes were extracted and characterized in detail using several analytical tools, including conventional colorimetric tests (Lowry and Dubois), liquid chromatography with organic carbon detection (LC-OCD), fluorescence excitation - emission matrices (FEEM), fourier transform infrared (FTIR) and confocal laser scanning microscope (CLSM). 26981765 9 59 dep development 2177:2187 arg1 the 2173:2175 the 2173:2175 the 2173:2175 These results suggest that EPS composition may not be the dominant parameter for evaluating membrane performance and possibly other parameters such as biofilm thickness, porosity, compactness and structure should be considered in future studies for evaluating the development and impact of biofouling on membrane performance. 26981765 7 60 theme early 1553:1557 arg1 stages 1559:1564 early stages 1553:1564 early stages of filtration (day 1) 1553:1586 The same type of organic foulants developed with time on the four membranes and the composition of biopolymers shifted from protein dominance at early stages of filtration (day 1) towards polysaccharides dominance during later stages of MBR filtration. 26981765 4 61 theme conventional 870:881 arg1 Dubois 913:918 Dubois 913:918 Dubois 913:918 Membrane modules were autopsied after 1, 10, 20 and 30 days of MBR operation, and total extracellular polymeric substances (EPS) accumulated on the membranes were extracted and characterized in detail using several analytical tools, including conventional colorimetric tests (Lowry and Dubois), liquid chromatography with organic carbon detection (LC-OCD), fluorescence excitation - emission matrices (FEEM), fourier transform infrared (FTIR) and confocal laser scanning microscope (CLSM). 26981765 4 61 theme conventional 870:881 arg1 Lowry 903:907 Lowry 903:907 Lowry 903:907 Membrane modules were autopsied after 1, 10, 20 and 30 days of MBR operation, and total extracellular polymeric substances (EPS) accumulated on the membranes were extracted and characterized in detail using several analytical tools, including conventional colorimetric tests (Lowry and Dubois), liquid chromatography with organic carbon detection (LC-OCD), fluorescence excitation - emission matrices (FEEM), fourier transform infrared (FTIR) and confocal laser scanning microscope (CLSM). 26981765 4 61 theme conventional 870:881 arg1 tests 896:900 conventional colorimetric tests 870:900 conventional colorimetric tests (Lowry and Dubois) 870:919 Membrane modules were autopsied after 1, 10, 20 and 30 days of MBR operation, and total extracellular polymeric substances (EPS) accumulated on the membranes were extracted and characterized in detail using several analytical tools, including conventional colorimetric tests (Lowry and Dubois), liquid chromatography with organic carbon detection (LC-OCD), fluorescence excitation - emission matrices (FEEM), fourier transform infrared (FTIR) and confocal laser scanning microscope (CLSM). 26981765 8 62 theme Nonmetric 1661:1669 arg1 scaling 1688:1694 Nonmetric multidimensional scaling 1661:1694 Nonmetric multidimensional scaling of LC-OCD data 1661:1709 Nonmetric multidimensional scaling of LC-OCD data showed that biofilm samples clustered according to the sampling event (time) regardless of the membrane surface chemistry (hydrophobic or hydrophilic) or operating mode (with or without permeate flux). 26981765 1 63 theme membrane 237:244 arg1 MBRs 259:262 MBRs 259:262 MBRs 259:262 Membrane surface hydrophilic modification has always been considered to mitigating biofouling in membrane bioreactors (MBRs). 26981765 1 63 theme membrane 237:244 arg1 bioreactors 246:256 membrane bioreactors 237:256 membrane bioreactors (MBRs) 237:263 Membrane surface hydrophilic modification has always been considered to mitigating biofouling in membrane bioreactors (MBRs). 26981765 6 64 theme sulfonated 1245:1254 arg1 membrane 1275:1282 The sulfonated polysulfone (SPSU) membrane 1241:1282 The sulfonated polysulfone (SPSU) membrane 1241:1282 The sulfonated polysulfone (SPSU) membrane had the highest negatively charged membrane surface, accumulated the least amount of foulants and displayed the lowest TMP. 26981765 4 65 dep infrared 1054:1061 arg1 FTIR 1064:1067 FTIR 1064:1067 FTIR 1064:1067 Membrane modules were autopsied after 1, 10, 20 and 30 days of MBR operation, and total extracellular polymeric substances (EPS) accumulated on the membranes were extracted and characterized in detail using several analytical tools, including conventional colorimetric tests (Lowry and Dubois), liquid chromatography with organic carbon detection (LC-OCD), fluorescence excitation - emission matrices (FEEM), fourier transform infrared (FTIR) and confocal laser scanning microscope (CLSM). 26981765 4 66 theme analytical 842:851 arg1 tools 853:857 several analytical tools 834:857 several analytical tools 834:857 Membrane modules were autopsied after 1, 10, 20 and 30 days of MBR operation, and total extracellular polymeric substances (EPS) accumulated on the membranes were extracted and characterized in detail using several analytical tools, including conventional colorimetric tests (Lowry and Dubois), liquid chromatography with organic carbon detection (LC-OCD), fluorescence excitation - emission matrices (FEEM), fourier transform infrared (FTIR) and confocal laser scanning microscope (CLSM). 26981765 5 67 theme hydrophobic 1196:1206 arg1 membranes 1208:1216 the hydrophobic membranes 1192:1216 the hydrophobic membranes than hydrophilic ones 1192:1238 The transmembrane pressure (TMP) quickly stabilized with higher values for the hydrophobic membranes than hydrophilic ones. 26981765 8 68 theme LC-OCD 1699:1704 arg1 data 1706:1709 LC-OCD data 1699:1709 LC-OCD data 1699:1709 Nonmetric multidimensional scaling of LC-OCD data showed that biofilm samples clustered according to the sampling event (time) regardless of the membrane surface chemistry (hydrophobic or hydrophilic) or operating mode (with or without permeate flux). 26981765 1 69 theme Membrane 140:147 arg1 modification 169:180 Membrane surface hydrophilic modification 140:180 Membrane surface hydrophilic modification 140:180 Membrane surface hydrophilic modification has always been considered to mitigating biofouling in membrane bioreactors (MBRs). 26981765 7 70 theme biopolymers 1507:1517 arg1 membranes 1474:1482 the four membranes 1465:1482 the four membranes 1465:1482 The same type of organic foulants developed with time on the four membranes and the composition of biopolymers shifted from protein dominance at early stages of filtration (day 1) towards polysaccharides dominance during later stages of MBR filtration. 26981765 7 70 theme biopolymers 1507:1517 arg1 composition 1492:1502 the composition 1488:1502 the composition of biopolymers shifted from protein dominance at early stages of filtration (day 1) towards polysaccharides dominance during later stages of MBR filtration 1488:1658 The same type of organic foulants developed with time on the four membranes and the composition of biopolymers shifted from protein dominance at early stages of filtration (day 1) towards polysaccharides dominance during later stages of MBR filtration. 26981765 4 71 theme scanning 1089:1096 arg1 microscope 1098:1107 confocal laser scanning microscope 1074:1107 confocal laser scanning microscope (CLSM) 1074:1114 Membrane modules were autopsied after 1, 10, 20 and 30 days of MBR operation, and total extracellular polymeric substances (EPS) accumulated on the membranes were extracted and characterized in detail using several analytical tools, including conventional colorimetric tests (Lowry and Dubois), liquid chromatography with organic carbon detection (LC-OCD), fluorescence excitation - emission matrices (FEEM), fourier transform infrared (FTIR) and confocal laser scanning microscope (CLSM). 26981765 4 71 theme scanning 1089:1096 arg1 CLSM 1110:1113 CLSM 1110:1113 CLSM 1110:1113 Membrane modules were autopsied after 1, 10, 20 and 30 days of MBR operation, and total extracellular polymeric substances (EPS) accumulated on the membranes were extracted and characterized in detail using several analytical tools, including conventional colorimetric tests (Lowry and Dubois), liquid chromatography with organic carbon detection (LC-OCD), fluorescence excitation - emission matrices (FEEM), fourier transform infrared (FTIR) and confocal laser scanning microscope (CLSM). 26981765 9 72 theme future 2143:2148 arg1 studies 2150:2156 future studies 2143:2156 future studies for evaluating the development and impact of biofouling on membrane performance 2143:2236 These results suggest that EPS composition may not be the dominant parameter for evaluating membrane performance and possibly other parameters such as biofilm thickness, porosity, compactness and structure should be considered in future studies for evaluating the development and impact of biofouling on membrane performance. 26981765 0 73 theme hydrophilic 74:84 arg1 surfaces 95:102 hydrophobic and hydrophilic membrane surfaces 58:102 hydrophobic and hydrophilic membrane surfaces 58:102 Temporal changes in extracellular polymeric substances on hydrophobic and hydrophilic membrane surfaces in a submerged membrane bioreactor. 26981765 2 74 theme hollow-fiber 271:282 arg1 sizes 316:320 pore sizes ∼0.1 μm 311:328 pore sizes ∼0.1 μm 311:328 Four hollow-fiber ultrafiltration membranes (pore sizes ∼0.1 μm) differing only in hydrophobic or hydrophilic surface characteristics were operated at a permeate flux of 10 L/m(2) h in the same lab-scale MBR fed with synthetic wastewater. 26981765 2 74 theme hollow-fiber 271:282 arg1 membranes 300:308 Four hollow-fiber ultrafiltration membranes 266:308 Four hollow-fiber ultrafiltration membranes (pore sizes ∼0.1 μm) differing only in hydrophobic or hydrophilic surface characteristics 266:398 Four hollow-fiber ultrafiltration membranes (pore sizes ∼0.1 μm) differing only in hydrophobic or hydrophilic surface characteristics were operated at a permeate flux of 10 L/m(2) h in the same lab-scale MBR fed with synthetic wastewater. 26981765 1 75 theme hydrophilic 157:167 arg1 modification 169:180 Membrane surface hydrophilic modification 140:180 Membrane surface hydrophilic modification 140:180 Membrane surface hydrophilic modification has always been considered to mitigating biofouling in membrane bioreactors (MBRs). 26981765 8 76 dep chemistry 1823:1831 arg1 hydrophilic 1849:1859 hydrophilic 1849:1859 hydrophilic 1849:1859 Nonmetric multidimensional scaling of LC-OCD data showed that biofilm samples clustered according to the sampling event (time) regardless of the membrane surface chemistry (hydrophobic or hydrophilic) or operating mode (with or without permeate flux). 26981765 8 76 dep chemistry 1823:1831 arg1 hydrophobic 1834:1844 hydrophobic 1834:1844 hydrophobic 1834:1844 Nonmetric multidimensional scaling of LC-OCD data showed that biofilm samples clustered according to the sampling event (time) regardless of the membrane surface chemistry (hydrophobic or hydrophilic) or operating mode (with or without permeate flux). 26981765 5 77 theme higher 1174:1179 arg1 values 1181:1186 higher values 1174:1186 higher values for the hydrophobic membranes than hydrophilic ones 1174:1238 The transmembrane pressure (TMP) quickly stabilized with higher values for the hydrophobic membranes than hydrophilic ones. 26981765 6 78 theme charged 1311:1317 arg1 surface 1328:1334 the highest negatively charged membrane surface 1288:1334 the highest negatively charged membrane surface 1288:1334 The sulfonated polysulfone (SPSU) membrane had the highest negatively charged membrane surface, accumulated the least amount of foulants and displayed the lowest TMP. 26981765 8 79 theme biofilm 1723:1729 arg1 samples 1731:1737 biofilm samples 1723:1737 biofilm samples 1723:1737 Nonmetric multidimensional scaling of LC-OCD data showed that biofilm samples clustered according to the sampling event (time) regardless of the membrane surface chemistry (hydrophobic or hydrophilic) or operating mode (with or without permeate flux). 26981765 7 80 theme MBR 1645:1647 arg1 filtration 1649:1658 MBR filtration 1645:1658 MBR filtration 1645:1658 The same type of organic foulants developed with time on the four membranes and the composition of biopolymers shifted from protein dominance at early stages of filtration (day 1) towards polysaccharides dominance during later stages of MBR filtration. 26981765 2 81 theme synthetic 483:491 arg1 wastewater 493:502 synthetic wastewater 483:502 synthetic wastewater 483:502 Four hollow-fiber ultrafiltration membranes (pore sizes ∼0.1 μm) differing only in hydrophobic or hydrophilic surface characteristics were operated at a permeate flux of 10 L/m(2) h in the same lab-scale MBR fed with synthetic wastewater. 26981765 0 82 from changes 9:15 arg1 substances 44:53 extracellular polymeric substances 20:53 extracellular polymeric substances 20:53 Temporal changes in extracellular polymeric substances on hydrophobic and hydrophilic membrane surfaces in a submerged membrane bioreactor. 26981765 0 82 from changes 9:15 arg1 bioreactor 128:137 a submerged membrane bioreactor 107:137 a submerged membrane bioreactor 107:137 Temporal changes in extracellular polymeric substances on hydrophobic and hydrophilic membrane surfaces in a submerged membrane bioreactor. 26981765 0 82 from changes 9:15 arg1 surfaces 95:102 hydrophobic and hydrophilic membrane surfaces 58:102 hydrophobic and hydrophilic membrane surfaces 58:102 Temporal changes in extracellular polymeric substances on hydrophobic and hydrophilic membrane surfaces in a submerged membrane bioreactor. 26981765 6 83 theme highest 1292:1298 arg1 surface 1328:1334 the highest negatively charged membrane surface 1288:1334 the highest negatively charged membrane surface 1288:1334 The sulfonated polysulfone (SPSU) membrane had the highest negatively charged membrane surface, accumulated the least amount of foulants and displayed the lowest TMP. 26981765 0 84 theme membrane 119:126 arg1 bioreactor 128:137 a submerged membrane bioreactor 107:137 a submerged membrane bioreactor 107:137 Temporal changes in extracellular polymeric substances on hydrophobic and hydrophilic membrane surfaces in a submerged membrane bioreactor. 26981765 4 85 theme extracellular 715:727 arg1 EPS 751:753 EPS 751:753 EPS 751:753 Membrane modules were autopsied after 1, 10, 20 and 30 days of MBR operation, and total extracellular polymeric substances (EPS) accumulated on the membranes were extracted and characterized in detail using several analytical tools, including conventional colorimetric tests (Lowry and Dubois), liquid chromatography with organic carbon detection (LC-OCD), fluorescence excitation - emission matrices (FEEM), fourier transform infrared (FTIR) and confocal laser scanning microscope (CLSM). 26981765 4 85 theme extracellular 715:727 arg1 substances 739:748 total extracellular polymeric substances 709:748 total extracellular polymeric substances (EPS) 709:754 Membrane modules were autopsied after 1, 10, 20 and 30 days of MBR operation, and total extracellular polymeric substances (EPS) accumulated on the membranes were extracted and characterized in detail using several analytical tools, including conventional colorimetric tests (Lowry and Dubois), liquid chromatography with organic carbon detection (LC-OCD), fluorescence excitation - emission matrices (FEEM), fourier transform infrared (FTIR) and confocal laser scanning microscope (CLSM). 26981765 8 86 theme sampling 1766:1773 arg1 time 1782:1785 the sampling event (time) 1762:1786 the sampling event (time) regardless of the membrane surface chemistry (hydrophobic or hydrophilic) or operating mode (with or without permeate flux) 1762:1910 Nonmetric multidimensional scaling of LC-OCD data showed that biofilm samples clustered according to the sampling event (time) regardless of the membrane surface chemistry (hydrophobic or hydrophilic) or operating mode (with or without permeate flux). 26981765 7 87 theme polysaccharides 1596:1610 arg1 dominance 1612:1620 polysaccharides dominance 1596:1620 polysaccharides dominance during later stages of MBR filtration 1596:1658 The same type of organic foulants developed with time on the four membranes and the composition of biopolymers shifted from protein dominance at early stages of filtration (day 1) towards polysaccharides dominance during later stages of MBR filtration. 26981765 0 88 theme extracellular 20:32 arg1 substances 44:53 extracellular polymeric substances 20:53 extracellular polymeric substances 20:53 Temporal changes in extracellular polymeric substances on hydrophobic and hydrophilic membrane surfaces in a submerged membrane bioreactor. 26981765 2 89 theme  h 445:446 arg1 flux 428:431 a permeate flux 417:431 a permeate flux of 10 L/m(2) h in the same lab-scale MBR fed with synthetic wastewater 417:502 Four hollow-fiber ultrafiltration membranes (pore sizes ∼0.1 μm) differing only in hydrophobic or hydrophilic surface characteristics were operated at a permeate flux of 10 L/m(2) h in the same lab-scale MBR fed with synthetic wastewater. 26981765 4 90 theme operation 694:702 arg1 days 682:685 1, 10, 20 and 30 days 665:685 1, 10, 20 and 30 days of MBR operation 665:702 Membrane modules were autopsied after 1, 10, 20 and 30 days of MBR operation, and total extracellular polymeric substances (EPS) accumulated on the membranes were extracted and characterized in detail using several analytical tools, including conventional colorimetric tests (Lowry and Dubois), liquid chromatography with organic carbon detection (LC-OCD), fluorescence excitation - emission matrices (FEEM), fourier transform infrared (FTIR) and confocal laser scanning microscope (CLSM). 26981765 6 91 theme least 1353:1357 arg1 foulants 1369:1376 foulants 1369:1376 foulants 1369:1376 The sulfonated polysulfone (SPSU) membrane had the highest negatively charged membrane surface, accumulated the least amount of foulants and displayed the lowest TMP. 26981765 6 91 theme least 1353:1357 arg1 amount 1359:1364 the least amount 1349:1364 the least amount of foulants 1349:1376 The sulfonated polysulfone (SPSU) membrane had the highest negatively charged membrane surface, accumulated the least amount of foulants and displayed the lowest TMP. 26981765 4 92 theme organic 949:955 arg1 detection 964:972 organic carbon detection 949:972 organic carbon detection (LC-OCD) 949:981 Membrane modules were autopsied after 1, 10, 20 and 30 days of MBR operation, and total extracellular polymeric substances (EPS) accumulated on the membranes were extracted and characterized in detail using several analytical tools, including conventional colorimetric tests (Lowry and Dubois), liquid chromatography with organic carbon detection (LC-OCD), fluorescence excitation - emission matrices (FEEM), fourier transform infrared (FTIR) and confocal laser scanning microscope (CLSM). 26981765 4 92 theme organic 949:955 arg1 LC-OCD 975:980 LC-OCD 975:980 LC-OCD 975:980 Membrane modules were autopsied after 1, 10, 20 and 30 days of MBR operation, and total extracellular polymeric substances (EPS) accumulated on the membranes were extracted and characterized in detail using several analytical tools, including conventional colorimetric tests (Lowry and Dubois), liquid chromatography with organic carbon detection (LC-OCD), fluorescence excitation - emission matrices (FEEM), fourier transform infrared (FTIR) and confocal laser scanning microscope (CLSM). 26981765 3 93 theme lab-scale 612:620 arg1 MBR 622:624 the same lab-scale MBR 603:624 the same lab-scale MBR 603:624 In addition, identical membrane modules without permeate production (0 L/m(2) h) were operated in the same lab-scale MBR. 26981765 2 94 theme 10 L/m 436:441 arg1  h 445:446 10 L/m(2) h 436:446 10 L/m(2) h 436:446 Four hollow-fiber ultrafiltration membranes (pore sizes ∼0.1 μm) differing only in hydrophobic or hydrophilic surface characteristics were operated at a permeate flux of 10 L/m(2) h in the same lab-scale MBR fed with synthetic wastewater. 26981765 0 95 theme hydrophobic 58:68 arg1 surfaces 95:102 hydrophobic and hydrophilic membrane surfaces 58:102 hydrophobic and hydrophilic membrane surfaces 58:102 Temporal changes in extracellular polymeric substances on hydrophobic and hydrophilic membrane surfaces in a submerged membrane bioreactor. 26981765 4 96 with chromatography 929:942 arg1 detection 964:972 organic carbon detection 949:972 organic carbon detection (LC-OCD) 949:981 Membrane modules were autopsied after 1, 10, 20 and 30 days of MBR operation, and total extracellular polymeric substances (EPS) accumulated on the membranes were extracted and characterized in detail using several analytical tools, including conventional colorimetric tests (Lowry and Dubois), liquid chromatography with organic carbon detection (LC-OCD), fluorescence excitation - emission matrices (FEEM), fourier transform infrared (FTIR) and confocal laser scanning microscope (CLSM). 26981765 4 96 with chromatography 929:942 arg1 LC-OCD 975:980 LC-OCD 975:980 LC-OCD 975:980 Membrane modules were autopsied after 1, 10, 20 and 30 days of MBR operation, and total extracellular polymeric substances (EPS) accumulated on the membranes were extracted and characterized in detail using several analytical tools, including conventional colorimetric tests (Lowry and Dubois), liquid chromatography with organic carbon detection (LC-OCD), fluorescence excitation - emission matrices (FEEM), fourier transform infrared (FTIR) and confocal laser scanning microscope (CLSM). 26981765 2 97 theme lab-scale 460:468 arg1 MBR 470:472 the same lab-scale MBR 451:472 the same lab-scale MBR fed with synthetic wastewater 451:502 Four hollow-fiber ultrafiltration membranes (pore sizes ∼0.1 μm) differing only in hydrophobic or hydrophilic surface characteristics were operated at a permeate flux of 10 L/m(2) h in the same lab-scale MBR fed with synthetic wastewater. 26981765 7 98 from stages 1559:1564 arg1 dominance 1540:1548 protein dominance 1532:1548 protein dominance at early stages of filtration (day 1) 1532:1586 The same type of organic foulants developed with time on the four membranes and the composition of biopolymers shifted from protein dominance at early stages of filtration (day 1) towards polysaccharides dominance during later stages of MBR filtration. 26981765 2 99 theme hydrophilic 364:374 arg1 characteristics 384:398 hydrophobic or hydrophilic surface characteristics 349:398 hydrophobic or hydrophilic surface characteristics 349:398 Four hollow-fiber ultrafiltration membranes (pore sizes ∼0.1 μm) differing only in hydrophobic or hydrophilic surface characteristics were operated at a permeate flux of 10 L/m(2) h in the same lab-scale MBR fed with synthetic wastewater. 26981765 2 100 from flux 428:431 arg1 MBR 470:472 the same lab-scale MBR 451:472 the same lab-scale MBR fed with synthetic wastewater 451:502 Four hollow-fiber ultrafiltration membranes (pore sizes ∼0.1 μm) differing only in hydrophobic or hydrophilic surface characteristics were operated at a permeate flux of 10 L/m(2) h in the same lab-scale MBR fed with synthetic wastewater. 26981765 2 101 theme hydrophobic 349:359 arg1 characteristics 384:398 hydrophobic or hydrophilic surface characteristics 349:398 hydrophobic or hydrophilic surface characteristics 349:398 Four hollow-fiber ultrafiltration membranes (pore sizes ∼0.1 μm) differing only in hydrophobic or hydrophilic surface characteristics were operated at a permeate flux of 10 L/m(2) h in the same lab-scale MBR fed with synthetic wastewater. 26981765 7 102 theme organic 1425:1431 arg1 foulants 1433:1440 organic foulants 1425:1440 organic foulants 1425:1440 The same type of organic foulants developed with time on the four membranes and the composition of biopolymers shifted from protein dominance at early stages of filtration (day 1) towards polysaccharides dominance during later stages of MBR filtration. 26981765 3 103 theme membrane 528:535 arg1 modules 537:543 identical membrane modules 518:543 identical membrane modules without permeate production (0 L/m(2) h) 518:584 In addition, identical membrane modules without permeate production (0 L/m(2) h) were operated in the same lab-scale MBR. 27375256 7 0 theme wine 1267:1270 arg1 properties 1289:1298 very complex properties 1276:1298 very complex properties influenced by other wine compounds and their interactions, as well as probably by the specific chemical composition of a given wine 1276:1430 Wine quality improvement did not correlate with the polysaccharide, protein, mannan, or aromatic compound concentrations, suggesting that the mouthfeel and foaming quality of sparkling wine are very complex properties influenced by other wine compounds and their interactions, as well as probably by the specific chemical composition of a given wine. 27375256 7 0 theme wine 1267:1270 arg1 quality 1246:1252 the mouthfeel and foaming quality 1220:1252 the mouthfeel and foaming quality of sparkling wine 1220:1270 Wine quality improvement did not correlate with the polysaccharide, protein, mannan, or aromatic compound concentrations, suggesting that the mouthfeel and foaming quality of sparkling wine are very complex properties influenced by other wine compounds and their interactions, as well as probably by the specific chemical composition of a given wine. 27375256 1 1 from process 180:186 arg1 presence 195:202 the presence 191:202 the presence of dead yeast cells 191:222 The quality of traditional sparkling-wine depends on the aging process in the presence of dead yeast cells. 27375256 4 2 theme making 729:734 arg1 sparkling-wine 714:727 sparkling-wine making 714:734 sparkling-wine making 714:734 These yeasts killed sensitive strains in killer plate assays done under conditions of low pH and temperature similar to those used in sparkling-wine making, although some strains showed a different killer behaviour during the second fermentation. 27375256 7 3 theme chemical 1395:1402 arg1 composition 1404:1414 the specific chemical composition 1382:1414 the specific chemical composition of a given wine 1382:1430 Wine quality improvement did not correlate with the polysaccharide, protein, mannan, or aromatic compound concentrations, suggesting that the mouthfeel and foaming quality of sparkling wine are very complex properties influenced by other wine compounds and their interactions, as well as probably by the specific chemical composition of a given wine. 27375256 7 4 theme aromatic 1170:1177 arg1 concentrations 1188:1201 aromatic compound concentrations 1170:1201 aromatic compound concentrations 1170:1201 Wine quality improvement did not correlate with the polysaccharide, protein, mannan, or aromatic compound concentrations, suggesting that the mouthfeel and foaming quality of sparkling wine are very complex properties influenced by other wine compounds and their interactions, as well as probably by the specific chemical composition of a given wine. 27375256 5 5 theme slow 931:934 arg1 killer 936:941 slow killer 931:941 the slow killer effect 927:948 The fast killer effect improved the foam quality and mouthfeel of the mixed-inoculated wines, while the slow killer effect gave small improvements over single-inoculated wines. 27375256 0 6 theme traditional 89:99 arg1 sparkling-wine 101:114 traditional sparkling-wine 89:114 traditional sparkling-wine 89:114 Using mixed inocula of Saccharomyces cerevisiae killer strains to improve the quality of traditional sparkling-wine. 27375256 4 7 theme similar 689:695 arg1 pH 670:671 low pH 666:671 low pH 666:671 These yeasts killed sensitive strains in killer plate assays done under conditions of low pH and temperature similar to those used in sparkling-wine making, although some strains showed a different killer behaviour during the second fermentation. 27375256 4 8 theme plate 628:632 arg1 assays 634:639 killer plate assays 621:639 killer plate assays done under conditions of low pH and temperature similar to those used in sparkling-wine making 621:734 These yeasts killed sensitive strains in killer plate assays done under conditions of low pH and temperature similar to those used in sparkling-wine making, although some strains showed a different killer behaviour during the second fermentation. 27375256 7 9 theme sparkling 1257:1265 arg1 wine 1267:1270 sparkling wine 1257:1270 sparkling wine 1257:1270 Wine quality improvement did not correlate with the polysaccharide, protein, mannan, or aromatic compound concentrations, suggesting that the mouthfeel and foaming quality of sparkling wine are very complex properties influenced by other wine compounds and their interactions, as well as probably by the specific chemical composition of a given wine. 27375256 3 10 dep cell 494:497 arg1 death 499:503 death 499:503 death 499:503 Saccharomyces cerevisiae killer yeasts were tested to increase cell death and autolysis during mixed-yeast-inoculated second fermentation and aging. 27375256 4 11 theme killer 621:626 arg1 assays 634:639 killer plate assays 621:639 killer plate assays done under conditions of low pH and temperature similar to those used in sparkling-wine making 621:734 These yeasts killed sensitive strains in killer plate assays done under conditions of low pH and temperature similar to those used in sparkling-wine making, although some strains showed a different killer behaviour during the second fermentation. 27375256 7 12 theme foaming 1238:1244 arg1 properties 1289:1298 very complex properties 1276:1298 very complex properties influenced by other wine compounds and their interactions, as well as probably by the specific chemical composition of a given wine 1276:1430 Wine quality improvement did not correlate with the polysaccharide, protein, mannan, or aromatic compound concentrations, suggesting that the mouthfeel and foaming quality of sparkling wine are very complex properties influenced by other wine compounds and their interactions, as well as probably by the specific chemical composition of a given wine. 27375256 7 12 theme foaming 1238:1244 arg1 quality 1246:1252 the mouthfeel and foaming quality 1220:1252 the mouthfeel and foaming quality of sparkling wine 1220:1270 Wine quality improvement did not correlate with the polysaccharide, protein, mannan, or aromatic compound concentrations, suggesting that the mouthfeel and foaming quality of sparkling wine are very complex properties influenced by other wine compounds and their interactions, as well as probably by the specific chemical composition of a given wine. 27375256 5 13 theme killer 836:841 arg1 effect 843:848 The fast killer effect 827:848 The fast killer effect 827:848 The fast killer effect improved the foam quality and mouthfeel of the mixed-inoculated wines, while the slow killer effect gave small improvements over single-inoculated wines. 27375256 4 14 theme second 806:811 arg1 fermentation 813:824 the second fermentation 802:824 the second fermentation 802:824 These yeasts killed sensitive strains in killer plate assays done under conditions of low pH and temperature similar to those used in sparkling-wine making, although some strains showed a different killer behaviour during the second fermentation. 27375256 1 15 theme aging 174:178 arg1 process 180:186 the aging process 170:186 the aging process in the presence of dead yeast cells 170:222 The quality of traditional sparkling-wine depends on the aging process in the presence of dead yeast cells. 27375256 0 16 theme sparkling-wine 101:114 arg1 quality 78:84 the quality 74:84 the quality of traditional sparkling-wine 74:114 Using mixed inocula of Saccharomyces cerevisiae killer strains to improve the quality of traditional sparkling-wine. 27375256 3 17 theme killer 456:461 arg1 yeasts 463:468 Saccharomyces cerevisiae killer yeasts 431:468 Saccharomyces cerevisiae killer yeasts 431:468 Saccharomyces cerevisiae killer yeasts were tested to increase cell death and autolysis during mixed-yeast-inoculated second fermentation and aging. 27375256 0 18 theme mixed 6:10 arg1 inocula 12:18 mixed inocula 6:18 mixed inocula of Saccharomyces cerevisiae killer strains 6:61 Using mixed inocula of Saccharomyces cerevisiae killer strains to improve the quality of traditional sparkling-wine. 27375256 2 19 theme colloidal 311:319 arg1 mannoproteins 358:370 mannoproteins 358:370 mannoproteins 358:370 These cells undergo a slow autolysis process thereby releasing some compounds, mostly colloidal polymers such as polysaccharides and mannoproteins, which influence the wine's foam properties and mouthfeel. 27375256 2 19 theme colloidal 311:319 arg1 polymers 321:328 mostly colloidal polymers 304:328 mostly colloidal polymers such as polysaccharides and mannoproteins, which influence the wine's foam properties and mouthfeel 304:428 These cells undergo a slow autolysis process thereby releasing some compounds, mostly colloidal polymers such as polysaccharides and mannoproteins, which influence the wine's foam properties and mouthfeel. 27375256 2 19 theme colloidal 311:319 arg1 polysaccharides 338:352 polysaccharides 338:352 polysaccharides 338:352 These cells undergo a slow autolysis process thereby releasing some compounds, mostly colloidal polymers such as polysaccharides and mannoproteins, which influence the wine's foam properties and mouthfeel. 27375256 2 19 theme colloidal 311:319 arg1 compounds 293:301 some compounds 288:301 some compounds 288:301 These cells undergo a slow autolysis process thereby releasing some compounds, mostly colloidal polymers such as polysaccharides and mannoproteins, which influence the wine's foam properties and mouthfeel. 27375256 7 20 theme mouthfeel 1224:1232 arg1 properties 1289:1298 very complex properties 1276:1298 very complex properties influenced by other wine compounds and their interactions, as well as probably by the specific chemical composition of a given wine 1276:1430 Wine quality improvement did not correlate with the polysaccharide, protein, mannan, or aromatic compound concentrations, suggesting that the mouthfeel and foaming quality of sparkling wine are very complex properties influenced by other wine compounds and their interactions, as well as probably by the specific chemical composition of a given wine. 27375256 7 20 theme mouthfeel 1224:1232 arg1 quality 1246:1252 the mouthfeel and foaming quality 1220:1252 the mouthfeel and foaming quality of sparkling wine 1220:1270 Wine quality improvement did not correlate with the polysaccharide, protein, mannan, or aromatic compound concentrations, suggesting that the mouthfeel and foaming quality of sparkling wine are very complex properties influenced by other wine compounds and their interactions, as well as probably by the specific chemical composition of a given wine. 27375256 5 21 theme mixed-inoculated 897:912 arg1 wines 914:918 the mixed-inoculated wines 893:918 the mixed-inoculated wines 893:918 The fast killer effect improved the foam quality and mouthfeel of the mixed-inoculated wines, while the slow killer effect gave small improvements over single-inoculated wines. 27375256 5 22 theme wines 914:918 arg1 mouthfeel 880:888 mouthfeel 880:888 mouthfeel 880:888 The fast killer effect improved the foam quality and mouthfeel of the mixed-inoculated wines, while the slow killer effect gave small improvements over single-inoculated wines. 27375256 5 22 theme wines 914:918 arg1 quality 868:874 foam quality 863:874 foam quality 863:874 The fast killer effect improved the foam quality and mouthfeel of the mixed-inoculated wines, while the slow killer effect gave small improvements over single-inoculated wines. 27375256 5 23 theme small 955:959 arg1 improvements 961:972 small improvements 955:972 small improvements 955:972 The fast killer effect improved the foam quality and mouthfeel of the mixed-inoculated wines, while the slow killer effect gave small improvements over single-inoculated wines. 27375256 4 24 theme killer 778:783 arg1 behaviour 785:793 a different killer behaviour 766:793 a different killer behaviour 766:793 These yeasts killed sensitive strains in killer plate assays done under conditions of low pH and temperature similar to those used in sparkling-wine making, although some strains showed a different killer behaviour during the second fermentation. 27375256 7 25 theme wine 1427:1430 arg1 composition 1404:1414 the specific chemical composition 1382:1414 the specific chemical composition of a given wine 1382:1430 Wine quality improvement did not correlate with the polysaccharide, protein, mannan, or aromatic compound concentrations, suggesting that the mouthfeel and foaming quality of sparkling wine are very complex properties influenced by other wine compounds and their interactions, as well as probably by the specific chemical composition of a given wine. 27375256 4 26 theme low 666:668 arg1 pH 670:671 low pH 666:671 low pH 666:671 These yeasts killed sensitive strains in killer plate assays done under conditions of low pH and temperature similar to those used in sparkling-wine making, although some strains showed a different killer behaviour during the second fermentation. 27375256 4 27 theme sensitive 600:608 arg1 strains 610:616 sensitive strains 600:616 sensitive strains 600:616 These yeasts killed sensitive strains in killer plate assays done under conditions of low pH and temperature similar to those used in sparkling-wine making, although some strains showed a different killer behaviour during the second fermentation. 27375256 4 28 theme different 768:776 arg1 behaviour 785:793 a different killer behaviour 766:793 a different killer behaviour 766:793 These yeasts killed sensitive strains in killer plate assays done under conditions of low pH and temperature similar to those used in sparkling-wine making, although some strains showed a different killer behaviour during the second fermentation. 27375256 1 29 theme sparkling-wine 144:157 arg1 quality 121:127 The quality 117:127 The quality of traditional sparkling-wine 117:157 The quality of traditional sparkling-wine depends on the aging process in the presence of dead yeast cells. 27375256 4 30 theme pH 670:671 arg1 conditions 652:661 conditions 652:661 conditions of low pH and temperature similar to those used in sparkling-wine making 652:734 These yeasts killed sensitive strains in killer plate assays done under conditions of low pH and temperature similar to those used in sparkling-wine making, although some strains showed a different killer behaviour during the second fermentation. 27375256 1 31 theme dead 207:210 arg1 cells 218:222 dead yeast cells 207:222 dead yeast cells 207:222 The quality of traditional sparkling-wine depends on the aging process in the presence of dead yeast cells. 27375256 0 32 theme Saccharomyces 23:35 arg1 strains 55:61 Saccharomyces cerevisiae killer strains 23:61 Saccharomyces cerevisiae killer strains 23:61 Using mixed inocula of Saccharomyces cerevisiae killer strains to improve the quality of traditional sparkling-wine. 27375256 7 33 theme given 1421:1425 arg1 wine 1427:1430 a given wine 1419:1430 a given wine 1419:1430 Wine quality improvement did not correlate with the polysaccharide, protein, mannan, or aromatic compound concentrations, suggesting that the mouthfeel and foaming quality of sparkling wine are very complex properties influenced by other wine compounds and their interactions, as well as probably by the specific chemical composition of a given wine. 27375256 2 34 theme foam 400:403 arg1 properties 405:414 the wine's foam properties 389:414 the wine's foam properties 389:414 These cells undergo a slow autolysis process thereby releasing some compounds, mostly colloidal polymers such as polysaccharides and mannoproteins, which influence the wine's foam properties and mouthfeel. 27375256 0 35 theme strains 55:61 arg1 inocula 12:18 mixed inocula 6:18 mixed inocula of Saccharomyces cerevisiae killer strains 6:61 Using mixed inocula of Saccharomyces cerevisiae killer strains to improve the quality of traditional sparkling-wine. 27375256 5 36 theme fast 831:834 arg1 effect 843:848 The fast killer effect 827:848 The fast killer effect 827:848 The fast killer effect improved the foam quality and mouthfeel of the mixed-inoculated wines, while the slow killer effect gave small improvements over single-inoculated wines. 27375256 3 37 theme cerevisiae 445:454 arg1 yeasts 463:468 Saccharomyces cerevisiae killer yeasts 431:468 Saccharomyces cerevisiae killer yeasts 431:468 Saccharomyces cerevisiae killer yeasts were tested to increase cell death and autolysis during mixed-yeast-inoculated second fermentation and aging. 27375256 5 38 theme killer 936:941 arg1 effect 943:948 the slow killer effect 927:948 the slow killer effect 927:948 The fast killer effect improved the foam quality and mouthfeel of the mixed-inoculated wines, while the slow killer effect gave small improvements over single-inoculated wines. 27375256 0 39 theme killer 48:53 arg1 strains 55:61 Saccharomyces cerevisiae killer strains 23:61 Saccharomyces cerevisiae killer strains 23:61 Using mixed inocula of Saccharomyces cerevisiae killer strains to improve the quality of traditional sparkling-wine. 27375256 0 40 dep Saccharomyces 23:35 arg1 cerevisiae 37:46 cerevisiae 37:46 cerevisiae 37:46 Using mixed inocula of Saccharomyces cerevisiae killer strains to improve the quality of traditional sparkling-wine. 27375256 7 41 theme other 1314:1318 arg1 compounds 1325:1333 other wine compounds 1314:1333 other wine compounds 1314:1333 Wine quality improvement did not correlate with the polysaccharide, protein, mannan, or aromatic compound concentrations, suggesting that the mouthfeel and foaming quality of sparkling wine are very complex properties influenced by other wine compounds and their interactions, as well as probably by the specific chemical composition of a given wine. 27375256 7 42 theme Wine 1082:1085 arg1 improvement 1095:1105 Wine quality improvement 1082:1105 Wine quality improvement 1082:1105 Wine quality improvement did not correlate with the polysaccharide, protein, mannan, or aromatic compound concentrations, suggesting that the mouthfeel and foaming quality of sparkling wine are very complex properties influenced by other wine compounds and their interactions, as well as probably by the specific chemical composition of a given wine. 27375256 2 43 theme autolysis 252:260 arg1 process 262:268 a slow autolysis process 245:268 a slow autolysis process 245:268 These cells undergo a slow autolysis process thereby releasing some compounds, mostly colloidal polymers such as polysaccharides and mannoproteins, which influence the wine's foam properties and mouthfeel. 27375256 7 44 theme wine 1320:1323 arg1 compounds 1325:1333 other wine compounds 1314:1333 other wine compounds 1314:1333 Wine quality improvement did not correlate with the polysaccharide, protein, mannan, or aromatic compound concentrations, suggesting that the mouthfeel and foaming quality of sparkling wine are very complex properties influenced by other wine compounds and their interactions, as well as probably by the specific chemical composition of a given wine. 27375256 5 45 theme single-inoculated 979:995 arg1 wines 997:1001 single-inoculated wines 979:1001 single-inoculated wines 979:1001 The fast killer effect improved the foam quality and mouthfeel of the mixed-inoculated wines, while the slow killer effect gave small improvements over single-inoculated wines. 27375256 1 46 theme cells 218:222 arg1 presence 195:202 the presence 191:202 the presence of dead yeast cells 191:222 The quality of traditional sparkling-wine depends on the aging process in the presence of dead yeast cells. 27375256 7 47 theme quality 1087:1093 arg1 improvement 1095:1105 Wine quality improvement 1082:1105 Wine quality improvement 1082:1105 Wine quality improvement did not correlate with the polysaccharide, protein, mannan, or aromatic compound concentrations, suggesting that the mouthfeel and foaming quality of sparkling wine are very complex properties influenced by other wine compounds and their interactions, as well as probably by the specific chemical composition of a given wine. 27375256 2 48 theme slow 247:250 arg1 process 262:268 a slow autolysis process 245:268 a slow autolysis process 245:268 These cells undergo a slow autolysis process thereby releasing some compounds, mostly colloidal polymers such as polysaccharides and mannoproteins, which influence the wine's foam properties and mouthfeel. 27375256 1 49 theme traditional 132:142 arg1 sparkling-wine 144:157 traditional sparkling-wine 132:157 traditional sparkling-wine 132:157 The quality of traditional sparkling-wine depends on the aging process in the presence of dead yeast cells. 27375256 7 50 theme complex 1281:1287 arg1 properties 1289:1298 very complex properties 1276:1298 very complex properties influenced by other wine compounds and their interactions, as well as probably by the specific chemical composition of a given wine 1276:1430 Wine quality improvement did not correlate with the polysaccharide, protein, mannan, or aromatic compound concentrations, suggesting that the mouthfeel and foaming quality of sparkling wine are very complex properties influenced by other wine compounds and their interactions, as well as probably by the specific chemical composition of a given wine. 27375256 7 50 theme complex 1281:1287 arg1 quality 1246:1252 the mouthfeel and foaming quality 1220:1252 the mouthfeel and foaming quality of sparkling wine 1220:1270 Wine quality improvement did not correlate with the polysaccharide, protein, mannan, or aromatic compound concentrations, suggesting that the mouthfeel and foaming quality of sparkling wine are very complex properties influenced by other wine compounds and their interactions, as well as probably by the specific chemical composition of a given wine. 27375256 1 51 theme yeast 212:216 arg1 cells 218:222 dead yeast cells 207:222 dead yeast cells 207:222 The quality of traditional sparkling-wine depends on the aging process in the presence of dead yeast cells. 27375256 7 52 theme specific 1386:1393 arg1 composition 1404:1414 the specific chemical composition 1382:1414 the specific chemical composition of a given wine 1382:1430 Wine quality improvement did not correlate with the polysaccharide, protein, mannan, or aromatic compound concentrations, suggesting that the mouthfeel and foaming quality of sparkling wine are very complex properties influenced by other wine compounds and their interactions, as well as probably by the specific chemical composition of a given wine. 27375256 5 53 theme foam 863:866 arg1 quality 868:874 foam quality 863:874 foam quality 863:874 The fast killer effect improved the foam quality and mouthfeel of the mixed-inoculated wines, while the slow killer effect gave small improvements over single-inoculated wines. 27375256 3 54 theme mixed-yeast-inoculated 526:547 arg1 fermentation 556:567 mixed-yeast-inoculated second fermentation 526:567 mixed-yeast-inoculated second fermentation 526:567 Saccharomyces cerevisiae killer yeasts were tested to increase cell death and autolysis during mixed-yeast-inoculated second fermentation and aging. 27375256 4 55 theme temperature 677:687 arg1 conditions 652:661 conditions 652:661 conditions of low pH and temperature similar to those used in sparkling-wine making 652:734 These yeasts killed sensitive strains in killer plate assays done under conditions of low pH and temperature similar to those used in sparkling-wine making, although some strains showed a different killer behaviour during the second fermentation. 27375256 6 56 theme low-pressure 1057:1068 arg1 conditions 1070:1079 low-pressure conditions 1057:1079 low-pressure conditions 1057:1079 The effect was faster under high-pressure than under low-pressure conditions. 27375256 7 57 theme compound 1179:1186 arg1 concentrations 1188:1201 aromatic compound concentrations 1170:1201 aromatic compound concentrations 1170:1201 Wine quality improvement did not correlate with the polysaccharide, protein, mannan, or aromatic compound concentrations, suggesting that the mouthfeel and foaming quality of sparkling wine are very complex properties influenced by other wine compounds and their interactions, as well as probably by the specific chemical composition of a given wine. 27375256 5 58 dep quality 868:874 arg1 the 859:861 the 859:861 the 859:861 The fast killer effect improved the foam quality and mouthfeel of the mixed-inoculated wines, while the slow killer effect gave small improvements over single-inoculated wines. 27375256 3 59 theme second 549:554 arg1 fermentation 556:567 mixed-yeast-inoculated second fermentation 526:567 mixed-yeast-inoculated second fermentation 526:567 Saccharomyces cerevisiae killer yeasts were tested to increase cell death and autolysis during mixed-yeast-inoculated second fermentation and aging. 26900400 13 0 theme sugar 1868:1872 arg1 pulp 1879:1882 sugar beet pulp 1868:1882 sugar beet pulp 1868:1882 Supplementing Axe1 to CBS 203.75 enzyme set improved release of xylose and glucose from sugar beet pulp. 26900400 11 1 theme CE5-CBM1 1569:1576 arg1 enzyme 1578:1583 This CE5-CBM1 enzyme 1564:1583 This CE5-CBM1 enzyme 1564:1583 This CE5-CBM1 enzyme, named as Axe1, was phylogenetically related to acetyl xylan esterases. 26900400 8 2 theme altered 1213:1219 arg1 activities 1221:1230 altered activities 1213:1230 altered activities of the major (hemi-)cellulases 1213:1261 The improved SBP saccharification was not explained by altered activities of the major (hemi-)cellulases. 26900400 6 3 theme beet 973:976 arg1 pulp 978:981 sugar beet pulp 967:981 sugar beet pulp 967:981 RESULTS Two genetically diverse M. heterothallica strains CBS 203.75 and CBS 663.74 were used to generate progenies with improved growth on sugar beet pulp. 26900400 6 4 dep RESULTS 827:833 arg1 strains 877:883 Two genetically diverse M. heterothallica strains 835:883 RESULTS Two genetically diverse M. heterothallica strains CBS 203.75 and CBS 663.74 827:909 RESULTS Two genetically diverse M. heterothallica strains CBS 203.75 and CBS 663.74 were used to generate progenies with improved growth on sugar beet pulp. 26900400 5 5 theme fungus 702:707 arg1 heterothallica 724:737 the thermophilic fungus Myceliophthora heterothallica 685:737 the thermophilic fungus Myceliophthora heterothallica 685:737 This study describes a strategy using sexual crossing and screening with the thermophilic fungus Myceliophthora heterothallica to identify specific enzymes associated with improved sugar beet pulp saccharification. 26900400 14 6 theme beneficial 1919:1928 arg1 enzymes 1930:1936 beneficial enzymes 1919:1936 beneficial enzymes for sugar beet pulp saccharification 1919:1973 CONCLUSIONS This study identified beneficial enzymes for sugar beet pulp saccharification by selecting progeny with improved growth on this particular substrate. 26900400 13 7 theme xylose 1844:1849 arg1 release 1833:1839 release 1833:1839 release of xylose and glucose from sugar beet pulp 1833:1882 Supplementing Axe1 to CBS 203.75 enzyme set improved release of xylose and glucose from sugar beet pulp. 26900400 6 8 theme heterothallica 862:875 arg1 strains 877:883 Two genetically diverse M. heterothallica strains 835:883 RESULTS Two genetically diverse M. heterothallica strains CBS 203.75 and CBS 663.74 827:909 RESULTS Two genetically diverse M. heterothallica strains CBS 203.75 and CBS 663.74 were used to generate progenies with improved growth on sugar beet pulp. 26900400 2 9 theme large 294:298 arg1 enzymes 307:313 enzymes 307:313 enzymes targeting different linkages in plant polysaccharides 307:367 Like most fungi, thermophilic Myceliophthora species therefore have a large set of enzymes targeting different linkages in plant polysaccharides. 26900400 2 9 theme large 294:298 arg1 set 300:302 a large set 292:302 a large set of enzymes targeting different linkages in plant polysaccharides 292:367 Like most fungi, thermophilic Myceliophthora species therefore have a large set of enzymes targeting different linkages in plant polysaccharides. 26900400 8 10 theme major 1239:1243 arg1 cellulases 1252:1261 the major (hemi-)cellulases 1235:1261 the major (hemi-)cellulases 1235:1261 The improved SBP saccharification was not explained by altered activities of the major (hemi-)cellulases. 26900400 6 11 theme improved 948:955 arg1 growth 957:962 improved growth 948:962 improved growth on sugar beet pulp 948:981 RESULTS Two genetically diverse M. heterothallica strains CBS 203.75 and CBS 663.74 were used to generate progenies with improved growth on sugar beet pulp. 26900400 16 12 theme sexual 2211:2216 arg1 strategy 2281:2288 the successful strategy 2266:2288 the successful strategy to improve the composition of enzyme mixtures for efficient plant biomass degradation 2266:2374 This shows that sexual crossing and selection of M. heterothallica are the successful strategy to improve the composition of enzyme mixtures for efficient plant biomass degradation. 26900400 16 12 theme sexual 2211:2216 arg1 selection 2231:2239 selection 2231:2239 selection of M. heterothallica 2231:2260 This shows that sexual crossing and selection of M. heterothallica are the successful strategy to improve the composition of enzyme mixtures for efficient plant biomass degradation. 26900400 16 12 theme sexual 2211:2216 arg1 crossing 2218:2225 sexual crossing 2211:2225 sexual crossing 2211:2225 This shows that sexual crossing and selection of M. heterothallica are the successful strategy to improve the composition of enzyme mixtures for efficient plant biomass degradation. 26900400 7 13 theme sugar 1141:1145 arg1 pulp 1152:1155 3 % sugar beet pulp 1137:1155 3 % sugar beet pulp 1137:1155 One progeny, named SBP.F1.2.11, had a different genetic pattern from the parental strains and had improved saccharification activity after the growth on 3 % sugar beet pulp. 26900400 6 14 theme diverse 851:857 arg1 strains 877:883 Two genetically diverse M. heterothallica strains 835:883 RESULTS Two genetically diverse M. heterothallica strains CBS 203.75 and CBS 663.74 827:909 RESULTS Two genetically diverse M. heterothallica strains CBS 203.75 and CBS 663.74 were used to generate progenies with improved growth on sugar beet pulp. 26900400 1 15 theme different 205:213 arg1 enzymes 215:221 many different enzymes 200:221 many different enzymes 200:221 BACKGROUND Enzymatic degradation of plant biomass requires a complex mixture of many different enzymes. 26900400 8 16 theme hemi- 1246:1250 arg1 cellulases 1252:1261 the major (hemi-)cellulases 1235:1261 the major (hemi-)cellulases 1235:1261 The improved SBP saccharification was not explained by altered activities of the major (hemi-)cellulases. 26900400 7 17 theme 3  1137:1138 arg1 % 1139:1139 % 1139:1139 % 1139:1139 One progeny, named SBP.F1.2.11, had a different genetic pattern from the parental strains and had improved saccharification activity after the growth on 3 % sugar beet pulp. 26900400 14 18 theme sugar 1942:1946 arg1 saccharification 1958:1973 sugar beet pulp saccharification 1942:1973 sugar beet pulp saccharification 1942:1973 CONCLUSIONS This study identified beneficial enzymes for sugar beet pulp saccharification by selecting progeny with improved growth on this particular substrate. 26900400 8 19 theme cellulases 1252:1261 arg1 activities 1221:1230 altered activities 1213:1230 altered activities of the major (hemi-)cellulases 1213:1261 The improved SBP saccharification was not explained by altered activities of the major (hemi-)cellulases. 26900400 9 20 theme progeny 1289:1295 arg1 analysis 1277:1284 Exo-proteome analysis 1264:1284 Exo-proteome analysis of progeny and parental strains after 7-day growth on sugar beet pulp 1264:1354 Exo-proteome analysis of progeny and parental strains after 7-day growth on sugar beet pulp showed that only 17 of the 133 secreted CAZy enzymes were more abundant in progeny SBP.F1.2.11. 26900400 2 21 theme thermophilic 241:252 arg1 species 269:275 thermophilic Myceliophthora species 241:275 thermophilic Myceliophthora species 241:275 Like most fungi, thermophilic Myceliophthora species therefore have a large set of enzymes targeting different linkages in plant polysaccharides. 26900400 9 22 from growth 1330:1335 arg1 pulp 1351:1354 sugar beet pulp 1340:1354 sugar beet pulp 1340:1354 Exo-proteome analysis of progeny and parental strains after 7-day growth on sugar beet pulp showed that only 17 of the 133 secreted CAZy enzymes were more abundant in progeny SBP.F1.2.11. 26900400 16 23 theme heterothallica 2247:2260 arg1 strategy 2281:2288 the successful strategy 2266:2288 the successful strategy to improve the composition of enzyme mixtures for efficient plant biomass degradation 2266:2374 This shows that sexual crossing and selection of M. heterothallica are the successful strategy to improve the composition of enzyme mixtures for efficient plant biomass degradation. 26900400 16 23 theme heterothallica 2247:2260 arg1 selection 2231:2239 selection 2231:2239 selection of M. heterothallica 2231:2260 This shows that sexual crossing and selection of M. heterothallica are the successful strategy to improve the composition of enzyme mixtures for efficient plant biomass degradation. 26900400 16 23 theme heterothallica 2247:2260 arg1 crossing 2218:2225 sexual crossing 2211:2225 sexual crossing 2211:2225 This shows that sexual crossing and selection of M. heterothallica are the successful strategy to improve the composition of enzyme mixtures for efficient plant biomass degradation. 26900400 9 24 theme parental 1301:1308 arg1 strains 1310:1316 parental strains 1301:1316 parental strains 1301:1316 Exo-proteome analysis of progeny and parental strains after 7-day growth on sugar beet pulp showed that only 17 of the 133 secreted CAZy enzymes were more abundant in progeny SBP.F1.2.11. 26900400 7 25 theme parental 1057:1064 arg1 strains 1066:1072 the parental strains 1053:1072 the parental strains 1053:1072 One progeny, named SBP.F1.2.11, had a different genetic pattern from the parental strains and had improved saccharification activity after the growth on 3 % sugar beet pulp. 26900400 7 26 theme saccharification 1091:1106 arg1 activity 1108:1115 improved saccharification activity 1082:1115 improved saccharification activity 1082:1115 One progeny, named SBP.F1.2.11, had a different genetic pattern from the parental strains and had improved saccharification activity after the growth on 3 % sugar beet pulp. 26900400 1 27 theme plant 156:160 arg1 biomass 162:168 plant biomass 156:168 plant biomass 156:168 BACKGROUND Enzymatic degradation of plant biomass requires a complex mixture of many different enzymes. 26900400 7 28 dep different 1022:1030 arg1 genetic 1032:1038 genetic 1032:1038 genetic 1032:1038 One progeny, named SBP.F1.2.11, had a different genetic pattern from the parental strains and had improved saccharification activity after the growth on 3 % sugar beet pulp. 26900400 0 29 theme enzymatic 78:86 arg1 degradation 88:98 enzymatic degradation 78:98 enzymatic degradation of sugar beet pulp 78:117 Sexual crossing of thermophilic fungus Myceliophthora heterothallica improved enzymatic degradation of sugar beet pulp. 26900400 14 30 from growth 2010:2015 arg1 substrate 2036:2044 this particular substrate 2020:2044 this particular substrate 2020:2044 CONCLUSIONS This study identified beneficial enzymes for sugar beet pulp saccharification by selecting progeny with improved growth on this particular substrate. 26900400 12 31 theme optimal 1733:1739 arg1 activities 1741:1750 optimal activities 1733:1750 optimal activities at 75-85 °C and pH 5.5-6.0 1733:1777 Biochemical characterization of Axe1 confirmed de-acetylation activity with optimal activities at 75-85 °C and pH 5.5-6.0. 26900400 9 32 theme sugar 1340:1344 arg1 pulp 1351:1354 sugar beet pulp 1340:1354 sugar beet pulp 1340:1354 Exo-proteome analysis of progeny and parental strains after 7-day growth on sugar beet pulp showed that only 17 of the 133 secreted CAZy enzymes were more abundant in progeny SBP.F1.2.11. 26900400 1 33 theme complex 181:187 arg1 mixture 189:195 a complex mixture 179:195 a complex mixture of many different enzymes 179:221 BACKGROUND Enzymatic degradation of plant biomass requires a complex mixture of many different enzymes. 26900400 0 34 theme beet 109:112 arg1 pulp 114:117 sugar beet pulp 103:117 sugar beet pulp 103:117 Sexual crossing of thermophilic fungus Myceliophthora heterothallica improved enzymatic degradation of sugar beet pulp. 26900400 15 35 theme uncharacterized 2147:2161 arg1 esterase 2185:2192 a previously uncharacterized CE5-CBM1 acetyl xylan esterase 2134:2192 a previously uncharacterized CE5-CBM1 acetyl xylan esterase 2134:2192 Saccharification of sugar beet pulp was improved by supplementing enzyme mixtures with a previously uncharacterized CE5-CBM1 acetyl xylan esterase. 26900400 16 36 theme enzyme 2320:2325 arg1 mixtures 2327:2334 enzyme mixtures 2320:2334 enzyme mixtures 2320:2334 This shows that sexual crossing and selection of M. heterothallica are the successful strategy to improve the composition of enzyme mixtures for efficient plant biomass degradation. 26900400 3 37 theme plant 460:464 arg1 degradation 474:484 plant biomass degradation 460:484 plant biomass degradation 460:484 The majority of these enzymes have not been functionally characterized, and their role in plant biomass degradation is unknown. 26900400 5 38 theme pulp 804:807 arg1 saccharification 809:824 improved sugar beet pulp saccharification 784:824 improved sugar beet pulp saccharification 784:824 This study describes a strategy using sexual crossing and screening with the thermophilic fungus Myceliophthora heterothallica to identify specific enzymes associated with improved sugar beet pulp saccharification. 26900400 10 39 theme esterase 1506:1513 arg1 family 1515:1520 the carbohydrate esterase family 5 1489:1522 the carbohydrate esterase family 5 (CE5) 1489:1528 Particularly one enzyme belonging to the carbohydrate esterase family 5 (CE5) was more abundant in SBP.F1.2.11. 26900400 10 39 theme esterase 1506:1513 arg1 CE5 1525:1527 CE5 1525:1527 CE5 1525:1527 Particularly one enzyme belonging to the carbohydrate esterase family 5 (CE5) was more abundant in SBP.F1.2.11. 26900400 0 40 theme Sexual 0:5 arg1 crossing 7:14 Sexual crossing 0:14 Sexual crossing of thermophilic fungus Myceliophthora heterothallica 0:67 Sexual crossing of thermophilic fungus Myceliophthora heterothallica improved enzymatic degradation of sugar beet pulp. 26900400 7 41 theme beet 1147:1150 arg1 pulp 1152:1155 3 % sugar beet pulp 1137:1155 3 % sugar beet pulp 1137:1155 One progeny, named SBP.F1.2.11, had a different genetic pattern from the parental strains and had improved saccharification activity after the growth on 3 % sugar beet pulp. 26900400 12 42 theme Biochemical 1657:1667 arg1 characterization 1669:1684 Biochemical characterization 1657:1684 Biochemical characterization of Axe1 1657:1692 Biochemical characterization of Axe1 confirmed de-acetylation activity with optimal activities at 75-85 °C and pH 5.5-6.0. 26900400 6 43 with progenies 933:941 arg1 growth 957:962 improved growth 948:962 improved growth on sugar beet pulp 948:981 RESULTS Two genetically diverse M. heterothallica strains CBS 203.75 and CBS 663.74 were used to generate progenies with improved growth on sugar beet pulp. 26900400 16 44 theme plant 2350:2354 arg1 degradation 2364:2374 efficient plant biomass degradation 2340:2374 efficient plant biomass degradation 2340:2374 This shows that sexual crossing and selection of M. heterothallica are the successful strategy to improve the composition of enzyme mixtures for efficient plant biomass degradation. 26900400 6 45 used used 916:919 arg2 RESULTS 827:833 RESULTS 827:833 RESULTS Two genetically diverse M. heterothallica strains CBS 203.75 and CBS 663.74 827:909 RESULTS Two genetically diverse M. heterothallica strains CBS 203.75 and CBS 663.74 were used to generate progenies with improved growth on sugar beet pulp. 26900400 1 46 theme BACKGROUND 120:129 arg1 degradation 141:151 BACKGROUND Enzymatic degradation 120:151 BACKGROUND Enzymatic degradation of plant biomass 120:168 BACKGROUND Enzymatic degradation of plant biomass requires a complex mixture of many different enzymes. 26900400 15 47 theme beet 2073:2076 arg1 pulp 2078:2081 sugar beet pulp 2067:2081 sugar beet pulp 2067:2081 Saccharification of sugar beet pulp was improved by supplementing enzyme mixtures with a previously uncharacterized CE5-CBM1 acetyl xylan esterase. 26900400 9 48 theme secreted 1387:1394 arg1 enzymes 1401:1407 the 133 secreted CAZy enzymes 1379:1407 the 133 secreted CAZy enzymes 1379:1407 Exo-proteome analysis of progeny and parental strains after 7-day growth on sugar beet pulp showed that only 17 of the 133 secreted CAZy enzymes were more abundant in progeny SBP.F1.2.11. 26900400 14 49 theme particular 2025:2034 arg1 substrate 2036:2044 this particular substrate 2020:2044 this particular substrate 2020:2044 CONCLUSIONS This study identified beneficial enzymes for sugar beet pulp saccharification by selecting progeny with improved growth on this particular substrate. 26900400 0 50 theme heterothallica 54:67 arg1 crossing 7:14 Sexual crossing 0:14 Sexual crossing of thermophilic fungus Myceliophthora heterothallica 0:67 Sexual crossing of thermophilic fungus Myceliophthora heterothallica improved enzymatic degradation of sugar beet pulp. 26900400 9 51 theme enzymes 1401:1407 arg1 17 1373:1374 17 1373:1374 17 1373:1374 Exo-proteome analysis of progeny and parental strains after 7-day growth on sugar beet pulp showed that only 17 of the 133 secreted CAZy enzymes were more abundant in progeny SBP.F1.2.11. 26900400 9 51 theme enzymes 1401:1407 arg1 enzymes 1401:1407 the 133 secreted CAZy enzymes 1379:1407 the 133 secreted CAZy enzymes 1379:1407 Exo-proteome analysis of progeny and parental strains after 7-day growth on sugar beet pulp showed that only 17 of the 133 secreted CAZy enzymes were more abundant in progeny SBP.F1.2.11. 26900400 9 52 from progeny 1431:1437 arg1 abundant 1419:1426 abundant 1419:1426 abundant 1419:1426 Exo-proteome analysis of progeny and parental strains after 7-day growth on sugar beet pulp showed that only 17 of the 133 secreted CAZy enzymes were more abundant in progeny SBP.F1.2.11. 26900400 13 53 from pulp 1879:1882 arg1 release 1833:1839 release 1833:1839 release of xylose and glucose from sugar beet pulp 1833:1882 Supplementing Axe1 to CBS 203.75 enzyme set improved release of xylose and glucose from sugar beet pulp. 26900400 5 54 with screening 670:678 arg1 heterothallica 724:737 the thermophilic fungus Myceliophthora heterothallica 685:737 the thermophilic fungus Myceliophthora heterothallica 685:737 This study describes a strategy using sexual crossing and screening with the thermophilic fungus Myceliophthora heterothallica to identify specific enzymes associated with improved sugar beet pulp saccharification. 26900400 4 55 theme enzymes 559:565 arg1 enzymes 559:565 enzymes 559:565 enzymes 559:565 The biotechnological challenge is to select the right set of enzymes to efficiently degrade a particular biomass. 26900400 4 55 theme enzymes 559:565 arg1 set 552:554 the right set 542:554 the right set of enzymes to efficiently degrade a particular biomass 542:609 The biotechnological challenge is to select the right set of enzymes to efficiently degrade a particular biomass. 26900400 14 56 dep CONCLUSIONS 1885:1895 arg1 identified 1908:1917 identified 1908:1917 identified beneficial enzymes for sugar beet pulp saccharification by selecting progeny with improved growth on this particular substrate 1908:2044 CONCLUSIONS This study identified beneficial enzymes for sugar beet pulp saccharification by selecting progeny with improved growth on this particular substrate. 26900400 8 57 theme improved 1162:1169 arg1 saccharification 1175:1190 The improved SBP saccharification 1158:1190 The improved SBP saccharification 1158:1190 The improved SBP saccharification was not explained by altered activities of the major (hemi-)cellulases. 26900400 14 58 theme improved 2001:2008 arg1 growth 2010:2015 improved growth 2001:2015 improved growth on this particular substrate 2001:2044 CONCLUSIONS This study identified beneficial enzymes for sugar beet pulp saccharification by selecting progeny with improved growth on this particular substrate. 26900400 16 59 theme successful 2270:2279 arg1 strategy 2281:2288 the successful strategy 2266:2288 the successful strategy to improve the composition of enzyme mixtures for efficient plant biomass degradation 2266:2374 This shows that sexual crossing and selection of M. heterothallica are the successful strategy to improve the composition of enzyme mixtures for efficient plant biomass degradation. 26900400 16 59 theme successful 2270:2279 arg1 selection 2231:2239 selection 2231:2239 selection of M. heterothallica 2231:2260 This shows that sexual crossing and selection of M. heterothallica are the successful strategy to improve the composition of enzyme mixtures for efficient plant biomass degradation. 26900400 16 59 theme successful 2270:2279 arg1 crossing 2218:2225 sexual crossing 2211:2225 sexual crossing 2211:2225 This shows that sexual crossing and selection of M. heterothallica are the successful strategy to improve the composition of enzyme mixtures for efficient plant biomass degradation. 26900400 15 60 theme acetyl 2172:2177 arg1 esterase 2185:2192 a previously uncharacterized CE5-CBM1 acetyl xylan esterase 2134:2192 a previously uncharacterized CE5-CBM1 acetyl xylan esterase 2134:2192 Saccharification of sugar beet pulp was improved by supplementing enzyme mixtures with a previously uncharacterized CE5-CBM1 acetyl xylan esterase. 26900400 11 61 theme acetyl 1633:1638 arg1 esterases 1646:1654 acetyl xylan esterases 1633:1654 acetyl xylan esterases 1633:1654 This CE5-CBM1 enzyme, named as Axe1, was phylogenetically related to acetyl xylan esterases. 26900400 7 62 from growth 1127:1132 arg1 pulp 1152:1155 3 % sugar beet pulp 1137:1155 3 % sugar beet pulp 1137:1155 One progeny, named SBP.F1.2.11, had a different genetic pattern from the parental strains and had improved saccharification activity after the growth on 3 % sugar beet pulp. 26900400 6 63 from growth 957:962 arg1 pulp 978:981 sugar beet pulp 967:981 sugar beet pulp 967:981 RESULTS Two genetically diverse M. heterothallica strains CBS 203.75 and CBS 663.74 were used to generate progenies with improved growth on sugar beet pulp. 26900400 5 64 theme thermophilic 689:700 arg1 heterothallica 724:737 the thermophilic fungus Myceliophthora heterothallica 685:737 the thermophilic fungus Myceliophthora heterothallica 685:737 This study describes a strategy using sexual crossing and screening with the thermophilic fungus Myceliophthora heterothallica to identify specific enzymes associated with improved sugar beet pulp saccharification. 26900400 2 65 theme enzymes 307:313 arg1 enzymes 307:313 enzymes 307:313 enzymes targeting different linkages in plant polysaccharides 307:367 Like most fungi, thermophilic Myceliophthora species therefore have a large set of enzymes targeting different linkages in plant polysaccharides. 26900400 2 65 theme enzymes 307:313 arg1 set 300:302 a large set 292:302 a large set of enzymes targeting different linkages in plant polysaccharides 292:367 Like most fungi, thermophilic Myceliophthora species therefore have a large set of enzymes targeting different linkages in plant polysaccharides. 26900400 2 66 contain have 287:290 arg2 enzymes 307:313 enzymes 307:313 enzymes targeting different linkages in plant polysaccharides 307:367 Like most fungi, thermophilic Myceliophthora species therefore have a large set of enzymes targeting different linkages in plant polysaccharides. 26900400 2 66 contain have 287:290 arg2 set 300:302 a large set 292:302 a large set of enzymes targeting different linkages in plant polysaccharides 292:367 Like most fungi, thermophilic Myceliophthora species therefore have a large set of enzymes targeting different linkages in plant polysaccharides. 26900400 2 66 contain have 287:290 arg1 species 269:275 thermophilic Myceliophthora species 241:275 thermophilic Myceliophthora species 241:275 Like most fungi, thermophilic Myceliophthora species therefore have a large set of enzymes targeting different linkages in plant polysaccharides. 26900400 6 67 theme sugar 967:971 arg1 beet 973:976 sugar beet 967:976 sugar beet pulp 967:981 RESULTS Two genetically diverse M. heterothallica strains CBS 203.75 and CBS 663.74 were used to generate progenies with improved growth on sugar beet pulp. 26900400 7 68 contain had 1078:1080 arg1 progeny 988:994 One progeny 984:994 One progeny 984:994 One progeny, named SBP.F1.2.11, had a different genetic pattern from the parental strains and had improved saccharification activity after the growth on 3 % sugar beet pulp. 26900400 7 68 contain had 1078:1080 arg2 activity 1108:1115 improved saccharification activity 1082:1115 improved saccharification activity 1082:1115 One progeny, named SBP.F1.2.11, had a different genetic pattern from the parental strains and had improved saccharification activity after the growth on 3 % sugar beet pulp. 26900400 5 69 theme sexual 650:655 arg1 crossing 657:664 sexual crossing 650:664 sexual crossing 650:664 This study describes a strategy using sexual crossing and screening with the thermophilic fungus Myceliophthora heterothallica to identify specific enzymes associated with improved sugar beet pulp saccharification. 26900400 13 70 theme CBS 1802:1804 arg1 set 1820:1822 CBS 203.75 enzyme set 1802:1822 CBS 203.75 enzyme set 1802:1822 Supplementing Axe1 to CBS 203.75 enzyme set improved release of xylose and glucose from sugar beet pulp. 26900400 7 71 theme % 1139:1139 arg1 pulp 1152:1155 3 % sugar beet pulp 1137:1155 3 % sugar beet pulp 1137:1155 One progeny, named SBP.F1.2.11, had a different genetic pattern from the parental strains and had improved saccharification activity after the growth on 3 % sugar beet pulp. 26900400 6 72 theme M. 859:860 arg1 strains 877:883 Two genetically diverse M. heterothallica strains 835:883 RESULTS Two genetically diverse M. heterothallica strains CBS 203.75 and CBS 663.74 827:909 RESULTS Two genetically diverse M. heterothallica strains CBS 203.75 and CBS 663.74 were used to generate progenies with improved growth on sugar beet pulp. 26900400 1 73 theme many 200:203 arg1 enzymes 215:221 many different enzymes 200:221 many different enzymes 200:221 BACKGROUND Enzymatic degradation of plant biomass requires a complex mixture of many different enzymes. 26900400 13 74 theme enzyme 1813:1818 arg1 set 1820:1822 CBS 203.75 enzyme set 1802:1822 CBS 203.75 enzyme set 1802:1822 Supplementing Axe1 to CBS 203.75 enzyme set improved release of xylose and glucose from sugar beet pulp. 26900400 5 75 theme specific 751:758 arg1 enzymes 760:766 specific enzymes 751:766 specific enzymes associated with improved sugar beet pulp saccharification 751:824 This study describes a strategy using sexual crossing and screening with the thermophilic fungus Myceliophthora heterothallica to identify specific enzymes associated with improved sugar beet pulp saccharification. 26900400 9 76 theme Exo-proteome 1264:1275 arg1 analysis 1277:1284 Exo-proteome analysis 1264:1284 Exo-proteome analysis of progeny and parental strains after 7-day growth on sugar beet pulp 1264:1354 Exo-proteome analysis of progeny and parental strains after 7-day growth on sugar beet pulp showed that only 17 of the 133 secreted CAZy enzymes were more abundant in progeny SBP.F1.2.11. 26900400 2 77 theme different 325:333 arg1 linkages 335:342 different linkages 325:342 different linkages in plant polysaccharides 325:367 Like most fungi, thermophilic Myceliophthora species therefore have a large set of enzymes targeting different linkages in plant polysaccharides. 26900400 1 78 theme enzymes 215:221 arg1 mixture 189:195 a complex mixture 179:195 a complex mixture of many different enzymes 179:221 BACKGROUND Enzymatic degradation of plant biomass requires a complex mixture of many different enzymes. 26900400 7 79 contain had 1016:1018 arg1 progeny 988:994 One progeny 984:994 One progeny 984:994 One progeny, named SBP.F1.2.11, had a different genetic pattern from the parental strains and had improved saccharification activity after the growth on 3 % sugar beet pulp. 26900400 7 79 contain had 1016:1018 arg2 pattern 1040:1046 a different genetic pattern 1020:1046 a different genetic pattern 1020:1046 One progeny, named SBP.F1.2.11, had a different genetic pattern from the parental strains and had improved saccharification activity after the growth on 3 % sugar beet pulp. 26900400 11 80 theme xylan 1640:1644 arg1 esterases 1646:1654 acetyl xylan esterases 1633:1654 acetyl xylan esterases 1633:1654 This CE5-CBM1 enzyme, named as Axe1, was phylogenetically related to acetyl xylan esterases. 26900400 2 81 theme Myceliophthora 254:267 arg1 species 269:275 thermophilic Myceliophthora species 241:275 thermophilic Myceliophthora species 241:275 Like most fungi, thermophilic Myceliophthora species therefore have a large set of enzymes targeting different linkages in plant polysaccharides. 26900400 14 82 theme pulp 1953:1956 arg1 saccharification 1958:1973 sugar beet pulp saccharification 1942:1973 sugar beet pulp saccharification 1942:1973 CONCLUSIONS This study identified beneficial enzymes for sugar beet pulp saccharification by selecting progeny with improved growth on this particular substrate. 26900400 5 83 with strategy 635:642 arg1 heterothallica 724:737 the thermophilic fungus Myceliophthora heterothallica 685:737 the thermophilic fungus Myceliophthora heterothallica 685:737 This study describes a strategy using sexual crossing and screening with the thermophilic fungus Myceliophthora heterothallica to identify specific enzymes associated with improved sugar beet pulp saccharification. 26900400 12 84 from pH 1768:1769 arg1 activities 1741:1750 optimal activities 1733:1750 optimal activities at 75-85 °C and pH 5.5-6.0 1733:1777 Biochemical characterization of Axe1 confirmed de-acetylation activity with optimal activities at 75-85 °C and pH 5.5-6.0. 26900400 5 85 theme improved 784:791 arg1 saccharification 809:824 improved sugar beet pulp saccharification 784:824 improved sugar beet pulp saccharification 784:824 This study describes a strategy using sexual crossing and screening with the thermophilic fungus Myceliophthora heterothallica to identify specific enzymes associated with improved sugar beet pulp saccharification. 26900400 5 86 theme Myceliophthora 709:722 arg1 heterothallica 724:737 the thermophilic fungus Myceliophthora heterothallica 685:737 the thermophilic fungus Myceliophthora heterothallica 685:737 This study describes a strategy using sexual crossing and screening with the thermophilic fungus Myceliophthora heterothallica to identify specific enzymes associated with improved sugar beet pulp saccharification. 26900400 1 87 theme Enzymatic 131:139 arg1 degradation 141:151 BACKGROUND Enzymatic degradation 120:151 BACKGROUND Enzymatic degradation of plant biomass 120:168 BACKGROUND Enzymatic degradation of plant biomass requires a complex mixture of many different enzymes. 26900400 12 88 from 75-85 °C 1755:1762 arg1 activities 1741:1750 optimal activities 1733:1750 optimal activities at 75-85 °C and pH 5.5-6.0 1733:1777 Biochemical characterization of Axe1 confirmed de-acetylation activity with optimal activities at 75-85 °C and pH 5.5-6.0. 26900400 7 89 theme improved 1082:1089 arg1 activity 1108:1115 improved saccharification activity 1082:1115 improved saccharification activity 1082:1115 One progeny, named SBP.F1.2.11, had a different genetic pattern from the parental strains and had improved saccharification activity after the growth on 3 % sugar beet pulp. 26900400 9 90 theme strains 1310:1316 arg1 analysis 1277:1284 Exo-proteome analysis 1264:1284 Exo-proteome analysis of progeny and parental strains after 7-day growth on sugar beet pulp 1264:1354 Exo-proteome analysis of progeny and parental strains after 7-day growth on sugar beet pulp showed that only 17 of the 133 secreted CAZy enzymes were more abundant in progeny SBP.F1.2.11. 26900400 9 91 theme 7-day 1324:1328 arg1 growth 1330:1335 7-day growth 1324:1335 7-day growth on sugar beet pulp 1324:1354 Exo-proteome analysis of progeny and parental strains after 7-day growth on sugar beet pulp showed that only 17 of the 133 secreted CAZy enzymes were more abundant in progeny SBP.F1.2.11. 26900400 14 92 theme beet 1948:1951 arg1 saccharification 1958:1973 sugar beet pulp saccharification 1942:1973 sugar beet pulp saccharification 1942:1973 CONCLUSIONS This study identified beneficial enzymes for sugar beet pulp saccharification by selecting progeny with improved growth on this particular substrate. 26900400 1 93 theme biomass 162:168 arg1 degradation 141:151 BACKGROUND Enzymatic degradation 120:151 BACKGROUND Enzymatic degradation of plant biomass 120:168 BACKGROUND Enzymatic degradation of plant biomass requires a complex mixture of many different enzymes. 26900400 16 94 theme biomass 2356:2362 arg1 degradation 2364:2374 efficient plant biomass degradation 2340:2374 efficient plant biomass degradation 2340:2374 This shows that sexual crossing and selection of M. heterothallica are the successful strategy to improve the composition of enzyme mixtures for efficient plant biomass degradation. 26900400 5 95 theme sugar 793:797 arg1 saccharification 809:824 improved sugar beet pulp saccharification 784:824 improved sugar beet pulp saccharification 784:824 This study describes a strategy using sexual crossing and screening with the thermophilic fungus Myceliophthora heterothallica to identify specific enzymes associated with improved sugar beet pulp saccharification. 26900400 0 96 theme sugar 103:107 arg1 pulp 114:117 sugar beet pulp 103:117 sugar beet pulp 103:117 Sexual crossing of thermophilic fungus Myceliophthora heterothallica improved enzymatic degradation of sugar beet pulp. 26900400 9 97 from abundant 1419:1426 arg1 progeny 1431:1437 progeny SBP.F1.2.11 1431:1449 progeny SBP.F1.2.11 1431:1449 Exo-proteome analysis of progeny and parental strains after 7-day growth on sugar beet pulp showed that only 17 of the 133 secreted CAZy enzymes were more abundant in progeny SBP.F1.2.11. 26900400 10 98 from abundant 1539:1546 arg1 SBP.F1.2.11 1551:1561 SBP.F1.2.11 1551:1561 SBP.F1.2.11 1551:1561 Particularly one enzyme belonging to the carbohydrate esterase family 5 (CE5) was more abundant in SBP.F1.2.11. 26900400 4 99 theme right 546:550 arg1 enzymes 559:565 enzymes 559:565 enzymes 559:565 The biotechnological challenge is to select the right set of enzymes to efficiently degrade a particular biomass. 26900400 4 99 theme right 546:550 arg1 set 552:554 the right set 542:554 the right set of enzymes to efficiently degrade a particular biomass 542:609 The biotechnological challenge is to select the right set of enzymes to efficiently degrade a particular biomass. 26900400 0 100 theme pulp 114:117 arg1 degradation 88:98 enzymatic degradation 78:98 enzymatic degradation of sugar beet pulp 78:117 Sexual crossing of thermophilic fungus Myceliophthora heterothallica improved enzymatic degradation of sugar beet pulp. 26900400 9 101 theme beet 1346:1349 arg1 pulp 1351:1354 sugar beet pulp 1340:1354 sugar beet pulp 1340:1354 Exo-proteome analysis of progeny and parental strains after 7-day growth on sugar beet pulp showed that only 17 of the 133 secreted CAZy enzymes were more abundant in progeny SBP.F1.2.11. 26900400 7 102 theme different 1022:1030 arg1 pattern 1040:1046 a different genetic pattern 1020:1046 a different genetic pattern 1020:1046 One progeny, named SBP.F1.2.11, had a different genetic pattern from the parental strains and had improved saccharification activity after the growth on 3 % sugar beet pulp. 26900400 2 103 from linkages 335:342 arg1 polysaccharides 353:367 plant polysaccharides 347:367 plant polysaccharides 347:367 Like most fungi, thermophilic Myceliophthora species therefore have a large set of enzymes targeting different linkages in plant polysaccharides. 26900400 10 104 from SBP.F1.2.11 1551:1561 arg1 abundant 1539:1546 abundant 1539:1546 abundant 1539:1546 Particularly one enzyme belonging to the carbohydrate esterase family 5 (CE5) was more abundant in SBP.F1.2.11. 26900400 3 105 theme enzymes 392:398 arg1 majority 374:381 The majority 370:381 The majority of these enzymes 370:398 The majority of these enzymes have not been functionally characterized, and their role in plant biomass degradation is unknown. 26900400 4 106 theme biotechnological 502:517 arg1 challenge 519:527 The biotechnological challenge 498:527 The biotechnological challenge 498:527 The biotechnological challenge is to select the right set of enzymes to efficiently degrade a particular biomass. 26900400 16 107 theme mixtures 2327:2334 arg1 composition 2305:2315 the composition 2301:2315 the composition of enzyme mixtures for efficient plant biomass degradation 2301:2374 This shows that sexual crossing and selection of M. heterothallica are the successful strategy to improve the composition of enzyme mixtures for efficient plant biomass degradation. 26900400 5 108 theme beet 799:802 arg1 saccharification 809:824 improved sugar beet pulp saccharification 784:824 improved sugar beet pulp saccharification 784:824 This study describes a strategy using sexual crossing and screening with the thermophilic fungus Myceliophthora heterothallica to identify specific enzymes associated with improved sugar beet pulp saccharification. 26900400 12 109 theme Axe1 1689:1692 arg1 characterization 1669:1684 Biochemical characterization 1657:1684 Biochemical characterization of Axe1 1657:1692 Biochemical characterization of Axe1 confirmed de-acetylation activity with optimal activities at 75-85 °C and pH 5.5-6.0. 26900400 16 110 theme efficient 2340:2348 arg1 degradation 2364:2374 efficient plant biomass degradation 2340:2374 efficient plant biomass degradation 2340:2374 This shows that sexual crossing and selection of M. heterothallica are the successful strategy to improve the composition of enzyme mixtures for efficient plant biomass degradation. 26900400 3 111 theme biomass 466:472 arg1 degradation 474:484 plant biomass degradation 460:484 plant biomass degradation 460:484 The majority of these enzymes have not been functionally characterized, and their role in plant biomass degradation is unknown. 26900400 15 112 theme enzyme 2113:2118 arg1 mixtures 2120:2127 enzyme mixtures 2113:2127 enzyme mixtures 2113:2127 Saccharification of sugar beet pulp was improved by supplementing enzyme mixtures with a previously uncharacterized CE5-CBM1 acetyl xylan esterase. 26900400 12 113 theme de-acetylation 1704:1717 arg1 activity 1719:1726 de-acetylation activity 1704:1726 de-acetylation activity 1704:1726 Biochemical characterization of Axe1 confirmed de-acetylation activity with optimal activities at 75-85 °C and pH 5.5-6.0. 26900400 10 114 theme carbohydrate 1493:1504 arg1 family 1515:1520 the carbohydrate esterase family 5 1489:1522 the carbohydrate esterase family 5 (CE5) 1489:1528 Particularly one enzyme belonging to the carbohydrate esterase family 5 (CE5) was more abundant in SBP.F1.2.11. 26900400 10 114 theme carbohydrate 1493:1504 arg1 CE5 1525:1527 CE5 1525:1527 CE5 1525:1527 Particularly one enzyme belonging to the carbohydrate esterase family 5 (CE5) was more abundant in SBP.F1.2.11. 26900400 13 115 theme beet 1874:1877 arg1 pulp 1879:1882 sugar beet pulp 1868:1882 sugar beet pulp 1868:1882 Supplementing Axe1 to CBS 203.75 enzyme set improved release of xylose and glucose from sugar beet pulp. 26900400 4 116 theme particular 592:601 arg1 biomass 603:609 a particular biomass 590:609 a particular biomass 590:609 The biotechnological challenge is to select the right set of enzymes to efficiently degrade a particular biomass. 26900400 15 117 theme pulp 2078:2081 arg1 Saccharification 2047:2062 Saccharification 2047:2062 Saccharification of sugar beet pulp 2047:2081 Saccharification of sugar beet pulp was improved by supplementing enzyme mixtures with a previously uncharacterized CE5-CBM1 acetyl xylan esterase. 26900400 9 118 theme CAZy 1396:1399 arg1 enzymes 1401:1407 the 133 secreted CAZy enzymes 1379:1407 the 133 secreted CAZy enzymes 1379:1407 Exo-proteome analysis of progeny and parental strains after 7-day growth on sugar beet pulp showed that only 17 of the 133 secreted CAZy enzymes were more abundant in progeny SBP.F1.2.11. 26900400 15 119 theme sugar 2067:2071 arg1 pulp 2078:2081 sugar beet pulp 2067:2081 sugar beet pulp 2067:2081 Saccharification of sugar beet pulp was improved by supplementing enzyme mixtures with a previously uncharacterized CE5-CBM1 acetyl xylan esterase. 26900400 2 120 theme most 229:232 arg1 fungi 234:238 most fungi 229:238 most fungi 229:238 Like most fungi, thermophilic Myceliophthora species therefore have a large set of enzymes targeting different linkages in plant polysaccharides. 26900400 8 121 theme SBP 1171:1173 arg1 saccharification 1175:1190 The improved SBP saccharification 1158:1190 The improved SBP saccharification 1158:1190 The improved SBP saccharification was not explained by altered activities of the major (hemi-)cellulases. 26900400 15 122 theme xylan 2179:2183 arg1 esterase 2185:2192 a previously uncharacterized CE5-CBM1 acetyl xylan esterase 2134:2192 a previously uncharacterized CE5-CBM1 acetyl xylan esterase 2134:2192 Saccharification of sugar beet pulp was improved by supplementing enzyme mixtures with a previously uncharacterized CE5-CBM1 acetyl xylan esterase. 26900400 3 123 from role 452:455 arg1 degradation 474:484 plant biomass degradation 460:484 plant biomass degradation 460:484 The majority of these enzymes have not been functionally characterized, and their role in plant biomass degradation is unknown. 26900400 2 124 theme plant 347:351 arg1 polysaccharides 353:367 plant polysaccharides 347:367 plant polysaccharides 347:367 Like most fungi, thermophilic Myceliophthora species therefore have a large set of enzymes targeting different linkages in plant polysaccharides. 26900400 6 125 theme CBS 900:902 arg1 663.74 904:909 CBS 663.74 900:909 CBS 663.74 900:909 RESULTS Two genetically diverse M. heterothallica strains CBS 203.75 and CBS 663.74 were used to generate progenies with improved growth on sugar beet pulp. 26900400 15 126 theme CE5-CBM1 2163:2170 arg1 esterase 2185:2192 a previously uncharacterized CE5-CBM1 acetyl xylan esterase 2134:2192 a previously uncharacterized CE5-CBM1 acetyl xylan esterase 2134:2192 Saccharification of sugar beet pulp was improved by supplementing enzyme mixtures with a previously uncharacterized CE5-CBM1 acetyl xylan esterase. 26900400 13 127 theme glucose 1855:1861 arg1 release 1833:1839 release 1833:1839 release of xylose and glucose from sugar beet pulp 1833:1882 Supplementing Axe1 to CBS 203.75 enzyme set improved release of xylose and glucose from sugar beet pulp. 25938477 1 0 from model 303:307 arg1 parasites 238:246 intestinal helminth parasites 218:246 intestinal helminth parasites 218:246 Trichuris species are a globally important and prevalent group of intestinal helminth parasites, in which Trichuris muris (mouse whipworm) is an ideal model for this disease. 25938477 1 0 from model 303:307 arg1 group 209:213 a globally important and prevalent group 174:213 a globally important and prevalent group 174:213 Trichuris species are a globally important and prevalent group of intestinal helminth parasites, in which Trichuris muris (mouse whipworm) is an ideal model for this disease. 25938477 1 0 from model 303:307 arg1 species 162:168 Trichuris species 152:168 Trichuris species 152:168 Trichuris species are a globally important and prevalent group of intestinal helminth parasites, in which Trichuris muris (mouse whipworm) is an ideal model for this disease. 25938477 11 1 from consequences 1872:1883 arg1 microbiota 1905:1914 the microbiota 1901:1914 the microbiota 1901:1914 This reflects the highly regulated chronic response and potential lasting immunological consequences of dysbiosis in the microbiota. 25938477 6 2 theme derived 1160:1166 arg1 carbohydrates 1168:1180 dietary plant derived carbohydrates 1146:1180 dietary plant derived carbohydrates 1146:1180 Metabolomic analysis of stool samples of infected mice at day 41 showed significant differences to uninfected controls with a significant increase in the levels of a number of essential amino acids and a reduction in breakdown of dietary plant derived carbohydrates. 25938477 6 3 theme dietary 1146:1152 arg1 plant 1154:1158 dietary plant 1146:1158 dietary plant 1146:1158 Metabolomic analysis of stool samples of infected mice at day 41 showed significant differences to uninfected controls with a significant increase in the levels of a number of essential amino acids and a reduction in breakdown of dietary plant derived carbohydrates. 25938477 10 4 theme muris 1767:1771 arg1 infection 1773:1781 chronic T. muris infection 1756:1781 chronic T. muris infection 1756:1781 Interestingly this was not observed for all of the key immune cell populations associated with chronic T. muris infection. 25938477 4 5 from Changes 644:650 arg1 composition 665:675 microbial composition 655:675 microbial composition 655:675 Changes in microbial composition occurred between 14 and 28 days post infection, resulting in significant changes in α and β- diversity. 25938477 4 6 theme microbial 655:663 arg1 composition 665:675 microbial composition 655:675 microbial composition 655:675 Changes in microbial composition occurred between 14 and 28 days post infection, resulting in significant changes in α and β- diversity. 25938477 7 7 from reduction 1199:1207 arg1 gain 1219:1222 weight gain 1212:1222 weight gain 1212:1222 The significant reduction in weight gain by infected mice probably reflects these metabolic changes and the incomplete digestion of dietary polysaccharides. 25938477 1 8 theme important 185:193 arg1 parasites 238:246 intestinal helminth parasites 218:246 intestinal helminth parasites 218:246 Trichuris species are a globally important and prevalent group of intestinal helminth parasites, in which Trichuris muris (mouse whipworm) is an ideal model for this disease. 25938477 1 8 theme important 185:193 arg1 group 209:213 a globally important and prevalent group 174:213 a globally important and prevalent group 174:213 Trichuris species are a globally important and prevalent group of intestinal helminth parasites, in which Trichuris muris (mouse whipworm) is an ideal model for this disease. 25938477 1 8 theme important 185:193 arg1 species 162:168 Trichuris species 152:168 Trichuris species 152:168 Trichuris species are a globally important and prevalent group of intestinal helminth parasites, in which Trichuris muris (mouse whipworm) is an ideal model for this disease. 25938477 12 9 theme mice 2039:2042 arg1 microbiota 2002:2011 intestinal microbiota 1991:2011 intestinal microbiota 1991:2011 Thus infection of T. muris causes a significant and substantial impact on intestinal microbiota and digestive function of mice with affects in long term immune regulation. 25938477 12 9 theme mice 2039:2042 arg1 function 2027:2034 digestive function 2017:2034 digestive function 2017:2034 Thus infection of T. muris causes a significant and substantial impact on intestinal microbiota and digestive function of mice with affects in long term immune regulation. 25938477 6 10 theme infected 957:964 arg1 mice 966:969 infected mice 957:969 infected mice 957:969 Metabolomic analysis of stool samples of infected mice at day 41 showed significant differences to uninfected controls with a significant increase in the levels of a number of essential amino acids and a reduction in breakdown of dietary plant derived carbohydrates. 25938477 2 11 theme successful 529:538 arg1 clearance 540:548 successful clearance 529:548 successful clearance of the infection 529:565 This paper describes the first ever highly controlled and comprehensive investigation into the effects of T. muris infection on the faecal microbiota of mice and the effects on the microbiota following successful clearance of the infection. 25938477 11 12 theme chronic 1819:1825 arg1 response 1827:1834 the highly regulated chronic response 1798:1834 the highly regulated chronic response 1798:1834 This reflects the highly regulated chronic response and potential lasting immunological consequences of dysbiosis in the microbiota. 25938477 1 13 theme prevalent 199:207 arg1 parasites 238:246 intestinal helminth parasites 218:246 intestinal helminth parasites 218:246 Trichuris species are a globally important and prevalent group of intestinal helminth parasites, in which Trichuris muris (mouse whipworm) is an ideal model for this disease. 25938477 1 13 theme prevalent 199:207 arg1 group 209:213 a globally important and prevalent group 174:213 a globally important and prevalent group 174:213 Trichuris species are a globally important and prevalent group of intestinal helminth parasites, in which Trichuris muris (mouse whipworm) is an ideal model for this disease. 25938477 1 13 theme prevalent 199:207 arg1 species 162:168 Trichuris species 152:168 Trichuris species 152:168 Trichuris species are a globally important and prevalent group of intestinal helminth parasites, in which Trichuris muris (mouse whipworm) is an ideal model for this disease. 25938477 12 14 theme intestinal 1991:2000 arg1 microbiota 2002:2011 intestinal microbiota 1991:2011 intestinal microbiota 1991:2011 Thus infection of T. muris causes a significant and substantial impact on intestinal microbiota and digestive function of mice with affects in long term immune regulation. 25938477 6 15 theme samples 946:952 arg1 analysis 928:935 Metabolomic analysis 916:935 Metabolomic analysis of stool samples of infected mice at day 41 916:979 Metabolomic analysis of stool samples of infected mice at day 41 showed significant differences to uninfected controls with a significant increase in the levels of a number of essential amino acids and a reduction in breakdown of dietary plant derived carbohydrates. 25938477 6 16 dep derived 1160:1166 arg1 plant 1154:1158 dietary plant 1146:1158 dietary plant 1146:1158 Metabolomic analysis of stool samples of infected mice at day 41 showed significant differences to uninfected controls with a significant increase in the levels of a number of essential amino acids and a reduction in breakdown of dietary plant derived carbohydrates. 25938477 5 17 from reduction 812:820 arg1 diversity 829:837 diversity 829:837 diversity 829:837 This impact was dominated by a reduction in the diversity and abundance of Bacteroidetes, specifically Prevotella and Parabacteroides. 25938477 5 17 from reduction 812:820 arg1 abundance 843:851 abundance 843:851 abundance 843:851 This impact was dominated by a reduction in the diversity and abundance of Bacteroidetes, specifically Prevotella and Parabacteroides. 25938477 2 18 theme infection 557:565 arg1 clearance 540:548 successful clearance 529:548 successful clearance of the infection 529:565 This paper describes the first ever highly controlled and comprehensive investigation into the effects of T. muris infection on the faecal microbiota of mice and the effects on the microbiota following successful clearance of the infection. 25938477 6 19 theme Metabolomic 916:926 arg1 analysis 928:935 Metabolomic analysis 916:935 Metabolomic analysis of stool samples of infected mice at day 41 916:979 Metabolomic analysis of stool samples of infected mice at day 41 showed significant differences to uninfected controls with a significant increase in the levels of a number of essential amino acids and a reduction in breakdown of dietary plant derived carbohydrates. 25938477 8 20 theme uninfected 1489:1498 arg1 animal 1500:1505 an uninfected animal 1486:1505 an uninfected animal 1486:1505 Following clearance of infection the intestinal microbiota underwent additional changes gradually transitioning by day 91 towards a microbiota of an uninfected animal. 25938477 3 21 theme 454 606:608 arg1 pyrosequencing 610:623 454 pyrosequencing 606:623 454 pyrosequencing 606:623 Communities were profiled using DGGE, 454 pyrosequencing, and metabolomics. 25938477 2 22 theme mice 480:483 arg1 microbiota 466:475 the faecal microbiota 455:475 the faecal microbiota of mice 455:483 This paper describes the first ever highly controlled and comprehensive investigation into the effects of T. muris infection on the faecal microbiota of mice and the effects on the microbiota following successful clearance of the infection. 25938477 2 23 from effects 493:499 arg1 microbiota 466:475 the faecal microbiota 455:475 the faecal microbiota of mice 455:483 This paper describes the first ever highly controlled and comprehensive investigation into the effects of T. muris infection on the faecal microbiota of mice and the effects on the microbiota following successful clearance of the infection. 25938477 2 23 from effects 493:499 arg1 microbiota 508:517 the microbiota 504:517 the microbiota following successful clearance of the infection 504:565 This paper describes the first ever highly controlled and comprehensive investigation into the effects of T. muris infection on the faecal microbiota of mice and the effects on the microbiota following successful clearance of the infection. 25938477 7 24 theme incomplete 1291:1300 arg1 digestion 1302:1310 the incomplete digestion 1287:1310 the incomplete digestion of dietary polysaccharides 1287:1337 The significant reduction in weight gain by infected mice probably reflects these metabolic changes and the incomplete digestion of dietary polysaccharides. 25938477 6 25 link derived 1160:1166 arg1 carbohydrates 1168:1180 dietary plant derived carbohydrates 1146:1180 dietary plant derived carbohydrates 1146:1180 Metabolomic analysis of stool samples of infected mice at day 41 showed significant differences to uninfected controls with a significant increase in the levels of a number of essential amino acids and a reduction in breakdown of dietary plant derived carbohydrates. 25938477 0 26 theme Significant 57:67 arg1 Changes 69:75 Significant Changes 57:75 Significant Changes in Host Microbiota and Metabolome: Effects Reversed by Pathogen Clearance 57:149 Chronic Trichuris muris Infection in C57BL/6 Mice Causes Significant Changes in Host Microbiota and Metabolome: Effects Reversed by Pathogen Clearance. 25938477 12 27 with mice 2039:2042 arg1 affects 2049:2055 affects 2049:2055 affects 2049:2055 Thus infection of T. muris causes a significant and substantial impact on intestinal microbiota and digestive function of mice with affects in long term immune regulation. 25938477 5 28 theme Bacteroidetes 856:868 arg1 diversity 829:837 diversity 829:837 diversity 829:837 This impact was dominated by a reduction in the diversity and abundance of Bacteroidetes, specifically Prevotella and Parabacteroides. 25938477 5 28 theme Bacteroidetes 856:868 arg1 abundance 843:851 abundance 843:851 abundance 843:851 This impact was dominated by a reduction in the diversity and abundance of Bacteroidetes, specifically Prevotella and Parabacteroides. 25938477 6 29 theme significant 988:998 arg1 differences 1000:1010 significant differences 988:1010 significant differences 988:1010 Metabolomic analysis of stool samples of infected mice at day 41 showed significant differences to uninfected controls with a significant increase in the levels of a number of essential amino acids and a reduction in breakdown of dietary plant derived carbohydrates. 25938477 12 30 theme significant 1953:1963 arg1 impact 1981:1986 a significant and substantial impact 1951:1986 a significant and substantial impact on intestinal microbiota and digestive function of mice with affects in long term immune regulation 1951:2086 Thus infection of T. muris causes a significant and substantial impact on intestinal microbiota and digestive function of mice with affects in long term immune regulation. 25938477 7 31 theme significant 1187:1197 arg1 reduction 1199:1207 The significant reduction 1183:1207 The significant reduction in weight gain by infected mice 1183:1239 The significant reduction in weight gain by infected mice probably reflects these metabolic changes and the incomplete digestion of dietary polysaccharides. 25938477 12 32 theme substantial 1969:1979 arg1 impact 1981:1986 a significant and substantial impact 1951:1986 a significant and substantial impact on intestinal microbiota and digestive function of mice with affects in long term immune regulation 1951:2086 Thus infection of T. muris causes a significant and substantial impact on intestinal microbiota and digestive function of mice with affects in long term immune regulation. 25938477 4 33 from changes 750:756 arg1 β- 767:768 β- 767:768 β- 767:768 Changes in microbial composition occurred between 14 and 28 days post infection, resulting in significant changes in α and β- diversity. 25938477 4 33 from changes 750:756 arg1 α 761:761 α 761:761 α 761:761 Changes in microbial composition occurred between 14 and 28 days post infection, resulting in significant changes in α and β- diversity. 25938477 6 34 from day 974:976 arg1 analysis 928:935 Metabolomic analysis 916:935 Metabolomic analysis of stool samples of infected mice at day 41 916:979 Metabolomic analysis of stool samples of infected mice at day 41 showed significant differences to uninfected controls with a significant increase in the levels of a number of essential amino acids and a reduction in breakdown of dietary plant derived carbohydrates. 25938477 8 35 theme infection 1363:1371 arg1 clearance 1350:1358 clearance 1350:1358 clearance of infection 1350:1371 Following clearance of infection the intestinal microbiota underwent additional changes gradually transitioning by day 91 towards a microbiota of an uninfected animal. 25938477 2 36 theme controlled 370:379 arg1 investigation 399:411 the first ever highly controlled and comprehensive investigation 348:411 the first ever highly controlled and comprehensive investigation into the effects of T. muris infection on the faecal microbiota of mice and the effects on the microbiota following successful clearance of the infection 348:565 This paper describes the first ever highly controlled and comprehensive investigation into the effects of T. muris infection on the faecal microbiota of mice and the effects on the microbiota following successful clearance of the infection. 25938477 9 37 theme infection 1579:1587 arg1 consequence 1564:1574 a consequence 1562:1574 a consequence of infection 1562:1587 These data indicate that the changes in microbiota as a consequence of infection were transitory requiring the presence of the pathogen for maintenance. 25938477 2 38 theme T. 433:434 arg1 infection 442:450 T. muris infection 433:450 T. muris infection 433:450 This paper describes the first ever highly controlled and comprehensive investigation into the effects of T. muris infection on the faecal microbiota of mice and the effects on the microbiota following successful clearance of the infection. 25938477 8 39 theme intestinal 1377:1386 arg1 microbiota 1388:1397 the intestinal microbiota 1373:1397 the intestinal microbiota 1373:1397 Following clearance of infection the intestinal microbiota underwent additional changes gradually transitioning by day 91 towards a microbiota of an uninfected animal. 25938477 0 40 theme Chronic 0:6 arg1 Infection 24:32 Chronic Trichuris muris Infection 0:32 Chronic Trichuris muris Infection in C57BL/6 Mice 0:48 Chronic Trichuris muris Infection in C57BL/6 Mice Causes Significant Changes in Host Microbiota and Metabolome: Effects Reversed by Pathogen Clearance. 25938477 7 41 theme dietary 1315:1321 arg1 polysaccharides 1323:1337 dietary polysaccharides 1315:1337 dietary polysaccharides 1315:1337 The significant reduction in weight gain by infected mice probably reflects these metabolic changes and the incomplete digestion of dietary polysaccharides. 25938477 11 42 from microbiota 1905:1914 arg1 consequences 1872:1883 immunological consequences 1858:1883 immunological consequences of dysbiosis in the microbiota 1858:1914 This reflects the highly regulated chronic response and potential lasting immunological consequences of dysbiosis in the microbiota. 25938477 0 43 theme muris 18:22 arg1 Infection 24:32 Chronic Trichuris muris Infection 0:32 Chronic Trichuris muris Infection in C57BL/6 Mice 0:48 Chronic Trichuris muris Infection in C57BL/6 Mice Causes Significant Changes in Host Microbiota and Metabolome: Effects Reversed by Pathogen Clearance. 25938477 2 44 theme comprehensive 385:397 arg1 investigation 399:411 the first ever highly controlled and comprehensive investigation 348:411 the first ever highly controlled and comprehensive investigation into the effects of T. muris infection on the faecal microbiota of mice and the effects on the microbiota following successful clearance of the infection 348:565 This paper describes the first ever highly controlled and comprehensive investigation into the effects of T. muris infection on the faecal microbiota of mice and the effects on the microbiota following successful clearance of the infection. 25938477 2 45 theme infection 442:450 arg1 effects 493:499 the effects 489:499 the effects on the microbiota following successful clearance of the infection 489:565 This paper describes the first ever highly controlled and comprehensive investigation into the effects of T. muris infection on the faecal microbiota of mice and the effects on the microbiota following successful clearance of the infection. 25938477 2 45 theme infection 442:450 arg1 effects 422:428 the effects 418:428 the effects of T. muris infection on the faecal microbiota of mice 418:483 This paper describes the first ever highly controlled and comprehensive investigation into the effects of T. muris infection on the faecal microbiota of mice and the effects on the microbiota following successful clearance of the infection. 25938477 1 46 theme ideal 297:301 arg1 muris 268:272 Trichuris muris 258:272 Trichuris muris (mouse whipworm) 258:289 Trichuris species are a globally important and prevalent group of intestinal helminth parasites, in which Trichuris muris (mouse whipworm) is an ideal model for this disease. 25938477 1 46 theme ideal 297:301 arg1 model 303:307 an ideal model 294:307 an ideal model for this disease 294:324 Trichuris species are a globally important and prevalent group of intestinal helminth parasites, in which Trichuris muris (mouse whipworm) is an ideal model for this disease. 25938477 0 47 from Infection 24:32 arg1 Mice 45:48 C57BL/6 Mice 37:48 C57BL/6 Mice 37:48 Chronic Trichuris muris Infection in C57BL/6 Mice Causes Significant Changes in Host Microbiota and Metabolome: Effects Reversed by Pathogen Clearance. 25938477 9 48 theme pathogen 1635:1642 arg1 presence 1619:1626 the presence 1615:1626 the presence of the pathogen 1615:1642 These data indicate that the changes in microbiota as a consequence of infection were transitory requiring the presence of the pathogen for maintenance. 25938477 6 49 theme acids 1108:1112 arg1 number 1082:1087 a number 1080:1087 a number of essential amino acids 1080:1112 Metabolomic analysis of stool samples of infected mice at day 41 showed significant differences to uninfected controls with a significant increase in the levels of a number of essential amino acids and a reduction in breakdown of dietary plant derived carbohydrates. 25938477 10 50 theme immune 1716:1721 arg1 populations 1728:1738 the key immune cell populations 1708:1738 the key immune cell populations associated with chronic T. muris infection 1708:1781 Interestingly this was not observed for all of the key immune cell populations associated with chronic T. muris infection. 25938477 1 51 theme intestinal 218:227 arg1 parasites 238:246 intestinal helminth parasites 218:246 intestinal helminth parasites 218:246 Trichuris species are a globally important and prevalent group of intestinal helminth parasites, in which Trichuris muris (mouse whipworm) is an ideal model for this disease. 25938477 6 52 theme essential 1092:1100 arg1 acids 1108:1112 essential amino acids 1092:1112 essential amino acids 1092:1112 Metabolomic analysis of stool samples of infected mice at day 41 showed significant differences to uninfected controls with a significant increase in the levels of a number of essential amino acids and a reduction in breakdown of dietary plant derived carbohydrates. 25938477 10 53 theme T. 1764:1765 arg1 infection 1773:1781 chronic T. muris infection 1756:1781 chronic T. muris infection 1756:1781 Interestingly this was not observed for all of the key immune cell populations associated with chronic T. muris infection. 25938477 1 54 theme parasites 238:246 arg1 parasites 238:246 intestinal helminth parasites 218:246 intestinal helminth parasites 218:246 Trichuris species are a globally important and prevalent group of intestinal helminth parasites, in which Trichuris muris (mouse whipworm) is an ideal model for this disease. 25938477 1 54 theme parasites 238:246 arg1 group 209:213 a globally important and prevalent group 174:213 a globally important and prevalent group 174:213 Trichuris species are a globally important and prevalent group of intestinal helminth parasites, in which Trichuris muris (mouse whipworm) is an ideal model for this disease. 25938477 1 54 theme parasites 238:246 arg1 species 162:168 Trichuris species 152:168 Trichuris species 152:168 Trichuris species are a globally important and prevalent group of intestinal helminth parasites, in which Trichuris muris (mouse whipworm) is an ideal model for this disease. 25938477 12 55 theme term 2065:2068 arg1 regulation 2077:2086 long term immune regulation 2060:2086 long term immune regulation 2060:2086 Thus infection of T. muris causes a significant and substantial impact on intestinal microbiota and digestive function of mice with affects in long term immune regulation. 25938477 6 56 theme number 1082:1087 arg1 levels 1070:1075 the levels 1066:1075 the levels of a number of essential amino acids 1066:1112 Metabolomic analysis of stool samples of infected mice at day 41 showed significant differences to uninfected controls with a significant increase in the levels of a number of essential amino acids and a reduction in breakdown of dietary plant derived carbohydrates. 25938477 7 57 theme infected 1227:1234 arg1 mice 1236:1239 infected mice 1227:1239 infected mice 1227:1239 The significant reduction in weight gain by infected mice probably reflects these metabolic changes and the incomplete digestion of dietary polysaccharides. 25938477 6 58 from increase 1054:1061 arg1 breakdown 1133:1141 breakdown 1133:1141 breakdown of dietary plant derived carbohydrates 1133:1180 Metabolomic analysis of stool samples of infected mice at day 41 showed significant differences to uninfected controls with a significant increase in the levels of a number of essential amino acids and a reduction in breakdown of dietary plant derived carbohydrates. 25938477 6 58 from increase 1054:1061 arg1 levels 1070:1075 the levels 1066:1075 the levels of a number of essential amino acids 1066:1112 Metabolomic analysis of stool samples of infected mice at day 41 showed significant differences to uninfected controls with a significant increase in the levels of a number of essential amino acids and a reduction in breakdown of dietary plant derived carbohydrates. 25938477 1 59 theme Trichuris 258:266 arg1 whipworm 281:288 mouse whipworm 275:288 mouse whipworm 275:288 Trichuris species are a globally important and prevalent group of intestinal helminth parasites, in which Trichuris muris (mouse whipworm) is an ideal model for this disease. 25938477 1 59 theme Trichuris 258:266 arg1 model 303:307 an ideal model 294:307 an ideal model for this disease 294:324 Trichuris species are a globally important and prevalent group of intestinal helminth parasites, in which Trichuris muris (mouse whipworm) is an ideal model for this disease. 25938477 1 59 theme Trichuris 258:266 arg1 muris 268:272 Trichuris muris 258:272 Trichuris muris (mouse whipworm) 258:289 Trichuris species are a globally important and prevalent group of intestinal helminth parasites, in which Trichuris muris (mouse whipworm) is an ideal model for this disease. 25938477 9 60 from changes 1537:1543 arg1 microbiota 1548:1557 microbiota 1548:1557 microbiota 1548:1557 These data indicate that the changes in microbiota as a consequence of infection were transitory requiring the presence of the pathogen for maintenance. 25938477 12 61 theme digestive 2017:2025 arg1 function 2027:2034 digestive function 2017:2034 digestive function 2017:2034 Thus infection of T. muris causes a significant and substantial impact on intestinal microbiota and digestive function of mice with affects in long term immune regulation. 25938477 6 62 theme mice 966:969 arg1 samples 946:952 stool samples 940:952 stool samples of infected mice 940:969 Metabolomic analysis of stool samples of infected mice at day 41 showed significant differences to uninfected controls with a significant increase in the levels of a number of essential amino acids and a reduction in breakdown of dietary plant derived carbohydrates. 25938477 0 63 theme Pathogen 132:139 arg1 Clearance 141:149 Pathogen Clearance 132:149 Pathogen Clearance 132:149 Chronic Trichuris muris Infection in C57BL/6 Mice Causes Significant Changes in Host Microbiota and Metabolome: Effects Reversed by Pathogen Clearance. 25938477 6 64 theme stool 940:944 arg1 samples 946:952 stool samples 940:952 stool samples of infected mice 940:969 Metabolomic analysis of stool samples of infected mice at day 41 showed significant differences to uninfected controls with a significant increase in the levels of a number of essential amino acids and a reduction in breakdown of dietary plant derived carbohydrates. 25938477 0 65 from Changes 69:75 arg1 Host 80:83 Host Microbiota and Metabolome 80:109 Host 80:83 Chronic Trichuris muris Infection in C57BL/6 Mice Causes Significant Changes in Host Microbiota and Metabolome: Effects Reversed by Pathogen Clearance. 25938477 0 65 from Changes 69:75 arg1 Metabolome 100:109 Metabolome 100:109 Metabolome 100:109 Chronic Trichuris muris Infection in C57BL/6 Mice Causes Significant Changes in Host Microbiota and Metabolome: Effects Reversed by Pathogen Clearance. 25938477 8 66 theme animal 1500:1505 arg1 microbiota 1472:1481 a microbiota 1470:1481 a microbiota of an uninfected animal 1470:1505 Following clearance of infection the intestinal microbiota underwent additional changes gradually transitioning by day 91 towards a microbiota of an uninfected animal. 25938477 11 67 theme immunological 1858:1870 arg1 consequences 1872:1883 immunological consequences 1858:1883 immunological consequences of dysbiosis in the microbiota 1858:1914 This reflects the highly regulated chronic response and potential lasting immunological consequences of dysbiosis in the microbiota. 25938477 6 68 theme uninfected 1015:1024 arg1 controls 1026:1033 uninfected controls 1015:1033 uninfected controls 1015:1033 Metabolomic analysis of stool samples of infected mice at day 41 showed significant differences to uninfected controls with a significant increase in the levels of a number of essential amino acids and a reduction in breakdown of dietary plant derived carbohydrates. 25938477 11 69 theme dysbiosis 1888:1896 arg1 consequences 1872:1883 immunological consequences 1858:1883 immunological consequences of dysbiosis in the microbiota 1858:1914 This reflects the highly regulated chronic response and potential lasting immunological consequences of dysbiosis in the microbiota. 25938477 7 70 theme weight 1212:1217 arg1 gain 1219:1222 weight gain 1212:1222 weight gain 1212:1222 The significant reduction in weight gain by infected mice probably reflects these metabolic changes and the incomplete digestion of dietary polysaccharides. 25938477 4 71 dep α 761:761 arg1 diversity 770:778 diversity 770:778 diversity 770:778 Changes in microbial composition occurred between 14 and 28 days post infection, resulting in significant changes in α and β- diversity. 25938477 2 72 from effects 422:428 arg1 microbiota 466:475 the faecal microbiota 455:475 the faecal microbiota of mice 455:483 This paper describes the first ever highly controlled and comprehensive investigation into the effects of T. muris infection on the faecal microbiota of mice and the effects on the microbiota following successful clearance of the infection. 25938477 2 72 from effects 422:428 arg1 microbiota 508:517 the microbiota 504:517 the microbiota following successful clearance of the infection 504:565 This paper describes the first ever highly controlled and comprehensive investigation into the effects of T. muris infection on the faecal microbiota of mice and the effects on the microbiota following successful clearance of the infection. 25938477 6 73 theme carbohydrates 1168:1180 arg1 breakdown 1133:1141 breakdown 1133:1141 breakdown of dietary plant derived carbohydrates 1133:1180 Metabolomic analysis of stool samples of infected mice at day 41 showed significant differences to uninfected controls with a significant increase in the levels of a number of essential amino acids and a reduction in breakdown of dietary plant derived carbohydrates. 25938477 12 74 from impact 1981:1986 arg1 microbiota 2002:2011 intestinal microbiota 1991:2011 intestinal microbiota 1991:2011 Thus infection of T. muris causes a significant and substantial impact on intestinal microbiota and digestive function of mice with affects in long term immune regulation. 25938477 12 74 from impact 1981:1986 arg1 function 2027:2034 digestive function 2017:2034 digestive function 2017:2034 Thus infection of T. muris causes a significant and substantial impact on intestinal microbiota and digestive function of mice with affects in long term immune regulation. 25938477 1 75 theme Trichuris 152:160 arg1 parasites 238:246 intestinal helminth parasites 218:246 intestinal helminth parasites 218:246 Trichuris species are a globally important and prevalent group of intestinal helminth parasites, in which Trichuris muris (mouse whipworm) is an ideal model for this disease. 25938477 1 75 theme Trichuris 152:160 arg1 group 209:213 a globally important and prevalent group 174:213 a globally important and prevalent group 174:213 Trichuris species are a globally important and prevalent group of intestinal helminth parasites, in which Trichuris muris (mouse whipworm) is an ideal model for this disease. 25938477 1 75 theme Trichuris 152:160 arg1 species 162:168 Trichuris species 152:168 Trichuris species 152:168 Trichuris species are a globally important and prevalent group of intestinal helminth parasites, in which Trichuris muris (mouse whipworm) is an ideal model for this disease. 25938477 2 76 theme faecal 459:464 arg1 microbiota 466:475 the faecal microbiota 455:475 the faecal microbiota of mice 455:483 This paper describes the first ever highly controlled and comprehensive investigation into the effects of T. muris infection on the faecal microbiota of mice and the effects on the microbiota following successful clearance of the infection. 25938477 11 77 theme regulated 1809:1817 arg1 response 1827:1834 the highly regulated chronic response 1798:1834 the highly regulated chronic response 1798:1834 This reflects the highly regulated chronic response and potential lasting immunological consequences of dysbiosis in the microbiota. 25938477 4 78 theme significant 738:748 arg1 changes 750:756 significant changes 738:756 significant changes in α and β- diversity 738:778 Changes in microbial composition occurred between 14 and 28 days post infection, resulting in significant changes in α and β- diversity. 25938477 12 79 theme muris 1938:1942 arg1 infection 1922:1930 infection 1922:1930 infection of T. muris 1922:1942 Thus infection of T. muris causes a significant and substantial impact on intestinal microbiota and digestive function of mice with affects in long term immune regulation. 25938477 7 80 theme polysaccharides 1323:1337 arg1 digestion 1302:1310 the incomplete digestion 1287:1310 the incomplete digestion of dietary polysaccharides 1287:1337 The significant reduction in weight gain by infected mice probably reflects these metabolic changes and the incomplete digestion of dietary polysaccharides. 25938477 7 80 theme polysaccharides 1323:1337 arg1 changes 1275:1281 these metabolic changes 1259:1281 these metabolic changes 1259:1281 The significant reduction in weight gain by infected mice probably reflects these metabolic changes and the incomplete digestion of dietary polysaccharides. 25938477 11 81 from dysbiosis 1888:1896 arg1 microbiota 1905:1914 the microbiota 1901:1914 the microbiota 1901:1914 This reflects the highly regulated chronic response and potential lasting immunological consequences of dysbiosis in the microbiota. 25938477 0 82 theme Trichuris 8:16 arg1 muris 18:22 Trichuris muris 8:22 Chronic Trichuris muris Infection in C57BL/6 Mice 0:48 Chronic Trichuris muris Infection in C57BL/6 Mice Causes Significant Changes in Host Microbiota and Metabolome: Effects Reversed by Pathogen Clearance. 25938477 0 83 dep Host 80:83 arg1 Microbiota 85:94 Microbiota 85:94 Microbiota 85:94 Chronic Trichuris muris Infection in C57BL/6 Mice Causes Significant Changes in Host Microbiota and Metabolome: Effects Reversed by Pathogen Clearance. 25938477 6 84 from reduction 1120:1128 arg1 breakdown 1133:1141 breakdown 1133:1141 breakdown of dietary plant derived carbohydrates 1133:1180 Metabolomic analysis of stool samples of infected mice at day 41 showed significant differences to uninfected controls with a significant increase in the levels of a number of essential amino acids and a reduction in breakdown of dietary plant derived carbohydrates. 25938477 6 84 from reduction 1120:1128 arg1 levels 1070:1075 the levels 1066:1075 the levels of a number of essential amino acids 1066:1112 Metabolomic analysis of stool samples of infected mice at day 41 showed significant differences to uninfected controls with a significant increase in the levels of a number of essential amino acids and a reduction in breakdown of dietary plant derived carbohydrates. 25938477 2 85 theme first 352:356 arg1 investigation 399:411 the first ever highly controlled and comprehensive investigation 348:411 the first ever highly controlled and comprehensive investigation into the effects of T. muris infection on the faecal microbiota of mice and the effects on the microbiota following successful clearance of the infection 348:565 This paper describes the first ever highly controlled and comprehensive investigation into the effects of T. muris infection on the faecal microbiota of mice and the effects on the microbiota following successful clearance of the infection. 25938477 1 86 theme mouse 275:279 arg1 whipworm 281:288 mouse whipworm 275:288 mouse whipworm 275:288 Trichuris species are a globally important and prevalent group of intestinal helminth parasites, in which Trichuris muris (mouse whipworm) is an ideal model for this disease. 25938477 1 86 theme mouse 275:279 arg1 muris 268:272 Trichuris muris 258:272 Trichuris muris (mouse whipworm) 258:289 Trichuris species are a globally important and prevalent group of intestinal helminth parasites, in which Trichuris muris (mouse whipworm) is an ideal model for this disease. 25938477 0 87 dep Changes 69:75 arg1 Effects 112:118 Effects 112:118 Significant Changes in Host Microbiota and Metabolome: Effects Reversed by Pathogen Clearance 57:149 Chronic Trichuris muris Infection in C57BL/6 Mice Causes Significant Changes in Host Microbiota and Metabolome: Effects Reversed by Pathogen Clearance. 25938477 6 88 theme significant 1042:1052 arg1 increase 1054:1061 a significant increase 1040:1061 a significant increase in the levels of a number of essential amino acids 1040:1112 Metabolomic analysis of stool samples of infected mice at day 41 showed significant differences to uninfected controls with a significant increase in the levels of a number of essential amino acids and a reduction in breakdown of dietary plant derived carbohydrates. 25938477 0 89 theme C57BL/6 37:43 arg1 Mice 45:48 C57BL/6 Mice 37:48 C57BL/6 Mice 37:48 Chronic Trichuris muris Infection in C57BL/6 Mice Causes Significant Changes in Host Microbiota and Metabolome: Effects Reversed by Pathogen Clearance. 25938477 8 90 theme additional 1409:1418 arg1 changes 1420:1426 additional changes 1409:1426 additional changes gradually transitioning by day 91 towards a microbiota of an uninfected animal 1409:1505 Following clearance of infection the intestinal microbiota underwent additional changes gradually transitioning by day 91 towards a microbiota of an uninfected animal. 25938477 7 91 theme metabolic 1265:1273 arg1 changes 1275:1281 these metabolic changes 1259:1281 these metabolic changes 1259:1281 The significant reduction in weight gain by infected mice probably reflects these metabolic changes and the incomplete digestion of dietary polysaccharides. 25938477 2 92 theme muris 436:440 arg1 infection 442:450 T. muris infection 433:450 T. muris infection 433:450 This paper describes the first ever highly controlled and comprehensive investigation into the effects of T. muris infection on the faecal microbiota of mice and the effects on the microbiota following successful clearance of the infection. 25938477 5 93 dep diversity 829:837 arg1 the 825:827 the 825:827 the 825:827 This impact was dominated by a reduction in the diversity and abundance of Bacteroidetes, specifically Prevotella and Parabacteroides. 25938477 10 94 theme cell 1723:1726 arg1 populations 1728:1738 the key immune cell populations 1708:1738 the key immune cell populations associated with chronic T. muris infection 1708:1781 Interestingly this was not observed for all of the key immune cell populations associated with chronic T. muris infection. 25938477 6 95 theme amino 1102:1106 arg1 acids 1108:1112 essential amino acids 1092:1112 essential amino acids 1092:1112 Metabolomic analysis of stool samples of infected mice at day 41 showed significant differences to uninfected controls with a significant increase in the levels of a number of essential amino acids and a reduction in breakdown of dietary plant derived carbohydrates. 25938477 12 96 dep term 2065:2068 arg1 long 2060:2063 long 2060:2063 long 2060:2063 Thus infection of T. muris causes a significant and substantial impact on intestinal microbiota and digestive function of mice with affects in long term immune regulation. 25938477 10 97 theme key 1712:1714 arg1 populations 1728:1738 the key immune cell populations 1708:1738 the key immune cell populations associated with chronic T. muris infection 1708:1781 Interestingly this was not observed for all of the key immune cell populations associated with chronic T. muris infection. 25938477 1 98 theme helminth 229:236 arg1 parasites 238:246 intestinal helminth parasites 218:246 intestinal helminth parasites 218:246 Trichuris species are a globally important and prevalent group of intestinal helminth parasites, in which Trichuris muris (mouse whipworm) is an ideal model for this disease. 25938477 12 99 theme immune 2070:2075 arg1 regulation 2077:2086 long term immune regulation 2060:2086 long term immune regulation 2060:2086 Thus infection of T. muris causes a significant and substantial impact on intestinal microbiota and digestive function of mice with affects in long term immune regulation. 25938477 10 100 theme chronic 1756:1762 arg1 infection 1773:1781 chronic T. muris infection 1756:1781 chronic T. muris infection 1756:1781 Interestingly this was not observed for all of the key immune cell populations associated with chronic T. muris infection. 28493687 9 0 theme aromatic 971:978 arg1 1,2,4-benzenetriol 1018:1035 1,2,4-benzenetriol 1018:1035 1,2,4-benzenetriol 1018:1035 In addition, the levels of aromatic compounds (4-hydroxycinnamic acid and 1,2,4-benzenetriol) and their precursors (phenylalanine, tyrosine) were enhanced, indicating the activation of shikimate-phenylpropanoid biosynthesis in maize leaves, which is an antioxidant defense-related pathway. 28493687 9 0 theme aromatic 971:978 arg1 compounds 980:988 aromatic compounds 971:988 aromatic compounds (4-hydroxycinnamic acid and 1,2,4-benzenetriol) 971:1036 In addition, the levels of aromatic compounds (4-hydroxycinnamic acid and 1,2,4-benzenetriol) and their precursors (phenylalanine, tyrosine) were enhanced, indicating the activation of shikimate-phenylpropanoid biosynthesis in maize leaves, which is an antioxidant defense-related pathway. 28493687 9 0 theme aromatic 971:978 arg1 acid 1009:1012 4-hydroxycinnamic acid 991:1012 4-hydroxycinnamic acid 991:1012 In addition, the levels of aromatic compounds (4-hydroxycinnamic acid and 1,2,4-benzenetriol) and their precursors (phenylalanine, tyrosine) were enhanced, indicating the activation of shikimate-phenylpropanoid biosynthesis in maize leaves, which is an antioxidant defense-related pathway. 28493687 7 1 theme Cu 676:677 arg1 nanopesticide 684:696 the Cu(OH)2 nanopesticide 672:696 the Cu(OH)2 nanopesticide 672:696 Furthermore, the Cu(OH)2 nanopesticide induced metabolic reprogramming in both species, but in different manners. 28493687 7 2 theme different 754:762 arg1 manners 764:770 different manners 754:770 different manners 754:770 Furthermore, the Cu(OH)2 nanopesticide induced metabolic reprogramming in both species, but in different manners. 28493687 11 3 theme wall 1444:1447 arg1 composition 1449:1459 cell wall composition 1439:1459 cell wall composition 1439:1459 Both species exhibited altered levels of fatty acids and polysaccharides, suggesting the cell membrane and cell wall composition may change in response to Cu(OH)2 nanopesticide. 28493687 8 4 theme several 783:789 arg1 metabolites 804:814 several intermediate metabolites 783:814 several intermediate metabolites of the glycolysis pathway and tricarboxylic acid cycle (TCA) 783:875 In maize, several intermediate metabolites of the glycolysis pathway and tricarboxylic acid cycle (TCA) were up-regulated, indicating the energy metabolism was activated. 28493687 9 5 theme precursors 1048:1057 arg1 levels 961:966 the levels 957:966 the levels of aromatic compounds (4-hydroxycinnamic acid and 1,2,4-benzenetriol) and their precursors (phenylalanine, tyrosine) 957:1083 In addition, the levels of aromatic compounds (4-hydroxycinnamic acid and 1,2,4-benzenetriol) and their precursors (phenylalanine, tyrosine) were enhanced, indicating the activation of shikimate-phenylpropanoid biosynthesis in maize leaves, which is an antioxidant defense-related pathway. 28493687 11 6 theme Cu 1487:1488 arg1 nanopesticide 1495:1507 Cu(OH)2 nanopesticide 1487:1507 Cu(OH)2 nanopesticide 1487:1507 Both species exhibited altered levels of fatty acids and polysaccharides, suggesting the cell membrane and cell wall composition may change in response to Cu(OH)2 nanopesticide. 28493687 0 7 theme Zea 78:80 arg1 Corn 71:74 Corn 71:74 Corn ( Zea mays) 71:86 Comparative Metabolic Response between Cucumber ( Cucumis sativus) and Corn ( Zea mays) to a Cu(OH)2 Nanopesticide. 28493687 0 7 theme Zea 78:80 arg1 mays 82:85 Zea mays 78:85 Zea mays 78:85 Comparative Metabolic Response between Cucumber ( Cucumis sativus) and Corn ( Zea mays) to a Cu(OH)2 Nanopesticide. 28493687 9 8 dep maize 1171:1175 arg1 leaves 1177:1182 leaves 1177:1182 leaves 1177:1182 In addition, the levels of aromatic compounds (4-hydroxycinnamic acid and 1,2,4-benzenetriol) and their precursors (phenylalanine, tyrosine) were enhanced, indicating the activation of shikimate-phenylpropanoid biosynthesis in maize leaves, which is an antioxidant defense-related pathway. 28493687 12 9 theme plants 1591:1596 arg1 response 1573:1580 the differential response 1556:1580 the differential response of these plants to the same nanopesticide stressor 1556:1631 Thus, metabolomics helps to deeply understand the differential response of these plants to the same nanopesticide stressor. 28493687 9 10 theme 4-hydroxycinnamic 991:1007 arg1 compounds 980:988 aromatic compounds 971:988 aromatic compounds (4-hydroxycinnamic acid and 1,2,4-benzenetriol) 971:1036 In addition, the levels of aromatic compounds (4-hydroxycinnamic acid and 1,2,4-benzenetriol) and their precursors (phenylalanine, tyrosine) were enhanced, indicating the activation of shikimate-phenylpropanoid biosynthesis in maize leaves, which is an antioxidant defense-related pathway. 28493687 9 10 theme 4-hydroxycinnamic 991:1007 arg1 acid 1009:1012 4-hydroxycinnamic acid 991:1012 4-hydroxycinnamic acid 991:1012 In addition, the levels of aromatic compounds (4-hydroxycinnamic acid and 1,2,4-benzenetriol) and their precursors (phenylalanine, tyrosine) were enhanced, indicating the activation of shikimate-phenylpropanoid biosynthesis in maize leaves, which is an antioxidant defense-related pathway. 28493687 12 11 theme same 1605:1608 arg1 stressor 1624:1631 the same nanopesticide stressor 1601:1631 the same nanopesticide stressor 1601:1631 Thus, metabolomics helps to deeply understand the differential response of these plants to the same nanopesticide stressor. 28493687 5 12 theme species 551:557 arg1 responses 528:536 the metabolic responses 514:536 the metabolic responses of these two species 514:557 GC-TOF-MS-based metabolomics was employed to determine the metabolic responses of these two species. 28493687 8 13 theme energy 911:916 arg1 metabolism 918:927 the energy metabolism 907:927 the energy metabolism 907:927 In maize, several intermediate metabolites of the glycolysis pathway and tricarboxylic acid cycle (TCA) were up-regulated, indicating the energy metabolism was activated. 28493687 8 14 theme intermediate 791:802 arg1 metabolites 804:814 several intermediate metabolites 783:814 several intermediate metabolites of the glycolysis pathway and tricarboxylic acid cycle (TCA) 783:875 In maize, several intermediate metabolites of the glycolysis pathway and tricarboxylic acid cycle (TCA) were up-regulated, indicating the energy metabolism was activated. 28493687 9 15 theme shikimate-phenylpropanoid 1129:1153 arg1 biosynthesis 1155:1166 shikimate-phenylpropanoid biosynthesis 1129:1166 shikimate-phenylpropanoid biosynthesis 1129:1166 In addition, the levels of aromatic compounds (4-hydroxycinnamic acid and 1,2,4-benzenetriol) and their precursors (phenylalanine, tyrosine) were enhanced, indicating the activation of shikimate-phenylpropanoid biosynthesis in maize leaves, which is an antioxidant defense-related pathway. 28493687 12 16 theme nanopesticide 1610:1622 arg1 stressor 1624:1631 the same nanopesticide stressor 1601:1631 the same nanopesticide stressor 1601:1631 Thus, metabolomics helps to deeply understand the differential response of these plants to the same nanopesticide stressor. 28493687 0 17 theme Metabolic 12:20 arg1 Response 22:29 Comparative Metabolic Response 0:29 Comparative Metabolic Response between Cucumber ( Cucumis sativus) and Corn ( Zea mays) to a Cu(OH)2 Nanopesticide. 0:114 Comparative Metabolic Response between Cucumber ( Cucumis sativus) and Corn ( Zea mays) to a Cu(OH)2 Nanopesticide. 28493687 4 18 theme different 417:425 arg1 doses 427:431 different doses 417:431 different doses of Cu(OH)2 nanopesticide 417:456 We selected maize and cucumber as model plants for exposure to different doses of Cu(OH)2 nanopesticide. 28493687 9 19 theme biosynthesis 1155:1166 arg1 activation 1115:1124 the activation 1111:1124 the activation of shikimate-phenylpropanoid biosynthesis in maize leaves, which is an antioxidant defense-related pathway 1111:1231 In addition, the levels of aromatic compounds (4-hydroxycinnamic acid and 1,2,4-benzenetriol) and their precursors (phenylalanine, tyrosine) were enhanced, indicating the activation of shikimate-phenylpropanoid biosynthesis in maize leaves, which is an antioxidant defense-related pathway. 28493687 11 20 theme polysaccharides 1389:1403 arg1 levels 1363:1368 altered levels 1355:1368 altered levels of fatty acids and polysaccharides 1355:1403 Both species exhibited altered levels of fatty acids and polysaccharides, suggesting the cell membrane and cell wall composition may change in response to Cu(OH)2 nanopesticide. 28493687 0 21 theme Comparative 0:10 arg1 Response 22:29 Comparative Metabolic Response 0:29 Comparative Metabolic Response between Cucumber ( Cucumis sativus) and Corn ( Zea mays) to a Cu(OH)2 Nanopesticide. 0:114 Comparative Metabolic Response between Cucumber ( Cucumis sativus) and Corn ( Zea mays) to a Cu(OH)2 Nanopesticide. 28493687 8 22 theme pathway 834:840 arg1 metabolites 804:814 several intermediate metabolites 783:814 several intermediate metabolites of the glycolysis pathway and tricarboxylic acid cycle (TCA) 783:875 In maize, several intermediate metabolites of the glycolysis pathway and tricarboxylic acid cycle (TCA) were up-regulated, indicating the energy metabolism was activated. 28493687 1 23 theme unique 129:134 arg1 properties 136:145 their unique properties 123:145 their unique properties 123:145 Due to their unique properties, copper-based nanopesticides are emerging in the market. 28493687 3 24 theme cellular 310:317 arg1 responses 329:337 cellular metabolic responses 310:337 cellular metabolic responses to a stressor 310:351 Metabolomics can capture a snapshot of cellular metabolic responses to a stressor. 28493687 0 25 theme Cu 93:94 arg1 Nanopesticide 101:113 a Cu(OH)2 Nanopesticide 91:113 a Cu(OH)2 Nanopesticide 91:113 Comparative Metabolic Response between Cucumber ( Cucumis sativus) and Corn ( Zea mays) to a Cu(OH)2 Nanopesticide. 28493687 5 26 theme metabolic 518:526 arg1 responses 528:536 the metabolic responses 514:536 the metabolic responses of these two species 514:557 GC-TOF-MS-based metabolomics was employed to determine the metabolic responses of these two species. 28493687 8 27 theme glycolysis 823:832 arg1 pathway 834:840 the glycolysis pathway 819:840 the glycolysis pathway 819:840 In maize, several intermediate metabolites of the glycolysis pathway and tricarboxylic acid cycle (TCA) were up-regulated, indicating the energy metabolism was activated. 28493687 3 28 theme metabolic 319:327 arg1 responses 329:337 cellular metabolic responses 310:337 cellular metabolic responses to a stressor 310:351 Metabolomics can capture a snapshot of cellular metabolic responses to a stressor. 28493687 12 29 theme differential 1560:1571 arg1 response 1573:1580 the differential response 1556:1580 the differential response of these plants to the same nanopesticide stressor 1556:1631 Thus, metabolomics helps to deeply understand the differential response of these plants to the same nanopesticide stressor. 28493687 4 30 theme model 388:392 arg1 cucumber 376:383 cucumber 376:383 cucumber 376:383 We selected maize and cucumber as model plants for exposure to different doses of Cu(OH)2 nanopesticide. 28493687 4 30 theme model 388:392 arg1 plants 394:399 model plants 388:399 model plants 388:399 We selected maize and cucumber as model plants for exposure to different doses of Cu(OH)2 nanopesticide. 28493687 4 30 theme model 388:392 arg1 maize 366:370 maize 366:370 maize 366:370 We selected maize and cucumber as model plants for exposure to different doses of Cu(OH)2 nanopesticide. 28493687 2 31 theme crop 240:243 arg1 plants 245:250 crop plants 240:250 crop plants 240:250 Thus, understanding their effect on crop plants is very important. 28493687 8 32 theme tricarboxylic 846:858 arg1 TCA 872:874 TCA 872:874 TCA 872:874 In maize, several intermediate metabolites of the glycolysis pathway and tricarboxylic acid cycle (TCA) were up-regulated, indicating the energy metabolism was activated. 28493687 8 32 theme tricarboxylic 846:858 arg1 cycle 865:869 tricarboxylic acid cycle 846:869 tricarboxylic acid cycle (TCA) 846:875 In maize, several intermediate metabolites of the glycolysis pathway and tricarboxylic acid cycle (TCA) were up-regulated, indicating the energy metabolism was activated. 28493687 10 33 theme metabolic 1268:1276 arg1 pathways 1278:1285 arginine and proline metabolic pathways 1247:1285 arginine and proline metabolic pathways 1247:1285 In cucumber, arginine and proline metabolic pathways were the most significantly altered pathway. 28493687 10 33 theme metabolic 1268:1276 arg1 pathway 1323:1329 the most significantly altered pathway 1292:1329 the most significantly altered pathway 1292:1329 In cucumber, arginine and proline metabolic pathways were the most significantly altered pathway. 28493687 11 34 theme cell 1421:1424 arg1 membrane 1426:1433 the cell membrane 1417:1433 the cell membrane 1417:1433 Both species exhibited altered levels of fatty acids and polysaccharides, suggesting the cell membrane and cell wall composition may change in response to Cu(OH)2 nanopesticide. 28493687 0 35 theme OH 96:97 arg1 Nanopesticide 101:113 a Cu(OH)2 Nanopesticide 91:113 a Cu(OH)2 Nanopesticide 91:113 Comparative Metabolic Response between Cucumber ( Cucumis sativus) and Corn ( Zea mays) to a Cu(OH)2 Nanopesticide. 28493687 9 36 theme compounds 980:988 arg1 levels 961:966 the levels 957:966 the levels of aromatic compounds (4-hydroxycinnamic acid and 1,2,4-benzenetriol) and their precursors (phenylalanine, tyrosine) 957:1083 In addition, the levels of aromatic compounds (4-hydroxycinnamic acid and 1,2,4-benzenetriol) and their precursors (phenylalanine, tyrosine) were enhanced, indicating the activation of shikimate-phenylpropanoid biosynthesis in maize leaves, which is an antioxidant defense-related pathway. 28493687 6 37 from differences 589:599 arg1 changes 623:629 metabolite profile changes 604:629 metabolite profile changes 604:629 Results revealed significant differences in metabolite profile changes between maize and cucumber. 28493687 6 38 theme profile 615:621 arg1 changes 623:629 metabolite profile changes 604:629 metabolite profile changes 604:629 Results revealed significant differences in metabolite profile changes between maize and cucumber. 28493687 1 39 theme copper-based 148:159 arg1 nanopesticides 161:174 copper-based nanopesticides 148:174 copper-based nanopesticides 148:174 Due to their unique properties, copper-based nanopesticides are emerging in the market. 28493687 4 40 theme 2 442:442 arg1 nanopesticide 444:456 nanopesticide 444:456 nanopesticide 444:456 We selected maize and cucumber as model plants for exposure to different doses of Cu(OH)2 nanopesticide. 28493687 5 41 theme GC-TOF-MS-based 459:473 arg1 metabolomics 475:486 GC-TOF-MS-based metabolomics 459:486 GC-TOF-MS-based metabolomics 459:486 GC-TOF-MS-based metabolomics was employed to determine the metabolic responses of these two species. 28493687 7 42 theme metabolic 706:714 arg1 reprogramming 716:728 metabolic reprogramming 706:728 metabolic reprogramming 706:728 Furthermore, the Cu(OH)2 nanopesticide induced metabolic reprogramming in both species, but in different manners. 28493687 11 43 theme fatty 1373:1377 arg1 acids 1379:1383 fatty acids 1373:1383 fatty acids 1373:1383 Both species exhibited altered levels of fatty acids and polysaccharides, suggesting the cell membrane and cell wall composition may change in response to Cu(OH)2 nanopesticide. 28493687 10 44 theme arginine 1247:1254 arg1 pathways 1278:1285 arginine and proline metabolic pathways 1247:1285 arginine and proline metabolic pathways 1247:1285 In cucumber, arginine and proline metabolic pathways were the most significantly altered pathway. 28493687 10 44 theme arginine 1247:1254 arg1 pathway 1323:1329 the most significantly altered pathway 1292:1329 the most significantly altered pathway 1292:1329 In cucumber, arginine and proline metabolic pathways were the most significantly altered pathway. 28493687 8 45 theme acid 860:863 arg1 TCA 872:874 TCA 872:874 TCA 872:874 In maize, several intermediate metabolites of the glycolysis pathway and tricarboxylic acid cycle (TCA) were up-regulated, indicating the energy metabolism was activated. 28493687 8 45 theme acid 860:863 arg1 cycle 865:869 tricarboxylic acid cycle 846:869 tricarboxylic acid cycle (TCA) 846:875 In maize, several intermediate metabolites of the glycolysis pathway and tricarboxylic acid cycle (TCA) were up-regulated, indicating the energy metabolism was activated. 28493687 0 46 theme Cucumis 50:56 arg1 Cucumber 39:46 Cucumber 39:46 Cucumber ( Cucumis sativus) 39:65 Comparative Metabolic Response between Cucumber ( Cucumis sativus) and Corn ( Zea mays) to a Cu(OH)2 Nanopesticide. 28493687 0 46 theme Cucumis 50:56 arg1 sativus 58:64 Cucumis sativus 50:64 Cucumis sativus 50:64 Comparative Metabolic Response between Cucumber ( Cucumis sativus) and Corn ( Zea mays) to a Cu(OH)2 Nanopesticide. 28493687 11 47 dep nanopesticide 1495:1507 arg1 response 1475:1482 response 1475:1482 response 1475:1482 Both species exhibited altered levels of fatty acids and polysaccharides, suggesting the cell membrane and cell wall composition may change in response to Cu(OH)2 nanopesticide. 28493687 6 48 theme metabolite 604:613 arg1 changes 623:629 metabolite profile changes 604:629 metabolite profile changes 604:629 Results revealed significant differences in metabolite profile changes between maize and cucumber. 28493687 4 49 theme nanopesticide 444:456 arg1 Cu 436:437 Cu 436:437 Cu(OH)2 nanopesticide 436:456 We selected maize and cucumber as model plants for exposure to different doses of Cu(OH)2 nanopesticide. 28493687 4 49 theme nanopesticide 444:456 arg1 OH 439:440 OH 439:440 OH 439:440 We selected maize and cucumber as model plants for exposure to different doses of Cu(OH)2 nanopesticide. 28493687 9 50 theme antioxidant 1197:1207 arg1 maize 1171:1175 maize leaves 1171:1182 maize leaves 1171:1182 In addition, the levels of aromatic compounds (4-hydroxycinnamic acid and 1,2,4-benzenetriol) and their precursors (phenylalanine, tyrosine) were enhanced, indicating the activation of shikimate-phenylpropanoid biosynthesis in maize leaves, which is an antioxidant defense-related pathway. 28493687 9 50 theme antioxidant 1197:1207 arg1 pathway 1225:1231 an antioxidant defense-related pathway 1194:1231 an antioxidant defense-related pathway 1194:1231 In addition, the levels of aromatic compounds (4-hydroxycinnamic acid and 1,2,4-benzenetriol) and their precursors (phenylalanine, tyrosine) were enhanced, indicating the activation of shikimate-phenylpropanoid biosynthesis in maize leaves, which is an antioxidant defense-related pathway. 28493687 10 51 from pathway 1323:1329 arg1 cucumber 1237:1244 cucumber 1237:1244 cucumber 1237:1244 In cucumber, arginine and proline metabolic pathways were the most significantly altered pathway. 28493687 9 52 theme defense-related 1209:1223 arg1 maize 1171:1175 maize leaves 1171:1182 maize leaves 1171:1182 In addition, the levels of aromatic compounds (4-hydroxycinnamic acid and 1,2,4-benzenetriol) and their precursors (phenylalanine, tyrosine) were enhanced, indicating the activation of shikimate-phenylpropanoid biosynthesis in maize leaves, which is an antioxidant defense-related pathway. 28493687 9 52 theme defense-related 1209:1223 arg1 pathway 1225:1231 an antioxidant defense-related pathway 1194:1231 an antioxidant defense-related pathway 1194:1231 In addition, the levels of aromatic compounds (4-hydroxycinnamic acid and 1,2,4-benzenetriol) and their precursors (phenylalanine, tyrosine) were enhanced, indicating the activation of shikimate-phenylpropanoid biosynthesis in maize leaves, which is an antioxidant defense-related pathway. 28493687 8 53 theme cycle 865:869 arg1 metabolites 804:814 several intermediate metabolites 783:814 several intermediate metabolites of the glycolysis pathway and tricarboxylic acid cycle (TCA) 783:875 In maize, several intermediate metabolites of the glycolysis pathway and tricarboxylic acid cycle (TCA) were up-regulated, indicating the energy metabolism was activated. 28493687 10 54 theme proline 1260:1266 arg1 pathways 1278:1285 arginine and proline metabolic pathways 1247:1285 arginine and proline metabolic pathways 1247:1285 In cucumber, arginine and proline metabolic pathways were the most significantly altered pathway. 28493687 10 54 theme proline 1260:1266 arg1 pathway 1323:1329 the most significantly altered pathway 1292:1329 the most significantly altered pathway 1292:1329 In cucumber, arginine and proline metabolic pathways were the most significantly altered pathway. 28493687 11 55 theme cell 1439:1442 arg1 composition 1449:1459 cell wall composition 1439:1459 cell wall composition 1439:1459 Both species exhibited altered levels of fatty acids and polysaccharides, suggesting the cell membrane and cell wall composition may change in response to Cu(OH)2 nanopesticide. 28493687 9 56 dep compounds 980:988 arg1 1,2,4-benzenetriol 1018:1035 1,2,4-benzenetriol 1018:1035 1,2,4-benzenetriol 1018:1035 In addition, the levels of aromatic compounds (4-hydroxycinnamic acid and 1,2,4-benzenetriol) and their precursors (phenylalanine, tyrosine) were enhanced, indicating the activation of shikimate-phenylpropanoid biosynthesis in maize leaves, which is an antioxidant defense-related pathway. 28493687 9 56 dep compounds 980:988 arg1 compounds 980:988 aromatic compounds 971:988 aromatic compounds (4-hydroxycinnamic acid and 1,2,4-benzenetriol) 971:1036 In addition, the levels of aromatic compounds (4-hydroxycinnamic acid and 1,2,4-benzenetriol) and their precursors (phenylalanine, tyrosine) were enhanced, indicating the activation of shikimate-phenylpropanoid biosynthesis in maize leaves, which is an antioxidant defense-related pathway. 28493687 9 56 dep compounds 980:988 arg1 acid 1009:1012 4-hydroxycinnamic acid 991:1012 4-hydroxycinnamic acid 991:1012 In addition, the levels of aromatic compounds (4-hydroxycinnamic acid and 1,2,4-benzenetriol) and their precursors (phenylalanine, tyrosine) were enhanced, indicating the activation of shikimate-phenylpropanoid biosynthesis in maize leaves, which is an antioxidant defense-related pathway. 28493687 9 57 dep precursors 1048:1057 arg1 tyrosine 1075:1082 tyrosine 1075:1082 tyrosine 1075:1082 In addition, the levels of aromatic compounds (4-hydroxycinnamic acid and 1,2,4-benzenetriol) and their precursors (phenylalanine, tyrosine) were enhanced, indicating the activation of shikimate-phenylpropanoid biosynthesis in maize leaves, which is an antioxidant defense-related pathway. 28493687 9 57 dep precursors 1048:1057 arg1 phenylalanine 1060:1072 phenylalanine 1060:1072 phenylalanine 1060:1072 In addition, the levels of aromatic compounds (4-hydroxycinnamic acid and 1,2,4-benzenetriol) and their precursors (phenylalanine, tyrosine) were enhanced, indicating the activation of shikimate-phenylpropanoid biosynthesis in maize leaves, which is an antioxidant defense-related pathway. 28493687 9 58 from activation 1115:1124 arg1 pathway 1225:1231 an antioxidant defense-related pathway 1194:1231 an antioxidant defense-related pathway 1194:1231 In addition, the levels of aromatic compounds (4-hydroxycinnamic acid and 1,2,4-benzenetriol) and their precursors (phenylalanine, tyrosine) were enhanced, indicating the activation of shikimate-phenylpropanoid biosynthesis in maize leaves, which is an antioxidant defense-related pathway. 28493687 9 58 from activation 1115:1124 arg1 maize 1171:1175 maize leaves 1171:1182 maize leaves 1171:1182 In addition, the levels of aromatic compounds (4-hydroxycinnamic acid and 1,2,4-benzenetriol) and their precursors (phenylalanine, tyrosine) were enhanced, indicating the activation of shikimate-phenylpropanoid biosynthesis in maize leaves, which is an antioxidant defense-related pathway. 28493687 2 59 from effect 230:235 arg1 plants 245:250 crop plants 240:250 crop plants 240:250 Thus, understanding their effect on crop plants is very important. 28493687 7 60 theme OH 679:680 arg1 nanopesticide 684:696 the Cu(OH)2 nanopesticide 672:696 the Cu(OH)2 nanopesticide 672:696 Furthermore, the Cu(OH)2 nanopesticide induced metabolic reprogramming in both species, but in different manners. 28493687 11 61 theme altered 1355:1361 arg1 levels 1363:1368 altered levels 1355:1368 altered levels of fatty acids and polysaccharides 1355:1403 Both species exhibited altered levels of fatty acids and polysaccharides, suggesting the cell membrane and cell wall composition may change in response to Cu(OH)2 nanopesticide. 28493687 4 62 theme Cu 436:437 arg1 doses 427:431 different doses 417:431 different doses of Cu(OH)2 nanopesticide 417:456 We selected maize and cucumber as model plants for exposure to different doses of Cu(OH)2 nanopesticide. 28493687 6 63 theme significant 577:587 arg1 differences 589:599 significant differences 577:599 significant differences in metabolite profile changes between maize and cucumber 577:656 Results revealed significant differences in metabolite profile changes between maize and cucumber. 28493687 10 64 theme altered 1315:1321 arg1 pathways 1278:1285 arginine and proline metabolic pathways 1247:1285 arginine and proline metabolic pathways 1247:1285 In cucumber, arginine and proline metabolic pathways were the most significantly altered pathway. 28493687 10 64 theme altered 1315:1321 arg1 pathway 1323:1329 the most significantly altered pathway 1292:1329 the most significantly altered pathway 1292:1329 In cucumber, arginine and proline metabolic pathways were the most significantly altered pathway. 28493687 3 65 theme responses 329:337 arg1 snapshot 298:305 a snapshot 296:305 a snapshot of cellular metabolic responses to a stressor 296:351 Metabolomics can capture a snapshot of cellular metabolic responses to a stressor. 28493687 11 66 theme acids 1379:1383 arg1 levels 1363:1368 altered levels 1355:1368 altered levels of fatty acids and polysaccharides 1355:1403 Both species exhibited altered levels of fatty acids and polysaccharides, suggesting the cell membrane and cell wall composition may change in response to Cu(OH)2 nanopesticide. 28276612 5 0 located observed 936:943 arg1 groups 965:970 the LIT and HIIT groups 948:970 the LIT and HIIT groups 948:970 No significant differences in microbiota were apparent between activity conditions in rats fed a HF diet but changes in the presence/absence of phylotypes were observed in the LIT and HIIT groups. 28276612 5 0 located observed 936:943 arg2 changes 885:891 changes 885:891 changes in the presence/absence of phylotypes 885:929 No significant differences in microbiota were apparent between activity conditions in rats fed a HF diet but changes in the presence/absence of phylotypes were observed in the LIT and HIIT groups. 28276612 4 1 theme interval 582:589 arg1 control 661:667 sedentary and normal control 640:667 sedentary and normal control 640:667 METHODS AND RESULTS A rat model was used to examine the intestinal microbiota responses to four activity conditions, including: high-intensity interval training (HIIT), light-intensity training (LIT), sedentary and normal control, each containing two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet. 28276612 4 1 theme interval 582:589 arg1 training 624:631 light-intensity training 608:631 light-intensity training (LIT) 608:637 METHODS AND RESULTS A rat model was used to examine the intestinal microbiota responses to four activity conditions, including: high-intensity interval training (HIIT), light-intensity training (LIT), sedentary and normal control, each containing two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet. 28276612 4 1 theme interval 582:589 arg1 HIIT 601:604 HIIT 601:604 HIIT 601:604 METHODS AND RESULTS A rat model was used to examine the intestinal microbiota responses to four activity conditions, including: high-intensity interval training (HIIT), light-intensity training (LIT), sedentary and normal control, each containing two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet. 28276612 4 1 theme interval 582:589 arg1 each 670:673 each 670:673 each 670:673 METHODS AND RESULTS A rat model was used to examine the intestinal microbiota responses to four activity conditions, including: high-intensity interval training (HIIT), light-intensity training (LIT), sedentary and normal control, each containing two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet. 28276612 4 1 theme interval 582:589 arg1 training 591:598 high-intensity interval training 567:598 high-intensity interval training (HIIT) 567:605 METHODS AND RESULTS A rat model was used to examine the intestinal microbiota responses to four activity conditions, including: high-intensity interval training (HIIT), light-intensity training (LIT), sedentary and normal control, each containing two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet. 28276612 2 2 theme exercise 278:285 arg1 behaviours 287:296 nutritional and exercise behaviours 262:296 nutritional and exercise behaviours 262:296 Many of these conditions are influenced by nutritional and exercise behaviours. 28276612 9 3 dep rats 1544:1547 arg1 showed 1560:1565 showed 1560:1565 showed little response 1560:1581 CONCLUSIONS While a significant effect of exercise on microbiota composition occurred in SC-fed rats, the HF-fed rats microbiota showed little response. 28276612 6 4 from rats 976:979 arg1 evident 1043:1049 evident 1043:1049 evident 1043:1049 In rats fed SC, significant differences in intestinal microbiota were evident between exercised and nonexercised rats. 28276612 2 5 theme nutritional 262:272 arg1 behaviours 287:296 nutritional and exercise behaviours 262:296 nutritional and exercise behaviours 262:296 Many of these conditions are influenced by nutritional and exercise behaviours. 28276612 8 6 from increase 1385:1392 arg1 bacteria 1315:1322 bacteria 1315:1322 bacteria likely capable of degrading resistant polysaccharides 1315:1376 Characterization of the exercise-induced bacterial phylotypes indicated an increase in bacteria likely capable of degrading resistant polysaccharides and an increase in short chain fatty acid producers. 28276612 8 6 from increase 1385:1392 arg1 producers 1420:1428 short chain fatty acid producers 1397:1428 short chain fatty acid producers 1397:1428 Characterization of the exercise-induced bacterial phylotypes indicated an increase in bacteria likely capable of degrading resistant polysaccharides and an increase in short chain fatty acid producers. 28276612 1 7 theme conditions 165:174 arg1 development 141:151 the development 137:151 the development of clinical conditions, including metabolic syndrome and obesity 137:216 AIMS Intestinal microbiota modulates the development of clinical conditions, including metabolic syndrome and obesity. 28276612 4 8 theme sedentary 640:648 arg1 control 661:667 sedentary and normal control 640:667 sedentary and normal control 640:667 METHODS AND RESULTS A rat model was used to examine the intestinal microbiota responses to four activity conditions, including: high-intensity interval training (HIIT), light-intensity training (LIT), sedentary and normal control, each containing two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet. 28276612 4 8 theme sedentary 640:648 arg1 training 591:598 high-intensity interval training 567:598 high-intensity interval training (HIIT) 567:605 METHODS AND RESULTS A rat model was used to examine the intestinal microbiota responses to four activity conditions, including: high-intensity interval training (HIIT), light-intensity training (LIT), sedentary and normal control, each containing two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet. 28276612 4 9 theme light-intensity 608:622 arg1 training 624:631 light-intensity training 608:631 light-intensity training (LIT) 608:637 METHODS AND RESULTS A rat model was used to examine the intestinal microbiota responses to four activity conditions, including: high-intensity interval training (HIIT), light-intensity training (LIT), sedentary and normal control, each containing two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet. 28276612 4 9 theme light-intensity 608:622 arg1 training 591:598 high-intensity interval training 567:598 high-intensity interval training (HIIT) 567:605 METHODS AND RESULTS A rat model was used to examine the intestinal microbiota responses to four activity conditions, including: high-intensity interval training (HIIT), light-intensity training (LIT), sedentary and normal control, each containing two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet. 28276612 4 9 theme light-intensity 608:622 arg1 LIT 634:636 LIT 634:636 LIT 634:636 METHODS AND RESULTS A rat model was used to examine the intestinal microbiota responses to four activity conditions, including: high-intensity interval training (HIIT), light-intensity training (LIT), sedentary and normal control, each containing two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet. 28276612 11 10 theme intestinal 1789:1798 arg1 bacteria 1800:1807 intestinal bacteria 1789:1807 intestinal bacteria 1789:1807 SIGNIFICANCE AND IMPACT OF THE STUDY The importance of diet-exercise interaction is extended to the level of intestinal bacteria and gut health. 28276612 5 11 theme significant 779:789 arg1 differences 791:801 No significant differences 776:801 No significant differences in microbiota 776:815 No significant differences in microbiota were apparent between activity conditions in rats fed a HF diet but changes in the presence/absence of phylotypes were observed in the LIT and HIIT groups. 28276612 1 12 theme AIMS 100:103 arg1 microbiota 116:125 AIMS Intestinal microbiota 100:125 AIMS Intestinal microbiota 100:125 AIMS Intestinal microbiota modulates the development of clinical conditions, including metabolic syndrome and obesity. 28276612 5 13 from differences 791:801 arg1 microbiota 806:815 microbiota 806:815 microbiota 806:815 No significant differences in microbiota were apparent between activity conditions in rats fed a HF diet but changes in the presence/absence of phylotypes were observed in the LIT and HIIT groups. 28276612 9 14 theme exercise 1473:1480 arg1 effect 1463:1468 a significant effect 1449:1468 a significant effect of exercise on microbiota composition 1449:1506 CONCLUSIONS While a significant effect of exercise on microbiota composition occurred in SC-fed rats, the HF-fed rats microbiota showed little response. 28276612 8 15 theme exercise-induced 1252:1267 arg1 phylotypes 1279:1288 the exercise-induced bacterial phylotypes 1248:1288 the exercise-induced bacterial phylotypes 1248:1288 Characterization of the exercise-induced bacterial phylotypes indicated an increase in bacteria likely capable of degrading resistant polysaccharides and an increase in short chain fatty acid producers. 28276612 11 16 theme health 1817:1822 arg1 level 1780:1784 the level 1776:1784 the level of intestinal bacteria and gut health 1776:1822 SIGNIFICANCE AND IMPACT OF THE STUDY The importance of diet-exercise interaction is extended to the level of intestinal bacteria and gut health. 28276612 9 17 theme microbiota 1485:1494 arg1 composition 1496:1506 microbiota composition 1485:1506 microbiota composition 1485:1506 CONCLUSIONS While a significant effect of exercise on microbiota composition occurred in SC-fed rats, the HF-fed rats microbiota showed little response. 28276612 8 18 theme phylotypes 1279:1288 arg1 Characterization 1228:1243 Characterization 1228:1243 Characterization of the exercise-induced bacterial phylotypes 1228:1288 Characterization of the exercise-induced bacterial phylotypes indicated an increase in bacteria likely capable of degrading resistant polysaccharides and an increase in short chain fatty acid producers. 28276612 5 19 from apparent 822:829 arg1 rats 862:865 rats 862:865 rats fed a HF diet 862:879 No significant differences in microbiota were apparent between activity conditions in rats fed a HF diet but changes in the presence/absence of phylotypes were observed in the LIT and HIIT groups. 28276612 4 20 dep conditions 702:711 arg1 HF 743:744 HF 743:744 HF 743:744 METHODS AND RESULTS A rat model was used to examine the intestinal microbiota responses to four activity conditions, including: high-intensity interval training (HIIT), light-intensity training (LIT), sedentary and normal control, each containing two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet. 28276612 4 20 dep conditions 702:711 arg1 conditions 702:711 two nutritional conditions 686:711 two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet 686:773 METHODS AND RESULTS A rat model was used to examine the intestinal microbiota responses to four activity conditions, including: high-intensity interval training (HIIT), light-intensity training (LIT), sedentary and normal control, each containing two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet. 28276612 4 20 dep conditions 702:711 arg1 diet 770:773 standard chow (SC) diet 751:773 standard chow (SC) diet 751:773 METHODS AND RESULTS A rat model was used to examine the intestinal microbiota responses to four activity conditions, including: high-intensity interval training (HIIT), light-intensity training (LIT), sedentary and normal control, each containing two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet. 28276612 4 20 dep conditions 702:711 arg1 diet 737:740 high-fat high-fructose diet 714:740 high-fat high-fructose diet (HF) 714:745 METHODS AND RESULTS A rat model was used to examine the intestinal microbiota responses to four activity conditions, including: high-intensity interval training (HIIT), light-intensity training (LIT), sedentary and normal control, each containing two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet. 28276612 5 21 theme HF 873:874 arg1 diet 876:879 a HF diet 871:879 a HF diet 871:879 No significant differences in microbiota were apparent between activity conditions in rats fed a HF diet but changes in the presence/absence of phylotypes were observed in the LIT and HIIT groups. 28276612 4 22 theme normal 654:659 arg1 control 661:667 sedentary and normal control 640:667 sedentary and normal control 640:667 METHODS AND RESULTS A rat model was used to examine the intestinal microbiota responses to four activity conditions, including: high-intensity interval training (HIIT), light-intensity training (LIT), sedentary and normal control, each containing two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet. 28276612 4 22 theme normal 654:659 arg1 training 591:598 high-intensity interval training 567:598 high-intensity interval training (HIIT) 567:605 METHODS AND RESULTS A rat model was used to examine the intestinal microbiota responses to four activity conditions, including: high-intensity interval training (HIIT), light-intensity training (LIT), sedentary and normal control, each containing two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet. 28276612 11 23 theme diet-exercise 1735:1747 arg1 interaction 1749:1759 diet-exercise interaction 1735:1759 diet-exercise interaction 1735:1759 SIGNIFICANCE AND IMPACT OF THE STUDY The importance of diet-exercise interaction is extended to the level of intestinal bacteria and gut health. 28276612 0 24 theme exercise 42:49 arg1 influence 29:37 the combined influence 16:37 the combined influence of exercise and diet on gastrointestinal microbiota in rats 16:97 A gut reaction: the combined influence of exercise and diet on gastrointestinal microbiota in rats. 28276612 2 25 theme conditions 233:242 arg1 Many 219:222 Many 219:222 Many 219:222 Many of these conditions are influenced by nutritional and exercise behaviours. 28276612 2 25 theme conditions 233:242 arg1 conditions 233:242 these conditions 227:242 these conditions 227:242 Many of these conditions are influenced by nutritional and exercise behaviours. 28276612 9 26 theme SC-fed 1520:1525 arg1 rats 1527:1530 SC-fed rats 1520:1530 SC-fed rats 1520:1530 CONCLUSIONS While a significant effect of exercise on microbiota composition occurred in SC-fed rats, the HF-fed rats microbiota showed little response. 28276612 0 27 theme diet 55:58 arg1 influence 29:37 the combined influence 16:37 the combined influence of exercise and diet on gastrointestinal microbiota in rats 16:97 A gut reaction: the combined influence of exercise and diet on gastrointestinal microbiota in rats. 28276612 0 28 theme gastrointestinal 63:78 arg1 microbiota 80:89 gastrointestinal microbiota 63:89 gastrointestinal microbiota in rats 63:97 A gut reaction: the combined influence of exercise and diet on gastrointestinal microbiota in rats. 28276612 4 29 theme nutritional 690:700 arg1 conditions 702:711 two nutritional conditions 686:711 two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet 686:773 METHODS AND RESULTS A rat model was used to examine the intestinal microbiota responses to four activity conditions, including: high-intensity interval training (HIIT), light-intensity training (LIT), sedentary and normal control, each containing two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet. 28276612 4 29 theme nutritional 690:700 arg1 diet 770:773 standard chow (SC) diet 751:773 standard chow (SC) diet 751:773 METHODS AND RESULTS A rat model was used to examine the intestinal microbiota responses to four activity conditions, including: high-intensity interval training (HIIT), light-intensity training (LIT), sedentary and normal control, each containing two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet. 28276612 4 29 theme nutritional 690:700 arg1 diet 737:740 high-fat high-fructose diet 714:740 high-fat high-fructose diet (HF) 714:745 METHODS AND RESULTS A rat model was used to examine the intestinal microbiota responses to four activity conditions, including: high-intensity interval training (HIIT), light-intensity training (LIT), sedentary and normal control, each containing two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet. 28276612 0 30 from influence 29:37 arg1 microbiota 80:89 gastrointestinal microbiota 63:89 gastrointestinal microbiota in rats 63:97 A gut reaction: the combined influence of exercise and diet on gastrointestinal microbiota in rats. 28276612 3 31 from microbiota 382:391 arg1 process 430:436 the process 426:436 the process 426:436 This study aimed to investigate the ability of exercise to re-shape the intestinal microbiota and the influence of the diet on the process. 28276612 8 32 theme resistant 1352:1360 arg1 polysaccharides 1362:1376 resistant polysaccharides 1352:1376 resistant polysaccharides 1352:1376 Characterization of the exercise-induced bacterial phylotypes indicated an increase in bacteria likely capable of degrading resistant polysaccharides and an increase in short chain fatty acid producers. 28276612 3 33 theme diet 418:421 arg1 microbiota 382:391 the intestinal microbiota 367:391 the intestinal microbiota 367:391 This study aimed to investigate the ability of exercise to re-shape the intestinal microbiota and the influence of the diet on the process. 28276612 3 33 theme diet 418:421 arg1 influence 401:409 the influence 397:409 the influence of the diet on the process 397:436 This study aimed to investigate the ability of exercise to re-shape the intestinal microbiota and the influence of the diet on the process. 28276612 7 34 theme significant 1118:1128 arg1 differences 1130:1140 significant differences 1118:1140 significant differences in intestinal microbiota in SC-fed rats 1118:1180 Both LIT and HIIT induced significant differences in intestinal microbiota in SC-fed rats compared to their respective SC-fed controls. 28276612 9 35 theme little 1567:1572 arg1 response 1574:1581 little response 1567:1581 little response 1567:1581 CONCLUSIONS While a significant effect of exercise on microbiota composition occurred in SC-fed rats, the HF-fed rats microbiota showed little response. 28276612 4 36 theme high-fructose 723:735 arg1 conditions 702:711 two nutritional conditions 686:711 two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet 686:773 METHODS AND RESULTS A rat model was used to examine the intestinal microbiota responses to four activity conditions, including: high-intensity interval training (HIIT), light-intensity training (LIT), sedentary and normal control, each containing two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet. 28276612 4 36 theme high-fructose 723:735 arg1 HF 743:744 HF 743:744 HF 743:744 METHODS AND RESULTS A rat model was used to examine the intestinal microbiota responses to four activity conditions, including: high-intensity interval training (HIIT), light-intensity training (LIT), sedentary and normal control, each containing two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet. 28276612 4 36 theme high-fructose 723:735 arg1 diet 737:740 high-fat high-fructose diet 714:740 high-fat high-fructose diet (HF) 714:745 METHODS AND RESULTS A rat model was used to examine the intestinal microbiota responses to four activity conditions, including: high-intensity interval training (HIIT), light-intensity training (LIT), sedentary and normal control, each containing two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet. 28276612 0 37 dep influence 29:37 arg1 reaction 6:13 A gut reaction 0:13 A gut reaction 0:13 A gut reaction: the combined influence of exercise and diet on gastrointestinal microbiota in rats. 28276612 4 38 theme intestinal 495:504 arg1 responses 517:525 the intestinal microbiota responses 491:525 the intestinal microbiota responses to four activity conditions, including: high-intensity interval training (HIIT), light-intensity training (LIT), sedentary and normal control, each containing two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet 491:773 METHODS AND RESULTS A rat model was used to examine the intestinal microbiota responses to four activity conditions, including: high-intensity interval training (HIIT), light-intensity training (LIT), sedentary and normal control, each containing two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet. 28276612 8 39 theme short 1397:1401 arg1 producers 1420:1428 short chain fatty acid producers 1397:1428 short chain fatty acid producers 1397:1428 Characterization of the exercise-induced bacterial phylotypes indicated an increase in bacteria likely capable of degrading resistant polysaccharides and an increase in short chain fatty acid producers. 28276612 8 40 theme fatty 1409:1413 arg1 producers 1420:1428 short chain fatty acid producers 1397:1428 short chain fatty acid producers 1397:1428 Characterization of the exercise-induced bacterial phylotypes indicated an increase in bacteria likely capable of degrading resistant polysaccharides and an increase in short chain fatty acid producers. 28276612 5 41 theme HIIT 960:963 arg1 groups 965:970 the LIT and HIIT groups 948:970 the LIT and HIIT groups 948:970 No significant differences in microbiota were apparent between activity conditions in rats fed a HF diet but changes in the presence/absence of phylotypes were observed in the LIT and HIIT groups. 28276612 5 42 from changes 885:891 arg1 presence/absence 900:915 the presence/absence 896:915 the presence/absence of phylotypes 896:929 No significant differences in microbiota were apparent between activity conditions in rats fed a HF diet but changes in the presence/absence of phylotypes were observed in the LIT and HIIT groups. 28276612 5 43 theme LIT 952:954 arg1 groups 965:970 the LIT and HIIT groups 948:970 the LIT and HIIT groups 948:970 No significant differences in microbiota were apparent between activity conditions in rats fed a HF diet but changes in the presence/absence of phylotypes were observed in the LIT and HIIT groups. 28276612 7 44 theme SC-fed 1211:1216 arg1 controls 1218:1225 their respective SC-fed controls 1194:1225 their respective SC-fed controls 1194:1225 Both LIT and HIIT induced significant differences in intestinal microbiota in SC-fed rats compared to their respective SC-fed controls. 28276612 6 45 theme intestinal 1016:1025 arg1 microbiota 1027:1036 intestinal microbiota 1016:1036 intestinal microbiota 1016:1036 In rats fed SC, significant differences in intestinal microbiota were evident between exercised and nonexercised rats. 28276612 4 46 dep METHODS 439:445 arg1 used 475:478 used 475:478 was used to examine the intestinal microbiota responses to four activity conditions, including: high-intensity interval training (HIIT), light-intensity training (LIT), sedentary and normal control, each containing two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet 471:773 METHODS AND RESULTS A rat model was used to examine the intestinal microbiota responses to four activity conditions, including: high-intensity interval training (HIIT), light-intensity training (LIT), sedentary and normal control, each containing two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet. 28276612 4 47 theme high-intensity 567:580 arg1 control 661:667 sedentary and normal control 640:667 sedentary and normal control 640:667 METHODS AND RESULTS A rat model was used to examine the intestinal microbiota responses to four activity conditions, including: high-intensity interval training (HIIT), light-intensity training (LIT), sedentary and normal control, each containing two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet. 28276612 4 47 theme high-intensity 567:580 arg1 training 624:631 light-intensity training 608:631 light-intensity training (LIT) 608:637 METHODS AND RESULTS A rat model was used to examine the intestinal microbiota responses to four activity conditions, including: high-intensity interval training (HIIT), light-intensity training (LIT), sedentary and normal control, each containing two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet. 28276612 4 47 theme high-intensity 567:580 arg1 HIIT 601:604 HIIT 601:604 HIIT 601:604 METHODS AND RESULTS A rat model was used to examine the intestinal microbiota responses to four activity conditions, including: high-intensity interval training (HIIT), light-intensity training (LIT), sedentary and normal control, each containing two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet. 28276612 4 47 theme high-intensity 567:580 arg1 each 670:673 each 670:673 each 670:673 METHODS AND RESULTS A rat model was used to examine the intestinal microbiota responses to four activity conditions, including: high-intensity interval training (HIIT), light-intensity training (LIT), sedentary and normal control, each containing two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet. 28276612 4 47 theme high-intensity 567:580 arg1 training 591:598 high-intensity interval training 567:598 high-intensity interval training (HIIT) 567:605 METHODS AND RESULTS A rat model was used to examine the intestinal microbiota responses to four activity conditions, including: high-intensity interval training (HIIT), light-intensity training (LIT), sedentary and normal control, each containing two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet. 28276612 6 48 from differences 1001:1011 arg1 microbiota 1027:1036 intestinal microbiota 1016:1036 intestinal microbiota 1016:1036 In rats fed SC, significant differences in intestinal microbiota were evident between exercised and nonexercised rats. 28276612 1 49 theme clinical 156:163 arg1 syndrome 197:204 metabolic syndrome 187:204 metabolic syndrome 187:204 AIMS Intestinal microbiota modulates the development of clinical conditions, including metabolic syndrome and obesity. 28276612 1 49 theme clinical 156:163 arg1 conditions 165:174 clinical conditions 156:174 clinical conditions 156:174 AIMS Intestinal microbiota modulates the development of clinical conditions, including metabolic syndrome and obesity. 28276612 1 49 theme clinical 156:163 arg1 obesity 210:216 obesity 210:216 obesity 210:216 AIMS Intestinal microbiota modulates the development of clinical conditions, including metabolic syndrome and obesity. 28276612 4 50 contain containing 675:684 arg2 conditions 702:711 two nutritional conditions 686:711 two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet 686:773 METHODS AND RESULTS A rat model was used to examine the intestinal microbiota responses to four activity conditions, including: high-intensity interval training (HIIT), light-intensity training (LIT), sedentary and normal control, each containing two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet. 28276612 4 50 contain containing 675:684 arg2 diet 770:773 standard chow (SC) diet 751:773 standard chow (SC) diet 751:773 METHODS AND RESULTS A rat model was used to examine the intestinal microbiota responses to four activity conditions, including: high-intensity interval training (HIIT), light-intensity training (LIT), sedentary and normal control, each containing two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet. 28276612 4 50 contain containing 675:684 arg1 training 591:598 high-intensity interval training 567:598 high-intensity interval training (HIIT) 567:605 METHODS AND RESULTS A rat model was used to examine the intestinal microbiota responses to four activity conditions, including: high-intensity interval training (HIIT), light-intensity training (LIT), sedentary and normal control, each containing two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet. 28276612 4 50 contain containing 675:684 arg2 diet 737:740 high-fat high-fructose diet 714:740 high-fat high-fructose diet (HF) 714:745 METHODS AND RESULTS A rat model was used to examine the intestinal microbiota responses to four activity conditions, including: high-intensity interval training (HIIT), light-intensity training (LIT), sedentary and normal control, each containing two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet. 28276612 4 50 contain containing 675:684 arg1 each 670:673 each 670:673 each 670:673 METHODS AND RESULTS A rat model was used to examine the intestinal microbiota responses to four activity conditions, including: high-intensity interval training (HIIT), light-intensity training (LIT), sedentary and normal control, each containing two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet. 28276612 7 51 theme SC-fed 1170:1175 arg1 rats 1177:1180 SC-fed rats 1170:1180 SC-fed rats 1170:1180 Both LIT and HIIT induced significant differences in intestinal microbiota in SC-fed rats compared to their respective SC-fed controls. 28276612 11 52 theme gut 1813:1815 arg1 health 1817:1822 gut health 1813:1822 gut health 1813:1822 SIGNIFICANCE AND IMPACT OF THE STUDY The importance of diet-exercise interaction is extended to the level of intestinal bacteria and gut health. 28276612 9 53 theme significant 1451:1461 arg1 effect 1463:1468 a significant effect 1449:1468 a significant effect of exercise on microbiota composition 1449:1506 CONCLUSIONS While a significant effect of exercise on microbiota composition occurred in SC-fed rats, the HF-fed rats microbiota showed little response. 28276612 7 54 from differences 1130:1140 arg1 microbiota 1156:1165 intestinal microbiota 1145:1165 intestinal microbiota 1145:1165 Both LIT and HIIT induced significant differences in intestinal microbiota in SC-fed rats compared to their respective SC-fed controls. 28276612 7 54 from differences 1130:1140 arg1 rats 1177:1180 SC-fed rats 1170:1180 SC-fed rats 1170:1180 Both LIT and HIIT induced significant differences in intestinal microbiota in SC-fed rats compared to their respective SC-fed controls. 28276612 11 55 theme bacteria 1800:1807 arg1 level 1780:1784 the level 1776:1784 the level of intestinal bacteria and gut health 1776:1822 SIGNIFICANCE AND IMPACT OF THE STUDY The importance of diet-exercise interaction is extended to the level of intestinal bacteria and gut health. 28276612 11 56 dep SIGNIFICANCE 1680:1691 arg1 importance 1721:1730 The importance 1717:1730 SIGNIFICANCE AND IMPACT OF THE STUDY The importance of diet-exercise interaction 1680:1759 SIGNIFICANCE AND IMPACT OF THE STUDY The importance of diet-exercise interaction is extended to the level of intestinal bacteria and gut health. 28276612 10 57 theme HF 1610:1611 arg1 diet 1613:1616 a HF diet 1608:1616 a HF diet 1608:1616 These data suggest that a HF diet prevented microbiota differentiation in response to exercise. 28276612 4 58 theme standard 751:758 arg1 conditions 702:711 two nutritional conditions 686:711 two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet 686:773 METHODS AND RESULTS A rat model was used to examine the intestinal microbiota responses to four activity conditions, including: high-intensity interval training (HIIT), light-intensity training (LIT), sedentary and normal control, each containing two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet. 28276612 4 58 theme standard 751:758 arg1 diet 770:773 standard chow (SC) diet 751:773 standard chow (SC) diet 751:773 METHODS AND RESULTS A rat model was used to examine the intestinal microbiota responses to four activity conditions, including: high-intensity interval training (HIIT), light-intensity training (LIT), sedentary and normal control, each containing two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet. 28276612 1 59 theme Intestinal 105:114 arg1 microbiota 116:125 AIMS Intestinal microbiota 100:125 AIMS Intestinal microbiota 100:125 AIMS Intestinal microbiota modulates the development of clinical conditions, including metabolic syndrome and obesity. 28276612 0 60 from microbiota 80:89 arg1 rats 94:97 rats 94:97 rats 94:97 A gut reaction: the combined influence of exercise and diet on gastrointestinal microbiota in rats. 28276612 8 61 theme bacterial 1269:1277 arg1 phylotypes 1279:1288 the exercise-induced bacterial phylotypes 1248:1288 the exercise-induced bacterial phylotypes 1248:1288 Characterization of the exercise-induced bacterial phylotypes indicated an increase in bacteria likely capable of degrading resistant polysaccharides and an increase in short chain fatty acid producers. 28276612 1 62 theme metabolic 187:195 arg1 syndrome 197:204 metabolic syndrome 187:204 metabolic syndrome 187:204 AIMS Intestinal microbiota modulates the development of clinical conditions, including metabolic syndrome and obesity. 28276612 5 63 theme activity 839:846 arg1 conditions 848:857 activity conditions 839:857 activity conditions 839:857 No significant differences in microbiota were apparent between activity conditions in rats fed a HF diet but changes in the presence/absence of phylotypes were observed in the LIT and HIIT groups. 28276612 11 64 theme interaction 1749:1759 arg1 importance 1721:1730 The importance 1717:1730 SIGNIFICANCE AND IMPACT OF THE STUDY The importance of diet-exercise interaction 1680:1759 SIGNIFICANCE AND IMPACT OF THE STUDY The importance of diet-exercise interaction is extended to the level of intestinal bacteria and gut health. 28276612 3 65 from influence 401:409 arg1 process 430:436 the process 426:436 the process 426:436 This study aimed to investigate the ability of exercise to re-shape the intestinal microbiota and the influence of the diet on the process. 28276612 7 66 theme intestinal 1145:1154 arg1 microbiota 1156:1165 intestinal microbiota 1145:1165 intestinal microbiota 1145:1165 Both LIT and HIIT induced significant differences in intestinal microbiota in SC-fed rats compared to their respective SC-fed controls. 28276612 5 67 from rats 862:865 arg1 apparent 822:829 apparent 822:829 apparent 822:829 No significant differences in microbiota were apparent between activity conditions in rats fed a HF diet but changes in the presence/absence of phylotypes were observed in the LIT and HIIT groups. 28276612 3 68 theme re-shape 358:365 arg1 microbiota 382:391 the intestinal microbiota 367:391 the intestinal microbiota 367:391 This study aimed to investigate the ability of exercise to re-shape the intestinal microbiota and the influence of the diet on the process. 28276612 4 69 theme rat 461:463 arg1 model 465:469 A rat model 459:469 A rat model 459:469 METHODS AND RESULTS A rat model was used to examine the intestinal microbiota responses to four activity conditions, including: high-intensity interval training (HIIT), light-intensity training (LIT), sedentary and normal control, each containing two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet. 28276612 9 70 theme HF-fed 1537:1542 arg1 rats 1544:1547 the HF-fed rats 1533:1547 the HF-fed rats microbiota showed little response 1533:1581 CONCLUSIONS While a significant effect of exercise on microbiota composition occurred in SC-fed rats, the HF-fed rats microbiota showed little response. 28276612 5 71 theme phylotypes 920:929 arg1 presence/absence 900:915 the presence/absence 896:915 the presence/absence of phylotypes 896:929 No significant differences in microbiota were apparent between activity conditions in rats fed a HF diet but changes in the presence/absence of phylotypes were observed in the LIT and HIIT groups. 28276612 3 72 theme exercise 346:353 arg1 ability 335:341 the ability 331:341 the ability of exercise to re-shape the intestinal microbiota and the influence of the diet on the process 331:436 This study aimed to investigate the ability of exercise to re-shape the intestinal microbiota and the influence of the diet on the process. 28276612 8 73 theme capable 1331:1337 arg1 bacteria 1315:1322 bacteria 1315:1322 bacteria likely capable of degrading resistant polysaccharides 1315:1376 Characterization of the exercise-induced bacterial phylotypes indicated an increase in bacteria likely capable of degrading resistant polysaccharides and an increase in short chain fatty acid producers. 28276612 0 74 theme gut 2:4 arg1 reaction 6:13 A gut reaction 0:13 A gut reaction 0:13 A gut reaction: the combined influence of exercise and diet on gastrointestinal microbiota in rats. 28276612 8 75 from increase 1303:1310 arg1 bacteria 1315:1322 bacteria 1315:1322 bacteria likely capable of degrading resistant polysaccharides 1315:1376 Characterization of the exercise-induced bacterial phylotypes indicated an increase in bacteria likely capable of degrading resistant polysaccharides and an increase in short chain fatty acid producers. 28276612 8 75 from increase 1303:1310 arg1 producers 1420:1428 short chain fatty acid producers 1397:1428 short chain fatty acid producers 1397:1428 Characterization of the exercise-induced bacterial phylotypes indicated an increase in bacteria likely capable of degrading resistant polysaccharides and an increase in short chain fatty acid producers. 28276612 6 76 theme significant 989:999 arg1 differences 1001:1011 significant differences 989:1011 significant differences in intestinal microbiota 989:1036 In rats fed SC, significant differences in intestinal microbiota were evident between exercised and nonexercised rats. 28276612 4 77 theme activity 535:542 arg1 conditions 544:553 four activity conditions 530:553 four activity conditions 530:553 METHODS AND RESULTS A rat model was used to examine the intestinal microbiota responses to four activity conditions, including: high-intensity interval training (HIIT), light-intensity training (LIT), sedentary and normal control, each containing two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet. 28276612 4 77 theme activity 535:542 arg1 training 591:598 high-intensity interval training 567:598 high-intensity interval training (HIIT) 567:605 METHODS AND RESULTS A rat model was used to examine the intestinal microbiota responses to four activity conditions, including: high-intensity interval training (HIIT), light-intensity training (LIT), sedentary and normal control, each containing two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet. 28276612 10 78 theme microbiota 1628:1637 arg1 differentiation 1639:1653 microbiota differentiation 1628:1653 microbiota differentiation 1628:1653 These data suggest that a HF diet prevented microbiota differentiation in response to exercise. 28276612 4 79 used used 475:478 arg2 model 465:469 A rat model 459:469 A rat model 459:469 METHODS AND RESULTS A rat model was used to examine the intestinal microbiota responses to four activity conditions, including: high-intensity interval training (HIIT), light-intensity training (LIT), sedentary and normal control, each containing two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet. 28276612 3 80 theme intestinal 371:380 arg1 microbiota 382:391 the intestinal microbiota 367:391 the intestinal microbiota 367:391 This study aimed to investigate the ability of exercise to re-shape the intestinal microbiota and the influence of the diet on the process. 28276612 4 81 theme high-fat 714:721 arg1 conditions 702:711 two nutritional conditions 686:711 two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet 686:773 METHODS AND RESULTS A rat model was used to examine the intestinal microbiota responses to four activity conditions, including: high-intensity interval training (HIIT), light-intensity training (LIT), sedentary and normal control, each containing two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet. 28276612 4 81 theme high-fat 714:721 arg1 HF 743:744 HF 743:744 HF 743:744 METHODS AND RESULTS A rat model was used to examine the intestinal microbiota responses to four activity conditions, including: high-intensity interval training (HIIT), light-intensity training (LIT), sedentary and normal control, each containing two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet. 28276612 4 81 theme high-fat 714:721 arg1 diet 737:740 high-fat high-fructose diet 714:740 high-fat high-fructose diet (HF) 714:745 METHODS AND RESULTS A rat model was used to examine the intestinal microbiota responses to four activity conditions, including: high-intensity interval training (HIIT), light-intensity training (LIT), sedentary and normal control, each containing two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet. 28276612 0 82 theme combined 20:27 arg1 influence 29:37 the combined influence 16:37 the combined influence of exercise and diet on gastrointestinal microbiota in rats 16:97 A gut reaction: the combined influence of exercise and diet on gastrointestinal microbiota in rats. 28276612 4 83 theme microbiota 506:515 arg1 responses 517:525 the intestinal microbiota responses 491:525 the intestinal microbiota responses to four activity conditions, including: high-intensity interval training (HIIT), light-intensity training (LIT), sedentary and normal control, each containing two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet 491:773 METHODS AND RESULTS A rat model was used to examine the intestinal microbiota responses to four activity conditions, including: high-intensity interval training (HIIT), light-intensity training (LIT), sedentary and normal control, each containing two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet. 28276612 4 84 theme SC 766:767 arg1 conditions 702:711 two nutritional conditions 686:711 two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet 686:773 METHODS AND RESULTS A rat model was used to examine the intestinal microbiota responses to four activity conditions, including: high-intensity interval training (HIIT), light-intensity training (LIT), sedentary and normal control, each containing two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet. 28276612 4 84 theme SC 766:767 arg1 diet 770:773 standard chow (SC) diet 751:773 standard chow (SC) diet 751:773 METHODS AND RESULTS A rat model was used to examine the intestinal microbiota responses to four activity conditions, including: high-intensity interval training (HIIT), light-intensity training (LIT), sedentary and normal control, each containing two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet. 28276612 6 85 theme nonexercised 1073:1084 arg1 rats 1086:1089 exercised and nonexercised rats 1059:1089 exercised and nonexercised rats 1059:1089 In rats fed SC, significant differences in intestinal microbiota were evident between exercised and nonexercised rats. 28276612 4 86 theme chow 760:763 arg1 conditions 702:711 two nutritional conditions 686:711 two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet 686:773 METHODS AND RESULTS A rat model was used to examine the intestinal microbiota responses to four activity conditions, including: high-intensity interval training (HIIT), light-intensity training (LIT), sedentary and normal control, each containing two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet. 28276612 4 86 theme chow 760:763 arg1 diet 770:773 standard chow (SC) diet 751:773 standard chow (SC) diet 751:773 METHODS AND RESULTS A rat model was used to examine the intestinal microbiota responses to four activity conditions, including: high-intensity interval training (HIIT), light-intensity training (LIT), sedentary and normal control, each containing two nutritional conditions: high-fat high-fructose diet (HF) and standard chow (SC) diet. 28276612 9 87 from effect 1463:1468 arg1 composition 1496:1506 microbiota composition 1485:1506 microbiota composition 1485:1506 CONCLUSIONS While a significant effect of exercise on microbiota composition occurred in SC-fed rats, the HF-fed rats microbiota showed little response. 28276612 6 88 theme exercised 1059:1067 arg1 rats 1086:1089 exercised and nonexercised rats 1059:1089 exercised and nonexercised rats 1059:1089 In rats fed SC, significant differences in intestinal microbiota were evident between exercised and nonexercised rats. 28276612 11 89 theme STUDY 1711:1715 arg1 IMPACT 1697:1702 IMPACT 1697:1702 IMPACT 1697:1702 SIGNIFICANCE AND IMPACT OF THE STUDY The importance of diet-exercise interaction is extended to the level of intestinal bacteria and gut health. 28276612 11 89 theme STUDY 1711:1715 arg1 SIGNIFICANCE 1680:1691 SIGNIFICANCE 1680:1691 SIGNIFICANCE 1680:1691 SIGNIFICANCE AND IMPACT OF THE STUDY The importance of diet-exercise interaction is extended to the level of intestinal bacteria and gut health. 28276612 8 90 theme chain 1403:1407 arg1 producers 1420:1428 short chain fatty acid producers 1397:1428 short chain fatty acid producers 1397:1428 Characterization of the exercise-induced bacterial phylotypes indicated an increase in bacteria likely capable of degrading resistant polysaccharides and an increase in short chain fatty acid producers. 28276612 7 91 theme respective 1200:1209 arg1 controls 1218:1225 their respective SC-fed controls 1194:1225 their respective SC-fed controls 1194:1225 Both LIT and HIIT induced significant differences in intestinal microbiota in SC-fed rats compared to their respective SC-fed controls. 28276612 8 92 theme acid 1415:1418 arg1 producers 1420:1428 short chain fatty acid producers 1397:1428 short chain fatty acid producers 1397:1428 Characterization of the exercise-induced bacterial phylotypes indicated an increase in bacteria likely capable of degrading resistant polysaccharides and an increase in short chain fatty acid producers. 28276612 6 93 from evident 1043:1049 arg1 rats 976:979 rats 976:979 rats fed SC 976:986 In rats fed SC, significant differences in intestinal microbiota were evident between exercised and nonexercised rats. 26099801 6 0 theme genes 1005:1009 arg1 importance 981:990 The importance 977:990 The importance of these LRX genes for plant development and particularly cell wall formation 977:1068 The importance of these LRX genes for plant development and particularly cell wall formation was investigated. 26099801 8 1 from number 1299:1304 arg1 mutants 1353:1359 the mutants 1349:1359 the mutants 1349:1359 Analysis of cell wall composition revealed a number of changes to cell wall polysaccharides in the mutants. 26099801 10 2 from complexity 1489:1498 arg1 structures 1524:1533 cell wall structures 1514:1533 cell wall structures in the lrx mutants 1514:1552 Due to the complexity of changes in cell wall structures in the lrx mutants, the exact function of LRX proteins remains to be determined. 26099801 1 3 contain containing 282:291 arg2 features 305:312 the typical features 293:312 the typical features of this class of structural hydroxyproline-rich glycoproteins (HRGPs) 293:382 BACKGROUND Leucine-rich repeat extensins (LRXs) are extracellular proteins consisting of an N-terminal leucine-rich repeat (LRR) domain and a C-terminal extensin domain containing the typical features of this class of structural hydroxyproline-rich glycoproteins (HRGPs). 26099801 1 3 contain containing 282:291 arg1 domain 275:280 a C-terminal extensin domain 253:280 a C-terminal extensin domain containing the typical features of this class of structural hydroxyproline-rich glycoproteins (HRGPs) 253:382 BACKGROUND Leucine-rich repeat extensins (LRXs) are extracellular proteins consisting of an N-terminal leucine-rich repeat (LRR) domain and a C-terminal extensin domain containing the typical features of this class of structural hydroxyproline-rich glycoproteins (HRGPs). 26099801 1 4 theme C-terminal 255:264 arg1 domain 275:280 a C-terminal extensin domain 253:280 a C-terminal extensin domain containing the typical features of this class of structural hydroxyproline-rich glycoproteins (HRGPs) 253:382 BACKGROUND Leucine-rich repeat extensins (LRXs) are extracellular proteins consisting of an N-terminal leucine-rich repeat (LRR) domain and a C-terminal extensin domain containing the typical features of this class of structural hydroxyproline-rich glycoproteins (HRGPs). 26099801 10 5 from changes 1503:1509 arg1 structures 1524:1533 cell wall structures 1514:1533 cell wall structures in the lrx mutants 1514:1552 Due to the complexity of changes in cell wall structures in the lrx mutants, the exact function of LRX proteins remains to be determined. 26099801 1 6 theme extracellular 165:177 arg1 proteins 179:186 extracellular proteins 165:186 extracellular proteins consisting of an N-terminal leucine-rich repeat (LRR) domain and a C-terminal extensin domain containing the typical features of this class of structural hydroxyproline-rich glycoproteins (HRGPs) 165:382 BACKGROUND Leucine-rich repeat extensins (LRXs) are extracellular proteins consisting of an N-terminal leucine-rich repeat (LRR) domain and a C-terminal extensin domain containing the typical features of this class of structural hydroxyproline-rich glycoproteins (HRGPs). 26099801 1 6 theme extracellular 165:177 arg1 extensins 144:152 BACKGROUND Leucine-rich repeat extensins 113:152 BACKGROUND Leucine-rich repeat extensins (LRXs) 113:159 BACKGROUND Leucine-rich repeat extensins (LRXs) are extracellular proteins consisting of an N-terminal leucine-rich repeat (LRR) domain and a C-terminal extensin domain containing the typical features of this class of structural hydroxyproline-rich glycoproteins (HRGPs). 26099801 5 7 theme gene 835:838 arg1 family 840:845 The LRX gene family 827:845 RESULTS The LRX gene family of Arabidopsis 819:860 RESULTS The LRX gene family of Arabidopsis consists of eleven members, of which LRX3, LRX4, and LRX5 are expressed in aerial organs, such as leaves and stem. 26099801 7 8 theme double 1181:1186 arg1 mutants 1199:1205 double and triple mutants 1181:1205 double and triple mutants 1181:1205 Synergistic effects of mutations with gradually more severe growth retardation phenotypes in double and triple mutants suggest a similar function of the three genes. 26099801 3 9 dep LRX1 591:594 arg1 the 567:569 the 567:569 the 567:569 Based on the analysis of the root hair-expressed LRX1 and LRX2 of Arabidopsis thaliana, LRX proteins are important for cell wall development. 26099801 7 10 with mutations 1111:1119 arg1 phenotypes 1167:1176 gradually more severe growth retardation phenotypes 1126:1176 gradually more severe growth retardation phenotypes in double and triple mutants 1126:1205 Synergistic effects of mutations with gradually more severe growth retardation phenotypes in double and triple mutants suggest a similar function of the three genes. 26099801 9 11 dep CONCLUSIONS 1362:1372 arg1 CONCLUSIONS 1362:1372 CONCLUSIONS 1362:1372 CONCLUSIONS LRX3, LRX4, and LRX5 1362:1393 CONCLUSIONS LRX3, LRX4, and LRX5, and most likely LRX proteins in general, are important for cell wall development. 26099801 9 11 dep CONCLUSIONS 1362:1372 arg1 LRX4 1380:1383 LRX4 1380:1383 LRX4 1380:1383 CONCLUSIONS LRX3, LRX4, and LRX5, and most likely LRX proteins in general, are important for cell wall development. 26099801 9 11 dep CONCLUSIONS 1362:1372 arg1 LRX5 1390:1393 LRX5 1390:1393 LRX5 1390:1393 CONCLUSIONS LRX3, LRX4, and LRX5, and most likely LRX proteins in general, are important for cell wall development. 26099801 9 11 dep CONCLUSIONS 1362:1372 arg1 LRX3 1374:1377 LRX3 1374:1377 LRX3 1374:1377 CONCLUSIONS LRX3, LRX4, and LRX5, and most likely LRX proteins in general, are important for cell wall development. 26099801 10 12 theme cell 1514:1517 arg1 structures 1524:1533 cell wall structures 1514:1533 cell wall structures in the lrx mutants 1514:1552 Due to the complexity of changes in cell wall structures in the lrx mutants, the exact function of LRX proteins remains to be determined. 26099801 3 13 theme root 571:574 arg1 LRX1 591:594 root hair-expressed LRX1 571:594 root hair-expressed LRX1 571:594 Based on the analysis of the root hair-expressed LRX1 and LRX2 of Arabidopsis thaliana, LRX proteins are important for cell wall development. 26099801 1 14 theme leucine-rich 216:227 arg1 domain 242:247 an N-terminal leucine-rich repeat (LRR) domain 202:247 an N-terminal leucine-rich repeat (LRR) domain 202:247 BACKGROUND Leucine-rich repeat extensins (LRXs) are extracellular proteins consisting of an N-terminal leucine-rich repeat (LRR) domain and a C-terminal extensin domain containing the typical features of this class of structural hydroxyproline-rich glycoproteins (HRGPs). 26099801 10 15 theme changes 1503:1509 arg1 complexity 1489:1498 the complexity 1485:1498 the complexity of changes in cell wall structures in the lrx mutants 1485:1552 Due to the complexity of changes in cell wall structures in the lrx mutants, the exact function of LRX proteins remains to be determined. 26099801 4 16 from mutations 779:787 arg1 genes 796:800 LRX genes 792:800 LRX genes 792:800 The importance of LRX proteins in non-root hair cells and on the structural changes induced by mutations in LRX genes remains elusive. 26099801 1 17 theme BACKGROUND 113:122 arg1 proteins 179:186 extracellular proteins 165:186 extracellular proteins consisting of an N-terminal leucine-rich repeat (LRR) domain and a C-terminal extensin domain containing the typical features of this class of structural hydroxyproline-rich glycoproteins (HRGPs) 165:382 BACKGROUND Leucine-rich repeat extensins (LRXs) are extracellular proteins consisting of an N-terminal leucine-rich repeat (LRR) domain and a C-terminal extensin domain containing the typical features of this class of structural hydroxyproline-rich glycoproteins (HRGPs). 26099801 1 17 theme BACKGROUND 113:122 arg1 LRXs 155:158 LRXs 155:158 LRXs 155:158 BACKGROUND Leucine-rich repeat extensins (LRXs) are extracellular proteins consisting of an N-terminal leucine-rich repeat (LRR) domain and a C-terminal extensin domain containing the typical features of this class of structural hydroxyproline-rich glycoproteins (HRGPs). 26099801 1 17 theme BACKGROUND 113:122 arg1 extensins 144:152 BACKGROUND Leucine-rich repeat extensins 113:152 BACKGROUND Leucine-rich repeat extensins (LRXs) 113:159 BACKGROUND Leucine-rich repeat extensins (LRXs) are extracellular proteins consisting of an N-terminal leucine-rich repeat (LRR) domain and a C-terminal extensin domain containing the typical features of this class of structural hydroxyproline-rich glycoproteins (HRGPs). 26099801 8 18 theme changes 1309:1315 arg1 number 1299:1304 a number 1297:1304 a number of changes to cell wall polysaccharides in the mutants 1297:1359 Analysis of cell wall composition revealed a number of changes to cell wall polysaccharides in the mutants. 26099801 3 19 theme LRX2 600:603 arg1 analysis 555:562 the analysis 551:562 the analysis of the root hair-expressed LRX1 and LRX2 of Arabidopsis thaliana 551:627 Based on the analysis of the root hair-expressed LRX1 and LRX2 of Arabidopsis thaliana, LRX proteins are important for cell wall development. 26099801 9 20 theme LRX 1412:1414 arg1 proteins 1416:1423 LRX proteins 1412:1423 LRX proteins in general 1412:1434 CONCLUSIONS LRX3, LRX4, and LRX5, and most likely LRX proteins in general, are important for cell wall development. 26099801 7 21 from phenotypes 1167:1176 arg1 mutants 1199:1205 double and triple mutants 1181:1205 double and triple mutants 1181:1205 Synergistic effects of mutations with gradually more severe growth retardation phenotypes in double and triple mutants suggest a similar function of the three genes. 26099801 11 22 theme plant 1787:1791 arg1 development 1793:1803 proper plant development 1780:1803 proper plant development 1780:1803 The increasingly strong growth-defect phenotypes in double and triple mutants suggests that the LRX proteins have similar functions and that they are important for proper plant development. 26099801 1 23 theme class 322:326 arg1 features 305:312 the typical features 293:312 the typical features of this class of structural hydroxyproline-rich glycoproteins (HRGPs) 293:382 BACKGROUND Leucine-rich repeat extensins (LRXs) are extracellular proteins consisting of an N-terminal leucine-rich repeat (LRR) domain and a C-terminal extensin domain containing the typical features of this class of structural hydroxyproline-rich glycoproteins (HRGPs). 26099801 3 24 theme LRX1 591:594 arg1 analysis 555:562 the analysis 551:562 the analysis of the root hair-expressed LRX1 and LRX2 of Arabidopsis thaliana 551:627 Based on the analysis of the root hair-expressed LRX1 and LRX2 of Arabidopsis thaliana, LRX proteins are important for cell wall development. 26099801 0 25 theme wall 68:71 arg1 composition 73:83 cell wall composition 63:83 cell wall composition 63:83 Arabidopsis leucine-rich repeat extensin (LRX) proteins modify cell wall composition and influence plant growth. 26099801 1 26 theme structural 331:340 arg1 HRGPs 377:381 HRGPs 377:381 HRGPs 377:381 BACKGROUND Leucine-rich repeat extensins (LRXs) are extracellular proteins consisting of an N-terminal leucine-rich repeat (LRR) domain and a C-terminal extensin domain containing the typical features of this class of structural hydroxyproline-rich glycoproteins (HRGPs). 26099801 1 26 theme structural 331:340 arg1 glycoproteins 362:374 structural hydroxyproline-rich glycoproteins 331:374 structural hydroxyproline-rich glycoproteins (HRGPs) 331:382 BACKGROUND Leucine-rich repeat extensins (LRXs) are extracellular proteins consisting of an N-terminal leucine-rich repeat (LRR) domain and a C-terminal extensin domain containing the typical features of this class of structural hydroxyproline-rich glycoproteins (HRGPs). 26099801 8 27 theme wall 1271:1274 arg1 composition 1276:1286 cell wall composition 1266:1286 cell wall composition 1266:1286 Analysis of cell wall composition revealed a number of changes to cell wall polysaccharides in the mutants. 26099801 11 28 theme growth-defect 1640:1652 arg1 phenotypes 1654:1663 The increasingly strong growth-defect phenotypes 1616:1663 The increasingly strong growth-defect phenotypes in double and triple mutants 1616:1692 The increasingly strong growth-defect phenotypes in double and triple mutants suggests that the LRX proteins have similar functions and that they are important for proper plant development. 26099801 1 29 theme glycoproteins 362:374 arg1 class 322:326 this class 317:326 this class of structural hydroxyproline-rich glycoproteins (HRGPs) 317:382 BACKGROUND Leucine-rich repeat extensins (LRXs) are extracellular proteins consisting of an N-terminal leucine-rich repeat (LRR) domain and a C-terminal extensin domain containing the typical features of this class of structural hydroxyproline-rich glycoproteins (HRGPs). 26099801 1 30 theme repeat 137:142 arg1 proteins 179:186 extracellular proteins 165:186 extracellular proteins consisting of an N-terminal leucine-rich repeat (LRR) domain and a C-terminal extensin domain containing the typical features of this class of structural hydroxyproline-rich glycoproteins (HRGPs) 165:382 BACKGROUND Leucine-rich repeat extensins (LRXs) are extracellular proteins consisting of an N-terminal leucine-rich repeat (LRR) domain and a C-terminal extensin domain containing the typical features of this class of structural hydroxyproline-rich glycoproteins (HRGPs). 26099801 1 30 theme repeat 137:142 arg1 LRXs 155:158 LRXs 155:158 LRXs 155:158 BACKGROUND Leucine-rich repeat extensins (LRXs) are extracellular proteins consisting of an N-terminal leucine-rich repeat (LRR) domain and a C-terminal extensin domain containing the typical features of this class of structural hydroxyproline-rich glycoproteins (HRGPs). 26099801 1 30 theme repeat 137:142 arg1 extensins 144:152 BACKGROUND Leucine-rich repeat extensins 113:152 BACKGROUND Leucine-rich repeat extensins (LRXs) 113:159 BACKGROUND Leucine-rich repeat extensins (LRXs) are extracellular proteins consisting of an N-terminal leucine-rich repeat (LRR) domain and a C-terminal extensin domain containing the typical features of this class of structural hydroxyproline-rich glycoproteins (HRGPs). 26099801 10 31 theme lrx 1542:1544 arg1 mutants 1546:1552 the lrx mutants 1538:1552 the lrx mutants 1538:1552 Due to the complexity of changes in cell wall structures in the lrx mutants, the exact function of LRX proteins remains to be determined. 26099801 0 32 theme plant 99:103 arg1 growth 105:110 plant growth 99:110 plant growth 99:110 Arabidopsis leucine-rich repeat extensin (LRX) proteins modify cell wall composition and influence plant growth. 26099801 9 33 theme cell 1455:1458 arg1 development 1465:1475 cell wall development 1455:1475 cell wall development 1455:1475 CONCLUSIONS LRX3, LRX4, and LRX5, and most likely LRX proteins in general, are important for cell wall development. 26099801 0 34 theme cell 63:66 arg1 composition 73:83 cell wall composition 63:83 cell wall composition 63:83 Arabidopsis leucine-rich repeat extensin (LRX) proteins modify cell wall composition and influence plant growth. 26099801 4 35 theme proteins 706:713 arg1 importance 688:697 The importance 684:697 The importance of LRX proteins in non-root hair cells and on the structural changes induced by mutations in LRX genes 684:800 The importance of LRX proteins in non-root hair cells and on the structural changes induced by mutations in LRX genes remains elusive. 26099801 0 36 theme Arabidopsis 0:10 arg1 proteins 47:54 Arabidopsis leucine-rich repeat extensin (LRX) proteins 0:54 Arabidopsis leucine-rich repeat extensin (LRX) proteins 0:54 Arabidopsis leucine-rich repeat extensin (LRX) proteins modify cell wall composition and influence plant growth. 26099801 1 37 theme extensin 266:273 arg1 domain 275:280 a C-terminal extensin domain 253:280 a C-terminal extensin domain containing the typical features of this class of structural hydroxyproline-rich glycoproteins (HRGPs) 253:382 BACKGROUND Leucine-rich repeat extensins (LRXs) are extracellular proteins consisting of an N-terminal leucine-rich repeat (LRR) domain and a C-terminal extensin domain containing the typical features of this class of structural hydroxyproline-rich glycoproteins (HRGPs). 26099801 2 38 theme interaction 421:431 arg1 partner 433:439 an interaction partner 418:439 an interaction partner 418:439 The LRR domain is likely to bind an interaction partner, whereas the extensin domain has an anchoring function to insolubilize the protein in the cell wall. 26099801 4 39 theme non-root 718:725 arg1 cells 732:736 non-root hair cells 718:736 non-root hair cells 718:736 The importance of LRX proteins in non-root hair cells and on the structural changes induced by mutations in LRX genes remains elusive. 26099801 10 40 theme exact 1559:1563 arg1 function 1565:1572 the exact function 1555:1572 the exact function of LRX proteins 1555:1588 Due to the complexity of changes in cell wall structures in the lrx mutants, the exact function of LRX proteins remains to be determined. 26099801 0 41 theme repeat 25:30 arg1 proteins 47:54 Arabidopsis leucine-rich repeat extensin (LRX) proteins 0:54 Arabidopsis leucine-rich repeat extensin (LRX) proteins 0:54 Arabidopsis leucine-rich repeat extensin (LRX) proteins modify cell wall composition and influence plant growth. 26099801 8 42 theme cell 1320:1323 arg1 polysaccharides 1330:1344 cell wall polysaccharides 1320:1344 cell wall polysaccharides 1320:1344 Analysis of cell wall composition revealed a number of changes to cell wall polysaccharides in the mutants. 26099801 1 43 theme typical 297:303 arg1 features 305:312 the typical features 293:312 the typical features of this class of structural hydroxyproline-rich glycoproteins (HRGPs) 293:382 BACKGROUND Leucine-rich repeat extensins (LRXs) are extracellular proteins consisting of an N-terminal leucine-rich repeat (LRR) domain and a C-terminal extensin domain containing the typical features of this class of structural hydroxyproline-rich glycoproteins (HRGPs). 26099801 3 44 theme Arabidopsis 608:618 arg1 thaliana 620:627 Arabidopsis thaliana 608:627 Arabidopsis thaliana 608:627 Based on the analysis of the root hair-expressed LRX1 and LRX2 of Arabidopsis thaliana, LRX proteins are important for cell wall development. 26099801 5 45 dep RESULTS 819:825 arg1 family 840:845 The LRX gene family 827:845 RESULTS The LRX gene family of Arabidopsis 819:860 RESULTS The LRX gene family of Arabidopsis consists of eleven members, of which LRX3, LRX4, and LRX5 are expressed in aerial organs, such as leaves and stem. 26099801 10 46 theme proteins 1581:1588 arg1 function 1565:1572 the exact function 1555:1572 the exact function of LRX proteins 1555:1588 Due to the complexity of changes in cell wall structures in the lrx mutants, the exact function of LRX proteins remains to be determined. 26099801 11 47 contain have 1725:1728 arg2 functions 1738:1746 similar functions 1730:1746 similar functions 1730:1746 The increasingly strong growth-defect phenotypes in double and triple mutants suggests that the LRX proteins have similar functions and that they are important for proper plant development. 26099801 11 47 contain have 1725:1728 arg1 proteins 1716:1723 the LRX proteins 1708:1723 the LRX proteins 1708:1723 The increasingly strong growth-defect phenotypes in double and triple mutants suggests that the LRX proteins have similar functions and that they are important for proper plant development. 26099801 7 48 theme similar 1217:1223 arg1 function 1225:1232 a similar function 1215:1232 a similar function of the three genes 1215:1251 Synergistic effects of mutations with gradually more severe growth retardation phenotypes in double and triple mutants suggest a similar function of the three genes. 26099801 4 49 theme structural 749:758 arg1 changes 760:766 the structural changes 745:766 the structural changes induced by mutations in LRX genes 745:800 The importance of LRX proteins in non-root hair cells and on the structural changes induced by mutations in LRX genes remains elusive. 26099801 4 50 from importance 688:697 arg1 changes 760:766 the structural changes 745:766 the structural changes induced by mutations in LRX genes 745:800 The importance of LRX proteins in non-root hair cells and on the structural changes induced by mutations in LRX genes remains elusive. 26099801 4 50 from importance 688:697 arg1 cells 732:736 non-root hair cells 718:736 non-root hair cells 718:736 The importance of LRX proteins in non-root hair cells and on the structural changes induced by mutations in LRX genes remains elusive. 26099801 1 51 theme repeat 229:234 arg1 domain 242:247 an N-terminal leucine-rich repeat (LRR) domain 202:247 an N-terminal leucine-rich repeat (LRR) domain 202:247 BACKGROUND Leucine-rich repeat extensins (LRXs) are extracellular proteins consisting of an N-terminal leucine-rich repeat (LRR) domain and a C-terminal extensin domain containing the typical features of this class of structural hydroxyproline-rich glycoproteins (HRGPs). 26099801 1 52 theme LRR 237:239 arg1 domain 242:247 an N-terminal leucine-rich repeat (LRR) domain 202:247 an N-terminal leucine-rich repeat (LRR) domain 202:247 BACKGROUND Leucine-rich repeat extensins (LRXs) are extracellular proteins consisting of an N-terminal leucine-rich repeat (LRR) domain and a C-terminal extensin domain containing the typical features of this class of structural hydroxyproline-rich glycoproteins (HRGPs). 26099801 5 53 theme aerial 937:942 arg1 stem 971:974 stem 971:974 stem 971:974 RESULTS The LRX gene family of Arabidopsis consists of eleven members, of which LRX3, LRX4, and LRX5 are expressed in aerial organs, such as leaves and stem. 26099801 5 53 theme aerial 937:942 arg1 leaves 960:965 leaves 960:965 leaves 960:965 RESULTS The LRX gene family of Arabidopsis consists of eleven members, of which LRX3, LRX4, and LRX5 are expressed in aerial organs, such as leaves and stem. 26099801 5 53 theme aerial 937:942 arg1 organs 944:949 aerial organs 937:949 aerial organs 937:949 RESULTS The LRX gene family of Arabidopsis consists of eleven members, of which LRX3, LRX4, and LRX5 are expressed in aerial organs, such as leaves and stem. 26099801 9 54 from CONCLUSIONS 1362:1372 arg1 general 1428:1434 general 1428:1434 general 1428:1434 CONCLUSIONS LRX3, LRX4, and LRX5, and most likely LRX proteins in general, are important for cell wall development. 26099801 7 55 theme triple 1192:1197 arg1 mutants 1199:1205 double and triple mutants 1181:1205 double and triple mutants 1181:1205 Synergistic effects of mutations with gradually more severe growth retardation phenotypes in double and triple mutants suggest a similar function of the three genes. 26099801 6 56 theme LRX 1001:1003 arg1 genes 1005:1009 these LRX genes 995:1009 these LRX genes 995:1009 The importance of these LRX genes for plant development and particularly cell wall formation was investigated. 26099801 3 57 theme cell 661:664 arg1 development 671:681 cell wall development 661:681 cell wall development 661:681 Based on the analysis of the root hair-expressed LRX1 and LRX2 of Arabidopsis thaliana, LRX proteins are important for cell wall development. 26099801 4 58 theme LRX 792:794 arg1 genes 796:800 LRX genes 792:800 LRX genes 792:800 The importance of LRX proteins in non-root hair cells and on the structural changes induced by mutations in LRX genes remains elusive. 26099801 9 59 from proteins 1416:1423 arg1 general 1428:1434 general 1428:1434 general 1428:1434 CONCLUSIONS LRX3, LRX4, and LRX5, and most likely LRX proteins in general, are important for cell wall development. 26099801 7 60 theme growth 1148:1153 arg1 phenotypes 1167:1176 gradually more severe growth retardation phenotypes 1126:1176 gradually more severe growth retardation phenotypes in double and triple mutants 1126:1205 Synergistic effects of mutations with gradually more severe growth retardation phenotypes in double and triple mutants suggest a similar function of the three genes. 26099801 5 61 theme LRX 831:833 arg1 family 840:845 The LRX gene family 827:845 RESULTS The LRX gene family of Arabidopsis 819:860 RESULTS The LRX gene family of Arabidopsis consists of eleven members, of which LRX3, LRX4, and LRX5 are expressed in aerial organs, such as leaves and stem. 26099801 1 62 gly glycoproteins 362:374 arg1 HRGPs 377:381 HRGPs 377:381 HRGPs 377:381 BACKGROUND Leucine-rich repeat extensins (LRXs) are extracellular proteins consisting of an N-terminal leucine-rich repeat (LRR) domain and a C-terminal extensin domain containing the typical features of this class of structural hydroxyproline-rich glycoproteins (HRGPs). 26099801 1 62 gly glycoproteins 362:374 arg1 glycoproteins 362:374 structural hydroxyproline-rich glycoproteins 331:374 structural hydroxyproline-rich glycoproteins (HRGPs) 331:382 BACKGROUND Leucine-rich repeat extensins (LRXs) are extracellular proteins consisting of an N-terminal leucine-rich repeat (LRR) domain and a C-terminal extensin domain containing the typical features of this class of structural hydroxyproline-rich glycoproteins (HRGPs). 26099801 2 63 theme cell 531:534 arg1 wall 536:539 the cell wall 527:539 the cell wall 527:539 The LRR domain is likely to bind an interaction partner, whereas the extensin domain has an anchoring function to insolubilize the protein in the cell wall. 26099801 6 64 theme wall 1055:1058 arg1 formation 1060:1068 cell wall formation 1050:1068 cell wall formation 1050:1068 The importance of these LRX genes for plant development and particularly cell wall formation was investigated. 26099801 10 65 theme wall 1519:1522 arg1 structures 1524:1533 cell wall structures 1514:1533 cell wall structures in the lrx mutants 1514:1552 Due to the complexity of changes in cell wall structures in the lrx mutants, the exact function of LRX proteins remains to be determined. 26099801 11 66 theme triple 1679:1684 arg1 mutants 1686:1692 double and triple mutants 1668:1692 double and triple mutants 1668:1692 The increasingly strong growth-defect phenotypes in double and triple mutants suggests that the LRX proteins have similar functions and that they are important for proper plant development. 26099801 1 67 theme N-terminal 205:214 arg1 domain 242:247 an N-terminal leucine-rich repeat (LRR) domain 202:247 an N-terminal leucine-rich repeat (LRR) domain 202:247 BACKGROUND Leucine-rich repeat extensins (LRXs) are extracellular proteins consisting of an N-terminal leucine-rich repeat (LRR) domain and a C-terminal extensin domain containing the typical features of this class of structural hydroxyproline-rich glycoproteins (HRGPs). 26099801 1 68 theme Leucine-rich 124:135 arg1 proteins 179:186 extracellular proteins 165:186 extracellular proteins consisting of an N-terminal leucine-rich repeat (LRR) domain and a C-terminal extensin domain containing the typical features of this class of structural hydroxyproline-rich glycoproteins (HRGPs) 165:382 BACKGROUND Leucine-rich repeat extensins (LRXs) are extracellular proteins consisting of an N-terminal leucine-rich repeat (LRR) domain and a C-terminal extensin domain containing the typical features of this class of structural hydroxyproline-rich glycoproteins (HRGPs). 26099801 1 68 theme Leucine-rich 124:135 arg1 LRXs 155:158 LRXs 155:158 LRXs 155:158 BACKGROUND Leucine-rich repeat extensins (LRXs) are extracellular proteins consisting of an N-terminal leucine-rich repeat (LRR) domain and a C-terminal extensin domain containing the typical features of this class of structural hydroxyproline-rich glycoproteins (HRGPs). 26099801 1 68 theme Leucine-rich 124:135 arg1 extensins 144:152 BACKGROUND Leucine-rich repeat extensins 113:152 BACKGROUND Leucine-rich repeat extensins (LRXs) 113:159 BACKGROUND Leucine-rich repeat extensins (LRXs) are extracellular proteins consisting of an N-terminal leucine-rich repeat (LRR) domain and a C-terminal extensin domain containing the typical features of this class of structural hydroxyproline-rich glycoproteins (HRGPs). 26099801 2 69 from protein 516:522 arg1 wall 536:539 the cell wall 527:539 the cell wall 527:539 The LRR domain is likely to bind an interaction partner, whereas the extensin domain has an anchoring function to insolubilize the protein in the cell wall. 26099801 8 70 from mutants 1353:1359 arg1 number 1299:1304 a number 1297:1304 a number of changes to cell wall polysaccharides in the mutants 1297:1359 Analysis of cell wall composition revealed a number of changes to cell wall polysaccharides in the mutants. 26099801 11 71 theme strong 1633:1638 arg1 phenotypes 1654:1663 The increasingly strong growth-defect phenotypes 1616:1663 The increasingly strong growth-defect phenotypes in double and triple mutants 1616:1692 The increasingly strong growth-defect phenotypes in double and triple mutants suggests that the LRX proteins have similar functions and that they are important for proper plant development. 26099801 7 72 theme retardation 1155:1165 arg1 phenotypes 1167:1176 gradually more severe growth retardation phenotypes 1126:1176 gradually more severe growth retardation phenotypes in double and triple mutants 1126:1205 Synergistic effects of mutations with gradually more severe growth retardation phenotypes in double and triple mutants suggest a similar function of the three genes. 26099801 3 73 theme hair-expressed 576:589 arg1 LRX1 591:594 root hair-expressed LRX1 571:594 root hair-expressed LRX1 571:594 Based on the analysis of the root hair-expressed LRX1 and LRX2 of Arabidopsis thaliana, LRX proteins are important for cell wall development. 26099801 2 74 theme anchoring 477:485 arg1 function 487:494 an anchoring function 474:494 an anchoring function to insolubilize the protein in the cell wall 474:539 The LRR domain is likely to bind an interaction partner, whereas the extensin domain has an anchoring function to insolubilize the protein in the cell wall. 26099801 7 75 theme severe 1141:1146 arg1 phenotypes 1167:1176 gradually more severe growth retardation phenotypes 1126:1176 gradually more severe growth retardation phenotypes in double and triple mutants 1126:1205 Synergistic effects of mutations with gradually more severe growth retardation phenotypes in double and triple mutants suggest a similar function of the three genes. 26099801 5 76 theme Arabidopsis 850:860 arg1 family 840:845 The LRX gene family 827:845 RESULTS The LRX gene family of Arabidopsis 819:860 RESULTS The LRX gene family of Arabidopsis consists of eleven members, of which LRX3, LRX4, and LRX5 are expressed in aerial organs, such as leaves and stem. 26099801 11 77 from phenotypes 1654:1663 arg1 mutants 1686:1692 double and triple mutants 1668:1692 double and triple mutants 1668:1692 The increasingly strong growth-defect phenotypes in double and triple mutants suggests that the LRX proteins have similar functions and that they are important for proper plant development. 26099801 11 78 theme double 1668:1673 arg1 mutants 1686:1692 double and triple mutants 1668:1692 double and triple mutants 1668:1692 The increasingly strong growth-defect phenotypes in double and triple mutants suggests that the LRX proteins have similar functions and that they are important for proper plant development. 26099801 1 79 theme hydroxyproline-rich 342:360 arg1 HRGPs 377:381 HRGPs 377:381 HRGPs 377:381 BACKGROUND Leucine-rich repeat extensins (LRXs) are extracellular proteins consisting of an N-terminal leucine-rich repeat (LRR) domain and a C-terminal extensin domain containing the typical features of this class of structural hydroxyproline-rich glycoproteins (HRGPs). 26099801 1 79 theme hydroxyproline-rich 342:360 arg1 glycoproteins 362:374 structural hydroxyproline-rich glycoproteins 331:374 structural hydroxyproline-rich glycoproteins (HRGPs) 331:382 BACKGROUND Leucine-rich repeat extensins (LRXs) are extracellular proteins consisting of an N-terminal leucine-rich repeat (LRR) domain and a C-terminal extensin domain containing the typical features of this class of structural hydroxyproline-rich glycoproteins (HRGPs). 26099801 8 80 theme cell 1266:1269 arg1 composition 1276:1286 cell wall composition 1266:1286 cell wall composition 1266:1286 Analysis of cell wall composition revealed a number of changes to cell wall polysaccharides in the mutants. 26099801 4 81 theme hair 727:730 arg1 cells 732:736 non-root hair cells 718:736 non-root hair cells 718:736 The importance of LRX proteins in non-root hair cells and on the structural changes induced by mutations in LRX genes remains elusive. 26099801 7 82 theme mutations 1111:1119 arg1 effects 1100:1106 Synergistic effects 1088:1106 Synergistic effects of mutations with gradually more severe growth retardation phenotypes in double and triple mutants 1088:1205 Synergistic effects of mutations with gradually more severe growth retardation phenotypes in double and triple mutants suggest a similar function of the three genes. 26099801 8 83 theme composition 1276:1286 arg1 Analysis 1254:1261 Analysis 1254:1261 Analysis of cell wall composition 1254:1286 Analysis of cell wall composition revealed a number of changes to cell wall polysaccharides in the mutants. 26099801 2 84 theme LRR 389:391 arg1 likely 403:408 likely 403:408 likely 403:408 The LRR domain is likely to bind an interaction partner, whereas the extensin domain has an anchoring function to insolubilize the protein in the cell wall. 26099801 2 84 theme LRR 389:391 arg1 domain 393:398 The LRR domain 385:398 The LRR domain 385:398 The LRR domain is likely to bind an interaction partner, whereas the extensin domain has an anchoring function to insolubilize the protein in the cell wall. 26099801 0 85 theme leucine-rich 12:23 arg1 proteins 47:54 Arabidopsis leucine-rich repeat extensin (LRX) proteins 0:54 Arabidopsis leucine-rich repeat extensin (LRX) proteins 0:54 Arabidopsis leucine-rich repeat extensin (LRX) proteins modify cell wall composition and influence plant growth. 26099801 9 86 theme wall 1460:1463 arg1 development 1465:1475 cell wall development 1455:1475 cell wall development 1455:1475 CONCLUSIONS LRX3, LRX4, and LRX5, and most likely LRX proteins in general, are important for cell wall development. 26099801 7 87 theme genes 1247:1251 arg1 function 1225:1232 a similar function 1215:1232 a similar function of the three genes 1215:1251 Synergistic effects of mutations with gradually more severe growth retardation phenotypes in double and triple mutants suggest a similar function of the three genes. 26099801 4 88 theme LRX 702:704 arg1 proteins 706:713 LRX proteins 702:713 LRX proteins 702:713 The importance of LRX proteins in non-root hair cells and on the structural changes induced by mutations in LRX genes remains elusive. 26099801 11 89 theme proper 1780:1785 arg1 development 1793:1803 proper plant development 1780:1803 proper plant development 1780:1803 The increasingly strong growth-defect phenotypes in double and triple mutants suggests that the LRX proteins have similar functions and that they are important for proper plant development. 26099801 0 90 theme extensin 32:39 arg1 proteins 47:54 Arabidopsis leucine-rich repeat extensin (LRX) proteins 0:54 Arabidopsis leucine-rich repeat extensin (LRX) proteins 0:54 Arabidopsis leucine-rich repeat extensin (LRX) proteins modify cell wall composition and influence plant growth. 26099801 3 91 theme thaliana 620:627 arg1 LRX1 591:594 root hair-expressed LRX1 571:594 root hair-expressed LRX1 571:594 Based on the analysis of the root hair-expressed LRX1 and LRX2 of Arabidopsis thaliana, LRX proteins are important for cell wall development. 26099801 3 91 theme thaliana 620:627 arg1 LRX2 600:603 LRX2 600:603 LRX2 600:603 Based on the analysis of the root hair-expressed LRX1 and LRX2 of Arabidopsis thaliana, LRX proteins are important for cell wall development. 26099801 0 92 theme LRX 42:44 arg1 proteins 47:54 Arabidopsis leucine-rich repeat extensin (LRX) proteins 0:54 Arabidopsis leucine-rich repeat extensin (LRX) proteins 0:54 Arabidopsis leucine-rich repeat extensin (LRX) proteins modify cell wall composition and influence plant growth. 26099801 2 93 theme extensin 454:461 arg1 domain 463:468 the extensin domain 450:468 the extensin domain 450:468 The LRR domain is likely to bind an interaction partner, whereas the extensin domain has an anchoring function to insolubilize the protein in the cell wall. 26099801 2 94 contain has 470:472 arg2 function 487:494 an anchoring function 474:494 an anchoring function to insolubilize the protein in the cell wall 474:539 The LRR domain is likely to bind an interaction partner, whereas the extensin domain has an anchoring function to insolubilize the protein in the cell wall. 26099801 2 94 contain has 470:472 arg1 domain 463:468 the extensin domain 450:468 the extensin domain 450:468 The LRR domain is likely to bind an interaction partner, whereas the extensin domain has an anchoring function to insolubilize the protein in the cell wall. 26099801 10 95 from structures 1524:1533 arg1 complexity 1489:1498 the complexity 1485:1498 the complexity of changes in cell wall structures in the lrx mutants 1485:1552 Due to the complexity of changes in cell wall structures in the lrx mutants, the exact function of LRX proteins remains to be determined. 26099801 10 95 from structures 1524:1533 arg1 mutants 1546:1552 the lrx mutants 1538:1552 the lrx mutants 1538:1552 Due to the complexity of changes in cell wall structures in the lrx mutants, the exact function of LRX proteins remains to be determined. 26099801 6 96 theme cell 1050:1053 arg1 formation 1060:1068 cell wall formation 1050:1068 cell wall formation 1050:1068 The importance of these LRX genes for plant development and particularly cell wall formation was investigated. 26099801 8 97 theme wall 1325:1328 arg1 polysaccharides 1330:1344 cell wall polysaccharides 1320:1344 cell wall polysaccharides 1320:1344 Analysis of cell wall composition revealed a number of changes to cell wall polysaccharides in the mutants. 26099801 10 98 theme LRX 1577:1579 arg1 proteins 1581:1588 LRX proteins 1577:1588 LRX proteins 1577:1588 Due to the complexity of changes in cell wall structures in the lrx mutants, the exact function of LRX proteins remains to be determined. 26099801 3 99 theme LRX 630:632 arg1 proteins 634:641 LRX proteins 630:641 LRX proteins 630:641 Based on the analysis of the root hair-expressed LRX1 and LRX2 of Arabidopsis thaliana, LRX proteins are important for cell wall development. 26099801 11 100 theme similar 1730:1736 arg1 functions 1738:1746 similar functions 1730:1746 similar functions 1730:1746 The increasingly strong growth-defect phenotypes in double and triple mutants suggests that the LRX proteins have similar functions and that they are important for proper plant development. 26099801 6 101 theme plant 1015:1019 arg1 development 1021:1031 plant development 1015:1031 plant development 1015:1031 The importance of these LRX genes for plant development and particularly cell wall formation was investigated. 26099801 3 102 theme wall 666:669 arg1 development 671:681 cell wall development 661:681 cell wall development 661:681 Based on the analysis of the root hair-expressed LRX1 and LRX2 of Arabidopsis thaliana, LRX proteins are important for cell wall development. 26099801 7 103 theme Synergistic 1088:1098 arg1 effects 1100:1106 Synergistic effects 1088:1106 Synergistic effects of mutations with gradually more severe growth retardation phenotypes in double and triple mutants 1088:1205 Synergistic effects of mutations with gradually more severe growth retardation phenotypes in double and triple mutants suggest a similar function of the three genes. 26099801 8 104 from changes 1309:1315 arg1 mutants 1353:1359 the mutants 1349:1359 the mutants 1349:1359 Analysis of cell wall composition revealed a number of changes to cell wall polysaccharides in the mutants. 27838508 12 0 theme CONCLUSIONS 1861:1871 arg1 toothpaste 1902:1911 CONCLUSIONS Stannous fluoride-containing toothpaste 1861:1911 CONCLUSIONS Stannous fluoride-containing toothpaste 1861:1911 CONCLUSIONS Stannous fluoride-containing toothpaste not only showed better inhibitory effect against oral microbial biofilm, but was also able to modulate microbial composition within multi-species biofilm compared with conventional sodium fluoride-containing toothpaste. 27838508 9 1 theme CPH 1505:1507 arg1 treatments 1509:1518 CCP and CPH treatments 1497:1518 CCP and CPH treatments 1497:1518 The EPS amounts of the three-species biofilm were significantly reduced by CCP and CPH treatments, and CPH toothpaste demonstrated significant inhibition on EPS production. 27838508 1 2 theme anti-biofilm 277:288 arg1 properties 290:299 anti-biofilm properties 277:299 anti-biofilm properties 277:299 OBJECTIVES This paper aimed to compare the mode of action of a stannous fluoride-containing toothpaste with a conventional sodium fluoride-containing toothpaste on anti-biofilm properties. 27838508 3 3 theme consecutive 731:741 arg1 days 743:746 5 consecutive days 729:746 5 consecutive days 729:746 The 48h biofilms were subjected to two-minute episodes of treatment with test agents twice a day for 5 consecutive days. 27838508 4 4 dep biomass 814:820 arg1 the 810:812 the 810:812 the 810:812 Crystal violet staining and XTT assays were used to evaluate the biomass and viability of the treated biofilm. 27838508 11 5 contain had 1821:1823 arg2 effect 1835:1840 a greater effect 1825:1840 a greater effect 1825:1840 In all experiments CPH had a significantly greater effect than CCP (p<0.05) and CCP had a greater effect than PBS (p<0.05). 27838508 11 5 contain had 1821:1823 arg1 CCP 1817:1819 CCP 1817:1819 CCP 1817:1819 In all experiments CPH had a significantly greater effect than CCP (p<0.05) and CCP had a greater effect than PBS (p<0.05). 27838508 5 6 theme bacteria/extracellular 883:904 arg1 EPS 923:925 EPS 923:925 EPS 923:925 Live/dead staining and bacteria/extracellular polysaccharides (EPS) double-staining were used to visualize the biofilm structure and to quantify microbial/extracellular components of the treated biofilms. 27838508 5 6 theme bacteria/extracellular 883:904 arg1 polysaccharides 906:920 bacteria/extracellular polysaccharides 883:920 bacteria/extracellular polysaccharides (EPS) double-staining 883:942 Live/dead staining and bacteria/extracellular polysaccharides (EPS) double-staining were used to visualize the biofilm structure and to quantify microbial/extracellular components of the treated biofilms. 27838508 12 7 theme sodium 2094:2099 arg1 toothpaste 2121:2130 conventional sodium fluoride-containing toothpaste 2081:2130 conventional sodium fluoride-containing toothpaste 2081:2130 CONCLUSIONS Stannous fluoride-containing toothpaste not only showed better inhibitory effect against oral microbial biofilm, but was also able to modulate microbial composition within multi-species biofilm compared with conventional sodium fluoride-containing toothpaste. 27838508 6 8 theme biofilms 1216:1223 arg1 composition 1197:1207 microbial composition 1187:1207 microbial composition of the biofilms after treatment 1187:1239 Species-specific fluorescent in situ hybridization and quantitative polymerase chain reaction (qPCR) were used to analyze microbial composition of the biofilms after treatment. 27838508 2 9 theme three-species 312:324 arg1 model 334:338 A three-species biofilm model 310:338 METHODS A three-species biofilm model that consists of Streptococcus mutans, Streptococcus sanguinis and Porphyromonas gingivalis 302:430 METHODS A three-species biofilm model that consists of Streptococcus mutans, Streptococcus sanguinis and Porphyromonas gingivalis was established to compare the anti-biofilm properties of a stannous fluoride-containing toothpaste (CPH), a conventional sodium fluoride-containing toothpaste (CCP) and a negative control (PBS). 27838508 1 10 theme stannous 176:183 arg1 toothpaste 205:214 a stannous fluoride-containing toothpaste 174:214 a stannous fluoride-containing toothpaste 174:214 OBJECTIVES This paper aimed to compare the mode of action of a stannous fluoride-containing toothpaste with a conventional sodium fluoride-containing toothpaste on anti-biofilm properties. 27838508 1 11 from toothpaste 263:272 arg1 properties 290:299 anti-biofilm properties 277:299 anti-biofilm properties 277:299 OBJECTIVES This paper aimed to compare the mode of action of a stannous fluoride-containing toothpaste with a conventional sodium fluoride-containing toothpaste on anti-biofilm properties. 27838508 3 12 theme 48h 632:634 arg1 biofilms 636:643 The 48h biofilms 628:643 The 48h biofilms 628:643 The 48h biofilms were subjected to two-minute episodes of treatment with test agents twice a day for 5 consecutive days. 27838508 9 13 theme EPS 1579:1581 arg1 production 1583:1592 EPS production 1579:1592 EPS production 1579:1592 The EPS amounts of the three-species biofilm were significantly reduced by CCP and CPH treatments, and CPH toothpaste demonstrated significant inhibition on EPS production. 27838508 6 14 used used 1171:1174 arg2 qPCR 1160:1163 qPCR 1160:1163 qPCR 1160:1163 Species-specific fluorescent in situ hybridization and quantitative polymerase chain reaction (qPCR) were used to analyze microbial composition of the biofilms after treatment. 27838508 6 14 used used 1171:1174 arg2 hybridization 1102:1114 Species-specific fluorescent in situ hybridization 1065:1114 Species-specific fluorescent in situ hybridization 1065:1114 Species-specific fluorescent in situ hybridization and quantitative polymerase chain reaction (qPCR) were used to analyze microbial composition of the biofilms after treatment. 27838508 6 14 used used 1171:1174 arg2 reaction 1150:1157 quantitative polymerase chain reaction 1120:1157 quantitative polymerase chain reaction (qPCR) 1120:1164 Species-specific fluorescent in situ hybridization and quantitative polymerase chain reaction (qPCR) were used to analyze microbial composition of the biofilms after treatment. 27838508 2 15 theme control 613:619 arg1 properties 476:485 the anti-biofilm properties 459:485 the anti-biofilm properties of a stannous fluoride-containing toothpaste (CPH), a conventional sodium fluoride-containing toothpaste (CCP) and a negative control (PBS) 459:625 METHODS A three-species biofilm model that consists of Streptococcus mutans, Streptococcus sanguinis and Porphyromonas gingivalis was established to compare the anti-biofilm properties of a stannous fluoride-containing toothpaste (CPH), a conventional sodium fluoride-containing toothpaste (CCP) and a negative control (PBS). 27838508 4 16 theme Crystal 749:755 arg1 staining 764:771 Crystal violet staining 749:771 Crystal violet staining 749:771 Crystal violet staining and XTT assays were used to evaluate the biomass and viability of the treated biofilm. 27838508 11 17 theme greater 1827:1833 arg1 effect 1835:1840 a greater effect 1825:1840 a greater effect 1825:1840 In all experiments CPH had a significantly greater effect than CCP (p<0.05) and CCP had a greater effect than PBS (p<0.05). 27838508 6 18 theme in 1094:1095 arg1 hybridization 1102:1114 Species-specific fluorescent in situ hybridization 1065:1114 Species-specific fluorescent in situ hybridization 1065:1114 Species-specific fluorescent in situ hybridization and quantitative polymerase chain reaction (qPCR) were used to analyze microbial composition of the biofilms after treatment. 27838508 2 19 theme conventional 541:552 arg1 CCP 593:595 CCP 593:595 CCP 593:595 METHODS A three-species biofilm model that consists of Streptococcus mutans, Streptococcus sanguinis and Porphyromonas gingivalis was established to compare the anti-biofilm properties of a stannous fluoride-containing toothpaste (CPH), a conventional sodium fluoride-containing toothpaste (CCP) and a negative control (PBS). 27838508 2 19 theme conventional 541:552 arg1 toothpaste 581:590 a conventional sodium fluoride-containing toothpaste 539:590 a conventional sodium fluoride-containing toothpaste (CCP) 539:596 METHODS A three-species biofilm model that consists of Streptococcus mutans, Streptococcus sanguinis and Porphyromonas gingivalis was established to compare the anti-biofilm properties of a stannous fluoride-containing toothpaste (CPH), a conventional sodium fluoride-containing toothpaste (CCP) and a negative control (PBS). 27838508 8 20 theme live/dead 1402:1410 arg1 staining 1412:1419 the live/dead staining 1398:1419 the live/dead staining 1398:1419 The inhibitory effect was further confirmed by the live/dead staining. 27838508 5 21 used used 949:952 arg2 staining 870:877 Live/dead staining 860:877 Live/dead staining 860:877 Live/dead staining and bacteria/extracellular polysaccharides (EPS) double-staining were used to visualize the biofilm structure and to quantify microbial/extracellular components of the treated biofilms. 27838508 5 21 used used 949:952 arg2 double-staining 928:942 bacteria/extracellular polysaccharides (EPS) double-staining 883:942 bacteria/extracellular polysaccharides (EPS) double-staining 883:942 Live/dead staining and bacteria/extracellular polysaccharides (EPS) double-staining were used to visualize the biofilm structure and to quantify microbial/extracellular components of the treated biofilms. 27838508 6 22 theme Species-specific 1065:1080 arg1 hybridization 1102:1114 Species-specific fluorescent in situ hybridization 1065:1114 Species-specific fluorescent in situ hybridization 1065:1114 Species-specific fluorescent in situ hybridization and quantitative polymerase chain reaction (qPCR) were used to analyze microbial composition of the biofilms after treatment. 27838508 0 23 theme fluoride 66:73 arg1 effect 12:17 Comparative effect 0:17 Comparative effect of a stannous fluoride toothpaste and a sodium fluoride 0:73 Comparative effect of a stannous fluoride toothpaste and a sodium fluoride toothpaste on a multispecies biofilm. 27838508 5 24 theme microbial/extracellular 1005:1027 arg1 components 1029:1038 microbial/extracellular components 1005:1038 microbial/extracellular components of the treated biofilms 1005:1062 Live/dead staining and bacteria/extracellular polysaccharides (EPS) double-staining were used to visualize the biofilm structure and to quantify microbial/extracellular components of the treated biofilms. 27838508 2 25 theme fluoride-containing 561:579 arg1 CCP 593:595 CCP 593:595 CCP 593:595 METHODS A three-species biofilm model that consists of Streptococcus mutans, Streptococcus sanguinis and Porphyromonas gingivalis was established to compare the anti-biofilm properties of a stannous fluoride-containing toothpaste (CPH), a conventional sodium fluoride-containing toothpaste (CCP) and a negative control (PBS). 27838508 2 25 theme fluoride-containing 561:579 arg1 toothpaste 581:590 a conventional sodium fluoride-containing toothpaste 539:590 a conventional sodium fluoride-containing toothpaste (CCP) 539:596 METHODS A three-species biofilm model that consists of Streptococcus mutans, Streptococcus sanguinis and Porphyromonas gingivalis was established to compare the anti-biofilm properties of a stannous fluoride-containing toothpaste (CPH), a conventional sodium fluoride-containing toothpaste (CCP) and a negative control (PBS). 27838508 0 26 theme multispecies 91:102 arg1 biofilm 104:110 a multispecies biofilm 89:110 a multispecies biofilm 89:110 Comparative effect of a stannous fluoride toothpaste and a sodium fluoride toothpaste on a multispecies biofilm. 27838508 2 27 theme stannous 492:499 arg1 toothpaste 521:530 a stannous fluoride-containing toothpaste 490:530 a stannous fluoride-containing toothpaste (CPH) 490:536 METHODS A three-species biofilm model that consists of Streptococcus mutans, Streptococcus sanguinis and Porphyromonas gingivalis was established to compare the anti-biofilm properties of a stannous fluoride-containing toothpaste (CPH), a conventional sodium fluoride-containing toothpaste (CCP) and a negative control (PBS). 27838508 2 27 theme stannous 492:499 arg1 CPH 533:535 CPH 533:535 CPH 533:535 METHODS A three-species biofilm model that consists of Streptococcus mutans, Streptococcus sanguinis and Porphyromonas gingivalis was established to compare the anti-biofilm properties of a stannous fluoride-containing toothpaste (CPH), a conventional sodium fluoride-containing toothpaste (CCP) and a negative control (PBS). 27838508 6 28 dep in 1094:1095 arg1 situ 1097:1100 situ 1097:1100 situ 1097:1100 Species-specific fluorescent in situ hybridization and quantitative polymerase chain reaction (qPCR) were used to analyze microbial composition of the biofilms after treatment. 27838508 0 29 theme Comparative 0:10 arg1 effect 12:17 Comparative effect 0:17 Comparative effect of a stannous fluoride toothpaste and a sodium fluoride 0:73 Comparative effect of a stannous fluoride toothpaste and a sodium fluoride toothpaste on a multispecies biofilm. 27838508 6 30 theme chain 1144:1148 arg1 reaction 1150:1157 quantitative polymerase chain reaction 1120:1157 quantitative polymerase chain reaction (qPCR) 1120:1164 Species-specific fluorescent in situ hybridization and quantitative polymerase chain reaction (qPCR) were used to analyze microbial composition of the biofilms after treatment. 27838508 6 30 theme chain 1144:1148 arg1 qPCR 1160:1163 qPCR 1160:1163 qPCR 1160:1163 Species-specific fluorescent in situ hybridization and quantitative polymerase chain reaction (qPCR) were used to analyze microbial composition of the biofilms after treatment. 27838508 4 31 theme XTT 777:779 arg1 assays 781:786 XTT assays 777:786 XTT assays 777:786 Crystal violet staining and XTT assays were used to evaluate the biomass and viability of the treated biofilm. 27838508 2 32 theme anti-biofilm 463:474 arg1 properties 476:485 the anti-biofilm properties 459:485 the anti-biofilm properties of a stannous fluoride-containing toothpaste (CPH), a conventional sodium fluoride-containing toothpaste (CCP) and a negative control (PBS) 459:625 METHODS A three-species biofilm model that consists of Streptococcus mutans, Streptococcus sanguinis and Porphyromonas gingivalis was established to compare the anti-biofilm properties of a stannous fluoride-containing toothpaste (CPH), a conventional sodium fluoride-containing toothpaste (CCP) and a negative control (PBS). 27838508 6 33 theme quantitative 1120:1131 arg1 reaction 1150:1157 quantitative polymerase chain reaction 1120:1157 quantitative polymerase chain reaction (qPCR) 1120:1164 Species-specific fluorescent in situ hybridization and quantitative polymerase chain reaction (qPCR) were used to analyze microbial composition of the biofilms after treatment. 27838508 6 33 theme quantitative 1120:1131 arg1 qPCR 1160:1163 qPCR 1160:1163 qPCR 1160:1163 Species-specific fluorescent in situ hybridization and quantitative polymerase chain reaction (qPCR) were used to analyze microbial composition of the biofilms after treatment. 27838508 3 34 theme treatment 686:694 arg1 episodes 674:681 two-minute episodes 663:681 two-minute episodes of treatment with test agents 663:711 The 48h biofilms were subjected to two-minute episodes of treatment with test agents twice a day for 5 consecutive days. 27838508 0 35 theme stannous 24:31 arg1 fluoride 33:40 a stannous fluoride toothpaste and a sodium fluoride 22:73 fluoride 33:40 Comparative effect of a stannous fluoride toothpaste and a sodium fluoride toothpaste on a multispecies biofilm. 27838508 12 36 theme microbial 1967:1975 arg1 biofilm 1977:1983 oral microbial biofilm 1962:1983 oral microbial biofilm 1962:1983 CONCLUSIONS Stannous fluoride-containing toothpaste not only showed better inhibitory effect against oral microbial biofilm, but was also able to modulate microbial composition within multi-species biofilm compared with conventional sodium fluoride-containing toothpaste. 27838508 2 37 theme toothpaste 521:530 arg1 properties 476:485 the anti-biofilm properties 459:485 the anti-biofilm properties of a stannous fluoride-containing toothpaste (CPH), a conventional sodium fluoride-containing toothpaste (CCP) and a negative control (PBS) 459:625 METHODS A three-species biofilm model that consists of Streptococcus mutans, Streptococcus sanguinis and Porphyromonas gingivalis was established to compare the anti-biofilm properties of a stannous fluoride-containing toothpaste (CPH), a conventional sodium fluoride-containing toothpaste (CCP) and a negative control (PBS). 27838508 4 38 theme treated 843:849 arg1 biofilm 851:857 the treated biofilm 839:857 the treated biofilm 839:857 Crystal violet staining and XTT assays were used to evaluate the biomass and viability of the treated biofilm. 27838508 9 39 theme biofilm 1459:1465 arg1 amounts 1430:1436 The EPS amounts 1422:1436 The EPS amounts of the three-species biofilm 1422:1465 The EPS amounts of the three-species biofilm were significantly reduced by CCP and CPH treatments, and CPH toothpaste demonstrated significant inhibition on EPS production. 27838508 9 39 theme biofilm 1459:1465 arg1 biofilm 1459:1465 the three-species biofilm 1441:1465 the three-species biofilm 1441:1465 The EPS amounts of the three-species biofilm were significantly reduced by CCP and CPH treatments, and CPH toothpaste demonstrated significant inhibition on EPS production. 27838508 10 40 theme CPH 1613:1615 arg1 toothpaste 1617:1626 CPH toothpaste 1613:1626 CPH toothpaste 1613:1626 More importantly, CPH toothpaste significantly suppressed S. mutans and P. gingvalis, and enriched S. sanguinis in the three-species biofilm. 27838508 12 41 theme inhibitory 1936:1945 arg1 effect 1947:1952 better inhibitory effect 1929:1952 better inhibitory effect 1929:1952 CONCLUSIONS Stannous fluoride-containing toothpaste not only showed better inhibitory effect against oral microbial biofilm, but was also able to modulate microbial composition within multi-species biofilm compared with conventional sodium fluoride-containing toothpaste. 27838508 5 42 theme treated 1047:1053 arg1 biofilms 1055:1062 the treated biofilms 1043:1062 the treated biofilms 1043:1062 Live/dead staining and bacteria/extracellular polysaccharides (EPS) double-staining were used to visualize the biofilm structure and to quantify microbial/extracellular components of the treated biofilms. 27838508 3 43 theme test 701:704 arg1 agents 706:711 test agents 701:711 test agents 701:711 The 48h biofilms were subjected to two-minute episodes of treatment with test agents twice a day for 5 consecutive days. 27838508 9 44 theme CPH 1525:1527 arg1 toothpaste 1529:1538 CPH toothpaste 1525:1538 CPH toothpaste 1525:1538 The EPS amounts of the three-species biofilm were significantly reduced by CCP and CPH treatments, and CPH toothpaste demonstrated significant inhibition on EPS production. 27838508 1 45 theme conventional 223:234 arg1 toothpaste 263:272 a conventional sodium fluoride-containing toothpaste 221:272 a conventional sodium fluoride-containing toothpaste on anti-biofilm properties 221:299 OBJECTIVES This paper aimed to compare the mode of action of a stannous fluoride-containing toothpaste with a conventional sodium fluoride-containing toothpaste on anti-biofilm properties. 27838508 12 46 theme Stannous 1873:1880 arg1 toothpaste 1902:1911 CONCLUSIONS Stannous fluoride-containing toothpaste 1861:1911 CONCLUSIONS Stannous fluoride-containing toothpaste 1861:1911 CONCLUSIONS Stannous fluoride-containing toothpaste not only showed better inhibitory effect against oral microbial biofilm, but was also able to modulate microbial composition within multi-species biofilm compared with conventional sodium fluoride-containing toothpaste. 27838508 1 47 theme fluoride-containing 243:261 arg1 toothpaste 263:272 a conventional sodium fluoride-containing toothpaste 221:272 a conventional sodium fluoride-containing toothpaste on anti-biofilm properties 221:299 OBJECTIVES This paper aimed to compare the mode of action of a stannous fluoride-containing toothpaste with a conventional sodium fluoride-containing toothpaste on anti-biofilm properties. 27838508 7 48 theme CPH 1325:1327 arg1 treatment 1340:1348 CPH toothpaste treatment 1325:1348 CPH toothpaste treatment 1325:1348 RESULTS The biomass and viability of the biofilms were significantly reduced after CPH toothpaste treatment. 27838508 12 49 theme fluoride-containing 2101:2119 arg1 toothpaste 2121:2130 conventional sodium fluoride-containing toothpaste 2081:2130 conventional sodium fluoride-containing toothpaste 2081:2130 CONCLUSIONS Stannous fluoride-containing toothpaste not only showed better inhibitory effect against oral microbial biofilm, but was also able to modulate microbial composition within multi-species biofilm compared with conventional sodium fluoride-containing toothpaste. 27838508 11 50 theme greater 1780:1786 arg1 effect 1788:1793 a significantly greater effect 1764:1793 a significantly greater effect 1764:1793 In all experiments CPH had a significantly greater effect than CCP (p<0.05) and CCP had a greater effect than PBS (p<0.05). 27838508 1 51 theme action 164:169 arg1 mode 156:159 the mode 152:159 the mode of action of a stannous fluoride-containing toothpaste with a conventional sodium fluoride-containing toothpaste on anti-biofilm properties 152:299 OBJECTIVES This paper aimed to compare the mode of action of a stannous fluoride-containing toothpaste with a conventional sodium fluoride-containing toothpaste on anti-biofilm properties. 27838508 4 52 theme biofilm 851:857 arg1 biomass 814:820 biomass 814:820 biomass 814:820 Crystal violet staining and XTT assays were used to evaluate the biomass and viability of the treated biofilm. 27838508 4 52 theme biofilm 851:857 arg1 viability 826:834 viability 826:834 viability 826:834 Crystal violet staining and XTT assays were used to evaluate the biomass and viability of the treated biofilm. 27838508 5 53 theme polysaccharides 906:920 arg1 double-staining 928:942 bacteria/extracellular polysaccharides (EPS) double-staining 883:942 bacteria/extracellular polysaccharides (EPS) double-staining 883:942 Live/dead staining and bacteria/extracellular polysaccharides (EPS) double-staining were used to visualize the biofilm structure and to quantify microbial/extracellular components of the treated biofilms. 27838508 2 54 theme biofilm 326:332 arg1 model 334:338 A three-species biofilm model 310:338 METHODS A three-species biofilm model that consists of Streptococcus mutans, Streptococcus sanguinis and Porphyromonas gingivalis 302:430 METHODS A three-species biofilm model that consists of Streptococcus mutans, Streptococcus sanguinis and Porphyromonas gingivalis was established to compare the anti-biofilm properties of a stannous fluoride-containing toothpaste (CPH), a conventional sodium fluoride-containing toothpaste (CCP) and a negative control (PBS). 27838508 9 55 theme significant 1553:1563 arg1 inhibition 1565:1574 significant inhibition 1553:1574 significant inhibition on EPS production 1553:1592 The EPS amounts of the three-species biofilm were significantly reduced by CCP and CPH treatments, and CPH toothpaste demonstrated significant inhibition on EPS production. 27838508 12 56 theme conventional 2081:2092 arg1 toothpaste 2121:2130 conventional sodium fluoride-containing toothpaste 2081:2130 conventional sodium fluoride-containing toothpaste 2081:2130 CONCLUSIONS Stannous fluoride-containing toothpaste not only showed better inhibitory effect against oral microbial biofilm, but was also able to modulate microbial composition within multi-species biofilm compared with conventional sodium fluoride-containing toothpaste. 27838508 3 57 with treatment 686:694 arg1 agents 706:711 test agents 701:711 test agents 701:711 The 48h biofilms were subjected to two-minute episodes of treatment with test agents twice a day for 5 consecutive days. 27838508 5 58 theme Live/dead 860:868 arg1 staining 870:877 Live/dead staining 860:877 Live/dead staining 860:877 Live/dead staining and bacteria/extracellular polysaccharides (EPS) double-staining were used to visualize the biofilm structure and to quantify microbial/extracellular components of the treated biofilms. 27838508 8 59 theme inhibitory 1355:1364 arg1 effect 1366:1371 The inhibitory effect 1351:1371 The inhibitory effect 1351:1371 The inhibitory effect was further confirmed by the live/dead staining. 27838508 10 60 theme three-species 1714:1726 arg1 biofilm 1728:1734 the three-species biofilm 1710:1734 the three-species biofilm 1710:1734 More importantly, CPH toothpaste significantly suppressed S. mutans and P. gingvalis, and enriched S. sanguinis in the three-species biofilm. 27838508 12 61 theme multi-species 2045:2057 arg1 biofilm 2059:2065 multi-species biofilm 2045:2065 multi-species biofilm compared with conventional sodium fluoride-containing toothpaste 2045:2130 CONCLUSIONS Stannous fluoride-containing toothpaste not only showed better inhibitory effect against oral microbial biofilm, but was also able to modulate microbial composition within multi-species biofilm compared with conventional sodium fluoride-containing toothpaste. 27838508 2 62 theme negative 604:611 arg1 control 613:619 a negative control 602:619 a negative control (PBS) 602:625 METHODS A three-species biofilm model that consists of Streptococcus mutans, Streptococcus sanguinis and Porphyromonas gingivalis was established to compare the anti-biofilm properties of a stannous fluoride-containing toothpaste (CPH), a conventional sodium fluoride-containing toothpaste (CCP) and a negative control (PBS). 27838508 2 62 theme negative 604:611 arg1 PBS 622:624 PBS 622:624 PBS 622:624 METHODS A three-species biofilm model that consists of Streptococcus mutans, Streptococcus sanguinis and Porphyromonas gingivalis was established to compare the anti-biofilm properties of a stannous fluoride-containing toothpaste (CPH), a conventional sodium fluoride-containing toothpaste (CCP) and a negative control (PBS). 27838508 0 63 theme sodium 59:64 arg1 fluoride 66:73 a sodium fluoride 57:73 a sodium fluoride 57:73 Comparative effect of a stannous fluoride toothpaste and a sodium fluoride toothpaste on a multispecies biofilm. 27838508 6 64 theme fluorescent 1082:1092 arg1 hybridization 1102:1114 Species-specific fluorescent in situ hybridization 1065:1114 Species-specific fluorescent in situ hybridization 1065:1114 Species-specific fluorescent in situ hybridization and quantitative polymerase chain reaction (qPCR) were used to analyze microbial composition of the biofilms after treatment. 27838508 7 65 theme biofilms 1283:1290 arg1 viability 1266:1274 viability 1266:1274 viability 1266:1274 RESULTS The biomass and viability of the biofilms were significantly reduced after CPH toothpaste treatment. 27838508 7 65 theme biofilms 1283:1290 arg1 biomass 1254:1260 biomass 1254:1260 biomass 1254:1260 RESULTS The biomass and viability of the biofilms were significantly reduced after CPH toothpaste treatment. 27838508 7 66 dep RESULTS 1242:1248 arg1 reduced 1311:1317 reduced 1311:1317 were significantly reduced after CPH toothpaste treatment 1292:1348 RESULTS The biomass and viability of the biofilms were significantly reduced after CPH toothpaste treatment. 27838508 2 67 dep METHODS 302:308 arg1 model 334:338 A three-species biofilm model 310:338 METHODS A three-species biofilm model that consists of Streptococcus mutans, Streptococcus sanguinis and Porphyromonas gingivalis 302:430 METHODS A three-species biofilm model that consists of Streptococcus mutans, Streptococcus sanguinis and Porphyromonas gingivalis was established to compare the anti-biofilm properties of a stannous fluoride-containing toothpaste (CPH), a conventional sodium fluoride-containing toothpaste (CCP) and a negative control (PBS). 27838508 12 68 theme microbial 2016:2024 arg1 composition 2026:2036 microbial composition 2016:2036 microbial composition 2016:2036 CONCLUSIONS Stannous fluoride-containing toothpaste not only showed better inhibitory effect against oral microbial biofilm, but was also able to modulate microbial composition within multi-species biofilm compared with conventional sodium fluoride-containing toothpaste. 27838508 2 69 theme toothpaste 581:590 arg1 properties 476:485 the anti-biofilm properties 459:485 the anti-biofilm properties of a stannous fluoride-containing toothpaste (CPH), a conventional sodium fluoride-containing toothpaste (CCP) and a negative control (PBS) 459:625 METHODS A three-species biofilm model that consists of Streptococcus mutans, Streptococcus sanguinis and Porphyromonas gingivalis was established to compare the anti-biofilm properties of a stannous fluoride-containing toothpaste (CPH), a conventional sodium fluoride-containing toothpaste (CCP) and a negative control (PBS). 27838508 7 70 dep biomass 1254:1260 arg1 The 1250:1252 The 1250:1252 The 1250:1252 RESULTS The biomass and viability of the biofilms were significantly reduced after CPH toothpaste treatment. 27838508 11 71 contain had 1760:1762 arg2 effect 1788:1793 a significantly greater effect 1764:1793 a significantly greater effect 1764:1793 In all experiments CPH had a significantly greater effect than CCP (p<0.05) and CCP had a greater effect than PBS (p<0.05). 27838508 11 71 contain had 1760:1762 arg1 CPH 1756:1758 CPH 1756:1758 CPH 1756:1758 In all experiments CPH had a significantly greater effect than CCP (p<0.05) and CCP had a greater effect than PBS (p<0.05). 27838508 2 72 theme sodium 554:559 arg1 CCP 593:595 CCP 593:595 CCP 593:595 METHODS A three-species biofilm model that consists of Streptococcus mutans, Streptococcus sanguinis and Porphyromonas gingivalis was established to compare the anti-biofilm properties of a stannous fluoride-containing toothpaste (CPH), a conventional sodium fluoride-containing toothpaste (CCP) and a negative control (PBS). 27838508 2 72 theme sodium 554:559 arg1 toothpaste 581:590 a conventional sodium fluoride-containing toothpaste 539:590 a conventional sodium fluoride-containing toothpaste (CCP) 539:596 METHODS A three-species biofilm model that consists of Streptococcus mutans, Streptococcus sanguinis and Porphyromonas gingivalis was established to compare the anti-biofilm properties of a stannous fluoride-containing toothpaste (CPH), a conventional sodium fluoride-containing toothpaste (CCP) and a negative control (PBS). 27838508 1 73 dep OBJECTIVES 113:122 arg1 aimed 135:139 aimed 135:139 aimed to compare the mode of action of a stannous fluoride-containing toothpaste with a conventional sodium fluoride-containing toothpaste on anti-biofilm properties 135:299 OBJECTIVES This paper aimed to compare the mode of action of a stannous fluoride-containing toothpaste with a conventional sodium fluoride-containing toothpaste on anti-biofilm properties. 27838508 5 74 theme biofilm 971:977 arg1 structure 979:987 the biofilm structure 967:987 the biofilm structure 967:987 Live/dead staining and bacteria/extracellular polysaccharides (EPS) double-staining were used to visualize the biofilm structure and to quantify microbial/extracellular components of the treated biofilms. 27838508 4 75 theme violet 757:762 arg1 staining 764:771 Crystal violet staining 749:771 Crystal violet staining 749:771 Crystal violet staining and XTT assays were used to evaluate the biomass and viability of the treated biofilm. 27838508 2 76 theme Porphyromonas 407:419 arg1 gingivalis 421:430 Porphyromonas gingivalis 407:430 Porphyromonas gingivalis 407:430 METHODS A three-species biofilm model that consists of Streptococcus mutans, Streptococcus sanguinis and Porphyromonas gingivalis was established to compare the anti-biofilm properties of a stannous fluoride-containing toothpaste (CPH), a conventional sodium fluoride-containing toothpaste (CCP) and a negative control (PBS). 27838508 9 77 theme EPS 1426:1428 arg1 amounts 1430:1436 The EPS amounts 1422:1436 The EPS amounts of the three-species biofilm 1422:1465 The EPS amounts of the three-species biofilm were significantly reduced by CCP and CPH treatments, and CPH toothpaste demonstrated significant inhibition on EPS production. 27838508 9 77 theme EPS 1426:1428 arg1 biofilm 1459:1465 the three-species biofilm 1441:1465 the three-species biofilm 1441:1465 The EPS amounts of the three-species biofilm were significantly reduced by CCP and CPH treatments, and CPH toothpaste demonstrated significant inhibition on EPS production. 27838508 12 78 theme oral 1962:1965 arg1 biofilm 1977:1983 oral microbial biofilm 1962:1983 oral microbial biofilm 1962:1983 CONCLUSIONS Stannous fluoride-containing toothpaste not only showed better inhibitory effect against oral microbial biofilm, but was also able to modulate microbial composition within multi-species biofilm compared with conventional sodium fluoride-containing toothpaste. 27838508 6 79 theme polymerase 1133:1142 arg1 reaction 1150:1157 quantitative polymerase chain reaction 1120:1157 quantitative polymerase chain reaction (qPCR) 1120:1164 Species-specific fluorescent in situ hybridization and quantitative polymerase chain reaction (qPCR) were used to analyze microbial composition of the biofilms after treatment. 27838508 6 79 theme polymerase 1133:1142 arg1 qPCR 1160:1163 qPCR 1160:1163 qPCR 1160:1163 Species-specific fluorescent in situ hybridization and quantitative polymerase chain reaction (qPCR) were used to analyze microbial composition of the biofilms after treatment. 27838508 0 80 theme fluoride 33:40 arg1 effect 12:17 Comparative effect 0:17 Comparative effect of a stannous fluoride toothpaste and a sodium fluoride 0:73 Comparative effect of a stannous fluoride toothpaste and a sodium fluoride toothpaste on a multispecies biofilm. 27838508 1 81 theme fluoride-containing 185:203 arg1 toothpaste 205:214 a stannous fluoride-containing toothpaste 174:214 a stannous fluoride-containing toothpaste 174:214 OBJECTIVES This paper aimed to compare the mode of action of a stannous fluoride-containing toothpaste with a conventional sodium fluoride-containing toothpaste on anti-biofilm properties. 27838508 3 82 theme two-minute 663:672 arg1 episodes 674:681 two-minute episodes 663:681 two-minute episodes of treatment with test agents 663:711 The 48h biofilms were subjected to two-minute episodes of treatment with test agents twice a day for 5 consecutive days. 27838508 9 83 theme three-species 1445:1457 arg1 biofilm 1459:1465 the three-species biofilm 1441:1465 the three-species biofilm 1441:1465 The EPS amounts of the three-species biofilm were significantly reduced by CCP and CPH treatments, and CPH toothpaste demonstrated significant inhibition on EPS production. 27838508 12 84 theme better 1929:1934 arg1 effect 1947:1952 better inhibitory effect 1929:1952 better inhibitory effect 1929:1952 CONCLUSIONS Stannous fluoride-containing toothpaste not only showed better inhibitory effect against oral microbial biofilm, but was also able to modulate microbial composition within multi-species biofilm compared with conventional sodium fluoride-containing toothpaste. 27838508 0 85 dep fluoride 33:40 arg1 toothpaste 42:51 toothpaste 42:51 toothpaste 42:51 Comparative effect of a stannous fluoride toothpaste and a sodium fluoride toothpaste on a multispecies biofilm. 27838508 12 86 theme fluoride-containing 1882:1900 arg1 toothpaste 1902:1911 CONCLUSIONS Stannous fluoride-containing toothpaste 1861:1911 CONCLUSIONS Stannous fluoride-containing toothpaste 1861:1911 CONCLUSIONS Stannous fluoride-containing toothpaste not only showed better inhibitory effect against oral microbial biofilm, but was also able to modulate microbial composition within multi-species biofilm compared with conventional sodium fluoride-containing toothpaste. 27838508 2 87 theme fluoride-containing 501:519 arg1 toothpaste 521:530 a stannous fluoride-containing toothpaste 490:530 a stannous fluoride-containing toothpaste (CPH) 490:536 METHODS A three-species biofilm model that consists of Streptococcus mutans, Streptococcus sanguinis and Porphyromonas gingivalis was established to compare the anti-biofilm properties of a stannous fluoride-containing toothpaste (CPH), a conventional sodium fluoride-containing toothpaste (CCP) and a negative control (PBS). 27838508 2 87 theme fluoride-containing 501:519 arg1 CPH 533:535 CPH 533:535 CPH 533:535 METHODS A three-species biofilm model that consists of Streptococcus mutans, Streptococcus sanguinis and Porphyromonas gingivalis was established to compare the anti-biofilm properties of a stannous fluoride-containing toothpaste (CPH), a conventional sodium fluoride-containing toothpaste (CCP) and a negative control (PBS). 27838508 4 88 used used 793:796 arg2 assays 781:786 XTT assays 777:786 XTT assays 777:786 Crystal violet staining and XTT assays were used to evaluate the biomass and viability of the treated biofilm. 27838508 4 88 used used 793:796 arg2 staining 764:771 Crystal violet staining 749:771 Crystal violet staining 749:771 Crystal violet staining and XTT assays were used to evaluate the biomass and viability of the treated biofilm. 27838508 1 89 with mode 156:159 arg1 toothpaste 263:272 a conventional sodium fluoride-containing toothpaste 221:272 a conventional sodium fluoride-containing toothpaste on anti-biofilm properties 221:299 OBJECTIVES This paper aimed to compare the mode of action of a stannous fluoride-containing toothpaste with a conventional sodium fluoride-containing toothpaste on anti-biofilm properties. 27838508 9 90 from inhibition 1565:1574 arg1 production 1583:1592 EPS production 1579:1592 EPS production 1579:1592 The EPS amounts of the three-species biofilm were significantly reduced by CCP and CPH treatments, and CPH toothpaste demonstrated significant inhibition on EPS production. 27838508 6 91 theme microbial 1187:1195 arg1 composition 1197:1207 microbial composition 1187:1207 microbial composition of the biofilms after treatment 1187:1239 Species-specific fluorescent in situ hybridization and quantitative polymerase chain reaction (qPCR) were used to analyze microbial composition of the biofilms after treatment. 27838508 1 92 theme toothpaste 205:214 arg1 action 164:169 action 164:169 action of a stannous fluoride-containing toothpaste 164:214 OBJECTIVES This paper aimed to compare the mode of action of a stannous fluoride-containing toothpaste with a conventional sodium fluoride-containing toothpaste on anti-biofilm properties. 27838508 5 93 theme biofilms 1055:1062 arg1 components 1029:1038 microbial/extracellular components 1005:1038 microbial/extracellular components of the treated biofilms 1005:1062 Live/dead staining and bacteria/extracellular polysaccharides (EPS) double-staining were used to visualize the biofilm structure and to quantify microbial/extracellular components of the treated biofilms. 27838508 7 94 theme toothpaste 1329:1338 arg1 treatment 1340:1348 CPH toothpaste treatment 1325:1348 CPH toothpaste treatment 1325:1348 RESULTS The biomass and viability of the biofilms were significantly reduced after CPH toothpaste treatment. 27838508 1 95 theme sodium 236:241 arg1 toothpaste 263:272 a conventional sodium fluoride-containing toothpaste 221:272 a conventional sodium fluoride-containing toothpaste on anti-biofilm properties 221:299 OBJECTIVES This paper aimed to compare the mode of action of a stannous fluoride-containing toothpaste with a conventional sodium fluoride-containing toothpaste on anti-biofilm properties. 27838508 9 96 theme CCP 1497:1499 arg1 treatments 1509:1518 CCP and CPH treatments 1497:1518 CCP and CPH treatments 1497:1518 The EPS amounts of the three-species biofilm were significantly reduced by CCP and CPH treatments, and CPH toothpaste demonstrated significant inhibition on EPS production. 29213312 2 0 theme valuable 663:670 arg1 insights 672:679 valuable insights 663:679 valuable insights into CBP 663:688 However, limited research has integrated CBP with real pretreated biomass, and understanding how pretreatment impacts subsequent deconstruction by CBP vs. fungal enzymes can provide valuable insights into CBP and suggest other novel biomass deconstruction strategies. 29213312 3 1 theme fungal 1048:1053 arg1 enzymes 1055:1061 fungal enzymes 1048:1061 fungal enzymes 1048:1061 This study focused on determining the effect of pretreatment by dilute sulfuric acid alone (DA) and with tetrahydrofuran (THF) addition via co-solvent-enhanced lignocellulosic fractionation (CELF) on deconstruction of corn stover and Populus with much different recalcitrance by C. thermocellum vs. fungal enzymes and changes in pretreated biomass related to these differences. 29213312 9 2 theme Composition 2236:2246 arg1 measurements 2248:2259 Composition measurements 2236:2259 Composition measurements 2236:2259 Composition measurements, material balances, cellulase adsorption, and CSLM and TEM imaging revealed adding THF enhanced the enzyme accessibility, cell wall fractures, and cellular dislocation and cell wall delamination. 29213312 5 3 theme viable 1515:1520 arg1 loadings 1529:1536 viable enzyme loadings 1515:1536 viable enzyme loadings 1515:1536 These results were better than those from the conventional DA followed by either CBP or fungal enzymes or CELF followed by fungal enzyme hydrolysis, especially at viable enzyme loadings. 29213312 4 4 theme Coupling 1135:1142 arg1 fractionation 1149:1161 Coupling CELF fractionation 1135:1161 Coupling CELF fractionation of corn stover and Populus with subsequent CBP by the anaerobe C. thermocellum 1135:1240 RESULTS Coupling CELF fractionation of corn stover and Populus with subsequent CBP by the anaerobe C. thermocellum completely solubilized polysaccharides left in the pretreated solids within only 48 h without adding enzymes. 29213312 7 5 theme cell 1889:1892 arg1 structure 1899:1907 cell wall structure 1889:1907 cell wall structure 1889:1907 Confocal scanning light microscopy (CSLM), transmission electron microscopy (TEM), and NMR characterization of solids from both pretreatments revealed differences in cell wall structure and lignin composition, location, coalescence, and migration-enhanced digestibility of CELF-pretreated solids. 29213312 1 6 theme Consolidated 199:210 arg1 bioprocessing 212:224 BACKGROUND Consolidated bioprocessing 188:224 BACKGROUND Consolidated bioprocessing (CBP) by anaerobes, such as Clostridium thermocellum, which combine enzyme production 188:310 BACKGROUND Consolidated bioprocessing (CBP) by anaerobes, such as Clostridium thermocellum, which combine enzyme production, hydrolysis, and fermentation are promising alternatives to historical economic challenges of using fungal enzymes for biological conversion of lignocellulosic biomass. 29213312 1 6 theme Consolidated 199:210 arg1 hydrolysis 313:322 hydrolysis 313:322 hydrolysis 313:322 BACKGROUND Consolidated bioprocessing (CBP) by anaerobes, such as Clostridium thermocellum, which combine enzyme production, hydrolysis, and fermentation are promising alternatives to historical economic challenges of using fungal enzymes for biological conversion of lignocellulosic biomass. 29213312 1 6 theme Consolidated 199:210 arg1 fermentation 329:340 fermentation 329:340 fermentation 329:340 BACKGROUND Consolidated bioprocessing (CBP) by anaerobes, such as Clostridium thermocellum, which combine enzyme production, hydrolysis, and fermentation are promising alternatives to historical economic challenges of using fungal enzymes for biological conversion of lignocellulosic biomass. 29213312 1 6 theme Consolidated 199:210 arg1 alternatives 356:367 promising alternatives 346:367 promising alternatives to historical economic challenges of using fungal enzymes for biological conversion of lignocellulosic biomass 346:478 BACKGROUND Consolidated bioprocessing (CBP) by anaerobes, such as Clostridium thermocellum, which combine enzyme production, hydrolysis, and fermentation are promising alternatives to historical economic challenges of using fungal enzymes for biological conversion of lignocellulosic biomass. 29213312 1 6 theme Consolidated 199:210 arg1 CBP 227:229 CBP 227:229 CBP 227:229 BACKGROUND Consolidated bioprocessing (CBP) by anaerobes, such as Clostridium thermocellum, which combine enzyme production, hydrolysis, and fermentation are promising alternatives to historical economic challenges of using fungal enzymes for biological conversion of lignocellulosic biomass. 29213312 7 7 from characterization 1814:1829 arg1 pretreatments 1851:1863 both pretreatments 1846:1863 both pretreatments 1846:1863 Confocal scanning light microscopy (CSLM), transmission electron microscopy (TEM), and NMR characterization of solids from both pretreatments revealed differences in cell wall structure and lignin composition, location, coalescence, and migration-enhanced digestibility of CELF-pretreated solids. 29213312 3 8 from effect 787:792 arg1 deconstruction 949:962 deconstruction 949:962 deconstruction of corn stover and Populus with much different recalcitrance by C. thermocellum vs. fungal enzymes and changes in pretreated biomass related to these differences 949:1124 This study focused on determining the effect of pretreatment by dilute sulfuric acid alone (DA) and with tetrahydrofuran (THF) addition via co-solvent-enhanced lignocellulosic fractionation (CELF) on deconstruction of corn stover and Populus with much different recalcitrance by C. thermocellum vs. fungal enzymes and changes in pretreated biomass related to these differences. 29213312 3 9 theme sulfuric 820:827 arg1 acid 829:832 dilute sulfuric acid 813:832 dilute sulfuric acid alone (DA) 813:843 This study focused on determining the effect of pretreatment by dilute sulfuric acid alone (DA) and with tetrahydrofuran (THF) addition via co-solvent-enhanced lignocellulosic fractionation (CELF) on deconstruction of corn stover and Populus with much different recalcitrance by C. thermocellum vs. fungal enzymes and changes in pretreated biomass related to these differences. 29213312 3 9 theme sulfuric 820:827 arg1 DA 841:842 DA 841:842 DA 841:842 This study focused on determining the effect of pretreatment by dilute sulfuric acid alone (DA) and with tetrahydrofuran (THF) addition via co-solvent-enhanced lignocellulosic fractionation (CELF) on deconstruction of corn stover and Populus with much different recalcitrance by C. thermocellum vs. fungal enzymes and changes in pretreated biomass related to these differences. 29213312 3 10 theme pretreated 1078:1087 arg1 biomass 1089:1095 pretreated biomass 1078:1095 pretreated biomass related to these differences 1078:1124 This study focused on determining the effect of pretreatment by dilute sulfuric acid alone (DA) and with tetrahydrofuran (THF) addition via co-solvent-enhanced lignocellulosic fractionation (CELF) on deconstruction of corn stover and Populus with much different recalcitrance by C. thermocellum vs. fungal enzymes and changes in pretreated biomass related to these differences. 29213312 1 11 theme fungal 412:417 arg1 enzymes 419:425 fungal enzymes 412:425 fungal enzymes for biological conversion of lignocellulosic biomass 412:478 BACKGROUND Consolidated bioprocessing (CBP) by anaerobes, such as Clostridium thermocellum, which combine enzyme production, hydrolysis, and fermentation are promising alternatives to historical economic challenges of using fungal enzymes for biological conversion of lignocellulosic biomass. 29213312 7 12 theme light 1741:1745 arg1 CSLM 1759:1762 CSLM 1759:1762 CSLM 1759:1762 Confocal scanning light microscopy (CSLM), transmission electron microscopy (TEM), and NMR characterization of solids from both pretreatments revealed differences in cell wall structure and lignin composition, location, coalescence, and migration-enhanced digestibility of CELF-pretreated solids. 29213312 7 12 theme light 1741:1745 arg1 microscopy 1747:1756 Confocal scanning light microscopy 1723:1756 Confocal scanning light microscopy (CSLM) 1723:1763 Confocal scanning light microscopy (CSLM), transmission electron microscopy (TEM), and NMR characterization of solids from both pretreatments revealed differences in cell wall structure and lignin composition, location, coalescence, and migration-enhanced digestibility of CELF-pretreated solids. 29213312 0 13 theme Clostridium 143:153 arg1 thermocellum 155:166 Clostridium thermocellum 143:166 Clostridium thermocellum 143:166 Adding tetrahydrofuran to dilute acid pretreatment provides new insights into substrate changes that greatly enhance biomass deconstruction by Clostridium thermocellum and fungal enzymes. 29213312 7 14 theme Confocal 1723:1730 arg1 CSLM 1759:1762 CSLM 1759:1762 CSLM 1759:1762 Confocal scanning light microscopy (CSLM), transmission electron microscopy (TEM), and NMR characterization of solids from both pretreatments revealed differences in cell wall structure and lignin composition, location, coalescence, and migration-enhanced digestibility of CELF-pretreated solids. 29213312 7 14 theme Confocal 1723:1730 arg1 microscopy 1747:1756 Confocal scanning light microscopy 1723:1756 Confocal scanning light microscopy (CSLM) 1723:1763 Confocal scanning light microscopy (CSLM), transmission electron microscopy (TEM), and NMR characterization of solids from both pretreatments revealed differences in cell wall structure and lignin composition, location, coalescence, and migration-enhanced digestibility of CELF-pretreated solids. 29213312 2 15 theme fungal 636:641 arg1 enzymes 643:649 fungal enzymes 636:649 fungal enzymes 636:649 However, limited research has integrated CBP with real pretreated biomass, and understanding how pretreatment impacts subsequent deconstruction by CBP vs. fungal enzymes can provide valuable insights into CBP and suggest other novel biomass deconstruction strategies. 29213312 10 16 theme biomass 2663:2669 arg1 recalcitrance 2671:2683 biomass recalcitrance 2663:2683 biomass recalcitrance 2663:2683 Overall, enhanced deconstruction of CELF solids by enzymes and particularly by C. thermocellum could be related to lignin removal and alteration, thereby pointing to these factors being key contributors to biomass recalcitrance as a barrier to low-cost biological conversion to sustainable fuels. 29213312 6 17 theme corn 1692:1695 arg1 stover 1697:1702 corn stover 1692:1702 corn stover 1692:1702 Enzyme adsorption on CELF-pretreated corn stover and CELF-pretreated Populus solids were virtually equal, while DA improved the enzyme accessibility for corn stover more than Populus. 29213312 7 18 theme solids 1834:1839 arg1 microscopy 1788:1797 transmission electron microscopy 1766:1797 transmission electron microscopy (TEM) 1766:1803 Confocal scanning light microscopy (CSLM), transmission electron microscopy (TEM), and NMR characterization of solids from both pretreatments revealed differences in cell wall structure and lignin composition, location, coalescence, and migration-enhanced digestibility of CELF-pretreated solids. 29213312 7 18 theme solids 1834:1839 arg1 CSLM 1759:1762 CSLM 1759:1762 CSLM 1759:1762 Confocal scanning light microscopy (CSLM), transmission electron microscopy (TEM), and NMR characterization of solids from both pretreatments revealed differences in cell wall structure and lignin composition, location, coalescence, and migration-enhanced digestibility of CELF-pretreated solids. 29213312 7 18 theme solids 1834:1839 arg1 microscopy 1747:1756 Confocal scanning light microscopy 1723:1756 Confocal scanning light microscopy (CSLM) 1723:1763 Confocal scanning light microscopy (CSLM), transmission electron microscopy (TEM), and NMR characterization of solids from both pretreatments revealed differences in cell wall structure and lignin composition, location, coalescence, and migration-enhanced digestibility of CELF-pretreated solids. 29213312 7 18 theme solids 1834:1839 arg1 characterization 1814:1829 NMR characterization 1810:1829 NMR characterization 1810:1829 Confocal scanning light microscopy (CSLM), transmission electron microscopy (TEM), and NMR characterization of solids from both pretreatments revealed differences in cell wall structure and lignin composition, location, coalescence, and migration-enhanced digestibility of CELF-pretreated solids. 29213312 7 18 theme solids 1834:1839 arg1 TEM 1800:1802 TEM 1800:1802 TEM 1800:1802 Confocal scanning light microscopy (CSLM), transmission electron microscopy (TEM), and NMR characterization of solids from both pretreatments revealed differences in cell wall structure and lignin composition, location, coalescence, and migration-enhanced digestibility of CELF-pretreated solids. 29213312 10 19 theme enhanced 2466:2473 arg1 deconstruction 2475:2488 enhanced deconstruction 2466:2488 enhanced deconstruction of CELF solids by enzymes and particularly by C. thermocellum 2466:2550 Overall, enhanced deconstruction of CELF solids by enzymes and particularly by C. thermocellum could be related to lignin removal and alteration, thereby pointing to these factors being key contributors to biomass recalcitrance as a barrier to low-cost biological conversion to sustainable fuels. 29213312 3 20 theme tetrahydrofuran 854:868 arg1 addition 876:883 tetrahydrofuran (THF) addition 854:883 tetrahydrofuran (THF) addition via co-solvent-enhanced lignocellulosic fractionation (CELF) 854:944 This study focused on determining the effect of pretreatment by dilute sulfuric acid alone (DA) and with tetrahydrofuran (THF) addition via co-solvent-enhanced lignocellulosic fractionation (CELF) on deconstruction of corn stover and Populus with much different recalcitrance by C. thermocellum vs. fungal enzymes and changes in pretreated biomass related to these differences. 29213312 1 21 theme lignocellulosic 456:470 arg1 biomass 472:478 lignocellulosic biomass 456:478 lignocellulosic biomass 456:478 BACKGROUND Consolidated bioprocessing (CBP) by anaerobes, such as Clostridium thermocellum, which combine enzyme production, hydrolysis, and fermentation are promising alternatives to historical economic challenges of using fungal enzymes for biological conversion of lignocellulosic biomass. 29213312 7 22 theme transmission 1766:1777 arg1 microscopy 1788:1797 transmission electron microscopy 1766:1797 transmission electron microscopy (TEM) 1766:1803 Confocal scanning light microscopy (CSLM), transmission electron microscopy (TEM), and NMR characterization of solids from both pretreatments revealed differences in cell wall structure and lignin composition, location, coalescence, and migration-enhanced digestibility of CELF-pretreated solids. 29213312 7 22 theme transmission 1766:1777 arg1 TEM 1800:1802 TEM 1800:1802 TEM 1800:1802 Confocal scanning light microscopy (CSLM), transmission electron microscopy (TEM), and NMR characterization of solids from both pretreatments revealed differences in cell wall structure and lignin composition, location, coalescence, and migration-enhanced digestibility of CELF-pretreated solids. 29213312 3 23 theme co-solvent-enhanced 889:907 arg1 fractionation 925:937 co-solvent-enhanced lignocellulosic fractionation 889:937 co-solvent-enhanced lignocellulosic fractionation (CELF) 889:944 This study focused on determining the effect of pretreatment by dilute sulfuric acid alone (DA) and with tetrahydrofuran (THF) addition via co-solvent-enhanced lignocellulosic fractionation (CELF) on deconstruction of corn stover and Populus with much different recalcitrance by C. thermocellum vs. fungal enzymes and changes in pretreated biomass related to these differences. 29213312 3 23 theme co-solvent-enhanced 889:907 arg1 CELF 940:943 CELF 940:943 CELF 940:943 This study focused on determining the effect of pretreatment by dilute sulfuric acid alone (DA) and with tetrahydrofuran (THF) addition via co-solvent-enhanced lignocellulosic fractionation (CELF) on deconstruction of corn stover and Populus with much different recalcitrance by C. thermocellum vs. fungal enzymes and changes in pretreated biomass related to these differences. 29213312 8 24 theme C. 2150:2151 arg1 CBP 2166:2168 C. thermocellum CBP 2150:2168 C. thermocellum CBP 2150:2168 CONCLUSIONS Adding THF to DA pretreatment (CELF) greatly enhanced deconstruction of corn stover and Populus by fungal enzymes and C. thermocellum CBP, and the CELF-CBP tandem was agnostic to feedstock recalcitrance. 29213312 1 25 theme promising 346:354 arg1 bioprocessing 212:224 BACKGROUND Consolidated bioprocessing 188:224 BACKGROUND Consolidated bioprocessing (CBP) by anaerobes, such as Clostridium thermocellum, which combine enzyme production 188:310 BACKGROUND Consolidated bioprocessing (CBP) by anaerobes, such as Clostridium thermocellum, which combine enzyme production, hydrolysis, and fermentation are promising alternatives to historical economic challenges of using fungal enzymes for biological conversion of lignocellulosic biomass. 29213312 1 25 theme promising 346:354 arg1 hydrolysis 313:322 hydrolysis 313:322 hydrolysis 313:322 BACKGROUND Consolidated bioprocessing (CBP) by anaerobes, such as Clostridium thermocellum, which combine enzyme production, hydrolysis, and fermentation are promising alternatives to historical economic challenges of using fungal enzymes for biological conversion of lignocellulosic biomass. 29213312 1 25 theme promising 346:354 arg1 fermentation 329:340 fermentation 329:340 fermentation 329:340 BACKGROUND Consolidated bioprocessing (CBP) by anaerobes, such as Clostridium thermocellum, which combine enzyme production, hydrolysis, and fermentation are promising alternatives to historical economic challenges of using fungal enzymes for biological conversion of lignocellulosic biomass. 29213312 1 25 theme promising 346:354 arg1 alternatives 356:367 promising alternatives 346:367 promising alternatives to historical economic challenges of using fungal enzymes for biological conversion of lignocellulosic biomass 346:478 BACKGROUND Consolidated bioprocessing (CBP) by anaerobes, such as Clostridium thermocellum, which combine enzyme production, hydrolysis, and fermentation are promising alternatives to historical economic challenges of using fungal enzymes for biological conversion of lignocellulosic biomass. 29213312 2 26 theme real 531:534 arg1 biomass 547:553 real pretreated biomass 531:553 real pretreated biomass 531:553 However, limited research has integrated CBP with real pretreated biomass, and understanding how pretreatment impacts subsequent deconstruction by CBP vs. fungal enzymes can provide valuable insights into CBP and suggest other novel biomass deconstruction strategies. 29213312 0 27 theme substrate 78:86 arg1 changes 88:94 substrate changes 78:94 substrate changes that greatly enhance biomass deconstruction by Clostridium thermocellum and fungal enzymes 78:185 Adding tetrahydrofuran to dilute acid pretreatment provides new insights into substrate changes that greatly enhance biomass deconstruction by Clostridium thermocellum and fungal enzymes. 29213312 2 28 theme novel 708:712 arg1 strategies 737:746 other novel biomass deconstruction strategies 702:746 other novel biomass deconstruction strategies 702:746 However, limited research has integrated CBP with real pretreated biomass, and understanding how pretreatment impacts subsequent deconstruction by CBP vs. fungal enzymes can provide valuable insights into CBP and suggest other novel biomass deconstruction strategies. 29213312 3 29 theme THF 871:873 arg1 addition 876:883 tetrahydrofuran (THF) addition 854:883 tetrahydrofuran (THF) addition via co-solvent-enhanced lignocellulosic fractionation (CELF) 854:944 This study focused on determining the effect of pretreatment by dilute sulfuric acid alone (DA) and with tetrahydrofuran (THF) addition via co-solvent-enhanced lignocellulosic fractionation (CELF) on deconstruction of corn stover and Populus with much different recalcitrance by C. thermocellum vs. fungal enzymes and changes in pretreated biomass related to these differences. 29213312 8 30 theme corn 2104:2107 arg1 stover 2109:2114 corn stover 2104:2114 corn stover 2104:2114 CONCLUSIONS Adding THF to DA pretreatment (CELF) greatly enhanced deconstruction of corn stover and Populus by fungal enzymes and C. thermocellum CBP, and the CELF-CBP tandem was agnostic to feedstock recalcitrance. 29213312 1 31 theme economic 383:390 arg1 challenges 392:401 historical economic challenges 372:401 historical economic challenges of using fungal enzymes for biological conversion of lignocellulosic biomass 372:478 BACKGROUND Consolidated bioprocessing (CBP) by anaerobes, such as Clostridium thermocellum, which combine enzyme production, hydrolysis, and fermentation are promising alternatives to historical economic challenges of using fungal enzymes for biological conversion of lignocellulosic biomass. 29213312 4 32 dep RESULTS 1127:1133 arg1 solubilized 1253:1263 solubilized 1253:1263 solubilized polysaccharides left in the pretreated solids within only 48 h without adding enzymes 1253:1349 RESULTS Coupling CELF fractionation of corn stover and Populus with subsequent CBP by the anaerobe C. thermocellum completely solubilized polysaccharides left in the pretreated solids within only 48 h without adding enzymes. 29213312 3 33 theme stover 972:977 arg1 deconstruction 949:962 deconstruction 949:962 deconstruction of corn stover and Populus with much different recalcitrance by C. thermocellum vs. fungal enzymes and changes in pretreated biomass related to these differences 949:1124 This study focused on determining the effect of pretreatment by dilute sulfuric acid alone (DA) and with tetrahydrofuran (THF) addition via co-solvent-enhanced lignocellulosic fractionation (CELF) on deconstruction of corn stover and Populus with much different recalcitrance by C. thermocellum vs. fungal enzymes and changes in pretreated biomass related to these differences. 29213312 4 34 theme adding 1336:1341 arg1 enzymes 1343:1349 adding enzymes 1336:1349 adding enzymes 1336:1349 RESULTS Coupling CELF fractionation of corn stover and Populus with subsequent CBP by the anaerobe C. thermocellum completely solubilized polysaccharides left in the pretreated solids within only 48 h without adding enzymes. 29213312 10 35 theme low-cost 2701:2708 arg1 conversion 2721:2730 low-cost biological conversion 2701:2730 low-cost biological conversion to sustainable fuels 2701:2751 Overall, enhanced deconstruction of CELF solids by enzymes and particularly by C. thermocellum could be related to lignin removal and alteration, thereby pointing to these factors being key contributors to biomass recalcitrance as a barrier to low-cost biological conversion to sustainable fuels. 29213312 9 36 theme cell 2383:2386 arg1 fractures 2393:2401 cell wall fractures 2383:2401 cell wall fractures 2383:2401 Composition measurements, material balances, cellulase adsorption, and CSLM and TEM imaging revealed adding THF enhanced the enzyme accessibility, cell wall fractures, and cellular dislocation and cell wall delamination. 29213312 7 37 theme electron 1779:1786 arg1 microscopy 1788:1797 transmission electron microscopy 1766:1797 transmission electron microscopy (TEM) 1766:1803 Confocal scanning light microscopy (CSLM), transmission electron microscopy (TEM), and NMR characterization of solids from both pretreatments revealed differences in cell wall structure and lignin composition, location, coalescence, and migration-enhanced digestibility of CELF-pretreated solids. 29213312 7 37 theme electron 1779:1786 arg1 TEM 1800:1802 TEM 1800:1802 TEM 1800:1802 Confocal scanning light microscopy (CSLM), transmission electron microscopy (TEM), and NMR characterization of solids from both pretreatments revealed differences in cell wall structure and lignin composition, location, coalescence, and migration-enhanced digestibility of CELF-pretreated solids. 29213312 2 38 theme limited 490:496 arg1 research 498:505 limited research 490:505 limited research 490:505 However, limited research has integrated CBP with real pretreated biomass, and understanding how pretreatment impacts subsequent deconstruction by CBP vs. fungal enzymes can provide valuable insights into CBP and suggest other novel biomass deconstruction strategies. 29213312 4 39 theme pretreated 1293:1302 arg1 solids 1304:1309 the pretreated solids 1289:1309 the pretreated solids within only 48 h without adding enzymes 1289:1349 RESULTS Coupling CELF fractionation of corn stover and Populus with subsequent CBP by the anaerobe C. thermocellum completely solubilized polysaccharides left in the pretreated solids within only 48 h without adding enzymes. 29213312 9 40 theme material 2262:2269 arg1 balances 2271:2278 material balances 2262:2278 material balances 2262:2278 Composition measurements, material balances, cellulase adsorption, and CSLM and TEM imaging revealed adding THF enhanced the enzyme accessibility, cell wall fractures, and cellular dislocation and cell wall delamination. 29213312 1 41 theme enzyme 294:299 arg1 production 301:310 enzyme production 294:310 enzyme production 294:310 BACKGROUND Consolidated bioprocessing (CBP) by anaerobes, such as Clostridium thermocellum, which combine enzyme production, hydrolysis, and fermentation are promising alternatives to historical economic challenges of using fungal enzymes for biological conversion of lignocellulosic biomass. 29213312 2 42 theme deconstruction 722:735 arg1 strategies 737:746 other novel biomass deconstruction strategies 702:746 other novel biomass deconstruction strategies 702:746 However, limited research has integrated CBP with real pretreated biomass, and understanding how pretreatment impacts subsequent deconstruction by CBP vs. fungal enzymes can provide valuable insights into CBP and suggest other novel biomass deconstruction strategies. 29213312 10 43 theme sustainable 2735:2745 arg1 fuels 2747:2751 sustainable fuels 2735:2751 sustainable fuels 2735:2751 Overall, enhanced deconstruction of CELF solids by enzymes and particularly by C. thermocellum could be related to lignin removal and alteration, thereby pointing to these factors being key contributors to biomass recalcitrance as a barrier to low-cost biological conversion to sustainable fuels. 29213312 5 44 theme conventional 1398:1409 arg1 DA 1411:1412 the conventional DA 1394:1412 the conventional DA followed by either CBP or fungal enzymes 1394:1453 These results were better than those from the conventional DA followed by either CBP or fungal enzymes or CELF followed by fungal enzyme hydrolysis, especially at viable enzyme loadings. 29213312 3 45 theme Populus 983:989 arg1 deconstruction 949:962 deconstruction 949:962 deconstruction of corn stover and Populus with much different recalcitrance by C. thermocellum vs. fungal enzymes and changes in pretreated biomass related to these differences 949:1124 This study focused on determining the effect of pretreatment by dilute sulfuric acid alone (DA) and with tetrahydrofuran (THF) addition via co-solvent-enhanced lignocellulosic fractionation (CELF) on deconstruction of corn stover and Populus with much different recalcitrance by C. thermocellum vs. fungal enzymes and changes in pretreated biomass related to these differences. 29213312 0 46 theme acid 33:36 arg1 pretreatment 38:49 dilute acid pretreatment 26:49 dilute acid pretreatment 26:49 Adding tetrahydrofuran to dilute acid pretreatment provides new insights into substrate changes that greatly enhance biomass deconstruction by Clostridium thermocellum and fungal enzymes. 29213312 2 47 dep understanding 560:572 arg1 impacts 591:597 impacts 591:597 impacts subsequent deconstruction by CBP vs. fungal enzymes 591:649 However, limited research has integrated CBP with real pretreated biomass, and understanding how pretreatment impacts subsequent deconstruction by CBP vs. fungal enzymes can provide valuable insights into CBP and suggest other novel biomass deconstruction strategies. 29213312 9 48 dep revealed 2328:2335 arg1 enhanced 2348:2355 enhanced 2348:2355 revealed adding THF enhanced the enzyme accessibility, cell wall fractures, and cellular dislocation and cell wall delamination 2328:2454 Composition measurements, material balances, cellulase adsorption, and CSLM and TEM imaging revealed adding THF enhanced the enzyme accessibility, cell wall fractures, and cellular dislocation and cell wall delamination. 29213312 10 49 theme lignin 2572:2577 arg1 removal 2579:2585 lignin removal 2572:2585 lignin removal 2572:2585 Overall, enhanced deconstruction of CELF solids by enzymes and particularly by C. thermocellum could be related to lignin removal and alteration, thereby pointing to these factors being key contributors to biomass recalcitrance as a barrier to low-cost biological conversion to sustainable fuels. 29213312 9 50 theme wall 2438:2441 arg1 delamination 2443:2454 and cell wall delamination 2429:2454 and cell wall delamination 2429:2454 Composition measurements, material balances, cellulase adsorption, and CSLM and TEM imaging revealed adding THF enhanced the enzyme accessibility, cell wall fractures, and cellular dislocation and cell wall delamination. 29213312 7 51 theme solids 2012:2017 arg1 composition 1920:1930 lignin composition 1913:1930 lignin composition 1913:1930 Confocal scanning light microscopy (CSLM), transmission electron microscopy (TEM), and NMR characterization of solids from both pretreatments revealed differences in cell wall structure and lignin composition, location, coalescence, and migration-enhanced digestibility of CELF-pretreated solids. 29213312 7 51 theme solids 2012:2017 arg1 digestibility 1979:1991 migration-enhanced digestibility 1960:1991 migration-enhanced digestibility 1960:1991 Confocal scanning light microscopy (CSLM), transmission electron microscopy (TEM), and NMR characterization of solids from both pretreatments revealed differences in cell wall structure and lignin composition, location, coalescence, and migration-enhanced digestibility of CELF-pretreated solids. 29213312 7 51 theme solids 2012:2017 arg1 coalescence 1943:1953 coalescence 1943:1953 coalescence 1943:1953 Confocal scanning light microscopy (CSLM), transmission electron microscopy (TEM), and NMR characterization of solids from both pretreatments revealed differences in cell wall structure and lignin composition, location, coalescence, and migration-enhanced digestibility of CELF-pretreated solids. 29213312 7 51 theme solids 2012:2017 arg1 location 1933:1940 location 1933:1940 location 1933:1940 Confocal scanning light microscopy (CSLM), transmission electron microscopy (TEM), and NMR characterization of solids from both pretreatments revealed differences in cell wall structure and lignin composition, location, coalescence, and migration-enhanced digestibility of CELF-pretreated solids. 29213312 7 51 theme solids 2012:2017 arg1 structure 1899:1907 cell wall structure 1889:1907 cell wall structure 1889:1907 Confocal scanning light microscopy (CSLM), transmission electron microscopy (TEM), and NMR characterization of solids from both pretreatments revealed differences in cell wall structure and lignin composition, location, coalescence, and migration-enhanced digestibility of CELF-pretreated solids. 29213312 9 52 dep accessibility 2368:2380 arg1 delamination 2443:2454 and cell wall delamination 2429:2454 and cell wall delamination 2429:2454 Composition measurements, material balances, cellulase adsorption, and CSLM and TEM imaging revealed adding THF enhanced the enzyme accessibility, cell wall fractures, and cellular dislocation and cell wall delamination. 29213312 7 53 from pretreatments 1851:1863 arg1 CSLM 1759:1762 CSLM 1759:1762 CSLM 1759:1762 Confocal scanning light microscopy (CSLM), transmission electron microscopy (TEM), and NMR characterization of solids from both pretreatments revealed differences in cell wall structure and lignin composition, location, coalescence, and migration-enhanced digestibility of CELF-pretreated solids. 29213312 7 53 from pretreatments 1851:1863 arg1 solids 1834:1839 solids 1834:1839 solids from both pretreatments 1834:1863 Confocal scanning light microscopy (CSLM), transmission electron microscopy (TEM), and NMR characterization of solids from both pretreatments revealed differences in cell wall structure and lignin composition, location, coalescence, and migration-enhanced digestibility of CELF-pretreated solids. 29213312 7 53 from pretreatments 1851:1863 arg1 microscopy 1747:1756 Confocal scanning light microscopy 1723:1756 Confocal scanning light microscopy (CSLM) 1723:1763 Confocal scanning light microscopy (CSLM), transmission electron microscopy (TEM), and NMR characterization of solids from both pretreatments revealed differences in cell wall structure and lignin composition, location, coalescence, and migration-enhanced digestibility of CELF-pretreated solids. 29213312 7 53 from pretreatments 1851:1863 arg1 microscopy 1788:1797 transmission electron microscopy 1766:1797 transmission electron microscopy (TEM) 1766:1803 Confocal scanning light microscopy (CSLM), transmission electron microscopy (TEM), and NMR characterization of solids from both pretreatments revealed differences in cell wall structure and lignin composition, location, coalescence, and migration-enhanced digestibility of CELF-pretreated solids. 29213312 7 53 from pretreatments 1851:1863 arg1 characterization 1814:1829 NMR characterization 1810:1829 NMR characterization 1810:1829 Confocal scanning light microscopy (CSLM), transmission electron microscopy (TEM), and NMR characterization of solids from both pretreatments revealed differences in cell wall structure and lignin composition, location, coalescence, and migration-enhanced digestibility of CELF-pretreated solids. 29213312 7 53 from pretreatments 1851:1863 arg1 TEM 1800:1802 TEM 1800:1802 TEM 1800:1802 Confocal scanning light microscopy (CSLM), transmission electron microscopy (TEM), and NMR characterization of solids from both pretreatments revealed differences in cell wall structure and lignin composition, location, coalescence, and migration-enhanced digestibility of CELF-pretreated solids. 29213312 5 54 theme enzyme 1482:1487 arg1 hydrolysis 1489:1498 fungal enzyme hydrolysis 1475:1498 fungal enzyme hydrolysis 1475:1498 These results were better than those from the conventional DA followed by either CBP or fungal enzymes or CELF followed by fungal enzyme hydrolysis, especially at viable enzyme loadings. 29213312 3 55 with effect 787:792 arg1 addition 876:883 tetrahydrofuran (THF) addition 854:883 tetrahydrofuran (THF) addition via co-solvent-enhanced lignocellulosic fractionation (CELF) 854:944 This study focused on determining the effect of pretreatment by dilute sulfuric acid alone (DA) and with tetrahydrofuran (THF) addition via co-solvent-enhanced lignocellulosic fractionation (CELF) on deconstruction of corn stover and Populus with much different recalcitrance by C. thermocellum vs. fungal enzymes and changes in pretreated biomass related to these differences. 29213312 7 56 theme migration-enhanced 1960:1977 arg1 digestibility 1979:1991 migration-enhanced digestibility 1960:1991 migration-enhanced digestibility 1960:1991 Confocal scanning light microscopy (CSLM), transmission electron microscopy (TEM), and NMR characterization of solids from both pretreatments revealed differences in cell wall structure and lignin composition, location, coalescence, and migration-enhanced digestibility of CELF-pretreated solids. 29213312 7 57 from differences 1874:1884 arg1 composition 1920:1930 lignin composition 1913:1930 lignin composition 1913:1930 Confocal scanning light microscopy (CSLM), transmission electron microscopy (TEM), and NMR characterization of solids from both pretreatments revealed differences in cell wall structure and lignin composition, location, coalescence, and migration-enhanced digestibility of CELF-pretreated solids. 29213312 7 57 from differences 1874:1884 arg1 structure 1899:1907 cell wall structure 1889:1907 cell wall structure 1889:1907 Confocal scanning light microscopy (CSLM), transmission electron microscopy (TEM), and NMR characterization of solids from both pretreatments revealed differences in cell wall structure and lignin composition, location, coalescence, and migration-enhanced digestibility of CELF-pretreated solids. 29213312 4 58 theme stover 1171:1176 arg1 fractionation 1149:1161 Coupling CELF fractionation 1135:1161 Coupling CELF fractionation of corn stover and Populus with subsequent CBP by the anaerobe C. thermocellum 1135:1240 RESULTS Coupling CELF fractionation of corn stover and Populus with subsequent CBP by the anaerobe C. thermocellum completely solubilized polysaccharides left in the pretreated solids within only 48 h without adding enzymes. 29213312 6 59 theme corn 1576:1579 arg1 stover 1581:1586 CELF-pretreated corn stover 1560:1586 CELF-pretreated corn stover 1560:1586 Enzyme adsorption on CELF-pretreated corn stover and CELF-pretreated Populus solids were virtually equal, while DA improved the enzyme accessibility for corn stover more than Populus. 29213312 10 60 theme solids 2498:2503 arg1 deconstruction 2475:2488 enhanced deconstruction 2466:2488 enhanced deconstruction of CELF solids by enzymes and particularly by C. thermocellum 2466:2550 Overall, enhanced deconstruction of CELF solids by enzymes and particularly by C. thermocellum could be related to lignin removal and alteration, thereby pointing to these factors being key contributors to biomass recalcitrance as a barrier to low-cost biological conversion to sustainable fuels. 29213312 7 61 theme wall 1894:1897 arg1 structure 1899:1907 cell wall structure 1889:1907 cell wall structure 1889:1907 Confocal scanning light microscopy (CSLM), transmission electron microscopy (TEM), and NMR characterization of solids from both pretreatments revealed differences in cell wall structure and lignin composition, location, coalescence, and migration-enhanced digestibility of CELF-pretreated solids. 29213312 4 62 theme CELF 1144:1147 arg1 fractionation 1149:1161 Coupling CELF fractionation 1135:1161 Coupling CELF fractionation of corn stover and Populus with subsequent CBP by the anaerobe C. thermocellum 1135:1240 RESULTS Coupling CELF fractionation of corn stover and Populus with subsequent CBP by the anaerobe C. thermocellum completely solubilized polysaccharides left in the pretreated solids within only 48 h without adding enzymes. 29213312 5 63 theme enzyme 1522:1527 arg1 loadings 1529:1536 viable enzyme loadings 1515:1536 viable enzyme loadings 1515:1536 These results were better than those from the conventional DA followed by either CBP or fungal enzymes or CELF followed by fungal enzyme hydrolysis, especially at viable enzyme loadings. 29213312 6 64 theme Enzyme 1539:1544 arg1 adsorption 1546:1555 Enzyme adsorption 1539:1555 Enzyme adsorption on CELF-pretreated corn stover and CELF-pretreated Populus solids 1539:1621 Enzyme adsorption on CELF-pretreated corn stover and CELF-pretreated Populus solids were virtually equal, while DA improved the enzyme accessibility for corn stover more than Populus. 29213312 3 65 theme pretreatment 797:808 arg1 effect 787:792 the effect 783:792 the effect of pretreatment by dilute sulfuric acid alone (DA) and with tetrahydrofuran (THF) addition via co-solvent-enhanced lignocellulosic fractionation (CELF) on deconstruction of corn stover and Populus with much different recalcitrance by C. thermocellum vs. fungal enzymes and changes in pretreated biomass related to these differences 783:1124 This study focused on determining the effect of pretreatment by dilute sulfuric acid alone (DA) and with tetrahydrofuran (THF) addition via co-solvent-enhanced lignocellulosic fractionation (CELF) on deconstruction of corn stover and Populus with much different recalcitrance by C. thermocellum vs. fungal enzymes and changes in pretreated biomass related to these differences. 29213312 1 66 theme BACKGROUND 188:197 arg1 bioprocessing 212:224 BACKGROUND Consolidated bioprocessing 188:224 BACKGROUND Consolidated bioprocessing (CBP) by anaerobes, such as Clostridium thermocellum, which combine enzyme production 188:310 BACKGROUND Consolidated bioprocessing (CBP) by anaerobes, such as Clostridium thermocellum, which combine enzyme production, hydrolysis, and fermentation are promising alternatives to historical economic challenges of using fungal enzymes for biological conversion of lignocellulosic biomass. 29213312 1 66 theme BACKGROUND 188:197 arg1 hydrolysis 313:322 hydrolysis 313:322 hydrolysis 313:322 BACKGROUND Consolidated bioprocessing (CBP) by anaerobes, such as Clostridium thermocellum, which combine enzyme production, hydrolysis, and fermentation are promising alternatives to historical economic challenges of using fungal enzymes for biological conversion of lignocellulosic biomass. 29213312 1 66 theme BACKGROUND 188:197 arg1 fermentation 329:340 fermentation 329:340 fermentation 329:340 BACKGROUND Consolidated bioprocessing (CBP) by anaerobes, such as Clostridium thermocellum, which combine enzyme production, hydrolysis, and fermentation are promising alternatives to historical economic challenges of using fungal enzymes for biological conversion of lignocellulosic biomass. 29213312 1 66 theme BACKGROUND 188:197 arg1 alternatives 356:367 promising alternatives 346:367 promising alternatives to historical economic challenges of using fungal enzymes for biological conversion of lignocellulosic biomass 346:478 BACKGROUND Consolidated bioprocessing (CBP) by anaerobes, such as Clostridium thermocellum, which combine enzyme production, hydrolysis, and fermentation are promising alternatives to historical economic challenges of using fungal enzymes for biological conversion of lignocellulosic biomass. 29213312 1 66 theme BACKGROUND 188:197 arg1 CBP 227:229 CBP 227:229 CBP 227:229 BACKGROUND Consolidated bioprocessing (CBP) by anaerobes, such as Clostridium thermocellum, which combine enzyme production, hydrolysis, and fermentation are promising alternatives to historical economic challenges of using fungal enzymes for biological conversion of lignocellulosic biomass. 29213312 9 67 dep CSLM 2307:2310 arg1 imaging 2320:2326 imaging 2320:2326 imaging 2320:2326 Composition measurements, material balances, cellulase adsorption, and CSLM and TEM imaging revealed adding THF enhanced the enzyme accessibility, cell wall fractures, and cellular dislocation and cell wall delamination. 29213312 9 68 theme cellulase 2281:2289 arg1 adsorption 2291:2300 cellulase adsorption 2281:2300 cellulase adsorption 2281:2300 Composition measurements, material balances, cellulase adsorption, and CSLM and TEM imaging revealed adding THF enhanced the enzyme accessibility, cell wall fractures, and cellular dislocation and cell wall delamination. 29213312 3 69 theme related 1097:1103 arg1 biomass 1089:1095 pretreated biomass 1078:1095 pretreated biomass related to these differences 1078:1124 This study focused on determining the effect of pretreatment by dilute sulfuric acid alone (DA) and with tetrahydrofuran (THF) addition via co-solvent-enhanced lignocellulosic fractionation (CELF) on deconstruction of corn stover and Populus with much different recalcitrance by C. thermocellum vs. fungal enzymes and changes in pretreated biomass related to these differences. 29213312 4 70 theme Populus 1182:1188 arg1 fractionation 1149:1161 Coupling CELF fractionation 1135:1161 Coupling CELF fractionation of corn stover and Populus with subsequent CBP by the anaerobe C. thermocellum 1135:1240 RESULTS Coupling CELF fractionation of corn stover and Populus with subsequent CBP by the anaerobe C. thermocellum completely solubilized polysaccharides left in the pretreated solids within only 48 h without adding enzymes. 29213312 7 71 theme scanning 1732:1739 arg1 CSLM 1759:1762 CSLM 1759:1762 CSLM 1759:1762 Confocal scanning light microscopy (CSLM), transmission electron microscopy (TEM), and NMR characterization of solids from both pretreatments revealed differences in cell wall structure and lignin composition, location, coalescence, and migration-enhanced digestibility of CELF-pretreated solids. 29213312 7 71 theme scanning 1732:1739 arg1 microscopy 1747:1756 Confocal scanning light microscopy 1723:1756 Confocal scanning light microscopy (CSLM) 1723:1763 Confocal scanning light microscopy (CSLM), transmission electron microscopy (TEM), and NMR characterization of solids from both pretreatments revealed differences in cell wall structure and lignin composition, location, coalescence, and migration-enhanced digestibility of CELF-pretreated solids. 29213312 2 72 theme subsequent 599:608 arg1 deconstruction 610:623 subsequent deconstruction 599:623 subsequent deconstruction by CBP vs. fungal enzymes 599:649 However, limited research has integrated CBP with real pretreated biomass, and understanding how pretreatment impacts subsequent deconstruction by CBP vs. fungal enzymes can provide valuable insights into CBP and suggest other novel biomass deconstruction strategies. 29213312 4 73 theme subsequent 1195:1204 arg1 CBP 1206:1208 subsequent CBP 1195:1208 subsequent CBP 1195:1208 RESULTS Coupling CELF fractionation of corn stover and Populus with subsequent CBP by the anaerobe C. thermocellum completely solubilized polysaccharides left in the pretreated solids within only 48 h without adding enzymes. 29213312 3 74 theme dilute 813:818 arg1 acid 829:832 dilute sulfuric acid 813:832 dilute sulfuric acid alone (DA) 813:843 This study focused on determining the effect of pretreatment by dilute sulfuric acid alone (DA) and with tetrahydrofuran (THF) addition via co-solvent-enhanced lignocellulosic fractionation (CELF) on deconstruction of corn stover and Populus with much different recalcitrance by C. thermocellum vs. fungal enzymes and changes in pretreated biomass related to these differences. 29213312 3 74 theme dilute 813:818 arg1 DA 841:842 DA 841:842 DA 841:842 This study focused on determining the effect of pretreatment by dilute sulfuric acid alone (DA) and with tetrahydrofuran (THF) addition via co-solvent-enhanced lignocellulosic fractionation (CELF) on deconstruction of corn stover and Populus with much different recalcitrance by C. thermocellum vs. fungal enzymes and changes in pretreated biomass related to these differences. 29213312 8 75 theme DA 2046:2047 arg1 CELF 2063:2066 CELF 2063:2066 CELF 2063:2066 CONCLUSIONS Adding THF to DA pretreatment (CELF) greatly enhanced deconstruction of corn stover and Populus by fungal enzymes and C. thermocellum CBP, and the CELF-CBP tandem was agnostic to feedstock recalcitrance. 29213312 8 75 theme DA 2046:2047 arg1 pretreatment 2049:2060 DA pretreatment 2046:2060 DA pretreatment (CELF) 2046:2067 CONCLUSIONS Adding THF to DA pretreatment (CELF) greatly enhanced deconstruction of corn stover and Populus by fungal enzymes and C. thermocellum CBP, and the CELF-CBP tandem was agnostic to feedstock recalcitrance. 29213312 6 76 theme Populus 1608:1614 arg1 solids 1616:1621 CELF-pretreated Populus solids 1592:1621 CELF-pretreated Populus solids 1592:1621 Enzyme adsorption on CELF-pretreated corn stover and CELF-pretreated Populus solids were virtually equal, while DA improved the enzyme accessibility for corn stover more than Populus. 29213312 8 77 dep C. 2150:2151 arg1 thermocellum 2153:2164 thermocellum 2153:2164 thermocellum 2153:2164 CONCLUSIONS Adding THF to DA pretreatment (CELF) greatly enhanced deconstruction of corn stover and Populus by fungal enzymes and C. thermocellum CBP, and the CELF-CBP tandem was agnostic to feedstock recalcitrance. 29213312 0 78 theme fungal 172:177 arg1 enzymes 179:185 fungal enzymes 172:185 fungal enzymes 172:185 Adding tetrahydrofuran to dilute acid pretreatment provides new insights into substrate changes that greatly enhance biomass deconstruction by Clostridium thermocellum and fungal enzymes. 29213312 1 79 theme biological 431:440 arg1 conversion 442:451 biological conversion 431:451 biological conversion of lignocellulosic biomass 431:478 BACKGROUND Consolidated bioprocessing (CBP) by anaerobes, such as Clostridium thermocellum, which combine enzyme production, hydrolysis, and fermentation are promising alternatives to historical economic challenges of using fungal enzymes for biological conversion of lignocellulosic biomass. 29213312 1 80 theme historical 372:381 arg1 challenges 392:401 historical economic challenges 372:401 historical economic challenges of using fungal enzymes for biological conversion of lignocellulosic biomass 372:478 BACKGROUND Consolidated bioprocessing (CBP) by anaerobes, such as Clostridium thermocellum, which combine enzyme production, hydrolysis, and fermentation are promising alternatives to historical economic challenges of using fungal enzymes for biological conversion of lignocellulosic biomass. 29213312 7 81 from microscopy 1788:1797 arg1 pretreatments 1851:1863 both pretreatments 1846:1863 both pretreatments 1846:1863 Confocal scanning light microscopy (CSLM), transmission electron microscopy (TEM), and NMR characterization of solids from both pretreatments revealed differences in cell wall structure and lignin composition, location, coalescence, and migration-enhanced digestibility of CELF-pretreated solids. 29213312 10 82 theme key 2643:2645 arg1 contributors 2647:2658 key contributors 2643:2658 key contributors to biomass recalcitrance 2643:2683 Overall, enhanced deconstruction of CELF solids by enzymes and particularly by C. thermocellum could be related to lignin removal and alteration, thereby pointing to these factors being key contributors to biomass recalcitrance as a barrier to low-cost biological conversion to sustainable fuels. 29213312 9 83 theme adding 2337:2342 arg1 THF 2344:2346 adding THF 2337:2346 adding THF 2337:2346 Composition measurements, material balances, cellulase adsorption, and CSLM and TEM imaging revealed adding THF enhanced the enzyme accessibility, cell wall fractures, and cellular dislocation and cell wall delamination. 29213312 1 84 theme biomass 472:478 arg1 conversion 442:451 biological conversion 431:451 biological conversion of lignocellulosic biomass 431:478 BACKGROUND Consolidated bioprocessing (CBP) by anaerobes, such as Clostridium thermocellum, which combine enzyme production, hydrolysis, and fermentation are promising alternatives to historical economic challenges of using fungal enzymes for biological conversion of lignocellulosic biomass. 29213312 6 85 theme enzyme 1667:1672 arg1 accessibility 1674:1686 the enzyme accessibility 1663:1686 the enzyme accessibility for corn stover 1663:1702 Enzyme adsorption on CELF-pretreated corn stover and CELF-pretreated Populus solids were virtually equal, while DA improved the enzyme accessibility for corn stover more than Populus. 29213312 3 86 theme lignocellulosic 909:923 arg1 fractionation 925:937 co-solvent-enhanced lignocellulosic fractionation 889:937 co-solvent-enhanced lignocellulosic fractionation (CELF) 889:944 This study focused on determining the effect of pretreatment by dilute sulfuric acid alone (DA) and with tetrahydrofuran (THF) addition via co-solvent-enhanced lignocellulosic fractionation (CELF) on deconstruction of corn stover and Populus with much different recalcitrance by C. thermocellum vs. fungal enzymes and changes in pretreated biomass related to these differences. 29213312 3 86 theme lignocellulosic 909:923 arg1 CELF 940:943 CELF 940:943 CELF 940:943 This study focused on determining the effect of pretreatment by dilute sulfuric acid alone (DA) and with tetrahydrofuran (THF) addition via co-solvent-enhanced lignocellulosic fractionation (CELF) on deconstruction of corn stover and Populus with much different recalcitrance by C. thermocellum vs. fungal enzymes and changes in pretreated biomass related to these differences. 29213312 2 87 theme pretreated 536:545 arg1 biomass 547:553 real pretreated biomass 531:553 real pretreated biomass 531:553 However, limited research has integrated CBP with real pretreated biomass, and understanding how pretreatment impacts subsequent deconstruction by CBP vs. fungal enzymes can provide valuable insights into CBP and suggest other novel biomass deconstruction strategies. 29213312 9 88 theme wall 2388:2391 arg1 fractures 2393:2401 cell wall fractures 2383:2401 cell wall fractures 2383:2401 Composition measurements, material balances, cellulase adsorption, and CSLM and TEM imaging revealed adding THF enhanced the enzyme accessibility, cell wall fractures, and cellular dislocation and cell wall delamination. 29213312 4 89 with stover 1171:1176 arg1 CBP 1206:1208 subsequent CBP 1195:1208 subsequent CBP 1195:1208 RESULTS Coupling CELF fractionation of corn stover and Populus with subsequent CBP by the anaerobe C. thermocellum completely solubilized polysaccharides left in the pretreated solids within only 48 h without adding enzymes. 29213312 7 90 theme NMR 1810:1812 arg1 characterization 1814:1829 NMR characterization 1810:1829 NMR characterization 1810:1829 Confocal scanning light microscopy (CSLM), transmission electron microscopy (TEM), and NMR characterization of solids from both pretreatments revealed differences in cell wall structure and lignin composition, location, coalescence, and migration-enhanced digestibility of CELF-pretreated solids. 29213312 10 91 theme CELF 2493:2496 arg1 solids 2498:2503 CELF solids 2493:2503 CELF solids 2493:2503 Overall, enhanced deconstruction of CELF solids by enzymes and particularly by C. thermocellum could be related to lignin removal and alteration, thereby pointing to these factors being key contributors to biomass recalcitrance as a barrier to low-cost biological conversion to sustainable fuels. 29213312 2 92 theme biomass 714:720 arg1 strategies 737:746 other novel biomass deconstruction strategies 702:746 other novel biomass deconstruction strategies 702:746 However, limited research has integrated CBP with real pretreated biomass, and understanding how pretreatment impacts subsequent deconstruction by CBP vs. fungal enzymes can provide valuable insights into CBP and suggest other novel biomass deconstruction strategies. 29213312 9 93 theme enzyme 2361:2366 arg1 accessibility 2368:2380 the enzyme accessibility 2357:2380 the enzyme accessibility 2357:2380 Composition measurements, material balances, cellulase adsorption, and CSLM and TEM imaging revealed adding THF enhanced the enzyme accessibility, cell wall fractures, and cellular dislocation and cell wall delamination. 29213312 8 94 theme stover 2109:2114 arg1 deconstruction 2086:2099 deconstruction 2086:2099 deconstruction of corn stover and Populus by fungal enzymes and C. thermocellum CBP 2086:2168 CONCLUSIONS Adding THF to DA pretreatment (CELF) greatly enhanced deconstruction of corn stover and Populus by fungal enzymes and C. thermocellum CBP, and the CELF-CBP tandem was agnostic to feedstock recalcitrance. 29213312 3 95 with deconstruction 949:962 arg1 changes 1067:1073 changes 1067:1073 changes in pretreated biomass related to these differences 1067:1124 This study focused on determining the effect of pretreatment by dilute sulfuric acid alone (DA) and with tetrahydrofuran (THF) addition via co-solvent-enhanced lignocellulosic fractionation (CELF) on deconstruction of corn stover and Populus with much different recalcitrance by C. thermocellum vs. fungal enzymes and changes in pretreated biomass related to these differences. 29213312 3 95 with deconstruction 949:962 arg1 recalcitrance 1011:1023 much different recalcitrance 996:1023 much different recalcitrance by C. thermocellum vs. fungal enzymes 996:1061 This study focused on determining the effect of pretreatment by dilute sulfuric acid alone (DA) and with tetrahydrofuran (THF) addition via co-solvent-enhanced lignocellulosic fractionation (CELF) on deconstruction of corn stover and Populus with much different recalcitrance by C. thermocellum vs. fungal enzymes and changes in pretreated biomass related to these differences. 29213312 2 96 theme other 702:706 arg1 strategies 737:746 other novel biomass deconstruction strategies 702:746 other novel biomass deconstruction strategies 702:746 However, limited research has integrated CBP with real pretreated biomass, and understanding how pretreatment impacts subsequent deconstruction by CBP vs. fungal enzymes can provide valuable insights into CBP and suggest other novel biomass deconstruction strategies. 29213312 10 97 theme biological 2710:2719 arg1 conversion 2721:2730 low-cost biological conversion 2701:2730 low-cost biological conversion to sustainable fuels 2701:2751 Overall, enhanced deconstruction of CELF solids by enzymes and particularly by C. thermocellum could be related to lignin removal and alteration, thereby pointing to these factors being key contributors to biomass recalcitrance as a barrier to low-cost biological conversion to sustainable fuels. 29213312 0 98 theme biomass 117:123 arg1 deconstruction 125:138 biomass deconstruction 117:138 biomass deconstruction 117:138 Adding tetrahydrofuran to dilute acid pretreatment provides new insights into substrate changes that greatly enhance biomass deconstruction by Clostridium thermocellum and fungal enzymes. 29213312 8 99 theme Populus 2120:2126 arg1 deconstruction 2086:2099 deconstruction 2086:2099 deconstruction of corn stover and Populus by fungal enzymes and C. thermocellum CBP 2086:2168 CONCLUSIONS Adding THF to DA pretreatment (CELF) greatly enhanced deconstruction of corn stover and Populus by fungal enzymes and C. thermocellum CBP, and the CELF-CBP tandem was agnostic to feedstock recalcitrance. 29213312 8 100 theme fungal 2131:2136 arg1 enzymes 2138:2144 fungal enzymes 2131:2144 fungal enzymes 2131:2144 CONCLUSIONS Adding THF to DA pretreatment (CELF) greatly enhanced deconstruction of corn stover and Populus by fungal enzymes and C. thermocellum CBP, and the CELF-CBP tandem was agnostic to feedstock recalcitrance. 29213312 7 101 from microscopy 1747:1756 arg1 pretreatments 1851:1863 both pretreatments 1846:1863 both pretreatments 1846:1863 Confocal scanning light microscopy (CSLM), transmission electron microscopy (TEM), and NMR characterization of solids from both pretreatments revealed differences in cell wall structure and lignin composition, location, coalescence, and migration-enhanced digestibility of CELF-pretreated solids. 29213312 3 102 theme corn 967:970 arg1 stover 972:977 corn stover 967:977 corn stover 967:977 This study focused on determining the effect of pretreatment by dilute sulfuric acid alone (DA) and with tetrahydrofuran (THF) addition via co-solvent-enhanced lignocellulosic fractionation (CELF) on deconstruction of corn stover and Populus with much different recalcitrance by C. thermocellum vs. fungal enzymes and changes in pretreated biomass related to these differences. 29213312 4 103 theme only 1318:1321 arg1 48 h 1323:1326 only 48 h 1318:1326 only 48 h without adding enzymes 1318:1349 RESULTS Coupling CELF fractionation of corn stover and Populus with subsequent CBP by the anaerobe C. thermocellum completely solubilized polysaccharides left in the pretreated solids within only 48 h without adding enzymes. 29213312 0 104 theme dilute 26:31 arg1 pretreatment 38:49 dilute acid pretreatment 26:49 dilute acid pretreatment 26:49 Adding tetrahydrofuran to dilute acid pretreatment provides new insights into substrate changes that greatly enhance biomass deconstruction by Clostridium thermocellum and fungal enzymes. 29213312 4 105 from solids 1304:1309 arg1 left 1281:1284 left 1281:1284 left 1281:1284 RESULTS Coupling CELF fractionation of corn stover and Populus with subsequent CBP by the anaerobe C. thermocellum completely solubilized polysaccharides left in the pretreated solids within only 48 h without adding enzymes. 29213312 3 106 theme different 1001:1009 arg1 recalcitrance 1011:1023 much different recalcitrance 996:1023 much different recalcitrance by C. thermocellum vs. fungal enzymes 996:1061 This study focused on determining the effect of pretreatment by dilute sulfuric acid alone (DA) and with tetrahydrofuran (THF) addition via co-solvent-enhanced lignocellulosic fractionation (CELF) on deconstruction of corn stover and Populus with much different recalcitrance by C. thermocellum vs. fungal enzymes and changes in pretreated biomass related to these differences. 29213312 3 107 from recalcitrance 1011:1023 arg1 biomass 1089:1095 pretreated biomass 1078:1095 pretreated biomass related to these differences 1078:1124 This study focused on determining the effect of pretreatment by dilute sulfuric acid alone (DA) and with tetrahydrofuran (THF) addition via co-solvent-enhanced lignocellulosic fractionation (CELF) on deconstruction of corn stover and Populus with much different recalcitrance by C. thermocellum vs. fungal enzymes and changes in pretreated biomass related to these differences. 29213312 7 108 theme lignin 1913:1918 arg1 composition 1920:1930 lignin composition 1913:1930 lignin composition 1913:1930 Confocal scanning light microscopy (CSLM), transmission electron microscopy (TEM), and NMR characterization of solids from both pretreatments revealed differences in cell wall structure and lignin composition, location, coalescence, and migration-enhanced digestibility of CELF-pretreated solids. 29213312 9 109 theme cellular 2408:2415 arg1 dislocation 2417:2427 cellular dislocation 2408:2427 cellular dislocation 2408:2427 Composition measurements, material balances, cellulase adsorption, and CSLM and TEM imaging revealed adding THF enhanced the enzyme accessibility, cell wall fractures, and cellular dislocation and cell wall delamination. 29213312 7 110 theme CELF-pretreated 1996:2010 arg1 solids 2012:2017 CELF-pretreated solids 1996:2017 CELF-pretreated solids 1996:2017 Confocal scanning light microscopy (CSLM), transmission electron microscopy (TEM), and NMR characterization of solids from both pretreatments revealed differences in cell wall structure and lignin composition, location, coalescence, and migration-enhanced digestibility of CELF-pretreated solids. 29213312 5 111 dep enzymes 1447:1453 arg1 either 1426:1431 either 1426:1431 either 1426:1431 These results were better than those from the conventional DA followed by either CBP or fungal enzymes or CELF followed by fungal enzyme hydrolysis, especially at viable enzyme loadings. 29213312 5 111 dep enzymes 1447:1453 arg1 fungal 1440:1445 fungal 1440:1445 fungal 1440:1445 These results were better than those from the conventional DA followed by either CBP or fungal enzymes or CELF followed by fungal enzyme hydrolysis, especially at viable enzyme loadings. 29213312 8 112 theme feedstock 2211:2219 arg1 recalcitrance 2221:2233 feedstock recalcitrance 2211:2233 feedstock recalcitrance 2211:2233 CONCLUSIONS Adding THF to DA pretreatment (CELF) greatly enhanced deconstruction of corn stover and Populus by fungal enzymes and C. thermocellum CBP, and the CELF-CBP tandem was agnostic to feedstock recalcitrance. 29213312 9 113 theme and cell 2429:2436 arg1 delamination 2443:2454 and cell wall delamination 2429:2454 and cell wall delamination 2429:2454 Composition measurements, material balances, cellulase adsorption, and CSLM and TEM imaging revealed adding THF enhanced the enzyme accessibility, cell wall fractures, and cellular dislocation and cell wall delamination. 29213312 0 114 theme new 60:62 arg1 insights 64:71 new insights 60:71 new insights into substrate changes that greatly enhance biomass deconstruction by Clostridium thermocellum and fungal enzymes 60:185 Adding tetrahydrofuran to dilute acid pretreatment provides new insights into substrate changes that greatly enhance biomass deconstruction by Clostridium thermocellum and fungal enzymes. 29213312 4 115 from left 1281:1284 arg1 solids 1304:1309 the pretreated solids 1289:1309 the pretreated solids within only 48 h without adding enzymes 1289:1349 RESULTS Coupling CELF fractionation of corn stover and Populus with subsequent CBP by the anaerobe C. thermocellum completely solubilized polysaccharides left in the pretreated solids within only 48 h without adding enzymes. 29213312 5 116 theme fungal 1475:1480 arg1 hydrolysis 1489:1498 fungal enzyme hydrolysis 1475:1498 fungal enzyme hydrolysis 1475:1498 These results were better than those from the conventional DA followed by either CBP or fungal enzymes or CELF followed by fungal enzyme hydrolysis, especially at viable enzyme loadings. 29213312 6 117 theme CELF-pretreated 1592:1606 arg1 solids 1616:1621 CELF-pretreated Populus solids 1592:1621 CELF-pretreated Populus solids 1592:1621 Enzyme adsorption on CELF-pretreated corn stover and CELF-pretreated Populus solids were virtually equal, while DA improved the enzyme accessibility for corn stover more than Populus. 29213312 4 118 with Populus 1182:1188 arg1 CBP 1206:1208 subsequent CBP 1195:1208 subsequent CBP 1195:1208 RESULTS Coupling CELF fractionation of corn stover and Populus with subsequent CBP by the anaerobe C. thermocellum completely solubilized polysaccharides left in the pretreated solids within only 48 h without adding enzymes. 29213312 6 119 from adsorption 1546:1555 arg1 stover 1581:1586 CELF-pretreated corn stover 1560:1586 CELF-pretreated corn stover 1560:1586 Enzyme adsorption on CELF-pretreated corn stover and CELF-pretreated Populus solids were virtually equal, while DA improved the enzyme accessibility for corn stover more than Populus. 29213312 6 119 from adsorption 1546:1555 arg1 solids 1616:1621 CELF-pretreated Populus solids 1592:1621 CELF-pretreated Populus solids 1592:1621 Enzyme adsorption on CELF-pretreated corn stover and CELF-pretreated Populus solids were virtually equal, while DA improved the enzyme accessibility for corn stover more than Populus. 29213312 5 120 dep either 1426:1431 arg1 CBP 1433:1435 CBP 1433:1435 CBP 1433:1435 These results were better than those from the conventional DA followed by either CBP or fungal enzymes or CELF followed by fungal enzyme hydrolysis, especially at viable enzyme loadings. 29213312 3 121 from changes 1067:1073 arg1 biomass 1089:1095 pretreated biomass 1078:1095 pretreated biomass related to these differences 1078:1124 This study focused on determining the effect of pretreatment by dilute sulfuric acid alone (DA) and with tetrahydrofuran (THF) addition via co-solvent-enhanced lignocellulosic fractionation (CELF) on deconstruction of corn stover and Populus with much different recalcitrance by C. thermocellum vs. fungal enzymes and changes in pretreated biomass related to these differences. 29213312 4 122 theme corn 1166:1169 arg1 stover 1171:1176 corn stover 1166:1176 corn stover 1166:1176 RESULTS Coupling CELF fractionation of corn stover and Populus with subsequent CBP by the anaerobe C. thermocellum completely solubilized polysaccharides left in the pretreated solids within only 48 h without adding enzymes. 29213312 6 123 theme CELF-pretreated 1560:1574 arg1 stover 1581:1586 CELF-pretreated corn stover 1560:1586 CELF-pretreated corn stover 1560:1586 Enzyme adsorption on CELF-pretreated corn stover and CELF-pretreated Populus solids were virtually equal, while DA improved the enzyme accessibility for corn stover more than Populus. 29213312 1 124 theme Clostridium 254:264 arg1 thermocellum 266:277 Clostridium thermocellum 254:277 Clostridium thermocellum 254:277 BACKGROUND Consolidated bioprocessing (CBP) by anaerobes, such as Clostridium thermocellum, which combine enzyme production, hydrolysis, and fermentation are promising alternatives to historical economic challenges of using fungal enzymes for biological conversion of lignocellulosic biomass. 27775674 0 0 theme Skin 73:76 arg1 Tannins 78:84 Grape Skin Tannins 67:84 Grape Skin Tannins 67:84 A Fast and Robust UHPLC-MRM-MS Method to Characterize and Quantify Grape Skin Tannins after Chemical Depolymerization. 27775674 1 1 theme grape 350:354 arg1 flavan-3-ols 361:372 grape skin flavan-3-ols 350:372 grape skin flavan-3-ols after acid-catalysed depolymerization in the presence of phloroglucinol (phloroglucinolysis) 350:465 A rapid, sensitive, and selective analysis method using ultra high performance liquid chromatography coupled with triple-quadrupole mass spectrometry (UHPLC-QqQ-MS) has been developed for the characterization and quantification of grape skin flavan-3-ols after acid-catalysed depolymerization in the presence of phloroglucinol (phloroglucinolysis). 27775674 2 2 theme units 639:643 arg1 analysis 614:621 analysis 614:621 analysis of constitutive units of grape skin proanthocyanidins 614:675 The compound detection being based on specific MS transitions in Multiple Reaction Monitoring (MRM) mode, this fast gradient robust method allows analysis of constitutive units of grape skin proanthocyanidins, including some present in trace amounts, in a single injection, with a throughput of 6 samples per hour. 27775674 3 3 theme white 869:873 arg1 cultivars 881:889 107 different red and white grape cultivars 847:889 107 different red and white grape cultivars grown under two conditions in the vineyard, irrigated or non-irrigated 847:960 This method was applied to a set of 214 grape skin samples from 107 different red and white grape cultivars grown under two conditions in the vineyard, irrigated or non-irrigated. 27775674 0 4 theme Grape 67:71 arg1 Tannins 78:84 Grape Skin Tannins 67:84 Grape Skin Tannins 67:84 A Fast and Robust UHPLC-MRM-MS Method to Characterize and Quantify Grape Skin Tannins after Chemical Depolymerization. 27775674 1 5 theme skin 356:359 arg1 flavan-3-ols 361:372 grape skin flavan-3-ols 350:372 grape skin flavan-3-ols after acid-catalysed depolymerization in the presence of phloroglucinol (phloroglucinolysis) 350:465 A rapid, sensitive, and selective analysis method using ultra high performance liquid chromatography coupled with triple-quadrupole mass spectrometry (UHPLC-QqQ-MS) has been developed for the characterization and quantification of grape skin flavan-3-ols after acid-catalysed depolymerization in the presence of phloroglucinol (phloroglucinolysis). 27775674 2 6 theme constitutive 626:637 arg1 units 639:643 constitutive units 626:643 constitutive units of grape skin proanthocyanidins 626:675 The compound detection being based on specific MS transitions in Multiple Reaction Monitoring (MRM) mode, this fast gradient robust method allows analysis of constitutive units of grape skin proanthocyanidins, including some present in trace amounts, in a single injection, with a throughput of 6 samples per hour. 27775674 1 7 theme selective 143:151 arg1 method 162:167 A rapid, sensitive, and selective analysis method 119:167 A rapid, sensitive, and selective analysis method using ultra high performance liquid chromatography coupled with triple-quadrupole mass spectrometry (UHPLC-QqQ-MS) 119:282 A rapid, sensitive, and selective analysis method using ultra high performance liquid chromatography coupled with triple-quadrupole mass spectrometry (UHPLC-QqQ-MS) has been developed for the characterization and quantification of grape skin flavan-3-ols after acid-catalysed depolymerization in the presence of phloroglucinol (phloroglucinolysis). 27775674 3 8 theme different 851:859 arg1 cultivars 881:889 107 different red and white grape cultivars 847:889 107 different red and white grape cultivars grown under two conditions in the vineyard, irrigated or non-irrigated 847:960 This method was applied to a set of 214 grape skin samples from 107 different red and white grape cultivars grown under two conditions in the vineyard, irrigated or non-irrigated. 27775674 3 9 theme grape 823:827 arg1 samples 834:840 214 grape skin samples 819:840 214 grape skin samples from 107 different red and white grape cultivars grown under two conditions in the vineyard, irrigated or non-irrigated 819:960 This method was applied to a set of 214 grape skin samples from 107 different red and white grape cultivars grown under two conditions in the vineyard, irrigated or non-irrigated. 27775674 1 10 theme flavan-3-ols 361:372 arg1 characterization 311:326 characterization 311:326 characterization 311:326 A rapid, sensitive, and selective analysis method using ultra high performance liquid chromatography coupled with triple-quadrupole mass spectrometry (UHPLC-QqQ-MS) has been developed for the characterization and quantification of grape skin flavan-3-ols after acid-catalysed depolymerization in the presence of phloroglucinol (phloroglucinolysis). 27775674 1 10 theme flavan-3-ols 361:372 arg1 quantification 332:345 quantification 332:345 quantification 332:345 A rapid, sensitive, and selective analysis method using ultra high performance liquid chromatography coupled with triple-quadrupole mass spectrometry (UHPLC-QqQ-MS) has been developed for the characterization and quantification of grape skin flavan-3-ols after acid-catalysed depolymerization in the presence of phloroglucinol (phloroglucinolysis). 27775674 3 11 theme red 861:863 arg1 cultivars 881:889 107 different red and white grape cultivars 847:889 107 different red and white grape cultivars grown under two conditions in the vineyard, irrigated or non-irrigated 847:960 This method was applied to a set of 214 grape skin samples from 107 different red and white grape cultivars grown under two conditions in the vineyard, irrigated or non-irrigated. 27775674 5 12 theme composition 1201:1211 arg1 analysis 1182:1189 analysis 1182:1189 analysis of tannin composition 1182:1211 Moreover, these preliminary results suggest that analysis of tannin composition is relevant to investigate the genetic bases of grape response to drought. 27775674 2 13 theme MRM 563:565 arg1 mode 568:571 Multiple Reaction Monitoring (MRM) mode 533:571 Multiple Reaction Monitoring (MRM) mode 533:571 The compound detection being based on specific MS transitions in Multiple Reaction Monitoring (MRM) mode, this fast gradient robust method allows analysis of constitutive units of grape skin proanthocyanidins, including some present in trace amounts, in a single injection, with a throughput of 6 samples per hour. 27775674 4 14 theme metabolomics 1111:1122 arg1 studies 1124:1130 high-throughput and large-scale metabolomics studies 1079:1130 high-throughput and large-scale metabolomics studies 1079:1130 The results of triplicate analyses confirmed the robustness of the method, which was thus proven to be suitable for high-throughput and large-scale metabolomics studies. 27775674 1 15 theme acid-catalysed 380:393 arg1 depolymerization 395:410 acid-catalysed depolymerization 380:410 acid-catalysed depolymerization in the presence of phloroglucinol (phloroglucinolysis) 380:465 A rapid, sensitive, and selective analysis method using ultra high performance liquid chromatography coupled with triple-quadrupole mass spectrometry (UHPLC-QqQ-MS) has been developed for the characterization and quantification of grape skin flavan-3-ols after acid-catalysed depolymerization in the presence of phloroglucinol (phloroglucinolysis). 27775674 2 16 theme proanthocyanidins 659:675 arg1 units 639:643 constitutive units 626:643 constitutive units of grape skin proanthocyanidins 626:675 The compound detection being based on specific MS transitions in Multiple Reaction Monitoring (MRM) mode, this fast gradient robust method allows analysis of constitutive units of grape skin proanthocyanidins, including some present in trace amounts, in a single injection, with a throughput of 6 samples per hour. 27775674 4 17 theme method 1030:1035 arg1 robustness 1012:1021 the robustness 1008:1021 the robustness 1008:1021 The results of triplicate analyses confirmed the robustness of the method, which was thus proven to be suitable for high-throughput and large-scale metabolomics studies. 27775674 4 17 theme method 1030:1035 arg1 suitable 1066:1073 suitable 1066:1073 suitable 1066:1073 The results of triplicate analyses confirmed the robustness of the method, which was thus proven to be suitable for high-throughput and large-scale metabolomics studies. 27775674 2 18 theme samples 765:771 arg1 throughput 749:758 a throughput 747:758 a throughput of 6 samples per hour 747:780 The compound detection being based on specific MS transitions in Multiple Reaction Monitoring (MRM) mode, this fast gradient robust method allows analysis of constitutive units of grape skin proanthocyanidins, including some present in trace amounts, in a single injection, with a throughput of 6 samples per hour. 27775674 1 19 theme analysis 153:160 arg1 method 162:167 A rapid, sensitive, and selective analysis method 119:167 A rapid, sensitive, and selective analysis method using ultra high performance liquid chromatography coupled with triple-quadrupole mass spectrometry (UHPLC-QqQ-MS) 119:282 A rapid, sensitive, and selective analysis method using ultra high performance liquid chromatography coupled with triple-quadrupole mass spectrometry (UHPLC-QqQ-MS) has been developed for the characterization and quantification of grape skin flavan-3-ols after acid-catalysed depolymerization in the presence of phloroglucinol (phloroglucinolysis). 27775674 0 20 theme Chemical 92:99 arg1 Depolymerization 101:116 Chemical Depolymerization 92:116 Chemical Depolymerization 92:116 A Fast and Robust UHPLC-MRM-MS Method to Characterize and Quantify Grape Skin Tannins after Chemical Depolymerization. 27775674 2 21 theme skin 654:657 arg1 proanthocyanidins 659:675 grape skin proanthocyanidins 648:675 grape skin proanthocyanidins 648:675 The compound detection being based on specific MS transitions in Multiple Reaction Monitoring (MRM) mode, this fast gradient robust method allows analysis of constitutive units of grape skin proanthocyanidins, including some present in trace amounts, in a single injection, with a throughput of 6 samples per hour. 27775674 3 22 theme grape 875:879 arg1 cultivars 881:889 107 different red and white grape cultivars 847:889 107 different red and white grape cultivars grown under two conditions in the vineyard, irrigated or non-irrigated 847:960 This method was applied to a set of 214 grape skin samples from 107 different red and white grape cultivars grown under two conditions in the vineyard, irrigated or non-irrigated. 27775674 0 23 theme Fast 2:5 arg1 Method 31:36 A Fast and Robust UHPLC-MRM-MS Method 0:36 A Fast and Robust UHPLC-MRM-MS Method 0:36 A Fast and Robust UHPLC-MRM-MS Method to Characterize and Quantify Grape Skin Tannins after Chemical Depolymerization. 27775674 1 24 dep characterization 311:326 arg1 the 307:309 the 307:309 the 307:309 A rapid, sensitive, and selective analysis method using ultra high performance liquid chromatography coupled with triple-quadrupole mass spectrometry (UHPLC-QqQ-MS) has been developed for the characterization and quantification of grape skin flavan-3-ols after acid-catalysed depolymerization in the presence of phloroglucinol (phloroglucinolysis). 27775674 2 25 theme grape 648:652 arg1 proanthocyanidins 659:675 grape skin proanthocyanidins 648:675 grape skin proanthocyanidins 648:675 The compound detection being based on specific MS transitions in Multiple Reaction Monitoring (MRM) mode, this fast gradient robust method allows analysis of constitutive units of grape skin proanthocyanidins, including some present in trace amounts, in a single injection, with a throughput of 6 samples per hour. 27775674 2 26 theme trace 704:708 arg1 amounts 710:716 trace amounts 704:716 trace amounts 704:716 The compound detection being based on specific MS transitions in Multiple Reaction Monitoring (MRM) mode, this fast gradient robust method allows analysis of constitutive units of grape skin proanthocyanidins, including some present in trace amounts, in a single injection, with a throughput of 6 samples per hour. 27775674 1 27 theme ultra 175:179 arg1 chromatography 205:218 ultra high performance liquid chromatography 175:218 ultra high performance liquid chromatography coupled with triple-quadrupole mass spectrometry (UHPLC-QqQ-MS) 175:282 A rapid, sensitive, and selective analysis method using ultra high performance liquid chromatography coupled with triple-quadrupole mass spectrometry (UHPLC-QqQ-MS) has been developed for the characterization and quantification of grape skin flavan-3-ols after acid-catalysed depolymerization in the presence of phloroglucinol (phloroglucinolysis). 27775674 0 28 theme Robust 11:16 arg1 Method 31:36 A Fast and Robust UHPLC-MRM-MS Method 0:36 A Fast and Robust UHPLC-MRM-MS Method 0:36 A Fast and Robust UHPLC-MRM-MS Method to Characterize and Quantify Grape Skin Tannins after Chemical Depolymerization. 27775674 2 29 theme fast 579:582 arg1 method 600:605 this fast gradient robust method 574:605 this fast gradient robust method 574:605 The compound detection being based on specific MS transitions in Multiple Reaction Monitoring (MRM) mode, this fast gradient robust method allows analysis of constitutive units of grape skin proanthocyanidins, including some present in trace amounts, in a single injection, with a throughput of 6 samples per hour. 27775674 4 30 theme triplicate 978:987 arg1 analyses 989:996 triplicate analyses 978:996 triplicate analyses 978:996 The results of triplicate analyses confirmed the robustness of the method, which was thus proven to be suitable for high-throughput and large-scale metabolomics studies. 27775674 1 31 theme high 181:184 arg1 chromatography 205:218 ultra high performance liquid chromatography 175:218 ultra high performance liquid chromatography coupled with triple-quadrupole mass spectrometry (UHPLC-QqQ-MS) 175:282 A rapid, sensitive, and selective analysis method using ultra high performance liquid chromatography coupled with triple-quadrupole mass spectrometry (UHPLC-QqQ-MS) has been developed for the characterization and quantification of grape skin flavan-3-ols after acid-catalysed depolymerization in the presence of phloroglucinol (phloroglucinolysis). 27775674 2 32 from amounts 710:716 arg1 present 693:699 present 693:699 present 693:699 The compound detection being based on specific MS transitions in Multiple Reaction Monitoring (MRM) mode, this fast gradient robust method allows analysis of constitutive units of grape skin proanthocyanidins, including some present in trace amounts, in a single injection, with a throughput of 6 samples per hour. 27775674 1 33 theme performance 186:196 arg1 chromatography 205:218 ultra high performance liquid chromatography 175:218 ultra high performance liquid chromatography coupled with triple-quadrupole mass spectrometry (UHPLC-QqQ-MS) 175:282 A rapid, sensitive, and selective analysis method using ultra high performance liquid chromatography coupled with triple-quadrupole mass spectrometry (UHPLC-QqQ-MS) has been developed for the characterization and quantification of grape skin flavan-3-ols after acid-catalysed depolymerization in the presence of phloroglucinol (phloroglucinolysis). 27775674 2 34 theme MS 515:516 arg1 transitions 518:528 specific MS transitions 506:528 specific MS transitions in Multiple Reaction Monitoring (MRM) mode 506:571 The compound detection being based on specific MS transitions in Multiple Reaction Monitoring (MRM) mode, this fast gradient robust method allows analysis of constitutive units of grape skin proanthocyanidins, including some present in trace amounts, in a single injection, with a throughput of 6 samples per hour. 27775674 4 35 theme large-scale 1099:1109 arg1 studies 1124:1130 high-throughput and large-scale metabolomics studies 1079:1130 high-throughput and large-scale metabolomics studies 1079:1130 The results of triplicate analyses confirmed the robustness of the method, which was thus proven to be suitable for high-throughput and large-scale metabolomics studies. 27775674 2 36 from transitions 518:528 arg1 mode 568:571 Multiple Reaction Monitoring (MRM) mode 533:571 Multiple Reaction Monitoring (MRM) mode 533:571 The compound detection being based on specific MS transitions in Multiple Reaction Monitoring (MRM) mode, this fast gradient robust method allows analysis of constitutive units of grape skin proanthocyanidins, including some present in trace amounts, in a single injection, with a throughput of 6 samples per hour. 27775674 4 37 theme high-throughput 1079:1093 arg1 studies 1124:1130 high-throughput and large-scale metabolomics studies 1079:1130 high-throughput and large-scale metabolomics studies 1079:1130 The results of triplicate analyses confirmed the robustness of the method, which was thus proven to be suitable for high-throughput and large-scale metabolomics studies. 27775674 1 38 theme liquid 198:203 arg1 chromatography 205:218 ultra high performance liquid chromatography 175:218 ultra high performance liquid chromatography coupled with triple-quadrupole mass spectrometry (UHPLC-QqQ-MS) 175:282 A rapid, sensitive, and selective analysis method using ultra high performance liquid chromatography coupled with triple-quadrupole mass spectrometry (UHPLC-QqQ-MS) has been developed for the characterization and quantification of grape skin flavan-3-ols after acid-catalysed depolymerization in the presence of phloroglucinol (phloroglucinolysis). 27775674 0 39 theme UHPLC-MRM-MS 18:29 arg1 Method 31:36 A Fast and Robust UHPLC-MRM-MS Method 0:36 A Fast and Robust UHPLC-MRM-MS Method 0:36 A Fast and Robust UHPLC-MRM-MS Method to Characterize and Quantify Grape Skin Tannins after Chemical Depolymerization. 27775674 2 40 theme specific 506:513 arg1 transitions 518:528 specific MS transitions 506:528 specific MS transitions in Multiple Reaction Monitoring (MRM) mode 506:571 The compound detection being based on specific MS transitions in Multiple Reaction Monitoring (MRM) mode, this fast gradient robust method allows analysis of constitutive units of grape skin proanthocyanidins, including some present in trace amounts, in a single injection, with a throughput of 6 samples per hour. 27775674 5 41 theme tannin 1194:1199 arg1 composition 1201:1211 tannin composition 1194:1211 tannin composition 1194:1211 Moreover, these preliminary results suggest that analysis of tannin composition is relevant to investigate the genetic bases of grape response to drought. 27775674 2 42 theme compound 472:479 arg1 detection 481:489 The compound detection 468:489 The compound detection 468:489 The compound detection being based on specific MS transitions in Multiple Reaction Monitoring (MRM) mode, this fast gradient robust method allows analysis of constitutive units of grape skin proanthocyanidins, including some present in trace amounts, in a single injection, with a throughput of 6 samples per hour. 27775674 2 43 theme Monitoring 551:560 arg1 mode 568:571 Multiple Reaction Monitoring (MRM) mode 533:571 Multiple Reaction Monitoring (MRM) mode 533:571 The compound detection being based on specific MS transitions in Multiple Reaction Monitoring (MRM) mode, this fast gradient robust method allows analysis of constitutive units of grape skin proanthocyanidins, including some present in trace amounts, in a single injection, with a throughput of 6 samples per hour. 27775674 1 44 theme phloroglucinol 431:444 arg1 presence 419:426 the presence 415:426 the presence of phloroglucinol (phloroglucinolysis) 415:465 A rapid, sensitive, and selective analysis method using ultra high performance liquid chromatography coupled with triple-quadrupole mass spectrometry (UHPLC-QqQ-MS) has been developed for the characterization and quantification of grape skin flavan-3-ols after acid-catalysed depolymerization in the presence of phloroglucinol (phloroglucinolysis). 27775674 2 45 theme single 724:729 arg1 injection 731:739 a single injection 722:739 a single injection 722:739 The compound detection being based on specific MS transitions in Multiple Reaction Monitoring (MRM) mode, this fast gradient robust method allows analysis of constitutive units of grape skin proanthocyanidins, including some present in trace amounts, in a single injection, with a throughput of 6 samples per hour. 27775674 4 46 theme analyses 989:996 arg1 results 967:973 The results 963:973 The results of triplicate analyses 963:996 The results of triplicate analyses confirmed the robustness of the method, which was thus proven to be suitable for high-throughput and large-scale metabolomics studies. 27775674 3 47 from set 812:814 arg1 cultivars 881:889 107 different red and white grape cultivars 847:889 107 different red and white grape cultivars grown under two conditions in the vineyard, irrigated or non-irrigated 847:960 This method was applied to a set of 214 grape skin samples from 107 different red and white grape cultivars grown under two conditions in the vineyard, irrigated or non-irrigated. 27775674 5 48 theme response 1267:1274 arg1 bases 1252:1256 the genetic bases 1240:1256 the genetic bases of grape response to drought 1240:1285 Moreover, these preliminary results suggest that analysis of tannin composition is relevant to investigate the genetic bases of grape response to drought. 27775674 5 49 theme preliminary 1149:1159 arg1 results 1161:1167 these preliminary results 1143:1167 these preliminary results 1143:1167 Moreover, these preliminary results suggest that analysis of tannin composition is relevant to investigate the genetic bases of grape response to drought. 27775674 2 50 theme robust 593:598 arg1 method 600:605 this fast gradient robust method 574:605 this fast gradient robust method 574:605 The compound detection being based on specific MS transitions in Multiple Reaction Monitoring (MRM) mode, this fast gradient robust method allows analysis of constitutive units of grape skin proanthocyanidins, including some present in trace amounts, in a single injection, with a throughput of 6 samples per hour. 27775674 1 51 theme rapid 121:125 arg1 method 162:167 A rapid, sensitive, and selective analysis method 119:167 A rapid, sensitive, and selective analysis method using ultra high performance liquid chromatography coupled with triple-quadrupole mass spectrometry (UHPLC-QqQ-MS) 119:282 A rapid, sensitive, and selective analysis method using ultra high performance liquid chromatography coupled with triple-quadrupole mass spectrometry (UHPLC-QqQ-MS) has been developed for the characterization and quantification of grape skin flavan-3-ols after acid-catalysed depolymerization in the presence of phloroglucinol (phloroglucinolysis). 27775674 2 52 theme gradient 584:591 arg1 method 600:605 this fast gradient robust method 574:605 this fast gradient robust method 574:605 The compound detection being based on specific MS transitions in Multiple Reaction Monitoring (MRM) mode, this fast gradient robust method allows analysis of constitutive units of grape skin proanthocyanidins, including some present in trace amounts, in a single injection, with a throughput of 6 samples per hour. 27775674 3 53 from cultivars 881:889 arg1 samples 834:840 214 grape skin samples 819:840 214 grape skin samples from 107 different red and white grape cultivars grown under two conditions in the vineyard, irrigated or non-irrigated 819:960 This method was applied to a set of 214 grape skin samples from 107 different red and white grape cultivars grown under two conditions in the vineyard, irrigated or non-irrigated. 27775674 3 53 from cultivars 881:889 arg1 set 812:814 a set 810:814 a set of 214 grape skin samples from 107 different red and white grape cultivars grown under two conditions in the vineyard, irrigated or non-irrigated 810:960 This method was applied to a set of 214 grape skin samples from 107 different red and white grape cultivars grown under two conditions in the vineyard, irrigated or non-irrigated. 27775674 3 54 theme skin 829:832 arg1 samples 834:840 214 grape skin samples 819:840 214 grape skin samples from 107 different red and white grape cultivars grown under two conditions in the vineyard, irrigated or non-irrigated 819:960 This method was applied to a set of 214 grape skin samples from 107 different red and white grape cultivars grown under two conditions in the vineyard, irrigated or non-irrigated. 27775674 2 55 from present 693:699 arg1 amounts 710:716 trace amounts 704:716 trace amounts 704:716 The compound detection being based on specific MS transitions in Multiple Reaction Monitoring (MRM) mode, this fast gradient robust method allows analysis of constitutive units of grape skin proanthocyanidins, including some present in trace amounts, in a single injection, with a throughput of 6 samples per hour. 27775674 2 56 theme Reaction 542:549 arg1 mode 568:571 Multiple Reaction Monitoring (MRM) mode 533:571 Multiple Reaction Monitoring (MRM) mode 533:571 The compound detection being based on specific MS transitions in Multiple Reaction Monitoring (MRM) mode, this fast gradient robust method allows analysis of constitutive units of grape skin proanthocyanidins, including some present in trace amounts, in a single injection, with a throughput of 6 samples per hour. 27775674 5 57 theme grape 1261:1265 arg1 response 1267:1274 grape response 1261:1274 grape response to drought 1261:1285 Moreover, these preliminary results suggest that analysis of tannin composition is relevant to investigate the genetic bases of grape response to drought. 27775674 1 58 theme sensitive 128:136 arg1 method 162:167 A rapid, sensitive, and selective analysis method 119:167 A rapid, sensitive, and selective analysis method using ultra high performance liquid chromatography coupled with triple-quadrupole mass spectrometry (UHPLC-QqQ-MS) 119:282 A rapid, sensitive, and selective analysis method using ultra high performance liquid chromatography coupled with triple-quadrupole mass spectrometry (UHPLC-QqQ-MS) has been developed for the characterization and quantification of grape skin flavan-3-ols after acid-catalysed depolymerization in the presence of phloroglucinol (phloroglucinolysis). 27775674 3 59 theme samples 834:840 arg1 samples 834:840 214 grape skin samples 819:840 214 grape skin samples from 107 different red and white grape cultivars grown under two conditions in the vineyard, irrigated or non-irrigated 819:960 This method was applied to a set of 214 grape skin samples from 107 different red and white grape cultivars grown under two conditions in the vineyard, irrigated or non-irrigated. 27775674 3 59 theme samples 834:840 arg1 set 812:814 a set 810:814 a set of 214 grape skin samples from 107 different red and white grape cultivars grown under two conditions in the vineyard, irrigated or non-irrigated 810:960 This method was applied to a set of 214 grape skin samples from 107 different red and white grape cultivars grown under two conditions in the vineyard, irrigated or non-irrigated. 27775674 1 60 theme triple-quadrupole 233:249 arg1 UHPLC-QqQ-MS 270:281 UHPLC-QqQ-MS 270:281 UHPLC-QqQ-MS 270:281 A rapid, sensitive, and selective analysis method using ultra high performance liquid chromatography coupled with triple-quadrupole mass spectrometry (UHPLC-QqQ-MS) has been developed for the characterization and quantification of grape skin flavan-3-ols after acid-catalysed depolymerization in the presence of phloroglucinol (phloroglucinolysis). 27775674 1 60 theme triple-quadrupole 233:249 arg1 spectrometry 256:267 triple-quadrupole mass spectrometry 233:267 triple-quadrupole mass spectrometry (UHPLC-QqQ-MS) 233:282 A rapid, sensitive, and selective analysis method using ultra high performance liquid chromatography coupled with triple-quadrupole mass spectrometry (UHPLC-QqQ-MS) has been developed for the characterization and quantification of grape skin flavan-3-ols after acid-catalysed depolymerization in the presence of phloroglucinol (phloroglucinolysis). 27775674 2 61 theme Multiple 533:540 arg1 mode 568:571 Multiple Reaction Monitoring (MRM) mode 533:571 Multiple Reaction Monitoring (MRM) mode 533:571 The compound detection being based on specific MS transitions in Multiple Reaction Monitoring (MRM) mode, this fast gradient robust method allows analysis of constitutive units of grape skin proanthocyanidins, including some present in trace amounts, in a single injection, with a throughput of 6 samples per hour. 27775674 1 62 from depolymerization 395:410 arg1 presence 419:426 the presence 415:426 the presence of phloroglucinol (phloroglucinolysis) 415:465 A rapid, sensitive, and selective analysis method using ultra high performance liquid chromatography coupled with triple-quadrupole mass spectrometry (UHPLC-QqQ-MS) has been developed for the characterization and quantification of grape skin flavan-3-ols after acid-catalysed depolymerization in the presence of phloroglucinol (phloroglucinolysis). 27775674 5 63 theme genetic 1244:1250 arg1 bases 1252:1256 the genetic bases 1240:1256 the genetic bases of grape response to drought 1240:1285 Moreover, these preliminary results suggest that analysis of tannin composition is relevant to investigate the genetic bases of grape response to drought. 27775674 1 64 theme mass 251:254 arg1 UHPLC-QqQ-MS 270:281 UHPLC-QqQ-MS 270:281 UHPLC-QqQ-MS 270:281 A rapid, sensitive, and selective analysis method using ultra high performance liquid chromatography coupled with triple-quadrupole mass spectrometry (UHPLC-QqQ-MS) has been developed for the characterization and quantification of grape skin flavan-3-ols after acid-catalysed depolymerization in the presence of phloroglucinol (phloroglucinolysis). 27775674 1 64 theme mass 251:254 arg1 spectrometry 256:267 triple-quadrupole mass spectrometry 233:267 triple-quadrupole mass spectrometry (UHPLC-QqQ-MS) 233:282 A rapid, sensitive, and selective analysis method using ultra high performance liquid chromatography coupled with triple-quadrupole mass spectrometry (UHPLC-QqQ-MS) has been developed for the characterization and quantification of grape skin flavan-3-ols after acid-catalysed depolymerization in the presence of phloroglucinol (phloroglucinolysis). 27208284 10 0 from activity 1518:1525 arg1 Arabidopsis 1572:1582 developing Arabidopsis 1561:1582 developing Arabidopsis 1561:1582 We propose that posttranslational modification of TCP14/15 by SPY inhibits their proteolysis and that the accumulated proteins promote the activity of the CK phosphorelay cascade in developing Arabidopsis leaves and flowers. 27208284 10 1 theme cascade 1550:1556 arg1 activity 1518:1525 the activity 1514:1525 the activity of the CK phosphorelay cascade in developing Arabidopsis 1514:1582 We propose that posttranslational modification of TCP14/15 by SPY inhibits their proteolysis and that the accumulated proteins promote the activity of the CK phosphorelay cascade in developing Arabidopsis leaves and flowers. 27208284 8 2 theme higher 1208:1213 arg1 levels 1218:1223 higher CK levels 1208:1223 higher CK levels 1208:1223 The increased CK activity in TCP14/15-overexpressing flowers resulted from increased sensitivity to the hormone and not from higher CK levels. 27208284 5 3 theme TCP14 721:725 arg1 stability 727:735 TCP14 stability 721:735 TCP14 stability 721:735 We show that SPY activity is required for TCP14 stability. 27208284 7 4 theme misexpression 1020:1032 arg1 phenotypes 1034:1043 all TCP14 misexpression phenotypes 1010:1043 all TCP14 misexpression phenotypes 1010:1043 TCP14 proteolysis in spy-3 suppressed all TCP14 misexpression phenotypes, including the enhanced CK responses. 27208284 7 4 theme misexpression 1020:1032 arg1 responses 1072:1080 the enhanced CK responses 1056:1080 the enhanced CK responses 1056:1080 TCP14 proteolysis in spy-3 suppressed all TCP14 misexpression phenotypes, including the enhanced CK responses. 27208284 8 5 theme increased 1158:1166 arg1 sensitivity 1168:1178 increased sensitivity 1158:1178 increased sensitivity to the hormone 1158:1193 The increased CK activity in TCP14/15-overexpressing flowers resulted from increased sensitivity to the hormone and not from higher CK levels. 27208284 2 6 from effect 422:427 arg1 fate 440:443 protein fate 432:443 protein fate 432:443 While SPY has been shown to suppress gibberellin signaling and to promote cytokinin (CK) responses, its catalytic OGT activity was never demonstrated and its effect on protein fate is not known. 27208284 6 7 theme OGT 763:765 arg1 SPY 777:779 SPY 777:779 SPY (spy-3) 777:787 Mutation in the putative OGT domain of SPY (spy-3) stimulated TCP14 proteolysis by the 26S proteasome, which was reversed by mutation in CULLIN1 (CUL1), suggesting a role for SKP, CUL1, F-box E3 ubiquitin ligase in TCP14 proteolysis. 27208284 6 7 theme OGT 763:765 arg1 domain 767:772 the putative OGT domain 750:772 the putative OGT domain of SPY (spy-3) 750:787 Mutation in the putative OGT domain of SPY (spy-3) stimulated TCP14 proteolysis by the 26S proteasome, which was reversed by mutation in CULLIN1 (CUL1), suggesting a role for SKP, CUL1, F-box E3 ubiquitin ligase in TCP14 proteolysis. 27208284 6 8 theme putative 754:761 arg1 SPY 777:779 SPY 777:779 SPY (spy-3) 777:787 Mutation in the putative OGT domain of SPY (spy-3) stimulated TCP14 proteolysis by the 26S proteasome, which was reversed by mutation in CULLIN1 (CUL1), suggesting a role for SKP, CUL1, F-box E3 ubiquitin ligase in TCP14 proteolysis. 27208284 6 8 theme putative 754:761 arg1 domain 767:772 the putative OGT domain 750:772 the putative OGT domain of SPY (spy-3) 750:787 Mutation in the putative OGT domain of SPY (spy-3) stimulated TCP14 proteolysis by the 26S proteasome, which was reversed by mutation in CULLIN1 (CUL1), suggesting a role for SKP, CUL1, F-box E3 ubiquitin ligase in TCP14 proteolysis. 27208284 8 9 theme CK 1215:1216 arg1 levels 1218:1223 higher CK levels 1208:1223 higher CK levels 1208:1223 The increased CK activity in TCP14/15-overexpressing flowers resulted from increased sensitivity to the hormone and not from higher CK levels. 27208284 5 10 theme SPY 692:694 arg1 activity 696:703 SPY activity 692:703 SPY activity 692:703 We show that SPY activity is required for TCP14 stability. 27208284 6 11 theme 26S 825:827 arg1 proteasome 829:838 the 26S proteasome 821:838 the 26S proteasome 821:838 Mutation in the putative OGT domain of SPY (spy-3) stimulated TCP14 proteolysis by the 26S proteasome, which was reversed by mutation in CULLIN1 (CUL1), suggesting a role for SKP, CUL1, F-box E3 ubiquitin ligase in TCP14 proteolysis. 27208284 8 12 theme CK 1097:1098 arg1 activity 1100:1107 The increased CK activity 1083:1107 The increased CK activity in TCP14/15-overexpressing flowers 1083:1142 The increased CK activity in TCP14/15-overexpressing flowers resulted from increased sensitivity to the hormone and not from higher CK levels. 27208284 2 13 theme OGT 378:380 arg1 activity 382:389 its catalytic OGT activity 364:389 its catalytic OGT activity 364:389 While SPY has been shown to suppress gibberellin signaling and to promote cytokinin (CK) responses, its catalytic OGT activity was never demonstrated and its effect on protein fate is not known. 27208284 9 14 theme early 1350:1354 arg1 steps 1356:1360 early steps 1350:1360 early steps in CK signaling 1350:1376 TCP15 overexpression enhanced the response of the CK-induced synthetic promoter pTCS to CK, suggesting that TCP14/15 affect early steps in CK signaling. 27208284 10 15 theme developing 1561:1570 arg1 Arabidopsis 1572:1582 developing Arabidopsis 1561:1582 developing Arabidopsis 1561:1582 We propose that posttranslational modification of TCP14/15 by SPY inhibits their proteolysis and that the accumulated proteins promote the activity of the CK phosphorelay cascade in developing Arabidopsis leaves and flowers. 27208284 10 16 theme posttranslational 1395:1411 arg1 modification 1413:1424 posttranslational modification 1395:1424 posttranslational modification of TCP14/15 by SPY 1395:1443 We propose that posttranslational modification of TCP14/15 by SPY inhibits their proteolysis and that the accumulated proteins promote the activity of the CK phosphorelay cascade in developing Arabidopsis leaves and flowers. 27208284 2 17 theme catalytic 368:376 arg1 activity 382:389 its catalytic OGT activity 364:389 its catalytic OGT activity 364:389 While SPY has been shown to suppress gibberellin signaling and to promote cytokinin (CK) responses, its catalytic OGT activity was never demonstrated and its effect on protein fate is not known. 27208284 0 18 theme Putative 4:11 arg1 Transferase 42:52 The Putative O-Linked N-Acetylglucosamine Transferase 0:52 The Putative O-Linked N-Acetylglucosamine Transferase 0:52 The Putative O-Linked N-Acetylglucosamine Transferase SPINDLY Inhibits Class I TCP Proteolysis to Promote Sensitivity to Cytokinin. 27208284 7 19 theme TCP14 972:976 arg1 proteolysis 978:988 TCP14 proteolysis 972:988 TCP14 proteolysis in spy-3 972:997 TCP14 proteolysis in spy-3 suppressed all TCP14 misexpression phenotypes, including the enhanced CK responses. 27208284 10 20 dep promote 1506:1512 arg1 flowers 1595:1601 flowers 1595:1601 flowers 1595:1601 We propose that posttranslational modification of TCP14/15 by SPY inhibits their proteolysis and that the accumulated proteins promote the activity of the CK phosphorelay cascade in developing Arabidopsis leaves and flowers. 27208284 10 20 dep promote 1506:1512 arg1 leaves 1584:1589 leaves 1584:1589 leaves 1584:1589 We propose that posttranslational modification of TCP14/15 by SPY inhibits their proteolysis and that the accumulated proteins promote the activity of the CK phosphorelay cascade in developing Arabidopsis leaves and flowers. 27208284 9 21 theme TCP15 1226:1230 arg1 overexpression 1232:1245 TCP15 overexpression 1226:1245 TCP15 overexpression 1226:1245 TCP15 overexpression enhanced the response of the CK-induced synthetic promoter pTCS to CK, suggesting that TCP14/15 affect early steps in CK signaling. 27208284 9 22 theme CK 1365:1366 arg1 signaling 1368:1376 CK signaling 1365:1376 CK signaling 1365:1376 TCP15 overexpression enhanced the response of the CK-induced synthetic promoter pTCS to CK, suggesting that TCP14/15 affect early steps in CK signaling. 27208284 10 23 theme phosphorelay 1537:1548 arg1 cascade 1550:1556 the CK phosphorelay cascade 1530:1556 the CK phosphorelay cascade 1530:1556 We propose that posttranslational modification of TCP14/15 by SPY inhibits their proteolysis and that the accumulated proteins promote the activity of the CK phosphorelay cascade in developing Arabidopsis leaves and flowers. 27208284 6 24 from role 904:907 arg1 proteolysis 959:969 TCP14 proteolysis 953:969 TCP14 proteolysis 953:969 Mutation in the putative OGT domain of SPY (spy-3) stimulated TCP14 proteolysis by the 26S proteasome, which was reversed by mutation in CULLIN1 (CUL1), suggesting a role for SKP, CUL1, F-box E3 ubiquitin ligase in TCP14 proteolysis. 27208284 1 25 link O-linked 216:223 arg1 transferase 245:255 O-linked N-acetylglucosamine transferase 216:255 O-linked N-acetylglucosamine transferase (OGT) 216:261 Arabidopsis (Arabidopsis thaliana) SPINDLY (SPY) is a putative serine and threonine O-linked N-acetylglucosamine transferase (OGT). 27208284 1 25 link O-linked 216:223 arg1 OGT 258:260 OGT 258:260 OGT 258:260 Arabidopsis (Arabidopsis thaliana) SPINDLY (SPY) is a putative serine and threonine O-linked N-acetylglucosamine transferase (OGT). 27208284 2 26 theme gibberellin 301:311 arg1 signaling 313:321 gibberellin signaling 301:321 gibberellin signaling 301:321 While SPY has been shown to suppress gibberellin signaling and to promote cytokinin (CK) responses, its catalytic OGT activity was never demonstrated and its effect on protein fate is not known. 27208284 0 27 theme N-Acetylglucosamine 22:40 arg1 Transferase 42:52 The Putative O-Linked N-Acetylglucosamine Transferase 0:52 The Putative O-Linked N-Acetylglucosamine Transferase 0:52 The Putative O-Linked N-Acetylglucosamine Transferase SPINDLY Inhibits Class I TCP Proteolysis to Promote Sensitivity to Cytokinin. 27208284 7 28 from proteolysis 978:988 arg1 spy-3 993:997 spy-3 993:997 spy-3 993:997 TCP14 proteolysis in spy-3 suppressed all TCP14 misexpression phenotypes, including the enhanced CK responses. 27208284 10 29 theme CK 1534:1535 arg1 cascade 1550:1556 the CK phosphorelay cascade 1530:1556 the CK phosphorelay cascade 1530:1556 We propose that posttranslational modification of TCP14/15 by SPY inhibits their proteolysis and that the accumulated proteins promote the activity of the CK phosphorelay cascade in developing Arabidopsis leaves and flowers. 27208284 10 30 theme accumulated 1485:1495 arg1 proteins 1497:1504 the accumulated proteins 1481:1504 the accumulated proteins 1481:1504 We propose that posttranslational modification of TCP14/15 by SPY inhibits their proteolysis and that the accumulated proteins promote the activity of the CK phosphorelay cascade in developing Arabidopsis leaves and flowers. 27208284 1 31 theme putative 186:193 arg1 serine 195:200 serine 195:200 serine 195:200 Arabidopsis (Arabidopsis thaliana) SPINDLY (SPY) is a putative serine and threonine O-linked N-acetylglucosamine transferase (OGT). 27208284 1 31 theme putative 186:193 arg1 SPINDLY 167:173 Arabidopsis (Arabidopsis thaliana) SPINDLY 132:173 Arabidopsis (Arabidopsis thaliana) SPINDLY (SPY) 132:179 Arabidopsis (Arabidopsis thaliana) SPINDLY (SPY) is a putative serine and threonine O-linked N-acetylglucosamine transferase (OGT). 27208284 0 32 theme O-Linked 13:20 arg1 Transferase 42:52 The Putative O-Linked N-Acetylglucosamine Transferase 0:52 The Putative O-Linked N-Acetylglucosamine Transferase 0:52 The Putative O-Linked N-Acetylglucosamine Transferase SPINDLY Inhibits Class I TCP Proteolysis to Promote Sensitivity to Cytokinin. 27208284 6 33 theme ubiquitin 933:941 arg1 ligase 943:948 F-box E3 ubiquitin ligase 924:948 F-box E3 ubiquitin ligase 924:948 Mutation in the putative OGT domain of SPY (spy-3) stimulated TCP14 proteolysis by the 26S proteasome, which was reversed by mutation in CULLIN1 (CUL1), suggesting a role for SKP, CUL1, F-box E3 ubiquitin ligase in TCP14 proteolysis. 27208284 6 33 theme ubiquitin 933:941 arg1 SKP 913:915 SKP 913:915 SKP 913:915 Mutation in the putative OGT domain of SPY (spy-3) stimulated TCP14 proteolysis by the 26S proteasome, which was reversed by mutation in CULLIN1 (CUL1), suggesting a role for SKP, CUL1, F-box E3 ubiquitin ligase in TCP14 proteolysis. 27208284 8 34 theme TCP14/15-overexpressing 1112:1134 arg1 flowers 1136:1142 TCP14/15-overexpressing flowers 1112:1142 TCP14/15-overexpressing flowers 1112:1142 The increased CK activity in TCP14/15-overexpressing flowers resulted from increased sensitivity to the hormone and not from higher CK levels. 27208284 4 35 theme CK 665:666 arg1 responses 668:676 CK responses 665:676 CK responses 665:676 Here, we aimed to identify how SPY regulates TCP14/15 activities and how these TCPs promote CK responses. 27208284 6 36 theme E3 930:931 arg1 ligase 943:948 F-box E3 ubiquitin ligase 924:948 F-box E3 ubiquitin ligase 924:948 Mutation in the putative OGT domain of SPY (spy-3) stimulated TCP14 proteolysis by the 26S proteasome, which was reversed by mutation in CULLIN1 (CUL1), suggesting a role for SKP, CUL1, F-box E3 ubiquitin ligase in TCP14 proteolysis. 27208284 6 36 theme E3 930:931 arg1 SKP 913:915 SKP 913:915 SKP 913:915 Mutation in the putative OGT domain of SPY (spy-3) stimulated TCP14 proteolysis by the 26S proteasome, which was reversed by mutation in CULLIN1 (CUL1), suggesting a role for SKP, CUL1, F-box E3 ubiquitin ligase in TCP14 proteolysis. 27208284 4 37 theme TCP14/15 618:625 arg1 activities 627:636 TCP14/15 activities 618:636 TCP14/15 activities 618:636 Here, we aimed to identify how SPY regulates TCP14/15 activities and how these TCPs promote CK responses. 27208284 6 38 dep stimulated 789:798 arg1 reversed 851:858 reversed 851:858 reversed 851:858 Mutation in the putative OGT domain of SPY (spy-3) stimulated TCP14 proteolysis by the 26S proteasome, which was reversed by mutation in CULLIN1 (CUL1), suggesting a role for SKP, CUL1, F-box E3 ubiquitin ligase in TCP14 proteolysis. 27208284 9 39 theme pTCS 1306:1309 arg1 response 1260:1267 the response 1256:1267 the response of the CK-induced synthetic promoter pTCS to CK 1256:1315 TCP15 overexpression enhanced the response of the CK-induced synthetic promoter pTCS to CK, suggesting that TCP14/15 affect early steps in CK signaling. 27208284 7 40 theme enhanced 1060:1067 arg1 responses 1072:1080 the enhanced CK responses 1056:1080 the enhanced CK responses 1056:1080 TCP14 proteolysis in spy-3 suppressed all TCP14 misexpression phenotypes, including the enhanced CK responses. 27208284 6 41 theme F-box 924:928 arg1 ligase 943:948 F-box E3 ubiquitin ligase 924:948 F-box E3 ubiquitin ligase 924:948 Mutation in the putative OGT domain of SPY (spy-3) stimulated TCP14 proteolysis by the 26S proteasome, which was reversed by mutation in CULLIN1 (CUL1), suggesting a role for SKP, CUL1, F-box E3 ubiquitin ligase in TCP14 proteolysis. 27208284 6 41 theme F-box 924:928 arg1 SKP 913:915 SKP 913:915 SKP 913:915 Mutation in the putative OGT domain of SPY (spy-3) stimulated TCP14 proteolysis by the 26S proteasome, which was reversed by mutation in CULLIN1 (CUL1), suggesting a role for SKP, CUL1, F-box E3 ubiquitin ligase in TCP14 proteolysis. 27208284 0 42 theme Class 71:75 arg1 Proteolysis 83:93 Class I TCP Proteolysis 71:93 Class I TCP Proteolysis to Promote Sensitivity to Cytokinin 71:129 The Putative O-Linked N-Acetylglucosamine Transferase SPINDLY Inhibits Class I TCP Proteolysis to Promote Sensitivity to Cytokinin. 27208284 9 43 theme CK-induced 1276:1285 arg1 pTCS 1306:1309 the CK-induced synthetic promoter pTCS 1272:1309 the CK-induced synthetic promoter pTCS 1272:1309 TCP15 overexpression enhanced the response of the CK-induced synthetic promoter pTCS to CK, suggesting that TCP14/15 affect early steps in CK signaling. 27208284 6 44 from mutation 863:870 arg1 CUL1 884:887 CUL1 884:887 CUL1 884:887 Mutation in the putative OGT domain of SPY (spy-3) stimulated TCP14 proteolysis by the 26S proteasome, which was reversed by mutation in CULLIN1 (CUL1), suggesting a role for SKP, CUL1, F-box E3 ubiquitin ligase in TCP14 proteolysis. 27208284 6 44 from mutation 863:870 arg1 CULLIN1 875:881 CULLIN1 875:881 CULLIN1 (CUL1) 875:888 Mutation in the putative OGT domain of SPY (spy-3) stimulated TCP14 proteolysis by the 26S proteasome, which was reversed by mutation in CULLIN1 (CUL1), suggesting a role for SKP, CUL1, F-box E3 ubiquitin ligase in TCP14 proteolysis. 27208284 4 45 dep identify 591:598 arg1 promote 657:663 promote 657:663 promote CK responses 657:676 Here, we aimed to identify how SPY regulates TCP14/15 activities and how these TCPs promote CK responses. 27208284 4 45 dep identify 591:598 arg1 regulates 608:616 regulates 608:616 regulates TCP14/15 activities 608:636 Here, we aimed to identify how SPY regulates TCP14/15 activities and how these TCPs promote CK responses. 27208284 2 46 theme cytokinin 338:346 arg1 responses 353:361 cytokinin (CK) responses 338:361 cytokinin (CK) responses 338:361 While SPY has been shown to suppress gibberellin signaling and to promote cytokinin (CK) responses, its catalytic OGT activity was never demonstrated and its effect on protein fate is not known. 27208284 2 47 theme protein 432:438 arg1 fate 440:443 protein fate 432:443 protein fate 432:443 While SPY has been shown to suppress gibberellin signaling and to promote cytokinin (CK) responses, its catalytic OGT activity was never demonstrated and its effect on protein fate is not known. 27208284 9 48 theme promoter 1297:1304 arg1 pTCS 1306:1309 the CK-induced synthetic promoter pTCS 1272:1309 the CK-induced synthetic promoter pTCS 1272:1309 TCP15 overexpression enhanced the response of the CK-induced synthetic promoter pTCS to CK, suggesting that TCP14/15 affect early steps in CK signaling. 27208284 10 49 theme TCP14/15 1429:1436 arg1 modification 1413:1424 posttranslational modification 1395:1424 posttranslational modification of TCP14/15 by SPY 1395:1443 We propose that posttranslational modification of TCP14/15 by SPY inhibits their proteolysis and that the accumulated proteins promote the activity of the CK phosphorelay cascade in developing Arabidopsis leaves and flowers. 27208284 3 50 theme CK 559:560 arg1 responses 562:570 CK responses 559:570 CK responses 559:570 We previously showed that SPY interacts physically and functionally with TCP14 and TCP15 to promote CK responses. 27208284 1 51 theme Arabidopsis 132:142 arg1 serine 195:200 serine 195:200 serine 195:200 Arabidopsis (Arabidopsis thaliana) SPINDLY (SPY) is a putative serine and threonine O-linked N-acetylglucosamine transferase (OGT). 27208284 1 51 theme Arabidopsis 132:142 arg1 SPY 176:178 SPY 176:178 SPY 176:178 Arabidopsis (Arabidopsis thaliana) SPINDLY (SPY) is a putative serine and threonine O-linked N-acetylglucosamine transferase (OGT). 27208284 1 51 theme Arabidopsis 132:142 arg1 SPINDLY 167:173 Arabidopsis (Arabidopsis thaliana) SPINDLY 132:173 Arabidopsis (Arabidopsis thaliana) SPINDLY (SPY) 132:179 Arabidopsis (Arabidopsis thaliana) SPINDLY (SPY) is a putative serine and threonine O-linked N-acetylglucosamine transferase (OGT). 27208284 8 52 theme increased 1087:1095 arg1 activity 1100:1107 The increased CK activity 1083:1107 The increased CK activity in TCP14/15-overexpressing flowers 1083:1142 The increased CK activity in TCP14/15-overexpressing flowers resulted from increased sensitivity to the hormone and not from higher CK levels. 27208284 1 53 theme O-linked 216:223 arg1 transferase 245:255 O-linked N-acetylglucosamine transferase 216:255 O-linked N-acetylglucosamine transferase (OGT) 216:261 Arabidopsis (Arabidopsis thaliana) SPINDLY (SPY) is a putative serine and threonine O-linked N-acetylglucosamine transferase (OGT). 27208284 1 53 theme O-linked 216:223 arg1 OGT 258:260 OGT 258:260 OGT 258:260 Arabidopsis (Arabidopsis thaliana) SPINDLY (SPY) is a putative serine and threonine O-linked N-acetylglucosamine transferase (OGT). 27208284 6 54 theme SPY 777:779 arg1 SPY 777:779 SPY 777:779 SPY (spy-3) 777:787 Mutation in the putative OGT domain of SPY (spy-3) stimulated TCP14 proteolysis by the 26S proteasome, which was reversed by mutation in CULLIN1 (CUL1), suggesting a role for SKP, CUL1, F-box E3 ubiquitin ligase in TCP14 proteolysis. 27208284 6 54 theme SPY 777:779 arg1 domain 767:772 the putative OGT domain 750:772 the putative OGT domain of SPY (spy-3) 750:787 Mutation in the putative OGT domain of SPY (spy-3) stimulated TCP14 proteolysis by the 26S proteasome, which was reversed by mutation in CULLIN1 (CUL1), suggesting a role for SKP, CUL1, F-box E3 ubiquitin ligase in TCP14 proteolysis. 27208284 1 55 theme Arabidopsis 145:155 arg1 Arabidopsis 132:142 Arabidopsis 132:142 Arabidopsis (Arabidopsis thaliana) SPINDLY (SPY) 132:179 Arabidopsis (Arabidopsis thaliana) SPINDLY (SPY) is a putative serine and threonine O-linked N-acetylglucosamine transferase (OGT). 27208284 1 55 theme Arabidopsis 145:155 arg1 thaliana 157:164 Arabidopsis thaliana 145:164 Arabidopsis thaliana 145:164 Arabidopsis (Arabidopsis thaliana) SPINDLY (SPY) is a putative serine and threonine O-linked N-acetylglucosamine transferase (OGT). 27208284 1 56 theme N-acetylglucosamine 225:243 arg1 transferase 245:255 O-linked N-acetylglucosamine transferase 216:255 O-linked N-acetylglucosamine transferase (OGT) 216:261 Arabidopsis (Arabidopsis thaliana) SPINDLY (SPY) is a putative serine and threonine O-linked N-acetylglucosamine transferase (OGT). 27208284 1 56 theme N-acetylglucosamine 225:243 arg1 OGT 258:260 OGT 258:260 OGT 258:260 Arabidopsis (Arabidopsis thaliana) SPINDLY (SPY) is a putative serine and threonine O-linked N-acetylglucosamine transferase (OGT). 27208284 0 57 theme TCP 79:81 arg1 Proteolysis 83:93 Class I TCP Proteolysis 71:93 Class I TCP Proteolysis to Promote Sensitivity to Cytokinin 71:129 The Putative O-Linked N-Acetylglucosamine Transferase SPINDLY Inhibits Class I TCP Proteolysis to Promote Sensitivity to Cytokinin. 27208284 6 58 from Mutation 738:745 arg1 SPY 777:779 SPY 777:779 SPY (spy-3) 777:787 Mutation in the putative OGT domain of SPY (spy-3) stimulated TCP14 proteolysis by the 26S proteasome, which was reversed by mutation in CULLIN1 (CUL1), suggesting a role for SKP, CUL1, F-box E3 ubiquitin ligase in TCP14 proteolysis. 27208284 6 58 from Mutation 738:745 arg1 domain 767:772 the putative OGT domain 750:772 the putative OGT domain of SPY (spy-3) 750:787 Mutation in the putative OGT domain of SPY (spy-3) stimulated TCP14 proteolysis by the 26S proteasome, which was reversed by mutation in CULLIN1 (CUL1), suggesting a role for SKP, CUL1, F-box E3 ubiquitin ligase in TCP14 proteolysis. 27208284 0 59 theme I 77:77 arg1 Proteolysis 83:93 Class I TCP Proteolysis 71:93 Class I TCP Proteolysis to Promote Sensitivity to Cytokinin 71:129 The Putative O-Linked N-Acetylglucosamine Transferase SPINDLY Inhibits Class I TCP Proteolysis to Promote Sensitivity to Cytokinin. 27208284 8 60 from activity 1100:1107 arg1 flowers 1136:1142 TCP14/15-overexpressing flowers 1112:1142 TCP14/15-overexpressing flowers 1112:1142 The increased CK activity in TCP14/15-overexpressing flowers resulted from increased sensitivity to the hormone and not from higher CK levels. 27208284 1 61 dep serine 195:200 arg1 transferase 245:255 O-linked N-acetylglucosamine transferase 216:255 O-linked N-acetylglucosamine transferase (OGT) 216:261 Arabidopsis (Arabidopsis thaliana) SPINDLY (SPY) is a putative serine and threonine O-linked N-acetylglucosamine transferase (OGT). 27208284 1 61 dep serine 195:200 arg1 OGT 258:260 OGT 258:260 OGT 258:260 Arabidopsis (Arabidopsis thaliana) SPINDLY (SPY) is a putative serine and threonine O-linked N-acetylglucosamine transferase (OGT). 27208284 9 62 from steps 1356:1360 arg1 signaling 1368:1376 CK signaling 1365:1376 CK signaling 1365:1376 TCP15 overexpression enhanced the response of the CK-induced synthetic promoter pTCS to CK, suggesting that TCP14/15 affect early steps in CK signaling. 27208284 7 63 theme CK 1069:1070 arg1 responses 1072:1080 the enhanced CK responses 1056:1080 the enhanced CK responses 1056:1080 TCP14 proteolysis in spy-3 suppressed all TCP14 misexpression phenotypes, including the enhanced CK responses. 27208284 9 64 theme synthetic 1287:1295 arg1 pTCS 1306:1309 the CK-induced synthetic promoter pTCS 1272:1309 the CK-induced synthetic promoter pTCS 1272:1309 TCP15 overexpression enhanced the response of the CK-induced synthetic promoter pTCS to CK, suggesting that TCP14/15 affect early steps in CK signaling. 26511985 7 0 theme glycome 1286:1292 arg1 analysis 1270:1277 a complete analysis 1259:1277 a complete analysis of the glycome in crude samples by any single technology 1259:1334 The study demonstrated the difficulty of carrying out a complete analysis of the glycome in crude samples by any single technology and the importance of rigorous optimization of the course of analysis from preprocessing to data interpretation. 26511985 6 1 from analysis 1128:1135 arg1 fractions 1152:1160 cell lysate fractions 1140:1160 cell lysate fractions prepared in a specified method by one lab 1140:1202 However, the reproducibility of the data was not improved dramatically in the subsequent analysis on cell lysate fractions prepared in a specified method by one lab. 26511985 1 2 theme Proteome 257:264 arg1 HUPO 280:283 HUPO 280:283 HUPO 280:283 The Human Disease Glycomics/Proteome Initiative (HGPI) is an activity in the Human Proteome Organization (HUPO) supported by leading researchers from international institutes and aims at development of disease-related glycomics/glycoproteomics analysis techniques. 26511985 1 2 theme Proteome 257:264 arg1 Organization 266:277 the Human Proteome Organization 247:277 the Human Proteome Organization (HUPO) supported by leading researchers from international institutes 247:347 The Human Disease Glycomics/Proteome Initiative (HGPI) is an activity in the Human Proteome Organization (HUPO) supported by leading researchers from international institutes and aims at development of disease-related glycomics/glycoproteomics analysis techniques. 26511985 7 3 from samples 1303:1309 arg1 analysis 1270:1277 a complete analysis 1259:1277 a complete analysis of the glycome in crude samples by any single technology 1259:1334 The study demonstrated the difficulty of carrying out a complete analysis of the glycome in crude samples by any single technology and the importance of rigorous optimization of the course of analysis from preprocessing to data interpretation. 26511985 8 4 contain carrying 1600:1607 arg1 requirements 1584:1595 the requirements 1580:1595 the requirements of carrying out the large-scale analysis of glycoproteins in complex cell samples 1580:1677 It suggests that another collaborative study employing the latest technologies in this rapidly evolving field will help to realize the requirements of carrying out the large-scale analysis of glycoproteins in complex cell samples. 26511985 8 4 contain carrying 1600:1607 arg2 analysis 1629:1636 the large-scale analysis 1613:1636 the large-scale analysis of glycoproteins 1613:1653 It suggests that another collaborative study employing the latest technologies in this rapidly evolving field will help to realize the requirements of carrying out the large-scale analysis of glycoproteins in complex cell samples. 26511985 1 5 theme Disease 184:190 arg1 HGPI 223:226 HGPI 223:226 HGPI 223:226 The Human Disease Glycomics/Proteome Initiative (HGPI) is an activity in the Human Proteome Organization (HUPO) supported by leading researchers from international institutes and aims at development of disease-related glycomics/glycoproteomics analysis techniques. 26511985 1 5 theme Disease 184:190 arg1 Initiative 211:220 The Human Disease Glycomics/Proteome Initiative 174:220 The Human Disease Glycomics/Proteome Initiative (HGPI) 174:227 The Human Disease Glycomics/Proteome Initiative (HGPI) is an activity in the Human Proteome Organization (HUPO) supported by leading researchers from international institutes and aims at development of disease-related glycomics/glycoproteomics analysis techniques. 26511985 1 5 theme Disease 184:190 arg1 activity 235:242 an activity 232:242 an activity in the Human Proteome Organization (HUPO) supported by leading researchers from international institutes 232:347 The Human Disease Glycomics/Proteome Initiative (HGPI) is an activity in the Human Proteome Organization (HUPO) supported by leading researchers from international institutes and aims at development of disease-related glycomics/glycoproteomics analysis techniques. 26511985 4 6 attach attached 800:807 arg1 proteins 812:819 proteins 812:819 proteins 812:819 This paper describes the third study, which was conducted to compare different approaches for quantitation of N- and O-linked glycans attached to proteins in crude biological samples. 26511985 4 6 attach attached 800:807 arg3 samples 841:847 crude biological samples 824:847 crude biological samples 824:847 This paper describes the third study, which was conducted to compare different approaches for quantitation of N- and O-linked glycans attached to proteins in crude biological samples. 26511985 4 6 attach attached 800:807 arg2 glycans 792:798 N- and O-linked glycans 776:798 N- and O-linked glycans attached to proteins in crude biological samples 776:847 This paper describes the third study, which was conducted to compare different approaches for quantitation of N- and O-linked glycans attached to proteins in crude biological samples. 26511985 3 7 theme appropriate 612:622 arg1 approach 635:642 the most appropriate analytical approach 603:642 the most appropriate analytical approach employed at the time 603:663 The first two were N- and O-glycan analyses of purified transferrin and immunoglobulin-G and assessed the most appropriate analytical approach employed at the time. 26511985 0 8 theme Human 103:107 arg1 study 167:171 HUPO Human Disease Glycomics/Proteome Initiative multi-institutional study 98:171 Comparison of analytical methods for profiling N- and O-linked glycans from cultured cell lines : HUPO Human Disease Glycomics/Proteome Initiative multi-institutional study. 0:172 Comparison of analytical methods for profiling N- and O-linked glycans from cultured cell lines : HUPO Human Disease Glycomics/Proteome Initiative multi-institutional study. 26511985 1 9 theme analysis 418:425 arg1 techniques 427:436 disease-related glycomics/glycoproteomics analysis techniques 376:436 disease-related glycomics/glycoproteomics analysis techniques 376:436 The Human Disease Glycomics/Proteome Initiative (HGPI) is an activity in the Human Proteome Organization (HUPO) supported by leading researchers from international institutes and aims at development of disease-related glycomics/glycoproteomics analysis techniques. 26511985 7 10 theme data 1428:1431 arg1 interpretation 1433:1446 data interpretation 1428:1446 data interpretation 1428:1446 The study demonstrated the difficulty of carrying out a complete analysis of the glycome in crude samples by any single technology and the importance of rigorous optimization of the course of analysis from preprocessing to data interpretation. 26511985 7 11 theme optimization 1367:1378 arg1 importance 1344:1353 the importance 1340:1353 the importance of rigorous optimization of the course of analysis from preprocessing to data interpretation 1340:1446 The study demonstrated the difficulty of carrying out a complete analysis of the glycome in crude samples by any single technology and the importance of rigorous optimization of the course of analysis from preprocessing to data interpretation. 26511985 7 11 theme optimization 1367:1378 arg1 difficulty 1232:1241 the difficulty 1228:1241 the difficulty of carrying out a complete analysis of the glycome in crude samples by any single technology 1228:1334 The study demonstrated the difficulty of carrying out a complete analysis of the glycome in crude samples by any single technology and the importance of rigorous optimization of the course of analysis from preprocessing to data interpretation. 26511985 4 12 theme third 691:695 arg1 study 697:701 the third study 687:701 the third study 687:701 This paper describes the third study, which was conducted to compare different approaches for quantitation of N- and O-linked glycans attached to proteins in crude biological samples. 26511985 0 13 theme Glycomics/Proteome 117:134 arg1 study 167:171 HUPO Human Disease Glycomics/Proteome Initiative multi-institutional study 98:171 Comparison of analytical methods for profiling N- and O-linked glycans from cultured cell lines : HUPO Human Disease Glycomics/Proteome Initiative multi-institutional study. 0:172 Comparison of analytical methods for profiling N- and O-linked glycans from cultured cell lines : HUPO Human Disease Glycomics/Proteome Initiative multi-institutional study. 26511985 0 14 theme multi-institutional 147:165 arg1 study 167:171 HUPO Human Disease Glycomics/Proteome Initiative multi-institutional study 98:171 Comparison of analytical methods for profiling N- and O-linked glycans from cultured cell lines : HUPO Human Disease Glycomics/Proteome Initiative multi-institutional study. 0:172 Comparison of analytical methods for profiling N- and O-linked glycans from cultured cell lines : HUPO Human Disease Glycomics/Proteome Initiative multi-institutional study. 26511985 7 15 from analysis 1270:1277 arg1 samples 1303:1309 crude samples 1297:1309 crude samples 1297:1309 The study demonstrated the difficulty of carrying out a complete analysis of the glycome in crude samples by any single technology and the importance of rigorous optimization of the course of analysis from preprocessing to data interpretation. 26511985 7 16 theme analysis 1397:1404 arg1 course 1387:1392 the course 1383:1392 the course of analysis from preprocessing to data interpretation 1383:1446 The study demonstrated the difficulty of carrying out a complete analysis of the glycome in crude samples by any single technology and the importance of rigorous optimization of the course of analysis from preprocessing to data interpretation. 26511985 1 17 from activity 235:242 arg1 HUPO 280:283 HUPO 280:283 HUPO 280:283 The Human Disease Glycomics/Proteome Initiative (HGPI) is an activity in the Human Proteome Organization (HUPO) supported by leading researchers from international institutes and aims at development of disease-related glycomics/glycoproteomics analysis techniques. 26511985 1 17 from activity 235:242 arg1 Organization 266:277 the Human Proteome Organization 247:277 the Human Proteome Organization (HUPO) supported by leading researchers from international institutes 247:347 The Human Disease Glycomics/Proteome Initiative (HGPI) is an activity in the Human Proteome Organization (HUPO) supported by leading researchers from international institutes and aims at development of disease-related glycomics/glycoproteomics analysis techniques. 26511985 5 18 theme variations 972:981 arg1 consequence 957:967 the consequence 953:967 the consequence of variations in the pre-processing sample preparation methodologies 953:1036 The preliminary analysis on cell pellets resulted in wildly varied glycan profiles, which was probably the consequence of variations in the pre-processing sample preparation methodologies. 26511985 5 18 theme variations 972:981 arg1 which 934:938 which 934:938 which 934:938 The preliminary analysis on cell pellets resulted in wildly varied glycan profiles, which was probably the consequence of variations in the pre-processing sample preparation methodologies. 26511985 8 19 theme evolving 1544:1551 arg1 field 1553:1557 this rapidly evolving field 1531:1557 this rapidly evolving field 1531:1557 It suggests that another collaborative study employing the latest technologies in this rapidly evolving field will help to realize the requirements of carrying out the large-scale analysis of glycoproteins in complex cell samples. 26511985 7 20 theme course 1387:1392 arg1 optimization 1367:1378 rigorous optimization 1358:1378 rigorous optimization of the course of analysis from preprocessing to data interpretation 1358:1446 The study demonstrated the difficulty of carrying out a complete analysis of the glycome in crude samples by any single technology and the importance of rigorous optimization of the course of analysis from preprocessing to data interpretation. 26511985 0 21 theme O-linked 54:61 arg1 glycans 63:69 O-linked glycans 54:69 O-linked glycans 54:69 Comparison of analytical methods for profiling N- and O-linked glycans from cultured cell lines : HUPO Human Disease Glycomics/Proteome Initiative multi-institutional study. 26511985 4 22 theme different 735:743 arg1 approaches 745:754 different approaches 735:754 different approaches for quantitation of N- and O-linked glycans attached to proteins in crude biological samples 735:847 This paper describes the third study, which was conducted to compare different approaches for quantitation of N- and O-linked glycans attached to proteins in crude biological samples. 26511985 0 23 theme cell 85:88 arg1 lines 90:94 cultured cell lines 76:94 cultured cell lines 76:94 Comparison of analytical methods for profiling N- and O-linked glycans from cultured cell lines : HUPO Human Disease Glycomics/Proteome Initiative multi-institutional study. 26511985 5 24 from analysis 866:873 arg1 pellets 883:889 cell pellets 878:889 cell pellets 878:889 The preliminary analysis on cell pellets resulted in wildly varied glycan profiles, which was probably the consequence of variations in the pre-processing sample preparation methodologies. 26511985 7 25 from course 1387:1392 arg1 preprocessing 1411:1423 preprocessing 1411:1423 preprocessing 1411:1423 The study demonstrated the difficulty of carrying out a complete analysis of the glycome in crude samples by any single technology and the importance of rigorous optimization of the course of analysis from preprocessing to data interpretation. 26511985 1 26 theme disease-related 376:390 arg1 techniques 427:436 disease-related glycomics/glycoproteomics analysis techniques 376:436 disease-related glycomics/glycoproteomics analysis techniques 376:436 The Human Disease Glycomics/Proteome Initiative (HGPI) is an activity in the Human Proteome Organization (HUPO) supported by leading researchers from international institutes and aims at development of disease-related glycomics/glycoproteomics analysis techniques. 26511985 2 27 theme pilot 486:490 arg1 studies 492:498 three pilot studies 480:498 three pilot studies 480:498 Since 2004, the initiative has conducted three pilot studies. 26511985 5 28 theme preliminary 854:864 arg1 analysis 866:873 The preliminary analysis 850:873 The preliminary analysis on cell pellets 850:889 The preliminary analysis on cell pellets resulted in wildly varied glycan profiles, which was probably the consequence of variations in the pre-processing sample preparation methodologies. 26511985 8 29 gly glycoproteins 1641:1653 arg1 glycoproteins 1641:1653 glycoproteins 1641:1653 glycoproteins 1641:1653 It suggests that another collaborative study employing the latest technologies in this rapidly evolving field will help to realize the requirements of carrying out the large-scale analysis of glycoproteins in complex cell samples. 26511985 7 30 from preprocessing 1411:1423 arg1 analysis 1397:1404 analysis 1397:1404 analysis from preprocessing to data interpretation 1397:1446 The study demonstrated the difficulty of carrying out a complete analysis of the glycome in crude samples by any single technology and the importance of rigorous optimization of the course of analysis from preprocessing to data interpretation. 26511985 7 30 from preprocessing 1411:1423 arg1 course 1387:1392 the course 1383:1392 the course of analysis from preprocessing to data interpretation 1383:1446 The study demonstrated the difficulty of carrying out a complete analysis of the glycome in crude samples by any single technology and the importance of rigorous optimization of the course of analysis from preprocessing to data interpretation. 26511985 6 31 theme subsequent 1117:1126 arg1 analysis 1128:1135 the subsequent analysis 1113:1135 the subsequent analysis on cell lysate fractions prepared in a specified method by one lab 1113:1202 However, the reproducibility of the data was not improved dramatically in the subsequent analysis on cell lysate fractions prepared in a specified method by one lab. 26511985 4 32 theme glycans 792:798 arg1 quantitation 760:771 quantitation 760:771 quantitation of N- and O-linked glycans attached to proteins in crude biological samples 760:847 This paper describes the third study, which was conducted to compare different approaches for quantitation of N- and O-linked glycans attached to proteins in crude biological samples. 26511985 0 33 theme analytical 14:23 arg1 methods 25:31 analytical methods 14:31 analytical methods for profiling N- and O-linked glycans from cultured cell lines 14:94 Comparison of analytical methods for profiling N- and O-linked glycans from cultured cell lines : HUPO Human Disease Glycomics/Proteome Initiative multi-institutional study. 26511985 5 34 theme sample 1005:1010 arg1 preparation 1012:1022 the pre-processing sample preparation 986:1022 the pre-processing sample preparation methodologies 986:1036 The preliminary analysis on cell pellets resulted in wildly varied glycan profiles, which was probably the consequence of variations in the pre-processing sample preparation methodologies. 26511985 8 35 theme large-scale 1617:1627 arg1 analysis 1629:1636 the large-scale analysis 1613:1636 the large-scale analysis of glycoproteins 1613:1653 It suggests that another collaborative study employing the latest technologies in this rapidly evolving field will help to realize the requirements of carrying out the large-scale analysis of glycoproteins in complex cell samples. 26511985 5 36 theme wildly 903:908 arg1 profiles 924:931 wildly varied glycan profiles 903:931 wildly varied glycan profiles 903:931 The preliminary analysis on cell pellets resulted in wildly varied glycan profiles, which was probably the consequence of variations in the pre-processing sample preparation methodologies. 26511985 1 37 theme leading 299:305 arg1 researchers 307:317 leading researchers 299:317 leading researchers from international institutes 299:347 The Human Disease Glycomics/Proteome Initiative (HGPI) is an activity in the Human Proteome Organization (HUPO) supported by leading researchers from international institutes and aims at development of disease-related glycomics/glycoproteomics analysis techniques. 26511985 3 38 theme N- 520:521 arg1 analyses 536:543 N- and O-glycan analyses 520:543 N- and O-glycan analyses of purified transferrin and immunoglobulin-G 520:588 The first two were N- and O-glycan analyses of purified transferrin and immunoglobulin-G and assessed the most appropriate analytical approach employed at the time. 26511985 3 38 theme N- 520:521 arg1 two 511:513 two 511:513 two 511:513 The first two were N- and O-glycan analyses of purified transferrin and immunoglobulin-G and assessed the most appropriate analytical approach employed at the time. 26511985 8 39 theme collaborative 1474:1486 arg1 study 1488:1492 another collaborative study 1466:1492 another collaborative study employing the latest technologies in this rapidly evolving field 1466:1557 It suggests that another collaborative study employing the latest technologies in this rapidly evolving field will help to realize the requirements of carrying out the large-scale analysis of glycoproteins in complex cell samples. 26511985 8 40 theme cell 1666:1669 arg1 samples 1671:1677 complex cell samples 1658:1677 complex cell samples 1658:1677 It suggests that another collaborative study employing the latest technologies in this rapidly evolving field will help to realize the requirements of carrying out the large-scale analysis of glycoproteins in complex cell samples. 26511985 5 41 theme varied 910:915 arg1 profiles 924:931 wildly varied glycan profiles 903:931 wildly varied glycan profiles 903:931 The preliminary analysis on cell pellets resulted in wildly varied glycan profiles, which was probably the consequence of variations in the pre-processing sample preparation methodologies. 26511985 0 42 dep Comparison 0:9 arg1 study 167:171 HUPO Human Disease Glycomics/Proteome Initiative multi-institutional study 98:171 Comparison of analytical methods for profiling N- and O-linked glycans from cultured cell lines : HUPO Human Disease Glycomics/Proteome Initiative multi-institutional study. 0:172 Comparison of analytical methods for profiling N- and O-linked glycans from cultured cell lines : HUPO Human Disease Glycomics/Proteome Initiative multi-institutional study. 26511985 4 43 link O-linked 783:790 arg1 glycans 792:798 N- and O-linked glycans 776:798 N- and O-linked glycans attached to proteins in crude biological samples 776:847 This paper describes the third study, which was conducted to compare different approaches for quantitation of N- and O-linked glycans attached to proteins in crude biological samples. 26511985 7 44 theme complete 1261:1268 arg1 analysis 1270:1277 a complete analysis 1259:1277 a complete analysis of the glycome in crude samples by any single technology 1259:1334 The study demonstrated the difficulty of carrying out a complete analysis of the glycome in crude samples by any single technology and the importance of rigorous optimization of the course of analysis from preprocessing to data interpretation. 26511985 3 45 theme O-glycan 527:534 arg1 analyses 536:543 N- and O-glycan analyses 520:543 N- and O-glycan analyses of purified transferrin and immunoglobulin-G 520:588 The first two were N- and O-glycan analyses of purified transferrin and immunoglobulin-G and assessed the most appropriate analytical approach employed at the time. 26511985 3 45 theme O-glycan 527:534 arg1 two 511:513 two 511:513 two 511:513 The first two were N- and O-glycan analyses of purified transferrin and immunoglobulin-G and assessed the most appropriate analytical approach employed at the time. 26511985 1 46 theme Human 251:255 arg1 HUPO 280:283 HUPO 280:283 HUPO 280:283 The Human Disease Glycomics/Proteome Initiative (HGPI) is an activity in the Human Proteome Organization (HUPO) supported by leading researchers from international institutes and aims at development of disease-related glycomics/glycoproteomics analysis techniques. 26511985 1 46 theme Human 251:255 arg1 Organization 266:277 the Human Proteome Organization 247:277 the Human Proteome Organization (HUPO) supported by leading researchers from international institutes 247:347 The Human Disease Glycomics/Proteome Initiative (HGPI) is an activity in the Human Proteome Organization (HUPO) supported by leading researchers from international institutes and aims at development of disease-related glycomics/glycoproteomics analysis techniques. 26511985 7 47 from glycome 1286:1292 arg1 samples 1303:1309 crude samples 1297:1309 crude samples 1297:1309 The study demonstrated the difficulty of carrying out a complete analysis of the glycome in crude samples by any single technology and the importance of rigorous optimization of the course of analysis from preprocessing to data interpretation. 26511985 6 48 theme lysate 1145:1150 arg1 fractions 1152:1160 cell lysate fractions 1140:1160 cell lysate fractions prepared in a specified method by one lab 1140:1202 However, the reproducibility of the data was not improved dramatically in the subsequent analysis on cell lysate fractions prepared in a specified method by one lab. 26511985 3 49 theme immunoglobulin-G 573:588 arg1 analyses 536:543 N- and O-glycan analyses 520:543 N- and O-glycan analyses of purified transferrin and immunoglobulin-G 520:588 The first two were N- and O-glycan analyses of purified transferrin and immunoglobulin-G and assessed the most appropriate analytical approach employed at the time. 26511985 3 49 theme immunoglobulin-G 573:588 arg1 two 511:513 two 511:513 two 511:513 The first two were N- and O-glycan analyses of purified transferrin and immunoglobulin-G and assessed the most appropriate analytical approach employed at the time. 26511985 5 50 from methodologies 1024:1036 arg1 consequence 957:967 the consequence 953:967 the consequence of variations in the pre-processing sample preparation methodologies 953:1036 The preliminary analysis on cell pellets resulted in wildly varied glycan profiles, which was probably the consequence of variations in the pre-processing sample preparation methodologies. 26511985 5 50 from methodologies 1024:1036 arg1 which 934:938 which 934:938 which 934:938 The preliminary analysis on cell pellets resulted in wildly varied glycan profiles, which was probably the consequence of variations in the pre-processing sample preparation methodologies. 26511985 3 51 theme transferrin 557:567 arg1 analyses 536:543 N- and O-glycan analyses 520:543 N- and O-glycan analyses of purified transferrin and immunoglobulin-G 520:588 The first two were N- and O-glycan analyses of purified transferrin and immunoglobulin-G and assessed the most appropriate analytical approach employed at the time. 26511985 3 51 theme transferrin 557:567 arg1 two 511:513 two 511:513 two 511:513 The first two were N- and O-glycan analyses of purified transferrin and immunoglobulin-G and assessed the most appropriate analytical approach employed at the time. 26511985 1 52 theme Glycomics/Proteome 192:209 arg1 HGPI 223:226 HGPI 223:226 HGPI 223:226 The Human Disease Glycomics/Proteome Initiative (HGPI) is an activity in the Human Proteome Organization (HUPO) supported by leading researchers from international institutes and aims at development of disease-related glycomics/glycoproteomics analysis techniques. 26511985 1 52 theme Glycomics/Proteome 192:209 arg1 Initiative 211:220 The Human Disease Glycomics/Proteome Initiative 174:220 The Human Disease Glycomics/Proteome Initiative (HGPI) 174:227 The Human Disease Glycomics/Proteome Initiative (HGPI) is an activity in the Human Proteome Organization (HUPO) supported by leading researchers from international institutes and aims at development of disease-related glycomics/glycoproteomics analysis techniques. 26511985 1 52 theme Glycomics/Proteome 192:209 arg1 activity 235:242 an activity 232:242 an activity in the Human Proteome Organization (HUPO) supported by leading researchers from international institutes 232:347 The Human Disease Glycomics/Proteome Initiative (HGPI) is an activity in the Human Proteome Organization (HUPO) supported by leading researchers from international institutes and aims at development of disease-related glycomics/glycoproteomics analysis techniques. 26511985 1 53 theme Human 178:182 arg1 HGPI 223:226 HGPI 223:226 HGPI 223:226 The Human Disease Glycomics/Proteome Initiative (HGPI) is an activity in the Human Proteome Organization (HUPO) supported by leading researchers from international institutes and aims at development of disease-related glycomics/glycoproteomics analysis techniques. 26511985 1 53 theme Human 178:182 arg1 Initiative 211:220 The Human Disease Glycomics/Proteome Initiative 174:220 The Human Disease Glycomics/Proteome Initiative (HGPI) 174:227 The Human Disease Glycomics/Proteome Initiative (HGPI) is an activity in the Human Proteome Organization (HUPO) supported by leading researchers from international institutes and aims at development of disease-related glycomics/glycoproteomics analysis techniques. 26511985 1 53 theme Human 178:182 arg1 activity 235:242 an activity 232:242 an activity in the Human Proteome Organization (HUPO) supported by leading researchers from international institutes 232:347 The Human Disease Glycomics/Proteome Initiative (HGPI) is an activity in the Human Proteome Organization (HUPO) supported by leading researchers from international institutes and aims at development of disease-related glycomics/glycoproteomics analysis techniques. 26511985 5 54 theme glycan 917:922 arg1 profiles 924:931 wildly varied glycan profiles 903:931 wildly varied glycan profiles 903:931 The preliminary analysis on cell pellets resulted in wildly varied glycan profiles, which was probably the consequence of variations in the pre-processing sample preparation methodologies. 26511985 0 55 theme Disease 109:115 arg1 study 167:171 HUPO Human Disease Glycomics/Proteome Initiative multi-institutional study 98:171 Comparison of analytical methods for profiling N- and O-linked glycans from cultured cell lines : HUPO Human Disease Glycomics/Proteome Initiative multi-institutional study. 0:172 Comparison of analytical methods for profiling N- and O-linked glycans from cultured cell lines : HUPO Human Disease Glycomics/Proteome Initiative multi-institutional study. 26511985 5 56 theme cell 878:881 arg1 pellets 883:889 cell pellets 878:889 cell pellets 878:889 The preliminary analysis on cell pellets resulted in wildly varied glycan profiles, which was probably the consequence of variations in the pre-processing sample preparation methodologies. 26511985 8 57 theme latest 1508:1513 arg1 technologies 1515:1526 the latest technologies 1504:1526 the latest technologies 1504:1526 It suggests that another collaborative study employing the latest technologies in this rapidly evolving field will help to realize the requirements of carrying out the large-scale analysis of glycoproteins in complex cell samples. 26511985 0 58 theme Initiative 136:145 arg1 study 167:171 HUPO Human Disease Glycomics/Proteome Initiative multi-institutional study 98:171 Comparison of analytical methods for profiling N- and O-linked glycans from cultured cell lines : HUPO Human Disease Glycomics/Proteome Initiative multi-institutional study. 0:172 Comparison of analytical methods for profiling N- and O-linked glycans from cultured cell lines : HUPO Human Disease Glycomics/Proteome Initiative multi-institutional study. 26511985 1 59 theme techniques 427:436 arg1 development 361:371 development 361:371 development of disease-related glycomics/glycoproteomics analysis techniques 361:436 The Human Disease Glycomics/Proteome Initiative (HGPI) is an activity in the Human Proteome Organization (HUPO) supported by leading researchers from international institutes and aims at development of disease-related glycomics/glycoproteomics analysis techniques. 26511985 3 60 theme analytical 624:633 arg1 approach 635:642 the most appropriate analytical approach 603:642 the most appropriate analytical approach employed at the time 603:663 The first two were N- and O-glycan analyses of purified transferrin and immunoglobulin-G and assessed the most appropriate analytical approach employed at the time. 26511985 4 61 theme biological 830:839 arg1 samples 841:847 crude biological samples 824:847 crude biological samples 824:847 This paper describes the third study, which was conducted to compare different approaches for quantitation of N- and O-linked glycans attached to proteins in crude biological samples. 26511985 0 62 from lines 90:94 arg1 N- 47:48 N- 47:48 N- 47:48 Comparison of analytical methods for profiling N- and O-linked glycans from cultured cell lines : HUPO Human Disease Glycomics/Proteome Initiative multi-institutional study. 26511985 0 62 from lines 90:94 arg1 glycans 63:69 O-linked glycans 54:69 O-linked glycans 54:69 Comparison of analytical methods for profiling N- and O-linked glycans from cultured cell lines : HUPO Human Disease Glycomics/Proteome Initiative multi-institutional study. 26511985 6 63 theme data 1075:1078 arg1 reproducibility 1052:1066 the reproducibility 1048:1066 the reproducibility of the data 1048:1078 However, the reproducibility of the data was not improved dramatically in the subsequent analysis on cell lysate fractions prepared in a specified method by one lab. 26511985 0 64 theme cultured 76:83 arg1 lines 90:94 cultured cell lines 76:94 cultured cell lines 76:94 Comparison of analytical methods for profiling N- and O-linked glycans from cultured cell lines : HUPO Human Disease Glycomics/Proteome Initiative multi-institutional study. 26511985 5 65 theme preparation 1012:1022 arg1 methodologies 1024:1036 the pre-processing sample preparation methodologies 986:1036 the pre-processing sample preparation methodologies 986:1036 The preliminary analysis on cell pellets resulted in wildly varied glycan profiles, which was probably the consequence of variations in the pre-processing sample preparation methodologies. 26511985 0 66 theme HUPO 98:101 arg1 study 167:171 HUPO Human Disease Glycomics/Proteome Initiative multi-institutional study 98:171 Comparison of analytical methods for profiling N- and O-linked glycans from cultured cell lines : HUPO Human Disease Glycomics/Proteome Initiative multi-institutional study. 0:172 Comparison of analytical methods for profiling N- and O-linked glycans from cultured cell lines : HUPO Human Disease Glycomics/Proteome Initiative multi-institutional study. 26511985 6 67 theme cell 1140:1143 arg1 fractions 1152:1160 cell lysate fractions 1140:1160 cell lysate fractions prepared in a specified method by one lab 1140:1202 However, the reproducibility of the data was not improved dramatically in the subsequent analysis on cell lysate fractions prepared in a specified method by one lab. 26511985 1 68 theme glycomics/glycoproteomics 392:416 arg1 techniques 427:436 disease-related glycomics/glycoproteomics analysis techniques 376:436 disease-related glycomics/glycoproteomics analysis techniques 376:436 The Human Disease Glycomics/Proteome Initiative (HGPI) is an activity in the Human Proteome Organization (HUPO) supported by leading researchers from international institutes and aims at development of disease-related glycomics/glycoproteomics analysis techniques. 26511985 5 69 from variations 972:981 arg1 methodologies 1024:1036 the pre-processing sample preparation methodologies 986:1036 the pre-processing sample preparation methodologies 986:1036 The preliminary analysis on cell pellets resulted in wildly varied glycan profiles, which was probably the consequence of variations in the pre-processing sample preparation methodologies. 26511985 7 70 theme rigorous 1358:1365 arg1 optimization 1367:1378 rigorous optimization 1358:1378 rigorous optimization of the course of analysis from preprocessing to data interpretation 1358:1446 The study demonstrated the difficulty of carrying out a complete analysis of the glycome in crude samples by any single technology and the importance of rigorous optimization of the course of analysis from preprocessing to data interpretation. 26511985 4 71 theme N- 776:777 arg1 glycans 792:798 N- and O-linked glycans 776:798 N- and O-linked glycans attached to proteins in crude biological samples 776:847 This paper describes the third study, which was conducted to compare different approaches for quantitation of N- and O-linked glycans attached to proteins in crude biological samples. 26511985 0 72 theme methods 25:31 arg1 Comparison 0:9 Comparison 0:9 Comparison of analytical methods for profiling N- and O-linked glycans from cultured cell lines : HUPO Human Disease Glycomics/Proteome Initiative multi-institutional study. 0:172 Comparison of analytical methods for profiling N- and O-linked glycans from cultured cell lines : HUPO Human Disease Glycomics/Proteome Initiative multi-institutional study. 26511985 5 73 from consequence 957:967 arg1 methodologies 1024:1036 the pre-processing sample preparation methodologies 986:1036 the pre-processing sample preparation methodologies 986:1036 The preliminary analysis on cell pellets resulted in wildly varied glycan profiles, which was probably the consequence of variations in the pre-processing sample preparation methodologies. 26511985 5 74 theme pre-processing 990:1003 arg1 preparation 1012:1022 the pre-processing sample preparation 986:1022 the pre-processing sample preparation methodologies 986:1036 The preliminary analysis on cell pellets resulted in wildly varied glycan profiles, which was probably the consequence of variations in the pre-processing sample preparation methodologies. 26511985 4 75 theme O-linked 783:790 arg1 glycans 792:798 N- and O-linked glycans 776:798 N- and O-linked glycans attached to proteins in crude biological samples 776:847 This paper describes the third study, which was conducted to compare different approaches for quantitation of N- and O-linked glycans attached to proteins in crude biological samples. 26511985 8 76 theme glycoproteins 1641:1653 arg1 analysis 1629:1636 the large-scale analysis 1613:1636 the large-scale analysis of glycoproteins 1613:1653 It suggests that another collaborative study employing the latest technologies in this rapidly evolving field will help to realize the requirements of carrying out the large-scale analysis of glycoproteins in complex cell samples. 26511985 7 77 contain carrying 1246:1253 arg2 analysis 1270:1277 a complete analysis 1259:1277 a complete analysis of the glycome in crude samples by any single technology 1259:1334 The study demonstrated the difficulty of carrying out a complete analysis of the glycome in crude samples by any single technology and the importance of rigorous optimization of the course of analysis from preprocessing to data interpretation. 26511985 7 77 contain carrying 1246:1253 arg1 difficulty 1232:1241 the difficulty 1228:1241 the difficulty of carrying out a complete analysis of the glycome in crude samples by any single technology 1228:1334 The study demonstrated the difficulty of carrying out a complete analysis of the glycome in crude samples by any single technology and the importance of rigorous optimization of the course of analysis from preprocessing to data interpretation. 26511985 1 78 from institutes 338:347 arg1 researchers 307:317 leading researchers 299:317 leading researchers from international institutes 299:347 The Human Disease Glycomics/Proteome Initiative (HGPI) is an activity in the Human Proteome Organization (HUPO) supported by leading researchers from international institutes and aims at development of disease-related glycomics/glycoproteomics analysis techniques. 26511985 7 79 theme single 1318:1323 arg1 technology 1325:1334 any single technology 1314:1334 any single technology 1314:1334 The study demonstrated the difficulty of carrying out a complete analysis of the glycome in crude samples by any single technology and the importance of rigorous optimization of the course of analysis from preprocessing to data interpretation. 26511985 8 80 theme complex 1658:1664 arg1 samples 1671:1677 complex cell samples 1658:1677 complex cell samples 1658:1677 It suggests that another collaborative study employing the latest technologies in this rapidly evolving field will help to realize the requirements of carrying out the large-scale analysis of glycoproteins in complex cell samples. 26511985 1 81 theme international 324:336 arg1 institutes 338:347 international institutes 324:347 international institutes 324:347 The Human Disease Glycomics/Proteome Initiative (HGPI) is an activity in the Human Proteome Organization (HUPO) supported by leading researchers from international institutes and aims at development of disease-related glycomics/glycoproteomics analysis techniques. 26511985 0 82 link O-linked 54:61 arg1 glycans 63:69 O-linked glycans 54:69 O-linked glycans 54:69 Comparison of analytical methods for profiling N- and O-linked glycans from cultured cell lines : HUPO Human Disease Glycomics/Proteome Initiative multi-institutional study. 26511985 6 83 theme specified 1176:1184 arg1 method 1186:1191 a specified method 1174:1191 a specified method 1174:1191 However, the reproducibility of the data was not improved dramatically in the subsequent analysis on cell lysate fractions prepared in a specified method by one lab. 26511985 4 84 theme crude 824:828 arg1 samples 841:847 crude biological samples 824:847 crude biological samples 824:847 This paper describes the third study, which was conducted to compare different approaches for quantitation of N- and O-linked glycans attached to proteins in crude biological samples. 26511985 7 85 theme crude 1297:1301 arg1 samples 1303:1309 crude samples 1297:1309 crude samples 1297:1309 The study demonstrated the difficulty of carrying out a complete analysis of the glycome in crude samples by any single technology and the importance of rigorous optimization of the course of analysis from preprocessing to data interpretation. 26511985 3 86 theme purified 548:555 arg1 transferrin 557:567 transferrin 557:567 transferrin 557:567 The first two were N- and O-glycan analyses of purified transferrin and immunoglobulin-G and assessed the most appropriate analytical approach employed at the time. 24713123 2 0 from COCs 419:422 arg1 O-GlcNAcylated 395:408 O-GlcNAcylated 395:408 O-GlcNAcylated 395:408 SUMMARY ANSWER Heat shock protein 90 (HSP90) was identified and confirmed as being O-GlcNAcylated in mouse COCs under hyperglycaemic conditions (modelled using glucosamine), causing detrimental outcomes for embryo development. 24713123 3 1 theme matrix 708:713 arg1 production 715:724 cumulus matrix production 700:724 cumulus matrix production during COC maturation 700:746 WHAT IS KNOWN ALREADY O-GlcNAcylation of proteins occurs as a result of increased activity of the hexosamine biosynthesis pathway, which provides substrates for cumulus matrix production during COC maturation, and also for O-GlcNAcylation. 24713123 5 2 from targets 1199:1205 arg1 maturation 1255:1264 oocyte maturation 1248:1264 oocyte maturation 1248:1264 STUDY DESIGN, SIZE, DURATION This study was designed to examine the effect of hyperglycaemic conditions (using the hyperglycaemic mimetic, glucosamine) on O-GlcNAc levels in the mouse COC, and furthermore to identify potential candidate proteins which are targets of this modification, and their roles in oocyte maturation. 24713123 8 3 theme western 1727:1733 arg1 blotting 1735:1742 western blotting 1727:1742 western blotting 1727:1742 For glycosylated HSP90 levels, and to test OGT-HSP90 interaction, immunoprecipitation was performed prior to western blotting. 24713123 7 4 theme responsible 1490:1500 arg1 OGT 1474:1476 OGT 1474:1476 OGT 1474:1476 Levels of O-GlcNAcylated proteins, HSP90 and O-GlcNAc transferase (OGT, the enzyme responsible for O-GlcNAcylation) in COCs were measured using western blot, and localization observed using immunocytochemistry. 24713123 7 4 theme responsible 1490:1500 arg1 enzyme 1483:1488 the enzyme 1479:1488 the enzyme responsible for O-GlcNAcylation 1479:1520 Levels of O-GlcNAcylated proteins, HSP90 and O-GlcNAc transferase (OGT, the enzyme responsible for O-GlcNAcylation) in COCs were measured using western blot, and localization observed using immunocytochemistry. 24713123 4 5 theme O-GlcNAcylation 926:940 arg1 mechanism 903:911 the mechanism 899:911 the mechanism of increased O-GlcNAcylation 899:940 COCs matured under hyperglycaemic conditions have decreased developmental competence, mediated at least in part through the mechanism of increased O-GlcNAcylation. 24713123 7 6 theme O-GlcNAc 1452:1459 arg1 proteins 1432:1439 O-GlcNAcylated proteins 1417:1439 O-GlcNAcylated proteins 1417:1439 Levels of O-GlcNAcylated proteins, HSP90 and O-GlcNAc transferase (OGT, the enzyme responsible for O-GlcNAcylation) in COCs were measured using western blot, and localization observed using immunocytochemistry. 24713123 7 6 theme O-GlcNAc 1452:1459 arg1 transferase 1461:1471 O-GlcNAc transferase 1452:1471 O-GlcNAc transferase (OGT, the enzyme responsible for O-GlcNAcylation) 1452:1521 Levels of O-GlcNAcylated proteins, HSP90 and O-GlcNAc transferase (OGT, the enzyme responsible for O-GlcNAcylation) in COCs were measured using western blot, and localization observed using immunocytochemistry. 24713123 8 7 theme OGT-HSP90 1661:1669 arg1 interaction 1671:1681 OGT-HSP90 interaction 1661:1681 OGT-HSP90 interaction 1661:1681 For glycosylated HSP90 levels, and to test OGT-HSP90 interaction, immunoprecipitation was performed prior to western blotting. 24713123 17 8 theme STUDY 3106:3110 arg1 S 3139:3139 STUDY FUNDING/COMPETING INTEREST(S) 3106:3140 STUDY FUNDING/COMPETING INTEREST(S) This work was supported by a programme grant from the National Health and Medical Research Council, Australia, ID 453556. 3106:3262 STUDY FUNDING/COMPETING INTEREST(S) This work was supported by a programme grant from the National Health and Medical Research Council, Australia, ID 453556. 24713123 16 9 theme oocyte 3090:3095 arg1 quality 3097:3103 oocyte quality 3090:3103 oocyte quality 3090:3103 WIDER IMPLICATIONS OF THE FINDINGS This study leads to a new understanding of how diabetes influences oocyte competence and provides insight into possible therapeutic interventions based on inhibiting HSP90 to improve oocyte quality. 24713123 10 10 theme protein 1994:2000 arg1 levels 2002:2007 detectable O-GlcNAcylated protein levels 1968:2007 detectable O-GlcNAcylated protein levels 1968:2007 MAIN RESULTS AND THE ROLE OF CHANCE Addition of the hyperglycaemic mimetic glucosamine to IVM medium for mouse COCs increased detectable O-GlcNAcylated protein levels (by western blot and immunocytochemistry), and this effect was reversed using an OGT inhibitor (P < 0.05). 24713123 13 11 theme treatment 2520:2528 arg1 time 2530:2533 treatment time 2520:2533 treatment time 2520:2533 LIMITATIONS, REASONS FOR CAUTION In vitro maturation of COCs was used so that treatment time could be limited to the 17 h of maturation prior to ovulation. 24713123 1 12 theme beta-O-linked 176:188 arg1 glycosylation 190:202 beta-O-linked glycosylation 176:202 beta-O-linked glycosylation (O-GlcNAcylation) 176:220 STUDY QUESTION What is the effect of beta-O-linked glycosylation (O-GlcNAcylation) on specific proteins in the cumulus-oocyte complex (COC) under hyperglycaemic conditions? 24713123 1 12 theme beta-O-linked 176:188 arg1 O-GlcNAcylation 205:219 O-GlcNAcylation 205:219 O-GlcNAcylation 205:219 STUDY QUESTION What is the effect of beta-O-linked glycosylation (O-GlcNAcylation) on specific proteins in the cumulus-oocyte complex (COC) under hyperglycaemic conditions? 24713123 7 13 theme proteins 1432:1439 arg1 Levels 1407:1412 Levels 1407:1412 Levels of O-GlcNAcylated proteins, HSP90 and O-GlcNAc transferase (OGT, the enzyme responsible for O-GlcNAcylation) in COCs 1407:1529 Levels of O-GlcNAcylated proteins, HSP90 and O-GlcNAc transferase (OGT, the enzyme responsible for O-GlcNAcylation) in COCs were measured using western blot, and localization observed using immunocytochemistry. 24713123 17 14 theme Research 3224:3231 arg1 Council 3233:3239 Medical Research Council 3216:3239 Medical Research Council 3216:3239 STUDY FUNDING/COMPETING INTEREST(S) This work was supported by a programme grant from the National Health and Medical Research Council, Australia, ID 453556. 24713123 17 15 from Council 3233:3239 arg1 Australia 3242:3250 Australia 3242:3250 Australia 3242:3250 STUDY FUNDING/COMPETING INTEREST(S) This work was supported by a programme grant from the National Health and Medical Research Council, Australia, ID 453556. 24713123 17 15 from Council 3233:3239 arg1 453556 3256:3261 ID 453556 3253:3261 ID 453556 3253:3261 STUDY FUNDING/COMPETING INTEREST(S) This work was supported by a programme grant from the National Health and Medical Research Council, Australia, ID 453556. 24713123 17 15 from Council 3233:3239 arg1 grant 3181:3185 a programme grant 3169:3185 a programme grant from the National Health and Medical Research Council 3169:3239 STUDY FUNDING/COMPETING INTEREST(S) This work was supported by a programme grant from the National Health and Medical Research Council, Australia, ID 453556. 24713123 2 16 theme Heat 327:330 arg1 protein 338:344 SUMMARY ANSWER Heat shock protein 90 312:347 SUMMARY ANSWER Heat shock protein 90 (HSP90) 312:355 SUMMARY ANSWER Heat shock protein 90 (HSP90) was identified and confirmed as being O-GlcNAcylated in mouse COCs under hyperglycaemic conditions (modelled using glucosamine), causing detrimental outcomes for embryo development. 24713123 2 16 theme Heat 327:330 arg1 HSP90 350:354 HSP90 350:354 HSP90 350:354 SUMMARY ANSWER Heat shock protein 90 (HSP90) was identified and confirmed as being O-GlcNAcylated in mouse COCs under hyperglycaemic conditions (modelled using glucosamine), causing detrimental outcomes for embryo development. 24713123 6 17 theme 21-day-old 1318:1327 arg1 CBA 1343:1345 21-day-old superovulated CBA × 1318:1347 21-day-old superovulated CBA × C57BL6 F1 hybrid female mice 1318:1376 PARTICIPANTS/MATERIALS, SETTING, METHODS COCs from 21-day-old superovulated CBA × C57BL6 F1 hybrid female mice were matured in vitro (IVM). 24713123 5 18 mod modification 1215:1226 arg1 oocyte 1248:1253 oocyte maturation 1248:1264 oocyte maturation 1248:1264 STUDY DESIGN, SIZE, DURATION This study was designed to examine the effect of hyperglycaemic conditions (using the hyperglycaemic mimetic, glucosamine) on O-GlcNAc levels in the mouse COC, and furthermore to identify potential candidate proteins which are targets of this modification, and their roles in oocyte maturation. 24713123 15 19 theme inhibitors 2860:2869 arg1 models 2815:2820 in vivo models 2807:2820 in vivo models of hyperglycaemia and different HSP90 inhibitors 2807:2869 The results in this study should be confirmed using in vivo models of hyperglycaemia and different HSP90 inhibitors. 24713123 10 20 theme western 2013:2019 arg1 blot 2021:2024 western blot 2013:2024 western blot 2013:2024 MAIN RESULTS AND THE ROLE OF CHANCE Addition of the hyperglycaemic mimetic glucosamine to IVM medium for mouse COCs increased detectable O-GlcNAcylated protein levels (by western blot and immunocytochemistry), and this effect was reversed using an OGT inhibitor (P < 0.05). 24713123 15 21 theme HSP90 2854:2858 arg1 inhibitors 2860:2869 different HSP90 inhibitors 2844:2869 different HSP90 inhibitors 2844:2869 The results in this study should be confirmed using in vivo models of hyperglycaemia and different HSP90 inhibitors. 24713123 2 22 theme SUMMARY 312:318 arg1 protein 338:344 SUMMARY ANSWER Heat shock protein 90 312:347 SUMMARY ANSWER Heat shock protein 90 (HSP90) 312:355 SUMMARY ANSWER Heat shock protein 90 (HSP90) was identified and confirmed as being O-GlcNAcylated in mouse COCs under hyperglycaemic conditions (modelled using glucosamine), causing detrimental outcomes for embryo development. 24713123 2 22 theme SUMMARY 312:318 arg1 HSP90 350:354 HSP90 350:354 HSP90 350:354 SUMMARY ANSWER Heat shock protein 90 (HSP90) was identified and confirmed as being O-GlcNAcylated in mouse COCs under hyperglycaemic conditions (modelled using glucosamine), causing detrimental outcomes for embryo development. 24713123 9 23 theme Embryo 1745:1750 arg1 development 1752:1762 Embryo development 1745:1762 Embryo development 1745:1762 Embryo development was assessed using in vitro fertilization and embryo culture post-maturation. 24713123 6 24 theme PARTICIPANTS/MATERIALS 1267:1288 arg1 COCs 1308:1311 PARTICIPANTS/MATERIALS, SETTING, METHODS COCs 1267:1311 PARTICIPANTS/MATERIALS, SETTING, METHODS COCs from 21-day-old superovulated CBA × C57BL6 F1 hybrid female mice 1267:1376 PARTICIPANTS/MATERIALS, SETTING, METHODS COCs from 21-day-old superovulated CBA × C57BL6 F1 hybrid female mice were matured in vitro (IVM). 24713123 6 25 theme hybrid 1359:1364 arg1 mice 1373:1376 21-day-old superovulated CBA × C57BL6 F1 hybrid female mice 1318:1376 21-day-old superovulated CBA × C57BL6 F1 hybrid female mice 1318:1376 PARTICIPANTS/MATERIALS, SETTING, METHODS COCs from 21-day-old superovulated CBA × C57BL6 F1 hybrid female mice were matured in vitro (IVM). 24713123 3 26 theme increased 611:619 arg1 activity 621:628 increased activity 611:628 increased activity of the hexosamine biosynthesis pathway, which provides substrates for cumulus matrix production during COC maturation, and also for O-GlcNAcylation 611:776 WHAT IS KNOWN ALREADY O-GlcNAcylation of proteins occurs as a result of increased activity of the hexosamine biosynthesis pathway, which provides substrates for cumulus matrix production during COC maturation, and also for O-GlcNAcylation. 24713123 1 27 theme specific 225:232 arg1 proteins 234:241 specific proteins 225:241 specific proteins in the cumulus-oocyte complex (COC) 225:277 STUDY QUESTION What is the effect of beta-O-linked glycosylation (O-GlcNAcylation) on specific proteins in the cumulus-oocyte complex (COC) under hyperglycaemic conditions? 24713123 15 28 theme in 2807:2808 arg1 models 2815:2820 in vivo models 2807:2820 in vivo models of hyperglycaemia and different HSP90 inhibitors 2807:2869 The results in this study should be confirmed using in vivo models of hyperglycaemia and different HSP90 inhibitors. 24713123 6 29 theme C57BL6 1349:1354 arg1 mice 1373:1376 21-day-old superovulated CBA × C57BL6 F1 hybrid female mice 1318:1376 21-day-old superovulated CBA × C57BL6 F1 hybrid female mice 1318:1376 PARTICIPANTS/MATERIALS, SETTING, METHODS COCs from 21-day-old superovulated CBA × C57BL6 F1 hybrid female mice were matured in vitro (IVM). 24713123 18 30 theme funding 3289:3295 arg1 J.G.T. 3264:3269 J.G.T. 3264:3269 J.G.T. 3264:3269 J.G.T. is a recipient of funding from and a consultant to Cook Medical Pty Ltd. 24713123 18 30 theme funding 3289:3295 arg1 recipient 3276:3284 a recipient 3274:3284 a recipient of funding from and a consultant to Cook Medical Pty Ltd. 3274:3342 J.G.T. is a recipient of funding from and a consultant to Cook Medical Pty Ltd. 24713123 17 31 theme programme 3171:3179 arg1 Australia 3242:3250 Australia 3242:3250 Australia 3242:3250 STUDY FUNDING/COMPETING INTEREST(S) This work was supported by a programme grant from the National Health and Medical Research Council, Australia, ID 453556. 24713123 17 31 theme programme 3171:3179 arg1 453556 3256:3261 ID 453556 3253:3261 ID 453556 3253:3261 STUDY FUNDING/COMPETING INTEREST(S) This work was supported by a programme grant from the National Health and Medical Research Council, Australia, ID 453556. 24713123 17 31 theme programme 3171:3179 arg1 grant 3181:3185 a programme grant 3169:3185 a programme grant from the National Health and Medical Research Council 3169:3239 STUDY FUNDING/COMPETING INTEREST(S) This work was supported by a programme grant from the National Health and Medical Research Council, Australia, ID 453556. 24713123 6 32 theme CBA 1343:1345 arg1 mice 1373:1376 21-day-old superovulated CBA × C57BL6 F1 hybrid female mice 1318:1376 21-day-old superovulated CBA × C57BL6 F1 hybrid female mice 1318:1376 PARTICIPANTS/MATERIALS, SETTING, METHODS COCs from 21-day-old superovulated CBA × C57BL6 F1 hybrid female mice were matured in vitro (IVM). 24713123 3 33 theme hexosamine 637:646 arg1 pathway 661:667 the hexosamine biosynthesis pathway 633:667 the hexosamine biosynthesis pathway 633:667 WHAT IS KNOWN ALREADY O-GlcNAcylation of proteins occurs as a result of increased activity of the hexosamine biosynthesis pathway, which provides substrates for cumulus matrix production during COC maturation, and also for O-GlcNAcylation. 24713123 7 34 dep transferase 1461:1471 arg1 OGT 1474:1476 OGT 1474:1476 OGT 1474:1476 Levels of O-GlcNAcylated proteins, HSP90 and O-GlcNAc transferase (OGT, the enzyme responsible for O-GlcNAcylation) in COCs were measured using western blot, and localization observed using immunocytochemistry. 24713123 7 34 dep transferase 1461:1471 arg1 enzyme 1483:1488 the enzyme 1479:1488 the enzyme responsible for O-GlcNAcylation 1479:1520 Levels of O-GlcNAcylated proteins, HSP90 and O-GlcNAc transferase (OGT, the enzyme responsible for O-GlcNAcylation) in COCs were measured using western blot, and localization observed using immunocytochemistry. 24713123 4 35 contain have 824:827 arg1 COCs 779:782 COCs 779:782 COCs matured under hyperglycaemic conditions 779:822 COCs matured under hyperglycaemic conditions have decreased developmental competence, mediated at least in part through the mechanism of increased O-GlcNAcylation. 24713123 4 35 contain have 824:827 arg2 competence 853:862 decreased developmental competence 829:862 decreased developmental competence 829:862 COCs matured under hyperglycaemic conditions have decreased developmental competence, mediated at least in part through the mechanism of increased O-GlcNAcylation. 24713123 16 36 theme possible 3018:3025 arg1 interventions 3039:3051 possible therapeutic interventions 3018:3051 possible therapeutic interventions based on inhibiting HSP90 to improve oocyte quality 3018:3103 WIDER IMPLICATIONS OF THE FINDINGS This study leads to a new understanding of how diabetes influences oocyte competence and provides insight into possible therapeutic interventions based on inhibiting HSP90 to improve oocyte quality. 24713123 16 37 theme WIDER 2872:2876 arg1 IMPLICATIONS 2878:2889 WIDER IMPLICATIONS 2872:2889 WIDER IMPLICATIONS OF THE FINDINGS 2872:2905 WIDER IMPLICATIONS OF THE FINDINGS This study leads to a new understanding of how diabetes influences oocyte competence and provides insight into possible therapeutic interventions based on inhibiting HSP90 to improve oocyte quality. 24713123 5 38 theme STUDY 943:947 arg1 DESIGN 949:954 STUDY DESIGN 943:954 STUDY DESIGN 943:954 STUDY DESIGN, SIZE, DURATION This study was designed to examine the effect of hyperglycaemic conditions (using the hyperglycaemic mimetic, glucosamine) on O-GlcNAc levels in the mouse COC, and furthermore to identify potential candidate proteins which are targets of this modification, and their roles in oocyte maturation. 24713123 5 38 theme STUDY 943:947 arg1 DURATION 963:970 DURATION 963:970 DURATION 963:970 STUDY DESIGN, SIZE, DURATION This study was designed to examine the effect of hyperglycaemic conditions (using the hyperglycaemic mimetic, glucosamine) on O-GlcNAc levels in the mouse COC, and furthermore to identify potential candidate proteins which are targets of this modification, and their roles in oocyte maturation. 24713123 5 38 theme STUDY 943:947 arg1 SIZE 957:960 SIZE 957:960 SIZE 957:960 STUDY DESIGN, SIZE, DURATION This study was designed to examine the effect of hyperglycaemic conditions (using the hyperglycaemic mimetic, glucosamine) on O-GlcNAc levels in the mouse COC, and furthermore to identify potential candidate proteins which are targets of this modification, and their roles in oocyte maturation. 24713123 2 39 theme detrimental 494:504 arg1 outcomes 506:513 detrimental outcomes 494:513 detrimental outcomes for embryo development 494:536 SUMMARY ANSWER Heat shock protein 90 (HSP90) was identified and confirmed as being O-GlcNAcylated in mouse COCs under hyperglycaemic conditions (modelled using glucosamine), causing detrimental outcomes for embryo development. 24713123 16 40 theme FINDINGS 2898:2905 arg1 IMPLICATIONS 2878:2889 WIDER IMPLICATIONS 2872:2889 WIDER IMPLICATIONS OF THE FINDINGS 2872:2905 WIDER IMPLICATIONS OF THE FINDINGS This study leads to a new understanding of how diabetes influences oocyte competence and provides insight into possible therapeutic interventions based on inhibiting HSP90 to improve oocyte quality. 24713123 17 41 theme National 3196:3203 arg1 Health 3205:3210 the National Health 3192:3210 the National Health 3192:3210 STUDY FUNDING/COMPETING INTEREST(S) This work was supported by a programme grant from the National Health and Medical Research Council, Australia, ID 453556. 24713123 0 42 theme beta-O-linked 85:97 arg1 glycosylation 99:111 beta-O-linked glycosylation 85:111 beta-O-linked glycosylation of heat shock protein 90 85:136 Hyperglycaemic conditions perturb mouse oocyte in vitro developmental competence via beta-O-linked glycosylation of heat shock protein 90. 24713123 5 43 theme potential 1160:1168 arg1 proteins 1180:1187 potential candidate proteins 1160:1187 potential candidate proteins which are targets of this modification, and their roles in oocyte maturation 1160:1264 STUDY DESIGN, SIZE, DURATION This study was designed to examine the effect of hyperglycaemic conditions (using the hyperglycaemic mimetic, glucosamine) on O-GlcNAc levels in the mouse COC, and furthermore to identify potential candidate proteins which are targets of this modification, and their roles in oocyte maturation. 24713123 5 43 theme potential 1160:1168 arg1 targets 1199:1205 targets 1199:1205 targets of this modification 1199:1226 STUDY DESIGN, SIZE, DURATION This study was designed to examine the effect of hyperglycaemic conditions (using the hyperglycaemic mimetic, glucosamine) on O-GlcNAc levels in the mouse COC, and furthermore to identify potential candidate proteins which are targets of this modification, and their roles in oocyte maturation. 24713123 9 44 theme culture 1817:1823 arg1 post-maturation 1825:1839 embryo culture post-maturation 1810:1839 embryo culture post-maturation 1810:1839 Embryo development was assessed using in vitro fertilization and embryo culture post-maturation. 24713123 10 45 theme Addition 1878:1885 arg1 RESULTS 1847:1853 MAIN RESULTS 1842:1853 MAIN RESULTS 1842:1853 MAIN RESULTS AND THE ROLE OF CHANCE Addition of the hyperglycaemic mimetic glucosamine to IVM medium for mouse COCs increased detectable O-GlcNAcylated protein levels (by western blot and immunocytochemistry), and this effect was reversed using an OGT inhibitor (P < 0.05). 24713123 10 45 theme Addition 1878:1885 arg1 ROLE 1863:1866 THE ROLE 1859:1866 THE ROLE OF CHANCE Addition of the hyperglycaemic mimetic glucosamine to IVM medium for mouse COCs 1859:1956 MAIN RESULTS AND THE ROLE OF CHANCE Addition of the hyperglycaemic mimetic glucosamine to IVM medium for mouse COCs increased detectable O-GlcNAcylated protein levels (by western blot and immunocytochemistry), and this effect was reversed using an OGT inhibitor (P < 0.05). 24713123 9 46 dep in 1783:1784 arg1 vitro 1786:1790 vitro 1786:1790 vitro 1786:1790 Embryo development was assessed using in vitro fertilization and embryo culture post-maturation. 24713123 3 47 dep O-GlcNAcylation 561:575 arg1 proteins 580:587 proteins 580:587 proteins 580:587 WHAT IS KNOWN ALREADY O-GlcNAcylation of proteins occurs as a result of increased activity of the hexosamine biosynthesis pathway, which provides substrates for cumulus matrix production during COC maturation, and also for O-GlcNAcylation. 24713123 11 48 theme oocyte 2257:2262 arg1 competence 2278:2287 oocyte developmental competence 2257:2287 oocyte developmental competence (P < 0.05) 2257:2298 HSP90 was identified as a target of O-GlcNAcylation in the COC, and inhibition of HSP90 during IVM reversed glucosamine-induced decreases in oocyte developmental competence (P < 0.05). 24713123 11 48 theme oocyte 2257:2262 arg1 < 2292:2292 P < 0.05 2290:2297 P < 0.05 2290:2297 HSP90 was identified as a target of O-GlcNAcylation in the COC, and inhibition of HSP90 during IVM reversed glucosamine-induced decreases in oocyte developmental competence (P < 0.05). 24713123 0 49 theme shock 121:125 arg1 protein 127:133 heat shock protein 90 116:136 heat shock protein 90 116:136 Hyperglycaemic conditions perturb mouse oocyte in vitro developmental competence via beta-O-linked glycosylation of heat shock protein 90. 24713123 0 50 gly glycosylation 99:111 arg1 protein 127:133 heat shock protein 90 116:136 heat shock protein 90 116:136 Hyperglycaemic conditions perturb mouse oocyte in vitro developmental competence via beta-O-linked glycosylation of heat shock protein 90. 24713123 5 51 dep DESIGN 949:954 arg1 designed 987:994 designed 987:994 was designed to examine the effect of hyperglycaemic conditions (using the hyperglycaemic mimetic, glucosamine) on O-GlcNAc levels in the mouse COC, and furthermore to identify potential candidate proteins which are targets of this modification, and their roles in oocyte maturation 983:1264 STUDY DESIGN, SIZE, DURATION This study was designed to examine the effect of hyperglycaemic conditions (using the hyperglycaemic mimetic, glucosamine) on O-GlcNAc levels in the mouse COC, and furthermore to identify potential candidate proteins which are targets of this modification, and their roles in oocyte maturation. 24713123 0 52 theme Hyperglycaemic 0:13 arg1 conditions 15:24 Hyperglycaemic conditions 0:24 Hyperglycaemic conditions 0:24 Hyperglycaemic conditions perturb mouse oocyte in vitro developmental competence via beta-O-linked glycosylation of heat shock protein 90. 24713123 14 53 theme O-GlcNAc 2736:2743 arg1 moieties 2745:2752 the O-GlcNAc moieties 2732:2752 the O-GlcNAc moieties 2732:2752 Additionally, glucosamine, a hyperglycaemic mimetic, was used because it specifically activates the hexosamine pathway which provides the O-GlcNAc moieties. 24713123 10 54 theme CHANCE 1871:1876 arg1 Addition 1878:1885 CHANCE Addition 1871:1885 CHANCE Addition of the hyperglycaemic mimetic glucosamine to IVM medium 1871:1941 MAIN RESULTS AND THE ROLE OF CHANCE Addition of the hyperglycaemic mimetic glucosamine to IVM medium for mouse COCs increased detectable O-GlcNAcylated protein levels (by western blot and immunocytochemistry), and this effect was reversed using an OGT inhibitor (P < 0.05). 24713123 16 55 theme oocyte 2974:2979 arg1 competence 2981:2990 oocyte competence 2974:2990 oocyte competence 2974:2990 WIDER IMPLICATIONS OF THE FINDINGS This study leads to a new understanding of how diabetes influences oocyte competence and provides insight into possible therapeutic interventions based on inhibiting HSP90 to improve oocyte quality. 24713123 5 56 theme modification 1215:1226 arg1 roles 1239:1243 their roles 1233:1243 their roles in oocyte maturation 1233:1264 STUDY DESIGN, SIZE, DURATION This study was designed to examine the effect of hyperglycaemic conditions (using the hyperglycaemic mimetic, glucosamine) on O-GlcNAc levels in the mouse COC, and furthermore to identify potential candidate proteins which are targets of this modification, and their roles in oocyte maturation. 24713123 5 56 theme modification 1215:1226 arg1 proteins 1180:1187 potential candidate proteins 1160:1187 potential candidate proteins which are targets of this modification, and their roles in oocyte maturation 1160:1264 STUDY DESIGN, SIZE, DURATION This study was designed to examine the effect of hyperglycaemic conditions (using the hyperglycaemic mimetic, glucosamine) on O-GlcNAc levels in the mouse COC, and furthermore to identify potential candidate proteins which are targets of this modification, and their roles in oocyte maturation. 24713123 5 56 theme modification 1215:1226 arg1 targets 1199:1205 targets 1199:1205 targets of this modification 1199:1226 STUDY DESIGN, SIZE, DURATION This study was designed to examine the effect of hyperglycaemic conditions (using the hyperglycaemic mimetic, glucosamine) on O-GlcNAc levels in the mouse COC, and furthermore to identify potential candidate proteins which are targets of this modification, and their roles in oocyte maturation. 24713123 7 57 theme western 1551:1557 arg1 blot 1559:1562 western blot 1551:1562 western blot 1551:1562 Levels of O-GlcNAcylated proteins, HSP90 and O-GlcNAc transferase (OGT, the enzyme responsible for O-GlcNAcylation) in COCs were measured using western blot, and localization observed using immunocytochemistry. 24713123 13 58 theme LIMITATIONS 2442:2452 arg1 maturation 2484:2493 LIMITATIONS, REASONS FOR CAUTION In vitro maturation 2442:2493 LIMITATIONS, REASONS FOR CAUTION In vitro maturation of COCs 2442:2501 LIMITATIONS, REASONS FOR CAUTION In vitro maturation of COCs was used so that treatment time could be limited to the 17 h of maturation prior to ovulation. 24713123 10 59 theme mimetic 1909:1915 arg1 glucosamine 1917:1927 the hyperglycaemic mimetic glucosamine 1890:1927 the hyperglycaemic mimetic glucosamine 1890:1927 MAIN RESULTS AND THE ROLE OF CHANCE Addition of the hyperglycaemic mimetic glucosamine to IVM medium for mouse COCs increased detectable O-GlcNAcylated protein levels (by western blot and immunocytochemistry), and this effect was reversed using an OGT inhibitor (P < 0.05). 24713123 18 60 from Ltd. 3339:3342 arg1 J.G.T. 3264:3269 J.G.T. 3264:3269 J.G.T. 3264:3269 J.G.T. is a recipient of funding from and a consultant to Cook Medical Pty Ltd. 24713123 18 60 from Ltd. 3339:3342 arg1 recipient 3276:3284 a recipient 3274:3284 a recipient of funding from and a consultant to Cook Medical Pty Ltd. 3274:3342 J.G.T. is a recipient of funding from and a consultant to Cook Medical Pty Ltd. 24713123 2 61 theme mouse 413:417 arg1 COCs 419:422 mouse COCs 413:422 mouse COCs 413:422 SUMMARY ANSWER Heat shock protein 90 (HSP90) was identified and confirmed as being O-GlcNAcylated in mouse COCs under hyperglycaemic conditions (modelled using glucosamine), causing detrimental outcomes for embryo development. 24713123 0 62 theme oocyte 40:45 arg1 competence 70:79 mouse oocyte in vitro developmental competence 34:79 mouse oocyte in vitro developmental competence 34:79 Hyperglycaemic conditions perturb mouse oocyte in vitro developmental competence via beta-O-linked glycosylation of heat shock protein 90. 24713123 12 63 from finding 2332:2338 arg1 COCs 2383:2386 COCs 2383:2386 COCs 2383:2386 We also demonstrated the novel finding of an association between HSP90 and OGT in COCs, suggesting a possible client-chaperone relationship. 24713123 12 64 theme client-chaperone 2411:2426 arg1 relationship 2428:2439 a possible client-chaperone relationship 2400:2439 a possible client-chaperone relationship 2400:2439 We also demonstrated the novel finding of an association between HSP90 and OGT in COCs, suggesting a possible client-chaperone relationship. 24713123 3 65 theme pathway 661:667 arg1 activity 621:628 increased activity 611:628 increased activity of the hexosamine biosynthesis pathway, which provides substrates for cumulus matrix production during COC maturation, and also for O-GlcNAcylation 611:776 WHAT IS KNOWN ALREADY O-GlcNAcylation of proteins occurs as a result of increased activity of the hexosamine biosynthesis pathway, which provides substrates for cumulus matrix production during COC maturation, and also for O-GlcNAcylation. 24713123 17 66 theme INTEREST 3130:3137 arg1 S 3139:3139 STUDY FUNDING/COMPETING INTEREST(S) 3106:3140 STUDY FUNDING/COMPETING INTEREST(S) This work was supported by a programme grant from the National Health and Medical Research Council, Australia, ID 453556. 3106:3262 STUDY FUNDING/COMPETING INTEREST(S) This work was supported by a programme grant from the National Health and Medical Research Council, Australia, ID 453556. 24713123 13 67 theme maturation 2567:2576 arg1 h 2562:2562 the 17 h 2555:2562 the 17 h of maturation prior to ovulation 2555:2595 LIMITATIONS, REASONS FOR CAUTION In vitro maturation of COCs was used so that treatment time could be limited to the 17 h of maturation prior to ovulation. 24713123 16 68 theme new 2929:2931 arg1 understanding 2933:2945 a new understanding 2927:2945 a new understanding of how diabetes influences oocyte competence and provides insight into possible therapeutic interventions based on inhibiting HSP90 to improve oocyte quality 2927:3103 WIDER IMPLICATIONS OF THE FINDINGS This study leads to a new understanding of how diabetes influences oocyte competence and provides insight into possible therapeutic interventions based on inhibiting HSP90 to improve oocyte quality. 24713123 2 69 from O-GlcNAcylated 395:408 arg1 COCs 419:422 mouse COCs 413:422 mouse COCs 413:422 SUMMARY ANSWER Heat shock protein 90 (HSP90) was identified and confirmed as being O-GlcNAcylated in mouse COCs under hyperglycaemic conditions (modelled using glucosamine), causing detrimental outcomes for embryo development. 24713123 10 70 theme hyperglycaemic 1894:1907 arg1 glucosamine 1917:1927 the hyperglycaemic mimetic glucosamine 1890:1927 the hyperglycaemic mimetic glucosamine 1890:1927 MAIN RESULTS AND THE ROLE OF CHANCE Addition of the hyperglycaemic mimetic glucosamine to IVM medium for mouse COCs increased detectable O-GlcNAcylated protein levels (by western blot and immunocytochemistry), and this effect was reversed using an OGT inhibitor (P < 0.05). 24713123 10 71 dep increased 1958:1966 arg1 blot 2021:2024 western blot 2013:2024 western blot 2013:2024 MAIN RESULTS AND THE ROLE OF CHANCE Addition of the hyperglycaemic mimetic glucosamine to IVM medium for mouse COCs increased detectable O-GlcNAcylated protein levels (by western blot and immunocytochemistry), and this effect was reversed using an OGT inhibitor (P < 0.05). 24713123 10 71 dep increased 1958:1966 arg1 immunocytochemistry 2030:2048 immunocytochemistry 2030:2048 immunocytochemistry 2030:2048 MAIN RESULTS AND THE ROLE OF CHANCE Addition of the hyperglycaemic mimetic glucosamine to IVM medium for mouse COCs increased detectable O-GlcNAcylated protein levels (by western blot and immunocytochemistry), and this effect was reversed using an OGT inhibitor (P < 0.05). 24713123 3 72 theme cumulus 700:706 arg1 production 715:724 cumulus matrix production 700:724 cumulus matrix production during COC maturation 700:746 WHAT IS KNOWN ALREADY O-GlcNAcylation of proteins occurs as a result of increased activity of the hexosamine biosynthesis pathway, which provides substrates for cumulus matrix production during COC maturation, and also for O-GlcNAcylation. 24713123 4 73 theme decreased 829:837 arg1 competence 853:862 decreased developmental competence 829:862 decreased developmental competence 829:862 COCs matured under hyperglycaemic conditions have decreased developmental competence, mediated at least in part through the mechanism of increased O-GlcNAcylation. 24713123 14 74 used used 2655:2658 arg2 mimetic 2642:2648 mimetic 2642:2648 mimetic 2642:2648 Additionally, glucosamine, a hyperglycaemic mimetic, was used because it specifically activates the hexosamine pathway which provides the O-GlcNAc moieties. 24713123 14 74 used used 2655:2658 arg2 glucosamine 2612:2622 glucosamine 2612:2622 glucosamine 2612:2622 Additionally, glucosamine, a hyperglycaemic mimetic, was used because it specifically activates the hexosamine pathway which provides the O-GlcNAc moieties. 24713123 5 75 theme oocyte 1248:1253 arg1 maturation 1255:1264 oocyte maturation 1248:1264 oocyte maturation 1248:1264 STUDY DESIGN, SIZE, DURATION This study was designed to examine the effect of hyperglycaemic conditions (using the hyperglycaemic mimetic, glucosamine) on O-GlcNAc levels in the mouse COC, and furthermore to identify potential candidate proteins which are targets of this modification, and their roles in oocyte maturation. 24713123 5 76 theme conditions 1036:1045 arg1 effect 1011:1016 the effect 1007:1016 the effect of hyperglycaemic conditions (using the hyperglycaemic mimetic, glucosamine) on O-GlcNAc levels in the mouse COC 1007:1129 STUDY DESIGN, SIZE, DURATION This study was designed to examine the effect of hyperglycaemic conditions (using the hyperglycaemic mimetic, glucosamine) on O-GlcNAc levels in the mouse COC, and furthermore to identify potential candidate proteins which are targets of this modification, and their roles in oocyte maturation. 24713123 10 77 theme P 2105:2105 arg1 < 2107:2107 P < 0.05 2105:2112 P < 0.05 2105:2112 MAIN RESULTS AND THE ROLE OF CHANCE Addition of the hyperglycaemic mimetic glucosamine to IVM medium for mouse COCs increased detectable O-GlcNAcylated protein levels (by western blot and immunocytochemistry), and this effect was reversed using an OGT inhibitor (P < 0.05). 24713123 10 77 theme P 2105:2105 arg1 inhibitor 2094:2102 an OGT inhibitor 2087:2102 an OGT inhibitor (P < 0.05) 2087:2113 MAIN RESULTS AND THE ROLE OF CHANCE Addition of the hyperglycaemic mimetic glucosamine to IVM medium for mouse COCs increased detectable O-GlcNAcylated protein levels (by western blot and immunocytochemistry), and this effect was reversed using an OGT inhibitor (P < 0.05). 24713123 8 78 theme glycosylated 1622:1633 arg1 levels 1641:1646 glycosylated HSP90 levels 1622:1646 glycosylated HSP90 levels 1622:1646 For glycosylated HSP90 levels, and to test OGT-HSP90 interaction, immunoprecipitation was performed prior to western blotting. 24713123 17 79 dep S 3139:3139 arg1 supported 3156:3164 supported 3156:3164 was supported by a programme grant from the National Health and Medical Research Council, Australia, ID 453556 3152:3261 STUDY FUNDING/COMPETING INTEREST(S) This work was supported by a programme grant from the National Health and Medical Research Council, Australia, ID 453556. 24713123 15 80 theme different 2844:2852 arg1 inhibitors 2860:2869 different HSP90 inhibitors 2844:2869 different HSP90 inhibitors 2844:2869 The results in this study should be confirmed using in vivo models of hyperglycaemia and different HSP90 inhibitors. 24713123 3 81 theme COC 733:735 arg1 maturation 737:746 COC maturation 733:746 COC maturation 733:746 WHAT IS KNOWN ALREADY O-GlcNAcylation of proteins occurs as a result of increased activity of the hexosamine biosynthesis pathway, which provides substrates for cumulus matrix production during COC maturation, and also for O-GlcNAcylation. 24713123 6 82 theme superovulated 1329:1341 arg1 CBA 1343:1345 21-day-old superovulated CBA × 1318:1347 21-day-old superovulated CBA × C57BL6 F1 hybrid female mice 1318:1376 PARTICIPANTS/MATERIALS, SETTING, METHODS COCs from 21-day-old superovulated CBA × C57BL6 F1 hybrid female mice were matured in vitro (IVM). 24713123 19 83 theme other 3348:3352 arg1 authors 3354:3360 The other authors 3344:3360 The other authors 3344:3360 The other authors have no conflicts of interest to declare. 24713123 15 84 dep in 2807:2808 arg1 vivo 2810:2813 vivo 2810:2813 vivo 2810:2813 The results in this study should be confirmed using in vivo models of hyperglycaemia and different HSP90 inhibitors. 24713123 10 85 theme mouse 1947:1951 arg1 COCs 1953:1956 mouse COCs 1947:1956 mouse COCs 1947:1956 MAIN RESULTS AND THE ROLE OF CHANCE Addition of the hyperglycaemic mimetic glucosamine to IVM medium for mouse COCs increased detectable O-GlcNAcylated protein levels (by western blot and immunocytochemistry), and this effect was reversed using an OGT inhibitor (P < 0.05). 24713123 10 86 theme MAIN 1842:1845 arg1 RESULTS 1847:1853 MAIN RESULTS 1842:1853 MAIN RESULTS 1842:1853 MAIN RESULTS AND THE ROLE OF CHANCE Addition of the hyperglycaemic mimetic glucosamine to IVM medium for mouse COCs increased detectable O-GlcNAcylated protein levels (by western blot and immunocytochemistry), and this effect was reversed using an OGT inhibitor (P < 0.05). 24713123 4 87 theme increased 916:924 arg1 O-GlcNAcylation 926:940 increased O-GlcNAcylation 916:940 increased O-GlcNAcylation 916:940 COCs matured under hyperglycaemic conditions have decreased developmental competence, mediated at least in part through the mechanism of increased O-GlcNAcylation. 24713123 17 88 theme FUNDING/COMPETING 3112:3128 arg1 S 3139:3139 STUDY FUNDING/COMPETING INTEREST(S) 3106:3140 STUDY FUNDING/COMPETING INTEREST(S) This work was supported by a programme grant from the National Health and Medical Research Council, Australia, ID 453556. 3106:3262 STUDY FUNDING/COMPETING INTEREST(S) This work was supported by a programme grant from the National Health and Medical Research Council, Australia, ID 453556. 24713123 11 89 theme P 2290:2290 arg1 competence 2278:2287 oocyte developmental competence 2257:2287 oocyte developmental competence (P < 0.05) 2257:2298 HSP90 was identified as a target of O-GlcNAcylation in the COC, and inhibition of HSP90 during IVM reversed glucosamine-induced decreases in oocyte developmental competence (P < 0.05). 24713123 11 89 theme P 2290:2290 arg1 < 2292:2292 P < 0.05 2290:2297 P < 0.05 2290:2297 HSP90 was identified as a target of O-GlcNAcylation in the COC, and inhibition of HSP90 during IVM reversed glucosamine-induced decreases in oocyte developmental competence (P < 0.05). 24713123 10 90 theme O-GlcNAcylated 1979:1992 arg1 levels 2002:2007 detectable O-GlcNAcylated protein levels 1968:2007 detectable O-GlcNAcylated protein levels 1968:2007 MAIN RESULTS AND THE ROLE OF CHANCE Addition of the hyperglycaemic mimetic glucosamine to IVM medium for mouse COCs increased detectable O-GlcNAcylated protein levels (by western blot and immunocytochemistry), and this effect was reversed using an OGT inhibitor (P < 0.05). 24713123 2 91 theme shock 332:336 arg1 protein 338:344 SUMMARY ANSWER Heat shock protein 90 312:347 SUMMARY ANSWER Heat shock protein 90 (HSP90) 312:355 SUMMARY ANSWER Heat shock protein 90 (HSP90) was identified and confirmed as being O-GlcNAcylated in mouse COCs under hyperglycaemic conditions (modelled using glucosamine), causing detrimental outcomes for embryo development. 24713123 2 91 theme shock 332:336 arg1 HSP90 350:354 HSP90 350:354 HSP90 350:354 SUMMARY ANSWER Heat shock protein 90 (HSP90) was identified and confirmed as being O-GlcNAcylated in mouse COCs under hyperglycaemic conditions (modelled using glucosamine), causing detrimental outcomes for embryo development. 24713123 1 92 theme glycosylation 190:202 arg1 QUESTION 145:152 STUDY QUESTION 139:152 STUDY QUESTION What is the effect of beta-O-linked glycosylation (O-GlcNAcylation) on specific proteins in the cumulus-oocyte complex (COC) under hyperglycaemic conditions? 139:310 STUDY QUESTION What is the effect of beta-O-linked glycosylation (O-GlcNAcylation) on specific proteins in the cumulus-oocyte complex (COC) under hyperglycaemic conditions? 24713123 1 92 theme glycosylation 190:202 arg1 effect 166:171 the effect 162:171 the effect of beta-O-linked glycosylation (O-GlcNAcylation) on specific proteins in the cumulus-oocyte complex (COC) 162:277 STUDY QUESTION What is the effect of beta-O-linked glycosylation (O-GlcNAcylation) on specific proteins in the cumulus-oocyte complex (COC) under hyperglycaemic conditions? 24713123 11 93 theme O-GlcNAcylation 2152:2166 arg1 decreases 2244:2252 glucosamine-induced decreases 2224:2252 glucosamine-induced decreases in oocyte developmental competence (P < 0.05) 2224:2298 HSP90 was identified as a target of O-GlcNAcylation in the COC, and inhibition of HSP90 during IVM reversed glucosamine-induced decreases in oocyte developmental competence (P < 0.05). 24713123 11 93 theme O-GlcNAcylation 2152:2166 arg1 target 2142:2147 a target 2140:2147 a target of O-GlcNAcylation in the COC 2140:2177 HSP90 was identified as a target of O-GlcNAcylation in the COC, and inhibition of HSP90 during IVM reversed glucosamine-induced decreases in oocyte developmental competence (P < 0.05). 24713123 11 93 theme O-GlcNAcylation 2152:2166 arg1 HSP90 2116:2120 HSP90 2116:2120 HSP90 2116:2120 HSP90 was identified as a target of O-GlcNAcylation in the COC, and inhibition of HSP90 during IVM reversed glucosamine-induced decreases in oocyte developmental competence (P < 0.05). 24713123 5 94 from roles 1239:1243 arg1 maturation 1255:1264 oocyte maturation 1248:1264 oocyte maturation 1248:1264 STUDY DESIGN, SIZE, DURATION This study was designed to examine the effect of hyperglycaemic conditions (using the hyperglycaemic mimetic, glucosamine) on O-GlcNAc levels in the mouse COC, and furthermore to identify potential candidate proteins which are targets of this modification, and their roles in oocyte maturation. 24713123 2 95 theme ANSWER 320:325 arg1 protein 338:344 SUMMARY ANSWER Heat shock protein 90 312:347 SUMMARY ANSWER Heat shock protein 90 (HSP90) 312:355 SUMMARY ANSWER Heat shock protein 90 (HSP90) was identified and confirmed as being O-GlcNAcylated in mouse COCs under hyperglycaemic conditions (modelled using glucosamine), causing detrimental outcomes for embryo development. 24713123 2 95 theme ANSWER 320:325 arg1 HSP90 350:354 HSP90 350:354 HSP90 350:354 SUMMARY ANSWER Heat shock protein 90 (HSP90) was identified and confirmed as being O-GlcNAcylated in mouse COCs under hyperglycaemic conditions (modelled using glucosamine), causing detrimental outcomes for embryo development. 24713123 12 96 theme association 2346:2356 arg1 finding 2332:2338 the novel finding 2322:2338 the novel finding of an association between HSP90 and OGT in COCs 2322:2386 We also demonstrated the novel finding of an association between HSP90 and OGT in COCs, suggesting a possible client-chaperone relationship. 24713123 7 97 theme O-GlcNAcylated 1417:1430 arg1 proteins 1432:1439 O-GlcNAcylated proteins 1417:1439 O-GlcNAcylated proteins 1417:1439 Levels of O-GlcNAcylated proteins, HSP90 and O-GlcNAc transferase (OGT, the enzyme responsible for O-GlcNAcylation) in COCs were measured using western blot, and localization observed using immunocytochemistry. 24713123 7 97 theme O-GlcNAcylated 1417:1430 arg1 HSP90 1442:1446 HSP90 1442:1446 HSP90 1442:1446 Levels of O-GlcNAcylated proteins, HSP90 and O-GlcNAc transferase (OGT, the enzyme responsible for O-GlcNAcylation) in COCs were measured using western blot, and localization observed using immunocytochemistry. 24713123 7 97 theme O-GlcNAcylated 1417:1430 arg1 transferase 1461:1471 O-GlcNAc transferase 1452:1471 O-GlcNAc transferase (OGT, the enzyme responsible for O-GlcNAcylation) 1452:1521 Levels of O-GlcNAcylated proteins, HSP90 and O-GlcNAc transferase (OGT, the enzyme responsible for O-GlcNAcylation) in COCs were measured using western blot, and localization observed using immunocytochemistry. 24713123 11 98 theme glucosamine-induced 2224:2242 arg1 decreases 2244:2252 glucosamine-induced decreases 2224:2252 glucosamine-induced decreases in oocyte developmental competence (P < 0.05) 2224:2298 HSP90 was identified as a target of O-GlcNAcylation in the COC, and inhibition of HSP90 during IVM reversed glucosamine-induced decreases in oocyte developmental competence (P < 0.05). 24713123 11 98 theme glucosamine-induced 2224:2242 arg1 target 2142:2147 a target 2140:2147 a target of O-GlcNAcylation in the COC 2140:2177 HSP90 was identified as a target of O-GlcNAcylation in the COC, and inhibition of HSP90 during IVM reversed glucosamine-induced decreases in oocyte developmental competence (P < 0.05). 24713123 11 98 theme glucosamine-induced 2224:2242 arg1 HSP90 2116:2120 HSP90 2116:2120 HSP90 2116:2120 HSP90 was identified as a target of O-GlcNAcylation in the COC, and inhibition of HSP90 during IVM reversed glucosamine-induced decreases in oocyte developmental competence (P < 0.05). 24713123 6 99 theme female 1366:1371 arg1 mice 1373:1376 21-day-old superovulated CBA × C57BL6 F1 hybrid female mice 1318:1376 21-day-old superovulated CBA × C57BL6 F1 hybrid female mice 1318:1376 PARTICIPANTS/MATERIALS, SETTING, METHODS COCs from 21-day-old superovulated CBA × C57BL6 F1 hybrid female mice were matured in vitro (IVM). 24713123 13 100 used used 2507:2510 arg2 maturation 2484:2493 LIMITATIONS, REASONS FOR CAUTION In vitro maturation 2442:2493 LIMITATIONS, REASONS FOR CAUTION In vitro maturation of COCs 2442:2501 LIMITATIONS, REASONS FOR CAUTION In vitro maturation of COCs was used so that treatment time could be limited to the 17 h of maturation prior to ovulation. 24713123 5 101 dep conditions 1036:1045 arg1 using 1048:1052 using 1048:1052 using the hyperglycaemic mimetic, glucosamine 1048:1092 STUDY DESIGN, SIZE, DURATION This study was designed to examine the effect of hyperglycaemic conditions (using the hyperglycaemic mimetic, glucosamine) on O-GlcNAc levels in the mouse COC, and furthermore to identify potential candidate proteins which are targets of this modification, and their roles in oocyte maturation. 24713123 17 102 theme ID 3253:3254 arg1 453556 3256:3261 ID 453556 3253:3261 ID 453556 3253:3261 STUDY FUNDING/COMPETING INTEREST(S) This work was supported by a programme grant from the National Health and Medical Research Council, Australia, ID 453556. 24713123 17 102 theme ID 3253:3254 arg1 grant 3181:3185 a programme grant 3169:3185 a programme grant from the National Health and Medical Research Council 3169:3239 STUDY FUNDING/COMPETING INTEREST(S) This work was supported by a programme grant from the National Health and Medical Research Council, Australia, ID 453556. 24713123 6 103 theme F1 1356:1357 arg1 mice 1373:1376 21-day-old superovulated CBA × C57BL6 F1 hybrid female mice 1318:1376 21-day-old superovulated CBA × C57BL6 F1 hybrid female mice 1318:1376 PARTICIPANTS/MATERIALS, SETTING, METHODS COCs from 21-day-old superovulated CBA × C57BL6 F1 hybrid female mice were matured in vitro (IVM). 24713123 5 104 theme mouse 1121:1125 arg1 COC 1127:1129 the mouse COC 1117:1129 the mouse COC 1117:1129 STUDY DESIGN, SIZE, DURATION This study was designed to examine the effect of hyperglycaemic conditions (using the hyperglycaemic mimetic, glucosamine) on O-GlcNAc levels in the mouse COC, and furthermore to identify potential candidate proteins which are targets of this modification, and their roles in oocyte maturation. 24713123 17 105 from Health 3205:3210 arg1 Australia 3242:3250 Australia 3242:3250 Australia 3242:3250 STUDY FUNDING/COMPETING INTEREST(S) This work was supported by a programme grant from the National Health and Medical Research Council, Australia, ID 453556. 24713123 17 105 from Health 3205:3210 arg1 453556 3256:3261 ID 453556 3253:3261 ID 453556 3253:3261 STUDY FUNDING/COMPETING INTEREST(S) This work was supported by a programme grant from the National Health and Medical Research Council, Australia, ID 453556. 24713123 17 105 from Health 3205:3210 arg1 grant 3181:3185 a programme grant 3169:3185 a programme grant from the National Health and Medical Research Council 3169:3239 STUDY FUNDING/COMPETING INTEREST(S) This work was supported by a programme grant from the National Health and Medical Research Council, Australia, ID 453556. 24713123 13 106 theme COCs 2498:2501 arg1 maturation 2484:2493 LIMITATIONS, REASONS FOR CAUTION In vitro maturation 2442:2493 LIMITATIONS, REASONS FOR CAUTION In vitro maturation of COCs 2442:2501 LIMITATIONS, REASONS FOR CAUTION In vitro maturation of COCs was used so that treatment time could be limited to the 17 h of maturation prior to ovulation. 24713123 12 107 theme novel 2326:2330 arg1 finding 2332:2338 the novel finding 2322:2338 the novel finding of an association between HSP90 and OGT in COCs 2322:2386 We also demonstrated the novel finding of an association between HSP90 and OGT in COCs, suggesting a possible client-chaperone relationship. 24713123 11 108 from target 2142:2147 arg1 COC 2175:2177 the COC 2171:2177 the COC 2171:2177 HSP90 was identified as a target of O-GlcNAcylation in the COC, and inhibition of HSP90 during IVM reversed glucosamine-induced decreases in oocyte developmental competence (P < 0.05). 24713123 1 109 from proteins 234:241 arg1 COC 274:276 COC 274:276 COC 274:276 STUDY QUESTION What is the effect of beta-O-linked glycosylation (O-GlcNAcylation) on specific proteins in the cumulus-oocyte complex (COC) under hyperglycaemic conditions? 24713123 1 109 from proteins 234:241 arg1 complex 265:271 cumulus-oocyte complex 250:271 the cumulus-oocyte complex (COC) 246:277 STUDY QUESTION What is the effect of beta-O-linked glycosylation (O-GlcNAcylation) on specific proteins in the cumulus-oocyte complex (COC) under hyperglycaemic conditions? 24713123 1 110 theme STUDY 139:143 arg1 QUESTION 145:152 STUDY QUESTION 139:152 STUDY QUESTION What is the effect of beta-O-linked glycosylation (O-GlcNAcylation) on specific proteins in the cumulus-oocyte complex (COC) under hyperglycaemic conditions? 139:310 STUDY QUESTION What is the effect of beta-O-linked glycosylation (O-GlcNAcylation) on specific proteins in the cumulus-oocyte complex (COC) under hyperglycaemic conditions? 24713123 1 110 theme STUDY 139:143 arg1 effect 166:171 the effect 162:171 the effect of beta-O-linked glycosylation (O-GlcNAcylation) on specific proteins in the cumulus-oocyte complex (COC) 162:277 STUDY QUESTION What is the effect of beta-O-linked glycosylation (O-GlcNAcylation) on specific proteins in the cumulus-oocyte complex (COC) under hyperglycaemic conditions? 24713123 9 111 theme in 1783:1784 arg1 fertilization 1792:1804 in vitro fertilization 1783:1804 in vitro fertilization 1783:1804 Embryo development was assessed using in vitro fertilization and embryo culture post-maturation. 24713123 16 112 theme therapeutic 3027:3037 arg1 interventions 3039:3051 possible therapeutic interventions 3018:3051 possible therapeutic interventions based on inhibiting HSP90 to improve oocyte quality 3018:3103 WIDER IMPLICATIONS OF THE FINDINGS This study leads to a new understanding of how diabetes influences oocyte competence and provides insight into possible therapeutic interventions based on inhibiting HSP90 to improve oocyte quality. 24713123 5 113 theme O-GlcNAc 1098:1105 arg1 levels 1107:1112 O-GlcNAc levels 1098:1112 O-GlcNAc levels in the mouse COC 1098:1129 STUDY DESIGN, SIZE, DURATION This study was designed to examine the effect of hyperglycaemic conditions (using the hyperglycaemic mimetic, glucosamine) on O-GlcNAc levels in the mouse COC, and furthermore to identify potential candidate proteins which are targets of this modification, and their roles in oocyte maturation. 24713123 3 114 theme activity 621:628 arg1 result 601:606 a result 599:606 a result of increased activity of the hexosamine biosynthesis pathway, which provides substrates for cumulus matrix production during COC maturation, and also for O-GlcNAcylation 599:776 WHAT IS KNOWN ALREADY O-GlcNAcylation of proteins occurs as a result of increased activity of the hexosamine biosynthesis pathway, which provides substrates for cumulus matrix production during COC maturation, and also for O-GlcNAcylation. 24713123 9 115 theme embryo 1810:1815 arg1 post-maturation 1825:1839 embryo culture post-maturation 1810:1839 embryo culture post-maturation 1810:1839 Embryo development was assessed using in vitro fertilization and embryo culture post-maturation. 24713123 11 116 from decreases 2244:2252 arg1 competence 2278:2287 oocyte developmental competence 2257:2287 oocyte developmental competence (P < 0.05) 2257:2298 HSP90 was identified as a target of O-GlcNAcylation in the COC, and inhibition of HSP90 during IVM reversed glucosamine-induced decreases in oocyte developmental competence (P < 0.05). 24713123 11 116 from decreases 2244:2252 arg1 < 2292:2292 P < 0.05 2290:2297 P < 0.05 2290:2297 HSP90 was identified as a target of O-GlcNAcylation in the COC, and inhibition of HSP90 during IVM reversed glucosamine-induced decreases in oocyte developmental competence (P < 0.05). 24713123 10 117 theme OGT 2090:2092 arg1 < 2107:2107 P < 0.05 2105:2112 P < 0.05 2105:2112 MAIN RESULTS AND THE ROLE OF CHANCE Addition of the hyperglycaemic mimetic glucosamine to IVM medium for mouse COCs increased detectable O-GlcNAcylated protein levels (by western blot and immunocytochemistry), and this effect was reversed using an OGT inhibitor (P < 0.05). 24713123 10 117 theme OGT 2090:2092 arg1 inhibitor 2094:2102 an OGT inhibitor 2087:2102 an OGT inhibitor (P < 0.05) 2087:2113 MAIN RESULTS AND THE ROLE OF CHANCE Addition of the hyperglycaemic mimetic glucosamine to IVM medium for mouse COCs increased detectable O-GlcNAcylated protein levels (by western blot and immunocytochemistry), and this effect was reversed using an OGT inhibitor (P < 0.05). 24713123 0 118 theme heat 116:119 arg1 protein 127:133 heat shock protein 90 116:136 heat shock protein 90 116:136 Hyperglycaemic conditions perturb mouse oocyte in vitro developmental competence via beta-O-linked glycosylation of heat shock protein 90. 24713123 5 119 theme candidate 1170:1178 arg1 proteins 1180:1187 potential candidate proteins 1160:1187 potential candidate proteins which are targets of this modification, and their roles in oocyte maturation 1160:1264 STUDY DESIGN, SIZE, DURATION This study was designed to examine the effect of hyperglycaemic conditions (using the hyperglycaemic mimetic, glucosamine) on O-GlcNAc levels in the mouse COC, and furthermore to identify potential candidate proteins which are targets of this modification, and their roles in oocyte maturation. 24713123 5 119 theme candidate 1170:1178 arg1 targets 1199:1205 targets 1199:1205 targets of this modification 1199:1226 STUDY DESIGN, SIZE, DURATION This study was designed to examine the effect of hyperglycaemic conditions (using the hyperglycaemic mimetic, glucosamine) on O-GlcNAc levels in the mouse COC, and furthermore to identify potential candidate proteins which are targets of this modification, and their roles in oocyte maturation. 24713123 1 120 from effect 166:171 arg1 proteins 234:241 specific proteins 225:241 specific proteins in the cumulus-oocyte complex (COC) 225:277 STUDY QUESTION What is the effect of beta-O-linked glycosylation (O-GlcNAcylation) on specific proteins in the cumulus-oocyte complex (COC) under hyperglycaemic conditions? 24713123 19 121 contain have 3362:3365 arg1 authors 3354:3360 The other authors 3344:3360 The other authors 3344:3360 The other authors have no conflicts of interest to declare. 24713123 19 121 contain have 3362:3365 arg2 conflicts 3370:3378 no conflicts 3367:3378 no conflicts of interest 3367:3390 The other authors have no conflicts of interest to declare. 24713123 17 122 theme Medical 3216:3222 arg1 Council 3233:3239 Medical Research Council 3216:3239 Medical Research Council 3216:3239 STUDY FUNDING/COMPETING INTEREST(S) This work was supported by a programme grant from the National Health and Medical Research Council, Australia, ID 453556. 24713123 5 123 from levels 1107:1112 arg1 COC 1127:1129 the mouse COC 1117:1129 the mouse COC 1117:1129 STUDY DESIGN, SIZE, DURATION This study was designed to examine the effect of hyperglycaemic conditions (using the hyperglycaemic mimetic, glucosamine) on O-GlcNAc levels in the mouse COC, and furthermore to identify potential candidate proteins which are targets of this modification, and their roles in oocyte maturation. 24713123 2 124 dep conditions 445:454 arg1 modelled 457:464 modelled 457:464 modelled using glucosamine 457:482 SUMMARY ANSWER Heat shock protein 90 (HSP90) was identified and confirmed as being O-GlcNAcylated in mouse COCs under hyperglycaemic conditions (modelled using glucosamine), causing detrimental outcomes for embryo development. 24713123 2 125 theme embryo 519:524 arg1 development 526:536 embryo development 519:536 embryo development 519:536 SUMMARY ANSWER Heat shock protein 90 (HSP90) was identified and confirmed as being O-GlcNAcylated in mouse COCs under hyperglycaemic conditions (modelled using glucosamine), causing detrimental outcomes for embryo development. 24713123 4 126 theme hyperglycaemic 798:811 arg1 conditions 813:822 hyperglycaemic conditions 798:822 hyperglycaemic conditions 798:822 COCs matured under hyperglycaemic conditions have decreased developmental competence, mediated at least in part through the mechanism of increased O-GlcNAcylation. 24713123 0 127 theme protein 127:133 arg1 glycosylation 99:111 beta-O-linked glycosylation 85:111 beta-O-linked glycosylation of heat shock protein 90 85:136 Hyperglycaemic conditions perturb mouse oocyte in vitro developmental competence via beta-O-linked glycosylation of heat shock protein 90. 24713123 13 128 theme prior 2578:2582 arg1 h 2562:2562 the 17 h 2555:2562 the 17 h of maturation prior to ovulation 2555:2595 LIMITATIONS, REASONS FOR CAUTION In vitro maturation of COCs was used so that treatment time could be limited to the 17 h of maturation prior to ovulation. 24713123 15 129 theme hyperglycaemia 2825:2838 arg1 models 2815:2820 in vivo models 2807:2820 in vivo models of hyperglycaemia and different HSP90 inhibitors 2807:2869 The results in this study should be confirmed using in vivo models of hyperglycaemia and different HSP90 inhibitors. 24713123 15 130 from results 2759:2765 arg1 study 2775:2779 this study 2770:2779 this study 2770:2779 The results in this study should be confirmed using in vivo models of hyperglycaemia and different HSP90 inhibitors. 24713123 1 131 link beta-O-linked 176:188 arg1 glycosylation 190:202 beta-O-linked glycosylation 176:202 beta-O-linked glycosylation (O-GlcNAcylation) 176:220 STUDY QUESTION What is the effect of beta-O-linked glycosylation (O-GlcNAcylation) on specific proteins in the cumulus-oocyte complex (COC) under hyperglycaemic conditions? 24713123 1 131 link beta-O-linked 176:188 arg1 O-GlcNAcylation 205:219 O-GlcNAcylation 205:219 O-GlcNAcylation 205:219 STUDY QUESTION What is the effect of beta-O-linked glycosylation (O-GlcNAcylation) on specific proteins in the cumulus-oocyte complex (COC) under hyperglycaemic conditions? 24713123 0 132 theme mouse 34:38 arg1 competence 70:79 mouse oocyte in vitro developmental competence 34:79 mouse oocyte in vitro developmental competence 34:79 Hyperglycaemic conditions perturb mouse oocyte in vitro developmental competence via beta-O-linked glycosylation of heat shock protein 90. 24713123 1 133 theme hyperglycaemic 285:298 arg1 conditions 300:309 hyperglycaemic conditions 285:309 hyperglycaemic conditions 285:309 STUDY QUESTION What is the effect of beta-O-linked glycosylation (O-GlcNAcylation) on specific proteins in the cumulus-oocyte complex (COC) under hyperglycaemic conditions? 24713123 2 134 theme hyperglycaemic 430:443 arg1 conditions 445:454 hyperglycaemic conditions 430:454 hyperglycaemic conditions (modelled using glucosamine) 430:483 SUMMARY ANSWER Heat shock protein 90 (HSP90) was identified and confirmed as being O-GlcNAcylated in mouse COCs under hyperglycaemic conditions (modelled using glucosamine), causing detrimental outcomes for embryo development. 24713123 10 135 theme glucosamine 1917:1927 arg1 Addition 1878:1885 CHANCE Addition 1871:1885 CHANCE Addition of the hyperglycaemic mimetic glucosamine to IVM medium 1871:1941 MAIN RESULTS AND THE ROLE OF CHANCE Addition of the hyperglycaemic mimetic glucosamine to IVM medium for mouse COCs increased detectable O-GlcNAcylated protein levels (by western blot and immunocytochemistry), and this effect was reversed using an OGT inhibitor (P < 0.05). 24713123 0 136 theme in 47:48 arg1 competence 70:79 mouse oocyte in vitro developmental competence 34:79 mouse oocyte in vitro developmental competence 34:79 Hyperglycaemic conditions perturb mouse oocyte in vitro developmental competence via beta-O-linked glycosylation of heat shock protein 90. 24713123 6 137 from mice 1373:1376 arg1 COCs 1308:1311 PARTICIPANTS/MATERIALS, SETTING, METHODS COCs 1267:1311 PARTICIPANTS/MATERIALS, SETTING, METHODS COCs from 21-day-old superovulated CBA × C57BL6 F1 hybrid female mice 1267:1376 PARTICIPANTS/MATERIALS, SETTING, METHODS COCs from 21-day-old superovulated CBA × C57BL6 F1 hybrid female mice were matured in vitro (IVM). 24713123 8 138 gly glycosylated 1622:1633 arg1 levels 1641:1646 glycosylated HSP90 levels 1622:1646 glycosylated HSP90 levels 1622:1646 For glycosylated HSP90 levels, and to test OGT-HSP90 interaction, immunoprecipitation was performed prior to western blotting. 24713123 7 139 from Levels 1407:1412 arg1 COCs 1526:1529 COCs 1526:1529 COCs 1526:1529 Levels of O-GlcNAcylated proteins, HSP90 and O-GlcNAc transferase (OGT, the enzyme responsible for O-GlcNAcylation) in COCs were measured using western blot, and localization observed using immunocytochemistry. 24713123 3 140 theme biosynthesis 648:659 arg1 pathway 661:667 the hexosamine biosynthesis pathway 633:667 the hexosamine biosynthesis pathway 633:667 WHAT IS KNOWN ALREADY O-GlcNAcylation of proteins occurs as a result of increased activity of the hexosamine biosynthesis pathway, which provides substrates for cumulus matrix production during COC maturation, and also for O-GlcNAcylation. 24713123 11 141 theme developmental 2264:2276 arg1 competence 2278:2287 oocyte developmental competence 2257:2287 oocyte developmental competence (P < 0.05) 2257:2298 HSP90 was identified as a target of O-GlcNAcylation in the COC, and inhibition of HSP90 during IVM reversed glucosamine-induced decreases in oocyte developmental competence (P < 0.05). 24713123 11 141 theme developmental 2264:2276 arg1 < 2292:2292 P < 0.05 2290:2297 P < 0.05 2290:2297 HSP90 was identified as a target of O-GlcNAcylation in the COC, and inhibition of HSP90 during IVM reversed glucosamine-induced decreases in oocyte developmental competence (P < 0.05). 24713123 0 142 theme developmental 56:68 arg1 competence 70:79 mouse oocyte in vitro developmental competence 34:79 mouse oocyte in vitro developmental competence 34:79 Hyperglycaemic conditions perturb mouse oocyte in vitro developmental competence via beta-O-linked glycosylation of heat shock protein 90. 24713123 0 143 dep in 47:48 arg1 vitro 50:54 vitro 50:54 vitro 50:54 Hyperglycaemic conditions perturb mouse oocyte in vitro developmental competence via beta-O-linked glycosylation of heat shock protein 90. 24713123 0 144 link beta-O-linked 85:97 arg1 glycosylation 99:111 beta-O-linked glycosylation 85:111 beta-O-linked glycosylation of heat shock protein 90 85:136 Hyperglycaemic conditions perturb mouse oocyte in vitro developmental competence via beta-O-linked glycosylation of heat shock protein 90. 24713123 14 145 theme hexosamine 2698:2707 arg1 pathway 2709:2715 the hexosamine pathway 2694:2715 the hexosamine pathway which provides the O-GlcNAc moieties 2694:2752 Additionally, glucosamine, a hyperglycaemic mimetic, was used because it specifically activates the hexosamine pathway which provides the O-GlcNAc moieties. 24713123 11 146 theme HSP90 2198:2202 arg1 inhibition 2184:2193 inhibition 2184:2193 inhibition of HSP90 during IVM 2184:2213 HSP90 was identified as a target of O-GlcNAcylation in the COC, and inhibition of HSP90 during IVM reversed glucosamine-induced decreases in oocyte developmental competence (P < 0.05). 24713123 19 147 theme interest 3383:3390 arg1 conflicts 3370:3378 no conflicts 3367:3378 no conflicts of interest 3367:3390 The other authors have no conflicts of interest to declare. 24713123 5 148 theme hyperglycaemic 1021:1034 arg1 conditions 1036:1045 hyperglycaemic conditions 1021:1045 hyperglycaemic conditions (using the hyperglycaemic mimetic, glucosamine) 1021:1093 STUDY DESIGN, SIZE, DURATION This study was designed to examine the effect of hyperglycaemic conditions (using the hyperglycaemic mimetic, glucosamine) on O-GlcNAc levels in the mouse COC, and furthermore to identify potential candidate proteins which are targets of this modification, and their roles in oocyte maturation. 24713123 8 149 theme HSP90 1635:1639 arg1 levels 1641:1646 glycosylated HSP90 levels 1622:1646 glycosylated HSP90 levels 1622:1646 For glycosylated HSP90 levels, and to test OGT-HSP90 interaction, immunoprecipitation was performed prior to western blotting. 24713123 10 150 theme IVM 1932:1934 arg1 medium 1936:1941 IVM medium 1932:1941 IVM medium 1932:1941 MAIN RESULTS AND THE ROLE OF CHANCE Addition of the hyperglycaemic mimetic glucosamine to IVM medium for mouse COCs increased detectable O-GlcNAcylated protein levels (by western blot and immunocytochemistry), and this effect was reversed using an OGT inhibitor (P < 0.05). 24713123 12 151 theme possible 2402:2409 arg1 relationship 2428:2439 a possible client-chaperone relationship 2400:2439 a possible client-chaperone relationship 2400:2439 We also demonstrated the novel finding of an association between HSP90 and OGT in COCs, suggesting a possible client-chaperone relationship. 24713123 10 152 theme detectable 1968:1977 arg1 levels 2002:2007 detectable O-GlcNAcylated protein levels 1968:2007 detectable O-GlcNAcylated protein levels 1968:2007 MAIN RESULTS AND THE ROLE OF CHANCE Addition of the hyperglycaemic mimetic glucosamine to IVM medium for mouse COCs increased detectable O-GlcNAcylated protein levels (by western blot and immunocytochemistry), and this effect was reversed using an OGT inhibitor (P < 0.05). 24713123 4 153 theme developmental 839:851 arg1 competence 853:862 decreased developmental competence 829:862 decreased developmental competence 829:862 COCs matured under hyperglycaemic conditions have decreased developmental competence, mediated at least in part through the mechanism of increased O-GlcNAcylation. 24713123 5 154 from effect 1011:1016 arg1 levels 1107:1112 O-GlcNAc levels 1098:1112 O-GlcNAc levels in the mouse COC 1098:1129 STUDY DESIGN, SIZE, DURATION This study was designed to examine the effect of hyperglycaemic conditions (using the hyperglycaemic mimetic, glucosamine) on O-GlcNAc levels in the mouse COC, and furthermore to identify potential candidate proteins which are targets of this modification, and their roles in oocyte maturation. 24713123 1 155 theme cumulus-oocyte 250:263 arg1 COC 274:276 COC 274:276 COC 274:276 STUDY QUESTION What is the effect of beta-O-linked glycosylation (O-GlcNAcylation) on specific proteins in the cumulus-oocyte complex (COC) under hyperglycaemic conditions? 24713123 1 155 theme cumulus-oocyte 250:263 arg1 complex 265:271 cumulus-oocyte complex 250:271 the cumulus-oocyte complex (COC) 246:277 STUDY QUESTION What is the effect of beta-O-linked glycosylation (O-GlcNAcylation) on specific proteins in the cumulus-oocyte complex (COC) under hyperglycaemic conditions? 24809953 4 0 from fluoroquinolones 614:629 arg1 distinct 596:603 distinct 596:603 distinct 596:603 The mechanism of inhibition of DNA gyrase was distinct from the fluoroquinolones, as shown by their ability to inhibit the growth of fluoroquinolone-resistant Mtb. 24809953 4 0 from fluoroquinolones 614:629 arg1 mechanism 554:562 The mechanism 550:562 The mechanism of inhibition of DNA gyrase 550:590 The mechanism of inhibition of DNA gyrase was distinct from the fluoroquinolones, as shown by their ability to inhibit the growth of fluoroquinolone-resistant Mtb. 24809953 5 1 theme single-strand 782:794 arg1 cleavage 796:803 single-strand cleavage 782:803 single-strand cleavage rather than double-strand cleavage 782:838 Biochemical studies demonstrated this class to exert its action via single-strand cleavage rather than double-strand cleavage, as seen with fluoroquinolones. 24809953 7 2 theme improved 1036:1043 arg1 bioavailability 1050:1064 improved oral bioavailability 1036:1064 improved oral bioavailability 1036:1064 Lead optimization resulted in the identification of potent compounds with improved oral bioavailability and reduced cardiac ion channel liability. 24809953 7 3 theme potent 1014:1019 arg1 compounds 1021:1029 potent compounds 1014:1029 potent compounds with improved oral bioavailability and reduced cardiac ion channel liability 1014:1106 Lead optimization resulted in the identification of potent compounds with improved oral bioavailability and reduced cardiac ion channel liability. 24809953 4 4 theme Mtb 709:711 arg1 growth 673:678 the growth 669:678 the growth of fluoroquinolone-resistant Mtb 669:711 The mechanism of inhibition of DNA gyrase was distinct from the fluoroquinolones, as shown by their ability to inhibit the growth of fluoroquinolone-resistant Mtb. 24809953 4 5 theme gyrase 585:590 arg1 inhibition 567:576 inhibition 567:576 inhibition of DNA gyrase 567:590 The mechanism of inhibition of DNA gyrase was distinct from the fluoroquinolones, as shown by their ability to inhibit the growth of fluoroquinolone-resistant Mtb. 24809953 0 6 theme Mycobacterium 103:115 arg1 tuberculosis 117:128 Mycobacterium tuberculosis 103:128 Mycobacterium tuberculosis 103:128 Novel N-linked aminopiperidine-based gyrase inhibitors with improved hERG and in vivo efficacy against Mycobacterium tuberculosis. 24809953 6 7 theme intracellular 943:955 arg1 Mtb 957:959 intracellular Mtb 943:959 extracellular as well as intracellular Mtb 918:959 The compounds are highly bactericidal against extracellular as well as intracellular Mtb. 24809953 7 8 theme compounds 1021:1029 arg1 identification 996:1009 the identification 992:1009 the identification of potent compounds with improved oral bioavailability and reduced cardiac ion channel liability 992:1106 Lead optimization resulted in the identification of potent compounds with improved oral bioavailability and reduced cardiac ion channel liability. 24809953 0 9 link N-linked 6:13 arg1 efficacy 86:93 in vivo efficacy 78:93 in vivo efficacy against Mycobacterium tuberculosis 78:128 Novel N-linked aminopiperidine-based gyrase inhibitors with improved hERG and in vivo efficacy against Mycobacterium tuberculosis. 24809953 0 9 link N-linked 6:13 arg1 inhibitors 44:53 Novel N-linked aminopiperidine-based gyrase inhibitors 0:53 Novel N-linked aminopiperidine-based gyrase inhibitors 0:53 Novel N-linked aminopiperidine-based gyrase inhibitors with improved hERG and in vivo efficacy against Mycobacterium tuberculosis. 24809953 0 9 link N-linked 6:13 arg1 hERG 69:72 improved hERG 60:72 improved hERG 60:72 Novel N-linked aminopiperidine-based gyrase inhibitors with improved hERG and in vivo efficacy against Mycobacterium tuberculosis. 24809953 2 10 theme anti-tuberculosis 287:303 arg1 drugs 305:309 anti-tuberculosis drugs 287:309 anti-tuberculosis drugs 287:309 Despite the promise of fluoroquinolones (FQs) as anti-tuberculosis drugs, the prevalence of pre-existing resistance to FQs is likely to restrict their clinical value. 24809953 8 11 from models 1170:1175 arg1 efficacious 1140:1150 efficacious 1140:1150 efficacious 1140:1150 Compounds from this series are efficacious in various murine models of tuberculosis. 24809953 7 12 dep Lead 962:965 arg1 resulted 980:987 resulted 980:987 resulted in the identification of potent compounds with improved oral bioavailability and reduced cardiac ion channel liability 980:1106 Lead optimization resulted in the identification of potent compounds with improved oral bioavailability and reduced cardiac ion channel liability. 24809953 3 13 theme N-linked 434:441 arg1 quinolones 466:475 N-linked aminopiperidinyl alkyl quinolones 434:475 N-linked aminopiperidinyl alkyl quinolones 434:475 We describe a novel class of N-linked aminopiperidinyl alkyl quinolones and naphthyridones that kills Mtb by inhibiting the DNA gyrase activity. 24809953 3 14 theme aminopiperidinyl 443:458 arg1 quinolones 466:475 N-linked aminopiperidinyl alkyl quinolones 434:475 N-linked aminopiperidinyl alkyl quinolones 434:475 We describe a novel class of N-linked aminopiperidinyl alkyl quinolones and naphthyridones that kills Mtb by inhibiting the DNA gyrase activity. 24809953 0 15 theme N-linked 6:13 arg1 efficacy 86:93 in vivo efficacy 78:93 in vivo efficacy against Mycobacterium tuberculosis 78:128 Novel N-linked aminopiperidine-based gyrase inhibitors with improved hERG and in vivo efficacy against Mycobacterium tuberculosis. 24809953 0 15 theme N-linked 6:13 arg1 inhibitors 44:53 Novel N-linked aminopiperidine-based gyrase inhibitors 0:53 Novel N-linked aminopiperidine-based gyrase inhibitors 0:53 Novel N-linked aminopiperidine-based gyrase inhibitors with improved hERG and in vivo efficacy against Mycobacterium tuberculosis. 24809953 0 15 theme N-linked 6:13 arg1 hERG 69:72 improved hERG 60:72 improved hERG 60:72 Novel N-linked aminopiperidine-based gyrase inhibitors with improved hERG and in vivo efficacy against Mycobacterium tuberculosis. 24809953 3 16 link N-linked 434:441 arg1 quinolones 466:475 N-linked aminopiperidinyl alkyl quinolones 434:475 N-linked aminopiperidinyl alkyl quinolones 434:475 We describe a novel class of N-linked aminopiperidinyl alkyl quinolones and naphthyridones that kills Mtb by inhibiting the DNA gyrase activity. 24809953 2 17 theme clinical 389:396 arg1 value 398:402 their clinical value 383:402 their clinical value 383:402 Despite the promise of fluoroquinolones (FQs) as anti-tuberculosis drugs, the prevalence of pre-existing resistance to FQs is likely to restrict their clinical value. 24809953 0 18 theme Novel 0:4 arg1 efficacy 86:93 in vivo efficacy 78:93 in vivo efficacy against Mycobacterium tuberculosis 78:128 Novel N-linked aminopiperidine-based gyrase inhibitors with improved hERG and in vivo efficacy against Mycobacterium tuberculosis. 24809953 0 18 theme Novel 0:4 arg1 inhibitors 44:53 Novel N-linked aminopiperidine-based gyrase inhibitors 0:53 Novel N-linked aminopiperidine-based gyrase inhibitors 0:53 Novel N-linked aminopiperidine-based gyrase inhibitors with improved hERG and in vivo efficacy against Mycobacterium tuberculosis. 24809953 0 18 theme Novel 0:4 arg1 hERG 69:72 improved hERG 60:72 improved hERG 60:72 Novel N-linked aminopiperidine-based gyrase inhibitors with improved hERG and in vivo efficacy against Mycobacterium tuberculosis. 24809953 4 19 theme inhibition 567:576 arg1 distinct 596:603 distinct 596:603 distinct 596:603 The mechanism of inhibition of DNA gyrase was distinct from the fluoroquinolones, as shown by their ability to inhibit the growth of fluoroquinolone-resistant Mtb. 24809953 4 19 theme inhibition 567:576 arg1 mechanism 554:562 The mechanism 550:562 The mechanism of inhibition of DNA gyrase 550:590 The mechanism of inhibition of DNA gyrase was distinct from the fluoroquinolones, as shown by their ability to inhibit the growth of fluoroquinolone-resistant Mtb. 24809953 1 20 theme Mycobacterium 204:216 arg1 Mtb 232:234 Mtb 232:234 Mtb 232:234 DNA gyrase is a clinically validated target for developing drugs against Mycobacterium tuberculosis (Mtb). 24809953 1 20 theme Mycobacterium 204:216 arg1 tuberculosis 218:229 Mycobacterium tuberculosis 204:229 Mycobacterium tuberculosis (Mtb) 204:235 DNA gyrase is a clinically validated target for developing drugs against Mycobacterium tuberculosis (Mtb). 24809953 0 21 theme gyrase 37:42 arg1 efficacy 86:93 in vivo efficacy 78:93 in vivo efficacy against Mycobacterium tuberculosis 78:128 Novel N-linked aminopiperidine-based gyrase inhibitors with improved hERG and in vivo efficacy against Mycobacterium tuberculosis. 24809953 0 21 theme gyrase 37:42 arg1 inhibitors 44:53 Novel N-linked aminopiperidine-based gyrase inhibitors 0:53 Novel N-linked aminopiperidine-based gyrase inhibitors 0:53 Novel N-linked aminopiperidine-based gyrase inhibitors with improved hERG and in vivo efficacy against Mycobacterium tuberculosis. 24809953 0 21 theme gyrase 37:42 arg1 hERG 69:72 improved hERG 60:72 improved hERG 60:72 Novel N-linked aminopiperidine-based gyrase inhibitors with improved hERG and in vivo efficacy against Mycobacterium tuberculosis. 24809953 5 22 theme Biochemical 714:724 arg1 studies 726:732 Biochemical studies 714:732 Biochemical studies 714:732 Biochemical studies demonstrated this class to exert its action via single-strand cleavage rather than double-strand cleavage, as seen with fluoroquinolones. 24809953 0 23 dep inhibitors 44:53 arg1 efficacy 86:93 in vivo efficacy 78:93 in vivo efficacy against Mycobacterium tuberculosis 78:128 Novel N-linked aminopiperidine-based gyrase inhibitors with improved hERG and in vivo efficacy against Mycobacterium tuberculosis. 24809953 0 23 dep inhibitors 44:53 arg1 inhibitors 44:53 Novel N-linked aminopiperidine-based gyrase inhibitors 0:53 Novel N-linked aminopiperidine-based gyrase inhibitors 0:53 Novel N-linked aminopiperidine-based gyrase inhibitors with improved hERG and in vivo efficacy against Mycobacterium tuberculosis. 24809953 0 23 dep inhibitors 44:53 arg1 hERG 69:72 improved hERG 60:72 improved hERG 60:72 Novel N-linked aminopiperidine-based gyrase inhibitors with improved hERG and in vivo efficacy against Mycobacterium tuberculosis. 24809953 0 24 dep in 78:79 arg1 vivo 81:84 vivo 81:84 vivo 81:84 Novel N-linked aminopiperidine-based gyrase inhibitors with improved hERG and in vivo efficacy against Mycobacterium tuberculosis. 24809953 0 25 theme aminopiperidine-based 15:35 arg1 efficacy 86:93 in vivo efficacy 78:93 in vivo efficacy against Mycobacterium tuberculosis 78:128 Novel N-linked aminopiperidine-based gyrase inhibitors with improved hERG and in vivo efficacy against Mycobacterium tuberculosis. 24809953 0 25 theme aminopiperidine-based 15:35 arg1 inhibitors 44:53 Novel N-linked aminopiperidine-based gyrase inhibitors 0:53 Novel N-linked aminopiperidine-based gyrase inhibitors 0:53 Novel N-linked aminopiperidine-based gyrase inhibitors with improved hERG and in vivo efficacy against Mycobacterium tuberculosis. 24809953 0 25 theme aminopiperidine-based 15:35 arg1 hERG 69:72 improved hERG 60:72 improved hERG 60:72 Novel N-linked aminopiperidine-based gyrase inhibitors with improved hERG and in vivo efficacy against Mycobacterium tuberculosis. 24809953 4 26 theme DNA 581:583 arg1 gyrase 585:590 DNA gyrase 581:590 DNA gyrase 581:590 The mechanism of inhibition of DNA gyrase was distinct from the fluoroquinolones, as shown by their ability to inhibit the growth of fluoroquinolone-resistant Mtb. 24809953 4 27 theme fluoroquinolone-resistant 683:707 arg1 Mtb 709:711 fluoroquinolone-resistant Mtb 683:711 fluoroquinolone-resistant Mtb 683:711 The mechanism of inhibition of DNA gyrase was distinct from the fluoroquinolones, as shown by their ability to inhibit the growth of fluoroquinolone-resistant Mtb. 24809953 8 28 theme murine 1163:1168 arg1 models 1170:1175 various murine models 1155:1175 various murine models of tuberculosis 1155:1191 Compounds from this series are efficacious in various murine models of tuberculosis. 24809953 3 29 theme alkyl 460:464 arg1 quinolones 466:475 N-linked aminopiperidinyl alkyl quinolones 434:475 N-linked aminopiperidinyl alkyl quinolones 434:475 We describe a novel class of N-linked aminopiperidinyl alkyl quinolones and naphthyridones that kills Mtb by inhibiting the DNA gyrase activity. 24809953 3 30 theme novel 419:423 arg1 class 425:429 a novel class 417:429 a novel class of N-linked aminopiperidinyl alkyl quinolones 417:475 We describe a novel class of N-linked aminopiperidinyl alkyl quinolones and naphthyridones that kills Mtb by inhibiting the DNA gyrase activity. 24809953 8 31 theme various 1155:1161 arg1 models 1170:1175 various murine models 1155:1175 various murine models of tuberculosis 1155:1191 Compounds from this series are efficacious in various murine models of tuberculosis. 24809953 7 32 theme cardiac 1078:1084 arg1 liability 1098:1106 reduced cardiac ion channel liability 1070:1106 reduced cardiac ion channel liability 1070:1106 Lead optimization resulted in the identification of potent compounds with improved oral bioavailability and reduced cardiac ion channel liability. 24809953 3 33 theme quinolones 466:475 arg1 class 425:429 a novel class 417:429 a novel class of N-linked aminopiperidinyl alkyl quinolones 417:475 We describe a novel class of N-linked aminopiperidinyl alkyl quinolones and naphthyridones that kills Mtb by inhibiting the DNA gyrase activity. 24809953 5 34 theme double-strand 817:829 arg1 cleavage 831:838 double-strand cleavage 817:838 single-strand cleavage rather than double-strand cleavage 782:838 Biochemical studies demonstrated this class to exert its action via single-strand cleavage rather than double-strand cleavage, as seen with fluoroquinolones. 24809953 8 35 from series 1129:1134 arg1 Compounds 1109:1117 Compounds 1109:1117 Compounds from this series 1109:1134 Compounds from this series are efficacious in various murine models of tuberculosis. 24809953 7 36 theme ion 1086:1088 arg1 liability 1098:1106 reduced cardiac ion channel liability 1070:1106 reduced cardiac ion channel liability 1070:1106 Lead optimization resulted in the identification of potent compounds with improved oral bioavailability and reduced cardiac ion channel liability. 24809953 1 37 theme DNA 131:133 arg1 target 168:173 a clinically validated target 145:173 a clinically validated target for developing drugs against Mycobacterium tuberculosis (Mtb) 145:235 DNA gyrase is a clinically validated target for developing drugs against Mycobacterium tuberculosis (Mtb). 24809953 1 37 theme DNA 131:133 arg1 gyrase 135:140 DNA gyrase 131:140 DNA gyrase 131:140 DNA gyrase is a clinically validated target for developing drugs against Mycobacterium tuberculosis (Mtb). 24809953 0 38 theme improved 60:67 arg1 inhibitors 44:53 Novel N-linked aminopiperidine-based gyrase inhibitors 0:53 Novel N-linked aminopiperidine-based gyrase inhibitors 0:53 Novel N-linked aminopiperidine-based gyrase inhibitors with improved hERG and in vivo efficacy against Mycobacterium tuberculosis. 24809953 0 38 theme improved 60:67 arg1 hERG 69:72 improved hERG 60:72 improved hERG 60:72 Novel N-linked aminopiperidine-based gyrase inhibitors with improved hERG and in vivo efficacy against Mycobacterium tuberculosis. 24809953 1 39 theme validated 158:166 arg1 target 168:173 a clinically validated target 145:173 a clinically validated target for developing drugs against Mycobacterium tuberculosis (Mtb) 145:235 DNA gyrase is a clinically validated target for developing drugs against Mycobacterium tuberculosis (Mtb). 24809953 1 39 theme validated 158:166 arg1 gyrase 135:140 DNA gyrase 131:140 DNA gyrase 131:140 DNA gyrase is a clinically validated target for developing drugs against Mycobacterium tuberculosis (Mtb). 24809953 7 40 with compounds 1021:1029 arg1 bioavailability 1050:1064 improved oral bioavailability 1036:1064 improved oral bioavailability 1036:1064 Lead optimization resulted in the identification of potent compounds with improved oral bioavailability and reduced cardiac ion channel liability. 24809953 7 40 with compounds 1021:1029 arg1 liability 1098:1106 reduced cardiac ion channel liability 1070:1106 reduced cardiac ion channel liability 1070:1106 Lead optimization resulted in the identification of potent compounds with improved oral bioavailability and reduced cardiac ion channel liability. 24809953 7 41 theme channel 1090:1096 arg1 liability 1098:1106 reduced cardiac ion channel liability 1070:1106 reduced cardiac ion channel liability 1070:1106 Lead optimization resulted in the identification of potent compounds with improved oral bioavailability and reduced cardiac ion channel liability. 24809953 7 42 theme reduced 1070:1076 arg1 liability 1098:1106 reduced cardiac ion channel liability 1070:1106 reduced cardiac ion channel liability 1070:1106 Lead optimization resulted in the identification of potent compounds with improved oral bioavailability and reduced cardiac ion channel liability. 24809953 2 43 theme resistance 343:352 arg1 likely 364:369 likely 364:369 likely 364:369 Despite the promise of fluoroquinolones (FQs) as anti-tuberculosis drugs, the prevalence of pre-existing resistance to FQs is likely to restrict their clinical value. 24809953 2 43 theme resistance 343:352 arg1 prevalence 316:325 the prevalence 312:325 the prevalence of pre-existing resistance to FQs 312:359 Despite the promise of fluoroquinolones (FQs) as anti-tuberculosis drugs, the prevalence of pre-existing resistance to FQs is likely to restrict their clinical value. 24809953 8 44 theme tuberculosis 1180:1191 arg1 models 1170:1175 various murine models 1155:1175 various murine models of tuberculosis 1155:1191 Compounds from this series are efficacious in various murine models of tuberculosis. 24809953 7 45 theme oral 1045:1048 arg1 bioavailability 1050:1064 improved oral bioavailability 1036:1064 improved oral bioavailability 1036:1064 Lead optimization resulted in the identification of potent compounds with improved oral bioavailability and reduced cardiac ion channel liability. 24809953 2 46 theme pre-existing 330:341 arg1 resistance 343:352 pre-existing resistance 330:352 pre-existing resistance to FQs 330:359 Despite the promise of fluoroquinolones (FQs) as anti-tuberculosis drugs, the prevalence of pre-existing resistance to FQs is likely to restrict their clinical value. 24809953 0 47 theme in 78:79 arg1 efficacy 86:93 in vivo efficacy 78:93 in vivo efficacy against Mycobacterium tuberculosis 78:128 Novel N-linked aminopiperidine-based gyrase inhibitors with improved hERG and in vivo efficacy against Mycobacterium tuberculosis. 24809953 0 47 theme in 78:79 arg1 inhibitors 44:53 Novel N-linked aminopiperidine-based gyrase inhibitors 0:53 Novel N-linked aminopiperidine-based gyrase inhibitors 0:53 Novel N-linked aminopiperidine-based gyrase inhibitors with improved hERG and in vivo efficacy against Mycobacterium tuberculosis. 24809953 2 48 theme fluoroquinolones 261:276 arg1 promise 250:256 the promise 246:256 the promise of fluoroquinolones (FQs) as anti-tuberculosis drugs 246:309 Despite the promise of fluoroquinolones (FQs) as anti-tuberculosis drugs, the prevalence of pre-existing resistance to FQs is likely to restrict their clinical value. 24809953 3 49 theme DNA 529:531 arg1 activity 540:547 the DNA gyrase activity 525:547 the DNA gyrase activity 525:547 We describe a novel class of N-linked aminopiperidinyl alkyl quinolones and naphthyridones that kills Mtb by inhibiting the DNA gyrase activity. 24809953 3 50 theme gyrase 533:538 arg1 activity 540:547 the DNA gyrase activity 525:547 the DNA gyrase activity 525:547 We describe a novel class of N-linked aminopiperidinyl alkyl quinolones and naphthyridones that kills Mtb by inhibiting the DNA gyrase activity. 24809953 8 51 from efficacious 1140:1150 arg1 models 1170:1175 various murine models 1155:1175 various murine models of tuberculosis 1155:1191 Compounds from this series are efficacious in various murine models of tuberculosis. 24434114 0 0 theme scaffold 91:98 arg1 hopping 100:106 scaffold hopping 91:106 Development of novel N-linked aminopiperidine-based mycobacterial DNA gyrase B inhibitors: scaffold hopping from known antibacterial leads. 0:138 Development of novel N-linked aminopiperidine-based mycobacterial DNA gyrase B inhibitors: scaffold hopping from known antibacterial leads. 24434114 2 1 theme mycobacterial 475:487 arg1 domain 496:501 the mycobacterial ATPase domain 471:501 the mycobacterial ATPase domain 471:501 We present the discovery and optimisation of a novel series of mycobacterial DNA gyrase inhibitors with a high degree of specificity towards the mycobacterial ATPase domain. 24434114 3 2 theme μM 875:876 arg1 inhibition 651:660 inhibition 651:660 inhibition of MTB DNA gyrase supercoiling assay with an IC50 (50% inhibitory concentration) of 3.6 ± 0.16 μM 651:758 Compound 5-fluoro-1-(2-(4-(4-(trifluoromethyl)benzylamino)piperidin-1-yl)ethyl)indoline-2,3-dione (17) emerged as the most potent lead, exhibiting inhibition of MTB DNA gyrase supercoiling assay with an IC50 (50% inhibitory concentration) of 3.6 ± 0.16 μM, a Mycobacterium smegmatis GyrB IC50 of 10.6 ± 0.6 μM, and MTB minimum inhibitory concentrations of 6.95 μM and 10 μM against drug-sensitive (MTB H37Rv) and extensively drug-resistant strains, respectively. 24434114 3 2 theme μM 875:876 arg1 IC50 792:795 a Mycobacterium smegmatis GyrB IC50 761:795 a Mycobacterium smegmatis GyrB IC50 of 10.6 ± 0.6 μM 761:812 Compound 5-fluoro-1-(2-(4-(4-(trifluoromethyl)benzylamino)piperidin-1-yl)ethyl)indoline-2,3-dione (17) emerged as the most potent lead, exhibiting inhibition of MTB DNA gyrase supercoiling assay with an IC50 (50% inhibitory concentration) of 3.6 ± 0.16 μM, a Mycobacterium smegmatis GyrB IC50 of 10.6 ± 0.6 μM, and MTB minimum inhibitory concentrations of 6.95 μM and 10 μM against drug-sensitive (MTB H37Rv) and extensively drug-resistant strains, respectively. 24434114 3 2 theme μM 875:876 arg1 concentrations 842:855 MTB minimum inhibitory concentrations 819:855 MTB minimum inhibitory concentrations of 6.95 μM and 10 μM against drug-sensitive (MTB H37Rv) and extensively drug-resistant strains, respectively 819:964 Compound 5-fluoro-1-(2-(4-(4-(trifluoromethyl)benzylamino)piperidin-1-yl)ethyl)indoline-2,3-dione (17) emerged as the most potent lead, exhibiting inhibition of MTB DNA gyrase supercoiling assay with an IC50 (50% inhibitory concentration) of 3.6 ± 0.16 μM, a Mycobacterium smegmatis GyrB IC50 of 10.6 ± 0.6 μM, and MTB minimum inhibitory concentrations of 6.95 μM and 10 μM against drug-sensitive (MTB H37Rv) and extensively drug-resistant strains, respectively. 24434114 1 3 theme tuberculosis 168:179 arg1 target 322:327 a bactericidal drug target 302:327 a bactericidal drug target 302:327 DNA gyrase of Mycobacterium tuberculosis (MTB) is a type II topoisomerase that ensures the regulation of DNA topology and has been genetically demonstrated to be a bactericidal drug target. 24434114 1 3 theme tuberculosis 168:179 arg1 gyrase 144:149 DNA gyrase 140:149 DNA gyrase of Mycobacterium tuberculosis (MTB) 140:185 DNA gyrase of Mycobacterium tuberculosis (MTB) is a type II topoisomerase that ensures the regulation of DNA topology and has been genetically demonstrated to be a bactericidal drug target. 24434114 1 3 theme tuberculosis 168:179 arg1 topoisomerase 200:212 a type II topoisomerase 190:212 a type II topoisomerase that ensures the regulation of DNA topology and has been genetically demonstrated to be a bactericidal drug target 190:327 DNA gyrase of Mycobacterium tuberculosis (MTB) is a type II topoisomerase that ensures the regulation of DNA topology and has been genetically demonstrated to be a bactericidal drug target. 24434114 3 4 theme ± 805:805 arg1 μM 811:812 10.6 ± 0.6 μM 800:812 10.6 ± 0.6 μM 800:812 Compound 5-fluoro-1-(2-(4-(4-(trifluoromethyl)benzylamino)piperidin-1-yl)ethyl)indoline-2,3-dione (17) emerged as the most potent lead, exhibiting inhibition of MTB DNA gyrase supercoiling assay with an IC50 (50% inhibitory concentration) of 3.6 ± 0.16 μM, a Mycobacterium smegmatis GyrB IC50 of 10.6 ± 0.6 μM, and MTB minimum inhibitory concentrations of 6.95 μM and 10 μM against drug-sensitive (MTB H37Rv) and extensively drug-resistant strains, respectively. 24434114 1 5 theme DNA 245:247 arg1 topology 249:256 DNA topology 245:256 DNA topology 245:256 DNA gyrase of Mycobacterium tuberculosis (MTB) is a type II topoisomerase that ensures the regulation of DNA topology and has been genetically demonstrated to be a bactericidal drug target. 24434114 0 6 link N-linked 21:28 arg1 inhibitors 79:88 novel N-linked aminopiperidine-based mycobacterial DNA gyrase B inhibitors 15:88 novel N-linked aminopiperidine-based mycobacterial DNA gyrase B inhibitors 15:88 Development of novel N-linked aminopiperidine-based mycobacterial DNA gyrase B inhibitors: scaffold hopping from known antibacterial leads. 24434114 3 7 theme Compound 504:511 arg1 5-fluoro-1- 513:523 Compound 5-fluoro-1- 504:523 Compound 5-fluoro-1-(2-(4-(4-(trifluoromethyl)benzylamino)piperidin-1-yl)ethyl)indoline-2,3-dione (17) 504:605 Compound 5-fluoro-1-(2-(4-(4-(trifluoromethyl)benzylamino)piperidin-1-yl)ethyl)indoline-2,3-dione (17) emerged as the most potent lead, exhibiting inhibition of MTB DNA gyrase supercoiling assay with an IC50 (50% inhibitory concentration) of 3.6 ± 0.16 μM, a Mycobacterium smegmatis GyrB IC50 of 10.6 ± 0.6 μM, and MTB minimum inhibitory concentrations of 6.95 μM and 10 μM against drug-sensitive (MTB H37Rv) and extensively drug-resistant strains, respectively. 24434114 3 7 theme Compound 504:511 arg1 ethyl 577:581 2-(4-(4-(trifluoromethyl)benzylamino)piperidin-1-yl)ethyl 525:581 2-(4-(4-(trifluoromethyl)benzylamino)piperidin-1-yl)ethyl 525:581 Compound 5-fluoro-1-(2-(4-(4-(trifluoromethyl)benzylamino)piperidin-1-yl)ethyl)indoline-2,3-dione (17) emerged as the most potent lead, exhibiting inhibition of MTB DNA gyrase supercoiling assay with an IC50 (50% inhibitory concentration) of 3.6 ± 0.16 μM, a Mycobacterium smegmatis GyrB IC50 of 10.6 ± 0.6 μM, and MTB minimum inhibitory concentrations of 6.95 μM and 10 μM against drug-sensitive (MTB H37Rv) and extensively drug-resistant strains, respectively. 24434114 1 8 theme topology 249:256 arg1 regulation 231:240 the regulation 227:240 the regulation of DNA topology 227:256 DNA gyrase of Mycobacterium tuberculosis (MTB) is a type II topoisomerase that ensures the regulation of DNA topology and has been genetically demonstrated to be a bactericidal drug target. 24434114 4 9 theme ether-à-go-go-related 1048:1068 arg1 zERG 1076:1079 zERG 1076:1079 zERG 1076:1079 Furthermore, the compounds did not show any signs of cardiotoxicity in zebrafish ether-à-go-go-related gene (zERG), and hence constitute a major breakthrough among the otherwise cardiotoxic N-linked aminopiperidine analogues. 24434114 4 9 theme ether-à-go-go-related 1048:1068 arg1 gene 1070:1073 zebrafish ether-à-go-go-related gene 1038:1073 zebrafish ether-à-go-go-related gene (zERG) 1038:1080 Furthermore, the compounds did not show any signs of cardiotoxicity in zebrafish ether-à-go-go-related gene (zERG), and hence constitute a major breakthrough among the otherwise cardiotoxic N-linked aminopiperidine analogues. 24434114 4 10 theme cardiotoxic 1145:1155 arg1 analogues 1182:1190 the otherwise cardiotoxic N-linked aminopiperidine analogues 1131:1190 the otherwise cardiotoxic N-linked aminopiperidine analogues 1131:1190 Furthermore, the compounds did not show any signs of cardiotoxicity in zebrafish ether-à-go-go-related gene (zERG), and hence constitute a major breakthrough among the otherwise cardiotoxic N-linked aminopiperidine analogues. 24434114 0 11 dep antibacterial 119:131 arg1 leads 133:137 leads 133:137 leads 133:137 Development of novel N-linked aminopiperidine-based mycobacterial DNA gyrase B inhibitors: scaffold hopping from known antibacterial leads. 24434114 4 12 theme major 1106:1110 arg1 breakthrough 1112:1123 a major breakthrough 1104:1123 a major breakthrough among the otherwise cardiotoxic N-linked aminopiperidine analogues 1104:1190 Furthermore, the compounds did not show any signs of cardiotoxicity in zebrafish ether-à-go-go-related gene (zERG), and hence constitute a major breakthrough among the otherwise cardiotoxic N-linked aminopiperidine analogues. 24434114 3 13 theme gyrase 673:678 arg1 inhibition 651:660 inhibition 651:660 inhibition of MTB DNA gyrase supercoiling assay with an IC50 (50% inhibitory concentration) of 3.6 ± 0.16 μM 651:758 Compound 5-fluoro-1-(2-(4-(4-(trifluoromethyl)benzylamino)piperidin-1-yl)ethyl)indoline-2,3-dione (17) emerged as the most potent lead, exhibiting inhibition of MTB DNA gyrase supercoiling assay with an IC50 (50% inhibitory concentration) of 3.6 ± 0.16 μM, a Mycobacterium smegmatis GyrB IC50 of 10.6 ± 0.6 μM, and MTB minimum inhibitory concentrations of 6.95 μM and 10 μM against drug-sensitive (MTB H37Rv) and extensively drug-resistant strains, respectively. 24434114 3 13 theme gyrase 673:678 arg1 IC50 792:795 a Mycobacterium smegmatis GyrB IC50 761:795 a Mycobacterium smegmatis GyrB IC50 of 10.6 ± 0.6 μM 761:812 Compound 5-fluoro-1-(2-(4-(4-(trifluoromethyl)benzylamino)piperidin-1-yl)ethyl)indoline-2,3-dione (17) emerged as the most potent lead, exhibiting inhibition of MTB DNA gyrase supercoiling assay with an IC50 (50% inhibitory concentration) of 3.6 ± 0.16 μM, a Mycobacterium smegmatis GyrB IC50 of 10.6 ± 0.6 μM, and MTB minimum inhibitory concentrations of 6.95 μM and 10 μM against drug-sensitive (MTB H37Rv) and extensively drug-resistant strains, respectively. 24434114 3 13 theme gyrase 673:678 arg1 concentrations 842:855 MTB minimum inhibitory concentrations 819:855 MTB minimum inhibitory concentrations of 6.95 μM and 10 μM against drug-sensitive (MTB H37Rv) and extensively drug-resistant strains, respectively 819:964 Compound 5-fluoro-1-(2-(4-(4-(trifluoromethyl)benzylamino)piperidin-1-yl)ethyl)indoline-2,3-dione (17) emerged as the most potent lead, exhibiting inhibition of MTB DNA gyrase supercoiling assay with an IC50 (50% inhibitory concentration) of 3.6 ± 0.16 μM, a Mycobacterium smegmatis GyrB IC50 of 10.6 ± 0.6 μM, and MTB minimum inhibitory concentrations of 6.95 μM and 10 μM against drug-sensitive (MTB H37Rv) and extensively drug-resistant strains, respectively. 24434114 4 14 theme aminopiperidine 1166:1180 arg1 analogues 1182:1190 the otherwise cardiotoxic N-linked aminopiperidine analogues 1131:1190 the otherwise cardiotoxic N-linked aminopiperidine analogues 1131:1190 Furthermore, the compounds did not show any signs of cardiotoxicity in zebrafish ether-à-go-go-related gene (zERG), and hence constitute a major breakthrough among the otherwise cardiotoxic N-linked aminopiperidine analogues. 24434114 4 15 theme cardiotoxicity 1020:1033 arg1 signs 1011:1015 any signs 1007:1015 any signs of cardiotoxicity in zebrafish ether-à-go-go-related gene (zERG) 1007:1080 Furthermore, the compounds did not show any signs of cardiotoxicity in zebrafish ether-à-go-go-related gene (zERG), and hence constitute a major breakthrough among the otherwise cardiotoxic N-linked aminopiperidine analogues. 24434114 3 16 theme 0.16 752:755 arg1 ± 750:750 ± 750:750 ± 750:750 Compound 5-fluoro-1-(2-(4-(4-(trifluoromethyl)benzylamino)piperidin-1-yl)ethyl)indoline-2,3-dione (17) emerged as the most potent lead, exhibiting inhibition of MTB DNA gyrase supercoiling assay with an IC50 (50% inhibitory concentration) of 3.6 ± 0.16 μM, a Mycobacterium smegmatis GyrB IC50 of 10.6 ± 0.6 μM, and MTB minimum inhibitory concentrations of 6.95 μM and 10 μM against drug-sensitive (MTB H37Rv) and extensively drug-resistant strains, respectively. 24434114 2 17 theme DNA 407:409 arg1 inhibitors 418:427 mycobacterial DNA gyrase inhibitors 393:427 mycobacterial DNA gyrase inhibitors with a high degree of specificity towards the mycobacterial ATPase domain 393:501 We present the discovery and optimisation of a novel series of mycobacterial DNA gyrase inhibitors with a high degree of specificity towards the mycobacterial ATPase domain. 24434114 2 18 theme series 383:388 arg1 discovery 345:353 discovery 345:353 discovery 345:353 We present the discovery and optimisation of a novel series of mycobacterial DNA gyrase inhibitors with a high degree of specificity towards the mycobacterial ATPase domain. 24434114 2 18 theme series 383:388 arg1 optimisation 359:370 optimisation 359:370 optimisation 359:370 We present the discovery and optimisation of a novel series of mycobacterial DNA gyrase inhibitors with a high degree of specificity towards the mycobacterial ATPase domain. 24434114 4 19 link N-linked 1157:1164 arg1 analogues 1182:1190 the otherwise cardiotoxic N-linked aminopiperidine analogues 1131:1190 the otherwise cardiotoxic N-linked aminopiperidine analogues 1131:1190 Furthermore, the compounds did not show any signs of cardiotoxicity in zebrafish ether-à-go-go-related gene (zERG), and hence constitute a major breakthrough among the otherwise cardiotoxic N-linked aminopiperidine analogues. 24434114 3 20 theme MTB 665:667 arg1 gyrase 673:678 MTB DNA gyrase 665:678 MTB DNA gyrase supercoiling assay with an IC50 (50% inhibitory concentration) of 3.6 ± 0.16 μM 665:758 Compound 5-fluoro-1-(2-(4-(4-(trifluoromethyl)benzylamino)piperidin-1-yl)ethyl)indoline-2,3-dione (17) emerged as the most potent lead, exhibiting inhibition of MTB DNA gyrase supercoiling assay with an IC50 (50% inhibitory concentration) of 3.6 ± 0.16 μM, a Mycobacterium smegmatis GyrB IC50 of 10.6 ± 0.6 μM, and MTB minimum inhibitory concentrations of 6.95 μM and 10 μM against drug-sensitive (MTB H37Rv) and extensively drug-resistant strains, respectively. 24434114 3 21 theme μM 757:758 arg1 concentration 728:740 50% inhibitory concentration 713:740 50% inhibitory concentration 713:740 Compound 5-fluoro-1-(2-(4-(4-(trifluoromethyl)benzylamino)piperidin-1-yl)ethyl)indoline-2,3-dione (17) emerged as the most potent lead, exhibiting inhibition of MTB DNA gyrase supercoiling assay with an IC50 (50% inhibitory concentration) of 3.6 ± 0.16 μM, a Mycobacterium smegmatis GyrB IC50 of 10.6 ± 0.6 μM, and MTB minimum inhibitory concentrations of 6.95 μM and 10 μM against drug-sensitive (MTB H37Rv) and extensively drug-resistant strains, respectively. 24434114 3 21 theme μM 757:758 arg1 IC50 707:710 an IC50 704:710 an IC50 (50% inhibitory concentration) of 3.6 ± 0.16 μM 704:758 Compound 5-fluoro-1-(2-(4-(4-(trifluoromethyl)benzylamino)piperidin-1-yl)ethyl)indoline-2,3-dione (17) emerged as the most potent lead, exhibiting inhibition of MTB DNA gyrase supercoiling assay with an IC50 (50% inhibitory concentration) of 3.6 ± 0.16 μM, a Mycobacterium smegmatis GyrB IC50 of 10.6 ± 0.6 μM, and MTB minimum inhibitory concentrations of 6.95 μM and 10 μM against drug-sensitive (MTB H37Rv) and extensively drug-resistant strains, respectively. 24434114 3 22 theme drug-resistant 929:942 arg1 strains 944:950 drug-sensitive (MTB H37Rv) and extensively drug-resistant strains 886:950 drug-sensitive (MTB H37Rv) and extensively drug-resistant strains 886:950 Compound 5-fluoro-1-(2-(4-(4-(trifluoromethyl)benzylamino)piperidin-1-yl)ethyl)indoline-2,3-dione (17) emerged as the most potent lead, exhibiting inhibition of MTB DNA gyrase supercoiling assay with an IC50 (50% inhibitory concentration) of 3.6 ± 0.16 μM, a Mycobacterium smegmatis GyrB IC50 of 10.6 ± 0.6 μM, and MTB minimum inhibitory concentrations of 6.95 μM and 10 μM against drug-sensitive (MTB H37Rv) and extensively drug-resistant strains, respectively. 24434114 2 23 theme high 436:439 arg1 degree 441:446 a high degree 434:446 a high degree of specificity towards the mycobacterial ATPase domain 434:501 We present the discovery and optimisation of a novel series of mycobacterial DNA gyrase inhibitors with a high degree of specificity towards the mycobacterial ATPase domain. 24434114 4 24 theme zebrafish 1038:1046 arg1 zERG 1076:1079 zERG 1076:1079 zERG 1076:1079 Furthermore, the compounds did not show any signs of cardiotoxicity in zebrafish ether-à-go-go-related gene (zERG), and hence constitute a major breakthrough among the otherwise cardiotoxic N-linked aminopiperidine analogues. 24434114 4 24 theme zebrafish 1038:1046 arg1 gene 1070:1073 zebrafish ether-à-go-go-related gene 1038:1073 zebrafish ether-à-go-go-related gene (zERG) 1038:1080 Furthermore, the compounds did not show any signs of cardiotoxicity in zebrafish ether-à-go-go-related gene (zERG), and hence constitute a major breakthrough among the otherwise cardiotoxic N-linked aminopiperidine analogues. 24434114 2 25 theme novel 377:381 arg1 series 383:388 a novel series 375:388 a novel series of mycobacterial DNA gyrase inhibitors with a high degree of specificity towards the mycobacterial ATPase domain 375:501 We present the discovery and optimisation of a novel series of mycobacterial DNA gyrase inhibitors with a high degree of specificity towards the mycobacterial ATPase domain. 24434114 2 26 theme inhibitors 418:427 arg1 series 383:388 a novel series 375:388 a novel series of mycobacterial DNA gyrase inhibitors with a high degree of specificity towards the mycobacterial ATPase domain 375:501 We present the discovery and optimisation of a novel series of mycobacterial DNA gyrase inhibitors with a high degree of specificity towards the mycobacterial ATPase domain. 24434114 3 27 theme DNA 669:671 arg1 gyrase 673:678 MTB DNA gyrase 665:678 MTB DNA gyrase supercoiling assay with an IC50 (50% inhibitory concentration) of 3.6 ± 0.16 μM 665:758 Compound 5-fluoro-1-(2-(4-(4-(trifluoromethyl)benzylamino)piperidin-1-yl)ethyl)indoline-2,3-dione (17) emerged as the most potent lead, exhibiting inhibition of MTB DNA gyrase supercoiling assay with an IC50 (50% inhibitory concentration) of 3.6 ± 0.16 μM, a Mycobacterium smegmatis GyrB IC50 of 10.6 ± 0.6 μM, and MTB minimum inhibitory concentrations of 6.95 μM and 10 μM against drug-sensitive (MTB H37Rv) and extensively drug-resistant strains, respectively. 24434114 4 28 from signs 1011:1015 arg1 zERG 1076:1079 zERG 1076:1079 zERG 1076:1079 Furthermore, the compounds did not show any signs of cardiotoxicity in zebrafish ether-à-go-go-related gene (zERG), and hence constitute a major breakthrough among the otherwise cardiotoxic N-linked aminopiperidine analogues. 24434114 4 28 from signs 1011:1015 arg1 gene 1070:1073 zebrafish ether-à-go-go-related gene 1038:1073 zebrafish ether-à-go-go-related gene (zERG) 1038:1080 Furthermore, the compounds did not show any signs of cardiotoxicity in zebrafish ether-à-go-go-related gene (zERG), and hence constitute a major breakthrough among the otherwise cardiotoxic N-linked aminopiperidine analogues. 24434114 3 29 theme trifluoromethyl 534:548 arg1 5-fluoro-1- 513:523 Compound 5-fluoro-1- 504:523 Compound 5-fluoro-1-(2-(4-(4-(trifluoromethyl)benzylamino)piperidin-1-yl)ethyl)indoline-2,3-dione (17) 504:605 Compound 5-fluoro-1-(2-(4-(4-(trifluoromethyl)benzylamino)piperidin-1-yl)ethyl)indoline-2,3-dione (17) emerged as the most potent lead, exhibiting inhibition of MTB DNA gyrase supercoiling assay with an IC50 (50% inhibitory concentration) of 3.6 ± 0.16 μM, a Mycobacterium smegmatis GyrB IC50 of 10.6 ± 0.6 μM, and MTB minimum inhibitory concentrations of 6.95 μM and 10 μM against drug-sensitive (MTB H37Rv) and extensively drug-resistant strains, respectively. 24434114 3 29 theme trifluoromethyl 534:548 arg1 ethyl 577:581 2-(4-(4-(trifluoromethyl)benzylamino)piperidin-1-yl)ethyl 525:581 2-(4-(4-(trifluoromethyl)benzylamino)piperidin-1-yl)ethyl 525:581 Compound 5-fluoro-1-(2-(4-(4-(trifluoromethyl)benzylamino)piperidin-1-yl)ethyl)indoline-2,3-dione (17) emerged as the most potent lead, exhibiting inhibition of MTB DNA gyrase supercoiling assay with an IC50 (50% inhibitory concentration) of 3.6 ± 0.16 μM, a Mycobacterium smegmatis GyrB IC50 of 10.6 ± 0.6 μM, and MTB minimum inhibitory concentrations of 6.95 μM and 10 μM against drug-sensitive (MTB H37Rv) and extensively drug-resistant strains, respectively. 24434114 3 30 theme μM 811:812 arg1 inhibition 651:660 inhibition 651:660 inhibition of MTB DNA gyrase supercoiling assay with an IC50 (50% inhibitory concentration) of 3.6 ± 0.16 μM 651:758 Compound 5-fluoro-1-(2-(4-(4-(trifluoromethyl)benzylamino)piperidin-1-yl)ethyl)indoline-2,3-dione (17) emerged as the most potent lead, exhibiting inhibition of MTB DNA gyrase supercoiling assay with an IC50 (50% inhibitory concentration) of 3.6 ± 0.16 μM, a Mycobacterium smegmatis GyrB IC50 of 10.6 ± 0.6 μM, and MTB minimum inhibitory concentrations of 6.95 μM and 10 μM against drug-sensitive (MTB H37Rv) and extensively drug-resistant strains, respectively. 24434114 3 30 theme μM 811:812 arg1 IC50 792:795 a Mycobacterium smegmatis GyrB IC50 761:795 a Mycobacterium smegmatis GyrB IC50 of 10.6 ± 0.6 μM 761:812 Compound 5-fluoro-1-(2-(4-(4-(trifluoromethyl)benzylamino)piperidin-1-yl)ethyl)indoline-2,3-dione (17) emerged as the most potent lead, exhibiting inhibition of MTB DNA gyrase supercoiling assay with an IC50 (50% inhibitory concentration) of 3.6 ± 0.16 μM, a Mycobacterium smegmatis GyrB IC50 of 10.6 ± 0.6 μM, and MTB minimum inhibitory concentrations of 6.95 μM and 10 μM against drug-sensitive (MTB H37Rv) and extensively drug-resistant strains, respectively. 24434114 3 30 theme μM 811:812 arg1 concentrations 842:855 MTB minimum inhibitory concentrations 819:855 MTB minimum inhibitory concentrations of 6.95 μM and 10 μM against drug-sensitive (MTB H37Rv) and extensively drug-resistant strains, respectively 819:964 Compound 5-fluoro-1-(2-(4-(4-(trifluoromethyl)benzylamino)piperidin-1-yl)ethyl)indoline-2,3-dione (17) emerged as the most potent lead, exhibiting inhibition of MTB DNA gyrase supercoiling assay with an IC50 (50% inhibitory concentration) of 3.6 ± 0.16 μM, a Mycobacterium smegmatis GyrB IC50 of 10.6 ± 0.6 μM, and MTB minimum inhibitory concentrations of 6.95 μM and 10 μM against drug-sensitive (MTB H37Rv) and extensively drug-resistant strains, respectively. 24434114 3 31 theme potent 627:632 arg1 lead 634:637 the most potent lead 618:637 the most potent lead 618:637 Compound 5-fluoro-1-(2-(4-(4-(trifluoromethyl)benzylamino)piperidin-1-yl)ethyl)indoline-2,3-dione (17) emerged as the most potent lead, exhibiting inhibition of MTB DNA gyrase supercoiling assay with an IC50 (50% inhibitory concentration) of 3.6 ± 0.16 μM, a Mycobacterium smegmatis GyrB IC50 of 10.6 ± 0.6 μM, and MTB minimum inhibitory concentrations of 6.95 μM and 10 μM against drug-sensitive (MTB H37Rv) and extensively drug-resistant strains, respectively. 24434114 3 32 theme inhibitory 831:840 arg1 concentrations 842:855 MTB minimum inhibitory concentrations 819:855 MTB minimum inhibitory concentrations of 6.95 μM and 10 μM against drug-sensitive (MTB H37Rv) and extensively drug-resistant strains, respectively 819:964 Compound 5-fluoro-1-(2-(4-(4-(trifluoromethyl)benzylamino)piperidin-1-yl)ethyl)indoline-2,3-dione (17) emerged as the most potent lead, exhibiting inhibition of MTB DNA gyrase supercoiling assay with an IC50 (50% inhibitory concentration) of 3.6 ± 0.16 μM, a Mycobacterium smegmatis GyrB IC50 of 10.6 ± 0.6 μM, and MTB minimum inhibitory concentrations of 6.95 μM and 10 μM against drug-sensitive (MTB H37Rv) and extensively drug-resistant strains, respectively. 24434114 0 33 theme N-linked 21:28 arg1 inhibitors 79:88 novel N-linked aminopiperidine-based mycobacterial DNA gyrase B inhibitors 15:88 novel N-linked aminopiperidine-based mycobacterial DNA gyrase B inhibitors 15:88 Development of novel N-linked aminopiperidine-based mycobacterial DNA gyrase B inhibitors: scaffold hopping from known antibacterial leads. 24434114 3 34 theme MTB 902:904 arg1 H37Rv 906:910 MTB H37Rv 902:910 MTB H37Rv 902:910 Compound 5-fluoro-1-(2-(4-(4-(trifluoromethyl)benzylamino)piperidin-1-yl)ethyl)indoline-2,3-dione (17) emerged as the most potent lead, exhibiting inhibition of MTB DNA gyrase supercoiling assay with an IC50 (50% inhibitory concentration) of 3.6 ± 0.16 μM, a Mycobacterium smegmatis GyrB IC50 of 10.6 ± 0.6 μM, and MTB minimum inhibitory concentrations of 6.95 μM and 10 μM against drug-sensitive (MTB H37Rv) and extensively drug-resistant strains, respectively. 24434114 3 35 dep 5-fluoro-1- 513:523 arg1 indoline-2,3-dione 583:600 indoline-2,3-dione (17) 583:605 Compound 5-fluoro-1-(2-(4-(4-(trifluoromethyl)benzylamino)piperidin-1-yl)ethyl)indoline-2,3-dione (17) 504:605 Compound 5-fluoro-1-(2-(4-(4-(trifluoromethyl)benzylamino)piperidin-1-yl)ethyl)indoline-2,3-dione (17) emerged as the most potent lead, exhibiting inhibition of MTB DNA gyrase supercoiling assay with an IC50 (50% inhibitory concentration) of 3.6 ± 0.16 μM, a Mycobacterium smegmatis GyrB IC50 of 10.6 ± 0.6 μM, and MTB minimum inhibitory concentrations of 6.95 μM and 10 μM against drug-sensitive (MTB H37Rv) and extensively drug-resistant strains, respectively. 24434114 1 36 theme type 192:195 arg1 target 322:327 a bactericidal drug target 302:327 a bactericidal drug target 302:327 DNA gyrase of Mycobacterium tuberculosis (MTB) is a type II topoisomerase that ensures the regulation of DNA topology and has been genetically demonstrated to be a bactericidal drug target. 24434114 1 36 theme type 192:195 arg1 gyrase 144:149 DNA gyrase 140:149 DNA gyrase of Mycobacterium tuberculosis (MTB) 140:185 DNA gyrase of Mycobacterium tuberculosis (MTB) is a type II topoisomerase that ensures the regulation of DNA topology and has been genetically demonstrated to be a bactericidal drug target. 24434114 1 36 theme type 192:195 arg1 topoisomerase 200:212 a type II topoisomerase 190:212 a type II topoisomerase that ensures the regulation of DNA topology and has been genetically demonstrated to be a bactericidal drug target 190:327 DNA gyrase of Mycobacterium tuberculosis (MTB) is a type II topoisomerase that ensures the regulation of DNA topology and has been genetically demonstrated to be a bactericidal drug target. 24434114 0 37 theme novel 15:19 arg1 inhibitors 79:88 novel N-linked aminopiperidine-based mycobacterial DNA gyrase B inhibitors 15:88 novel N-linked aminopiperidine-based mycobacterial DNA gyrase B inhibitors 15:88 Development of novel N-linked aminopiperidine-based mycobacterial DNA gyrase B inhibitors: scaffold hopping from known antibacterial leads. 24434114 3 38 dep drug-sensitive 886:899 arg1 H37Rv 906:910 MTB H37Rv 902:910 MTB H37Rv 902:910 Compound 5-fluoro-1-(2-(4-(4-(trifluoromethyl)benzylamino)piperidin-1-yl)ethyl)indoline-2,3-dione (17) emerged as the most potent lead, exhibiting inhibition of MTB DNA gyrase supercoiling assay with an IC50 (50% inhibitory concentration) of 3.6 ± 0.16 μM, a Mycobacterium smegmatis GyrB IC50 of 10.6 ± 0.6 μM, and MTB minimum inhibitory concentrations of 6.95 μM and 10 μM against drug-sensitive (MTB H37Rv) and extensively drug-resistant strains, respectively. 24434114 3 39 theme MTB 819:821 arg1 concentrations 842:855 MTB minimum inhibitory concentrations 819:855 MTB minimum inhibitory concentrations of 6.95 μM and 10 μM against drug-sensitive (MTB H37Rv) and extensively drug-resistant strains, respectively 819:964 Compound 5-fluoro-1-(2-(4-(4-(trifluoromethyl)benzylamino)piperidin-1-yl)ethyl)indoline-2,3-dione (17) emerged as the most potent lead, exhibiting inhibition of MTB DNA gyrase supercoiling assay with an IC50 (50% inhibitory concentration) of 3.6 ± 0.16 μM, a Mycobacterium smegmatis GyrB IC50 of 10.6 ± 0.6 μM, and MTB minimum inhibitory concentrations of 6.95 μM and 10 μM against drug-sensitive (MTB H37Rv) and extensively drug-resistant strains, respectively. 24434114 1 40 theme II 197:198 arg1 target 322:327 a bactericidal drug target 302:327 a bactericidal drug target 302:327 DNA gyrase of Mycobacterium tuberculosis (MTB) is a type II topoisomerase that ensures the regulation of DNA topology and has been genetically demonstrated to be a bactericidal drug target. 24434114 1 40 theme II 197:198 arg1 gyrase 144:149 DNA gyrase 140:149 DNA gyrase of Mycobacterium tuberculosis (MTB) 140:185 DNA gyrase of Mycobacterium tuberculosis (MTB) is a type II topoisomerase that ensures the regulation of DNA topology and has been genetically demonstrated to be a bactericidal drug target. 24434114 1 40 theme II 197:198 arg1 topoisomerase 200:212 a type II topoisomerase 190:212 a type II topoisomerase that ensures the regulation of DNA topology and has been genetically demonstrated to be a bactericidal drug target 190:327 DNA gyrase of Mycobacterium tuberculosis (MTB) is a type II topoisomerase that ensures the regulation of DNA topology and has been genetically demonstrated to be a bactericidal drug target. 24434114 0 41 theme mycobacterial 52:64 arg1 inhibitors 79:88 novel N-linked aminopiperidine-based mycobacterial DNA gyrase B inhibitors 15:88 novel N-linked aminopiperidine-based mycobacterial DNA gyrase B inhibitors 15:88 Development of novel N-linked aminopiperidine-based mycobacterial DNA gyrase B inhibitors: scaffold hopping from known antibacterial leads. 24434114 3 42 theme piperidin-1-yl 562:575 arg1 5-fluoro-1- 513:523 Compound 5-fluoro-1- 504:523 Compound 5-fluoro-1-(2-(4-(4-(trifluoromethyl)benzylamino)piperidin-1-yl)ethyl)indoline-2,3-dione (17) 504:605 Compound 5-fluoro-1-(2-(4-(4-(trifluoromethyl)benzylamino)piperidin-1-yl)ethyl)indoline-2,3-dione (17) emerged as the most potent lead, exhibiting inhibition of MTB DNA gyrase supercoiling assay with an IC50 (50% inhibitory concentration) of 3.6 ± 0.16 μM, a Mycobacterium smegmatis GyrB IC50 of 10.6 ± 0.6 μM, and MTB minimum inhibitory concentrations of 6.95 μM and 10 μM against drug-sensitive (MTB H37Rv) and extensively drug-resistant strains, respectively. 24434114 3 42 theme piperidin-1-yl 562:575 arg1 ethyl 577:581 2-(4-(4-(trifluoromethyl)benzylamino)piperidin-1-yl)ethyl 525:581 2-(4-(4-(trifluoromethyl)benzylamino)piperidin-1-yl)ethyl 525:581 Compound 5-fluoro-1-(2-(4-(4-(trifluoromethyl)benzylamino)piperidin-1-yl)ethyl)indoline-2,3-dione (17) emerged as the most potent lead, exhibiting inhibition of MTB DNA gyrase supercoiling assay with an IC50 (50% inhibitory concentration) of 3.6 ± 0.16 μM, a Mycobacterium smegmatis GyrB IC50 of 10.6 ± 0.6 μM, and MTB minimum inhibitory concentrations of 6.95 μM and 10 μM against drug-sensitive (MTB H37Rv) and extensively drug-resistant strains, respectively. 24434114 3 43 theme minimum 823:829 arg1 concentrations 842:855 MTB minimum inhibitory concentrations 819:855 MTB minimum inhibitory concentrations of 6.95 μM and 10 μM against drug-sensitive (MTB H37Rv) and extensively drug-resistant strains, respectively 819:964 Compound 5-fluoro-1-(2-(4-(4-(trifluoromethyl)benzylamino)piperidin-1-yl)ethyl)indoline-2,3-dione (17) emerged as the most potent lead, exhibiting inhibition of MTB DNA gyrase supercoiling assay with an IC50 (50% inhibitory concentration) of 3.6 ± 0.16 μM, a Mycobacterium smegmatis GyrB IC50 of 10.6 ± 0.6 μM, and MTB minimum inhibitory concentrations of 6.95 μM and 10 μM against drug-sensitive (MTB H37Rv) and extensively drug-resistant strains, respectively. 24434114 2 44 theme mycobacterial 393:405 arg1 inhibitors 418:427 mycobacterial DNA gyrase inhibitors 393:427 mycobacterial DNA gyrase inhibitors with a high degree of specificity towards the mycobacterial ATPase domain 393:501 We present the discovery and optimisation of a novel series of mycobacterial DNA gyrase inhibitors with a high degree of specificity towards the mycobacterial ATPase domain. 24434114 0 45 theme aminopiperidine-based 30:50 arg1 inhibitors 79:88 novel N-linked aminopiperidine-based mycobacterial DNA gyrase B inhibitors 15:88 novel N-linked aminopiperidine-based mycobacterial DNA gyrase B inhibitors 15:88 Development of novel N-linked aminopiperidine-based mycobacterial DNA gyrase B inhibitors: scaffold hopping from known antibacterial leads. 24434114 3 46 theme % 715:715 arg1 concentration 728:740 50% inhibitory concentration 713:740 50% inhibitory concentration 713:740 Compound 5-fluoro-1-(2-(4-(4-(trifluoromethyl)benzylamino)piperidin-1-yl)ethyl)indoline-2,3-dione (17) emerged as the most potent lead, exhibiting inhibition of MTB DNA gyrase supercoiling assay with an IC50 (50% inhibitory concentration) of 3.6 ± 0.16 μM, a Mycobacterium smegmatis GyrB IC50 of 10.6 ± 0.6 μM, and MTB minimum inhibitory concentrations of 6.95 μM and 10 μM against drug-sensitive (MTB H37Rv) and extensively drug-resistant strains, respectively. 24434114 3 46 theme % 715:715 arg1 IC50 707:710 an IC50 704:710 an IC50 (50% inhibitory concentration) of 3.6 ± 0.16 μM 704:758 Compound 5-fluoro-1-(2-(4-(4-(trifluoromethyl)benzylamino)piperidin-1-yl)ethyl)indoline-2,3-dione (17) emerged as the most potent lead, exhibiting inhibition of MTB DNA gyrase supercoiling assay with an IC50 (50% inhibitory concentration) of 3.6 ± 0.16 μM, a Mycobacterium smegmatis GyrB IC50 of 10.6 ± 0.6 μM, and MTB minimum inhibitory concentrations of 6.95 μM and 10 μM against drug-sensitive (MTB H37Rv) and extensively drug-resistant strains, respectively. 24434114 2 47 theme specificity 451:461 arg1 degree 441:446 a high degree 434:446 a high degree of specificity towards the mycobacterial ATPase domain 434:501 We present the discovery and optimisation of a novel series of mycobacterial DNA gyrase inhibitors with a high degree of specificity towards the mycobacterial ATPase domain. 24434114 3 48 theme μM 865:866 arg1 inhibition 651:660 inhibition 651:660 inhibition of MTB DNA gyrase supercoiling assay with an IC50 (50% inhibitory concentration) of 3.6 ± 0.16 μM 651:758 Compound 5-fluoro-1-(2-(4-(4-(trifluoromethyl)benzylamino)piperidin-1-yl)ethyl)indoline-2,3-dione (17) emerged as the most potent lead, exhibiting inhibition of MTB DNA gyrase supercoiling assay with an IC50 (50% inhibitory concentration) of 3.6 ± 0.16 μM, a Mycobacterium smegmatis GyrB IC50 of 10.6 ± 0.6 μM, and MTB minimum inhibitory concentrations of 6.95 μM and 10 μM against drug-sensitive (MTB H37Rv) and extensively drug-resistant strains, respectively. 24434114 3 48 theme μM 865:866 arg1 IC50 792:795 a Mycobacterium smegmatis GyrB IC50 761:795 a Mycobacterium smegmatis GyrB IC50 of 10.6 ± 0.6 μM 761:812 Compound 5-fluoro-1-(2-(4-(4-(trifluoromethyl)benzylamino)piperidin-1-yl)ethyl)indoline-2,3-dione (17) emerged as the most potent lead, exhibiting inhibition of MTB DNA gyrase supercoiling assay with an IC50 (50% inhibitory concentration) of 3.6 ± 0.16 μM, a Mycobacterium smegmatis GyrB IC50 of 10.6 ± 0.6 μM, and MTB minimum inhibitory concentrations of 6.95 μM and 10 μM against drug-sensitive (MTB H37Rv) and extensively drug-resistant strains, respectively. 24434114 3 48 theme μM 865:866 arg1 concentrations 842:855 MTB minimum inhibitory concentrations 819:855 MTB minimum inhibitory concentrations of 6.95 μM and 10 μM against drug-sensitive (MTB H37Rv) and extensively drug-resistant strains, respectively 819:964 Compound 5-fluoro-1-(2-(4-(4-(trifluoromethyl)benzylamino)piperidin-1-yl)ethyl)indoline-2,3-dione (17) emerged as the most potent lead, exhibiting inhibition of MTB DNA gyrase supercoiling assay with an IC50 (50% inhibitory concentration) of 3.6 ± 0.16 μM, a Mycobacterium smegmatis GyrB IC50 of 10.6 ± 0.6 μM, and MTB minimum inhibitory concentrations of 6.95 μM and 10 μM against drug-sensitive (MTB H37Rv) and extensively drug-resistant strains, respectively. 24434114 0 49 theme gyrase 70:75 arg1 inhibitors 79:88 novel N-linked aminopiperidine-based mycobacterial DNA gyrase B inhibitors 15:88 novel N-linked aminopiperidine-based mycobacterial DNA gyrase B inhibitors 15:88 Development of novel N-linked aminopiperidine-based mycobacterial DNA gyrase B inhibitors: scaffold hopping from known antibacterial leads. 24434114 3 50 theme inhibitory 717:726 arg1 concentration 728:740 50% inhibitory concentration 713:740 50% inhibitory concentration 713:740 Compound 5-fluoro-1-(2-(4-(4-(trifluoromethyl)benzylamino)piperidin-1-yl)ethyl)indoline-2,3-dione (17) emerged as the most potent lead, exhibiting inhibition of MTB DNA gyrase supercoiling assay with an IC50 (50% inhibitory concentration) of 3.6 ± 0.16 μM, a Mycobacterium smegmatis GyrB IC50 of 10.6 ± 0.6 μM, and MTB minimum inhibitory concentrations of 6.95 μM and 10 μM against drug-sensitive (MTB H37Rv) and extensively drug-resistant strains, respectively. 24434114 3 50 theme inhibitory 717:726 arg1 IC50 707:710 an IC50 704:710 an IC50 (50% inhibitory concentration) of 3.6 ± 0.16 μM 704:758 Compound 5-fluoro-1-(2-(4-(4-(trifluoromethyl)benzylamino)piperidin-1-yl)ethyl)indoline-2,3-dione (17) emerged as the most potent lead, exhibiting inhibition of MTB DNA gyrase supercoiling assay with an IC50 (50% inhibitory concentration) of 3.6 ± 0.16 μM, a Mycobacterium smegmatis GyrB IC50 of 10.6 ± 0.6 μM, and MTB minimum inhibitory concentrations of 6.95 μM and 10 μM against drug-sensitive (MTB H37Rv) and extensively drug-resistant strains, respectively. 24434114 2 51 theme ATPase 489:494 arg1 domain 496:501 the mycobacterial ATPase domain 471:501 the mycobacterial ATPase domain 471:501 We present the discovery and optimisation of a novel series of mycobacterial DNA gyrase inhibitors with a high degree of specificity towards the mycobacterial ATPase domain. 24434114 3 52 theme benzylamino 550:560 arg1 5-fluoro-1- 513:523 Compound 5-fluoro-1- 504:523 Compound 5-fluoro-1-(2-(4-(4-(trifluoromethyl)benzylamino)piperidin-1-yl)ethyl)indoline-2,3-dione (17) 504:605 Compound 5-fluoro-1-(2-(4-(4-(trifluoromethyl)benzylamino)piperidin-1-yl)ethyl)indoline-2,3-dione (17) emerged as the most potent lead, exhibiting inhibition of MTB DNA gyrase supercoiling assay with an IC50 (50% inhibitory concentration) of 3.6 ± 0.16 μM, a Mycobacterium smegmatis GyrB IC50 of 10.6 ± 0.6 μM, and MTB minimum inhibitory concentrations of 6.95 μM and 10 μM against drug-sensitive (MTB H37Rv) and extensively drug-resistant strains, respectively. 24434114 3 52 theme benzylamino 550:560 arg1 ethyl 577:581 2-(4-(4-(trifluoromethyl)benzylamino)piperidin-1-yl)ethyl 525:581 2-(4-(4-(trifluoromethyl)benzylamino)piperidin-1-yl)ethyl 525:581 Compound 5-fluoro-1-(2-(4-(4-(trifluoromethyl)benzylamino)piperidin-1-yl)ethyl)indoline-2,3-dione (17) emerged as the most potent lead, exhibiting inhibition of MTB DNA gyrase supercoiling assay with an IC50 (50% inhibitory concentration) of 3.6 ± 0.16 μM, a Mycobacterium smegmatis GyrB IC50 of 10.6 ± 0.6 μM, and MTB minimum inhibitory concentrations of 6.95 μM and 10 μM against drug-sensitive (MTB H37Rv) and extensively drug-resistant strains, respectively. 24434114 2 53 with inhibitors 418:427 arg1 degree 441:446 a high degree 434:446 a high degree of specificity towards the mycobacterial ATPase domain 434:501 We present the discovery and optimisation of a novel series of mycobacterial DNA gyrase inhibitors with a high degree of specificity towards the mycobacterial ATPase domain. 24434114 0 54 theme DNA 66:68 arg1 inhibitors 79:88 novel N-linked aminopiperidine-based mycobacterial DNA gyrase B inhibitors 15:88 novel N-linked aminopiperidine-based mycobacterial DNA gyrase B inhibitors 15:88 Development of novel N-linked aminopiperidine-based mycobacterial DNA gyrase B inhibitors: scaffold hopping from known antibacterial leads. 24434114 1 55 theme bactericidal 304:315 arg1 target 322:327 a bactericidal drug target 302:327 a bactericidal drug target 302:327 DNA gyrase of Mycobacterium tuberculosis (MTB) is a type II topoisomerase that ensures the regulation of DNA topology and has been genetically demonstrated to be a bactericidal drug target. 24434114 1 55 theme bactericidal 304:315 arg1 gyrase 144:149 DNA gyrase 140:149 DNA gyrase of Mycobacterium tuberculosis (MTB) 140:185 DNA gyrase of Mycobacterium tuberculosis (MTB) is a type II topoisomerase that ensures the regulation of DNA topology and has been genetically demonstrated to be a bactericidal drug target. 24434114 1 55 theme bactericidal 304:315 arg1 topoisomerase 200:212 a type II topoisomerase 190:212 a type II topoisomerase that ensures the regulation of DNA topology and has been genetically demonstrated to be a bactericidal drug target 190:327 DNA gyrase of Mycobacterium tuberculosis (MTB) is a type II topoisomerase that ensures the regulation of DNA topology and has been genetically demonstrated to be a bactericidal drug target. 24434114 0 56 from antibacterial 119:131 arg1 hopping 100:106 scaffold hopping 91:106 Development of novel N-linked aminopiperidine-based mycobacterial DNA gyrase B inhibitors: scaffold hopping from known antibacterial leads. 0:138 Development of novel N-linked aminopiperidine-based mycobacterial DNA gyrase B inhibitors: scaffold hopping from known antibacterial leads. 24434114 3 57 theme smegmatis 777:785 arg1 IC50 792:795 a Mycobacterium smegmatis GyrB IC50 761:795 a Mycobacterium smegmatis GyrB IC50 of 10.6 ± 0.6 μM 761:812 Compound 5-fluoro-1-(2-(4-(4-(trifluoromethyl)benzylamino)piperidin-1-yl)ethyl)indoline-2,3-dione (17) emerged as the most potent lead, exhibiting inhibition of MTB DNA gyrase supercoiling assay with an IC50 (50% inhibitory concentration) of 3.6 ± 0.16 μM, a Mycobacterium smegmatis GyrB IC50 of 10.6 ± 0.6 μM, and MTB minimum inhibitory concentrations of 6.95 μM and 10 μM against drug-sensitive (MTB H37Rv) and extensively drug-resistant strains, respectively. 24434114 1 58 theme drug 317:320 arg1 target 322:327 a bactericidal drug target 302:327 a bactericidal drug target 302:327 DNA gyrase of Mycobacterium tuberculosis (MTB) is a type II topoisomerase that ensures the regulation of DNA topology and has been genetically demonstrated to be a bactericidal drug target. 24434114 1 58 theme drug 317:320 arg1 gyrase 144:149 DNA gyrase 140:149 DNA gyrase of Mycobacterium tuberculosis (MTB) 140:185 DNA gyrase of Mycobacterium tuberculosis (MTB) is a type II topoisomerase that ensures the regulation of DNA topology and has been genetically demonstrated to be a bactericidal drug target. 24434114 1 58 theme drug 317:320 arg1 topoisomerase 200:212 a type II topoisomerase 190:212 a type II topoisomerase that ensures the regulation of DNA topology and has been genetically demonstrated to be a bactericidal drug target 190:327 DNA gyrase of Mycobacterium tuberculosis (MTB) is a type II topoisomerase that ensures the regulation of DNA topology and has been genetically demonstrated to be a bactericidal drug target. 24434114 4 59 theme N-linked 1157:1164 arg1 analogues 1182:1190 the otherwise cardiotoxic N-linked aminopiperidine analogues 1131:1190 the otherwise cardiotoxic N-linked aminopiperidine analogues 1131:1190 Furthermore, the compounds did not show any signs of cardiotoxicity in zebrafish ether-à-go-go-related gene (zERG), and hence constitute a major breakthrough among the otherwise cardiotoxic N-linked aminopiperidine analogues. 24434114 3 60 theme drug-sensitive 886:899 arg1 strains 944:950 drug-sensitive (MTB H37Rv) and extensively drug-resistant strains 886:950 drug-sensitive (MTB H37Rv) and extensively drug-resistant strains 886:950 Compound 5-fluoro-1-(2-(4-(4-(trifluoromethyl)benzylamino)piperidin-1-yl)ethyl)indoline-2,3-dione (17) emerged as the most potent lead, exhibiting inhibition of MTB DNA gyrase supercoiling assay with an IC50 (50% inhibitory concentration) of 3.6 ± 0.16 μM, a Mycobacterium smegmatis GyrB IC50 of 10.6 ± 0.6 μM, and MTB minimum inhibitory concentrations of 6.95 μM and 10 μM against drug-sensitive (MTB H37Rv) and extensively drug-resistant strains, respectively. 24434114 1 61 theme DNA 140:142 arg1 target 322:327 a bactericidal drug target 302:327 a bactericidal drug target 302:327 DNA gyrase of Mycobacterium tuberculosis (MTB) is a type II topoisomerase that ensures the regulation of DNA topology and has been genetically demonstrated to be a bactericidal drug target. 24434114 1 61 theme DNA 140:142 arg1 gyrase 144:149 DNA gyrase 140:149 DNA gyrase of Mycobacterium tuberculosis (MTB) 140:185 DNA gyrase of Mycobacterium tuberculosis (MTB) is a type II topoisomerase that ensures the regulation of DNA topology and has been genetically demonstrated to be a bactericidal drug target. 24434114 1 61 theme DNA 140:142 arg1 topoisomerase 200:212 a type II topoisomerase 190:212 a type II topoisomerase that ensures the regulation of DNA topology and has been genetically demonstrated to be a bactericidal drug target 190:327 DNA gyrase of Mycobacterium tuberculosis (MTB) is a type II topoisomerase that ensures the regulation of DNA topology and has been genetically demonstrated to be a bactericidal drug target. 24434114 3 62 theme GyrB 787:790 arg1 IC50 792:795 a Mycobacterium smegmatis GyrB IC50 761:795 a Mycobacterium smegmatis GyrB IC50 of 10.6 ± 0.6 μM 761:812 Compound 5-fluoro-1-(2-(4-(4-(trifluoromethyl)benzylamino)piperidin-1-yl)ethyl)indoline-2,3-dione (17) emerged as the most potent lead, exhibiting inhibition of MTB DNA gyrase supercoiling assay with an IC50 (50% inhibitory concentration) of 3.6 ± 0.16 μM, a Mycobacterium smegmatis GyrB IC50 of 10.6 ± 0.6 μM, and MTB minimum inhibitory concentrations of 6.95 μM and 10 μM against drug-sensitive (MTB H37Rv) and extensively drug-resistant strains, respectively. 24434114 2 63 dep discovery 345:353 arg1 the 341:343 the 341:343 the 341:343 We present the discovery and optimisation of a novel series of mycobacterial DNA gyrase inhibitors with a high degree of specificity towards the mycobacterial ATPase domain. 24434114 3 64 theme 3.6 746:748 arg1 ± 750:750 ± 750:750 ± 750:750 Compound 5-fluoro-1-(2-(4-(4-(trifluoromethyl)benzylamino)piperidin-1-yl)ethyl)indoline-2,3-dione (17) emerged as the most potent lead, exhibiting inhibition of MTB DNA gyrase supercoiling assay with an IC50 (50% inhibitory concentration) of 3.6 ± 0.16 μM, a Mycobacterium smegmatis GyrB IC50 of 10.6 ± 0.6 μM, and MTB minimum inhibitory concentrations of 6.95 μM and 10 μM against drug-sensitive (MTB H37Rv) and extensively drug-resistant strains, respectively. 24434114 0 65 theme inhibitors 79:88 arg1 Development 0:10 Development 0:10 Development of novel N-linked aminopiperidine-based mycobacterial DNA gyrase B inhibitors: scaffold hopping from known antibacterial leads. 0:138 Development of novel N-linked aminopiperidine-based mycobacterial DNA gyrase B inhibitors: scaffold hopping from known antibacterial leads. 24434114 2 66 theme gyrase 411:416 arg1 inhibitors 418:427 mycobacterial DNA gyrase inhibitors 393:427 mycobacterial DNA gyrase inhibitors with a high degree of specificity towards the mycobacterial ATPase domain 393:501 We present the discovery and optimisation of a novel series of mycobacterial DNA gyrase inhibitors with a high degree of specificity towards the mycobacterial ATPase domain. 24434114 3 67 theme Mycobacterium 763:775 arg1 IC50 792:795 a Mycobacterium smegmatis GyrB IC50 761:795 a Mycobacterium smegmatis GyrB IC50 of 10.6 ± 0.6 μM 761:812 Compound 5-fluoro-1-(2-(4-(4-(trifluoromethyl)benzylamino)piperidin-1-yl)ethyl)indoline-2,3-dione (17) emerged as the most potent lead, exhibiting inhibition of MTB DNA gyrase supercoiling assay with an IC50 (50% inhibitory concentration) of 3.6 ± 0.16 μM, a Mycobacterium smegmatis GyrB IC50 of 10.6 ± 0.6 μM, and MTB minimum inhibitory concentrations of 6.95 μM and 10 μM against drug-sensitive (MTB H37Rv) and extensively drug-resistant strains, respectively. 24434114 0 68 theme B 77:77 arg1 inhibitors 79:88 novel N-linked aminopiperidine-based mycobacterial DNA gyrase B inhibitors 15:88 novel N-linked aminopiperidine-based mycobacterial DNA gyrase B inhibitors 15:88 Development of novel N-linked aminopiperidine-based mycobacterial DNA gyrase B inhibitors: scaffold hopping from known antibacterial leads. 24434114 0 69 dep Development 0:10 arg1 hopping 100:106 scaffold hopping 91:106 Development of novel N-linked aminopiperidine-based mycobacterial DNA gyrase B inhibitors: scaffold hopping from known antibacterial leads. 0:138 Development of novel N-linked aminopiperidine-based mycobacterial DNA gyrase B inhibitors: scaffold hopping from known antibacterial leads. 24434114 1 70 theme Mycobacterium 154:166 arg1 MTB 182:184 MTB 182:184 MTB 182:184 DNA gyrase of Mycobacterium tuberculosis (MTB) is a type II topoisomerase that ensures the regulation of DNA topology and has been genetically demonstrated to be a bactericidal drug target. 24434114 1 70 theme Mycobacterium 154:166 arg1 tuberculosis 168:179 Mycobacterium tuberculosis 154:179 Mycobacterium tuberculosis (MTB) 154:185 DNA gyrase of Mycobacterium tuberculosis (MTB) is a type II topoisomerase that ensures the regulation of DNA topology and has been genetically demonstrated to be a bactericidal drug target. 28688099 8 0 theme IκBSer32 1217:1224 arg1 expression 1188:1197 increased expression 1178:1197 increased expression of phosphorylated IκBSer32 1178:1224 Reduced expression of IκB and increased expression of phosphorylated IκBSer32 were observed in the placenta from hyperglycemic rats, demonstrating increased classical NF-κB activation. 28688099 8 0 theme IκBSer32 1217:1224 arg1 expression 1156:1165 Reduced expression 1148:1165 Reduced expression of IκB 1148:1172 Reduced expression of IκB and increased expression of phosphorylated IκBSer32 were observed in the placenta from hyperglycemic rats, demonstrating increased classical NF-κB activation. 28688099 6 1 theme p65 982:984 arg1 subunit 986:992 p65 subunit 982:992 p65 subunit 982:992 Placental expression of p65 subunit was similar between groups. 28688099 10 2 theme hyperglycemic 1628:1640 arg1 rats 1642:1645 hyperglycemic rats 1628:1645 hyperglycemic rats 1628:1645 Tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) expressions were increased in the placenta from hyperglycemic rats. 28688099 3 3 theme vehicle 750:756 arg1 injections 707:716 Single injections 700:716 Single injections of streptozotocin (40 mg/kg) or vehicle 700:756 Single injections of streptozotocin (40 mg/kg) or vehicle were used to induce hyperglycemia or normoglycemia, respectively, in female Wistar rats. 28688099 2 4 theme placental 648:656 arg1 dysfunction 658:668 placental dysfunction 648:668 placental dysfunction 648:668 We hypothesized that hyperglycemia-induced increased glycosylation with O-linked N-acetylglucosamine (O-GlcNAc) of NF-κB in placental tissue leads to augmented production of pro-inflammatory cytokines, culminating in placental dysfunction and fetal restriction growth. 28688099 13 5 theme hyperglycemic 1919:1931 arg1 conditions 1933:1942 hyperglycemic conditions 1919:1942 hyperglycemic conditions 1919:1942 Therefore, under hyperglycemic conditions, a modulatory role of O-GlcNAc in NF-κB activity was demonstrated in the placenta, contributing to fetal and placental dysfunction due to inflammatory cytokine exacerbation. 28688099 1 6 theme inhibitor 263:271 arg1 translocation 296:308 subsequent nuclear translocation 277:308 subsequent nuclear translocation 277:308 Inflammation as a result of NF-κB activation may result from the classical (canonical) pathway, with disconnection of the IκB inhibitor and subsequent nuclear translocation or, alternatively, by post-translational modifications of modulatory proteins or NF-κB subunits (non-canonical pathway). 28688099 1 6 theme inhibitor 263:271 arg1 disconnection 238:250 disconnection 238:250 disconnection of the IκB inhibitor 238:271 Inflammation as a result of NF-κB activation may result from the classical (canonical) pathway, with disconnection of the IκB inhibitor and subsequent nuclear translocation or, alternatively, by post-translational modifications of modulatory proteins or NF-κB subunits (non-canonical pathway). 28688099 10 7 theme necrosis 1525:1532 arg1 TNF-α 1548:1552 TNF-α 1548:1552 TNF-α 1548:1552 Tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) expressions were increased in the placenta from hyperglycemic rats. 28688099 10 7 theme necrosis 1525:1532 arg1 factor-alpha 1534:1545 Tumor necrosis factor-alpha 1519:1545 Tumor necrosis factor-alpha (TNF-α) 1519:1553 Tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) expressions were increased in the placenta from hyperglycemic rats. 28688099 2 8 theme restriction 680:690 arg1 growth 692:697 fetal restriction growth 674:697 fetal restriction growth 674:697 We hypothesized that hyperglycemia-induced increased glycosylation with O-linked N-acetylglucosamine (O-GlcNAc) of NF-κB in placental tissue leads to augmented production of pro-inflammatory cytokines, culminating in placental dysfunction and fetal restriction growth. 28688099 12 9 theme fetal 1863:1867 arg1 weight 1869:1874 fetal weight 1863:1874 fetal weight 1863:1874 TNF-α and IL-6 demonstrated positive correlations with placental weight and negative correlations with fetal weight and placental efficiency. 28688099 11 10 theme hyperglycemic 1734:1746 arg1 conditions 1748:1757 hyperglycemic conditions 1734:1757 hyperglycemic conditions 1734:1757 Furthermore, placental weight was increased, whereas fetal weight was decreased under hyperglycemic conditions. 28688099 13 11 theme inflammatory 2082:2093 arg1 exacerbation 2104:2115 inflammatory cytokine exacerbation 2082:2115 inflammatory cytokine exacerbation 2082:2115 Therefore, under hyperglycemic conditions, a modulatory role of O-GlcNAc in NF-κB activity was demonstrated in the placenta, contributing to fetal and placental dysfunction due to inflammatory cytokine exacerbation. 28688099 7 12 theme hyperglycemic 1127:1139 arg1 group 1141:1145 the hyperglycemic group 1123:1145 the hyperglycemic group 1123:1145 However, nuclear translocation of p65 subunit, showing greater activation of NF-κB, was increased in the hyperglycemic group. 28688099 1 13 theme subunits 397:404 arg1 modifications 351:363 post-translational modifications 332:363 post-translational modifications of modulatory proteins or NF-κB subunits (non-canonical pathway) 332:428 Inflammation as a result of NF-κB activation may result from the classical (canonical) pathway, with disconnection of the IκB inhibitor and subsequent nuclear translocation or, alternatively, by post-translational modifications of modulatory proteins or NF-κB subunits (non-canonical pathway). 28688099 2 14 theme augmented 581:589 arg1 production 591:600 augmented production 581:600 augmented production of pro-inflammatory cytokines 581:630 We hypothesized that hyperglycemia-induced increased glycosylation with O-linked N-acetylglucosamine (O-GlcNAc) of NF-κB in placental tissue leads to augmented production of pro-inflammatory cytokines, culminating in placental dysfunction and fetal restriction growth. 28688099 1 15 theme non-canonical 407:419 arg1 subunits 397:404 NF-κB subunits 391:404 NF-κB subunits (non-canonical pathway) 391:428 Inflammation as a result of NF-κB activation may result from the classical (canonical) pathway, with disconnection of the IκB inhibitor and subsequent nuclear translocation or, alternatively, by post-translational modifications of modulatory proteins or NF-κB subunits (non-canonical pathway). 28688099 1 15 theme non-canonical 407:419 arg1 pathway 421:427 non-canonical pathway 407:427 non-canonical pathway 407:427 Inflammation as a result of NF-κB activation may result from the classical (canonical) pathway, with disconnection of the IκB inhibitor and subsequent nuclear translocation or, alternatively, by post-translational modifications of modulatory proteins or NF-κB subunits (non-canonical pathway). 28688099 7 16 theme greater 1077:1083 arg1 activation 1085:1094 greater activation 1077:1094 greater activation of NF-κB 1077:1103 However, nuclear translocation of p65 subunit, showing greater activation of NF-κB, was increased in the hyperglycemic group. 28688099 8 17 theme classical 1305:1313 arg1 activation 1321:1330 increased classical NF-κB activation 1295:1330 increased classical NF-κB activation 1295:1330 Reduced expression of IκB and increased expression of phosphorylated IκBSer32 were observed in the placenta from hyperglycemic rats, demonstrating increased classical NF-κB activation. 28688099 9 18 theme p65 1440:1442 arg1 subunit 1444:1450 p65 subunit 1440:1450 p65 subunit 1440:1450 Augmented modification of O-GlcNAc-modified proteins was found in the placenta from hyperglycemic rats and p65 subunit was a key O-GlcNAc target, as demonstrated by immunoprecipitation. 28688099 9 18 theme p65 1440:1442 arg1 target 1471:1476 a key O-GlcNAc target 1456:1476 a key O-GlcNAc target 1456:1476 Augmented modification of O-GlcNAc-modified proteins was found in the placenta from hyperglycemic rats and p65 subunit was a key O-GlcNAc target, as demonstrated by immunoprecipitation. 28688099 3 19 theme female 827:832 arg1 rats 841:844 female Wistar rats 827:844 female Wistar rats 827:844 Single injections of streptozotocin (40 mg/kg) or vehicle were used to induce hyperglycemia or normoglycemia, respectively, in female Wistar rats. 28688099 13 20 from role 1958:1961 arg1 activity 1984:1991 NF-κB activity 1978:1991 NF-κB activity 1978:1991 Therefore, under hyperglycemic conditions, a modulatory role of O-GlcNAc in NF-κB activity was demonstrated in the placenta, contributing to fetal and placental dysfunction due to inflammatory cytokine exacerbation. 28688099 2 21 with glycosylation 484:496 arg1 O-GlcNAc 533:540 O-GlcNAc 533:540 O-GlcNAc 533:540 We hypothesized that hyperglycemia-induced increased glycosylation with O-linked N-acetylglucosamine (O-GlcNAc) of NF-κB in placental tissue leads to augmented production of pro-inflammatory cytokines, culminating in placental dysfunction and fetal restriction growth. 28688099 2 21 with glycosylation 484:496 arg1 N-acetylglucosamine 512:530 O-linked N-acetylglucosamine 503:530 O-linked N-acetylglucosamine (O-GlcNAc) of NF-κB in placental tissue 503:570 We hypothesized that hyperglycemia-induced increased glycosylation with O-linked N-acetylglucosamine (O-GlcNAc) of NF-κB in placental tissue leads to augmented production of pro-inflammatory cytokines, culminating in placental dysfunction and fetal restriction growth. 28688099 12 22 theme negative 1836:1843 arg1 correlations 1845:1856 negative correlations 1836:1856 negative correlations with fetal weight and placental efficiency 1836:1899 TNF-α and IL-6 demonstrated positive correlations with placental weight and negative correlations with fetal weight and placental efficiency. 28688099 2 23 theme cytokines 622:630 arg1 production 591:600 augmented production 581:600 augmented production of pro-inflammatory cytokines 581:630 We hypothesized that hyperglycemia-induced increased glycosylation with O-linked N-acetylglucosamine (O-GlcNAc) of NF-κB in placental tissue leads to augmented production of pro-inflammatory cytokines, culminating in placental dysfunction and fetal restriction growth. 28688099 7 24 theme NF-κB 1099:1103 arg1 activation 1085:1094 greater activation 1077:1094 greater activation of NF-κB 1077:1103 However, nuclear translocation of p65 subunit, showing greater activation of NF-κB, was increased in the hyperglycemic group. 28688099 9 25 theme O-GlcNAc-modified 1359:1375 arg1 proteins 1377:1384 O-GlcNAc-modified proteins 1359:1384 O-GlcNAc-modified proteins 1359:1384 Augmented modification of O-GlcNAc-modified proteins was found in the placenta from hyperglycemic rats and p65 subunit was a key O-GlcNAc target, as demonstrated by immunoprecipitation. 28688099 7 26 theme p65 1056:1058 arg1 subunit 1060:1066 p65 subunit 1056:1066 p65 subunit 1056:1066 However, nuclear translocation of p65 subunit, showing greater activation of NF-κB, was increased in the hyperglycemic group. 28688099 2 27 theme NF-κB 546:550 arg1 O-GlcNAc 533:540 O-GlcNAc 533:540 O-GlcNAc 533:540 We hypothesized that hyperglycemia-induced increased glycosylation with O-linked N-acetylglucosamine (O-GlcNAc) of NF-κB in placental tissue leads to augmented production of pro-inflammatory cytokines, culminating in placental dysfunction and fetal restriction growth. 28688099 2 27 theme NF-κB 546:550 arg1 N-acetylglucosamine 512:530 O-linked N-acetylglucosamine 503:530 O-linked N-acetylglucosamine (O-GlcNAc) of NF-κB in placental tissue 503:570 We hypothesized that hyperglycemia-induced increased glycosylation with O-linked N-acetylglucosamine (O-GlcNAc) of NF-κB in placental tissue leads to augmented production of pro-inflammatory cytokines, culminating in placental dysfunction and fetal restriction growth. 28688099 0 28 theme Cytokine 75:82 arg1 Production 84:93 Augmented Cytokine Production 65:93 Augmented Cytokine Production 65:93 Increased O-Linked N-Acetylglucosamine Modification of NF-ΚB and Augmented Cytokine Production in the Placentas from Hyperglycemic Rats. 28688099 5 29 theme pregnancy 947:955 arg1 21 days 936:942 21 days 936:942 21 days of pregnancy 936:955 Placental tissue was collected at 21 days of pregnancy. 28688099 1 30 theme activation 171:180 arg1 result 155:160 a result 153:160 a result of NF-κB activation 153:180 Inflammation as a result of NF-κB activation may result from the classical (canonical) pathway, with disconnection of the IκB inhibitor and subsequent nuclear translocation or, alternatively, by post-translational modifications of modulatory proteins or NF-κB subunits (non-canonical pathway). 28688099 1 31 theme modulatory 368:377 arg1 proteins 379:386 modulatory proteins 368:386 modulatory proteins 368:386 Inflammation as a result of NF-κB activation may result from the classical (canonical) pathway, with disconnection of the IκB inhibitor and subsequent nuclear translocation or, alternatively, by post-translational modifications of modulatory proteins or NF-κB subunits (non-canonical pathway). 28688099 12 32 with correlations 1845:1856 arg1 weight 1825:1830 placental weight 1815:1830 placental weight 1815:1830 TNF-α and IL-6 demonstrated positive correlations with placental weight and negative correlations with fetal weight and placental efficiency. 28688099 12 32 with correlations 1845:1856 arg1 weight 1869:1874 fetal weight 1863:1874 fetal weight 1863:1874 TNF-α and IL-6 demonstrated positive correlations with placental weight and negative correlations with fetal weight and placental efficiency. 28688099 12 32 with correlations 1845:1856 arg1 efficiency 1890:1899 placental efficiency 1880:1899 placental efficiency 1880:1899 TNF-α and IL-6 demonstrated positive correlations with placental weight and negative correlations with fetal weight and placental efficiency. 28688099 2 33 theme placental 555:563 arg1 tissue 565:570 placental tissue 555:570 placental tissue 555:570 We hypothesized that hyperglycemia-induced increased glycosylation with O-linked N-acetylglucosamine (O-GlcNAc) of NF-κB in placental tissue leads to augmented production of pro-inflammatory cytokines, culminating in placental dysfunction and fetal restriction growth. 28688099 11 34 dep increased 1682:1690 arg1 whereas 1693:1699 whereas 1693:1699 whereas 1693:1699 Furthermore, placental weight was increased, whereas fetal weight was decreased under hyperglycemic conditions. 28688099 0 35 theme Hyperglycemic 117:129 arg1 Rats 131:134 Hyperglycemic Rats 117:134 Hyperglycemic Rats 117:134 Increased O-Linked N-Acetylglucosamine Modification of NF-ΚB and Augmented Cytokine Production in the Placentas from Hyperglycemic Rats. 28688099 9 36 theme hyperglycemic 1417:1429 arg1 rats 1431:1434 hyperglycemic rats 1417:1434 hyperglycemic rats 1417:1434 Augmented modification of O-GlcNAc-modified proteins was found in the placenta from hyperglycemic rats and p65 subunit was a key O-GlcNAc target, as demonstrated by immunoprecipitation. 28688099 12 37 theme positive 1788:1795 arg1 correlations 1797:1808 positive correlations 1788:1808 positive correlations with placental weight 1788:1830 TNF-α and IL-6 demonstrated positive correlations with placental weight and negative correlations with fetal weight and placental efficiency. 28688099 2 38 from N-acetylglucosamine 512:530 arg1 tissue 565:570 placental tissue 555:570 placental tissue 555:570 We hypothesized that hyperglycemia-induced increased glycosylation with O-linked N-acetylglucosamine (O-GlcNAc) of NF-κB in placental tissue leads to augmented production of pro-inflammatory cytokines, culminating in placental dysfunction and fetal restriction growth. 28688099 10 39 theme interleukin-6 1559:1571 arg1 expressions 1580:1590 Tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) expressions 1519:1590 Tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) expressions 1519:1590 Tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) expressions were increased in the placenta from hyperglycemic rats. 28688099 2 40 theme hyperglycemia-induced 452:472 arg1 glycosylation 484:496 hyperglycemia-induced increased glycosylation 452:496 hyperglycemia-induced increased glycosylation with O-linked N-acetylglucosamine (O-GlcNAc) of NF-κB in placental tissue 452:570 We hypothesized that hyperglycemia-induced increased glycosylation with O-linked N-acetylglucosamine (O-GlcNAc) of NF-κB in placental tissue leads to augmented production of pro-inflammatory cytokines, culminating in placental dysfunction and fetal restriction growth. 28688099 0 41 theme N-Acetylglucosamine 19:37 arg1 Modification 39:50 O-Linked N-Acetylglucosamine Modification 10:50 O-Linked N-Acetylglucosamine Modification of NF-ΚB and Augmented Cytokine Production 10:93 Increased O-Linked N-Acetylglucosamine Modification of NF-ΚB and Augmented Cytokine Production in the Placentas from Hyperglycemic Rats. 28688099 1 42 theme nuclear 288:294 arg1 translocation 296:308 subsequent nuclear translocation 277:308 subsequent nuclear translocation 277:308 Inflammation as a result of NF-κB activation may result from the classical (canonical) pathway, with disconnection of the IκB inhibitor and subsequent nuclear translocation or, alternatively, by post-translational modifications of modulatory proteins or NF-κB subunits (non-canonical pathway). 28688099 10 43 from rats 1642:1645 arg1 placenta 1614:1621 the placenta 1610:1621 the placenta from hyperglycemic rats 1610:1645 Tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) expressions were increased in the placenta from hyperglycemic rats. 28688099 12 44 with correlations 1797:1808 arg1 weight 1825:1830 placental weight 1815:1830 placental weight 1815:1830 TNF-α and IL-6 demonstrated positive correlations with placental weight and negative correlations with fetal weight and placental efficiency. 28688099 12 44 with correlations 1797:1808 arg1 weight 1869:1874 fetal weight 1863:1874 fetal weight 1863:1874 TNF-α and IL-6 demonstrated positive correlations with placental weight and negative correlations with fetal weight and placental efficiency. 28688099 12 44 with correlations 1797:1808 arg1 efficiency 1890:1899 placental efficiency 1880:1899 placental efficiency 1880:1899 TNF-α and IL-6 demonstrated positive correlations with placental weight and negative correlations with fetal weight and placental efficiency. 28688099 3 45 theme streptozotocin 721:734 arg1 injections 707:716 Single injections 700:716 Single injections of streptozotocin (40 mg/kg) or vehicle 700:756 Single injections of streptozotocin (40 mg/kg) or vehicle were used to induce hyperglycemia or normoglycemia, respectively, in female Wistar rats. 28688099 8 46 theme Reduced 1148:1154 arg1 expression 1156:1165 Reduced expression 1148:1165 Reduced expression of IκB 1148:1172 Reduced expression of IκB and increased expression of phosphorylated IκBSer32 were observed in the placenta from hyperglycemic rats, demonstrating increased classical NF-κB activation. 28688099 2 47 theme O-linked 503:510 arg1 O-GlcNAc 533:540 O-GlcNAc 533:540 O-GlcNAc 533:540 We hypothesized that hyperglycemia-induced increased glycosylation with O-linked N-acetylglucosamine (O-GlcNAc) of NF-κB in placental tissue leads to augmented production of pro-inflammatory cytokines, culminating in placental dysfunction and fetal restriction growth. 28688099 2 47 theme O-linked 503:510 arg1 N-acetylglucosamine 512:530 O-linked N-acetylglucosamine 503:530 O-linked N-acetylglucosamine (O-GlcNAc) of NF-κB in placental tissue 503:570 We hypothesized that hyperglycemia-induced increased glycosylation with O-linked N-acetylglucosamine (O-GlcNAc) of NF-κB in placental tissue leads to augmented production of pro-inflammatory cytokines, culminating in placental dysfunction and fetal restriction growth. 28688099 0 48 mod Modification 39:50 arg1 NF-ΚB 55:59 NF-ΚB 55:59 NF-ΚB 55:59 Increased O-Linked N-Acetylglucosamine Modification of NF-ΚB and Augmented Cytokine Production in the Placentas from Hyperglycemic Rats. 28688099 0 48 mod Modification 39:50 arg3 N-Acetylglucosamine 19:37 O-Linked N-Acetylglucosamine 10:37 O-Linked N-Acetylglucosamine Modification of NF-ΚB and Augmented Cytokine Production 10:93 Increased O-Linked N-Acetylglucosamine Modification of NF-ΚB and Augmented Cytokine Production in the Placentas from Hyperglycemic Rats. 28688099 0 48 mod Modification 39:50 arg1 Production 84:93 Augmented Cytokine Production 65:93 Augmented Cytokine Production 65:93 Increased O-Linked N-Acetylglucosamine Modification of NF-ΚB and Augmented Cytokine Production in the Placentas from Hyperglycemic Rats. 28688099 11 49 theme fetal 1701:1705 arg1 weight 1707:1712 fetal weight 1701:1712 fetal weight 1701:1712 Furthermore, placental weight was increased, whereas fetal weight was decreased under hyperglycemic conditions. 28688099 9 50 theme O-GlcNAc 1462:1469 arg1 subunit 1444:1450 p65 subunit 1440:1450 p65 subunit 1440:1450 Augmented modification of O-GlcNAc-modified proteins was found in the placenta from hyperglycemic rats and p65 subunit was a key O-GlcNAc target, as demonstrated by immunoprecipitation. 28688099 9 50 theme O-GlcNAc 1462:1469 arg1 target 1471:1476 a key O-GlcNAc target 1456:1476 a key O-GlcNAc target 1456:1476 Augmented modification of O-GlcNAc-modified proteins was found in the placenta from hyperglycemic rats and p65 subunit was a key O-GlcNAc target, as demonstrated by immunoprecipitation. 28688099 8 51 from rats 1275:1278 arg1 placenta 1247:1254 the placenta 1243:1254 the placenta from hyperglycemic rats 1243:1278 Reduced expression of IκB and increased expression of phosphorylated IκBSer32 were observed in the placenta from hyperglycemic rats, demonstrating increased classical NF-κB activation. 28688099 3 52 used used 763:766 arg2 injections 707:716 Single injections 700:716 Single injections of streptozotocin (40 mg/kg) or vehicle 700:756 Single injections of streptozotocin (40 mg/kg) or vehicle were used to induce hyperglycemia or normoglycemia, respectively, in female Wistar rats. 28688099 8 53 theme phosphorylated 1202:1215 arg1 IκBSer32 1217:1224 phosphorylated IκBSer32 1202:1224 phosphorylated IκBSer32 1202:1224 Reduced expression of IκB and increased expression of phosphorylated IκBSer32 were observed in the placenta from hyperglycemic rats, demonstrating increased classical NF-κB activation. 28688099 1 54 theme IκB 259:261 arg1 inhibitor 263:271 the IκB inhibitor 255:271 the IκB inhibitor 255:271 Inflammation as a result of NF-κB activation may result from the classical (canonical) pathway, with disconnection of the IκB inhibitor and subsequent nuclear translocation or, alternatively, by post-translational modifications of modulatory proteins or NF-κB subunits (non-canonical pathway). 28688099 6 55 theme Placental 958:966 arg1 expression 968:977 Placental expression 958:977 Placental expression of p65 subunit 958:992 Placental expression of p65 subunit was similar between groups. 28688099 9 56 located found 1390:1394 arg2 modification 1343:1354 Augmented modification 1333:1354 Augmented modification of O-GlcNAc-modified proteins 1333:1384 Augmented modification of O-GlcNAc-modified proteins was found in the placenta from hyperglycemic rats and p65 subunit was a key O-GlcNAc target, as demonstrated by immunoprecipitation. 28688099 9 56 located found 1390:1394 arg1 placenta 1403:1410 the placenta 1399:1410 the placenta from hyperglycemic rats 1399:1434 Augmented modification of O-GlcNAc-modified proteins was found in the placenta from hyperglycemic rats and p65 subunit was a key O-GlcNAc target, as demonstrated by immunoprecipitation. 28688099 8 57 theme NF-κB 1315:1319 arg1 activation 1321:1330 increased classical NF-κB activation 1295:1330 increased classical NF-κB activation 1295:1330 Reduced expression of IκB and increased expression of phosphorylated IκBSer32 were observed in the placenta from hyperglycemic rats, demonstrating increased classical NF-κB activation. 28688099 10 58 theme Tumor 1519:1523 arg1 TNF-α 1548:1552 TNF-α 1548:1552 TNF-α 1548:1552 Tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) expressions were increased in the placenta from hyperglycemic rats. 28688099 10 58 theme Tumor 1519:1523 arg1 factor-alpha 1534:1545 Tumor necrosis factor-alpha 1519:1545 Tumor necrosis factor-alpha (TNF-α) 1519:1553 Tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) expressions were increased in the placenta from hyperglycemic rats. 28688099 9 59 from rats 1431:1434 arg1 placenta 1403:1410 the placenta 1399:1410 the placenta from hyperglycemic rats 1399:1434 Augmented modification of O-GlcNAc-modified proteins was found in the placenta from hyperglycemic rats and p65 subunit was a key O-GlcNAc target, as demonstrated by immunoprecipitation. 28688099 2 60 theme fetal 674:678 arg1 growth 692:697 fetal restriction growth 674:697 fetal restriction growth 674:697 We hypothesized that hyperglycemia-induced increased glycosylation with O-linked N-acetylglucosamine (O-GlcNAc) of NF-κB in placental tissue leads to augmented production of pro-inflammatory cytokines, culminating in placental dysfunction and fetal restriction growth. 28688099 12 61 theme placental 1880:1888 arg1 efficiency 1890:1899 placental efficiency 1880:1899 placental efficiency 1880:1899 TNF-α and IL-6 demonstrated positive correlations with placental weight and negative correlations with fetal weight and placental efficiency. 28688099 11 62 theme placental 1661:1669 arg1 weight 1671:1676 placental weight 1661:1676 placental weight 1661:1676 Furthermore, placental weight was increased, whereas fetal weight was decreased under hyperglycemic conditions. 28688099 1 63 theme classical 202:210 arg1 pathway 224:230 the classical (canonical) pathway 198:230 the classical (canonical) pathway 198:230 Inflammation as a result of NF-κB activation may result from the classical (canonical) pathway, with disconnection of the IκB inhibitor and subsequent nuclear translocation or, alternatively, by post-translational modifications of modulatory proteins or NF-κB subunits (non-canonical pathway). 28688099 8 64 theme hyperglycemic 1261:1273 arg1 rats 1275:1278 hyperglycemic rats 1261:1278 hyperglycemic rats 1261:1278 Reduced expression of IκB and increased expression of phosphorylated IκBSer32 were observed in the placenta from hyperglycemic rats, demonstrating increased classical NF-κB activation. 28688099 13 65 theme cytokine 2095:2102 arg1 exacerbation 2104:2115 inflammatory cytokine exacerbation 2082:2115 inflammatory cytokine exacerbation 2082:2115 Therefore, under hyperglycemic conditions, a modulatory role of O-GlcNAc in NF-κB activity was demonstrated in the placenta, contributing to fetal and placental dysfunction due to inflammatory cytokine exacerbation. 28688099 5 66 theme Placental 902:910 arg1 tissue 912:917 Placental tissue 902:917 Placental tissue 902:917 Placental tissue was collected at 21 days of pregnancy. 28688099 9 67 theme Augmented 1333:1341 arg1 modification 1343:1354 Augmented modification 1333:1354 Augmented modification of O-GlcNAc-modified proteins 1333:1384 Augmented modification of O-GlcNAc-modified proteins was found in the placenta from hyperglycemic rats and p65 subunit was a key O-GlcNAc target, as demonstrated by immunoprecipitation. 28688099 8 68 theme increased 1295:1303 arg1 activation 1321:1330 increased classical NF-κB activation 1295:1330 increased classical NF-κB activation 1295:1330 Reduced expression of IκB and increased expression of phosphorylated IκBSer32 were observed in the placenta from hyperglycemic rats, demonstrating increased classical NF-κB activation. 28688099 0 69 from Rats 131:134 arg1 Placentas 102:110 the Placentas 98:110 the Placentas from Hyperglycemic Rats 98:134 Increased O-Linked N-Acetylglucosamine Modification of NF-ΚB and Augmented Cytokine Production in the Placentas from Hyperglycemic Rats. 28688099 13 70 theme fetal 2043:2047 arg1 dysfunction 2063:2073 fetal and placental dysfunction 2043:2073 fetal and placental dysfunction 2043:2073 Therefore, under hyperglycemic conditions, a modulatory role of O-GlcNAc in NF-κB activity was demonstrated in the placenta, contributing to fetal and placental dysfunction due to inflammatory cytokine exacerbation. 28688099 3 71 theme Wistar 834:839 arg1 rats 841:844 female Wistar rats 827:844 female Wistar rats 827:844 Single injections of streptozotocin (40 mg/kg) or vehicle were used to induce hyperglycemia or normoglycemia, respectively, in female Wistar rats. 28688099 2 72 theme pro-inflammatory 605:620 arg1 cytokines 622:630 pro-inflammatory cytokines 605:630 pro-inflammatory cytokines 605:630 We hypothesized that hyperglycemia-induced increased glycosylation with O-linked N-acetylglucosamine (O-GlcNAc) of NF-κB in placental tissue leads to augmented production of pro-inflammatory cytokines, culminating in placental dysfunction and fetal restriction growth. 28688099 13 73 theme placental 2053:2061 arg1 dysfunction 2063:2073 fetal and placental dysfunction 2043:2073 fetal and placental dysfunction 2043:2073 Therefore, under hyperglycemic conditions, a modulatory role of O-GlcNAc in NF-κB activity was demonstrated in the placenta, contributing to fetal and placental dysfunction due to inflammatory cytokine exacerbation. 28688099 0 74 theme Production 84:93 arg1 Modification 39:50 O-Linked N-Acetylglucosamine Modification 10:50 O-Linked N-Acetylglucosamine Modification of NF-ΚB and Augmented Cytokine Production 10:93 Increased O-Linked N-Acetylglucosamine Modification of NF-ΚB and Augmented Cytokine Production in the Placentas from Hyperglycemic Rats. 28688099 9 75 theme proteins 1377:1384 arg1 modification 1343:1354 Augmented modification 1333:1354 Augmented modification of O-GlcNAc-modified proteins 1333:1384 Augmented modification of O-GlcNAc-modified proteins was found in the placenta from hyperglycemic rats and p65 subunit was a key O-GlcNAc target, as demonstrated by immunoprecipitation. 28688099 7 76 theme subunit 1060:1066 arg1 translocation 1039:1051 nuclear translocation 1031:1051 nuclear translocation of p65 subunit, showing greater activation of NF-κB, 1031:1104 However, nuclear translocation of p65 subunit, showing greater activation of NF-κB, was increased in the hyperglycemic group. 28688099 1 77 theme post-translational 332:349 arg1 modifications 351:363 post-translational modifications 332:363 post-translational modifications of modulatory proteins or NF-κB subunits (non-canonical pathway) 332:428 Inflammation as a result of NF-κB activation may result from the classical (canonical) pathway, with disconnection of the IκB inhibitor and subsequent nuclear translocation or, alternatively, by post-translational modifications of modulatory proteins or NF-κB subunits (non-canonical pathway). 28688099 1 78 theme NF-κB 165:169 arg1 activation 171:180 NF-κB activation 165:180 NF-κB activation 165:180 Inflammation as a result of NF-κB activation may result from the classical (canonical) pathway, with disconnection of the IκB inhibitor and subsequent nuclear translocation or, alternatively, by post-translational modifications of modulatory proteins or NF-κB subunits (non-canonical pathway). 28688099 7 79 theme nuclear 1031:1037 arg1 translocation 1039:1051 nuclear translocation 1031:1051 nuclear translocation of p65 subunit, showing greater activation of NF-κB, 1031:1104 However, nuclear translocation of p65 subunit, showing greater activation of NF-κB, was increased in the hyperglycemic group. 28688099 12 80 theme placental 1815:1823 arg1 weight 1825:1830 placental weight 1815:1830 placental weight 1815:1830 TNF-α and IL-6 demonstrated positive correlations with placental weight and negative correlations with fetal weight and placental efficiency. 28688099 10 81 theme factor-alpha 1534:1545 arg1 expressions 1580:1590 Tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) expressions 1519:1590 Tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) expressions 1519:1590 Tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) expressions were increased in the placenta from hyperglycemic rats. 28688099 1 82 theme proteins 379:386 arg1 modifications 351:363 post-translational modifications 332:363 post-translational modifications of modulatory proteins or NF-κB subunits (non-canonical pathway) 332:428 Inflammation as a result of NF-κB activation may result from the classical (canonical) pathway, with disconnection of the IκB inhibitor and subsequent nuclear translocation or, alternatively, by post-translational modifications of modulatory proteins or NF-κB subunits (non-canonical pathway). 28688099 2 83 link O-linked 503:510 arg1 O-GlcNAc 533:540 O-GlcNAc 533:540 O-GlcNAc 533:540 We hypothesized that hyperglycemia-induced increased glycosylation with O-linked N-acetylglucosamine (O-GlcNAc) of NF-κB in placental tissue leads to augmented production of pro-inflammatory cytokines, culminating in placental dysfunction and fetal restriction growth. 28688099 2 83 link O-linked 503:510 arg1 N-acetylglucosamine 512:530 O-linked N-acetylglucosamine 503:530 O-linked N-acetylglucosamine (O-GlcNAc) of NF-κB in placental tissue 503:570 We hypothesized that hyperglycemia-induced increased glycosylation with O-linked N-acetylglucosamine (O-GlcNAc) of NF-κB in placental tissue leads to augmented production of pro-inflammatory cytokines, culminating in placental dysfunction and fetal restriction growth. 28688099 0 84 theme O-Linked 10:17 arg1 N-Acetylglucosamine 19:37 O-Linked N-Acetylglucosamine 10:37 O-Linked N-Acetylglucosamine Modification of NF-ΚB and Augmented Cytokine Production 10:93 Increased O-Linked N-Acetylglucosamine Modification of NF-ΚB and Augmented Cytokine Production in the Placentas from Hyperglycemic Rats. 28688099 1 85 theme NF-κB 391:395 arg1 subunits 397:404 NF-κB subunits 391:404 NF-κB subunits (non-canonical pathway) 391:428 Inflammation as a result of NF-κB activation may result from the classical (canonical) pathway, with disconnection of the IκB inhibitor and subsequent nuclear translocation or, alternatively, by post-translational modifications of modulatory proteins or NF-κB subunits (non-canonical pathway). 28688099 1 85 theme NF-κB 391:395 arg1 pathway 421:427 non-canonical pathway 407:427 non-canonical pathway 407:427 Inflammation as a result of NF-κB activation may result from the classical (canonical) pathway, with disconnection of the IκB inhibitor and subsequent nuclear translocation or, alternatively, by post-translational modifications of modulatory proteins or NF-κB subunits (non-canonical pathway). 28688099 2 86 theme increased 474:482 arg1 glycosylation 484:496 hyperglycemia-induced increased glycosylation 452:496 hyperglycemia-induced increased glycosylation with O-linked N-acetylglucosamine (O-GlcNAc) of NF-κB in placental tissue 452:570 We hypothesized that hyperglycemia-induced increased glycosylation with O-linked N-acetylglucosamine (O-GlcNAc) of NF-κB in placental tissue leads to augmented production of pro-inflammatory cytokines, culminating in placental dysfunction and fetal restriction growth. 28688099 8 87 located observed 1231:1238 arg2 expression 1188:1197 increased expression 1178:1197 increased expression of phosphorylated IκBSer32 1178:1224 Reduced expression of IκB and increased expression of phosphorylated IκBSer32 were observed in the placenta from hyperglycemic rats, demonstrating increased classical NF-κB activation. 28688099 8 87 located observed 1231:1238 arg1 placenta 1247:1254 the placenta 1243:1254 the placenta from hyperglycemic rats 1243:1278 Reduced expression of IκB and increased expression of phosphorylated IκBSer32 were observed in the placenta from hyperglycemic rats, demonstrating increased classical NF-κB activation. 28688099 8 87 located observed 1231:1238 arg2 expression 1156:1165 Reduced expression 1148:1165 Reduced expression of IκB 1148:1172 Reduced expression of IκB and increased expression of phosphorylated IκBSer32 were observed in the placenta from hyperglycemic rats, demonstrating increased classical NF-κB activation. 28688099 13 88 theme O-GlcNAc 1966:1973 arg1 role 1958:1961 a modulatory role 1945:1961 a modulatory role of O-GlcNAc in NF-κB activity 1945:1991 Therefore, under hyperglycemic conditions, a modulatory role of O-GlcNAc in NF-κB activity was demonstrated in the placenta, contributing to fetal and placental dysfunction due to inflammatory cytokine exacerbation. 28688099 1 89 theme subsequent 277:286 arg1 translocation 296:308 subsequent nuclear translocation 277:308 subsequent nuclear translocation 277:308 Inflammation as a result of NF-κB activation may result from the classical (canonical) pathway, with disconnection of the IκB inhibitor and subsequent nuclear translocation or, alternatively, by post-translational modifications of modulatory proteins or NF-κB subunits (non-canonical pathway). 28688099 13 90 theme NF-κB 1978:1982 arg1 activity 1984:1991 NF-κB activity 1978:1991 NF-κB activity 1978:1991 Therefore, under hyperglycemic conditions, a modulatory role of O-GlcNAc in NF-κB activity was demonstrated in the placenta, contributing to fetal and placental dysfunction due to inflammatory cytokine exacerbation. 28688099 0 91 theme NF-ΚB 55:59 arg1 Modification 39:50 O-Linked N-Acetylglucosamine Modification 10:50 O-Linked N-Acetylglucosamine Modification of NF-ΚB and Augmented Cytokine Production 10:93 Increased O-Linked N-Acetylglucosamine Modification of NF-ΚB and Augmented Cytokine Production in the Placentas from Hyperglycemic Rats. 28688099 1 92 theme canonical 213:221 arg1 pathway 224:230 the classical (canonical) pathway 198:230 the classical (canonical) pathway 198:230 Inflammation as a result of NF-κB activation may result from the classical (canonical) pathway, with disconnection of the IκB inhibitor and subsequent nuclear translocation or, alternatively, by post-translational modifications of modulatory proteins or NF-κB subunits (non-canonical pathway). 28688099 3 93 theme Single 700:705 arg1 injections 707:716 Single injections 700:716 Single injections of streptozotocin (40 mg/kg) or vehicle 700:756 Single injections of streptozotocin (40 mg/kg) or vehicle were used to induce hyperglycemia or normoglycemia, respectively, in female Wistar rats. 28688099 0 94 theme Augmented 65:73 arg1 Production 84:93 Augmented Cytokine Production 65:93 Augmented Cytokine Production 65:93 Increased O-Linked N-Acetylglucosamine Modification of NF-ΚB and Augmented Cytokine Production in the Placentas from Hyperglycemic Rats. 28688099 9 95 theme key 1458:1460 arg1 subunit 1444:1450 p65 subunit 1440:1450 p65 subunit 1440:1450 Augmented modification of O-GlcNAc-modified proteins was found in the placenta from hyperglycemic rats and p65 subunit was a key O-GlcNAc target, as demonstrated by immunoprecipitation. 28688099 9 95 theme key 1458:1460 arg1 target 1471:1476 a key O-GlcNAc target 1456:1476 a key O-GlcNAc target 1456:1476 Augmented modification of O-GlcNAc-modified proteins was found in the placenta from hyperglycemic rats and p65 subunit was a key O-GlcNAc target, as demonstrated by immunoprecipitation. 28688099 8 96 theme IκB 1170:1172 arg1 expression 1188:1197 increased expression 1178:1197 increased expression of phosphorylated IκBSer32 1178:1224 Reduced expression of IκB and increased expression of phosphorylated IκBSer32 were observed in the placenta from hyperglycemic rats, demonstrating increased classical NF-κB activation. 28688099 8 96 theme IκB 1170:1172 arg1 expression 1156:1165 Reduced expression 1148:1165 Reduced expression of IκB 1148:1172 Reduced expression of IκB and increased expression of phosphorylated IκBSer32 were observed in the placenta from hyperglycemic rats, demonstrating increased classical NF-κB activation. 28688099 6 97 theme subunit 986:992 arg1 expression 968:977 Placental expression 958:977 Placental expression of p65 subunit 958:992 Placental expression of p65 subunit was similar between groups. 28688099 8 98 theme increased 1178:1186 arg1 expression 1188:1197 increased expression 1178:1197 increased expression of phosphorylated IκBSer32 1178:1224 Reduced expression of IκB and increased expression of phosphorylated IκBSer32 were observed in the placenta from hyperglycemic rats, demonstrating increased classical NF-κB activation. 28688099 13 99 theme modulatory 1947:1956 arg1 role 1958:1961 a modulatory role 1945:1961 a modulatory role of O-GlcNAc in NF-κB activity 1945:1991 Therefore, under hyperglycemic conditions, a modulatory role of O-GlcNAc in NF-κB activity was demonstrated in the placenta, contributing to fetal and placental dysfunction due to inflammatory cytokine exacerbation. 29113801 3 0 theme mass 751:754 arg1 spectrometry 756:767 parallel reaction monitoring mass spectrometry 722:767 parallel reaction monitoring mass spectrometry 722:767 To assess the functionality and glycoprotein producing capacity of the chromosomally based OST, a combined Western blot and parallel reaction monitoring mass spectrometry approach was applied, with absolute quantification of glycoprotein. 29113801 5 1 gly glycoprotein 1078:1089 arg1 glycoprotein 1078:1089 total glycoprotein production 1072:1100 total glycoprotein production 1072:1100 Although the engineered strain produced less total recombinant protein, the glycosylation efficiency increased by 85%, and total glycoprotein production was enhanced by 17%. 29113801 3 2 gly glycoprotein 823:834 arg1 glycoprotein 823:834 glycoprotein 823:834 glycoprotein 823:834 To assess the functionality and glycoprotein producing capacity of the chromosomally based OST, a combined Western blot and parallel reaction monitoring mass spectrometry approach was applied, with absolute quantification of glycoprotein. 29113801 2 3 theme expression 534:543 arg1 vectors 545:551 expression vectors 534:551 expression vectors 534:551 By inserting a codon optimised Campylobacter oligosaccharyltransferase onto the E. coli chromosome, we created a glycoprotein platform strain, where the target glycoprotein, sugar synthesis and glycosyltransferase enzymes, can be inserted using expression vectors to produce the desired homogenous glycoform. 29113801 0 4 theme oligosaccharyl 88:101 arg1 pglB 115:118 the bacterial oligosaccharyl transferase pglB 74:118 the bacterial oligosaccharyl transferase pglB 74:118 Producing a glycosylating Escherichia coli cell factory: The placement of the bacterial oligosaccharyl transferase pglB onto the genome. 29113801 3 5 theme reaction 731:738 arg1 spectrometry 756:767 parallel reaction monitoring mass spectrometry 722:767 parallel reaction monitoring mass spectrometry 722:767 To assess the functionality and glycoprotein producing capacity of the chromosomally based OST, a combined Western blot and parallel reaction monitoring mass spectrometry approach was applied, with absolute quantification of glycoprotein. 29113801 0 6 theme bacterial 78:86 arg1 pglB 115:118 the bacterial oligosaccharyl transferase pglB 74:118 the bacterial oligosaccharyl transferase pglB 74:118 Producing a glycosylating Escherichia coli cell factory: The placement of the bacterial oligosaccharyl transferase pglB onto the genome. 29113801 3 7 theme parallel 722:729 arg1 spectrometry 756:767 parallel reaction monitoring mass spectrometry 722:767 parallel reaction monitoring mass spectrometry 722:767 To assess the functionality and glycoprotein producing capacity of the chromosomally based OST, a combined Western blot and parallel reaction monitoring mass spectrometry approach was applied, with absolute quantification of glycoprotein. 29113801 1 8 gly glycosylating 246:258 arg0 strain 260:265 an optimal glycosylating strain 235:265 an optimal glycosylating strain 235:265 Although Escherichia coli has been engineered to perform N-glycosylation of recombinant proteins, an optimal glycosylating strain has not been created. 29113801 5 9 theme total 1072:1076 arg1 production 1091:1100 total glycoprotein production 1072:1100 total glycoprotein production 1072:1100 Although the engineered strain produced less total recombinant protein, the glycosylation efficiency increased by 85%, and total glycoprotein production was enhanced by 17%. 29113801 0 10 theme pglB 115:118 arg1 placement 61:69 The placement 57:69 The placement of the bacterial oligosaccharyl transferase pglB onto the genome 57:134 Producing a glycosylating Escherichia coli cell factory: The placement of the bacterial oligosaccharyl transferase pglB onto the genome. 29113801 5 11 theme glycoprotein 1078:1089 arg1 production 1091:1100 total glycoprotein production 1072:1100 total glycoprotein production 1072:1100 Although the engineered strain produced less total recombinant protein, the glycosylation efficiency increased by 85%, and total glycoprotein production was enhanced by 17%. 29113801 5 12 theme engineered 962:971 arg1 strain 973:978 the engineered strain 958:978 the engineered strain 958:978 Although the engineered strain produced less total recombinant protein, the glycosylation efficiency increased by 85%, and total glycoprotein production was enhanced by 17%. 29113801 0 13 theme transferase 103:113 arg1 pglB 115:118 the bacterial oligosaccharyl transferase pglB 74:118 the bacterial oligosaccharyl transferase pglB 74:118 Producing a glycosylating Escherichia coli cell factory: The placement of the bacterial oligosaccharyl transferase pglB onto the genome. 29113801 3 14 theme spectrometry 756:767 arg1 approach 769:776 a combined Western blot and parallel reaction monitoring mass spectrometry approach 694:776 a combined Western blot and parallel reaction monitoring mass spectrometry approach 694:776 To assess the functionality and glycoprotein producing capacity of the chromosomally based OST, a combined Western blot and parallel reaction monitoring mass spectrometry approach was applied, with absolute quantification of glycoprotein. 29113801 1 15 gly N-glycosylation 194:208 arg1 proteins 225:232 recombinant proteins 213:232 recombinant proteins 213:232 Although Escherichia coli has been engineered to perform N-glycosylation of recombinant proteins, an optimal glycosylating strain has not been created. 29113801 2 16 theme platform 415:422 arg1 strain 424:429 a glycoprotein platform strain 400:429 a glycoprotein platform strain 400:429 By inserting a codon optimised Campylobacter oligosaccharyltransferase onto the E. coli chromosome, we created a glycoprotein platform strain, where the target glycoprotein, sugar synthesis and glycosyltransferase enzymes, can be inserted using expression vectors to produce the desired homogenous glycoform. 29113801 2 17 theme Campylobacter 320:332 arg1 oligosaccharyltransferase 334:358 a codon optimised Campylobacter oligosaccharyltransferase 302:358 a codon optimised Campylobacter oligosaccharyltransferase onto the E. coli chromosome 302:386 By inserting a codon optimised Campylobacter oligosaccharyltransferase onto the E. coli chromosome, we created a glycoprotein platform strain, where the target glycoprotein, sugar synthesis and glycosyltransferase enzymes, can be inserted using expression vectors to produce the desired homogenous glycoform. 29113801 2 18 theme glycoprotein 402:413 arg1 strain 424:429 a glycoprotein platform strain 400:429 a glycoprotein platform strain 400:429 By inserting a codon optimised Campylobacter oligosaccharyltransferase onto the E. coli chromosome, we created a glycoprotein platform strain, where the target glycoprotein, sugar synthesis and glycosyltransferase enzymes, can be inserted using expression vectors to produce the desired homogenous glycoform. 29113801 2 19 theme sugar 463:467 arg1 glycoprotein 449:460 the target glycoprotein 438:460 the target glycoprotein 438:460 By inserting a codon optimised Campylobacter oligosaccharyltransferase onto the E. coli chromosome, we created a glycoprotein platform strain, where the target glycoprotein, sugar synthesis and glycosyltransferase enzymes, can be inserted using expression vectors to produce the desired homogenous glycoform. 29113801 2 19 theme sugar 463:467 arg1 synthesis 469:477 sugar synthesis and glycosyltransferase enzymes 463:509 synthesis 469:477 By inserting a codon optimised Campylobacter oligosaccharyltransferase onto the E. coli chromosome, we created a glycoprotein platform strain, where the target glycoprotein, sugar synthesis and glycosyltransferase enzymes, can be inserted using expression vectors to produce the desired homogenous glycoform. 29113801 3 20 theme absolute 796:803 arg1 quantification 805:818 absolute quantification 796:818 absolute quantification of glycoprotein 796:834 To assess the functionality and glycoprotein producing capacity of the chromosomally based OST, a combined Western blot and parallel reaction monitoring mass spectrometry approach was applied, with absolute quantification of glycoprotein. 29113801 2 21 gly glycoprotein 402:413 arg1 glycoprotein 402:413 a glycoprotein platform strain 400:429 a glycoprotein platform strain 400:429 By inserting a codon optimised Campylobacter oligosaccharyltransferase onto the E. coli chromosome, we created a glycoprotein platform strain, where the target glycoprotein, sugar synthesis and glycosyltransferase enzymes, can be inserted using expression vectors to produce the desired homogenous glycoform. 29113801 2 22 theme optimised 310:318 arg1 oligosaccharyltransferase 334:358 a codon optimised Campylobacter oligosaccharyltransferase 302:358 a codon optimised Campylobacter oligosaccharyltransferase onto the E. coli chromosome 302:386 By inserting a codon optimised Campylobacter oligosaccharyltransferase onto the E. coli chromosome, we created a glycoprotein platform strain, where the target glycoprotein, sugar synthesis and glycosyltransferase enzymes, can be inserted using expression vectors to produce the desired homogenous glycoform. 29113801 0 23 theme Escherichia 26:36 arg1 factory 48:54 a glycosylating Escherichia coli cell factory 10:54 a glycosylating Escherichia coli cell factory 10:54 Producing a glycosylating Escherichia coli cell factory: The placement of the bacterial oligosaccharyl transferase pglB onto the genome. 29113801 2 24 theme codon 304:308 arg1 oligosaccharyltransferase 334:358 a codon optimised Campylobacter oligosaccharyltransferase 302:358 a codon optimised Campylobacter oligosaccharyltransferase onto the E. coli chromosome 302:386 By inserting a codon optimised Campylobacter oligosaccharyltransferase onto the E. coli chromosome, we created a glycoprotein platform strain, where the target glycoprotein, sugar synthesis and glycosyltransferase enzymes, can be inserted using expression vectors to produce the desired homogenous glycoform. 29113801 2 25 theme target 442:447 arg1 glycoprotein 449:460 the target glycoprotein 438:460 the target glycoprotein 438:460 By inserting a codon optimised Campylobacter oligosaccharyltransferase onto the E. coli chromosome, we created a glycoprotein platform strain, where the target glycoprotein, sugar synthesis and glycosyltransferase enzymes, can be inserted using expression vectors to produce the desired homogenous glycoform. 29113801 2 25 theme target 442:447 arg1 synthesis 469:477 sugar synthesis and glycosyltransferase enzymes 463:509 synthesis 469:477 By inserting a codon optimised Campylobacter oligosaccharyltransferase onto the E. coli chromosome, we created a glycoprotein platform strain, where the target glycoprotein, sugar synthesis and glycosyltransferase enzymes, can be inserted using expression vectors to produce the desired homogenous glycoform. 29113801 2 25 theme target 442:447 arg1 enzymes 503:509 sugar synthesis and glycosyltransferase enzymes 463:509 enzymes 503:509 By inserting a codon optimised Campylobacter oligosaccharyltransferase onto the E. coli chromosome, we created a glycoprotein platform strain, where the target glycoprotein, sugar synthesis and glycosyltransferase enzymes, can be inserted using expression vectors to produce the desired homogenous glycoform. 29113801 0 26 theme glycosylating 12:24 arg1 factory 48:54 a glycosylating Escherichia coli cell factory 10:54 a glycosylating Escherichia coli cell factory 10:54 Producing a glycosylating Escherichia coli cell factory: The placement of the bacterial oligosaccharyl transferase pglB onto the genome. 29113801 2 27 theme homogenous 576:585 arg1 glycoform 587:595 the desired homogenous glycoform 564:595 the desired homogenous glycoform 564:595 By inserting a codon optimised Campylobacter oligosaccharyltransferase onto the E. coli chromosome, we created a glycoprotein platform strain, where the target glycoprotein, sugar synthesis and glycosyltransferase enzymes, can be inserted using expression vectors to produce the desired homogenous glycoform. 29113801 3 28 gly glycoprotein 630:641 arg1 glycoprotein 630:641 glycoprotein producing capacity 630:660 glycoprotein producing capacity 630:660 To assess the functionality and glycoprotein producing capacity of the chromosomally based OST, a combined Western blot and parallel reaction monitoring mass spectrometry approach was applied, with absolute quantification of glycoprotein. 29113801 0 29 theme cell 43:46 arg1 factory 48:54 a glycosylating Escherichia coli cell factory 10:54 a glycosylating Escherichia coli cell factory 10:54 Producing a glycosylating Escherichia coli cell factory: The placement of the bacterial oligosaccharyl transferase pglB onto the genome. 29113801 2 30 theme desired 568:574 arg1 glycoform 587:595 the desired homogenous glycoform 564:595 the desired homogenous glycoform 564:595 By inserting a codon optimised Campylobacter oligosaccharyltransferase onto the E. coli chromosome, we created a glycoprotein platform strain, where the target glycoprotein, sugar synthesis and glycosyltransferase enzymes, can be inserted using expression vectors to produce the desired homogenous glycoform. 29113801 3 31 theme glycoprotein 630:641 arg1 capacity 653:660 glycoprotein producing capacity 630:660 glycoprotein producing capacity 630:660 To assess the functionality and glycoprotein producing capacity of the chromosomally based OST, a combined Western blot and parallel reaction monitoring mass spectrometry approach was applied, with absolute quantification of glycoprotein. 29113801 1 32 theme recombinant 213:223 arg1 proteins 225:232 recombinant proteins 213:232 recombinant proteins 213:232 Although Escherichia coli has been engineered to perform N-glycosylation of recombinant proteins, an optimal glycosylating strain has not been created. 29113801 3 33 theme based 683:687 arg1 OST 689:691 the chromosomally based OST 665:691 the chromosomally based OST 665:691 To assess the functionality and glycoprotein producing capacity of the chromosomally based OST, a combined Western blot and parallel reaction monitoring mass spectrometry approach was applied, with absolute quantification of glycoprotein. 29113801 3 34 theme producing 643:651 arg1 capacity 653:660 glycoprotein producing capacity 630:660 glycoprotein producing capacity 630:660 To assess the functionality and glycoprotein producing capacity of the chromosomally based OST, a combined Western blot and parallel reaction monitoring mass spectrometry approach was applied, with absolute quantification of glycoprotein. 29113801 1 35 theme proteins 225:232 arg1 N-glycosylation 194:208 N-glycosylation 194:208 N-glycosylation of recombinant proteins 194:232 Although Escherichia coli has been engineered to perform N-glycosylation of recombinant proteins, an optimal glycosylating strain has not been created. 29113801 2 36 theme glycosyltransferase 483:501 arg1 glycoprotein 449:460 the target glycoprotein 438:460 the target glycoprotein 438:460 By inserting a codon optimised Campylobacter oligosaccharyltransferase onto the E. coli chromosome, we created a glycoprotein platform strain, where the target glycoprotein, sugar synthesis and glycosyltransferase enzymes, can be inserted using expression vectors to produce the desired homogenous glycoform. 29113801 2 36 theme glycosyltransferase 483:501 arg1 enzymes 503:509 sugar synthesis and glycosyltransferase enzymes 463:509 enzymes 503:509 By inserting a codon optimised Campylobacter oligosaccharyltransferase onto the E. coli chromosome, we created a glycoprotein platform strain, where the target glycoprotein, sugar synthesis and glycosyltransferase enzymes, can be inserted using expression vectors to produce the desired homogenous glycoform. 29113801 3 37 theme OST 689:691 arg1 functionality 612:624 the functionality 608:624 the functionality 608:624 To assess the functionality and glycoprotein producing capacity of the chromosomally based OST, a combined Western blot and parallel reaction monitoring mass spectrometry approach was applied, with absolute quantification of glycoprotein. 29113801 3 37 theme OST 689:691 arg1 capacity 653:660 glycoprotein producing capacity 630:660 glycoprotein producing capacity 630:660 To assess the functionality and glycoprotein producing capacity of the chromosomally based OST, a combined Western blot and parallel reaction monitoring mass spectrometry approach was applied, with absolute quantification of glycoprotein. 29113801 0 38 gly glycosylating 12:24 arg0 factory 48:54 a glycosylating Escherichia coli cell factory 10:54 a glycosylating Escherichia coli cell factory 10:54 Producing a glycosylating Escherichia coli cell factory: The placement of the bacterial oligosaccharyl transferase pglB onto the genome. 29113801 2 39 theme E. coli 369:375 arg1 chromosome 377:386 the E. coli chromosome 365:386 the E. coli chromosome 365:386 By inserting a codon optimised Campylobacter oligosaccharyltransferase onto the E. coli chromosome, we created a glycoprotein platform strain, where the target glycoprotein, sugar synthesis and glycosyltransferase enzymes, can be inserted using expression vectors to produce the desired homogenous glycoform. 29113801 3 40 theme blot 713:716 arg1 approach 769:776 a combined Western blot and parallel reaction monitoring mass spectrometry approach 694:776 a combined Western blot and parallel reaction monitoring mass spectrometry approach 694:776 To assess the functionality and glycoprotein producing capacity of the chromosomally based OST, a combined Western blot and parallel reaction monitoring mass spectrometry approach was applied, with absolute quantification of glycoprotein. 29113801 5 41 theme glycosylation 1025:1037 arg1 efficiency 1039:1048 the glycosylation efficiency 1021:1048 the glycosylation efficiency 1021:1048 Although the engineered strain produced less total recombinant protein, the glycosylation efficiency increased by 85%, and total glycoprotein production was enhanced by 17%. 29113801 4 42 theme chromosomal 858:868 arg1 oligosaccharyltransferase 870:894 chromosomal oligosaccharyltransferase 858:894 chromosomal oligosaccharyltransferase 858:894 We demonstrated that chromosomal oligosaccharyltransferase remained functional and facilitated N-glycosylation. 29113801 3 43 theme glycoprotein 823:834 arg1 quantification 805:818 absolute quantification 796:818 absolute quantification of glycoprotein 796:834 To assess the functionality and glycoprotein producing capacity of the chromosomally based OST, a combined Western blot and parallel reaction monitoring mass spectrometry approach was applied, with absolute quantification of glycoprotein. 29113801 0 44 dep Escherichia 26:36 arg1 coli 38:41 coli 38:41 coli 38:41 Producing a glycosylating Escherichia coli cell factory: The placement of the bacterial oligosaccharyl transferase pglB onto the genome. 29113801 3 45 theme combined 696:703 arg1 blot 713:716 combined Western blot 696:716 combined Western blot 696:716 To assess the functionality and glycoprotein producing capacity of the chromosomally based OST, a combined Western blot and parallel reaction monitoring mass spectrometry approach was applied, with absolute quantification of glycoprotein. 29113801 3 46 theme Western 705:711 arg1 blot 713:716 combined Western blot 696:716 combined Western blot 696:716 To assess the functionality and glycoprotein producing capacity of the chromosomally based OST, a combined Western blot and parallel reaction monitoring mass spectrometry approach was applied, with absolute quantification of glycoprotein. 29113801 2 47 gly glycoprotein 449:460 arg1 glycoprotein 449:460 the target glycoprotein 438:460 the target glycoprotein 438:460 By inserting a codon optimised Campylobacter oligosaccharyltransferase onto the E. coli chromosome, we created a glycoprotein platform strain, where the target glycoprotein, sugar synthesis and glycosyltransferase enzymes, can be inserted using expression vectors to produce the desired homogenous glycoform. 29113801 2 47 gly glycoprotein 449:460 arg1 synthesis 469:477 sugar synthesis and glycosyltransferase enzymes 463:509 synthesis 469:477 By inserting a codon optimised Campylobacter oligosaccharyltransferase onto the E. coli chromosome, we created a glycoprotein platform strain, where the target glycoprotein, sugar synthesis and glycosyltransferase enzymes, can be inserted using expression vectors to produce the desired homogenous glycoform. 29113801 2 47 gly glycoprotein 449:460 arg1 enzymes 503:509 sugar synthesis and glycosyltransferase enzymes 463:509 enzymes 503:509 By inserting a codon optimised Campylobacter oligosaccharyltransferase onto the E. coli chromosome, we created a glycoprotein platform strain, where the target glycoprotein, sugar synthesis and glycosyltransferase enzymes, can be inserted using expression vectors to produce the desired homogenous glycoform. 29113801 5 48 theme total 994:998 arg1 protein 1012:1018 total recombinant protein 994:1018 less total recombinant protein 989:1018 Although the engineered strain produced less total recombinant protein, the glycosylation efficiency increased by 85%, and total glycoprotein production was enhanced by 17%. 29113801 1 49 theme optimal 238:244 arg1 strain 260:265 an optimal glycosylating strain 235:265 an optimal glycosylating strain 235:265 Although Escherichia coli has been engineered to perform N-glycosylation of recombinant proteins, an optimal glycosylating strain has not been created. 29113801 3 50 theme monitoring 740:749 arg1 spectrometry 756:767 parallel reaction monitoring mass spectrometry 722:767 parallel reaction monitoring mass spectrometry 722:767 To assess the functionality and glycoprotein producing capacity of the chromosomally based OST, a combined Western blot and parallel reaction monitoring mass spectrometry approach was applied, with absolute quantification of glycoprotein. 29113801 0 51 dep Producing 0:8 arg1 placement 61:69 The placement 57:69 The placement of the bacterial oligosaccharyl transferase pglB onto the genome 57:134 Producing a glycosylating Escherichia coli cell factory: The placement of the bacterial oligosaccharyl transferase pglB onto the genome. 29113801 5 52 theme recombinant 1000:1010 arg1 protein 1012:1018 total recombinant protein 994:1018 less total recombinant protein 989:1018 Although the engineered strain produced less total recombinant protein, the glycosylation efficiency increased by 85%, and total glycoprotein production was enhanced by 17%. 29113801 1 53 theme glycosylating 246:258 arg1 strain 260:265 an optimal glycosylating strain 235:265 an optimal glycosylating strain 235:265 Although Escherichia coli has been engineered to perform N-glycosylation of recombinant proteins, an optimal glycosylating strain has not been created. 28808994 4 0 theme surface 613:619 arg1 presentation 629:640 cell surface protein presentation 608:640 cell surface protein presentation 608:640 Precise and multiplexed quantification of relative changes of cell surface protein presentation is enabled by an isobaric labeling strategy. 28808994 4 1 theme presentation 629:640 arg1 changes 597:603 relative changes 588:603 relative changes of cell surface protein presentation 588:640 Precise and multiplexed quantification of relative changes of cell surface protein presentation is enabled by an isobaric labeling strategy. 28808994 4 2 theme protein 621:627 arg1 presentation 629:640 cell surface protein presentation 608:640 cell surface protein presentation 608:640 Precise and multiplexed quantification of relative changes of cell surface protein presentation is enabled by an isobaric labeling strategy. 28808994 2 3 dep identification 324:337 arg1 the 311:313 the 311:313 the 311:313 Cell surface labeling in combination with quantitative proteomics enables the unbiased identification and quantification of cell surface proteins. 28808994 2 4 theme unbiased 315:322 arg1 identification 324:337 unbiased identification 315:337 unbiased identification 315:337 Cell surface labeling in combination with quantitative proteomics enables the unbiased identification and quantification of cell surface proteins. 28808994 3 5 theme fast 398:401 arg1 protocol 426:433 a fast, efficient, and robust protocol 396:433 a fast, efficient, and robust protocol for the enrichment of the N-linked plasma membrane glycoproteome 396:498 We describe a fast, efficient, and robust protocol for the enrichment of the N-linked plasma membrane glycoproteome and subsequent analysis by mass spectrometry. 28808994 1 6 theme proteome 133:140 arg1 analysis 93:100 The analysis 89:100 The analysis of the cell surface accessible proteome 89:140 The analysis of the cell surface accessible proteome provides invaluable information about cellular identity, cellular functions, and interactions. 28808994 1 7 theme cellular 180:187 arg1 identity 189:196 cellular identity 180:196 cellular identity 180:196 The analysis of the cell surface accessible proteome provides invaluable information about cellular identity, cellular functions, and interactions. 28808994 2 8 from labeling 250:257 arg1 combination 262:272 combination 262:272 combination 262:272 Cell surface labeling in combination with quantitative proteomics enables the unbiased identification and quantification of cell surface proteins. 28808994 3 9 theme N-linked 461:468 arg1 glycoproteome 486:498 the N-linked plasma membrane glycoproteome 457:498 the N-linked plasma membrane glycoproteome 457:498 We describe a fast, efficient, and robust protocol for the enrichment of the N-linked plasma membrane glycoproteome and subsequent analysis by mass spectrometry. 28808994 0 10 theme Dynamic 11:17 arg1 Changes 19:25 Dynamic Changes 11:25 Dynamic Changes of the Cell Surface Glycoproteome 11:59 Monitoring Dynamic Changes of the Cell Surface Glycoproteome by Quantitative Proteomics. 28808994 4 11 theme cell 608:611 arg1 presentation 629:640 cell surface protein presentation 608:640 cell surface protein presentation 608:640 Precise and multiplexed quantification of relative changes of cell surface protein presentation is enabled by an isobaric labeling strategy. 28808994 3 12 link N-linked 461:468 arg1 glycoproteome 486:498 the N-linked plasma membrane glycoproteome 457:498 the N-linked plasma membrane glycoproteome 457:498 We describe a fast, efficient, and robust protocol for the enrichment of the N-linked plasma membrane glycoproteome and subsequent analysis by mass spectrometry. 28808994 1 13 theme cellular 199:206 arg1 functions 208:216 cellular functions 199:216 cellular functions 199:216 The analysis of the cell surface accessible proteome provides invaluable information about cellular identity, cellular functions, and interactions. 28808994 4 14 theme changes 597:603 arg1 quantification 570:583 Precise and multiplexed quantification 546:583 Precise and multiplexed quantification of relative changes of cell surface protein presentation 546:640 Precise and multiplexed quantification of relative changes of cell surface protein presentation is enabled by an isobaric labeling strategy. 28808994 3 15 theme glycoproteome 486:498 arg1 enrichment 443:452 the enrichment 439:452 the enrichment of the N-linked plasma membrane glycoproteome 439:498 We describe a fast, efficient, and robust protocol for the enrichment of the N-linked plasma membrane glycoproteome and subsequent analysis by mass spectrometry. 28808994 3 16 theme efficient 404:412 arg1 protocol 426:433 a fast, efficient, and robust protocol 396:433 a fast, efficient, and robust protocol for the enrichment of the N-linked plasma membrane glycoproteome 396:498 We describe a fast, efficient, and robust protocol for the enrichment of the N-linked plasma membrane glycoproteome and subsequent analysis by mass spectrometry. 28808994 2 17 with labeling 250:257 arg1 proteomics 292:301 quantitative proteomics 279:301 quantitative proteomics 279:301 Cell surface labeling in combination with quantitative proteomics enables the unbiased identification and quantification of cell surface proteins. 28808994 3 18 theme mass 527:530 arg1 spectrometry 532:543 mass spectrometry 527:543 mass spectrometry 527:543 We describe a fast, efficient, and robust protocol for the enrichment of the N-linked plasma membrane glycoproteome and subsequent analysis by mass spectrometry. 28808994 0 19 theme Cell 34:37 arg1 Glycoproteome 47:59 the Cell Surface Glycoproteome 30:59 the Cell Surface Glycoproteome 30:59 Monitoring Dynamic Changes of the Cell Surface Glycoproteome by Quantitative Proteomics. 28808994 2 20 theme proteins 374:381 arg1 quantification 343:356 quantification 343:356 quantification 343:356 Cell surface labeling in combination with quantitative proteomics enables the unbiased identification and quantification of cell surface proteins. 28808994 2 20 theme proteins 374:381 arg1 identification 324:337 unbiased identification 315:337 unbiased identification 315:337 Cell surface labeling in combination with quantitative proteomics enables the unbiased identification and quantification of cell surface proteins. 28808994 3 21 theme plasma 470:475 arg1 glycoproteome 486:498 the N-linked plasma membrane glycoproteome 457:498 the N-linked plasma membrane glycoproteome 457:498 We describe a fast, efficient, and robust protocol for the enrichment of the N-linked plasma membrane glycoproteome and subsequent analysis by mass spectrometry. 28808994 2 22 theme surface 242:248 arg1 labeling 250:257 Cell surface labeling 237:257 Cell surface labeling in combination with quantitative proteomics 237:301 Cell surface labeling in combination with quantitative proteomics enables the unbiased identification and quantification of cell surface proteins. 28808994 3 23 theme membrane 477:484 arg1 glycoproteome 486:498 the N-linked plasma membrane glycoproteome 457:498 the N-linked plasma membrane glycoproteome 457:498 We describe a fast, efficient, and robust protocol for the enrichment of the N-linked plasma membrane glycoproteome and subsequent analysis by mass spectrometry. 28808994 0 24 theme Glycoproteome 47:59 arg1 Changes 19:25 Dynamic Changes 11:25 Dynamic Changes of the Cell Surface Glycoproteome 11:59 Monitoring Dynamic Changes of the Cell Surface Glycoproteome by Quantitative Proteomics. 28808994 4 25 theme multiplexed 558:568 arg1 quantification 570:583 Precise and multiplexed quantification 546:583 Precise and multiplexed quantification of relative changes of cell surface protein presentation 546:640 Precise and multiplexed quantification of relative changes of cell surface protein presentation is enabled by an isobaric labeling strategy. 28808994 2 26 theme Cell 237:240 arg1 labeling 250:257 Cell surface labeling 237:257 Cell surface labeling in combination with quantitative proteomics 237:301 Cell surface labeling in combination with quantitative proteomics enables the unbiased identification and quantification of cell surface proteins. 28808994 1 27 theme cell 109:112 arg1 proteome 133:140 the cell surface accessible proteome 105:140 the cell surface accessible proteome 105:140 The analysis of the cell surface accessible proteome provides invaluable information about cellular identity, cellular functions, and interactions. 28808994 0 28 theme Surface 39:45 arg1 Glycoproteome 47:59 the Cell Surface Glycoproteome 30:59 the Cell Surface Glycoproteome 30:59 Monitoring Dynamic Changes of the Cell Surface Glycoproteome by Quantitative Proteomics. 28808994 4 29 theme relative 588:595 arg1 changes 597:603 relative changes 588:603 relative changes of cell surface protein presentation 588:640 Precise and multiplexed quantification of relative changes of cell surface protein presentation is enabled by an isobaric labeling strategy. 28808994 3 30 theme subsequent 504:513 arg1 analysis 515:522 subsequent analysis 504:522 subsequent analysis by mass spectrometry 504:543 We describe a fast, efficient, and robust protocol for the enrichment of the N-linked plasma membrane glycoproteome and subsequent analysis by mass spectrometry. 28808994 1 31 theme surface 114:120 arg1 proteome 133:140 the cell surface accessible proteome 105:140 the cell surface accessible proteome 105:140 The analysis of the cell surface accessible proteome provides invaluable information about cellular identity, cellular functions, and interactions. 28808994 2 32 theme quantitative 279:290 arg1 proteomics 292:301 quantitative proteomics 279:301 quantitative proteomics 279:301 Cell surface labeling in combination with quantitative proteomics enables the unbiased identification and quantification of cell surface proteins. 28808994 1 33 theme accessible 122:131 arg1 proteome 133:140 the cell surface accessible proteome 105:140 the cell surface accessible proteome 105:140 The analysis of the cell surface accessible proteome provides invaluable information about cellular identity, cellular functions, and interactions. 28808994 4 34 theme Precise 546:552 arg1 quantification 570:583 Precise and multiplexed quantification 546:583 Precise and multiplexed quantification of relative changes of cell surface protein presentation 546:640 Precise and multiplexed quantification of relative changes of cell surface protein presentation is enabled by an isobaric labeling strategy. 28808994 2 35 theme cell 361:364 arg1 proteins 374:381 cell surface proteins 361:381 cell surface proteins 361:381 Cell surface labeling in combination with quantitative proteomics enables the unbiased identification and quantification of cell surface proteins. 28808994 2 36 theme surface 366:372 arg1 proteins 374:381 cell surface proteins 361:381 cell surface proteins 361:381 Cell surface labeling in combination with quantitative proteomics enables the unbiased identification and quantification of cell surface proteins. 28808994 0 37 theme Quantitative 64:75 arg1 Proteomics 77:86 Quantitative Proteomics 64:86 Quantitative Proteomics 64:86 Monitoring Dynamic Changes of the Cell Surface Glycoproteome by Quantitative Proteomics. 28808994 4 38 theme labeling 668:675 arg1 strategy 677:684 an isobaric labeling strategy 656:684 an isobaric labeling strategy 656:684 Precise and multiplexed quantification of relative changes of cell surface protein presentation is enabled by an isobaric labeling strategy. 28808994 3 39 theme robust 419:424 arg1 protocol 426:433 a fast, efficient, and robust protocol 396:433 a fast, efficient, and robust protocol for the enrichment of the N-linked plasma membrane glycoproteome 396:498 We describe a fast, efficient, and robust protocol for the enrichment of the N-linked plasma membrane glycoproteome and subsequent analysis by mass spectrometry. 28808994 1 40 theme invaluable 151:160 arg1 information 162:172 invaluable information 151:172 invaluable information about cellular identity, cellular functions, and interactions 151:234 The analysis of the cell surface accessible proteome provides invaluable information about cellular identity, cellular functions, and interactions. 28808994 4 41 theme isobaric 659:666 arg1 strategy 677:684 an isobaric labeling strategy 656:684 an isobaric labeling strategy 656:684 Precise and multiplexed quantification of relative changes of cell surface protein presentation is enabled by an isobaric labeling strategy. 25805188 1 0 theme nanoporous 154:163 arg1 NPC 173:175 NPC 173:175 NPC 173:175 In this work, magnetic nanoporous carbon (NPC) materials were synthesized by choosing a MOF as a sacrificial template and a carbon precursor. 25805188 1 0 theme nanoporous 154:163 arg1 carbon 165:170 magnetic nanoporous carbon 145:170 magnetic nanoporous carbon (NPC) materials 145:186 In this work, magnetic nanoporous carbon (NPC) materials were synthesized by choosing a MOF as a sacrificial template and a carbon precursor. 25805188 1 1 theme sacrificial 228:238 arg1 template 240:247 a sacrificial template 226:247 a sacrificial template 226:247 In this work, magnetic nanoporous carbon (NPC) materials were synthesized by choosing a MOF as a sacrificial template and a carbon precursor. 25805188 1 1 theme sacrificial 228:238 arg1 MOF 219:221 a MOF 217:221 a MOF 217:221 In this work, magnetic nanoporous carbon (NPC) materials were synthesized by choosing a MOF as a sacrificial template and a carbon precursor. 25805188 0 2 link MOF-derived 22:32 arg1 materials 61:69 MOF-derived magnetic nanoporous carbon materials 22:69 MOF-derived magnetic nanoporous carbon materials 22:69 Designed synthesis of MOF-derived magnetic nanoporous carbon materials for selective enrichment of glycans for glycomics analysis. 25805188 1 3 theme carbon 165:170 arg1 materials 178:186 magnetic nanoporous carbon (NPC) materials 145:186 magnetic nanoporous carbon (NPC) materials 145:186 In this work, magnetic nanoporous carbon (NPC) materials were synthesized by choosing a MOF as a sacrificial template and a carbon precursor. 25805188 3 4 theme high 533:536 arg1 selectivity 538:548 high selectivity 533:548 high selectivity 533:548 The Co-ZIF-67 materials were successfully applied to glycomics analysis by enriching N-linked glycans in bio-samples with high selectivity and efficiency. 25805188 2 5 theme obtained 277:284 arg1 materials 296:304 The obtained Co-ZIF-67 materials 273:304 The obtained Co-ZIF-67 materials 273:304 The obtained Co-ZIF-67 materials showed strong magnetic response, high surface area, a uniform size of mesopores and high carbon content. 25805188 0 6 theme glycans 99:105 arg1 enrichment 85:94 selective enrichment 75:94 selective enrichment of glycans for glycomics analysis 75:128 Designed synthesis of MOF-derived magnetic nanoporous carbon materials for selective enrichment of glycans for glycomics analysis. 25805188 2 7 theme surface 344:350 arg1 area 352:355 high surface area 339:355 high surface area 339:355 The obtained Co-ZIF-67 materials showed strong magnetic response, high surface area, a uniform size of mesopores and high carbon content. 25805188 3 8 theme glycomics 464:472 arg1 analysis 474:481 glycomics analysis 464:481 glycomics analysis 464:481 The Co-ZIF-67 materials were successfully applied to glycomics analysis by enriching N-linked glycans in bio-samples with high selectivity and efficiency. 25805188 0 9 theme glycomics 111:119 arg1 analysis 121:128 glycomics analysis 111:128 glycomics analysis 111:128 Designed synthesis of MOF-derived magnetic nanoporous carbon materials for selective enrichment of glycans for glycomics analysis. 25805188 3 10 with bio-samples 516:526 arg1 efficiency 554:563 efficiency 554:563 efficiency 554:563 The Co-ZIF-67 materials were successfully applied to glycomics analysis by enriching N-linked glycans in bio-samples with high selectivity and efficiency. 25805188 3 10 with bio-samples 516:526 arg1 selectivity 538:548 high selectivity 533:548 high selectivity 533:548 The Co-ZIF-67 materials were successfully applied to glycomics analysis by enriching N-linked glycans in bio-samples with high selectivity and efficiency. 25805188 2 11 theme uniform 360:366 arg1 size 368:371 a uniform size 358:371 a uniform size of mesopores 358:384 The obtained Co-ZIF-67 materials showed strong magnetic response, high surface area, a uniform size of mesopores and high carbon content. 25805188 1 12 theme carbon 255:260 arg1 precursor 262:270 a carbon precursor 253:270 a carbon precursor 253:270 In this work, magnetic nanoporous carbon (NPC) materials were synthesized by choosing a MOF as a sacrificial template and a carbon precursor. 25805188 1 12 theme carbon 255:260 arg1 MOF 219:221 a MOF 217:221 a MOF 217:221 In this work, magnetic nanoporous carbon (NPC) materials were synthesized by choosing a MOF as a sacrificial template and a carbon precursor. 25805188 0 13 theme MOF-derived 22:32 arg1 materials 61:69 MOF-derived magnetic nanoporous carbon materials 22:69 MOF-derived magnetic nanoporous carbon materials 22:69 Designed synthesis of MOF-derived magnetic nanoporous carbon materials for selective enrichment of glycans for glycomics analysis. 25805188 2 14 theme Co-ZIF-67 286:294 arg1 materials 296:304 The obtained Co-ZIF-67 materials 273:304 The obtained Co-ZIF-67 materials 273:304 The obtained Co-ZIF-67 materials showed strong magnetic response, high surface area, a uniform size of mesopores and high carbon content. 25805188 2 15 theme carbon 395:400 arg1 content 402:408 high carbon content 390:408 high carbon content 390:408 The obtained Co-ZIF-67 materials showed strong magnetic response, high surface area, a uniform size of mesopores and high carbon content. 25805188 3 16 link N-linked 496:503 arg1 glycans 505:511 N-linked glycans 496:511 N-linked glycans 496:511 The Co-ZIF-67 materials were successfully applied to glycomics analysis by enriching N-linked glycans in bio-samples with high selectivity and efficiency. 25805188 2 17 theme high 339:342 arg1 area 352:355 high surface area 339:355 high surface area 339:355 The obtained Co-ZIF-67 materials showed strong magnetic response, high surface area, a uniform size of mesopores and high carbon content. 25805188 2 18 theme high 390:393 arg1 content 402:408 high carbon content 390:408 high carbon content 390:408 The obtained Co-ZIF-67 materials showed strong magnetic response, high surface area, a uniform size of mesopores and high carbon content. 25805188 0 19 theme nanoporous 43:52 arg1 materials 61:69 MOF-derived magnetic nanoporous carbon materials 22:69 MOF-derived magnetic nanoporous carbon materials 22:69 Designed synthesis of MOF-derived magnetic nanoporous carbon materials for selective enrichment of glycans for glycomics analysis. 25805188 0 20 theme magnetic 34:41 arg1 materials 61:69 MOF-derived magnetic nanoporous carbon materials 22:69 MOF-derived magnetic nanoporous carbon materials 22:69 Designed synthesis of MOF-derived magnetic nanoporous carbon materials for selective enrichment of glycans for glycomics analysis. 25805188 2 21 theme mesopores 376:384 arg1 response 329:336 strong magnetic response 313:336 strong magnetic response 313:336 The obtained Co-ZIF-67 materials showed strong magnetic response, high surface area, a uniform size of mesopores and high carbon content. 25805188 2 21 theme mesopores 376:384 arg1 size 368:371 a uniform size 358:371 a uniform size of mesopores 358:384 The obtained Co-ZIF-67 materials showed strong magnetic response, high surface area, a uniform size of mesopores and high carbon content. 25805188 2 21 theme mesopores 376:384 arg1 content 402:408 high carbon content 390:408 high carbon content 390:408 The obtained Co-ZIF-67 materials showed strong magnetic response, high surface area, a uniform size of mesopores and high carbon content. 25805188 2 21 theme mesopores 376:384 arg1 area 352:355 high surface area 339:355 high surface area 339:355 The obtained Co-ZIF-67 materials showed strong magnetic response, high surface area, a uniform size of mesopores and high carbon content. 25805188 0 22 theme materials 61:69 arg1 synthesis 9:17 synthesis 9:17 synthesis of MOF-derived magnetic nanoporous carbon materials 9:69 Designed synthesis of MOF-derived magnetic nanoporous carbon materials for selective enrichment of glycans for glycomics analysis. 25805188 0 23 theme carbon 54:59 arg1 materials 61:69 MOF-derived magnetic nanoporous carbon materials 22:69 MOF-derived magnetic nanoporous carbon materials 22:69 Designed synthesis of MOF-derived magnetic nanoporous carbon materials for selective enrichment of glycans for glycomics analysis. 25805188 3 24 theme N-linked 496:503 arg1 glycans 505:511 N-linked glycans 496:511 N-linked glycans 496:511 The Co-ZIF-67 materials were successfully applied to glycomics analysis by enriching N-linked glycans in bio-samples with high selectivity and efficiency. 25805188 2 25 theme magnetic 320:327 arg1 response 329:336 strong magnetic response 313:336 strong magnetic response 313:336 The obtained Co-ZIF-67 materials showed strong magnetic response, high surface area, a uniform size of mesopores and high carbon content. 25805188 2 26 theme strong 313:318 arg1 response 329:336 strong magnetic response 313:336 strong magnetic response 313:336 The obtained Co-ZIF-67 materials showed strong magnetic response, high surface area, a uniform size of mesopores and high carbon content. 25805188 0 27 theme selective 75:83 arg1 enrichment 85:94 selective enrichment 75:94 selective enrichment of glycans for glycomics analysis 75:128 Designed synthesis of MOF-derived magnetic nanoporous carbon materials for selective enrichment of glycans for glycomics analysis. 25805188 1 28 theme magnetic 145:152 arg1 NPC 173:175 NPC 173:175 NPC 173:175 In this work, magnetic nanoporous carbon (NPC) materials were synthesized by choosing a MOF as a sacrificial template and a carbon precursor. 25805188 1 28 theme magnetic 145:152 arg1 carbon 165:170 magnetic nanoporous carbon 145:170 magnetic nanoporous carbon (NPC) materials 145:186 In this work, magnetic nanoporous carbon (NPC) materials were synthesized by choosing a MOF as a sacrificial template and a carbon precursor. 27613087 8 0 theme NLG 1451:1453 arg1 changes 1455:1461 the NA NLG changes 1444:1461 the NA NLG changes occurred by a removal of residue 66 and an addition at 266 1444:1520 However, when the NA NLG changes occurred by a removal of residue 66 and an addition at 266 were additionally accompanied, the HA-NA NLG mutant virus recovered the transmissibility of its parental virus. 27613087 6 1 theme addition 1284:1291 arg1 HA 1267:1268 the H7 HA 1260:1268 the H7 HA of double NLG addition and the N9 NA of various NLG patterns 1260:1329 Given the effects of HA-NA NLG changes with regard to viral transmission, we then generated the HA-NA NLG mutant viruses harboring the H7 HA of double NLG addition and the N9 NA of various NLG patterns. 27613087 1 2 theme virus-like 233:242 arg1 cases 260:264 seasonal virus-like human infection cases 224:264 seasonal virus-like human infection cases 224:264 Avian influenza H7N9 virus has posed a concern of potential human-to-human transmission by resulting in seasonal virus-like human infection cases. 27613087 3 3 theme mutant 617:622 arg1 viruses 624:630 NLG mutant viruses 613:630 NLG mutant viruses using either HA or NA gene of a H7N9 virus, A/Anhui/01/2013, 613:691 Based on the NLG signatures identified in the HA and NA genetic sequences of H7N9 viruses, we generated NLG mutant viruses using either HA or NA gene of a H7N9 virus, A/Anhui/01/2013, by reverse genetics on the 2009 pandemic H1N1 virus backbone. 27613087 8 4 theme NLG 1563:1565 arg1 virus 1574:1578 the HA-NA NLG mutant virus 1553:1578 the HA-NA NLG mutant virus 1553:1578 However, when the NA NLG changes occurred by a removal of residue 66 and an addition at 266 were additionally accompanied, the HA-NA NLG mutant virus recovered the transmissibility of its parental virus. 27613087 6 5 theme double 1273:1278 arg1 addition 1284:1291 double NLG addition 1273:1291 double NLG addition 1273:1291 Given the effects of HA-NA NLG changes with regard to viral transmission, we then generated the HA-NA NLG mutant viruses harboring the H7 HA of double NLG addition and the N9 NA of various NLG patterns. 27613087 1 6 theme H7N9 136:139 arg1 virus 141:145 Avian influenza H7N9 virus 120:145 Avian influenza H7N9 virus 120:145 Avian influenza H7N9 virus has posed a concern of potential human-to-human transmission by resulting in seasonal virus-like human infection cases. 27613087 8 7 theme parental 1618:1625 arg1 virus 1627:1631 its parental virus 1614:1631 its parental virus 1614:1631 However, when the NA NLG changes occurred by a removal of residue 66 and an addition at 266 were additionally accompanied, the HA-NA NLG mutant virus recovered the transmissibility of its parental virus. 27613087 3 8 theme NA 651:652 arg1 gene 654:657 NA gene 651:657 NA gene of a H7N9 virus, A/Anhui/01/2013, 651:691 Based on the NLG signatures identified in the HA and NA genetic sequences of H7N9 viruses, we generated NLG mutant viruses using either HA or NA gene of a H7N9 virus, A/Anhui/01/2013, by reverse genetics on the 2009 pandemic H1N1 virus backbone. 27613087 0 9 theme H7N9 92:95 arg1 virus 98:102 avian influenza A(H7N9) virus 74:102 avian influenza A(H7N9) virus 74:102 Effects of HA and NA glycosylation pattern changes on the transmission of avian influenza A(H7N9) virus in guinea pigs. 27613087 5 10 theme NA 916:917 arg1 protein 919:925 the N9 NA protein 909:925 the N9 NA protein 909:925 Intriguingly, however, the NLG changes in the N9 NA protein, such as a removal from residue 42 or 66 or an addition at residue 266, increased transmissibility of the mutant viruses by more than 33%, 50%, and 16%, respectively, compared with a parental N9 virus. 27613087 5 10 theme NA 916:917 arg1 such 928:931 such 928:931 such 928:931 Intriguingly, however, the NLG changes in the N9 NA protein, such as a removal from residue 42 or 66 or an addition at residue 266, increased transmissibility of the mutant viruses by more than 33%, 50%, and 16%, respectively, compared with a parental N9 virus. 27613087 8 11 theme NA 1448:1449 arg1 changes 1455:1461 the NA NLG changes 1444:1461 the NA NLG changes occurred by a removal of residue 66 and an addition at 266 1444:1520 However, when the NA NLG changes occurred by a removal of residue 66 and an addition at 266 were additionally accompanied, the HA-NA NLG mutant virus recovered the transmissibility of its parental virus. 27613087 7 12 theme HA 1347:1348 arg1 mutants 1354:1360 the HA NLG mutants 1343:1360 the HA NLG mutants 1343:1360 As seen in the HA NLG mutants above, the double NLG-added H7 HA decreased viral transmissibility. 27613087 4 13 theme pattern 793:799 arg1 changes 801:807 NLG pattern changes 789:807 NLG pattern changes 789:807 For the H7 HA NLG mutant viruses, NLG pattern changes appeared to reduce viral transmissibility in guinea pigs. 27613087 0 14 from transmission 58:69 arg1 pigs 114:117 guinea pigs 107:117 guinea pigs 107:117 Effects of HA and NA glycosylation pattern changes on the transmission of avian influenza A(H7N9) virus in guinea pigs. 27613087 3 15 theme H7N9 664:667 arg1 A/Anhui/01/2013 676:690 A/Anhui/01/2013 676:690 A/Anhui/01/2013 676:690 Based on the NLG signatures identified in the HA and NA genetic sequences of H7N9 viruses, we generated NLG mutant viruses using either HA or NA gene of a H7N9 virus, A/Anhui/01/2013, by reverse genetics on the 2009 pandemic H1N1 virus backbone. 27613087 3 15 theme H7N9 664:667 arg1 virus 669:673 a H7N9 virus 662:673 a H7N9 virus 662:673 Based on the NLG signatures identified in the HA and NA genetic sequences of H7N9 viruses, we generated NLG mutant viruses using either HA or NA gene of a H7N9 virus, A/Anhui/01/2013, by reverse genetics on the 2009 pandemic H1N1 virus backbone. 27613087 0 16 theme virus 98:102 arg1 transmission 58:69 the transmission 54:69 the transmission of avian influenza A(H7N9) virus in guinea pigs 54:117 Effects of HA and NA glycosylation pattern changes on the transmission of avian influenza A(H7N9) virus in guinea pigs. 27613087 3 17 theme NLG 522:524 arg1 signatures 526:535 the NLG signatures 518:535 the NLG signatures identified in the HA and NA genetic sequences of H7N9 viruses 518:597 Based on the NLG signatures identified in the HA and NA genetic sequences of H7N9 viruses, we generated NLG mutant viruses using either HA or NA gene of a H7N9 virus, A/Anhui/01/2013, by reverse genetics on the 2009 pandemic H1N1 virus backbone. 27613087 6 18 theme patterns 1322:1329 arg1 NA 1304:1305 the N9 NA 1297:1305 the N9 NA 1297:1305 Given the effects of HA-NA NLG changes with regard to viral transmission, we then generated the HA-NA NLG mutant viruses harboring the H7 HA of double NLG addition and the N9 NA of various NLG patterns. 27613087 6 18 theme patterns 1322:1329 arg1 addition 1284:1291 double NLG addition 1273:1291 double NLG addition 1273:1291 Given the effects of HA-NA NLG changes with regard to viral transmission, we then generated the HA-NA NLG mutant viruses harboring the H7 HA of double NLG addition and the N9 NA of various NLG patterns. 27613087 4 19 theme HA 766:767 arg1 NLG 769:771 the H7 HA NLG 759:771 the H7 HA NLG mutant viruses 759:786 For the H7 HA NLG mutant viruses, NLG pattern changes appeared to reduce viral transmissibility in guinea pigs. 27613087 2 20 link N-linked 416:423 arg1 patterns 445:452 N-linked glycosylation (NLG) patterns 416:452 N-linked glycosylation (NLG) patterns 416:452 To address the issue of sustained human infection with the H7N9 virus, here we investigated the effects of hemagglutinin (HA) and neuraminidase (NA) N-linked glycosylation (NLG) patterns on influenza virus transmission in a guinea pig model. 27613087 0 21 theme guinea 107:112 arg1 pigs 114:117 guinea pigs 107:117 guinea pigs 107:117 Effects of HA and NA glycosylation pattern changes on the transmission of avian influenza A(H7N9) virus in guinea pigs. 27613087 6 22 theme various 1310:1316 arg1 patterns 1322:1329 various NLG patterns 1310:1329 various NLG patterns 1310:1329 Given the effects of HA-NA NLG changes with regard to viral transmission, we then generated the HA-NA NLG mutant viruses harboring the H7 HA of double NLG addition and the N9 NA of various NLG patterns. 27613087 3 23 theme H1N1 734:737 arg1 backbone 745:752 the 2009 pandemic H1N1 virus backbone 716:752 the 2009 pandemic H1N1 virus backbone 716:752 Based on the NLG signatures identified in the HA and NA genetic sequences of H7N9 viruses, we generated NLG mutant viruses using either HA or NA gene of a H7N9 virus, A/Anhui/01/2013, by reverse genetics on the 2009 pandemic H1N1 virus backbone. 27613087 4 24 theme mutant 773:778 arg1 viruses 780:786 the H7 HA NLG mutant viruses 759:786 the H7 HA NLG mutant viruses 759:786 For the H7 HA NLG mutant viruses, NLG pattern changes appeared to reduce viral transmissibility in guinea pigs. 27613087 6 25 theme NA 1304:1305 arg1 HA 1267:1268 the H7 HA 1260:1268 the H7 HA of double NLG addition and the N9 NA of various NLG patterns 1260:1329 Given the effects of HA-NA NLG changes with regard to viral transmission, we then generated the HA-NA NLG mutant viruses harboring the H7 HA of double NLG addition and the N9 NA of various NLG patterns. 27613087 2 26 theme NLG 440:442 arg1 patterns 445:452 N-linked glycosylation (NLG) patterns 416:452 N-linked glycosylation (NLG) patterns 416:452 To address the issue of sustained human infection with the H7N9 virus, here we investigated the effects of hemagglutinin (HA) and neuraminidase (NA) N-linked glycosylation (NLG) patterns on influenza virus transmission in a guinea pig model. 27613087 9 27 theme HA-NA 1676:1680 arg1 changes 1686:1692 specific HA-NA NLG changes 1667:1692 specific HA-NA NLG changes 1667:1692 These demonstrate the effects of specific HA-NA NLG changes on the H7N9 virus transmission by highlighting the importance of a HA-NA functional balance. 27613087 8 28 theme residue 1488:1494 arg1 removal 1477:1483 a removal 1475:1483 a removal of residue 66 1475:1497 However, when the NA NLG changes occurred by a removal of residue 66 and an addition at 266 were additionally accompanied, the HA-NA NLG mutant virus recovered the transmissibility of its parental virus. 27613087 8 28 theme residue 1488:1494 arg1 addition 1506:1513 an addition 1503:1513 an addition at 266 1503:1520 However, when the NA NLG changes occurred by a removal of residue 66 and an addition at 266 were additionally accompanied, the HA-NA NLG mutant virus recovered the transmissibility of its parental virus. 27613087 2 29 theme glycosylation 425:437 arg1 patterns 445:452 N-linked glycosylation (NLG) patterns 416:452 N-linked glycosylation (NLG) patterns 416:452 To address the issue of sustained human infection with the H7N9 virus, here we investigated the effects of hemagglutinin (HA) and neuraminidase (NA) N-linked glycosylation (NLG) patterns on influenza virus transmission in a guinea pig model. 27613087 2 30 theme guinea 491:496 arg1 pig 498:500 a guinea pig 489:500 a guinea pig model 489:506 To address the issue of sustained human infection with the H7N9 virus, here we investigated the effects of hemagglutinin (HA) and neuraminidase (NA) N-linked glycosylation (NLG) patterns on influenza virus transmission in a guinea pig model. 27613087 8 31 from 266 1518:1520 arg1 removal 1477:1483 a removal 1475:1483 a removal of residue 66 1475:1497 However, when the NA NLG changes occurred by a removal of residue 66 and an addition at 266 were additionally accompanied, the HA-NA NLG mutant virus recovered the transmissibility of its parental virus. 27613087 8 31 from 266 1518:1520 arg1 addition 1506:1513 an addition 1503:1513 an addition at 266 1503:1520 However, when the NA NLG changes occurred by a removal of residue 66 and an addition at 266 were additionally accompanied, the HA-NA NLG mutant virus recovered the transmissibility of its parental virus. 27613087 1 32 theme Avian 120:124 arg1 virus 141:145 Avian influenza H7N9 virus 120:145 Avian influenza H7N9 virus 120:145 Avian influenza H7N9 virus has posed a concern of potential human-to-human transmission by resulting in seasonal virus-like human infection cases. 27613087 7 33 theme viral 1406:1410 arg1 transmissibility 1412:1427 viral transmissibility 1406:1427 viral transmissibility 1406:1427 As seen in the HA NLG mutants above, the double NLG-added H7 HA decreased viral transmissibility. 27613087 2 34 theme influenza 457:465 arg1 transmission 473:484 influenza virus transmission 457:484 influenza virus transmission 457:484 To address the issue of sustained human infection with the H7N9 virus, here we investigated the effects of hemagglutinin (HA) and neuraminidase (NA) N-linked glycosylation (NLG) patterns on influenza virus transmission in a guinea pig model. 27613087 0 35 from Effects 0:6 arg1 transmission 58:69 the transmission 54:69 the transmission of avian influenza A(H7N9) virus in guinea pigs 54:117 Effects of HA and NA glycosylation pattern changes on the transmission of avian influenza A(H7N9) virus in guinea pigs. 27613087 3 36 theme reverse 696:702 arg1 genetics 704:711 reverse genetics 696:711 reverse genetics 696:711 Based on the NLG signatures identified in the HA and NA genetic sequences of H7N9 viruses, we generated NLG mutant viruses using either HA or NA gene of a H7N9 virus, A/Anhui/01/2013, by reverse genetics on the 2009 pandemic H1N1 virus backbone. 27613087 0 37 theme avian 74:78 arg1 virus 98:102 avian influenza A(H7N9) virus 74:102 avian influenza A(H7N9) virus 74:102 Effects of HA and NA glycosylation pattern changes on the transmission of avian influenza A(H7N9) virus in guinea pigs. 27613087 9 38 theme virus 1706:1710 arg1 transmission 1712:1723 the H7N9 virus transmission 1697:1723 the H7N9 virus transmission 1697:1723 These demonstrate the effects of specific HA-NA NLG changes on the H7N9 virus transmission by highlighting the importance of a HA-NA functional balance. 27613087 2 39 theme pig 498:500 arg1 model 502:506 a guinea pig model 489:506 a guinea pig model 489:506 To address the issue of sustained human infection with the H7N9 virus, here we investigated the effects of hemagglutinin (HA) and neuraminidase (NA) N-linked glycosylation (NLG) patterns on influenza virus transmission in a guinea pig model. 27613087 5 40 theme mutant 1033:1038 arg1 viruses 1040:1046 the mutant viruses 1029:1046 the mutant viruses 1029:1046 Intriguingly, however, the NLG changes in the N9 NA protein, such as a removal from residue 42 or 66 or an addition at residue 266, increased transmissibility of the mutant viruses by more than 33%, 50%, and 16%, respectively, compared with a parental N9 virus. 27613087 7 41 theme NLG-added 1380:1388 arg1 H7 1390:1391 the double NLG-added H7 1369:1391 the double NLG-added H7 1369:1391 As seen in the HA NLG mutants above, the double NLG-added H7 HA decreased viral transmissibility. 27613087 5 42 theme parental 1110:1117 arg1 virus 1122:1126 a parental N9 virus 1108:1126 a parental N9 virus 1108:1126 Intriguingly, however, the NLG changes in the N9 NA protein, such as a removal from residue 42 or 66 or an addition at residue 266, increased transmissibility of the mutant viruses by more than 33%, 50%, and 16%, respectively, compared with a parental N9 virus. 27613087 1 43 theme human 244:248 arg1 cases 260:264 seasonal virus-like human infection cases 224:264 seasonal virus-like human infection cases 224:264 Avian influenza H7N9 virus has posed a concern of potential human-to-human transmission by resulting in seasonal virus-like human infection cases. 27613087 2 44 theme hemagglutinin 374:386 arg1 effects 363:369 the effects 359:369 the effects of hemagglutinin (HA) and neuraminidase (NA) N-linked glycosylation (NLG) patterns on influenza virus transmission 359:484 To address the issue of sustained human infection with the H7N9 virus, here we investigated the effects of hemagglutinin (HA) and neuraminidase (NA) N-linked glycosylation (NLG) patterns on influenza virus transmission in a guinea pig model. 27613087 0 45 theme HA 11:12 arg1 Effects 0:6 Effects 0:6 Effects of HA and NA glycosylation pattern changes on the transmission of avian influenza A(H7N9) virus in guinea pigs 0:117 Effects of HA and NA glycosylation pattern changes on the transmission of avian influenza A(H7N9) virus in guinea pigs. 27613087 3 46 theme genetic 565:571 arg1 sequences 573:581 the HA and NA genetic sequences 551:581 the HA and NA genetic sequences of H7N9 viruses 551:597 Based on the NLG signatures identified in the HA and NA genetic sequences of H7N9 viruses, we generated NLG mutant viruses using either HA or NA gene of a H7N9 virus, A/Anhui/01/2013, by reverse genetics on the 2009 pandemic H1N1 virus backbone. 27613087 5 47 from 66 965:966 arg1 removal 938:944 a removal 936:944 a removal from residue 42 or 66 936:966 Intriguingly, however, the NLG changes in the N9 NA protein, such as a removal from residue 42 or 66 or an addition at residue 266, increased transmissibility of the mutant viruses by more than 33%, 50%, and 16%, respectively, compared with a parental N9 virus. 27613087 5 47 from 66 965:966 arg1 addition 974:981 an addition 971:981 an addition at residue 266 971:996 Intriguingly, however, the NLG changes in the N9 NA protein, such as a removal from residue 42 or 66 or an addition at residue 266, increased transmissibility of the mutant viruses by more than 33%, 50%, and 16%, respectively, compared with a parental N9 virus. 27613087 0 48 theme NA 18:19 arg1 Effects 0:6 Effects 0:6 Effects of HA and NA glycosylation pattern changes on the transmission of avian influenza A(H7N9) virus in guinea pigs 0:117 Effects of HA and NA glycosylation pattern changes on the transmission of avian influenza A(H7N9) virus in guinea pigs. 27613087 2 49 with infection 307:315 arg1 virus 331:335 the H7N9 virus 322:335 the H7N9 virus 322:335 To address the issue of sustained human infection with the H7N9 virus, here we investigated the effects of hemagglutinin (HA) and neuraminidase (NA) N-linked glycosylation (NLG) patterns on influenza virus transmission in a guinea pig model. 27613087 8 50 attach removal 1477:1483 arg2 residue 1488:1494 residue 66 1488:1497 residue 66 1488:1497 However, when the NA NLG changes occurred by a removal of residue 66 and an addition at 266 were additionally accompanied, the HA-NA NLG mutant virus recovered the transmissibility of its parental virus. 27613087 8 50 attach removal 1477:1483 arg3 266 1518:1520 266 1518:1520 266 1518:1520 However, when the NA NLG changes occurred by a removal of residue 66 and an addition at 266 were additionally accompanied, the HA-NA NLG mutant virus recovered the transmissibility of its parental virus. 27613087 9 51 theme HA-NA 1761:1765 arg1 balance 1778:1784 a HA-NA functional balance 1759:1784 a HA-NA functional balance 1759:1784 These demonstrate the effects of specific HA-NA NLG changes on the H7N9 virus transmission by highlighting the importance of a HA-NA functional balance. 27613087 2 52 dep hemagglutinin 374:386 arg1 patterns 445:452 N-linked glycosylation (NLG) patterns 416:452 N-linked glycosylation (NLG) patterns 416:452 To address the issue of sustained human infection with the H7N9 virus, here we investigated the effects of hemagglutinin (HA) and neuraminidase (NA) N-linked glycosylation (NLG) patterns on influenza virus transmission in a guinea pig model. 27613087 2 53 theme infection 307:315 arg1 issue 282:286 the issue 278:286 the issue of sustained human infection with the H7N9 virus 278:335 To address the issue of sustained human infection with the H7N9 virus, here we investigated the effects of hemagglutinin (HA) and neuraminidase (NA) N-linked glycosylation (NLG) patterns on influenza virus transmission in a guinea pig model. 27613087 0 54 theme pattern 35:41 arg1 changes 43:49 glycosylation pattern changes 21:49 glycosylation pattern changes 21:49 Effects of HA and NA glycosylation pattern changes on the transmission of avian influenza A(H7N9) virus in guinea pigs. 27613087 5 55 theme NLG 894:896 arg1 changes 898:904 the NLG changes 890:904 the NLG changes in the N9 NA protein, such as a removal from residue 42 or 66 or an addition at residue 266, 890:997 Intriguingly, however, the NLG changes in the N9 NA protein, such as a removal from residue 42 or 66 or an addition at residue 266, increased transmissibility of the mutant viruses by more than 33%, 50%, and 16%, respectively, compared with a parental N9 virus. 27613087 3 56 theme viruses 591:597 arg1 sequences 573:581 the HA and NA genetic sequences 551:581 the HA and NA genetic sequences of H7N9 viruses 551:597 Based on the NLG signatures identified in the HA and NA genetic sequences of H7N9 viruses, we generated NLG mutant viruses using either HA or NA gene of a H7N9 virus, A/Anhui/01/2013, by reverse genetics on the 2009 pandemic H1N1 virus backbone. 27613087 2 57 theme sustained 291:299 arg1 infection 307:315 sustained human infection 291:315 sustained human infection with the H7N9 virus 291:335 To address the issue of sustained human infection with the H7N9 virus, here we investigated the effects of hemagglutinin (HA) and neuraminidase (NA) N-linked glycosylation (NLG) patterns on influenza virus transmission in a guinea pig model. 27613087 6 58 theme mutant 1235:1240 arg1 viruses 1242:1248 the HA-NA NLG mutant viruses 1221:1248 the HA-NA NLG mutant viruses harboring the H7 HA of double NLG addition and the N9 NA of various NLG patterns 1221:1329 Given the effects of HA-NA NLG changes with regard to viral transmission, we then generated the HA-NA NLG mutant viruses harboring the H7 HA of double NLG addition and the N9 NA of various NLG patterns. 27613087 5 59 theme viruses 1040:1046 arg1 transmissibility 1009:1024 transmissibility 1009:1024 transmissibility of the mutant viruses 1009:1046 Intriguingly, however, the NLG changes in the N9 NA protein, such as a removal from residue 42 or 66 or an addition at residue 266, increased transmissibility of the mutant viruses by more than 33%, 50%, and 16%, respectively, compared with a parental N9 virus. 27613087 0 60 dep HA 11:12 arg1 changes 43:49 glycosylation pattern changes 21:49 glycosylation pattern changes 21:49 Effects of HA and NA glycosylation pattern changes on the transmission of avian influenza A(H7N9) virus in guinea pigs. 27613087 2 61 from effects 363:369 arg1 transmission 473:484 influenza virus transmission 457:484 influenza virus transmission 457:484 To address the issue of sustained human infection with the H7N9 virus, here we investigated the effects of hemagglutinin (HA) and neuraminidase (NA) N-linked glycosylation (NLG) patterns on influenza virus transmission in a guinea pig model. 27613087 6 62 theme HA-NA 1225:1229 arg1 viruses 1242:1248 the HA-NA NLG mutant viruses 1221:1248 the HA-NA NLG mutant viruses harboring the H7 HA of double NLG addition and the N9 NA of various NLG patterns 1221:1329 Given the effects of HA-NA NLG changes with regard to viral transmission, we then generated the HA-NA NLG mutant viruses harboring the H7 HA of double NLG addition and the N9 NA of various NLG patterns. 27613087 4 63 from transmissibility 834:849 arg1 pigs 861:864 guinea pigs 854:864 guinea pigs 854:864 For the H7 HA NLG mutant viruses, NLG pattern changes appeared to reduce viral transmissibility in guinea pigs. 27613087 6 64 theme changes 1160:1166 arg1 effects 1139:1145 the effects 1135:1145 the effects of HA-NA NLG changes with regard to viral transmission 1135:1200 Given the effects of HA-NA NLG changes with regard to viral transmission, we then generated the HA-NA NLG mutant viruses harboring the H7 HA of double NLG addition and the N9 NA of various NLG patterns. 27613087 4 65 theme guinea 854:859 arg1 pigs 861:864 guinea pigs 854:864 guinea pigs 854:864 For the H7 HA NLG mutant viruses, NLG pattern changes appeared to reduce viral transmissibility in guinea pigs. 27613087 8 66 theme HA-NA 1557:1561 arg1 virus 1574:1578 the HA-NA NLG mutant virus 1553:1578 the HA-NA NLG mutant virus 1553:1578 However, when the NA NLG changes occurred by a removal of residue 66 and an addition at 266 were additionally accompanied, the HA-NA NLG mutant virus recovered the transmissibility of its parental virus. 27613087 9 67 theme changes 1686:1692 arg1 effects 1656:1662 the effects 1652:1662 the effects of specific HA-NA NLG changes on the H7N9 virus transmission 1652:1723 These demonstrate the effects of specific HA-NA NLG changes on the H7N9 virus transmission by highlighting the importance of a HA-NA functional balance. 27613087 1 68 theme seasonal 224:231 arg1 cases 260:264 seasonal virus-like human infection cases 224:264 seasonal virus-like human infection cases 224:264 Avian influenza H7N9 virus has posed a concern of potential human-to-human transmission by resulting in seasonal virus-like human infection cases. 27613087 8 69 theme mutant 1567:1572 arg1 virus 1574:1578 the HA-NA NLG mutant virus 1553:1578 the HA-NA NLG mutant virus 1553:1578 However, when the NA NLG changes occurred by a removal of residue 66 and an addition at 266 were additionally accompanied, the HA-NA NLG mutant virus recovered the transmissibility of its parental virus. 27613087 6 70 theme NLG 1280:1282 arg1 addition 1284:1291 double NLG addition 1273:1291 double NLG addition 1273:1291 Given the effects of HA-NA NLG changes with regard to viral transmission, we then generated the HA-NA NLG mutant viruses harboring the H7 HA of double NLG addition and the N9 NA of various NLG patterns. 27613087 1 71 theme influenza 126:134 arg1 virus 141:145 Avian influenza H7N9 virus 120:145 Avian influenza H7N9 virus 120:145 Avian influenza H7N9 virus has posed a concern of potential human-to-human transmission by resulting in seasonal virus-like human infection cases. 27613087 2 72 theme neuraminidase 397:409 arg1 effects 363:369 the effects 359:369 the effects of hemagglutinin (HA) and neuraminidase (NA) N-linked glycosylation (NLG) patterns on influenza virus transmission 359:484 To address the issue of sustained human infection with the H7N9 virus, here we investigated the effects of hemagglutinin (HA) and neuraminidase (NA) N-linked glycosylation (NLG) patterns on influenza virus transmission in a guinea pig model. 27613087 5 73 from residue 986:992 arg1 removal 938:944 a removal 936:944 a removal from residue 42 or 66 936:966 Intriguingly, however, the NLG changes in the N9 NA protein, such as a removal from residue 42 or 66 or an addition at residue 266, increased transmissibility of the mutant viruses by more than 33%, 50%, and 16%, respectively, compared with a parental N9 virus. 27613087 5 73 from residue 986:992 arg1 addition 974:981 an addition 971:981 an addition at residue 266 971:996 Intriguingly, however, the NLG changes in the N9 NA protein, such as a removal from residue 42 or 66 or an addition at residue 266, increased transmissibility of the mutant viruses by more than 33%, 50%, and 16%, respectively, compared with a parental N9 virus. 27613087 7 74 theme NLG 1350:1352 arg1 mutants 1354:1360 the HA NLG mutants 1343:1360 the HA NLG mutants 1343:1360 As seen in the HA NLG mutants above, the double NLG-added H7 HA decreased viral transmissibility. 27613087 9 75 theme functional 1767:1776 arg1 balance 1778:1784 a HA-NA functional balance 1759:1784 a HA-NA functional balance 1759:1784 These demonstrate the effects of specific HA-NA NLG changes on the H7N9 virus transmission by highlighting the importance of a HA-NA functional balance. 27613087 6 76 theme H7 1264:1265 arg1 HA 1267:1268 the H7 HA 1260:1268 the H7 HA of double NLG addition and the N9 NA of various NLG patterns 1260:1329 Given the effects of HA-NA NLG changes with regard to viral transmission, we then generated the HA-NA NLG mutant viruses harboring the H7 HA of double NLG addition and the N9 NA of various NLG patterns. 27613087 4 77 theme NLG 789:791 arg1 changes 801:807 NLG pattern changes 789:807 NLG pattern changes 789:807 For the H7 HA NLG mutant viruses, NLG pattern changes appeared to reduce viral transmissibility in guinea pigs. 27613087 3 78 theme virus 669:673 arg1 HA 645:646 HA 645:646 HA 645:646 Based on the NLG signatures identified in the HA and NA genetic sequences of H7N9 viruses, we generated NLG mutant viruses using either HA or NA gene of a H7N9 virus, A/Anhui/01/2013, by reverse genetics on the 2009 pandemic H1N1 virus backbone. 27613087 3 78 theme virus 669:673 arg1 gene 654:657 NA gene 651:657 NA gene of a H7N9 virus, A/Anhui/01/2013, 651:691 Based on the NLG signatures identified in the HA and NA genetic sequences of H7N9 viruses, we generated NLG mutant viruses using either HA or NA gene of a H7N9 virus, A/Anhui/01/2013, by reverse genetics on the 2009 pandemic H1N1 virus backbone. 27613087 8 79 theme virus 1627:1631 arg1 transmissibility 1594:1609 the transmissibility 1590:1609 the transmissibility of its parental virus 1590:1631 However, when the NA NLG changes occurred by a removal of residue 66 and an addition at 266 were additionally accompanied, the HA-NA NLG mutant virus recovered the transmissibility of its parental virus. 27613087 6 80 theme NLG 1318:1320 arg1 patterns 1322:1329 various NLG patterns 1310:1329 various NLG patterns 1310:1329 Given the effects of HA-NA NLG changes with regard to viral transmission, we then generated the HA-NA NLG mutant viruses harboring the H7 HA of double NLG addition and the N9 NA of various NLG patterns. 27613087 4 81 theme H7 763:764 arg1 NLG 769:771 the H7 HA NLG 759:771 the H7 HA NLG mutant viruses 759:786 For the H7 HA NLG mutant viruses, NLG pattern changes appeared to reduce viral transmissibility in guinea pigs. 27613087 9 82 theme balance 1778:1784 arg1 importance 1745:1754 the importance 1741:1754 the importance of a HA-NA functional balance 1741:1784 These demonstrate the effects of specific HA-NA NLG changes on the H7N9 virus transmission by highlighting the importance of a HA-NA functional balance. 27613087 3 83 theme virus 739:743 arg1 backbone 745:752 the 2009 pandemic H1N1 virus backbone 716:752 the 2009 pandemic H1N1 virus backbone 716:752 Based on the NLG signatures identified in the HA and NA genetic sequences of H7N9 viruses, we generated NLG mutant viruses using either HA or NA gene of a H7N9 virus, A/Anhui/01/2013, by reverse genetics on the 2009 pandemic H1N1 virus backbone. 27613087 4 84 theme NLG 769:771 arg1 viruses 780:786 the H7 HA NLG mutant viruses 759:786 the H7 HA NLG mutant viruses 759:786 For the H7 HA NLG mutant viruses, NLG pattern changes appeared to reduce viral transmissibility in guinea pigs. 27613087 9 85 theme specific 1667:1674 arg1 changes 1686:1692 specific HA-NA NLG changes 1667:1692 specific HA-NA NLG changes 1667:1692 These demonstrate the effects of specific HA-NA NLG changes on the H7N9 virus transmission by highlighting the importance of a HA-NA functional balance. 27613087 6 86 theme HA-NA 1150:1154 arg1 changes 1160:1166 HA-NA NLG changes 1150:1166 HA-NA NLG changes with regard to viral transmission 1150:1200 Given the effects of HA-NA NLG changes with regard to viral transmission, we then generated the HA-NA NLG mutant viruses harboring the H7 HA of double NLG addition and the N9 NA of various NLG patterns. 27613087 5 87 theme N9 913:914 arg1 protein 919:925 the N9 NA protein 909:925 the N9 NA protein 909:925 Intriguingly, however, the NLG changes in the N9 NA protein, such as a removal from residue 42 or 66 or an addition at residue 266, increased transmissibility of the mutant viruses by more than 33%, 50%, and 16%, respectively, compared with a parental N9 virus. 27613087 5 87 theme N9 913:914 arg1 such 928:931 such 928:931 such 928:931 Intriguingly, however, the NLG changes in the N9 NA protein, such as a removal from residue 42 or 66 or an addition at residue 266, increased transmissibility of the mutant viruses by more than 33%, 50%, and 16%, respectively, compared with a parental N9 virus. 27613087 6 88 theme N9 1301:1302 arg1 NA 1304:1305 the N9 NA 1297:1305 the N9 NA 1297:1305 Given the effects of HA-NA NLG changes with regard to viral transmission, we then generated the HA-NA NLG mutant viruses harboring the H7 HA of double NLG addition and the N9 NA of various NLG patterns. 27613087 3 89 theme pandemic 725:732 arg1 backbone 745:752 the 2009 pandemic H1N1 virus backbone 716:752 the 2009 pandemic H1N1 virus backbone 716:752 Based on the NLG signatures identified in the HA and NA genetic sequences of H7N9 viruses, we generated NLG mutant viruses using either HA or NA gene of a H7N9 virus, A/Anhui/01/2013, by reverse genetics on the 2009 pandemic H1N1 virus backbone. 27613087 4 90 theme viral 828:832 arg1 transmissibility 834:849 viral transmissibility 828:849 viral transmissibility in guinea pigs 828:864 For the H7 HA NLG mutant viruses, NLG pattern changes appeared to reduce viral transmissibility in guinea pigs. 27613087 9 91 theme NLG 1682:1684 arg1 changes 1686:1692 specific HA-NA NLG changes 1667:1692 specific HA-NA NLG changes 1667:1692 These demonstrate the effects of specific HA-NA NLG changes on the H7N9 virus transmission by highlighting the importance of a HA-NA functional balance. 27613087 1 92 theme potential 170:178 arg1 transmission 195:206 potential human-to-human transmission 170:206 potential human-to-human transmission 170:206 Avian influenza H7N9 virus has posed a concern of potential human-to-human transmission by resulting in seasonal virus-like human infection cases. 27613087 5 93 from changes 898:904 arg1 protein 919:925 the N9 NA protein 909:925 the N9 NA protein 909:925 Intriguingly, however, the NLG changes in the N9 NA protein, such as a removal from residue 42 or 66 or an addition at residue 266, increased transmissibility of the mutant viruses by more than 33%, 50%, and 16%, respectively, compared with a parental N9 virus. 27613087 5 93 from changes 898:904 arg1 such 928:931 such 928:931 such 928:931 Intriguingly, however, the NLG changes in the N9 NA protein, such as a removal from residue 42 or 66 or an addition at residue 266, increased transmissibility of the mutant viruses by more than 33%, 50%, and 16%, respectively, compared with a parental N9 virus. 27613087 2 94 theme N-linked 416:423 arg1 patterns 445:452 N-linked glycosylation (NLG) patterns 416:452 N-linked glycosylation (NLG) patterns 416:452 To address the issue of sustained human infection with the H7N9 virus, here we investigated the effects of hemagglutinin (HA) and neuraminidase (NA) N-linked glycosylation (NLG) patterns on influenza virus transmission in a guinea pig model. 27613087 0 95 theme influenza 80:88 arg1 virus 98:102 avian influenza A(H7N9) virus 74:102 avian influenza A(H7N9) virus 74:102 Effects of HA and NA glycosylation pattern changes on the transmission of avian influenza A(H7N9) virus in guinea pigs. 27613087 9 96 theme H7N9 1701:1704 arg1 transmission 1712:1723 the H7N9 virus transmission 1697:1723 the H7N9 virus transmission 1697:1723 These demonstrate the effects of specific HA-NA NLG changes on the H7N9 virus transmission by highlighting the importance of a HA-NA functional balance. 27613087 6 97 theme viral 1183:1187 arg1 transmission 1189:1200 viral transmission 1183:1200 viral transmission 1183:1200 Given the effects of HA-NA NLG changes with regard to viral transmission, we then generated the HA-NA NLG mutant viruses harboring the H7 HA of double NLG addition and the N9 NA of various NLG patterns. 27613087 1 98 theme infection 250:258 arg1 cases 260:264 seasonal virus-like human infection cases 224:264 seasonal virus-like human infection cases 224:264 Avian influenza H7N9 virus has posed a concern of potential human-to-human transmission by resulting in seasonal virus-like human infection cases. 27613087 7 99 theme double 1373:1378 arg1 H7 1390:1391 the double NLG-added H7 1369:1391 the double NLG-added H7 1369:1391 As seen in the HA NLG mutants above, the double NLG-added H7 HA decreased viral transmissibility. 27613087 9 100 from effects 1656:1662 arg1 transmission 1712:1723 the H7N9 virus transmission 1697:1723 the H7N9 virus transmission 1697:1723 These demonstrate the effects of specific HA-NA NLG changes on the H7N9 virus transmission by highlighting the importance of a HA-NA functional balance. 27613087 3 101 theme NA 562:563 arg1 sequences 573:581 the HA and NA genetic sequences 551:581 the HA and NA genetic sequences of H7N9 viruses 551:597 Based on the NLG signatures identified in the HA and NA genetic sequences of H7N9 viruses, we generated NLG mutant viruses using either HA or NA gene of a H7N9 virus, A/Anhui/01/2013, by reverse genetics on the 2009 pandemic H1N1 virus backbone. 27613087 0 102 theme glycosylation 21:33 arg1 changes 43:49 glycosylation pattern changes 21:49 glycosylation pattern changes 21:49 Effects of HA and NA glycosylation pattern changes on the transmission of avian influenza A(H7N9) virus in guinea pigs. 27613087 3 103 theme HA 555:556 arg1 sequences 573:581 the HA and NA genetic sequences 551:581 the HA and NA genetic sequences of H7N9 viruses 551:597 Based on the NLG signatures identified in the HA and NA genetic sequences of H7N9 viruses, we generated NLG mutant viruses using either HA or NA gene of a H7N9 virus, A/Anhui/01/2013, by reverse genetics on the 2009 pandemic H1N1 virus backbone. 27613087 1 104 theme transmission 195:206 arg1 concern 159:165 a concern 157:165 a concern of potential human-to-human transmission 157:206 Avian influenza H7N9 virus has posed a concern of potential human-to-human transmission by resulting in seasonal virus-like human infection cases. 27613087 0 105 theme A 90:90 arg1 virus 98:102 avian influenza A(H7N9) virus 74:102 avian influenza A(H7N9) virus 74:102 Effects of HA and NA glycosylation pattern changes on the transmission of avian influenza A(H7N9) virus in guinea pigs. 27613087 5 106 from residue 951:957 arg1 removal 938:944 a removal 936:944 a removal from residue 42 or 66 936:966 Intriguingly, however, the NLG changes in the N9 NA protein, such as a removal from residue 42 or 66 or an addition at residue 266, increased transmissibility of the mutant viruses by more than 33%, 50%, and 16%, respectively, compared with a parental N9 virus. 27613087 5 106 from residue 951:957 arg1 addition 974:981 an addition 971:981 an addition at residue 266 971:996 Intriguingly, however, the NLG changes in the N9 NA protein, such as a removal from residue 42 or 66 or an addition at residue 266, increased transmissibility of the mutant viruses by more than 33%, 50%, and 16%, respectively, compared with a parental N9 virus. 27613087 2 107 theme virus 467:471 arg1 transmission 473:484 influenza virus transmission 457:484 influenza virus transmission 457:484 To address the issue of sustained human infection with the H7N9 virus, here we investigated the effects of hemagglutinin (HA) and neuraminidase (NA) N-linked glycosylation (NLG) patterns on influenza virus transmission in a guinea pig model. 27613087 3 108 theme H7N9 586:589 arg1 viruses 591:597 H7N9 viruses 586:597 H7N9 viruses 586:597 Based on the NLG signatures identified in the HA and NA genetic sequences of H7N9 viruses, we generated NLG mutant viruses using either HA or NA gene of a H7N9 virus, A/Anhui/01/2013, by reverse genetics on the 2009 pandemic H1N1 virus backbone. 27613087 2 109 theme human 301:305 arg1 infection 307:315 sustained human infection 291:315 sustained human infection with the H7N9 virus 291:335 To address the issue of sustained human infection with the H7N9 virus, here we investigated the effects of hemagglutinin (HA) and neuraminidase (NA) N-linked glycosylation (NLG) patterns on influenza virus transmission in a guinea pig model. 27613087 5 110 theme N9 1119:1120 arg1 virus 1122:1126 a parental N9 virus 1108:1126 a parental N9 virus 1108:1126 Intriguingly, however, the NLG changes in the N9 NA protein, such as a removal from residue 42 or 66 or an addition at residue 266, increased transmissibility of the mutant viruses by more than 33%, 50%, and 16%, respectively, compared with a parental N9 virus. 27613087 6 111 theme NLG 1231:1233 arg1 viruses 1242:1248 the HA-NA NLG mutant viruses 1221:1248 the HA-NA NLG mutant viruses harboring the H7 HA of double NLG addition and the N9 NA of various NLG patterns 1221:1329 Given the effects of HA-NA NLG changes with regard to viral transmission, we then generated the HA-NA NLG mutant viruses harboring the H7 HA of double NLG addition and the N9 NA of various NLG patterns. 27613087 1 112 theme human-to-human 180:193 arg1 transmission 195:206 potential human-to-human transmission 170:206 potential human-to-human transmission 170:206 Avian influenza H7N9 virus has posed a concern of potential human-to-human transmission by resulting in seasonal virus-like human infection cases. 27613087 6 113 theme NLG 1156:1158 arg1 changes 1160:1166 HA-NA NLG changes 1150:1166 HA-NA NLG changes with regard to viral transmission 1150:1200 Given the effects of HA-NA NLG changes with regard to viral transmission, we then generated the HA-NA NLG mutant viruses harboring the H7 HA of double NLG addition and the N9 NA of various NLG patterns. 27613087 2 114 theme H7N9 326:329 arg1 virus 331:335 the H7N9 virus 322:335 the H7N9 virus 322:335 To address the issue of sustained human infection with the H7N9 virus, here we investigated the effects of hemagglutinin (HA) and neuraminidase (NA) N-linked glycosylation (NLG) patterns on influenza virus transmission in a guinea pig model. 27052538 7 0 theme length 1162:1167 arg1 deficits 1132:1139 deficits 1132:1139 deficits of 36% weight and 9% length 1132:1167 RESULTS Undernourished mice completely recovered deficits of 36% weight and 9% length by 3 wk of refeeding, at which time they had 1.4-fold higher plasma phenyllactate and 2.0-fold higher urinary p-cresol sulfate concentrations than did controls. 27052538 4 1 from d 699:699 arg1 h 658:658 8 h 656:658 8 h at 6 d of age 656:672 METHODS Male and female CD1 mouse pups were undernourished by timed separation from lactating dams for 4 h at 5 d of age, 8 h at 6 d of age, and 12 h/d from 7 to 15 d of age, then resumed ad libitum nursing, whereas controls fed uninterrupted. 27052538 4 1 from d 699:699 arg1 h 639:639 4 h 637:639 4 h at 5 d of age 637:653 METHODS Male and female CD1 mouse pups were undernourished by timed separation from lactating dams for 4 h at 5 d of age, 8 h at 6 d of age, and 12 h/d from 7 to 15 d of age, then resumed ad libitum nursing, whereas controls fed uninterrupted. 27052538 4 1 from d 699:699 arg1 h/d 682:684 12 h/d 679:684 12 h/d from 7 to 15 d of age 679:706 METHODS Male and female CD1 mouse pups were undernourished by timed separation from lactating dams for 4 h at 5 d of age, 8 h at 6 d of age, and 12 h/d from 7 to 15 d of age, then resumed ad libitum nursing, whereas controls fed uninterrupted. 27052538 10 2 dep proportions 1757:1767 arg1 % 1786:1786 26% 1784:1786 26% compared with 16% 1784:1804 Microbiota profiles from undernourished mice also remained distinct, with lower mean proportions of Bacteroidetes (67% compared with 83%) and higher proportions of Firmicutes (26% compared with 16%). 27052538 8 3 from wk 1450:1451 arg1 controls 1436:1443 controls 1436:1443 controls at 3 wk 1436:1451 Plasma serotonin concentrations in undernourished mice were 25% lower at 0 wk but 1.5-fold higher than in controls at 3 wk. 27052538 12 4 theme community 1998:2006 arg1 0.015 2023:2027 P = 0.015 2019:2027 P = 0.015 2019:2027 Whereas microbiota from undernourished mice at 0 wk contained 11% less community diversity (P = 0.015), refed mice at 3 wk harbored 1.2-fold greater diversity (P = 0.0006) than did controls. 27052538 12 4 theme community 1998:2006 arg1 diversity 2008:2016 community diversity 1998:2016 community diversity (P = 0.015) 1998:2028 Whereas microbiota from undernourished mice at 0 wk contained 11% less community diversity (P = 0.015), refed mice at 3 wk harbored 1.2-fold greater diversity (P = 0.0006) than did controls. 27052538 0 5 theme Microbial-Derived 0:16 arg1 Metabolites 18:28 Microbial-Derived Metabolites 0:28 Microbial-Derived Metabolites 0:28 Microbial-Derived Metabolites Reflect an Altered Intestinal Microbiota during Catch-Up Growth in Undernourished Neonatal Mice. 27052538 9 6 theme multiple 1581:1588 arg1 glycans 1599:1605 multiple N-linked glycans 1581:1605 multiple N-linked glycans 1581:1605 Whereas most urine and plasma metabolites normalized with refeeding, 117 fecal metabolites remained altered at 3 wk, including multiple N-linked glycans. 27052538 12 7 from wk 2047:2048 arg1 mice 2037:2040 refed mice 2031:2040 refed mice at 3 wk 2031:2048 Whereas microbiota from undernourished mice at 0 wk contained 11% less community diversity (P = 0.015), refed mice at 3 wk harbored 1.2-fold greater diversity (P = 0.0006) than did controls. 27052538 1 8 theme obesity-related 230:244 arg1 disease 256:262 obesity-related metabolic disease 230:262 obesity-related metabolic disease 230:262 BACKGROUND Protein-energy undernutrition during early development confers a lifelong increased risk of obesity-related metabolic disease. 27052538 10 9 from mice 1648:1651 arg1 profiles 1619:1626 Microbiota profiles 1608:1626 Microbiota profiles from undernourished mice 1608:1651 Microbiota profiles from undernourished mice also remained distinct, with lower mean proportions of Bacteroidetes (67% compared with 83%) and higher proportions of Firmicutes (26% compared with 16%). 27052538 6 10 theme sequencing 1071:1080 arg1 use 1048:1050 the use 1044:1050 the use of 16S metagenomic sequencing 1044:1080 At 3 time points (0, 1, and 3 wk after ending feed deprivation), metabolites in urine, plasma, and stool were identified with the use of mass spectrometry, and fecal microbes were identified with the use of 16S metagenomic sequencing. 27052538 10 11 theme lower 1682:1686 arg1 proportions 1693:1703 lower mean proportions 1682:1703 lower mean proportions of Bacteroidetes (67% compared with 83%) and higher proportions of Firmicutes (26% compared with 16%) 1682:1805 Microbiota profiles from undernourished mice also remained distinct, with lower mean proportions of Bacteroidetes (67% compared with 83%) and higher proportions of Firmicutes (26% compared with 16%). 27052538 8 12 from concentrations 1347:1360 arg1 mice 1380:1383 undernourished mice 1365:1383 undernourished mice 1365:1383 Plasma serotonin concentrations in undernourished mice were 25% lower at 0 wk but 1.5-fold higher than in controls at 3 wk. 27052538 1 13 theme disease 256:262 arg1 risk 222:225 a lifelong increased risk 201:225 a lifelong increased risk of obesity-related metabolic disease 201:262 BACKGROUND Protein-energy undernutrition during early development confers a lifelong increased risk of obesity-related metabolic disease. 27052538 7 14 theme higher 1223:1228 arg1 phenyllactate 1237:1249 1.4-fold higher plasma phenyllactate 1214:1249 1.4-fold higher plasma phenyllactate 1214:1249 RESULTS Undernourished mice completely recovered deficits of 36% weight and 9% length by 3 wk of refeeding, at which time they had 1.4-fold higher plasma phenyllactate and 2.0-fold higher urinary p-cresol sulfate concentrations than did controls. 27052538 7 15 contain had 1210:1212 arg1 they 1205:1208 they 1205:1208 they 1205:1208 RESULTS Undernourished mice completely recovered deficits of 36% weight and 9% length by 3 wk of refeeding, at which time they had 1.4-fold higher plasma phenyllactate and 2.0-fold higher urinary p-cresol sulfate concentrations than did controls. 27052538 7 15 contain had 1210:1212 arg2 phenyllactate 1237:1249 1.4-fold higher plasma phenyllactate 1214:1249 1.4-fold higher plasma phenyllactate 1214:1249 RESULTS Undernourished mice completely recovered deficits of 36% weight and 9% length by 3 wk of refeeding, at which time they had 1.4-fold higher plasma phenyllactate and 2.0-fold higher urinary p-cresol sulfate concentrations than did controls. 27052538 7 15 contain had 1210:1212 arg2 concentrations 1296:1309 2.0-fold higher urinary p-cresol sulfate concentrations 1255:1309 2.0-fold higher urinary p-cresol sulfate concentrations 1255:1309 RESULTS Undernourished mice completely recovered deficits of 36% weight and 9% length by 3 wk of refeeding, at which time they had 1.4-fold higher plasma phenyllactate and 2.0-fold higher urinary p-cresol sulfate concentrations than did controls. 27052538 2 16 theme metabolic 285:293 arg1 abnormalities 295:307 metabolic abnormalities 285:307 metabolic abnormalities 285:307 Mechanisms by which metabolic abnormalities persist despite catch-up growth are poorly understood. 27052538 13 17 theme intestinal 2163:2172 arg1 microbiota 2174:2183 intestinal microbiota 2163:2183 intestinal microbiota 2163:2183 CONCLUSION Microbial-derived metabolites and intestinal microbiota remain altered during catch-up growth in undernourished neonatal mice. 27052538 4 18 theme CD1 558:560 arg1 pups 568:571 Male and female CD1 mouse pups 542:571 Male and female CD1 mouse pups 542:571 METHODS Male and female CD1 mouse pups were undernourished by timed separation from lactating dams for 4 h at 5 d of age, 8 h at 6 d of age, and 12 h/d from 7 to 15 d of age, then resumed ad libitum nursing, whereas controls fed uninterrupted. 27052538 7 19 theme p-cresol 1279:1286 arg1 concentrations 1296:1309 2.0-fold higher urinary p-cresol sulfate concentrations 1255:1309 2.0-fold higher urinary p-cresol sulfate concentrations 1255:1309 RESULTS Undernourished mice completely recovered deficits of 36% weight and 9% length by 3 wk of refeeding, at which time they had 1.4-fold higher plasma phenyllactate and 2.0-fold higher urinary p-cresol sulfate concentrations than did controls. 27052538 10 20 theme Bacteroidetes 1708:1720 arg1 proportions 1693:1703 lower mean proportions 1682:1703 lower mean proportions of Bacteroidetes (67% compared with 83%) and higher proportions of Firmicutes (26% compared with 16%) 1682:1805 Microbiota profiles from undernourished mice also remained distinct, with lower mean proportions of Bacteroidetes (67% compared with 83%) and higher proportions of Firmicutes (26% compared with 16%). 27052538 12 21 from mice 1966:1969 arg1 microbiota 1935:1944 microbiota 1935:1944 microbiota from undernourished mice at 0 wk 1935:1977 Whereas microbiota from undernourished mice at 0 wk contained 11% less community diversity (P = 0.015), refed mice at 3 wk harbored 1.2-fold greater diversity (P = 0.0006) than did controls. 27052538 6 22 theme ending 887:892 arg1 deprivation 899:909 ending feed deprivation 887:909 ending feed deprivation 887:909 At 3 time points (0, 1, and 3 wk after ending feed deprivation), metabolites in urine, plasma, and stool were identified with the use of mass spectrometry, and fecal microbes were identified with the use of 16S metagenomic sequencing. 27052538 7 23 theme higher 1264:1269 arg1 concentrations 1296:1309 2.0-fold higher urinary p-cresol sulfate concentrations 1255:1309 2.0-fold higher urinary p-cresol sulfate concentrations 1255:1309 RESULTS Undernourished mice completely recovered deficits of 36% weight and 9% length by 3 wk of refeeding, at which time they had 1.4-fold higher plasma phenyllactate and 2.0-fold higher urinary p-cresol sulfate concentrations than did controls. 27052538 2 24 theme catch-up 325:332 arg1 growth 334:339 catch-up growth 325:339 catch-up growth 325:339 Mechanisms by which metabolic abnormalities persist despite catch-up growth are poorly understood. 27052538 1 25 theme early 175:179 arg1 development 181:191 early development 175:191 early development 175:191 BACKGROUND Protein-energy undernutrition during early development confers a lifelong increased risk of obesity-related metabolic disease. 27052538 3 26 theme abnormal 405:412 arg1 profiles 452:459 abnormal metabolomic and intestinal microbiota profiles 405:459 abnormal metabolomic and intestinal microbiota profiles from undernourished neonatal mice 405:493 OBJECTIVE We sought to determine whether abnormal metabolomic and intestinal microbiota profiles from undernourished neonatal mice remain altered during catch-up growth. 27052538 0 27 theme Catch-Up 78:85 arg1 Growth 87:92 Catch-Up Growth 78:92 Catch-Up Growth in Undernourished Neonatal Mice 78:124 Microbial-Derived Metabolites Reflect an Altered Intestinal Microbiota during Catch-Up Growth in Undernourished Neonatal Mice. 27052538 3 28 theme catch-up 517:524 arg1 growth 526:531 catch-up growth 517:531 catch-up growth 517:531 OBJECTIVE We sought to determine whether abnormal metabolomic and intestinal microbiota profiles from undernourished neonatal mice remain altered during catch-up growth. 27052538 4 29 theme timed 596:600 arg1 separation 602:611 timed separation 596:611 timed separation from lactating dams 596:631 METHODS Male and female CD1 mouse pups were undernourished by timed separation from lactating dams for 4 h at 5 d of age, 8 h at 6 d of age, and 12 h/d from 7 to 15 d of age, then resumed ad libitum nursing, whereas controls fed uninterrupted. 27052538 4 30 theme age 704:706 arg1 h 658:658 8 h 656:658 8 h at 6 d of age 656:672 METHODS Male and female CD1 mouse pups were undernourished by timed separation from lactating dams for 4 h at 5 d of age, 8 h at 6 d of age, and 12 h/d from 7 to 15 d of age, then resumed ad libitum nursing, whereas controls fed uninterrupted. 27052538 4 30 theme age 704:706 arg1 h 639:639 4 h 637:639 4 h at 5 d of age 637:653 METHODS Male and female CD1 mouse pups were undernourished by timed separation from lactating dams for 4 h at 5 d of age, 8 h at 6 d of age, and 12 h/d from 7 to 15 d of age, then resumed ad libitum nursing, whereas controls fed uninterrupted. 27052538 4 30 theme age 704:706 arg1 h/d 682:684 12 h/d 679:684 12 h/d from 7 to 15 d of age 679:706 METHODS Male and female CD1 mouse pups were undernourished by timed separation from lactating dams for 4 h at 5 d of age, 8 h at 6 d of age, and 12 h/d from 7 to 15 d of age, then resumed ad libitum nursing, whereas controls fed uninterrupted. 27052538 3 31 theme microbiota 441:450 arg1 profiles 452:459 abnormal metabolomic and intestinal microbiota profiles 405:459 abnormal metabolomic and intestinal microbiota profiles from undernourished neonatal mice 405:493 OBJECTIVE We sought to determine whether abnormal metabolomic and intestinal microbiota profiles from undernourished neonatal mice remain altered during catch-up growth. 27052538 13 32 link Microbial-derived 2129:2145 arg1 metabolites 2147:2157 Microbial-derived metabolites 2129:2157 Microbial-derived metabolites 2129:2157 CONCLUSION Microbial-derived metabolites and intestinal microbiota remain altered during catch-up growth in undernourished neonatal mice. 27052538 0 33 theme Neonatal 112:119 arg1 Mice 121:124 Undernourished Neonatal Mice 97:124 Undernourished Neonatal Mice 97:124 Microbial-Derived Metabolites Reflect an Altered Intestinal Microbiota during Catch-Up Growth in Undernourished Neonatal Mice. 27052538 12 34 theme = 2089:2089 arg1 diversity 2076:2084 1.2-fold greater diversity 2059:2084 1.2-fold greater diversity (P = 0.0006) than did controls 2059:2115 Whereas microbiota from undernourished mice at 0 wk contained 11% less community diversity (P = 0.015), refed mice at 3 wk harbored 1.2-fold greater diversity (P = 0.0006) than did controls. 27052538 12 34 theme = 2089:2089 arg1 P 2087:2087 P = 0.0006 2087:2096 P = 0.0006 2087:2096 Whereas microbiota from undernourished mice at 0 wk contained 11% less community diversity (P = 0.015), refed mice at 3 wk harbored 1.2-fold greater diversity (P = 0.0006) than did controls. 27052538 4 35 dep 15 696:697 arg1 to 693:694 to 693:694 to 693:694 METHODS Male and female CD1 mouse pups were undernourished by timed separation from lactating dams for 4 h at 5 d of age, 8 h at 6 d of age, and 12 h/d from 7 to 15 d of age, then resumed ad libitum nursing, whereas controls fed uninterrupted. 27052538 9 36 link N-linked 1590:1597 arg1 glycans 1599:1605 multiple N-linked glycans 1581:1605 multiple N-linked glycans 1581:1605 Whereas most urine and plasma metabolites normalized with refeeding, 117 fecal metabolites remained altered at 3 wk, including multiple N-linked glycans. 27052538 3 37 theme neonatal 481:488 arg1 mice 490:493 undernourished neonatal mice 466:493 undernourished neonatal mice 466:493 OBJECTIVE We sought to determine whether abnormal metabolomic and intestinal microbiota profiles from undernourished neonatal mice remain altered during catch-up growth. 27052538 13 38 from growth 2216:2221 arg1 mice 2250:2253 undernourished neonatal mice 2226:2253 undernourished neonatal mice 2226:2253 CONCLUSION Microbial-derived metabolites and intestinal microbiota remain altered during catch-up growth in undernourished neonatal mice. 27052538 4 39 from d 646:646 arg1 h 658:658 8 h 656:658 8 h at 6 d of age 656:672 METHODS Male and female CD1 mouse pups were undernourished by timed separation from lactating dams for 4 h at 5 d of age, 8 h at 6 d of age, and 12 h/d from 7 to 15 d of age, then resumed ad libitum nursing, whereas controls fed uninterrupted. 27052538 4 39 from d 646:646 arg1 h 639:639 4 h 637:639 4 h at 5 d of age 637:653 METHODS Male and female CD1 mouse pups were undernourished by timed separation from lactating dams for 4 h at 5 d of age, 8 h at 6 d of age, and 12 h/d from 7 to 15 d of age, then resumed ad libitum nursing, whereas controls fed uninterrupted. 27052538 4 39 from d 646:646 arg1 h/d 682:684 12 h/d 679:684 12 h/d from 7 to 15 d of age 679:706 METHODS Male and female CD1 mouse pups were undernourished by timed separation from lactating dams for 4 h at 5 d of age, 8 h at 6 d of age, and 12 h/d from 7 to 15 d of age, then resumed ad libitum nursing, whereas controls fed uninterrupted. 27052538 4 40 dep resumed 714:720 arg1 whereas 742:748 whereas 742:748 whereas 742:748 METHODS Male and female CD1 mouse pups were undernourished by timed separation from lactating dams for 4 h at 5 d of age, 8 h at 6 d of age, and 12 h/d from 7 to 15 d of age, then resumed ad libitum nursing, whereas controls fed uninterrupted. 27052538 6 41 theme spectrometry 990:1001 arg1 use 978:980 the use 974:980 the use of mass spectrometry 974:1001 At 3 time points (0, 1, and 3 wk after ending feed deprivation), metabolites in urine, plasma, and stool were identified with the use of mass spectrometry, and fecal microbes were identified with the use of 16S metagenomic sequencing. 27052538 6 42 from metabolites 913:923 arg1 plasma 935:940 plasma 935:940 plasma 935:940 At 3 time points (0, 1, and 3 wk after ending feed deprivation), metabolites in urine, plasma, and stool were identified with the use of mass spectrometry, and fecal microbes were identified with the use of 16S metagenomic sequencing. 27052538 6 42 from metabolites 913:923 arg1 stool 947:951 stool 947:951 stool 947:951 At 3 time points (0, 1, and 3 wk after ending feed deprivation), metabolites in urine, plasma, and stool were identified with the use of mass spectrometry, and fecal microbes were identified with the use of 16S metagenomic sequencing. 27052538 6 42 from metabolites 913:923 arg1 urine 928:932 urine 928:932 urine 928:932 At 3 time points (0, 1, and 3 wk after ending feed deprivation), metabolites in urine, plasma, and stool were identified with the use of mass spectrometry, and fecal microbes were identified with the use of 16S metagenomic sequencing. 27052538 12 43 theme 1.2-fold 2059:2066 arg1 diversity 2076:2084 1.2-fold greater diversity 2059:2084 1.2-fold greater diversity (P = 0.0006) than did controls 2059:2115 Whereas microbiota from undernourished mice at 0 wk contained 11% less community diversity (P = 0.015), refed mice at 3 wk harbored 1.2-fold greater diversity (P = 0.0006) than did controls. 27052538 12 43 theme 1.2-fold 2059:2066 arg1 P 2087:2087 P = 0.0006 2087:2096 P = 0.0006 2087:2096 Whereas microbiota from undernourished mice at 0 wk contained 11% less community diversity (P = 0.015), refed mice at 3 wk harbored 1.2-fold greater diversity (P = 0.0006) than did controls. 27052538 5 44 theme standard 822:829 arg1 diet 842:845 a standard unpurified diet 820:845 a standard unpurified diet 820:845 Both groups were weaned simultaneously to a standard unpurified diet. 27052538 1 45 theme BACKGROUND 127:136 arg1 undernutrition 153:166 BACKGROUND Protein-energy undernutrition 127:166 BACKGROUND Protein-energy undernutrition during early development 127:191 BACKGROUND Protein-energy undernutrition during early development confers a lifelong increased risk of obesity-related metabolic disease. 27052538 10 46 theme higher 1750:1755 arg1 proportions 1757:1767 higher proportions 1750:1767 higher proportions of Firmicutes (26% compared with 16%) 1750:1805 Microbiota profiles from undernourished mice also remained distinct, with lower mean proportions of Bacteroidetes (67% compared with 83%) and higher proportions of Firmicutes (26% compared with 16%). 27052538 12 47 theme refed 2031:2035 arg1 mice 2037:2040 refed mice 2031:2040 refed mice at 3 wk 2031:2048 Whereas microbiota from undernourished mice at 0 wk contained 11% less community diversity (P = 0.015), refed mice at 3 wk harbored 1.2-fold greater diversity (P = 0.0006) than did controls. 27052538 7 48 theme RESULTS 1083:1089 arg1 mice 1106:1109 RESULTS Undernourished mice 1083:1109 RESULTS Undernourished mice 1083:1109 RESULTS Undernourished mice completely recovered deficits of 36% weight and 9% length by 3 wk of refeeding, at which time they had 1.4-fold higher plasma phenyllactate and 2.0-fold higher urinary p-cresol sulfate concentrations than did controls. 27052538 0 49 theme Altered 41:47 arg1 Microbiota 60:69 an Altered Intestinal Microbiota 38:69 an Altered Intestinal Microbiota 38:69 Microbial-Derived Metabolites Reflect an Altered Intestinal Microbiota during Catch-Up Growth in Undernourished Neonatal Mice. 27052538 6 50 theme time 853:856 arg1 points 858:863 3 time points 851:863 3 time points (0, 1, and 3 wk after ending feed deprivation) 851:910 At 3 time points (0, 1, and 3 wk after ending feed deprivation), metabolites in urine, plasma, and stool were identified with the use of mass spectrometry, and fecal microbes were identified with the use of 16S metagenomic sequencing. 27052538 4 51 from d 665:665 arg1 h 658:658 8 h 656:658 8 h at 6 d of age 656:672 METHODS Male and female CD1 mouse pups were undernourished by timed separation from lactating dams for 4 h at 5 d of age, 8 h at 6 d of age, and 12 h/d from 7 to 15 d of age, then resumed ad libitum nursing, whereas controls fed uninterrupted. 27052538 4 51 from d 665:665 arg1 h 639:639 4 h 637:639 4 h at 5 d of age 637:653 METHODS Male and female CD1 mouse pups were undernourished by timed separation from lactating dams for 4 h at 5 d of age, 8 h at 6 d of age, and 12 h/d from 7 to 15 d of age, then resumed ad libitum nursing, whereas controls fed uninterrupted. 27052538 4 51 from d 665:665 arg1 h/d 682:684 12 h/d 679:684 12 h/d from 7 to 15 d of age 679:706 METHODS Male and female CD1 mouse pups were undernourished by timed separation from lactating dams for 4 h at 5 d of age, 8 h at 6 d of age, and 12 h/d from 7 to 15 d of age, then resumed ad libitum nursing, whereas controls fed uninterrupted. 27052538 8 52 theme Plasma 1330:1335 arg1 concentrations 1347:1360 Plasma serotonin concentrations 1330:1360 Plasma serotonin concentrations in undernourished mice 1330:1383 Plasma serotonin concentrations in undernourished mice were 25% lower at 0 wk but 1.5-fold higher than in controls at 3 wk. 27052538 4 53 from dams 628:631 arg1 separation 602:611 timed separation 596:611 timed separation from lactating dams 596:631 METHODS Male and female CD1 mouse pups were undernourished by timed separation from lactating dams for 4 h at 5 d of age, 8 h at 6 d of age, and 12 h/d from 7 to 15 d of age, then resumed ad libitum nursing, whereas controls fed uninterrupted. 27052538 6 54 dep points 858:863 arg1 wk 878:879 0, 1, and 3 wk 866:879 0, 1, and 3 wk after ending feed deprivation 866:909 At 3 time points (0, 1, and 3 wk after ending feed deprivation), metabolites in urine, plasma, and stool were identified with the use of mass spectrometry, and fecal microbes were identified with the use of 16S metagenomic sequencing. 27052538 12 55 theme = 2021:2021 arg1 0.015 2023:2027 P = 0.015 2019:2027 P = 0.015 2019:2027 Whereas microbiota from undernourished mice at 0 wk contained 11% less community diversity (P = 0.015), refed mice at 3 wk harbored 1.2-fold greater diversity (P = 0.0006) than did controls. 27052538 12 55 theme = 2021:2021 arg1 diversity 2008:2016 community diversity 1998:2016 community diversity (P = 0.015) 1998:2028 Whereas microbiota from undernourished mice at 0 wk contained 11% less community diversity (P = 0.015), refed mice at 3 wk harbored 1.2-fold greater diversity (P = 0.0006) than did controls. 27052538 9 56 theme fecal 1527:1531 arg1 metabolites 1533:1543 117 fecal metabolites 1523:1543 117 fecal metabolites 1523:1543 Whereas most urine and plasma metabolites normalized with refeeding, 117 fecal metabolites remained altered at 3 wk, including multiple N-linked glycans. 27052538 7 57 theme refeeding 1180:1188 arg1 wk 1174:1175 3 wk 1172:1175 3 wk of refeeding, at which time they had 1.4-fold higher plasma phenyllactate and 2.0-fold higher urinary p-cresol sulfate concentrations than did controls 1172:1327 RESULTS Undernourished mice completely recovered deficits of 36% weight and 9% length by 3 wk of refeeding, at which time they had 1.4-fold higher plasma phenyllactate and 2.0-fold higher urinary p-cresol sulfate concentrations than did controls. 27052538 8 58 theme undernourished 1365:1378 arg1 mice 1380:1383 undernourished mice 1365:1383 undernourished mice 1365:1383 Plasma serotonin concentrations in undernourished mice were 25% lower at 0 wk but 1.5-fold higher than in controls at 3 wk. 27052538 13 59 theme undernourished 2226:2239 arg1 mice 2250:2253 undernourished neonatal mice 2226:2253 undernourished neonatal mice 2226:2253 CONCLUSION Microbial-derived metabolites and intestinal microbiota remain altered during catch-up growth in undernourished neonatal mice. 27052538 7 60 theme weight 1148:1153 arg1 deficits 1132:1139 deficits 1132:1139 deficits of 36% weight and 9% length 1132:1167 RESULTS Undernourished mice completely recovered deficits of 36% weight and 9% length by 3 wk of refeeding, at which time they had 1.4-fold higher plasma phenyllactate and 2.0-fold higher urinary p-cresol sulfate concentrations than did controls. 27052538 10 61 theme undernourished 1633:1646 arg1 mice 1648:1651 undernourished mice 1633:1651 undernourished mice 1633:1651 Microbiota profiles from undernourished mice also remained distinct, with lower mean proportions of Bacteroidetes (67% compared with 83%) and higher proportions of Firmicutes (26% compared with 16%). 27052538 4 62 theme age 651:653 arg1 d 646:646 5 d 644:646 5 d of age 644:653 METHODS Male and female CD1 mouse pups were undernourished by timed separation from lactating dams for 4 h at 5 d of age, 8 h at 6 d of age, and 12 h/d from 7 to 15 d of age, then resumed ad libitum nursing, whereas controls fed uninterrupted. 27052538 3 63 dep OBJECTIVE 364:372 arg1 sought 377:382 sought 377:382 sought to determine whether abnormal metabolomic and intestinal microbiota profiles from undernourished neonatal mice remain altered during catch-up growth 377:531 OBJECTIVE We sought to determine whether abnormal metabolomic and intestinal microbiota profiles from undernourished neonatal mice remain altered during catch-up growth. 27052538 12 64 contain contained 1979:1987 arg1 microbiota 1935:1944 microbiota 1935:1944 microbiota from undernourished mice at 0 wk 1935:1977 Whereas microbiota from undernourished mice at 0 wk contained 11% less community diversity (P = 0.015), refed mice at 3 wk harbored 1.2-fold greater diversity (P = 0.0006) than did controls. 27052538 12 64 contain contained 1979:1987 arg2 diversity 2008:2016 community diversity 1998:2016 community diversity (P = 0.015) 1998:2028 Whereas microbiota from undernourished mice at 0 wk contained 11% less community diversity (P = 0.015), refed mice at 3 wk harbored 1.2-fold greater diversity (P = 0.0006) than did controls. 27052538 12 64 contain contained 1979:1987 arg2 % 1991:1991 11% 1989:1991 11% 1989:1991 Whereas microbiota from undernourished mice at 0 wk contained 11% less community diversity (P = 0.015), refed mice at 3 wk harbored 1.2-fold greater diversity (P = 0.0006) than did controls. 27052538 12 64 contain contained 1979:1987 arg2 0.015 2023:2027 P = 0.015 2019:2027 P = 0.015 2019:2027 Whereas microbiota from undernourished mice at 0 wk contained 11% less community diversity (P = 0.015), refed mice at 3 wk harbored 1.2-fold greater diversity (P = 0.0006) than did controls. 27052538 1 65 theme increased 212:220 arg1 risk 222:225 a lifelong increased risk 201:225 a lifelong increased risk of obesity-related metabolic disease 201:262 BACKGROUND Protein-energy undernutrition during early development confers a lifelong increased risk of obesity-related metabolic disease. 27052538 9 66 theme N-linked 1590:1597 arg1 glycans 1599:1605 multiple N-linked glycans 1581:1605 multiple N-linked glycans 1581:1605 Whereas most urine and plasma metabolites normalized with refeeding, 117 fecal metabolites remained altered at 3 wk, including multiple N-linked glycans. 27052538 10 67 theme mean 1688:1691 arg1 proportions 1693:1703 lower mean proportions 1682:1703 lower mean proportions of Bacteroidetes (67% compared with 83%) and higher proportions of Firmicutes (26% compared with 16%) 1682:1805 Microbiota profiles from undernourished mice also remained distinct, with lower mean proportions of Bacteroidetes (67% compared with 83%) and higher proportions of Firmicutes (26% compared with 16%). 27052538 1 68 theme metabolic 246:254 arg1 disease 256:262 obesity-related metabolic disease 230:262 obesity-related metabolic disease 230:262 BACKGROUND Protein-energy undernutrition during early development confers a lifelong increased risk of obesity-related metabolic disease. 27052538 4 69 theme female 551:556 arg1 pups 568:571 Male and female CD1 mouse pups 542:571 Male and female CD1 mouse pups 542:571 METHODS Male and female CD1 mouse pups were undernourished by timed separation from lactating dams for 4 h at 5 d of age, 8 h at 6 d of age, and 12 h/d from 7 to 15 d of age, then resumed ad libitum nursing, whereas controls fed uninterrupted. 27052538 6 70 theme metagenomic 1059:1069 arg1 sequencing 1071:1080 16S metagenomic sequencing 1055:1080 16S metagenomic sequencing 1055:1080 At 3 time points (0, 1, and 3 wk after ending feed deprivation), metabolites in urine, plasma, and stool were identified with the use of mass spectrometry, and fecal microbes were identified with the use of 16S metagenomic sequencing. 27052538 4 71 theme age 670:672 arg1 d 665:665 6 d 663:665 6 d of age 663:672 METHODS Male and female CD1 mouse pups were undernourished by timed separation from lactating dams for 4 h at 5 d of age, 8 h at 6 d of age, and 12 h/d from 7 to 15 d of age, then resumed ad libitum nursing, whereas controls fed uninterrupted. 27052538 10 72 theme Microbiota 1608:1617 arg1 profiles 1619:1626 Microbiota profiles 1608:1626 Microbiota profiles from undernourished mice 1608:1651 Microbiota profiles from undernourished mice also remained distinct, with lower mean proportions of Bacteroidetes (67% compared with 83%) and higher proportions of Firmicutes (26% compared with 16%). 27052538 11 73 theme mucolytic 1826:1834 arg1 organisms 1836:1844 the mucolytic organisms 1822:1844 the mucolytic organisms 1822:1844 Abundances of the mucolytic organisms Akkermansia muciniphila and Mucispirillum schaedleri were altered at 0 and 1 wk. 27052538 0 74 from Growth 87:92 arg1 Mice 121:124 Undernourished Neonatal Mice 97:124 Undernourished Neonatal Mice 97:124 Microbial-Derived Metabolites Reflect an Altered Intestinal Microbiota during Catch-Up Growth in Undernourished Neonatal Mice. 27052538 1 75 theme Protein-energy 138:151 arg1 undernutrition 153:166 BACKGROUND Protein-energy undernutrition 127:166 BACKGROUND Protein-energy undernutrition during early development 127:191 BACKGROUND Protein-energy undernutrition during early development confers a lifelong increased risk of obesity-related metabolic disease. 27052538 6 76 theme feed 894:897 arg1 deprivation 899:909 ending feed deprivation 887:909 ending feed deprivation 887:909 At 3 time points (0, 1, and 3 wk after ending feed deprivation), metabolites in urine, plasma, and stool were identified with the use of mass spectrometry, and fecal microbes were identified with the use of 16S metagenomic sequencing. 27052538 7 77 theme sulfate 1288:1294 arg1 concentrations 1296:1309 2.0-fold higher urinary p-cresol sulfate concentrations 1255:1309 2.0-fold higher urinary p-cresol sulfate concentrations 1255:1309 RESULTS Undernourished mice completely recovered deficits of 36% weight and 9% length by 3 wk of refeeding, at which time they had 1.4-fold higher plasma phenyllactate and 2.0-fold higher urinary p-cresol sulfate concentrations than did controls. 27052538 12 78 theme undernourished 1951:1964 arg1 mice 1966:1969 undernourished mice 1951:1969 undernourished mice 1951:1969 Whereas microbiota from undernourished mice at 0 wk contained 11% less community diversity (P = 0.015), refed mice at 3 wk harbored 1.2-fold greater diversity (P = 0.0006) than did controls. 27052538 4 79 theme Male 542:545 arg1 pups 568:571 Male and female CD1 mouse pups 542:571 Male and female CD1 mouse pups 542:571 METHODS Male and female CD1 mouse pups were undernourished by timed separation from lactating dams for 4 h at 5 d of age, 8 h at 6 d of age, and 12 h/d from 7 to 15 d of age, then resumed ad libitum nursing, whereas controls fed uninterrupted. 27052538 7 80 theme urinary 1271:1277 arg1 concentrations 1296:1309 2.0-fold higher urinary p-cresol sulfate concentrations 1255:1309 2.0-fold higher urinary p-cresol sulfate concentrations 1255:1309 RESULTS Undernourished mice completely recovered deficits of 36% weight and 9% length by 3 wk of refeeding, at which time they had 1.4-fold higher plasma phenyllactate and 2.0-fold higher urinary p-cresol sulfate concentrations than did controls. 27052538 7 81 theme 9 1159:1159 arg1 % 1160:1160 % 1160:1160 % 1160:1160 RESULTS Undernourished mice completely recovered deficits of 36% weight and 9% length by 3 wk of refeeding, at which time they had 1.4-fold higher plasma phenyllactate and 2.0-fold higher urinary p-cresol sulfate concentrations than did controls. 27052538 5 82 theme unpurified 831:840 arg1 diet 842:845 a standard unpurified diet 820:845 a standard unpurified diet 820:845 Both groups were weaned simultaneously to a standard unpurified diet. 27052538 7 83 dep did 1316:1318 arg1 than 1311:1314 than 1311:1314 than 1311:1314 RESULTS Undernourished mice completely recovered deficits of 36% weight and 9% length by 3 wk of refeeding, at which time they had 1.4-fold higher plasma phenyllactate and 2.0-fold higher urinary p-cresol sulfate concentrations than did controls. 27052538 3 84 theme metabolomic 414:424 arg1 profiles 452:459 abnormal metabolomic and intestinal microbiota profiles 405:459 abnormal metabolomic and intestinal microbiota profiles from undernourished neonatal mice 405:493 OBJECTIVE We sought to determine whether abnormal metabolomic and intestinal microbiota profiles from undernourished neonatal mice remain altered during catch-up growth. 27052538 7 85 theme % 1146:1146 arg1 weight 1148:1153 36% weight 1144:1153 36% weight 1144:1153 RESULTS Undernourished mice completely recovered deficits of 36% weight and 9% length by 3 wk of refeeding, at which time they had 1.4-fold higher plasma phenyllactate and 2.0-fold higher urinary p-cresol sulfate concentrations than did controls. 27052538 0 86 theme Undernourished 97:110 arg1 Mice 121:124 Undernourished Neonatal Mice 97:124 Undernourished Neonatal Mice 97:124 Microbial-Derived Metabolites Reflect an Altered Intestinal Microbiota during Catch-Up Growth in Undernourished Neonatal Mice. 27052538 12 87 dep diversity 2076:2084 arg1 did 2104:2106 did 2104:2106 did 2104:2106 Whereas microbiota from undernourished mice at 0 wk contained 11% less community diversity (P = 0.015), refed mice at 3 wk harbored 1.2-fold greater diversity (P = 0.0006) than did controls. 27052538 4 88 theme lactating 618:626 arg1 dams 628:631 lactating dams 618:631 lactating dams 618:631 METHODS Male and female CD1 mouse pups were undernourished by timed separation from lactating dams for 4 h at 5 d of age, 8 h at 6 d of age, and 12 h/d from 7 to 15 d of age, then resumed ad libitum nursing, whereas controls fed uninterrupted. 27052538 7 89 theme 36 1144:1145 arg1 % 1146:1146 % 1146:1146 % 1146:1146 RESULTS Undernourished mice completely recovered deficits of 36% weight and 9% length by 3 wk of refeeding, at which time they had 1.4-fold higher plasma phenyllactate and 2.0-fold higher urinary p-cresol sulfate concentrations than did controls. 27052538 12 90 theme P 2019:2019 arg1 0.015 2023:2027 P = 0.015 2019:2027 P = 0.015 2019:2027 Whereas microbiota from undernourished mice at 0 wk contained 11% less community diversity (P = 0.015), refed mice at 3 wk harbored 1.2-fold greater diversity (P = 0.0006) than did controls. 27052538 12 90 theme P 2019:2019 arg1 diversity 2008:2016 community diversity 1998:2016 community diversity (P = 0.015) 1998:2028 Whereas microbiota from undernourished mice at 0 wk contained 11% less community diversity (P = 0.015), refed mice at 3 wk harbored 1.2-fold greater diversity (P = 0.0006) than did controls. 27052538 13 91 theme Microbial-derived 2129:2145 arg1 metabolites 2147:2157 Microbial-derived metabolites 2129:2157 Microbial-derived metabolites 2129:2157 CONCLUSION Microbial-derived metabolites and intestinal microbiota remain altered during catch-up growth in undernourished neonatal mice. 27052538 13 92 dep CONCLUSION 2118:2127 arg1 metabolites 2147:2157 Microbial-derived metabolites 2129:2157 Microbial-derived metabolites 2129:2157 CONCLUSION Microbial-derived metabolites and intestinal microbiota remain altered during catch-up growth in undernourished neonatal mice. 27052538 12 93 theme greater 2068:2074 arg1 diversity 2076:2084 1.2-fold greater diversity 2059:2084 1.2-fold greater diversity (P = 0.0006) than did controls 2059:2115 Whereas microbiota from undernourished mice at 0 wk contained 11% less community diversity (P = 0.015), refed mice at 3 wk harbored 1.2-fold greater diversity (P = 0.0006) than did controls. 27052538 12 93 theme greater 2068:2074 arg1 P 2087:2087 P = 0.0006 2087:2096 P = 0.0006 2087:2096 Whereas microbiota from undernourished mice at 0 wk contained 11% less community diversity (P = 0.015), refed mice at 3 wk harbored 1.2-fold greater diversity (P = 0.0006) than did controls. 27052538 10 94 dep Bacteroidetes 1708:1720 arg1 % 1725:1725 67% 1723:1725 67% compared with 83% 1723:1743 Microbiota profiles from undernourished mice also remained distinct, with lower mean proportions of Bacteroidetes (67% compared with 83%) and higher proportions of Firmicutes (26% compared with 16%). 27052538 7 95 theme plasma 1230:1235 arg1 phenyllactate 1237:1249 1.4-fold higher plasma phenyllactate 1214:1249 1.4-fold higher plasma phenyllactate 1214:1249 RESULTS Undernourished mice completely recovered deficits of 36% weight and 9% length by 3 wk of refeeding, at which time they had 1.4-fold higher plasma phenyllactate and 2.0-fold higher urinary p-cresol sulfate concentrations than did controls. 27052538 3 96 theme intestinal 430:439 arg1 profiles 452:459 abnormal metabolomic and intestinal microbiota profiles 405:459 abnormal metabolomic and intestinal microbiota profiles from undernourished neonatal mice 405:493 OBJECTIVE We sought to determine whether abnormal metabolomic and intestinal microbiota profiles from undernourished neonatal mice remain altered during catch-up growth. 27052538 3 97 from mice 490:493 arg1 profiles 452:459 abnormal metabolomic and intestinal microbiota profiles 405:459 abnormal metabolomic and intestinal microbiota profiles from undernourished neonatal mice 405:493 OBJECTIVE We sought to determine whether abnormal metabolomic and intestinal microbiota profiles from undernourished neonatal mice remain altered during catch-up growth. 27052538 9 98 theme urine 1467:1471 arg1 metabolites 1484:1494 Whereas most urine and plasma metabolites 1454:1494 Whereas most urine and plasma metabolites 1454:1494 Whereas most urine and plasma metabolites normalized with refeeding, 117 fecal metabolites remained altered at 3 wk, including multiple N-linked glycans. 27052538 7 99 theme Undernourished 1091:1104 arg1 mice 1106:1109 RESULTS Undernourished mice 1083:1109 RESULTS Undernourished mice 1083:1109 RESULTS Undernourished mice completely recovered deficits of 36% weight and 9% length by 3 wk of refeeding, at which time they had 1.4-fold higher plasma phenyllactate and 2.0-fold higher urinary p-cresol sulfate concentrations than did controls. 27052538 12 100 from wk 1976:1977 arg1 microbiota 1935:1944 microbiota 1935:1944 microbiota from undernourished mice at 0 wk 1935:1977 Whereas microbiota from undernourished mice at 0 wk contained 11% less community diversity (P = 0.015), refed mice at 3 wk harbored 1.2-fold greater diversity (P = 0.0006) than did controls. 27052538 9 101 theme plasma 1477:1482 arg1 metabolites 1484:1494 Whereas most urine and plasma metabolites 1454:1494 Whereas most urine and plasma metabolites 1454:1494 Whereas most urine and plasma metabolites normalized with refeeding, 117 fecal metabolites remained altered at 3 wk, including multiple N-linked glycans. 27052538 6 102 theme mass 985:988 arg1 spectrometry 990:1001 mass spectrometry 985:1001 mass spectrometry 985:1001 At 3 time points (0, 1, and 3 wk after ending feed deprivation), metabolites in urine, plasma, and stool were identified with the use of mass spectrometry, and fecal microbes were identified with the use of 16S metagenomic sequencing. 27052538 3 103 theme undernourished 466:479 arg1 mice 490:493 undernourished neonatal mice 466:493 undernourished neonatal mice 466:493 OBJECTIVE We sought to determine whether abnormal metabolomic and intestinal microbiota profiles from undernourished neonatal mice remain altered during catch-up growth. 27052538 10 104 theme proportions 1757:1767 arg1 proportions 1693:1703 lower mean proportions 1682:1703 lower mean proportions of Bacteroidetes (67% compared with 83%) and higher proportions of Firmicutes (26% compared with 16%) 1682:1805 Microbiota profiles from undernourished mice also remained distinct, with lower mean proportions of Bacteroidetes (67% compared with 83%) and higher proportions of Firmicutes (26% compared with 16%). 27052538 0 105 theme Intestinal 49:58 arg1 Microbiota 60:69 an Altered Intestinal Microbiota 38:69 an Altered Intestinal Microbiota 38:69 Microbial-Derived Metabolites Reflect an Altered Intestinal Microbiota during Catch-Up Growth in Undernourished Neonatal Mice. 27052538 13 106 theme neonatal 2241:2248 arg1 mice 2250:2253 undernourished neonatal mice 2226:2253 undernourished neonatal mice 2226:2253 CONCLUSION Microbial-derived metabolites and intestinal microbiota remain altered during catch-up growth in undernourished neonatal mice. 27052538 6 107 theme fecal 1008:1012 arg1 microbes 1014:1021 fecal microbes 1008:1021 fecal microbes 1008:1021 At 3 time points (0, 1, and 3 wk after ending feed deprivation), metabolites in urine, plasma, and stool were identified with the use of mass spectrometry, and fecal microbes were identified with the use of 16S metagenomic sequencing. 27052538 6 108 theme 16S 1055:1057 arg1 sequencing 1071:1080 16S metagenomic sequencing 1055:1080 16S metagenomic sequencing 1055:1080 At 3 time points (0, 1, and 3 wk after ending feed deprivation), metabolites in urine, plasma, and stool were identified with the use of mass spectrometry, and fecal microbes were identified with the use of 16S metagenomic sequencing. 27052538 4 109 theme mouse 562:566 arg1 pups 568:571 Male and female CD1 mouse pups 542:571 Male and female CD1 mouse pups 542:571 METHODS Male and female CD1 mouse pups were undernourished by timed separation from lactating dams for 4 h at 5 d of age, 8 h at 6 d of age, and 12 h/d from 7 to 15 d of age, then resumed ad libitum nursing, whereas controls fed uninterrupted. 27052538 12 110 dep did 2104:2106 arg1 than 2099:2102 than 2099:2102 than 2099:2102 Whereas microbiota from undernourished mice at 0 wk contained 11% less community diversity (P = 0.015), refed mice at 3 wk harbored 1.2-fold greater diversity (P = 0.0006) than did controls. 27052538 13 111 theme catch-up 2207:2214 arg1 growth 2216:2221 catch-up growth 2207:2221 catch-up growth in undernourished neonatal mice 2207:2253 CONCLUSION Microbial-derived metabolites and intestinal microbiota remain altered during catch-up growth in undernourished neonatal mice. 27052538 11 112 theme organisms 1836:1844 arg1 Abundances 1808:1817 Abundances 1808:1817 Abundances of the mucolytic organisms Akkermansia muciniphila and Mucispirillum schaedleri 1808:1897 Abundances of the mucolytic organisms Akkermansia muciniphila and Mucispirillum schaedleri were altered at 0 and 1 wk. 27052538 10 113 theme Firmicutes 1772:1781 arg1 Bacteroidetes 1708:1720 Bacteroidetes 1708:1720 Bacteroidetes (67% compared with 83%) 1708:1744 Microbiota profiles from undernourished mice also remained distinct, with lower mean proportions of Bacteroidetes (67% compared with 83%) and higher proportions of Firmicutes (26% compared with 16%). 27052538 10 113 theme Firmicutes 1772:1781 arg1 proportions 1757:1767 higher proportions 1750:1767 higher proportions of Firmicutes (26% compared with 16%) 1750:1805 Microbiota profiles from undernourished mice also remained distinct, with lower mean proportions of Bacteroidetes (67% compared with 83%) and higher proportions of Firmicutes (26% compared with 16%). 27052538 8 114 theme serotonin 1337:1345 arg1 concentrations 1347:1360 Plasma serotonin concentrations 1330:1360 Plasma serotonin concentrations in undernourished mice 1330:1383 Plasma serotonin concentrations in undernourished mice were 25% lower at 0 wk but 1.5-fold higher than in controls at 3 wk. 27052538 4 115 dep METHODS 534:540 arg1 undernourished 578:591 undernourished 578:591 undernourished 578:591 METHODS Male and female CD1 mouse pups were undernourished by timed separation from lactating dams for 4 h at 5 d of age, 8 h at 6 d of age, and 12 h/d from 7 to 15 d of age, then resumed ad libitum nursing, whereas controls fed uninterrupted. 27052538 7 116 theme % 1160:1160 arg1 length 1162:1167 9% length 1159:1167 9% length 1159:1167 RESULTS Undernourished mice completely recovered deficits of 36% weight and 9% length by 3 wk of refeeding, at which time they had 1.4-fold higher plasma phenyllactate and 2.0-fold higher urinary p-cresol sulfate concentrations than did controls. 27331873 9 0 theme novel 1331:1335 arg1 factor 1346:1351 a novel cellular factor 1329:1351 a novel cellular factor involved in E6 and E7 expressions and cervical cancer tumorigenesis 1329:1419 These findings identify OGT as a novel cellular factor involved in E6 and E7 expressions and cervical cancer tumorigenesis, suggesting that targeting OGT in cervical cancer may have potential therapeutic benefit. 27331873 9 0 theme novel 1331:1335 arg1 OGT 1322:1324 OGT 1322:1324 OGT 1322:1324 These findings identify OGT as a novel cellular factor involved in E6 and E7 expressions and cervical cancer tumorigenesis, suggesting that targeting OGT in cervical cancer may have potential therapeutic benefit. 27331873 6 1 theme cancer 1048:1053 arg1 cells 1055:1059 cervical cancer cells 1039:1059 cervical cancer cells 1039:1059 Moreover, OGT depletion reduced proliferation, invasion, and metastasis in cervical cancer cells. 27331873 9 2 theme cervical 1391:1398 arg1 cancer 1400:1405 cervical cancer 1391:1405 cervical cancer 1391:1405 These findings identify OGT as a novel cellular factor involved in E6 and E7 expressions and cervical cancer tumorigenesis, suggesting that targeting OGT in cervical cancer may have potential therapeutic benefit. 27331873 0 3 theme E6 111:112 arg1 oncogenes 121:129 E6 and E7 oncogenes 111:129 oncogenes 121:129 O-linked N-acetylglucosamine transferase promotes cervical cancer tumorigenesis through human papillomaviruses E6 and E7 oncogenes. 27331873 7 4 from levels 1154:1159 arg1 cells 1193:1197 cervical cancer cells 1177:1197 cervical cancer cells 1177:1197 Further, high glucose enhanced the interaction between OGT and HCF-1, paralleling increased levels of E6 and E7 in cervical cancer cells. 27331873 3 5 theme E7 500:501 arg1 expressions 503:513 HPV E6 and E7 expressions 489:513 HPV E6 and E7 expressions 489:513 Here, we tested whether O-GlcNAc modification of HCF-1 affects HPV E6 and E7 expressions and tumorigenesis of cervical cancer. 27331873 4 6 theme depleting 567:575 arg1 OGT 577:579 depleting OGT 567:579 depleting OGT with OGT-specific shRNA 567:603 We found that depleting OGT with OGT-specific shRNA significantly decreased levels of E6 and E7 oncoproteins, and cervical cancer tumorigenesis, while OGT overexpression greatly increased levels of E6 and E7 oncoproteins. 27331873 3 7 theme cervical 536:543 arg1 cancer 545:550 cervical cancer 536:550 cervical cancer 536:550 Here, we tested whether O-GlcNAc modification of HCF-1 affects HPV E6 and E7 expressions and tumorigenesis of cervical cancer. 27331873 4 8 theme E6 751:752 arg1 levels 741:746 levels 741:746 levels of E6 and E7 oncoproteins 741:772 We found that depleting OGT with OGT-specific shRNA significantly decreased levels of E6 and E7 oncoproteins, and cervical cancer tumorigenesis, while OGT overexpression greatly increased levels of E6 and E7 oncoproteins. 27331873 4 9 theme OGT-specific 586:597 arg1 shRNA 599:603 OGT-specific shRNA 586:603 OGT-specific shRNA 586:603 We found that depleting OGT with OGT-specific shRNA significantly decreased levels of E6 and E7 oncoproteins, and cervical cancer tumorigenesis, while OGT overexpression greatly increased levels of E6 and E7 oncoproteins. 27331873 0 10 theme E7 118:119 arg1 oncogenes 121:129 E6 and E7 oncogenes 111:129 oncogenes 121:129 O-linked N-acetylglucosamine transferase promotes cervical cancer tumorigenesis through human papillomaviruses E6 and E7 oncogenes. 27331873 9 11 theme potential 1480:1488 arg1 benefit 1502:1508 potential therapeutic benefit 1480:1508 potential therapeutic benefit 1480:1508 These findings identify OGT as a novel cellular factor involved in E6 and E7 expressions and cervical cancer tumorigenesis, suggesting that targeting OGT in cervical cancer may have potential therapeutic benefit. 27331873 4 12 theme E7 758:759 arg1 levels 741:746 levels 741:746 levels of E6 and E7 oncoproteins 741:772 We found that depleting OGT with OGT-specific shRNA significantly decreased levels of E6 and E7 oncoproteins, and cervical cancer tumorigenesis, while OGT overexpression greatly increased levels of E6 and E7 oncoproteins. 27331873 3 13 theme cancer 545:550 arg1 tumorigenesis 519:531 tumorigenesis 519:531 tumorigenesis 519:531 Here, we tested whether O-GlcNAc modification of HCF-1 affects HPV E6 and E7 expressions and tumorigenesis of cervical cancer. 27331873 3 13 theme cancer 545:550 arg1 expressions 503:513 HPV E6 and E7 expressions 489:513 HPV E6 and E7 expressions 489:513 Here, we tested whether O-GlcNAc modification of HCF-1 affects HPV E6 and E7 expressions and tumorigenesis of cervical cancer. 27331873 9 14 theme targeting 1438:1446 arg1 OGT 1448:1450 targeting OGT 1438:1450 targeting OGT in cervical cancer 1438:1469 These findings identify OGT as a novel cellular factor involved in E6 and E7 expressions and cervical cancer tumorigenesis, suggesting that targeting OGT in cervical cancer may have potential therapeutic benefit. 27331873 3 15 mod modification 459:470 arg1 HCF-1 475:479 HCF-1 475:479 HCF-1 475:479 Here, we tested whether O-GlcNAc modification of HCF-1 affects HPV E6 and E7 expressions and tumorigenesis of cervical cancer. 27331873 3 15 mod modification 459:470 arg3 O-GlcNAc 450:457 O-GlcNAc modification 450:470 O-GlcNAc modification of HCF-1 450:479 Here, we tested whether O-GlcNAc modification of HCF-1 affects HPV E6 and E7 expressions and tumorigenesis of cervical cancer. 27331873 7 16 theme cervical 1177:1184 arg1 cells 1193:1197 cervical cancer cells 1177:1197 cervical cancer cells 1177:1197 Further, high glucose enhanced the interaction between OGT and HCF-1, paralleling increased levels of E6 and E7 in cervical cancer cells. 27331873 3 17 theme HPV 489:491 arg1 E6 493:494 HPV E6 489:494 HPV E6 489:494 Here, we tested whether O-GlcNAc modification of HCF-1 affects HPV E6 and E7 expressions and tumorigenesis of cervical cancer. 27331873 6 18 from proliferation 996:1008 arg1 cells 1055:1059 cervical cancer cells 1039:1059 cervical cancer cells 1039:1059 Moreover, OGT depletion reduced proliferation, invasion, and metastasis in cervical cancer cells. 27331873 0 19 link O-linked 0:7 arg1 transferase 29:39 O-linked N-acetylglucosamine transferase 0:39 O-linked N-acetylglucosamine transferase 0:39 O-linked N-acetylglucosamine transferase promotes cervical cancer tumorigenesis through human papillomaviruses E6 and E7 oncogenes. 27331873 8 20 theme HeLa 1248:1251 arg1 cells 1253:1257 HeLa cells 1248:1257 HeLa cells 1248:1257 Most importantly, we found that reducing OGT in HeLa cells caused decreased tumor growth in vivo. 27331873 4 21 dep E6 751:752 arg1 oncoproteins 761:772 oncoproteins 761:772 oncoproteins 761:772 We found that depleting OGT with OGT-specific shRNA significantly decreased levels of E6 and E7 oncoproteins, and cervical cancer tumorigenesis, while OGT overexpression greatly increased levels of E6 and E7 oncoproteins. 27331873 5 22 theme dose-dependent 810:823 arg1 increases 825:833 dose-dependent increases 810:833 dose-dependent increases in the transcriptional activity of E6 and E7 810:878 Notably, OGT overexpression caused dose-dependent increases in the transcriptional activity of E6 and E7, and this activity was decreased when HCF-1 was depleted with HCF-1-specific siRNA. 27331873 1 23 theme O-GlcNAc 200:207 arg1 modification 209:220 O-GlcNAc modification 200:220 O-GlcNAc modification (O-GlcNAcylation) 200:238 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) increases O-GlcNAc modification (O-GlcNAcylation), and transcriptional co-regulator host cell factor 1 (HCF-1) is one of OGT targets. 27331873 1 23 theme O-GlcNAc 200:207 arg1 O-GlcNAcylation 223:237 O-GlcNAcylation 223:237 O-GlcNAcylation 223:237 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) increases O-GlcNAc modification (O-GlcNAcylation), and transcriptional co-regulator host cell factor 1 (HCF-1) is one of OGT targets. 27331873 0 24 theme N-acetylglucosamine 9:27 arg1 transferase 29:39 O-linked N-acetylglucosamine transferase 0:39 O-linked N-acetylglucosamine transferase 0:39 O-linked N-acetylglucosamine transferase promotes cervical cancer tumorigenesis through human papillomaviruses E6 and E7 oncogenes. 27331873 5 25 from increases 825:833 arg1 activity 858:865 the transcriptional activity 838:865 the transcriptional activity of E6 and E7 838:878 Notably, OGT overexpression caused dose-dependent increases in the transcriptional activity of E6 and E7, and this activity was decreased when HCF-1 was depleted with HCF-1-specific siRNA. 27331873 6 26 from invasion 1011:1018 arg1 cells 1055:1059 cervical cancer cells 1039:1059 cervical cancer cells 1039:1059 Moreover, OGT depletion reduced proliferation, invasion, and metastasis in cervical cancer cells. 27331873 2 27 theme High-risk 324:332 arg1 HPVs 358:361 HPVs 358:361 HPVs 358:361 High-risk Human Papillomaviruses (HPVs) encode E6 and E7 oncoproteins, which promote cervical cancer. 27331873 2 27 theme High-risk 324:332 arg1 Papillomaviruses 340:355 High-risk Human Papillomaviruses 324:355 High-risk Human Papillomaviruses (HPVs) 324:362 High-risk Human Papillomaviruses (HPVs) encode E6 and E7 oncoproteins, which promote cervical cancer. 27331873 2 27 theme High-risk 324:332 arg1 oncoproteins 381:392 E6 and E7 oncoproteins 371:392 E6 and E7 oncoproteins 371:392 High-risk Human Papillomaviruses (HPVs) encode E6 and E7 oncoproteins, which promote cervical cancer. 27331873 7 28 theme E7 1171:1172 arg1 levels 1154:1159 increased levels 1144:1159 increased levels of E6 and E7 in cervical cancer cells 1144:1197 Further, high glucose enhanced the interaction between OGT and HCF-1, paralleling increased levels of E6 and E7 in cervical cancer cells. 27331873 4 29 theme cervical 667:674 arg1 tumorigenesis 683:695 cervical cancer tumorigenesis 667:695 cervical cancer tumorigenesis 667:695 We found that depleting OGT with OGT-specific shRNA significantly decreased levels of E6 and E7 oncoproteins, and cervical cancer tumorigenesis, while OGT overexpression greatly increased levels of E6 and E7 oncoproteins. 27331873 0 30 theme O-linked 0:7 arg1 transferase 29:39 O-linked N-acetylglucosamine transferase 0:39 O-linked N-acetylglucosamine transferase 0:39 O-linked N-acetylglucosamine transferase promotes cervical cancer tumorigenesis through human papillomaviruses E6 and E7 oncogenes. 27331873 5 31 theme E7 877:878 arg1 activity 858:865 the transcriptional activity 838:865 the transcriptional activity of E6 and E7 838:878 Notably, OGT overexpression caused dose-dependent increases in the transcriptional activity of E6 and E7, and this activity was decreased when HCF-1 was depleted with HCF-1-specific siRNA. 27331873 2 32 theme E7 378:379 arg1 oncoproteins 381:392 E6 and E7 oncoproteins 371:392 E6 and E7 oncoproteins 371:392 High-risk Human Papillomaviruses (HPVs) encode E6 and E7 oncoproteins, which promote cervical cancer. 27331873 2 32 theme E7 378:379 arg1 Papillomaviruses 340:355 High-risk Human Papillomaviruses 324:355 High-risk Human Papillomaviruses (HPVs) 324:362 High-risk Human Papillomaviruses (HPVs) encode E6 and E7 oncoproteins, which promote cervical cancer. 27331873 7 33 theme E6 1164:1165 arg1 levels 1154:1159 increased levels 1144:1159 increased levels of E6 and E7 in cervical cancer cells 1144:1197 Further, high glucose enhanced the interaction between OGT and HCF-1, paralleling increased levels of E6 and E7 in cervical cancer cells. 27331873 6 34 theme OGT 974:976 arg1 depletion 978:986 OGT depletion 974:986 OGT depletion 974:986 Moreover, OGT depletion reduced proliferation, invasion, and metastasis in cervical cancer cells. 27331873 7 35 theme high 1071:1074 arg1 glucose 1076:1082 high glucose 1071:1082 high glucose 1071:1082 Further, high glucose enhanced the interaction between OGT and HCF-1, paralleling increased levels of E6 and E7 in cervical cancer cells. 27331873 0 36 dep papillomaviruses 94:109 arg1 oncogenes 121:129 E6 and E7 oncogenes 111:129 oncogenes 121:129 O-linked N-acetylglucosamine transferase promotes cervical cancer tumorigenesis through human papillomaviruses E6 and E7 oncogenes. 27331873 4 37 theme E6 639:640 arg1 levels 629:634 levels 629:634 levels of E6 and E7 oncoproteins, and cervical cancer tumorigenesis 629:695 We found that depleting OGT with OGT-specific shRNA significantly decreased levels of E6 and E7 oncoproteins, and cervical cancer tumorigenesis, while OGT overexpression greatly increased levels of E6 and E7 oncoproteins. 27331873 5 38 theme HCF-1-specific 942:955 arg1 siRNA 957:961 HCF-1-specific siRNA 942:961 HCF-1-specific siRNA 942:961 Notably, OGT overexpression caused dose-dependent increases in the transcriptional activity of E6 and E7, and this activity was decreased when HCF-1 was depleted with HCF-1-specific siRNA. 27331873 9 39 contain have 1475:1478 arg1 OGT 1448:1450 targeting OGT 1438:1450 targeting OGT in cervical cancer 1438:1469 These findings identify OGT as a novel cellular factor involved in E6 and E7 expressions and cervical cancer tumorigenesis, suggesting that targeting OGT in cervical cancer may have potential therapeutic benefit. 27331873 9 39 contain have 1475:1478 arg2 benefit 1502:1508 potential therapeutic benefit 1480:1508 potential therapeutic benefit 1480:1508 These findings identify OGT as a novel cellular factor involved in E6 and E7 expressions and cervical cancer tumorigenesis, suggesting that targeting OGT in cervical cancer may have potential therapeutic benefit. 27331873 1 40 theme O-linked 132:139 arg1 O-GlcNAc 162:169 O-GlcNAc 162:169 O-GlcNAc 162:169 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) increases O-GlcNAc modification (O-GlcNAcylation), and transcriptional co-regulator host cell factor 1 (HCF-1) is one of OGT targets. 27331873 1 40 theme O-linked 132:139 arg1 N-acetylglucosamine 141:159 O-linked N-acetylglucosamine 132:159 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) 132:188 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) increases O-GlcNAc modification (O-GlcNAcylation), and transcriptional co-regulator host cell factor 1 (HCF-1) is one of OGT targets. 27331873 9 41 theme therapeutic 1490:1500 arg1 benefit 1502:1508 potential therapeutic benefit 1480:1508 potential therapeutic benefit 1480:1508 These findings identify OGT as a novel cellular factor involved in E6 and E7 expressions and cervical cancer tumorigenesis, suggesting that targeting OGT in cervical cancer may have potential therapeutic benefit. 27331873 0 42 theme cancer 59:64 arg1 tumorigenesis 66:78 cervical cancer tumorigenesis 50:78 cervical cancer tumorigenesis 50:78 O-linked N-acetylglucosamine transferase promotes cervical cancer tumorigenesis through human papillomaviruses E6 and E7 oncogenes. 27331873 4 43 theme OGT 704:706 arg1 overexpression 708:721 OGT overexpression 704:721 OGT overexpression 704:721 We found that depleting OGT with OGT-specific shRNA significantly decreased levels of E6 and E7 oncoproteins, and cervical cancer tumorigenesis, while OGT overexpression greatly increased levels of E6 and E7 oncoproteins. 27331873 4 44 theme E7 646:647 arg1 oncoproteins 649:660 E7 oncoproteins 646:660 E7 oncoproteins 646:660 We found that depleting OGT with OGT-specific shRNA significantly decreased levels of E6 and E7 oncoproteins, and cervical cancer tumorigenesis, while OGT overexpression greatly increased levels of E6 and E7 oncoproteins. 27331873 8 45 theme reducing 1232:1239 arg1 OGT 1241:1243 reducing OGT 1232:1243 reducing OGT in HeLa cells 1232:1257 Most importantly, we found that reducing OGT in HeLa cells caused decreased tumor growth in vivo. 27331873 2 46 theme cervical 409:416 arg1 cancer 418:423 cervical cancer 409:423 cervical cancer 409:423 High-risk Human Papillomaviruses (HPVs) encode E6 and E7 oncoproteins, which promote cervical cancer. 27331873 0 47 theme cervical 50:57 arg1 tumorigenesis 66:78 cervical cancer tumorigenesis 50:78 cervical cancer tumorigenesis 50:78 O-linked N-acetylglucosamine transferase promotes cervical cancer tumorigenesis through human papillomaviruses E6 and E7 oncogenes. 27331873 1 48 theme OGT 311:313 arg1 targets 315:321 OGT targets 311:321 OGT targets 311:321 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) increases O-GlcNAc modification (O-GlcNAcylation), and transcriptional co-regulator host cell factor 1 (HCF-1) is one of OGT targets. 27331873 5 49 theme OGT 784:786 arg1 overexpression 788:801 OGT overexpression 784:801 OGT overexpression 784:801 Notably, OGT overexpression caused dose-dependent increases in the transcriptional activity of E6 and E7, and this activity was decreased when HCF-1 was depleted with HCF-1-specific siRNA. 27331873 8 50 from OGT 1241:1243 arg1 cells 1253:1257 HeLa cells 1248:1257 HeLa cells 1248:1257 Most importantly, we found that reducing OGT in HeLa cells caused decreased tumor growth in vivo. 27331873 3 51 theme O-GlcNAc 450:457 arg1 modification 459:470 O-GlcNAc modification 450:470 O-GlcNAc modification of HCF-1 450:479 Here, we tested whether O-GlcNAc modification of HCF-1 affects HPV E6 and E7 expressions and tumorigenesis of cervical cancer. 27331873 8 52 theme tumor 1276:1280 arg1 growth 1282:1287 decreased tumor growth 1266:1287 decreased tumor growth 1266:1287 Most importantly, we found that reducing OGT in HeLa cells caused decreased tumor growth in vivo. 27331873 1 53 theme targets 315:321 arg1 one 304:306 one 304:306 one 304:306 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) increases O-GlcNAc modification (O-GlcNAcylation), and transcriptional co-regulator host cell factor 1 (HCF-1) is one of OGT targets. 27331873 1 53 theme targets 315:321 arg1 targets 315:321 OGT targets 311:321 OGT targets 311:321 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) increases O-GlcNAc modification (O-GlcNAcylation), and transcriptional co-regulator host cell factor 1 (HCF-1) is one of OGT targets. 27331873 6 54 theme cervical 1039:1046 arg1 cells 1055:1059 cervical cancer cells 1039:1059 cervical cancer cells 1039:1059 Moreover, OGT depletion reduced proliferation, invasion, and metastasis in cervical cancer cells. 27331873 0 55 theme human 88:92 arg1 papillomaviruses 94:109 human papillomaviruses E6 and E7 oncogenes 88:129 human papillomaviruses E6 and E7 oncogenes 88:129 O-linked N-acetylglucosamine transferase promotes cervical cancer tumorigenesis through human papillomaviruses E6 and E7 oncogenes. 27331873 9 56 dep E6 1365:1366 arg1 tumorigenesis 1407:1419 tumorigenesis 1407:1419 tumorigenesis 1407:1419 These findings identify OGT as a novel cellular factor involved in E6 and E7 expressions and cervical cancer tumorigenesis, suggesting that targeting OGT in cervical cancer may have potential therapeutic benefit. 27331873 9 56 dep E6 1365:1366 arg1 expressions 1375:1385 expressions 1375:1385 expressions 1375:1385 These findings identify OGT as a novel cellular factor involved in E6 and E7 expressions and cervical cancer tumorigenesis, suggesting that targeting OGT in cervical cancer may have potential therapeutic benefit. 27331873 1 57 theme N-acetylglucosamine 141:159 arg1 OGT 185:187 OGT 185:187 OGT 185:187 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) increases O-GlcNAc modification (O-GlcNAcylation), and transcriptional co-regulator host cell factor 1 (HCF-1) is one of OGT targets. 27331873 1 57 theme N-acetylglucosamine 141:159 arg1 transferase 172:182 O-linked N-acetylglucosamine (O-GlcNAc) transferase 132:182 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) 132:188 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) increases O-GlcNAc modification (O-GlcNAcylation), and transcriptional co-regulator host cell factor 1 (HCF-1) is one of OGT targets. 27331873 7 58 theme increased 1144:1152 arg1 levels 1154:1159 increased levels 1144:1159 increased levels of E6 and E7 in cervical cancer cells 1144:1197 Further, high glucose enhanced the interaction between OGT and HCF-1, paralleling increased levels of E6 and E7 in cervical cancer cells. 27331873 7 59 theme cancer 1186:1191 arg1 cells 1193:1197 cervical cancer cells 1177:1197 cervical cancer cells 1177:1197 Further, high glucose enhanced the interaction between OGT and HCF-1, paralleling increased levels of E6 and E7 in cervical cancer cells. 27331873 3 60 theme E6 493:494 arg1 expressions 503:513 HPV E6 and E7 expressions 489:513 HPV E6 and E7 expressions 489:513 Here, we tested whether O-GlcNAc modification of HCF-1 affects HPV E6 and E7 expressions and tumorigenesis of cervical cancer. 27331873 4 61 theme cancer 676:681 arg1 tumorigenesis 683:695 cervical cancer tumorigenesis 667:695 cervical cancer tumorigenesis 667:695 We found that depleting OGT with OGT-specific shRNA significantly decreased levels of E6 and E7 oncoproteins, and cervical cancer tumorigenesis, while OGT overexpression greatly increased levels of E6 and E7 oncoproteins. 27331873 3 62 theme HCF-1 475:479 arg1 modification 459:470 O-GlcNAc modification 450:470 O-GlcNAc modification of HCF-1 450:479 Here, we tested whether O-GlcNAc modification of HCF-1 affects HPV E6 and E7 expressions and tumorigenesis of cervical cancer. 27331873 1 63 theme transcriptional 245:259 arg1 factor 284:289 transcriptional co-regulator host cell factor 1 245:291 transcriptional co-regulator host cell factor 1 (HCF-1) 245:299 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) increases O-GlcNAc modification (O-GlcNAcylation), and transcriptional co-regulator host cell factor 1 (HCF-1) is one of OGT targets. 27331873 1 63 theme transcriptional 245:259 arg1 HCF-1 294:298 HCF-1 294:298 HCF-1 294:298 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) increases O-GlcNAc modification (O-GlcNAcylation), and transcriptional co-regulator host cell factor 1 (HCF-1) is one of OGT targets. 27331873 9 64 from OGT 1448:1450 arg1 cancer 1464:1469 cervical cancer 1455:1469 cervical cancer 1455:1469 These findings identify OGT as a novel cellular factor involved in E6 and E7 expressions and cervical cancer tumorigenesis, suggesting that targeting OGT in cervical cancer may have potential therapeutic benefit. 27331873 2 65 theme Human 334:338 arg1 HPVs 358:361 HPVs 358:361 HPVs 358:361 High-risk Human Papillomaviruses (HPVs) encode E6 and E7 oncoproteins, which promote cervical cancer. 27331873 2 65 theme Human 334:338 arg1 Papillomaviruses 340:355 High-risk Human Papillomaviruses 324:355 High-risk Human Papillomaviruses (HPVs) 324:362 High-risk Human Papillomaviruses (HPVs) encode E6 and E7 oncoproteins, which promote cervical cancer. 27331873 2 65 theme Human 334:338 arg1 oncoproteins 381:392 E6 and E7 oncoproteins 371:392 E6 and E7 oncoproteins 371:392 High-risk Human Papillomaviruses (HPVs) encode E6 and E7 oncoproteins, which promote cervical cancer. 27331873 1 66 theme co-regulator 261:272 arg1 factor 284:289 transcriptional co-regulator host cell factor 1 245:291 transcriptional co-regulator host cell factor 1 (HCF-1) 245:299 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) increases O-GlcNAc modification (O-GlcNAcylation), and transcriptional co-regulator host cell factor 1 (HCF-1) is one of OGT targets. 27331873 1 66 theme co-regulator 261:272 arg1 HCF-1 294:298 HCF-1 294:298 HCF-1 294:298 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) increases O-GlcNAc modification (O-GlcNAcylation), and transcriptional co-regulator host cell factor 1 (HCF-1) is one of OGT targets. 27331873 9 67 theme cervical 1455:1462 arg1 cancer 1464:1469 cervical cancer 1455:1469 cervical cancer 1455:1469 These findings identify OGT as a novel cellular factor involved in E6 and E7 expressions and cervical cancer tumorigenesis, suggesting that targeting OGT in cervical cancer may have potential therapeutic benefit. 27331873 5 68 theme E6 870:871 arg1 activity 858:865 the transcriptional activity 838:865 the transcriptional activity of E6 and E7 838:878 Notably, OGT overexpression caused dose-dependent increases in the transcriptional activity of E6 and E7, and this activity was decreased when HCF-1 was depleted with HCF-1-specific siRNA. 27331873 4 69 with OGT 577:579 arg1 shRNA 599:603 OGT-specific shRNA 586:603 OGT-specific shRNA 586:603 We found that depleting OGT with OGT-specific shRNA significantly decreased levels of E6 and E7 oncoproteins, and cervical cancer tumorigenesis, while OGT overexpression greatly increased levels of E6 and E7 oncoproteins. 27331873 5 70 theme transcriptional 842:856 arg1 activity 858:865 the transcriptional activity 838:865 the transcriptional activity of E6 and E7 838:878 Notably, OGT overexpression caused dose-dependent increases in the transcriptional activity of E6 and E7, and this activity was decreased when HCF-1 was depleted with HCF-1-specific siRNA. 27331873 4 71 theme tumorigenesis 683:695 arg1 levels 629:634 levels 629:634 levels of E6 and E7 oncoproteins, and cervical cancer tumorigenesis 629:695 We found that depleting OGT with OGT-specific shRNA significantly decreased levels of E6 and E7 oncoproteins, and cervical cancer tumorigenesis, while OGT overexpression greatly increased levels of E6 and E7 oncoproteins. 27331873 4 72 theme oncoproteins 649:660 arg1 levels 629:634 levels 629:634 levels of E6 and E7 oncoproteins, and cervical cancer tumorigenesis 629:695 We found that depleting OGT with OGT-specific shRNA significantly decreased levels of E6 and E7 oncoproteins, and cervical cancer tumorigenesis, while OGT overexpression greatly increased levels of E6 and E7 oncoproteins. 27331873 1 73 theme host 274:277 arg1 factor 284:289 transcriptional co-regulator host cell factor 1 245:291 transcriptional co-regulator host cell factor 1 (HCF-1) 245:299 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) increases O-GlcNAc modification (O-GlcNAcylation), and transcriptional co-regulator host cell factor 1 (HCF-1) is one of OGT targets. 27331873 1 73 theme host 274:277 arg1 HCF-1 294:298 HCF-1 294:298 HCF-1 294:298 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) increases O-GlcNAc modification (O-GlcNAcylation), and transcriptional co-regulator host cell factor 1 (HCF-1) is one of OGT targets. 27331873 1 74 link O-linked 132:139 arg1 O-GlcNAc 162:169 O-GlcNAc 162:169 O-GlcNAc 162:169 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) increases O-GlcNAc modification (O-GlcNAcylation), and transcriptional co-regulator host cell factor 1 (HCF-1) is one of OGT targets. 27331873 1 74 link O-linked 132:139 arg1 N-acetylglucosamine 141:159 O-linked N-acetylglucosamine 132:159 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) 132:188 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) increases O-GlcNAc modification (O-GlcNAcylation), and transcriptional co-regulator host cell factor 1 (HCF-1) is one of OGT targets. 27331873 9 75 theme cellular 1337:1344 arg1 factor 1346:1351 a novel cellular factor 1329:1351 a novel cellular factor involved in E6 and E7 expressions and cervical cancer tumorigenesis 1329:1419 These findings identify OGT as a novel cellular factor involved in E6 and E7 expressions and cervical cancer tumorigenesis, suggesting that targeting OGT in cervical cancer may have potential therapeutic benefit. 27331873 9 75 theme cellular 1337:1344 arg1 OGT 1322:1324 OGT 1322:1324 OGT 1322:1324 These findings identify OGT as a novel cellular factor involved in E6 and E7 expressions and cervical cancer tumorigenesis, suggesting that targeting OGT in cervical cancer may have potential therapeutic benefit. 27331873 6 76 from metastasis 1025:1034 arg1 cells 1055:1059 cervical cancer cells 1039:1059 cervical cancer cells 1039:1059 Moreover, OGT depletion reduced proliferation, invasion, and metastasis in cervical cancer cells. 27331873 2 77 theme E6 371:372 arg1 oncoproteins 381:392 E6 and E7 oncoproteins 371:392 E6 and E7 oncoproteins 371:392 High-risk Human Papillomaviruses (HPVs) encode E6 and E7 oncoproteins, which promote cervical cancer. 27331873 2 77 theme E6 371:372 arg1 Papillomaviruses 340:355 High-risk Human Papillomaviruses 324:355 High-risk Human Papillomaviruses (HPVs) 324:362 High-risk Human Papillomaviruses (HPVs) encode E6 and E7 oncoproteins, which promote cervical cancer. 27331873 8 78 theme decreased 1266:1274 arg1 growth 1282:1287 decreased tumor growth 1266:1287 decreased tumor growth 1266:1287 Most importantly, we found that reducing OGT in HeLa cells caused decreased tumor growth in vivo. 27331873 1 79 theme cell 279:282 arg1 factor 284:289 transcriptional co-regulator host cell factor 1 245:291 transcriptional co-regulator host cell factor 1 (HCF-1) 245:299 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) increases O-GlcNAc modification (O-GlcNAcylation), and transcriptional co-regulator host cell factor 1 (HCF-1) is one of OGT targets. 27331873 1 79 theme cell 279:282 arg1 HCF-1 294:298 HCF-1 294:298 HCF-1 294:298 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) increases O-GlcNAc modification (O-GlcNAcylation), and transcriptional co-regulator host cell factor 1 (HCF-1) is one of OGT targets. 26526581 4 0 theme N-glycans 505:513 arg1 expression 470:479 the expression 466:479 the expression of β1,6-GlcNAc branched N-glycans in nonneoplastic brain and glioma samples 466:555 In this study, the expression of β1,6-GlcNAc branched N-glycans in nonneoplastic brain and glioma samples was characterized by lectin histochemistry. 26526581 4 1 theme β1,6-GlcNAc 484:494 arg1 N-glycans 505:513 β1,6-GlcNAc branched N-glycans 484:513 β1,6-GlcNAc branched N-glycans 484:513 In this study, the expression of β1,6-GlcNAc branched N-glycans in nonneoplastic brain and glioma samples was characterized by lectin histochemistry. 26526581 5 2 theme glioma 625:630 arg1 cells 632:636 glioma cells 625:636 glioma cells 625:636 The radiosensitivity of glioma cells was evaluated by colony formation assay. 26526581 9 3 from increase 1161:1168 arg1 number 1177:1182 the number 1173:1182 the number of apoptotic cells 1173:1201 Meanwhile, the G2/M checkpoint was impaired and there was an increase in the number of apoptotic cells. 26526581 4 4 theme nonneoplastic 518:530 arg1 brain 532:536 nonneoplastic brain and glioma samples 518:555 brain 532:536 In this study, the expression of β1,6-GlcNAc branched N-glycans in nonneoplastic brain and glioma samples was characterized by lectin histochemistry. 26526581 5 5 theme cells 632:636 arg1 radiosensitivity 605:620 The radiosensitivity 601:620 The radiosensitivity of glioma cells 601:636 The radiosensitivity of glioma cells was evaluated by colony formation assay. 26526581 10 6 theme cells 1310:1314 arg1 radiosensitivity 1285:1300 the radiosensitivity 1281:1300 the radiosensitivity of U251 cells 1281:1314 Tunicamycin, an inhibitor of N-glycan biosynthesis, was also able to enhance the radiosensitivity of U251 cells. 26526581 3 7 theme β1,6-GlcNAc 364:374 arg1 expression 385:394 β1,6-GlcNAc branched expression 364:394 β1,6-GlcNAc branched expression 364:394 However, the relationship between β1,6-GlcNAc branched expression and radiosensitivity in glioma cells is still unknown. 26526581 8 8 theme branches 995:1002 arg1 inhibition 960:969 the inhibition 956:969 the inhibition of N-linked β1,6-GlcNAc branches by GnT-V silencing in U251 cells 956:1035 Furthermore, the inhibition of N-linked β1,6-GlcNAc branches by GnT-V silencing in U251 cells could reduce the cell clonogenic survival after X-irradiation. 26526581 8 9 theme clonogenic 1059:1068 arg1 survival 1070:1077 the cell clonogenic survival 1050:1077 the cell clonogenic survival 1050:1077 Furthermore, the inhibition of N-linked β1,6-GlcNAc branches by GnT-V silencing in U251 cells could reduce the cell clonogenic survival after X-irradiation. 26526581 7 10 theme glioblastoma 923:934 arg1 cells 936:940 glioblastoma cells 923:940 glioblastoma cells 923:940 In addition, β1,6-GlcNAc branched expression was negatively correlated with the radiosensitivity of glioblastoma cells. 26526581 3 11 from expression 385:394 arg1 cells 427:431 glioma cells 420:431 glioma cells 420:431 However, the relationship between β1,6-GlcNAc branched expression and radiosensitivity in glioma cells is still unknown. 26526581 11 12 theme therapeutic 1363:1373 arg1 approaches 1375:1384 therapeutic approaches 1363:1384 therapeutic approaches targeting N-linked β1,6-GlcNAc branches 1363:1424 Thus, our results suggest that development of therapeutic approaches targeting N-linked β1,6-GlcNAc branches may be a promising strategy in glioblastoma treatment. 26526581 8 13 theme cell 1054:1057 arg1 survival 1070:1077 the cell clonogenic survival 1050:1077 the cell clonogenic survival 1050:1077 Furthermore, the inhibition of N-linked β1,6-GlcNAc branches by GnT-V silencing in U251 cells could reduce the cell clonogenic survival after X-irradiation. 26526581 6 14 theme glioblastoma 739:750 arg1 specimens 752:760 glioblastoma specimens 739:760 glioblastoma specimens 739:760 We found that β1,6-GlcNAc branches were highly expressed in glioblastoma specimens, compared with diffuse astrocytomas and nonneoplastic brain. 26526581 8 15 from silencing 1013:1021 arg1 cells 1031:1035 U251 cells 1026:1035 U251 cells 1026:1035 Furthermore, the inhibition of N-linked β1,6-GlcNAc branches by GnT-V silencing in U251 cells could reduce the cell clonogenic survival after X-irradiation. 26526581 4 16 theme branched 496:503 arg1 N-glycans 505:513 β1,6-GlcNAc branched N-glycans 484:513 β1,6-GlcNAc branched N-glycans 484:513 In this study, the expression of β1,6-GlcNAc branched N-glycans in nonneoplastic brain and glioma samples was characterized by lectin histochemistry. 26526581 5 17 theme colony 655:660 arg1 assay 672:676 colony formation assay 655:676 colony formation assay 655:676 The radiosensitivity of glioma cells was evaluated by colony formation assay. 26526581 8 18 theme N-linked 974:981 arg1 branches 995:1002 N-linked β1,6-GlcNAc branches 974:1002 N-linked β1,6-GlcNAc branches 974:1002 Furthermore, the inhibition of N-linked β1,6-GlcNAc branches by GnT-V silencing in U251 cells could reduce the cell clonogenic survival after X-irradiation. 26526581 11 19 theme β1,6-GlcNAc 1405:1415 arg1 branches 1417:1424 N-linked β1,6-GlcNAc branches 1396:1424 N-linked β1,6-GlcNAc branches 1396:1424 Thus, our results suggest that development of therapeutic approaches targeting N-linked β1,6-GlcNAc branches may be a promising strategy in glioblastoma treatment. 26526581 3 20 from radiosensitivity 400:415 arg1 cells 427:431 glioma cells 420:431 glioma cells 420:431 However, the relationship between β1,6-GlcNAc branched expression and radiosensitivity in glioma cells is still unknown. 26526581 5 21 theme formation 662:670 arg1 assay 672:676 colony formation assay 655:676 colony formation assay 655:676 The radiosensitivity of glioma cells was evaluated by colony formation assay. 26526581 2 22 theme glioma 310:315 arg1 progression 317:327 glioma progression 310:327 glioma progression 310:327 β1,6-GlcNAc branched N-glycans, which are encoded by N-acetylglucosaminyltransferase V (GnT-V), play important roles in glioma progression. 26526581 1 23 theme radiation 171:179 arg1 therapy 181:187 radiation therapy 171:187 radiation therapy 171:187 Gliomas are the most prevalent type of primary brain tumors and are resistant to radiation therapy. 26526581 8 24 theme U251 1026:1029 arg1 cells 1031:1035 U251 cells 1026:1035 U251 cells 1026:1035 Furthermore, the inhibition of N-linked β1,6-GlcNAc branches by GnT-V silencing in U251 cells could reduce the cell clonogenic survival after X-irradiation. 26526581 4 25 from expression 470:479 arg1 samples 549:555 nonneoplastic brain and glioma samples 518:555 samples 549:555 In this study, the expression of β1,6-GlcNAc branched N-glycans in nonneoplastic brain and glioma samples was characterized by lectin histochemistry. 26526581 4 25 from expression 470:479 arg1 brain 532:536 nonneoplastic brain and glioma samples 518:555 brain 532:536 In this study, the expression of β1,6-GlcNAc branched N-glycans in nonneoplastic brain and glioma samples was characterized by lectin histochemistry. 26526581 3 26 theme branched 376:383 arg1 expression 385:394 β1,6-GlcNAc branched expression 364:394 β1,6-GlcNAc branched expression 364:394 However, the relationship between β1,6-GlcNAc branched expression and radiosensitivity in glioma cells is still unknown. 26526581 0 27 theme human 22:26 arg1 cells 35:39 human glioma cells 22:39 human glioma cells 22:39 Radiosensitisation of human glioma cells by inhibition of β1,6-GlcNAc branched N-glycans. 26526581 7 28 theme β1,6-GlcNAc 836:846 arg1 expression 857:866 β1,6-GlcNAc branched expression 836:866 β1,6-GlcNAc branched expression 836:866 In addition, β1,6-GlcNAc branched expression was negatively correlated with the radiosensitivity of glioblastoma cells. 26526581 2 29 theme important 291:299 arg1 roles 301:305 important roles 291:305 important roles 291:305 β1,6-GlcNAc branched N-glycans, which are encoded by N-acetylglucosaminyltransferase V (GnT-V), play important roles in glioma progression. 26526581 8 30 theme β1,6-GlcNAc 983:993 arg1 branches 995:1002 N-linked β1,6-GlcNAc branches 974:1002 N-linked β1,6-GlcNAc branches 974:1002 Furthermore, the inhibition of N-linked β1,6-GlcNAc branches by GnT-V silencing in U251 cells could reduce the cell clonogenic survival after X-irradiation. 26526581 4 31 theme lectin 578:583 arg1 histochemistry 585:598 lectin histochemistry 578:598 lectin histochemistry 578:598 In this study, the expression of β1,6-GlcNAc branched N-glycans in nonneoplastic brain and glioma samples was characterized by lectin histochemistry. 26526581 6 32 theme β1,6-GlcNAc 693:703 arg1 branches 705:712 β1,6-GlcNAc branches 693:712 β1,6-GlcNAc branches 693:712 We found that β1,6-GlcNAc branches were highly expressed in glioblastoma specimens, compared with diffuse astrocytomas and nonneoplastic brain. 26526581 0 33 theme cells 35:39 arg1 Radiosensitisation 0:17 Radiosensitisation 0:17 Radiosensitisation of human glioma cells by inhibition of β1,6-GlcNAc 0:68 Radiosensitisation of human glioma cells by inhibition of β1,6-GlcNAc branched N-glycans. 26526581 4 34 theme glioma 542:547 arg1 samples 549:555 nonneoplastic brain and glioma samples 518:555 samples 549:555 In this study, the expression of β1,6-GlcNAc branched N-glycans in nonneoplastic brain and glioma samples was characterized by lectin histochemistry. 26526581 11 35 theme promising 1435:1443 arg1 strategy 1445:1452 a promising strategy 1433:1452 a promising strategy 1433:1452 Thus, our results suggest that development of therapeutic approaches targeting N-linked β1,6-GlcNAc branches may be a promising strategy in glioblastoma treatment. 26526581 11 35 theme promising 1435:1443 arg1 development 1348:1358 development 1348:1358 development of therapeutic approaches targeting N-linked β1,6-GlcNAc branches 1348:1424 Thus, our results suggest that development of therapeutic approaches targeting N-linked β1,6-GlcNAc branches may be a promising strategy in glioblastoma treatment. 26526581 0 36 theme glioma 28:33 arg1 cells 35:39 human glioma cells 22:39 human glioma cells 22:39 Radiosensitisation of human glioma cells by inhibition of β1,6-GlcNAc branched N-glycans. 26526581 9 37 theme apoptotic 1187:1195 arg1 cells 1197:1201 apoptotic cells 1187:1201 apoptotic cells 1187:1201 Meanwhile, the G2/M checkpoint was impaired and there was an increase in the number of apoptotic cells. 26526581 7 38 theme branched 848:855 arg1 expression 857:866 β1,6-GlcNAc branched expression 836:866 β1,6-GlcNAc branched expression 836:866 In addition, β1,6-GlcNAc branched expression was negatively correlated with the radiosensitivity of glioblastoma cells. 26526581 6 39 theme nonneoplastic 802:814 arg1 brain 816:820 nonneoplastic brain 802:820 nonneoplastic brain 802:820 We found that β1,6-GlcNAc branches were highly expressed in glioblastoma specimens, compared with diffuse astrocytomas and nonneoplastic brain. 26526581 1 40 theme prevalent 111:119 arg1 type 121:124 the most prevalent type 102:124 the most prevalent type of primary brain tumors 102:148 Gliomas are the most prevalent type of primary brain tumors and are resistant to radiation therapy. 26526581 1 40 theme prevalent 111:119 arg1 Gliomas 90:96 Gliomas 90:96 Gliomas 90:96 Gliomas are the most prevalent type of primary brain tumors and are resistant to radiation therapy. 26526581 3 41 theme glioma 420:425 arg1 cells 427:431 glioma cells 420:431 glioma cells 420:431 However, the relationship between β1,6-GlcNAc branched expression and radiosensitivity in glioma cells is still unknown. 26526581 8 42 link N-linked 974:981 arg1 branches 995:1002 N-linked β1,6-GlcNAc branches 974:1002 N-linked β1,6-GlcNAc branches 974:1002 Furthermore, the inhibition of N-linked β1,6-GlcNAc branches by GnT-V silencing in U251 cells could reduce the cell clonogenic survival after X-irradiation. 26526581 11 43 from strategy 1445:1452 arg1 treatment 1470:1478 glioblastoma treatment 1457:1478 glioblastoma treatment 1457:1478 Thus, our results suggest that development of therapeutic approaches targeting N-linked β1,6-GlcNAc branches may be a promising strategy in glioblastoma treatment. 26526581 11 44 theme approaches 1375:1384 arg1 strategy 1445:1452 a promising strategy 1433:1452 a promising strategy 1433:1452 Thus, our results suggest that development of therapeutic approaches targeting N-linked β1,6-GlcNAc branches may be a promising strategy in glioblastoma treatment. 26526581 11 44 theme approaches 1375:1384 arg1 development 1348:1358 development 1348:1358 development of therapeutic approaches targeting N-linked β1,6-GlcNAc branches 1348:1424 Thus, our results suggest that development of therapeutic approaches targeting N-linked β1,6-GlcNAc branches may be a promising strategy in glioblastoma treatment. 26526581 10 45 theme U251 1305:1308 arg1 cells 1310:1314 U251 cells 1305:1314 U251 cells 1305:1314 Tunicamycin, an inhibitor of N-glycan biosynthesis, was also able to enhance the radiosensitivity of U251 cells. 26526581 2 46 theme branched 202:209 arg1 N-glycans 211:219 β1,6-GlcNAc branched N-glycans 190:219 β1,6-GlcNAc branched N-glycans 190:219 β1,6-GlcNAc branched N-glycans, which are encoded by N-acetylglucosaminyltransferase V (GnT-V), play important roles in glioma progression. 26526581 8 47 theme GnT-V 1007:1011 arg1 silencing 1013:1021 GnT-V silencing 1007:1021 GnT-V silencing in U251 cells 1007:1035 Furthermore, the inhibition of N-linked β1,6-GlcNAc branches by GnT-V silencing in U251 cells could reduce the cell clonogenic survival after X-irradiation. 26526581 9 48 theme cells 1197:1201 arg1 number 1177:1182 the number 1173:1182 the number of apoptotic cells 1173:1201 Meanwhile, the G2/M checkpoint was impaired and there was an increase in the number of apoptotic cells. 26526581 2 49 theme β1,6-GlcNAc 190:200 arg1 N-glycans 211:219 β1,6-GlcNAc branched N-glycans 190:219 β1,6-GlcNAc branched N-glycans 190:219 β1,6-GlcNAc branched N-glycans, which are encoded by N-acetylglucosaminyltransferase V (GnT-V), play important roles in glioma progression. 26526581 7 50 theme cells 936:940 arg1 radiosensitivity 903:918 the radiosensitivity 899:918 the radiosensitivity of glioblastoma cells 899:940 In addition, β1,6-GlcNAc branched expression was negatively correlated with the radiosensitivity of glioblastoma cells. 26526581 6 51 theme diffuse 777:783 arg1 astrocytomas 785:796 diffuse astrocytomas 777:796 diffuse astrocytomas 777:796 We found that β1,6-GlcNAc branches were highly expressed in glioblastoma specimens, compared with diffuse astrocytomas and nonneoplastic brain. 26526581 1 52 theme primary 129:135 arg1 tumors 143:148 primary brain tumors 129:148 primary brain tumors 129:148 Gliomas are the most prevalent type of primary brain tumors and are resistant to radiation therapy. 26526581 11 53 theme glioblastoma 1457:1468 arg1 treatment 1470:1478 glioblastoma treatment 1457:1478 glioblastoma treatment 1457:1478 Thus, our results suggest that development of therapeutic approaches targeting N-linked β1,6-GlcNAc branches may be a promising strategy in glioblastoma treatment. 26526581 2 54 theme N-acetylglucosaminyltransferase 243:273 arg1 GnT-V 278:282 GnT-V 278:282 GnT-V 278:282 β1,6-GlcNAc branched N-glycans, which are encoded by N-acetylglucosaminyltransferase V (GnT-V), play important roles in glioma progression. 26526581 2 54 theme N-acetylglucosaminyltransferase 243:273 arg1 V 275:275 N-acetylglucosaminyltransferase V 243:275 N-acetylglucosaminyltransferase V (GnT-V) 243:283 β1,6-GlcNAc branched N-glycans, which are encoded by N-acetylglucosaminyltransferase V (GnT-V), play important roles in glioma progression. 26526581 11 55 link N-linked 1396:1403 arg1 branches 1417:1424 N-linked β1,6-GlcNAc branches 1396:1424 N-linked β1,6-GlcNAc branches 1396:1424 Thus, our results suggest that development of therapeutic approaches targeting N-linked β1,6-GlcNAc branches may be a promising strategy in glioblastoma treatment. 26526581 1 56 theme brain 137:141 arg1 tumors 143:148 primary brain tumors 129:148 primary brain tumors 129:148 Gliomas are the most prevalent type of primary brain tumors and are resistant to radiation therapy. 26526581 9 57 theme G2/M 1115:1118 arg1 Meanwhile 1100:1108 Meanwhile 1100:1108 Meanwhile 1100:1108 Meanwhile, the G2/M checkpoint was impaired and there was an increase in the number of apoptotic cells. 26526581 9 57 theme G2/M 1115:1118 arg1 checkpoint 1120:1129 the G2/M checkpoint 1111:1129 the G2/M checkpoint 1111:1129 Meanwhile, the G2/M checkpoint was impaired and there was an increase in the number of apoptotic cells. 26526581 10 58 theme biosynthesis 1242:1253 arg1 Tunicamycin 1204:1214 Tunicamycin 1204:1214 Tunicamycin 1204:1214 Tunicamycin, an inhibitor of N-glycan biosynthesis, was also able to enhance the radiosensitivity of U251 cells. 26526581 10 58 theme biosynthesis 1242:1253 arg1 inhibitor 1220:1228 an inhibitor 1217:1228 an inhibitor of N-glycan biosynthesis 1217:1253 Tunicamycin, an inhibitor of N-glycan biosynthesis, was also able to enhance the radiosensitivity of U251 cells. 26526581 0 59 theme β1,6-GlcNAc 58:68 arg1 inhibition 44:53 inhibition 44:53 inhibition of β1,6-GlcNAc 44:68 Radiosensitisation of human glioma cells by inhibition of β1,6-GlcNAc branched N-glycans. 26526581 11 60 theme N-linked 1396:1403 arg1 branches 1417:1424 N-linked β1,6-GlcNAc branches 1396:1424 N-linked β1,6-GlcNAc branches 1396:1424 Thus, our results suggest that development of therapeutic approaches targeting N-linked β1,6-GlcNAc branches may be a promising strategy in glioblastoma treatment. 26526581 1 61 theme tumors 143:148 arg1 type 121:124 the most prevalent type 102:124 the most prevalent type of primary brain tumors 102:148 Gliomas are the most prevalent type of primary brain tumors and are resistant to radiation therapy. 26526581 1 61 theme tumors 143:148 arg1 Gliomas 90:96 Gliomas 90:96 Gliomas 90:96 Gliomas are the most prevalent type of primary brain tumors and are resistant to radiation therapy. 26526581 10 62 theme N-glycan 1233:1240 arg1 biosynthesis 1242:1253 N-glycan biosynthesis 1233:1253 N-glycan biosynthesis 1233:1253 Tunicamycin, an inhibitor of N-glycan biosynthesis, was also able to enhance the radiosensitivity of U251 cells. 24967714 2 0 theme correct 417:423 arg1 expression 425:434 the correct expression 413:434 the correct expression of gp120 and gp41 in the virus particle 413:474 Of the, on average, 24 N-linked glycans present on gp120, the glycan at Asn260 was reported to be essential for the correct expression of gp120 and gp41 in the virus particle and deletion of the N260 glycan in gp120 heavily compromised virus infectivity. 24967714 3 1 theme Golgi 622:626 arg1 apparatus 628:636 the Golgi apparatus 618:636 the Golgi apparatus 618:636 We show here that gp160 containing the N260Q mutation reaches the Golgi apparatus during biosynthesis. 24967714 0 2 theme infectivity 148:158 arg1 loss 134:137 loss 134:137 loss of viral infectivity 134:158 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. 24967714 1 3 theme gp120 225:229 arg1 surface 191:197 the surface 187:197 the surface of the HIV-1 glycoprotein gp120 187:229 N-linked glycans covering the surface of the HIV-1 glycoprotein gp120 are of major importance for the correct folding of this glycoprotein. 24967714 0 4 theme gp120 61:65 arg1 Asn260 45:50 the highly conserved N-glycan at Asn260 12:50 the highly conserved N-glycan at Asn260 of HIV-1 gp120 12:65 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. 24967714 5 5 theme N260Q 1029:1033 arg1 virus 1041:1045 mutant N260Q gp120 virus 1022:1045 mutant N260Q gp120 virus 1022:1045 In the search of compensatory mutations, we found a mutation in the V1/V2 loop of gp120 (S128N) that could partially restore the infectivity of mutant N260Q gp120 virus. 24967714 0 6 theme viral 142:146 arg1 infectivity 148:158 viral infectivity 142:158 viral infectivity 142:158 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. 24967714 8 7 theme mutant 1635:1640 arg1 gp160 1642:1646 the wild-type or mutant gp160 1618:1646 the wild-type or mutant gp160 that is normally targeted for lysosomal degradation 1618:1698 Moreover, at least part of the wild-type or mutant gp160 that is normally targeted for lysosomal degradation reached a conformation that enabled CD4 binding. 24967714 7 8 from role 1468:1471 arg1 breakdown 1496:1504 the breakdown 1492:1504 the breakdown 1492:1504 Finally, we show that mutant N260Q gp160 was cleaved to gp120 and gp41 to a much lower extent than wild-type gp160, and that it was subject of lysosomal degradation to a higher extent than wild-type gp160 showing a prominent role of this process in the breakdown of N260-glycan-deleted gp160, which could not be counteracted by the S128N mutation. 24967714 2 9 from deletion 480:487 arg1 particle 467:474 the virus particle 457:474 the virus particle 457:474 Of the, on average, 24 N-linked glycans present on gp120, the glycan at Asn260 was reported to be essential for the correct expression of gp120 and gp41 in the virus particle and deletion of the N260 glycan in gp120 heavily compromised virus infectivity. 24967714 2 9 from deletion 480:487 arg1 gp120 511:515 gp120 511:515 gp120 511:515 Of the, on average, 24 N-linked glycans present on gp120, the glycan at Asn260 was reported to be essential for the correct expression of gp120 and gp41 in the virus particle and deletion of the N260 glycan in gp120 heavily compromised virus infectivity. 24967714 5 10 theme gp120 1035:1039 arg1 virus 1041:1045 mutant N260Q gp120 virus 1022:1045 mutant N260Q gp120 virus 1022:1045 In the search of compensatory mutations, we found a mutation in the V1/V2 loop of gp120 (S128N) that could partially restore the infectivity of mutant N260Q gp120 virus. 24967714 7 11 theme degradation 1396:1406 arg1 subject 1375:1381 subject 1375:1381 subject 1375:1381 Finally, we show that mutant N260Q gp160 was cleaved to gp120 and gp41 to a much lower extent than wild-type gp160, and that it was subject of lysosomal degradation to a higher extent than wild-type gp160 showing a prominent role of this process in the breakdown of N260-glycan-deleted gp160, which could not be counteracted by the S128N mutation. 24967714 2 12 theme gp41 449:452 arg1 expression 425:434 the correct expression 413:434 the correct expression of gp120 and gp41 in the virus particle 413:474 Of the, on average, 24 N-linked glycans present on gp120, the glycan at Asn260 was reported to be essential for the correct expression of gp120 and gp41 in the virus particle and deletion of the N260 glycan in gp120 heavily compromised virus infectivity. 24967714 2 12 theme gp41 449:452 arg1 deletion 480:487 deletion 480:487 deletion of the N260 glycan in gp120 480:515 Of the, on average, 24 N-linked glycans present on gp120, the glycan at Asn260 was reported to be essential for the correct expression of gp120 and gp41 in the virus particle and deletion of the N260 glycan in gp120 heavily compromised virus infectivity. 24967714 0 13 from Asn260 45:50 arg1 N-glycan 33:40 the highly conserved N-glycan at Asn260 12:50 the highly conserved N-glycan at Asn260 of HIV-1 gp120 12:65 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. 24967714 0 13 from Asn260 45:50 arg1 at 42:43 the highly conserved N-glycan at Asn260 12:50 the highly conserved N-glycan at Asn260 of HIV-1 gp120 12:65 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. 24967714 2 14 theme glycan 501:506 arg1 expression 425:434 the correct expression 413:434 the correct expression of gp120 and gp41 in the virus particle 413:474 Of the, on average, 24 N-linked glycans present on gp120, the glycan at Asn260 was reported to be essential for the correct expression of gp120 and gp41 in the virus particle and deletion of the N260 glycan in gp120 heavily compromised virus infectivity. 24967714 2 14 theme glycan 501:506 arg1 deletion 480:487 deletion 480:487 deletion of the N260 glycan in gp120 480:515 Of the, on average, 24 N-linked glycans present on gp120, the glycan at Asn260 was reported to be essential for the correct expression of gp120 and gp41 in the virus particle and deletion of the N260 glycan in gp120 heavily compromised virus infectivity. 24967714 1 15 gly glycoprotein 212:223 arg1 glycoprotein 212:223 the HIV-1 glycoprotein gp120 202:229 the HIV-1 glycoprotein gp120 202:229 N-linked glycans covering the surface of the HIV-1 glycoprotein gp120 are of major importance for the correct folding of this glycoprotein. 24967714 7 16 theme wild-type 1342:1350 arg1 gp160 1352:1356 wild-type gp160 1342:1356 wild-type gp160 1342:1356 Finally, we show that mutant N260Q gp160 was cleaved to gp120 and gp41 to a much lower extent than wild-type gp160, and that it was subject of lysosomal degradation to a higher extent than wild-type gp160 showing a prominent role of this process in the breakdown of N260-glycan-deleted gp160, which could not be counteracted by the S128N mutation. 24967714 1 17 theme major 238:242 arg1 importance 244:253 major importance 238:253 major importance 238:253 N-linked glycans covering the surface of the HIV-1 glycoprotein gp120 are of major importance for the correct folding of this glycoprotein. 24967714 6 18 theme compensatory 1147:1158 arg1 effect 1195:1200 a conformational effect 1178:1200 a conformational effect that does not affect CD4 binding per se 1178:1240 However, the mutation S128N did not enhance any of the above-mentioned processes so its underlying compensatory mechanism must be a conformational effect that does not affect CD4 binding per se. 24967714 6 18 theme compensatory 1147:1158 arg1 mechanism 1160:1168 its underlying compensatory mechanism 1132:1168 its underlying compensatory mechanism 1132:1168 However, the mutation S128N did not enhance any of the above-mentioned processes so its underlying compensatory mechanism must be a conformational effect that does not affect CD4 binding per se. 24967714 8 19 theme gp160 1642:1646 arg1 part 1610:1613 at least part 1601:1613 at least part of the wild-type or mutant gp160 that is normally targeted for lysosomal degradation 1601:1698 Moreover, at least part of the wild-type or mutant gp160 that is normally targeted for lysosomal degradation reached a conformation that enabled CD4 binding. 24967714 5 20 theme compensatory 895:906 arg1 mutations 908:916 compensatory mutations 895:916 compensatory mutations 895:916 In the search of compensatory mutations, we found a mutation in the V1/V2 loop of gp120 (S128N) that could partially restore the infectivity of mutant N260Q gp120 virus. 24967714 3 21 contain containing 580:589 arg2 mutation 601:608 the N260Q mutation 591:608 the N260Q mutation 591:608 We show here that gp160 containing the N260Q mutation reaches the Golgi apparatus during biosynthesis. 24967714 3 21 contain containing 580:589 arg1 gp160 574:578 gp160 574:578 gp160 containing the N260Q mutation 574:608 We show here that gp160 containing the N260Q mutation reaches the Golgi apparatus during biosynthesis. 24967714 0 22 theme lysosomal 87:95 arg1 degradation 97:107 lysosomal degradation 87:107 lysosomal degradation 87:107 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. 24967714 1 23 link N-linked 161:168 arg1 glycans 170:176 N-linked glycans 161:176 N-linked glycans covering the surface of the HIV-1 glycoprotein gp120 161:229 N-linked glycans covering the surface of the HIV-1 glycoprotein gp120 are of major importance for the correct folding of this glycoprotein. 24967714 5 24 theme mutations 908:916 arg1 search 885:890 the search 881:890 the search of compensatory mutations 881:916 In the search of compensatory mutations, we found a mutation in the V1/V2 loop of gp120 (S128N) that could partially restore the infectivity of mutant N260Q gp120 virus. 24967714 7 25 theme gp160 1529:1533 arg1 breakdown 1496:1504 the breakdown 1492:1504 the breakdown 1492:1504 Finally, we show that mutant N260Q gp160 was cleaved to gp120 and gp41 to a much lower extent than wild-type gp160, and that it was subject of lysosomal degradation to a higher extent than wild-type gp160 showing a prominent role of this process in the breakdown of N260-glycan-deleted gp160, which could not be counteracted by the S128N mutation. 24967714 2 26 theme present 341:347 arg1 average 312:318 average 312:318 average 312:318 Of the, on average, 24 N-linked glycans present on gp120, the glycan at Asn260 was reported to be essential for the correct expression of gp120 and gp41 in the virus particle and deletion of the N260 glycan in gp120 heavily compromised virus infectivity. 24967714 2 26 theme present 341:347 arg1 glycans 333:339 24 N-linked glycans 321:339 24 N-linked glycans present on gp120 321:356 Of the, on average, 24 N-linked glycans present on gp120, the glycan at Asn260 was reported to be essential for the correct expression of gp120 and gp41 in the virus particle and deletion of the N260 glycan in gp120 heavily compromised virus infectivity. 24967714 2 27 theme virus 537:541 arg1 infectivity 543:553 heavily compromised virus infectivity 517:553 heavily compromised virus infectivity 517:553 Of the, on average, 24 N-linked glycans present on gp120, the glycan at Asn260 was reported to be essential for the correct expression of gp120 and gp41 in the virus particle and deletion of the N260 glycan in gp120 heavily compromised virus infectivity. 24967714 4 28 theme pulse-chase 665:675 arg1 experiments 677:687 pulse-chase experiments 665:687 pulse-chase experiments with [35S] methionine/cysteine 665:718 Using pulse-chase experiments with [35S] methionine/cysteine, we show that oxidative folding was slightly delayed in case of mutant N260Q gp160 and that CD4 binding was markedly compromised compared to wild-type gp160. 24967714 7 29 theme lower 1324:1328 arg1 extent 1330:1335 a much lower extent 1317:1335 a much lower extent than wild-type gp160 1317:1356 Finally, we show that mutant N260Q gp160 was cleaved to gp120 and gp41 to a much lower extent than wild-type gp160, and that it was subject of lysosomal degradation to a higher extent than wild-type gp160 showing a prominent role of this process in the breakdown of N260-glycan-deleted gp160, which could not be counteracted by the S128N mutation. 24967714 4 30 theme wild-type 861:869 arg1 gp160 871:875 wild-type gp160 861:875 wild-type gp160 861:875 Using pulse-chase experiments with [35S] methionine/cysteine, we show that oxidative folding was slightly delayed in case of mutant N260Q gp160 and that CD4 binding was markedly compromised compared to wild-type gp160. 24967714 7 31 theme process 1481:1487 arg1 role 1468:1471 a prominent role 1456:1471 a prominent role of this process in the breakdown of N260-glycan-deleted gp160, which could not be counteracted by the S128N mutation 1456:1588 Finally, we show that mutant N260Q gp160 was cleaved to gp120 and gp41 to a much lower extent than wild-type gp160, and that it was subject of lysosomal degradation to a higher extent than wild-type gp160 showing a prominent role of this process in the breakdown of N260-glycan-deleted gp160, which could not be counteracted by the S128N mutation. 24967714 2 32 theme compromised 525:535 arg1 infectivity 543:553 heavily compromised virus infectivity 517:553 heavily compromised virus infectivity 517:553 Of the, on average, 24 N-linked glycans present on gp120, the glycan at Asn260 was reported to be essential for the correct expression of gp120 and gp41 in the virus particle and deletion of the N260 glycan in gp120 heavily compromised virus infectivity. 24967714 1 33 theme N-linked 161:168 arg1 glycans 170:176 N-linked glycans 161:176 N-linked glycans covering the surface of the HIV-1 glycoprotein gp120 161:229 N-linked glycans covering the surface of the HIV-1 glycoprotein gp120 are of major importance for the correct folding of this glycoprotein. 24967714 8 34 theme lysosomal 1678:1686 arg1 degradation 1688:1698 lysosomal degradation 1678:1698 lysosomal degradation 1678:1698 Moreover, at least part of the wild-type or mutant gp160 that is normally targeted for lysosomal degradation reached a conformation that enabled CD4 binding. 24967714 0 35 theme gp120 112:116 arg1 folding 75:81 folding 75:81 folding 75:81 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. 24967714 0 35 theme gp120 112:116 arg1 degradation 97:107 lysosomal degradation 87:107 lysosomal degradation 87:107 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. 24967714 4 36 theme N260Q 791:795 arg1 gp160 797:801 mutant N260Q gp160 784:801 mutant N260Q gp160 784:801 Using pulse-chase experiments with [35S] methionine/cysteine, we show that oxidative folding was slightly delayed in case of mutant N260Q gp160 and that CD4 binding was markedly compromised compared to wild-type gp160. 24967714 7 37 theme N260-glycan-deleted 1509:1527 arg1 gp160 1529:1533 N260-glycan-deleted gp160 1509:1533 N260-glycan-deleted gp160 1509:1533 Finally, we show that mutant N260Q gp160 was cleaved to gp120 and gp41 to a much lower extent than wild-type gp160, and that it was subject of lysosomal degradation to a higher extent than wild-type gp160 showing a prominent role of this process in the breakdown of N260-glycan-deleted gp160, which could not be counteracted by the S128N mutation. 24967714 2 38 theme glycan 363:368 arg1 essential 399:407 essential 399:407 essential 399:407 Of the, on average, 24 N-linked glycans present on gp120, the glycan at Asn260 was reported to be essential for the correct expression of gp120 and gp41 in the virus particle and deletion of the N260 glycan in gp120 heavily compromised virus infectivity. 24967714 2 38 theme glycan 363:368 arg1 Asn260 373:378 the glycan at Asn260 359:378 the glycan at Asn260 359:378 Of the, on average, 24 N-linked glycans present on gp120, the glycan at Asn260 was reported to be essential for the correct expression of gp120 and gp41 in the virus particle and deletion of the N260 glycan in gp120 heavily compromised virus infectivity. 24967714 2 39 theme at 370:371 arg1 essential 399:407 essential 399:407 essential 399:407 Of the, on average, 24 N-linked glycans present on gp120, the glycan at Asn260 was reported to be essential for the correct expression of gp120 and gp41 in the virus particle and deletion of the N260 glycan in gp120 heavily compromised virus infectivity. 24967714 2 39 theme at 370:371 arg1 Asn260 373:378 the glycan at Asn260 359:378 the glycan at Asn260 359:378 Of the, on average, 24 N-linked glycans present on gp120, the glycan at Asn260 was reported to be essential for the correct expression of gp120 and gp41 in the virus particle and deletion of the N260 glycan in gp120 heavily compromised virus infectivity. 24967714 5 40 theme mutant 1022:1027 arg1 virus 1041:1045 mutant N260Q gp120 virus 1022:1045 mutant N260Q gp120 virus 1022:1045 In the search of compensatory mutations, we found a mutation in the V1/V2 loop of gp120 (S128N) that could partially restore the infectivity of mutant N260Q gp120 virus. 24967714 6 41 theme mutation 1061:1068 arg1 S128N 1070:1074 the mutation S128N 1057:1074 the mutation S128N 1057:1074 However, the mutation S128N did not enhance any of the above-mentioned processes so its underlying compensatory mechanism must be a conformational effect that does not affect CD4 binding per se. 24967714 5 42 from mutation 930:937 arg1 loop 952:955 the V1/V2 loop 942:955 the V1/V2 loop of gp120 (S128N) 942:972 In the search of compensatory mutations, we found a mutation in the V1/V2 loop of gp120 (S128N) that could partially restore the infectivity of mutant N260Q gp120 virus. 24967714 0 43 theme N-glycan 33:40 arg1 Asn260 45:50 the highly conserved N-glycan at Asn260 12:50 the highly conserved N-glycan at Asn260 of HIV-1 gp120 12:65 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. 24967714 1 44 theme correct 263:269 arg1 folding 271:277 the correct folding 259:277 the correct folding of this glycoprotein 259:298 N-linked glycans covering the surface of the HIV-1 glycoprotein gp120 are of major importance for the correct folding of this glycoprotein. 24967714 2 45 theme virus 461:465 arg1 particle 467:474 the virus particle 457:474 the virus particle 457:474 Of the, on average, 24 N-linked glycans present on gp120, the glycan at Asn260 was reported to be essential for the correct expression of gp120 and gp41 in the virus particle and deletion of the N260 glycan in gp120 heavily compromised virus infectivity. 24967714 2 46 link N-linked 324:331 arg1 average 312:318 average 312:318 average 312:318 Of the, on average, 24 N-linked glycans present on gp120, the glycan at Asn260 was reported to be essential for the correct expression of gp120 and gp41 in the virus particle and deletion of the N260 glycan in gp120 heavily compromised virus infectivity. 24967714 2 46 link N-linked 324:331 arg1 glycans 333:339 24 N-linked glycans 321:339 24 N-linked glycans present on gp120 321:356 Of the, on average, 24 N-linked glycans present on gp120, the glycan at Asn260 was reported to be essential for the correct expression of gp120 and gp41 in the virus particle and deletion of the N260 glycan in gp120 heavily compromised virus infectivity. 24967714 6 47 theme conformational 1180:1193 arg1 effect 1195:1200 a conformational effect 1178:1200 a conformational effect that does not affect CD4 binding per se 1178:1240 However, the mutation S128N did not enhance any of the above-mentioned processes so its underlying compensatory mechanism must be a conformational effect that does not affect CD4 binding per se. 24967714 6 47 theme conformational 1180:1193 arg1 mechanism 1160:1168 its underlying compensatory mechanism 1132:1168 its underlying compensatory mechanism 1132:1168 However, the mutation S128N did not enhance any of the above-mentioned processes so its underlying compensatory mechanism must be a conformational effect that does not affect CD4 binding per se. 24967714 2 48 theme N-linked 324:331 arg1 average 312:318 average 312:318 average 312:318 Of the, on average, 24 N-linked glycans present on gp120, the glycan at Asn260 was reported to be essential for the correct expression of gp120 and gp41 in the virus particle and deletion of the N260 glycan in gp120 heavily compromised virus infectivity. 24967714 2 48 theme N-linked 324:331 arg1 glycans 333:339 24 N-linked glycans 321:339 24 N-linked glycans present on gp120 321:356 Of the, on average, 24 N-linked glycans present on gp120, the glycan at Asn260 was reported to be essential for the correct expression of gp120 and gp41 in the virus particle and deletion of the N260 glycan in gp120 heavily compromised virus infectivity. 24967714 0 49 theme conserved 23:31 arg1 Asn260 45:50 the highly conserved N-glycan at Asn260 12:50 the highly conserved N-glycan at Asn260 of HIV-1 gp120 12:65 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. 24967714 5 50 theme virus 1041:1045 arg1 infectivity 1007:1017 the infectivity 1003:1017 the infectivity of mutant N260Q gp120 virus 1003:1045 In the search of compensatory mutations, we found a mutation in the V1/V2 loop of gp120 (S128N) that could partially restore the infectivity of mutant N260Q gp120 virus. 24967714 7 51 theme higher 1413:1418 arg1 extent 1420:1425 a higher extent 1411:1425 a higher extent than wild-type gp160 showing a prominent role of this process in the breakdown of N260-glycan-deleted gp160, which could not be counteracted by the S128N mutation 1411:1588 Finally, we show that mutant N260Q gp160 was cleaved to gp120 and gp41 to a much lower extent than wild-type gp160, and that it was subject of lysosomal degradation to a higher extent than wild-type gp160 showing a prominent role of this process in the breakdown of N260-glycan-deleted gp160, which could not be counteracted by the S128N mutation. 24967714 6 52 theme CD4 1223:1225 arg1 binding 1227:1233 CD4 binding 1223:1233 CD4 binding 1223:1233 However, the mutation S128N did not enhance any of the above-mentioned processes so its underlying compensatory mechanism must be a conformational effect that does not affect CD4 binding per se. 24967714 7 53 theme mutant 1265:1270 arg1 gp160 1278:1282 mutant N260Q gp160 1265:1282 mutant N260Q gp160 1265:1282 Finally, we show that mutant N260Q gp160 was cleaved to gp120 and gp41 to a much lower extent than wild-type gp160, and that it was subject of lysosomal degradation to a higher extent than wild-type gp160 showing a prominent role of this process in the breakdown of N260-glycan-deleted gp160, which could not be counteracted by the S128N mutation. 24967714 2 54 theme gp120 439:443 arg1 expression 425:434 the correct expression 413:434 the correct expression of gp120 and gp41 in the virus particle 413:474 Of the, on average, 24 N-linked glycans present on gp120, the glycan at Asn260 was reported to be essential for the correct expression of gp120 and gp41 in the virus particle and deletion of the N260 glycan in gp120 heavily compromised virus infectivity. 24967714 2 54 theme gp120 439:443 arg1 deletion 480:487 deletion 480:487 deletion of the N260 glycan in gp120 480:515 Of the, on average, 24 N-linked glycans present on gp120, the glycan at Asn260 was reported to be essential for the correct expression of gp120 and gp41 in the virus particle and deletion of the N260 glycan in gp120 heavily compromised virus infectivity. 24967714 0 55 theme Asn260 45:50 arg1 Deletion 0:7 Deletion 0:7 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 0:65 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. 24967714 4 56 with experiments 677:687 arg1 methionine/cysteine 700:718 [35S] methionine/cysteine 694:718 [35S] methionine/cysteine 694:718 Using pulse-chase experiments with [35S] methionine/cysteine, we show that oxidative folding was slightly delayed in case of mutant N260Q gp160 and that CD4 binding was markedly compromised compared to wild-type gp160. 24967714 2 57 theme N260 496:499 arg1 glycan 501:506 the N260 glycan 492:506 the N260 glycan 492:506 Of the, on average, 24 N-linked glycans present on gp120, the glycan at Asn260 was reported to be essential for the correct expression of gp120 and gp41 in the virus particle and deletion of the N260 glycan in gp120 heavily compromised virus infectivity. 24967714 2 58 from expression 425:434 arg1 particle 467:474 the virus particle 457:474 the virus particle 457:474 Of the, on average, 24 N-linked glycans present on gp120, the glycan at Asn260 was reported to be essential for the correct expression of gp120 and gp41 in the virus particle and deletion of the N260 glycan in gp120 heavily compromised virus infectivity. 24967714 2 58 from expression 425:434 arg1 gp120 511:515 gp120 511:515 gp120 511:515 Of the, on average, 24 N-linked glycans present on gp120, the glycan at Asn260 was reported to be essential for the correct expression of gp120 and gp41 in the virus particle and deletion of the N260 glycan in gp120 heavily compromised virus infectivity. 24967714 6 59 theme above-mentioned 1103:1117 arg1 processes 1119:1127 the above-mentioned processes 1099:1127 the above-mentioned processes 1099:1127 However, the mutation S128N did not enhance any of the above-mentioned processes so its underlying compensatory mechanism must be a conformational effect that does not affect CD4 binding per se. 24967714 0 60 theme at 42:43 arg1 Asn260 45:50 the highly conserved N-glycan at Asn260 12:50 the highly conserved N-glycan at Asn260 of HIV-1 gp120 12:65 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. 24967714 4 61 theme CD4 812:814 arg1 binding 816:822 CD4 binding 812:822 CD4 binding 812:822 Using pulse-chase experiments with [35S] methionine/cysteine, we show that oxidative folding was slightly delayed in case of mutant N260Q gp160 and that CD4 binding was markedly compromised compared to wild-type gp160. 24967714 2 62 attach present 341:347 arg2 average 312:318 average 312:318 average 312:318 Of the, on average, 24 N-linked glycans present on gp120, the glycan at Asn260 was reported to be essential for the correct expression of gp120 and gp41 in the virus particle and deletion of the N260 glycan in gp120 heavily compromised virus infectivity. 24967714 2 62 attach present 341:347 arg1 gp120 352:356 gp120 352:356 gp120 352:356 Of the, on average, 24 N-linked glycans present on gp120, the glycan at Asn260 was reported to be essential for the correct expression of gp120 and gp41 in the virus particle and deletion of the N260 glycan in gp120 heavily compromised virus infectivity. 24967714 2 62 attach present 341:347 arg2 glycans 333:339 24 N-linked glycans 321:339 24 N-linked glycans present on gp120 321:356 Of the, on average, 24 N-linked glycans present on gp120, the glycan at Asn260 was reported to be essential for the correct expression of gp120 and gp41 in the virus particle and deletion of the N260 glycan in gp120 heavily compromised virus infectivity. 24967714 5 63 theme V1/V2 946:950 arg1 loop 952:955 the V1/V2 loop 942:955 the V1/V2 loop of gp120 (S128N) 942:972 In the search of compensatory mutations, we found a mutation in the V1/V2 loop of gp120 (S128N) that could partially restore the infectivity of mutant N260Q gp120 virus. 24967714 8 64 theme CD4 1736:1738 arg1 binding 1740:1746 CD4 binding 1736:1746 CD4 binding 1736:1746 Moreover, at least part of the wild-type or mutant gp160 that is normally targeted for lysosomal degradation reached a conformation that enabled CD4 binding. 24967714 7 65 theme lysosomal 1386:1394 arg1 degradation 1396:1406 lysosomal degradation 1386:1406 lysosomal degradation 1386:1406 Finally, we show that mutant N260Q gp160 was cleaved to gp120 and gp41 to a much lower extent than wild-type gp160, and that it was subject of lysosomal degradation to a higher extent than wild-type gp160 showing a prominent role of this process in the breakdown of N260-glycan-deleted gp160, which could not be counteracted by the S128N mutation. 24967714 1 66 theme glycoprotein 287:298 arg1 folding 271:277 the correct folding 259:277 the correct folding of this glycoprotein 259:298 N-linked glycans covering the surface of the HIV-1 glycoprotein gp120 are of major importance for the correct folding of this glycoprotein. 24967714 3 67 theme N260Q 595:599 arg1 mutation 601:608 the N260Q mutation 591:608 the N260Q mutation 591:608 We show here that gp160 containing the N260Q mutation reaches the Golgi apparatus during biosynthesis. 24967714 6 68 theme underlying 1136:1145 arg1 effect 1195:1200 a conformational effect 1178:1200 a conformational effect that does not affect CD4 binding per se 1178:1240 However, the mutation S128N did not enhance any of the above-mentioned processes so its underlying compensatory mechanism must be a conformational effect that does not affect CD4 binding per se. 24967714 6 68 theme underlying 1136:1145 arg1 mechanism 1160:1168 its underlying compensatory mechanism 1132:1168 its underlying compensatory mechanism 1132:1168 However, the mutation S128N did not enhance any of the above-mentioned processes so its underlying compensatory mechanism must be a conformational effect that does not affect CD4 binding per se. 24967714 7 69 theme N260Q 1272:1276 arg1 gp160 1278:1282 mutant N260Q gp160 1265:1282 mutant N260Q gp160 1265:1282 Finally, we show that mutant N260Q gp160 was cleaved to gp120 and gp41 to a much lower extent than wild-type gp160, and that it was subject of lysosomal degradation to a higher extent than wild-type gp160 showing a prominent role of this process in the breakdown of N260-glycan-deleted gp160, which could not be counteracted by the S128N mutation. 24967714 7 70 theme wild-type 1432:1440 arg1 gp160 1442:1446 wild-type gp160 1432:1446 wild-type gp160 showing a prominent role of this process in the breakdown of N260-glycan-deleted gp160, which could not be counteracted by the S128N mutation 1432:1588 Finally, we show that mutant N260Q gp160 was cleaved to gp120 and gp41 to a much lower extent than wild-type gp160, and that it was subject of lysosomal degradation to a higher extent than wild-type gp160 showing a prominent role of this process in the breakdown of N260-glycan-deleted gp160, which could not be counteracted by the S128N mutation. 24967714 2 71 dep expression 425:434 arg1 infectivity 543:553 heavily compromised virus infectivity 517:553 heavily compromised virus infectivity 517:553 Of the, on average, 24 N-linked glycans present on gp120, the glycan at Asn260 was reported to be essential for the correct expression of gp120 and gp41 in the virus particle and deletion of the N260 glycan in gp120 heavily compromised virus infectivity. 24967714 4 72 theme mutant 784:789 arg1 gp160 797:801 mutant N260Q gp160 784:801 mutant N260Q gp160 784:801 Using pulse-chase experiments with [35S] methionine/cysteine, we show that oxidative folding was slightly delayed in case of mutant N260Q gp160 and that CD4 binding was markedly compromised compared to wild-type gp160. 24967714 5 73 theme gp120 960:964 arg1 loop 952:955 the V1/V2 loop 942:955 the V1/V2 loop of gp120 (S128N) 942:972 In the search of compensatory mutations, we found a mutation in the V1/V2 loop of gp120 (S128N) that could partially restore the infectivity of mutant N260Q gp120 virus. 24967714 0 74 theme HIV-1 55:59 arg1 gp120 61:65 HIV-1 gp120 55:65 HIV-1 gp120 55:65 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. 24967714 4 75 theme oxidative 734:742 arg1 folding 744:750 oxidative folding 734:750 oxidative folding 734:750 Using pulse-chase experiments with [35S] methionine/cysteine, we show that oxidative folding was slightly delayed in case of mutant N260Q gp160 and that CD4 binding was markedly compromised compared to wild-type gp160. 24967714 8 76 theme wild-type 1622:1630 arg1 gp160 1642:1646 the wild-type or mutant gp160 1618:1646 the wild-type or mutant gp160 that is normally targeted for lysosomal degradation 1618:1698 Moreover, at least part of the wild-type or mutant gp160 that is normally targeted for lysosomal degradation reached a conformation that enabled CD4 binding. 24967714 7 77 theme S128N 1575:1579 arg1 mutation 1581:1588 the S128N mutation 1571:1588 the S128N mutation 1571:1588 Finally, we show that mutant N260Q gp160 was cleaved to gp120 and gp41 to a much lower extent than wild-type gp160, and that it was subject of lysosomal degradation to a higher extent than wild-type gp160 showing a prominent role of this process in the breakdown of N260-glycan-deleted gp160, which could not be counteracted by the S128N mutation. 24967714 1 78 theme HIV-1 206:210 arg1 gp120 225:229 the HIV-1 glycoprotein gp120 202:229 the HIV-1 glycoprotein gp120 202:229 N-linked glycans covering the surface of the HIV-1 glycoprotein gp120 are of major importance for the correct folding of this glycoprotein. 24967714 2 79 from Asn260 373:378 arg1 at 370:371 the glycan at Asn260 359:378 the glycan at Asn260 359:378 Of the, on average, 24 N-linked glycans present on gp120, the glycan at Asn260 was reported to be essential for the correct expression of gp120 and gp41 in the virus particle and deletion of the N260 glycan in gp120 heavily compromised virus infectivity. 24967714 2 79 from Asn260 373:378 arg1 glycan 363:368 the glycan at Asn260 359:378 the glycan at Asn260 359:378 Of the, on average, 24 N-linked glycans present on gp120, the glycan at Asn260 was reported to be essential for the correct expression of gp120 and gp41 in the virus particle and deletion of the N260 glycan in gp120 heavily compromised virus infectivity. 24967714 1 80 gly glycoprotein 287:298 arg1 glycoprotein 287:298 this glycoprotein 282:298 this glycoprotein 282:298 N-linked glycans covering the surface of the HIV-1 glycoprotein gp120 are of major importance for the correct folding of this glycoprotein. 24967714 4 81 dep methionine/cysteine 700:718 arg1 [35S 694:697 [35S 694:697 [35S 694:697 Using pulse-chase experiments with [35S] methionine/cysteine, we show that oxidative folding was slightly delayed in case of mutant N260Q gp160 and that CD4 binding was markedly compromised compared to wild-type gp160. 24967714 7 82 theme prominent 1458:1466 arg1 role 1468:1471 a prominent role 1456:1471 a prominent role of this process in the breakdown of N260-glycan-deleted gp160, which could not be counteracted by the S128N mutation 1456:1588 Finally, we show that mutant N260Q gp160 was cleaved to gp120 and gp41 to a much lower extent than wild-type gp160, and that it was subject of lysosomal degradation to a higher extent than wild-type gp160 showing a prominent role of this process in the breakdown of N260-glycan-deleted gp160, which could not be counteracted by the S128N mutation. 24967714 1 83 theme glycoprotein 212:223 arg1 gp120 225:229 the HIV-1 glycoprotein gp120 202:229 the HIV-1 glycoprotein gp120 202:229 N-linked glycans covering the surface of the HIV-1 glycoprotein gp120 are of major importance for the correct folding of this glycoprotein. 28207759 6 0 theme simultaneous 1131:1142 arg1 detection 1144:1152 simultaneous detection 1131:1152 simultaneous detection of different GBAs by paired measurements 1131:1193 We comparatively studied binding and uptake of ABP-labeled imiglucerase and velaglucerase in isolated dendritic cells, cultured human macrophages and living mice, through simultaneous detection of different GBAs by paired measurements. 28207759 10 1 theme significant 1554:1564 arg1 differences 1566:1576 Small, but significant differences 1543:1576 Small, but significant differences 1543:1576 Small, but significant differences were noted in binding and uptake of rGBAs in cultured human macrophages, in the absence and presence of mannan. 28207759 15 2 with trace-labeled 2329:2341 arg1 ABP 2351:2353 an ABP 2348:2353 an ABP 2348:2353 Our study suggests that further insight in targeting and efficacy of enzyme therapy of individual Gaucher patients could be obtained by the use of recombinant GBA, trace-labeled with an ABP, preferably equipped with an infrared fluorophore or other reporter tag suitable for in vivo imaging. 28207759 13 3 theme multiple 1993:2000 arg1 receptors 2002:2010 multiple receptors 1993:2010 multiple receptors 1993:2010 Uptake of recombinant GBAs by cultured macrophages seems to involve multiple receptors, including several mannose-binding lectins. 28207759 2 4 theme macrophages 302:312 arg1 lysosomes 280:288 the lysosomes 276:288 the lysosomes of visceral macrophages 276:312 In the common non-neuronopathic GD type I variant, glucosylceramide accumulates primarily in the lysosomes of visceral macrophages. 28207759 9 5 theme severe 1484:1489 arg1 types 1494:1498 severe GD types II and III 1484:1509 severe GD types II and III 1484:1509 Lungs, brain and skin, affected tissues in severe GD types II and III, were only poorly supplemented. 28207759 9 5 theme severe 1484:1489 arg1 III 1507:1509 III 1507:1509 III 1507:1509 Lungs, brain and skin, affected tissues in severe GD types II and III, were only poorly supplemented. 28207759 9 5 theme severe 1484:1489 arg1 II 1500:1501 II 1500:1501 II 1500:1501 Lungs, brain and skin, affected tissues in severe GD types II and III, were only poorly supplemented. 28207759 4 6 theme Man 733:735 arg1 glycans 740:746 Man(3) glycans 733:746 Man(3) glycans 733:746 Two recombinant GBA preparations with distinct N-linked glycans are registered in Europe for treatment of type I GD: imiglucerase (Genzyme), contains predominantly Man(3) glycans, and velaglucerase (Shire PLC) Man(9) glycans. 28207759 5 7 theme covalent 898:905 arg1 attachment 907:916 their covalent attachment 892:916 their covalent attachment to the catalytic nucleophile E340 of GBA 892:957 Activity-based probes (ABPs) enable fluorescent labeling of recombinant GBA preparations through their covalent attachment to the catalytic nucleophile E340 of GBA. 28207759 4 8 with preparations 589:600 arg1 glycans 625:631 distinct N-linked glycans 607:631 distinct N-linked glycans 607:631 Two recombinant GBA preparations with distinct N-linked glycans are registered in Europe for treatment of type I GD: imiglucerase (Genzyme), contains predominantly Man(3) glycans, and velaglucerase (Shire PLC) Man(9) glycans. 28207759 3 9 link N-linked 467:474 arg1 glycans 476:482 mannose-terminated N-linked glycans 448:482 mannose-terminated N-linked glycans 448:482 Supplementing storage cells with lacking enzyme is accomplished via chronic intravenous administration of recombinant GBA containing mannose-terminated N-linked glycans, mediating the selective uptake by macrophages expressing mannose-binding lectin(s). 28207759 5 10 theme GBA 867:869 arg1 preparations 871:882 recombinant GBA preparations 855:882 recombinant GBA preparations 855:882 Activity-based probes (ABPs) enable fluorescent labeling of recombinant GBA preparations through their covalent attachment to the catalytic nucleophile E340 of GBA. 28207759 10 11 theme human 1632:1636 arg1 macrophages 1638:1648 cultured human macrophages 1623:1648 cultured human macrophages 1623:1648 Small, but significant differences were noted in binding and uptake of rGBAs in cultured human macrophages, in the absence and presence of mannan. 28207759 15 12 theme enzyme 2234:2239 arg1 therapy 2241:2247 enzyme therapy 2234:2247 enzyme therapy 2234:2247 Our study suggests that further insight in targeting and efficacy of enzyme therapy of individual Gaucher patients could be obtained by the use of recombinant GBA, trace-labeled with an ABP, preferably equipped with an infrared fluorophore or other reporter tag suitable for in vivo imaging. 28207759 5 13 theme GBA 955:957 arg1 E340 947:950 the catalytic nucleophile E340 921:950 the catalytic nucleophile E340 of GBA 921:957 Activity-based probes (ABPs) enable fluorescent labeling of recombinant GBA preparations through their covalent attachment to the catalytic nucleophile E340 of GBA. 28207759 6 14 theme dendritic 1062:1070 arg1 cells 1072:1076 isolated dendritic cells 1053:1076 isolated dendritic cells 1053:1076 We comparatively studied binding and uptake of ABP-labeled imiglucerase and velaglucerase in isolated dendritic cells, cultured human macrophages and living mice, through simultaneous detection of different GBAs by paired measurements. 28207759 13 15 theme GBAs 1947:1950 arg1 Uptake 1925:1930 Uptake 1925:1930 Uptake of recombinant GBAs by cultured macrophages 1925:1974 Uptake of recombinant GBAs by cultured macrophages seems to involve multiple receptors, including several mannose-binding lectins. 28207759 0 16 theme fluorescent 80:90 arg1 probes 107:112 fluorescent activity-based probes 80:112 fluorescent activity-based probes 80:112 Investigations on therapeutic glucocerebrosidases through paired detection with fluorescent activity-based probes. 28207759 15 17 theme suitable 2427:2434 arg1 tag 2423:2425 an infrared fluorophore or other reporter tag 2381:2425 an infrared fluorophore or other reporter tag suitable for in vivo imaging 2381:2454 Our study suggests that further insight in targeting and efficacy of enzyme therapy of individual Gaucher patients could be obtained by the use of recombinant GBA, trace-labeled with an ABP, preferably equipped with an infrared fluorophore or other reporter tag suitable for in vivo imaging. 28207759 0 18 theme therapeutic 18:28 arg1 glucocerebrosidases 30:48 therapeutic glucocerebrosidases 18:48 therapeutic glucocerebrosidases 18:48 Investigations on therapeutic glucocerebrosidases through paired detection with fluorescent activity-based probes. 28207759 15 19 theme in 2440:2441 arg1 imaging 2448:2454 in vivo imaging 2440:2454 in vivo imaging 2440:2454 Our study suggests that further insight in targeting and efficacy of enzyme therapy of individual Gaucher patients could be obtained by the use of recombinant GBA, trace-labeled with an ABP, preferably equipped with an infrared fluorophore or other reporter tag suitable for in vivo imaging. 28207759 3 20 theme lacking 348:354 arg1 enzyme 356:361 lacking enzyme 348:361 lacking enzyme 348:361 Supplementing storage cells with lacking enzyme is accomplished via chronic intravenous administration of recombinant GBA containing mannose-terminated N-linked glycans, mediating the selective uptake by macrophages expressing mannose-binding lectin(s). 28207759 14 21 theme = 2105:2105 arg1 n 2103:2103 n = 12 2103:2108 n = 12 2103:2108 Differences among cells from different donors (n = 12) were noted, but the same trends were always observed. 28207759 14 21 theme = 2105:2105 arg1 donors 2095:2100 different donors 2085:2100 different donors (n = 12) 2085:2109 Differences among cells from different donors (n = 12) were noted, but the same trends were always observed. 28207759 15 22 theme reporter 2414:2421 arg1 tag 2423:2425 an infrared fluorophore or other reporter tag 2381:2425 an infrared fluorophore or other reporter tag suitable for in vivo imaging 2381:2454 Our study suggests that further insight in targeting and efficacy of enzyme therapy of individual Gaucher patients could be obtained by the use of recombinant GBA, trace-labeled with an ABP, preferably equipped with an infrared fluorophore or other reporter tag suitable for in vivo imaging. 28207759 5 23 theme catalytic 925:933 arg1 E340 947:950 the catalytic nucleophile E340 921:950 the catalytic nucleophile E340 of GBA 921:957 Activity-based probes (ABPs) enable fluorescent labeling of recombinant GBA preparations through their covalent attachment to the catalytic nucleophile E340 of GBA. 28207759 3 24 theme intravenous 391:401 arg1 administration 403:416 chronic intravenous administration 383:416 chronic intravenous administration of recombinant GBA containing mannose-terminated N-linked glycans, mediating the selective uptake by macrophages expressing mannose-binding lectin(s) 383:566 Supplementing storage cells with lacking enzyme is accomplished via chronic intravenous administration of recombinant GBA containing mannose-terminated N-linked glycans, mediating the selective uptake by macrophages expressing mannose-binding lectin(s). 28207759 0 25 from Investigations 0:13 arg1 glucocerebrosidases 30:48 therapeutic glucocerebrosidases 18:48 therapeutic glucocerebrosidases 18:48 Investigations on therapeutic glucocerebrosidases through paired detection with fluorescent activity-based probes. 28207759 15 26 from insight 2197:2203 arg1 efficacy 2222:2229 efficacy 2222:2229 efficacy 2222:2229 Our study suggests that further insight in targeting and efficacy of enzyme therapy of individual Gaucher patients could be obtained by the use of recombinant GBA, trace-labeled with an ABP, preferably equipped with an infrared fluorophore or other reporter tag suitable for in vivo imaging. 28207759 15 26 from insight 2197:2203 arg1 targeting 2208:2216 targeting 2208:2216 targeting 2208:2216 Our study suggests that further insight in targeting and efficacy of enzyme therapy of individual Gaucher patients could be obtained by the use of recombinant GBA, trace-labeled with an ABP, preferably equipped with an infrared fluorophore or other reporter tag suitable for in vivo imaging. 28207759 6 27 theme ABP-labeled 1007:1017 arg1 imiglucerase 1019:1030 ABP-labeled imiglucerase 1007:1030 ABP-labeled imiglucerase 1007:1030 We comparatively studied binding and uptake of ABP-labeled imiglucerase and velaglucerase in isolated dendritic cells, cultured human macrophages and living mice, through simultaneous detection of different GBAs by paired measurements. 28207759 8 28 theme bone 1417:1420 arg1 marrow 1422:1427 bone marrow 1417:1427 bone marrow 1417:1427 ABP-labeled rGBAs were recovered largely in liver, white-blood cells, bone marrow and spleen. 28207759 3 29 theme selective 499:507 arg1 uptake 509:514 the selective uptake 495:514 the selective uptake by macrophages expressing mannose-binding lectin(s) 495:566 Supplementing storage cells with lacking enzyme is accomplished via chronic intravenous administration of recombinant GBA containing mannose-terminated N-linked glycans, mediating the selective uptake by macrophages expressing mannose-binding lectin(s). 28207759 15 30 theme infrared 2384:2391 arg1 tag 2423:2425 an infrared fluorophore or other reporter tag 2381:2425 an infrared fluorophore or other reporter tag suitable for in vivo imaging 2381:2454 Our study suggests that further insight in targeting and efficacy of enzyme therapy of individual Gaucher patients could be obtained by the use of recombinant GBA, trace-labeled with an ABP, preferably equipped with an infrared fluorophore or other reporter tag suitable for in vivo imaging. 28207759 3 31 theme GBA 433:435 arg1 administration 403:416 chronic intravenous administration 383:416 chronic intravenous administration of recombinant GBA containing mannose-terminated N-linked glycans, mediating the selective uptake by macrophages expressing mannose-binding lectin(s) 383:566 Supplementing storage cells with lacking enzyme is accomplished via chronic intravenous administration of recombinant GBA containing mannose-terminated N-linked glycans, mediating the selective uptake by macrophages expressing mannose-binding lectin(s). 28207759 1 32 theme Gaucher 161:167 arg1 GD 178:179 GD 178:179 GD 178:179 Deficiency of glucocerebrosidase (GBA) causes Gaucher disease (GD). 28207759 1 32 theme Gaucher 161:167 arg1 disease 169:175 Gaucher disease 161:175 Gaucher disease (GD) 161:180 Deficiency of glucocerebrosidase (GBA) causes Gaucher disease (GD). 28207759 4 33 theme PLC 774:776 arg1 9 783:783 9 783:783 9 783:783 Two recombinant GBA preparations with distinct N-linked glycans are registered in Europe for treatment of type I GD: imiglucerase (Genzyme), contains predominantly Man(3) glycans, and velaglucerase (Shire PLC) Man(9) glycans. 28207759 4 33 theme PLC 774:776 arg1 Man 779:781 velaglucerase (Shire PLC) Man 753:781 velaglucerase (Shire PLC) Man(9) glycans 753:792 Two recombinant GBA preparations with distinct N-linked glycans are registered in Europe for treatment of type I GD: imiglucerase (Genzyme), contains predominantly Man(3) glycans, and velaglucerase (Shire PLC) Man(9) glycans. 28207759 7 34 theme dendritic 1227:1235 arg1 cells 1237:1241 dendritic cells 1227:1241 dendritic cells 1227:1241 Uptake of ABP-labeled rGBAs by dendritic cells was comparable, as well as the bio-distribution following equimolar intravenous administration to mice. 28207759 4 35 theme Man 779:781 arg1 glycans 786:792 velaglucerase (Shire PLC) Man(9) glycans 753:792 velaglucerase (Shire PLC) Man(9) glycans 753:792 Two recombinant GBA preparations with distinct N-linked glycans are registered in Europe for treatment of type I GD: imiglucerase (Genzyme), contains predominantly Man(3) glycans, and velaglucerase (Shire PLC) Man(9) glycans. 28207759 5 36 theme fluorescent 831:841 arg1 labeling 843:850 fluorescent labeling 831:850 fluorescent labeling of recombinant GBA preparations 831:882 Activity-based probes (ABPs) enable fluorescent labeling of recombinant GBA preparations through their covalent attachment to the catalytic nucleophile E340 of GBA. 28207759 15 37 theme patients 2271:2278 arg1 efficacy 2222:2229 efficacy 2222:2229 efficacy 2222:2229 Our study suggests that further insight in targeting and efficacy of enzyme therapy of individual Gaucher patients could be obtained by the use of recombinant GBA, trace-labeled with an ABP, preferably equipped with an infrared fluorophore or other reporter tag suitable for in vivo imaging. 28207759 15 37 theme patients 2271:2278 arg1 targeting 2208:2216 targeting 2208:2216 targeting 2208:2216 Our study suggests that further insight in targeting and efficacy of enzyme therapy of individual Gaucher patients could be obtained by the use of recombinant GBA, trace-labeled with an ABP, preferably equipped with an infrared fluorophore or other reporter tag suitable for in vivo imaging. 28207759 9 38 from tissues 1473:1479 arg1 types 1494:1498 severe GD types II and III 1484:1509 severe GD types II and III 1484:1509 Lungs, brain and skin, affected tissues in severe GD types II and III, were only poorly supplemented. 28207759 9 38 from tissues 1473:1479 arg1 III 1507:1509 III 1507:1509 III 1507:1509 Lungs, brain and skin, affected tissues in severe GD types II and III, were only poorly supplemented. 28207759 9 38 from tissues 1473:1479 arg1 II 1500:1501 II 1500:1501 II 1500:1501 Lungs, brain and skin, affected tissues in severe GD types II and III, were only poorly supplemented. 28207759 6 39 theme human 1088:1092 arg1 macrophages 1094:1104 cultured human macrophages 1079:1104 cultured human macrophages 1079:1104 We comparatively studied binding and uptake of ABP-labeled imiglucerase and velaglucerase in isolated dendritic cells, cultured human macrophages and living mice, through simultaneous detection of different GBAs by paired measurements. 28207759 10 40 theme mannan 1682:1687 arg1 presence 1670:1677 presence 1670:1677 presence 1670:1677 Small, but significant differences were noted in binding and uptake of rGBAs in cultured human macrophages, in the absence and presence of mannan. 28207759 10 40 theme mannan 1682:1687 arg1 absence 1658:1664 absence 1658:1664 absence 1658:1664 Small, but significant differences were noted in binding and uptake of rGBAs in cultured human macrophages, in the absence and presence of mannan. 28207759 5 41 theme Activity-based 795:808 arg1 probes 810:815 Activity-based probes 795:815 Activity-based probes (ABPs) 795:822 Activity-based probes (ABPs) enable fluorescent labeling of recombinant GBA preparations through their covalent attachment to the catalytic nucleophile E340 of GBA. 28207759 5 41 theme Activity-based 795:808 arg1 ABPs 818:821 ABPs 818:821 ABPs 818:821 Activity-based probes (ABPs) enable fluorescent labeling of recombinant GBA preparations through their covalent attachment to the catalytic nucleophile E340 of GBA. 28207759 15 42 theme individual 2252:2261 arg1 patients 2271:2278 individual Gaucher patients 2252:2278 individual Gaucher patients 2252:2278 Our study suggests that further insight in targeting and efficacy of enzyme therapy of individual Gaucher patients could be obtained by the use of recombinant GBA, trace-labeled with an ABP, preferably equipped with an infrared fluorophore or other reporter tag suitable for in vivo imaging. 28207759 3 43 theme mannose-terminated 448:465 arg1 glycans 476:482 mannose-terminated N-linked glycans 448:482 mannose-terminated N-linked glycans 448:482 Supplementing storage cells with lacking enzyme is accomplished via chronic intravenous administration of recombinant GBA containing mannose-terminated N-linked glycans, mediating the selective uptake by macrophages expressing mannose-binding lectin(s). 28207759 15 44 theme therapy 2241:2247 arg1 efficacy 2222:2229 efficacy 2222:2229 efficacy 2222:2229 Our study suggests that further insight in targeting and efficacy of enzyme therapy of individual Gaucher patients could be obtained by the use of recombinant GBA, trace-labeled with an ABP, preferably equipped with an infrared fluorophore or other reporter tag suitable for in vivo imaging. 28207759 15 44 theme therapy 2241:2247 arg1 targeting 2208:2216 targeting 2208:2216 targeting 2208:2216 Our study suggests that further insight in targeting and efficacy of enzyme therapy of individual Gaucher patients could be obtained by the use of recombinant GBA, trace-labeled with an ABP, preferably equipped with an infrared fluorophore or other reporter tag suitable for in vivo imaging. 28207759 10 45 from binding 1592:1598 arg1 macrophages 1638:1648 cultured human macrophages 1623:1648 cultured human macrophages 1623:1648 Small, but significant differences were noted in binding and uptake of rGBAs in cultured human macrophages, in the absence and presence of mannan. 28207759 4 46 theme distinct 607:614 arg1 glycans 625:631 distinct N-linked glycans 607:631 distinct N-linked glycans 607:631 Two recombinant GBA preparations with distinct N-linked glycans are registered in Europe for treatment of type I GD: imiglucerase (Genzyme), contains predominantly Man(3) glycans, and velaglucerase (Shire PLC) Man(9) glycans. 28207759 10 47 theme Small 1543:1547 arg1 differences 1566:1576 Small, but significant differences 1543:1576 Small, but significant differences 1543:1576 Small, but significant differences were noted in binding and uptake of rGBAs in cultured human macrophages, in the absence and presence of mannan. 28207759 2 48 theme type 218:221 arg1 variant 225:231 the common non-neuronopathic GD type I variant 186:231 the common non-neuronopathic GD type I variant 186:231 In the common non-neuronopathic GD type I variant, glucosylceramide accumulates primarily in the lysosomes of visceral macrophages. 28207759 10 49 dep absence 1658:1664 arg1 the 1654:1656 the 1654:1656 the 1654:1656 Small, but significant differences were noted in binding and uptake of rGBAs in cultured human macrophages, in the absence and presence of mannan. 28207759 10 50 from uptake 1604:1609 arg1 macrophages 1638:1648 cultured human macrophages 1623:1648 cultured human macrophages 1623:1648 Small, but significant differences were noted in binding and uptake of rGBAs in cultured human macrophages, in the absence and presence of mannan. 28207759 6 51 theme different 1157:1165 arg1 GBAs 1167:1170 different GBAs 1157:1170 different GBAs 1157:1170 We comparatively studied binding and uptake of ABP-labeled imiglucerase and velaglucerase in isolated dendritic cells, cultured human macrophages and living mice, through simultaneous detection of different GBAs by paired measurements. 28207759 4 52 theme type 675:678 arg1 treatment 662:670 treatment 662:670 treatment of type I GD 662:683 Two recombinant GBA preparations with distinct N-linked glycans are registered in Europe for treatment of type I GD: imiglucerase (Genzyme), contains predominantly Man(3) glycans, and velaglucerase (Shire PLC) Man(9) glycans. 28207759 4 53 contain contains 710:717 arg2 glycans 786:792 velaglucerase (Shire PLC) Man(9) glycans 753:792 velaglucerase (Shire PLC) Man(9) glycans 753:792 Two recombinant GBA preparations with distinct N-linked glycans are registered in Europe for treatment of type I GD: imiglucerase (Genzyme), contains predominantly Man(3) glycans, and velaglucerase (Shire PLC) Man(9) glycans. 28207759 4 53 contain contains 710:717 arg1 Genzyme 700:706 Genzyme 700:706 Genzyme 700:706 Two recombinant GBA preparations with distinct N-linked glycans are registered in Europe for treatment of type I GD: imiglucerase (Genzyme), contains predominantly Man(3) glycans, and velaglucerase (Shire PLC) Man(9) glycans. 28207759 4 53 contain contains 710:717 arg1 imiglucerase 686:697 imiglucerase 686:697 imiglucerase (Genzyme) 686:707 Two recombinant GBA preparations with distinct N-linked glycans are registered in Europe for treatment of type I GD: imiglucerase (Genzyme), contains predominantly Man(3) glycans, and velaglucerase (Shire PLC) Man(9) glycans. 28207759 4 53 contain contains 710:717 arg2 glycans 740:746 Man(3) glycans 733:746 Man(3) glycans 733:746 Two recombinant GBA preparations with distinct N-linked glycans are registered in Europe for treatment of type I GD: imiglucerase (Genzyme), contains predominantly Man(3) glycans, and velaglucerase (Shire PLC) Man(9) glycans. 28207759 0 54 with detection 65:73 arg1 probes 107:112 fluorescent activity-based probes 80:112 fluorescent activity-based probes 80:112 Investigations on therapeutic glucocerebrosidases through paired detection with fluorescent activity-based probes. 28207759 15 55 theme recombinant 2312:2322 arg1 GBA 2324:2326 recombinant GBA 2312:2326 recombinant GBA 2312:2326 Our study suggests that further insight in targeting and efficacy of enzyme therapy of individual Gaucher patients could be obtained by the use of recombinant GBA, trace-labeled with an ABP, preferably equipped with an infrared fluorophore or other reporter tag suitable for in vivo imaging. 28207759 7 56 theme intravenous 1311:1321 arg1 administration 1323:1336 equimolar intravenous administration 1301:1336 equimolar intravenous administration to mice 1301:1344 Uptake of ABP-labeled rGBAs by dendritic cells was comparable, as well as the bio-distribution following equimolar intravenous administration to mice. 28207759 14 57 from donors 2095:2100 arg1 cells 2074:2078 cells 2074:2078 cells from different donors (n = 12) 2074:2109 Differences among cells from different donors (n = 12) were noted, but the same trends were always observed. 28207759 13 58 theme mannose-binding 2031:2045 arg1 lectins 2047:2053 several mannose-binding lectins 2023:2053 several mannose-binding lectins 2023:2053 Uptake of recombinant GBAs by cultured macrophages seems to involve multiple receptors, including several mannose-binding lectins. 28207759 9 59 theme affected 1464:1471 arg1 Lungs 1441:1445 Lungs 1441:1445 Lungs 1441:1445 Lungs, brain and skin, affected tissues in severe GD types II and III, were only poorly supplemented. 28207759 9 59 theme affected 1464:1471 arg1 tissues 1473:1479 affected tissues 1464:1479 affected tissues in severe GD types II and III 1464:1509 Lungs, brain and skin, affected tissues in severe GD types II and III, were only poorly supplemented. 28207759 4 60 link N-linked 616:623 arg1 glycans 625:631 distinct N-linked glycans 607:631 distinct N-linked glycans 607:631 Two recombinant GBA preparations with distinct N-linked glycans are registered in Europe for treatment of type I GD: imiglucerase (Genzyme), contains predominantly Man(3) glycans, and velaglucerase (Shire PLC) Man(9) glycans. 28207759 11 61 theme Mannan-competed 1690:1704 arg1 binding 1706:1712 Mannan-competed binding 1690:1712 Mannan-competed binding 1690:1712 Mannan-competed binding and uptake were largest for velaglucerase, when determined with single enzymes or as equimolar mixtures of both enzymes. 28207759 2 62 theme visceral 293:300 arg1 macrophages 302:312 visceral macrophages 293:312 visceral macrophages 293:312 In the common non-neuronopathic GD type I variant, glucosylceramide accumulates primarily in the lysosomes of visceral macrophages. 28207759 5 63 theme preparations 871:882 arg1 labeling 843:850 fluorescent labeling 831:850 fluorescent labeling of recombinant GBA preparations 831:882 Activity-based probes (ABPs) enable fluorescent labeling of recombinant GBA preparations through their covalent attachment to the catalytic nucleophile E340 of GBA. 28207759 10 64 theme cultured 1623:1630 arg1 macrophages 1638:1648 cultured human macrophages 1623:1648 cultured human macrophages 1623:1648 Small, but significant differences were noted in binding and uptake of rGBAs in cultured human macrophages, in the absence and presence of mannan. 28207759 13 65 theme cultured 1955:1962 arg1 macrophages 1964:1974 cultured macrophages 1955:1974 cultured macrophages 1955:1974 Uptake of recombinant GBAs by cultured macrophages seems to involve multiple receptors, including several mannose-binding lectins. 28207759 9 66 theme GD 1491:1492 arg1 types 1494:1498 severe GD types II and III 1484:1509 severe GD types II and III 1484:1509 Lungs, brain and skin, affected tissues in severe GD types II and III, were only poorly supplemented. 28207759 9 66 theme GD 1491:1492 arg1 III 1507:1509 III 1507:1509 III 1507:1509 Lungs, brain and skin, affected tissues in severe GD types II and III, were only poorly supplemented. 28207759 9 66 theme GD 1491:1492 arg1 II 1500:1501 II 1500:1501 II 1500:1501 Lungs, brain and skin, affected tissues in severe GD types II and III, were only poorly supplemented. 28207759 3 67 contain containing 437:446 arg1 GBA 433:435 recombinant GBA 421:435 recombinant GBA containing mannose-terminated N-linked glycans, mediating the selective uptake by macrophages expressing mannose-binding lectin(s) 421:566 Supplementing storage cells with lacking enzyme is accomplished via chronic intravenous administration of recombinant GBA containing mannose-terminated N-linked glycans, mediating the selective uptake by macrophages expressing mannose-binding lectin(s). 28207759 3 67 contain containing 437:446 arg2 glycans 476:482 mannose-terminated N-linked glycans 448:482 mannose-terminated N-linked glycans 448:482 Supplementing storage cells with lacking enzyme is accomplished via chronic intravenous administration of recombinant GBA containing mannose-terminated N-linked glycans, mediating the selective uptake by macrophages expressing mannose-binding lectin(s). 28207759 10 68 theme rGBAs 1614:1618 arg1 binding 1592:1598 binding 1592:1598 binding 1592:1598 Small, but significant differences were noted in binding and uptake of rGBAs in cultured human macrophages, in the absence and presence of mannan. 28207759 10 68 theme rGBAs 1614:1618 arg1 uptake 1604:1609 uptake 1604:1609 uptake 1604:1609 Small, but significant differences were noted in binding and uptake of rGBAs in cultured human macrophages, in the absence and presence of mannan. 28207759 11 69 theme enzymes 1826:1832 arg1 mixtures 1809:1816 equimolar mixtures 1799:1816 equimolar mixtures of both enzymes 1799:1832 Mannan-competed binding and uptake were largest for velaglucerase, when determined with single enzymes or as equimolar mixtures of both enzymes. 28207759 5 70 theme recombinant 855:865 arg1 preparations 871:882 recombinant GBA preparations 855:882 recombinant GBA preparations 855:882 Activity-based probes (ABPs) enable fluorescent labeling of recombinant GBA preparations through their covalent attachment to the catalytic nucleophile E340 of GBA. 28207759 5 71 theme nucleophile 935:945 arg1 E340 947:950 the catalytic nucleophile E340 921:950 the catalytic nucleophile E340 of GBA 921:957 Activity-based probes (ABPs) enable fluorescent labeling of recombinant GBA preparations through their covalent attachment to the catalytic nucleophile E340 of GBA. 28207759 4 72 theme recombinant 573:583 arg1 preparations 589:600 Two recombinant GBA preparations 569:600 Two recombinant GBA preparations with distinct N-linked glycans 569:631 Two recombinant GBA preparations with distinct N-linked glycans are registered in Europe for treatment of type I GD: imiglucerase (Genzyme), contains predominantly Man(3) glycans, and velaglucerase (Shire PLC) Man(9) glycans. 28207759 8 73 theme ABP-labeled 1347:1357 arg1 rGBAs 1359:1363 ABP-labeled rGBAs 1347:1363 ABP-labeled rGBAs 1347:1363 ABP-labeled rGBAs were recovered largely in liver, white-blood cells, bone marrow and spleen. 28207759 3 74 theme storage 329:335 arg1 cells 337:341 storage cells 329:341 storage cells 329:341 Supplementing storage cells with lacking enzyme is accomplished via chronic intravenous administration of recombinant GBA containing mannose-terminated N-linked glycans, mediating the selective uptake by macrophages expressing mannose-binding lectin(s). 28207759 4 75 theme velaglucerase 753:765 arg1 9 783:783 9 783:783 9 783:783 Two recombinant GBA preparations with distinct N-linked glycans are registered in Europe for treatment of type I GD: imiglucerase (Genzyme), contains predominantly Man(3) glycans, and velaglucerase (Shire PLC) Man(9) glycans. 28207759 4 75 theme velaglucerase 753:765 arg1 Man 779:781 velaglucerase (Shire PLC) Man 753:781 velaglucerase (Shire PLC) Man(9) glycans 753:792 Two recombinant GBA preparations with distinct N-linked glycans are registered in Europe for treatment of type I GD: imiglucerase (Genzyme), contains predominantly Man(3) glycans, and velaglucerase (Shire PLC) Man(9) glycans. 28207759 13 76 theme recombinant 1935:1945 arg1 GBAs 1947:1950 recombinant GBAs 1935:1950 recombinant GBAs 1935:1950 Uptake of recombinant GBAs by cultured macrophages seems to involve multiple receptors, including several mannose-binding lectins. 28207759 11 77 theme single 1778:1783 arg1 enzymes 1785:1791 single enzymes 1778:1791 single enzymes 1778:1791 Mannan-competed binding and uptake were largest for velaglucerase, when determined with single enzymes or as equimolar mixtures of both enzymes. 28207759 0 78 theme activity-based 92:105 arg1 probes 107:112 fluorescent activity-based probes 80:112 fluorescent activity-based probes 80:112 Investigations on therapeutic glucocerebrosidases through paired detection with fluorescent activity-based probes. 28207759 4 79 dep type 675:678 arg1 GD 682:683 GD 682:683 type I GD 675:683 Two recombinant GBA preparations with distinct N-linked glycans are registered in Europe for treatment of type I GD: imiglucerase (Genzyme), contains predominantly Man(3) glycans, and velaglucerase (Shire PLC) Man(9) glycans. 28207759 6 80 theme isolated 1053:1060 arg1 cells 1072:1076 isolated dendritic cells 1053:1076 isolated dendritic cells 1053:1076 We comparatively studied binding and uptake of ABP-labeled imiglucerase and velaglucerase in isolated dendritic cells, cultured human macrophages and living mice, through simultaneous detection of different GBAs by paired measurements. 28207759 15 81 theme further 2189:2195 arg1 insight 2197:2203 further insight 2189:2203 further insight in targeting and efficacy of enzyme therapy of individual Gaucher patients 2189:2278 Our study suggests that further insight in targeting and efficacy of enzyme therapy of individual Gaucher patients could be obtained by the use of recombinant GBA, trace-labeled with an ABP, preferably equipped with an infrared fluorophore or other reporter tag suitable for in vivo imaging. 28207759 6 82 theme velaglucerase 1036:1048 arg1 uptake 997:1002 uptake 997:1002 uptake 997:1002 We comparatively studied binding and uptake of ABP-labeled imiglucerase and velaglucerase in isolated dendritic cells, cultured human macrophages and living mice, through simultaneous detection of different GBAs by paired measurements. 28207759 6 82 theme velaglucerase 1036:1048 arg1 binding 985:991 binding 985:991 binding 985:991 We comparatively studied binding and uptake of ABP-labeled imiglucerase and velaglucerase in isolated dendritic cells, cultured human macrophages and living mice, through simultaneous detection of different GBAs by paired measurements. 28207759 4 83 theme GBA 585:587 arg1 preparations 589:600 Two recombinant GBA preparations 569:600 Two recombinant GBA preparations with distinct N-linked glycans 569:631 Two recombinant GBA preparations with distinct N-linked glycans are registered in Europe for treatment of type I GD: imiglucerase (Genzyme), contains predominantly Man(3) glycans, and velaglucerase (Shire PLC) Man(9) glycans. 28207759 14 84 theme same 2131:2134 arg1 trends 2136:2141 the same trends 2127:2141 the same trends 2127:2141 Differences among cells from different donors (n = 12) were noted, but the same trends were always observed. 28207759 11 85 theme equimolar 1799:1807 arg1 mixtures 1809:1816 equimolar mixtures 1799:1816 equimolar mixtures of both enzymes 1799:1832 Mannan-competed binding and uptake were largest for velaglucerase, when determined with single enzymes or as equimolar mixtures of both enzymes. 28207759 6 86 theme imiglucerase 1019:1030 arg1 uptake 997:1002 uptake 997:1002 uptake 997:1002 We comparatively studied binding and uptake of ABP-labeled imiglucerase and velaglucerase in isolated dendritic cells, cultured human macrophages and living mice, through simultaneous detection of different GBAs by paired measurements. 28207759 6 86 theme imiglucerase 1019:1030 arg1 binding 985:991 binding 985:991 binding 985:991 We comparatively studied binding and uptake of ABP-labeled imiglucerase and velaglucerase in isolated dendritic cells, cultured human macrophages and living mice, through simultaneous detection of different GBAs by paired measurements. 28207759 8 87 theme white-blood 1398:1408 arg1 cells 1410:1414 white-blood cells 1398:1414 white-blood cells 1398:1414 ABP-labeled rGBAs were recovered largely in liver, white-blood cells, bone marrow and spleen. 28207759 15 88 theme other 2408:2412 arg1 tag 2423:2425 an infrared fluorophore or other reporter tag 2381:2425 an infrared fluorophore or other reporter tag suitable for in vivo imaging 2381:2454 Our study suggests that further insight in targeting and efficacy of enzyme therapy of individual Gaucher patients could be obtained by the use of recombinant GBA, trace-labeled with an ABP, preferably equipped with an infrared fluorophore or other reporter tag suitable for in vivo imaging. 28207759 3 89 theme chronic 383:389 arg1 administration 403:416 chronic intravenous administration 383:416 chronic intravenous administration of recombinant GBA containing mannose-terminated N-linked glycans, mediating the selective uptake by macrophages expressing mannose-binding lectin(s) 383:566 Supplementing storage cells with lacking enzyme is accomplished via chronic intravenous administration of recombinant GBA containing mannose-terminated N-linked glycans, mediating the selective uptake by macrophages expressing mannose-binding lectin(s). 28207759 15 90 theme fluorophore 2393:2403 arg1 tag 2423:2425 an infrared fluorophore or other reporter tag 2381:2425 an infrared fluorophore or other reporter tag suitable for in vivo imaging 2381:2454 Our study suggests that further insight in targeting and efficacy of enzyme therapy of individual Gaucher patients could be obtained by the use of recombinant GBA, trace-labeled with an ABP, preferably equipped with an infrared fluorophore or other reporter tag suitable for in vivo imaging. 28207759 6 91 theme living 1110:1115 arg1 mice 1117:1120 living mice 1110:1120 living mice 1110:1120 We comparatively studied binding and uptake of ABP-labeled imiglucerase and velaglucerase in isolated dendritic cells, cultured human macrophages and living mice, through simultaneous detection of different GBAs by paired measurements. 28207759 2 92 theme non-neuronopathic 197:213 arg1 variant 225:231 the common non-neuronopathic GD type I variant 186:231 the common non-neuronopathic GD type I variant 186:231 In the common non-neuronopathic GD type I variant, glucosylceramide accumulates primarily in the lysosomes of visceral macrophages. 28207759 4 93 theme Shire 768:772 arg1 9 783:783 9 783:783 9 783:783 Two recombinant GBA preparations with distinct N-linked glycans are registered in Europe for treatment of type I GD: imiglucerase (Genzyme), contains predominantly Man(3) glycans, and velaglucerase (Shire PLC) Man(9) glycans. 28207759 4 93 theme Shire 768:772 arg1 Man 779:781 velaglucerase (Shire PLC) Man 753:781 velaglucerase (Shire PLC) Man(9) glycans 753:792 Two recombinant GBA preparations with distinct N-linked glycans are registered in Europe for treatment of type I GD: imiglucerase (Genzyme), contains predominantly Man(3) glycans, and velaglucerase (Shire PLC) Man(9) glycans. 28207759 15 94 dep in 2440:2441 arg1 vivo 2443:2446 vivo 2443:2446 vivo 2443:2446 Our study suggests that further insight in targeting and efficacy of enzyme therapy of individual Gaucher patients could be obtained by the use of recombinant GBA, trace-labeled with an ABP, preferably equipped with an infrared fluorophore or other reporter tag suitable for in vivo imaging. 28207759 7 95 theme ABP-labeled 1206:1216 arg1 rGBAs 1218:1222 ABP-labeled rGBAs 1206:1222 ABP-labeled rGBAs 1206:1222 Uptake of ABP-labeled rGBAs by dendritic cells was comparable, as well as the bio-distribution following equimolar intravenous administration to mice. 28207759 1 96 theme glucocerebrosidase 129:146 arg1 Deficiency 115:124 Deficiency 115:124 Deficiency of glucocerebrosidase (GBA) 115:152 Deficiency of glucocerebrosidase (GBA) causes Gaucher disease (GD). 28207759 3 97 theme recombinant 421:431 arg1 GBA 433:435 recombinant GBA 421:435 recombinant GBA containing mannose-terminated N-linked glycans, mediating the selective uptake by macrophages expressing mannose-binding lectin(s) 421:566 Supplementing storage cells with lacking enzyme is accomplished via chronic intravenous administration of recombinant GBA containing mannose-terminated N-linked glycans, mediating the selective uptake by macrophages expressing mannose-binding lectin(s). 28207759 6 98 from binding 985:991 arg1 macrophages 1094:1104 cultured human macrophages 1079:1104 cultured human macrophages 1079:1104 We comparatively studied binding and uptake of ABP-labeled imiglucerase and velaglucerase in isolated dendritic cells, cultured human macrophages and living mice, through simultaneous detection of different GBAs by paired measurements. 28207759 6 98 from binding 985:991 arg1 mice 1117:1120 living mice 1110:1120 living mice 1110:1120 We comparatively studied binding and uptake of ABP-labeled imiglucerase and velaglucerase in isolated dendritic cells, cultured human macrophages and living mice, through simultaneous detection of different GBAs by paired measurements. 28207759 6 98 from binding 985:991 arg1 cells 1072:1076 isolated dendritic cells 1053:1076 isolated dendritic cells 1053:1076 We comparatively studied binding and uptake of ABP-labeled imiglucerase and velaglucerase in isolated dendritic cells, cultured human macrophages and living mice, through simultaneous detection of different GBAs by paired measurements. 28207759 2 99 theme common 190:195 arg1 variant 225:231 the common non-neuronopathic GD type I variant 186:231 the common non-neuronopathic GD type I variant 186:231 In the common non-neuronopathic GD type I variant, glucosylceramide accumulates primarily in the lysosomes of visceral macrophages. 28207759 3 100 theme mannose-binding 542:556 arg1 s 565:565 s 565:565 s 565:565 Supplementing storage cells with lacking enzyme is accomplished via chronic intravenous administration of recombinant GBA containing mannose-terminated N-linked glycans, mediating the selective uptake by macrophages expressing mannose-binding lectin(s). 28207759 3 100 theme mannose-binding 542:556 arg1 lectin 558:563 mannose-binding lectin 542:563 mannose-binding lectin(s) 542:566 Supplementing storage cells with lacking enzyme is accomplished via chronic intravenous administration of recombinant GBA containing mannose-terminated N-linked glycans, mediating the selective uptake by macrophages expressing mannose-binding lectin(s). 28207759 0 101 theme paired 58:63 arg1 detection 65:73 paired detection 58:73 paired detection with fluorescent activity-based probes 58:112 Investigations on therapeutic glucocerebrosidases through paired detection with fluorescent activity-based probes. 28207759 6 102 theme cultured 1079:1086 arg1 macrophages 1094:1104 cultured human macrophages 1079:1104 cultured human macrophages 1079:1104 We comparatively studied binding and uptake of ABP-labeled imiglucerase and velaglucerase in isolated dendritic cells, cultured human macrophages and living mice, through simultaneous detection of different GBAs by paired measurements. 28207759 6 103 from uptake 997:1002 arg1 macrophages 1094:1104 cultured human macrophages 1079:1104 cultured human macrophages 1079:1104 We comparatively studied binding and uptake of ABP-labeled imiglucerase and velaglucerase in isolated dendritic cells, cultured human macrophages and living mice, through simultaneous detection of different GBAs by paired measurements. 28207759 6 103 from uptake 997:1002 arg1 mice 1117:1120 living mice 1110:1120 living mice 1110:1120 We comparatively studied binding and uptake of ABP-labeled imiglucerase and velaglucerase in isolated dendritic cells, cultured human macrophages and living mice, through simultaneous detection of different GBAs by paired measurements. 28207759 6 103 from uptake 997:1002 arg1 cells 1072:1076 isolated dendritic cells 1053:1076 isolated dendritic cells 1053:1076 We comparatively studied binding and uptake of ABP-labeled imiglucerase and velaglucerase in isolated dendritic cells, cultured human macrophages and living mice, through simultaneous detection of different GBAs by paired measurements. 28207759 9 104 dep types 1494:1498 arg1 types 1494:1498 severe GD types II and III 1484:1509 severe GD types II and III 1484:1509 Lungs, brain and skin, affected tissues in severe GD types II and III, were only poorly supplemented. 28207759 9 104 dep types 1494:1498 arg1 III 1507:1509 III 1507:1509 III 1507:1509 Lungs, brain and skin, affected tissues in severe GD types II and III, were only poorly supplemented. 28207759 9 104 dep types 1494:1498 arg1 II 1500:1501 II 1500:1501 II 1500:1501 Lungs, brain and skin, affected tissues in severe GD types II and III, were only poorly supplemented. 28207759 15 105 theme Gaucher 2263:2269 arg1 patients 2271:2278 individual Gaucher patients 2252:2278 individual Gaucher patients 2252:2278 Our study suggests that further insight in targeting and efficacy of enzyme therapy of individual Gaucher patients could be obtained by the use of recombinant GBA, trace-labeled with an ABP, preferably equipped with an infrared fluorophore or other reporter tag suitable for in vivo imaging. 28207759 6 106 theme paired 1175:1180 arg1 measurements 1182:1193 paired measurements 1175:1193 paired measurements 1175:1193 We comparatively studied binding and uptake of ABP-labeled imiglucerase and velaglucerase in isolated dendritic cells, cultured human macrophages and living mice, through simultaneous detection of different GBAs by paired measurements. 28207759 3 107 theme N-linked 467:474 arg1 glycans 476:482 mannose-terminated N-linked glycans 448:482 mannose-terminated N-linked glycans 448:482 Supplementing storage cells with lacking enzyme is accomplished via chronic intravenous administration of recombinant GBA containing mannose-terminated N-linked glycans, mediating the selective uptake by macrophages expressing mannose-binding lectin(s). 28207759 4 108 theme N-linked 616:623 arg1 glycans 625:631 distinct N-linked glycans 607:631 distinct N-linked glycans 607:631 Two recombinant GBA preparations with distinct N-linked glycans are registered in Europe for treatment of type I GD: imiglucerase (Genzyme), contains predominantly Man(3) glycans, and velaglucerase (Shire PLC) Man(9) glycans. 28207759 14 109 theme different 2085:2093 arg1 n 2103:2103 n = 12 2103:2108 n = 12 2103:2108 Differences among cells from different donors (n = 12) were noted, but the same trends were always observed. 28207759 14 109 theme different 2085:2093 arg1 donors 2095:2100 different donors 2085:2100 different donors (n = 12) 2085:2109 Differences among cells from different donors (n = 12) were noted, but the same trends were always observed. 28207759 2 110 theme I 223:223 arg1 variant 225:231 the common non-neuronopathic GD type I variant 186:231 the common non-neuronopathic GD type I variant 186:231 In the common non-neuronopathic GD type I variant, glucosylceramide accumulates primarily in the lysosomes of visceral macrophages. 28207759 12 111 theme prominent 1872:1880 arg1 binding 1882:1888 more prominent binding 1867:1888 more prominent binding 1867:1888 Vice versa, imiglucerase showed more prominent binding and uptake not competed by mannan. 28207759 6 112 theme GBAs 1167:1170 arg1 detection 1144:1152 simultaneous detection 1131:1152 simultaneous detection of different GBAs by paired measurements 1131:1193 We comparatively studied binding and uptake of ABP-labeled imiglucerase and velaglucerase in isolated dendritic cells, cultured human macrophages and living mice, through simultaneous detection of different GBAs by paired measurements. 28207759 2 113 theme GD 215:216 arg1 variant 225:231 the common non-neuronopathic GD type I variant 186:231 the common non-neuronopathic GD type I variant 186:231 In the common non-neuronopathic GD type I variant, glucosylceramide accumulates primarily in the lysosomes of visceral macrophages. 28207759 7 114 theme equimolar 1301:1309 arg1 administration 1323:1336 equimolar intravenous administration 1301:1336 equimolar intravenous administration to mice 1301:1344 Uptake of ABP-labeled rGBAs by dendritic cells was comparable, as well as the bio-distribution following equimolar intravenous administration to mice. 28207759 13 115 theme several 2023:2029 arg1 lectins 2047:2053 several mannose-binding lectins 2023:2053 several mannose-binding lectins 2023:2053 Uptake of recombinant GBAs by cultured macrophages seems to involve multiple receptors, including several mannose-binding lectins. 28207759 7 116 theme rGBAs 1218:1222 arg1 Uptake 1196:1201 Uptake 1196:1201 Uptake of ABP-labeled rGBAs by dendritic cells 1196:1241 Uptake of ABP-labeled rGBAs by dendritic cells was comparable, as well as the bio-distribution following equimolar intravenous administration to mice. 28207759 15 117 theme GBA 2324:2326 arg1 use 2305:2307 the use 2301:2307 the use of recombinant GBA 2301:2326 Our study suggests that further insight in targeting and efficacy of enzyme therapy of individual Gaucher patients could be obtained by the use of recombinant GBA, trace-labeled with an ABP, preferably equipped with an infrared fluorophore or other reporter tag suitable for in vivo imaging. 28167250 1 0 theme important 249:257 arg1 role 259:262 an important role 246:262 an important role 246:262 Protein asparagine (N)-linked glycosylation is a post-translational modification that occurs in the endoplasmic reticulum; it plays an important role in protein folding, oligomerization, quality control, sorting, and transport. 28167250 4 1 theme DHDDS 923:927 arg1 function 929:936 DHDDS function 923:936 DHDDS function 923:936 Mutations in DHDDS were shown to result in retinitis pigmentosa, ultimately leading to blindness, but the exact molecular mechanism by which the mutations affect DHDDS function remains elusive. 28167250 11 2 theme novel 1904:1908 arg1 approaches 1922:1931 novel therapeutic approaches 1904:1931 novel therapeutic approaches 1904:1931 Future structural and functional studies of the recombinant DHDDS may shed light on the mechanisms underlying DHDDS-related retinitis pigmentosa and lead to novel therapeutic approaches. 28167250 3 3 theme N-linked 737:744 arg1 glycosylation 746:758 N-linked glycosylation 737:758 N-linked glycosylation 737:758 Dehydrodolichyl diphosphate synthase (DHDDS) is an eukaryotic cis prenyltransferase (cis-PT) that catalyzes chain elongation of farnesyl diphosphate via multiple condensations with isopentenyl diphosphate to form dehydrodolichyl diphosphate, a precursor for the glycosyl carrier dolichylpyrophophate involved in N-linked glycosylation. 28167250 5 4 theme antibacterial 1079:1091 arg1 agents 1093:1098 new antibacterial agents 1075:1098 new antibacterial agents 1075:1098 In addition, bacterial cis-PT homologs are involved in bacterial wall synthesis and are therefore potential targets for new antibacterial agents. 28167250 5 5 theme bacterial 1010:1018 arg1 synthesis 1025:1033 bacterial wall synthesis 1010:1033 bacterial wall synthesis 1010:1033 In addition, bacterial cis-PT homologs are involved in bacterial wall synthesis and are therefore potential targets for new antibacterial agents. 28167250 6 6 theme specific 1234:1241 arg1 drugs 1243:1247 prokaryotic cis-PT specific drugs 1215:1247 prokaryotic cis-PT specific drugs 1215:1247 However, as eukaryotic cis-PT were not thoroughly characterized structurally and functionally, rational design of prokaryotic cis-PT specific drugs is currently impossible. 28167250 4 7 theme retinitis 804:812 arg1 pigmentosa 814:823 retinitis pigmentosa 804:823 retinitis pigmentosa 804:823 Mutations in DHDDS were shown to result in retinitis pigmentosa, ultimately leading to blindness, but the exact molecular mechanism by which the mutations affect DHDDS function remains elusive. 28167250 8 8 theme similar 1477:1483 arg1 homodimer 1466:1474 a stable homodimer 1457:1474 a stable homodimer 1457:1474 The purified protein forms a stable homodimer, similar to its bacterial homologs, and shows time- and substrate-dependent activity. 28167250 3 9 theme farnesyl 553:560 arg1 diphosphate 562:572 farnesyl diphosphate 553:572 farnesyl diphosphate 553:572 Dehydrodolichyl diphosphate synthase (DHDDS) is an eukaryotic cis prenyltransferase (cis-PT) that catalyzes chain elongation of farnesyl diphosphate via multiple condensations with isopentenyl diphosphate to form dehydrodolichyl diphosphate, a precursor for the glycosyl carrier dolichylpyrophophate involved in N-linked glycosylation. 28167250 1 10 theme protein 267:273 arg1 folding 275:281 protein folding 267:281 protein folding 267:281 Protein asparagine (N)-linked glycosylation is a post-translational modification that occurs in the endoplasmic reticulum; it plays an important role in protein folding, oligomerization, quality control, sorting, and transport. 28167250 8 11 theme bacterial 1492:1500 arg1 homologs 1502:1509 its bacterial homologs 1488:1509 its bacterial homologs 1488:1509 The purified protein forms a stable homodimer, similar to its bacterial homologs, and shows time- and substrate-dependent activity. 28167250 3 12 theme chain 533:537 arg1 elongation 539:548 chain elongation 533:548 chain elongation of farnesyl diphosphate 533:572 Dehydrodolichyl diphosphate synthase (DHDDS) is an eukaryotic cis prenyltransferase (cis-PT) that catalyzes chain elongation of farnesyl diphosphate via multiple condensations with isopentenyl diphosphate to form dehydrodolichyl diphosphate, a precursor for the glycosyl carrier dolichylpyrophophate involved in N-linked glycosylation. 28167250 5 13 theme bacterial 968:976 arg1 homologs 985:992 bacterial cis-PT homologs 968:992 bacterial cis-PT homologs 968:992 In addition, bacterial cis-PT homologs are involved in bacterial wall synthesis and are therefore potential targets for new antibacterial agents. 28167250 1 14 theme post-translational 163:180 arg1 glycosylation 144:156 Protein asparagine (N)-linked glycosylation 114:156 Protein asparagine (N)-linked glycosylation 114:156 Protein asparagine (N)-linked glycosylation is a post-translational modification that occurs in the endoplasmic reticulum; it plays an important role in protein folding, oligomerization, quality control, sorting, and transport. 28167250 1 14 theme post-translational 163:180 arg1 modification 182:193 a post-translational modification 161:193 a post-translational modification that occurs in the endoplasmic reticulum 161:234 Protein asparagine (N)-linked glycosylation is a post-translational modification that occurs in the endoplasmic reticulum; it plays an important role in protein folding, oligomerization, quality control, sorting, and transport. 28167250 11 15 theme functional 1769:1778 arg1 studies 1780:1786 Future structural and functional studies 1747:1786 Future structural and functional studies of the recombinant DHDDS 1747:1811 Future structural and functional studies of the recombinant DHDDS may shed light on the mechanisms underlying DHDDS-related retinitis pigmentosa and lead to novel therapeutic approaches. 28167250 10 16 theme cis-PT 1739:1744 arg1 overexpression 1704:1717 the overexpression 1700:1717 the overexpression of other eukaryotic cis-PT 1700:1744 The protocol described here may be utilized for the overexpression of other eukaryotic cis-PT. 28167250 6 17 theme drugs 1243:1247 arg1 design 1205:1210 rational design 1196:1210 rational design of prokaryotic cis-PT specific drugs 1196:1247 However, as eukaryotic cis-PT were not thoroughly characterized structurally and functionally, rational design of prokaryotic cis-PT specific drugs is currently impossible. 28167250 7 18 theme non-denaturating 1367:1382 arg1 conditions 1384:1393 non-denaturating conditions 1367:1393 non-denaturating conditions using a codon-optimized construct 1367:1427 Here, we present a simple protocol for purification of functionally active human DHDDS under non-denaturating conditions using a codon-optimized construct. 28167250 3 19 theme multiple 578:585 arg1 condensations 587:599 multiple condensations 578:599 multiple condensations with isopentenyl diphosphate 578:628 Dehydrodolichyl diphosphate synthase (DHDDS) is an eukaryotic cis prenyltransferase (cis-PT) that catalyzes chain elongation of farnesyl diphosphate via multiple condensations with isopentenyl diphosphate to form dehydrodolichyl diphosphate, a precursor for the glycosyl carrier dolichylpyrophophate involved in N-linked glycosylation. 28167250 7 20 theme human 1349:1353 arg1 DHDDS 1355:1359 functionally active human DHDDS 1329:1359 functionally active human DHDDS 1329:1359 Here, we present a simple protocol for purification of functionally active human DHDDS under non-denaturating conditions using a codon-optimized construct. 28167250 3 21 theme Dehydrodolichyl 425:439 arg1 synthase 453:460 Dehydrodolichyl diphosphate synthase 425:460 Dehydrodolichyl diphosphate synthase (DHDDS) 425:468 Dehydrodolichyl diphosphate synthase (DHDDS) is an eukaryotic cis prenyltransferase (cis-PT) that catalyzes chain elongation of farnesyl diphosphate via multiple condensations with isopentenyl diphosphate to form dehydrodolichyl diphosphate, a precursor for the glycosyl carrier dolichylpyrophophate involved in N-linked glycosylation. 28167250 3 21 theme Dehydrodolichyl 425:439 arg1 prenyltransferase 491:507 an eukaryotic cis prenyltransferase 473:507 an eukaryotic cis prenyltransferase (cis-PT) that catalyzes chain elongation of farnesyl diphosphate via multiple condensations with isopentenyl diphosphate to form dehydrodolichyl diphosphate, a precursor for the glycosyl carrier dolichylpyrophophate involved in N-linked glycosylation 473:758 Dehydrodolichyl diphosphate synthase (DHDDS) is an eukaryotic cis prenyltransferase (cis-PT) that catalyzes chain elongation of farnesyl diphosphate via multiple condensations with isopentenyl diphosphate to form dehydrodolichyl diphosphate, a precursor for the glycosyl carrier dolichylpyrophophate involved in N-linked glycosylation. 28167250 3 21 theme Dehydrodolichyl 425:439 arg1 DHDDS 463:467 DHDDS 463:467 DHDDS 463:467 Dehydrodolichyl diphosphate synthase (DHDDS) is an eukaryotic cis prenyltransferase (cis-PT) that catalyzes chain elongation of farnesyl diphosphate via multiple condensations with isopentenyl diphosphate to form dehydrodolichyl diphosphate, a precursor for the glycosyl carrier dolichylpyrophophate involved in N-linked glycosylation. 28167250 6 22 theme cis-PT 1227:1232 arg1 drugs 1243:1247 prokaryotic cis-PT specific drugs 1215:1247 prokaryotic cis-PT specific drugs 1215:1247 However, as eukaryotic cis-PT were not thoroughly characterized structurally and functionally, rational design of prokaryotic cis-PT specific drugs is currently impossible. 28167250 3 23 theme diphosphate 441:451 arg1 synthase 453:460 Dehydrodolichyl diphosphate synthase 425:460 Dehydrodolichyl diphosphate synthase (DHDDS) 425:468 Dehydrodolichyl diphosphate synthase (DHDDS) is an eukaryotic cis prenyltransferase (cis-PT) that catalyzes chain elongation of farnesyl diphosphate via multiple condensations with isopentenyl diphosphate to form dehydrodolichyl diphosphate, a precursor for the glycosyl carrier dolichylpyrophophate involved in N-linked glycosylation. 28167250 3 23 theme diphosphate 441:451 arg1 prenyltransferase 491:507 an eukaryotic cis prenyltransferase 473:507 an eukaryotic cis prenyltransferase (cis-PT) that catalyzes chain elongation of farnesyl diphosphate via multiple condensations with isopentenyl diphosphate to form dehydrodolichyl diphosphate, a precursor for the glycosyl carrier dolichylpyrophophate involved in N-linked glycosylation 473:758 Dehydrodolichyl diphosphate synthase (DHDDS) is an eukaryotic cis prenyltransferase (cis-PT) that catalyzes chain elongation of farnesyl diphosphate via multiple condensations with isopentenyl diphosphate to form dehydrodolichyl diphosphate, a precursor for the glycosyl carrier dolichylpyrophophate involved in N-linked glycosylation. 28167250 3 23 theme diphosphate 441:451 arg1 DHDDS 463:467 DHDDS 463:467 DHDDS 463:467 Dehydrodolichyl diphosphate synthase (DHDDS) is an eukaryotic cis prenyltransferase (cis-PT) that catalyzes chain elongation of farnesyl diphosphate via multiple condensations with isopentenyl diphosphate to form dehydrodolichyl diphosphate, a precursor for the glycosyl carrier dolichylpyrophophate involved in N-linked glycosylation. 28167250 4 24 theme exact 867:871 arg1 mechanism 883:891 the exact molecular mechanism 863:891 the exact molecular mechanism by which the mutations affect DHDDS function 863:936 Mutations in DHDDS were shown to result in retinitis pigmentosa, ultimately leading to blindness, but the exact molecular mechanism by which the mutations affect DHDDS function remains elusive. 28167250 3 25 theme diphosphate 562:572 arg1 elongation 539:548 chain elongation 533:548 chain elongation of farnesyl diphosphate 533:572 Dehydrodolichyl diphosphate synthase (DHDDS) is an eukaryotic cis prenyltransferase (cis-PT) that catalyzes chain elongation of farnesyl diphosphate via multiple condensations with isopentenyl diphosphate to form dehydrodolichyl diphosphate, a precursor for the glycosyl carrier dolichylpyrophophate involved in N-linked glycosylation. 28167250 3 26 link N-linked 737:744 arg1 glycosylation 746:758 N-linked glycosylation 737:758 N-linked glycosylation 737:758 Dehydrodolichyl diphosphate synthase (DHDDS) is an eukaryotic cis prenyltransferase (cis-PT) that catalyzes chain elongation of farnesyl diphosphate via multiple condensations with isopentenyl diphosphate to form dehydrodolichyl diphosphate, a precursor for the glycosyl carrier dolichylpyrophophate involved in N-linked glycosylation. 28167250 3 27 with condensations 587:599 arg1 diphosphate 618:628 isopentenyl diphosphate 606:628 isopentenyl diphosphate 606:628 Dehydrodolichyl diphosphate synthase (DHDDS) is an eukaryotic cis prenyltransferase (cis-PT) that catalyzes chain elongation of farnesyl diphosphate via multiple condensations with isopentenyl diphosphate to form dehydrodolichyl diphosphate, a precursor for the glycosyl carrier dolichylpyrophophate involved in N-linked glycosylation. 28167250 11 28 theme therapeutic 1910:1920 arg1 approaches 1922:1931 novel therapeutic approaches 1904:1931 novel therapeutic approaches 1904:1931 Future structural and functional studies of the recombinant DHDDS may shed light on the mechanisms underlying DHDDS-related retinitis pigmentosa and lead to novel therapeutic approaches. 28167250 8 29 theme substrate-dependent 1532:1550 arg1 activity 1552:1559 substrate-dependent activity 1532:1559 substrate-dependent activity 1532:1559 The purified protein forms a stable homodimer, similar to its bacterial homologs, and shows time- and substrate-dependent activity. 28167250 7 30 theme codon-optimized 1403:1417 arg1 construct 1419:1427 a codon-optimized construct 1401:1427 a codon-optimized construct 1401:1427 Here, we present a simple protocol for purification of functionally active human DHDDS under non-denaturating conditions using a codon-optimized construct. 28167250 9 31 theme protein 1632:1638 arg1 solubility 1640:1649 protein solubility 1632:1649 protein solubility 1632:1649 Purification of this protein requires the presence of a detergent for protein solubility. 28167250 5 32 theme wall 1020:1023 arg1 synthesis 1025:1033 bacterial wall synthesis 1010:1033 bacterial wall synthesis 1010:1033 In addition, bacterial cis-PT homologs are involved in bacterial wall synthesis and are therefore potential targets for new antibacterial agents. 28167250 0 33 theme dehydrodolychil 43:57 arg1 DHDDS 81:85 DHDDS 81:85 DHDDS 81:85 Purification and characterization of human dehydrodolychil diphosphate synthase (DHDDS) overexpressed in E. coli. 28167250 0 33 theme dehydrodolychil 43:57 arg1 synthase 71:78 human dehydrodolychil diphosphate synthase 37:78 human dehydrodolychil diphosphate synthase (DHDDS) 37:86 Purification and characterization of human dehydrodolychil diphosphate synthase (DHDDS) overexpressed in E. coli. 28167250 1 34 link -linked 136:142 arg1 glycosylation 144:156 Protein asparagine (N)-linked glycosylation 114:156 Protein asparagine (N)-linked glycosylation 114:156 Protein asparagine (N)-linked glycosylation is a post-translational modification that occurs in the endoplasmic reticulum; it plays an important role in protein folding, oligomerization, quality control, sorting, and transport. 28167250 1 34 link -linked 136:142 arg1 modification 182:193 a post-translational modification 161:193 a post-translational modification that occurs in the endoplasmic reticulum 161:234 Protein asparagine (N)-linked glycosylation is a post-translational modification that occurs in the endoplasmic reticulum; it plays an important role in protein folding, oligomerization, quality control, sorting, and transport. 28167250 1 35 theme endoplasmic 214:224 arg1 reticulum 226:234 the endoplasmic reticulum 210:234 the endoplasmic reticulum 210:234 Protein asparagine (N)-linked glycosylation is a post-translational modification that occurs in the endoplasmic reticulum; it plays an important role in protein folding, oligomerization, quality control, sorting, and transport. 28167250 2 36 theme glycosylation 368:380 arg1 disorders 355:363 disorders 355:363 disorders of glycosylation 355:380 Accordingly, disorders of glycosylation may affect practically every organ system. 28167250 2 37 theme organ 411:415 arg1 system 417:422 practically every organ system 393:422 practically every organ system 393:422 Accordingly, disorders of glycosylation may affect practically every organ system. 28167250 0 38 theme human 37:41 arg1 DHDDS 81:85 DHDDS 81:85 DHDDS 81:85 Purification and characterization of human dehydrodolychil diphosphate synthase (DHDDS) overexpressed in E. coli. 28167250 0 38 theme human 37:41 arg1 synthase 71:78 human dehydrodolychil diphosphate synthase 37:78 human dehydrodolychil diphosphate synthase (DHDDS) 37:86 Purification and characterization of human dehydrodolychil diphosphate synthase (DHDDS) overexpressed in E. coli. 28167250 1 39 theme quality 301:307 arg1 control 309:315 quality control 301:315 quality control 301:315 Protein asparagine (N)-linked glycosylation is a post-translational modification that occurs in the endoplasmic reticulum; it plays an important role in protein folding, oligomerization, quality control, sorting, and transport. 28167250 10 40 theme eukaryotic 1728:1737 arg1 cis-PT 1739:1744 other eukaryotic cis-PT 1722:1744 other eukaryotic cis-PT 1722:1744 The protocol described here may be utilized for the overexpression of other eukaryotic cis-PT. 28167250 11 41 theme Future 1747:1752 arg1 studies 1780:1786 Future structural and functional studies 1747:1786 Future structural and functional studies of the recombinant DHDDS 1747:1811 Future structural and functional studies of the recombinant DHDDS may shed light on the mechanisms underlying DHDDS-related retinitis pigmentosa and lead to novel therapeutic approaches. 28167250 5 42 theme new 1075:1077 arg1 agents 1093:1098 new antibacterial agents 1075:1098 new antibacterial agents 1075:1098 In addition, bacterial cis-PT homologs are involved in bacterial wall synthesis and are therefore potential targets for new antibacterial agents. 28167250 9 43 theme protein 1583:1589 arg1 Purification 1562:1573 Purification 1562:1573 Purification of this protein 1562:1589 Purification of this protein requires the presence of a detergent for protein solubility. 28167250 0 44 theme synthase 71:78 arg1 characterization 17:32 characterization 17:32 characterization 17:32 Purification and characterization of human dehydrodolychil diphosphate synthase (DHDDS) overexpressed in E. coli. 28167250 0 44 theme synthase 71:78 arg1 Purification 0:11 Purification 0:11 Purification 0:11 Purification and characterization of human dehydrodolychil diphosphate synthase (DHDDS) overexpressed in E. coli. 28167250 10 45 used utilized 1687:1694 arg2 protocol 1656:1663 The protocol 1652:1663 The protocol described here 1652:1678 The protocol described here may be utilized for the overexpression of other eukaryotic cis-PT. 28167250 11 46 theme DHDDS 1807:1811 arg1 studies 1780:1786 Future structural and functional studies 1747:1786 Future structural and functional studies of the recombinant DHDDS 1747:1811 Future structural and functional studies of the recombinant DHDDS may shed light on the mechanisms underlying DHDDS-related retinitis pigmentosa and lead to novel therapeutic approaches. 28167250 4 47 theme molecular 873:881 arg1 mechanism 883:891 the exact molecular mechanism 863:891 the exact molecular mechanism by which the mutations affect DHDDS function 863:936 Mutations in DHDDS were shown to result in retinitis pigmentosa, ultimately leading to blindness, but the exact molecular mechanism by which the mutations affect DHDDS function remains elusive. 28167250 8 48 theme stable 1459:1464 arg1 homodimer 1466:1474 a stable homodimer 1457:1474 a stable homodimer 1457:1474 The purified protein forms a stable homodimer, similar to its bacterial homologs, and shows time- and substrate-dependent activity. 28167250 7 49 theme DHDDS 1355:1359 arg1 purification 1313:1324 purification 1313:1324 purification of functionally active human DHDDS 1313:1359 Here, we present a simple protocol for purification of functionally active human DHDDS under non-denaturating conditions using a codon-optimized construct. 28167250 0 50 theme diphosphate 59:69 arg1 DHDDS 81:85 DHDDS 81:85 DHDDS 81:85 Purification and characterization of human dehydrodolychil diphosphate synthase (DHDDS) overexpressed in E. coli. 28167250 0 50 theme diphosphate 59:69 arg1 synthase 71:78 human dehydrodolychil diphosphate synthase 37:78 human dehydrodolychil diphosphate synthase (DHDDS) 37:86 Purification and characterization of human dehydrodolychil diphosphate synthase (DHDDS) overexpressed in E. coli. 28167250 3 51 theme isopentenyl 606:616 arg1 diphosphate 618:628 isopentenyl diphosphate 606:628 isopentenyl diphosphate 606:628 Dehydrodolichyl diphosphate synthase (DHDDS) is an eukaryotic cis prenyltransferase (cis-PT) that catalyzes chain elongation of farnesyl diphosphate via multiple condensations with isopentenyl diphosphate to form dehydrodolichyl diphosphate, a precursor for the glycosyl carrier dolichylpyrophophate involved in N-linked glycosylation. 28167250 6 52 theme rational 1196:1203 arg1 design 1205:1210 rational design 1196:1210 rational design of prokaryotic cis-PT specific drugs 1196:1247 However, as eukaryotic cis-PT were not thoroughly characterized structurally and functionally, rational design of prokaryotic cis-PT specific drugs is currently impossible. 28167250 11 53 theme recombinant 1795:1805 arg1 DHDDS 1807:1811 the recombinant DHDDS 1791:1811 the recombinant DHDDS 1791:1811 Future structural and functional studies of the recombinant DHDDS may shed light on the mechanisms underlying DHDDS-related retinitis pigmentosa and lead to novel therapeutic approaches. 28167250 3 54 theme eukaryotic 476:485 arg1 prenyltransferase 491:507 an eukaryotic cis prenyltransferase 473:507 an eukaryotic cis prenyltransferase (cis-PT) that catalyzes chain elongation of farnesyl diphosphate via multiple condensations with isopentenyl diphosphate to form dehydrodolichyl diphosphate, a precursor for the glycosyl carrier dolichylpyrophophate involved in N-linked glycosylation 473:758 Dehydrodolichyl diphosphate synthase (DHDDS) is an eukaryotic cis prenyltransferase (cis-PT) that catalyzes chain elongation of farnesyl diphosphate via multiple condensations with isopentenyl diphosphate to form dehydrodolichyl diphosphate, a precursor for the glycosyl carrier dolichylpyrophophate involved in N-linked glycosylation. 28167250 3 54 theme eukaryotic 476:485 arg1 synthase 453:460 Dehydrodolichyl diphosphate synthase 425:460 Dehydrodolichyl diphosphate synthase (DHDDS) 425:468 Dehydrodolichyl diphosphate synthase (DHDDS) is an eukaryotic cis prenyltransferase (cis-PT) that catalyzes chain elongation of farnesyl diphosphate via multiple condensations with isopentenyl diphosphate to form dehydrodolichyl diphosphate, a precursor for the glycosyl carrier dolichylpyrophophate involved in N-linked glycosylation. 28167250 3 54 theme eukaryotic 476:485 arg1 cis-PT 510:515 cis-PT 510:515 cis-PT 510:515 Dehydrodolichyl diphosphate synthase (DHDDS) is an eukaryotic cis prenyltransferase (cis-PT) that catalyzes chain elongation of farnesyl diphosphate via multiple condensations with isopentenyl diphosphate to form dehydrodolichyl diphosphate, a precursor for the glycosyl carrier dolichylpyrophophate involved in N-linked glycosylation. 28167250 6 55 theme prokaryotic 1215:1225 arg1 drugs 1243:1247 prokaryotic cis-PT specific drugs 1215:1247 prokaryotic cis-PT specific drugs 1215:1247 However, as eukaryotic cis-PT were not thoroughly characterized structurally and functionally, rational design of prokaryotic cis-PT specific drugs is currently impossible. 28167250 11 56 theme retinitis 1871:1879 arg1 pigmentosa 1881:1890 DHDDS-related retinitis pigmentosa 1857:1890 DHDDS-related retinitis pigmentosa 1857:1890 Future structural and functional studies of the recombinant DHDDS may shed light on the mechanisms underlying DHDDS-related retinitis pigmentosa and lead to novel therapeutic approaches. 28167250 3 57 theme glycosyl 687:694 arg1 dolichylpyrophophate 704:723 the glycosyl carrier dolichylpyrophophate 683:723 the glycosyl carrier dolichylpyrophophate involved in N-linked glycosylation 683:758 Dehydrodolichyl diphosphate synthase (DHDDS) is an eukaryotic cis prenyltransferase (cis-PT) that catalyzes chain elongation of farnesyl diphosphate via multiple condensations with isopentenyl diphosphate to form dehydrodolichyl diphosphate, a precursor for the glycosyl carrier dolichylpyrophophate involved in N-linked glycosylation. 28167250 6 58 theme eukaryotic 1113:1122 arg1 cis-PT 1124:1129 eukaryotic cis-PT 1113:1129 eukaryotic cis-PT 1113:1129 However, as eukaryotic cis-PT were not thoroughly characterized structurally and functionally, rational design of prokaryotic cis-PT specific drugs is currently impossible. 28167250 3 59 theme cis 487:489 arg1 prenyltransferase 491:507 an eukaryotic cis prenyltransferase 473:507 an eukaryotic cis prenyltransferase (cis-PT) that catalyzes chain elongation of farnesyl diphosphate via multiple condensations with isopentenyl diphosphate to form dehydrodolichyl diphosphate, a precursor for the glycosyl carrier dolichylpyrophophate involved in N-linked glycosylation 473:758 Dehydrodolichyl diphosphate synthase (DHDDS) is an eukaryotic cis prenyltransferase (cis-PT) that catalyzes chain elongation of farnesyl diphosphate via multiple condensations with isopentenyl diphosphate to form dehydrodolichyl diphosphate, a precursor for the glycosyl carrier dolichylpyrophophate involved in N-linked glycosylation. 28167250 3 59 theme cis 487:489 arg1 synthase 453:460 Dehydrodolichyl diphosphate synthase 425:460 Dehydrodolichyl diphosphate synthase (DHDDS) 425:468 Dehydrodolichyl diphosphate synthase (DHDDS) is an eukaryotic cis prenyltransferase (cis-PT) that catalyzes chain elongation of farnesyl diphosphate via multiple condensations with isopentenyl diphosphate to form dehydrodolichyl diphosphate, a precursor for the glycosyl carrier dolichylpyrophophate involved in N-linked glycosylation. 28167250 3 59 theme cis 487:489 arg1 cis-PT 510:515 cis-PT 510:515 cis-PT 510:515 Dehydrodolichyl diphosphate synthase (DHDDS) is an eukaryotic cis prenyltransferase (cis-PT) that catalyzes chain elongation of farnesyl diphosphate via multiple condensations with isopentenyl diphosphate to form dehydrodolichyl diphosphate, a precursor for the glycosyl carrier dolichylpyrophophate involved in N-linked glycosylation. 28167250 8 60 theme purified 1434:1441 arg1 protein 1443:1449 The purified protein 1430:1449 The purified protein 1430:1449 The purified protein forms a stable homodimer, similar to its bacterial homologs, and shows time- and substrate-dependent activity. 28167250 5 61 theme cis-PT 978:983 arg1 homologs 985:992 bacterial cis-PT homologs 968:992 bacterial cis-PT homologs 968:992 In addition, bacterial cis-PT homologs are involved in bacterial wall synthesis and are therefore potential targets for new antibacterial agents. 28167250 7 62 theme simple 1293:1298 arg1 protocol 1300:1307 a simple protocol 1291:1307 a simple protocol for purification of functionally active human DHDDS 1291:1359 Here, we present a simple protocol for purification of functionally active human DHDDS under non-denaturating conditions using a codon-optimized construct. 28167250 3 63 theme carrier 696:702 arg1 dolichylpyrophophate 704:723 the glycosyl carrier dolichylpyrophophate 683:723 the glycosyl carrier dolichylpyrophophate involved in N-linked glycosylation 683:758 Dehydrodolichyl diphosphate synthase (DHDDS) is an eukaryotic cis prenyltransferase (cis-PT) that catalyzes chain elongation of farnesyl diphosphate via multiple condensations with isopentenyl diphosphate to form dehydrodolichyl diphosphate, a precursor for the glycosyl carrier dolichylpyrophophate involved in N-linked glycosylation. 28167250 5 64 theme potential 1053:1061 arg1 targets 1063:1069 potential targets 1053:1069 potential targets for new antibacterial agents 1053:1098 In addition, bacterial cis-PT homologs are involved in bacterial wall synthesis and are therefore potential targets for new antibacterial agents. 28167250 1 65 theme -linked 136:142 arg1 glycosylation 144:156 Protein asparagine (N)-linked glycosylation 114:156 Protein asparagine (N)-linked glycosylation 114:156 Protein asparagine (N)-linked glycosylation is a post-translational modification that occurs in the endoplasmic reticulum; it plays an important role in protein folding, oligomerization, quality control, sorting, and transport. 28167250 1 65 theme -linked 136:142 arg1 modification 182:193 a post-translational modification 161:193 a post-translational modification that occurs in the endoplasmic reticulum 161:234 Protein asparagine (N)-linked glycosylation is a post-translational modification that occurs in the endoplasmic reticulum; it plays an important role in protein folding, oligomerization, quality control, sorting, and transport. 28167250 4 66 from Mutations 761:769 arg1 DHDDS 774:778 DHDDS 774:778 DHDDS 774:778 Mutations in DHDDS were shown to result in retinitis pigmentosa, ultimately leading to blindness, but the exact molecular mechanism by which the mutations affect DHDDS function remains elusive. 28167250 10 67 theme other 1722:1726 arg1 cis-PT 1739:1744 other eukaryotic cis-PT 1722:1744 other eukaryotic cis-PT 1722:1744 The protocol described here may be utilized for the overexpression of other eukaryotic cis-PT. 28167250 11 68 theme structural 1754:1763 arg1 studies 1780:1786 Future structural and functional studies 1747:1786 Future structural and functional studies of the recombinant DHDDS 1747:1811 Future structural and functional studies of the recombinant DHDDS may shed light on the mechanisms underlying DHDDS-related retinitis pigmentosa and lead to novel therapeutic approaches. 28167250 3 69 theme dehydrodolichyl 638:652 arg1 diphosphate 654:664 dehydrodolichyl diphosphate 638:664 dehydrodolichyl diphosphate 638:664 Dehydrodolichyl diphosphate synthase (DHDDS) is an eukaryotic cis prenyltransferase (cis-PT) that catalyzes chain elongation of farnesyl diphosphate via multiple condensations with isopentenyl diphosphate to form dehydrodolichyl diphosphate, a precursor for the glycosyl carrier dolichylpyrophophate involved in N-linked glycosylation. 28167250 3 69 theme dehydrodolichyl 638:652 arg1 precursor 669:677 a precursor 667:677 a precursor for the glycosyl carrier dolichylpyrophophate involved in N-linked glycosylation 667:758 Dehydrodolichyl diphosphate synthase (DHDDS) is an eukaryotic cis prenyltransferase (cis-PT) that catalyzes chain elongation of farnesyl diphosphate via multiple condensations with isopentenyl diphosphate to form dehydrodolichyl diphosphate, a precursor for the glycosyl carrier dolichylpyrophophate involved in N-linked glycosylation. 28167250 7 70 theme active 1342:1347 arg1 DHDDS 1355:1359 functionally active human DHDDS 1329:1359 functionally active human DHDDS 1329:1359 Here, we present a simple protocol for purification of functionally active human DHDDS under non-denaturating conditions using a codon-optimized construct. 28167250 9 71 theme detergent 1618:1626 arg1 presence 1604:1611 the presence 1600:1611 the presence of a detergent for protein solubility 1600:1649 Purification of this protein requires the presence of a detergent for protein solubility. 28167250 11 72 theme DHDDS-related 1857:1869 arg1 pigmentosa 1881:1890 DHDDS-related retinitis pigmentosa 1857:1890 DHDDS-related retinitis pigmentosa 1857:1890 Future structural and functional studies of the recombinant DHDDS may shed light on the mechanisms underlying DHDDS-related retinitis pigmentosa and lead to novel therapeutic approaches. 27318275 10 0 theme mouse 2256:2260 arg1 macrophages 2262:2272 lipopolysaccharide (LPS)-stimulated mouse macrophages 2220:2272 lipopolysaccharide (LPS)-stimulated mouse macrophages 2220:2272 Furthermore, the in vitro anti-inflammatory potential of A. judaica oil was evaluated by measuring nitric oxide (NO) production using lipopolysaccharide (LPS)-stimulated mouse macrophages. 27318275 1 1 theme Arabia 344:349 arg1 borders 351:357 the Jordan-Saudi Arabia borders 327:357 the Jordan-Saudi Arabia borders 327:357 ETHNOPHARMACOLOGIC RELEVANCE Artemisia judaica L. (Arabic name: Beithran), is a medicinal and aromatic plant growing in the valley bottoms of desert areas, particularly in the southern desert of Jordan nearest to the Jordan-Saudi Arabia borders and in Wadi Araba in the Southern Badia. 27318275 11 2 theme constituents 2344:2355 arg1 % 2362:2362 68.7% 2358:2362 68.7% 2358:2362 RESULTS Oxygen containing monoterpenes are a representative group of constituents (68.7%) with piperitone (30.4%), camphor (16.1%) and ethyl cinnamate (11.0%) as main compounds. 27318275 11 2 theme constituents 2344:2355 arg1 group 2335:2339 a representative group 2318:2339 a representative group of constituents (68.7%) with piperitone (30.4%), camphor (16.1%) and ethyl cinnamate (11.0%) as main compounds 2318:2450 RESULTS Oxygen containing monoterpenes are a representative group of constituents (68.7%) with piperitone (30.4%), camphor (16.1%) and ethyl cinnamate (11.0%) as main compounds. 27318275 11 2 theme constituents 2344:2355 arg1 monoterpenes 2301:2312 RESULTS Oxygen containing monoterpenes 2275:2312 RESULTS Oxygen containing monoterpenes 2275:2312 RESULTS Oxygen containing monoterpenes are a representative group of constituents (68.7%) with piperitone (30.4%), camphor (16.1%) and ethyl cinnamate (11.0%) as main compounds. 27318275 11 2 theme constituents 2344:2355 arg1 constituents 2344:2355 constituents 2344:2355 constituents (68.7%) with piperitone (30.4%), camphor (16.1%) and ethyl cinnamate (11.0%) as main compounds 2344:2450 RESULTS Oxygen containing monoterpenes are a representative group of constituents (68.7%) with piperitone (30.4%), camphor (16.1%) and ethyl cinnamate (11.0%) as main compounds. 27318275 3 3 theme heart 611:615 arg1 diseases 617:624 heart diseases 611:624 heart diseases 611:624 Furthermore, it is used for the treatment of stomach ache, heart diseases, sexual weakness, diabetes, gastro-intestinal disorders and external wounding. 27318275 8 4 theme germ 1817:1820 arg1 assay 1838:1842 the germ tube inhibition assay 1813:1842 the germ tube inhibition assay 1813:1842 In order to deeply explore the mechanisms behind the anti-fungal effect of the essential oil, the germ tube inhibition assay and the biofilms formation assay were evaluated using Candida albicans. 27318275 6 5 theme oil 1412:1414 arg1 analysis 1379:1386 MATERIALS AND METHODS Chemical analysis 1348:1386 MATERIALS AND METHODS Chemical analysis of A. judaica essential oil isolated by hydrodistillation from aerial parts 1348:1462 MATERIALS AND METHODS Chemical analysis of A. judaica essential oil isolated by hydrodistillation from aerial parts was carried out by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). 27318275 11 6 with constituents 2344:2355 arg1 camphor 2390:2396 camphor 2390:2396 camphor (16.1%) 2390:2404 RESULTS Oxygen containing monoterpenes are a representative group of constituents (68.7%) with piperitone (30.4%), camphor (16.1%) and ethyl cinnamate (11.0%) as main compounds. 27318275 11 6 with constituents 2344:2355 arg1 cinnamate 2416:2424 ethyl cinnamate 2410:2424 ethyl cinnamate (11.0%) 2410:2432 RESULTS Oxygen containing monoterpenes are a representative group of constituents (68.7%) with piperitone (30.4%), camphor (16.1%) and ethyl cinnamate (11.0%) as main compounds. 27318275 11 6 with constituents 2344:2355 arg1 piperitone 2370:2379 piperitone 2370:2379 piperitone (30.4%) 2370:2387 RESULTS Oxygen containing monoterpenes are a representative group of constituents (68.7%) with piperitone (30.4%), camphor (16.1%) and ethyl cinnamate (11.0%) as main compounds. 27318275 11 6 with constituents 2344:2355 arg1 % 2403:2403 16.1% 2399:2403 16.1% 2399:2403 RESULTS Oxygen containing monoterpenes are a representative group of constituents (68.7%) with piperitone (30.4%), camphor (16.1%) and ethyl cinnamate (11.0%) as main compounds. 27318275 11 6 with constituents 2344:2355 arg1 % 2431:2431 11.0% 2427:2431 11.0% 2427:2431 RESULTS Oxygen containing monoterpenes are a representative group of constituents (68.7%) with piperitone (30.4%), camphor (16.1%) and ethyl cinnamate (11.0%) as main compounds. 27318275 11 6 with constituents 2344:2355 arg1 % 2386:2386 30.4% 2382:2386 30.4% 2382:2386 RESULTS Oxygen containing monoterpenes are a representative group of constituents (68.7%) with piperitone (30.4%), camphor (16.1%) and ethyl cinnamate (11.0%) as main compounds. 27318275 3 7 theme diabetes 644:651 arg1 treatment 584:592 the treatment 580:592 the treatment of stomach ache, heart diseases, sexual weakness, diabetes, gastro-intestinal disorders and external wounding 580:702 Furthermore, it is used for the treatment of stomach ache, heart diseases, sexual weakness, diabetes, gastro-intestinal disorders and external wounding. 27318275 8 8 theme inhibition 1827:1836 arg1 assay 1838:1842 the germ tube inhibition assay 1813:1842 the germ tube inhibition assay 1813:1842 In order to deeply explore the mechanisms behind the anti-fungal effect of the essential oil, the germ tube inhibition assay and the biofilms formation assay were evaluated using Candida albicans. 27318275 13 9 theme inhibitory 2603:2612 arg1 effect 2614:2619 an important inhibitory effect 2590:2619 an important inhibitory effect on germ tube formation in C. albicans 2590:2657 The oil revealed an important inhibitory effect on germ tube formation in C. albicans with 80% inhibition of filamentation at a concentration of 0.16µL/mL. 27318275 16 10 from Jordan 3133:3138 arg1 oil 3124:3126 A. judaica essential oil 3103:3126 A. judaica essential oil from Jordan 3103:3138 CONCLUSIONS The present study revealed that A. judaica essential oil from Jordan significantly inhibited germ tube formation and disrupted preformed biofilms of C. albicans, emphasizing the therapeutic potential for the treatment of disseminated candidiasis. 27318275 3 11 theme weakness 634:641 arg1 treatment 584:592 the treatment 580:592 the treatment of stomach ache, heart diseases, sexual weakness, diabetes, gastro-intestinal disorders and external wounding 580:702 Furthermore, it is used for the treatment of stomach ache, heart diseases, sexual weakness, diabetes, gastro-intestinal disorders and external wounding. 27318275 17 12 theme safe 3332:3335 arg1 concentrations 3337:3350 safe concentrations 3332:3350 safe concentrations of this essential oil 3332:3372 Additionally, safe concentrations of this essential oil significantly inhibited NO production elicited by LPS in macrophages, highlighting its potential anti-inflammatory activity. 27318275 6 13 theme A. 1391:1392 arg1 oil 1412:1414 A. judaica essential oil 1391:1414 A. judaica essential oil isolated by hydrodistillation from aerial parts 1391:1462 MATERIALS AND METHODS Chemical analysis of A. judaica essential oil isolated by hydrodistillation from aerial parts was carried out by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). 27318275 18 14 contain bears 3519:3523 arg1 judaica 3511:3517 A. judaica 3508:3517 A. judaica 3508:3517 Overall, A. judaica bears promising therapeutic potential for further drug development. 27318275 18 14 contain bears 3519:3523 arg2 potential 3547:3555 promising therapeutic potential 3525:3555 promising therapeutic potential for further drug development 3525:3584 Overall, A. judaica bears promising therapeutic potential for further drug development. 27318275 5 15 dep A. 1078:1079 arg1 judaica 1081:1087 judaica 1081:1087 judaica 1081:1087 AIM OF THE STUDY Considering the traditional medicinal uses and the lack of scientific studies addressing the cellular and molecular mechanisms behind A. judaica claimed activities, the present study was designed to validate some of the traditional uses ascribed to this species, specifically the antifungal and anti-inflammatory activities of A. judaica essential oil at doses devoid of cytotoxicity to mammalian cells. 27318275 8 16 theme biofilms 1852:1859 arg1 assay 1871:1875 the biofilms formation assay 1848:1875 the biofilms formation assay 1848:1875 In order to deeply explore the mechanisms behind the anti-fungal effect of the essential oil, the germ tube inhibition assay and the biofilms formation assay were evaluated using Candida albicans. 27318275 4 17 theme fungal 859:864 arg1 infections 866:875 fungal infections 859:875 fungal infections 859:875 Additionally, other folk medicines of the Arabic region commonly use this aromatic plant for the treatment of inflammatory-related diseases, for instance fungal infections, diabetes, atherosclerosis, cancer and arthritis. 27318275 11 18 theme Oxygen 2283:2288 arg1 group 2335:2339 a representative group 2318:2339 a representative group of constituents (68.7%) with piperitone (30.4%), camphor (16.1%) and ethyl cinnamate (11.0%) as main compounds 2318:2450 RESULTS Oxygen containing monoterpenes are a representative group of constituents (68.7%) with piperitone (30.4%), camphor (16.1%) and ethyl cinnamate (11.0%) as main compounds. 27318275 11 18 theme Oxygen 2283:2288 arg1 monoterpenes 2301:2312 RESULTS Oxygen containing monoterpenes 2275:2312 RESULTS Oxygen containing monoterpenes 2275:2312 RESULTS Oxygen containing monoterpenes are a representative group of constituents (68.7%) with piperitone (30.4%), camphor (16.1%) and ethyl cinnamate (11.0%) as main compounds. 27318275 11 18 theme Oxygen 2283:2288 arg1 constituents 2344:2355 constituents 2344:2355 constituents (68.7%) with piperitone (30.4%), camphor (16.1%) and ethyl cinnamate (11.0%) as main compounds 2344:2450 RESULTS Oxygen containing monoterpenes are a representative group of constituents (68.7%) with piperitone (30.4%), camphor (16.1%) and ethyl cinnamate (11.0%) as main compounds. 27318275 3 19 theme gastro-intestinal 654:670 arg1 disorders 672:680 gastro-intestinal disorders 654:680 gastro-intestinal disorders 654:680 Furthermore, it is used for the treatment of stomach ache, heart diseases, sexual weakness, diabetes, gastro-intestinal disorders and external wounding. 27318275 7 20 theme minimal 1582:1588 arg1 concentrations 1601:1614 minimal inhibitory concentrations 1582:1614 minimal inhibitory concentrations 1582:1614 The antifungal activity (minimal inhibitory concentrations and minimal lethal concentrations) was evaluated against yeasts, dermatophyte and Aspergillus strains. 27318275 15 21 theme essential 2856:2864 arg1 oil 2866:2868 the essential oil 2852:2868 the essential oil 2852:2868 Furthermore, the essential oil significantly inhibited NO production evoked by LPS on macrophages at concentrations with very low toxicity (0.32µL/mL) or without toxicity (0.16µL/mL) to both macrophages and hepatocytes. 27318275 5 22 theme studies 1014:1020 arg1 lack 995:998 the lack 991:998 the lack of scientific studies addressing the cellular and molecular mechanisms behind A. judaica claimed activities 991:1106 AIM OF THE STUDY Considering the traditional medicinal uses and the lack of scientific studies addressing the cellular and molecular mechanisms behind A. judaica claimed activities, the present study was designed to validate some of the traditional uses ascribed to this species, specifically the antifungal and anti-inflammatory activities of A. judaica essential oil at doses devoid of cytotoxicity to mammalian cells. 27318275 1 23 theme medicinal 194:202 arg1 plant 217:221 a medicinal and aromatic plant 192:221 a medicinal and aromatic plant growing in the valley bottoms of desert areas, particularly in the southern desert of Jordan nearest to the Jordan-Saudi Arabia borders and in Wadi Araba in the Southern Badia 192:397 ETHNOPHARMACOLOGIC RELEVANCE Artemisia judaica L. (Arabic name: Beithran), is a medicinal and aromatic plant growing in the valley bottoms of desert areas, particularly in the southern desert of Jordan nearest to the Jordan-Saudi Arabia borders and in Wadi Araba in the Southern Badia. 27318275 1 23 theme medicinal 194:202 arg1 RELEVANCE 133:141 ETHNOPHARMACOLOGIC RELEVANCE 114:141 ETHNOPHARMACOLOGIC RELEVANCE Artemisia judaica L. 114:162 ETHNOPHARMACOLOGIC RELEVANCE Artemisia judaica L. (Arabic name: Beithran), is a medicinal and aromatic plant growing in the valley bottoms of desert areas, particularly in the southern desert of Jordan nearest to the Jordan-Saudi Arabia borders and in Wadi Araba in the Southern Badia. 27318275 4 24 theme diseases 836:843 arg1 treatment 802:810 the treatment 798:810 the treatment of inflammatory-related diseases 798:843 Additionally, other folk medicines of the Arabic region commonly use this aromatic plant for the treatment of inflammatory-related diseases, for instance fungal infections, diabetes, atherosclerosis, cancer and arthritis. 27318275 5 25 dep traditional 1164:1174 arg1 uses 1176:1179 uses 1176:1179 uses 1176:1179 AIM OF THE STUDY Considering the traditional medicinal uses and the lack of scientific studies addressing the cellular and molecular mechanisms behind A. judaica claimed activities, the present study was designed to validate some of the traditional uses ascribed to this species, specifically the antifungal and anti-inflammatory activities of A. judaica essential oil at doses devoid of cytotoxicity to mammalian cells. 27318275 10 26 theme oil 2154:2156 arg1 potential 2130:2138 the in vitro anti-inflammatory potential 2099:2138 the in vitro anti-inflammatory potential of A. judaica oil 2099:2156 Furthermore, the in vitro anti-inflammatory potential of A. judaica oil was evaluated by measuring nitric oxide (NO) production using lipopolysaccharide (LPS)-stimulated mouse macrophages. 27318275 3 27 theme wounding 695:702 arg1 treatment 584:592 the treatment 580:592 the treatment of stomach ache, heart diseases, sexual weakness, diabetes, gastro-intestinal disorders and external wounding 580:702 Furthermore, it is used for the treatment of stomach ache, heart diseases, sexual weakness, diabetes, gastro-intestinal disorders and external wounding. 27318275 8 28 theme Candida 1898:1904 arg1 albicans 1906:1913 Candida albicans 1898:1913 Candida albicans 1898:1913 In order to deeply explore the mechanisms behind the anti-fungal effect of the essential oil, the germ tube inhibition assay and the biofilms formation assay were evaluated using Candida albicans. 27318275 2 29 theme Badia 515:519 arg1 region 521:526 the North Badia region 505:526 the North Badia region of Jordan 505:536 In Jordan, A. judaica is widely used in traditional medicine being recommended by aboriginal Bedouins in the North Badia region of Jordan as calmative. 27318275 9 30 theme viability 1939:1947 arg1 assessment 1920:1929 The assessment 1916:1929 The assessment of cell viability 1916:1947 The assessment of cell viability was accomplished using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in both hepatocytes and macrophages. 27318275 16 31 dep CONCLUSIONS 3059:3069 arg1 revealed 3089:3096 revealed 3089:3096 revealed that A. judaica essential oil from Jordan significantly inhibited germ tube formation and disrupted preformed biofilms of C. albicans, emphasizing the therapeutic potential for the treatment of disseminated candidiasis 3089:3315 CONCLUSIONS The present study revealed that A. judaica essential oil from Jordan significantly inhibited germ tube formation and disrupted preformed biofilms of C. albicans, emphasizing the therapeutic potential for the treatment of disseminated candidiasis. 27318275 10 32 theme A. 2143:2144 arg1 oil 2154:2156 A. judaica oil 2143:2156 A. judaica oil 2143:2156 Furthermore, the in vitro anti-inflammatory potential of A. judaica oil was evaluated by measuring nitric oxide (NO) production using lipopolysaccharide (LPS)-stimulated mouse macrophages. 27318275 6 33 theme chromatography-mass 1515:1533 arg1 GC-MS 1549:1553 GC-MS 1549:1553 GC-MS 1549:1553 MATERIALS AND METHODS Chemical analysis of A. judaica essential oil isolated by hydrodistillation from aerial parts was carried out by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). 27318275 6 33 theme chromatography-mass 1515:1533 arg1 spectrometry 1535:1546 gas chromatography-mass spectrometry 1511:1546 gas chromatography-mass spectrometry (GC-MS) 1511:1554 MATERIALS AND METHODS Chemical analysis of A. judaica essential oil isolated by hydrodistillation from aerial parts was carried out by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). 27318275 1 34 theme judaica 153:159 arg1 L 161:161 Artemisia judaica L 143:161 ETHNOPHARMACOLOGIC RELEVANCE Artemisia judaica L. 114:162 ETHNOPHARMACOLOGIC RELEVANCE Artemisia judaica L. (Arabic name: Beithran), is a medicinal and aromatic plant growing in the valley bottoms of desert areas, particularly in the southern desert of Jordan nearest to the Jordan-Saudi Arabia borders and in Wadi Araba in the Southern Badia. 27318275 7 35 theme Aspergillus 1698:1708 arg1 strains 1710:1716 Aspergillus strains 1698:1716 Aspergillus strains 1698:1716 The antifungal activity (minimal inhibitory concentrations and minimal lethal concentrations) was evaluated against yeasts, dermatophyte and Aspergillus strains. 27318275 2 36 theme traditional 440:450 arg1 medicine 452:459 traditional medicine 440:459 traditional medicine being recommended by aboriginal Bedouins in the North Badia region of Jordan as calmative 440:549 In Jordan, A. judaica is widely used in traditional medicine being recommended by aboriginal Bedouins in the North Badia region of Jordan as calmative. 27318275 0 37 from desert 96:101 arg1 oil 78:80 essential oil 68:80 essential oil from southern desert of Jordan 68:111 Chemical composition and biological activities of Artemisia judaica essential oil from southern desert of Jordan. 27318275 0 38 theme essential 68:76 arg1 oil 78:80 essential oil 68:80 essential oil from southern desert of Jordan 68:111 Chemical composition and biological activities of Artemisia judaica essential oil from southern desert of Jordan. 27318275 12 39 theme MIC 2549:2551 arg1 value 2553:2557 a MIC value 2547:2557 a MIC value of 0.16µL/mL 2547:2570 The highest antifungal activity of the oil was observed against Cryptococcus neoformans, with a MIC value of 0.16µL/mL. 27318275 1 40 theme Jordan 309:314 arg1 desert 299:304 the southern desert 286:304 the southern desert of Jordan nearest to the Jordan-Saudi Arabia borders 286:357 ETHNOPHARMACOLOGIC RELEVANCE Artemisia judaica L. (Arabic name: Beithran), is a medicinal and aromatic plant growing in the valley bottoms of desert areas, particularly in the southern desert of Jordan nearest to the Jordan-Saudi Arabia borders and in Wadi Araba in the Southern Badia. 27318275 1 41 theme Arabic 165:170 arg1 name 172:175 Arabic name 165:175 Arabic name: Beithran 165:185 ETHNOPHARMACOLOGIC RELEVANCE Artemisia judaica L. (Arabic name: Beithran), is a medicinal and aromatic plant growing in the valley bottoms of desert areas, particularly in the southern desert of Jordan nearest to the Jordan-Saudi Arabia borders and in Wadi Araba in the Southern Badia. 27318275 11 42 theme ethyl 2410:2414 arg1 cinnamate 2416:2424 ethyl cinnamate 2410:2424 ethyl cinnamate (11.0%) 2410:2432 RESULTS Oxygen containing monoterpenes are a representative group of constituents (68.7%) with piperitone (30.4%), camphor (16.1%) and ethyl cinnamate (11.0%) as main compounds. 27318275 11 42 theme ethyl 2410:2414 arg1 % 2431:2431 11.0% 2427:2431 11.0% 2427:2431 RESULTS Oxygen containing monoterpenes are a representative group of constituents (68.7%) with piperitone (30.4%), camphor (16.1%) and ethyl cinnamate (11.0%) as main compounds. 27318275 13 43 theme C. 2647:2648 arg1 albicans 2650:2657 C. albicans 2647:2657 C. albicans 2647:2657 The oil revealed an important inhibitory effect on germ tube formation in C. albicans with 80% inhibition of filamentation at a concentration of 0.16µL/mL. 27318275 16 44 theme tube 3169:3172 arg1 formation 3174:3182 germ tube formation 3164:3182 germ tube formation 3164:3182 CONCLUSIONS The present study revealed that A. judaica essential oil from Jordan significantly inhibited germ tube formation and disrupted preformed biofilms of C. albicans, emphasizing the therapeutic potential for the treatment of disseminated candidiasis. 27318275 16 45 theme A. 3103:3104 arg1 oil 3124:3126 A. judaica essential oil 3103:3126 A. judaica essential oil from Jordan 3103:3138 CONCLUSIONS The present study revealed that A. judaica essential oil from Jordan significantly inhibited germ tube formation and disrupted preformed biofilms of C. albicans, emphasizing the therapeutic potential for the treatment of disseminated candidiasis. 27318275 19 46 theme judaica 3660:3666 arg1 traditional 3637:3647 traditional 3637:3647 traditional 3637:3647 Importantly, this work also validates some of the traditional uses of A. judaica. 27318275 16 47 theme C. 3220:3221 arg1 albicans 3223:3230 C. albicans 3220:3230 C. albicans 3220:3230 CONCLUSIONS The present study revealed that A. judaica essential oil from Jordan significantly inhibited germ tube formation and disrupted preformed biofilms of C. albicans, emphasizing the therapeutic potential for the treatment of disseminated candidiasis. 27318275 10 48 theme oxide 2192:2196 arg1 production 2203:2212 nitric oxide (NO) production 2185:2212 nitric oxide (NO) production 2185:2212 Furthermore, the in vitro anti-inflammatory potential of A. judaica oil was evaluated by measuring nitric oxide (NO) production using lipopolysaccharide (LPS)-stimulated mouse macrophages. 27318275 5 49 theme essential 1282:1290 arg1 oil 1292:1294 A. judaica essential oil 1271:1294 A. judaica essential oil at doses devoid of cytotoxicity to mammalian cells 1271:1345 AIM OF THE STUDY Considering the traditional medicinal uses and the lack of scientific studies addressing the cellular and molecular mechanisms behind A. judaica claimed activities, the present study was designed to validate some of the traditional uses ascribed to this species, specifically the antifungal and anti-inflammatory activities of A. judaica essential oil at doses devoid of cytotoxicity to mammalian cells. 27318275 0 50 theme Jordan 106:111 arg1 desert 96:101 southern desert 87:101 southern desert of Jordan 87:111 Chemical composition and biological activities of Artemisia judaica essential oil from southern desert of Jordan. 27318275 8 51 theme oil 1808:1810 arg1 effect 1784:1789 the anti-fungal effect 1768:1789 the anti-fungal effect of the essential oil 1768:1810 In order to deeply explore the mechanisms behind the anti-fungal effect of the essential oil, the germ tube inhibition assay and the biofilms formation assay were evaluated using Candida albicans. 27318275 9 52 theme bromide 2029:2035 arg1 assay 2043:2047 the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay 1972:2047 the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in both hepatocytes and macrophages 1972:2083 The assessment of cell viability was accomplished using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in both hepatocytes and macrophages. 27318275 0 53 theme Chemical 0:7 arg1 composition 9:19 Chemical composition 0:19 Chemical composition 0:19 Chemical composition and biological activities of Artemisia judaica essential oil from southern desert of Jordan. 27318275 5 54 theme present 1113:1119 arg1 study 1121:1125 the present study 1109:1125 the present study 1109:1125 AIM OF THE STUDY Considering the traditional medicinal uses and the lack of scientific studies addressing the cellular and molecular mechanisms behind A. judaica claimed activities, the present study was designed to validate some of the traditional uses ascribed to this species, specifically the antifungal and anti-inflammatory activities of A. judaica essential oil at doses devoid of cytotoxicity to mammalian cells. 27318275 13 55 theme filamentation 2682:2694 arg1 inhibition 2668:2677 80% inhibition 2664:2677 80% inhibition of filamentation 2664:2694 The oil revealed an important inhibitory effect on germ tube formation in C. albicans with 80% inhibition of filamentation at a concentration of 0.16µL/mL. 27318275 7 56 theme lethal 1628:1633 arg1 concentrations 1635:1648 minimal lethal concentrations 1620:1648 minimal lethal concentrations 1620:1648 The antifungal activity (minimal inhibitory concentrations and minimal lethal concentrations) was evaluated against yeasts, dermatophyte and Aspergillus strains. 27318275 3 57 used used 571:574 arg2 it 565:566 it 565:566 it 565:566 Furthermore, it is used for the treatment of stomach ache, heart diseases, sexual weakness, diabetes, gastro-intestinal disorders and external wounding. 27318275 19 58 dep traditional 3637:3647 arg1 uses 3649:3652 uses 3649:3652 uses 3649:3652 Importantly, this work also validates some of the traditional uses of A. judaica. 27318275 18 59 theme drug 3569:3572 arg1 development 3574:3584 further drug development 3561:3584 further drug development 3561:3584 Overall, A. judaica bears promising therapeutic potential for further drug development. 27318275 16 60 theme germ 3164:3167 arg1 formation 3174:3182 germ tube formation 3164:3182 germ tube formation 3164:3182 CONCLUSIONS The present study revealed that A. judaica essential oil from Jordan significantly inhibited germ tube formation and disrupted preformed biofilms of C. albicans, emphasizing the therapeutic potential for the treatment of disseminated candidiasis. 27318275 1 61 theme areas 263:267 arg1 bottoms 245:251 the valley bottoms 234:251 the valley bottoms of desert areas 234:267 ETHNOPHARMACOLOGIC RELEVANCE Artemisia judaica L. (Arabic name: Beithran), is a medicinal and aromatic plant growing in the valley bottoms of desert areas, particularly in the southern desert of Jordan nearest to the Jordan-Saudi Arabia borders and in Wadi Araba in the Southern Badia. 27318275 4 62 theme Arabic 747:752 arg1 region 754:759 the Arabic region 743:759 the Arabic region 743:759 Additionally, other folk medicines of the Arabic region commonly use this aromatic plant for the treatment of inflammatory-related diseases, for instance fungal infections, diabetes, atherosclerosis, cancer and arthritis. 27318275 5 63 theme A. 1271:1272 arg1 oil 1292:1294 A. judaica essential oil 1271:1294 A. judaica essential oil at doses devoid of cytotoxicity to mammalian cells 1271:1345 AIM OF THE STUDY Considering the traditional medicinal uses and the lack of scientific studies addressing the cellular and molecular mechanisms behind A. judaica claimed activities, the present study was designed to validate some of the traditional uses ascribed to this species, specifically the antifungal and anti-inflammatory activities of A. judaica essential oil at doses devoid of cytotoxicity to mammalian cells. 27318275 6 64 theme METHODS 1362:1368 arg1 analysis 1379:1386 MATERIALS AND METHODS Chemical analysis 1348:1386 MATERIALS AND METHODS Chemical analysis of A. judaica essential oil isolated by hydrodistillation from aerial parts 1348:1462 MATERIALS AND METHODS Chemical analysis of A. judaica essential oil isolated by hydrodistillation from aerial parts was carried out by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). 27318275 5 65 theme claimed 1089:1095 arg1 activities 1097:1106 A. judaica claimed activities 1078:1106 A. judaica claimed activities 1078:1106 AIM OF THE STUDY Considering the traditional medicinal uses and the lack of scientific studies addressing the cellular and molecular mechanisms behind A. judaica claimed activities, the present study was designed to validate some of the traditional uses ascribed to this species, specifically the antifungal and anti-inflammatory activities of A. judaica essential oil at doses devoid of cytotoxicity to mammalian cells. 27318275 1 66 dep name 172:175 arg1 Beithran 178:185 Beithran 178:185 Beithran 178:185 ETHNOPHARMACOLOGIC RELEVANCE Artemisia judaica L. (Arabic name: Beithran), is a medicinal and aromatic plant growing in the valley bottoms of desert areas, particularly in the southern desert of Jordan nearest to the Jordan-Saudi Arabia borders and in Wadi Araba in the Southern Badia. 27318275 5 67 theme mammalian 1331:1339 arg1 cells 1341:1345 mammalian cells 1331:1345 mammalian cells 1331:1345 AIM OF THE STUDY Considering the traditional medicinal uses and the lack of scientific studies addressing the cellular and molecular mechanisms behind A. judaica claimed activities, the present study was designed to validate some of the traditional uses ascribed to this species, specifically the antifungal and anti-inflammatory activities of A. judaica essential oil at doses devoid of cytotoxicity to mammalian cells. 27318275 0 68 theme Artemisia 50:58 arg1 composition 9:19 Chemical composition 0:19 Chemical composition 0:19 Chemical composition and biological activities of Artemisia judaica essential oil from southern desert of Jordan. 27318275 0 68 theme Artemisia 50:58 arg1 activities 36:45 biological activities 25:45 biological activities 25:45 Chemical composition and biological activities of Artemisia judaica essential oil from southern desert of Jordan. 27318275 12 69 theme antifungal 2465:2474 arg1 activity 2476:2483 The highest antifungal activity 2453:2483 The highest antifungal activity of the oil 2453:2494 The highest antifungal activity of the oil was observed against Cryptococcus neoformans, with a MIC value of 0.16µL/mL. 27318275 17 70 theme potential 3461:3469 arg1 activity 3489:3496 its potential anti-inflammatory activity 3457:3496 its potential anti-inflammatory activity 3457:3496 Additionally, safe concentrations of this essential oil significantly inhibited NO production elicited by LPS in macrophages, highlighting its potential anti-inflammatory activity. 27318275 2 71 used used 432:435 arg2 judaica 414:420 A. judaica 411:420 A. judaica 411:420 In Jordan, A. judaica is widely used in traditional medicine being recommended by aboriginal Bedouins in the North Badia region of Jordan as calmative. 27318275 4 72 theme folk 725:728 arg1 medicines 730:738 other folk medicines 719:738 other folk medicines of the Arabic region 719:759 Additionally, other folk medicines of the Arabic region commonly use this aromatic plant for the treatment of inflammatory-related diseases, for instance fungal infections, diabetes, atherosclerosis, cancer and arthritis. 27318275 6 73 theme aerial 1451:1456 arg1 parts 1458:1462 aerial parts 1451:1462 aerial parts 1451:1462 MATERIALS AND METHODS Chemical analysis of A. judaica essential oil isolated by hydrodistillation from aerial parts was carried out by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). 27318275 6 74 dep A. 1391:1392 arg1 judaica 1394:1400 judaica 1394:1400 judaica 1394:1400 MATERIALS AND METHODS Chemical analysis of A. judaica essential oil isolated by hydrodistillation from aerial parts was carried out by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). 27318275 15 75 theme low 2965:2967 arg1 0.32µL/mL 2979:2987 0.32µL/mL 2979:2987 0.32µL/mL 2979:2987 Furthermore, the essential oil significantly inhibited NO production evoked by LPS on macrophages at concentrations with very low toxicity (0.32µL/mL) or without toxicity (0.16µL/mL) to both macrophages and hepatocytes. 27318275 15 75 theme low 2965:2967 arg1 toxicity 2969:2976 very low toxicity 2960:2976 very low toxicity (0.32µL/mL) 2960:2988 Furthermore, the essential oil significantly inhibited NO production evoked by LPS on macrophages at concentrations with very low toxicity (0.32µL/mL) or without toxicity (0.16µL/mL) to both macrophages and hepatocytes. 27318275 8 76 dep mechanisms 1750:1759 arg1 behind 1761:1766 behind 1761:1766 behind the anti-fungal effect of the essential oil 1761:1810 In order to deeply explore the mechanisms behind the anti-fungal effect of the essential oil, the germ tube inhibition assay and the biofilms formation assay were evaluated using Candida albicans. 27318275 16 77 theme candidiasis 3305:3315 arg1 treatment 3279:3287 the treatment 3275:3287 the treatment of disseminated candidiasis 3275:3315 CONCLUSIONS The present study revealed that A. judaica essential oil from Jordan significantly inhibited germ tube formation and disrupted preformed biofilms of C. albicans, emphasizing the therapeutic potential for the treatment of disseminated candidiasis. 27318275 3 78 theme stomach 597:603 arg1 ache 605:608 stomach ache 597:608 stomach ache 597:608 Furthermore, it is used for the treatment of stomach ache, heart diseases, sexual weakness, diabetes, gastro-intestinal disorders and external wounding. 27318275 5 79 theme devoid 1305:1310 arg1 doses 1299:1303 doses 1299:1303 doses devoid of cytotoxicity to mammalian cells 1299:1345 AIM OF THE STUDY Considering the traditional medicinal uses and the lack of scientific studies addressing the cellular and molecular mechanisms behind A. judaica claimed activities, the present study was designed to validate some of the traditional uses ascribed to this species, specifically the antifungal and anti-inflammatory activities of A. judaica essential oil at doses devoid of cytotoxicity to mammalian cells. 27318275 13 80 theme % 2666:2666 arg1 inhibition 2668:2677 80% inhibition 2664:2677 80% inhibition of filamentation 2664:2694 The oil revealed an important inhibitory effect on germ tube formation in C. albicans with 80% inhibition of filamentation at a concentration of 0.16µL/mL. 27318275 5 81 theme STUDY 938:942 arg1 AIM 927:929 AIM 927:929 AIM OF THE STUDY 927:942 AIM OF THE STUDY Considering the traditional medicinal uses and the lack of scientific studies addressing the cellular and molecular mechanisms behind A. judaica claimed activities, the present study was designed to validate some of the traditional uses ascribed to this species, specifically the antifungal and anti-inflammatory activities of A. judaica essential oil at doses devoid of cytotoxicity to mammalian cells. 27318275 10 82 dep in 2103:2104 arg1 vitro 2106:2110 vitro 2106:2110 vitro 2106:2110 Furthermore, the in vitro anti-inflammatory potential of A. judaica oil was evaluated by measuring nitric oxide (NO) production using lipopolysaccharide (LPS)-stimulated mouse macrophages. 27318275 18 83 theme promising 3525:3533 arg1 potential 3547:3555 promising therapeutic potential 3525:3555 promising therapeutic potential for further drug development 3525:3584 Overall, A. judaica bears promising therapeutic potential for further drug development. 27318275 3 84 theme sexual 627:632 arg1 weakness 634:641 sexual weakness 627:641 sexual weakness 627:641 Furthermore, it is used for the treatment of stomach ache, heart diseases, sexual weakness, diabetes, gastro-intestinal disorders and external wounding. 27318275 8 85 theme tube 1822:1825 arg1 assay 1838:1842 the germ tube inhibition assay 1813:1842 the germ tube inhibition assay 1813:1842 In order to deeply explore the mechanisms behind the anti-fungal effect of the essential oil, the germ tube inhibition assay and the biofilms formation assay were evaluated using Candida albicans. 27318275 5 86 theme cytotoxicity 1315:1326 arg1 devoid 1305:1310 devoid 1305:1310 devoid 1305:1310 AIM OF THE STUDY Considering the traditional medicinal uses and the lack of scientific studies addressing the cellular and molecular mechanisms behind A. judaica claimed activities, the present study was designed to validate some of the traditional uses ascribed to this species, specifically the antifungal and anti-inflammatory activities of A. judaica essential oil at doses devoid of cytotoxicity to mammalian cells. 27318275 10 87 theme -stimulated 2244:2254 arg1 macrophages 2262:2272 lipopolysaccharide (LPS)-stimulated mouse macrophages 2220:2272 lipopolysaccharide (LPS)-stimulated mouse macrophages 2220:2272 Furthermore, the in vitro anti-inflammatory potential of A. judaica oil was evaluated by measuring nitric oxide (NO) production using lipopolysaccharide (LPS)-stimulated mouse macrophages. 27318275 11 88 theme representative 2320:2333 arg1 % 2362:2362 68.7% 2358:2362 68.7% 2358:2362 RESULTS Oxygen containing monoterpenes are a representative group of constituents (68.7%) with piperitone (30.4%), camphor (16.1%) and ethyl cinnamate (11.0%) as main compounds. 27318275 11 88 theme representative 2320:2333 arg1 group 2335:2339 a representative group 2318:2339 a representative group of constituents (68.7%) with piperitone (30.4%), camphor (16.1%) and ethyl cinnamate (11.0%) as main compounds 2318:2450 RESULTS Oxygen containing monoterpenes are a representative group of constituents (68.7%) with piperitone (30.4%), camphor (16.1%) and ethyl cinnamate (11.0%) as main compounds. 27318275 11 88 theme representative 2320:2333 arg1 monoterpenes 2301:2312 RESULTS Oxygen containing monoterpenes 2275:2312 RESULTS Oxygen containing monoterpenes 2275:2312 RESULTS Oxygen containing monoterpenes are a representative group of constituents (68.7%) with piperitone (30.4%), camphor (16.1%) and ethyl cinnamate (11.0%) as main compounds. 27318275 11 88 theme representative 2320:2333 arg1 constituents 2344:2355 constituents 2344:2355 constituents (68.7%) with piperitone (30.4%), camphor (16.1%) and ethyl cinnamate (11.0%) as main compounds 2344:2450 RESULTS Oxygen containing monoterpenes are a representative group of constituents (68.7%) with piperitone (30.4%), camphor (16.1%) and ethyl cinnamate (11.0%) as main compounds. 27318275 3 89 theme diseases 617:624 arg1 treatment 584:592 the treatment 580:592 the treatment of stomach ache, heart diseases, sexual weakness, diabetes, gastro-intestinal disorders and external wounding 580:702 Furthermore, it is used for the treatment of stomach ache, heart diseases, sexual weakness, diabetes, gastro-intestinal disorders and external wounding. 27318275 15 90 with concentrations 2940:2953 arg1 0.32µL/mL 2979:2987 0.32µL/mL 2979:2987 0.32µL/mL 2979:2987 Furthermore, the essential oil significantly inhibited NO production evoked by LPS on macrophages at concentrations with very low toxicity (0.32µL/mL) or without toxicity (0.16µL/mL) to both macrophages and hepatocytes. 27318275 15 90 with concentrations 2940:2953 arg1 toxicity 2969:2976 very low toxicity 2960:2976 very low toxicity (0.32µL/mL) 2960:2988 Furthermore, the essential oil significantly inhibited NO production evoked by LPS on macrophages at concentrations with very low toxicity (0.32µL/mL) or without toxicity (0.16µL/mL) to both macrophages and hepatocytes. 27318275 6 91 theme essential 1402:1410 arg1 oil 1412:1414 A. judaica essential oil 1391:1414 A. judaica essential oil isolated by hydrodistillation from aerial parts 1391:1462 MATERIALS AND METHODS Chemical analysis of A. judaica essential oil isolated by hydrodistillation from aerial parts was carried out by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). 27318275 1 92 theme valley 238:243 arg1 bottoms 245:251 the valley bottoms 234:251 the valley bottoms of desert areas 234:267 ETHNOPHARMACOLOGIC RELEVANCE Artemisia judaica L. (Arabic name: Beithran), is a medicinal and aromatic plant growing in the valley bottoms of desert areas, particularly in the southern desert of Jordan nearest to the Jordan-Saudi Arabia borders and in Wadi Araba in the Southern Badia. 27318275 2 93 theme Jordan 531:536 arg1 region 521:526 the North Badia region 505:526 the North Badia region of Jordan 505:536 In Jordan, A. judaica is widely used in traditional medicine being recommended by aboriginal Bedouins in the North Badia region of Jordan as calmative. 27318275 10 94 theme in 2103:2104 arg1 potential 2130:2138 the in vitro anti-inflammatory potential 2099:2138 the in vitro anti-inflammatory potential of A. judaica oil 2099:2156 Furthermore, the in vitro anti-inflammatory potential of A. judaica oil was evaluated by measuring nitric oxide (NO) production using lipopolysaccharide (LPS)-stimulated mouse macrophages. 27318275 13 95 theme germ 2624:2627 arg1 formation 2634:2642 germ tube formation 2624:2642 germ tube formation 2624:2642 The oil revealed an important inhibitory effect on germ tube formation in C. albicans with 80% inhibition of filamentation at a concentration of 0.16µL/mL. 27318275 16 96 dep A. 3103:3104 arg1 judaica 3106:3112 judaica 3106:3112 judaica 3106:3112 CONCLUSIONS The present study revealed that A. judaica essential oil from Jordan significantly inhibited germ tube formation and disrupted preformed biofilms of C. albicans, emphasizing the therapeutic potential for the treatment of disseminated candidiasis. 27318275 16 96 dep A. 3103:3104 arg1 essential 3114:3122 essential 3114:3122 essential 3114:3122 CONCLUSIONS The present study revealed that A. judaica essential oil from Jordan significantly inhibited germ tube formation and disrupted preformed biofilms of C. albicans, emphasizing the therapeutic potential for the treatment of disseminated candidiasis. 27318275 6 97 theme MATERIALS 1348:1356 arg1 analysis 1379:1386 MATERIALS AND METHODS Chemical analysis 1348:1386 MATERIALS AND METHODS Chemical analysis of A. judaica essential oil isolated by hydrodistillation from aerial parts 1348:1462 MATERIALS AND METHODS Chemical analysis of A. judaica essential oil isolated by hydrodistillation from aerial parts was carried out by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). 27318275 5 98 dep medicinal 972:980 arg1 uses 982:985 uses 982:985 uses 982:985 AIM OF THE STUDY Considering the traditional medicinal uses and the lack of scientific studies addressing the cellular and molecular mechanisms behind A. judaica claimed activities, the present study was designed to validate some of the traditional uses ascribed to this species, specifically the antifungal and anti-inflammatory activities of A. judaica essential oil at doses devoid of cytotoxicity to mammalian cells. 27318275 8 99 theme formation 1861:1869 arg1 assay 1871:1875 the biofilms formation assay 1848:1875 the biofilms formation assay 1848:1875 In order to deeply explore the mechanisms behind the anti-fungal effect of the essential oil, the germ tube inhibition assay and the biofilms formation assay were evaluated using Candida albicans. 27318275 7 100 dep activity 1572:1579 arg1 concentrations 1635:1648 minimal lethal concentrations 1620:1648 minimal lethal concentrations 1620:1648 The antifungal activity (minimal inhibitory concentrations and minimal lethal concentrations) was evaluated against yeasts, dermatophyte and Aspergillus strains. 27318275 7 100 dep activity 1572:1579 arg1 concentrations 1601:1614 minimal inhibitory concentrations 1582:1614 minimal inhibitory concentrations 1582:1614 The antifungal activity (minimal inhibitory concentrations and minimal lethal concentrations) was evaluated against yeasts, dermatophyte and Aspergillus strains. 27318275 6 101 theme gas 1483:1485 arg1 chromatography 1487:1500 gas chromatography 1483:1500 gas chromatography (GC) 1483:1505 MATERIALS AND METHODS Chemical analysis of A. judaica essential oil isolated by hydrodistillation from aerial parts was carried out by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). 27318275 6 101 theme gas 1483:1485 arg1 GC 1503:1504 GC 1503:1504 GC 1503:1504 MATERIALS AND METHODS Chemical analysis of A. judaica essential oil isolated by hydrodistillation from aerial parts was carried out by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). 27318275 5 102 theme A. 1078:1079 arg1 activities 1097:1106 A. judaica claimed activities 1078:1106 A. judaica claimed activities 1078:1106 AIM OF THE STUDY Considering the traditional medicinal uses and the lack of scientific studies addressing the cellular and molecular mechanisms behind A. judaica claimed activities, the present study was designed to validate some of the traditional uses ascribed to this species, specifically the antifungal and anti-inflammatory activities of A. judaica essential oil at doses devoid of cytotoxicity to mammalian cells. 27318275 7 103 theme inhibitory 1590:1599 arg1 concentrations 1601:1614 minimal inhibitory concentrations 1582:1614 minimal inhibitory concentrations 1582:1614 The antifungal activity (minimal inhibitory concentrations and minimal lethal concentrations) was evaluated against yeasts, dermatophyte and Aspergillus strains. 27318275 4 104 theme aromatic 779:786 arg1 plant 788:792 this aromatic plant 774:792 this aromatic plant 774:792 Additionally, other folk medicines of the Arabic region commonly use this aromatic plant for the treatment of inflammatory-related diseases, for instance fungal infections, diabetes, atherosclerosis, cancer and arthritis. 27318275 9 105 from assay 2043:2047 arg1 macrophages 2073:2083 macrophages 2073:2083 macrophages 2073:2083 The assessment of cell viability was accomplished using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in both hepatocytes and macrophages. 27318275 9 105 from assay 2043:2047 arg1 hepatocytes 2057:2067 hepatocytes 2057:2067 hepatocytes 2057:2067 The assessment of cell viability was accomplished using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in both hepatocytes and macrophages. 27318275 11 106 theme RESULTS 2275:2281 arg1 group 2335:2339 a representative group 2318:2339 a representative group of constituents (68.7%) with piperitone (30.4%), camphor (16.1%) and ethyl cinnamate (11.0%) as main compounds 2318:2450 RESULTS Oxygen containing monoterpenes are a representative group of constituents (68.7%) with piperitone (30.4%), camphor (16.1%) and ethyl cinnamate (11.0%) as main compounds. 27318275 11 106 theme RESULTS 2275:2281 arg1 monoterpenes 2301:2312 RESULTS Oxygen containing monoterpenes 2275:2312 RESULTS Oxygen containing monoterpenes 2275:2312 RESULTS Oxygen containing monoterpenes are a representative group of constituents (68.7%) with piperitone (30.4%), camphor (16.1%) and ethyl cinnamate (11.0%) as main compounds. 27318275 11 106 theme RESULTS 2275:2281 arg1 constituents 2344:2355 constituents 2344:2355 constituents (68.7%) with piperitone (30.4%), camphor (16.1%) and ethyl cinnamate (11.0%) as main compounds 2344:2450 RESULTS Oxygen containing monoterpenes are a representative group of constituents (68.7%) with piperitone (30.4%), camphor (16.1%) and ethyl cinnamate (11.0%) as main compounds. 27318275 3 107 theme external 686:693 arg1 wounding 695:702 external wounding 686:702 external wounding 686:702 Furthermore, it is used for the treatment of stomach ache, heart diseases, sexual weakness, diabetes, gastro-intestinal disorders and external wounding. 27318275 18 108 theme further 3561:3567 arg1 development 3574:3584 further drug development 3561:3584 further drug development 3561:3584 Overall, A. judaica bears promising therapeutic potential for further drug development. 27318275 16 109 theme therapeutic 3249:3259 arg1 potential 3261:3269 the therapeutic potential 3245:3269 the therapeutic potential for the treatment of disseminated candidiasis 3245:3315 CONCLUSIONS The present study revealed that A. judaica essential oil from Jordan significantly inhibited germ tube formation and disrupted preformed biofilms of C. albicans, emphasizing the therapeutic potential for the treatment of disseminated candidiasis. 27318275 10 110 theme anti-inflammatory 2112:2128 arg1 potential 2130:2138 the in vitro anti-inflammatory potential 2099:2138 the in vitro anti-inflammatory potential of A. judaica oil 2099:2156 Furthermore, the in vitro anti-inflammatory potential of A. judaica oil was evaluated by measuring nitric oxide (NO) production using lipopolysaccharide (LPS)-stimulated mouse macrophages. 27318275 3 111 theme disorders 672:680 arg1 treatment 584:592 the treatment 580:592 the treatment of stomach ache, heart diseases, sexual weakness, diabetes, gastro-intestinal disorders and external wounding 580:702 Furthermore, it is used for the treatment of stomach ache, heart diseases, sexual weakness, diabetes, gastro-intestinal disorders and external wounding. 27318275 5 112 theme scientific 1003:1012 arg1 studies 1014:1020 scientific studies 1003:1020 scientific studies addressing the cellular and molecular mechanisms behind A. judaica claimed activities 1003:1106 AIM OF THE STUDY Considering the traditional medicinal uses and the lack of scientific studies addressing the cellular and molecular mechanisms behind A. judaica claimed activities, the present study was designed to validate some of the traditional uses ascribed to this species, specifically the antifungal and anti-inflammatory activities of A. judaica essential oil at doses devoid of cytotoxicity to mammalian cells. 27318275 13 113 theme important 2593:2601 arg1 effect 2614:2619 an important inhibitory effect 2590:2619 an important inhibitory effect on germ tube formation in C. albicans 2590:2657 The oil revealed an important inhibitory effect on germ tube formation in C. albicans with 80% inhibition of filamentation at a concentration of 0.16µL/mL. 27318275 7 114 theme antifungal 1561:1570 arg1 activity 1572:1579 The antifungal activity 1557:1579 The antifungal activity (minimal inhibitory concentrations and minimal lethal concentrations) 1557:1649 The antifungal activity (minimal inhibitory concentrations and minimal lethal concentrations) was evaluated against yeasts, dermatophyte and Aspergillus strains. 27318275 11 115 theme main 2437:2440 arg1 compounds 2442:2450 main compounds 2437:2450 main compounds 2437:2450 RESULTS Oxygen containing monoterpenes are a representative group of constituents (68.7%) with piperitone (30.4%), camphor (16.1%) and ethyl cinnamate (11.0%) as main compounds. 27318275 12 116 theme 0.16µL/mL 2562:2570 arg1 value 2553:2557 a MIC value 2547:2557 a MIC value of 0.16µL/mL 2547:2570 The highest antifungal activity of the oil was observed against Cryptococcus neoformans, with a MIC value of 0.16µL/mL. 27318275 14 117 theme biomass 2830:2836 arg1 amount 2807:2812 the amount 2803:2812 the amount of the attached biomass 2803:2836 Importantly, the oil also interfered with pre-formed biofilms by reducing the amount of the attached biomass. 27318275 14 117 theme biomass 2830:2836 arg1 biomass 2830:2836 the attached biomass 2817:2836 the attached biomass 2817:2836 Importantly, the oil also interfered with pre-formed biofilms by reducing the amount of the attached biomass. 27318275 1 118 theme ETHNOPHARMACOLOGIC 114:131 arg1 plant 217:221 a medicinal and aromatic plant 192:221 a medicinal and aromatic plant growing in the valley bottoms of desert areas, particularly in the southern desert of Jordan nearest to the Jordan-Saudi Arabia borders and in Wadi Araba in the Southern Badia 192:397 ETHNOPHARMACOLOGIC RELEVANCE Artemisia judaica L. (Arabic name: Beithran), is a medicinal and aromatic plant growing in the valley bottoms of desert areas, particularly in the southern desert of Jordan nearest to the Jordan-Saudi Arabia borders and in Wadi Araba in the Southern Badia. 27318275 1 118 theme ETHNOPHARMACOLOGIC 114:131 arg1 RELEVANCE 133:141 ETHNOPHARMACOLOGIC RELEVANCE 114:141 ETHNOPHARMACOLOGIC RELEVANCE Artemisia judaica L. 114:162 ETHNOPHARMACOLOGIC RELEVANCE Artemisia judaica L. (Arabic name: Beithran), is a medicinal and aromatic plant growing in the valley bottoms of desert areas, particularly in the southern desert of Jordan nearest to the Jordan-Saudi Arabia borders and in Wadi Araba in the Southern Badia. 27318275 4 119 theme inflammatory-related 815:834 arg1 diseases 836:843 inflammatory-related diseases 815:843 inflammatory-related diseases 815:843 Additionally, other folk medicines of the Arabic region commonly use this aromatic plant for the treatment of inflammatory-related diseases, for instance fungal infections, diabetes, atherosclerosis, cancer and arthritis. 27318275 5 120 from activities 1257:1266 arg1 doses 1299:1303 doses 1299:1303 doses devoid of cytotoxicity to mammalian cells 1299:1345 AIM OF THE STUDY Considering the traditional medicinal uses and the lack of scientific studies addressing the cellular and molecular mechanisms behind A. judaica claimed activities, the present study was designed to validate some of the traditional uses ascribed to this species, specifically the antifungal and anti-inflammatory activities of A. judaica essential oil at doses devoid of cytotoxicity to mammalian cells. 27318275 9 121 theme cell 1934:1937 arg1 viability 1939:1947 cell viability 1934:1947 cell viability 1934:1947 The assessment of cell viability was accomplished using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in both hepatocytes and macrophages. 27318275 16 122 theme present 3075:3081 arg1 study 3083:3087 The present study 3071:3087 The present study 3071:3087 CONCLUSIONS The present study revealed that A. judaica essential oil from Jordan significantly inhibited germ tube formation and disrupted preformed biofilms of C. albicans, emphasizing the therapeutic potential for the treatment of disseminated candidiasis. 27318275 1 123 theme Artemisia 143:151 arg1 L 161:161 Artemisia judaica L 143:161 ETHNOPHARMACOLOGIC RELEVANCE Artemisia judaica L. 114:162 ETHNOPHARMACOLOGIC RELEVANCE Artemisia judaica L. (Arabic name: Beithran), is a medicinal and aromatic plant growing in the valley bottoms of desert areas, particularly in the southern desert of Jordan nearest to the Jordan-Saudi Arabia borders and in Wadi Araba in the Southern Badia. 27318275 2 124 theme North 509:513 arg1 region 521:526 the North Badia region 505:526 the North Badia region of Jordan 505:536 In Jordan, A. judaica is widely used in traditional medicine being recommended by aboriginal Bedouins in the North Badia region of Jordan as calmative. 27318275 16 125 theme disseminated 3292:3303 arg1 candidiasis 3305:3315 disseminated candidiasis 3292:3315 disseminated candidiasis 3292:3315 CONCLUSIONS The present study revealed that A. judaica essential oil from Jordan significantly inhibited germ tube formation and disrupted preformed biofilms of C. albicans, emphasizing the therapeutic potential for the treatment of disseminated candidiasis. 27318275 14 126 theme pre-formed 2771:2780 arg1 biofilms 2782:2789 pre-formed biofilms 2771:2789 pre-formed biofilms 2771:2789 Importantly, the oil also interfered with pre-formed biofilms by reducing the amount of the attached biomass. 27318275 10 127 theme nitric 2185:2190 arg1 NO 2199:2200 NO 2199:2200 NO 2199:2200 Furthermore, the in vitro anti-inflammatory potential of A. judaica oil was evaluated by measuring nitric oxide (NO) production using lipopolysaccharide (LPS)-stimulated mouse macrophages. 27318275 10 127 theme nitric 2185:2190 arg1 oxide 2192:2196 nitric oxide 2185:2196 nitric oxide (NO) production 2185:2212 Furthermore, the in vitro anti-inflammatory potential of A. judaica oil was evaluated by measuring nitric oxide (NO) production using lipopolysaccharide (LPS)-stimulated mouse macrophages. 27318275 5 128 theme antifungal 1224:1233 arg1 activities 1257:1266 the antifungal and anti-inflammatory activities 1220:1266 the antifungal and anti-inflammatory activities of A. judaica essential oil at doses devoid of cytotoxicity to mammalian cells 1220:1345 AIM OF THE STUDY Considering the traditional medicinal uses and the lack of scientific studies addressing the cellular and molecular mechanisms behind A. judaica claimed activities, the present study was designed to validate some of the traditional uses ascribed to this species, specifically the antifungal and anti-inflammatory activities of A. judaica essential oil at doses devoid of cytotoxicity to mammalian cells. 27318275 1 129 theme Southern 384:391 arg1 Badia 393:397 the Southern Badia 380:397 the Southern Badia 380:397 ETHNOPHARMACOLOGIC RELEVANCE Artemisia judaica L. (Arabic name: Beithran), is a medicinal and aromatic plant growing in the valley bottoms of desert areas, particularly in the southern desert of Jordan nearest to the Jordan-Saudi Arabia borders and in Wadi Araba in the Southern Badia. 27318275 6 130 theme gas 1511:1513 arg1 GC-MS 1549:1553 GC-MS 1549:1553 GC-MS 1549:1553 MATERIALS AND METHODS Chemical analysis of A. judaica essential oil isolated by hydrodistillation from aerial parts was carried out by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). 27318275 6 130 theme gas 1511:1513 arg1 spectrometry 1535:1546 gas chromatography-mass spectrometry 1511:1546 gas chromatography-mass spectrometry (GC-MS) 1511:1554 MATERIALS AND METHODS Chemical analysis of A. judaica essential oil isolated by hydrodistillation from aerial parts was carried out by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). 27318275 16 131 theme preformed 3198:3206 arg1 biofilms 3208:3215 preformed biofilms 3198:3215 preformed biofilms of C. albicans 3198:3230 CONCLUSIONS The present study revealed that A. judaica essential oil from Jordan significantly inhibited germ tube formation and disrupted preformed biofilms of C. albicans, emphasizing the therapeutic potential for the treatment of disseminated candidiasis. 27318275 13 132 from effect 2614:2619 arg1 formation 2634:2642 germ tube formation 2624:2642 germ tube formation 2624:2642 The oil revealed an important inhibitory effect on germ tube formation in C. albicans with 80% inhibition of filamentation at a concentration of 0.16µL/mL. 27318275 13 132 from effect 2614:2619 arg1 albicans 2650:2657 C. albicans 2647:2657 C. albicans 2647:2657 The oil revealed an important inhibitory effect on germ tube formation in C. albicans with 80% inhibition of filamentation at a concentration of 0.16µL/mL. 27318275 6 133 attach isolated 1416:1423 arg2 oil 1412:1414 A. judaica essential oil 1391:1414 A. judaica essential oil isolated by hydrodistillation from aerial parts 1391:1462 MATERIALS AND METHODS Chemical analysis of A. judaica essential oil isolated by hydrodistillation from aerial parts was carried out by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). 27318275 6 133 attach isolated 1416:1423 arg1 parts 1458:1462 aerial parts 1451:1462 aerial parts 1451:1462 MATERIALS AND METHODS Chemical analysis of A. judaica essential oil isolated by hydrodistillation from aerial parts was carried out by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). 27318275 0 134 theme southern 87:94 arg1 desert 96:101 southern desert 87:101 southern desert of Jordan 87:111 Chemical composition and biological activities of Artemisia judaica essential oil from southern desert of Jordan. 27318275 12 135 theme Cryptococcus 2517:2528 arg1 neoformans 2530:2539 Cryptococcus neoformans 2517:2539 Cryptococcus neoformans 2517:2539 The highest antifungal activity of the oil was observed against Cryptococcus neoformans, with a MIC value of 0.16µL/mL. 27318275 8 136 theme anti-fungal 1772:1782 arg1 effect 1784:1789 the anti-fungal effect 1768:1789 the anti-fungal effect of the essential oil 1768:1810 In order to deeply explore the mechanisms behind the anti-fungal effect of the essential oil, the germ tube inhibition assay and the biofilms formation assay were evaluated using Candida albicans. 27318275 16 137 theme albicans 3223:3230 arg1 biofilms 3208:3215 preformed biofilms 3198:3215 preformed biofilms of C. albicans 3198:3230 CONCLUSIONS The present study revealed that A. judaica essential oil from Jordan significantly inhibited germ tube formation and disrupted preformed biofilms of C. albicans, emphasizing the therapeutic potential for the treatment of disseminated candidiasis. 27318275 5 138 theme cellular 1037:1044 arg1 mechanisms 1060:1069 the cellular and molecular mechanisms 1033:1069 the cellular and molecular mechanisms behind A. judaica claimed activities 1033:1106 AIM OF THE STUDY Considering the traditional medicinal uses and the lack of scientific studies addressing the cellular and molecular mechanisms behind A. judaica claimed activities, the present study was designed to validate some of the traditional uses ascribed to this species, specifically the antifungal and anti-inflammatory activities of A. judaica essential oil at doses devoid of cytotoxicity to mammalian cells. 27318275 13 139 theme 0.16µL/mL 2718:2726 arg1 concentration 2701:2713 a concentration 2699:2713 a concentration of 0.16µL/mL 2699:2726 The oil revealed an important inhibitory effect on germ tube formation in C. albicans with 80% inhibition of filamentation at a concentration of 0.16µL/mL. 27318275 11 140 theme containing 2290:2299 arg1 group 2335:2339 a representative group 2318:2339 a representative group of constituents (68.7%) with piperitone (30.4%), camphor (16.1%) and ethyl cinnamate (11.0%) as main compounds 2318:2450 RESULTS Oxygen containing monoterpenes are a representative group of constituents (68.7%) with piperitone (30.4%), camphor (16.1%) and ethyl cinnamate (11.0%) as main compounds. 27318275 11 140 theme containing 2290:2299 arg1 monoterpenes 2301:2312 RESULTS Oxygen containing monoterpenes 2275:2312 RESULTS Oxygen containing monoterpenes 2275:2312 RESULTS Oxygen containing monoterpenes are a representative group of constituents (68.7%) with piperitone (30.4%), camphor (16.1%) and ethyl cinnamate (11.0%) as main compounds. 27318275 11 140 theme containing 2290:2299 arg1 constituents 2344:2355 constituents 2344:2355 constituents (68.7%) with piperitone (30.4%), camphor (16.1%) and ethyl cinnamate (11.0%) as main compounds 2344:2450 RESULTS Oxygen containing monoterpenes are a representative group of constituents (68.7%) with piperitone (30.4%), camphor (16.1%) and ethyl cinnamate (11.0%) as main compounds. 27318275 9 141 theme -2,5-diphenyltetrazolium 2004:2027 arg1 assay 2043:2047 the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay 1972:2047 the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in both hepatocytes and macrophages 1972:2083 The assessment of cell viability was accomplished using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in both hepatocytes and macrophages. 27318275 1 142 dep RELEVANCE 133:141 arg1 name 172:175 Arabic name 165:175 Arabic name: Beithran 165:185 ETHNOPHARMACOLOGIC RELEVANCE Artemisia judaica L. (Arabic name: Beithran), is a medicinal and aromatic plant growing in the valley bottoms of desert areas, particularly in the southern desert of Jordan nearest to the Jordan-Saudi Arabia borders and in Wadi Araba in the Southern Badia. 27318275 1 142 dep RELEVANCE 133:141 arg1 L 161:161 Artemisia judaica L 143:161 ETHNOPHARMACOLOGIC RELEVANCE Artemisia judaica L. 114:162 ETHNOPHARMACOLOGIC RELEVANCE Artemisia judaica L. (Arabic name: Beithran), is a medicinal and aromatic plant growing in the valley bottoms of desert areas, particularly in the southern desert of Jordan nearest to the Jordan-Saudi Arabia borders and in Wadi Araba in the Southern Badia. 27318275 5 143 theme oil 1292:1294 arg1 activities 1257:1266 the antifungal and anti-inflammatory activities 1220:1266 the antifungal and anti-inflammatory activities of A. judaica essential oil at doses devoid of cytotoxicity to mammalian cells 1220:1345 AIM OF THE STUDY Considering the traditional medicinal uses and the lack of scientific studies addressing the cellular and molecular mechanisms behind A. judaica claimed activities, the present study was designed to validate some of the traditional uses ascribed to this species, specifically the antifungal and anti-inflammatory activities of A. judaica essential oil at doses devoid of cytotoxicity to mammalian cells. 27318275 5 144 theme molecular 1050:1058 arg1 mechanisms 1060:1069 the cellular and molecular mechanisms 1033:1069 the cellular and molecular mechanisms behind A. judaica claimed activities 1033:1106 AIM OF THE STUDY Considering the traditional medicinal uses and the lack of scientific studies addressing the cellular and molecular mechanisms behind A. judaica claimed activities, the present study was designed to validate some of the traditional uses ascribed to this species, specifically the antifungal and anti-inflammatory activities of A. judaica essential oil at doses devoid of cytotoxicity to mammalian cells. 27318275 8 145 theme essential 1798:1806 arg1 oil 1808:1810 the essential oil 1794:1810 the essential oil 1794:1810 In order to deeply explore the mechanisms behind the anti-fungal effect of the essential oil, the germ tube inhibition assay and the biofilms formation assay were evaluated using Candida albicans. 27318275 5 146 from doses 1299:1303 arg1 oil 1292:1294 A. judaica essential oil 1271:1294 A. judaica essential oil at doses devoid of cytotoxicity to mammalian cells 1271:1345 AIM OF THE STUDY Considering the traditional medicinal uses and the lack of scientific studies addressing the cellular and molecular mechanisms behind A. judaica claimed activities, the present study was designed to validate some of the traditional uses ascribed to this species, specifically the antifungal and anti-inflammatory activities of A. judaica essential oil at doses devoid of cytotoxicity to mammalian cells. 27318275 5 146 from doses 1299:1303 arg1 activities 1257:1266 the antifungal and anti-inflammatory activities 1220:1266 the antifungal and anti-inflammatory activities of A. judaica essential oil at doses devoid of cytotoxicity to mammalian cells 1220:1345 AIM OF THE STUDY Considering the traditional medicinal uses and the lack of scientific studies addressing the cellular and molecular mechanisms behind A. judaica claimed activities, the present study was designed to validate some of the traditional uses ascribed to this species, specifically the antifungal and anti-inflammatory activities of A. judaica essential oil at doses devoid of cytotoxicity to mammalian cells. 27318275 14 147 theme attached 2821:2828 arg1 biomass 2830:2836 the attached biomass 2817:2836 the attached biomass 2817:2836 Importantly, the oil also interfered with pre-formed biofilms by reducing the amount of the attached biomass. 27318275 1 148 dep Jordan 309:314 arg1 nearest 316:322 nearest 316:322 nearest to the Jordan-Saudi Arabia borders 316:357 ETHNOPHARMACOLOGIC RELEVANCE Artemisia judaica L. (Arabic name: Beithran), is a medicinal and aromatic plant growing in the valley bottoms of desert areas, particularly in the southern desert of Jordan nearest to the Jordan-Saudi Arabia borders and in Wadi Araba in the Southern Badia. 27318275 5 149 theme anti-inflammatory 1239:1255 arg1 activities 1257:1266 the antifungal and anti-inflammatory activities 1220:1266 the antifungal and anti-inflammatory activities of A. judaica essential oil at doses devoid of cytotoxicity to mammalian cells 1220:1345 AIM OF THE STUDY Considering the traditional medicinal uses and the lack of scientific studies addressing the cellular and molecular mechanisms behind A. judaica claimed activities, the present study was designed to validate some of the traditional uses ascribed to this species, specifically the antifungal and anti-inflammatory activities of A. judaica essential oil at doses devoid of cytotoxicity to mammalian cells. 27318275 0 150 theme biological 25:34 arg1 activities 36:45 biological activities 25:45 biological activities 25:45 Chemical composition and biological activities of Artemisia judaica essential oil from southern desert of Jordan. 27318275 1 151 theme desert 256:261 arg1 areas 263:267 desert areas 256:267 desert areas 256:267 ETHNOPHARMACOLOGIC RELEVANCE Artemisia judaica L. (Arabic name: Beithran), is a medicinal and aromatic plant growing in the valley bottoms of desert areas, particularly in the southern desert of Jordan nearest to the Jordan-Saudi Arabia borders and in Wadi Araba in the Southern Badia. 27318275 18 152 theme therapeutic 3535:3545 arg1 potential 3547:3555 promising therapeutic potential 3525:3555 promising therapeutic potential for further drug development 3525:3584 Overall, A. judaica bears promising therapeutic potential for further drug development. 27318275 10 153 dep A. 2143:2144 arg1 judaica 2146:2152 judaica 2146:2152 judaica 2146:2152 Furthermore, the in vitro anti-inflammatory potential of A. judaica oil was evaluated by measuring nitric oxide (NO) production using lipopolysaccharide (LPS)-stimulated mouse macrophages. 27318275 15 154 theme NO 2894:2895 arg1 production 2897:2906 NO production 2894:2906 NO production evoked by LPS 2894:2920 Furthermore, the essential oil significantly inhibited NO production evoked by LPS on macrophages at concentrations with very low toxicity (0.32µL/mL) or without toxicity (0.16µL/mL) to both macrophages and hepatocytes. 27318275 6 155 theme Chemical 1370:1377 arg1 analysis 1379:1386 MATERIALS AND METHODS Chemical analysis 1348:1386 MATERIALS AND METHODS Chemical analysis of A. judaica essential oil isolated by hydrodistillation from aerial parts 1348:1462 MATERIALS AND METHODS Chemical analysis of A. judaica essential oil isolated by hydrodistillation from aerial parts was carried out by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). 27318275 7 156 theme minimal 1620:1626 arg1 concentrations 1635:1648 minimal lethal concentrations 1620:1648 minimal lethal concentrations 1620:1648 The antifungal activity (minimal inhibitory concentrations and minimal lethal concentrations) was evaluated against yeasts, dermatophyte and Aspergillus strains. 27318275 17 157 theme essential 3360:3368 arg1 oil 3370:3372 this essential oil 3355:3372 this essential oil 3355:3372 Additionally, safe concentrations of this essential oil significantly inhibited NO production elicited by LPS in macrophages, highlighting its potential anti-inflammatory activity. 27318275 4 158 dep instance 850:857 arg1 infections 866:875 fungal infections 859:875 fungal infections 859:875 Additionally, other folk medicines of the Arabic region commonly use this aromatic plant for the treatment of inflammatory-related diseases, for instance fungal infections, diabetes, atherosclerosis, cancer and arthritis. 27318275 17 159 theme oil 3370:3372 arg1 concentrations 3337:3350 safe concentrations 3332:3350 safe concentrations of this essential oil 3332:3372 Additionally, safe concentrations of this essential oil significantly inhibited NO production elicited by LPS in macrophages, highlighting its potential anti-inflammatory activity. 27318275 3 160 theme ache 605:608 arg1 treatment 584:592 the treatment 580:592 the treatment of stomach ache, heart diseases, sexual weakness, diabetes, gastro-intestinal disorders and external wounding 580:702 Furthermore, it is used for the treatment of stomach ache, heart diseases, sexual weakness, diabetes, gastro-intestinal disorders and external wounding. 27318275 4 161 theme region 754:759 arg1 medicines 730:738 other folk medicines 719:738 other folk medicines of the Arabic region 719:759 Additionally, other folk medicines of the Arabic region commonly use this aromatic plant for the treatment of inflammatory-related diseases, for instance fungal infections, diabetes, atherosclerosis, cancer and arthritis. 27318275 1 162 theme southern 290:297 arg1 desert 299:304 the southern desert 286:304 the southern desert of Jordan nearest to the Jordan-Saudi Arabia borders 286:357 ETHNOPHARMACOLOGIC RELEVANCE Artemisia judaica L. (Arabic name: Beithran), is a medicinal and aromatic plant growing in the valley bottoms of desert areas, particularly in the southern desert of Jordan nearest to the Jordan-Saudi Arabia borders and in Wadi Araba in the Southern Badia. 27318275 12 163 theme oil 2492:2494 arg1 activity 2476:2483 The highest antifungal activity 2453:2483 The highest antifungal activity of the oil 2453:2494 The highest antifungal activity of the oil was observed against Cryptococcus neoformans, with a MIC value of 0.16µL/mL. 27318275 12 164 theme highest 2457:2463 arg1 activity 2476:2483 The highest antifungal activity 2453:2483 The highest antifungal activity of the oil 2453:2494 The highest antifungal activity of the oil was observed against Cryptococcus neoformans, with a MIC value of 0.16µL/mL. 27318275 17 165 theme anti-inflammatory 3471:3487 arg1 activity 3489:3496 its potential anti-inflammatory activity 3457:3496 its potential anti-inflammatory activity 3457:3496 Additionally, safe concentrations of this essential oil significantly inhibited NO production elicited by LPS in macrophages, highlighting its potential anti-inflammatory activity. 27318275 4 166 theme other 719:723 arg1 medicines 730:738 other folk medicines 719:738 other folk medicines of the Arabic region 719:759 Additionally, other folk medicines of the Arabic region commonly use this aromatic plant for the treatment of inflammatory-related diseases, for instance fungal infections, diabetes, atherosclerosis, cancer and arthritis. 27318275 13 167 theme 80 2664:2665 arg1 % 2666:2666 % 2666:2666 % 2666:2666 The oil revealed an important inhibitory effect on germ tube formation in C. albicans with 80% inhibition of filamentation at a concentration of 0.16µL/mL. 27318275 1 168 theme aromatic 208:215 arg1 plant 217:221 a medicinal and aromatic plant 192:221 a medicinal and aromatic plant growing in the valley bottoms of desert areas, particularly in the southern desert of Jordan nearest to the Jordan-Saudi Arabia borders and in Wadi Araba in the Southern Badia 192:397 ETHNOPHARMACOLOGIC RELEVANCE Artemisia judaica L. (Arabic name: Beithran), is a medicinal and aromatic plant growing in the valley bottoms of desert areas, particularly in the southern desert of Jordan nearest to the Jordan-Saudi Arabia borders and in Wadi Araba in the Southern Badia. 27318275 1 168 theme aromatic 208:215 arg1 RELEVANCE 133:141 ETHNOPHARMACOLOGIC RELEVANCE 114:141 ETHNOPHARMACOLOGIC RELEVANCE Artemisia judaica L. 114:162 ETHNOPHARMACOLOGIC RELEVANCE Artemisia judaica L. (Arabic name: Beithran), is a medicinal and aromatic plant growing in the valley bottoms of desert areas, particularly in the southern desert of Jordan nearest to the Jordan-Saudi Arabia borders and in Wadi Araba in the Southern Badia. 27318275 5 169 dep A. 1271:1272 arg1 judaica 1274:1280 judaica 1274:1280 judaica 1274:1280 AIM OF THE STUDY Considering the traditional medicinal uses and the lack of scientific studies addressing the cellular and molecular mechanisms behind A. judaica claimed activities, the present study was designed to validate some of the traditional uses ascribed to this species, specifically the antifungal and anti-inflammatory activities of A. judaica essential oil at doses devoid of cytotoxicity to mammalian cells. 27318275 13 170 theme tube 2629:2632 arg1 formation 2634:2642 germ tube formation 2624:2642 germ tube formation 2624:2642 The oil revealed an important inhibitory effect on germ tube formation in C. albicans with 80% inhibition of filamentation at a concentration of 0.16µL/mL. 28935101 1 0 link O-linked 231:238 arg1 glycoproteins 240:252 O-linked glycoproteins 231:252 O-linked glycoproteins 231:252 This method describes the chemoenzymatic synthesis of several nucleotide sugars, which are essential substrates in the biosynthesis of prokaryotic N- and O-linked glycoproteins. 28935101 1 1 from substrates 178:187 arg1 biosynthesis 196:207 the biosynthesis 192:207 the biosynthesis of prokaryotic N- and O-linked glycoproteins 192:252 This method describes the chemoenzymatic synthesis of several nucleotide sugars, which are essential substrates in the biosynthesis of prokaryotic N- and O-linked glycoproteins. 28935101 3 2 theme glycoconjugates 636:650 arg1 components 593:602 important components 583:602 important components of other bacterial and archaeal glycoconjugates 583:650 The latter, which include UDP-hexoses such as UDP-diNAc-bacillosamine (UDP-diNAcBac), UDP-diNAcAlt, and UDP-2,3-diNAcManA, are also important components of other bacterial and archaeal glycoconjugates. 28935101 3 2 theme glycoconjugates 636:650 arg1 latter 455:460 latter 455:460 latter 455:460 The latter, which include UDP-hexoses such as UDP-diNAc-bacillosamine (UDP-diNAcBac), UDP-diNAcAlt, and UDP-2,3-diNAcManA, are also important components of other bacterial and archaeal glycoconjugates. 28935101 3 3 theme bacterial 613:621 arg1 glycoconjugates 636:650 other bacterial and archaeal glycoconjugates 607:650 other bacterial and archaeal glycoconjugates 607:650 The latter, which include UDP-hexoses such as UDP-diNAc-bacillosamine (UDP-diNAcBac), UDP-diNAcAlt, and UDP-2,3-diNAcManA, are also important components of other bacterial and archaeal glycoconjugates. 28935101 4 4 theme ready 657:661 arg1 availability 663:674 The ready availability 653:674 The ready availability of these "high-value" intermediates 653:710 The ready availability of these "high-value" intermediates will enable courses of study into inhibitor screening, glycoconjugate biosynthesis pathway discovery, and unnatural carbohydrate incorporation toward metabolic engineering. 28935101 4 5 theme pathway 795:801 arg1 discovery 803:811 glycoconjugate biosynthesis pathway discovery 767:811 glycoconjugate biosynthesis pathway discovery 767:811 The ready availability of these "high-value" intermediates will enable courses of study into inhibitor screening, glycoconjugate biosynthesis pathway discovery, and unnatural carbohydrate incorporation toward metabolic engineering. 28935101 4 6 theme biosynthesis 782:793 arg1 discovery 803:811 glycoconjugate biosynthesis pathway discovery 767:811 glycoconjugate biosynthesis pathway discovery 767:811 The ready availability of these "high-value" intermediates will enable courses of study into inhibitor screening, glycoconjugate biosynthesis pathway discovery, and unnatural carbohydrate incorporation toward metabolic engineering. 28935101 4 7 theme study 735:739 arg1 courses 724:730 courses 724:730 courses of study into inhibitor screening, glycoconjugate biosynthesis pathway discovery, and unnatural carbohydrate incorporation toward metabolic engineering 724:882 The ready availability of these "high-value" intermediates will enable courses of study into inhibitor screening, glycoconjugate biosynthesis pathway discovery, and unnatural carbohydrate incorporation toward metabolic engineering. 28935101 3 8 theme important 583:591 arg1 components 593:602 important components 583:602 important components of other bacterial and archaeal glycoconjugates 583:650 The latter, which include UDP-hexoses such as UDP-diNAc-bacillosamine (UDP-diNAcBac), UDP-diNAcAlt, and UDP-2,3-diNAcManA, are also important components of other bacterial and archaeal glycoconjugates. 28935101 3 8 theme important 583:591 arg1 latter 455:460 latter 455:460 latter 455:460 The latter, which include UDP-hexoses such as UDP-diNAc-bacillosamine (UDP-diNAcBac), UDP-diNAcAlt, and UDP-2,3-diNAcManA, are also important components of other bacterial and archaeal glycoconjugates. 28935101 4 9 theme carbohydrate 828:839 arg1 incorporation 841:853 unnatural carbohydrate incorporation 818:853 unnatural carbohydrate incorporation toward metabolic engineering 818:882 The ready availability of these "high-value" intermediates will enable courses of study into inhibitor screening, glycoconjugate biosynthesis pathway discovery, and unnatural carbohydrate incorporation toward metabolic engineering. 28935101 2 10 theme sugar 432:436 arg1 nucleotides 438:448 both common and modified prokaryote-specific sugar nucleotides 387:448 both common and modified prokaryote-specific sugar nucleotides 387:448 Protein glycosylation is now known to be widespread in prokaryotes and proceeds via sequential action of several enzymes, utilizing both common and modified prokaryote-specific sugar nucleotides. 28935101 1 11 gly glycoproteins 240:252 arg1 glycoproteins 240:252 O-linked glycoproteins 231:252 O-linked glycoproteins 231:252 This method describes the chemoenzymatic synthesis of several nucleotide sugars, which are essential substrates in the biosynthesis of prokaryotic N- and O-linked glycoproteins. 28935101 1 12 theme chemoenzymatic 103:116 arg1 synthesis 118:126 the chemoenzymatic synthesis 99:126 the chemoenzymatic synthesis of several nucleotide sugars, which are essential substrates in the biosynthesis of prokaryotic N- and O-linked glycoproteins 99:252 This method describes the chemoenzymatic synthesis of several nucleotide sugars, which are essential substrates in the biosynthesis of prokaryotic N- and O-linked glycoproteins. 28935101 2 13 theme prokaryote-specific 412:430 arg1 nucleotides 438:448 both common and modified prokaryote-specific sugar nucleotides 387:448 both common and modified prokaryote-specific sugar nucleotides 387:448 Protein glycosylation is now known to be widespread in prokaryotes and proceeds via sequential action of several enzymes, utilizing both common and modified prokaryote-specific sugar nucleotides. 28935101 0 14 theme Chemoenzymatic 0:13 arg1 Synthesis 15:23 Chemoenzymatic Synthesis 0:23 Chemoenzymatic Synthesis 0:23 Chemoenzymatic Synthesis and Applications of Prokaryote-Specific UDP-Sugars. 28935101 2 15 theme sequential 339:348 arg1 action 350:355 sequential action 339:355 sequential action of several enzymes, utilizing both common and modified prokaryote-specific sugar nucleotides 339:448 Protein glycosylation is now known to be widespread in prokaryotes and proceeds via sequential action of several enzymes, utilizing both common and modified prokaryote-specific sugar nucleotides. 28935101 2 16 theme modified 403:410 arg1 nucleotides 438:448 both common and modified prokaryote-specific sugar nucleotides 387:448 both common and modified prokaryote-specific sugar nucleotides 387:448 Protein glycosylation is now known to be widespread in prokaryotes and proceeds via sequential action of several enzymes, utilizing both common and modified prokaryote-specific sugar nucleotides. 28935101 3 17 theme other 607:611 arg1 glycoconjugates 636:650 other bacterial and archaeal glycoconjugates 607:650 other bacterial and archaeal glycoconjugates 607:650 The latter, which include UDP-hexoses such as UDP-diNAc-bacillosamine (UDP-diNAcBac), UDP-diNAcAlt, and UDP-2,3-diNAcManA, are also important components of other bacterial and archaeal glycoconjugates. 28935101 1 18 theme N- 224:225 arg1 biosynthesis 196:207 the biosynthesis 192:207 the biosynthesis of prokaryotic N- and O-linked glycoproteins 192:252 This method describes the chemoenzymatic synthesis of several nucleotide sugars, which are essential substrates in the biosynthesis of prokaryotic N- and O-linked glycoproteins. 28935101 3 19 theme archaeal 627:634 arg1 glycoconjugates 636:650 other bacterial and archaeal glycoconjugates 607:650 other bacterial and archaeal glycoconjugates 607:650 The latter, which include UDP-hexoses such as UDP-diNAc-bacillosamine (UDP-diNAcBac), UDP-diNAcAlt, and UDP-2,3-diNAcManA, are also important components of other bacterial and archaeal glycoconjugates. 28935101 1 20 theme several 131:137 arg1 substrates 178:187 essential substrates 168:187 essential substrates 168:187 This method describes the chemoenzymatic synthesis of several nucleotide sugars, which are essential substrates in the biosynthesis of prokaryotic N- and O-linked glycoproteins. 28935101 1 20 theme several 131:137 arg1 sugars 150:155 several nucleotide sugars 131:155 several nucleotide sugars 131:155 This method describes the chemoenzymatic synthesis of several nucleotide sugars, which are essential substrates in the biosynthesis of prokaryotic N- and O-linked glycoproteins. 28935101 4 21 theme high-value 686:695 arg1 intermediates 698:710 these "high-value" intermediates 679:710 these "high-value" intermediates 679:710 The ready availability of these "high-value" intermediates will enable courses of study into inhibitor screening, glycoconjugate biosynthesis pathway discovery, and unnatural carbohydrate incorporation toward metabolic engineering. 28935101 0 22 theme Prokaryote-Specific 45:63 arg1 UDP-Sugars 65:74 Prokaryote-Specific UDP-Sugars 45:74 Prokaryote-Specific UDP-Sugars 45:74 Chemoenzymatic Synthesis and Applications of Prokaryote-Specific UDP-Sugars. 28935101 2 23 theme enzymes 368:374 arg1 action 350:355 sequential action 339:355 sequential action of several enzymes, utilizing both common and modified prokaryote-specific sugar nucleotides 339:448 Protein glycosylation is now known to be widespread in prokaryotes and proceeds via sequential action of several enzymes, utilizing both common and modified prokaryote-specific sugar nucleotides. 28935101 1 24 theme prokaryotic 212:222 arg1 N- 224:225 prokaryotic N- 212:225 prokaryotic N- 212:225 This method describes the chemoenzymatic synthesis of several nucleotide sugars, which are essential substrates in the biosynthesis of prokaryotic N- and O-linked glycoproteins. 28935101 1 25 theme O-linked 231:238 arg1 glycoproteins 240:252 O-linked glycoproteins 231:252 O-linked glycoproteins 231:252 This method describes the chemoenzymatic synthesis of several nucleotide sugars, which are essential substrates in the biosynthesis of prokaryotic N- and O-linked glycoproteins. 28935101 1 26 theme glycoproteins 240:252 arg1 biosynthesis 196:207 the biosynthesis 192:207 the biosynthesis of prokaryotic N- and O-linked glycoproteins 192:252 This method describes the chemoenzymatic synthesis of several nucleotide sugars, which are essential substrates in the biosynthesis of prokaryotic N- and O-linked glycoproteins. 28935101 2 27 theme Protein 255:261 arg1 glycosylation 263:275 Protein glycosylation 255:275 Protein glycosylation 255:275 Protein glycosylation is now known to be widespread in prokaryotes and proceeds via sequential action of several enzymes, utilizing both common and modified prokaryote-specific sugar nucleotides. 28935101 1 28 theme nucleotide 139:148 arg1 substrates 178:187 essential substrates 168:187 essential substrates 168:187 This method describes the chemoenzymatic synthesis of several nucleotide sugars, which are essential substrates in the biosynthesis of prokaryotic N- and O-linked glycoproteins. 28935101 1 28 theme nucleotide 139:148 arg1 sugars 150:155 several nucleotide sugars 131:155 several nucleotide sugars 131:155 This method describes the chemoenzymatic synthesis of several nucleotide sugars, which are essential substrates in the biosynthesis of prokaryotic N- and O-linked glycoproteins. 28935101 0 29 theme UDP-Sugars 65:74 arg1 Applications 29:40 Applications 29:40 Applications 29:40 Chemoenzymatic Synthesis and Applications of Prokaryote-Specific UDP-Sugars. 28935101 0 29 theme UDP-Sugars 65:74 arg1 Synthesis 15:23 Chemoenzymatic Synthesis 0:23 Chemoenzymatic Synthesis 0:23 Chemoenzymatic Synthesis and Applications of Prokaryote-Specific UDP-Sugars. 28935101 1 30 theme sugars 150:155 arg1 synthesis 118:126 the chemoenzymatic synthesis 99:126 the chemoenzymatic synthesis of several nucleotide sugars, which are essential substrates in the biosynthesis of prokaryotic N- and O-linked glycoproteins 99:252 This method describes the chemoenzymatic synthesis of several nucleotide sugars, which are essential substrates in the biosynthesis of prokaryotic N- and O-linked glycoproteins. 28935101 2 31 theme several 360:366 arg1 enzymes 368:374 several enzymes 360:374 several enzymes 360:374 Protein glycosylation is now known to be widespread in prokaryotes and proceeds via sequential action of several enzymes, utilizing both common and modified prokaryote-specific sugar nucleotides. 28935101 2 32 from widespread 296:305 arg1 prokaryotes 310:320 prokaryotes 310:320 prokaryotes 310:320 Protein glycosylation is now known to be widespread in prokaryotes and proceeds via sequential action of several enzymes, utilizing both common and modified prokaryote-specific sugar nucleotides. 28935101 4 33 theme metabolic 862:870 arg1 engineering 872:882 metabolic engineering 862:882 metabolic engineering 862:882 The ready availability of these "high-value" intermediates will enable courses of study into inhibitor screening, glycoconjugate biosynthesis pathway discovery, and unnatural carbohydrate incorporation toward metabolic engineering. 28935101 4 34 theme unnatural 818:826 arg1 incorporation 841:853 unnatural carbohydrate incorporation 818:853 unnatural carbohydrate incorporation toward metabolic engineering 818:882 The ready availability of these "high-value" intermediates will enable courses of study into inhibitor screening, glycoconjugate biosynthesis pathway discovery, and unnatural carbohydrate incorporation toward metabolic engineering. 28935101 1 35 theme essential 168:176 arg1 substrates 178:187 essential substrates 168:187 essential substrates 168:187 This method describes the chemoenzymatic synthesis of several nucleotide sugars, which are essential substrates in the biosynthesis of prokaryotic N- and O-linked glycoproteins. 28935101 1 35 theme essential 168:176 arg1 sugars 150:155 several nucleotide sugars 131:155 several nucleotide sugars 131:155 This method describes the chemoenzymatic synthesis of several nucleotide sugars, which are essential substrates in the biosynthesis of prokaryotic N- and O-linked glycoproteins. 28935101 4 36 theme intermediates 698:710 arg1 availability 663:674 The ready availability 653:674 The ready availability of these "high-value" intermediates 653:710 The ready availability of these "high-value" intermediates will enable courses of study into inhibitor screening, glycoconjugate biosynthesis pathway discovery, and unnatural carbohydrate incorporation toward metabolic engineering. 28935101 4 37 theme " 696:696 arg1 intermediates 698:710 these "high-value" intermediates 679:710 these "high-value" intermediates 679:710 The ready availability of these "high-value" intermediates will enable courses of study into inhibitor screening, glycoconjugate biosynthesis pathway discovery, and unnatural carbohydrate incorporation toward metabolic engineering. 28935101 4 38 theme inhibitor 746:754 arg1 screening 756:764 inhibitor screening 746:764 inhibitor screening 746:764 The ready availability of these "high-value" intermediates will enable courses of study into inhibitor screening, glycoconjugate biosynthesis pathway discovery, and unnatural carbohydrate incorporation toward metabolic engineering. 28935101 2 39 from prokaryotes 310:320 arg1 widespread 296:305 widespread 296:305 widespread 296:305 Protein glycosylation is now known to be widespread in prokaryotes and proceeds via sequential action of several enzymes, utilizing both common and modified prokaryote-specific sugar nucleotides. 28935101 2 40 theme common 392:397 arg1 nucleotides 438:448 both common and modified prokaryote-specific sugar nucleotides 387:448 both common and modified prokaryote-specific sugar nucleotides 387:448 Protein glycosylation is now known to be widespread in prokaryotes and proceeds via sequential action of several enzymes, utilizing both common and modified prokaryote-specific sugar nucleotides. 28935101 4 41 theme glycoconjugate 767:780 arg1 discovery 803:811 glycoconjugate biosynthesis pathway discovery 767:811 glycoconjugate biosynthesis pathway discovery 767:811 The ready availability of these "high-value" intermediates will enable courses of study into inhibitor screening, glycoconjugate biosynthesis pathway discovery, and unnatural carbohydrate incorporation toward metabolic engineering. 26606450 2 0 theme migratory 357:365 arg1 properties 367:376 the tumoritropic migratory properties 340:376 the tumoritropic migratory properties of particular cell types 340:401 Cell-mediated delivery of nanoparticles (NPs) is promising in terms of overcoming several of these barriers based on the tumoritropic migratory properties of particular cell types. 26606450 6 1 theme lymphocytes 1001:1011 arg1 surface 978:984 the surface 974:984 the surface of cytotoxic T lymphocytes 974:1011 This proof-of-concept therefore reports on the reversible attachment of liposomes to the surface of cytotoxic T lymphocytes via a reduction sensitive coupling. 26606450 0 2 theme T 89:89 arg1 lymphocytes 91:101 cytotoxic T lymphocytes 79:101 cytotoxic T lymphocytes 79:101 Hitchhiking nanoparticles: Reversible coupling of lipid-based nanoparticles to cytotoxic T lymphocytes. 26606450 9 3 theme triggered 1308:1316 arg1 release 1327:1333 the triggered liposome release 1304:1333 the triggered liposome release 1304:1333 Additionally, the triggered liposome release is demonstrated upon the addition of glutathione. 26606450 8 4 dep Loading 1171:1177 arg1 cells 1183:1187 the cells 1179:1187 Loading the cells with liposomes 1171:1202 Loading the cells with liposomes does not compromise T cell functionalities like proliferation and cytolytic function. 26606450 8 5 theme T 1224:1224 arg1 functionalities 1231:1245 T cell functionalities 1224:1245 T cell functionalities like proliferation and cytolytic function 1224:1287 Loading the cells with liposomes does not compromise T cell functionalities like proliferation and cytolytic function. 26606450 2 6 theme tumoritropic 344:355 arg1 properties 367:376 the tumoritropic migratory properties 340:376 the tumoritropic migratory properties of particular cell types 340:401 Cell-mediated delivery of nanoparticles (NPs) is promising in terms of overcoming several of these barriers based on the tumoritropic migratory properties of particular cell types. 26606450 6 7 theme T 999:999 arg1 lymphocytes 1001:1011 cytotoxic T lymphocytes 989:1011 cytotoxic T lymphocytes 989:1011 This proof-of-concept therefore reports on the reversible attachment of liposomes to the surface of cytotoxic T lymphocytes via a reduction sensitive coupling. 26606450 10 8 theme cells 1545:1549 arg1 surface 1525:1531 the surface 1521:1531 the surface of CD8(+) T cells 1521:1549 Based on this optimization using liposomes as model NPs, a small interfering RNA (siRNA)-loaded NP was developed that can be coupled to the surface of CD8(+) T cells. 26606450 9 9 theme liposome 1318:1325 arg1 release 1327:1333 the triggered liposome release 1304:1333 the triggered liposome release 1304:1333 Additionally, the triggered liposome release is demonstrated upon the addition of glutathione. 26606450 10 10 theme interfering 1450:1460 arg1 RNA 1462:1464 a small interfering RNA 1442:1464 a small interfering RNA (siRNA)-loaded NP 1442:1482 Based on this optimization using liposomes as model NPs, a small interfering RNA (siRNA)-loaded NP was developed that can be coupled to the surface of CD8(+) T cells. 26606450 10 10 theme interfering 1450:1460 arg1 siRNA 1467:1471 siRNA 1467:1471 siRNA 1467:1471 Based on this optimization using liposomes as model NPs, a small interfering RNA (siRNA)-loaded NP was developed that can be coupled to the surface of CD8(+) T cells. 26606450 4 11 theme cytotoxic 589:597 arg1 CD8 599:601 cytotoxic CD8 589:601 cytotoxic CD8 589:601 Within this study, cytotoxic CD8(+) T cells were selected as carriers based on both their ability to migrate to the tumor and their intrinsic cytolytic activity against tumor cells. 26606450 10 12 theme T 1543:1543 arg1 cells 1545:1549 CD8(+) T cells 1536:1549 CD8(+) T cells 1536:1549 Based on this optimization using liposomes as model NPs, a small interfering RNA (siRNA)-loaded NP was developed that can be coupled to the surface of CD8(+) T cells. 26606450 3 13 theme free 560:563 arg1 NPs 565:567 free NPs 560:567 free NPs 560:567 This guided transport aims to enhance the NP accumulation in the tumor and moreover enhance the infiltration of regions that are typically inaccessible for free NPs. 26606450 4 14 theme T 606:606 arg1 carriers 631:638 carriers 631:638 carriers based on both their ability to migrate to the tumor and their intrinsic cytolytic activity against tumor cells 631:749 Within this study, cytotoxic CD8(+) T cells were selected as carriers based on both their ability to migrate to the tumor and their intrinsic cytolytic activity against tumor cells. 26606450 4 14 theme T 606:606 arg1 cells 608:612 cytotoxic CD8(+) T cells 589:612 cytotoxic CD8(+) T cells 589:612 Within this study, cytotoxic CD8(+) T cells were selected as carriers based on both their ability to migrate to the tumor and their intrinsic cytolytic activity against tumor cells. 26606450 10 15 theme RNA 1462:1464 arg1 NP 1481:1482 a small interfering RNA (siRNA)-loaded NP 1442:1482 a small interfering RNA (siRNA)-loaded NP 1442:1482 Based on this optimization using liposomes as model NPs, a small interfering RNA (siRNA)-loaded NP was developed that can be coupled to the surface of CD8(+) T cells. 26606450 3 16 theme guided 409:414 arg1 transport 416:424 This guided transport 404:424 This guided transport 404:424 This guided transport aims to enhance the NP accumulation in the tumor and moreover enhance the infiltration of regions that are typically inaccessible for free NPs. 26606450 7 17 theme liposome 1094:1101 arg1 composition 1103:1113 the liposome composition 1090:1113 the liposome composition 1090:1113 The activation status of the T cells and the liposome composition are shown to strongly influence the loading efficiency. 26606450 4 18 theme tumor 739:743 arg1 cells 745:749 tumor cells 739:749 tumor cells 739:749 Within this study, cytotoxic CD8(+) T cells were selected as carriers based on both their ability to migrate to the tumor and their intrinsic cytolytic activity against tumor cells. 26606450 2 19 theme types 397:401 arg1 properties 367:376 the tumoritropic migratory properties 340:376 the tumoritropic migratory properties of particular cell types 340:401 Cell-mediated delivery of nanoparticles (NPs) is promising in terms of overcoming several of these barriers based on the tumoritropic migratory properties of particular cell types. 26606450 9 20 theme glutathione 1372:1382 arg1 addition 1360:1367 the addition 1356:1367 the addition of glutathione 1356:1382 Additionally, the triggered liposome release is demonstrated upon the addition of glutathione. 26606450 7 21 theme cells 1080:1084 arg1 composition 1103:1113 the liposome composition 1090:1113 the liposome composition 1090:1113 The activation status of the T cells and the liposome composition are shown to strongly influence the loading efficiency. 26606450 7 21 theme cells 1080:1084 arg1 status 1064:1069 The activation status 1049:1069 The activation status of the T cells 1049:1084 The activation status of the T cells and the liposome composition are shown to strongly influence the loading efficiency. 26606450 10 22 theme small 1444:1448 arg1 RNA 1462:1464 a small interfering RNA 1442:1464 a small interfering RNA (siRNA)-loaded NP 1442:1482 Based on this optimization using liposomes as model NPs, a small interfering RNA (siRNA)-loaded NP was developed that can be coupled to the surface of CD8(+) T cells. 26606450 10 22 theme small 1444:1448 arg1 siRNA 1467:1471 siRNA 1467:1471 siRNA 1467:1471 Based on this optimization using liposomes as model NPs, a small interfering RNA (siRNA)-loaded NP was developed that can be coupled to the surface of CD8(+) T cells. 26606450 2 23 theme cell 392:395 arg1 types 397:401 particular cell types 381:401 particular cell types 381:401 Cell-mediated delivery of nanoparticles (NPs) is promising in terms of overcoming several of these barriers based on the tumoritropic migratory properties of particular cell types. 26606450 0 24 theme Hitchhiking 0:10 arg1 nanoparticles 12:24 Hitchhiking nanoparticles 0:24 Hitchhiking nanoparticles 0:24 Hitchhiking nanoparticles: Reversible coupling of lipid-based nanoparticles to cytotoxic T lymphocytes. 26606450 8 25 theme cytolytic 1270:1278 arg1 function 1280:1287 cytolytic function 1270:1287 cytolytic function 1270:1287 Loading the cells with liposomes does not compromise T cell functionalities like proliferation and cytolytic function. 26606450 2 26 theme particular 381:390 arg1 types 397:401 particular cell types 381:401 particular cell types 381:401 Cell-mediated delivery of nanoparticles (NPs) is promising in terms of overcoming several of these barriers based on the tumoritropic migratory properties of particular cell types. 26606450 0 27 theme Reversible 27:36 arg1 coupling 38:45 Reversible coupling 27:45 Reversible coupling of lipid-based nanoparticles to cytotoxic T lymphocytes 27:101 Hitchhiking nanoparticles: Reversible coupling of lipid-based nanoparticles to cytotoxic T lymphocytes. 26606450 5 28 theme tumor 791:795 arg1 internalization 802:816 tumor cell internalization 791:816 tumor cell internalization 791:816 Many anti-cancer nanomedicines require tumor cell internalization to mediate cytosolic drug delivery and enhance the anti-cancer effect. 26606450 0 29 dep coupling 38:45 arg1 nanoparticles 12:24 Hitchhiking nanoparticles 0:24 Hitchhiking nanoparticles 0:24 Hitchhiking nanoparticles: Reversible coupling of lipid-based nanoparticles to cytotoxic T lymphocytes. 26606450 1 30 theme intravenous 114:124 arg1 injection 126:134 intravenous injection 114:134 intravenous injection of anti-cancer nanomedicines 114:163 Following intravenous injection of anti-cancer nanomedicines, many barriers need to be overcome en route to the tumor. 26606450 6 31 attach attachment 947:956 arg2 liposomes 961:969 liposomes 961:969 liposomes 961:969 This proof-of-concept therefore reports on the reversible attachment of liposomes to the surface of cytotoxic T lymphocytes via a reduction sensitive coupling. 26606450 6 31 attach attachment 947:956 arg1 surface 978:984 the surface 974:984 the surface of cytotoxic T lymphocytes 974:1011 This proof-of-concept therefore reports on the reversible attachment of liposomes to the surface of cytotoxic T lymphocytes via a reduction sensitive coupling. 26606450 7 32 theme T 1078:1078 arg1 cells 1080:1084 the T cells 1074:1084 the T cells 1074:1084 The activation status of the T cells and the liposome composition are shown to strongly influence the loading efficiency. 26606450 4 33 theme intrinsic 702:710 arg1 activity 722:729 their intrinsic cytolytic activity 696:729 their intrinsic cytolytic activity against tumor cells 696:749 Within this study, cytotoxic CD8(+) T cells were selected as carriers based on both their ability to migrate to the tumor and their intrinsic cytolytic activity against tumor cells. 26606450 1 34 theme many 166:169 arg1 barriers 171:178 many barriers 166:178 many barriers 166:178 Following intravenous injection of anti-cancer nanomedicines, many barriers need to be overcome en route to the tumor. 26606450 6 35 theme liposomes 961:969 arg1 attachment 947:956 the reversible attachment 932:956 the reversible attachment of liposomes to the surface of cytotoxic T lymphocytes 932:1011 This proof-of-concept therefore reports on the reversible attachment of liposomes to the surface of cytotoxic T lymphocytes via a reduction sensitive coupling. 26606450 2 36 theme nanoparticles 249:261 arg1 delivery 237:244 Cell-mediated delivery 223:244 Cell-mediated delivery of nanoparticles (NPs) 223:267 Cell-mediated delivery of nanoparticles (NPs) is promising in terms of overcoming several of these barriers based on the tumoritropic migratory properties of particular cell types. 26606450 5 37 theme cytosolic 829:837 arg1 delivery 844:851 cytosolic drug delivery 829:851 cytosolic drug delivery 829:851 Many anti-cancer nanomedicines require tumor cell internalization to mediate cytosolic drug delivery and enhance the anti-cancer effect. 26606450 5 38 theme Many 752:755 arg1 nanomedicines 769:781 Many anti-cancer nanomedicines 752:781 Many anti-cancer nanomedicines 752:781 Many anti-cancer nanomedicines require tumor cell internalization to mediate cytosolic drug delivery and enhance the anti-cancer effect. 26606450 7 39 theme loading 1151:1157 arg1 efficiency 1159:1168 the loading efficiency 1147:1168 the loading efficiency 1147:1168 The activation status of the T cells and the liposome composition are shown to strongly influence the loading efficiency. 26606450 3 40 dep enhance 434:440 arg1 enhance 488:494 enhance 488:494 enhance the infiltration of regions that are typically inaccessible for free NPs 488:567 This guided transport aims to enhance the NP accumulation in the tumor and moreover enhance the infiltration of regions that are typically inaccessible for free NPs. 26606450 3 41 from accumulation 449:460 arg1 tumor 469:473 the tumor 465:473 the tumor 465:473 This guided transport aims to enhance the NP accumulation in the tumor and moreover enhance the infiltration of regions that are typically inaccessible for free NPs. 26606450 4 42 theme cytolytic 712:720 arg1 activity 722:729 their intrinsic cytolytic activity 696:729 their intrinsic cytolytic activity against tumor cells 696:749 Within this study, cytotoxic CD8(+) T cells were selected as carriers based on both their ability to migrate to the tumor and their intrinsic cytolytic activity against tumor cells. 26606450 0 43 theme nanoparticles 62:74 arg1 coupling 38:45 Reversible coupling 27:45 Reversible coupling of lipid-based nanoparticles to cytotoxic T lymphocytes 27:101 Hitchhiking nanoparticles: Reversible coupling of lipid-based nanoparticles to cytotoxic T lymphocytes. 26606450 5 44 theme anti-cancer 869:879 arg1 effect 881:886 the anti-cancer effect 865:886 the anti-cancer effect 865:886 Many anti-cancer nanomedicines require tumor cell internalization to mediate cytosolic drug delivery and enhance the anti-cancer effect. 26606450 10 45 theme CD8 1536:1538 arg1 cells 1545:1549 CD8(+) T cells 1536:1549 CD8(+) T cells 1536:1549 Based on this optimization using liposomes as model NPs, a small interfering RNA (siRNA)-loaded NP was developed that can be coupled to the surface of CD8(+) T cells. 26606450 5 46 theme cell 797:800 arg1 internalization 802:816 tumor cell internalization 791:816 tumor cell internalization 791:816 Many anti-cancer nanomedicines require tumor cell internalization to mediate cytosolic drug delivery and enhance the anti-cancer effect. 26606450 0 47 theme lipid-based 50:60 arg1 nanoparticles 62:74 lipid-based nanoparticles 50:74 lipid-based nanoparticles 50:74 Hitchhiking nanoparticles: Reversible coupling of lipid-based nanoparticles to cytotoxic T lymphocytes. 26606450 6 48 theme reversible 936:945 arg1 attachment 947:956 the reversible attachment 932:956 the reversible attachment of liposomes to the surface of cytotoxic T lymphocytes 932:1011 This proof-of-concept therefore reports on the reversible attachment of liposomes to the surface of cytotoxic T lymphocytes via a reduction sensitive coupling. 26606450 7 49 theme activation 1053:1062 arg1 status 1064:1069 The activation status 1049:1069 The activation status of the T cells 1049:1084 The activation status of the T cells and the liposome composition are shown to strongly influence the loading efficiency. 26606450 2 50 theme Cell-mediated 223:235 arg1 delivery 237:244 Cell-mediated delivery 223:244 Cell-mediated delivery of nanoparticles (NPs) 223:267 Cell-mediated delivery of nanoparticles (NPs) is promising in terms of overcoming several of these barriers based on the tumoritropic migratory properties of particular cell types. 26606450 1 51 theme anti-cancer 139:149 arg1 nanomedicines 151:163 anti-cancer nanomedicines 139:163 anti-cancer nanomedicines 139:163 Following intravenous injection of anti-cancer nanomedicines, many barriers need to be overcome en route to the tumor. 26606450 10 52 theme -loaded 1473:1479 arg1 NP 1481:1482 a small interfering RNA (siRNA)-loaded NP 1442:1482 a small interfering RNA (siRNA)-loaded NP 1442:1482 Based on this optimization using liposomes as model NPs, a small interfering RNA (siRNA)-loaded NP was developed that can be coupled to the surface of CD8(+) T cells. 26606450 10 53 theme model 1431:1435 arg1 liposomes 1418:1426 liposomes 1418:1426 liposomes 1418:1426 Based on this optimization using liposomes as model NPs, a small interfering RNA (siRNA)-loaded NP was developed that can be coupled to the surface of CD8(+) T cells. 26606450 10 53 theme model 1431:1435 arg1 NPs 1437:1439 model NPs 1431:1439 model NPs 1431:1439 Based on this optimization using liposomes as model NPs, a small interfering RNA (siRNA)-loaded NP was developed that can be coupled to the surface of CD8(+) T cells. 26606450 8 54 with cells 1183:1187 arg1 liposomes 1194:1202 liposomes 1194:1202 liposomes 1194:1202 Loading the cells with liposomes does not compromise T cell functionalities like proliferation and cytolytic function. 26606450 1 55 theme nanomedicines 151:163 arg1 injection 126:134 intravenous injection 114:134 intravenous injection of anti-cancer nanomedicines 114:163 Following intravenous injection of anti-cancer nanomedicines, many barriers need to be overcome en route to the tumor. 26606450 2 56 from promising 272:280 arg1 terms 285:289 terms 285:289 terms of overcoming several of these barriers based on the tumoritropic migratory properties of particular cell types 285:401 Cell-mediated delivery of nanoparticles (NPs) is promising in terms of overcoming several of these barriers based on the tumoritropic migratory properties of particular cell types. 26606450 6 57 theme cytotoxic 989:997 arg1 lymphocytes 1001:1011 cytotoxic T lymphocytes 989:1011 cytotoxic T lymphocytes 989:1011 This proof-of-concept therefore reports on the reversible attachment of liposomes to the surface of cytotoxic T lymphocytes via a reduction sensitive coupling. 26606450 2 58 theme barriers 322:329 arg1 several 305:311 several 305:311 several 305:311 Cell-mediated delivery of nanoparticles (NPs) is promising in terms of overcoming several of these barriers based on the tumoritropic migratory properties of particular cell types. 26606450 8 59 theme cell 1226:1229 arg1 functionalities 1231:1245 T cell functionalities 1224:1245 T cell functionalities like proliferation and cytolytic function 1224:1287 Loading the cells with liposomes does not compromise T cell functionalities like proliferation and cytolytic function. 26606450 3 60 theme NP 446:447 arg1 accumulation 449:460 the NP accumulation 442:460 the NP accumulation in the tumor 442:473 This guided transport aims to enhance the NP accumulation in the tumor and moreover enhance the infiltration of regions that are typically inaccessible for free NPs. 26606450 0 61 theme cytotoxic 79:87 arg1 lymphocytes 91:101 cytotoxic T lymphocytes 79:101 cytotoxic T lymphocytes 79:101 Hitchhiking nanoparticles: Reversible coupling of lipid-based nanoparticles to cytotoxic T lymphocytes. 26606450 5 62 theme drug 839:842 arg1 delivery 844:851 cytosolic drug delivery 829:851 cytosolic drug delivery 829:851 Many anti-cancer nanomedicines require tumor cell internalization to mediate cytosolic drug delivery and enhance the anti-cancer effect. 26606450 3 63 theme regions 516:522 arg1 infiltration 500:511 the infiltration 496:511 the infiltration of regions that are typically inaccessible for free NPs 496:567 This guided transport aims to enhance the NP accumulation in the tumor and moreover enhance the infiltration of regions that are typically inaccessible for free NPs. 26606450 2 64 from terms 285:289 arg1 promising 272:280 promising 272:280 promising 272:280 Cell-mediated delivery of nanoparticles (NPs) is promising in terms of overcoming several of these barriers based on the tumoritropic migratory properties of particular cell types. 26606450 5 65 theme anti-cancer 757:767 arg1 nanomedicines 769:781 Many anti-cancer nanomedicines 752:781 Many anti-cancer nanomedicines 752:781 Many anti-cancer nanomedicines require tumor cell internalization to mediate cytosolic drug delivery and enhance the anti-cancer effect. 26606450 4 66 theme CD8 599:601 arg1 carriers 631:638 carriers 631:638 carriers based on both their ability to migrate to the tumor and their intrinsic cytolytic activity against tumor cells 631:749 Within this study, cytotoxic CD8(+) T cells were selected as carriers based on both their ability to migrate to the tumor and their intrinsic cytolytic activity against tumor cells. 26606450 4 66 theme CD8 599:601 arg1 cells 608:612 cytotoxic CD8(+) T cells 589:612 cytotoxic CD8(+) T cells 589:612 Within this study, cytotoxic CD8(+) T cells were selected as carriers based on both their ability to migrate to the tumor and their intrinsic cytolytic activity against tumor cells. 26606450 6 67 theme sensitive 1029:1037 arg1 coupling 1039:1046 a reduction sensitive coupling 1017:1046 a reduction sensitive coupling 1017:1046 This proof-of-concept therefore reports on the reversible attachment of liposomes to the surface of cytotoxic T lymphocytes via a reduction sensitive coupling. 24576416 12 0 theme chronic 1693:1699 arg1 inflammation 1711:1722 chronic low-grade inflammation 1693:1722 chronic low-grade inflammation 1693:1722 Based on the suppressed MNC-derived cytokine responses suggestive of LPS tolerance, chronic low-grade inflammation may be more profound in obese women with PCOS. 24576416 10 1 theme absolute 1400:1407 arg1 change 1409:1414 The absolute change 1396:1414 The absolute change in plasma IL-6 1396:1429 The absolute change in plasma IL-6 correlated positively with testosterone. 24576416 11 2 theme proatherogenic 1516:1529 arg1 inflammation 1531:1542 proatherogenic inflammation 1516:1542 proatherogenic inflammation in PCOS 1516:1550 We conclude that glucose ingestion promotes proatherogenic inflammation in PCOS with a systemic response that is independent of obesity. 24576416 2 3 theme inflammation 354:365 arg1 markers 328:334 markers 328:334 markers of proatherogenic inflammation in the mononuclear cells (MNC) and plasma of women with PCOS 328:426 We examined the effect of glucose ingestion and lipopolysaccharide (LPS) on markers of proatherogenic inflammation in the mononuclear cells (MNC) and plasma of women with PCOS. 24576416 11 4 theme systemic 1559:1566 arg1 independent 1585:1595 independent 1585:1595 independent 1585:1595 We conclude that glucose ingestion promotes proatherogenic inflammation in PCOS with a systemic response that is independent of obesity. 24576416 11 4 theme systemic 1559:1566 arg1 response 1568:1575 a systemic response 1557:1575 a systemic response that is independent of obesity 1557:1606 We conclude that glucose ingestion promotes proatherogenic inflammation in PCOS with a systemic response that is independent of obesity. 24576416 2 5 theme ingestion 286:294 arg1 effect 268:273 the effect 264:273 the effect of glucose ingestion and lipopolysaccharide (LPS) on markers of proatherogenic inflammation in the mononuclear cells (MNC) and plasma of women with PCOS 264:426 We examined the effect of glucose ingestion and lipopolysaccharide (LPS) on markers of proatherogenic inflammation in the mononuclear cells (MNC) and plasma of women with PCOS. 24576416 4 6 theme soluble 716:722 arg1 sVCAM-1 754:760 sVCAM-1 754:760 sVCAM-1 754:760 Interleukin-6 (IL-6) and interleukin-1β (IL-1β) release from MNC cultured in the presence of LPS and plasma IL-6, C-reactive protein (CRP), and soluble vascular adhesion molecule-1 (sVCAM-1) were measured from blood samples drawn while fasting and 2h after glucose ingestion. 24576416 4 6 theme soluble 716:722 arg1 molecule-1 742:751 soluble vascular adhesion molecule-1 716:751 soluble vascular adhesion molecule-1 (sVCAM-1) 716:761 Interleukin-6 (IL-6) and interleukin-1β (IL-1β) release from MNC cultured in the presence of LPS and plasma IL-6, C-reactive protein (CRP), and soluble vascular adhesion molecule-1 (sVCAM-1) were measured from blood samples drawn while fasting and 2h after glucose ingestion. 24576416 1 7 theme low-grade 182:190 arg1 inflammation 192:203 chronic low-grade inflammation 174:203 chronic low-grade inflammation 174:203 Women with polycystic ovary syndrome (PCOS) have chronic low-grade inflammation, which can increase the risk of atherogenesis. 24576416 4 8 theme adhesion 733:740 arg1 sVCAM-1 754:760 sVCAM-1 754:760 sVCAM-1 754:760 Interleukin-6 (IL-6) and interleukin-1β (IL-1β) release from MNC cultured in the presence of LPS and plasma IL-6, C-reactive protein (CRP), and soluble vascular adhesion molecule-1 (sVCAM-1) were measured from blood samples drawn while fasting and 2h after glucose ingestion. 24576416 4 8 theme adhesion 733:740 arg1 molecule-1 742:751 soluble vascular adhesion molecule-1 716:751 soluble vascular adhesion molecule-1 (sVCAM-1) 716:761 Interleukin-6 (IL-6) and interleukin-1β (IL-1β) release from MNC cultured in the presence of LPS and plasma IL-6, C-reactive protein (CRP), and soluble vascular adhesion molecule-1 (sVCAM-1) were measured from blood samples drawn while fasting and 2h after glucose ingestion. 24576416 2 9 from inflammation 354:365 arg1 MNC 393:395 MNC 393:395 MNC 393:395 We examined the effect of glucose ingestion and lipopolysaccharide (LPS) on markers of proatherogenic inflammation in the mononuclear cells (MNC) and plasma of women with PCOS. 24576416 2 9 from inflammation 354:365 arg1 plasma 402:407 plasma 402:407 plasma of women with PCOS 402:426 We examined the effect of glucose ingestion and lipopolysaccharide (LPS) on markers of proatherogenic inflammation in the mononuclear cells (MNC) and plasma of women with PCOS. 24576416 2 9 from inflammation 354:365 arg1 cells 386:390 the mononuclear cells 370:390 the mononuclear cells (MNC) 370:396 We examined the effect of glucose ingestion and lipopolysaccharide (LPS) on markers of proatherogenic inflammation in the mononuclear cells (MNC) and plasma of women with PCOS. 24576416 6 10 theme glucose 1023:1029 arg1 ingestion 1031:1039 glucose ingestion 1023:1039 glucose ingestion 1023:1039 Lean women with PCOS and obese controls failed to suppress LPS-stimulated IL-6 and IL-1β release from MNC after glucose ingestion. 24576416 9 11 theme plasma 1322:1327 arg1 IL-6 1329:1332 Fasting plasma IL-6 1314:1332 Fasting plasma IL-6 1314:1332 Fasting plasma IL-6 and CRP correlated positively with percentage of truncal fat. 24576416 12 12 theme MNC-derived 1633:1643 arg1 responses 1654:1662 the suppressed MNC-derived cytokine responses 1618:1662 the suppressed MNC-derived cytokine responses suggestive of LPS tolerance 1618:1690 Based on the suppressed MNC-derived cytokine responses suggestive of LPS tolerance, chronic low-grade inflammation may be more profound in obese women with PCOS. 24576416 7 13 link MNC-derived 1094:1104 arg1 cytokines 1106:1114 these MNC-derived cytokines 1088:1114 these MNC-derived cytokines 1088:1114 In contrast, obese women with PCOS suppressed these MNC-derived cytokines under the same conditions. 24576416 1 14 theme polycystic 136:145 arg1 PCOS 163:166 PCOS 163:166 PCOS 163:166 Women with polycystic ovary syndrome (PCOS) have chronic low-grade inflammation, which can increase the risk of atherogenesis. 24576416 1 14 theme polycystic 136:145 arg1 syndrome 153:160 polycystic ovary syndrome 136:160 polycystic ovary syndrome (PCOS) 136:167 Women with polycystic ovary syndrome (PCOS) have chronic low-grade inflammation, which can increase the risk of atherogenesis. 24576416 3 15 theme 3-h 532:534 arg1 OGTT 565:568 OGTT 565:568 OGTT 565:568 Sixteen women with PCOS (8 lean, 8 obese) and 15 weight-matched controls (8 lean, 7 obese) underwent a 3-h oral glucose tolerance test (OGTT). 24576416 3 15 theme 3-h 532:534 arg1 test 559:562 a 3-h oral glucose tolerance test 530:562 a 3-h oral glucose tolerance test (OGTT) 530:569 Sixteen women with PCOS (8 lean, 8 obese) and 15 weight-matched controls (8 lean, 7 obese) underwent a 3-h oral glucose tolerance test (OGTT). 24576416 7 16 with women 1061:1065 arg1 PCOS 1072:1075 PCOS 1072:1075 PCOS 1072:1075 In contrast, obese women with PCOS suppressed these MNC-derived cytokines under the same conditions. 24576416 8 17 theme glucose 1158:1164 arg1 ingestion 1166:1174 glucose ingestion 1158:1174 glucose ingestion 1158:1174 In response to glucose ingestion, plasma IL-6 and sVCAM-1 increased and CRP suppression was attenuated in both PCOS groups and obese controls compared with lean controls. 24576416 3 18 dep controls 493:500 arg1 8 503:503 8 503:503 8 503:503 Sixteen women with PCOS (8 lean, 8 obese) and 15 weight-matched controls (8 lean, 7 obese) underwent a 3-h oral glucose tolerance test (OGTT). 24576416 12 19 from profound 1736:1743 arg1 women 1754:1758 obese women 1748:1758 obese women with PCOS 1748:1768 Based on the suppressed MNC-derived cytokine responses suggestive of LPS tolerance, chronic low-grade inflammation may be more profound in obese women with PCOS. 24576416 4 20 theme blood 782:786 arg1 samples 788:794 blood samples 782:794 blood samples drawn while fasting and 2h after glucose ingestion 782:845 Interleukin-6 (IL-6) and interleukin-1β (IL-1β) release from MNC cultured in the presence of LPS and plasma IL-6, C-reactive protein (CRP), and soluble vascular adhesion molecule-1 (sVCAM-1) were measured from blood samples drawn while fasting and 2h after glucose ingestion. 24576416 4 21 theme interleukin-1β 597:610 arg1 release 620:626 interleukin-1β (IL-1β) release 597:626 interleukin-1β (IL-1β) release from MNC cultured in the presence of LPS and plasma IL-6, C-reactive protein (CRP), and soluble vascular adhesion molecule-1 (sVCAM-1) 597:761 Interleukin-6 (IL-6) and interleukin-1β (IL-1β) release from MNC cultured in the presence of LPS and plasma IL-6, C-reactive protein (CRP), and soluble vascular adhesion molecule-1 (sVCAM-1) were measured from blood samples drawn while fasting and 2h after glucose ingestion. 24576416 7 22 theme MNC-derived 1094:1104 arg1 cytokines 1106:1114 these MNC-derived cytokines 1088:1114 these MNC-derived cytokines 1088:1114 In contrast, obese women with PCOS suppressed these MNC-derived cytokines under the same conditions. 24576416 3 23 theme glucose 541:547 arg1 OGTT 565:568 OGTT 565:568 OGTT 565:568 Sixteen women with PCOS (8 lean, 8 obese) and 15 weight-matched controls (8 lean, 7 obese) underwent a 3-h oral glucose tolerance test (OGTT). 24576416 3 23 theme glucose 541:547 arg1 test 559:562 a 3-h oral glucose tolerance test 530:562 a 3-h oral glucose tolerance test (OGTT) 530:569 Sixteen women with PCOS (8 lean, 8 obese) and 15 weight-matched controls (8 lean, 7 obese) underwent a 3-h oral glucose tolerance test (OGTT). 24576416 9 24 theme fat 1391:1393 arg1 percentage 1369:1378 percentage 1369:1378 percentage of truncal fat 1369:1393 Fasting plasma IL-6 and CRP correlated positively with percentage of truncal fat. 24576416 4 25 theme IL-1β 613:617 arg1 release 620:626 interleukin-1β (IL-1β) release 597:626 interleukin-1β (IL-1β) release from MNC cultured in the presence of LPS and plasma IL-6, C-reactive protein (CRP), and soluble vascular adhesion molecule-1 (sVCAM-1) 597:761 Interleukin-6 (IL-6) and interleukin-1β (IL-1β) release from MNC cultured in the presence of LPS and plasma IL-6, C-reactive protein (CRP), and soluble vascular adhesion molecule-1 (sVCAM-1) were measured from blood samples drawn while fasting and 2h after glucose ingestion. 24576416 1 26 contain have 169:172 arg2 inflammation 192:203 chronic low-grade inflammation 174:203 chronic low-grade inflammation 174:203 Women with polycystic ovary syndrome (PCOS) have chronic low-grade inflammation, which can increase the risk of atherogenesis. 24576416 1 26 contain have 169:172 arg1 Women 125:129 Women 125:129 Women with polycystic ovary syndrome (PCOS) 125:167 Women with polycystic ovary syndrome (PCOS) have chronic low-grade inflammation, which can increase the risk of atherogenesis. 24576416 4 27 theme LPS 665:667 arg1 presence 653:660 the presence 649:660 the presence of LPS and plasma IL-6, C-reactive protein (CRP), and soluble vascular adhesion molecule-1 (sVCAM-1) 649:761 Interleukin-6 (IL-6) and interleukin-1β (IL-1β) release from MNC cultured in the presence of LPS and plasma IL-6, C-reactive protein (CRP), and soluble vascular adhesion molecule-1 (sVCAM-1) were measured from blood samples drawn while fasting and 2h after glucose ingestion. 24576416 0 28 theme ovary 109:113 arg1 syndrome 115:122 polycystic ovary syndrome 98:122 polycystic ovary syndrome 98:122 Glucose and lipopolysaccharide regulate proatherogenic cytokine release from mononuclear cells in polycystic ovary syndrome. 24576416 3 29 dep lean 456:459 arg1 obese 464:468 obese 464:468 obese 464:468 Sixteen women with PCOS (8 lean, 8 obese) and 15 weight-matched controls (8 lean, 7 obese) underwent a 3-h oral glucose tolerance test (OGTT). 24576416 4 30 theme glucose 829:835 arg1 ingestion 837:845 glucose ingestion 829:845 glucose ingestion 829:845 Interleukin-6 (IL-6) and interleukin-1β (IL-1β) release from MNC cultured in the presence of LPS and plasma IL-6, C-reactive protein (CRP), and soluble vascular adhesion molecule-1 (sVCAM-1) were measured from blood samples drawn while fasting and 2h after glucose ingestion. 24576416 4 31 theme plasma 673:678 arg1 IL-6 680:683 plasma IL-6 673:683 plasma IL-6 673:683 Interleukin-6 (IL-6) and interleukin-1β (IL-1β) release from MNC cultured in the presence of LPS and plasma IL-6, C-reactive protein (CRP), and soluble vascular adhesion molecule-1 (sVCAM-1) were measured from blood samples drawn while fasting and 2h after glucose ingestion. 24576416 7 32 theme obese 1055:1059 arg1 women 1061:1065 obese women 1055:1065 obese women with PCOS 1055:1075 In contrast, obese women with PCOS suppressed these MNC-derived cytokines under the same conditions. 24576416 6 33 theme obese 936:940 arg1 controls 942:949 obese controls 936:949 obese controls 936:949 Lean women with PCOS and obese controls failed to suppress LPS-stimulated IL-6 and IL-1β release from MNC after glucose ingestion. 24576416 13 34 theme Excess 1771:1776 arg1 adiposity 1788:1796 adiposity 1788:1796 adiposity 1788:1796 Excess abdominal adiposity and hyperandrogenism may contribute to atherogenesis in PCOS. 24576416 2 35 theme women 412:416 arg1 MNC 393:395 MNC 393:395 MNC 393:395 We examined the effect of glucose ingestion and lipopolysaccharide (LPS) on markers of proatherogenic inflammation in the mononuclear cells (MNC) and plasma of women with PCOS. 24576416 2 35 theme women 412:416 arg1 plasma 402:407 plasma 402:407 plasma of women with PCOS 402:426 We examined the effect of glucose ingestion and lipopolysaccharide (LPS) on markers of proatherogenic inflammation in the mononuclear cells (MNC) and plasma of women with PCOS. 24576416 2 35 theme women 412:416 arg1 cells 386:390 the mononuclear cells 370:390 the mononuclear cells (MNC) 370:396 We examined the effect of glucose ingestion and lipopolysaccharide (LPS) on markers of proatherogenic inflammation in the mononuclear cells (MNC) and plasma of women with PCOS. 24576416 3 36 theme weight-matched 478:491 arg1 controls 493:500 15 weight-matched controls 475:500 15 weight-matched controls (8 lean, 7 obese) 475:518 Sixteen women with PCOS (8 lean, 8 obese) and 15 weight-matched controls (8 lean, 7 obese) underwent a 3-h oral glucose tolerance test (OGTT). 24576416 10 37 from change 1409:1414 arg1 IL-6 1426:1429 plasma IL-6 1419:1429 plasma IL-6 1419:1429 The absolute change in plasma IL-6 correlated positively with testosterone. 24576416 2 38 from effect 268:273 arg1 markers 328:334 markers 328:334 markers of proatherogenic inflammation in the mononuclear cells (MNC) and plasma of women with PCOS 328:426 We examined the effect of glucose ingestion and lipopolysaccharide (LPS) on markers of proatherogenic inflammation in the mononuclear cells (MNC) and plasma of women with PCOS. 24576416 9 39 theme truncal 1383:1389 arg1 fat 1391:1393 truncal fat 1383:1393 truncal fat 1383:1393 Fasting plasma IL-6 and CRP correlated positively with percentage of truncal fat. 24576416 0 40 theme proatherogenic 40:53 arg1 release 64:70 proatherogenic cytokine release 40:70 proatherogenic cytokine release from mononuclear cells in polycystic ovary syndrome 40:122 Glucose and lipopolysaccharide regulate proatherogenic cytokine release from mononuclear cells in polycystic ovary syndrome. 24576416 3 41 with controls 493:500 arg1 PCOS 448:451 PCOS 448:451 PCOS 448:451 Sixteen women with PCOS (8 lean, 8 obese) and 15 weight-matched controls (8 lean, 7 obese) underwent a 3-h oral glucose tolerance test (OGTT). 24576416 0 42 theme mononuclear 77:87 arg1 cells 89:93 mononuclear cells 77:93 mononuclear cells in polycystic ovary syndrome 77:122 Glucose and lipopolysaccharide regulate proatherogenic cytokine release from mononuclear cells in polycystic ovary syndrome. 24576416 8 43 theme obese 1270:1274 arg1 controls 1276:1283 obese controls 1270:1283 obese controls 1270:1283 In response to glucose ingestion, plasma IL-6 and sVCAM-1 increased and CRP suppression was attenuated in both PCOS groups and obese controls compared with lean controls. 24576416 2 44 theme proatherogenic 339:352 arg1 inflammation 354:365 proatherogenic inflammation 339:365 proatherogenic inflammation in the mononuclear cells (MNC) and plasma of women with PCOS 339:426 We examined the effect of glucose ingestion and lipopolysaccharide (LPS) on markers of proatherogenic inflammation in the mononuclear cells (MNC) and plasma of women with PCOS. 24576416 6 45 theme IL-1β 994:998 arg1 release 1000:1006 LPS-stimulated IL-6 and IL-1β release 970:1006 release 1000:1006 Lean women with PCOS and obese controls failed to suppress LPS-stimulated IL-6 and IL-1β release from MNC after glucose ingestion. 24576416 12 46 theme obese 1748:1752 arg1 women 1754:1758 obese women 1748:1758 obese women with PCOS 1748:1768 Based on the suppressed MNC-derived cytokine responses suggestive of LPS tolerance, chronic low-grade inflammation may be more profound in obese women with PCOS. 24576416 8 47 dep ingestion 1166:1174 arg1 response 1146:1153 response 1146:1153 response 1146:1153 In response to glucose ingestion, plasma IL-6 and sVCAM-1 increased and CRP suppression was attenuated in both PCOS groups and obese controls compared with lean controls. 24576416 2 48 from plasma 402:407 arg1 markers 328:334 markers 328:334 markers of proatherogenic inflammation in the mononuclear cells (MNC) and plasma of women with PCOS 328:426 We examined the effect of glucose ingestion and lipopolysaccharide (LPS) on markers of proatherogenic inflammation in the mononuclear cells (MNC) and plasma of women with PCOS. 24576416 10 49 theme plasma 1419:1424 arg1 IL-6 1426:1429 plasma IL-6 1419:1429 plasma IL-6 1419:1429 The absolute change in plasma IL-6 correlated positively with testosterone. 24576416 8 50 theme lean 1299:1302 arg1 controls 1304:1311 lean controls 1299:1311 lean controls 1299:1311 In response to glucose ingestion, plasma IL-6 and sVCAM-1 increased and CRP suppression was attenuated in both PCOS groups and obese controls compared with lean controls. 24576416 2 51 theme mononuclear 374:384 arg1 MNC 393:395 MNC 393:395 MNC 393:395 We examined the effect of glucose ingestion and lipopolysaccharide (LPS) on markers of proatherogenic inflammation in the mononuclear cells (MNC) and plasma of women with PCOS. 24576416 2 51 theme mononuclear 374:384 arg1 cells 386:390 the mononuclear cells 370:390 the mononuclear cells (MNC) 370:396 We examined the effect of glucose ingestion and lipopolysaccharide (LPS) on markers of proatherogenic inflammation in the mononuclear cells (MNC) and plasma of women with PCOS. 24576416 1 52 theme atherogenesis 237:249 arg1 risk 229:232 the risk 225:232 the risk of atherogenesis 225:249 Women with polycystic ovary syndrome (PCOS) have chronic low-grade inflammation, which can increase the risk of atherogenesis. 24576416 5 53 theme dual-energy 876:886 arg1 DEXA 904:907 DEXA 904:907 DEXA 904:907 Truncal fat was measured by dual-energy absorptiometry (DEXA). 24576416 5 53 theme dual-energy 876:886 arg1 absorptiometry 888:901 dual-energy absorptiometry 876:901 dual-energy absorptiometry (DEXA) 876:908 Truncal fat was measured by dual-energy absorptiometry (DEXA). 24576416 12 54 theme low-grade 1701:1709 arg1 inflammation 1711:1722 chronic low-grade inflammation 1693:1722 chronic low-grade inflammation 1693:1722 Based on the suppressed MNC-derived cytokine responses suggestive of LPS tolerance, chronic low-grade inflammation may be more profound in obese women with PCOS. 24576416 7 55 theme same 1126:1129 arg1 conditions 1131:1140 the same conditions 1122:1140 the same conditions 1122:1140 In contrast, obese women with PCOS suppressed these MNC-derived cytokines under the same conditions. 24576416 11 56 theme glucose 1489:1495 arg1 ingestion 1497:1505 glucose ingestion 1489:1505 glucose ingestion 1489:1505 We conclude that glucose ingestion promotes proatherogenic inflammation in PCOS with a systemic response that is independent of obesity. 24576416 12 57 with women 1754:1758 arg1 PCOS 1765:1768 PCOS 1765:1768 PCOS 1765:1768 Based on the suppressed MNC-derived cytokine responses suggestive of LPS tolerance, chronic low-grade inflammation may be more profound in obese women with PCOS. 24576416 4 58 theme molecule-1 742:751 arg1 presence 653:660 the presence 649:660 the presence of LPS and plasma IL-6, C-reactive protein (CRP), and soluble vascular adhesion molecule-1 (sVCAM-1) 649:761 Interleukin-6 (IL-6) and interleukin-1β (IL-1β) release from MNC cultured in the presence of LPS and plasma IL-6, C-reactive protein (CRP), and soluble vascular adhesion molecule-1 (sVCAM-1) were measured from blood samples drawn while fasting and 2h after glucose ingestion. 24576416 2 59 from markers 328:334 arg1 MNC 393:395 MNC 393:395 MNC 393:395 We examined the effect of glucose ingestion and lipopolysaccharide (LPS) on markers of proatherogenic inflammation in the mononuclear cells (MNC) and plasma of women with PCOS. 24576416 2 59 from markers 328:334 arg1 plasma 402:407 plasma 402:407 plasma of women with PCOS 402:426 We examined the effect of glucose ingestion and lipopolysaccharide (LPS) on markers of proatherogenic inflammation in the mononuclear cells (MNC) and plasma of women with PCOS. 24576416 2 59 from markers 328:334 arg1 cells 386:390 the mononuclear cells 370:390 the mononuclear cells (MNC) 370:396 We examined the effect of glucose ingestion and lipopolysaccharide (LPS) on markers of proatherogenic inflammation in the mononuclear cells (MNC) and plasma of women with PCOS. 24576416 12 60 theme LPS 1678:1680 arg1 tolerance 1682:1690 LPS tolerance 1678:1690 LPS tolerance 1678:1690 Based on the suppressed MNC-derived cytokine responses suggestive of LPS tolerance, chronic low-grade inflammation may be more profound in obese women with PCOS. 24576416 2 61 theme glucose 278:284 arg1 ingestion 286:294 glucose ingestion 278:294 glucose ingestion 278:294 We examined the effect of glucose ingestion and lipopolysaccharide (LPS) on markers of proatherogenic inflammation in the mononuclear cells (MNC) and plasma of women with PCOS. 24576416 1 62 theme chronic 174:180 arg1 inflammation 192:203 chronic low-grade inflammation 174:203 chronic low-grade inflammation 174:203 Women with polycystic ovary syndrome (PCOS) have chronic low-grade inflammation, which can increase the risk of atherogenesis. 24576416 2 63 with women 412:416 arg1 PCOS 423:426 PCOS 423:426 PCOS 423:426 We examined the effect of glucose ingestion and lipopolysaccharide (LPS) on markers of proatherogenic inflammation in the mononuclear cells (MNC) and plasma of women with PCOS. 24576416 12 64 theme suppressed 1622:1631 arg1 responses 1654:1662 the suppressed MNC-derived cytokine responses 1618:1662 the suppressed MNC-derived cytokine responses suggestive of LPS tolerance 1618:1690 Based on the suppressed MNC-derived cytokine responses suggestive of LPS tolerance, chronic low-grade inflammation may be more profound in obese women with PCOS. 24576416 9 65 theme Fasting 1314:1320 arg1 IL-6 1329:1332 Fasting plasma IL-6 1314:1332 Fasting plasma IL-6 1314:1332 Fasting plasma IL-6 and CRP correlated positively with percentage of truncal fat. 24576416 1 66 with Women 125:129 arg1 PCOS 163:166 PCOS 163:166 PCOS 163:166 Women with polycystic ovary syndrome (PCOS) have chronic low-grade inflammation, which can increase the risk of atherogenesis. 24576416 1 66 with Women 125:129 arg1 syndrome 153:160 polycystic ovary syndrome 136:160 polycystic ovary syndrome (PCOS) 136:167 Women with polycystic ovary syndrome (PCOS) have chronic low-grade inflammation, which can increase the risk of atherogenesis. 24576416 4 67 theme vascular 724:731 arg1 sVCAM-1 754:760 sVCAM-1 754:760 sVCAM-1 754:760 Interleukin-6 (IL-6) and interleukin-1β (IL-1β) release from MNC cultured in the presence of LPS and plasma IL-6, C-reactive protein (CRP), and soluble vascular adhesion molecule-1 (sVCAM-1) were measured from blood samples drawn while fasting and 2h after glucose ingestion. 24576416 4 67 theme vascular 724:731 arg1 molecule-1 742:751 soluble vascular adhesion molecule-1 716:751 soluble vascular adhesion molecule-1 (sVCAM-1) 716:761 Interleukin-6 (IL-6) and interleukin-1β (IL-1β) release from MNC cultured in the presence of LPS and plasma IL-6, C-reactive protein (CRP), and soluble vascular adhesion molecule-1 (sVCAM-1) were measured from blood samples drawn while fasting and 2h after glucose ingestion. 24576416 12 68 theme cytokine 1645:1652 arg1 responses 1654:1662 the suppressed MNC-derived cytokine responses 1618:1662 the suppressed MNC-derived cytokine responses suggestive of LPS tolerance 1618:1690 Based on the suppressed MNC-derived cytokine responses suggestive of LPS tolerance, chronic low-grade inflammation may be more profound in obese women with PCOS. 24576416 3 69 with women 437:441 arg1 PCOS 448:451 PCOS 448:451 PCOS 448:451 Sixteen women with PCOS (8 lean, 8 obese) and 15 weight-matched controls (8 lean, 7 obese) underwent a 3-h oral glucose tolerance test (OGTT). 24576416 12 70 from women 1754:1758 arg1 profound 1736:1743 profound 1736:1743 profound 1736:1743 Based on the suppressed MNC-derived cytokine responses suggestive of LPS tolerance, chronic low-grade inflammation may be more profound in obese women with PCOS. 24576416 0 71 from cells 89:93 arg1 syndrome 115:122 polycystic ovary syndrome 98:122 polycystic ovary syndrome 98:122 Glucose and lipopolysaccharide regulate proatherogenic cytokine release from mononuclear cells in polycystic ovary syndrome. 24576416 0 71 from cells 89:93 arg1 release 64:70 proatherogenic cytokine release 40:70 proatherogenic cytokine release from mononuclear cells in polycystic ovary syndrome 40:122 Glucose and lipopolysaccharide regulate proatherogenic cytokine release from mononuclear cells in polycystic ovary syndrome. 24576416 3 72 theme tolerance 549:557 arg1 OGTT 565:568 OGTT 565:568 OGTT 565:568 Sixteen women with PCOS (8 lean, 8 obese) and 15 weight-matched controls (8 lean, 7 obese) underwent a 3-h oral glucose tolerance test (OGTT). 24576416 3 72 theme tolerance 549:557 arg1 test 559:562 a 3-h oral glucose tolerance test 530:562 a 3-h oral glucose tolerance test (OGTT) 530:569 Sixteen women with PCOS (8 lean, 8 obese) and 15 weight-matched controls (8 lean, 7 obese) underwent a 3-h oral glucose tolerance test (OGTT). 24576416 1 73 theme ovary 147:151 arg1 PCOS 163:166 PCOS 163:166 PCOS 163:166 Women with polycystic ovary syndrome (PCOS) have chronic low-grade inflammation, which can increase the risk of atherogenesis. 24576416 1 73 theme ovary 147:151 arg1 syndrome 153:160 polycystic ovary syndrome 136:160 polycystic ovary syndrome (PCOS) 136:167 Women with polycystic ovary syndrome (PCOS) have chronic low-grade inflammation, which can increase the risk of atherogenesis. 24576416 3 74 theme oral 536:539 arg1 OGTT 565:568 OGTT 565:568 OGTT 565:568 Sixteen women with PCOS (8 lean, 8 obese) and 15 weight-matched controls (8 lean, 7 obese) underwent a 3-h oral glucose tolerance test (OGTT). 24576416 3 74 theme oral 536:539 arg1 test 559:562 a 3-h oral glucose tolerance test 530:562 a 3-h oral glucose tolerance test (OGTT) 530:569 Sixteen women with PCOS (8 lean, 8 obese) and 15 weight-matched controls (8 lean, 7 obese) underwent a 3-h oral glucose tolerance test (OGTT). 24576416 3 75 dep lean 505:508 arg1 obese 513:517 obese 513:517 obese 513:517 Sixteen women with PCOS (8 lean, 8 obese) and 15 weight-matched controls (8 lean, 7 obese) underwent a 3-h oral glucose tolerance test (OGTT). 24576416 8 76 theme plasma 1177:1182 arg1 IL-6 1184:1187 plasma IL-6 1177:1187 plasma IL-6 1177:1187 In response to glucose ingestion, plasma IL-6 and sVCAM-1 increased and CRP suppression was attenuated in both PCOS groups and obese controls compared with lean controls. 24576416 13 77 theme abdominal 1778:1786 arg1 adiposity 1788:1796 adiposity 1788:1796 adiposity 1788:1796 Excess abdominal adiposity and hyperandrogenism may contribute to atherogenesis in PCOS. 24576416 12 78 link MNC-derived 1633:1643 arg1 responses 1654:1662 the suppressed MNC-derived cytokine responses 1618:1662 the suppressed MNC-derived cytokine responses suggestive of LPS tolerance 1618:1690 Based on the suppressed MNC-derived cytokine responses suggestive of LPS tolerance, chronic low-grade inflammation may be more profound in obese women with PCOS. 24576416 0 79 theme polycystic 98:107 arg1 syndrome 115:122 polycystic ovary syndrome 98:122 polycystic ovary syndrome 98:122 Glucose and lipopolysaccharide regulate proatherogenic cytokine release from mononuclear cells in polycystic ovary syndrome. 24576416 2 80 theme lipopolysaccharide 300:317 arg1 effect 268:273 the effect 264:273 the effect of glucose ingestion and lipopolysaccharide (LPS) on markers of proatherogenic inflammation in the mononuclear cells (MNC) and plasma of women with PCOS 264:426 We examined the effect of glucose ingestion and lipopolysaccharide (LPS) on markers of proatherogenic inflammation in the mononuclear cells (MNC) and plasma of women with PCOS. 24576416 5 81 theme Truncal 848:854 arg1 fat 856:858 Truncal fat 848:858 Truncal fat 848:858 Truncal fat was measured by dual-energy absorptiometry (DEXA). 24576416 8 82 theme CRP 1215:1217 arg1 suppression 1219:1229 CRP suppression 1215:1229 CRP suppression 1215:1229 In response to glucose ingestion, plasma IL-6 and sVCAM-1 increased and CRP suppression was attenuated in both PCOS groups and obese controls compared with lean controls. 24576416 4 83 theme protein 697:703 arg1 presence 653:660 the presence 649:660 the presence of LPS and plasma IL-6, C-reactive protein (CRP), and soluble vascular adhesion molecule-1 (sVCAM-1) 649:761 Interleukin-6 (IL-6) and interleukin-1β (IL-1β) release from MNC cultured in the presence of LPS and plasma IL-6, C-reactive protein (CRP), and soluble vascular adhesion molecule-1 (sVCAM-1) were measured from blood samples drawn while fasting and 2h after glucose ingestion. 24576416 0 84 theme cytokine 55:62 arg1 release 64:70 proatherogenic cytokine release 40:70 proatherogenic cytokine release from mononuclear cells in polycystic ovary syndrome 40:122 Glucose and lipopolysaccharide regulate proatherogenic cytokine release from mononuclear cells in polycystic ovary syndrome. 24576416 6 85 theme Lean 911:914 arg1 women 916:920 Lean women 911:920 Lean women with PCOS and obese controls 911:949 Lean women with PCOS and obese controls failed to suppress LPS-stimulated IL-6 and IL-1β release from MNC after glucose ingestion. 24576416 11 86 from inflammation 1531:1542 arg1 PCOS 1547:1550 PCOS 1547:1550 PCOS 1547:1550 We conclude that glucose ingestion promotes proatherogenic inflammation in PCOS with a systemic response that is independent of obesity. 24576416 8 87 theme PCOS 1254:1257 arg1 groups 1259:1264 PCOS groups 1254:1264 PCOS groups 1254:1264 In response to glucose ingestion, plasma IL-6 and sVCAM-1 increased and CRP suppression was attenuated in both PCOS groups and obese controls compared with lean controls. 24576416 2 88 from cells 386:390 arg1 markers 328:334 markers 328:334 markers of proatherogenic inflammation in the mononuclear cells (MNC) and plasma of women with PCOS 328:426 We examined the effect of glucose ingestion and lipopolysaccharide (LPS) on markers of proatherogenic inflammation in the mononuclear cells (MNC) and plasma of women with PCOS. 24576416 4 89 from MNC 633:635 arg1 release 620:626 interleukin-1β (IL-1β) release 597:626 interleukin-1β (IL-1β) release from MNC cultured in the presence of LPS and plasma IL-6, C-reactive protein (CRP), and soluble vascular adhesion molecule-1 (sVCAM-1) 597:761 Interleukin-6 (IL-6) and interleukin-1β (IL-1β) release from MNC cultured in the presence of LPS and plasma IL-6, C-reactive protein (CRP), and soluble vascular adhesion molecule-1 (sVCAM-1) were measured from blood samples drawn while fasting and 2h after glucose ingestion. 24576416 4 89 from MNC 633:635 arg1 IL-6 587:590 IL-6 587:590 IL-6 587:590 Interleukin-6 (IL-6) and interleukin-1β (IL-1β) release from MNC cultured in the presence of LPS and plasma IL-6, C-reactive protein (CRP), and soluble vascular adhesion molecule-1 (sVCAM-1) were measured from blood samples drawn while fasting and 2h after glucose ingestion. 24576416 4 89 from MNC 633:635 arg1 Interleukin-6 572:584 Interleukin-6 572:584 Interleukin-6 (IL-6) 572:591 Interleukin-6 (IL-6) and interleukin-1β (IL-1β) release from MNC cultured in the presence of LPS and plasma IL-6, C-reactive protein (CRP), and soluble vascular adhesion molecule-1 (sVCAM-1) were measured from blood samples drawn while fasting and 2h after glucose ingestion. 24576416 3 90 dep women 437:441 arg1 8 454:454 8 454:454 8 454:454 Sixteen women with PCOS (8 lean, 8 obese) and 15 weight-matched controls (8 lean, 7 obese) underwent a 3-h oral glucose tolerance test (OGTT). 24576416 11 91 theme obesity 1600:1606 arg1 independent 1585:1595 independent 1585:1595 independent 1585:1595 We conclude that glucose ingestion promotes proatherogenic inflammation in PCOS with a systemic response that is independent of obesity. 24576416 11 91 theme obesity 1600:1606 arg1 response 1568:1575 a systemic response 1557:1575 a systemic response that is independent of obesity 1557:1606 We conclude that glucose ingestion promotes proatherogenic inflammation in PCOS with a systemic response that is independent of obesity. 24576416 4 92 theme IL-6 680:683 arg1 presence 653:660 the presence 649:660 the presence of LPS and plasma IL-6, C-reactive protein (CRP), and soluble vascular adhesion molecule-1 (sVCAM-1) 649:761 Interleukin-6 (IL-6) and interleukin-1β (IL-1β) release from MNC cultured in the presence of LPS and plasma IL-6, C-reactive protein (CRP), and soluble vascular adhesion molecule-1 (sVCAM-1) were measured from blood samples drawn while fasting and 2h after glucose ingestion. 24576416 6 93 with women 916:920 arg1 PCOS 927:930 PCOS 927:930 PCOS 927:930 Lean women with PCOS and obese controls failed to suppress LPS-stimulated IL-6 and IL-1β release from MNC after glucose ingestion. 24576416 6 93 with women 916:920 arg1 controls 942:949 obese controls 936:949 obese controls 936:949 Lean women with PCOS and obese controls failed to suppress LPS-stimulated IL-6 and IL-1β release from MNC after glucose ingestion. 24576416 12 94 theme tolerance 1682:1690 arg1 suggestive 1664:1673 suggestive 1664:1673 suggestive 1664:1673 Based on the suppressed MNC-derived cytokine responses suggestive of LPS tolerance, chronic low-grade inflammation may be more profound in obese women with PCOS. 24576416 6 95 theme LPS-stimulated 970:983 arg1 IL-6 985:988 LPS-stimulated IL-6 and IL-1β release 970:1006 IL-6 985:988 Lean women with PCOS and obese controls failed to suppress LPS-stimulated IL-6 and IL-1β release from MNC after glucose ingestion. 24576416 4 96 theme C-reactive 686:695 arg1 CRP 706:708 CRP 706:708 CRP 706:708 Interleukin-6 (IL-6) and interleukin-1β (IL-1β) release from MNC cultured in the presence of LPS and plasma IL-6, C-reactive protein (CRP), and soluble vascular adhesion molecule-1 (sVCAM-1) were measured from blood samples drawn while fasting and 2h after glucose ingestion. 24576416 4 96 theme C-reactive 686:695 arg1 protein 697:703 C-reactive protein 686:703 C-reactive protein (CRP) 686:709 Interleukin-6 (IL-6) and interleukin-1β (IL-1β) release from MNC cultured in the presence of LPS and plasma IL-6, C-reactive protein (CRP), and soluble vascular adhesion molecule-1 (sVCAM-1) were measured from blood samples drawn while fasting and 2h after glucose ingestion. 26797224 5 0 theme fibroblastoma 1104:1116 arg1 cells 1118:1122 fibroblastoma cells 1104:1122 fibroblastoma cells 1104:1122 In addition to their use as biomaterials, glycated collagens interact with cells in complex ways and a previous study has already shown the ability of a glycated collagen to redirect fibroblastoma cells from proliferation to differentiation. 26797224 2 1 attach O-linked 244:251 arg3 bridge 275:280 a tetrasaccharide bridge 257:280 a tetrasaccharide bridge to the serine residues of a specific protein core 257:330 At variance with natural proteoglycans, whose glycosaminoglycan chains are always O-linked via a tetrasaccharide bridge to the serine residues of a specific protein core, the present structure consists of chondroitin-6-sulfate chains directly bound to the lysine and hydroxylysine residues of a collagen molecule backbone. 26797224 4 2 theme variables 603:611 arg1 number 593:598 The number 589:598 The number of variables involved (e.g., length and type of the collagen backbone, glycosaminoglycan species, sulfation type and pattern, molecular weight, number and length of side chains, etc.) 589:782 The number of variables involved (e.g., length and type of the collagen backbone, glycosaminoglycan species, sulfation type and pattern, molecular weight, number and length of side chains, etc.) makes possible to conceive an almost endless variety of artificial proteoglycans, each precisely tailored to a specific functional role. 26797224 4 3 theme chains 770:775 arg1 length 755:760 length 755:760 length 755:760 The number of variables involved (e.g., length and type of the collagen backbone, glycosaminoglycan species, sulfation type and pattern, molecular weight, number and length of side chains, etc.) makes possible to conceive an almost endless variety of artificial proteoglycans, each precisely tailored to a specific functional role. 26797224 4 3 theme chains 770:775 arg1 length 629:634 length 629:634 length 629:634 The number of variables involved (e.g., length and type of the collagen backbone, glycosaminoglycan species, sulfation type and pattern, molecular weight, number and length of side chains, etc.) makes possible to conceive an almost endless variety of artificial proteoglycans, each precisely tailored to a specific functional role. 26797224 4 3 theme chains 770:775 arg1 number 744:749 number 744:749 number 744:749 The number of variables involved (e.g., length and type of the collagen backbone, glycosaminoglycan species, sulfation type and pattern, molecular weight, number and length of side chains, etc.) makes possible to conceive an almost endless variety of artificial proteoglycans, each precisely tailored to a specific functional role. 26797224 1 4 theme artificial 80:89 arg1 proteoglycan 105:116 An artificial aggrecan-like proteoglycan 77:116 An artificial aggrecan-like proteoglycan 77:116 An artificial aggrecan-like proteoglycan has been designed and synthesized in vitro. 26797224 4 5 theme side 765:768 arg1 chains 770:775 side chains 765:775 side chains 765:775 The number of variables involved (e.g., length and type of the collagen backbone, glycosaminoglycan species, sulfation type and pattern, molecular weight, number and length of side chains, etc.) makes possible to conceive an almost endless variety of artificial proteoglycans, each precisely tailored to a specific functional role. 26797224 5 6 from cells 996:1000 arg1 ways 1013:1016 complex ways 1005:1016 complex ways 1005:1016 In addition to their use as biomaterials, glycated collagens interact with cells in complex ways and a previous study has already shown the ability of a glycated collagen to redirect fibroblastoma cells from proliferation to differentiation. 26797224 5 7 theme glycated 1074:1081 arg1 collagen 1083:1090 a glycated collagen 1072:1090 a glycated collagen 1072:1090 In addition to their use as biomaterials, glycated collagens interact with cells in complex ways and a previous study has already shown the ability of a glycated collagen to redirect fibroblastoma cells from proliferation to differentiation. 26797224 3 8 theme resulting 489:497 arg1 macromolecule 499:511 The resulting macromolecule 485:511 The resulting macromolecule 485:511 The resulting macromolecule has been characterized by histochemistry, atomic force microscopy and FTIR. 26797224 2 9 theme serine 289:294 arg1 residues 296:303 the serine residues 285:303 the serine residues of a specific protein core 285:330 At variance with natural proteoglycans, whose glycosaminoglycan chains are always O-linked via a tetrasaccharide bridge to the serine residues of a specific protein core, the present structure consists of chondroitin-6-sulfate chains directly bound to the lysine and hydroxylysine residues of a collagen molecule backbone. 26797224 2 9 theme serine 289:294 arg1 core 327:330 a specific protein core 308:330 a specific protein core 308:330 At variance with natural proteoglycans, whose glycosaminoglycan chains are always O-linked via a tetrasaccharide bridge to the serine residues of a specific protein core, the present structure consists of chondroitin-6-sulfate chains directly bound to the lysine and hydroxylysine residues of a collagen molecule backbone. 26797224 4 10 theme glycosaminoglycan 671:687 arg1 length 629:634 length 629:634 length 629:634 The number of variables involved (e.g., length and type of the collagen backbone, glycosaminoglycan species, sulfation type and pattern, molecular weight, number and length of side chains, etc.) makes possible to conceive an almost endless variety of artificial proteoglycans, each precisely tailored to a specific functional role. 26797224 4 10 theme glycosaminoglycan 671:687 arg1 species 689:695 glycosaminoglycan species 671:695 glycosaminoglycan species 671:695 The number of variables involved (e.g., length and type of the collagen backbone, glycosaminoglycan species, sulfation type and pattern, molecular weight, number and length of side chains, etc.) makes possible to conceive an almost endless variety of artificial proteoglycans, each precisely tailored to a specific functional role. 26797224 5 11 theme collagen 1083:1090 arg1 ability 1061:1067 the ability 1057:1067 the ability of a glycated collagen to redirect fibroblastoma cells from proliferation to differentiation 1057:1160 In addition to their use as biomaterials, glycated collagens interact with cells in complex ways and a previous study has already shown the ability of a glycated collagen to redirect fibroblastoma cells from proliferation to differentiation. 26797224 2 12 theme molecule 466:473 arg1 backbone 475:482 a collagen molecule backbone 455:482 a collagen molecule backbone 455:482 At variance with natural proteoglycans, whose glycosaminoglycan chains are always O-linked via a tetrasaccharide bridge to the serine residues of a specific protein core, the present structure consists of chondroitin-6-sulfate chains directly bound to the lysine and hydroxylysine residues of a collagen molecule backbone. 26797224 4 13 theme proteoglycans 851:863 arg1 each 866:869 each 866:869 each 866:869 The number of variables involved (e.g., length and type of the collagen backbone, glycosaminoglycan species, sulfation type and pattern, molecular weight, number and length of side chains, etc.) makes possible to conceive an almost endless variety of artificial proteoglycans, each precisely tailored to a specific functional role. 26797224 4 13 theme proteoglycans 851:863 arg1 variety 829:835 an almost endless variety 811:835 an almost endless variety of artificial proteoglycans, each precisely tailored to a specific functional role 811:918 The number of variables involved (e.g., length and type of the collagen backbone, glycosaminoglycan species, sulfation type and pattern, molecular weight, number and length of side chains, etc.) makes possible to conceive an almost endless variety of artificial proteoglycans, each precisely tailored to a specific functional role. 26797224 4 13 theme proteoglycans 851:863 arg1 proteoglycans 851:863 artificial proteoglycans 840:863 artificial proteoglycans 840:863 The number of variables involved (e.g., length and type of the collagen backbone, glycosaminoglycan species, sulfation type and pattern, molecular weight, number and length of side chains, etc.) makes possible to conceive an almost endless variety of artificial proteoglycans, each precisely tailored to a specific functional role. 26797224 2 14 theme core 327:330 arg1 residues 296:303 the serine residues 285:303 the serine residues of a specific protein core 285:330 At variance with natural proteoglycans, whose glycosaminoglycan chains are always O-linked via a tetrasaccharide bridge to the serine residues of a specific protein core, the present structure consists of chondroitin-6-sulfate chains directly bound to the lysine and hydroxylysine residues of a collagen molecule backbone. 26797224 2 14 theme core 327:330 arg1 core 327:330 a specific protein core 308:330 a specific protein core 308:330 At variance with natural proteoglycans, whose glycosaminoglycan chains are always O-linked via a tetrasaccharide bridge to the serine residues of a specific protein core, the present structure consists of chondroitin-6-sulfate chains directly bound to the lysine and hydroxylysine residues of a collagen molecule backbone. 26797224 2 15 theme collagen 457:464 arg1 backbone 475:482 a collagen molecule backbone 455:482 a collagen molecule backbone 455:482 At variance with natural proteoglycans, whose glycosaminoglycan chains are always O-linked via a tetrasaccharide bridge to the serine residues of a specific protein core, the present structure consists of chondroitin-6-sulfate chains directly bound to the lysine and hydroxylysine residues of a collagen molecule backbone. 26797224 4 16 theme artificial 840:849 arg1 each 866:869 each 866:869 each 866:869 The number of variables involved (e.g., length and type of the collagen backbone, glycosaminoglycan species, sulfation type and pattern, molecular weight, number and length of side chains, etc.) makes possible to conceive an almost endless variety of artificial proteoglycans, each precisely tailored to a specific functional role. 26797224 4 16 theme artificial 840:849 arg1 proteoglycans 851:863 artificial proteoglycans 840:863 artificial proteoglycans 840:863 The number of variables involved (e.g., length and type of the collagen backbone, glycosaminoglycan species, sulfation type and pattern, molecular weight, number and length of side chains, etc.) makes possible to conceive an almost endless variety of artificial proteoglycans, each precisely tailored to a specific functional role. 26797224 2 17 theme protein 319:325 arg1 core 327:330 a specific protein core 308:330 a specific protein core 308:330 At variance with natural proteoglycans, whose glycosaminoglycan chains are always O-linked via a tetrasaccharide bridge to the serine residues of a specific protein core, the present structure consists of chondroitin-6-sulfate chains directly bound to the lysine and hydroxylysine residues of a collagen molecule backbone. 26797224 2 18 theme specific 310:317 arg1 core 327:330 a specific protein core 308:330 a specific protein core 308:330 At variance with natural proteoglycans, whose glycosaminoglycan chains are always O-linked via a tetrasaccharide bridge to the serine residues of a specific protein core, the present structure consists of chondroitin-6-sulfate chains directly bound to the lysine and hydroxylysine residues of a collagen molecule backbone. 26797224 1 19 theme aggrecan-like 91:103 arg1 proteoglycan 105:116 An artificial aggrecan-like proteoglycan 77:116 An artificial aggrecan-like proteoglycan 77:116 An artificial aggrecan-like proteoglycan has been designed and synthesized in vitro. 26797224 3 20 theme force 562:566 arg1 microscopy 568:577 atomic force microscopy 555:577 atomic force microscopy 555:577 The resulting macromolecule has been characterized by histochemistry, atomic force microscopy and FTIR. 26797224 2 21 theme hydroxylysine 429:441 arg1 backbone 475:482 a collagen molecule backbone 455:482 a collagen molecule backbone 455:482 At variance with natural proteoglycans, whose glycosaminoglycan chains are always O-linked via a tetrasaccharide bridge to the serine residues of a specific protein core, the present structure consists of chondroitin-6-sulfate chains directly bound to the lysine and hydroxylysine residues of a collagen molecule backbone. 26797224 2 21 theme hydroxylysine 429:441 arg1 residues 443:450 the lysine and hydroxylysine residues 414:450 residues 443:450 At variance with natural proteoglycans, whose glycosaminoglycan chains are always O-linked via a tetrasaccharide bridge to the serine residues of a specific protein core, the present structure consists of chondroitin-6-sulfate chains directly bound to the lysine and hydroxylysine residues of a collagen molecule backbone. 26797224 2 22 with variance 165:172 arg1 proteoglycans 187:199 natural proteoglycans 179:199 natural proteoglycans 179:199 At variance with natural proteoglycans, whose glycosaminoglycan chains are always O-linked via a tetrasaccharide bridge to the serine residues of a specific protein core, the present structure consists of chondroitin-6-sulfate chains directly bound to the lysine and hydroxylysine residues of a collagen molecule backbone. 26797224 2 23 theme natural 179:185 arg1 proteoglycans 187:199 natural proteoglycans 179:199 natural proteoglycans 179:199 At variance with natural proteoglycans, whose glycosaminoglycan chains are always O-linked via a tetrasaccharide bridge to the serine residues of a specific protein core, the present structure consists of chondroitin-6-sulfate chains directly bound to the lysine and hydroxylysine residues of a collagen molecule backbone. 26797224 5 24 theme complex 1005:1011 arg1 ways 1013:1016 complex ways 1005:1016 complex ways 1005:1016 In addition to their use as biomaterials, glycated collagens interact with cells in complex ways and a previous study has already shown the ability of a glycated collagen to redirect fibroblastoma cells from proliferation to differentiation. 26797224 4 25 theme backbone 661:668 arg1 weight 736:741 molecular weight 726:741 molecular weight 726:741 The number of variables involved (e.g., length and type of the collagen backbone, glycosaminoglycan species, sulfation type and pattern, molecular weight, number and length of side chains, etc.) makes possible to conceive an almost endless variety of artificial proteoglycans, each precisely tailored to a specific functional role. 26797224 4 25 theme backbone 661:668 arg1 type 708:711 sulfation type and pattern 698:723 type 708:711 The number of variables involved (e.g., length and type of the collagen backbone, glycosaminoglycan species, sulfation type and pattern, molecular weight, number and length of side chains, etc.) makes possible to conceive an almost endless variety of artificial proteoglycans, each precisely tailored to a specific functional role. 26797224 4 25 theme backbone 661:668 arg1 etc. 778:781 etc. 778:781 etc. 778:781 The number of variables involved (e.g., length and type of the collagen backbone, glycosaminoglycan species, sulfation type and pattern, molecular weight, number and length of side chains, etc.) makes possible to conceive an almost endless variety of artificial proteoglycans, each precisely tailored to a specific functional role. 26797224 4 25 theme backbone 661:668 arg1 length 629:634 length 629:634 length 629:634 The number of variables involved (e.g., length and type of the collagen backbone, glycosaminoglycan species, sulfation type and pattern, molecular weight, number and length of side chains, etc.) makes possible to conceive an almost endless variety of artificial proteoglycans, each precisely tailored to a specific functional role. 26797224 4 25 theme backbone 661:668 arg1 number 744:749 number 744:749 number 744:749 The number of variables involved (e.g., length and type of the collagen backbone, glycosaminoglycan species, sulfation type and pattern, molecular weight, number and length of side chains, etc.) makes possible to conceive an almost endless variety of artificial proteoglycans, each precisely tailored to a specific functional role. 26797224 4 25 theme backbone 661:668 arg1 pattern 717:723 sulfation type and pattern 698:723 pattern 717:723 The number of variables involved (e.g., length and type of the collagen backbone, glycosaminoglycan species, sulfation type and pattern, molecular weight, number and length of side chains, etc.) makes possible to conceive an almost endless variety of artificial proteoglycans, each precisely tailored to a specific functional role. 26797224 4 25 theme backbone 661:668 arg1 type 640:643 type 640:643 type 640:643 The number of variables involved (e.g., length and type of the collagen backbone, glycosaminoglycan species, sulfation type and pattern, molecular weight, number and length of side chains, etc.) makes possible to conceive an almost endless variety of artificial proteoglycans, each precisely tailored to a specific functional role. 26797224 4 25 theme backbone 661:668 arg1 length 755:760 length 755:760 length 755:760 The number of variables involved (e.g., length and type of the collagen backbone, glycosaminoglycan species, sulfation type and pattern, molecular weight, number and length of side chains, etc.) makes possible to conceive an almost endless variety of artificial proteoglycans, each precisely tailored to a specific functional role. 26797224 4 25 theme backbone 661:668 arg1 species 689:695 glycosaminoglycan species 671:695 glycosaminoglycan species 671:695 The number of variables involved (e.g., length and type of the collagen backbone, glycosaminoglycan species, sulfation type and pattern, molecular weight, number and length of side chains, etc.) makes possible to conceive an almost endless variety of artificial proteoglycans, each precisely tailored to a specific functional role. 26797224 2 26 theme lysine 418:423 arg1 backbone 475:482 a collagen molecule backbone 455:482 a collagen molecule backbone 455:482 At variance with natural proteoglycans, whose glycosaminoglycan chains are always O-linked via a tetrasaccharide bridge to the serine residues of a specific protein core, the present structure consists of chondroitin-6-sulfate chains directly bound to the lysine and hydroxylysine residues of a collagen molecule backbone. 26797224 2 26 theme lysine 418:423 arg1 residues 443:450 the lysine and hydroxylysine residues 414:450 residues 443:450 At variance with natural proteoglycans, whose glycosaminoglycan chains are always O-linked via a tetrasaccharide bridge to the serine residues of a specific protein core, the present structure consists of chondroitin-6-sulfate chains directly bound to the lysine and hydroxylysine residues of a collagen molecule backbone. 26797224 4 27 theme endless 821:827 arg1 each 866:869 each 866:869 each 866:869 The number of variables involved (e.g., length and type of the collagen backbone, glycosaminoglycan species, sulfation type and pattern, molecular weight, number and length of side chains, etc.) makes possible to conceive an almost endless variety of artificial proteoglycans, each precisely tailored to a specific functional role. 26797224 4 27 theme endless 821:827 arg1 variety 829:835 an almost endless variety 811:835 an almost endless variety of artificial proteoglycans, each precisely tailored to a specific functional role 811:918 The number of variables involved (e.g., length and type of the collagen backbone, glycosaminoglycan species, sulfation type and pattern, molecular weight, number and length of side chains, etc.) makes possible to conceive an almost endless variety of artificial proteoglycans, each precisely tailored to a specific functional role. 26797224 4 27 theme endless 821:827 arg1 proteoglycans 851:863 artificial proteoglycans 840:863 artificial proteoglycans 840:863 The number of variables involved (e.g., length and type of the collagen backbone, glycosaminoglycan species, sulfation type and pattern, molecular weight, number and length of side chains, etc.) makes possible to conceive an almost endless variety of artificial proteoglycans, each precisely tailored to a specific functional role. 26797224 4 28 theme molecular 726:734 arg1 length 629:634 length 629:634 length 629:634 The number of variables involved (e.g., length and type of the collagen backbone, glycosaminoglycan species, sulfation type and pattern, molecular weight, number and length of side chains, etc.) makes possible to conceive an almost endless variety of artificial proteoglycans, each precisely tailored to a specific functional role. 26797224 4 28 theme molecular 726:734 arg1 weight 736:741 molecular weight 726:741 molecular weight 726:741 The number of variables involved (e.g., length and type of the collagen backbone, glycosaminoglycan species, sulfation type and pattern, molecular weight, number and length of side chains, etc.) makes possible to conceive an almost endless variety of artificial proteoglycans, each precisely tailored to a specific functional role. 26797224 2 29 theme backbone 475:482 arg1 backbone 475:482 a collagen molecule backbone 455:482 a collagen molecule backbone 455:482 At variance with natural proteoglycans, whose glycosaminoglycan chains are always O-linked via a tetrasaccharide bridge to the serine residues of a specific protein core, the present structure consists of chondroitin-6-sulfate chains directly bound to the lysine and hydroxylysine residues of a collagen molecule backbone. 26797224 2 29 theme backbone 475:482 arg1 residues 443:450 the lysine and hydroxylysine residues 414:450 residues 443:450 At variance with natural proteoglycans, whose glycosaminoglycan chains are always O-linked via a tetrasaccharide bridge to the serine residues of a specific protein core, the present structure consists of chondroitin-6-sulfate chains directly bound to the lysine and hydroxylysine residues of a collagen molecule backbone. 26797224 5 30 theme previous 1024:1031 arg1 study 1033:1037 a previous study 1022:1037 a previous study 1022:1037 In addition to their use as biomaterials, glycated collagens interact with cells in complex ways and a previous study has already shown the ability of a glycated collagen to redirect fibroblastoma cells from proliferation to differentiation. 26797224 2 31 theme present 337:343 arg1 structure 345:353 the present structure 333:353 the present structure 333:353 At variance with natural proteoglycans, whose glycosaminoglycan chains are always O-linked via a tetrasaccharide bridge to the serine residues of a specific protein core, the present structure consists of chondroitin-6-sulfate chains directly bound to the lysine and hydroxylysine residues of a collagen molecule backbone. 26797224 4 32 theme functional 904:913 arg1 role 915:918 a specific functional role 893:918 a specific functional role 893:918 The number of variables involved (e.g., length and type of the collagen backbone, glycosaminoglycan species, sulfation type and pattern, molecular weight, number and length of side chains, etc.) makes possible to conceive an almost endless variety of artificial proteoglycans, each precisely tailored to a specific functional role. 26797224 2 33 theme glycosaminoglycan 208:224 arg1 chains 226:231 glycosaminoglycan chains 208:231 glycosaminoglycan chains 208:231 At variance with natural proteoglycans, whose glycosaminoglycan chains are always O-linked via a tetrasaccharide bridge to the serine residues of a specific protein core, the present structure consists of chondroitin-6-sulfate chains directly bound to the lysine and hydroxylysine residues of a collagen molecule backbone. 26797224 0 34 dep Synthesis 18:26 arg1 collaggrecan 4:15 The collaggrecan 0:15 The collaggrecan 0:15 The collaggrecan: Synthesis and visualization of an artificial proteoglycan. 26797224 4 35 theme sulfation 698:706 arg1 length 629:634 length 629:634 length 629:634 The number of variables involved (e.g., length and type of the collagen backbone, glycosaminoglycan species, sulfation type and pattern, molecular weight, number and length of side chains, etc.) makes possible to conceive an almost endless variety of artificial proteoglycans, each precisely tailored to a specific functional role. 26797224 4 35 theme sulfation 698:706 arg1 type 708:711 sulfation type and pattern 698:723 type 708:711 The number of variables involved (e.g., length and type of the collagen backbone, glycosaminoglycan species, sulfation type and pattern, molecular weight, number and length of side chains, etc.) makes possible to conceive an almost endless variety of artificial proteoglycans, each precisely tailored to a specific functional role. 26797224 4 36 theme specific 895:902 arg1 role 915:918 a specific functional role 893:918 a specific functional role 893:918 The number of variables involved (e.g., length and type of the collagen backbone, glycosaminoglycan species, sulfation type and pattern, molecular weight, number and length of side chains, etc.) makes possible to conceive an almost endless variety of artificial proteoglycans, each precisely tailored to a specific functional role. 26797224 4 37 dep length 629:634 arg1 e.g. 623:626 e.g. 623:626 e.g. 623:626 The number of variables involved (e.g., length and type of the collagen backbone, glycosaminoglycan species, sulfation type and pattern, molecular weight, number and length of side chains, etc.) makes possible to conceive an almost endless variety of artificial proteoglycans, each precisely tailored to a specific functional role. 26797224 5 38 theme glycated 963:970 arg1 collagens 972:980 glycated collagens 963:980 glycated collagens 963:980 In addition to their use as biomaterials, glycated collagens interact with cells in complex ways and a previous study has already shown the ability of a glycated collagen to redirect fibroblastoma cells from proliferation to differentiation. 26797224 3 39 theme atomic 555:560 arg1 microscopy 568:577 atomic force microscopy 555:577 atomic force microscopy 555:577 The resulting macromolecule has been characterized by histochemistry, atomic force microscopy and FTIR. 26797224 0 40 theme proteoglycan 63:74 arg1 visualization 32:44 visualization 32:44 visualization 32:44 The collaggrecan: Synthesis and visualization of an artificial proteoglycan. 26797224 0 40 theme proteoglycan 63:74 arg1 Synthesis 18:26 Synthesis 18:26 Synthesis 18:26 The collaggrecan: Synthesis and visualization of an artificial proteoglycan. 26797224 4 41 theme collagen 652:659 arg1 backbone 661:668 the collagen backbone 648:668 the collagen backbone 648:668 The number of variables involved (e.g., length and type of the collagen backbone, glycosaminoglycan species, sulfation type and pattern, molecular weight, number and length of side chains, etc.) makes possible to conceive an almost endless variety of artificial proteoglycans, each precisely tailored to a specific functional role. 26797224 2 42 theme tetrasaccharide 259:273 arg1 bridge 275:280 a tetrasaccharide bridge 257:280 a tetrasaccharide bridge to the serine residues of a specific protein core 257:330 At variance with natural proteoglycans, whose glycosaminoglycan chains are always O-linked via a tetrasaccharide bridge to the serine residues of a specific protein core, the present structure consists of chondroitin-6-sulfate chains directly bound to the lysine and hydroxylysine residues of a collagen molecule backbone. 26797224 5 43 dep use 942:944 arg1 addition 924:931 addition 924:931 addition 924:931 In addition to their use as biomaterials, glycated collagens interact with cells in complex ways and a previous study has already shown the ability of a glycated collagen to redirect fibroblastoma cells from proliferation to differentiation. 26797224 0 44 theme artificial 52:61 arg1 proteoglycan 63:74 an artificial proteoglycan 49:74 an artificial proteoglycan 49:74 The collaggrecan: Synthesis and visualization of an artificial proteoglycan. 26797224 2 45 theme chondroitin-6-sulfate 367:387 arg1 chains 389:394 chondroitin-6-sulfate chains 367:394 chondroitin-6-sulfate chains 367:394 At variance with natural proteoglycans, whose glycosaminoglycan chains are always O-linked via a tetrasaccharide bridge to the serine residues of a specific protein core, the present structure consists of chondroitin-6-sulfate chains directly bound to the lysine and hydroxylysine residues of a collagen molecule backbone. 28901741 5 0 theme partial 602:608 arg1 Glycoforest 583:593 Glycoforest 1.0 583:597 Glycoforest 1.0 583:597 To help alleviate this bottleneck, we present Glycoforest 1.0, a partial de novo algorithm for sequencing glycan structures based on MS/MS spectra. 28901741 5 0 theme partial 602:608 arg1 algorithm 618:626 a partial de novo algorithm 600:626 a partial de novo algorithm for sequencing glycan structures based on MS/MS spectra 600:682 To help alleviate this bottleneck, we present Glycoforest 1.0, a partial de novo algorithm for sequencing glycan structures based on MS/MS spectra. 28901741 9 1 theme glycan 1066:1071 arg1 structures 1073:1082 glycan structures 1066:1082 glycan structures 1066:1082 In addition, the Glycoforest algorithm detected glycan structures from MS/MS spectra missing a manual annotation. 28901741 1 2 theme raw 143:145 arg1 data 147:150 raw data 143:150 raw data 143:150 Tandem mass spectrometry, when combined with liquid chromatography and applied to complex mixtures, produces large amounts of raw data, which needs to be analyzed to identify molecular structures. 28901741 10 3 theme unannotated 1163:1173 arg1 spectra 1175:1181 1532 MS/MS previously unannotated spectra 1141:1181 1532 MS/MS previously unannotated spectra 1141:1181 In total 1532 MS/MS previously unannotated spectra were annotated by Glycoforest. 28901741 6 4 link O-linked 758:765 arg1 sets 720:723 two data sets 711:723 two data sets (human gastric and salmon mucosa O-linked glycomes) for which MS/MS spectra were annotated manually 711:823 Glycoforest was tested on two data sets (human gastric and salmon mucosa O-linked glycomes) for which MS/MS spectra were annotated manually. 28901741 6 4 link O-linked 758:765 arg1 glycomes 767:774 human gastric and salmon mucosa O-linked glycomes 726:774 human gastric and salmon mucosa O-linked glycomes 726:774 Glycoforest was tested on two data sets (human gastric and salmon mucosa O-linked glycomes) for which MS/MS spectra were annotated manually. 28901741 5 5 theme de 610:611 arg1 Glycoforest 583:593 Glycoforest 1.0 583:597 Glycoforest 1.0 583:597 To help alleviate this bottleneck, we present Glycoforest 1.0, a partial de novo algorithm for sequencing glycan structures based on MS/MS spectra. 28901741 5 5 theme de 610:611 arg1 algorithm 618:626 a partial de novo algorithm 600:626 a partial de novo algorithm for sequencing glycan structures based on MS/MS spectra 600:682 To help alleviate this bottleneck, we present Glycoforest 1.0, a partial de novo algorithm for sequencing glycan structures based on MS/MS spectra. 28901741 1 6 theme data 147:150 arg1 amounts 132:138 large amounts 126:138 large amounts 126:138 Tandem mass spectrometry, when combined with liquid chromatography and applied to complex mixtures, produces large amounts of raw data, which needs to be analyzed to identify molecular structures. 28901741 1 6 theme data 147:150 arg1 data 147:150 raw data 143:150 raw data 143:150 Tandem mass spectrometry, when combined with liquid chromatography and applied to complex mixtures, produces large amounts of raw data, which needs to be analyzed to identify molecular structures. 28901741 3 7 theme software 323:330 arg1 lack 281:284 a lack 279:284 a lack of high throughput glycan sequencing software 279:330 Due to a lack of high throughput glycan sequencing software, glycan spectra are predominantly sequenced manually. 28901741 7 8 theme test 889:892 arg1 cases 894:898 test cases 889:898 test cases 889:898 Glycoforest generated the human validated structure for 92% of test cases. 28901741 6 9 theme O-linked 758:765 arg1 sets 720:723 two data sets 711:723 two data sets (human gastric and salmon mucosa O-linked glycomes) for which MS/MS spectra were annotated manually 711:823 Glycoforest was tested on two data sets (human gastric and salmon mucosa O-linked glycomes) for which MS/MS spectra were annotated manually. 28901741 6 9 theme O-linked 758:765 arg1 glycomes 767:774 human gastric and salmon mucosa O-linked glycomes 726:774 human gastric and salmon mucosa O-linked glycomes 726:774 Glycoforest was tested on two data sets (human gastric and salmon mucosa O-linked glycomes) for which MS/MS spectra were annotated manually. 28901741 10 10 theme MS/MS 1146:1150 arg1 spectra 1175:1181 1532 MS/MS previously unannotated spectra 1141:1181 1532 MS/MS previously unannotated spectra 1141:1181 In total 1532 MS/MS previously unannotated spectra were annotated by Glycoforest. 28901741 8 11 dep % 965:965 arg1 match 953:957 match 953:957 match 953:957 The correct structure was found as the best scoring match for 70% and among the top 3 matches for 83% of test cases. 28901741 6 12 theme mucosa 751:756 arg1 sets 720:723 two data sets 711:723 two data sets (human gastric and salmon mucosa O-linked glycomes) for which MS/MS spectra were annotated manually 711:823 Glycoforest was tested on two data sets (human gastric and salmon mucosa O-linked glycomes) for which MS/MS spectra were annotated manually. 28901741 6 12 theme mucosa 751:756 arg1 glycomes 767:774 human gastric and salmon mucosa O-linked glycomes 726:774 human gastric and salmon mucosa O-linked glycomes 726:774 Glycoforest was tested on two data sets (human gastric and salmon mucosa O-linked glycomes) for which MS/MS spectra were annotated manually. 28901741 11 13 theme additional 1309:1318 arg1 spectra 1329:1335 an additional 50 MS/MS spectra 1306:1335 an additional 50 MS/MS spectra overlooked during manual annotation 1306:1371 A portion containing 521 spectra was manually checked confirming that Glycoforest annotated an additional 50 MS/MS spectra overlooked during manual annotation. 28901741 3 14 theme glycan 305:310 arg1 software 323:330 high throughput glycan sequencing software 289:330 high throughput glycan sequencing software 289:330 Due to a lack of high throughput glycan sequencing software, glycan spectra are predominantly sequenced manually. 28901741 6 15 theme salmon 744:749 arg1 sets 720:723 two data sets 711:723 two data sets (human gastric and salmon mucosa O-linked glycomes) for which MS/MS spectra were annotated manually 711:823 Glycoforest was tested on two data sets (human gastric and salmon mucosa O-linked glycomes) for which MS/MS spectra were annotated manually. 28901741 6 15 theme salmon 744:749 arg1 glycomes 767:774 human gastric and salmon mucosa O-linked glycomes 726:774 human gastric and salmon mucosa O-linked glycomes 726:774 Glycoforest was tested on two data sets (human gastric and salmon mucosa O-linked glycomes) for which MS/MS spectra were annotated manually. 28901741 1 16 theme liquid 62:67 arg1 chromatography 69:82 liquid chromatography 62:82 liquid chromatography 62:82 Tandem mass spectrometry, when combined with liquid chromatography and applied to complex mixtures, produces large amounts of raw data, which needs to be analyzed to identify molecular structures. 28901741 3 17 theme sequencing 312:321 arg1 software 323:330 high throughput glycan sequencing software 289:330 high throughput glycan sequencing software 289:330 Due to a lack of high throughput glycan sequencing software, glycan spectra are predominantly sequenced manually. 28901741 9 18 theme MS/MS 1089:1093 arg1 spectra 1095:1101 MS/MS spectra 1089:1101 MS/MS spectra missing a manual annotation 1089:1129 In addition, the Glycoforest algorithm detected glycan structures from MS/MS spectra missing a manual annotation. 28901741 4 19 used used 485:488 arg2 template 464:471 no direct template 454:471 no direct template that can be used to infer structures detectable in an organism 454:534 A challenge for writing glycan-sequencing software is that there is no direct template that can be used to infer structures detectable in an organism. 28901741 11 20 theme manual 1355:1360 arg1 annotation 1362:1371 manual annotation 1355:1371 manual annotation 1355:1371 A portion containing 521 spectra was manually checked confirming that Glycoforest annotated an additional 50 MS/MS spectra overlooked during manual annotation. 28901741 11 21 theme MS/MS 1323:1327 arg1 spectra 1329:1335 an additional 50 MS/MS spectra 1306:1335 an additional 50 MS/MS spectra overlooked during manual annotation 1306:1371 A portion containing 521 spectra was manually checked confirming that Glycoforest annotated an additional 50 MS/MS spectra overlooked during manual annotation. 28901741 7 22 theme cases 894:898 arg1 % 884:884 92% 882:884 92% of test cases 882:898 Glycoforest generated the human validated structure for 92% of test cases. 28901741 7 22 theme cases 894:898 arg1 cases 894:898 test cases 889:898 test cases 889:898 Glycoforest generated the human validated structure for 92% of test cases. 28901741 4 23 theme direct 457:462 arg1 template 464:471 no direct template 454:471 no direct template that can be used to infer structures detectable in an organism 454:534 A challenge for writing glycan-sequencing software is that there is no direct template that can be used to infer structures detectable in an organism. 28901741 6 24 theme gastric 732:738 arg1 sets 720:723 two data sets 711:723 two data sets (human gastric and salmon mucosa O-linked glycomes) for which MS/MS spectra were annotated manually 711:823 Glycoforest was tested on two data sets (human gastric and salmon mucosa O-linked glycomes) for which MS/MS spectra were annotated manually. 28901741 6 24 theme gastric 732:738 arg1 glycomes 767:774 human gastric and salmon mucosa O-linked glycomes 726:774 human gastric and salmon mucosa O-linked glycomes 726:774 Glycoforest was tested on two data sets (human gastric and salmon mucosa O-linked glycomes) for which MS/MS spectra were annotated manually. 28901741 2 25 used used 239:242 arg2 technique 219:227 This technique 214:227 This technique 214:227 This technique is widely used, particularly in glycomics. 28901741 11 26 contain containing 1224:1233 arg1 portion 1216:1222 A portion 1214:1222 A portion containing 521 spectra 1214:1245 A portion containing 521 spectra was manually checked confirming that Glycoforest annotated an additional 50 MS/MS spectra overlooked during manual annotation. 28901741 11 26 contain containing 1224:1233 arg2 spectra 1239:1245 521 spectra 1235:1245 521 spectra 1235:1245 A portion containing 521 spectra was manually checked confirming that Glycoforest annotated an additional 50 MS/MS spectra overlooked during manual annotation. 28901741 4 27 from organism 527:534 arg1 detectable 510:519 detectable 510:519 detectable 510:519 A challenge for writing glycan-sequencing software is that there is no direct template that can be used to infer structures detectable in an organism. 28901741 6 28 theme human 726:730 arg1 sets 720:723 two data sets 711:723 two data sets (human gastric and salmon mucosa O-linked glycomes) for which MS/MS spectra were annotated manually 711:823 Glycoforest was tested on two data sets (human gastric and salmon mucosa O-linked glycomes) for which MS/MS spectra were annotated manually. 28901741 6 28 theme human 726:730 arg1 glycomes 767:774 human gastric and salmon mucosa O-linked glycomes 726:774 human gastric and salmon mucosa O-linked glycomes 726:774 Glycoforest was tested on two data sets (human gastric and salmon mucosa O-linked glycomes) for which MS/MS spectra were annotated manually. 28901741 3 29 theme glycan 333:338 arg1 spectra 340:346 glycan spectra 333:346 glycan spectra 333:346 Due to a lack of high throughput glycan sequencing software, glycan spectra are predominantly sequenced manually. 28901741 9 30 theme manual 1113:1118 arg1 annotation 1120:1129 a manual annotation 1111:1129 a manual annotation 1111:1129 In addition, the Glycoforest algorithm detected glycan structures from MS/MS spectra missing a manual annotation. 28901741 8 31 theme scoring 945:951 arg1 matches 987:993 the best scoring match for 70% and among the top 3 matches 936:993 the best scoring match for 70% and among the top 3 matches for 83% of test cases 936:1015 The correct structure was found as the best scoring match for 70% and among the top 3 matches for 83% of test cases. 28901741 8 31 theme scoring 945:951 arg1 structure 913:921 The correct structure 901:921 The correct structure 901:921 The correct structure was found as the best scoring match for 70% and among the top 3 matches for 83% of test cases. 28901741 5 32 dep de 610:611 arg1 novo 613:616 novo 613:616 novo 613:616 To help alleviate this bottleneck, we present Glycoforest 1.0, a partial de novo algorithm for sequencing glycan structures based on MS/MS spectra. 28901741 1 33 theme complex 99:105 arg1 mixtures 107:114 complex mixtures 99:114 complex mixtures 99:114 Tandem mass spectrometry, when combined with liquid chromatography and applied to complex mixtures, produces large amounts of raw data, which needs to be analyzed to identify molecular structures. 28901741 4 34 from detectable 510:519 arg1 organism 527:534 an organism 524:534 an organism 524:534 A challenge for writing glycan-sequencing software is that there is no direct template that can be used to infer structures detectable in an organism. 28901741 5 35 theme MS/MS 670:674 arg1 spectra 676:682 MS/MS spectra 670:682 MS/MS spectra 670:682 To help alleviate this bottleneck, we present Glycoforest 1.0, a partial de novo algorithm for sequencing glycan structures based on MS/MS spectra. 28901741 11 36 theme 521 1235:1237 arg1 spectra 1239:1245 521 spectra 1235:1245 521 spectra 1235:1245 A portion containing 521 spectra was manually checked confirming that Glycoforest annotated an additional 50 MS/MS spectra overlooked during manual annotation. 28901741 8 37 theme test 1006:1009 arg1 cases 1011:1015 test cases 1006:1015 test cases 1006:1015 The correct structure was found as the best scoring match for 70% and among the top 3 matches for 83% of test cases. 28901741 6 38 theme data 715:718 arg1 glycomes 767:774 human gastric and salmon mucosa O-linked glycomes 726:774 human gastric and salmon mucosa O-linked glycomes 726:774 Glycoforest was tested on two data sets (human gastric and salmon mucosa O-linked glycomes) for which MS/MS spectra were annotated manually. 28901741 6 38 theme data 715:718 arg1 sets 720:723 two data sets 711:723 two data sets (human gastric and salmon mucosa O-linked glycomes) for which MS/MS spectra were annotated manually 711:823 Glycoforest was tested on two data sets (human gastric and salmon mucosa O-linked glycomes) for which MS/MS spectra were annotated manually. 28901741 4 39 theme detectable 510:519 arg1 structures 499:508 structures 499:508 structures detectable in an organism 499:534 A challenge for writing glycan-sequencing software is that there is no direct template that can be used to infer structures detectable in an organism. 28901741 5 40 theme sequencing 632:641 arg1 structures 650:659 sequencing glycan structures 632:659 sequencing glycan structures based on MS/MS spectra 632:682 To help alleviate this bottleneck, we present Glycoforest 1.0, a partial de novo algorithm for sequencing glycan structures based on MS/MS spectra. 28901741 6 41 theme MS/MS 787:791 arg1 spectra 793:799 MS/MS spectra 787:799 MS/MS spectra 787:799 Glycoforest was tested on two data sets (human gastric and salmon mucosa O-linked glycomes) for which MS/MS spectra were annotated manually. 28901741 1 42 theme Tandem 17:22 arg1 spectrometry 29:40 Tandem mass spectrometry 17:40 Tandem mass spectrometry 17:40 Tandem mass spectrometry, when combined with liquid chromatography and applied to complex mixtures, produces large amounts of raw data, which needs to be analyzed to identify molecular structures. 28901741 5 43 theme glycan 643:648 arg1 structures 650:659 sequencing glycan structures 632:659 sequencing glycan structures based on MS/MS spectra 632:682 To help alleviate this bottleneck, we present Glycoforest 1.0, a partial de novo algorithm for sequencing glycan structures based on MS/MS spectra. 28901741 1 44 theme mass 24:27 arg1 spectrometry 29:40 Tandem mass spectrometry 17:40 Tandem mass spectrometry 17:40 Tandem mass spectrometry, when combined with liquid chromatography and applied to complex mixtures, produces large amounts of raw data, which needs to be analyzed to identify molecular structures. 28901741 1 45 theme molecular 192:200 arg1 structures 202:211 molecular structures 192:211 molecular structures 192:211 Tandem mass spectrometry, when combined with liquid chromatography and applied to complex mixtures, produces large amounts of raw data, which needs to be analyzed to identify molecular structures. 28901741 8 46 theme cases 1011:1015 arg1 % 1001:1001 83% 999:1001 83% of test cases 999:1015 The correct structure was found as the best scoring match for 70% and among the top 3 matches for 83% of test cases. 28901741 8 46 theme cases 1011:1015 arg1 cases 1011:1015 test cases 1006:1015 test cases 1006:1015 The correct structure was found as the best scoring match for 70% and among the top 3 matches for 83% of test cases. 28901741 4 47 theme glycan-sequencing 410:426 arg1 software 428:435 glycan-sequencing software 410:435 glycan-sequencing software 410:435 A challenge for writing glycan-sequencing software is that there is no direct template that can be used to infer structures detectable in an organism. 28901741 9 48 theme Glycoforest 1035:1045 arg1 algorithm 1047:1055 the Glycoforest algorithm 1031:1055 the Glycoforest algorithm 1031:1055 In addition, the Glycoforest algorithm detected glycan structures from MS/MS spectra missing a manual annotation. 28901741 1 49 theme large 126:130 arg1 amounts 132:138 large amounts 126:138 large amounts 126:138 Tandem mass spectrometry, when combined with liquid chromatography and applied to complex mixtures, produces large amounts of raw data, which needs to be analyzed to identify molecular structures. 28901741 1 49 theme large 126:130 arg1 data 147:150 raw data 143:150 raw data 143:150 Tandem mass spectrometry, when combined with liquid chromatography and applied to complex mixtures, produces large amounts of raw data, which needs to be analyzed to identify molecular structures. 28901741 7 50 theme human 852:856 arg1 structure 868:876 the human validated structure 848:876 the human validated structure for 92% of test cases 848:898 Glycoforest generated the human validated structure for 92% of test cases. 28901741 3 51 theme high 289:292 arg1 software 323:330 high throughput glycan sequencing software 289:330 high throughput glycan sequencing software 289:330 Due to a lack of high throughput glycan sequencing software, glycan spectra are predominantly sequenced manually. 28901741 7 52 theme validated 858:866 arg1 structure 868:876 the human validated structure 848:876 the human validated structure for 92% of test cases 848:898 Glycoforest generated the human validated structure for 92% of test cases. 28901741 3 53 theme throughput 294:303 arg1 software 323:330 high throughput glycan sequencing software 289:330 high throughput glycan sequencing software 289:330 Due to a lack of high throughput glycan sequencing software, glycan spectra are predominantly sequenced manually. 28901741 8 54 theme correct 905:911 arg1 structure 913:921 The correct structure 901:921 The correct structure 901:921 The correct structure was found as the best scoring match for 70% and among the top 3 matches for 83% of test cases. 28901741 8 54 theme correct 905:911 arg1 matches 987:993 the best scoring match for 70% and among the top 3 matches 936:993 the best scoring match for 70% and among the top 3 matches for 83% of test cases 936:1015 The correct structure was found as the best scoring match for 70% and among the top 3 matches for 83% of test cases. 28814130 0 0 theme mucin 101:105 arg1 utilization 114:124 mucin glycan utilization 101:124 mucin glycan utilization 101:124 Identification and characterization of a sulfoglycosidase from Bifidobacterium bifidum implicated in mucin glycan utilization. 28814130 0 1 from characterization 19:34 arg1 bifidum 79:85 Bifidobacterium bifidum 63:85 Bifidobacterium bifidum 63:85 Identification and characterization of a sulfoglycosidase from Bifidobacterium bifidum implicated in mucin glycan utilization. 28814130 3 2 theme several 547:553 arg1 strains 571:577 several Bifidobacterium strains 547:577 several Bifidobacterium strains 547:577 Here, we examined the abilities of several Bifidobacterium strains to degrade a sulfated glycan substrate and identified a 6-sulfo-β-d-N-acetylglucosaminidase, also termed sulfoglycosidase, encoded by bbhII from Bifidobacterium bifidum JCM 7004. 28814130 1 3 theme carbon 288:293 arg1 carbohydrates 271:283 those carbohydrates 265:283 those carbohydrates 265:283 Human gut symbiont bifidobacteria possess carbohydrate-degrading enzymes that act on the O-linked glycans of intestinal mucins to utilize those carbohydrates as carbon sources. 28814130 1 3 theme carbon 288:293 arg1 sources 295:301 carbon sources 288:301 carbon sources 288:301 Human gut symbiont bifidobacteria possess carbohydrate-degrading enzymes that act on the O-linked glycans of intestinal mucins to utilize those carbohydrates as carbon sources. 28814130 3 4 theme Bifidobacterium 555:569 arg1 strains 571:577 several Bifidobacterium strains 547:577 several Bifidobacterium strains 547:577 Here, we examined the abilities of several Bifidobacterium strains to degrade a sulfated glycan substrate and identified a 6-sulfo-β-d-N-acetylglucosaminidase, also termed sulfoglycosidase, encoded by bbhII from Bifidobacterium bifidum JCM 7004. 28814130 6 5 theme sulfated 1153:1160 arg1 glycans 1162:1168 sulfated glycans 1153:1168 sulfated glycans of mucin 1153:1177 This de-capping activity may promote utilization of sulfated glycans of mucin by other bacteria including bifidobacteria, thereby establishing the symbiotic relationship between human and gut microbes. 28814130 0 6 from Identification 0:13 arg1 bifidum 79:85 Bifidobacterium bifidum 63:85 Bifidobacterium bifidum 63:85 Identification and characterization of a sulfoglycosidase from Bifidobacterium bifidum implicated in mucin glycan utilization. 28814130 3 7 theme strains 571:577 arg1 abilities 534:542 the abilities 530:542 the abilities of several Bifidobacterium strains 530:577 Here, we examined the abilities of several Bifidobacterium strains to degrade a sulfated glycan substrate and identified a 6-sulfo-β-d-N-acetylglucosaminidase, also termed sulfoglycosidase, encoded by bbhII from Bifidobacterium bifidum JCM 7004. 28814130 3 8 theme sulfated 592:599 arg1 substrate 608:616 a sulfated glycan substrate 590:616 a sulfated glycan substrate 590:616 Here, we examined the abilities of several Bifidobacterium strains to degrade a sulfated glycan substrate and identified a 6-sulfo-β-d-N-acetylglucosaminidase, also termed sulfoglycosidase, encoded by bbhII from Bifidobacterium bifidum JCM 7004. 28814130 2 9 theme mucin 333:337 arg1 degradation 353:363 mucin type O-glycan degradation 333:363 mucin type O-glycan degradation by bifidobacteria 333:381 However, our knowledge about mucin type O-glycan degradation by bifidobacteria remains fragmentary, especially regarding how they decompose sulfated glycans, which are abundantly found in mucin sugar-chains. 28814130 0 10 theme glycan 107:112 arg1 utilization 114:124 mucin glycan utilization 101:124 mucin glycan utilization 101:124 Identification and characterization of a sulfoglycosidase from Bifidobacterium bifidum implicated in mucin glycan utilization. 28814130 3 11 theme glycan 601:606 arg1 substrate 608:616 a sulfated glycan substrate 590:616 a sulfated glycan substrate 590:616 Here, we examined the abilities of several Bifidobacterium strains to degrade a sulfated glycan substrate and identified a 6-sulfo-β-d-N-acetylglucosaminidase, also termed sulfoglycosidase, encoded by bbhII from Bifidobacterium bifidum JCM 7004. 28814130 4 12 theme substrate 795:803 arg1 preference 805:814 a substrate preference 793:814 a substrate preference toward 6-sulfated and 3,4-disulfated N-acetylglucosamines over non-sulfated and 3-sulfated N-acetylglucosamines 793:926 A recombinant BbhII protein showed a substrate preference toward 6-sulfated and 3,4-disulfated N-acetylglucosamines over non-sulfated and 3-sulfated N-acetylglucosamines. 28814130 1 13 link O-linked 216:223 arg1 glycans 225:231 the O-linked glycans 212:231 the O-linked glycans of intestinal mucins 212:252 Human gut symbiont bifidobacteria possess carbohydrate-degrading enzymes that act on the O-linked glycans of intestinal mucins to utilize those carbohydrates as carbon sources. 28814130 6 14 theme symbiotic 1248:1256 arg1 relationship 1258:1269 the symbiotic relationship 1244:1269 the symbiotic relationship between human and gut microbes 1244:1300 This de-capping activity may promote utilization of sulfated glycans of mucin by other bacteria including bifidobacteria, thereby establishing the symbiotic relationship between human and gut microbes. 28814130 4 15 theme 3-sulfated 896:905 arg1 N-acetylglucosamines 907:926 non-sulfated and 3-sulfated N-acetylglucosamines 879:926 non-sulfated and 3-sulfated N-acetylglucosamines 879:926 A recombinant BbhII protein showed a substrate preference toward 6-sulfated and 3,4-disulfated N-acetylglucosamines over non-sulfated and 3-sulfated N-acetylglucosamines. 28814130 3 16 dep 6-sulfo-β-d-N-acetylglucosaminidase 635:669 arg1 termed 677:682 termed 677:682 termed 677:682 Here, we examined the abilities of several Bifidobacterium strains to degrade a sulfated glycan substrate and identified a 6-sulfo-β-d-N-acetylglucosaminidase, also termed sulfoglycosidase, encoded by bbhII from Bifidobacterium bifidum JCM 7004. 28814130 6 17 theme glycans 1162:1168 arg1 utilization 1138:1148 utilization 1138:1148 utilization of sulfated glycans of mucin 1138:1177 This de-capping activity may promote utilization of sulfated glycans of mucin by other bacteria including bifidobacteria, thereby establishing the symbiotic relationship between human and gut microbes. 28814130 2 18 theme sulfated 444:451 arg1 glycans 453:459 sulfated glycans 444:459 sulfated glycans 444:459 However, our knowledge about mucin type O-glycan degradation by bifidobacteria remains fragmentary, especially regarding how they decompose sulfated glycans, which are abundantly found in mucin sugar-chains. 28814130 1 19 theme O-linked 216:223 arg1 glycans 225:231 the O-linked glycans 212:231 the O-linked glycans of intestinal mucins 212:252 Human gut symbiont bifidobacteria possess carbohydrate-degrading enzymes that act on the O-linked glycans of intestinal mucins to utilize those carbohydrates as carbon sources. 28814130 2 20 theme mucin 492:496 arg1 sugar-chains 498:509 mucin sugar-chains 492:509 mucin sugar-chains 492:509 However, our knowledge about mucin type O-glycan degradation by bifidobacteria remains fragmentary, especially regarding how they decompose sulfated glycans, which are abundantly found in mucin sugar-chains. 28814130 2 21 located found 483:487 arg1 sugar-chains 498:509 mucin sugar-chains 492:509 mucin sugar-chains 492:509 However, our knowledge about mucin type O-glycan degradation by bifidobacteria remains fragmentary, especially regarding how they decompose sulfated glycans, which are abundantly found in mucin sugar-chains. 28814130 2 21 located found 483:487 arg2 glycans 453:459 sulfated glycans 444:459 sulfated glycans 444:459 However, our knowledge about mucin type O-glycan degradation by bifidobacteria remains fragmentary, especially regarding how they decompose sulfated glycans, which are abundantly found in mucin sugar-chains. 28814130 2 22 theme O-glycan 344:351 arg1 degradation 353:363 mucin type O-glycan degradation 333:363 mucin type O-glycan degradation by bifidobacteria 333:381 However, our knowledge about mucin type O-glycan degradation by bifidobacteria remains fragmentary, especially regarding how they decompose sulfated glycans, which are abundantly found in mucin sugar-chains. 28814130 5 23 theme porcine 1002:1008 arg1 mucin 1018:1022 porcine gastric mucin 1002:1022 porcine gastric mucin 1002:1022 The purified BbhII directly released 6-sulfated N-acetylglucosamine from porcine gastric mucin and the expression of bbhII was moderately induced in the presence of mucin. 28814130 2 24 theme type 339:342 arg1 degradation 353:363 mucin type O-glycan degradation 333:363 mucin type O-glycan degradation by bifidobacteria 333:381 However, our knowledge about mucin type O-glycan degradation by bifidobacteria remains fragmentary, especially regarding how they decompose sulfated glycans, which are abundantly found in mucin sugar-chains. 28814130 4 25 theme 6-sulfated 823:832 arg1 N-acetylglucosamines 853:872 6-sulfated and 3,4-disulfated N-acetylglucosamines 823:872 6-sulfated and 3,4-disulfated N-acetylglucosamines 823:872 A recombinant BbhII protein showed a substrate preference toward 6-sulfated and 3,4-disulfated N-acetylglucosamines over non-sulfated and 3-sulfated N-acetylglucosamines. 28814130 5 26 theme mucin 1094:1098 arg1 presence 1082:1089 the presence 1078:1089 the presence of mucin 1078:1098 The purified BbhII directly released 6-sulfated N-acetylglucosamine from porcine gastric mucin and the expression of bbhII was moderately induced in the presence of mucin. 28814130 3 27 theme Bifidobacterium 724:738 arg1 7004 752:755 Bifidobacterium bifidum JCM 7004 724:755 Bifidobacterium bifidum JCM 7004 724:755 Here, we examined the abilities of several Bifidobacterium strains to degrade a sulfated glycan substrate and identified a 6-sulfo-β-d-N-acetylglucosaminidase, also termed sulfoglycosidase, encoded by bbhII from Bifidobacterium bifidum JCM 7004. 28814130 1 28 theme Human 127:131 arg1 bifidobacteria 146:159 Human gut symbiont bifidobacteria 127:159 Human gut symbiont bifidobacteria 127:159 Human gut symbiont bifidobacteria possess carbohydrate-degrading enzymes that act on the O-linked glycans of intestinal mucins to utilize those carbohydrates as carbon sources. 28814130 1 29 theme intestinal 236:245 arg1 mucins 247:252 intestinal mucins 236:252 intestinal mucins 236:252 Human gut symbiont bifidobacteria possess carbohydrate-degrading enzymes that act on the O-linked glycans of intestinal mucins to utilize those carbohydrates as carbon sources. 28814130 0 30 theme sulfoglycosidase 41:56 arg1 characterization 19:34 characterization 19:34 characterization 19:34 Identification and characterization of a sulfoglycosidase from Bifidobacterium bifidum implicated in mucin glycan utilization. 28814130 0 30 theme sulfoglycosidase 41:56 arg1 Identification 0:13 Identification 0:13 Identification 0:13 Identification and characterization of a sulfoglycosidase from Bifidobacterium bifidum implicated in mucin glycan utilization. 28814130 6 31 theme de-capping 1106:1115 arg1 activity 1117:1124 This de-capping activity 1101:1124 This de-capping activity 1101:1124 This de-capping activity may promote utilization of sulfated glycans of mucin by other bacteria including bifidobacteria, thereby establishing the symbiotic relationship between human and gut microbes. 28814130 3 32 theme bifidum 740:746 arg1 7004 752:755 Bifidobacterium bifidum JCM 7004 724:755 Bifidobacterium bifidum JCM 7004 724:755 Here, we examined the abilities of several Bifidobacterium strains to degrade a sulfated glycan substrate and identified a 6-sulfo-β-d-N-acetylglucosaminidase, also termed sulfoglycosidase, encoded by bbhII from Bifidobacterium bifidum JCM 7004. 28814130 1 33 theme mucins 247:252 arg1 glycans 225:231 the O-linked glycans 212:231 the O-linked glycans of intestinal mucins 212:252 Human gut symbiont bifidobacteria possess carbohydrate-degrading enzymes that act on the O-linked glycans of intestinal mucins to utilize those carbohydrates as carbon sources. 28814130 4 34 theme BbhII 772:776 arg1 protein 778:784 A recombinant BbhII protein 758:784 A recombinant BbhII protein 758:784 A recombinant BbhII protein showed a substrate preference toward 6-sulfated and 3,4-disulfated N-acetylglucosamines over non-sulfated and 3-sulfated N-acetylglucosamines. 28814130 5 35 theme gastric 1010:1016 arg1 mucin 1018:1022 porcine gastric mucin 1002:1022 porcine gastric mucin 1002:1022 The purified BbhII directly released 6-sulfated N-acetylglucosamine from porcine gastric mucin and the expression of bbhII was moderately induced in the presence of mucin. 28814130 0 36 from bifidum 79:85 arg1 characterization 19:34 characterization 19:34 characterization 19:34 Identification and characterization of a sulfoglycosidase from Bifidobacterium bifidum implicated in mucin glycan utilization. 28814130 0 36 from bifidum 79:85 arg1 sulfoglycosidase 41:56 a sulfoglycosidase 39:56 a sulfoglycosidase from Bifidobacterium bifidum 39:85 Identification and characterization of a sulfoglycosidase from Bifidobacterium bifidum implicated in mucin glycan utilization. 28814130 0 36 from bifidum 79:85 arg1 Identification 0:13 Identification 0:13 Identification 0:13 Identification and characterization of a sulfoglycosidase from Bifidobacterium bifidum implicated in mucin glycan utilization. 28814130 3 37 theme 6-sulfo-β-d-N-acetylglucosaminidase 635:669 arg1 sulfoglycosidase 684:699 a 6-sulfo-β-d-N-acetylglucosaminidase, also termed sulfoglycosidase 633:699 a 6-sulfo-β-d-N-acetylglucosaminidase, also termed sulfoglycosidase 633:699 Here, we examined the abilities of several Bifidobacterium strains to degrade a sulfated glycan substrate and identified a 6-sulfo-β-d-N-acetylglucosaminidase, also termed sulfoglycosidase, encoded by bbhII from Bifidobacterium bifidum JCM 7004. 28814130 1 38 theme gut 133:135 arg1 bifidobacteria 146:159 Human gut symbiont bifidobacteria 127:159 Human gut symbiont bifidobacteria 127:159 Human gut symbiont bifidobacteria possess carbohydrate-degrading enzymes that act on the O-linked glycans of intestinal mucins to utilize those carbohydrates as carbon sources. 28814130 5 39 theme purified 933:940 arg1 BbhII 942:946 The purified BbhII 929:946 The purified BbhII 929:946 The purified BbhII directly released 6-sulfated N-acetylglucosamine from porcine gastric mucin and the expression of bbhII was moderately induced in the presence of mucin. 28814130 6 40 dep human 1279:1283 arg1 microbes 1293:1300 microbes 1293:1300 microbes 1293:1300 This de-capping activity may promote utilization of sulfated glycans of mucin by other bacteria including bifidobacteria, thereby establishing the symbiotic relationship between human and gut microbes. 28814130 1 41 theme symbiont 137:144 arg1 bifidobacteria 146:159 Human gut symbiont bifidobacteria 127:159 Human gut symbiont bifidobacteria 127:159 Human gut symbiont bifidobacteria possess carbohydrate-degrading enzymes that act on the O-linked glycans of intestinal mucins to utilize those carbohydrates as carbon sources. 28814130 6 42 theme other 1182:1186 arg1 bifidobacteria 1207:1220 bifidobacteria 1207:1220 bifidobacteria 1207:1220 This de-capping activity may promote utilization of sulfated glycans of mucin by other bacteria including bifidobacteria, thereby establishing the symbiotic relationship between human and gut microbes. 28814130 6 42 theme other 1182:1186 arg1 bacteria 1188:1195 other bacteria 1182:1195 other bacteria including bifidobacteria 1182:1220 This de-capping activity may promote utilization of sulfated glycans of mucin by other bacteria including bifidobacteria, thereby establishing the symbiotic relationship between human and gut microbes. 28814130 3 43 theme JCM 748:750 arg1 7004 752:755 Bifidobacterium bifidum JCM 7004 724:755 Bifidobacterium bifidum JCM 7004 724:755 Here, we examined the abilities of several Bifidobacterium strains to degrade a sulfated glycan substrate and identified a 6-sulfo-β-d-N-acetylglucosaminidase, also termed sulfoglycosidase, encoded by bbhII from Bifidobacterium bifidum JCM 7004. 28814130 4 44 theme non-sulfated 879:890 arg1 N-acetylglucosamines 907:926 non-sulfated and 3-sulfated N-acetylglucosamines 879:926 non-sulfated and 3-sulfated N-acetylglucosamines 879:926 A recombinant BbhII protein showed a substrate preference toward 6-sulfated and 3,4-disulfated N-acetylglucosamines over non-sulfated and 3-sulfated N-acetylglucosamines. 28814130 4 45 theme 3,4-disulfated 838:851 arg1 N-acetylglucosamines 853:872 6-sulfated and 3,4-disulfated N-acetylglucosamines 823:872 6-sulfated and 3,4-disulfated N-acetylglucosamines 823:872 A recombinant BbhII protein showed a substrate preference toward 6-sulfated and 3,4-disulfated N-acetylglucosamines over non-sulfated and 3-sulfated N-acetylglucosamines. 28814130 5 46 theme bbhII 1046:1050 arg1 expression 1032:1041 the expression 1028:1041 the expression of bbhII 1028:1050 The purified BbhII directly released 6-sulfated N-acetylglucosamine from porcine gastric mucin and the expression of bbhII was moderately induced in the presence of mucin. 28814130 1 47 theme carbohydrate-degrading 169:190 arg1 enzymes 192:198 carbohydrate-degrading enzymes 169:198 carbohydrate-degrading enzymes that act on the O-linked glycans of intestinal mucins to utilize those carbohydrates as carbon sources 169:301 Human gut symbiont bifidobacteria possess carbohydrate-degrading enzymes that act on the O-linked glycans of intestinal mucins to utilize those carbohydrates as carbon sources. 28814130 6 48 theme mucin 1173:1177 arg1 glycans 1162:1168 sulfated glycans 1153:1168 sulfated glycans of mucin 1153:1177 This de-capping activity may promote utilization of sulfated glycans of mucin by other bacteria including bifidobacteria, thereby establishing the symbiotic relationship between human and gut microbes. 28814130 3 49 from 7004 752:755 arg1 bbhII 713:717 bbhII 713:717 bbhII from Bifidobacterium bifidum JCM 7004 713:755 Here, we examined the abilities of several Bifidobacterium strains to degrade a sulfated glycan substrate and identified a 6-sulfo-β-d-N-acetylglucosaminidase, also termed sulfoglycosidase, encoded by bbhII from Bifidobacterium bifidum JCM 7004. 28814130 1 50 contain possess 161:167 arg1 bifidobacteria 146:159 Human gut symbiont bifidobacteria 127:159 Human gut symbiont bifidobacteria 127:159 Human gut symbiont bifidobacteria possess carbohydrate-degrading enzymes that act on the O-linked glycans of intestinal mucins to utilize those carbohydrates as carbon sources. 28814130 1 50 contain possess 161:167 arg2 enzymes 192:198 carbohydrate-degrading enzymes 169:198 carbohydrate-degrading enzymes that act on the O-linked glycans of intestinal mucins to utilize those carbohydrates as carbon sources 169:301 Human gut symbiont bifidobacteria possess carbohydrate-degrading enzymes that act on the O-linked glycans of intestinal mucins to utilize those carbohydrates as carbon sources. 28814130 5 51 theme 6-sulfated 966:975 arg1 N-acetylglucosamine 977:995 6-sulfated N-acetylglucosamine 966:995 6-sulfated N-acetylglucosamine from porcine gastric mucin 966:1022 The purified BbhII directly released 6-sulfated N-acetylglucosamine from porcine gastric mucin and the expression of bbhII was moderately induced in the presence of mucin. 28814130 5 52 from mucin 1018:1022 arg1 N-acetylglucosamine 977:995 6-sulfated N-acetylglucosamine 966:995 6-sulfated N-acetylglucosamine from porcine gastric mucin 966:1022 The purified BbhII directly released 6-sulfated N-acetylglucosamine from porcine gastric mucin and the expression of bbhII was moderately induced in the presence of mucin. 28814130 4 53 theme recombinant 760:770 arg1 protein 778:784 A recombinant BbhII protein 758:784 A recombinant BbhII protein 758:784 A recombinant BbhII protein showed a substrate preference toward 6-sulfated and 3,4-disulfated N-acetylglucosamines over non-sulfated and 3-sulfated N-acetylglucosamines. 27556227 6 0 theme T. 1161:1162 arg1 glycoconjugates 1178:1192 T. cruzi surface glycoconjugates 1161:1192 T. cruzi surface glycoconjugates 1161:1192 These results confirm the classification of the Silvio X10/1 strain in group T. cruzi I. Again, it is noted that the study of T. cruzi surface glycoconjugates confirm the molecular results and the hypothesis that surface glycoconjugates may be interesting biomarker for the differentiation of trypanosomatid strains. 27556227 2 1 theme drug 343:346 arg1 susceptibility 348:361 drug susceptibility 343:361 drug susceptibility 343:361 One of the main obstacles to the treatment of Chagas disease is the genetic and phenotypical variance displayed by T. cruzi strains, resulting in differences in morphology, virulence, pathogenicity and drug susceptibility. 27556227 4 2 from position 670:677 arg1 Tc-mucins 725:733 Tc-mucins 725:733 Tc-mucins 725:733 We demonstrated the presence of a β-galactofuranose (β-Galf) unity linked to the O-4 position of the α-N-acetylglucosamine (α-GlcNAc)O-4 in Tc-mucins. 27556227 6 3 theme trypanosomatid 1328:1341 arg1 strains 1343:1349 trypanosomatid strains 1328:1349 trypanosomatid strains 1328:1349 These results confirm the classification of the Silvio X10/1 strain in group T. cruzi I. Again, it is noted that the study of T. cruzi surface glycoconjugates confirm the molecular results and the hypothesis that surface glycoconjugates may be interesting biomarker for the differentiation of trypanosomatid strains. 27556227 2 4 theme Chagas 187:192 arg1 disease 194:200 Chagas disease 187:200 Chagas disease 187:200 One of the main obstacles to the treatment of Chagas disease is the genetic and phenotypical variance displayed by T. cruzi strains, resulting in differences in morphology, virulence, pathogenicity and drug susceptibility. 27556227 5 5 theme GlcN-Ins-PO4 877:888 arg1 core 890:893 the Man4(AEP)GlcN-Ins-PO4 core 864:893 the Man4(AEP)GlcN-Ins-PO4 core 864:893 GIPLs analysis showed that the lipidic portion is exclusively composed of ceramide and the PI-oligossacharidic portion contains the Man4(AEP)GlcN-Ins-PO4 core, substituted by ethanolamine-phosphate (EtNP) on the third distal mannose from inositol, which may or may not have a terminal β Galf unity. 27556227 3 6 from mucins 505:510 arg1 chains 493:498 the O-linked chains 480:498 the O-linked chains from mucins and glycoinositolphospholipids (GIPLs) of the Silvio X10 clone 1 strain 480:582 To better understand the role of glycoconjungates in Chagas disease, we performed the molecular characterization of the O-linked chains from mucins and glycoinositolphospholipids (GIPLs) of the Silvio X10 clone 1 strain. 27556227 3 6 from mucins 505:510 arg1 characterization 460:475 the molecular characterization 446:475 the molecular characterization of the O-linked chains from mucins and glycoinositolphospholipids (GIPLs) of the Silvio X10 clone 1 strain 446:582 To better understand the role of glycoconjungates in Chagas disease, we performed the molecular characterization of the O-linked chains from mucins and glycoinositolphospholipids (GIPLs) of the Silvio X10 clone 1 strain. 27556227 6 7 theme X10/1 1090:1094 arg1 strain 1096:1101 the Silvio X10/1 strain 1079:1101 the Silvio X10/1 strain 1079:1101 These results confirm the classification of the Silvio X10/1 strain in group T. cruzi I. Again, it is noted that the study of T. cruzi surface glycoconjugates confirm the molecular results and the hypothesis that surface glycoconjugates may be interesting biomarker for the differentiation of trypanosomatid strains. 27556227 0 8 theme TcI 92:94 arg1 genotype 96:103 TcI genotype 92:103 TcI genotype 92:103 Expanding the knowledge of the chemical structure of glycoconjugates from Trypanosoma cruzi TcI genotype. 27556227 2 9 theme main 152:155 arg1 obstacles 157:165 the main obstacles 148:165 the main obstacles to the treatment of Chagas disease 148:200 One of the main obstacles to the treatment of Chagas disease is the genetic and phenotypical variance displayed by T. cruzi strains, resulting in differences in morphology, virulence, pathogenicity and drug susceptibility. 27556227 5 10 contain contains 855:862 arg2 core 890:893 the Man4(AEP)GlcN-Ins-PO4 core 864:893 the Man4(AEP)GlcN-Ins-PO4 core 864:893 GIPLs analysis showed that the lipidic portion is exclusively composed of ceramide and the PI-oligossacharidic portion contains the Man4(AEP)GlcN-Ins-PO4 core, substituted by ethanolamine-phosphate (EtNP) on the third distal mannose from inositol, which may or may not have a terminal β Galf unity. 27556227 5 10 contain contains 855:862 arg1 portion 847:853 the PI-oligossacharidic portion 823:853 the PI-oligossacharidic portion 823:853 GIPLs analysis showed that the lipidic portion is exclusively composed of ceramide and the PI-oligossacharidic portion contains the Man4(AEP)GlcN-Ins-PO4 core, substituted by ethanolamine-phosphate (EtNP) on the third distal mannose from inositol, which may or may not have a terminal β Galf unity. 27556227 5 11 from inositol 974:981 arg1 mannose 961:967 the third distal mannose 944:967 the third distal mannose from inositol 944:981 GIPLs analysis showed that the lipidic portion is exclusively composed of ceramide and the PI-oligossacharidic portion contains the Man4(AEP)GlcN-Ins-PO4 core, substituted by ethanolamine-phosphate (EtNP) on the third distal mannose from inositol, which may or may not have a terminal β Galf unity. 27556227 0 12 from structure 40:48 arg1 Trypanosoma 74:84 Trypanosoma 74:84 Trypanosoma 74:84 Expanding the knowledge of the chemical structure of glycoconjugates from Trypanosoma cruzi TcI genotype. 27556227 0 12 from structure 40:48 arg1 genotype 96:103 TcI genotype 92:103 TcI genotype 92:103 Expanding the knowledge of the chemical structure of glycoconjugates from Trypanosoma cruzi TcI genotype. 27556227 6 13 theme glycoconjugates 1178:1192 arg1 study 1152:1156 the study 1148:1156 the study of T. cruzi surface glycoconjugates 1148:1192 These results confirm the classification of the Silvio X10/1 strain in group T. cruzi I. Again, it is noted that the study of T. cruzi surface glycoconjugates confirm the molecular results and the hypothesis that surface glycoconjugates may be interesting biomarker for the differentiation of trypanosomatid strains. 27556227 3 14 from glycoinositolphospholipids 516:541 arg1 chains 493:498 the O-linked chains 480:498 the O-linked chains from mucins and glycoinositolphospholipids (GIPLs) of the Silvio X10 clone 1 strain 480:582 To better understand the role of glycoconjungates in Chagas disease, we performed the molecular characterization of the O-linked chains from mucins and glycoinositolphospholipids (GIPLs) of the Silvio X10 clone 1 strain. 27556227 3 14 from glycoinositolphospholipids 516:541 arg1 characterization 460:475 the molecular characterization 446:475 the molecular characterization of the O-linked chains from mucins and glycoinositolphospholipids (GIPLs) of the Silvio X10 clone 1 strain 446:582 To better understand the role of glycoconjungates in Chagas disease, we performed the molecular characterization of the O-linked chains from mucins and glycoinositolphospholipids (GIPLs) of the Silvio X10 clone 1 strain. 27556227 5 15 theme third 948:952 arg1 mannose 961:967 the third distal mannose 944:967 the third distal mannose from inositol 944:981 GIPLs analysis showed that the lipidic portion is exclusively composed of ceramide and the PI-oligossacharidic portion contains the Man4(AEP)GlcN-Ins-PO4 core, substituted by ethanolamine-phosphate (EtNP) on the third distal mannose from inositol, which may or may not have a terminal β Galf unity. 27556227 3 16 theme Chagas 417:422 arg1 disease 424:430 Chagas disease 417:430 Chagas disease 417:430 To better understand the role of glycoconjungates in Chagas disease, we performed the molecular characterization of the O-linked chains from mucins and glycoinositolphospholipids (GIPLs) of the Silvio X10 clone 1 strain. 27556227 4 17 theme unity 646:650 arg1 presence 605:612 the presence 601:612 the presence of a β-galactofuranose (β-Galf) unity linked to the O-4 position of the α-N-acetylglucosamine (α-GlcNAc)O-4 in Tc-mucins 601:733 We demonstrated the presence of a β-galactofuranose (β-Galf) unity linked to the O-4 position of the α-N-acetylglucosamine (α-GlcNAc)O-4 in Tc-mucins. 27556227 6 18 theme interesting 1279:1289 arg1 hypothesis 1232:1241 the hypothesis 1228:1241 the hypothesis that surface glycoconjugates 1228:1270 These results confirm the classification of the Silvio X10/1 strain in group T. cruzi I. Again, it is noted that the study of T. cruzi surface glycoconjugates confirm the molecular results and the hypothesis that surface glycoconjugates may be interesting biomarker for the differentiation of trypanosomatid strains. 27556227 6 18 theme interesting 1279:1289 arg1 biomarker 1291:1299 interesting biomarker 1279:1299 interesting biomarker for the differentiation of trypanosomatid strains 1279:1349 These results confirm the classification of the Silvio X10/1 strain in group T. cruzi I. Again, it is noted that the study of T. cruzi surface glycoconjugates confirm the molecular results and the hypothesis that surface glycoconjugates may be interesting biomarker for the differentiation of trypanosomatid strains. 27556227 3 19 theme glycoconjungates 397:412 arg1 role 389:392 the role 385:392 the role of glycoconjungates in Chagas disease 385:430 To better understand the role of glycoconjungates in Chagas disease, we performed the molecular characterization of the O-linked chains from mucins and glycoinositolphospholipids (GIPLs) of the Silvio X10 clone 1 strain. 27556227 5 20 theme distal 954:959 arg1 mannose 961:967 the third distal mannose 944:967 the third distal mannose from inositol 944:981 GIPLs analysis showed that the lipidic portion is exclusively composed of ceramide and the PI-oligossacharidic portion contains the Man4(AEP)GlcN-Ins-PO4 core, substituted by ethanolamine-phosphate (EtNP) on the third distal mannose from inositol, which may or may not have a terminal β Galf unity. 27556227 5 21 theme GIPLs 736:740 arg1 analysis 742:749 GIPLs analysis 736:749 GIPLs analysis 736:749 GIPLs analysis showed that the lipidic portion is exclusively composed of ceramide and the PI-oligossacharidic portion contains the Man4(AEP)GlcN-Ins-PO4 core, substituted by ethanolamine-phosphate (EtNP) on the third distal mannose from inositol, which may or may not have a terminal β Galf unity. 27556227 4 22 theme O-4 718:720 arg1 position 670:677 the O-4 position 662:677 the O-4 position of the α-N-acetylglucosamine (α-GlcNAc)O-4 in Tc-mucins 662:733 We demonstrated the presence of a β-galactofuranose (β-Galf) unity linked to the O-4 position of the α-N-acetylglucosamine (α-GlcNAc)O-4 in Tc-mucins. 27556227 2 23 dep T. 256:257 arg1 cruzi 259:263 cruzi 259:263 cruzi 259:263 One of the main obstacles to the treatment of Chagas disease is the genetic and phenotypical variance displayed by T. cruzi strains, resulting in differences in morphology, virulence, pathogenicity and drug susceptibility. 27556227 6 24 theme Silvio 1083:1088 arg1 strain 1096:1101 the Silvio X10/1 strain 1079:1101 the Silvio X10/1 strain 1079:1101 These results confirm the classification of the Silvio X10/1 strain in group T. cruzi I. Again, it is noted that the study of T. cruzi surface glycoconjugates confirm the molecular results and the hypothesis that surface glycoconjugates may be interesting biomarker for the differentiation of trypanosomatid strains. 27556227 3 25 theme clone 569:573 arg1 strain 577:582 the Silvio X10 clone 1 strain 554:582 the Silvio X10 clone 1 strain 554:582 To better understand the role of glycoconjungates in Chagas disease, we performed the molecular characterization of the O-linked chains from mucins and glycoinositolphospholipids (GIPLs) of the Silvio X10 clone 1 strain. 27556227 5 26 theme Man4 868:871 arg1 core 890:893 the Man4(AEP)GlcN-Ins-PO4 core 864:893 the Man4(AEP)GlcN-Ins-PO4 core 864:893 GIPLs analysis showed that the lipidic portion is exclusively composed of ceramide and the PI-oligossacharidic portion contains the Man4(AEP)GlcN-Ins-PO4 core, substituted by ethanolamine-phosphate (EtNP) on the third distal mannose from inositol, which may or may not have a terminal β Galf unity. 27556227 4 27 theme α-N-acetylglucosamine 686:706 arg1 O-4 718:720 the α-N-acetylglucosamine (α-GlcNAc)O-4 682:720 the α-N-acetylglucosamine (α-GlcNAc)O-4 682:720 We demonstrated the presence of a β-galactofuranose (β-Galf) unity linked to the O-4 position of the α-N-acetylglucosamine (α-GlcNAc)O-4 in Tc-mucins. 27556227 5 28 theme lipidic 767:773 arg1 portion 775:781 the lipidic portion 763:781 the lipidic portion 763:781 GIPLs analysis showed that the lipidic portion is exclusively composed of ceramide and the PI-oligossacharidic portion contains the Man4(AEP)GlcN-Ins-PO4 core, substituted by ethanolamine-phosphate (EtNP) on the third distal mannose from inositol, which may or may not have a terminal β Galf unity. 27556227 3 29 theme molecular 450:458 arg1 characterization 460:475 the molecular characterization 446:475 the molecular characterization of the O-linked chains from mucins and glycoinositolphospholipids (GIPLs) of the Silvio X10 clone 1 strain 446:582 To better understand the role of glycoconjungates in Chagas disease, we performed the molecular characterization of the O-linked chains from mucins and glycoinositolphospholipids (GIPLs) of the Silvio X10 clone 1 strain. 27556227 5 30 theme β 1021:1021 arg1 unity 1028:1032 a terminal β Galf unity 1010:1032 a terminal β Galf unity 1010:1032 GIPLs analysis showed that the lipidic portion is exclusively composed of ceramide and the PI-oligossacharidic portion contains the Man4(AEP)GlcN-Ins-PO4 core, substituted by ethanolamine-phosphate (EtNP) on the third distal mannose from inositol, which may or may not have a terminal β Galf unity. 27556227 3 31 theme Silvio 558:563 arg1 strain 577:582 the Silvio X10 clone 1 strain 554:582 the Silvio X10 clone 1 strain 554:582 To better understand the role of glycoconjungates in Chagas disease, we performed the molecular characterization of the O-linked chains from mucins and glycoinositolphospholipids (GIPLs) of the Silvio X10 clone 1 strain. 27556227 0 32 theme chemical 31:38 arg1 structure 40:48 the chemical structure 27:48 the chemical structure of glycoconjugates from Trypanosoma cruzi TcI genotype 27:103 Expanding the knowledge of the chemical structure of glycoconjugates from Trypanosoma cruzi TcI genotype. 27556227 3 33 theme chains 493:498 arg1 characterization 460:475 the molecular characterization 446:475 the molecular characterization of the O-linked chains from mucins and glycoinositolphospholipids (GIPLs) of the Silvio X10 clone 1 strain 446:582 To better understand the role of glycoconjungates in Chagas disease, we performed the molecular characterization of the O-linked chains from mucins and glycoinositolphospholipids (GIPLs) of the Silvio X10 clone 1 strain. 27556227 0 34 from Trypanosoma 74:84 arg1 glycoconjugates 53:67 glycoconjugates 53:67 glycoconjugates from Trypanosoma cruzi TcI genotype 53:103 Expanding the knowledge of the chemical structure of glycoconjugates from Trypanosoma cruzi TcI genotype. 27556227 0 34 from Trypanosoma 74:84 arg1 structure 40:48 the chemical structure 27:48 the chemical structure of glycoconjugates from Trypanosoma cruzi TcI genotype 27:103 Expanding the knowledge of the chemical structure of glycoconjugates from Trypanosoma cruzi TcI genotype. 27556227 2 35 theme phenotypical 221:232 arg1 obstacles 157:165 the main obstacles 148:165 the main obstacles to the treatment of Chagas disease 148:200 One of the main obstacles to the treatment of Chagas disease is the genetic and phenotypical variance displayed by T. cruzi strains, resulting in differences in morphology, virulence, pathogenicity and drug susceptibility. 27556227 2 35 theme phenotypical 221:232 arg1 One 141:143 One 141:143 One 141:143 One of the main obstacles to the treatment of Chagas disease is the genetic and phenotypical variance displayed by T. cruzi strains, resulting in differences in morphology, virulence, pathogenicity and drug susceptibility. 27556227 2 35 theme phenotypical 221:232 arg1 variance 234:241 the genetic and phenotypical variance 205:241 the genetic and phenotypical variance displayed by T. cruzi strains 205:271 One of the main obstacles to the treatment of Chagas disease is the genetic and phenotypical variance displayed by T. cruzi strains, resulting in differences in morphology, virulence, pathogenicity and drug susceptibility. 27556227 4 36 theme β-Galf 638:643 arg1 unity 646:650 a β-galactofuranose (β-Galf) unity 617:650 a β-galactofuranose (β-Galf) unity linked to the O-4 position of the α-N-acetylglucosamine (α-GlcNAc)O-4 in Tc-mucins 617:733 We demonstrated the presence of a β-galactofuranose (β-Galf) unity linked to the O-4 position of the α-N-acetylglucosamine (α-GlcNAc)O-4 in Tc-mucins. 27556227 6 37 theme surface 1170:1176 arg1 glycoconjugates 1178:1192 T. cruzi surface glycoconjugates 1161:1192 T. cruzi surface glycoconjugates 1161:1192 These results confirm the classification of the Silvio X10/1 strain in group T. cruzi I. Again, it is noted that the study of T. cruzi surface glycoconjugates confirm the molecular results and the hypothesis that surface glycoconjugates may be interesting biomarker for the differentiation of trypanosomatid strains. 27556227 6 38 theme molecular 1206:1214 arg1 results 1216:1222 the molecular results 1202:1222 the molecular results 1202:1222 These results confirm the classification of the Silvio X10/1 strain in group T. cruzi I. Again, it is noted that the study of T. cruzi surface glycoconjugates confirm the molecular results and the hypothesis that surface glycoconjugates may be interesting biomarker for the differentiation of trypanosomatid strains. 27556227 6 39 theme surface 1248:1254 arg1 glycoconjugates 1256:1270 surface glycoconjugates 1248:1270 surface glycoconjugates 1248:1270 These results confirm the classification of the Silvio X10/1 strain in group T. cruzi I. Again, it is noted that the study of T. cruzi surface glycoconjugates confirm the molecular results and the hypothesis that surface glycoconjugates may be interesting biomarker for the differentiation of trypanosomatid strains. 27556227 4 40 attach linked 652:657 arg1 position 670:677 the O-4 position 662:677 the O-4 position of the α-N-acetylglucosamine (α-GlcNAc)O-4 in Tc-mucins 662:733 We demonstrated the presence of a β-galactofuranose (β-Galf) unity linked to the O-4 position of the α-N-acetylglucosamine (α-GlcNAc)O-4 in Tc-mucins. 27556227 4 40 attach linked 652:657 arg2 unity 646:650 a β-galactofuranose (β-Galf) unity 617:650 a β-galactofuranose (β-Galf) unity linked to the O-4 position of the α-N-acetylglucosamine (α-GlcNAc)O-4 in Tc-mucins 617:733 We demonstrated the presence of a β-galactofuranose (β-Galf) unity linked to the O-4 position of the α-N-acetylglucosamine (α-GlcNAc)O-4 in Tc-mucins. 27556227 5 41 theme PI-oligossacharidic 827:845 arg1 portion 847:853 the PI-oligossacharidic portion 823:853 the PI-oligossacharidic portion 823:853 GIPLs analysis showed that the lipidic portion is exclusively composed of ceramide and the PI-oligossacharidic portion contains the Man4(AEP)GlcN-Ins-PO4 core, substituted by ethanolamine-phosphate (EtNP) on the third distal mannose from inositol, which may or may not have a terminal β Galf unity. 27556227 5 42 contain have 1005:1008 arg2 unity 1028:1032 a terminal β Galf unity 1010:1032 a terminal β Galf unity 1010:1032 GIPLs analysis showed that the lipidic portion is exclusively composed of ceramide and the PI-oligossacharidic portion contains the Man4(AEP)GlcN-Ins-PO4 core, substituted by ethanolamine-phosphate (EtNP) on the third distal mannose from inositol, which may or may not have a terminal β Galf unity. 27556227 5 42 contain have 1005:1008 arg1 core 890:893 the Man4(AEP)GlcN-Ins-PO4 core 864:893 the Man4(AEP)GlcN-Ins-PO4 core 864:893 GIPLs analysis showed that the lipidic portion is exclusively composed of ceramide and the PI-oligossacharidic portion contains the Man4(AEP)GlcN-Ins-PO4 core, substituted by ethanolamine-phosphate (EtNP) on the third distal mannose from inositol, which may or may not have a terminal β Galf unity. 27556227 2 43 theme obstacles 157:165 arg1 obstacles 157:165 the main obstacles 148:165 the main obstacles to the treatment of Chagas disease 148:200 One of the main obstacles to the treatment of Chagas disease is the genetic and phenotypical variance displayed by T. cruzi strains, resulting in differences in morphology, virulence, pathogenicity and drug susceptibility. 27556227 2 43 theme obstacles 157:165 arg1 variance 234:241 the genetic and phenotypical variance 205:241 the genetic and phenotypical variance displayed by T. cruzi strains 205:271 One of the main obstacles to the treatment of Chagas disease is the genetic and phenotypical variance displayed by T. cruzi strains, resulting in differences in morphology, virulence, pathogenicity and drug susceptibility. 27556227 2 43 theme obstacles 157:165 arg1 One 141:143 One 141:143 One 141:143 One of the main obstacles to the treatment of Chagas disease is the genetic and phenotypical variance displayed by T. cruzi strains, resulting in differences in morphology, virulence, pathogenicity and drug susceptibility. 27556227 2 44 theme genetic 209:215 arg1 obstacles 157:165 the main obstacles 148:165 the main obstacles to the treatment of Chagas disease 148:200 One of the main obstacles to the treatment of Chagas disease is the genetic and phenotypical variance displayed by T. cruzi strains, resulting in differences in morphology, virulence, pathogenicity and drug susceptibility. 27556227 2 44 theme genetic 209:215 arg1 One 141:143 One 141:143 One 141:143 One of the main obstacles to the treatment of Chagas disease is the genetic and phenotypical variance displayed by T. cruzi strains, resulting in differences in morphology, virulence, pathogenicity and drug susceptibility. 27556227 2 44 theme genetic 209:215 arg1 variance 234:241 the genetic and phenotypical variance 205:241 the genetic and phenotypical variance displayed by T. cruzi strains 205:271 One of the main obstacles to the treatment of Chagas disease is the genetic and phenotypical variance displayed by T. cruzi strains, resulting in differences in morphology, virulence, pathogenicity and drug susceptibility. 27556227 3 45 theme O-linked 484:491 arg1 chains 493:498 the O-linked chains 480:498 the O-linked chains from mucins and glycoinositolphospholipids (GIPLs) of the Silvio X10 clone 1 strain 480:582 To better understand the role of glycoconjungates in Chagas disease, we performed the molecular characterization of the O-linked chains from mucins and glycoinositolphospholipids (GIPLs) of the Silvio X10 clone 1 strain. 27556227 0 46 theme structure 40:48 arg1 knowledge 14:22 the knowledge 10:22 the knowledge of the chemical structure of glycoconjugates from Trypanosoma cruzi TcI genotype 10:103 Expanding the knowledge of the chemical structure of glycoconjugates from Trypanosoma cruzi TcI genotype. 27556227 3 47 theme strain 577:582 arg1 mucins 505:510 mucins 505:510 mucins 505:510 To better understand the role of glycoconjungates in Chagas disease, we performed the molecular characterization of the O-linked chains from mucins and glycoinositolphospholipids (GIPLs) of the Silvio X10 clone 1 strain. 27556227 3 47 theme strain 577:582 arg1 GIPLs 544:548 GIPLs 544:548 GIPLs 544:548 To better understand the role of glycoconjungates in Chagas disease, we performed the molecular characterization of the O-linked chains from mucins and glycoinositolphospholipids (GIPLs) of the Silvio X10 clone 1 strain. 27556227 3 47 theme strain 577:582 arg1 glycoinositolphospholipids 516:541 glycoinositolphospholipids 516:541 glycoinositolphospholipids 516:541 To better understand the role of glycoconjungates in Chagas disease, we performed the molecular characterization of the O-linked chains from mucins and glycoinositolphospholipids (GIPLs) of the Silvio X10 clone 1 strain. 27556227 1 48 theme taxonomic 122:130 arg1 studies 132:138 taxonomic studies 122:138 taxonomic studies 122:138 Contribution to taxonomic studies. 27556227 3 49 link O-linked 484:491 arg1 chains 493:498 the O-linked chains 480:498 the O-linked chains from mucins and glycoinositolphospholipids (GIPLs) of the Silvio X10 clone 1 strain 480:582 To better understand the role of glycoconjungates in Chagas disease, we performed the molecular characterization of the O-linked chains from mucins and glycoinositolphospholipids (GIPLs) of the Silvio X10 clone 1 strain. 27556227 2 50 theme disease 194:200 arg1 treatment 174:182 the treatment 170:182 the treatment of Chagas disease 170:200 One of the main obstacles to the treatment of Chagas disease is the genetic and phenotypical variance displayed by T. cruzi strains, resulting in differences in morphology, virulence, pathogenicity and drug susceptibility. 27556227 2 51 theme T. 256:257 arg1 strains 265:271 T. cruzi strains 256:271 T. cruzi strains 256:271 One of the main obstacles to the treatment of Chagas disease is the genetic and phenotypical variance displayed by T. cruzi strains, resulting in differences in morphology, virulence, pathogenicity and drug susceptibility. 27556227 3 52 from characterization 460:475 arg1 mucins 505:510 mucins 505:510 mucins 505:510 To better understand the role of glycoconjungates in Chagas disease, we performed the molecular characterization of the O-linked chains from mucins and glycoinositolphospholipids (GIPLs) of the Silvio X10 clone 1 strain. 27556227 3 52 from characterization 460:475 arg1 GIPLs 544:548 GIPLs 544:548 GIPLs 544:548 To better understand the role of glycoconjungates in Chagas disease, we performed the molecular characterization of the O-linked chains from mucins and glycoinositolphospholipids (GIPLs) of the Silvio X10 clone 1 strain. 27556227 3 52 from characterization 460:475 arg1 glycoinositolphospholipids 516:541 glycoinositolphospholipids 516:541 glycoinositolphospholipids 516:541 To better understand the role of glycoconjungates in Chagas disease, we performed the molecular characterization of the O-linked chains from mucins and glycoinositolphospholipids (GIPLs) of the Silvio X10 clone 1 strain. 27556227 4 53 theme α-GlcNAc 709:716 arg1 O-4 718:720 the α-N-acetylglucosamine (α-GlcNAc)O-4 682:720 the α-N-acetylglucosamine (α-GlcNAc)O-4 682:720 We demonstrated the presence of a β-galactofuranose (β-Galf) unity linked to the O-4 position of the α-N-acetylglucosamine (α-GlcNAc)O-4 in Tc-mucins. 27556227 6 54 theme strain 1096:1101 arg1 classification 1061:1074 the classification 1057:1074 the classification of the Silvio X10/1 strain 1057:1101 These results confirm the classification of the Silvio X10/1 strain in group T. cruzi I. Again, it is noted that the study of T. cruzi surface glycoconjugates confirm the molecular results and the hypothesis that surface glycoconjugates may be interesting biomarker for the differentiation of trypanosomatid strains. 27556227 6 55 dep T. 1161:1162 arg1 cruzi 1164:1168 cruzi 1164:1168 cruzi 1164:1168 These results confirm the classification of the Silvio X10/1 strain in group T. cruzi I. Again, it is noted that the study of T. cruzi surface glycoconjugates confirm the molecular results and the hypothesis that surface glycoconjugates may be interesting biomarker for the differentiation of trypanosomatid strains. 27556227 0 56 from genotype 96:103 arg1 glycoconjugates 53:67 glycoconjugates 53:67 glycoconjugates from Trypanosoma cruzi TcI genotype 53:103 Expanding the knowledge of the chemical structure of glycoconjugates from Trypanosoma cruzi TcI genotype. 27556227 0 56 from genotype 96:103 arg1 structure 40:48 the chemical structure 27:48 the chemical structure of glycoconjugates from Trypanosoma cruzi TcI genotype 27:103 Expanding the knowledge of the chemical structure of glycoconjugates from Trypanosoma cruzi TcI genotype. 27556227 5 57 theme Galf 1023:1026 arg1 unity 1028:1032 a terminal β Galf unity 1010:1032 a terminal β Galf unity 1010:1032 GIPLs analysis showed that the lipidic portion is exclusively composed of ceramide and the PI-oligossacharidic portion contains the Man4(AEP)GlcN-Ins-PO4 core, substituted by ethanolamine-phosphate (EtNP) on the third distal mannose from inositol, which may or may not have a terminal β Galf unity. 27556227 5 58 from ethanolamine-phosphate 911:932 arg1 mannose 961:967 the third distal mannose 944:967 the third distal mannose from inositol 944:981 GIPLs analysis showed that the lipidic portion is exclusively composed of ceramide and the PI-oligossacharidic portion contains the Man4(AEP)GlcN-Ins-PO4 core, substituted by ethanolamine-phosphate (EtNP) on the third distal mannose from inositol, which may or may not have a terminal β Galf unity. 27556227 6 59 theme strains 1343:1349 arg1 differentiation 1309:1323 the differentiation 1305:1323 the differentiation of trypanosomatid strains 1305:1349 These results confirm the classification of the Silvio X10/1 strain in group T. cruzi I. Again, it is noted that the study of T. cruzi surface glycoconjugates confirm the molecular results and the hypothesis that surface glycoconjugates may be interesting biomarker for the differentiation of trypanosomatid strains. 27556227 5 60 theme terminal 1012:1019 arg1 unity 1028:1032 a terminal β Galf unity 1010:1032 a terminal β Galf unity 1010:1032 GIPLs analysis showed that the lipidic portion is exclusively composed of ceramide and the PI-oligossacharidic portion contains the Man4(AEP)GlcN-Ins-PO4 core, substituted by ethanolamine-phosphate (EtNP) on the third distal mannose from inositol, which may or may not have a terminal β Galf unity. 27556227 4 61 theme β-galactofuranose 619:635 arg1 unity 646:650 a β-galactofuranose (β-Galf) unity 617:650 a β-galactofuranose (β-Galf) unity linked to the O-4 position of the α-N-acetylglucosamine (α-GlcNAc)O-4 in Tc-mucins 617:733 We demonstrated the presence of a β-galactofuranose (β-Galf) unity linked to the O-4 position of the α-N-acetylglucosamine (α-GlcNAc)O-4 in Tc-mucins. 27556227 4 62 theme O-4 666:668 arg1 position 670:677 the O-4 position 662:677 the O-4 position of the α-N-acetylglucosamine (α-GlcNAc)O-4 in Tc-mucins 662:733 We demonstrated the presence of a β-galactofuranose (β-Galf) unity linked to the O-4 position of the α-N-acetylglucosamine (α-GlcNAc)O-4 in Tc-mucins. 27556227 0 63 theme glycoconjugates 53:67 arg1 structure 40:48 the chemical structure 27:48 the chemical structure of glycoconjugates from Trypanosoma cruzi TcI genotype 27:103 Expanding the knowledge of the chemical structure of glycoconjugates from Trypanosoma cruzi TcI genotype. 27556227 3 64 from role 389:392 arg1 disease 424:430 Chagas disease 417:430 Chagas disease 417:430 To better understand the role of glycoconjungates in Chagas disease, we performed the molecular characterization of the O-linked chains from mucins and glycoinositolphospholipids (GIPLs) of the Silvio X10 clone 1 strain. 27556227 6 65 dep group 1106:1110 arg1 I. 1121:1122 I. 1121:1122 I. 1121:1122 These results confirm the classification of the Silvio X10/1 strain in group T. cruzi I. Again, it is noted that the study of T. cruzi surface glycoconjugates confirm the molecular results and the hypothesis that surface glycoconjugates may be interesting biomarker for the differentiation of trypanosomatid strains. 27556227 6 65 dep group 1106:1110 arg1 T. 1112:1113 T. 1112:1113 T. 1112:1113 These results confirm the classification of the Silvio X10/1 strain in group T. cruzi I. Again, it is noted that the study of T. cruzi surface glycoconjugates confirm the molecular results and the hypothesis that surface glycoconjugates may be interesting biomarker for the differentiation of trypanosomatid strains. 27556227 5 66 theme AEP 873:875 arg1 core 890:893 the Man4(AEP)GlcN-Ins-PO4 core 864:893 the Man4(AEP)GlcN-Ins-PO4 core 864:893 GIPLs analysis showed that the lipidic portion is exclusively composed of ceramide and the PI-oligossacharidic portion contains the Man4(AEP)GlcN-Ins-PO4 core, substituted by ethanolamine-phosphate (EtNP) on the third distal mannose from inositol, which may or may not have a terminal β Galf unity. 27556227 2 67 from differences 287:297 arg1 pathogenicity 325:337 pathogenicity 325:337 pathogenicity 325:337 One of the main obstacles to the treatment of Chagas disease is the genetic and phenotypical variance displayed by T. cruzi strains, resulting in differences in morphology, virulence, pathogenicity and drug susceptibility. 27556227 2 67 from differences 287:297 arg1 susceptibility 348:361 drug susceptibility 343:361 drug susceptibility 343:361 One of the main obstacles to the treatment of Chagas disease is the genetic and phenotypical variance displayed by T. cruzi strains, resulting in differences in morphology, virulence, pathogenicity and drug susceptibility. 27556227 2 67 from differences 287:297 arg1 virulence 314:322 virulence 314:322 virulence 314:322 One of the main obstacles to the treatment of Chagas disease is the genetic and phenotypical variance displayed by T. cruzi strains, resulting in differences in morphology, virulence, pathogenicity and drug susceptibility. 27556227 2 67 from differences 287:297 arg1 morphology 302:311 morphology 302:311 morphology 302:311 One of the main obstacles to the treatment of Chagas disease is the genetic and phenotypical variance displayed by T. cruzi strains, resulting in differences in morphology, virulence, pathogenicity and drug susceptibility. 27453399 3 0 theme aglycone 668:675 arg1 Ser/Thr 688:694 Ser/Thr 688:694 Ser/Thr 688:694 Mucin-related glycopeptides incorporating these motifs were recognized by the monoclonal antibody (mAb) scFv-SM3, with activities depending on both the hydroxylation pattern (Glc/Gal/GlcNAc/GalNAc) of the sp(2)-iminosugar and the peptide aglycone structure (Ser/Thr). 27453399 3 0 theme aglycone 668:675 arg1 structure 677:685 the peptide aglycone structure 656:685 the peptide aglycone structure (Ser/Thr) 656:695 Mucin-related glycopeptides incorporating these motifs were recognized by the monoclonal antibody (mAb) scFv-SM3, with activities depending on both the hydroxylation pattern (Glc/Gal/GlcNAc/GalNAc) of the sp(2)-iminosugar and the peptide aglycone structure (Ser/Thr). 27453399 1 1 theme pseudoanomeric 194:207 arg1 linkage 209:215 an α-O-linked pseudoanomeric linkage 180:215 an α-O-linked pseudoanomeric linkage 180:215 The first examples of amino acid (Ser/Thr)-sp(2)-iminosugar glycomimetic conjugates featuring an α-O-linked pseudoanomeric linkage are reported. 27453399 2 2 theme synthetic 239:247 arg1 step 249:252 The key synthetic step 231:252 The key synthetic step 231:252 The key synthetic step involves the completely diastereoselective α-glycosylation of Ser/Thr due to strong stereoelectronic and conformational bias imposed by the bicyclic sp(2)-iminosugar scaffold. 27453399 0 3 with -Iminosugars 32:43 arg1 Affinity 50:57 Affinity 50:57 Affinity for an anti-MUC1 Antibody 50:83 Tn Antigen Mimics Based on sp(2)-Iminosugars with Affinity for an anti-MUC1 Antibody. 27453399 2 4 theme key 235:237 arg1 step 249:252 The key synthetic step 231:252 The key synthetic step 231:252 The key synthetic step involves the completely diastereoselective α-glycosylation of Ser/Thr due to strong stereoelectronic and conformational bias imposed by the bicyclic sp(2)-iminosugar scaffold. 27453399 3 5 theme antibody 519:526 arg1 scFv-SM3 534:541 the monoclonal antibody (mAb) scFv-SM3 504:541 the monoclonal antibody (mAb) scFv-SM3 504:541 Mucin-related glycopeptides incorporating these motifs were recognized by the monoclonal antibody (mAb) scFv-SM3, with activities depending on both the hydroxylation pattern (Glc/Gal/GlcNAc/GalNAc) of the sp(2)-iminosugar and the peptide aglycone structure (Ser/Thr). 27453399 0 6 theme anti-MUC1 66:74 arg1 Antibody 76:83 an anti-MUC1 Antibody 63:83 an anti-MUC1 Antibody 63:83 Tn Antigen Mimics Based on sp(2)-Iminosugars with Affinity for an anti-MUC1 Antibody. 27453399 2 7 theme -iminosugar 408:418 arg1 scaffold 420:427 the bicyclic sp(2)-iminosugar scaffold 390:427 the bicyclic sp(2)-iminosugar scaffold 390:427 The key synthetic step involves the completely diastereoselective α-glycosylation of Ser/Thr due to strong stereoelectronic and conformational bias imposed by the bicyclic sp(2)-iminosugar scaffold. 27453399 3 8 theme monoclonal 508:517 arg1 mAb 529:531 mAb 529:531 mAb 529:531 Mucin-related glycopeptides incorporating these motifs were recognized by the monoclonal antibody (mAb) scFv-SM3, with activities depending on both the hydroxylation pattern (Glc/Gal/GlcNAc/GalNAc) of the sp(2)-iminosugar and the peptide aglycone structure (Ser/Thr). 27453399 3 8 theme monoclonal 508:517 arg1 antibody 519:526 monoclonal antibody 508:526 the monoclonal antibody (mAb) scFv-SM3 504:541 Mucin-related glycopeptides incorporating these motifs were recognized by the monoclonal antibody (mAb) scFv-SM3, with activities depending on both the hydroxylation pattern (Glc/Gal/GlcNAc/GalNAc) of the sp(2)-iminosugar and the peptide aglycone structure (Ser/Thr). 27453399 1 9 link α-O-linked 183:192 arg1 linkage 209:215 an α-O-linked pseudoanomeric linkage 180:215 an α-O-linked pseudoanomeric linkage 180:215 The first examples of amino acid (Ser/Thr)-sp(2)-iminosugar glycomimetic conjugates featuring an α-O-linked pseudoanomeric linkage are reported. 27453399 3 10 dep recognized 490:499 arg1 with 544:547 with 544:547 with 544:547 Mucin-related glycopeptides incorporating these motifs were recognized by the monoclonal antibody (mAb) scFv-SM3, with activities depending on both the hydroxylation pattern (Glc/Gal/GlcNAc/GalNAc) of the sp(2)-iminosugar and the peptide aglycone structure (Ser/Thr). 27453399 2 11 theme conformational 359:372 arg1 bias 374:377 strong stereoelectronic and conformational bias 331:377 strong stereoelectronic and conformational bias imposed by the bicyclic sp(2)-iminosugar scaffold 331:427 The key synthetic step involves the completely diastereoselective α-glycosylation of Ser/Thr due to strong stereoelectronic and conformational bias imposed by the bicyclic sp(2)-iminosugar scaffold. 27453399 0 12 theme Tn 0:1 arg1 Antigen 3:9 Tn Antigen 0:9 Tn Antigen 0:9 Tn Antigen Mimics Based on sp(2)-Iminosugars with Affinity for an anti-MUC1 Antibody. 27453399 2 13 theme sp 403:404 arg1 scaffold 420:427 the bicyclic sp(2)-iminosugar scaffold 390:427 the bicyclic sp(2)-iminosugar scaffold 390:427 The key synthetic step involves the completely diastereoselective α-glycosylation of Ser/Thr due to strong stereoelectronic and conformational bias imposed by the bicyclic sp(2)-iminosugar scaffold. 27453399 2 14 theme bicyclic 394:401 arg1 scaffold 420:427 the bicyclic sp(2)-iminosugar scaffold 390:427 the bicyclic sp(2)-iminosugar scaffold 390:427 The key synthetic step involves the completely diastereoselective α-glycosylation of Ser/Thr due to strong stereoelectronic and conformational bias imposed by the bicyclic sp(2)-iminosugar scaffold. 27453399 0 15 theme sp 27:28 arg1 -Iminosugars 32:43 sp(2)-Iminosugars 27:43 sp(2)-Iminosugars with Affinity for an anti-MUC1 Antibody 27:83 Tn Antigen Mimics Based on sp(2)-Iminosugars with Affinity for an anti-MUC1 Antibody. 27453399 3 16 theme sp 635:636 arg1 -iminosugar 640:650 the sp(2)-iminosugar 631:650 the sp(2)-iminosugar 631:650 Mucin-related glycopeptides incorporating these motifs were recognized by the monoclonal antibody (mAb) scFv-SM3, with activities depending on both the hydroxylation pattern (Glc/Gal/GlcNAc/GalNAc) of the sp(2)-iminosugar and the peptide aglycone structure (Ser/Thr). 27453399 3 17 gly glycopeptides 444:456 arg2 glycopeptides 444:456 Mucin-related glycopeptides 430:456 Mucin-related glycopeptides incorporating these motifs 430:483 Mucin-related glycopeptides incorporating these motifs were recognized by the monoclonal antibody (mAb) scFv-SM3, with activities depending on both the hydroxylation pattern (Glc/Gal/GlcNAc/GalNAc) of the sp(2)-iminosugar and the peptide aglycone structure (Ser/Thr). 27453399 1 18 theme -iminosugar 134:144 arg1 conjugates 159:168 amino acid (Ser/Thr)-sp(2)-iminosugar glycomimetic conjugates 108:168 amino acid (Ser/Thr)-sp(2)-iminosugar glycomimetic conjugates featuring an α-O-linked pseudoanomeric linkage 108:215 The first examples of amino acid (Ser/Thr)-sp(2)-iminosugar glycomimetic conjugates featuring an α-O-linked pseudoanomeric linkage are reported. 27453399 1 19 theme glycomimetic 146:157 arg1 conjugates 159:168 amino acid (Ser/Thr)-sp(2)-iminosugar glycomimetic conjugates 108:168 amino acid (Ser/Thr)-sp(2)-iminosugar glycomimetic conjugates featuring an α-O-linked pseudoanomeric linkage 108:215 The first examples of amino acid (Ser/Thr)-sp(2)-iminosugar glycomimetic conjugates featuring an α-O-linked pseudoanomeric linkage are reported. 27453399 2 20 theme Ser/Thr 316:322 arg1 α-glycosylation 297:311 the completely diastereoselective α-glycosylation 263:311 the completely diastereoselective α-glycosylation of Ser/Thr due to strong stereoelectronic and conformational bias imposed by the bicyclic sp(2)-iminosugar scaffold 263:427 The key synthetic step involves the completely diastereoselective α-glycosylation of Ser/Thr due to strong stereoelectronic and conformational bias imposed by the bicyclic sp(2)-iminosugar scaffold. 27453399 1 21 theme amino 108:112 arg1 acid 114:117 amino acid 108:117 amino acid 108:117 The first examples of amino acid (Ser/Thr)-sp(2)-iminosugar glycomimetic conjugates featuring an α-O-linked pseudoanomeric linkage are reported. 27453399 3 22 theme -iminosugar 640:650 arg1 pattern 596:602 the hydroxylation pattern 578:602 the hydroxylation pattern (Glc/Gal/GlcNAc/GalNAc) of the sp(2)-iminosugar 578:650 Mucin-related glycopeptides incorporating these motifs were recognized by the monoclonal antibody (mAb) scFv-SM3, with activities depending on both the hydroxylation pattern (Glc/Gal/GlcNAc/GalNAc) of the sp(2)-iminosugar and the peptide aglycone structure (Ser/Thr). 27453399 3 22 theme -iminosugar 640:650 arg1 Ser/Thr 688:694 Ser/Thr 688:694 Ser/Thr 688:694 Mucin-related glycopeptides incorporating these motifs were recognized by the monoclonal antibody (mAb) scFv-SM3, with activities depending on both the hydroxylation pattern (Glc/Gal/GlcNAc/GalNAc) of the sp(2)-iminosugar and the peptide aglycone structure (Ser/Thr). 27453399 3 22 theme -iminosugar 640:650 arg1 structure 677:685 the peptide aglycone structure 656:685 the peptide aglycone structure (Ser/Thr) 656:695 Mucin-related glycopeptides incorporating these motifs were recognized by the monoclonal antibody (mAb) scFv-SM3, with activities depending on both the hydroxylation pattern (Glc/Gal/GlcNAc/GalNAc) of the sp(2)-iminosugar and the peptide aglycone structure (Ser/Thr). 27453399 3 22 theme -iminosugar 640:650 arg1 Glc/Gal/GlcNAc/GalNAc 605:625 Glc/Gal/GlcNAc/GalNAc 605:625 Glc/Gal/GlcNAc/GalNAc 605:625 Mucin-related glycopeptides incorporating these motifs were recognized by the monoclonal antibody (mAb) scFv-SM3, with activities depending on both the hydroxylation pattern (Glc/Gal/GlcNAc/GalNAc) of the sp(2)-iminosugar and the peptide aglycone structure (Ser/Thr). 27453399 1 23 dep -iminosugar 134:144 arg1 acid 114:117 amino acid 108:117 amino acid 108:117 The first examples of amino acid (Ser/Thr)-sp(2)-iminosugar glycomimetic conjugates featuring an α-O-linked pseudoanomeric linkage are reported. 27453399 1 24 theme first 90:94 arg1 examples 96:103 The first examples 86:103 The first examples of amino acid (Ser/Thr)-sp(2)-iminosugar glycomimetic conjugates featuring an α-O-linked pseudoanomeric linkage 86:215 The first examples of amino acid (Ser/Thr)-sp(2)-iminosugar glycomimetic conjugates featuring an α-O-linked pseudoanomeric linkage are reported. 27453399 1 25 theme conjugates 159:168 arg1 examples 96:103 The first examples 86:103 The first examples of amino acid (Ser/Thr)-sp(2)-iminosugar glycomimetic conjugates featuring an α-O-linked pseudoanomeric linkage 86:215 The first examples of amino acid (Ser/Thr)-sp(2)-iminosugar glycomimetic conjugates featuring an α-O-linked pseudoanomeric linkage are reported. 27453399 2 26 gly α-glycosylation 297:311 arg1 Ser/Thr 316:322 Ser/Thr 316:322 Ser/Thr 316:322 The key synthetic step involves the completely diastereoselective α-glycosylation of Ser/Thr due to strong stereoelectronic and conformational bias imposed by the bicyclic sp(2)-iminosugar scaffold. 27453399 0 27 dep Mimics 11:16 arg1 Based 18:22 Based 18:22 Mimics Based on sp(2)-Iminosugars with Affinity for an anti-MUC1 Antibody 11:83 Tn Antigen Mimics Based on sp(2)-Iminosugars with Affinity for an anti-MUC1 Antibody. 27453399 2 28 theme diastereoselective 278:295 arg1 α-glycosylation 297:311 the completely diastereoselective α-glycosylation 263:311 the completely diastereoselective α-glycosylation of Ser/Thr due to strong stereoelectronic and conformational bias imposed by the bicyclic sp(2)-iminosugar scaffold 263:427 The key synthetic step involves the completely diastereoselective α-glycosylation of Ser/Thr due to strong stereoelectronic and conformational bias imposed by the bicyclic sp(2)-iminosugar scaffold. 27453399 3 29 theme hydroxylation 582:594 arg1 pattern 596:602 the hydroxylation pattern 578:602 the hydroxylation pattern (Glc/Gal/GlcNAc/GalNAc) of the sp(2)-iminosugar 578:650 Mucin-related glycopeptides incorporating these motifs were recognized by the monoclonal antibody (mAb) scFv-SM3, with activities depending on both the hydroxylation pattern (Glc/Gal/GlcNAc/GalNAc) of the sp(2)-iminosugar and the peptide aglycone structure (Ser/Thr). 27453399 3 29 theme hydroxylation 582:594 arg1 Glc/Gal/GlcNAc/GalNAc 605:625 Glc/Gal/GlcNAc/GalNAc 605:625 Glc/Gal/GlcNAc/GalNAc 605:625 Mucin-related glycopeptides incorporating these motifs were recognized by the monoclonal antibody (mAb) scFv-SM3, with activities depending on both the hydroxylation pattern (Glc/Gal/GlcNAc/GalNAc) of the sp(2)-iminosugar and the peptide aglycone structure (Ser/Thr). 27453399 3 30 theme Mucin-related 430:442 arg1 glycopeptides 444:456 Mucin-related glycopeptides 430:456 Mucin-related glycopeptides incorporating these motifs 430:483 Mucin-related glycopeptides incorporating these motifs were recognized by the monoclonal antibody (mAb) scFv-SM3, with activities depending on both the hydroxylation pattern (Glc/Gal/GlcNAc/GalNAc) of the sp(2)-iminosugar and the peptide aglycone structure (Ser/Thr). 27453399 2 31 theme stereoelectronic 338:353 arg1 bias 374:377 strong stereoelectronic and conformational bias 331:377 strong stereoelectronic and conformational bias imposed by the bicyclic sp(2)-iminosugar scaffold 331:427 The key synthetic step involves the completely diastereoselective α-glycosylation of Ser/Thr due to strong stereoelectronic and conformational bias imposed by the bicyclic sp(2)-iminosugar scaffold. 27453399 3 32 theme peptide 660:666 arg1 Ser/Thr 688:694 Ser/Thr 688:694 Ser/Thr 688:694 Mucin-related glycopeptides incorporating these motifs were recognized by the monoclonal antibody (mAb) scFv-SM3, with activities depending on both the hydroxylation pattern (Glc/Gal/GlcNAc/GalNAc) of the sp(2)-iminosugar and the peptide aglycone structure (Ser/Thr). 27453399 3 32 theme peptide 660:666 arg1 structure 677:685 the peptide aglycone structure 656:685 the peptide aglycone structure (Ser/Thr) 656:695 Mucin-related glycopeptides incorporating these motifs were recognized by the monoclonal antibody (mAb) scFv-SM3, with activities depending on both the hydroxylation pattern (Glc/Gal/GlcNAc/GalNAc) of the sp(2)-iminosugar and the peptide aglycone structure (Ser/Thr). 27453399 2 33 theme strong 331:336 arg1 bias 374:377 strong stereoelectronic and conformational bias 331:377 strong stereoelectronic and conformational bias imposed by the bicyclic sp(2)-iminosugar scaffold 331:427 The key synthetic step involves the completely diastereoselective α-glycosylation of Ser/Thr due to strong stereoelectronic and conformational bias imposed by the bicyclic sp(2)-iminosugar scaffold. 27453399 1 34 theme α-O-linked 183:192 arg1 linkage 209:215 an α-O-linked pseudoanomeric linkage 180:215 an α-O-linked pseudoanomeric linkage 180:215 The first examples of amino acid (Ser/Thr)-sp(2)-iminosugar glycomimetic conjugates featuring an α-O-linked pseudoanomeric linkage are reported. 25384478 0 0 theme 7942 99:102 arg1 transferase 37:47 The putative eukaryote-like O-GlcNAc transferase 0:47 The putative eukaryote-like O-GlcNAc transferase of the cyanobacterium Synechococcus elongatus PCC 7942 0:102 The putative eukaryote-like O-GlcNAc transferase of the cyanobacterium Synechococcus elongatus PCC 7942 hydrolyzes UDP-GlcNAc and is involved in multiple cellular processes. 25384478 2 1 theme eukaryotes 502:511 arg1 viability 484:492 the viability 480:492 the viability of many eukaryotes 480:511 The enzyme responsible for this modification, O-GlcNAc transferase (OGT), is conserved among a wide variety of organisms and is critical for the viability of many eukaryotes. 25384478 3 2 with OGTs 523:526 arg1 structures 540:549 domain structures 533:549 domain structures similar to those of eukaryotic OGTs 533:585 Although OGTs with domain structures similar to those of eukaryotic OGTs are predicted for many bacterial species, the cellular roles of these OGTs are unknown. 25384478 8 3 with OGTs 1241:1244 arg1 substitutions 1269:1281 single amino acid substitutions 1251:1281 single amino acid substitutions corresponding to mutations that reduce eukaryotic OGT activity 1251:1344 These phenotypes are rescued by reintroduction of the wild-type OGT but are not fully rescued by OGTs with single amino acid substitutions corresponding to mutations that reduce eukaryotic OGT activity. 25384478 2 4 theme many 497:500 arg1 eukaryotes 502:511 many eukaryotes 497:511 many eukaryotes 497:511 The enzyme responsible for this modification, O-GlcNAc transferase (OGT), is conserved among a wide variety of organisms and is critical for the viability of many eukaryotes. 25384478 1 5 theme posttranslational 178:194 arg1 addition 196:203 The posttranslational addition 174:203 The posttranslational addition of a single O-linked β-N-acetylglucosamine (O-GlcNAc) to serine or threonine residues 174:289 The posttranslational addition of a single O-linked β-N-acetylglucosamine (O-GlcNAc) to serine or threonine residues regulates numerous metazoan cellular processes. 25384478 3 6 theme OGTs 657:660 arg1 unknown 666:672 unknown 666:672 unknown 666:672 Although OGTs with domain structures similar to those of eukaryotic OGTs are predicted for many bacterial species, the cellular roles of these OGTs are unknown. 25384478 3 6 theme OGTs 657:660 arg1 roles 642:646 the cellular roles 629:646 the cellular roles of these OGTs 629:660 Although OGTs with domain structures similar to those of eukaryotic OGTs are predicted for many bacterial species, the cellular roles of these OGTs are unknown. 25384478 1 7 link O-linked 217:224 arg1 β-N-acetylglucosamine 226:246 a single O-linked β-N-acetylglucosamine 208:246 a single O-linked β-N-acetylglucosamine (O-GlcNAc) 208:257 The posttranslational addition of a single O-linked β-N-acetylglucosamine (O-GlcNAc) to serine or threonine residues regulates numerous metazoan cellular processes. 25384478 1 7 link O-linked 217:224 arg1 O-GlcNAc 249:256 O-GlcNAc 249:256 O-GlcNAc 249:256 The posttranslational addition of a single O-linked β-N-acetylglucosamine (O-GlcNAc) to serine or threonine residues regulates numerous metazoan cellular processes. 25384478 4 8 theme active-site 775:785 arg1 homology 787:794 active-site homology 775:794 active-site homology 775:794 We have identified a putative OGT in the cyanobacterium Synechococcus elongatus PCC 7942 that shows active-site homology and similar domain structure to eukaryotic OGTs. 25384478 9 9 theme mutant 1445:1450 arg1 OGTs 1452:1455 the mutant OGTs 1441:1455 the mutant OGTs that did not fully rescue the deletion mutant phenotypes 1441:1512 S. elongatus OGT purified from Escherichia coli hydrolyzed the sugar donor, UDP-GlcNAc, while the mutant OGTs that did not fully rescue the deletion mutant phenotypes had reduced or no activity. 25384478 7 10 contain have 1010:1013 arg2 higher 1015:1020 higher 1015:1020 higher 1015:1020 The mutant cells have higher free inorganic phosphate levels, wider thylakoid lumen, and differential accumulation of electron-dense inclusion bodies. 25384478 7 10 contain have 1010:1013 arg1 cells 1004:1008 The mutant cells 993:1008 The mutant cells 993:1008 The mutant cells have higher free inorganic phosphate levels, wider thylakoid lumen, and differential accumulation of electron-dense inclusion bodies. 25384478 7 10 contain have 1010:1013 arg2 lumen 1071:1075 wider thylakoid lumen 1055:1075 wider thylakoid lumen 1055:1075 The mutant cells have higher free inorganic phosphate levels, wider thylakoid lumen, and differential accumulation of electron-dense inclusion bodies. 25384478 7 10 contain have 1010:1013 arg2 accumulation 1095:1106 differential accumulation 1082:1106 differential accumulation of electron-dense inclusion bodies 1082:1141 The mutant cells have higher free inorganic phosphate levels, wider thylakoid lumen, and differential accumulation of electron-dense inclusion bodies. 25384478 7 11 theme bodies 1136:1141 arg1 accumulation 1095:1106 differential accumulation 1082:1106 differential accumulation of electron-dense inclusion bodies 1082:1141 The mutant cells have higher free inorganic phosphate levels, wider thylakoid lumen, and differential accumulation of electron-dense inclusion bodies. 25384478 1 12 theme numerous 301:308 arg1 processes 328:336 numerous metazoan cellular processes 301:336 numerous metazoan cellular processes 301:336 The posttranslational addition of a single O-linked β-N-acetylglucosamine (O-GlcNAc) to serine or threonine residues regulates numerous metazoan cellular processes. 25384478 8 13 theme wild-type 1198:1206 arg1 OGT 1208:1210 the wild-type OGT 1194:1210 the wild-type OGT 1194:1210 These phenotypes are rescued by reintroduction of the wild-type OGT but are not fully rescued by OGTs with single amino acid substitutions corresponding to mutations that reduce eukaryotic OGT activity. 25384478 4 14 theme elongatus 745:753 arg1 7942 759:762 the cyanobacterium Synechococcus elongatus PCC 7942 712:762 the cyanobacterium Synechococcus elongatus PCC 7942 712:762 We have identified a putative OGT in the cyanobacterium Synechococcus elongatus PCC 7942 that shows active-site homology and similar domain structure to eukaryotic OGTs. 25384478 5 15 theme deletion 852:859 arg1 mutant 861:866 An OGT deletion mutant 845:866 An OGT deletion mutant 845:866 An OGT deletion mutant was created and found to exhibit several phenotypes. 25384478 3 16 theme similar 551:557 arg1 structures 540:549 domain structures 533:549 domain structures similar to those of eukaryotic OGTs 533:585 Although OGTs with domain structures similar to those of eukaryotic OGTs are predicted for many bacterial species, the cellular roles of these OGTs are unknown. 25384478 7 17 dep higher 1015:1020 arg1 levels 1047:1052 free inorganic phosphate levels 1022:1052 free inorganic phosphate levels 1022:1052 The mutant cells have higher free inorganic phosphate levels, wider thylakoid lumen, and differential accumulation of electron-dense inclusion bodies. 25384478 8 18 theme single 1251:1256 arg1 substitutions 1269:1281 single amino acid substitutions 1251:1281 single amino acid substitutions corresponding to mutations that reduce eukaryotic OGT activity 1251:1344 These phenotypes are rescued by reintroduction of the wild-type OGT but are not fully rescued by OGTs with single amino acid substitutions corresponding to mutations that reduce eukaryotic OGT activity. 25384478 10 19 theme eukaryote-like 1579:1592 arg1 OGTs 1594:1597 bacterial eukaryote-like OGTs 1569:1597 bacterial eukaryote-like OGTs 1569:1597 These results suggest that bacterial eukaryote-like OGTs, like their eukaryotic counterparts, influence multiple processes. 25384478 9 20 theme S. 1347:1348 arg1 OGT 1360:1362 S. elongatus OGT 1347:1362 S. elongatus OGT purified from Escherichia coli 1347:1393 S. elongatus OGT purified from Escherichia coli hydrolyzed the sugar donor, UDP-GlcNAc, while the mutant OGTs that did not fully rescue the deletion mutant phenotypes had reduced or no activity. 25384478 7 21 theme electron-dense 1111:1124 arg1 bodies 1136:1141 electron-dense inclusion bodies 1111:1141 electron-dense inclusion bodies 1111:1141 The mutant cells have higher free inorganic phosphate levels, wider thylakoid lumen, and differential accumulation of electron-dense inclusion bodies. 25384478 8 22 theme OGT 1208:1210 arg1 reintroduction 1176:1189 reintroduction 1176:1189 reintroduction of the wild-type OGT 1176:1210 These phenotypes are rescued by reintroduction of the wild-type OGT but are not fully rescued by OGTs with single amino acid substitutions corresponding to mutations that reduce eukaryotic OGT activity. 25384478 0 23 theme putative 4:11 arg1 transferase 37:47 The putative eukaryote-like O-GlcNAc transferase 0:47 The putative eukaryote-like O-GlcNAc transferase of the cyanobacterium Synechococcus elongatus PCC 7942 0:102 The putative eukaryote-like O-GlcNAc transferase of the cyanobacterium Synechococcus elongatus PCC 7942 hydrolyzes UDP-GlcNAc and is involved in multiple cellular processes. 25384478 0 24 theme PCC 95:97 arg1 7942 99:102 the cyanobacterium Synechococcus elongatus PCC 7942 52:102 the cyanobacterium Synechococcus elongatus PCC 7942 52:102 The putative eukaryote-like O-GlcNAc transferase of the cyanobacterium Synechococcus elongatus PCC 7942 hydrolyzes UDP-GlcNAc and is involved in multiple cellular processes. 25384478 7 25 theme differential 1082:1093 arg1 accumulation 1095:1106 differential accumulation 1082:1106 differential accumulation of electron-dense inclusion bodies 1082:1141 The mutant cells have higher free inorganic phosphate levels, wider thylakoid lumen, and differential accumulation of electron-dense inclusion bodies. 25384478 10 26 theme bacterial 1569:1577 arg1 OGTs 1594:1597 bacterial eukaryote-like OGTs 1569:1597 bacterial eukaryote-like OGTs 1569:1597 These results suggest that bacterial eukaryote-like OGTs, like their eukaryotic counterparts, influence multiple processes. 25384478 4 27 theme PCC 755:757 arg1 7942 759:762 the cyanobacterium Synechococcus elongatus PCC 7942 712:762 the cyanobacterium Synechococcus elongatus PCC 7942 712:762 We have identified a putative OGT in the cyanobacterium Synechococcus elongatus PCC 7942 that shows active-site homology and similar domain structure to eukaryotic OGTs. 25384478 10 28 theme eukaryotic 1611:1620 arg1 counterparts 1622:1633 their eukaryotic counterparts 1605:1633 their eukaryotic counterparts 1605:1633 These results suggest that bacterial eukaryote-like OGTs, like their eukaryotic counterparts, influence multiple processes. 25384478 8 29 theme acid 1264:1267 arg1 substitutions 1269:1281 single amino acid substitutions 1251:1281 single amino acid substitutions corresponding to mutations that reduce eukaryotic OGT activity 1251:1344 These phenotypes are rescued by reintroduction of the wild-type OGT but are not fully rescued by OGTs with single amino acid substitutions corresponding to mutations that reduce eukaryotic OGT activity. 25384478 7 30 theme thylakoid 1061:1069 arg1 lumen 1071:1075 wider thylakoid lumen 1055:1075 wider thylakoid lumen 1055:1075 The mutant cells have higher free inorganic phosphate levels, wider thylakoid lumen, and differential accumulation of electron-dense inclusion bodies. 25384478 1 31 theme metazoan 310:317 arg1 processes 328:336 numerous metazoan cellular processes 301:336 numerous metazoan cellular processes 301:336 The posttranslational addition of a single O-linked β-N-acetylglucosamine (O-GlcNAc) to serine or threonine residues regulates numerous metazoan cellular processes. 25384478 2 32 theme responsible 350:360 arg1 enzyme 343:348 The enzyme 339:348 The enzyme responsible for this modification 339:382 The enzyme responsible for this modification, O-GlcNAc transferase (OGT), is conserved among a wide variety of organisms and is critical for the viability of many eukaryotes. 25384478 2 32 theme responsible 350:360 arg1 critical 467:474 critical 467:474 critical 467:474 The enzyme responsible for this modification, O-GlcNAc transferase (OGT), is conserved among a wide variety of organisms and is critical for the viability of many eukaryotes. 25384478 2 32 theme responsible 350:360 arg1 transferase 394:404 O-GlcNAc transferase 385:404 O-GlcNAc transferase (OGT) 385:410 The enzyme responsible for this modification, O-GlcNAc transferase (OGT), is conserved among a wide variety of organisms and is critical for the viability of many eukaryotes. 25384478 1 33 theme single 210:215 arg1 β-N-acetylglucosamine 226:246 a single O-linked β-N-acetylglucosamine 208:246 a single O-linked β-N-acetylglucosamine (O-GlcNAc) 208:257 The posttranslational addition of a single O-linked β-N-acetylglucosamine (O-GlcNAc) to serine or threonine residues regulates numerous metazoan cellular processes. 25384478 1 33 theme single 210:215 arg1 O-GlcNAc 249:256 O-GlcNAc 249:256 O-GlcNAc 249:256 The posttranslational addition of a single O-linked β-N-acetylglucosamine (O-GlcNAc) to serine or threonine residues regulates numerous metazoan cellular processes. 25384478 0 34 theme O-GlcNAc 28:35 arg1 transferase 37:47 The putative eukaryote-like O-GlcNAc transferase 0:47 The putative eukaryote-like O-GlcNAc transferase of the cyanobacterium Synechococcus elongatus PCC 7942 0:102 The putative eukaryote-like O-GlcNAc transferase of the cyanobacterium Synechococcus elongatus PCC 7942 hydrolyzes UDP-GlcNAc and is involved in multiple cellular processes. 25384478 1 35 theme cellular 319:326 arg1 processes 328:336 numerous metazoan cellular processes 301:336 numerous metazoan cellular processes 301:336 The posttranslational addition of a single O-linked β-N-acetylglucosamine (O-GlcNAc) to serine or threonine residues regulates numerous metazoan cellular processes. 25384478 3 36 theme eukaryotic 571:580 arg1 OGTs 582:585 eukaryotic OGTs 571:585 eukaryotic OGTs 571:585 Although OGTs with domain structures similar to those of eukaryotic OGTs are predicted for many bacterial species, the cellular roles of these OGTs are unknown. 25384478 3 37 theme bacterial 610:618 arg1 species 620:626 many bacterial species 605:626 many bacterial species 605:626 Although OGTs with domain structures similar to those of eukaryotic OGTs are predicted for many bacterial species, the cellular roles of these OGTs are unknown. 25384478 1 38 theme O-linked 217:224 arg1 β-N-acetylglucosamine 226:246 a single O-linked β-N-acetylglucosamine 208:246 a single O-linked β-N-acetylglucosamine (O-GlcNAc) 208:257 The posttranslational addition of a single O-linked β-N-acetylglucosamine (O-GlcNAc) to serine or threonine residues regulates numerous metazoan cellular processes. 25384478 1 38 theme O-linked 217:224 arg1 O-GlcNAc 249:256 O-GlcNAc 249:256 O-GlcNAc 249:256 The posttranslational addition of a single O-linked β-N-acetylglucosamine (O-GlcNAc) to serine or threonine residues regulates numerous metazoan cellular processes. 25384478 2 39 theme organisms 450:458 arg1 organisms 450:458 organisms 450:458 organisms 450:458 The enzyme responsible for this modification, O-GlcNAc transferase (OGT), is conserved among a wide variety of organisms and is critical for the viability of many eukaryotes. 25384478 2 39 theme organisms 450:458 arg1 variety 439:445 a wide variety 432:445 a wide variety of organisms 432:458 The enzyme responsible for this modification, O-GlcNAc transferase (OGT), is conserved among a wide variety of organisms and is critical for the viability of many eukaryotes. 25384478 1 40 dep serine 262:267 arg1 residues 282:289 residues 282:289 residues 282:289 The posttranslational addition of a single O-linked β-N-acetylglucosamine (O-GlcNAc) to serine or threonine residues regulates numerous metazoan cellular processes. 25384478 4 41 theme putative 696:703 arg1 OGT 705:707 a putative OGT 694:707 a putative OGT in the cyanobacterium Synechococcus elongatus PCC 7942 that shows active-site homology and similar domain structure to eukaryotic OGTs 694:842 We have identified a putative OGT in the cyanobacterium Synechococcus elongatus PCC 7942 that shows active-site homology and similar domain structure to eukaryotic OGTs. 25384478 1 42 theme β-N-acetylglucosamine 226:246 arg1 addition 196:203 The posttranslational addition 174:203 The posttranslational addition of a single O-linked β-N-acetylglucosamine (O-GlcNAc) to serine or threonine residues 174:289 The posttranslational addition of a single O-linked β-N-acetylglucosamine (O-GlcNAc) to serine or threonine residues regulates numerous metazoan cellular processes. 25384478 0 43 theme cellular 154:161 arg1 processes 163:171 multiple cellular processes 145:171 multiple cellular processes 145:171 The putative eukaryote-like O-GlcNAc transferase of the cyanobacterium Synechococcus elongatus PCC 7942 hydrolyzes UDP-GlcNAc and is involved in multiple cellular processes. 25384478 9 44 theme deletion 1487:1494 arg1 phenotypes 1503:1512 the deletion mutant phenotypes 1483:1512 the deletion mutant phenotypes 1483:1512 S. elongatus OGT purified from Escherichia coli hydrolyzed the sugar donor, UDP-GlcNAc, while the mutant OGTs that did not fully rescue the deletion mutant phenotypes had reduced or no activity. 25384478 0 45 dep cyanobacterium 56:69 arg1 Synechococcus 71:83 Synechococcus 71:83 Synechococcus 71:83 The putative eukaryote-like O-GlcNAc transferase of the cyanobacterium Synechococcus elongatus PCC 7942 hydrolyzes UDP-GlcNAc and is involved in multiple cellular processes. 25384478 8 46 theme amino 1258:1262 arg1 substitutions 1269:1281 single amino acid substitutions 1251:1281 single amino acid substitutions corresponding to mutations that reduce eukaryotic OGT activity 1251:1344 These phenotypes are rescued by reintroduction of the wild-type OGT but are not fully rescued by OGTs with single amino acid substitutions corresponding to mutations that reduce eukaryotic OGT activity. 25384478 2 47 theme wide 434:437 arg1 organisms 450:458 organisms 450:458 organisms 450:458 The enzyme responsible for this modification, O-GlcNAc transferase (OGT), is conserved among a wide variety of organisms and is critical for the viability of many eukaryotes. 25384478 2 47 theme wide 434:437 arg1 variety 439:445 a wide variety 432:445 a wide variety of organisms 432:458 The enzyme responsible for this modification, O-GlcNAc transferase (OGT), is conserved among a wide variety of organisms and is critical for the viability of many eukaryotes. 25384478 9 48 dep S. 1347:1348 arg1 elongatus 1350:1358 elongatus 1350:1358 elongatus 1350:1358 S. elongatus OGT purified from Escherichia coli hydrolyzed the sugar donor, UDP-GlcNAc, while the mutant OGTs that did not fully rescue the deletion mutant phenotypes had reduced or no activity. 25384478 0 49 theme multiple 145:152 arg1 processes 163:171 multiple cellular processes 145:171 multiple cellular processes 145:171 The putative eukaryote-like O-GlcNAc transferase of the cyanobacterium Synechococcus elongatus PCC 7942 hydrolyzes UDP-GlcNAc and is involved in multiple cellular processes. 25384478 4 50 theme eukaryotic 828:837 arg1 OGTs 839:842 eukaryotic OGTs 828:842 eukaryotic OGTs 828:842 We have identified a putative OGT in the cyanobacterium Synechococcus elongatus PCC 7942 that shows active-site homology and similar domain structure to eukaryotic OGTs. 25384478 7 51 theme free 1022:1025 arg1 levels 1047:1052 free inorganic phosphate levels 1022:1052 free inorganic phosphate levels 1022:1052 The mutant cells have higher free inorganic phosphate levels, wider thylakoid lumen, and differential accumulation of electron-dense inclusion bodies. 25384478 8 52 theme eukaryotic 1322:1331 arg1 activity 1337:1344 eukaryotic OGT activity 1322:1344 eukaryotic OGT activity 1322:1344 These phenotypes are rescued by reintroduction of the wild-type OGT but are not fully rescued by OGTs with single amino acid substitutions corresponding to mutations that reduce eukaryotic OGT activity. 25384478 0 53 theme cyanobacterium 56:69 arg1 7942 99:102 the cyanobacterium Synechococcus elongatus PCC 7942 52:102 the cyanobacterium Synechococcus elongatus PCC 7942 52:102 The putative eukaryote-like O-GlcNAc transferase of the cyanobacterium Synechococcus elongatus PCC 7942 hydrolyzes UDP-GlcNAc and is involved in multiple cellular processes. 25384478 7 54 theme inorganic 1027:1035 arg1 levels 1047:1052 free inorganic phosphate levels 1022:1052 free inorganic phosphate levels 1022:1052 The mutant cells have higher free inorganic phosphate levels, wider thylakoid lumen, and differential accumulation of electron-dense inclusion bodies. 25384478 2 55 theme O-GlcNAc 385:392 arg1 enzyme 343:348 The enzyme 339:348 The enzyme responsible for this modification 339:382 The enzyme responsible for this modification, O-GlcNAc transferase (OGT), is conserved among a wide variety of organisms and is critical for the viability of many eukaryotes. 25384478 2 55 theme O-GlcNAc 385:392 arg1 OGT 407:409 OGT 407:409 OGT 407:409 The enzyme responsible for this modification, O-GlcNAc transferase (OGT), is conserved among a wide variety of organisms and is critical for the viability of many eukaryotes. 25384478 2 55 theme O-GlcNAc 385:392 arg1 transferase 394:404 O-GlcNAc transferase 385:404 O-GlcNAc transferase (OGT) 385:410 The enzyme responsible for this modification, O-GlcNAc transferase (OGT), is conserved among a wide variety of organisms and is critical for the viability of many eukaryotes. 25384478 9 56 contain had 1514:1516 arg2 activity 1532:1539 no activity 1529:1539 no activity 1529:1539 S. elongatus OGT purified from Escherichia coli hydrolyzed the sugar donor, UDP-GlcNAc, while the mutant OGTs that did not fully rescue the deletion mutant phenotypes had reduced or no activity. 25384478 9 56 contain had 1514:1516 arg2 reduced 1518:1524 reduced 1518:1524 reduced 1518:1524 S. elongatus OGT purified from Escherichia coli hydrolyzed the sugar donor, UDP-GlcNAc, while the mutant OGTs that did not fully rescue the deletion mutant phenotypes had reduced or no activity. 25384478 9 56 contain had 1514:1516 arg1 OGTs 1452:1455 the mutant OGTs 1441:1455 the mutant OGTs that did not fully rescue the deletion mutant phenotypes 1441:1512 S. elongatus OGT purified from Escherichia coli hydrolyzed the sugar donor, UDP-GlcNAc, while the mutant OGTs that did not fully rescue the deletion mutant phenotypes had reduced or no activity. 25384478 7 57 theme wider 1055:1059 arg1 lumen 1071:1075 wider thylakoid lumen 1055:1075 wider thylakoid lumen 1055:1075 The mutant cells have higher free inorganic phosphate levels, wider thylakoid lumen, and differential accumulation of electron-dense inclusion bodies. 25384478 3 58 theme many 605:608 arg1 species 620:626 many bacterial species 605:626 many bacterial species 605:626 Although OGTs with domain structures similar to those of eukaryotic OGTs are predicted for many bacterial species, the cellular roles of these OGTs are unknown. 25384478 7 59 theme inclusion 1126:1134 arg1 bodies 1136:1141 electron-dense inclusion bodies 1111:1141 electron-dense inclusion bodies 1111:1141 The mutant cells have higher free inorganic phosphate levels, wider thylakoid lumen, and differential accumulation of electron-dense inclusion bodies. 25384478 9 60 theme sugar 1410:1414 arg1 UDP-GlcNAc 1423:1432 UDP-GlcNAc 1423:1432 UDP-GlcNAc 1423:1432 S. elongatus OGT purified from Escherichia coli hydrolyzed the sugar donor, UDP-GlcNAc, while the mutant OGTs that did not fully rescue the deletion mutant phenotypes had reduced or no activity. 25384478 9 60 theme sugar 1410:1414 arg1 donor 1416:1420 the sugar donor 1406:1420 the sugar donor 1406:1420 S. elongatus OGT purified from Escherichia coli hydrolyzed the sugar donor, UDP-GlcNAc, while the mutant OGTs that did not fully rescue the deletion mutant phenotypes had reduced or no activity. 25384478 7 61 theme phosphate 1037:1045 arg1 levels 1047:1052 free inorganic phosphate levels 1022:1052 free inorganic phosphate levels 1022:1052 The mutant cells have higher free inorganic phosphate levels, wider thylakoid lumen, and differential accumulation of electron-dense inclusion bodies. 25384478 4 62 theme domain 808:813 arg1 structure 815:823 similar domain structure 800:823 similar domain structure 800:823 We have identified a putative OGT in the cyanobacterium Synechococcus elongatus PCC 7942 that shows active-site homology and similar domain structure to eukaryotic OGTs. 25384478 3 63 theme cellular 633:640 arg1 unknown 666:672 unknown 666:672 unknown 666:672 Although OGTs with domain structures similar to those of eukaryotic OGTs are predicted for many bacterial species, the cellular roles of these OGTs are unknown. 25384478 3 63 theme cellular 633:640 arg1 roles 642:646 the cellular roles 629:646 the cellular roles of these OGTs 629:660 Although OGTs with domain structures similar to those of eukaryotic OGTs are predicted for many bacterial species, the cellular roles of these OGTs are unknown. 25384478 8 64 theme OGT 1333:1335 arg1 activity 1337:1344 eukaryotic OGT activity 1322:1344 eukaryotic OGT activity 1322:1344 These phenotypes are rescued by reintroduction of the wild-type OGT but are not fully rescued by OGTs with single amino acid substitutions corresponding to mutations that reduce eukaryotic OGT activity. 25384478 4 65 theme similar 800:806 arg1 structure 815:823 similar domain structure 800:823 similar domain structure 800:823 We have identified a putative OGT in the cyanobacterium Synechococcus elongatus PCC 7942 that shows active-site homology and similar domain structure to eukaryotic OGTs. 25384478 7 66 theme mutant 997:1002 arg1 cells 1004:1008 The mutant cells 993:1008 The mutant cells 993:1008 The mutant cells have higher free inorganic phosphate levels, wider thylakoid lumen, and differential accumulation of electron-dense inclusion bodies. 25384478 4 67 theme cyanobacterium 716:729 arg1 7942 759:762 the cyanobacterium Synechococcus elongatus PCC 7942 712:762 the cyanobacterium Synechococcus elongatus PCC 7942 712:762 We have identified a putative OGT in the cyanobacterium Synechococcus elongatus PCC 7942 that shows active-site homology and similar domain structure to eukaryotic OGTs. 25384478 4 68 dep cyanobacterium 716:729 arg1 Synechococcus 731:743 Synechococcus 731:743 Synechococcus 731:743 We have identified a putative OGT in the cyanobacterium Synechococcus elongatus PCC 7942 that shows active-site homology and similar domain structure to eukaryotic OGTs. 25384478 0 69 theme elongatus 85:93 arg1 7942 99:102 the cyanobacterium Synechococcus elongatus PCC 7942 52:102 the cyanobacterium Synechococcus elongatus PCC 7942 52:102 The putative eukaryote-like O-GlcNAc transferase of the cyanobacterium Synechococcus elongatus PCC 7942 hydrolyzes UDP-GlcNAc and is involved in multiple cellular processes. 25384478 9 70 theme mutant 1496:1501 arg1 phenotypes 1503:1512 the deletion mutant phenotypes 1483:1512 the deletion mutant phenotypes 1483:1512 S. elongatus OGT purified from Escherichia coli hydrolyzed the sugar donor, UDP-GlcNAc, while the mutant OGTs that did not fully rescue the deletion mutant phenotypes had reduced or no activity. 25384478 5 71 theme OGT 848:850 arg1 mutant 861:866 An OGT deletion mutant 845:866 An OGT deletion mutant 845:866 An OGT deletion mutant was created and found to exhibit several phenotypes. 25384478 3 72 theme domain 533:538 arg1 structures 540:549 domain structures 533:549 domain structures similar to those of eukaryotic OGTs 533:585 Although OGTs with domain structures similar to those of eukaryotic OGTs are predicted for many bacterial species, the cellular roles of these OGTs are unknown. 25384478 10 73 theme multiple 1646:1653 arg1 processes 1655:1663 multiple processes 1646:1663 multiple processes 1646:1663 These results suggest that bacterial eukaryote-like OGTs, like their eukaryotic counterparts, influence multiple processes. 25384478 6 74 theme mutant 940:945 arg1 cells 947:951 mutant cells 940:951 mutant cells 940:951 Without agitation, mutant cells aggregate and settle out of the medium. 25384478 0 75 theme eukaryote-like 13:26 arg1 transferase 37:47 The putative eukaryote-like O-GlcNAc transferase 0:47 The putative eukaryote-like O-GlcNAc transferase of the cyanobacterium Synechococcus elongatus PCC 7942 0:102 The putative eukaryote-like O-GlcNAc transferase of the cyanobacterium Synechococcus elongatus PCC 7942 hydrolyzes UDP-GlcNAc and is involved in multiple cellular processes. 25384478 5 76 theme several 901:907 arg1 phenotypes 909:918 several phenotypes 901:918 several phenotypes 901:918 An OGT deletion mutant was created and found to exhibit several phenotypes. 25384478 4 77 from OGT 705:707 arg1 7942 759:762 the cyanobacterium Synechococcus elongatus PCC 7942 712:762 the cyanobacterium Synechococcus elongatus PCC 7942 712:762 We have identified a putative OGT in the cyanobacterium Synechococcus elongatus PCC 7942 that shows active-site homology and similar domain structure to eukaryotic OGTs. 24304661 8 0 theme TET3 1001:1004 arg1 OGT 970:972 OGT 970:972 OGT 970:972 First, we conducted mass spectrometric analysis in combination with affinity purification of FLAG-TET3, which identified OGT as an important partner of TET3. 24304661 8 0 theme TET3 1001:1004 arg1 partner 990:996 an important partner 977:996 an important partner of TET3 977:1004 First, we conducted mass spectrometric analysis in combination with affinity purification of FLAG-TET3, which identified OGT as an important partner of TET3. 24304661 2 1 theme translocation 329:341 arg1 family 349:354 the ten-eleven translocation (TET) family 314:354 the ten-eleven translocation (TET) family 314:354 Recently, it was reported that 5-methylcytosine (5mC) is converted to 5-hydroxymethylcytosine (5hmC) by proteins in the ten-eleven translocation (TET) family. 24304661 2 2 from proteins 302:309 arg1 family 349:354 the ten-eleven translocation (TET) family 314:354 the ten-eleven translocation (TET) family 314:354 Recently, it was reported that 5-methylcytosine (5mC) is converted to 5-hydroxymethylcytosine (5hmC) by proteins in the ten-eleven translocation (TET) family. 24304661 0 3 from presence 53:60 arg1 chromatin 72:80 chromatin 72:80 chromatin 72:80 TET3-OGT interaction increases the stability and the presence of OGT in chromatin. 24304661 9 4 theme deletion 1055:1062 arg1 mutants 1064:1070 deletion mutants 1055:1070 deletion mutants 1055:1070 Co-immunoprecipitation assays using a series of deletion mutants showed that the C-terminal H domain of TET3 was required for its interaction with OGT. 24304661 9 5 theme C-terminal 1088:1097 arg1 TET3 1111:1114 TET3 1111:1114 TET3 1111:1114 Co-immunoprecipitation assays using a series of deletion mutants showed that the C-terminal H domain of TET3 was required for its interaction with OGT. 24304661 9 5 theme C-terminal 1088:1097 arg1 domain 1101:1106 the C-terminal H domain 1084:1106 the C-terminal H domain of TET3 1084:1114 Co-immunoprecipitation assays using a series of deletion mutants showed that the C-terminal H domain of TET3 was required for its interaction with OGT. 24304661 5 6 theme O-GlcNAc 610:617 arg1 OGT 632:634 OGT 632:634 OGT 632:634 In addition, modification with O-linked-N-acetylglucosamine (O-GlcNAc) by O-GlcNAc transferase (OGT) was recently identified as a novel histone modification. 24304661 5 6 theme O-GlcNAc 610:617 arg1 transferase 619:629 O-GlcNAc transferase 610:629 O-GlcNAc transferase (OGT) 610:635 In addition, modification with O-linked-N-acetylglucosamine (O-GlcNAc) by O-GlcNAc transferase (OGT) was recently identified as a novel histone modification. 24304661 7 7 theme biochemical 825:835 arg1 approaches 837:846 biochemical approaches 825:846 biochemical approaches 825:846 We attempted to elucidate the mechanism of its regulation by biochemical approaches. 24304661 1 8 theme DNA 156:158 arg1 methylation 160:170 DNA methylation 156:170 DNA methylation 156:170 Gene expression is controlled by alterations in the epigenome, including DNA methylation and histone modification. 24304661 1 9 from alterations 116:126 arg1 epigenome 135:143 the epigenome 131:143 the epigenome 131:143 Gene expression is controlled by alterations in the epigenome, including DNA methylation and histone modification. 24304661 8 10 with combination 900:910 arg1 purification 926:937 affinity purification 917:937 affinity purification 917:937 First, we conducted mass spectrometric analysis in combination with affinity purification of FLAG-TET3, which identified OGT as an important partner of TET3. 24304661 9 11 theme mutants 1064:1070 arg1 series 1045:1050 a series 1043:1050 a series of deletion mutants 1043:1070 Co-immunoprecipitation assays using a series of deletion mutants showed that the C-terminal H domain of TET3 was required for its interaction with OGT. 24304661 3 12 theme mechanism 403:411 arg1 part 391:394 part 391:394 part of the mechanism by which methylated DNA is demethylated 391:451 This conversion is believed to be part of the mechanism by which methylated DNA is demethylated. 24304661 0 13 from stability 35:43 arg1 chromatin 72:80 chromatin 72:80 chromatin 72:80 TET3-OGT interaction increases the stability and the presence of OGT in chromatin. 24304661 11 14 theme protein 1412:1418 arg1 stabilization 1391:1403 the stabilization 1387:1403 the stabilization of OGT protein 1387:1418 Moreover, we showed that TET3 enhanced its localization to chromatin through the stabilization of OGT protein. 24304661 7 15 theme regulation 811:820 arg1 mechanism 794:802 the mechanism 790:802 the mechanism of its regulation by biochemical approaches 790:846 We attempted to elucidate the mechanism of its regulation by biochemical approaches. 24304661 0 16 theme TET3-OGT 0:7 arg1 interaction 9:19 TET3-OGT interaction 0:19 TET3-OGT interaction 0:19 TET3-OGT interaction increases the stability and the presence of OGT in chromatin. 24304661 1 17 theme Gene 83:86 arg1 expression 88:97 Gene expression 83:97 Gene expression 83:97 Gene expression is controlled by alterations in the epigenome, including DNA methylation and histone modification. 24304661 1 18 theme histone 176:182 arg1 modification 184:195 histone modification 176:195 histone modification 176:195 Gene expression is controlled by alterations in the epigenome, including DNA methylation and histone modification. 24304661 0 19 attach presence 53:60 arg1 chromatin 72:80 chromatin 72:80 chromatin 72:80 TET3-OGT interaction increases the stability and the presence of OGT in chromatin. 24304661 0 19 attach presence 53:60 arg2 OGT 65:67 OGT 65:67 OGT 65:67 TET3-OGT interaction increases the stability and the presence of OGT in chromatin. 24304661 10 20 theme global 1262:1267 arg1 hydroxylation 1269:1281 the global hydroxylation 1258:1281 the global hydroxylation of methylcytosine by TET3 1258:1307 Furthermore, we showed that TET3 is GlcNAcylated by OGT, although the GlcNAcylation did not affect the global hydroxylation of methylcytosine by TET3. 24304661 3 21 theme methylated 422:431 arg1 DNA 433:435 methylated DNA 422:435 methylated DNA 422:435 This conversion is believed to be part of the mechanism by which methylated DNA is demethylated. 24304661 9 22 theme H 1099:1099 arg1 TET3 1111:1114 TET3 1111:1114 TET3 1111:1114 Co-immunoprecipitation assays using a series of deletion mutants showed that the C-terminal H domain of TET3 was required for its interaction with OGT. 24304661 9 22 theme H 1099:1099 arg1 domain 1101:1106 the C-terminal H domain 1084:1106 the C-terminal H domain of TET3 1084:1114 Co-immunoprecipitation assays using a series of deletion mutants showed that the C-terminal H domain of TET3 was required for its interaction with OGT. 24304661 8 23 theme spectrometric 874:886 arg1 analysis 888:895 mass spectrometric analysis 869:895 mass spectrometric analysis 869:895 First, we conducted mass spectrometric analysis in combination with affinity purification of FLAG-TET3, which identified OGT as an important partner of TET3. 24304661 5 24 with modification 549:560 arg1 O-GlcNAc 597:604 O-GlcNAc 597:604 O-GlcNAc 597:604 In addition, modification with O-linked-N-acetylglucosamine (O-GlcNAc) by O-GlcNAc transferase (OGT) was recently identified as a novel histone modification. 24304661 5 24 with modification 549:560 arg1 O-linked-N-acetylglucosamine 567:594 O-linked-N-acetylglucosamine 567:594 O-linked-N-acetylglucosamine (O-GlcNAc) 567:605 In addition, modification with O-linked-N-acetylglucosamine (O-GlcNAc) by O-GlcNAc transferase (OGT) was recently identified as a novel histone modification. 24304661 12 25 theme novel 1449:1453 arg1 function 1455:1462 a novel function 1447:1462 a novel function of TET3 that likely supports the function of OGT 1447:1511 Taken together, we showed a novel function of TET3 that likely supports the function of OGT. 24304661 8 26 theme mass 869:872 arg1 analysis 888:895 mass spectrometric analysis 869:895 mass spectrometric analysis 869:895 First, we conducted mass spectrometric analysis in combination with affinity purification of FLAG-TET3, which identified OGT as an important partner of TET3. 24304661 11 27 theme OGT 1408:1410 arg1 protein 1412:1418 OGT protein 1408:1418 OGT protein 1408:1418 Moreover, we showed that TET3 enhanced its localization to chromatin through the stabilization of OGT protein. 24304661 12 28 theme TET3 1467:1470 arg1 function 1455:1462 a novel function 1447:1462 a novel function of TET3 that likely supports the function of OGT 1447:1511 Taken together, we showed a novel function of TET3 that likely supports the function of OGT. 24304661 2 29 theme ten-eleven 318:327 arg1 family 349:354 the ten-eleven translocation (TET) family 314:354 the ten-eleven translocation (TET) family 314:354 Recently, it was reported that 5-methylcytosine (5mC) is converted to 5-hydroxymethylcytosine (5hmC) by proteins in the ten-eleven translocation (TET) family. 24304661 9 30 theme TET3 1111:1114 arg1 TET3 1111:1114 TET3 1111:1114 TET3 1111:1114 Co-immunoprecipitation assays using a series of deletion mutants showed that the C-terminal H domain of TET3 was required for its interaction with OGT. 24304661 9 30 theme TET3 1111:1114 arg1 domain 1101:1106 the C-terminal H domain 1084:1106 the C-terminal H domain of TET3 1084:1114 Co-immunoprecipitation assays using a series of deletion mutants showed that the C-terminal H domain of TET3 was required for its interaction with OGT. 24304661 8 31 theme important 980:988 arg1 OGT 970:972 OGT 970:972 OGT 970:972 First, we conducted mass spectrometric analysis in combination with affinity purification of FLAG-TET3, which identified OGT as an important partner of TET3. 24304661 8 31 theme important 980:988 arg1 partner 990:996 an important partner 977:996 an important partner of TET3 977:1004 First, we conducted mass spectrometric analysis in combination with affinity purification of FLAG-TET3, which identified OGT as an important partner of TET3. 24304661 5 32 theme novel 666:670 arg1 modification 549:560 modification 549:560 modification with O-linked-N-acetylglucosamine (O-GlcNAc) by O-GlcNAc transferase (OGT) 549:635 In addition, modification with O-linked-N-acetylglucosamine (O-GlcNAc) by O-GlcNAc transferase (OGT) was recently identified as a novel histone modification. 24304661 5 32 theme novel 666:670 arg1 modification 680:691 a novel histone modification 664:691 a novel histone modification 664:691 In addition, modification with O-linked-N-acetylglucosamine (O-GlcNAc) by O-GlcNAc transferase (OGT) was recently identified as a novel histone modification. 24304661 10 33 theme methylcytosine 1286:1299 arg1 hydroxylation 1269:1281 the global hydroxylation 1258:1281 the global hydroxylation of methylcytosine by TET3 1258:1307 Furthermore, we showed that TET3 is GlcNAcylated by OGT, although the GlcNAcylation did not affect the global hydroxylation of methylcytosine by TET3. 24304661 5 34 theme histone 672:678 arg1 modification 549:560 modification 549:560 modification with O-linked-N-acetylglucosamine (O-GlcNAc) by O-GlcNAc transferase (OGT) 549:635 In addition, modification with O-linked-N-acetylglucosamine (O-GlcNAc) by O-GlcNAc transferase (OGT) was recently identified as a novel histone modification. 24304661 5 34 theme histone 672:678 arg1 modification 680:691 a novel histone modification 664:691 a novel histone modification 664:691 In addition, modification with O-linked-N-acetylglucosamine (O-GlcNAc) by O-GlcNAc transferase (OGT) was recently identified as a novel histone modification. 24304661 6 35 theme TET3 716:719 arg1 unclear 755:761 unclear 755:761 unclear 755:761 Herein, we focused on TET3, the regulation of which is still unclear. 24304661 6 35 theme TET3 716:719 arg1 regulation 726:735 the regulation 722:735 the regulation 722:735 Herein, we focused on TET3, the regulation of which is still unclear. 24304661 9 36 with interaction 1137:1147 arg1 OGT 1154:1156 OGT 1154:1156 OGT 1154:1156 Co-immunoprecipitation assays using a series of deletion mutants showed that the C-terminal H domain of TET3 was required for its interaction with OGT. 24304661 0 37 theme OGT 65:67 arg1 stability 35:43 the stability 31:43 the stability 31:43 TET3-OGT interaction increases the stability and the presence of OGT in chromatin. 24304661 0 37 theme OGT 65:67 arg1 presence 53:60 the presence 49:60 the presence of OGT in chromatin 49:80 TET3-OGT interaction increases the stability and the presence of OGT in chromatin. 24304661 8 38 theme affinity 917:924 arg1 purification 926:937 affinity purification 917:937 affinity purification 917:937 First, we conducted mass spectrometric analysis in combination with affinity purification of FLAG-TET3, which identified OGT as an important partner of TET3. 24304661 9 39 theme Co-immunoprecipitation 1007:1028 arg1 assays 1030:1035 Co-immunoprecipitation assays 1007:1035 Co-immunoprecipitation assays using a series of deletion mutants 1007:1070 Co-immunoprecipitation assays using a series of deletion mutants showed that the C-terminal H domain of TET3 was required for its interaction with OGT. 24304661 8 40 theme FLAG-TET3 942:950 arg1 purification 926:937 affinity purification 917:937 affinity purification 917:937 First, we conducted mass spectrometric analysis in combination with affinity purification of FLAG-TET3, which identified OGT as an important partner of TET3. 24304661 2 41 theme TET 344:346 arg1 family 349:354 the ten-eleven translocation (TET) family 314:354 the ten-eleven translocation (TET) family 314:354 Recently, it was reported that 5-methylcytosine (5mC) is converted to 5-hydroxymethylcytosine (5hmC) by proteins in the ten-eleven translocation (TET) family. 24304661 12 42 theme OGT 1509:1511 arg1 function 1497:1504 the function 1493:1504 the function of OGT 1493:1511 Taken together, we showed a novel function of TET3 that likely supports the function of OGT. 27126545 5 0 theme AD 666:667 arg1 brain 669:673 AD brain 666:673 AD brain 666:673 The O-GlcNAcylation levels of brain proteins including tau are decreased in AD brain, probably due to decreased brain glucose metabolism. 27126545 7 1 theme neurodegenerative 1080:1096 arg1 diseases 1098:1105 other neurodegenerative diseases 1074:1105 other neurodegenerative diseases 1074:1105 Studies on mouse models of tauopathies suggest a neuroprotective role of pharmacological elevation of brain O-GlcNAc, which could potentially be a promising approach for treating AD and other neurodegenerative diseases. 27126545 2 2 from discovery 199:207 arg1 phosphorylation 263:277 tau phosphorylation 259:277 tau phosphorylation 259:277 The discovery of O-GlcNAc modification of tau and its impact on tau phosphorylation has attracted recent research interest in O-GlcNAc studies in the Alzheimer's disease (AD) field. 27126545 5 3 theme brain 620:624 arg1 tau 645:647 tau 645:647 tau 645:647 The O-GlcNAcylation levels of brain proteins including tau are decreased in AD brain, probably due to decreased brain glucose metabolism. 27126545 5 3 theme brain 620:624 arg1 proteins 626:633 brain proteins 620:633 brain proteins including tau 620:647 The O-GlcNAcylation levels of brain proteins including tau are decreased in AD brain, probably due to decreased brain glucose metabolism. 27126545 7 4 theme tauopathies 915:925 arg1 models 905:910 mouse models 899:910 mouse models of tauopathies 899:925 Studies on mouse models of tauopathies suggest a neuroprotective role of pharmacological elevation of brain O-GlcNAc, which could potentially be a promising approach for treating AD and other neurodegenerative diseases. 27126545 7 5 theme promising 1035:1043 arg1 role 953:956 a neuroprotective role 935:956 a neuroprotective role 935:956 Studies on mouse models of tauopathies suggest a neuroprotective role of pharmacological elevation of brain O-GlcNAc, which could potentially be a promising approach for treating AD and other neurodegenerative diseases. 27126545 7 5 theme promising 1035:1043 arg1 approach 1045:1052 a promising approach 1033:1052 a promising approach for treating AD and other neurodegenerative diseases 1033:1105 Studies on mouse models of tauopathies suggest a neuroprotective role of pharmacological elevation of brain O-GlcNAc, which could potentially be a promising approach for treating AD and other neurodegenerative diseases. 27126545 4 6 theme enzymes 485:491 arg1 activities 467:476 activities 467:476 activities 467:476 The expressions and activities of the enzymes catalyzing O-GlcNAc cycling are several-fold higher in the brain than in the peripheral tissues. 27126545 4 6 theme enzymes 485:491 arg1 expressions 451:461 expressions 451:461 expressions 451:461 The expressions and activities of the enzymes catalyzing O-GlcNAc cycling are several-fold higher in the brain than in the peripheral tissues. 27126545 5 7 theme proteins 626:633 arg1 levels 610:615 The O-GlcNAcylation levels 590:615 The O-GlcNAcylation levels of brain proteins including tau 590:647 The O-GlcNAcylation levels of brain proteins including tau are decreased in AD brain, probably due to decreased brain glucose metabolism. 27126545 7 8 theme mouse 899:903 arg1 models 905:910 mouse models 899:910 mouse models of tauopathies 899:925 Studies on mouse models of tauopathies suggest a neuroprotective role of pharmacological elevation of brain O-GlcNAc, which could potentially be a promising approach for treating AD and other neurodegenerative diseases. 27126545 4 9 dep expressions 451:461 arg1 The 447:449 The 447:449 The 447:449 The expressions and activities of the enzymes catalyzing O-GlcNAc cycling are several-fold higher in the brain than in the peripheral tissues. 27126545 2 10 from tau 237:239 arg1 phosphorylation 263:277 tau phosphorylation 259:277 tau phosphorylation 259:277 The discovery of O-GlcNAc modification of tau and its impact on tau phosphorylation has attracted recent research interest in O-GlcNAc studies in the Alzheimer's disease (AD) field. 27126545 6 11 theme decreased 819:827 arg1 metabolism 843:852 decreased brain glucose metabolism 819:852 decreased brain glucose metabolism 819:852 The reduction of brain O-GlcNAcylation appears to mediate the molecular mechanism by which decreased brain glucose metabolism contributes to neurodegeneration. 27126545 2 12 theme research 300:307 arg1 interest 309:316 recent research interest 293:316 recent research interest 293:316 The discovery of O-GlcNAc modification of tau and its impact on tau phosphorylation has attracted recent research interest in O-GlcNAc studies in the Alzheimer's disease (AD) field. 27126545 4 13 theme O-GlcNAc 504:511 arg1 cycling 513:519 O-GlcNAc cycling 504:519 O-GlcNAc cycling 504:519 The expressions and activities of the enzymes catalyzing O-GlcNAc cycling are several-fold higher in the brain than in the peripheral tissues. 27126545 7 14 theme brain 990:994 arg1 O-GlcNAc 996:1003 brain O-GlcNAc 990:1003 brain O-GlcNAc 990:1003 Studies on mouse models of tauopathies suggest a neuroprotective role of pharmacological elevation of brain O-GlcNAc, which could potentially be a promising approach for treating AD and other neurodegenerative diseases. 27126545 2 15 theme recent 293:298 arg1 interest 309:316 recent research interest 293:316 recent research interest 293:316 The discovery of O-GlcNAc modification of tau and its impact on tau phosphorylation has attracted recent research interest in O-GlcNAc studies in the Alzheimer's disease (AD) field. 27126545 3 16 theme proteins 393:400 arg1 Modification 377:388 Modification 377:388 Modification of proteins by O-GlcNAc 377:412 Modification of proteins by O-GlcNAc occurs extensively in the brain. 27126545 4 17 theme peripheral 570:579 arg1 tissues 581:587 the peripheral tissues 566:587 the peripheral tissues 566:587 The expressions and activities of the enzymes catalyzing O-GlcNAc cycling are several-fold higher in the brain than in the peripheral tissues. 27126545 7 18 theme O-GlcNAc 996:1003 arg1 elevation 977:985 pharmacological elevation 961:985 pharmacological elevation of brain O-GlcNAc 961:1003 Studies on mouse models of tauopathies suggest a neuroprotective role of pharmacological elevation of brain O-GlcNAc, which could potentially be a promising approach for treating AD and other neurodegenerative diseases. 27126545 2 19 from impact 249:254 arg1 phosphorylation 263:277 tau phosphorylation 259:277 tau phosphorylation 259:277 The discovery of O-GlcNAc modification of tau and its impact on tau phosphorylation has attracted recent research interest in O-GlcNAc studies in the Alzheimer's disease (AD) field. 27126545 5 20 theme O-GlcNAcylation 594:608 arg1 levels 610:615 The O-GlcNAcylation levels 590:615 The O-GlcNAcylation levels of brain proteins including tau 590:647 The O-GlcNAcylation levels of brain proteins including tau are decreased in AD brain, probably due to decreased brain glucose metabolism. 27126545 1 21 theme posttranslational 92:108 arg1 O-GlcNAcylation 69:83 O-GlcNAcylation 69:83 O-GlcNAcylation 69:83 O-GlcNAcylation is the posttranslational modification of intracellular proteins by O-linked β-N-acetylglucosamine (O-GlcNAc). 27126545 1 21 theme posttranslational 92:108 arg1 modification 110:121 the posttranslational modification 88:121 the posttranslational modification of intracellular proteins by O-linked β-N-acetylglucosamine (O-GlcNAc) 88:192 O-GlcNAcylation is the posttranslational modification of intracellular proteins by O-linked β-N-acetylglucosamine (O-GlcNAc). 27126545 2 22 from phosphorylation 263:277 arg1 discovery 199:207 The discovery 195:207 The discovery of O-GlcNAc modification of tau and its impact on tau phosphorylation 195:277 The discovery of O-GlcNAc modification of tau and its impact on tau phosphorylation has attracted recent research interest in O-GlcNAc studies in the Alzheimer's disease (AD) field. 27126545 7 23 theme elevation 977:985 arg1 role 953:956 a neuroprotective role 935:956 a neuroprotective role 935:956 Studies on mouse models of tauopathies suggest a neuroprotective role of pharmacological elevation of brain O-GlcNAc, which could potentially be a promising approach for treating AD and other neurodegenerative diseases. 27126545 7 23 theme elevation 977:985 arg1 approach 1045:1052 a promising approach 1033:1052 a promising approach for treating AD and other neurodegenerative diseases 1033:1105 Studies on mouse models of tauopathies suggest a neuroprotective role of pharmacological elevation of brain O-GlcNAc, which could potentially be a promising approach for treating AD and other neurodegenerative diseases. 27126545 5 24 theme glucose 708:714 arg1 metabolism 716:725 decreased brain glucose metabolism 692:725 decreased brain glucose metabolism 692:725 The O-GlcNAcylation levels of brain proteins including tau are decreased in AD brain, probably due to decreased brain glucose metabolism. 27126545 6 25 theme molecular 790:798 arg1 mechanism 800:808 the molecular mechanism 786:808 the molecular mechanism by which decreased brain glucose metabolism contributes to neurodegeneration 786:885 The reduction of brain O-GlcNAcylation appears to mediate the molecular mechanism by which decreased brain glucose metabolism contributes to neurodegeneration. 27126545 2 26 theme O-GlcNAc 321:328 arg1 studies 330:336 O-GlcNAc studies 321:336 O-GlcNAc studies in the Alzheimer's disease (AD) field 321:374 The discovery of O-GlcNAc modification of tau and its impact on tau phosphorylation has attracted recent research interest in O-GlcNAc studies in the Alzheimer's disease (AD) field. 27126545 2 27 theme disease 357:363 arg1 field 370:374 the Alzheimer's disease (AD) field 341:374 the Alzheimer's disease (AD) field 341:374 The discovery of O-GlcNAc modification of tau and its impact on tau phosphorylation has attracted recent research interest in O-GlcNAc studies in the Alzheimer's disease (AD) field. 27126545 2 28 theme impact 249:254 arg1 discovery 199:207 The discovery 195:207 The discovery of O-GlcNAc modification of tau and its impact on tau phosphorylation 195:277 The discovery of O-GlcNAc modification of tau and its impact on tau phosphorylation has attracted recent research interest in O-GlcNAc studies in the Alzheimer's disease (AD) field. 27126545 6 29 theme brain 829:833 arg1 metabolism 843:852 decreased brain glucose metabolism 819:852 decreased brain glucose metabolism 819:852 The reduction of brain O-GlcNAcylation appears to mediate the molecular mechanism by which decreased brain glucose metabolism contributes to neurodegeneration. 27126545 7 30 theme other 1074:1078 arg1 diseases 1098:1105 other neurodegenerative diseases 1074:1105 other neurodegenerative diseases 1074:1105 Studies on mouse models of tauopathies suggest a neuroprotective role of pharmacological elevation of brain O-GlcNAc, which could potentially be a promising approach for treating AD and other neurodegenerative diseases. 27126545 1 31 theme intracellular 126:138 arg1 proteins 140:147 intracellular proteins 126:147 intracellular proteins 126:147 O-GlcNAcylation is the posttranslational modification of intracellular proteins by O-linked β-N-acetylglucosamine (O-GlcNAc). 27126545 1 32 link O-linked 152:159 arg1 O-GlcNAc 184:191 O-GlcNAc 184:191 O-GlcNAc 184:191 O-GlcNAcylation is the posttranslational modification of intracellular proteins by O-linked β-N-acetylglucosamine (O-GlcNAc). 27126545 1 32 link O-linked 152:159 arg1 β-N-acetylglucosamine 161:181 O-linked β-N-acetylglucosamine 152:181 O-linked β-N-acetylglucosamine (O-GlcNAc) 152:192 O-GlcNAcylation is the posttranslational modification of intracellular proteins by O-linked β-N-acetylglucosamine (O-GlcNAc). 27126545 2 33 theme tau 237:239 arg1 discovery 199:207 The discovery 195:207 The discovery of O-GlcNAc modification of tau and its impact on tau phosphorylation 195:277 The discovery of O-GlcNAc modification of tau and its impact on tau phosphorylation has attracted recent research interest in O-GlcNAc studies in the Alzheimer's disease (AD) field. 27126545 1 34 theme proteins 140:147 arg1 O-GlcNAcylation 69:83 O-GlcNAcylation 69:83 O-GlcNAcylation 69:83 O-GlcNAcylation is the posttranslational modification of intracellular proteins by O-linked β-N-acetylglucosamine (O-GlcNAc). 27126545 1 34 theme proteins 140:147 arg1 modification 110:121 the posttranslational modification 88:121 the posttranslational modification of intracellular proteins by O-linked β-N-acetylglucosamine (O-GlcNAc) 88:192 O-GlcNAcylation is the posttranslational modification of intracellular proteins by O-linked β-N-acetylglucosamine (O-GlcNAc). 27126545 0 35 dep O-GlcNAcylation 0:14 arg1 regulator 19:27 A regulator 17:27 O-GlcNAcylation: A regulator of tau pathology and neurodegeneration. 0:67 O-GlcNAcylation: A regulator of tau pathology and neurodegeneration. 27126545 5 36 theme decreased 692:700 arg1 metabolism 716:725 decreased brain glucose metabolism 692:725 decreased brain glucose metabolism 692:725 The O-GlcNAcylation levels of brain proteins including tau are decreased in AD brain, probably due to decreased brain glucose metabolism. 27126545 7 37 from Studies 888:894 arg1 models 905:910 mouse models 899:910 mouse models of tauopathies 899:925 Studies on mouse models of tauopathies suggest a neuroprotective role of pharmacological elevation of brain O-GlcNAc, which could potentially be a promising approach for treating AD and other neurodegenerative diseases. 27126545 6 38 theme glucose 835:841 arg1 metabolism 843:852 decreased brain glucose metabolism 819:852 decreased brain glucose metabolism 819:852 The reduction of brain O-GlcNAcylation appears to mediate the molecular mechanism by which decreased brain glucose metabolism contributes to neurodegeneration. 27126545 7 39 theme pharmacological 961:975 arg1 elevation 977:985 pharmacological elevation 961:985 pharmacological elevation of brain O-GlcNAc 961:1003 Studies on mouse models of tauopathies suggest a neuroprotective role of pharmacological elevation of brain O-GlcNAc, which could potentially be a promising approach for treating AD and other neurodegenerative diseases. 27126545 5 40 theme brain 702:706 arg1 metabolism 716:725 decreased brain glucose metabolism 692:725 decreased brain glucose metabolism 692:725 The O-GlcNAcylation levels of brain proteins including tau are decreased in AD brain, probably due to decreased brain glucose metabolism. 27126545 2 41 theme modification 221:232 arg1 discovery 199:207 The discovery 195:207 The discovery of O-GlcNAc modification of tau and its impact on tau phosphorylation 195:277 The discovery of O-GlcNAc modification of tau and its impact on tau phosphorylation has attracted recent research interest in O-GlcNAc studies in the Alzheimer's disease (AD) field. 27126545 6 42 theme O-GlcNAcylation 751:765 arg1 reduction 732:740 The reduction 728:740 The reduction of brain O-GlcNAcylation 728:765 The reduction of brain O-GlcNAcylation appears to mediate the molecular mechanism by which decreased brain glucose metabolism contributes to neurodegeneration. 27126545 1 43 theme O-linked 152:159 arg1 O-GlcNAc 184:191 O-GlcNAc 184:191 O-GlcNAc 184:191 O-GlcNAcylation is the posttranslational modification of intracellular proteins by O-linked β-N-acetylglucosamine (O-GlcNAc). 27126545 1 43 theme O-linked 152:159 arg1 β-N-acetylglucosamine 161:181 O-linked β-N-acetylglucosamine 152:181 O-linked β-N-acetylglucosamine (O-GlcNAc) 152:192 O-GlcNAcylation is the posttranslational modification of intracellular proteins by O-linked β-N-acetylglucosamine (O-GlcNAc). 27126545 7 44 theme neuroprotective 937:951 arg1 role 953:956 a neuroprotective role 935:956 a neuroprotective role 935:956 Studies on mouse models of tauopathies suggest a neuroprotective role of pharmacological elevation of brain O-GlcNAc, which could potentially be a promising approach for treating AD and other neurodegenerative diseases. 27126545 7 44 theme neuroprotective 937:951 arg1 approach 1045:1052 a promising approach 1033:1052 a promising approach for treating AD and other neurodegenerative diseases 1033:1105 Studies on mouse models of tauopathies suggest a neuroprotective role of pharmacological elevation of brain O-GlcNAc, which could potentially be a promising approach for treating AD and other neurodegenerative diseases. 27126545 2 45 theme O-GlcNAc 212:219 arg1 modification 221:232 O-GlcNAc modification 212:232 O-GlcNAc modification 212:232 The discovery of O-GlcNAc modification of tau and its impact on tau phosphorylation has attracted recent research interest in O-GlcNAc studies in the Alzheimer's disease (AD) field. 27126545 6 46 theme brain 745:749 arg1 O-GlcNAcylation 751:765 brain O-GlcNAcylation 745:765 brain O-GlcNAcylation 745:765 The reduction of brain O-GlcNAcylation appears to mediate the molecular mechanism by which decreased brain glucose metabolism contributes to neurodegeneration. 27126545 2 47 theme tau 259:261 arg1 phosphorylation 263:277 tau phosphorylation 259:277 tau phosphorylation 259:277 The discovery of O-GlcNAc modification of tau and its impact on tau phosphorylation has attracted recent research interest in O-GlcNAc studies in the Alzheimer's disease (AD) field. 27126545 2 48 from studies 330:336 arg1 field 370:374 the Alzheimer's disease (AD) field 341:374 the Alzheimer's disease (AD) field 341:374 The discovery of O-GlcNAc modification of tau and its impact on tau phosphorylation has attracted recent research interest in O-GlcNAc studies in the Alzheimer's disease (AD) field. 27680668 5 0 theme antibody 750:757 arg1 reactivity 759:768 antibody reactivity 750:768 antibody reactivity 750:768 Sialidase treatment caused a dramatic increase in antibody reactivity in human pericardium, splenic capsule and trabeculae, plasma, serum, eye sleep extract, and liver sinusoids. 27680668 7 1 theme mucin 1181:1185 arg1 domain 1187:1192 the mucin domain 1177:1192 the mucin domain 1177:1192 These observations suggest that the origin of lubricin in blood may be different from that in synovial fluid and that desialylation of lubricin is essential for unmasking epitopes within the mucin domain. 27680668 7 2 theme synovial 1084:1091 arg1 fluid 1093:1097 synovial fluid 1084:1097 synovial fluid 1084:1097 These observations suggest that the origin of lubricin in blood may be different from that in synovial fluid and that desialylation of lubricin is essential for unmasking epitopes within the mucin domain. 27680668 4 3 theme S6.79 673:677 arg1 antibody 690:697 the S6.79 monoclonal antibody 669:697 the S6.79 monoclonal antibody 669:697 Our aim was to determine whether removal of sialic acid by sialidase could improve the detection of lubricin in a number of human tissues using the S6.79 monoclonal antibody. 27680668 5 4 theme dramatic 729:736 arg1 increase 738:745 a dramatic increase 727:745 a dramatic increase in antibody reactivity in human pericardium, splenic capsule and trabeculae, plasma, serum, eye sleep extract, and liver sinusoids 727:876 Sialidase treatment caused a dramatic increase in antibody reactivity in human pericardium, splenic capsule and trabeculae, plasma, serum, eye sleep extract, and liver sinusoids. 27680668 4 5 theme sialic 569:574 arg1 acid 576:579 sialic acid 569:579 sialic acid 569:579 Our aim was to determine whether removal of sialic acid by sialidase could improve the detection of lubricin in a number of human tissues using the S6.79 monoclonal antibody. 27680668 7 6 from that 1076:1079 arg1 different 1061:1069 different 1061:1069 different 1061:1069 These observations suggest that the origin of lubricin in blood may be different from that in synovial fluid and that desialylation of lubricin is essential for unmasking epitopes within the mucin domain. 27680668 7 6 from that 1076:1079 arg1 origin 1026:1031 the origin 1022:1031 the origin of lubricin in blood 1022:1052 These observations suggest that the origin of lubricin in blood may be different from that in synovial fluid and that desialylation of lubricin is essential for unmasking epitopes within the mucin domain. 27680668 1 7 theme boundary 159:166 arg1 lubrication 168:178 boundary lubrication 159:178 boundary lubrication 159:178 Lubricin is a secreted, mucin-like glycoprotein and proteoglycan abundant in synovial fluid that provides boundary lubrication and prevents cell adhesion in synovial joints. 27680668 6 8 theme synovial 954:961 arg1 fluid 963:967 synovial fluid 954:967 synovial fluid 954:967 Sialidase had minimal effect on S6.79 antibody reactivity with lubricin in synovial fluid and synovial tissue. 27680668 1 9 from fluid 139:143 arg1 abundant 118:125 abundant 118:125 abundant 118:125 Lubricin is a secreted, mucin-like glycoprotein and proteoglycan abundant in synovial fluid that provides boundary lubrication and prevents cell adhesion in synovial joints. 27680668 5 10 theme liver 862:866 arg1 sinusoids 868:876 liver sinusoids 862:876 liver sinusoids 862:876 Sialidase treatment caused a dramatic increase in antibody reactivity in human pericardium, splenic capsule and trabeculae, plasma, serum, eye sleep extract, and liver sinusoids. 27680668 3 11 theme O-glycosylated 475:488 arg1 sites 490:494 the O-glycosylated sites 471:494 the O-glycosylated sites 471:494 The central, long mucin domain of lubricin is extensively O-glycosylated with Gal(β1-3)GalNAc-O-Ser/Thr, and about two thirds of the O-glycosylated sites are capped with sialic acid. 27680668 3 12 gly O-glycosylated 400:413 arg1 lubricin 376:383 lubricin 376:383 lubricin 376:383 The central, long mucin domain of lubricin is extensively O-glycosylated with Gal(β1-3)GalNAc-O-Ser/Thr, and about two thirds of the O-glycosylated sites are capped with sialic acid. 27680668 3 12 gly O-glycosylated 400:413 arg1 O-glycosylated 400:413 O-glycosylated 400:413 O-glycosylated 400:413 The central, long mucin domain of lubricin is extensively O-glycosylated with Gal(β1-3)GalNAc-O-Ser/Thr, and about two thirds of the O-glycosylated sites are capped with sialic acid. 27680668 3 12 gly O-glycosylated 400:413 arg1 domain 366:371 The central, long mucin domain 342:371 The central, long mucin domain of lubricin 342:383 The central, long mucin domain of lubricin is extensively O-glycosylated with Gal(β1-3)GalNAc-O-Ser/Thr, and about two thirds of the O-glycosylated sites are capped with sialic acid. 27680668 2 13 theme glycopeptide 293:304 arg1 epitope 306:312 an O-linked glycopeptide epitope 281:312 an O-linked glycopeptide epitope in lubricin's mucin domain 281:339 The antilubricin S6.79 monoclonal antibody recognizes an O-linked glycopeptide epitope in lubricin's mucin domain. 27680668 5 14 theme sleep 843:847 arg1 extract 849:855 eye sleep extract 839:855 eye sleep extract 839:855 Sialidase treatment caused a dramatic increase in antibody reactivity in human pericardium, splenic capsule and trabeculae, plasma, serum, eye sleep extract, and liver sinusoids. 27680668 5 15 theme human 773:777 arg1 pericardium 779:789 human pericardium 773:789 human pericardium 773:789 Sialidase treatment caused a dramatic increase in antibody reactivity in human pericardium, splenic capsule and trabeculae, plasma, serum, eye sleep extract, and liver sinusoids. 27680668 1 16 gly glycoprotein 88:99 arg1 Lubricin 53:60 Lubricin 53:60 Lubricin 53:60 Lubricin is a secreted, mucin-like glycoprotein and proteoglycan abundant in synovial fluid that provides boundary lubrication and prevents cell adhesion in synovial joints. 27680668 1 16 gly glycoprotein 88:99 arg1 glycoprotein 88:99 a secreted, mucin-like glycoprotein 65:99 glycoprotein 88:99 Lubricin is a secreted, mucin-like glycoprotein and proteoglycan abundant in synovial fluid that provides boundary lubrication and prevents cell adhesion in synovial joints. 27680668 6 17 theme synovial 973:980 arg1 tissue 982:987 synovial tissue 973:987 synovial tissue 973:987 Sialidase had minimal effect on S6.79 antibody reactivity with lubricin in synovial fluid and synovial tissue. 27680668 2 18 theme O-linked 284:291 arg1 epitope 306:312 an O-linked glycopeptide epitope 281:312 an O-linked glycopeptide epitope in lubricin's mucin domain 281:339 The antilubricin S6.79 monoclonal antibody recognizes an O-linked glycopeptide epitope in lubricin's mucin domain. 27680668 5 19 theme eye 839:841 arg1 extract 849:855 eye sleep extract 839:855 eye sleep extract 839:855 Sialidase treatment caused a dramatic increase in antibody reactivity in human pericardium, splenic capsule and trabeculae, plasma, serum, eye sleep extract, and liver sinusoids. 27680668 5 20 theme splenic 792:798 arg1 capsule 800:806 splenic capsule 792:806 splenic capsule 792:806 Sialidase treatment caused a dramatic increase in antibody reactivity in human pericardium, splenic capsule and trabeculae, plasma, serum, eye sleep extract, and liver sinusoids. 27680668 3 21 theme lubricin 376:383 arg1 lubricin 376:383 lubricin 376:383 lubricin 376:383 The central, long mucin domain of lubricin is extensively O-glycosylated with Gal(β1-3)GalNAc-O-Ser/Thr, and about two thirds of the O-glycosylated sites are capped with sialic acid. 27680668 3 21 theme lubricin 376:383 arg1 O-glycosylated 400:413 O-glycosylated 400:413 O-glycosylated 400:413 The central, long mucin domain of lubricin is extensively O-glycosylated with Gal(β1-3)GalNAc-O-Ser/Thr, and about two thirds of the O-glycosylated sites are capped with sialic acid. 27680668 3 21 theme lubricin 376:383 arg1 domain 366:371 The central, long mucin domain 342:371 The central, long mucin domain of lubricin 342:383 The central, long mucin domain of lubricin is extensively O-glycosylated with Gal(β1-3)GalNAc-O-Ser/Thr, and about two thirds of the O-glycosylated sites are capped with sialic acid. 27680668 4 22 theme human 649:653 arg1 tissues 655:661 human tissues 649:661 human tissues using the S6.79 monoclonal antibody 649:697 Our aim was to determine whether removal of sialic acid by sialidase could improve the detection of lubricin in a number of human tissues using the S6.79 monoclonal antibody. 27680668 7 23 theme lubricin 1036:1043 arg1 different 1061:1069 different 1061:1069 different 1061:1069 These observations suggest that the origin of lubricin in blood may be different from that in synovial fluid and that desialylation of lubricin is essential for unmasking epitopes within the mucin domain. 27680668 7 23 theme lubricin 1036:1043 arg1 origin 1026:1031 the origin 1022:1031 the origin of lubricin in blood 1022:1052 These observations suggest that the origin of lubricin in blood may be different from that in synovial fluid and that desialylation of lubricin is essential for unmasking epitopes within the mucin domain. 27680668 2 24 theme mucin 328:332 arg1 domain 334:339 lubricin's mucin domain 317:339 lubricin's mucin domain 317:339 The antilubricin S6.79 monoclonal antibody recognizes an O-linked glycopeptide epitope in lubricin's mucin domain. 27680668 1 25 theme cell 193:196 arg1 adhesion 198:205 cell adhesion 193:205 cell adhesion in synovial joints 193:224 Lubricin is a secreted, mucin-like glycoprotein and proteoglycan abundant in synovial fluid that provides boundary lubrication and prevents cell adhesion in synovial joints. 27680668 0 26 theme Domain 24:29 arg1 Epitopes 31:38 Mucin Domain Epitopes 18:38 Mucin Domain Epitopes of Lubricin 18:50 Sialidase Unmasks Mucin Domain Epitopes of Lubricin. 27680668 2 27 link O-linked 284:291 arg1 epitope 306:312 an O-linked glycopeptide epitope 281:312 an O-linked glycopeptide epitope in lubricin's mucin domain 281:339 The antilubricin S6.79 monoclonal antibody recognizes an O-linked glycopeptide epitope in lubricin's mucin domain. 27680668 1 28 from abundant 118:125 arg1 fluid 139:143 synovial fluid 130:143 synovial fluid 130:143 Lubricin is a secreted, mucin-like glycoprotein and proteoglycan abundant in synovial fluid that provides boundary lubrication and prevents cell adhesion in synovial joints. 27680668 3 29 gly O-glycosylated 475:488 arg1 sites 490:494 the O-glycosylated sites 471:494 the O-glycosylated sites 471:494 The central, long mucin domain of lubricin is extensively O-glycosylated with Gal(β1-3)GalNAc-O-Ser/Thr, and about two thirds of the O-glycosylated sites are capped with sialic acid. 27680668 1 30 theme mucin-like 77:86 arg1 Lubricin 53:60 Lubricin 53:60 Lubricin 53:60 Lubricin is a secreted, mucin-like glycoprotein and proteoglycan abundant in synovial fluid that provides boundary lubrication and prevents cell adhesion in synovial joints. 27680668 1 30 theme mucin-like 77:86 arg1 glycoprotein 88:99 a secreted, mucin-like glycoprotein 65:99 glycoprotein 88:99 Lubricin is a secreted, mucin-like glycoprotein and proteoglycan abundant in synovial fluid that provides boundary lubrication and prevents cell adhesion in synovial joints. 27680668 3 31 with O-glycosylated 400:413 arg1 GalNAc-O-Ser/Thr 429:444 GalNAc-O-Ser/Thr 429:444 GalNAc-O-Ser/Thr 429:444 The central, long mucin domain of lubricin is extensively O-glycosylated with Gal(β1-3)GalNAc-O-Ser/Thr, and about two thirds of the O-glycosylated sites are capped with sialic acid. 27680668 6 32 from lubricin 942:949 arg1 fluid 963:967 synovial fluid 954:967 synovial fluid 954:967 Sialidase had minimal effect on S6.79 antibody reactivity with lubricin in synovial fluid and synovial tissue. 27680668 6 32 from lubricin 942:949 arg1 tissue 982:987 synovial tissue 973:987 synovial tissue 973:987 Sialidase had minimal effect on S6.79 antibody reactivity with lubricin in synovial fluid and synovial tissue. 27680668 4 33 theme monoclonal 679:688 arg1 antibody 690:697 the S6.79 monoclonal antibody 669:697 the S6.79 monoclonal antibody 669:697 Our aim was to determine whether removal of sialic acid by sialidase could improve the detection of lubricin in a number of human tissues using the S6.79 monoclonal antibody. 27680668 3 34 dep central 346:352 arg1 long 355:358 long 355:358 long 355:358 The central, long mucin domain of lubricin is extensively O-glycosylated with Gal(β1-3)GalNAc-O-Ser/Thr, and about two thirds of the O-glycosylated sites are capped with sialic acid. 27680668 2 35 theme S6.79 244:248 arg1 antibody 261:268 The antilubricin S6.79 monoclonal antibody 227:268 The antilubricin S6.79 monoclonal antibody 227:268 The antilubricin S6.79 monoclonal antibody recognizes an O-linked glycopeptide epitope in lubricin's mucin domain. 27680668 4 36 from detection 612:620 arg1 number 639:644 a number 637:644 a number of human tissues using the S6.79 monoclonal antibody 637:697 Our aim was to determine whether removal of sialic acid by sialidase could improve the detection of lubricin in a number of human tissues using the S6.79 monoclonal antibody. 27680668 1 37 theme synovial 210:217 arg1 joints 219:224 synovial joints 210:224 synovial joints 210:224 Lubricin is a secreted, mucin-like glycoprotein and proteoglycan abundant in synovial fluid that provides boundary lubrication and prevents cell adhesion in synovial joints. 27680668 0 38 theme Mucin 18:22 arg1 Epitopes 31:38 Mucin Domain Epitopes 18:38 Mucin Domain Epitopes of Lubricin 18:50 Sialidase Unmasks Mucin Domain Epitopes of Lubricin. 27680668 6 39 theme antibody 917:924 arg1 reactivity 926:935 S6.79 antibody reactivity 911:935 S6.79 antibody reactivity with lubricin in synovial fluid and synovial tissue 911:987 Sialidase had minimal effect on S6.79 antibody reactivity with lubricin in synovial fluid and synovial tissue. 27680668 5 40 theme Sialidase 700:708 arg1 treatment 710:718 Sialidase treatment 700:718 Sialidase treatment 700:718 Sialidase treatment caused a dramatic increase in antibody reactivity in human pericardium, splenic capsule and trabeculae, plasma, serum, eye sleep extract, and liver sinusoids. 27680668 2 41 theme antilubricin 231:242 arg1 antibody 261:268 The antilubricin S6.79 monoclonal antibody 227:268 The antilubricin S6.79 monoclonal antibody 227:268 The antilubricin S6.79 monoclonal antibody recognizes an O-linked glycopeptide epitope in lubricin's mucin domain. 27680668 2 42 gly glycopeptide 293:304 arg2 glycopeptide 293:304 an O-linked glycopeptide epitope 281:312 an O-linked glycopeptide epitope in lubricin's mucin domain 281:339 The antilubricin S6.79 monoclonal antibody recognizes an O-linked glycopeptide epitope in lubricin's mucin domain. 27680668 6 43 theme S6.79 911:915 arg1 reactivity 926:935 S6.79 antibody reactivity 911:935 S6.79 antibody reactivity with lubricin in synovial fluid and synovial tissue 911:987 Sialidase had minimal effect on S6.79 antibody reactivity with lubricin in synovial fluid and synovial tissue. 27680668 3 44 theme sites 490:494 arg1 thirds 461:466 about two thirds 451:466 about two thirds of the O-glycosylated sites 451:494 The central, long mucin domain of lubricin is extensively O-glycosylated with Gal(β1-3)GalNAc-O-Ser/Thr, and about two thirds of the O-glycosylated sites are capped with sialic acid. 27680668 0 45 theme Lubricin 43:50 arg1 Epitopes 31:38 Mucin Domain Epitopes 18:38 Mucin Domain Epitopes of Lubricin 18:50 Sialidase Unmasks Mucin Domain Epitopes of Lubricin. 27680668 3 46 theme mucin 360:364 arg1 lubricin 376:383 lubricin 376:383 lubricin 376:383 The central, long mucin domain of lubricin is extensively O-glycosylated with Gal(β1-3)GalNAc-O-Ser/Thr, and about two thirds of the O-glycosylated sites are capped with sialic acid. 27680668 3 46 theme mucin 360:364 arg1 O-glycosylated 400:413 O-glycosylated 400:413 O-glycosylated 400:413 The central, long mucin domain of lubricin is extensively O-glycosylated with Gal(β1-3)GalNAc-O-Ser/Thr, and about two thirds of the O-glycosylated sites are capped with sialic acid. 27680668 3 46 theme mucin 360:364 arg1 domain 366:371 The central, long mucin domain 342:371 The central, long mucin domain of lubricin 342:383 The central, long mucin domain of lubricin is extensively O-glycosylated with Gal(β1-3)GalNAc-O-Ser/Thr, and about two thirds of the O-glycosylated sites are capped with sialic acid. 27680668 1 47 from adhesion 198:205 arg1 joints 219:224 synovial joints 210:224 synovial joints 210:224 Lubricin is a secreted, mucin-like glycoprotein and proteoglycan abundant in synovial fluid that provides boundary lubrication and prevents cell adhesion in synovial joints. 27680668 1 48 theme abundant 118:125 arg1 Lubricin 53:60 Lubricin 53:60 Lubricin 53:60 Lubricin is a secreted, mucin-like glycoprotein and proteoglycan abundant in synovial fluid that provides boundary lubrication and prevents cell adhesion in synovial joints. 27680668 1 48 theme abundant 118:125 arg1 glycoprotein 88:99 a secreted, mucin-like glycoprotein 65:99 glycoprotein 88:99 Lubricin is a secreted, mucin-like glycoprotein and proteoglycan abundant in synovial fluid that provides boundary lubrication and prevents cell adhesion in synovial joints. 27680668 7 49 gly desialylation 1108:1120 arg1 lubricin 1125:1132 lubricin 1125:1132 lubricin 1125:1132 These observations suggest that the origin of lubricin in blood may be different from that in synovial fluid and that desialylation of lubricin is essential for unmasking epitopes within the mucin domain. 27680668 7 50 theme lubricin 1125:1132 arg1 desialylation 1108:1120 desialylation 1108:1120 desialylation of lubricin 1108:1132 These observations suggest that the origin of lubricin in blood may be different from that in synovial fluid and that desialylation of lubricin is essential for unmasking epitopes within the mucin domain. 27680668 6 51 with reactivity 926:935 arg1 lubricin 942:949 lubricin 942:949 lubricin in synovial fluid and synovial tissue 942:987 Sialidase had minimal effect on S6.79 antibody reactivity with lubricin in synovial fluid and synovial tissue. 27680668 6 52 contain had 889:891 arg1 Sialidase 879:887 Sialidase 879:887 Sialidase 879:887 Sialidase had minimal effect on S6.79 antibody reactivity with lubricin in synovial fluid and synovial tissue. 27680668 6 52 contain had 889:891 arg2 effect 901:906 minimal effect 893:906 minimal effect 893:906 Sialidase had minimal effect on S6.79 antibody reactivity with lubricin in synovial fluid and synovial tissue. 27680668 1 53 theme secreted 67:74 arg1 Lubricin 53:60 Lubricin 53:60 Lubricin 53:60 Lubricin is a secreted, mucin-like glycoprotein and proteoglycan abundant in synovial fluid that provides boundary lubrication and prevents cell adhesion in synovial joints. 27680668 1 53 theme secreted 67:74 arg1 glycoprotein 88:99 a secreted, mucin-like glycoprotein 65:99 glycoprotein 88:99 Lubricin is a secreted, mucin-like glycoprotein and proteoglycan abundant in synovial fluid that provides boundary lubrication and prevents cell adhesion in synovial joints. 27680668 5 54 from increase 738:745 arg1 pericardium 779:789 human pericardium 773:789 human pericardium 773:789 Sialidase treatment caused a dramatic increase in antibody reactivity in human pericardium, splenic capsule and trabeculae, plasma, serum, eye sleep extract, and liver sinusoids. 27680668 5 54 from increase 738:745 arg1 capsule 800:806 splenic capsule 792:806 splenic capsule 792:806 Sialidase treatment caused a dramatic increase in antibody reactivity in human pericardium, splenic capsule and trabeculae, plasma, serum, eye sleep extract, and liver sinusoids. 27680668 5 54 from increase 738:745 arg1 reactivity 759:768 antibody reactivity 750:768 antibody reactivity 750:768 Sialidase treatment caused a dramatic increase in antibody reactivity in human pericardium, splenic capsule and trabeculae, plasma, serum, eye sleep extract, and liver sinusoids. 27680668 5 54 from increase 738:745 arg1 trabeculae 812:821 trabeculae 812:821 trabeculae 812:821 Sialidase treatment caused a dramatic increase in antibody reactivity in human pericardium, splenic capsule and trabeculae, plasma, serum, eye sleep extract, and liver sinusoids. 27680668 1 55 theme synovial 130:137 arg1 fluid 139:143 synovial fluid 130:143 synovial fluid 130:143 Lubricin is a secreted, mucin-like glycoprotein and proteoglycan abundant in synovial fluid that provides boundary lubrication and prevents cell adhesion in synovial joints. 27680668 3 56 theme central 346:352 arg1 lubricin 376:383 lubricin 376:383 lubricin 376:383 The central, long mucin domain of lubricin is extensively O-glycosylated with Gal(β1-3)GalNAc-O-Ser/Thr, and about two thirds of the O-glycosylated sites are capped with sialic acid. 27680668 3 56 theme central 346:352 arg1 O-glycosylated 400:413 O-glycosylated 400:413 O-glycosylated 400:413 The central, long mucin domain of lubricin is extensively O-glycosylated with Gal(β1-3)GalNAc-O-Ser/Thr, and about two thirds of the O-glycosylated sites are capped with sialic acid. 27680668 3 56 theme central 346:352 arg1 domain 366:371 The central, long mucin domain 342:371 The central, long mucin domain of lubricin 342:383 The central, long mucin domain of lubricin is extensively O-glycosylated with Gal(β1-3)GalNAc-O-Ser/Thr, and about two thirds of the O-glycosylated sites are capped with sialic acid. 27680668 4 57 theme lubricin 625:632 arg1 detection 612:620 the detection 608:620 the detection of lubricin in a number of human tissues using the S6.79 monoclonal antibody 608:697 Our aim was to determine whether removal of sialic acid by sialidase could improve the detection of lubricin in a number of human tissues using the S6.79 monoclonal antibody. 27680668 3 58 theme sialic 512:517 arg1 acid 519:522 sialic acid 512:522 sialic acid 512:522 The central, long mucin domain of lubricin is extensively O-glycosylated with Gal(β1-3)GalNAc-O-Ser/Thr, and about two thirds of the O-glycosylated sites are capped with sialic acid. 27680668 2 59 from epitope 306:312 arg1 domain 334:339 lubricin's mucin domain 317:339 lubricin's mucin domain 317:339 The antilubricin S6.79 monoclonal antibody recognizes an O-linked glycopeptide epitope in lubricin's mucin domain. 27680668 4 60 theme acid 576:579 arg1 removal 558:564 removal 558:564 removal of sialic acid by sialidase 558:592 Our aim was to determine whether removal of sialic acid by sialidase could improve the detection of lubricin in a number of human tissues using the S6.79 monoclonal antibody. 27680668 6 61 theme minimal 893:899 arg1 effect 901:906 minimal effect 893:906 minimal effect 893:906 Sialidase had minimal effect on S6.79 antibody reactivity with lubricin in synovial fluid and synovial tissue. 27680668 2 62 theme monoclonal 250:259 arg1 antibody 261:268 The antilubricin S6.79 monoclonal antibody 227:268 The antilubricin S6.79 monoclonal antibody 227:268 The antilubricin S6.79 monoclonal antibody recognizes an O-linked glycopeptide epitope in lubricin's mucin domain. 27680668 4 63 theme tissues 655:661 arg1 number 639:644 a number 637:644 a number of human tissues using the S6.79 monoclonal antibody 637:697 Our aim was to determine whether removal of sialic acid by sialidase could improve the detection of lubricin in a number of human tissues using the S6.79 monoclonal antibody. 27680668 7 64 from origin 1026:1031 arg1 blood 1048:1052 blood 1048:1052 blood 1048:1052 These observations suggest that the origin of lubricin in blood may be different from that in synovial fluid and that desialylation of lubricin is essential for unmasking epitopes within the mucin domain. 24528746 5 0 theme hemagglutination 683:698 arg1 sulfates 723:730 hemagglutination and adhesion indicated sulfates 683:730 hemagglutination and adhesion indicated sulfates 683:730 Inhibition assay of hemagglutination and adhesion indicated sulfates prevented H. pylori from adhering to erythrocytes and AGS cells. 24528746 3 1 theme elemental 501:509 arg1 analysis 511:518 elemental analysis 501:518 elemental analysis 501:518 The introduction of sulfates was characterized using FT-IR and elemental analysis. 24528746 8 2 theme H. 1171:1172 arg1 adhesions 1158:1166 adhesions 1158:1166 adhesions of H. pylori 1158:1179 Thus polysaccharide sulfates can serve as potential adjuvants to raise the bacterial eradication rate by inhibiting adhesions of H. pylori. 24528746 7 3 theme sulfates 1010:1017 arg1 content 971:977 A higher content 962:977 A higher content of galactoses and 2,3-O-linked sulfates 962:1017 A higher content of galactoses and 2,3-O-linked sulfates benefited this action. 24528746 4 4 theme rheological 585:595 arg1 property 597:604 rheological property 585:604 rheological property 585:604 Data from zeta-potential, hydrodynamic diameter, hydrolysis and rheological property demonstrated the sulfates were physicochemically stable. 24528746 7 5 theme galactoses 982:991 arg1 content 971:977 A higher content 962:977 A higher content of galactoses and 2,3-O-linked sulfates 962:1017 A higher content of galactoses and 2,3-O-linked sulfates benefited this action. 24528746 5 6 theme adhesion 704:711 arg1 sulfates 723:730 hemagglutination and adhesion indicated sulfates 683:730 hemagglutination and adhesion indicated sulfates 683:730 Inhibition assay of hemagglutination and adhesion indicated sulfates prevented H. pylori from adhering to erythrocytes and AGS cells. 24528746 1 7 theme Helicobacter 116:127 arg1 infections 136:145 Helicobacter pylori infections 116:145 Helicobacter pylori infections 116:145 In treatments of Helicobacter pylori infections, recrudescences were common because of an unfavorable bacterial eradication rate due to the ever increasing resistance to antibiotics. 24528746 5 8 theme AGS 786:788 arg1 cells 790:794 AGS cells 786:794 AGS cells 786:794 Inhibition assay of hemagglutination and adhesion indicated sulfates prevented H. pylori from adhering to erythrocytes and AGS cells. 24528746 5 9 theme indicated 713:721 arg1 sulfates 723:730 hemagglutination and adhesion indicated sulfates 683:730 hemagglutination and adhesion indicated sulfates 683:730 Inhibition assay of hemagglutination and adhesion indicated sulfates prevented H. pylori from adhering to erythrocytes and AGS cells. 24528746 8 10 theme potential 1084:1092 arg1 adjuvants 1094:1102 potential adjuvants 1084:1102 potential adjuvants 1084:1102 Thus polysaccharide sulfates can serve as potential adjuvants to raise the bacterial eradication rate by inhibiting adhesions of H. pylori. 24528746 8 10 theme potential 1084:1092 arg1 sulfates 1062:1069 polysaccharide sulfates 1047:1069 polysaccharide sulfates 1047:1069 Thus polysaccharide sulfates can serve as potential adjuvants to raise the bacterial eradication rate by inhibiting adhesions of H. pylori. 24528746 4 11 from property 597:604 arg1 Data 521:524 Data 521:524 Data from zeta-potential, hydrodynamic diameter, hydrolysis and rheological property 521:604 Data from zeta-potential, hydrodynamic diameter, hydrolysis and rheological property demonstrated the sulfates were physicochemically stable. 24528746 6 12 theme bacterial 933:941 arg1 adhesion 943:950 the bacterial adhesion 929:950 the bacterial adhesion to hosts 929:959 In binding assay, affinities of sulfates to H. pylori suggested sulfates could compete with target cells for bacteria and moderated the bacterial adhesion to hosts. 24528746 1 13 from common 168:173 arg1 treatments 102:111 treatments 102:111 treatments of Helicobacter pylori infections 102:145 In treatments of Helicobacter pylori infections, recrudescences were common because of an unfavorable bacterial eradication rate due to the ever increasing resistance to antibiotics. 24528746 2 14 theme H. 389:390 arg1 adhesions 376:384 adhesions 376:384 adhesions of H. pylori 376:397 In this study, we chose pectin, guar gum and chitosan to synthesize their sulfates to inhibit adhesions of H. pylori and thus enhance the eradication rate. 24528746 5 15 theme Inhibition 663:672 arg1 assay 674:678 Inhibition assay 663:678 Inhibition assay of hemagglutination and adhesion indicated sulfates 663:730 Inhibition assay of hemagglutination and adhesion indicated sulfates prevented H. pylori from adhering to erythrocytes and AGS cells. 24528746 1 16 theme unfavorable 189:199 arg1 rate 223:226 an unfavorable bacterial eradication rate 186:226 an unfavorable bacterial eradication rate due to the ever increasing resistance to antibiotics 186:279 In treatments of Helicobacter pylori infections, recrudescences were common because of an unfavorable bacterial eradication rate due to the ever increasing resistance to antibiotics. 24528746 8 17 theme eradication 1127:1137 arg1 rate 1139:1142 the bacterial eradication rate 1113:1142 the bacterial eradication rate 1113:1142 Thus polysaccharide sulfates can serve as potential adjuvants to raise the bacterial eradication rate by inhibiting adhesions of H. pylori. 24528746 6 18 theme sulfates 829:836 arg1 affinities 815:824 affinities 815:824 affinities of sulfates to H. pylori 815:849 In binding assay, affinities of sulfates to H. pylori suggested sulfates could compete with target cells for bacteria and moderated the bacterial adhesion to hosts. 24528746 1 19 theme bacterial 201:209 arg1 rate 223:226 an unfavorable bacterial eradication rate 186:226 an unfavorable bacterial eradication rate due to the ever increasing resistance to antibiotics 186:279 In treatments of Helicobacter pylori infections, recrudescences were common because of an unfavorable bacterial eradication rate due to the ever increasing resistance to antibiotics. 24528746 4 20 from hydrolysis 570:579 arg1 Data 521:524 Data 521:524 Data from zeta-potential, hydrodynamic diameter, hydrolysis and rheological property 521:604 Data from zeta-potential, hydrodynamic diameter, hydrolysis and rheological property demonstrated the sulfates were physicochemically stable. 24528746 8 21 theme bacterial 1117:1125 arg1 rate 1139:1142 the bacterial eradication rate 1113:1142 the bacterial eradication rate 1113:1142 Thus polysaccharide sulfates can serve as potential adjuvants to raise the bacterial eradication rate by inhibiting adhesions of H. pylori. 24528746 7 22 theme higher 964:969 arg1 content 971:977 A higher content 962:977 A higher content of galactoses and 2,3-O-linked sulfates 962:1017 A higher content of galactoses and 2,3-O-linked sulfates benefited this action. 24528746 2 23 theme guar 314:317 arg1 gum 319:321 guar gum 314:321 guar gum 314:321 In this study, we chose pectin, guar gum and chitosan to synthesize their sulfates to inhibit adhesions of H. pylori and thus enhance the eradication rate. 24528746 1 24 theme eradication 211:221 arg1 rate 223:226 an unfavorable bacterial eradication rate 186:226 an unfavorable bacterial eradication rate due to the ever increasing resistance to antibiotics 186:279 In treatments of Helicobacter pylori infections, recrudescences were common because of an unfavorable bacterial eradication rate due to the ever increasing resistance to antibiotics. 24528746 7 25 theme 2,3-O-linked 997:1008 arg1 sulfates 1010:1017 2,3-O-linked sulfates 997:1017 2,3-O-linked sulfates 997:1017 A higher content of galactoses and 2,3-O-linked sulfates benefited this action. 24528746 6 26 dep H. 841:842 arg1 pylori 844:849 H. pylori 841:849 H. pylori 841:849 In binding assay, affinities of sulfates to H. pylori suggested sulfates could compete with target cells for bacteria and moderated the bacterial adhesion to hosts. 24528746 3 27 theme sulfates 458:465 arg1 introduction 442:453 The introduction 438:453 The introduction of sulfates 438:465 The introduction of sulfates was characterized using FT-IR and elemental analysis. 24528746 2 28 theme eradication 420:430 arg1 rate 432:435 the eradication rate 416:435 the eradication rate 416:435 In this study, we chose pectin, guar gum and chitosan to synthesize their sulfates to inhibit adhesions of H. pylori and thus enhance the eradication rate. 24528746 0 29 dep Helicobacter 69:80 arg1 pylori 82:87 pylori 82:87 pylori 82:87 Preparation and evaluation of polysaccharide sulfates for inhibiting Helicobacter pylori adhesion. 24528746 8 30 theme polysaccharide 1047:1060 arg1 adjuvants 1094:1102 potential adjuvants 1084:1102 potential adjuvants 1084:1102 Thus polysaccharide sulfates can serve as potential adjuvants to raise the bacterial eradication rate by inhibiting adhesions of H. pylori. 24528746 8 30 theme polysaccharide 1047:1060 arg1 sulfates 1062:1069 polysaccharide sulfates 1047:1069 polysaccharide sulfates 1047:1069 Thus polysaccharide sulfates can serve as potential adjuvants to raise the bacterial eradication rate by inhibiting adhesions of H. pylori. 24528746 4 31 dep demonstrated 606:617 arg1 stable 655:660 stable 655:660 stable 655:660 Data from zeta-potential, hydrodynamic diameter, hydrolysis and rheological property demonstrated the sulfates were physicochemically stable. 24528746 6 32 dep suggested 851:859 arg1 moderated 919:927 moderated 919:927 moderated the bacterial adhesion to hosts 919:959 In binding assay, affinities of sulfates to H. pylori suggested sulfates could compete with target cells for bacteria and moderated the bacterial adhesion to hosts. 24528746 6 32 dep suggested 851:859 arg1 compete 876:882 compete 876:882 could compete with target cells for bacteria 870:913 In binding assay, affinities of sulfates to H. pylori suggested sulfates could compete with target cells for bacteria and moderated the bacterial adhesion to hosts. 24528746 0 33 theme polysaccharide 30:43 arg1 evaluation 16:25 evaluation 16:25 evaluation 16:25 Preparation and evaluation of polysaccharide sulfates for inhibiting Helicobacter pylori adhesion. 24528746 0 33 theme polysaccharide 30:43 arg1 Preparation 0:10 Preparation 0:10 Preparation 0:10 Preparation and evaluation of polysaccharide sulfates for inhibiting Helicobacter pylori adhesion. 24528746 7 34 link 2,3-O-linked 997:1008 arg1 sulfates 1010:1017 2,3-O-linked sulfates 997:1017 2,3-O-linked sulfates 997:1017 A higher content of galactoses and 2,3-O-linked sulfates benefited this action. 24528746 4 35 from zeta-potential 531:544 arg1 Data 521:524 Data 521:524 Data from zeta-potential, hydrodynamic diameter, hydrolysis and rheological property 521:604 Data from zeta-potential, hydrodynamic diameter, hydrolysis and rheological property demonstrated the sulfates were physicochemically stable. 24528746 5 36 theme sulfates 723:730 arg1 assay 674:678 Inhibition assay 663:678 Inhibition assay of hemagglutination and adhesion indicated sulfates 663:730 Inhibition assay of hemagglutination and adhesion indicated sulfates prevented H. pylori from adhering to erythrocytes and AGS cells. 24528746 1 37 theme pylori 129:134 arg1 infections 136:145 Helicobacter pylori infections 116:145 Helicobacter pylori infections 116:145 In treatments of Helicobacter pylori infections, recrudescences were common because of an unfavorable bacterial eradication rate due to the ever increasing resistance to antibiotics. 24528746 4 38 theme hydrodynamic 547:558 arg1 diameter 560:567 hydrodynamic diameter 547:567 hydrodynamic diameter 547:567 Data from zeta-potential, hydrodynamic diameter, hydrolysis and rheological property demonstrated the sulfates were physicochemically stable. 24528746 6 39 theme target 889:894 arg1 cells 896:900 target cells 889:900 target cells 889:900 In binding assay, affinities of sulfates to H. pylori suggested sulfates could compete with target cells for bacteria and moderated the bacterial adhesion to hosts. 24528746 6 40 theme binding 800:806 arg1 assay 808:812 binding assay 800:812 binding assay 800:812 In binding assay, affinities of sulfates to H. pylori suggested sulfates could compete with target cells for bacteria and moderated the bacterial adhesion to hosts. 24528746 1 41 theme infections 136:145 arg1 treatments 102:111 treatments 102:111 treatments of Helicobacter pylori infections 102:145 In treatments of Helicobacter pylori infections, recrudescences were common because of an unfavorable bacterial eradication rate due to the ever increasing resistance to antibiotics. 24528746 4 42 from diameter 560:567 arg1 Data 521:524 Data 521:524 Data from zeta-potential, hydrodynamic diameter, hydrolysis and rheological property 521:604 Data from zeta-potential, hydrodynamic diameter, hydrolysis and rheological property demonstrated the sulfates were physicochemically stable. 24528746 1 43 theme increasing 244:253 arg1 resistance 255:264 the ever increasing resistance 235:264 the ever increasing resistance to antibiotics 235:279 In treatments of Helicobacter pylori infections, recrudescences were common because of an unfavorable bacterial eradication rate due to the ever increasing resistance to antibiotics. 24528746 1 44 theme rate 223:226 arg1 common 168:173 common 168:173 common 168:173 In treatments of Helicobacter pylori infections, recrudescences were common because of an unfavorable bacterial eradication rate due to the ever increasing resistance to antibiotics. 24528746 1 45 from treatments 102:111 arg1 common 168:173 common 168:173 common 168:173 In treatments of Helicobacter pylori infections, recrudescences were common because of an unfavorable bacterial eradication rate due to the ever increasing resistance to antibiotics. 24528746 0 46 theme Helicobacter 69:80 arg1 adhesion 89:96 Helicobacter pylori adhesion 69:96 Helicobacter pylori adhesion 69:96 Preparation and evaluation of polysaccharide sulfates for inhibiting Helicobacter pylori adhesion. 24528746 2 47 dep H. 389:390 arg1 pylori 392:397 H. pylori 389:397 H. pylori 389:397 In this study, we chose pectin, guar gum and chitosan to synthesize their sulfates to inhibit adhesions of H. pylori and thus enhance the eradication rate. 28456975 2 0 from N- 184:185 arg1 proteins 221:228 lysosomal proteins 211:228 lysosomal proteins of interest 211:240 The present protocol describes the method of analyzing N- and O-linked glycans in lysosomal proteins of interest. 28456975 6 1 theme Removing 576:583 arg1 oligosaccharides 585:600 Removing oligosaccharides 576:600 Removing oligosaccharides with glycosidases 576:618 Removing oligosaccharides with glycosidases increases the electrophoretic mobility of a protein. 28456975 8 2 attach present 952:958 arg1 protein 967:973 the protein 963:973 the protein 963:973 Therefore, the treatment of lysosomal proteins with specific glycosidases followed by a western blot analysis of a protein of interest provides a way to determine which types of glycans are present in the protein by comparing the gel mobility before and after treatment. 28456975 8 2 attach present 952:958 arg2 types 931:935 types 931:935 types of glycans 931:946 Therefore, the treatment of lysosomal proteins with specific glycosidases followed by a western blot analysis of a protein of interest provides a way to determine which types of glycans are present in the protein by comparing the gel mobility before and after treatment. 28456975 8 3 theme interest 888:895 arg1 protein 877:883 a protein 875:883 a protein of interest 875:895 Therefore, the treatment of lysosomal proteins with specific glycosidases followed by a western blot analysis of a protein of interest provides a way to determine which types of glycans are present in the protein by comparing the gel mobility before and after treatment. 28456975 7 4 dep size 714:717 arg1 the 710:712 the 710:712 the 710:712 This increase in mobility depends on the size and number of removed carbohydrate chains. 28456975 8 5 theme protein 877:883 arg1 analysis 863:870 a western blot analysis 848:870 a western blot analysis of a protein of interest 848:895 Therefore, the treatment of lysosomal proteins with specific glycosidases followed by a western blot analysis of a protein of interest provides a way to determine which types of glycans are present in the protein by comparing the gel mobility before and after treatment. 28456975 7 6 theme carbohydrate 741:752 arg1 chains 754:759 removed carbohydrate chains 733:759 removed carbohydrate chains 733:759 This increase in mobility depends on the size and number of removed carbohydrate chains. 28456975 3 7 gly deglycosylating 272:286 arg0 enzymes 288:294 deglycosylating enzymes 272:294 deglycosylating enzymes 272:294 The method is based on using deglycosylating enzymes, endoglycosidases, and exoglycosidases. 28456975 8 8 theme gel 992:994 arg1 mobility 996:1003 the gel mobility 988:1003 the gel mobility 988:1003 Therefore, the treatment of lysosomal proteins with specific glycosidases followed by a western blot analysis of a protein of interest provides a way to determine which types of glycans are present in the protein by comparing the gel mobility before and after treatment. 28456975 8 9 theme blot 858:861 arg1 analysis 863:870 a western blot analysis 848:870 a western blot analysis of a protein of interest 848:895 Therefore, the treatment of lysosomal proteins with specific glycosidases followed by a western blot analysis of a protein of interest provides a way to determine which types of glycans are present in the protein by comparing the gel mobility before and after treatment. 28456975 1 10 theme vast 67:70 arg1 majority 72:79 The vast majority 63:79 The vast majority of lysosomal proteins 63:101 The vast majority of lysosomal proteins are heavily glycosylated. 28456975 5 11 theme chains 528:533 arg1 types 494:498 Different types 484:498 Different types of carbohydrate residues or chains 484:533 Different types of carbohydrate residues or chains can be removed by specific glycosidases. 28456975 2 12 from glycans 200:206 arg1 proteins 221:228 lysosomal proteins 211:228 lysosomal proteins of interest 211:240 The present protocol describes the method of analyzing N- and O-linked glycans in lysosomal proteins of interest. 28456975 4 13 from bond 390:393 arg1 oligosaccharide 401:415 an oligosaccharide 398:415 an oligosaccharide 398:415 Endoglycosidases catalyze the cleavage of an internal bond in an oligosaccharide, while exoglycosidases remove terminal carbohydrates from glycans. 28456975 4 14 theme internal 381:388 arg1 bond 390:393 an internal bond 378:393 an internal bond in an oligosaccharide 378:415 Endoglycosidases catalyze the cleavage of an internal bond in an oligosaccharide, while exoglycosidases remove terminal carbohydrates from glycans. 28456975 8 15 from protein 967:973 arg1 present 952:958 present 952:958 present 952:958 Therefore, the treatment of lysosomal proteins with specific glycosidases followed by a western blot analysis of a protein of interest provides a way to determine which types of glycans are present in the protein by comparing the gel mobility before and after treatment. 28456975 6 16 theme protein 664:670 arg1 mobility 650:657 the electrophoretic mobility 630:657 the electrophoretic mobility of a protein 630:670 Removing oligosaccharides with glycosidases increases the electrophoretic mobility of a protein. 28456975 2 17 theme present 133:139 arg1 protocol 141:148 The present protocol 129:148 The present protocol 129:148 The present protocol describes the method of analyzing N- and O-linked glycans in lysosomal proteins of interest. 28456975 8 18 theme western 850:856 arg1 analysis 863:870 a western blot analysis 848:870 a western blot analysis of a protein of interest 848:895 Therefore, the treatment of lysosomal proteins with specific glycosidases followed by a western blot analysis of a protein of interest provides a way to determine which types of glycans are present in the protein by comparing the gel mobility before and after treatment. 28456975 1 19 theme lysosomal 84:92 arg1 proteins 94:101 lysosomal proteins 84:101 lysosomal proteins 84:101 The vast majority of lysosomal proteins are heavily glycosylated. 28456975 8 20 theme glycans 940:946 arg1 types 931:935 types 931:935 types of glycans 931:946 Therefore, the treatment of lysosomal proteins with specific glycosidases followed by a western blot analysis of a protein of interest provides a way to determine which types of glycans are present in the protein by comparing the gel mobility before and after treatment. 28456975 7 21 from increase 678:685 arg1 mobility 690:697 mobility 690:697 mobility 690:697 This increase in mobility depends on the size and number of removed carbohydrate chains. 28456975 1 22 gly glycosylated 115:126 arg1 majority 72:79 The vast majority 63:79 The vast majority of lysosomal proteins 63:101 The vast majority of lysosomal proteins are heavily glycosylated. 28456975 4 23 theme bond 390:393 arg1 cleavage 366:373 the cleavage 362:373 the cleavage of an internal bond in an oligosaccharide 362:415 Endoglycosidases catalyze the cleavage of an internal bond in an oligosaccharide, while exoglycosidases remove terminal carbohydrates from glycans. 28456975 1 24 theme proteins 94:101 arg1 majority 72:79 The vast majority 63:79 The vast majority of lysosomal proteins 63:101 The vast majority of lysosomal proteins are heavily glycosylated. 28456975 8 25 with treatment 777:785 arg1 glycosidases 823:834 specific glycosidases 814:834 specific glycosidases followed by a western blot analysis of a protein of interest 814:895 Therefore, the treatment of lysosomal proteins with specific glycosidases followed by a western blot analysis of a protein of interest provides a way to determine which types of glycans are present in the protein by comparing the gel mobility before and after treatment. 28456975 2 26 link O-linked 191:198 arg1 glycans 200:206 O-linked glycans 191:206 O-linked glycans 191:206 The present protocol describes the method of analyzing N- and O-linked glycans in lysosomal proteins of interest. 28456975 0 27 theme N- 12:13 arg1 Analysis 0:7 Analysis 0:7 Analysis of N- and O-Glycosylation of Lysosomal Glycoproteins. 0:61 Analysis of N- and O-Glycosylation of Lysosomal Glycoproteins. 28456975 3 28 theme deglycosylating 272:286 arg1 enzymes 288:294 deglycosylating enzymes 272:294 deglycosylating enzymes 272:294 The method is based on using deglycosylating enzymes, endoglycosidases, and exoglycosidases. 28456975 7 29 theme chains 754:759 arg1 number 723:728 number 723:728 number 723:728 This increase in mobility depends on the size and number of removed carbohydrate chains. 28456975 7 29 theme chains 754:759 arg1 size 714:717 size 714:717 size 714:717 This increase in mobility depends on the size and number of removed carbohydrate chains. 28456975 5 30 theme carbohydrate 503:514 arg1 residues 516:523 carbohydrate residues 503:523 carbohydrate residues 503:523 Different types of carbohydrate residues or chains can be removed by specific glycosidases. 28456975 6 31 theme electrophoretic 634:648 arg1 mobility 650:657 the electrophoretic mobility 630:657 the electrophoretic mobility of a protein 630:670 Removing oligosaccharides with glycosidases increases the electrophoretic mobility of a protein. 28456975 4 32 from glycans 475:481 arg1 carbohydrates 456:468 terminal carbohydrates 447:468 terminal carbohydrates from glycans 447:481 Endoglycosidases catalyze the cleavage of an internal bond in an oligosaccharide, while exoglycosidases remove terminal carbohydrates from glycans. 28456975 2 33 theme interest 233:240 arg1 proteins 221:228 lysosomal proteins 211:228 lysosomal proteins of interest 211:240 The present protocol describes the method of analyzing N- and O-linked glycans in lysosomal proteins of interest. 28456975 5 34 theme residues 516:523 arg1 types 494:498 Different types 484:498 Different types of carbohydrate residues or chains 484:533 Different types of carbohydrate residues or chains can be removed by specific glycosidases. 28456975 0 35 theme O-Glycosylation 19:33 arg1 Analysis 0:7 Analysis 0:7 Analysis of N- and O-Glycosylation of Lysosomal Glycoproteins. 0:61 Analysis of N- and O-Glycosylation of Lysosomal Glycoproteins. 28456975 8 36 theme lysosomal 790:798 arg1 proteins 800:807 lysosomal proteins 790:807 lysosomal proteins 790:807 Therefore, the treatment of lysosomal proteins with specific glycosidases followed by a western blot analysis of a protein of interest provides a way to determine which types of glycans are present in the protein by comparing the gel mobility before and after treatment. 28456975 7 37 theme removed 733:739 arg1 chains 754:759 removed carbohydrate chains 733:759 removed carbohydrate chains 733:759 This increase in mobility depends on the size and number of removed carbohydrate chains. 28456975 4 38 from cleavage 366:373 arg1 oligosaccharide 401:415 an oligosaccharide 398:415 an oligosaccharide 398:415 Endoglycosidases catalyze the cleavage of an internal bond in an oligosaccharide, while exoglycosidases remove terminal carbohydrates from glycans. 28456975 0 39 theme Glycoproteins 48:60 arg1 N- 12:13 N- 12:13 N- 12:13 Analysis of N- and O-Glycosylation of Lysosomal Glycoproteins. 28456975 0 39 theme Glycoproteins 48:60 arg1 O-Glycosylation 19:33 O-Glycosylation 19:33 O-Glycosylation 19:33 Analysis of N- and O-Glycosylation of Lysosomal Glycoproteins. 28456975 4 40 from oligosaccharide 401:415 arg1 cleavage 366:373 the cleavage 362:373 the cleavage of an internal bond in an oligosaccharide 362:415 Endoglycosidases catalyze the cleavage of an internal bond in an oligosaccharide, while exoglycosidases remove terminal carbohydrates from glycans. 28456975 0 41 theme Lysosomal 38:46 arg1 Glycoproteins 48:60 Lysosomal Glycoproteins 38:60 Lysosomal Glycoproteins 38:60 Analysis of N- and O-Glycosylation of Lysosomal Glycoproteins. 28456975 2 42 theme lysosomal 211:219 arg1 proteins 221:228 lysosomal proteins 211:228 lysosomal proteins of interest 211:240 The present protocol describes the method of analyzing N- and O-linked glycans in lysosomal proteins of interest. 28456975 8 43 theme proteins 800:807 arg1 treatment 777:785 the treatment 773:785 the treatment of lysosomal proteins with specific glycosidases followed by a western blot analysis of a protein of interest 773:895 Therefore, the treatment of lysosomal proteins with specific glycosidases followed by a western blot analysis of a protein of interest provides a way to determine which types of glycans are present in the protein by comparing the gel mobility before and after treatment. 28456975 8 44 from present 952:958 arg1 protein 967:973 the protein 963:973 the protein 963:973 Therefore, the treatment of lysosomal proteins with specific glycosidases followed by a western blot analysis of a protein of interest provides a way to determine which types of glycans are present in the protein by comparing the gel mobility before and after treatment. 28456975 0 45 gly O-Glycosylation 19:33 arg1 Glycoproteins 48:60 Lysosomal Glycoproteins 38:60 Lysosomal Glycoproteins 38:60 Analysis of N- and O-Glycosylation of Lysosomal Glycoproteins. 28456975 6 46 with oligosaccharides 585:600 arg1 glycosidases 607:618 glycosidases 607:618 glycosidases 607:618 Removing oligosaccharides with glycosidases increases the electrophoretic mobility of a protein. 28456975 2 47 theme O-linked 191:198 arg1 glycans 200:206 O-linked glycans 191:206 O-linked glycans 191:206 The present protocol describes the method of analyzing N- and O-linked glycans in lysosomal proteins of interest. 28456975 8 48 theme specific 814:821 arg1 glycosidases 823:834 specific glycosidases 814:834 specific glycosidases followed by a western blot analysis of a protein of interest 814:895 Therefore, the treatment of lysosomal proteins with specific glycosidases followed by a western blot analysis of a protein of interest provides a way to determine which types of glycans are present in the protein by comparing the gel mobility before and after treatment. 28456975 4 49 theme terminal 447:454 arg1 carbohydrates 456:468 terminal carbohydrates 447:468 terminal carbohydrates from glycans 447:481 Endoglycosidases catalyze the cleavage of an internal bond in an oligosaccharide, while exoglycosidases remove terminal carbohydrates from glycans. 28456975 8 50 located present 952:958 arg1 protein 967:973 the protein 963:973 the protein 963:973 Therefore, the treatment of lysosomal proteins with specific glycosidases followed by a western blot analysis of a protein of interest provides a way to determine which types of glycans are present in the protein by comparing the gel mobility before and after treatment. 28456975 8 50 located present 952:958 arg2 types 931:935 types 931:935 types of glycans 931:946 Therefore, the treatment of lysosomal proteins with specific glycosidases followed by a western blot analysis of a protein of interest provides a way to determine which types of glycans are present in the protein by comparing the gel mobility before and after treatment. 28456975 5 51 theme Different 484:492 arg1 types 494:498 Different types 484:498 Different types of carbohydrate residues or chains 484:533 Different types of carbohydrate residues or chains can be removed by specific glycosidases. 28456975 5 52 theme specific 553:560 arg1 glycosidases 562:573 specific glycosidases 553:573 specific glycosidases 553:573 Different types of carbohydrate residues or chains can be removed by specific glycosidases. 27139196 3 0 link O-linked 428:435 arg1 sialosides 437:446 O-linked sialosides 428:446 O-linked sialosides toward influenza virus neuraminidase and intact virus 428:500 We evaluated the binding affinity of multiple lectins and compared the stability of these sialosides with O-linked sialosides toward influenza virus neuraminidase and intact virus. 27139196 1 1 theme sialosides 147:156 arg1 synthesis 89:97 the synthesis 85:97 the synthesis of influenza virus neuraminidase (NA) resistant sialosides that include different glycoside linkages (C-, S-, and triazole) 85:221 We report the synthesis of influenza virus neuraminidase (NA) resistant sialosides that include different glycoside linkages (C-, S-, and triazole). 27139196 4 2 theme different 567:575 arg1 strains 577:583 eight different strains 561:583 eight different strains of influenza virus at ambient temperature 561:625 We demonstrated the ability of these molecules to capture eight different strains of influenza virus at ambient temperature without the addition of NA inhibitors. 27139196 2 3 theme glass 269:273 arg1 slides 275:280 glass slides 269:280 glass slides 269:280 These unnatural sialosides were printed onto glass slides to generate a small focused microarray. 27139196 5 4 used used 846:849 arg2 pattern 810:816 a specific "fingerprint" binding pattern 777:816 a specific "fingerprint" binding pattern 777:816 The glycans capture extremely low, clinically relevant concentrations of viruses and each strain gives rise to a specific "fingerprint" binding pattern, which could potentially be used in rapid diagnostic tests. 27139196 4 5 theme influenza 588:596 arg1 virus 598:602 influenza virus 588:602 influenza virus 588:602 We demonstrated the ability of these molecules to capture eight different strains of influenza virus at ambient temperature without the addition of NA inhibitors. 27139196 3 6 theme binding 339:345 arg1 affinity 347:354 the binding affinity 335:354 the binding affinity of multiple lectins 335:374 We evaluated the binding affinity of multiple lectins and compared the stability of these sialosides with O-linked sialosides toward influenza virus neuraminidase and intact virus. 27139196 5 7 theme " 800:800 arg1 pattern 810:816 a specific "fingerprint" binding pattern 777:816 a specific "fingerprint" binding pattern 777:816 The glycans capture extremely low, clinically relevant concentrations of viruses and each strain gives rise to a specific "fingerprint" binding pattern, which could potentially be used in rapid diagnostic tests. 27139196 5 8 theme rapid 854:858 arg1 tests 871:875 rapid diagnostic tests 854:875 rapid diagnostic tests 854:875 The glycans capture extremely low, clinically relevant concentrations of viruses and each strain gives rise to a specific "fingerprint" binding pattern, which could potentially be used in rapid diagnostic tests. 27139196 3 9 theme sialosides 412:421 arg1 stability 393:401 the stability 389:401 the stability of these sialosides 389:421 We evaluated the binding affinity of multiple lectins and compared the stability of these sialosides with O-linked sialosides toward influenza virus neuraminidase and intact virus. 27139196 5 10 dep low 696:698 arg1 relevant 712:719 relevant 712:719 relevant 712:719 The glycans capture extremely low, clinically relevant concentrations of viruses and each strain gives rise to a specific "fingerprint" binding pattern, which could potentially be used in rapid diagnostic tests. 27139196 3 11 theme lectins 368:374 arg1 affinity 347:354 the binding affinity 335:354 the binding affinity of multiple lectins 335:374 We evaluated the binding affinity of multiple lectins and compared the stability of these sialosides with O-linked sialosides toward influenza virus neuraminidase and intact virus. 27139196 1 12 theme different 171:179 arg1 triazole 213:220 triazole 213:220 triazole 213:220 We report the synthesis of influenza virus neuraminidase (NA) resistant sialosides that include different glycoside linkages (C-, S-, and triazole). 27139196 1 12 theme different 171:179 arg1 C- 201:202 C- 201:202 C- 201:202 We report the synthesis of influenza virus neuraminidase (NA) resistant sialosides that include different glycoside linkages (C-, S-, and triazole). 27139196 1 12 theme different 171:179 arg1 linkages 191:198 different glycoside linkages 171:198 different glycoside linkages (C-, S-, and triazole) 171:221 We report the synthesis of influenza virus neuraminidase (NA) resistant sialosides that include different glycoside linkages (C-, S-, and triazole). 27139196 1 12 theme different 171:179 arg1 S- 205:206 S- 205:206 S- 205:206 We report the synthesis of influenza virus neuraminidase (NA) resistant sialosides that include different glycoside linkages (C-, S-, and triazole). 27139196 0 13 theme Resistant 14:22 arg1 Sialosides 24:33 Neuraminidase Resistant Sialosides 0:33 Neuraminidase Resistant Sialosides for the Detection of Influenza Viruses. 0:73 Neuraminidase Resistant Sialosides for the Detection of Influenza Viruses. 27139196 4 14 theme NA 651:652 arg1 inhibitors 654:663 NA inhibitors 651:663 NA inhibitors 651:663 We demonstrated the ability of these molecules to capture eight different strains of influenza virus at ambient temperature without the addition of NA inhibitors. 27139196 1 15 theme glycoside 181:189 arg1 triazole 213:220 triazole 213:220 triazole 213:220 We report the synthesis of influenza virus neuraminidase (NA) resistant sialosides that include different glycoside linkages (C-, S-, and triazole). 27139196 1 15 theme glycoside 181:189 arg1 C- 201:202 C- 201:202 C- 201:202 We report the synthesis of influenza virus neuraminidase (NA) resistant sialosides that include different glycoside linkages (C-, S-, and triazole). 27139196 1 15 theme glycoside 181:189 arg1 linkages 191:198 different glycoside linkages 171:198 different glycoside linkages (C-, S-, and triazole) 171:221 We report the synthesis of influenza virus neuraminidase (NA) resistant sialosides that include different glycoside linkages (C-, S-, and triazole). 27139196 1 15 theme glycoside 181:189 arg1 S- 205:206 S- 205:206 S- 205:206 We report the synthesis of influenza virus neuraminidase (NA) resistant sialosides that include different glycoside linkages (C-, S-, and triazole). 27139196 0 16 theme Neuraminidase 0:12 arg1 Sialosides 24:33 Neuraminidase Resistant Sialosides 0:33 Neuraminidase Resistant Sialosides for the Detection of Influenza Viruses. 0:73 Neuraminidase Resistant Sialosides for the Detection of Influenza Viruses. 27139196 5 17 theme binding 802:808 arg1 pattern 810:816 a specific "fingerprint" binding pattern 777:816 a specific "fingerprint" binding pattern 777:816 The glycans capture extremely low, clinically relevant concentrations of viruses and each strain gives rise to a specific "fingerprint" binding pattern, which could potentially be used in rapid diagnostic tests. 27139196 5 18 theme diagnostic 860:869 arg1 tests 871:875 rapid diagnostic tests 854:875 rapid diagnostic tests 854:875 The glycans capture extremely low, clinically relevant concentrations of viruses and each strain gives rise to a specific "fingerprint" binding pattern, which could potentially be used in rapid diagnostic tests. 27139196 4 19 theme molecules 540:548 arg1 ability 523:529 the ability 519:529 the ability of these molecules to capture eight different strains of influenza virus at ambient temperature without the addition of NA inhibitors 519:663 We demonstrated the ability of these molecules to capture eight different strains of influenza virus at ambient temperature without the addition of NA inhibitors. 27139196 1 20 theme influenza 102:110 arg1 NA 133:134 NA 133:134 NA 133:134 We report the synthesis of influenza virus neuraminidase (NA) resistant sialosides that include different glycoside linkages (C-, S-, and triazole). 27139196 1 20 theme influenza 102:110 arg1 neuraminidase 118:130 influenza virus neuraminidase 102:130 influenza virus neuraminidase (NA) resistant sialosides that include different glycoside linkages (C-, S-, and triazole) 102:221 We report the synthesis of influenza virus neuraminidase (NA) resistant sialosides that include different glycoside linkages (C-, S-, and triazole). 27139196 3 21 theme influenza 455:463 arg1 virus 465:469 influenza virus neuraminidase and intact virus 455:500 virus 465:469 We evaluated the binding affinity of multiple lectins and compared the stability of these sialosides with O-linked sialosides toward influenza virus neuraminidase and intact virus. 27139196 3 22 theme intact 489:494 arg1 virus 496:500 intact virus 489:500 intact virus 489:500 We evaluated the binding affinity of multiple lectins and compared the stability of these sialosides with O-linked sialosides toward influenza virus neuraminidase and intact virus. 27139196 3 23 theme O-linked 428:435 arg1 sialosides 437:446 O-linked sialosides 428:446 O-linked sialosides toward influenza virus neuraminidase and intact virus 428:500 We evaluated the binding affinity of multiple lectins and compared the stability of these sialosides with O-linked sialosides toward influenza virus neuraminidase and intact virus. 27139196 4 24 theme inhibitors 654:663 arg1 addition 639:646 the addition 635:646 the addition of NA inhibitors 635:663 We demonstrated the ability of these molecules to capture eight different strains of influenza virus at ambient temperature without the addition of NA inhibitors. 27139196 5 25 theme specific 779:786 arg1 pattern 810:816 a specific "fingerprint" binding pattern 777:816 a specific "fingerprint" binding pattern 777:816 The glycans capture extremely low, clinically relevant concentrations of viruses and each strain gives rise to a specific "fingerprint" binding pattern, which could potentially be used in rapid diagnostic tests. 27139196 5 26 theme viruses 739:745 arg1 concentrations 721:734 extremely low, clinically relevant concentrations 686:734 extremely low, clinically relevant concentrations of viruses 686:745 The glycans capture extremely low, clinically relevant concentrations of viruses and each strain gives rise to a specific "fingerprint" binding pattern, which could potentially be used in rapid diagnostic tests. 27139196 1 27 dep linkages 191:198 arg1 triazole 213:220 triazole 213:220 triazole 213:220 We report the synthesis of influenza virus neuraminidase (NA) resistant sialosides that include different glycoside linkages (C-, S-, and triazole). 27139196 1 27 dep linkages 191:198 arg1 C- 201:202 C- 201:202 C- 201:202 We report the synthesis of influenza virus neuraminidase (NA) resistant sialosides that include different glycoside linkages (C-, S-, and triazole). 27139196 1 27 dep linkages 191:198 arg1 linkages 191:198 different glycoside linkages 171:198 different glycoside linkages (C-, S-, and triazole) 171:221 We report the synthesis of influenza virus neuraminidase (NA) resistant sialosides that include different glycoside linkages (C-, S-, and triazole). 27139196 1 27 dep linkages 191:198 arg1 S- 205:206 S- 205:206 S- 205:206 We report the synthesis of influenza virus neuraminidase (NA) resistant sialosides that include different glycoside linkages (C-, S-, and triazole). 27139196 0 28 theme Influenza 56:64 arg1 Viruses 66:72 Influenza Viruses 56:72 Influenza Viruses 56:72 Neuraminidase Resistant Sialosides for the Detection of Influenza Viruses. 27139196 1 29 theme virus 112:116 arg1 NA 133:134 NA 133:134 NA 133:134 We report the synthesis of influenza virus neuraminidase (NA) resistant sialosides that include different glycoside linkages (C-, S-, and triazole). 27139196 1 29 theme virus 112:116 arg1 neuraminidase 118:130 influenza virus neuraminidase 102:130 influenza virus neuraminidase (NA) resistant sialosides that include different glycoside linkages (C-, S-, and triazole) 102:221 We report the synthesis of influenza virus neuraminidase (NA) resistant sialosides that include different glycoside linkages (C-, S-, and triazole). 27139196 5 30 theme fingerprint 789:799 arg1 pattern 810:816 a specific "fingerprint" binding pattern 777:816 a specific "fingerprint" binding pattern 777:816 The glycans capture extremely low, clinically relevant concentrations of viruses and each strain gives rise to a specific "fingerprint" binding pattern, which could potentially be used in rapid diagnostic tests. 27139196 3 31 dep virus 465:469 arg1 neuraminidase 471:483 neuraminidase 471:483 neuraminidase 471:483 We evaluated the binding affinity of multiple lectins and compared the stability of these sialosides with O-linked sialosides toward influenza virus neuraminidase and intact virus. 27139196 1 32 theme neuraminidase 118:130 arg1 sialosides 147:156 influenza virus neuraminidase (NA) resistant sialosides 102:156 influenza virus neuraminidase (NA) resistant sialosides that include different glycoside linkages (C-, S-, and triazole) 102:221 We report the synthesis of influenza virus neuraminidase (NA) resistant sialosides that include different glycoside linkages (C-, S-, and triazole). 27139196 2 33 theme focused 302:308 arg1 microarray 310:319 a small focused microarray 294:319 a small focused microarray 294:319 These unnatural sialosides were printed onto glass slides to generate a small focused microarray. 27139196 5 34 theme low 696:698 arg1 concentrations 721:734 extremely low, clinically relevant concentrations 686:734 extremely low, clinically relevant concentrations of viruses 686:745 The glycans capture extremely low, clinically relevant concentrations of viruses and each strain gives rise to a specific "fingerprint" binding pattern, which could potentially be used in rapid diagnostic tests. 27139196 2 35 theme unnatural 230:238 arg1 sialosides 240:249 These unnatural sialosides 224:249 These unnatural sialosides 224:249 These unnatural sialosides were printed onto glass slides to generate a small focused microarray. 27139196 2 36 theme small 296:300 arg1 microarray 310:319 a small focused microarray 294:319 a small focused microarray 294:319 These unnatural sialosides were printed onto glass slides to generate a small focused microarray. 27139196 4 37 theme virus 598:602 arg1 strains 577:583 eight different strains 561:583 eight different strains of influenza virus at ambient temperature 561:625 We demonstrated the ability of these molecules to capture eight different strains of influenza virus at ambient temperature without the addition of NA inhibitors. 27139196 4 38 from temperature 615:625 arg1 strains 577:583 eight different strains 561:583 eight different strains of influenza virus at ambient temperature 561:625 We demonstrated the ability of these molecules to capture eight different strains of influenza virus at ambient temperature without the addition of NA inhibitors. 27139196 3 39 theme multiple 359:366 arg1 lectins 368:374 multiple lectins 359:374 multiple lectins 359:374 We evaluated the binding affinity of multiple lectins and compared the stability of these sialosides with O-linked sialosides toward influenza virus neuraminidase and intact virus. 27139196 0 40 theme Viruses 66:72 arg1 Detection 43:51 the Detection 39:51 the Detection of Influenza Viruses 39:72 Neuraminidase Resistant Sialosides for the Detection of Influenza Viruses. 27139196 1 41 theme resistant 137:145 arg1 sialosides 147:156 influenza virus neuraminidase (NA) resistant sialosides 102:156 influenza virus neuraminidase (NA) resistant sialosides that include different glycoside linkages (C-, S-, and triazole) 102:221 We report the synthesis of influenza virus neuraminidase (NA) resistant sialosides that include different glycoside linkages (C-, S-, and triazole). 27139196 4 42 theme ambient 607:613 arg1 temperature 615:625 ambient temperature 607:625 ambient temperature 607:625 We demonstrated the ability of these molecules to capture eight different strains of influenza virus at ambient temperature without the addition of NA inhibitors. 26838809 5 0 theme 3-N-linked 535:544 arg1 auxiliary 565:573 The 3-N-linked 4-mercaptobutyrate auxiliary 531:573 The 3-N-linked 4-mercaptobutyrate auxiliary 531:573 The 3-N-linked 4-mercaptobutyrate auxiliary is readily synthesized in a single step and enables introduction on solid phase by means of reductive amination. 26838809 1 1 theme S-N 123:125 arg1 shift 132:136 a S-N acyl shift 121:136 a S-N acyl shift 121:136 Native chemical ligation (NCL) proceeds via a S-N acyl shift and, therefore, requires N-terminal cysteine. 26838809 2 2 used used 216:219 arg2 -auxiliaries 188:199 N(α)-auxiliaries 184:199 N(α)-auxiliaries 184:199 N(α)-auxiliaries have long been used to enable NCL beyond cysteine. 26838809 5 3 theme reductive 667:675 arg1 amination 677:685 reductive amination 667:685 reductive amination 667:685 The 3-N-linked 4-mercaptobutyrate auxiliary is readily synthesized in a single step and enables introduction on solid phase by means of reductive amination. 26838809 5 4 theme 4-mercaptobutyrate 546:563 arg1 auxiliary 565:573 The 3-N-linked 4-mercaptobutyrate auxiliary 531:573 The 3-N-linked 4-mercaptobutyrate auxiliary 531:573 The 3-N-linked 4-mercaptobutyrate auxiliary is readily synthesized in a single step and enables introduction on solid phase by means of reductive amination. 26838809 6 5 theme auxiliary 714:722 arg1 usefulness 692:701 The usefulness 688:701 The usefulness of the new auxiliary 688:722 The usefulness of the new auxiliary was demonstrated in the synthesis of the anti-microbial C-terminal domain of Dermicidine-1L. 26838809 1 6 theme acyl 127:130 arg1 shift 132:136 a S-N acyl shift 121:136 a S-N acyl shift 121:136 Native chemical ligation (NCL) proceeds via a S-N acyl shift and, therefore, requires N-terminal cysteine. 26838809 4 7 theme -auxiliary 461:470 arg1 class 448:452 a new class 442:452 a new class of N(α)-auxiliary which is designed for removal under mild basic conditions 442:528 Herein, we introduce a new class of N(α)-auxiliary which is designed for removal under mild basic conditions. 26838809 3 8 theme S-N 286:288 arg1 shift 295:299 the S-N acyl shift 282:299 the S-N acyl shift 282:299 However, the reversibility of the S-N acyl shift under the acidic conditions used to remove the commonly applied N-benzyl auxiliaries limits the scope of this reaction. 26838809 6 9 theme new 710:712 arg1 auxiliary 714:722 the new auxiliary 706:722 the new auxiliary 706:722 The usefulness of the new auxiliary was demonstrated in the synthesis of the anti-microbial C-terminal domain of Dermicidine-1L. 26838809 3 10 theme acyl 290:293 arg1 shift 295:299 the S-N acyl shift 282:299 the S-N acyl shift 282:299 However, the reversibility of the S-N acyl shift under the acidic conditions used to remove the commonly applied N-benzyl auxiliaries limits the scope of this reaction. 26838809 6 11 theme Dermicidine-1L 801:814 arg1 Dermicidine-1L 801:814 Dermicidine-1L 801:814 Dermicidine-1L 801:814 The usefulness of the new auxiliary was demonstrated in the synthesis of the anti-microbial C-terminal domain of Dermicidine-1L. 26838809 6 11 theme Dermicidine-1L 801:814 arg1 domain 791:796 the anti-microbial C-terminal domain 761:796 the anti-microbial C-terminal domain of Dermicidine-1L 761:814 The usefulness of the new auxiliary was demonstrated in the synthesis of the anti-microbial C-terminal domain of Dermicidine-1L. 26838809 1 12 dep proceeds 108:115 arg1 requires 154:161 requires 154:161 requires N-terminal cysteine 154:181 Native chemical ligation (NCL) proceeds via a S-N acyl shift and, therefore, requires N-terminal cysteine. 26838809 5 13 theme solid 643:647 arg1 phase 649:653 solid phase 643:653 solid phase 643:653 The 3-N-linked 4-mercaptobutyrate auxiliary is readily synthesized in a single step and enables introduction on solid phase by means of reductive amination. 26838809 3 14 theme applied 357:363 arg1 auxiliaries 374:384 the commonly applied N-benzyl auxiliaries 344:384 the commonly applied N-benzyl auxiliaries 344:384 However, the reversibility of the S-N acyl shift under the acidic conditions used to remove the commonly applied N-benzyl auxiliaries limits the scope of this reaction. 26838809 0 15 from base-labile 30:40 arg1 ligation 16:23 Native chemical ligation 0:23 Native chemical ligation at a base-labile 0:40 Native chemical ligation at a base-labile 4-mercaptobutyrate N(α)-auxiliary. 26838809 0 16 theme Native 0:5 arg1 ligation 16:23 Native chemical ligation 0:23 Native chemical ligation at a base-labile 0:40 Native chemical ligation at a base-labile 4-mercaptobutyrate N(α)-auxiliary. 26838809 3 17 theme N-benzyl 365:372 arg1 auxiliaries 374:384 the commonly applied N-benzyl auxiliaries 344:384 the commonly applied N-benzyl auxiliaries 344:384 However, the reversibility of the S-N acyl shift under the acidic conditions used to remove the commonly applied N-benzyl auxiliaries limits the scope of this reaction. 26838809 0 18 theme chemical 7:14 arg1 ligation 16:23 Native chemical ligation 0:23 Native chemical ligation at a base-labile 0:40 Native chemical ligation at a base-labile 4-mercaptobutyrate N(α)-auxiliary. 26838809 6 19 theme C-terminal 780:789 arg1 Dermicidine-1L 801:814 Dermicidine-1L 801:814 Dermicidine-1L 801:814 The usefulness of the new auxiliary was demonstrated in the synthesis of the anti-microbial C-terminal domain of Dermicidine-1L. 26838809 6 19 theme C-terminal 780:789 arg1 domain 791:796 the anti-microbial C-terminal domain 761:796 the anti-microbial C-terminal domain of Dermicidine-1L 761:814 The usefulness of the new auxiliary was demonstrated in the synthesis of the anti-microbial C-terminal domain of Dermicidine-1L. 26838809 3 20 theme acidic 311:316 arg1 conditions 318:327 the acidic conditions 307:327 the acidic conditions used to remove the commonly applied N-benzyl auxiliaries 307:384 However, the reversibility of the S-N acyl shift under the acidic conditions used to remove the commonly applied N-benzyl auxiliaries limits the scope of this reaction. 26838809 1 21 theme Native 77:82 arg1 NCL 103:105 NCL 103:105 NCL 103:105 Native chemical ligation (NCL) proceeds via a S-N acyl shift and, therefore, requires N-terminal cysteine. 26838809 1 21 theme Native 77:82 arg1 ligation 93:100 Native chemical ligation 77:100 Native chemical ligation (NCL) 77:106 Native chemical ligation (NCL) proceeds via a S-N acyl shift and, therefore, requires N-terminal cysteine. 26838809 3 22 theme shift 295:299 arg1 reversibility 265:277 the reversibility 261:277 the reversibility of the S-N acyl shift under the acidic conditions used to remove the commonly applied N-benzyl auxiliaries 261:384 However, the reversibility of the S-N acyl shift under the acidic conditions used to remove the commonly applied N-benzyl auxiliaries limits the scope of this reaction. 26838809 4 23 theme N 457:457 arg1 -auxiliary 461:470 N(α)-auxiliary 457:470 N(α)-auxiliary which is designed for removal under mild basic conditions 457:528 Herein, we introduce a new class of N(α)-auxiliary which is designed for removal under mild basic conditions. 26838809 5 24 theme single 603:608 arg1 step 610:613 a single step 601:613 a single step 601:613 The 3-N-linked 4-mercaptobutyrate auxiliary is readily synthesized in a single step and enables introduction on solid phase by means of reductive amination. 26838809 1 25 theme chemical 84:91 arg1 NCL 103:105 NCL 103:105 NCL 103:105 Native chemical ligation (NCL) proceeds via a S-N acyl shift and, therefore, requires N-terminal cysteine. 26838809 1 25 theme chemical 84:91 arg1 ligation 93:100 Native chemical ligation 77:100 Native chemical ligation (NCL) 77:106 Native chemical ligation (NCL) proceeds via a S-N acyl shift and, therefore, requires N-terminal cysteine. 26838809 6 26 theme anti-microbial 765:778 arg1 Dermicidine-1L 801:814 Dermicidine-1L 801:814 Dermicidine-1L 801:814 The usefulness of the new auxiliary was demonstrated in the synthesis of the anti-microbial C-terminal domain of Dermicidine-1L. 26838809 6 26 theme anti-microbial 765:778 arg1 domain 791:796 the anti-microbial C-terminal domain 761:796 the anti-microbial C-terminal domain of Dermicidine-1L 761:814 The usefulness of the new auxiliary was demonstrated in the synthesis of the anti-microbial C-terminal domain of Dermicidine-1L. 26838809 4 27 theme basic 513:517 arg1 conditions 519:528 mild basic conditions 508:528 mild basic conditions 508:528 Herein, we introduce a new class of N(α)-auxiliary which is designed for removal under mild basic conditions. 26838809 4 28 theme α 459:459 arg1 -auxiliary 461:470 N(α)-auxiliary 457:470 N(α)-auxiliary which is designed for removal under mild basic conditions 457:528 Herein, we introduce a new class of N(α)-auxiliary which is designed for removal under mild basic conditions. 26838809 5 29 link 3-N-linked 535:544 arg1 auxiliary 565:573 The 3-N-linked 4-mercaptobutyrate auxiliary 531:573 The 3-N-linked 4-mercaptobutyrate auxiliary 531:573 The 3-N-linked 4-mercaptobutyrate auxiliary is readily synthesized in a single step and enables introduction on solid phase by means of reductive amination. 26838809 1 30 theme N-terminal 163:172 arg1 cysteine 174:181 N-terminal cysteine 163:181 N-terminal cysteine 163:181 Native chemical ligation (NCL) proceeds via a S-N acyl shift and, therefore, requires N-terminal cysteine. 26838809 4 31 theme new 444:446 arg1 class 448:452 a new class 442:452 a new class of N(α)-auxiliary which is designed for removal under mild basic conditions 442:528 Herein, we introduce a new class of N(α)-auxiliary which is designed for removal under mild basic conditions. 26838809 5 32 from introduction 627:638 arg1 phase 649:653 solid phase 643:653 solid phase 643:653 The 3-N-linked 4-mercaptobutyrate auxiliary is readily synthesized in a single step and enables introduction on solid phase by means of reductive amination. 26838809 2 33 theme N 184:184 arg1 -auxiliaries 188:199 N(α)-auxiliaries 184:199 N(α)-auxiliaries 184:199 N(α)-auxiliaries have long been used to enable NCL beyond cysteine. 26838809 6 34 theme domain 791:796 arg1 synthesis 748:756 the synthesis 744:756 the synthesis of the anti-microbial C-terminal domain of Dermicidine-1L 744:814 The usefulness of the new auxiliary was demonstrated in the synthesis of the anti-microbial C-terminal domain of Dermicidine-1L. 26838809 3 35 theme reaction 411:418 arg1 scope 397:401 the scope 393:401 the scope of this reaction 393:418 However, the reversibility of the S-N acyl shift under the acidic conditions used to remove the commonly applied N-benzyl auxiliaries limits the scope of this reaction. 26838809 4 36 theme mild 508:511 arg1 conditions 519:528 mild basic conditions 508:528 mild basic conditions 508:528 Herein, we introduce a new class of N(α)-auxiliary which is designed for removal under mild basic conditions. 26082212 4 0 theme forward 637:643 arg1 engineering 645:655 forward engineering 637:655 forward engineering 637:655 DNA sequenced targets demonstrating increased levels of glycan production were selected for forward engineering, protein overexpression, and absolute quantification of glycoproteins. 26082212 4 1 theme sequenced 549:557 arg1 targets 559:565 DNA sequenced targets 545:565 DNA sequenced targets demonstrating increased levels of glycan production 545:617 DNA sequenced targets demonstrating increased levels of glycan production were selected for forward engineering, protein overexpression, and absolute quantification of glycoproteins. 26082212 2 2 theme glycosylation 330:342 arg1 efficiency 344:353 the N-linked glycosylation efficiency 317:353 the N-linked glycosylation efficiency of Escherichia coli 317:373 This methodology has been successfully applied towards enhancing the N-linked glycosylation efficiency of Escherichia coli. 26082212 4 3 theme absolute 686:693 arg1 quantification 695:708 absolute quantification 686:708 absolute quantification of glycoproteins 686:725 DNA sequenced targets demonstrating increased levels of glycan production were selected for forward engineering, protein overexpression, and absolute quantification of glycoproteins. 26082212 0 4 from Production 56:65 arg1 coli 82:85 Escherichia coli 70:85 Escherichia coli 70:85 Inverse Metabolic Engineering for Enhanced Glycoprotein Production in Escherichia coli. 26082212 3 5 theme high-throughput 485:499 arg1 screening 534:542 high-throughput semiquantitative glycan specific screening 485:542 high-throughput semiquantitative glycan specific screening 485:542 Here, we describe the generation of differentially sized libraries from the E. coli W3110 genome followed by high-throughput semiquantitative glycan specific screening. 26082212 1 6 theme genetic 168:174 arg1 elements 176:183 the genetic elements 164:183 the genetic elements responsible for the desired phenotype of a chosen target organism 164:249 Inverse metabolic engineering (IME) provides a strategy to rapidly identify the genetic elements responsible for the desired phenotype of a chosen target organism. 26082212 0 7 theme Glycoprotein 43:54 arg1 Production 56:65 Enhanced Glycoprotein Production 34:65 Enhanced Glycoprotein Production in Escherichia coli 34:85 Inverse Metabolic Engineering for Enhanced Glycoprotein Production in Escherichia coli. 26082212 1 8 theme Inverse 88:94 arg1 engineering 106:116 Inverse metabolic engineering 88:116 Inverse metabolic engineering (IME) 88:122 Inverse metabolic engineering (IME) provides a strategy to rapidly identify the genetic elements responsible for the desired phenotype of a chosen target organism. 26082212 1 8 theme Inverse 88:94 arg1 IME 119:121 IME 119:121 IME 119:121 Inverse metabolic engineering (IME) provides a strategy to rapidly identify the genetic elements responsible for the desired phenotype of a chosen target organism. 26082212 3 9 theme specific 525:532 arg1 screening 534:542 high-throughput semiquantitative glycan specific screening 485:542 high-throughput semiquantitative glycan specific screening 485:542 Here, we describe the generation of differentially sized libraries from the E. coli W3110 genome followed by high-throughput semiquantitative glycan specific screening. 26082212 3 10 theme W3110 460:464 arg1 genome 466:471 the E. coli W3110 genome 448:471 the E. coli W3110 genome followed by high-throughput semiquantitative glycan specific screening 448:542 Here, we describe the generation of differentially sized libraries from the E. coli W3110 genome followed by high-throughput semiquantitative glycan specific screening. 26082212 0 11 theme Metabolic 8:16 arg1 Engineering 18:28 Inverse Metabolic Engineering 0:28 Inverse Metabolic Engineering for Enhanced Glycoprotein Production in Escherichia coli 0:85 Inverse Metabolic Engineering for Enhanced Glycoprotein Production in Escherichia coli. 26082212 1 12 theme metabolic 96:104 arg1 engineering 106:116 Inverse metabolic engineering 88:116 Inverse metabolic engineering (IME) 88:122 Inverse metabolic engineering (IME) provides a strategy to rapidly identify the genetic elements responsible for the desired phenotype of a chosen target organism. 26082212 1 12 theme metabolic 96:104 arg1 IME 119:121 IME 119:121 IME 119:121 Inverse metabolic engineering (IME) provides a strategy to rapidly identify the genetic elements responsible for the desired phenotype of a chosen target organism. 26082212 1 13 theme responsible 185:195 arg1 elements 176:183 the genetic elements 164:183 the genetic elements responsible for the desired phenotype of a chosen target organism 164:249 Inverse metabolic engineering (IME) provides a strategy to rapidly identify the genetic elements responsible for the desired phenotype of a chosen target organism. 26082212 0 14 theme Inverse 0:6 arg1 Engineering 18:28 Inverse Metabolic Engineering 0:28 Inverse Metabolic Engineering for Enhanced Glycoprotein Production in Escherichia coli 0:85 Inverse Metabolic Engineering for Enhanced Glycoprotein Production in Escherichia coli. 26082212 4 15 theme production 608:617 arg1 levels 591:596 increased levels 581:596 increased levels of glycan production 581:617 DNA sequenced targets demonstrating increased levels of glycan production were selected for forward engineering, protein overexpression, and absolute quantification of glycoproteins. 26082212 4 16 gly glycoproteins 713:725 arg1 glycoproteins 713:725 glycoproteins 713:725 glycoproteins 713:725 DNA sequenced targets demonstrating increased levels of glycan production were selected for forward engineering, protein overexpression, and absolute quantification of glycoproteins. 26082212 2 17 theme N-linked 321:328 arg1 efficiency 344:353 the N-linked glycosylation efficiency 317:353 the N-linked glycosylation efficiency of Escherichia coli 317:373 This methodology has been successfully applied towards enhancing the N-linked glycosylation efficiency of Escherichia coli. 26082212 3 18 theme E. 452:453 arg1 genome 466:471 the E. coli W3110 genome 448:471 the E. coli W3110 genome followed by high-throughput semiquantitative glycan specific screening 448:542 Here, we describe the generation of differentially sized libraries from the E. coli W3110 genome followed by high-throughput semiquantitative glycan specific screening. 26082212 4 19 theme protein 658:664 arg1 overexpression 666:679 protein overexpression 658:679 protein overexpression 658:679 DNA sequenced targets demonstrating increased levels of glycan production were selected for forward engineering, protein overexpression, and absolute quantification of glycoproteins. 26082212 4 20 theme glycan 601:606 arg1 production 608:617 glycan production 601:617 glycan production 601:617 DNA sequenced targets demonstrating increased levels of glycan production were selected for forward engineering, protein overexpression, and absolute quantification of glycoproteins. 26082212 1 21 theme desired 205:211 arg1 phenotype 213:221 the desired phenotype 201:221 the desired phenotype of a chosen target organism 201:249 Inverse metabolic engineering (IME) provides a strategy to rapidly identify the genetic elements responsible for the desired phenotype of a chosen target organism. 26082212 3 22 theme libraries 433:441 arg1 generation 398:407 the generation 394:407 the generation of differentially sized libraries from the E. coli W3110 genome followed by high-throughput semiquantitative glycan specific screening 394:542 Here, we describe the generation of differentially sized libraries from the E. coli W3110 genome followed by high-throughput semiquantitative glycan specific screening. 26082212 4 23 theme glycoproteins 713:725 arg1 engineering 645:655 forward engineering 637:655 forward engineering 637:655 DNA sequenced targets demonstrating increased levels of glycan production were selected for forward engineering, protein overexpression, and absolute quantification of glycoproteins. 26082212 4 23 theme glycoproteins 713:725 arg1 overexpression 666:679 protein overexpression 658:679 protein overexpression 658:679 DNA sequenced targets demonstrating increased levels of glycan production were selected for forward engineering, protein overexpression, and absolute quantification of glycoproteins. 26082212 4 23 theme glycoproteins 713:725 arg1 quantification 695:708 absolute quantification 686:708 absolute quantification of glycoproteins 686:725 DNA sequenced targets demonstrating increased levels of glycan production were selected for forward engineering, protein overexpression, and absolute quantification of glycoproteins. 26082212 0 24 theme Enhanced 34:41 arg1 Production 56:65 Enhanced Glycoprotein Production 34:65 Enhanced Glycoprotein Production in Escherichia coli 34:85 Inverse Metabolic Engineering for Enhanced Glycoprotein Production in Escherichia coli. 26082212 4 25 theme increased 581:589 arg1 levels 591:596 increased levels 581:596 increased levels of glycan production 581:617 DNA sequenced targets demonstrating increased levels of glycan production were selected for forward engineering, protein overexpression, and absolute quantification of glycoproteins. 26082212 3 26 dep E. 452:453 arg1 coli 455:458 coli 455:458 coli 455:458 Here, we describe the generation of differentially sized libraries from the E. coli W3110 genome followed by high-throughput semiquantitative glycan specific screening. 26082212 3 27 from genome 466:471 arg1 generation 398:407 the generation 394:407 the generation of differentially sized libraries from the E. coli W3110 genome followed by high-throughput semiquantitative glycan specific screening 394:542 Here, we describe the generation of differentially sized libraries from the E. coli W3110 genome followed by high-throughput semiquantitative glycan specific screening. 26082212 4 28 dep sequenced 549:557 arg1 DNA 545:547 DNA 545:547 DNA 545:547 DNA sequenced targets demonstrating increased levels of glycan production were selected for forward engineering, protein overexpression, and absolute quantification of glycoproteins. 26082212 2 29 theme coli 370:373 arg1 efficiency 344:353 the N-linked glycosylation efficiency 317:353 the N-linked glycosylation efficiency of Escherichia coli 317:373 This methodology has been successfully applied towards enhancing the N-linked glycosylation efficiency of Escherichia coli. 26082212 3 30 theme sized 427:431 arg1 libraries 433:441 differentially sized libraries 412:441 differentially sized libraries 412:441 Here, we describe the generation of differentially sized libraries from the E. coli W3110 genome followed by high-throughput semiquantitative glycan specific screening. 26082212 2 31 link N-linked 321:328 arg1 efficiency 344:353 the N-linked glycosylation efficiency 317:353 the N-linked glycosylation efficiency of Escherichia coli 317:373 This methodology has been successfully applied towards enhancing the N-linked glycosylation efficiency of Escherichia coli. 26082212 3 32 theme semiquantitative 501:516 arg1 screening 534:542 high-throughput semiquantitative glycan specific screening 485:542 high-throughput semiquantitative glycan specific screening 485:542 Here, we describe the generation of differentially sized libraries from the E. coli W3110 genome followed by high-throughput semiquantitative glycan specific screening. 26082212 3 33 theme glycan 518:523 arg1 screening 534:542 high-throughput semiquantitative glycan specific screening 485:542 high-throughput semiquantitative glycan specific screening 485:542 Here, we describe the generation of differentially sized libraries from the E. coli W3110 genome followed by high-throughput semiquantitative glycan specific screening. 26082212 1 34 theme chosen 228:233 arg1 organism 242:249 a chosen target organism 226:249 a chosen target organism 226:249 Inverse metabolic engineering (IME) provides a strategy to rapidly identify the genetic elements responsible for the desired phenotype of a chosen target organism. 26082212 1 35 theme target 235:240 arg1 organism 242:249 a chosen target organism 226:249 a chosen target organism 226:249 Inverse metabolic engineering (IME) provides a strategy to rapidly identify the genetic elements responsible for the desired phenotype of a chosen target organism. 26082212 1 36 theme organism 242:249 arg1 phenotype 213:221 the desired phenotype 201:221 the desired phenotype of a chosen target organism 201:249 Inverse metabolic engineering (IME) provides a strategy to rapidly identify the genetic elements responsible for the desired phenotype of a chosen target organism. 25666817 12 0 theme DSPP 2066:2069 arg1 MMP-20 2056:2061 MMP-20 2056:2061 MMP-20 2056:2061 MMP-20-DSPP specific interaction, excluding other MMP-20-SIBLING pairings, identifies MMP-20 as DSPP cognate MMP. 25666817 12 0 theme DSPP 2066:2069 arg1 MMP 2079:2081 DSPP cognate MMP 2066:2081 DSPP cognate MMP 2066:2081 MMP-20-DSPP specific interaction, excluding other MMP-20-SIBLING pairings, identifies MMP-20 as DSPP cognate MMP. 25666817 12 1 theme MMP-20-SIBLING 2020:2033 arg1 pairings 2035:2042 other MMP-20-SIBLING pairings 2014:2042 other MMP-20-SIBLING pairings 2014:2042 MMP-20-DSPP specific interaction, excluding other MMP-20-SIBLING pairings, identifies MMP-20 as DSPP cognate MMP. 25666817 9 2 theme spectrometry 1626:1637 arg1 analysis 1639:1646 mass spectrometry analysis 1621:1646 mass spectrometry analysis of immunoprecipitation product from OSCC cell lysate, and in situ proximity ligation assays 1621:1738 Colocalization and potential interaction of MMP-20 with dentin sialoprotein was confirmed by coimmunoprecipitation and mass spectrometry analysis of immunoprecipitation product from OSCC cell lysate, and in situ proximity ligation assays. 25666817 6 3 from immunoreactivity 1086:1101 arg1 % 1172:1172 71% 1170:1172 71% 1170:1172 Immunohistochemistry analysis of sections from 21 cases of archived human OSCC tissues showed immunoreactivity for MMP-20 in 18 (86%) and coexpression with DSPP in all 15 cases (71%) positive for DSPP. 25666817 6 3 from immunoreactivity 1086:1101 arg1 18 1117:1118 18 1117:1118 18 1117:1118 Immunohistochemistry analysis of sections from 21 cases of archived human OSCC tissues showed immunoreactivity for MMP-20 in 18 (86%) and coexpression with DSPP in all 15 cases (71%) positive for DSPP. 25666817 6 3 from immunoreactivity 1086:1101 arg1 % 1123:1123 86% 1121:1123 86% 1121:1123 Immunohistochemistry analysis of sections from 21 cases of archived human OSCC tissues showed immunoreactivity for MMP-20 in 18 (86%) and coexpression with DSPP in all 15 cases (71%) positive for DSPP. 25666817 6 3 from immunoreactivity 1086:1101 arg1 cases 1163:1167 all 15 cases 1156:1167 all 15 cases (71%) positive for DSPP 1156:1191 Immunohistochemistry analysis of sections from 21 cases of archived human OSCC tissues showed immunoreactivity for MMP-20 in 18 (86%) and coexpression with DSPP in all 15 cases (71%) positive for DSPP. 25666817 8 4 from analysis 1347:1354 arg1 lines 1369:1373 OSCC cell lines 1359:1373 OSCC cell lines 1359:1373 Western blot and quantitative real-time polymerase chain reaction analysis on OSCC cell lines showed upregulation of MMP-20 protein and mRNA, respectively, while immunofluorescence showed coexpression of MMP-20 and DSPP. 25666817 7 5 theme epithelial 1234:1243 arg1 dysplasia 1245:1253 oral epithelial dysplasia 1229:1253 oral epithelial dysplasia 1229:1253 Similarly, 28 (93%) of 30 cases of oral epithelial dysplasia were positive for MMP-20. 25666817 5 6 theme MMP-20 867:872 arg1 expression 874:883 MMP-20 expression 867:883 MMP-20 expression 867:883 Our goal was to investigate MMP-20 expression and to explore preliminary evidence of its interaction with DSPP in oral squamous cell carcinomas (OSCCs). 25666817 9 7 theme product 1671:1677 arg1 analysis 1639:1646 mass spectrometry analysis 1621:1646 mass spectrometry analysis of immunoprecipitation product from OSCC cell lysate, and in situ proximity ligation assays 1621:1738 Colocalization and potential interaction of MMP-20 with dentin sialoprotein was confirmed by coimmunoprecipitation and mass spectrometry analysis of immunoprecipitation product from OSCC cell lysate, and in situ proximity ligation assays. 25666817 9 7 theme product 1671:1677 arg1 coimmunoprecipitation 1595:1615 coimmunoprecipitation 1595:1615 coimmunoprecipitation 1595:1615 Colocalization and potential interaction of MMP-20 with dentin sialoprotein was confirmed by coimmunoprecipitation and mass spectrometry analysis of immunoprecipitation product from OSCC cell lysate, and in situ proximity ligation assays. 25666817 14 8 theme novel 2205:2209 arg1 findings 2211:2218 These novel findings 2199:2218 These novel findings 2199:2218 These novel findings provide the foundation to explore the mechanisms and significance of DSPP-MMP-20 interaction in oral carcinogenesis. 25666817 3 9 theme Subsequent 548:557 arg1 reports 559:565 Subsequent reports 548:565 Subsequent reports 548:565 Subsequent reports documented possible biological relevance of SIBLING-MMP interaction in vivo by showing that SIBLINGs are always coexpressed with their MMP partners. 25666817 1 10 theme dentin 194:199 arg1 DSPP 222:225 DSPP 222:225 DSPP 222:225 Matrix metalloproteinase 20 (MMP-20), widely regarded as tooth specific, participates with MMP-2 in processing dentin sialophosphoprotein (DSPP) into dentin sialoprotein, dentin phosphoprotein, and dentin glycoprotein. 25666817 1 10 theme dentin 194:199 arg1 sialophosphoprotein 201:219 processing dentin sialophosphoprotein 183:219 processing dentin sialophosphoprotein (DSPP) into dentin sialoprotein, dentin phosphoprotein, and dentin glycoprotein 183:299 Matrix metalloproteinase 20 (MMP-20), widely regarded as tooth specific, participates with MMP-2 in processing dentin sialophosphoprotein (DSPP) into dentin sialoprotein, dentin phosphoprotein, and dentin glycoprotein. 25666817 9 11 theme OSCC 1684:1687 arg1 lysate 1694:1699 OSCC cell lysate 1684:1699 OSCC cell lysate 1684:1699 Colocalization and potential interaction of MMP-20 with dentin sialoprotein was confirmed by coimmunoprecipitation and mass spectrometry analysis of immunoprecipitation product from OSCC cell lysate, and in situ proximity ligation assays. 25666817 2 12 theme biochemical 305:315 arg1 system 317:322 biochemical system 305:322 biochemical system 305:322 In biochemical system, MMP-2, MMP-3, and MMP-9 bind with high affinity to, and are activated by, specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs): bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 25666817 14 13 theme interaction 2301:2311 arg1 significance 2273:2284 significance 2273:2284 significance 2273:2284 These novel findings provide the foundation to explore the mechanisms and significance of DSPP-MMP-20 interaction in oral carcinogenesis. 25666817 14 13 theme interaction 2301:2311 arg1 mechanisms 2258:2267 mechanisms 2258:2267 mechanisms 2258:2267 These novel findings provide the foundation to explore the mechanisms and significance of DSPP-MMP-20 interaction in oral carcinogenesis. 25666817 2 14 theme matrix 516:521 arg1 protein 523:529 dentin matrix protein 1 509:531 dentin matrix protein 1 509:531 In biochemical system, MMP-2, MMP-3, and MMP-9 bind with high affinity to, and are activated by, specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs): bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 25666817 2 14 theme matrix 516:521 arg1 glycoproteins 447:459 specific small integrin-binding ligand N-linked glycoproteins 399:459 specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs) 399:470 In biochemical system, MMP-2, MMP-3, and MMP-9 bind with high affinity to, and are activated by, specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs): bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 25666817 7 15 theme dysplasia 1245:1253 arg1 cases 1220:1224 30 cases 1217:1224 30 cases of oral epithelial dysplasia 1217:1253 Similarly, 28 (93%) of 30 cases of oral epithelial dysplasia were positive for MMP-20. 25666817 9 16 with Colocalization 1502:1515 arg1 sialoprotein 1565:1576 dentin sialoprotein 1558:1576 dentin sialoprotein 1558:1576 Colocalization and potential interaction of MMP-20 with dentin sialoprotein was confirmed by coimmunoprecipitation and mass spectrometry analysis of immunoprecipitation product from OSCC cell lysate, and in situ proximity ligation assays. 25666817 3 17 theme biological 587:596 arg1 relevance 598:606 possible biological relevance 578:606 possible biological relevance of SIBLING-MMP interaction 578:633 Subsequent reports documented possible biological relevance of SIBLING-MMP interaction in vivo by showing that SIBLINGs are always coexpressed with their MMP partners. 25666817 1 18 gly glycoprotein 288:299 arg1 glycoprotein 288:299 dentin glycoprotein 281:299 dentin glycoprotein 281:299 Matrix metalloproteinase 20 (MMP-20), widely regarded as tooth specific, participates with MMP-2 in processing dentin sialophosphoprotein (DSPP) into dentin sialoprotein, dentin phosphoprotein, and dentin glycoprotein. 25666817 12 19 theme MMP-20-DSPP 1970:1980 arg1 interaction 1991:2001 MMP-20-DSPP specific interaction 1970:2001 MMP-20-DSPP specific interaction 1970:2001 MMP-20-DSPP specific interaction, excluding other MMP-20-SIBLING pairings, identifies MMP-20 as DSPP cognate MMP. 25666817 9 20 from analysis 1639:1646 arg1 lysate 1694:1699 OSCC cell lysate 1684:1699 OSCC cell lysate 1684:1699 Colocalization and potential interaction of MMP-20 with dentin sialoprotein was confirmed by coimmunoprecipitation and mass spectrometry analysis of immunoprecipitation product from OSCC cell lysate, and in situ proximity ligation assays. 25666817 9 20 from analysis 1639:1646 arg1 assays 1733:1738 in situ proximity ligation assays 1706:1738 in situ proximity ligation assays 1706:1738 Colocalization and potential interaction of MMP-20 with dentin sialoprotein was confirmed by coimmunoprecipitation and mass spectrometry analysis of immunoprecipitation product from OSCC cell lysate, and in situ proximity ligation assays. 25666817 10 21 theme immunoprecipation 1777:1793 arg1 results 1756:1762 results 1756:1762 results of chromatin immunoprecipation 1756:1793 Significantly, results of chromatin immunoprecipation revealed a 9-fold enrichment of DSPP at MMP-20 promoter-proximal elements. 25666817 8 22 theme protein 1405:1411 arg1 upregulation 1382:1393 upregulation 1382:1393 upregulation of MMP-20 protein and mRNA 1382:1420 Western blot and quantitative real-time polymerase chain reaction analysis on OSCC cell lines showed upregulation of MMP-20 protein and mRNA, respectively, while immunofluorescence showed coexpression of MMP-20 and DSPP. 25666817 3 23 theme interaction 623:633 arg1 relevance 598:606 possible biological relevance 578:606 possible biological relevance of SIBLING-MMP interaction 578:633 Subsequent reports documented possible biological relevance of SIBLING-MMP interaction in vivo by showing that SIBLINGs are always coexpressed with their MMP partners. 25666817 9 24 theme ligation 1724:1731 arg1 assays 1733:1738 in situ proximity ligation assays 1706:1738 in situ proximity ligation assays 1706:1738 Colocalization and potential interaction of MMP-20 with dentin sialoprotein was confirmed by coimmunoprecipitation and mass spectrometry analysis of immunoprecipitation product from OSCC cell lysate, and in situ proximity ligation assays. 25666817 8 25 theme mRNA 1417:1420 arg1 upregulation 1382:1393 upregulation 1382:1393 upregulation of MMP-20 protein and mRNA 1382:1420 Western blot and quantitative real-time polymerase chain reaction analysis on OSCC cell lines showed upregulation of MMP-20 protein and mRNA, respectively, while immunofluorescence showed coexpression of MMP-20 and DSPP. 25666817 14 26 from mechanisms 2258:2267 arg1 carcinogenesis 2321:2334 oral carcinogenesis 2316:2334 oral carcinogenesis 2316:2334 These novel findings provide the foundation to explore the mechanisms and significance of DSPP-MMP-20 interaction in oral carcinogenesis. 25666817 13 27 theme strong 2101:2106 arg1 enrichment 2113:2122 the strong DSPP enrichment 2097:2122 the strong DSPP enrichment at the MMP-20 promoter 2097:2145 Furthermore, the strong DSPP enrichment at the MMP-20 promoter suggests a regulatory role in MMP-20 transcription. 25666817 6 28 theme Immunohistochemistry 992:1011 arg1 analysis 1013:1020 Immunohistochemistry analysis 992:1020 Immunohistochemistry analysis of sections from 21 cases of archived human OSCC tissues 992:1077 Immunohistochemistry analysis of sections from 21 cases of archived human OSCC tissues showed immunoreactivity for MMP-20 in 18 (86%) and coexpression with DSPP in all 15 cases (71%) positive for DSPP. 25666817 10 29 theme DSPP 1827:1830 arg1 enrichment 1813:1822 a 9-fold enrichment 1804:1822 a 9-fold enrichment of DSPP at MMP-20 promoter-proximal elements 1804:1867 Significantly, results of chromatin immunoprecipation revealed a 9-fold enrichment of DSPP at MMP-20 promoter-proximal elements. 25666817 4 30 theme other 748:752 arg1 SIBLINGs-DSPP 754:766 2 other SIBLINGs-DSPP 746:766 2 other SIBLINGs-DSPP 746:766 However, the cognate MMPs for 2 other SIBLINGs-DSPP and matrix extracellular phosphogylcoprotein-are yet to be identified. 25666817 1 31 theme Matrix 83:88 arg1 metalloproteinase 90:106 Matrix metalloproteinase 20 83:109 Matrix metalloproteinase 20 (MMP-20) 83:118 Matrix metalloproteinase 20 (MMP-20), widely regarded as tooth specific, participates with MMP-2 in processing dentin sialophosphoprotein (DSPP) into dentin sialoprotein, dentin phosphoprotein, and dentin glycoprotein. 25666817 1 31 theme Matrix 83:88 arg1 MMP-20 112:117 MMP-20 112:117 MMP-20 112:117 Matrix metalloproteinase 20 (MMP-20), widely regarded as tooth specific, participates with MMP-2 in processing dentin sialophosphoprotein (DSPP) into dentin sialoprotein, dentin phosphoprotein, and dentin glycoprotein. 25666817 5 32 with interaction 928:938 arg1 DSPP 945:948 DSPP 945:948 DSPP 945:948 Our goal was to investigate MMP-20 expression and to explore preliminary evidence of its interaction with DSPP in oral squamous cell carcinomas (OSCCs). 25666817 6 33 theme archived 1051:1058 arg1 tissues 1071:1077 archived human OSCC tissues 1051:1077 archived human OSCC tissues 1051:1077 Immunohistochemistry analysis of sections from 21 cases of archived human OSCC tissues showed immunoreactivity for MMP-20 in 18 (86%) and coexpression with DSPP in all 15 cases (71%) positive for DSPP. 25666817 8 34 theme Western 1281:1287 arg1 blot 1289:1292 Western blot 1281:1292 Western blot 1281:1292 Western blot and quantitative real-time polymerase chain reaction analysis on OSCC cell lines showed upregulation of MMP-20 protein and mRNA, respectively, while immunofluorescence showed coexpression of MMP-20 and DSPP. 25666817 9 35 dep in 1706:1707 arg1 situ 1709:1712 situ 1709:1712 situ 1709:1712 Colocalization and potential interaction of MMP-20 with dentin sialoprotein was confirmed by coimmunoprecipitation and mass spectrometry analysis of immunoprecipitation product from OSCC cell lysate, and in situ proximity ligation assays. 25666817 5 36 from interaction 928:938 arg1 carcinomas 972:981 oral squamous cell carcinomas 953:981 oral squamous cell carcinomas (OSCCs) 953:989 Our goal was to investigate MMP-20 expression and to explore preliminary evidence of its interaction with DSPP in oral squamous cell carcinomas (OSCCs). 25666817 5 36 from interaction 928:938 arg1 OSCCs 984:988 OSCCs 984:988 OSCCs 984:988 Our goal was to investigate MMP-20 expression and to explore preliminary evidence of its interaction with DSPP in oral squamous cell carcinomas (OSCCs). 25666817 2 37 theme ligand 431:436 arg1 protein 523:529 dentin matrix protein 1 509:531 dentin matrix protein 1 509:531 In biochemical system, MMP-2, MMP-3, and MMP-9 bind with high affinity to, and are activated by, specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs): bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 25666817 2 37 theme ligand 431:436 arg1 glycoproteins 447:459 specific small integrin-binding ligand N-linked glycoproteins 399:459 specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs) 399:470 In biochemical system, MMP-2, MMP-3, and MMP-9 bind with high affinity to, and are activated by, specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs): bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 25666817 2 37 theme ligand 431:436 arg1 sialoprotein 478:489 bone sialoprotein 473:489 bone sialoprotein 473:489 In biochemical system, MMP-2, MMP-3, and MMP-9 bind with high affinity to, and are activated by, specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs): bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 25666817 2 37 theme ligand 431:436 arg1 SIBLINGs 462:469 SIBLINGs 462:469 SIBLINGs 462:469 In biochemical system, MMP-2, MMP-3, and MMP-9 bind with high affinity to, and are activated by, specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs): bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 25666817 2 37 theme ligand 431:436 arg1 osteopontin 492:502 osteopontin 492:502 osteopontin 492:502 In biochemical system, MMP-2, MMP-3, and MMP-9 bind with high affinity to, and are activated by, specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs): bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 25666817 0 38 from interaction 55:65 arg1 cancer 75:80 oral cancer 70:80 oral cancer 70:80 Matrix metalloproteinase 20-dentin sialophosphoprotein interaction in oral cancer. 25666817 6 39 from analysis 1013:1020 arg1 cases 1042:1046 21 cases 1039:1046 21 cases of archived human OSCC tissues 1039:1077 Immunohistochemistry analysis of sections from 21 cases of archived human OSCC tissues showed immunoreactivity for MMP-20 in 18 (86%) and coexpression with DSPP in all 15 cases (71%) positive for DSPP. 25666817 2 40 link N-linked 438:445 arg1 protein 523:529 dentin matrix protein 1 509:531 dentin matrix protein 1 509:531 In biochemical system, MMP-2, MMP-3, and MMP-9 bind with high affinity to, and are activated by, specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs): bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 25666817 2 40 link N-linked 438:445 arg1 glycoproteins 447:459 specific small integrin-binding ligand N-linked glycoproteins 399:459 specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs) 399:470 In biochemical system, MMP-2, MMP-3, and MMP-9 bind with high affinity to, and are activated by, specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs): bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 25666817 2 40 link N-linked 438:445 arg1 sialoprotein 478:489 bone sialoprotein 473:489 bone sialoprotein 473:489 In biochemical system, MMP-2, MMP-3, and MMP-9 bind with high affinity to, and are activated by, specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs): bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 25666817 2 40 link N-linked 438:445 arg1 SIBLINGs 462:469 SIBLINGs 462:469 SIBLINGs 462:469 In biochemical system, MMP-2, MMP-3, and MMP-9 bind with high affinity to, and are activated by, specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs): bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 25666817 2 40 link N-linked 438:445 arg1 osteopontin 492:502 osteopontin 492:502 osteopontin 492:502 In biochemical system, MMP-2, MMP-3, and MMP-9 bind with high affinity to, and are activated by, specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs): bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 25666817 4 41 theme cognate 729:735 arg1 MMPs 737:740 the cognate MMPs 725:740 the cognate MMPs for 2 other SIBLINGs-DSPP and matrix extracellular phosphogylcoprotein-are 725:815 However, the cognate MMPs for 2 other SIBLINGs-DSPP and matrix extracellular phosphogylcoprotein-are yet to be identified. 25666817 0 42 theme Matrix 0:5 arg1 metalloproteinase 7:23 Matrix metalloproteinase 0:23 Matrix metalloproteinase 0:23 Matrix metalloproteinase 20-dentin sialophosphoprotein interaction in oral cancer. 25666817 1 43 theme dentin 281:286 arg1 glycoprotein 288:299 dentin glycoprotein 281:299 dentin glycoprotein 281:299 Matrix metalloproteinase 20 (MMP-20), widely regarded as tooth specific, participates with MMP-2 in processing dentin sialophosphoprotein (DSPP) into dentin sialoprotein, dentin phosphoprotein, and dentin glycoprotein. 25666817 11 44 contain has 1908:1910 arg2 distribution 1927:1938 a wider tissue distribution 1912:1938 a wider tissue distribution than previously acknowledged 1912:1967 Our data provide evidence that MMP-20 has a wider tissue distribution than previously acknowledged. 25666817 11 44 contain has 1908:1910 arg1 MMP-20 1901:1906 MMP-20 1901:1906 MMP-20 1901:1906 Our data provide evidence that MMP-20 has a wider tissue distribution than previously acknowledged. 25666817 9 45 theme potential 1521:1529 arg1 interaction 1531:1541 potential interaction 1521:1541 potential interaction of MMP-20 with dentin sialoprotein 1521:1576 Colocalization and potential interaction of MMP-20 with dentin sialoprotein was confirmed by coimmunoprecipitation and mass spectrometry analysis of immunoprecipitation product from OSCC cell lysate, and in situ proximity ligation assays. 25666817 6 46 theme OSCC 1066:1069 arg1 tissues 1071:1077 archived human OSCC tissues 1051:1077 archived human OSCC tissues 1051:1077 Immunohistochemistry analysis of sections from 21 cases of archived human OSCC tissues showed immunoreactivity for MMP-20 in 18 (86%) and coexpression with DSPP in all 15 cases (71%) positive for DSPP. 25666817 2 47 theme small 408:412 arg1 protein 523:529 dentin matrix protein 1 509:531 dentin matrix protein 1 509:531 In biochemical system, MMP-2, MMP-3, and MMP-9 bind with high affinity to, and are activated by, specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs): bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 25666817 2 47 theme small 408:412 arg1 glycoproteins 447:459 specific small integrin-binding ligand N-linked glycoproteins 399:459 specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs) 399:470 In biochemical system, MMP-2, MMP-3, and MMP-9 bind with high affinity to, and are activated by, specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs): bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 25666817 2 47 theme small 408:412 arg1 sialoprotein 478:489 bone sialoprotein 473:489 bone sialoprotein 473:489 In biochemical system, MMP-2, MMP-3, and MMP-9 bind with high affinity to, and are activated by, specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs): bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 25666817 2 47 theme small 408:412 arg1 SIBLINGs 462:469 SIBLINGs 462:469 SIBLINGs 462:469 In biochemical system, MMP-2, MMP-3, and MMP-9 bind with high affinity to, and are activated by, specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs): bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 25666817 2 47 theme small 408:412 arg1 osteopontin 492:502 osteopontin 492:502 osteopontin 492:502 In biochemical system, MMP-2, MMP-3, and MMP-9 bind with high affinity to, and are activated by, specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs): bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 25666817 8 48 theme real-time 1311:1319 arg1 reaction 1338:1345 quantitative real-time polymerase chain reaction 1298:1345 quantitative real-time polymerase chain reaction analysis 1298:1354 Western blot and quantitative real-time polymerase chain reaction analysis on OSCC cell lines showed upregulation of MMP-20 protein and mRNA, respectively, while immunofluorescence showed coexpression of MMP-20 and DSPP. 25666817 5 49 theme squamous 958:965 arg1 carcinomas 972:981 oral squamous cell carcinomas 953:981 oral squamous cell carcinomas (OSCCs) 953:989 Our goal was to investigate MMP-20 expression and to explore preliminary evidence of its interaction with DSPP in oral squamous cell carcinomas (OSCCs). 25666817 5 49 theme squamous 958:965 arg1 OSCCs 984:988 OSCCs 984:988 OSCCs 984:988 Our goal was to investigate MMP-20 expression and to explore preliminary evidence of its interaction with DSPP in oral squamous cell carcinomas (OSCCs). 25666817 7 50 theme oral 1229:1232 arg1 dysplasia 1245:1253 oral epithelial dysplasia 1229:1253 oral epithelial dysplasia 1229:1253 Similarly, 28 (93%) of 30 cases of oral epithelial dysplasia were positive for MMP-20. 25666817 13 51 from role 2169:2172 arg1 transcription 2184:2196 MMP-20 transcription 2177:2196 MMP-20 transcription 2177:2196 Furthermore, the strong DSPP enrichment at the MMP-20 promoter suggests a regulatory role in MMP-20 transcription. 25666817 8 52 theme chain 1332:1336 arg1 reaction 1338:1345 quantitative real-time polymerase chain reaction 1298:1345 quantitative real-time polymerase chain reaction analysis 1298:1354 Western blot and quantitative real-time polymerase chain reaction analysis on OSCC cell lines showed upregulation of MMP-20 protein and mRNA, respectively, while immunofluorescence showed coexpression of MMP-20 and DSPP. 25666817 11 53 theme wider 1914:1918 arg1 distribution 1927:1938 a wider tissue distribution 1912:1938 a wider tissue distribution than previously acknowledged 1912:1967 Our data provide evidence that MMP-20 has a wider tissue distribution than previously acknowledged. 25666817 6 54 with immunoreactivity 1086:1101 arg1 DSPP 1148:1151 DSPP 1148:1151 DSPP 1148:1151 Immunohistochemistry analysis of sections from 21 cases of archived human OSCC tissues showed immunoreactivity for MMP-20 in 18 (86%) and coexpression with DSPP in all 15 cases (71%) positive for DSPP. 25666817 7 55 theme cases 1220:1224 arg1 28 1205:1206 28 1205:1206 28 1205:1206 Similarly, 28 (93%) of 30 cases of oral epithelial dysplasia were positive for MMP-20. 25666817 7 55 theme cases 1220:1224 arg1 % 1211:1211 93% 1209:1211 93% 1209:1211 Similarly, 28 (93%) of 30 cases of oral epithelial dysplasia were positive for MMP-20. 25666817 7 55 theme cases 1220:1224 arg1 cases 1220:1224 30 cases 1217:1224 30 cases of oral epithelial dysplasia 1217:1253 Similarly, 28 (93%) of 30 cases of oral epithelial dysplasia were positive for MMP-20. 25666817 10 56 theme MMP-20 1835:1840 arg1 elements 1860:1867 MMP-20 promoter-proximal elements 1835:1867 MMP-20 promoter-proximal elements 1835:1867 Significantly, results of chromatin immunoprecipation revealed a 9-fold enrichment of DSPP at MMP-20 promoter-proximal elements. 25666817 0 57 theme oral 70:73 arg1 cancer 75:80 oral cancer 70:80 oral cancer 70:80 Matrix metalloproteinase 20-dentin sialophosphoprotein interaction in oral cancer. 25666817 2 58 gly glycoproteins 447:459 arg1 protein 523:529 dentin matrix protein 1 509:531 dentin matrix protein 1 509:531 In biochemical system, MMP-2, MMP-3, and MMP-9 bind with high affinity to, and are activated by, specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs): bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 25666817 2 58 gly glycoproteins 447:459 arg1 glycoproteins 447:459 specific small integrin-binding ligand N-linked glycoproteins 399:459 specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs) 399:470 In biochemical system, MMP-2, MMP-3, and MMP-9 bind with high affinity to, and are activated by, specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs): bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 25666817 2 58 gly glycoproteins 447:459 arg1 sialoprotein 478:489 bone sialoprotein 473:489 bone sialoprotein 473:489 In biochemical system, MMP-2, MMP-3, and MMP-9 bind with high affinity to, and are activated by, specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs): bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 25666817 2 58 gly glycoproteins 447:459 arg1 SIBLINGs 462:469 SIBLINGs 462:469 SIBLINGs 462:469 In biochemical system, MMP-2, MMP-3, and MMP-9 bind with high affinity to, and are activated by, specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs): bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 25666817 2 58 gly glycoproteins 447:459 arg1 osteopontin 492:502 osteopontin 492:502 osteopontin 492:502 In biochemical system, MMP-2, MMP-3, and MMP-9 bind with high affinity to, and are activated by, specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs): bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 25666817 8 59 theme OSCC 1359:1362 arg1 lines 1369:1373 OSCC cell lines 1359:1373 OSCC cell lines 1359:1373 Western blot and quantitative real-time polymerase chain reaction analysis on OSCC cell lines showed upregulation of MMP-20 protein and mRNA, respectively, while immunofluorescence showed coexpression of MMP-20 and DSPP. 25666817 2 60 theme high 359:362 arg1 affinity 364:371 high affinity 359:371 high affinity 359:371 In biochemical system, MMP-2, MMP-3, and MMP-9 bind with high affinity to, and are activated by, specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs): bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 25666817 3 61 theme MMP 702:704 arg1 partners 706:713 their MMP partners 696:713 their MMP partners 696:713 Subsequent reports documented possible biological relevance of SIBLING-MMP interaction in vivo by showing that SIBLINGs are always coexpressed with their MMP partners. 25666817 1 62 theme dentin 254:259 arg1 phosphoprotein 261:274 dentin phosphoprotein 254:274 dentin phosphoprotein 254:274 Matrix metalloproteinase 20 (MMP-20), widely regarded as tooth specific, participates with MMP-2 in processing dentin sialophosphoprotein (DSPP) into dentin sialoprotein, dentin phosphoprotein, and dentin glycoprotein. 25666817 10 63 from elements 1860:1867 arg1 enrichment 1813:1822 a 9-fold enrichment 1804:1822 a 9-fold enrichment of DSPP at MMP-20 promoter-proximal elements 1804:1867 Significantly, results of chromatin immunoprecipation revealed a 9-fold enrichment of DSPP at MMP-20 promoter-proximal elements. 25666817 9 64 theme mass 1621:1624 arg1 analysis 1639:1646 mass spectrometry analysis 1621:1646 mass spectrometry analysis of immunoprecipitation product from OSCC cell lysate, and in situ proximity ligation assays 1621:1738 Colocalization and potential interaction of MMP-20 with dentin sialoprotein was confirmed by coimmunoprecipitation and mass spectrometry analysis of immunoprecipitation product from OSCC cell lysate, and in situ proximity ligation assays. 25666817 8 65 from blot 1289:1292 arg1 lines 1369:1373 OSCC cell lines 1359:1373 OSCC cell lines 1359:1373 Western blot and quantitative real-time polymerase chain reaction analysis on OSCC cell lines showed upregulation of MMP-20 protein and mRNA, respectively, while immunofluorescence showed coexpression of MMP-20 and DSPP. 25666817 13 66 theme MMP-20 2177:2182 arg1 transcription 2184:2196 MMP-20 transcription 2177:2196 MMP-20 transcription 2177:2196 Furthermore, the strong DSPP enrichment at the MMP-20 promoter suggests a regulatory role in MMP-20 transcription. 25666817 12 67 theme other 2014:2018 arg1 pairings 2035:2042 other MMP-20-SIBLING pairings 2014:2042 other MMP-20-SIBLING pairings 2014:2042 MMP-20-DSPP specific interaction, excluding other MMP-20-SIBLING pairings, identifies MMP-20 as DSPP cognate MMP. 25666817 13 68 from promoter 2138:2145 arg1 enrichment 2113:2122 the strong DSPP enrichment 2097:2122 the strong DSPP enrichment at the MMP-20 promoter 2097:2145 Furthermore, the strong DSPP enrichment at the MMP-20 promoter suggests a regulatory role in MMP-20 transcription. 25666817 9 69 theme immunoprecipitation 1651:1669 arg1 product 1671:1677 immunoprecipitation product 1651:1677 immunoprecipitation product from OSCC cell lysate, and in situ proximity ligation assays 1651:1738 Colocalization and potential interaction of MMP-20 with dentin sialoprotein was confirmed by coimmunoprecipitation and mass spectrometry analysis of immunoprecipitation product from OSCC cell lysate, and in situ proximity ligation assays. 25666817 9 70 with interaction 1531:1541 arg1 sialoprotein 1565:1576 dentin sialoprotein 1558:1576 dentin sialoprotein 1558:1576 Colocalization and potential interaction of MMP-20 with dentin sialoprotein was confirmed by coimmunoprecipitation and mass spectrometry analysis of immunoprecipitation product from OSCC cell lysate, and in situ proximity ligation assays. 25666817 6 71 from cases 1042:1046 arg1 sections 1025:1032 sections 1025:1032 sections from 21 cases of archived human OSCC tissues 1025:1077 Immunohistochemistry analysis of sections from 21 cases of archived human OSCC tissues showed immunoreactivity for MMP-20 in 18 (86%) and coexpression with DSPP in all 15 cases (71%) positive for DSPP. 25666817 6 71 from cases 1042:1046 arg1 analysis 1013:1020 Immunohistochemistry analysis 992:1020 Immunohistochemistry analysis of sections from 21 cases of archived human OSCC tissues 992:1077 Immunohistochemistry analysis of sections from 21 cases of archived human OSCC tissues showed immunoreactivity for MMP-20 in 18 (86%) and coexpression with DSPP in all 15 cases (71%) positive for DSPP. 25666817 10 72 theme chromatin 1767:1775 arg1 immunoprecipation 1777:1793 chromatin immunoprecipation 1767:1793 chromatin immunoprecipation 1767:1793 Significantly, results of chromatin immunoprecipation revealed a 9-fold enrichment of DSPP at MMP-20 promoter-proximal elements. 25666817 1 73 theme processing 183:192 arg1 DSPP 222:225 DSPP 222:225 DSPP 222:225 Matrix metalloproteinase 20 (MMP-20), widely regarded as tooth specific, participates with MMP-2 in processing dentin sialophosphoprotein (DSPP) into dentin sialoprotein, dentin phosphoprotein, and dentin glycoprotein. 25666817 1 73 theme processing 183:192 arg1 sialophosphoprotein 201:219 processing dentin sialophosphoprotein 183:219 processing dentin sialophosphoprotein (DSPP) into dentin sialoprotein, dentin phosphoprotein, and dentin glycoprotein 183:299 Matrix metalloproteinase 20 (MMP-20), widely regarded as tooth specific, participates with MMP-2 in processing dentin sialophosphoprotein (DSPP) into dentin sialoprotein, dentin phosphoprotein, and dentin glycoprotein. 25666817 12 74 theme specific 1982:1989 arg1 interaction 1991:2001 MMP-20-DSPP specific interaction 1970:2001 MMP-20-DSPP specific interaction 1970:2001 MMP-20-DSPP specific interaction, excluding other MMP-20-SIBLING pairings, identifies MMP-20 as DSPP cognate MMP. 25666817 9 75 theme cell 1689:1692 arg1 lysate 1694:1699 OSCC cell lysate 1684:1699 OSCC cell lysate 1684:1699 Colocalization and potential interaction of MMP-20 with dentin sialoprotein was confirmed by coimmunoprecipitation and mass spectrometry analysis of immunoprecipitation product from OSCC cell lysate, and in situ proximity ligation assays. 25666817 3 76 theme possible 578:585 arg1 relevance 598:606 possible biological relevance 578:606 possible biological relevance of SIBLING-MMP interaction 578:633 Subsequent reports documented possible biological relevance of SIBLING-MMP interaction in vivo by showing that SIBLINGs are always coexpressed with their MMP partners. 25666817 6 77 with coexpression 1130:1141 arg1 DSPP 1148:1151 DSPP 1148:1151 DSPP 1148:1151 Immunohistochemistry analysis of sections from 21 cases of archived human OSCC tissues showed immunoreactivity for MMP-20 in 18 (86%) and coexpression with DSPP in all 15 cases (71%) positive for DSPP. 25666817 2 78 theme dentin 509:514 arg1 protein 523:529 dentin matrix protein 1 509:531 dentin matrix protein 1 509:531 In biochemical system, MMP-2, MMP-3, and MMP-9 bind with high affinity to, and are activated by, specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs): bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 25666817 2 78 theme dentin 509:514 arg1 glycoproteins 447:459 specific small integrin-binding ligand N-linked glycoproteins 399:459 specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs) 399:470 In biochemical system, MMP-2, MMP-3, and MMP-9 bind with high affinity to, and are activated by, specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs): bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 25666817 8 79 theme MMP-20 1398:1403 arg1 protein 1405:1411 MMP-20 protein 1398:1411 MMP-20 protein 1398:1411 Western blot and quantitative real-time polymerase chain reaction analysis on OSCC cell lines showed upregulation of MMP-20 protein and mRNA, respectively, while immunofluorescence showed coexpression of MMP-20 and DSPP. 25666817 13 80 theme regulatory 2158:2167 arg1 role 2169:2172 a regulatory role 2156:2172 a regulatory role in MMP-20 transcription 2156:2196 Furthermore, the strong DSPP enrichment at the MMP-20 promoter suggests a regulatory role in MMP-20 transcription. 25666817 9 81 theme in 1706:1707 arg1 assays 1733:1738 in situ proximity ligation assays 1706:1738 in situ proximity ligation assays 1706:1738 Colocalization and potential interaction of MMP-20 with dentin sialoprotein was confirmed by coimmunoprecipitation and mass spectrometry analysis of immunoprecipitation product from OSCC cell lysate, and in situ proximity ligation assays. 25666817 6 82 theme positive 1175:1182 arg1 % 1172:1172 71% 1170:1172 71% 1170:1172 Immunohistochemistry analysis of sections from 21 cases of archived human OSCC tissues showed immunoreactivity for MMP-20 in 18 (86%) and coexpression with DSPP in all 15 cases (71%) positive for DSPP. 25666817 6 82 theme positive 1175:1182 arg1 cases 1163:1167 all 15 cases 1156:1167 all 15 cases (71%) positive for DSPP 1156:1191 Immunohistochemistry analysis of sections from 21 cases of archived human OSCC tissues showed immunoreactivity for MMP-20 in 18 (86%) and coexpression with DSPP in all 15 cases (71%) positive for DSPP. 25666817 4 83 theme extracellular 779:791 arg1 phosphogylcoprotein-are 793:815 matrix extracellular phosphogylcoprotein-are 772:815 matrix extracellular phosphogylcoprotein-are 772:815 However, the cognate MMPs for 2 other SIBLINGs-DSPP and matrix extracellular phosphogylcoprotein-are yet to be identified. 25666817 3 84 theme SIBLING-MMP 611:621 arg1 interaction 623:633 SIBLING-MMP interaction 611:633 SIBLING-MMP interaction 611:633 Subsequent reports documented possible biological relevance of SIBLING-MMP interaction in vivo by showing that SIBLINGs are always coexpressed with their MMP partners. 25666817 5 85 theme interaction 928:938 arg1 evidence 912:919 preliminary evidence 900:919 preliminary evidence of its interaction with DSPP in oral squamous cell carcinomas (OSCCs) 900:989 Our goal was to investigate MMP-20 expression and to explore preliminary evidence of its interaction with DSPP in oral squamous cell carcinomas (OSCCs). 25666817 9 86 theme proximity 1714:1722 arg1 assays 1733:1738 in situ proximity ligation assays 1706:1738 in situ proximity ligation assays 1706:1738 Colocalization and potential interaction of MMP-20 with dentin sialoprotein was confirmed by coimmunoprecipitation and mass spectrometry analysis of immunoprecipitation product from OSCC cell lysate, and in situ proximity ligation assays. 25666817 14 87 from significance 2273:2284 arg1 carcinogenesis 2321:2334 oral carcinogenesis 2316:2334 oral carcinogenesis 2316:2334 These novel findings provide the foundation to explore the mechanisms and significance of DSPP-MMP-20 interaction in oral carcinogenesis. 25666817 13 88 theme MMP-20 2131:2136 arg1 promoter 2138:2145 the MMP-20 promoter 2127:2145 the MMP-20 promoter 2127:2145 Furthermore, the strong DSPP enrichment at the MMP-20 promoter suggests a regulatory role in MMP-20 transcription. 25666817 6 89 theme sections 1025:1032 arg1 analysis 1013:1020 Immunohistochemistry analysis 992:1020 Immunohistochemistry analysis of sections from 21 cases of archived human OSCC tissues 992:1077 Immunohistochemistry analysis of sections from 21 cases of archived human OSCC tissues showed immunoreactivity for MMP-20 in 18 (86%) and coexpression with DSPP in all 15 cases (71%) positive for DSPP. 25666817 2 90 theme bone 473:476 arg1 glycoproteins 447:459 specific small integrin-binding ligand N-linked glycoproteins 399:459 specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs) 399:470 In biochemical system, MMP-2, MMP-3, and MMP-9 bind with high affinity to, and are activated by, specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs): bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 25666817 2 90 theme bone 473:476 arg1 sialoprotein 478:489 bone sialoprotein 473:489 bone sialoprotein 473:489 In biochemical system, MMP-2, MMP-3, and MMP-9 bind with high affinity to, and are activated by, specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs): bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 25666817 12 91 theme cognate 2071:2077 arg1 MMP-20 2056:2061 MMP-20 2056:2061 MMP-20 2056:2061 MMP-20-DSPP specific interaction, excluding other MMP-20-SIBLING pairings, identifies MMP-20 as DSPP cognate MMP. 25666817 12 91 theme cognate 2071:2077 arg1 MMP 2079:2081 DSPP cognate MMP 2066:2081 DSPP cognate MMP 2066:2081 MMP-20-DSPP specific interaction, excluding other MMP-20-SIBLING pairings, identifies MMP-20 as DSPP cognate MMP. 25666817 2 92 dep glycoproteins 447:459 arg1 protein 523:529 dentin matrix protein 1 509:531 dentin matrix protein 1 509:531 In biochemical system, MMP-2, MMP-3, and MMP-9 bind with high affinity to, and are activated by, specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs): bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 25666817 2 92 dep glycoproteins 447:459 arg1 osteopontin 492:502 osteopontin 492:502 osteopontin 492:502 In biochemical system, MMP-2, MMP-3, and MMP-9 bind with high affinity to, and are activated by, specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs): bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 25666817 2 92 dep glycoproteins 447:459 arg1 sialoprotein 478:489 bone sialoprotein 473:489 bone sialoprotein 473:489 In biochemical system, MMP-2, MMP-3, and MMP-9 bind with high affinity to, and are activated by, specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs): bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 25666817 2 92 dep glycoproteins 447:459 arg1 glycoproteins 447:459 specific small integrin-binding ligand N-linked glycoproteins 399:459 specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs) 399:470 In biochemical system, MMP-2, MMP-3, and MMP-9 bind with high affinity to, and are activated by, specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs): bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 25666817 5 93 theme preliminary 900:910 arg1 evidence 912:919 preliminary evidence 900:919 preliminary evidence of its interaction with DSPP in oral squamous cell carcinomas (OSCCs) 900:989 Our goal was to investigate MMP-20 expression and to explore preliminary evidence of its interaction with DSPP in oral squamous cell carcinomas (OSCCs). 25666817 9 94 from lysate 1694:1699 arg1 analysis 1639:1646 mass spectrometry analysis 1621:1646 mass spectrometry analysis of immunoprecipitation product from OSCC cell lysate, and in situ proximity ligation assays 1621:1738 Colocalization and potential interaction of MMP-20 with dentin sialoprotein was confirmed by coimmunoprecipitation and mass spectrometry analysis of immunoprecipitation product from OSCC cell lysate, and in situ proximity ligation assays. 25666817 9 94 from lysate 1694:1699 arg1 product 1671:1677 immunoprecipitation product 1651:1677 immunoprecipitation product from OSCC cell lysate, and in situ proximity ligation assays 1651:1738 Colocalization and potential interaction of MMP-20 with dentin sialoprotein was confirmed by coimmunoprecipitation and mass spectrometry analysis of immunoprecipitation product from OSCC cell lysate, and in situ proximity ligation assays. 25666817 9 94 from lysate 1694:1699 arg1 coimmunoprecipitation 1595:1615 coimmunoprecipitation 1595:1615 coimmunoprecipitation 1595:1615 Colocalization and potential interaction of MMP-20 with dentin sialoprotein was confirmed by coimmunoprecipitation and mass spectrometry analysis of immunoprecipitation product from OSCC cell lysate, and in situ proximity ligation assays. 25666817 13 95 theme DSPP 2108:2111 arg1 enrichment 2113:2122 the strong DSPP enrichment 2097:2122 the strong DSPP enrichment at the MMP-20 promoter 2097:2145 Furthermore, the strong DSPP enrichment at the MMP-20 promoter suggests a regulatory role in MMP-20 transcription. 25666817 5 96 from evidence 912:919 arg1 carcinomas 972:981 oral squamous cell carcinomas 953:981 oral squamous cell carcinomas (OSCCs) 953:989 Our goal was to investigate MMP-20 expression and to explore preliminary evidence of its interaction with DSPP in oral squamous cell carcinomas (OSCCs). 25666817 5 96 from evidence 912:919 arg1 OSCCs 984:988 OSCCs 984:988 OSCCs 984:988 Our goal was to investigate MMP-20 expression and to explore preliminary evidence of its interaction with DSPP in oral squamous cell carcinomas (OSCCs). 25666817 5 97 theme cell 967:970 arg1 carcinomas 972:981 oral squamous cell carcinomas 953:981 oral squamous cell carcinomas (OSCCs) 953:989 Our goal was to investigate MMP-20 expression and to explore preliminary evidence of its interaction with DSPP in oral squamous cell carcinomas (OSCCs). 25666817 5 97 theme cell 967:970 arg1 OSCCs 984:988 OSCCs 984:988 OSCCs 984:988 Our goal was to investigate MMP-20 expression and to explore preliminary evidence of its interaction with DSPP in oral squamous cell carcinomas (OSCCs). 25666817 9 98 from coimmunoprecipitation 1595:1615 arg1 lysate 1694:1699 OSCC cell lysate 1684:1699 OSCC cell lysate 1684:1699 Colocalization and potential interaction of MMP-20 with dentin sialoprotein was confirmed by coimmunoprecipitation and mass spectrometry analysis of immunoprecipitation product from OSCC cell lysate, and in situ proximity ligation assays. 25666817 9 98 from coimmunoprecipitation 1595:1615 arg1 assays 1733:1738 in situ proximity ligation assays 1706:1738 in situ proximity ligation assays 1706:1738 Colocalization and potential interaction of MMP-20 with dentin sialoprotein was confirmed by coimmunoprecipitation and mass spectrometry analysis of immunoprecipitation product from OSCC cell lysate, and in situ proximity ligation assays. 25666817 14 99 dep mechanisms 2258:2267 arg1 the 2254:2256 the 2254:2256 the 2254:2256 These novel findings provide the foundation to explore the mechanisms and significance of DSPP-MMP-20 interaction in oral carcinogenesis. 25666817 8 100 theme MMP-20 1485:1490 arg1 coexpression 1469:1480 coexpression 1469:1480 coexpression of MMP-20 and DSPP 1469:1499 Western blot and quantitative real-time polymerase chain reaction analysis on OSCC cell lines showed upregulation of MMP-20 protein and mRNA, respectively, while immunofluorescence showed coexpression of MMP-20 and DSPP. 25666817 14 101 theme oral 2316:2319 arg1 carcinogenesis 2321:2334 oral carcinogenesis 2316:2334 oral carcinogenesis 2316:2334 These novel findings provide the foundation to explore the mechanisms and significance of DSPP-MMP-20 interaction in oral carcinogenesis. 25666817 6 102 theme tissues 1071:1077 arg1 cases 1042:1046 21 cases 1039:1046 21 cases of archived human OSCC tissues 1039:1077 Immunohistochemistry analysis of sections from 21 cases of archived human OSCC tissues showed immunoreactivity for MMP-20 in 18 (86%) and coexpression with DSPP in all 15 cases (71%) positive for DSPP. 25666817 2 103 theme integrin-binding 414:429 arg1 protein 523:529 dentin matrix protein 1 509:531 dentin matrix protein 1 509:531 In biochemical system, MMP-2, MMP-3, and MMP-9 bind with high affinity to, and are activated by, specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs): bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 25666817 2 103 theme integrin-binding 414:429 arg1 glycoproteins 447:459 specific small integrin-binding ligand N-linked glycoproteins 399:459 specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs) 399:470 In biochemical system, MMP-2, MMP-3, and MMP-9 bind with high affinity to, and are activated by, specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs): bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 25666817 2 103 theme integrin-binding 414:429 arg1 sialoprotein 478:489 bone sialoprotein 473:489 bone sialoprotein 473:489 In biochemical system, MMP-2, MMP-3, and MMP-9 bind with high affinity to, and are activated by, specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs): bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 25666817 2 103 theme integrin-binding 414:429 arg1 SIBLINGs 462:469 SIBLINGs 462:469 SIBLINGs 462:469 In biochemical system, MMP-2, MMP-3, and MMP-9 bind with high affinity to, and are activated by, specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs): bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 25666817 2 103 theme integrin-binding 414:429 arg1 osteopontin 492:502 osteopontin 492:502 osteopontin 492:502 In biochemical system, MMP-2, MMP-3, and MMP-9 bind with high affinity to, and are activated by, specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs): bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 25666817 8 104 theme DSPP 1496:1499 arg1 coexpression 1469:1480 coexpression 1469:1480 coexpression of MMP-20 and DSPP 1469:1499 Western blot and quantitative real-time polymerase chain reaction analysis on OSCC cell lines showed upregulation of MMP-20 protein and mRNA, respectively, while immunofluorescence showed coexpression of MMP-20 and DSPP. 25666817 6 105 from coexpression 1130:1141 arg1 % 1172:1172 71% 1170:1172 71% 1170:1172 Immunohistochemistry analysis of sections from 21 cases of archived human OSCC tissues showed immunoreactivity for MMP-20 in 18 (86%) and coexpression with DSPP in all 15 cases (71%) positive for DSPP. 25666817 6 105 from coexpression 1130:1141 arg1 18 1117:1118 18 1117:1118 18 1117:1118 Immunohistochemistry analysis of sections from 21 cases of archived human OSCC tissues showed immunoreactivity for MMP-20 in 18 (86%) and coexpression with DSPP in all 15 cases (71%) positive for DSPP. 25666817 6 105 from coexpression 1130:1141 arg1 % 1123:1123 86% 1121:1123 86% 1121:1123 Immunohistochemistry analysis of sections from 21 cases of archived human OSCC tissues showed immunoreactivity for MMP-20 in 18 (86%) and coexpression with DSPP in all 15 cases (71%) positive for DSPP. 25666817 6 105 from coexpression 1130:1141 arg1 cases 1163:1167 all 15 cases 1156:1167 all 15 cases (71%) positive for DSPP 1156:1191 Immunohistochemistry analysis of sections from 21 cases of archived human OSCC tissues showed immunoreactivity for MMP-20 in 18 (86%) and coexpression with DSPP in all 15 cases (71%) positive for DSPP. 25666817 0 106 theme sialophosphoprotein 35:53 arg1 interaction 55:65 sialophosphoprotein interaction 35:65 sialophosphoprotein interaction in oral cancer 35:80 Matrix metalloproteinase 20-dentin sialophosphoprotein interaction in oral cancer. 25666817 5 107 theme oral 953:956 arg1 carcinomas 972:981 oral squamous cell carcinomas 953:981 oral squamous cell carcinomas (OSCCs) 953:989 Our goal was to investigate MMP-20 expression and to explore preliminary evidence of its interaction with DSPP in oral squamous cell carcinomas (OSCCs). 25666817 5 107 theme oral 953:956 arg1 OSCCs 984:988 OSCCs 984:988 OSCCs 984:988 Our goal was to investigate MMP-20 expression and to explore preliminary evidence of its interaction with DSPP in oral squamous cell carcinomas (OSCCs). 25666817 10 108 theme 9-fold 1806:1811 arg1 enrichment 1813:1822 a 9-fold enrichment 1804:1822 a 9-fold enrichment of DSPP at MMP-20 promoter-proximal elements 1804:1867 Significantly, results of chromatin immunoprecipation revealed a 9-fold enrichment of DSPP at MMP-20 promoter-proximal elements. 25666817 6 109 theme human 1060:1064 arg1 tissues 1071:1077 archived human OSCC tissues 1051:1077 archived human OSCC tissues 1051:1077 Immunohistochemistry analysis of sections from 21 cases of archived human OSCC tissues showed immunoreactivity for MMP-20 in 18 (86%) and coexpression with DSPP in all 15 cases (71%) positive for DSPP. 25666817 2 110 theme specific 399:406 arg1 protein 523:529 dentin matrix protein 1 509:531 dentin matrix protein 1 509:531 In biochemical system, MMP-2, MMP-3, and MMP-9 bind with high affinity to, and are activated by, specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs): bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 25666817 2 110 theme specific 399:406 arg1 glycoproteins 447:459 specific small integrin-binding ligand N-linked glycoproteins 399:459 specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs) 399:470 In biochemical system, MMP-2, MMP-3, and MMP-9 bind with high affinity to, and are activated by, specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs): bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 25666817 2 110 theme specific 399:406 arg1 sialoprotein 478:489 bone sialoprotein 473:489 bone sialoprotein 473:489 In biochemical system, MMP-2, MMP-3, and MMP-9 bind with high affinity to, and are activated by, specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs): bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 25666817 2 110 theme specific 399:406 arg1 SIBLINGs 462:469 SIBLINGs 462:469 SIBLINGs 462:469 In biochemical system, MMP-2, MMP-3, and MMP-9 bind with high affinity to, and are activated by, specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs): bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 25666817 2 110 theme specific 399:406 arg1 osteopontin 492:502 osteopontin 492:502 osteopontin 492:502 In biochemical system, MMP-2, MMP-3, and MMP-9 bind with high affinity to, and are activated by, specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs): bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 25666817 8 111 theme quantitative 1298:1309 arg1 reaction 1338:1345 quantitative real-time polymerase chain reaction 1298:1345 quantitative real-time polymerase chain reaction analysis 1298:1354 Western blot and quantitative real-time polymerase chain reaction analysis on OSCC cell lines showed upregulation of MMP-20 protein and mRNA, respectively, while immunofluorescence showed coexpression of MMP-20 and DSPP. 25666817 5 112 from carcinomas 972:981 arg1 evidence 912:919 preliminary evidence 900:919 preliminary evidence of its interaction with DSPP in oral squamous cell carcinomas (OSCCs) 900:989 Our goal was to investigate MMP-20 expression and to explore preliminary evidence of its interaction with DSPP in oral squamous cell carcinomas (OSCCs). 25666817 9 113 theme MMP-20 1546:1551 arg1 Colocalization 1502:1515 Colocalization 1502:1515 Colocalization 1502:1515 Colocalization and potential interaction of MMP-20 with dentin sialoprotein was confirmed by coimmunoprecipitation and mass spectrometry analysis of immunoprecipitation product from OSCC cell lysate, and in situ proximity ligation assays. 25666817 9 113 theme MMP-20 1546:1551 arg1 interaction 1531:1541 potential interaction 1521:1541 potential interaction of MMP-20 with dentin sialoprotein 1521:1576 Colocalization and potential interaction of MMP-20 with dentin sialoprotein was confirmed by coimmunoprecipitation and mass spectrometry analysis of immunoprecipitation product from OSCC cell lysate, and in situ proximity ligation assays. 25666817 10 114 theme promoter-proximal 1842:1858 arg1 elements 1860:1867 MMP-20 promoter-proximal elements 1835:1867 MMP-20 promoter-proximal elements 1835:1867 Significantly, results of chromatin immunoprecipation revealed a 9-fold enrichment of DSPP at MMP-20 promoter-proximal elements. 25666817 8 115 theme polymerase 1321:1330 arg1 reaction 1338:1345 quantitative real-time polymerase chain reaction 1298:1345 quantitative real-time polymerase chain reaction analysis 1298:1354 Western blot and quantitative real-time polymerase chain reaction analysis on OSCC cell lines showed upregulation of MMP-20 protein and mRNA, respectively, while immunofluorescence showed coexpression of MMP-20 and DSPP. 25666817 11 116 theme tissue 1920:1925 arg1 distribution 1927:1938 a wider tissue distribution 1912:1938 a wider tissue distribution than previously acknowledged 1912:1967 Our data provide evidence that MMP-20 has a wider tissue distribution than previously acknowledged. 25666817 9 117 theme dentin 1558:1563 arg1 sialoprotein 1565:1576 dentin sialoprotein 1558:1576 dentin sialoprotein 1558:1576 Colocalization and potential interaction of MMP-20 with dentin sialoprotein was confirmed by coimmunoprecipitation and mass spectrometry analysis of immunoprecipitation product from OSCC cell lysate, and in situ proximity ligation assays. 25666817 2 118 theme N-linked 438:445 arg1 protein 523:529 dentin matrix protein 1 509:531 dentin matrix protein 1 509:531 In biochemical system, MMP-2, MMP-3, and MMP-9 bind with high affinity to, and are activated by, specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs): bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 25666817 2 118 theme N-linked 438:445 arg1 glycoproteins 447:459 specific small integrin-binding ligand N-linked glycoproteins 399:459 specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs) 399:470 In biochemical system, MMP-2, MMP-3, and MMP-9 bind with high affinity to, and are activated by, specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs): bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 25666817 2 118 theme N-linked 438:445 arg1 sialoprotein 478:489 bone sialoprotein 473:489 bone sialoprotein 473:489 In biochemical system, MMP-2, MMP-3, and MMP-9 bind with high affinity to, and are activated by, specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs): bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 25666817 2 118 theme N-linked 438:445 arg1 SIBLINGs 462:469 SIBLINGs 462:469 SIBLINGs 462:469 In biochemical system, MMP-2, MMP-3, and MMP-9 bind with high affinity to, and are activated by, specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs): bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 25666817 2 118 theme N-linked 438:445 arg1 osteopontin 492:502 osteopontin 492:502 osteopontin 492:502 In biochemical system, MMP-2, MMP-3, and MMP-9 bind with high affinity to, and are activated by, specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs): bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 25666817 8 119 theme reaction 1338:1345 arg1 analysis 1347:1354 quantitative real-time polymerase chain reaction analysis 1298:1354 quantitative real-time polymerase chain reaction analysis 1298:1354 Western blot and quantitative real-time polymerase chain reaction analysis on OSCC cell lines showed upregulation of MMP-20 protein and mRNA, respectively, while immunofluorescence showed coexpression of MMP-20 and DSPP. 25666817 4 120 theme matrix 772:777 arg1 phosphogylcoprotein-are 793:815 matrix extracellular phosphogylcoprotein-are 772:815 matrix extracellular phosphogylcoprotein-are 772:815 However, the cognate MMPs for 2 other SIBLINGs-DSPP and matrix extracellular phosphogylcoprotein-are yet to be identified. 25666817 1 121 theme dentin 233:238 arg1 sialoprotein 240:251 dentin sialoprotein 233:251 dentin sialoprotein 233:251 Matrix metalloproteinase 20 (MMP-20), widely regarded as tooth specific, participates with MMP-2 in processing dentin sialophosphoprotein (DSPP) into dentin sialoprotein, dentin phosphoprotein, and dentin glycoprotein. 25666817 9 122 from assays 1733:1738 arg1 analysis 1639:1646 mass spectrometry analysis 1621:1646 mass spectrometry analysis of immunoprecipitation product from OSCC cell lysate, and in situ proximity ligation assays 1621:1738 Colocalization and potential interaction of MMP-20 with dentin sialoprotein was confirmed by coimmunoprecipitation and mass spectrometry analysis of immunoprecipitation product from OSCC cell lysate, and in situ proximity ligation assays. 25666817 9 122 from assays 1733:1738 arg1 product 1671:1677 immunoprecipitation product 1651:1677 immunoprecipitation product from OSCC cell lysate, and in situ proximity ligation assays 1651:1738 Colocalization and potential interaction of MMP-20 with dentin sialoprotein was confirmed by coimmunoprecipitation and mass spectrometry analysis of immunoprecipitation product from OSCC cell lysate, and in situ proximity ligation assays. 25666817 9 122 from assays 1733:1738 arg1 coimmunoprecipitation 1595:1615 coimmunoprecipitation 1595:1615 coimmunoprecipitation 1595:1615 Colocalization and potential interaction of MMP-20 with dentin sialoprotein was confirmed by coimmunoprecipitation and mass spectrometry analysis of immunoprecipitation product from OSCC cell lysate, and in situ proximity ligation assays. 25666817 11 123 dep distribution 1927:1938 arg1 acknowledged 1956:1967 acknowledged 1956:1967 acknowledged 1956:1967 Our data provide evidence that MMP-20 has a wider tissue distribution than previously acknowledged. 25666817 8 124 theme cell 1364:1367 arg1 lines 1369:1373 OSCC cell lines 1359:1373 OSCC cell lines 1359:1373 Western blot and quantitative real-time polymerase chain reaction analysis on OSCC cell lines showed upregulation of MMP-20 protein and mRNA, respectively, while immunofluorescence showed coexpression of MMP-20 and DSPP. 26512709 4 0 theme Env 670:672 arg1 trimer 674:679 the Env trimer 666:679 the Env trimer 666:679 Moreover, BG505 SOSIP.664 enabled elucidation of the atomic resolution structure of the Env trimer and facilitated the isolation and characterization of new broadly neutralizing antibodies against HIV-1. 26512709 1 1 theme envelope 149:156 arg1 Env 172:174 Env 172:174 Env 172:174 Generation of a stable, soluble mimic of the HIV-1 envelope glycoprotein (Env) trimer on the virion surface has been considered an important first step for developing a successful HIV-1 vaccine. 26512709 1 1 theme envelope 149:156 arg1 glycoprotein 158:169 HIV-1 envelope glycoprotein 143:169 the HIV-1 envelope glycoprotein (Env) trimer on the virion surface 139:204 Generation of a stable, soluble mimic of the HIV-1 envelope glycoprotein (Env) trimer on the virion surface has been considered an important first step for developing a successful HIV-1 vaccine. 26512709 1 2 theme important 229:237 arg1 step 245:248 an important first step 226:248 an important first step for developing a successful HIV-1 vaccine 226:290 Generation of a stable, soluble mimic of the HIV-1 envelope glycoprotein (Env) trimer on the virion surface has been considered an important first step for developing a successful HIV-1 vaccine. 26512709 0 3 theme Trimer 90:95 arg1 Characterization 16:31 Characterization 16:31 Characterization 16:31 Engineering and Characterization of a Fluorescent Native-Like HIV-1 Envelope Glycoprotein Trimer. 26512709 0 3 theme Trimer 90:95 arg1 Engineering 0:10 Engineering 0:10 Engineering 0:10 Engineering and Characterization of a Fluorescent Native-Like HIV-1 Envelope Glycoprotein Trimer. 26512709 1 4 theme glycoprotein 158:169 arg1 trimer 177:182 the HIV-1 envelope glycoprotein (Env) trimer 139:182 the HIV-1 envelope glycoprotein (Env) trimer on the virion surface 139:204 Generation of a stable, soluble mimic of the HIV-1 envelope glycoprotein (Env) trimer on the virion surface has been considered an important first step for developing a successful HIV-1 vaccine. 26512709 1 5 theme first 239:243 arg1 step 245:248 an important first step 226:248 an important first step for developing a successful HIV-1 vaccine 226:290 Generation of a stable, soluble mimic of the HIV-1 envelope glycoprotein (Env) trimer on the virion surface has been considered an important first step for developing a successful HIV-1 vaccine. 26512709 3 6 theme consistent 496:505 arg1 antibodies 520:529 consistent neutralizing antibodies 496:529 consistent neutralizing antibodies against a neutralization-resistant (tier 2) virus 496:579 This protein has facilitated major advances in the HIV-1 vaccine field, since it was the first Env immunogen that induced consistent neutralizing antibodies against a neutralization-resistant (tier 2) virus. 26512709 5 7 theme efficient 921:929 arg1 folding 931:937 efficient folding 921:937 efficient folding (BG505 SOSIP.664-sfGFP) 921:961 Here, we designed and characterized the BG505 SOSIP.664 trimer fused to fluorescent superfolder GFP (sfGFP), a GFP variant that allows efficient folding (BG505 SOSIP.664-sfGFP). 26512709 5 7 theme efficient 921:929 arg1 SOSIP.664-sfGFP 946:960 BG505 SOSIP.664-sfGFP 940:960 BG505 SOSIP.664-sfGFP 940:960 Here, we designed and characterized the BG505 SOSIP.664 trimer fused to fluorescent superfolder GFP (sfGFP), a GFP variant that allows efficient folding (BG505 SOSIP.664-sfGFP). 26512709 4 8 theme new 735:737 arg1 antibodies 760:769 new broadly neutralizing antibodies 735:769 new broadly neutralizing antibodies against HIV-1 735:783 Moreover, BG505 SOSIP.664 enabled elucidation of the atomic resolution structure of the Env trimer and facilitated the isolation and characterization of new broadly neutralizing antibodies against HIV-1. 26512709 3 9 theme neutralizing 507:518 arg1 antibodies 520:529 consistent neutralizing antibodies 496:529 consistent neutralizing antibodies against a neutralization-resistant (tier 2) virus 496:579 This protein has facilitated major advances in the HIV-1 vaccine field, since it was the first Env immunogen that induced consistent neutralizing antibodies against a neutralization-resistant (tier 2) virus. 26512709 4 10 dep isolation 701:709 arg1 the 697:699 the 697:699 the 697:699 Moreover, BG505 SOSIP.664 enabled elucidation of the atomic resolution structure of the Env trimer and facilitated the isolation and characterization of new broadly neutralizing antibodies against HIV-1. 26512709 7 11 theme flow 1202:1205 arg1 cytometry 1207:1215 flow cytometry 1202:1215 flow cytometry 1202:1215 In addition, we show that BG505 SOSIP.664-sfGFP can be used for fluorescence-based assays, such as flow cytometry. 26512709 6 12 theme Env 1003:1005 arg1 protein 1007:1013 the Env protein 999:1013 the Env protein 999:1013 Despite the presence of the sfGFP, the Env protein largely retained its morphology, antigenicity, glycan composition, and thermostability. 26512709 4 13 theme antibodies 760:769 arg1 characterization 715:730 characterization 715:730 characterization 715:730 Moreover, BG505 SOSIP.664 enabled elucidation of the atomic resolution structure of the Env trimer and facilitated the isolation and characterization of new broadly neutralizing antibodies against HIV-1. 26512709 4 13 theme antibodies 760:769 arg1 isolation 701:709 isolation 701:709 isolation 701:709 Moreover, BG505 SOSIP.664 enabled elucidation of the atomic resolution structure of the Env trimer and facilitated the isolation and characterization of new broadly neutralizing antibodies against HIV-1. 26512709 4 14 theme neutralizing 747:758 arg1 antibodies 760:769 new broadly neutralizing antibodies 735:769 new broadly neutralizing antibodies against HIV-1 735:783 Moreover, BG505 SOSIP.664 enabled elucidation of the atomic resolution structure of the Env trimer and facilitated the isolation and characterization of new broadly neutralizing antibodies against HIV-1. 26512709 7 15 theme fluorescence-based 1167:1184 arg1 assays 1186:1191 fluorescence-based assays 1167:1191 fluorescence-based assays 1167:1191 In addition, we show that BG505 SOSIP.664-sfGFP can be used for fluorescence-based assays, such as flow cytometry. 26512709 7 16 used used 1158:1161 arg2 SOSIP.664-sfGFP 1135:1149 BG505 SOSIP.664-sfGFP 1129:1149 BG505 SOSIP.664-sfGFP 1129:1149 In addition, we show that BG505 SOSIP.664-sfGFP can be used for fluorescence-based assays, such as flow cytometry. 26512709 4 17 theme resolution 642:651 arg1 structure 653:661 the atomic resolution structure 631:661 the atomic resolution structure of the Env trimer 631:679 Moreover, BG505 SOSIP.664 enabled elucidation of the atomic resolution structure of the Env trimer and facilitated the isolation and characterization of new broadly neutralizing antibodies against HIV-1. 26512709 7 18 theme BG505 1129:1133 arg1 SOSIP.664-sfGFP 1135:1149 BG505 SOSIP.664-sfGFP 1129:1149 BG505 SOSIP.664-sfGFP 1129:1149 In addition, we show that BG505 SOSIP.664-sfGFP can be used for fluorescence-based assays, such as flow cytometry. 26512709 3 19 theme neutralization-resistant 541:564 arg1 virus 575:579 a neutralization-resistant (tier 2) virus 539:579 a neutralization-resistant (tier 2) virus 539:579 This protein has facilitated major advances in the HIV-1 vaccine field, since it was the first Env immunogen that induced consistent neutralizing antibodies against a neutralization-resistant (tier 2) virus. 26512709 3 20 theme major 403:407 arg1 advances 409:416 major advances 403:416 major advances in the HIV-1 vaccine field 403:443 This protein has facilitated major advances in the HIV-1 vaccine field, since it was the first Env immunogen that induced consistent neutralizing antibodies against a neutralization-resistant (tier 2) virus. 26512709 5 21 theme GFP 897:899 arg1 variant 901:907 a GFP variant 895:907 a GFP variant that allows efficient folding (BG505 SOSIP.664-sfGFP) 895:961 Here, we designed and characterized the BG505 SOSIP.664 trimer fused to fluorescent superfolder GFP (sfGFP), a GFP variant that allows efficient folding (BG505 SOSIP.664-sfGFP). 26512709 5 21 theme GFP 897:899 arg1 GFP 882:884 fluorescent superfolder GFP 858:884 fluorescent superfolder GFP (sfGFP) 858:892 Here, we designed and characterized the BG505 SOSIP.664 trimer fused to fluorescent superfolder GFP (sfGFP), a GFP variant that allows efficient folding (BG505 SOSIP.664-sfGFP). 26512709 3 22 theme vaccine 431:437 arg1 field 439:443 the HIV-1 vaccine field 421:443 the HIV-1 vaccine field 421:443 This protein has facilitated major advances in the HIV-1 vaccine field, since it was the first Env immunogen that induced consistent neutralizing antibodies against a neutralization-resistant (tier 2) virus. 26512709 1 23 theme successful 267:276 arg1 vaccine 284:290 a successful HIV-1 vaccine 265:290 a successful HIV-1 vaccine 265:290 Generation of a stable, soluble mimic of the HIV-1 envelope glycoprotein (Env) trimer on the virion surface has been considered an important first step for developing a successful HIV-1 vaccine. 26512709 3 24 theme first 463:467 arg1 it 452:453 it 452:453 it 452:453 This protein has facilitated major advances in the HIV-1 vaccine field, since it was the first Env immunogen that induced consistent neutralizing antibodies against a neutralization-resistant (tier 2) virus. 26512709 3 24 theme first 463:467 arg1 immunogen 473:481 the first Env immunogen 459:481 the first Env immunogen that induced consistent neutralizing antibodies against a neutralization-resistant (tier 2) virus 459:579 This protein has facilitated major advances in the HIV-1 vaccine field, since it was the first Env immunogen that induced consistent neutralizing antibodies against a neutralization-resistant (tier 2) virus. 26512709 3 25 dep neutralization-resistant 541:564 arg1 tier 567:570 tier 2 567:572 tier 2 567:572 This protein has facilitated major advances in the HIV-1 vaccine field, since it was the first Env immunogen that induced consistent neutralizing antibodies against a neutralization-resistant (tier 2) virus. 26512709 5 26 theme superfolder 870:880 arg1 variant 901:907 a GFP variant 895:907 a GFP variant that allows efficient folding (BG505 SOSIP.664-sfGFP) 895:961 Here, we designed and characterized the BG505 SOSIP.664 trimer fused to fluorescent superfolder GFP (sfGFP), a GFP variant that allows efficient folding (BG505 SOSIP.664-sfGFP). 26512709 5 26 theme superfolder 870:880 arg1 sfGFP 887:891 sfGFP 887:891 sfGFP 887:891 Here, we designed and characterized the BG505 SOSIP.664 trimer fused to fluorescent superfolder GFP (sfGFP), a GFP variant that allows efficient folding (BG505 SOSIP.664-sfGFP). 26512709 5 26 theme superfolder 870:880 arg1 GFP 882:884 fluorescent superfolder GFP 858:884 fluorescent superfolder GFP (sfGFP) 858:892 Here, we designed and characterized the BG505 SOSIP.664 trimer fused to fluorescent superfolder GFP (sfGFP), a GFP variant that allows efficient folding (BG505 SOSIP.664-sfGFP). 26512709 0 27 theme Fluorescent 38:48 arg1 Trimer 90:95 a Fluorescent Native-Like HIV-1 Envelope Glycoprotein Trimer 36:95 a Fluorescent Native-Like HIV-1 Envelope Glycoprotein Trimer 36:95 Engineering and Characterization of a Fluorescent Native-Like HIV-1 Envelope Glycoprotein Trimer. 26512709 1 28 theme HIV-1 278:282 arg1 vaccine 284:290 a successful HIV-1 vaccine 265:290 a successful HIV-1 vaccine 265:290 Generation of a stable, soluble mimic of the HIV-1 envelope glycoprotein (Env) trimer on the virion surface has been considered an important first step for developing a successful HIV-1 vaccine. 26512709 5 29 theme BG505 826:830 arg1 trimer 842:847 the BG505 SOSIP.664 trimer 822:847 the BG505 SOSIP.664 trimer fused to fluorescent superfolder GFP (sfGFP), a GFP variant that allows efficient folding (BG505 SOSIP.664-sfGFP) 822:961 Here, we designed and characterized the BG505 SOSIP.664 trimer fused to fluorescent superfolder GFP (sfGFP), a GFP variant that allows efficient folding (BG505 SOSIP.664-sfGFP). 26512709 4 30 theme atomic 635:640 arg1 structure 653:661 the atomic resolution structure 631:661 the atomic resolution structure of the Env trimer 631:679 Moreover, BG505 SOSIP.664 enabled elucidation of the atomic resolution structure of the Env trimer and facilitated the isolation and characterization of new broadly neutralizing antibodies against HIV-1. 26512709 1 31 theme virion 191:196 arg1 surface 198:204 the virion surface 187:204 the virion surface 187:204 Generation of a stable, soluble mimic of the HIV-1 envelope glycoprotein (Env) trimer on the virion surface has been considered an important first step for developing a successful HIV-1 vaccine. 26512709 3 32 theme HIV-1 425:429 arg1 field 439:443 the HIV-1 vaccine field 421:443 the HIV-1 vaccine field 421:443 This protein has facilitated major advances in the HIV-1 vaccine field, since it was the first Env immunogen that induced consistent neutralizing antibodies against a neutralization-resistant (tier 2) virus. 26512709 0 33 theme HIV-1 62:66 arg1 Trimer 90:95 a Fluorescent Native-Like HIV-1 Envelope Glycoprotein Trimer 36:95 a Fluorescent Native-Like HIV-1 Envelope Glycoprotein Trimer 36:95 Engineering and Characterization of a Fluorescent Native-Like HIV-1 Envelope Glycoprotein Trimer. 26512709 6 34 theme glycan 1062:1067 arg1 composition 1069:1079 glycan composition 1062:1079 glycan composition 1062:1079 Despite the presence of the sfGFP, the Env protein largely retained its morphology, antigenicity, glycan composition, and thermostability. 26512709 2 35 theme Env 325:327 arg1 trimer 329:334 a soluble native-like Env trimer 303:334 a soluble native-like Env trimer (BG505 SOSIP.664) 303:352 Recently, a soluble native-like Env trimer (BG505 SOSIP.664) has been described. 26512709 2 35 theme Env 325:327 arg1 SOSIP.664 343:351 BG505 SOSIP.664 337:351 BG505 SOSIP.664 337:351 Recently, a soluble native-like Env trimer (BG505 SOSIP.664) has been described. 26512709 0 36 theme Native-Like 50:60 arg1 Trimer 90:95 a Fluorescent Native-Like HIV-1 Envelope Glycoprotein Trimer 36:95 a Fluorescent Native-Like HIV-1 Envelope Glycoprotein Trimer 36:95 Engineering and Characterization of a Fluorescent Native-Like HIV-1 Envelope Glycoprotein Trimer. 26512709 2 37 theme native-like 313:323 arg1 trimer 329:334 a soluble native-like Env trimer 303:334 a soluble native-like Env trimer (BG505 SOSIP.664) 303:352 Recently, a soluble native-like Env trimer (BG505 SOSIP.664) has been described. 26512709 2 37 theme native-like 313:323 arg1 SOSIP.664 343:351 BG505 SOSIP.664 337:351 BG505 SOSIP.664 337:351 Recently, a soluble native-like Env trimer (BG505 SOSIP.664) has been described. 26512709 1 38 gly glycoprotein 158:169 arg1 Env 172:174 Env 172:174 Env 172:174 Generation of a stable, soluble mimic of the HIV-1 envelope glycoprotein (Env) trimer on the virion surface has been considered an important first step for developing a successful HIV-1 vaccine. 26512709 1 38 gly glycoprotein 158:169 arg1 glycoprotein 158:169 HIV-1 envelope glycoprotein 143:169 the HIV-1 envelope glycoprotein (Env) trimer on the virion surface 139:204 Generation of a stable, soluble mimic of the HIV-1 envelope glycoprotein (Env) trimer on the virion surface has been considered an important first step for developing a successful HIV-1 vaccine. 26512709 4 39 theme structure 653:661 arg1 elucidation 616:626 elucidation 616:626 elucidation of the atomic resolution structure of the Env trimer 616:679 Moreover, BG505 SOSIP.664 enabled elucidation of the atomic resolution structure of the Env trimer and facilitated the isolation and characterization of new broadly neutralizing antibodies against HIV-1. 26512709 1 40 theme mimic 130:134 arg1 Generation 98:107 Generation 98:107 Generation of a stable, soluble mimic of the HIV-1 envelope glycoprotein (Env) trimer on the virion surface 98:204 Generation of a stable, soluble mimic of the HIV-1 envelope glycoprotein (Env) trimer on the virion surface has been considered an important first step for developing a successful HIV-1 vaccine. 26512709 5 41 theme fluorescent 858:868 arg1 variant 901:907 a GFP variant 895:907 a GFP variant that allows efficient folding (BG505 SOSIP.664-sfGFP) 895:961 Here, we designed and characterized the BG505 SOSIP.664 trimer fused to fluorescent superfolder GFP (sfGFP), a GFP variant that allows efficient folding (BG505 SOSIP.664-sfGFP). 26512709 5 41 theme fluorescent 858:868 arg1 sfGFP 887:891 sfGFP 887:891 sfGFP 887:891 Here, we designed and characterized the BG505 SOSIP.664 trimer fused to fluorescent superfolder GFP (sfGFP), a GFP variant that allows efficient folding (BG505 SOSIP.664-sfGFP). 26512709 5 41 theme fluorescent 858:868 arg1 GFP 882:884 fluorescent superfolder GFP 858:884 fluorescent superfolder GFP (sfGFP) 858:892 Here, we designed and characterized the BG505 SOSIP.664 trimer fused to fluorescent superfolder GFP (sfGFP), a GFP variant that allows efficient folding (BG505 SOSIP.664-sfGFP). 26512709 6 42 theme sfGFP 992:996 arg1 presence 976:983 the presence 972:983 the presence of the sfGFP 972:996 Despite the presence of the sfGFP, the Env protein largely retained its morphology, antigenicity, glycan composition, and thermostability. 26512709 4 43 theme broadly 739:745 arg1 antibodies 760:769 new broadly neutralizing antibodies 735:769 new broadly neutralizing antibodies against HIV-1 735:783 Moreover, BG505 SOSIP.664 enabled elucidation of the atomic resolution structure of the Env trimer and facilitated the isolation and characterization of new broadly neutralizing antibodies against HIV-1. 26512709 1 44 theme HIV-1 143:147 arg1 Env 172:174 Env 172:174 Env 172:174 Generation of a stable, soluble mimic of the HIV-1 envelope glycoprotein (Env) trimer on the virion surface has been considered an important first step for developing a successful HIV-1 vaccine. 26512709 1 44 theme HIV-1 143:147 arg1 glycoprotein 158:169 HIV-1 envelope glycoprotein 143:169 the HIV-1 envelope glycoprotein (Env) trimer on the virion surface 139:204 Generation of a stable, soluble mimic of the HIV-1 envelope glycoprotein (Env) trimer on the virion surface has been considered an important first step for developing a successful HIV-1 vaccine. 26512709 2 45 theme soluble 305:311 arg1 trimer 329:334 a soluble native-like Env trimer 303:334 a soluble native-like Env trimer (BG505 SOSIP.664) 303:352 Recently, a soluble native-like Env trimer (BG505 SOSIP.664) has been described. 26512709 2 45 theme soluble 305:311 arg1 SOSIP.664 343:351 BG505 SOSIP.664 337:351 BG505 SOSIP.664 337:351 Recently, a soluble native-like Env trimer (BG505 SOSIP.664) has been described. 26512709 0 46 theme Glycoprotein 77:88 arg1 Trimer 90:95 a Fluorescent Native-Like HIV-1 Envelope Glycoprotein Trimer 36:95 a Fluorescent Native-Like HIV-1 Envelope Glycoprotein Trimer 36:95 Engineering and Characterization of a Fluorescent Native-Like HIV-1 Envelope Glycoprotein Trimer. 26512709 5 47 theme SOSIP.664 832:840 arg1 trimer 842:847 the BG505 SOSIP.664 trimer 822:847 the BG505 SOSIP.664 trimer fused to fluorescent superfolder GFP (sfGFP), a GFP variant that allows efficient folding (BG505 SOSIP.664-sfGFP) 822:961 Here, we designed and characterized the BG505 SOSIP.664 trimer fused to fluorescent superfolder GFP (sfGFP), a GFP variant that allows efficient folding (BG505 SOSIP.664-sfGFP). 26512709 1 48 from trimer 177:182 arg1 surface 198:204 the virion surface 187:204 the virion surface 187:204 Generation of a stable, soluble mimic of the HIV-1 envelope glycoprotein (Env) trimer on the virion surface has been considered an important first step for developing a successful HIV-1 vaccine. 26512709 3 49 theme Env 469:471 arg1 it 452:453 it 452:453 it 452:453 This protein has facilitated major advances in the HIV-1 vaccine field, since it was the first Env immunogen that induced consistent neutralizing antibodies against a neutralization-resistant (tier 2) virus. 26512709 3 49 theme Env 469:471 arg1 immunogen 473:481 the first Env immunogen 459:481 the first Env immunogen that induced consistent neutralizing antibodies against a neutralization-resistant (tier 2) virus 459:579 This protein has facilitated major advances in the HIV-1 vaccine field, since it was the first Env immunogen that induced consistent neutralizing antibodies against a neutralization-resistant (tier 2) virus. 26512709 0 50 theme Envelope 68:75 arg1 Trimer 90:95 a Fluorescent Native-Like HIV-1 Envelope Glycoprotein Trimer 36:95 a Fluorescent Native-Like HIV-1 Envelope Glycoprotein Trimer 36:95 Engineering and Characterization of a Fluorescent Native-Like HIV-1 Envelope Glycoprotein Trimer. 26512709 3 51 from advances 409:416 arg1 field 439:443 the HIV-1 vaccine field 421:443 the HIV-1 vaccine field 421:443 This protein has facilitated major advances in the HIV-1 vaccine field, since it was the first Env immunogen that induced consistent neutralizing antibodies against a neutralization-resistant (tier 2) virus. 26512709 1 52 dep stable 114:119 arg1 soluble 122:128 soluble 122:128 soluble 122:128 Generation of a stable, soluble mimic of the HIV-1 envelope glycoprotein (Env) trimer on the virion surface has been considered an important first step for developing a successful HIV-1 vaccine. 26512709 4 53 theme trimer 674:679 arg1 structure 653:661 the atomic resolution structure 631:661 the atomic resolution structure of the Env trimer 631:679 Moreover, BG505 SOSIP.664 enabled elucidation of the atomic resolution structure of the Env trimer and facilitated the isolation and characterization of new broadly neutralizing antibodies against HIV-1. 28814986 0 0 theme N-Linked 105:112 arg1 Glycosylation 114:126 N-Linked Glycosylation 105:126 N-Linked Glycosylation 105:126 2-Deoxy-D-glucose Restore Glucocorticoid Sensitivity in Acute Lymphoblastic Leukemia via Modification of N-Linked Glycosylation in an Oxygen Tension-Independent Manner. 28814986 6 1 theme glucose 1157:1163 arg1 analog 1165:1170 the glucose analog 1153:1170 the glucose analog 1153:1170 We demonstrate a hexokinase II-independent cell viability decrease and apoptosis induction of the glucose analog in leukemia. 28814986 1 2 theme lymphoblastic 188:200 arg1 leukemia 202:209 childhood acute lymphoblastic leukemia 172:209 childhood acute lymphoblastic leukemia 172:209 In childhood acute lymphoblastic leukemia, treatment failure is associated with resistance to glucocorticoid agents. 28814986 6 3 theme viability 1107:1115 arg1 decrease 1117:1124 a hexokinase II-independent cell viability decrease 1074:1124 a hexokinase II-independent cell viability decrease 1074:1124 We demonstrate a hexokinase II-independent cell viability decrease and apoptosis induction of the glucose analog in leukemia. 28814986 6 4 theme analog 1165:1170 arg1 decrease 1117:1124 a hexokinase II-independent cell viability decrease 1074:1124 a hexokinase II-independent cell viability decrease 1074:1124 We demonstrate a hexokinase II-independent cell viability decrease and apoptosis induction of the glucose analog in leukemia. 28814986 6 4 theme analog 1165:1170 arg1 induction 1140:1148 apoptosis induction 1130:1148 apoptosis induction of the glucose analog in leukemia 1130:1182 We demonstrate a hexokinase II-independent cell viability decrease and apoptosis induction of the glucose analog in leukemia. 28814986 6 5 from decrease 1117:1124 arg1 leukemia 1175:1182 leukemia 1175:1182 leukemia 1175:1182 We demonstrate a hexokinase II-independent cell viability decrease and apoptosis induction of the glucose analog in leukemia. 28814986 6 6 theme cell 1102:1105 arg1 viability 1107:1115 hexokinase II-independent cell viability 1076:1115 a hexokinase II-independent cell viability decrease 1074:1124 We demonstrate a hexokinase II-independent cell viability decrease and apoptosis induction of the glucose analog in leukemia. 28814986 6 7 from induction 1140:1148 arg1 leukemia 1175:1182 leukemia 1175:1182 leukemia 1175:1182 We demonstrate a hexokinase II-independent cell viability decrease and apoptosis induction of the glucose analog in leukemia. 28814986 7 8 theme reticulum 1431:1439 arg1 stress 1441:1446 endoplasmic reticulum stress 1419:1446 endoplasmic reticulum stress 1419:1446 Additionally, due to the structural similarity of 2-deoxy-D-glucose with mannose, we could confirm that the mechanism by which 2-deoxy-D-glucose predominantly acts in leukemia is via modification in N-linked glycosylation, leading to endoplasmic reticulum stress and consequently induction of the unfolded protein response. 28814986 6 9 theme II-independent 1087:1100 arg1 viability 1107:1115 hexokinase II-independent cell viability 1076:1115 a hexokinase II-independent cell viability decrease 1074:1124 We demonstrate a hexokinase II-independent cell viability decrease and apoptosis induction of the glucose analog in leukemia. 28814986 0 10 theme Glycosylation 114:126 arg1 Modification 89:100 Modification 89:100 Modification of N-Linked Glycosylation 89:126 2-Deoxy-D-glucose Restore Glucocorticoid Sensitivity in Acute Lymphoblastic Leukemia via Modification of N-Linked Glycosylation in an Oxygen Tension-Independent Manner. 28814986 6 11 theme hexokinase 1076:1085 arg1 viability 1107:1115 hexokinase II-independent cell viability 1076:1115 a hexokinase II-independent cell viability decrease 1074:1124 We demonstrate a hexokinase II-independent cell viability decrease and apoptosis induction of the glucose analog in leukemia. 28814986 7 12 from modification 1368:1379 arg1 glycosylation 1393:1405 N-linked glycosylation 1384:1405 N-linked glycosylation 1384:1405 Additionally, due to the structural similarity of 2-deoxy-D-glucose with mannose, we could confirm that the mechanism by which 2-deoxy-D-glucose predominantly acts in leukemia is via modification in N-linked glycosylation, leading to endoplasmic reticulum stress and consequently induction of the unfolded protein response. 28814986 5 13 theme antileukemic 983:994 arg1 effects 996:1002 the antileukemic effects 979:1002 the antileukemic effects of 2-deoxy-D-glucose 979:1023 Unlike solid tumors, where 2-deoxy-D-glucose promotes inhibition of glycolysis by hexokinase II exclusively under hypoxic conditions, we were able to show that the antileukemic effects of 2-deoxy-D-glucose are far more complex in leukemia. 28814986 5 13 theme antileukemic 983:994 arg1 complex 1038:1044 complex 1038:1044 complex 1038:1044 Unlike solid tumors, where 2-deoxy-D-glucose promotes inhibition of glycolysis by hexokinase II exclusively under hypoxic conditions, we were able to show that the antileukemic effects of 2-deoxy-D-glucose are far more complex in leukemia. 28814986 4 14 theme tension-independent 791:809 arg1 manner 811:816 an oxygen tension-independent manner 781:816 an oxygen tension-independent manner 781:816 Interestingly, a combinatorial treatment of glucocorticoid and the glucose analog 2-deoxy-D-glucose displayed a synergistic effect in methylprednisolone-resistant cells, in an oxygen tension-independent manner. 28814986 0 15 theme Oxygen 134:139 arg1 Manner 161:166 an Oxygen Tension-Independent Manner 131:166 an Oxygen Tension-Independent Manner 131:166 2-Deoxy-D-glucose Restore Glucocorticoid Sensitivity in Acute Lymphoblastic Leukemia via Modification of N-Linked Glycosylation in an Oxygen Tension-Independent Manner. 28814986 4 16 theme glucose 675:681 arg1 2-deoxy-D-glucose 690:706 the glucose analog 2-deoxy-D-glucose 671:706 the glucose analog 2-deoxy-D-glucose 671:706 Interestingly, a combinatorial treatment of glucocorticoid and the glucose analog 2-deoxy-D-glucose displayed a synergistic effect in methylprednisolone-resistant cells, in an oxygen tension-independent manner. 28814986 4 17 theme synergistic 720:730 arg1 effect 732:737 a synergistic effect 718:737 a synergistic effect 718:737 Interestingly, a combinatorial treatment of glucocorticoid and the glucose analog 2-deoxy-D-glucose displayed a synergistic effect in methylprednisolone-resistant cells, in an oxygen tension-independent manner. 28814986 4 18 theme combinatorial 625:637 arg1 treatment 639:647 a combinatorial treatment 623:647 a combinatorial treatment of glucocorticoid 623:665 Interestingly, a combinatorial treatment of glucocorticoid and the glucose analog 2-deoxy-D-glucose displayed a synergistic effect in methylprednisolone-resistant cells, in an oxygen tension-independent manner. 28814986 2 19 theme drugs 314:318 arg1 class 305:309 this class 300:309 this class of drugs 300:318 Resistance to this class of drugs represents one of the strongest indicators of poor clinical outcome. 28814986 4 20 theme glucocorticoid 652:665 arg1 2-deoxy-D-glucose 690:706 the glucose analog 2-deoxy-D-glucose 671:706 the glucose analog 2-deoxy-D-glucose 671:706 Interestingly, a combinatorial treatment of glucocorticoid and the glucose analog 2-deoxy-D-glucose displayed a synergistic effect in methylprednisolone-resistant cells, in an oxygen tension-independent manner. 28814986 4 20 theme glucocorticoid 652:665 arg1 treatment 639:647 a combinatorial treatment 623:647 a combinatorial treatment of glucocorticoid 623:665 Interestingly, a combinatorial treatment of glucocorticoid and the glucose analog 2-deoxy-D-glucose displayed a synergistic effect in methylprednisolone-resistant cells, in an oxygen tension-independent manner. 28814986 1 21 theme treatment 212:220 arg1 failure 222:228 treatment failure 212:228 treatment failure 212:228 In childhood acute lymphoblastic leukemia, treatment failure is associated with resistance to glucocorticoid agents. 28814986 3 22 theme pathways 564:571 arg1 deregulation 538:549 a deregulation 536:549 a deregulation of metabolic pathways 536:571 We show that leukemic cells, which are resistant to the glucocorticoid drug methylprednisolone, display a higher demand of glucose associated with a deregulation of metabolic pathways, in comparison to sensitive cells. 28814986 3 23 theme drug 460:463 arg1 methylprednisolone 465:482 the glucocorticoid drug methylprednisolone 441:482 the glucocorticoid drug methylprednisolone 441:482 We show that leukemic cells, which are resistant to the glucocorticoid drug methylprednisolone, display a higher demand of glucose associated with a deregulation of metabolic pathways, in comparison to sensitive cells. 28814986 6 24 theme apoptosis 1130:1138 arg1 induction 1140:1148 apoptosis induction 1130:1148 apoptosis induction of the glucose analog in leukemia 1130:1182 We demonstrate a hexokinase II-independent cell viability decrease and apoptosis induction of the glucose analog in leukemia. 28814986 2 25 theme indicators 352:361 arg1 one 331:333 one 331:333 one 331:333 Resistance to this class of drugs represents one of the strongest indicators of poor clinical outcome. 28814986 2 25 theme indicators 352:361 arg1 indicators 352:361 the strongest indicators 338:361 the strongest indicators of poor clinical outcome 338:386 Resistance to this class of drugs represents one of the strongest indicators of poor clinical outcome. 28814986 7 26 theme endoplasmic 1419:1429 arg1 stress 1441:1446 endoplasmic reticulum stress 1419:1446 endoplasmic reticulum stress 1419:1446 Additionally, due to the structural similarity of 2-deoxy-D-glucose with mannose, we could confirm that the mechanism by which 2-deoxy-D-glucose predominantly acts in leukemia is via modification in N-linked glycosylation, leading to endoplasmic reticulum stress and consequently induction of the unfolded protein response. 28814986 7 27 theme 2-deoxy-D-glucose 1235:1251 arg1 similarity 1221:1230 the structural similarity 1206:1230 the structural similarity of 2-deoxy-D-glucose with mannose 1206:1264 Additionally, due to the structural similarity of 2-deoxy-D-glucose with mannose, we could confirm that the mechanism by which 2-deoxy-D-glucose predominantly acts in leukemia is via modification in N-linked glycosylation, leading to endoplasmic reticulum stress and consequently induction of the unfolded protein response. 28814986 2 28 theme strongest 342:350 arg1 indicators 352:361 the strongest indicators 338:361 the strongest indicators of poor clinical outcome 338:386 Resistance to this class of drugs represents one of the strongest indicators of poor clinical outcome. 28814986 4 29 theme analog 683:688 arg1 2-deoxy-D-glucose 690:706 the glucose analog 2-deoxy-D-glucose 671:706 the glucose analog 2-deoxy-D-glucose 671:706 Interestingly, a combinatorial treatment of glucocorticoid and the glucose analog 2-deoxy-D-glucose displayed a synergistic effect in methylprednisolone-resistant cells, in an oxygen tension-independent manner. 28814986 0 30 theme Glucocorticoid 26:39 arg1 Sensitivity 41:51 Glucocorticoid Sensitivity 26:51 Glucocorticoid Sensitivity in Acute Lymphoblastic Leukemia 26:83 2-Deoxy-D-glucose Restore Glucocorticoid Sensitivity in Acute Lymphoblastic Leukemia via Modification of N-Linked Glycosylation in an Oxygen Tension-Independent Manner. 28814986 0 31 theme Tension-Independent 141:159 arg1 Manner 161:166 an Oxygen Tension-Independent Manner 131:166 an Oxygen Tension-Independent Manner 131:166 2-Deoxy-D-glucose Restore Glucocorticoid Sensitivity in Acute Lymphoblastic Leukemia via Modification of N-Linked Glycosylation in an Oxygen Tension-Independent Manner. 28814986 3 32 theme metabolic 554:562 arg1 pathways 564:571 metabolic pathways 554:571 metabolic pathways 554:571 We show that leukemic cells, which are resistant to the glucocorticoid drug methylprednisolone, display a higher demand of glucose associated with a deregulation of metabolic pathways, in comparison to sensitive cells. 28814986 0 33 theme Acute 56:60 arg1 Leukemia 76:83 Acute Lymphoblastic Leukemia 56:83 Acute Lymphoblastic Leukemia 56:83 2-Deoxy-D-glucose Restore Glucocorticoid Sensitivity in Acute Lymphoblastic Leukemia via Modification of N-Linked Glycosylation in an Oxygen Tension-Independent Manner. 28814986 5 34 theme 2-deoxy-D-glucose 1007:1023 arg1 effects 996:1002 the antileukemic effects 979:1002 the antileukemic effects of 2-deoxy-D-glucose 979:1023 Unlike solid tumors, where 2-deoxy-D-glucose promotes inhibition of glycolysis by hexokinase II exclusively under hypoxic conditions, we were able to show that the antileukemic effects of 2-deoxy-D-glucose are far more complex in leukemia. 28814986 5 34 theme 2-deoxy-D-glucose 1007:1023 arg1 complex 1038:1044 complex 1038:1044 complex 1038:1044 Unlike solid tumors, where 2-deoxy-D-glucose promotes inhibition of glycolysis by hexokinase II exclusively under hypoxic conditions, we were able to show that the antileukemic effects of 2-deoxy-D-glucose are far more complex in leukemia. 28814986 5 35 from complex 1038:1044 arg1 leukemia 1049:1056 leukemia 1049:1056 leukemia 1049:1056 Unlike solid tumors, where 2-deoxy-D-glucose promotes inhibition of glycolysis by hexokinase II exclusively under hypoxic conditions, we were able to show that the antileukemic effects of 2-deoxy-D-glucose are far more complex in leukemia. 28814986 3 36 theme glucocorticoid 445:458 arg1 methylprednisolone 465:482 the glucocorticoid drug methylprednisolone 441:482 the glucocorticoid drug methylprednisolone 441:482 We show that leukemic cells, which are resistant to the glucocorticoid drug methylprednisolone, display a higher demand of glucose associated with a deregulation of metabolic pathways, in comparison to sensitive cells. 28814986 3 37 theme higher 495:500 arg1 demand 502:507 a higher demand 493:507 a higher demand of glucose associated with a deregulation of metabolic pathways 493:571 We show that leukemic cells, which are resistant to the glucocorticoid drug methylprednisolone, display a higher demand of glucose associated with a deregulation of metabolic pathways, in comparison to sensitive cells. 28814986 5 38 theme glycolysis 887:896 arg1 inhibition 873:882 inhibition 873:882 inhibition of glycolysis by hexokinase II 873:913 Unlike solid tumors, where 2-deoxy-D-glucose promotes inhibition of glycolysis by hexokinase II exclusively under hypoxic conditions, we were able to show that the antileukemic effects of 2-deoxy-D-glucose are far more complex in leukemia. 28814986 7 39 link N-linked 1384:1391 arg1 glycosylation 1393:1405 N-linked glycosylation 1384:1405 N-linked glycosylation 1384:1405 Additionally, due to the structural similarity of 2-deoxy-D-glucose with mannose, we could confirm that the mechanism by which 2-deoxy-D-glucose predominantly acts in leukemia is via modification in N-linked glycosylation, leading to endoplasmic reticulum stress and consequently induction of the unfolded protein response. 28814986 4 40 theme oxygen 784:789 arg1 manner 811:816 an oxygen tension-independent manner 781:816 an oxygen tension-independent manner 781:816 Interestingly, a combinatorial treatment of glucocorticoid and the glucose analog 2-deoxy-D-glucose displayed a synergistic effect in methylprednisolone-resistant cells, in an oxygen tension-independent manner. 28814986 0 41 theme Lymphoblastic 62:74 arg1 Leukemia 76:83 Acute Lymphoblastic Leukemia 56:83 Acute Lymphoblastic Leukemia 56:83 2-Deoxy-D-glucose Restore Glucocorticoid Sensitivity in Acute Lymphoblastic Leukemia via Modification of N-Linked Glycosylation in an Oxygen Tension-Independent Manner. 28814986 2 42 theme outcome 380:386 arg1 indicators 352:361 the strongest indicators 338:361 the strongest indicators of poor clinical outcome 338:386 Resistance to this class of drugs represents one of the strongest indicators of poor clinical outcome. 28814986 7 43 theme protein 1491:1497 arg1 response 1499:1506 the unfolded protein response 1478:1506 the unfolded protein response 1478:1506 Additionally, due to the structural similarity of 2-deoxy-D-glucose with mannose, we could confirm that the mechanism by which 2-deoxy-D-glucose predominantly acts in leukemia is via modification in N-linked glycosylation, leading to endoplasmic reticulum stress and consequently induction of the unfolded protein response. 28814986 4 44 theme methylprednisolone-resistant 742:769 arg1 cells 771:775 methylprednisolone-resistant cells 742:775 methylprednisolone-resistant cells 742:775 Interestingly, a combinatorial treatment of glucocorticoid and the glucose analog 2-deoxy-D-glucose displayed a synergistic effect in methylprednisolone-resistant cells, in an oxygen tension-independent manner. 28814986 2 45 theme clinical 371:378 arg1 outcome 380:386 poor clinical outcome 366:386 poor clinical outcome 366:386 Resistance to this class of drugs represents one of the strongest indicators of poor clinical outcome. 28814986 3 46 theme sensitive 591:599 arg1 cells 601:605 sensitive cells 591:605 sensitive cells 591:605 We show that leukemic cells, which are resistant to the glucocorticoid drug methylprednisolone, display a higher demand of glucose associated with a deregulation of metabolic pathways, in comparison to sensitive cells. 28814986 1 47 theme glucocorticoid 263:276 arg1 agents 278:283 glucocorticoid agents 263:283 glucocorticoid agents 263:283 In childhood acute lymphoblastic leukemia, treatment failure is associated with resistance to glucocorticoid agents. 28814986 7 48 theme response 1499:1506 arg1 stress 1441:1446 endoplasmic reticulum stress 1419:1446 endoplasmic reticulum stress 1419:1446 Additionally, due to the structural similarity of 2-deoxy-D-glucose with mannose, we could confirm that the mechanism by which 2-deoxy-D-glucose predominantly acts in leukemia is via modification in N-linked glycosylation, leading to endoplasmic reticulum stress and consequently induction of the unfolded protein response. 28814986 7 48 theme response 1499:1506 arg1 induction 1465:1473 induction 1465:1473 induction of the unfolded protein response 1465:1506 Additionally, due to the structural similarity of 2-deoxy-D-glucose with mannose, we could confirm that the mechanism by which 2-deoxy-D-glucose predominantly acts in leukemia is via modification in N-linked glycosylation, leading to endoplasmic reticulum stress and consequently induction of the unfolded protein response. 28814986 7 49 theme structural 1210:1219 arg1 similarity 1221:1230 the structural similarity 1206:1230 the structural similarity of 2-deoxy-D-glucose with mannose 1206:1264 Additionally, due to the structural similarity of 2-deoxy-D-glucose with mannose, we could confirm that the mechanism by which 2-deoxy-D-glucose predominantly acts in leukemia is via modification in N-linked glycosylation, leading to endoplasmic reticulum stress and consequently induction of the unfolded protein response. 28814986 2 50 theme poor 366:369 arg1 outcome 380:386 poor clinical outcome 366:386 poor clinical outcome 366:386 Resistance to this class of drugs represents one of the strongest indicators of poor clinical outcome. 28814986 3 51 theme glucose 512:518 arg1 demand 502:507 a higher demand 493:507 a higher demand of glucose associated with a deregulation of metabolic pathways 493:571 We show that leukemic cells, which are resistant to the glucocorticoid drug methylprednisolone, display a higher demand of glucose associated with a deregulation of metabolic pathways, in comparison to sensitive cells. 28814986 5 52 theme solid 826:830 arg1 tumors 832:837 solid tumors 826:837 solid tumors 826:837 Unlike solid tumors, where 2-deoxy-D-glucose promotes inhibition of glycolysis by hexokinase II exclusively under hypoxic conditions, we were able to show that the antileukemic effects of 2-deoxy-D-glucose are far more complex in leukemia. 28814986 5 53 theme hypoxic 933:939 arg1 conditions 941:950 hypoxic conditions 933:950 hypoxic conditions 933:950 Unlike solid tumors, where 2-deoxy-D-glucose promotes inhibition of glycolysis by hexokinase II exclusively under hypoxic conditions, we were able to show that the antileukemic effects of 2-deoxy-D-glucose are far more complex in leukemia. 28814986 1 54 theme childhood 172:180 arg1 leukemia 202:209 childhood acute lymphoblastic leukemia 172:209 childhood acute lymphoblastic leukemia 172:209 In childhood acute lymphoblastic leukemia, treatment failure is associated with resistance to glucocorticoid agents. 28814986 5 55 from leukemia 1049:1056 arg1 effects 996:1002 the antileukemic effects 979:1002 the antileukemic effects of 2-deoxy-D-glucose 979:1023 Unlike solid tumors, where 2-deoxy-D-glucose promotes inhibition of glycolysis by hexokinase II exclusively under hypoxic conditions, we were able to show that the antileukemic effects of 2-deoxy-D-glucose are far more complex in leukemia. 28814986 5 55 from leukemia 1049:1056 arg1 complex 1038:1044 complex 1038:1044 complex 1038:1044 Unlike solid tumors, where 2-deoxy-D-glucose promotes inhibition of glycolysis by hexokinase II exclusively under hypoxic conditions, we were able to show that the antileukemic effects of 2-deoxy-D-glucose are far more complex in leukemia. 28814986 0 56 from Sensitivity 41:51 arg1 Leukemia 76:83 Acute Lymphoblastic Leukemia 56:83 Acute Lymphoblastic Leukemia 56:83 2-Deoxy-D-glucose Restore Glucocorticoid Sensitivity in Acute Lymphoblastic Leukemia via Modification of N-Linked Glycosylation in an Oxygen Tension-Independent Manner. 28814986 7 57 theme unfolded 1482:1489 arg1 response 1499:1506 the unfolded protein response 1478:1506 the unfolded protein response 1478:1506 Additionally, due to the structural similarity of 2-deoxy-D-glucose with mannose, we could confirm that the mechanism by which 2-deoxy-D-glucose predominantly acts in leukemia is via modification in N-linked glycosylation, leading to endoplasmic reticulum stress and consequently induction of the unfolded protein response. 28814986 7 58 theme N-linked 1384:1391 arg1 glycosylation 1393:1405 N-linked glycosylation 1384:1405 N-linked glycosylation 1384:1405 Additionally, due to the structural similarity of 2-deoxy-D-glucose with mannose, we could confirm that the mechanism by which 2-deoxy-D-glucose predominantly acts in leukemia is via modification in N-linked glycosylation, leading to endoplasmic reticulum stress and consequently induction of the unfolded protein response. 28814986 1 59 theme acute 182:186 arg1 leukemia 202:209 childhood acute lymphoblastic leukemia 172:209 childhood acute lymphoblastic leukemia 172:209 In childhood acute lymphoblastic leukemia, treatment failure is associated with resistance to glucocorticoid agents. 28814986 7 60 with similarity 1221:1230 arg1 mannose 1258:1264 mannose 1258:1264 mannose 1258:1264 Additionally, due to the structural similarity of 2-deoxy-D-glucose with mannose, we could confirm that the mechanism by which 2-deoxy-D-glucose predominantly acts in leukemia is via modification in N-linked glycosylation, leading to endoplasmic reticulum stress and consequently induction of the unfolded protein response. 28814986 3 61 theme leukemic 402:409 arg1 cells 411:415 leukemic cells 402:415 leukemic cells 402:415 We show that leukemic cells, which are resistant to the glucocorticoid drug methylprednisolone, display a higher demand of glucose associated with a deregulation of metabolic pathways, in comparison to sensitive cells. 28491011 6 0 theme benign 959:964 arg1 cystadenoma 944:954 serous cystadenoma 937:954 serous cystadenoma 937:954 In this study, we used an integrated proteomics and glycoproteomics approach to analyze global glycoprotein abundance and glycosylation occupancy for proteins from high-grade ovarian serous carcinoma (HGSC) and serous cystadenoma, a benign epithelial ovarian tumor, by using LC-MS/MS-based technique. 28491011 6 0 theme benign 959:964 arg1 tumor 985:989 a benign epithelial ovarian tumor 957:989 a benign epithelial ovarian tumor 957:989 In this study, we used an integrated proteomics and glycoproteomics approach to analyze global glycoprotein abundance and glycosylation occupancy for proteins from high-grade ovarian serous carcinoma (HGSC) and serous cystadenoma, a benign epithelial ovarian tumor, by using LC-MS/MS-based technique. 28491011 9 1 theme glycosite-containing 1530:1549 arg1 peptides 1551:1558 the identified N-linked glycosite-containing peptides 1506:1558 the identified N-linked glycosite-containing peptides 1506:1558 Among the identified N-linked glycosite-containing peptides, the relative abundances of glycosite-containing peptide and the glycoprotein levels were compared using glycoproteomic and proteomic data. 28491011 5 2 theme potential 684:692 arg1 changes 707:713 potential glycoprotein changes 684:713 potential glycoprotein changes in cancer 684:723 In addition to glycoprotein expressions, the analysis of protein glycosylation occupancy could be important for the understanding of cancer biology as well as the identification of potential glycoprotein changes in cancer. 28491011 9 3 theme relative 1565:1572 arg1 abundances 1574:1583 the relative abundances 1561:1583 the relative abundances of glycosite-containing peptide 1561:1615 Among the identified N-linked glycosite-containing peptides, the relative abundances of glycosite-containing peptide and the glycoprotein levels were compared using glycoproteomic and proteomic data. 28491011 10 4 with peptides 1725:1732 arg1 changes 1746:1752 unique changes 1739:1752 unique changes in glycosylation occupancies rather than the protein expression levels 1739:1823 The glycosite-containing peptides with unique changes in glycosylation occupancies rather than the protein expression levels were identified. 28491011 5 5 theme changes 707:713 arg1 identification 666:679 the identification 662:679 cancer biology as well as the identification of potential glycoprotein changes in cancer 636:723 In addition to glycoprotein expressions, the analysis of protein glycosylation occupancy could be important for the understanding of cancer biology as well as the identification of potential glycoprotein changes in cancer. 28491011 5 5 theme changes 707:713 arg1 biology 643:649 cancer biology 636:649 cancer biology as well as the identification of potential glycoprotein changes in cancer 636:723 In addition to glycoprotein expressions, the analysis of protein glycosylation occupancy could be important for the understanding of cancer biology as well as the identification of potential glycoprotein changes in cancer. 28491011 6 6 theme glycosylation 848:860 arg1 occupancy 862:870 glycosylation occupancy 848:870 glycosylation occupancy 848:870 In this study, we used an integrated proteomics and glycoproteomics approach to analyze global glycoprotein abundance and glycosylation occupancy for proteins from high-grade ovarian serous carcinoma (HGSC) and serous cystadenoma, a benign epithelial ovarian tumor, by using LC-MS/MS-based technique. 28491011 6 7 theme serous 937:942 arg1 cystadenoma 944:954 serous cystadenoma 937:954 serous cystadenoma 937:954 In this study, we used an integrated proteomics and glycoproteomics approach to analyze global glycoprotein abundance and glycosylation occupancy for proteins from high-grade ovarian serous carcinoma (HGSC) and serous cystadenoma, a benign epithelial ovarian tumor, by using LC-MS/MS-based technique. 28491011 6 7 theme serous 937:942 arg1 tumor 985:989 a benign epithelial ovarian tumor 957:989 a benign epithelial ovarian tumor 957:989 In this study, we used an integrated proteomics and glycoproteomics approach to analyze global glycoprotein abundance and glycosylation occupancy for proteins from high-grade ovarian serous carcinoma (HGSC) and serous cystadenoma, a benign epithelial ovarian tumor, by using LC-MS/MS-based technique. 28491011 12 8 theme cancer 2390:2395 arg1 biology 2397:2403 ovarian cancer biology 2382:2403 ovarian cancer biology 2382:2403 Specific changes in glycoprotein expression or glycosylation occupancy have the potential to be used in the discrimination between benign and malignant epithelial ovarian tumors and to improve our understanding of ovarian cancer biology. 28491011 7 9 theme absolute 1171:1178 arg1 quantitation 1180:1191 relative and absolute quantitation 1158:1191 relative and absolute quantitation 1158:1191 METHODS Fresh-frozen ovarian HGSC tissues and benign serous cystadenoma cases were quantitatively analyzed using isobaric tags for relative and absolute quantitation for both global and glycoproteomic analyses by two dimensional fractionation followed by LC-MS/MS analysis using a Orbitrap Velos mass spectrometer. 28491011 1 10 theme heterogeneous 206:218 arg1 group 220:224 a heterogeneous group 204:224 a heterogeneous group of diseases with a poor 5-year survival rate 204:269 BACKGROUND Epithelial ovarian carcinomas encompass a heterogeneous group of diseases with a poor 5-year survival rate. 28491011 1 10 theme heterogeneous 206:218 arg1 diseases 229:236 diseases 229:236 diseases 229:236 BACKGROUND Epithelial ovarian carcinomas encompass a heterogeneous group of diseases with a poor 5-year survival rate. 28491011 10 11 theme protein 1799:1805 arg1 levels 1818:1823 the protein expression levels 1795:1823 glycosylation occupancies rather than the protein expression levels 1757:1823 The glycosite-containing peptides with unique changes in glycosylation occupancies rather than the protein expression levels were identified. 28491011 7 12 theme relative 1158:1165 arg1 quantitation 1180:1191 relative and absolute quantitation 1158:1191 relative and absolute quantitation 1158:1191 METHODS Fresh-frozen ovarian HGSC tissues and benign serous cystadenoma cases were quantitatively analyzed using isobaric tags for relative and absolute quantitation for both global and glycoproteomic analyses by two dimensional fractionation followed by LC-MS/MS analysis using a Orbitrap Velos mass spectrometer. 28491011 6 13 theme global 814:819 arg1 abundance 834:842 global glycoprotein abundance 814:842 global glycoprotein abundance 814:842 In this study, we used an integrated proteomics and glycoproteomics approach to analyze global glycoprotein abundance and glycosylation occupancy for proteins from high-grade ovarian serous carcinoma (HGSC) and serous cystadenoma, a benign epithelial ovarian tumor, by using LC-MS/MS-based technique. 28491011 7 14 theme global 1202:1207 arg1 analyses 1228:1235 both global and glycoproteomic analyses 1197:1235 both global and glycoproteomic analyses by two dimensional fractionation followed by LC-MS/MS analysis using a Orbitrap Velos mass spectrometer 1197:1339 METHODS Fresh-frozen ovarian HGSC tissues and benign serous cystadenoma cases were quantitatively analyzed using isobaric tags for relative and absolute quantitation for both global and glycoproteomic analyses by two dimensional fractionation followed by LC-MS/MS analysis using a Orbitrap Velos mass spectrometer. 28491011 4 15 gly glycoproteins 377:389 arg1 targets 463:469 therapeutic targets 451:469 therapeutic targets as well as surrogates of tumor 451:500 These glycoproteins on cell surface or shed into the bloodstream could serve as therapeutic targets as well as surrogates of tumor. 28491011 4 15 gly glycoproteins 377:389 arg1 glycoproteins 377:389 These glycoproteins 371:389 These glycoproteins on cell surface or shed into the bloodstream 371:434 These glycoproteins on cell surface or shed into the bloodstream could serve as therapeutic targets as well as surrogates of tumor. 28491011 4 15 gly glycoproteins 377:389 arg1 surrogates 482:491 surrogates 482:491 therapeutic targets as well as surrogates of tumor 451:500 These glycoproteins on cell surface or shed into the bloodstream could serve as therapeutic targets as well as surrogates of tumor. 28491011 11 16 from expression 1983:1992 arg1 HGSC 2025:2028 HGSC 2025:2028 HGSC 2025:2028 CONCLUSION In this study, we presented an integrated proteomics and glycoproteomics approach to identify changes of glycoproteins in protein expression and glycosylation occupancy in HGSC and serous cystadenoma and determined the changes of glycosylation occupancy that are associated with malignant and benign tumor tissues. 28491011 11 16 from expression 1983:1992 arg1 cystadenoma 2041:2051 serous cystadenoma 2034:2051 serous cystadenoma 2034:2051 CONCLUSION In this study, we presented an integrated proteomics and glycoproteomics approach to identify changes of glycoproteins in protein expression and glycosylation occupancy in HGSC and serous cystadenoma and determined the changes of glycosylation occupancy that are associated with malignant and benign tumor tissues. 28491011 8 17 theme N-linked 1363:1370 arg1 peptides 1393:1400 N-linked glycosite-containing peptides 1363:1400 N-linked glycosite-containing peptides 1363:1400 RESULTS Proteins and N-linked glycosite-containing peptides were identified and quantified using the integrated global proteomic and glycoproteomic approach. 28491011 0 18 theme ovarian 137:143 arg1 tumors 145:150 benign and malignant epithelial ovarian tumors 105:150 benign and malignant epithelial ovarian tumors 105:150 An integrated proteomic and glycoproteomic approach uncovers differences in glycosylation occupancy from benign and malignant epithelial ovarian tumors. 28491011 12 19 theme glycoprotein 2188:2199 arg1 expression 2201:2210 glycoprotein expression 2188:2210 glycoprotein expression 2188:2210 Specific changes in glycoprotein expression or glycosylation occupancy have the potential to be used in the discrimination between benign and malignant epithelial ovarian tumors and to improve our understanding of ovarian cancer biology. 28491011 7 20 theme benign 1073:1078 arg1 cystadenoma 1087:1097 benign serous cystadenoma 1073:1097 benign serous cystadenoma cases 1073:1103 METHODS Fresh-frozen ovarian HGSC tissues and benign serous cystadenoma cases were quantitatively analyzed using isobaric tags for relative and absolute quantitation for both global and glycoproteomic analyses by two dimensional fractionation followed by LC-MS/MS analysis using a Orbitrap Velos mass spectrometer. 28491011 1 21 theme poor 245:248 arg1 rate 266:269 a poor 5-year survival rate 243:269 a poor 5-year survival rate 243:269 BACKGROUND Epithelial ovarian carcinomas encompass a heterogeneous group of diseases with a poor 5-year survival rate. 28491011 3 22 theme serum 332:336 arg1 glycoproteins 356:368 glycoproteins 356:368 glycoproteins 356:368 Most FDA-approved serum tumor markers are glycoproteins. 28491011 3 22 theme serum 332:336 arg1 markers 344:350 Most FDA-approved serum tumor markers 314:350 Most FDA-approved serum tumor markers 314:350 Most FDA-approved serum tumor markers are glycoproteins. 28491011 4 23 from glycoproteins 377:389 arg1 shed 410:413 shed 410:413 shed 410:413 These glycoproteins on cell surface or shed into the bloodstream could serve as therapeutic targets as well as surrogates of tumor. 28491011 4 23 from glycoproteins 377:389 arg1 surface 399:405 cell surface 394:405 cell surface 394:405 These glycoproteins on cell surface or shed into the bloodstream could serve as therapeutic targets as well as surrogates of tumor. 28491011 9 24 theme glycoproteomic 1665:1678 arg1 data 1694:1697 glycoproteomic and proteomic data 1665:1697 glycoproteomic and proteomic data 1665:1697 Among the identified N-linked glycosite-containing peptides, the relative abundances of glycosite-containing peptide and the glycoprotein levels were compared using glycoproteomic and proteomic data. 28491011 6 25 theme ovarian 977:983 arg1 cystadenoma 944:954 serous cystadenoma 937:954 serous cystadenoma 937:954 In this study, we used an integrated proteomics and glycoproteomics approach to analyze global glycoprotein abundance and glycosylation occupancy for proteins from high-grade ovarian serous carcinoma (HGSC) and serous cystadenoma, a benign epithelial ovarian tumor, by using LC-MS/MS-based technique. 28491011 6 25 theme ovarian 977:983 arg1 tumor 985:989 a benign epithelial ovarian tumor 957:989 a benign epithelial ovarian tumor 957:989 In this study, we used an integrated proteomics and glycoproteomics approach to analyze global glycoprotein abundance and glycosylation occupancy for proteins from high-grade ovarian serous carcinoma (HGSC) and serous cystadenoma, a benign epithelial ovarian tumor, by using LC-MS/MS-based technique. 28491011 3 26 theme Most 314:317 arg1 glycoproteins 356:368 glycoproteins 356:368 glycoproteins 356:368 Most FDA-approved serum tumor markers are glycoproteins. 28491011 3 26 theme Most 314:317 arg1 markers 344:350 Most FDA-approved serum tumor markers 314:350 Most FDA-approved serum tumor markers 314:350 Most FDA-approved serum tumor markers are glycoproteins. 28491011 9 27 gly glycoprotein 1625:1636 arg1 glycoprotein 1625:1636 the glycoprotein levels 1621:1643 the glycoprotein levels 1621:1643 Among the identified N-linked glycosite-containing peptides, the relative abundances of glycosite-containing peptide and the glycoprotein levels were compared using glycoproteomic and proteomic data. 28491011 7 28 theme ovarian 1048:1054 arg1 tissues 1061:1067 ovarian HGSC tissues 1048:1067 ovarian HGSC tissues 1048:1067 METHODS Fresh-frozen ovarian HGSC tissues and benign serous cystadenoma cases were quantitatively analyzed using isobaric tags for relative and absolute quantitation for both global and glycoproteomic analyses by two dimensional fractionation followed by LC-MS/MS analysis using a Orbitrap Velos mass spectrometer. 28491011 1 29 theme BACKGROUND 153:162 arg1 carcinomas 183:192 BACKGROUND Epithelial ovarian carcinomas 153:192 BACKGROUND Epithelial ovarian carcinomas 153:192 BACKGROUND Epithelial ovarian carcinomas encompass a heterogeneous group of diseases with a poor 5-year survival rate. 28491011 7 30 theme mass 1323:1326 arg1 spectrometer 1328:1339 a Orbitrap Velos mass spectrometer 1306:1339 a Orbitrap Velos mass spectrometer 1306:1339 METHODS Fresh-frozen ovarian HGSC tissues and benign serous cystadenoma cases were quantitatively analyzed using isobaric tags for relative and absolute quantitation for both global and glycoproteomic analyses by two dimensional fractionation followed by LC-MS/MS analysis using a Orbitrap Velos mass spectrometer. 28491011 2 31 theme Serous 272:277 arg1 type 308:311 the most common type 292:311 the most common type 292:311 Serous carcinoma is the most common type. 28491011 2 31 theme Serous 272:277 arg1 carcinoma 279:287 Serous carcinoma 272:287 Serous carcinoma 272:287 Serous carcinoma is the most common type. 28491011 1 32 theme ovarian 175:181 arg1 carcinomas 183:192 BACKGROUND Epithelial ovarian carcinomas 153:192 BACKGROUND Epithelial ovarian carcinomas 153:192 BACKGROUND Epithelial ovarian carcinomas encompass a heterogeneous group of diseases with a poor 5-year survival rate. 28491011 8 33 theme global 1454:1459 arg1 approach 1490:1497 the integrated global proteomic and glycoproteomic approach 1439:1497 the integrated global proteomic and glycoproteomic approach 1439:1497 RESULTS Proteins and N-linked glycosite-containing peptides were identified and quantified using the integrated global proteomic and glycoproteomic approach. 28491011 11 34 theme glycosylation 1998:2010 arg1 occupancy 2012:2020 glycosylation occupancy 1998:2020 glycosylation occupancy 1998:2020 CONCLUSION In this study, we presented an integrated proteomics and glycoproteomics approach to identify changes of glycoproteins in protein expression and glycosylation occupancy in HGSC and serous cystadenoma and determined the changes of glycosylation occupancy that are associated with malignant and benign tumor tissues. 28491011 7 35 theme Orbitrap 1308:1315 arg1 spectrometer 1328:1339 a Orbitrap Velos mass spectrometer 1306:1339 a Orbitrap Velos mass spectrometer 1306:1339 METHODS Fresh-frozen ovarian HGSC tissues and benign serous cystadenoma cases were quantitatively analyzed using isobaric tags for relative and absolute quantitation for both global and glycoproteomic analyses by two dimensional fractionation followed by LC-MS/MS analysis using a Orbitrap Velos mass spectrometer. 28491011 0 36 theme benign 105:110 arg1 tumors 145:150 benign and malignant epithelial ovarian tumors 105:150 benign and malignant epithelial ovarian tumors 105:150 An integrated proteomic and glycoproteomic approach uncovers differences in glycosylation occupancy from benign and malignant epithelial ovarian tumors. 28491011 12 37 theme Specific 2168:2175 arg1 changes 2177:2183 Specific changes 2168:2183 Specific changes in glycoprotein expression or glycosylation occupancy 2168:2237 Specific changes in glycoprotein expression or glycosylation occupancy have the potential to be used in the discrimination between benign and malignant epithelial ovarian tumors and to improve our understanding of ovarian cancer biology. 28491011 5 38 theme biology 643:649 arg1 understanding 619:631 the understanding 615:631 the understanding of cancer biology as well as the identification of potential glycoprotein changes in cancer 615:723 In addition to glycoprotein expressions, the analysis of protein glycosylation occupancy could be important for the understanding of cancer biology as well as the identification of potential glycoprotein changes in cancer. 28491011 9 39 theme proteomic 1684:1692 arg1 data 1694:1697 glycoproteomic and proteomic data 1665:1697 glycoproteomic and proteomic data 1665:1697 Among the identified N-linked glycosite-containing peptides, the relative abundances of glycosite-containing peptide and the glycoprotein levels were compared using glycoproteomic and proteomic data. 28491011 4 40 theme tumor 496:500 arg1 targets 463:469 therapeutic targets 451:469 therapeutic targets as well as surrogates of tumor 451:500 These glycoproteins on cell surface or shed into the bloodstream could serve as therapeutic targets as well as surrogates of tumor. 28491011 4 40 theme tumor 496:500 arg1 glycoproteins 377:389 These glycoproteins 371:389 These glycoproteins on cell surface or shed into the bloodstream 371:434 These glycoproteins on cell surface or shed into the bloodstream could serve as therapeutic targets as well as surrogates of tumor. 28491011 4 40 theme tumor 496:500 arg1 surrogates 482:491 surrogates 482:491 therapeutic targets as well as surrogates of tumor 451:500 These glycoproteins on cell surface or shed into the bloodstream could serve as therapeutic targets as well as surrogates of tumor. 28491011 11 41 theme benign 2146:2151 arg1 tissues 2159:2165 malignant and benign tumor tissues 2132:2165 malignant and benign tumor tissues 2132:2165 CONCLUSION In this study, we presented an integrated proteomics and glycoproteomics approach to identify changes of glycoproteins in protein expression and glycosylation occupancy in HGSC and serous cystadenoma and determined the changes of glycosylation occupancy that are associated with malignant and benign tumor tissues. 28491011 0 42 theme malignant 116:124 arg1 tumors 145:150 benign and malignant epithelial ovarian tumors 105:150 benign and malignant epithelial ovarian tumors 105:150 An integrated proteomic and glycoproteomic approach uncovers differences in glycosylation occupancy from benign and malignant epithelial ovarian tumors. 28491011 10 43 theme glycosylation 1757:1769 arg1 occupancies 1771:1781 glycosylation occupancies 1757:1781 glycosylation occupancies rather than the protein expression levels 1757:1823 The glycosite-containing peptides with unique changes in glycosylation occupancies rather than the protein expression levels were identified. 28491011 0 44 theme glycosylation 76:88 arg1 occupancy 90:98 glycosylation occupancy 76:98 glycosylation occupancy from benign and malignant epithelial ovarian tumors 76:150 An integrated proteomic and glycoproteomic approach uncovers differences in glycosylation occupancy from benign and malignant epithelial ovarian tumors. 28491011 11 45 theme malignant 2132:2140 arg1 tissues 2159:2165 malignant and benign tumor tissues 2132:2165 malignant and benign tumor tissues 2132:2165 CONCLUSION In this study, we presented an integrated proteomics and glycoproteomics approach to identify changes of glycoproteins in protein expression and glycosylation occupancy in HGSC and serous cystadenoma and determined the changes of glycosylation occupancy that are associated with malignant and benign tumor tissues. 28491011 11 46 dep CONCLUSION 1842:1851 arg1 study 1861:1865 this study 1856:1865 this study 1856:1865 CONCLUSION In this study, we presented an integrated proteomics and glycoproteomics approach to identify changes of glycoproteins in protein expression and glycosylation occupancy in HGSC and serous cystadenoma and determined the changes of glycosylation occupancy that are associated with malignant and benign tumor tissues. 28491011 8 47 dep RESULTS 1342:1348 arg1 Proteins 1350:1357 Proteins 1350:1357 Proteins 1350:1357 RESULTS Proteins and N-linked glycosite-containing peptides were identified and quantified using the integrated global proteomic and glycoproteomic approach. 28491011 8 47 dep RESULTS 1342:1348 arg1 peptides 1393:1400 N-linked glycosite-containing peptides 1363:1400 N-linked glycosite-containing peptides 1363:1400 RESULTS Proteins and N-linked glycosite-containing peptides were identified and quantified using the integrated global proteomic and glycoproteomic approach. 28491011 11 48 gly glycoproteins 1958:1970 arg1 glycoproteins 1958:1970 glycoproteins 1958:1970 glycoproteins 1958:1970 CONCLUSION In this study, we presented an integrated proteomics and glycoproteomics approach to identify changes of glycoproteins in protein expression and glycosylation occupancy in HGSC and serous cystadenoma and determined the changes of glycosylation occupancy that are associated with malignant and benign tumor tissues. 28491011 7 49 dep Fresh-frozen 1035:1046 arg1 cases 1099:1103 benign serous cystadenoma cases 1073:1103 benign serous cystadenoma cases 1073:1103 METHODS Fresh-frozen ovarian HGSC tissues and benign serous cystadenoma cases were quantitatively analyzed using isobaric tags for relative and absolute quantitation for both global and glycoproteomic analyses by two dimensional fractionation followed by LC-MS/MS analysis using a Orbitrap Velos mass spectrometer. 28491011 7 49 dep Fresh-frozen 1035:1046 arg1 tissues 1061:1067 ovarian HGSC tissues 1048:1067 ovarian HGSC tissues 1048:1067 METHODS Fresh-frozen ovarian HGSC tissues and benign serous cystadenoma cases were quantitatively analyzed using isobaric tags for relative and absolute quantitation for both global and glycoproteomic analyses by two dimensional fractionation followed by LC-MS/MS analysis using a Orbitrap Velos mass spectrometer. 28491011 7 50 theme dimensional 1244:1254 arg1 fractionation 1256:1268 two dimensional fractionation 1240:1268 two dimensional fractionation followed by LC-MS/MS analysis using a Orbitrap Velos mass spectrometer 1240:1339 METHODS Fresh-frozen ovarian HGSC tissues and benign serous cystadenoma cases were quantitatively analyzed using isobaric tags for relative and absolute quantitation for both global and glycoproteomic analyses by two dimensional fractionation followed by LC-MS/MS analysis using a Orbitrap Velos mass spectrometer. 28491011 1 51 theme Epithelial 164:173 arg1 carcinomas 183:192 BACKGROUND Epithelial ovarian carcinomas 153:192 BACKGROUND Epithelial ovarian carcinomas 153:192 BACKGROUND Epithelial ovarian carcinomas encompass a heterogeneous group of diseases with a poor 5-year survival rate. 28491011 11 52 theme glycoproteomics 1910:1924 arg1 approach 1926:1933 an integrated proteomics and glycoproteomics approach 1881:1933 an integrated proteomics and glycoproteomics approach to identify changes of glycoproteins in protein expression and glycosylation occupancy in HGSC and serous cystadenoma 1881:2051 CONCLUSION In this study, we presented an integrated proteomics and glycoproteomics approach to identify changes of glycoproteins in protein expression and glycosylation occupancy in HGSC and serous cystadenoma and determined the changes of glycosylation occupancy that are associated with malignant and benign tumor tissues. 28491011 0 53 theme glycoproteomic 28:41 arg1 approach 43:50 An integrated proteomic and glycoproteomic approach 0:50 approach 43:50 An integrated proteomic and glycoproteomic approach uncovers differences in glycosylation occupancy from benign and malignant epithelial ovarian tumors. 28491011 10 54 from changes 1746:1752 arg1 occupancies 1771:1781 glycosylation occupancies 1757:1781 glycosylation occupancies rather than the protein expression levels 1757:1823 The glycosite-containing peptides with unique changes in glycosylation occupancies rather than the protein expression levels were identified. 28491011 10 54 from changes 1746:1752 arg1 levels 1818:1823 the protein expression levels 1795:1823 glycosylation occupancies rather than the protein expression levels 1757:1823 The glycosite-containing peptides with unique changes in glycosylation occupancies rather than the protein expression levels were identified. 28491011 10 55 theme glycosite-containing 1704:1723 arg1 peptides 1725:1732 The glycosite-containing peptides 1700:1732 The glycosite-containing peptides with unique changes in glycosylation occupancies rather than the protein expression levels 1700:1823 The glycosite-containing peptides with unique changes in glycosylation occupancies rather than the protein expression levels were identified. 28491011 11 56 theme proteomics 1895:1904 arg1 approach 1926:1933 an integrated proteomics and glycoproteomics approach 1881:1933 an integrated proteomics and glycoproteomics approach to identify changes of glycoproteins in protein expression and glycosylation occupancy in HGSC and serous cystadenoma 1881:2051 CONCLUSION In this study, we presented an integrated proteomics and glycoproteomics approach to identify changes of glycoproteins in protein expression and glycosylation occupancy in HGSC and serous cystadenoma and determined the changes of glycosylation occupancy that are associated with malignant and benign tumor tissues. 28491011 11 57 theme glycosylation 2083:2095 arg1 occupancy 2097:2105 glycosylation occupancy 2083:2105 glycosylation occupancy 2083:2105 CONCLUSION In this study, we presented an integrated proteomics and glycoproteomics approach to identify changes of glycoproteins in protein expression and glycosylation occupancy in HGSC and serous cystadenoma and determined the changes of glycosylation occupancy that are associated with malignant and benign tumor tissues. 28491011 7 58 theme glycoproteomic 1213:1226 arg1 analyses 1228:1235 both global and glycoproteomic analyses 1197:1235 both global and glycoproteomic analyses by two dimensional fractionation followed by LC-MS/MS analysis using a Orbitrap Velos mass spectrometer 1197:1339 METHODS Fresh-frozen ovarian HGSC tissues and benign serous cystadenoma cases were quantitatively analyzed using isobaric tags for relative and absolute quantitation for both global and glycoproteomic analyses by two dimensional fractionation followed by LC-MS/MS analysis using a Orbitrap Velos mass spectrometer. 28491011 3 59 gly glycoproteins 356:368 arg1 glycoproteins 356:368 glycoproteins 356:368 glycoproteins 356:368 Most FDA-approved serum tumor markers are glycoproteins. 28491011 3 59 gly glycoproteins 356:368 arg1 markers 344:350 Most FDA-approved serum tumor markers 314:350 Most FDA-approved serum tumor markers 314:350 Most FDA-approved serum tumor markers are glycoproteins. 28491011 6 60 theme ovarian 901:907 arg1 carcinoma 916:924 high-grade ovarian serous carcinoma 890:924 high-grade ovarian serous carcinoma (HGSC) 890:931 In this study, we used an integrated proteomics and glycoproteomics approach to analyze global glycoprotein abundance and glycosylation occupancy for proteins from high-grade ovarian serous carcinoma (HGSC) and serous cystadenoma, a benign epithelial ovarian tumor, by using LC-MS/MS-based technique. 28491011 6 60 theme ovarian 901:907 arg1 HGSC 927:930 HGSC 927:930 HGSC 927:930 In this study, we used an integrated proteomics and glycoproteomics approach to analyze global glycoprotein abundance and glycosylation occupancy for proteins from high-grade ovarian serous carcinoma (HGSC) and serous cystadenoma, a benign epithelial ovarian tumor, by using LC-MS/MS-based technique. 28491011 4 61 theme cell 394:397 arg1 surface 399:405 cell surface 394:405 cell surface 394:405 These glycoproteins on cell surface or shed into the bloodstream could serve as therapeutic targets as well as surrogates of tumor. 28491011 11 62 attach presented 1871:1879 arg2 we 1868:1869 we 1868:1869 we 1868:1869 CONCLUSION In this study, we presented an integrated proteomics and glycoproteomics approach to identify changes of glycoproteins in protein expression and glycosylation occupancy in HGSC and serous cystadenoma and determined the changes of glycosylation occupancy that are associated with malignant and benign tumor tissues. 28491011 11 62 attach presented 1871:1879 arg1 CONCLUSION 1842:1851 CONCLUSION 1842:1851 CONCLUSION 1842:1851 CONCLUSION In this study, we presented an integrated proteomics and glycoproteomics approach to identify changes of glycoproteins in protein expression and glycosylation occupancy in HGSC and serous cystadenoma and determined the changes of glycosylation occupancy that are associated with malignant and benign tumor tissues. 28491011 1 63 theme 5-year 250:255 arg1 rate 266:269 a poor 5-year survival rate 243:269 a poor 5-year survival rate 243:269 BACKGROUND Epithelial ovarian carcinomas encompass a heterogeneous group of diseases with a poor 5-year survival rate. 28491011 8 64 link N-linked 1363:1370 arg1 peptides 1393:1400 N-linked glycosite-containing peptides 1363:1400 N-linked glycosite-containing peptides 1363:1400 RESULTS Proteins and N-linked glycosite-containing peptides were identified and quantified using the integrated global proteomic and glycoproteomic approach. 28491011 0 65 dep proteomic 14:22 arg1 integrated 3:12 integrated 3:12 integrated 3:12 An integrated proteomic and glycoproteomic approach uncovers differences in glycosylation occupancy from benign and malignant epithelial ovarian tumors. 28491011 12 66 theme benign 2299:2304 arg1 tumors 2339:2344 benign and malignant epithelial ovarian tumors 2299:2344 benign and malignant epithelial ovarian tumors 2299:2344 Specific changes in glycoprotein expression or glycosylation occupancy have the potential to be used in the discrimination between benign and malignant epithelial ovarian tumors and to improve our understanding of ovarian cancer biology. 28491011 6 67 theme integrated 752:761 arg1 proteomics 763:772 an integrated proteomics and glycoproteomics approach 749:801 proteomics 763:772 In this study, we used an integrated proteomics and glycoproteomics approach to analyze global glycoprotein abundance and glycosylation occupancy for proteins from high-grade ovarian serous carcinoma (HGSC) and serous cystadenoma, a benign epithelial ovarian tumor, by using LC-MS/MS-based technique. 28491011 9 68 theme peptide 1609:1615 arg1 levels 1638:1643 the glycoprotein levels 1621:1643 the glycoprotein levels 1621:1643 Among the identified N-linked glycosite-containing peptides, the relative abundances of glycosite-containing peptide and the glycoprotein levels were compared using glycoproteomic and proteomic data. 28491011 9 68 theme peptide 1609:1615 arg1 abundances 1574:1583 the relative abundances 1561:1583 the relative abundances of glycosite-containing peptide 1561:1615 Among the identified N-linked glycosite-containing peptides, the relative abundances of glycosite-containing peptide and the glycoprotein levels were compared using glycoproteomic and proteomic data. 28491011 6 69 theme epithelial 966:975 arg1 cystadenoma 944:954 serous cystadenoma 937:954 serous cystadenoma 937:954 In this study, we used an integrated proteomics and glycoproteomics approach to analyze global glycoprotein abundance and glycosylation occupancy for proteins from high-grade ovarian serous carcinoma (HGSC) and serous cystadenoma, a benign epithelial ovarian tumor, by using LC-MS/MS-based technique. 28491011 6 69 theme epithelial 966:975 arg1 tumor 985:989 a benign epithelial ovarian tumor 957:989 a benign epithelial ovarian tumor 957:989 In this study, we used an integrated proteomics and glycoproteomics approach to analyze global glycoprotein abundance and glycosylation occupancy for proteins from high-grade ovarian serous carcinoma (HGSC) and serous cystadenoma, a benign epithelial ovarian tumor, by using LC-MS/MS-based technique. 28491011 10 70 theme expression 1807:1816 arg1 levels 1818:1823 the protein expression levels 1795:1823 glycosylation occupancies rather than the protein expression levels 1757:1823 The glycosite-containing peptides with unique changes in glycosylation occupancies rather than the protein expression levels were identified. 28491011 12 71 gly glycoprotein 2188:2199 arg1 glycoprotein 2188:2199 glycoprotein expression 2188:2210 glycoprotein expression 2188:2210 Specific changes in glycoprotein expression or glycosylation occupancy have the potential to be used in the discrimination between benign and malignant epithelial ovarian tumors and to improve our understanding of ovarian cancer biology. 28491011 5 72 theme glycoprotein 694:705 arg1 changes 707:713 potential glycoprotein changes 684:713 potential glycoprotein changes in cancer 684:723 In addition to glycoprotein expressions, the analysis of protein glycosylation occupancy could be important for the understanding of cancer biology as well as the identification of potential glycoprotein changes in cancer. 28491011 7 73 theme Fresh-frozen 1035:1046 arg1 METHODS 1027:1033 METHODS 1027:1033 METHODS Fresh-frozen ovarian HGSC tissues and benign serous cystadenoma cases 1027:1103 METHODS Fresh-frozen ovarian HGSC tissues and benign serous cystadenoma cases were quantitatively analyzed using isobaric tags for relative and absolute quantitation for both global and glycoproteomic analyses by two dimensional fractionation followed by LC-MS/MS analysis using a Orbitrap Velos mass spectrometer. 28491011 12 74 theme epithelial 2320:2329 arg1 tumors 2339:2344 benign and malignant epithelial ovarian tumors 2299:2344 benign and malignant epithelial ovarian tumors 2299:2344 Specific changes in glycoprotein expression or glycosylation occupancy have the potential to be used in the discrimination between benign and malignant epithelial ovarian tumors and to improve our understanding of ovarian cancer biology. 28491011 6 75 from cystadenoma 944:954 arg1 proteins 876:883 proteins 876:883 proteins from high-grade ovarian serous carcinoma (HGSC) and serous cystadenoma, a benign epithelial ovarian tumor, 876:990 In this study, we used an integrated proteomics and glycoproteomics approach to analyze global glycoprotein abundance and glycosylation occupancy for proteins from high-grade ovarian serous carcinoma (HGSC) and serous cystadenoma, a benign epithelial ovarian tumor, by using LC-MS/MS-based technique. 28491011 2 76 theme common 301:306 arg1 type 308:311 the most common type 292:311 the most common type 292:311 Serous carcinoma is the most common type. 28491011 2 76 theme common 301:306 arg1 carcinoma 279:287 Serous carcinoma 272:287 Serous carcinoma 272:287 Serous carcinoma is the most common type. 28491011 5 77 theme glycoprotein 518:529 arg1 expressions 531:541 glycoprotein expressions 518:541 glycoprotein expressions 518:541 In addition to glycoprotein expressions, the analysis of protein glycosylation occupancy could be important for the understanding of cancer biology as well as the identification of potential glycoprotein changes in cancer. 28491011 9 78 theme glycosite-containing 1588:1607 arg1 peptide 1609:1615 glycosite-containing peptide 1588:1615 glycosite-containing peptide 1588:1615 Among the identified N-linked glycosite-containing peptides, the relative abundances of glycosite-containing peptide and the glycoprotein levels were compared using glycoproteomic and proteomic data. 28491011 12 79 theme ovarian 2382:2388 arg1 biology 2397:2403 ovarian cancer biology 2382:2403 ovarian cancer biology 2382:2403 Specific changes in glycoprotein expression or glycosylation occupancy have the potential to be used in the discrimination between benign and malignant epithelial ovarian tumors and to improve our understanding of ovarian cancer biology. 28491011 6 80 from carcinoma 916:924 arg1 proteins 876:883 proteins 876:883 proteins from high-grade ovarian serous carcinoma (HGSC) and serous cystadenoma, a benign epithelial ovarian tumor, 876:990 In this study, we used an integrated proteomics and glycoproteomics approach to analyze global glycoprotein abundance and glycosylation occupancy for proteins from high-grade ovarian serous carcinoma (HGSC) and serous cystadenoma, a benign epithelial ovarian tumor, by using LC-MS/MS-based technique. 28491011 6 81 theme glycoprotein 821:832 arg1 abundance 834:842 global glycoprotein abundance 814:842 global glycoprotein abundance 814:842 In this study, we used an integrated proteomics and glycoproteomics approach to analyze global glycoprotein abundance and glycosylation occupancy for proteins from high-grade ovarian serous carcinoma (HGSC) and serous cystadenoma, a benign epithelial ovarian tumor, by using LC-MS/MS-based technique. 28491011 12 82 theme glycosylation 2215:2227 arg1 occupancy 2229:2237 glycosylation occupancy 2215:2237 glycosylation occupancy 2215:2237 Specific changes in glycoprotein expression or glycosylation occupancy have the potential to be used in the discrimination between benign and malignant epithelial ovarian tumors and to improve our understanding of ovarian cancer biology. 28491011 6 83 gly glycoprotein 821:832 arg1 glycoprotein 821:832 global glycoprotein abundance 814:842 global glycoprotein abundance 814:842 In this study, we used an integrated proteomics and glycoproteomics approach to analyze global glycoprotein abundance and glycosylation occupancy for proteins from high-grade ovarian serous carcinoma (HGSC) and serous cystadenoma, a benign epithelial ovarian tumor, by using LC-MS/MS-based technique. 28491011 5 84 theme identification 666:679 arg1 understanding 619:631 the understanding 615:631 the understanding of cancer biology as well as the identification of potential glycoprotein changes in cancer 615:723 In addition to glycoprotein expressions, the analysis of protein glycosylation occupancy could be important for the understanding of cancer biology as well as the identification of potential glycoprotein changes in cancer. 28491011 9 85 link N-linked 1521:1528 arg1 peptides 1551:1558 the identified N-linked glycosite-containing peptides 1506:1558 the identified N-linked glycosite-containing peptides 1506:1558 Among the identified N-linked glycosite-containing peptides, the relative abundances of glycosite-containing peptide and the glycoprotein levels were compared using glycoproteomic and proteomic data. 28491011 5 86 gly glycoprotein 694:705 arg1 glycoprotein 694:705 potential glycoprotein changes 684:713 potential glycoprotein changes in cancer 684:723 In addition to glycoprotein expressions, the analysis of protein glycosylation occupancy could be important for the understanding of cancer biology as well as the identification of potential glycoprotein changes in cancer. 28491011 11 87 theme serous 2034:2039 arg1 cystadenoma 2041:2051 serous cystadenoma 2034:2051 serous cystadenoma 2034:2051 CONCLUSION In this study, we presented an integrated proteomics and glycoproteomics approach to identify changes of glycoproteins in protein expression and glycosylation occupancy in HGSC and serous cystadenoma and determined the changes of glycosylation occupancy that are associated with malignant and benign tumor tissues. 28491011 7 88 theme isobaric 1140:1147 arg1 tags 1149:1152 isobaric tags 1140:1152 isobaric tags for relative and absolute quantitation 1140:1191 METHODS Fresh-frozen ovarian HGSC tissues and benign serous cystadenoma cases were quantitatively analyzed using isobaric tags for relative and absolute quantitation for both global and glycoproteomic analyses by two dimensional fractionation followed by LC-MS/MS analysis using a Orbitrap Velos mass spectrometer. 28491011 1 89 theme diseases 229:236 arg1 group 220:224 a heterogeneous group 204:224 a heterogeneous group of diseases with a poor 5-year survival rate 204:269 BACKGROUND Epithelial ovarian carcinomas encompass a heterogeneous group of diseases with a poor 5-year survival rate. 28491011 1 89 theme diseases 229:236 arg1 diseases 229:236 diseases 229:236 diseases 229:236 BACKGROUND Epithelial ovarian carcinomas encompass a heterogeneous group of diseases with a poor 5-year survival rate. 28491011 6 90 theme LC-MS/MS-based 1001:1014 arg1 technique 1016:1024 LC-MS/MS-based technique 1001:1024 LC-MS/MS-based technique 1001:1024 In this study, we used an integrated proteomics and glycoproteomics approach to analyze global glycoprotein abundance and glycosylation occupancy for proteins from high-grade ovarian serous carcinoma (HGSC) and serous cystadenoma, a benign epithelial ovarian tumor, by using LC-MS/MS-based technique. 28491011 12 91 theme malignant 2310:2318 arg1 tumors 2339:2344 benign and malignant epithelial ovarian tumors 2299:2344 benign and malignant epithelial ovarian tumors 2299:2344 Specific changes in glycoprotein expression or glycosylation occupancy have the potential to be used in the discrimination between benign and malignant epithelial ovarian tumors and to improve our understanding of ovarian cancer biology. 28491011 12 92 theme biology 2397:2403 arg1 understanding 2365:2377 our understanding 2361:2377 our understanding of ovarian cancer biology 2361:2403 Specific changes in glycoprotein expression or glycosylation occupancy have the potential to be used in the discrimination between benign and malignant epithelial ovarian tumors and to improve our understanding of ovarian cancer biology. 28491011 11 93 from occupancy 2012:2020 arg1 HGSC 2025:2028 HGSC 2025:2028 HGSC 2025:2028 CONCLUSION In this study, we presented an integrated proteomics and glycoproteomics approach to identify changes of glycoproteins in protein expression and glycosylation occupancy in HGSC and serous cystadenoma and determined the changes of glycosylation occupancy that are associated with malignant and benign tumor tissues. 28491011 11 93 from occupancy 2012:2020 arg1 cystadenoma 2041:2051 serous cystadenoma 2034:2051 serous cystadenoma 2034:2051 CONCLUSION In this study, we presented an integrated proteomics and glycoproteomics approach to identify changes of glycoproteins in protein expression and glycosylation occupancy in HGSC and serous cystadenoma and determined the changes of glycosylation occupancy that are associated with malignant and benign tumor tissues. 28491011 5 94 dep expressions 531:541 arg1 addition 506:513 addition 506:513 addition 506:513 In addition to glycoprotein expressions, the analysis of protein glycosylation occupancy could be important for the understanding of cancer biology as well as the identification of potential glycoprotein changes in cancer. 28491011 8 95 theme glycosite-containing 1372:1391 arg1 peptides 1393:1400 N-linked glycosite-containing peptides 1363:1400 N-linked glycosite-containing peptides 1363:1400 RESULTS Proteins and N-linked glycosite-containing peptides were identified and quantified using the integrated global proteomic and glycoproteomic approach. 28491011 5 96 theme occupancy 582:590 arg1 important 601:609 important 601:609 important 601:609 In addition to glycoprotein expressions, the analysis of protein glycosylation occupancy could be important for the understanding of cancer biology as well as the identification of potential glycoprotein changes in cancer. 28491011 5 96 theme occupancy 582:590 arg1 analysis 548:555 the analysis 544:555 the analysis of protein glycosylation occupancy 544:590 In addition to glycoprotein expressions, the analysis of protein glycosylation occupancy could be important for the understanding of cancer biology as well as the identification of potential glycoprotein changes in cancer. 28491011 6 97 used used 744:747 arg2 we 741:742 we 741:742 we 741:742 In this study, we used an integrated proteomics and glycoproteomics approach to analyze global glycoprotein abundance and glycosylation occupancy for proteins from high-grade ovarian serous carcinoma (HGSC) and serous cystadenoma, a benign epithelial ovarian tumor, by using LC-MS/MS-based technique. 28491011 3 98 theme tumor 338:342 arg1 glycoproteins 356:368 glycoproteins 356:368 glycoproteins 356:368 Most FDA-approved serum tumor markers are glycoproteins. 28491011 3 98 theme tumor 338:342 arg1 markers 344:350 Most FDA-approved serum tumor markers 314:350 Most FDA-approved serum tumor markers 314:350 Most FDA-approved serum tumor markers are glycoproteins. 28491011 4 99 theme therapeutic 451:461 arg1 targets 463:469 therapeutic targets 451:469 therapeutic targets as well as surrogates of tumor 451:500 These glycoproteins on cell surface or shed into the bloodstream could serve as therapeutic targets as well as surrogates of tumor. 28491011 4 99 theme therapeutic 451:461 arg1 glycoproteins 377:389 These glycoproteins 371:389 These glycoproteins on cell surface or shed into the bloodstream 371:434 These glycoproteins on cell surface or shed into the bloodstream could serve as therapeutic targets as well as surrogates of tumor. 28491011 12 100 theme ovarian 2331:2337 arg1 tumors 2339:2344 benign and malignant epithelial ovarian tumors 2299:2344 benign and malignant epithelial ovarian tumors 2299:2344 Specific changes in glycoprotein expression or glycosylation occupancy have the potential to be used in the discrimination between benign and malignant epithelial ovarian tumors and to improve our understanding of ovarian cancer biology. 28491011 7 101 theme cystadenoma 1087:1097 arg1 cases 1099:1103 benign serous cystadenoma cases 1073:1103 benign serous cystadenoma cases 1073:1103 METHODS Fresh-frozen ovarian HGSC tissues and benign serous cystadenoma cases were quantitatively analyzed using isobaric tags for relative and absolute quantitation for both global and glycoproteomic analyses by two dimensional fractionation followed by LC-MS/MS analysis using a Orbitrap Velos mass spectrometer. 28491011 12 102 contain have 2239:2242 arg2 potential 2248:2256 the potential to be used in the discrimination between benign and malignant epithelial ovarian tumors and to improve our understanding of ovarian cancer biology 2244:2403 the potential to be used in the discrimination between benign and malignant epithelial ovarian tumors and to improve our understanding of ovarian cancer biology 2244:2403 Specific changes in glycoprotein expression or glycosylation occupancy have the potential to be used in the discrimination between benign and malignant epithelial ovarian tumors and to improve our understanding of ovarian cancer biology. 28491011 12 102 contain have 2239:2242 arg1 changes 2177:2183 Specific changes 2168:2183 Specific changes in glycoprotein expression or glycosylation occupancy 2168:2237 Specific changes in glycoprotein expression or glycosylation occupancy have the potential to be used in the discrimination between benign and malignant epithelial ovarian tumors and to improve our understanding of ovarian cancer biology. 28491011 12 103 from changes 2177:2183 arg1 expression 2201:2210 glycoprotein expression 2188:2210 glycoprotein expression 2188:2210 Specific changes in glycoprotein expression or glycosylation occupancy have the potential to be used in the discrimination between benign and malignant epithelial ovarian tumors and to improve our understanding of ovarian cancer biology. 28491011 12 103 from changes 2177:2183 arg1 occupancy 2229:2237 glycosylation occupancy 2215:2237 glycosylation occupancy 2215:2237 Specific changes in glycoprotein expression or glycosylation occupancy have the potential to be used in the discrimination between benign and malignant epithelial ovarian tumors and to improve our understanding of ovarian cancer biology. 28491011 3 104 theme FDA-approved 319:330 arg1 glycoproteins 356:368 glycoproteins 356:368 glycoproteins 356:368 Most FDA-approved serum tumor markers are glycoproteins. 28491011 3 104 theme FDA-approved 319:330 arg1 markers 344:350 Most FDA-approved serum tumor markers 314:350 Most FDA-approved serum tumor markers 314:350 Most FDA-approved serum tumor markers are glycoproteins. 28491011 11 105 theme protein 1975:1981 arg1 expression 1983:1992 protein expression 1975:1992 protein expression 1975:1992 CONCLUSION In this study, we presented an integrated proteomics and glycoproteomics approach to identify changes of glycoproteins in protein expression and glycosylation occupancy in HGSC and serous cystadenoma and determined the changes of glycosylation occupancy that are associated with malignant and benign tumor tissues. 28491011 7 106 theme Velos 1317:1321 arg1 spectrometer 1328:1339 a Orbitrap Velos mass spectrometer 1306:1339 a Orbitrap Velos mass spectrometer 1306:1339 METHODS Fresh-frozen ovarian HGSC tissues and benign serous cystadenoma cases were quantitatively analyzed using isobaric tags for relative and absolute quantitation for both global and glycoproteomic analyses by two dimensional fractionation followed by LC-MS/MS analysis using a Orbitrap Velos mass spectrometer. 28491011 7 107 theme HGSC 1056:1059 arg1 tissues 1061:1067 ovarian HGSC tissues 1048:1067 ovarian HGSC tissues 1048:1067 METHODS Fresh-frozen ovarian HGSC tissues and benign serous cystadenoma cases were quantitatively analyzed using isobaric tags for relative and absolute quantitation for both global and glycoproteomic analyses by two dimensional fractionation followed by LC-MS/MS analysis using a Orbitrap Velos mass spectrometer. 28491011 5 108 from biology 643:649 arg1 cancer 718:723 cancer 718:723 cancer 718:723 In addition to glycoprotein expressions, the analysis of protein glycosylation occupancy could be important for the understanding of cancer biology as well as the identification of potential glycoprotein changes in cancer. 28491011 5 109 gly glycoprotein 518:529 arg1 glycoprotein 518:529 glycoprotein expressions 518:541 glycoprotein expressions 518:541 In addition to glycoprotein expressions, the analysis of protein glycosylation occupancy could be important for the understanding of cancer biology as well as the identification of potential glycoprotein changes in cancer. 28491011 9 110 theme N-linked 1521:1528 arg1 peptides 1551:1558 the identified N-linked glycosite-containing peptides 1506:1558 the identified N-linked glycosite-containing peptides 1506:1558 Among the identified N-linked glycosite-containing peptides, the relative abundances of glycosite-containing peptide and the glycoprotein levels were compared using glycoproteomic and proteomic data. 28491011 11 111 theme glycoproteins 1958:1970 arg1 changes 1947:1953 changes 1947:1953 changes of glycoproteins in protein expression and glycosylation occupancy in HGSC and serous cystadenoma 1947:2051 CONCLUSION In this study, we presented an integrated proteomics and glycoproteomics approach to identify changes of glycoproteins in protein expression and glycosylation occupancy in HGSC and serous cystadenoma and determined the changes of glycosylation occupancy that are associated with malignant and benign tumor tissues. 28491011 5 112 theme protein 560:566 arg1 occupancy 582:590 protein glycosylation occupancy 560:590 protein glycosylation occupancy 560:590 In addition to glycoprotein expressions, the analysis of protein glycosylation occupancy could be important for the understanding of cancer biology as well as the identification of potential glycoprotein changes in cancer. 28491011 11 113 from changes 1947:1953 arg1 expression 1983:1992 protein expression 1975:1992 protein expression 1975:1992 CONCLUSION In this study, we presented an integrated proteomics and glycoproteomics approach to identify changes of glycoproteins in protein expression and glycosylation occupancy in HGSC and serous cystadenoma and determined the changes of glycosylation occupancy that are associated with malignant and benign tumor tissues. 28491011 11 113 from changes 1947:1953 arg1 occupancy 2012:2020 glycosylation occupancy 1998:2020 glycosylation occupancy 1998:2020 CONCLUSION In this study, we presented an integrated proteomics and glycoproteomics approach to identify changes of glycoproteins in protein expression and glycosylation occupancy in HGSC and serous cystadenoma and determined the changes of glycosylation occupancy that are associated with malignant and benign tumor tissues. 28491011 8 114 theme integrated 1443:1452 arg1 approach 1490:1497 the integrated global proteomic and glycoproteomic approach 1439:1497 the integrated global proteomic and glycoproteomic approach 1439:1497 RESULTS Proteins and N-linked glycosite-containing peptides were identified and quantified using the integrated global proteomic and glycoproteomic approach. 28491011 5 115 theme cancer 636:641 arg1 biology 643:649 cancer biology 636:649 cancer biology as well as the identification of potential glycoprotein changes in cancer 636:723 In addition to glycoprotein expressions, the analysis of protein glycosylation occupancy could be important for the understanding of cancer biology as well as the identification of potential glycoprotein changes in cancer. 28491011 0 116 from differences 61:71 arg1 occupancy 90:98 glycosylation occupancy 76:98 glycosylation occupancy from benign and malignant epithelial ovarian tumors 76:150 An integrated proteomic and glycoproteomic approach uncovers differences in glycosylation occupancy from benign and malignant epithelial ovarian tumors. 28491011 0 116 from differences 61:71 arg1 tumors 145:150 benign and malignant epithelial ovarian tumors 105:150 benign and malignant epithelial ovarian tumors 105:150 An integrated proteomic and glycoproteomic approach uncovers differences in glycosylation occupancy from benign and malignant epithelial ovarian tumors. 28491011 8 117 theme proteomic 1461:1469 arg1 approach 1490:1497 the integrated global proteomic and glycoproteomic approach 1439:1497 the integrated global proteomic and glycoproteomic approach 1439:1497 RESULTS Proteins and N-linked glycosite-containing peptides were identified and quantified using the integrated global proteomic and glycoproteomic approach. 28491011 9 118 theme glycoprotein 1625:1636 arg1 levels 1638:1643 the glycoprotein levels 1621:1643 the glycoprotein levels 1621:1643 Among the identified N-linked glycosite-containing peptides, the relative abundances of glycosite-containing peptide and the glycoprotein levels were compared using glycoproteomic and proteomic data. 28491011 0 119 theme epithelial 126:135 arg1 tumors 145:150 benign and malignant epithelial ovarian tumors 105:150 benign and malignant epithelial ovarian tumors 105:150 An integrated proteomic and glycoproteomic approach uncovers differences in glycosylation occupancy from benign and malignant epithelial ovarian tumors. 28491011 7 120 theme serous 1080:1085 arg1 cystadenoma 1087:1097 benign serous cystadenoma 1073:1097 benign serous cystadenoma cases 1073:1103 METHODS Fresh-frozen ovarian HGSC tissues and benign serous cystadenoma cases were quantitatively analyzed using isobaric tags for relative and absolute quantitation for both global and glycoproteomic analyses by two dimensional fractionation followed by LC-MS/MS analysis using a Orbitrap Velos mass spectrometer. 28491011 8 121 theme glycoproteomic 1475:1488 arg1 approach 1490:1497 the integrated global proteomic and glycoproteomic approach 1439:1497 the integrated global proteomic and glycoproteomic approach 1439:1497 RESULTS Proteins and N-linked glycosite-containing peptides were identified and quantified using the integrated global proteomic and glycoproteomic approach. 28491011 11 122 theme tumor 2153:2157 arg1 tissues 2159:2165 malignant and benign tumor tissues 2132:2165 malignant and benign tumor tissues 2132:2165 CONCLUSION In this study, we presented an integrated proteomics and glycoproteomics approach to identify changes of glycoproteins in protein expression and glycosylation occupancy in HGSC and serous cystadenoma and determined the changes of glycosylation occupancy that are associated with malignant and benign tumor tissues. 28491011 5 123 from identification 666:679 arg1 cancer 718:723 cancer 718:723 cancer 718:723 In addition to glycoprotein expressions, the analysis of protein glycosylation occupancy could be important for the understanding of cancer biology as well as the identification of potential glycoprotein changes in cancer. 28491011 12 124 dep potential 2248:2256 arg1 improve 2353:2359 improve 2353:2359 to improve our understanding of ovarian cancer biology 2350:2403 Specific changes in glycoprotein expression or glycosylation occupancy have the potential to be used in the discrimination between benign and malignant epithelial ovarian tumors and to improve our understanding of ovarian cancer biology. 28491011 12 124 dep potential 2248:2256 arg1 used 2264:2267 used 2264:2267 to be used in the discrimination between benign and malignant epithelial ovarian tumors 2258:2344 Specific changes in glycoprotein expression or glycosylation occupancy have the potential to be used in the discrimination between benign and malignant epithelial ovarian tumors and to improve our understanding of ovarian cancer biology. 28491011 11 125 theme integrated 1884:1893 arg1 approach 1926:1933 an integrated proteomics and glycoproteomics approach 1881:1933 an integrated proteomics and glycoproteomics approach to identify changes of glycoproteins in protein expression and glycosylation occupancy in HGSC and serous cystadenoma 1881:2051 CONCLUSION In this study, we presented an integrated proteomics and glycoproteomics approach to identify changes of glycoproteins in protein expression and glycosylation occupancy in HGSC and serous cystadenoma and determined the changes of glycosylation occupancy that are associated with malignant and benign tumor tissues. 28491011 7 126 theme LC-MS/MS 1282:1289 arg1 analysis 1291:1298 LC-MS/MS analysis 1282:1298 LC-MS/MS analysis using a Orbitrap Velos mass spectrometer 1282:1339 METHODS Fresh-frozen ovarian HGSC tissues and benign serous cystadenoma cases were quantitatively analyzed using isobaric tags for relative and absolute quantitation for both global and glycoproteomic analyses by two dimensional fractionation followed by LC-MS/MS analysis using a Orbitrap Velos mass spectrometer. 28491011 5 127 from changes 707:713 arg1 cancer 718:723 cancer 718:723 cancer 718:723 In addition to glycoprotein expressions, the analysis of protein glycosylation occupancy could be important for the understanding of cancer biology as well as the identification of potential glycoprotein changes in cancer. 28491011 1 128 with group 220:224 arg1 rate 266:269 a poor 5-year survival rate 243:269 a poor 5-year survival rate 243:269 BACKGROUND Epithelial ovarian carcinomas encompass a heterogeneous group of diseases with a poor 5-year survival rate. 28491011 6 129 theme serous 909:914 arg1 carcinoma 916:924 high-grade ovarian serous carcinoma 890:924 high-grade ovarian serous carcinoma (HGSC) 890:931 In this study, we used an integrated proteomics and glycoproteomics approach to analyze global glycoprotein abundance and glycosylation occupancy for proteins from high-grade ovarian serous carcinoma (HGSC) and serous cystadenoma, a benign epithelial ovarian tumor, by using LC-MS/MS-based technique. 28491011 6 129 theme serous 909:914 arg1 HGSC 927:930 HGSC 927:930 HGSC 927:930 In this study, we used an integrated proteomics and glycoproteomics approach to analyze global glycoprotein abundance and glycosylation occupancy for proteins from high-grade ovarian serous carcinoma (HGSC) and serous cystadenoma, a benign epithelial ovarian tumor, by using LC-MS/MS-based technique. 28491011 6 130 theme glycoproteomics 778:792 arg1 approach 794:801 an integrated proteomics and glycoproteomics approach 749:801 approach 794:801 In this study, we used an integrated proteomics and glycoproteomics approach to analyze global glycoprotein abundance and glycosylation occupancy for proteins from high-grade ovarian serous carcinoma (HGSC) and serous cystadenoma, a benign epithelial ovarian tumor, by using LC-MS/MS-based technique. 28491011 11 131 theme occupancy 2097:2105 arg1 changes 2072:2078 the changes 2068:2078 the changes of glycosylation occupancy that are associated with malignant and benign tumor tissues 2068:2165 CONCLUSION In this study, we presented an integrated proteomics and glycoproteomics approach to identify changes of glycoproteins in protein expression and glycosylation occupancy in HGSC and serous cystadenoma and determined the changes of glycosylation occupancy that are associated with malignant and benign tumor tissues. 28491011 9 132 theme identified 1510:1519 arg1 peptides 1551:1558 the identified N-linked glycosite-containing peptides 1506:1558 the identified N-linked glycosite-containing peptides 1506:1558 Among the identified N-linked glycosite-containing peptides, the relative abundances of glycosite-containing peptide and the glycoprotein levels were compared using glycoproteomic and proteomic data. 28491011 6 133 theme high-grade 890:899 arg1 carcinoma 916:924 high-grade ovarian serous carcinoma 890:924 high-grade ovarian serous carcinoma (HGSC) 890:931 In this study, we used an integrated proteomics and glycoproteomics approach to analyze global glycoprotein abundance and glycosylation occupancy for proteins from high-grade ovarian serous carcinoma (HGSC) and serous cystadenoma, a benign epithelial ovarian tumor, by using LC-MS/MS-based technique. 28491011 6 133 theme high-grade 890:899 arg1 HGSC 927:930 HGSC 927:930 HGSC 927:930 In this study, we used an integrated proteomics and glycoproteomics approach to analyze global glycoprotein abundance and glycosylation occupancy for proteins from high-grade ovarian serous carcinoma (HGSC) and serous cystadenoma, a benign epithelial ovarian tumor, by using LC-MS/MS-based technique. 28491011 5 134 theme glycosylation 568:580 arg1 occupancy 582:590 protein glycosylation occupancy 560:590 protein glycosylation occupancy 560:590 In addition to glycoprotein expressions, the analysis of protein glycosylation occupancy could be important for the understanding of cancer biology as well as the identification of potential glycoprotein changes in cancer. 28491011 1 135 theme survival 257:264 arg1 rate 266:269 a poor 5-year survival rate 243:269 a poor 5-year survival rate 243:269 BACKGROUND Epithelial ovarian carcinomas encompass a heterogeneous group of diseases with a poor 5-year survival rate. 28491011 0 136 from tumors 145:150 arg1 occupancy 90:98 glycosylation occupancy 76:98 glycosylation occupancy from benign and malignant epithelial ovarian tumors 76:150 An integrated proteomic and glycoproteomic approach uncovers differences in glycosylation occupancy from benign and malignant epithelial ovarian tumors. 28491011 0 136 from tumors 145:150 arg1 differences 61:71 differences 61:71 differences in glycosylation occupancy from benign and malignant epithelial ovarian tumors 61:150 An integrated proteomic and glycoproteomic approach uncovers differences in glycosylation occupancy from benign and malignant epithelial ovarian tumors. 28491011 10 137 theme unique 1739:1744 arg1 changes 1746:1752 unique changes 1739:1752 unique changes in glycosylation occupancies rather than the protein expression levels 1739:1823 The glycosite-containing peptides with unique changes in glycosylation occupancies rather than the protein expression levels were identified. 28491011 5 138 from cancer 718:723 arg1 identification 666:679 the identification 662:679 cancer biology as well as the identification of potential glycoprotein changes in cancer 636:723 In addition to glycoprotein expressions, the analysis of protein glycosylation occupancy could be important for the understanding of cancer biology as well as the identification of potential glycoprotein changes in cancer. 28491011 5 138 from cancer 718:723 arg1 biology 643:649 cancer biology 636:649 cancer biology as well as the identification of potential glycoprotein changes in cancer 636:723 In addition to glycoprotein expressions, the analysis of protein glycosylation occupancy could be important for the understanding of cancer biology as well as the identification of potential glycoprotein changes in cancer. 24596091 9 0 theme S-layer 1606:1612 arg1 glycoprotein 1614:1625 the H. volcanii S-layer glycoprotein 1590:1625 the H. volcanii S-layer glycoprotein 1590:1625 This work describes a novel N-linked oligosaccharide containing a repeating SQ-Hex unit bound to Asn-732 of the H. volcanii S-layer glycoprotein, a position that had not been reported as glycosylated. 24596091 9 0 theme S-layer 1606:1612 arg1 position 1630:1637 a position 1628:1637 a position that had not been reported as glycosylated 1628:1680 This work describes a novel N-linked oligosaccharide containing a repeating SQ-Hex unit bound to Asn-732 of the H. volcanii S-layer glycoprotein, a position that had not been reported as glycosylated. 24596091 7 1 theme Mass 1077:1080 arg1 analysis 1095:1102 Mass spectrometry analysis 1077:1102 Mass spectrometry analysis 1077:1102 Mass spectrometry analysis showed that the wild type glycoprotein released a novel oligosaccharide species corresponding to GlcNAc-GlcNAc(Hex)2-(SQ-Hex)6 in contrast to the mutant protein, which contained the shorter form GlcNAc2(Hex)2-SQ-Hex-SQ. 24596091 9 2 link N-linked 1510:1517 arg1 oligosaccharide 1519:1533 a novel N-linked oligosaccharide 1502:1533 a novel N-linked oligosaccharide containing a repeating SQ-Hex unit bound to Asn-732 of the H. volcanii S-layer glycoprotein, a position that had not been reported as glycosylated 1502:1680 This work describes a novel N-linked oligosaccharide containing a repeating SQ-Hex unit bound to Asn-732 of the H. volcanii S-layer glycoprotein, a position that had not been reported as glycosylated. 24596091 7 3 theme mutant 1250:1255 arg1 protein 1257:1263 the mutant protein 1246:1263 the mutant protein 1246:1263 Mass spectrometry analysis showed that the wild type glycoprotein released a novel oligosaccharide species corresponding to GlcNAc-GlcNAc(Hex)2-(SQ-Hex)6 in contrast to the mutant protein, which contained the shorter form GlcNAc2(Hex)2-SQ-Hex-SQ. 24596091 9 4 contain containing 1535:1544 arg2 unit 1565:1568 a repeating SQ-Hex unit 1546:1568 a repeating SQ-Hex unit bound to Asn-732 of the H. volcanii S-layer glycoprotein, a position that had not been reported as glycosylated 1546:1680 This work describes a novel N-linked oligosaccharide containing a repeating SQ-Hex unit bound to Asn-732 of the H. volcanii S-layer glycoprotein, a position that had not been reported as glycosylated. 24596091 9 4 contain containing 1535:1544 arg1 oligosaccharide 1519:1533 a novel N-linked oligosaccharide 1502:1533 a novel N-linked oligosaccharide containing a repeating SQ-Hex unit bound to Asn-732 of the H. volcanii S-layer glycoprotein, a position that had not been reported as glycosylated 1502:1680 This work describes a novel N-linked oligosaccharide containing a repeating SQ-Hex unit bound to Asn-732 of the H. volcanii S-layer glycoprotein, a position that had not been reported as glycosylated. 24596091 1 5 from biology 267:273 arg1 Archaea 295:301 Archaea 295:301 Archaea 295:301 Rhomboid proteases occur in all domains of life; however, their physiological role is not completely understood, and nothing is known of the biology of these enzymes in Archaea. 24596091 8 6 gly glycopeptide 1368:1379 arg2 glycopeptide 1368:1379 the wild type glycopeptide fraction 1354:1388 the wild type glycopeptide fraction 1354:1388 A glycoproteomics approach of the wild type glycopeptide fraction revealed Asn-732 peptide fragments linked to the sulfoquinovose-containing oligosaccharide. 24596091 5 7 used used 805:808 arg2 model 815:819 a model 813:819 a model to study haloarchaeal protein N-glycosylation 813:865 The H. volcanii S-layer glycoprotein has been extensively used as a model to study haloarchaeal protein N-glycosylation. 24596091 5 7 used used 805:808 arg2 glycoprotein 771:782 The H. volcanii S-layer glycoprotein 747:782 The H. volcanii S-layer glycoprotein 747:782 The H. volcanii S-layer glycoprotein has been extensively used as a model to study haloarchaeal protein N-glycosylation. 24596091 7 8 from 6 1229:1229 arg1 contrast 1234:1241 contrast 1234:1241 contrast to the mutant protein, which contained the shorter form GlcNAc2(Hex)2-SQ-Hex-SQ 1234:1321 Mass spectrometry analysis showed that the wild type glycoprotein released a novel oligosaccharide species corresponding to GlcNAc-GlcNAc(Hex)2-(SQ-Hex)6 in contrast to the mutant protein, which contained the shorter form GlcNAc2(Hex)2-SQ-Hex-SQ. 24596091 0 9 gly glycoprotein 90:101 arg1 glycoprotein 90:101 the S-layer glycoprotein 78:101 the S-layer glycoprotein of Haloferax volcanii 78:123 A rhomboid protease gene deletion affects a novel oligosaccharide N-linked to the S-layer glycoprotein of Haloferax volcanii. 24596091 0 10 theme volcanii 116:123 arg1 glycoprotein 90:101 the S-layer glycoprotein 78:101 the S-layer glycoprotein of Haloferax volcanii 78:123 A rhomboid protease gene deletion affects a novel oligosaccharide N-linked to the S-layer glycoprotein of Haloferax volcanii. 24596091 5 11 theme S-layer 763:769 arg1 glycoprotein 771:782 The H. volcanii S-layer glycoprotein 747:782 The H. volcanii S-layer glycoprotein 747:782 The H. volcanii S-layer glycoprotein has been extensively used as a model to study haloarchaeal protein N-glycosylation. 24596091 5 11 theme S-layer 763:769 arg1 model 815:819 a model 813:819 a model to study haloarchaeal protein N-glycosylation 813:865 The H. volcanii S-layer glycoprotein has been extensively used as a model to study haloarchaeal protein N-glycosylation. 24596091 8 12 theme type 1363:1366 arg1 fraction 1381:1388 the wild type glycopeptide fraction 1354:1388 the wild type glycopeptide fraction 1354:1388 A glycoproteomics approach of the wild type glycopeptide fraction revealed Asn-732 peptide fragments linked to the sulfoquinovose-containing oligosaccharide. 24596091 7 13 theme Hex 1307:1309 arg1 2-SQ-Hex-SQ 1311:1321 the shorter form GlcNAc2(Hex)2-SQ-Hex-SQ 1282:1321 the shorter form GlcNAc2(Hex)2-SQ-Hex-SQ 1282:1321 Mass spectrometry analysis showed that the wild type glycoprotein released a novel oligosaccharide species corresponding to GlcNAc-GlcNAc(Hex)2-(SQ-Hex)6 in contrast to the mutant protein, which contained the shorter form GlcNAc2(Hex)2-SQ-Hex-SQ. 24596091 3 14 theme mutant 522:527 arg1 MIG1 537:540 MIG1 537:540 MIG1 537:540 Chromosomal deletion of rhoII was successful, indicating that this gene is not essential for this organism; however, the mutant strain (MIG1) showed reduced motility and increased sensitivity to novobiocin. 24596091 3 14 theme mutant 522:527 arg1 strain 529:534 the mutant strain 518:534 the mutant strain (MIG1) 518:541 Chromosomal deletion of rhoII was successful, indicating that this gene is not essential for this organism; however, the mutant strain (MIG1) showed reduced motility and increased sensitivity to novobiocin. 24596091 8 15 theme fraction 1381:1388 arg1 approach 1342:1349 A glycoproteomics approach 1324:1349 A glycoproteomics approach of the wild type glycopeptide fraction 1324:1388 A glycoproteomics approach of the wild type glycopeptide fraction revealed Asn-732 peptide fragments linked to the sulfoquinovose-containing oligosaccharide. 24596091 7 16 theme GlcNAc2 1299:1305 arg1 2-SQ-Hex-SQ 1311:1321 the shorter form GlcNAc2(Hex)2-SQ-Hex-SQ 1282:1321 the shorter form GlcNAc2(Hex)2-SQ-Hex-SQ 1282:1321 Mass spectrometry analysis showed that the wild type glycoprotein released a novel oligosaccharide species corresponding to GlcNAc-GlcNAc(Hex)2-(SQ-Hex)6 in contrast to the mutant protein, which contained the shorter form GlcNAc2(Hex)2-SQ-Hex-SQ. 24596091 5 17 theme protein 843:849 arg1 N-glycosylation 851:865 haloarchaeal protein N-glycosylation 830:865 haloarchaeal protein N-glycosylation 830:865 The H. volcanii S-layer glycoprotein has been extensively used as a model to study haloarchaeal protein N-glycosylation. 24596091 6 18 theme HPLC 868:871 arg1 analysis 873:880 HPLC analysis 868:880 HPLC analysis of oligosaccharides released from the S-layer glycoprotein after PNGase treatment 868:962 HPLC analysis of oligosaccharides released from the S-layer glycoprotein after PNGase treatment revealed that MIG1 was enriched in species with lower retention times than those derived from the parent strain. 24596091 8 19 theme Asn-732 1399:1405 arg1 fragments 1415:1423 Asn-732 peptide fragments 1399:1423 Asn-732 peptide fragments linked to the sulfoquinovose-containing oligosaccharide 1399:1479 A glycoproteomics approach of the wild type glycopeptide fraction revealed Asn-732 peptide fragments linked to the sulfoquinovose-containing oligosaccharide. 24596091 7 20 theme shorter 1286:1292 arg1 2-SQ-Hex-SQ 1311:1321 the shorter form GlcNAc2(Hex)2-SQ-Hex-SQ 1282:1321 the shorter form GlcNAc2(Hex)2-SQ-Hex-SQ 1282:1321 Mass spectrometry analysis showed that the wild type glycoprotein released a novel oligosaccharide species corresponding to GlcNAc-GlcNAc(Hex)2-(SQ-Hex)6 in contrast to the mutant protein, which contained the shorter form GlcNAc2(Hex)2-SQ-Hex-SQ. 24596091 4 21 theme Membrane 608:615 arg1 preparations 617:628 Membrane preparations 608:628 Membrane preparations of MIG1 608:636 Membrane preparations of MIG1 were enriched in two glycoproteins, identified as the S-layer glycoprotein and an ABC transporter component. 24596091 7 22 theme GlcNAc-GlcNAc 1201:1213 arg1 SQ-Hex 1222:1227 SQ-Hex 1222:1227 SQ-Hex 1222:1227 Mass spectrometry analysis showed that the wild type glycoprotein released a novel oligosaccharide species corresponding to GlcNAc-GlcNAc(Hex)2-(SQ-Hex)6 in contrast to the mutant protein, which contained the shorter form GlcNAc2(Hex)2-SQ-Hex-SQ. 24596091 7 22 theme GlcNAc-GlcNAc 1201:1213 arg1 Hex 1215:1217 GlcNAc-GlcNAc(Hex)2- 1201:1220 GlcNAc-GlcNAc(Hex)2-(SQ-Hex)6 in contrast to the mutant protein, which contained the shorter form GlcNAc2(Hex)2-SQ-Hex-SQ 1201:1321 Mass spectrometry analysis showed that the wild type glycoprotein released a novel oligosaccharide species corresponding to GlcNAc-GlcNAc(Hex)2-(SQ-Hex)6 in contrast to the mutant protein, which contained the shorter form GlcNAc2(Hex)2-SQ-Hex-SQ. 24596091 0 23 theme protease 11:18 arg1 deletion 25:32 A rhomboid protease gene deletion 0:32 A rhomboid protease gene deletion 0:32 A rhomboid protease gene deletion affects a novel oligosaccharide N-linked to the S-layer glycoprotein of Haloferax volcanii. 24596091 4 24 gly glycoprotein 700:711 arg1 glycoprotein 700:711 the S-layer glycoprotein 688:711 the S-layer glycoprotein 688:711 Membrane preparations of MIG1 were enriched in two glycoproteins, identified as the S-layer glycoprotein and an ABC transporter component. 24596091 6 25 theme PNGase 947:952 arg1 treatment 954:962 PNGase treatment 947:962 PNGase treatment 947:962 HPLC analysis of oligosaccharides released from the S-layer glycoprotein after PNGase treatment revealed that MIG1 was enriched in species with lower retention times than those derived from the parent strain. 24596091 8 26 theme sulfoquinovose-containing 1439:1463 arg1 oligosaccharide 1465:1479 the sulfoquinovose-containing oligosaccharide 1435:1479 the sulfoquinovose-containing oligosaccharide 1435:1479 A glycoproteomics approach of the wild type glycopeptide fraction revealed Asn-732 peptide fragments linked to the sulfoquinovose-containing oligosaccharide. 24596091 0 27 theme S-layer 82:88 arg1 glycoprotein 90:101 the S-layer glycoprotein 78:101 the S-layer glycoprotein of Haloferax volcanii 78:123 A rhomboid protease gene deletion affects a novel oligosaccharide N-linked to the S-layer glycoprotein of Haloferax volcanii. 24596091 9 28 theme novel 1504:1508 arg1 oligosaccharide 1519:1533 a novel N-linked oligosaccharide 1502:1533 a novel N-linked oligosaccharide containing a repeating SQ-Hex unit bound to Asn-732 of the H. volcanii S-layer glycoprotein, a position that had not been reported as glycosylated 1502:1680 This work describes a novel N-linked oligosaccharide containing a repeating SQ-Hex unit bound to Asn-732 of the H. volcanii S-layer glycoprotein, a position that had not been reported as glycosylated. 24596091 2 29 theme finger 386:391 arg1 domain 393:398 a zinc finger domain 379:398 a zinc finger domain 379:398 One of the two rhomboid homologs of Haloferax volcanii (RhoII) is fused to a zinc finger domain. 24596091 2 30 theme Haloferax 340:348 arg1 volcanii 350:357 Haloferax volcanii 340:357 Haloferax volcanii (RhoII) 340:365 One of the two rhomboid homologs of Haloferax volcanii (RhoII) is fused to a zinc finger domain. 24596091 2 30 theme Haloferax 340:348 arg1 RhoII 360:364 RhoII 360:364 RhoII 360:364 One of the two rhomboid homologs of Haloferax volcanii (RhoII) is fused to a zinc finger domain. 24596091 7 31 dep Hex 1215:1217 arg1 6 1229:1229 6 1229:1229 6 1229:1229 Mass spectrometry analysis showed that the wild type glycoprotein released a novel oligosaccharide species corresponding to GlcNAc-GlcNAc(Hex)2-(SQ-Hex)6 in contrast to the mutant protein, which contained the shorter form GlcNAc2(Hex)2-SQ-Hex-SQ. 24596091 6 32 theme lower 1012:1016 arg1 times 1028:1032 lower retention times 1012:1032 lower retention times than those derived from the parent strain 1012:1074 HPLC analysis of oligosaccharides released from the S-layer glycoprotein after PNGase treatment revealed that MIG1 was enriched in species with lower retention times than those derived from the parent strain. 24596091 3 33 theme Chromosomal 401:411 arg1 deletion 413:420 Chromosomal deletion 401:420 Chromosomal deletion of rhoII 401:429 Chromosomal deletion of rhoII was successful, indicating that this gene is not essential for this organism; however, the mutant strain (MIG1) showed reduced motility and increased sensitivity to novobiocin. 24596091 7 34 theme wild 1120:1123 arg1 type 1125:1128 the wild type 1116:1128 the wild type glycoprotein 1116:1141 Mass spectrometry analysis showed that the wild type glycoprotein released a novel oligosaccharide species corresponding to GlcNAc-GlcNAc(Hex)2-(SQ-Hex)6 in contrast to the mutant protein, which contained the shorter form GlcNAc2(Hex)2-SQ-Hex-SQ. 24596091 4 35 gly glycoproteins 659:671 arg1 glycoproteins 659:671 two glycoproteins 655:671 two glycoproteins 655:671 Membrane preparations of MIG1 were enriched in two glycoproteins, identified as the S-layer glycoprotein and an ABC transporter component. 24596091 9 36 theme SQ-Hex 1558:1563 arg1 unit 1565:1568 a repeating SQ-Hex unit 1546:1568 a repeating SQ-Hex unit bound to Asn-732 of the H. volcanii S-layer glycoprotein, a position that had not been reported as glycosylated 1546:1680 This work describes a novel N-linked oligosaccharide containing a repeating SQ-Hex unit bound to Asn-732 of the H. volcanii S-layer glycoprotein, a position that had not been reported as glycosylated. 24596091 6 37 attach derived 1045:1051 arg2 those 1039:1043 those 1039:1043 those 1039:1043 HPLC analysis of oligosaccharides released from the S-layer glycoprotein after PNGase treatment revealed that MIG1 was enriched in species with lower retention times than those derived from the parent strain. 24596091 6 37 attach derived 1045:1051 arg1 strain 1069:1074 the parent strain 1058:1074 the parent strain 1058:1074 HPLC analysis of oligosaccharides released from the S-layer glycoprotein after PNGase treatment revealed that MIG1 was enriched in species with lower retention times than those derived from the parent strain. 24596091 8 38 theme glycoproteomics 1326:1340 arg1 approach 1342:1349 A glycoproteomics approach 1324:1349 A glycoproteomics approach of the wild type glycopeptide fraction 1324:1388 A glycoproteomics approach of the wild type glycopeptide fraction revealed Asn-732 peptide fragments linked to the sulfoquinovose-containing oligosaccharide. 24596091 1 39 theme enzymes 284:290 arg1 biology 267:273 the biology 263:273 the biology of these enzymes in Archaea 263:301 Rhomboid proteases occur in all domains of life; however, their physiological role is not completely understood, and nothing is known of the biology of these enzymes in Archaea. 24596091 0 40 link N-linked 66:73 arg1 oligosaccharide 50:64 a novel oligosaccharide 42:64 a novel oligosaccharide N-linked to the S-layer glycoprotein of Haloferax volcanii 42:123 A rhomboid protease gene deletion affects a novel oligosaccharide N-linked to the S-layer glycoprotein of Haloferax volcanii. 24596091 7 41 gly glycoprotein 1130:1141 arg1 glycoprotein 1130:1141 the wild type glycoprotein 1116:1141 the wild type glycoprotein 1116:1141 Mass spectrometry analysis showed that the wild type glycoprotein released a novel oligosaccharide species corresponding to GlcNAc-GlcNAc(Hex)2-(SQ-Hex)6 in contrast to the mutant protein, which contained the shorter form GlcNAc2(Hex)2-SQ-Hex-SQ. 24596091 5 42 theme H. 751:752 arg1 glycoprotein 771:782 The H. volcanii S-layer glycoprotein 747:782 The H. volcanii S-layer glycoprotein 747:782 The H. volcanii S-layer glycoprotein has been extensively used as a model to study haloarchaeal protein N-glycosylation. 24596091 5 42 theme H. 751:752 arg1 model 815:819 a model 813:819 a model to study haloarchaeal protein N-glycosylation 813:865 The H. volcanii S-layer glycoprotein has been extensively used as a model to study haloarchaeal protein N-glycosylation. 24596091 6 43 theme parent 1062:1067 arg1 strain 1069:1074 the parent strain 1058:1074 the parent strain 1058:1074 HPLC analysis of oligosaccharides released from the S-layer glycoprotein after PNGase treatment revealed that MIG1 was enriched in species with lower retention times than those derived from the parent strain. 24596091 8 44 theme wild 1358:1361 arg1 fraction 1381:1388 the wild type glycopeptide fraction 1354:1388 the wild type glycopeptide fraction 1354:1388 A glycoproteomics approach of the wild type glycopeptide fraction revealed Asn-732 peptide fragments linked to the sulfoquinovose-containing oligosaccharide. 24596091 2 45 theme homologs 328:335 arg1 One 304:306 One 304:306 One 304:306 One of the two rhomboid homologs of Haloferax volcanii (RhoII) is fused to a zinc finger domain. 24596091 2 45 theme homologs 328:335 arg1 homologs 328:335 the two rhomboid homologs 311:335 the two rhomboid homologs of Haloferax volcanii (RhoII) 311:365 One of the two rhomboid homologs of Haloferax volcanii (RhoII) is fused to a zinc finger domain. 24596091 1 46 theme life 169:172 arg1 life 169:172 life 169:172 life 169:172 Rhomboid proteases occur in all domains of life; however, their physiological role is not completely understood, and nothing is known of the biology of these enzymes in Archaea. 24596091 1 46 theme life 169:172 arg1 domains 158:164 all domains 154:164 all domains of life 154:172 Rhomboid proteases occur in all domains of life; however, their physiological role is not completely understood, and nothing is known of the biology of these enzymes in Archaea. 24596091 7 47 theme spectrometry 1082:1093 arg1 analysis 1095:1102 Mass spectrometry analysis 1077:1102 Mass spectrometry analysis 1077:1102 Mass spectrometry analysis showed that the wild type glycoprotein released a novel oligosaccharide species corresponding to GlcNAc-GlcNAc(Hex)2-(SQ-Hex)6 in contrast to the mutant protein, which contained the shorter form GlcNAc2(Hex)2-SQ-Hex-SQ. 24596091 9 48 theme glycoprotein 1614:1625 arg1 Asn-732 1579:1585 Asn-732 1579:1585 Asn-732 of the H. volcanii S-layer glycoprotein, a position that had not been reported as glycosylated 1579:1680 This work describes a novel N-linked oligosaccharide containing a repeating SQ-Hex unit bound to Asn-732 of the H. volcanii S-layer glycoprotein, a position that had not been reported as glycosylated. 24596091 3 49 theme reduced 550:556 arg1 motility 558:565 reduced motility 550:565 reduced motility 550:565 Chromosomal deletion of rhoII was successful, indicating that this gene is not essential for this organism; however, the mutant strain (MIG1) showed reduced motility and increased sensitivity to novobiocin. 24596091 10 50 theme first 1720:1724 arg1 insight 1726:1732 the first insight 1716:1732 the first insight on the biological role of rhomboid proteases in Archaea 1716:1788 Furthermore, this study provides the first insight on the biological role of rhomboid proteases in Archaea, suggesting a link between protein glycosylation and this protease family. 24596091 8 51 attach linked 1425:1430 arg1 oligosaccharide 1465:1479 the sulfoquinovose-containing oligosaccharide 1435:1479 the sulfoquinovose-containing oligosaccharide 1435:1479 A glycoproteomics approach of the wild type glycopeptide fraction revealed Asn-732 peptide fragments linked to the sulfoquinovose-containing oligosaccharide. 24596091 8 51 attach linked 1425:1430 arg2 fragments 1415:1423 Asn-732 peptide fragments 1399:1423 Asn-732 peptide fragments linked to the sulfoquinovose-containing oligosaccharide 1399:1479 A glycoproteomics approach of the wild type glycopeptide fraction revealed Asn-732 peptide fragments linked to the sulfoquinovose-containing oligosaccharide. 24596091 10 52 theme biological 1741:1750 arg1 role 1752:1755 the biological role 1737:1755 the biological role of rhomboid proteases in Archaea 1737:1788 Furthermore, this study provides the first insight on the biological role of rhomboid proteases in Archaea, suggesting a link between protein glycosylation and this protease family. 24596091 6 53 theme S-layer 920:926 arg1 glycoprotein 928:939 the S-layer glycoprotein 916:939 the S-layer glycoprotein 916:939 HPLC analysis of oligosaccharides released from the S-layer glycoprotein after PNGase treatment revealed that MIG1 was enriched in species with lower retention times than those derived from the parent strain. 24596091 5 54 gly glycoprotein 771:782 arg1 glycoprotein 771:782 The H. volcanii S-layer glycoprotein 747:782 The H. volcanii S-layer glycoprotein 747:782 The H. volcanii S-layer glycoprotein has been extensively used as a model to study haloarchaeal protein N-glycosylation. 24596091 5 54 gly glycoprotein 771:782 arg1 model 815:819 a model 813:819 a model to study haloarchaeal protein N-glycosylation 813:865 The H. volcanii S-layer glycoprotein has been extensively used as a model to study haloarchaeal protein N-glycosylation. 24596091 8 55 theme glycopeptide 1368:1379 arg1 fraction 1381:1388 the wild type glycopeptide fraction 1354:1388 the wild type glycopeptide fraction 1354:1388 A glycoproteomics approach of the wild type glycopeptide fraction revealed Asn-732 peptide fragments linked to the sulfoquinovose-containing oligosaccharide. 24596091 10 56 theme proteases 1769:1777 arg1 role 1752:1755 the biological role 1737:1755 the biological role of rhomboid proteases in Archaea 1737:1788 Furthermore, this study provides the first insight on the biological role of rhomboid proteases in Archaea, suggesting a link between protein glycosylation and this protease family. 24596091 1 57 theme physiological 190:202 arg1 role 204:207 their physiological role 184:207 their physiological role 184:207 Rhomboid proteases occur in all domains of life; however, their physiological role is not completely understood, and nothing is known of the biology of these enzymes in Archaea. 24596091 6 58 theme oligosaccharides 885:900 arg1 analysis 873:880 HPLC analysis 868:880 HPLC analysis of oligosaccharides released from the S-layer glycoprotein after PNGase treatment 868:962 HPLC analysis of oligosaccharides released from the S-layer glycoprotein after PNGase treatment revealed that MIG1 was enriched in species with lower retention times than those derived from the parent strain. 24596091 5 59 theme haloarchaeal 830:841 arg1 N-glycosylation 851:865 haloarchaeal protein N-glycosylation 830:865 haloarchaeal protein N-glycosylation 830:865 The H. volcanii S-layer glycoprotein has been extensively used as a model to study haloarchaeal protein N-glycosylation. 24596091 8 60 theme peptide 1407:1413 arg1 fragments 1415:1423 Asn-732 peptide fragments 1399:1423 Asn-732 peptide fragments linked to the sulfoquinovose-containing oligosaccharide 1399:1479 A glycoproteomics approach of the wild type glycopeptide fraction revealed Asn-732 peptide fragments linked to the sulfoquinovose-containing oligosaccharide. 24596091 4 61 theme MIG1 633:636 arg1 preparations 617:628 Membrane preparations 608:628 Membrane preparations of MIG1 608:636 Membrane preparations of MIG1 were enriched in two glycoproteins, identified as the S-layer glycoprotein and an ABC transporter component. 24596091 1 62 theme Rhomboid 126:133 arg1 proteases 135:143 Rhomboid proteases 126:143 Rhomboid proteases 126:143 Rhomboid proteases occur in all domains of life; however, their physiological role is not completely understood, and nothing is known of the biology of these enzymes in Archaea. 24596091 7 63 theme form 1294:1297 arg1 2-SQ-Hex-SQ 1311:1321 the shorter form GlcNAc2(Hex)2-SQ-Hex-SQ 1282:1321 the shorter form GlcNAc2(Hex)2-SQ-Hex-SQ 1282:1321 Mass spectrometry analysis showed that the wild type glycoprotein released a novel oligosaccharide species corresponding to GlcNAc-GlcNAc(Hex)2-(SQ-Hex)6 in contrast to the mutant protein, which contained the shorter form GlcNAc2(Hex)2-SQ-Hex-SQ. 24596091 0 64 theme N-linked 66:73 arg1 oligosaccharide 50:64 a novel oligosaccharide 42:64 a novel oligosaccharide N-linked to the S-layer glycoprotein of Haloferax volcanii 42:123 A rhomboid protease gene deletion affects a novel oligosaccharide N-linked to the S-layer glycoprotein of Haloferax volcanii. 24596091 6 65 attach released 902:909 arg1 glycoprotein 928:939 the S-layer glycoprotein 916:939 the S-layer glycoprotein 916:939 HPLC analysis of oligosaccharides released from the S-layer glycoprotein after PNGase treatment revealed that MIG1 was enriched in species with lower retention times than those derived from the parent strain. 24596091 6 65 attach released 902:909 arg2 oligosaccharides 885:900 oligosaccharides 885:900 oligosaccharides released from the S-layer glycoprotein after PNGase treatment 885:962 HPLC analysis of oligosaccharides released from the S-layer glycoprotein after PNGase treatment revealed that MIG1 was enriched in species with lower retention times than those derived from the parent strain. 24596091 7 66 theme oligosaccharide 1160:1174 arg1 species 1176:1182 a novel oligosaccharide species 1152:1182 a novel oligosaccharide species corresponding to GlcNAc-GlcNAc(Hex)2-(SQ-Hex)6 in contrast to the mutant protein, which contained the shorter form GlcNAc2(Hex)2-SQ-Hex-SQ 1152:1321 Mass spectrometry analysis showed that the wild type glycoprotein released a novel oligosaccharide species corresponding to GlcNAc-GlcNAc(Hex)2-(SQ-Hex)6 in contrast to the mutant protein, which contained the shorter form GlcNAc2(Hex)2-SQ-Hex-SQ. 24596091 10 67 from insight 1726:1732 arg1 role 1752:1755 the biological role 1737:1755 the biological role of rhomboid proteases in Archaea 1737:1788 Furthermore, this study provides the first insight on the biological role of rhomboid proteases in Archaea, suggesting a link between protein glycosylation and this protease family. 24596091 7 68 theme novel 1154:1158 arg1 species 1176:1182 a novel oligosaccharide species 1152:1182 a novel oligosaccharide species corresponding to GlcNAc-GlcNAc(Hex)2-(SQ-Hex)6 in contrast to the mutant protein, which contained the shorter form GlcNAc2(Hex)2-SQ-Hex-SQ 1152:1321 Mass spectrometry analysis showed that the wild type glycoprotein released a novel oligosaccharide species corresponding to GlcNAc-GlcNAc(Hex)2-(SQ-Hex)6 in contrast to the mutant protein, which contained the shorter form GlcNAc2(Hex)2-SQ-Hex-SQ. 24596091 0 69 theme Haloferax 106:114 arg1 volcanii 116:123 Haloferax volcanii 106:123 Haloferax volcanii 106:123 A rhomboid protease gene deletion affects a novel oligosaccharide N-linked to the S-layer glycoprotein of Haloferax volcanii. 24596091 9 70 theme N-linked 1510:1517 arg1 oligosaccharide 1519:1533 a novel N-linked oligosaccharide 1502:1533 a novel N-linked oligosaccharide containing a repeating SQ-Hex unit bound to Asn-732 of the H. volcanii S-layer glycoprotein, a position that had not been reported as glycosylated 1502:1680 This work describes a novel N-linked oligosaccharide containing a repeating SQ-Hex unit bound to Asn-732 of the H. volcanii S-layer glycoprotein, a position that had not been reported as glycosylated. 24596091 10 71 from role 1752:1755 arg1 Archaea 1782:1788 Archaea 1782:1788 Archaea 1782:1788 Furthermore, this study provides the first insight on the biological role of rhomboid proteases in Archaea, suggesting a link between protein glycosylation and this protease family. 24596091 4 72 theme S-layer 692:698 arg1 glycoprotein 700:711 the S-layer glycoprotein 688:711 the S-layer glycoprotein 688:711 Membrane preparations of MIG1 were enriched in two glycoproteins, identified as the S-layer glycoprotein and an ABC transporter component. 24596091 2 73 theme volcanii 350:357 arg1 homologs 328:335 the two rhomboid homologs 311:335 the two rhomboid homologs of Haloferax volcanii (RhoII) 311:365 One of the two rhomboid homologs of Haloferax volcanii (RhoII) is fused to a zinc finger domain. 24596091 0 74 theme rhomboid 2:9 arg1 deletion 25:32 A rhomboid protease gene deletion 0:32 A rhomboid protease gene deletion 0:32 A rhomboid protease gene deletion affects a novel oligosaccharide N-linked to the S-layer glycoprotein of Haloferax volcanii. 24596091 6 75 theme retention 1018:1026 arg1 times 1028:1032 lower retention times 1012:1032 lower retention times than those derived from the parent strain 1012:1074 HPLC analysis of oligosaccharides released from the S-layer glycoprotein after PNGase treatment revealed that MIG1 was enriched in species with lower retention times than those derived from the parent strain. 24596091 2 76 theme zinc 381:384 arg1 domain 393:398 a zinc finger domain 379:398 a zinc finger domain 379:398 One of the two rhomboid homologs of Haloferax volcanii (RhoII) is fused to a zinc finger domain. 24596091 0 77 theme gene 20:23 arg1 deletion 25:32 A rhomboid protease gene deletion 0:32 A rhomboid protease gene deletion 0:32 A rhomboid protease gene deletion affects a novel oligosaccharide N-linked to the S-layer glycoprotein of Haloferax volcanii. 24596091 4 78 theme transporter 724:734 arg1 component 736:744 an ABC transporter component 717:744 an ABC transporter component 717:744 Membrane preparations of MIG1 were enriched in two glycoproteins, identified as the S-layer glycoprotein and an ABC transporter component. 24596091 9 79 theme repeating 1548:1556 arg1 unit 1565:1568 a repeating SQ-Hex unit 1546:1568 a repeating SQ-Hex unit bound to Asn-732 of the H. volcanii S-layer glycoprotein, a position that had not been reported as glycosylated 1546:1680 This work describes a novel N-linked oligosaccharide containing a repeating SQ-Hex unit bound to Asn-732 of the H. volcanii S-layer glycoprotein, a position that had not been reported as glycosylated. 24596091 10 80 theme protein 1817:1823 arg1 glycosylation 1825:1837 protein glycosylation 1817:1837 protein glycosylation 1817:1837 Furthermore, this study provides the first insight on the biological role of rhomboid proteases in Archaea, suggesting a link between protein glycosylation and this protease family. 24596091 0 81 theme novel 44:48 arg1 oligosaccharide 50:64 a novel oligosaccharide 42:64 a novel oligosaccharide N-linked to the S-layer glycoprotein of Haloferax volcanii 42:123 A rhomboid protease gene deletion affects a novel oligosaccharide N-linked to the S-layer glycoprotein of Haloferax volcanii. 24596091 2 82 theme rhomboid 319:326 arg1 homologs 328:335 the two rhomboid homologs 311:335 the two rhomboid homologs of Haloferax volcanii (RhoII) 311:365 One of the two rhomboid homologs of Haloferax volcanii (RhoII) is fused to a zinc finger domain. 24596091 10 83 theme protease 1848:1855 arg1 family 1857:1862 this protease family 1843:1862 this protease family 1843:1862 Furthermore, this study provides the first insight on the biological role of rhomboid proteases in Archaea, suggesting a link between protein glycosylation and this protease family. 24596091 6 84 gly glycoprotein 928:939 arg1 glycoprotein 928:939 the S-layer glycoprotein 916:939 the S-layer glycoprotein 916:939 HPLC analysis of oligosaccharides released from the S-layer glycoprotein after PNGase treatment revealed that MIG1 was enriched in species with lower retention times than those derived from the parent strain. 24596091 9 85 gly glycoprotein 1614:1625 arg1 glycoprotein 1614:1625 the H. volcanii S-layer glycoprotein 1590:1625 the H. volcanii S-layer glycoprotein 1590:1625 This work describes a novel N-linked oligosaccharide containing a repeating SQ-Hex unit bound to Asn-732 of the H. volcanii S-layer glycoprotein, a position that had not been reported as glycosylated. 24596091 9 85 gly glycoprotein 1614:1625 arg1 position 1630:1637 a position 1628:1637 a position that had not been reported as glycosylated 1628:1680 This work describes a novel N-linked oligosaccharide containing a repeating SQ-Hex unit bound to Asn-732 of the H. volcanii S-layer glycoprotein, a position that had not been reported as glycosylated. 24596091 10 86 theme rhomboid 1760:1767 arg1 proteases 1769:1777 rhomboid proteases 1760:1777 rhomboid proteases 1760:1777 Furthermore, this study provides the first insight on the biological role of rhomboid proteases in Archaea, suggesting a link between protein glycosylation and this protease family. 24596091 3 87 theme increased 571:579 arg1 sensitivity 581:591 increased sensitivity 571:591 increased sensitivity to novobiocin 571:605 Chromosomal deletion of rhoII was successful, indicating that this gene is not essential for this organism; however, the mutant strain (MIG1) showed reduced motility and increased sensitivity to novobiocin. 24596091 3 88 theme rhoII 425:429 arg1 deletion 413:420 Chromosomal deletion 401:420 Chromosomal deletion of rhoII 401:429 Chromosomal deletion of rhoII was successful, indicating that this gene is not essential for this organism; however, the mutant strain (MIG1) showed reduced motility and increased sensitivity to novobiocin. 24596091 7 89 contain contained 1272:1280 arg1 protein 1257:1263 the mutant protein 1246:1263 the mutant protein 1246:1263 Mass spectrometry analysis showed that the wild type glycoprotein released a novel oligosaccharide species corresponding to GlcNAc-GlcNAc(Hex)2-(SQ-Hex)6 in contrast to the mutant protein, which contained the shorter form GlcNAc2(Hex)2-SQ-Hex-SQ. 24596091 7 89 contain contained 1272:1280 arg2 2-SQ-Hex-SQ 1311:1321 the shorter form GlcNAc2(Hex)2-SQ-Hex-SQ 1282:1321 the shorter form GlcNAc2(Hex)2-SQ-Hex-SQ 1282:1321 Mass spectrometry analysis showed that the wild type glycoprotein released a novel oligosaccharide species corresponding to GlcNAc-GlcNAc(Hex)2-(SQ-Hex)6 in contrast to the mutant protein, which contained the shorter form GlcNAc2(Hex)2-SQ-Hex-SQ. 24596091 9 90 theme H. 1594:1595 arg1 glycoprotein 1614:1625 the H. volcanii S-layer glycoprotein 1590:1625 the H. volcanii S-layer glycoprotein 1590:1625 This work describes a novel N-linked oligosaccharide containing a repeating SQ-Hex unit bound to Asn-732 of the H. volcanii S-layer glycoprotein, a position that had not been reported as glycosylated. 24596091 9 90 theme H. 1594:1595 arg1 position 1630:1637 a position 1628:1637 a position that had not been reported as glycosylated 1628:1680 This work describes a novel N-linked oligosaccharide containing a repeating SQ-Hex unit bound to Asn-732 of the H. volcanii S-layer glycoprotein, a position that had not been reported as glycosylated. 24596091 4 91 theme ABC 720:722 arg1 transporter 724:734 an ABC transporter 717:734 an ABC transporter component 717:744 Membrane preparations of MIG1 were enriched in two glycoproteins, identified as the S-layer glycoprotein and an ABC transporter component. 24596091 7 92 theme type 1125:1128 arg1 glycoprotein 1130:1141 the wild type glycoprotein 1116:1141 the wild type glycoprotein 1116:1141 Mass spectrometry analysis showed that the wild type glycoprotein released a novel oligosaccharide species corresponding to GlcNAc-GlcNAc(Hex)2-(SQ-Hex)6 in contrast to the mutant protein, which contained the shorter form GlcNAc2(Hex)2-SQ-Hex-SQ. 26291491 6 0 theme reduced 924:930 arg1 ability 932:938 a significantly reduced ability 908:938 a significantly reduced ability to infect GAKS cells 908:959 Moreover, sialidase inhibitor treated E. tarda showed a significantly reduced ability to infect GAKS cells. 26291491 9 1 link sialo-linked 1378:1389 arg1 glycoproteins 1391:1403 α2-3 sialo-linked glycoproteins 1373:1403 α2-3 sialo-linked glycoproteins 1373:1403 Supporting this finding, intact GAKS cell membrane exposed to recombinant NanA showed changes of glycoconjugates only in α2-3 sialo-linked glycoproteins, but not in glycolipids and α2-6 sialo-linked glycoproteins. 26291491 10 2 theme plausible 1604:1612 arg1 sialo-linkage 1547:1559 α2-3 sialo-linkage 1542:1559 α2-3 sialo-linkage of the N-linked glycoproteins 1542:1589 Lectin staining of cell surface glycoprotein provided further evidence that α2-3 sialo-linkage of the N-linked glycoproteins was the most plausible target of NanA sialidase. 26291491 10 2 theme plausible 1604:1612 arg1 target 1614:1619 the most plausible target 1595:1619 the most plausible target of NanA sialidase 1595:1637 Lectin staining of cell surface glycoprotein provided further evidence that α2-3 sialo-linkage of the N-linked glycoproteins was the most plausible target of NanA sialidase. 26291491 11 3 theme tarda 1711:1715 arg1 infection 1717:1725 E. tarda infection 1708:1725 E. tarda infection 1708:1725 To confirm the significance of α2-3 sialo-linkage desialylation for E. tarda infection, HeLa cells which possessed lower amount of α2-3 sialo-linkage glycoprotein were used for infection experiment along with GAKS cells. 26291491 13 4 theme mannose 2028:2034 arg1 pretreatment 2036:2047 mannose pretreatment 2028:2047 mannose pretreatment 2028:2047 Furthermore, E. tarda infection was significantly inhibited by mannose pretreatment suggesting that the bacterium potentially recognizes and binds to mannose or mannose containing chains following desialylation. 26291491 3 5 theme sialidase 499:507 arg1 aids 514:517 aids 514:517 aids 514:517 Recently, the relationship of NanA sialidase activity to E. tarda infection has been reported, however, the mechanism with which sialidase NanA aids the pathogenicity of E. tarda remained unclear. 26291491 1 6 theme fish 247:250 arg1 species 252:258 freshwater fish species 236:258 freshwater fish species 236:258 Edwardsiella tarda is one of the major pathogenic bacteria affecting both marine and freshwater fish species. 26291491 11 7 theme desialylation 1690:1702 arg1 significance 1655:1666 the significance 1651:1666 the significance of α2-3 sialo-linkage desialylation for E. tarda infection 1651:1725 To confirm the significance of α2-3 sialo-linkage desialylation for E. tarda infection, HeLa cells which possessed lower amount of α2-3 sialo-linkage glycoprotein were used for infection experiment along with GAKS cells. 26291491 8 8 theme α2-3 1197:1200 arg1 acid 1216:1219 α2-3 linked sialic acid 1197:1219 α2-3 linked sialic acid carrying sialoglycoconjugates 1197:1249 Among the natural substrates, NanA exhibited the highest activity towards 3-sialyllactose, α2-3 linked sialic acid carrying sialoglycoconjugates. 26291491 8 8 theme α2-3 1197:1200 arg1 3-sialyllactose 1180:1194 3-sialyllactose 1180:1194 3-sialyllactose 1180:1194 Among the natural substrates, NanA exhibited the highest activity towards 3-sialyllactose, α2-3 linked sialic acid carrying sialoglycoconjugates. 26291491 10 9 theme sialidase 1629:1637 arg1 sialo-linkage 1547:1559 α2-3 sialo-linkage 1542:1559 α2-3 sialo-linkage of the N-linked glycoproteins 1542:1589 Lectin staining of cell surface glycoprotein provided further evidence that α2-3 sialo-linkage of the N-linked glycoproteins was the most plausible target of NanA sialidase. 26291491 10 9 theme sialidase 1629:1637 arg1 target 1614:1619 the most plausible target 1595:1619 the most plausible target of NanA sialidase 1595:1637 Lectin staining of cell surface glycoprotein provided further evidence that α2-3 sialo-linkage of the N-linked glycoproteins was the most plausible target of NanA sialidase. 26291491 2 10 theme Sialidase 261:269 arg1 NanA 271:274 Sialidase NanA 261:274 Sialidase NanA expressed endogenously in E. tarda 261:309 Sialidase NanA expressed endogenously in E. tarda is glycosidase removing sialic acids from glycoconjugates. 26291491 8 11 theme sialic 1209:1214 arg1 acid 1216:1219 α2-3 linked sialic acid 1197:1219 α2-3 linked sialic acid carrying sialoglycoconjugates 1197:1249 Among the natural substrates, NanA exhibited the highest activity towards 3-sialyllactose, α2-3 linked sialic acid carrying sialoglycoconjugates. 26291491 8 11 theme sialic 1209:1214 arg1 3-sialyllactose 1180:1194 3-sialyllactose 1180:1194 3-sialyllactose 1180:1194 Among the natural substrates, NanA exhibited the highest activity towards 3-sialyllactose, α2-3 linked sialic acid carrying sialoglycoconjugates. 26291491 6 12 theme treated 884:890 arg1 tarda 895:899 sialidase inhibitor treated E. tarda 864:899 sialidase inhibitor treated E. tarda 864:899 Moreover, sialidase inhibitor treated E. tarda showed a significantly reduced ability to infect GAKS cells. 26291491 0 13 theme tarda 134:138 arg1 infection 140:148 Edwardsiella tarda infection 121:148 Edwardsiella tarda infection 121:148 Recombinant sialidase NanA (rNanA) cleaves α2-3 linked sialic acid of host cell surface N-linked glycoprotein to promote Edwardsiella tarda infection. 26291491 10 14 theme Lectin 1466:1471 arg1 staining 1473:1480 Lectin staining 1466:1480 Lectin staining of cell surface glycoprotein 1466:1509 Lectin staining of cell surface glycoprotein provided further evidence that α2-3 sialo-linkage of the N-linked glycoproteins was the most plausible target of NanA sialidase. 26291491 5 15 theme increased 806:814 arg1 susceptibility 816:829 increased susceptibility 806:829 increased susceptibility to E. tarda infection 806:851 GAKS cell pretreated with recombinant NanA showed increased susceptibility to E. tarda infection. 26291491 4 16 theme NanA 633:636 arg1 properties 619:628 the biochemical properties 603:628 the biochemical properties of NanA towards various substrates 603:663 Here, we comprehensively determined the biochemical properties of NanA towards various substrates in vitro to provide novel insights on the potential NanA target molecule at the host cell. 26291491 14 17 theme desialylate 2253:2263 arg1 glycoproteins 2270:2282 desialylate α2-3 glycoproteins 2253:2282 desialylate α2-3 glycoproteins 2253:2282 Together, these results suggest that E. tarda may employ endogenous NanA to desialylate α2-3 glycoproteins on host cells, thus revealing one of the potential binding molecules during infection. 26291491 7 18 theme tarda 1089:1093 arg1 infection 1095:1103 E. tarda infection 1086:1103 E. tarda infection 1086:1103 These results indicate that NanA-induced desialylation of cell surface glycoconjugates is essential for the initial step of E. tarda infection. 26291491 5 19 theme tarda 837:841 arg1 infection 843:851 E. tarda infection 834:851 E. tarda infection 834:851 GAKS cell pretreated with recombinant NanA showed increased susceptibility to E. tarda infection. 26291491 4 20 theme various 646:652 arg1 substrates 654:663 various substrates 646:663 various substrates 646:663 Here, we comprehensively determined the biochemical properties of NanA towards various substrates in vitro to provide novel insights on the potential NanA target molecule at the host cell. 26291491 9 21 theme intact 1277:1282 arg1 membrane 1294:1301 intact GAKS cell membrane 1277:1301 intact GAKS cell membrane exposed to recombinant NanA 1277:1329 Supporting this finding, intact GAKS cell membrane exposed to recombinant NanA showed changes of glycoconjugates only in α2-3 sialo-linked glycoproteins, but not in glycolipids and α2-6 sialo-linked glycoproteins. 26291491 7 22 theme glycoconjugates 1033:1047 arg1 desialylation 1003:1015 NanA-induced desialylation 990:1015 NanA-induced desialylation of cell surface glycoconjugates 990:1047 These results indicate that NanA-induced desialylation of cell surface glycoconjugates is essential for the initial step of E. tarda infection. 26291491 1 23 theme bacteria 201:208 arg1 one 173:175 one 173:175 one 173:175 Edwardsiella tarda is one of the major pathogenic bacteria affecting both marine and freshwater fish species. 26291491 1 23 theme bacteria 201:208 arg1 bacteria 201:208 the major pathogenic bacteria 180:208 the major pathogenic bacteria affecting both marine and freshwater fish species 180:258 Edwardsiella tarda is one of the major pathogenic bacteria affecting both marine and freshwater fish species. 26291491 6 24 theme GAKS 950:953 arg1 cells 955:959 GAKS cells 950:959 GAKS cells 950:959 Moreover, sialidase inhibitor treated E. tarda showed a significantly reduced ability to infect GAKS cells. 26291491 4 25 theme potential 707:715 arg1 molecule 729:736 the potential NanA target molecule 703:736 the potential NanA target molecule at the host cell 703:753 Here, we comprehensively determined the biochemical properties of NanA towards various substrates in vitro to provide novel insights on the potential NanA target molecule at the host cell. 26291491 7 26 theme initial 1070:1076 arg1 step 1078:1081 the initial step 1066:1081 the initial step of E. tarda infection 1066:1103 These results indicate that NanA-induced desialylation of cell surface glycoconjugates is essential for the initial step of E. tarda infection. 26291491 9 27 theme cell 1289:1292 arg1 membrane 1294:1301 intact GAKS cell membrane 1277:1301 intact GAKS cell membrane exposed to recombinant NanA 1277:1329 Supporting this finding, intact GAKS cell membrane exposed to recombinant NanA showed changes of glycoconjugates only in α2-3 sialo-linked glycoproteins, but not in glycolipids and α2-6 sialo-linked glycoproteins. 26291491 7 28 theme cell 1020:1023 arg1 glycoconjugates 1033:1047 cell surface glycoconjugates 1020:1047 cell surface glycoconjugates 1020:1047 These results indicate that NanA-induced desialylation of cell surface glycoconjugates is essential for the initial step of E. tarda infection. 26291491 14 29 from NanA 2245:2248 arg1 cells 2292:2296 host cells 2287:2296 host cells 2287:2296 Together, these results suggest that E. tarda may employ endogenous NanA to desialylate α2-3 glycoproteins on host cells, thus revealing one of the potential binding molecules during infection. 26291491 4 30 theme target 722:727 arg1 molecule 729:736 the potential NanA target molecule 703:736 the potential NanA target molecule at the host cell 703:753 Here, we comprehensively determined the biochemical properties of NanA towards various substrates in vitro to provide novel insights on the potential NanA target molecule at the host cell. 26291491 13 31 theme E. 1978:1979 arg1 infection 1987:1995 E. tarda infection 1978:1995 E. tarda infection 1978:1995 Furthermore, E. tarda infection was significantly inhibited by mannose pretreatment suggesting that the bacterium potentially recognizes and binds to mannose or mannose containing chains following desialylation. 26291491 8 32 contain carrying 1221:1228 arg1 acid 1216:1219 α2-3 linked sialic acid 1197:1219 α2-3 linked sialic acid carrying sialoglycoconjugates 1197:1249 Among the natural substrates, NanA exhibited the highest activity towards 3-sialyllactose, α2-3 linked sialic acid carrying sialoglycoconjugates. 26291491 8 32 contain carrying 1221:1228 arg1 3-sialyllactose 1180:1194 3-sialyllactose 1180:1194 3-sialyllactose 1180:1194 Among the natural substrates, NanA exhibited the highest activity towards 3-sialyllactose, α2-3 linked sialic acid carrying sialoglycoconjugates. 26291491 8 32 contain carrying 1221:1228 arg2 sialoglycoconjugates 1230:1249 sialoglycoconjugates 1230:1249 sialoglycoconjugates 1230:1249 Among the natural substrates, NanA exhibited the highest activity towards 3-sialyllactose, α2-3 linked sialic acid carrying sialoglycoconjugates. 26291491 4 33 theme novel 685:689 arg1 insights 691:698 novel insights 685:698 novel insights on the potential NanA target molecule at the host cell 685:753 Here, we comprehensively determined the biochemical properties of NanA towards various substrates in vitro to provide novel insights on the potential NanA target molecule at the host cell. 26291491 11 34 theme infection 1817:1825 arg1 experiment 1827:1836 infection experiment 1817:1836 infection experiment 1817:1836 To confirm the significance of α2-3 sialo-linkage desialylation for E. tarda infection, HeLa cells which possessed lower amount of α2-3 sialo-linkage glycoprotein were used for infection experiment along with GAKS cells. 26291491 0 35 theme linked 48:53 arg1 acid 62:65 α2-3 linked sialic acid 43:65 α2-3 linked sialic acid of host cell surface N-linked glycoprotein 43:108 Recombinant sialidase NanA (rNanA) cleaves α2-3 linked sialic acid of host cell surface N-linked glycoprotein to promote Edwardsiella tarda infection. 26291491 9 36 theme recombinant 1314:1324 arg1 NanA 1326:1329 recombinant NanA 1314:1329 recombinant NanA 1314:1329 Supporting this finding, intact GAKS cell membrane exposed to recombinant NanA showed changes of glycoconjugates only in α2-3 sialo-linked glycoproteins, but not in glycolipids and α2-6 sialo-linked glycoproteins. 26291491 1 37 theme Edwardsiella 151:162 arg1 tarda 164:168 Edwardsiella tarda 151:168 Edwardsiella tarda 151:168 Edwardsiella tarda is one of the major pathogenic bacteria affecting both marine and freshwater fish species. 26291491 10 38 theme surface 1490:1496 arg1 glycoprotein 1498:1509 cell surface glycoprotein 1485:1509 cell surface glycoprotein 1485:1509 Lectin staining of cell surface glycoprotein provided further evidence that α2-3 sialo-linkage of the N-linked glycoproteins was the most plausible target of NanA sialidase. 26291491 11 39 theme GAKS 1849:1852 arg1 cells 1854:1858 GAKS cells 1849:1858 GAKS cells 1849:1858 To confirm the significance of α2-3 sialo-linkage desialylation for E. tarda infection, HeLa cells which possessed lower amount of α2-3 sialo-linkage glycoprotein were used for infection experiment along with GAKS cells. 26291491 0 40 theme host 70:73 arg1 cell 75:78 host cell surface N-linked glycoprotein 70:108 host cell surface N-linked glycoprotein 70:108 Recombinant sialidase NanA (rNanA) cleaves α2-3 linked sialic acid of host cell surface N-linked glycoprotein to promote Edwardsiella tarda infection. 26291491 11 41 gly glycoprotein 1790:1801 arg1 glycoprotein 1790:1801 α2-3 sialo-linkage glycoprotein 1771:1801 α2-3 sialo-linkage glycoprotein 1771:1801 To confirm the significance of α2-3 sialo-linkage desialylation for E. tarda infection, HeLa cells which possessed lower amount of α2-3 sialo-linkage glycoprotein were used for infection experiment along with GAKS cells. 26291491 10 42 theme α2-3 1542:1545 arg1 sialo-linkage 1547:1559 α2-3 sialo-linkage 1542:1559 α2-3 sialo-linkage of the N-linked glycoproteins 1542:1589 Lectin staining of cell surface glycoprotein provided further evidence that α2-3 sialo-linkage of the N-linked glycoproteins was the most plausible target of NanA sialidase. 26291491 10 42 theme α2-3 1542:1545 arg1 target 1614:1619 the most plausible target 1595:1619 the most plausible target of NanA sialidase 1595:1637 Lectin staining of cell surface glycoprotein provided further evidence that α2-3 sialo-linkage of the N-linked glycoproteins was the most plausible target of NanA sialidase. 26291491 0 43 theme surface 80:86 arg1 glycoprotein 97:108 surface N-linked glycoprotein 80:108 host cell surface N-linked glycoprotein 70:108 Recombinant sialidase NanA (rNanA) cleaves α2-3 linked sialic acid of host cell surface N-linked glycoprotein to promote Edwardsiella tarda infection. 26291491 13 44 theme containing 2134:2143 arg1 chains 2145:2150 mannose containing chains 2126:2150 mannose containing chains 2126:2150 Furthermore, E. tarda infection was significantly inhibited by mannose pretreatment suggesting that the bacterium potentially recognizes and binds to mannose or mannose containing chains following desialylation. 26291491 12 45 theme GAKS 1953:1956 arg1 cells 1958:1962 GAKS cells 1953:1962 GAKS cells 1953:1962 As a result, infection of HeLa cells by E. tarda was significantly reduced when compared to GAKS cells. 26291491 3 46 theme E. 427:428 arg1 infection 436:444 E. tarda infection 427:444 E. tarda infection 427:444 Recently, the relationship of NanA sialidase activity to E. tarda infection has been reported, however, the mechanism with which sialidase NanA aids the pathogenicity of E. tarda remained unclear. 26291491 0 47 theme Recombinant 0:10 arg1 NanA 22:25 Recombinant sialidase NanA 0:25 Recombinant sialidase NanA (rNanA) 0:33 Recombinant sialidase NanA (rNanA) cleaves α2-3 linked sialic acid of host cell surface N-linked glycoprotein to promote Edwardsiella tarda infection. 26291491 0 47 theme Recombinant 0:10 arg1 rNanA 28:32 rNanA 28:32 rNanA 28:32 Recombinant sialidase NanA (rNanA) cleaves α2-3 linked sialic acid of host cell surface N-linked glycoprotein to promote Edwardsiella tarda infection. 26291491 7 48 gly desialylation 1003:1015 arg1 infection 1095:1103 E. tarda infection 1086:1103 E. tarda infection 1086:1103 These results indicate that NanA-induced desialylation of cell surface glycoconjugates is essential for the initial step of E. tarda infection. 26291491 7 48 gly desialylation 1003:1015 arg1 glycoconjugates 1033:1047 cell surface glycoconjugates 1020:1047 cell surface glycoconjugates 1020:1047 These results indicate that NanA-induced desialylation of cell surface glycoconjugates is essential for the initial step of E. tarda infection. 26291491 10 49 theme N-linked 1568:1575 arg1 glycoproteins 1577:1589 the N-linked glycoproteins 1564:1589 the N-linked glycoproteins 1564:1589 Lectin staining of cell surface glycoprotein provided further evidence that α2-3 sialo-linkage of the N-linked glycoproteins was the most plausible target of NanA sialidase. 26291491 4 50 theme host 745:748 arg1 cell 750:753 the host cell 741:753 the host cell 741:753 Here, we comprehensively determined the biochemical properties of NanA towards various substrates in vitro to provide novel insights on the potential NanA target molecule at the host cell. 26291491 14 51 theme molecules 2343:2351 arg1 molecules 2343:2351 the potential binding molecules 2321:2351 the potential binding molecules during infection 2321:2368 Together, these results suggest that E. tarda may employ endogenous NanA to desialylate α2-3 glycoproteins on host cells, thus revealing one of the potential binding molecules during infection. 26291491 14 51 theme molecules 2343:2351 arg1 one 2314:2316 one 2314:2316 one 2314:2316 Together, these results suggest that E. tarda may employ endogenous NanA to desialylate α2-3 glycoproteins on host cells, thus revealing one of the potential binding molecules during infection. 26291491 6 52 theme inhibitor 874:882 arg1 tarda 895:899 sialidase inhibitor treated E. tarda 864:899 sialidase inhibitor treated E. tarda 864:899 Moreover, sialidase inhibitor treated E. tarda showed a significantly reduced ability to infect GAKS cells. 26291491 0 53 dep linked 48:53 arg1 α2-3 43:46 α2-3 43:46 α2-3 43:46 Recombinant sialidase NanA (rNanA) cleaves α2-3 linked sialic acid of host cell surface N-linked glycoprotein to promote Edwardsiella tarda infection. 26291491 3 54 theme activity 415:422 arg1 relationship 384:395 the relationship 380:395 the relationship of NanA sialidase activity to E. tarda infection 380:444 Recently, the relationship of NanA sialidase activity to E. tarda infection has been reported, however, the mechanism with which sialidase NanA aids the pathogenicity of E. tarda remained unclear. 26291491 11 55 theme sialo-linkage 1776:1788 arg1 glycoprotein 1790:1801 α2-3 sialo-linkage glycoprotein 1771:1801 α2-3 sialo-linkage glycoprotein 1771:1801 To confirm the significance of α2-3 sialo-linkage desialylation for E. tarda infection, HeLa cells which possessed lower amount of α2-3 sialo-linkage glycoprotein were used for infection experiment along with GAKS cells. 26291491 14 56 theme potential 2325:2333 arg1 molecules 2343:2351 the potential binding molecules 2321:2351 the potential binding molecules during infection 2321:2368 Together, these results suggest that E. tarda may employ endogenous NanA to desialylate α2-3 glycoproteins on host cells, thus revealing one of the potential binding molecules during infection. 26291491 12 57 theme HeLa 1887:1890 arg1 cells 1892:1896 HeLa cells 1887:1896 HeLa cells 1887:1896 As a result, infection of HeLa cells by E. tarda was significantly reduced when compared to GAKS cells. 26291491 14 58 theme host 2287:2290 arg1 cells 2292:2296 host cells 2287:2296 host cells 2287:2296 Together, these results suggest that E. tarda may employ endogenous NanA to desialylate α2-3 glycoproteins on host cells, thus revealing one of the potential binding molecules during infection. 26291491 3 59 theme NanA 400:403 arg1 activity 415:422 NanA sialidase activity 400:422 NanA sialidase activity 400:422 Recently, the relationship of NanA sialidase activity to E. tarda infection has been reported, however, the mechanism with which sialidase NanA aids the pathogenicity of E. tarda remained unclear. 26291491 9 60 gly glycoproteins 1451:1463 arg1 glycoproteins 1451:1463 α2-6 sialo-linked glycoproteins 1433:1463 α2-6 sialo-linked glycoproteins 1433:1463 Supporting this finding, intact GAKS cell membrane exposed to recombinant NanA showed changes of glycoconjugates only in α2-3 sialo-linked glycoproteins, but not in glycolipids and α2-6 sialo-linked glycoproteins. 26291491 11 61 theme α2-3 1671:1674 arg1 desialylation 1690:1702 α2-3 sialo-linkage desialylation 1671:1702 α2-3 sialo-linkage desialylation 1671:1702 To confirm the significance of α2-3 sialo-linkage desialylation for E. tarda infection, HeLa cells which possessed lower amount of α2-3 sialo-linkage glycoprotein were used for infection experiment along with GAKS cells. 26291491 8 62 theme natural 1116:1122 arg1 substrates 1124:1133 the natural substrates 1112:1133 the natural substrates 1112:1133 Among the natural substrates, NanA exhibited the highest activity towards 3-sialyllactose, α2-3 linked sialic acid carrying sialoglycoconjugates. 26291491 0 63 link N-linked 88:95 arg1 glycoprotein 97:108 surface N-linked glycoprotein 80:108 host cell surface N-linked glycoprotein 70:108 Recombinant sialidase NanA (rNanA) cleaves α2-3 linked sialic acid of host cell surface N-linked glycoprotein to promote Edwardsiella tarda infection. 26291491 10 64 theme NanA 1624:1627 arg1 sialidase 1629:1637 NanA sialidase 1624:1637 NanA sialidase 1624:1637 Lectin staining of cell surface glycoprotein provided further evidence that α2-3 sialo-linkage of the N-linked glycoproteins was the most plausible target of NanA sialidase. 26291491 11 65 theme E. 1708:1709 arg1 infection 1717:1725 E. tarda infection 1708:1725 E. tarda infection 1708:1725 To confirm the significance of α2-3 sialo-linkage desialylation for E. tarda infection, HeLa cells which possessed lower amount of α2-3 sialo-linkage glycoprotein were used for infection experiment along with GAKS cells. 26291491 3 66 theme NanA 509:512 arg1 aids 514:517 aids 514:517 aids 514:517 Recently, the relationship of NanA sialidase activity to E. tarda infection has been reported, however, the mechanism with which sialidase NanA aids the pathogenicity of E. tarda remained unclear. 26291491 9 67 theme sialo-linked 1438:1449 arg1 glycoproteins 1451:1463 α2-6 sialo-linked glycoproteins 1433:1463 α2-6 sialo-linked glycoproteins 1433:1463 Supporting this finding, intact GAKS cell membrane exposed to recombinant NanA showed changes of glycoconjugates only in α2-3 sialo-linked glycoproteins, but not in glycolipids and α2-6 sialo-linked glycoproteins. 26291491 10 68 gly glycoprotein 1498:1509 arg1 glycoprotein 1498:1509 cell surface glycoprotein 1485:1509 cell surface glycoprotein 1485:1509 Lectin staining of cell surface glycoprotein provided further evidence that α2-3 sialo-linkage of the N-linked glycoproteins was the most plausible target of NanA sialidase. 26291491 4 69 theme biochemical 607:617 arg1 properties 619:628 the biochemical properties 603:628 the biochemical properties of NanA towards various substrates 603:663 Here, we comprehensively determined the biochemical properties of NanA towards various substrates in vitro to provide novel insights on the potential NanA target molecule at the host cell. 26291491 11 70 theme HeLa 1728:1731 arg1 cells 1733:1737 HeLa cells 1728:1737 HeLa cells which possessed lower amount of α2-3 sialo-linkage glycoprotein 1728:1801 To confirm the significance of α2-3 sialo-linkage desialylation for E. tarda infection, HeLa cells which possessed lower amount of α2-3 sialo-linkage glycoprotein were used for infection experiment along with GAKS cells. 26291491 2 71 attach removing 326:333 arg2 glycosidase 314:324 glycosidase 314:324 glycosidase removing sialic acids from glycoconjugates 314:367 Sialidase NanA expressed endogenously in E. tarda is glycosidase removing sialic acids from glycoconjugates. 26291491 2 71 attach removing 326:333 arg1 glycoconjugates 353:367 glycoconjugates 353:367 glycoconjugates 353:367 Sialidase NanA expressed endogenously in E. tarda is glycosidase removing sialic acids from glycoconjugates. 26291491 4 72 from insights 691:698 arg1 molecule 729:736 the potential NanA target molecule 703:736 the potential NanA target molecule at the host cell 703:753 Here, we comprehensively determined the biochemical properties of NanA towards various substrates in vitro to provide novel insights on the potential NanA target molecule at the host cell. 26291491 1 73 theme freshwater 236:245 arg1 species 252:258 freshwater fish species 236:258 freshwater fish species 236:258 Edwardsiella tarda is one of the major pathogenic bacteria affecting both marine and freshwater fish species. 26291491 8 74 theme highest 1155:1161 arg1 activity 1163:1170 the highest activity 1151:1170 the highest activity towards 3-sialyllactose, α2-3 linked sialic acid carrying sialoglycoconjugates 1151:1249 Among the natural substrates, NanA exhibited the highest activity towards 3-sialyllactose, α2-3 linked sialic acid carrying sialoglycoconjugates. 26291491 1 75 theme major 184:188 arg1 bacteria 201:208 the major pathogenic bacteria 180:208 the major pathogenic bacteria affecting both marine and freshwater fish species 180:258 Edwardsiella tarda is one of the major pathogenic bacteria affecting both marine and freshwater fish species. 26291491 11 76 theme lower 1755:1759 arg1 amount 1761:1766 lower amount 1755:1766 lower amount of α2-3 sialo-linkage glycoprotein 1755:1801 To confirm the significance of α2-3 sialo-linkage desialylation for E. tarda infection, HeLa cells which possessed lower amount of α2-3 sialo-linkage glycoprotein were used for infection experiment along with GAKS cells. 26291491 11 76 theme lower 1755:1759 arg1 glycoprotein 1790:1801 α2-3 sialo-linkage glycoprotein 1771:1801 α2-3 sialo-linkage glycoprotein 1771:1801 To confirm the significance of α2-3 sialo-linkage desialylation for E. tarda infection, HeLa cells which possessed lower amount of α2-3 sialo-linkage glycoprotein were used for infection experiment along with GAKS cells. 26291491 11 77 used used 1808:1811 arg2 cells 1733:1737 HeLa cells 1728:1737 HeLa cells which possessed lower amount of α2-3 sialo-linkage glycoprotein 1728:1801 To confirm the significance of α2-3 sialo-linkage desialylation for E. tarda infection, HeLa cells which possessed lower amount of α2-3 sialo-linkage glycoprotein were used for infection experiment along with GAKS cells. 26291491 6 78 theme E. 892:893 arg1 tarda 895:899 sialidase inhibitor treated E. tarda 864:899 sialidase inhibitor treated E. tarda 864:899 Moreover, sialidase inhibitor treated E. tarda showed a significantly reduced ability to infect GAKS cells. 26291491 9 79 link sialo-linked 1438:1449 arg1 glycoproteins 1451:1463 α2-6 sialo-linked glycoproteins 1433:1463 α2-6 sialo-linked glycoproteins 1433:1463 Supporting this finding, intact GAKS cell membrane exposed to recombinant NanA showed changes of glycoconjugates only in α2-3 sialo-linked glycoproteins, but not in glycolipids and α2-6 sialo-linked glycoproteins. 26291491 10 80 gly glycoproteins 1577:1589 arg1 glycoproteins 1577:1589 the N-linked glycoproteins 1564:1589 the N-linked glycoproteins 1564:1589 Lectin staining of cell surface glycoprotein provided further evidence that α2-3 sialo-linkage of the N-linked glycoproteins was the most plausible target of NanA sialidase. 26291491 7 81 theme infection 1095:1103 arg1 step 1078:1081 the initial step 1066:1081 the initial step of E. tarda infection 1066:1103 These results indicate that NanA-induced desialylation of cell surface glycoconjugates is essential for the initial step of E. tarda infection. 26291491 8 82 theme linked 1202:1207 arg1 acid 1216:1219 α2-3 linked sialic acid 1197:1219 α2-3 linked sialic acid carrying sialoglycoconjugates 1197:1249 Among the natural substrates, NanA exhibited the highest activity towards 3-sialyllactose, α2-3 linked sialic acid carrying sialoglycoconjugates. 26291491 8 82 theme linked 1202:1207 arg1 3-sialyllactose 1180:1194 3-sialyllactose 1180:1194 3-sialyllactose 1180:1194 Among the natural substrates, NanA exhibited the highest activity towards 3-sialyllactose, α2-3 linked sialic acid carrying sialoglycoconjugates. 26291491 14 83 theme α2-3 2265:2268 arg1 glycoproteins 2270:2282 desialylate α2-3 glycoproteins 2253:2282 desialylate α2-3 glycoproteins 2253:2282 Together, these results suggest that E. tarda may employ endogenous NanA to desialylate α2-3 glycoproteins on host cells, thus revealing one of the potential binding molecules during infection. 26291491 7 84 theme E. 1086:1087 arg1 infection 1095:1103 E. tarda infection 1086:1103 E. tarda infection 1086:1103 These results indicate that NanA-induced desialylation of cell surface glycoconjugates is essential for the initial step of E. tarda infection. 26291491 3 85 theme tarda 543:547 arg1 pathogenicity 523:535 the pathogenicity 519:535 the pathogenicity of E. tarda 519:547 Recently, the relationship of NanA sialidase activity to E. tarda infection has been reported, however, the mechanism with which sialidase NanA aids the pathogenicity of E. tarda remained unclear. 26291491 5 86 theme E. 834:835 arg1 infection 843:851 E. tarda infection 834:851 E. tarda infection 834:851 GAKS cell pretreated with recombinant NanA showed increased susceptibility to E. tarda infection. 26291491 0 87 theme Edwardsiella 121:132 arg1 tarda 134:138 Edwardsiella tarda 121:138 Edwardsiella tarda infection 121:148 Recombinant sialidase NanA (rNanA) cleaves α2-3 linked sialic acid of host cell surface N-linked glycoprotein to promote Edwardsiella tarda infection. 26291491 1 88 theme pathogenic 190:199 arg1 bacteria 201:208 the major pathogenic bacteria 180:208 the major pathogenic bacteria affecting both marine and freshwater fish species 180:258 Edwardsiella tarda is one of the major pathogenic bacteria affecting both marine and freshwater fish species. 26291491 9 89 from changes 1338:1344 arg1 glycoproteins 1391:1403 α2-3 sialo-linked glycoproteins 1373:1403 α2-3 sialo-linked glycoproteins 1373:1403 Supporting this finding, intact GAKS cell membrane exposed to recombinant NanA showed changes of glycoconjugates only in α2-3 sialo-linked glycoproteins, but not in glycolipids and α2-6 sialo-linked glycoproteins. 26291491 9 89 from changes 1338:1344 arg1 glycoproteins 1451:1463 α2-6 sialo-linked glycoproteins 1433:1463 α2-6 sialo-linked glycoproteins 1433:1463 Supporting this finding, intact GAKS cell membrane exposed to recombinant NanA showed changes of glycoconjugates only in α2-3 sialo-linked glycoproteins, but not in glycolipids and α2-6 sialo-linked glycoproteins. 26291491 9 89 from changes 1338:1344 arg1 glycolipids 1417:1427 glycolipids 1417:1427 glycolipids 1417:1427 Supporting this finding, intact GAKS cell membrane exposed to recombinant NanA showed changes of glycoconjugates only in α2-3 sialo-linked glycoproteins, but not in glycolipids and α2-6 sialo-linked glycoproteins. 26291491 14 90 theme endogenous 2234:2243 arg1 NanA 2245:2248 endogenous NanA 2234:2248 endogenous NanA to desialylate α2-3 glycoproteins on host cells 2234:2296 Together, these results suggest that E. tarda may employ endogenous NanA to desialylate α2-3 glycoproteins on host cells, thus revealing one of the potential binding molecules during infection. 26291491 9 91 theme GAKS 1284:1287 arg1 membrane 1294:1301 intact GAKS cell membrane 1277:1301 intact GAKS cell membrane exposed to recombinant NanA 1277:1329 Supporting this finding, intact GAKS cell membrane exposed to recombinant NanA showed changes of glycoconjugates only in α2-3 sialo-linked glycoproteins, but not in glycolipids and α2-6 sialo-linked glycoproteins. 26291491 0 92 gly glycoprotein 97:108 arg1 glycoprotein 97:108 surface N-linked glycoprotein 80:108 host cell surface N-linked glycoprotein 70:108 Recombinant sialidase NanA (rNanA) cleaves α2-3 linked sialic acid of host cell surface N-linked glycoprotein to promote Edwardsiella tarda infection. 26291491 14 93 theme E. 2214:2215 arg1 tarda 2217:2221 E. tarda 2214:2221 E. tarda 2214:2221 Together, these results suggest that E. tarda may employ endogenous NanA to desialylate α2-3 glycoproteins on host cells, thus revealing one of the potential binding molecules during infection. 26291491 7 94 theme surface 1025:1031 arg1 glycoconjugates 1033:1047 cell surface glycoconjugates 1020:1047 cell surface glycoconjugates 1020:1047 These results indicate that NanA-induced desialylation of cell surface glycoconjugates is essential for the initial step of E. tarda infection. 26291491 12 95 theme cells 1892:1896 arg1 infection 1874:1882 infection 1874:1882 infection of HeLa cells by E. tarda 1874:1908 As a result, infection of HeLa cells by E. tarda was significantly reduced when compared to GAKS cells. 26291491 12 95 theme cells 1892:1896 arg1 result 1866:1871 a result 1864:1871 a result 1864:1871 As a result, infection of HeLa cells by E. tarda was significantly reduced when compared to GAKS cells. 26291491 4 96 theme NanA 717:720 arg1 molecule 729:736 the potential NanA target molecule 703:736 the potential NanA target molecule at the host cell 703:753 Here, we comprehensively determined the biochemical properties of NanA towards various substrates in vitro to provide novel insights on the potential NanA target molecule at the host cell. 26291491 13 97 theme tarda 1981:1985 arg1 infection 1987:1995 E. tarda infection 1978:1995 E. tarda infection 1978:1995 Furthermore, E. tarda infection was significantly inhibited by mannose pretreatment suggesting that the bacterium potentially recognizes and binds to mannose or mannose containing chains following desialylation. 26291491 0 98 theme sialic 55:60 arg1 acid 62:65 α2-3 linked sialic acid 43:65 α2-3 linked sialic acid of host cell surface N-linked glycoprotein 43:108 Recombinant sialidase NanA (rNanA) cleaves α2-3 linked sialic acid of host cell surface N-linked glycoprotein to promote Edwardsiella tarda infection. 26291491 5 99 theme GAKS 756:759 arg1 cell 761:764 GAKS cell 756:764 GAKS cell pretreated with recombinant NanA 756:797 GAKS cell pretreated with recombinant NanA showed increased susceptibility to E. tarda infection. 26291491 7 100 theme NanA-induced 990:1001 arg1 desialylation 1003:1015 NanA-induced desialylation 990:1015 NanA-induced desialylation of cell surface glycoconjugates 990:1047 These results indicate that NanA-induced desialylation of cell surface glycoconjugates is essential for the initial step of E. tarda infection. 26291491 10 101 theme glycoprotein 1498:1509 arg1 staining 1473:1480 Lectin staining 1466:1480 Lectin staining of cell surface glycoprotein 1466:1509 Lectin staining of cell surface glycoprotein provided further evidence that α2-3 sialo-linkage of the N-linked glycoproteins was the most plausible target of NanA sialidase. 26291491 0 102 theme cell 75:78 arg1 acid 62:65 α2-3 linked sialic acid 43:65 α2-3 linked sialic acid of host cell surface N-linked glycoprotein 43:108 Recombinant sialidase NanA (rNanA) cleaves α2-3 linked sialic acid of host cell surface N-linked glycoprotein to promote Edwardsiella tarda infection. 26291491 10 103 theme cell 1485:1488 arg1 glycoprotein 1498:1509 cell surface glycoprotein 1485:1509 cell surface glycoprotein 1485:1509 Lectin staining of cell surface glycoprotein provided further evidence that α2-3 sialo-linkage of the N-linked glycoproteins was the most plausible target of NanA sialidase. 26291491 0 104 theme N-linked 88:95 arg1 glycoprotein 97:108 surface N-linked glycoprotein 80:108 host cell surface N-linked glycoprotein 70:108 Recombinant sialidase NanA (rNanA) cleaves α2-3 linked sialic acid of host cell surface N-linked glycoprotein to promote Edwardsiella tarda infection. 26291491 9 105 theme glycoconjugates 1349:1363 arg1 changes 1338:1344 changes 1338:1344 changes of glycoconjugates only in α2-3 sialo-linked glycoproteins, but not in glycolipids and α2-6 sialo-linked glycoproteins 1338:1463 Supporting this finding, intact GAKS cell membrane exposed to recombinant NanA showed changes of glycoconjugates only in α2-3 sialo-linked glycoproteins, but not in glycolipids and α2-6 sialo-linked glycoproteins. 26291491 4 106 from cell 750:753 arg1 molecule 729:736 the potential NanA target molecule 703:736 the potential NanA target molecule at the host cell 703:753 Here, we comprehensively determined the biochemical properties of NanA towards various substrates in vitro to provide novel insights on the potential NanA target molecule at the host cell. 26291491 0 107 dep cell 75:78 arg1 glycoprotein 97:108 surface N-linked glycoprotein 80:108 host cell surface N-linked glycoprotein 70:108 Recombinant sialidase NanA (rNanA) cleaves α2-3 linked sialic acid of host cell surface N-linked glycoprotein to promote Edwardsiella tarda infection. 26291491 9 108 gly glycoproteins 1391:1403 arg1 glycoproteins 1391:1403 α2-3 sialo-linked glycoproteins 1373:1403 α2-3 sialo-linked glycoproteins 1373:1403 Supporting this finding, intact GAKS cell membrane exposed to recombinant NanA showed changes of glycoconjugates only in α2-3 sialo-linked glycoproteins, but not in glycolipids and α2-6 sialo-linked glycoproteins. 26291491 10 109 link N-linked 1568:1575 arg1 glycoproteins 1577:1589 the N-linked glycoproteins 1564:1589 the N-linked glycoproteins 1564:1589 Lectin staining of cell surface glycoprotein provided further evidence that α2-3 sialo-linkage of the N-linked glycoproteins was the most plausible target of NanA sialidase. 26291491 0 110 theme sialidase 12:20 arg1 NanA 22:25 Recombinant sialidase NanA 0:25 Recombinant sialidase NanA (rNanA) 0:33 Recombinant sialidase NanA (rNanA) cleaves α2-3 linked sialic acid of host cell surface N-linked glycoprotein to promote Edwardsiella tarda infection. 26291491 0 110 theme sialidase 12:20 arg1 rNanA 28:32 rNanA 28:32 rNanA 28:32 Recombinant sialidase NanA (rNanA) cleaves α2-3 linked sialic acid of host cell surface N-linked glycoprotein to promote Edwardsiella tarda infection. 26291491 11 111 contain possessed 1745:1753 arg2 amount 1761:1766 lower amount 1755:1766 lower amount of α2-3 sialo-linkage glycoprotein 1755:1801 To confirm the significance of α2-3 sialo-linkage desialylation for E. tarda infection, HeLa cells which possessed lower amount of α2-3 sialo-linkage glycoprotein were used for infection experiment along with GAKS cells. 26291491 11 111 contain possessed 1745:1753 arg2 glycoprotein 1790:1801 α2-3 sialo-linkage glycoprotein 1771:1801 α2-3 sialo-linkage glycoprotein 1771:1801 To confirm the significance of α2-3 sialo-linkage desialylation for E. tarda infection, HeLa cells which possessed lower amount of α2-3 sialo-linkage glycoprotein were used for infection experiment along with GAKS cells. 26291491 11 111 contain possessed 1745:1753 arg1 cells 1733:1737 HeLa cells 1728:1737 HeLa cells which possessed lower amount of α2-3 sialo-linkage glycoprotein 1728:1801 To confirm the significance of α2-3 sialo-linkage desialylation for E. tarda infection, HeLa cells which possessed lower amount of α2-3 sialo-linkage glycoprotein were used for infection experiment along with GAKS cells. 26291491 10 112 theme further 1520:1526 arg1 evidence 1528:1535 further evidence that α2-3 sialo-linkage of the N-linked glycoproteins was the most plausible target of NanA sialidase 1520:1637 further evidence that α2-3 sialo-linkage of the N-linked glycoproteins was the most plausible target of NanA sialidase 1520:1637 Lectin staining of cell surface glycoprotein provided further evidence that α2-3 sialo-linkage of the N-linked glycoproteins was the most plausible target of NanA sialidase. 26291491 3 113 theme tarda 430:434 arg1 infection 436:444 E. tarda infection 427:444 E. tarda infection 427:444 Recently, the relationship of NanA sialidase activity to E. tarda infection has been reported, however, the mechanism with which sialidase NanA aids the pathogenicity of E. tarda remained unclear. 26291491 13 114 theme mannose 2126:2132 arg1 chains 2145:2150 mannose containing chains 2126:2150 mannose containing chains 2126:2150 Furthermore, E. tarda infection was significantly inhibited by mannose pretreatment suggesting that the bacterium potentially recognizes and binds to mannose or mannose containing chains following desialylation. 26291491 9 115 theme sialo-linked 1378:1389 arg1 glycoproteins 1391:1403 α2-3 sialo-linked glycoproteins 1373:1403 α2-3 sialo-linked glycoproteins 1373:1403 Supporting this finding, intact GAKS cell membrane exposed to recombinant NanA showed changes of glycoconjugates only in α2-3 sialo-linked glycoproteins, but not in glycolipids and α2-6 sialo-linked glycoproteins. 26291491 8 116 link linked 1202:1207 arg1 acid 1216:1219 α2-3 linked sialic acid 1197:1219 α2-3 linked sialic acid carrying sialoglycoconjugates 1197:1249 Among the natural substrates, NanA exhibited the highest activity towards 3-sialyllactose, α2-3 linked sialic acid carrying sialoglycoconjugates. 26291491 8 116 link linked 1202:1207 arg1 3-sialyllactose 1180:1194 3-sialyllactose 1180:1194 3-sialyllactose 1180:1194 Among the natural substrates, NanA exhibited the highest activity towards 3-sialyllactose, α2-3 linked sialic acid carrying sialoglycoconjugates. 26291491 14 117 gly glycoproteins 2270:2282 arg1 glycoproteins 2270:2282 desialylate α2-3 glycoproteins 2253:2282 desialylate α2-3 glycoproteins 2253:2282 Together, these results suggest that E. tarda may employ endogenous NanA to desialylate α2-3 glycoproteins on host cells, thus revealing one of the potential binding molecules during infection. 26291491 11 118 theme α2-3 1771:1774 arg1 glycoprotein 1790:1801 α2-3 sialo-linkage glycoprotein 1771:1801 α2-3 sialo-linkage glycoprotein 1771:1801 To confirm the significance of α2-3 sialo-linkage desialylation for E. tarda infection, HeLa cells which possessed lower amount of α2-3 sialo-linkage glycoprotein were used for infection experiment along with GAKS cells. 26291491 14 119 theme binding 2335:2341 arg1 molecules 2343:2351 the potential binding molecules 2321:2351 the potential binding molecules during infection 2321:2368 Together, these results suggest that E. tarda may employ endogenous NanA to desialylate α2-3 glycoproteins on host cells, thus revealing one of the potential binding molecules during infection. 26291491 6 120 theme sialidase 864:872 arg1 tarda 895:899 sialidase inhibitor treated E. tarda 864:899 sialidase inhibitor treated E. tarda 864:899 Moreover, sialidase inhibitor treated E. tarda showed a significantly reduced ability to infect GAKS cells. 26291491 5 121 theme recombinant 782:792 arg1 NanA 794:797 recombinant NanA 782:797 recombinant NanA 782:797 GAKS cell pretreated with recombinant NanA showed increased susceptibility to E. tarda infection. 26291491 3 122 theme sialidase 405:413 arg1 activity 415:422 NanA sialidase activity 400:422 NanA sialidase activity 400:422 Recently, the relationship of NanA sialidase activity to E. tarda infection has been reported, however, the mechanism with which sialidase NanA aids the pathogenicity of E. tarda remained unclear. 26291491 2 123 theme sialic 335:340 arg1 acids 342:346 sialic acids 335:346 sialic acids 335:346 Sialidase NanA expressed endogenously in E. tarda is glycosidase removing sialic acids from glycoconjugates. 26291491 0 124 link linked 48:53 arg1 acid 62:65 α2-3 linked sialic acid 43:65 α2-3 linked sialic acid of host cell surface N-linked glycoprotein 43:108 Recombinant sialidase NanA (rNanA) cleaves α2-3 linked sialic acid of host cell surface N-linked glycoprotein to promote Edwardsiella tarda infection. 26291491 10 125 theme glycoproteins 1577:1589 arg1 sialo-linkage 1547:1559 α2-3 sialo-linkage 1542:1559 α2-3 sialo-linkage of the N-linked glycoproteins 1542:1589 Lectin staining of cell surface glycoprotein provided further evidence that α2-3 sialo-linkage of the N-linked glycoproteins was the most plausible target of NanA sialidase. 26291491 10 125 theme glycoproteins 1577:1589 arg1 target 1614:1619 the most plausible target 1595:1619 the most plausible target of NanA sialidase 1595:1637 Lectin staining of cell surface glycoprotein provided further evidence that α2-3 sialo-linkage of the N-linked glycoproteins was the most plausible target of NanA sialidase. 26291491 11 126 theme glycoprotein 1790:1801 arg1 amount 1761:1766 lower amount 1755:1766 lower amount of α2-3 sialo-linkage glycoprotein 1755:1801 To confirm the significance of α2-3 sialo-linkage desialylation for E. tarda infection, HeLa cells which possessed lower amount of α2-3 sialo-linkage glycoprotein were used for infection experiment along with GAKS cells. 26291491 11 126 theme glycoprotein 1790:1801 arg1 glycoprotein 1790:1801 α2-3 sialo-linkage glycoprotein 1771:1801 α2-3 sialo-linkage glycoprotein 1771:1801 To confirm the significance of α2-3 sialo-linkage desialylation for E. tarda infection, HeLa cells which possessed lower amount of α2-3 sialo-linkage glycoprotein were used for infection experiment along with GAKS cells. 26291491 9 127 theme α2-6 1433:1436 arg1 glycoproteins 1451:1463 α2-6 sialo-linked glycoproteins 1433:1463 α2-6 sialo-linked glycoproteins 1433:1463 Supporting this finding, intact GAKS cell membrane exposed to recombinant NanA showed changes of glycoconjugates only in α2-3 sialo-linked glycoproteins, but not in glycolipids and α2-6 sialo-linked glycoproteins. 26291491 11 128 theme sialo-linkage 1676:1688 arg1 desialylation 1690:1702 α2-3 sialo-linkage desialylation 1671:1702 α2-3 sialo-linkage desialylation 1671:1702 To confirm the significance of α2-3 sialo-linkage desialylation for E. tarda infection, HeLa cells which possessed lower amount of α2-3 sialo-linkage glycoprotein were used for infection experiment along with GAKS cells. 25236489 0 0 theme inhibitory 175:184 arg1 responses 186:194 growth inhibitory responses 168:194 growth inhibitory responses in rabbits 168:205 Detailed functional characterization of glycosylated and nonglycosylated variants of malaria vaccine candidate PfAMA1 produced in Nicotiana benthamiana and analysis of growth inhibitory responses in rabbits. 25236489 4 1 theme negative 620:627 arg1 impact 629:634 any potential negative impact 606:634 any potential negative impact of N-glycosylation 606:653 To prevent any potential negative impact of N-glycosylation, the recognition sites have been knocked out in most PfAMA1 variants expressed in eukaryotic hosts. 25236489 6 2 from benthamiana 994:1004 arg1 characterization 1023:1038 its detailed characterization 1010:1038 its detailed characterization in terms of yield, integrity and protective efficacy 1010:1091 We describe the production of glycosylated and nonglycosylated PfAMA1 in Nicotiana benthamiana and its detailed characterization in terms of yield, integrity and protective efficacy. 25236489 6 2 from benthamiana 994:1004 arg1 production 927:936 the production 923:936 the production of glycosylated and nonglycosylated PfAMA1 in Nicotiana benthamiana 923:1004 We describe the production of glycosylated and nonglycosylated PfAMA1 in Nicotiana benthamiana and its detailed characterization in terms of yield, integrity and protective efficacy. 25236489 11 3 theme transient 1951:1959 arg1 systems 1972:1978 plant transient expression systems 1945:1978 plant transient expression systems 1945:1978 These results highlight the potential of plant transient expression systems as a production platform for vaccine candidates. 25236489 1 4 theme Plasmodium 276:285 arg1 falciparum 287:296 Plasmodium falciparum 276:296 the Plasmodium falciparum apical membrane antigen 1 (PfAMA1) 272:331 One of the most promising malaria vaccine candidate antigens is the Plasmodium falciparum apical membrane antigen 1 (PfAMA1). 25236489 3 5 theme post-translational 530:547 arg1 modification 549:560 a post-translational modification 528:560 a post-translational modification that is absent in P. falciparum 528:592 PfAMA1 contains up to six recognition sites for N-linked glycosylation, a post-translational modification that is absent in P. falciparum. 25236489 3 5 theme post-translational 530:547 arg1 absent 570:575 absent 570:575 absent 570:575 PfAMA1 contains up to six recognition sites for N-linked glycosylation, a post-translational modification that is absent in P. falciparum. 25236489 3 5 theme post-translational 530:547 arg1 sites 494:498 up to six recognition sites 472:498 up to six recognition sites for N-linked glycosylation 472:525 PfAMA1 contains up to six recognition sites for N-linked glycosylation, a post-translational modification that is absent in P. falciparum. 25236489 1 6 theme apical 298:303 arg1 One 208:210 One 208:210 One 208:210 One of the most promising malaria vaccine candidate antigens is the Plasmodium falciparum apical membrane antigen 1 (PfAMA1). 25236489 1 6 theme apical 298:303 arg1 antigens 260:267 the most promising malaria vaccine candidate antigens 215:267 the most promising malaria vaccine candidate antigens 215:267 One of the most promising malaria vaccine candidate antigens is the Plasmodium falciparum apical membrane antigen 1 (PfAMA1). 25236489 1 6 theme apical 298:303 arg1 antigen 314:320 the Plasmodium falciparum apical membrane antigen 1 272:322 the Plasmodium falciparum apical membrane antigen 1 (PfAMA1) 272:331 One of the most promising malaria vaccine candidate antigens is the Plasmodium falciparum apical membrane antigen 1 (PfAMA1). 25236489 1 6 theme apical 298:303 arg1 PfAMA1 325:330 PfAMA1 325:330 PfAMA1 325:330 One of the most promising malaria vaccine candidate antigens is the Plasmodium falciparum apical membrane antigen 1 (PfAMA1). 25236489 6 7 theme nonglycosylated 958:972 arg1 PfAMA1 974:979 glycosylated and nonglycosylated PfAMA1 941:979 glycosylated and nonglycosylated PfAMA1 in Nicotiana benthamiana 941:1004 We describe the production of glycosylated and nonglycosylated PfAMA1 in Nicotiana benthamiana and its detailed characterization in terms of yield, integrity and protective efficacy. 25236489 8 8 theme Pichia 1335:1340 arg1 pastoris 1342:1349 Pichia pastoris 1335:1349 Pichia pastoris 1335:1349 No significant differences between the N. benthamiana and Pichia pastoris PfAMA1 variants were detected in conformation-sensitive ligand-binding studies. 25236489 5 9 theme relevant 874:881 arg1 epitopes 883:890 relevant epitopes 874:890 relevant epitopes 874:890 However, N-linked glycosylation may increase efficacy by improving immunogenicity and/or focusing the response towards relevant epitopes by glycan masking. 25236489 10 10 used used 1851:1854 arg2 glycosylation 1830:1842 glycosylation 1830:1842 glycosylation 1830:1842 Competition assays indicated that a number of epitopes were shielded from immune recognition by N-glycans, warranting further studies to determine how glycosylation can be used for the directed targeting of immune responses. 25236489 6 11 theme glycosylated 941:952 arg1 PfAMA1 974:979 glycosylated and nonglycosylated PfAMA1 941:979 glycosylated and nonglycosylated PfAMA1 in Nicotiana benthamiana 941:1004 We describe the production of glycosylated and nonglycosylated PfAMA1 in Nicotiana benthamiana and its detailed characterization in terms of yield, integrity and protective efficacy. 25236489 9 12 theme × 1453:1453 arg1 titres 1440:1445 Specific titres 1431:1445 Specific titres of >2 × 10(6) 1431:1459 Specific titres of >2 × 10(6) were induced in rabbits, and strong reactivity with P. falciparum schizonts was observed in immunofluorescence assays, as well as up to 100% parasite growth inhibition for both variants, with IC₅₀ values of ~35 μg/mL. 25236489 4 13 theme PfAMA1 708:713 arg1 variants 715:722 most PfAMA1 variants 703:722 most PfAMA1 variants expressed in eukaryotic hosts 703:752 To prevent any potential negative impact of N-glycosylation, the recognition sites have been knocked out in most PfAMA1 variants expressed in eukaryotic hosts. 25236489 9 14 dep P. 1513:1514 arg1 falciparum 1516:1525 falciparum 1516:1525 falciparum 1516:1525 Specific titres of >2 × 10(6) were induced in rabbits, and strong reactivity with P. falciparum schizonts was observed in immunofluorescence assays, as well as up to 100% parasite growth inhibition for both variants, with IC₅₀ values of ~35 μg/mL. 25236489 6 15 theme yield 1052:1056 arg1 terms 1043:1047 terms 1043:1047 terms of yield, integrity and protective efficacy 1043:1091 We describe the production of glycosylated and nonglycosylated PfAMA1 in Nicotiana benthamiana and its detailed characterization in terms of yield, integrity and protective efficacy. 25236489 6 16 from production 927:936 arg1 benthamiana 994:1004 Nicotiana benthamiana 984:1004 Nicotiana benthamiana 984:1004 We describe the production of glycosylated and nonglycosylated PfAMA1 in Nicotiana benthamiana and its detailed characterization in terms of yield, integrity and protective efficacy. 25236489 6 16 from production 927:936 arg1 terms 1043:1047 terms 1043:1047 terms of yield, integrity and protective efficacy 1043:1091 We describe the production of glycosylated and nonglycosylated PfAMA1 in Nicotiana benthamiana and its detailed characterization in terms of yield, integrity and protective efficacy. 25236489 7 17 theme fresh 1153:1157 arg1 levels 1135:1140 high levels 1130:1140 high levels (>510 μg/g fresh leaf weight) 1130:1170 Both PfAMA1 variants accumulated to high levels (>510 μg/g fresh leaf weight) after transient expression, and high-mannose-type N-glycans were confirmed for the glycosylated variant. 25236489 7 17 theme fresh 1153:1157 arg1 weight 1164:1169 >510 μg/g fresh leaf weight 1143:1169 >510 μg/g fresh leaf weight 1143:1169 Both PfAMA1 variants accumulated to high levels (>510 μg/g fresh leaf weight) after transient expression, and high-mannose-type N-glycans were confirmed for the glycosylated variant. 25236489 0 18 from responses 186:194 arg1 rabbits 199:205 rabbits 199:205 rabbits 199:205 Detailed functional characterization of glycosylated and nonglycosylated variants of malaria vaccine candidate PfAMA1 produced in Nicotiana benthamiana and analysis of growth inhibitory responses in rabbits. 25236489 7 19 theme PfAMA1 1099:1104 arg1 variants 1106:1113 Both PfAMA1 variants 1094:1113 Both PfAMA1 variants 1094:1113 Both PfAMA1 variants accumulated to high levels (>510 μg/g fresh leaf weight) after transient expression, and high-mannose-type N-glycans were confirmed for the glycosylated variant. 25236489 1 20 theme malaria 234:240 arg1 antigens 260:267 the most promising malaria vaccine candidate antigens 215:267 the most promising malaria vaccine candidate antigens 215:267 One of the most promising malaria vaccine candidate antigens is the Plasmodium falciparum apical membrane antigen 1 (PfAMA1). 25236489 8 21 theme benthamiana 1319:1329 arg1 variants 1358:1365 the N. benthamiana and Pichia pastoris PfAMA1 variants 1312:1365 the N. benthamiana and Pichia pastoris PfAMA1 variants 1312:1365 No significant differences between the N. benthamiana and Pichia pastoris PfAMA1 variants were detected in conformation-sensitive ligand-binding studies. 25236489 3 22 link N-linked 504:511 arg1 glycosylation 513:525 N-linked glycosylation 504:525 N-linked glycosylation 504:525 PfAMA1 contains up to six recognition sites for N-linked glycosylation, a post-translational modification that is absent in P. falciparum. 25236489 8 23 theme ligand-binding 1407:1420 arg1 studies 1422:1428 conformation-sensitive ligand-binding studies 1384:1428 conformation-sensitive ligand-binding studies 1384:1428 No significant differences between the N. benthamiana and Pichia pastoris PfAMA1 variants were detected in conformation-sensitive ligand-binding studies. 25236489 10 24 theme Competition 1679:1689 arg1 assays 1691:1696 Competition assays 1679:1696 Competition assays 1679:1696 Competition assays indicated that a number of epitopes were shielded from immune recognition by N-glycans, warranting further studies to determine how glycosylation can be used for the directed targeting of immune responses. 25236489 0 25 theme growth 168:173 arg1 responses 186:194 growth inhibitory responses 168:194 growth inhibitory responses in rabbits 168:205 Detailed functional characterization of glycosylated and nonglycosylated variants of malaria vaccine candidate PfAMA1 produced in Nicotiana benthamiana and analysis of growth inhibitory responses in rabbits. 25236489 10 26 theme directed 1864:1871 arg1 targeting 1873:1881 the directed targeting 1860:1881 the directed targeting of immune responses 1860:1901 Competition assays indicated that a number of epitopes were shielded from immune recognition by N-glycans, warranting further studies to determine how glycosylation can be used for the directed targeting of immune responses. 25236489 9 27 dep inhibition 1618:1627 arg1 % 1600:1600 % 1600:1600 % 1600:1600 Specific titres of >2 × 10(6) were induced in rabbits, and strong reactivity with P. falciparum schizonts was observed in immunofluorescence assays, as well as up to 100% parasite growth inhibition for both variants, with IC₅₀ values of ~35 μg/mL. 25236489 0 28 theme responses 186:194 arg1 analysis 156:163 analysis 156:163 analysis of growth inhibitory responses in rabbits 156:205 Detailed functional characterization of glycosylated and nonglycosylated variants of malaria vaccine candidate PfAMA1 produced in Nicotiana benthamiana and analysis of growth inhibitory responses in rabbits. 25236489 0 28 theme responses 186:194 arg1 benthamiana 140:150 Nicotiana benthamiana 130:150 Nicotiana benthamiana 130:150 Detailed functional characterization of glycosylated and nonglycosylated variants of malaria vaccine candidate PfAMA1 produced in Nicotiana benthamiana and analysis of growth inhibitory responses in rabbits. 25236489 11 29 theme production 1985:1994 arg1 potential 1932:1940 the potential 1928:1940 the potential of plant transient expression systems 1928:1978 These results highlight the potential of plant transient expression systems as a production platform for vaccine candidates. 25236489 11 29 theme production 1985:1994 arg1 platform 1996:2003 a production platform 1983:2003 a production platform for vaccine candidates 1983:2026 These results highlight the potential of plant transient expression systems as a production platform for vaccine candidates. 25236489 9 30 theme P. 1513:1514 arg1 schizonts 1527:1535 P. falciparum schizonts 1513:1535 P. falciparum schizonts 1513:1535 Specific titres of >2 × 10(6) were induced in rabbits, and strong reactivity with P. falciparum schizonts was observed in immunofluorescence assays, as well as up to 100% parasite growth inhibition for both variants, with IC₅₀ values of ~35 μg/mL. 25236489 10 31 theme responses 1893:1901 arg1 targeting 1873:1881 the directed targeting 1860:1881 the directed targeting of immune responses 1860:1901 Competition assays indicated that a number of epitopes were shielded from immune recognition by N-glycans, warranting further studies to determine how glycosylation can be used for the directed targeting of immune responses. 25236489 4 32 theme eukaryotic 737:746 arg1 hosts 748:752 eukaryotic hosts 737:752 eukaryotic hosts 737:752 To prevent any potential negative impact of N-glycosylation, the recognition sites have been knocked out in most PfAMA1 variants expressed in eukaryotic hosts. 25236489 0 33 theme vaccine 93:99 arg1 PfAMA1 111:116 malaria vaccine candidate PfAMA1 85:116 malaria vaccine candidate PfAMA1 85:116 Detailed functional characterization of glycosylated and nonglycosylated variants of malaria vaccine candidate PfAMA1 produced in Nicotiana benthamiana and analysis of growth inhibitory responses in rabbits. 25236489 9 34 theme growth 1611:1616 arg1 inhibition 1618:1627 up to 100% parasite growth inhibition 1591:1627 up to 100% parasite growth inhibition for both variants 1591:1645 Specific titres of >2 × 10(6) were induced in rabbits, and strong reactivity with P. falciparum schizonts was observed in immunofluorescence assays, as well as up to 100% parasite growth inhibition for both variants, with IC₅₀ values of ~35 μg/mL. 25236489 6 35 theme protective 1073:1082 arg1 efficacy 1084:1091 protective efficacy 1073:1091 protective efficacy 1073:1091 We describe the production of glycosylated and nonglycosylated PfAMA1 in Nicotiana benthamiana and its detailed characterization in terms of yield, integrity and protective efficacy. 25236489 3 36 from falciparum 583:592 arg1 modification 549:560 a post-translational modification 528:560 a post-translational modification that is absent in P. falciparum 528:592 PfAMA1 contains up to six recognition sites for N-linked glycosylation, a post-translational modification that is absent in P. falciparum. 25236489 3 36 from falciparum 583:592 arg1 absent 570:575 absent 570:575 absent 570:575 PfAMA1 contains up to six recognition sites for N-linked glycosylation, a post-translational modification that is absent in P. falciparum. 25236489 3 36 from falciparum 583:592 arg1 sites 494:498 up to six recognition sites 472:498 up to six recognition sites for N-linked glycosylation 472:525 PfAMA1 contains up to six recognition sites for N-linked glycosylation, a post-translational modification that is absent in P. falciparum. 25236489 0 37 theme PfAMA1 111:116 arg1 variants 73:80 glycosylated and nonglycosylated variants 40:80 glycosylated and nonglycosylated variants of malaria vaccine candidate PfAMA1 40:116 Detailed functional characterization of glycosylated and nonglycosylated variants of malaria vaccine candidate PfAMA1 produced in Nicotiana benthamiana and analysis of growth inhibitory responses in rabbits. 25236489 9 38 theme Specific 1431:1438 arg1 titres 1440:1445 Specific titres 1431:1445 Specific titres of >2 × 10(6) 1431:1459 Specific titres of >2 × 10(6) were induced in rabbits, and strong reactivity with P. falciparum schizonts was observed in immunofluorescence assays, as well as up to 100% parasite growth inhibition for both variants, with IC₅₀ values of ~35 μg/mL. 25236489 6 39 theme integrity 1059:1067 arg1 terms 1043:1047 terms 1043:1047 terms of yield, integrity and protective efficacy 1043:1091 We describe the production of glycosylated and nonglycosylated PfAMA1 in Nicotiana benthamiana and its detailed characterization in terms of yield, integrity and protective efficacy. 25236489 2 40 theme growth 418:423 arg1 responses 445:453 strong parasite growth inhibitory antibody responses 402:453 strong parasite growth inhibitory antibody responses 402:453 Several studies have shown that this blood-stage antigen can induce strong parasite growth inhibitory antibody responses. 25236489 11 41 theme vaccine 2009:2015 arg1 candidates 2017:2026 vaccine candidates 2009:2026 vaccine candidates 2009:2026 These results highlight the potential of plant transient expression systems as a production platform for vaccine candidates. 25236489 2 42 theme strong 402:407 arg1 responses 445:453 strong parasite growth inhibitory antibody responses 402:453 strong parasite growth inhibitory antibody responses 402:453 Several studies have shown that this blood-stage antigen can induce strong parasite growth inhibitory antibody responses. 25236489 0 43 theme Detailed 0:7 arg1 characterization 20:35 Detailed functional characterization 0:35 Detailed functional characterization of glycosylated and nonglycosylated variants of malaria vaccine candidate PfAMA1 0:116 Detailed functional characterization of glycosylated and nonglycosylated variants of malaria vaccine candidate PfAMA1 produced in Nicotiana benthamiana and analysis of growth inhibitory responses in rabbits. 25236489 1 44 theme membrane 305:312 arg1 One 208:210 One 208:210 One 208:210 One of the most promising malaria vaccine candidate antigens is the Plasmodium falciparum apical membrane antigen 1 (PfAMA1). 25236489 1 44 theme membrane 305:312 arg1 antigens 260:267 the most promising malaria vaccine candidate antigens 215:267 the most promising malaria vaccine candidate antigens 215:267 One of the most promising malaria vaccine candidate antigens is the Plasmodium falciparum apical membrane antigen 1 (PfAMA1). 25236489 1 44 theme membrane 305:312 arg1 antigen 314:320 the Plasmodium falciparum apical membrane antigen 1 272:322 the Plasmodium falciparum apical membrane antigen 1 (PfAMA1) 272:331 One of the most promising malaria vaccine candidate antigens is the Plasmodium falciparum apical membrane antigen 1 (PfAMA1). 25236489 1 44 theme membrane 305:312 arg1 PfAMA1 325:330 PfAMA1 325:330 PfAMA1 325:330 One of the most promising malaria vaccine candidate antigens is the Plasmodium falciparum apical membrane antigen 1 (PfAMA1). 25236489 9 45 dep 100 1597:1599 arg1 to 1594:1595 to 1594:1595 to 1594:1595 Specific titres of >2 × 10(6) were induced in rabbits, and strong reactivity with P. falciparum schizonts was observed in immunofluorescence assays, as well as up to 100% parasite growth inhibition for both variants, with IC₅₀ values of ~35 μg/mL. 25236489 10 46 theme immune 1753:1758 arg1 recognition 1760:1770 immune recognition 1753:1770 immune recognition by N-glycans 1753:1783 Competition assays indicated that a number of epitopes were shielded from immune recognition by N-glycans, warranting further studies to determine how glycosylation can be used for the directed targeting of immune responses. 25236489 0 47 from rabbits 199:205 arg1 analysis 156:163 analysis 156:163 analysis of growth inhibitory responses in rabbits 156:205 Detailed functional characterization of glycosylated and nonglycosylated variants of malaria vaccine candidate PfAMA1 produced in Nicotiana benthamiana and analysis of growth inhibitory responses in rabbits. 25236489 0 47 from rabbits 199:205 arg1 benthamiana 140:150 Nicotiana benthamiana 130:150 Nicotiana benthamiana 130:150 Detailed functional characterization of glycosylated and nonglycosylated variants of malaria vaccine candidate PfAMA1 produced in Nicotiana benthamiana and analysis of growth inhibitory responses in rabbits. 25236489 2 48 theme antibody 436:443 arg1 responses 445:453 strong parasite growth inhibitory antibody responses 402:453 strong parasite growth inhibitory antibody responses 402:453 Several studies have shown that this blood-stage antigen can induce strong parasite growth inhibitory antibody responses. 25236489 0 49 theme glycosylated 40:51 arg1 variants 73:80 glycosylated and nonglycosylated variants 40:80 glycosylated and nonglycosylated variants of malaria vaccine candidate PfAMA1 40:116 Detailed functional characterization of glycosylated and nonglycosylated variants of malaria vaccine candidate PfAMA1 produced in Nicotiana benthamiana and analysis of growth inhibitory responses in rabbits. 25236489 0 50 theme nonglycosylated 57:71 arg1 variants 73:80 glycosylated and nonglycosylated variants 40:80 glycosylated and nonglycosylated variants of malaria vaccine candidate PfAMA1 40:116 Detailed functional characterization of glycosylated and nonglycosylated variants of malaria vaccine candidate PfAMA1 produced in Nicotiana benthamiana and analysis of growth inhibitory responses in rabbits. 25236489 11 51 theme plant 1945:1949 arg1 systems 1972:1978 plant transient expression systems 1945:1978 plant transient expression systems 1945:1978 These results highlight the potential of plant transient expression systems as a production platform for vaccine candidates. 25236489 3 52 theme N-linked 504:511 arg1 glycosylation 513:525 N-linked glycosylation 504:525 N-linked glycosylation 504:525 PfAMA1 contains up to six recognition sites for N-linked glycosylation, a post-translational modification that is absent in P. falciparum. 25236489 1 53 theme vaccine 242:248 arg1 antigens 260:267 the most promising malaria vaccine candidate antigens 215:267 the most promising malaria vaccine candidate antigens 215:267 One of the most promising malaria vaccine candidate antigens is the Plasmodium falciparum apical membrane antigen 1 (PfAMA1). 25236489 4 54 theme N-glycosylation 639:653 arg1 impact 629:634 any potential negative impact 606:634 any potential negative impact of N-glycosylation 606:653 To prevent any potential negative impact of N-glycosylation, the recognition sites have been knocked out in most PfAMA1 variants expressed in eukaryotic hosts. 25236489 2 55 theme inhibitory 425:434 arg1 responses 445:453 strong parasite growth inhibitory antibody responses 402:453 strong parasite growth inhibitory antibody responses 402:453 Several studies have shown that this blood-stage antigen can induce strong parasite growth inhibitory antibody responses. 25236489 11 56 theme expression 1961:1970 arg1 systems 1972:1978 plant transient expression systems 1945:1978 plant transient expression systems 1945:1978 These results highlight the potential of plant transient expression systems as a production platform for vaccine candidates. 25236489 1 57 theme antigens 260:267 arg1 One 208:210 One 208:210 One 208:210 One of the most promising malaria vaccine candidate antigens is the Plasmodium falciparum apical membrane antigen 1 (PfAMA1). 25236489 1 57 theme antigens 260:267 arg1 antigens 260:267 the most promising malaria vaccine candidate antigens 215:267 the most promising malaria vaccine candidate antigens 215:267 One of the most promising malaria vaccine candidate antigens is the Plasmodium falciparum apical membrane antigen 1 (PfAMA1). 25236489 1 57 theme antigens 260:267 arg1 antigen 314:320 the Plasmodium falciparum apical membrane antigen 1 272:322 the Plasmodium falciparum apical membrane antigen 1 (PfAMA1) 272:331 One of the most promising malaria vaccine candidate antigens is the Plasmodium falciparum apical membrane antigen 1 (PfAMA1). 25236489 7 58 theme high-mannose-type 1204:1220 arg1 N-glycans 1222:1230 high-mannose-type N-glycans 1204:1230 high-mannose-type N-glycans 1204:1230 Both PfAMA1 variants accumulated to high levels (>510 μg/g fresh leaf weight) after transient expression, and high-mannose-type N-glycans were confirmed for the glycosylated variant. 25236489 0 59 from benthamiana 140:150 arg1 rabbits 199:205 rabbits 199:205 rabbits 199:205 Detailed functional characterization of glycosylated and nonglycosylated variants of malaria vaccine candidate PfAMA1 produced in Nicotiana benthamiana and analysis of growth inhibitory responses in rabbits. 25236489 2 60 theme blood-stage 371:381 arg1 antigen 383:389 this blood-stage antigen 366:389 this blood-stage antigen 366:389 Several studies have shown that this blood-stage antigen can induce strong parasite growth inhibitory antibody responses. 25236489 6 61 theme Nicotiana 984:992 arg1 benthamiana 994:1004 Nicotiana benthamiana 984:1004 Nicotiana benthamiana 984:1004 We describe the production of glycosylated and nonglycosylated PfAMA1 in Nicotiana benthamiana and its detailed characterization in terms of yield, integrity and protective efficacy. 25236489 4 62 theme potential 610:618 arg1 impact 629:634 any potential negative impact 606:634 any potential negative impact of N-glycosylation 606:653 To prevent any potential negative impact of N-glycosylation, the recognition sites have been knocked out in most PfAMA1 variants expressed in eukaryotic hosts. 25236489 7 63 theme transient 1178:1186 arg1 expression 1188:1197 transient expression 1178:1197 transient expression 1178:1197 Both PfAMA1 variants accumulated to high levels (>510 μg/g fresh leaf weight) after transient expression, and high-mannose-type N-glycans were confirmed for the glycosylated variant. 25236489 1 64 theme falciparum 287:296 arg1 One 208:210 One 208:210 One 208:210 One of the most promising malaria vaccine candidate antigens is the Plasmodium falciparum apical membrane antigen 1 (PfAMA1). 25236489 1 64 theme falciparum 287:296 arg1 antigens 260:267 the most promising malaria vaccine candidate antigens 215:267 the most promising malaria vaccine candidate antigens 215:267 One of the most promising malaria vaccine candidate antigens is the Plasmodium falciparum apical membrane antigen 1 (PfAMA1). 25236489 1 64 theme falciparum 287:296 arg1 antigen 314:320 the Plasmodium falciparum apical membrane antigen 1 272:322 the Plasmodium falciparum apical membrane antigen 1 (PfAMA1) 272:331 One of the most promising malaria vaccine candidate antigens is the Plasmodium falciparum apical membrane antigen 1 (PfAMA1). 25236489 1 64 theme falciparum 287:296 arg1 PfAMA1 325:330 PfAMA1 325:330 PfAMA1 325:330 One of the most promising malaria vaccine candidate antigens is the Plasmodium falciparum apical membrane antigen 1 (PfAMA1). 25236489 6 65 theme PfAMA1 974:979 arg1 characterization 1023:1038 its detailed characterization 1010:1038 its detailed characterization in terms of yield, integrity and protective efficacy 1010:1091 We describe the production of glycosylated and nonglycosylated PfAMA1 in Nicotiana benthamiana and its detailed characterization in terms of yield, integrity and protective efficacy. 25236489 6 65 theme PfAMA1 974:979 arg1 production 927:936 the production 923:936 the production of glycosylated and nonglycosylated PfAMA1 in Nicotiana benthamiana 923:1004 We describe the production of glycosylated and nonglycosylated PfAMA1 in Nicotiana benthamiana and its detailed characterization in terms of yield, integrity and protective efficacy. 25236489 9 66 located observed 1541:1548 arg1 assays 1572:1577 immunofluorescence assays 1553:1577 immunofluorescence assays 1553:1577 Specific titres of >2 × 10(6) were induced in rabbits, and strong reactivity with P. falciparum schizonts was observed in immunofluorescence assays, as well as up to 100% parasite growth inhibition for both variants, with IC₅₀ values of ~35 μg/mL. 25236489 9 66 located observed 1541:1548 arg1 inhibition 1618:1627 up to 100% parasite growth inhibition 1591:1627 up to 100% parasite growth inhibition for both variants 1591:1645 Specific titres of >2 × 10(6) were induced in rabbits, and strong reactivity with P. falciparum schizonts was observed in immunofluorescence assays, as well as up to 100% parasite growth inhibition for both variants, with IC₅₀ values of ~35 μg/mL. 25236489 9 66 located observed 1541:1548 arg2 reactivity 1497:1506 strong reactivity 1490:1506 strong reactivity with P. falciparum schizonts 1490:1535 Specific titres of >2 × 10(6) were induced in rabbits, and strong reactivity with P. falciparum schizonts was observed in immunofluorescence assays, as well as up to 100% parasite growth inhibition for both variants, with IC₅₀ values of ~35 μg/mL. 25236489 6 67 from PfAMA1 974:979 arg1 benthamiana 994:1004 Nicotiana benthamiana 984:1004 Nicotiana benthamiana 984:1004 We describe the production of glycosylated and nonglycosylated PfAMA1 in Nicotiana benthamiana and its detailed characterization in terms of yield, integrity and protective efficacy. 25236489 5 68 link N-linked 764:771 arg1 glycosylation 773:785 N-linked glycosylation 764:785 N-linked glycosylation 764:785 However, N-linked glycosylation may increase efficacy by improving immunogenicity and/or focusing the response towards relevant epitopes by glycan masking. 25236489 8 69 theme PfAMA1 1351:1356 arg1 variants 1358:1365 the N. benthamiana and Pichia pastoris PfAMA1 variants 1312:1365 the N. benthamiana and Pichia pastoris PfAMA1 variants 1312:1365 No significant differences between the N. benthamiana and Pichia pastoris PfAMA1 variants were detected in conformation-sensitive ligand-binding studies. 25236489 7 70 theme leaf 1159:1162 arg1 levels 1135:1140 high levels 1130:1140 high levels (>510 μg/g fresh leaf weight) 1130:1170 Both PfAMA1 variants accumulated to high levels (>510 μg/g fresh leaf weight) after transient expression, and high-mannose-type N-glycans were confirmed for the glycosylated variant. 25236489 7 70 theme leaf 1159:1162 arg1 weight 1164:1169 >510 μg/g fresh leaf weight 1143:1169 >510 μg/g fresh leaf weight 1143:1169 Both PfAMA1 variants accumulated to high levels (>510 μg/g fresh leaf weight) after transient expression, and high-mannose-type N-glycans were confirmed for the glycosylated variant. 25236489 2 71 theme Several 334:340 arg1 studies 342:348 Several studies 334:348 Several studies 334:348 Several studies have shown that this blood-stage antigen can induce strong parasite growth inhibitory antibody responses. 25236489 4 72 theme most 703:706 arg1 variants 715:722 most PfAMA1 variants 703:722 most PfAMA1 variants expressed in eukaryotic hosts 703:752 To prevent any potential negative impact of N-glycosylation, the recognition sites have been knocked out in most PfAMA1 variants expressed in eukaryotic hosts. 25236489 7 73 theme μg/g 1148:1151 arg1 levels 1135:1140 high levels 1130:1140 high levels (>510 μg/g fresh leaf weight) 1130:1170 Both PfAMA1 variants accumulated to high levels (>510 μg/g fresh leaf weight) after transient expression, and high-mannose-type N-glycans were confirmed for the glycosylated variant. 25236489 7 73 theme μg/g 1148:1151 arg1 weight 1164:1169 >510 μg/g fresh leaf weight 1143:1169 >510 μg/g fresh leaf weight 1143:1169 Both PfAMA1 variants accumulated to high levels (>510 μg/g fresh leaf weight) after transient expression, and high-mannose-type N-glycans were confirmed for the glycosylated variant. 25236489 5 74 theme glycan 895:900 arg1 masking 902:908 glycan masking 895:908 glycan masking 895:908 However, N-linked glycosylation may increase efficacy by improving immunogenicity and/or focusing the response towards relevant epitopes by glycan masking. 25236489 8 75 theme significant 1280:1290 arg1 differences 1292:1302 No significant differences 1277:1302 No significant differences between the N. benthamiana and Pichia pastoris PfAMA1 variants 1277:1365 No significant differences between the N. benthamiana and Pichia pastoris PfAMA1 variants were detected in conformation-sensitive ligand-binding studies. 25236489 10 76 theme immune 1886:1891 arg1 responses 1893:1901 immune responses 1886:1901 immune responses 1886:1901 Competition assays indicated that a number of epitopes were shielded from immune recognition by N-glycans, warranting further studies to determine how glycosylation can be used for the directed targeting of immune responses. 25236489 8 77 theme pastoris 1342:1349 arg1 variants 1358:1365 the N. benthamiana and Pichia pastoris PfAMA1 variants 1312:1365 the N. benthamiana and Pichia pastoris PfAMA1 variants 1312:1365 No significant differences between the N. benthamiana and Pichia pastoris PfAMA1 variants were detected in conformation-sensitive ligand-binding studies. 25236489 1 78 theme promising 224:232 arg1 antigens 260:267 the most promising malaria vaccine candidate antigens 215:267 the most promising malaria vaccine candidate antigens 215:267 One of the most promising malaria vaccine candidate antigens is the Plasmodium falciparum apical membrane antigen 1 (PfAMA1). 25236489 7 79 theme high 1130:1133 arg1 levels 1135:1140 high levels 1130:1140 high levels (>510 μg/g fresh leaf weight) 1130:1170 Both PfAMA1 variants accumulated to high levels (>510 μg/g fresh leaf weight) after transient expression, and high-mannose-type N-glycans were confirmed for the glycosylated variant. 25236489 7 79 theme high 1130:1133 arg1 weight 1164:1169 >510 μg/g fresh leaf weight 1143:1169 >510 μg/g fresh leaf weight 1143:1169 Both PfAMA1 variants accumulated to high levels (>510 μg/g fresh leaf weight) after transient expression, and high-mannose-type N-glycans were confirmed for the glycosylated variant. 25236489 8 80 theme N. 1316:1317 arg1 benthamiana 1319:1329 N. benthamiana 1316:1329 N. benthamiana 1316:1329 No significant differences between the N. benthamiana and Pichia pastoris PfAMA1 variants were detected in conformation-sensitive ligand-binding studies. 25236489 6 81 theme detailed 1014:1021 arg1 characterization 1023:1038 its detailed characterization 1010:1038 its detailed characterization in terms of yield, integrity and protective efficacy 1010:1091 We describe the production of glycosylated and nonglycosylated PfAMA1 in Nicotiana benthamiana and its detailed characterization in terms of yield, integrity and protective efficacy. 25236489 3 82 contain contains 463:470 arg2 absent 570:575 absent 570:575 absent 570:575 PfAMA1 contains up to six recognition sites for N-linked glycosylation, a post-translational modification that is absent in P. falciparum. 25236489 3 82 contain contains 463:470 arg1 PfAMA1 456:461 PfAMA1 456:461 PfAMA1 456:461 PfAMA1 contains up to six recognition sites for N-linked glycosylation, a post-translational modification that is absent in P. falciparum. 25236489 3 82 contain contains 463:470 arg2 sites 494:498 up to six recognition sites 472:498 up to six recognition sites for N-linked glycosylation 472:525 PfAMA1 contains up to six recognition sites for N-linked glycosylation, a post-translational modification that is absent in P. falciparum. 25236489 3 82 contain contains 463:470 arg2 modification 549:560 a post-translational modification 528:560 a post-translational modification that is absent in P. falciparum 528:592 PfAMA1 contains up to six recognition sites for N-linked glycosylation, a post-translational modification that is absent in P. falciparum. 25236489 8 83 theme conformation-sensitive 1384:1405 arg1 studies 1422:1428 conformation-sensitive ligand-binding studies 1384:1428 conformation-sensitive ligand-binding studies 1384:1428 No significant differences between the N. benthamiana and Pichia pastoris PfAMA1 variants were detected in conformation-sensitive ligand-binding studies. 25236489 6 84 gly nonglycosylated 958:972 arg1 PfAMA1 974:979 glycosylated and nonglycosylated PfAMA1 941:979 glycosylated and nonglycosylated PfAMA1 in Nicotiana benthamiana 941:1004 We describe the production of glycosylated and nonglycosylated PfAMA1 in Nicotiana benthamiana and its detailed characterization in terms of yield, integrity and protective efficacy. 25236489 0 85 gly glycosylated 40:51 arg1 variants 73:80 glycosylated and nonglycosylated variants 40:80 glycosylated and nonglycosylated variants of malaria vaccine candidate PfAMA1 40:116 Detailed functional characterization of glycosylated and nonglycosylated variants of malaria vaccine candidate PfAMA1 produced in Nicotiana benthamiana and analysis of growth inhibitory responses in rabbits. 25236489 6 86 gly glycosylated 941:952 arg1 PfAMA1 974:979 glycosylated and nonglycosylated PfAMA1 941:979 glycosylated and nonglycosylated PfAMA1 in Nicotiana benthamiana 941:1004 We describe the production of glycosylated and nonglycosylated PfAMA1 in Nicotiana benthamiana and its detailed characterization in terms of yield, integrity and protective efficacy. 25236489 0 87 theme malaria 85:91 arg1 PfAMA1 111:116 malaria vaccine candidate PfAMA1 85:116 malaria vaccine candidate PfAMA1 85:116 Detailed functional characterization of glycosylated and nonglycosylated variants of malaria vaccine candidate PfAMA1 produced in Nicotiana benthamiana and analysis of growth inhibitory responses in rabbits. 25236489 9 88 theme immunofluorescence 1553:1570 arg1 assays 1572:1577 immunofluorescence assays 1553:1577 immunofluorescence assays 1553:1577 Specific titres of >2 × 10(6) were induced in rabbits, and strong reactivity with P. falciparum schizonts was observed in immunofluorescence assays, as well as up to 100% parasite growth inhibition for both variants, with IC₅₀ values of ~35 μg/mL. 25236489 3 89 from absent 570:575 arg1 falciparum 583:592 P. falciparum 580:592 P. falciparum 580:592 PfAMA1 contains up to six recognition sites for N-linked glycosylation, a post-translational modification that is absent in P. falciparum. 25236489 0 90 theme candidate 101:109 arg1 PfAMA1 111:116 malaria vaccine candidate PfAMA1 85:116 malaria vaccine candidate PfAMA1 85:116 Detailed functional characterization of glycosylated and nonglycosylated variants of malaria vaccine candidate PfAMA1 produced in Nicotiana benthamiana and analysis of growth inhibitory responses in rabbits. 25236489 9 91 theme parasite 1602:1609 arg1 inhibition 1618:1627 up to 100% parasite growth inhibition 1591:1627 up to 100% parasite growth inhibition for both variants 1591:1645 Specific titres of >2 × 10(6) were induced in rabbits, and strong reactivity with P. falciparum schizonts was observed in immunofluorescence assays, as well as up to 100% parasite growth inhibition for both variants, with IC₅₀ values of ~35 μg/mL. 25236489 6 92 theme efficacy 1084:1091 arg1 terms 1043:1047 terms 1043:1047 terms of yield, integrity and protective efficacy 1043:1091 We describe the production of glycosylated and nonglycosylated PfAMA1 in Nicotiana benthamiana and its detailed characterization in terms of yield, integrity and protective efficacy. 25236489 5 93 theme N-linked 764:771 arg1 glycosylation 773:785 N-linked glycosylation 764:785 N-linked glycosylation 764:785 However, N-linked glycosylation may increase efficacy by improving immunogenicity and/or focusing the response towards relevant epitopes by glycan masking. 25236489 0 94 theme Nicotiana 130:138 arg1 benthamiana 140:150 Nicotiana benthamiana 130:150 Nicotiana benthamiana 130:150 Detailed functional characterization of glycosylated and nonglycosylated variants of malaria vaccine candidate PfAMA1 produced in Nicotiana benthamiana and analysis of growth inhibitory responses in rabbits. 25236489 0 95 from analysis 156:163 arg1 rabbits 199:205 rabbits 199:205 rabbits 199:205 Detailed functional characterization of glycosylated and nonglycosylated variants of malaria vaccine candidate PfAMA1 produced in Nicotiana benthamiana and analysis of growth inhibitory responses in rabbits. 25236489 2 96 theme parasite 409:416 arg1 responses 445:453 strong parasite growth inhibitory antibody responses 402:453 strong parasite growth inhibitory antibody responses 402:453 Several studies have shown that this blood-stage antigen can induce strong parasite growth inhibitory antibody responses. 25236489 0 97 theme functional 9:18 arg1 characterization 20:35 Detailed functional characterization 0:35 Detailed functional characterization of glycosylated and nonglycosylated variants of malaria vaccine candidate PfAMA1 0:116 Detailed functional characterization of glycosylated and nonglycosylated variants of malaria vaccine candidate PfAMA1 produced in Nicotiana benthamiana and analysis of growth inhibitory responses in rabbits. 25236489 9 98 theme >2 1450:1451 arg1 × 1453:1453 >2 × 10(6) 1450:1459 >2 × 10(6) 1450:1459 Specific titres of >2 × 10(6) were induced in rabbits, and strong reactivity with P. falciparum schizonts was observed in immunofluorescence assays, as well as up to 100% parasite growth inhibition for both variants, with IC₅₀ values of ~35 μg/mL. 25236489 8 99 located detected 1372:1379 arg1 studies 1422:1428 conformation-sensitive ligand-binding studies 1384:1428 conformation-sensitive ligand-binding studies 1384:1428 No significant differences between the N. benthamiana and Pichia pastoris PfAMA1 variants were detected in conformation-sensitive ligand-binding studies. 25236489 8 99 located detected 1372:1379 arg2 differences 1292:1302 No significant differences 1277:1302 No significant differences between the N. benthamiana and Pichia pastoris PfAMA1 variants 1277:1365 No significant differences between the N. benthamiana and Pichia pastoris PfAMA1 variants were detected in conformation-sensitive ligand-binding studies. 25236489 9 100 theme IC₅₀ 1653:1656 arg1 values 1658:1663 IC₅₀ values 1653:1663 IC₅₀ values of ~35 μg/mL 1653:1676 Specific titres of >2 × 10(6) were induced in rabbits, and strong reactivity with P. falciparum schizonts was observed in immunofluorescence assays, as well as up to 100% parasite growth inhibition for both variants, with IC₅₀ values of ~35 μg/mL. 25236489 9 101 dep % 1600:1600 arg1 100 1597:1599 100 1597:1599 100 1597:1599 Specific titres of >2 × 10(6) were induced in rabbits, and strong reactivity with P. falciparum schizonts was observed in immunofluorescence assays, as well as up to 100% parasite growth inhibition for both variants, with IC₅₀ values of ~35 μg/mL. 25236489 10 102 theme epitopes 1725:1732 arg1 number 1715:1720 a number 1713:1720 a number of epitopes 1713:1732 Competition assays indicated that a number of epitopes were shielded from immune recognition by N-glycans, warranting further studies to determine how glycosylation can be used for the directed targeting of immune responses. 25236489 3 103 theme recognition 482:492 arg1 modification 549:560 a post-translational modification 528:560 a post-translational modification that is absent in P. falciparum 528:592 PfAMA1 contains up to six recognition sites for N-linked glycosylation, a post-translational modification that is absent in P. falciparum. 25236489 3 103 theme recognition 482:492 arg1 absent 570:575 absent 570:575 absent 570:575 PfAMA1 contains up to six recognition sites for N-linked glycosylation, a post-translational modification that is absent in P. falciparum. 25236489 3 103 theme recognition 482:492 arg1 sites 494:498 up to six recognition sites 472:498 up to six recognition sites for N-linked glycosylation 472:525 PfAMA1 contains up to six recognition sites for N-linked glycosylation, a post-translational modification that is absent in P. falciparum. 25236489 0 104 theme variants 73:80 arg1 characterization 20:35 Detailed functional characterization 0:35 Detailed functional characterization of glycosylated and nonglycosylated variants of malaria vaccine candidate PfAMA1 0:116 Detailed functional characterization of glycosylated and nonglycosylated variants of malaria vaccine candidate PfAMA1 produced in Nicotiana benthamiana and analysis of growth inhibitory responses in rabbits. 25236489 9 105 theme μg/mL 1672:1676 arg1 values 1658:1663 IC₅₀ values 1653:1663 IC₅₀ values of ~35 μg/mL 1653:1676 Specific titres of >2 × 10(6) were induced in rabbits, and strong reactivity with P. falciparum schizonts was observed in immunofluorescence assays, as well as up to 100% parasite growth inhibition for both variants, with IC₅₀ values of ~35 μg/mL. 25236489 9 106 with reactivity 1497:1506 arg1 schizonts 1527:1535 P. falciparum schizonts 1513:1535 P. falciparum schizonts 1513:1535 Specific titres of >2 × 10(6) were induced in rabbits, and strong reactivity with P. falciparum schizonts was observed in immunofluorescence assays, as well as up to 100% parasite growth inhibition for both variants, with IC₅₀ values of ~35 μg/mL. 25236489 3 107 dep six 478:480 arg1 to 475:476 to 475:476 to 475:476 PfAMA1 contains up to six recognition sites for N-linked glycosylation, a post-translational modification that is absent in P. falciparum. 25236489 6 108 from characterization 1023:1038 arg1 benthamiana 994:1004 Nicotiana benthamiana 984:1004 Nicotiana benthamiana 984:1004 We describe the production of glycosylated and nonglycosylated PfAMA1 in Nicotiana benthamiana and its detailed characterization in terms of yield, integrity and protective efficacy. 25236489 6 108 from characterization 1023:1038 arg1 terms 1043:1047 terms 1043:1047 terms of yield, integrity and protective efficacy 1043:1091 We describe the production of glycosylated and nonglycosylated PfAMA1 in Nicotiana benthamiana and its detailed characterization in terms of yield, integrity and protective efficacy. 25236489 7 109 gly glycosylated 1255:1266 arg1 variant 1268:1274 the glycosylated variant 1251:1274 the glycosylated variant 1251:1274 Both PfAMA1 variants accumulated to high levels (>510 μg/g fresh leaf weight) after transient expression, and high-mannose-type N-glycans were confirmed for the glycosylated variant. 25236489 11 110 theme systems 1972:1978 arg1 potential 1932:1940 the potential 1928:1940 the potential of plant transient expression systems 1928:1978 These results highlight the potential of plant transient expression systems as a production platform for vaccine candidates. 25236489 11 110 theme systems 1972:1978 arg1 platform 1996:2003 a production platform 1983:2003 a production platform for vaccine candidates 1983:2026 These results highlight the potential of plant transient expression systems as a production platform for vaccine candidates. 25236489 1 111 theme candidate 250:258 arg1 antigens 260:267 the most promising malaria vaccine candidate antigens 215:267 the most promising malaria vaccine candidate antigens 215:267 One of the most promising malaria vaccine candidate antigens is the Plasmodium falciparum apical membrane antigen 1 (PfAMA1). 25236489 0 112 gly nonglycosylated 57:71 arg1 variants 73:80 glycosylated and nonglycosylated variants 40:80 glycosylated and nonglycosylated variants of malaria vaccine candidate PfAMA1 40:116 Detailed functional characterization of glycosylated and nonglycosylated variants of malaria vaccine candidate PfAMA1 produced in Nicotiana benthamiana and analysis of growth inhibitory responses in rabbits. 25236489 10 113 theme further 1797:1803 arg1 studies 1805:1811 further studies 1797:1811 further studies 1797:1811 Competition assays indicated that a number of epitopes were shielded from immune recognition by N-glycans, warranting further studies to determine how glycosylation can be used for the directed targeting of immune responses. 25236489 4 114 theme recognition 660:670 arg1 sites 672:676 the recognition sites 656:676 the recognition sites 656:676 To prevent any potential negative impact of N-glycosylation, the recognition sites have been knocked out in most PfAMA1 variants expressed in eukaryotic hosts. 25236489 7 115 theme glycosylated 1255:1266 arg1 variant 1268:1274 the glycosylated variant 1251:1274 the glycosylated variant 1251:1274 Both PfAMA1 variants accumulated to high levels (>510 μg/g fresh leaf weight) after transient expression, and high-mannose-type N-glycans were confirmed for the glycosylated variant. 25236489 9 116 theme strong 1490:1495 arg1 reactivity 1497:1506 strong reactivity 1490:1506 strong reactivity with P. falciparum schizonts 1490:1535 Specific titres of >2 × 10(6) were induced in rabbits, and strong reactivity with P. falciparum schizonts was observed in immunofluorescence assays, as well as up to 100% parasite growth inhibition for both variants, with IC₅₀ values of ~35 μg/mL. 28132902 0 0 theme gamma 76:80 arg1 subunit 82:88 the translocon-associated protein (TRAP) gamma subunit 35:88 the translocon-associated protein (TRAP) gamma subunit 35:88 Membrane insertion and topology of the translocon-associated protein (TRAP) gamma subunit. 28132902 1 1 theme eukaryotic 252:261 arg1 cells 263:267 eukaryotic cells 252:267 eukaryotic cells 252:267 Translocon-associated protein (TRAP) complex is intimately associated with the ER translocon for the insertion or translocation of newly synthesised proteins in eukaryotic cells. 28132902 3 2 dep insertion 395:403 arg1 the 382:384 the 382:384 the 382:384 We have investigated the membrane insertion and topology of the multiple-spanning TRAP-γ subunit by glycosylation mapping and green fluorescent protein fusions both in vitro and in cell cultures. 28132902 4 3 theme protein 781:787 arg1 context 758:764 the cellular context 745:764 the cellular context of full-length protein 745:787 Results demonstrate that TRAP-γ has four transmembrane (TM) segments, an Nt/Ct cytosolic orientation and that the less hydrophobic TM segment inserts efficiently into the membrane only in the cellular context of full-length protein. 28132902 0 4 theme subunit 82:88 arg1 topology 23:30 topology 23:30 topology 23:30 Membrane insertion and topology of the translocon-associated protein (TRAP) gamma subunit. 28132902 0 4 theme subunit 82:88 arg1 insertion 9:17 Membrane insertion 0:17 Membrane insertion 0:17 Membrane insertion and topology of the translocon-associated protein (TRAP) gamma subunit. 28132902 4 5 theme full-length 769:779 arg1 protein 781:787 full-length protein 769:787 full-length protein 769:787 Results demonstrate that TRAP-γ has four transmembrane (TM) segments, an Nt/Ct cytosolic orientation and that the less hydrophobic TM segment inserts efficiently into the membrane only in the cellular context of full-length protein. 28132902 4 6 theme TM 613:614 arg1 orientation 646:656 an Nt/Ct cytosolic orientation 627:656 an Nt/Ct cytosolic orientation 627:656 Results demonstrate that TRAP-γ has four transmembrane (TM) segments, an Nt/Ct cytosolic orientation and that the less hydrophobic TM segment inserts efficiently into the membrane only in the cellular context of full-length protein. 28132902 4 6 theme TM 613:614 arg1 segments 617:624 four transmembrane (TM) segments 593:624 four transmembrane (TM) segments 593:624 Results demonstrate that TRAP-γ has four transmembrane (TM) segments, an Nt/Ct cytosolic orientation and that the less hydrophobic TM segment inserts efficiently into the membrane only in the cellular context of full-length protein. 28132902 4 7 theme cytosolic 636:644 arg1 orientation 646:656 an Nt/Ct cytosolic orientation 627:656 an Nt/Ct cytosolic orientation 627:656 Results demonstrate that TRAP-γ has four transmembrane (TM) segments, an Nt/Ct cytosolic orientation and that the less hydrophobic TM segment inserts efficiently into the membrane only in the cellular context of full-length protein. 28132902 4 7 theme cytosolic 636:644 arg1 segments 617:624 four transmembrane (TM) segments 593:624 four transmembrane (TM) segments 593:624 Results demonstrate that TRAP-γ has four transmembrane (TM) segments, an Nt/Ct cytosolic orientation and that the less hydrophobic TM segment inserts efficiently into the membrane only in the cellular context of full-length protein. 28132902 2 8 theme TRAP 274:277 arg1 complex 279:285 The TRAP complex 270:285 The TRAP complex 270:285 The TRAP complex is comprised of three single-spanning and one multiple-spanning subunits. 28132902 4 9 theme TM 688:689 arg1 segment 691:697 the less hydrophobic TM segment 667:697 the less hydrophobic TM segment 667:697 Results demonstrate that TRAP-γ has four transmembrane (TM) segments, an Nt/Ct cytosolic orientation and that the less hydrophobic TM segment inserts efficiently into the membrane only in the cellular context of full-length protein. 28132902 1 10 theme ER 170:171 arg1 translocon 173:182 the ER translocon 166:182 the ER translocon for the insertion or translocation of newly synthesised proteins in eukaryotic cells 166:267 Translocon-associated protein (TRAP) complex is intimately associated with the ER translocon for the insertion or translocation of newly synthesised proteins in eukaryotic cells. 28132902 4 11 contain has 589:591 arg1 TRAP-γ 582:587 TRAP-γ 582:587 TRAP-γ 582:587 Results demonstrate that TRAP-γ has four transmembrane (TM) segments, an Nt/Ct cytosolic orientation and that the less hydrophobic TM segment inserts efficiently into the membrane only in the cellular context of full-length protein. 28132902 4 11 contain has 589:591 arg2 segments 617:624 four transmembrane (TM) segments 593:624 four transmembrane (TM) segments 593:624 Results demonstrate that TRAP-γ has four transmembrane (TM) segments, an Nt/Ct cytosolic orientation and that the less hydrophobic TM segment inserts efficiently into the membrane only in the cellular context of full-length protein. 28132902 4 11 contain has 589:591 arg2 orientation 646:656 an Nt/Ct cytosolic orientation 627:656 an Nt/Ct cytosolic orientation 627:656 Results demonstrate that TRAP-γ has four transmembrane (TM) segments, an Nt/Ct cytosolic orientation and that the less hydrophobic TM segment inserts efficiently into the membrane only in the cellular context of full-length protein. 28132902 3 12 theme TRAP-γ 443:448 arg1 subunit 450:456 the multiple-spanning TRAP-γ subunit 421:456 the multiple-spanning TRAP-γ subunit 421:456 We have investigated the membrane insertion and topology of the multiple-spanning TRAP-γ subunit by glycosylation mapping and green fluorescent protein fusions both in vitro and in cell cultures. 28132902 0 13 theme Membrane 0:7 arg1 insertion 9:17 Membrane insertion 0:17 Membrane insertion 0:17 Membrane insertion and topology of the translocon-associated protein (TRAP) gamma subunit. 28132902 3 14 theme subunit 450:456 arg1 insertion 395:403 membrane insertion 386:403 membrane insertion 386:403 We have investigated the membrane insertion and topology of the multiple-spanning TRAP-γ subunit by glycosylation mapping and green fluorescent protein fusions both in vitro and in cell cultures. 28132902 3 14 theme subunit 450:456 arg1 topology 409:416 topology 409:416 topology 409:416 We have investigated the membrane insertion and topology of the multiple-spanning TRAP-γ subunit by glycosylation mapping and green fluorescent protein fusions both in vitro and in cell cultures. 28132902 1 15 theme Translocon-associated 91:111 arg1 complex 128:134 Translocon-associated protein (TRAP) complex 91:134 Translocon-associated protein (TRAP) complex 91:134 Translocon-associated protein (TRAP) complex is intimately associated with the ER translocon for the insertion or translocation of newly synthesised proteins in eukaryotic cells. 28132902 3 16 theme green 487:491 arg1 fusions 513:519 green fluorescent protein fusions 487:519 green fluorescent protein fusions 487:519 We have investigated the membrane insertion and topology of the multiple-spanning TRAP-γ subunit by glycosylation mapping and green fluorescent protein fusions both in vitro and in cell cultures. 28132902 3 17 theme membrane 386:393 arg1 insertion 395:403 membrane insertion 386:403 membrane insertion 386:403 We have investigated the membrane insertion and topology of the multiple-spanning TRAP-γ subunit by glycosylation mapping and green fluorescent protein fusions both in vitro and in cell cultures. 28132902 3 18 dep both 521:524 arg1 vitro 529:533 vitro 529:533 vitro 529:533 We have investigated the membrane insertion and topology of the multiple-spanning TRAP-γ subunit by glycosylation mapping and green fluorescent protein fusions both in vitro and in cell cultures. 28132902 1 19 theme protein 113:119 arg1 complex 128:134 Translocon-associated protein (TRAP) complex 91:134 Translocon-associated protein (TRAP) complex 91:134 Translocon-associated protein (TRAP) complex is intimately associated with the ER translocon for the insertion or translocation of newly synthesised proteins in eukaryotic cells. 28132902 3 20 theme fluorescent 493:503 arg1 fusions 513:519 green fluorescent protein fusions 487:519 green fluorescent protein fusions 487:519 We have investigated the membrane insertion and topology of the multiple-spanning TRAP-γ subunit by glycosylation mapping and green fluorescent protein fusions both in vitro and in cell cultures. 28132902 4 21 theme hydrophobic 676:686 arg1 segment 691:697 the less hydrophobic TM segment 667:697 the less hydrophobic TM segment 667:697 Results demonstrate that TRAP-γ has four transmembrane (TM) segments, an Nt/Ct cytosolic orientation and that the less hydrophobic TM segment inserts efficiently into the membrane only in the cellular context of full-length protein. 28132902 3 22 theme multiple-spanning 425:441 arg1 subunit 450:456 the multiple-spanning TRAP-γ subunit 421:456 the multiple-spanning TRAP-γ subunit 421:456 We have investigated the membrane insertion and topology of the multiple-spanning TRAP-γ subunit by glycosylation mapping and green fluorescent protein fusions both in vitro and in cell cultures. 28132902 4 23 theme transmembrane 598:610 arg1 orientation 646:656 an Nt/Ct cytosolic orientation 627:656 an Nt/Ct cytosolic orientation 627:656 Results demonstrate that TRAP-γ has four transmembrane (TM) segments, an Nt/Ct cytosolic orientation and that the less hydrophobic TM segment inserts efficiently into the membrane only in the cellular context of full-length protein. 28132902 4 23 theme transmembrane 598:610 arg1 segments 617:624 four transmembrane (TM) segments 593:624 four transmembrane (TM) segments 593:624 Results demonstrate that TRAP-γ has four transmembrane (TM) segments, an Nt/Ct cytosolic orientation and that the less hydrophobic TM segment inserts efficiently into the membrane only in the cellular context of full-length protein. 28132902 4 24 theme Nt/Ct 630:634 arg1 orientation 646:656 an Nt/Ct cytosolic orientation 627:656 an Nt/Ct cytosolic orientation 627:656 Results demonstrate that TRAP-γ has four transmembrane (TM) segments, an Nt/Ct cytosolic orientation and that the less hydrophobic TM segment inserts efficiently into the membrane only in the cellular context of full-length protein. 28132902 4 24 theme Nt/Ct 630:634 arg1 segments 617:624 four transmembrane (TM) segments 593:624 four transmembrane (TM) segments 593:624 Results demonstrate that TRAP-γ has four transmembrane (TM) segments, an Nt/Ct cytosolic orientation and that the less hydrophobic TM segment inserts efficiently into the membrane only in the cellular context of full-length protein. 28132902 0 25 theme protein 61:67 arg1 subunit 82:88 the translocon-associated protein (TRAP) gamma subunit 35:88 the translocon-associated protein (TRAP) gamma subunit 35:88 Membrane insertion and topology of the translocon-associated protein (TRAP) gamma subunit. 28132902 1 26 from translocation 205:217 arg1 cells 263:267 eukaryotic cells 252:267 eukaryotic cells 252:267 Translocon-associated protein (TRAP) complex is intimately associated with the ER translocon for the insertion or translocation of newly synthesised proteins in eukaryotic cells. 28132902 0 27 theme translocon-associated 39:59 arg1 subunit 82:88 the translocon-associated protein (TRAP) gamma subunit 35:88 the translocon-associated protein (TRAP) gamma subunit 35:88 Membrane insertion and topology of the translocon-associated protein (TRAP) gamma subunit. 28132902 1 28 theme TRAP 122:125 arg1 complex 128:134 Translocon-associated protein (TRAP) complex 91:134 Translocon-associated protein (TRAP) complex 91:134 Translocon-associated protein (TRAP) complex is intimately associated with the ER translocon for the insertion or translocation of newly synthesised proteins in eukaryotic cells. 28132902 4 29 theme cellular 749:756 arg1 context 758:764 the cellular context 745:764 the cellular context of full-length protein 745:787 Results demonstrate that TRAP-γ has four transmembrane (TM) segments, an Nt/Ct cytosolic orientation and that the less hydrophobic TM segment inserts efficiently into the membrane only in the cellular context of full-length protein. 28132902 3 30 dep mapping 475:481 arg1 both 521:524 both 521:524 both 521:524 We have investigated the membrane insertion and topology of the multiple-spanning TRAP-γ subunit by glycosylation mapping and green fluorescent protein fusions both in vitro and in cell cultures. 28132902 3 30 dep mapping 475:481 arg1 cultures 547:554 cell cultures 542:554 cell cultures 542:554 We have investigated the membrane insertion and topology of the multiple-spanning TRAP-γ subunit by glycosylation mapping and green fluorescent protein fusions both in vitro and in cell cultures. 28132902 1 31 from insertion 192:200 arg1 cells 263:267 eukaryotic cells 252:267 eukaryotic cells 252:267 Translocon-associated protein (TRAP) complex is intimately associated with the ER translocon for the insertion or translocation of newly synthesised proteins in eukaryotic cells. 28132902 2 32 dep single-spanning 309:323 arg1 subunits 351:358 subunits 351:358 subunits 351:358 The TRAP complex is comprised of three single-spanning and one multiple-spanning subunits. 28132902 3 33 theme protein 505:511 arg1 fusions 513:519 green fluorescent protein fusions 487:519 green fluorescent protein fusions 487:519 We have investigated the membrane insertion and topology of the multiple-spanning TRAP-γ subunit by glycosylation mapping and green fluorescent protein fusions both in vitro and in cell cultures. 28132902 0 34 theme TRAP 70:73 arg1 subunit 82:88 the translocon-associated protein (TRAP) gamma subunit 35:88 the translocon-associated protein (TRAP) gamma subunit 35:88 Membrane insertion and topology of the translocon-associated protein (TRAP) gamma subunit. 28132902 3 35 theme glycosylation 461:473 arg1 mapping 475:481 glycosylation mapping 461:481 glycosylation mapping 461:481 We have investigated the membrane insertion and topology of the multiple-spanning TRAP-γ subunit by glycosylation mapping and green fluorescent protein fusions both in vitro and in cell cultures. 28132902 1 36 theme synthesised 228:238 arg1 proteins 240:247 newly synthesised proteins 222:247 newly synthesised proteins 222:247 Translocon-associated protein (TRAP) complex is intimately associated with the ER translocon for the insertion or translocation of newly synthesised proteins in eukaryotic cells. 28132902 1 37 dep insertion 192:200 arg1 the 188:190 the 188:190 the 188:190 Translocon-associated protein (TRAP) complex is intimately associated with the ER translocon for the insertion or translocation of newly synthesised proteins in eukaryotic cells. 28132902 3 38 theme cell 542:545 arg1 cultures 547:554 cell cultures 542:554 cell cultures 542:554 We have investigated the membrane insertion and topology of the multiple-spanning TRAP-γ subunit by glycosylation mapping and green fluorescent protein fusions both in vitro and in cell cultures. 28132902 1 39 theme proteins 240:247 arg1 insertion 192:200 insertion 192:200 insertion 192:200 Translocon-associated protein (TRAP) complex is intimately associated with the ER translocon for the insertion or translocation of newly synthesised proteins in eukaryotic cells. 28132902 1 39 theme proteins 240:247 arg1 translocation 205:217 translocation 205:217 translocation 205:217 Translocon-associated protein (TRAP) complex is intimately associated with the ER translocon for the insertion or translocation of newly synthesised proteins in eukaryotic cells. 26085184 1 0 theme located 126:132 arg1 chaperone 116:124 a lectin chaperone 107:124 a lectin chaperone located in the endoplasmic reticulum (ER) 107:166 Calnexin (CNX), known as a lectin chaperone located in the endoplasmic reticulum (ER), specifically recognizes G1M9GN2-proteins and facilitates their proper folding with the assistance of ERp57 in mammalian cells. 26085184 0 1 from role 12:15 arg1 folding 73:79 Aspergillus oryzae glycoprotein folding 41:79 Aspergillus oryzae glycoprotein folding 41:79 Cooperative role of calnexin and TigA in Aspergillus oryzae glycoprotein folding. 26085184 4 2 theme glycoprotein 807:818 arg1 G1M9GN2-RNase 820:832 a homogeneous monoglucosylated high-mannose-type glycoprotein G1M9GN2-RNase 758:832 a homogeneous monoglucosylated high-mannose-type glycoprotein G1M9GN2-RNase 758:832 For refolding experiments, a homogeneous monoglucosylated high-mannose-type glycoprotein G1M9GN2-RNase was chemoenzymatically synthesized from G1M9GN-oxazoline and GN-RNase. 26085184 1 3 from located 126:132 arg1 reticulum 153:161 the endoplasmic reticulum 137:161 the endoplasmic reticulum (ER) 137:166 Calnexin (CNX), known as a lectin chaperone located in the endoplasmic reticulum (ER), specifically recognizes G1M9GN2-proteins and facilitates their proper folding with the assistance of ERp57 in mammalian cells. 26085184 1 3 from located 126:132 arg1 ER 164:165 ER 164:165 ER 164:165 Calnexin (CNX), known as a lectin chaperone located in the endoplasmic reticulum (ER), specifically recognizes G1M9GN2-proteins and facilitates their proper folding with the assistance of ERp57 in mammalian cells. 26085184 4 4 gly glycoprotein 807:818 arg1 glycoprotein 807:818 a homogeneous monoglucosylated high-mannose-type glycoprotein G1M9GN2-RNase 758:832 a homogeneous monoglucosylated high-mannose-type glycoprotein G1M9GN2-RNase 758:832 For refolding experiments, a homogeneous monoglucosylated high-mannose-type glycoprotein G1M9GN2-RNase was chemoenzymatically synthesized from G1M9GN-oxazoline and GN-RNase. 26085184 5 5 from efficiency 955:964 arg1 presence 973:980 the presence 969:980 the presence of both soluble form of AoCNX and TigA 969:1019 Denatured G1M9GN2-RNase was refolded with highest efficiency in the presence of both soluble form of AoCNX and TigA. 26085184 1 6 theme proper 232:237 arg1 folding 239:245 their proper folding 226:245 their proper folding with the assistance of ERp57 in mammalian cells 226:293 Calnexin (CNX), known as a lectin chaperone located in the endoplasmic reticulum (ER), specifically recognizes G1M9GN2-proteins and facilitates their proper folding with the assistance of ERp57 in mammalian cells. 26085184 3 7 attach derived 634:640 arg1 species 653:659 other species 647:659 other species 647:659 In this study, we found that a protein disulfide isomerase homolog TigA can bind with A. oryzae CNX (AoCNX), which was revealed to specifically recognize monoglucosylated glycans, similarly to CNX derived from other species, and accelerate the folding of G1M9GN2-ribonuclease (RNase) in vitro. 26085184 3 7 attach derived 634:640 arg2 CNX 630:632 CNX 630:632 CNX derived from other species 630:659 In this study, we found that a protein disulfide isomerase homolog TigA can bind with A. oryzae CNX (AoCNX), which was revealed to specifically recognize monoglucosylated glycans, similarly to CNX derived from other species, and accelerate the folding of G1M9GN2-ribonuclease (RNase) in vitro. 26085184 7 8 gly glycoprotein 1260:1271 arg1 glycoprotein 1260:1271 glycoprotein folding process 1260:1287 glycoprotein folding process of A. oryzae 1260:1300 The results suggested that in glycoprotein folding process of A. oryzae, TigA plays a similar role as ERp57 in mammalian cells, as a partner protein of AoCNX. 26085184 6 9 theme protein 1211:1217 arg1 refolding 1219:1227 protein refolding 1211:1227 protein refolding 1211:1227 TigA contains two thioredoxin domains with CGHC motif, mutation analysis of which revealed that the one in N-terminal regions is involved in binding to AoCNX, while the other in catalyzing protein refolding. 26085184 3 10 theme isomerase 486:494 arg1 TigA 504:507 a protein disulfide isomerase homolog TigA 466:507 a protein disulfide isomerase homolog TigA 466:507 In this study, we found that a protein disulfide isomerase homolog TigA can bind with A. oryzae CNX (AoCNX), which was revealed to specifically recognize monoglucosylated glycans, similarly to CNX derived from other species, and accelerate the folding of G1M9GN2-ribonuclease (RNase) in vitro. 26085184 3 11 theme homolog 496:502 arg1 TigA 504:507 a protein disulfide isomerase homolog TigA 466:507 a protein disulfide isomerase homolog TigA 466:507 In this study, we found that a protein disulfide isomerase homolog TigA can bind with A. oryzae CNX (AoCNX), which was revealed to specifically recognize monoglucosylated glycans, similarly to CNX derived from other species, and accelerate the folding of G1M9GN2-ribonuclease (RNase) in vitro. 26085184 0 12 gly glycoprotein 60:71 arg1 glycoprotein 60:71 Aspergillus oryzae glycoprotein folding 41:79 Aspergillus oryzae glycoprotein folding 41:79 Cooperative role of calnexin and TigA in Aspergillus oryzae glycoprotein folding. 26085184 4 13 theme homogeneous 760:770 arg1 G1M9GN2-RNase 820:832 a homogeneous monoglucosylated high-mannose-type glycoprotein G1M9GN2-RNase 758:832 a homogeneous monoglucosylated high-mannose-type glycoprotein G1M9GN2-RNase 758:832 For refolding experiments, a homogeneous monoglucosylated high-mannose-type glycoprotein G1M9GN2-RNase was chemoenzymatically synthesized from G1M9GN-oxazoline and GN-RNase. 26085184 6 14 theme CGHC 1065:1068 arg1 motif 1070:1074 CGHC motif 1065:1074 CGHC motif 1065:1074 TigA contains two thioredoxin domains with CGHC motif, mutation analysis of which revealed that the one in N-terminal regions is involved in binding to AoCNX, while the other in catalyzing protein refolding. 26085184 3 15 theme protein 468:474 arg1 isomerase 486:494 a protein disulfide isomerase 466:494 a protein disulfide isomerase homolog TigA 466:507 In this study, we found that a protein disulfide isomerase homolog TigA can bind with A. oryzae CNX (AoCNX), which was revealed to specifically recognize monoglucosylated glycans, similarly to CNX derived from other species, and accelerate the folding of G1M9GN2-ribonuclease (RNase) in vitro. 26085184 2 16 theme Aspergillus 352:362 arg1 fungus 395:400 a filamentous fungus 381:400 a filamentous fungus widely exploited in biotechnology 381:434 However, it has been left unidentified how CNX works in Aspergillus oryzae, which is a filamentous fungus widely exploited in biotechnology. 26085184 2 16 theme Aspergillus 352:362 arg1 oryzae 364:369 Aspergillus oryzae 352:369 Aspergillus oryzae 352:369 However, it has been left unidentified how CNX works in Aspergillus oryzae, which is a filamentous fungus widely exploited in biotechnology. 26085184 6 17 contain contains 1027:1034 arg2 domains 1052:1058 two thioredoxin domains 1036:1058 two thioredoxin domains 1036:1058 TigA contains two thioredoxin domains with CGHC motif, mutation analysis of which revealed that the one in N-terminal regions is involved in binding to AoCNX, while the other in catalyzing protein refolding. 26085184 6 17 contain contains 1027:1034 arg1 TigA 1022:1025 TigA 1022:1025 TigA 1022:1025 TigA contains two thioredoxin domains with CGHC motif, mutation analysis of which revealed that the one in N-terminal regions is involved in binding to AoCNX, while the other in catalyzing protein refolding. 26085184 3 18 theme disulfide 476:484 arg1 isomerase 486:494 a protein disulfide isomerase 466:494 a protein disulfide isomerase homolog TigA 466:507 In this study, we found that a protein disulfide isomerase homolog TigA can bind with A. oryzae CNX (AoCNX), which was revealed to specifically recognize monoglucosylated glycans, similarly to CNX derived from other species, and accelerate the folding of G1M9GN2-ribonuclease (RNase) in vitro. 26085184 1 19 theme endoplasmic 141:151 arg1 reticulum 153:161 the endoplasmic reticulum 137:161 the endoplasmic reticulum (ER) 137:166 Calnexin (CNX), known as a lectin chaperone located in the endoplasmic reticulum (ER), specifically recognizes G1M9GN2-proteins and facilitates their proper folding with the assistance of ERp57 in mammalian cells. 26085184 1 19 theme endoplasmic 141:151 arg1 ER 164:165 ER 164:165 ER 164:165 Calnexin (CNX), known as a lectin chaperone located in the endoplasmic reticulum (ER), specifically recognizes G1M9GN2-proteins and facilitates their proper folding with the assistance of ERp57 in mammalian cells. 26085184 3 20 theme other 647:651 arg1 species 653:659 other species 647:659 other species 647:659 In this study, we found that a protein disulfide isomerase homolog TigA can bind with A. oryzae CNX (AoCNX), which was revealed to specifically recognize monoglucosylated glycans, similarly to CNX derived from other species, and accelerate the folding of G1M9GN2-ribonuclease (RNase) in vitro. 26085184 4 21 theme high-mannose-type 789:805 arg1 G1M9GN2-RNase 820:832 a homogeneous monoglucosylated high-mannose-type glycoprotein G1M9GN2-RNase 758:832 a homogeneous monoglucosylated high-mannose-type glycoprotein G1M9GN2-RNase 758:832 For refolding experiments, a homogeneous monoglucosylated high-mannose-type glycoprotein G1M9GN2-RNase was chemoenzymatically synthesized from G1M9GN-oxazoline and GN-RNase. 26085184 6 22 theme N-terminal 1129:1138 arg1 regions 1140:1146 N-terminal regions 1129:1146 N-terminal regions 1129:1146 TigA contains two thioredoxin domains with CGHC motif, mutation analysis of which revealed that the one in N-terminal regions is involved in binding to AoCNX, while the other in catalyzing protein refolding. 26085184 6 23 theme domains 1052:1058 arg1 analysis 1086:1093 mutation analysis 1077:1093 mutation analysis 1077:1093 TigA contains two thioredoxin domains with CGHC motif, mutation analysis of which revealed that the one in N-terminal regions is involved in binding to AoCNX, while the other in catalyzing protein refolding. 26085184 0 24 theme Cooperative 0:10 arg1 role 12:15 Cooperative role 0:15 Cooperative role of calnexin and TigA in Aspergillus oryzae glycoprotein folding. 0:80 Cooperative role of calnexin and TigA in Aspergillus oryzae glycoprotein folding. 26085184 1 25 from assistance 256:265 arg1 cells 289:293 mammalian cells 279:293 mammalian cells 279:293 Calnexin (CNX), known as a lectin chaperone located in the endoplasmic reticulum (ER), specifically recognizes G1M9GN2-proteins and facilitates their proper folding with the assistance of ERp57 in mammalian cells. 26085184 6 26 from one 1122:1124 arg1 regions 1140:1146 N-terminal regions 1129:1146 N-terminal regions 1129:1146 TigA contains two thioredoxin domains with CGHC motif, mutation analysis of which revealed that the one in N-terminal regions is involved in binding to AoCNX, while the other in catalyzing protein refolding. 26085184 6 27 theme thioredoxin 1040:1050 arg1 domains 1052:1058 two thioredoxin domains 1036:1058 two thioredoxin domains 1036:1058 TigA contains two thioredoxin domains with CGHC motif, mutation analysis of which revealed that the one in N-terminal regions is involved in binding to AoCNX, while the other in catalyzing protein refolding. 26085184 0 28 theme calnexin 20:27 arg1 role 12:15 Cooperative role 0:15 Cooperative role of calnexin and TigA in Aspergillus oryzae glycoprotein folding. 0:80 Cooperative role of calnexin and TigA in Aspergillus oryzae glycoprotein folding. 26085184 7 29 theme mammalian 1341:1349 arg1 cells 1351:1355 mammalian cells 1341:1355 mammalian cells 1341:1355 The results suggested that in glycoprotein folding process of A. oryzae, TigA plays a similar role as ERp57 in mammalian cells, as a partner protein of AoCNX. 26085184 7 30 theme folding 1273:1279 arg1 process 1281:1287 glycoprotein folding process 1260:1287 glycoprotein folding process of A. oryzae 1260:1300 The results suggested that in glycoprotein folding process of A. oryzae, TigA plays a similar role as ERp57 in mammalian cells, as a partner protein of AoCNX. 26085184 6 31 with domains 1052:1058 arg1 motif 1070:1074 CGHC motif 1065:1074 CGHC motif 1065:1074 TigA contains two thioredoxin domains with CGHC motif, mutation analysis of which revealed that the one in N-terminal regions is involved in binding to AoCNX, while the other in catalyzing protein refolding. 26085184 5 32 theme highest 947:953 arg1 efficiency 955:964 highest efficiency 947:964 highest efficiency in the presence of both soluble form of AoCNX and TigA 947:1019 Denatured G1M9GN2-RNase was refolded with highest efficiency in the presence of both soluble form of AoCNX and TigA. 26085184 0 33 theme TigA 33:36 arg1 role 12:15 Cooperative role 0:15 Cooperative role of calnexin and TigA in Aspergillus oryzae glycoprotein folding. 0:80 Cooperative role of calnexin and TigA in Aspergillus oryzae glycoprotein folding. 26085184 1 34 theme ERp57 270:274 arg1 assistance 256:265 the assistance 252:265 the assistance of ERp57 in mammalian cells 252:293 Calnexin (CNX), known as a lectin chaperone located in the endoplasmic reticulum (ER), specifically recognizes G1M9GN2-proteins and facilitates their proper folding with the assistance of ERp57 in mammalian cells. 26085184 7 35 theme AoCNX 1382:1386 arg1 protein 1371:1377 a partner protein 1361:1377 a partner protein of AoCNX 1361:1386 The results suggested that in glycoprotein folding process of A. oryzae, TigA plays a similar role as ERp57 in mammalian cells, as a partner protein of AoCNX. 26085184 7 35 theme AoCNX 1382:1386 arg1 role 1324:1327 a similar role 1314:1327 a similar role 1314:1327 The results suggested that in glycoprotein folding process of A. oryzae, TigA plays a similar role as ERp57 in mammalian cells, as a partner protein of AoCNX. 26085184 4 36 theme refolding 735:743 arg1 experiments 745:755 refolding experiments 735:755 refolding experiments 735:755 For refolding experiments, a homogeneous monoglucosylated high-mannose-type glycoprotein G1M9GN2-RNase was chemoenzymatically synthesized from G1M9GN-oxazoline and GN-RNase. 26085184 7 37 theme A. 1292:1293 arg1 process 1281:1287 glycoprotein folding process 1260:1287 glycoprotein folding process of A. oryzae 1260:1300 The results suggested that in glycoprotein folding process of A. oryzae, TigA plays a similar role as ERp57 in mammalian cells, as a partner protein of AoCNX. 26085184 3 38 dep A. 523:524 arg1 oryzae 526:531 oryzae 526:531 oryzae 526:531 In this study, we found that a protein disulfide isomerase homolog TigA can bind with A. oryzae CNX (AoCNX), which was revealed to specifically recognize monoglucosylated glycans, similarly to CNX derived from other species, and accelerate the folding of G1M9GN2-ribonuclease (RNase) in vitro. 26085184 2 39 theme filamentous 383:393 arg1 fungus 395:400 a filamentous fungus 381:400 a filamentous fungus widely exploited in biotechnology 381:434 However, it has been left unidentified how CNX works in Aspergillus oryzae, which is a filamentous fungus widely exploited in biotechnology. 26085184 2 39 theme filamentous 383:393 arg1 oryzae 364:369 Aspergillus oryzae 352:369 Aspergillus oryzae 352:369 However, it has been left unidentified how CNX works in Aspergillus oryzae, which is a filamentous fungus widely exploited in biotechnology. 26085184 1 40 with folding 239:245 arg1 assistance 256:265 the assistance 252:265 the assistance of ERp57 in mammalian cells 252:293 Calnexin (CNX), known as a lectin chaperone located in the endoplasmic reticulum (ER), specifically recognizes G1M9GN2-proteins and facilitates their proper folding with the assistance of ERp57 in mammalian cells. 26085184 7 41 theme glycoprotein 1260:1271 arg1 process 1281:1287 glycoprotein folding process 1260:1287 glycoprotein folding process of A. oryzae 1260:1300 The results suggested that in glycoprotein folding process of A. oryzae, TigA plays a similar role as ERp57 in mammalian cells, as a partner protein of AoCNX. 26085184 0 42 theme Aspergillus 41:51 arg1 folding 73:79 Aspergillus oryzae glycoprotein folding 41:79 Aspergillus oryzae glycoprotein folding 41:79 Cooperative role of calnexin and TigA in Aspergillus oryzae glycoprotein folding. 26085184 1 43 theme mammalian 279:287 arg1 cells 289:293 mammalian cells 279:293 mammalian cells 279:293 Calnexin (CNX), known as a lectin chaperone located in the endoplasmic reticulum (ER), specifically recognizes G1M9GN2-proteins and facilitates their proper folding with the assistance of ERp57 in mammalian cells. 26085184 3 44 theme A. 523:524 arg1 CNX 533:535 A. oryzae CNX 523:535 A. oryzae CNX (AoCNX) 523:543 In this study, we found that a protein disulfide isomerase homolog TigA can bind with A. oryzae CNX (AoCNX), which was revealed to specifically recognize monoglucosylated glycans, similarly to CNX derived from other species, and accelerate the folding of G1M9GN2-ribonuclease (RNase) in vitro. 26085184 3 44 theme A. 523:524 arg1 AoCNX 538:542 AoCNX 538:542 AoCNX 538:542 In this study, we found that a protein disulfide isomerase homolog TigA can bind with A. oryzae CNX (AoCNX), which was revealed to specifically recognize monoglucosylated glycans, similarly to CNX derived from other species, and accelerate the folding of G1M9GN2-ribonuclease (RNase) in vitro. 26085184 4 45 theme monoglucosylated 772:787 arg1 G1M9GN2-RNase 820:832 a homogeneous monoglucosylated high-mannose-type glycoprotein G1M9GN2-RNase 758:832 a homogeneous monoglucosylated high-mannose-type glycoprotein G1M9GN2-RNase 758:832 For refolding experiments, a homogeneous monoglucosylated high-mannose-type glycoprotein G1M9GN2-RNase was chemoenzymatically synthesized from G1M9GN-oxazoline and GN-RNase. 26085184 5 46 theme TigA 1016:1019 arg1 form 998:1001 both soluble form 985:1001 both soluble form of AoCNX and TigA 985:1019 Denatured G1M9GN2-RNase was refolded with highest efficiency in the presence of both soluble form of AoCNX and TigA. 26085184 3 47 theme G1M9GN2-ribonuclease 692:711 arg1 folding 681:687 the folding 677:687 the folding of G1M9GN2-ribonuclease (RNase) 677:719 In this study, we found that a protein disulfide isomerase homolog TigA can bind with A. oryzae CNX (AoCNX), which was revealed to specifically recognize monoglucosylated glycans, similarly to CNX derived from other species, and accelerate the folding of G1M9GN2-ribonuclease (RNase) in vitro. 26085184 5 48 theme AoCNX 1006:1010 arg1 form 998:1001 both soluble form 985:1001 both soluble form of AoCNX and TigA 985:1019 Denatured G1M9GN2-RNase was refolded with highest efficiency in the presence of both soluble form of AoCNX and TigA. 26085184 5 49 theme Denatured 905:913 arg1 G1M9GN2-RNase 915:927 Denatured G1M9GN2-RNase 905:927 Denatured G1M9GN2-RNase 905:927 Denatured G1M9GN2-RNase was refolded with highest efficiency in the presence of both soluble form of AoCNX and TigA. 26085184 7 50 theme partner 1363:1369 arg1 protein 1371:1377 a partner protein 1361:1377 a partner protein of AoCNX 1361:1386 The results suggested that in glycoprotein folding process of A. oryzae, TigA plays a similar role as ERp57 in mammalian cells, as a partner protein of AoCNX. 26085184 7 50 theme partner 1363:1369 arg1 role 1324:1327 a similar role 1314:1327 a similar role 1314:1327 The results suggested that in glycoprotein folding process of A. oryzae, TigA plays a similar role as ERp57 in mammalian cells, as a partner protein of AoCNX. 26085184 7 51 theme similar 1316:1322 arg1 protein 1371:1377 a partner protein 1361:1377 a partner protein of AoCNX 1361:1386 The results suggested that in glycoprotein folding process of A. oryzae, TigA plays a similar role as ERp57 in mammalian cells, as a partner protein of AoCNX. 26085184 7 51 theme similar 1316:1322 arg1 role 1324:1327 a similar role 1314:1327 a similar role 1314:1327 The results suggested that in glycoprotein folding process of A. oryzae, TigA plays a similar role as ERp57 in mammalian cells, as a partner protein of AoCNX. 26085184 1 52 from reticulum 153:161 arg1 located 126:132 located 126:132 located 126:132 Calnexin (CNX), known as a lectin chaperone located in the endoplasmic reticulum (ER), specifically recognizes G1M9GN2-proteins and facilitates their proper folding with the assistance of ERp57 in mammalian cells. 26085184 0 53 theme glycoprotein 60:71 arg1 folding 73:79 Aspergillus oryzae glycoprotein folding 41:79 Aspergillus oryzae glycoprotein folding 41:79 Cooperative role of calnexin and TigA in Aspergillus oryzae glycoprotein folding. 26085184 3 54 theme monoglucosylated 591:606 arg1 glycans 608:614 monoglucosylated glycans 591:614 monoglucosylated glycans 591:614 In this study, we found that a protein disulfide isomerase homolog TigA can bind with A. oryzae CNX (AoCNX), which was revealed to specifically recognize monoglucosylated glycans, similarly to CNX derived from other species, and accelerate the folding of G1M9GN2-ribonuclease (RNase) in vitro. 26085184 5 55 theme soluble 990:996 arg1 form 998:1001 both soluble form 985:1001 both soluble form of AoCNX and TigA 985:1019 Denatured G1M9GN2-RNase was refolded with highest efficiency in the presence of both soluble form of AoCNX and TigA. 26085184 1 56 theme lectin 109:114 arg1 chaperone 116:124 a lectin chaperone 107:124 a lectin chaperone located in the endoplasmic reticulum (ER) 107:166 Calnexin (CNX), known as a lectin chaperone located in the endoplasmic reticulum (ER), specifically recognizes G1M9GN2-proteins and facilitates their proper folding with the assistance of ERp57 in mammalian cells. 26085184 0 57 theme oryzae 53:58 arg1 folding 73:79 Aspergillus oryzae glycoprotein folding 41:79 Aspergillus oryzae glycoprotein folding 41:79 Cooperative role of calnexin and TigA in Aspergillus oryzae glycoprotein folding. 26085184 7 58 dep A. 1292:1293 arg1 oryzae 1295:1300 A. oryzae 1292:1300 A. oryzae 1292:1300 The results suggested that in glycoprotein folding process of A. oryzae, TigA plays a similar role as ERp57 in mammalian cells, as a partner protein of AoCNX. 26085184 5 59 theme form 998:1001 arg1 presence 973:980 the presence 969:980 the presence of both soluble form of AoCNX and TigA 969:1019 Denatured G1M9GN2-RNase was refolded with highest efficiency in the presence of both soluble form of AoCNX and TigA. 26085184 6 60 theme mutation 1077:1084 arg1 analysis 1086:1093 mutation analysis 1077:1093 mutation analysis 1077:1093 TigA contains two thioredoxin domains with CGHC motif, mutation analysis of which revealed that the one in N-terminal regions is involved in binding to AoCNX, while the other in catalyzing protein refolding. 28077594 1 0 theme mucosal 177:183 arg1 pathogen 197:204 a mucosal respiratory pathogen 175:204 a mucosal respiratory pathogen causing contagious porcine pleuropneumonia 175:247 Actinobacillus pleuropneumoniae is a mucosal respiratory pathogen causing contagious porcine pleuropneumonia. 28077594 1 0 theme mucosal 177:183 arg1 pleuropneumoniae 155:170 Actinobacillus pleuropneumoniae 140:170 Actinobacillus pleuropneumoniae 140:170 Actinobacillus pleuropneumoniae is a mucosal respiratory pathogen causing contagious porcine pleuropneumonia. 28077594 7 1 theme deletion 1105:1112 arg1 mutants 1114:1120 deletion mutants 1105:1120 deletion mutants 1105:1120 We demonstrated the importance of NGT in virulence, by creating deletion mutants and testing them in a novel respiratory cell line adhesion model. 28077594 5 2 theme hexose 847:852 arg1 polymer 854:860 a hexose polymer 845:860 a hexose polymer that reacted with an anti-dextran antibody 845:903 From this information we used the A. pleuropneumoniae glycosylation locus to decorate an acceptor protein, within Escherichia coli, with a hexose polymer that reacted with an anti-dextran antibody. 28077594 7 3 theme adhesion 1172:1179 arg1 model 1181:1185 a novel respiratory cell line adhesion model 1142:1185 a novel respiratory cell line adhesion model 1142:1185 We demonstrated the importance of NGT in virulence, by creating deletion mutants and testing them in a novel respiratory cell line adhesion model. 28077594 1 4 theme respiratory 185:195 arg1 pathogen 197:204 a mucosal respiratory pathogen 175:204 a mucosal respiratory pathogen causing contagious porcine pleuropneumonia 175:247 Actinobacillus pleuropneumoniae is a mucosal respiratory pathogen causing contagious porcine pleuropneumonia. 28077594 1 4 theme respiratory 185:195 arg1 pleuropneumoniae 155:170 Actinobacillus pleuropneumoniae 140:170 Actinobacillus pleuropneumoniae 140:170 Actinobacillus pleuropneumoniae is a mucosal respiratory pathogen causing contagious porcine pleuropneumonia. 28077594 0 5 theme potential 105:113 arg1 use 115:117 potential use 105:117 potential use in glycoengineering 105:137 The N-linking glycosylation system from Actinobacillus pleuropneumoniae is required for adhesion and has potential use in glycoengineering. 28077594 7 6 theme line 1167:1170 arg1 model 1181:1185 a novel respiratory cell line adhesion model 1142:1185 a novel respiratory cell line adhesion model 1142:1185 We demonstrated the importance of NGT in virulence, by creating deletion mutants and testing them in a novel respiratory cell line adhesion model. 28077594 2 7 theme outer 333:337 arg1 proteins 348:355 outer membrane proteins 333:355 outer membrane proteins 333:355 Pathogenesis studies have demonstrated a major role for the capsule, exotoxins and outer membrane proteins. 28077594 6 8 dep 29 998:999 arg1 to 995:996 to 995:996 to 995:996 Mass spectrometry analysis of a truncated protein revealed that this operon could add up to 29 repeat units to the appropriate sequon. 28077594 5 9 theme A. 742:743 arg1 locus 776:780 the A. pleuropneumoniae glycosylation locus 738:780 the A. pleuropneumoniae glycosylation locus 738:780 From this information we used the A. pleuropneumoniae glycosylation locus to decorate an acceptor protein, within Escherichia coli, with a hexose polymer that reacted with an anti-dextran antibody. 28077594 5 10 used used 733:736 arg2 we 730:731 we 730:731 we 730:731 From this information we used the A. pleuropneumoniae glycosylation locus to decorate an acceptor protein, within Escherichia coli, with a hexose polymer that reacted with an anti-dextran antibody. 28077594 0 11 from pleuropneumoniae 55:70 arg1 system 28:33 The N-linking glycosylation system 0:33 The N-linking glycosylation system from Actinobacillus pleuropneumoniae 0:70 The N-linking glycosylation system from Actinobacillus pleuropneumoniae is required for adhesion and has potential use in glycoengineering. 28077594 7 12 theme respiratory 1150:1160 arg1 model 1181:1185 a novel respiratory cell line adhesion model 1142:1185 a novel respiratory cell line adhesion model 1142:1185 We demonstrated the importance of NGT in virulence, by creating deletion mutants and testing them in a novel respiratory cell line adhesion model. 28077594 7 13 from importance 1061:1070 arg1 virulence 1082:1090 virulence 1082:1090 virulence 1082:1090 We demonstrated the importance of NGT in virulence, by creating deletion mutants and testing them in a novel respiratory cell line adhesion model. 28077594 3 14 gly glycosylating 450:462 arg0 enzyme 464:469 a cytoplasmic N-linked glycosylating enzyme 427:469 a cytoplasmic N-linked glycosylating enzyme designated NGT 427:484 Actinobacillus pleuropneumoniae can also glycosylate proteins, using a cytoplasmic N-linked glycosylating enzyme designated NGT, but its transcriptional arrangement and role in virulence remains unknown. 28077594 5 15 dep A. 742:743 arg1 pleuropneumoniae 745:760 pleuropneumoniae 745:760 pleuropneumoniae 745:760 From this information we used the A. pleuropneumoniae glycosylation locus to decorate an acceptor protein, within Escherichia coli, with a hexose polymer that reacted with an anti-dextran antibody. 28077594 8 16 theme NGT 1234:1236 arg1 system 1252:1257 the NGT glycosylation system 1230:1257 the NGT glycosylation system 1230:1257 This study demonstrates the importance of the NGT glycosylation system for pathogenesis and its potential biotechnological application for glycoengineering. 28077594 0 17 theme N-linking 4:12 arg1 system 28:33 The N-linking glycosylation system 0:33 The N-linking glycosylation system from Actinobacillus pleuropneumoniae 0:70 The N-linking glycosylation system from Actinobacillus pleuropneumoniae is required for adhesion and has potential use in glycoengineering. 28077594 8 18 theme glycosylation 1238:1250 arg1 system 1252:1257 the NGT glycosylation system 1230:1257 the NGT glycosylation system 1230:1257 This study demonstrates the importance of the NGT glycosylation system for pathogenesis and its potential biotechnological application for glycoengineering. 28077594 5 19 theme glycosylation 762:774 arg1 locus 776:780 the A. pleuropneumoniae glycosylation locus 738:780 the A. pleuropneumoniae glycosylation locus 738:780 From this information we used the A. pleuropneumoniae glycosylation locus to decorate an acceptor protein, within Escherichia coli, with a hexose polymer that reacted with an anti-dextran antibody. 28077594 1 20 theme contagious 214:223 arg1 pleuropneumonia 233:247 contagious porcine pleuropneumonia 214:247 contagious porcine pleuropneumonia 214:247 Actinobacillus pleuropneumoniae is a mucosal respiratory pathogen causing contagious porcine pleuropneumonia. 28077594 5 21 theme anti-dextran 883:894 arg1 antibody 896:903 an anti-dextran antibody 880:903 an anti-dextran antibody 880:903 From this information we used the A. pleuropneumoniae glycosylation locus to decorate an acceptor protein, within Escherichia coli, with a hexose polymer that reacted with an anti-dextran antibody. 28077594 7 22 theme novel 1144:1148 arg1 model 1181:1185 a novel respiratory cell line adhesion model 1142:1185 a novel respiratory cell line adhesion model 1142:1185 We demonstrated the importance of NGT in virulence, by creating deletion mutants and testing them in a novel respiratory cell line adhesion model. 28077594 3 23 theme transcriptional 495:509 arg1 arrangement 511:521 its transcriptional arrangement 491:521 its transcriptional arrangement 491:521 Actinobacillus pleuropneumoniae can also glycosylate proteins, using a cytoplasmic N-linked glycosylating enzyme designated NGT, but its transcriptional arrangement and role in virulence remains unknown. 28077594 3 24 theme cytoplasmic 429:439 arg1 enzyme 464:469 a cytoplasmic N-linked glycosylating enzyme 427:469 a cytoplasmic N-linked glycosylating enzyme designated NGT 427:484 Actinobacillus pleuropneumoniae can also glycosylate proteins, using a cytoplasmic N-linked glycosylating enzyme designated NGT, but its transcriptional arrangement and role in virulence remains unknown. 28077594 4 25 theme transcriptional 627:641 arg1 unit 643:646 the putative transcriptional unit 614:646 the putative transcriptional unit 614:646 We investigated the NGT locus and demonstrated that the putative transcriptional unit consists of rimO, ngt and a glycosyltransferase termed agt. 28077594 7 26 theme cell 1162:1165 arg1 model 1181:1185 a novel respiratory cell line adhesion model 1142:1185 a novel respiratory cell line adhesion model 1142:1185 We demonstrated the importance of NGT in virulence, by creating deletion mutants and testing them in a novel respiratory cell line adhesion model. 28077594 3 27 theme N-linked 441:448 arg1 enzyme 464:469 a cytoplasmic N-linked glycosylating enzyme 427:469 a cytoplasmic N-linked glycosylating enzyme designated NGT 427:484 Actinobacillus pleuropneumoniae can also glycosylate proteins, using a cytoplasmic N-linked glycosylating enzyme designated NGT, but its transcriptional arrangement and role in virulence remains unknown. 28077594 7 28 theme NGT 1075:1077 arg1 importance 1061:1070 the importance 1057:1070 the importance of NGT in virulence 1057:1090 We demonstrated the importance of NGT in virulence, by creating deletion mutants and testing them in a novel respiratory cell line adhesion model. 28077594 2 29 theme membrane 339:346 arg1 proteins 348:355 outer membrane proteins 333:355 outer membrane proteins 333:355 Pathogenesis studies have demonstrated a major role for the capsule, exotoxins and outer membrane proteins. 28077594 0 30 theme Actinobacillus 40:53 arg1 pleuropneumoniae 55:70 Actinobacillus pleuropneumoniae 40:70 Actinobacillus pleuropneumoniae 40:70 The N-linking glycosylation system from Actinobacillus pleuropneumoniae is required for adhesion and has potential use in glycoengineering. 28077594 6 31 theme appropriate 1021:1031 arg1 sequon 1033:1038 the appropriate sequon 1017:1038 the appropriate sequon 1017:1038 Mass spectrometry analysis of a truncated protein revealed that this operon could add up to 29 repeat units to the appropriate sequon. 28077594 5 32 theme acceptor 797:804 arg1 protein 806:812 an acceptor protein 794:812 an acceptor protein 794:812 From this information we used the A. pleuropneumoniae glycosylation locus to decorate an acceptor protein, within Escherichia coli, with a hexose polymer that reacted with an anti-dextran antibody. 28077594 6 33 theme protein 948:954 arg1 analysis 924:931 Mass spectrometry analysis 906:931 Mass spectrometry analysis of a truncated protein 906:954 Mass spectrometry analysis of a truncated protein revealed that this operon could add up to 29 repeat units to the appropriate sequon. 28077594 2 34 theme major 291:295 arg1 role 297:300 a major role 289:300 a major role for the capsule, exotoxins and outer membrane proteins 289:355 Pathogenesis studies have demonstrated a major role for the capsule, exotoxins and outer membrane proteins. 28077594 1 35 theme porcine 225:231 arg1 pleuropneumonia 233:247 contagious porcine pleuropneumonia 214:247 contagious porcine pleuropneumonia 214:247 Actinobacillus pleuropneumoniae is a mucosal respiratory pathogen causing contagious porcine pleuropneumonia. 28077594 6 36 theme truncated 938:946 arg1 protein 948:954 a truncated protein 936:954 a truncated protein 936:954 Mass spectrometry analysis of a truncated protein revealed that this operon could add up to 29 repeat units to the appropriate sequon. 28077594 3 37 from role 527:530 arg1 virulence 535:543 virulence 535:543 virulence 535:543 Actinobacillus pleuropneumoniae can also glycosylate proteins, using a cytoplasmic N-linked glycosylating enzyme designated NGT, but its transcriptional arrangement and role in virulence remains unknown. 28077594 8 38 theme system 1252:1257 arg1 importance 1216:1225 the importance 1212:1225 the importance of the NGT glycosylation system for pathogenesis and its potential biotechnological application for glycoengineering 1212:1342 This study demonstrates the importance of the NGT glycosylation system for pathogenesis and its potential biotechnological application for glycoengineering. 28077594 8 39 theme biotechnological 1294:1309 arg1 application 1311:1321 its potential biotechnological application 1280:1321 its potential biotechnological application for glycoengineering 1280:1342 This study demonstrates the importance of the NGT glycosylation system for pathogenesis and its potential biotechnological application for glycoengineering. 28077594 3 40 gly glycosylate 399:409 arg1 proteins 411:418 proteins 411:418 proteins 411:418 Actinobacillus pleuropneumoniae can also glycosylate proteins, using a cytoplasmic N-linked glycosylating enzyme designated NGT, but its transcriptional arrangement and role in virulence remains unknown. 28077594 8 41 theme potential 1284:1292 arg1 application 1311:1321 its potential biotechnological application 1280:1321 its potential biotechnological application for glycoengineering 1280:1342 This study demonstrates the importance of the NGT glycosylation system for pathogenesis and its potential biotechnological application for glycoengineering. 28077594 4 42 theme putative 618:625 arg1 unit 643:646 the putative transcriptional unit 614:646 the putative transcriptional unit 614:646 We investigated the NGT locus and demonstrated that the putative transcriptional unit consists of rimO, ngt and a glycosyltransferase termed agt. 28077594 3 43 theme Actinobacillus 358:371 arg1 pleuropneumoniae 373:388 Actinobacillus pleuropneumoniae 358:388 Actinobacillus pleuropneumoniae 358:388 Actinobacillus pleuropneumoniae can also glycosylate proteins, using a cytoplasmic N-linked glycosylating enzyme designated NGT, but its transcriptional arrangement and role in virulence remains unknown. 28077594 2 44 theme Pathogenesis 250:261 arg1 studies 263:269 Pathogenesis studies 250:269 Pathogenesis studies 250:269 Pathogenesis studies have demonstrated a major role for the capsule, exotoxins and outer membrane proteins. 28077594 0 45 contain has 101:103 arg1 system 28:33 The N-linking glycosylation system 0:33 The N-linking glycosylation system from Actinobacillus pleuropneumoniae 0:70 The N-linking glycosylation system from Actinobacillus pleuropneumoniae is required for adhesion and has potential use in glycoengineering. 28077594 0 45 contain has 101:103 arg2 use 115:117 potential use 105:117 potential use in glycoengineering 105:137 The N-linking glycosylation system from Actinobacillus pleuropneumoniae is required for adhesion and has potential use in glycoengineering. 28077594 6 46 theme repeat 1001:1006 arg1 units 1008:1012 up to 29 repeat units 992:1012 up to 29 repeat units 992:1012 Mass spectrometry analysis of a truncated protein revealed that this operon could add up to 29 repeat units to the appropriate sequon. 28077594 0 47 from use 115:117 arg1 glycoengineering 122:137 glycoengineering 122:137 glycoengineering 122:137 The N-linking glycosylation system from Actinobacillus pleuropneumoniae is required for adhesion and has potential use in glycoengineering. 28077594 1 48 theme Actinobacillus 140:153 arg1 pathogen 197:204 a mucosal respiratory pathogen 175:204 a mucosal respiratory pathogen causing contagious porcine pleuropneumonia 175:247 Actinobacillus pleuropneumoniae is a mucosal respiratory pathogen causing contagious porcine pleuropneumonia. 28077594 1 48 theme Actinobacillus 140:153 arg1 pleuropneumoniae 155:170 Actinobacillus pleuropneumoniae 140:170 Actinobacillus pleuropneumoniae 140:170 Actinobacillus pleuropneumoniae is a mucosal respiratory pathogen causing contagious porcine pleuropneumonia. 28077594 6 49 theme spectrometry 911:922 arg1 analysis 924:931 Mass spectrometry analysis 906:931 Mass spectrometry analysis of a truncated protein 906:954 Mass spectrometry analysis of a truncated protein revealed that this operon could add up to 29 repeat units to the appropriate sequon. 28077594 3 50 link N-linked 441:448 arg1 enzyme 464:469 a cytoplasmic N-linked glycosylating enzyme 427:469 a cytoplasmic N-linked glycosylating enzyme designated NGT 427:484 Actinobacillus pleuropneumoniae can also glycosylate proteins, using a cytoplasmic N-linked glycosylating enzyme designated NGT, but its transcriptional arrangement and role in virulence remains unknown. 28077594 6 51 theme Mass 906:909 arg1 analysis 924:931 Mass spectrometry analysis 906:931 Mass spectrometry analysis of a truncated protein 906:954 Mass spectrometry analysis of a truncated protein revealed that this operon could add up to 29 repeat units to the appropriate sequon. 28077594 4 52 theme NGT 582:584 arg1 locus 586:590 the NGT locus 578:590 the NGT locus 578:590 We investigated the NGT locus and demonstrated that the putative transcriptional unit consists of rimO, ngt and a glycosyltransferase termed agt. 28077594 0 53 theme glycosylation 14:26 arg1 system 28:33 The N-linking glycosylation system 0:33 The N-linking glycosylation system from Actinobacillus pleuropneumoniae 0:70 The N-linking glycosylation system from Actinobacillus pleuropneumoniae is required for adhesion and has potential use in glycoengineering. 28077594 3 54 from arrangement 511:521 arg1 virulence 535:543 virulence 535:543 virulence 535:543 Actinobacillus pleuropneumoniae can also glycosylate proteins, using a cytoplasmic N-linked glycosylating enzyme designated NGT, but its transcriptional arrangement and role in virulence remains unknown. 28077594 3 55 theme glycosylating 450:462 arg1 enzyme 464:469 a cytoplasmic N-linked glycosylating enzyme 427:469 a cytoplasmic N-linked glycosylating enzyme designated NGT 427:484 Actinobacillus pleuropneumoniae can also glycosylate proteins, using a cytoplasmic N-linked glycosylating enzyme designated NGT, but its transcriptional arrangement and role in virulence remains unknown. 25119505 7 0 theme stages 1653:1658 arg1 system 1633:1638 an in vitro model system 1615:1638 an in vitro model system of these two stages of composite stone formation to study the role that various acidic macromolecules may play 1615:1749 Therefore, our goal is to develop an in vitro model system of these two stages of composite stone formation to study the role that various acidic macromolecules may play. 25119505 9 1 theme tissue 1934:1939 arg1 MatriStem 1954:1962 MatriStem 1954:1962 MatriStem 1954:1962 To mimic the tissue environment, MatriStem(®) (ACell, Inc.), a decellularized porcine urinary bladder matrix was used, because it has both an intact epithelial basement membrane surface and a tunica propria layer, thus providing the two types of matrix constituents found associated with mineral in the early stages of RP formation. 25119505 9 1 theme tissue 1934:1939 arg1 environment 1941:1951 the tissue environment 1930:1951 the tissue environment 1930:1951 To mimic the tissue environment, MatriStem(®) (ACell, Inc.), a decellularized porcine urinary bladder matrix was used, because it has both an intact epithelial basement membrane surface and a tunica propria layer, thus providing the two types of matrix constituents found associated with mineral in the early stages of RP formation. 25119505 5 2 theme liquid 1297:1302 arg1 precursor 1320:1328 a liquid phase amorphous precursor 1295:1328 a liquid phase amorphous precursor to the mineral 1295:1343 Our group has found that many of the unusual morphologies found in RP and stones, such as concentrically laminated spherulites and mineralized collagenous tissue, can be reproduced in vitro using a polymer-induced liquid precursor (PILP) process, in which acidic polypeptides induce a liquid phase amorphous precursor to the mineral, yielding non-equilibrium crystal morphologies. 25119505 2 3 theme calcium 295:301 arg1 stones 317:322 calcium oxalate renal stones 295:322 calcium oxalate renal stones 295:322 This group forms calcium oxalate renal stones without any systemic symptoms, which contributes to the difficulty of understanding and treating this painful and recurring disease. 25119505 13 4 theme scaffolds 3018:3026 arg1 mineralization 2986:2999 mineralization 2986:2999 mineralization of native tissue scaffolds 2986:3026 We believe that mineralization of native tissue scaffolds is useful for developing a model system of stone formation, with the ultimate goal of developing strategies to avoid RP and its detrimental consequences in stone formation, or developing therapeutic treatments to prevent or cure the disease. 25119505 12 5 theme kidney 2822:2827 arg1 stones 2829:2834 kidney stones 2822:2834 kidney stones 2822:2834 Although these studies are only preliminary, they support our hypothesis that kidney stones may involve non-classical crystallization pathways induced by the large variety of macromolecular species in the urinary environment. 25119505 5 6 theme amorphous 1310:1318 arg1 precursor 1320:1328 a liquid phase amorphous precursor 1295:1328 a liquid phase amorphous precursor to the mineral 1295:1343 Our group has found that many of the unusual morphologies found in RP and stones, such as concentrically laminated spherulites and mineralized collagenous tissue, can be reproduced in vitro using a polymer-induced liquid precursor (PILP) process, in which acidic polypeptides induce a liquid phase amorphous precursor to the mineral, yielding non-equilibrium crystal morphologies. 25119505 1 7 theme kidney 214:219 arg1 formers 227:233 kidney stone formers 214:233 kidney stone formers 214:233 Randall's plaque (RP) deposits seem to be consistent among the most common type of kidney stone formers, idiopathic calcium oxalate stone formers. 25119505 4 8 theme Henle 770:774 arg1 loops 761:765 the thin loops 752:765 the thin loops of Henle, which then fuse and spread into the interstitial tissue, and ultimately make their way across the urothelium, where upon exposure to the urine, the mineralized tissue serves as a nidus for overgrowth with calcium oxalate into a stone 752:1009 One main theory of RP formation is that calcium phosphate deposits initially form in the basement membrane of the thin loops of Henle, which then fuse and spread into the interstitial tissue, and ultimately make their way across the urothelium, where upon exposure to the urine, the mineralized tissue serves as a nidus for overgrowth with calcium oxalate into a stone. 25119505 9 9 dep found 2187:2191 arg1 associated 2193:2202 associated 2193:2202 associated with mineral in the early stages of RP formation 2193:2251 To mimic the tissue environment, MatriStem(®) (ACell, Inc.), a decellularized porcine urinary bladder matrix was used, because it has both an intact epithelial basement membrane surface and a tunica propria layer, thus providing the two types of matrix constituents found associated with mineral in the early stages of RP formation. 25119505 9 9 dep found 2187:2191 arg1 constituents 2174:2185 matrix constituents 2167:2185 matrix constituents found associated with mineral in the early stages of RP formation 2167:2251 To mimic the tissue environment, MatriStem(®) (ACell, Inc.), a decellularized porcine urinary bladder matrix was used, because it has both an intact epithelial basement membrane surface and a tunica propria layer, thus providing the two types of matrix constituents found associated with mineral in the early stages of RP formation. 25119505 5 10 theme acidic 1268:1273 arg1 polypeptides 1275:1286 acidic polypeptides 1268:1286 acidic polypeptides 1268:1286 Our group has found that many of the unusual morphologies found in RP and stones, such as concentrically laminated spherulites and mineralized collagenous tissue, can be reproduced in vitro using a polymer-induced liquid precursor (PILP) process, in which acidic polypeptides induce a liquid phase amorphous precursor to the mineral, yielding non-equilibrium crystal morphologies. 25119505 6 11 theme many 1414:1417 arg1 proteins 1426:1433 many acidic proteins 1414:1433 many acidic proteins 1414:1433 Given that there are many acidic proteins and polysaccharides present in the renal tissue and urine, we have put forth the hypothesis that the PILP system may be involved in urolithiasis. 25119505 11 12 theme basement 2725:2732 arg1 membrane 2734:2741 the basement membrane 2721:2741 the basement membrane 2721:2741 The interstitium side predominantly consisted of collagen-associated mineral, while the luminal side had much less mineral, which appeared to be tiny spherules embedded within the basement membrane. 25119505 13 13 theme native 3004:3009 arg1 scaffolds 3018:3026 native tissue scaffolds 3004:3026 native tissue scaffolds 3004:3026 We believe that mineralization of native tissue scaffolds is useful for developing a model system of stone formation, with the ultimate goal of developing strategies to avoid RP and its detrimental consequences in stone formation, or developing therapeutic treatments to prevent or cure the disease. 25119505 12 14 from variety 2908:2914 arg1 environment 2957:2967 the urinary environment 2945:2967 the urinary environment 2945:2967 Although these studies are only preliminary, they support our hypothesis that kidney stones may involve non-classical crystallization pathways induced by the large variety of macromolecular species in the urinary environment. 25119505 0 15 theme biopolymers 88:98 arg1 role 73:76 the role 69:76 the role of acidic biopolymers in idiopathic stone formation 69:128 Biomimetic Randall's plaque as an in vitro model system for studying the role of acidic biopolymers in idiopathic stone formation. 25119505 3 16 theme system 500:505 arg1 development 467:477 the development 463:477 the development 463:477 Thus, the development of an in vitro model system to study idiopathic nephrolithiasis, beginning with RP pathogenesis, can help in identifying how plaques and subsequently stones form. 25119505 6 17 from urine 1487:1491 arg1 present 1455:1461 present 1455:1461 present 1455:1461 Given that there are many acidic proteins and polysaccharides present in the renal tissue and urine, we have put forth the hypothesis that the PILP system may be involved in urolithiasis. 25119505 10 18 theme PILP 2283:2286 arg1 process 2288:2294 the PILP process 2279:2294 the PILP process 2279:2294 We found that when using the PILP process to mineralize this tissue matrix, the two sides led to dramatically different mineral textures, and they bore a striking resemblance to native RP, which was not seen in the tissue mineralized via the classical crystal nucleation and growth process. 25119505 10 19 theme mineral 2374:2380 arg1 textures 2382:2389 dramatically different mineral textures 2351:2389 dramatically different mineral textures 2351:2389 We found that when using the PILP process to mineralize this tissue matrix, the two sides led to dramatically different mineral textures, and they bore a striking resemblance to native RP, which was not seen in the tissue mineralized via the classical crystal nucleation and growth process. 25119505 0 20 theme idiopathic 103:112 arg1 formation 120:128 idiopathic stone formation 103:128 idiopathic stone formation 103:128 Biomimetic Randall's plaque as an in vitro model system for studying the role of acidic biopolymers in idiopathic stone formation. 25119505 10 21 contain bore 2401:2404 arg1 they 2396:2399 they 2396:2399 they 2396:2399 We found that when using the PILP process to mineralize this tissue matrix, the two sides led to dramatically different mineral textures, and they bore a striking resemblance to native RP, which was not seen in the tissue mineralized via the classical crystal nucleation and growth process. 25119505 10 21 contain bore 2401:2404 arg2 resemblance 2417:2427 a striking resemblance 2406:2427 a striking resemblance to native RP, which was not seen in the tissue mineralized via the classical crystal nucleation and growth process 2406:2542 We found that when using the PILP process to mineralize this tissue matrix, the two sides led to dramatically different mineral textures, and they bore a striking resemblance to native RP, which was not seen in the tissue mineralized via the classical crystal nucleation and growth process. 25119505 5 22 theme unusual 1049:1055 arg1 morphologies 1057:1068 the unusual morphologies 1045:1068 the unusual morphologies found in RP and stones, such as concentrically laminated spherulites and mineralized collagenous tissue, 1045:1173 Our group has found that many of the unusual morphologies found in RP and stones, such as concentrically laminated spherulites and mineralized collagenous tissue, can be reproduced in vitro using a polymer-induced liquid precursor (PILP) process, in which acidic polypeptides induce a liquid phase amorphous precursor to the mineral, yielding non-equilibrium crystal morphologies. 25119505 14 23 theme NIDDK 3283:3287 arg1 RO1DK092311 3295:3305 NIDDK grant RO1DK092311 3283:3305 NIDDK grant RO1DK092311 3283:3305 Supported by NIDDK grant RO1DK092311. 25119505 6 24 theme renal 1470:1474 arg1 tissue 1476:1481 the renal tissue 1466:1481 the renal tissue 1466:1481 Given that there are many acidic proteins and polysaccharides present in the renal tissue and urine, we have put forth the hypothesis that the PILP system may be involved in urolithiasis. 25119505 6 25 theme PILP 1536:1539 arg1 system 1541:1546 the PILP system 1532:1546 the PILP system 1532:1546 Given that there are many acidic proteins and polysaccharides present in the renal tissue and urine, we have put forth the hypothesis that the PILP system may be involved in urolithiasis. 25119505 4 26 theme RP 661:662 arg1 formation 664:672 RP formation 661:672 RP formation 661:672 One main theory of RP formation is that calcium phosphate deposits initially form in the basement membrane of the thin loops of Henle, which then fuse and spread into the interstitial tissue, and ultimately make their way across the urothelium, where upon exposure to the urine, the mineralized tissue serves as a nidus for overgrowth with calcium oxalate into a stone. 25119505 9 27 theme decellularized 1984:1997 arg1 bladder 2015:2021 a decellularized porcine urinary bladder 1982:2021 a decellularized porcine urinary bladder matrix 1982:2028 To mimic the tissue environment, MatriStem(®) (ACell, Inc.), a decellularized porcine urinary bladder matrix was used, because it has both an intact epithelial basement membrane surface and a tunica propria layer, thus providing the two types of matrix constituents found associated with mineral in the early stages of RP formation. 25119505 6 28 from tissue 1476:1481 arg1 present 1455:1461 present 1455:1461 present 1455:1461 Given that there are many acidic proteins and polysaccharides present in the renal tissue and urine, we have put forth the hypothesis that the PILP system may be involved in urolithiasis. 25119505 10 29 theme tissue 2315:2320 arg1 matrix 2322:2327 this tissue matrix 2310:2327 this tissue matrix 2310:2327 We found that when using the PILP process to mineralize this tissue matrix, the two sides led to dramatically different mineral textures, and they bore a striking resemblance to native RP, which was not seen in the tissue mineralized via the classical crystal nucleation and growth process. 25119505 9 30 theme urinary 2007:2013 arg1 bladder 2015:2021 a decellularized porcine urinary bladder 1982:2021 a decellularized porcine urinary bladder matrix 1982:2028 To mimic the tissue environment, MatriStem(®) (ACell, Inc.), a decellularized porcine urinary bladder matrix was used, because it has both an intact epithelial basement membrane surface and a tunica propria layer, thus providing the two types of matrix constituents found associated with mineral in the early stages of RP formation. 25119505 0 31 theme model 43:47 arg1 system 49:54 an in vitro model system 31:54 an in vitro model system for studying the role of acidic biopolymers in idiopathic stone formation 31:128 Biomimetic Randall's plaque as an in vitro model system for studying the role of acidic biopolymers in idiopathic stone formation. 25119505 2 32 theme recurring 438:446 arg1 disease 448:454 this painful and recurring disease 421:454 this painful and recurring disease 421:454 This group forms calcium oxalate renal stones without any systemic symptoms, which contributes to the difficulty of understanding and treating this painful and recurring disease. 25119505 9 33 theme RP 2240:2241 arg1 formation 2243:2251 RP formation 2240:2251 RP formation 2240:2251 To mimic the tissue environment, MatriStem(®) (ACell, Inc.), a decellularized porcine urinary bladder matrix was used, because it has both an intact epithelial basement membrane surface and a tunica propria layer, thus providing the two types of matrix constituents found associated with mineral in the early stages of RP formation. 25119505 6 34 from present 1455:1461 arg1 urine 1487:1491 urine 1487:1491 urine 1487:1491 Given that there are many acidic proteins and polysaccharides present in the renal tissue and urine, we have put forth the hypothesis that the PILP system may be involved in urolithiasis. 25119505 6 34 from present 1455:1461 arg1 tissue 1476:1481 the renal tissue 1466:1481 the renal tissue 1466:1481 Given that there are many acidic proteins and polysaccharides present in the renal tissue and urine, we have put forth the hypothesis that the PILP system may be involved in urolithiasis. 25119505 13 35 from RP 3145:3146 arg1 formation 3190:3198 stone formation 3184:3198 stone formation 3184:3198 We believe that mineralization of native tissue scaffolds is useful for developing a model system of stone formation, with the ultimate goal of developing strategies to avoid RP and its detrimental consequences in stone formation, or developing therapeutic treatments to prevent or cure the disease. 25119505 5 36 theme crystal 1371:1377 arg1 morphologies 1379:1390 non-equilibrium crystal morphologies 1355:1390 non-equilibrium crystal morphologies 1355:1390 Our group has found that many of the unusual morphologies found in RP and stones, such as concentrically laminated spherulites and mineralized collagenous tissue, can be reproduced in vitro using a polymer-induced liquid precursor (PILP) process, in which acidic polypeptides induce a liquid phase amorphous precursor to the mineral, yielding non-equilibrium crystal morphologies. 25119505 5 37 theme mineralized 1143:1153 arg1 tissue 1167:1172 mineralized collagenous tissue 1143:1172 mineralized collagenous tissue 1143:1172 Our group has found that many of the unusual morphologies found in RP and stones, such as concentrically laminated spherulites and mineralized collagenous tissue, can be reproduced in vitro using a polymer-induced liquid precursor (PILP) process, in which acidic polypeptides induce a liquid phase amorphous precursor to the mineral, yielding non-equilibrium crystal morphologies. 25119505 8 38 theme biomimetic 1815:1824 arg1 " 1825:1825 "biomimetic" RP 1814:1828 "biomimetic" RP 1814:1828 In our initial experiments presented here, the development of "biomimetic" RP was investigated, which will then serve as a nidus for calcium oxalate overgrowth studies. 25119505 9 39 theme formation 2243:2251 arg1 stages 2230:2235 the early stages 2220:2235 the early stages of RP formation 2220:2251 To mimic the tissue environment, MatriStem(®) (ACell, Inc.), a decellularized porcine urinary bladder matrix was used, because it has both an intact epithelial basement membrane surface and a tunica propria layer, thus providing the two types of matrix constituents found associated with mineral in the early stages of RP formation. 25119505 11 40 theme interstitium 2549:2560 arg1 side 2562:2565 The interstitium side 2545:2565 The interstitium side 2545:2565 The interstitium side predominantly consisted of collagen-associated mineral, while the luminal side had much less mineral, which appeared to be tiny spherules embedded within the basement membrane. 25119505 11 41 theme embedded 2705:2712 arg1 spherules 2695:2703 tiny spherules 2690:2703 tiny spherules embedded within the basement membrane 2690:2741 The interstitium side predominantly consisted of collagen-associated mineral, while the luminal side had much less mineral, which appeared to be tiny spherules embedded within the basement membrane. 25119505 6 42 attach present 1455:1461 arg2 proteins 1426:1433 many acidic proteins 1414:1433 many acidic proteins 1414:1433 Given that there are many acidic proteins and polysaccharides present in the renal tissue and urine, we have put forth the hypothesis that the PILP system may be involved in urolithiasis. 25119505 6 42 attach present 1455:1461 arg1 urine 1487:1491 urine 1487:1491 urine 1487:1491 Given that there are many acidic proteins and polysaccharides present in the renal tissue and urine, we have put forth the hypothesis that the PILP system may be involved in urolithiasis. 25119505 6 42 attach present 1455:1461 arg1 tissue 1476:1481 the renal tissue 1466:1481 the renal tissue 1466:1481 Given that there are many acidic proteins and polysaccharides present in the renal tissue and urine, we have put forth the hypothesis that the PILP system may be involved in urolithiasis. 25119505 10 43 theme classical 2496:2504 arg1 nucleation 2514:2523 the classical crystal nucleation 2492:2523 the classical crystal nucleation 2492:2523 We found that when using the PILP process to mineralize this tissue matrix, the two sides led to dramatically different mineral textures, and they bore a striking resemblance to native RP, which was not seen in the tissue mineralized via the classical crystal nucleation and growth process. 25119505 5 44 theme liquid 1226:1231 arg1 process 1250:1256 a polymer-induced liquid precursor (PILP) process 1208:1256 a polymer-induced liquid precursor (PILP) process 1208:1256 Our group has found that many of the unusual morphologies found in RP and stones, such as concentrically laminated spherulites and mineralized collagenous tissue, can be reproduced in vitro using a polymer-induced liquid precursor (PILP) process, in which acidic polypeptides induce a liquid phase amorphous precursor to the mineral, yielding non-equilibrium crystal morphologies. 25119505 0 45 theme Biomimetic 0:9 arg1 plaque 21:26 Biomimetic Randall's plaque 0:26 Biomimetic Randall's plaque 0:26 Biomimetic Randall's plaque as an in vitro model system for studying the role of acidic biopolymers in idiopathic stone formation. 25119505 1 46 theme stone 221:225 arg1 formers 227:233 kidney stone formers 214:233 kidney stone formers 214:233 Randall's plaque (RP) deposits seem to be consistent among the most common type of kidney stone formers, idiopathic calcium oxalate stone formers. 25119505 11 47 theme tiny 2690:2693 arg1 spherules 2695:2703 tiny spherules 2690:2703 tiny spherules embedded within the basement membrane 2690:2741 The interstitium side predominantly consisted of collagen-associated mineral, while the luminal side had much less mineral, which appeared to be tiny spherules embedded within the basement membrane. 25119505 13 48 theme formation 3077:3085 arg1 system 3061:3066 a model system 3053:3066 a model system of stone formation 3053:3085 We believe that mineralization of native tissue scaffolds is useful for developing a model system of stone formation, with the ultimate goal of developing strategies to avoid RP and its detrimental consequences in stone formation, or developing therapeutic treatments to prevent or cure the disease. 25119505 8 49 theme calcium 1885:1891 arg1 studies 1912:1918 calcium oxalate overgrowth studies 1885:1918 calcium oxalate overgrowth studies 1885:1918 In our initial experiments presented here, the development of "biomimetic" RP was investigated, which will then serve as a nidus for calcium oxalate overgrowth studies. 25119505 4 50 theme calcium 682:688 arg1 deposits 700:707 calcium phosphate deposits 682:707 calcium phosphate deposits 682:707 One main theory of RP formation is that calcium phosphate deposits initially form in the basement membrane of the thin loops of Henle, which then fuse and spread into the interstitial tissue, and ultimately make their way across the urothelium, where upon exposure to the urine, the mineralized tissue serves as a nidus for overgrowth with calcium oxalate into a stone. 25119505 5 51 theme morphologies 1057:1068 arg1 many 1037:1040 many 1037:1040 many 1037:1040 Our group has found that many of the unusual morphologies found in RP and stones, such as concentrically laminated spherulites and mineralized collagenous tissue, can be reproduced in vitro using a polymer-induced liquid precursor (PILP) process, in which acidic polypeptides induce a liquid phase amorphous precursor to the mineral, yielding non-equilibrium crystal morphologies. 25119505 5 51 theme morphologies 1057:1068 arg1 morphologies 1057:1068 the unusual morphologies 1045:1068 the unusual morphologies found in RP and stones, such as concentrically laminated spherulites and mineralized collagenous tissue, 1045:1173 Our group has found that many of the unusual morphologies found in RP and stones, such as concentrically laminated spherulites and mineralized collagenous tissue, can be reproduced in vitro using a polymer-induced liquid precursor (PILP) process, in which acidic polypeptides induce a liquid phase amorphous precursor to the mineral, yielding non-equilibrium crystal morphologies. 25119505 13 52 theme stone 3071:3075 arg1 formation 3077:3085 stone formation 3071:3085 stone formation 3071:3085 We believe that mineralization of native tissue scaffolds is useful for developing a model system of stone formation, with the ultimate goal of developing strategies to avoid RP and its detrimental consequences in stone formation, or developing therapeutic treatments to prevent or cure the disease. 25119505 8 53 theme overgrowth 1901:1910 arg1 studies 1912:1918 calcium oxalate overgrowth studies 1885:1918 calcium oxalate overgrowth studies 1885:1918 In our initial experiments presented here, the development of "biomimetic" RP was investigated, which will then serve as a nidus for calcium oxalate overgrowth studies. 25119505 2 54 theme painful 426:432 arg1 disease 448:454 this painful and recurring disease 421:454 this painful and recurring disease 421:454 This group forms calcium oxalate renal stones without any systemic symptoms, which contributes to the difficulty of understanding and treating this painful and recurring disease. 25119505 9 55 from stages 2230:2235 arg1 mineral 2209:2215 mineral 2209:2215 mineral 2209:2215 To mimic the tissue environment, MatriStem(®) (ACell, Inc.), a decellularized porcine urinary bladder matrix was used, because it has both an intact epithelial basement membrane surface and a tunica propria layer, thus providing the two types of matrix constituents found associated with mineral in the early stages of RP formation. 25119505 9 56 theme epithelial 2070:2079 arg1 surface 2099:2105 an intact epithelial basement membrane surface 2060:2105 an intact epithelial basement membrane surface 2060:2105 To mimic the tissue environment, MatriStem(®) (ACell, Inc.), a decellularized porcine urinary bladder matrix was used, because it has both an intact epithelial basement membrane surface and a tunica propria layer, thus providing the two types of matrix constituents found associated with mineral in the early stages of RP formation. 25119505 1 57 theme calcium 247:253 arg1 formers 269:275 consistent among the most common type of kidney stone formers, idiopathic calcium oxalate stone formers 173:275 consistent among the most common type of kidney stone formers, idiopathic calcium oxalate stone formers 173:275 Randall's plaque (RP) deposits seem to be consistent among the most common type of kidney stone formers, idiopathic calcium oxalate stone formers. 25119505 0 58 dep in 34:35 arg1 vitro 37:41 vitro 37:41 vitro 37:41 Biomimetic Randall's plaque as an in vitro model system for studying the role of acidic biopolymers in idiopathic stone formation. 25119505 13 59 theme developing 3204:3213 arg1 treatments 3227:3236 developing therapeutic treatments 3204:3236 developing therapeutic treatments 3204:3236 We believe that mineralization of native tissue scaffolds is useful for developing a model system of stone formation, with the ultimate goal of developing strategies to avoid RP and its detrimental consequences in stone formation, or developing therapeutic treatments to prevent or cure the disease. 25119505 9 60 used used 2034:2037 arg2 matrix 2023:2028 a decellularized porcine urinary bladder matrix 1982:2028 a decellularized porcine urinary bladder matrix 1982:2028 To mimic the tissue environment, MatriStem(®) (ACell, Inc.), a decellularized porcine urinary bladder matrix was used, because it has both an intact epithelial basement membrane surface and a tunica propria layer, thus providing the two types of matrix constituents found associated with mineral in the early stages of RP formation. 25119505 4 61 theme loops 761:765 arg1 membrane 740:747 the basement membrane 727:747 the basement membrane of the thin loops of Henle, which then fuse and spread into the interstitial tissue, and ultimately make their way across the urothelium, where upon exposure to the urine, the mineralized tissue serves as a nidus for overgrowth with calcium oxalate into a stone 727:1009 One main theory of RP formation is that calcium phosphate deposits initially form in the basement membrane of the thin loops of Henle, which then fuse and spread into the interstitial tissue, and ultimately make their way across the urothelium, where upon exposure to the urine, the mineralized tissue serves as a nidus for overgrowth with calcium oxalate into a stone. 25119505 9 62 theme membrane 2090:2097 arg1 surface 2099:2105 an intact epithelial basement membrane surface 2060:2105 an intact epithelial basement membrane surface 2060:2105 To mimic the tissue environment, MatriStem(®) (ACell, Inc.), a decellularized porcine urinary bladder matrix was used, because it has both an intact epithelial basement membrane surface and a tunica propria layer, thus providing the two types of matrix constituents found associated with mineral in the early stages of RP formation. 25119505 0 63 theme in 34:35 arg1 system 49:54 an in vitro model system 31:54 an in vitro model system for studying the role of acidic biopolymers in idiopathic stone formation 31:128 Biomimetic Randall's plaque as an in vitro model system for studying the role of acidic biopolymers in idiopathic stone formation. 25119505 1 64 theme stone 263:267 arg1 formers 269:275 consistent among the most common type of kidney stone formers, idiopathic calcium oxalate stone formers 173:275 consistent among the most common type of kidney stone formers, idiopathic calcium oxalate stone formers 173:275 Randall's plaque (RP) deposits seem to be consistent among the most common type of kidney stone formers, idiopathic calcium oxalate stone formers. 25119505 7 65 theme various 1712:1718 arg1 macromolecules 1727:1740 various acidic macromolecules 1712:1740 various acidic macromolecules 1712:1740 Therefore, our goal is to develop an in vitro model system of these two stages of composite stone formation to study the role that various acidic macromolecules may play. 25119505 7 66 theme stone 1673:1677 arg1 formation 1679:1687 composite stone formation 1663:1687 composite stone formation 1663:1687 Therefore, our goal is to develop an in vitro model system of these two stages of composite stone formation to study the role that various acidic macromolecules may play. 25119505 10 67 theme growth 2529:2534 arg1 process 2536:2542 growth process 2529:2542 growth process 2529:2542 We found that when using the PILP process to mineralize this tissue matrix, the two sides led to dramatically different mineral textures, and they bore a striking resemblance to native RP, which was not seen in the tissue mineralized via the classical crystal nucleation and growth process. 25119505 1 68 theme consistent 173:182 arg1 formers 269:275 consistent among the most common type of kidney stone formers, idiopathic calcium oxalate stone formers 173:275 consistent among the most common type of kidney stone formers, idiopathic calcium oxalate stone formers 173:275 Randall's plaque (RP) deposits seem to be consistent among the most common type of kidney stone formers, idiopathic calcium oxalate stone formers. 25119505 4 69 theme calcium 982:988 arg1 oxalate 990:996 calcium oxalate 982:996 calcium oxalate into a stone 982:1009 One main theory of RP formation is that calcium phosphate deposits initially form in the basement membrane of the thin loops of Henle, which then fuse and spread into the interstitial tissue, and ultimately make their way across the urothelium, where upon exposure to the urine, the mineralized tissue serves as a nidus for overgrowth with calcium oxalate into a stone. 25119505 9 70 theme tunica 2113:2118 arg1 layer 2128:2132 a tunica propria layer 2111:2132 a tunica propria layer 2111:2132 To mimic the tissue environment, MatriStem(®) (ACell, Inc.), a decellularized porcine urinary bladder matrix was used, because it has both an intact epithelial basement membrane surface and a tunica propria layer, thus providing the two types of matrix constituents found associated with mineral in the early stages of RP formation. 25119505 12 71 from species 2934:2940 arg1 environment 2957:2967 the urinary environment 2945:2967 the urinary environment 2945:2967 Although these studies are only preliminary, they support our hypothesis that kidney stones may involve non-classical crystallization pathways induced by the large variety of macromolecular species in the urinary environment. 25119505 2 72 theme oxalate 303:309 arg1 stones 317:322 calcium oxalate renal stones 295:322 calcium oxalate renal stones 295:322 This group forms calcium oxalate renal stones without any systemic symptoms, which contributes to the difficulty of understanding and treating this painful and recurring disease. 25119505 1 73 theme common 199:204 arg1 type 206:209 the most common type 190:209 the most common type of kidney stone formers 190:233 Randall's plaque (RP) deposits seem to be consistent among the most common type of kidney stone formers, idiopathic calcium oxalate stone formers. 25119505 9 74 contain has 2051:2053 arg2 layer 2128:2132 a tunica propria layer 2111:2132 a tunica propria layer 2111:2132 To mimic the tissue environment, MatriStem(®) (ACell, Inc.), a decellularized porcine urinary bladder matrix was used, because it has both an intact epithelial basement membrane surface and a tunica propria layer, thus providing the two types of matrix constituents found associated with mineral in the early stages of RP formation. 25119505 9 74 contain has 2051:2053 arg1 it 2048:2049 it 2048:2049 it 2048:2049 To mimic the tissue environment, MatriStem(®) (ACell, Inc.), a decellularized porcine urinary bladder matrix was used, because it has both an intact epithelial basement membrane surface and a tunica propria layer, thus providing the two types of matrix constituents found associated with mineral in the early stages of RP formation. 25119505 9 74 contain has 2051:2053 arg2 surface 2099:2105 an intact epithelial basement membrane surface 2060:2105 an intact epithelial basement membrane surface 2060:2105 To mimic the tissue environment, MatriStem(®) (ACell, Inc.), a decellularized porcine urinary bladder matrix was used, because it has both an intact epithelial basement membrane surface and a tunica propria layer, thus providing the two types of matrix constituents found associated with mineral in the early stages of RP formation. 25119505 12 75 theme macromolecular 2919:2932 arg1 species 2934:2940 macromolecular species 2919:2940 macromolecular species in the urinary environment 2919:2967 Although these studies are only preliminary, they support our hypothesis that kidney stones may involve non-classical crystallization pathways induced by the large variety of macromolecular species in the urinary environment. 25119505 7 76 dep in 1618:1619 arg1 vitro 1621:1625 vitro 1621:1625 vitro 1621:1625 Therefore, our goal is to develop an in vitro model system of these two stages of composite stone formation to study the role that various acidic macromolecules may play. 25119505 12 77 theme crystallization 2862:2876 arg1 pathways 2878:2885 non-classical crystallization pathways 2848:2885 non-classical crystallization pathways induced by the large variety of macromolecular species in the urinary environment 2848:2967 Although these studies are only preliminary, they support our hypothesis that kidney stones may involve non-classical crystallization pathways induced by the large variety of macromolecular species in the urinary environment. 25119505 5 78 theme phase 1304:1308 arg1 precursor 1320:1328 a liquid phase amorphous precursor 1295:1328 a liquid phase amorphous precursor to the mineral 1295:1343 Our group has found that many of the unusual morphologies found in RP and stones, such as concentrically laminated spherulites and mineralized collagenous tissue, can be reproduced in vitro using a polymer-induced liquid precursor (PILP) process, in which acidic polypeptides induce a liquid phase amorphous precursor to the mineral, yielding non-equilibrium crystal morphologies. 25119505 3 79 theme in 485:486 arg1 system 500:505 an in vitro model system 482:505 an in vitro model system to study idiopathic nephrolithiasis 482:541 Thus, the development of an in vitro model system to study idiopathic nephrolithiasis, beginning with RP pathogenesis, can help in identifying how plaques and subsequently stones form. 25119505 7 80 theme model 1627:1631 arg1 system 1633:1638 an in vitro model system 1615:1638 an in vitro model system of these two stages of composite stone formation to study the role that various acidic macromolecules may play 1615:1749 Therefore, our goal is to develop an in vitro model system of these two stages of composite stone formation to study the role that various acidic macromolecules may play. 25119505 6 81 theme acidic 1419:1424 arg1 proteins 1426:1433 many acidic proteins 1414:1433 many acidic proteins 1414:1433 Given that there are many acidic proteins and polysaccharides present in the renal tissue and urine, we have put forth the hypothesis that the PILP system may be involved in urolithiasis. 25119505 1 82 theme plaque 141:146 arg1 deposits 153:160 Randall's plaque (RP) deposits 131:160 Randall's plaque (RP) deposits 131:160 Randall's plaque (RP) deposits seem to be consistent among the most common type of kidney stone formers, idiopathic calcium oxalate stone formers. 25119505 13 83 theme detrimental 3156:3166 arg1 consequences 3168:3179 its detrimental consequences 3152:3179 its detrimental consequences in stone formation 3152:3198 We believe that mineralization of native tissue scaffolds is useful for developing a model system of stone formation, with the ultimate goal of developing strategies to avoid RP and its detrimental consequences in stone formation, or developing therapeutic treatments to prevent or cure the disease. 25119505 13 84 from consequences 3168:3179 arg1 formation 3190:3198 stone formation 3184:3198 stone formation 3184:3198 We believe that mineralization of native tissue scaffolds is useful for developing a model system of stone formation, with the ultimate goal of developing strategies to avoid RP and its detrimental consequences in stone formation, or developing therapeutic treatments to prevent or cure the disease. 25119505 7 85 theme in 1618:1619 arg1 system 1633:1638 an in vitro model system 1615:1638 an in vitro model system of these two stages of composite stone formation to study the role that various acidic macromolecules may play 1615:1749 Therefore, our goal is to develop an in vitro model system of these two stages of composite stone formation to study the role that various acidic macromolecules may play. 25119505 10 86 theme striking 2408:2415 arg1 resemblance 2417:2427 a striking resemblance 2406:2427 a striking resemblance to native RP, which was not seen in the tissue mineralized via the classical crystal nucleation and growth process 2406:2542 We found that when using the PILP process to mineralize this tissue matrix, the two sides led to dramatically different mineral textures, and they bore a striking resemblance to native RP, which was not seen in the tissue mineralized via the classical crystal nucleation and growth process. 25119505 1 87 theme RP 149:150 arg1 deposits 153:160 Randall's plaque (RP) deposits 131:160 Randall's plaque (RP) deposits 131:160 Randall's plaque (RP) deposits seem to be consistent among the most common type of kidney stone formers, idiopathic calcium oxalate stone formers. 25119505 10 88 dep tissue 2469:2474 arg1 mineralized 2476:2486 mineralized 2476:2486 mineralized 2476:2486 We found that when using the PILP process to mineralize this tissue matrix, the two sides led to dramatically different mineral textures, and they bore a striking resemblance to native RP, which was not seen in the tissue mineralized via the classical crystal nucleation and growth process. 25119505 10 89 theme different 2364:2372 arg1 textures 2382:2389 dramatically different mineral textures 2351:2389 dramatically different mineral textures 2351:2389 We found that when using the PILP process to mineralize this tissue matrix, the two sides led to dramatically different mineral textures, and they bore a striking resemblance to native RP, which was not seen in the tissue mineralized via the classical crystal nucleation and growth process. 25119505 3 90 theme model 494:498 arg1 system 500:505 an in vitro model system 482:505 an in vitro model system to study idiopathic nephrolithiasis 482:541 Thus, the development of an in vitro model system to study idiopathic nephrolithiasis, beginning with RP pathogenesis, can help in identifying how plaques and subsequently stones form. 25119505 9 91 from mineral 2209:2215 arg1 stages 2230:2235 the early stages 2220:2235 the early stages of RP formation 2220:2251 To mimic the tissue environment, MatriStem(®) (ACell, Inc.), a decellularized porcine urinary bladder matrix was used, because it has both an intact epithelial basement membrane surface and a tunica propria layer, thus providing the two types of matrix constituents found associated with mineral in the early stages of RP formation. 25119505 13 92 theme stone 3184:3188 arg1 formation 3190:3198 stone formation 3184:3198 stone formation 3184:3198 We believe that mineralization of native tissue scaffolds is useful for developing a model system of stone formation, with the ultimate goal of developing strategies to avoid RP and its detrimental consequences in stone formation, or developing therapeutic treatments to prevent or cure the disease. 25119505 10 93 theme native 2432:2437 arg1 RP 2439:2440 native RP 2432:2440 native RP 2432:2440 We found that when using the PILP process to mineralize this tissue matrix, the two sides led to dramatically different mineral textures, and they bore a striking resemblance to native RP, which was not seen in the tissue mineralized via the classical crystal nucleation and growth process. 25119505 13 94 theme tissue 3011:3016 arg1 scaffolds 3018:3026 native tissue scaffolds 3004:3026 native tissue scaffolds 3004:3026 We believe that mineralization of native tissue scaffolds is useful for developing a model system of stone formation, with the ultimate goal of developing strategies to avoid RP and its detrimental consequences in stone formation, or developing therapeutic treatments to prevent or cure the disease. 25119505 0 95 theme stone 114:118 arg1 formation 120:128 idiopathic stone formation 103:128 idiopathic stone formation 103:128 Biomimetic Randall's plaque as an in vitro model system for studying the role of acidic biopolymers in idiopathic stone formation. 25119505 1 96 dep consistent 173:182 arg1 idiopathic 236:245 idiopathic 236:245 idiopathic 236:245 Randall's plaque (RP) deposits seem to be consistent among the most common type of kidney stone formers, idiopathic calcium oxalate stone formers. 25119505 14 97 theme grant 3289:3293 arg1 RO1DK092311 3295:3305 NIDDK grant RO1DK092311 3283:3305 NIDDK grant RO1DK092311 3283:3305 Supported by NIDDK grant RO1DK092311. 25119505 3 98 theme idiopathic 516:525 arg1 nephrolithiasis 527:541 idiopathic nephrolithiasis 516:541 idiopathic nephrolithiasis 516:541 Thus, the development of an in vitro model system to study idiopathic nephrolithiasis, beginning with RP pathogenesis, can help in identifying how plaques and subsequently stones form. 25119505 13 99 with useful 3031:3036 arg1 goal 3106:3109 the ultimate goal 3093:3109 the ultimate goal of developing strategies to avoid RP and its detrimental consequences in stone formation, or developing therapeutic treatments to prevent or cure the disease 3093:3267 We believe that mineralization of native tissue scaffolds is useful for developing a model system of stone formation, with the ultimate goal of developing strategies to avoid RP and its detrimental consequences in stone formation, or developing therapeutic treatments to prevent or cure the disease. 25119505 4 100 theme main 646:649 arg1 theory 651:656 One main theory 642:656 One main theory of RP formation 642:672 One main theory of RP formation is that calcium phosphate deposits initially form in the basement membrane of the thin loops of Henle, which then fuse and spread into the interstitial tissue, and ultimately make their way across the urothelium, where upon exposure to the urine, the mineralized tissue serves as a nidus for overgrowth with calcium oxalate into a stone. 25119505 5 101 theme collagenous 1155:1165 arg1 tissue 1167:1172 mineralized collagenous tissue 1143:1172 mineralized collagenous tissue 1143:1172 Our group has found that many of the unusual morphologies found in RP and stones, such as concentrically laminated spherulites and mineralized collagenous tissue, can be reproduced in vitro using a polymer-induced liquid precursor (PILP) process, in which acidic polypeptides induce a liquid phase amorphous precursor to the mineral, yielding non-equilibrium crystal morphologies. 25119505 3 102 dep in 485:486 arg1 vitro 488:492 vitro 488:492 vitro 488:492 Thus, the development of an in vitro model system to study idiopathic nephrolithiasis, beginning with RP pathogenesis, can help in identifying how plaques and subsequently stones form. 25119505 9 103 theme matrix 2167:2172 arg1 associated 2193:2202 associated 2193:2202 associated with mineral in the early stages of RP formation 2193:2251 To mimic the tissue environment, MatriStem(®) (ACell, Inc.), a decellularized porcine urinary bladder matrix was used, because it has both an intact epithelial basement membrane surface and a tunica propria layer, thus providing the two types of matrix constituents found associated with mineral in the early stages of RP formation. 25119505 9 103 theme matrix 2167:2172 arg1 constituents 2174:2185 matrix constituents 2167:2185 matrix constituents found associated with mineral in the early stages of RP formation 2167:2251 To mimic the tissue environment, MatriStem(®) (ACell, Inc.), a decellularized porcine urinary bladder matrix was used, because it has both an intact epithelial basement membrane surface and a tunica propria layer, thus providing the two types of matrix constituents found associated with mineral in the early stages of RP formation. 25119505 4 104 theme interstitial 813:824 arg1 tissue 826:831 the interstitial tissue 809:831 the interstitial tissue 809:831 One main theory of RP formation is that calcium phosphate deposits initially form in the basement membrane of the thin loops of Henle, which then fuse and spread into the interstitial tissue, and ultimately make their way across the urothelium, where upon exposure to the urine, the mineralized tissue serves as a nidus for overgrowth with calcium oxalate into a stone. 25119505 0 105 from role 73:76 arg1 formation 120:128 idiopathic stone formation 103:128 idiopathic stone formation 103:128 Biomimetic Randall's plaque as an in vitro model system for studying the role of acidic biopolymers in idiopathic stone formation. 25119505 9 106 theme porcine 1999:2005 arg1 bladder 2015:2021 a decellularized porcine urinary bladder 1982:2021 a decellularized porcine urinary bladder matrix 1982:2028 To mimic the tissue environment, MatriStem(®) (ACell, Inc.), a decellularized porcine urinary bladder matrix was used, because it has both an intact epithelial basement membrane surface and a tunica propria layer, thus providing the two types of matrix constituents found associated with mineral in the early stages of RP formation. 25119505 9 107 theme early 2224:2228 arg1 stages 2230:2235 the early stages 2220:2235 the early stages of RP formation 2220:2251 To mimic the tissue environment, MatriStem(®) (ACell, Inc.), a decellularized porcine urinary bladder matrix was used, because it has both an intact epithelial basement membrane surface and a tunica propria layer, thus providing the two types of matrix constituents found associated with mineral in the early stages of RP formation. 25119505 6 108 theme present 1455:1461 arg1 proteins 1426:1433 many acidic proteins 1414:1433 many acidic proteins 1414:1433 Given that there are many acidic proteins and polysaccharides present in the renal tissue and urine, we have put forth the hypothesis that the PILP system may be involved in urolithiasis. 25119505 5 109 theme laminated 1117:1125 arg1 spherulites 1127:1137 concentrically laminated spherulites 1102:1137 concentrically laminated spherulites 1102:1137 Our group has found that many of the unusual morphologies found in RP and stones, such as concentrically laminated spherulites and mineralized collagenous tissue, can be reproduced in vitro using a polymer-induced liquid precursor (PILP) process, in which acidic polypeptides induce a liquid phase amorphous precursor to the mineral, yielding non-equilibrium crystal morphologies. 25119505 9 110 theme bladder 2015:2021 arg1 matrix 2023:2028 a decellularized porcine urinary bladder matrix 1982:2028 a decellularized porcine urinary bladder matrix 1982:2028 To mimic the tissue environment, MatriStem(®) (ACell, Inc.), a decellularized porcine urinary bladder matrix was used, because it has both an intact epithelial basement membrane surface and a tunica propria layer, thus providing the two types of matrix constituents found associated with mineral in the early stages of RP formation. 25119505 5 111 theme non-equilibrium 1355:1369 arg1 morphologies 1379:1390 non-equilibrium crystal morphologies 1355:1390 non-equilibrium crystal morphologies 1355:1390 Our group has found that many of the unusual morphologies found in RP and stones, such as concentrically laminated spherulites and mineralized collagenous tissue, can be reproduced in vitro using a polymer-induced liquid precursor (PILP) process, in which acidic polypeptides induce a liquid phase amorphous precursor to the mineral, yielding non-equilibrium crystal morphologies. 25119505 8 112 theme " 1825:1825 arg1 development 1799:1809 the development 1795:1809 the development of "biomimetic" RP 1795:1828 In our initial experiments presented here, the development of "biomimetic" RP was investigated, which will then serve as a nidus for calcium oxalate overgrowth studies. 25119505 4 113 with overgrowth 966:975 arg1 oxalate 990:996 calcium oxalate 982:996 calcium oxalate into a stone 982:1009 One main theory of RP formation is that calcium phosphate deposits initially form in the basement membrane of the thin loops of Henle, which then fuse and spread into the interstitial tissue, and ultimately make their way across the urothelium, where upon exposure to the urine, the mineralized tissue serves as a nidus for overgrowth with calcium oxalate into a stone. 25119505 9 114 theme constituents 2174:2185 arg1 types 2158:2162 the two types 2150:2162 the two types of matrix constituents found associated with mineral in the early stages of RP formation 2150:2251 To mimic the tissue environment, MatriStem(®) (ACell, Inc.), a decellularized porcine urinary bladder matrix was used, because it has both an intact epithelial basement membrane surface and a tunica propria layer, thus providing the two types of matrix constituents found associated with mineral in the early stages of RP formation. 25119505 4 115 theme phosphate 690:698 arg1 deposits 700:707 calcium phosphate deposits 682:707 calcium phosphate deposits 682:707 One main theory of RP formation is that calcium phosphate deposits initially form in the basement membrane of the thin loops of Henle, which then fuse and spread into the interstitial tissue, and ultimately make their way across the urothelium, where upon exposure to the urine, the mineralized tissue serves as a nidus for overgrowth with calcium oxalate into a stone. 25119505 12 116 theme urinary 2949:2955 arg1 environment 2957:2967 the urinary environment 2945:2967 the urinary environment 2945:2967 Although these studies are only preliminary, they support our hypothesis that kidney stones may involve non-classical crystallization pathways induced by the large variety of macromolecular species in the urinary environment. 25119505 0 117 theme acidic 81:86 arg1 biopolymers 88:98 acidic biopolymers 81:98 acidic biopolymers 81:98 Biomimetic Randall's plaque as an in vitro model system for studying the role of acidic biopolymers in idiopathic stone formation. 25119505 5 118 located found 1070:1074 arg1 stones 1086:1091 stones 1086:1091 stones 1086:1091 Our group has found that many of the unusual morphologies found in RP and stones, such as concentrically laminated spherulites and mineralized collagenous tissue, can be reproduced in vitro using a polymer-induced liquid precursor (PILP) process, in which acidic polypeptides induce a liquid phase amorphous precursor to the mineral, yielding non-equilibrium crystal morphologies. 25119505 5 118 located found 1070:1074 arg1 tissue 1167:1172 mineralized collagenous tissue 1143:1172 mineralized collagenous tissue 1143:1172 Our group has found that many of the unusual morphologies found in RP and stones, such as concentrically laminated spherulites and mineralized collagenous tissue, can be reproduced in vitro using a polymer-induced liquid precursor (PILP) process, in which acidic polypeptides induce a liquid phase amorphous precursor to the mineral, yielding non-equilibrium crystal morphologies. 25119505 5 118 located found 1070:1074 arg2 morphologies 1057:1068 the unusual morphologies 1045:1068 the unusual morphologies found in RP and stones, such as concentrically laminated spherulites and mineralized collagenous tissue, 1045:1173 Our group has found that many of the unusual morphologies found in RP and stones, such as concentrically laminated spherulites and mineralized collagenous tissue, can be reproduced in vitro using a polymer-induced liquid precursor (PILP) process, in which acidic polypeptides induce a liquid phase amorphous precursor to the mineral, yielding non-equilibrium crystal morphologies. 25119505 5 118 located found 1070:1074 arg1 RP 1079:1080 RP 1079:1080 RP 1079:1080 Our group has found that many of the unusual morphologies found in RP and stones, such as concentrically laminated spherulites and mineralized collagenous tissue, can be reproduced in vitro using a polymer-induced liquid precursor (PILP) process, in which acidic polypeptides induce a liquid phase amorphous precursor to the mineral, yielding non-equilibrium crystal morphologies. 25119505 5 118 located found 1070:1074 arg1 spherulites 1127:1137 concentrically laminated spherulites 1102:1137 concentrically laminated spherulites 1102:1137 Our group has found that many of the unusual morphologies found in RP and stones, such as concentrically laminated spherulites and mineralized collagenous tissue, can be reproduced in vitro using a polymer-induced liquid precursor (PILP) process, in which acidic polypeptides induce a liquid phase amorphous precursor to the mineral, yielding non-equilibrium crystal morphologies. 25119505 5 119 theme polymer-induced 1210:1224 arg1 process 1250:1256 a polymer-induced liquid precursor (PILP) process 1208:1256 a polymer-induced liquid precursor (PILP) process 1208:1256 Our group has found that many of the unusual morphologies found in RP and stones, such as concentrically laminated spherulites and mineralized collagenous tissue, can be reproduced in vitro using a polymer-induced liquid precursor (PILP) process, in which acidic polypeptides induce a liquid phase amorphous precursor to the mineral, yielding non-equilibrium crystal morphologies. 25119505 2 120 theme systemic 336:343 arg1 symptoms 345:352 any systemic symptoms 332:352 any systemic symptoms 332:352 This group forms calcium oxalate renal stones without any systemic symptoms, which contributes to the difficulty of understanding and treating this painful and recurring disease. 25119505 13 121 theme ultimate 3097:3104 arg1 goal 3106:3109 the ultimate goal 3093:3109 the ultimate goal of developing strategies to avoid RP and its detrimental consequences in stone formation, or developing therapeutic treatments to prevent or cure the disease 3093:3267 We believe that mineralization of native tissue scaffolds is useful for developing a model system of stone formation, with the ultimate goal of developing strategies to avoid RP and its detrimental consequences in stone formation, or developing therapeutic treatments to prevent or cure the disease. 25119505 8 122 theme oxalate 1893:1899 arg1 studies 1912:1918 calcium oxalate overgrowth studies 1885:1918 calcium oxalate overgrowth studies 1885:1918 In our initial experiments presented here, the development of "biomimetic" RP was investigated, which will then serve as a nidus for calcium oxalate overgrowth studies. 25119505 8 123 theme initial 1759:1765 arg1 experiments 1767:1777 our initial experiments 1755:1777 our initial experiments presented here 1755:1792 In our initial experiments presented here, the development of "biomimetic" RP was investigated, which will then serve as a nidus for calcium oxalate overgrowth studies. 25119505 4 124 theme formation 664:672 arg1 theory 651:656 One main theory 642:656 One main theory of RP formation 642:672 One main theory of RP formation is that calcium phosphate deposits initially form in the basement membrane of the thin loops of Henle, which then fuse and spread into the interstitial tissue, and ultimately make their way across the urothelium, where upon exposure to the urine, the mineralized tissue serves as a nidus for overgrowth with calcium oxalate into a stone. 25119505 1 125 theme formers 227:233 arg1 type 206:209 the most common type 190:209 the most common type of kidney stone formers 190:233 Randall's plaque (RP) deposits seem to be consistent among the most common type of kidney stone formers, idiopathic calcium oxalate stone formers. 25119505 11 126 theme luminal 2633:2639 arg1 side 2641:2644 the luminal side 2629:2644 the luminal side 2629:2644 The interstitium side predominantly consisted of collagen-associated mineral, while the luminal side had much less mineral, which appeared to be tiny spherules embedded within the basement membrane. 25119505 4 127 theme mineralized 925:935 arg1 nidus 956:960 a nidus 954:960 a nidus for overgrowth with calcium oxalate into a stone 954:1009 One main theory of RP formation is that calcium phosphate deposits initially form in the basement membrane of the thin loops of Henle, which then fuse and spread into the interstitial tissue, and ultimately make their way across the urothelium, where upon exposure to the urine, the mineralized tissue serves as a nidus for overgrowth with calcium oxalate into a stone. 25119505 4 127 theme mineralized 925:935 arg1 tissue 937:942 the mineralized tissue 921:942 the mineralized tissue 921:942 One main theory of RP formation is that calcium phosphate deposits initially form in the basement membrane of the thin loops of Henle, which then fuse and spread into the interstitial tissue, and ultimately make their way across the urothelium, where upon exposure to the urine, the mineralized tissue serves as a nidus for overgrowth with calcium oxalate into a stone. 25119505 10 128 theme crystal 2506:2512 arg1 nucleation 2514:2523 the classical crystal nucleation 2492:2523 the classical crystal nucleation 2492:2523 We found that when using the PILP process to mineralize this tissue matrix, the two sides led to dramatically different mineral textures, and they bore a striking resemblance to native RP, which was not seen in the tissue mineralized via the classical crystal nucleation and growth process. 25119505 9 129 theme intact 2063:2068 arg1 surface 2099:2105 an intact epithelial basement membrane surface 2060:2105 an intact epithelial basement membrane surface 2060:2105 To mimic the tissue environment, MatriStem(®) (ACell, Inc.), a decellularized porcine urinary bladder matrix was used, because it has both an intact epithelial basement membrane surface and a tunica propria layer, thus providing the two types of matrix constituents found associated with mineral in the early stages of RP formation. 25119505 7 130 theme acidic 1720:1725 arg1 macromolecules 1727:1740 various acidic macromolecules 1712:1740 various acidic macromolecules 1712:1740 Therefore, our goal is to develop an in vitro model system of these two stages of composite stone formation to study the role that various acidic macromolecules may play. 25119505 12 131 theme species 2934:2940 arg1 variety 2908:2914 the large variety 2898:2914 the large variety of macromolecular species in the urinary environment 2898:2967 Although these studies are only preliminary, they support our hypothesis that kidney stones may involve non-classical crystallization pathways induced by the large variety of macromolecular species in the urinary environment. 25119505 12 131 theme species 2934:2940 arg1 species 2934:2940 macromolecular species 2919:2940 macromolecular species in the urinary environment 2919:2967 Although these studies are only preliminary, they support our hypothesis that kidney stones may involve non-classical crystallization pathways induced by the large variety of macromolecular species in the urinary environment. 25119505 9 132 theme basement 2081:2088 arg1 surface 2099:2105 an intact epithelial basement membrane surface 2060:2105 an intact epithelial basement membrane surface 2060:2105 To mimic the tissue environment, MatriStem(®) (ACell, Inc.), a decellularized porcine urinary bladder matrix was used, because it has both an intact epithelial basement membrane surface and a tunica propria layer, thus providing the two types of matrix constituents found associated with mineral in the early stages of RP formation. 25119505 1 133 theme oxalate 255:261 arg1 formers 269:275 consistent among the most common type of kidney stone formers, idiopathic calcium oxalate stone formers 173:275 consistent among the most common type of kidney stone formers, idiopathic calcium oxalate stone formers 173:275 Randall's plaque (RP) deposits seem to be consistent among the most common type of kidney stone formers, idiopathic calcium oxalate stone formers. 25119505 4 134 theme thin 756:759 arg1 loops 761:765 the thin loops 752:765 the thin loops of Henle, which then fuse and spread into the interstitial tissue, and ultimately make their way across the urothelium, where upon exposure to the urine, the mineralized tissue serves as a nidus for overgrowth with calcium oxalate into a stone 752:1009 One main theory of RP formation is that calcium phosphate deposits initially form in the basement membrane of the thin loops of Henle, which then fuse and spread into the interstitial tissue, and ultimately make their way across the urothelium, where upon exposure to the urine, the mineralized tissue serves as a nidus for overgrowth with calcium oxalate into a stone. 25119505 13 135 theme model 3055:3059 arg1 system 3061:3066 a model system 3053:3066 a model system of stone formation 3053:3085 We believe that mineralization of native tissue scaffolds is useful for developing a model system of stone formation, with the ultimate goal of developing strategies to avoid RP and its detrimental consequences in stone formation, or developing therapeutic treatments to prevent or cure the disease. 25119505 0 136 dep plaque 21:26 arg1 system 49:54 an in vitro model system 31:54 an in vitro model system for studying the role of acidic biopolymers in idiopathic stone formation 31:128 Biomimetic Randall's plaque as an in vitro model system for studying the role of acidic biopolymers in idiopathic stone formation. 25119505 7 137 theme formation 1679:1687 arg1 stages 1653:1658 these two stages 1643:1658 these two stages of composite stone formation 1643:1687 Therefore, our goal is to develop an in vitro model system of these two stages of composite stone formation to study the role that various acidic macromolecules may play. 25119505 12 138 theme large 2902:2906 arg1 variety 2908:2914 the large variety 2898:2914 the large variety of macromolecular species in the urinary environment 2898:2967 Although these studies are only preliminary, they support our hypothesis that kidney stones may involve non-classical crystallization pathways induced by the large variety of macromolecular species in the urinary environment. 25119505 12 138 theme large 2902:2906 arg1 species 2934:2940 macromolecular species 2919:2940 macromolecular species in the urinary environment 2919:2967 Although these studies are only preliminary, they support our hypothesis that kidney stones may involve non-classical crystallization pathways induced by the large variety of macromolecular species in the urinary environment. 25119505 5 139 theme precursor 1233:1241 arg1 process 1250:1256 a polymer-induced liquid precursor (PILP) process 1208:1256 a polymer-induced liquid precursor (PILP) process 1208:1256 Our group has found that many of the unusual morphologies found in RP and stones, such as concentrically laminated spherulites and mineralized collagenous tissue, can be reproduced in vitro using a polymer-induced liquid precursor (PILP) process, in which acidic polypeptides induce a liquid phase amorphous precursor to the mineral, yielding non-equilibrium crystal morphologies. 25119505 9 140 theme propria 2120:2126 arg1 layer 2128:2132 a tunica propria layer 2111:2132 a tunica propria layer 2111:2132 To mimic the tissue environment, MatriStem(®) (ACell, Inc.), a decellularized porcine urinary bladder matrix was used, because it has both an intact epithelial basement membrane surface and a tunica propria layer, thus providing the two types of matrix constituents found associated with mineral in the early stages of RP formation. 25119505 13 141 theme therapeutic 3215:3225 arg1 treatments 3227:3236 developing therapeutic treatments 3204:3236 developing therapeutic treatments 3204:3236 We believe that mineralization of native tissue scaffolds is useful for developing a model system of stone formation, with the ultimate goal of developing strategies to avoid RP and its detrimental consequences in stone formation, or developing therapeutic treatments to prevent or cure the disease. 25119505 7 142 theme composite 1663:1671 arg1 formation 1679:1687 composite stone formation 1663:1687 composite stone formation 1663:1687 Therefore, our goal is to develop an in vitro model system of these two stages of composite stone formation to study the role that various acidic macromolecules may play. 25119505 12 143 theme non-classical 2848:2860 arg1 pathways 2878:2885 non-classical crystallization pathways 2848:2885 non-classical crystallization pathways induced by the large variety of macromolecular species in the urinary environment 2848:2967 Although these studies are only preliminary, they support our hypothesis that kidney stones may involve non-classical crystallization pathways induced by the large variety of macromolecular species in the urinary environment. 25119505 4 144 theme basement 731:738 arg1 membrane 740:747 the basement membrane 727:747 the basement membrane of the thin loops of Henle, which then fuse and spread into the interstitial tissue, and ultimately make their way across the urothelium, where upon exposure to the urine, the mineralized tissue serves as a nidus for overgrowth with calcium oxalate into a stone 727:1009 One main theory of RP formation is that calcium phosphate deposits initially form in the basement membrane of the thin loops of Henle, which then fuse and spread into the interstitial tissue, and ultimately make their way across the urothelium, where upon exposure to the urine, the mineralized tissue serves as a nidus for overgrowth with calcium oxalate into a stone. 25119505 5 145 theme PILP 1244:1247 arg1 process 1250:1256 a polymer-induced liquid precursor (PILP) process 1208:1256 a polymer-induced liquid precursor (PILP) process 1208:1256 Our group has found that many of the unusual morphologies found in RP and stones, such as concentrically laminated spherulites and mineralized collagenous tissue, can be reproduced in vitro using a polymer-induced liquid precursor (PILP) process, in which acidic polypeptides induce a liquid phase amorphous precursor to the mineral, yielding non-equilibrium crystal morphologies. 25119505 2 146 theme renal 311:315 arg1 stones 317:322 calcium oxalate renal stones 295:322 calcium oxalate renal stones 295:322 This group forms calcium oxalate renal stones without any systemic symptoms, which contributes to the difficulty of understanding and treating this painful and recurring disease. 25119505 12 147 from environment 2957:2967 arg1 variety 2908:2914 the large variety 2898:2914 the large variety of macromolecular species in the urinary environment 2898:2967 Although these studies are only preliminary, they support our hypothesis that kidney stones may involve non-classical crystallization pathways induced by the large variety of macromolecular species in the urinary environment. 25119505 12 147 from environment 2957:2967 arg1 species 2934:2940 macromolecular species 2919:2940 macromolecular species in the urinary environment 2919:2967 Although these studies are only preliminary, they support our hypothesis that kidney stones may involve non-classical crystallization pathways induced by the large variety of macromolecular species in the urinary environment. 26370562 8 0 from expression 1174:1183 arg1 synoviocytes 1214:1225 synoviocytes 1214:1225 synoviocytes stimulated by TNF-α 1214:1245 RESULTS Hyper-O-GlcNAcylation increased the proliferation and mRNA expression of pro-inflammatory genes in synoviocytes stimulated by TNF-α. 26370562 7 1 theme cells 1086:1090 arg1 analysis 1072:1079 Fluorescence-activated cell sorting (FACS) analysis 1029:1079 Fluorescence-activated cell sorting (FACS) analysis of T cells 1029:1090 Fluorescence-activated cell sorting (FACS) analysis of T cells was performed. 26370562 11 2 with mice 1694:1697 arg1 CIA 1704:1706 CIA 1704:1706 CIA 1704:1706 CONCLUSIONS O-GlcNAcylation of p65 increased the effects of TNF-α-mediated inflammation both in vitro (in synovial cells) and in vivo (in mice with CIA). 26370562 8 3 theme mRNA 1169:1172 arg1 expression 1174:1183 mRNA expression 1169:1183 mRNA expression 1169:1183 RESULTS Hyper-O-GlcNAcylation increased the proliferation and mRNA expression of pro-inflammatory genes in synoviocytes stimulated by TNF-α. 26370562 0 4 link O-linked 0:7 arg1 N-acetylglucosamine 9:27 O-linked N-acetylglucosamine 0:27 O-linked N-acetylglucosamine glycosylation of p65 0:48 O-linked N-acetylglucosamine glycosylation of p65 aggravated the inflammation in both fibroblast-like synoviocytes stimulated by tumor necrosis factor-α and mice with collagen induced arthritis. 26370562 11 5 theme synovial 1662:1669 arg1 cells 1671:1675 synovial cells 1662:1675 synovial cells 1662:1675 CONCLUSIONS O-GlcNAcylation of p65 increased the effects of TNF-α-mediated inflammation both in vitro (in synovial cells) and in vivo (in mice with CIA). 26370562 10 6 theme arthritis 1445:1453 arg1 severity 1433:1440 the severity 1429:1440 the severity of arthritis 1429:1453 In CIA mice, ThiaMet-G significantly aggravated the severity of arthritis clinically and histologically, and it also increased CD4 + IFN-γ + T cells and CD4 + IL-17+ T cells. 26370562 1 7 theme rheumatoid 325:334 arg1 RA 347:348 RA 347:348 RA 347:348 INTRODUCTION We investigated the inflammatory potential of O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation) of p65 in rheumatoid arthritis (RA). 26370562 1 7 theme rheumatoid 325:334 arg1 arthritis 336:344 rheumatoid arthritis 325:344 rheumatoid arthritis (RA) 325:349 INTRODUCTION We investigated the inflammatory potential of O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation) of p65 in rheumatoid arthritis (RA). 26370562 1 8 from arthritis 336:344 arg1 potential 241:249 the inflammatory potential 224:249 the inflammatory potential of O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation) of p65 in rheumatoid arthritis (RA) 224:349 INTRODUCTION We investigated the inflammatory potential of O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation) of p65 in rheumatoid arthritis (RA). 26370562 8 9 theme genes 1205:1209 arg1 proliferation 1151:1163 proliferation 1151:1163 proliferation 1151:1163 RESULTS Hyper-O-GlcNAcylation increased the proliferation and mRNA expression of pro-inflammatory genes in synoviocytes stimulated by TNF-α. 26370562 8 9 theme genes 1205:1209 arg1 expression 1174:1183 mRNA expression 1169:1183 mRNA expression 1169:1183 RESULTS Hyper-O-GlcNAcylation increased the proliferation and mRNA expression of pro-inflammatory genes in synoviocytes stimulated by TNF-α. 26370562 6 10 theme ThiaMet-G 944:952 arg1 injection 981:989 ThiaMet-G (20 mg/kg) intraperitoneal injection 944:989 ThiaMet-G (20 mg/kg) intraperitoneal injection 944:989 ThiaMet-G (20 mg/kg) intraperitoneal injection was done every other day for 26 days. 26370562 6 10 theme ThiaMet-G 944:952 arg1 mg/kg 958:962 20 mg/kg 955:962 20 mg/kg 955:962 ThiaMet-G (20 mg/kg) intraperitoneal injection was done every other day for 26 days. 26370562 7 11 theme cell 1052:1055 arg1 FACS 1066:1069 FACS 1066:1069 FACS 1066:1069 Fluorescence-activated cell sorting (FACS) analysis of T cells was performed. 26370562 7 11 theme cell 1052:1055 arg1 sorting 1057:1063 Fluorescence-activated cell sorting 1029:1063 Fluorescence-activated cell sorting (FACS) analysis of T cells 1029:1090 Fluorescence-activated cell sorting (FACS) analysis of T cells was performed. 26370562 1 12 theme O-linked 254:261 arg1 N-acetylglucosamine 263:281 O-linked N-acetylglucosamine 254:281 O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation) of p65 in rheumatoid arthritis (RA) 254:349 INTRODUCTION We investigated the inflammatory potential of O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation) of p65 in rheumatoid arthritis (RA). 26370562 3 13 theme cells 570:574 arg1 Proliferation 544:556 Proliferation 544:556 Proliferation of synovial cells 544:574 Proliferation of synovial cells was measured by MTT assay, and the levels of mRNAs encoding pro-inflammatory molecules were quantitated by RT-PCR. 26370562 0 14 with mice 157:160 arg1 arthritis 184:192 collagen induced arthritis 167:192 collagen induced arthritis 167:192 O-linked N-acetylglucosamine glycosylation of p65 aggravated the inflammation in both fibroblast-like synoviocytes stimulated by tumor necrosis factor-α and mice with collagen induced arthritis. 26370562 1 15 from glycosylation 283:295 arg1 RA 347:348 RA 347:348 RA 347:348 INTRODUCTION We investigated the inflammatory potential of O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation) of p65 in rheumatoid arthritis (RA). 26370562 1 15 from glycosylation 283:295 arg1 arthritis 336:344 rheumatoid arthritis 325:344 rheumatoid arthritis (RA) 325:349 INTRODUCTION We investigated the inflammatory potential of O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation) of p65 in rheumatoid arthritis (RA). 26370562 9 16 theme p65 1277:1279 arg1 O-GlcNAcylation 1258:1272 O-GlcNAcylation 1258:1272 O-GlcNAcylation of p65 1258:1279 Moreover, O-GlcNAcylation of p65 enhanced its proportion of nuclear localization, DNA binding affinity and transcriptional activity. 26370562 6 17 theme other 1006:1010 arg1 day 1012:1014 every other day 1000:1014 every other day 1000:1014 ThiaMet-G (20 mg/kg) intraperitoneal injection was done every other day for 26 days. 26370562 2 18 theme necrosis 508:515 arg1 TNF 525:527 TNF 525:527 TNF 525:527 METHODS Fibroblast-like synoviocytes (FLS) and MH7A cells were treated with synthetic ThiaMet-G (200 μM), an O-GlcNAcase (OGA) inhibitor, followed by tumor necrosis factor (TNF)-α (10 μg/mL). 26370562 2 18 theme necrosis 508:515 arg1 factor 517:522 tumor necrosis factor 502:522 tumor necrosis factor (TNF)-α (10 μg/mL) 502:541 METHODS Fibroblast-like synoviocytes (FLS) and MH7A cells were treated with synthetic ThiaMet-G (200 μM), an O-GlcNAcase (OGA) inhibitor, followed by tumor necrosis factor (TNF)-α (10 μg/mL). 26370562 0 19 with factor-α 144:151 arg1 arthritis 184:192 collagen induced arthritis 167:192 collagen induced arthritis 167:192 O-linked N-acetylglucosamine glycosylation of p65 aggravated the inflammation in both fibroblast-like synoviocytes stimulated by tumor necrosis factor-α and mice with collagen induced arthritis. 26370562 3 20 theme MTT 592:594 arg1 assay 596:600 MTT assay 592:600 MTT assay 592:600 Proliferation of synovial cells was measured by MTT assay, and the levels of mRNAs encoding pro-inflammatory molecules were quantitated by RT-PCR. 26370562 0 21 theme fibroblast-like 86:100 arg1 synoviocytes 102:113 both fibroblast-like synoviocytes 81:113 both fibroblast-like synoviocytes stimulated by tumor necrosis factor-α and mice with collagen induced arthritis 81:192 O-linked N-acetylglucosamine glycosylation of p65 aggravated the inflammation in both fibroblast-like synoviocytes stimulated by tumor necrosis factor-α and mice with collagen induced arthritis. 26370562 1 22 gly glycosylation 283:295 arg1 RA 347:348 RA 347:348 RA 347:348 INTRODUCTION We investigated the inflammatory potential of O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation) of p65 in rheumatoid arthritis (RA). 26370562 1 22 gly glycosylation 283:295 arg1 p65 318:320 p65 318:320 p65 318:320 INTRODUCTION We investigated the inflammatory potential of O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation) of p65 in rheumatoid arthritis (RA). 26370562 1 22 gly glycosylation 283:295 arg1 arthritis 336:344 rheumatoid arthritis 325:344 rheumatoid arthritis (RA) 325:349 INTRODUCTION We investigated the inflammatory potential of O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation) of p65 in rheumatoid arthritis (RA). 26370562 8 23 dep proliferation 1151:1163 arg1 the 1147:1149 the 1147:1149 the 1147:1149 RESULTS Hyper-O-GlcNAcylation increased the proliferation and mRNA expression of pro-inflammatory genes in synoviocytes stimulated by TNF-α. 26370562 9 24 theme localization 1316:1327 arg1 proportion 1294:1303 its proportion 1290:1303 its proportion of nuclear localization, DNA binding affinity and transcriptional activity 1290:1378 Moreover, O-GlcNAcylation of p65 enhanced its proportion of nuclear localization, DNA binding affinity and transcriptional activity. 26370562 2 25 dep METHODS 352:358 arg1 FLS 390:392 FLS 390:392 FLS 390:392 METHODS Fibroblast-like synoviocytes (FLS) and MH7A cells were treated with synthetic ThiaMet-G (200 μM), an O-GlcNAcase (OGA) inhibitor, followed by tumor necrosis factor (TNF)-α (10 μg/mL). 26370562 2 25 dep METHODS 352:358 arg1 synoviocytes 376:387 Fibroblast-like synoviocytes 360:387 Fibroblast-like synoviocytes (FLS) 360:393 METHODS Fibroblast-like synoviocytes (FLS) and MH7A cells were treated with synthetic ThiaMet-G (200 μM), an O-GlcNAcase (OGA) inhibitor, followed by tumor necrosis factor (TNF)-α (10 μg/mL). 26370562 4 26 theme binding 753:759 arg1 affinity 761:768 its DNA binding affinity 745:768 its DNA binding affinity 745:768 The nuclear localization of O-GlcNAcylated of p65 and its DNA binding affinity and transcriptional activity were assessed. 26370562 0 27 theme tumor 129:133 arg1 factor-α 144:151 tumor necrosis factor-α 129:151 tumor necrosis factor-α 129:151 O-linked N-acetylglucosamine glycosylation of p65 aggravated the inflammation in both fibroblast-like synoviocytes stimulated by tumor necrosis factor-α and mice with collagen induced arthritis. 26370562 9 28 theme DNA 1330:1332 arg1 affinity 1342:1349 DNA binding affinity 1330:1349 DNA binding affinity 1330:1349 Moreover, O-GlcNAcylation of p65 enhanced its proportion of nuclear localization, DNA binding affinity and transcriptional activity. 26370562 8 29 dep RESULTS 1107:1113 arg1 increased 1137:1145 increased 1137:1145 increased the proliferation and mRNA expression of pro-inflammatory genes in synoviocytes stimulated by TNF-α 1137:1245 RESULTS Hyper-O-GlcNAcylation increased the proliferation and mRNA expression of pro-inflammatory genes in synoviocytes stimulated by TNF-α. 26370562 4 30 theme O-GlcNAcylated 719:732 arg1 localization 703:714 The nuclear localization 691:714 The nuclear localization of O-GlcNAcylated of p65 and its DNA binding affinity and transcriptional activity 691:797 The nuclear localization of O-GlcNAcylated of p65 and its DNA binding affinity and transcriptional activity were assessed. 26370562 0 31 theme O-linked 0:7 arg1 N-acetylglucosamine 9:27 O-linked N-acetylglucosamine 0:27 O-linked N-acetylglucosamine glycosylation of p65 0:48 O-linked N-acetylglucosamine glycosylation of p65 aggravated the inflammation in both fibroblast-like synoviocytes stimulated by tumor necrosis factor-α and mice with collagen induced arthritis. 26370562 9 32 theme affinity 1342:1349 arg1 proportion 1294:1303 its proportion 1290:1303 its proportion of nuclear localization, DNA binding affinity and transcriptional activity 1290:1378 Moreover, O-GlcNAcylation of p65 enhanced its proportion of nuclear localization, DNA binding affinity and transcriptional activity. 26370562 4 33 theme p65 737:739 arg1 O-GlcNAcylated 719:732 O-GlcNAcylated 719:732 O-GlcNAcylated 719:732 The nuclear localization of O-GlcNAcylated of p65 and its DNA binding affinity and transcriptional activity were assessed. 26370562 9 34 theme transcriptional 1355:1369 arg1 activity 1371:1378 transcriptional activity 1355:1378 transcriptional activity 1355:1378 Moreover, O-GlcNAcylation of p65 enhanced its proportion of nuclear localization, DNA binding affinity and transcriptional activity. 26370562 0 35 theme p65 46:48 arg1 glycosylation 29:41 O-linked N-acetylglucosamine glycosylation 0:41 O-linked N-acetylglucosamine glycosylation of p65 0:48 O-linked N-acetylglucosamine glycosylation of p65 aggravated the inflammation in both fibroblast-like synoviocytes stimulated by tumor necrosis factor-α and mice with collagen induced arthritis. 26370562 1 36 dep INTRODUCTION 195:206 arg1 investigated 211:222 investigated 211:222 investigated the inflammatory potential of O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation) of p65 in rheumatoid arthritis (RA) 211:349 INTRODUCTION We investigated the inflammatory potential of O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation) of p65 in rheumatoid arthritis (RA). 26370562 1 37 theme N-acetylglucosamine 263:281 arg1 O-GlcNAcylation 298:312 O-GlcNAcylation 298:312 O-GlcNAcylation 298:312 INTRODUCTION We investigated the inflammatory potential of O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation) of p65 in rheumatoid arthritis (RA). 26370562 1 37 theme N-acetylglucosamine 263:281 arg1 glycosylation 283:295 O-linked N-acetylglucosamine glycosylation 254:295 O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation) of p65 in rheumatoid arthritis (RA) 254:349 INTRODUCTION We investigated the inflammatory potential of O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation) of p65 in rheumatoid arthritis (RA). 26370562 8 38 from proliferation 1151:1163 arg1 synoviocytes 1214:1225 synoviocytes 1214:1225 synoviocytes stimulated by TNF-α 1214:1245 RESULTS Hyper-O-GlcNAcylation increased the proliferation and mRNA expression of pro-inflammatory genes in synoviocytes stimulated by TNF-α. 26370562 10 39 theme CIA 1384:1386 arg1 mice 1388:1391 CIA mice 1384:1391 CIA mice 1384:1391 In CIA mice, ThiaMet-G significantly aggravated the severity of arthritis clinically and histologically, and it also increased CD4 + IFN-γ + T cells and CD4 + IL-17+ T cells. 26370562 10 40 theme IL-17+ 1540:1545 arg1 cells 1549:1553 IL-17+ T cells 1540:1553 IL-17+ T cells 1540:1553 In CIA mice, ThiaMet-G significantly aggravated the severity of arthritis clinically and histologically, and it also increased CD4 + IFN-γ + T cells and CD4 + IL-17+ T cells. 26370562 11 41 theme TNF-α-mediated 1616:1629 arg1 inflammation 1631:1642 TNF-α-mediated inflammation 1616:1642 TNF-α-mediated inflammation 1616:1642 CONCLUSIONS O-GlcNAcylation of p65 increased the effects of TNF-α-mediated inflammation both in vitro (in synovial cells) and in vivo (in mice with CIA). 26370562 2 42 theme MH7A 399:402 arg1 cells 404:408 MH7A cells 399:408 MH7A cells 399:408 METHODS Fibroblast-like synoviocytes (FLS) and MH7A cells were treated with synthetic ThiaMet-G (200 μM), an O-GlcNAcase (OGA) inhibitor, followed by tumor necrosis factor (TNF)-α (10 μg/mL). 26370562 7 43 theme T 1084:1084 arg1 cells 1086:1090 T cells 1084:1090 T cells 1084:1090 Fluorescence-activated cell sorting (FACS) analysis of T cells was performed. 26370562 1 44 theme p65 318:320 arg1 O-GlcNAcylation 298:312 O-GlcNAcylation 298:312 O-GlcNAcylation 298:312 INTRODUCTION We investigated the inflammatory potential of O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation) of p65 in rheumatoid arthritis (RA). 26370562 1 44 theme p65 318:320 arg1 glycosylation 283:295 O-linked N-acetylglucosamine glycosylation 254:295 O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation) of p65 in rheumatoid arthritis (RA) 254:349 INTRODUCTION We investigated the inflammatory potential of O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation) of p65 in rheumatoid arthritis (RA). 26370562 2 45 theme Fibroblast-like 360:374 arg1 FLS 390:392 FLS 390:392 FLS 390:392 METHODS Fibroblast-like synoviocytes (FLS) and MH7A cells were treated with synthetic ThiaMet-G (200 μM), an O-GlcNAcase (OGA) inhibitor, followed by tumor necrosis factor (TNF)-α (10 μg/mL). 26370562 2 45 theme Fibroblast-like 360:374 arg1 synoviocytes 376:387 Fibroblast-like synoviocytes 360:387 Fibroblast-like synoviocytes (FLS) 360:393 METHODS Fibroblast-like synoviocytes (FLS) and MH7A cells were treated with synthetic ThiaMet-G (200 μM), an O-GlcNAcase (OGA) inhibitor, followed by tumor necrosis factor (TNF)-α (10 μg/mL). 26370562 5 46 theme histopathological 857:873 arg1 examination 875:885 a histopathological examination 855:885 a histopathological examination 855:885 The severity assessment of arthritis and a histopathological examination were done in mice with collagen induced arthritis (CIA). 26370562 5 47 with mice 900:903 arg1 CIA 938:940 CIA 938:940 CIA 938:940 The severity assessment of arthritis and a histopathological examination were done in mice with collagen induced arthritis (CIA). 26370562 5 47 with mice 900:903 arg1 arthritis 927:935 collagen induced arthritis 910:935 collagen induced arthritis (CIA) 910:941 The severity assessment of arthritis and a histopathological examination were done in mice with collagen induced arthritis (CIA). 26370562 7 48 theme sorting 1057:1063 arg1 analysis 1072:1079 Fluorescence-activated cell sorting (FACS) analysis 1029:1079 Fluorescence-activated cell sorting (FACS) analysis of T cells 1029:1090 Fluorescence-activated cell sorting (FACS) analysis of T cells was performed. 26370562 11 49 theme CONCLUSIONS 1556:1566 arg1 O-GlcNAcylation 1568:1582 CONCLUSIONS O-GlcNAcylation 1556:1582 CONCLUSIONS O-GlcNAcylation of p65 1556:1589 CONCLUSIONS O-GlcNAcylation of p65 increased the effects of TNF-α-mediated inflammation both in vitro (in synovial cells) and in vivo (in mice with CIA). 26370562 1 50 theme inflammatory 228:239 arg1 potential 241:249 the inflammatory potential 224:249 the inflammatory potential of O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation) of p65 in rheumatoid arthritis (RA) 224:349 INTRODUCTION We investigated the inflammatory potential of O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation) of p65 in rheumatoid arthritis (RA). 26370562 8 51 theme pro-inflammatory 1188:1203 arg1 genes 1205:1209 pro-inflammatory genes 1188:1209 pro-inflammatory genes 1188:1209 RESULTS Hyper-O-GlcNAcylation increased the proliferation and mRNA expression of pro-inflammatory genes in synoviocytes stimulated by TNF-α. 26370562 7 52 theme Fluorescence-activated 1029:1050 arg1 FACS 1066:1069 FACS 1066:1069 FACS 1066:1069 Fluorescence-activated cell sorting (FACS) analysis of T cells was performed. 26370562 7 52 theme Fluorescence-activated 1029:1050 arg1 sorting 1057:1063 Fluorescence-activated cell sorting 1029:1063 Fluorescence-activated cell sorting (FACS) analysis of T cells 1029:1090 Fluorescence-activated cell sorting (FACS) analysis of T cells was performed. 26370562 0 53 theme induced 176:182 arg1 arthritis 184:192 collagen induced arthritis 167:192 collagen induced arthritis 167:192 O-linked N-acetylglucosamine glycosylation of p65 aggravated the inflammation in both fibroblast-like synoviocytes stimulated by tumor necrosis factor-α and mice with collagen induced arthritis. 26370562 3 54 theme synovial 561:568 arg1 cells 570:574 synovial cells 561:574 synovial cells 561:574 Proliferation of synovial cells was measured by MTT assay, and the levels of mRNAs encoding pro-inflammatory molecules were quantitated by RT-PCR. 26370562 1 55 from potential 241:249 arg1 RA 347:348 RA 347:348 RA 347:348 INTRODUCTION We investigated the inflammatory potential of O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation) of p65 in rheumatoid arthritis (RA). 26370562 1 55 from potential 241:249 arg1 arthritis 336:344 rheumatoid arthritis 325:344 rheumatoid arthritis (RA) 325:349 INTRODUCTION We investigated the inflammatory potential of O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation) of p65 in rheumatoid arthritis (RA). 26370562 5 56 theme induced 919:925 arg1 CIA 938:940 CIA 938:940 CIA 938:940 The severity assessment of arthritis and a histopathological examination were done in mice with collagen induced arthritis (CIA). 26370562 5 56 theme induced 919:925 arg1 arthritis 927:935 collagen induced arthritis 910:935 collagen induced arthritis (CIA) 910:941 The severity assessment of arthritis and a histopathological examination were done in mice with collagen induced arthritis (CIA). 26370562 4 57 theme nuclear 695:701 arg1 localization 703:714 The nuclear localization 691:714 The nuclear localization of O-GlcNAcylated of p65 and its DNA binding affinity and transcriptional activity 691:797 The nuclear localization of O-GlcNAcylated of p65 and its DNA binding affinity and transcriptional activity were assessed. 26370562 5 58 theme severity 818:825 arg1 assessment 827:836 The severity assessment 814:836 The severity assessment of arthritis 814:849 The severity assessment of arthritis and a histopathological examination were done in mice with collagen induced arthritis (CIA). 26370562 2 59 theme tumor 502:506 arg1 TNF 525:527 TNF 525:527 TNF 525:527 METHODS Fibroblast-like synoviocytes (FLS) and MH7A cells were treated with synthetic ThiaMet-G (200 μM), an O-GlcNAcase (OGA) inhibitor, followed by tumor necrosis factor (TNF)-α (10 μg/mL). 26370562 2 59 theme tumor 502:506 arg1 factor 517:522 tumor necrosis factor 502:522 tumor necrosis factor (TNF)-α (10 μg/mL) 502:541 METHODS Fibroblast-like synoviocytes (FLS) and MH7A cells were treated with synthetic ThiaMet-G (200 μM), an O-GlcNAcase (OGA) inhibitor, followed by tumor necrosis factor (TNF)-α (10 μg/mL). 26370562 1 60 link O-linked 254:261 arg1 N-acetylglucosamine 263:281 O-linked N-acetylglucosamine 254:281 O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation) of p65 in rheumatoid arthritis (RA) 254:349 INTRODUCTION We investigated the inflammatory potential of O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation) of p65 in rheumatoid arthritis (RA). 26370562 9 61 theme nuclear 1308:1314 arg1 localization 1316:1327 nuclear localization 1308:1327 nuclear localization 1308:1327 Moreover, O-GlcNAcylation of p65 enhanced its proportion of nuclear localization, DNA binding affinity and transcriptional activity. 26370562 6 62 theme intraperitoneal 965:979 arg1 injection 981:989 ThiaMet-G (20 mg/kg) intraperitoneal injection 944:989 ThiaMet-G (20 mg/kg) intraperitoneal injection 944:989 ThiaMet-G (20 mg/kg) intraperitoneal injection was done every other day for 26 days. 26370562 6 62 theme intraperitoneal 965:979 arg1 mg/kg 958:962 20 mg/kg 955:962 20 mg/kg 955:962 ThiaMet-G (20 mg/kg) intraperitoneal injection was done every other day for 26 days. 26370562 0 63 from inflammation 65:76 arg1 synoviocytes 102:113 both fibroblast-like synoviocytes 81:113 both fibroblast-like synoviocytes stimulated by tumor necrosis factor-α and mice with collagen induced arthritis 81:192 O-linked N-acetylglucosamine glycosylation of p65 aggravated the inflammation in both fibroblast-like synoviocytes stimulated by tumor necrosis factor-α and mice with collagen induced arthritis. 26370562 2 64 dep treated 415:421 arg1 followed 490:497 followed 490:497 followed by tumor necrosis factor (TNF)-α (10 μg/mL) 490:541 METHODS Fibroblast-like synoviocytes (FLS) and MH7A cells were treated with synthetic ThiaMet-G (200 μM), an O-GlcNAcase (OGA) inhibitor, followed by tumor necrosis factor (TNF)-α (10 μg/mL). 26370562 0 65 theme necrosis 135:142 arg1 factor-α 144:151 tumor necrosis factor-α 129:151 tumor necrosis factor-α 129:151 O-linked N-acetylglucosamine glycosylation of p65 aggravated the inflammation in both fibroblast-like synoviocytes stimulated by tumor necrosis factor-α and mice with collagen induced arthritis. 26370562 2 66 theme factor 517:522 arg1 -α 529:530 tumor necrosis factor (TNF)-α 502:530 tumor necrosis factor (TNF)-α (10 μg/mL) 502:541 METHODS Fibroblast-like synoviocytes (FLS) and MH7A cells were treated with synthetic ThiaMet-G (200 μM), an O-GlcNAcase (OGA) inhibitor, followed by tumor necrosis factor (TNF)-α (10 μg/mL). 26370562 2 66 theme factor 517:522 arg1 μg/mL 536:540 10 μg/mL 533:540 10 μg/mL 533:540 METHODS Fibroblast-like synoviocytes (FLS) and MH7A cells were treated with synthetic ThiaMet-G (200 μM), an O-GlcNAcase (OGA) inhibitor, followed by tumor necrosis factor (TNF)-α (10 μg/mL). 26370562 4 67 theme DNA 749:751 arg1 affinity 761:768 its DNA binding affinity 745:768 its DNA binding affinity 745:768 The nuclear localization of O-GlcNAcylated of p65 and its DNA binding affinity and transcriptional activity were assessed. 26370562 2 68 theme synthetic 428:436 arg1 inhibitor 479:487 an O-GlcNAcase (OGA) inhibitor 458:487 an O-GlcNAcase (OGA) inhibitor 458:487 METHODS Fibroblast-like synoviocytes (FLS) and MH7A cells were treated with synthetic ThiaMet-G (200 μM), an O-GlcNAcase (OGA) inhibitor, followed by tumor necrosis factor (TNF)-α (10 μg/mL). 26370562 2 68 theme synthetic 428:436 arg1 ThiaMet-G 438:446 synthetic ThiaMet-G 428:446 synthetic ThiaMet-G (200 μM) 428:455 METHODS Fibroblast-like synoviocytes (FLS) and MH7A cells were treated with synthetic ThiaMet-G (200 μM), an O-GlcNAcase (OGA) inhibitor, followed by tumor necrosis factor (TNF)-α (10 μg/mL). 26370562 2 68 theme synthetic 428:436 arg1 μM 453:454 200 μM 449:454 200 μM 449:454 METHODS Fibroblast-like synoviocytes (FLS) and MH7A cells were treated with synthetic ThiaMet-G (200 μM), an O-GlcNAcase (OGA) inhibitor, followed by tumor necrosis factor (TNF)-α (10 μg/mL). 26370562 0 69 theme N-acetylglucosamine 9:27 arg1 glycosylation 29:41 O-linked N-acetylglucosamine glycosylation 0:41 O-linked N-acetylglucosamine glycosylation of p65 0:48 O-linked N-acetylglucosamine glycosylation of p65 aggravated the inflammation in both fibroblast-like synoviocytes stimulated by tumor necrosis factor-α and mice with collagen induced arthritis. 26370562 9 70 theme binding 1334:1340 arg1 affinity 1342:1349 DNA binding affinity 1330:1349 DNA binding affinity 1330:1349 Moreover, O-GlcNAcylation of p65 enhanced its proportion of nuclear localization, DNA binding affinity and transcriptional activity. 26370562 2 71 theme O-GlcNAcase 461:471 arg1 ThiaMet-G 438:446 synthetic ThiaMet-G 428:446 synthetic ThiaMet-G (200 μM) 428:455 METHODS Fibroblast-like synoviocytes (FLS) and MH7A cells were treated with synthetic ThiaMet-G (200 μM), an O-GlcNAcase (OGA) inhibitor, followed by tumor necrosis factor (TNF)-α (10 μg/mL). 26370562 2 71 theme O-GlcNAcase 461:471 arg1 inhibitor 479:487 an O-GlcNAcase (OGA) inhibitor 458:487 an O-GlcNAcase (OGA) inhibitor 458:487 METHODS Fibroblast-like synoviocytes (FLS) and MH7A cells were treated with synthetic ThiaMet-G (200 μM), an O-GlcNAcase (OGA) inhibitor, followed by tumor necrosis factor (TNF)-α (10 μg/mL). 26370562 11 72 dep vitro 1652:1656 arg1 cells 1671:1675 synovial cells 1662:1675 synovial cells 1662:1675 CONCLUSIONS O-GlcNAcylation of p65 increased the effects of TNF-α-mediated inflammation both in vitro (in synovial cells) and in vivo (in mice with CIA). 26370562 9 73 theme activity 1371:1378 arg1 proportion 1294:1303 its proportion 1290:1303 its proportion of nuclear localization, DNA binding affinity and transcriptional activity 1290:1378 Moreover, O-GlcNAcylation of p65 enhanced its proportion of nuclear localization, DNA binding affinity and transcriptional activity. 26370562 0 74 gly glycosylation 29:41 arg1 p65 46:48 p65 46:48 p65 46:48 O-linked N-acetylglucosamine glycosylation of p65 aggravated the inflammation in both fibroblast-like synoviocytes stimulated by tumor necrosis factor-α and mice with collagen induced arthritis. 26370562 2 75 theme OGA 474:476 arg1 ThiaMet-G 438:446 synthetic ThiaMet-G 428:446 synthetic ThiaMet-G (200 μM) 428:455 METHODS Fibroblast-like synoviocytes (FLS) and MH7A cells were treated with synthetic ThiaMet-G (200 μM), an O-GlcNAcase (OGA) inhibitor, followed by tumor necrosis factor (TNF)-α (10 μg/mL). 26370562 2 75 theme OGA 474:476 arg1 inhibitor 479:487 an O-GlcNAcase (OGA) inhibitor 458:487 an O-GlcNAcase (OGA) inhibitor 458:487 METHODS Fibroblast-like synoviocytes (FLS) and MH7A cells were treated with synthetic ThiaMet-G (200 μM), an O-GlcNAcase (OGA) inhibitor, followed by tumor necrosis factor (TNF)-α (10 μg/mL). 26370562 3 76 theme pro-inflammatory 636:651 arg1 molecules 653:661 pro-inflammatory molecules 636:661 pro-inflammatory molecules 636:661 Proliferation of synovial cells was measured by MTT assay, and the levels of mRNAs encoding pro-inflammatory molecules were quantitated by RT-PCR. 26370562 11 77 theme p65 1587:1589 arg1 O-GlcNAcylation 1568:1582 CONCLUSIONS O-GlcNAcylation 1556:1582 CONCLUSIONS O-GlcNAcylation of p65 1556:1589 CONCLUSIONS O-GlcNAcylation of p65 increased the effects of TNF-α-mediated inflammation both in vitro (in synovial cells) and in vivo (in mice with CIA). 26370562 10 78 theme T 1522:1522 arg1 cells 1524:1528 T cells 1522:1528 T cells 1522:1528 In CIA mice, ThiaMet-G significantly aggravated the severity of arthritis clinically and histologically, and it also increased CD4 + IFN-γ + T cells and CD4 + IL-17+ T cells. 26370562 3 79 theme mRNAs 621:625 arg1 levels 611:616 the levels 607:616 the levels of mRNAs encoding pro-inflammatory molecules 607:661 Proliferation of synovial cells was measured by MTT assay, and the levels of mRNAs encoding pro-inflammatory molecules were quantitated by RT-PCR. 26370562 4 80 theme affinity 761:768 arg1 O-GlcNAcylated 719:732 O-GlcNAcylated 719:732 O-GlcNAcylated 719:732 The nuclear localization of O-GlcNAcylated of p65 and its DNA binding affinity and transcriptional activity were assessed. 26370562 11 81 theme inflammation 1631:1642 arg1 effects 1605:1611 the effects 1601:1611 the effects of TNF-α-mediated inflammation 1601:1642 CONCLUSIONS O-GlcNAcylation of p65 increased the effects of TNF-α-mediated inflammation both in vitro (in synovial cells) and in vivo (in mice with CIA). 26370562 1 82 theme glycosylation 283:295 arg1 potential 241:249 the inflammatory potential 224:249 the inflammatory potential of O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation) of p65 in rheumatoid arthritis (RA) 224:349 INTRODUCTION We investigated the inflammatory potential of O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation) of p65 in rheumatoid arthritis (RA). 26370562 5 83 theme arthritis 841:849 arg1 assessment 827:836 The severity assessment 814:836 The severity assessment of arthritis 814:849 The severity assessment of arthritis and a histopathological examination were done in mice with collagen induced arthritis (CIA). 26370562 5 83 theme arthritis 841:849 arg1 examination 875:885 a histopathological examination 855:885 a histopathological examination 855:885 The severity assessment of arthritis and a histopathological examination were done in mice with collagen induced arthritis (CIA). 26370562 10 84 theme T 1547:1547 arg1 cells 1549:1553 IL-17+ T cells 1540:1553 IL-17+ T cells 1540:1553 In CIA mice, ThiaMet-G significantly aggravated the severity of arthritis clinically and histologically, and it also increased CD4 + IFN-γ + T cells and CD4 + IL-17+ T cells. 26370562 4 85 theme transcriptional 774:788 arg1 activity 790:797 transcriptional activity 774:797 transcriptional activity 774:797 The nuclear localization of O-GlcNAcylated of p65 and its DNA binding affinity and transcriptional activity were assessed. 27399888 2 0 dep yields 627:632 arg1 to 614:615 to 614:615 to 614:615 The salient features of this protocol are that it allows direct and rapid access to unprecedented diverse fused THIQ skeletons, is metal/catalyst free, has a cleaner reaction profile, provides good to excellent yields, and is a convenient approach. 27399888 1 1 theme first 404:408 arg1 time 410:413 the first time 400:413 the first time 400:413 A branching double-annulation cascade (BDAC) strategy for diverse and complex fused THIQ scaffolds via a highly reactive iminium-induced one-pot double-cyclization sequence involving Pictect-Spengler-type cyclization has been developed for the first time. 27399888 2 2 theme salient 420:426 arg1 features 428:435 The salient features 416:435 The salient features of this protocol 416:452 The salient features of this protocol are that it allows direct and rapid access to unprecedented diverse fused THIQ skeletons, is metal/catalyst free, has a cleaner reaction profile, provides good to excellent yields, and is a convenient approach. 27399888 1 3 theme reactive 272:279 arg1 sequence 324:331 a highly reactive iminium-induced one-pot double-cyclization sequence 263:331 a highly reactive iminium-induced one-pot double-cyclization sequence involving Pictect-Spengler-type cyclization 263:375 A branching double-annulation cascade (BDAC) strategy for diverse and complex fused THIQ scaffolds via a highly reactive iminium-induced one-pot double-cyclization sequence involving Pictect-Spengler-type cyclization has been developed for the first time. 27399888 0 4 theme One-Pot 91:97 arg1 Synthesis 99:107 Iminium-Induced One-Pot Synthesis 75:107 Scaffold Diversity through a Branching Double-Annulation Cascade Strategy: Iminium-Induced One-Pot Synthesis of Diverse Fused Tetrahydroisoquinoline Scaffolds. 0:158 Scaffold Diversity through a Branching Double-Annulation Cascade Strategy: Iminium-Induced One-Pot Synthesis of Diverse Fused Tetrahydroisoquinoline Scaffolds. 27399888 1 5 theme BDAC 199:202 arg1 strategy 205:212 A branching double-annulation cascade (BDAC) strategy 160:212 A branching double-annulation cascade (BDAC) strategy for diverse and complex fused THIQ scaffolds via a highly reactive iminium-induced one-pot double-cyclization sequence involving Pictect-Spengler-type cyclization 160:375 A branching double-annulation cascade (BDAC) strategy for diverse and complex fused THIQ scaffolds via a highly reactive iminium-induced one-pot double-cyclization sequence involving Pictect-Spengler-type cyclization has been developed for the first time. 27399888 3 6 theme uniform 852:858 arg1 conditions 869:878 uniform reaction conditions 852:878 uniform reaction conditions 852:878 This catalyst-free domino process facilitates the double annulation with a variety of scaffold building agents via two C-N and one C-X (X = C, N, O) bond formation in a single step under uniform reaction conditions. 27399888 1 7 theme iminium-induced 281:295 arg1 sequence 324:331 a highly reactive iminium-induced one-pot double-cyclization sequence 263:331 a highly reactive iminium-induced one-pot double-cyclization sequence involving Pictect-Spengler-type cyclization 263:375 A branching double-annulation cascade (BDAC) strategy for diverse and complex fused THIQ scaffolds via a highly reactive iminium-induced one-pot double-cyclization sequence involving Pictect-Spengler-type cyclization has been developed for the first time. 27399888 0 8 theme Diverse 112:118 arg1 Scaffolds 149:157 Diverse Fused Tetrahydroisoquinoline Scaffolds 112:157 Diverse Fused Tetrahydroisoquinoline Scaffolds 112:157 Scaffold Diversity through a Branching Double-Annulation Cascade Strategy: Iminium-Induced One-Pot Synthesis of Diverse Fused Tetrahydroisoquinoline Scaffolds. 27399888 3 9 theme reaction 860:867 arg1 conditions 869:878 uniform reaction conditions 852:878 uniform reaction conditions 852:878 This catalyst-free domino process facilitates the double annulation with a variety of scaffold building agents via two C-N and one C-X (X = C, N, O) bond formation in a single step under uniform reaction conditions. 27399888 1 10 theme one-pot 297:303 arg1 sequence 324:331 a highly reactive iminium-induced one-pot double-cyclization sequence 263:331 a highly reactive iminium-induced one-pot double-cyclization sequence involving Pictect-Spengler-type cyclization 263:375 A branching double-annulation cascade (BDAC) strategy for diverse and complex fused THIQ scaffolds via a highly reactive iminium-induced one-pot double-cyclization sequence involving Pictect-Spengler-type cyclization has been developed for the first time. 27399888 1 11 theme double-cyclization 305:322 arg1 sequence 324:331 a highly reactive iminium-induced one-pot double-cyclization sequence 263:331 a highly reactive iminium-induced one-pot double-cyclization sequence involving Pictect-Spengler-type cyclization 263:375 A branching double-annulation cascade (BDAC) strategy for diverse and complex fused THIQ scaffolds via a highly reactive iminium-induced one-pot double-cyclization sequence involving Pictect-Spengler-type cyclization has been developed for the first time. 27399888 0 12 theme Tetrahydroisoquinoline 126:147 arg1 Scaffolds 149:157 Diverse Fused Tetrahydroisoquinoline Scaffolds 112:157 Diverse Fused Tetrahydroisoquinoline Scaffolds 112:157 Scaffold Diversity through a Branching Double-Annulation Cascade Strategy: Iminium-Induced One-Pot Synthesis of Diverse Fused Tetrahydroisoquinoline Scaffolds. 27399888 2 13 theme direct 473:478 arg1 access 490:495 direct and rapid access 473:495 direct and rapid access to unprecedented diverse fused THIQ skeletons 473:541 The salient features of this protocol are that it allows direct and rapid access to unprecedented diverse fused THIQ skeletons, is metal/catalyst free, has a cleaner reaction profile, provides good to excellent yields, and is a convenient approach. 27399888 0 14 theme Fused 120:124 arg1 Scaffolds 149:157 Diverse Fused Tetrahydroisoquinoline Scaffolds 112:157 Diverse Fused Tetrahydroisoquinoline Scaffolds 112:157 Scaffold Diversity through a Branching Double-Annulation Cascade Strategy: Iminium-Induced One-Pot Synthesis of Diverse Fused Tetrahydroisoquinoline Scaffolds. 27399888 3 15 theme building 760:767 arg1 agents 769:774 scaffold building agents 751:774 scaffold building agents 751:774 This catalyst-free domino process facilitates the double annulation with a variety of scaffold building agents via two C-N and one C-X (X = C, N, O) bond formation in a single step under uniform reaction conditions. 27399888 3 16 with annulation 722:731 arg1 agents 769:774 scaffold building agents 751:774 scaffold building agents 751:774 This catalyst-free domino process facilitates the double annulation with a variety of scaffold building agents via two C-N and one C-X (X = C, N, O) bond formation in a single step under uniform reaction conditions. 27399888 3 16 with annulation 722:731 arg1 variety 740:746 a variety 738:746 a variety of scaffold building agents 738:774 This catalyst-free domino process facilitates the double annulation with a variety of scaffold building agents via two C-N and one C-X (X = C, N, O) bond formation in a single step under uniform reaction conditions. 27399888 4 17 theme N-N-linked 945:954 arg1 dimer 969:973 N-N-linked isoquinoline dimer 945:973 N-N-linked isoquinoline dimer 945:973 Furthermore, we reveal an unusual dual BDAC sequence leading to N-N-linked isoquinoline dimer. 27399888 2 18 theme unprecedented 500:512 arg1 skeletons 533:541 unprecedented diverse fused THIQ skeletons 500:541 unprecedented diverse fused THIQ skeletons 500:541 The salient features of this protocol are that it allows direct and rapid access to unprecedented diverse fused THIQ skeletons, is metal/catalyst free, has a cleaner reaction profile, provides good to excellent yields, and is a convenient approach. 27399888 3 19 theme agents 769:774 arg1 agents 769:774 scaffold building agents 751:774 scaffold building agents 751:774 This catalyst-free domino process facilitates the double annulation with a variety of scaffold building agents via two C-N and one C-X (X = C, N, O) bond formation in a single step under uniform reaction conditions. 27399888 3 19 theme agents 769:774 arg1 variety 740:746 a variety 738:746 a variety of scaffold building agents 738:774 This catalyst-free domino process facilitates the double annulation with a variety of scaffold building agents via two C-N and one C-X (X = C, N, O) bond formation in a single step under uniform reaction conditions. 27399888 2 20 theme protocol 445:452 arg1 features 428:435 The salient features 416:435 The salient features of this protocol 416:452 The salient features of this protocol are that it allows direct and rapid access to unprecedented diverse fused THIQ skeletons, is metal/catalyst free, has a cleaner reaction profile, provides good to excellent yields, and is a convenient approach. 27399888 0 21 theme Scaffold 0:7 arg1 Diversity 9:17 Scaffold Diversity 0:17 Scaffold Diversity through a Branching Double-Annulation Cascade Strategy: Iminium-Induced One-Pot Synthesis of Diverse Fused Tetrahydroisoquinoline Scaffolds. 0:158 Scaffold Diversity through a Branching Double-Annulation Cascade Strategy: Iminium-Induced One-Pot Synthesis of Diverse Fused Tetrahydroisoquinoline Scaffolds. 27399888 2 22 theme convenient 644:653 arg1 approach 655:662 a convenient approach 642:662 a convenient approach 642:662 The salient features of this protocol are that it allows direct and rapid access to unprecedented diverse fused THIQ skeletons, is metal/catalyst free, has a cleaner reaction profile, provides good to excellent yields, and is a convenient approach. 27399888 1 23 theme diverse 218:224 arg1 scaffolds 249:257 diverse and complex fused THIQ scaffolds 218:257 diverse and complex fused THIQ scaffolds 218:257 A branching double-annulation cascade (BDAC) strategy for diverse and complex fused THIQ scaffolds via a highly reactive iminium-induced one-pot double-cyclization sequence involving Pictect-Spengler-type cyclization has been developed for the first time. 27399888 4 24 theme unusual 907:913 arg1 sequence 925:932 an unusual dual BDAC sequence 904:932 an unusual dual BDAC sequence leading to N-N-linked isoquinoline dimer 904:973 Furthermore, we reveal an unusual dual BDAC sequence leading to N-N-linked isoquinoline dimer. 27399888 3 25 theme bond 814:817 arg1 formation 819:827 bond formation 814:827 bond formation 814:827 This catalyst-free domino process facilitates the double annulation with a variety of scaffold building agents via two C-N and one C-X (X = C, N, O) bond formation in a single step under uniform reaction conditions. 27399888 2 26 theme rapid 484:488 arg1 access 490:495 direct and rapid access 473:495 direct and rapid access to unprecedented diverse fused THIQ skeletons 473:541 The salient features of this protocol are that it allows direct and rapid access to unprecedented diverse fused THIQ skeletons, is metal/catalyst free, has a cleaner reaction profile, provides good to excellent yields, and is a convenient approach. 27399888 1 27 theme Pictect-Spengler-type 343:363 arg1 cyclization 365:375 Pictect-Spengler-type cyclization 343:375 Pictect-Spengler-type cyclization 343:375 A branching double-annulation cascade (BDAC) strategy for diverse and complex fused THIQ scaffolds via a highly reactive iminium-induced one-pot double-cyclization sequence involving Pictect-Spengler-type cyclization has been developed for the first time. 27399888 0 28 theme Scaffolds 149:157 arg1 Synthesis 99:107 Iminium-Induced One-Pot Synthesis 75:107 Scaffold Diversity through a Branching Double-Annulation Cascade Strategy: Iminium-Induced One-Pot Synthesis of Diverse Fused Tetrahydroisoquinoline Scaffolds. 0:158 Scaffold Diversity through a Branching Double-Annulation Cascade Strategy: Iminium-Induced One-Pot Synthesis of Diverse Fused Tetrahydroisoquinoline Scaffolds. 27399888 3 29 dep O 811:811 arg1 N 808:808 X = C, N, O 801:811 N 808:808 This catalyst-free domino process facilitates the double annulation with a variety of scaffold building agents via two C-N and one C-X (X = C, N, O) bond formation in a single step under uniform reaction conditions. 27399888 1 30 theme complex 230:236 arg1 scaffolds 249:257 diverse and complex fused THIQ scaffolds 218:257 diverse and complex fused THIQ scaffolds 218:257 A branching double-annulation cascade (BDAC) strategy for diverse and complex fused THIQ scaffolds via a highly reactive iminium-induced one-pot double-cyclization sequence involving Pictect-Spengler-type cyclization has been developed for the first time. 27399888 0 31 theme Double-Annulation 39:55 arg1 Strategy 65:72 a Branching Double-Annulation Cascade Strategy 27:72 a Branching Double-Annulation Cascade Strategy 27:72 Scaffold Diversity through a Branching Double-Annulation Cascade Strategy: Iminium-Induced One-Pot Synthesis of Diverse Fused Tetrahydroisoquinoline Scaffolds. 27399888 4 32 theme BDAC 920:923 arg1 sequence 925:932 an unusual dual BDAC sequence 904:932 an unusual dual BDAC sequence leading to N-N-linked isoquinoline dimer 904:973 Furthermore, we reveal an unusual dual BDAC sequence leading to N-N-linked isoquinoline dimer. 27399888 4 33 theme dual 915:918 arg1 sequence 925:932 an unusual dual BDAC sequence 904:932 an unusual dual BDAC sequence leading to N-N-linked isoquinoline dimer 904:973 Furthermore, we reveal an unusual dual BDAC sequence leading to N-N-linked isoquinoline dimer. 27399888 1 34 theme fused 238:242 arg1 scaffolds 249:257 diverse and complex fused THIQ scaffolds 218:257 diverse and complex fused THIQ scaffolds 218:257 A branching double-annulation cascade (BDAC) strategy for diverse and complex fused THIQ scaffolds via a highly reactive iminium-induced one-pot double-cyclization sequence involving Pictect-Spengler-type cyclization has been developed for the first time. 27399888 0 35 theme Branching 29:37 arg1 Strategy 65:72 a Branching Double-Annulation Cascade Strategy 27:72 a Branching Double-Annulation Cascade Strategy 27:72 Scaffold Diversity through a Branching Double-Annulation Cascade Strategy: Iminium-Induced One-Pot Synthesis of Diverse Fused Tetrahydroisoquinoline Scaffolds. 27399888 3 36 theme = 803:803 arg1 O 811:811 X = C, N, O 801:811 O 811:811 This catalyst-free domino process facilitates the double annulation with a variety of scaffold building agents via two C-N and one C-X (X = C, N, O) bond formation in a single step under uniform reaction conditions. 27399888 3 36 theme = 803:803 arg1 C-X 796:798 one C-X 792:798 one C-X (X = C, N, O) 792:812 This catalyst-free domino process facilitates the double annulation with a variety of scaffold building agents via two C-N and one C-X (X = C, N, O) bond formation in a single step under uniform reaction conditions. 27399888 2 37 theme THIQ 528:531 arg1 skeletons 533:541 unprecedented diverse fused THIQ skeletons 500:541 unprecedented diverse fused THIQ skeletons 500:541 The salient features of this protocol are that it allows direct and rapid access to unprecedented diverse fused THIQ skeletons, is metal/catalyst free, has a cleaner reaction profile, provides good to excellent yields, and is a convenient approach. 27399888 3 38 theme catalyst-free 670:682 arg1 process 691:697 This catalyst-free domino process 665:697 This catalyst-free domino process 665:697 This catalyst-free domino process facilitates the double annulation with a variety of scaffold building agents via two C-N and one C-X (X = C, N, O) bond formation in a single step under uniform reaction conditions. 27399888 2 39 theme reaction 582:589 arg1 profile 591:597 a cleaner reaction profile 572:597 a cleaner reaction profile 572:597 The salient features of this protocol are that it allows direct and rapid access to unprecedented diverse fused THIQ skeletons, is metal/catalyst free, has a cleaner reaction profile, provides good to excellent yields, and is a convenient approach. 27399888 1 40 theme THIQ 244:247 arg1 scaffolds 249:257 diverse and complex fused THIQ scaffolds 218:257 diverse and complex fused THIQ scaffolds 218:257 A branching double-annulation cascade (BDAC) strategy for diverse and complex fused THIQ scaffolds via a highly reactive iminium-induced one-pot double-cyclization sequence involving Pictect-Spengler-type cyclization has been developed for the first time. 27399888 2 41 theme fused 522:526 arg1 skeletons 533:541 unprecedented diverse fused THIQ skeletons 500:541 unprecedented diverse fused THIQ skeletons 500:541 The salient features of this protocol are that it allows direct and rapid access to unprecedented diverse fused THIQ skeletons, is metal/catalyst free, has a cleaner reaction profile, provides good to excellent yields, and is a convenient approach. 27399888 2 42 theme cleaner 574:580 arg1 profile 591:597 a cleaner reaction profile 572:597 a cleaner reaction profile 572:597 The salient features of this protocol are that it allows direct and rapid access to unprecedented diverse fused THIQ skeletons, is metal/catalyst free, has a cleaner reaction profile, provides good to excellent yields, and is a convenient approach. 27399888 4 43 link N-N-linked 945:954 arg1 dimer 969:973 N-N-linked isoquinoline dimer 945:973 N-N-linked isoquinoline dimer 945:973 Furthermore, we reveal an unusual dual BDAC sequence leading to N-N-linked isoquinoline dimer. 27399888 3 44 theme domino 684:689 arg1 process 691:697 This catalyst-free domino process 665:697 This catalyst-free domino process 665:697 This catalyst-free domino process facilitates the double annulation with a variety of scaffold building agents via two C-N and one C-X (X = C, N, O) bond formation in a single step under uniform reaction conditions. 27399888 0 45 theme Cascade 57:63 arg1 Strategy 65:72 a Branching Double-Annulation Cascade Strategy 27:72 a Branching Double-Annulation Cascade Strategy 27:72 Scaffold Diversity through a Branching Double-Annulation Cascade Strategy: Iminium-Induced One-Pot Synthesis of Diverse Fused Tetrahydroisoquinoline Scaffolds. 27399888 2 46 theme excellent 617:625 arg1 yields 627:632 good to excellent yields 609:632 good to excellent yields 609:632 The salient features of this protocol are that it allows direct and rapid access to unprecedented diverse fused THIQ skeletons, is metal/catalyst free, has a cleaner reaction profile, provides good to excellent yields, and is a convenient approach. 27399888 2 47 theme diverse 514:520 arg1 skeletons 533:541 unprecedented diverse fused THIQ skeletons 500:541 unprecedented diverse fused THIQ skeletons 500:541 The salient features of this protocol are that it allows direct and rapid access to unprecedented diverse fused THIQ skeletons, is metal/catalyst free, has a cleaner reaction profile, provides good to excellent yields, and is a convenient approach. 27399888 3 48 theme X 801:801 arg1 O 811:811 X = C, N, O 801:811 O 811:811 This catalyst-free domino process facilitates the double annulation with a variety of scaffold building agents via two C-N and one C-X (X = C, N, O) bond formation in a single step under uniform reaction conditions. 27399888 3 48 theme X 801:801 arg1 C-X 796:798 one C-X 792:798 one C-X (X = C, N, O) 792:812 This catalyst-free domino process facilitates the double annulation with a variety of scaffold building agents via two C-N and one C-X (X = C, N, O) bond formation in a single step under uniform reaction conditions. 27399888 2 49 theme good 609:612 arg1 yields 627:632 good to excellent yields 609:632 good to excellent yields 609:632 The salient features of this protocol are that it allows direct and rapid access to unprecedented diverse fused THIQ skeletons, is metal/catalyst free, has a cleaner reaction profile, provides good to excellent yields, and is a convenient approach. 27399888 1 50 theme branching 162:170 arg1 strategy 205:212 A branching double-annulation cascade (BDAC) strategy 160:212 A branching double-annulation cascade (BDAC) strategy for diverse and complex fused THIQ scaffolds via a highly reactive iminium-induced one-pot double-cyclization sequence involving Pictect-Spengler-type cyclization 160:375 A branching double-annulation cascade (BDAC) strategy for diverse and complex fused THIQ scaffolds via a highly reactive iminium-induced one-pot double-cyclization sequence involving Pictect-Spengler-type cyclization has been developed for the first time. 27399888 0 51 theme Iminium-Induced 75:89 arg1 Synthesis 99:107 Iminium-Induced One-Pot Synthesis 75:107 Scaffold Diversity through a Branching Double-Annulation Cascade Strategy: Iminium-Induced One-Pot Synthesis of Diverse Fused Tetrahydroisoquinoline Scaffolds. 0:158 Scaffold Diversity through a Branching Double-Annulation Cascade Strategy: Iminium-Induced One-Pot Synthesis of Diverse Fused Tetrahydroisoquinoline Scaffolds. 27399888 3 52 theme double 715:720 arg1 annulation 722:731 the double annulation 711:731 the double annulation with a variety of scaffold building agents 711:774 This catalyst-free domino process facilitates the double annulation with a variety of scaffold building agents via two C-N and one C-X (X = C, N, O) bond formation in a single step under uniform reaction conditions. 27399888 0 53 dep Diversity 9:17 arg1 Synthesis 99:107 Iminium-Induced One-Pot Synthesis 75:107 Scaffold Diversity through a Branching Double-Annulation Cascade Strategy: Iminium-Induced One-Pot Synthesis of Diverse Fused Tetrahydroisoquinoline Scaffolds. 0:158 Scaffold Diversity through a Branching Double-Annulation Cascade Strategy: Iminium-Induced One-Pot Synthesis of Diverse Fused Tetrahydroisoquinoline Scaffolds. 27399888 2 54 contain has 568:570 arg2 profile 591:597 a cleaner reaction profile 572:597 a cleaner reaction profile 572:597 The salient features of this protocol are that it allows direct and rapid access to unprecedented diverse fused THIQ skeletons, is metal/catalyst free, has a cleaner reaction profile, provides good to excellent yields, and is a convenient approach. 27399888 2 54 contain has 568:570 arg1 it 463:464 it 463:464 it 463:464 The salient features of this protocol are that it allows direct and rapid access to unprecedented diverse fused THIQ skeletons, is metal/catalyst free, has a cleaner reaction profile, provides good to excellent yields, and is a convenient approach. 27399888 1 55 theme double-annulation 172:188 arg1 strategy 205:212 A branching double-annulation cascade (BDAC) strategy 160:212 A branching double-annulation cascade (BDAC) strategy for diverse and complex fused THIQ scaffolds via a highly reactive iminium-induced one-pot double-cyclization sequence involving Pictect-Spengler-type cyclization 160:375 A branching double-annulation cascade (BDAC) strategy for diverse and complex fused THIQ scaffolds via a highly reactive iminium-induced one-pot double-cyclization sequence involving Pictect-Spengler-type cyclization has been developed for the first time. 27399888 3 56 theme single 834:839 arg1 step 841:844 a single step 832:844 a single step under uniform reaction conditions 832:878 This catalyst-free domino process facilitates the double annulation with a variety of scaffold building agents via two C-N and one C-X (X = C, N, O) bond formation in a single step under uniform reaction conditions. 27399888 4 57 theme isoquinoline 956:967 arg1 dimer 969:973 N-N-linked isoquinoline dimer 945:973 N-N-linked isoquinoline dimer 945:973 Furthermore, we reveal an unusual dual BDAC sequence leading to N-N-linked isoquinoline dimer. 27399888 3 58 dep C-N 784:786 arg1 formation 819:827 bond formation 814:827 bond formation 814:827 This catalyst-free domino process facilitates the double annulation with a variety of scaffold building agents via two C-N and one C-X (X = C, N, O) bond formation in a single step under uniform reaction conditions. 27399888 3 59 theme scaffold 751:758 arg1 agents 769:774 scaffold building agents 751:774 scaffold building agents 751:774 This catalyst-free domino process facilitates the double annulation with a variety of scaffold building agents via two C-N and one C-X (X = C, N, O) bond formation in a single step under uniform reaction conditions. 27399888 1 60 theme cascade 190:196 arg1 strategy 205:212 A branching double-annulation cascade (BDAC) strategy 160:212 A branching double-annulation cascade (BDAC) strategy for diverse and complex fused THIQ scaffolds via a highly reactive iminium-induced one-pot double-cyclization sequence involving Pictect-Spengler-type cyclization 160:375 A branching double-annulation cascade (BDAC) strategy for diverse and complex fused THIQ scaffolds via a highly reactive iminium-induced one-pot double-cyclization sequence involving Pictect-Spengler-type cyclization has been developed for the first time. 27399888 3 61 theme C 805:805 arg1 O 811:811 X = C, N, O 801:811 O 811:811 This catalyst-free domino process facilitates the double annulation with a variety of scaffold building agents via two C-N and one C-X (X = C, N, O) bond formation in a single step under uniform reaction conditions. 27399888 3 61 theme C 805:805 arg1 C-X 796:798 one C-X 792:798 one C-X (X = C, N, O) 792:812 This catalyst-free domino process facilitates the double annulation with a variety of scaffold building agents via two C-N and one C-X (X = C, N, O) bond formation in a single step under uniform reaction conditions. 27032207 5 0 theme oxidative 662:670 arg1 modification 672:683 oxidative modification 662:683 oxidative modification as well as truncation of the side-chain 662:723 The results demonstrated that oxidative modification as well as truncation of the side-chain abolished epoxide hydrolase inhibition. 27032207 1 1 theme molecules 142:150 arg1 family 118:123 a family 116:123 a family of natural small molecules that effectively treat ischemic stroke 116:189 SMTPs, a family of natural small molecules that effectively treat ischemic stroke, are subject to clinical development. 27032207 1 1 theme molecules 142:150 arg1 SMTPs 109:113 SMTPs 109:113 SMTPs 109:113 SMTPs, a family of natural small molecules that effectively treat ischemic stroke, are subject to clinical development. 27032207 2 2 theme endogenous 335:344 arg1 thrombolysis 346:357 endogenous thrombolysis 335:357 endogenous thrombolysis 335:357 SMTPs enhance plasminogen activation and inhibit soluble epoxide hydrolase (sEH), leading to promotion of endogenous thrombolysis and anti-inflammation. 27032207 4 3 theme SMTPs 581:585 arg1 chain 572:576 the isoprene side- chain 553:576 the isoprene side- chain of SMTPs 553:585 Here, we investigate the yet-to-be-characterized function of the isoprene side- chain of SMTPs in sEH inhibition and cellular distribution. 27032207 6 4 theme inhibition 951:960 arg1 diminution 910:919 diminution 910:919 diminution of cellular epoxide hydrolase inhibition 910:960 The introduction of a terminal hydroxy group exceptionally unaffected epoxide hydrolase, but led to impaired cellular localization, resulting in diminution of cellular epoxide hydrolase inhibition. 27032207 7 5 theme important 1007:1015 arg1 side-chain 982:991 the isoprene side-chain 969:991 the isoprene side-chain of SMTP 969:999 Thus, the isoprene side-chain of SMTP is an important pharmacophore for epoxide hydrolase inhibition and cellular localization. 27032207 7 5 theme important 1007:1015 arg1 pharmacophore 1017:1029 an important pharmacophore 1004:1029 an important pharmacophore for epoxide hydrolase inhibition and cellular localization 1004:1088 Thus, the isoprene side-chain of SMTP is an important pharmacophore for epoxide hydrolase inhibition and cellular localization. 27032207 0 6 theme Cellular 86:93 arg1 Localization 95:106 Cellular Localization 86:106 Cellular Localization 86:106 Isoprene Side-chain of SMTP is Essential for Soluble Epoxide Hydrolase Inhibition and Cellular Localization. 27032207 6 7 theme hydrolase 941:949 arg1 inhibition 951:960 cellular epoxide hydrolase inhibition 924:960 cellular epoxide hydrolase inhibition 924:960 The introduction of a terminal hydroxy group exceptionally unaffected epoxide hydrolase, but led to impaired cellular localization, resulting in diminution of cellular epoxide hydrolase inhibition. 27032207 2 8 theme epoxide 286:292 arg1 sEH 305:307 sEH 305:307 sEH 305:307 SMTPs enhance plasminogen activation and inhibit soluble epoxide hydrolase (sEH), leading to promotion of endogenous thrombolysis and anti-inflammation. 27032207 2 8 theme epoxide 286:292 arg1 hydrolase 294:302 soluble epoxide hydrolase 278:302 soluble epoxide hydrolase (sEH) 278:308 SMTPs enhance plasminogen activation and inhibit soluble epoxide hydrolase (sEH), leading to promotion of endogenous thrombolysis and anti-inflammation. 27032207 7 9 theme SMTP 996:999 arg1 side-chain 982:991 the isoprene side-chain 969:991 the isoprene side-chain of SMTP 969:999 Thus, the isoprene side-chain of SMTP is an important pharmacophore for epoxide hydrolase inhibition and cellular localization. 27032207 7 9 theme SMTP 996:999 arg1 pharmacophore 1017:1029 an important pharmacophore 1004:1029 an important pharmacophore for epoxide hydrolase inhibition and cellular localization 1004:1088 Thus, the isoprene side-chain of SMTP is an important pharmacophore for epoxide hydrolase inhibition and cellular localization. 27032207 2 10 theme thrombolysis 346:357 arg1 promotion 322:330 promotion 322:330 promotion of endogenous thrombolysis and anti-inflammation 322:379 SMTPs enhance plasminogen activation and inhibit soluble epoxide hydrolase (sEH), leading to promotion of endogenous thrombolysis and anti-inflammation. 27032207 4 11 theme sEH 590:592 arg1 inhibition 594:603 sEH inhibition 590:603 sEH inhibition 590:603 Here, we investigate the yet-to-be-characterized function of the isoprene side- chain of SMTPs in sEH inhibition and cellular distribution. 27032207 6 12 theme epoxide 933:939 arg1 hydrolase 941:949 cellular epoxide hydrolase 924:949 cellular epoxide hydrolase inhibition 924:960 The introduction of a terminal hydroxy group exceptionally unaffected epoxide hydrolase, but led to impaired cellular localization, resulting in diminution of cellular epoxide hydrolase inhibition. 27032207 2 13 theme soluble 278:284 arg1 sEH 305:307 sEH 305:307 sEH 305:307 SMTPs enhance plasminogen activation and inhibit soluble epoxide hydrolase (sEH), leading to promotion of endogenous thrombolysis and anti-inflammation. 27032207 2 13 theme soluble 278:284 arg1 hydrolase 294:302 soluble epoxide hydrolase 278:302 soluble epoxide hydrolase (sEH) 278:308 SMTPs enhance plasminogen activation and inhibit soluble epoxide hydrolase (sEH), leading to promotion of endogenous thrombolysis and anti-inflammation. 27032207 6 14 theme cellular 924:931 arg1 hydrolase 941:949 cellular epoxide hydrolase 924:949 cellular epoxide hydrolase inhibition 924:960 The introduction of a terminal hydroxy group exceptionally unaffected epoxide hydrolase, but led to impaired cellular localization, resulting in diminution of cellular epoxide hydrolase inhibition. 27032207 6 15 theme epoxide 835:841 arg1 hydrolase 843:851 epoxide hydrolase 835:851 epoxide hydrolase 835:851 The introduction of a terminal hydroxy group exceptionally unaffected epoxide hydrolase, but led to impaired cellular localization, resulting in diminution of cellular epoxide hydrolase inhibition. 27032207 3 16 theme isoprene 443:450 arg1 side-chain 452:461 an isoprene side-chain 440:461 an isoprene side-chain 440:461 The SMTP molecule consists of atricyclic γ-lactam moiety, an isoprene side-chain, and an N-linked side-chain. 27032207 3 17 theme SMTP 386:389 arg1 molecule 391:398 The SMTP molecule 382:398 The SMTP molecule 382:398 The SMTP molecule consists of atricyclic γ-lactam moiety, an isoprene side-chain, and an N-linked side-chain. 27032207 1 18 theme ischemic 175:182 arg1 stroke 184:189 ischemic stroke 175:189 ischemic stroke 175:189 SMTPs, a family of natural small molecules that effectively treat ischemic stroke, are subject to clinical development. 27032207 0 19 theme Isoprene 0:7 arg1 Side-chain 9:18 Isoprene Side-chain 0:18 Isoprene Side-chain of SMTP 0:26 Isoprene Side-chain of SMTP is Essential for Soluble Epoxide Hydrolase Inhibition and Cellular Localization. 27032207 4 20 theme side- 566:570 arg1 chain 572:576 the isoprene side- chain 553:576 the isoprene side- chain of SMTPs 553:585 Here, we investigate the yet-to-be-characterized function of the isoprene side- chain of SMTPs in sEH inhibition and cellular distribution. 27032207 0 21 theme SMTP 23:26 arg1 Side-chain 9:18 Isoprene Side-chain 0:18 Isoprene Side-chain of SMTP 0:26 Isoprene Side-chain of SMTP is Essential for Soluble Epoxide Hydrolase Inhibition and Cellular Localization. 27032207 4 22 theme isoprene 557:564 arg1 chain 572:576 the isoprene side- chain 553:576 the isoprene side- chain of SMTPs 553:585 Here, we investigate the yet-to-be-characterized function of the isoprene side- chain of SMTPs in sEH inhibition and cellular distribution. 27032207 5 23 theme side-chain 714:723 arg1 modification 672:683 oxidative modification 662:683 oxidative modification as well as truncation of the side-chain 662:723 The results demonstrated that oxidative modification as well as truncation of the side-chain abolished epoxide hydrolase inhibition. 27032207 5 23 theme side-chain 714:723 arg1 truncation 696:705 truncation 696:705 oxidative modification as well as truncation of the side-chain 662:723 The results demonstrated that oxidative modification as well as truncation of the side-chain abolished epoxide hydrolase inhibition. 27032207 6 24 theme group 804:808 arg1 introduction 769:780 The introduction 765:780 The introduction of a terminal hydroxy group 765:808 The introduction of a terminal hydroxy group exceptionally unaffected epoxide hydrolase, but led to impaired cellular localization, resulting in diminution of cellular epoxide hydrolase inhibition. 27032207 4 25 from function 541:548 arg1 inhibition 594:603 sEH inhibition 590:603 sEH inhibition 590:603 Here, we investigate the yet-to-be-characterized function of the isoprene side- chain of SMTPs in sEH inhibition and cellular distribution. 27032207 4 25 from function 541:548 arg1 distribution 618:629 cellular distribution 609:629 cellular distribution 609:629 Here, we investigate the yet-to-be-characterized function of the isoprene side- chain of SMTPs in sEH inhibition and cellular distribution. 27032207 4 26 theme cellular 609:616 arg1 distribution 618:629 cellular distribution 609:629 cellular distribution 609:629 Here, we investigate the yet-to-be-characterized function of the isoprene side- chain of SMTPs in sEH inhibition and cellular distribution. 27032207 1 27 theme natural 128:134 arg1 molecules 142:150 natural small molecules 128:150 natural small molecules 128:150 SMTPs, a family of natural small molecules that effectively treat ischemic stroke, are subject to clinical development. 27032207 3 28 theme atricyclic 412:421 arg1 moiety 432:437 atricyclic γ-lactam moiety 412:437 atricyclic γ-lactam moiety 412:437 The SMTP molecule consists of atricyclic γ-lactam moiety, an isoprene side-chain, and an N-linked side-chain. 27032207 4 29 theme chain 572:576 arg1 function 541:548 the yet-to-be-characterized function 513:548 the yet-to-be-characterized function of the isoprene side- chain of SMTPs in sEH inhibition and cellular distribution 513:629 Here, we investigate the yet-to-be-characterized function of the isoprene side- chain of SMTPs in sEH inhibition and cellular distribution. 27032207 5 30 theme epoxide 735:741 arg1 inhibition 753:762 epoxide hydrolase inhibition 735:762 epoxide hydrolase inhibition 735:762 The results demonstrated that oxidative modification as well as truncation of the side-chain abolished epoxide hydrolase inhibition. 27032207 3 31 theme γ-lactam 423:430 arg1 moiety 432:437 atricyclic γ-lactam moiety 412:437 atricyclic γ-lactam moiety 412:437 The SMTP molecule consists of atricyclic γ-lactam moiety, an isoprene side-chain, and an N-linked side-chain. 27032207 5 32 theme hydrolase 743:751 arg1 inhibition 753:762 epoxide hydrolase inhibition 735:762 epoxide hydrolase inhibition 735:762 The results demonstrated that oxidative modification as well as truncation of the side-chain abolished epoxide hydrolase inhibition. 27032207 6 33 theme hydroxy 796:802 arg1 group 804:808 a terminal hydroxy group 785:808 a terminal hydroxy group 785:808 The introduction of a terminal hydroxy group exceptionally unaffected epoxide hydrolase, but led to impaired cellular localization, resulting in diminution of cellular epoxide hydrolase inhibition. 27032207 0 34 theme Soluble 45:51 arg1 Hydrolase 61:69 Soluble Epoxide Hydrolase 45:69 Soluble Epoxide Hydrolase Inhibition 45:80 Isoprene Side-chain of SMTP is Essential for Soluble Epoxide Hydrolase Inhibition and Cellular Localization. 27032207 4 35 theme yet-to-be-characterized 517:539 arg1 function 541:548 the yet-to-be-characterized function 513:548 the yet-to-be-characterized function of the isoprene side- chain of SMTPs in sEH inhibition and cellular distribution 513:629 Here, we investigate the yet-to-be-characterized function of the isoprene side- chain of SMTPs in sEH inhibition and cellular distribution. 27032207 3 36 link N-linked 471:478 arg1 side-chain 480:489 an N-linked side-chain 468:489 an N-linked side-chain 468:489 The SMTP molecule consists of atricyclic γ-lactam moiety, an isoprene side-chain, and an N-linked side-chain. 27032207 6 37 theme terminal 787:794 arg1 group 804:808 a terminal hydroxy group 785:808 a terminal hydroxy group 785:808 The introduction of a terminal hydroxy group exceptionally unaffected epoxide hydrolase, but led to impaired cellular localization, resulting in diminution of cellular epoxide hydrolase inhibition. 27032207 7 38 theme isoprene 973:980 arg1 side-chain 982:991 the isoprene side-chain 969:991 the isoprene side-chain of SMTP 969:999 Thus, the isoprene side-chain of SMTP is an important pharmacophore for epoxide hydrolase inhibition and cellular localization. 27032207 7 38 theme isoprene 973:980 arg1 pharmacophore 1017:1029 an important pharmacophore 1004:1029 an important pharmacophore for epoxide hydrolase inhibition and cellular localization 1004:1088 Thus, the isoprene side-chain of SMTP is an important pharmacophore for epoxide hydrolase inhibition and cellular localization. 27032207 6 39 theme cellular 874:881 arg1 localization 883:894 impaired cellular localization 865:894 impaired cellular localization 865:894 The introduction of a terminal hydroxy group exceptionally unaffected epoxide hydrolase, but led to impaired cellular localization, resulting in diminution of cellular epoxide hydrolase inhibition. 27032207 3 40 theme N-linked 471:478 arg1 side-chain 480:489 an N-linked side-chain 468:489 an N-linked side-chain 468:489 The SMTP molecule consists of atricyclic γ-lactam moiety, an isoprene side-chain, and an N-linked side-chain. 27032207 1 41 theme clinical 207:214 arg1 development 216:226 clinical development 207:226 clinical development 207:226 SMTPs, a family of natural small molecules that effectively treat ischemic stroke, are subject to clinical development. 27032207 6 42 theme impaired 865:872 arg1 localization 883:894 impaired cellular localization 865:894 impaired cellular localization 865:894 The introduction of a terminal hydroxy group exceptionally unaffected epoxide hydrolase, but led to impaired cellular localization, resulting in diminution of cellular epoxide hydrolase inhibition. 27032207 7 43 theme cellular 1068:1075 arg1 localization 1077:1088 cellular localization 1068:1088 cellular localization 1068:1088 Thus, the isoprene side-chain of SMTP is an important pharmacophore for epoxide hydrolase inhibition and cellular localization. 27032207 7 44 theme epoxide 1035:1041 arg1 hydrolase 1043:1051 epoxide hydrolase 1035:1051 epoxide hydrolase inhibition 1035:1062 Thus, the isoprene side-chain of SMTP is an important pharmacophore for epoxide hydrolase inhibition and cellular localization. 27032207 0 45 theme Hydrolase 61:69 arg1 Inhibition 71:80 Soluble Epoxide Hydrolase Inhibition 45:80 Soluble Epoxide Hydrolase Inhibition 45:80 Isoprene Side-chain of SMTP is Essential for Soluble Epoxide Hydrolase Inhibition and Cellular Localization. 27032207 2 46 theme plasminogen 243:253 arg1 activation 255:264 plasminogen activation 243:264 plasminogen activation 243:264 SMTPs enhance plasminogen activation and inhibit soluble epoxide hydrolase (sEH), leading to promotion of endogenous thrombolysis and anti-inflammation. 27032207 7 47 theme hydrolase 1043:1051 arg1 inhibition 1053:1062 epoxide hydrolase inhibition 1035:1062 epoxide hydrolase inhibition 1035:1062 Thus, the isoprene side-chain of SMTP is an important pharmacophore for epoxide hydrolase inhibition and cellular localization. 27032207 2 48 theme anti-inflammation 363:379 arg1 promotion 322:330 promotion 322:330 promotion of endogenous thrombolysis and anti-inflammation 322:379 SMTPs enhance plasminogen activation and inhibit soluble epoxide hydrolase (sEH), leading to promotion of endogenous thrombolysis and anti-inflammation. 27032207 0 49 theme Epoxide 53:59 arg1 Hydrolase 61:69 Soluble Epoxide Hydrolase 45:69 Soluble Epoxide Hydrolase Inhibition 45:80 Isoprene Side-chain of SMTP is Essential for Soluble Epoxide Hydrolase Inhibition and Cellular Localization. 27032207 1 50 theme small 136:140 arg1 molecules 142:150 natural small molecules 128:150 natural small molecules 128:150 SMTPs, a family of natural small molecules that effectively treat ischemic stroke, are subject to clinical development. 29213185 8 0 theme prospective 1628:1638 arg1 directions 1640:1649 prospective directions 1628:1649 prospective directions for manipulating an increased content of fucoidan in a cultivation scenario 1628:1725 The ambiguous response to single environmental factors complicates prospective directions for manipulating an increased content of fucoidan in a cultivation scenario and emphasizes the need for knowledge on performance of local kelp ecotypes. 29213185 2 1 from industries 362:371 arg1 interest 322:329 increasing interest 311:329 increasing interest from the medico-pharmaceutical industries 311:371 The bioactive properties of fucoidans attract increasing interest from the medico-pharmaceutical industries and may drive an increase in demand of brown algae biomass. 29213185 7 2 theme digitata 1391:1398 arg1 latissima 1411:1419 L. digitata (11%) > S. latissima 1388:1419 L. digitata (11%) > S. latissima (6%) 1388:1424 The results demonstrated that (1) seasonal variation alters the fucoidan content by a factor of 2-2.6; (2) interspecific differences exist in the concentrations of crude fucoidan (% of dry matter): L. digitata (11%) > S. latissima (6%); and (3) the effects of single environmental factors were not consistent between species or between different conspecific populations. 29213185 7 2 theme digitata 1391:1398 arg1 % 1423:1423 6% 1422:1423 6% 1422:1423 The results demonstrated that (1) seasonal variation alters the fucoidan content by a factor of 2-2.6; (2) interspecific differences exist in the concentrations of crude fucoidan (% of dry matter): L. digitata (11%) > S. latissima (6%); and (3) the effects of single environmental factors were not consistent between species or between different conspecific populations. 29213185 4 3 theme fucoidans 626:634 arg1 yields 616:621 high yields 611:621 high yields of fucoidans 611:634 To cultivate and harvest kelps with high yields of fucoidans, knowledge is needed on seasonal variation and impact of environmental conditions on the fucoidan content of brown algae. 29213185 8 4 theme increased 1671:1679 arg1 content 1681:1687 an increased content 1668:1687 an increased content of fucoidan in a cultivation scenario 1668:1725 The ambiguous response to single environmental factors complicates prospective directions for manipulating an increased content of fucoidan in a cultivation scenario and emphasizes the need for knowledge on performance of local kelp ecotypes. 29213185 7 5 theme  > S. 1405:1409 arg1 latissima 1411:1419 L. digitata (11%) > S. latissima 1388:1419 L. digitata (11%) > S. latissima (6%) 1388:1424 The results demonstrated that (1) seasonal variation alters the fucoidan content by a factor of 2-2.6; (2) interspecific differences exist in the concentrations of crude fucoidan (% of dry matter): L. digitata (11%) > S. latissima (6%); and (3) the effects of single environmental factors were not consistent between species or between different conspecific populations. 29213185 7 5 theme  > S. 1405:1409 arg1 % 1423:1423 6% 1422:1423 6% 1422:1423 The results demonstrated that (1) seasonal variation alters the fucoidan content by a factor of 2-2.6; (2) interspecific differences exist in the concentrations of crude fucoidan (% of dry matter): L. digitata (11%) > S. latissima (6%); and (3) the effects of single environmental factors were not consistent between species or between different conspecific populations. 29213185 6 6 theme factors 1181:1187 arg1 effects 1159:1165 the effects 1155:1165 the effects of the single factors 1155:1187 In addition, laboratory experiments were carried out isolating the effects of the single factors. 29213185 0 7 theme Crude 0:4 arg1 content 15:21 Crude fucoidan content 0:21 Crude fucoidan content in two North Atlantic kelp species, Saccharina latissima and Laminaria digitata-seasonal variation 0:120 Crude fucoidan content in two North Atlantic kelp species, Saccharina latissima and Laminaria digitata-seasonal variation and impact of environmental factors. 29213185 7 8 dep fucoidan 1360:1367 arg1 matter 1379:1384 dry matter 1375:1384 dry matter 1375:1384 The results demonstrated that (1) seasonal variation alters the fucoidan content by a factor of 2-2.6; (2) interspecific differences exist in the concentrations of crude fucoidan (% of dry matter): L. digitata (11%) > S. latissima (6%); and (3) the effects of single environmental factors were not consistent between species or between different conspecific populations. 29213185 7 8 dep fucoidan 1360:1367 arg1 % 1370:1370 % 1370:1370 % of dry matter 1370:1384 The results demonstrated that (1) seasonal variation alters the fucoidan content by a factor of 2-2.6; (2) interspecific differences exist in the concentrations of crude fucoidan (% of dry matter): L. digitata (11%) > S. latissima (6%); and (3) the effects of single environmental factors were not consistent between species or between different conspecific populations. 29213185 7 9 theme matter 1379:1384 arg1 matter 1379:1384 dry matter 1375:1384 dry matter 1375:1384 The results demonstrated that (1) seasonal variation alters the fucoidan content by a factor of 2-2.6; (2) interspecific differences exist in the concentrations of crude fucoidan (% of dry matter): L. digitata (11%) > S. latissima (6%); and (3) the effects of single environmental factors were not consistent between species or between different conspecific populations. 29213185 7 9 theme matter 1379:1384 arg1 % 1370:1370 % 1370:1370 % of dry matter 1370:1384 The results demonstrated that (1) seasonal variation alters the fucoidan content by a factor of 2-2.6; (2) interspecific differences exist in the concentrations of crude fucoidan (% of dry matter): L. digitata (11%) > S. latissima (6%); and (3) the effects of single environmental factors were not consistent between species or between different conspecific populations. 29213185 4 10 theme conditions 707:716 arg1 variation 669:677 seasonal variation 660:677 seasonal variation 660:677 To cultivate and harvest kelps with high yields of fucoidans, knowledge is needed on seasonal variation and impact of environmental conditions on the fucoidan content of brown algae. 29213185 4 10 theme conditions 707:716 arg1 impact 683:688 impact 683:688 impact of environmental conditions on the fucoidan content of brown algae 683:755 To cultivate and harvest kelps with high yields of fucoidans, knowledge is needed on seasonal variation and impact of environmental conditions on the fucoidan content of brown algae. 29213185 4 11 theme seasonal 660:667 arg1 variation 669:677 seasonal variation 660:677 seasonal variation 660:677 To cultivate and harvest kelps with high yields of fucoidans, knowledge is needed on seasonal variation and impact of environmental conditions on the fucoidan content of brown algae. 29213185 5 12 from Hanstholm 1037:1045 arg1 year 1029:1032 a full year 1022:1032 a full year at Hanstholm in the North Sea and Aarhus in the Kattegat 1022:1089 The relations between the fucoidan content and key environmental factors (irradiance, nutrient availability, salinity and exposure) were examined by sampling natural populations of the common North Atlantic kelps, Saccharina latissima and Laminaria digitata, over a full year at Hanstholm in the North Sea and Aarhus in the Kattegat. 29213185 5 13 theme fucoidan 784:791 arg1 content 793:799 the fucoidan content 780:799 the fucoidan content 780:799 The relations between the fucoidan content and key environmental factors (irradiance, nutrient availability, salinity and exposure) were examined by sampling natural populations of the common North Atlantic kelps, Saccharina latissima and Laminaria digitata, over a full year at Hanstholm in the North Sea and Aarhus in the Kattegat. 29213185 1 14 theme cell 238:241 arg1 walls 243:247 the cell walls 234:247 the cell walls of brown algae 234:262 Fucoidans are sulphated fucose-rich polysaccharides predominantly found in the cell walls of brown algae. 29213185 7 15 theme different 1526:1534 arg1 populations 1548:1558 different conspecific populations 1526:1558 different conspecific populations 1526:1558 The results demonstrated that (1) seasonal variation alters the fucoidan content by a factor of 2-2.6; (2) interspecific differences exist in the concentrations of crude fucoidan (% of dry matter): L. digitata (11%) > S. latissima (6%); and (3) the effects of single environmental factors were not consistent between species or between different conspecific populations. 29213185 7 16 theme crude 1354:1358 arg1 fucoidan 1360:1367 crude fucoidan 1354:1367 crude fucoidan (% of dry matter) 1354:1385 The results demonstrated that (1) seasonal variation alters the fucoidan content by a factor of 2-2.6; (2) interspecific differences exist in the concentrations of crude fucoidan (% of dry matter): L. digitata (11%) > S. latissima (6%); and (3) the effects of single environmental factors were not consistent between species or between different conspecific populations. 29213185 4 17 theme brown 745:749 arg1 algae 751:755 brown algae 745:755 brown algae 745:755 To cultivate and harvest kelps with high yields of fucoidans, knowledge is needed on seasonal variation and impact of environmental conditions on the fucoidan content of brown algae. 29213185 0 18 theme factors 150:156 arg1 content 15:21 Crude fucoidan content 0:21 Crude fucoidan content in two North Atlantic kelp species, Saccharina latissima and Laminaria digitata-seasonal variation 0:120 Crude fucoidan content in two North Atlantic kelp species, Saccharina latissima and Laminaria digitata-seasonal variation and impact of environmental factors. 29213185 0 18 theme factors 150:156 arg1 impact 126:131 impact 126:131 impact of environmental factors 126:156 Crude fucoidan content in two North Atlantic kelp species, Saccharina latissima and Laminaria digitata-seasonal variation and impact of environmental factors. 29213185 5 19 theme North 950:954 arg1 latissima 983:991 Saccharina latissima 972:991 Saccharina latissima 972:991 The relations between the fucoidan content and key environmental factors (irradiance, nutrient availability, salinity and exposure) were examined by sampling natural populations of the common North Atlantic kelps, Saccharina latissima and Laminaria digitata, over a full year at Hanstholm in the North Sea and Aarhus in the Kattegat. 29213185 5 19 theme North 950:954 arg1 digitata 1007:1014 Laminaria digitata 997:1014 Laminaria digitata 997:1014 The relations between the fucoidan content and key environmental factors (irradiance, nutrient availability, salinity and exposure) were examined by sampling natural populations of the common North Atlantic kelps, Saccharina latissima and Laminaria digitata, over a full year at Hanstholm in the North Sea and Aarhus in the Kattegat. 29213185 5 19 theme North 950:954 arg1 kelps 965:969 the common North Atlantic kelps 939:969 the common North Atlantic kelps 939:969 The relations between the fucoidan content and key environmental factors (irradiance, nutrient availability, salinity and exposure) were examined by sampling natural populations of the common North Atlantic kelps, Saccharina latissima and Laminaria digitata, over a full year at Hanstholm in the North Sea and Aarhus in the Kattegat. 29213185 8 20 from knowledge 1755:1763 arg1 performance 1768:1778 performance 1768:1778 performance of local kelp ecotypes 1768:1801 The ambiguous response to single environmental factors complicates prospective directions for manipulating an increased content of fucoidan in a cultivation scenario and emphasizes the need for knowledge on performance of local kelp ecotypes. 29213185 2 21 theme bioactive 269:277 arg1 properties 279:288 The bioactive properties 265:288 The bioactive properties of fucoidans 265:301 The bioactive properties of fucoidans attract increasing interest from the medico-pharmaceutical industries and may drive an increase in demand of brown algae biomass. 29213185 5 22 theme kelps 965:969 arg1 populations 924:934 natural populations 916:934 natural populations of the common North Atlantic kelps, Saccharina latissima and Laminaria digitata, 916:1015 The relations between the fucoidan content and key environmental factors (irradiance, nutrient availability, salinity and exposure) were examined by sampling natural populations of the common North Atlantic kelps, Saccharina latissima and Laminaria digitata, over a full year at Hanstholm in the North Sea and Aarhus in the Kattegat. 29213185 4 23 dep cultivate 578:586 arg1 kelps 600:604 kelps 600:604 kelps 600:604 To cultivate and harvest kelps with high yields of fucoidans, knowledge is needed on seasonal variation and impact of environmental conditions on the fucoidan content of brown algae. 29213185 0 24 from content 15:21 arg1 species 50:56 two North Atlantic kelp species 26:56 two North Atlantic kelp species 26:56 Crude fucoidan content in two North Atlantic kelp species, Saccharina latissima and Laminaria digitata-seasonal variation and impact of environmental factors. 29213185 0 24 from content 15:21 arg1 latissima 70:78 Saccharina latissima 59:78 Saccharina latissima 59:78 Crude fucoidan content in two North Atlantic kelp species, Saccharina latissima and Laminaria digitata-seasonal variation and impact of environmental factors. 29213185 0 24 from content 15:21 arg1 variation 112:120 Laminaria digitata-seasonal variation 84:120 Laminaria digitata-seasonal variation 84:120 Crude fucoidan content in two North Atlantic kelp species, Saccharina latissima and Laminaria digitata-seasonal variation and impact of environmental factors. 29213185 0 25 theme Saccharina 59:68 arg1 species 50:56 two North Atlantic kelp species 26:56 two North Atlantic kelp species 26:56 Crude fucoidan content in two North Atlantic kelp species, Saccharina latissima and Laminaria digitata-seasonal variation and impact of environmental factors. 29213185 0 25 theme Saccharina 59:68 arg1 latissima 70:78 Saccharina latissima 59:78 Saccharina latissima 59:78 Crude fucoidan content in two North Atlantic kelp species, Saccharina latissima and Laminaria digitata-seasonal variation and impact of environmental factors. 29213185 7 26 theme factors 1471:1477 arg1 fucoidan 1360:1367 crude fucoidan 1354:1367 crude fucoidan (% of dry matter) 1354:1385 The results demonstrated that (1) seasonal variation alters the fucoidan content by a factor of 2-2.6; (2) interspecific differences exist in the concentrations of crude fucoidan (% of dry matter): L. digitata (11%) > S. latissima (6%); and (3) the effects of single environmental factors were not consistent between species or between different conspecific populations. 29213185 7 26 theme factors 1471:1477 arg1 % 1423:1423 6% 1422:1423 6% 1422:1423 The results demonstrated that (1) seasonal variation alters the fucoidan content by a factor of 2-2.6; (2) interspecific differences exist in the concentrations of crude fucoidan (% of dry matter): L. digitata (11%) > S. latissima (6%); and (3) the effects of single environmental factors were not consistent between species or between different conspecific populations. 29213185 7 26 theme factors 1471:1477 arg1 latissima 1411:1419 L. digitata (11%) > S. latissima 1388:1419 L. digitata (11%) > S. latissima (6%) 1388:1424 The results demonstrated that (1) seasonal variation alters the fucoidan content by a factor of 2-2.6; (2) interspecific differences exist in the concentrations of crude fucoidan (% of dry matter): L. digitata (11%) > S. latissima (6%); and (3) the effects of single environmental factors were not consistent between species or between different conspecific populations. 29213185 7 26 theme factors 1471:1477 arg1 effects 1439:1445 the effects 1435:1445 (3) the effects of single environmental factors 1431:1477 The results demonstrated that (1) seasonal variation alters the fucoidan content by a factor of 2-2.6; (2) interspecific differences exist in the concentrations of crude fucoidan (% of dry matter): L. digitata (11%) > S. latissima (6%); and (3) the effects of single environmental factors were not consistent between species or between different conspecific populations. 29213185 7 27 theme single 1450:1455 arg1 factors 1471:1477 single environmental factors 1450:1477 single environmental factors 1450:1477 The results demonstrated that (1) seasonal variation alters the fucoidan content by a factor of 2-2.6; (2) interspecific differences exist in the concentrations of crude fucoidan (% of dry matter): L. digitata (11%) > S. latissima (6%); and (3) the effects of single environmental factors were not consistent between species or between different conspecific populations. 29213185 0 28 theme digitata-seasonal 94:110 arg1 species 50:56 two North Atlantic kelp species 26:56 two North Atlantic kelp species 26:56 Crude fucoidan content in two North Atlantic kelp species, Saccharina latissima and Laminaria digitata-seasonal variation and impact of environmental factors. 29213185 0 28 theme digitata-seasonal 94:110 arg1 variation 112:120 Laminaria digitata-seasonal variation 84:120 Laminaria digitata-seasonal variation 84:120 Crude fucoidan content in two North Atlantic kelp species, Saccharina latissima and Laminaria digitata-seasonal variation and impact of environmental factors. 29213185 0 29 theme North 30:34 arg1 species 50:56 two North Atlantic kelp species 26:56 two North Atlantic kelp species 26:56 Crude fucoidan content in two North Atlantic kelp species, Saccharina latissima and Laminaria digitata-seasonal variation and impact of environmental factors. 29213185 0 29 theme North 30:34 arg1 latissima 70:78 Saccharina latissima 59:78 Saccharina latissima 59:78 Crude fucoidan content in two North Atlantic kelp species, Saccharina latissima and Laminaria digitata-seasonal variation and impact of environmental factors. 29213185 0 29 theme North 30:34 arg1 variation 112:120 Laminaria digitata-seasonal variation 84:120 Laminaria digitata-seasonal variation 84:120 Crude fucoidan content in two North Atlantic kelp species, Saccharina latissima and Laminaria digitata-seasonal variation and impact of environmental factors. 29213185 8 30 theme local 1783:1787 arg1 ecotypes 1794:1801 local kelp ecotypes 1783:1801 local kelp ecotypes 1783:1801 The ambiguous response to single environmental factors complicates prospective directions for manipulating an increased content of fucoidan in a cultivation scenario and emphasizes the need for knowledge on performance of local kelp ecotypes. 29213185 7 31 theme seasonal 1224:1231 arg1 variation 1233:1241 seasonal variation 1224:1241 seasonal variation 1224:1241 The results demonstrated that (1) seasonal variation alters the fucoidan content by a factor of 2-2.6; (2) interspecific differences exist in the concentrations of crude fucoidan (% of dry matter): L. digitata (11%) > S. latissima (6%); and (3) the effects of single environmental factors were not consistent between species or between different conspecific populations. 29213185 2 32 theme brown 412:416 arg1 algae 418:422 brown algae biomass 412:430 brown algae biomass 412:430 The bioactive properties of fucoidans attract increasing interest from the medico-pharmaceutical industries and may drive an increase in demand of brown algae biomass. 29213185 5 33 theme nutrient 844:851 arg1 availability 853:864 nutrient availability 844:864 nutrient availability 844:864 The relations between the fucoidan content and key environmental factors (irradiance, nutrient availability, salinity and exposure) were examined by sampling natural populations of the common North Atlantic kelps, Saccharina latissima and Laminaria digitata, over a full year at Hanstholm in the North Sea and Aarhus in the Kattegat. 29213185 5 33 theme nutrient 844:851 arg1 factors 823:829 key environmental factors 805:829 key environmental factors (irradiance, nutrient availability, salinity and exposure) 805:888 The relations between the fucoidan content and key environmental factors (irradiance, nutrient availability, salinity and exposure) were examined by sampling natural populations of the common North Atlantic kelps, Saccharina latissima and Laminaria digitata, over a full year at Hanstholm in the North Sea and Aarhus in the Kattegat. 29213185 8 34 theme ecotypes 1794:1801 arg1 performance 1768:1778 performance 1768:1778 performance of local kelp ecotypes 1768:1801 The ambiguous response to single environmental factors complicates prospective directions for manipulating an increased content of fucoidan in a cultivation scenario and emphasizes the need for knowledge on performance of local kelp ecotypes. 29213185 7 35 theme interspecific 1297:1309 arg1 differences 1311:1321 interspecific differences 1297:1321 interspecific differences 1297:1321 The results demonstrated that (1) seasonal variation alters the fucoidan content by a factor of 2-2.6; (2) interspecific differences exist in the concentrations of crude fucoidan (% of dry matter): L. digitata (11%) > S. latissima (6%); and (3) the effects of single environmental factors were not consistent between species or between different conspecific populations. 29213185 4 36 with harvest 592:598 arg1 yields 616:621 high yields 611:621 high yields of fucoidans 611:634 To cultivate and harvest kelps with high yields of fucoidans, knowledge is needed on seasonal variation and impact of environmental conditions on the fucoidan content of brown algae. 29213185 3 37 theme brown 475:479 arg1 algae 481:485 brown algae 475:485 brown algae 475:485 In nature, the biochemical composition of brown algae displays a seasonal fluctuation driven by environmental factors and endogenous rhythms. 29213185 0 38 theme Atlantic 36:43 arg1 species 50:56 two North Atlantic kelp species 26:56 two North Atlantic kelp species 26:56 Crude fucoidan content in two North Atlantic kelp species, Saccharina latissima and Laminaria digitata-seasonal variation and impact of environmental factors. 29213185 0 38 theme Atlantic 36:43 arg1 latissima 70:78 Saccharina latissima 59:78 Saccharina latissima 59:78 Crude fucoidan content in two North Atlantic kelp species, Saccharina latissima and Laminaria digitata-seasonal variation and impact of environmental factors. 29213185 0 38 theme Atlantic 36:43 arg1 variation 112:120 Laminaria digitata-seasonal variation 84:120 Laminaria digitata-seasonal variation 84:120 Crude fucoidan content in two North Atlantic kelp species, Saccharina latissima and Laminaria digitata-seasonal variation and impact of environmental factors. 29213185 7 39 dep exist 1323:1327 arg1 2 1294:1294 2 1294:1294 2 1294:1294 The results demonstrated that (1) seasonal variation alters the fucoidan content by a factor of 2-2.6; (2) interspecific differences exist in the concentrations of crude fucoidan (% of dry matter): L. digitata (11%) > S. latissima (6%); and (3) the effects of single environmental factors were not consistent between species or between different conspecific populations. 29213185 3 40 theme seasonal 498:505 arg1 fluctuation 507:517 a seasonal fluctuation 496:517 a seasonal fluctuation driven by environmental factors and endogenous rhythms 496:572 In nature, the biochemical composition of brown algae displays a seasonal fluctuation driven by environmental factors and endogenous rhythms. 29213185 8 41 theme ambiguous 1565:1573 arg1 response 1575:1582 The ambiguous response 1561:1582 The ambiguous response to single environmental factors 1561:1614 The ambiguous response to single environmental factors complicates prospective directions for manipulating an increased content of fucoidan in a cultivation scenario and emphasizes the need for knowledge on performance of local kelp ecotypes. 29213185 5 42 theme full 1024:1027 arg1 year 1029:1032 a full year 1022:1032 a full year at Hanstholm in the North Sea and Aarhus in the Kattegat 1022:1089 The relations between the fucoidan content and key environmental factors (irradiance, nutrient availability, salinity and exposure) were examined by sampling natural populations of the common North Atlantic kelps, Saccharina latissima and Laminaria digitata, over a full year at Hanstholm in the North Sea and Aarhus in the Kattegat. 29213185 8 43 from content 1681:1687 arg1 scenario 1718:1725 a cultivation scenario 1704:1725 a cultivation scenario 1704:1725 The ambiguous response to single environmental factors complicates prospective directions for manipulating an increased content of fucoidan in a cultivation scenario and emphasizes the need for knowledge on performance of local kelp ecotypes. 29213185 1 44 theme fucose-rich 183:193 arg1 polysaccharides 195:209 sulphated fucose-rich polysaccharides 173:209 sulphated fucose-rich polysaccharides predominantly found in the cell walls of brown algae 173:262 Fucoidans are sulphated fucose-rich polysaccharides predominantly found in the cell walls of brown algae. 29213185 1 44 theme fucose-rich 183:193 arg1 Fucoidans 159:167 Fucoidans 159:167 Fucoidans 159:167 Fucoidans are sulphated fucose-rich polysaccharides predominantly found in the cell walls of brown algae. 29213185 1 45 theme brown 252:256 arg1 algae 258:262 brown algae 252:262 brown algae 252:262 Fucoidans are sulphated fucose-rich polysaccharides predominantly found in the cell walls of brown algae. 29213185 6 46 theme laboratory 1105:1114 arg1 experiments 1116:1126 laboratory experiments 1105:1126 laboratory experiments 1105:1126 In addition, laboratory experiments were carried out isolating the effects of the single factors. 29213185 3 47 theme environmental 529:541 arg1 factors 543:549 environmental factors 529:549 environmental factors 529:549 In nature, the biochemical composition of brown algae displays a seasonal fluctuation driven by environmental factors and endogenous rhythms. 29213185 8 48 theme environmental 1594:1606 arg1 factors 1608:1614 single environmental factors 1587:1614 single environmental factors 1587:1614 The ambiguous response to single environmental factors complicates prospective directions for manipulating an increased content of fucoidan in a cultivation scenario and emphasizes the need for knowledge on performance of local kelp ecotypes. 29213185 1 49 theme algae 258:262 arg1 walls 243:247 the cell walls 234:247 the cell walls of brown algae 234:262 Fucoidans are sulphated fucose-rich polysaccharides predominantly found in the cell walls of brown algae. 29213185 7 50 theme latissima 1411:1419 arg1 concentrations 1336:1349 the concentrations 1332:1349 the concentrations of crude fucoidan (% of dry matter): L. digitata (11%) > S. latissima (6%); and (3) the effects of single environmental factors 1332:1477 The results demonstrated that (1) seasonal variation alters the fucoidan content by a factor of 2-2.6; (2) interspecific differences exist in the concentrations of crude fucoidan (% of dry matter): L. digitata (11%) > S. latissima (6%); and (3) the effects of single environmental factors were not consistent between species or between different conspecific populations. 29213185 7 50 theme latissima 1411:1419 arg1 consistent 1488:1497 consistent 1488:1497 consistent 1488:1497 The results demonstrated that (1) seasonal variation alters the fucoidan content by a factor of 2-2.6; (2) interspecific differences exist in the concentrations of crude fucoidan (% of dry matter): L. digitata (11%) > S. latissima (6%); and (3) the effects of single environmental factors were not consistent between species or between different conspecific populations. 29213185 4 51 theme high 611:614 arg1 yields 616:621 high yields 611:621 high yields of fucoidans 611:634 To cultivate and harvest kelps with high yields of fucoidans, knowledge is needed on seasonal variation and impact of environmental conditions on the fucoidan content of brown algae. 29213185 2 52 theme increasing 311:320 arg1 interest 322:329 increasing interest 311:329 increasing interest from the medico-pharmaceutical industries 311:371 The bioactive properties of fucoidans attract increasing interest from the medico-pharmaceutical industries and may drive an increase in demand of brown algae biomass. 29213185 2 53 theme medico-pharmaceutical 340:360 arg1 industries 362:371 the medico-pharmaceutical industries 336:371 the medico-pharmaceutical industries 336:371 The bioactive properties of fucoidans attract increasing interest from the medico-pharmaceutical industries and may drive an increase in demand of brown algae biomass. 29213185 2 54 theme fucoidans 293:301 arg1 properties 279:288 The bioactive properties 265:288 The bioactive properties of fucoidans 265:301 The bioactive properties of fucoidans attract increasing interest from the medico-pharmaceutical industries and may drive an increase in demand of brown algae biomass. 29213185 1 55 theme sulphated 173:181 arg1 polysaccharides 195:209 sulphated fucose-rich polysaccharides 173:209 sulphated fucose-rich polysaccharides predominantly found in the cell walls of brown algae 173:262 Fucoidans are sulphated fucose-rich polysaccharides predominantly found in the cell walls of brown algae. 29213185 1 55 theme sulphated 173:181 arg1 Fucoidans 159:167 Fucoidans 159:167 Fucoidans 159:167 Fucoidans are sulphated fucose-rich polysaccharides predominantly found in the cell walls of brown algae. 29213185 2 56 from increase 390:397 arg1 demand 402:407 demand 402:407 demand of brown algae biomass 402:430 The bioactive properties of fucoidans attract increasing interest from the medico-pharmaceutical industries and may drive an increase in demand of brown algae biomass. 29213185 6 57 theme single 1174:1179 arg1 factors 1181:1187 the single factors 1170:1187 the single factors 1170:1187 In addition, laboratory experiments were carried out isolating the effects of the single factors. 29213185 5 58 theme key 805:807 arg1 exposure 880:887 exposure 880:887 exposure 880:887 The relations between the fucoidan content and key environmental factors (irradiance, nutrient availability, salinity and exposure) were examined by sampling natural populations of the common North Atlantic kelps, Saccharina latissima and Laminaria digitata, over a full year at Hanstholm in the North Sea and Aarhus in the Kattegat. 29213185 5 58 theme key 805:807 arg1 salinity 867:874 salinity 867:874 salinity 867:874 The relations between the fucoidan content and key environmental factors (irradiance, nutrient availability, salinity and exposure) were examined by sampling natural populations of the common North Atlantic kelps, Saccharina latissima and Laminaria digitata, over a full year at Hanstholm in the North Sea and Aarhus in the Kattegat. 29213185 5 58 theme key 805:807 arg1 irradiance 832:841 irradiance 832:841 irradiance 832:841 The relations between the fucoidan content and key environmental factors (irradiance, nutrient availability, salinity and exposure) were examined by sampling natural populations of the common North Atlantic kelps, Saccharina latissima and Laminaria digitata, over a full year at Hanstholm in the North Sea and Aarhus in the Kattegat. 29213185 5 58 theme key 805:807 arg1 availability 853:864 nutrient availability 844:864 nutrient availability 844:864 The relations between the fucoidan content and key environmental factors (irradiance, nutrient availability, salinity and exposure) were examined by sampling natural populations of the common North Atlantic kelps, Saccharina latissima and Laminaria digitata, over a full year at Hanstholm in the North Sea and Aarhus in the Kattegat. 29213185 5 58 theme key 805:807 arg1 factors 823:829 key environmental factors 805:829 key environmental factors (irradiance, nutrient availability, salinity and exposure) 805:888 The relations between the fucoidan content and key environmental factors (irradiance, nutrient availability, salinity and exposure) were examined by sampling natural populations of the common North Atlantic kelps, Saccharina latissima and Laminaria digitata, over a full year at Hanstholm in the North Sea and Aarhus in the Kattegat. 29213185 4 59 with cultivate 578:586 arg1 yields 616:621 high yields 611:621 high yields of fucoidans 611:634 To cultivate and harvest kelps with high yields of fucoidans, knowledge is needed on seasonal variation and impact of environmental conditions on the fucoidan content of brown algae. 29213185 4 60 from impact 683:688 arg1 content 734:740 the fucoidan content 721:740 the fucoidan content of brown algae 721:755 To cultivate and harvest kelps with high yields of fucoidans, knowledge is needed on seasonal variation and impact of environmental conditions on the fucoidan content of brown algae. 29213185 5 61 dep factors 823:829 arg1 exposure 880:887 exposure 880:887 exposure 880:887 The relations between the fucoidan content and key environmental factors (irradiance, nutrient availability, salinity and exposure) were examined by sampling natural populations of the common North Atlantic kelps, Saccharina latissima and Laminaria digitata, over a full year at Hanstholm in the North Sea and Aarhus in the Kattegat. 29213185 5 61 dep factors 823:829 arg1 salinity 867:874 salinity 867:874 salinity 867:874 The relations between the fucoidan content and key environmental factors (irradiance, nutrient availability, salinity and exposure) were examined by sampling natural populations of the common North Atlantic kelps, Saccharina latissima and Laminaria digitata, over a full year at Hanstholm in the North Sea and Aarhus in the Kattegat. 29213185 5 61 dep factors 823:829 arg1 irradiance 832:841 irradiance 832:841 irradiance 832:841 The relations between the fucoidan content and key environmental factors (irradiance, nutrient availability, salinity and exposure) were examined by sampling natural populations of the common North Atlantic kelps, Saccharina latissima and Laminaria digitata, over a full year at Hanstholm in the North Sea and Aarhus in the Kattegat. 29213185 5 61 dep factors 823:829 arg1 availability 853:864 nutrient availability 844:864 nutrient availability 844:864 The relations between the fucoidan content and key environmental factors (irradiance, nutrient availability, salinity and exposure) were examined by sampling natural populations of the common North Atlantic kelps, Saccharina latissima and Laminaria digitata, over a full year at Hanstholm in the North Sea and Aarhus in the Kattegat. 29213185 5 61 dep factors 823:829 arg1 factors 823:829 key environmental factors 805:829 key environmental factors (irradiance, nutrient availability, salinity and exposure) 805:888 The relations between the fucoidan content and key environmental factors (irradiance, nutrient availability, salinity and exposure) were examined by sampling natural populations of the common North Atlantic kelps, Saccharina latissima and Laminaria digitata, over a full year at Hanstholm in the North Sea and Aarhus in the Kattegat. 29213185 4 62 theme environmental 693:705 arg1 conditions 707:716 environmental conditions 693:716 environmental conditions 693:716 To cultivate and harvest kelps with high yields of fucoidans, knowledge is needed on seasonal variation and impact of environmental conditions on the fucoidan content of brown algae. 29213185 5 63 theme North 1054:1058 arg1 Sea 1060:1062 the North Sea 1050:1062 the North Sea 1050:1062 The relations between the fucoidan content and key environmental factors (irradiance, nutrient availability, salinity and exposure) were examined by sampling natural populations of the common North Atlantic kelps, Saccharina latissima and Laminaria digitata, over a full year at Hanstholm in the North Sea and Aarhus in the Kattegat. 29213185 4 64 from variation 669:677 arg1 content 734:740 the fucoidan content 721:740 the fucoidan content of brown algae 721:755 To cultivate and harvest kelps with high yields of fucoidans, knowledge is needed on seasonal variation and impact of environmental conditions on the fucoidan content of brown algae. 29213185 7 65 theme conspecific 1536:1546 arg1 populations 1548:1558 different conspecific populations 1526:1558 different conspecific populations 1526:1558 The results demonstrated that (1) seasonal variation alters the fucoidan content by a factor of 2-2.6; (2) interspecific differences exist in the concentrations of crude fucoidan (% of dry matter): L. digitata (11%) > S. latissima (6%); and (3) the effects of single environmental factors were not consistent between species or between different conspecific populations. 29213185 7 66 theme dry 1375:1377 arg1 matter 1379:1384 dry matter 1375:1384 dry matter 1375:1384 The results demonstrated that (1) seasonal variation alters the fucoidan content by a factor of 2-2.6; (2) interspecific differences exist in the concentrations of crude fucoidan (% of dry matter): L. digitata (11%) > S. latissima (6%); and (3) the effects of single environmental factors were not consistent between species or between different conspecific populations. 29213185 0 67 theme environmental 136:148 arg1 factors 150:156 environmental factors 136:156 environmental factors 136:156 Crude fucoidan content in two North Atlantic kelp species, Saccharina latissima and Laminaria digitata-seasonal variation and impact of environmental factors. 29213185 5 68 theme common 943:948 arg1 latissima 983:991 Saccharina latissima 972:991 Saccharina latissima 972:991 The relations between the fucoidan content and key environmental factors (irradiance, nutrient availability, salinity and exposure) were examined by sampling natural populations of the common North Atlantic kelps, Saccharina latissima and Laminaria digitata, over a full year at Hanstholm in the North Sea and Aarhus in the Kattegat. 29213185 5 68 theme common 943:948 arg1 digitata 1007:1014 Laminaria digitata 997:1014 Laminaria digitata 997:1014 The relations between the fucoidan content and key environmental factors (irradiance, nutrient availability, salinity and exposure) were examined by sampling natural populations of the common North Atlantic kelps, Saccharina latissima and Laminaria digitata, over a full year at Hanstholm in the North Sea and Aarhus in the Kattegat. 29213185 5 68 theme common 943:948 arg1 kelps 965:969 the common North Atlantic kelps 939:969 the common North Atlantic kelps 939:969 The relations between the fucoidan content and key environmental factors (irradiance, nutrient availability, salinity and exposure) were examined by sampling natural populations of the common North Atlantic kelps, Saccharina latissima and Laminaria digitata, over a full year at Hanstholm in the North Sea and Aarhus in the Kattegat. 29213185 7 69 theme fucoidan 1360:1367 arg1 concentrations 1336:1349 the concentrations 1332:1349 the concentrations of crude fucoidan (% of dry matter): L. digitata (11%) > S. latissima (6%); and (3) the effects of single environmental factors 1332:1477 The results demonstrated that (1) seasonal variation alters the fucoidan content by a factor of 2-2.6; (2) interspecific differences exist in the concentrations of crude fucoidan (% of dry matter): L. digitata (11%) > S. latissima (6%); and (3) the effects of single environmental factors were not consistent between species or between different conspecific populations. 29213185 7 69 theme fucoidan 1360:1367 arg1 consistent 1488:1497 consistent 1488:1497 consistent 1488:1497 The results demonstrated that (1) seasonal variation alters the fucoidan content by a factor of 2-2.6; (2) interspecific differences exist in the concentrations of crude fucoidan (% of dry matter): L. digitata (11%) > S. latissima (6%); and (3) the effects of single environmental factors were not consistent between species or between different conspecific populations. 29213185 1 70 located found 225:229 arg1 walls 243:247 the cell walls 234:247 the cell walls of brown algae 234:262 Fucoidans are sulphated fucose-rich polysaccharides predominantly found in the cell walls of brown algae. 29213185 1 70 located found 225:229 arg2 Fucoidans 159:167 Fucoidans 159:167 Fucoidans 159:167 Fucoidans are sulphated fucose-rich polysaccharides predominantly found in the cell walls of brown algae. 29213185 1 70 located found 225:229 arg2 polysaccharides 195:209 sulphated fucose-rich polysaccharides 173:209 sulphated fucose-rich polysaccharides predominantly found in the cell walls of brown algae 173:262 Fucoidans are sulphated fucose-rich polysaccharides predominantly found in the cell walls of brown algae. 29213185 8 71 theme cultivation 1706:1716 arg1 scenario 1718:1725 a cultivation scenario 1704:1725 a cultivation scenario 1704:1725 The ambiguous response to single environmental factors complicates prospective directions for manipulating an increased content of fucoidan in a cultivation scenario and emphasizes the need for knowledge on performance of local kelp ecotypes. 29213185 5 72 theme Atlantic 956:963 arg1 latissima 983:991 Saccharina latissima 972:991 Saccharina latissima 972:991 The relations between the fucoidan content and key environmental factors (irradiance, nutrient availability, salinity and exposure) were examined by sampling natural populations of the common North Atlantic kelps, Saccharina latissima and Laminaria digitata, over a full year at Hanstholm in the North Sea and Aarhus in the Kattegat. 29213185 5 72 theme Atlantic 956:963 arg1 digitata 1007:1014 Laminaria digitata 997:1014 Laminaria digitata 997:1014 The relations between the fucoidan content and key environmental factors (irradiance, nutrient availability, salinity and exposure) were examined by sampling natural populations of the common North Atlantic kelps, Saccharina latissima and Laminaria digitata, over a full year at Hanstholm in the North Sea and Aarhus in the Kattegat. 29213185 5 72 theme Atlantic 956:963 arg1 kelps 965:969 the common North Atlantic kelps 939:969 the common North Atlantic kelps 939:969 The relations between the fucoidan content and key environmental factors (irradiance, nutrient availability, salinity and exposure) were examined by sampling natural populations of the common North Atlantic kelps, Saccharina latissima and Laminaria digitata, over a full year at Hanstholm in the North Sea and Aarhus in the Kattegat. 29213185 4 73 theme algae 751:755 arg1 content 734:740 the fucoidan content 721:740 the fucoidan content of brown algae 721:755 To cultivate and harvest kelps with high yields of fucoidans, knowledge is needed on seasonal variation and impact of environmental conditions on the fucoidan content of brown algae. 29213185 5 74 from Aarhus 1068:1073 arg1 year 1029:1032 a full year 1022:1032 a full year at Hanstholm in the North Sea and Aarhus in the Kattegat 1022:1089 The relations between the fucoidan content and key environmental factors (irradiance, nutrient availability, salinity and exposure) were examined by sampling natural populations of the common North Atlantic kelps, Saccharina latissima and Laminaria digitata, over a full year at Hanstholm in the North Sea and Aarhus in the Kattegat. 29213185 5 75 theme natural 916:922 arg1 populations 924:934 natural populations 916:934 natural populations of the common North Atlantic kelps, Saccharina latissima and Laminaria digitata, 916:1015 The relations between the fucoidan content and key environmental factors (irradiance, nutrient availability, salinity and exposure) were examined by sampling natural populations of the common North Atlantic kelps, Saccharina latissima and Laminaria digitata, over a full year at Hanstholm in the North Sea and Aarhus in the Kattegat. 29213185 7 76 theme environmental 1457:1469 arg1 factors 1471:1477 single environmental factors 1450:1477 single environmental factors 1450:1477 The results demonstrated that (1) seasonal variation alters the fucoidan content by a factor of 2-2.6; (2) interspecific differences exist in the concentrations of crude fucoidan (% of dry matter): L. digitata (11%) > S. latissima (6%); and (3) the effects of single environmental factors were not consistent between species or between different conspecific populations. 29213185 4 77 theme fucoidan 725:732 arg1 content 734:740 the fucoidan content 721:740 the fucoidan content of brown algae 721:755 To cultivate and harvest kelps with high yields of fucoidans, knowledge is needed on seasonal variation and impact of environmental conditions on the fucoidan content of brown algae. 29213185 0 78 theme Laminaria 84:92 arg1 species 50:56 two North Atlantic kelp species 26:56 two North Atlantic kelp species 26:56 Crude fucoidan content in two North Atlantic kelp species, Saccharina latissima and Laminaria digitata-seasonal variation and impact of environmental factors. 29213185 0 78 theme Laminaria 84:92 arg1 variation 112:120 Laminaria digitata-seasonal variation 84:120 Laminaria digitata-seasonal variation 84:120 Crude fucoidan content in two North Atlantic kelp species, Saccharina latissima and Laminaria digitata-seasonal variation and impact of environmental factors. 29213185 8 79 theme fucoidan 1692:1699 arg1 content 1681:1687 an increased content 1668:1687 an increased content of fucoidan in a cultivation scenario 1668:1725 The ambiguous response to single environmental factors complicates prospective directions for manipulating an increased content of fucoidan in a cultivation scenario and emphasizes the need for knowledge on performance of local kelp ecotypes. 29213185 2 80 theme algae 418:422 arg1 demand 402:407 demand 402:407 demand of brown algae biomass 402:430 The bioactive properties of fucoidans attract increasing interest from the medico-pharmaceutical industries and may drive an increase in demand of brown algae biomass. 29213185 0 81 theme fucoidan 6:13 arg1 content 15:21 Crude fucoidan content 0:21 Crude fucoidan content in two North Atlantic kelp species, Saccharina latissima and Laminaria digitata-seasonal variation 0:120 Crude fucoidan content in two North Atlantic kelp species, Saccharina latissima and Laminaria digitata-seasonal variation and impact of environmental factors. 29213185 7 82 dep alters 1243:1248 arg1 1 1221:1221 1 1221:1221 1 1221:1221 The results demonstrated that (1) seasonal variation alters the fucoidan content by a factor of 2-2.6; (2) interspecific differences exist in the concentrations of crude fucoidan (% of dry matter): L. digitata (11%) > S. latissima (6%); and (3) the effects of single environmental factors were not consistent between species or between different conspecific populations. 29213185 3 83 theme biochemical 448:458 arg1 composition 460:470 the biochemical composition 444:470 the biochemical composition of brown algae 444:485 In nature, the biochemical composition of brown algae displays a seasonal fluctuation driven by environmental factors and endogenous rhythms. 29213185 8 84 theme kelp 1789:1792 arg1 ecotypes 1794:1801 local kelp ecotypes 1783:1801 local kelp ecotypes 1783:1801 The ambiguous response to single environmental factors complicates prospective directions for manipulating an increased content of fucoidan in a cultivation scenario and emphasizes the need for knowledge on performance of local kelp ecotypes. 29213185 5 85 theme environmental 809:821 arg1 exposure 880:887 exposure 880:887 exposure 880:887 The relations between the fucoidan content and key environmental factors (irradiance, nutrient availability, salinity and exposure) were examined by sampling natural populations of the common North Atlantic kelps, Saccharina latissima and Laminaria digitata, over a full year at Hanstholm in the North Sea and Aarhus in the Kattegat. 29213185 5 85 theme environmental 809:821 arg1 salinity 867:874 salinity 867:874 salinity 867:874 The relations between the fucoidan content and key environmental factors (irradiance, nutrient availability, salinity and exposure) were examined by sampling natural populations of the common North Atlantic kelps, Saccharina latissima and Laminaria digitata, over a full year at Hanstholm in the North Sea and Aarhus in the Kattegat. 29213185 5 85 theme environmental 809:821 arg1 irradiance 832:841 irradiance 832:841 irradiance 832:841 The relations between the fucoidan content and key environmental factors (irradiance, nutrient availability, salinity and exposure) were examined by sampling natural populations of the common North Atlantic kelps, Saccharina latissima and Laminaria digitata, over a full year at Hanstholm in the North Sea and Aarhus in the Kattegat. 29213185 5 85 theme environmental 809:821 arg1 availability 853:864 nutrient availability 844:864 nutrient availability 844:864 The relations between the fucoidan content and key environmental factors (irradiance, nutrient availability, salinity and exposure) were examined by sampling natural populations of the common North Atlantic kelps, Saccharina latissima and Laminaria digitata, over a full year at Hanstholm in the North Sea and Aarhus in the Kattegat. 29213185 5 85 theme environmental 809:821 arg1 factors 823:829 key environmental factors 805:829 key environmental factors (irradiance, nutrient availability, salinity and exposure) 805:888 The relations between the fucoidan content and key environmental factors (irradiance, nutrient availability, salinity and exposure) were examined by sampling natural populations of the common North Atlantic kelps, Saccharina latissima and Laminaria digitata, over a full year at Hanstholm in the North Sea and Aarhus in the Kattegat. 29213185 7 86 theme effects 1439:1445 arg1 concentrations 1336:1349 the concentrations 1332:1349 the concentrations of crude fucoidan (% of dry matter): L. digitata (11%) > S. latissima (6%); and (3) the effects of single environmental factors 1332:1477 The results demonstrated that (1) seasonal variation alters the fucoidan content by a factor of 2-2.6; (2) interspecific differences exist in the concentrations of crude fucoidan (% of dry matter): L. digitata (11%) > S. latissima (6%); and (3) the effects of single environmental factors were not consistent between species or between different conspecific populations. 29213185 7 86 theme effects 1439:1445 arg1 consistent 1488:1497 consistent 1488:1497 consistent 1488:1497 The results demonstrated that (1) seasonal variation alters the fucoidan content by a factor of 2-2.6; (2) interspecific differences exist in the concentrations of crude fucoidan (% of dry matter): L. digitata (11%) > S. latissima (6%); and (3) the effects of single environmental factors were not consistent between species or between different conspecific populations. 29213185 7 87 theme 2-2.6 1286:1290 arg1 factor 1276:1281 a factor 1274:1281 a factor of 2-2.6 1274:1290 The results demonstrated that (1) seasonal variation alters the fucoidan content by a factor of 2-2.6; (2) interspecific differences exist in the concentrations of crude fucoidan (% of dry matter): L. digitata (11%) > S. latissima (6%); and (3) the effects of single environmental factors were not consistent between species or between different conspecific populations. 29213185 3 88 theme algae 481:485 arg1 composition 460:470 the biochemical composition 444:470 the biochemical composition of brown algae 444:485 In nature, the biochemical composition of brown algae displays a seasonal fluctuation driven by environmental factors and endogenous rhythms. 29213185 0 89 theme kelp 45:48 arg1 species 50:56 two North Atlantic kelp species 26:56 two North Atlantic kelp species 26:56 Crude fucoidan content in two North Atlantic kelp species, Saccharina latissima and Laminaria digitata-seasonal variation and impact of environmental factors. 29213185 0 89 theme kelp 45:48 arg1 latissima 70:78 Saccharina latissima 59:78 Saccharina latissima 59:78 Crude fucoidan content in two North Atlantic kelp species, Saccharina latissima and Laminaria digitata-seasonal variation and impact of environmental factors. 29213185 0 89 theme kelp 45:48 arg1 variation 112:120 Laminaria digitata-seasonal variation 84:120 Laminaria digitata-seasonal variation 84:120 Crude fucoidan content in two North Atlantic kelp species, Saccharina latissima and Laminaria digitata-seasonal variation and impact of environmental factors. 29213185 8 90 theme single 1587:1592 arg1 factors 1608:1614 single environmental factors 1587:1614 single environmental factors 1587:1614 The ambiguous response to single environmental factors complicates prospective directions for manipulating an increased content of fucoidan in a cultivation scenario and emphasizes the need for knowledge on performance of local kelp ecotypes. 29213185 7 91 theme fucoidan 1254:1261 arg1 content 1263:1269 the fucoidan content 1250:1269 the fucoidan content 1250:1269 The results demonstrated that (1) seasonal variation alters the fucoidan content by a factor of 2-2.6; (2) interspecific differences exist in the concentrations of crude fucoidan (% of dry matter): L. digitata (11%) > S. latissima (6%); and (3) the effects of single environmental factors were not consistent between species or between different conspecific populations. 29213185 0 92 from impact 126:131 arg1 species 50:56 two North Atlantic kelp species 26:56 two North Atlantic kelp species 26:56 Crude fucoidan content in two North Atlantic kelp species, Saccharina latissima and Laminaria digitata-seasonal variation and impact of environmental factors. 29213185 0 92 from impact 126:131 arg1 latissima 70:78 Saccharina latissima 59:78 Saccharina latissima 59:78 Crude fucoidan content in two North Atlantic kelp species, Saccharina latissima and Laminaria digitata-seasonal variation and impact of environmental factors. 29213185 0 92 from impact 126:131 arg1 variation 112:120 Laminaria digitata-seasonal variation 84:120 Laminaria digitata-seasonal variation 84:120 Crude fucoidan content in two North Atlantic kelp species, Saccharina latissima and Laminaria digitata-seasonal variation and impact of environmental factors. 29213185 2 93 dep algae 418:422 arg1 biomass 424:430 biomass 424:430 brown algae biomass 412:430 The bioactive properties of fucoidans attract increasing interest from the medico-pharmaceutical industries and may drive an increase in demand of brown algae biomass. 29213185 3 94 theme endogenous 555:564 arg1 rhythms 566:572 endogenous rhythms 555:572 endogenous rhythms 555:572 In nature, the biochemical composition of brown algae displays a seasonal fluctuation driven by environmental factors and endogenous rhythms. 29213185 7 95 dep effects 1439:1445 arg1 3 1432:1432 3 1432:1432 3 1432:1432 The results demonstrated that (1) seasonal variation alters the fucoidan content by a factor of 2-2.6; (2) interspecific differences exist in the concentrations of crude fucoidan (% of dry matter): L. digitata (11%) > S. latissima (6%); and (3) the effects of single environmental factors were not consistent between species or between different conspecific populations. 28939605 4 0 theme columnar 841:848 arg1 gigantea 908:915 Carnegiea gigantea 898:915 Carnegiea gigantea (saguaro cactus) 898:932 Drosophila nigrospiracula is a species that is endemic to the Sonoran Desert and is restricted to decaying tissues of two giant columnar cacti, Pachycereus pringlei (cardón cactus) and Carnegiea gigantea (saguaro cactus). 28939605 4 0 theme columnar 841:848 arg1 cacti 850:854 two giant columnar cacti 831:854 two giant columnar cacti 831:854 Drosophila nigrospiracula is a species that is endemic to the Sonoran Desert and is restricted to decaying tissues of two giant columnar cacti, Pachycereus pringlei (cardón cactus) and Carnegiea gigantea (saguaro cactus). 28939605 4 0 theme columnar 841:848 arg1 pringlei 869:876 Pachycereus pringlei 857:876 Pachycereus pringlei (cardón cactus) 857:892 Drosophila nigrospiracula is a species that is endemic to the Sonoran Desert and is restricted to decaying tissues of two giant columnar cacti, Pachycereus pringlei (cardón cactus) and Carnegiea gigantea (saguaro cactus). 28939605 9 1 theme direct 1802:1807 arg1 transmission 1822:1833 direct host-to-host transmission 1802:1833 direct host-to-host transmission 1802:1833 Thus, these bacterial groups appear to be specialized to the insect gut environment, where they may colonize through direct host-to-host transmission in natural settings.IMPORTANCE Flies in the genus Drosophila have become laboratory models for microbiota research, yet the bacteria commonly used in these experiments are rarely found in wild-caught flies and instead represent bacteria also present in the food. 28939605 1 2 contain possess 120:126 arg1 animals 112:118 Almost all animals 101:118 Almost all animals 101:118 Almost all animals possess gut microbial communities, but the nature of these communities varies immensely. 28939605 1 2 contain possess 120:126 arg2 communities 142:152 gut microbial communities 128:152 gut microbial communities 128:152 Almost all animals possess gut microbial communities, but the nature of these communities varies immensely. 28939605 6 3 from flies 1181:1185 arg1 bacteria 1075:1082 The most abundant bacteria 1057:1082 The most abundant bacteria in the flies 1057:1095 The most abundant bacteria in the flies are rare or completely absent in the cactus tissue and are consistently abundant in flies from different cacti and localities. 28939605 6 3 from flies 1181:1185 arg1 rare 1101:1104 rare 1101:1104 rare 1101:1104 The most abundant bacteria in the flies are rare or completely absent in the cactus tissue and are consistently abundant in flies from different cacti and localities. 28939605 6 3 from flies 1181:1185 arg1 abundant 1169:1176 abundant 1169:1176 abundant 1169:1176 The most abundant bacteria in the flies are rare or completely absent in the cactus tissue and are consistently abundant in flies from different cacti and localities. 28939605 8 4 theme Orbales 1577:1583 arg1 species 1585:1591 Orbales species 1577:1591 Orbales species studied in bees 1577:1607 Although the functions of these bacterial groups are mostly unexplored, Orbales species studied in bees are known to break down plant polysaccharides and use the resulting sugars. 28939605 8 5 theme plant 1633:1637 arg1 polysaccharides 1639:1653 down plant polysaccharides 1628:1653 down plant polysaccharides 1628:1653 Although the functions of these bacterial groups are mostly unexplored, Orbales species studied in bees are known to break down plant polysaccharides and use the resulting sugars. 28939605 3 6 from specialist 603:612 arg1 habitat 629:635 its natural habitat 617:635 its natural habitat 617:635 We addressed whether an ecological specialist in its natural habitat has a microbiota dominated by gut specialists or by environmental bacteria. 28939605 10 7 theme natural 2254:2260 arg1 food 2262:2265 the flies' natural food 2243:2265 the flies' natural food 2243:2265 This study shows that an ecologically specialized Drosophila species possesses a distinctive microbiome, composed of bacterial types absent from the flies' natural food but widespread in other wild-caught insects. 28939605 9 8 theme natural 1838:1844 arg1 Flies 1866:1870 natural settings.IMPORTANCE Flies 1838:1870 natural settings.IMPORTANCE Flies in the genus Drosophila 1838:1894 Thus, these bacterial groups appear to be specialized to the insect gut environment, where they may colonize through direct host-to-host transmission in natural settings.IMPORTANCE Flies in the genus Drosophila have become laboratory models for microbiota research, yet the bacteria commonly used in these experiments are rarely found in wild-caught flies and instead represent bacteria also present in the food. 28939605 6 9 theme different 1192:1200 arg1 cacti 1202:1206 different cacti 1192:1206 different cacti 1192:1206 The most abundant bacteria in the flies are rare or completely absent in the cactus tissue and are consistently abundant in flies from different cacti and localities. 28939605 7 10 from surveys 1381:1387 arg1 Lepidoptera 1441:1451 Lepidoptera 1441:1451 Lepidoptera 1441:1451 Several of these fly-associated bacterial groups, such as the bacterial order Orbales and the genera Serpens and Dysgonomonas, have been identified in prior surveys of insects from the orders Hymenoptera, Coleoptera, Lepidoptera, and Diptera, including several Drosophila species. 28939605 7 10 from surveys 1381:1387 arg1 orders 1409:1414 the orders 1405:1414 the orders Hymenoptera, Coleoptera, Lepidoptera, and Diptera 1405:1464 Several of these fly-associated bacterial groups, such as the bacterial order Orbales and the genera Serpens and Dysgonomonas, have been identified in prior surveys of insects from the orders Hymenoptera, Coleoptera, Lepidoptera, and Diptera, including several Drosophila species. 28939605 7 10 from surveys 1381:1387 arg1 Coleoptera 1429:1438 Coleoptera 1429:1438 Coleoptera 1429:1438 Several of these fly-associated bacterial groups, such as the bacterial order Orbales and the genera Serpens and Dysgonomonas, have been identified in prior surveys of insects from the orders Hymenoptera, Coleoptera, Lepidoptera, and Diptera, including several Drosophila species. 28939605 7 10 from surveys 1381:1387 arg1 Diptera 1458:1464 Diptera 1458:1464 Diptera 1458:1464 Several of these fly-associated bacterial groups, such as the bacterial order Orbales and the genera Serpens and Dysgonomonas, have been identified in prior surveys of insects from the orders Hymenoptera, Coleoptera, Lepidoptera, and Diptera, including several Drosophila species. 28939605 1 11 theme communities 179:189 arg1 nature 163:168 the nature 159:168 the nature of these communities 159:189 Almost all animals possess gut microbial communities, but the nature of these communities varies immensely. 28939605 5 12 dep D. 953:954 arg1 nigrospiracula 956:969 D. nigrospiracula 953:969 the D. nigrospiracula microbiota 949:980 We found that the D. nigrospiracula microbiota differs strikingly from that of the cactus tissue on which the flies feed. 28939605 11 13 theme research 2382:2389 arg1 importance 2338:2347 the importance 2334:2347 the importance of fieldwork-informed microbiota research 2334:2389 This study highlights the importance of fieldwork-informed microbiota research. 28939605 10 14 theme absent 2231:2236 arg1 types 2225:2229 bacterial types 2215:2229 bacterial types absent from the flies' natural food but widespread in other wild-caught insects 2215:2309 This study shows that an ecologically specialized Drosophila species possesses a distinctive microbiome, composed of bacterial types absent from the flies' natural food but widespread in other wild-caught insects. 28939605 4 15 dep gigantea 908:915 arg1 cactus 926:931 saguaro cactus 918:931 saguaro cactus 918:931 Drosophila nigrospiracula is a species that is endemic to the Sonoran Desert and is restricted to decaying tissues of two giant columnar cacti, Pachycereus pringlei (cardón cactus) and Carnegiea gigantea (saguaro cactus). 28939605 9 16 theme present 2077:2083 arg1 bacteria 2063:2070 bacteria 2063:2070 bacteria also present in the food 2063:2095 Thus, these bacterial groups appear to be specialized to the insect gut environment, where they may colonize through direct host-to-host transmission in natural settings.IMPORTANCE Flies in the genus Drosophila have become laboratory models for microbiota research, yet the bacteria commonly used in these experiments are rarely found in wild-caught flies and instead represent bacteria also present in the food. 28939605 10 17 theme wild-caught 2291:2301 arg1 insects 2303:2309 other wild-caught insects 2285:2309 other wild-caught insects 2285:2309 This study shows that an ecologically specialized Drosophila species possesses a distinctive microbiome, composed of bacterial types absent from the flies' natural food but widespread in other wild-caught insects. 28939605 1 18 theme microbial 132:140 arg1 communities 142:152 gut microbial communities 128:152 gut microbial communities 128:152 Almost all animals possess gut microbial communities, but the nature of these communities varies immensely. 28939605 6 19 theme cactus 1134:1139 arg1 tissue 1141:1146 the cactus tissue 1130:1146 the cactus tissue 1130:1146 The most abundant bacteria in the flies are rare or completely absent in the cactus tissue and are consistently abundant in flies from different cacti and localities. 28939605 9 20 theme microbiota 1930:1939 arg1 research 1941:1948 microbiota research 1930:1948 microbiota research 1930:1948 Thus, these bacterial groups appear to be specialized to the insect gut environment, where they may colonize through direct host-to-host transmission in natural settings.IMPORTANCE Flies in the genus Drosophila have become laboratory models for microbiota research, yet the bacteria commonly used in these experiments are rarely found in wild-caught flies and instead represent bacteria also present in the food. 28939605 9 21 located found 2014:2018 arg1 flies 2035:2039 wild-caught flies 2023:2039 wild-caught flies 2023:2039 Thus, these bacterial groups appear to be specialized to the insect gut environment, where they may colonize through direct host-to-host transmission in natural settings.IMPORTANCE Flies in the genus Drosophila have become laboratory models for microbiota research, yet the bacteria commonly used in these experiments are rarely found in wild-caught flies and instead represent bacteria also present in the food. 28939605 9 21 located found 2014:2018 arg2 bacteria 1959:1966 the bacteria 1955:1966 the bacteria commonly used in these experiments 1955:2001 Thus, these bacterial groups appear to be specialized to the insect gut environment, where they may colonize through direct host-to-host transmission in natural settings.IMPORTANCE Flies in the genus Drosophila have become laboratory models for microbiota research, yet the bacteria commonly used in these experiments are rarely found in wild-caught flies and instead represent bacteria also present in the food. 28939605 0 22 theme Cactophilic 69:79 arg1 Species 92:98 a Cactophilic Drosophila Species 67:98 a Cactophilic Drosophila Species 67:98 A Distinctive and Host-Restricted Gut Microbiota in Populations of a Cactophilic Drosophila Species. 28939605 10 23 theme bacterial 2215:2223 arg1 types 2225:2229 bacterial types 2215:2229 bacterial types absent from the flies' natural food but widespread in other wild-caught insects 2215:2309 This study shows that an ecologically specialized Drosophila species possesses a distinctive microbiome, composed of bacterial types absent from the flies' natural food but widespread in other wild-caught insects. 28939605 9 24 theme bacterial 1697:1705 arg1 groups 1707:1712 these bacterial groups 1691:1712 these bacterial groups 1691:1712 Thus, these bacterial groups appear to be specialized to the insect gut environment, where they may colonize through direct host-to-host transmission in natural settings.IMPORTANCE Flies in the genus Drosophila have become laboratory models for microbiota research, yet the bacteria commonly used in these experiments are rarely found in wild-caught flies and instead represent bacteria also present in the food. 28939605 6 25 from tissue 1141:1146 arg1 absent 1120:1125 absent 1120:1125 absent 1120:1125 The most abundant bacteria in the flies are rare or completely absent in the cactus tissue and are consistently abundant in flies from different cacti and localities. 28939605 0 26 theme Species 92:98 arg1 Populations 52:62 Populations 52:62 Populations of a Cactophilic Drosophila Species 52:98 A Distinctive and Host-Restricted Gut Microbiota in Populations of a Cactophilic Drosophila Species. 28939605 7 27 theme Drosophila 1485:1494 arg1 species 1496:1502 several Drosophila species 1477:1502 several Drosophila species 1477:1502 Several of these fly-associated bacterial groups, such as the bacterial order Orbales and the genera Serpens and Dysgonomonas, have been identified in prior surveys of insects from the orders Hymenoptera, Coleoptera, Lepidoptera, and Diptera, including several Drosophila species. 28939605 9 28 theme insect 1746:1751 arg1 environment 1757:1767 the insect gut environment 1742:1767 the insect gut environment 1742:1767 Thus, these bacterial groups appear to be specialized to the insect gut environment, where they may colonize through direct host-to-host transmission in natural settings.IMPORTANCE Flies in the genus Drosophila have become laboratory models for microbiota research, yet the bacteria commonly used in these experiments are rarely found in wild-caught flies and instead represent bacteria also present in the food. 28939605 2 29 theme melanogaster 426:437 arg1 studies 386:392 laboratory studies 375:392 laboratory studies 375:392 For example, in social bees and mammals, the composition is relatively constant within species and is dominated by specialist bacteria that do not live elsewhere; in laboratory studies and field surveys of Drosophila melanogaster, however, gut communities consist of bacteria that are ingested with food and that vary widely among individuals and localities. 28939605 2 29 theme melanogaster 426:437 arg1 surveys 404:410 field surveys 398:410 field surveys 398:410 For example, in social bees and mammals, the composition is relatively constant within species and is dominated by specialist bacteria that do not live elsewhere; in laboratory studies and field surveys of Drosophila melanogaster, however, gut communities consist of bacteria that are ingested with food and that vary widely among individuals and localities. 28939605 11 30 theme microbiota 2371:2380 arg1 research 2382:2389 fieldwork-informed microbiota research 2352:2389 fieldwork-informed microbiota research 2352:2389 This study highlights the importance of fieldwork-informed microbiota research. 28939605 6 31 from absent 1120:1125 arg1 tissue 1141:1146 the cactus tissue 1130:1146 the cactus tissue 1130:1146 The most abundant bacteria in the flies are rare or completely absent in the cactus tissue and are consistently abundant in flies from different cacti and localities. 28939605 2 32 theme field 398:402 arg1 surveys 404:410 field surveys 398:410 field surveys 398:410 For example, in social bees and mammals, the composition is relatively constant within species and is dominated by specialist bacteria that do not live elsewhere; in laboratory studies and field surveys of Drosophila melanogaster, however, gut communities consist of bacteria that are ingested with food and that vary widely among individuals and localities. 28939605 10 33 theme specialized 2136:2146 arg1 species 2159:2165 an ecologically specialized Drosophila species 2120:2165 an ecologically specialized Drosophila species 2120:2165 This study shows that an ecologically specialized Drosophila species possesses a distinctive microbiome, composed of bacterial types absent from the flies' natural food but widespread in other wild-caught insects. 28939605 1 34 theme all 108:110 arg1 animals 112:118 Almost all animals 101:118 Almost all animals 101:118 Almost all animals possess gut microbial communities, but the nature of these communities varies immensely. 28939605 7 35 theme bacterial 1256:1264 arg1 groups 1266:1271 these fly-associated bacterial groups 1235:1271 these fly-associated bacterial groups 1235:1271 Several of these fly-associated bacterial groups, such as the bacterial order Orbales and the genera Serpens and Dysgonomonas, have been identified in prior surveys of insects from the orders Hymenoptera, Coleoptera, Lepidoptera, and Diptera, including several Drosophila species. 28939605 2 36 theme gut 449:451 arg1 communities 453:463 gut communities 449:463 gut communities 449:463 For example, in social bees and mammals, the composition is relatively constant within species and is dominated by specialist bacteria that do not live elsewhere; in laboratory studies and field surveys of Drosophila melanogaster, however, gut communities consist of bacteria that are ingested with food and that vary widely among individuals and localities. 28939605 6 37 from abundant 1169:1176 arg1 flies 1181:1185 flies 1181:1185 flies from different cacti and localities 1181:1221 The most abundant bacteria in the flies are rare or completely absent in the cactus tissue and are consistently abundant in flies from different cacti and localities. 28939605 0 38 theme Gut 34:36 arg1 Microbiota 38:47 A Distinctive and Host-Restricted Gut Microbiota 0:47 A Distinctive and Host-Restricted Gut Microbiota in Populations of a Cactophilic Drosophila Species 0:98 A Distinctive and Host-Restricted Gut Microbiota in Populations of a Cactophilic Drosophila Species. 28939605 9 39 from present 2077:2083 arg1 food 2092:2095 the food 2088:2095 the food 2088:2095 Thus, these bacterial groups appear to be specialized to the insect gut environment, where they may colonize through direct host-to-host transmission in natural settings.IMPORTANCE Flies in the genus Drosophila have become laboratory models for microbiota research, yet the bacteria commonly used in these experiments are rarely found in wild-caught flies and instead represent bacteria also present in the food. 28939605 2 40 theme specialist 324:333 arg1 bacteria 335:342 specialist bacteria 324:342 specialist bacteria that do not live elsewhere 324:369 For example, in social bees and mammals, the composition is relatively constant within species and is dominated by specialist bacteria that do not live elsewhere; in laboratory studies and field surveys of Drosophila melanogaster, however, gut communities consist of bacteria that are ingested with food and that vary widely among individuals and localities. 28939605 6 41 from bacteria 1075:1082 arg1 flies 1091:1095 the flies 1087:1095 the flies 1087:1095 The most abundant bacteria in the flies are rare or completely absent in the cactus tissue and are consistently abundant in flies from different cacti and localities. 28939605 6 42 from localities 1212:1221 arg1 flies 1181:1185 flies 1181:1185 flies from different cacti and localities 1181:1221 The most abundant bacteria in the flies are rare or completely absent in the cactus tissue and are consistently abundant in flies from different cacti and localities. 28939605 9 43 theme settings.IMPORTANCE 1846:1864 arg1 Flies 1866:1870 natural settings.IMPORTANCE Flies 1838:1870 natural settings.IMPORTANCE Flies in the genus Drosophila 1838:1894 Thus, these bacterial groups appear to be specialized to the insect gut environment, where they may colonize through direct host-to-host transmission in natural settings.IMPORTANCE Flies in the genus Drosophila have become laboratory models for microbiota research, yet the bacteria commonly used in these experiments are rarely found in wild-caught flies and instead represent bacteria also present in the food. 28939605 8 44 theme groups 1547:1552 arg1 functions 1518:1526 the functions 1514:1526 the functions of these bacterial groups 1514:1552 Although the functions of these bacterial groups are mostly unexplored, Orbales species studied in bees are known to break down plant polysaccharides and use the resulting sugars. 28939605 4 45 dep pringlei 869:876 arg1 cactus 886:891 cardón cactus 879:891 cardón cactus 879:891 Drosophila nigrospiracula is a species that is endemic to the Sonoran Desert and is restricted to decaying tissues of two giant columnar cacti, Pachycereus pringlei (cardón cactus) and Carnegiea gigantea (saguaro cactus). 28939605 4 46 theme giant 835:839 arg1 gigantea 908:915 Carnegiea gigantea 898:915 Carnegiea gigantea (saguaro cactus) 898:932 Drosophila nigrospiracula is a species that is endemic to the Sonoran Desert and is restricted to decaying tissues of two giant columnar cacti, Pachycereus pringlei (cardón cactus) and Carnegiea gigantea (saguaro cactus). 28939605 4 46 theme giant 835:839 arg1 cacti 850:854 two giant columnar cacti 831:854 two giant columnar cacti 831:854 Drosophila nigrospiracula is a species that is endemic to the Sonoran Desert and is restricted to decaying tissues of two giant columnar cacti, Pachycereus pringlei (cardón cactus) and Carnegiea gigantea (saguaro cactus). 28939605 4 46 theme giant 835:839 arg1 pringlei 869:876 Pachycereus pringlei 857:876 Pachycereus pringlei (cardón cactus) 857:892 Drosophila nigrospiracula is a species that is endemic to the Sonoran Desert and is restricted to decaying tissues of two giant columnar cacti, Pachycereus pringlei (cardón cactus) and Carnegiea gigantea (saguaro cactus). 28939605 9 47 theme host-to-host 1809:1820 arg1 transmission 1822:1833 direct host-to-host transmission 1802:1833 direct host-to-host transmission 1802:1833 Thus, these bacterial groups appear to be specialized to the insect gut environment, where they may colonize through direct host-to-host transmission in natural settings.IMPORTANCE Flies in the genus Drosophila have become laboratory models for microbiota research, yet the bacteria commonly used in these experiments are rarely found in wild-caught flies and instead represent bacteria also present in the food. 28939605 3 48 theme gut 667:669 arg1 specialists 671:681 gut specialists 667:681 gut specialists 667:681 We addressed whether an ecological specialist in its natural habitat has a microbiota dominated by gut specialists or by environmental bacteria. 28939605 6 49 from cacti 1202:1206 arg1 flies 1181:1185 flies 1181:1185 flies from different cacti and localities 1181:1221 The most abundant bacteria in the flies are rare or completely absent in the cactus tissue and are consistently abundant in flies from different cacti and localities. 28939605 7 50 theme insects 1392:1398 arg1 surveys 1381:1387 prior surveys 1375:1387 prior surveys of insects from the orders Hymenoptera, Coleoptera, Lepidoptera, and Diptera, including several Drosophila species 1375:1502 Several of these fly-associated bacterial groups, such as the bacterial order Orbales and the genera Serpens and Dysgonomonas, have been identified in prior surveys of insects from the orders Hymenoptera, Coleoptera, Lepidoptera, and Diptera, including several Drosophila species. 28939605 4 51 theme cacti 850:854 arg1 tissues 820:826 decaying tissues 811:826 decaying tissues of two giant columnar cacti, Pachycereus pringlei (cardón cactus) and Carnegiea gigantea (saguaro cactus) 811:932 Drosophila nigrospiracula is a species that is endemic to the Sonoran Desert and is restricted to decaying tissues of two giant columnar cacti, Pachycereus pringlei (cardón cactus) and Carnegiea gigantea (saguaro cactus). 28939605 7 52 theme prior 1375:1379 arg1 surveys 1381:1387 prior surveys 1375:1387 prior surveys of insects from the orders Hymenoptera, Coleoptera, Lepidoptera, and Diptera, including several Drosophila species 1375:1502 Several of these fly-associated bacterial groups, such as the bacterial order Orbales and the genera Serpens and Dysgonomonas, have been identified in prior surveys of insects from the orders Hymenoptera, Coleoptera, Lepidoptera, and Diptera, including several Drosophila species. 28939605 10 53 from insects 2303:2309 arg1 widespread 2271:2280 widespread 2271:2280 widespread 2271:2280 This study shows that an ecologically specialized Drosophila species possesses a distinctive microbiome, composed of bacterial types absent from the flies' natural food but widespread in other wild-caught insects. 28939605 8 54 theme down 1628:1631 arg1 polysaccharides 1639:1653 down plant polysaccharides 1628:1653 down plant polysaccharides 1628:1653 Although the functions of these bacterial groups are mostly unexplored, Orbales species studied in bees are known to break down plant polysaccharides and use the resulting sugars. 28939605 4 55 theme decaying 811:818 arg1 tissues 820:826 decaying tissues 811:826 decaying tissues of two giant columnar cacti, Pachycereus pringlei (cardón cactus) and Carnegiea gigantea (saguaro cactus) 811:932 Drosophila nigrospiracula is a species that is endemic to the Sonoran Desert and is restricted to decaying tissues of two giant columnar cacti, Pachycereus pringlei (cardón cactus) and Carnegiea gigantea (saguaro cactus). 28939605 9 56 attach present 2077:2083 arg1 food 2092:2095 the food 2088:2095 the food 2088:2095 Thus, these bacterial groups appear to be specialized to the insect gut environment, where they may colonize through direct host-to-host transmission in natural settings.IMPORTANCE Flies in the genus Drosophila have become laboratory models for microbiota research, yet the bacteria commonly used in these experiments are rarely found in wild-caught flies and instead represent bacteria also present in the food. 28939605 9 56 attach present 2077:2083 arg2 bacteria 2063:2070 bacteria 2063:2070 bacteria also present in the food 2063:2095 Thus, these bacterial groups appear to be specialized to the insect gut environment, where they may colonize through direct host-to-host transmission in natural settings.IMPORTANCE Flies in the genus Drosophila have become laboratory models for microbiota research, yet the bacteria commonly used in these experiments are rarely found in wild-caught flies and instead represent bacteria also present in the food. 28939605 3 57 contain has 637:639 arg2 microbiota 643:652 a microbiota 641:652 a microbiota dominated by gut specialists or by environmental bacteria 641:710 We addressed whether an ecological specialist in its natural habitat has a microbiota dominated by gut specialists or by environmental bacteria. 28939605 3 57 contain has 637:639 arg1 specialist 603:612 an ecological specialist 589:612 an ecological specialist in its natural habitat 589:635 We addressed whether an ecological specialist in its natural habitat has a microbiota dominated by gut specialists or by environmental bacteria. 28939605 3 58 theme environmental 689:701 arg1 bacteria 703:710 environmental bacteria 689:710 environmental bacteria 689:710 We addressed whether an ecological specialist in its natural habitat has a microbiota dominated by gut specialists or by environmental bacteria. 28939605 10 59 theme widespread 2271:2280 arg1 types 2225:2229 bacterial types 2215:2229 bacterial types absent from the flies' natural food but widespread in other wild-caught insects 2215:2309 This study shows that an ecologically specialized Drosophila species possesses a distinctive microbiome, composed of bacterial types absent from the flies' natural food but widespread in other wild-caught insects. 28939605 2 60 theme social 225:230 arg1 bees 232:235 social bees 225:235 social bees 225:235 For example, in social bees and mammals, the composition is relatively constant within species and is dominated by specialist bacteria that do not live elsewhere; in laboratory studies and field surveys of Drosophila melanogaster, however, gut communities consist of bacteria that are ingested with food and that vary widely among individuals and localities. 28939605 8 61 theme resulting 1667:1675 arg1 sugars 1677:1682 the resulting sugars 1663:1682 the resulting sugars 1663:1682 Although the functions of these bacterial groups are mostly unexplored, Orbales species studied in bees are known to break down plant polysaccharides and use the resulting sugars. 28939605 7 62 from orders 1409:1414 arg1 insects 1392:1398 insects 1392:1398 insects 1392:1398 Several of these fly-associated bacterial groups, such as the bacterial order Orbales and the genera Serpens and Dysgonomonas, have been identified in prior surveys of insects from the orders Hymenoptera, Coleoptera, Lepidoptera, and Diptera, including several Drosophila species. 28939605 7 62 from orders 1409:1414 arg1 species 1496:1502 several Drosophila species 1477:1502 several Drosophila species 1477:1502 Several of these fly-associated bacterial groups, such as the bacterial order Orbales and the genera Serpens and Dysgonomonas, have been identified in prior surveys of insects from the orders Hymenoptera, Coleoptera, Lepidoptera, and Diptera, including several Drosophila species. 28939605 7 62 from orders 1409:1414 arg1 surveys 1381:1387 prior surveys 1375:1387 prior surveys of insects from the orders Hymenoptera, Coleoptera, Lepidoptera, and Diptera, including several Drosophila species 1375:1502 Several of these fly-associated bacterial groups, such as the bacterial order Orbales and the genera Serpens and Dysgonomonas, have been identified in prior surveys of insects from the orders Hymenoptera, Coleoptera, Lepidoptera, and Diptera, including several Drosophila species. 28939605 9 63 theme laboratory 1908:1917 arg1 models 1919:1924 laboratory models 1908:1924 laboratory models for microbiota research 1908:1948 Thus, these bacterial groups appear to be specialized to the insect gut environment, where they may colonize through direct host-to-host transmission in natural settings.IMPORTANCE Flies in the genus Drosophila have become laboratory models for microbiota research, yet the bacteria commonly used in these experiments are rarely found in wild-caught flies and instead represent bacteria also present in the food. 28939605 3 64 theme ecological 592:601 arg1 specialist 603:612 an ecological specialist 589:612 an ecological specialist in its natural habitat 589:635 We addressed whether an ecological specialist in its natural habitat has a microbiota dominated by gut specialists or by environmental bacteria. 28939605 1 65 theme gut 128:130 arg1 communities 142:152 gut microbial communities 128:152 gut microbial communities 128:152 Almost all animals possess gut microbial communities, but the nature of these communities varies immensely. 28939605 10 66 theme other 2285:2289 arg1 insects 2303:2309 other wild-caught insects 2285:2309 other wild-caught insects 2285:2309 This study shows that an ecologically specialized Drosophila species possesses a distinctive microbiome, composed of bacterial types absent from the flies' natural food but widespread in other wild-caught insects. 28939605 9 67 from Flies 1866:1870 arg1 Drosophila 1885:1894 genus Drosophila 1879:1894 the genus Drosophila 1875:1894 Thus, these bacterial groups appear to be specialized to the insect gut environment, where they may colonize through direct host-to-host transmission in natural settings.IMPORTANCE Flies in the genus Drosophila have become laboratory models for microbiota research, yet the bacteria commonly used in these experiments are rarely found in wild-caught flies and instead represent bacteria also present in the food. 28939605 10 68 theme Drosophila 2148:2157 arg1 species 2159:2165 an ecologically specialized Drosophila species 2120:2165 an ecologically specialized Drosophila species 2120:2165 This study shows that an ecologically specialized Drosophila species possesses a distinctive microbiome, composed of bacterial types absent from the flies' natural food but widespread in other wild-caught insects. 28939605 10 69 contain possesses 2167:2175 arg1 species 2159:2165 an ecologically specialized Drosophila species 2120:2165 an ecologically specialized Drosophila species 2120:2165 This study shows that an ecologically specialized Drosophila species possesses a distinctive microbiome, composed of bacterial types absent from the flies' natural food but widespread in other wild-caught insects. 28939605 10 69 contain possesses 2167:2175 arg2 microbiome 2191:2200 a distinctive microbiome 2177:2200 a distinctive microbiome 2177:2200 This study shows that an ecologically specialized Drosophila species possesses a distinctive microbiome, composed of bacterial types absent from the flies' natural food but widespread in other wild-caught insects. 28939605 5 70 theme cactus 1018:1023 arg1 tissue 1025:1030 the cactus tissue 1014:1030 the cactus tissue on which the flies feed 1014:1054 We found that the D. nigrospiracula microbiota differs strikingly from that of the cactus tissue on which the flies feed. 28939605 0 71 theme Drosophila 81:90 arg1 Species 92:98 a Cactophilic Drosophila Species 67:98 a Cactophilic Drosophila Species 67:98 A Distinctive and Host-Restricted Gut Microbiota in Populations of a Cactophilic Drosophila Species. 28939605 2 72 from constant 280:287 arg1 mammals 241:247 mammals 241:247 mammals 241:247 For example, in social bees and mammals, the composition is relatively constant within species and is dominated by specialist bacteria that do not live elsewhere; in laboratory studies and field surveys of Drosophila melanogaster, however, gut communities consist of bacteria that are ingested with food and that vary widely among individuals and localities. 28939605 2 72 from constant 280:287 arg1 bees 232:235 social bees 225:235 social bees 225:235 For example, in social bees and mammals, the composition is relatively constant within species and is dominated by specialist bacteria that do not live elsewhere; in laboratory studies and field surveys of Drosophila melanogaster, however, gut communities consist of bacteria that are ingested with food and that vary widely among individuals and localities. 28939605 10 73 theme distinctive 2179:2189 arg1 microbiome 2191:2200 a distinctive microbiome 2177:2200 a distinctive microbiome 2177:2200 This study shows that an ecologically specialized Drosophila species possesses a distinctive microbiome, composed of bacterial types absent from the flies' natural food but widespread in other wild-caught insects. 28939605 10 74 from widespread 2271:2280 arg1 insects 2303:2309 other wild-caught insects 2285:2309 other wild-caught insects 2285:2309 This study shows that an ecologically specialized Drosophila species possesses a distinctive microbiome, composed of bacterial types absent from the flies' natural food but widespread in other wild-caught insects. 28939605 7 75 theme several 1477:1483 arg1 species 1496:1502 several Drosophila species 1477:1502 several Drosophila species 1477:1502 Several of these fly-associated bacterial groups, such as the bacterial order Orbales and the genera Serpens and Dysgonomonas, have been identified in prior surveys of insects from the orders Hymenoptera, Coleoptera, Lepidoptera, and Diptera, including several Drosophila species. 28939605 0 76 from Microbiota 38:47 arg1 Populations 52:62 Populations 52:62 Populations of a Cactophilic Drosophila Species 52:98 A Distinctive and Host-Restricted Gut Microbiota in Populations of a Cactophilic Drosophila Species. 28939605 11 77 theme fieldwork-informed 2352:2369 arg1 research 2382:2389 fieldwork-informed microbiota research 2352:2389 fieldwork-informed microbiota research 2352:2389 This study highlights the importance of fieldwork-informed microbiota research. 28939605 10 78 from food 2262:2265 arg1 absent 2231:2236 absent 2231:2236 absent 2231:2236 This study shows that an ecologically specialized Drosophila species possesses a distinctive microbiome, composed of bacterial types absent from the flies' natural food but widespread in other wild-caught insects. 28939605 9 79 from food 2092:2095 arg1 present 2077:2083 present 2077:2083 present 2077:2083 Thus, these bacterial groups appear to be specialized to the insect gut environment, where they may colonize through direct host-to-host transmission in natural settings.IMPORTANCE Flies in the genus Drosophila have become laboratory models for microbiota research, yet the bacteria commonly used in these experiments are rarely found in wild-caught flies and instead represent bacteria also present in the food. 28939605 7 80 theme groups 1266:1271 arg1 Several 1224:1230 Several 1224:1230 Several 1224:1230 Several of these fly-associated bacterial groups, such as the bacterial order Orbales and the genera Serpens and Dysgonomonas, have been identified in prior surveys of insects from the orders Hymenoptera, Coleoptera, Lepidoptera, and Diptera, including several Drosophila species. 28939605 4 81 theme Drosophila 713:722 arg1 restricted 797:806 restricted 797:806 restricted 797:806 Drosophila nigrospiracula is a species that is endemic to the Sonoran Desert and is restricted to decaying tissues of two giant columnar cacti, Pachycereus pringlei (cardón cactus) and Carnegiea gigantea (saguaro cactus). 28939605 4 81 theme Drosophila 713:722 arg1 nigrospiracula 724:737 Drosophila nigrospiracula 713:737 Drosophila nigrospiracula 713:737 Drosophila nigrospiracula is a species that is endemic to the Sonoran Desert and is restricted to decaying tissues of two giant columnar cacti, Pachycereus pringlei (cardón cactus) and Carnegiea gigantea (saguaro cactus). 28939605 4 81 theme Drosophila 713:722 arg1 species 744:750 a species 742:750 a species that is endemic to the Sonoran Desert and is restricted to decaying tissues of two giant columnar cacti, Pachycereus pringlei (cardón cactus) and Carnegiea gigantea (saguaro cactus) 742:932 Drosophila nigrospiracula is a species that is endemic to the Sonoran Desert and is restricted to decaying tissues of two giant columnar cacti, Pachycereus pringlei (cardón cactus) and Carnegiea gigantea (saguaro cactus). 28939605 4 81 theme Drosophila 713:722 arg1 endemic 760:766 endemic 760:766 endemic 760:766 Drosophila nigrospiracula is a species that is endemic to the Sonoran Desert and is restricted to decaying tissues of two giant columnar cacti, Pachycereus pringlei (cardón cactus) and Carnegiea gigantea (saguaro cactus). 28939605 0 82 theme Host-Restricted 18:32 arg1 Microbiota 38:47 A Distinctive and Host-Restricted Gut Microbiota 0:47 A Distinctive and Host-Restricted Gut Microbiota in Populations of a Cactophilic Drosophila Species 0:98 A Distinctive and Host-Restricted Gut Microbiota in Populations of a Cactophilic Drosophila Species. 28939605 7 83 dep orders 1409:1414 arg1 Lepidoptera 1441:1451 Lepidoptera 1441:1451 Lepidoptera 1441:1451 Several of these fly-associated bacterial groups, such as the bacterial order Orbales and the genera Serpens and Dysgonomonas, have been identified in prior surveys of insects from the orders Hymenoptera, Coleoptera, Lepidoptera, and Diptera, including several Drosophila species. 28939605 7 83 dep orders 1409:1414 arg1 Diptera 1458:1464 Diptera 1458:1464 Diptera 1458:1464 Several of these fly-associated bacterial groups, such as the bacterial order Orbales and the genera Serpens and Dysgonomonas, have been identified in prior surveys of insects from the orders Hymenoptera, Coleoptera, Lepidoptera, and Diptera, including several Drosophila species. 28939605 7 83 dep orders 1409:1414 arg1 Coleoptera 1429:1438 Coleoptera 1429:1438 Coleoptera 1429:1438 Several of these fly-associated bacterial groups, such as the bacterial order Orbales and the genera Serpens and Dysgonomonas, have been identified in prior surveys of insects from the orders Hymenoptera, Coleoptera, Lepidoptera, and Diptera, including several Drosophila species. 28939605 7 83 dep orders 1409:1414 arg1 orders 1409:1414 the orders 1405:1414 the orders Hymenoptera, Coleoptera, Lepidoptera, and Diptera 1405:1464 Several of these fly-associated bacterial groups, such as the bacterial order Orbales and the genera Serpens and Dysgonomonas, have been identified in prior surveys of insects from the orders Hymenoptera, Coleoptera, Lepidoptera, and Diptera, including several Drosophila species. 28939605 2 84 from bees 232:235 arg1 composition 254:264 the composition 250:264 the composition 250:264 For example, in social bees and mammals, the composition is relatively constant within species and is dominated by specialist bacteria that do not live elsewhere; in laboratory studies and field surveys of Drosophila melanogaster, however, gut communities consist of bacteria that are ingested with food and that vary widely among individuals and localities. 28939605 2 84 from bees 232:235 arg1 constant 280:287 constant 280:287 constant 280:287 For example, in social bees and mammals, the composition is relatively constant within species and is dominated by specialist bacteria that do not live elsewhere; in laboratory studies and field surveys of Drosophila melanogaster, however, gut communities consist of bacteria that are ingested with food and that vary widely among individuals and localities. 28939605 7 85 theme fly-associated 1241:1254 arg1 groups 1266:1271 these fly-associated bacterial groups 1235:1271 these fly-associated bacterial groups 1235:1271 Several of these fly-associated bacterial groups, such as the bacterial order Orbales and the genera Serpens and Dysgonomonas, have been identified in prior surveys of insects from the orders Hymenoptera, Coleoptera, Lepidoptera, and Diptera, including several Drosophila species. 28939605 3 86 theme natural 621:627 arg1 habitat 629:635 its natural habitat 617:635 its natural habitat 617:635 We addressed whether an ecological specialist in its natural habitat has a microbiota dominated by gut specialists or by environmental bacteria. 28939605 2 87 from mammals 241:247 arg1 composition 254:264 the composition 250:264 the composition 250:264 For example, in social bees and mammals, the composition is relatively constant within species and is dominated by specialist bacteria that do not live elsewhere; in laboratory studies and field surveys of Drosophila melanogaster, however, gut communities consist of bacteria that are ingested with food and that vary widely among individuals and localities. 28939605 2 87 from mammals 241:247 arg1 constant 280:287 constant 280:287 constant 280:287 For example, in social bees and mammals, the composition is relatively constant within species and is dominated by specialist bacteria that do not live elsewhere; in laboratory studies and field surveys of Drosophila melanogaster, however, gut communities consist of bacteria that are ingested with food and that vary widely among individuals and localities. 28939605 9 88 theme gut 1753:1755 arg1 environment 1757:1767 the insect gut environment 1742:1767 the insect gut environment 1742:1767 Thus, these bacterial groups appear to be specialized to the insect gut environment, where they may colonize through direct host-to-host transmission in natural settings.IMPORTANCE Flies in the genus Drosophila have become laboratory models for microbiota research, yet the bacteria commonly used in these experiments are rarely found in wild-caught flies and instead represent bacteria also present in the food. 28939605 2 89 theme laboratory 375:384 arg1 studies 386:392 laboratory studies 375:392 laboratory studies 375:392 For example, in social bees and mammals, the composition is relatively constant within species and is dominated by specialist bacteria that do not live elsewhere; in laboratory studies and field surveys of Drosophila melanogaster, however, gut communities consist of bacteria that are ingested with food and that vary widely among individuals and localities. 28939605 9 90 theme wild-caught 2023:2033 arg1 flies 2035:2039 wild-caught flies 2023:2039 wild-caught flies 2023:2039 Thus, these bacterial groups appear to be specialized to the insect gut environment, where they may colonize through direct host-to-host transmission in natural settings.IMPORTANCE Flies in the genus Drosophila have become laboratory models for microbiota research, yet the bacteria commonly used in these experiments are rarely found in wild-caught flies and instead represent bacteria also present in the food. 28939605 6 91 theme abundant 1066:1073 arg1 abundant 1169:1176 abundant 1169:1176 abundant 1169:1176 The most abundant bacteria in the flies are rare or completely absent in the cactus tissue and are consistently abundant in flies from different cacti and localities. 28939605 6 91 theme abundant 1066:1073 arg1 rare 1101:1104 rare 1101:1104 rare 1101:1104 The most abundant bacteria in the flies are rare or completely absent in the cactus tissue and are consistently abundant in flies from different cacti and localities. 28939605 6 91 theme abundant 1066:1073 arg1 bacteria 1075:1082 The most abundant bacteria 1057:1082 The most abundant bacteria in the flies 1057:1095 The most abundant bacteria in the flies are rare or completely absent in the cactus tissue and are consistently abundant in flies from different cacti and localities. 28939605 8 92 theme bacterial 1537:1545 arg1 groups 1547:1552 these bacterial groups 1531:1552 these bacterial groups 1531:1552 Although the functions of these bacterial groups are mostly unexplored, Orbales species studied in bees are known to break down plant polysaccharides and use the resulting sugars. 28939605 5 93 theme D. 953:954 arg1 microbiota 971:980 the D. nigrospiracula microbiota 949:980 the D. nigrospiracula microbiota 949:980 We found that the D. nigrospiracula microbiota differs strikingly from that of the cactus tissue on which the flies feed. 28939605 4 94 theme Sonoran 775:781 arg1 Desert 783:788 the Sonoran Desert 771:788 the Sonoran Desert 771:788 Drosophila nigrospiracula is a species that is endemic to the Sonoran Desert and is restricted to decaying tissues of two giant columnar cacti, Pachycereus pringlei (cardón cactus) and Carnegiea gigantea (saguaro cactus). 28939605 0 95 theme Distinctive 2:12 arg1 Microbiota 38:47 A Distinctive and Host-Restricted Gut Microbiota 0:47 A Distinctive and Host-Restricted Gut Microbiota in Populations of a Cactophilic Drosophila Species 0:98 A Distinctive and Host-Restricted Gut Microbiota in Populations of a Cactophilic Drosophila Species. 28607074 6 0 theme molecular 1150:1158 arg1 markers 1160:1166 molecular markers 1150:1166 molecular markers reflecting a diversity of specific xylan, xyloglucan, pectin, and arabinogalactan moieties 1150:1257 We undertook genome-wide association analysis of data collected from 57 carbohydrate microarrays and identified molecular markers reflecting a diversity of specific xylan, xyloglucan, pectin, and arabinogalactan moieties. 28607074 4 1 theme phenotyping 541:551 arg1 methodologies 553:565 few cell wall phenotyping methodologies 527:565 few cell wall phenotyping methodologies 527:565 However, few cell wall phenotyping methodologies have proven sufficiently precise, robust, or scalable for association mapping to be conducted for specific cell wall polymers. 28607074 3 2 theme incomplete 473:482 arg1 knowledge 484:492 our currently incomplete knowledge 459:492 our currently incomplete knowledge of cell wall synthesis 459:515 Association mapping is one of the few techniques that can help identify candidate genes without relying on our currently incomplete knowledge of cell wall synthesis. 28607074 1 3 theme fuels 227:231 arg1 quality 198:204 the quality 194:204 the quality of food, fibers, and fuels 194:231 Genetic improvement of the plant cell wall has enormous potential to increase the quality of food, fibers, and fuels. 28607074 6 4 theme arabinogalactan 1234:1248 arg1 moieties 1250:1257 specific xylan, xyloglucan, pectin, and arabinogalactan moieties 1194:1257 specific xylan, xyloglucan, pectin, and arabinogalactan moieties 1194:1257 We undertook genome-wide association analysis of data collected from 57 carbohydrate microarrays and identified molecular markers reflecting a diversity of specific xylan, xyloglucan, pectin, and arabinogalactan moieties. 28607074 8 5 theme plant 1727:1731 arg1 biosynthesis 1743:1754 plant cell wall biosynthesis 1727:1754 plant cell wall biosynthesis 1727:1754 The identified markers also have value beyond B. napus for functional genomics, facilitated by the close genetic relatedness to the model plant Arabidopsis Together, our findings provide a unique dissection of the genetic architecture that underpins plant cell wall biosynthesis and restructuring. 28607074 7 6 from variations 1319:1328 arg1 moieties 1356:1363 cell wall carbohydrate moieties 1333:1363 cell wall carbohydrate moieties 1333:1363 These datasets provide a detailed insight into the natural variations in cell wall carbohydrate moieties between B. napus genotypes and identify associated markers that could be exploited by marker-assisted breeding. 28607074 4 7 theme association 625:635 arg1 mapping 637:643 association mapping 625:643 association mapping to be conducted for specific cell wall polymers 625:691 However, few cell wall phenotyping methodologies have proven sufficiently precise, robust, or scalable for association mapping to be conducted for specific cell wall polymers. 28607074 3 8 theme wall 502:505 arg1 synthesis 507:515 cell wall synthesis 497:515 cell wall synthesis 497:515 Association mapping is one of the few techniques that can help identify candidate genes without relying on our currently incomplete knowledge of cell wall synthesis. 28607074 1 9 theme enormous 163:170 arg1 potential 172:180 enormous potential 163:180 enormous potential 163:180 Genetic improvement of the plant cell wall has enormous potential to increase the quality of food, fibers, and fuels. 28607074 0 10 theme molecular 65:73 arg1 markers 75:81 molecular markers 65:81 molecular markers for plant cell wall composition 65:113 Carbohydrate microarrays and their use for the identification of molecular markers for plant cell wall composition. 28607074 2 11 theme genes 286:290 arg1 identification 247:260 identification 247:260 identification 247:260 However, the identification and characterization of genes involved in plant cell wall synthesis is far from complete. 28607074 2 11 theme genes 286:290 arg1 characterization 266:281 characterization 266:281 characterization 266:281 However, the identification and characterization of genes involved in plant cell wall synthesis is far from complete. 28607074 5 12 theme diverse 838:844 arg1 cultivars 861:869 331 genetically diverse Brassica napus cultivars 822:869 331 genetically diverse Brassica napus cultivars 822:869 Here, we created high-density carbohydrate microarrays containing chemically extracted cell wall polysaccharides collected from 331 genetically diverse Brassica napus cultivars and used them to obtain detailed, quantitative information describing the relative abundance of selected noncellulosic polysaccharide linkages and primary structures. 28607074 7 13 theme marker-assisted 1451:1465 arg1 breeding 1467:1474 marker-assisted breeding 1451:1474 marker-assisted breeding 1451:1474 These datasets provide a detailed insight into the natural variations in cell wall carbohydrate moieties between B. napus genotypes and identify associated markers that could be exploited by marker-assisted breeding. 28607074 8 14 theme architecture 1699:1710 arg1 dissection 1673:1682 a unique dissection 1664:1682 a unique dissection of the genetic architecture that underpins plant cell wall biosynthesis and restructuring 1664:1772 The identified markers also have value beyond B. napus for functional genomics, facilitated by the close genetic relatedness to the model plant Arabidopsis Together, our findings provide a unique dissection of the genetic architecture that underpins plant cell wall biosynthesis and restructuring. 28607074 5 15 theme napus 855:859 arg1 cultivars 861:869 331 genetically diverse Brassica napus cultivars 822:869 331 genetically diverse Brassica napus cultivars 822:869 Here, we created high-density carbohydrate microarrays containing chemically extracted cell wall polysaccharides collected from 331 genetically diverse Brassica napus cultivars and used them to obtain detailed, quantitative information describing the relative abundance of selected noncellulosic polysaccharide linkages and primary structures. 28607074 4 16 theme wall 679:682 arg1 polymers 684:691 specific cell wall polymers 665:691 specific cell wall polymers 665:691 However, few cell wall phenotyping methodologies have proven sufficiently precise, robust, or scalable for association mapping to be conducted for specific cell wall polymers. 28607074 1 17 theme Genetic 116:122 arg1 improvement 124:134 Genetic improvement 116:134 Genetic improvement of the plant cell wall 116:157 Genetic improvement of the plant cell wall has enormous potential to increase the quality of food, fibers, and fuels. 28607074 6 18 theme association 1063:1073 arg1 analysis 1075:1082 genome-wide association analysis 1051:1082 genome-wide association analysis of data collected from 57 carbohydrate microarrays 1051:1133 We undertook genome-wide association analysis of data collected from 57 carbohydrate microarrays and identified molecular markers reflecting a diversity of specific xylan, xyloglucan, pectin, and arabinogalactan moieties. 28607074 5 19 theme carbohydrate 724:735 arg1 microarrays 737:747 high-density carbohydrate microarrays 711:747 high-density carbohydrate microarrays containing chemically extracted cell wall polysaccharides collected from 331 genetically diverse Brassica napus cultivars 711:869 Here, we created high-density carbohydrate microarrays containing chemically extracted cell wall polysaccharides collected from 331 genetically diverse Brassica napus cultivars and used them to obtain detailed, quantitative information describing the relative abundance of selected noncellulosic polysaccharide linkages and primary structures. 28607074 1 20 theme plant 143:147 arg1 wall 154:157 the plant cell wall 139:157 the plant cell wall 139:157 Genetic improvement of the plant cell wall has enormous potential to increase the quality of food, fibers, and fuels. 28607074 4 21 theme specific 665:672 arg1 polymers 684:691 specific cell wall polymers 665:691 specific cell wall polymers 665:691 However, few cell wall phenotyping methodologies have proven sufficiently precise, robust, or scalable for association mapping to be conducted for specific cell wall polymers. 28607074 0 22 theme markers 75:81 arg1 identification 47:60 the identification 43:60 the identification of molecular markers for plant cell wall composition 43:113 Carbohydrate microarrays and their use for the identification of molecular markers for plant cell wall composition. 28607074 1 23 theme wall 154:157 arg1 improvement 124:134 Genetic improvement 116:134 Genetic improvement of the plant cell wall 116:157 Genetic improvement of the plant cell wall has enormous potential to increase the quality of food, fibers, and fuels. 28607074 8 24 theme genetic 1582:1588 arg1 relatedness 1590:1600 the close genetic relatedness 1572:1600 the close genetic relatedness to the model plant Arabidopsis 1572:1631 The identified markers also have value beyond B. napus for functional genomics, facilitated by the close genetic relatedness to the model plant Arabidopsis Together, our findings provide a unique dissection of the genetic architecture that underpins plant cell wall biosynthesis and restructuring. 28607074 0 25 theme plant 87:91 arg1 composition 103:113 plant cell wall composition 87:113 plant cell wall composition 87:113 Carbohydrate microarrays and their use for the identification of molecular markers for plant cell wall composition. 28607074 5 26 theme polysaccharide 990:1003 arg1 linkages 1005:1012 selected noncellulosic polysaccharide linkages 967:1012 selected noncellulosic polysaccharide linkages 967:1012 Here, we created high-density carbohydrate microarrays containing chemically extracted cell wall polysaccharides collected from 331 genetically diverse Brassica napus cultivars and used them to obtain detailed, quantitative information describing the relative abundance of selected noncellulosic polysaccharide linkages and primary structures. 28607074 0 27 theme wall 98:101 arg1 composition 103:113 plant cell wall composition 87:113 plant cell wall composition 87:113 Carbohydrate microarrays and their use for the identification of molecular markers for plant cell wall composition. 28607074 7 28 theme associated 1405:1414 arg1 markers 1416:1422 associated markers 1405:1422 associated markers that could be exploited by marker-assisted breeding 1405:1474 These datasets provide a detailed insight into the natural variations in cell wall carbohydrate moieties between B. napus genotypes and identify associated markers that could be exploited by marker-assisted breeding. 28607074 3 29 theme Association 352:362 arg1 mapping 364:370 Association mapping 352:370 Association mapping 352:370 Association mapping is one of the few techniques that can help identify candidate genes without relying on our currently incomplete knowledge of cell wall synthesis. 28607074 8 30 theme model 1609:1613 arg1 Arabidopsis 1621:1631 the model plant Arabidopsis 1605:1631 the model plant Arabidopsis 1605:1631 The identified markers also have value beyond B. napus for functional genomics, facilitated by the close genetic relatedness to the model plant Arabidopsis Together, our findings provide a unique dissection of the genetic architecture that underpins plant cell wall biosynthesis and restructuring. 28607074 7 31 theme detailed 1285:1292 arg1 insight 1294:1300 a detailed insight 1283:1300 a detailed insight into the natural variations in cell wall carbohydrate moieties between B. napus genotypes 1283:1390 These datasets provide a detailed insight into the natural variations in cell wall carbohydrate moieties between B. napus genotypes and identify associated markers that could be exploited by marker-assisted breeding. 28607074 5 32 dep detailed 895:902 arg1 quantitative 905:916 quantitative 905:916 quantitative 905:916 Here, we created high-density carbohydrate microarrays containing chemically extracted cell wall polysaccharides collected from 331 genetically diverse Brassica napus cultivars and used them to obtain detailed, quantitative information describing the relative abundance of selected noncellulosic polysaccharide linkages and primary structures. 28607074 3 33 theme few 386:388 arg1 techniques 390:399 the few techniques 382:399 the few techniques 382:399 Association mapping is one of the few techniques that can help identify candidate genes without relying on our currently incomplete knowledge of cell wall synthesis. 28607074 0 34 theme Carbohydrate 0:11 arg1 microarrays 13:23 Carbohydrate microarrays 0:23 Carbohydrate microarrays 0:23 Carbohydrate microarrays and their use for the identification of molecular markers for plant cell wall composition. 28607074 3 35 theme candidate 424:432 arg1 genes 434:438 candidate genes 424:438 candidate genes 424:438 Association mapping is one of the few techniques that can help identify candidate genes without relying on our currently incomplete knowledge of cell wall synthesis. 28607074 5 36 theme selected 967:974 arg1 linkages 1005:1012 selected noncellulosic polysaccharide linkages 967:1012 selected noncellulosic polysaccharide linkages 967:1012 Here, we created high-density carbohydrate microarrays containing chemically extracted cell wall polysaccharides collected from 331 genetically diverse Brassica napus cultivars and used them to obtain detailed, quantitative information describing the relative abundance of selected noncellulosic polysaccharide linkages and primary structures. 28607074 7 37 theme napus 1376:1380 arg1 genotypes 1382:1390 B. napus genotypes 1373:1390 B. napus genotypes 1373:1390 These datasets provide a detailed insight into the natural variations in cell wall carbohydrate moieties between B. napus genotypes and identify associated markers that could be exploited by marker-assisted breeding. 28607074 4 38 theme few 527:529 arg1 methodologies 553:565 few cell wall phenotyping methodologies 527:565 few cell wall phenotyping methodologies 527:565 However, few cell wall phenotyping methodologies have proven sufficiently precise, robust, or scalable for association mapping to be conducted for specific cell wall polymers. 28607074 5 39 theme extracted 771:779 arg1 polysaccharides 791:805 chemically extracted cell wall polysaccharides 760:805 chemically extracted cell wall polysaccharides collected from 331 genetically diverse Brassica napus cultivars 760:869 Here, we created high-density carbohydrate microarrays containing chemically extracted cell wall polysaccharides collected from 331 genetically diverse Brassica napus cultivars and used them to obtain detailed, quantitative information describing the relative abundance of selected noncellulosic polysaccharide linkages and primary structures. 28607074 1 40 contain has 159:161 arg1 improvement 124:134 Genetic improvement 116:134 Genetic improvement of the plant cell wall 116:157 Genetic improvement of the plant cell wall has enormous potential to increase the quality of food, fibers, and fuels. 28607074 1 40 contain has 159:161 arg2 potential 172:180 enormous potential 163:180 enormous potential 163:180 Genetic improvement of the plant cell wall has enormous potential to increase the quality of food, fibers, and fuels. 28607074 2 41 theme wall 315:318 arg1 synthesis 320:328 plant cell wall synthesis 304:328 plant cell wall synthesis 304:328 However, the identification and characterization of genes involved in plant cell wall synthesis is far from complete. 28607074 5 42 theme wall 786:789 arg1 polysaccharides 791:805 chemically extracted cell wall polysaccharides 760:805 chemically extracted cell wall polysaccharides collected from 331 genetically diverse Brassica napus cultivars 760:869 Here, we created high-density carbohydrate microarrays containing chemically extracted cell wall polysaccharides collected from 331 genetically diverse Brassica napus cultivars and used them to obtain detailed, quantitative information describing the relative abundance of selected noncellulosic polysaccharide linkages and primary structures. 28607074 5 43 contain containing 749:758 arg1 microarrays 737:747 high-density carbohydrate microarrays 711:747 high-density carbohydrate microarrays containing chemically extracted cell wall polysaccharides collected from 331 genetically diverse Brassica napus cultivars 711:869 Here, we created high-density carbohydrate microarrays containing chemically extracted cell wall polysaccharides collected from 331 genetically diverse Brassica napus cultivars and used them to obtain detailed, quantitative information describing the relative abundance of selected noncellulosic polysaccharide linkages and primary structures. 28607074 5 43 contain containing 749:758 arg2 polysaccharides 791:805 chemically extracted cell wall polysaccharides 760:805 chemically extracted cell wall polysaccharides collected from 331 genetically diverse Brassica napus cultivars 760:869 Here, we created high-density carbohydrate microarrays containing chemically extracted cell wall polysaccharides collected from 331 genetically diverse Brassica napus cultivars and used them to obtain detailed, quantitative information describing the relative abundance of selected noncellulosic polysaccharide linkages and primary structures. 28607074 7 44 theme carbohydrate 1343:1354 arg1 moieties 1356:1363 cell wall carbohydrate moieties 1333:1363 cell wall carbohydrate moieties 1333:1363 These datasets provide a detailed insight into the natural variations in cell wall carbohydrate moieties between B. napus genotypes and identify associated markers that could be exploited by marker-assisted breeding. 28607074 2 45 theme plant 304:308 arg1 synthesis 320:328 plant cell wall synthesis 304:328 plant cell wall synthesis 304:328 However, the identification and characterization of genes involved in plant cell wall synthesis is far from complete. 28607074 8 46 theme cell 1733:1736 arg1 biosynthesis 1743:1754 plant cell wall biosynthesis 1727:1754 plant cell wall biosynthesis 1727:1754 The identified markers also have value beyond B. napus for functional genomics, facilitated by the close genetic relatedness to the model plant Arabidopsis Together, our findings provide a unique dissection of the genetic architecture that underpins plant cell wall biosynthesis and restructuring. 28607074 1 47 theme food 209:212 arg1 quality 198:204 the quality 194:204 the quality of food, fibers, and fuels 194:231 Genetic improvement of the plant cell wall has enormous potential to increase the quality of food, fibers, and fuels. 28607074 5 48 theme structures 1026:1035 arg1 abundance 954:962 the relative abundance 941:962 the relative abundance of selected noncellulosic polysaccharide linkages and primary structures 941:1035 Here, we created high-density carbohydrate microarrays containing chemically extracted cell wall polysaccharides collected from 331 genetically diverse Brassica napus cultivars and used them to obtain detailed, quantitative information describing the relative abundance of selected noncellulosic polysaccharide linkages and primary structures. 28607074 7 49 theme cell 1333:1336 arg1 moieties 1356:1363 cell wall carbohydrate moieties 1333:1363 cell wall carbohydrate moieties 1333:1363 These datasets provide a detailed insight into the natural variations in cell wall carbohydrate moieties between B. napus genotypes and identify associated markers that could be exploited by marker-assisted breeding. 28607074 1 50 theme fibers 215:220 arg1 quality 198:204 the quality 194:204 the quality of food, fibers, and fuels 194:231 Genetic improvement of the plant cell wall has enormous potential to increase the quality of food, fibers, and fuels. 28607074 4 51 theme wall 536:539 arg1 methodologies 553:565 few cell wall phenotyping methodologies 527:565 few cell wall phenotyping methodologies 527:565 However, few cell wall phenotyping methodologies have proven sufficiently precise, robust, or scalable for association mapping to be conducted for specific cell wall polymers. 28607074 3 52 theme synthesis 507:515 arg1 knowledge 484:492 our currently incomplete knowledge 459:492 our currently incomplete knowledge of cell wall synthesis 459:515 Association mapping is one of the few techniques that can help identify candidate genes without relying on our currently incomplete knowledge of cell wall synthesis. 28607074 5 53 theme detailed 895:902 arg1 information 918:928 detailed, quantitative information 895:928 detailed, quantitative information describing the relative abundance of selected noncellulosic polysaccharide linkages and primary structures 895:1035 Here, we created high-density carbohydrate microarrays containing chemically extracted cell wall polysaccharides collected from 331 genetically diverse Brassica napus cultivars and used them to obtain detailed, quantitative information describing the relative abundance of selected noncellulosic polysaccharide linkages and primary structures. 28607074 6 54 theme specific 1194:1201 arg1 moieties 1250:1257 specific xylan, xyloglucan, pectin, and arabinogalactan moieties 1194:1257 specific xylan, xyloglucan, pectin, and arabinogalactan moieties 1194:1257 We undertook genome-wide association analysis of data collected from 57 carbohydrate microarrays and identified molecular markers reflecting a diversity of specific xylan, xyloglucan, pectin, and arabinogalactan moieties. 28607074 3 55 theme cell 497:500 arg1 synthesis 507:515 cell wall synthesis 497:515 cell wall synthesis 497:515 Association mapping is one of the few techniques that can help identify candidate genes without relying on our currently incomplete knowledge of cell wall synthesis. 28607074 6 56 theme pectin 1222:1227 arg1 moieties 1250:1257 specific xylan, xyloglucan, pectin, and arabinogalactan moieties 1194:1257 specific xylan, xyloglucan, pectin, and arabinogalactan moieties 1194:1257 We undertook genome-wide association analysis of data collected from 57 carbohydrate microarrays and identified molecular markers reflecting a diversity of specific xylan, xyloglucan, pectin, and arabinogalactan moieties. 28607074 6 57 theme xyloglucan 1210:1219 arg1 moieties 1250:1257 specific xylan, xyloglucan, pectin, and arabinogalactan moieties 1194:1257 specific xylan, xyloglucan, pectin, and arabinogalactan moieties 1194:1257 We undertook genome-wide association analysis of data collected from 57 carbohydrate microarrays and identified molecular markers reflecting a diversity of specific xylan, xyloglucan, pectin, and arabinogalactan moieties. 28607074 5 58 used used 875:878 arg2 we 700:701 we 700:701 we 700:701 Here, we created high-density carbohydrate microarrays containing chemically extracted cell wall polysaccharides collected from 331 genetically diverse Brassica napus cultivars and used them to obtain detailed, quantitative information describing the relative abundance of selected noncellulosic polysaccharide linkages and primary structures. 28607074 6 59 theme xylan 1203:1207 arg1 moieties 1250:1257 specific xylan, xyloglucan, pectin, and arabinogalactan moieties 1194:1257 specific xylan, xyloglucan, pectin, and arabinogalactan moieties 1194:1257 We undertook genome-wide association analysis of data collected from 57 carbohydrate microarrays and identified molecular markers reflecting a diversity of specific xylan, xyloglucan, pectin, and arabinogalactan moieties. 28607074 5 60 theme Brassica 846:853 arg1 cultivars 861:869 331 genetically diverse Brassica napus cultivars 822:869 331 genetically diverse Brassica napus cultivars 822:869 Here, we created high-density carbohydrate microarrays containing chemically extracted cell wall polysaccharides collected from 331 genetically diverse Brassica napus cultivars and used them to obtain detailed, quantitative information describing the relative abundance of selected noncellulosic polysaccharide linkages and primary structures. 28607074 8 61 theme functional 1536:1545 arg1 genomics 1547:1554 functional genomics 1536:1554 functional genomics 1536:1554 The identified markers also have value beyond B. napus for functional genomics, facilitated by the close genetic relatedness to the model plant Arabidopsis Together, our findings provide a unique dissection of the genetic architecture that underpins plant cell wall biosynthesis and restructuring. 28607074 4 62 theme cell 674:677 arg1 polymers 684:691 specific cell wall polymers 665:691 specific cell wall polymers 665:691 However, few cell wall phenotyping methodologies have proven sufficiently precise, robust, or scalable for association mapping to be conducted for specific cell wall polymers. 28607074 5 63 theme high-density 711:722 arg1 microarrays 737:747 high-density carbohydrate microarrays 711:747 high-density carbohydrate microarrays containing chemically extracted cell wall polysaccharides collected from 331 genetically diverse Brassica napus cultivars 711:869 Here, we created high-density carbohydrate microarrays containing chemically extracted cell wall polysaccharides collected from 331 genetically diverse Brassica napus cultivars and used them to obtain detailed, quantitative information describing the relative abundance of selected noncellulosic polysaccharide linkages and primary structures. 28607074 6 64 theme genome-wide 1051:1061 arg1 analysis 1075:1082 genome-wide association analysis 1051:1082 genome-wide association analysis of data collected from 57 carbohydrate microarrays 1051:1133 We undertook genome-wide association analysis of data collected from 57 carbohydrate microarrays and identified molecular markers reflecting a diversity of specific xylan, xyloglucan, pectin, and arabinogalactan moieties. 28607074 8 65 theme close 1576:1580 arg1 relatedness 1590:1600 the close genetic relatedness 1572:1600 the close genetic relatedness to the model plant Arabidopsis 1572:1631 The identified markers also have value beyond B. napus for functional genomics, facilitated by the close genetic relatedness to the model plant Arabidopsis Together, our findings provide a unique dissection of the genetic architecture that underpins plant cell wall biosynthesis and restructuring. 28607074 6 66 theme moieties 1250:1257 arg1 diversity 1181:1189 a diversity 1179:1189 a diversity of specific xylan, xyloglucan, pectin, and arabinogalactan moieties 1179:1257 We undertook genome-wide association analysis of data collected from 57 carbohydrate microarrays and identified molecular markers reflecting a diversity of specific xylan, xyloglucan, pectin, and arabinogalactan moieties. 28607074 1 67 theme cell 149:152 arg1 wall 154:157 the plant cell wall 139:157 the plant cell wall 139:157 Genetic improvement of the plant cell wall has enormous potential to increase the quality of food, fibers, and fuels. 28607074 2 68 dep identification 247:260 arg1 the 243:245 the 243:245 the 243:245 However, the identification and characterization of genes involved in plant cell wall synthesis is far from complete. 28607074 0 69 theme cell 93:96 arg1 composition 103:113 plant cell wall composition 87:113 plant cell wall composition 87:113 Carbohydrate microarrays and their use for the identification of molecular markers for plant cell wall composition. 28607074 5 70 theme noncellulosic 976:988 arg1 linkages 1005:1012 selected noncellulosic polysaccharide linkages 967:1012 selected noncellulosic polysaccharide linkages 967:1012 Here, we created high-density carbohydrate microarrays containing chemically extracted cell wall polysaccharides collected from 331 genetically diverse Brassica napus cultivars and used them to obtain detailed, quantitative information describing the relative abundance of selected noncellulosic polysaccharide linkages and primary structures. 28607074 5 71 theme linkages 1005:1012 arg1 abundance 954:962 the relative abundance 941:962 the relative abundance of selected noncellulosic polysaccharide linkages and primary structures 941:1035 Here, we created high-density carbohydrate microarrays containing chemically extracted cell wall polysaccharides collected from 331 genetically diverse Brassica napus cultivars and used them to obtain detailed, quantitative information describing the relative abundance of selected noncellulosic polysaccharide linkages and primary structures. 28607074 8 72 theme plant 1615:1619 arg1 Arabidopsis 1621:1631 the model plant Arabidopsis 1605:1631 the model plant Arabidopsis 1605:1631 The identified markers also have value beyond B. napus for functional genomics, facilitated by the close genetic relatedness to the model plant Arabidopsis Together, our findings provide a unique dissection of the genetic architecture that underpins plant cell wall biosynthesis and restructuring. 28607074 5 73 theme relative 945:952 arg1 abundance 954:962 the relative abundance 941:962 the relative abundance of selected noncellulosic polysaccharide linkages and primary structures 941:1035 Here, we created high-density carbohydrate microarrays containing chemically extracted cell wall polysaccharides collected from 331 genetically diverse Brassica napus cultivars and used them to obtain detailed, quantitative information describing the relative abundance of selected noncellulosic polysaccharide linkages and primary structures. 28607074 6 74 theme carbohydrate 1110:1121 arg1 microarrays 1123:1133 57 carbohydrate microarrays 1107:1133 57 carbohydrate microarrays 1107:1133 We undertook genome-wide association analysis of data collected from 57 carbohydrate microarrays and identified molecular markers reflecting a diversity of specific xylan, xyloglucan, pectin, and arabinogalactan moieties. 28607074 3 75 theme techniques 390:399 arg1 one 375:377 one 375:377 one 375:377 Association mapping is one of the few techniques that can help identify candidate genes without relying on our currently incomplete knowledge of cell wall synthesis. 28607074 3 75 theme techniques 390:399 arg1 techniques 390:399 the few techniques 382:399 the few techniques 382:399 Association mapping is one of the few techniques that can help identify candidate genes without relying on our currently incomplete knowledge of cell wall synthesis. 28607074 7 76 theme B. 1373:1374 arg1 genotypes 1382:1390 B. napus genotypes 1373:1390 B. napus genotypes 1373:1390 These datasets provide a detailed insight into the natural variations in cell wall carbohydrate moieties between B. napus genotypes and identify associated markers that could be exploited by marker-assisted breeding. 28607074 4 77 theme cell 531:534 arg1 methodologies 553:565 few cell wall phenotyping methodologies 527:565 few cell wall phenotyping methodologies 527:565 However, few cell wall phenotyping methodologies have proven sufficiently precise, robust, or scalable for association mapping to be conducted for specific cell wall polymers. 28607074 6 78 theme data 1087:1090 arg1 analysis 1075:1082 genome-wide association analysis 1051:1082 genome-wide association analysis of data collected from 57 carbohydrate microarrays 1051:1133 We undertook genome-wide association analysis of data collected from 57 carbohydrate microarrays and identified molecular markers reflecting a diversity of specific xylan, xyloglucan, pectin, and arabinogalactan moieties. 28607074 5 79 theme cell 781:784 arg1 polysaccharides 791:805 chemically extracted cell wall polysaccharides 760:805 chemically extracted cell wall polysaccharides collected from 331 genetically diverse Brassica napus cultivars 760:869 Here, we created high-density carbohydrate microarrays containing chemically extracted cell wall polysaccharides collected from 331 genetically diverse Brassica napus cultivars and used them to obtain detailed, quantitative information describing the relative abundance of selected noncellulosic polysaccharide linkages and primary structures. 28607074 7 80 theme wall 1338:1341 arg1 moieties 1356:1363 cell wall carbohydrate moieties 1333:1363 cell wall carbohydrate moieties 1333:1363 These datasets provide a detailed insight into the natural variations in cell wall carbohydrate moieties between B. napus genotypes and identify associated markers that could be exploited by marker-assisted breeding. 28607074 8 81 theme unique 1666:1671 arg1 dissection 1673:1682 a unique dissection 1664:1682 a unique dissection of the genetic architecture that underpins plant cell wall biosynthesis and restructuring 1664:1772 The identified markers also have value beyond B. napus for functional genomics, facilitated by the close genetic relatedness to the model plant Arabidopsis Together, our findings provide a unique dissection of the genetic architecture that underpins plant cell wall biosynthesis and restructuring. 28607074 8 82 theme identified 1481:1490 arg1 markers 1492:1498 The identified markers 1477:1498 The identified markers 1477:1498 The identified markers also have value beyond B. napus for functional genomics, facilitated by the close genetic relatedness to the model plant Arabidopsis Together, our findings provide a unique dissection of the genetic architecture that underpins plant cell wall biosynthesis and restructuring. 28607074 2 83 theme cell 310:313 arg1 synthesis 320:328 plant cell wall synthesis 304:328 plant cell wall synthesis 304:328 However, the identification and characterization of genes involved in plant cell wall synthesis is far from complete. 28607074 8 84 theme wall 1738:1741 arg1 biosynthesis 1743:1754 plant cell wall biosynthesis 1727:1754 plant cell wall biosynthesis 1727:1754 The identified markers also have value beyond B. napus for functional genomics, facilitated by the close genetic relatedness to the model plant Arabidopsis Together, our findings provide a unique dissection of the genetic architecture that underpins plant cell wall biosynthesis and restructuring. 28607074 5 85 theme primary 1018:1024 arg1 structures 1026:1035 primary structures 1018:1035 primary structures 1018:1035 Here, we created high-density carbohydrate microarrays containing chemically extracted cell wall polysaccharides collected from 331 genetically diverse Brassica napus cultivars and used them to obtain detailed, quantitative information describing the relative abundance of selected noncellulosic polysaccharide linkages and primary structures. 28607074 7 86 theme natural 1311:1317 arg1 variations 1319:1328 the natural variations 1307:1328 the natural variations in cell wall carbohydrate moieties between B. napus genotypes 1307:1390 These datasets provide a detailed insight into the natural variations in cell wall carbohydrate moieties between B. napus genotypes and identify associated markers that could be exploited by marker-assisted breeding. 28607074 8 87 theme genetic 1691:1697 arg1 architecture 1699:1710 the genetic architecture 1687:1710 the genetic architecture that underpins plant cell wall biosynthesis and restructuring 1687:1772 The identified markers also have value beyond B. napus for functional genomics, facilitated by the close genetic relatedness to the model plant Arabidopsis Together, our findings provide a unique dissection of the genetic architecture that underpins plant cell wall biosynthesis and restructuring. 25137044 12 0 theme vaccine 1439:1445 arg1 O157 1455:1458 glycoconjugate vaccine E. coli O157 1424:1458 glycoconjugate vaccine E. coli O157:H7-specific O-Ag-MBP produced by bacterial protein N-linked glycosylation system was able to elicit both humoral and Th1-biased cellular responses. 1424:1606 Thus, glycoconjugate vaccine E. coli O157:H7-specific O-Ag-MBP produced by bacterial protein N-linked glycosylation system was able to elicit both humoral and Th1-biased cellular responses. 25137044 11 1 theme Th1 1376:1378 arg1 cells 1380:1384 Th1 cells 1376:1384 Th1 cells 1376:1384 MBP showed TLR4 agonist-like properties to activate Th1 cells as carrier protein of O-Ag-MBP. 25137044 4 2 theme maltose-binding 606:620 arg1 protein 622:628 maltose-binding protein 606:628 maltose-binding protein 606:628 In this study, we exploited a novel approach based on bacterial protein N-linked glycosylation system to produce glycoconjugate containing Escherichia coli O157:H7 O-antigen linked with maltose-binding protein and examined its humoral and cellular responses in BALB/c mice. 25137044 11 3 theme O-Ag-MBP 1408:1415 arg1 protein 1397:1403 carrier protein 1389:1403 carrier protein of O-Ag-MBP 1389:1415 MBP showed TLR4 agonist-like properties to activate Th1 cells as carrier protein of O-Ag-MBP. 25137044 4 4 dep exploited 438:446 arg1 produce 525:531 produce 525:531 to produce glycoconjugate containing Escherichia coli O157:H7 O-antigen linked with maltose-binding protein 522:628 In this study, we exploited a novel approach based on bacterial protein N-linked glycosylation system to produce glycoconjugate containing Escherichia coli O157:H7 O-antigen linked with maltose-binding protein and examined its humoral and cellular responses in BALB/c mice. 25137044 4 4 dep exploited 438:446 arg1 examined 634:641 examined 634:641 examined its humoral and cellular responses in BALB/c mice 634:691 In this study, we exploited a novel approach based on bacterial protein N-linked glycosylation system to produce glycoconjugate containing Escherichia coli O157:H7 O-antigen linked with maltose-binding protein and examined its humoral and cellular responses in BALB/c mice. 25137044 6 5 theme H7 901:902 arg1 O-antigen 904:912 H7 O-antigen IgG and IgM 901:924 coli O157:H7 O-antigen IgG and IgM. 891:925 coli O157:H7 O-antigen IgG and IgM. 25137044 8 6 theme coli 992:995 arg1 O157 997:1000 coli O157 992:1000 coli O157:H7 O-antigen IgA in intestine. 992:1031 coli O157:H7 O-antigen IgA in intestine. 25137044 4 7 theme BALB/c 681:686 arg1 mice 688:691 BALB/c mice 681:691 BALB/c mice 681:691 In this study, we exploited a novel approach based on bacterial protein N-linked glycosylation system to produce glycoconjugate containing Escherichia coli O157:H7 O-antigen linked with maltose-binding protein and examined its humoral and cellular responses in BALB/c mice. 25137044 2 8 theme coli 296:299 arg1 O157 301:304 pathogen E. coli O157 284:304 pathogen E. coli O157:H7 284:307 Previous studies of glycoconjugates against pathogen E. coli O157:H7 focused more on the humoral responses they elicited. 25137044 1 9 theme efficacious 179:189 arg1 vaccines 202:209 the most efficacious and safest vaccines 170:209 the most efficacious and safest vaccines against bacterial pathogens 170:237 Glycoconjugate is one of the most efficacious and safest vaccines against bacterial pathogens. 25137044 1 10 theme safest 195:200 arg1 vaccines 202:209 the most efficacious and safest vaccines 170:209 the most efficacious and safest vaccines against bacterial pathogens 170:237 Glycoconjugate is one of the most efficacious and safest vaccines against bacterial pathogens. 25137044 8 11 theme O-antigen 1005:1013 arg1 IgA 1015:1017 H7 O-antigen IgA 1002:1017 coli O157:H7 O-antigen IgA in intestine. 992:1031 coli O157:H7 O-antigen IgA in intestine. 25137044 10 12 theme Th1-related 1186:1196 arg1 IFN-γ 1198:1202 Th1-related IFN-γ 1186:1202 Th1-related IFN-γ 1186:1202 Meanwhile, O-Ag-MBP induced the upregulation of Th1-related IFN-γ and downregulation of Th2-related IL-4, and the upregulation of IFN-γ was stimulated by MBP in a dose-dependent manner. 25137044 5 13 theme O157 718:721 arg1 O-antigen 726:734 E. coli O157:H7 O-antigen 710:734 E. coli O157:H7 O-antigen 710:734 The transfer of E. coli O157:H7 O-antigen to MBP was confirmed by western blot and MALDI-TOF MS. Mice injected with glycoconjugate O-Ag-MBP elicited serum bactericidal antibodies including anti-E. 25137044 5 14 theme serum 843:847 arg1 anti-E 883:888 anti-E 883:888 anti-E 883:888 The transfer of E. coli O157:H7 O-antigen to MBP was confirmed by western blot and MALDI-TOF MS. Mice injected with glycoconjugate O-Ag-MBP elicited serum bactericidal antibodies including anti-E. 25137044 5 14 theme serum 843:847 arg1 antibodies 862:871 serum bactericidal antibodies 843:871 serum bactericidal antibodies including anti-E 843:888 The transfer of E. coli O157:H7 O-antigen to MBP was confirmed by western blot and MALDI-TOF MS. Mice injected with glycoconjugate O-Ag-MBP elicited serum bactericidal antibodies including anti-E. 25137044 4 15 link N-linked 492:499 arg1 system 515:520 bacterial protein N-linked glycosylation system 474:520 bacterial protein N-linked glycosylation system 474:520 In this study, we exploited a novel approach based on bacterial protein N-linked glycosylation system to produce glycoconjugate containing Escherichia coli O157:H7 O-antigen linked with maltose-binding protein and examined its humoral and cellular responses in BALB/c mice. 25137044 12 16 dep O157 1455:1458 arg1 able 1545:1548 able 1545:1548 able 1545:1548 Thus, glycoconjugate vaccine E. coli O157:H7-specific O-Ag-MBP produced by bacterial protein N-linked glycosylation system was able to elicit both humoral and Th1-biased cellular responses. 25137044 5 17 theme glycoconjugate 810:823 arg1 O-Ag-MBP 825:832 glycoconjugate O-Ag-MBP 810:832 glycoconjugate O-Ag-MBP 810:832 The transfer of E. coli O157:H7 O-antigen to MBP was confirmed by western blot and MALDI-TOF MS. Mice injected with glycoconjugate O-Ag-MBP elicited serum bactericidal antibodies including anti-E. 25137044 4 18 theme novel 450:454 arg1 approach 456:463 a novel approach 448:463 a novel approach based on bacterial protein N-linked glycosylation system 448:520 In this study, we exploited a novel approach based on bacterial protein N-linked glycosylation system to produce glycoconjugate containing Escherichia coli O157:H7 O-antigen linked with maltose-binding protein and examined its humoral and cellular responses in BALB/c mice. 25137044 12 19 link N-linked 1511:1518 arg1 system 1534:1539 bacterial protein N-linked glycosylation system 1493:1539 bacterial protein N-linked glycosylation system 1493:1539 Thus, glycoconjugate vaccine E. coli O157:H7-specific O-Ag-MBP produced by bacterial protein N-linked glycosylation system was able to elicit both humoral and Th1-biased cellular responses. 25137044 11 20 theme agonist-like 1340:1351 arg1 properties 1353:1362 TLR4 agonist-like properties 1335:1362 TLR4 agonist-like properties 1335:1362 MBP showed TLR4 agonist-like properties to activate Th1 cells as carrier protein of O-Ag-MBP. 25137044 12 21 dep E. 1447:1448 arg1 coli 1450:1453 coli 1450:1453 coli 1450:1453 Thus, glycoconjugate vaccine E. coli O157:H7-specific O-Ag-MBP produced by bacterial protein N-linked glycosylation system was able to elicit both humoral and Th1-biased cellular responses. 25137044 12 22 theme cellular 1588:1595 arg1 responses 1597:1605 both humoral and Th1-biased cellular responses 1560:1605 both humoral and Th1-biased cellular responses 1560:1605 Thus, glycoconjugate vaccine E. coli O157:H7-specific O-Ag-MBP produced by bacterial protein N-linked glycosylation system was able to elicit both humoral and Th1-biased cellular responses. 25137044 10 23 theme IL-4 1238:1241 arg1 upregulation 1170:1181 the upregulation 1166:1181 the upregulation of Th1-related IFN-γ 1166:1202 Meanwhile, O-Ag-MBP induced the upregulation of Th1-related IFN-γ and downregulation of Th2-related IL-4, and the upregulation of IFN-γ was stimulated by MBP in a dose-dependent manner. 25137044 10 23 theme IL-4 1238:1241 arg1 downregulation 1208:1221 downregulation 1208:1221 downregulation of Th2-related IL-4 1208:1241 Meanwhile, O-Ag-MBP induced the upregulation of Th1-related IFN-γ and downregulation of Th2-related IL-4, and the upregulation of IFN-γ was stimulated by MBP in a dose-dependent manner. 25137044 5 24 theme E. 710:711 arg1 O157 718:721 E. coli O157 710:721 E. coli O157:H7 O-antigen 710:734 The transfer of E. coli O157:H7 O-antigen to MBP was confirmed by western blot and MALDI-TOF MS. Mice injected with glycoconjugate O-Ag-MBP elicited serum bactericidal antibodies including anti-E. 25137044 2 25 theme pathogen 284:291 arg1 O157 301:304 pathogen E. coli O157 284:304 pathogen E. coli O157:H7 284:307 Previous studies of glycoconjugates against pathogen E. coli O157:H7 focused more on the humoral responses they elicited. 25137044 2 26 dep O157 301:304 arg1 H7 306:307 H7 306:307 pathogen E. coli O157:H7 284:307 Previous studies of glycoconjugates against pathogen E. coli O157:H7 focused more on the humoral responses they elicited. 25137044 4 27 dep Escherichia 559:569 arg1 coli 571:574 coli 571:574 coli 571:574 In this study, we exploited a novel approach based on bacterial protein N-linked glycosylation system to produce glycoconjugate containing Escherichia coli O157:H7 O-antigen linked with maltose-binding protein and examined its humoral and cellular responses in BALB/c mice. 25137044 2 28 theme glycoconjugates 260:274 arg1 studies 249:255 Previous studies 240:255 Previous studies of glycoconjugates against pathogen E. coli O157:H7 240:307 Previous studies of glycoconjugates against pathogen E. coli O157:H7 focused more on the humoral responses they elicited. 25137044 7 29 theme anti-E 984:989 arg1 secretion 971:979 the secretion 967:979 the secretion of anti-E 967:989 Interestingly, O-Ag-MBP also stimulated the secretion of anti-E. 25137044 4 30 theme N-linked 492:499 arg1 system 515:520 bacterial protein N-linked glycosylation system 474:520 bacterial protein N-linked glycosylation system 474:520 In this study, we exploited a novel approach based on bacterial protein N-linked glycosylation system to produce glycoconjugate containing Escherichia coli O157:H7 O-antigen linked with maltose-binding protein and examined its humoral and cellular responses in BALB/c mice. 25137044 12 31 theme glycosylation 1520:1532 arg1 system 1534:1539 bacterial protein N-linked glycosylation system 1493:1539 bacterial protein N-linked glycosylation system 1493:1539 Thus, glycoconjugate vaccine E. coli O157:H7-specific O-Ag-MBP produced by bacterial protein N-linked glycosylation system was able to elicit both humoral and Th1-biased cellular responses. 25137044 4 32 dep H7 581:582 arg1 O-antigen 584:592 O-antigen 584:592 Escherichia coli O157:H7 O-antigen linked with maltose-binding protein 559:628 In this study, we exploited a novel approach based on bacterial protein N-linked glycosylation system to produce glycoconjugate containing Escherichia coli O157:H7 O-antigen linked with maltose-binding protein and examined its humoral and cellular responses in BALB/c mice. 25137044 0 33 theme humoral 113:119 arg1 responses 134:142 humoral and cellular responses 113:142 humoral and cellular responses 113:142 Glycoconjugate vaccine containing Escherichia coli O157:H7 O-antigen linked with maltose-binding protein elicits humoral and cellular responses. 25137044 4 34 dep O157 576:579 arg1 H7 581:582 H7 581:582 Escherichia coli O157:H7 O-antigen linked with maltose-binding protein 559:628 In this study, we exploited a novel approach based on bacterial protein N-linked glycosylation system to produce glycoconjugate containing Escherichia coli O157:H7 O-antigen linked with maltose-binding protein and examined its humoral and cellular responses in BALB/c mice. 25137044 4 35 theme bacterial 474:482 arg1 system 515:520 bacterial protein N-linked glycosylation system 474:520 bacterial protein N-linked glycosylation system 474:520 In this study, we exploited a novel approach based on bacterial protein N-linked glycosylation system to produce glycoconjugate containing Escherichia coli O157:H7 O-antigen linked with maltose-binding protein and examined its humoral and cellular responses in BALB/c mice. 25137044 2 36 dep responses 337:345 arg1 they 347:350 they 347:350 they 347:350 Previous studies of glycoconjugates against pathogen E. coli O157:H7 focused more on the humoral responses they elicited. 25137044 10 37 theme IFN-γ 1268:1272 arg1 upregulation 1252:1263 the upregulation 1248:1263 the upregulation of IFN-γ 1248:1272 Meanwhile, O-Ag-MBP induced the upregulation of Th1-related IFN-γ and downregulation of Th2-related IL-4, and the upregulation of IFN-γ was stimulated by MBP in a dose-dependent manner. 25137044 0 38 theme Glycoconjugate 0:13 arg1 O157 51:54 Glycoconjugate vaccine containing Escherichia coli O157 0:54 Glycoconjugate vaccine containing Escherichia coli O157:H7 O-antigen linked with maltose-binding protein elicits humoral and cellular responses. 0:143 Glycoconjugate vaccine containing Escherichia coli O157:H7 O-antigen linked with maltose-binding protein elicits humoral and cellular responses. 25137044 9 39 theme CD4+ 1110:1113 arg1 cells 1131:1135 CD8+ T cells 1124:1135 CD8+ T cells 1124:1135 In addition, O-Ag-MBP stimulated cellular responses by recruiting Th1-biased CD4+ T cells, CD8+ T cells. 25137044 9 39 theme CD4+ 1110:1113 arg1 cells 1117:1121 Th1-biased CD4+ T cells 1099:1121 Th1-biased CD4+ T cells 1099:1121 In addition, O-Ag-MBP stimulated cellular responses by recruiting Th1-biased CD4+ T cells, CD8+ T cells. 25137044 0 40 theme containing 23:32 arg1 O157 51:54 Glycoconjugate vaccine containing Escherichia coli O157 0:54 Glycoconjugate vaccine containing Escherichia coli O157:H7 O-antigen linked with maltose-binding protein elicits humoral and cellular responses. 0:143 Glycoconjugate vaccine containing Escherichia coli O157:H7 O-antigen linked with maltose-binding protein elicits humoral and cellular responses. 25137044 6 41 theme coli 891:894 arg1 O157 896:899 coli O157 891:899 coli O157:H7 O-antigen IgG and IgM. 891:925 coli O157:H7 O-antigen IgG and IgM. 25137044 12 42 theme N-linked 1511:1518 arg1 system 1534:1539 bacterial protein N-linked glycosylation system 1493:1539 bacterial protein N-linked glycosylation system 1493:1539 Thus, glycoconjugate vaccine E. coli O157:H7-specific O-Ag-MBP produced by bacterial protein N-linked glycosylation system was able to elicit both humoral and Th1-biased cellular responses. 25137044 3 43 theme cellular 400:407 arg1 responses 409:417 their cellular responses 394:417 their cellular responses 394:417 However, little was known about their cellular responses. 25137044 9 44 theme CD8+ 1124:1127 arg1 cells 1131:1135 CD8+ T cells 1124:1135 CD8+ T cells 1124:1135 In addition, O-Ag-MBP stimulated cellular responses by recruiting Th1-biased CD4+ T cells, CD8+ T cells. 25137044 9 44 theme CD8+ 1124:1127 arg1 cells 1117:1121 Th1-biased CD4+ T cells 1099:1121 Th1-biased CD4+ T cells 1099:1121 In addition, O-Ag-MBP stimulated cellular responses by recruiting Th1-biased CD4+ T cells, CD8+ T cells. 25137044 12 45 theme H7-specific 1460:1470 arg1 O-Ag-MBP 1472:1479 H7-specific O-Ag-MBP 1460:1479 H7-specific O-Ag-MBP produced by bacterial protein N-linked glycosylation system 1460:1539 Thus, glycoconjugate vaccine E. coli O157:H7-specific O-Ag-MBP produced by bacterial protein N-linked glycosylation system was able to elicit both humoral and Th1-biased cellular responses. 25137044 9 46 theme Th1-biased 1099:1108 arg1 cells 1131:1135 CD8+ T cells 1124:1135 CD8+ T cells 1124:1135 In addition, O-Ag-MBP stimulated cellular responses by recruiting Th1-biased CD4+ T cells, CD8+ T cells. 25137044 9 46 theme Th1-biased 1099:1108 arg1 cells 1117:1121 Th1-biased CD4+ T cells 1099:1121 Th1-biased CD4+ T cells 1099:1121 In addition, O-Ag-MBP stimulated cellular responses by recruiting Th1-biased CD4+ T cells, CD8+ T cells. 25137044 6 47 dep O157 896:899 arg1 O-antigen 904:912 H7 O-antigen IgG and IgM 901:924 coli O157:H7 O-antigen IgG and IgM. 891:925 coli O157:H7 O-antigen IgG and IgM. 25137044 12 48 theme E. 1447:1448 arg1 O157 1455:1458 glycoconjugate vaccine E. coli O157 1424:1458 glycoconjugate vaccine E. coli O157:H7-specific O-Ag-MBP produced by bacterial protein N-linked glycosylation system was able to elicit both humoral and Th1-biased cellular responses. 1424:1606 Thus, glycoconjugate vaccine E. coli O157:H7-specific O-Ag-MBP produced by bacterial protein N-linked glycosylation system was able to elicit both humoral and Th1-biased cellular responses. 25137044 5 49 theme western 760:766 arg1 blot 768:771 western blot 760:771 western blot 760:771 The transfer of E. coli O157:H7 O-antigen to MBP was confirmed by western blot and MALDI-TOF MS. Mice injected with glycoconjugate O-Ag-MBP elicited serum bactericidal antibodies including anti-E. 25137044 4 50 contain containing 548:557 arg2 O157 576:579 Escherichia coli O157 559:579 Escherichia coli O157:H7 O-antigen linked with maltose-binding protein 559:628 In this study, we exploited a novel approach based on bacterial protein N-linked glycosylation system to produce glycoconjugate containing Escherichia coli O157:H7 O-antigen linked with maltose-binding protein and examined its humoral and cellular responses in BALB/c mice. 25137044 4 50 contain containing 548:557 arg1 glycoconjugate 533:546 glycoconjugate 533:546 glycoconjugate containing Escherichia coli O157:H7 O-antigen linked with maltose-binding protein 533:628 In this study, we exploited a novel approach based on bacterial protein N-linked glycosylation system to produce glycoconjugate containing Escherichia coli O157:H7 O-antigen linked with maltose-binding protein and examined its humoral and cellular responses in BALB/c mice. 25137044 10 51 theme IFN-γ 1198:1202 arg1 upregulation 1170:1181 the upregulation 1166:1181 the upregulation of Th1-related IFN-γ 1166:1202 Meanwhile, O-Ag-MBP induced the upregulation of Th1-related IFN-γ and downregulation of Th2-related IL-4, and the upregulation of IFN-γ was stimulated by MBP in a dose-dependent manner. 25137044 10 51 theme IFN-γ 1198:1202 arg1 downregulation 1208:1221 downregulation 1208:1221 downregulation of Th2-related IL-4 1208:1241 Meanwhile, O-Ag-MBP induced the upregulation of Th1-related IFN-γ and downregulation of Th2-related IL-4, and the upregulation of IFN-γ was stimulated by MBP in a dose-dependent manner. 25137044 11 52 theme carrier 1389:1395 arg1 protein 1397:1403 carrier protein 1389:1403 carrier protein of O-Ag-MBP 1389:1415 MBP showed TLR4 agonist-like properties to activate Th1 cells as carrier protein of O-Ag-MBP. 25137044 1 53 theme most 174:177 arg1 vaccines 202:209 the most efficacious and safest vaccines 170:209 the most efficacious and safest vaccines against bacterial pathogens 170:237 Glycoconjugate is one of the most efficacious and safest vaccines against bacterial pathogens. 25137044 12 54 theme glycoconjugate 1424:1437 arg1 O157 1455:1458 glycoconjugate vaccine E. coli O157 1424:1458 glycoconjugate vaccine E. coli O157:H7-specific O-Ag-MBP produced by bacterial protein N-linked glycosylation system was able to elicit both humoral and Th1-biased cellular responses. 1424:1606 Thus, glycoconjugate vaccine E. coli O157:H7-specific O-Ag-MBP produced by bacterial protein N-linked glycosylation system was able to elicit both humoral and Th1-biased cellular responses. 25137044 8 55 theme H7 1002:1003 arg1 IgA 1015:1017 H7 O-antigen IgA 1002:1017 coli O157:H7 O-antigen IgA in intestine. 992:1031 coli O157:H7 O-antigen IgA in intestine. 25137044 1 56 theme vaccines 202:209 arg1 one 163:165 one 163:165 one 163:165 Glycoconjugate is one of the most efficacious and safest vaccines against bacterial pathogens. 25137044 1 56 theme vaccines 202:209 arg1 vaccines 202:209 the most efficacious and safest vaccines 170:209 the most efficacious and safest vaccines against bacterial pathogens 170:237 Glycoconjugate is one of the most efficacious and safest vaccines against bacterial pathogens. 25137044 4 57 theme humoral 647:653 arg1 responses 668:676 its humoral and cellular responses 643:676 its humoral and cellular responses 643:676 In this study, we exploited a novel approach based on bacterial protein N-linked glycosylation system to produce glycoconjugate containing Escherichia coli O157:H7 O-antigen linked with maltose-binding protein and examined its humoral and cellular responses in BALB/c mice. 25137044 5 58 theme bactericidal 849:860 arg1 anti-E 883:888 anti-E 883:888 anti-E 883:888 The transfer of E. coli O157:H7 O-antigen to MBP was confirmed by western blot and MALDI-TOF MS. Mice injected with glycoconjugate O-Ag-MBP elicited serum bactericidal antibodies including anti-E. 25137044 5 58 theme bactericidal 849:860 arg1 antibodies 862:871 serum bactericidal antibodies 843:871 serum bactericidal antibodies including anti-E 843:888 The transfer of E. coli O157:H7 O-antigen to MBP was confirmed by western blot and MALDI-TOF MS. Mice injected with glycoconjugate O-Ag-MBP elicited serum bactericidal antibodies including anti-E. 25137044 12 59 theme Th1-biased 1577:1586 arg1 responses 1597:1605 both humoral and Th1-biased cellular responses 1560:1605 both humoral and Th1-biased cellular responses 1560:1605 Thus, glycoconjugate vaccine E. coli O157:H7-specific O-Ag-MBP produced by bacterial protein N-linked glycosylation system was able to elicit both humoral and Th1-biased cellular responses. 25137044 4 60 theme cellular 659:666 arg1 responses 668:676 its humoral and cellular responses 643:676 its humoral and cellular responses 643:676 In this study, we exploited a novel approach based on bacterial protein N-linked glycosylation system to produce glycoconjugate containing Escherichia coli O157:H7 O-antigen linked with maltose-binding protein and examined its humoral and cellular responses in BALB/c mice. 25137044 11 61 theme TLR4 1335:1338 arg1 properties 1353:1362 TLR4 agonist-like properties 1335:1362 TLR4 agonist-like properties 1335:1362 MBP showed TLR4 agonist-like properties to activate Th1 cells as carrier protein of O-Ag-MBP. 25137044 2 62 theme Previous 240:247 arg1 studies 249:255 Previous studies 240:255 Previous studies of glycoconjugates against pathogen E. coli O157:H7 240:307 Previous studies of glycoconjugates against pathogen E. coli O157:H7 focused more on the humoral responses they elicited. 25137044 2 63 theme E. 293:294 arg1 O157 301:304 pathogen E. coli O157 284:304 pathogen E. coli O157:H7 284:307 Previous studies of glycoconjugates against pathogen E. coli O157:H7 focused more on the humoral responses they elicited. 25137044 10 64 theme Th2-related 1226:1236 arg1 IL-4 1238:1241 Th2-related IL-4 1226:1241 Th2-related IL-4 1226:1241 Meanwhile, O-Ag-MBP induced the upregulation of Th1-related IFN-γ and downregulation of Th2-related IL-4, and the upregulation of IFN-γ was stimulated by MBP in a dose-dependent manner. 25137044 10 65 theme dose-dependent 1301:1314 arg1 manner 1316:1321 a dose-dependent manner 1299:1321 a dose-dependent manner 1299:1321 Meanwhile, O-Ag-MBP induced the upregulation of Th1-related IFN-γ and downregulation of Th2-related IL-4, and the upregulation of IFN-γ was stimulated by MBP in a dose-dependent manner. 25137044 12 66 theme humoral 1565:1571 arg1 responses 1597:1605 both humoral and Th1-biased cellular responses 1560:1605 both humoral and Th1-biased cellular responses 1560:1605 Thus, glycoconjugate vaccine E. coli O157:H7-specific O-Ag-MBP produced by bacterial protein N-linked glycosylation system was able to elicit both humoral and Th1-biased cellular responses. 25137044 4 67 theme glycosylation 501:513 arg1 system 515:520 bacterial protein N-linked glycosylation system 474:520 bacterial protein N-linked glycosylation system 474:520 In this study, we exploited a novel approach based on bacterial protein N-linked glycosylation system to produce glycoconjugate containing Escherichia coli O157:H7 O-antigen linked with maltose-binding protein and examined its humoral and cellular responses in BALB/c mice. 25137044 0 68 theme maltose-binding 81:95 arg1 protein 97:103 maltose-binding protein 81:103 maltose-binding protein 81:103 Glycoconjugate vaccine containing Escherichia coli O157:H7 O-antigen linked with maltose-binding protein elicits humoral and cellular responses. 25137044 5 69 dep O157 718:721 arg1 H7 723:724 H7 723:724 E. coli O157:H7 O-antigen 710:734 The transfer of E. coli O157:H7 O-antigen to MBP was confirmed by western blot and MALDI-TOF MS. Mice injected with glycoconjugate O-Ag-MBP elicited serum bactericidal antibodies including anti-E. 25137044 5 70 theme O-antigen 726:734 arg1 transfer 698:705 The transfer 694:705 The transfer of E. coli O157:H7 O-antigen to MBP 694:741 The transfer of E. coli O157:H7 O-antigen to MBP was confirmed by western blot and MALDI-TOF MS. Mice injected with glycoconjugate O-Ag-MBP elicited serum bactericidal antibodies including anti-E. 25137044 5 71 dep E. 710:711 arg1 coli 713:716 coli 713:716 coli 713:716 The transfer of E. coli O157:H7 O-antigen to MBP was confirmed by western blot and MALDI-TOF MS. Mice injected with glycoconjugate O-Ag-MBP elicited serum bactericidal antibodies including anti-E. 25137044 9 72 theme cellular 1066:1073 arg1 responses 1075:1083 cellular responses 1066:1083 cellular responses 1066:1083 In addition, O-Ag-MBP stimulated cellular responses by recruiting Th1-biased CD4+ T cells, CD8+ T cells. 25137044 4 73 theme protein 484:490 arg1 system 515:520 bacterial protein N-linked glycosylation system 474:520 bacterial protein N-linked glycosylation system 474:520 In this study, we exploited a novel approach based on bacterial protein N-linked glycosylation system to produce glycoconjugate containing Escherichia coli O157:H7 O-antigen linked with maltose-binding protein and examined its humoral and cellular responses in BALB/c mice. 25137044 0 74 theme vaccine 15:21 arg1 O157 51:54 Glycoconjugate vaccine containing Escherichia coli O157 0:54 Glycoconjugate vaccine containing Escherichia coli O157:H7 O-antigen linked with maltose-binding protein elicits humoral and cellular responses. 0:143 Glycoconjugate vaccine containing Escherichia coli O157:H7 O-antigen linked with maltose-binding protein elicits humoral and cellular responses. 25137044 8 75 dep O157 997:1000 arg1 IgA 1015:1017 H7 O-antigen IgA 1002:1017 coli O157:H7 O-antigen IgA in intestine. 992:1031 coli O157:H7 O-antigen IgA in intestine. 25137044 0 76 theme Escherichia 34:44 arg1 O157 51:54 Glycoconjugate vaccine containing Escherichia coli O157 0:54 Glycoconjugate vaccine containing Escherichia coli O157:H7 O-antigen linked with maltose-binding protein elicits humoral and cellular responses. 0:143 Glycoconjugate vaccine containing Escherichia coli O157:H7 O-antigen linked with maltose-binding protein elicits humoral and cellular responses. 25137044 9 77 theme T 1115:1115 arg1 cells 1131:1135 CD8+ T cells 1124:1135 CD8+ T cells 1124:1135 In addition, O-Ag-MBP stimulated cellular responses by recruiting Th1-biased CD4+ T cells, CD8+ T cells. 25137044 9 77 theme T 1115:1115 arg1 cells 1117:1121 Th1-biased CD4+ T cells 1099:1121 Th1-biased CD4+ T cells 1099:1121 In addition, O-Ag-MBP stimulated cellular responses by recruiting Th1-biased CD4+ T cells, CD8+ T cells. 25137044 8 78 from IgA 1015:1017 arg1 intestine 1022:1030 intestine 1022:1030 intestine 1022:1030 coli O157:H7 O-antigen IgA in intestine. 25137044 12 79 theme bacterial 1493:1501 arg1 system 1534:1539 bacterial protein N-linked glycosylation system 1493:1539 bacterial protein N-linked glycosylation system 1493:1539 Thus, glycoconjugate vaccine E. coli O157:H7-specific O-Ag-MBP produced by bacterial protein N-linked glycosylation system was able to elicit both humoral and Th1-biased cellular responses. 25137044 1 80 theme bacterial 219:227 arg1 pathogens 229:237 bacterial pathogens 219:237 bacterial pathogens 219:237 Glycoconjugate is one of the most efficacious and safest vaccines against bacterial pathogens. 25137044 0 81 theme H7 56:57 arg1 O-antigen 59:67 H7 O-antigen 56:67 H7 O-antigen linked with maltose-binding protein 56:103 Glycoconjugate vaccine containing Escherichia coli O157:H7 O-antigen linked with maltose-binding protein elicits humoral and cellular responses. 25137044 12 82 theme protein 1503:1509 arg1 system 1534:1539 bacterial protein N-linked glycosylation system 1493:1539 bacterial protein N-linked glycosylation system 1493:1539 Thus, glycoconjugate vaccine E. coli O157:H7-specific O-Ag-MBP produced by bacterial protein N-linked glycosylation system was able to elicit both humoral and Th1-biased cellular responses. 25137044 0 83 dep O157 51:54 arg1 elicits 105:111 elicits 105:111 elicits humoral and cellular responses 105:142 Glycoconjugate vaccine containing Escherichia coli O157:H7 O-antigen linked with maltose-binding protein elicits humoral and cellular responses. 25137044 4 84 theme Escherichia 559:569 arg1 O157 576:579 Escherichia coli O157 559:579 Escherichia coli O157:H7 O-antigen linked with maltose-binding protein 559:628 In this study, we exploited a novel approach based on bacterial protein N-linked glycosylation system to produce glycoconjugate containing Escherichia coli O157:H7 O-antigen linked with maltose-binding protein and examined its humoral and cellular responses in BALB/c mice. 25137044 9 85 theme T 1129:1129 arg1 cells 1131:1135 CD8+ T cells 1124:1135 CD8+ T cells 1124:1135 In addition, O-Ag-MBP stimulated cellular responses by recruiting Th1-biased CD4+ T cells, CD8+ T cells. 25137044 9 85 theme T 1129:1129 arg1 cells 1117:1121 Th1-biased CD4+ T cells 1099:1121 Th1-biased CD4+ T cells 1099:1121 In addition, O-Ag-MBP stimulated cellular responses by recruiting Th1-biased CD4+ T cells, CD8+ T cells. 25137044 0 86 dep Escherichia 34:44 arg1 coli 46:49 coli 46:49 coli 46:49 Glycoconjugate vaccine containing Escherichia coli O157:H7 O-antigen linked with maltose-binding protein elicits humoral and cellular responses. 25137044 2 87 theme humoral 329:335 arg1 responses 337:345 the humoral responses 325:345 the humoral responses they elicited 325:359 Previous studies of glycoconjugates against pathogen E. coli O157:H7 focused more on the humoral responses they elicited. 25137044 0 88 theme cellular 125:132 arg1 responses 134:142 humoral and cellular responses 113:142 humoral and cellular responses 113:142 Glycoconjugate vaccine containing Escherichia coli O157:H7 O-antigen linked with maltose-binding protein elicits humoral and cellular responses. 25137044 6 89 dep O-antigen 904:912 arg1 IgM 922:924 IgM 922:924 IgM 922:924 coli O157:H7 O-antigen IgG and IgM. 25137044 6 89 dep O-antigen 904:912 arg1 IgG 914:916 IgG 914:916 IgG 914:916 coli O157:H7 O-antigen IgG and IgM. 24531716 7 0 theme cells 988:992 arg1 phenotype 948:956 the MDR phenotype changing 940:965 the MDR phenotype changing of HL60 and HL60/ADR cells both in vitro and in vivo 940:1018 The altered levels of ST3GAL5 and ST8SIA4 were found in close association with the MDR phenotype changing of HL60 and HL60/ADR cells both in vitro and in vivo. 24531716 6 1 theme ST8SIA4 762:768 arg1 levels 740:745 The expression levels 725:745 The expression levels of ST3GAL5 and ST8SIA4 725:768 The expression levels of ST3GAL5 and ST8SIA4 were detected, which were overexpressed in HL60 and HL60/adriamycin-resistant (ADR) cells. 24531716 4 2 gly sialylated 480:489 arg1 N-glycans 491:499 sialylated N-glycans 480:499 sialylated N-glycans 480:499 Using mass spectrometry (MS) analysis, the composition profiling of sialylated N-glycans differed in three pairs of AML cell lines. 24531716 6 3 theme ST3GAL5 750:756 arg1 levels 740:745 The expression levels 725:745 The expression levels of ST3GAL5 and ST8SIA4 725:768 The expression levels of ST3GAL5 and ST8SIA4 were detected, which were overexpressed in HL60 and HL60/adriamycin-resistant (ADR) cells. 24531716 2 4 theme resistance 276:285 arg1 regulation 245:254 sialylation regulation 233:254 sialylation regulation of cancer multidrug resistance (MDR) 233:291 However, the role of sialylation regulation of cancer multidrug resistance (MDR) remains poorly understood. 24531716 1 5 theme tumor 178:182 arg1 progression 184:194 tumor progression 178:194 tumor progression 178:194 Aberrant cell surface sialylation patterns have been shown to correlate with tumor progression and metastasis. 24531716 8 6 theme phosphoinositide-3 1122:1139 arg1 pathway 1169:1175 phosphoinositide-3 kinase (PI3K)/Akt signaling pathway 1122:1175 phosphoinositide-3 kinase (PI3K)/Akt signaling pathway 1122:1175 Further data demonstrated that manipulation of these two genes' expression modulated the activity of phosphoinositide-3 kinase (PI3K)/Akt signaling pathway and its downstream target thus regulated the proportionally mutative expression of P-glycoprotein (P-gp) and MDR-related protein 1 (MRP1), both of which are known to be involved in MDR. 24531716 8 7 theme downstream 1185:1194 arg1 target 1196:1201 its downstream target 1181:1201 its downstream target 1181:1201 Further data demonstrated that manipulation of these two genes' expression modulated the activity of phosphoinositide-3 kinase (PI3K)/Akt signaling pathway and its downstream target thus regulated the proportionally mutative expression of P-glycoprotein (P-gp) and MDR-related protein 1 (MRP1), both of which are known to be involved in MDR. 24531716 5 8 theme marrow 675:680 arg1 BMMCs 701:705 BMMCs 701:705 BMMCs 701:705 Real-time PCR showed the differential expressional profiles of 20 sialyltransferase (ST) genes in the both AML cell lines and bone marrow mononuclear cells (BMMCs) of AML patients. 24531716 5 8 theme marrow 675:680 arg1 cells 694:698 bone marrow mononuclear cells 670:698 bone marrow mononuclear cells (BMMCs) 670:706 Real-time PCR showed the differential expressional profiles of 20 sialyltransferase (ST) genes in the both AML cell lines and bone marrow mononuclear cells (BMMCs) of AML patients. 24531716 10 9 theme PI3K/Akt 1680:1687 arg1 signaling 1689:1697 PI3K/Akt signaling 1680:1697 PI3K/Akt signaling 1680:1697 Therefore, this study indicated that sialylation involved in the development of MDR of AML cells probably through ST3GAL5 or ST8SIA4 regulating the activity of PI3K/Akt signaling and the expression of P-gp and MRP1. 24531716 9 10 theme PI3K/Akt 1376:1383 arg1 pathway 1385:1391 the PI3K/Akt pathway 1372:1391 the PI3K/Akt pathway 1372:1391 Blocking the PI3K/Akt pathway by its specific inhibitor LY294002 or by Akt small interfering RNA resulted in the reduced chemosensitivity of HL60/ADR cells. 24531716 1 11 theme sialylation 123:133 arg1 patterns 135:142 Aberrant cell surface sialylation patterns 101:142 Aberrant cell surface sialylation patterns 101:142 Aberrant cell surface sialylation patterns have been shown to correlate with tumor progression and metastasis. 24531716 10 12 theme P-gp 1721:1724 arg1 activity 1668:1675 the activity 1664:1675 the activity of PI3K/Akt signaling 1664:1697 Therefore, this study indicated that sialylation involved in the development of MDR of AML cells probably through ST3GAL5 or ST8SIA4 regulating the activity of PI3K/Akt signaling and the expression of P-gp and MRP1. 24531716 10 12 theme P-gp 1721:1724 arg1 expression 1707:1716 the expression 1703:1716 the expression of P-gp and MRP1 1703:1733 Therefore, this study indicated that sialylation involved in the development of MDR of AML cells probably through ST3GAL5 or ST8SIA4 regulating the activity of PI3K/Akt signaling and the expression of P-gp and MRP1. 24531716 8 13 theme signaling 1159:1167 arg1 pathway 1169:1175 phosphoinositide-3 kinase (PI3K)/Akt signaling pathway 1122:1175 phosphoinositide-3 kinase (PI3K)/Akt signaling pathway 1122:1175 Further data demonstrated that manipulation of these two genes' expression modulated the activity of phosphoinositide-3 kinase (PI3K)/Akt signaling pathway and its downstream target thus regulated the proportionally mutative expression of P-glycoprotein (P-gp) and MDR-related protein 1 (MRP1), both of which are known to be involved in MDR. 24531716 8 14 theme mutative 1237:1244 arg1 expression 1246:1255 the proportionally mutative expression 1218:1255 the proportionally mutative expression of P-glycoprotein (P-gp) and MDR-related protein 1 (MRP1), both of which are known to be involved in MDR 1218:1360 Further data demonstrated that manipulation of these two genes' expression modulated the activity of phosphoinositide-3 kinase (PI3K)/Akt signaling pathway and its downstream target thus regulated the proportionally mutative expression of P-glycoprotein (P-gp) and MDR-related protein 1 (MRP1), both of which are known to be involved in MDR. 24531716 5 15 theme cell 655:658 arg1 lines 660:664 both AML cell lines 646:664 both AML cell lines 646:664 Real-time PCR showed the differential expressional profiles of 20 sialyltransferase (ST) genes in the both AML cell lines and bone marrow mononuclear cells (BMMCs) of AML patients. 24531716 9 16 theme specific 1400:1407 arg1 LY294002 1419:1426 its specific inhibitor LY294002 1396:1426 its specific inhibitor LY294002 1396:1426 Blocking the PI3K/Akt pathway by its specific inhibitor LY294002 or by Akt small interfering RNA resulted in the reduced chemosensitivity of HL60/ADR cells. 24531716 5 17 theme differential 569:580 arg1 profiles 595:602 the differential expressional profiles 565:602 the differential expressional profiles of 20 sialyltransferase (ST) genes in the both AML cell lines and bone marrow mononuclear cells (BMMCs) of AML patients 565:722 Real-time PCR showed the differential expressional profiles of 20 sialyltransferase (ST) genes in the both AML cell lines and bone marrow mononuclear cells (BMMCs) of AML patients. 24531716 5 18 theme Real-time 544:552 arg1 PCR 554:556 Real-time PCR 544:556 Real-time PCR 544:556 Real-time PCR showed the differential expressional profiles of 20 sialyltransferase (ST) genes in the both AML cell lines and bone marrow mononuclear cells (BMMCs) of AML patients. 24531716 2 19 theme cancer 259:264 arg1 MDR 288:290 MDR 288:290 MDR 288:290 However, the role of sialylation regulation of cancer multidrug resistance (MDR) remains poorly understood. 24531716 2 19 theme cancer 259:264 arg1 resistance 276:285 cancer multidrug resistance 259:285 cancer multidrug resistance (MDR) 259:291 However, the role of sialylation regulation of cancer multidrug resistance (MDR) remains poorly understood. 24531716 4 20 theme spectrometry 423:434 arg1 analysis 441:448 mass spectrometry (MS) analysis 418:448 mass spectrometry (MS) analysis 418:448 Using mass spectrometry (MS) analysis, the composition profiling of sialylated N-glycans differed in three pairs of AML cell lines. 24531716 5 21 theme patients 715:722 arg1 lines 660:664 both AML cell lines 646:664 both AML cell lines 646:664 Real-time PCR showed the differential expressional profiles of 20 sialyltransferase (ST) genes in the both AML cell lines and bone marrow mononuclear cells (BMMCs) of AML patients. 24531716 5 21 theme patients 715:722 arg1 BMMCs 701:705 BMMCs 701:705 BMMCs 701:705 Real-time PCR showed the differential expressional profiles of 20 sialyltransferase (ST) genes in the both AML cell lines and bone marrow mononuclear cells (BMMCs) of AML patients. 24531716 5 21 theme patients 715:722 arg1 cells 694:698 bone marrow mononuclear cells 670:698 bone marrow mononuclear cells (BMMCs) 670:706 Real-time PCR showed the differential expressional profiles of 20 sialyltransferase (ST) genes in the both AML cell lines and bone marrow mononuclear cells (BMMCs) of AML patients. 24531716 2 22 theme regulation 245:254 arg1 role 225:228 the role 221:228 the role of sialylation regulation of cancer multidrug resistance (MDR) 221:291 However, the role of sialylation regulation of cancer multidrug resistance (MDR) remains poorly understood. 24531716 4 23 theme sialylated 480:489 arg1 N-glycans 491:499 sialylated N-glycans 480:499 sialylated N-glycans 480:499 Using mass spectrometry (MS) analysis, the composition profiling of sialylated N-glycans differed in three pairs of AML cell lines. 24531716 7 24 theme HL60/ADR 979:986 arg1 cells 988:992 HL60 and HL60/ADR cells 970:992 HL60 and HL60/ADR cells both in vitro and in vivo 970:1018 The altered levels of ST3GAL5 and ST8SIA4 were found in close association with the MDR phenotype changing of HL60 and HL60/ADR cells both in vitro and in vivo. 24531716 0 25 theme acute 77:81 arg1 leukemia 91:98 human acute myeloid leukemia 71:98 human acute myeloid leukemia 71:98 Modification of sialylation is associated with multidrug resistance in human acute myeloid leukemia. 24531716 5 26 theme expressional 582:593 arg1 profiles 595:602 the differential expressional profiles 565:602 the differential expressional profiles of 20 sialyltransferase (ST) genes in the both AML cell lines and bone marrow mononuclear cells (BMMCs) of AML patients 565:722 Real-time PCR showed the differential expressional profiles of 20 sialyltransferase (ST) genes in the both AML cell lines and bone marrow mononuclear cells (BMMCs) of AML patients. 24531716 5 27 from profiles 595:602 arg1 lines 660:664 both AML cell lines 646:664 both AML cell lines 646:664 Real-time PCR showed the differential expressional profiles of 20 sialyltransferase (ST) genes in the both AML cell lines and bone marrow mononuclear cells (BMMCs) of AML patients. 24531716 5 27 from profiles 595:602 arg1 BMMCs 701:705 BMMCs 701:705 BMMCs 701:705 Real-time PCR showed the differential expressional profiles of 20 sialyltransferase (ST) genes in the both AML cell lines and bone marrow mononuclear cells (BMMCs) of AML patients. 24531716 5 27 from profiles 595:602 arg1 cells 694:698 bone marrow mononuclear cells 670:698 bone marrow mononuclear cells (BMMCs) 670:706 Real-time PCR showed the differential expressional profiles of 20 sialyltransferase (ST) genes in the both AML cell lines and bone marrow mononuclear cells (BMMCs) of AML patients. 24531716 5 28 dep lines 660:664 arg1 the 642:644 the 642:644 the 642:644 Real-time PCR showed the differential expressional profiles of 20 sialyltransferase (ST) genes in the both AML cell lines and bone marrow mononuclear cells (BMMCs) of AML patients. 24531716 8 29 theme MDR-related 1286:1296 arg1 protein 1298:1304 MDR-related protein 1 1286:1306 MDR-related protein 1 (MRP1) 1286:1313 Further data demonstrated that manipulation of these two genes' expression modulated the activity of phosphoinositide-3 kinase (PI3K)/Akt signaling pathway and its downstream target thus regulated the proportionally mutative expression of P-glycoprotein (P-gp) and MDR-related protein 1 (MRP1), both of which are known to be involved in MDR. 24531716 8 29 theme MDR-related 1286:1296 arg1 MRP1 1309:1312 MRP1 1309:1312 MRP1 1309:1312 Further data demonstrated that manipulation of these two genes' expression modulated the activity of phosphoinositide-3 kinase (PI3K)/Akt signaling pathway and its downstream target thus regulated the proportionally mutative expression of P-glycoprotein (P-gp) and MDR-related protein 1 (MRP1), both of which are known to be involved in MDR. 24531716 8 30 gly P-glycoprotein 1260:1273 arg1 P-gp 1276:1279 P-gp 1276:1279 P-gp 1276:1279 Further data demonstrated that manipulation of these two genes' expression modulated the activity of phosphoinositide-3 kinase (PI3K)/Akt signaling pathway and its downstream target thus regulated the proportionally mutative expression of P-glycoprotein (P-gp) and MDR-related protein 1 (MRP1), both of which are known to be involved in MDR. 24531716 8 30 gly P-glycoprotein 1260:1273 arg1 P-glycoprotein 1260:1273 P-glycoprotein 1260:1273 P-glycoprotein (P-gp) 1260:1280 Further data demonstrated that manipulation of these two genes' expression modulated the activity of phosphoinositide-3 kinase (PI3K)/Akt signaling pathway and its downstream target thus regulated the proportionally mutative expression of P-glycoprotein (P-gp) and MDR-related protein 1 (MRP1), both of which are known to be involved in MDR. 24531716 3 31 theme myeloid 388:394 arg1 AML 406:408 AML 406:408 AML 406:408 This study investigated sialylation in modification on MDR in acute myeloid leukemia (AML). 24531716 3 31 theme myeloid 388:394 arg1 leukemia 396:403 acute myeloid leukemia 382:403 acute myeloid leukemia (AML) 382:409 This study investigated sialylation in modification on MDR in acute myeloid leukemia (AML). 24531716 0 32 theme human 71:75 arg1 leukemia 91:98 human acute myeloid leukemia 71:98 human acute myeloid leukemia 71:98 Modification of sialylation is associated with multidrug resistance in human acute myeloid leukemia. 24531716 9 33 theme reduced 1476:1482 arg1 chemosensitivity 1484:1499 the reduced chemosensitivity 1472:1499 the reduced chemosensitivity of HL60/ADR cells 1472:1517 Blocking the PI3K/Akt pathway by its specific inhibitor LY294002 or by Akt small interfering RNA resulted in the reduced chemosensitivity of HL60/ADR cells. 24531716 4 34 theme cell 532:535 arg1 lines 537:541 AML cell lines 528:541 AML cell lines 528:541 Using mass spectrometry (MS) analysis, the composition profiling of sialylated N-glycans differed in three pairs of AML cell lines. 24531716 10 35 theme MDR 1600:1602 arg1 development 1585:1595 the development 1581:1595 the development of MDR of AML cells 1581:1615 Therefore, this study indicated that sialylation involved in the development of MDR of AML cells probably through ST3GAL5 or ST8SIA4 regulating the activity of PI3K/Akt signaling and the expression of P-gp and MRP1. 24531716 0 36 theme sialylation 16:26 arg1 Modification 0:11 Modification 0:11 Modification of sialylation 0:26 Modification of sialylation is associated with multidrug resistance in human acute myeloid leukemia. 24531716 6 37 theme HL60/adriamycin-resistant 822:846 arg1 cells 854:858 HL60 and HL60/adriamycin-resistant (ADR) cells 813:858 HL60 and HL60/adriamycin-resistant (ADR) cells 813:858 The expression levels of ST3GAL5 and ST8SIA4 were detected, which were overexpressed in HL60 and HL60/adriamycin-resistant (ADR) cells. 24531716 1 38 theme cell 110:113 arg1 patterns 135:142 Aberrant cell surface sialylation patterns 101:142 Aberrant cell surface sialylation patterns 101:142 Aberrant cell surface sialylation patterns have been shown to correlate with tumor progression and metastasis. 24531716 8 39 theme Further 1021:1027 arg1 data 1029:1032 Further data 1021:1032 Further data 1021:1032 Further data demonstrated that manipulation of these two genes' expression modulated the activity of phosphoinositide-3 kinase (PI3K)/Akt signaling pathway and its downstream target thus regulated the proportionally mutative expression of P-glycoprotein (P-gp) and MDR-related protein 1 (MRP1), both of which are known to be involved in MDR. 24531716 6 40 theme HL60 813:816 arg1 cells 854:858 HL60 and HL60/adriamycin-resistant (ADR) cells 813:858 HL60 and HL60/adriamycin-resistant (ADR) cells 813:858 The expression levels of ST3GAL5 and ST8SIA4 were detected, which were overexpressed in HL60 and HL60/adriamycin-resistant (ADR) cells. 24531716 9 41 theme cells 1513:1517 arg1 chemosensitivity 1484:1499 the reduced chemosensitivity 1472:1499 the reduced chemosensitivity of HL60/ADR cells 1472:1517 Blocking the PI3K/Akt pathway by its specific inhibitor LY294002 or by Akt small interfering RNA resulted in the reduced chemosensitivity of HL60/ADR cells. 24531716 5 42 dep sialyltransferase 610:626 arg1 ST 629:630 ST 629:630 ST 629:630 Real-time PCR showed the differential expressional profiles of 20 sialyltransferase (ST) genes in the both AML cell lines and bone marrow mononuclear cells (BMMCs) of AML patients. 24531716 0 43 theme multidrug 47:55 arg1 resistance 57:66 multidrug resistance 47:66 multidrug resistance in human acute myeloid leukemia 47:98 Modification of sialylation is associated with multidrug resistance in human acute myeloid leukemia. 24531716 3 44 gly investigated 331:342 arg1 modification 359:370 modification 359:370 modification on MDR in acute myeloid leukemia (AML) 359:409 This study investigated sialylation in modification on MDR in acute myeloid leukemia (AML). 24531716 10 45 theme MRP1 1730:1733 arg1 activity 1668:1675 the activity 1664:1675 the activity of PI3K/Akt signaling 1664:1697 Therefore, this study indicated that sialylation involved in the development of MDR of AML cells probably through ST3GAL5 or ST8SIA4 regulating the activity of PI3K/Akt signaling and the expression of P-gp and MRP1. 24531716 10 45 theme MRP1 1730:1733 arg1 expression 1707:1716 the expression 1703:1716 the expression of P-gp and MRP1 1703:1733 Therefore, this study indicated that sialylation involved in the development of MDR of AML cells probably through ST3GAL5 or ST8SIA4 regulating the activity of PI3K/Akt signaling and the expression of P-gp and MRP1. 24531716 10 46 theme AML 1607:1609 arg1 cells 1611:1615 AML cells 1607:1615 AML cells 1607:1615 Therefore, this study indicated that sialylation involved in the development of MDR of AML cells probably through ST3GAL5 or ST8SIA4 regulating the activity of PI3K/Akt signaling and the expression of P-gp and MRP1. 24531716 5 47 theme genes 633:637 arg1 profiles 595:602 the differential expressional profiles 565:602 the differential expressional profiles of 20 sialyltransferase (ST) genes in the both AML cell lines and bone marrow mononuclear cells (BMMCs) of AML patients 565:722 Real-time PCR showed the differential expressional profiles of 20 sialyltransferase (ST) genes in the both AML cell lines and bone marrow mononuclear cells (BMMCs) of AML patients. 24531716 8 48 theme expression 1085:1094 arg1 manipulation 1052:1063 manipulation 1052:1063 manipulation of these two genes' expression 1052:1094 Further data demonstrated that manipulation of these two genes' expression modulated the activity of phosphoinositide-3 kinase (PI3K)/Akt signaling pathway and its downstream target thus regulated the proportionally mutative expression of P-glycoprotein (P-gp) and MDR-related protein 1 (MRP1), both of which are known to be involved in MDR. 24531716 5 49 theme sialyltransferase 610:626 arg1 genes 633:637 20 sialyltransferase (ST) genes 607:637 20 sialyltransferase (ST) genes 607:637 Real-time PCR showed the differential expressional profiles of 20 sialyltransferase (ST) genes in the both AML cell lines and bone marrow mononuclear cells (BMMCs) of AML patients. 24531716 6 50 theme ADR 849:851 arg1 cells 854:858 HL60 and HL60/adriamycin-resistant (ADR) cells 813:858 HL60 and HL60/adriamycin-resistant (ADR) cells 813:858 The expression levels of ST3GAL5 and ST8SIA4 were detected, which were overexpressed in HL60 and HL60/adriamycin-resistant (ADR) cells. 24531716 8 51 theme pathway 1169:1175 arg1 activity 1110:1117 the activity 1106:1117 the activity of phosphoinositide-3 kinase (PI3K)/Akt signaling pathway 1106:1175 Further data demonstrated that manipulation of these two genes' expression modulated the activity of phosphoinositide-3 kinase (PI3K)/Akt signaling pathway and its downstream target thus regulated the proportionally mutative expression of P-glycoprotein (P-gp) and MDR-related protein 1 (MRP1), both of which are known to be involved in MDR. 24531716 5 52 theme bone 670:673 arg1 BMMCs 701:705 BMMCs 701:705 BMMCs 701:705 Real-time PCR showed the differential expressional profiles of 20 sialyltransferase (ST) genes in the both AML cell lines and bone marrow mononuclear cells (BMMCs) of AML patients. 24531716 5 52 theme bone 670:673 arg1 cells 694:698 bone marrow mononuclear cells 670:698 bone marrow mononuclear cells (BMMCs) 670:706 Real-time PCR showed the differential expressional profiles of 20 sialyltransferase (ST) genes in the both AML cell lines and bone marrow mononuclear cells (BMMCs) of AML patients. 24531716 6 53 theme expression 729:738 arg1 levels 740:745 The expression levels 725:745 The expression levels of ST3GAL5 and ST8SIA4 725:768 The expression levels of ST3GAL5 and ST8SIA4 were detected, which were overexpressed in HL60 and HL60/adriamycin-resistant (ADR) cells. 24531716 10 54 theme signaling 1689:1697 arg1 activity 1668:1675 the activity 1664:1675 the activity of PI3K/Akt signaling 1664:1697 Therefore, this study indicated that sialylation involved in the development of MDR of AML cells probably through ST3GAL5 or ST8SIA4 regulating the activity of PI3K/Akt signaling and the expression of P-gp and MRP1. 24531716 10 54 theme signaling 1689:1697 arg1 expression 1707:1716 the expression 1703:1716 the expression of P-gp and MRP1 1703:1733 Therefore, this study indicated that sialylation involved in the development of MDR of AML cells probably through ST3GAL5 or ST8SIA4 regulating the activity of PI3K/Akt signaling and the expression of P-gp and MRP1. 24531716 8 55 theme kinase 1141:1146 arg1 pathway 1169:1175 phosphoinositide-3 kinase (PI3K)/Akt signaling pathway 1122:1175 phosphoinositide-3 kinase (PI3K)/Akt signaling pathway 1122:1175 Further data demonstrated that manipulation of these two genes' expression modulated the activity of phosphoinositide-3 kinase (PI3K)/Akt signaling pathway and its downstream target thus regulated the proportionally mutative expression of P-glycoprotein (P-gp) and MDR-related protein 1 (MRP1), both of which are known to be involved in MDR. 24531716 9 56 theme small 1438:1442 arg1 RNA 1456:1458 Akt small interfering RNA 1434:1458 Akt small interfering RNA 1434:1458 Blocking the PI3K/Akt pathway by its specific inhibitor LY294002 or by Akt small interfering RNA resulted in the reduced chemosensitivity of HL60/ADR cells. 24531716 5 57 theme mononuclear 682:692 arg1 BMMCs 701:705 BMMCs 701:705 BMMCs 701:705 Real-time PCR showed the differential expressional profiles of 20 sialyltransferase (ST) genes in the both AML cell lines and bone marrow mononuclear cells (BMMCs) of AML patients. 24531716 5 57 theme mononuclear 682:692 arg1 cells 694:698 bone marrow mononuclear cells 670:698 bone marrow mononuclear cells (BMMCs) 670:706 Real-time PCR showed the differential expressional profiles of 20 sialyltransferase (ST) genes in the both AML cell lines and bone marrow mononuclear cells (BMMCs) of AML patients. 24531716 3 58 from modification 359:370 arg1 MDR 375:377 MDR 375:377 MDR in acute myeloid leukemia (AML) 375:409 This study investigated sialylation in modification on MDR in acute myeloid leukemia (AML). 24531716 2 59 theme sialylation 233:243 arg1 regulation 245:254 sialylation regulation 233:254 sialylation regulation of cancer multidrug resistance (MDR) 233:291 However, the role of sialylation regulation of cancer multidrug resistance (MDR) remains poorly understood. 24531716 8 60 theme PI3K 1149:1152 arg1 pathway 1169:1175 phosphoinositide-3 kinase (PI3K)/Akt signaling pathway 1122:1175 phosphoinositide-3 kinase (PI3K)/Akt signaling pathway 1122:1175 Further data demonstrated that manipulation of these two genes' expression modulated the activity of phosphoinositide-3 kinase (PI3K)/Akt signaling pathway and its downstream target thus regulated the proportionally mutative expression of P-glycoprotein (P-gp) and MDR-related protein 1 (MRP1), both of which are known to be involved in MDR. 24531716 7 61 located found 908:912 arg2 levels 873:878 The altered levels 861:878 The altered levels of ST3GAL5 and ST8SIA4 861:901 The altered levels of ST3GAL5 and ST8SIA4 were found in close association with the MDR phenotype changing of HL60 and HL60/ADR cells both in vitro and in vivo. 24531716 7 61 located found 908:912 arg1 association 923:933 close association 917:933 close association with the MDR phenotype changing of HL60 and HL60/ADR cells both in vitro and in vivo 917:1018 The altered levels of ST3GAL5 and ST8SIA4 were found in close association with the MDR phenotype changing of HL60 and HL60/ADR cells both in vitro and in vivo. 24531716 5 62 theme AML 651:653 arg1 lines 660:664 both AML cell lines 646:664 both AML cell lines 646:664 Real-time PCR showed the differential expressional profiles of 20 sialyltransferase (ST) genes in the both AML cell lines and bone marrow mononuclear cells (BMMCs) of AML patients. 24531716 3 63 from MDR 375:377 arg1 AML 406:408 AML 406:408 AML 406:408 This study investigated sialylation in modification on MDR in acute myeloid leukemia (AML). 24531716 3 63 from MDR 375:377 arg1 leukemia 396:403 acute myeloid leukemia 382:403 acute myeloid leukemia (AML) 382:409 This study investigated sialylation in modification on MDR in acute myeloid leukemia (AML). 24531716 7 64 theme HL60 970:973 arg1 cells 988:992 HL60 and HL60/ADR cells 970:992 HL60 and HL60/ADR cells both in vitro and in vivo 970:1018 The altered levels of ST3GAL5 and ST8SIA4 were found in close association with the MDR phenotype changing of HL60 and HL60/ADR cells both in vitro and in vivo. 24531716 1 65 theme surface 115:121 arg1 patterns 135:142 Aberrant cell surface sialylation patterns 101:142 Aberrant cell surface sialylation patterns 101:142 Aberrant cell surface sialylation patterns have been shown to correlate with tumor progression and metastasis. 24531716 8 66 theme /Akt 1154:1157 arg1 pathway 1169:1175 phosphoinositide-3 kinase (PI3K)/Akt signaling pathway 1122:1175 phosphoinositide-3 kinase (PI3K)/Akt signaling pathway 1122:1175 Further data demonstrated that manipulation of these two genes' expression modulated the activity of phosphoinositide-3 kinase (PI3K)/Akt signaling pathway and its downstream target thus regulated the proportionally mutative expression of P-glycoprotein (P-gp) and MDR-related protein 1 (MRP1), both of which are known to be involved in MDR. 24531716 4 67 theme mass 418:421 arg1 spectrometry 423:434 mass spectrometry 418:434 mass spectrometry (MS) analysis 418:448 Using mass spectrometry (MS) analysis, the composition profiling of sialylated N-glycans differed in three pairs of AML cell lines. 24531716 4 67 theme mass 418:421 arg1 MS 437:438 MS 437:438 MS 437:438 Using mass spectrometry (MS) analysis, the composition profiling of sialylated N-glycans differed in three pairs of AML cell lines. 24531716 2 68 theme multidrug 266:274 arg1 MDR 288:290 MDR 288:290 MDR 288:290 However, the role of sialylation regulation of cancer multidrug resistance (MDR) remains poorly understood. 24531716 2 68 theme multidrug 266:274 arg1 resistance 276:285 cancer multidrug resistance 259:285 cancer multidrug resistance (MDR) 259:291 However, the role of sialylation regulation of cancer multidrug resistance (MDR) remains poorly understood. 24531716 7 69 theme changing 958:965 arg1 phenotype 948:956 the MDR phenotype changing 940:965 the MDR phenotype changing of HL60 and HL60/ADR cells both in vitro and in vivo 940:1018 The altered levels of ST3GAL5 and ST8SIA4 were found in close association with the MDR phenotype changing of HL60 and HL60/ADR cells both in vitro and in vivo. 24531716 9 70 theme inhibitor 1409:1417 arg1 LY294002 1419:1426 its specific inhibitor LY294002 1396:1426 its specific inhibitor LY294002 1396:1426 Blocking the PI3K/Akt pathway by its specific inhibitor LY294002 or by Akt small interfering RNA resulted in the reduced chemosensitivity of HL60/ADR cells. 24531716 7 71 with association 923:933 arg1 phenotype 948:956 the MDR phenotype changing 940:965 the MDR phenotype changing of HL60 and HL60/ADR cells both in vitro and in vivo 940:1018 The altered levels of ST3GAL5 and ST8SIA4 were found in close association with the MDR phenotype changing of HL60 and HL60/ADR cells both in vitro and in vivo. 24531716 5 72 theme AML 711:713 arg1 patients 715:722 AML patients 711:722 AML patients 711:722 Real-time PCR showed the differential expressional profiles of 20 sialyltransferase (ST) genes in the both AML cell lines and bone marrow mononuclear cells (BMMCs) of AML patients. 24531716 7 73 theme MDR 944:946 arg1 phenotype 948:956 the MDR phenotype changing 940:965 the MDR phenotype changing of HL60 and HL60/ADR cells both in vitro and in vivo 940:1018 The altered levels of ST3GAL5 and ST8SIA4 were found in close association with the MDR phenotype changing of HL60 and HL60/ADR cells both in vitro and in vivo. 24531716 4 74 theme N-glycans 491:499 arg1 profiling 467:475 the composition profiling 451:475 the composition profiling of sialylated N-glycans 451:499 Using mass spectrometry (MS) analysis, the composition profiling of sialylated N-glycans differed in three pairs of AML cell lines. 24531716 8 75 theme P-glycoprotein 1260:1273 arg1 expression 1246:1255 the proportionally mutative expression 1218:1255 the proportionally mutative expression of P-glycoprotein (P-gp) and MDR-related protein 1 (MRP1), both of which are known to be involved in MDR 1218:1360 Further data demonstrated that manipulation of these two genes' expression modulated the activity of phosphoinositide-3 kinase (PI3K)/Akt signaling pathway and its downstream target thus regulated the proportionally mutative expression of P-glycoprotein (P-gp) and MDR-related protein 1 (MRP1), both of which are known to be involved in MDR. 24531716 0 76 theme myeloid 83:89 arg1 leukemia 91:98 human acute myeloid leukemia 71:98 human acute myeloid leukemia 71:98 Modification of sialylation is associated with multidrug resistance in human acute myeloid leukemia. 24531716 9 77 theme Akt 1434:1436 arg1 RNA 1456:1458 Akt small interfering RNA 1434:1458 Akt small interfering RNA 1434:1458 Blocking the PI3K/Akt pathway by its specific inhibitor LY294002 or by Akt small interfering RNA resulted in the reduced chemosensitivity of HL60/ADR cells. 24531716 0 78 from resistance 57:66 arg1 leukemia 91:98 human acute myeloid leukemia 71:98 human acute myeloid leukemia 71:98 Modification of sialylation is associated with multidrug resistance in human acute myeloid leukemia. 24531716 7 79 theme close 917:921 arg1 association 923:933 close association 917:933 close association with the MDR phenotype changing of HL60 and HL60/ADR cells both in vitro and in vivo 917:1018 The altered levels of ST3GAL5 and ST8SIA4 were found in close association with the MDR phenotype changing of HL60 and HL60/ADR cells both in vitro and in vivo. 24531716 9 80 theme interfering 1444:1454 arg1 RNA 1456:1458 Akt small interfering RNA 1434:1458 Akt small interfering RNA 1434:1458 Blocking the PI3K/Akt pathway by its specific inhibitor LY294002 or by Akt small interfering RNA resulted in the reduced chemosensitivity of HL60/ADR cells. 24531716 4 81 theme composition 455:465 arg1 profiling 467:475 the composition profiling 451:475 the composition profiling of sialylated N-glycans 451:499 Using mass spectrometry (MS) analysis, the composition profiling of sialylated N-glycans differed in three pairs of AML cell lines. 24531716 8 82 theme protein 1298:1304 arg1 expression 1246:1255 the proportionally mutative expression 1218:1255 the proportionally mutative expression of P-glycoprotein (P-gp) and MDR-related protein 1 (MRP1), both of which are known to be involved in MDR 1218:1360 Further data demonstrated that manipulation of these two genes' expression modulated the activity of phosphoinositide-3 kinase (PI3K)/Akt signaling pathway and its downstream target thus regulated the proportionally mutative expression of P-glycoprotein (P-gp) and MDR-related protein 1 (MRP1), both of which are known to be involved in MDR. 24531716 7 83 theme ST8SIA4 895:901 arg1 levels 873:878 The altered levels 861:878 The altered levels of ST3GAL5 and ST8SIA4 861:901 The altered levels of ST3GAL5 and ST8SIA4 were found in close association with the MDR phenotype changing of HL60 and HL60/ADR cells both in vitro and in vivo. 24531716 4 84 theme lines 537:541 arg1 pairs 519:523 three pairs 513:523 three pairs of AML cell lines 513:541 Using mass spectrometry (MS) analysis, the composition profiling of sialylated N-glycans differed in three pairs of AML cell lines. 24531716 7 85 theme ST3GAL5 883:889 arg1 levels 873:878 The altered levels 861:878 The altered levels of ST3GAL5 and ST8SIA4 861:901 The altered levels of ST3GAL5 and ST8SIA4 were found in close association with the MDR phenotype changing of HL60 and HL60/ADR cells both in vitro and in vivo. 24531716 1 86 theme Aberrant 101:108 arg1 patterns 135:142 Aberrant cell surface sialylation patterns 101:142 Aberrant cell surface sialylation patterns 101:142 Aberrant cell surface sialylation patterns have been shown to correlate with tumor progression and metastasis. 24531716 3 87 theme acute 382:386 arg1 AML 406:408 AML 406:408 AML 406:408 This study investigated sialylation in modification on MDR in acute myeloid leukemia (AML). 24531716 3 87 theme acute 382:386 arg1 leukemia 396:403 acute myeloid leukemia 382:403 acute myeloid leukemia (AML) 382:409 This study investigated sialylation in modification on MDR in acute myeloid leukemia (AML). 24531716 9 88 theme HL60/ADR 1504:1511 arg1 cells 1513:1517 HL60/ADR cells 1504:1517 HL60/ADR cells 1504:1517 Blocking the PI3K/Akt pathway by its specific inhibitor LY294002 or by Akt small interfering RNA resulted in the reduced chemosensitivity of HL60/ADR cells. 24531716 4 89 theme AML 528:530 arg1 lines 537:541 AML cell lines 528:541 AML cell lines 528:541 Using mass spectrometry (MS) analysis, the composition profiling of sialylated N-glycans differed in three pairs of AML cell lines. 24531716 10 90 theme cells 1611:1615 arg1 MDR 1600:1602 MDR 1600:1602 MDR of AML cells 1600:1615 Therefore, this study indicated that sialylation involved in the development of MDR of AML cells probably through ST3GAL5 or ST8SIA4 regulating the activity of PI3K/Akt signaling and the expression of P-gp and MRP1. 24531716 7 91 theme altered 865:871 arg1 levels 873:878 The altered levels 861:878 The altered levels of ST3GAL5 and ST8SIA4 861:901 The altered levels of ST3GAL5 and ST8SIA4 were found in close association with the MDR phenotype changing of HL60 and HL60/ADR cells both in vitro and in vivo. 29186656 10 0 link C-linked 1799:1806 arg1 adduct 1815:1820 the C-linked FBP-dG adduct 1795:1820 the C-linked FBP-dG adduct compared to the N-linked 4-aminobiphenyl-dG adduct (ABP-dG) 1795:1880 The greater propensity to generate the promutagenic syn conformation for the C-linked FBP-dG adduct compared to the N-linked 4-aminobiphenyl-dG adduct (ABP-dG) suggests greater mutagenicity for the C-linked analogue. 29186656 10 1 theme FBP-dG 1808:1813 arg1 adduct 1815:1820 the C-linked FBP-dG adduct 1795:1820 the C-linked FBP-dG adduct compared to the N-linked 4-aminobiphenyl-dG adduct (ABP-dG) 1795:1880 The greater propensity to generate the promutagenic syn conformation for the C-linked FBP-dG adduct compared to the N-linked 4-aminobiphenyl-dG adduct (ABP-dG) suggests greater mutagenicity for the C-linked analogue. 29186656 12 2 theme SMI 2098:2100 arg1 duplex 2102:2107 the SMI duplex 2094:2107 the SMI duplex 2094:2107 The turn-on emission response of FBP-dG in the SMI duplex may be a powerful tool for monitoring SMI formation in the NarI sequence upon synthesis with DNA polymerases. 29186656 6 3 theme flanking 1231:1238 arg1 bases 1240:1244 the flanking bases 1227:1244 the flanking bases 1227:1244 FBP-dG displays a strong preference for adopting a syn conformation in the fully paired NarI duplex to produce an intercalated structure that exhibits stacking interactions between the C-linked biphenyl and the flanking bases. 29186656 10 4 theme 4-aminobiphenyl-dG 1847:1864 arg1 ABP-dG 1874:1879 ABP-dG 1874:1879 ABP-dG 1874:1879 The greater propensity to generate the promutagenic syn conformation for the C-linked FBP-dG adduct compared to the N-linked 4-aminobiphenyl-dG adduct (ABP-dG) suggests greater mutagenicity for the C-linked analogue. 29186656 10 4 theme 4-aminobiphenyl-dG 1847:1864 arg1 adduct 1866:1871 the N-linked 4-aminobiphenyl-dG adduct 1834:1871 the N-linked 4-aminobiphenyl-dG adduct (ABP-dG) 1834:1880 The greater propensity to generate the promutagenic syn conformation for the C-linked FBP-dG adduct compared to the N-linked 4-aminobiphenyl-dG adduct (ABP-dG) suggests greater mutagenicity for the C-linked analogue. 29186656 11 5 theme type 1996:1999 arg1 effect 1967:1972 the effect 1963:1972 the effect of the adduct linkage type on the conformational properties of adducted DNA 1963:2048 These results highlight the effect of the adduct linkage type on the conformational properties of adducted DNA. 29186656 6 6 from conformation 1075:1086 arg1 duplex 1113:1118 the fully paired NarI duplex 1091:1118 the fully paired NarI duplex 1091:1118 FBP-dG displays a strong preference for adopting a syn conformation in the fully paired NarI duplex to produce an intercalated structure that exhibits stacking interactions between the C-linked biphenyl and the flanking bases. 29186656 3 7 theme ring 544:547 arg1 attachment 549:558 direct aryl ring attachment 532:558 direct aryl ring attachment to the dG moiety 532:575 Other carcinogenic species result in direct aryl ring attachment to the dG moiety, resulting in C-linked adducts. 29186656 6 8 theme C-linked 1205:1212 arg1 biphenyl 1214:1221 the C-linked biphenyl 1201:1221 the C-linked biphenyl 1201:1221 FBP-dG displays a strong preference for adopting a syn conformation in the fully paired NarI duplex to produce an intercalated structure that exhibits stacking interactions between the C-linked biphenyl and the flanking bases. 29186656 10 9 link N-linked 1838:1845 arg1 ABP-dG 1874:1879 ABP-dG 1874:1879 ABP-dG 1874:1879 The greater propensity to generate the promutagenic syn conformation for the C-linked FBP-dG adduct compared to the N-linked 4-aminobiphenyl-dG adduct (ABP-dG) suggests greater mutagenicity for the C-linked analogue. 29186656 10 9 link N-linked 1838:1845 arg1 adduct 1866:1871 the N-linked 4-aminobiphenyl-dG adduct 1834:1871 the N-linked 4-aminobiphenyl-dG adduct (ABP-dG) 1834:1880 The greater propensity to generate the promutagenic syn conformation for the C-linked FBP-dG adduct compared to the N-linked 4-aminobiphenyl-dG adduct (ABP-dG) suggests greater mutagenicity for the C-linked analogue. 29186656 10 10 theme greater 1891:1897 arg1 mutagenicity 1899:1910 greater mutagenicity 1891:1910 greater mutagenicity for the C-linked analogue 1891:1936 The greater propensity to generate the promutagenic syn conformation for the C-linked FBP-dG adduct compared to the N-linked 4-aminobiphenyl-dG adduct (ABP-dG) suggests greater mutagenicity for the C-linked analogue. 29186656 4 11 link N-linked 710:717 arg1 adducts 725:731 the corresponding N-linked C8-dG adducts 692:731 the corresponding N-linked C8-dG adducts 692:731 The resulting C-linked adducts have reduced conformational flexibility compared to the corresponding N-linked C8-dG adducts, which can alter their orientation in the DNA duplex. 29186656 7 12 contain containing 1344:1353 arg1 duplex 1337:1342 the slippage mutagenic intermediate (SMI) duplex 1295:1342 the slippage mutagenic intermediate (SMI) duplex containing the lesion and 5'-flanking base within a 2-base bulge 1295:1407 FBP-dG is also shown to significantly stabilize the slippage mutagenic intermediate (SMI) duplex containing the lesion and 5'-flanking base within a 2-base bulge. 29186656 7 12 contain containing 1344:1353 arg2 base 1382:1385 5'-flanking base 1370:1385 5'-flanking base 1370:1385 FBP-dG is also shown to significantly stabilize the slippage mutagenic intermediate (SMI) duplex containing the lesion and 5'-flanking base within a 2-base bulge. 29186656 7 12 contain containing 1344:1353 arg2 lesion 1359:1364 the lesion 1355:1364 the lesion 1355:1364 FBP-dG is also shown to significantly stabilize the slippage mutagenic intermediate (SMI) duplex containing the lesion and 5'-flanking base within a 2-base bulge. 29186656 3 13 theme dG 567:568 arg1 moiety 570:575 the dG moiety 563:575 the dG moiety 563:575 Other carcinogenic species result in direct aryl ring attachment to the dG moiety, resulting in C-linked adducts. 29186656 4 14 theme conformational 653:666 arg1 flexibility 668:678 reduced conformational flexibility 645:678 reduced conformational flexibility 645:678 The resulting C-linked adducts have reduced conformational flexibility compared to the corresponding N-linked C8-dG adducts, which can alter their orientation in the DNA duplex. 29186656 0 15 theme Enhanced 138:145 arg1 Formation 158:166 Enhanced Syn Adduct Formation 138:166 Enhanced Syn Adduct Formation 138:166 Conformational Preference and Fluorescence Response of a C-Linked C8-Biphenyl-Guanine Lesion in the NarI Mutational Hotspot: Evidence for Enhanced Syn Adduct Formation. 29186656 5 16 theme fluorescent 832:842 arg1 FBP-dG 874:879 FBP-dG 874:879 FBP-dG 874:879 Described herein are structural studies of a fluorescent C-linked 4-fluorobiphenyl-dG (FBP-dG) that has been incorporated into the reiterated G3-postion of the 12-mer NarI sequence and those containing other 5'-flanking nucleobases. 29186656 5 16 theme fluorescent 832:842 arg1 4-fluorobiphenyl-dG 853:871 a fluorescent C-linked 4-fluorobiphenyl-dG 830:871 a fluorescent C-linked 4-fluorobiphenyl-dG (FBP-dG) 830:880 Described herein are structural studies of a fluorescent C-linked 4-fluorobiphenyl-dG (FBP-dG) that has been incorporated into the reiterated G3-postion of the 12-mer NarI sequence and those containing other 5'-flanking nucleobases. 29186656 9 17 theme Molecular 1537:1545 arg1 dynamics 1547:1554 Molecular dynamics simulations and optical spectroscopy 1537:1591 Molecular dynamics simulations and optical spectroscopy for the NarI oligonucleotides containing the C-linked FBP-dG 1537:1652 Molecular dynamics simulations and optical spectroscopy for the NarI oligonucleotides containing the C-linked FBP-dG predict increased rigidity of the biphenyl in the syn conformation. 29186656 9 17 theme Molecular 1537:1545 arg1 simulations 1556:1566 simulations 1556:1566 simulations 1556:1566 Molecular dynamics simulations and optical spectroscopy for the NarI oligonucleotides containing the C-linked FBP-dG predict increased rigidity of the biphenyl in the syn conformation. 29186656 9 17 theme Molecular 1537:1545 arg1 spectroscopy 1580:1591 optical spectroscopy 1572:1591 optical spectroscopy 1572:1591 Molecular dynamics simulations and optical spectroscopy for the NarI oligonucleotides containing the C-linked FBP-dG predict increased rigidity of the biphenyl in the syn conformation. 29186656 12 18 theme emission 2063:2070 arg1 response 2072:2079 The turn-on emission response 2051:2079 The turn-on emission response of FBP-dG in the SMI duplex 2051:2107 The turn-on emission response of FBP-dG in the SMI duplex may be a powerful tool for monitoring SMI formation in the NarI sequence upon synthesis with DNA polymerases. 29186656 12 18 theme emission 2063:2070 arg1 tool 2127:2130 a powerful tool 2116:2130 a powerful tool for monitoring SMI formation in the NarI sequence upon synthesis with DNA polymerases 2116:2216 The turn-on emission response of FBP-dG in the SMI duplex may be a powerful tool for monitoring SMI formation in the NarI sequence upon synthesis with DNA polymerases. 29186656 10 19 theme C-linked 1799:1806 arg1 adduct 1815:1820 the C-linked FBP-dG adduct 1795:1820 the C-linked FBP-dG adduct compared to the N-linked 4-aminobiphenyl-dG adduct (ABP-dG) 1795:1880 The greater propensity to generate the promutagenic syn conformation for the C-linked FBP-dG adduct compared to the N-linked 4-aminobiphenyl-dG adduct (ABP-dG) suggests greater mutagenicity for the C-linked analogue. 29186656 0 20 theme Adduct 151:156 arg1 Formation 158:166 Enhanced Syn Adduct Formation 138:166 Enhanced Syn Adduct Formation 138:166 Conformational Preference and Fluorescence Response of a C-Linked C8-Biphenyl-Guanine Lesion in the NarI Mutational Hotspot: Evidence for Enhanced Syn Adduct Formation. 29186656 0 21 from Hotspot 116:122 arg1 Preference 15:24 Conformational Preference 0:24 Conformational Preference 0:24 Conformational Preference and Fluorescence Response of a C-Linked C8-Biphenyl-Guanine Lesion in the NarI Mutational Hotspot: Evidence for Enhanced Syn Adduct Formation. 29186656 0 21 from Hotspot 116:122 arg1 Response 43:50 Fluorescence Response 30:50 Fluorescence Response 30:50 Conformational Preference and Fluorescence Response of a C-Linked C8-Biphenyl-Guanine Lesion in the NarI Mutational Hotspot: Evidence for Enhanced Syn Adduct Formation. 29186656 8 22 theme paired 1522:1527 arg1 duplex 1529:1534 the fully paired duplex 1512:1534 the fully paired duplex 1512:1534 FBP-dG exhibits fluorescence sensitivity to SMI duplex formation that can readily distinguish it from the fully paired duplex. 29186656 9 23 theme increased 1662:1670 arg1 rigidity 1672:1679 increased rigidity 1662:1679 increased rigidity of the biphenyl in the syn conformation 1662:1719 Molecular dynamics simulations and optical spectroscopy for the NarI oligonucleotides containing the C-linked FBP-dG predict increased rigidity of the biphenyl in the syn conformation. 29186656 5 24 link C-linked 844:851 arg1 FBP-dG 874:879 FBP-dG 874:879 FBP-dG 874:879 Described herein are structural studies of a fluorescent C-linked 4-fluorobiphenyl-dG (FBP-dG) that has been incorporated into the reiterated G3-postion of the 12-mer NarI sequence and those containing other 5'-flanking nucleobases. 29186656 5 24 link C-linked 844:851 arg1 4-fluorobiphenyl-dG 853:871 a fluorescent C-linked 4-fluorobiphenyl-dG 830:871 a fluorescent C-linked 4-fluorobiphenyl-dG (FBP-dG) 830:880 Described herein are structural studies of a fluorescent C-linked 4-fluorobiphenyl-dG (FBP-dG) that has been incorporated into the reiterated G3-postion of the 12-mer NarI sequence and those containing other 5'-flanking nucleobases. 29186656 12 25 from formation 2151:2159 arg1 sequence 2173:2180 the NarI sequence 2164:2180 the NarI sequence 2164:2180 The turn-on emission response of FBP-dG in the SMI duplex may be a powerful tool for monitoring SMI formation in the NarI sequence upon synthesis with DNA polymerases. 29186656 5 26 theme NarI 954:957 arg1 sequence 959:966 the 12-mer NarI sequence 943:966 the 12-mer NarI sequence 943:966 Described herein are structural studies of a fluorescent C-linked 4-fluorobiphenyl-dG (FBP-dG) that has been incorporated into the reiterated G3-postion of the 12-mer NarI sequence and those containing other 5'-flanking nucleobases. 29186656 11 27 theme adducted 2037:2044 arg1 DNA 2046:2048 adducted DNA 2037:2048 adducted DNA 2037:2048 These results highlight the effect of the adduct linkage type on the conformational properties of adducted DNA. 29186656 4 28 theme N-linked 710:717 arg1 adducts 725:731 the corresponding N-linked C8-dG adducts 692:731 the corresponding N-linked C8-dG adducts 692:731 The resulting C-linked adducts have reduced conformational flexibility compared to the corresponding N-linked C8-dG adducts, which can alter their orientation in the DNA duplex. 29186656 0 29 theme C8-Biphenyl-Guanine 66:84 arg1 Lesion 86:91 a C-Linked C8-Biphenyl-Guanine Lesion 55:91 a C-Linked C8-Biphenyl-Guanine Lesion in the NarI Mutational Hotspot 55:122 Conformational Preference and Fluorescence Response of a C-Linked C8-Biphenyl-Guanine Lesion in the NarI Mutational Hotspot: Evidence for Enhanced Syn Adduct Formation. 29186656 1 30 attach attach 286:291 arg1 C8-site 311:317 the C8-site 307:317 the C8-site of 2'-deoxyguanosine (dG) 307:343 Aromatic chemical carcinogens can undergo enzymatic transformations to produce a range of electrophilic species that attach covalently to the C8-site of 2'-deoxyguanosine (dG) to afford C8-dG adducts. 29186656 1 30 attach attach 286:291 arg2 species 273:279 electrophilic species 259:279 electrophilic species that attach covalently to the C8-site of 2'-deoxyguanosine (dG) to afford C8-dG adducts 259:367 Aromatic chemical carcinogens can undergo enzymatic transformations to produce a range of electrophilic species that attach covalently to the C8-site of 2'-deoxyguanosine (dG) to afford C8-dG adducts. 29186656 1 30 attach attach 286:291 arg1 2'-deoxyguanosine 322:338 2'-deoxyguanosine 322:338 2'-deoxyguanosine 322:338 Aromatic chemical carcinogens can undergo enzymatic transformations to produce a range of electrophilic species that attach covalently to the C8-site of 2'-deoxyguanosine (dG) to afford C8-dG adducts. 29186656 1 31 theme C8-dG 355:359 arg1 adducts 361:367 C8-dG adducts 355:367 C8-dG adducts 355:367 Aromatic chemical carcinogens can undergo enzymatic transformations to produce a range of electrophilic species that attach covalently to the C8-site of 2'-deoxyguanosine (dG) to afford C8-dG adducts. 29186656 1 32 theme Aromatic 169:176 arg1 carcinogens 187:197 Aromatic chemical carcinogens 169:197 Aromatic chemical carcinogens 169:197 Aromatic chemical carcinogens can undergo enzymatic transformations to produce a range of electrophilic species that attach covalently to the C8-site of 2'-deoxyguanosine (dG) to afford C8-dG adducts. 29186656 6 33 link C-linked 1205:1212 arg1 biphenyl 1214:1221 the C-linked biphenyl 1201:1221 the C-linked biphenyl 1201:1221 FBP-dG displays a strong preference for adopting a syn conformation in the fully paired NarI duplex to produce an intercalated structure that exhibits stacking interactions between the C-linked biphenyl and the flanking bases. 29186656 0 34 theme NarI 100:103 arg1 Hotspot 116:122 the NarI Mutational Hotspot 96:122 the NarI Mutational Hotspot 96:122 Conformational Preference and Fluorescence Response of a C-Linked C8-Biphenyl-Guanine Lesion in the NarI Mutational Hotspot: Evidence for Enhanced Syn Adduct Formation. 29186656 5 35 theme 5'-flanking 995:1005 arg1 nucleobases 1007:1017 other 5'-flanking nucleobases 989:1017 other 5'-flanking nucleobases 989:1017 Described herein are structural studies of a fluorescent C-linked 4-fluorobiphenyl-dG (FBP-dG) that has been incorporated into the reiterated G3-postion of the 12-mer NarI sequence and those containing other 5'-flanking nucleobases. 29186656 9 36 from conformation 1708:1719 arg1 rigidity 1672:1679 increased rigidity 1662:1679 increased rigidity of the biphenyl in the syn conformation 1662:1719 Molecular dynamics simulations and optical spectroscopy for the NarI oligonucleotides containing the C-linked FBP-dG predict increased rigidity of the biphenyl in the syn conformation. 29186656 9 37 theme optical 1572:1578 arg1 dynamics 1547:1554 Molecular dynamics simulations and optical spectroscopy 1537:1591 Molecular dynamics simulations and optical spectroscopy for the NarI oligonucleotides containing the C-linked FBP-dG 1537:1652 Molecular dynamics simulations and optical spectroscopy for the NarI oligonucleotides containing the C-linked FBP-dG predict increased rigidity of the biphenyl in the syn conformation. 29186656 9 37 theme optical 1572:1578 arg1 spectroscopy 1580:1591 optical spectroscopy 1572:1591 optical spectroscopy 1572:1591 Molecular dynamics simulations and optical spectroscopy for the NarI oligonucleotides containing the C-linked FBP-dG predict increased rigidity of the biphenyl in the syn conformation. 29186656 10 38 theme promutagenic 1761:1772 arg1 conformation 1778:1789 the promutagenic syn conformation 1757:1789 the promutagenic syn conformation for the C-linked FBP-dG adduct compared to the N-linked 4-aminobiphenyl-dG adduct (ABP-dG) 1757:1880 The greater propensity to generate the promutagenic syn conformation for the C-linked FBP-dG adduct compared to the N-linked 4-aminobiphenyl-dG adduct (ABP-dG) suggests greater mutagenicity for the C-linked analogue. 29186656 9 39 dep dynamics 1547:1554 arg1 dynamics 1547:1554 Molecular dynamics simulations and optical spectroscopy 1537:1591 Molecular dynamics simulations and optical spectroscopy for the NarI oligonucleotides containing the C-linked FBP-dG 1537:1652 Molecular dynamics simulations and optical spectroscopy for the NarI oligonucleotides containing the C-linked FBP-dG predict increased rigidity of the biphenyl in the syn conformation. 29186656 9 39 dep dynamics 1547:1554 arg1 simulations 1556:1566 simulations 1556:1566 simulations 1556:1566 Molecular dynamics simulations and optical spectroscopy for the NarI oligonucleotides containing the C-linked FBP-dG predict increased rigidity of the biphenyl in the syn conformation. 29186656 9 39 dep dynamics 1547:1554 arg1 spectroscopy 1580:1591 optical spectroscopy 1572:1591 optical spectroscopy 1572:1591 Molecular dynamics simulations and optical spectroscopy for the NarI oligonucleotides containing the C-linked FBP-dG predict increased rigidity of the biphenyl in the syn conformation. 29186656 9 40 theme C-linked 1638:1645 arg1 FBP-dG 1647:1652 the C-linked FBP-dG 1634:1652 the C-linked FBP-dG 1634:1652 Molecular dynamics simulations and optical spectroscopy for the NarI oligonucleotides containing the C-linked FBP-dG predict increased rigidity of the biphenyl in the syn conformation. 29186656 6 41 theme NarI 1108:1111 arg1 duplex 1113:1118 the fully paired NarI duplex 1091:1118 the fully paired NarI duplex 1091:1118 FBP-dG displays a strong preference for adopting a syn conformation in the fully paired NarI duplex to produce an intercalated structure that exhibits stacking interactions between the C-linked biphenyl and the flanking bases. 29186656 0 42 from Response 43:50 arg1 Hotspot 116:122 the NarI Mutational Hotspot 96:122 the NarI Mutational Hotspot 96:122 Conformational Preference and Fluorescence Response of a C-Linked C8-Biphenyl-Guanine Lesion in the NarI Mutational Hotspot: Evidence for Enhanced Syn Adduct Formation. 29186656 10 43 theme greater 1726:1732 arg1 propensity 1734:1743 The greater propensity 1722:1743 The greater propensity to generate the promutagenic syn conformation for the C-linked FBP-dG adduct compared to the N-linked 4-aminobiphenyl-dG adduct (ABP-dG) 1722:1880 The greater propensity to generate the promutagenic syn conformation for the C-linked FBP-dG adduct compared to the N-linked 4-aminobiphenyl-dG adduct (ABP-dG) suggests greater mutagenicity for the C-linked analogue. 29186656 0 44 theme Conformational 0:13 arg1 Preference 15:24 Conformational Preference 0:24 Conformational Preference 0:24 Conformational Preference and Fluorescence Response of a C-Linked C8-Biphenyl-Guanine Lesion in the NarI Mutational Hotspot: Evidence for Enhanced Syn Adduct Formation. 29186656 4 45 from orientation 756:766 arg1 duplex 779:784 the DNA duplex 771:784 the DNA duplex 771:784 The resulting C-linked adducts have reduced conformational flexibility compared to the corresponding N-linked C8-dG adducts, which can alter their orientation in the DNA duplex. 29186656 9 46 from biphenyl 1688:1695 arg1 conformation 1708:1719 the syn conformation 1700:1719 the syn conformation 1700:1719 Molecular dynamics simulations and optical spectroscopy for the NarI oligonucleotides containing the C-linked FBP-dG predict increased rigidity of the biphenyl in the syn conformation. 29186656 7 47 theme 5'-flanking 1370:1380 arg1 base 1382:1385 5'-flanking base 1370:1385 5'-flanking base 1370:1385 FBP-dG is also shown to significantly stabilize the slippage mutagenic intermediate (SMI) duplex containing the lesion and 5'-flanking base within a 2-base bulge. 29186656 11 48 from effect 1967:1972 arg1 properties 2023:2032 the conformational properties 2004:2032 the conformational properties of adducted DNA 2004:2048 These results highlight the effect of the adduct linkage type on the conformational properties of adducted DNA. 29186656 10 49 theme syn 1774:1776 arg1 conformation 1778:1789 the promutagenic syn conformation 1757:1789 the promutagenic syn conformation for the C-linked FBP-dG adduct compared to the N-linked 4-aminobiphenyl-dG adduct (ABP-dG) 1757:1880 The greater propensity to generate the promutagenic syn conformation for the C-linked FBP-dG adduct compared to the N-linked 4-aminobiphenyl-dG adduct (ABP-dG) suggests greater mutagenicity for the C-linked analogue. 29186656 5 50 theme C-linked 844:851 arg1 FBP-dG 874:879 FBP-dG 874:879 FBP-dG 874:879 Described herein are structural studies of a fluorescent C-linked 4-fluorobiphenyl-dG (FBP-dG) that has been incorporated into the reiterated G3-postion of the 12-mer NarI sequence and those containing other 5'-flanking nucleobases. 29186656 5 50 theme C-linked 844:851 arg1 4-fluorobiphenyl-dG 853:871 a fluorescent C-linked 4-fluorobiphenyl-dG 830:871 a fluorescent C-linked 4-fluorobiphenyl-dG (FBP-dG) 830:880 Described herein are structural studies of a fluorescent C-linked 4-fluorobiphenyl-dG (FBP-dG) that has been incorporated into the reiterated G3-postion of the 12-mer NarI sequence and those containing other 5'-flanking nucleobases. 29186656 10 51 theme N-linked 1838:1845 arg1 ABP-dG 1874:1879 ABP-dG 1874:1879 ABP-dG 1874:1879 The greater propensity to generate the promutagenic syn conformation for the C-linked FBP-dG adduct compared to the N-linked 4-aminobiphenyl-dG adduct (ABP-dG) suggests greater mutagenicity for the C-linked analogue. 29186656 10 51 theme N-linked 1838:1845 arg1 adduct 1866:1871 the N-linked 4-aminobiphenyl-dG adduct 1834:1871 the N-linked 4-aminobiphenyl-dG adduct (ABP-dG) 1834:1880 The greater propensity to generate the promutagenic syn conformation for the C-linked FBP-dG adduct compared to the N-linked 4-aminobiphenyl-dG adduct (ABP-dG) suggests greater mutagenicity for the C-linked analogue. 29186656 4 52 link C-linked 623:630 arg1 adducts 632:638 The resulting C-linked adducts 609:638 The resulting C-linked adducts 609:638 The resulting C-linked adducts have reduced conformational flexibility compared to the corresponding N-linked C8-dG adducts, which can alter their orientation in the DNA duplex. 29186656 2 53 theme C8-aryl 479:485 arg1 moiety 487:492 the C8-aryl moiety 475:492 the C8-aryl moiety 475:492 The most studied C8-dG adducts are formed from arylamines and contain a N-linkage separating the dG from the C8-aryl moiety. 29186656 8 54 theme SMI 1454:1456 arg1 formation 1465:1473 SMI duplex formation 1454:1473 SMI duplex formation 1454:1473 FBP-dG exhibits fluorescence sensitivity to SMI duplex formation that can readily distinguish it from the fully paired duplex. 29186656 1 55 theme 2'-deoxyguanosine 322:338 arg1 C8-site 311:317 the C8-site 307:317 the C8-site of 2'-deoxyguanosine (dG) 307:343 Aromatic chemical carcinogens can undergo enzymatic transformations to produce a range of electrophilic species that attach covalently to the C8-site of 2'-deoxyguanosine (dG) to afford C8-dG adducts. 29186656 1 55 theme 2'-deoxyguanosine 322:338 arg1 2'-deoxyguanosine 322:338 2'-deoxyguanosine 322:338 2'-deoxyguanosine 322:338 Aromatic chemical carcinogens can undergo enzymatic transformations to produce a range of electrophilic species that attach covalently to the C8-site of 2'-deoxyguanosine (dG) to afford C8-dG adducts. 29186656 6 56 theme syn 1071:1073 arg1 conformation 1075:1086 a syn conformation 1069:1086 a syn conformation in the fully paired NarI duplex to produce an intercalated structure that exhibits stacking interactions between the C-linked biphenyl and the flanking bases 1069:1244 FBP-dG displays a strong preference for adopting a syn conformation in the fully paired NarI duplex to produce an intercalated structure that exhibits stacking interactions between the C-linked biphenyl and the flanking bases. 29186656 3 57 link C-linked 591:598 arg1 adducts 600:606 C-linked adducts 591:606 C-linked adducts 591:606 Other carcinogenic species result in direct aryl ring attachment to the dG moiety, resulting in C-linked adducts. 29186656 4 58 contain have 640:643 arg1 adducts 632:638 The resulting C-linked adducts 609:638 The resulting C-linked adducts 609:638 The resulting C-linked adducts have reduced conformational flexibility compared to the corresponding N-linked C8-dG adducts, which can alter their orientation in the DNA duplex. 29186656 4 58 contain have 640:643 arg2 flexibility 668:678 reduced conformational flexibility 645:678 reduced conformational flexibility 645:678 The resulting C-linked adducts have reduced conformational flexibility compared to the corresponding N-linked C8-dG adducts, which can alter their orientation in the DNA duplex. 29186656 3 59 theme Other 495:499 arg1 species 514:520 Other carcinogenic species 495:520 Other carcinogenic species 495:520 Other carcinogenic species result in direct aryl ring attachment to the dG moiety, resulting in C-linked adducts. 29186656 10 60 theme C-linked 1920:1927 arg1 analogue 1929:1936 the C-linked analogue 1916:1936 the C-linked analogue 1916:1936 The greater propensity to generate the promutagenic syn conformation for the C-linked FBP-dG adduct compared to the N-linked 4-aminobiphenyl-dG adduct (ABP-dG) suggests greater mutagenicity for the C-linked analogue. 29186656 9 61 theme syn 1704:1706 arg1 conformation 1708:1719 the syn conformation 1700:1719 the syn conformation 1700:1719 Molecular dynamics simulations and optical spectroscopy for the NarI oligonucleotides containing the C-linked FBP-dG predict increased rigidity of the biphenyl in the syn conformation. 29186656 2 62 theme studied 379:385 arg1 adducts 393:399 The most studied C8-dG adducts 370:399 The most studied C8-dG adducts 370:399 The most studied C8-dG adducts are formed from arylamines and contain a N-linkage separating the dG from the C8-aryl moiety. 29186656 0 63 theme C-Linked 57:64 arg1 Lesion 86:91 a C-Linked C8-Biphenyl-Guanine Lesion 55:91 a C-Linked C8-Biphenyl-Guanine Lesion in the NarI Mutational Hotspot 55:122 Conformational Preference and Fluorescence Response of a C-Linked C8-Biphenyl-Guanine Lesion in the NarI Mutational Hotspot: Evidence for Enhanced Syn Adduct Formation. 29186656 12 64 theme SMI 2147:2149 arg1 formation 2151:2159 SMI formation 2147:2159 SMI formation in the NarI sequence upon synthesis with DNA polymerases 2147:2216 The turn-on emission response of FBP-dG in the SMI duplex may be a powerful tool for monitoring SMI formation in the NarI sequence upon synthesis with DNA polymerases. 29186656 7 65 theme mutagenic 1308:1316 arg1 duplex 1337:1342 the slippage mutagenic intermediate (SMI) duplex 1295:1342 the slippage mutagenic intermediate (SMI) duplex containing the lesion and 5'-flanking base within a 2-base bulge 1295:1407 FBP-dG is also shown to significantly stabilize the slippage mutagenic intermediate (SMI) duplex containing the lesion and 5'-flanking base within a 2-base bulge. 29186656 4 66 theme resulting 613:621 arg1 adducts 632:638 The resulting C-linked adducts 609:638 The resulting C-linked adducts 609:638 The resulting C-linked adducts have reduced conformational flexibility compared to the corresponding N-linked C8-dG adducts, which can alter their orientation in the DNA duplex. 29186656 9 67 contain containing 1623:1632 arg1 oligonucleotides 1606:1621 the NarI oligonucleotides 1597:1621 the NarI oligonucleotides containing the C-linked FBP-dG 1597:1652 Molecular dynamics simulations and optical spectroscopy for the NarI oligonucleotides containing the C-linked FBP-dG predict increased rigidity of the biphenyl in the syn conformation. 29186656 9 67 contain containing 1623:1632 arg2 FBP-dG 1647:1652 the C-linked FBP-dG 1634:1652 the C-linked FBP-dG 1634:1652 Molecular dynamics simulations and optical spectroscopy for the NarI oligonucleotides containing the C-linked FBP-dG predict increased rigidity of the biphenyl in the syn conformation. 29186656 1 68 theme species 273:279 arg1 range 250:254 a range 248:254 a range of electrophilic species that attach covalently to the C8-site of 2'-deoxyguanosine (dG) to afford C8-dG adducts 248:367 Aromatic chemical carcinogens can undergo enzymatic transformations to produce a range of electrophilic species that attach covalently to the C8-site of 2'-deoxyguanosine (dG) to afford C8-dG adducts. 29186656 12 69 theme powerful 2118:2125 arg1 response 2072:2079 The turn-on emission response 2051:2079 The turn-on emission response of FBP-dG in the SMI duplex 2051:2107 The turn-on emission response of FBP-dG in the SMI duplex may be a powerful tool for monitoring SMI formation in the NarI sequence upon synthesis with DNA polymerases. 29186656 12 69 theme powerful 2118:2125 arg1 tool 2127:2130 a powerful tool 2116:2130 a powerful tool for monitoring SMI formation in the NarI sequence upon synthesis with DNA polymerases 2116:2216 The turn-on emission response of FBP-dG in the SMI duplex may be a powerful tool for monitoring SMI formation in the NarI sequence upon synthesis with DNA polymerases. 29186656 9 70 link C-linked 1638:1645 arg1 FBP-dG 1647:1652 the C-linked FBP-dG 1634:1652 the C-linked FBP-dG 1634:1652 Molecular dynamics simulations and optical spectroscopy for the NarI oligonucleotides containing the C-linked FBP-dG predict increased rigidity of the biphenyl in the syn conformation. 29186656 7 71 theme SMI 1332:1334 arg1 duplex 1337:1342 the slippage mutagenic intermediate (SMI) duplex 1295:1342 the slippage mutagenic intermediate (SMI) duplex containing the lesion and 5'-flanking base within a 2-base bulge 1295:1407 FBP-dG is also shown to significantly stabilize the slippage mutagenic intermediate (SMI) duplex containing the lesion and 5'-flanking base within a 2-base bulge. 29186656 3 72 theme aryl 539:542 arg1 attachment 549:558 direct aryl ring attachment 532:558 direct aryl ring attachment to the dG moiety 532:575 Other carcinogenic species result in direct aryl ring attachment to the dG moiety, resulting in C-linked adducts. 29186656 1 73 theme chemical 178:185 arg1 carcinogens 187:197 Aromatic chemical carcinogens 169:197 Aromatic chemical carcinogens 169:197 Aromatic chemical carcinogens can undergo enzymatic transformations to produce a range of electrophilic species that attach covalently to the C8-site of 2'-deoxyguanosine (dG) to afford C8-dG adducts. 29186656 5 74 contain containing 978:987 arg1 those 972:976 those 972:976 those 972:976 Described herein are structural studies of a fluorescent C-linked 4-fluorobiphenyl-dG (FBP-dG) that has been incorporated into the reiterated G3-postion of the 12-mer NarI sequence and those containing other 5'-flanking nucleobases. 29186656 5 74 contain containing 978:987 arg2 nucleobases 1007:1017 other 5'-flanking nucleobases 989:1017 other 5'-flanking nucleobases 989:1017 Described herein are structural studies of a fluorescent C-linked 4-fluorobiphenyl-dG (FBP-dG) that has been incorporated into the reiterated G3-postion of the 12-mer NarI sequence and those containing other 5'-flanking nucleobases. 29186656 1 75 theme enzymatic 211:219 arg1 transformations 221:235 enzymatic transformations 211:235 enzymatic transformations 211:235 Aromatic chemical carcinogens can undergo enzymatic transformations to produce a range of electrophilic species that attach covalently to the C8-site of 2'-deoxyguanosine (dG) to afford C8-dG adducts. 29186656 12 76 theme FBP-dG 2084:2089 arg1 response 2072:2079 The turn-on emission response 2051:2079 The turn-on emission response of FBP-dG in the SMI duplex 2051:2107 The turn-on emission response of FBP-dG in the SMI duplex may be a powerful tool for monitoring SMI formation in the NarI sequence upon synthesis with DNA polymerases. 29186656 12 76 theme FBP-dG 2084:2089 arg1 tool 2127:2130 a powerful tool 2116:2130 a powerful tool for monitoring SMI formation in the NarI sequence upon synthesis with DNA polymerases 2116:2216 The turn-on emission response of FBP-dG in the SMI duplex may be a powerful tool for monitoring SMI formation in the NarI sequence upon synthesis with DNA polymerases. 29186656 9 77 theme NarI 1601:1604 arg1 oligonucleotides 1606:1621 the NarI oligonucleotides 1597:1621 the NarI oligonucleotides containing the C-linked FBP-dG 1597:1652 Molecular dynamics simulations and optical spectroscopy for the NarI oligonucleotides containing the C-linked FBP-dG predict increased rigidity of the biphenyl in the syn conformation. 29186656 0 78 theme Syn 147:149 arg1 Formation 158:166 Enhanced Syn Adduct Formation 138:166 Enhanced Syn Adduct Formation 138:166 Conformational Preference and Fluorescence Response of a C-Linked C8-Biphenyl-Guanine Lesion in the NarI Mutational Hotspot: Evidence for Enhanced Syn Adduct Formation. 29186656 3 79 theme C-linked 591:598 arg1 adducts 600:606 C-linked adducts 591:606 C-linked adducts 591:606 Other carcinogenic species result in direct aryl ring attachment to the dG moiety, resulting in C-linked adducts. 29186656 0 80 from Lesion 86:91 arg1 Hotspot 116:122 the NarI Mutational Hotspot 96:122 the NarI Mutational Hotspot 96:122 Conformational Preference and Fluorescence Response of a C-Linked C8-Biphenyl-Guanine Lesion in the NarI Mutational Hotspot: Evidence for Enhanced Syn Adduct Formation. 29186656 4 81 theme reduced 645:651 arg1 flexibility 668:678 reduced conformational flexibility 645:678 reduced conformational flexibility 645:678 The resulting C-linked adducts have reduced conformational flexibility compared to the corresponding N-linked C8-dG adducts, which can alter their orientation in the DNA duplex. 29186656 12 82 theme turn-on 2055:2061 arg1 response 2072:2079 The turn-on emission response 2051:2079 The turn-on emission response of FBP-dG in the SMI duplex 2051:2107 The turn-on emission response of FBP-dG in the SMI duplex may be a powerful tool for monitoring SMI formation in the NarI sequence upon synthesis with DNA polymerases. 29186656 12 82 theme turn-on 2055:2061 arg1 tool 2127:2130 a powerful tool 2116:2130 a powerful tool for monitoring SMI formation in the NarI sequence upon synthesis with DNA polymerases 2116:2216 The turn-on emission response of FBP-dG in the SMI duplex may be a powerful tool for monitoring SMI formation in the NarI sequence upon synthesis with DNA polymerases. 29186656 5 83 theme 12-mer 947:952 arg1 sequence 959:966 the 12-mer NarI sequence 943:966 the 12-mer NarI sequence 943:966 Described herein are structural studies of a fluorescent C-linked 4-fluorobiphenyl-dG (FBP-dG) that has been incorporated into the reiterated G3-postion of the 12-mer NarI sequence and those containing other 5'-flanking nucleobases. 29186656 9 84 from rigidity 1672:1679 arg1 conformation 1708:1719 the syn conformation 1700:1719 the syn conformation 1700:1719 Molecular dynamics simulations and optical spectroscopy for the NarI oligonucleotides containing the C-linked FBP-dG predict increased rigidity of the biphenyl in the syn conformation. 29186656 12 85 theme NarI 2168:2171 arg1 sequence 2173:2180 the NarI sequence 2164:2180 the NarI sequence 2164:2180 The turn-on emission response of FBP-dG in the SMI duplex may be a powerful tool for monitoring SMI formation in the NarI sequence upon synthesis with DNA polymerases. 29186656 0 86 theme Lesion 86:91 arg1 Preference 15:24 Conformational Preference 0:24 Conformational Preference 0:24 Conformational Preference and Fluorescence Response of a C-Linked C8-Biphenyl-Guanine Lesion in the NarI Mutational Hotspot: Evidence for Enhanced Syn Adduct Formation. 29186656 0 86 theme Lesion 86:91 arg1 Response 43:50 Fluorescence Response 30:50 Fluorescence Response 30:50 Conformational Preference and Fluorescence Response of a C-Linked C8-Biphenyl-Guanine Lesion in the NarI Mutational Hotspot: Evidence for Enhanced Syn Adduct Formation. 29186656 2 87 contain contain 432:438 arg1 adducts 393:399 The most studied C8-dG adducts 370:399 The most studied C8-dG adducts 370:399 The most studied C8-dG adducts are formed from arylamines and contain a N-linkage separating the dG from the C8-aryl moiety. 29186656 2 87 contain contain 432:438 arg2 N-linkage 442:450 a N-linkage 440:450 a N-linkage separating the dG from the C8-aryl moiety 440:492 The most studied C8-dG adducts are formed from arylamines and contain a N-linkage separating the dG from the C8-aryl moiety. 29186656 5 88 theme 4-fluorobiphenyl-dG 853:871 arg1 studies 819:825 structural studies 808:825 structural studies of a fluorescent C-linked 4-fluorobiphenyl-dG (FBP-dG) that has been incorporated into the reiterated G3-postion of the 12-mer NarI sequence and those containing other 5'-flanking nucleobases 808:1017 Described herein are structural studies of a fluorescent C-linked 4-fluorobiphenyl-dG (FBP-dG) that has been incorporated into the reiterated G3-postion of the 12-mer NarI sequence and those containing other 5'-flanking nucleobases. 29186656 11 89 theme DNA 2046:2048 arg1 properties 2023:2032 the conformational properties 2004:2032 the conformational properties of adducted DNA 2004:2048 These results highlight the effect of the adduct linkage type on the conformational properties of adducted DNA. 29186656 7 90 theme 2-base 1396:1401 arg1 bulge 1403:1407 a 2-base bulge 1394:1407 a 2-base bulge 1394:1407 FBP-dG is also shown to significantly stabilize the slippage mutagenic intermediate (SMI) duplex containing the lesion and 5'-flanking base within a 2-base bulge. 29186656 4 91 theme corresponding 696:708 arg1 adducts 725:731 the corresponding N-linked C8-dG adducts 692:731 the corresponding N-linked C8-dG adducts 692:731 The resulting C-linked adducts have reduced conformational flexibility compared to the corresponding N-linked C8-dG adducts, which can alter their orientation in the DNA duplex. 29186656 5 92 theme reiterated 918:927 arg1 G3-postion 929:938 the reiterated G3-postion 914:938 the reiterated G3-postion of the 12-mer NarI sequence and those containing other 5'-flanking nucleobases 914:1017 Described herein are structural studies of a fluorescent C-linked 4-fluorobiphenyl-dG (FBP-dG) that has been incorporated into the reiterated G3-postion of the 12-mer NarI sequence and those containing other 5'-flanking nucleobases. 29186656 6 93 theme strong 1038:1043 arg1 preference 1045:1054 a strong preference 1036:1054 a strong preference for adopting a syn conformation in the fully paired NarI duplex to produce an intercalated structure that exhibits stacking interactions between the C-linked biphenyl and the flanking bases 1036:1244 FBP-dG displays a strong preference for adopting a syn conformation in the fully paired NarI duplex to produce an intercalated structure that exhibits stacking interactions between the C-linked biphenyl and the flanking bases. 29186656 0 94 from Preference 15:24 arg1 Hotspot 116:122 the NarI Mutational Hotspot 96:122 the NarI Mutational Hotspot 96:122 Conformational Preference and Fluorescence Response of a C-Linked C8-Biphenyl-Guanine Lesion in the NarI Mutational Hotspot: Evidence for Enhanced Syn Adduct Formation. 29186656 4 95 theme C8-dG 719:723 arg1 adducts 725:731 the corresponding N-linked C8-dG adducts 692:731 the corresponding N-linked C8-dG adducts 692:731 The resulting C-linked adducts have reduced conformational flexibility compared to the corresponding N-linked C8-dG adducts, which can alter their orientation in the DNA duplex. 29186656 10 96 link C-linked 1920:1927 arg1 analogue 1929:1936 the C-linked analogue 1916:1936 the C-linked analogue 1916:1936 The greater propensity to generate the promutagenic syn conformation for the C-linked FBP-dG adduct compared to the N-linked 4-aminobiphenyl-dG adduct (ABP-dG) suggests greater mutagenicity for the C-linked analogue. 29186656 0 97 theme Mutational 105:114 arg1 Hotspot 116:122 the NarI Mutational Hotspot 96:122 the NarI Mutational Hotspot 96:122 Conformational Preference and Fluorescence Response of a C-Linked C8-Biphenyl-Guanine Lesion in the NarI Mutational Hotspot: Evidence for Enhanced Syn Adduct Formation. 29186656 5 98 theme other 989:993 arg1 nucleobases 1007:1017 other 5'-flanking nucleobases 989:1017 other 5'-flanking nucleobases 989:1017 Described herein are structural studies of a fluorescent C-linked 4-fluorobiphenyl-dG (FBP-dG) that has been incorporated into the reiterated G3-postion of the 12-mer NarI sequence and those containing other 5'-flanking nucleobases. 29186656 4 99 theme DNA 775:777 arg1 duplex 779:784 the DNA duplex 771:784 the DNA duplex 771:784 The resulting C-linked adducts have reduced conformational flexibility compared to the corresponding N-linked C8-dG adducts, which can alter their orientation in the DNA duplex. 29186656 11 100 theme conformational 2008:2021 arg1 properties 2023:2032 the conformational properties 2004:2032 the conformational properties of adducted DNA 2004:2048 These results highlight the effect of the adduct linkage type on the conformational properties of adducted DNA. 29186656 5 101 theme sequence 959:966 arg1 G3-postion 929:938 the reiterated G3-postion 914:938 the reiterated G3-postion of the 12-mer NarI sequence and those containing other 5'-flanking nucleobases 914:1017 Described herein are structural studies of a fluorescent C-linked 4-fluorobiphenyl-dG (FBP-dG) that has been incorporated into the reiterated G3-postion of the 12-mer NarI sequence and those containing other 5'-flanking nucleobases. 29186656 6 102 theme paired 1101:1106 arg1 duplex 1113:1118 the fully paired NarI duplex 1091:1118 the fully paired NarI duplex 1091:1118 FBP-dG displays a strong preference for adopting a syn conformation in the fully paired NarI duplex to produce an intercalated structure that exhibits stacking interactions between the C-linked biphenyl and the flanking bases. 29186656 11 103 theme adduct 1981:1986 arg1 type 1996:1999 the adduct linkage type 1977:1999 the adduct linkage type 1977:1999 These results highlight the effect of the adduct linkage type on the conformational properties of adducted DNA. 29186656 2 104 theme C8-dG 387:391 arg1 adducts 393:399 The most studied C8-dG adducts 370:399 The most studied C8-dG adducts 370:399 The most studied C8-dG adducts are formed from arylamines and contain a N-linkage separating the dG from the C8-aryl moiety. 29186656 0 105 theme Fluorescence 30:41 arg1 Response 43:50 Fluorescence Response 30:50 Fluorescence Response 30:50 Conformational Preference and Fluorescence Response of a C-Linked C8-Biphenyl-Guanine Lesion in the NarI Mutational Hotspot: Evidence for Enhanced Syn Adduct Formation. 29186656 5 106 theme those 972:976 arg1 G3-postion 929:938 the reiterated G3-postion 914:938 the reiterated G3-postion of the 12-mer NarI sequence and those containing other 5'-flanking nucleobases 914:1017 Described herein are structural studies of a fluorescent C-linked 4-fluorobiphenyl-dG (FBP-dG) that has been incorporated into the reiterated G3-postion of the 12-mer NarI sequence and those containing other 5'-flanking nucleobases. 29186656 8 107 theme fluorescence 1426:1437 arg1 sensitivity 1439:1449 fluorescence sensitivity 1426:1449 fluorescence sensitivity to SMI duplex formation that can readily distinguish it from the fully paired duplex 1426:1534 FBP-dG exhibits fluorescence sensitivity to SMI duplex formation that can readily distinguish it from the fully paired duplex. 29186656 6 108 theme intercalated 1134:1145 arg1 structure 1147:1155 an intercalated structure 1131:1155 an intercalated structure that exhibits stacking interactions between the C-linked biphenyl and the flanking bases 1131:1244 FBP-dG displays a strong preference for adopting a syn conformation in the fully paired NarI duplex to produce an intercalated structure that exhibits stacking interactions between the C-linked biphenyl and the flanking bases. 29186656 12 109 theme DNA 2202:2204 arg1 polymerases 2206:2216 DNA polymerases 2202:2216 DNA polymerases 2202:2216 The turn-on emission response of FBP-dG in the SMI duplex may be a powerful tool for monitoring SMI formation in the NarI sequence upon synthesis with DNA polymerases. 29186656 5 110 theme structural 808:817 arg1 studies 819:825 structural studies 808:825 structural studies of a fluorescent C-linked 4-fluorobiphenyl-dG (FBP-dG) that has been incorporated into the reiterated G3-postion of the 12-mer NarI sequence and those containing other 5'-flanking nucleobases 808:1017 Described herein are structural studies of a fluorescent C-linked 4-fluorobiphenyl-dG (FBP-dG) that has been incorporated into the reiterated G3-postion of the 12-mer NarI sequence and those containing other 5'-flanking nucleobases. 29186656 12 111 from response 2072:2079 arg1 duplex 2102:2107 the SMI duplex 2094:2107 the SMI duplex 2094:2107 The turn-on emission response of FBP-dG in the SMI duplex may be a powerful tool for monitoring SMI formation in the NarI sequence upon synthesis with DNA polymerases. 29186656 9 112 theme biphenyl 1688:1695 arg1 rigidity 1672:1679 increased rigidity 1662:1679 increased rigidity of the biphenyl in the syn conformation 1662:1719 Molecular dynamics simulations and optical spectroscopy for the NarI oligonucleotides containing the C-linked FBP-dG predict increased rigidity of the biphenyl in the syn conformation. 29186656 6 113 theme stacking 1171:1178 arg1 interactions 1180:1191 stacking interactions 1171:1191 stacking interactions between the C-linked biphenyl and the flanking bases 1171:1244 FBP-dG displays a strong preference for adopting a syn conformation in the fully paired NarI duplex to produce an intercalated structure that exhibits stacking interactions between the C-linked biphenyl and the flanking bases. 29186656 8 114 theme duplex 1458:1463 arg1 formation 1465:1473 SMI duplex formation 1454:1473 SMI duplex formation 1454:1473 FBP-dG exhibits fluorescence sensitivity to SMI duplex formation that can readily distinguish it from the fully paired duplex. 29186656 3 115 theme carcinogenic 501:512 arg1 species 514:520 Other carcinogenic species 495:520 Other carcinogenic species 495:520 Other carcinogenic species result in direct aryl ring attachment to the dG moiety, resulting in C-linked adducts. 29186656 7 116 theme intermediate 1318:1329 arg1 duplex 1337:1342 the slippage mutagenic intermediate (SMI) duplex 1295:1342 the slippage mutagenic intermediate (SMI) duplex containing the lesion and 5'-flanking base within a 2-base bulge 1295:1407 FBP-dG is also shown to significantly stabilize the slippage mutagenic intermediate (SMI) duplex containing the lesion and 5'-flanking base within a 2-base bulge. 29186656 11 117 theme linkage 1988:1994 arg1 type 1996:1999 the adduct linkage type 1977:1999 the adduct linkage type 1977:1999 These results highlight the effect of the adduct linkage type on the conformational properties of adducted DNA. 29186656 0 118 dep Preference 15:24 arg1 Evidence 125:132 Evidence 125:132 Conformational Preference and Fluorescence Response of a C-Linked C8-Biphenyl-Guanine Lesion in the NarI Mutational Hotspot: Evidence for Enhanced Syn Adduct Formation. 0:167 Conformational Preference and Fluorescence Response of a C-Linked C8-Biphenyl-Guanine Lesion in the NarI Mutational Hotspot: Evidence for Enhanced Syn Adduct Formation. 29186656 7 119 theme slippage 1299:1306 arg1 duplex 1337:1342 the slippage mutagenic intermediate (SMI) duplex 1295:1342 the slippage mutagenic intermediate (SMI) duplex containing the lesion and 5'-flanking base within a 2-base bulge 1295:1407 FBP-dG is also shown to significantly stabilize the slippage mutagenic intermediate (SMI) duplex containing the lesion and 5'-flanking base within a 2-base bulge. 29186656 4 120 theme C-linked 623:630 arg1 adducts 632:638 The resulting C-linked adducts 609:638 The resulting C-linked adducts 609:638 The resulting C-linked adducts have reduced conformational flexibility compared to the corresponding N-linked C8-dG adducts, which can alter their orientation in the DNA duplex. 29186656 10 121 dep propensity 1734:1743 arg1 generate 1748:1755 generate 1748:1755 to generate the promutagenic syn conformation for the C-linked FBP-dG adduct compared to the N-linked 4-aminobiphenyl-dG adduct (ABP-dG) 1745:1880 The greater propensity to generate the promutagenic syn conformation for the C-linked FBP-dG adduct compared to the N-linked 4-aminobiphenyl-dG adduct (ABP-dG) suggests greater mutagenicity for the C-linked analogue. 29186656 12 122 with synthesis 2187:2195 arg1 polymerases 2206:2216 DNA polymerases 2202:2216 DNA polymerases 2202:2216 The turn-on emission response of FBP-dG in the SMI duplex may be a powerful tool for monitoring SMI formation in the NarI sequence upon synthesis with DNA polymerases. 29186656 3 123 theme direct 532:537 arg1 attachment 549:558 direct aryl ring attachment 532:558 direct aryl ring attachment to the dG moiety 532:575 Other carcinogenic species result in direct aryl ring attachment to the dG moiety, resulting in C-linked adducts. 29186656 1 124 theme electrophilic 259:271 arg1 species 273:279 electrophilic species 259:279 electrophilic species that attach covalently to the C8-site of 2'-deoxyguanosine (dG) to afford C8-dG adducts 259:367 Aromatic chemical carcinogens can undergo enzymatic transformations to produce a range of electrophilic species that attach covalently to the C8-site of 2'-deoxyguanosine (dG) to afford C8-dG adducts. 29016670 10 0 theme novel 1834:1838 arg1 function 1859:1866 the novel glycan-independent function 1830:1866 the novel glycan-independent function of serum glycoproteins in neuroprotective drug efficacy 1830:1922 Thus, two glycoproteins, AHSG and HPX, represent a pivotal glycoprotein of the cytoprotective activity for WN1316, showing a concrete evidence for the novel glycan-independent function of serum glycoproteins in neuroprotective drug efficacy. 29016670 10 1 gly glycoprotein 1742:1753 arg1 glycoprotein 1742:1753 a pivotal glycoprotein 1732:1753 a pivotal glycoprotein of the cytoprotective activity for WN1316 1732:1795 Thus, two glycoproteins, AHSG and HPX, represent a pivotal glycoprotein of the cytoprotective activity for WN1316, showing a concrete evidence for the novel glycan-independent function of serum glycoproteins in neuroprotective drug efficacy. 29016670 9 2 theme glycan 1597:1602 arg1 chains 1604:1609 glycan chains 1597:1609 glycan chains 1597:1609 Notably, the removal of glycan chains from these molecules did not affect the WN1316 cytoprotective activity. 29016670 4 3 theme novel 592:596 arg1 compound 613:620 the novel small-molecule compound 588:620 the novel small-molecule compound 588:620 We have previously reported the novel small-molecule compound, 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316), as a unique neuroprotectant against oxidative injury and a highly promising remedy for the treatment of amyotrophic lateral sclerosis (ALS). 29016670 4 3 theme novel 592:596 arg1 neuroprotectant 735:749 a unique neuroprotectant 726:749 a unique neuroprotectant against oxidative injury 726:774 We have previously reported the novel small-molecule compound, 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316), as a unique neuroprotectant against oxidative injury and a highly promising remedy for the treatment of amyotrophic lateral sclerosis (ALS). 29016670 4 3 theme novel 592:596 arg1 remedy 799:804 a highly promising remedy 780:804 a highly promising remedy for the treatment of amyotrophic lateral sclerosis (ALS) 780:861 We have previously reported the novel small-molecule compound, 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316), as a unique neuroprotectant against oxidative injury and a highly promising remedy for the treatment of amyotrophic lateral sclerosis (ALS). 29016670 4 3 theme novel 592:596 arg1 trihydrochloride 696:711 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316) 623:720 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316) 623:720 We have previously reported the novel small-molecule compound, 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316), as a unique neuroprotectant against oxidative injury and a highly promising remedy for the treatment of amyotrophic lateral sclerosis (ALS). 29016670 10 4 gly glycoproteins 1877:1889 arg1 glycoproteins 1877:1889 serum glycoproteins 1871:1889 serum glycoproteins in neuroprotective drug efficacy 1871:1922 Thus, two glycoproteins, AHSG and HPX, represent a pivotal glycoprotein of the cytoprotective activity for WN1316, showing a concrete evidence for the novel glycan-independent function of serum glycoproteins in neuroprotective drug efficacy. 29016670 4 5 theme amyotrophic 827:837 arg1 ALS 858:860 ALS 858:860 ALS 858:860 We have previously reported the novel small-molecule compound, 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316), as a unique neuroprotectant against oxidative injury and a highly promising remedy for the treatment of amyotrophic lateral sclerosis (ALS). 29016670 4 5 theme amyotrophic 827:837 arg1 sclerosis 847:855 amyotrophic lateral sclerosis 827:855 amyotrophic lateral sclerosis (ALS) 827:861 We have previously reported the novel small-molecule compound, 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316), as a unique neuroprotectant against oxidative injury and a highly promising remedy for the treatment of amyotrophic lateral sclerosis (ALS). 29016670 4 6 theme -N-[4- 647:652 arg1 compound 613:620 the novel small-molecule compound 588:620 the novel small-molecule compound 588:620 We have previously reported the novel small-molecule compound, 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316), as a unique neuroprotectant against oxidative injury and a highly promising remedy for the treatment of amyotrophic lateral sclerosis (ALS). 29016670 4 6 theme -N-[4- 647:652 arg1 trihydrochloride 696:711 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316) 623:720 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316) 623:720 We have previously reported the novel small-molecule compound, 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316), as a unique neuroprotectant against oxidative injury and a highly promising remedy for the treatment of amyotrophic lateral sclerosis (ALS). 29016670 10 7 theme serum 1871:1875 arg1 glycoproteins 1877:1889 serum glycoproteins 1871:1889 serum glycoproteins in neuroprotective drug efficacy 1871:1922 Thus, two glycoproteins, AHSG and HPX, represent a pivotal glycoprotein of the cytoprotective activity for WN1316, showing a concrete evidence for the novel glycan-independent function of serum glycoproteins in neuroprotective drug efficacy. 29016670 8 8 gly glycoproteins 1398:1410 arg1 hemopexin 1448:1456 hemopexin 1448:1456 hemopexin (HPX) 1448:1462 In this study, we sieved through fetal bovine serum proteins and identified two N-linked glycoproteins, alpha-2-HS-glycoprotein (AHSG) and hemopexin (HPX), requisites to exert the WN1316 cytoprotective activity against oxidative injury in neuronal cells in vitro. 29016670 8 8 gly glycoproteins 1398:1410 arg1 alpha-2-HS-glycoprotein 1413:1435 alpha-2-HS-glycoprotein 1413:1435 alpha-2-HS-glycoprotein (AHSG) 1413:1442 In this study, we sieved through fetal bovine serum proteins and identified two N-linked glycoproteins, alpha-2-HS-glycoprotein (AHSG) and hemopexin (HPX), requisites to exert the WN1316 cytoprotective activity against oxidative injury in neuronal cells in vitro. 29016670 8 8 gly glycoproteins 1398:1410 arg1 glycoproteins 1398:1410 two N-linked glycoproteins 1385:1410 two N-linked glycoproteins 1385:1410 In this study, we sieved through fetal bovine serum proteins and identified two N-linked glycoproteins, alpha-2-HS-glycoprotein (AHSG) and hemopexin (HPX), requisites to exert the WN1316 cytoprotective activity against oxidative injury in neuronal cells in vitro. 29016670 4 9 theme sclerosis 847:855 arg1 treatment 814:822 the treatment 810:822 the treatment of amyotrophic lateral sclerosis (ALS) 810:861 We have previously reported the novel small-molecule compound, 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316), as a unique neuroprotectant against oxidative injury and a highly promising remedy for the treatment of amyotrophic lateral sclerosis (ALS). 29016670 4 10 theme pyridin-2-yl 654:665 arg1 compound 613:620 the novel small-molecule compound 588:620 the novel small-molecule compound 588:620 We have previously reported the novel small-molecule compound, 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316), as a unique neuroprotectant against oxidative injury and a highly promising remedy for the treatment of amyotrophic lateral sclerosis (ALS). 29016670 4 10 theme pyridin-2-yl 654:665 arg1 trihydrochloride 696:711 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316) 623:720 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316) 623:720 We have previously reported the novel small-molecule compound, 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316), as a unique neuroprotectant against oxidative injury and a highly promising remedy for the treatment of amyotrophic lateral sclerosis (ALS). 29016670 8 11 gly alpha-2-HS-glycoprotein 1413:1435 arg1 AHSG 1438:1441 AHSG 1438:1441 AHSG 1438:1441 In this study, we sieved through fetal bovine serum proteins and identified two N-linked glycoproteins, alpha-2-HS-glycoprotein (AHSG) and hemopexin (HPX), requisites to exert the WN1316 cytoprotective activity against oxidative injury in neuronal cells in vitro. 29016670 8 11 gly alpha-2-HS-glycoprotein 1413:1435 arg1 alpha-2-HS-glycoprotein 1413:1435 alpha-2-HS-glycoprotein 1413:1435 alpha-2-HS-glycoprotein (AHSG) 1413:1442 In this study, we sieved through fetal bovine serum proteins and identified two N-linked glycoproteins, alpha-2-HS-glycoprotein (AHSG) and hemopexin (HPX), requisites to exert the WN1316 cytoprotective activity against oxidative injury in neuronal cells in vitro. 29016670 8 11 gly alpha-2-HS-glycoprotein 1413:1435 arg1 glycoproteins 1398:1410 two N-linked glycoproteins 1385:1410 two N-linked glycoproteins 1385:1410 In this study, we sieved through fetal bovine serum proteins and identified two N-linked glycoproteins, alpha-2-HS-glycoprotein (AHSG) and hemopexin (HPX), requisites to exert the WN1316 cytoprotective activity against oxidative injury in neuronal cells in vitro. 29016670 10 12 from function 1859:1866 arg1 efficacy 1915:1922 neuroprotective drug efficacy 1894:1922 neuroprotective drug efficacy 1894:1922 Thus, two glycoproteins, AHSG and HPX, represent a pivotal glycoprotein of the cytoprotective activity for WN1316, showing a concrete evidence for the novel glycan-independent function of serum glycoproteins in neuroprotective drug efficacy. 29016670 0 13 link N-linked 20:27 arg1 glycoproteins 29:41 N-linked glycoproteins 20:41 N-linked glycoproteins 20:41 A novel function of N-linked glycoproteins, alpha-2-HS-glycoprotein and hemopexin: Implications for small molecule compound-mediated neuroprotection. 29016670 0 13 link N-linked 20:27 arg1 hemopexin 72:80 hemopexin 72:80 hemopexin 72:80 A novel function of N-linked glycoproteins, alpha-2-HS-glycoprotein and hemopexin: Implications for small molecule compound-mediated neuroprotection. 29016670 0 13 link N-linked 20:27 arg1 alpha-2-HS-glycoprotein 44:66 alpha-2-HS-glycoprotein 44:66 alpha-2-HS-glycoprotein 44:66 A novel function of N-linked glycoproteins, alpha-2-HS-glycoprotein and hemopexin: Implications for small molecule compound-mediated neuroprotection. 29016670 6 14 theme cultured 1115:1122 arg1 cells 1124:1128 cultured cells 1115:1128 cultured cells 1115:1128 It is also noted that the WN1316 cytoprotective activity observed in cultured cells is totally dependent upon the addition of fetal bovine serum in culture medium. 29016670 4 15 theme methyl 634:639 arg1 compound 613:620 the novel small-molecule compound 588:620 the novel small-molecule compound 588:620 We have previously reported the novel small-molecule compound, 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316), as a unique neuroprotectant against oxidative injury and a highly promising remedy for the treatment of amyotrophic lateral sclerosis (ALS). 29016670 4 15 theme methyl 634:639 arg1 trihydrochloride 696:711 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316) 623:720 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316) 623:720 We have previously reported the novel small-molecule compound, 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316), as a unique neuroprotectant against oxidative injury and a highly promising remedy for the treatment of amyotrophic lateral sclerosis (ALS). 29016670 10 16 theme drug 1910:1913 arg1 efficacy 1915:1922 neuroprotective drug efficacy 1894:1922 neuroprotective drug efficacy 1894:1922 Thus, two glycoproteins, AHSG and HPX, represent a pivotal glycoprotein of the cytoprotective activity for WN1316, showing a concrete evidence for the novel glycan-independent function of serum glycoproteins in neuroprotective drug efficacy. 29016670 8 17 theme N-linked 1389:1396 arg1 hemopexin 1448:1456 hemopexin 1448:1456 hemopexin (HPX) 1448:1462 In this study, we sieved through fetal bovine serum proteins and identified two N-linked glycoproteins, alpha-2-HS-glycoprotein (AHSG) and hemopexin (HPX), requisites to exert the WN1316 cytoprotective activity against oxidative injury in neuronal cells in vitro. 29016670 8 17 theme N-linked 1389:1396 arg1 alpha-2-HS-glycoprotein 1413:1435 alpha-2-HS-glycoprotein 1413:1435 alpha-2-HS-glycoprotein (AHSG) 1413:1442 In this study, we sieved through fetal bovine serum proteins and identified two N-linked glycoproteins, alpha-2-HS-glycoprotein (AHSG) and hemopexin (HPX), requisites to exert the WN1316 cytoprotective activity against oxidative injury in neuronal cells in vitro. 29016670 8 17 theme N-linked 1389:1396 arg1 glycoproteins 1398:1410 two N-linked glycoproteins 1385:1410 two N-linked glycoproteins 1385:1410 In this study, we sieved through fetal bovine serum proteins and identified two N-linked glycoproteins, alpha-2-HS-glycoprotein (AHSG) and hemopexin (HPX), requisites to exert the WN1316 cytoprotective activity against oxidative injury in neuronal cells in vitro. 29016670 4 18 theme amino 641:645 arg1 compound 613:620 the novel small-molecule compound 588:620 the novel small-molecule compound 588:620 We have previously reported the novel small-molecule compound, 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316), as a unique neuroprotectant against oxidative injury and a highly promising remedy for the treatment of amyotrophic lateral sclerosis (ALS). 29016670 4 18 theme amino 641:645 arg1 trihydrochloride 696:711 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316) 623:720 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316) 623:720 We have previously reported the novel small-molecule compound, 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316), as a unique neuroprotectant against oxidative injury and a highly promising remedy for the treatment of amyotrophic lateral sclerosis (ALS). 29016670 10 19 theme pivotal 1734:1740 arg1 glycoprotein 1742:1753 a pivotal glycoprotein 1732:1753 a pivotal glycoprotein of the cytoprotective activity for WN1316 1732:1795 Thus, two glycoproteins, AHSG and HPX, represent a pivotal glycoprotein of the cytoprotective activity for WN1316, showing a concrete evidence for the novel glycan-independent function of serum glycoproteins in neuroprotective drug efficacy. 29016670 9 20 theme cytoprotective 1658:1671 arg1 activity 1673:1680 the WN1316 cytoprotective activity 1647:1680 the WN1316 cytoprotective activity 1647:1680 Notably, the removal of glycan chains from these molecules did not affect the WN1316 cytoprotective activity. 29016670 4 21 theme small-molecule 598:611 arg1 compound 613:620 the novel small-molecule compound 588:620 the novel small-molecule compound 588:620 We have previously reported the novel small-molecule compound, 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316), as a unique neuroprotectant against oxidative injury and a highly promising remedy for the treatment of amyotrophic lateral sclerosis (ALS). 29016670 4 21 theme small-molecule 598:611 arg1 neuroprotectant 735:749 a unique neuroprotectant 726:749 a unique neuroprotectant against oxidative injury 726:774 We have previously reported the novel small-molecule compound, 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316), as a unique neuroprotectant against oxidative injury and a highly promising remedy for the treatment of amyotrophic lateral sclerosis (ALS). 29016670 4 21 theme small-molecule 598:611 arg1 remedy 799:804 a highly promising remedy 780:804 a highly promising remedy for the treatment of amyotrophic lateral sclerosis (ALS) 780:861 We have previously reported the novel small-molecule compound, 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316), as a unique neuroprotectant against oxidative injury and a highly promising remedy for the treatment of amyotrophic lateral sclerosis (ALS). 29016670 4 21 theme small-molecule 598:611 arg1 trihydrochloride 696:711 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316) 623:720 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316) 623:720 We have previously reported the novel small-molecule compound, 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316), as a unique neuroprotectant against oxidative injury and a highly promising remedy for the treatment of amyotrophic lateral sclerosis (ALS). 29016670 6 22 located observed 1103:1110 arg1 cells 1124:1128 cultured cells 1115:1128 cultured cells 1115:1128 It is also noted that the WN1316 cytoprotective activity observed in cultured cells is totally dependent upon the addition of fetal bovine serum in culture medium. 29016670 6 22 located observed 1103:1110 arg2 dependent 1141:1149 dependent 1141:1149 dependent 1141:1149 It is also noted that the WN1316 cytoprotective activity observed in cultured cells is totally dependent upon the addition of fetal bovine serum in culture medium. 29016670 6 22 located observed 1103:1110 arg2 activity 1094:1101 the WN1316 cytoprotective activity 1068:1101 the WN1316 cytoprotective activity observed in cultured cells 1068:1128 It is also noted that the WN1316 cytoprotective activity observed in cultured cells is totally dependent upon the addition of fetal bovine serum in culture medium. 29016670 6 23 theme bovine 1178:1183 arg1 serum 1185:1189 fetal bovine serum 1172:1189 fetal bovine serum 1172:1189 It is also noted that the WN1316 cytoprotective activity observed in cultured cells is totally dependent upon the addition of fetal bovine serum in culture medium. 29016670 5 24 theme human 1024:1028 arg1 cells 1039:1043 cultured human neuronal cells 1015:1043 cultured human neuronal cells 1015:1043 One of the remarkable characteristics of WN1316 is that its efficacious doses in ALS mouse models are much less than those against oxidative injury in cultured human neuronal cells. 29016670 10 25 theme cytoprotective 1762:1775 arg1 activity 1777:1784 the cytoprotective activity 1758:1784 the cytoprotective activity for WN1316 1758:1795 Thus, two glycoproteins, AHSG and HPX, represent a pivotal glycoprotein of the cytoprotective activity for WN1316, showing a concrete evidence for the novel glycan-independent function of serum glycoproteins in neuroprotective drug efficacy. 29016670 5 26 theme WN1316 905:910 arg1 characteristics 886:900 the remarkable characteristics 871:900 the remarkable characteristics of WN1316 871:910 One of the remarkable characteristics of WN1316 is that its efficacious doses in ALS mouse models are much less than those against oxidative injury in cultured human neuronal cells. 29016670 4 27 theme -1H-imidazol-2-yl 667:683 arg1 compound 613:620 the novel small-molecule compound 588:620 the novel small-molecule compound 588:620 We have previously reported the novel small-molecule compound, 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316), as a unique neuroprotectant against oxidative injury and a highly promising remedy for the treatment of amyotrophic lateral sclerosis (ALS). 29016670 4 27 theme -1H-imidazol-2-yl 667:683 arg1 trihydrochloride 696:711 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316) 623:720 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316) 623:720 We have previously reported the novel small-molecule compound, 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316), as a unique neuroprotectant against oxidative injury and a highly promising remedy for the treatment of amyotrophic lateral sclerosis (ALS). 29016670 4 28 theme acetamide 686:694 arg1 compound 613:620 the novel small-molecule compound 588:620 the novel small-molecule compound 588:620 We have previously reported the novel small-molecule compound, 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316), as a unique neuroprotectant against oxidative injury and a highly promising remedy for the treatment of amyotrophic lateral sclerosis (ALS). 29016670 4 28 theme acetamide 686:694 arg1 trihydrochloride 696:711 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316) 623:720 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316) 623:720 We have previously reported the novel small-molecule compound, 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316), as a unique neuroprotectant against oxidative injury and a highly promising remedy for the treatment of amyotrophic lateral sclerosis (ALS). 29016670 6 29 from addition 1160:1167 arg1 medium 1202:1207 culture medium 1194:1207 culture medium 1194:1207 It is also noted that the WN1316 cytoprotective activity observed in cultured cells is totally dependent upon the addition of fetal bovine serum in culture medium. 29016670 1 30 theme nervous 184:190 arg1 CNS 200:202 CNS 200:202 CNS 200:202 Therapeutic agents to the central nervous system (CNS) need to be efficiently delivered to the target site of action at appropriate therapeutic levels. 29016670 1 30 theme nervous 184:190 arg1 system 192:197 the central nervous system 172:197 the central nervous system (CNS) 172:203 Therapeutic agents to the central nervous system (CNS) need to be efficiently delivered to the target site of action at appropriate therapeutic levels. 29016670 10 31 from efficacy 1915:1922 arg1 function 1859:1866 the novel glycan-independent function 1830:1866 the novel glycan-independent function of serum glycoproteins in neuroprotective drug efficacy 1830:1922 Thus, two glycoproteins, AHSG and HPX, represent a pivotal glycoprotein of the cytoprotective activity for WN1316, showing a concrete evidence for the novel glycan-independent function of serum glycoproteins in neuroprotective drug efficacy. 29016670 5 32 theme ALS 945:947 arg1 models 955:960 ALS mouse models 945:960 ALS mouse models 945:960 One of the remarkable characteristics of WN1316 is that its efficacious doses in ALS mouse models are much less than those against oxidative injury in cultured human neuronal cells. 29016670 0 33 theme molecule 106:113 arg1 neuroprotection 133:147 small molecule compound-mediated neuroprotection 100:147 small molecule compound-mediated neuroprotection 100:147 A novel function of N-linked glycoproteins, alpha-2-HS-glycoprotein and hemopexin: Implications for small molecule compound-mediated neuroprotection. 29016670 2 34 theme diseases 381:388 arg1 treatment 355:363 the treatment 351:363 the treatment of neurological diseases 351:388 However, a limited number of effective drugs for the treatment of neurological diseases has been developed thus far. 29016670 1 35 theme appropriate 270:280 arg1 levels 294:299 appropriate therapeutic levels 270:299 appropriate therapeutic levels 270:299 Therapeutic agents to the central nervous system (CNS) need to be efficiently delivered to the target site of action at appropriate therapeutic levels. 29016670 8 36 link N-linked 1389:1396 arg1 hemopexin 1448:1456 hemopexin 1448:1456 hemopexin (HPX) 1448:1462 In this study, we sieved through fetal bovine serum proteins and identified two N-linked glycoproteins, alpha-2-HS-glycoprotein (AHSG) and hemopexin (HPX), requisites to exert the WN1316 cytoprotective activity against oxidative injury in neuronal cells in vitro. 29016670 8 36 link N-linked 1389:1396 arg1 alpha-2-HS-glycoprotein 1413:1435 alpha-2-HS-glycoprotein 1413:1435 alpha-2-HS-glycoprotein (AHSG) 1413:1442 In this study, we sieved through fetal bovine serum proteins and identified two N-linked glycoproteins, alpha-2-HS-glycoprotein (AHSG) and hemopexin (HPX), requisites to exert the WN1316 cytoprotective activity against oxidative injury in neuronal cells in vitro. 29016670 8 36 link N-linked 1389:1396 arg1 glycoproteins 1398:1410 two N-linked glycoproteins 1385:1410 two N-linked glycoproteins 1385:1410 In this study, we sieved through fetal bovine serum proteins and identified two N-linked glycoproteins, alpha-2-HS-glycoprotein (AHSG) and hemopexin (HPX), requisites to exert the WN1316 cytoprotective activity against oxidative injury in neuronal cells in vitro. 29016670 4 37 theme unique 728:733 arg1 compound 613:620 the novel small-molecule compound 588:620 the novel small-molecule compound 588:620 We have previously reported the novel small-molecule compound, 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316), as a unique neuroprotectant against oxidative injury and a highly promising remedy for the treatment of amyotrophic lateral sclerosis (ALS). 29016670 4 37 theme unique 728:733 arg1 neuroprotectant 735:749 a unique neuroprotectant 726:749 a unique neuroprotectant against oxidative injury 726:774 We have previously reported the novel small-molecule compound, 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316), as a unique neuroprotectant against oxidative injury and a highly promising remedy for the treatment of amyotrophic lateral sclerosis (ALS). 29016670 8 38 theme cytoprotective 1496:1509 arg1 activity 1511:1518 the WN1316 cytoprotective activity 1485:1518 the WN1316 cytoprotective activity against oxidative injury in neuronal cells 1485:1561 In this study, we sieved through fetal bovine serum proteins and identified two N-linked glycoproteins, alpha-2-HS-glycoprotein (AHSG) and hemopexin (HPX), requisites to exert the WN1316 cytoprotective activity against oxidative injury in neuronal cells in vitro. 29016670 8 39 theme fetal 1342:1346 arg1 proteins 1361:1368 fetal bovine serum proteins 1342:1368 fetal bovine serum proteins 1342:1368 In this study, we sieved through fetal bovine serum proteins and identified two N-linked glycoproteins, alpha-2-HS-glycoprotein (AHSG) and hemopexin (HPX), requisites to exert the WN1316 cytoprotective activity against oxidative injury in neuronal cells in vitro. 29016670 0 40 theme N-linked 20:27 arg1 glycoproteins 29:41 N-linked glycoproteins 20:41 N-linked glycoproteins 20:41 A novel function of N-linked glycoproteins, alpha-2-HS-glycoprotein and hemopexin: Implications for small molecule compound-mediated neuroprotection. 29016670 0 40 theme N-linked 20:27 arg1 hemopexin 72:80 hemopexin 72:80 hemopexin 72:80 A novel function of N-linked glycoproteins, alpha-2-HS-glycoprotein and hemopexin: Implications for small molecule compound-mediated neuroprotection. 29016670 0 40 theme N-linked 20:27 arg1 alpha-2-HS-glycoprotein 44:66 alpha-2-HS-glycoprotein 44:66 alpha-2-HS-glycoprotein 44:66 A novel function of N-linked glycoproteins, alpha-2-HS-glycoprotein and hemopexin: Implications for small molecule compound-mediated neuroprotection. 29016670 10 41 gly glycoproteins 1693:1705 arg1 glycoproteins 1693:1705 two glycoproteins 1689:1705 two glycoproteins 1689:1705 Thus, two glycoproteins, AHSG and HPX, represent a pivotal glycoprotein of the cytoprotective activity for WN1316, showing a concrete evidence for the novel glycan-independent function of serum glycoproteins in neuroprotective drug efficacy. 29016670 10 41 gly glycoproteins 1693:1705 arg1 HPX 1717:1719 HPX 1717:1719 HPX 1717:1719 Thus, two glycoproteins, AHSG and HPX, represent a pivotal glycoprotein of the cytoprotective activity for WN1316, showing a concrete evidence for the novel glycan-independent function of serum glycoproteins in neuroprotective drug efficacy. 29016670 10 41 gly glycoproteins 1693:1705 arg1 AHSG 1708:1711 AHSG 1708:1711 AHSG 1708:1711 Thus, two glycoproteins, AHSG and HPX, represent a pivotal glycoprotein of the cytoprotective activity for WN1316, showing a concrete evidence for the novel glycan-independent function of serum glycoproteins in neuroprotective drug efficacy. 29016670 8 42 theme serum 1355:1359 arg1 proteins 1361:1368 fetal bovine serum proteins 1342:1368 fetal bovine serum proteins 1342:1368 In this study, we sieved through fetal bovine serum proteins and identified two N-linked glycoproteins, alpha-2-HS-glycoprotein (AHSG) and hemopexin (HPX), requisites to exert the WN1316 cytoprotective activity against oxidative injury in neuronal cells in vitro. 29016670 2 43 theme drugs 341:345 arg1 number 321:326 a limited number 311:326 a limited number of effective drugs for the treatment of neurological diseases 311:388 However, a limited number of effective drugs for the treatment of neurological diseases has been developed thus far. 29016670 3 44 theme therapeutic 473:483 arg1 agents 485:490 such therapeutic agents 468:490 such therapeutic agents 468:490 Further, the pharmacological mechanisms by which such therapeutic agents can protect neurons from cell death have not been fully understood. 29016670 5 45 from doses 936:940 arg1 models 955:960 ALS mouse models 945:960 ALS mouse models 945:960 One of the remarkable characteristics of WN1316 is that its efficacious doses in ALS mouse models are much less than those against oxidative injury in cultured human neuronal cells. 29016670 0 46 gly glycoproteins 29:41 arg1 glycoproteins 29:41 N-linked glycoproteins 20:41 N-linked glycoproteins 20:41 A novel function of N-linked glycoproteins, alpha-2-HS-glycoprotein and hemopexin: Implications for small molecule compound-mediated neuroprotection. 29016670 0 46 gly glycoproteins 29:41 arg1 hemopexin 72:80 hemopexin 72:80 hemopexin 72:80 A novel function of N-linked glycoproteins, alpha-2-HS-glycoprotein and hemopexin: Implications for small molecule compound-mediated neuroprotection. 29016670 0 46 gly glycoproteins 29:41 arg1 alpha-2-HS-glycoprotein 44:66 alpha-2-HS-glycoprotein 44:66 alpha-2-HS-glycoprotein 44:66 A novel function of N-linked glycoproteins, alpha-2-HS-glycoprotein and hemopexin: Implications for small molecule compound-mediated neuroprotection. 29016670 6 47 theme WN1316 1072:1077 arg1 dependent 1141:1149 dependent 1141:1149 dependent 1141:1149 It is also noted that the WN1316 cytoprotective activity observed in cultured cells is totally dependent upon the addition of fetal bovine serum in culture medium. 29016670 6 47 theme WN1316 1072:1077 arg1 activity 1094:1101 the WN1316 cytoprotective activity 1068:1101 the WN1316 cytoprotective activity observed in cultured cells 1068:1128 It is also noted that the WN1316 cytoprotective activity observed in cultured cells is totally dependent upon the addition of fetal bovine serum in culture medium. 29016670 8 48 theme neuronal 1548:1555 arg1 cells 1557:1561 neuronal cells 1548:1561 neuronal cells 1548:1561 In this study, we sieved through fetal bovine serum proteins and identified two N-linked glycoproteins, alpha-2-HS-glycoprotein (AHSG) and hemopexin (HPX), requisites to exert the WN1316 cytoprotective activity against oxidative injury in neuronal cells in vitro. 29016670 7 49 attach linked 1278:1283 arg1 efficacy 1299:1306 the WN1316 efficacy 1288:1306 the WN1316 efficacy 1288:1306 These findings led us to postulate some serum factors being tightly linked to the WN1316 efficacy. 29016670 7 49 attach linked 1278:1283 arg2 factors 1256:1262 some serum factors 1245:1262 some serum factors being tightly linked to the WN1316 efficacy 1245:1306 These findings led us to postulate some serum factors being tightly linked to the WN1316 efficacy. 29016670 4 50 theme promising 789:797 arg1 compound 613:620 the novel small-molecule compound 588:620 the novel small-molecule compound 588:620 We have previously reported the novel small-molecule compound, 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316), as a unique neuroprotectant against oxidative injury and a highly promising remedy for the treatment of amyotrophic lateral sclerosis (ALS). 29016670 4 50 theme promising 789:797 arg1 remedy 799:804 a highly promising remedy 780:804 a highly promising remedy for the treatment of amyotrophic lateral sclerosis (ALS) 780:861 We have previously reported the novel small-molecule compound, 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316), as a unique neuroprotectant against oxidative injury and a highly promising remedy for the treatment of amyotrophic lateral sclerosis (ALS). 29016670 3 51 theme cell 517:520 arg1 death 522:526 cell death 517:526 cell death 517:526 Further, the pharmacological mechanisms by which such therapeutic agents can protect neurons from cell death have not been fully understood. 29016670 0 52 gly alpha-2-HS-glycoprotein 44:66 arg1 glycoproteins 29:41 N-linked glycoproteins 20:41 N-linked glycoproteins 20:41 A novel function of N-linked glycoproteins, alpha-2-HS-glycoprotein and hemopexin: Implications for small molecule compound-mediated neuroprotection. 29016670 0 52 gly alpha-2-HS-glycoprotein 44:66 arg1 alpha-2-HS-glycoprotein 44:66 alpha-2-HS-glycoprotein 44:66 alpha-2-HS-glycoprotein 44:66 A novel function of N-linked glycoproteins, alpha-2-HS-glycoprotein and hemopexin: Implications for small molecule compound-mediated neuroprotection. 29016670 10 53 theme glycan-independent 1840:1857 arg1 function 1859:1866 the novel glycan-independent function 1830:1866 the novel glycan-independent function of serum glycoproteins in neuroprotective drug efficacy 1830:1922 Thus, two glycoproteins, AHSG and HPX, represent a pivotal glycoprotein of the cytoprotective activity for WN1316, showing a concrete evidence for the novel glycan-independent function of serum glycoproteins in neuroprotective drug efficacy. 29016670 8 54 from activity 1511:1518 arg1 cells 1557:1561 neuronal cells 1548:1561 neuronal cells 1548:1561 In this study, we sieved through fetal bovine serum proteins and identified two N-linked glycoproteins, alpha-2-HS-glycoprotein (AHSG) and hemopexin (HPX), requisites to exert the WN1316 cytoprotective activity against oxidative injury in neuronal cells in vitro. 29016670 1 55 theme action 260:265 arg1 action 260:265 action 260:265 action 260:265 Therapeutic agents to the central nervous system (CNS) need to be efficiently delivered to the target site of action at appropriate therapeutic levels. 29016670 1 55 theme action 260:265 arg1 site 252:255 the target site 241:255 the target site of action at appropriate therapeutic levels 241:299 Therapeutic agents to the central nervous system (CNS) need to be efficiently delivered to the target site of action at appropriate therapeutic levels. 29016670 9 56 theme chains 1604:1609 arg1 removal 1586:1592 the removal 1582:1592 the removal of glycan chains from these molecules 1582:1630 Notably, the removal of glycan chains from these molecules did not affect the WN1316 cytoprotective activity. 29016670 10 57 theme glycoproteins 1877:1889 arg1 function 1859:1866 the novel glycan-independent function 1830:1866 the novel glycan-independent function of serum glycoproteins in neuroprotective drug efficacy 1830:1922 Thus, two glycoproteins, AHSG and HPX, represent a pivotal glycoprotein of the cytoprotective activity for WN1316, showing a concrete evidence for the novel glycan-independent function of serum glycoproteins in neuroprotective drug efficacy. 29016670 1 58 from levels 294:299 arg1 action 260:265 action 260:265 action 260:265 Therapeutic agents to the central nervous system (CNS) need to be efficiently delivered to the target site of action at appropriate therapeutic levels. 29016670 1 58 from levels 294:299 arg1 site 252:255 the target site 241:255 the target site of action at appropriate therapeutic levels 241:299 Therapeutic agents to the central nervous system (CNS) need to be efficiently delivered to the target site of action at appropriate therapeutic levels. 29016670 2 59 theme limited 313:319 arg1 number 321:326 a limited number 311:326 a limited number of effective drugs for the treatment of neurological diseases 311:388 However, a limited number of effective drugs for the treatment of neurological diseases has been developed thus far. 29016670 9 60 from molecules 1622:1630 arg1 removal 1586:1592 the removal 1582:1592 the removal of glycan chains from these molecules 1582:1630 Notably, the removal of glycan chains from these molecules did not affect the WN1316 cytoprotective activity. 29016670 4 61 theme lateral 839:845 arg1 ALS 858:860 ALS 858:860 ALS 858:860 We have previously reported the novel small-molecule compound, 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316), as a unique neuroprotectant against oxidative injury and a highly promising remedy for the treatment of amyotrophic lateral sclerosis (ALS). 29016670 4 61 theme lateral 839:845 arg1 sclerosis 847:855 amyotrophic lateral sclerosis 827:855 amyotrophic lateral sclerosis (ALS) 827:861 We have previously reported the novel small-molecule compound, 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316), as a unique neuroprotectant against oxidative injury and a highly promising remedy for the treatment of amyotrophic lateral sclerosis (ALS). 29016670 5 62 from injury 1005:1010 arg1 cells 1039:1043 cultured human neuronal cells 1015:1043 cultured human neuronal cells 1015:1043 One of the remarkable characteristics of WN1316 is that its efficacious doses in ALS mouse models are much less than those against oxidative injury in cultured human neuronal cells. 29016670 5 63 theme remarkable 875:884 arg1 characteristics 886:900 the remarkable characteristics 871:900 the remarkable characteristics of WN1316 871:910 One of the remarkable characteristics of WN1316 is that its efficacious doses in ALS mouse models are much less than those against oxidative injury in cultured human neuronal cells. 29016670 10 64 theme neuroprotective 1894:1908 arg1 efficacy 1915:1922 neuroprotective drug efficacy 1894:1922 neuroprotective drug efficacy 1894:1922 Thus, two glycoproteins, AHSG and HPX, represent a pivotal glycoprotein of the cytoprotective activity for WN1316, showing a concrete evidence for the novel glycan-independent function of serum glycoproteins in neuroprotective drug efficacy. 29016670 9 65 theme WN1316 1651:1656 arg1 activity 1673:1680 the WN1316 cytoprotective activity 1647:1680 the WN1316 cytoprotective activity 1647:1680 Notably, the removal of glycan chains from these molecules did not affect the WN1316 cytoprotective activity. 29016670 6 66 theme culture 1194:1200 arg1 medium 1202:1207 culture medium 1194:1207 culture medium 1194:1207 It is also noted that the WN1316 cytoprotective activity observed in cultured cells is totally dependent upon the addition of fetal bovine serum in culture medium. 29016670 5 67 theme characteristics 886:900 arg1 One 864:866 One 864:866 One 864:866 One of the remarkable characteristics of WN1316 is that its efficacious doses in ALS mouse models are much less than those against oxidative injury in cultured human neuronal cells. 29016670 5 67 theme characteristics 886:900 arg1 characteristics 886:900 the remarkable characteristics 871:900 the remarkable characteristics of WN1316 871:910 One of the remarkable characteristics of WN1316 is that its efficacious doses in ALS mouse models are much less than those against oxidative injury in cultured human neuronal cells. 29016670 10 68 from glycoproteins 1877:1889 arg1 efficacy 1915:1922 neuroprotective drug efficacy 1894:1922 neuroprotective drug efficacy 1894:1922 Thus, two glycoproteins, AHSG and HPX, represent a pivotal glycoprotein of the cytoprotective activity for WN1316, showing a concrete evidence for the novel glycan-independent function of serum glycoproteins in neuroprotective drug efficacy. 29016670 6 69 theme serum 1185:1189 arg1 addition 1160:1167 the addition 1156:1167 the addition of fetal bovine serum in culture medium 1156:1207 It is also noted that the WN1316 cytoprotective activity observed in cultured cells is totally dependent upon the addition of fetal bovine serum in culture medium. 29016670 5 70 theme cultured 1015:1022 arg1 cells 1039:1043 cultured human neuronal cells 1015:1043 cultured human neuronal cells 1015:1043 One of the remarkable characteristics of WN1316 is that its efficacious doses in ALS mouse models are much less than those against oxidative injury in cultured human neuronal cells. 29016670 10 71 theme activity 1777:1784 arg1 glycoprotein 1742:1753 a pivotal glycoprotein 1732:1753 a pivotal glycoprotein of the cytoprotective activity for WN1316 1732:1795 Thus, two glycoproteins, AHSG and HPX, represent a pivotal glycoprotein of the cytoprotective activity for WN1316, showing a concrete evidence for the novel glycan-independent function of serum glycoproteins in neuroprotective drug efficacy. 29016670 1 72 theme Therapeutic 150:160 arg1 agents 162:167 Therapeutic agents 150:167 Therapeutic agents to the central nervous system (CNS) 150:203 Therapeutic agents to the central nervous system (CNS) need to be efficiently delivered to the target site of action at appropriate therapeutic levels. 29016670 6 73 theme fetal 1172:1176 arg1 serum 1185:1189 fetal bovine serum 1172:1189 fetal bovine serum 1172:1189 It is also noted that the WN1316 cytoprotective activity observed in cultured cells is totally dependent upon the addition of fetal bovine serum in culture medium. 29016670 5 74 theme neuronal 1030:1037 arg1 cells 1039:1043 cultured human neuronal cells 1015:1043 cultured human neuronal cells 1015:1043 One of the remarkable characteristics of WN1316 is that its efficacious doses in ALS mouse models are much less than those against oxidative injury in cultured human neuronal cells. 29016670 1 75 theme central 176:182 arg1 CNS 200:202 CNS 200:202 CNS 200:202 Therapeutic agents to the central nervous system (CNS) need to be efficiently delivered to the target site of action at appropriate therapeutic levels. 29016670 1 75 theme central 176:182 arg1 system 192:197 the central nervous system 172:197 the central nervous system (CNS) 172:203 Therapeutic agents to the central nervous system (CNS) need to be efficiently delivered to the target site of action at appropriate therapeutic levels. 29016670 0 76 theme small 100:104 arg1 neuroprotection 133:147 small molecule compound-mediated neuroprotection 100:147 small molecule compound-mediated neuroprotection 100:147 A novel function of N-linked glycoproteins, alpha-2-HS-glycoprotein and hemopexin: Implications for small molecule compound-mediated neuroprotection. 29016670 0 77 dep function 8:15 arg1 Implications 83:94 Implications 83:94 A novel function of N-linked glycoproteins, alpha-2-HS-glycoprotein and hemopexin: Implications for small molecule compound-mediated neuroprotection. 0:148 A novel function of N-linked glycoproteins, alpha-2-HS-glycoprotein and hemopexin: Implications for small molecule compound-mediated neuroprotection. 29016670 0 78 theme compound-mediated 115:131 arg1 neuroprotection 133:147 small molecule compound-mediated neuroprotection 100:147 small molecule compound-mediated neuroprotection 100:147 A novel function of N-linked glycoproteins, alpha-2-HS-glycoprotein and hemopexin: Implications for small molecule compound-mediated neuroprotection. 29016670 5 79 theme mouse 949:953 arg1 models 955:960 ALS mouse models 945:960 ALS mouse models 945:960 One of the remarkable characteristics of WN1316 is that its efficacious doses in ALS mouse models are much less than those against oxidative injury in cultured human neuronal cells. 29016670 4 80 theme oxidative 759:767 arg1 injury 769:774 oxidative injury 759:774 oxidative injury 759:774 We have previously reported the novel small-molecule compound, 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316), as a unique neuroprotectant against oxidative injury and a highly promising remedy for the treatment of amyotrophic lateral sclerosis (ALS). 29016670 3 81 theme pharmacological 432:446 arg1 mechanisms 448:457 the pharmacological mechanisms 428:457 the pharmacological mechanisms by which such therapeutic agents can protect neurons from cell death 428:526 Further, the pharmacological mechanisms by which such therapeutic agents can protect neurons from cell death have not been fully understood. 29016670 0 82 theme novel 2:6 arg1 function 8:15 A novel function 0:15 A novel function of N-linked glycoproteins, alpha-2-HS-glycoprotein and hemopexin: Implications for small molecule compound-mediated neuroprotection. 0:148 A novel function of N-linked glycoproteins, alpha-2-HS-glycoprotein and hemopexin: Implications for small molecule compound-mediated neuroprotection. 29016670 8 83 theme WN1316 1489:1494 arg1 activity 1511:1518 the WN1316 cytoprotective activity 1485:1518 the WN1316 cytoprotective activity against oxidative injury in neuronal cells 1485:1561 In this study, we sieved through fetal bovine serum proteins and identified two N-linked glycoproteins, alpha-2-HS-glycoprotein (AHSG) and hemopexin (HPX), requisites to exert the WN1316 cytoprotective activity against oxidative injury in neuronal cells in vitro. 29016670 2 84 theme neurological 368:379 arg1 diseases 381:388 neurological diseases 368:388 neurological diseases 368:388 However, a limited number of effective drugs for the treatment of neurological diseases has been developed thus far. 29016670 1 85 theme therapeutic 282:292 arg1 levels 294:299 appropriate therapeutic levels 270:299 appropriate therapeutic levels 270:299 Therapeutic agents to the central nervous system (CNS) need to be efficiently delivered to the target site of action at appropriate therapeutic levels. 29016670 5 86 theme efficacious 924:934 arg1 doses 936:940 its efficacious doses 920:940 its efficacious doses in ALS mouse models 920:960 One of the remarkable characteristics of WN1316 is that its efficacious doses in ALS mouse models are much less than those against oxidative injury in cultured human neuronal cells. 29016670 3 87 theme such 468:471 arg1 agents 485:490 such therapeutic agents 468:490 such therapeutic agents 468:490 Further, the pharmacological mechanisms by which such therapeutic agents can protect neurons from cell death have not been fully understood. 29016670 0 88 theme glycoproteins 29:41 arg1 function 8:15 A novel function 0:15 A novel function of N-linked glycoproteins, alpha-2-HS-glycoprotein and hemopexin: Implications for small molecule compound-mediated neuroprotection. 0:148 A novel function of N-linked glycoproteins, alpha-2-HS-glycoprotein and hemopexin: Implications for small molecule compound-mediated neuroprotection. 29016670 7 89 theme serum 1250:1254 arg1 factors 1256:1262 some serum factors 1245:1262 some serum factors being tightly linked to the WN1316 efficacy 1245:1306 These findings led us to postulate some serum factors being tightly linked to the WN1316 efficacy. 29016670 8 90 theme oxidative 1528:1536 arg1 injury 1538:1543 oxidative injury 1528:1543 oxidative injury 1528:1543 In this study, we sieved through fetal bovine serum proteins and identified two N-linked glycoproteins, alpha-2-HS-glycoprotein (AHSG) and hemopexin (HPX), requisites to exert the WN1316 cytoprotective activity against oxidative injury in neuronal cells in vitro. 29016670 5 91 theme oxidative 995:1003 arg1 injury 1005:1010 oxidative injury 995:1010 oxidative injury in cultured human neuronal cells 995:1043 One of the remarkable characteristics of WN1316 is that its efficacious doses in ALS mouse models are much less than those against oxidative injury in cultured human neuronal cells. 29016670 8 92 theme bovine 1348:1353 arg1 proteins 1361:1368 fetal bovine serum proteins 1342:1368 fetal bovine serum proteins 1342:1368 In this study, we sieved through fetal bovine serum proteins and identified two N-linked glycoproteins, alpha-2-HS-glycoprotein (AHSG) and hemopexin (HPX), requisites to exert the WN1316 cytoprotective activity against oxidative injury in neuronal cells in vitro. 29016670 2 93 theme effective 331:339 arg1 drugs 341:345 effective drugs 331:345 effective drugs for the treatment of neurological diseases 331:388 However, a limited number of effective drugs for the treatment of neurological diseases has been developed thus far. 29016670 6 94 theme cytoprotective 1079:1092 arg1 dependent 1141:1149 dependent 1141:1149 dependent 1141:1149 It is also noted that the WN1316 cytoprotective activity observed in cultured cells is totally dependent upon the addition of fetal bovine serum in culture medium. 29016670 6 94 theme cytoprotective 1079:1092 arg1 activity 1094:1101 the WN1316 cytoprotective activity 1068:1101 the WN1316 cytoprotective activity observed in cultured cells 1068:1128 It is also noted that the WN1316 cytoprotective activity observed in cultured cells is totally dependent upon the addition of fetal bovine serum in culture medium. 29016670 10 95 theme concrete 1808:1815 arg1 evidence 1817:1824 a concrete evidence 1806:1824 a concrete evidence for the novel glycan-independent function of serum glycoproteins in neuroprotective drug efficacy 1806:1922 Thus, two glycoproteins, AHSG and HPX, represent a pivotal glycoprotein of the cytoprotective activity for WN1316, showing a concrete evidence for the novel glycan-independent function of serum glycoproteins in neuroprotective drug efficacy. 29016670 4 96 theme 2-[mesityl 623:632 arg1 compound 613:620 the novel small-molecule compound 588:620 the novel small-molecule compound 588:620 We have previously reported the novel small-molecule compound, 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316), as a unique neuroprotectant against oxidative injury and a highly promising remedy for the treatment of amyotrophic lateral sclerosis (ALS). 29016670 4 96 theme 2-[mesityl 623:632 arg1 trihydrochloride 696:711 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316) 623:720 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316) 623:720 We have previously reported the novel small-molecule compound, 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316), as a unique neuroprotectant against oxidative injury and a highly promising remedy for the treatment of amyotrophic lateral sclerosis (ALS). 29016670 1 97 theme target 245:250 arg1 action 260:265 action 260:265 action 260:265 Therapeutic agents to the central nervous system (CNS) need to be efficiently delivered to the target site of action at appropriate therapeutic levels. 29016670 1 97 theme target 245:250 arg1 site 252:255 the target site 241:255 the target site of action at appropriate therapeutic levels 241:299 Therapeutic agents to the central nervous system (CNS) need to be efficiently delivered to the target site of action at appropriate therapeutic levels. 27189951 1 0 theme poly-N-acetyllactosamine-containing 284:318 arg1 structures 320:329 some exceptionally large poly-N-acetyllactosamine-containing structures 259:329 some exceptionally large poly-N-acetyllactosamine-containing structures 259:329 The bloodstream form of the human pathogen Trypanosoma brucei expresses oligomannose, paucimannose, and complex N-linked glycans, including some exceptionally large poly-N-acetyllactosamine-containing structures. 27189951 10 1 theme β1-2 1986:1989 arg1 linkages 2002:2009 β1-2 glycosidic linkages 1986:2009 β1-2 glycosidic linkages 1986:2009 These results provide further detail on the structure and biosynthesis of complex N-glycans in an important human pathogen and provide a second example of the adaptation by trypanosomes of β3-glycosyltransferase family members to catalyze β1-2 glycosidic linkages. 27189951 3 2 theme arms 598:601 arg1 elaboration 559:569 the elaboration 555:569 the elaboration of the Manα1-3 and Manα1-6 arms, respectively, of the conserved trimannosyl-N-acetylchitobiosyl core of N-linked glycans 555:690 These genes encode the activities that initiate the elaboration of the Manα1-3 and Manα1-6 arms, respectively, of the conserved trimannosyl-N-acetylchitobiosyl core of N-linked glycans. 27189951 9 3 theme large 1392:1396 arg1 poly-N-acetyllactosamine 1398:1421 the large poly-N-acetyllactosamine 1388:1421 the large poly-N-acetyllactosamine containing N-glycans of the TbGnTII null mutants by methylation linkage analysis 1388:1502 Characterization of the large poly-N-acetyllactosamine containing N-glycans of the TbGnTII null mutants by methylation linkage analysis suggests that, in wild-type parasites, the Manα1-6 arm of the conserved trimannosyl core may carry predominantly linear poly-N-acetyllactosamine chains, whereas the Manα1-3 arm may carry predominantly branched poly-N-acetyllactosamine chains. 27189951 9 4 theme Manα1-3 1669:1675 arg1 arm 1677:1679 the Manα1-3 arm 1665:1679 the Manα1-3 arm 1665:1679 Characterization of the large poly-N-acetyllactosamine containing N-glycans of the TbGnTII null mutants by methylation linkage analysis suggests that, in wild-type parasites, the Manα1-6 arm of the conserved trimannosyl core may carry predominantly linear poly-N-acetyllactosamine chains, whereas the Manα1-3 arm may carry predominantly branched poly-N-acetyllactosamine chains. 27189951 10 5 theme further 1769:1775 arg1 detail 1777:1782 further detail 1769:1782 further detail on the structure and biosynthesis of complex N-glycans in an important human pathogen 1769:1868 These results provide further detail on the structure and biosynthesis of complex N-glycans in an important human pathogen and provide a second example of the adaptation by trypanosomes of β3-glycosyltransferase family members to catalyze β1-2 glycosidic linkages. 27189951 8 6 theme multicellular 1221:1233 arg1 organisms 1235:1243 multicellular organisms 1221:1243 multicellular organisms 1221:1243 In contrast to multicellular organisms, where GnTII activity is essential, TbGnTII null mutants of T. brucei grow in culture and are still infectious to animals. 27189951 4 7 theme glycosyltransferase 825:843 arg1 genes 845:849 putative T. brucei glycosyltransferase genes 806:849 putative T. brucei glycosyltransferase genes belonging to the β3-glycosyltransferase superfamily (Damerow, M., Rodrigues, J. A., Wu, D., Güther, M. L., Mehlert, A., and Ferguson, M. A. (2014) J. Biol 806:1004 Previously, we identified a highly divergent T. brucei N-acetylglucosaminyltransferase I (TbGnTI) among a set of putative T. brucei glycosyltransferase genes belonging to the β3-glycosyltransferase superfamily (Damerow, M., Rodrigues, J. A., Wu, D., Güther, M. L., Mehlert, A., and Ferguson, M. A. (2014) J. Biol. 27189951 3 8 theme conserved 625:633 arg1 core 667:670 the conserved trimannosyl-N-acetylchitobiosyl core 621:670 the conserved trimannosyl-N-acetylchitobiosyl core of N-linked glycans 621:690 These genes encode the activities that initiate the elaboration of the Manα1-3 and Manα1-6 arms, respectively, of the conserved trimannosyl-N-acetylchitobiosyl core of N-linked glycans. 27189951 2 9 theme complex 356:362 arg1 N-glycans 364:372 complex N-glycans 356:372 complex N-glycans 356:372 Despite the presence of complex N-glycans in this organism, no homologues of the canonical N-acetylglucosaminyltransferase I or II genes can be found in the T. brucei genome. 27189951 9 10 theme TbGnTII 1451:1457 arg1 mutants 1464:1470 the TbGnTII null mutants 1447:1470 the TbGnTII null mutants 1447:1470 Characterization of the large poly-N-acetyllactosamine containing N-glycans of the TbGnTII null mutants by methylation linkage analysis suggests that, in wild-type parasites, the Manα1-6 arm of the conserved trimannosyl core may carry predominantly linear poly-N-acetyllactosamine chains, whereas the Manα1-3 arm may carry predominantly branched poly-N-acetyllactosamine chains. 27189951 9 11 theme poly-N-acetyllactosamine 1714:1737 arg1 chains 1739:1744 predominantly branched poly-N-acetyllactosamine chains 1691:1744 predominantly branched poly-N-acetyllactosamine chains 1691:1744 Characterization of the large poly-N-acetyllactosamine containing N-glycans of the TbGnTII null mutants by methylation linkage analysis suggests that, in wild-type parasites, the Manα1-6 arm of the conserved trimannosyl core may carry predominantly linear poly-N-acetyllactosamine chains, whereas the Manα1-3 arm may carry predominantly branched poly-N-acetyllactosamine chains. 27189951 9 12 dep carry 1597:1601 arg1 whereas 1657:1663 whereas 1657:1663 whereas 1657:1663 Characterization of the large poly-N-acetyllactosamine containing N-glycans of the TbGnTII null mutants by methylation linkage analysis suggests that, in wild-type parasites, the Manα1-6 arm of the conserved trimannosyl core may carry predominantly linear poly-N-acetyllactosamine chains, whereas the Manα1-3 arm may carry predominantly branched poly-N-acetyllactosamine chains. 27189951 3 13 theme core 667:670 arg1 core 667:670 the conserved trimannosyl-N-acetylchitobiosyl core 621:670 the conserved trimannosyl-N-acetylchitobiosyl core of N-linked glycans 621:690 These genes encode the activities that initiate the elaboration of the Manα1-3 and Manα1-6 arms, respectively, of the conserved trimannosyl-N-acetylchitobiosyl core of N-linked glycans. 27189951 3 13 theme core 667:670 arg1 arms 598:601 the Manα1-3 and Manα1-6 arms 574:601 arms 598:601 These genes encode the activities that initiate the elaboration of the Manα1-3 and Manα1-6 arms, respectively, of the conserved trimannosyl-N-acetylchitobiosyl core of N-linked glycans. 27189951 9 14 theme mutants 1464:1470 arg1 N-glycans 1434:1442 N-glycans 1434:1442 N-glycans of the TbGnTII null mutants by methylation linkage analysis 1434:1502 Characterization of the large poly-N-acetyllactosamine containing N-glycans of the TbGnTII null mutants by methylation linkage analysis suggests that, in wild-type parasites, the Manα1-6 arm of the conserved trimannosyl core may carry predominantly linear poly-N-acetyllactosamine chains, whereas the Manα1-3 arm may carry predominantly branched poly-N-acetyllactosamine chains. 27189951 9 15 contain carry 1597:1601 arg1 core 1588:1591 the conserved trimannosyl core 1562:1591 the conserved trimannosyl core 1562:1591 Characterization of the large poly-N-acetyllactosamine containing N-glycans of the TbGnTII null mutants by methylation linkage analysis suggests that, in wild-type parasites, the Manα1-6 arm of the conserved trimannosyl core may carry predominantly linear poly-N-acetyllactosamine chains, whereas the Manα1-3 arm may carry predominantly branched poly-N-acetyllactosamine chains. 27189951 9 15 contain carry 1597:1601 arg1 arm 1555:1557 the Manα1-6 arm 1543:1557 the Manα1-6 arm of the conserved trimannosyl core 1543:1591 Characterization of the large poly-N-acetyllactosamine containing N-glycans of the TbGnTII null mutants by methylation linkage analysis suggests that, in wild-type parasites, the Manα1-6 arm of the conserved trimannosyl core may carry predominantly linear poly-N-acetyllactosamine chains, whereas the Manα1-3 arm may carry predominantly branched poly-N-acetyllactosamine chains. 27189951 9 15 contain carry 1597:1601 arg3 parasites 1532:1540 wild-type parasites 1522:1540 wild-type parasites 1522:1540 Characterization of the large poly-N-acetyllactosamine containing N-glycans of the TbGnTII null mutants by methylation linkage analysis suggests that, in wild-type parasites, the Manα1-6 arm of the conserved trimannosyl core may carry predominantly linear poly-N-acetyllactosamine chains, whereas the Manα1-3 arm may carry predominantly branched poly-N-acetyllactosamine chains. 27189951 9 15 contain carry 1597:1601 arg2 chains 1649:1654 predominantly linear poly-N-acetyllactosamine chains 1603:1654 predominantly linear poly-N-acetyllactosamine chains 1603:1654 Characterization of the large poly-N-acetyllactosamine containing N-glycans of the TbGnTII null mutants by methylation linkage analysis suggests that, in wild-type parasites, the Manα1-6 arm of the conserved trimannosyl core may carry predominantly linear poly-N-acetyllactosamine chains, whereas the Manα1-3 arm may carry predominantly branched poly-N-acetyllactosamine chains. 27189951 10 16 theme complex 1821:1827 arg1 N-glycans 1829:1837 complex N-glycans 1821:1837 complex N-glycans 1821:1837 These results provide further detail on the structure and biosynthesis of complex N-glycans in an important human pathogen and provide a second example of the adaptation by trypanosomes of β3-glycosyltransferase family members to catalyze β1-2 glycosidic linkages. 27189951 9 17 theme methylation 1475:1485 arg1 analysis 1495:1502 methylation linkage analysis 1475:1502 methylation linkage analysis 1475:1502 Characterization of the large poly-N-acetyllactosamine containing N-glycans of the TbGnTII null mutants by methylation linkage analysis suggests that, in wild-type parasites, the Manα1-6 arm of the conserved trimannosyl core may carry predominantly linear poly-N-acetyllactosamine chains, whereas the Manα1-3 arm may carry predominantly branched poly-N-acetyllactosamine chains. 27189951 10 18 from detail 1777:1782 arg1 biosynthesis 1805:1816 biosynthesis 1805:1816 biosynthesis 1805:1816 These results provide further detail on the structure and biosynthesis of complex N-glycans in an important human pathogen and provide a second example of the adaptation by trypanosomes of β3-glycosyltransferase family members to catalyze β1-2 glycosidic linkages. 27189951 10 18 from detail 1777:1782 arg1 pathogen 1861:1868 an important human pathogen 1842:1868 an important human pathogen 1842:1868 These results provide further detail on the structure and biosynthesis of complex N-glycans in an important human pathogen and provide a second example of the adaptation by trypanosomes of β3-glycosyltransferase family members to catalyze β1-2 glycosidic linkages. 27189951 10 18 from detail 1777:1782 arg1 structure 1791:1799 structure 1791:1799 structure 1791:1799 These results provide further detail on the structure and biosynthesis of complex N-glycans in an important human pathogen and provide a second example of the adaptation by trypanosomes of β3-glycosyltransferase family members to catalyze β1-2 glycosidic linkages. 27189951 1 19 theme human 147:151 arg1 brucei 174:179 the human pathogen Trypanosoma brucei 143:179 the human pathogen Trypanosoma brucei 143:179 The bloodstream form of the human pathogen Trypanosoma brucei expresses oligomannose, paucimannose, and complex N-linked glycans, including some exceptionally large poly-N-acetyllactosamine-containing structures. 27189951 4 20 theme N-acetylglucosaminyltransferase 748:778 arg1 I 780:780 a highly divergent T. brucei N-acetylglucosaminyltransferase I 719:780 a highly divergent T. brucei N-acetylglucosaminyltransferase I (TbGnTI) 719:789 Previously, we identified a highly divergent T. brucei N-acetylglucosaminyltransferase I (TbGnTI) among a set of putative T. brucei glycosyltransferase genes belonging to the β3-glycosyltransferase superfamily (Damerow, M., Rodrigues, J. A., Wu, D., Güther, M. L., Mehlert, A., and Ferguson, M. A. (2014) J. Biol. 27189951 4 20 theme N-acetylglucosaminyltransferase 748:778 arg1 TbGnTI 783:788 TbGnTI 783:788 TbGnTI 783:788 Previously, we identified a highly divergent T. brucei N-acetylglucosaminyltransferase I (TbGnTI) among a set of putative T. brucei glycosyltransferase genes belonging to the β3-glycosyltransferase superfamily (Damerow, M., Rodrigues, J. A., Wu, D., Güther, M. L., Mehlert, A., and Ferguson, M. A. (2014) J. Biol. 27189951 3 21 theme N-linked 675:682 arg1 glycans 684:690 N-linked glycans 675:690 N-linked glycans 675:690 These genes encode the activities that initiate the elaboration of the Manα1-3 and Manα1-6 arms, respectively, of the conserved trimannosyl-N-acetylchitobiosyl core of N-linked glycans. 27189951 1 22 theme Trypanosoma 162:172 arg1 brucei 174:179 the human pathogen Trypanosoma brucei 143:179 the human pathogen Trypanosoma brucei 143:179 The bloodstream form of the human pathogen Trypanosoma brucei expresses oligomannose, paucimannose, and complex N-linked glycans, including some exceptionally large poly-N-acetyllactosamine-containing structures. 27189951 1 23 link N-linked 231:238 arg1 structures 320:329 some exceptionally large poly-N-acetyllactosamine-containing structures 259:329 some exceptionally large poly-N-acetyllactosamine-containing structures 259:329 The bloodstream form of the human pathogen Trypanosoma brucei expresses oligomannose, paucimannose, and complex N-linked glycans, including some exceptionally large poly-N-acetyllactosamine-containing structures. 27189951 1 23 link N-linked 231:238 arg1 glycans 240:246 complex N-linked glycans 223:246 complex N-linked glycans 223:246 The bloodstream form of the human pathogen Trypanosoma brucei expresses oligomannose, paucimannose, and complex N-linked glycans, including some exceptionally large poly-N-acetyllactosamine-containing structures. 27189951 9 24 contain containing 1423:1432 arg1 poly-N-acetyllactosamine 1398:1421 the large poly-N-acetyllactosamine 1388:1421 the large poly-N-acetyllactosamine containing N-glycans of the TbGnTII null mutants by methylation linkage analysis 1388:1502 Characterization of the large poly-N-acetyllactosamine containing N-glycans of the TbGnTII null mutants by methylation linkage analysis suggests that, in wild-type parasites, the Manα1-6 arm of the conserved trimannosyl core may carry predominantly linear poly-N-acetyllactosamine chains, whereas the Manα1-3 arm may carry predominantly branched poly-N-acetyllactosamine chains. 27189951 9 24 contain containing 1423:1432 arg2 N-glycans 1434:1442 N-glycans 1434:1442 N-glycans of the TbGnTII null mutants by methylation linkage analysis 1434:1502 Characterization of the large poly-N-acetyllactosamine containing N-glycans of the TbGnTII null mutants by methylation linkage analysis suggests that, in wild-type parasites, the Manα1-6 arm of the conserved trimannosyl core may carry predominantly linear poly-N-acetyllactosamine chains, whereas the Manα1-3 arm may carry predominantly branched poly-N-acetyllactosamine chains. 27189951 6 25 dep 289 1013:1015 arg1 9328-9339 1018:1026 9328-9339 1018:1026 9328-9339 1018:1026 289, 9328-9339). 27189951 2 26 theme genes 463:467 arg1 homologues 395:404 no homologues 392:404 no homologues of the canonical N-acetylglucosaminyltransferase I or II genes 392:467 Despite the presence of complex N-glycans in this organism, no homologues of the canonical N-acetylglucosaminyltransferase I or II genes can be found in the T. brucei genome. 27189951 7 27 theme N-acetylglucosaminyltransferase 1151:1181 arg1 TbGT15 1056:1061 TbGT15 1056:1061 TbGT15 1056:1061 Here, we demonstrate that TbGT15, another member of the same β3-glycosyltransferase family, encodes an equally divergent N-acetylglucosaminyltransferase II (TbGnTII) activity. 27189951 7 27 theme N-acetylglucosaminyltransferase 1151:1181 arg1 activity 1196:1203 an equally divergent N-acetylglucosaminyltransferase II (TbGnTII) activity 1130:1203 an equally divergent N-acetylglucosaminyltransferase II (TbGnTII) activity 1130:1203 Here, we demonstrate that TbGT15, another member of the same β3-glycosyltransferase family, encodes an equally divergent N-acetylglucosaminyltransferase II (TbGnTII) activity. 27189951 0 28 theme Family 37:42 arg1 Gene 2:5 A Gene 0:5 A Gene of the β3-Glycosyltransferase Family 0:42 A Gene of the β3-Glycosyltransferase Family Encodes N-Acetylglucosaminyltransferase II Function in Trypanosoma brucei. 27189951 0 28 theme Family 37:42 arg1 Function 87:94 N-Acetylglucosaminyltransferase II Function 52:94 N-Acetylglucosaminyltransferase II Function in Trypanosoma brucei 52:116 A Gene of the β3-Glycosyltransferase Family Encodes N-Acetylglucosaminyltransferase II Function in Trypanosoma brucei. 27189951 8 29 dep organisms 1235:1243 arg1 contrast 1209:1216 contrast 1209:1216 contrast 1209:1216 In contrast to multicellular organisms, where GnTII activity is essential, TbGnTII null mutants of T. brucei grow in culture and are still infectious to animals. 27189951 2 30 theme T. 489:490 arg1 genome 499:504 the T. brucei genome 485:504 the T. brucei genome 485:504 Despite the presence of complex N-glycans in this organism, no homologues of the canonical N-acetylglucosaminyltransferase I or II genes can be found in the T. brucei genome. 27189951 4 31 theme T. 815:816 arg1 genes 845:849 putative T. brucei glycosyltransferase genes 806:849 putative T. brucei glycosyltransferase genes belonging to the β3-glycosyltransferase superfamily (Damerow, M., Rodrigues, J. A., Wu, D., Güther, M. L., Mehlert, A., and Ferguson, M. A. (2014) J. Biol 806:1004 Previously, we identified a highly divergent T. brucei N-acetylglucosaminyltransferase I (TbGnTI) among a set of putative T. brucei glycosyltransferase genes belonging to the β3-glycosyltransferase superfamily (Damerow, M., Rodrigues, J. A., Wu, D., Güther, M. L., Mehlert, A., and Ferguson, M. A. (2014) J. Biol. 27189951 9 32 contain carry 1685:1689 arg1 arm 1677:1679 the Manα1-3 arm 1665:1679 the Manα1-3 arm 1665:1679 Characterization of the large poly-N-acetyllactosamine containing N-glycans of the TbGnTII null mutants by methylation linkage analysis suggests that, in wild-type parasites, the Manα1-6 arm of the conserved trimannosyl core may carry predominantly linear poly-N-acetyllactosamine chains, whereas the Manα1-3 arm may carry predominantly branched poly-N-acetyllactosamine chains. 27189951 9 32 contain carry 1685:1689 arg2 chains 1739:1744 predominantly branched poly-N-acetyllactosamine chains 1691:1744 predominantly branched poly-N-acetyllactosamine chains 1691:1744 Characterization of the large poly-N-acetyllactosamine containing N-glycans of the TbGnTII null mutants by methylation linkage analysis suggests that, in wild-type parasites, the Manα1-6 arm of the conserved trimannosyl core may carry predominantly linear poly-N-acetyllactosamine chains, whereas the Manα1-3 arm may carry predominantly branched poly-N-acetyllactosamine chains. 27189951 9 33 theme null 1459:1462 arg1 mutants 1464:1470 the TbGnTII null mutants 1447:1470 the TbGnTII null mutants 1447:1470 Characterization of the large poly-N-acetyllactosamine containing N-glycans of the TbGnTII null mutants by methylation linkage analysis suggests that, in wild-type parasites, the Manα1-6 arm of the conserved trimannosyl core may carry predominantly linear poly-N-acetyllactosamine chains, whereas the Manα1-3 arm may carry predominantly branched poly-N-acetyllactosamine chains. 27189951 1 34 theme bloodstream 123:133 arg1 form 135:138 The bloodstream form 119:138 The bloodstream form of the human pathogen Trypanosoma brucei 119:179 The bloodstream form of the human pathogen Trypanosoma brucei expresses oligomannose, paucimannose, and complex N-linked glycans, including some exceptionally large poly-N-acetyllactosamine-containing structures. 27189951 8 35 theme null 1289:1292 arg1 mutants 1294:1300 TbGnTII null mutants 1281:1300 TbGnTII null mutants of T. brucei 1281:1313 In contrast to multicellular organisms, where GnTII activity is essential, TbGnTII null mutants of T. brucei grow in culture and are still infectious to animals. 27189951 10 36 theme second 1884:1889 arg1 example 1891:1897 a second example 1882:1897 a second example of the adaptation by trypanosomes of β3-glycosyltransferase family members to catalyze β1-2 glycosidic linkages 1882:2009 These results provide further detail on the structure and biosynthesis of complex N-glycans in an important human pathogen and provide a second example of the adaptation by trypanosomes of β3-glycosyltransferase family members to catalyze β1-2 glycosidic linkages. 27189951 0 37 theme β3-Glycosyltransferase 14:35 arg1 Family 37:42 the β3-Glycosyltransferase Family 10:42 the β3-Glycosyltransferase Family 10:42 A Gene of the β3-Glycosyltransferase Family Encodes N-Acetylglucosaminyltransferase II Function in Trypanosoma brucei. 27189951 7 38 theme family 1114:1119 arg1 TbGT15 1056:1061 TbGT15 1056:1061 TbGT15 1056:1061 Here, we demonstrate that TbGT15, another member of the same β3-glycosyltransferase family, encodes an equally divergent N-acetylglucosaminyltransferase II (TbGnTII) activity. 27189951 7 38 theme family 1114:1119 arg1 member 1072:1077 another member 1064:1077 another member of the same β3-glycosyltransferase family 1064:1119 Here, we demonstrate that TbGT15, another member of the same β3-glycosyltransferase family, encodes an equally divergent N-acetylglucosaminyltransferase II (TbGnTII) activity. 27189951 9 39 theme trimannosyl 1576:1586 arg1 core 1588:1591 the conserved trimannosyl core 1562:1591 the conserved trimannosyl core 1562:1591 Characterization of the large poly-N-acetyllactosamine containing N-glycans of the TbGnTII null mutants by methylation linkage analysis suggests that, in wild-type parasites, the Manα1-6 arm of the conserved trimannosyl core may carry predominantly linear poly-N-acetyllactosamine chains, whereas the Manα1-3 arm may carry predominantly branched poly-N-acetyllactosamine chains. 27189951 7 40 theme same 1086:1089 arg1 family 1114:1119 the same β3-glycosyltransferase family 1082:1119 the same β3-glycosyltransferase family 1082:1119 Here, we demonstrate that TbGT15, another member of the same β3-glycosyltransferase family, encodes an equally divergent N-acetylglucosaminyltransferase II (TbGnTII) activity. 27189951 10 41 theme important 1845:1853 arg1 pathogen 1861:1868 an important human pathogen 1842:1868 an important human pathogen 1842:1868 These results provide further detail on the structure and biosynthesis of complex N-glycans in an important human pathogen and provide a second example of the adaptation by trypanosomes of β3-glycosyltransferase family members to catalyze β1-2 glycosidic linkages. 27189951 10 42 theme adaptation 1906:1915 arg1 example 1891:1897 a second example 1882:1897 a second example of the adaptation by trypanosomes of β3-glycosyltransferase family members to catalyze β1-2 glycosidic linkages 1882:2009 These results provide further detail on the structure and biosynthesis of complex N-glycans in an important human pathogen and provide a second example of the adaptation by trypanosomes of β3-glycosyltransferase family members to catalyze β1-2 glycosidic linkages. 27189951 4 43 dep divergent 728:736 arg1 T. 738:739 T. 738:739 T. 738:739 Previously, we identified a highly divergent T. brucei N-acetylglucosaminyltransferase I (TbGnTI) among a set of putative T. brucei glycosyltransferase genes belonging to the β3-glycosyltransferase superfamily (Damerow, M., Rodrigues, J. A., Wu, D., Güther, M. L., Mehlert, A., and Ferguson, M. A. (2014) J. Biol. 27189951 2 44 theme N-acetylglucosaminyltransferase 423:453 arg1 genes 463:467 the canonical N-acetylglucosaminyltransferase I or II genes 409:467 the canonical N-acetylglucosaminyltransferase I or II genes 409:467 Despite the presence of complex N-glycans in this organism, no homologues of the canonical N-acetylglucosaminyltransferase I or II genes can be found in the T. brucei genome. 27189951 7 45 theme divergent 1141:1149 arg1 TbGT15 1056:1061 TbGT15 1056:1061 TbGT15 1056:1061 Here, we demonstrate that TbGT15, another member of the same β3-glycosyltransferase family, encodes an equally divergent N-acetylglucosaminyltransferase II (TbGnTII) activity. 27189951 7 45 theme divergent 1141:1149 arg1 activity 1196:1203 an equally divergent N-acetylglucosaminyltransferase II (TbGnTII) activity 1130:1203 an equally divergent N-acetylglucosaminyltransferase II (TbGnTII) activity 1130:1203 Here, we demonstrate that TbGT15, another member of the same β3-glycosyltransferase family, encodes an equally divergent N-acetylglucosaminyltransferase II (TbGnTII) activity. 27189951 9 46 theme poly-N-acetyllactosamine 1624:1647 arg1 chains 1649:1654 predominantly linear poly-N-acetyllactosamine chains 1603:1654 predominantly linear poly-N-acetyllactosamine chains 1603:1654 Characterization of the large poly-N-acetyllactosamine containing N-glycans of the TbGnTII null mutants by methylation linkage analysis suggests that, in wild-type parasites, the Manα1-6 arm of the conserved trimannosyl core may carry predominantly linear poly-N-acetyllactosamine chains, whereas the Manα1-3 arm may carry predominantly branched poly-N-acetyllactosamine chains. 27189951 10 47 theme β3-glycosyltransferase 1936:1957 arg1 members 1966:1972 β3-glycosyltransferase family members 1936:1972 β3-glycosyltransferase family members 1936:1972 These results provide further detail on the structure and biosynthesis of complex N-glycans in an important human pathogen and provide a second example of the adaptation by trypanosomes of β3-glycosyltransferase family members to catalyze β1-2 glycosidic linkages. 27189951 1 48 theme large 278:282 arg1 structures 320:329 some exceptionally large poly-N-acetyllactosamine-containing structures 259:329 some exceptionally large poly-N-acetyllactosamine-containing structures 259:329 The bloodstream form of the human pathogen Trypanosoma brucei expresses oligomannose, paucimannose, and complex N-linked glycans, including some exceptionally large poly-N-acetyllactosamine-containing structures. 27189951 3 49 theme Manα1-6 590:596 arg1 core 667:670 the conserved trimannosyl-N-acetylchitobiosyl core 621:670 the conserved trimannosyl-N-acetylchitobiosyl core of N-linked glycans 621:690 These genes encode the activities that initiate the elaboration of the Manα1-3 and Manα1-6 arms, respectively, of the conserved trimannosyl-N-acetylchitobiosyl core of N-linked glycans. 27189951 3 49 theme Manα1-6 590:596 arg1 arms 598:601 the Manα1-3 and Manα1-6 arms 574:601 arms 598:601 These genes encode the activities that initiate the elaboration of the Manα1-3 and Manα1-6 arms, respectively, of the conserved trimannosyl-N-acetylchitobiosyl core of N-linked glycans. 27189951 3 50 theme Manα1-3 578:584 arg1 core 667:670 the conserved trimannosyl-N-acetylchitobiosyl core 621:670 the conserved trimannosyl-N-acetylchitobiosyl core of N-linked glycans 621:690 These genes encode the activities that initiate the elaboration of the Manα1-3 and Manα1-6 arms, respectively, of the conserved trimannosyl-N-acetylchitobiosyl core of N-linked glycans. 27189951 3 50 theme Manα1-3 578:584 arg1 arms 598:601 the Manα1-3 and Manα1-6 arms 574:601 arms 598:601 These genes encode the activities that initiate the elaboration of the Manα1-3 and Manα1-6 arms, respectively, of the conserved trimannosyl-N-acetylchitobiosyl core of N-linked glycans. 27189951 9 51 theme poly-N-acetyllactosamine 1398:1421 arg1 Characterization 1368:1383 Characterization 1368:1383 Characterization of the large poly-N-acetyllactosamine containing N-glycans of the TbGnTII null mutants by methylation linkage analysis 1368:1502 Characterization of the large poly-N-acetyllactosamine containing N-glycans of the TbGnTII null mutants by methylation linkage analysis suggests that, in wild-type parasites, the Manα1-6 arm of the conserved trimannosyl core may carry predominantly linear poly-N-acetyllactosamine chains, whereas the Manα1-3 arm may carry predominantly branched poly-N-acetyllactosamine chains. 27189951 10 52 theme members 1966:1972 arg1 trypanosomes 1920:1931 trypanosomes 1920:1931 trypanosomes of β3-glycosyltransferase family members 1920:1972 These results provide further detail on the structure and biosynthesis of complex N-glycans in an important human pathogen and provide a second example of the adaptation by trypanosomes of β3-glycosyltransferase family members to catalyze β1-2 glycosidic linkages. 27189951 4 53 theme divergent 728:736 arg1 I 780:780 a highly divergent T. brucei N-acetylglucosaminyltransferase I 719:780 a highly divergent T. brucei N-acetylglucosaminyltransferase I (TbGnTI) 719:789 Previously, we identified a highly divergent T. brucei N-acetylglucosaminyltransferase I (TbGnTI) among a set of putative T. brucei glycosyltransferase genes belonging to the β3-glycosyltransferase superfamily (Damerow, M., Rodrigues, J. A., Wu, D., Güther, M. L., Mehlert, A., and Ferguson, M. A. (2014) J. Biol. 27189951 4 53 theme divergent 728:736 arg1 TbGnTI 783:788 TbGnTI 783:788 TbGnTI 783:788 Previously, we identified a highly divergent T. brucei N-acetylglucosaminyltransferase I (TbGnTI) among a set of putative T. brucei glycosyltransferase genes belonging to the β3-glycosyltransferase superfamily (Damerow, M., Rodrigues, J. A., Wu, D., Güther, M. L., Mehlert, A., and Ferguson, M. A. (2014) J. Biol. 27189951 2 54 theme N-glycans 364:372 arg1 presence 344:351 the presence 340:351 the presence of complex N-glycans in this organism 340:389 Despite the presence of complex N-glycans in this organism, no homologues of the canonical N-acetylglucosaminyltransferase I or II genes can be found in the T. brucei genome. 27189951 9 55 theme branched 1705:1712 arg1 chains 1739:1744 predominantly branched poly-N-acetyllactosamine chains 1691:1744 predominantly branched poly-N-acetyllactosamine chains 1691:1744 Characterization of the large poly-N-acetyllactosamine containing N-glycans of the TbGnTII null mutants by methylation linkage analysis suggests that, in wild-type parasites, the Manα1-6 arm of the conserved trimannosyl core may carry predominantly linear poly-N-acetyllactosamine chains, whereas the Manα1-3 arm may carry predominantly branched poly-N-acetyllactosamine chains. 27189951 2 56 located found 476:480 arg1 genome 499:504 the T. brucei genome 485:504 the T. brucei genome 485:504 Despite the presence of complex N-glycans in this organism, no homologues of the canonical N-acetylglucosaminyltransferase I or II genes can be found in the T. brucei genome. 27189951 2 56 located found 476:480 arg2 homologues 395:404 no homologues 392:404 no homologues of the canonical N-acetylglucosaminyltransferase I or II genes 392:467 Despite the presence of complex N-glycans in this organism, no homologues of the canonical N-acetylglucosaminyltransferase I or II genes can be found in the T. brucei genome. 27189951 10 57 theme glycosidic 1991:2000 arg1 linkages 2002:2009 β1-2 glycosidic linkages 1986:2009 β1-2 glycosidic linkages 1986:2009 These results provide further detail on the structure and biosynthesis of complex N-glycans in an important human pathogen and provide a second example of the adaptation by trypanosomes of β3-glycosyltransferase family members to catalyze β1-2 glycosidic linkages. 27189951 3 58 theme trimannosyl-N-acetylchitobiosyl 635:665 arg1 core 667:670 the conserved trimannosyl-N-acetylchitobiosyl core 621:670 the conserved trimannosyl-N-acetylchitobiosyl core of N-linked glycans 621:690 These genes encode the activities that initiate the elaboration of the Manα1-3 and Manα1-6 arms, respectively, of the conserved trimannosyl-N-acetylchitobiosyl core of N-linked glycans. 27189951 1 59 theme N-linked 231:238 arg1 structures 320:329 some exceptionally large poly-N-acetyllactosamine-containing structures 259:329 some exceptionally large poly-N-acetyllactosamine-containing structures 259:329 The bloodstream form of the human pathogen Trypanosoma brucei expresses oligomannose, paucimannose, and complex N-linked glycans, including some exceptionally large poly-N-acetyllactosamine-containing structures. 27189951 1 59 theme N-linked 231:238 arg1 glycans 240:246 complex N-linked glycans 223:246 complex N-linked glycans 223:246 The bloodstream form of the human pathogen Trypanosoma brucei expresses oligomannose, paucimannose, and complex N-linked glycans, including some exceptionally large poly-N-acetyllactosamine-containing structures. 27189951 2 60 attach presence 344:351 arg2 N-glycans 364:372 complex N-glycans 356:372 complex N-glycans 356:372 Despite the presence of complex N-glycans in this organism, no homologues of the canonical N-acetylglucosaminyltransferase I or II genes can be found in the T. brucei genome. 27189951 2 60 attach presence 344:351 arg1 organism 382:389 this organism 377:389 this organism 377:389 Despite the presence of complex N-glycans in this organism, no homologues of the canonical N-acetylglucosaminyltransferase I or II genes can be found in the T. brucei genome. 27189951 0 61 from Function 87:94 arg1 brucei 111:116 Trypanosoma brucei 99:116 Trypanosoma brucei 99:116 A Gene of the β3-Glycosyltransferase Family Encodes N-Acetylglucosaminyltransferase II Function in Trypanosoma brucei. 27189951 10 62 theme N-glycans 1829:1837 arg1 biosynthesis 1805:1816 biosynthesis 1805:1816 biosynthesis 1805:1816 These results provide further detail on the structure and biosynthesis of complex N-glycans in an important human pathogen and provide a second example of the adaptation by trypanosomes of β3-glycosyltransferase family members to catalyze β1-2 glycosidic linkages. 27189951 10 62 theme N-glycans 1829:1837 arg1 structure 1791:1799 structure 1791:1799 structure 1791:1799 These results provide further detail on the structure and biosynthesis of complex N-glycans in an important human pathogen and provide a second example of the adaptation by trypanosomes of β3-glycosyltransferase family members to catalyze β1-2 glycosidic linkages. 27189951 4 63 dep T. 815:816 arg1 brucei 818:823 brucei 818:823 brucei 818:823 Previously, we identified a highly divergent T. brucei N-acetylglucosaminyltransferase I (TbGnTI) among a set of putative T. brucei glycosyltransferase genes belonging to the β3-glycosyltransferase superfamily (Damerow, M., Rodrigues, J. A., Wu, D., Güther, M. L., Mehlert, A., and Ferguson, M. A. (2014) J. Biol. 27189951 10 64 dep structure 1791:1799 arg1 the 1787:1789 the 1787:1789 the 1787:1789 These results provide further detail on the structure and biosynthesis of complex N-glycans in an important human pathogen and provide a second example of the adaptation by trypanosomes of β3-glycosyltransferase family members to catalyze β1-2 glycosidic linkages. 27189951 3 65 theme glycans 684:690 arg1 core 667:670 the conserved trimannosyl-N-acetylchitobiosyl core 621:670 the conserved trimannosyl-N-acetylchitobiosyl core of N-linked glycans 621:690 These genes encode the activities that initiate the elaboration of the Manα1-3 and Manα1-6 arms, respectively, of the conserved trimannosyl-N-acetylchitobiosyl core of N-linked glycans. 27189951 9 66 theme linkage 1487:1493 arg1 analysis 1495:1502 methylation linkage analysis 1475:1502 methylation linkage analysis 1475:1502 Characterization of the large poly-N-acetyllactosamine containing N-glycans of the TbGnTII null mutants by methylation linkage analysis suggests that, in wild-type parasites, the Manα1-6 arm of the conserved trimannosyl core may carry predominantly linear poly-N-acetyllactosamine chains, whereas the Manα1-3 arm may carry predominantly branched poly-N-acetyllactosamine chains. 27189951 8 67 theme brucei 1308:1313 arg1 mutants 1294:1300 TbGnTII null mutants 1281:1300 TbGnTII null mutants of T. brucei 1281:1313 In contrast to multicellular organisms, where GnTII activity is essential, TbGnTII null mutants of T. brucei grow in culture and are still infectious to animals. 27189951 10 68 theme human 1855:1859 arg1 pathogen 1861:1868 an important human pathogen 1842:1868 an important human pathogen 1842:1868 These results provide further detail on the structure and biosynthesis of complex N-glycans in an important human pathogen and provide a second example of the adaptation by trypanosomes of β3-glycosyltransferase family members to catalyze β1-2 glycosidic linkages. 27189951 1 69 theme pathogen 153:160 arg1 brucei 174:179 the human pathogen Trypanosoma brucei 143:179 the human pathogen Trypanosoma brucei 143:179 The bloodstream form of the human pathogen Trypanosoma brucei expresses oligomannose, paucimannose, and complex N-linked glycans, including some exceptionally large poly-N-acetyllactosamine-containing structures. 27189951 2 70 from presence 344:351 arg1 organism 382:389 this organism 377:389 this organism 377:389 Despite the presence of complex N-glycans in this organism, no homologues of the canonical N-acetylglucosaminyltransferase I or II genes can be found in the T. brucei genome. 27189951 8 71 theme TbGnTII 1281:1287 arg1 mutants 1294:1300 TbGnTII null mutants 1281:1300 TbGnTII null mutants of T. brucei 1281:1313 In contrast to multicellular organisms, where GnTII activity is essential, TbGnTII null mutants of T. brucei grow in culture and are still infectious to animals. 27189951 0 72 theme Trypanosoma 99:109 arg1 brucei 111:116 Trypanosoma brucei 99:116 Trypanosoma brucei 99:116 A Gene of the β3-Glycosyltransferase Family Encodes N-Acetylglucosaminyltransferase II Function in Trypanosoma brucei. 27189951 1 73 theme brucei 174:179 arg1 form 135:138 The bloodstream form 119:138 The bloodstream form of the human pathogen Trypanosoma brucei 119:179 The bloodstream form of the human pathogen Trypanosoma brucei expresses oligomannose, paucimannose, and complex N-linked glycans, including some exceptionally large poly-N-acetyllactosamine-containing structures. 27189951 9 74 theme wild-type 1522:1530 arg1 parasites 1532:1540 wild-type parasites 1522:1540 wild-type parasites 1522:1540 Characterization of the large poly-N-acetyllactosamine containing N-glycans of the TbGnTII null mutants by methylation linkage analysis suggests that, in wild-type parasites, the Manα1-6 arm of the conserved trimannosyl core may carry predominantly linear poly-N-acetyllactosamine chains, whereas the Manα1-3 arm may carry predominantly branched poly-N-acetyllactosamine chains. 27189951 4 75 dep L. 954:955 arg1 Biol 1001:1004 Biol 1001:1004 Biol 1001:1004 Previously, we identified a highly divergent T. brucei N-acetylglucosaminyltransferase I (TbGnTI) among a set of putative T. brucei glycosyltransferase genes belonging to the β3-glycosyltransferase superfamily (Damerow, M., Rodrigues, J. A., Wu, D., Güther, M. L., Mehlert, A., and Ferguson, M. A. (2014) J. Biol. 27189951 2 76 dep T. 489:490 arg1 brucei 492:497 brucei 492:497 brucei 492:497 Despite the presence of complex N-glycans in this organism, no homologues of the canonical N-acetylglucosaminyltransferase I or II genes can be found in the T. brucei genome. 27189951 1 77 theme complex 223:229 arg1 structures 320:329 some exceptionally large poly-N-acetyllactosamine-containing structures 259:329 some exceptionally large poly-N-acetyllactosamine-containing structures 259:329 The bloodstream form of the human pathogen Trypanosoma brucei expresses oligomannose, paucimannose, and complex N-linked glycans, including some exceptionally large poly-N-acetyllactosamine-containing structures. 27189951 1 77 theme complex 223:229 arg1 glycans 240:246 complex N-linked glycans 223:246 complex N-linked glycans 223:246 The bloodstream form of the human pathogen Trypanosoma brucei expresses oligomannose, paucimannose, and complex N-linked glycans, including some exceptionally large poly-N-acetyllactosamine-containing structures. 27189951 4 78 theme genes 845:849 arg1 set 799:801 a set 797:801 a set of putative T. brucei glycosyltransferase genes belonging to the β3-glycosyltransferase superfamily (Damerow, M., Rodrigues, J. A., Wu, D., Güther, M. L., Mehlert, A., and Ferguson, M. A. (2014) J. Biol 797:1004 Previously, we identified a highly divergent T. brucei N-acetylglucosaminyltransferase I (TbGnTI) among a set of putative T. brucei glycosyltransferase genes belonging to the β3-glycosyltransferase superfamily (Damerow, M., Rodrigues, J. A., Wu, D., Güther, M. L., Mehlert, A., and Ferguson, M. A. (2014) J. Biol. 27189951 4 78 theme genes 845:849 arg1 genes 845:849 putative T. brucei glycosyltransferase genes 806:849 putative T. brucei glycosyltransferase genes belonging to the β3-glycosyltransferase superfamily (Damerow, M., Rodrigues, J. A., Wu, D., Güther, M. L., Mehlert, A., and Ferguson, M. A. (2014) J. Biol 806:1004 Previously, we identified a highly divergent T. brucei N-acetylglucosaminyltransferase I (TbGnTI) among a set of putative T. brucei glycosyltransferase genes belonging to the β3-glycosyltransferase superfamily (Damerow, M., Rodrigues, J. A., Wu, D., Güther, M. L., Mehlert, A., and Ferguson, M. A. (2014) J. Biol. 27189951 2 79 theme II 460:461 arg1 genes 463:467 the canonical N-acetylglucosaminyltransferase I or II genes 409:467 the canonical N-acetylglucosaminyltransferase I or II genes 409:467 Despite the presence of complex N-glycans in this organism, no homologues of the canonical N-acetylglucosaminyltransferase I or II genes can be found in the T. brucei genome. 27189951 9 80 theme Manα1-6 1547:1553 arg1 core 1588:1591 the conserved trimannosyl core 1562:1591 the conserved trimannosyl core 1562:1591 Characterization of the large poly-N-acetyllactosamine containing N-glycans of the TbGnTII null mutants by methylation linkage analysis suggests that, in wild-type parasites, the Manα1-6 arm of the conserved trimannosyl core may carry predominantly linear poly-N-acetyllactosamine chains, whereas the Manα1-3 arm may carry predominantly branched poly-N-acetyllactosamine chains. 27189951 9 80 theme Manα1-6 1547:1553 arg1 arm 1555:1557 the Manα1-6 arm 1543:1557 the Manα1-6 arm of the conserved trimannosyl core 1543:1591 Characterization of the large poly-N-acetyllactosamine containing N-glycans of the TbGnTII null mutants by methylation linkage analysis suggests that, in wild-type parasites, the Manα1-6 arm of the conserved trimannosyl core may carry predominantly linear poly-N-acetyllactosamine chains, whereas the Manα1-3 arm may carry predominantly branched poly-N-acetyllactosamine chains. 27189951 3 81 link N-linked 675:682 arg1 glycans 684:690 N-linked glycans 675:690 N-linked glycans 675:690 These genes encode the activities that initiate the elaboration of the Manα1-3 and Manα1-6 arms, respectively, of the conserved trimannosyl-N-acetylchitobiosyl core of N-linked glycans. 27189951 2 82 theme I 455:455 arg1 genes 463:467 the canonical N-acetylglucosaminyltransferase I or II genes 409:467 the canonical N-acetylglucosaminyltransferase I or II genes 409:467 Despite the presence of complex N-glycans in this organism, no homologues of the canonical N-acetylglucosaminyltransferase I or II genes can be found in the T. brucei genome. 27189951 4 83 theme putative 806:813 arg1 genes 845:849 putative T. brucei glycosyltransferase genes 806:849 putative T. brucei glycosyltransferase genes belonging to the β3-glycosyltransferase superfamily (Damerow, M., Rodrigues, J. A., Wu, D., Güther, M. L., Mehlert, A., and Ferguson, M. A. (2014) J. Biol 806:1004 Previously, we identified a highly divergent T. brucei N-acetylglucosaminyltransferase I (TbGnTI) among a set of putative T. brucei glycosyltransferase genes belonging to the β3-glycosyltransferase superfamily (Damerow, M., Rodrigues, J. A., Wu, D., Güther, M. L., Mehlert, A., and Ferguson, M. A. (2014) J. Biol. 27189951 7 84 theme β3-glycosyltransferase 1091:1112 arg1 family 1114:1119 the same β3-glycosyltransferase family 1082:1119 the same β3-glycosyltransferase family 1082:1119 Here, we demonstrate that TbGT15, another member of the same β3-glycosyltransferase family, encodes an equally divergent N-acetylglucosaminyltransferase II (TbGnTII) activity. 27189951 8 85 theme GnTII 1252:1256 arg1 activity 1258:1265 GnTII activity 1252:1265 GnTII activity 1252:1265 In contrast to multicellular organisms, where GnTII activity is essential, TbGnTII null mutants of T. brucei grow in culture and are still infectious to animals. 27189951 9 86 theme conserved 1566:1574 arg1 core 1588:1591 the conserved trimannosyl core 1562:1591 the conserved trimannosyl core 1562:1591 Characterization of the large poly-N-acetyllactosamine containing N-glycans of the TbGnTII null mutants by methylation linkage analysis suggests that, in wild-type parasites, the Manα1-6 arm of the conserved trimannosyl core may carry predominantly linear poly-N-acetyllactosamine chains, whereas the Manα1-3 arm may carry predominantly branched poly-N-acetyllactosamine chains. 27189951 0 87 theme N-Acetylglucosaminyltransferase 52:82 arg1 Function 87:94 N-Acetylglucosaminyltransferase II Function 52:94 N-Acetylglucosaminyltransferase II Function in Trypanosoma brucei 52:116 A Gene of the β3-Glycosyltransferase Family Encodes N-Acetylglucosaminyltransferase II Function in Trypanosoma brucei. 27189951 0 87 theme N-Acetylglucosaminyltransferase 52:82 arg1 Gene 2:5 A Gene 0:5 A Gene of the β3-Glycosyltransferase Family 0:42 A Gene of the β3-Glycosyltransferase Family Encodes N-Acetylglucosaminyltransferase II Function in Trypanosoma brucei. 27189951 9 88 theme core 1588:1591 arg1 core 1588:1591 the conserved trimannosyl core 1562:1591 the conserved trimannosyl core 1562:1591 Characterization of the large poly-N-acetyllactosamine containing N-glycans of the TbGnTII null mutants by methylation linkage analysis suggests that, in wild-type parasites, the Manα1-6 arm of the conserved trimannosyl core may carry predominantly linear poly-N-acetyllactosamine chains, whereas the Manα1-3 arm may carry predominantly branched poly-N-acetyllactosamine chains. 27189951 9 88 theme core 1588:1591 arg1 arm 1555:1557 the Manα1-6 arm 1543:1557 the Manα1-6 arm of the conserved trimannosyl core 1543:1591 Characterization of the large poly-N-acetyllactosamine containing N-glycans of the TbGnTII null mutants by methylation linkage analysis suggests that, in wild-type parasites, the Manα1-6 arm of the conserved trimannosyl core may carry predominantly linear poly-N-acetyllactosamine chains, whereas the Manα1-3 arm may carry predominantly branched poly-N-acetyllactosamine chains. 27189951 4 89 dep superfamily 891:901 arg1 2014 992:995 2014 992:995 2014 992:995 Previously, we identified a highly divergent T. brucei N-acetylglucosaminyltransferase I (TbGnTI) among a set of putative T. brucei glycosyltransferase genes belonging to the β3-glycosyltransferase superfamily (Damerow, M., Rodrigues, J. A., Wu, D., Güther, M. L., Mehlert, A., and Ferguson, M. A. (2014) J. Biol. 27189951 4 89 dep superfamily 891:901 arg1 L. 954:955 L. 954:955 L. 954:955 Previously, we identified a highly divergent T. brucei N-acetylglucosaminyltransferase I (TbGnTI) among a set of putative T. brucei glycosyltransferase genes belonging to the β3-glycosyltransferase superfamily (Damerow, M., Rodrigues, J. A., Wu, D., Güther, M. L., Mehlert, A., and Ferguson, M. A. (2014) J. Biol. 27189951 4 89 dep superfamily 891:901 arg1 Rodrigues 917:925 Rodrigues 917:925 Rodrigues 917:925 Previously, we identified a highly divergent T. brucei N-acetylglucosaminyltransferase I (TbGnTI) among a set of putative T. brucei glycosyltransferase genes belonging to the β3-glycosyltransferase superfamily (Damerow, M., Rodrigues, J. A., Wu, D., Güther, M. L., Mehlert, A., and Ferguson, M. A. (2014) J. Biol. 27189951 4 89 dep superfamily 891:901 arg1 D. 939:940 D. 939:940 D. 939:940 Previously, we identified a highly divergent T. brucei N-acetylglucosaminyltransferase I (TbGnTI) among a set of putative T. brucei glycosyltransferase genes belonging to the β3-glycosyltransferase superfamily (Damerow, M., Rodrigues, J. A., Wu, D., Güther, M. L., Mehlert, A., and Ferguson, M. A. (2014) J. Biol. 27189951 4 89 dep superfamily 891:901 arg1 J. 928:929 J. 928:929 J. 928:929 Previously, we identified a highly divergent T. brucei N-acetylglucosaminyltransferase I (TbGnTI) among a set of putative T. brucei glycosyltransferase genes belonging to the β3-glycosyltransferase superfamily (Damerow, M., Rodrigues, J. A., Wu, D., Güther, M. L., Mehlert, A., and Ferguson, M. A. (2014) J. Biol. 27189951 4 89 dep superfamily 891:901 arg1 M. 985:986 M. 985:986 M. 985:986 Previously, we identified a highly divergent T. brucei N-acetylglucosaminyltransferase I (TbGnTI) among a set of putative T. brucei glycosyltransferase genes belonging to the β3-glycosyltransferase superfamily (Damerow, M., Rodrigues, J. A., Wu, D., Güther, M. L., Mehlert, A., and Ferguson, M. A. (2014) J. Biol. 27189951 4 89 dep superfamily 891:901 arg1 A 988:988 A 988:988 A 988:988 Previously, we identified a highly divergent T. brucei N-acetylglucosaminyltransferase I (TbGnTI) among a set of putative T. brucei glycosyltransferase genes belonging to the β3-glycosyltransferase superfamily (Damerow, M., Rodrigues, J. A., Wu, D., Güther, M. L., Mehlert, A., and Ferguson, M. A. (2014) J. Biol. 27189951 4 89 dep superfamily 891:901 arg1 Güther 943:948 Güther 943:948 Güther 943:948 Previously, we identified a highly divergent T. brucei N-acetylglucosaminyltransferase I (TbGnTI) among a set of putative T. brucei glycosyltransferase genes belonging to the β3-glycosyltransferase superfamily (Damerow, M., Rodrigues, J. A., Wu, D., Güther, M. L., Mehlert, A., and Ferguson, M. A. (2014) J. Biol. 27189951 4 89 dep superfamily 891:901 arg1 A. 967:968 A. 967:968 A. 967:968 Previously, we identified a highly divergent T. brucei N-acetylglucosaminyltransferase I (TbGnTI) among a set of putative T. brucei glycosyltransferase genes belonging to the β3-glycosyltransferase superfamily (Damerow, M., Rodrigues, J. A., Wu, D., Güther, M. L., Mehlert, A., and Ferguson, M. A. (2014) J. Biol. 27189951 4 89 dep superfamily 891:901 arg1 M. 913:914 M. 913:914 M. 913:914 Previously, we identified a highly divergent T. brucei N-acetylglucosaminyltransferase I (TbGnTI) among a set of putative T. brucei glycosyltransferase genes belonging to the β3-glycosyltransferase superfamily (Damerow, M., Rodrigues, J. A., Wu, D., Güther, M. L., Mehlert, A., and Ferguson, M. A. (2014) J. Biol. 27189951 4 89 dep superfamily 891:901 arg1 Wu 935:936 Wu 935:936 Wu 935:936 Previously, we identified a highly divergent T. brucei N-acetylglucosaminyltransferase I (TbGnTI) among a set of putative T. brucei glycosyltransferase genes belonging to the β3-glycosyltransferase superfamily (Damerow, M., Rodrigues, J. A., Wu, D., Güther, M. L., Mehlert, A., and Ferguson, M. A. (2014) J. Biol. 27189951 4 89 dep superfamily 891:901 arg1 M. 951:952 M. 951:952 M. 951:952 Previously, we identified a highly divergent T. brucei N-acetylglucosaminyltransferase I (TbGnTI) among a set of putative T. brucei glycosyltransferase genes belonging to the β3-glycosyltransferase superfamily (Damerow, M., Rodrigues, J. A., Wu, D., Güther, M. L., Mehlert, A., and Ferguson, M. A. (2014) J. Biol. 27189951 4 90 dep T. 738:739 arg1 brucei 741:746 brucei 741:746 brucei 741:746 Previously, we identified a highly divergent T. brucei N-acetylglucosaminyltransferase I (TbGnTI) among a set of putative T. brucei glycosyltransferase genes belonging to the β3-glycosyltransferase superfamily (Damerow, M., Rodrigues, J. A., Wu, D., Güther, M. L., Mehlert, A., and Ferguson, M. A. (2014) J. Biol. 27189951 9 91 theme linear 1617:1622 arg1 chains 1649:1654 predominantly linear poly-N-acetyllactosamine chains 1603:1654 predominantly linear poly-N-acetyllactosamine chains 1603:1654 Characterization of the large poly-N-acetyllactosamine containing N-glycans of the TbGnTII null mutants by methylation linkage analysis suggests that, in wild-type parasites, the Manα1-6 arm of the conserved trimannosyl core may carry predominantly linear poly-N-acetyllactosamine chains, whereas the Manα1-3 arm may carry predominantly branched poly-N-acetyllactosamine chains. 27189951 10 92 theme family 1959:1964 arg1 members 1966:1972 β3-glycosyltransferase family members 1936:1972 β3-glycosyltransferase family members 1936:1972 These results provide further detail on the structure and biosynthesis of complex N-glycans in an important human pathogen and provide a second example of the adaptation by trypanosomes of β3-glycosyltransferase family members to catalyze β1-2 glycosidic linkages. 27189951 4 93 theme β3-glycosyltransferase 868:889 arg1 superfamily 891:901 the β3-glycosyltransferase superfamily 864:901 the β3-glycosyltransferase superfamily (Damerow, M., Rodrigues, J. A., Wu, D., Güther, M. L., Mehlert, A., and Ferguson, M. A. (2014) J. Biol 864:1004 Previously, we identified a highly divergent T. brucei N-acetylglucosaminyltransferase I (TbGnTI) among a set of putative T. brucei glycosyltransferase genes belonging to the β3-glycosyltransferase superfamily (Damerow, M., Rodrigues, J. A., Wu, D., Güther, M. L., Mehlert, A., and Ferguson, M. A. (2014) J. Biol. 27189951 2 94 theme canonical 413:421 arg1 genes 463:467 the canonical N-acetylglucosaminyltransferase I or II genes 409:467 the canonical N-acetylglucosaminyltransferase I or II genes 409:467 Despite the presence of complex N-glycans in this organism, no homologues of the canonical N-acetylglucosaminyltransferase I or II genes can be found in the T. brucei genome. 27885610 3 0 theme preferred 540:548 arg1 methodology 550:560 the preferred methodology 536:560 the preferred methodology for the study of C. jejuni glycosylation 536:601 In general, mass spectrometry-based characterization has become the preferred methodology for the study of C. jejuni glycosylation because of its speed, sensitivity, and ability to enable both qualitative and quantitative assessments of glycosylation events. 27885610 4 1 theme mass 848:851 arg1 spectrometry 853:864 mass spectrometry 848:864 mass spectrometry (MS) instrumentation 848:885 In these experiments the generation of insightful data requires the careful selection of experimental approaches and mass spectrometry (MS) instrumentation. 27885610 4 1 theme mass 848:851 arg1 MS 867:868 MS 867:868 MS 867:868 In these experiments the generation of insightful data requires the careful selection of experimental approaches and mass spectrometry (MS) instrumentation. 27885610 5 2 contain have 916:919 arg1 it 897:898 it 897:898 it 897:898 As such, it is essential to have a deep understanding of the technologies and approaches used for characterization of glycosylation events. 27885610 5 2 contain have 916:919 arg2 understanding 928:940 a deep understanding 921:940 a deep understanding of the technologies and approaches used for characterization of glycosylation events 921:1025 As such, it is essential to have a deep understanding of the technologies and approaches used for characterization of glycosylation events. 27885610 3 3 theme C. 579:580 arg1 glycosylation 589:601 C. jejuni glycosylation 579:601 C. jejuni glycosylation 579:601 In general, mass spectrometry-based characterization has become the preferred methodology for the study of C. jejuni glycosylation because of its speed, sensitivity, and ability to enable both qualitative and quantitative assessments of glycosylation events. 27885610 6 4 theme jejuni 1094:1099 arg1 glycoproteins 1101:1113 C. jejuni glycoproteins 1091:1113 C. jejuni glycoproteins using protein-/peptide-centric approaches 1091:1155 Here we describe protocols for the initial characterization of C. jejuni glycoproteins using protein-/peptide-centric approaches and discuss considerations that can enhance the generation of insightful data. 27885610 3 5 theme jejuni 582:587 arg1 glycosylation 589:601 C. jejuni glycosylation 579:601 C. jejuni glycosylation 579:601 In general, mass spectrometry-based characterization has become the preferred methodology for the study of C. jejuni glycosylation because of its speed, sensitivity, and ability to enable both qualitative and quantitative assessments of glycosylation events. 27885610 2 6 theme systems 296:302 arg1 discovery 256:264 discovery 256:264 discovery 256:264 The discovery and characterization of these systems both have revealed important biological insight into C. jejuni and have led to the refinement and enhancement of methodologies to characterize bacterial glycosylation. 27885610 2 6 theme systems 296:302 arg1 characterization 270:285 characterization 270:285 characterization 270:285 The discovery and characterization of these systems both have revealed important biological insight into C. jejuni and have led to the refinement and enhancement of methodologies to characterize bacterial glycosylation. 27885610 1 7 theme C. 126:127 arg1 jejuni 118:123 Campylobacter jejuni 104:123 Campylobacter jejuni (C. jejuni) 104:135 The glycosylation systems of Campylobacter jejuni (C. jejuni) are considered archetypal examples of both N- and O-linked glycosylations in the field of bacterial glycosylation. 27885610 1 7 theme C. 126:127 arg1 jejuni 129:134 C. jejuni 126:134 C. jejuni 126:134 The glycosylation systems of Campylobacter jejuni (C. jejuni) are considered archetypal examples of both N- and O-linked glycosylations in the field of bacterial glycosylation. 27885610 6 8 theme glycoproteins 1101:1113 arg1 characterization 1071:1086 the initial characterization 1059:1086 the initial characterization of C. jejuni glycoproteins using protein-/peptide-centric approaches 1059:1155 Here we describe protocols for the initial characterization of C. jejuni glycoproteins using protein-/peptide-centric approaches and discuss considerations that can enhance the generation of insightful data. 27885610 1 9 theme glycosylation 79:91 arg1 systems 93:99 The glycosylation systems 75:99 The glycosylation systems of Campylobacter jejuni (C. jejuni) 75:135 The glycosylation systems of Campylobacter jejuni (C. jejuni) are considered archetypal examples of both N- and O-linked glycosylations in the field of bacterial glycosylation. 27885610 2 10 dep discovery 256:264 arg1 The 252:254 The 252:254 The 252:254 The discovery and characterization of these systems both have revealed important biological insight into C. jejuni and have led to the refinement and enhancement of methodologies to characterize bacterial glycosylation. 27885610 1 11 link O-linked 187:194 arg1 glycosylations 196:209 O-linked glycosylations 187:209 O-linked glycosylations 187:209 The glycosylation systems of Campylobacter jejuni (C. jejuni) are considered archetypal examples of both N- and O-linked glycosylations in the field of bacterial glycosylation. 27885610 4 12 theme experimental 820:831 arg1 approaches 833:842 experimental approaches 820:842 experimental approaches 820:842 In these experiments the generation of insightful data requires the careful selection of experimental approaches and mass spectrometry (MS) instrumentation. 27885610 1 13 theme N- 180:181 arg1 examples 163:170 archetypal examples 152:170 archetypal examples of both N- and O-linked glycosylations 152:209 The glycosylation systems of Campylobacter jejuni (C. jejuni) are considered archetypal examples of both N- and O-linked glycosylations in the field of bacterial glycosylation. 27885610 0 14 from Spectrometry 37:48 arg1 jejuni 67:72 Campylobacter jejuni 53:72 Campylobacter jejuni 53:72 Characterizing Glycoproteins by Mass Spectrometry in Campylobacter jejuni. 27885610 2 15 theme important 323:331 arg1 insight 344:350 important biological insight 323:350 important biological insight into C. jejuni 323:365 The discovery and characterization of these systems both have revealed important biological insight into C. jejuni and have led to the refinement and enhancement of methodologies to characterize bacterial glycosylation. 27885610 2 16 theme biological 333:342 arg1 insight 344:350 important biological insight 323:350 important biological insight into C. jejuni 323:365 The discovery and characterization of these systems both have revealed important biological insight into C. jejuni and have led to the refinement and enhancement of methodologies to characterize bacterial glycosylation. 27885610 1 17 theme Campylobacter 104:116 arg1 jejuni 118:123 Campylobacter jejuni 104:123 Campylobacter jejuni (C. jejuni) 104:135 The glycosylation systems of Campylobacter jejuni (C. jejuni) are considered archetypal examples of both N- and O-linked glycosylations in the field of bacterial glycosylation. 27885610 1 17 theme Campylobacter 104:116 arg1 jejuni 129:134 C. jejuni 126:134 C. jejuni 126:134 The glycosylation systems of Campylobacter jejuni (C. jejuni) are considered archetypal examples of both N- and O-linked glycosylations in the field of bacterial glycosylation. 27885610 1 18 theme O-linked 187:194 arg1 glycosylations 196:209 O-linked glycosylations 187:209 O-linked glycosylations 187:209 The glycosylation systems of Campylobacter jejuni (C. jejuni) are considered archetypal examples of both N- and O-linked glycosylations in the field of bacterial glycosylation. 27885610 0 19 theme Mass 32:35 arg1 Spectrometry 37:48 Mass Spectrometry 32:48 Mass Spectrometry in Campylobacter jejuni 32:72 Characterizing Glycoproteins by Mass Spectrometry in Campylobacter jejuni. 27885610 4 20 theme data 781:784 arg1 generation 756:765 the generation 752:765 the generation of insightful data 752:784 In these experiments the generation of insightful data requires the careful selection of experimental approaches and mass spectrometry (MS) instrumentation. 27885610 6 21 gly glycoproteins 1101:1113 arg1 glycoproteins 1101:1113 C. jejuni glycoproteins 1091:1113 C. jejuni glycoproteins using protein-/peptide-centric approaches 1091:1155 Here we describe protocols for the initial characterization of C. jejuni glycoproteins using protein-/peptide-centric approaches and discuss considerations that can enhance the generation of insightful data. 27885610 1 22 theme jejuni 118:123 arg1 systems 93:99 The glycosylation systems 75:99 The glycosylation systems of Campylobacter jejuni (C. jejuni) 75:135 The glycosylation systems of Campylobacter jejuni (C. jejuni) are considered archetypal examples of both N- and O-linked glycosylations in the field of bacterial glycosylation. 27885610 1 23 theme glycosylations 196:209 arg1 examples 163:170 archetypal examples 152:170 archetypal examples of both N- and O-linked glycosylations 152:209 The glycosylation systems of Campylobacter jejuni (C. jejuni) are considered archetypal examples of both N- and O-linked glycosylations in the field of bacterial glycosylation. 27885610 2 24 theme bacterial 447:455 arg1 glycosylation 457:469 bacterial glycosylation 447:469 bacterial glycosylation 447:469 The discovery and characterization of these systems both have revealed important biological insight into C. jejuni and have led to the refinement and enhancement of methodologies to characterize bacterial glycosylation. 27885610 4 25 theme approaches 833:842 arg1 selection 807:815 the careful selection 795:815 the careful selection of experimental approaches and mass spectrometry (MS) instrumentation 795:885 In these experiments the generation of insightful data requires the careful selection of experimental approaches and mass spectrometry (MS) instrumentation. 27885610 6 26 theme data 1230:1233 arg1 generation 1205:1214 the generation 1201:1214 the generation of insightful data 1201:1233 Here we describe protocols for the initial characterization of C. jejuni glycoproteins using protein-/peptide-centric approaches and discuss considerations that can enhance the generation of insightful data. 27885610 3 27 theme spectrometry-based 489:506 arg1 characterization 508:523 mass spectrometry-based characterization 484:523 mass spectrometry-based characterization 484:523 In general, mass spectrometry-based characterization has become the preferred methodology for the study of C. jejuni glycosylation because of its speed, sensitivity, and ability to enable both qualitative and quantitative assessments of glycosylation events. 27885610 5 28 theme technologies 949:960 arg1 understanding 928:940 a deep understanding 921:940 a deep understanding of the technologies and approaches used for characterization of glycosylation events 921:1025 As such, it is essential to have a deep understanding of the technologies and approaches used for characterization of glycosylation events. 27885610 3 29 theme quantitative 681:692 arg1 assessments 694:704 both qualitative and quantitative assessments 660:704 both qualitative and quantitative assessments of glycosylation events 660:728 In general, mass spectrometry-based characterization has become the preferred methodology for the study of C. jejuni glycosylation because of its speed, sensitivity, and ability to enable both qualitative and quantitative assessments of glycosylation events. 27885610 6 30 theme protein-/peptide-centric 1121:1144 arg1 approaches 1146:1155 protein-/peptide-centric approaches 1121:1155 protein-/peptide-centric approaches 1121:1155 Here we describe protocols for the initial characterization of C. jejuni glycoproteins using protein-/peptide-centric approaches and discuss considerations that can enhance the generation of insightful data. 27885610 2 31 theme methodologies 417:429 arg1 enhancement 402:412 enhancement 402:412 enhancement 402:412 The discovery and characterization of these systems both have revealed important biological insight into C. jejuni and have led to the refinement and enhancement of methodologies to characterize bacterial glycosylation. 27885610 2 31 theme methodologies 417:429 arg1 refinement 387:396 refinement 387:396 refinement 387:396 The discovery and characterization of these systems both have revealed important biological insight into C. jejuni and have led to the refinement and enhancement of methodologies to characterize bacterial glycosylation. 27885610 6 32 theme initial 1063:1069 arg1 characterization 1071:1086 the initial characterization 1059:1086 the initial characterization of C. jejuni glycoproteins using protein-/peptide-centric approaches 1059:1155 Here we describe protocols for the initial characterization of C. jejuni glycoproteins using protein-/peptide-centric approaches and discuss considerations that can enhance the generation of insightful data. 27885610 4 33 theme careful 799:805 arg1 selection 807:815 the careful selection 795:815 the careful selection of experimental approaches and mass spectrometry (MS) instrumentation 795:885 In these experiments the generation of insightful data requires the careful selection of experimental approaches and mass spectrometry (MS) instrumentation. 27885610 3 34 theme qualitative 665:675 arg1 assessments 694:704 both qualitative and quantitative assessments 660:704 both qualitative and quantitative assessments of glycosylation events 660:728 In general, mass spectrometry-based characterization has become the preferred methodology for the study of C. jejuni glycosylation because of its speed, sensitivity, and ability to enable both qualitative and quantitative assessments of glycosylation events. 27885610 5 35 theme events 1020:1025 arg1 characterization 986:1001 characterization 986:1001 characterization of glycosylation events 986:1025 As such, it is essential to have a deep understanding of the technologies and approaches used for characterization of glycosylation events. 27885610 2 36 dep revealed 314:321 arg1 both 304:307 both 304:307 both 304:307 The discovery and characterization of these systems both have revealed important biological insight into C. jejuni and have led to the refinement and enhancement of methodologies to characterize bacterial glycosylation. 27885610 0 37 theme Campylobacter 53:65 arg1 jejuni 67:72 Campylobacter jejuni 53:72 Campylobacter jejuni 53:72 Characterizing Glycoproteins by Mass Spectrometry in Campylobacter jejuni. 27885610 3 38 theme glycosylation 709:721 arg1 events 723:728 glycosylation events 709:728 glycosylation events 709:728 In general, mass spectrometry-based characterization has become the preferred methodology for the study of C. jejuni glycosylation because of its speed, sensitivity, and ability to enable both qualitative and quantitative assessments of glycosylation events. 27885610 4 39 theme instrumentation 871:885 arg1 selection 807:815 the careful selection 795:815 the careful selection of experimental approaches and mass spectrometry (MS) instrumentation 795:885 In these experiments the generation of insightful data requires the careful selection of experimental approaches and mass spectrometry (MS) instrumentation. 27885610 2 40 theme C. 357:358 arg1 jejuni 360:365 C. jejuni 357:365 C. jejuni 357:365 The discovery and characterization of these systems both have revealed important biological insight into C. jejuni and have led to the refinement and enhancement of methodologies to characterize bacterial glycosylation. 27885610 3 41 theme events 723:728 arg1 assessments 694:704 both qualitative and quantitative assessments 660:704 both qualitative and quantitative assessments of glycosylation events 660:728 In general, mass spectrometry-based characterization has become the preferred methodology for the study of C. jejuni glycosylation because of its speed, sensitivity, and ability to enable both qualitative and quantitative assessments of glycosylation events. 27885610 2 42 dep refinement 387:396 arg1 the 383:385 the 383:385 the 383:385 The discovery and characterization of these systems both have revealed important biological insight into C. jejuni and have led to the refinement and enhancement of methodologies to characterize bacterial glycosylation. 27885610 4 43 theme insightful 770:779 arg1 data 781:784 insightful data 770:784 insightful data 770:784 In these experiments the generation of insightful data requires the careful selection of experimental approaches and mass spectrometry (MS) instrumentation. 27885610 3 44 theme glycosylation 589:601 arg1 study 570:574 the study 566:574 the study of C. jejuni glycosylation 566:601 In general, mass spectrometry-based characterization has become the preferred methodology for the study of C. jejuni glycosylation because of its speed, sensitivity, and ability to enable both qualitative and quantitative assessments of glycosylation events. 27885610 5 45 dep technologies 949:960 arg1 the 945:947 the 945:947 the 945:947 As such, it is essential to have a deep understanding of the technologies and approaches used for characterization of glycosylation events. 27885610 5 46 theme glycosylation 1006:1018 arg1 events 1020:1025 glycosylation events 1006:1025 glycosylation events 1006:1025 As such, it is essential to have a deep understanding of the technologies and approaches used for characterization of glycosylation events. 27885610 5 47 theme approaches 966:975 arg1 understanding 928:940 a deep understanding 921:940 a deep understanding of the technologies and approaches used for characterization of glycosylation events 921:1025 As such, it is essential to have a deep understanding of the technologies and approaches used for characterization of glycosylation events. 27885610 6 48 theme insightful 1219:1228 arg1 data 1230:1233 insightful data 1219:1233 insightful data 1219:1233 Here we describe protocols for the initial characterization of C. jejuni glycoproteins using protein-/peptide-centric approaches and discuss considerations that can enhance the generation of insightful data. 27885610 1 49 theme bacterial 227:235 arg1 glycosylation 237:249 bacterial glycosylation 227:249 bacterial glycosylation 227:249 The glycosylation systems of Campylobacter jejuni (C. jejuni) are considered archetypal examples of both N- and O-linked glycosylations in the field of bacterial glycosylation. 27885610 6 50 theme C. 1091:1092 arg1 glycoproteins 1101:1113 C. jejuni glycoproteins 1091:1113 C. jejuni glycoproteins using protein-/peptide-centric approaches 1091:1155 Here we describe protocols for the initial characterization of C. jejuni glycoproteins using protein-/peptide-centric approaches and discuss considerations that can enhance the generation of insightful data. 27885610 3 51 theme mass 484:487 arg1 characterization 508:523 mass spectrometry-based characterization 484:523 mass spectrometry-based characterization 484:523 In general, mass spectrometry-based characterization has become the preferred methodology for the study of C. jejuni glycosylation because of its speed, sensitivity, and ability to enable both qualitative and quantitative assessments of glycosylation events. 27885610 5 52 theme deep 923:926 arg1 understanding 928:940 a deep understanding 921:940 a deep understanding of the technologies and approaches used for characterization of glycosylation events 921:1025 As such, it is essential to have a deep understanding of the technologies and approaches used for characterization of glycosylation events. 27885610 1 53 theme glycosylation 237:249 arg1 field 218:222 the field 214:222 the field of bacterial glycosylation 214:249 The glycosylation systems of Campylobacter jejuni (C. jejuni) are considered archetypal examples of both N- and O-linked glycosylations in the field of bacterial glycosylation. 27885610 4 54 theme spectrometry 853:864 arg1 instrumentation 871:885 mass spectrometry (MS) instrumentation 848:885 mass spectrometry (MS) instrumentation 848:885 In these experiments the generation of insightful data requires the careful selection of experimental approaches and mass spectrometry (MS) instrumentation. 27885610 1 55 theme archetypal 152:161 arg1 examples 163:170 archetypal examples 152:170 archetypal examples of both N- and O-linked glycosylations 152:209 The glycosylation systems of Campylobacter jejuni (C. jejuni) are considered archetypal examples of both N- and O-linked glycosylations in the field of bacterial glycosylation. 26914640 3 0 link α-linked 456:463 arg1 mannopyranose 465:477 an α-linked mannopyranose 453:477 an α-linked mannopyranose 453:477 The D-βhEnd unit also carries an α-linked mannopyranose at the most hindered N of its cyclic guanidine ring. 26914640 1 1 theme antibiotic 146:155 arg1 activity 157:164 potent antibiotic activity 139:164 potent antibiotic activity 139:164 The mannopeptimycins are a class of glycopeptide natural products with unusual structures and potent antibiotic activity against a range of Gram-positive multidrug-resistant bacteria. 26914640 6 2 theme C-H 927:929 arg1 method 941:946 a Pd-catalyzed C-H arylation method 912:946 a Pd-catalyzed C-H arylation method 912:946 The L-βMePhe unit was prepared using a Pd-catalyzed C-H arylation method. 26914640 8 3 theme scaffold 1074:1081 arg1 assembly 1043:1050 A convergent assembly 1030:1050 A convergent assembly of the cyclic peptide scaffold 1030:1081 A convergent assembly of the cyclic peptide scaffold and a single global hydrogenolysis deprotection operation provided mannopeptimycin α and β. 26914640 8 3 theme scaffold 1074:1081 arg1 operation 1131:1139 a single global hydrogenolysis deprotection operation 1087:1139 a single global hydrogenolysis deprotection operation 1087:1139 A convergent assembly of the cyclic peptide scaffold and a single global hydrogenolysis deprotection operation provided mannopeptimycin α and β. 26914640 3 4 theme cyclic 509:514 arg1 ring 526:529 its cyclic guanidine ring 505:529 its cyclic guanidine ring 505:529 The D-βhEnd unit also carries an α-linked mannopyranose at the most hindered N of its cyclic guanidine ring. 26914640 8 5 theme convergent 1032:1041 arg1 assembly 1043:1050 A convergent assembly 1030:1050 A convergent assembly of the cyclic peptide scaffold 1030:1081 A convergent assembly of the cyclic peptide scaffold and a single global hydrogenolysis deprotection operation provided mannopeptimycin α and β. 26914640 2 6 contain carrying 359:366 arg1 D-Tyr 353:357 an O-glycosylated D-Tyr 335:357 an O-glycosylated D-Tyr carrying an α-linked dimannose 335:388 Their cyclic hexapeptide core features a pair of unprecedented β-hydroxyenduracididines (L- and D-βhEnd), an O-glycosylated D-Tyr carrying an α-linked dimannose, and a β-methylated Phe residue. 26914640 2 6 contain carrying 359:366 arg2 dimannose 380:388 an α-linked dimannose 368:388 an α-linked dimannose 368:388 Their cyclic hexapeptide core features a pair of unprecedented β-hydroxyenduracididines (L- and D-βhEnd), an O-glycosylated D-Tyr carrying an α-linked dimannose, and a β-methylated Phe residue. 26914640 2 6 contain carrying 359:366 arg1 β-hydroxyenduracididines 292:315 unprecedented β-hydroxyenduracididines 278:315 unprecedented β-hydroxyenduracididines (L- and D-βhEnd) 278:332 Their cyclic hexapeptide core features a pair of unprecedented β-hydroxyenduracididines (L- and D-βhEnd), an O-glycosylated D-Tyr carrying an α-linked dimannose, and a β-methylated Phe residue. 26914640 3 7 theme guanidine 516:524 arg1 ring 526:529 its cyclic guanidine ring 505:529 its cyclic guanidine ring 505:529 The D-βhEnd unit also carries an α-linked mannopyranose at the most hindered N of its cyclic guanidine ring. 26914640 4 8 theme α 595:595 arg1 synthesis 566:574 the first total synthesis 550:574 the first total synthesis of mannopeptimycin α and β with fully elaborated N- and O-linked sugars 550:646 Herein, we report the first total synthesis of mannopeptimycin α and β with fully elaborated N- and O-linked sugars. 26914640 5 9 theme mannosyl 724:731 arg1 donor 755:759 a mannosyl ortho-alkynylbenzoate donor 722:759 a mannosyl ortho-alkynylbenzoate donor 722:759 Critically, a gold-catalyzed N-glycosylation of a D-βhEnd substrate with a mannosyl ortho-alkynylbenzoate donor enabled the synthesis of the most challenging N-Man-D-βhEnd unit with excellent efficiency and stereoselectivity. 26914640 2 10 link α-linked 371:378 arg1 dimannose 380:388 an α-linked dimannose 368:388 an α-linked dimannose 368:388 Their cyclic hexapeptide core features a pair of unprecedented β-hydroxyenduracididines (L- and D-βhEnd), an O-glycosylated D-Tyr carrying an α-linked dimannose, and a β-methylated Phe residue. 26914640 2 11 theme α-linked 371:378 arg1 dimannose 380:388 an α-linked dimannose 368:388 an α-linked dimannose 368:388 Their cyclic hexapeptide core features a pair of unprecedented β-hydroxyenduracididines (L- and D-βhEnd), an O-glycosylated D-Tyr carrying an α-linked dimannose, and a β-methylated Phe residue. 26914640 3 12 theme hindered 491:498 arg1 N 500:500 the most hindered N 482:500 the most hindered N of its cyclic guanidine ring 482:529 The D-βhEnd unit also carries an α-linked mannopyranose at the most hindered N of its cyclic guanidine ring. 26914640 5 13 theme ortho-alkynylbenzoate 733:753 arg1 donor 755:759 a mannosyl ortho-alkynylbenzoate donor 722:759 a mannosyl ortho-alkynylbenzoate donor 722:759 Critically, a gold-catalyzed N-glycosylation of a D-βhEnd substrate with a mannosyl ortho-alkynylbenzoate donor enabled the synthesis of the most challenging N-Man-D-βhEnd unit with excellent efficiency and stereoselectivity. 26914640 6 14 theme Pd-catalyzed 914:925 arg1 method 941:946 a Pd-catalyzed C-H arylation method 912:946 a Pd-catalyzed C-H arylation method 912:946 The L-βMePhe unit was prepared using a Pd-catalyzed C-H arylation method. 26914640 8 15 theme cyclic 1059:1064 arg1 scaffold 1074:1081 the cyclic peptide scaffold 1055:1081 the cyclic peptide scaffold 1055:1081 A convergent assembly of the cyclic peptide scaffold and a single global hydrogenolysis deprotection operation provided mannopeptimycin α and β. 26914640 4 16 theme elaborated 614:623 arg1 N- 625:626 fully elaborated N- 608:626 fully elaborated N- 608:626 Herein, we report the first total synthesis of mannopeptimycin α and β with fully elaborated N- and O-linked sugars. 26914640 2 17 theme β-hydroxyenduracididines 292:315 arg1 pair 270:273 a pair 268:273 a pair of unprecedented β-hydroxyenduracididines (L- and D-βhEnd), an O-glycosylated D-Tyr carrying an α-linked dimannose, 268:389 Their cyclic hexapeptide core features a pair of unprecedented β-hydroxyenduracididines (L- and D-βhEnd), an O-glycosylated D-Tyr carrying an α-linked dimannose, and a β-methylated Phe residue. 26914640 2 17 theme β-hydroxyenduracididines 292:315 arg1 features 259:266 Their cyclic hexapeptide core features 229:266 Their cyclic hexapeptide core features a pair of unprecedented β-hydroxyenduracididines (L- and D-βhEnd), an O-glycosylated D-Tyr carrying an α-linked dimannose, and a β-methylated Phe residue. 229:421 Their cyclic hexapeptide core features a pair of unprecedented β-hydroxyenduracididines (L- and D-βhEnd), an O-glycosylated D-Tyr carrying an α-linked dimannose, and a β-methylated Phe residue. 26914640 2 17 theme β-hydroxyenduracididines 292:315 arg1 residue 414:420 a β-methylated Phe residue 395:420 a β-methylated Phe residue 395:420 Their cyclic hexapeptide core features a pair of unprecedented β-hydroxyenduracididines (L- and D-βhEnd), an O-glycosylated D-Tyr carrying an α-linked dimannose, and a β-methylated Phe residue. 26914640 2 17 theme β-hydroxyenduracididines 292:315 arg1 β-hydroxyenduracididines 292:315 unprecedented β-hydroxyenduracididines 278:315 unprecedented β-hydroxyenduracididines (L- and D-βhEnd) 278:332 Their cyclic hexapeptide core features a pair of unprecedented β-hydroxyenduracididines (L- and D-βhEnd), an O-glycosylated D-Tyr carrying an α-linked dimannose, and a β-methylated Phe residue. 26914640 2 18 theme Phe 410:412 arg1 features 259:266 Their cyclic hexapeptide core features 229:266 Their cyclic hexapeptide core features a pair of unprecedented β-hydroxyenduracididines (L- and D-βhEnd), an O-glycosylated D-Tyr carrying an α-linked dimannose, and a β-methylated Phe residue. 229:421 Their cyclic hexapeptide core features a pair of unprecedented β-hydroxyenduracididines (L- and D-βhEnd), an O-glycosylated D-Tyr carrying an α-linked dimannose, and a β-methylated Phe residue. 26914640 2 18 theme Phe 410:412 arg1 residue 414:420 a β-methylated Phe residue 395:420 a β-methylated Phe residue 395:420 Their cyclic hexapeptide core features a pair of unprecedented β-hydroxyenduracididines (L- and D-βhEnd), an O-glycosylated D-Tyr carrying an α-linked dimannose, and a β-methylated Phe residue. 26914640 2 18 theme Phe 410:412 arg1 β-hydroxyenduracididines 292:315 unprecedented β-hydroxyenduracididines 278:315 unprecedented β-hydroxyenduracididines (L- and D-βhEnd) 278:332 Their cyclic hexapeptide core features a pair of unprecedented β-hydroxyenduracididines (L- and D-βhEnd), an O-glycosylated D-Tyr carrying an α-linked dimannose, and a β-methylated Phe residue. 26914640 1 19 gly glycopeptide 81:92 arg2 glycopeptide 81:92 glycopeptide 81:92 glycopeptide 81:92 The mannopeptimycins are a class of glycopeptide natural products with unusual structures and potent antibiotic activity against a range of Gram-positive multidrug-resistant bacteria. 26914640 2 20 theme unprecedented 278:290 arg1 D-Tyr 353:357 an O-glycosylated D-Tyr 335:357 an O-glycosylated D-Tyr carrying an α-linked dimannose 335:388 Their cyclic hexapeptide core features a pair of unprecedented β-hydroxyenduracididines (L- and D-βhEnd), an O-glycosylated D-Tyr carrying an α-linked dimannose, and a β-methylated Phe residue. 26914640 2 20 theme unprecedented 278:290 arg1 β-hydroxyenduracididines 292:315 unprecedented β-hydroxyenduracididines 278:315 unprecedented β-hydroxyenduracididines (L- and D-βhEnd) 278:332 Their cyclic hexapeptide core features a pair of unprecedented β-hydroxyenduracididines (L- and D-βhEnd), an O-glycosylated D-Tyr carrying an α-linked dimannose, and a β-methylated Phe residue. 26914640 2 21 theme β-methylated 397:408 arg1 features 259:266 Their cyclic hexapeptide core features 229:266 Their cyclic hexapeptide core features a pair of unprecedented β-hydroxyenduracididines (L- and D-βhEnd), an O-glycosylated D-Tyr carrying an α-linked dimannose, and a β-methylated Phe residue. 229:421 Their cyclic hexapeptide core features a pair of unprecedented β-hydroxyenduracididines (L- and D-βhEnd), an O-glycosylated D-Tyr carrying an α-linked dimannose, and a β-methylated Phe residue. 26914640 2 21 theme β-methylated 397:408 arg1 residue 414:420 a β-methylated Phe residue 395:420 a β-methylated Phe residue 395:420 Their cyclic hexapeptide core features a pair of unprecedented β-hydroxyenduracididines (L- and D-βhEnd), an O-glycosylated D-Tyr carrying an α-linked dimannose, and a β-methylated Phe residue. 26914640 2 21 theme β-methylated 397:408 arg1 β-hydroxyenduracididines 292:315 unprecedented β-hydroxyenduracididines 278:315 unprecedented β-hydroxyenduracididines (L- and D-βhEnd) 278:332 Their cyclic hexapeptide core features a pair of unprecedented β-hydroxyenduracididines (L- and D-βhEnd), an O-glycosylated D-Tyr carrying an α-linked dimannose, and a β-methylated Phe residue. 26914640 5 22 theme unit 821:824 arg1 synthesis 773:781 the synthesis 769:781 the synthesis of the most challenging N-Man-D-βhEnd unit with excellent efficiency and stereoselectivity 769:872 Critically, a gold-catalyzed N-glycosylation of a D-βhEnd substrate with a mannosyl ortho-alkynylbenzoate donor enabled the synthesis of the most challenging N-Man-D-βhEnd unit with excellent efficiency and stereoselectivity. 26914640 6 23 theme arylation 931:939 arg1 method 941:946 a Pd-catalyzed C-H arylation method 912:946 a Pd-catalyzed C-H arylation method 912:946 The L-βMePhe unit was prepared using a Pd-catalyzed C-H arylation method. 26914640 5 24 gly N-glycosylation 678:692 arg1 substrate 707:715 a D-βhEnd substrate 697:715 a D-βhEnd substrate with a mannosyl ortho-alkynylbenzoate donor 697:759 Critically, a gold-catalyzed N-glycosylation of a D-βhEnd substrate with a mannosyl ortho-alkynylbenzoate donor enabled the synthesis of the most challenging N-Man-D-βhEnd unit with excellent efficiency and stereoselectivity. 26914640 8 25 theme hydrogenolysis 1103:1116 arg1 operation 1131:1139 a single global hydrogenolysis deprotection operation 1087:1139 a single global hydrogenolysis deprotection operation 1087:1139 A convergent assembly of the cyclic peptide scaffold and a single global hydrogenolysis deprotection operation provided mannopeptimycin α and β. 26914640 4 26 theme O-linked 632:639 arg1 sugars 641:646 O-linked sugars 632:646 O-linked sugars 632:646 Herein, we report the first total synthesis of mannopeptimycin α and β with fully elaborated N- and O-linked sugars. 26914640 0 27 theme Total 0:4 arg1 Synthesis 6:14 Total Synthesis 0:14 Total Synthesis of Mannopeptimycins α and β. 0:43 Total Synthesis of Mannopeptimycins α and β. 26914640 0 28 theme Mannopeptimycins 19:34 arg1 Synthesis 6:14 Total Synthesis 0:14 Total Synthesis of Mannopeptimycins α and β. 0:43 Total Synthesis of Mannopeptimycins α and β. 26914640 1 29 with class 72:76 arg1 structures 124:133 unusual structures 116:133 unusual structures 116:133 The mannopeptimycins are a class of glycopeptide natural products with unusual structures and potent antibiotic activity against a range of Gram-positive multidrug-resistant bacteria. 26914640 1 29 with class 72:76 arg1 activity 157:164 potent antibiotic activity 139:164 potent antibiotic activity 139:164 The mannopeptimycins are a class of glycopeptide natural products with unusual structures and potent antibiotic activity against a range of Gram-positive multidrug-resistant bacteria. 26914640 1 30 theme glycopeptide 81:92 arg1 products 102:109 glycopeptide natural products 81:109 glycopeptide natural products 81:109 The mannopeptimycins are a class of glycopeptide natural products with unusual structures and potent antibiotic activity against a range of Gram-positive multidrug-resistant bacteria. 26914640 1 31 theme Gram-positive 185:197 arg1 bacteria 219:226 Gram-positive multidrug-resistant bacteria 185:226 Gram-positive multidrug-resistant bacteria 185:226 The mannopeptimycins are a class of glycopeptide natural products with unusual structures and potent antibiotic activity against a range of Gram-positive multidrug-resistant bacteria. 26914640 4 32 theme total 560:564 arg1 synthesis 566:574 the first total synthesis 550:574 the first total synthesis of mannopeptimycin α and β with fully elaborated N- and O-linked sugars 550:646 Herein, we report the first total synthesis of mannopeptimycin α and β with fully elaborated N- and O-linked sugars. 26914640 5 33 theme D-βhEnd 699:705 arg1 substrate 707:715 a D-βhEnd substrate 697:715 a D-βhEnd substrate with a mannosyl ortho-alkynylbenzoate donor 697:759 Critically, a gold-catalyzed N-glycosylation of a D-βhEnd substrate with a mannosyl ortho-alkynylbenzoate donor enabled the synthesis of the most challenging N-Man-D-βhEnd unit with excellent efficiency and stereoselectivity. 26914640 1 34 theme natural 94:100 arg1 products 102:109 glycopeptide natural products 81:109 glycopeptide natural products 81:109 The mannopeptimycins are a class of glycopeptide natural products with unusual structures and potent antibiotic activity against a range of Gram-positive multidrug-resistant bacteria. 26914640 1 35 theme multidrug-resistant 199:217 arg1 bacteria 219:226 Gram-positive multidrug-resistant bacteria 185:226 Gram-positive multidrug-resistant bacteria 185:226 The mannopeptimycins are a class of glycopeptide natural products with unusual structures and potent antibiotic activity against a range of Gram-positive multidrug-resistant bacteria. 26914640 4 36 theme first 554:558 arg1 synthesis 566:574 the first total synthesis 550:574 the first total synthesis of mannopeptimycin α and β with fully elaborated N- and O-linked sugars 550:646 Herein, we report the first total synthesis of mannopeptimycin α and β with fully elaborated N- and O-linked sugars. 26914640 5 37 theme substrate 707:715 arg1 N-glycosylation 678:692 a gold-catalyzed N-glycosylation 661:692 a gold-catalyzed N-glycosylation of a D-βhEnd substrate with a mannosyl ortho-alkynylbenzoate donor 661:759 Critically, a gold-catalyzed N-glycosylation of a D-βhEnd substrate with a mannosyl ortho-alkynylbenzoate donor enabled the synthesis of the most challenging N-Man-D-βhEnd unit with excellent efficiency and stereoselectivity. 26914640 3 38 theme α-linked 456:463 arg1 mannopyranose 465:477 an α-linked mannopyranose 453:477 an α-linked mannopyranose 453:477 The D-βhEnd unit also carries an α-linked mannopyranose at the most hindered N of its cyclic guanidine ring. 26914640 2 39 theme core 254:257 arg1 pair 270:273 a pair 268:273 a pair of unprecedented β-hydroxyenduracididines (L- and D-βhEnd), an O-glycosylated D-Tyr carrying an α-linked dimannose, 268:389 Their cyclic hexapeptide core features a pair of unprecedented β-hydroxyenduracididines (L- and D-βhEnd), an O-glycosylated D-Tyr carrying an α-linked dimannose, and a β-methylated Phe residue. 26914640 2 39 theme core 254:257 arg1 residue 414:420 a β-methylated Phe residue 395:420 a β-methylated Phe residue 395:420 Their cyclic hexapeptide core features a pair of unprecedented β-hydroxyenduracididines (L- and D-βhEnd), an O-glycosylated D-Tyr carrying an α-linked dimannose, and a β-methylated Phe residue. 26914640 2 39 theme core 254:257 arg1 features 259:266 Their cyclic hexapeptide core features 229:266 Their cyclic hexapeptide core features a pair of unprecedented β-hydroxyenduracididines (L- and D-βhEnd), an O-glycosylated D-Tyr carrying an α-linked dimannose, and a β-methylated Phe residue. 229:421 Their cyclic hexapeptide core features a pair of unprecedented β-hydroxyenduracididines (L- and D-βhEnd), an O-glycosylated D-Tyr carrying an α-linked dimannose, and a β-methylated Phe residue. 26914640 2 39 theme core 254:257 arg1 β-hydroxyenduracididines 292:315 unprecedented β-hydroxyenduracididines 278:315 unprecedented β-hydroxyenduracididines (L- and D-βhEnd) 278:332 Their cyclic hexapeptide core features a pair of unprecedented β-hydroxyenduracididines (L- and D-βhEnd), an O-glycosylated D-Tyr carrying an α-linked dimannose, and a β-methylated Phe residue. 26914640 1 40 theme bacteria 219:226 arg1 range 176:180 a range 174:180 a range of Gram-positive multidrug-resistant bacteria 174:226 The mannopeptimycins are a class of glycopeptide natural products with unusual structures and potent antibiotic activity against a range of Gram-positive multidrug-resistant bacteria. 26914640 3 41 theme D-βhEnd 427:433 arg1 unit 435:438 The D-βhEnd unit 423:438 The D-βhEnd unit 423:438 The D-βhEnd unit also carries an α-linked mannopyranose at the most hindered N of its cyclic guanidine ring. 26914640 8 42 theme single 1089:1094 arg1 operation 1131:1139 a single global hydrogenolysis deprotection operation 1087:1139 a single global hydrogenolysis deprotection operation 1087:1139 A convergent assembly of the cyclic peptide scaffold and a single global hydrogenolysis deprotection operation provided mannopeptimycin α and β. 26914640 2 43 theme hexapeptide 242:252 arg1 pair 270:273 a pair 268:273 a pair of unprecedented β-hydroxyenduracididines (L- and D-βhEnd), an O-glycosylated D-Tyr carrying an α-linked dimannose, 268:389 Their cyclic hexapeptide core features a pair of unprecedented β-hydroxyenduracididines (L- and D-βhEnd), an O-glycosylated D-Tyr carrying an α-linked dimannose, and a β-methylated Phe residue. 26914640 2 43 theme hexapeptide 242:252 arg1 residue 414:420 a β-methylated Phe residue 395:420 a β-methylated Phe residue 395:420 Their cyclic hexapeptide core features a pair of unprecedented β-hydroxyenduracididines (L- and D-βhEnd), an O-glycosylated D-Tyr carrying an α-linked dimannose, and a β-methylated Phe residue. 26914640 2 43 theme hexapeptide 242:252 arg1 features 259:266 Their cyclic hexapeptide core features 229:266 Their cyclic hexapeptide core features a pair of unprecedented β-hydroxyenduracididines (L- and D-βhEnd), an O-glycosylated D-Tyr carrying an α-linked dimannose, and a β-methylated Phe residue. 229:421 Their cyclic hexapeptide core features a pair of unprecedented β-hydroxyenduracididines (L- and D-βhEnd), an O-glycosylated D-Tyr carrying an α-linked dimannose, and a β-methylated Phe residue. 26914640 2 43 theme hexapeptide 242:252 arg1 β-hydroxyenduracididines 292:315 unprecedented β-hydroxyenduracididines 278:315 unprecedented β-hydroxyenduracididines (L- and D-βhEnd) 278:332 Their cyclic hexapeptide core features a pair of unprecedented β-hydroxyenduracididines (L- and D-βhEnd), an O-glycosylated D-Tyr carrying an α-linked dimannose, and a β-methylated Phe residue. 26914640 5 44 theme excellent 831:839 arg1 efficiency 841:850 excellent efficiency 831:850 excellent efficiency 831:850 Critically, a gold-catalyzed N-glycosylation of a D-βhEnd substrate with a mannosyl ortho-alkynylbenzoate donor enabled the synthesis of the most challenging N-Man-D-βhEnd unit with excellent efficiency and stereoselectivity. 26914640 5 45 theme challenging 795:805 arg1 unit 821:824 the most challenging N-Man-D-βhEnd unit 786:824 the most challenging N-Man-D-βhEnd unit with excellent efficiency and stereoselectivity 786:872 Critically, a gold-catalyzed N-glycosylation of a D-βhEnd substrate with a mannosyl ortho-alkynylbenzoate donor enabled the synthesis of the most challenging N-Man-D-βhEnd unit with excellent efficiency and stereoselectivity. 26914640 8 46 theme deprotection 1118:1129 arg1 operation 1131:1139 a single global hydrogenolysis deprotection operation 1087:1139 a single global hydrogenolysis deprotection operation 1087:1139 A convergent assembly of the cyclic peptide scaffold and a single global hydrogenolysis deprotection operation provided mannopeptimycin α and β. 26914640 6 47 theme L-βMePhe 879:886 arg1 unit 888:891 The L-βMePhe unit 875:891 The L-βMePhe unit 875:891 The L-βMePhe unit was prepared using a Pd-catalyzed C-H arylation method. 26914640 2 48 theme cyclic 235:240 arg1 pair 270:273 a pair 268:273 a pair of unprecedented β-hydroxyenduracididines (L- and D-βhEnd), an O-glycosylated D-Tyr carrying an α-linked dimannose, 268:389 Their cyclic hexapeptide core features a pair of unprecedented β-hydroxyenduracididines (L- and D-βhEnd), an O-glycosylated D-Tyr carrying an α-linked dimannose, and a β-methylated Phe residue. 26914640 2 48 theme cyclic 235:240 arg1 residue 414:420 a β-methylated Phe residue 395:420 a β-methylated Phe residue 395:420 Their cyclic hexapeptide core features a pair of unprecedented β-hydroxyenduracididines (L- and D-βhEnd), an O-glycosylated D-Tyr carrying an α-linked dimannose, and a β-methylated Phe residue. 26914640 2 48 theme cyclic 235:240 arg1 features 259:266 Their cyclic hexapeptide core features 229:266 Their cyclic hexapeptide core features a pair of unprecedented β-hydroxyenduracididines (L- and D-βhEnd), an O-glycosylated D-Tyr carrying an α-linked dimannose, and a β-methylated Phe residue. 229:421 Their cyclic hexapeptide core features a pair of unprecedented β-hydroxyenduracididines (L- and D-βhEnd), an O-glycosylated D-Tyr carrying an α-linked dimannose, and a β-methylated Phe residue. 26914640 2 48 theme cyclic 235:240 arg1 β-hydroxyenduracididines 292:315 unprecedented β-hydroxyenduracididines 278:315 unprecedented β-hydroxyenduracididines (L- and D-βhEnd) 278:332 Their cyclic hexapeptide core features a pair of unprecedented β-hydroxyenduracididines (L- and D-βhEnd), an O-glycosylated D-Tyr carrying an α-linked dimannose, and a β-methylated Phe residue. 26914640 1 49 theme products 102:109 arg1 mannopeptimycins 49:64 The mannopeptimycins 45:64 The mannopeptimycins 45:64 The mannopeptimycins are a class of glycopeptide natural products with unusual structures and potent antibiotic activity against a range of Gram-positive multidrug-resistant bacteria. 26914640 1 49 theme products 102:109 arg1 class 72:76 a class 70:76 a class of glycopeptide natural products with unusual structures and potent antibiotic activity 70:164 The mannopeptimycins are a class of glycopeptide natural products with unusual structures and potent antibiotic activity against a range of Gram-positive multidrug-resistant bacteria. 26914640 5 50 theme N-Man-D-βhEnd 807:819 arg1 unit 821:824 the most challenging N-Man-D-βhEnd unit 786:824 the most challenging N-Man-D-βhEnd unit with excellent efficiency and stereoselectivity 786:872 Critically, a gold-catalyzed N-glycosylation of a D-βhEnd substrate with a mannosyl ortho-alkynylbenzoate donor enabled the synthesis of the most challenging N-Man-D-βhEnd unit with excellent efficiency and stereoselectivity. 26914640 5 51 theme gold-catalyzed 663:676 arg1 N-glycosylation 678:692 a gold-catalyzed N-glycosylation 661:692 a gold-catalyzed N-glycosylation of a D-βhEnd substrate with a mannosyl ortho-alkynylbenzoate donor 661:759 Critically, a gold-catalyzed N-glycosylation of a D-βhEnd substrate with a mannosyl ortho-alkynylbenzoate donor enabled the synthesis of the most challenging N-Man-D-βhEnd unit with excellent efficiency and stereoselectivity. 26914640 8 52 theme global 1096:1101 arg1 operation 1131:1139 a single global hydrogenolysis deprotection operation 1087:1139 a single global hydrogenolysis deprotection operation 1087:1139 A convergent assembly of the cyclic peptide scaffold and a single global hydrogenolysis deprotection operation provided mannopeptimycin α and β. 26914640 4 53 link O-linked 632:639 arg1 sugars 641:646 O-linked sugars 632:646 O-linked sugars 632:646 Herein, we report the first total synthesis of mannopeptimycin α and β with fully elaborated N- and O-linked sugars. 26914640 0 54 dep Mannopeptimycins 19:34 arg1 β 42:42 β 42:42 β 42:42 Total Synthesis of Mannopeptimycins α and β. 26914640 0 54 dep Mannopeptimycins 19:34 arg1 α 36:36 α 36:36 α 36:36 Total Synthesis of Mannopeptimycins α and β. 26914640 7 55 theme gram 1013:1016 arg1 quantities 1018:1027 gram quantities 1013:1027 gram quantities 1013:1027 The L-βhEnd, D-Tyr(di-Man), and L-βMePhe units were prepared in gram quantities. 26914640 1 56 theme unusual 116:122 arg1 structures 124:133 unusual structures 116:133 unusual structures 116:133 The mannopeptimycins are a class of glycopeptide natural products with unusual structures and potent antibiotic activity against a range of Gram-positive multidrug-resistant bacteria. 26914640 5 57 with unit 821:824 arg1 stereoselectivity 856:872 stereoselectivity 856:872 stereoselectivity 856:872 Critically, a gold-catalyzed N-glycosylation of a D-βhEnd substrate with a mannosyl ortho-alkynylbenzoate donor enabled the synthesis of the most challenging N-Man-D-βhEnd unit with excellent efficiency and stereoselectivity. 26914640 5 57 with unit 821:824 arg1 efficiency 841:850 excellent efficiency 831:850 excellent efficiency 831:850 Critically, a gold-catalyzed N-glycosylation of a D-βhEnd substrate with a mannosyl ortho-alkynylbenzoate donor enabled the synthesis of the most challenging N-Man-D-βhEnd unit with excellent efficiency and stereoselectivity. 26914640 4 58 theme β 601:601 arg1 synthesis 566:574 the first total synthesis 550:574 the first total synthesis of mannopeptimycin α and β with fully elaborated N- and O-linked sugars 550:646 Herein, we report the first total synthesis of mannopeptimycin α and β with fully elaborated N- and O-linked sugars. 26914640 2 59 gly O-glycosylated 338:351 arg1 D-Tyr 353:357 an O-glycosylated D-Tyr 335:357 an O-glycosylated D-Tyr carrying an α-linked dimannose 335:388 Their cyclic hexapeptide core features a pair of unprecedented β-hydroxyenduracididines (L- and D-βhEnd), an O-glycosylated D-Tyr carrying an α-linked dimannose, and a β-methylated Phe residue. 26914640 2 59 gly O-glycosylated 338:351 arg1 β-hydroxyenduracididines 292:315 unprecedented β-hydroxyenduracididines 278:315 unprecedented β-hydroxyenduracididines (L- and D-βhEnd) 278:332 Their cyclic hexapeptide core features a pair of unprecedented β-hydroxyenduracididines (L- and D-βhEnd), an O-glycosylated D-Tyr carrying an α-linked dimannose, and a β-methylated Phe residue. 26914640 3 60 theme ring 526:529 arg1 N 500:500 the most hindered N 482:500 the most hindered N of its cyclic guanidine ring 482:529 The D-βhEnd unit also carries an α-linked mannopyranose at the most hindered N of its cyclic guanidine ring. 26914640 2 61 theme O-glycosylated 338:351 arg1 D-Tyr 353:357 an O-glycosylated D-Tyr 335:357 an O-glycosylated D-Tyr carrying an α-linked dimannose 335:388 Their cyclic hexapeptide core features a pair of unprecedented β-hydroxyenduracididines (L- and D-βhEnd), an O-glycosylated D-Tyr carrying an α-linked dimannose, and a β-methylated Phe residue. 26914640 2 61 theme O-glycosylated 338:351 arg1 β-hydroxyenduracididines 292:315 unprecedented β-hydroxyenduracididines 278:315 unprecedented β-hydroxyenduracididines (L- and D-βhEnd) 278:332 Their cyclic hexapeptide core features a pair of unprecedented β-hydroxyenduracididines (L- and D-βhEnd), an O-glycosylated D-Tyr carrying an α-linked dimannose, and a β-methylated Phe residue. 26914640 8 62 theme peptide 1066:1072 arg1 scaffold 1074:1081 the cyclic peptide scaffold 1055:1081 the cyclic peptide scaffold 1055:1081 A convergent assembly of the cyclic peptide scaffold and a single global hydrogenolysis deprotection operation provided mannopeptimycin α and β. 26914640 3 63 contain carries 445:451 arg3 N 500:500 the most hindered N 482:500 the most hindered N of its cyclic guanidine ring 482:529 The D-βhEnd unit also carries an α-linked mannopyranose at the most hindered N of its cyclic guanidine ring. 26914640 3 63 contain carries 445:451 arg1 unit 435:438 The D-βhEnd unit 423:438 The D-βhEnd unit 423:438 The D-βhEnd unit also carries an α-linked mannopyranose at the most hindered N of its cyclic guanidine ring. 26914640 3 63 contain carries 445:451 arg2 mannopyranose 465:477 an α-linked mannopyranose 453:477 an α-linked mannopyranose 453:477 The D-βhEnd unit also carries an α-linked mannopyranose at the most hindered N of its cyclic guanidine ring. 26914640 5 64 with substrate 707:715 arg1 donor 755:759 a mannosyl ortho-alkynylbenzoate donor 722:759 a mannosyl ortho-alkynylbenzoate donor 722:759 Critically, a gold-catalyzed N-glycosylation of a D-βhEnd substrate with a mannosyl ortho-alkynylbenzoate donor enabled the synthesis of the most challenging N-Man-D-βhEnd unit with excellent efficiency and stereoselectivity. 26914640 2 65 dep β-hydroxyenduracididines 292:315 arg1 D-βhEnd 325:331 D-βhEnd 325:331 D-βhEnd 325:331 Their cyclic hexapeptide core features a pair of unprecedented β-hydroxyenduracididines (L- and D-βhEnd), an O-glycosylated D-Tyr carrying an α-linked dimannose, and a β-methylated Phe residue. 26914640 2 65 dep β-hydroxyenduracididines 292:315 arg1 L- 318:319 L- 318:319 L- 318:319 Their cyclic hexapeptide core features a pair of unprecedented β-hydroxyenduracididines (L- and D-βhEnd), an O-glycosylated D-Tyr carrying an α-linked dimannose, and a β-methylated Phe residue. 26914640 2 66 dep features 259:266 arg1 pair 270:273 a pair 268:273 a pair of unprecedented β-hydroxyenduracididines (L- and D-βhEnd), an O-glycosylated D-Tyr carrying an α-linked dimannose, 268:389 Their cyclic hexapeptide core features a pair of unprecedented β-hydroxyenduracididines (L- and D-βhEnd), an O-glycosylated D-Tyr carrying an α-linked dimannose, and a β-methylated Phe residue. 26914640 2 66 dep features 259:266 arg1 features 259:266 Their cyclic hexapeptide core features 229:266 Their cyclic hexapeptide core features a pair of unprecedented β-hydroxyenduracididines (L- and D-βhEnd), an O-glycosylated D-Tyr carrying an α-linked dimannose, and a β-methylated Phe residue. 229:421 Their cyclic hexapeptide core features a pair of unprecedented β-hydroxyenduracididines (L- and D-βhEnd), an O-glycosylated D-Tyr carrying an α-linked dimannose, and a β-methylated Phe residue. 26914640 2 66 dep features 259:266 arg1 residue 414:420 a β-methylated Phe residue 395:420 a β-methylated Phe residue 395:420 Their cyclic hexapeptide core features a pair of unprecedented β-hydroxyenduracididines (L- and D-βhEnd), an O-glycosylated D-Tyr carrying an α-linked dimannose, and a β-methylated Phe residue. 26914640 2 66 dep features 259:266 arg1 β-hydroxyenduracididines 292:315 unprecedented β-hydroxyenduracididines 278:315 unprecedented β-hydroxyenduracididines (L- and D-βhEnd) 278:332 Their cyclic hexapeptide core features a pair of unprecedented β-hydroxyenduracididines (L- and D-βhEnd), an O-glycosylated D-Tyr carrying an α-linked dimannose, and a β-methylated Phe residue. 26914640 4 67 theme mannopeptimycin 579:593 arg1 α 595:595 mannopeptimycin α 579:595 mannopeptimycin α 579:595 Herein, we report the first total synthesis of mannopeptimycin α and β with fully elaborated N- and O-linked sugars. 26914640 8 68 theme mannopeptimycin 1150:1164 arg1 α 1166:1166 mannopeptimycin α 1150:1166 mannopeptimycin α 1150:1166 A convergent assembly of the cyclic peptide scaffold and a single global hydrogenolysis deprotection operation provided mannopeptimycin α and β. 26914640 4 69 with synthesis 566:574 arg1 N- 625:626 fully elaborated N- 608:626 fully elaborated N- 608:626 Herein, we report the first total synthesis of mannopeptimycin α and β with fully elaborated N- and O-linked sugars. 26914640 4 69 with synthesis 566:574 arg1 sugars 641:646 O-linked sugars 632:646 O-linked sugars 632:646 Herein, we report the first total synthesis of mannopeptimycin α and β with fully elaborated N- and O-linked sugars. 26914640 7 70 theme L-βMePhe 981:988 arg1 units 990:994 L-βMePhe units 981:994 L-βMePhe units 981:994 The L-βhEnd, D-Tyr(di-Man), and L-βMePhe units were prepared in gram quantities. 26914640 1 71 theme potent 139:144 arg1 activity 157:164 potent antibiotic activity 139:164 potent antibiotic activity 139:164 The mannopeptimycins are a class of glycopeptide natural products with unusual structures and potent antibiotic activity against a range of Gram-positive multidrug-resistant bacteria. 24615797 8 0 from diastereoselectivity 1375:1394 arg1 cycle 1263:1267 the catalytic cycle 1249:1267 the catalytic cycle 1249:1267 This mechanistic study rationalizes the order in which the unsaturations take part in the catalytic cycle, the reactivity of the two double bonds of the allene towards the [2+2+2] cycloaddition reaction, and the diastereoselectivity of the reaction. 24615797 5 1 theme bond 836:839 arg1 reaction 800:807 a regioselective reaction 783:807 a regioselective reaction of the inner allene double bond and, therefore, feature an exocyclic diene motif 783:888 All cycloadducts were formed by a regioselective reaction of the inner allene double bond and, therefore, feature an exocyclic diene motif. 24615797 6 2 dep cycloadducts 932:943 arg1 10 951:952 10 951:952 10 951:952 A Diels-Alder reaction on N-tosyl linked cycloadducts 8 and 10 allowed pentacyclic scaffolds to be diastereoselectively constructed. 24615797 6 2 dep cycloadducts 932:943 arg1 8 945:945 8 945:945 8 945:945 A Diels-Alder reaction on N-tosyl linked cycloadducts 8 and 10 allowed pentacyclic scaffolds to be diastereoselectively constructed. 24615797 1 3 link O-linked 220:227 arg1 substrates 229:238 N-tosyl and O-linked substrates 208:238 N-tosyl and O-linked substrates 208:238 Allene-ene-allene (2 and 5) and allene-yne-allene (3 and 7) N-tosyl and O-linked substrates were satisfactorily synthesised. 24615797 8 4 theme mechanistic 1168:1178 arg1 study 1180:1184 This mechanistic study 1163:1184 This mechanistic study 1163:1184 This mechanistic study rationalizes the order in which the unsaturations take part in the catalytic cycle, the reactivity of the two double bonds of the allene towards the [2+2+2] cycloaddition reaction, and the diastereoselectivity of the reaction. 24615797 4 5 theme central 637:643 arg1 position 645:652 the central position 633:652 the central position 633:652 The reaction of substrates 3 and 7, which bear a triple bond in the central position, gave a tricyclic structure with a cyclohexenic ring core, again in a diastereoselective manner. 24615797 6 6 theme linked 925:930 arg1 cycloadducts 932:943 N-tosyl linked cycloadducts 8 and 10 917:952 N-tosyl linked cycloadducts 8 and 10 917:952 A Diels-Alder reaction on N-tosyl linked cycloadducts 8 and 10 allowed pentacyclic scaffolds to be diastereoselectively constructed. 24615797 0 7 theme mechanistic 127:137 arg1 studies 139:145 theoretical mechanistic studies 115:145 theoretical mechanistic studies 115:145 Stereoselective rhodium-catalysed [2+2+2] cycloaddition of linear allene-ene/yne-allene substrates: reactivity and theoretical mechanistic studies. 24615797 8 8 theme cycloaddition 1343:1355 arg1 reaction 1357:1364 the [2+2+2] cycloaddition reaction 1331:1364 the [2+2+2] cycloaddition reaction 1331:1364 This mechanistic study rationalizes the order in which the unsaturations take part in the catalytic cycle, the reactivity of the two double bonds of the allene towards the [2+2+2] cycloaddition reaction, and the diastereoselectivity of the reaction. 24615797 3 9 theme stereogenic 511:521 arg1 centres 523:529 four contiguous stereogenic centres 495:529 four contiguous stereogenic centres 495:529 Substrates 2 and 5, which bear a double bond in the central position, gave a tricyclic structure in a reaction in which four contiguous stereogenic centres were formed as a single diastereomer. 24615797 3 9 theme stereogenic 511:521 arg1 diastereomer 555:566 a single diastereomer 546:566 a single diastereomer 546:566 Substrates 2 and 5, which bear a double bond in the central position, gave a tricyclic structure in a reaction in which four contiguous stereogenic centres were formed as a single diastereomer. 24615797 6 10 theme N-tosyl 917:923 arg1 cycloadducts 932:943 N-tosyl linked cycloadducts 8 and 10 917:952 N-tosyl linked cycloadducts 8 and 10 917:952 A Diels-Alder reaction on N-tosyl linked cycloadducts 8 and 10 allowed pentacyclic scaffolds to be diastereoselectively constructed. 24615797 0 11 theme theoretical 115:125 arg1 studies 139:145 theoretical mechanistic studies 115:145 theoretical mechanistic studies 115:145 Stereoselective rhodium-catalysed [2+2+2] cycloaddition of linear allene-ene/yne-allene substrates: reactivity and theoretical mechanistic studies. 24615797 4 12 theme ring 702:705 arg1 core 707:710 a cyclohexenic ring core 687:710 a cyclohexenic ring core 687:710 The reaction of substrates 3 and 7, which bear a triple bond in the central position, gave a tricyclic structure with a cyclohexenic ring core, again in a diastereoselective manner. 24615797 4 13 from bond 625:628 arg1 position 645:652 the central position 633:652 the central position 633:652 The reaction of substrates 3 and 7, which bear a triple bond in the central position, gave a tricyclic structure with a cyclohexenic ring core, again in a diastereoselective manner. 24615797 7 14 theme density 1123:1129 arg1 calculations 1149:1160 density functional theory calculations 1123:1160 density functional theory calculations 1123:1160 The reactivity of the allenes on [2+2+2] cycloaddition reactions was studied for the first time by density functional theory calculations. 24615797 7 15 theme first 1109:1113 arg1 time 1115:1118 the first time 1105:1118 the first time 1105:1118 The reactivity of the allenes on [2+2+2] cycloaddition reactions was studied for the first time by density functional theory calculations. 24615797 3 16 contain bear 401:404 arg1 Substrates 375:384 Substrates 2 and 5 375:392 Substrates 2 and 5 375:392 Substrates 2 and 5, which bear a double bond in the central position, gave a tricyclic structure in a reaction in which four contiguous stereogenic centres were formed as a single diastereomer. 24615797 3 16 contain bear 401:404 arg2 bond 415:418 a double bond 406:418 a double bond in the central position 406:442 Substrates 2 and 5, which bear a double bond in the central position, gave a tricyclic structure in a reaction in which four contiguous stereogenic centres were formed as a single diastereomer. 24615797 1 17 dep Allene-ene-allene 148:164 arg1 2 167:167 2 167:167 2 167:167 Allene-ene-allene (2 and 5) and allene-yne-allene (3 and 7) N-tosyl and O-linked substrates were satisfactorily synthesised. 24615797 1 17 dep Allene-ene-allene 148:164 arg1 substrates 229:238 N-tosyl and O-linked substrates 208:238 N-tosyl and O-linked substrates 208:238 Allene-ene-allene (2 and 5) and allene-yne-allene (3 and 7) N-tosyl and O-linked substrates were satisfactorily synthesised. 24615797 1 17 dep Allene-ene-allene 148:164 arg1 5 173:173 5 173:173 5 173:173 Allene-ene-allene (2 and 5) and allene-yne-allene (3 and 7) N-tosyl and O-linked substrates were satisfactorily synthesised. 24615797 7 18 theme functional 1131:1140 arg1 calculations 1149:1160 density functional theory calculations 1123:1160 density functional theory calculations 1123:1160 The reactivity of the allenes on [2+2+2] cycloaddition reactions was studied for the first time by density functional theory calculations. 24615797 5 19 dep therefore 846:854 arg1 feature 857:863 feature 857:863 feature 857:863 All cycloadducts were formed by a regioselective reaction of the inner allene double bond and, therefore, feature an exocyclic diene motif. 24615797 8 20 from reactivity 1274:1283 arg1 cycle 1263:1267 the catalytic cycle 1249:1267 the catalytic cycle 1249:1267 This mechanistic study rationalizes the order in which the unsaturations take part in the catalytic cycle, the reactivity of the two double bonds of the allene towards the [2+2+2] cycloaddition reaction, and the diastereoselectivity of the reaction. 24615797 2 21 theme cycloaddition 285:297 arg1 reaction 299:306 The [2+2+2] cycloaddition reaction 273:306 The [2+2+2] cycloaddition reaction catalysed by the Wilkinson catalyst [RhCl(PPh3 )3 ] 273:358 The [2+2+2] cycloaddition reaction catalysed by the Wilkinson catalyst [RhCl(PPh3 )3 ] was evaluated. 24615797 0 22 theme rhodium-catalysed 16:32 arg1 cycloaddition 42:54 Stereoselective rhodium-catalysed [2+2+2] cycloaddition 0:54 Stereoselective rhodium-catalysed [2+2+2] cycloaddition of linear allene-ene/yne-allene substrates: reactivity and theoretical mechanistic studies. 0:146 Stereoselective rhodium-catalysed [2+2+2] cycloaddition of linear allene-ene/yne-allene substrates: reactivity and theoretical mechanistic studies. 24615797 2 23 theme [RhCl 344:348 arg1 PPh3 350:353 the Wilkinson catalyst [RhCl(PPh3 )3 ] 321:358 the Wilkinson catalyst [RhCl(PPh3 )3 ] 321:358 The [2+2+2] cycloaddition reaction catalysed by the Wilkinson catalyst [RhCl(PPh3 )3 ] was evaluated. 24615797 3 24 theme double 408:413 arg1 bond 415:418 a double bond 406:418 a double bond in the central position 406:442 Substrates 2 and 5, which bear a double bond in the central position, gave a tricyclic structure in a reaction in which four contiguous stereogenic centres were formed as a single diastereomer. 24615797 0 25 theme Stereoselective 0:14 arg1 cycloaddition 42:54 Stereoselective rhodium-catalysed [2+2+2] cycloaddition 0:54 Stereoselective rhodium-catalysed [2+2+2] cycloaddition of linear allene-ene/yne-allene substrates: reactivity and theoretical mechanistic studies. 0:146 Stereoselective rhodium-catalysed [2+2+2] cycloaddition of linear allene-ene/yne-allene substrates: reactivity and theoretical mechanistic studies. 24615797 7 26 from reactivity 1028:1037 arg1 reactions 1079:1087 [2+2+2] cycloaddition reactions 1057:1087 [2+2+2] cycloaddition reactions 1057:1087 The reactivity of the allenes on [2+2+2] cycloaddition reactions was studied for the first time by density functional theory calculations. 24615797 2 27 theme catalyst 335:342 arg1 PPh3 350:353 the Wilkinson catalyst [RhCl(PPh3 )3 ] 321:358 the Wilkinson catalyst [RhCl(PPh3 )3 ] 321:358 The [2+2+2] cycloaddition reaction catalysed by the Wilkinson catalyst [RhCl(PPh3 )3 ] was evaluated. 24615797 8 28 theme double 1296:1301 arg1 bonds 1303:1307 the two double bonds 1288:1307 the two double bonds of the allene towards the [2+2+2] cycloaddition reaction 1288:1364 This mechanistic study rationalizes the order in which the unsaturations take part in the catalytic cycle, the reactivity of the two double bonds of the allene towards the [2+2+2] cycloaddition reaction, and the diastereoselectivity of the reaction. 24615797 4 29 theme triple 618:623 arg1 bond 625:628 a triple bond 616:628 a triple bond in the central position 616:652 The reaction of substrates 3 and 7, which bear a triple bond in the central position, gave a tricyclic structure with a cyclohexenic ring core, again in a diastereoselective manner. 24615797 6 30 theme Diels-Alder 893:903 arg1 reaction 905:912 A Diels-Alder reaction 891:912 A Diels-Alder reaction on N-tosyl linked cycloadducts 8 and 10 891:952 A Diels-Alder reaction on N-tosyl linked cycloadducts 8 and 10 allowed pentacyclic scaffolds to be diastereoselectively constructed. 24615797 8 31 theme [2+2+2 1335:1340 arg1 reaction 1357:1364 the [2+2+2] cycloaddition reaction 1331:1364 the [2+2+2] cycloaddition reaction 1331:1364 This mechanistic study rationalizes the order in which the unsaturations take part in the catalytic cycle, the reactivity of the two double bonds of the allene towards the [2+2+2] cycloaddition reaction, and the diastereoselectivity of the reaction. 24615797 2 32 theme Wilkinson 325:333 arg1 PPh3 350:353 the Wilkinson catalyst [RhCl(PPh3 )3 ] 321:358 the Wilkinson catalyst [RhCl(PPh3 )3 ] 321:358 The [2+2+2] cycloaddition reaction catalysed by the Wilkinson catalyst [RhCl(PPh3 )3 ] was evaluated. 24615797 7 33 theme allenes 1046:1052 arg1 reactivity 1028:1037 The reactivity 1024:1037 The reactivity of the allenes on [2+2+2] cycloaddition reactions 1024:1087 The reactivity of the allenes on [2+2+2] cycloaddition reactions was studied for the first time by density functional theory calculations. 24615797 1 34 dep allene-yne-allene 180:196 arg1 7 205:205 7 205:205 7 205:205 Allene-ene-allene (2 and 5) and allene-yne-allene (3 and 7) N-tosyl and O-linked substrates were satisfactorily synthesised. 24615797 1 34 dep allene-yne-allene 180:196 arg1 3 199:199 3 199:199 3 199:199 Allene-ene-allene (2 and 5) and allene-yne-allene (3 and 7) N-tosyl and O-linked substrates were satisfactorily synthesised. 24615797 5 35 theme exocyclic 868:876 arg1 motif 884:888 an exocyclic diene motif 865:888 an exocyclic diene motif 865:888 All cycloadducts were formed by a regioselective reaction of the inner allene double bond and, therefore, feature an exocyclic diene motif. 24615797 5 36 theme diene 878:882 arg1 motif 884:888 an exocyclic diene motif 865:888 an exocyclic diene motif 865:888 All cycloadducts were formed by a regioselective reaction of the inner allene double bond and, therefore, feature an exocyclic diene motif. 24615797 6 37 link linked 925:930 arg1 cycloadducts 932:943 N-tosyl linked cycloadducts 8 and 10 917:952 N-tosyl linked cycloadducts 8 and 10 917:952 A Diels-Alder reaction on N-tosyl linked cycloadducts 8 and 10 allowed pentacyclic scaffolds to be diastereoselectively constructed. 24615797 1 38 theme N-tosyl 208:214 arg1 substrates 229:238 N-tosyl and O-linked substrates 208:238 N-tosyl and O-linked substrates 208:238 Allene-ene-allene (2 and 5) and allene-yne-allene (3 and 7) N-tosyl and O-linked substrates were satisfactorily synthesised. 24615797 7 39 from allenes 1046:1052 arg1 reactions 1079:1087 [2+2+2] cycloaddition reactions 1057:1087 [2+2+2] cycloaddition reactions 1057:1087 The reactivity of the allenes on [2+2+2] cycloaddition reactions was studied for the first time by density functional theory calculations. 24615797 6 40 from reaction 905:912 arg1 cycloadducts 932:943 N-tosyl linked cycloadducts 8 and 10 917:952 N-tosyl linked cycloadducts 8 and 10 917:952 A Diels-Alder reaction on N-tosyl linked cycloadducts 8 and 10 allowed pentacyclic scaffolds to be diastereoselectively constructed. 24615797 5 41 theme inner 816:820 arg1 bond 836:839 the inner allene double bond 812:839 the inner allene double bond 812:839 All cycloadducts were formed by a regioselective reaction of the inner allene double bond and, therefore, feature an exocyclic diene motif. 24615797 3 42 theme central 427:433 arg1 position 435:442 the central position 423:442 the central position 423:442 Substrates 2 and 5, which bear a double bond in the central position, gave a tricyclic structure in a reaction in which four contiguous stereogenic centres were formed as a single diastereomer. 24615797 8 43 from part 1241:1244 arg1 cycle 1263:1267 the catalytic cycle 1249:1267 the catalytic cycle 1249:1267 This mechanistic study rationalizes the order in which the unsaturations take part in the catalytic cycle, the reactivity of the two double bonds of the allene towards the [2+2+2] cycloaddition reaction, and the diastereoselectivity of the reaction. 24615797 1 44 theme O-linked 220:227 arg1 substrates 229:238 N-tosyl and O-linked substrates 208:238 N-tosyl and O-linked substrates 208:238 Allene-ene-allene (2 and 5) and allene-yne-allene (3 and 7) N-tosyl and O-linked substrates were satisfactorily synthesised. 24615797 0 45 theme allene-ene/yne-allene 66:86 arg1 substrates 88:97 linear allene-ene/yne-allene substrates 59:97 linear allene-ene/yne-allene substrates 59:97 Stereoselective rhodium-catalysed [2+2+2] cycloaddition of linear allene-ene/yne-allene substrates: reactivity and theoretical mechanistic studies. 24615797 7 46 theme theory 1142:1147 arg1 calculations 1149:1160 density functional theory calculations 1123:1160 density functional theory calculations 1123:1160 The reactivity of the allenes on [2+2+2] cycloaddition reactions was studied for the first time by density functional theory calculations. 24615797 6 47 theme pentacyclic 962:972 arg1 scaffolds 974:982 pentacyclic scaffolds 962:982 pentacyclic scaffolds 962:982 A Diels-Alder reaction on N-tosyl linked cycloadducts 8 and 10 allowed pentacyclic scaffolds to be diastereoselectively constructed. 24615797 3 48 theme single 548:553 arg1 centres 523:529 four contiguous stereogenic centres 495:529 four contiguous stereogenic centres 495:529 Substrates 2 and 5, which bear a double bond in the central position, gave a tricyclic structure in a reaction in which four contiguous stereogenic centres were formed as a single diastereomer. 24615797 3 48 theme single 548:553 arg1 diastereomer 555:566 a single diastereomer 546:566 a single diastereomer 546:566 Substrates 2 and 5, which bear a double bond in the central position, gave a tricyclic structure in a reaction in which four contiguous stereogenic centres were formed as a single diastereomer. 24615797 8 49 theme bonds 1303:1307 arg1 part 1241:1244 part 1241:1244 part in the catalytic cycle 1241:1267 This mechanistic study rationalizes the order in which the unsaturations take part in the catalytic cycle, the reactivity of the two double bonds of the allene towards the [2+2+2] cycloaddition reaction, and the diastereoselectivity of the reaction. 24615797 8 49 theme bonds 1303:1307 arg1 diastereoselectivity 1375:1394 the diastereoselectivity 1371:1394 the diastereoselectivity of the reaction 1371:1410 This mechanistic study rationalizes the order in which the unsaturations take part in the catalytic cycle, the reactivity of the two double bonds of the allene towards the [2+2+2] cycloaddition reaction, and the diastereoselectivity of the reaction. 24615797 8 49 theme bonds 1303:1307 arg1 reactivity 1274:1283 the reactivity 1270:1283 the reactivity of the two double bonds of the allene towards the [2+2+2] cycloaddition reaction 1270:1364 This mechanistic study rationalizes the order in which the unsaturations take part in the catalytic cycle, the reactivity of the two double bonds of the allene towards the [2+2+2] cycloaddition reaction, and the diastereoselectivity of the reaction. 24615797 0 50 theme linear 59:64 arg1 substrates 88:97 linear allene-ene/yne-allene substrates 59:97 linear allene-ene/yne-allene substrates 59:97 Stereoselective rhodium-catalysed [2+2+2] cycloaddition of linear allene-ene/yne-allene substrates: reactivity and theoretical mechanistic studies. 24615797 0 51 dep cycloaddition 42:54 arg1 reactivity 100:109 reactivity 100:109 reactivity 100:109 Stereoselective rhodium-catalysed [2+2+2] cycloaddition of linear allene-ene/yne-allene substrates: reactivity and theoretical mechanistic studies. 24615797 0 51 dep cycloaddition 42:54 arg1 studies 139:145 theoretical mechanistic studies 115:145 theoretical mechanistic studies 115:145 Stereoselective rhodium-catalysed [2+2+2] cycloaddition of linear allene-ene/yne-allene substrates: reactivity and theoretical mechanistic studies. 24615797 5 52 theme therefore 846:854 arg1 reaction 800:807 a regioselective reaction 783:807 a regioselective reaction of the inner allene double bond and, therefore, feature an exocyclic diene motif 783:888 All cycloadducts were formed by a regioselective reaction of the inner allene double bond and, therefore, feature an exocyclic diene motif. 24615797 7 53 theme cycloaddition 1065:1077 arg1 reactions 1079:1087 [2+2+2] cycloaddition reactions 1057:1087 [2+2+2] cycloaddition reactions 1057:1087 The reactivity of the allenes on [2+2+2] cycloaddition reactions was studied for the first time by density functional theory calculations. 24615797 4 54 theme diastereoselective 724:741 arg1 manner 743:748 a diastereoselective manner 722:748 a diastereoselective manner 722:748 The reaction of substrates 3 and 7, which bear a triple bond in the central position, gave a tricyclic structure with a cyclohexenic ring core, again in a diastereoselective manner. 24615797 8 55 theme reaction 1403:1410 arg1 part 1241:1244 part 1241:1244 part in the catalytic cycle 1241:1267 This mechanistic study rationalizes the order in which the unsaturations take part in the catalytic cycle, the reactivity of the two double bonds of the allene towards the [2+2+2] cycloaddition reaction, and the diastereoselectivity of the reaction. 24615797 8 55 theme reaction 1403:1410 arg1 diastereoselectivity 1375:1394 the diastereoselectivity 1371:1394 the diastereoselectivity of the reaction 1371:1410 This mechanistic study rationalizes the order in which the unsaturations take part in the catalytic cycle, the reactivity of the two double bonds of the allene towards the [2+2+2] cycloaddition reaction, and the diastereoselectivity of the reaction. 24615797 8 55 theme reaction 1403:1410 arg1 reactivity 1274:1283 the reactivity 1270:1283 the reactivity of the two double bonds of the allene towards the [2+2+2] cycloaddition reaction 1270:1364 This mechanistic study rationalizes the order in which the unsaturations take part in the catalytic cycle, the reactivity of the two double bonds of the allene towards the [2+2+2] cycloaddition reaction, and the diastereoselectivity of the reaction. 24615797 4 56 theme tricyclic 662:670 arg1 structure 672:680 a tricyclic structure 660:680 a tricyclic structure 660:680 The reaction of substrates 3 and 7, which bear a triple bond in the central position, gave a tricyclic structure with a cyclohexenic ring core, again in a diastereoselective manner. 24615797 4 57 theme cyclohexenic 689:700 arg1 core 707:710 a cyclohexenic ring core 687:710 a cyclohexenic ring core 687:710 The reaction of substrates 3 and 7, which bear a triple bond in the central position, gave a tricyclic structure with a cyclohexenic ring core, again in a diastereoselective manner. 24615797 3 58 theme contiguous 500:509 arg1 centres 523:529 four contiguous stereogenic centres 495:529 four contiguous stereogenic centres 495:529 Substrates 2 and 5, which bear a double bond in the central position, gave a tricyclic structure in a reaction in which four contiguous stereogenic centres were formed as a single diastereomer. 24615797 3 58 theme contiguous 500:509 arg1 diastereomer 555:566 a single diastereomer 546:566 a single diastereomer 546:566 Substrates 2 and 5, which bear a double bond in the central position, gave a tricyclic structure in a reaction in which four contiguous stereogenic centres were formed as a single diastereomer. 24615797 4 59 contain bear 611:614 arg2 bond 625:628 a triple bond 616:628 a triple bond in the central position 616:652 The reaction of substrates 3 and 7, which bear a triple bond in the central position, gave a tricyclic structure with a cyclohexenic ring core, again in a diastereoselective manner. 24615797 4 59 contain bear 611:614 arg1 reaction 573:580 The reaction 569:580 The reaction 569:580 The reaction of substrates 3 and 7, which bear a triple bond in the central position, gave a tricyclic structure with a cyclohexenic ring core, again in a diastereoselective manner. 24615797 2 60 theme [2+2+2 277:282 arg1 reaction 299:306 The [2+2+2] cycloaddition reaction 273:306 The [2+2+2] cycloaddition reaction catalysed by the Wilkinson catalyst [RhCl(PPh3 )3 ] 273:358 The [2+2+2] cycloaddition reaction catalysed by the Wilkinson catalyst [RhCl(PPh3 )3 ] was evaluated. 24615797 3 61 theme tricyclic 452:460 arg1 structure 462:470 a tricyclic structure 450:470 a tricyclic structure 450:470 Substrates 2 and 5, which bear a double bond in the central position, gave a tricyclic structure in a reaction in which four contiguous stereogenic centres were formed as a single diastereomer. 24615797 8 62 theme catalytic 1253:1261 arg1 cycle 1263:1267 the catalytic cycle 1249:1267 the catalytic cycle 1249:1267 This mechanistic study rationalizes the order in which the unsaturations take part in the catalytic cycle, the reactivity of the two double bonds of the allene towards the [2+2+2] cycloaddition reaction, and the diastereoselectivity of the reaction. 24615797 5 63 theme regioselective 785:798 arg1 reaction 800:807 a regioselective reaction 783:807 a regioselective reaction of the inner allene double bond and, therefore, feature an exocyclic diene motif 783:888 All cycloadducts were formed by a regioselective reaction of the inner allene double bond and, therefore, feature an exocyclic diene motif. 24615797 3 64 from bond 415:418 arg1 position 435:442 the central position 423:442 the central position 423:442 Substrates 2 and 5, which bear a double bond in the central position, gave a tricyclic structure in a reaction in which four contiguous stereogenic centres were formed as a single diastereomer. 24615797 5 65 theme allene 822:827 arg1 bond 836:839 the inner allene double bond 812:839 the inner allene double bond 812:839 All cycloadducts were formed by a regioselective reaction of the inner allene double bond and, therefore, feature an exocyclic diene motif. 24615797 8 66 theme allene 1316:1321 arg1 bonds 1303:1307 the two double bonds 1288:1307 the two double bonds of the allene towards the [2+2+2] cycloaddition reaction 1288:1364 This mechanistic study rationalizes the order in which the unsaturations take part in the catalytic cycle, the reactivity of the two double bonds of the allene towards the [2+2+2] cycloaddition reaction, and the diastereoselectivity of the reaction. 24615797 0 67 theme substrates 88:97 arg1 cycloaddition 42:54 Stereoselective rhodium-catalysed [2+2+2] cycloaddition 0:54 Stereoselective rhodium-catalysed [2+2+2] cycloaddition of linear allene-ene/yne-allene substrates: reactivity and theoretical mechanistic studies. 0:146 Stereoselective rhodium-catalysed [2+2+2] cycloaddition of linear allene-ene/yne-allene substrates: reactivity and theoretical mechanistic studies. 24615797 7 68 from reactions 1079:1087 arg1 reactivity 1028:1037 The reactivity 1024:1037 The reactivity of the allenes on [2+2+2] cycloaddition reactions 1024:1087 The reactivity of the allenes on [2+2+2] cycloaddition reactions was studied for the first time by density functional theory calculations. 24615797 0 69 theme [2+2+2 34:39 arg1 cycloaddition 42:54 Stereoselective rhodium-catalysed [2+2+2] cycloaddition 0:54 Stereoselective rhodium-catalysed [2+2+2] cycloaddition of linear allene-ene/yne-allene substrates: reactivity and theoretical mechanistic studies. 0:146 Stereoselective rhodium-catalysed [2+2+2] cycloaddition of linear allene-ene/yne-allene substrates: reactivity and theoretical mechanistic studies. 24615797 5 70 theme double 829:834 arg1 bond 836:839 the inner allene double bond 812:839 the inner allene double bond 812:839 All cycloadducts were formed by a regioselective reaction of the inner allene double bond and, therefore, feature an exocyclic diene motif. 24615797 4 71 theme substrates 585:594 arg1 reaction 573:580 The reaction 569:580 The reaction 569:580 The reaction of substrates 3 and 7, which bear a triple bond in the central position, gave a tricyclic structure with a cyclohexenic ring core, again in a diastereoselective manner. 24526360 6 0 theme recombinant 823:833 arg1 proteins 835:842 some recombinant proteins 818:842 some recombinant proteins 818:842 As a consequence, nondesirable proteolysis of some recombinant proteins may occur, with the specific cleavage being dependent on the class of protease involved. 24526360 10 1 theme therapeutic 1500:1510 arg1 proteins 1512:1519 recombinant therapeutic proteins 1488:1519 recombinant therapeutic proteins with their intact native sequences 1488:1554 As such, this understanding of DPP activity enhances the utility of the P. pastoris expression system, thus facilitating the production of recombinant therapeutic proteins with their intact native sequences. 24526360 7 2 theme enzymes 993:999 arg1 aminopeptidases 944:958 Dipeptidyl aminopeptidases 933:958 Dipeptidyl aminopeptidases (DPP) 933:964 Dipeptidyl aminopeptidases (DPP) are a class of proteolytic enzymes which remove a two-amino acid peptide from the N-terminus of a protein. 24526360 7 2 theme enzymes 993:999 arg1 class 972:976 a class 970:976 a class of proteolytic enzymes which remove a two-amino acid peptide from the N-terminus of a protein 970:1070 Dipeptidyl aminopeptidases (DPP) are a class of proteolytic enzymes which remove a two-amino acid peptide from the N-terminus of a protein. 24526360 1 3 theme proteins 171:178 arg1 generation 145:154 the generation 141:154 the generation of recombinant proteins 141:178 Yeast are important production platforms for the generation of recombinant proteins. 24526360 10 4 theme recombinant 1488:1498 arg1 proteins 1512:1519 recombinant therapeutic proteins 1488:1519 recombinant therapeutic proteins with their intact native sequences 1488:1554 As such, this understanding of DPP activity enhances the utility of the P. pastoris expression system, thus facilitating the production of recombinant therapeutic proteins with their intact native sequences. 24526360 4 5 theme Recent 420:425 arg1 advances 427:434 Recent advances 420:434 Recent advances in the glycoengineering of this strain 420:473 Recent advances in the glycoengineering of this strain offer the potential to produce therapeutic glycoproteins with sialylated human-like N- and O-linked glycans. 24526360 6 6 theme specific 864:871 arg1 cleavage 873:880 the specific cleavage 860:880 the specific cleavage 860:880 As a consequence, nondesirable proteolysis of some recombinant proteins may occur, with the specific cleavage being dependent on the class of protease involved. 24526360 6 6 theme specific 864:871 arg1 dependent 888:896 dependent 888:896 dependent 888:896 As a consequence, nondesirable proteolysis of some recombinant proteins may occur, with the specific cleavage being dependent on the class of protease involved. 24526360 0 7 from Elimination 0:10 arg1 pastoris 51:58 Pichia pastoris 44:58 Pichia pastoris 44:58 Elimination of diaminopeptidase activity in Pichia pastoris for therapeutic protein production. 24526360 5 8 theme numerous 636:643 arg1 proteases 645:653 numerous proteases 636:653 numerous proteases 636:653 However, like higher eukaryotes, yeast also express numerous proteases, many of which are either localized to the secretory pathway or pass through it en route to their final destination. 24526360 10 9 theme native 1539:1544 arg1 sequences 1546:1554 their intact native sequences 1526:1554 their intact native sequences 1526:1554 As such, this understanding of DPP activity enhances the utility of the P. pastoris expression system, thus facilitating the production of recombinant therapeutic proteins with their intact native sequences. 24526360 9 10 theme other 1278:1282 arg1 proteins 1284:1291 other proteins 1278:1291 other proteins 1278:1291 In the current report, we demonstrate that while the knockout of STE13 alone may protect certain proteins from N-terminal clipping, other proteins may require the double knockout of both STE13 and DAP2. 24526360 4 11 from advances 427:434 arg1 glycoengineering 443:458 the glycoengineering 439:458 the glycoengineering of this strain 439:473 Recent advances in the glycoengineering of this strain offer the potential to produce therapeutic glycoproteins with sialylated human-like N- and O-linked glycans. 24526360 5 12 theme proteases 645:653 arg1 many 656:659 many 656:659 many 656:659 However, like higher eukaryotes, yeast also express numerous proteases, many of which are either localized to the secretory pathway or pass through it en route to their final destination. 24526360 5 12 theme proteases 645:653 arg1 proteases 645:653 numerous proteases 636:653 numerous proteases 636:653 However, like higher eukaryotes, yeast also express numerous proteases, many of which are either localized to the secretory pathway or pass through it en route to their final destination. 24526360 2 13 theme glycosylation 294:306 arg1 profile 308:314 their glycosylation profile 288:314 their glycosylation profile with that of higher eukaryotes 288:345 Nonetheless, their use has been restricted in the production of therapeutic proteins due to differences in their glycosylation profile with that of higher eukaryotes. 24526360 3 14 theme strain 358:363 arg1 organism 410:417 an industrially important organism 384:417 an industrially important organism 384:417 The yeast strain Pichia pastoris is an industrially important organism. 24526360 3 14 theme strain 358:363 arg1 pastoris 372:379 The yeast strain Pichia pastoris 348:379 The yeast strain Pichia pastoris 348:379 The yeast strain Pichia pastoris is an industrially important organism. 24526360 10 15 with proteins 1512:1519 arg1 sequences 1546:1554 their intact native sequences 1526:1554 their intact native sequences 1526:1554 As such, this understanding of DPP activity enhances the utility of the P. pastoris expression system, thus facilitating the production of recombinant therapeutic proteins with their intact native sequences. 24526360 10 16 theme proteins 1512:1519 arg1 production 1474:1483 the production 1470:1483 the production of recombinant therapeutic proteins with their intact native sequences 1470:1554 As such, this understanding of DPP activity enhances the utility of the P. pastoris expression system, thus facilitating the production of recombinant therapeutic proteins with their intact native sequences. 24526360 4 17 gly sialylated 537:546 arg1 N- 559:560 sialylated human-like N- 537:560 sialylated human-like N- 537:560 Recent advances in the glycoengineering of this strain offer the potential to produce therapeutic glycoproteins with sialylated human-like N- and O-linked glycans. 24526360 3 18 theme Pichia 365:370 arg1 organism 410:417 an industrially important organism 384:417 an industrially important organism 384:417 The yeast strain Pichia pastoris is an industrially important organism. 24526360 3 18 theme Pichia 365:370 arg1 pastoris 372:379 The yeast strain Pichia pastoris 348:379 The yeast strain Pichia pastoris 348:379 The yeast strain Pichia pastoris is an industrially important organism. 24526360 4 19 link O-linked 566:573 arg1 glycans 575:581 O-linked glycans 566:581 O-linked glycans 566:581 Recent advances in the glycoengineering of this strain offer the potential to produce therapeutic glycoproteins with sialylated human-like N- and O-linked glycans. 24526360 10 20 theme P. 1421:1422 arg1 system 1444:1449 the P. pastoris expression system 1417:1449 the P. pastoris expression system 1417:1449 As such, this understanding of DPP activity enhances the utility of the P. pastoris expression system, thus facilitating the production of recombinant therapeutic proteins with their intact native sequences. 24526360 10 21 theme expression 1433:1442 arg1 system 1444:1449 the P. pastoris expression system 1417:1449 the P. pastoris expression system 1417:1449 As such, this understanding of DPP activity enhances the utility of the P. pastoris expression system, thus facilitating the production of recombinant therapeutic proteins with their intact native sequences. 24526360 5 22 theme final 753:757 arg1 destination 759:769 their final destination 747:769 their final destination 747:769 However, like higher eukaryotes, yeast also express numerous proteases, many of which are either localized to the secretory pathway or pass through it en route to their final destination. 24526360 3 23 theme important 400:408 arg1 organism 410:417 an industrially important organism 384:417 an industrially important organism 384:417 The yeast strain Pichia pastoris is an industrially important organism. 24526360 3 23 theme important 400:408 arg1 pastoris 372:379 The yeast strain Pichia pastoris 348:379 The yeast strain Pichia pastoris 348:379 The yeast strain Pichia pastoris is an industrially important organism. 24526360 4 24 theme therapeutic 506:516 arg1 glycoproteins 518:530 therapeutic glycoproteins 506:530 therapeutic glycoproteins with sialylated human-like N- and O-linked glycans 506:581 Recent advances in the glycoengineering of this strain offer the potential to produce therapeutic glycoproteins with sialylated human-like N- and O-linked glycans. 24526360 2 25 theme higher 329:334 arg1 eukaryotes 336:345 higher eukaryotes 329:345 higher eukaryotes 329:345 Nonetheless, their use has been restricted in the production of therapeutic proteins due to differences in their glycosylation profile with that of higher eukaryotes. 24526360 6 26 theme proteins 835:842 arg1 proteolysis 803:813 nondesirable proteolysis 790:813 nondesirable proteolysis of some recombinant proteins 790:842 As a consequence, nondesirable proteolysis of some recombinant proteins may occur, with the specific cleavage being dependent on the class of protease involved. 24526360 6 27 theme nondesirable 790:801 arg1 proteolysis 803:813 nondesirable proteolysis 790:813 nondesirable proteolysis of some recombinant proteins 790:842 As a consequence, nondesirable proteolysis of some recombinant proteins may occur, with the specific cleavage being dependent on the class of protease involved. 24526360 0 28 theme activity 32:39 arg1 Elimination 0:10 Elimination 0:10 Elimination of diaminopeptidase activity in Pichia pastoris for therapeutic protein production. 0:94 Elimination of diaminopeptidase activity in Pichia pastoris for therapeutic protein production. 24526360 1 29 theme important 106:114 arg1 platforms 127:135 important production platforms 106:135 important production platforms for the generation of recombinant proteins 106:178 Yeast are important production platforms for the generation of recombinant proteins. 24526360 1 29 theme important 106:114 arg1 Yeast 96:100 Yeast 96:100 Yeast 96:100 Yeast are important production platforms for the generation of recombinant proteins. 24526360 9 30 theme current 1153:1159 arg1 report 1161:1166 the current report 1149:1166 the current report 1149:1166 In the current report, we demonstrate that while the knockout of STE13 alone may protect certain proteins from N-terminal clipping, other proteins may require the double knockout of both STE13 and DAP2. 24526360 6 31 theme protease 914:921 arg1 class 905:909 the class 901:909 the class of protease involved 901:930 As a consequence, nondesirable proteolysis of some recombinant proteins may occur, with the specific cleavage being dependent on the class of protease involved. 24526360 0 32 theme diaminopeptidase 15:30 arg1 activity 32:39 diaminopeptidase activity 15:39 diaminopeptidase activity 15:39 Elimination of diaminopeptidase activity in Pichia pastoris for therapeutic protein production. 24526360 1 33 theme production 116:125 arg1 platforms 127:135 important production platforms 106:135 important production platforms for the generation of recombinant proteins 106:178 Yeast are important production platforms for the generation of recombinant proteins. 24526360 1 33 theme production 116:125 arg1 Yeast 96:100 Yeast 96:100 Yeast 96:100 Yeast are important production platforms for the generation of recombinant proteins. 24526360 2 34 from differences 273:283 arg1 profile 308:314 their glycosylation profile 288:314 their glycosylation profile with that of higher eukaryotes 288:345 Nonetheless, their use has been restricted in the production of therapeutic proteins due to differences in their glycosylation profile with that of higher eukaryotes. 24526360 0 35 theme Pichia 44:49 arg1 pastoris 51:58 Pichia pastoris 44:58 Pichia pastoris 44:58 Elimination of diaminopeptidase activity in Pichia pastoris for therapeutic protein production. 24526360 10 36 theme system 1444:1449 arg1 utility 1406:1412 the utility 1402:1412 the utility of the P. pastoris expression system 1402:1449 As such, this understanding of DPP activity enhances the utility of the P. pastoris expression system, thus facilitating the production of recombinant therapeutic proteins with their intact native sequences. 24526360 4 37 theme strain 468:473 arg1 glycoengineering 443:458 the glycoengineering 439:458 the glycoengineering of this strain 439:473 Recent advances in the glycoengineering of this strain offer the potential to produce therapeutic glycoproteins with sialylated human-like N- and O-linked glycans. 24526360 2 38 theme therapeutic 245:255 arg1 proteins 257:264 therapeutic proteins 245:264 therapeutic proteins due to differences in their glycosylation profile with that of higher eukaryotes 245:345 Nonetheless, their use has been restricted in the production of therapeutic proteins due to differences in their glycosylation profile with that of higher eukaryotes. 24526360 4 39 gly glycoproteins 518:530 arg1 glycoproteins 518:530 therapeutic glycoproteins 506:530 therapeutic glycoproteins with sialylated human-like N- and O-linked glycans 506:581 Recent advances in the glycoengineering of this strain offer the potential to produce therapeutic glycoproteins with sialylated human-like N- and O-linked glycans. 24526360 4 40 theme O-linked 566:573 arg1 glycans 575:581 O-linked glycans 566:581 O-linked glycans 566:581 Recent advances in the glycoengineering of this strain offer the potential to produce therapeutic glycoproteins with sialylated human-like N- and O-linked glycans. 24526360 7 41 theme protein 1064:1070 arg1 N-terminus 1048:1057 the N-terminus 1044:1057 the N-terminus of a protein 1044:1070 Dipeptidyl aminopeptidases (DPP) are a class of proteolytic enzymes which remove a two-amino acid peptide from the N-terminus of a protein. 24526360 9 42 theme STE13 1211:1215 arg1 knockout 1199:1206 knockout 1199:1206 knockout 1199:1206 In the current report, we demonstrate that while the knockout of STE13 alone may protect certain proteins from N-terminal clipping, other proteins may require the double knockout of both STE13 and DAP2. 24526360 7 43 theme acid 1026:1029 arg1 peptide 1031:1037 a two-amino acid peptide 1014:1037 a two-amino acid peptide 1014:1037 Dipeptidyl aminopeptidases (DPP) are a class of proteolytic enzymes which remove a two-amino acid peptide from the N-terminus of a protein. 24526360 10 44 dep P. 1421:1422 arg1 pastoris 1424:1431 pastoris 1424:1431 pastoris 1424:1431 As such, this understanding of DPP activity enhances the utility of the P. pastoris expression system, thus facilitating the production of recombinant therapeutic proteins with their intact native sequences. 24526360 10 45 theme activity 1384:1391 arg1 understanding 1363:1375 this understanding 1358:1375 this understanding of DPP activity 1358:1391 As such, this understanding of DPP activity enhances the utility of the P. pastoris expression system, thus facilitating the production of recombinant therapeutic proteins with their intact native sequences. 24526360 9 46 theme STE13 1333:1337 arg1 knockout 1316:1323 knockout 1316:1323 knockout 1316:1323 In the current report, we demonstrate that while the knockout of STE13 alone may protect certain proteins from N-terminal clipping, other proteins may require the double knockout of both STE13 and DAP2. 24526360 5 47 theme secretory 698:706 arg1 pathway 708:714 the secretory pathway 694:714 the secretory pathway 694:714 However, like higher eukaryotes, yeast also express numerous proteases, many of which are either localized to the secretory pathway or pass through it en route to their final destination. 24526360 0 48 theme therapeutic 64:74 arg1 production 84:93 therapeutic protein production 64:93 therapeutic protein production 64:93 Elimination of diaminopeptidase activity in Pichia pastoris for therapeutic protein production. 24526360 4 49 theme human-like 548:557 arg1 N- 559:560 sialylated human-like N- 537:560 sialylated human-like N- 537:560 Recent advances in the glycoengineering of this strain offer the potential to produce therapeutic glycoproteins with sialylated human-like N- and O-linked glycans. 24526360 8 50 theme such 1093:1096 arg1 enzymes 1098:1104 two such enzymes 1089:1104 two such enzymes 1089:1104 In P. pastoris, two such enzymes have been identified, Ste13p and Dap2p. 24526360 9 51 theme DAP2 1343:1346 arg1 knockout 1316:1323 knockout 1316:1323 knockout 1316:1323 In the current report, we demonstrate that while the knockout of STE13 alone may protect certain proteins from N-terminal clipping, other proteins may require the double knockout of both STE13 and DAP2. 24526360 10 52 theme DPP 1380:1382 arg1 activity 1384:1391 DPP activity 1380:1391 DPP activity 1380:1391 As such, this understanding of DPP activity enhances the utility of the P. pastoris expression system, thus facilitating the production of recombinant therapeutic proteins with their intact native sequences. 24526360 5 53 theme higher 598:603 arg1 eukaryotes 605:614 higher eukaryotes 598:614 higher eukaryotes 598:614 However, like higher eukaryotes, yeast also express numerous proteases, many of which are either localized to the secretory pathway or pass through it en route to their final destination. 24526360 7 54 theme Dipeptidyl 933:942 arg1 DPP 961:963 DPP 961:963 DPP 961:963 Dipeptidyl aminopeptidases (DPP) are a class of proteolytic enzymes which remove a two-amino acid peptide from the N-terminus of a protein. 24526360 7 54 theme Dipeptidyl 933:942 arg1 aminopeptidases 944:958 Dipeptidyl aminopeptidases 933:958 Dipeptidyl aminopeptidases (DPP) 933:964 Dipeptidyl aminopeptidases (DPP) are a class of proteolytic enzymes which remove a two-amino acid peptide from the N-terminus of a protein. 24526360 7 54 theme Dipeptidyl 933:942 arg1 class 972:976 a class 970:976 a class of proteolytic enzymes which remove a two-amino acid peptide from the N-terminus of a protein 970:1070 Dipeptidyl aminopeptidases (DPP) are a class of proteolytic enzymes which remove a two-amino acid peptide from the N-terminus of a protein. 24526360 7 55 theme two-amino 1016:1024 arg1 peptide 1031:1037 a two-amino acid peptide 1014:1037 a two-amino acid peptide 1014:1037 Dipeptidyl aminopeptidases (DPP) are a class of proteolytic enzymes which remove a two-amino acid peptide from the N-terminus of a protein. 24526360 9 56 theme certain 1235:1241 arg1 proteins 1243:1250 certain proteins 1235:1250 certain proteins 1235:1250 In the current report, we demonstrate that while the knockout of STE13 alone may protect certain proteins from N-terminal clipping, other proteins may require the double knockout of both STE13 and DAP2. 24526360 10 57 theme intact 1532:1537 arg1 sequences 1546:1554 their intact native sequences 1526:1554 their intact native sequences 1526:1554 As such, this understanding of DPP activity enhances the utility of the P. pastoris expression system, thus facilitating the production of recombinant therapeutic proteins with their intact native sequences. 24526360 0 58 theme protein 76:82 arg1 production 84:93 therapeutic protein production 64:93 therapeutic protein production 64:93 Elimination of diaminopeptidase activity in Pichia pastoris for therapeutic protein production. 24526360 2 59 theme due 266:268 arg1 proteins 257:264 therapeutic proteins 245:264 therapeutic proteins due to differences in their glycosylation profile with that of higher eukaryotes 245:345 Nonetheless, their use has been restricted in the production of therapeutic proteins due to differences in their glycosylation profile with that of higher eukaryotes. 24526360 4 60 with glycoproteins 518:530 arg1 glycans 575:581 O-linked glycans 566:581 O-linked glycans 566:581 Recent advances in the glycoengineering of this strain offer the potential to produce therapeutic glycoproteins with sialylated human-like N- and O-linked glycans. 24526360 4 60 with glycoproteins 518:530 arg1 N- 559:560 sialylated human-like N- 537:560 sialylated human-like N- 537:560 Recent advances in the glycoengineering of this strain offer the potential to produce therapeutic glycoproteins with sialylated human-like N- and O-linked glycans. 24526360 2 61 with profile 308:314 arg1 that 321:324 that 321:324 that 321:324 Nonetheless, their use has been restricted in the production of therapeutic proteins due to differences in their glycosylation profile with that of higher eukaryotes. 24526360 3 62 theme yeast 352:356 arg1 organism 410:417 an industrially important organism 384:417 an industrially important organism 384:417 The yeast strain Pichia pastoris is an industrially important organism. 24526360 3 62 theme yeast 352:356 arg1 pastoris 372:379 The yeast strain Pichia pastoris 348:379 The yeast strain Pichia pastoris 348:379 The yeast strain Pichia pastoris is an industrially important organism. 24526360 4 63 theme sialylated 537:546 arg1 N- 559:560 sialylated human-like N- 537:560 sialylated human-like N- 537:560 Recent advances in the glycoengineering of this strain offer the potential to produce therapeutic glycoproteins with sialylated human-like N- and O-linked glycans. 24526360 2 64 theme proteins 257:264 arg1 production 231:240 the production 227:240 the production of therapeutic proteins due to differences in their glycosylation profile with that of higher eukaryotes 227:345 Nonetheless, their use has been restricted in the production of therapeutic proteins due to differences in their glycosylation profile with that of higher eukaryotes. 24526360 7 65 theme proteolytic 981:991 arg1 enzymes 993:999 proteolytic enzymes 981:999 proteolytic enzymes 981:999 Dipeptidyl aminopeptidases (DPP) are a class of proteolytic enzymes which remove a two-amino acid peptide from the N-terminus of a protein. 24526360 1 66 theme recombinant 159:169 arg1 proteins 171:178 recombinant proteins 159:178 recombinant proteins 159:178 Yeast are important production platforms for the generation of recombinant proteins. 27131894 1 0 from screening 191:199 arg1 attributes 256:265 productivity and protein quality attributes 223:265 productivity and protein quality attributes of mammalian cell cultures 223:292 Recent advances in miniaturized cell culture systems have facilitated the screening of media additives on productivity and protein quality attributes of mammalian cell cultures. 27131894 4 1 theme media 768:772 arg1 Supplementation 741:755 Supplementation 741:755 Supplementation of various media 741:772 Supplementation of various media additives significantly altered the intracellular nucleotides and nucleotide sugars that are inextricably linked to the process of glycosylation. 27131894 1 2 theme mammalian 270:278 arg1 cultures 285:292 mammalian cell cultures 270:292 mammalian cell cultures 270:292 Recent advances in miniaturized cell culture systems have facilitated the screening of media additives on productivity and protein quality attributes of mammalian cell cultures. 27131894 6 3 theme intracellular 1229:1241 arg1 components 1243:1252 intracellular components 1229:1252 intracellular components 1229:1252 In contrast, manganese and asparagine supplementation altered the glycan profiles without affecting intracellular components. 27131894 3 4 theme micro-scale 541:551 arg1 system 564:569 a micro-scale bioreactor system 539:569 a micro-scale bioreactor system 539:569 In this work, time profiling of intracellular nucleotides and nucleotide sugars of CHO-S cell fed-batch processes in a micro-scale bioreactor system was carried out using a recently developed high-throughput method based on matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry (TOF-MS). 27131894 1 5 theme cell 280:283 arg1 cultures 285:292 mammalian cell cultures 270:292 mammalian cell cultures 270:292 Recent advances in miniaturized cell culture systems have facilitated the screening of media additives on productivity and protein quality attributes of mammalian cell cultures. 27131894 3 6 theme bioreactor 553:562 arg1 system 564:569 a micro-scale bioreactor system 539:569 a micro-scale bioreactor system 539:569 In this work, time profiling of intracellular nucleotides and nucleotide sugars of CHO-S cell fed-batch processes in a micro-scale bioreactor system was carried out using a recently developed high-throughput method based on matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry (TOF-MS). 27131894 3 7 theme intracellular 454:466 arg1 nucleotides 468:478 intracellular nucleotides 454:478 intracellular nucleotides 454:478 In this work, time profiling of intracellular nucleotides and nucleotide sugars of CHO-S cell fed-batch processes in a micro-scale bioreactor system was carried out using a recently developed high-throughput method based on matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry (TOF-MS). 27131894 1 8 theme cultures 285:292 arg1 attributes 256:265 productivity and protein quality attributes 223:265 productivity and protein quality attributes of mammalian cell cultures 223:292 Recent advances in miniaturized cell culture systems have facilitated the screening of media additives on productivity and protein quality attributes of mammalian cell cultures. 27131894 0 9 theme antibody 91:98 arg1 N-glycosylation 100:114 antibody N-glycosylation 91:114 antibody N-glycosylation 91:114 High-throughput profiling of nucleotides and nucleotide sugars to evaluate their impact on antibody N-glycosylation. 27131894 5 10 theme final 1069:1073 arg1 patterns 1089:1096 the final glycosylation patterns 1065:1096 the final glycosylation patterns 1065:1096 The results revealed that UDP-Gal synthesis appeared to be particularly limiting whereas the impact of elevated UDP-GlcNAc and GDP-Fuc levels on the final glycosylation patterns was only marginally important. 27131894 5 11 theme UDP-GlcNAc 1032:1041 arg1 levels 1055:1060 elevated UDP-GlcNAc and GDP-Fuc levels 1023:1060 elevated UDP-GlcNAc and GDP-Fuc levels 1023:1060 The results revealed that UDP-Gal synthesis appeared to be particularly limiting whereas the impact of elevated UDP-GlcNAc and GDP-Fuc levels on the final glycosylation patterns was only marginally important. 27131894 2 12 theme intracellular 304:316 arg1 components 318:327 intracellular components 304:327 intracellular components 304:327 However, intracellular components are not routinely measured due to the limited throughput of available analytical techniques. 27131894 3 13 theme fed-batch 516:524 arg1 processes 526:534 CHO-S cell fed-batch processes 505:534 CHO-S cell fed-batch processes in a micro-scale bioreactor system 505:569 In this work, time profiling of intracellular nucleotides and nucleotide sugars of CHO-S cell fed-batch processes in a micro-scale bioreactor system was carried out using a recently developed high-throughput method based on matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry (TOF-MS). 27131894 4 14 theme various 760:766 arg1 media 768:772 various media 760:772 various media 760:772 Supplementation of various media additives significantly altered the intracellular nucleotides and nucleotide sugars that are inextricably linked to the process of glycosylation. 27131894 3 15 theme processes 526:534 arg1 nucleotides 468:478 intracellular nucleotides 454:478 intracellular nucleotides 454:478 In this work, time profiling of intracellular nucleotides and nucleotide sugars of CHO-S cell fed-batch processes in a micro-scale bioreactor system was carried out using a recently developed high-throughput method based on matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry (TOF-MS). 27131894 3 15 theme processes 526:534 arg1 sugars 495:500 nucleotide sugars 484:500 nucleotide sugars 484:500 In this work, time profiling of intracellular nucleotides and nucleotide sugars of CHO-S cell fed-batch processes in a micro-scale bioreactor system was carried out using a recently developed high-throughput method based on matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry (TOF-MS). 27131894 7 16 theme analytical 1321:1330 arg1 techniques 1332:1341 high-throughput analytical techniques 1305:1341 high-throughput analytical techniques 1305:1341 The combination of miniaturized cell cultures and high-throughput analytical techniques serves therefore as a useful tool for future quality driven media optimization studies. 27131894 3 17 theme CHO-S 505:509 arg1 processes 526:534 CHO-S cell fed-batch processes 505:534 CHO-S cell fed-batch processes in a micro-scale bioreactor system 505:569 In this work, time profiling of intracellular nucleotides and nucleotide sugars of CHO-S cell fed-batch processes in a micro-scale bioreactor system was carried out using a recently developed high-throughput method based on matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry (TOF-MS). 27131894 5 18 theme glycosylation 1075:1087 arg1 patterns 1089:1096 the final glycosylation patterns 1065:1096 the final glycosylation patterns 1065:1096 The results revealed that UDP-Gal synthesis appeared to be particularly limiting whereas the impact of elevated UDP-GlcNAc and GDP-Fuc levels on the final glycosylation patterns was only marginally important. 27131894 5 19 theme elevated 1023:1030 arg1 levels 1055:1060 elevated UDP-GlcNAc and GDP-Fuc levels 1023:1060 elevated UDP-GlcNAc and GDP-Fuc levels 1023:1060 The results revealed that UDP-Gal synthesis appeared to be particularly limiting whereas the impact of elevated UDP-GlcNAc and GDP-Fuc levels on the final glycosylation patterns was only marginally important. 27131894 3 20 theme nucleotide 484:493 arg1 sugars 495:500 nucleotide sugars 484:500 nucleotide sugars 484:500 In this work, time profiling of intracellular nucleotides and nucleotide sugars of CHO-S cell fed-batch processes in a micro-scale bioreactor system was carried out using a recently developed high-throughput method based on matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry (TOF-MS). 27131894 5 21 from impact 1013:1018 arg1 patterns 1089:1096 the final glycosylation patterns 1065:1096 the final glycosylation patterns 1065:1096 The results revealed that UDP-Gal synthesis appeared to be particularly limiting whereas the impact of elevated UDP-GlcNAc and GDP-Fuc levels on the final glycosylation patterns was only marginally important. 27131894 3 22 theme time 436:439 arg1 profiling 441:449 time profiling 436:449 time profiling of intracellular nucleotides and nucleotide sugars of CHO-S cell fed-batch processes in a micro-scale bioreactor system 436:569 In this work, time profiling of intracellular nucleotides and nucleotide sugars of CHO-S cell fed-batch processes in a micro-scale bioreactor system was carried out using a recently developed high-throughput method based on matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry (TOF-MS). 27131894 6 23 theme glycan 1195:1200 arg1 profiles 1202:1209 the glycan profiles 1191:1209 the glycan profiles 1191:1209 In contrast, manganese and asparagine supplementation altered the glycan profiles without affecting intracellular components. 27131894 7 24 theme techniques 1332:1341 arg1 combination 1259:1269 The combination 1255:1269 The combination of miniaturized cell cultures and high-throughput analytical techniques 1255:1341 The combination of miniaturized cell cultures and high-throughput analytical techniques serves therefore as a useful tool for future quality driven media optimization studies. 27131894 7 24 theme techniques 1332:1341 arg1 tool 1372:1375 a useful tool 1363:1375 a useful tool for future quality driven media optimization studies 1363:1428 The combination of miniaturized cell cultures and high-throughput analytical techniques serves therefore as a useful tool for future quality driven media optimization studies. 27131894 7 25 theme optimization 1409:1420 arg1 studies 1422:1428 future quality driven media optimization studies 1381:1428 future quality driven media optimization studies 1381:1428 The combination of miniaturized cell cultures and high-throughput analytical techniques serves therefore as a useful tool for future quality driven media optimization studies. 27131894 3 26 theme developed 604:612 arg1 method 630:635 a recently developed high-throughput method 593:635 a recently developed high-throughput method based on matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry (TOF-MS) 593:738 In this work, time profiling of intracellular nucleotides and nucleotide sugars of CHO-S cell fed-batch processes in a micro-scale bioreactor system was carried out using a recently developed high-throughput method based on matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry (TOF-MS). 27131894 0 27 theme High-throughput 0:14 arg1 profiling 16:24 High-throughput profiling 0:24 High-throughput profiling of nucleotides and nucleotide sugars 0:61 High-throughput profiling of nucleotides and nucleotide sugars to evaluate their impact on antibody N-glycosylation. 27131894 7 28 theme cultures 1292:1299 arg1 combination 1259:1269 The combination 1255:1269 The combination of miniaturized cell cultures and high-throughput analytical techniques 1255:1341 The combination of miniaturized cell cultures and high-throughput analytical techniques serves therefore as a useful tool for future quality driven media optimization studies. 27131894 7 28 theme cultures 1292:1299 arg1 tool 1372:1375 a useful tool 1363:1375 a useful tool for future quality driven media optimization studies 1363:1428 The combination of miniaturized cell cultures and high-throughput analytical techniques serves therefore as a useful tool for future quality driven media optimization studies. 27131894 1 29 from advances 124:131 arg1 systems 162:168 miniaturized cell culture systems 136:168 miniaturized cell culture systems 136:168 Recent advances in miniaturized cell culture systems have facilitated the screening of media additives on productivity and protein quality attributes of mammalian cell cultures. 27131894 3 30 theme high-throughput 614:628 arg1 method 630:635 a recently developed high-throughput method 593:635 a recently developed high-throughput method based on matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry (TOF-MS) 593:738 In this work, time profiling of intracellular nucleotides and nucleotide sugars of CHO-S cell fed-batch processes in a micro-scale bioreactor system was carried out using a recently developed high-throughput method based on matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry (TOF-MS). 27131894 4 31 dep additives 774:782 arg1 altered 798:804 altered 798:804 additives significantly altered the intracellular nucleotides and nucleotide sugars that are inextricably linked to the process of glycosylation 774:917 Supplementation of various media additives significantly altered the intracellular nucleotides and nucleotide sugars that are inextricably linked to the process of glycosylation. 27131894 2 32 theme techniques 410:419 arg1 throughput 375:384 the limited throughput 363:384 the limited throughput of available analytical techniques 363:419 However, intracellular components are not routinely measured due to the limited throughput of available analytical techniques. 27131894 0 33 theme nucleotides 29:39 arg1 profiling 16:24 High-throughput profiling 0:24 High-throughput profiling of nucleotides and nucleotide sugars 0:61 High-throughput profiling of nucleotides and nucleotide sugars to evaluate their impact on antibody N-glycosylation. 27131894 3 34 from processes 526:534 arg1 system 564:569 a micro-scale bioreactor system 539:569 a micro-scale bioreactor system 539:569 In this work, time profiling of intracellular nucleotides and nucleotide sugars of CHO-S cell fed-batch processes in a micro-scale bioreactor system was carried out using a recently developed high-throughput method based on matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry (TOF-MS). 27131894 3 35 from system 564:569 arg1 nucleotides 468:478 intracellular nucleotides 454:478 intracellular nucleotides 454:478 In this work, time profiling of intracellular nucleotides and nucleotide sugars of CHO-S cell fed-batch processes in a micro-scale bioreactor system was carried out using a recently developed high-throughput method based on matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry (TOF-MS). 27131894 3 35 from system 564:569 arg1 sugars 495:500 nucleotide sugars 484:500 nucleotide sugars 484:500 In this work, time profiling of intracellular nucleotides and nucleotide sugars of CHO-S cell fed-batch processes in a micro-scale bioreactor system was carried out using a recently developed high-throughput method based on matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry (TOF-MS). 27131894 4 36 theme nucleotide 840:849 arg1 sugars 851:856 nucleotide sugars 840:856 nucleotide sugars 840:856 Supplementation of various media additives significantly altered the intracellular nucleotides and nucleotide sugars that are inextricably linked to the process of glycosylation. 27131894 1 37 theme additives 210:218 arg1 screening 191:199 the screening 187:199 the screening of media additives on productivity and protein quality attributes of mammalian cell cultures 187:292 Recent advances in miniaturized cell culture systems have facilitated the screening of media additives on productivity and protein quality attributes of mammalian cell cultures. 27131894 4 38 theme intracellular 810:822 arg1 nucleotides 824:834 intracellular nucleotides 810:834 intracellular nucleotides 810:834 Supplementation of various media additives significantly altered the intracellular nucleotides and nucleotide sugars that are inextricably linked to the process of glycosylation. 27131894 5 39 theme GDP-Fuc 1047:1053 arg1 levels 1055:1060 elevated UDP-GlcNAc and GDP-Fuc levels 1023:1060 elevated UDP-GlcNAc and GDP-Fuc levels 1023:1060 The results revealed that UDP-Gal synthesis appeared to be particularly limiting whereas the impact of elevated UDP-GlcNAc and GDP-Fuc levels on the final glycosylation patterns was only marginally important. 27131894 3 40 theme mass 713:716 arg1 TOF-MS 732:737 TOF-MS 732:737 TOF-MS 732:737 In this work, time profiling of intracellular nucleotides and nucleotide sugars of CHO-S cell fed-batch processes in a micro-scale bioreactor system was carried out using a recently developed high-throughput method based on matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry (TOF-MS). 27131894 3 40 theme mass 713:716 arg1 spectrometry 718:729 matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry 646:729 matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry (TOF-MS) 646:738 In this work, time profiling of intracellular nucleotides and nucleotide sugars of CHO-S cell fed-batch processes in a micro-scale bioreactor system was carried out using a recently developed high-throughput method based on matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry (TOF-MS). 27131894 1 41 theme Recent 117:122 arg1 advances 124:131 Recent advances 117:131 Recent advances in miniaturized cell culture systems 117:168 Recent advances in miniaturized cell culture systems have facilitated the screening of media additives on productivity and protein quality attributes of mammalian cell cultures. 27131894 2 42 theme analytical 399:408 arg1 techniques 410:419 available analytical techniques 389:419 available analytical techniques 389:419 However, intracellular components are not routinely measured due to the limited throughput of available analytical techniques. 27131894 0 43 theme nucleotide 45:54 arg1 sugars 56:61 nucleotide sugars 45:61 nucleotide sugars 45:61 High-throughput profiling of nucleotides and nucleotide sugars to evaluate their impact on antibody N-glycosylation. 27131894 0 44 from impact 81:86 arg1 N-glycosylation 100:114 antibody N-glycosylation 91:114 antibody N-glycosylation 91:114 High-throughput profiling of nucleotides and nucleotide sugars to evaluate their impact on antibody N-glycosylation. 27131894 4 45 theme glycosylation 905:917 arg1 process 894:900 the process 890:900 the process of glycosylation 890:917 Supplementation of various media additives significantly altered the intracellular nucleotides and nucleotide sugars that are inextricably linked to the process of glycosylation. 27131894 1 46 theme media 204:208 arg1 additives 210:218 media additives 204:218 media additives 204:218 Recent advances in miniaturized cell culture systems have facilitated the screening of media additives on productivity and protein quality attributes of mammalian cell cultures. 27131894 1 47 theme productivity 223:234 arg1 attributes 256:265 productivity and protein quality attributes 223:265 productivity and protein quality attributes of mammalian cell cultures 223:292 Recent advances in miniaturized cell culture systems have facilitated the screening of media additives on productivity and protein quality attributes of mammalian cell cultures. 27131894 3 48 theme nucleotides 468:478 arg1 profiling 441:449 time profiling 436:449 time profiling of intracellular nucleotides and nucleotide sugars of CHO-S cell fed-batch processes in a micro-scale bioreactor system 436:569 In this work, time profiling of intracellular nucleotides and nucleotide sugars of CHO-S cell fed-batch processes in a micro-scale bioreactor system was carried out using a recently developed high-throughput method based on matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry (TOF-MS). 27131894 4 49 attach linked 880:885 arg1 process 894:900 the process 890:900 the process of glycosylation 890:917 Supplementation of various media additives significantly altered the intracellular nucleotides and nucleotide sugars that are inextricably linked to the process of glycosylation. 27131894 4 49 attach linked 880:885 arg2 sugars 851:856 nucleotide sugars 840:856 nucleotide sugars 840:856 Supplementation of various media additives significantly altered the intracellular nucleotides and nucleotide sugars that are inextricably linked to the process of glycosylation. 27131894 4 49 attach linked 880:885 arg2 nucleotides 824:834 intracellular nucleotides 810:834 intracellular nucleotides 810:834 Supplementation of various media additives significantly altered the intracellular nucleotides and nucleotide sugars that are inextricably linked to the process of glycosylation. 27131894 3 50 theme matrix-assisted 646:660 arg1 TOF-MS 732:737 TOF-MS 732:737 TOF-MS 732:737 In this work, time profiling of intracellular nucleotides and nucleotide sugars of CHO-S cell fed-batch processes in a micro-scale bioreactor system was carried out using a recently developed high-throughput method based on matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry (TOF-MS). 27131894 3 50 theme matrix-assisted 646:660 arg1 spectrometry 718:729 matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry 646:729 matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry (TOF-MS) 646:738 In this work, time profiling of intracellular nucleotides and nucleotide sugars of CHO-S cell fed-batch processes in a micro-scale bioreactor system was carried out using a recently developed high-throughput method based on matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry (TOF-MS). 27131894 6 51 theme asparagine 1156:1165 arg1 supplementation 1167:1181 manganese and asparagine supplementation 1142:1181 manganese and asparagine supplementation 1142:1181 In contrast, manganese and asparagine supplementation altered the glycan profiles without affecting intracellular components. 27131894 3 52 theme sugars 495:500 arg1 profiling 441:449 time profiling 436:449 time profiling of intracellular nucleotides and nucleotide sugars of CHO-S cell fed-batch processes in a micro-scale bioreactor system 436:569 In this work, time profiling of intracellular nucleotides and nucleotide sugars of CHO-S cell fed-batch processes in a micro-scale bioreactor system was carried out using a recently developed high-throughput method based on matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry (TOF-MS). 27131894 7 53 theme miniaturized 1274:1285 arg1 cultures 1292:1299 miniaturized cell cultures 1274:1299 miniaturized cell cultures 1274:1299 The combination of miniaturized cell cultures and high-throughput analytical techniques serves therefore as a useful tool for future quality driven media optimization studies. 27131894 6 54 theme manganese 1142:1150 arg1 supplementation 1167:1181 manganese and asparagine supplementation 1142:1181 manganese and asparagine supplementation 1142:1181 In contrast, manganese and asparagine supplementation altered the glycan profiles without affecting intracellular components. 27131894 3 55 theme time-of-flight 698:711 arg1 TOF-MS 732:737 TOF-MS 732:737 TOF-MS 732:737 In this work, time profiling of intracellular nucleotides and nucleotide sugars of CHO-S cell fed-batch processes in a micro-scale bioreactor system was carried out using a recently developed high-throughput method based on matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry (TOF-MS). 27131894 3 55 theme time-of-flight 698:711 arg1 spectrometry 718:729 matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry 646:729 matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry (TOF-MS) 646:738 In this work, time profiling of intracellular nucleotides and nucleotide sugars of CHO-S cell fed-batch processes in a micro-scale bioreactor system was carried out using a recently developed high-throughput method based on matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry (TOF-MS). 27131894 3 56 from sugars 495:500 arg1 system 564:569 a micro-scale bioreactor system 539:569 a micro-scale bioreactor system 539:569 In this work, time profiling of intracellular nucleotides and nucleotide sugars of CHO-S cell fed-batch processes in a micro-scale bioreactor system was carried out using a recently developed high-throughput method based on matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry (TOF-MS). 27131894 2 57 theme limited 367:373 arg1 throughput 375:384 the limited throughput 363:384 the limited throughput of available analytical techniques 363:419 However, intracellular components are not routinely measured due to the limited throughput of available analytical techniques. 27131894 0 58 theme sugars 56:61 arg1 profiling 16:24 High-throughput profiling 0:24 High-throughput profiling of nucleotides and nucleotide sugars 0:61 High-throughput profiling of nucleotides and nucleotide sugars to evaluate their impact on antibody N-glycosylation. 27131894 3 59 theme cell 511:514 arg1 processes 526:534 CHO-S cell fed-batch processes 505:534 CHO-S cell fed-batch processes in a micro-scale bioreactor system 505:569 In this work, time profiling of intracellular nucleotides and nucleotide sugars of CHO-S cell fed-batch processes in a micro-scale bioreactor system was carried out using a recently developed high-throughput method based on matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry (TOF-MS). 27131894 7 60 theme media 1403:1407 arg1 studies 1422:1428 future quality driven media optimization studies 1381:1428 future quality driven media optimization studies 1381:1428 The combination of miniaturized cell cultures and high-throughput analytical techniques serves therefore as a useful tool for future quality driven media optimization studies. 27131894 4 61 dep nucleotides 824:834 arg1 the 806:808 the 806:808 the 806:808 Supplementation of various media additives significantly altered the intracellular nucleotides and nucleotide sugars that are inextricably linked to the process of glycosylation. 27131894 7 62 theme high-throughput 1305:1319 arg1 techniques 1332:1341 high-throughput analytical techniques 1305:1341 high-throughput analytical techniques 1305:1341 The combination of miniaturized cell cultures and high-throughput analytical techniques serves therefore as a useful tool for future quality driven media optimization studies. 27131894 7 63 theme cell 1287:1290 arg1 cultures 1292:1299 miniaturized cell cultures 1274:1299 miniaturized cell cultures 1274:1299 The combination of miniaturized cell cultures and high-throughput analytical techniques serves therefore as a useful tool for future quality driven media optimization studies. 27131894 1 64 theme miniaturized 136:147 arg1 systems 162:168 miniaturized cell culture systems 136:168 miniaturized cell culture systems 136:168 Recent advances in miniaturized cell culture systems have facilitated the screening of media additives on productivity and protein quality attributes of mammalian cell cultures. 27131894 5 65 theme levels 1055:1060 arg1 important 1118:1126 important 1118:1126 important 1118:1126 The results revealed that UDP-Gal synthesis appeared to be particularly limiting whereas the impact of elevated UDP-GlcNAc and GDP-Fuc levels on the final glycosylation patterns was only marginally important. 27131894 5 65 theme levels 1055:1060 arg1 impact 1013:1018 the impact 1009:1018 the impact of elevated UDP-GlcNAc and GDP-Fuc levels on the final glycosylation patterns 1009:1096 The results revealed that UDP-Gal synthesis appeared to be particularly limiting whereas the impact of elevated UDP-GlcNAc and GDP-Fuc levels on the final glycosylation patterns was only marginally important. 27131894 1 66 theme protein 240:246 arg1 attributes 256:265 productivity and protein quality attributes 223:265 productivity and protein quality attributes of mammalian cell cultures 223:292 Recent advances in miniaturized cell culture systems have facilitated the screening of media additives on productivity and protein quality attributes of mammalian cell cultures. 27131894 3 67 theme MALDI 691:695 arg1 TOF-MS 732:737 TOF-MS 732:737 TOF-MS 732:737 In this work, time profiling of intracellular nucleotides and nucleotide sugars of CHO-S cell fed-batch processes in a micro-scale bioreactor system was carried out using a recently developed high-throughput method based on matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry (TOF-MS). 27131894 3 67 theme MALDI 691:695 arg1 spectrometry 718:729 matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry 646:729 matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry (TOF-MS) 646:738 In this work, time profiling of intracellular nucleotides and nucleotide sugars of CHO-S cell fed-batch processes in a micro-scale bioreactor system was carried out using a recently developed high-throughput method based on matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry (TOF-MS). 27131894 1 68 theme cell 149:152 arg1 systems 162:168 miniaturized cell culture systems 136:168 miniaturized cell culture systems 136:168 Recent advances in miniaturized cell culture systems have facilitated the screening of media additives on productivity and protein quality attributes of mammalian cell cultures. 27131894 1 69 theme quality 248:254 arg1 attributes 256:265 productivity and protein quality attributes 223:265 productivity and protein quality attributes of mammalian cell cultures 223:292 Recent advances in miniaturized cell culture systems have facilitated the screening of media additives on productivity and protein quality attributes of mammalian cell cultures. 27131894 7 70 theme future 1381:1386 arg1 studies 1422:1428 future quality driven media optimization studies 1381:1428 future quality driven media optimization studies 1381:1428 The combination of miniaturized cell cultures and high-throughput analytical techniques serves therefore as a useful tool for future quality driven media optimization studies. 27131894 5 71 theme UDP-Gal 946:952 arg1 synthesis 954:962 UDP-Gal synthesis 946:962 UDP-Gal synthesis 946:962 The results revealed that UDP-Gal synthesis appeared to be particularly limiting whereas the impact of elevated UDP-GlcNAc and GDP-Fuc levels on the final glycosylation patterns was only marginally important. 27131894 3 72 theme laser 662:666 arg1 TOF-MS 732:737 TOF-MS 732:737 TOF-MS 732:737 In this work, time profiling of intracellular nucleotides and nucleotide sugars of CHO-S cell fed-batch processes in a micro-scale bioreactor system was carried out using a recently developed high-throughput method based on matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry (TOF-MS). 27131894 3 72 theme laser 662:666 arg1 spectrometry 718:729 matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry 646:729 matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry (TOF-MS) 646:738 In this work, time profiling of intracellular nucleotides and nucleotide sugars of CHO-S cell fed-batch processes in a micro-scale bioreactor system was carried out using a recently developed high-throughput method based on matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry (TOF-MS). 27131894 1 73 theme culture 154:160 arg1 systems 162:168 miniaturized cell culture systems 136:168 miniaturized cell culture systems 136:168 Recent advances in miniaturized cell culture systems have facilitated the screening of media additives on productivity and protein quality attributes of mammalian cell cultures. 27131894 7 74 theme quality 1388:1394 arg1 studies 1422:1428 future quality driven media optimization studies 1381:1428 future quality driven media optimization studies 1381:1428 The combination of miniaturized cell cultures and high-throughput analytical techniques serves therefore as a useful tool for future quality driven media optimization studies. 27131894 3 75 theme desorption/ionization 668:688 arg1 TOF-MS 732:737 TOF-MS 732:737 TOF-MS 732:737 In this work, time profiling of intracellular nucleotides and nucleotide sugars of CHO-S cell fed-batch processes in a micro-scale bioreactor system was carried out using a recently developed high-throughput method based on matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry (TOF-MS). 27131894 3 75 theme desorption/ionization 668:688 arg1 spectrometry 718:729 matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry 646:729 matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry (TOF-MS) 646:738 In this work, time profiling of intracellular nucleotides and nucleotide sugars of CHO-S cell fed-batch processes in a micro-scale bioreactor system was carried out using a recently developed high-throughput method based on matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry (TOF-MS). 27131894 3 76 from nucleotides 468:478 arg1 system 564:569 a micro-scale bioreactor system 539:569 a micro-scale bioreactor system 539:569 In this work, time profiling of intracellular nucleotides and nucleotide sugars of CHO-S cell fed-batch processes in a micro-scale bioreactor system was carried out using a recently developed high-throughput method based on matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry (TOF-MS). 27131894 2 77 theme available 389:397 arg1 techniques 410:419 available analytical techniques 389:419 available analytical techniques 389:419 However, intracellular components are not routinely measured due to the limited throughput of available analytical techniques. 27131894 7 78 theme driven 1396:1401 arg1 studies 1422:1428 future quality driven media optimization studies 1381:1428 future quality driven media optimization studies 1381:1428 The combination of miniaturized cell cultures and high-throughput analytical techniques serves therefore as a useful tool for future quality driven media optimization studies. 27131894 7 79 theme useful 1365:1370 arg1 combination 1259:1269 The combination 1255:1269 The combination of miniaturized cell cultures and high-throughput analytical techniques 1255:1341 The combination of miniaturized cell cultures and high-throughput analytical techniques serves therefore as a useful tool for future quality driven media optimization studies. 27131894 7 79 theme useful 1365:1370 arg1 tool 1372:1375 a useful tool 1363:1375 a useful tool for future quality driven media optimization studies 1363:1428 The combination of miniaturized cell cultures and high-throughput analytical techniques serves therefore as a useful tool for future quality driven media optimization studies. 26548339 2 0 theme bacterial 508:516 arg1 N-glycanase 526:536 a recently discovered bacterial protein N-glycanase 486:536 a recently discovered bacterial protein N-glycanase (PNGase H(+)) 486:550 The need to analyze N-glycan moieties in a highly parallel manner inspired us to develop a quick N-glycan analysis method based on a recently discovered bacterial protein N-glycanase (PNGase H(+)). 26548339 6 1 theme plant 1354:1358 arg1 sources 1360:1366 various plant sources 1346:1366 various plant sources 1346:1366 The versatility of this methodology was evaluated by analyzing glycoproteins derived from various plant sources using ultra-performance liquid chromatography (UPLC) analysis and further demonstrated through the activity analysis of four PNGase H(+) mutant variants. 26548339 6 2 dep glycoproteins 1319:1331 arg1 derived 1333:1339 derived 1333:1339 derived from various plant sources using ultra-performance liquid chromatography (UPLC) analysis 1333:1428 The versatility of this methodology was evaluated by analyzing glycoproteins derived from various plant sources using ultra-performance liquid chromatography (UPLC) analysis and further demonstrated through the activity analysis of four PNGase H(+) mutant variants. 26548339 6 2 dep glycoproteins 1319:1331 arg1 demonstrated 1442:1453 demonstrated 1442:1453 further demonstrated through the activity analysis of four PNGase H(+) mutant variants 1434:1519 The versatility of this methodology was evaluated by analyzing glycoproteins derived from various plant sources using ultra-performance liquid chromatography (UPLC) analysis and further demonstrated through the activity analysis of four PNGase H(+) mutant variants. 26548339 5 3 theme microwell-plate 1144:1158 arg1 sampling 1160:1167 microwell-plate sampling 1144:1167 microwell-plate sampling 1144:1167 All sample handling and incubation steps can be performed in less than 4 h and are compatible with microwell-plate sampling, without the need for tedious centrifugation, precipitation, or sample-transfer steps. 26548339 0 4 theme PNGase 83:88 arg1 H+ 90:91 Acid-Stable PNGase H+ 71:91 Acid-Stable PNGase H+ 71:91 Rapid Sample Preparation Methodology for Plant N-Glycan Analysis Using Acid-Stable PNGase H+. 26548339 1 5 gly glycoproteins 179:191 arg1 glycoproteins 179:191 insect glycoproteins 172:191 insect glycoproteins 172:191 The quantification of potentially allergenic carbohydrate motifs of plant and insect glycoproteins is increasingly important in biotechnological and agricultural applications as a result of the use of insect cell-based expression systems and transgenic plants. 26548339 1 6 theme insect 172:177 arg1 glycoproteins 179:191 insect glycoproteins 172:191 insect glycoproteins 172:191 The quantification of potentially allergenic carbohydrate motifs of plant and insect glycoproteins is increasingly important in biotechnological and agricultural applications as a result of the use of insect cell-based expression systems and transgenic plants. 26548339 4 7 theme deglycosylation 1023:1037 arg1 step 1039:1042 the enzymatic deglycosylation step 1009:1042 the enzymatic deglycosylation step 1009:1042 Because PNGase H(+) is highly active under acidic conditions, the consecutive fluorescence labeling step using 2-aminobenzamide (2AB) can be directly performed in the same mixture used for the enzymatic deglycosylation step. 26548339 3 8 theme derived 686:692 arg1 glycopeptides 694:706 proteolytically derived glycopeptides 670:706 proteolytically derived glycopeptides 670:706 In contrast to the traditionally used PNGase A, which is isolated from almond seeds and only releases N-glycans from proteolytically derived glycopeptides, the herein implemented PNGase H(+) allows for the release of N-glycans directly from the glycoprotein samples. 26548339 4 9 theme enzymatic 1013:1021 arg1 step 1039:1042 the enzymatic deglycosylation step 1009:1042 the enzymatic deglycosylation step 1009:1042 Because PNGase H(+) is highly active under acidic conditions, the consecutive fluorescence labeling step using 2-aminobenzamide (2AB) can be directly performed in the same mixture used for the enzymatic deglycosylation step. 26548339 1 10 theme use 288:290 arg1 result 274:279 a result 272:279 a result of the use of insect cell-based expression systems and transgenic plants 272:352 The quantification of potentially allergenic carbohydrate motifs of plant and insect glycoproteins is increasingly important in biotechnological and agricultural applications as a result of the use of insect cell-based expression systems and transgenic plants. 26548339 4 11 theme labeling 911:918 arg1 step 920:923 the consecutive fluorescence labeling step 882:923 the consecutive fluorescence labeling step using 2-aminobenzamide (2AB) 882:952 Because PNGase H(+) is highly active under acidic conditions, the consecutive fluorescence labeling step using 2-aminobenzamide (2AB) can be directly performed in the same mixture used for the enzymatic deglycosylation step. 26548339 3 12 theme implemented 720:730 arg1 H 739:739 the herein implemented PNGase H 709:739 the herein implemented PNGase H 709:739 In contrast to the traditionally used PNGase A, which is isolated from almond seeds and only releases N-glycans from proteolytically derived glycopeptides, the herein implemented PNGase H(+) allows for the release of N-glycans directly from the glycoprotein samples. 26548339 4 13 theme same 987:990 arg1 mixture 992:998 the same mixture 983:998 the same mixture used for the enzymatic deglycosylation step 983:1042 Because PNGase H(+) is highly active under acidic conditions, the consecutive fluorescence labeling step using 2-aminobenzamide (2AB) can be directly performed in the same mixture used for the enzymatic deglycosylation step. 26548339 3 14 theme glycoprotein 798:809 arg1 samples 811:817 the glycoprotein samples 794:817 the glycoprotein samples 794:817 In contrast to the traditionally used PNGase A, which is isolated from almond seeds and only releases N-glycans from proteolytically derived glycopeptides, the herein implemented PNGase H(+) allows for the release of N-glycans directly from the glycoprotein samples. 26548339 2 15 theme PNGase 539:544 arg1 H 546:546 PNGase H 539:546 PNGase H 539:546 The need to analyze N-glycan moieties in a highly parallel manner inspired us to develop a quick N-glycan analysis method based on a recently discovered bacterial protein N-glycanase (PNGase H(+)). 26548339 3 16 theme PNGase 732:737 arg1 H 739:739 the herein implemented PNGase H 709:739 the herein implemented PNGase H 709:739 In contrast to the traditionally used PNGase A, which is isolated from almond seeds and only releases N-glycans from proteolytically derived glycopeptides, the herein implemented PNGase H(+) allows for the release of N-glycans directly from the glycoprotein samples. 26548339 4 17 theme PNGase 828:833 arg1 H 835:835 PNGase H 828:835 PNGase H 828:835 Because PNGase H(+) is highly active under acidic conditions, the consecutive fluorescence labeling step using 2-aminobenzamide (2AB) can be directly performed in the same mixture used for the enzymatic deglycosylation step. 26548339 6 18 theme variants 1512:1519 arg1 analysis 1476:1483 the activity analysis 1463:1483 the activity analysis of four PNGase H(+) mutant variants 1463:1519 The versatility of this methodology was evaluated by analyzing glycoproteins derived from various plant sources using ultra-performance liquid chromatography (UPLC) analysis and further demonstrated through the activity analysis of four PNGase H(+) mutant variants. 26548339 1 19 theme glycoproteins 179:191 arg1 motifs 152:157 potentially allergenic carbohydrate motifs 116:157 potentially allergenic carbohydrate motifs of plant and insect glycoproteins 116:191 The quantification of potentially allergenic carbohydrate motifs of plant and insect glycoproteins is increasingly important in biotechnological and agricultural applications as a result of the use of insect cell-based expression systems and transgenic plants. 26548339 6 20 theme ultra-performance 1374:1390 arg1 chromatography 1399:1412 ultra-performance liquid chromatography 1374:1412 ultra-performance liquid chromatography (UPLC) analysis 1374:1428 The versatility of this methodology was evaluated by analyzing glycoproteins derived from various plant sources using ultra-performance liquid chromatography (UPLC) analysis and further demonstrated through the activity analysis of four PNGase H(+) mutant variants. 26548339 6 20 theme ultra-performance 1374:1390 arg1 UPLC 1415:1418 UPLC 1415:1418 UPLC 1415:1418 The versatility of this methodology was evaluated by analyzing glycoproteins derived from various plant sources using ultra-performance liquid chromatography (UPLC) analysis and further demonstrated through the activity analysis of four PNGase H(+) mutant variants. 26548339 5 21 theme incubation 1069:1078 arg1 steps 1080:1084 All sample handling and incubation steps 1045:1084 steps 1080:1084 All sample handling and incubation steps can be performed in less than 4 h and are compatible with microwell-plate sampling, without the need for tedious centrifugation, precipitation, or sample-transfer steps. 26548339 5 22 with compatible 1128:1137 arg1 sampling 1160:1167 microwell-plate sampling 1144:1167 microwell-plate sampling 1144:1167 All sample handling and incubation steps can be performed in less than 4 h and are compatible with microwell-plate sampling, without the need for tedious centrifugation, precipitation, or sample-transfer steps. 26548339 2 23 theme analysis 461:468 arg1 method 470:475 a quick N-glycan analysis method 444:475 a quick N-glycan analysis method based on a recently discovered bacterial protein N-glycanase (PNGase H(+)) 444:550 The need to analyze N-glycan moieties in a highly parallel manner inspired us to develop a quick N-glycan analysis method based on a recently discovered bacterial protein N-glycanase (PNGase H(+)). 26548339 4 24 theme fluorescence 898:909 arg1 step 920:923 the consecutive fluorescence labeling step 882:923 the consecutive fluorescence labeling step using 2-aminobenzamide (2AB) 882:952 Because PNGase H(+) is highly active under acidic conditions, the consecutive fluorescence labeling step using 2-aminobenzamide (2AB) can be directly performed in the same mixture used for the enzymatic deglycosylation step. 26548339 0 25 theme Sample 6:11 arg1 Preparation 13:23 Rapid Sample Preparation 0:23 Rapid Sample Preparation 0:23 Rapid Sample Preparation Methodology for Plant N-Glycan Analysis Using Acid-Stable PNGase H+. 26548339 2 26 theme discovered 497:506 arg1 N-glycanase 526:536 a recently discovered bacterial protein N-glycanase 486:536 a recently discovered bacterial protein N-glycanase (PNGase H(+)) 486:550 The need to analyze N-glycan moieties in a highly parallel manner inspired us to develop a quick N-glycan analysis method based on a recently discovered bacterial protein N-glycanase (PNGase H(+)). 26548339 2 27 theme parallel 405:412 arg1 manner 414:419 a highly parallel manner 396:419 a highly parallel manner 396:419 The need to analyze N-glycan moieties in a highly parallel manner inspired us to develop a quick N-glycan analysis method based on a recently discovered bacterial protein N-glycanase (PNGase H(+)). 26548339 0 28 theme Rapid 0:4 arg1 Preparation 13:23 Rapid Sample Preparation 0:23 Rapid Sample Preparation 0:23 Rapid Sample Preparation Methodology for Plant N-Glycan Analysis Using Acid-Stable PNGase H+. 26548339 1 29 theme insect 295:300 arg1 systems 324:330 insect cell-based expression systems 295:330 insect cell-based expression systems 295:330 The quantification of potentially allergenic carbohydrate motifs of plant and insect glycoproteins is increasingly important in biotechnological and agricultural applications as a result of the use of insect cell-based expression systems and transgenic plants. 26548339 2 30 theme N-glycan 452:459 arg1 method 470:475 a quick N-glycan analysis method 444:475 a quick N-glycan analysis method based on a recently discovered bacterial protein N-glycanase (PNGase H(+)) 444:550 The need to analyze N-glycan moieties in a highly parallel manner inspired us to develop a quick N-glycan analysis method based on a recently discovered bacterial protein N-glycanase (PNGase H(+)). 26548339 1 31 theme cell-based 302:311 arg1 systems 324:330 insect cell-based expression systems 295:330 insect cell-based expression systems 295:330 The quantification of potentially allergenic carbohydrate motifs of plant and insect glycoproteins is increasingly important in biotechnological and agricultural applications as a result of the use of insect cell-based expression systems and transgenic plants. 26548339 5 32 theme sample 1049:1054 arg1 handling 1056:1063 All sample handling and incubation steps 1045:1084 handling 1056:1063 All sample handling and incubation steps can be performed in less than 4 h and are compatible with microwell-plate sampling, without the need for tedious centrifugation, precipitation, or sample-transfer steps. 26548339 6 33 gly glycoproteins 1319:1331 arg1 glycoproteins 1319:1331 glycoproteins 1319:1331 glycoproteins derived from various plant sources using ultra-performance liquid chromatography (UPLC) analysis and further demonstrated through the activity analysis of four PNGase H(+) mutant variants 1319:1519 The versatility of this methodology was evaluated by analyzing glycoproteins derived from various plant sources using ultra-performance liquid chromatography (UPLC) analysis and further demonstrated through the activity analysis of four PNGase H(+) mutant variants. 26548339 6 34 theme various 1346:1352 arg1 sources 1360:1366 various plant sources 1346:1366 various plant sources 1346:1366 The versatility of this methodology was evaluated by analyzing glycoproteins derived from various plant sources using ultra-performance liquid chromatography (UPLC) analysis and further demonstrated through the activity analysis of four PNGase H(+) mutant variants. 26548339 3 35 link derived 686:692 arg1 glycopeptides 694:706 proteolytically derived glycopeptides 670:706 proteolytically derived glycopeptides 670:706 In contrast to the traditionally used PNGase A, which is isolated from almond seeds and only releases N-glycans from proteolytically derived glycopeptides, the herein implemented PNGase H(+) allows for the release of N-glycans directly from the glycoprotein samples. 26548339 2 36 theme quick 446:450 arg1 method 470:475 a quick N-glycan analysis method 444:475 a quick N-glycan analysis method based on a recently discovered bacterial protein N-glycanase (PNGase H(+)) 444:550 The need to analyze N-glycan moieties in a highly parallel manner inspired us to develop a quick N-glycan analysis method based on a recently discovered bacterial protein N-glycanase (PNGase H(+)). 26548339 1 37 theme expression 313:322 arg1 systems 324:330 insect cell-based expression systems 295:330 insect cell-based expression systems 295:330 The quantification of potentially allergenic carbohydrate motifs of plant and insect glycoproteins is increasingly important in biotechnological and agricultural applications as a result of the use of insect cell-based expression systems and transgenic plants. 26548339 2 38 theme N-glycan 375:382 arg1 moieties 384:391 N-glycan moieties 375:391 N-glycan moieties 375:391 The need to analyze N-glycan moieties in a highly parallel manner inspired us to develop a quick N-glycan analysis method based on a recently discovered bacterial protein N-glycanase (PNGase H(+)). 26548339 6 39 theme H 1500:1500 arg1 variants 1512:1519 four PNGase H(+) mutant variants 1488:1519 four PNGase H(+) mutant variants 1488:1519 The versatility of this methodology was evaluated by analyzing glycoproteins derived from various plant sources using ultra-performance liquid chromatography (UPLC) analysis and further demonstrated through the activity analysis of four PNGase H(+) mutant variants. 26548339 1 40 theme biotechnological 222:237 arg1 applications 256:267 biotechnological and agricultural applications 222:267 applications 256:267 The quantification of potentially allergenic carbohydrate motifs of plant and insect glycoproteins is increasingly important in biotechnological and agricultural applications as a result of the use of insect cell-based expression systems and transgenic plants. 26548339 0 41 theme Plant 41:45 arg1 Analysis 56:63 Plant N-Glycan Analysis 41:63 Plant N-Glycan Analysis Using Acid-Stable PNGase H+ 41:91 Rapid Sample Preparation Methodology for Plant N-Glycan Analysis Using Acid-Stable PNGase H+. 26548339 1 42 theme systems 324:330 arg1 use 288:290 the use 284:290 the use of insect cell-based expression systems and transgenic plants 284:352 The quantification of potentially allergenic carbohydrate motifs of plant and insect glycoproteins is increasingly important in biotechnological and agricultural applications as a result of the use of insect cell-based expression systems and transgenic plants. 26548339 3 43 from samples 811:817 arg1 release 759:765 the release 755:765 the release of N-glycans directly from the glycoprotein samples 755:817 In contrast to the traditionally used PNGase A, which is isolated from almond seeds and only releases N-glycans from proteolytically derived glycopeptides, the herein implemented PNGase H(+) allows for the release of N-glycans directly from the glycoprotein samples. 26548339 3 44 theme PNGase 591:596 arg1 A 598:598 the traditionally used PNGase A 568:598 the traditionally used PNGase A 568:598 In contrast to the traditionally used PNGase A, which is isolated from almond seeds and only releases N-glycans from proteolytically derived glycopeptides, the herein implemented PNGase H(+) allows for the release of N-glycans directly from the glycoprotein samples. 26548339 6 45 theme PNGase 1493:1498 arg1 H 1500:1500 PNGase H 1493:1500 PNGase H 1493:1500 The versatility of this methodology was evaluated by analyzing glycoproteins derived from various plant sources using ultra-performance liquid chromatography (UPLC) analysis and further demonstrated through the activity analysis of four PNGase H(+) mutant variants. 26548339 6 46 theme chromatography 1399:1412 arg1 analysis 1421:1428 ultra-performance liquid chromatography (UPLC) analysis 1374:1428 ultra-performance liquid chromatography (UPLC) analysis 1374:1428 The versatility of this methodology was evaluated by analyzing glycoproteins derived from various plant sources using ultra-performance liquid chromatography (UPLC) analysis and further demonstrated through the activity analysis of four PNGase H(+) mutant variants. 26548339 4 47 theme consecutive 886:896 arg1 step 920:923 the consecutive fluorescence labeling step 882:923 the consecutive fluorescence labeling step using 2-aminobenzamide (2AB) 882:952 Because PNGase H(+) is highly active under acidic conditions, the consecutive fluorescence labeling step using 2-aminobenzamide (2AB) can be directly performed in the same mixture used for the enzymatic deglycosylation step. 26548339 3 48 gly glycoprotein 798:809 arg1 glycoprotein 798:809 the glycoprotein samples 794:817 the glycoprotein samples 794:817 In contrast to the traditionally used PNGase A, which is isolated from almond seeds and only releases N-glycans from proteolytically derived glycopeptides, the herein implemented PNGase H(+) allows for the release of N-glycans directly from the glycoprotein samples. 26548339 1 49 theme agricultural 243:254 arg1 applications 256:267 biotechnological and agricultural applications 222:267 applications 256:267 The quantification of potentially allergenic carbohydrate motifs of plant and insect glycoproteins is increasingly important in biotechnological and agricultural applications as a result of the use of insect cell-based expression systems and transgenic plants. 26548339 6 50 theme liquid 1392:1397 arg1 chromatography 1399:1412 ultra-performance liquid chromatography 1374:1412 ultra-performance liquid chromatography (UPLC) analysis 1374:1428 The versatility of this methodology was evaluated by analyzing glycoproteins derived from various plant sources using ultra-performance liquid chromatography (UPLC) analysis and further demonstrated through the activity analysis of four PNGase H(+) mutant variants. 26548339 6 50 theme liquid 1392:1397 arg1 UPLC 1415:1418 UPLC 1415:1418 UPLC 1415:1418 The versatility of this methodology was evaluated by analyzing glycoproteins derived from various plant sources using ultra-performance liquid chromatography (UPLC) analysis and further demonstrated through the activity analysis of four PNGase H(+) mutant variants. 26548339 1 51 theme transgenic 336:345 arg1 plants 347:352 transgenic plants 336:352 transgenic plants 336:352 The quantification of potentially allergenic carbohydrate motifs of plant and insect glycoproteins is increasingly important in biotechnological and agricultural applications as a result of the use of insect cell-based expression systems and transgenic plants. 26548339 3 52 theme almond 624:629 arg1 seeds 631:635 almond seeds 624:635 almond seeds 624:635 In contrast to the traditionally used PNGase A, which is isolated from almond seeds and only releases N-glycans from proteolytically derived glycopeptides, the herein implemented PNGase H(+) allows for the release of N-glycans directly from the glycoprotein samples. 26548339 2 53 dep N-glycanase 526:536 arg1 H 546:546 PNGase H 539:546 PNGase H 539:546 The need to analyze N-glycan moieties in a highly parallel manner inspired us to develop a quick N-glycan analysis method based on a recently discovered bacterial protein N-glycanase (PNGase H(+)). 26548339 0 54 theme N-Glycan 47:54 arg1 Analysis 56:63 Plant N-Glycan Analysis 41:63 Plant N-Glycan Analysis Using Acid-Stable PNGase H+ 41:91 Rapid Sample Preparation Methodology for Plant N-Glycan Analysis Using Acid-Stable PNGase H+. 26548339 1 55 theme plants 347:352 arg1 use 288:290 the use 284:290 the use of insect cell-based expression systems and transgenic plants 284:352 The quantification of potentially allergenic carbohydrate motifs of plant and insect glycoproteins is increasingly important in biotechnological and agricultural applications as a result of the use of insect cell-based expression systems and transgenic plants. 26548339 3 56 theme used 586:589 arg1 A 598:598 the traditionally used PNGase A 568:598 the traditionally used PNGase A 568:598 In contrast to the traditionally used PNGase A, which is isolated from almond seeds and only releases N-glycans from proteolytically derived glycopeptides, the herein implemented PNGase H(+) allows for the release of N-glycans directly from the glycoprotein samples. 26548339 1 57 theme allergenic 128:137 arg1 motifs 152:157 potentially allergenic carbohydrate motifs 116:157 potentially allergenic carbohydrate motifs of plant and insect glycoproteins 116:191 The quantification of potentially allergenic carbohydrate motifs of plant and insect glycoproteins is increasingly important in biotechnological and agricultural applications as a result of the use of insect cell-based expression systems and transgenic plants. 26548339 3 58 attach isolated 610:617 arg1 seeds 631:635 almond seeds 624:635 almond seeds 624:635 In contrast to the traditionally used PNGase A, which is isolated from almond seeds and only releases N-glycans from proteolytically derived glycopeptides, the herein implemented PNGase H(+) allows for the release of N-glycans directly from the glycoprotein samples. 26548339 3 58 attach isolated 610:617 arg2 A 598:598 the traditionally used PNGase A 568:598 the traditionally used PNGase A 568:598 In contrast to the traditionally used PNGase A, which is isolated from almond seeds and only releases N-glycans from proteolytically derived glycopeptides, the herein implemented PNGase H(+) allows for the release of N-glycans directly from the glycoprotein samples. 26548339 1 59 from applications 256:267 arg1 important 209:217 important 209:217 important 209:217 The quantification of potentially allergenic carbohydrate motifs of plant and insect glycoproteins is increasingly important in biotechnological and agricultural applications as a result of the use of insect cell-based expression systems and transgenic plants. 26548339 1 59 from applications 256:267 arg1 quantification 98:111 The quantification 94:111 The quantification of potentially allergenic carbohydrate motifs of plant and insect glycoproteins 94:191 The quantification of potentially allergenic carbohydrate motifs of plant and insect glycoproteins is increasingly important in biotechnological and agricultural applications as a result of the use of insect cell-based expression systems and transgenic plants. 26548339 1 60 theme carbohydrate 139:150 arg1 motifs 152:157 potentially allergenic carbohydrate motifs 116:157 potentially allergenic carbohydrate motifs of plant and insect glycoproteins 116:191 The quantification of potentially allergenic carbohydrate motifs of plant and insect glycoproteins is increasingly important in biotechnological and agricultural applications as a result of the use of insect cell-based expression systems and transgenic plants. 26548339 5 61 theme sample-transfer 1233:1247 arg1 steps 1249:1253 sample-transfer steps 1233:1253 sample-transfer steps 1233:1253 All sample handling and incubation steps can be performed in less than 4 h and are compatible with microwell-plate sampling, without the need for tedious centrifugation, precipitation, or sample-transfer steps. 26548339 6 62 theme methodology 1280:1290 arg1 versatility 1260:1270 The versatility 1256:1270 The versatility of this methodology 1256:1290 The versatility of this methodology was evaluated by analyzing glycoproteins derived from various plant sources using ultra-performance liquid chromatography (UPLC) analysis and further demonstrated through the activity analysis of four PNGase H(+) mutant variants. 26548339 4 63 theme acidic 863:868 arg1 conditions 870:879 acidic conditions 863:879 acidic conditions 863:879 Because PNGase H(+) is highly active under acidic conditions, the consecutive fluorescence labeling step using 2-aminobenzamide (2AB) can be directly performed in the same mixture used for the enzymatic deglycosylation step. 26548339 1 64 theme motifs 152:157 arg1 important 209:217 important 209:217 important 209:217 The quantification of potentially allergenic carbohydrate motifs of plant and insect glycoproteins is increasingly important in biotechnological and agricultural applications as a result of the use of insect cell-based expression systems and transgenic plants. 26548339 1 64 theme motifs 152:157 arg1 quantification 98:111 The quantification 94:111 The quantification of potentially allergenic carbohydrate motifs of plant and insect glycoproteins 94:191 The quantification of potentially allergenic carbohydrate motifs of plant and insect glycoproteins is increasingly important in biotechnological and agricultural applications as a result of the use of insect cell-based expression systems and transgenic plants. 26548339 6 65 theme mutant 1505:1510 arg1 variants 1512:1519 four PNGase H(+) mutant variants 1488:1519 four PNGase H(+) mutant variants 1488:1519 The versatility of this methodology was evaluated by analyzing glycoproteins derived from various plant sources using ultra-performance liquid chromatography (UPLC) analysis and further demonstrated through the activity analysis of four PNGase H(+) mutant variants. 26548339 0 66 theme Acid-Stable 71:81 arg1 H+ 90:91 Acid-Stable PNGase H+ 71:91 Acid-Stable PNGase H+ 71:91 Rapid Sample Preparation Methodology for Plant N-Glycan Analysis Using Acid-Stable PNGase H+. 26548339 1 67 from important 209:217 arg1 applications 256:267 biotechnological and agricultural applications 222:267 applications 256:267 The quantification of potentially allergenic carbohydrate motifs of plant and insect glycoproteins is increasingly important in biotechnological and agricultural applications as a result of the use of insect cell-based expression systems and transgenic plants. 26548339 5 68 theme tedious 1191:1197 arg1 centrifugation 1199:1212 tedious centrifugation 1191:1212 tedious centrifugation 1191:1212 All sample handling and incubation steps can be performed in less than 4 h and are compatible with microwell-plate sampling, without the need for tedious centrifugation, precipitation, or sample-transfer steps. 26548339 6 69 theme activity 1467:1474 arg1 analysis 1476:1483 the activity analysis 1463:1483 the activity analysis of four PNGase H(+) mutant variants 1463:1519 The versatility of this methodology was evaluated by analyzing glycoproteins derived from various plant sources using ultra-performance liquid chromatography (UPLC) analysis and further demonstrated through the activity analysis of four PNGase H(+) mutant variants. 26548339 2 70 theme protein 518:524 arg1 N-glycanase 526:536 a recently discovered bacterial protein N-glycanase 486:536 a recently discovered bacterial protein N-glycanase (PNGase H(+)) 486:550 The need to analyze N-glycan moieties in a highly parallel manner inspired us to develop a quick N-glycan analysis method based on a recently discovered bacterial protein N-glycanase (PNGase H(+)). 26548339 3 71 theme N-glycans 770:778 arg1 release 759:765 the release 755:765 the release of N-glycans directly from the glycoprotein samples 755:817 In contrast to the traditionally used PNGase A, which is isolated from almond seeds and only releases N-glycans from proteolytically derived glycopeptides, the herein implemented PNGase H(+) allows for the release of N-glycans directly from the glycoprotein samples. 26548339 1 72 theme plant 162:166 arg1 motifs 152:157 potentially allergenic carbohydrate motifs 116:157 potentially allergenic carbohydrate motifs of plant and insect glycoproteins 116:191 The quantification of potentially allergenic carbohydrate motifs of plant and insect glycoproteins is increasingly important in biotechnological and agricultural applications as a result of the use of insect cell-based expression systems and transgenic plants. 26548339 3 73 gly glycopeptides 694:706 arg2 glycopeptides 694:706 proteolytically derived glycopeptides 670:706 proteolytically derived glycopeptides 670:706 In contrast to the traditionally used PNGase A, which is isolated from almond seeds and only releases N-glycans from proteolytically derived glycopeptides, the herein implemented PNGase H(+) allows for the release of N-glycans directly from the glycoprotein samples. 27037250 2 0 from role 480:483 arg1 regulation 528:537 endoplasmic reticulum (ER)-situated DLO regulation 488:537 endoplasmic reticulum (ER)-situated DLO regulation 488:537 An OSP-generating activity has been reported in vitro, and here we asked if its biochemical characteristics are compatible with a role in endoplasmic reticulum (ER)-situated DLO regulation. 27037250 5 1 theme chains 825:830 arg1 length 803:808 the length 799:808 the length of their alkyl chains 799:830 Polyprenyl diphosphates inhibit [(3)H]OSP release from [(3)H]DLO, the length of their alkyl chains correlating positively with inhibition potency. 27037250 7 2 theme microsomal 1149:1158 arg1 markers 1160:1166 microsomal markers 1149:1166 microsomal markers 1149:1166 During subcellular fractionation of liver homogenates, DLODP codistributes with microsomal markers, and density gradient centrifugation revealed that the distribution of DLODP is closer to that of Golgi apparatus-situated UDP-galactose glycoprotein galactosyltransferase than those of dolichyl-P-dependent glycosyltransferases required for DLO biosynthesis in the ER. 27037250 2 3 with compatible 462:471 arg1 role 480:483 a role 478:483 a role in endoplasmic reticulum (ER)-situated DLO regulation 478:537 An OSP-generating activity has been reported in vitro, and here we asked if its biochemical characteristics are compatible with a role in endoplasmic reticulum (ER)-situated DLO regulation. 27037250 7 4 theme density 1173:1179 arg1 centrifugation 1190:1203 density gradient centrifugation 1173:1203 density gradient centrifugation 1173:1203 During subcellular fractionation of liver homogenates, DLODP codistributes with microsomal markers, and density gradient centrifugation revealed that the distribution of DLODP is closer to that of Golgi apparatus-situated UDP-galactose glycoprotein galactosyltransferase than those of dolichyl-P-dependent glycosyltransferases required for DLO biosynthesis in the ER. 27037250 7 5 theme subcellular 1076:1086 arg1 fractionation 1088:1100 subcellular fractionation 1076:1100 subcellular fractionation of liver homogenates 1076:1121 During subcellular fractionation of liver homogenates, DLODP codistributes with microsomal markers, and density gradient centrifugation revealed that the distribution of DLODP is closer to that of Golgi apparatus-situated UDP-galactose glycoprotein galactosyltransferase than those of dolichyl-P-dependent glycosyltransferases required for DLO biosynthesis in the ER. 27037250 9 6 theme DLO 1667:1669 arg1 biosynthesis 1671:1682 DLO biosynthesis 1667:1682 DLO biosynthesis 1667:1682 Separate subcellular locations for DLODP action and DLO biosynthesis may be required to prevent uncontrolled DLO destruction. 27037250 3 7 theme diphosphatase 578:590 arg1 activity 600:607 a Co(2+)-dependent DLO diphosphatase (DLODP) activity 555:607 a Co(2+)-dependent DLO diphosphatase (DLODP) activity that splits DLO into dolichyl phosphate and OSP 555:655 We demonstrate a Co(2+)-dependent DLO diphosphatase (DLODP) activity that splits DLO into dolichyl phosphate and OSP. 27037250 6 8 from DLO 997:999 arg1 release 978:984 OSP release 974:984 [(3)H]OSP release from [(3)H]DLO 968:999 The diphosphodiester GlcNAc2-PP-solanesol is hydrolyzed to yield GlcNAc2-P and inhibits [(3)H]OSP release from [(3)H]DLO more effectively than the diphosphomonoester solanesyl diphosphate. 27037250 6 8 from DLO 997:999 arg1 H 972:972 (3)H 969:972 (3)H 969:972 The diphosphodiester GlcNAc2-PP-solanesol is hydrolyzed to yield GlcNAc2-P and inhibits [(3)H]OSP release from [(3)H]DLO more effectively than the diphosphomonoester solanesyl diphosphate. 27037250 1 9 theme uncharacterized 325:339 arg1 process 341:347 an uncharacterized process 322:347 an uncharacterized process 322:347 Oligosaccharyl phosphates (OSPs) are hydrolyzed from oligosaccharide-diphosphodolichol (DLO) during protein N-glycosylation by an uncharacterized process. 27037250 5 10 theme Polyprenyl 733:742 arg1 diphosphates 744:755 Polyprenyl diphosphates 733:755 Polyprenyl diphosphates 733:755 Polyprenyl diphosphates inhibit [(3)H]OSP release from [(3)H]DLO, the length of their alkyl chains correlating positively with inhibition potency. 27037250 9 11 theme DLO 1724:1726 arg1 destruction 1728:1738 uncontrolled DLO destruction 1711:1738 uncontrolled DLO destruction 1711:1738 Separate subcellular locations for DLODP action and DLO biosynthesis may be required to prevent uncontrolled DLO destruction. 27037250 2 12 theme OSP-generating 353:366 arg1 activity 368:375 An OSP-generating activity 350:375 An OSP-generating activity 350:375 An OSP-generating activity has been reported in vitro, and here we asked if its biochemical characteristics are compatible with a role in endoplasmic reticulum (ER)-situated DLO regulation. 27037250 7 13 theme homogenates 1111:1121 arg1 fractionation 1088:1100 subcellular fractionation 1076:1100 subcellular fractionation of liver homogenates 1076:1121 During subcellular fractionation of liver homogenates, DLODP codistributes with microsomal markers, and density gradient centrifugation revealed that the distribution of DLODP is closer to that of Golgi apparatus-situated UDP-galactose glycoprotein galactosyltransferase than those of dolichyl-P-dependent glycosyltransferases required for DLO biosynthesis in the ER. 27037250 7 14 theme dolichyl-P-dependent 1354:1373 arg1 glycosyltransferases 1375:1394 dolichyl-P-dependent glycosyltransferases 1354:1394 dolichyl-P-dependent glycosyltransferases required for DLO biosynthesis in the ER 1354:1434 During subcellular fractionation of liver homogenates, DLODP codistributes with microsomal markers, and density gradient centrifugation revealed that the distribution of DLODP is closer to that of Golgi apparatus-situated UDP-galactose glycoprotein galactosyltransferase than those of dolichyl-P-dependent glycosyltransferases required for DLO biosynthesis in the ER. 27037250 3 15 theme -dependent 563:572 arg1 activity 600:607 a Co(2+)-dependent DLO diphosphatase (DLODP) activity 555:607 a Co(2+)-dependent DLO diphosphatase (DLODP) activity that splits DLO into dolichyl phosphate and OSP 555:655 We demonstrate a Co(2+)-dependent DLO diphosphatase (DLODP) activity that splits DLO into dolichyl phosphate and OSP. 27037250 0 16 theme dolichyl-phosphate-dependent 135:162 arg1 enzymes 164:170 dolichyl-phosphate-dependent enzymes 135:170 dolichyl-phosphate-dependent enzymes of the dolichol cycle 135:192 Demonstration of an oligosaccharide-diphosphodolichol diphosphatase activity whose subcellular localization is different than those of dolichyl-phosphate-dependent enzymes of the dolichol cycle. 27037250 6 17 dep H 972:972 arg1 3 970:970 3 970:970 3 970:970 The diphosphodiester GlcNAc2-PP-solanesol is hydrolyzed to yield GlcNAc2-P and inhibits [(3)H]OSP release from [(3)H]DLO more effectively than the diphosphomonoester solanesyl diphosphate. 27037250 8 18 from phosphatases 1586:1597 arg1 distinct 1560:1567 distinct 1560:1567 distinct 1560:1567 Therefore, a DLODP activity showing selectivity toward lipophilic diphosphodiesters such as DLO, and possessing properties distinct from other lipid phosphatases, is identified. 27037250 3 19 theme DLO 574:576 arg1 diphosphatase 578:590 DLO diphosphatase 574:590 a Co(2+)-dependent DLO diphosphatase (DLODP) activity that splits DLO into dolichyl phosphate and OSP 555:655 We demonstrate a Co(2+)-dependent DLO diphosphatase (DLODP) activity that splits DLO into dolichyl phosphate and OSP. 27037250 3 19 theme DLO 574:576 arg1 DLODP 593:597 DLODP 593:597 DLODP 593:597 We demonstrate a Co(2+)-dependent DLO diphosphatase (DLODP) activity that splits DLO into dolichyl phosphate and OSP. 27037250 7 20 theme Golgi 1266:1270 arg1 galactosyltransferase 1318:1338 Golgi apparatus-situated UDP-galactose glycoprotein galactosyltransferase 1266:1338 Golgi apparatus-situated UDP-galactose glycoprotein galactosyltransferase 1266:1338 During subcellular fractionation of liver homogenates, DLODP codistributes with microsomal markers, and density gradient centrifugation revealed that the distribution of DLODP is closer to that of Golgi apparatus-situated UDP-galactose glycoprotein galactosyltransferase than those of dolichyl-P-dependent glycosyltransferases required for DLO biosynthesis in the ER. 27037250 5 21 dep H 769:769 arg1 3 767:767 3 767:767 3 767:767 Polyprenyl diphosphates inhibit [(3)H]OSP release from [(3)H]DLO, the length of their alkyl chains correlating positively with inhibition potency. 27037250 7 22 gly glycoprotein 1305:1316 arg1 glycoprotein 1305:1316 Golgi apparatus-situated UDP-galactose glycoprotein galactosyltransferase 1266:1338 Golgi apparatus-situated UDP-galactose glycoprotein galactosyltransferase 1266:1338 During subcellular fractionation of liver homogenates, DLODP codistributes with microsomal markers, and density gradient centrifugation revealed that the distribution of DLODP is closer to that of Golgi apparatus-situated UDP-galactose glycoprotein galactosyltransferase than those of dolichyl-P-dependent glycosyltransferases required for DLO biosynthesis in the ER. 27037250 7 23 theme DLO 1409:1411 arg1 biosynthesis 1413:1424 DLO biosynthesis 1409:1424 DLO biosynthesis in the ER 1409:1434 During subcellular fractionation of liver homogenates, DLODP codistributes with microsomal markers, and density gradient centrifugation revealed that the distribution of DLODP is closer to that of Golgi apparatus-situated UDP-galactose glycoprotein galactosyltransferase than those of dolichyl-P-dependent glycosyltransferases required for DLO biosynthesis in the ER. 27037250 2 24 theme biochemical 430:440 arg1 characteristics 442:456 its biochemical characteristics 426:456 its biochemical characteristics 426:456 An OSP-generating activity has been reported in vitro, and here we asked if its biochemical characteristics are compatible with a role in endoplasmic reticulum (ER)-situated DLO regulation. 27037250 0 25 theme oligosaccharide-diphosphodolichol 20:52 arg1 Demonstration 0:12 Demonstration 0:12 Demonstration of an oligosaccharide-diphosphodolichol 0:52 Demonstration of an oligosaccharide-diphosphodolichol diphosphatase activity whose subcellular localization is different than those of dolichyl-phosphate-dependent enzymes of the dolichol cycle. 27037250 9 26 theme DLODP 1650:1654 arg1 action 1656:1661 DLODP action 1650:1661 DLODP action 1650:1661 Separate subcellular locations for DLODP action and DLO biosynthesis may be required to prevent uncontrolled DLO destruction. 27037250 5 27 theme OSP 771:773 arg1 release 775:781 OSP release 771:781 OSP release from [(3)H]DLO 771:796 Polyprenyl diphosphates inhibit [(3)H]OSP release from [(3)H]DLO, the length of their alkyl chains correlating positively with inhibition potency. 27037250 9 28 theme subcellular 1624:1634 arg1 locations 1636:1644 Separate subcellular locations 1615:1644 Separate subcellular locations for DLODP action and DLO biosynthesis 1615:1682 Separate subcellular locations for DLODP action and DLO biosynthesis may be required to prevent uncontrolled DLO destruction. 27037250 2 29 theme endoplasmic 488:498 arg1 ER 511:512 ER 511:512 ER 511:512 An OSP-generating activity has been reported in vitro, and here we asked if its biochemical characteristics are compatible with a role in endoplasmic reticulum (ER)-situated DLO regulation. 27037250 2 29 theme endoplasmic 488:498 arg1 reticulum 500:508 endoplasmic reticulum 488:508 endoplasmic reticulum (ER)-situated DLO regulation 488:537 An OSP-generating activity has been reported in vitro, and here we asked if its biochemical characteristics are compatible with a role in endoplasmic reticulum (ER)-situated DLO regulation. 27037250 8 30 dep activity 1456:1463 arg1 possessing 1538:1547 possessing 1538:1547 possessing properties distinct from other lipid phosphatases 1538:1597 Therefore, a DLODP activity showing selectivity toward lipophilic diphosphodiesters such as DLO, and possessing properties distinct from other lipid phosphatases, is identified. 27037250 8 30 dep activity 1456:1463 arg1 showing 1465:1471 showing 1465:1471 showing selectivity toward lipophilic diphosphodiesters such as DLO 1465:1531 Therefore, a DLODP activity showing selectivity toward lipophilic diphosphodiesters such as DLO, and possessing properties distinct from other lipid phosphatases, is identified. 27037250 9 31 theme uncontrolled 1711:1722 arg1 destruction 1728:1738 uncontrolled DLO destruction 1711:1738 uncontrolled DLO destruction 1711:1738 Separate subcellular locations for DLODP action and DLO biosynthesis may be required to prevent uncontrolled DLO destruction. 27037250 6 32 theme solanesyl 1046:1054 arg1 diphosphate 1056:1066 the diphosphomonoester solanesyl diphosphate 1023:1066 the diphosphomonoester solanesyl diphosphate 1023:1066 The diphosphodiester GlcNAc2-PP-solanesol is hydrolyzed to yield GlcNAc2-P and inhibits [(3)H]OSP release from [(3)H]DLO more effectively than the diphosphomonoester solanesyl diphosphate. 27037250 8 33 theme distinct 1560:1567 arg1 properties 1549:1558 properties 1549:1558 properties distinct from other lipid phosphatases 1549:1597 Therefore, a DLODP activity showing selectivity toward lipophilic diphosphodiesters such as DLO, and possessing properties distinct from other lipid phosphatases, is identified. 27037250 0 34 theme cycle 188:192 arg1 enzymes 164:170 dolichyl-phosphate-dependent enzymes 135:170 dolichyl-phosphate-dependent enzymes of the dolichol cycle 135:192 Demonstration of an oligosaccharide-diphosphodolichol diphosphatase activity whose subcellular localization is different than those of dolichyl-phosphate-dependent enzymes of the dolichol cycle. 27037250 6 35 theme OSP 974:976 arg1 release 978:984 OSP release 974:984 [(3)H]OSP release from [(3)H]DLO 968:999 The diphosphodiester GlcNAc2-PP-solanesol is hydrolyzed to yield GlcNAc2-P and inhibits [(3)H]OSP release from [(3)H]DLO more effectively than the diphosphomonoester solanesyl diphosphate. 27037250 6 35 theme OSP 974:976 arg1 H 972:972 (3)H 969:972 (3)H 969:972 The diphosphodiester GlcNAc2-PP-solanesol is hydrolyzed to yield GlcNAc2-P and inhibits [(3)H]OSP release from [(3)H]DLO more effectively than the diphosphomonoester solanesyl diphosphate. 27037250 4 36 theme 5.5 684:686 arg1 optimum 673:679 a pH optimum 668:679 a pH optimum of 5.5 668:686 DLODP has a pH optimum of 5.5 and is inhibited by vanadate but not by NaF. 27037250 4 37 theme pH 670:671 arg1 optimum 673:679 a pH optimum 668:679 a pH optimum of 5.5 668:686 DLODP has a pH optimum of 5.5 and is inhibited by vanadate but not by NaF. 27037250 2 38 theme DLO 524:526 arg1 regulation 528:537 endoplasmic reticulum (ER)-situated DLO regulation 488:537 endoplasmic reticulum (ER)-situated DLO regulation 488:537 An OSP-generating activity has been reported in vitro, and here we asked if its biochemical characteristics are compatible with a role in endoplasmic reticulum (ER)-situated DLO regulation. 27037250 8 39 theme lipid 1580:1584 arg1 phosphatases 1586:1597 other lipid phosphatases 1574:1597 other lipid phosphatases 1574:1597 Therefore, a DLODP activity showing selectivity toward lipophilic diphosphodiesters such as DLO, and possessing properties distinct from other lipid phosphatases, is identified. 27037250 0 40 theme dolichol 179:186 arg1 cycle 188:192 the dolichol cycle 175:192 the dolichol cycle 175:192 Demonstration of an oligosaccharide-diphosphodolichol diphosphatase activity whose subcellular localization is different than those of dolichyl-phosphate-dependent enzymes of the dolichol cycle. 27037250 3 41 theme dolichyl 630:637 arg1 phosphate 639:647 dolichyl phosphate 630:647 dolichyl phosphate 630:647 We demonstrate a Co(2+)-dependent DLO diphosphatase (DLODP) activity that splits DLO into dolichyl phosphate and OSP. 27037250 7 42 theme DLODP 1239:1243 arg1 closer 1248:1253 closer 1248:1253 closer 1248:1253 During subcellular fractionation of liver homogenates, DLODP codistributes with microsomal markers, and density gradient centrifugation revealed that the distribution of DLODP is closer to that of Golgi apparatus-situated UDP-galactose glycoprotein galactosyltransferase than those of dolichyl-P-dependent glycosyltransferases required for DLO biosynthesis in the ER. 27037250 7 42 theme DLODP 1239:1243 arg1 distribution 1223:1234 the distribution 1219:1234 the distribution of DLODP 1219:1243 During subcellular fractionation of liver homogenates, DLODP codistributes with microsomal markers, and density gradient centrifugation revealed that the distribution of DLODP is closer to that of Golgi apparatus-situated UDP-galactose glycoprotein galactosyltransferase than those of dolichyl-P-dependent glycosyltransferases required for DLO biosynthesis in the ER. 27037250 2 43 theme -situated 514:522 arg1 regulation 528:537 endoplasmic reticulum (ER)-situated DLO regulation 488:537 endoplasmic reticulum (ER)-situated DLO regulation 488:537 An OSP-generating activity has been reported in vitro, and here we asked if its biochemical characteristics are compatible with a role in endoplasmic reticulum (ER)-situated DLO regulation. 27037250 6 44 theme diphosphodiester 884:899 arg1 GlcNAc2-PP-solanesol 901:920 The diphosphodiester GlcNAc2-PP-solanesol 880:920 The diphosphodiester GlcNAc2-PP-solanesol 880:920 The diphosphodiester GlcNAc2-PP-solanesol is hydrolyzed to yield GlcNAc2-P and inhibits [(3)H]OSP release from [(3)H]DLO more effectively than the diphosphomonoester solanesyl diphosphate. 27037250 4 45 contain has 664:666 arg1 DLODP 658:662 DLODP 658:662 DLODP 658:662 DLODP has a pH optimum of 5.5 and is inhibited by vanadate but not by NaF. 27037250 4 45 contain has 664:666 arg2 optimum 673:679 a pH optimum 668:679 a pH optimum of 5.5 668:686 DLODP has a pH optimum of 5.5 and is inhibited by vanadate but not by NaF. 27037250 5 46 from DLO 794:796 arg1 release 775:781 OSP release 771:781 OSP release from [(3)H]DLO 771:796 Polyprenyl diphosphates inhibit [(3)H]OSP release from [(3)H]DLO, the length of their alkyl chains correlating positively with inhibition potency. 27037250 6 47 theme diphosphomonoester 1027:1044 arg1 diphosphate 1056:1066 the diphosphomonoester solanesyl diphosphate 1023:1066 the diphosphomonoester solanesyl diphosphate 1023:1066 The diphosphodiester GlcNAc2-PP-solanesol is hydrolyzed to yield GlcNAc2-P and inhibits [(3)H]OSP release from [(3)H]DLO more effectively than the diphosphomonoester solanesyl diphosphate. 27037250 2 48 theme reticulum 500:508 arg1 regulation 528:537 endoplasmic reticulum (ER)-situated DLO regulation 488:537 endoplasmic reticulum (ER)-situated DLO regulation 488:537 An OSP-generating activity has been reported in vitro, and here we asked if its biochemical characteristics are compatible with a role in endoplasmic reticulum (ER)-situated DLO regulation. 27037250 5 49 dep inhibit 757:763 arg1 H 769:769 (3)H 766:769 (3)H 766:769 Polyprenyl diphosphates inhibit [(3)H]OSP release from [(3)H]DLO, the length of their alkyl chains correlating positively with inhibition potency. 27037250 9 50 theme Separate 1615:1622 arg1 locations 1636:1644 Separate subcellular locations 1615:1644 Separate subcellular locations for DLODP action and DLO biosynthesis 1615:1682 Separate subcellular locations for DLODP action and DLO biosynthesis may be required to prevent uncontrolled DLO destruction. 27037250 7 51 theme UDP-galactose 1291:1303 arg1 galactosyltransferase 1318:1338 Golgi apparatus-situated UDP-galactose glycoprotein galactosyltransferase 1266:1338 Golgi apparatus-situated UDP-galactose glycoprotein galactosyltransferase 1266:1338 During subcellular fractionation of liver homogenates, DLODP codistributes with microsomal markers, and density gradient centrifugation revealed that the distribution of DLODP is closer to that of Golgi apparatus-situated UDP-galactose glycoprotein galactosyltransferase than those of dolichyl-P-dependent glycosyltransferases required for DLO biosynthesis in the ER. 27037250 8 52 theme DLODP 1450:1454 arg1 activity 1456:1463 a DLODP activity 1448:1463 a DLODP activity 1448:1463 Therefore, a DLODP activity showing selectivity toward lipophilic diphosphodiesters such as DLO, and possessing properties distinct from other lipid phosphatases, is identified. 27037250 7 53 theme glycoprotein 1305:1316 arg1 galactosyltransferase 1318:1338 Golgi apparatus-situated UDP-galactose glycoprotein galactosyltransferase 1266:1338 Golgi apparatus-situated UDP-galactose glycoprotein galactosyltransferase 1266:1338 During subcellular fractionation of liver homogenates, DLODP codistributes with microsomal markers, and density gradient centrifugation revealed that the distribution of DLODP is closer to that of Golgi apparatus-situated UDP-galactose glycoprotein galactosyltransferase than those of dolichyl-P-dependent glycosyltransferases required for DLO biosynthesis in the ER. 27037250 6 54 dep H 995:995 arg1 3 993:993 3 993:993 3 993:993 The diphosphodiester GlcNAc2-PP-solanesol is hydrolyzed to yield GlcNAc2-P and inhibits [(3)H]OSP release from [(3)H]DLO more effectively than the diphosphomonoester solanesyl diphosphate. 27037250 5 55 theme inhibition 860:869 arg1 potency 871:877 inhibition potency 860:877 inhibition potency 860:877 Polyprenyl diphosphates inhibit [(3)H]OSP release from [(3)H]DLO, the length of their alkyl chains correlating positively with inhibition potency. 27037250 5 56 theme alkyl 819:823 arg1 chains 825:830 their alkyl chains 813:830 their alkyl chains 813:830 Polyprenyl diphosphates inhibit [(3)H]OSP release from [(3)H]DLO, the length of their alkyl chains correlating positively with inhibition potency. 27037250 7 57 theme apparatus-situated 1272:1289 arg1 galactosyltransferase 1318:1338 Golgi apparatus-situated UDP-galactose glycoprotein galactosyltransferase 1266:1338 Golgi apparatus-situated UDP-galactose glycoprotein galactosyltransferase 1266:1338 During subcellular fractionation of liver homogenates, DLODP codistributes with microsomal markers, and density gradient centrifugation revealed that the distribution of DLODP is closer to that of Golgi apparatus-situated UDP-galactose glycoprotein galactosyltransferase than those of dolichyl-P-dependent glycosyltransferases required for DLO biosynthesis in the ER. 27037250 7 58 from biosynthesis 1413:1424 arg1 ER 1433:1434 the ER 1429:1434 the ER 1429:1434 During subcellular fractionation of liver homogenates, DLODP codistributes with microsomal markers, and density gradient centrifugation revealed that the distribution of DLODP is closer to that of Golgi apparatus-situated UDP-galactose glycoprotein galactosyltransferase than those of dolichyl-P-dependent glycosyltransferases required for DLO biosynthesis in the ER. 27037250 7 59 theme gradient 1181:1188 arg1 centrifugation 1190:1203 density gradient centrifugation 1173:1203 density gradient centrifugation 1173:1203 During subcellular fractionation of liver homogenates, DLODP codistributes with microsomal markers, and density gradient centrifugation revealed that the distribution of DLODP is closer to that of Golgi apparatus-situated UDP-galactose glycoprotein galactosyltransferase than those of dolichyl-P-dependent glycosyltransferases required for DLO biosynthesis in the ER. 27037250 1 60 theme protein 295:301 arg1 N-glycosylation 303:317 protein N-glycosylation 295:317 protein N-glycosylation 295:317 Oligosaccharyl phosphates (OSPs) are hydrolyzed from oligosaccharide-diphosphodolichol (DLO) during protein N-glycosylation by an uncharacterized process. 27037250 0 61 theme subcellular 83:93 arg1 localization 95:106 localization 95:106 localization 95:106 Demonstration of an oligosaccharide-diphosphodolichol diphosphatase activity whose subcellular localization is different than those of dolichyl-phosphate-dependent enzymes of the dolichol cycle. 27037250 8 62 theme lipophilic 1492:1501 arg1 diphosphodiesters 1503:1519 lipophilic diphosphodiesters 1492:1519 lipophilic diphosphodiesters such as DLO 1492:1531 Therefore, a DLODP activity showing selectivity toward lipophilic diphosphodiesters such as DLO, and possessing properties distinct from other lipid phosphatases, is identified. 27037250 8 62 theme lipophilic 1492:1501 arg1 DLO 1529:1531 DLO 1529:1531 DLO 1529:1531 Therefore, a DLODP activity showing selectivity toward lipophilic diphosphodiesters such as DLO, and possessing properties distinct from other lipid phosphatases, is identified. 27037250 5 63 dep H 792:792 arg1 3 790:790 3 790:790 3 790:790 Polyprenyl diphosphates inhibit [(3)H]OSP release from [(3)H]DLO, the length of their alkyl chains correlating positively with inhibition potency. 27037250 1 64 theme Oligosaccharyl 195:208 arg1 OSPs 222:225 OSPs 222:225 OSPs 222:225 Oligosaccharyl phosphates (OSPs) are hydrolyzed from oligosaccharide-diphosphodolichol (DLO) during protein N-glycosylation by an uncharacterized process. 27037250 1 64 theme Oligosaccharyl 195:208 arg1 phosphates 210:219 Oligosaccharyl phosphates 195:219 Oligosaccharyl phosphates (OSPs) 195:226 Oligosaccharyl phosphates (OSPs) are hydrolyzed from oligosaccharide-diphosphodolichol (DLO) during protein N-glycosylation by an uncharacterized process. 27037250 7 65 theme liver 1105:1109 arg1 homogenates 1111:1121 liver homogenates 1105:1121 liver homogenates 1105:1121 During subcellular fractionation of liver homogenates, DLODP codistributes with microsomal markers, and density gradient centrifugation revealed that the distribution of DLODP is closer to that of Golgi apparatus-situated UDP-galactose glycoprotein galactosyltransferase than those of dolichyl-P-dependent glycosyltransferases required for DLO biosynthesis in the ER. 27037250 8 66 theme other 1574:1578 arg1 phosphatases 1586:1597 other lipid phosphatases 1574:1597 other lipid phosphatases 1574:1597 Therefore, a DLODP activity showing selectivity toward lipophilic diphosphodiesters such as DLO, and possessing properties distinct from other lipid phosphatases, is identified. 26205349 10 0 from signals 1752:1758 arg1 gonadotropes 1763:1774 gonadotropes 1763:1774 gonadotropes in the pars distalis of the pituitary 1763:1812 In situ hybridization of the mRNAs gave positive signals in gonadotropes in the pars distalis of the pituitary, which exhibited seasonal variation in staining intensity and numbers. 26205349 9 1 theme transcript 1547:1556 arg1 low 1572:1574 low 1572:1574 low 1572:1574 In the sexually quiescent phase, the transcript expression is low while in the recrudescent phase, the expressions are differential, high, and varied with regard to sex and reproductive phase. 26205349 9 1 theme transcript 1547:1556 arg1 expression 1558:1567 the transcript expression 1543:1567 the transcript expression 1543:1567 In the sexually quiescent phase, the transcript expression is low while in the recrudescent phase, the expressions are differential, high, and varied with regard to sex and reproductive phase. 26205349 5 2 theme glycosylation 998:1010 arg1 site 1012:1015 a single glycosylation site 989:1015 a single glycosylation site between Cys 3 and Cys 4 989:1039 In contrast, FSHβ has 13 cysteines, 1 additional over the conserved 12 cysteines of other vertebrates, and a single glycosylation site between Cys 3 and Cys 4. 26205349 0 3 theme seasonal 153:160 arg1 expression 162:171 seasonal expression 153:171 seasonal expression 153:171 Molecular cloning and characterization of the gonadotropin subunits GPα, FSHβ, and LHβ genes in the stinging catfish Heteropneustes fossilis: phylogeny, seasonal expression and pituitary localization. 26205349 0 3 theme seasonal 153:160 arg1 cloning 10:16 Molecular cloning 0:16 Molecular cloning 0:16 Molecular cloning and characterization of the gonadotropin subunits GPα, FSHβ, and LHβ genes in the stinging catfish Heteropneustes fossilis: phylogeny, seasonal expression and pituitary localization. 26205349 10 4 from gonadotropes 1763:1774 arg1 distalis 1788:1795 the pars distalis 1779:1795 the pars distalis of the pituitary 1779:1812 In situ hybridization of the mRNAs gave positive signals in gonadotropes in the pars distalis of the pituitary, which exhibited seasonal variation in staining intensity and numbers. 26205349 4 5 theme glycosylation 787:799 arg1 sites 801:805 2 N-linked glycosylation sites 776:805 2 N-linked glycosylation sites 776:805 GPα has 10 cysteines with 2 N-linked glycosylation sites while LHβ contains 12 cysteines with a single N-linked glycosylation site. 26205349 6 6 theme gonadotropin 1149:1160 arg1 proteins 1170:1177 the respective gonadotropin subunit proteins 1134:1177 the respective gonadotropin subunit proteins of gnathostome vertebrates 1134:1204 Phylogenetic analyses of the deduced proteins confirm their homology and relationships with the respective gonadotropin subunit proteins of gnathostome vertebrates. 26205349 4 7 link N-linked 778:785 arg1 sites 801:805 2 N-linked glycosylation sites 776:805 2 N-linked glycosylation sites 776:805 GPα has 10 cysteines with 2 N-linked glycosylation sites while LHβ contains 12 cysteines with a single N-linked glycosylation site. 26205349 10 8 theme staining 1853:1860 arg1 intensity 1862:1870 staining intensity 1853:1870 staining intensity 1853:1870 In situ hybridization of the mRNAs gave positive signals in gonadotropes in the pars distalis of the pituitary, which exhibited seasonal variation in staining intensity and numbers. 26205349 4 9 gly glycosylation 787:799 arg2 sites 801:805 2 N-linked glycosylation sites 776:805 2 N-linked glycosylation sites 776:805 GPα has 10 cysteines with 2 N-linked glycosylation sites while LHβ contains 12 cysteines with a single N-linked glycosylation site. 26205349 4 9 gly glycosylation 787:799 arg2 2 776:776 2 776:776 2 776:776 GPα has 10 cysteines with 2 N-linked glycosylation sites while LHβ contains 12 cysteines with a single N-linked glycosylation site. 26205349 10 10 dep In 1703:1704 arg1 situ 1706:1709 situ 1706:1709 situ 1706:1709 In situ hybridization of the mRNAs gave positive signals in gonadotropes in the pars distalis of the pituitary, which exhibited seasonal variation in staining intensity and numbers. 26205349 0 11 theme catfish 109:115 arg1 fossilis 132:139 the stinging catfish Heteropneustes fossilis 96:139 the stinging catfish Heteropneustes fossilis 96:139 Molecular cloning and characterization of the gonadotropin subunits GPα, FSHβ, and LHβ genes in the stinging catfish Heteropneustes fossilis: phylogeny, seasonal expression and pituitary localization. 26205349 5 12 theme vertebrates 972:982 arg1 cysteines 953:961 the conserved 12 cysteines 936:961 the conserved 12 cysteines of other vertebrates 936:982 In contrast, FSHβ has 13 cysteines, 1 additional over the conserved 12 cysteines of other vertebrates, and a single glycosylation site between Cys 3 and Cys 4. 26205349 3 13 theme Full-length 586:596 arg1 proteins 726:733 92, 108, and 112 aminoacids long mature proteins 686:733 92, 108, and 112 aminoacids long mature proteins 686:733 Full-length cDNAs of GPα, FSHβ, and LHβ are 511 base pairs (bp), 659 bp and 660 bp long, and encode 92, 108, and 112 aminoacids long mature proteins, respectively. 26205349 3 13 theme Full-length 586:596 arg1 cDNAs 598:602 Full-length cDNAs 586:602 Full-length cDNAs of GPα, FSHβ, and LHβ 586:624 Full-length cDNAs of GPα, FSHβ, and LHβ are 511 base pairs (bp), 659 bp and 660 bp long, and encode 92, 108, and 112 aminoacids long mature proteins, respectively. 26205349 3 13 theme Full-length 586:596 arg1 pairs 639:643 511 base pairs 630:643 511 base pairs (bp) 630:648 Full-length cDNAs of GPα, FSHβ, and LHβ are 511 base pairs (bp), 659 bp and 660 bp long, and encode 92, 108, and 112 aminoacids long mature proteins, respectively. 26205349 9 14 from low 1572:1574 arg1 phase 1536:1540 the sexually quiescent phase 1513:1540 the sexually quiescent phase 1513:1540 In the sexually quiescent phase, the transcript expression is low while in the recrudescent phase, the expressions are differential, high, and varied with regard to sex and reproductive phase. 26205349 2 15 theme catfish 553:559 arg1 fossilis 576:583 the catfish Heteropneustes fossilis 549:583 the catfish Heteropneustes fossilis 549:583 In the present study, the subunit protein genes were cloned and characterized from the pituitary of the catfish Heteropneustes fossilis. 26205349 1 16 theme luteinizing 409:419 arg1 hormone 421:427 luteinizing hormone 409:427 luteinizing hormone beta subunit (LHβ) 409:446 Gonadotropins are heterodimeric glycoproteins secreted by the pituitary, and consist of a common glycoprotein hormone alpha (GPα) and the function-specific follicle-stimulating hormone beta subunit (FSHβ) or luteinizing hormone beta subunit (LHβ). 26205349 2 17 theme fossilis 576:583 arg1 pituitary 536:544 the pituitary 532:544 the pituitary of the catfish Heteropneustes fossilis 532:583 In the present study, the subunit protein genes were cloned and characterized from the pituitary of the catfish Heteropneustes fossilis. 26205349 3 18 theme long 714:717 arg1 cDNAs 598:602 Full-length cDNAs 586:602 Full-length cDNAs of GPα, FSHβ, and LHβ 586:624 Full-length cDNAs of GPα, FSHβ, and LHβ are 511 base pairs (bp), 659 bp and 660 bp long, and encode 92, 108, and 112 aminoacids long mature proteins, respectively. 26205349 3 18 theme long 714:717 arg1 proteins 726:733 92, 108, and 112 aminoacids long mature proteins 686:733 92, 108, and 112 aminoacids long mature proteins 686:733 Full-length cDNAs of GPα, FSHβ, and LHβ are 511 base pairs (bp), 659 bp and 660 bp long, and encode 92, 108, and 112 aminoacids long mature proteins, respectively. 26205349 1 19 theme hormone 421:427 arg1 LHβ 443:445 LHβ 443:445 LHβ 443:445 Gonadotropins are heterodimeric glycoproteins secreted by the pituitary, and consist of a common glycoprotein hormone alpha (GPα) and the function-specific follicle-stimulating hormone beta subunit (FSHβ) or luteinizing hormone beta subunit (LHβ). 26205349 1 19 theme hormone 421:427 arg1 subunit 434:440 luteinizing hormone beta subunit 409:440 luteinizing hormone beta subunit (LHβ) 409:446 Gonadotropins are heterodimeric glycoproteins secreted by the pituitary, and consist of a common glycoprotein hormone alpha (GPα) and the function-specific follicle-stimulating hormone beta subunit (FSHβ) or luteinizing hormone beta subunit (LHβ). 26205349 6 20 with homology 1102:1109 arg1 proteins 1170:1177 the respective gonadotropin subunit proteins 1134:1177 the respective gonadotropin subunit proteins of gnathostome vertebrates 1134:1204 Phylogenetic analyses of the deduced proteins confirm their homology and relationships with the respective gonadotropin subunit proteins of gnathostome vertebrates. 26205349 2 21 theme subunit 475:481 arg1 genes 491:495 the subunit protein genes 471:495 the subunit protein genes 471:495 In the present study, the subunit protein genes were cloned and characterized from the pituitary of the catfish Heteropneustes fossilis. 26205349 8 22 theme subunit 1390:1396 arg1 mRNAs 1398:1402 The subunit mRNAs 1386:1402 The subunit mRNAs 1386:1402 The subunit mRNAs show both seasonal and sex dimorphic variations especially in the expression of FSHβ and LHβ transcripts. 26205349 6 23 theme proteins 1079:1086 arg1 analyses 1055:1062 Phylogenetic analyses 1042:1062 Phylogenetic analyses of the deduced proteins 1042:1086 Phylogenetic analyses of the deduced proteins confirm their homology and relationships with the respective gonadotropin subunit proteins of gnathostome vertebrates. 26205349 6 24 with relationships 1115:1127 arg1 proteins 1170:1177 the respective gonadotropin subunit proteins 1134:1177 the respective gonadotropin subunit proteins of gnathostome vertebrates 1134:1204 Phylogenetic analyses of the deduced proteins confirm their homology and relationships with the respective gonadotropin subunit proteins of gnathostome vertebrates. 26205349 1 25 gly glycoproteins 233:245 arg1 Gonadotropins 201:213 Gonadotropins 201:213 Gonadotropins 201:213 Gonadotropins are heterodimeric glycoproteins secreted by the pituitary, and consist of a common glycoprotein hormone alpha (GPα) and the function-specific follicle-stimulating hormone beta subunit (FSHβ) or luteinizing hormone beta subunit (LHβ). 26205349 1 25 gly glycoproteins 233:245 arg1 glycoproteins 233:245 heterodimeric glycoproteins 219:245 heterodimeric glycoproteins secreted by the pituitary 219:271 Gonadotropins are heterodimeric glycoproteins secreted by the pituitary, and consist of a common glycoprotein hormone alpha (GPα) and the function-specific follicle-stimulating hormone beta subunit (FSHβ) or luteinizing hormone beta subunit (LHβ). 26205349 2 26 theme Heteropneustes 561:574 arg1 fossilis 576:583 the catfish Heteropneustes fossilis 549:583 the catfish Heteropneustes fossilis 549:583 In the present study, the subunit protein genes were cloned and characterized from the pituitary of the catfish Heteropneustes fossilis. 26205349 4 27 theme N-linked 853:860 arg1 site 876:879 a single N-linked glycosylation site 844:879 a single N-linked glycosylation site 844:879 GPα has 10 cysteines with 2 N-linked glycosylation sites while LHβ contains 12 cysteines with a single N-linked glycosylation site. 26205349 8 28 theme seasonal 1414:1421 arg1 variations 1441:1450 both seasonal and sex dimorphic variations 1409:1450 both seasonal and sex dimorphic variations 1409:1450 The subunit mRNAs show both seasonal and sex dimorphic variations especially in the expression of FSHβ and LHβ transcripts. 26205349 1 29 theme function-specific 339:355 arg1 hormone 378:384 the function-specific follicle-stimulating hormone 335:384 the function-specific follicle-stimulating hormone 335:384 Gonadotropins are heterodimeric glycoproteins secreted by the pituitary, and consist of a common glycoprotein hormone alpha (GPα) and the function-specific follicle-stimulating hormone beta subunit (FSHβ) or luteinizing hormone beta subunit (LHβ). 26205349 1 30 theme hormone 378:384 arg1 FSHβ 400:403 FSHβ 400:403 FSHβ 400:403 Gonadotropins are heterodimeric glycoproteins secreted by the pituitary, and consist of a common glycoprotein hormone alpha (GPα) and the function-specific follicle-stimulating hormone beta subunit (FSHβ) or luteinizing hormone beta subunit (LHβ). 26205349 1 30 theme hormone 378:384 arg1 subunit 391:397 a common glycoprotein hormone alpha (GPα) and the function-specific follicle-stimulating hormone beta subunit 289:397 a common glycoprotein hormone alpha (GPα) and the function-specific follicle-stimulating hormone beta subunit (FSHβ) 289:404 Gonadotropins are heterodimeric glycoproteins secreted by the pituitary, and consist of a common glycoprotein hormone alpha (GPα) and the function-specific follicle-stimulating hormone beta subunit (FSHβ) or luteinizing hormone beta subunit (LHβ). 26205349 9 31 theme reproductive 1683:1694 arg1 phase 1696:1700 reproductive phase 1683:1700 reproductive phase 1683:1700 In the sexually quiescent phase, the transcript expression is low while in the recrudescent phase, the expressions are differential, high, and varied with regard to sex and reproductive phase. 26205349 1 32 dep hormone 311:317 arg1 alpha 319:323 alpha (GPα) 319:329 alpha (GPα) 319:329 Gonadotropins are heterodimeric glycoproteins secreted by the pituitary, and consist of a common glycoprotein hormone alpha (GPα) and the function-specific follicle-stimulating hormone beta subunit (FSHβ) or luteinizing hormone beta subunit (LHβ). 26205349 0 33 theme Molecular 0:8 arg1 cloning 10:16 Molecular cloning 0:16 Molecular cloning 0:16 Molecular cloning and characterization of the gonadotropin subunits GPα, FSHβ, and LHβ genes in the stinging catfish Heteropneustes fossilis: phylogeny, seasonal expression and pituitary localization. 26205349 0 33 theme Molecular 0:8 arg1 localization 187:198 pituitary localization 177:198 pituitary localization 177:198 Molecular cloning and characterization of the gonadotropin subunits GPα, FSHβ, and LHβ genes in the stinging catfish Heteropneustes fossilis: phylogeny, seasonal expression and pituitary localization. 26205349 0 33 theme Molecular 0:8 arg1 expression 162:171 seasonal expression 153:171 seasonal expression 153:171 Molecular cloning and characterization of the gonadotropin subunits GPα, FSHβ, and LHβ genes in the stinging catfish Heteropneustes fossilis: phylogeny, seasonal expression and pituitary localization. 26205349 7 34 theme semi-quantitative 1237:1253 arg1 RT-PCR 1255:1260 semi-quantitative RT-PCR 1237:1260 semi-quantitative RT-PCR 1237:1260 Tissue expression analysis by semi-quantitative RT-PCR shows that GPα mRNA is expressed only in the pituitary while both FSHβ and LHβ mRNA are expressed in extra-pituitary sites. 26205349 2 35 theme present 456:462 arg1 study 464:468 the present study 452:468 the present study 452:468 In the present study, the subunit protein genes were cloned and characterized from the pituitary of the catfish Heteropneustes fossilis. 26205349 3 36 theme LHβ 622:624 arg1 proteins 726:733 92, 108, and 112 aminoacids long mature proteins 686:733 92, 108, and 112 aminoacids long mature proteins 686:733 Full-length cDNAs of GPα, FSHβ, and LHβ are 511 base pairs (bp), 659 bp and 660 bp long, and encode 92, 108, and 112 aminoacids long mature proteins, respectively. 26205349 3 36 theme LHβ 622:624 arg1 cDNAs 598:602 Full-length cDNAs 586:602 Full-length cDNAs of GPα, FSHβ, and LHβ 586:624 Full-length cDNAs of GPα, FSHβ, and LHβ are 511 base pairs (bp), 659 bp and 660 bp long, and encode 92, 108, and 112 aminoacids long mature proteins, respectively. 26205349 3 36 theme LHβ 622:624 arg1 pairs 639:643 511 base pairs 630:643 511 base pairs (bp) 630:648 Full-length cDNAs of GPα, FSHβ, and LHβ are 511 base pairs (bp), 659 bp and 660 bp long, and encode 92, 108, and 112 aminoacids long mature proteins, respectively. 26205349 1 37 theme glycoprotein 298:309 arg1 hormone 311:317 a common glycoprotein hormone alpha (GPα) and the function-specific follicle-stimulating hormone 289:384 hormone 311:317 Gonadotropins are heterodimeric glycoproteins secreted by the pituitary, and consist of a common glycoprotein hormone alpha (GPα) and the function-specific follicle-stimulating hormone beta subunit (FSHβ) or luteinizing hormone beta subunit (LHβ). 26205349 7 38 theme Tissue 1207:1212 arg1 analysis 1225:1232 Tissue expression analysis 1207:1232 Tissue expression analysis by semi-quantitative RT-PCR 1207:1260 Tissue expression analysis by semi-quantitative RT-PCR shows that GPα mRNA is expressed only in the pituitary while both FSHβ and LHβ mRNA are expressed in extra-pituitary sites. 26205349 8 39 theme FSHβ 1484:1487 arg1 transcripts 1497:1507 FSHβ and LHβ transcripts 1484:1507 FSHβ and LHβ transcripts 1484:1507 The subunit mRNAs show both seasonal and sex dimorphic variations especially in the expression of FSHβ and LHβ transcripts. 26205349 10 40 theme mRNAs 1732:1736 arg1 hybridization 1711:1723 In situ hybridization 1703:1723 In situ hybridization of the mRNAs 1703:1736 In situ hybridization of the mRNAs gave positive signals in gonadotropes in the pars distalis of the pituitary, which exhibited seasonal variation in staining intensity and numbers. 26205349 10 41 theme positive 1743:1750 arg1 signals 1752:1758 positive signals 1743:1758 positive signals 1743:1758 In situ hybridization of the mRNAs gave positive signals in gonadotropes in the pars distalis of the pituitary, which exhibited seasonal variation in staining intensity and numbers. 26205349 0 42 theme gonadotropin 46:57 arg1 FSHβ 73:76 FSHβ 73:76 FSHβ 73:76 Molecular cloning and characterization of the gonadotropin subunits GPα, FSHβ, and LHβ genes in the stinging catfish Heteropneustes fossilis: phylogeny, seasonal expression and pituitary localization. 26205349 0 42 theme gonadotropin 46:57 arg1 GPα 68:70 GPα 68:70 GPα 68:70 Molecular cloning and characterization of the gonadotropin subunits GPα, FSHβ, and LHβ genes in the stinging catfish Heteropneustes fossilis: phylogeny, seasonal expression and pituitary localization. 26205349 0 42 theme gonadotropin 46:57 arg1 subunits 59:66 the gonadotropin subunits GPα, FSHβ, and LHβ genes 42:91 the gonadotropin subunits GPα, FSHβ, and LHβ genes in the stinging catfish Heteropneustes fossilis 42:139 Molecular cloning and characterization of the gonadotropin subunits GPα, FSHβ, and LHβ genes in the stinging catfish Heteropneustes fossilis: phylogeny, seasonal expression and pituitary localization. 26205349 8 43 theme LHβ 1493:1495 arg1 transcripts 1497:1507 FSHβ and LHβ transcripts 1484:1507 FSHβ and LHβ transcripts 1484:1507 The subunit mRNAs show both seasonal and sex dimorphic variations especially in the expression of FSHβ and LHβ transcripts. 26205349 4 44 link N-linked 853:860 arg1 site 876:879 a single N-linked glycosylation site 844:879 a single N-linked glycosylation site 844:879 GPα has 10 cysteines with 2 N-linked glycosylation sites while LHβ contains 12 cysteines with a single N-linked glycosylation site. 26205349 1 45 theme heterodimeric 219:231 arg1 Gonadotropins 201:213 Gonadotropins 201:213 Gonadotropins 201:213 Gonadotropins are heterodimeric glycoproteins secreted by the pituitary, and consist of a common glycoprotein hormone alpha (GPα) and the function-specific follicle-stimulating hormone beta subunit (FSHβ) or luteinizing hormone beta subunit (LHβ). 26205349 1 45 theme heterodimeric 219:231 arg1 glycoproteins 233:245 heterodimeric glycoproteins 219:245 heterodimeric glycoproteins secreted by the pituitary 219:271 Gonadotropins are heterodimeric glycoproteins secreted by the pituitary, and consist of a common glycoprotein hormone alpha (GPα) and the function-specific follicle-stimulating hormone beta subunit (FSHβ) or luteinizing hormone beta subunit (LHβ). 26205349 6 46 theme Phylogenetic 1042:1053 arg1 analyses 1055:1062 Phylogenetic analyses 1042:1062 Phylogenetic analyses of the deduced proteins 1042:1086 Phylogenetic analyses of the deduced proteins confirm their homology and relationships with the respective gonadotropin subunit proteins of gnathostome vertebrates. 26205349 9 47 from differential 1629:1640 arg1 phase 1602:1606 the recrudescent phase 1585:1606 the recrudescent phase 1585:1606 In the sexually quiescent phase, the transcript expression is low while in the recrudescent phase, the expressions are differential, high, and varied with regard to sex and reproductive phase. 26205349 6 48 theme vertebrates 1194:1204 arg1 proteins 1170:1177 the respective gonadotropin subunit proteins 1134:1177 the respective gonadotropin subunit proteins of gnathostome vertebrates 1134:1204 Phylogenetic analyses of the deduced proteins confirm their homology and relationships with the respective gonadotropin subunit proteins of gnathostome vertebrates. 26205349 5 49 contain has 900:902 arg1 FSHβ 895:898 FSHβ 895:898 FSHβ 895:898 In contrast, FSHβ has 13 cysteines, 1 additional over the conserved 12 cysteines of other vertebrates, and a single glycosylation site between Cys 3 and Cys 4. 26205349 5 49 contain has 900:902 arg2 additional 920:929 additional 920:929 additional 920:929 In contrast, FSHβ has 13 cysteines, 1 additional over the conserved 12 cysteines of other vertebrates, and a single glycosylation site between Cys 3 and Cys 4. 26205349 5 49 contain has 900:902 arg2 cysteines 907:915 13 cysteines 904:915 13 cysteines 904:915 In contrast, FSHβ has 13 cysteines, 1 additional over the conserved 12 cysteines of other vertebrates, and a single glycosylation site between Cys 3 and Cys 4. 26205349 5 49 contain has 900:902 arg2 site 1012:1015 a single glycosylation site 989:1015 a single glycosylation site between Cys 3 and Cys 4 989:1039 In contrast, FSHβ has 13 cysteines, 1 additional over the conserved 12 cysteines of other vertebrates, and a single glycosylation site between Cys 3 and Cys 4. 26205349 10 50 theme pars 1783:1786 arg1 distalis 1788:1795 the pars distalis 1779:1795 the pars distalis of the pituitary 1779:1812 In situ hybridization of the mRNAs gave positive signals in gonadotropes in the pars distalis of the pituitary, which exhibited seasonal variation in staining intensity and numbers. 26205349 0 51 theme pituitary 177:185 arg1 cloning 10:16 Molecular cloning 0:16 Molecular cloning 0:16 Molecular cloning and characterization of the gonadotropin subunits GPα, FSHβ, and LHβ genes in the stinging catfish Heteropneustes fossilis: phylogeny, seasonal expression and pituitary localization. 26205349 0 51 theme pituitary 177:185 arg1 localization 187:198 pituitary localization 177:198 pituitary localization 177:198 Molecular cloning and characterization of the gonadotropin subunits GPα, FSHβ, and LHβ genes in the stinging catfish Heteropneustes fossilis: phylogeny, seasonal expression and pituitary localization. 26205349 7 52 theme extra-pituitary 1363:1377 arg1 sites 1379:1383 extra-pituitary sites 1363:1383 extra-pituitary sites 1363:1383 Tissue expression analysis by semi-quantitative RT-PCR shows that GPα mRNA is expressed only in the pituitary while both FSHβ and LHβ mRNA are expressed in extra-pituitary sites. 26205349 4 53 theme N-linked 778:785 arg1 sites 801:805 2 N-linked glycosylation sites 776:805 2 N-linked glycosylation sites 776:805 GPα has 10 cysteines with 2 N-linked glycosylation sites while LHβ contains 12 cysteines with a single N-linked glycosylation site. 26205349 0 54 from fossilis 132:139 arg1 characterization 22:37 characterization 22:37 characterization 22:37 Molecular cloning and characterization of the gonadotropin subunits GPα, FSHβ, and LHβ genes in the stinging catfish Heteropneustes fossilis: phylogeny, seasonal expression and pituitary localization. 26205349 0 54 from fossilis 132:139 arg1 cloning 10:16 Molecular cloning 0:16 Molecular cloning 0:16 Molecular cloning and characterization of the gonadotropin subunits GPα, FSHβ, and LHβ genes in the stinging catfish Heteropneustes fossilis: phylogeny, seasonal expression and pituitary localization. 26205349 0 54 from fossilis 132:139 arg1 localization 187:198 pituitary localization 177:198 pituitary localization 177:198 Molecular cloning and characterization of the gonadotropin subunits GPα, FSHβ, and LHβ genes in the stinging catfish Heteropneustes fossilis: phylogeny, seasonal expression and pituitary localization. 26205349 0 54 from fossilis 132:139 arg1 expression 162:171 seasonal expression 153:171 seasonal expression 153:171 Molecular cloning and characterization of the gonadotropin subunits GPα, FSHβ, and LHβ genes in the stinging catfish Heteropneustes fossilis: phylogeny, seasonal expression and pituitary localization. 26205349 6 55 theme subunit 1162:1168 arg1 proteins 1170:1177 the respective gonadotropin subunit proteins 1134:1177 the respective gonadotropin subunit proteins of gnathostome vertebrates 1134:1204 Phylogenetic analyses of the deduced proteins confirm their homology and relationships with the respective gonadotropin subunit proteins of gnathostome vertebrates. 26205349 7 56 theme LHβ 1337:1339 arg1 mRNA 1341:1344 LHβ mRNA 1337:1344 LHβ mRNA 1337:1344 Tissue expression analysis by semi-quantitative RT-PCR shows that GPα mRNA is expressed only in the pituitary while both FSHβ and LHβ mRNA are expressed in extra-pituitary sites. 26205349 10 57 theme pituitary 1804:1812 arg1 distalis 1788:1795 the pars distalis 1779:1795 the pars distalis of the pituitary 1779:1812 In situ hybridization of the mRNAs gave positive signals in gonadotropes in the pars distalis of the pituitary, which exhibited seasonal variation in staining intensity and numbers. 26205349 6 58 theme respective 1138:1147 arg1 proteins 1170:1177 the respective gonadotropin subunit proteins 1134:1177 the respective gonadotropin subunit proteins of gnathostome vertebrates 1134:1204 Phylogenetic analyses of the deduced proteins confirm their homology and relationships with the respective gonadotropin subunit proteins of gnathostome vertebrates. 26205349 9 59 theme recrudescent 1589:1600 arg1 phase 1602:1606 the recrudescent phase 1585:1606 the recrudescent phase 1585:1606 In the sexually quiescent phase, the transcript expression is low while in the recrudescent phase, the expressions are differential, high, and varied with regard to sex and reproductive phase. 26205349 0 60 theme stinging 100:107 arg1 fossilis 132:139 the stinging catfish Heteropneustes fossilis 96:139 the stinging catfish Heteropneustes fossilis 96:139 Molecular cloning and characterization of the gonadotropin subunits GPα, FSHβ, and LHβ genes in the stinging catfish Heteropneustes fossilis: phylogeny, seasonal expression and pituitary localization. 26205349 5 61 gly glycosylation 998:1010 arg2 site 1012:1015 a single glycosylation site 989:1015 a single glycosylation site between Cys 3 and Cys 4 989:1039 In contrast, FSHβ has 13 cysteines, 1 additional over the conserved 12 cysteines of other vertebrates, and a single glycosylation site between Cys 3 and Cys 4. 26205349 10 62 theme seasonal 1831:1838 arg1 variation 1840:1848 seasonal variation 1831:1848 seasonal variation in staining intensity and numbers 1831:1882 In situ hybridization of the mRNAs gave positive signals in gonadotropes in the pars distalis of the pituitary, which exhibited seasonal variation in staining intensity and numbers. 26205349 0 63 theme Heteropneustes 117:130 arg1 fossilis 132:139 the stinging catfish Heteropneustes fossilis 96:139 the stinging catfish Heteropneustes fossilis 96:139 Molecular cloning and characterization of the gonadotropin subunits GPα, FSHβ, and LHβ genes in the stinging catfish Heteropneustes fossilis: phylogeny, seasonal expression and pituitary localization. 26205349 5 64 theme other 966:970 arg1 vertebrates 972:982 other vertebrates 966:982 other vertebrates 966:982 In contrast, FSHβ has 13 cysteines, 1 additional over the conserved 12 cysteines of other vertebrates, and a single glycosylation site between Cys 3 and Cys 4. 26205349 10 65 theme In 1703:1704 arg1 hybridization 1711:1723 In situ hybridization 1703:1723 In situ hybridization of the mRNAs 1703:1736 In situ hybridization of the mRNAs gave positive signals in gonadotropes in the pars distalis of the pituitary, which exhibited seasonal variation in staining intensity and numbers. 26205349 5 66 theme conserved 940:948 arg1 cysteines 953:961 the conserved 12 cysteines 936:961 the conserved 12 cysteines of other vertebrates 936:982 In contrast, FSHβ has 13 cysteines, 1 additional over the conserved 12 cysteines of other vertebrates, and a single glycosylation site between Cys 3 and Cys 4. 26205349 3 67 theme GPα 607:609 arg1 proteins 726:733 92, 108, and 112 aminoacids long mature proteins 686:733 92, 108, and 112 aminoacids long mature proteins 686:733 Full-length cDNAs of GPα, FSHβ, and LHβ are 511 base pairs (bp), 659 bp and 660 bp long, and encode 92, 108, and 112 aminoacids long mature proteins, respectively. 26205349 3 67 theme GPα 607:609 arg1 cDNAs 598:602 Full-length cDNAs 586:602 Full-length cDNAs of GPα, FSHβ, and LHβ 586:624 Full-length cDNAs of GPα, FSHβ, and LHβ are 511 base pairs (bp), 659 bp and 660 bp long, and encode 92, 108, and 112 aminoacids long mature proteins, respectively. 26205349 3 67 theme GPα 607:609 arg1 pairs 639:643 511 base pairs 630:643 511 base pairs (bp) 630:648 Full-length cDNAs of GPα, FSHβ, and LHβ are 511 base pairs (bp), 659 bp and 660 bp long, and encode 92, 108, and 112 aminoacids long mature proteins, respectively. 26205349 3 68 theme mature 719:724 arg1 cDNAs 598:602 Full-length cDNAs 586:602 Full-length cDNAs of GPα, FSHβ, and LHβ 586:624 Full-length cDNAs of GPα, FSHβ, and LHβ are 511 base pairs (bp), 659 bp and 660 bp long, and encode 92, 108, and 112 aminoacids long mature proteins, respectively. 26205349 3 68 theme mature 719:724 arg1 proteins 726:733 92, 108, and 112 aminoacids long mature proteins 686:733 92, 108, and 112 aminoacids long mature proteins 686:733 Full-length cDNAs of GPα, FSHβ, and LHβ are 511 base pairs (bp), 659 bp and 660 bp long, and encode 92, 108, and 112 aminoacids long mature proteins, respectively. 26205349 1 69 theme beta 429:432 arg1 LHβ 443:445 LHβ 443:445 LHβ 443:445 Gonadotropins are heterodimeric glycoproteins secreted by the pituitary, and consist of a common glycoprotein hormone alpha (GPα) and the function-specific follicle-stimulating hormone beta subunit (FSHβ) or luteinizing hormone beta subunit (LHβ). 26205349 1 69 theme beta 429:432 arg1 subunit 434:440 luteinizing hormone beta subunit 409:440 luteinizing hormone beta subunit (LHβ) 409:446 Gonadotropins are heterodimeric glycoproteins secreted by the pituitary, and consist of a common glycoprotein hormone alpha (GPα) and the function-specific follicle-stimulating hormone beta subunit (FSHβ) or luteinizing hormone beta subunit (LHβ). 26205349 1 70 gly glycoprotein 298:309 arg1 glycoprotein 298:309 a common glycoprotein hormone alpha (GPα) and the function-specific follicle-stimulating hormone 289:384 glycoprotein 298:309 Gonadotropins are heterodimeric glycoproteins secreted by the pituitary, and consist of a common glycoprotein hormone alpha (GPα) and the function-specific follicle-stimulating hormone beta subunit (FSHβ) or luteinizing hormone beta subunit (LHβ). 26205349 4 71 contain has 754:756 arg1 GPα 750:752 GPα 750:752 GPα 750:752 GPα has 10 cysteines with 2 N-linked glycosylation sites while LHβ contains 12 cysteines with a single N-linked glycosylation site. 26205349 4 71 contain has 754:756 arg2 cysteines 761:769 10 cysteines 758:769 10 cysteines 758:769 GPα has 10 cysteines with 2 N-linked glycosylation sites while LHβ contains 12 cysteines with a single N-linked glycosylation site. 26205349 0 72 from characterization 22:37 arg1 fossilis 132:139 the stinging catfish Heteropneustes fossilis 96:139 the stinging catfish Heteropneustes fossilis 96:139 Molecular cloning and characterization of the gonadotropin subunits GPα, FSHβ, and LHβ genes in the stinging catfish Heteropneustes fossilis: phylogeny, seasonal expression and pituitary localization. 26205349 7 73 theme GPα 1273:1275 arg1 mRNA 1277:1280 GPα mRNA 1273:1280 GPα mRNA 1273:1280 Tissue expression analysis by semi-quantitative RT-PCR shows that GPα mRNA is expressed only in the pituitary while both FSHβ and LHβ mRNA are expressed in extra-pituitary sites. 26205349 10 74 from variation 1840:1848 arg1 numbers 1876:1882 numbers 1876:1882 numbers 1876:1882 In situ hybridization of the mRNAs gave positive signals in gonadotropes in the pars distalis of the pituitary, which exhibited seasonal variation in staining intensity and numbers. 26205349 10 74 from variation 1840:1848 arg1 intensity 1862:1870 staining intensity 1853:1870 staining intensity 1853:1870 In situ hybridization of the mRNAs gave positive signals in gonadotropes in the pars distalis of the pituitary, which exhibited seasonal variation in staining intensity and numbers. 26205349 8 75 theme dimorphic 1431:1439 arg1 variations 1441:1450 both seasonal and sex dimorphic variations 1409:1450 both seasonal and sex dimorphic variations 1409:1450 The subunit mRNAs show both seasonal and sex dimorphic variations especially in the expression of FSHβ and LHβ transcripts. 26205349 0 76 from cloning 10:16 arg1 fossilis 132:139 the stinging catfish Heteropneustes fossilis 96:139 the stinging catfish Heteropneustes fossilis 96:139 Molecular cloning and characterization of the gonadotropin subunits GPα, FSHβ, and LHβ genes in the stinging catfish Heteropneustes fossilis: phylogeny, seasonal expression and pituitary localization. 26205349 0 77 theme LHβ 83:85 arg1 genes 87:91 LHβ genes 83:91 LHβ genes 83:91 Molecular cloning and characterization of the gonadotropin subunits GPα, FSHβ, and LHβ genes in the stinging catfish Heteropneustes fossilis: phylogeny, seasonal expression and pituitary localization. 26205349 9 78 from phase 1602:1606 arg1 differential 1629:1640 differential 1629:1640 differential 1629:1640 In the sexually quiescent phase, the transcript expression is low while in the recrudescent phase, the expressions are differential, high, and varied with regard to sex and reproductive phase. 26205349 9 78 from phase 1602:1606 arg1 expressions 1613:1623 the expressions 1609:1623 the expressions 1609:1623 In the sexually quiescent phase, the transcript expression is low while in the recrudescent phase, the expressions are differential, high, and varied with regard to sex and reproductive phase. 26205349 4 79 theme single 846:851 arg1 site 876:879 a single N-linked glycosylation site 844:879 a single N-linked glycosylation site 844:879 GPα has 10 cysteines with 2 N-linked glycosylation sites while LHβ contains 12 cysteines with a single N-linked glycosylation site. 26205349 0 80 from subunits 59:66 arg1 fossilis 132:139 the stinging catfish Heteropneustes fossilis 96:139 the stinging catfish Heteropneustes fossilis 96:139 Molecular cloning and characterization of the gonadotropin subunits GPα, FSHβ, and LHβ genes in the stinging catfish Heteropneustes fossilis: phylogeny, seasonal expression and pituitary localization. 26205349 1 81 theme follicle-stimulating 357:376 arg1 hormone 378:384 the function-specific follicle-stimulating hormone 335:384 the function-specific follicle-stimulating hormone 335:384 Gonadotropins are heterodimeric glycoproteins secreted by the pituitary, and consist of a common glycoprotein hormone alpha (GPα) and the function-specific follicle-stimulating hormone beta subunit (FSHβ) or luteinizing hormone beta subunit (LHβ). 26205349 4 82 contain contains 817:824 arg1 LHβ 813:815 LHβ 813:815 LHβ 813:815 GPα has 10 cysteines with 2 N-linked glycosylation sites while LHβ contains 12 cysteines with a single N-linked glycosylation site. 26205349 4 82 contain contains 817:824 arg2 cysteines 829:837 12 cysteines 826:837 12 cysteines 826:837 GPα has 10 cysteines with 2 N-linked glycosylation sites while LHβ contains 12 cysteines with a single N-linked glycosylation site. 26205349 2 83 theme protein 483:489 arg1 genes 491:495 the subunit protein genes 471:495 the subunit protein genes 471:495 In the present study, the subunit protein genes were cloned and characterized from the pituitary of the catfish Heteropneustes fossilis. 26205349 1 84 theme beta 386:389 arg1 FSHβ 400:403 FSHβ 400:403 FSHβ 400:403 Gonadotropins are heterodimeric glycoproteins secreted by the pituitary, and consist of a common glycoprotein hormone alpha (GPα) and the function-specific follicle-stimulating hormone beta subunit (FSHβ) or luteinizing hormone beta subunit (LHβ). 26205349 1 84 theme beta 386:389 arg1 subunit 391:397 a common glycoprotein hormone alpha (GPα) and the function-specific follicle-stimulating hormone beta subunit 289:397 a common glycoprotein hormone alpha (GPα) and the function-specific follicle-stimulating hormone beta subunit (FSHβ) 289:404 Gonadotropins are heterodimeric glycoproteins secreted by the pituitary, and consist of a common glycoprotein hormone alpha (GPα) and the function-specific follicle-stimulating hormone beta subunit (FSHβ) or luteinizing hormone beta subunit (LHβ). 26205349 9 85 from phase 1536:1540 arg1 low 1572:1574 low 1572:1574 low 1572:1574 In the sexually quiescent phase, the transcript expression is low while in the recrudescent phase, the expressions are differential, high, and varied with regard to sex and reproductive phase. 26205349 9 85 from phase 1536:1540 arg1 expression 1558:1567 the transcript expression 1543:1567 the transcript expression 1543:1567 In the sexually quiescent phase, the transcript expression is low while in the recrudescent phase, the expressions are differential, high, and varied with regard to sex and reproductive phase. 26205349 4 86 gly glycosylation 862:874 arg2 site 876:879 a single N-linked glycosylation site 844:879 a single N-linked glycosylation site 844:879 GPα has 10 cysteines with 2 N-linked glycosylation sites while LHβ contains 12 cysteines with a single N-linked glycosylation site. 26205349 7 87 theme expression 1214:1223 arg1 analysis 1225:1232 Tissue expression analysis 1207:1232 Tissue expression analysis by semi-quantitative RT-PCR 1207:1260 Tissue expression analysis by semi-quantitative RT-PCR shows that GPα mRNA is expressed only in the pituitary while both FSHβ and LHβ mRNA are expressed in extra-pituitary sites. 26205349 1 88 theme common 291:296 arg1 hormone 311:317 a common glycoprotein hormone alpha (GPα) and the function-specific follicle-stimulating hormone 289:384 hormone 311:317 Gonadotropins are heterodimeric glycoproteins secreted by the pituitary, and consist of a common glycoprotein hormone alpha (GPα) and the function-specific follicle-stimulating hormone beta subunit (FSHβ) or luteinizing hormone beta subunit (LHβ). 26205349 0 89 dep subunits 59:66 arg1 FSHβ 73:76 FSHβ 73:76 FSHβ 73:76 Molecular cloning and characterization of the gonadotropin subunits GPα, FSHβ, and LHβ genes in the stinging catfish Heteropneustes fossilis: phylogeny, seasonal expression and pituitary localization. 26205349 0 89 dep subunits 59:66 arg1 GPα 68:70 GPα 68:70 GPα 68:70 Molecular cloning and characterization of the gonadotropin subunits GPα, FSHβ, and LHβ genes in the stinging catfish Heteropneustes fossilis: phylogeny, seasonal expression and pituitary localization. 26205349 0 89 dep subunits 59:66 arg1 genes 87:91 LHβ genes 83:91 LHβ genes 83:91 Molecular cloning and characterization of the gonadotropin subunits GPα, FSHβ, and LHβ genes in the stinging catfish Heteropneustes fossilis: phylogeny, seasonal expression and pituitary localization. 26205349 0 89 dep subunits 59:66 arg1 subunits 59:66 the gonadotropin subunits GPα, FSHβ, and LHβ genes 42:91 the gonadotropin subunits GPα, FSHβ, and LHβ genes in the stinging catfish Heteropneustes fossilis 42:139 Molecular cloning and characterization of the gonadotropin subunits GPα, FSHβ, and LHβ genes in the stinging catfish Heteropneustes fossilis: phylogeny, seasonal expression and pituitary localization. 26205349 6 90 theme deduced 1071:1077 arg1 proteins 1079:1086 the deduced proteins 1067:1086 the deduced proteins 1067:1086 Phylogenetic analyses of the deduced proteins confirm their homology and relationships with the respective gonadotropin subunit proteins of gnathostome vertebrates. 26205349 3 91 theme FSHβ 612:615 arg1 proteins 726:733 92, 108, and 112 aminoacids long mature proteins 686:733 92, 108, and 112 aminoacids long mature proteins 686:733 Full-length cDNAs of GPα, FSHβ, and LHβ are 511 base pairs (bp), 659 bp and 660 bp long, and encode 92, 108, and 112 aminoacids long mature proteins, respectively. 26205349 3 91 theme FSHβ 612:615 arg1 cDNAs 598:602 Full-length cDNAs 586:602 Full-length cDNAs of GPα, FSHβ, and LHβ 586:624 Full-length cDNAs of GPα, FSHβ, and LHβ are 511 base pairs (bp), 659 bp and 660 bp long, and encode 92, 108, and 112 aminoacids long mature proteins, respectively. 26205349 3 91 theme FSHβ 612:615 arg1 pairs 639:643 511 base pairs 630:643 511 base pairs (bp) 630:648 Full-length cDNAs of GPα, FSHβ, and LHβ are 511 base pairs (bp), 659 bp and 660 bp long, and encode 92, 108, and 112 aminoacids long mature proteins, respectively. 26205349 4 92 theme glycosylation 862:874 arg1 site 876:879 a single N-linked glycosylation site 844:879 a single N-linked glycosylation site 844:879 GPα has 10 cysteines with 2 N-linked glycosylation sites while LHβ contains 12 cysteines with a single N-linked glycosylation site. 26205349 0 93 theme subunits 59:66 arg1 characterization 22:37 characterization 22:37 characterization 22:37 Molecular cloning and characterization of the gonadotropin subunits GPα, FSHβ, and LHβ genes in the stinging catfish Heteropneustes fossilis: phylogeny, seasonal expression and pituitary localization. 26205349 0 93 theme subunits 59:66 arg1 cloning 10:16 Molecular cloning 0:16 Molecular cloning 0:16 Molecular cloning and characterization of the gonadotropin subunits GPα, FSHβ, and LHβ genes in the stinging catfish Heteropneustes fossilis: phylogeny, seasonal expression and pituitary localization. 26205349 0 93 theme subunits 59:66 arg1 localization 187:198 pituitary localization 177:198 pituitary localization 177:198 Molecular cloning and characterization of the gonadotropin subunits GPα, FSHβ, and LHβ genes in the stinging catfish Heteropneustes fossilis: phylogeny, seasonal expression and pituitary localization. 26205349 0 93 theme subunits 59:66 arg1 expression 162:171 seasonal expression 153:171 seasonal expression 153:171 Molecular cloning and characterization of the gonadotropin subunits GPα, FSHβ, and LHβ genes in the stinging catfish Heteropneustes fossilis: phylogeny, seasonal expression and pituitary localization. 26205349 1 94 theme hormone 311:317 arg1 FSHβ 400:403 FSHβ 400:403 FSHβ 400:403 Gonadotropins are heterodimeric glycoproteins secreted by the pituitary, and consist of a common glycoprotein hormone alpha (GPα) and the function-specific follicle-stimulating hormone beta subunit (FSHβ) or luteinizing hormone beta subunit (LHβ). 26205349 1 94 theme hormone 311:317 arg1 subunit 391:397 a common glycoprotein hormone alpha (GPα) and the function-specific follicle-stimulating hormone beta subunit 289:397 a common glycoprotein hormone alpha (GPα) and the function-specific follicle-stimulating hormone beta subunit (FSHβ) 289:404 Gonadotropins are heterodimeric glycoproteins secreted by the pituitary, and consist of a common glycoprotein hormone alpha (GPα) and the function-specific follicle-stimulating hormone beta subunit (FSHβ) or luteinizing hormone beta subunit (LHβ). 26205349 5 95 theme single 991:996 arg1 site 1012:1015 a single glycosylation site 989:1015 a single glycosylation site between Cys 3 and Cys 4 989:1039 In contrast, FSHβ has 13 cysteines, 1 additional over the conserved 12 cysteines of other vertebrates, and a single glycosylation site between Cys 3 and Cys 4. 26205349 8 96 theme transcripts 1497:1507 arg1 expression 1470:1479 the expression 1466:1479 the expression of FSHβ and LHβ transcripts 1466:1507 The subunit mRNAs show both seasonal and sex dimorphic variations especially in the expression of FSHβ and LHβ transcripts. 26205349 3 97 theme base 634:637 arg1 long 669:672 long 669:672 long 669:672 Full-length cDNAs of GPα, FSHβ, and LHβ are 511 base pairs (bp), 659 bp and 660 bp long, and encode 92, 108, and 112 aminoacids long mature proteins, respectively. 26205349 3 97 theme base 634:637 arg1 cDNAs 598:602 Full-length cDNAs 586:602 Full-length cDNAs of GPα, FSHβ, and LHβ 586:624 Full-length cDNAs of GPα, FSHβ, and LHβ are 511 base pairs (bp), 659 bp and 660 bp long, and encode 92, 108, and 112 aminoacids long mature proteins, respectively. 26205349 3 97 theme base 634:637 arg1 bp 646:647 bp 646:647 bp 646:647 Full-length cDNAs of GPα, FSHβ, and LHβ are 511 base pairs (bp), 659 bp and 660 bp long, and encode 92, 108, and 112 aminoacids long mature proteins, respectively. 26205349 3 97 theme base 634:637 arg1 659 bp 651:656 659 bp 651:656 659 bp 651:656 Full-length cDNAs of GPα, FSHβ, and LHβ are 511 base pairs (bp), 659 bp and 660 bp long, and encode 92, 108, and 112 aminoacids long mature proteins, respectively. 26205349 3 97 theme base 634:637 arg1 pairs 639:643 511 base pairs 630:643 511 base pairs (bp) 630:648 Full-length cDNAs of GPα, FSHβ, and LHβ are 511 base pairs (bp), 659 bp and 660 bp long, and encode 92, 108, and 112 aminoacids long mature proteins, respectively. 26205349 6 98 theme gnathostome 1182:1192 arg1 vertebrates 1194:1204 gnathostome vertebrates 1182:1204 gnathostome vertebrates 1182:1204 Phylogenetic analyses of the deduced proteins confirm their homology and relationships with the respective gonadotropin subunit proteins of gnathostome vertebrates. 26205349 9 99 theme quiescent 1526:1534 arg1 phase 1536:1540 the sexually quiescent phase 1513:1540 the sexually quiescent phase 1513:1540 In the sexually quiescent phase, the transcript expression is low while in the recrudescent phase, the expressions are differential, high, and varied with regard to sex and reproductive phase. 26205349 0 100 dep cloning 10:16 arg1 phylogeny 142:150 phylogeny 142:150 phylogeny 142:150 Molecular cloning and characterization of the gonadotropin subunits GPα, FSHβ, and LHβ genes in the stinging catfish Heteropneustes fossilis: phylogeny, seasonal expression and pituitary localization. 24259486 0 0 theme novel 90:94 arg1 biomarker 102:110 a novel serum biomarker 88:110 a novel serum biomarker for hepatocellular carcinoma 88:139 Proteomic profiling of N-linked glycoproteins identifies ConA-binding procathepsin D as a novel serum biomarker for hepatocellular carcinoma. 24259486 0 0 theme novel 90:94 arg1 D 83:83 ConA-binding procathepsin D 57:83 ConA-binding procathepsin D 57:83 Proteomic profiling of N-linked glycoproteins identifies ConA-binding procathepsin D as a novel serum biomarker for hepatocellular carcinoma. 24259486 8 1 theme HCC 1517:1519 arg1 diagnosis 1504:1512 diagnosis 1504:1512 diagnosis of HCC 1504:1519 This is the first report that serum ConA-pCD is increased significantly in HCC and is potentially useful as a serological biomarker for diagnosis of HCC. 24259486 1 2 theme study 158:162 arg1 aim 146:148 The aim 142:148 The aim of this study 142:162 The aim of this study was to identify novel biomarkers for the diagnosis of, and potential therapeutic targets for, hepatocellular carcinoma (HCC). 24259486 6 3 theme several 1154:1160 arg1 pI 1200:1201 pI 4.5-5.5 1200:1209 pI 4.5-5.5 1200:1209 In the serum of HCC patients, "ConA-binding proCD" (ConA-pCD) is significantly increased in concentration and this increase is comprised of several distinct upregulated acidic isoforms (pI 4.5-5.5). 24259486 6 3 theme several 1154:1160 arg1 isoforms 1190:1197 several distinct upregulated acidic isoforms 1154:1197 several distinct upregulated acidic isoforms (pI 4.5-5.5) 1154:1210 In the serum of HCC patients, "ConA-binding proCD" (ConA-pCD) is significantly increased in concentration and this increase is comprised of several distinct upregulated acidic isoforms (pI 4.5-5.5). 24259486 6 4 theme HCC 1030:1032 arg1 patients 1034:1041 HCC patients 1030:1041 HCC patients 1030:1041 In the serum of HCC patients, "ConA-binding proCD" (ConA-pCD) is significantly increased in concentration and this increase is comprised of several distinct upregulated acidic isoforms (pI 4.5-5.5). 24259486 0 5 link N-linked 23:30 arg1 glycoproteins 32:44 N-linked glycoproteins 23:44 N-linked glycoproteins 23:44 Proteomic profiling of N-linked glycoproteins identifies ConA-binding procathepsin D as a novel serum biomarker for hepatocellular carcinoma. 24259486 2 6 theme N-linked 345:352 arg1 glycoproteins 354:366 N-linked glycoproteins 345:366 N-linked glycoproteins from nontumorous liver and HCC tissues followed by 2DE and protein identification by MS. Twenty-eight differentially expressed proteins were identified 345:518 Multilectin affinity chromatography was used to enrich N-linked glycoproteins from nontumorous liver and HCC tissues followed by 2DE and protein identification by MS. Twenty-eight differentially expressed proteins were identified. 24259486 5 7 gly glycoforms 971:980 arg1 CD 995:996 CD 995:996 CD 995:996 Prefractionation using individual lectins demonstrated an elevation in ConA-binding glycoforms of proCD and CD in HCC tissues. 24259486 5 7 gly glycoforms 971:980 arg1 proCD 985:989 proCD 985:989 proCD 985:989 Prefractionation using individual lectins demonstrated an elevation in ConA-binding glycoforms of proCD and CD in HCC tissues. 24259486 8 8 theme serum 1398:1402 arg1 ConA-pCD 1404:1411 serum ConA-pCD 1398:1411 serum ConA-pCD 1398:1411 This is the first report that serum ConA-pCD is increased significantly in HCC and is potentially useful as a serological biomarker for diagnosis of HCC. 24259486 3 9 theme human 585:589 arg1 carboxylesterase 597:612 human liver carboxylesterase 1 585:614 human liver carboxylesterase 1 585:614 Western blotting validated consistently lower concentrations of human liver carboxylesterase 1 and haptoglobin, and higher concentration of procathepsin D (pCD) in HCC tissues. 24259486 5 10 theme proCD 985:989 arg1 glycoforms 971:980 ConA-binding glycoforms 958:980 ConA-binding glycoforms of proCD and CD in HCC tissues 958:1011 Prefractionation using individual lectins demonstrated an elevation in ConA-binding glycoforms of proCD and CD in HCC tissues. 24259486 0 11 theme serum 96:100 arg1 biomarker 102:110 a novel serum biomarker 88:110 a novel serum biomarker for hepatocellular carcinoma 88:139 Proteomic profiling of N-linked glycoproteins identifies ConA-binding procathepsin D as a novel serum biomarker for hepatocellular carcinoma. 24259486 0 11 theme serum 96:100 arg1 D 83:83 ConA-binding procathepsin D 57:83 ConA-binding procathepsin D 57:83 Proteomic profiling of N-linked glycoproteins identifies ConA-binding procathepsin D as a novel serum biomarker for hepatocellular carcinoma. 24259486 4 12 theme CD 883:884 arg1 high-levels 868:878 high-levels 868:878 high-levels of CD 868:884 Knockdown of cathepsin D (CD) expression mediated by siRNA significantly inhibited the in vitro invasion of two HCC cell lines, SNU449 and SNU473, which normally secrete high-levels of CD. 24259486 3 13 theme liver 591:595 arg1 carboxylesterase 597:612 human liver carboxylesterase 1 585:614 human liver carboxylesterase 1 585:614 Western blotting validated consistently lower concentrations of human liver carboxylesterase 1 and haptoglobin, and higher concentration of procathepsin D (pCD) in HCC tissues. 24259486 1 14 theme hepatocellular 258:271 arg1 HCC 284:286 HCC 284:286 HCC 284:286 The aim of this study was to identify novel biomarkers for the diagnosis of, and potential therapeutic targets for, hepatocellular carcinoma (HCC). 24259486 1 14 theme hepatocellular 258:271 arg1 carcinoma 273:281 hepatocellular carcinoma 258:281 hepatocellular carcinoma (HCC) 258:287 The aim of this study was to identify novel biomarkers for the diagnosis of, and potential therapeutic targets for, hepatocellular carcinoma (HCC). 24259486 0 15 theme hepatocellular 116:129 arg1 carcinoma 131:139 hepatocellular carcinoma 116:139 hepatocellular carcinoma 116:139 Proteomic profiling of N-linked glycoproteins identifies ConA-binding procathepsin D as a novel serum biomarker for hepatocellular carcinoma. 24259486 2 16 link N-linked 345:352 arg1 glycoproteins 354:366 N-linked glycoproteins 345:366 N-linked glycoproteins from nontumorous liver and HCC tissues followed by 2DE and protein identification by MS. Twenty-eight differentially expressed proteins were identified 345:518 Multilectin affinity chromatography was used to enrich N-linked glycoproteins from nontumorous liver and HCC tissues followed by 2DE and protein identification by MS. Twenty-eight differentially expressed proteins were identified. 24259486 6 17 theme ConA-binding 1045:1056 arg1 ConA-pCD 1066:1073 ConA-pCD 1066:1073 ConA-pCD 1066:1073 In the serum of HCC patients, "ConA-binding proCD" (ConA-pCD) is significantly increased in concentration and this increase is comprised of several distinct upregulated acidic isoforms (pI 4.5-5.5). 24259486 6 17 theme ConA-binding 1045:1056 arg1 " 1063:1063 "ConA-binding proCD" 1044:1063 "ConA-binding proCD" (ConA-pCD) 1044:1074 In the serum of HCC patients, "ConA-binding proCD" (ConA-pCD) is significantly increased in concentration and this increase is comprised of several distinct upregulated acidic isoforms (pI 4.5-5.5). 24259486 6 18 theme upregulated 1171:1181 arg1 pI 1200:1201 pI 4.5-5.5 1200:1209 pI 4.5-5.5 1200:1209 In the serum of HCC patients, "ConA-binding proCD" (ConA-pCD) is significantly increased in concentration and this increase is comprised of several distinct upregulated acidic isoforms (pI 4.5-5.5). 24259486 6 18 theme upregulated 1171:1181 arg1 isoforms 1190:1197 several distinct upregulated acidic isoforms 1154:1197 several distinct upregulated acidic isoforms (pI 4.5-5.5) 1154:1210 In the serum of HCC patients, "ConA-binding proCD" (ConA-pCD) is significantly increased in concentration and this increase is comprised of several distinct upregulated acidic isoforms (pI 4.5-5.5). 24259486 2 19 theme Twenty-eight 457:468 arg1 proteins 495:502 Twenty-eight differentially expressed proteins 457:502 Twenty-eight differentially expressed proteins 457:502 Multilectin affinity chromatography was used to enrich N-linked glycoproteins from nontumorous liver and HCC tissues followed by 2DE and protein identification by MS. Twenty-eight differentially expressed proteins were identified. 24259486 6 20 dep patients 1034:1041 arg1 the 1017:1019 the 1017:1019 the 1017:1019 In the serum of HCC patients, "ConA-binding proCD" (ConA-pCD) is significantly increased in concentration and this increase is comprised of several distinct upregulated acidic isoforms (pI 4.5-5.5). 24259486 6 20 dep patients 1034:1041 arg1 serum 1021:1025 serum 1021:1025 serum 1021:1025 In the serum of HCC patients, "ConA-binding proCD" (ConA-pCD) is significantly increased in concentration and this increase is comprised of several distinct upregulated acidic isoforms (pI 4.5-5.5). 24259486 5 21 from elevation 945:953 arg1 glycoforms 971:980 ConA-binding glycoforms 958:980 ConA-binding glycoforms of proCD and CD in HCC tissues 958:1011 Prefractionation using individual lectins demonstrated an elevation in ConA-binding glycoforms of proCD and CD in HCC tissues. 24259486 5 22 theme HCC 1001:1003 arg1 tissues 1005:1011 HCC tissues 1001:1011 HCC tissues 1001:1011 Prefractionation using individual lectins demonstrated an elevation in ConA-binding glycoforms of proCD and CD in HCC tissues. 24259486 5 23 from tissues 1005:1011 arg1 glycoforms 971:980 ConA-binding glycoforms 958:980 ConA-binding glycoforms of proCD and CD in HCC tissues 958:1011 Prefractionation using individual lectins demonstrated an elevation in ConA-binding glycoforms of proCD and CD in HCC tissues. 24259486 2 24 theme HCC 395:397 arg1 tissues 399:405 HCC tissues 395:405 HCC tissues 395:405 Multilectin affinity chromatography was used to enrich N-linked glycoproteins from nontumorous liver and HCC tissues followed by 2DE and protein identification by MS. Twenty-eight differentially expressed proteins were identified. 24259486 2 25 theme expressed 485:493 arg1 proteins 495:502 Twenty-eight differentially expressed proteins 457:502 Twenty-eight differentially expressed proteins 457:502 Multilectin affinity chromatography was used to enrich N-linked glycoproteins from nontumorous liver and HCC tissues followed by 2DE and protein identification by MS. Twenty-eight differentially expressed proteins were identified. 24259486 5 26 from proCD 985:989 arg1 tissues 1005:1011 HCC tissues 1001:1011 HCC tissues 1001:1011 Prefractionation using individual lectins demonstrated an elevation in ConA-binding glycoforms of proCD and CD in HCC tissues. 24259486 7 27 theme HCC 1322:1324 arg1 diagnosis 1326:1334 HCC diagnosis 1322:1334 HCC diagnosis 1322:1334 Receiver operating characteristic analysis showed that the sensitivity and specificity of serum ConA-pCD for HCC diagnosis were 85% and 80%, respectively. 24259486 2 28 used used 330:333 arg2 chromatography 311:324 Multilectin affinity chromatography 290:324 Multilectin affinity chromatography 290:324 Multilectin affinity chromatography was used to enrich N-linked glycoproteins from nontumorous liver and HCC tissues followed by 2DE and protein identification by MS. Twenty-eight differentially expressed proteins were identified. 24259486 5 29 theme ConA-binding 958:969 arg1 glycoforms 971:980 ConA-binding glycoforms 958:980 ConA-binding glycoforms of proCD and CD in HCC tissues 958:1011 Prefractionation using individual lectins demonstrated an elevation in ConA-binding glycoforms of proCD and CD in HCC tissues. 24259486 1 30 theme novel 180:184 arg1 biomarkers 186:195 novel biomarkers 180:195 novel biomarkers for the diagnosis of 180:216 The aim of this study was to identify novel biomarkers for the diagnosis of, and potential therapeutic targets for, hepatocellular carcinoma (HCC). 24259486 0 31 theme Proteomic 0:8 arg1 profiling 10:18 Proteomic profiling 0:18 Proteomic profiling of N-linked glycoproteins 0:44 Proteomic profiling of N-linked glycoproteins identifies ConA-binding procathepsin D as a novel serum biomarker for hepatocellular carcinoma. 24259486 2 32 theme affinity 302:309 arg1 chromatography 311:324 Multilectin affinity chromatography 290:324 Multilectin affinity chromatography 290:324 Multilectin affinity chromatography was used to enrich N-linked glycoproteins from nontumorous liver and HCC tissues followed by 2DE and protein identification by MS. Twenty-eight differentially expressed proteins were identified. 24259486 0 33 theme N-linked 23:30 arg1 glycoproteins 32:44 N-linked glycoproteins 23:44 N-linked glycoproteins 23:44 Proteomic profiling of N-linked glycoproteins identifies ConA-binding procathepsin D as a novel serum biomarker for hepatocellular carcinoma. 24259486 5 34 theme individual 910:919 arg1 lectins 921:927 individual lectins 910:927 individual lectins 910:927 Prefractionation using individual lectins demonstrated an elevation in ConA-binding glycoforms of proCD and CD in HCC tissues. 24259486 2 35 theme Multilectin 290:300 arg1 chromatography 311:324 Multilectin affinity chromatography 290:324 Multilectin affinity chromatography 290:324 Multilectin affinity chromatography was used to enrich N-linked glycoproteins from nontumorous liver and HCC tissues followed by 2DE and protein identification by MS. Twenty-eight differentially expressed proteins were identified. 24259486 8 36 theme first 1380:1384 arg1 report 1386:1391 the first report 1376:1391 the first report that serum ConA-pCD is increased significantly in HCC and is potentially useful as a serological biomarker for diagnosis of HCC 1376:1519 This is the first report that serum ConA-pCD is increased significantly in HCC and is potentially useful as a serological biomarker for diagnosis of HCC. 24259486 8 36 theme first 1380:1384 arg1 This 1368:1371 This 1368:1371 This 1368:1371 This is the first report that serum ConA-pCD is increased significantly in HCC and is potentially useful as a serological biomarker for diagnosis of HCC. 24259486 6 37 theme proCD 1058:1062 arg1 ConA-pCD 1066:1073 ConA-pCD 1066:1073 ConA-pCD 1066:1073 In the serum of HCC patients, "ConA-binding proCD" (ConA-pCD) is significantly increased in concentration and this increase is comprised of several distinct upregulated acidic isoforms (pI 4.5-5.5). 24259486 6 37 theme proCD 1058:1062 arg1 " 1063:1063 "ConA-binding proCD" 1044:1063 "ConA-binding proCD" (ConA-pCD) 1044:1074 In the serum of HCC patients, "ConA-binding proCD" (ConA-pCD) is significantly increased in concentration and this increase is comprised of several distinct upregulated acidic isoforms (pI 4.5-5.5). 24259486 2 38 theme protein 427:433 arg1 identification 435:448 protein identification 427:448 protein identification 427:448 Multilectin affinity chromatography was used to enrich N-linked glycoproteins from nontumorous liver and HCC tissues followed by 2DE and protein identification by MS. Twenty-eight differentially expressed proteins were identified. 24259486 1 39 dep potential 223:231 arg1 therapeutic 233:243 therapeutic 233:243 therapeutic 233:243 The aim of this study was to identify novel biomarkers for the diagnosis of, and potential therapeutic targets for, hepatocellular carcinoma (HCC). 24259486 4 40 dep in 785:786 arg1 vitro 788:792 vitro 788:792 vitro 788:792 Knockdown of cathepsin D (CD) expression mediated by siRNA significantly inhibited the in vitro invasion of two HCC cell lines, SNU449 and SNU473, which normally secrete high-levels of CD. 24259486 4 41 theme D 721:721 arg1 expression 728:737 cathepsin D (CD) expression 711:737 cathepsin D (CD) expression mediated by siRNA 711:755 Knockdown of cathepsin D (CD) expression mediated by siRNA significantly inhibited the in vitro invasion of two HCC cell lines, SNU449 and SNU473, which normally secrete high-levels of CD. 24259486 4 42 dep inhibited 771:779 arg1 secrete 860:866 secrete 860:866 secrete high-levels of CD 860:884 Knockdown of cathepsin D (CD) expression mediated by siRNA significantly inhibited the in vitro invasion of two HCC cell lines, SNU449 and SNU473, which normally secrete high-levels of CD. 24259486 3 43 theme HCC 685:687 arg1 tissues 689:695 HCC tissues 685:695 HCC tissues 685:695 Western blotting validated consistently lower concentrations of human liver carboxylesterase 1 and haptoglobin, and higher concentration of procathepsin D (pCD) in HCC tissues. 24259486 3 44 theme higher 637:642 arg1 concentration 644:656 higher concentration 637:656 higher concentration of procathepsin D (pCD) 637:680 Western blotting validated consistently lower concentrations of human liver carboxylesterase 1 and haptoglobin, and higher concentration of procathepsin D (pCD) in HCC tissues. 24259486 7 45 theme serum 1303:1307 arg1 ConA-pCD 1309:1316 serum ConA-pCD 1303:1316 serum ConA-pCD 1303:1316 Receiver operating characteristic analysis showed that the sensitivity and specificity of serum ConA-pCD for HCC diagnosis were 85% and 80%, respectively. 24259486 0 46 theme glycoproteins 32:44 arg1 profiling 10:18 Proteomic profiling 0:18 Proteomic profiling of N-linked glycoproteins 0:44 Proteomic profiling of N-linked glycoproteins identifies ConA-binding procathepsin D as a novel serum biomarker for hepatocellular carcinoma. 24259486 2 47 gly glycoproteins 354:366 arg1 glycoproteins 354:366 N-linked glycoproteins 345:366 N-linked glycoproteins from nontumorous liver and HCC tissues followed by 2DE and protein identification by MS. Twenty-eight differentially expressed proteins were identified 345:518 Multilectin affinity chromatography was used to enrich N-linked glycoproteins from nontumorous liver and HCC tissues followed by 2DE and protein identification by MS. Twenty-eight differentially expressed proteins were identified. 24259486 4 48 theme in 785:786 arg1 invasion 794:801 the in vitro invasion 781:801 the in vitro invasion of two HCC cell lines, SNU449 and SNU473 781:842 Knockdown of cathepsin D (CD) expression mediated by siRNA significantly inhibited the in vitro invasion of two HCC cell lines, SNU449 and SNU473, which normally secrete high-levels of CD. 24259486 7 49 theme ConA-pCD 1309:1316 arg1 specificity 1288:1298 specificity 1288:1298 specificity 1288:1298 Receiver operating characteristic analysis showed that the sensitivity and specificity of serum ConA-pCD for HCC diagnosis were 85% and 80%, respectively. 24259486 7 49 theme ConA-pCD 1309:1316 arg1 sensitivity 1272:1282 sensitivity 1272:1282 sensitivity 1272:1282 Receiver operating characteristic analysis showed that the sensitivity and specificity of serum ConA-pCD for HCC diagnosis were 85% and 80%, respectively. 24259486 0 50 theme procathepsin 70:81 arg1 biomarker 102:110 a novel serum biomarker 88:110 a novel serum biomarker for hepatocellular carcinoma 88:139 Proteomic profiling of N-linked glycoproteins identifies ConA-binding procathepsin D as a novel serum biomarker for hepatocellular carcinoma. 24259486 0 50 theme procathepsin 70:81 arg1 D 83:83 ConA-binding procathepsin D 57:83 ConA-binding procathepsin D 57:83 Proteomic profiling of N-linked glycoproteins identifies ConA-binding procathepsin D as a novel serum biomarker for hepatocellular carcinoma. 24259486 8 51 dep report 1386:1391 arg1 useful 1466:1471 useful 1466:1471 useful 1466:1471 This is the first report that serum ConA-pCD is increased significantly in HCC and is potentially useful as a serological biomarker for diagnosis of HCC. 24259486 8 51 dep report 1386:1391 arg1 increased 1416:1424 increased 1416:1424 is increased significantly in HCC 1413:1445 This is the first report that serum ConA-pCD is increased significantly in HCC and is potentially useful as a serological biomarker for diagnosis of HCC. 24259486 5 52 theme CD 995:996 arg1 glycoforms 971:980 ConA-binding glycoforms 958:980 ConA-binding glycoforms of proCD and CD in HCC tissues 958:1011 Prefractionation using individual lectins demonstrated an elevation in ConA-binding glycoforms of proCD and CD in HCC tissues. 24259486 2 53 from liver 385:389 arg1 glycoproteins 354:366 N-linked glycoproteins 345:366 N-linked glycoproteins from nontumorous liver and HCC tissues followed by 2DE and protein identification by MS. Twenty-eight differentially expressed proteins were identified 345:518 Multilectin affinity chromatography was used to enrich N-linked glycoproteins from nontumorous liver and HCC tissues followed by 2DE and protein identification by MS. Twenty-eight differentially expressed proteins were identified. 24259486 4 54 theme expression 728:737 arg1 Knockdown 698:706 Knockdown 698:706 Knockdown of cathepsin D (CD) expression mediated by siRNA 698:755 Knockdown of cathepsin D (CD) expression mediated by siRNA significantly inhibited the in vitro invasion of two HCC cell lines, SNU449 and SNU473, which normally secrete high-levels of CD. 24259486 0 55 theme ConA-binding 57:68 arg1 biomarker 102:110 a novel serum biomarker 88:110 a novel serum biomarker for hepatocellular carcinoma 88:139 Proteomic profiling of N-linked glycoproteins identifies ConA-binding procathepsin D as a novel serum biomarker for hepatocellular carcinoma. 24259486 0 55 theme ConA-binding 57:68 arg1 D 83:83 ConA-binding procathepsin D 57:83 ConA-binding procathepsin D 57:83 Proteomic profiling of N-linked glycoproteins identifies ConA-binding procathepsin D as a novel serum biomarker for hepatocellular carcinoma. 24259486 6 56 theme acidic 1183:1188 arg1 pI 1200:1201 pI 4.5-5.5 1200:1209 pI 4.5-5.5 1200:1209 In the serum of HCC patients, "ConA-binding proCD" (ConA-pCD) is significantly increased in concentration and this increase is comprised of several distinct upregulated acidic isoforms (pI 4.5-5.5). 24259486 6 56 theme acidic 1183:1188 arg1 isoforms 1190:1197 several distinct upregulated acidic isoforms 1154:1197 several distinct upregulated acidic isoforms (pI 4.5-5.5) 1154:1210 In the serum of HCC patients, "ConA-binding proCD" (ConA-pCD) is significantly increased in concentration and this increase is comprised of several distinct upregulated acidic isoforms (pI 4.5-5.5). 24259486 2 57 from tissues 399:405 arg1 glycoproteins 354:366 N-linked glycoproteins 345:366 N-linked glycoproteins from nontumorous liver and HCC tissues followed by 2DE and protein identification by MS. Twenty-eight differentially expressed proteins were identified 345:518 Multilectin affinity chromatography was used to enrich N-linked glycoproteins from nontumorous liver and HCC tissues followed by 2DE and protein identification by MS. Twenty-eight differentially expressed proteins were identified. 24259486 3 58 theme Western 521:527 arg1 blotting 529:536 Western blotting 521:536 Western blotting 521:536 Western blotting validated consistently lower concentrations of human liver carboxylesterase 1 and haptoglobin, and higher concentration of procathepsin D (pCD) in HCC tissues. 24259486 4 59 theme cell 814:817 arg1 SNU449 826:831 SNU449 826:831 SNU449 826:831 Knockdown of cathepsin D (CD) expression mediated by siRNA significantly inhibited the in vitro invasion of two HCC cell lines, SNU449 and SNU473, which normally secrete high-levels of CD. 24259486 4 59 theme cell 814:817 arg1 lines 819:823 two HCC cell lines 806:823 two HCC cell lines 806:823 Knockdown of cathepsin D (CD) expression mediated by siRNA significantly inhibited the in vitro invasion of two HCC cell lines, SNU449 and SNU473, which normally secrete high-levels of CD. 24259486 4 59 theme cell 814:817 arg1 SNU473 837:842 SNU473 837:842 SNU473 837:842 Knockdown of cathepsin D (CD) expression mediated by siRNA significantly inhibited the in vitro invasion of two HCC cell lines, SNU449 and SNU473, which normally secrete high-levels of CD. 24259486 3 60 theme D 674:674 arg1 concentrations 567:580 consistently lower concentrations 548:580 consistently lower concentrations of human liver carboxylesterase 1 and haptoglobin 548:630 Western blotting validated consistently lower concentrations of human liver carboxylesterase 1 and haptoglobin, and higher concentration of procathepsin D (pCD) in HCC tissues. 24259486 3 60 theme D 674:674 arg1 concentration 644:656 higher concentration 637:656 higher concentration of procathepsin D (pCD) 637:680 Western blotting validated consistently lower concentrations of human liver carboxylesterase 1 and haptoglobin, and higher concentration of procathepsin D (pCD) in HCC tissues. 24259486 0 61 gly glycoproteins 32:44 arg1 glycoproteins 32:44 N-linked glycoproteins 23:44 N-linked glycoproteins 23:44 Proteomic profiling of N-linked glycoproteins identifies ConA-binding procathepsin D as a novel serum biomarker for hepatocellular carcinoma. 24259486 4 62 theme cathepsin 711:719 arg1 CD 724:725 CD 724:725 CD 724:725 Knockdown of cathepsin D (CD) expression mediated by siRNA significantly inhibited the in vitro invasion of two HCC cell lines, SNU449 and SNU473, which normally secrete high-levels of CD. 24259486 4 62 theme cathepsin 711:719 arg1 D 721:721 cathepsin D 711:721 cathepsin D (CD) expression mediated by siRNA 711:755 Knockdown of cathepsin D (CD) expression mediated by siRNA significantly inhibited the in vitro invasion of two HCC cell lines, SNU449 and SNU473, which normally secrete high-levels of CD. 24259486 3 63 theme carboxylesterase 597:612 arg1 concentrations 567:580 consistently lower concentrations 548:580 consistently lower concentrations of human liver carboxylesterase 1 and haptoglobin 548:630 Western blotting validated consistently lower concentrations of human liver carboxylesterase 1 and haptoglobin, and higher concentration of procathepsin D (pCD) in HCC tissues. 24259486 3 63 theme carboxylesterase 597:612 arg1 concentration 644:656 higher concentration 637:656 higher concentration of procathepsin D (pCD) 637:680 Western blotting validated consistently lower concentrations of human liver carboxylesterase 1 and haptoglobin, and higher concentration of procathepsin D (pCD) in HCC tissues. 24259486 6 64 theme distinct 1162:1169 arg1 pI 1200:1201 pI 4.5-5.5 1200:1209 pI 4.5-5.5 1200:1209 In the serum of HCC patients, "ConA-binding proCD" (ConA-pCD) is significantly increased in concentration and this increase is comprised of several distinct upregulated acidic isoforms (pI 4.5-5.5). 24259486 6 64 theme distinct 1162:1169 arg1 isoforms 1190:1197 several distinct upregulated acidic isoforms 1154:1197 several distinct upregulated acidic isoforms (pI 4.5-5.5) 1154:1210 In the serum of HCC patients, "ConA-binding proCD" (ConA-pCD) is significantly increased in concentration and this increase is comprised of several distinct upregulated acidic isoforms (pI 4.5-5.5). 24259486 7 65 dep sensitivity 1272:1282 arg1 the 1268:1270 the 1268:1270 the 1268:1270 Receiver operating characteristic analysis showed that the sensitivity and specificity of serum ConA-pCD for HCC diagnosis were 85% and 80%, respectively. 24259486 3 66 theme lower 561:565 arg1 concentrations 567:580 consistently lower concentrations 548:580 consistently lower concentrations of human liver carboxylesterase 1 and haptoglobin 548:630 Western blotting validated consistently lower concentrations of human liver carboxylesterase 1 and haptoglobin, and higher concentration of procathepsin D (pCD) in HCC tissues. 24259486 4 67 theme HCC 810:812 arg1 SNU449 826:831 SNU449 826:831 SNU449 826:831 Knockdown of cathepsin D (CD) expression mediated by siRNA significantly inhibited the in vitro invasion of two HCC cell lines, SNU449 and SNU473, which normally secrete high-levels of CD. 24259486 4 67 theme HCC 810:812 arg1 lines 819:823 two HCC cell lines 806:823 two HCC cell lines 806:823 Knockdown of cathepsin D (CD) expression mediated by siRNA significantly inhibited the in vitro invasion of two HCC cell lines, SNU449 and SNU473, which normally secrete high-levels of CD. 24259486 4 67 theme HCC 810:812 arg1 SNU473 837:842 SNU473 837:842 SNU473 837:842 Knockdown of cathepsin D (CD) expression mediated by siRNA significantly inhibited the in vitro invasion of two HCC cell lines, SNU449 and SNU473, which normally secrete high-levels of CD. 24259486 5 68 from CD 995:996 arg1 tissues 1005:1011 HCC tissues 1001:1011 HCC tissues 1001:1011 Prefractionation using individual lectins demonstrated an elevation in ConA-binding glycoforms of proCD and CD in HCC tissues. 24259486 4 69 theme lines 819:823 arg1 invasion 794:801 the in vitro invasion 781:801 the in vitro invasion of two HCC cell lines, SNU449 and SNU473 781:842 Knockdown of cathepsin D (CD) expression mediated by siRNA significantly inhibited the in vitro invasion of two HCC cell lines, SNU449 and SNU473, which normally secrete high-levels of CD. 24259486 2 70 theme nontumorous 373:383 arg1 liver 385:389 nontumorous liver 373:389 nontumorous liver 373:389 Multilectin affinity chromatography was used to enrich N-linked glycoproteins from nontumorous liver and HCC tissues followed by 2DE and protein identification by MS. Twenty-eight differentially expressed proteins were identified. 24259486 5 71 from glycoforms 971:980 arg1 tissues 1005:1011 HCC tissues 1001:1011 HCC tissues 1001:1011 Prefractionation using individual lectins demonstrated an elevation in ConA-binding glycoforms of proCD and CD in HCC tissues. 24259486 1 72 theme potential 223:231 arg1 targets 245:251 potential therapeutic targets 223:251 potential therapeutic targets for, hepatocellular carcinoma (HCC) 223:287 The aim of this study was to identify novel biomarkers for the diagnosis of, and potential therapeutic targets for, hepatocellular carcinoma (HCC). 24259486 7 73 theme characteristic 1232:1245 arg1 analysis 1247:1254 characteristic analysis 1232:1254 characteristic analysis 1232:1254 Receiver operating characteristic analysis showed that the sensitivity and specificity of serum ConA-pCD for HCC diagnosis were 85% and 80%, respectively. 24259486 8 74 theme serological 1478:1488 arg1 biomarker 1490:1498 a serological biomarker 1476:1498 a serological biomarker for diagnosis of HCC 1476:1519 This is the first report that serum ConA-pCD is increased significantly in HCC and is potentially useful as a serological biomarker for diagnosis of HCC. 24259486 3 75 theme procathepsin 661:672 arg1 pCD 677:679 pCD 677:679 pCD 677:679 Western blotting validated consistently lower concentrations of human liver carboxylesterase 1 and haptoglobin, and higher concentration of procathepsin D (pCD) in HCC tissues. 24259486 3 75 theme procathepsin 661:672 arg1 D 674:674 procathepsin D 661:674 procathepsin D (pCD) 661:680 Western blotting validated consistently lower concentrations of human liver carboxylesterase 1 and haptoglobin, and higher concentration of procathepsin D (pCD) in HCC tissues. 24259486 3 76 theme haptoglobin 620:630 arg1 concentrations 567:580 consistently lower concentrations 548:580 consistently lower concentrations of human liver carboxylesterase 1 and haptoglobin 548:630 Western blotting validated consistently lower concentrations of human liver carboxylesterase 1 and haptoglobin, and higher concentration of procathepsin D (pCD) in HCC tissues. 24259486 3 76 theme haptoglobin 620:630 arg1 concentration 644:656 higher concentration 637:656 higher concentration of procathepsin D (pCD) 637:680 Western blotting validated consistently lower concentrations of human liver carboxylesterase 1 and haptoglobin, and higher concentration of procathepsin D (pCD) in HCC tissues. 28373131 0 0 theme non-covalent 87:98 arg1 interactions 113:124 non-covalent and covalent interactions 87:124 non-covalent and covalent interactions 87:124 Cartilage oligomeric matrix protein forms protein complexes with synovial lubricin via non-covalent and covalent interactions. 28373131 7 1 theme COMP 1131:1134 arg1 C-terminal 1090:1099 C-terminal 1090:1099 C-terminal 1090:1099 RC fragment solid-phase binding assays showed that the C-terminal (amino acids (AA) 518-757) of COMP bound non-covalently to the N-terminal of lubricin (AA 105-202). 28373131 7 1 theme COMP 1131:1134 arg1 acids 1108:1112 amino acids 1102:1112 amino acids (AA) 518-757 1102:1125 RC fragment solid-phase binding assays showed that the C-terminal (amino acids (AA) 518-757) of COMP bound non-covalently to the N-terminal of lubricin (AA 105-202). 28373131 4 2 used used 619:622 arg2 SF 587:588 SF 587:588 SF 587:588 DESIGN Synovial fluid (SF) from arthritic patients was used to detect possible COMP-lubricin complexes by immunological methods. 28373131 4 2 used used 619:622 arg2 fluid 580:584 DESIGN Synovial fluid 564:584 DESIGN Synovial fluid (SF) from arthritic patients 564:613 DESIGN Synovial fluid (SF) from arthritic patients was used to detect possible COMP-lubricin complexes by immunological methods. 28373131 6 3 theme RESULTS 895:901 arg1 complexes 917:925 RESULTS COMP-lubricin complexes 895:925 RESULTS COMP-lubricin complexes 895:925 RESULTS COMP-lubricin complexes were identified in the SF of arthritic patients by Western blot, co-immunoprecipitation and sandwich ELISA. 28373131 11 4 theme arthritis 1777:1785 arg1 arthritis 1843:1851 rheumatoid arthritis 1832:1851 rheumatoid arthritis (RA) 1832:1856 This complex between lubricin and the cartilage protein COMP can be identified in the SF of patients with arthritis conditions including osteoarthritis (OA) and rheumatoid arthritis (RA). 28373131 11 4 theme arthritis 1777:1785 arg1 osteoarthritis 1808:1821 osteoarthritis 1808:1821 osteoarthritis (OA) 1808:1826 This complex between lubricin and the cartilage protein COMP can be identified in the SF of patients with arthritis conditions including osteoarthritis (OA) and rheumatoid arthritis (RA). 28373131 11 4 theme arthritis 1777:1785 arg1 conditions 1787:1796 arthritis conditions 1777:1796 arthritis conditions including osteoarthritis (OA) and rheumatoid arthritis (RA) 1777:1856 This complex between lubricin and the cartilage protein COMP can be identified in the SF of patients with arthritis conditions including osteoarthritis (OA) and rheumatoid arthritis (RA). 28373131 2 5 with interaction 402:412 arg1 COMP 456:459 COMP 456:459 COMP 456:459 Given that adherence of the lubricating protein, lubricin, to the cartilage surface is critical for boundary lubrication, an interaction with cartilage oligomeric matrix protein (COMP) was investigated. 28373131 2 5 with interaction 402:412 arg1 protein 447:453 cartilage oligomeric matrix protein 419:453 cartilage oligomeric matrix protein (COMP) 419:460 Given that adherence of the lubricating protein, lubricin, to the cartilage surface is critical for boundary lubrication, an interaction with cartilage oligomeric matrix protein (COMP) was investigated. 28373131 8 6 from cysteines 1314:1322 arg1 lubricin 1327:1334 lubricin 1327:1334 lubricin 1327:1334 Mass spectrometry determined that although cysteines throughout COMP were involved in binding with lubricin, the cysteines in lubricin were primarily focused to an N-terminal region (AA 64-86). 28373131 9 7 theme two-step 1487:1494 arg1 mechanism 1496:1504 a two-step mechanism 1485:1504 a two-step mechanism to strongly bind lubricin to COMP 1485:1538 The close proximity of the non-covalent and disulfide binding domains on lubricin suggest a two-step mechanism to strongly bind lubricin to COMP. 28373131 4 8 theme Synovial 571:578 arg1 SF 587:588 SF 587:588 SF 587:588 DESIGN Synovial fluid (SF) from arthritic patients was used to detect possible COMP-lubricin complexes by immunological methods. 28373131 4 8 theme Synovial 571:578 arg1 fluid 580:584 DESIGN Synovial fluid 564:584 DESIGN Synovial fluid (SF) from arthritic patients 564:613 DESIGN Synovial fluid (SF) from arthritic patients was used to detect possible COMP-lubricin complexes by immunological methods. 28373131 0 9 theme covalent 104:111 arg1 interactions 113:124 non-covalent and covalent interactions 87:124 non-covalent and covalent interactions 87:124 Cartilage oligomeric matrix protein forms protein complexes with synovial lubricin via non-covalent and covalent interactions. 28373131 11 10 theme patients 1763:1770 arg1 SF 1757:1758 the SF 1753:1758 the SF of patients with arthritis conditions including osteoarthritis (OA) and rheumatoid arthritis (RA) 1753:1856 This complex between lubricin and the cartilage protein COMP can be identified in the SF of patients with arthritis conditions including osteoarthritis (OA) and rheumatoid arthritis (RA). 28373131 2 11 theme lubricating 305:315 arg1 lubricin 326:333 lubricin 326:333 lubricin 326:333 Given that adherence of the lubricating protein, lubricin, to the cartilage surface is critical for boundary lubrication, an interaction with cartilage oligomeric matrix protein (COMP) was investigated. 28373131 2 11 theme lubricating 305:315 arg1 protein 317:323 the lubricating protein 301:323 the lubricating protein 301:323 Given that adherence of the lubricating protein, lubricin, to the cartilage surface is critical for boundary lubrication, an interaction with cartilage oligomeric matrix protein (COMP) was investigated. 28373131 6 12 theme sandwich 1019:1026 arg1 ELISA 1028:1032 sandwich ELISA 1019:1032 sandwich ELISA 1019:1032 RESULTS COMP-lubricin complexes were identified in the SF of arthritic patients by Western blot, co-immunoprecipitation and sandwich ELISA. 28373131 5 13 theme lubricin 719:726 arg1 fragments 728:736 Recombinant (RC) COMP and lubricin fragments 693:736 fragments 728:736 Recombinant (RC) COMP and lubricin fragments were expressed to characterize this bonding and mass spectrometry employed to specifically identify the cysteines involved in inter-protein disulfide bonds. 28373131 9 14 theme non-covalent 1422:1433 arg1 proximity 1405:1413 The close proximity 1395:1413 The close proximity of the non-covalent and disulfide binding domains on lubricin 1395:1475 The close proximity of the non-covalent and disulfide binding domains on lubricin suggest a two-step mechanism to strongly bind lubricin to COMP. 28373131 3 15 theme abundant 489:496 arg1 protein 508:514 an abundant cartilage protein 486:514 an abundant cartilage protein 486:514 COMP, an abundant cartilage protein, is known to be important for matrix formation. 28373131 3 15 theme abundant 489:496 arg1 COMP 480:483 COMP 480:483 COMP 480:483 COMP, an abundant cartilage protein, is known to be important for matrix formation. 28373131 8 16 theme N-terminal 1365:1374 arg1 AA 1384:1385 AA 64-86 1384:1391 AA 64-86 1384:1391 Mass spectrometry determined that although cysteines throughout COMP were involved in binding with lubricin, the cysteines in lubricin were primarily focused to an N-terminal region (AA 64-86). 28373131 8 16 theme N-terminal 1365:1374 arg1 region 1376:1381 an N-terminal region 1362:1381 an N-terminal region (AA 64-86) 1362:1392 Mass spectrometry determined that although cysteines throughout COMP were involved in binding with lubricin, the cysteines in lubricin were primarily focused to an N-terminal region (AA 64-86). 28373131 10 17 theme covalent 1655:1662 arg1 bonds 1664:1668 both non-covalent and covalent bonds 1633:1668 both non-covalent and covalent bonds 1633:1668 CONCLUSION These data demonstrate that lubricin forms a complex network with COMP involving both non-covalent and covalent bonds. 28373131 4 18 theme COMP-lubricin 643:655 arg1 complexes 657:665 possible COMP-lubricin complexes 634:665 possible COMP-lubricin complexes 634:665 DESIGN Synovial fluid (SF) from arthritic patients was used to detect possible COMP-lubricin complexes by immunological methods. 28373131 6 19 theme COMP-lubricin 903:915 arg1 complexes 917:925 RESULTS COMP-lubricin complexes 895:925 RESULTS COMP-lubricin complexes 895:925 RESULTS COMP-lubricin complexes were identified in the SF of arthritic patients by Western blot, co-immunoprecipitation and sandwich ELISA. 28373131 10 20 theme non-covalent 1638:1649 arg1 bonds 1664:1668 both non-covalent and covalent bonds 1633:1668 both non-covalent and covalent bonds 1633:1668 CONCLUSION These data demonstrate that lubricin forms a complex network with COMP involving both non-covalent and covalent bonds. 28373131 9 21 from lubricin 1468:1475 arg1 proximity 1405:1413 The close proximity 1395:1413 The close proximity of the non-covalent and disulfide binding domains on lubricin 1395:1475 The close proximity of the non-covalent and disulfide binding domains on lubricin suggest a two-step mechanism to strongly bind lubricin to COMP. 28373131 1 22 dep Understanding 137:149 arg1 structure 173:181 the cartilage surface structure 151:181 the cartilage surface structure 151:181 OBJECTIVE Understanding the cartilage surface structure, lost in arthritic disease, is essential for developing strategies to effectively restore it. 28373131 1 23 theme arthritic 192:200 arg1 disease 202:208 arthritic disease 192:208 arthritic disease 192:208 OBJECTIVE Understanding the cartilage surface structure, lost in arthritic disease, is essential for developing strategies to effectively restore it. 28373131 0 24 theme oligomeric 10:19 arg1 protein 28:34 Cartilage oligomeric matrix protein 0:34 Cartilage oligomeric matrix protein 0:34 Cartilage oligomeric matrix protein forms protein complexes with synovial lubricin via non-covalent and covalent interactions. 28373131 6 25 theme Western 978:984 arg1 blot 986:989 Western blot 978:989 Western blot 978:989 RESULTS COMP-lubricin complexes were identified in the SF of arthritic patients by Western blot, co-immunoprecipitation and sandwich ELISA. 28373131 9 26 theme binding 1449:1455 arg1 domains 1457:1463 the non-covalent and disulfide binding domains 1418:1463 domains 1457:1463 The close proximity of the non-covalent and disulfide binding domains on lubricin suggest a two-step mechanism to strongly bind lubricin to COMP. 28373131 0 27 theme Cartilage 0:8 arg1 protein 28:34 Cartilage oligomeric matrix protein 0:34 Cartilage oligomeric matrix protein 0:34 Cartilage oligomeric matrix protein forms protein complexes with synovial lubricin via non-covalent and covalent interactions. 28373131 5 28 theme disulfide 878:886 arg1 bonds 888:892 inter-protein disulfide bonds 864:892 inter-protein disulfide bonds 864:892 Recombinant (RC) COMP and lubricin fragments were expressed to characterize this bonding and mass spectrometry employed to specifically identify the cysteines involved in inter-protein disulfide bonds. 28373131 9 29 theme domains 1457:1463 arg1 proximity 1405:1413 The close proximity 1395:1413 The close proximity of the non-covalent and disulfide binding domains on lubricin 1395:1475 The close proximity of the non-covalent and disulfide binding domains on lubricin suggest a two-step mechanism to strongly bind lubricin to COMP. 28373131 8 30 theme Mass 1201:1204 arg1 spectrometry 1206:1217 Mass spectrometry 1201:1217 Mass spectrometry 1201:1217 Mass spectrometry determined that although cysteines throughout COMP were involved in binding with lubricin, the cysteines in lubricin were primarily focused to an N-terminal region (AA 64-86). 28373131 7 31 theme amino 1102:1106 arg1 AA 1115:1116 AA 1115:1116 AA 1115:1116 RC fragment solid-phase binding assays showed that the C-terminal (amino acids (AA) 518-757) of COMP bound non-covalently to the N-terminal of lubricin (AA 105-202). 28373131 7 31 theme amino 1102:1106 arg1 C-terminal 1090:1099 C-terminal 1090:1099 C-terminal 1090:1099 RC fragment solid-phase binding assays showed that the C-terminal (amino acids (AA) 518-757) of COMP bound non-covalently to the N-terminal of lubricin (AA 105-202). 28373131 7 31 theme amino 1102:1106 arg1 acids 1108:1112 amino acids 1102:1112 amino acids (AA) 518-757 1102:1125 RC fragment solid-phase binding assays showed that the C-terminal (amino acids (AA) 518-757) of COMP bound non-covalently to the N-terminal of lubricin (AA 105-202). 28373131 3 32 theme matrix 546:551 arg1 formation 553:561 matrix formation 546:561 matrix formation 546:561 COMP, an abundant cartilage protein, is known to be important for matrix formation. 28373131 2 33 theme matrix 440:445 arg1 COMP 456:459 COMP 456:459 COMP 456:459 Given that adherence of the lubricating protein, lubricin, to the cartilage surface is critical for boundary lubrication, an interaction with cartilage oligomeric matrix protein (COMP) was investigated. 28373131 2 33 theme matrix 440:445 arg1 protein 447:453 cartilage oligomeric matrix protein 419:453 cartilage oligomeric matrix protein (COMP) 419:460 Given that adherence of the lubricating protein, lubricin, to the cartilage surface is critical for boundary lubrication, an interaction with cartilage oligomeric matrix protein (COMP) was investigated. 28373131 0 34 theme matrix 21:26 arg1 protein 28:34 Cartilage oligomeric matrix protein 0:34 Cartilage oligomeric matrix protein 0:34 Cartilage oligomeric matrix protein forms protein complexes with synovial lubricin via non-covalent and covalent interactions. 28373131 4 35 theme DESIGN 564:569 arg1 SF 587:588 SF 587:588 SF 587:588 DESIGN Synovial fluid (SF) from arthritic patients was used to detect possible COMP-lubricin complexes by immunological methods. 28373131 4 35 theme DESIGN 564:569 arg1 fluid 580:584 DESIGN Synovial fluid 564:584 DESIGN Synovial fluid (SF) from arthritic patients 564:613 DESIGN Synovial fluid (SF) from arthritic patients was used to detect possible COMP-lubricin complexes by immunological methods. 28373131 5 36 theme RC 706:707 arg1 COMP 710:713 Recombinant (RC) COMP and lubricin fragments 693:736 COMP 710:713 Recombinant (RC) COMP and lubricin fragments were expressed to characterize this bonding and mass spectrometry employed to specifically identify the cysteines involved in inter-protein disulfide bonds. 28373131 11 37 theme cartilage 1709:1717 arg1 COMP 1727:1730 the cartilage protein COMP 1705:1730 the cartilage protein COMP 1705:1730 This complex between lubricin and the cartilage protein COMP can be identified in the SF of patients with arthritis conditions including osteoarthritis (OA) and rheumatoid arthritis (RA). 28373131 2 38 theme protein 317:323 arg1 adherence 288:296 adherence 288:296 adherence of the lubricating protein, lubricin, to the cartilage surface 288:359 Given that adherence of the lubricating protein, lubricin, to the cartilage surface is critical for boundary lubrication, an interaction with cartilage oligomeric matrix protein (COMP) was investigated. 28373131 2 39 theme oligomeric 429:438 arg1 COMP 456:459 COMP 456:459 COMP 456:459 Given that adherence of the lubricating protein, lubricin, to the cartilage surface is critical for boundary lubrication, an interaction with cartilage oligomeric matrix protein (COMP) was investigated. 28373131 2 39 theme oligomeric 429:438 arg1 protein 447:453 cartilage oligomeric matrix protein 419:453 cartilage oligomeric matrix protein (COMP) 419:460 Given that adherence of the lubricating protein, lubricin, to the cartilage surface is critical for boundary lubrication, an interaction with cartilage oligomeric matrix protein (COMP) was investigated. 28373131 0 40 theme protein 42:48 arg1 complexes 50:58 protein complexes 42:58 protein complexes with synovial lubricin 42:81 Cartilage oligomeric matrix protein forms protein complexes with synovial lubricin via non-covalent and covalent interactions. 28373131 3 41 theme cartilage 498:506 arg1 protein 508:514 an abundant cartilage protein 486:514 an abundant cartilage protein 486:514 COMP, an abundant cartilage protein, is known to be important for matrix formation. 28373131 3 41 theme cartilage 498:506 arg1 COMP 480:483 COMP 480:483 COMP 480:483 COMP, an abundant cartilage protein, is known to be important for matrix formation. 28373131 9 42 from proximity 1405:1413 arg1 lubricin 1468:1475 lubricin 1468:1475 lubricin 1468:1475 The close proximity of the non-covalent and disulfide binding domains on lubricin suggest a two-step mechanism to strongly bind lubricin to COMP. 28373131 11 43 theme protein 1719:1725 arg1 COMP 1727:1730 the cartilage protein COMP 1705:1730 the cartilage protein COMP 1705:1730 This complex between lubricin and the cartilage protein COMP can be identified in the SF of patients with arthritis conditions including osteoarthritis (OA) and rheumatoid arthritis (RA). 28373131 2 44 theme cartilage 419:427 arg1 COMP 456:459 COMP 456:459 COMP 456:459 Given that adherence of the lubricating protein, lubricin, to the cartilage surface is critical for boundary lubrication, an interaction with cartilage oligomeric matrix protein (COMP) was investigated. 28373131 2 44 theme cartilage 419:427 arg1 protein 447:453 cartilage oligomeric matrix protein 419:453 cartilage oligomeric matrix protein (COMP) 419:460 Given that adherence of the lubricating protein, lubricin, to the cartilage surface is critical for boundary lubrication, an interaction with cartilage oligomeric matrix protein (COMP) was investigated. 28373131 5 45 theme inter-protein 864:876 arg1 bonds 888:892 inter-protein disulfide bonds 864:892 inter-protein disulfide bonds 864:892 Recombinant (RC) COMP and lubricin fragments were expressed to characterize this bonding and mass spectrometry employed to specifically identify the cysteines involved in inter-protein disulfide bonds. 28373131 11 46 theme rheumatoid 1832:1841 arg1 RA 1854:1855 RA 1854:1855 RA 1854:1855 This complex between lubricin and the cartilage protein COMP can be identified in the SF of patients with arthritis conditions including osteoarthritis (OA) and rheumatoid arthritis (RA). 28373131 11 46 theme rheumatoid 1832:1841 arg1 arthritis 1843:1851 rheumatoid arthritis 1832:1851 rheumatoid arthritis (RA) 1832:1856 This complex between lubricin and the cartilage protein COMP can be identified in the SF of patients with arthritis conditions including osteoarthritis (OA) and rheumatoid arthritis (RA). 28373131 10 47 theme complex 1597:1603 arg1 network 1605:1611 a complex network 1595:1611 a complex network with COMP involving both non-covalent and covalent bonds 1595:1668 CONCLUSION These data demonstrate that lubricin forms a complex network with COMP involving both non-covalent and covalent bonds. 28373131 7 48 theme solid-phase 1047:1057 arg1 assays 1067:1072 RC fragment solid-phase binding assays 1035:1072 RC fragment solid-phase binding assays 1035:1072 RC fragment solid-phase binding assays showed that the C-terminal (amino acids (AA) 518-757) of COMP bound non-covalently to the N-terminal of lubricin (AA 105-202). 28373131 5 49 theme mass 786:789 arg1 spectrometry 791:802 mass spectrometry 786:802 mass spectrometry 786:802 Recombinant (RC) COMP and lubricin fragments were expressed to characterize this bonding and mass spectrometry employed to specifically identify the cysteines involved in inter-protein disulfide bonds. 28373131 6 50 theme patients 966:973 arg1 SF 950:951 the SF 946:951 the SF of arthritic patients 946:973 RESULTS COMP-lubricin complexes were identified in the SF of arthritic patients by Western blot, co-immunoprecipitation and sandwich ELISA. 28373131 10 51 dep CONCLUSION 1541:1550 arg1 demonstrate 1563:1573 demonstrate 1563:1573 demonstrate that lubricin forms a complex network with COMP involving both non-covalent and covalent bonds 1563:1668 CONCLUSION These data demonstrate that lubricin forms a complex network with COMP involving both non-covalent and covalent bonds. 28373131 10 52 with network 1605:1611 arg1 COMP 1618:1621 COMP 1618:1621 COMP involving both non-covalent and covalent bonds 1618:1668 CONCLUSION These data demonstrate that lubricin forms a complex network with COMP involving both non-covalent and covalent bonds. 28373131 7 53 theme binding 1059:1065 arg1 assays 1067:1072 RC fragment solid-phase binding assays 1035:1072 RC fragment solid-phase binding assays 1035:1072 RC fragment solid-phase binding assays showed that the C-terminal (amino acids (AA) 518-757) of COMP bound non-covalently to the N-terminal of lubricin (AA 105-202). 28373131 1 54 theme OBJECTIVE 127:135 arg1 Understanding 137:149 OBJECTIVE Understanding 127:149 OBJECTIVE Understanding 127:149 OBJECTIVE Understanding the cartilage surface structure, lost in arthritic disease, is essential for developing strategies to effectively restore it. 28373131 6 55 theme arthritic 956:964 arg1 patients 966:973 arthritic patients 956:973 arthritic patients 956:973 RESULTS COMP-lubricin complexes were identified in the SF of arthritic patients by Western blot, co-immunoprecipitation and sandwich ELISA. 28373131 7 56 theme RC 1035:1036 arg1 assays 1067:1072 RC fragment solid-phase binding assays 1035:1072 RC fragment solid-phase binding assays 1035:1072 RC fragment solid-phase binding assays showed that the C-terminal (amino acids (AA) 518-757) of COMP bound non-covalently to the N-terminal of lubricin (AA 105-202). 28373131 2 57 theme cartilage 343:351 arg1 surface 353:359 the cartilage surface 339:359 the cartilage surface 339:359 Given that adherence of the lubricating protein, lubricin, to the cartilage surface is critical for boundary lubrication, an interaction with cartilage oligomeric matrix protein (COMP) was investigated. 28373131 1 58 theme surface 165:171 arg1 structure 173:181 the cartilage surface structure 151:181 the cartilage surface structure 151:181 OBJECTIVE Understanding the cartilage surface structure, lost in arthritic disease, is essential for developing strategies to effectively restore it. 28373131 7 59 theme fragment 1038:1045 arg1 assays 1067:1072 RC fragment solid-phase binding assays 1035:1072 RC fragment solid-phase binding assays 1035:1072 RC fragment solid-phase binding assays showed that the C-terminal (amino acids (AA) 518-757) of COMP bound non-covalently to the N-terminal of lubricin (AA 105-202). 28373131 9 60 theme disulfide 1439:1447 arg1 domains 1457:1463 the non-covalent and disulfide binding domains 1418:1463 domains 1457:1463 The close proximity of the non-covalent and disulfide binding domains on lubricin suggest a two-step mechanism to strongly bind lubricin to COMP. 28373131 5 61 theme Recombinant 693:703 arg1 COMP 710:713 Recombinant (RC) COMP and lubricin fragments 693:736 COMP 710:713 Recombinant (RC) COMP and lubricin fragments were expressed to characterize this bonding and mass spectrometry employed to specifically identify the cysteines involved in inter-protein disulfide bonds. 28373131 11 62 with patients 1763:1770 arg1 arthritis 1843:1851 rheumatoid arthritis 1832:1851 rheumatoid arthritis (RA) 1832:1856 This complex between lubricin and the cartilage protein COMP can be identified in the SF of patients with arthritis conditions including osteoarthritis (OA) and rheumatoid arthritis (RA). 28373131 11 62 with patients 1763:1770 arg1 osteoarthritis 1808:1821 osteoarthritis 1808:1821 osteoarthritis (OA) 1808:1826 This complex between lubricin and the cartilage protein COMP can be identified in the SF of patients with arthritis conditions including osteoarthritis (OA) and rheumatoid arthritis (RA). 28373131 11 62 with patients 1763:1770 arg1 conditions 1787:1796 arthritis conditions 1777:1796 arthritis conditions including osteoarthritis (OA) and rheumatoid arthritis (RA) 1777:1856 This complex between lubricin and the cartilage protein COMP can be identified in the SF of patients with arthritis conditions including osteoarthritis (OA) and rheumatoid arthritis (RA). 28373131 1 63 theme cartilage 155:163 arg1 structure 173:181 the cartilage surface structure 151:181 the cartilage surface structure 151:181 OBJECTIVE Understanding the cartilage surface structure, lost in arthritic disease, is essential for developing strategies to effectively restore it. 28373131 4 64 from patients 606:613 arg1 SF 587:588 SF 587:588 SF 587:588 DESIGN Synovial fluid (SF) from arthritic patients was used to detect possible COMP-lubricin complexes by immunological methods. 28373131 4 64 from patients 606:613 arg1 fluid 580:584 DESIGN Synovial fluid 564:584 DESIGN Synovial fluid (SF) from arthritic patients 564:613 DESIGN Synovial fluid (SF) from arthritic patients was used to detect possible COMP-lubricin complexes by immunological methods. 28373131 0 65 with complexes 50:58 arg1 lubricin 74:81 synovial lubricin 65:81 synovial lubricin 65:81 Cartilage oligomeric matrix protein forms protein complexes with synovial lubricin via non-covalent and covalent interactions. 28373131 2 66 theme boundary 377:384 arg1 lubrication 386:396 boundary lubrication 377:396 boundary lubrication 377:396 Given that adherence of the lubricating protein, lubricin, to the cartilage surface is critical for boundary lubrication, an interaction with cartilage oligomeric matrix protein (COMP) was investigated. 28373131 4 67 theme possible 634:641 arg1 complexes 657:665 possible COMP-lubricin complexes 634:665 possible COMP-lubricin complexes 634:665 DESIGN Synovial fluid (SF) from arthritic patients was used to detect possible COMP-lubricin complexes by immunological methods. 28373131 0 68 theme synovial 65:72 arg1 lubricin 74:81 synovial lubricin 65:81 synovial lubricin 65:81 Cartilage oligomeric matrix protein forms protein complexes with synovial lubricin via non-covalent and covalent interactions. 28373131 7 69 theme lubricin 1178:1185 arg1 N-terminal 1164:1173 N-terminal 1164:1173 N-terminal 1164:1173 RC fragment solid-phase binding assays showed that the C-terminal (amino acids (AA) 518-757) of COMP bound non-covalently to the N-terminal of lubricin (AA 105-202). 28373131 4 70 theme immunological 670:682 arg1 methods 684:690 immunological methods 670:690 immunological methods 670:690 DESIGN Synovial fluid (SF) from arthritic patients was used to detect possible COMP-lubricin complexes by immunological methods. 28373131 9 71 theme close 1399:1403 arg1 proximity 1405:1413 The close proximity 1395:1413 The close proximity of the non-covalent and disulfide binding domains on lubricin 1395:1475 The close proximity of the non-covalent and disulfide binding domains on lubricin suggest a two-step mechanism to strongly bind lubricin to COMP. 28373131 4 72 theme arthritic 596:604 arg1 patients 606:613 arthritic patients 596:613 arthritic patients 596:613 DESIGN Synovial fluid (SF) from arthritic patients was used to detect possible COMP-lubricin complexes by immunological methods. 28031745 12 0 theme sugarcane 1755:1763 arg1 alteration 1741:1750 the alteration 1737:1750 the alteration of sugarcane for improved lignocellulosic ethanol production 1737:1811 CONCLUSIONS Along with improvements in bagasse quality for the production of lignocellulosic-based fuels, there was only one line with reduction in juice sucrose extraction, and three lines with significantly improved sucrose production, providing evidence that the alteration of sugarcane for improved lignocellulosic ethanol production can be achieved without negatively impacting sugar production and perhaps even enhancing it. 28031745 11 1 theme improved 1402:1409 arg1 release 1419:1425 improved glucose release 1402:1425 improved glucose release (F5H-2 and COMT-2) 1402:1444 Two of the lines with improved glucose release (F5H-2 and COMT-2) also had reduced S:G ratios. 28031745 3 2 contain has 391:393 arg2 potential 395:403 potential 395:403 potential 395:403 Residual bagasse following sucrose extraction is currently underutilized and it has potential as a carbohydrate source for the production of biofuels. 28031745 3 2 contain has 391:393 arg1 it 388:389 it 388:389 it 388:389 Residual bagasse following sucrose extraction is currently underutilized and it has potential as a carbohydrate source for the production of biofuels. 28031745 3 2 contain has 391:393 arg2 source 423:428 a carbohydrate source 408:428 a carbohydrate source for the production of biofuels 408:459 Residual bagasse following sucrose extraction is currently underutilized and it has potential as a carbohydrate source for the production of biofuels. 28031745 11 3 theme lines 1391:1395 arg1 Two 1380:1382 Two 1380:1382 Two 1380:1382 Two of the lines with improved glucose release (F5H-2 and COMT-2) also had reduced S:G ratios. 28031745 11 3 theme lines 1391:1395 arg1 lines 1391:1395 the lines 1387:1395 the lines with improved glucose release (F5H-2 and COMT-2) 1387:1444 Two of the lines with improved glucose release (F5H-2 and COMT-2) also had reduced S:G ratios. 28031745 6 4 theme caffeic 829:835 arg1 COMT 863:866 COMT 863:866 COMT 863:866 These genes, caffeoyl-CoA O-methyltransferase (CCoAOMT), ferulate 5-hydroxylase (F5H) and caffeic acid O-methyltransferase (COMT), impact lignin content and/or composition. 28031745 6 4 theme caffeic 829:835 arg1 O-methyltransferase 842:860 caffeic acid O-methyltransferase 829:860 caffeic acid O-methyltransferase (COMT) 829:867 These genes, caffeoyl-CoA O-methyltransferase (CCoAOMT), ferulate 5-hydroxylase (F5H) and caffeic acid O-methyltransferase (COMT), impact lignin content and/or composition. 28031745 12 5 from improvements 1498:1509 arg1 quality 1522:1528 bagasse quality 1514:1528 bagasse quality for the production of lignocellulosic-based fuels 1514:1578 CONCLUSIONS Along with improvements in bagasse quality for the production of lignocellulosic-based fuels, there was only one line with reduction in juice sucrose extraction, and three lines with significantly improved sucrose production, providing evidence that the alteration of sugarcane for improved lignocellulosic ethanol production can be achieved without negatively impacting sugar production and perhaps even enhancing it. 28031745 12 6 with lines 1659:1663 arg1 production 1701:1710 significantly improved sucrose production 1670:1710 significantly improved sucrose production 1670:1710 CONCLUSIONS Along with improvements in bagasse quality for the production of lignocellulosic-based fuels, there was only one line with reduction in juice sucrose extraction, and three lines with significantly improved sucrose production, providing evidence that the alteration of sugarcane for improved lignocellulosic ethanol production can be achieved without negatively impacting sugar production and perhaps even enhancing it. 28031745 12 6 with lines 1659:1663 arg1 reduction 1610:1618 reduction 1610:1618 reduction in juice sucrose extraction 1610:1646 CONCLUSIONS Along with improvements in bagasse quality for the production of lignocellulosic-based fuels, there was only one line with reduction in juice sucrose extraction, and three lines with significantly improved sucrose production, providing evidence that the alteration of sugarcane for improved lignocellulosic ethanol production can be achieved without negatively impacting sugar production and perhaps even enhancing it. 28031745 12 7 theme sugar 1858:1862 arg1 production 1864:1873 sugar production 1858:1873 sugar production 1858:1873 CONCLUSIONS Along with improvements in bagasse quality for the production of lignocellulosic-based fuels, there was only one line with reduction in juice sucrose extraction, and three lines with significantly improved sucrose production, providing evidence that the alteration of sugarcane for improved lignocellulosic ethanol production can be achieved without negatively impacting sugar production and perhaps even enhancing it. 28031745 10 8 theme reduced 1267:1273 arg1 content 1282:1288 reduced lignin content 1267:1288 reduced lignin content 1267:1288 For COMT, one line had reduced lignin content, and this line and another released higher levels of glucose during enzymatic hydrolysis. 28031745 4 9 theme efforts 596:602 arg1 focus 576:580 the focus 572:580 the focus of transgenic efforts 572:602 As with all lignocellulosic crops, lignin acts as a barrier to accessing the polysaccharides, and as such, is the focus of transgenic efforts. 28031745 1 10 theme biomass 197:203 arg1 annually 205:212 biomass annually 197:212 biomass annually 197:212 BACKGROUND Sugarcane is a subtropical crop that produces large amounts of biomass annually. 28031745 8 11 theme improved 1120:1127 arg1 release 1137:1143 improved glucose release 1120:1143 improved glucose release 1120:1143 For the CCoAOMT lines, there were no lines with a reduction in lignin content and only one line showed improved glucose release. 28031745 6 12 theme lignin 877:882 arg1 content 884:890 impact lignin content 870:890 impact lignin content 870:890 These genes, caffeoyl-CoA O-methyltransferase (CCoAOMT), ferulate 5-hydroxylase (F5H) and caffeic acid O-methyltransferase (COMT), impact lignin content and/or composition. 28031745 12 13 theme lignocellulosic-based 1552:1572 arg1 fuels 1574:1578 lignocellulosic-based fuels 1552:1578 lignocellulosic-based fuels 1552:1578 CONCLUSIONS Along with improvements in bagasse quality for the production of lignocellulosic-based fuels, there was only one line with reduction in juice sucrose extraction, and three lines with significantly improved sucrose production, providing evidence that the alteration of sugarcane for improved lignocellulosic ethanol production can be achieved without negatively impacting sugar production and perhaps even enhancing it. 28031745 6 14 theme caffeoyl-CoA 752:763 arg1 CCoAOMT 786:792 CCoAOMT 786:792 CCoAOMT 786:792 These genes, caffeoyl-CoA O-methyltransferase (CCoAOMT), ferulate 5-hydroxylase (F5H) and caffeic acid O-methyltransferase (COMT), impact lignin content and/or composition. 28031745 6 14 theme caffeoyl-CoA 752:763 arg1 genes 745:749 These genes 739:749 These genes 739:749 These genes, caffeoyl-CoA O-methyltransferase (CCoAOMT), ferulate 5-hydroxylase (F5H) and caffeic acid O-methyltransferase (COMT), impact lignin content and/or composition. 28031745 6 14 theme caffeoyl-CoA 752:763 arg1 O-methyltransferase 765:783 caffeoyl-CoA O-methyltransferase 752:783 caffeoyl-CoA O-methyltransferase (CCoAOMT) 752:793 These genes, caffeoyl-CoA O-methyltransferase (CCoAOMT), ferulate 5-hydroxylase (F5H) and caffeic acid O-methyltransferase (COMT), impact lignin content and/or composition. 28031745 7 15 theme RNAi 929:932 arg1 construct 934:942 each RNAi construct 924:942 each RNAi construct 924:942 RESULTS For each RNAi construct, we selected three events for further analysis based on qRT-PCR results. 28031745 12 16 with line 1600:1603 arg1 production 1701:1710 significantly improved sucrose production 1670:1710 significantly improved sucrose production 1670:1710 CONCLUSIONS Along with improvements in bagasse quality for the production of lignocellulosic-based fuels, there was only one line with reduction in juice sucrose extraction, and three lines with significantly improved sucrose production, providing evidence that the alteration of sugarcane for improved lignocellulosic ethanol production can be achieved without negatively impacting sugar production and perhaps even enhancing it. 28031745 12 16 with line 1600:1603 arg1 reduction 1610:1618 reduction 1610:1618 reduction in juice sucrose extraction 1610:1646 CONCLUSIONS Along with improvements in bagasse quality for the production of lignocellulosic-based fuels, there was only one line with reduction in juice sucrose extraction, and three lines with significantly improved sucrose production, providing evidence that the alteration of sugarcane for improved lignocellulosic ethanol production can be achieved without negatively impacting sugar production and perhaps even enhancing it. 28031745 3 17 theme Residual 311:318 arg1 bagasse 320:326 Residual bagasse 311:326 Residual bagasse following sucrose extraction 311:355 Residual bagasse following sucrose extraction is currently underutilized and it has potential as a carbohydrate source for the production of biofuels. 28031745 7 18 dep RESULTS 912:918 arg1 selected 948:955 selected 948:955 selected three events for further analysis based on qRT-PCR results 948:1014 RESULTS For each RNAi construct, we selected three events for further analysis based on qRT-PCR results. 28031745 5 19 theme lignin 697:702 arg1 pathway 717:723 the lignin biosynthetic pathway 693:723 the lignin biosynthetic pathway in sugarcane 693:736 In this study, we used RNAi to individually reduce the expression of three key genes in the lignin biosynthetic pathway in sugarcane. 28031745 2 20 theme agricultural 227:238 arg1 crop 240:243 a key agricultural crop 221:243 a key agricultural crop in many countries for the production of sugar and other products 221:308 It is a key agricultural crop in many countries for the production of sugar and other products. 28031745 2 20 theme agricultural 227:238 arg1 It 215:216 It 215:216 It 215:216 It is a key agricultural crop in many countries for the production of sugar and other products. 28031745 9 21 contain had 1164:1166 arg1 lines 1158:1162 no lines 1155:1162 no lines 1155:1162 For F5H, no lines had reduced lignin, but one line had a significant increase in glucose release. 28031745 9 21 contain had 1164:1166 arg2 lignin 1176:1181 reduced lignin 1168:1181 reduced lignin 1168:1181 For F5H, no lines had reduced lignin, but one line had a significant increase in glucose release. 28031745 0 22 theme glucose 68:74 arg1 release 76:82 glucose release 68:82 glucose release 68:82 RNAi downregulation of three key lignin genes in sugarcane improves glucose release without reduction in sugar production. 28031745 5 23 theme key 680:682 arg1 genes 684:688 three key genes 674:688 three key genes 674:688 In this study, we used RNAi to individually reduce the expression of three key genes in the lignin biosynthetic pathway in sugarcane. 28031745 12 24 theme lignocellulosic 1778:1792 arg1 production 1802:1811 improved lignocellulosic ethanol production 1769:1811 improved lignocellulosic ethanol production 1769:1811 CONCLUSIONS Along with improvements in bagasse quality for the production of lignocellulosic-based fuels, there was only one line with reduction in juice sucrose extraction, and three lines with significantly improved sucrose production, providing evidence that the alteration of sugarcane for improved lignocellulosic ethanol production can be achieved without negatively impacting sugar production and perhaps even enhancing it. 28031745 12 25 theme bagasse 1514:1520 arg1 quality 1522:1528 bagasse quality 1514:1528 bagasse quality for the production of lignocellulosic-based fuels 1514:1578 CONCLUSIONS Along with improvements in bagasse quality for the production of lignocellulosic-based fuels, there was only one line with reduction in juice sucrose extraction, and three lines with significantly improved sucrose production, providing evidence that the alteration of sugarcane for improved lignocellulosic ethanol production can be achieved without negatively impacting sugar production and perhaps even enhancing it. 28031745 12 26 from reduction 1610:1618 arg1 extraction 1637:1646 juice sucrose extraction 1623:1646 juice sucrose extraction 1623:1646 CONCLUSIONS Along with improvements in bagasse quality for the production of lignocellulosic-based fuels, there was only one line with reduction in juice sucrose extraction, and three lines with significantly improved sucrose production, providing evidence that the alteration of sugarcane for improved lignocellulosic ethanol production can be achieved without negatively impacting sugar production and perhaps even enhancing it. 28031745 10 27 theme higher 1326:1331 arg1 levels 1333:1338 higher levels 1326:1338 higher levels of glucose 1326:1349 For COMT, one line had reduced lignin content, and this line and another released higher levels of glucose during enzymatic hydrolysis. 28031745 3 28 theme carbohydrate 410:421 arg1 potential 395:403 potential 395:403 potential 395:403 Residual bagasse following sucrose extraction is currently underutilized and it has potential as a carbohydrate source for the production of biofuels. 28031745 3 28 theme carbohydrate 410:421 arg1 source 423:428 a carbohydrate source 408:428 a carbohydrate source for the production of biofuels 408:459 Residual bagasse following sucrose extraction is currently underutilized and it has potential as a carbohydrate source for the production of biofuels. 28031745 0 29 theme RNAi 0:3 arg1 downregulation 5:18 RNAi downregulation 0:18 RNAi downregulation of three key lignin genes in sugarcane 0:57 RNAi downregulation of three key lignin genes in sugarcane improves glucose release without reduction in sugar production. 28031745 2 30 from crop 240:243 arg1 countries 253:261 many countries 248:261 many countries 248:261 It is a key agricultural crop in many countries for the production of sugar and other products. 28031745 3 31 theme biofuels 452:459 arg1 production 438:447 the production 434:447 the production of biofuels 434:459 Residual bagasse following sucrose extraction is currently underutilized and it has potential as a carbohydrate source for the production of biofuels. 28031745 9 32 theme glucose 1227:1233 arg1 release 1235:1241 glucose release 1227:1241 glucose release 1227:1241 For F5H, no lines had reduced lignin, but one line had a significant increase in glucose release. 28031745 0 33 theme key 29:31 arg1 genes 40:44 three key lignin genes 23:44 three key lignin genes 23:44 RNAi downregulation of three key lignin genes in sugarcane improves glucose release without reduction in sugar production. 28031745 12 34 dep CONCLUSIONS 1475:1485 arg1 was 1587:1589 was 1587:1589 was 1587:1589 CONCLUSIONS Along with improvements in bagasse quality for the production of lignocellulosic-based fuels, there was only one line with reduction in juice sucrose extraction, and three lines with significantly improved sucrose production, providing evidence that the alteration of sugarcane for improved lignocellulosic ethanol production can be achieved without negatively impacting sugar production and perhaps even enhancing it. 28031745 0 35 theme genes 40:44 arg1 downregulation 5:18 RNAi downregulation 0:18 RNAi downregulation of three key lignin genes in sugarcane 0:57 RNAi downregulation of three key lignin genes in sugarcane improves glucose release without reduction in sugar production. 28031745 12 36 theme sucrose 1693:1699 arg1 production 1701:1710 significantly improved sucrose production 1670:1710 significantly improved sucrose production 1670:1710 CONCLUSIONS Along with improvements in bagasse quality for the production of lignocellulosic-based fuels, there was only one line with reduction in juice sucrose extraction, and three lines with significantly improved sucrose production, providing evidence that the alteration of sugarcane for improved lignocellulosic ethanol production can be achieved without negatively impacting sugar production and perhaps even enhancing it. 28031745 12 37 theme sucrose 1629:1635 arg1 extraction 1637:1646 juice sucrose extraction 1623:1646 juice sucrose extraction 1623:1646 CONCLUSIONS Along with improvements in bagasse quality for the production of lignocellulosic-based fuels, there was only one line with reduction in juice sucrose extraction, and three lines with significantly improved sucrose production, providing evidence that the alteration of sugarcane for improved lignocellulosic ethanol production can be achieved without negatively impacting sugar production and perhaps even enhancing it. 28031745 11 38 theme G 1465:1465 arg1 ratios 1467:1472 reduced S:G ratios 1455:1472 reduced S:G ratios 1455:1472 Two of the lines with improved glucose release (F5H-2 and COMT-2) also had reduced S:G ratios. 28031745 10 39 contain had 1263:1265 arg2 content 1282:1288 reduced lignin content 1267:1288 reduced lignin content 1267:1288 For COMT, one line had reduced lignin content, and this line and another released higher levels of glucose during enzymatic hydrolysis. 28031745 10 39 contain had 1263:1265 arg1 line 1258:1261 one line 1254:1261 one line 1254:1261 For COMT, one line had reduced lignin content, and this line and another released higher levels of glucose during enzymatic hydrolysis. 28031745 11 40 dep release 1419:1425 arg1 COMT-2 1438:1443 COMT-2 1438:1443 COMT-2 1438:1443 Two of the lines with improved glucose release (F5H-2 and COMT-2) also had reduced S:G ratios. 28031745 11 40 dep release 1419:1425 arg1 F5H-2 1428:1432 F5H-2 1428:1432 F5H-2 1428:1432 Two of the lines with improved glucose release (F5H-2 and COMT-2) also had reduced S:G ratios. 28031745 11 41 theme S 1463:1463 arg1 ratios 1467:1472 reduced S:G ratios 1455:1472 reduced S:G ratios 1455:1472 Two of the lines with improved glucose release (F5H-2 and COMT-2) also had reduced S:G ratios. 28031745 5 42 from expression 660:669 arg1 pathway 717:723 the lignin biosynthetic pathway 693:723 the lignin biosynthetic pathway in sugarcane 693:736 In this study, we used RNAi to individually reduce the expression of three key genes in the lignin biosynthetic pathway in sugarcane. 28031745 11 43 theme glucose 1411:1417 arg1 release 1419:1425 improved glucose release 1402:1425 improved glucose release (F5H-2 and COMT-2) 1402:1444 Two of the lines with improved glucose release (F5H-2 and COMT-2) also had reduced S:G ratios. 28031745 6 44 theme acid 837:840 arg1 COMT 863:866 COMT 863:866 COMT 863:866 These genes, caffeoyl-CoA O-methyltransferase (CCoAOMT), ferulate 5-hydroxylase (F5H) and caffeic acid O-methyltransferase (COMT), impact lignin content and/or composition. 28031745 6 44 theme acid 837:840 arg1 O-methyltransferase 842:860 caffeic acid O-methyltransferase 829:860 caffeic acid O-methyltransferase (COMT) 829:867 These genes, caffeoyl-CoA O-methyltransferase (CCoAOMT), ferulate 5-hydroxylase (F5H) and caffeic acid O-methyltransferase (COMT), impact lignin content and/or composition. 28031745 6 45 theme impact 870:875 arg1 content 884:890 impact lignin content 870:890 impact lignin content 870:890 These genes, caffeoyl-CoA O-methyltransferase (CCoAOMT), ferulate 5-hydroxylase (F5H) and caffeic acid O-methyltransferase (COMT), impact lignin content and/or composition. 28031745 8 46 theme lignin 1080:1085 arg1 content 1087:1093 lignin content 1080:1093 lignin content 1080:1093 For the CCoAOMT lines, there were no lines with a reduction in lignin content and only one line showed improved glucose release. 28031745 2 47 theme other 295:299 arg1 products 301:308 other products 295:308 other products 295:308 It is a key agricultural crop in many countries for the production of sugar and other products. 28031745 1 48 theme large 180:184 arg1 amounts 186:192 large amounts 180:192 large amounts of biomass annually 180:212 BACKGROUND Sugarcane is a subtropical crop that produces large amounts of biomass annually. 28031745 1 48 theme large 180:184 arg1 annually 205:212 biomass annually 197:212 biomass annually 197:212 BACKGROUND Sugarcane is a subtropical crop that produces large amounts of biomass annually. 28031745 7 49 theme qRT-PCR 1000:1006 arg1 results 1008:1014 qRT-PCR results 1000:1014 qRT-PCR results 1000:1014 RESULTS For each RNAi construct, we selected three events for further analysis based on qRT-PCR results. 28031745 10 50 theme lignin 1275:1280 arg1 content 1282:1288 reduced lignin content 1267:1288 reduced lignin content 1267:1288 For COMT, one line had reduced lignin content, and this line and another released higher levels of glucose during enzymatic hydrolysis. 28031745 2 51 theme sugar 285:289 arg1 production 271:280 the production 267:280 the production of sugar and other products 267:308 It is a key agricultural crop in many countries for the production of sugar and other products. 28031745 5 52 used used 623:626 arg2 we 620:621 we 620:621 we 620:621 In this study, we used RNAi to individually reduce the expression of three key genes in the lignin biosynthetic pathway in sugarcane. 28031745 4 53 theme transgenic 585:594 arg1 efforts 596:602 transgenic efforts 585:602 transgenic efforts 585:602 As with all lignocellulosic crops, lignin acts as a barrier to accessing the polysaccharides, and as such, is the focus of transgenic efforts. 28031745 2 54 theme key 223:225 arg1 crop 240:243 a key agricultural crop 221:243 a key agricultural crop in many countries for the production of sugar and other products 221:308 It is a key agricultural crop in many countries for the production of sugar and other products. 28031745 2 54 theme key 223:225 arg1 It 215:216 It 215:216 It 215:216 It is a key agricultural crop in many countries for the production of sugar and other products. 28031745 1 55 theme annually 205:212 arg1 amounts 186:192 large amounts 180:192 large amounts of biomass annually 180:212 BACKGROUND Sugarcane is a subtropical crop that produces large amounts of biomass annually. 28031745 1 55 theme annually 205:212 arg1 annually 205:212 biomass annually 197:212 biomass annually 197:212 BACKGROUND Sugarcane is a subtropical crop that produces large amounts of biomass annually. 28031745 7 56 theme further 974:980 arg1 analysis 982:989 further analysis 974:989 further analysis based on qRT-PCR results 974:1014 RESULTS For each RNAi construct, we selected three events for further analysis based on qRT-PCR results. 28031745 8 57 theme glucose 1129:1135 arg1 release 1137:1143 improved glucose release 1120:1143 improved glucose release 1120:1143 For the CCoAOMT lines, there were no lines with a reduction in lignin content and only one line showed improved glucose release. 28031745 11 58 contain had 1451:1453 arg1 Two 1380:1382 Two 1380:1382 Two 1380:1382 Two of the lines with improved glucose release (F5H-2 and COMT-2) also had reduced S:G ratios. 28031745 11 58 contain had 1451:1453 arg1 lines 1391:1395 the lines 1387:1395 the lines with improved glucose release (F5H-2 and COMT-2) 1387:1444 Two of the lines with improved glucose release (F5H-2 and COMT-2) also had reduced S:G ratios. 28031745 11 58 contain had 1451:1453 arg2 ratios 1467:1472 reduced S:G ratios 1455:1472 reduced S:G ratios 1455:1472 Two of the lines with improved glucose release (F5H-2 and COMT-2) also had reduced S:G ratios. 28031745 5 59 from pathway 717:723 arg1 sugarcane 728:736 sugarcane 728:736 sugarcane 728:736 In this study, we used RNAi to individually reduce the expression of three key genes in the lignin biosynthetic pathway in sugarcane. 28031745 2 60 theme many 248:251 arg1 countries 253:261 many countries 248:261 many countries 248:261 It is a key agricultural crop in many countries for the production of sugar and other products. 28031745 1 61 theme BACKGROUND 123:132 arg1 Sugarcane 134:142 BACKGROUND Sugarcane 123:142 BACKGROUND Sugarcane 123:142 BACKGROUND Sugarcane is a subtropical crop that produces large amounts of biomass annually. 28031745 1 61 theme BACKGROUND 123:132 arg1 crop 161:164 a subtropical crop 147:164 a subtropical crop that produces large amounts of biomass annually 147:212 BACKGROUND Sugarcane is a subtropical crop that produces large amounts of biomass annually. 28031745 0 62 from reduction 92:100 arg1 production 111:120 sugar production 105:120 sugar production 105:120 RNAi downregulation of three key lignin genes in sugarcane improves glucose release without reduction in sugar production. 28031745 9 63 theme reduced 1168:1174 arg1 lignin 1176:1181 reduced lignin 1168:1181 reduced lignin 1168:1181 For F5H, no lines had reduced lignin, but one line had a significant increase in glucose release. 28031745 12 64 theme fuels 1574:1578 arg1 production 1538:1547 the production 1534:1547 the production of lignocellulosic-based fuels 1534:1578 CONCLUSIONS Along with improvements in bagasse quality for the production of lignocellulosic-based fuels, there was only one line with reduction in juice sucrose extraction, and three lines with significantly improved sucrose production, providing evidence that the alteration of sugarcane for improved lignocellulosic ethanol production can be achieved without negatively impacting sugar production and perhaps even enhancing it. 28031745 5 65 theme biosynthetic 704:715 arg1 pathway 717:723 the lignin biosynthetic pathway 693:723 the lignin biosynthetic pathway in sugarcane 693:736 In this study, we used RNAi to individually reduce the expression of three key genes in the lignin biosynthetic pathway in sugarcane. 28031745 12 66 theme improved 1769:1776 arg1 production 1802:1811 improved lignocellulosic ethanol production 1769:1811 improved lignocellulosic ethanol production 1769:1811 CONCLUSIONS Along with improvements in bagasse quality for the production of lignocellulosic-based fuels, there was only one line with reduction in juice sucrose extraction, and three lines with significantly improved sucrose production, providing evidence that the alteration of sugarcane for improved lignocellulosic ethanol production can be achieved without negatively impacting sugar production and perhaps even enhancing it. 28031745 1 67 theme subtropical 149:159 arg1 Sugarcane 134:142 BACKGROUND Sugarcane 123:142 BACKGROUND Sugarcane 123:142 BACKGROUND Sugarcane is a subtropical crop that produces large amounts of biomass annually. 28031745 1 67 theme subtropical 149:159 arg1 crop 161:164 a subtropical crop 147:164 a subtropical crop that produces large amounts of biomass annually 147:212 BACKGROUND Sugarcane is a subtropical crop that produces large amounts of biomass annually. 28031745 0 68 from downregulation 5:18 arg1 sugarcane 49:57 sugarcane 49:57 sugarcane 49:57 RNAi downregulation of three key lignin genes in sugarcane improves glucose release without reduction in sugar production. 28031745 12 69 theme ethanol 1794:1800 arg1 production 1802:1811 improved lignocellulosic ethanol production 1769:1811 improved lignocellulosic ethanol production 1769:1811 CONCLUSIONS Along with improvements in bagasse quality for the production of lignocellulosic-based fuels, there was only one line with reduction in juice sucrose extraction, and three lines with significantly improved sucrose production, providing evidence that the alteration of sugarcane for improved lignocellulosic ethanol production can be achieved without negatively impacting sugar production and perhaps even enhancing it. 28031745 0 70 theme sugar 105:109 arg1 production 111:120 sugar production 105:120 sugar production 105:120 RNAi downregulation of three key lignin genes in sugarcane improves glucose release without reduction in sugar production. 28031745 3 71 theme sucrose 338:344 arg1 extraction 346:355 sucrose extraction 338:355 sucrose extraction 338:355 Residual bagasse following sucrose extraction is currently underutilized and it has potential as a carbohydrate source for the production of biofuels. 28031745 4 72 theme lignocellulosic 474:488 arg1 crops 490:494 all lignocellulosic crops 470:494 all lignocellulosic crops 470:494 As with all lignocellulosic crops, lignin acts as a barrier to accessing the polysaccharides, and as such, is the focus of transgenic efforts. 28031745 12 73 dep impacting 1848:1856 arg1 enhancing 1892:1900 enhancing 1892:1900 enhancing it 1892:1903 CONCLUSIONS Along with improvements in bagasse quality for the production of lignocellulosic-based fuels, there was only one line with reduction in juice sucrose extraction, and three lines with significantly improved sucrose production, providing evidence that the alteration of sugarcane for improved lignocellulosic ethanol production can be achieved without negatively impacting sugar production and perhaps even enhancing it. 28031745 5 74 theme genes 684:688 arg1 expression 660:669 the expression 656:669 the expression of three key genes in the lignin biosynthetic pathway in sugarcane 656:736 In this study, we used RNAi to individually reduce the expression of three key genes in the lignin biosynthetic pathway in sugarcane. 28031745 9 75 theme significant 1203:1213 arg1 increase 1215:1222 a significant increase 1201:1222 a significant increase in glucose release 1201:1241 For F5H, no lines had reduced lignin, but one line had a significant increase in glucose release. 28031745 9 76 from increase 1215:1222 arg1 release 1235:1241 glucose release 1227:1241 glucose release 1227:1241 For F5H, no lines had reduced lignin, but one line had a significant increase in glucose release. 28031745 10 77 theme enzymatic 1358:1366 arg1 hydrolysis 1368:1377 enzymatic hydrolysis 1358:1377 enzymatic hydrolysis 1358:1377 For COMT, one line had reduced lignin content, and this line and another released higher levels of glucose during enzymatic hydrolysis. 28031745 9 78 contain had 1197:1199 arg2 increase 1215:1222 a significant increase 1201:1222 a significant increase in glucose release 1201:1241 For F5H, no lines had reduced lignin, but one line had a significant increase in glucose release. 28031745 9 78 contain had 1197:1199 arg1 line 1192:1195 one line 1188:1195 one line 1188:1195 For F5H, no lines had reduced lignin, but one line had a significant increase in glucose release. 28031745 0 79 theme lignin 33:38 arg1 genes 40:44 three key lignin genes 23:44 three key lignin genes 23:44 RNAi downregulation of three key lignin genes in sugarcane improves glucose release without reduction in sugar production. 28031745 8 80 theme CCoAOMT 1025:1031 arg1 lines 1033:1037 the CCoAOMT lines 1021:1037 the CCoAOMT lines 1021:1037 For the CCoAOMT lines, there were no lines with a reduction in lignin content and only one line showed improved glucose release. 28031745 11 81 with lines 1391:1395 arg1 release 1419:1425 improved glucose release 1402:1425 improved glucose release (F5H-2 and COMT-2) 1402:1444 Two of the lines with improved glucose release (F5H-2 and COMT-2) also had reduced S:G ratios. 28031745 10 82 theme glucose 1343:1349 arg1 levels 1333:1338 higher levels 1326:1338 higher levels of glucose 1326:1349 For COMT, one line had reduced lignin content, and this line and another released higher levels of glucose during enzymatic hydrolysis. 28031745 12 83 theme improved 1684:1691 arg1 production 1701:1710 significantly improved sucrose production 1670:1710 significantly improved sucrose production 1670:1710 CONCLUSIONS Along with improvements in bagasse quality for the production of lignocellulosic-based fuels, there was only one line with reduction in juice sucrose extraction, and three lines with significantly improved sucrose production, providing evidence that the alteration of sugarcane for improved lignocellulosic ethanol production can be achieved without negatively impacting sugar production and perhaps even enhancing it. 28031745 2 84 theme products 301:308 arg1 production 271:280 the production 267:280 the production of sugar and other products 267:308 It is a key agricultural crop in many countries for the production of sugar and other products. 28031745 8 85 from reduction 1067:1075 arg1 content 1087:1093 lignin content 1080:1093 lignin content 1080:1093 For the CCoAOMT lines, there were no lines with a reduction in lignin content and only one line showed improved glucose release. 28031745 12 86 theme juice 1623:1627 arg1 extraction 1637:1646 juice sucrose extraction 1623:1646 juice sucrose extraction 1623:1646 CONCLUSIONS Along with improvements in bagasse quality for the production of lignocellulosic-based fuels, there was only one line with reduction in juice sucrose extraction, and three lines with significantly improved sucrose production, providing evidence that the alteration of sugarcane for improved lignocellulosic ethanol production can be achieved without negatively impacting sugar production and perhaps even enhancing it. 28031745 11 87 theme reduced 1455:1461 arg1 ratios 1467:1472 reduced S:G ratios 1455:1472 reduced S:G ratios 1455:1472 Two of the lines with improved glucose release (F5H-2 and COMT-2) also had reduced S:G ratios. 27983475 3 0 theme KRT 291:293 arg1 Cells 275:279 Cells 275:279 Cells of strain KRT 275:293 Cells of strain KRT were thin (0.2-0.3 µm), flexible, motile, Gram-stain-negative rods of variable length. 27983475 13 1 theme 16S 1228:1230 arg1 rRNA 1232:1235 16S rRNA 1228:1235 16S rRNA gene sequence analysis 1228:1258 16S rRNA gene sequence analysis placed isolate KRT in the phylum Calditrichaeota where it represented a novel species of a new genus, for which the name Calorithrix insularis gen. nov., sp. 27983475 8 2 theme Strain 774:779 arg1 KRT 781:783 Strain KRT 774:783 Strain KRT 774:783 Strain KRT did not need the presence of a reducing agent in the medium and tolerated the presence of oxygen in the gas phase up to 3 % (v/v). 27983475 8 3 attach presence 802:809 arg2 agent 825:829 a reducing agent 814:829 a reducing agent 814:829 Strain KRT did not need the presence of a reducing agent in the medium and tolerated the presence of oxygen in the gas phase up to 3 % (v/v). 27983475 8 3 attach presence 802:809 arg1 medium 838:843 the medium 834:843 the medium 834:843 Strain KRT did not need the presence of a reducing agent in the medium and tolerated the presence of oxygen in the gas phase up to 3 % (v/v). 27983475 5 4 theme substrates 510:519 arg1 polysaccharides 551:565 polysaccharides 551:565 polysaccharides 551:565 Strain KRT was able to ferment a wide range of proteinaceous substrates, pyruvate, and mono-, di- and polysaccharides. 27983475 5 4 theme substrates 510:519 arg1 di- 543:545 di- 543:545 di- 543:545 Strain KRT was able to ferment a wide range of proteinaceous substrates, pyruvate, and mono-, di- and polysaccharides. 27983475 5 4 theme substrates 510:519 arg1 pyruvate 522:529 pyruvate 522:529 pyruvate 522:529 Strain KRT was able to ferment a wide range of proteinaceous substrates, pyruvate, and mono-, di- and polysaccharides. 27983475 5 4 theme substrates 510:519 arg1 range 487:491 a wide range 480:491 a wide range of proteinaceous substrates 480:519 Strain KRT was able to ferment a wide range of proteinaceous substrates, pyruvate, and mono-, di- and polysaccharides. 27983475 5 4 theme substrates 510:519 arg1 mono- 536:540 mono- 536:540 mono- 536:540 Strain KRT was able to ferment a wide range of proteinaceous substrates, pyruvate, and mono-, di- and polysaccharides. 27983475 13 5 theme rRNA 1232:1235 arg1 analysis 1251:1258 16S rRNA gene sequence analysis 1228:1258 16S rRNA gene sequence analysis 1228:1258 16S rRNA gene sequence analysis placed isolate KRT in the phylum Calditrichaeota where it represented a novel species of a new genus, for which the name Calorithrix insularis gen. nov., sp. 27983475 13 6 dep sp 1414:1415 arg1 nov. 1408:1411 the name Calorithrix insularis gen. nov. 1372:1411 the name Calorithrix insularis gen. nov. 1372:1411 16S rRNA gene sequence analysis placed isolate KRT in the phylum Calditrichaeota where it represented a novel species of a new genus, for which the name Calorithrix insularis gen. nov., sp. 27983475 0 7 dep sp 33:34 arg1 nov. 27:30 Calorithrix insularis gen. nov. 0:30 Calorithrix insularis gen. nov. 0:30 Calorithrix insularis gen. nov., sp. 27983475 12 8 theme KRT 1209:1211 arg1 DNA 1195:1197 the genomic DNA 1183:1197 the genomic DNA of strain KRT 1183:1211 The G+C content of the genomic DNA of strain KRT was 47.3 mol%. 27983475 12 9 theme DNA 1195:1197 arg1 % 1225:1225 47.3 mol% 1217:1225 47.3 mol% 1217:1225 The G+C content of the genomic DNA of strain KRT was 47.3 mol%. 27983475 12 9 theme DNA 1195:1197 arg1 content 1172:1178 The G+C content 1164:1178 The G+C content of the genomic DNA of strain KRT 1164:1211 The G+C content of the genomic DNA of strain KRT was 47.3 mol%. 27983475 13 10 theme Calorithrix 1381:1391 arg1 nov. 1408:1411 the name Calorithrix insularis gen. nov. 1372:1411 the name Calorithrix insularis gen. nov. 1372:1411 16S rRNA gene sequence analysis placed isolate KRT in the phylum Calditrichaeota where it represented a novel species of a new genus, for which the name Calorithrix insularis gen. nov., sp. 27983475 12 11 theme genomic 1187:1193 arg1 DNA 1195:1197 the genomic DNA 1183:1197 the genomic DNA of strain KRT 1183:1211 The G+C content of the genomic DNA of strain KRT was 47.3 mol%. 27983475 11 12 theme Yeast 1112:1116 arg1 extract 1118:1124 Yeast extract 1112:1124 Yeast extract (0.05 g l-1) 1112:1137 Yeast extract (0.05 g l-1) was required for growth. 27983475 11 12 theme Yeast 1112:1116 arg1 l-1 1134:1136 0.05 g l-1 1127:1136 0.05 g l-1 1127:1136 Yeast extract (0.05 g l-1) was required for growth. 27983475 15 13 theme Calorithrix 1455:1465 arg1 insularis 1467:1475 Calorithrix insularis 1455:1475 Calorithrix insularis 1455:1475 The type strain of Calorithrix insularis is KRT (=DSM 101605T=VKM B-3022T). 27983475 12 14 theme strain 1202:1207 arg1 KRT 1209:1211 strain KRT 1202:1211 strain KRT 1202:1211 The G+C content of the genomic DNA of strain KRT was 47.3 mol%. 27983475 8 15 dep % 907:907 arg1 3  905:906 3  905:906 3  905:906 Strain KRT did not need the presence of a reducing agent in the medium and tolerated the presence of oxygen in the gas phase up to 3 % (v/v). 27983475 8 15 dep % 907:907 arg1 v/v 910:912 v/v 910:912 v/v 910:912 Strain KRT did not need the presence of a reducing agent in the medium and tolerated the presence of oxygen in the gas phase up to 3 % (v/v). 27983475 8 16 theme gas 889:891 arg1 phase 893:897 the gas phase 885:897 the gas phase up to 3 % (v/v) 885:913 Strain KRT did not need the presence of a reducing agent in the medium and tolerated the presence of oxygen in the gas phase up to 3 % (v/v). 27983475 1 17 theme novel 45:49 arg1 representative 51:64 a novel representative 43:64 a novel representative of the phylum Calditrichaeota 43:94 nov., a novel representative of the phylum Calditrichaeota. 27983475 1 17 theme novel 45:49 arg1 nov. 37:40 nov. 37:40 nov. 37:40 nov., a novel representative of the phylum Calditrichaeota. 27983475 8 18 dep 3  905:906 arg1 to 902:903 to 902:903 to 902:903 Strain KRT did not need the presence of a reducing agent in the medium and tolerated the presence of oxygen in the gas phase up to 3 % (v/v). 27983475 13 19 theme phylum 1286:1291 arg1 Calditrichaeota 1293:1307 the phylum Calditrichaeota 1282:1307 the phylum Calditrichaeota where it represented a novel species of a new genus, for which the name Calorithrix insularis gen. nov., sp 1282:1415 16S rRNA gene sequence analysis placed isolate KRT in the phylum Calditrichaeota where it represented a novel species of a new genus, for which the name Calorithrix insularis gen. nov., sp. 27983475 15 20 theme insularis 1467:1475 arg1 strain 1445:1450 The type strain 1436:1450 The type strain of Calorithrix insularis 1436:1475 The type strain of Calorithrix insularis is KRT (=DSM 101605T=VKM B-3022T). 27983475 15 20 theme insularis 1467:1475 arg1 KRT 1480:1482 KRT 1480:1482 KRT (=DSM 101605T=VKM B-3022T) 1480:1509 The type strain of Calorithrix insularis is KRT (=DSM 101605T=VKM B-3022T). 27983475 4 21 theme % 435:435 arg1 NaCl 443:446 1-3 % (w/v) NaCl 431:446 1-3 % (w/v) NaCl 431:446 Optimal growth conditions were pH 6.6, 55 °C and 1-3 % (w/v) NaCl. 27983475 5 22 theme wide 482:485 arg1 range 487:491 a wide range 480:491 a wide range of proteinaceous substrates 480:519 Strain KRT was able to ferment a wide range of proteinaceous substrates, pyruvate, and mono-, di- and polysaccharides. 27983475 13 23 theme gen. 1403:1406 arg1 nov. 1408:1411 the name Calorithrix insularis gen. nov. 1372:1411 the name Calorithrix insularis gen. nov. 1372:1411 16S rRNA gene sequence analysis placed isolate KRT in the phylum Calditrichaeota where it represented a novel species of a new genus, for which the name Calorithrix insularis gen. nov., sp. 27983475 2 24 dep Kunashir 232:239 arg1 Island 241:246 Island 241:246 Kunashir Island 232:246 A moderately thermophilic, anaerobic bacterium designated as strain KRT was isolated from a shallow-water submarine hydrothermal vent (Kunashir Island, Southern Kurils, Russia). 27983475 0 25 theme insularis 12:20 arg1 nov. 27:30 Calorithrix insularis gen. nov. 0:30 Calorithrix insularis gen. nov. 0:30 Calorithrix insularis gen. nov., sp. 27983475 4 26 theme 1-3  431:434 arg1 % 435:435 % 435:435 % 435:435 Optimal growth conditions were pH 6.6, 55 °C and 1-3 % (w/v) NaCl. 27983475 7 27 theme main 739:742 arg1 ammonium 720:727 ammonium 720:727 ammonium 720:727 Nitrate significantly stimulated the growth on proteinaceous substrates decreasing H2 formation, ammonium being the main product of nitrate reduction. 27983475 7 27 theme main 739:742 arg1 product 744:750 the main product 735:750 the main product of nitrate reduction 735:771 Nitrate significantly stimulated the growth on proteinaceous substrates decreasing H2 formation, ammonium being the main product of nitrate reduction. 27983475 8 28 theme agent 825:829 arg1 presence 802:809 the presence 798:809 the presence of a reducing agent in the medium 798:843 Strain KRT did not need the presence of a reducing agent in the medium and tolerated the presence of oxygen in the gas phase up to 3 % (v/v). 27983475 6 29 theme proteinaceous 598:610 arg1 compounds 612:620 proteinaceous compounds 598:620 proteinaceous compounds 598:620 The best growth occurred with proteinaceous compounds. 27983475 2 30 attach isolated 173:180 arg1 vent 226:229 a shallow-water submarine hydrothermal vent 187:229 a shallow-water submarine hydrothermal vent 187:229 A moderately thermophilic, anaerobic bacterium designated as strain KRT was isolated from a shallow-water submarine hydrothermal vent (Kunashir Island, Southern Kurils, Russia). 27983475 2 30 attach isolated 173:180 arg2 bacterium 134:142 A moderately thermophilic, anaerobic bacterium 97:142 A moderately thermophilic, anaerobic bacterium designated as strain KRT 97:167 A moderately thermophilic, anaerobic bacterium designated as strain KRT was isolated from a shallow-water submarine hydrothermal vent (Kunashir Island, Southern Kurils, Russia). 27983475 0 31 theme Calorithrix 0:10 arg1 nov. 27:30 Calorithrix insularis gen. nov. 0:30 Calorithrix insularis gen. nov. 0:30 Calorithrix insularis gen. nov., sp. 27983475 4 32 dep % 435:435 arg1 w/v 438:440 w/v 438:440 w/v 438:440 Optimal growth conditions were pH 6.6, 55 °C and 1-3 % (w/v) NaCl. 27983475 4 33 theme Optimal 382:388 arg1 conditions 397:406 Optimal growth conditions 382:406 Optimal growth conditions 382:406 Optimal growth conditions were pH 6.6, 55 °C and 1-3 % (w/v) NaCl. 27983475 7 34 theme reduction 763:771 arg1 ammonium 720:727 ammonium 720:727 ammonium 720:727 Nitrate significantly stimulated the growth on proteinaceous substrates decreasing H2 formation, ammonium being the main product of nitrate reduction. 27983475 7 34 theme reduction 763:771 arg1 product 744:750 the main product 735:750 the main product of nitrate reduction 735:771 Nitrate significantly stimulated the growth on proteinaceous substrates decreasing H2 formation, ammonium being the main product of nitrate reduction. 27983475 5 35 theme proteinaceous 496:508 arg1 substrates 510:519 proteinaceous substrates 496:519 proteinaceous substrates 496:519 Strain KRT was able to ferment a wide range of proteinaceous substrates, pyruvate, and mono-, di- and polysaccharides. 27983475 1 36 theme phylum 73:78 arg1 Calditrichaeota 80:94 the phylum Calditrichaeota 69:94 the phylum Calditrichaeota 69:94 nov., a novel representative of the phylum Calditrichaeota. 27983475 9 37 theme KRT 969:971 arg1 aerotolerance 944:956 aerotolerance 944:956 aerotolerance of isolate KRT 944:971 In the presence of nitrate, aerotolerance of isolate KRT was enhanced up to 6-8 % O2 (v/v). 27983475 13 38 theme isolate 1267:1273 arg1 KRT 1275:1277 isolate KRT 1267:1277 isolate KRT 1267:1277 16S rRNA gene sequence analysis placed isolate KRT in the phylum Calditrichaeota where it represented a novel species of a new genus, for which the name Calorithrix insularis gen. nov., sp. 27983475 0 39 theme gen. 22:25 arg1 nov. 27:30 Calorithrix insularis gen. nov. 0:30 Calorithrix insularis gen. nov. 0:30 Calorithrix insularis gen. nov., sp. 27983475 12 40 theme 47.3 mol 1217:1224 arg1 % 1225:1225 47.3 mol% 1217:1225 47.3 mol% 1217:1225 The G+C content of the genomic DNA of strain KRT was 47.3 mol%. 27983475 12 40 theme 47.3 mol 1217:1224 arg1 content 1172:1178 The G+C content 1164:1178 The G+C content of the genomic DNA of strain KRT 1164:1211 The G+C content of the genomic DNA of strain KRT was 47.3 mol%. 27983475 1 41 theme Calditrichaeota 80:94 arg1 representative 51:64 a novel representative 43:64 a novel representative of the phylum Calditrichaeota 43:94 nov., a novel representative of the phylum Calditrichaeota. 27983475 1 41 theme Calditrichaeota 80:94 arg1 nov. 37:40 nov. 37:40 nov. 37:40 nov., a novel representative of the phylum Calditrichaeota. 27983475 15 42 theme =DSM 1485:1488 arg1 B-3022T 1502:1508 =DSM 101605T=VKM B-3022T 1485:1508 =DSM 101605T=VKM B-3022T 1485:1508 The type strain of Calorithrix insularis is KRT (=DSM 101605T=VKM B-3022T). 27983475 15 42 theme =DSM 1485:1488 arg1 KRT 1480:1482 KRT 1480:1482 KRT (=DSM 101605T=VKM B-3022T) 1480:1509 The type strain of Calorithrix insularis is KRT (=DSM 101605T=VKM B-3022T). 27983475 8 43 theme reducing 816:823 arg1 agent 825:829 a reducing agent 814:829 a reducing agent 814:829 Strain KRT did not need the presence of a reducing agent in the medium and tolerated the presence of oxygen in the gas phase up to 3 % (v/v). 27983475 3 44 theme variable 365:372 arg1 length 374:379 variable length 365:379 variable length 365:379 Cells of strain KRT were thin (0.2-0.3 µm), flexible, motile, Gram-stain-negative rods of variable length. 27983475 9 45 dep % 996:996 arg1 up 986:987 up 986:987 up 986:987 In the presence of nitrate, aerotolerance of isolate KRT was enhanced up to 6-8 % O2 (v/v). 27983475 3 46 dep thin 300:303 arg1 Gram-stain-negative 337:355 Gram-stain-negative 337:355 Gram-stain-negative 337:355 Cells of strain KRT were thin (0.2-0.3 µm), flexible, motile, Gram-stain-negative rods of variable length. 27983475 3 46 dep thin 300:303 arg1 motile 329:334 motile 329:334 motile 329:334 Cells of strain KRT were thin (0.2-0.3 µm), flexible, motile, Gram-stain-negative rods of variable length. 27983475 3 46 dep thin 300:303 arg1 0.2-0.3 µm 306:315 0.2-0.3 µm 306:315 0.2-0.3 µm 306:315 Cells of strain KRT were thin (0.2-0.3 µm), flexible, motile, Gram-stain-negative rods of variable length. 27983475 3 46 dep thin 300:303 arg1 flexible 319:326 flexible 319:326 flexible 319:326 Cells of strain KRT were thin (0.2-0.3 µm), flexible, motile, Gram-stain-negative rods of variable length. 27983475 13 47 theme new 1351:1353 arg1 genus 1355:1359 a new genus 1349:1359 a new genus 1349:1359 16S rRNA gene sequence analysis placed isolate KRT in the phylum Calditrichaeota where it represented a novel species of a new genus, for which the name Calorithrix insularis gen. nov., sp. 27983475 12 48 theme G+C 1168:1170 arg1 % 1225:1225 47.3 mol% 1217:1225 47.3 mol% 1217:1225 The G+C content of the genomic DNA of strain KRT was 47.3 mol%. 27983475 12 48 theme G+C 1168:1170 arg1 content 1172:1178 The G+C content 1164:1178 The G+C content of the genomic DNA of strain KRT 1164:1211 The G+C content of the genomic DNA of strain KRT was 47.3 mol%. 27983475 6 49 theme best 572:575 arg1 growth 577:582 The best growth 568:582 The best growth 568:582 The best growth occurred with proteinaceous compounds. 27983475 8 50 from presence 863:870 arg1 phase 893:897 the gas phase 885:897 the gas phase up to 3 % (v/v) 885:913 Strain KRT did not need the presence of a reducing agent in the medium and tolerated the presence of oxygen in the gas phase up to 3 % (v/v). 27983475 3 51 theme length 374:379 arg1 rods 357:360 thin (0.2-0.3 µm), flexible, motile, Gram-stain-negative rods 300:360 thin (0.2-0.3 µm), flexible, motile, Gram-stain-negative rods of variable length 300:379 Cells of strain KRT were thin (0.2-0.3 µm), flexible, motile, Gram-stain-negative rods of variable length. 27983475 7 52 from growth 660:665 arg1 substrates 684:693 proteinaceous substrates 670:693 proteinaceous substrates 670:693 Nitrate significantly stimulated the growth on proteinaceous substrates decreasing H2 formation, ammonium being the main product of nitrate reduction. 27983475 2 53 theme strain 158:163 arg1 KRT 165:167 strain KRT 158:167 strain KRT 158:167 A moderately thermophilic, anaerobic bacterium designated as strain KRT was isolated from a shallow-water submarine hydrothermal vent (Kunashir Island, Southern Kurils, Russia). 27983475 8 54 from presence 802:809 arg1 medium 838:843 the medium 834:843 the medium 834:843 Strain KRT did not need the presence of a reducing agent in the medium and tolerated the presence of oxygen in the gas phase up to 3 % (v/v). 27983475 13 55 theme insularis 1393:1401 arg1 nov. 1408:1411 the name Calorithrix insularis gen. nov. 1372:1411 the name Calorithrix insularis gen. nov. 1372:1411 16S rRNA gene sequence analysis placed isolate KRT in the phylum Calditrichaeota where it represented a novel species of a new genus, for which the name Calorithrix insularis gen. nov., sp. 27983475 8 56 attach presence 863:870 arg2 oxygen 875:880 oxygen 875:880 oxygen 875:880 Strain KRT did not need the presence of a reducing agent in the medium and tolerated the presence of oxygen in the gas phase up to 3 % (v/v). 27983475 8 56 attach presence 863:870 arg1 phase 893:897 the gas phase 885:897 the gas phase up to 3 % (v/v) 885:913 Strain KRT did not need the presence of a reducing agent in the medium and tolerated the presence of oxygen in the gas phase up to 3 % (v/v). 27983475 2 57 theme hydrothermal 213:224 arg1 vent 226:229 a shallow-water submarine hydrothermal vent 187:229 a shallow-water submarine hydrothermal vent 187:229 A moderately thermophilic, anaerobic bacterium designated as strain KRT was isolated from a shallow-water submarine hydrothermal vent (Kunashir Island, Southern Kurils, Russia). 27983475 13 58 theme gene 1237:1240 arg1 analysis 1251:1258 16S rRNA gene sequence analysis 1228:1258 16S rRNA gene sequence analysis 1228:1258 16S rRNA gene sequence analysis placed isolate KRT in the phylum Calditrichaeota where it represented a novel species of a new genus, for which the name Calorithrix insularis gen. nov., sp. 27983475 2 59 dep thermophilic 110:121 arg1 anaerobic 124:132 anaerobic 124:132 anaerobic 124:132 A moderately thermophilic, anaerobic bacterium designated as strain KRT was isolated from a shallow-water submarine hydrothermal vent (Kunashir Island, Southern Kurils, Russia). 27983475 3 60 theme strain 284:289 arg1 KRT 291:293 strain KRT 284:293 strain KRT 284:293 Cells of strain KRT were thin (0.2-0.3 µm), flexible, motile, Gram-stain-negative rods of variable length. 27983475 2 61 theme shallow-water 189:201 arg1 vent 226:229 a shallow-water submarine hydrothermal vent 187:229 a shallow-water submarine hydrothermal vent 187:229 A moderately thermophilic, anaerobic bacterium designated as strain KRT was isolated from a shallow-water submarine hydrothermal vent (Kunashir Island, Southern Kurils, Russia). 27983475 2 62 theme submarine 203:211 arg1 vent 226:229 a shallow-water submarine hydrothermal vent 187:229 a shallow-water submarine hydrothermal vent 187:229 A moderately thermophilic, anaerobic bacterium designated as strain KRT was isolated from a shallow-water submarine hydrothermal vent (Kunashir Island, Southern Kurils, Russia). 27983475 9 63 dep nitrate 935:941 arg1 the 919:921 the 919:921 the 919:921 In the presence of nitrate, aerotolerance of isolate KRT was enhanced up to 6-8 % O2 (v/v). 27983475 9 63 dep nitrate 935:941 arg1 presence 923:930 presence 923:930 presence 923:930 In the presence of nitrate, aerotolerance of isolate KRT was enhanced up to 6-8 % O2 (v/v). 27983475 13 64 theme sequence 1242:1249 arg1 analysis 1251:1258 16S rRNA gene sequence analysis 1228:1258 16S rRNA gene sequence analysis 1228:1258 16S rRNA gene sequence analysis placed isolate KRT in the phylum Calditrichaeota where it represented a novel species of a new genus, for which the name Calorithrix insularis gen. nov., sp. 27983475 15 65 theme type 1440:1443 arg1 strain 1445:1450 The type strain 1436:1450 The type strain of Calorithrix insularis 1436:1475 The type strain of Calorithrix insularis is KRT (=DSM 101605T=VKM B-3022T). 27983475 15 65 theme type 1440:1443 arg1 KRT 1480:1482 KRT 1480:1482 KRT (=DSM 101605T=VKM B-3022T) 1480:1509 The type strain of Calorithrix insularis is KRT (=DSM 101605T=VKM B-3022T). 27983475 9 66 theme isolate 961:967 arg1 KRT 969:971 isolate KRT 961:971 isolate KRT 961:971 In the presence of nitrate, aerotolerance of isolate KRT was enhanced up to 6-8 % O2 (v/v). 27983475 7 67 theme H2 706:707 arg1 formation 709:717 H2 formation 706:717 H2 formation 706:717 Nitrate significantly stimulated the growth on proteinaceous substrates decreasing H2 formation, ammonium being the main product of nitrate reduction. 27983475 8 68 theme oxygen 875:880 arg1 presence 863:870 the presence 859:870 the presence of oxygen in the gas phase up to 3 % (v/v) 859:913 Strain KRT did not need the presence of a reducing agent in the medium and tolerated the presence of oxygen in the gas phase up to 3 % (v/v). 27983475 13 69 theme genus 1355:1359 arg1 species 1338:1344 a novel species 1330:1344 a novel species of a new genus, for which the name Calorithrix insularis gen. nov., sp 1330:1415 16S rRNA gene sequence analysis placed isolate KRT in the phylum Calditrichaeota where it represented a novel species of a new genus, for which the name Calorithrix insularis gen. nov., sp. 27983475 13 70 theme name 1376:1379 arg1 nov. 1408:1411 the name Calorithrix insularis gen. nov. 1372:1411 the name Calorithrix insularis gen. nov. 1372:1411 16S rRNA gene sequence analysis placed isolate KRT in the phylum Calditrichaeota where it represented a novel species of a new genus, for which the name Calorithrix insularis gen. nov., sp. 27983475 2 71 dep isolated 173:180 arg1 Russia 266:271 Russia 266:271 Russia 266:271 A moderately thermophilic, anaerobic bacterium designated as strain KRT was isolated from a shallow-water submarine hydrothermal vent (Kunashir Island, Southern Kurils, Russia). 27983475 2 71 dep isolated 173:180 arg1 Kurils 258:263 Kurils 258:263 Kurils 258:263 A moderately thermophilic, anaerobic bacterium designated as strain KRT was isolated from a shallow-water submarine hydrothermal vent (Kunashir Island, Southern Kurils, Russia). 27983475 2 71 dep isolated 173:180 arg1 Kunashir 232:239 Kunashir 232:239 Kunashir 232:239 A moderately thermophilic, anaerobic bacterium designated as strain KRT was isolated from a shallow-water submarine hydrothermal vent (Kunashir Island, Southern Kurils, Russia). 27983475 3 72 theme thin 300:303 arg1 rods 357:360 thin (0.2-0.3 µm), flexible, motile, Gram-stain-negative rods 300:360 thin (0.2-0.3 µm), flexible, motile, Gram-stain-negative rods of variable length 300:379 Cells of strain KRT were thin (0.2-0.3 µm), flexible, motile, Gram-stain-negative rods of variable length. 27983475 4 73 theme growth 390:395 arg1 conditions 397:406 Optimal growth conditions 382:406 Optimal growth conditions 382:406 Optimal growth conditions were pH 6.6, 55 °C and 1-3 % (w/v) NaCl. 27983475 13 74 theme novel 1332:1336 arg1 species 1338:1344 a novel species 1330:1344 a novel species of a new genus, for which the name Calorithrix insularis gen. nov., sp 1330:1415 16S rRNA gene sequence analysis placed isolate KRT in the phylum Calditrichaeota where it represented a novel species of a new genus, for which the name Calorithrix insularis gen. nov., sp. 27983475 5 75 theme Strain 449:454 arg1 KRT 456:458 Strain KRT 449:458 Strain KRT 449:458 Strain KRT was able to ferment a wide range of proteinaceous substrates, pyruvate, and mono-, di- and polysaccharides. 27983475 8 76 dep phase 893:897 arg1 % 907:907 % 907:907 % 907:907 Strain KRT did not need the presence of a reducing agent in the medium and tolerated the presence of oxygen in the gas phase up to 3 % (v/v). 27983475 10 77 theme Strain 1008:1013 arg1 KRT 1015:1017 Strain KRT 1008:1017 Strain KRT 1008:1017 Strain KRT was able to grow chemolithoheterotrophically, oxidizing H2 and reducing nitrate to ammonium. 27983475 2 78 theme thermophilic 110:121 arg1 bacterium 134:142 A moderately thermophilic, anaerobic bacterium 97:142 A moderately thermophilic, anaerobic bacterium designated as strain KRT 97:167 A moderately thermophilic, anaerobic bacterium designated as strain KRT was isolated from a shallow-water submarine hydrothermal vent (Kunashir Island, Southern Kurils, Russia). 27983475 7 79 theme nitrate 755:761 arg1 reduction 763:771 nitrate reduction 755:771 nitrate reduction 755:771 Nitrate significantly stimulated the growth on proteinaceous substrates decreasing H2 formation, ammonium being the main product of nitrate reduction. 27983475 15 80 theme 101605T=VKM 1490:1500 arg1 B-3022T 1502:1508 =DSM 101605T=VKM B-3022T 1485:1508 =DSM 101605T=VKM B-3022T 1485:1508 The type strain of Calorithrix insularis is KRT (=DSM 101605T=VKM B-3022T). 27983475 15 80 theme 101605T=VKM 1490:1500 arg1 KRT 1480:1482 KRT 1480:1482 KRT (=DSM 101605T=VKM B-3022T) 1480:1509 The type strain of Calorithrix insularis is KRT (=DSM 101605T=VKM B-3022T). 27983475 7 81 theme proteinaceous 670:682 arg1 substrates 684:693 proteinaceous substrates 670:693 proteinaceous substrates 670:693 Nitrate significantly stimulated the growth on proteinaceous substrates decreasing H2 formation, ammonium being the main product of nitrate reduction. 25191062 9 0 theme novel 1582:1586 arg1 hierarchy 1618:1626 a novel S. mutans serotype prevalence hierarchy 1580:1626 a novel S. mutans serotype prevalence hierarchy in children from this region 1580:1655 CONCLUSION The present data clearly establishes a novel S. mutans serotype prevalence hierarchy in children from this region, compared with those that have been reported elsewhere. 25191062 8 1 theme positive 1413:1420 arg1 samples 1422:1428 the S. mutans positive samples 1399:1428 the S. mutans positive samples in both groups 1399:1443 Further analysis of the S. mutans positive samples in both groups indicated a higher prevalence of serotype k and e, followed by serotype f in CA group. 25191062 1 2 theme caries 237:242 arg1 development 215:225 The development 211:225 The development of dental caries 211:242 BACKGROUND The development of dental caries has been associated with the oral prevalence of Streptococcus mutans. 25191062 2 3 theme 16s 539:541 arg1 rRNA 543:546 16s rRNA 539:546 16s rRNA homology 539:555 Four serotypes of S. mutans have been reported, namely serotype c, e, f, and k that are classified based on the composition and linkages of cell wall polysaccharides, response to physiological reactions, sero-specificity and 16s rRNA homology. 25191062 9 4 theme mutans 1591:1596 arg1 hierarchy 1618:1626 a novel S. mutans serotype prevalence hierarchy 1580:1626 a novel S. mutans serotype prevalence hierarchy in children from this region 1580:1655 CONCLUSION The present data clearly establishes a novel S. mutans serotype prevalence hierarchy in children from this region, compared with those that have been reported elsewhere. 25191062 10 5 theme serotype 1784:1791 arg1 k 1793:1793 serotype k 1784:1793 serotype k 1784:1793 Besides, the data are also clinically significant as the occurrence of serotype k has been associated with infective endocarditis. 25191062 9 6 theme prevalence 1607:1616 arg1 hierarchy 1618:1626 a novel S. mutans serotype prevalence hierarchy 1580:1626 a novel S. mutans serotype prevalence hierarchy in children from this region 1580:1655 CONCLUSION The present data clearly establishes a novel S. mutans serotype prevalence hierarchy in children from this region, compared with those that have been reported elsewhere. 25191062 5 7 theme groups 996:1001 arg1 saliva 946:951 whole saliva 940:951 whole saliva of caries active (CA) and caries free (CF) groups 940:1001 MATERIALS AND METHODS Genomic DNA isolated from whole saliva of caries active (CA) and caries free (CF) groups were first screened for the presence of S. mutans by strain specific polymerase chain reaction (PCR). 25191062 0 8 theme India 193:197 arg1 region 183:188 the Southern region 170:188 the Southern region of India 170:197 Serotype specific polymerase chain reaction identifies a higher prevalence of streptococcus mutans serotype k and e in a random group of children with dental caries from the Southern region of India. 25191062 10 9 theme infective 1820:1828 arg1 endocarditis 1830:1841 infective endocarditis 1820:1841 infective endocarditis 1820:1841 Besides, the data are also clinically significant as the occurrence of serotype k has been associated with infective endocarditis. 25191062 3 10 theme serotypes 697:705 arg1 prevalence 667:676 the prevalence 663:676 the prevalence of the other three serotypes, e, f, and k 663:718 Although the oral prevalence of S. mutans serotype c in Indian subjects with or without caries is known, the prevalence of the other three serotypes, e, f, and k are not known. 25191062 0 11 theme random 121:126 arg1 children 137:144 children 137:144 children with dental caries from the Southern region of India 137:197 Serotype specific polymerase chain reaction identifies a higher prevalence of streptococcus mutans serotype k and e in a random group of children with dental caries from the Southern region of India. 25191062 0 11 theme random 121:126 arg1 group 128:132 a random group 119:132 a random group of children with dental caries from the Southern region of India 119:197 Serotype specific polymerase chain reaction identifies a higher prevalence of streptococcus mutans serotype k and e in a random group of children with dental caries from the Southern region of India. 25191062 5 12 theme Genomic 914:920 arg1 DNA 922:924 Genomic DNA 914:924 Genomic DNA 914:924 MATERIALS AND METHODS Genomic DNA isolated from whole saliva of caries active (CA) and caries free (CF) groups were first screened for the presence of S. mutans by strain specific polymerase chain reaction (PCR). 25191062 8 13 theme serotype 1478:1485 arg1 k 1487:1487 serotype k 1478:1487 serotype k 1478:1487 Further analysis of the S. mutans positive samples in both groups indicated a higher prevalence of serotype k and e, followed by serotype f in CA group. 25191062 0 14 from prevalence 64:73 arg1 children 137:144 children 137:144 children with dental caries from the Southern region of India 137:197 Serotype specific polymerase chain reaction identifies a higher prevalence of streptococcus mutans serotype k and e in a random group of children with dental caries from the Southern region of India. 25191062 0 14 from prevalence 64:73 arg1 group 128:132 a random group 119:132 a random group of children with dental caries from the Southern region of India 119:197 Serotype specific polymerase chain reaction identifies a higher prevalence of streptococcus mutans serotype k and e in a random group of children with dental caries from the Southern region of India. 25191062 3 15 theme other 685:689 arg1 f 711:711 f 711:711 f 711:711 Although the oral prevalence of S. mutans serotype c in Indian subjects with or without caries is known, the prevalence of the other three serotypes, e, f, and k are not known. 25191062 3 15 theme other 685:689 arg1 k 718:718 k 718:718 k 718:718 Although the oral prevalence of S. mutans serotype c in Indian subjects with or without caries is known, the prevalence of the other three serotypes, e, f, and k are not known. 25191062 3 15 theme other 685:689 arg1 e 708:708 e 708:708 e 708:708 Although the oral prevalence of S. mutans serotype c in Indian subjects with or without caries is known, the prevalence of the other three serotypes, e, f, and k are not known. 25191062 3 15 theme other 685:689 arg1 serotypes 697:705 the other three serotypes 681:705 the other three serotypes 681:705 Although the oral prevalence of S. mutans serotype c in Indian subjects with or without caries is known, the prevalence of the other three serotypes, e, f, and k are not known. 25191062 4 16 from occurrence 781:790 arg1 children 824:831 children 824:831 children with or without caries within the age group of 6-12 years 824:889 Hence in this study, we have investigated the occurrence of the e, f, and k serotypes in children with or without caries within the age group of 6-12 years. 25191062 9 17 from hierarchy 1618:1626 arg1 children 1631:1638 children 1631:1638 children from this region 1631:1655 CONCLUSION The present data clearly establishes a novel S. mutans serotype prevalence hierarchy in children from this region, compared with those that have been reported elsewhere. 25191062 9 17 from hierarchy 1618:1626 arg1 region 1650:1655 this region 1645:1655 this region 1645:1655 CONCLUSION The present data clearly establishes a novel S. mutans serotype prevalence hierarchy in children from this region, compared with those that have been reported elsewhere. 25191062 8 18 from f 1517:1517 arg1 group 1525:1529 CA group 1522:1529 CA group 1522:1529 Further analysis of the S. mutans positive samples in both groups indicated a higher prevalence of serotype k and e, followed by serotype f in CA group. 25191062 5 19 theme polymerase 1072:1081 arg1 PCR 1099:1101 PCR 1099:1101 PCR 1099:1101 MATERIALS AND METHODS Genomic DNA isolated from whole saliva of caries active (CA) and caries free (CF) groups were first screened for the presence of S. mutans by strain specific polymerase chain reaction (PCR). 25191062 5 19 theme polymerase 1072:1081 arg1 reaction 1089:1096 strain specific polymerase chain reaction 1056:1096 strain specific polymerase chain reaction (PCR) 1056:1102 MATERIALS AND METHODS Genomic DNA isolated from whole saliva of caries active (CA) and caries free (CF) groups were first screened for the presence of S. mutans by strain specific polymerase chain reaction (PCR). 25191062 3 20 theme oral 571:574 arg1 prevalence 576:585 the oral prevalence 567:585 the oral prevalence of S. mutans serotype c in Indian subjects with or without caries 567:651 Although the oral prevalence of S. mutans serotype c in Indian subjects with or without caries is known, the prevalence of the other three serotypes, e, f, and k are not known. 25191062 6 21 theme mutans 1163:1168 arg1 presence 1148:1155 the presence 1144:1155 the presence of S. mutans 1144:1168 Those samples that tested positive for the presence of S. mutans were further analyzed by serotype specific PCR to identify the prevalence of the serotypes. 25191062 6 22 theme specific 1204:1211 arg1 PCR 1213:1215 serotype specific PCR 1195:1215 serotype specific PCR 1195:1215 Those samples that tested positive for the presence of S. mutans were further analyzed by serotype specific PCR to identify the prevalence of the serotypes. 25191062 7 23 dep RESULTS 1262:1268 arg1 indicated 1290:1298 indicated 1290:1298 indicated a higher prevalence of S. mutans in CA group (80%) relative to CF group (43%) 1290:1376 RESULTS Strain specific PCR indicated a higher prevalence of S. mutans in CA group (80%) relative to CF group (43%). 25191062 5 24 theme mutans 1046:1051 arg1 presence 1031:1038 the presence 1027:1038 the presence of S. mutans 1027:1051 MATERIALS AND METHODS Genomic DNA isolated from whole saliva of caries active (CA) and caries free (CF) groups were first screened for the presence of S. mutans by strain specific polymerase chain reaction (PCR). 25191062 5 25 theme active 963:968 arg1 caries 956:961 caries 956:961 caries active (CA) 956:973 MATERIALS AND METHODS Genomic DNA isolated from whole saliva of caries active (CA) and caries free (CF) groups were first screened for the presence of S. mutans by strain specific polymerase chain reaction (PCR). 25191062 2 26 theme wall 459:462 arg1 response 481:488 response 481:488 response to physiological reactions 481:515 Four serotypes of S. mutans have been reported, namely serotype c, e, f, and k that are classified based on the composition and linkages of cell wall polysaccharides, response to physiological reactions, sero-specificity and 16s rRNA homology. 25191062 2 26 theme wall 459:462 arg1 polysaccharides 464:478 cell wall polysaccharides 454:478 cell wall polysaccharides 454:478 Four serotypes of S. mutans have been reported, namely serotype c, e, f, and k that are classified based on the composition and linkages of cell wall polysaccharides, response to physiological reactions, sero-specificity and 16s rRNA homology. 25191062 2 26 theme wall 459:462 arg1 homology 548:555 16s rRNA homology 539:555 16s rRNA homology 539:555 Four serotypes of S. mutans have been reported, namely serotype c, e, f, and k that are classified based on the composition and linkages of cell wall polysaccharides, response to physiological reactions, sero-specificity and 16s rRNA homology. 25191062 2 26 theme wall 459:462 arg1 sero-specificity 518:533 sero-specificity 518:533 sero-specificity 518:533 Four serotypes of S. mutans have been reported, namely serotype c, e, f, and k that are classified based on the composition and linkages of cell wall polysaccharides, response to physiological reactions, sero-specificity and 16s rRNA homology. 25191062 5 27 theme strain 1056:1061 arg1 PCR 1099:1101 PCR 1099:1101 PCR 1099:1101 MATERIALS AND METHODS Genomic DNA isolated from whole saliva of caries active (CA) and caries free (CF) groups were first screened for the presence of S. mutans by strain specific polymerase chain reaction (PCR). 25191062 5 27 theme strain 1056:1061 arg1 reaction 1089:1096 strain specific polymerase chain reaction 1056:1096 strain specific polymerase chain reaction (PCR) 1056:1102 MATERIALS AND METHODS Genomic DNA isolated from whole saliva of caries active (CA) and caries free (CF) groups were first screened for the presence of S. mutans by strain specific polymerase chain reaction (PCR). 25191062 0 28 theme serotype 99:106 arg1 k 108:108 serotype k 99:108 serotype k 99:108 Serotype specific polymerase chain reaction identifies a higher prevalence of streptococcus mutans serotype k and e in a random group of children with dental caries from the Southern region of India. 25191062 8 29 theme CA 1522:1523 arg1 group 1525:1529 CA group 1522:1529 CA group 1522:1529 Further analysis of the S. mutans positive samples in both groups indicated a higher prevalence of serotype k and e, followed by serotype f in CA group. 25191062 4 30 theme k 809:809 arg1 serotypes 811:819 the e, f, and k serotypes 795:819 the e, f, and k serotypes 795:819 Hence in this study, we have investigated the occurrence of the e, f, and k serotypes in children with or without caries within the age group of 6-12 years. 25191062 2 31 theme serotype 369:376 arg1 c 378:378 serotype c 369:378 serotype c 369:378 Four serotypes of S. mutans have been reported, namely serotype c, e, f, and k that are classified based on the composition and linkages of cell wall polysaccharides, response to physiological reactions, sero-specificity and 16s rRNA homology. 25191062 5 32 theme whole 940:944 arg1 saliva 946:951 whole saliva 940:951 whole saliva of caries active (CA) and caries free (CF) groups 940:1001 MATERIALS AND METHODS Genomic DNA isolated from whole saliva of caries active (CA) and caries free (CF) groups were first screened for the presence of S. mutans by strain specific polymerase chain reaction (PCR). 25191062 4 33 theme age 867:869 arg1 group 871:875 the age group 863:875 the age group of 6-12 years 863:889 Hence in this study, we have investigated the occurrence of the e, f, and k serotypes in children with or without caries within the age group of 6-12 years. 25191062 4 33 theme age 867:869 arg1 years 885:889 6-12 years 880:889 6-12 years 880:889 Hence in this study, we have investigated the occurrence of the e, f, and k serotypes in children with or without caries within the age group of 6-12 years. 25191062 0 34 theme Serotype 0:7 arg1 reaction 35:42 Serotype specific polymerase chain reaction 0:42 Serotype specific polymerase chain reaction 0:42 Serotype specific polymerase chain reaction identifies a higher prevalence of streptococcus mutans serotype k and e in a random group of children with dental caries from the Southern region of India. 25191062 5 35 theme free 986:989 arg1 groups 996:1001 caries free (CF) groups 979:1001 caries free (CF) groups 979:1001 MATERIALS AND METHODS Genomic DNA isolated from whole saliva of caries active (CA) and caries free (CF) groups were first screened for the presence of S. mutans by strain specific polymerase chain reaction (PCR). 25191062 0 36 theme polymerase 18:27 arg1 reaction 35:42 Serotype specific polymerase chain reaction 0:42 Serotype specific polymerase chain reaction 0:42 Serotype specific polymerase chain reaction identifies a higher prevalence of streptococcus mutans serotype k and e in a random group of children with dental caries from the Southern region of India. 25191062 5 37 theme CF 992:993 arg1 groups 996:1001 caries free (CF) groups 979:1001 caries free (CF) groups 979:1001 MATERIALS AND METHODS Genomic DNA isolated from whole saliva of caries active (CA) and caries free (CF) groups were first screened for the presence of S. mutans by strain specific polymerase chain reaction (PCR). 25191062 3 38 theme mutans 593:598 arg1 c 609:609 S. mutans serotype c 590:609 S. mutans serotype c 590:609 Although the oral prevalence of S. mutans serotype c in Indian subjects with or without caries is known, the prevalence of the other three serotypes, e, f, and k are not known. 25191062 8 39 from groups 1438:1443 arg1 analysis 1387:1394 Further analysis 1379:1394 Further analysis of the S. mutans positive samples in both groups 1379:1443 Further analysis of the S. mutans positive samples in both groups indicated a higher prevalence of serotype k and e, followed by serotype f in CA group. 25191062 7 40 theme higher 1302:1307 arg1 prevalence 1309:1318 a higher prevalence 1300:1318 a higher prevalence of S. mutans in CA group (80%) relative to CF group (43%) 1300:1376 RESULTS Strain specific PCR indicated a higher prevalence of S. mutans in CA group (80%) relative to CF group (43%). 25191062 1 41 theme Streptococcus 292:304 arg1 mutans 306:311 Streptococcus mutans 292:311 Streptococcus mutans 292:311 BACKGROUND The development of dental caries has been associated with the oral prevalence of Streptococcus mutans. 25191062 9 42 theme present 1547:1553 arg1 data 1555:1558 The present data 1543:1558 The present data 1543:1558 CONCLUSION The present data clearly establishes a novel S. mutans serotype prevalence hierarchy in children from this region, compared with those that have been reported elsewhere. 25191062 0 43 from region 183:188 arg1 caries 158:163 dental caries 151:163 dental caries from the Southern region of India 151:197 Serotype specific polymerase chain reaction identifies a higher prevalence of streptococcus mutans serotype k and e in a random group of children with dental caries from the Southern region of India. 25191062 3 44 theme Indian 614:619 arg1 subjects 621:628 Indian subjects 614:628 Indian subjects with or without caries 614:651 Although the oral prevalence of S. mutans serotype c in Indian subjects with or without caries is known, the prevalence of the other three serotypes, e, f, and k are not known. 25191062 2 45 dep composition 426:436 arg1 the 422:424 the 422:424 the 422:424 Four serotypes of S. mutans have been reported, namely serotype c, e, f, and k that are classified based on the composition and linkages of cell wall polysaccharides, response to physiological reactions, sero-specificity and 16s rRNA homology. 25191062 7 46 theme specific 1277:1284 arg1 PCR 1286:1288 Strain specific PCR 1270:1288 Strain specific PCR 1270:1288 RESULTS Strain specific PCR indicated a higher prevalence of S. mutans in CA group (80%) relative to CF group (43%). 25191062 3 47 theme c 609:609 arg1 prevalence 576:585 the oral prevalence 567:585 the oral prevalence of S. mutans serotype c in Indian subjects with or without caries 567:651 Although the oral prevalence of S. mutans serotype c in Indian subjects with or without caries is known, the prevalence of the other three serotypes, e, f, and k are not known. 25191062 6 48 theme serotypes 1251:1259 arg1 prevalence 1233:1242 the prevalence 1229:1242 the prevalence of the serotypes 1229:1259 Those samples that tested positive for the presence of S. mutans were further analyzed by serotype specific PCR to identify the prevalence of the serotypes. 25191062 5 49 attach isolated 926:933 arg1 saliva 946:951 whole saliva 940:951 whole saliva of caries active (CA) and caries free (CF) groups 940:1001 MATERIALS AND METHODS Genomic DNA isolated from whole saliva of caries active (CA) and caries free (CF) groups were first screened for the presence of S. mutans by strain specific polymerase chain reaction (PCR). 25191062 5 49 attach isolated 926:933 arg2 MATERIALS 892:900 MATERIALS 892:900 MATERIALS 892:900 MATERIALS AND METHODS Genomic DNA isolated from whole saliva of caries active (CA) and caries free (CF) groups were first screened for the presence of S. mutans by strain specific polymerase chain reaction (PCR). 25191062 4 50 theme years 885:889 arg1 group 871:875 the age group 863:875 the age group of 6-12 years 863:889 Hence in this study, we have investigated the occurrence of the e, f, and k serotypes in children with or without caries within the age group of 6-12 years. 25191062 4 50 theme years 885:889 arg1 years 885:889 6-12 years 880:889 6-12 years 880:889 Hence in this study, we have investigated the occurrence of the e, f, and k serotypes in children with or without caries within the age group of 6-12 years. 25191062 2 51 theme mutans 335:340 arg1 serotypes 319:327 Four serotypes 314:327 Four serotypes of S. mutans 314:340 Four serotypes of S. mutans have been reported, namely serotype c, e, f, and k that are classified based on the composition and linkages of cell wall polysaccharides, response to physiological reactions, sero-specificity and 16s rRNA homology. 25191062 1 52 theme dental 230:235 arg1 caries 237:242 dental caries 230:242 dental caries 230:242 BACKGROUND The development of dental caries has been associated with the oral prevalence of Streptococcus mutans. 25191062 2 53 theme rRNA 543:546 arg1 polysaccharides 464:478 cell wall polysaccharides 454:478 cell wall polysaccharides 454:478 Four serotypes of S. mutans have been reported, namely serotype c, e, f, and k that are classified based on the composition and linkages of cell wall polysaccharides, response to physiological reactions, sero-specificity and 16s rRNA homology. 25191062 2 53 theme rRNA 543:546 arg1 homology 548:555 16s rRNA homology 539:555 16s rRNA homology 539:555 Four serotypes of S. mutans have been reported, namely serotype c, e, f, and k that are classified based on the composition and linkages of cell wall polysaccharides, response to physiological reactions, sero-specificity and 16s rRNA homology. 25191062 9 54 theme S. 1588:1589 arg1 hierarchy 1618:1626 a novel S. mutans serotype prevalence hierarchy 1580:1626 a novel S. mutans serotype prevalence hierarchy in children from this region 1580:1655 CONCLUSION The present data clearly establishes a novel S. mutans serotype prevalence hierarchy in children from this region, compared with those that have been reported elsewhere. 25191062 5 55 dep MATERIALS 892:900 arg1 DNA 922:924 Genomic DNA 914:924 Genomic DNA 914:924 MATERIALS AND METHODS Genomic DNA isolated from whole saliva of caries active (CA) and caries free (CF) groups were first screened for the presence of S. mutans by strain specific polymerase chain reaction (PCR). 25191062 3 56 from prevalence 576:585 arg1 subjects 621:628 Indian subjects 614:628 Indian subjects with or without caries 614:651 Although the oral prevalence of S. mutans serotype c in Indian subjects with or without caries is known, the prevalence of the other three serotypes, e, f, and k are not known. 25191062 0 57 theme Southern 174:181 arg1 region 183:188 the Southern region 170:188 the Southern region of India 170:197 Serotype specific polymerase chain reaction identifies a higher prevalence of streptococcus mutans serotype k and e in a random group of children with dental caries from the Southern region of India. 25191062 8 58 theme mutans 1406:1411 arg1 samples 1422:1428 the S. mutans positive samples 1399:1428 the S. mutans positive samples in both groups 1399:1443 Further analysis of the S. mutans positive samples in both groups indicated a higher prevalence of serotype k and e, followed by serotype f in CA group. 25191062 7 59 from prevalence 1309:1318 arg1 group 1339:1343 CA group 1336:1343 CA group (80%) relative to CF group (43%) 1336:1376 RESULTS Strain specific PCR indicated a higher prevalence of S. mutans in CA group (80%) relative to CF group (43%). 25191062 7 59 from prevalence 1309:1318 arg1 % 1348:1348 80% 1346:1348 80% 1346:1348 RESULTS Strain specific PCR indicated a higher prevalence of S. mutans in CA group (80%) relative to CF group (43%). 25191062 9 60 theme serotype 1598:1605 arg1 hierarchy 1618:1626 a novel S. mutans serotype prevalence hierarchy 1580:1626 a novel S. mutans serotype prevalence hierarchy in children from this region 1580:1655 CONCLUSION The present data clearly establishes a novel S. mutans serotype prevalence hierarchy in children from this region, compared with those that have been reported elsewhere. 25191062 9 61 dep CONCLUSION 1532:1541 arg1 establishes 1568:1578 establishes 1568:1578 establishes 1568:1578 CONCLUSION The present data clearly establishes a novel S. mutans serotype prevalence hierarchy in children from this region, compared with those that have been reported elsewhere. 25191062 8 62 theme samples 1422:1428 arg1 analysis 1387:1394 Further analysis 1379:1394 Further analysis of the S. mutans positive samples in both groups 1379:1443 Further analysis of the S. mutans positive samples in both groups indicated a higher prevalence of serotype k and e, followed by serotype f in CA group. 25191062 8 63 theme higher 1457:1462 arg1 prevalence 1464:1473 a higher prevalence 1455:1473 a higher prevalence of serotype k 1455:1487 Further analysis of the S. mutans positive samples in both groups indicated a higher prevalence of serotype k and e, followed by serotype f in CA group. 25191062 7 64 theme CF 1363:1364 arg1 group 1366:1370 CF group 1363:1370 CF group (43%) 1363:1376 RESULTS Strain specific PCR indicated a higher prevalence of S. mutans in CA group (80%) relative to CF group (43%). 25191062 7 64 theme CF 1363:1364 arg1 % 1375:1375 43% 1373:1375 43% 1373:1375 RESULTS Strain specific PCR indicated a higher prevalence of S. mutans in CA group (80%) relative to CF group (43%). 25191062 4 65 theme e 799:799 arg1 serotypes 811:819 the e, f, and k serotypes 795:819 the e, f, and k serotypes 795:819 Hence in this study, we have investigated the occurrence of the e, f, and k serotypes in children with or without caries within the age group of 6-12 years. 25191062 1 66 dep BACKGROUND 200:209 arg1 associated 253:262 associated 253:262 has been associated with the oral prevalence of Streptococcus mutans 244:311 BACKGROUND The development of dental caries has been associated with the oral prevalence of Streptococcus mutans. 25191062 9 67 from region 1650:1655 arg1 hierarchy 1618:1626 a novel S. mutans serotype prevalence hierarchy 1580:1626 a novel S. mutans serotype prevalence hierarchy in children from this region 1580:1655 CONCLUSION The present data clearly establishes a novel S. mutans serotype prevalence hierarchy in children from this region, compared with those that have been reported elsewhere. 25191062 9 67 from region 1650:1655 arg1 children 1631:1638 children 1631:1638 children from this region 1631:1655 CONCLUSION The present data clearly establishes a novel S. mutans serotype prevalence hierarchy in children from this region, compared with those that have been reported elsewhere. 25191062 1 68 theme mutans 306:311 arg1 prevalence 278:287 the oral prevalence 269:287 the oral prevalence of Streptococcus mutans 269:311 BACKGROUND The development of dental caries has been associated with the oral prevalence of Streptococcus mutans. 25191062 0 69 theme children 137:144 arg1 children 137:144 children 137:144 children with dental caries from the Southern region of India 137:197 Serotype specific polymerase chain reaction identifies a higher prevalence of streptococcus mutans serotype k and e in a random group of children with dental caries from the Southern region of India. 25191062 0 69 theme children 137:144 arg1 group 128:132 a random group 119:132 a random group of children with dental caries from the Southern region of India 119:197 Serotype specific polymerase chain reaction identifies a higher prevalence of streptococcus mutans serotype k and e in a random group of children with dental caries from the Southern region of India. 25191062 7 70 theme relative 1351:1358 arg1 group 1339:1343 CA group 1336:1343 CA group (80%) relative to CF group (43%) 1336:1376 RESULTS Strain specific PCR indicated a higher prevalence of S. mutans in CA group (80%) relative to CF group (43%). 25191062 7 70 theme relative 1351:1358 arg1 % 1348:1348 80% 1346:1348 80% 1346:1348 RESULTS Strain specific PCR indicated a higher prevalence of S. mutans in CA group (80%) relative to CF group (43%). 25191062 5 71 theme specific 1063:1070 arg1 PCR 1099:1101 PCR 1099:1101 PCR 1099:1101 MATERIALS AND METHODS Genomic DNA isolated from whole saliva of caries active (CA) and caries free (CF) groups were first screened for the presence of S. mutans by strain specific polymerase chain reaction (PCR). 25191062 5 71 theme specific 1063:1070 arg1 reaction 1089:1096 strain specific polymerase chain reaction 1056:1096 strain specific polymerase chain reaction (PCR) 1056:1102 MATERIALS AND METHODS Genomic DNA isolated from whole saliva of caries active (CA) and caries free (CF) groups were first screened for the presence of S. mutans by strain specific polymerase chain reaction (PCR). 25191062 0 72 theme dental 151:156 arg1 caries 158:163 dental caries 151:163 dental caries from the Southern region of India 151:197 Serotype specific polymerase chain reaction identifies a higher prevalence of streptococcus mutans serotype k and e in a random group of children with dental caries from the Southern region of India. 25191062 8 73 theme k 1487:1487 arg1 e 1493:1493 e 1493:1493 e 1493:1493 Further analysis of the S. mutans positive samples in both groups indicated a higher prevalence of serotype k and e, followed by serotype f in CA group. 25191062 8 73 theme k 1487:1487 arg1 prevalence 1464:1473 a higher prevalence 1455:1473 a higher prevalence of serotype k 1455:1487 Further analysis of the S. mutans positive samples in both groups indicated a higher prevalence of serotype k and e, followed by serotype f in CA group. 25191062 2 74 theme physiological 493:505 arg1 reactions 507:515 physiological reactions 493:515 physiological reactions 493:515 Four serotypes of S. mutans have been reported, namely serotype c, e, f, and k that are classified based on the composition and linkages of cell wall polysaccharides, response to physiological reactions, sero-specificity and 16s rRNA homology. 25191062 5 75 theme chain 1083:1087 arg1 PCR 1099:1101 PCR 1099:1101 PCR 1099:1101 MATERIALS AND METHODS Genomic DNA isolated from whole saliva of caries active (CA) and caries free (CF) groups were first screened for the presence of S. mutans by strain specific polymerase chain reaction (PCR). 25191062 5 75 theme chain 1083:1087 arg1 reaction 1089:1096 strain specific polymerase chain reaction 1056:1096 strain specific polymerase chain reaction (PCR) 1056:1102 MATERIALS AND METHODS Genomic DNA isolated from whole saliva of caries active (CA) and caries free (CF) groups were first screened for the presence of S. mutans by strain specific polymerase chain reaction (PCR). 25191062 4 76 theme serotypes 811:819 arg1 occurrence 781:790 the occurrence 777:790 the occurrence of the e, f, and k serotypes in children with or without caries within the age group of 6-12 years 777:889 Hence in this study, we have investigated the occurrence of the e, f, and k serotypes in children with or without caries within the age group of 6-12 years. 25191062 2 77 theme cell 454:457 arg1 response 481:488 response 481:488 response to physiological reactions 481:515 Four serotypes of S. mutans have been reported, namely serotype c, e, f, and k that are classified based on the composition and linkages of cell wall polysaccharides, response to physiological reactions, sero-specificity and 16s rRNA homology. 25191062 2 77 theme cell 454:457 arg1 polysaccharides 464:478 cell wall polysaccharides 454:478 cell wall polysaccharides 454:478 Four serotypes of S. mutans have been reported, namely serotype c, e, f, and k that are classified based on the composition and linkages of cell wall polysaccharides, response to physiological reactions, sero-specificity and 16s rRNA homology. 25191062 2 77 theme cell 454:457 arg1 homology 548:555 16s rRNA homology 539:555 16s rRNA homology 539:555 Four serotypes of S. mutans have been reported, namely serotype c, e, f, and k that are classified based on the composition and linkages of cell wall polysaccharides, response to physiological reactions, sero-specificity and 16s rRNA homology. 25191062 2 77 theme cell 454:457 arg1 sero-specificity 518:533 sero-specificity 518:533 sero-specificity 518:533 Four serotypes of S. mutans have been reported, namely serotype c, e, f, and k that are classified based on the composition and linkages of cell wall polysaccharides, response to physiological reactions, sero-specificity and 16s rRNA homology. 25191062 0 78 theme mutans 92:97 arg1 prevalence 64:73 a higher prevalence 55:73 a higher prevalence of streptococcus mutans serotype k and e in a random group of children with dental caries from the Southern region of India 55:197 Serotype specific polymerase chain reaction identifies a higher prevalence of streptococcus mutans serotype k and e in a random group of children with dental caries from the Southern region of India. 25191062 5 79 theme caries 956:961 arg1 saliva 946:951 whole saliva 940:951 whole saliva of caries active (CA) and caries free (CF) groups 940:1001 MATERIALS AND METHODS Genomic DNA isolated from whole saliva of caries active (CA) and caries free (CF) groups were first screened for the presence of S. mutans by strain specific polymerase chain reaction (PCR). 25191062 7 80 theme CA 1336:1337 arg1 group 1339:1343 CA group 1336:1343 CA group (80%) relative to CF group (43%) 1336:1376 RESULTS Strain specific PCR indicated a higher prevalence of S. mutans in CA group (80%) relative to CF group (43%). 25191062 7 80 theme CA 1336:1337 arg1 % 1348:1348 80% 1346:1348 80% 1346:1348 RESULTS Strain specific PCR indicated a higher prevalence of S. mutans in CA group (80%) relative to CF group (43%). 25191062 0 81 with children 137:144 arg1 caries 158:163 dental caries 151:163 dental caries from the Southern region of India 151:197 Serotype specific polymerase chain reaction identifies a higher prevalence of streptococcus mutans serotype k and e in a random group of children with dental caries from the Southern region of India. 25191062 8 82 theme serotype 1508:1515 arg1 f 1517:1517 serotype f 1508:1517 serotype f in CA group 1508:1529 Further analysis of the S. mutans positive samples in both groups indicated a higher prevalence of serotype k and e, followed by serotype f in CA group. 25191062 7 83 theme mutans 1326:1331 arg1 prevalence 1309:1318 a higher prevalence 1300:1318 a higher prevalence of S. mutans in CA group (80%) relative to CF group (43%) 1300:1376 RESULTS Strain specific PCR indicated a higher prevalence of S. mutans in CA group (80%) relative to CF group (43%). 25191062 4 84 theme f 802:802 arg1 serotypes 811:819 the e, f, and k serotypes 795:819 the e, f, and k serotypes 795:819 Hence in this study, we have investigated the occurrence of the e, f, and k serotypes in children with or without caries within the age group of 6-12 years. 25191062 8 85 from analysis 1387:1394 arg1 groups 1438:1443 both groups 1433:1443 both groups 1433:1443 Further analysis of the S. mutans positive samples in both groups indicated a higher prevalence of serotype k and e, followed by serotype f in CA group. 25191062 0 86 theme specific 9:16 arg1 reaction 35:42 Serotype specific polymerase chain reaction 0:42 Serotype specific polymerase chain reaction 0:42 Serotype specific polymerase chain reaction identifies a higher prevalence of streptococcus mutans serotype k and e in a random group of children with dental caries from the Southern region of India. 25191062 0 87 dep mutans 92:97 arg1 k 108:108 serotype k 99:108 serotype k 99:108 Serotype specific polymerase chain reaction identifies a higher prevalence of streptococcus mutans serotype k and e in a random group of children with dental caries from the Southern region of India. 25191062 0 87 dep mutans 92:97 arg1 e 114:114 e 114:114 e 114:114 Serotype specific polymerase chain reaction identifies a higher prevalence of streptococcus mutans serotype k and e in a random group of children with dental caries from the Southern region of India. 25191062 5 88 dep active 963:968 arg1 CA 971:972 CA 971:972 CA 971:972 MATERIALS AND METHODS Genomic DNA isolated from whole saliva of caries active (CA) and caries free (CF) groups were first screened for the presence of S. mutans by strain specific polymerase chain reaction (PCR). 25191062 0 89 theme chain 29:33 arg1 reaction 35:42 Serotype specific polymerase chain reaction 0:42 Serotype specific polymerase chain reaction 0:42 Serotype specific polymerase chain reaction identifies a higher prevalence of streptococcus mutans serotype k and e in a random group of children with dental caries from the Southern region of India. 25191062 3 90 theme S. 590:591 arg1 c 609:609 S. mutans serotype c 590:609 S. mutans serotype c 590:609 Although the oral prevalence of S. mutans serotype c in Indian subjects with or without caries is known, the prevalence of the other three serotypes, e, f, and k are not known. 25191062 6 91 theme serotype 1195:1202 arg1 PCR 1213:1215 serotype specific PCR 1195:1215 serotype specific PCR 1195:1215 Those samples that tested positive for the presence of S. mutans were further analyzed by serotype specific PCR to identify the prevalence of the serotypes. 25191062 1 92 theme oral 273:276 arg1 prevalence 278:287 the oral prevalence 269:287 the oral prevalence of Streptococcus mutans 269:311 BACKGROUND The development of dental caries has been associated with the oral prevalence of Streptococcus mutans. 25191062 0 93 theme higher 57:62 arg1 prevalence 64:73 a higher prevalence 55:73 a higher prevalence of streptococcus mutans serotype k and e in a random group of children with dental caries from the Southern region of India 55:197 Serotype specific polymerase chain reaction identifies a higher prevalence of streptococcus mutans serotype k and e in a random group of children with dental caries from the Southern region of India. 25191062 2 94 theme polysaccharides 464:478 arg1 composition 426:436 composition 426:436 composition 426:436 Four serotypes of S. mutans have been reported, namely serotype c, e, f, and k that are classified based on the composition and linkages of cell wall polysaccharides, response to physiological reactions, sero-specificity and 16s rRNA homology. 25191062 2 94 theme polysaccharides 464:478 arg1 linkages 442:449 linkages 442:449 linkages 442:449 Four serotypes of S. mutans have been reported, namely serotype c, e, f, and k that are classified based on the composition and linkages of cell wall polysaccharides, response to physiological reactions, sero-specificity and 16s rRNA homology. 25191062 8 95 from samples 1422:1428 arg1 groups 1438:1443 both groups 1433:1443 both groups 1433:1443 Further analysis of the S. mutans positive samples in both groups indicated a higher prevalence of serotype k and e, followed by serotype f in CA group. 25191062 8 96 theme Further 1379:1385 arg1 analysis 1387:1394 Further analysis 1379:1394 Further analysis of the S. mutans positive samples in both groups 1379:1443 Further analysis of the S. mutans positive samples in both groups indicated a higher prevalence of serotype k and e, followed by serotype f in CA group. 25191062 5 97 theme caries 979:984 arg1 groups 996:1001 caries free (CF) groups 979:1001 caries free (CF) groups 979:1001 MATERIALS AND METHODS Genomic DNA isolated from whole saliva of caries active (CA) and caries free (CF) groups were first screened for the presence of S. mutans by strain specific polymerase chain reaction (PCR). 25191062 0 98 from group 128:132 arg1 prevalence 64:73 a higher prevalence 55:73 a higher prevalence of streptococcus mutans serotype k and e in a random group of children with dental caries from the Southern region of India 55:197 Serotype specific polymerase chain reaction identifies a higher prevalence of streptococcus mutans serotype k and e in a random group of children with dental caries from the Southern region of India. 25191062 3 99 theme serotype 600:607 arg1 c 609:609 S. mutans serotype c 590:609 S. mutans serotype c 590:609 Although the oral prevalence of S. mutans serotype c in Indian subjects with or without caries is known, the prevalence of the other three serotypes, e, f, and k are not known. 25191062 10 100 theme k 1793:1793 arg1 occurrence 1770:1779 the occurrence 1766:1779 the occurrence of serotype k 1766:1793 Besides, the data are also clinically significant as the occurrence of serotype k has been associated with infective endocarditis. 25404483 15 0 dep ord 1648:1650 arg1 order 1624:1628 a novel order 1616:1628 a novel order 1616:1628 nov. and a novel order, Tepidisphaerales ord. 25404483 15 0 dep ord 1648:1650 arg1 nov. 1607:1610 nov. 1607:1610 nov. 1607:1610 nov. and a novel order, Tepidisphaerales ord. 25404483 4 1 theme Baikal 354:359 arg1 region 366:371 Baikal Lake region 354:371 Baikal Lake region 354:371 Three strains of facultatively aerobic, moderately thermophilic bacteria were isolated from terrestrial hot springs in Baikal Lake region and Kamchatka (Russia). 25404483 6 2 from °C 600:601 arg1 growth 584:589 optimal growth 576:589 optimal growth at 47-50 °C and pH 7.0-7.5 576:616 The temperature range for growth was between 20 and 56 °C and the pH range for growth from pH 4.5 to 8.5, with optimal growth at 47-50 °C and pH 7.0-7.5. 25404483 6 3 theme temperature 469:479 arg1 range 481:485 The temperature range 465:485 The temperature range for growth 465:496 The temperature range for growth was between 20 and 56 °C and the pH range for growth from pH 4.5 to 8.5, with optimal growth at 47-50 °C and pH 7.0-7.5. 25404483 9 4 theme % 1085:1085 arg1 values 1061:1066 16S rRNA gene sequence similarity values 1027:1066 16S rRNA gene sequence similarity values of 82.4 and 80.3 % 1027:1085 The phylogenetically closest cultivated relatives were Algisphaera agarilytica 06SJR6-2(T) and Phycisphaera mikurensis FYK2301M01(T) with 16S rRNA gene sequence similarity values of 82.4 and 80.3 %, respectively. 25404483 13 5 theme type 1444:1447 arg1 2842 1459:1462 2842 1459:1462 2842 1459:1462 The type strain is 2842(T) ( = VKM B-2832(T) = JCM 19875(T)). 25404483 13 5 theme type 1444:1447 arg1 strain 1449:1454 The type strain 1440:1454 The type strain 1440:1454 The type strain is 2842(T) ( = VKM B-2832(T) = JCM 19875(T)). 25404483 6 6 from pH 607:608 arg1 growth 584:589 optimal growth 576:589 optimal growth at 47-50 °C and pH 7.0-7.5 576:616 The temperature range for growth was between 20 and 56 °C and the pH range for growth from pH 4.5 to 8.5, with optimal growth at 47-50 °C and pH 7.0-7.5. 25404483 6 7 theme 20 510:511 arg1 °C 520:521 20 and 56 °C 510:521 °C 520:521 The temperature range for growth was between 20 and 56 °C and the pH range for growth from pH 4.5 to 8.5, with optimal growth at 47-50 °C and pH 7.0-7.5. 25404483 11 8 theme Tepidisphaera 1410:1422 arg1 sp 1431:1432 the name Tepidisphaera mucosa sp 1401:1432 the name Tepidisphaera mucosa sp 1401:1432 On the basis of phylogenetic and physiological data, strains 2842(T), 2813 and 2918Kr represent a novel genus and species for which we propose the name Tepidisphaera mucosa sp. 25404483 5 9 theme binary 449:454 arg1 fission 456:462 binary fission 449:462 binary fission 449:462 Cells of the new isolates were cocci reproducing by binary fission. 25404483 4 10 theme terrestrial 327:337 arg1 springs 343:349 terrestrial hot springs 327:349 terrestrial hot springs in Baikal Lake region and Kamchatka (Russia) 327:394 Three strains of facultatively aerobic, moderately thermophilic bacteria were isolated from terrestrial hot springs in Baikal Lake region and Kamchatka (Russia). 25404483 6 11 theme pH 531:532 arg1 range 534:538 the pH range 527:538 the pH range for growth from pH 4.5 to 8.5 527:568 The temperature range for growth was between 20 and 56 °C and the pH range for growth from pH 4.5 to 8.5, with optimal growth at 47-50 °C and pH 7.0-7.5. 25404483 6 12 with °C 520:521 arg1 growth 584:589 optimal growth 576:589 optimal growth at 47-50 °C and pH 7.0-7.5 576:616 The temperature range for growth was between 20 and 56 °C and the pH range for growth from pH 4.5 to 8.5, with optimal growth at 47-50 °C and pH 7.0-7.5. 25404483 5 13 theme new 410:412 arg1 isolates 414:421 the new isolates 406:421 the new isolates 406:421 Cells of the new isolates were cocci reproducing by binary fission. 25404483 1 14 theme family 154:159 arg1 nov. 36:39 nov. 36:39 nov. 36:39 nov., a moderately thermophilic member of the class Phycisphaerae in the phylum Planctomycetes, and proposal of a new family, Tepidisphaeraceae fam. 25404483 1 14 theme family 154:159 arg1 member 68:73 a moderately thermophilic member 42:73 a moderately thermophilic member of the class Phycisphaerae in the phylum Planctomycetes 42:129 nov., a moderately thermophilic member of the class Phycisphaerae in the phylum Planctomycetes, and proposal of a new family, Tepidisphaeraceae fam. 25404483 1 14 theme family 154:159 arg1 proposal 136:143 proposal 136:143 proposal 136:143 nov., a moderately thermophilic member of the class Phycisphaerae in the phylum Planctomycetes, and proposal of a new family, Tepidisphaeraceae fam. 25404483 8 15 theme phylum 866:871 arg1 Planctomycetes 873:886 the phylum Planctomycetes 862:886 the phylum Planctomycetes 862:886 16S rRNA gene sequences of strains 2842, 2813 and 2918Kr were nearly identical (99.7-100 % similarity) and indicated that the strains belonged to the phylum Planctomycetes. 25404483 1 16 theme Tepidisphaeraceae 162:178 arg1 fam 180:182 Tepidisphaeraceae fam 162:182 Tepidisphaeraceae fam 162:182 nov., a moderately thermophilic member of the class Phycisphaerae in the phylum Planctomycetes, and proposal of a new family, Tepidisphaeraceae fam. 25404483 6 17 theme 56 517:518 arg1 °C 520:521 20 and 56 °C 510:521 °C 520:521 The temperature range for growth was between 20 and 56 °C and the pH range for growth from pH 4.5 to 8.5, with optimal growth at 47-50 °C and pH 7.0-7.5. 25404483 11 18 dep strains 1311:1317 arg1 2842 1319:1322 2842 1319:1322 2842(T) 1319:1325 On the basis of phylogenetic and physiological data, strains 2842(T), 2813 and 2918Kr represent a novel genus and species for which we propose the name Tepidisphaera mucosa sp. 25404483 11 18 dep strains 1311:1317 arg1 2918Kr 1337:1342 2918Kr 1337:1342 2918Kr 1337:1342 On the basis of phylogenetic and physiological data, strains 2842(T), 2813 and 2918Kr represent a novel genus and species for which we propose the name Tepidisphaera mucosa sp. 25404483 11 18 dep strains 1311:1317 arg1 T 1324:1324 T 1324:1324 T 1324:1324 On the basis of phylogenetic and physiological data, strains 2842(T), 2813 and 2918Kr represent a novel genus and species for which we propose the name Tepidisphaera mucosa sp. 25404483 11 18 dep strains 1311:1317 arg1 2813 1328:1331 2813 1328:1331 2813 1328:1331 On the basis of phylogenetic and physiological data, strains 2842(T), 2813 and 2918Kr represent a novel genus and species for which we propose the name Tepidisphaera mucosa sp. 25404483 9 19 theme cultivated 918:927 arg1 relatives 929:937 The phylogenetically closest cultivated relatives 889:937 The phylogenetically closest cultivated relatives 889:937 The phylogenetically closest cultivated relatives were Algisphaera agarilytica 06SJR6-2(T) and Phycisphaera mikurensis FYK2301M01(T) with 16S rRNA gene sequence similarity values of 82.4 and 80.3 %, respectively. 25404483 9 19 theme cultivated 918:927 arg1 06SJR6-2 968:975 Algisphaera agarilytica 06SJR6-2 944:975 Algisphaera agarilytica 06SJR6-2(T) 944:978 The phylogenetically closest cultivated relatives were Algisphaera agarilytica 06SJR6-2(T) and Phycisphaera mikurensis FYK2301M01(T) with 16S rRNA gene sequence similarity values of 82.4 and 80.3 %, respectively. 25404483 9 20 with mikurensis 997:1006 arg1 values 1061:1066 16S rRNA gene sequence similarity values 1027:1066 16S rRNA gene sequence similarity values of 82.4 and 80.3 % 1027:1085 The phylogenetically closest cultivated relatives were Algisphaera agarilytica 06SJR6-2(T) and Phycisphaera mikurensis FYK2301M01(T) with 16S rRNA gene sequence similarity values of 82.4 and 80.3 %, respectively. 25404483 1 21 theme phylum 109:114 arg1 Planctomycetes 116:129 the phylum Planctomycetes 105:129 the phylum Planctomycetes 105:129 nov., a moderately thermophilic member of the class Phycisphaerae in the phylum Planctomycetes, and proposal of a new family, Tepidisphaeraceae fam. 25404483 8 22 theme strains 743:749 arg1 sequences 730:738 16S rRNA gene sequences 716:738 16S rRNA gene sequences of strains 2842, 2813 and 2918Kr 716:771 16S rRNA gene sequences of strains 2842, 2813 and 2918Kr were nearly identical (99.7-100 % similarity) and indicated that the strains belonged to the phylum Planctomycetes. 25404483 6 23 from pH 556:557 arg1 growth 544:549 growth 544:549 growth from pH 4.5 to 8.5 544:568 The temperature range for growth was between 20 and 56 °C and the pH range for growth from pH 4.5 to 8.5, with optimal growth at 47-50 °C and pH 7.0-7.5. 25404483 9 24 theme agarilytica 956:966 arg1 relatives 929:937 The phylogenetically closest cultivated relatives 889:937 The phylogenetically closest cultivated relatives 889:937 The phylogenetically closest cultivated relatives were Algisphaera agarilytica 06SJR6-2(T) and Phycisphaera mikurensis FYK2301M01(T) with 16S rRNA gene sequence similarity values of 82.4 and 80.3 %, respectively. 25404483 9 24 theme agarilytica 956:966 arg1 T 977:977 T 977:977 T 977:977 The phylogenetically closest cultivated relatives were Algisphaera agarilytica 06SJR6-2(T) and Phycisphaera mikurensis FYK2301M01(T) with 16S rRNA gene sequence similarity values of 82.4 and 80.3 %, respectively. 25404483 9 24 theme agarilytica 956:966 arg1 06SJR6-2 968:975 Algisphaera agarilytica 06SJR6-2 944:975 Algisphaera agarilytica 06SJR6-2(T) 944:978 The phylogenetically closest cultivated relatives were Algisphaera agarilytica 06SJR6-2(T) and Phycisphaera mikurensis FYK2301M01(T) with 16S rRNA gene sequence similarity values of 82.4 and 80.3 %, respectively. 25404483 2 25 theme new 197:199 arg1 order 201:205 a new order 195:205 a new order 195:205 nov., and a new order, Tepidisphaerales ord. 25404483 4 26 attach isolated 313:320 arg1 springs 343:349 terrestrial hot springs 327:349 terrestrial hot springs in Baikal Lake region and Kamchatka (Russia) 327:394 Three strains of facultatively aerobic, moderately thermophilic bacteria were isolated from terrestrial hot springs in Baikal Lake region and Kamchatka (Russia). 25404483 4 26 attach isolated 313:320 arg2 strains 241:247 Three strains 235:247 Three strains of facultatively aerobic, moderately thermophilic bacteria 235:306 Three strains of facultatively aerobic, moderately thermophilic bacteria were isolated from terrestrial hot springs in Baikal Lake region and Kamchatka (Russia). 25404483 13 27 theme JCM 1487:1489 arg1 19875 1491:1495  = VKM B-2832(T) = JCM 19875 1468:1495  = VKM B-2832(T) = JCM 19875(T) 1468:1498 The type strain is 2842(T) ( = VKM B-2832(T) = JCM 19875(T)). 25404483 13 27 theme JCM 1487:1489 arg1 2842 1459:1462 2842 1459:1462 2842 1459:1462 The type strain is 2842(T) ( = VKM B-2832(T) = JCM 19875(T)). 25404483 13 27 theme JCM 1487:1489 arg1 T 1497:1497 T 1497:1497 T 1497:1497 The type strain is 2842(T) ( = VKM B-2832(T) = JCM 19875(T)). 25404483 10 28 theme growth 1149:1154 arg1 sensitivity 1169:1179 sensitivity 1169:1179 sensitivity to NaCl concentration above 3.0 % 1169:1213 The novel strains differed from them by higher growth temperature, sensitivity to NaCl concentration above 3.0 % and by their cellular fatty acids profile. 25404483 10 28 theme growth 1149:1154 arg1 temperature 1156:1166 higher growth temperature 1142:1166 higher growth temperature 1142:1166 The novel strains differed from them by higher growth temperature, sensitivity to NaCl concentration above 3.0 % and by their cellular fatty acids profile. 25404483 9 29 with 06SJR6-2 968:975 arg1 values 1061:1066 16S rRNA gene sequence similarity values 1027:1066 16S rRNA gene sequence similarity values of 82.4 and 80.3 % 1027:1085 The phylogenetically closest cultivated relatives were Algisphaera agarilytica 06SJR6-2(T) and Phycisphaera mikurensis FYK2301M01(T) with 16S rRNA gene sequence similarity values of 82.4 and 80.3 %, respectively. 25404483 14 30 theme novel 1570:1574 arg1 family 1576:1581 a novel family 1568:1581 a novel family 1568:1581 We also propose that Tepidisphaera gen. nov. is the type genus of a novel family, Tepidisphaeraceae fam. 25404483 14 30 theme novel 1570:1574 arg1 fam 1602:1604 Tepidisphaeraceae fam 1584:1604 Tepidisphaeraceae fam 1584:1604 We also propose that Tepidisphaera gen. nov. is the type genus of a novel family, Tepidisphaeraceae fam. 25404483 6 31 with range 534:538 arg1 growth 584:589 optimal growth 576:589 optimal growth at 47-50 °C and pH 7.0-7.5 576:616 The temperature range for growth was between 20 and 56 °C and the pH range for growth from pH 4.5 to 8.5, with optimal growth at 47-50 °C and pH 7.0-7.5. 25404483 8 32 theme rRNA 720:723 arg1 sequences 730:738 16S rRNA gene sequences 716:738 16S rRNA gene sequences of strains 2842, 2813 and 2918Kr 716:771 16S rRNA gene sequences of strains 2842, 2813 and 2918Kr were nearly identical (99.7-100 % similarity) and indicated that the strains belonged to the phylum Planctomycetes. 25404483 1 33 from Planctomycetes 116:129 arg1 nov. 36:39 nov. 36:39 nov. 36:39 nov., a moderately thermophilic member of the class Phycisphaerae in the phylum Planctomycetes, and proposal of a new family, Tepidisphaeraceae fam. 25404483 1 33 from Planctomycetes 116:129 arg1 member 68:73 a moderately thermophilic member 42:73 a moderately thermophilic member of the class Phycisphaerae in the phylum Planctomycetes 42:129 nov., a moderately thermophilic member of the class Phycisphaerae in the phylum Planctomycetes, and proposal of a new family, Tepidisphaeraceae fam. 25404483 1 33 from Planctomycetes 116:129 arg1 proposal 136:143 proposal 136:143 proposal 136:143 nov., a moderately thermophilic member of the class Phycisphaerae in the phylum Planctomycetes, and proposal of a new family, Tepidisphaeraceae fam. 25404483 9 34 theme Phycisphaera 984:995 arg1 mikurensis 997:1006 Phycisphaera mikurensis FYK2301M01 984:1017 Phycisphaera mikurensis FYK2301M01(T) 984:1020 The phylogenetically closest cultivated relatives were Algisphaera agarilytica 06SJR6-2(T) and Phycisphaera mikurensis FYK2301M01(T) with 16S rRNA gene sequence similarity values of 82.4 and 80.3 %, respectively. 25404483 9 34 theme Phycisphaera 984:995 arg1 T 1019:1019 T 1019:1019 T 1019:1019 The phylogenetically closest cultivated relatives were Algisphaera agarilytica 06SJR6-2(T) and Phycisphaera mikurensis FYK2301M01(T) with 16S rRNA gene sequence similarity values of 82.4 and 80.3 %, respectively. 25404483 1 35 theme thermophilic 55:66 arg1 member 68:73 a moderately thermophilic member 42:73 a moderately thermophilic member of the class Phycisphaerae in the phylum Planctomycetes 42:129 nov., a moderately thermophilic member of the class Phycisphaerae in the phylum Planctomycetes, and proposal of a new family, Tepidisphaeraceae fam. 25404483 1 35 theme thermophilic 55:66 arg1 nov. 36:39 nov. 36:39 nov. 36:39 nov., a moderately thermophilic member of the class Phycisphaerae in the phylum Planctomycetes, and proposal of a new family, Tepidisphaeraceae fam. 25404483 4 36 dep aerobic 266:272 arg1 thermophilic 286:297 thermophilic 286:297 thermophilic 286:297 Three strains of facultatively aerobic, moderately thermophilic bacteria were isolated from terrestrial hot springs in Baikal Lake region and Kamchatka (Russia). 25404483 0 37 theme Tepidisphaera 0:12 arg1 nov. 26:29 Tepidisphaera mucosa gen. nov. 0:29 Tepidisphaera mucosa gen. nov. 0:29 Tepidisphaera mucosa gen. nov., sp. 25404483 1 38 from Phycisphaerae 88:100 arg1 Planctomycetes 116:129 the phylum Planctomycetes 105:129 the phylum Planctomycetes 105:129 nov., a moderately thermophilic member of the class Phycisphaerae in the phylum Planctomycetes, and proposal of a new family, Tepidisphaeraceae fam. 25404483 8 39 theme 99.7-100 796:803 arg1 % 805:805 % 805:805 % 805:805 16S rRNA gene sequences of strains 2842, 2813 and 2918Kr were nearly identical (99.7-100 % similarity) and indicated that the strains belonged to the phylum Planctomycetes. 25404483 0 40 theme gen. 21:24 arg1 nov. 26:29 Tepidisphaera mucosa gen. nov. 0:29 Tepidisphaera mucosa gen. nov. 0:29 Tepidisphaera mucosa gen. nov., sp. 25404483 1 41 theme class 82:86 arg1 Phycisphaerae 88:100 the class Phycisphaerae 78:100 the class Phycisphaerae in the phylum Planctomycetes 78:129 nov., a moderately thermophilic member of the class Phycisphaerae in the phylum Planctomycetes, and proposal of a new family, Tepidisphaeraceae fam. 25404483 13 42 theme VKM 1471:1473 arg1 19875 1491:1495  = VKM B-2832(T) = JCM 19875 1468:1495  = VKM B-2832(T) = JCM 19875(T) 1468:1498 The type strain is 2842(T) ( = VKM B-2832(T) = JCM 19875(T)). 25404483 13 42 theme VKM 1471:1473 arg1 2842 1459:1462 2842 1459:1462 2842 1459:1462 The type strain is 2842(T) ( = VKM B-2832(T) = JCM 19875(T)). 25404483 13 42 theme VKM 1471:1473 arg1 T 1497:1497 T 1497:1497 T 1497:1497 The type strain is 2842(T) ( = VKM B-2832(T) = JCM 19875(T)). 25404483 9 43 theme rRNA 1031:1034 arg1 similarity 1050:1059 16S rRNA gene sequence similarity 1027:1059 16S rRNA gene sequence similarity values of 82.4 and 80.3 % 1027:1085 The phylogenetically closest cultivated relatives were Algisphaera agarilytica 06SJR6-2(T) and Phycisphaera mikurensis FYK2301M01(T) with 16S rRNA gene sequence similarity values of 82.4 and 80.3 %, respectively. 25404483 8 44 dep identical 785:793 arg1 similarity 807:816 99.7-100 % similarity 796:816 99.7-100 % similarity 796:816 16S rRNA gene sequences of strains 2842, 2813 and 2918Kr were nearly identical (99.7-100 % similarity) and indicated that the strains belonged to the phylum Planctomycetes. 25404483 1 45 dep fam 180:182 arg1 proposal 136:143 proposal 136:143 proposal 136:143 nov., a moderately thermophilic member of the class Phycisphaerae in the phylum Planctomycetes, and proposal of a new family, Tepidisphaeraceae fam. 25404483 1 45 dep fam 180:182 arg1 member 68:73 a moderately thermophilic member 42:73 a moderately thermophilic member of the class Phycisphaerae in the phylum Planctomycetes 42:129 nov., a moderately thermophilic member of the class Phycisphaerae in the phylum Planctomycetes, and proposal of a new family, Tepidisphaeraceae fam. 25404483 1 45 dep fam 180:182 arg1 nov. 36:39 nov. 36:39 nov. 36:39 nov., a moderately thermophilic member of the class Phycisphaerae in the phylum Planctomycetes, and proposal of a new family, Tepidisphaeraceae fam. 25404483 9 46 theme sequence 1041:1048 arg1 similarity 1050:1059 16S rRNA gene sequence similarity 1027:1059 16S rRNA gene sequence similarity values of 82.4 and 80.3 % 1027:1085 The phylogenetically closest cultivated relatives were Algisphaera agarilytica 06SJR6-2(T) and Phycisphaera mikurensis FYK2301M01(T) with 16S rRNA gene sequence similarity values of 82.4 and 80.3 %, respectively. 25404483 14 47 theme Tepidisphaera 1523:1535 arg1 genus 1559:1563 the type genus 1550:1563 the type genus of a novel family, Tepidisphaeraceae fam 1550:1604 We also propose that Tepidisphaera gen. nov. is the type genus of a novel family, Tepidisphaeraceae fam. 25404483 14 47 theme Tepidisphaera 1523:1535 arg1 nov. 1542:1545 Tepidisphaera gen. nov. 1523:1545 Tepidisphaera gen. nov. 1523:1545 We also propose that Tepidisphaera gen. nov. is the type genus of a novel family, Tepidisphaeraceae fam. 25404483 10 48 theme cellular 1228:1235 arg1 acids 1243:1247 their cellular fatty acids 1222:1247 their cellular fatty acids 1222:1247 The novel strains differed from them by higher growth temperature, sensitivity to NaCl concentration above 3.0 % and by their cellular fatty acids profile. 25404483 10 49 theme fatty 1237:1241 arg1 acids 1243:1247 their cellular fatty acids 1222:1247 their cellular fatty acids 1222:1247 The novel strains differed from them by higher growth temperature, sensitivity to NaCl concentration above 3.0 % and by their cellular fatty acids profile. 25404483 10 50 theme novel 1106:1110 arg1 strains 1112:1118 The novel strains 1102:1118 The novel strains 1102:1118 The novel strains differed from them by higher growth temperature, sensitivity to NaCl concentration above 3.0 % and by their cellular fatty acids profile. 25404483 4 51 theme Lake 361:364 arg1 region 366:371 Baikal Lake region 354:371 Baikal Lake region 354:371 Three strains of facultatively aerobic, moderately thermophilic bacteria were isolated from terrestrial hot springs in Baikal Lake region and Kamchatka (Russia). 25404483 11 52 theme physiological 1291:1303 arg1 data 1305:1308 phylogenetic and physiological data 1274:1308 phylogenetic and physiological data 1274:1308 On the basis of phylogenetic and physiological data, strains 2842(T), 2813 and 2918Kr represent a novel genus and species for which we propose the name Tepidisphaera mucosa sp. 25404483 11 53 theme phylogenetic 1274:1285 arg1 data 1305:1308 phylogenetic and physiological data 1274:1308 phylogenetic and physiological data 1274:1308 On the basis of phylogenetic and physiological data, strains 2842(T), 2813 and 2918Kr represent a novel genus and species for which we propose the name Tepidisphaera mucosa sp. 25404483 4 54 theme hot 339:341 arg1 springs 343:349 terrestrial hot springs 327:349 terrestrial hot springs in Baikal Lake region and Kamchatka (Russia) 327:394 Three strains of facultatively aerobic, moderately thermophilic bacteria were isolated from terrestrial hot springs in Baikal Lake region and Kamchatka (Russia). 25404483 11 55 theme mucosa 1424:1429 arg1 sp 1431:1432 the name Tepidisphaera mucosa sp 1401:1432 the name Tepidisphaera mucosa sp 1401:1432 On the basis of phylogenetic and physiological data, strains 2842(T), 2813 and 2918Kr represent a novel genus and species for which we propose the name Tepidisphaera mucosa sp. 25404483 1 56 theme new 150:152 arg1 family 154:159 a new family 148:159 a new family 148:159 nov., a moderately thermophilic member of the class Phycisphaerae in the phylum Planctomycetes, and proposal of a new family, Tepidisphaeraceae fam. 25404483 4 57 from springs 343:349 arg1 Russia 388:393 Russia 388:393 Russia 388:393 Three strains of facultatively aerobic, moderately thermophilic bacteria were isolated from terrestrial hot springs in Baikal Lake region and Kamchatka (Russia). 25404483 4 57 from springs 343:349 arg1 Kamchatka 377:385 Kamchatka 377:385 Kamchatka (Russia) 377:394 Three strains of facultatively aerobic, moderately thermophilic bacteria were isolated from terrestrial hot springs in Baikal Lake region and Kamchatka (Russia). 25404483 4 57 from springs 343:349 arg1 region 366:371 Baikal Lake region 354:371 Baikal Lake region 354:371 Three strains of facultatively aerobic, moderately thermophilic bacteria were isolated from terrestrial hot springs in Baikal Lake region and Kamchatka (Russia). 25404483 11 58 theme name 1405:1408 arg1 sp 1431:1432 the name Tepidisphaera mucosa sp 1401:1432 the name Tepidisphaera mucosa sp 1401:1432 On the basis of phylogenetic and physiological data, strains 2842(T), 2813 and 2918Kr represent a novel genus and species for which we propose the name Tepidisphaera mucosa sp. 25404483 5 59 theme isolates 414:421 arg1 Cells 397:401 Cells 397:401 Cells of the new isolates 397:421 Cells of the new isolates were cocci reproducing by binary fission. 25404483 11 60 theme novel 1356:1360 arg1 genus 1362:1366 a novel genus 1354:1366 a novel genus 1354:1366 On the basis of phylogenetic and physiological data, strains 2842(T), 2813 and 2918Kr represent a novel genus and species for which we propose the name Tepidisphaera mucosa sp. 25404483 9 61 theme closest 910:916 arg1 relatives 929:937 The phylogenetically closest cultivated relatives 889:937 The phylogenetically closest cultivated relatives 889:937 The phylogenetically closest cultivated relatives were Algisphaera agarilytica 06SJR6-2(T) and Phycisphaera mikurensis FYK2301M01(T) with 16S rRNA gene sequence similarity values of 82.4 and 80.3 %, respectively. 25404483 9 61 theme closest 910:916 arg1 06SJR6-2 968:975 Algisphaera agarilytica 06SJR6-2 944:975 Algisphaera agarilytica 06SJR6-2(T) 944:978 The phylogenetically closest cultivated relatives were Algisphaera agarilytica 06SJR6-2(T) and Phycisphaera mikurensis FYK2301M01(T) with 16S rRNA gene sequence similarity values of 82.4 and 80.3 %, respectively. 25404483 1 62 theme Phycisphaerae 88:100 arg1 nov. 36:39 nov. 36:39 nov. 36:39 nov., a moderately thermophilic member of the class Phycisphaerae in the phylum Planctomycetes, and proposal of a new family, Tepidisphaeraceae fam. 25404483 1 62 theme Phycisphaerae 88:100 arg1 member 68:73 a moderately thermophilic member 42:73 a moderately thermophilic member of the class Phycisphaerae in the phylum Planctomycetes 42:129 nov., a moderately thermophilic member of the class Phycisphaerae in the phylum Planctomycetes, and proposal of a new family, Tepidisphaeraceae fam. 25404483 1 62 theme Phycisphaerae 88:100 arg1 proposal 136:143 proposal 136:143 proposal 136:143 nov., a moderately thermophilic member of the class Phycisphaerae in the phylum Planctomycetes, and proposal of a new family, Tepidisphaeraceae fam. 25404483 6 63 dep pH 556:557 arg1 to 563:564 to 563:564 to 563:564 The temperature range for growth was between 20 and 56 °C and the pH range for growth from pH 4.5 to 8.5, with optimal growth at 47-50 °C and pH 7.0-7.5. 25404483 8 64 theme gene 725:728 arg1 sequences 730:738 16S rRNA gene sequences 716:738 16S rRNA gene sequences of strains 2842, 2813 and 2918Kr 716:771 16S rRNA gene sequences of strains 2842, 2813 and 2918Kr were nearly identical (99.7-100 % similarity) and indicated that the strains belonged to the phylum Planctomycetes. 25404483 11 65 dep data 1305:1308 arg1 basis 1265:1269 basis 1265:1269 basis 1265:1269 On the basis of phylogenetic and physiological data, strains 2842(T), 2813 and 2918Kr represent a novel genus and species for which we propose the name Tepidisphaera mucosa sp. 25404483 11 65 dep data 1305:1308 arg1 the 1261:1263 the 1261:1263 the 1261:1263 On the basis of phylogenetic and physiological data, strains 2842(T), 2813 and 2918Kr represent a novel genus and species for which we propose the name Tepidisphaera mucosa sp. 25404483 9 66 theme Algisphaera 944:954 arg1 relatives 929:937 The phylogenetically closest cultivated relatives 889:937 The phylogenetically closest cultivated relatives 889:937 The phylogenetically closest cultivated relatives were Algisphaera agarilytica 06SJR6-2(T) and Phycisphaera mikurensis FYK2301M01(T) with 16S rRNA gene sequence similarity values of 82.4 and 80.3 %, respectively. 25404483 9 66 theme Algisphaera 944:954 arg1 T 977:977 T 977:977 T 977:977 The phylogenetically closest cultivated relatives were Algisphaera agarilytica 06SJR6-2(T) and Phycisphaera mikurensis FYK2301M01(T) with 16S rRNA gene sequence similarity values of 82.4 and 80.3 %, respectively. 25404483 9 66 theme Algisphaera 944:954 arg1 06SJR6-2 968:975 Algisphaera agarilytica 06SJR6-2 944:975 Algisphaera agarilytica 06SJR6-2(T) 944:978 The phylogenetically closest cultivated relatives were Algisphaera agarilytica 06SJR6-2(T) and Phycisphaera mikurensis FYK2301M01(T) with 16S rRNA gene sequence similarity values of 82.4 and 80.3 %, respectively. 25404483 14 67 theme Tepidisphaeraceae 1584:1600 arg1 family 1576:1581 a novel family 1568:1581 a novel family 1568:1581 We also propose that Tepidisphaera gen. nov. is the type genus of a novel family, Tepidisphaeraceae fam. 25404483 14 67 theme Tepidisphaeraceae 1584:1600 arg1 fam 1602:1604 Tepidisphaeraceae fam 1584:1604 Tepidisphaeraceae fam 1584:1604 We also propose that Tepidisphaera gen. nov. is the type genus of a novel family, Tepidisphaeraceae fam. 25404483 14 68 theme family 1576:1581 arg1 genus 1559:1563 the type genus 1550:1563 the type genus of a novel family, Tepidisphaeraceae fam 1550:1604 We also propose that Tepidisphaera gen. nov. is the type genus of a novel family, Tepidisphaeraceae fam. 25404483 14 68 theme family 1576:1581 arg1 nov. 1542:1545 Tepidisphaera gen. nov. 1523:1545 Tepidisphaera gen. nov. 1523:1545 We also propose that Tepidisphaera gen. nov. is the type genus of a novel family, Tepidisphaeraceae fam. 25404483 10 69 theme higher 1142:1147 arg1 sensitivity 1169:1179 sensitivity 1169:1179 sensitivity to NaCl concentration above 3.0 % 1169:1213 The novel strains differed from them by higher growth temperature, sensitivity to NaCl concentration above 3.0 % and by their cellular fatty acids profile. 25404483 10 69 theme higher 1142:1147 arg1 temperature 1156:1166 higher growth temperature 1142:1166 higher growth temperature 1142:1166 The novel strains differed from them by higher growth temperature, sensitivity to NaCl concentration above 3.0 % and by their cellular fatty acids profile. 25404483 1 70 from proposal 136:143 arg1 Planctomycetes 116:129 the phylum Planctomycetes 105:129 the phylum Planctomycetes 105:129 nov., a moderately thermophilic member of the class Phycisphaerae in the phylum Planctomycetes, and proposal of a new family, Tepidisphaeraceae fam. 25404483 8 71 dep strains 743:749 arg1 2918Kr 766:771 2918Kr 766:771 2918Kr 766:771 16S rRNA gene sequences of strains 2842, 2813 and 2918Kr were nearly identical (99.7-100 % similarity) and indicated that the strains belonged to the phylum Planctomycetes. 25404483 8 71 dep strains 743:749 arg1 2813 757:760 2813 757:760 2813 757:760 16S rRNA gene sequences of strains 2842, 2813 and 2918Kr were nearly identical (99.7-100 % similarity) and indicated that the strains belonged to the phylum Planctomycetes. 25404483 8 71 dep strains 743:749 arg1 2842 751:754 2842 751:754 2842 751:754 16S rRNA gene sequences of strains 2842, 2813 and 2918Kr were nearly identical (99.7-100 % similarity) and indicated that the strains belonged to the phylum Planctomycetes. 25404483 10 72 theme NaCl 1184:1187 arg1 concentration 1189:1201 NaCl concentration 1184:1201 NaCl concentration 1184:1201 The novel strains differed from them by higher growth temperature, sensitivity to NaCl concentration above 3.0 % and by their cellular fatty acids profile. 25404483 8 73 theme 16S 716:718 arg1 sequences 730:738 16S rRNA gene sequences 716:738 16S rRNA gene sequences of strains 2842, 2813 and 2918Kr 716:771 16S rRNA gene sequences of strains 2842, 2813 and 2918Kr were nearly identical (99.7-100 % similarity) and indicated that the strains belonged to the phylum Planctomycetes. 25404483 13 74 theme T 1482:1482 arg1 19875 1491:1495  = VKM B-2832(T) = JCM 19875 1468:1495  = VKM B-2832(T) = JCM 19875(T) 1468:1498 The type strain is 2842(T) ( = VKM B-2832(T) = JCM 19875(T)). 25404483 13 74 theme T 1482:1482 arg1 2842 1459:1462 2842 1459:1462 2842 1459:1462 The type strain is 2842(T) ( = VKM B-2832(T) = JCM 19875(T)). 25404483 13 74 theme T 1482:1482 arg1 T 1497:1497 T 1497:1497 T 1497:1497 The type strain is 2842(T) ( = VKM B-2832(T) = JCM 19875(T)). 25404483 0 75 theme mucosa 14:19 arg1 nov. 26:29 Tepidisphaera mucosa gen. nov. 0:29 Tepidisphaera mucosa gen. nov. 0:29 Tepidisphaera mucosa gen. nov., sp. 25404483 13 76 theme  = 1484:1485 arg1 19875 1491:1495  = VKM B-2832(T) = JCM 19875 1468:1495  = VKM B-2832(T) = JCM 19875(T) 1468:1498 The type strain is 2842(T) ( = VKM B-2832(T) = JCM 19875(T)). 25404483 13 76 theme  = 1484:1485 arg1 2842 1459:1462 2842 1459:1462 2842 1459:1462 The type strain is 2842(T) ( = VKM B-2832(T) = JCM 19875(T)). 25404483 13 76 theme  = 1484:1485 arg1 T 1497:1497 T 1497:1497 T 1497:1497 The type strain is 2842(T) ( = VKM B-2832(T) = JCM 19875(T)). 25404483 13 77 theme  = 1468:1469 arg1 19875 1491:1495  = VKM B-2832(T) = JCM 19875 1468:1495  = VKM B-2832(T) = JCM 19875(T) 1468:1498 The type strain is 2842(T) ( = VKM B-2832(T) = JCM 19875(T)). 25404483 13 77 theme  = 1468:1469 arg1 2842 1459:1462 2842 1459:1462 2842 1459:1462 The type strain is 2842(T) ( = VKM B-2832(T) = JCM 19875(T)). 25404483 13 77 theme  = 1468:1469 arg1 T 1497:1497 T 1497:1497 T 1497:1497 The type strain is 2842(T) ( = VKM B-2832(T) = JCM 19875(T)). 25404483 6 78 theme optimal 576:582 arg1 growth 584:589 optimal growth 576:589 optimal growth at 47-50 °C and pH 7.0-7.5 576:616 The temperature range for growth was between 20 and 56 °C and the pH range for growth from pH 4.5 to 8.5, with optimal growth at 47-50 °C and pH 7.0-7.5. 25404483 14 79 theme type 1554:1557 arg1 genus 1559:1563 the type genus 1550:1563 the type genus of a novel family, Tepidisphaeraceae fam 1550:1604 We also propose that Tepidisphaera gen. nov. is the type genus of a novel family, Tepidisphaeraceae fam. 25404483 14 79 theme type 1554:1557 arg1 nov. 1542:1545 Tepidisphaera gen. nov. 1523:1545 Tepidisphaera gen. nov. 1523:1545 We also propose that Tepidisphaera gen. nov. is the type genus of a novel family, Tepidisphaeraceae fam. 25404483 8 80 theme % 805:805 arg1 similarity 807:816 99.7-100 % similarity 796:816 99.7-100 % similarity 796:816 16S rRNA gene sequences of strains 2842, 2813 and 2918Kr were nearly identical (99.7-100 % similarity) and indicated that the strains belonged to the phylum Planctomycetes. 25404483 13 81 theme B-2832 1475:1480 arg1 19875 1491:1495  = VKM B-2832(T) = JCM 19875 1468:1495  = VKM B-2832(T) = JCM 19875(T) 1468:1498 The type strain is 2842(T) ( = VKM B-2832(T) = JCM 19875(T)). 25404483 13 81 theme B-2832 1475:1480 arg1 2842 1459:1462 2842 1459:1462 2842 1459:1462 The type strain is 2842(T) ( = VKM B-2832(T) = JCM 19875(T)). 25404483 13 81 theme B-2832 1475:1480 arg1 T 1497:1497 T 1497:1497 T 1497:1497 The type strain is 2842(T) ( = VKM B-2832(T) = JCM 19875(T)). 25404483 9 82 theme 16S 1027:1029 arg1 similarity 1050:1059 16S rRNA gene sequence similarity 1027:1059 16S rRNA gene sequence similarity values of 82.4 and 80.3 % 1027:1085 The phylogenetically closest cultivated relatives were Algisphaera agarilytica 06SJR6-2(T) and Phycisphaera mikurensis FYK2301M01(T) with 16S rRNA gene sequence similarity values of 82.4 and 80.3 %, respectively. 25404483 7 83 theme growth 697:702 arg1 polysaccharides 678:692 polysaccharides 678:692 polysaccharides 678:692 The organisms were chemoheterotrophs preferring sugars and polysaccharides as growth substrates. 25404483 7 83 theme growth 697:702 arg1 substrates 704:713 growth substrates 697:713 growth substrates 697:713 The organisms were chemoheterotrophs preferring sugars and polysaccharides as growth substrates. 25404483 7 83 theme growth 697:702 arg1 sugars 667:672 sugars 667:672 sugars 667:672 The organisms were chemoheterotrophs preferring sugars and polysaccharides as growth substrates. 25404483 0 84 dep sp 32:33 arg1 nov. 26:29 Tepidisphaera mucosa gen. nov. 0:29 Tepidisphaera mucosa gen. nov. 0:29 Tepidisphaera mucosa gen. nov., sp. 25404483 4 85 theme bacteria 299:306 arg1 strains 241:247 Three strains 235:247 Three strains of facultatively aerobic, moderately thermophilic bacteria 235:306 Three strains of facultatively aerobic, moderately thermophilic bacteria were isolated from terrestrial hot springs in Baikal Lake region and Kamchatka (Russia). 25404483 9 86 theme gene 1036:1039 arg1 similarity 1050:1059 16S rRNA gene sequence similarity 1027:1059 16S rRNA gene sequence similarity values of 82.4 and 80.3 % 1027:1085 The phylogenetically closest cultivated relatives were Algisphaera agarilytica 06SJR6-2(T) and Phycisphaera mikurensis FYK2301M01(T) with 16S rRNA gene sequence similarity values of 82.4 and 80.3 %, respectively. 25404483 14 87 theme gen. 1537:1540 arg1 genus 1559:1563 the type genus 1550:1563 the type genus of a novel family, Tepidisphaeraceae fam 1550:1604 We also propose that Tepidisphaera gen. nov. is the type genus of a novel family, Tepidisphaeraceae fam. 25404483 14 87 theme gen. 1537:1540 arg1 nov. 1542:1545 Tepidisphaera gen. nov. 1523:1545 Tepidisphaera gen. nov. 1523:1545 We also propose that Tepidisphaera gen. nov. is the type genus of a novel family, Tepidisphaeraceae fam. 25404483 9 88 theme similarity 1050:1059 arg1 values 1061:1066 16S rRNA gene sequence similarity values 1027:1066 16S rRNA gene sequence similarity values of 82.4 and 80.3 % 1027:1085 The phylogenetically closest cultivated relatives were Algisphaera agarilytica 06SJR6-2(T) and Phycisphaera mikurensis FYK2301M01(T) with 16S rRNA gene sequence similarity values of 82.4 and 80.3 %, respectively. 25404483 1 89 from member 68:73 arg1 Planctomycetes 116:129 the phylum Planctomycetes 105:129 the phylum Planctomycetes 105:129 nov., a moderately thermophilic member of the class Phycisphaerae in the phylum Planctomycetes, and proposal of a new family, Tepidisphaeraceae fam. 25404483 15 90 theme novel 1618:1622 arg1 order 1624:1628 a novel order 1616:1628 a novel order 1616:1628 nov. and a novel order, Tepidisphaerales ord. 25404483 4 91 theme aerobic 266:272 arg1 bacteria 299:306 facultatively aerobic, moderately thermophilic bacteria 252:306 facultatively aerobic, moderately thermophilic bacteria 252:306 Three strains of facultatively aerobic, moderately thermophilic bacteria were isolated from terrestrial hot springs in Baikal Lake region and Kamchatka (Russia). 26961584 8 0 theme molar 971:975 arg1 ratio 977:981 a molar ratio 969:981 a molar ratio of 1.0:1.5:1.4:1.8:0.7 969:1004 The cell wall of strain F4T contained glutamic acid, serine, glycine, alanine and ornithine in a molar ratio of 1.0:1.5:1.4:1.8:0.7. 26961584 11 1 theme Detailed 1229:1236 arg1 analysis 1251:1258 Detailed phylogenetic analysis 1229:1258 Detailed phylogenetic analysis based on 16S rRNA gene sequences 1229:1291 Detailed phylogenetic analysis based on 16S rRNA gene sequences indicated that strain F4T belongs to the genus Thermosporothrix, and that it was related most closely to Thermosporothrix hazakensis SK20-1T (98.7 % similarity). 26961584 8 2 theme cell 878:881 arg1 wall 883:886 The cell wall 874:886 The cell wall of strain F4T 874:900 The cell wall of strain F4T contained glutamic acid, serine, glycine, alanine and ornithine in a molar ratio of 1.0:1.5:1.4:1.8:0.7. 26961584 9 3 theme unknown 1180:1186 arg1 lipids 1188:1193 two unknown lipids 1176:1193 two unknown lipids 1176:1193 The polar lipids of this strain consisted of phosphatidylglycerol, diphosphatidylglycerol, phosphatidylinositol, one unknown phospholipid, three unknown glycolipids and two unknown lipids. 26961584 12 4 theme DNA-DNA 1455:1461 arg1 hybridization 1463:1475 DNA-DNA hybridization 1455:1475 DNA-DNA hybridization 1455:1475 DNA-DNA hybridization showed relatedness values of less than 15 % with the type strain of Thermosporothrix hazakensis. 26961584 12 5 theme type 1530:1533 arg1 strain 1535:1540 the type strain 1526:1540 the type strain of Thermosporothrix hazakensis 1526:1571 DNA-DNA hybridization showed relatedness values of less than 15 % with the type strain of Thermosporothrix hazakensis. 26961584 11 6 theme phylogenetic 1238:1249 arg1 analysis 1251:1258 Detailed phylogenetic analysis 1229:1258 Detailed phylogenetic analysis based on 16S rRNA gene sequences 1229:1291 Detailed phylogenetic analysis based on 16S rRNA gene sequences indicated that strain F4T belongs to the genus Thermosporothrix, and that it was related most closely to Thermosporothrix hazakensis SK20-1T (98.7 % similarity). 26961584 6 7 theme G+C 744:746 arg1 content 748:754 The G+C content 740:754 The G+C content in the DNA of strain F4T 740:779 The G+C content in the DNA of strain F4T was 52.5 mol%. 26961584 6 7 theme G+C 744:746 arg1 % 793:793 52.5 mol% 785:793 52.5 mol% 785:793 The G+C content in the DNA of strain F4T was 52.5 mol%. 26961584 8 8 from ornithine 956:964 arg1 ratio 977:981 a molar ratio 969:981 a molar ratio of 1.0:1.5:1.4:1.8:0.7 969:1004 The cell wall of strain F4T contained glutamic acid, serine, glycine, alanine and ornithine in a molar ratio of 1.0:1.5:1.4:1.8:0.7. 26961584 12 9 theme Thermosporothrix 1545:1560 arg1 hazakensis 1562:1571 Thermosporothrix hazakensis 1545:1571 Thermosporothrix hazakensis 1545:1571 DNA-DNA hybridization showed relatedness values of less than 15 % with the type strain of Thermosporothrix hazakensis. 26961584 8 10 from alanine 944:950 arg1 ratio 977:981 a molar ratio 969:981 a molar ratio of 1.0:1.5:1.4:1.8:0.7 969:1004 The cell wall of strain F4T contained glutamic acid, serine, glycine, alanine and ornithine in a molar ratio of 1.0:1.5:1.4:1.8:0.7. 26961584 11 11 theme rRNA 1273:1276 arg1 sequences 1283:1291 16S rRNA gene sequences 1269:1291 16S rRNA gene sequences 1269:1291 Detailed phylogenetic analysis based on 16S rRNA gene sequences indicated that strain F4T belongs to the genus Thermosporothrix, and that it was related most closely to Thermosporothrix hazakensis SK20-1T (98.7 % similarity). 26961584 9 12 theme unknown 1152:1158 arg1 glycolipids 1160:1170 three unknown glycolipids 1146:1170 three unknown glycolipids 1146:1170 The polar lipids of this strain consisted of phosphatidylglycerol, diphosphatidylglycerol, phosphatidylinositol, one unknown phospholipid, three unknown glycolipids and two unknown lipids. 26961584 9 13 theme polar 1011:1015 arg1 lipids 1017:1022 The polar lipids 1007:1022 The polar lipids of this strain 1007:1037 The polar lipids of this strain consisted of phosphatidylglycerol, diphosphatidylglycerol, phosphatidylinositol, one unknown phospholipid, three unknown glycolipids and two unknown lipids. 26961584 11 14 theme gene 1278:1281 arg1 sequences 1283:1291 16S rRNA gene sequences 1269:1291 16S rRNA gene sequences 1269:1291 Detailed phylogenetic analysis based on 16S rRNA gene sequences indicated that strain F4T belongs to the genus Thermosporothrix, and that it was related most closely to Thermosporothrix hazakensis SK20-1T (98.7 % similarity). 26961584 6 15 theme mol 790:792 arg1 content 748:754 The G+C content 740:754 The G+C content in the DNA of strain F4T 740:779 The G+C content in the DNA of strain F4T was 52.5 mol%. 26961584 6 15 theme mol 790:792 arg1 % 793:793 52.5 mol% 785:793 52.5 mol% 785:793 The G+C content in the DNA of strain F4T was 52.5 mol%. 26961584 1 16 theme class 57:61 arg1 Ktedonobacteria 63:77 the class Ktedonobacteria 53:77 the class Ktedonobacteria 53:77 nov., belonging to the class Ktedonobacteria, isolated from fallen leaves on geothermal soil, and emended description of the genus Thermosporothrix. 26961584 12 17 theme % 1519:1519 arg1 values 1496:1501 relatedness values 1484:1501 relatedness values of less than 15 % 1484:1519 DNA-DNA hybridization showed relatedness values of less than 15 % with the type strain of Thermosporothrix hazakensis. 26961584 8 18 from glycine 935:941 arg1 ratio 977:981 a molar ratio 969:981 a molar ratio of 1.0:1.5:1.4:1.8:0.7 969:1004 The cell wall of strain F4T contained glutamic acid, serine, glycine, alanine and ornithine in a molar ratio of 1.0:1.5:1.4:1.8:0.7. 26961584 8 19 theme F4T 898:900 arg1 wall 883:886 The cell wall 874:886 The cell wall of strain F4T 874:900 The cell wall of strain F4T contained glutamic acid, serine, glycine, alanine and ornithine in a molar ratio of 1.0:1.5:1.4:1.8:0.7. 26961584 11 20 theme strain 1308:1313 arg1 F4T 1315:1317 strain F4T 1308:1317 strain F4T 1308:1317 Detailed phylogenetic analysis based on 16S rRNA gene sequences indicated that strain F4T belongs to the genus Thermosporothrix, and that it was related most closely to Thermosporothrix hazakensis SK20-1T (98.7 % similarity). 26961584 3 21 theme growth 427:432 arg1 temperature 434:444 optimum growth temperature 419:444 optimum growth temperature 419:444 This strain, designated F4T, grew at temperatures between 30 and 60 °C; optimum growth temperature was 50 °C, whereas no growth was observed below 28 °C or above 65 °C. 26961584 8 22 theme 1.0:1.5:1.4:1.8:0.7 986:1004 arg1 ratio 977:981 a molar ratio 969:981 a molar ratio of 1.0:1.5:1.4:1.8:0.7 969:1004 The cell wall of strain F4T contained glutamic acid, serine, glycine, alanine and ornithine in a molar ratio of 1.0:1.5:1.4:1.8:0.7. 26961584 8 23 theme strain 891:896 arg1 F4T 898:900 strain F4T 891:900 strain F4T 891:900 The cell wall of strain F4T contained glutamic acid, serine, glycine, alanine and ornithine in a molar ratio of 1.0:1.5:1.4:1.8:0.7. 26961584 2 24 theme aerial 280:285 arg1 mycelia 287:293 branched vegetative and aerial mycelia 256:293 branched vegetative and aerial mycelia 256:293 A thermophilic, Gram-stain-positive, spore-forming bacterium that formed branched vegetative and aerial mycelia was isolated from fallen leaves on geothermal soil. 26961584 1 25 theme genus 159:163 arg1 Thermosporothrix 165:180 the genus Thermosporothrix 155:180 the genus Thermosporothrix 155:180 nov., belonging to the class Ktedonobacteria, isolated from fallen leaves on geothermal soil, and emended description of the genus Thermosporothrix. 26961584 0 26 theme narukonensis 17:28 arg1 sp 30:31 Thermosporothrix narukonensis sp 0:31 Thermosporothrix narukonensis sp. 0:32 Thermosporothrix narukonensis sp. 26961584 6 27 theme F4T 777:779 arg1 DNA 763:765 the DNA 759:765 the DNA of strain F4T 759:779 The G+C content in the DNA of strain F4T was 52.5 mol%. 26961584 8 28 theme glutamic 912:919 arg1 acid 921:924 glutamic acid 912:924 glutamic acid 912:924 The cell wall of strain F4T contained glutamic acid, serine, glycine, alanine and ornithine in a molar ratio of 1.0:1.5:1.4:1.8:0.7. 26961584 9 29 theme strain 1032:1037 arg1 lipids 1017:1022 The polar lipids 1007:1022 The polar lipids of this strain 1007:1037 The polar lipids of this strain consisted of phosphatidylglycerol, diphosphatidylglycerol, phosphatidylinositol, one unknown phospholipid, three unknown glycolipids and two unknown lipids. 26961584 1 30 theme Thermosporothrix 165:180 arg1 soil 122:125 geothermal soil 111:125 geothermal soil 111:125 nov., belonging to the class Ktedonobacteria, isolated from fallen leaves on geothermal soil, and emended description of the genus Thermosporothrix. 26961584 1 30 theme Thermosporothrix 165:180 arg1 description 140:150 emended description 132:150 emended description 132:150 nov., belonging to the class Ktedonobacteria, isolated from fallen leaves on geothermal soil, and emended description of the genus Thermosporothrix. 26961584 0 31 theme Thermosporothrix 0:15 arg1 sp 30:31 Thermosporothrix narukonensis sp 0:31 Thermosporothrix narukonensis sp. 0:32 Thermosporothrix narukonensis sp. 26961584 7 32 theme fatty 806:810 arg1 acid 812:815 The major fatty acid 796:815 The major fatty acid 796:815 The major fatty acid was iso-C17 : 0 and the major menaquinone was MK-9 (H2). 26961584 11 33 theme 98.7  1435:1439 arg1 % 1440:1440 % 1440:1440 % 1440:1440 Detailed phylogenetic analysis based on 16S rRNA gene sequences indicated that strain F4T belongs to the genus Thermosporothrix, and that it was related most closely to Thermosporothrix hazakensis SK20-1T (98.7 % similarity). 26961584 3 34 theme optimum 419:425 arg1 temperature 434:444 optimum growth temperature 419:444 optimum growth temperature 419:444 This strain, designated F4T, grew at temperatures between 30 and 60 °C; optimum growth temperature was 50 °C, whereas no growth was observed below 28 °C or above 65 °C. 26961584 11 35 theme hazakensis 1415:1424 arg1 SK20-1T 1426:1432 Thermosporothrix hazakensis SK20-1T 1398:1432 Thermosporothrix hazakensis SK20-1T (98.7 % similarity) 1398:1452 Detailed phylogenetic analysis based on 16S rRNA gene sequences indicated that strain F4T belongs to the genus Thermosporothrix, and that it was related most closely to Thermosporothrix hazakensis SK20-1T (98.7 % similarity). 26961584 11 35 theme hazakensis 1415:1424 arg1 similarity 1442:1451 98.7 % similarity 1435:1451 98.7 % similarity 1435:1451 Detailed phylogenetic analysis based on 16S rRNA gene sequences indicated that strain F4T belongs to the genus Thermosporothrix, and that it was related most closely to Thermosporothrix hazakensis SK20-1T (98.7 % similarity). 26961584 15 36 theme =NBRC 1754:1758 arg1 29329T 1777:1782 =NBRC 111777T=BCCM/LMG 29329T 1754:1782 =NBRC 111777T=BCCM/LMG 29329T 1754:1782 The type strain is F4T(=NBRC 111777T=BCCM/LMG 29329T). 26961584 15 36 theme =NBRC 1754:1758 arg1 F4T 1750:1752 F4T 1750:1752 F4T(=NBRC 111777T=BCCM/LMG 29329T) 1750:1783 The type strain is F4T(=NBRC 111777T=BCCM/LMG 29329T). 26961584 12 37 theme relatedness 1484:1494 arg1 values 1496:1501 relatedness values 1484:1501 relatedness values of less than 15 % 1484:1519 DNA-DNA hybridization showed relatedness values of less than 15 % with the type strain of Thermosporothrix hazakensis. 26961584 6 38 theme strain 770:775 arg1 F4T 777:779 strain F4T 770:779 strain F4T 770:779 The G+C content in the DNA of strain F4T was 52.5 mol%. 26961584 13 39 theme Thermosporothrix 1692:1707 arg1 species 1683:1689 a novel species 1675:1689 a novel species 1675:1689 On the basis of phenotypic features and phylogenetic position, strain F4T is considered to represent a novel species, Thermosporothrix narukonensis sp. 26961584 13 39 theme Thermosporothrix 1692:1707 arg1 sp 1722:1723 Thermosporothrix narukonensis sp 1692:1723 Thermosporothrix narukonensis sp 1692:1723 On the basis of phenotypic features and phylogenetic position, strain F4T is considered to represent a novel species, Thermosporothrix narukonensis sp. 26961584 15 40 theme type 1735:1738 arg1 strain 1740:1745 The type strain 1731:1745 The type strain 1731:1745 The type strain is F4T(=NBRC 111777T=BCCM/LMG 29329T). 26961584 15 40 theme type 1735:1738 arg1 F4T 1750:1752 F4T 1750:1752 F4T(=NBRC 111777T=BCCM/LMG 29329T) 1750:1783 The type strain is F4T(=NBRC 111777T=BCCM/LMG 29329T). 26961584 13 41 theme novel 1677:1681 arg1 species 1683:1689 a novel species 1675:1689 a novel species 1675:1689 On the basis of phenotypic features and phylogenetic position, strain F4T is considered to represent a novel species, Thermosporothrix narukonensis sp. 26961584 13 41 theme novel 1677:1681 arg1 sp 1722:1723 Thermosporothrix narukonensis sp 1692:1723 Thermosporothrix narukonensis sp 1692:1723 On the basis of phenotypic features and phylogenetic position, strain F4T is considered to represent a novel species, Thermosporothrix narukonensis sp. 26961584 13 42 theme narukonensis 1709:1720 arg1 species 1683:1689 a novel species 1675:1689 a novel species 1675:1689 On the basis of phenotypic features and phylogenetic position, strain F4T is considered to represent a novel species, Thermosporothrix narukonensis sp. 26961584 13 42 theme narukonensis 1709:1720 arg1 sp 1722:1723 Thermosporothrix narukonensis sp 1692:1723 Thermosporothrix narukonensis sp 1692:1723 On the basis of phenotypic features and phylogenetic position, strain F4T is considered to represent a novel species, Thermosporothrix narukonensis sp. 26961584 8 43 contain contained 902:910 arg2 acid 921:924 glutamic acid 912:924 glutamic acid 912:924 The cell wall of strain F4T contained glutamic acid, serine, glycine, alanine and ornithine in a molar ratio of 1.0:1.5:1.4:1.8:0.7. 26961584 8 43 contain contained 902:910 arg2 serine 927:932 serine 927:932 serine 927:932 The cell wall of strain F4T contained glutamic acid, serine, glycine, alanine and ornithine in a molar ratio of 1.0:1.5:1.4:1.8:0.7. 26961584 8 43 contain contained 902:910 arg1 wall 883:886 The cell wall 874:886 The cell wall of strain F4T 874:900 The cell wall of strain F4T contained glutamic acid, serine, glycine, alanine and ornithine in a molar ratio of 1.0:1.5:1.4:1.8:0.7. 26961584 8 43 contain contained 902:910 arg2 ornithine 956:964 ornithine 956:964 ornithine 956:964 The cell wall of strain F4T contained glutamic acid, serine, glycine, alanine and ornithine in a molar ratio of 1.0:1.5:1.4:1.8:0.7. 26961584 8 43 contain contained 902:910 arg2 glycine 935:941 glycine 935:941 glycine 935:941 The cell wall of strain F4T contained glutamic acid, serine, glycine, alanine and ornithine in a molar ratio of 1.0:1.5:1.4:1.8:0.7. 26961584 8 43 contain contained 902:910 arg2 alanine 944:950 alanine 944:950 alanine 944:950 The cell wall of strain F4T contained glutamic acid, serine, glycine, alanine and ornithine in a molar ratio of 1.0:1.5:1.4:1.8:0.7. 26961584 5 44 theme Strain 646:651 arg1 F4T 653:655 Strain F4T 646:655 Strain F4T 646:655 Strain F4T was able to hydrolyse polysaccharides such as cellulose, xylan, chitin and starch. 26961584 4 45 located observed 606:613 arg1 pH 618:619 pH 618:619 pH below 4.4 or above 10.0 618:643 The pH range for growth was 4.9-9.5; the pH for optimum growth was 7.0, but no growth was observed at pH below 4.4 or above 10.0. 26961584 4 45 located observed 606:613 arg2 growth 595:600 no growth 592:600 no growth 592:600 The pH range for growth was 4.9-9.5; the pH for optimum growth was 7.0, but no growth was observed at pH below 4.4 or above 10.0. 26961584 10 46 theme cell-wall 1200:1208 arg1 mannose 1220:1226 mannose 1220:1226 mannose 1220:1226 The cell-wall sugar was mannose. 26961584 10 46 theme cell-wall 1200:1208 arg1 sugar 1210:1214 The cell-wall sugar 1196:1214 The cell-wall sugar 1196:1214 The cell-wall sugar was mannose. 26961584 11 47 theme 16S 1269:1271 arg1 sequences 1283:1291 16S rRNA gene sequences 1269:1291 16S rRNA gene sequences 1269:1291 Detailed phylogenetic analysis based on 16S rRNA gene sequences indicated that strain F4T belongs to the genus Thermosporothrix, and that it was related most closely to Thermosporothrix hazakensis SK20-1T (98.7 % similarity). 26961584 13 48 theme phenotypic 1590:1599 arg1 features 1601:1608 phenotypic features 1590:1608 phenotypic features 1590:1608 On the basis of phenotypic features and phylogenetic position, strain F4T is considered to represent a novel species, Thermosporothrix narukonensis sp. 26961584 1 49 attach isolated 80:87 arg1 fallen 94:99 fallen 94:99 fallen 94:99 nov., belonging to the class Ktedonobacteria, isolated from fallen leaves on geothermal soil, and emended description of the genus Thermosporothrix. 26961584 1 49 attach isolated 80:87 arg2 nov. 34:37 nov. 34:37 nov. 34:37 nov., belonging to the class Ktedonobacteria, isolated from fallen leaves on geothermal soil, and emended description of the genus Thermosporothrix. 26961584 4 50 dep 4.9-9.5 544:550 arg1 7.0 583:585 7.0 583:585 7.0 583:585 The pH range for growth was 4.9-9.5; the pH for optimum growth was 7.0, but no growth was observed at pH below 4.4 or above 10.0. 26961584 4 50 dep 4.9-9.5 544:550 arg1 pH 557:558 the pH 553:558 the pH for optimum growth 553:577 The pH range for growth was 4.9-9.5; the pH for optimum growth was 7.0, but no growth was observed at pH below 4.4 or above 10.0. 26961584 4 50 dep 4.9-9.5 544:550 arg1 observed 606:613 observed 606:613 was observed at pH below 4.4 or above 10.0 602:643 The pH range for growth was 4.9-9.5; the pH for optimum growth was 7.0, but no growth was observed at pH below 4.4 or above 10.0. 26961584 2 51 dep fallen 313:318 arg1 leaves 320:325 leaves 320:325 leaves on geothermal soil 320:344 A thermophilic, Gram-stain-positive, spore-forming bacterium that formed branched vegetative and aerial mycelia was isolated from fallen leaves on geothermal soil. 26961584 6 52 from content 748:754 arg1 DNA 763:765 the DNA 759:765 the DNA of strain F4T 759:779 The G+C content in the DNA of strain F4T was 52.5 mol%. 26961584 4 53 theme pH 520:521 arg1 4.9-9.5 544:550 4.9-9.5 544:550 4.9-9.5 544:550 The pH range for growth was 4.9-9.5; the pH for optimum growth was 7.0, but no growth was observed at pH below 4.4 or above 10.0. 26961584 4 53 theme pH 520:521 arg1 range 523:527 The pH range 516:527 The pH range for growth 516:538 The pH range for growth was 4.9-9.5; the pH for optimum growth was 7.0, but no growth was observed at pH below 4.4 or above 10.0. 26961584 15 54 theme 111777T=BCCM/LMG 1760:1775 arg1 29329T 1777:1782 =NBRC 111777T=BCCM/LMG 29329T 1754:1782 =NBRC 111777T=BCCM/LMG 29329T 1754:1782 The type strain is F4T(=NBRC 111777T=BCCM/LMG 29329T). 26961584 15 54 theme 111777T=BCCM/LMG 1760:1775 arg1 F4T 1750:1752 F4T 1750:1752 F4T(=NBRC 111777T=BCCM/LMG 29329T) 1750:1783 The type strain is F4T(=NBRC 111777T=BCCM/LMG 29329T). 26961584 1 55 theme emended 132:138 arg1 description 140:150 emended description 132:150 emended description 132:150 nov., belonging to the class Ktedonobacteria, isolated from fallen leaves on geothermal soil, and emended description of the genus Thermosporothrix. 26961584 11 56 theme % 1440:1440 arg1 SK20-1T 1426:1432 Thermosporothrix hazakensis SK20-1T 1398:1432 Thermosporothrix hazakensis SK20-1T (98.7 % similarity) 1398:1452 Detailed phylogenetic analysis based on 16S rRNA gene sequences indicated that strain F4T belongs to the genus Thermosporothrix, and that it was related most closely to Thermosporothrix hazakensis SK20-1T (98.7 % similarity). 26961584 11 56 theme % 1440:1440 arg1 similarity 1442:1451 98.7 % similarity 1435:1451 98.7 % similarity 1435:1451 Detailed phylogenetic analysis based on 16S rRNA gene sequences indicated that strain F4T belongs to the genus Thermosporothrix, and that it was related most closely to Thermosporothrix hazakensis SK20-1T (98.7 % similarity). 26961584 1 57 theme geothermal 111:120 arg1 soil 122:125 geothermal soil 111:125 geothermal soil 111:125 nov., belonging to the class Ktedonobacteria, isolated from fallen leaves on geothermal soil, and emended description of the genus Thermosporothrix. 26961584 13 58 theme strain 1637:1642 arg1 F4T 1644:1646 strain F4T 1637:1646 strain F4T 1637:1646 On the basis of phenotypic features and phylogenetic position, strain F4T is considered to represent a novel species, Thermosporothrix narukonensis sp. 26961584 13 59 theme phylogenetic 1614:1625 arg1 position 1627:1634 phylogenetic position 1614:1634 phylogenetic position 1614:1634 On the basis of phenotypic features and phylogenetic position, strain F4T is considered to represent a novel species, Thermosporothrix narukonensis sp. 26961584 11 60 theme Thermosporothrix 1398:1413 arg1 SK20-1T 1426:1432 Thermosporothrix hazakensis SK20-1T 1398:1432 Thermosporothrix hazakensis SK20-1T (98.7 % similarity) 1398:1452 Detailed phylogenetic analysis based on 16S rRNA gene sequences indicated that strain F4T belongs to the genus Thermosporothrix, and that it was related most closely to Thermosporothrix hazakensis SK20-1T (98.7 % similarity). 26961584 11 60 theme Thermosporothrix 1398:1413 arg1 similarity 1442:1451 98.7 % similarity 1435:1451 98.7 % similarity 1435:1451 Detailed phylogenetic analysis based on 16S rRNA gene sequences indicated that strain F4T belongs to the genus Thermosporothrix, and that it was related most closely to Thermosporothrix hazakensis SK20-1T (98.7 % similarity). 26961584 7 61 theme major 800:804 arg1 acid 812:815 The major fatty acid 796:815 The major fatty acid 796:815 The major fatty acid was iso-C17 : 0 and the major menaquinone was MK-9 (H2). 26961584 2 62 dep thermophilic 185:196 arg1 spore-forming 220:232 spore-forming 220:232 spore-forming 220:232 A thermophilic, Gram-stain-positive, spore-forming bacterium that formed branched vegetative and aerial mycelia was isolated from fallen leaves on geothermal soil. 26961584 2 62 dep thermophilic 185:196 arg1 Gram-stain-positive 199:217 Gram-stain-positive 199:217 Gram-stain-positive 199:217 A thermophilic, Gram-stain-positive, spore-forming bacterium that formed branched vegetative and aerial mycelia was isolated from fallen leaves on geothermal soil. 26961584 2 63 theme thermophilic 185:196 arg1 bacterium 234:242 A thermophilic, Gram-stain-positive, spore-forming bacterium 183:242 A thermophilic, Gram-stain-positive, spore-forming bacterium that formed branched vegetative and aerial mycelia 183:293 A thermophilic, Gram-stain-positive, spore-forming bacterium that formed branched vegetative and aerial mycelia was isolated from fallen leaves on geothermal soil. 26961584 2 64 theme vegetative 265:274 arg1 mycelia 287:293 branched vegetative and aerial mycelia 256:293 branched vegetative and aerial mycelia 256:293 A thermophilic, Gram-stain-positive, spore-forming bacterium that formed branched vegetative and aerial mycelia was isolated from fallen leaves on geothermal soil. 26961584 2 65 theme geothermal 330:339 arg1 soil 341:344 geothermal soil 330:344 geothermal soil 330:344 A thermophilic, Gram-stain-positive, spore-forming bacterium that formed branched vegetative and aerial mycelia was isolated from fallen leaves on geothermal soil. 26961584 11 66 theme genus 1334:1338 arg1 Thermosporothrix 1340:1355 the genus Thermosporothrix 1330:1355 the genus Thermosporothrix 1330:1355 Detailed phylogenetic analysis based on 16S rRNA gene sequences indicated that strain F4T belongs to the genus Thermosporothrix, and that it was related most closely to Thermosporothrix hazakensis SK20-1T (98.7 % similarity). 26961584 8 67 from serine 927:932 arg1 ratio 977:981 a molar ratio 969:981 a molar ratio of 1.0:1.5:1.4:1.8:0.7 969:1004 The cell wall of strain F4T contained glutamic acid, serine, glycine, alanine and ornithine in a molar ratio of 1.0:1.5:1.4:1.8:0.7. 26961584 13 68 dep features 1601:1608 arg1 basis 1581:1585 basis 1581:1585 basis 1581:1585 On the basis of phenotypic features and phylogenetic position, strain F4T is considered to represent a novel species, Thermosporothrix narukonensis sp. 26961584 13 68 dep features 1601:1608 arg1 the 1577:1579 the 1577:1579 the 1577:1579 On the basis of phenotypic features and phylogenetic position, strain F4T is considered to represent a novel species, Thermosporothrix narukonensis sp. 26961584 9 69 theme unknown 1124:1130 arg1 phospholipid 1132:1143 one unknown phospholipid 1120:1143 one unknown phospholipid 1120:1143 The polar lipids of this strain consisted of phosphatidylglycerol, diphosphatidylglycerol, phosphatidylinositol, one unknown phospholipid, three unknown glycolipids and two unknown lipids. 26961584 2 70 theme branched 256:263 arg1 mycelia 287:293 branched vegetative and aerial mycelia 256:293 branched vegetative and aerial mycelia 256:293 A thermophilic, Gram-stain-positive, spore-forming bacterium that formed branched vegetative and aerial mycelia was isolated from fallen leaves on geothermal soil. 26961584 12 71 theme hazakensis 1562:1571 arg1 strain 1535:1540 the type strain 1526:1540 the type strain of Thermosporothrix hazakensis 1526:1571 DNA-DNA hybridization showed relatedness values of less than 15 % with the type strain of Thermosporothrix hazakensis. 26961584 8 72 from acid 921:924 arg1 ratio 977:981 a molar ratio 969:981 a molar ratio of 1.0:1.5:1.4:1.8:0.7 969:1004 The cell wall of strain F4T contained glutamic acid, serine, glycine, alanine and ornithine in a molar ratio of 1.0:1.5:1.4:1.8:0.7. 26961584 7 73 theme major 841:845 arg1 MK-9 863:866 MK-9 863:866 MK-9 863:866 The major fatty acid was iso-C17 : 0 and the major menaquinone was MK-9 (H2). 26961584 7 73 theme major 841:845 arg1 menaquinone 847:857 the major menaquinone 837:857 the major menaquinone 837:857 The major fatty acid was iso-C17 : 0 and the major menaquinone was MK-9 (H2). 26961584 4 74 theme optimum 564:570 arg1 growth 572:577 optimum growth 564:577 optimum growth 564:577 The pH range for growth was 4.9-9.5; the pH for optimum growth was 7.0, but no growth was observed at pH below 4.4 or above 10.0. 26961584 2 75 attach isolated 299:306 arg1 fallen 313:318 fallen 313:318 fallen 313:318 A thermophilic, Gram-stain-positive, spore-forming bacterium that formed branched vegetative and aerial mycelia was isolated from fallen leaves on geothermal soil. 26961584 2 75 attach isolated 299:306 arg2 bacterium 234:242 A thermophilic, Gram-stain-positive, spore-forming bacterium 183:242 A thermophilic, Gram-stain-positive, spore-forming bacterium that formed branched vegetative and aerial mycelia 183:293 A thermophilic, Gram-stain-positive, spore-forming bacterium that formed branched vegetative and aerial mycelia was isolated from fallen leaves on geothermal soil. 24414342 8 0 theme terminal 1133:1140 arg1 T-RFLP 1184:1189 T-RFLP 1184:1189 T-RFLP 1184:1189 Diversity and community structure were analysed by terminal restriction fragment length polymorphism (T-RFLP) patterns, and principal component analysis was utilized on immunological and T-RFLP patterns. 24414342 8 0 theme terminal 1133:1140 arg1 polymorphism 1170:1181 terminal restriction fragment length polymorphism 1133:1181 terminal restriction fragment length polymorphism (T-RFLP) patterns 1133:1199 Diversity and community structure were analysed by terminal restriction fragment length polymorphism (T-RFLP) patterns, and principal component analysis was utilized on immunological and T-RFLP patterns. 24414342 9 1 theme DSS-induced 1286:1296 arg1 colitis 1298:1304 DSS-induced colitis 1286:1304 DSS-induced colitis 1286:1304 DSS-induced colitis show clinical and histological similarities to UC. 24414342 10 2 theme system 1476:1481 arg1 alterations 1450:1460 several alterations 1442:1460 several alterations of the immune system 1442:1481 The composition of the colonic microflora was profoundly changed and correlated with several alterations of the immune system. 24414342 7 3 theme total 956:960 arg1 amount 962:967 the total amount 952:967 the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae 894:1034 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 7 3 theme total 956:960 arg1 Desulfovibrio 999:1011 Desulfovibrio 999:1011 Desulfovibrio 999:1011 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 7 3 theme total 956:960 arg1 Enterobacteriaceae 1017:1034 Enterobacteriaceae 1017:1034 Enterobacteriaceae 1017:1034 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 7 3 theme total 956:960 arg1 lactobacilli 972:983 lactobacilli 972:983 lactobacilli 972:983 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 7 3 theme total 956:960 arg1 Akkermansia 986:996 Akkermansia 986:996 Akkermansia 986:996 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 7 3 theme total 956:960 arg1 bacteria 914:921 bacteria 914:921 bacteria on colonic mucosa 914:939 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 0 4 theme sodium 77:82 arg1 administration 90:103 dextran sulfate sodium (DSS) administration 61:103 dextran sulfate sodium (DSS) administration in mice 61:111 Immunological alteration and changes of gut microbiota after dextran sulfate sodium (DSS) administration in mice. 24414342 10 5 theme colonic 1380:1386 arg1 microflora 1388:1397 the colonic microflora 1376:1397 the colonic microflora 1376:1397 The composition of the colonic microflora was profoundly changed and correlated with several alterations of the immune system. 24414342 6 6 theme mesenteric 798:807 arg1 nodes 815:819 mesenteric lymph nodes 798:819 mesenteric lymph nodes 798:819 Immunological changes were assessed by flow cytometry in spleen, Peyer's patches and mesenteric lymph nodes and through multiplex cytokine profiling. 24414342 11 7 theme multiple 1531:1538 arg1 changes 1554:1560 multiple immunological changes 1531:1560 multiple immunological changes 1531:1560 The results demonstrate a relationship between multiple immunological changes and alterations of the gut microbiota after DSS administration. 24414342 10 8 theme immune 1469:1474 arg1 system 1476:1481 the immune system 1465:1481 the immune system 1465:1481 The composition of the colonic microflora was profoundly changed and correlated with several alterations of the immune system. 24414342 8 9 theme fragment 1154:1161 arg1 T-RFLP 1184:1189 T-RFLP 1184:1189 T-RFLP 1184:1189 Diversity and community structure were analysed by terminal restriction fragment length polymorphism (T-RFLP) patterns, and principal component analysis was utilized on immunological and T-RFLP patterns. 24414342 8 9 theme fragment 1154:1161 arg1 polymorphism 1170:1181 terminal restriction fragment length polymorphism 1133:1181 terminal restriction fragment length polymorphism (T-RFLP) patterns 1133:1199 Diversity and community structure were analysed by terminal restriction fragment length polymorphism (T-RFLP) patterns, and principal component analysis was utilized on immunological and T-RFLP patterns. 24414342 7 10 theme colonic 926:932 arg1 mucosa 934:939 colonic mucosa 926:939 colonic mucosa 926:939 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 5 11 theme Intestinal 614:623 arg1 inflammation 625:636 Intestinal inflammation 614:636 Intestinal inflammation 614:636 Intestinal inflammation was verified through histological evaluation and myeloperoxidase activity. 24414342 8 12 theme principal 1206:1214 arg1 analysis 1226:1233 principal component analysis 1206:1233 principal component analysis 1206:1233 Diversity and community structure were analysed by terminal restriction fragment length polymorphism (T-RFLP) patterns, and principal component analysis was utilized on immunological and T-RFLP patterns. 24414342 8 13 used utilized 1239:1246 arg2 analysis 1226:1233 principal component analysis 1206:1233 principal component analysis 1206:1233 Diversity and community structure were analysed by terminal restriction fragment length polymorphism (T-RFLP) patterns, and principal component analysis was utilized on immunological and T-RFLP patterns. 24414342 11 14 theme immunological 1540:1552 arg1 changes 1554:1560 multiple immunological changes 1531:1560 multiple immunological changes 1531:1560 The results demonstrate a relationship between multiple immunological changes and alterations of the gut microbiota after DSS administration. 24414342 4 15 theme DSS 561:563 arg1 effect 551:556 the effect 547:556 the effect of DSS on the immune system and gut microbiota in mice 547:611 To enlarge the understanding of the pathogenesis, we have studied the effect of DSS on the immune system and gut microbiota in mice. 24414342 8 16 theme restriction 1142:1152 arg1 T-RFLP 1184:1189 T-RFLP 1184:1189 T-RFLP 1184:1189 Diversity and community structure were analysed by terminal restriction fragment length polymorphism (T-RFLP) patterns, and principal component analysis was utilized on immunological and T-RFLP patterns. 24414342 8 16 theme restriction 1142:1152 arg1 polymorphism 1170:1181 terminal restriction fragment length polymorphism 1133:1181 terminal restriction fragment length polymorphism (T-RFLP) patterns 1133:1199 Diversity and community structure were analysed by terminal restriction fragment length polymorphism (T-RFLP) patterns, and principal component analysis was utilized on immunological and T-RFLP patterns. 24414342 9 17 theme clinical 1311:1318 arg1 similarities 1337:1348 clinical and histological similarities 1311:1348 clinical and histological similarities to UC 1311:1354 DSS-induced colitis show clinical and histological similarities to UC. 24414342 12 18 theme gut 1760:1762 arg1 microbiota 1764:1773 the gut microbiota 1756:1773 the gut microbiota 1756:1773 These data highlight and improve the definition of the immunological basis of the disease and suggest a role for dysregulation of the gut microbiota in the pathogenesis of colitis. 24414342 11 19 theme DSS 1606:1608 arg1 administration 1610:1623 DSS administration 1606:1623 DSS administration 1606:1623 The results demonstrate a relationship between multiple immunological changes and alterations of the gut microbiota after DSS administration. 24414342 4 20 from effect 551:556 arg1 microbiota 594:603 gut microbiota 590:603 gut microbiota in mice 590:611 To enlarge the understanding of the pathogenesis, we have studied the effect of DSS on the immune system and gut microbiota in mice. 24414342 4 20 from effect 551:556 arg1 system 579:584 the immune system 568:584 the immune system 568:584 To enlarge the understanding of the pathogenesis, we have studied the effect of DSS on the immune system and gut microbiota in mice. 24414342 7 21 theme PCR 1077:1079 arg1 use 1057:1059 the use 1053:1059 the use of quantitative PCR 1053:1079 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 10 22 theme microflora 1388:1397 arg1 composition 1361:1371 The composition 1357:1371 The composition of the colonic microflora 1357:1397 The composition of the colonic microflora was profoundly changed and correlated with several alterations of the immune system. 24414342 7 23 from amount 962:967 arg1 mucosa 934:939 colonic mucosa 926:939 colonic mucosa 926:939 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 8 24 theme length 1163:1168 arg1 T-RFLP 1184:1189 T-RFLP 1184:1189 T-RFLP 1184:1189 Diversity and community structure were analysed by terminal restriction fragment length polymorphism (T-RFLP) patterns, and principal component analysis was utilized on immunological and T-RFLP patterns. 24414342 8 24 theme length 1163:1168 arg1 polymorphism 1170:1181 terminal restriction fragment length polymorphism 1133:1181 terminal restriction fragment length polymorphism (T-RFLP) patterns 1133:1199 Diversity and community structure were analysed by terminal restriction fragment length polymorphism (T-RFLP) patterns, and principal component analysis was utilized on immunological and T-RFLP patterns. 24414342 9 25 theme histological 1324:1335 arg1 similarities 1337:1348 clinical and histological similarities 1311:1348 clinical and histological similarities to UC 1311:1354 DSS-induced colitis show clinical and histological similarities to UC. 24414342 10 26 theme several 1442:1448 arg1 alterations 1450:1460 several alterations 1442:1460 several alterations of the immune system 1442:1481 The composition of the colonic microflora was profoundly changed and correlated with several alterations of the immune system. 24414342 12 27 theme colitis 1798:1804 arg1 pathogenesis 1782:1793 the pathogenesis 1778:1793 the pathogenesis of colitis 1778:1804 These data highlight and improve the definition of the immunological basis of the disease and suggest a role for dysregulation of the gut microbiota in the pathogenesis of colitis. 24414342 3 28 theme increased 397:405 arg1 permeability 418:429 increased intestinal permeability 397:429 increased intestinal permeability 397:429 Deregulation of the immune response to the enteric microflora or pathogens as well as increased intestinal permeability have been proposed as disease-driving mechanisms. 24414342 4 29 from system 579:584 arg1 mice 608:611 mice 608:611 mice 608:611 To enlarge the understanding of the pathogenesis, we have studied the effect of DSS on the immune system and gut microbiota in mice. 24414342 12 30 theme disease 1708:1714 arg1 basis 1695:1699 the immunological basis 1677:1699 the immunological basis of the disease 1677:1714 These data highlight and improve the definition of the immunological basis of the disease and suggest a role for dysregulation of the gut microbiota in the pathogenesis of colitis. 24414342 1 31 theme chronic 158:164 arg1 inflammation 166:177 chronic inflammation 158:177 chronic inflammation of the colonic mucosa 158:199 Ulcerative colitis (UC) is characterized by chronic inflammation of the colonic mucosa. 24414342 0 32 theme Immunological 0:12 arg1 alteration 14:23 Immunological alteration 0:23 Immunological alteration 0:23 Immunological alteration and changes of gut microbiota after dextran sulfate sodium (DSS) administration in mice. 24414342 7 33 theme quantitative 1064:1075 arg1 PCR 1077:1079 quantitative PCR 1064:1079 quantitative PCR 1064:1079 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 11 34 theme microbiota 1589:1598 arg1 alterations 1566:1576 alterations 1566:1576 alterations of the gut microbiota after DSS administration 1566:1623 The results demonstrate a relationship between multiple immunological changes and alterations of the gut microbiota after DSS administration. 24414342 11 34 theme microbiota 1589:1598 arg1 changes 1554:1560 multiple immunological changes 1531:1560 multiple immunological changes 1531:1560 The results demonstrate a relationship between multiple immunological changes and alterations of the gut microbiota after DSS administration. 24414342 2 35 theme used 276:279 arg1 Administration 202:215 Administration 202:215 Administration of dextran sulfate sodium (DSS) to animals 202:258 Administration of dextran sulfate sodium (DSS) to animals is a frequently used model to mimic human colitis. 24414342 2 35 theme used 276:279 arg1 model 281:285 a frequently used model 263:285 a frequently used model to mimic human colitis 263:308 Administration of dextran sulfate sodium (DSS) to animals is a frequently used model to mimic human colitis. 24414342 3 36 theme immune 331:336 arg1 response 338:345 the immune response 327:345 the immune response to the enteric microflora or pathogens as well as increased intestinal permeability 327:429 Deregulation of the immune response to the enteric microflora or pathogens as well as increased intestinal permeability have been proposed as disease-driving mechanisms. 24414342 7 37 theme bacteria 914:921 arg1 amount 962:967 the total amount 952:967 the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae 894:1034 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 7 37 theme bacteria 914:921 arg1 Desulfovibrio 999:1011 Desulfovibrio 999:1011 Desulfovibrio 999:1011 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 7 37 theme bacteria 914:921 arg1 amount 904:909 the total amount 894:909 the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae 894:1034 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 7 37 theme bacteria 914:921 arg1 Enterobacteriaceae 1017:1034 Enterobacteriaceae 1017:1034 Enterobacteriaceae 1017:1034 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 7 37 theme bacteria 914:921 arg1 lactobacilli 972:983 lactobacilli 972:983 lactobacilli 972:983 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 7 37 theme bacteria 914:921 arg1 Akkermansia 986:996 Akkermansia 986:996 Akkermansia 986:996 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 7 37 theme bacteria 914:921 arg1 bacteria 914:921 bacteria 914:921 bacteria on colonic mucosa 914:939 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 4 38 from microbiota 594:603 arg1 mice 608:611 mice 608:611 mice 608:611 To enlarge the understanding of the pathogenesis, we have studied the effect of DSS on the immune system and gut microbiota in mice. 24414342 4 39 theme gut 590:592 arg1 microbiota 594:603 gut microbiota 590:603 gut microbiota in mice 590:611 To enlarge the understanding of the pathogenesis, we have studied the effect of DSS on the immune system and gut microbiota in mice. 24414342 3 40 theme response 338:345 arg1 Deregulation 311:322 Deregulation 311:322 Deregulation of the immune response to the enteric microflora or pathogens as well as increased intestinal permeability 311:429 Deregulation of the immune response to the enteric microflora or pathogens as well as increased intestinal permeability have been proposed as disease-driving mechanisms. 24414342 3 40 theme response 338:345 arg1 mechanisms 469:478 disease-driving mechanisms 453:478 disease-driving mechanisms 453:478 Deregulation of the immune response to the enteric microflora or pathogens as well as increased intestinal permeability have been proposed as disease-driving mechanisms. 24414342 7 41 from amount 904:909 arg1 mucosa 934:939 colonic mucosa 926:939 colonic mucosa 926:939 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 12 42 theme basis 1695:1699 arg1 definition 1663:1672 the definition 1659:1672 the definition of the immunological basis of the disease 1659:1714 These data highlight and improve the definition of the immunological basis of the disease and suggest a role for dysregulation of the gut microbiota in the pathogenesis of colitis. 24414342 8 43 theme immunological 1251:1263 arg1 patterns 1276:1283 immunological and T-RFLP patterns 1251:1283 immunological and T-RFLP patterns 1251:1283 Diversity and community structure were analysed by terminal restriction fragment length polymorphism (T-RFLP) patterns, and principal component analysis was utilized on immunological and T-RFLP patterns. 24414342 0 44 theme gut 40:42 arg1 microbiota 44:53 gut microbiota 40:53 gut microbiota 40:53 Immunological alteration and changes of gut microbiota after dextran sulfate sodium (DSS) administration in mice. 24414342 7 45 from bacteria 914:921 arg1 mucosa 934:939 colonic mucosa 926:939 colonic mucosa 926:939 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 5 46 theme myeloperoxidase 687:701 arg1 activity 703:710 myeloperoxidase activity 687:710 myeloperoxidase activity 687:710 Intestinal inflammation was verified through histological evaluation and myeloperoxidase activity. 24414342 1 47 theme colonic 186:192 arg1 mucosa 194:199 the colonic mucosa 182:199 the colonic mucosa 182:199 Ulcerative colitis (UC) is characterized by chronic inflammation of the colonic mucosa. 24414342 2 48 theme dextran 220:226 arg1 sodium 236:241 dextran sulfate sodium 220:241 dextran sulfate sodium (DSS) 220:247 Administration of dextran sulfate sodium (DSS) to animals is a frequently used model to mimic human colitis. 24414342 2 48 theme dextran 220:226 arg1 DSS 244:246 DSS 244:246 DSS 244:246 Administration of dextran sulfate sodium (DSS) to animals is a frequently used model to mimic human colitis. 24414342 12 49 theme immunological 1681:1693 arg1 basis 1695:1699 the immunological basis 1677:1699 the immunological basis of the disease 1677:1714 These data highlight and improve the definition of the immunological basis of the disease and suggest a role for dysregulation of the gut microbiota in the pathogenesis of colitis. 24414342 3 50 theme intestinal 407:416 arg1 permeability 418:429 increased intestinal permeability 397:429 increased intestinal permeability 397:429 Deregulation of the immune response to the enteric microflora or pathogens as well as increased intestinal permeability have been proposed as disease-driving mechanisms. 24414342 6 51 theme cytokine 843:850 arg1 profiling 852:860 multiplex cytokine profiling 833:860 multiplex cytokine profiling 833:860 Immunological changes were assessed by flow cytometry in spleen, Peyer's patches and mesenteric lymph nodes and through multiplex cytokine profiling. 24414342 7 52 theme Akkermansia 986:996 arg1 amount 962:967 the total amount 952:967 the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae 894:1034 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 7 52 theme Akkermansia 986:996 arg1 Desulfovibrio 999:1011 Desulfovibrio 999:1011 Desulfovibrio 999:1011 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 7 52 theme Akkermansia 986:996 arg1 amount 904:909 the total amount 894:909 the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae 894:1034 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 7 52 theme Akkermansia 986:996 arg1 Enterobacteriaceae 1017:1034 Enterobacteriaceae 1017:1034 Enterobacteriaceae 1017:1034 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 7 52 theme Akkermansia 986:996 arg1 lactobacilli 972:983 lactobacilli 972:983 lactobacilli 972:983 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 7 52 theme Akkermansia 986:996 arg1 Akkermansia 986:996 Akkermansia 986:996 Akkermansia 986:996 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 7 52 theme Akkermansia 986:996 arg1 bacteria 914:921 bacteria 914:921 bacteria on colonic mucosa 914:939 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 1 53 theme mucosa 194:199 arg1 inflammation 166:177 chronic inflammation 158:177 chronic inflammation of the colonic mucosa 158:199 Ulcerative colitis (UC) is characterized by chronic inflammation of the colonic mucosa. 24414342 3 54 theme enteric 354:360 arg1 microflora 362:371 the enteric microflora 350:371 the enteric microflora 350:371 Deregulation of the immune response to the enteric microflora or pathogens as well as increased intestinal permeability have been proposed as disease-driving mechanisms. 24414342 7 55 theme Enterobacteriaceae 1017:1034 arg1 amount 962:967 the total amount 952:967 the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae 894:1034 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 7 55 theme Enterobacteriaceae 1017:1034 arg1 Desulfovibrio 999:1011 Desulfovibrio 999:1011 Desulfovibrio 999:1011 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 7 55 theme Enterobacteriaceae 1017:1034 arg1 amount 904:909 the total amount 894:909 the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae 894:1034 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 7 55 theme Enterobacteriaceae 1017:1034 arg1 Enterobacteriaceae 1017:1034 Enterobacteriaceae 1017:1034 Enterobacteriaceae 1017:1034 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 7 55 theme Enterobacteriaceae 1017:1034 arg1 lactobacilli 972:983 lactobacilli 972:983 lactobacilli 972:983 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 7 55 theme Enterobacteriaceae 1017:1034 arg1 Akkermansia 986:996 Akkermansia 986:996 Akkermansia 986:996 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 7 55 theme Enterobacteriaceae 1017:1034 arg1 bacteria 914:921 bacteria 914:921 bacteria on colonic mucosa 914:939 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 6 56 theme multiplex 833:841 arg1 profiling 852:860 multiplex cytokine profiling 833:860 multiplex cytokine profiling 833:860 Immunological changes were assessed by flow cytometry in spleen, Peyer's patches and mesenteric lymph nodes and through multiplex cytokine profiling. 24414342 6 57 theme flow 752:755 arg1 cytometry 757:765 flow cytometry 752:765 flow cytometry 752:765 Immunological changes were assessed by flow cytometry in spleen, Peyer's patches and mesenteric lymph nodes and through multiplex cytokine profiling. 24414342 3 58 theme disease-driving 453:467 arg1 Deregulation 311:322 Deregulation 311:322 Deregulation of the immune response to the enteric microflora or pathogens as well as increased intestinal permeability 311:429 Deregulation of the immune response to the enteric microflora or pathogens as well as increased intestinal permeability have been proposed as disease-driving mechanisms. 24414342 3 58 theme disease-driving 453:467 arg1 mechanisms 469:478 disease-driving mechanisms 453:478 disease-driving mechanisms 453:478 Deregulation of the immune response to the enteric microflora or pathogens as well as increased intestinal permeability have been proposed as disease-driving mechanisms. 24414342 0 59 theme microbiota 44:53 arg1 changes 29:35 changes 29:35 changes 29:35 Immunological alteration and changes of gut microbiota after dextran sulfate sodium (DSS) administration in mice. 24414342 0 59 theme microbiota 44:53 arg1 alteration 14:23 Immunological alteration 0:23 Immunological alteration 0:23 Immunological alteration and changes of gut microbiota after dextran sulfate sodium (DSS) administration in mice. 24414342 4 60 theme pathogenesis 517:528 arg1 understanding 496:508 the understanding 492:508 the understanding of the pathogenesis 492:528 To enlarge the understanding of the pathogenesis, we have studied the effect of DSS on the immune system and gut microbiota in mice. 24414342 12 61 theme microbiota 1764:1773 arg1 dysregulation 1739:1751 dysregulation 1739:1751 dysregulation of the gut microbiota 1739:1773 These data highlight and improve the definition of the immunological basis of the disease and suggest a role for dysregulation of the gut microbiota in the pathogenesis of colitis. 24414342 11 62 theme gut 1585:1587 arg1 microbiota 1589:1598 the gut microbiota 1581:1598 the gut microbiota after DSS administration 1581:1623 The results demonstrate a relationship between multiple immunological changes and alterations of the gut microbiota after DSS administration. 24414342 7 63 theme lactobacilli 972:983 arg1 amount 962:967 the total amount 952:967 the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae 894:1034 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 7 63 theme lactobacilli 972:983 arg1 Desulfovibrio 999:1011 Desulfovibrio 999:1011 Desulfovibrio 999:1011 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 7 63 theme lactobacilli 972:983 arg1 amount 904:909 the total amount 894:909 the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae 894:1034 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 7 63 theme lactobacilli 972:983 arg1 Enterobacteriaceae 1017:1034 Enterobacteriaceae 1017:1034 Enterobacteriaceae 1017:1034 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 7 63 theme lactobacilli 972:983 arg1 lactobacilli 972:983 lactobacilli 972:983 lactobacilli 972:983 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 7 63 theme lactobacilli 972:983 arg1 Akkermansia 986:996 Akkermansia 986:996 Akkermansia 986:996 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 7 63 theme lactobacilli 972:983 arg1 bacteria 914:921 bacteria 914:921 bacteria on colonic mucosa 914:939 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 2 64 theme human 296:300 arg1 colitis 302:308 human colitis 296:308 human colitis 296:308 Administration of dextran sulfate sodium (DSS) to animals is a frequently used model to mimic human colitis. 24414342 7 65 theme total 898:902 arg1 Desulfovibrio 999:1011 Desulfovibrio 999:1011 Desulfovibrio 999:1011 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 7 65 theme total 898:902 arg1 amount 904:909 the total amount 894:909 the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae 894:1034 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 7 65 theme total 898:902 arg1 Enterobacteriaceae 1017:1034 Enterobacteriaceae 1017:1034 Enterobacteriaceae 1017:1034 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 7 65 theme total 898:902 arg1 lactobacilli 972:983 lactobacilli 972:983 lactobacilli 972:983 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 7 65 theme total 898:902 arg1 Akkermansia 986:996 Akkermansia 986:996 Akkermansia 986:996 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 7 65 theme total 898:902 arg1 bacteria 914:921 bacteria 914:921 bacteria on colonic mucosa 914:939 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 7 66 theme Desulfovibrio 999:1011 arg1 amount 962:967 the total amount 952:967 the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae 894:1034 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 7 66 theme Desulfovibrio 999:1011 arg1 Desulfovibrio 999:1011 Desulfovibrio 999:1011 Desulfovibrio 999:1011 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 7 66 theme Desulfovibrio 999:1011 arg1 amount 904:909 the total amount 894:909 the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae 894:1034 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 7 66 theme Desulfovibrio 999:1011 arg1 Enterobacteriaceae 1017:1034 Enterobacteriaceae 1017:1034 Enterobacteriaceae 1017:1034 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 7 66 theme Desulfovibrio 999:1011 arg1 lactobacilli 972:983 lactobacilli 972:983 lactobacilli 972:983 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 7 66 theme Desulfovibrio 999:1011 arg1 Akkermansia 986:996 Akkermansia 986:996 Akkermansia 986:996 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 7 66 theme Desulfovibrio 999:1011 arg1 bacteria 914:921 bacteria 914:921 bacteria on colonic mucosa 914:939 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 0 67 from administration 90:103 arg1 mice 108:111 mice 108:111 mice 108:111 Immunological alteration and changes of gut microbiota after dextran sulfate sodium (DSS) administration in mice. 24414342 8 68 theme community 1096:1104 arg1 structure 1106:1114 community structure 1096:1114 community structure 1096:1114 Diversity and community structure were analysed by terminal restriction fragment length polymorphism (T-RFLP) patterns, and principal component analysis was utilized on immunological and T-RFLP patterns. 24414342 1 69 theme Ulcerative 114:123 arg1 UC 134:135 UC 134:135 UC 134:135 Ulcerative colitis (UC) is characterized by chronic inflammation of the colonic mucosa. 24414342 1 69 theme Ulcerative 114:123 arg1 colitis 125:131 Ulcerative colitis 114:131 Ulcerative colitis (UC) 114:136 Ulcerative colitis (UC) is characterized by chronic inflammation of the colonic mucosa. 24414342 7 70 theme amount 904:909 arg1 quantification 876:889 quantification 876:889 quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae 876:1034 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 8 71 theme T-RFLP 1269:1274 arg1 patterns 1276:1283 immunological and T-RFLP patterns 1251:1283 immunological and T-RFLP patterns 1251:1283 Diversity and community structure were analysed by terminal restriction fragment length polymorphism (T-RFLP) patterns, and principal component analysis was utilized on immunological and T-RFLP patterns. 24414342 5 72 theme histological 659:670 arg1 evaluation 672:681 histological evaluation 659:681 histological evaluation 659:681 Intestinal inflammation was verified through histological evaluation and myeloperoxidase activity. 24414342 12 73 from role 1730:1733 arg1 pathogenesis 1782:1793 the pathogenesis 1778:1793 the pathogenesis of colitis 1778:1804 These data highlight and improve the definition of the immunological basis of the disease and suggest a role for dysregulation of the gut microbiota in the pathogenesis of colitis. 24414342 7 74 theme amount 962:967 arg1 quantification 876:889 quantification 876:889 quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae 876:1034 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 8 75 theme component 1216:1224 arg1 analysis 1226:1233 principal component analysis 1206:1233 principal component analysis 1206:1233 Diversity and community structure were analysed by terminal restriction fragment length polymorphism (T-RFLP) patterns, and principal component analysis was utilized on immunological and T-RFLP patterns. 24414342 0 76 theme sulfate 69:75 arg1 sodium 77:82 dextran sulfate sodium 61:82 dextran sulfate sodium (DSS) administration in mice 61:111 Immunological alteration and changes of gut microbiota after dextran sulfate sodium (DSS) administration in mice. 24414342 0 76 theme sulfate 69:75 arg1 DSS 85:87 DSS 85:87 DSS 85:87 Immunological alteration and changes of gut microbiota after dextran sulfate sodium (DSS) administration in mice. 24414342 6 77 theme lymph 809:813 arg1 nodes 815:819 mesenteric lymph nodes 798:819 mesenteric lymph nodes 798:819 Immunological changes were assessed by flow cytometry in spleen, Peyer's patches and mesenteric lymph nodes and through multiplex cytokine profiling. 24414342 2 78 theme sodium 236:241 arg1 Administration 202:215 Administration 202:215 Administration of dextran sulfate sodium (DSS) to animals 202:258 Administration of dextran sulfate sodium (DSS) to animals is a frequently used model to mimic human colitis. 24414342 2 78 theme sodium 236:241 arg1 model 281:285 a frequently used model 263:285 a frequently used model to mimic human colitis 263:308 Administration of dextran sulfate sodium (DSS) to animals is a frequently used model to mimic human colitis. 24414342 8 79 theme polymorphism 1170:1181 arg1 patterns 1192:1199 terminal restriction fragment length polymorphism (T-RFLP) patterns 1133:1199 terminal restriction fragment length polymorphism (T-RFLP) patterns 1133:1199 Diversity and community structure were analysed by terminal restriction fragment length polymorphism (T-RFLP) patterns, and principal component analysis was utilized on immunological and T-RFLP patterns. 24414342 7 80 from mucosa 934:939 arg1 amount 962:967 the total amount 952:967 the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae 894:1034 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 7 80 from mucosa 934:939 arg1 Desulfovibrio 999:1011 Desulfovibrio 999:1011 Desulfovibrio 999:1011 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 7 80 from mucosa 934:939 arg1 amount 904:909 the total amount 894:909 the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae 894:1034 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 7 80 from mucosa 934:939 arg1 Enterobacteriaceae 1017:1034 Enterobacteriaceae 1017:1034 Enterobacteriaceae 1017:1034 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 7 80 from mucosa 934:939 arg1 lactobacilli 972:983 lactobacilli 972:983 lactobacilli 972:983 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 7 80 from mucosa 934:939 arg1 Akkermansia 986:996 Akkermansia 986:996 Akkermansia 986:996 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 7 80 from mucosa 934:939 arg1 bacteria 914:921 bacteria 914:921 bacteria on colonic mucosa 914:939 In addition, quantification of the total amount of bacteria on colonic mucosa as well as the total amount of lactobacilli, Akkermansia, Desulfovibrio and Enterobacteriaceae was performed by the use of quantitative PCR. 24414342 0 81 theme dextran 61:67 arg1 sodium 77:82 dextran sulfate sodium 61:82 dextran sulfate sodium (DSS) administration in mice 61:111 Immunological alteration and changes of gut microbiota after dextran sulfate sodium (DSS) administration in mice. 24414342 0 81 theme dextran 61:67 arg1 DSS 85:87 DSS 85:87 DSS 85:87 Immunological alteration and changes of gut microbiota after dextran sulfate sodium (DSS) administration in mice. 24414342 2 82 theme sulfate 228:234 arg1 sodium 236:241 dextran sulfate sodium 220:241 dextran sulfate sodium (DSS) 220:247 Administration of dextran sulfate sodium (DSS) to animals is a frequently used model to mimic human colitis. 24414342 2 82 theme sulfate 228:234 arg1 DSS 244:246 DSS 244:246 DSS 244:246 Administration of dextran sulfate sodium (DSS) to animals is a frequently used model to mimic human colitis. 24414342 6 83 theme Immunological 713:725 arg1 changes 727:733 Immunological changes 713:733 Immunological changes 713:733 Immunological changes were assessed by flow cytometry in spleen, Peyer's patches and mesenteric lymph nodes and through multiplex cytokine profiling. 24414342 4 84 theme immune 572:577 arg1 system 579:584 the immune system 568:584 the immune system 568:584 To enlarge the understanding of the pathogenesis, we have studied the effect of DSS on the immune system and gut microbiota in mice. 27432787 2 0 theme commercial 543:552 arg1 sorbents 583:590 commercial ZIC-HILIC and other reported sorbents 543:590 commercial ZIC-HILIC and other reported sorbents 543:590 A polyethylenimine functionalized sorbent described here demonstrates good enrichment ability and excellent selectivity towards acidic glycopeptides (e.g. sialylated glycopeptides), even at 1:3000 mass ratio of target glycopeptides and non-glycopeptides, which is much more superior to commercial ZIC-HILIC and other reported sorbents. 27432787 2 1 gly glycopeptides 475:487 arg2 glycopeptides 475:487 target glycopeptides 468:487 target glycopeptides 468:487 A polyethylenimine functionalized sorbent described here demonstrates good enrichment ability and excellent selectivity towards acidic glycopeptides (e.g. sialylated glycopeptides), even at 1:3000 mass ratio of target glycopeptides and non-glycopeptides, which is much more superior to commercial ZIC-HILIC and other reported sorbents. 27432787 2 2 theme sialylated 412:421 arg1 glycopeptides 423:435 sialylated glycopeptides 412:435 sialylated glycopeptides 412:435 A polyethylenimine functionalized sorbent described here demonstrates good enrichment ability and excellent selectivity towards acidic glycopeptides (e.g. sialylated glycopeptides), even at 1:3000 mass ratio of target glycopeptides and non-glycopeptides, which is much more superior to commercial ZIC-HILIC and other reported sorbents. 27432787 2 2 theme sialylated 412:421 arg1 glycopeptides 392:404 acidic glycopeptides 385:404 acidic glycopeptides (e.g. sialylated glycopeptides) 385:436 A polyethylenimine functionalized sorbent described here demonstrates good enrichment ability and excellent selectivity towards acidic glycopeptides (e.g. sialylated glycopeptides), even at 1:3000 mass ratio of target glycopeptides and non-glycopeptides, which is much more superior to commercial ZIC-HILIC and other reported sorbents. 27432787 1 3 gly glycopeptides 242:254 arg2 glycopeptides 242:254 low abundance glycopeptides 228:254 low abundance glycopeptides 228:254 Selective enrichment and purification of N-glycopeptides from complex biological samples is often a necessary step for effective identification of low abundance glycopeptides. 27432787 2 4 dep glycopeptides 423:435 arg1 e.g. 407:410 e.g. 407:410 e.g. 407:410 A polyethylenimine functionalized sorbent described here demonstrates good enrichment ability and excellent selectivity towards acidic glycopeptides (e.g. sialylated glycopeptides), even at 1:3000 mass ratio of target glycopeptides and non-glycopeptides, which is much more superior to commercial ZIC-HILIC and other reported sorbents. 27432787 4 5 theme binding 716:722 arg1 capacity 724:731 its large binding capacity 706:731 its large binding capacity (∼220mg/g for fetuin) 706:753 Another desirable feature of such sorbent is its large binding capacity (∼220mg/g for fetuin). 27432787 3 6 theme effective 607:615 arg1 enrichment 617:626 effective enrichment 607:626 effective enrichment for neutral glycopeptides (IgG) 607:658 It also shows effective enrichment for neutral glycopeptides (IgG). 27432787 2 7 theme enrichment 332:341 arg1 ability 343:349 good enrichment ability 327:349 good enrichment ability 327:349 A polyethylenimine functionalized sorbent described here demonstrates good enrichment ability and excellent selectivity towards acidic glycopeptides (e.g. sialylated glycopeptides), even at 1:3000 mass ratio of target glycopeptides and non-glycopeptides, which is much more superior to commercial ZIC-HILIC and other reported sorbents. 27432787 1 8 from samples 162:168 arg1 purification 106:117 purification 106:117 purification 106:117 Selective enrichment and purification of N-glycopeptides from complex biological samples is often a necessary step for effective identification of low abundance glycopeptides. 27432787 1 8 from samples 162:168 arg1 step 191:194 a necessary step 179:194 a necessary step for effective identification of low abundance glycopeptides 179:254 Selective enrichment and purification of N-glycopeptides from complex biological samples is often a necessary step for effective identification of low abundance glycopeptides. 27432787 1 8 from samples 162:168 arg1 enrichment 91:100 Selective enrichment 81:100 Selective enrichment 81:100 Selective enrichment and purification of N-glycopeptides from complex biological samples is often a necessary step for effective identification of low abundance glycopeptides. 27432787 0 9 gly glycopeptides 66:78 arg2 glycopeptides 66:78 N-linked glycopeptides 57:78 N-linked glycopeptides 57:78 A highly selective hydrophilic sorbent for enrichment of N-linked glycopeptides. 27432787 2 10 theme acidic 385:390 arg1 glycopeptides 423:435 sialylated glycopeptides 412:435 sialylated glycopeptides 412:435 A polyethylenimine functionalized sorbent described here demonstrates good enrichment ability and excellent selectivity towards acidic glycopeptides (e.g. sialylated glycopeptides), even at 1:3000 mass ratio of target glycopeptides and non-glycopeptides, which is much more superior to commercial ZIC-HILIC and other reported sorbents. 27432787 2 10 theme acidic 385:390 arg1 glycopeptides 392:404 acidic glycopeptides 385:404 acidic glycopeptides (e.g. sialylated glycopeptides) 385:436 A polyethylenimine functionalized sorbent described here demonstrates good enrichment ability and excellent selectivity towards acidic glycopeptides (e.g. sialylated glycopeptides), even at 1:3000 mass ratio of target glycopeptides and non-glycopeptides, which is much more superior to commercial ZIC-HILIC and other reported sorbents. 27432787 2 11 theme reported 574:581 arg1 sorbents 583:590 commercial ZIC-HILIC and other reported sorbents 543:590 commercial ZIC-HILIC and other reported sorbents 543:590 A polyethylenimine functionalized sorbent described here demonstrates good enrichment ability and excellent selectivity towards acidic glycopeptides (e.g. sialylated glycopeptides), even at 1:3000 mass ratio of target glycopeptides and non-glycopeptides, which is much more superior to commercial ZIC-HILIC and other reported sorbents. 27432787 3 12 gly glycopeptides 640:652 arg2 glycopeptides 640:652 neutral glycopeptides 632:652 neutral glycopeptides (IgG) 632:658 It also shows effective enrichment for neutral glycopeptides (IgG). 27432787 3 12 gly glycopeptides 640:652 arg2 IgG 655:657 IgG 655:657 IgG 655:657 It also shows effective enrichment for neutral glycopeptides (IgG). 27432787 4 13 theme such 690:693 arg1 sorbent 695:701 such sorbent 690:701 such sorbent 690:701 Another desirable feature of such sorbent is its large binding capacity (∼220mg/g for fetuin). 27432787 2 14 theme good 327:330 arg1 ability 343:349 good enrichment ability 327:349 good enrichment ability 327:349 A polyethylenimine functionalized sorbent described here demonstrates good enrichment ability and excellent selectivity towards acidic glycopeptides (e.g. sialylated glycopeptides), even at 1:3000 mass ratio of target glycopeptides and non-glycopeptides, which is much more superior to commercial ZIC-HILIC and other reported sorbents. 27432787 1 15 theme necessary 181:189 arg1 purification 106:117 purification 106:117 purification 106:117 Selective enrichment and purification of N-glycopeptides from complex biological samples is often a necessary step for effective identification of low abundance glycopeptides. 27432787 1 15 theme necessary 181:189 arg1 step 191:194 a necessary step 179:194 a necessary step for effective identification of low abundance glycopeptides 179:254 Selective enrichment and purification of N-glycopeptides from complex biological samples is often a necessary step for effective identification of low abundance glycopeptides. 27432787 1 15 theme necessary 181:189 arg1 enrichment 91:100 Selective enrichment 81:100 Selective enrichment 81:100 Selective enrichment and purification of N-glycopeptides from complex biological samples is often a necessary step for effective identification of low abundance glycopeptides. 27432787 2 16 theme other 568:572 arg1 sorbents 583:590 commercial ZIC-HILIC and other reported sorbents 543:590 commercial ZIC-HILIC and other reported sorbents 543:590 A polyethylenimine functionalized sorbent described here demonstrates good enrichment ability and excellent selectivity towards acidic glycopeptides (e.g. sialylated glycopeptides), even at 1:3000 mass ratio of target glycopeptides and non-glycopeptides, which is much more superior to commercial ZIC-HILIC and other reported sorbents. 27432787 1 17 theme Selective 81:89 arg1 purification 106:117 purification 106:117 purification 106:117 Selective enrichment and purification of N-glycopeptides from complex biological samples is often a necessary step for effective identification of low abundance glycopeptides. 27432787 1 17 theme Selective 81:89 arg1 step 191:194 a necessary step 179:194 a necessary step for effective identification of low abundance glycopeptides 179:254 Selective enrichment and purification of N-glycopeptides from complex biological samples is often a necessary step for effective identification of low abundance glycopeptides. 27432787 1 17 theme Selective 81:89 arg1 enrichment 91:100 Selective enrichment 81:100 Selective enrichment 81:100 Selective enrichment and purification of N-glycopeptides from complex biological samples is often a necessary step for effective identification of low abundance glycopeptides. 27432787 2 18 theme 1:3000 447:452 arg1 mass 454:457 mass 454:457 mass 454:457 A polyethylenimine functionalized sorbent described here demonstrates good enrichment ability and excellent selectivity towards acidic glycopeptides (e.g. sialylated glycopeptides), even at 1:3000 mass ratio of target glycopeptides and non-glycopeptides, which is much more superior to commercial ZIC-HILIC and other reported sorbents. 27432787 3 19 theme neutral 632:638 arg1 IgG 655:657 IgG 655:657 IgG 655:657 It also shows effective enrichment for neutral glycopeptides (IgG). 27432787 3 19 theme neutral 632:638 arg1 glycopeptides 640:652 neutral glycopeptides 632:652 neutral glycopeptides (IgG) 632:658 It also shows effective enrichment for neutral glycopeptides (IgG). 27432787 1 20 theme effective 200:208 arg1 identification 210:223 effective identification 200:223 effective identification of low abundance glycopeptides 200:254 Selective enrichment and purification of N-glycopeptides from complex biological samples is often a necessary step for effective identification of low abundance glycopeptides. 27432787 0 21 theme hydrophilic 19:29 arg1 sorbent 31:37 A highly selective hydrophilic sorbent 0:37 A highly selective hydrophilic sorbent for enrichment of N-linked glycopeptides 0:78 A highly selective hydrophilic sorbent for enrichment of N-linked glycopeptides. 27432787 2 22 theme excellent 355:363 arg1 selectivity 365:375 excellent selectivity 355:375 excellent selectivity towards acidic glycopeptides (e.g. sialylated glycopeptides) 355:436 A polyethylenimine functionalized sorbent described here demonstrates good enrichment ability and excellent selectivity towards acidic glycopeptides (e.g. sialylated glycopeptides), even at 1:3000 mass ratio of target glycopeptides and non-glycopeptides, which is much more superior to commercial ZIC-HILIC and other reported sorbents. 27432787 2 23 theme glycopeptides 475:487 arg1 ratio 459:463 1:3000 mass ratio 447:463 1:3000 mass ratio 447:463 A polyethylenimine functionalized sorbent described here demonstrates good enrichment ability and excellent selectivity towards acidic glycopeptides (e.g. sialylated glycopeptides), even at 1:3000 mass ratio of target glycopeptides and non-glycopeptides, which is much more superior to commercial ZIC-HILIC and other reported sorbents. 27432787 0 24 theme selective 9:17 arg1 sorbent 31:37 A highly selective hydrophilic sorbent 0:37 A highly selective hydrophilic sorbent for enrichment of N-linked glycopeptides 0:78 A highly selective hydrophilic sorbent for enrichment of N-linked glycopeptides. 27432787 1 25 gly N-glycopeptides 122:136 arg2 N-glycopeptides 122:136 N-glycopeptides 122:136 N-glycopeptides 122:136 Selective enrichment and purification of N-glycopeptides from complex biological samples is often a necessary step for effective identification of low abundance glycopeptides. 27432787 2 26 theme target 468:473 arg1 glycopeptides 475:487 target glycopeptides 468:487 target glycopeptides 468:487 A polyethylenimine functionalized sorbent described here demonstrates good enrichment ability and excellent selectivity towards acidic glycopeptides (e.g. sialylated glycopeptides), even at 1:3000 mass ratio of target glycopeptides and non-glycopeptides, which is much more superior to commercial ZIC-HILIC and other reported sorbents. 27432787 2 27 gly sialylated 412:421 arg1 glycopeptides 423:435 sialylated glycopeptides 412:435 sialylated glycopeptides 412:435 A polyethylenimine functionalized sorbent described here demonstrates good enrichment ability and excellent selectivity towards acidic glycopeptides (e.g. sialylated glycopeptides), even at 1:3000 mass ratio of target glycopeptides and non-glycopeptides, which is much more superior to commercial ZIC-HILIC and other reported sorbents. 27432787 2 27 gly sialylated 412:421 arg1 glycopeptides 392:404 acidic glycopeptides 385:404 acidic glycopeptides (e.g. sialylated glycopeptides) 385:436 A polyethylenimine functionalized sorbent described here demonstrates good enrichment ability and excellent selectivity towards acidic glycopeptides (e.g. sialylated glycopeptides), even at 1:3000 mass ratio of target glycopeptides and non-glycopeptides, which is much more superior to commercial ZIC-HILIC and other reported sorbents. 27432787 2 28 theme polyethylenimine 259:274 arg1 sorbent 291:297 A polyethylenimine functionalized sorbent 257:297 A polyethylenimine functionalized sorbent described here 257:312 A polyethylenimine functionalized sorbent described here demonstrates good enrichment ability and excellent selectivity towards acidic glycopeptides (e.g. sialylated glycopeptides), even at 1:3000 mass ratio of target glycopeptides and non-glycopeptides, which is much more superior to commercial ZIC-HILIC and other reported sorbents. 27432787 1 29 theme low 228:230 arg1 glycopeptides 242:254 low abundance glycopeptides 228:254 low abundance glycopeptides 228:254 Selective enrichment and purification of N-glycopeptides from complex biological samples is often a necessary step for effective identification of low abundance glycopeptides. 27432787 2 30 theme mass 454:457 arg1 ratio 459:463 1:3000 mass ratio 447:463 1:3000 mass ratio 447:463 A polyethylenimine functionalized sorbent described here demonstrates good enrichment ability and excellent selectivity towards acidic glycopeptides (e.g. sialylated glycopeptides), even at 1:3000 mass ratio of target glycopeptides and non-glycopeptides, which is much more superior to commercial ZIC-HILIC and other reported sorbents. 27432787 2 31 gly glycopeptides 423:435 arg2 glycopeptides 423:435 sialylated glycopeptides 412:435 sialylated glycopeptides 412:435 A polyethylenimine functionalized sorbent described here demonstrates good enrichment ability and excellent selectivity towards acidic glycopeptides (e.g. sialylated glycopeptides), even at 1:3000 mass ratio of target glycopeptides and non-glycopeptides, which is much more superior to commercial ZIC-HILIC and other reported sorbents. 27432787 2 31 gly glycopeptides 423:435 arg2 glycopeptides 392:404 acidic glycopeptides 385:404 acidic glycopeptides (e.g. sialylated glycopeptides) 385:436 A polyethylenimine functionalized sorbent described here demonstrates good enrichment ability and excellent selectivity towards acidic glycopeptides (e.g. sialylated glycopeptides), even at 1:3000 mass ratio of target glycopeptides and non-glycopeptides, which is much more superior to commercial ZIC-HILIC and other reported sorbents. 27432787 2 32 theme non-glycopeptides 493:509 arg1 ratio 459:463 1:3000 mass ratio 447:463 1:3000 mass ratio 447:463 A polyethylenimine functionalized sorbent described here demonstrates good enrichment ability and excellent selectivity towards acidic glycopeptides (e.g. sialylated glycopeptides), even at 1:3000 mass ratio of target glycopeptides and non-glycopeptides, which is much more superior to commercial ZIC-HILIC and other reported sorbents. 27432787 1 33 theme abundance 232:240 arg1 glycopeptides 242:254 low abundance glycopeptides 228:254 low abundance glycopeptides 228:254 Selective enrichment and purification of N-glycopeptides from complex biological samples is often a necessary step for effective identification of low abundance glycopeptides. 27432787 2 34 theme ZIC-HILIC 554:562 arg1 sorbents 583:590 commercial ZIC-HILIC and other reported sorbents 543:590 commercial ZIC-HILIC and other reported sorbents 543:590 A polyethylenimine functionalized sorbent described here demonstrates good enrichment ability and excellent selectivity towards acidic glycopeptides (e.g. sialylated glycopeptides), even at 1:3000 mass ratio of target glycopeptides and non-glycopeptides, which is much more superior to commercial ZIC-HILIC and other reported sorbents. 27432787 1 35 theme N-glycopeptides 122:136 arg1 purification 106:117 purification 106:117 purification 106:117 Selective enrichment and purification of N-glycopeptides from complex biological samples is often a necessary step for effective identification of low abundance glycopeptides. 27432787 1 35 theme N-glycopeptides 122:136 arg1 step 191:194 a necessary step 179:194 a necessary step for effective identification of low abundance glycopeptides 179:254 Selective enrichment and purification of N-glycopeptides from complex biological samples is often a necessary step for effective identification of low abundance glycopeptides. 27432787 1 35 theme N-glycopeptides 122:136 arg1 enrichment 91:100 Selective enrichment 81:100 Selective enrichment 81:100 Selective enrichment and purification of N-glycopeptides from complex biological samples is often a necessary step for effective identification of low abundance glycopeptides. 27432787 2 36 theme functionalized 276:289 arg1 sorbent 291:297 A polyethylenimine functionalized sorbent 257:297 A polyethylenimine functionalized sorbent described here 257:312 A polyethylenimine functionalized sorbent described here demonstrates good enrichment ability and excellent selectivity towards acidic glycopeptides (e.g. sialylated glycopeptides), even at 1:3000 mass ratio of target glycopeptides and non-glycopeptides, which is much more superior to commercial ZIC-HILIC and other reported sorbents. 27432787 0 37 link N-linked 57:64 arg1 glycopeptides 66:78 N-linked glycopeptides 57:78 N-linked glycopeptides 57:78 A highly selective hydrophilic sorbent for enrichment of N-linked glycopeptides. 27432787 1 38 theme complex 143:149 arg1 samples 162:168 complex biological samples 143:168 complex biological samples 143:168 Selective enrichment and purification of N-glycopeptides from complex biological samples is often a necessary step for effective identification of low abundance glycopeptides. 27432787 1 39 theme glycopeptides 242:254 arg1 identification 210:223 effective identification 200:223 effective identification of low abundance glycopeptides 200:254 Selective enrichment and purification of N-glycopeptides from complex biological samples is often a necessary step for effective identification of low abundance glycopeptides. 27432787 2 40 gly glycopeptides 392:404 arg2 glycopeptides 423:435 sialylated glycopeptides 412:435 sialylated glycopeptides 412:435 A polyethylenimine functionalized sorbent described here demonstrates good enrichment ability and excellent selectivity towards acidic glycopeptides (e.g. sialylated glycopeptides), even at 1:3000 mass ratio of target glycopeptides and non-glycopeptides, which is much more superior to commercial ZIC-HILIC and other reported sorbents. 27432787 2 40 gly glycopeptides 392:404 arg2 glycopeptides 392:404 acidic glycopeptides 385:404 acidic glycopeptides (e.g. sialylated glycopeptides) 385:436 A polyethylenimine functionalized sorbent described here demonstrates good enrichment ability and excellent selectivity towards acidic glycopeptides (e.g. sialylated glycopeptides), even at 1:3000 mass ratio of target glycopeptides and non-glycopeptides, which is much more superior to commercial ZIC-HILIC and other reported sorbents. 27432787 4 41 dep capacity 724:731 arg1 ∼220mg/g 734:741 ∼220mg/g 734:741 ∼220mg/g for fetuin 734:752 Another desirable feature of such sorbent is its large binding capacity (∼220mg/g for fetuin). 27432787 1 42 theme biological 151:160 arg1 samples 162:168 complex biological samples 143:168 complex biological samples 143:168 Selective enrichment and purification of N-glycopeptides from complex biological samples is often a necessary step for effective identification of low abundance glycopeptides. 27432787 0 43 theme glycopeptides 66:78 arg1 enrichment 43:52 enrichment 43:52 enrichment of N-linked glycopeptides 43:78 A highly selective hydrophilic sorbent for enrichment of N-linked glycopeptides. 27432787 4 44 theme sorbent 695:701 arg1 feature 679:685 Another desirable feature 661:685 Another desirable feature of such sorbent 661:701 Another desirable feature of such sorbent is its large binding capacity (∼220mg/g for fetuin). 27432787 4 45 theme large 710:714 arg1 capacity 724:731 its large binding capacity 706:731 its large binding capacity (∼220mg/g for fetuin) 706:753 Another desirable feature of such sorbent is its large binding capacity (∼220mg/g for fetuin). 27432787 0 46 theme N-linked 57:64 arg1 glycopeptides 66:78 N-linked glycopeptides 57:78 N-linked glycopeptides 57:78 A highly selective hydrophilic sorbent for enrichment of N-linked glycopeptides. 27432787 2 47 gly non-glycopeptides 493:509 arg2 non-glycopeptides 493:509 non-glycopeptides 493:509 non-glycopeptides 493:509 A polyethylenimine functionalized sorbent described here demonstrates good enrichment ability and excellent selectivity towards acidic glycopeptides (e.g. sialylated glycopeptides), even at 1:3000 mass ratio of target glycopeptides and non-glycopeptides, which is much more superior to commercial ZIC-HILIC and other reported sorbents. 27432787 4 48 theme desirable 669:677 arg1 feature 679:685 Another desirable feature 661:685 Another desirable feature of such sorbent 661:701 Another desirable feature of such sorbent is its large binding capacity (∼220mg/g for fetuin). 25318123 0 0 theme virus 86:90 arg1 infections 92:101 acute virus infections 80:101 acute virus infections 80:101 Viral resistance of MOGS-CDG patients implies a broad-spectrum strategy against acute virus infections. 25318123 1 1 theme reticulum 320:328 arg1 glucosidase 335:345 endoplasmic reticulum (ER) glucosidase I 308:347 endoplasmic reticulum (ER) glucosidase I 308:347 Sadat et al. reported in the 24 April 2014 issue of the New England Journal of Medicine that patients genetically deficient in the gene encoding mannosyl-oligosaccharide glucosidase (MOGS), also known as endoplasmic reticulum (ER) glucosidase I, manifested a severe hypogammaglobulinaemia without clinical evidence of an infectious diathesis. 25318123 0 2 theme acute 80:84 arg1 infections 92:101 acute virus infections 80:101 acute virus infections 80:101 Viral resistance of MOGS-CDG patients implies a broad-spectrum strategy against acute virus infections. 25318123 3 3 theme ER 684:685 arg1 glucosidases 687:698 ER glucosidases 684:698 ER glucosidases 684:698 This finding unambiguously validates ER glucosidases as valuable targets for antiviral agents against a broad-spectrum of enveloped viruses. 25318123 3 3 theme ER 684:685 arg1 targets 712:718 valuable targets 703:718 valuable targets for antiviral agents against a broad-spectrum of enveloped viruses 703:785 This finding unambiguously validates ER glucosidases as valuable targets for antiviral agents against a broad-spectrum of enveloped viruses. 25318123 1 4 theme ER 331:332 arg1 glucosidase 335:345 endoplasmic reticulum (ER) glucosidase I 308:347 endoplasmic reticulum (ER) glucosidase I 308:347 Sadat et al. reported in the 24 April 2014 issue of the New England Journal of Medicine that patients genetically deficient in the gene encoding mannosyl-oligosaccharide glucosidase (MOGS), also known as endoplasmic reticulum (ER) glucosidase I, manifested a severe hypogammaglobulinaemia without clinical evidence of an infectious diathesis. 25318123 1 5 theme infectious 425:434 arg1 diathesis 436:444 an infectious diathesis 422:444 an infectious diathesis 422:444 Sadat et al. reported in the 24 April 2014 issue of the New England Journal of Medicine that patients genetically deficient in the gene encoding mannosyl-oligosaccharide glucosidase (MOGS), also known as endoplasmic reticulum (ER) glucosidase I, manifested a severe hypogammaglobulinaemia without clinical evidence of an infectious diathesis. 25318123 3 6 theme antiviral 724:732 arg1 agents 734:739 antiviral agents 724:739 antiviral agents against a broad-spectrum of enveloped viruses 724:785 This finding unambiguously validates ER glucosidases as valuable targets for antiviral agents against a broad-spectrum of enveloped viruses. 25318123 1 7 theme diathesis 436:444 arg1 evidence 410:417 clinical evidence 401:417 clinical evidence of an infectious diathesis 401:444 Sadat et al. reported in the 24 April 2014 issue of the New England Journal of Medicine that patients genetically deficient in the gene encoding mannosyl-oligosaccharide glucosidase (MOGS), also known as endoplasmic reticulum (ER) glucosidase I, manifested a severe hypogammaglobulinaemia without clinical evidence of an infectious diathesis. 25318123 2 8 link N-linked 514:521 arg1 processing 530:539 the impaired N-linked glycan processing 501:539 the impaired N-linked glycan processing of the patients 501:555 This paradox phenomenon is, at least in part, because the impaired N-linked glycan processing of the patients compromises their ability to support efficient replication and cellular entry of viruses. 25318123 1 9 theme mannosyl-oligosaccharide 249:272 arg1 MOGS 287:290 MOGS 287:290 MOGS 287:290 Sadat et al. reported in the 24 April 2014 issue of the New England Journal of Medicine that patients genetically deficient in the gene encoding mannosyl-oligosaccharide glucosidase (MOGS), also known as endoplasmic reticulum (ER) glucosidase I, manifested a severe hypogammaglobulinaemia without clinical evidence of an infectious diathesis. 25318123 1 9 theme mannosyl-oligosaccharide 249:272 arg1 glucosidase 274:284 mannosyl-oligosaccharide glucosidase 249:284 mannosyl-oligosaccharide glucosidase (MOGS) 249:291 Sadat et al. reported in the 24 April 2014 issue of the New England Journal of Medicine that patients genetically deficient in the gene encoding mannosyl-oligosaccharide glucosidase (MOGS), also known as endoplasmic reticulum (ER) glucosidase I, manifested a severe hypogammaglobulinaemia without clinical evidence of an infectious diathesis. 25318123 2 10 theme cellular 620:627 arg1 entry 629:633 cellular entry 620:633 cellular entry 620:633 This paradox phenomenon is, at least in part, because the impaired N-linked glycan processing of the patients compromises their ability to support efficient replication and cellular entry of viruses. 25318123 0 11 theme Viral 0:4 arg1 resistance 6:15 Viral resistance 0:15 Viral resistance of MOGS-CDG patients 0:36 Viral resistance of MOGS-CDG patients implies a broad-spectrum strategy against acute virus infections. 25318123 2 12 theme efficient 594:602 arg1 replication 604:614 efficient replication 594:614 efficient replication 594:614 This paradox phenomenon is, at least in part, because the impaired N-linked glycan processing of the patients compromises their ability to support efficient replication and cellular entry of viruses. 25318123 0 13 theme MOGS-CDG 20:27 arg1 patients 29:36 MOGS-CDG patients 20:36 MOGS-CDG patients 20:36 Viral resistance of MOGS-CDG patients implies a broad-spectrum strategy against acute virus infections. 25318123 1 14 theme Journal 172:178 arg1 issue 147:151 the 24 April 2014 issue 129:151 the 24 April 2014 issue of the New England Journal of Medicine 129:190 Sadat et al. reported in the 24 April 2014 issue of the New England Journal of Medicine that patients genetically deficient in the gene encoding mannosyl-oligosaccharide glucosidase (MOGS), also known as endoplasmic reticulum (ER) glucosidase I, manifested a severe hypogammaglobulinaemia without clinical evidence of an infectious diathesis. 25318123 2 15 theme glycan 523:528 arg1 processing 530:539 the impaired N-linked glycan processing 501:539 the impaired N-linked glycan processing of the patients 501:555 This paradox phenomenon is, at least in part, because the impaired N-linked glycan processing of the patients compromises their ability to support efficient replication and cellular entry of viruses. 25318123 2 16 theme N-linked 514:521 arg1 processing 530:539 the impaired N-linked glycan processing 501:539 the impaired N-linked glycan processing of the patients 501:555 This paradox phenomenon is, at least in part, because the impaired N-linked glycan processing of the patients compromises their ability to support efficient replication and cellular entry of viruses. 25318123 1 17 theme Medicine 183:190 arg1 issue 147:151 the 24 April 2014 issue 129:151 the 24 April 2014 issue of the New England Journal of Medicine 129:190 Sadat et al. reported in the 24 April 2014 issue of the New England Journal of Medicine that patients genetically deficient in the gene encoding mannosyl-oligosaccharide glucosidase (MOGS), also known as endoplasmic reticulum (ER) glucosidase I, manifested a severe hypogammaglobulinaemia without clinical evidence of an infectious diathesis. 25318123 0 18 theme patients 29:36 arg1 resistance 6:15 Viral resistance 0:15 Viral resistance of MOGS-CDG patients 0:36 Viral resistance of MOGS-CDG patients implies a broad-spectrum strategy against acute virus infections. 25318123 1 19 from gene 235:238 arg1 deficient 218:226 deficient 218:226 deficient 218:226 Sadat et al. reported in the 24 April 2014 issue of the New England Journal of Medicine that patients genetically deficient in the gene encoding mannosyl-oligosaccharide glucosidase (MOGS), also known as endoplasmic reticulum (ER) glucosidase I, manifested a severe hypogammaglobulinaemia without clinical evidence of an infectious diathesis. 25318123 1 20 theme severe 363:368 arg1 hypogammaglobulinaemia 370:391 a severe hypogammaglobulinaemia 361:391 a severe hypogammaglobulinaemia without clinical evidence of an infectious diathesis 361:444 Sadat et al. reported in the 24 April 2014 issue of the New England Journal of Medicine that patients genetically deficient in the gene encoding mannosyl-oligosaccharide glucosidase (MOGS), also known as endoplasmic reticulum (ER) glucosidase I, manifested a severe hypogammaglobulinaemia without clinical evidence of an infectious diathesis. 25318123 0 21 theme broad-spectrum 48:61 arg1 strategy 63:70 a broad-spectrum strategy 46:70 a broad-spectrum strategy against acute virus infections 46:101 Viral resistance of MOGS-CDG patients implies a broad-spectrum strategy against acute virus infections. 25318123 1 22 from deficient 218:226 arg1 gene 235:238 the gene 231:238 the gene encoding mannosyl-oligosaccharide glucosidase (MOGS), also known as endoplasmic reticulum (ER) glucosidase I, 231:348 Sadat et al. reported in the 24 April 2014 issue of the New England Journal of Medicine that patients genetically deficient in the gene encoding mannosyl-oligosaccharide glucosidase (MOGS), also known as endoplasmic reticulum (ER) glucosidase I, manifested a severe hypogammaglobulinaemia without clinical evidence of an infectious diathesis. 25318123 2 23 theme impaired 505:512 arg1 processing 530:539 the impaired N-linked glycan processing 501:539 the impaired N-linked glycan processing of the patients 501:555 This paradox phenomenon is, at least in part, because the impaired N-linked glycan processing of the patients compromises their ability to support efficient replication and cellular entry of viruses. 25318123 3 24 theme enveloped 769:777 arg1 viruses 779:785 enveloped viruses 769:785 enveloped viruses 769:785 This finding unambiguously validates ER glucosidases as valuable targets for antiviral agents against a broad-spectrum of enveloped viruses. 25318123 2 25 theme patients 548:555 arg1 processing 530:539 the impaired N-linked glycan processing 501:539 the impaired N-linked glycan processing of the patients 501:555 This paradox phenomenon is, at least in part, because the impaired N-linked glycan processing of the patients compromises their ability to support efficient replication and cellular entry of viruses. 25318123 3 26 theme viruses 779:785 arg1 broad-spectrum 751:764 a broad-spectrum 749:764 a broad-spectrum of enveloped viruses 749:785 This finding unambiguously validates ER glucosidases as valuable targets for antiviral agents against a broad-spectrum of enveloped viruses. 25318123 1 27 theme clinical 401:408 arg1 evidence 410:417 clinical evidence 401:417 clinical evidence of an infectious diathesis 401:444 Sadat et al. reported in the 24 April 2014 issue of the New England Journal of Medicine that patients genetically deficient in the gene encoding mannosyl-oligosaccharide glucosidase (MOGS), also known as endoplasmic reticulum (ER) glucosidase I, manifested a severe hypogammaglobulinaemia without clinical evidence of an infectious diathesis. 25318123 2 28 theme viruses 638:644 arg1 replication 604:614 efficient replication 594:614 efficient replication 594:614 This paradox phenomenon is, at least in part, because the impaired N-linked glycan processing of the patients compromises their ability to support efficient replication and cellular entry of viruses. 25318123 2 28 theme viruses 638:644 arg1 entry 629:633 cellular entry 620:633 cellular entry 620:633 This paradox phenomenon is, at least in part, because the impaired N-linked glycan processing of the patients compromises their ability to support efficient replication and cellular entry of viruses. 25318123 1 29 theme deficient 218:226 arg1 patients 197:204 patients 197:204 patients genetically deficient in the gene encoding mannosyl-oligosaccharide glucosidase (MOGS), also known as endoplasmic reticulum (ER) glucosidase I, 197:348 Sadat et al. reported in the 24 April 2014 issue of the New England Journal of Medicine that patients genetically deficient in the gene encoding mannosyl-oligosaccharide glucosidase (MOGS), also known as endoplasmic reticulum (ER) glucosidase I, manifested a severe hypogammaglobulinaemia without clinical evidence of an infectious diathesis. 25318123 2 30 theme paradox 452:458 arg1 phenomenon 460:469 This paradox phenomenon 447:469 This paradox phenomenon 447:469 This paradox phenomenon is, at least in part, because the impaired N-linked glycan processing of the patients compromises their ability to support efficient replication and cellular entry of viruses. 25318123 1 31 theme endoplasmic 308:318 arg1 glucosidase 335:345 endoplasmic reticulum (ER) glucosidase I 308:347 endoplasmic reticulum (ER) glucosidase I 308:347 Sadat et al. reported in the 24 April 2014 issue of the New England Journal of Medicine that patients genetically deficient in the gene encoding mannosyl-oligosaccharide glucosidase (MOGS), also known as endoplasmic reticulum (ER) glucosidase I, manifested a severe hypogammaglobulinaemia without clinical evidence of an infectious diathesis. 25318123 3 32 theme valuable 703:710 arg1 glucosidases 687:698 ER glucosidases 684:698 ER glucosidases 684:698 This finding unambiguously validates ER glucosidases as valuable targets for antiviral agents against a broad-spectrum of enveloped viruses. 25318123 3 32 theme valuable 703:710 arg1 targets 712:718 valuable targets 703:718 valuable targets for antiviral agents against a broad-spectrum of enveloped viruses 703:785 This finding unambiguously validates ER glucosidases as valuable targets for antiviral agents against a broad-spectrum of enveloped viruses. 25318123 1 33 theme April 136:140 arg1 issue 147:151 the 24 April 2014 issue 129:151 the 24 April 2014 issue of the New England Journal of Medicine 129:190 Sadat et al. reported in the 24 April 2014 issue of the New England Journal of Medicine that patients genetically deficient in the gene encoding mannosyl-oligosaccharide glucosidase (MOGS), also known as endoplasmic reticulum (ER) glucosidase I, manifested a severe hypogammaglobulinaemia without clinical evidence of an infectious diathesis. 24362939 2 0 theme GH85 388:391 arg1 ENGases 393:399 family GH85 ENGases 381:399 family GH85 ENGases 381:399 The synthetic efficiency of a selection of family GH85 ENGases was investigated as the structure of the acceptor substrate was varied. 24362939 1 1 theme defined 270:276 arg1 glycoconjugates 298:312 defined homogenous N-linked glycoconjugates 270:312 defined homogenous N-linked glycoconjugates 270:312 Endo-β-N-Acetylglucosaminidases (ENGases) are highly useful biocatalysts that can be used to synthetically access a wide variety of defined homogenous N-linked glycoconjugates in a convergent manner. 24362939 3 2 with conjunction 549:559 arg1 donors 602:607 penta- and decasaccharide oxazoline donors 566:607 penta- and decasaccharide oxazoline donors 566:607 Several different GlcNAc-asparagine acceptors were synthesised, and used in conjunction with penta- and decasaccharide oxazoline donors. 24362939 1 3 link N-linked 289:296 arg1 glycoconjugates 298:312 defined homogenous N-linked glycoconjugates 270:312 defined homogenous N-linked glycoconjugates 270:312 Endo-β-N-Acetylglucosaminidases (ENGases) are highly useful biocatalysts that can be used to synthetically access a wide variety of defined homogenous N-linked glycoconjugates in a convergent manner. 24362939 1 4 theme useful 191:196 arg1 biocatalysts 198:209 highly useful biocatalysts 184:209 highly useful biocatalysts that can be used to synthetically access a wide variety of defined homogenous N-linked glycoconjugates in a convergent manner 184:335 Endo-β-N-Acetylglucosaminidases (ENGases) are highly useful biocatalysts that can be used to synthetically access a wide variety of defined homogenous N-linked glycoconjugates in a convergent manner. 24362939 1 4 theme useful 191:196 arg1 Endo-β-N-Acetylglucosaminidases 138:168 Endo-β-N-Acetylglucosaminidases 138:168 Endo-β-N-Acetylglucosaminidases (ENGases) 138:178 Endo-β-N-Acetylglucosaminidases (ENGases) are highly useful biocatalysts that can be used to synthetically access a wide variety of defined homogenous N-linked glycoconjugates in a convergent manner. 24362939 1 5 theme homogenous 278:287 arg1 glycoconjugates 298:312 defined homogenous N-linked glycoconjugates 270:312 defined homogenous N-linked glycoconjugates 270:312 Endo-β-N-Acetylglucosaminidases (ENGases) are highly useful biocatalysts that can be used to synthetically access a wide variety of defined homogenous N-linked glycoconjugates in a convergent manner. 24362939 0 6 theme amino 117:121 arg1 acceptor 128:135 the glycosyl amino acid acceptor 104:135 the glycosyl amino acid acceptor 104:135 Endo-β-N-acetylglucosaminidase catalysed glycosylation: tolerance of enzymes to structural variation of the glycosyl amino acid acceptor. 24362939 3 7 theme oxazoline 592:600 arg1 donors 602:607 penta- and decasaccharide oxazoline donors 566:607 penta- and decasaccharide oxazoline donors 566:607 Several different GlcNAc-asparagine acceptors were synthesised, and used in conjunction with penta- and decasaccharide oxazoline donors. 24362939 1 8 theme N-linked 289:296 arg1 glycoconjugates 298:312 defined homogenous N-linked glycoconjugates 270:312 defined homogenous N-linked glycoconjugates 270:312 Endo-β-N-Acetylglucosaminidases (ENGases) are highly useful biocatalysts that can be used to synthetically access a wide variety of defined homogenous N-linked glycoconjugates in a convergent manner. 24362939 0 9 theme glycosyl 108:115 arg1 acceptor 128:135 the glycosyl amino acid acceptor 104:135 the glycosyl amino acid acceptor 104:135 Endo-β-N-acetylglucosaminidase catalysed glycosylation: tolerance of enzymes to structural variation of the glycosyl amino acid acceptor. 24362939 1 10 theme glycoconjugates 298:312 arg1 variety 259:265 a wide variety 252:265 a wide variety of defined homogenous N-linked glycoconjugates 252:312 Endo-β-N-Acetylglucosaminidases (ENGases) are highly useful biocatalysts that can be used to synthetically access a wide variety of defined homogenous N-linked glycoconjugates in a convergent manner. 24362939 1 10 theme glycoconjugates 298:312 arg1 glycoconjugates 298:312 defined homogenous N-linked glycoconjugates 270:312 defined homogenous N-linked glycoconjugates 270:312 Endo-β-N-Acetylglucosaminidases (ENGases) are highly useful biocatalysts that can be used to synthetically access a wide variety of defined homogenous N-linked glycoconjugates in a convergent manner. 24362939 0 11 theme acceptor 128:135 arg1 variation 91:99 structural variation 80:99 structural variation of the glycosyl amino acid acceptor 80:135 Endo-β-N-acetylglucosaminidase catalysed glycosylation: tolerance of enzymes to structural variation of the glycosyl amino acid acceptor. 24362939 6 12 theme protected 924:932 arg1 acceptor 934:941 a 3-O-benzyl protected acceptor 911:941 the use a 3-O-benzyl protected acceptor 903:941 For Endo D the achievable synthetic efficiency was increased by a factor of three by the use a 3-O-benzyl protected acceptor. 24362939 6 13 theme synthetic 844:852 arg1 efficiency 854:863 the achievable synthetic efficiency 829:863 the achievable synthetic efficiency 829:863 For Endo D the achievable synthetic efficiency was increased by a factor of three by the use a 3-O-benzyl protected acceptor. 24362939 0 14 theme acid 123:126 arg1 acceptor 128:135 the glycosyl amino acid acceptor 104:135 the glycosyl amino acid acceptor 104:135 Endo-β-N-acetylglucosaminidase catalysed glycosylation: tolerance of enzymes to structural variation of the glycosyl amino acid acceptor. 24362939 6 15 theme 3-O-benzyl 913:922 arg1 acceptor 934:941 a 3-O-benzyl protected acceptor 911:941 the use a 3-O-benzyl protected acceptor 903:941 For Endo D the achievable synthetic efficiency was increased by a factor of three by the use a 3-O-benzyl protected acceptor. 24362939 7 16 attach presence 948:955 arg1 position-3 972:981 position-3 972:981 position-3 972:981 The presence of a fucose at position-3 was not tolerated by any of the enzymes assayed. 24362939 7 16 attach presence 948:955 arg2 fucose 962:967 a fucose 960:967 a fucose 960:967 The presence of a fucose at position-3 was not tolerated by any of the enzymes assayed. 24362939 6 17 theme three 894:898 arg1 factor 884:889 a factor 882:889 a factor of three 882:898 For Endo D the achievable synthetic efficiency was increased by a factor of three by the use a 3-O-benzyl protected acceptor. 24362939 3 18 theme decasaccharide 577:590 arg1 donors 602:607 penta- and decasaccharide oxazoline donors 566:607 penta- and decasaccharide oxazoline donors 566:607 Several different GlcNAc-asparagine acceptors were synthesised, and used in conjunction with penta- and decasaccharide oxazoline donors. 24362939 3 19 theme Several 473:479 arg1 acceptors 509:517 Several different GlcNAc-asparagine acceptors 473:517 Several different GlcNAc-asparagine acceptors 473:517 Several different GlcNAc-asparagine acceptors were synthesised, and used in conjunction with penta- and decasaccharide oxazoline donors. 24362939 4 20 theme Different 610:618 arg1 enzymes 620:626 Different enzymes 610:626 Different enzymes 610:626 Different enzymes showed different tolerances of modification of the GlcNAc acceptor. 24362939 2 21 theme synthetic 342:350 arg1 efficiency 352:361 The synthetic efficiency 338:361 The synthetic efficiency of a selection of family GH85 ENGases 338:399 The synthetic efficiency of a selection of family GH85 ENGases was investigated as the structure of the acceptor substrate was varied. 24362939 6 22 theme Endo 822:825 arg1 D 827:827 Endo D 822:827 Endo D 822:827 For Endo D the achievable synthetic efficiency was increased by a factor of three by the use a 3-O-benzyl protected acceptor. 24362939 2 23 theme substrate 451:459 arg1 structure 425:433 the structure 421:433 the structure of the acceptor substrate 421:459 The synthetic efficiency of a selection of family GH85 ENGases was investigated as the structure of the acceptor substrate was varied. 24362939 1 24 theme convergent 319:328 arg1 manner 330:335 a convergent manner 317:335 a convergent manner 317:335 Endo-β-N-Acetylglucosaminidases (ENGases) are highly useful biocatalysts that can be used to synthetically access a wide variety of defined homogenous N-linked glycoconjugates in a convergent manner. 24362939 5 25 theme Endo 768:771 arg1 M 773:773 Endo M 768:773 Endo M 768:773 Whilst none tolerated modification of either the 4- or 6-hydroxyl, both Endo M and Endo D tolerated modification of OH-3. 24362939 2 26 theme family 381:386 arg1 ENGases 393:399 family GH85 ENGases 381:399 family GH85 ENGases 381:399 The synthetic efficiency of a selection of family GH85 ENGases was investigated as the structure of the acceptor substrate was varied. 24362939 2 27 theme acceptor 442:449 arg1 substrate 451:459 the acceptor substrate 438:459 the acceptor substrate 438:459 The synthetic efficiency of a selection of family GH85 ENGases was investigated as the structure of the acceptor substrate was varied. 24362939 7 28 from position-3 972:981 arg1 presence 948:955 The presence 944:955 The presence of a fucose at position-3 944:981 The presence of a fucose at position-3 was not tolerated by any of the enzymes assayed. 24362939 3 29 theme different 481:489 arg1 acceptors 509:517 Several different GlcNAc-asparagine acceptors 473:517 Several different GlcNAc-asparagine acceptors 473:517 Several different GlcNAc-asparagine acceptors were synthesised, and used in conjunction with penta- and decasaccharide oxazoline donors. 24362939 5 30 dep 6-hydroxyl 751:760 arg1 either 734:739 either 734:739 either 734:739 Whilst none tolerated modification of either the 4- or 6-hydroxyl, both Endo M and Endo D tolerated modification of OH-3. 24362939 4 31 theme different 635:643 arg1 tolerances 645:654 different tolerances 635:654 different tolerances of modification of the GlcNAc acceptor 635:693 Different enzymes showed different tolerances of modification of the GlcNAc acceptor. 24362939 3 32 theme GlcNAc-asparagine 491:507 arg1 acceptors 509:517 Several different GlcNAc-asparagine acceptors 473:517 Several different GlcNAc-asparagine acceptors 473:517 Several different GlcNAc-asparagine acceptors were synthesised, and used in conjunction with penta- and decasaccharide oxazoline donors. 24362939 5 33 theme Endo 779:782 arg1 D 784:784 Endo D 779:784 Endo D 779:784 Whilst none tolerated modification of either the 4- or 6-hydroxyl, both Endo M and Endo D tolerated modification of OH-3. 24362939 5 34 theme 4- 745:746 arg1 or 748:749 or 748:749 or 748:749 Whilst none tolerated modification of either the 4- or 6-hydroxyl, both Endo M and Endo D tolerated modification of OH-3. 24362939 5 35 theme OH-3 812:815 arg1 modification 796:807 modification 796:807 modification of OH-3 796:815 Whilst none tolerated modification of either the 4- or 6-hydroxyl, both Endo M and Endo D tolerated modification of OH-3. 24362939 3 36 used used 541:544 arg2 acceptors 509:517 Several different GlcNAc-asparagine acceptors 473:517 Several different GlcNAc-asparagine acceptors 473:517 Several different GlcNAc-asparagine acceptors were synthesised, and used in conjunction with penta- and decasaccharide oxazoline donors. 24362939 1 37 from access 245:250 arg1 manner 330:335 a convergent manner 317:335 a convergent manner 317:335 Endo-β-N-Acetylglucosaminidases (ENGases) are highly useful biocatalysts that can be used to synthetically access a wide variety of defined homogenous N-linked glycoconjugates in a convergent manner. 24362939 0 38 theme enzymes 69:75 arg1 tolerance 56:64 tolerance 56:64 tolerance of enzymes to structural variation of the glycosyl amino acid acceptor 56:135 Endo-β-N-acetylglucosaminidase catalysed glycosylation: tolerance of enzymes to structural variation of the glycosyl amino acid acceptor. 24362939 6 39 dep use 907:909 arg1 acceptor 934:941 a 3-O-benzyl protected acceptor 911:941 the use a 3-O-benzyl protected acceptor 903:941 For Endo D the achievable synthetic efficiency was increased by a factor of three by the use a 3-O-benzyl protected acceptor. 24362939 5 40 theme or 748:749 arg1 6-hydroxyl 751:760 either the 4- or 6-hydroxyl 734:760 6-hydroxyl 751:760 Whilst none tolerated modification of either the 4- or 6-hydroxyl, both Endo M and Endo D tolerated modification of OH-3. 24362939 4 41 theme modification 659:670 arg1 tolerances 645:654 different tolerances 635:654 different tolerances of modification of the GlcNAc acceptor 635:693 Different enzymes showed different tolerances of modification of the GlcNAc acceptor. 24362939 1 42 used used 223:226 arg2 biocatalysts 198:209 highly useful biocatalysts 184:209 highly useful biocatalysts that can be used to synthetically access a wide variety of defined homogenous N-linked glycoconjugates in a convergent manner 184:335 Endo-β-N-Acetylglucosaminidases (ENGases) are highly useful biocatalysts that can be used to synthetically access a wide variety of defined homogenous N-linked glycoconjugates in a convergent manner. 24362939 1 42 used used 223:226 arg2 Endo-β-N-Acetylglucosaminidases 138:168 Endo-β-N-Acetylglucosaminidases 138:168 Endo-β-N-Acetylglucosaminidases (ENGases) 138:178 Endo-β-N-Acetylglucosaminidases (ENGases) are highly useful biocatalysts that can be used to synthetically access a wide variety of defined homogenous N-linked glycoconjugates in a convergent manner. 24362939 2 43 theme selection 368:376 arg1 efficiency 352:361 The synthetic efficiency 338:361 The synthetic efficiency of a selection of family GH85 ENGases 338:399 The synthetic efficiency of a selection of family GH85 ENGases was investigated as the structure of the acceptor substrate was varied. 24362939 7 44 theme fucose 962:967 arg1 presence 948:955 The presence 944:955 The presence of a fucose at position-3 944:981 The presence of a fucose at position-3 was not tolerated by any of the enzymes assayed. 24362939 5 45 theme 6-hydroxyl 751:760 arg1 modification 718:729 modification 718:729 modification of either the 4- or 6-hydroxyl 718:760 Whilst none tolerated modification of either the 4- or 6-hydroxyl, both Endo M and Endo D tolerated modification of OH-3. 24362939 6 46 theme achievable 833:842 arg1 efficiency 854:863 the achievable synthetic efficiency 829:863 the achievable synthetic efficiency 829:863 For Endo D the achievable synthetic efficiency was increased by a factor of three by the use a 3-O-benzyl protected acceptor. 24362939 3 47 theme penta- 566:571 arg1 donors 602:607 penta- and decasaccharide oxazoline donors 566:607 penta- and decasaccharide oxazoline donors 566:607 Several different GlcNAc-asparagine acceptors were synthesised, and used in conjunction with penta- and decasaccharide oxazoline donors. 24362939 1 48 theme wide 254:257 arg1 variety 259:265 a wide variety 252:265 a wide variety of defined homogenous N-linked glycoconjugates 252:312 Endo-β-N-Acetylglucosaminidases (ENGases) are highly useful biocatalysts that can be used to synthetically access a wide variety of defined homogenous N-linked glycoconjugates in a convergent manner. 24362939 1 48 theme wide 254:257 arg1 glycoconjugates 298:312 defined homogenous N-linked glycoconjugates 270:312 defined homogenous N-linked glycoconjugates 270:312 Endo-β-N-Acetylglucosaminidases (ENGases) are highly useful biocatalysts that can be used to synthetically access a wide variety of defined homogenous N-linked glycoconjugates in a convergent manner. 24362939 4 49 theme acceptor 686:693 arg1 modification 659:670 modification 659:670 modification of the GlcNAc acceptor 659:693 Different enzymes showed different tolerances of modification of the GlcNAc acceptor. 24362939 0 50 theme structural 80:89 arg1 variation 91:99 structural variation 80:99 structural variation of the glycosyl amino acid acceptor 80:135 Endo-β-N-acetylglucosaminidase catalysed glycosylation: tolerance of enzymes to structural variation of the glycosyl amino acid acceptor. 24362939 2 51 theme ENGases 393:399 arg1 selection 368:376 a selection 366:376 a selection of family GH85 ENGases 366:399 The synthetic efficiency of a selection of family GH85 ENGases was investigated as the structure of the acceptor substrate was varied. 24362939 4 52 theme GlcNAc 679:684 arg1 acceptor 686:693 the GlcNAc acceptor 675:693 the GlcNAc acceptor 675:693 Different enzymes showed different tolerances of modification of the GlcNAc acceptor. 25229868 4 0 theme lysozyme 487:494 arg1 G49N/D66H 503:511 an unstable lysozyme mutant G49N/D66H 475:511 an unstable lysozyme mutant G49N/D66H 475:511 The expression and secretion of an unstable lysozyme mutant G49N/D66H were enhanced and its intracellular localization was changed in the CNE1-deficient strain. 25229868 5 1 theme lysozyme 659:666 arg1 mutants 668:674 unstable lysozyme mutants 650:674 unstable lysozyme mutants (G49N/D66H, G49N/C76A, and K13D/G49N) 650:712 Furthermore, when Cne1p was co-expressed with unstable lysozyme mutants (G49N/D66H, G49N/C76A, and K13D/G49N), its affinity to the misfolded mutant proteins was revealed by co-immunoprecipitation. 25229868 5 1 theme lysozyme 659:666 arg1 G49N/C76A 688:696 G49N/C76A 688:696 G49N/C76A 688:696 Furthermore, when Cne1p was co-expressed with unstable lysozyme mutants (G49N/D66H, G49N/C76A, and K13D/G49N), its affinity to the misfolded mutant proteins was revealed by co-immunoprecipitation. 25229868 5 1 theme lysozyme 659:666 arg1 K13D/G49N 703:711 K13D/G49N 703:711 K13D/G49N 703:711 Furthermore, when Cne1p was co-expressed with unstable lysozyme mutants (G49N/D66H, G49N/C76A, and K13D/G49N), its affinity to the misfolded mutant proteins was revealed by co-immunoprecipitation. 25229868 5 1 theme lysozyme 659:666 arg1 G49N/D66H 677:685 G49N/D66H 677:685 G49N/D66H 677:685 Furthermore, when Cne1p was co-expressed with unstable lysozyme mutants (G49N/D66H, G49N/C76A, and K13D/G49N), its affinity to the misfolded mutant proteins was revealed by co-immunoprecipitation. 25229868 1 2 theme calnexin 148:155 arg1 Cne1p 120:124 Cne1p 120:124 Cne1p 120:124 Cne1p is a yeast homolog of calnexin, which is a constituent of endoplasmic reticulum (ER)-associated protein quality control system in mammals. 25229868 1 2 theme calnexin 148:155 arg1 constituent 169:179 a constituent 167:179 a constituent of endoplasmic reticulum (ER)-associated protein quality control system in mammals 167:262 Cne1p is a yeast homolog of calnexin, which is a constituent of endoplasmic reticulum (ER)-associated protein quality control system in mammals. 25229868 1 2 theme calnexin 148:155 arg1 homolog 137:143 a yeast homolog 129:143 a yeast homolog 129:143 Cne1p is a yeast homolog of calnexin, which is a constituent of endoplasmic reticulum (ER)-associated protein quality control system in mammals. 25229868 1 3 theme quality 230:236 arg1 system 246:251 endoplasmic reticulum (ER)-associated protein quality control system 184:251 endoplasmic reticulum (ER)-associated protein quality control system 184:251 Cne1p is a yeast homolog of calnexin, which is a constituent of endoplasmic reticulum (ER)-associated protein quality control system in mammals. 25229868 0 4 theme homolog 77:83 arg1 Cne1p 85:89 calnexin homolog Cne1p 68:89 calnexin homolog Cne1p 68:89 Unstable mutant lysozymes are degraded through the interaction with calnexin homolog Cne1p in Saccharomyces cerevisiae. 25229868 1 5 theme control 238:244 arg1 system 246:251 endoplasmic reticulum (ER)-associated protein quality control system 184:251 endoplasmic reticulum (ER)-associated protein quality control system 184:251 Cne1p is a yeast homolog of calnexin, which is a constituent of endoplasmic reticulum (ER)-associated protein quality control system in mammals. 25229868 0 6 theme Saccharomyces 94:106 arg1 cerevisiae 108:117 Saccharomyces cerevisiae 94:117 Saccharomyces cerevisiae 94:117 Unstable mutant lysozymes are degraded through the interaction with calnexin homolog Cne1p in Saccharomyces cerevisiae. 25229868 4 7 theme G49N/D66H 503:511 arg1 secretion 462:470 secretion 462:470 secretion 462:470 The expression and secretion of an unstable lysozyme mutant G49N/D66H were enhanced and its intracellular localization was changed in the CNE1-deficient strain. 25229868 4 7 theme G49N/D66H 503:511 arg1 expression 447:456 expression 447:456 expression 447:456 The expression and secretion of an unstable lysozyme mutant G49N/D66H were enhanced and its intracellular localization was changed in the CNE1-deficient strain. 25229868 2 8 from degradation 294:304 arg1 cerevisiae 346:355 Saccharomyces cerevisiae 332:355 Saccharomyces cerevisiae 332:355 Cne1p may be involved in the degradation of misfolded lysozymes in Saccharomyces cerevisiae. 25229868 1 9 theme system 246:251 arg1 Cne1p 120:124 Cne1p 120:124 Cne1p 120:124 Cne1p is a yeast homolog of calnexin, which is a constituent of endoplasmic reticulum (ER)-associated protein quality control system in mammals. 25229868 1 9 theme system 246:251 arg1 constituent 169:179 a constituent 167:179 a constituent of endoplasmic reticulum (ER)-associated protein quality control system in mammals 167:262 Cne1p is a yeast homolog of calnexin, which is a constituent of endoplasmic reticulum (ER)-associated protein quality control system in mammals. 25229868 1 9 theme system 246:251 arg1 homolog 137:143 a yeast homolog 129:143 a yeast homolog 129:143 Cne1p is a yeast homolog of calnexin, which is a constituent of endoplasmic reticulum (ER)-associated protein quality control system in mammals. 25229868 0 10 from interaction 51:61 arg1 cerevisiae 108:117 Saccharomyces cerevisiae 94:117 Saccharomyces cerevisiae 94:117 Unstable mutant lysozymes are degraded through the interaction with calnexin homolog Cne1p in Saccharomyces cerevisiae. 25229868 2 11 theme Saccharomyces 332:344 arg1 cerevisiae 346:355 Saccharomyces cerevisiae 332:355 Saccharomyces cerevisiae 332:355 Cne1p may be involved in the degradation of misfolded lysozymes in Saccharomyces cerevisiae. 25229868 6 12 theme N-glycosylation 890:904 arg1 tunicamycin 861:871 tunicamycin 861:871 tunicamycin 861:871 The interaction with Cne1p was abrogated by the addition of tunicamycin, an inhibitor of N-glycosylation, indicating that N-linked carbohydrates might be necessary for protein binding to Cne1p. 25229868 6 12 theme N-glycosylation 890:904 arg1 inhibitor 877:885 an inhibitor 874:885 an inhibitor of N-glycosylation 874:904 The interaction with Cne1p was abrogated by the addition of tunicamycin, an inhibitor of N-glycosylation, indicating that N-linked carbohydrates might be necessary for protein binding to Cne1p. 25229868 3 13 theme S. 428:429 arg1 cerevisiae 431:440 CNE1-deficient S. cerevisiae 413:440 CNE1-deficient S. cerevisiae 413:440 To test this, c-Myc-tagged lysozymes were expressed in CNE1-deficient S. cerevisiae. 25229868 5 14 theme misfolded 735:743 arg1 proteins 752:759 the misfolded mutant proteins 731:759 the misfolded mutant proteins 731:759 Furthermore, when Cne1p was co-expressed with unstable lysozyme mutants (G49N/D66H, G49N/C76A, and K13D/G49N), its affinity to the misfolded mutant proteins was revealed by co-immunoprecipitation. 25229868 4 15 theme unstable 478:485 arg1 G49N/D66H 503:511 an unstable lysozyme mutant G49N/D66H 475:511 an unstable lysozyme mutant G49N/D66H 475:511 The expression and secretion of an unstable lysozyme mutant G49N/D66H were enhanced and its intracellular localization was changed in the CNE1-deficient strain. 25229868 4 16 theme CNE1-deficient 581:594 arg1 strain 596:601 the CNE1-deficient strain 577:601 the CNE1-deficient strain 577:601 The expression and secretion of an unstable lysozyme mutant G49N/D66H were enhanced and its intracellular localization was changed in the CNE1-deficient strain. 25229868 6 17 with interaction 805:815 arg1 Cne1p 822:826 Cne1p 822:826 Cne1p 822:826 The interaction with Cne1p was abrogated by the addition of tunicamycin, an inhibitor of N-glycosylation, indicating that N-linked carbohydrates might be necessary for protein binding to Cne1p. 25229868 0 18 theme mutant 9:14 arg1 lysozymes 16:24 Unstable mutant lysozymes 0:24 Unstable mutant lysozymes 0:24 Unstable mutant lysozymes are degraded through the interaction with calnexin homolog Cne1p in Saccharomyces cerevisiae. 25229868 5 19 theme mutant 745:750 arg1 proteins 752:759 the misfolded mutant proteins 731:759 the misfolded mutant proteins 731:759 Furthermore, when Cne1p was co-expressed with unstable lysozyme mutants (G49N/D66H, G49N/C76A, and K13D/G49N), its affinity to the misfolded mutant proteins was revealed by co-immunoprecipitation. 25229868 0 20 theme Unstable 0:7 arg1 lysozymes 16:24 Unstable mutant lysozymes 0:24 Unstable mutant lysozymes 0:24 Unstable mutant lysozymes are degraded through the interaction with calnexin homolog Cne1p in Saccharomyces cerevisiae. 25229868 5 21 theme unstable 650:657 arg1 mutants 668:674 unstable lysozyme mutants 650:674 unstable lysozyme mutants (G49N/D66H, G49N/C76A, and K13D/G49N) 650:712 Furthermore, when Cne1p was co-expressed with unstable lysozyme mutants (G49N/D66H, G49N/C76A, and K13D/G49N), its affinity to the misfolded mutant proteins was revealed by co-immunoprecipitation. 25229868 5 21 theme unstable 650:657 arg1 G49N/C76A 688:696 G49N/C76A 688:696 G49N/C76A 688:696 Furthermore, when Cne1p was co-expressed with unstable lysozyme mutants (G49N/D66H, G49N/C76A, and K13D/G49N), its affinity to the misfolded mutant proteins was revealed by co-immunoprecipitation. 25229868 5 21 theme unstable 650:657 arg1 K13D/G49N 703:711 K13D/G49N 703:711 K13D/G49N 703:711 Furthermore, when Cne1p was co-expressed with unstable lysozyme mutants (G49N/D66H, G49N/C76A, and K13D/G49N), its affinity to the misfolded mutant proteins was revealed by co-immunoprecipitation. 25229868 5 21 theme unstable 650:657 arg1 G49N/D66H 677:685 G49N/D66H 677:685 G49N/D66H 677:685 Furthermore, when Cne1p was co-expressed with unstable lysozyme mutants (G49N/D66H, G49N/C76A, and K13D/G49N), its affinity to the misfolded mutant proteins was revealed by co-immunoprecipitation. 25229868 3 22 theme CNE1-deficient 413:426 arg1 cerevisiae 431:440 CNE1-deficient S. cerevisiae 413:440 CNE1-deficient S. cerevisiae 413:440 To test this, c-Myc-tagged lysozymes were expressed in CNE1-deficient S. cerevisiae. 25229868 7 23 from retention 1105:1113 arg1 ER 1122:1123 the ER 1118:1123 the ER 1118:1123 These results suggest that in yeasts, Cne1p interacts with misfolded lysozyme proteins possibly causing their retention in the ER and subsequent elimination via ER-associated degradation. 25229868 7 24 theme subsequent 1129:1138 arg1 elimination 1140:1150 subsequent elimination 1129:1150 subsequent elimination via ER-associated degradation 1129:1180 These results suggest that in yeasts, Cne1p interacts with misfolded lysozyme proteins possibly causing their retention in the ER and subsequent elimination via ER-associated degradation. 25229868 5 25 dep mutants 668:674 arg1 mutants 668:674 unstable lysozyme mutants 650:674 unstable lysozyme mutants (G49N/D66H, G49N/C76A, and K13D/G49N) 650:712 Furthermore, when Cne1p was co-expressed with unstable lysozyme mutants (G49N/D66H, G49N/C76A, and K13D/G49N), its affinity to the misfolded mutant proteins was revealed by co-immunoprecipitation. 25229868 5 25 dep mutants 668:674 arg1 G49N/C76A 688:696 G49N/C76A 688:696 G49N/C76A 688:696 Furthermore, when Cne1p was co-expressed with unstable lysozyme mutants (G49N/D66H, G49N/C76A, and K13D/G49N), its affinity to the misfolded mutant proteins was revealed by co-immunoprecipitation. 25229868 5 25 dep mutants 668:674 arg1 K13D/G49N 703:711 K13D/G49N 703:711 K13D/G49N 703:711 Furthermore, when Cne1p was co-expressed with unstable lysozyme mutants (G49N/D66H, G49N/C76A, and K13D/G49N), its affinity to the misfolded mutant proteins was revealed by co-immunoprecipitation. 25229868 5 25 dep mutants 668:674 arg1 G49N/D66H 677:685 G49N/D66H 677:685 G49N/D66H 677:685 Furthermore, when Cne1p was co-expressed with unstable lysozyme mutants (G49N/D66H, G49N/C76A, and K13D/G49N), its affinity to the misfolded mutant proteins was revealed by co-immunoprecipitation. 25229868 6 26 theme N-linked 923:930 arg1 carbohydrates 932:944 N-linked carbohydrates 923:944 N-linked carbohydrates 923:944 The interaction with Cne1p was abrogated by the addition of tunicamycin, an inhibitor of N-glycosylation, indicating that N-linked carbohydrates might be necessary for protein binding to Cne1p. 25229868 1 27 theme endoplasmic 184:194 arg1 ER 207:208 ER 207:208 ER 207:208 Cne1p is a yeast homolog of calnexin, which is a constituent of endoplasmic reticulum (ER)-associated protein quality control system in mammals. 25229868 1 27 theme endoplasmic 184:194 arg1 reticulum 196:204 endoplasmic reticulum 184:204 endoplasmic reticulum (ER) 184:209 Cne1p is a yeast homolog of calnexin, which is a constituent of endoplasmic reticulum (ER)-associated protein quality control system in mammals. 25229868 6 28 theme protein 969:975 arg1 binding 977:983 protein binding 969:983 protein binding to Cne1p 969:992 The interaction with Cne1p was abrogated by the addition of tunicamycin, an inhibitor of N-glycosylation, indicating that N-linked carbohydrates might be necessary for protein binding to Cne1p. 25229868 7 29 theme lysozyme 1064:1071 arg1 proteins 1073:1080 misfolded lysozyme proteins 1054:1080 misfolded lysozyme proteins 1054:1080 These results suggest that in yeasts, Cne1p interacts with misfolded lysozyme proteins possibly causing their retention in the ER and subsequent elimination via ER-associated degradation. 25229868 6 30 link N-linked 923:930 arg1 carbohydrates 932:944 N-linked carbohydrates 923:944 N-linked carbohydrates 923:944 The interaction with Cne1p was abrogated by the addition of tunicamycin, an inhibitor of N-glycosylation, indicating that N-linked carbohydrates might be necessary for protein binding to Cne1p. 25229868 6 31 theme tunicamycin 861:871 arg1 addition 849:856 the addition 845:856 the addition of tunicamycin, an inhibitor of N-glycosylation 845:904 The interaction with Cne1p was abrogated by the addition of tunicamycin, an inhibitor of N-glycosylation, indicating that N-linked carbohydrates might be necessary for protein binding to Cne1p. 25229868 3 32 theme c-Myc-tagged 372:383 arg1 lysozymes 385:393 c-Myc-tagged lysozymes 372:393 c-Myc-tagged lysozymes 372:393 To test this, c-Myc-tagged lysozymes were expressed in CNE1-deficient S. cerevisiae. 25229868 2 33 theme lysozymes 319:327 arg1 degradation 294:304 the degradation 290:304 the degradation of misfolded lysozymes in Saccharomyces cerevisiae 290:355 Cne1p may be involved in the degradation of misfolded lysozymes in Saccharomyces cerevisiae. 25229868 7 34 theme ER-associated 1156:1168 arg1 degradation 1170:1180 ER-associated degradation 1156:1180 ER-associated degradation 1156:1180 These results suggest that in yeasts, Cne1p interacts with misfolded lysozyme proteins possibly causing their retention in the ER and subsequent elimination via ER-associated degradation. 25229868 4 35 theme intracellular 535:547 arg1 localization 549:560 its intracellular localization 531:560 its intracellular localization 531:560 The expression and secretion of an unstable lysozyme mutant G49N/D66H were enhanced and its intracellular localization was changed in the CNE1-deficient strain. 25229868 7 36 theme misfolded 1054:1062 arg1 proteins 1073:1080 misfolded lysozyme proteins 1054:1080 misfolded lysozyme proteins 1054:1080 These results suggest that in yeasts, Cne1p interacts with misfolded lysozyme proteins possibly causing their retention in the ER and subsequent elimination via ER-associated degradation. 25229868 2 37 theme misfolded 309:317 arg1 lysozymes 319:327 misfolded lysozymes 309:327 misfolded lysozymes 309:327 Cne1p may be involved in the degradation of misfolded lysozymes in Saccharomyces cerevisiae. 25229868 7 38 from elimination 1140:1150 arg1 ER 1122:1123 the ER 1118:1123 the ER 1118:1123 These results suggest that in yeasts, Cne1p interacts with misfolded lysozyme proteins possibly causing their retention in the ER and subsequent elimination via ER-associated degradation. 25229868 0 39 with interaction 51:61 arg1 Cne1p 85:89 calnexin homolog Cne1p 68:89 calnexin homolog Cne1p 68:89 Unstable mutant lysozymes are degraded through the interaction with calnexin homolog Cne1p in Saccharomyces cerevisiae. 25229868 1 40 theme yeast 131:135 arg1 Cne1p 120:124 Cne1p 120:124 Cne1p 120:124 Cne1p is a yeast homolog of calnexin, which is a constituent of endoplasmic reticulum (ER)-associated protein quality control system in mammals. 25229868 1 40 theme yeast 131:135 arg1 constituent 169:179 a constituent 167:179 a constituent of endoplasmic reticulum (ER)-associated protein quality control system in mammals 167:262 Cne1p is a yeast homolog of calnexin, which is a constituent of endoplasmic reticulum (ER)-associated protein quality control system in mammals. 25229868 1 40 theme yeast 131:135 arg1 homolog 137:143 a yeast homolog 129:143 a yeast homolog 129:143 Cne1p is a yeast homolog of calnexin, which is a constituent of endoplasmic reticulum (ER)-associated protein quality control system in mammals. 25229868 0 41 theme calnexin 68:75 arg1 Cne1p 85:89 calnexin homolog Cne1p 68:89 calnexin homolog Cne1p 68:89 Unstable mutant lysozymes are degraded through the interaction with calnexin homolog Cne1p in Saccharomyces cerevisiae. 25229868 1 42 from constituent 169:179 arg1 mammals 256:262 mammals 256:262 mammals 256:262 Cne1p is a yeast homolog of calnexin, which is a constituent of endoplasmic reticulum (ER)-associated protein quality control system in mammals. 25229868 1 43 theme -associated 210:220 arg1 system 246:251 endoplasmic reticulum (ER)-associated protein quality control system 184:251 endoplasmic reticulum (ER)-associated protein quality control system 184:251 Cne1p is a yeast homolog of calnexin, which is a constituent of endoplasmic reticulum (ER)-associated protein quality control system in mammals. 25229868 4 44 theme mutant 496:501 arg1 G49N/D66H 503:511 an unstable lysozyme mutant G49N/D66H 475:511 an unstable lysozyme mutant G49N/D66H 475:511 The expression and secretion of an unstable lysozyme mutant G49N/D66H were enhanced and its intracellular localization was changed in the CNE1-deficient strain. 25229868 1 45 theme protein 222:228 arg1 system 246:251 endoplasmic reticulum (ER)-associated protein quality control system 184:251 endoplasmic reticulum (ER)-associated protein quality control system 184:251 Cne1p is a yeast homolog of calnexin, which is a constituent of endoplasmic reticulum (ER)-associated protein quality control system in mammals. 25660292 4 0 theme morphological 501:513 arg1 observation 515:525 morphological observation 501:525 morphological observation by electron microscopy 501:548 Content determination by high-performance liquid chromatography (HPLC) and spectrophotometry, enzyme activity determination by colorimetry, and morphological observation by electron microscopy were performed in the present study. 25660292 8 1 dep equation 1215:1222 arg1 0.000 1279:1283 0.000 964 1279:1287 correlation equation: Y = - 0.625 4 + 0.020 84 × X3 + 0.001 514 × X1 × X2 - 0.000 964 4 × X2 × X3 1203:1299 The relationship between the storage factors and degree of browning (Y) could be described by following correlation equation: Y = - 0.625 4 + 0.020 84 × X3 + 0.001 514 × X1 × X2 - 0.000 964 4 × X2 × X3. 25660292 8 1 dep equation 1215:1222 arg1 Y 1225:1225 Y 1225:1225 correlation equation: Y = - 0.625 4 + 0.020 84 × X3 + 0.001 514 × X1 × X2 - 0.000 964 4 × X2 × X3 1203:1299 The relationship between the storage factors and degree of browning (Y) could be described by following correlation equation: Y = - 0.625 4 + 0.020 84 × X3 + 0.001 514 × X1 × X2 - 0.000 964 4 × X2 × X3. 25660292 6 2 theme Radix 757:761 arg1 Ophiopogonis 763:774 browned Radix Ophiopogonis 749:774 browned Radix Ophiopogonis 749:774 The cortex cell wall of browned Radix Ophiopogonis was ruptured. 25660292 1 3 theme potential 135:143 arg1 risk 145:148 potential risk 135:148 potential risk 135:148 In the storage of Radix Ophiopogonis, browning often happens to cause potential risk with regard to safety. 25660292 10 4 theme wall 1484:1487 arg1 rupture 1457:1463 the rupture 1453:1463 the rupture of the cortex cell wall 1453:1487 Following the activation of cellulase, the rupture of the cortex cell wall and the outflow of cell substances flowed out, which caused the Radix Ophiopogonis tissue to become soft and sticky. 25660292 10 4 theme wall 1484:1487 arg1 outflow 1497:1503 the outflow 1493:1503 the outflow of cell substances 1493:1522 Following the activation of cellulase, the rupture of the cortex cell wall and the outflow of cell substances flowed out, which caused the Radix Ophiopogonis tissue to become soft and sticky. 25660292 3 5 theme browning 295:302 arg1 mechanisms 277:286 mechanisms 277:286 mechanisms 277:286 In this research, the causes and mechanisms of the browning of Radix Ophiopogonis were preliminarily elucidated. 25660292 3 5 theme browning 295:302 arg1 causes 266:271 causes 266:271 causes 266:271 In this research, the causes and mechanisms of the browning of Radix Ophiopogonis were preliminarily elucidated. 25660292 4 6 theme electron 530:537 arg1 microscopy 539:548 electron microscopy 530:548 electron microscopy 530:548 Content determination by high-performance liquid chromatography (HPLC) and spectrophotometry, enzyme activity determination by colorimetry, and morphological observation by electron microscopy were performed in the present study. 25660292 4 7 theme liquid 399:404 arg1 HPLC 422:425 HPLC 422:425 HPLC 422:425 Content determination by high-performance liquid chromatography (HPLC) and spectrophotometry, enzyme activity determination by colorimetry, and morphological observation by electron microscopy were performed in the present study. 25660292 4 7 theme liquid 399:404 arg1 chromatography 406:419 high-performance liquid chromatography 382:419 high-performance liquid chromatography (HPLC) 382:426 Content determination by high-performance liquid chromatography (HPLC) and spectrophotometry, enzyme activity determination by colorimetry, and morphological observation by electron microscopy were performed in the present study. 25660292 8 8 theme × 1291:1291 arg1 X3 1298:1299 4 × X2 × X3 1289:1299 correlation equation: Y = - 0.625 4 + 0.020 84 × X3 + 0.001 514 × X1 × X2 - 0.000 964 4 × X2 × X3 1203:1299 The relationship between the storage factors and degree of browning (Y) could be described by following correlation equation: Y = - 0.625 4 + 0.020 84 × X3 + 0.001 514 × X1 × X2 - 0.000 964 4 × X2 × X3. 25660292 10 9 theme cell 1508:1511 arg1 substances 1513:1522 cell substances 1508:1522 cell substances 1508:1522 Following the activation of cellulase, the rupture of the cortex cell wall and the outflow of cell substances flowed out, which caused the Radix Ophiopogonis tissue to become soft and sticky. 25660292 11 10 theme browning 1629:1636 arg1 production 1647:1656 the production 1643:1656 the production of 5-HMF 1643:1665 The main causes of the browning were the production of 5-HMF, the activation of polyphenol oxidase, Maillard reactions and enzymatic browning. 25660292 11 10 theme browning 1629:1636 arg1 causes 1615:1620 The main causes 1606:1620 The main causes of the browning 1606:1636 The main causes of the browning were the production of 5-HMF, the activation of polyphenol oxidase, Maillard reactions and enzymatic browning. 25660292 3 11 dep causes 266:271 arg1 the 262:264 the 262:264 the 262:264 In this research, the causes and mechanisms of the browning of Radix Ophiopogonis were preliminarily elucidated. 25660292 7 12 theme sugars 966:971 arg1 levels 896:901 the levels 892:901 the levels of 5-hydroxymethylfurfural (5-HMF), total sugars, and reducing sugars 892:971 Compared with the normal Radix Ophiopogonis, cellulase and polyphenol oxidase enzymes were activated, the levels of 5-hydroxymethylfurfural (5-HMF), total sugars, and reducing sugars were increased, while the levels of polysaccharides and methylophiopogonanone A were decreased in browned Radix Ophiopogonis. 25660292 4 13 theme high-performance 382:397 arg1 HPLC 422:425 HPLC 422:425 HPLC 422:425 Content determination by high-performance liquid chromatography (HPLC) and spectrophotometry, enzyme activity determination by colorimetry, and morphological observation by electron microscopy were performed in the present study. 25660292 4 13 theme high-performance 382:397 arg1 chromatography 406:419 high-performance liquid chromatography 382:419 high-performance liquid chromatography (HPLC) 382:426 Content determination by high-performance liquid chromatography (HPLC) and spectrophotometry, enzyme activity determination by colorimetry, and morphological observation by electron microscopy were performed in the present study. 25660292 7 14 theme polysaccharides 1009:1023 arg1 levels 999:1004 the levels 995:1004 the levels of polysaccharides and methylophiopogonanone A 995:1051 Compared with the normal Radix Ophiopogonis, cellulase and polyphenol oxidase enzymes were activated, the levels of 5-hydroxymethylfurfural (5-HMF), total sugars, and reducing sugars were increased, while the levels of polysaccharides and methylophiopogonanone A were decreased in browned Radix Ophiopogonis. 25660292 11 15 theme polyphenol 1686:1695 arg1 oxidase 1697:1703 polyphenol oxidase 1686:1703 polyphenol oxidase 1686:1703 The main causes of the browning were the production of 5-HMF, the activation of polyphenol oxidase, Maillard reactions and enzymatic browning. 25660292 11 16 theme main 1610:1613 arg1 production 1647:1656 the production 1643:1656 the production of 5-HMF 1643:1665 The main causes of the browning were the production of 5-HMF, the activation of polyphenol oxidase, Maillard reactions and enzymatic browning. 25660292 11 16 theme main 1610:1613 arg1 causes 1615:1620 The main causes 1606:1620 The main causes of the browning 1606:1636 The main causes of the browning were the production of 5-HMF, the activation of polyphenol oxidase, Maillard reactions and enzymatic browning. 25660292 5 17 theme storage 708:714 arg1 factors 716:722 storage factors 708:722 storage factors 708:722 Uniform design and three-dimensional response surfaces were applied to investigate the relationship between browning and storage factors. 25660292 8 18 theme X2 1293:1294 arg1 X3 1298:1299 4 × X2 × X3 1289:1299 correlation equation: Y = - 0.625 4 + 0.020 84 × X3 + 0.001 514 × X1 × X2 - 0.000 964 4 × X2 × X3 1203:1299 The relationship between the storage factors and degree of browning (Y) could be described by following correlation equation: Y = - 0.625 4 + 0.020 84 × X3 + 0.001 514 × X1 × X2 - 0.000 964 4 × X2 × X3. 25660292 6 19 theme browned 749:755 arg1 Ophiopogonis 763:774 browned Radix Ophiopogonis 749:774 browned Radix Ophiopogonis 749:774 The cortex cell wall of browned Radix Ophiopogonis was ruptured. 25660292 9 20 theme Ophiopogonis 1388:1399 arg1 composition 1367:1377 the chemical composition 1354:1377 the chemical composition of Radix Ophiopogonis 1354:1399 Accompanied with browning under storage conditions, the chemical composition of Radix Ophiopogonis was altered. 25660292 3 21 theme Ophiopogonis 313:324 arg1 browning 295:302 the browning 291:302 the browning of Radix Ophiopogonis 291:324 In this research, the causes and mechanisms of the browning of Radix Ophiopogonis were preliminarily elucidated. 25660292 10 22 theme cellulase 1442:1450 arg1 activation 1428:1437 the activation 1424:1437 the activation of cellulase 1424:1450 Following the activation of cellulase, the rupture of the cortex cell wall and the outflow of cell substances flowed out, which caused the Radix Ophiopogonis tissue to become soft and sticky. 25660292 8 23 theme × 1296:1296 arg1 X3 1298:1299 4 × X2 × X3 1289:1299 correlation equation: Y = - 0.625 4 + 0.020 84 × X3 + 0.001 514 × X1 × X2 - 0.000 964 4 × X2 × X3 1203:1299 The relationship between the storage factors and degree of browning (Y) could be described by following correlation equation: Y = - 0.625 4 + 0.020 84 × X3 + 0.001 514 × X1 × X2 - 0.000 964 4 × X2 × X3. 25660292 7 24 theme 5-hydroxymethylfurfural 906:928 arg1 levels 896:901 the levels 892:901 the levels of 5-hydroxymethylfurfural (5-HMF), total sugars, and reducing sugars 892:971 Compared with the normal Radix Ophiopogonis, cellulase and polyphenol oxidase enzymes were activated, the levels of 5-hydroxymethylfurfural (5-HMF), total sugars, and reducing sugars were increased, while the levels of polysaccharides and methylophiopogonanone A were decreased in browned Radix Ophiopogonis. 25660292 8 25 theme × 1250:1250 arg1 X3 1252:1253 0.625 4 + 0.020 84 × X3 1231:1253 0.625 4 + 0.020 84 × X3 1231:1253 The relationship between the storage factors and degree of browning (Y) could be described by following correlation equation: Y = - 0.625 4 + 0.020 84 × X3 + 0.001 514 × X1 × X2 - 0.000 964 4 × X2 × X3. 25660292 8 26 theme correlation 1203:1213 arg1 equation 1215:1222 correlation equation 1203:1222 correlation equation: Y = - 0.625 4 + 0.020 84 × X3 + 0.001 514 × X1 × X2 - 0.000 964 4 × X2 × X3 1203:1299 The relationship between the storage factors and degree of browning (Y) could be described by following correlation equation: Y = - 0.625 4 + 0.020 84 × X3 + 0.001 514 × X1 × X2 - 0.000 964 4 × X2 × X3. 25660292 10 27 theme Radix 1553:1557 arg1 tissue 1572:1577 the Radix Ophiopogonis tissue 1549:1577 the Radix Ophiopogonis tissue 1549:1577 Following the activation of cellulase, the rupture of the cortex cell wall and the outflow of cell substances flowed out, which caused the Radix Ophiopogonis tissue to become soft and sticky. 25660292 5 28 theme Uniform 587:593 arg1 design 595:600 Uniform design 587:600 Uniform design 587:600 Uniform design and three-dimensional response surfaces were applied to investigate the relationship between browning and storage factors. 25660292 11 29 theme Maillard 1706:1713 arg1 reactions 1715:1723 Maillard reactions 1706:1723 Maillard reactions 1706:1723 The main causes of the browning were the production of 5-HMF, the activation of polyphenol oxidase, Maillard reactions and enzymatic browning. 25660292 8 30 theme 84 1247:1248 arg1 × 1250:1250 × 1250:1250 × 1250:1250 The relationship between the storage factors and degree of browning (Y) could be described by following correlation equation: Y = - 0.625 4 + 0.020 84 × X3 + 0.001 514 × X1 × X2 - 0.000 964 4 × X2 × X3. 25660292 7 31 theme polyphenol 849:858 arg1 oxidase 860:866 polyphenol oxidase 849:866 polyphenol oxidase 849:866 Compared with the normal Radix Ophiopogonis, cellulase and polyphenol oxidase enzymes were activated, the levels of 5-hydroxymethylfurfural (5-HMF), total sugars, and reducing sugars were increased, while the levels of polysaccharides and methylophiopogonanone A were decreased in browned Radix Ophiopogonis. 25660292 6 32 theme cell 736:739 arg1 wall 741:744 The cortex cell wall 725:744 The cortex cell wall of browned Radix Ophiopogonis 725:774 The cortex cell wall of browned Radix Ophiopogonis was ruptured. 25660292 4 33 theme present 572:578 arg1 study 580:584 the present study 568:584 the present study 568:584 Content determination by high-performance liquid chromatography (HPLC) and spectrophotometry, enzyme activity determination by colorimetry, and morphological observation by electron microscopy were performed in the present study. 25660292 7 34 theme reducing 957:964 arg1 sugars 966:971 reducing sugars 957:971 reducing sugars 957:971 Compared with the normal Radix Ophiopogonis, cellulase and polyphenol oxidase enzymes were activated, the levels of 5-hydroxymethylfurfural (5-HMF), total sugars, and reducing sugars were increased, while the levels of polysaccharides and methylophiopogonanone A were decreased in browned Radix Ophiopogonis. 25660292 6 35 theme cortex 729:734 arg1 wall 741:744 The cortex cell wall 725:744 The cortex cell wall of browned Radix Ophiopogonis 725:774 The cortex cell wall of browned Radix Ophiopogonis was ruptured. 25660292 7 36 theme oxidase 860:866 arg1 enzymes 868:874 cellulase and polyphenol oxidase enzymes 835:874 cellulase and polyphenol oxidase enzymes 835:874 Compared with the normal Radix Ophiopogonis, cellulase and polyphenol oxidase enzymes were activated, the levels of 5-hydroxymethylfurfural (5-HMF), total sugars, and reducing sugars were increased, while the levels of polysaccharides and methylophiopogonanone A were decreased in browned Radix Ophiopogonis. 25660292 12 37 theme relative 1802:1809 arg1 HR 1821:1822 HR 1821:1822 HR 1821:1822 Browning could be effectively prevented when the air relative humidity (HR), temperature, and moisture content were under 25% RH, 12 °C and 18%, respectively. 25660292 12 37 theme relative 1802:1809 arg1 humidity 1811:1818 the air relative humidity 1794:1818 the air relative humidity (HR) 1794:1823 Browning could be effectively prevented when the air relative humidity (HR), temperature, and moisture content were under 25% RH, 12 °C and 18%, respectively. 25660292 5 38 theme three-dimensional 606:622 arg1 surfaces 633:640 three-dimensional response surfaces 606:640 three-dimensional response surfaces 606:640 Uniform design and three-dimensional response surfaces were applied to investigate the relationship between browning and storage factors. 25660292 5 39 theme response 624:631 arg1 surfaces 633:640 three-dimensional response surfaces 606:640 three-dimensional response surfaces 606:640 Uniform design and three-dimensional response surfaces were applied to investigate the relationship between browning and storage factors. 25660292 8 40 theme 514 1263:1265 arg1 X2 1274:1275 0.001 514 × X1 × X2 1257:1275 0.001 514 × X1 × X2 1257:1275 The relationship between the storage factors and degree of browning (Y) could be described by following correlation equation: Y = - 0.625 4 + 0.020 84 × X3 + 0.001 514 × X1 × X2 - 0.000 964 4 × X2 × X3. 25660292 8 41 theme = 1227:1227 arg1 Y 1225:1225 Y 1225:1225 correlation equation: Y = - 0.625 4 + 0.020 84 × X3 + 0.001 514 × X1 × X2 - 0.000 964 4 × X2 × X3 1203:1299 The relationship between the storage factors and degree of browning (Y) could be described by following correlation equation: Y = - 0.625 4 + 0.020 84 × X3 + 0.001 514 × X1 × X2 - 0.000 964 4 × X2 × X3. 25660292 7 42 theme cellulase 835:843 arg1 enzymes 868:874 cellulase and polyphenol oxidase enzymes 835:874 cellulase and polyphenol oxidase enzymes 835:874 Compared with the normal Radix Ophiopogonis, cellulase and polyphenol oxidase enzymes were activated, the levels of 5-hydroxymethylfurfural (5-HMF), total sugars, and reducing sugars were increased, while the levels of polysaccharides and methylophiopogonanone A were decreased in browned Radix Ophiopogonis. 25660292 8 43 theme storage 1128:1134 arg1 factors 1136:1142 the storage factors 1124:1142 the storage factors 1124:1142 The relationship between the storage factors and degree of browning (Y) could be described by following correlation equation: Y = - 0.625 4 + 0.020 84 × X3 + 0.001 514 × X1 × X2 - 0.000 964 4 × X2 × X3. 25660292 4 44 theme enzyme 451:456 arg1 determination 467:479 enzyme activity determination 451:479 enzyme activity determination by colorimetry 451:494 Content determination by high-performance liquid chromatography (HPLC) and spectrophotometry, enzyme activity determination by colorimetry, and morphological observation by electron microscopy were performed in the present study. 25660292 1 45 theme Ophiopogonis 89:100 arg1 storage 72:78 the storage 68:78 the storage of Radix Ophiopogonis 68:100 In the storage of Radix Ophiopogonis, browning often happens to cause potential risk with regard to safety. 25660292 8 46 theme 0.001 1257:1261 arg1 514 1263:1265 514 1263:1265 514 1263:1265 The relationship between the storage factors and degree of browning (Y) could be described by following correlation equation: Y = - 0.625 4 + 0.020 84 × X3 + 0.001 514 × X1 × X2 - 0.000 964 4 × X2 × X3. 25660292 0 47 theme Ophiopogonis 27:38 arg1 browning 40:47 Radix Ophiopogonis browning 21:47 Radix Ophiopogonis browning 21:47 Cause and control of Radix Ophiopogonis browning during storage. 25660292 8 48 theme X1 1269:1270 arg1 X2 1274:1275 0.001 514 × X1 × X2 1257:1275 0.001 514 × X1 × X2 1257:1275 The relationship between the storage factors and degree of browning (Y) could be described by following correlation equation: Y = - 0.625 4 + 0.020 84 × X3 + 0.001 514 × X1 × X2 - 0.000 964 4 × X2 × X3. 25660292 0 49 theme Radix 21:25 arg1 browning 40:47 Radix Ophiopogonis browning 21:47 Radix Ophiopogonis browning 21:47 Cause and control of Radix Ophiopogonis browning during storage. 25660292 9 50 theme storage 1334:1340 arg1 conditions 1342:1351 storage conditions 1334:1351 storage conditions 1334:1351 Accompanied with browning under storage conditions, the chemical composition of Radix Ophiopogonis was altered. 25660292 7 51 theme Radix 815:819 arg1 Ophiopogonis 821:832 the normal Radix Ophiopogonis 804:832 the normal Radix Ophiopogonis 804:832 Compared with the normal Radix Ophiopogonis, cellulase and polyphenol oxidase enzymes were activated, the levels of 5-hydroxymethylfurfural (5-HMF), total sugars, and reducing sugars were increased, while the levels of polysaccharides and methylophiopogonanone A were decreased in browned Radix Ophiopogonis. 25660292 10 52 theme Ophiopogonis 1559:1570 arg1 tissue 1572:1577 the Radix Ophiopogonis tissue 1549:1577 the Radix Ophiopogonis tissue 1549:1577 Following the activation of cellulase, the rupture of the cortex cell wall and the outflow of cell substances flowed out, which caused the Radix Ophiopogonis tissue to become soft and sticky. 25660292 8 53 theme browning 1158:1165 arg1 relationship 1103:1114 The relationship 1099:1114 The relationship between the storage factors 1099:1142 The relationship between the storage factors and degree of browning (Y) could be described by following correlation equation: Y = - 0.625 4 + 0.020 84 × X3 + 0.001 514 × X1 × X2 - 0.000 964 4 × X2 × X3. 25660292 8 53 theme browning 1158:1165 arg1 degree 1148:1153 degree 1148:1153 degree of browning (Y) 1148:1169 The relationship between the storage factors and degree of browning (Y) could be described by following correlation equation: Y = - 0.625 4 + 0.020 84 × X3 + 0.001 514 × X1 × X2 - 0.000 964 4 × X2 × X3. 25660292 4 54 theme activity 458:465 arg1 determination 467:479 enzyme activity determination 451:479 enzyme activity determination by colorimetry 451:494 Content determination by high-performance liquid chromatography (HPLC) and spectrophotometry, enzyme activity determination by colorimetry, and morphological observation by electron microscopy were performed in the present study. 25660292 10 55 theme cortex 1472:1477 arg1 wall 1484:1487 the cortex cell wall 1468:1487 the cortex cell wall 1468:1487 Following the activation of cellulase, the rupture of the cortex cell wall and the outflow of cell substances flowed out, which caused the Radix Ophiopogonis tissue to become soft and sticky. 25660292 10 56 theme cell 1479:1482 arg1 wall 1484:1487 the cortex cell wall 1468:1487 the cortex cell wall 1468:1487 Following the activation of cellulase, the rupture of the cortex cell wall and the outflow of cell substances flowed out, which caused the Radix Ophiopogonis tissue to become soft and sticky. 25660292 0 57 theme browning 40:47 arg1 control 10:16 control 10:16 control 10:16 Cause and control of Radix Ophiopogonis browning during storage. 25660292 0 57 theme browning 40:47 arg1 Cause 0:4 Cause 0:4 Cause 0:4 Cause and control of Radix Ophiopogonis browning during storage. 25660292 7 58 theme normal 808:813 arg1 Ophiopogonis 821:832 the normal Radix Ophiopogonis 804:832 the normal Radix Ophiopogonis 804:832 Compared with the normal Radix Ophiopogonis, cellulase and polyphenol oxidase enzymes were activated, the levels of 5-hydroxymethylfurfural (5-HMF), total sugars, and reducing sugars were increased, while the levels of polysaccharides and methylophiopogonanone A were decreased in browned Radix Ophiopogonis. 25660292 8 59 dep = 1227:1227 arg1 X3 1252:1253 0.625 4 + 0.020 84 × X3 1231:1253 0.625 4 + 0.020 84 × X3 1231:1253 The relationship between the storage factors and degree of browning (Y) could be described by following correlation equation: Y = - 0.625 4 + 0.020 84 × X3 + 0.001 514 × X1 × X2 - 0.000 964 4 × X2 × X3. 25660292 8 59 dep = 1227:1227 arg1 X2 1274:1275 0.001 514 × X1 × X2 1257:1275 0.001 514 × X1 × X2 1257:1275 The relationship between the storage factors and degree of browning (Y) could be described by following correlation equation: Y = - 0.625 4 + 0.020 84 × X3 + 0.001 514 × X1 × X2 - 0.000 964 4 × X2 × X3. 25660292 11 60 theme 5-HMF 1661:1665 arg1 activation 1672:1681 the activation 1668:1681 the activation of polyphenol oxidase 1668:1703 The main causes of the browning were the production of 5-HMF, the activation of polyphenol oxidase, Maillard reactions and enzymatic browning. 25660292 11 60 theme 5-HMF 1661:1665 arg1 production 1647:1656 the production 1643:1656 the production of 5-HMF 1643:1665 The main causes of the browning were the production of 5-HMF, the activation of polyphenol oxidase, Maillard reactions and enzymatic browning. 25660292 11 60 theme 5-HMF 1661:1665 arg1 reactions 1715:1723 Maillard reactions 1706:1723 Maillard reactions 1706:1723 The main causes of the browning were the production of 5-HMF, the activation of polyphenol oxidase, Maillard reactions and enzymatic browning. 25660292 11 60 theme 5-HMF 1661:1665 arg1 browning 1739:1746 enzymatic browning 1729:1746 enzymatic browning 1729:1746 The main causes of the browning were the production of 5-HMF, the activation of polyphenol oxidase, Maillard reactions and enzymatic browning. 25660292 11 60 theme 5-HMF 1661:1665 arg1 causes 1615:1620 The main causes 1606:1620 The main causes of the browning 1606:1636 The main causes of the browning were the production of 5-HMF, the activation of polyphenol oxidase, Maillard reactions and enzymatic browning. 25660292 7 61 theme A 1051:1051 arg1 levels 999:1004 the levels 995:1004 the levels of polysaccharides and methylophiopogonanone A 995:1051 Compared with the normal Radix Ophiopogonis, cellulase and polyphenol oxidase enzymes were activated, the levels of 5-hydroxymethylfurfural (5-HMF), total sugars, and reducing sugars were increased, while the levels of polysaccharides and methylophiopogonanone A were decreased in browned Radix Ophiopogonis. 25660292 8 62 theme × 1272:1272 arg1 X2 1274:1275 0.001 514 × X1 × X2 1257:1275 0.001 514 × X1 × X2 1257:1275 The relationship between the storage factors and degree of browning (Y) could be described by following correlation equation: Y = - 0.625 4 + 0.020 84 × X3 + 0.001 514 × X1 × X2 - 0.000 964 4 × X2 × X3. 25660292 4 63 theme Content 357:363 arg1 determination 365:377 Content determination 357:377 Content determination by high-performance liquid chromatography (HPLC) and spectrophotometry 357:448 Content determination by high-performance liquid chromatography (HPLC) and spectrophotometry, enzyme activity determination by colorimetry, and morphological observation by electron microscopy were performed in the present study. 25660292 7 64 theme browned 1071:1077 arg1 Ophiopogonis 1085:1096 browned Radix Ophiopogonis 1071:1096 browned Radix Ophiopogonis 1071:1096 Compared with the normal Radix Ophiopogonis, cellulase and polyphenol oxidase enzymes were activated, the levels of 5-hydroxymethylfurfural (5-HMF), total sugars, and reducing sugars were increased, while the levels of polysaccharides and methylophiopogonanone A were decreased in browned Radix Ophiopogonis. 25660292 2 65 theme few 184:186 arg1 reports 188:194 Previously few reports 173:194 Previously few reports 173:194 Previously few reports investigate the browning of Radix Ophiopogonis. 25660292 8 66 dep 0.000 1279:1283 arg1 X3 1298:1299 4 × X2 × X3 1289:1299 correlation equation: Y = - 0.625 4 + 0.020 84 × X3 + 0.001 514 × X1 × X2 - 0.000 964 4 × X2 × X3 1203:1299 The relationship between the storage factors and degree of browning (Y) could be described by following correlation equation: Y = - 0.625 4 + 0.020 84 × X3 + 0.001 514 × X1 × X2 - 0.000 964 4 × X2 × X3. 25660292 11 67 theme enzymatic 1729:1737 arg1 browning 1739:1746 enzymatic browning 1729:1746 enzymatic browning 1729:1746 The main causes of the browning were the production of 5-HMF, the activation of polyphenol oxidase, Maillard reactions and enzymatic browning. 25660292 7 68 dep activated 881:889 arg1 while 989:993 while 989:993 while 989:993 Compared with the normal Radix Ophiopogonis, cellulase and polyphenol oxidase enzymes were activated, the levels of 5-hydroxymethylfurfural (5-HMF), total sugars, and reducing sugars were increased, while the levels of polysaccharides and methylophiopogonanone A were decreased in browned Radix Ophiopogonis. 25660292 11 69 theme oxidase 1697:1703 arg1 activation 1672:1681 the activation 1668:1681 the activation of polyphenol oxidase 1668:1703 The main causes of the browning were the production of 5-HMF, the activation of polyphenol oxidase, Maillard reactions and enzymatic browning. 25660292 11 69 theme oxidase 1697:1703 arg1 production 1647:1656 the production 1643:1656 the production of 5-HMF 1643:1665 The main causes of the browning were the production of 5-HMF, the activation of polyphenol oxidase, Maillard reactions and enzymatic browning. 25660292 11 69 theme oxidase 1697:1703 arg1 reactions 1715:1723 Maillard reactions 1706:1723 Maillard reactions 1706:1723 The main causes of the browning were the production of 5-HMF, the activation of polyphenol oxidase, Maillard reactions and enzymatic browning. 25660292 11 69 theme oxidase 1697:1703 arg1 browning 1739:1746 enzymatic browning 1729:1746 enzymatic browning 1729:1746 The main causes of the browning were the production of 5-HMF, the activation of polyphenol oxidase, Maillard reactions and enzymatic browning. 25660292 11 69 theme oxidase 1697:1703 arg1 causes 1615:1620 The main causes 1606:1620 The main causes of the browning 1606:1636 The main causes of the browning were the production of 5-HMF, the activation of polyphenol oxidase, Maillard reactions and enzymatic browning. 25660292 7 70 theme Radix 1079:1083 arg1 Ophiopogonis 1085:1096 browned Radix Ophiopogonis 1071:1096 browned Radix Ophiopogonis 1071:1096 Compared with the normal Radix Ophiopogonis, cellulase and polyphenol oxidase enzymes were activated, the levels of 5-hydroxymethylfurfural (5-HMF), total sugars, and reducing sugars were increased, while the levels of polysaccharides and methylophiopogonanone A were decreased in browned Radix Ophiopogonis. 25660292 12 71 theme moisture 1843:1850 arg1 content 1852:1858 moisture content 1843:1858 moisture content 1843:1858 Browning could be effectively prevented when the air relative humidity (HR), temperature, and moisture content were under 25% RH, 12 °C and 18%, respectively. 25660292 7 72 theme total 939:943 arg1 sugars 945:950 total sugars 939:950 total sugars 939:950 Compared with the normal Radix Ophiopogonis, cellulase and polyphenol oxidase enzymes were activated, the levels of 5-hydroxymethylfurfural (5-HMF), total sugars, and reducing sugars were increased, while the levels of polysaccharides and methylophiopogonanone A were decreased in browned Radix Ophiopogonis. 25660292 8 73 theme × 1267:1267 arg1 X2 1274:1275 0.001 514 × X1 × X2 1257:1275 0.001 514 × X1 × X2 1257:1275 The relationship between the storage factors and degree of browning (Y) could be described by following correlation equation: Y = - 0.625 4 + 0.020 84 × X3 + 0.001 514 × X1 × X2 - 0.000 964 4 × X2 × X3. 25660292 2 74 theme Ophiopogonis 230:241 arg1 browning 212:219 the browning 208:219 the browning of Radix Ophiopogonis 208:241 Previously few reports investigate the browning of Radix Ophiopogonis. 25660292 7 75 theme methylophiopogonanone 1029:1049 arg1 A 1051:1051 methylophiopogonanone A 1029:1051 methylophiopogonanone A 1029:1051 Compared with the normal Radix Ophiopogonis, cellulase and polyphenol oxidase enzymes were activated, the levels of 5-hydroxymethylfurfural (5-HMF), total sugars, and reducing sugars were increased, while the levels of polysaccharides and methylophiopogonanone A were decreased in browned Radix Ophiopogonis. 25660292 10 76 theme substances 1513:1522 arg1 rupture 1457:1463 the rupture 1453:1463 the rupture of the cortex cell wall 1453:1487 Following the activation of cellulase, the rupture of the cortex cell wall and the outflow of cell substances flowed out, which caused the Radix Ophiopogonis tissue to become soft and sticky. 25660292 10 76 theme substances 1513:1522 arg1 outflow 1497:1503 the outflow 1493:1503 the outflow of cell substances 1493:1522 Following the activation of cellulase, the rupture of the cortex cell wall and the outflow of cell substances flowed out, which caused the Radix Ophiopogonis tissue to become soft and sticky. 25660292 7 77 theme sugars 945:950 arg1 levels 896:901 the levels 892:901 the levels of 5-hydroxymethylfurfural (5-HMF), total sugars, and reducing sugars 892:971 Compared with the normal Radix Ophiopogonis, cellulase and polyphenol oxidase enzymes were activated, the levels of 5-hydroxymethylfurfural (5-HMF), total sugars, and reducing sugars were increased, while the levels of polysaccharides and methylophiopogonanone A were decreased in browned Radix Ophiopogonis. 25660292 12 78 theme air 1798:1800 arg1 HR 1821:1822 HR 1821:1822 HR 1821:1822 Browning could be effectively prevented when the air relative humidity (HR), temperature, and moisture content were under 25% RH, 12 °C and 18%, respectively. 25660292 12 78 theme air 1798:1800 arg1 humidity 1811:1818 the air relative humidity 1794:1818 the air relative humidity (HR) 1794:1823 Browning could be effectively prevented when the air relative humidity (HR), temperature, and moisture content were under 25% RH, 12 °C and 18%, respectively. 25660292 2 79 theme Radix 224:228 arg1 Ophiopogonis 230:241 Radix Ophiopogonis 224:241 Radix Ophiopogonis 224:241 Previously few reports investigate the browning of Radix Ophiopogonis. 25660292 6 80 theme Ophiopogonis 763:774 arg1 wall 741:744 The cortex cell wall 725:744 The cortex cell wall of browned Radix Ophiopogonis 725:774 The cortex cell wall of browned Radix Ophiopogonis was ruptured. 25660292 9 81 theme chemical 1358:1365 arg1 composition 1367:1377 the chemical composition 1354:1377 the chemical composition of Radix Ophiopogonis 1354:1399 Accompanied with browning under storage conditions, the chemical composition of Radix Ophiopogonis was altered. 24618567 4 0 dep demonstrated 1195:1206 arg1 VI 1160:1161 VI 1160:1161 VI 1160:1161 The formation of this mineral phase is independent of the background solution but U(VI) luminescence lifetime analyses demonstrated that the U(VI) speciation in seawater samples is more intricate, i.e., different complexes were formed under natural conditions. 24618567 4 0 dep demonstrated 1195:1206 arg1 U 1158:1158 U 1158:1158 U 1158:1158 The formation of this mineral phase is independent of the background solution but U(VI) luminescence lifetime analyses demonstrated that the U(VI) speciation in seawater samples is more intricate, i.e., different complexes were formed under natural conditions. 24618567 4 0 dep demonstrated 1195:1206 arg1 i.e. 1273:1276 i.e. 1273:1276 i.e. 1273:1276 The formation of this mineral phase is independent of the background solution but U(VI) luminescence lifetime analyses demonstrated that the U(VI) speciation in seawater samples is more intricate, i.e., different complexes were formed under natural conditions. 24618567 2 1 theme electrolyte 748:758 arg1 pH 702:703 pH 702:703 pH 702:703 We showed that the U(VI)/bacterium interaction mechanism is highly dependent upon pH but also the nature of the used background electrolyte played a role. 24618567 2 1 theme electrolyte 748:758 arg1 nature 718:723 the nature 714:723 the nature of the used background electrolyte played a role 714:772 We showed that the U(VI)/bacterium interaction mechanism is highly dependent upon pH but also the nature of the used background electrolyte played a role. 24618567 4 2 theme luminescence 1164:1175 arg1 analyses 1186:1193 luminescence lifetime analyses 1164:1193 luminescence lifetime analyses 1164:1193 The formation of this mineral phase is independent of the background solution but U(VI) luminescence lifetime analyses demonstrated that the U(VI) speciation in seawater samples is more intricate, i.e., different complexes were formed under natural conditions. 24618567 5 3 from solution 1456:1463 arg1 evident 1555:1561 evident 1555:1561 evident 1555:1561 At acidic conditions, pH 2, 3 and 4.3 ([U] = 5·10(-4) M, background electrolyte = 0.1 M NaClO4), the removal of U from solution was due to biosorption to Extracellular Polysaccharides (EPS) and cell wall components as evident from TEM analysis. 24618567 5 3 from solution 1456:1463 arg1 removal 1438:1444 the removal 1434:1444 the removal of U from solution 1434:1463 At acidic conditions, pH 2, 3 and 4.3 ([U] = 5·10(-4) M, background electrolyte = 0.1 M NaClO4), the removal of U from solution was due to biosorption to Extracellular Polysaccharides (EPS) and cell wall components as evident from TEM analysis. 24618567 2 4 theme used 732:735 arg1 electrolyte 748:758 the used background electrolyte 728:758 the used background electrolyte played a role 728:772 We showed that the U(VI)/bacterium interaction mechanism is highly dependent upon pH but also the nature of the used background electrolyte played a role. 24618567 7 5 theme uranium 2059:2065 arg1 concentration 2067:2079 the uranium concentration 2055:2079 the uranium concentration 2055:2079 The differences in the complexes formed between uranium and bacteria on seawater compared to NaClO4 solution demonstrates that the actinide/microbe interactions are influenced by the three studied factors, i.e., the pH, the uranium concentration and the chemical composition of the solution. 24618567 4 6 theme solution 1145:1152 arg1 independent 1115:1125 independent 1115:1125 independent 1115:1125 The formation of this mineral phase is independent of the background solution but U(VI) luminescence lifetime analyses demonstrated that the U(VI) speciation in seawater samples is more intricate, i.e., different complexes were formed under natural conditions. 24618567 4 6 theme solution 1145:1152 arg1 formation 1080:1088 The formation 1076:1088 The formation of this mineral phase 1076:1110 The formation of this mineral phase is independent of the background solution but U(VI) luminescence lifetime analyses demonstrated that the U(VI) speciation in seawater samples is more intricate, i.e., different complexes were formed under natural conditions. 24618567 5 7 theme cell 1531:1534 arg1 components 1541:1550 cell wall components 1531:1550 cell wall components 1531:1550 At acidic conditions, pH 2, 3 and 4.3 ([U] = 5·10(-4) M, background electrolyte = 0.1 M NaClO4), the removal of U from solution was due to biosorption to Extracellular Polysaccharides (EPS) and cell wall components as evident from TEM analysis. 24618567 4 8 theme U 1217:1217 arg1 speciation 1223:1232 the U(VI) speciation 1213:1232 the U(VI) speciation in seawater samples 1213:1252 The formation of this mineral phase is independent of the background solution but U(VI) luminescence lifetime analyses demonstrated that the U(VI) speciation in seawater samples is more intricate, i.e., different complexes were formed under natural conditions. 24618567 4 8 theme U 1217:1217 arg1 intricate 1262:1270 intricate 1262:1270 intricate 1262:1270 The formation of this mineral phase is independent of the background solution but U(VI) luminescence lifetime analyses demonstrated that the U(VI) speciation in seawater samples is more intricate, i.e., different complexes were formed under natural conditions. 24618567 1 9 theme molecular 397:405 arg1 level 407:411 the molecular level 393:411 the molecular level 393:411 This was done at the molecular level using a multidisciplinary approach combining X-ray Absorption Spectroscopy (XAS), Time-Resolved Laser-Induced Fluorescence Spectroscopy (TRLFS), and High Resolution Transmission Electron Microscopy (HRTEM). 24618567 5 10 theme Extracellular 1491:1503 arg1 Polysaccharides 1505:1519 Extracellular Polysaccharides 1491:1519 Extracellular Polysaccharides (EPS) 1491:1525 At acidic conditions, pH 2, 3 and 4.3 ([U] = 5·10(-4) M, background electrolyte = 0.1 M NaClO4), the removal of U from solution was due to biosorption to Extracellular Polysaccharides (EPS) and cell wall components as evident from TEM analysis. 24618567 5 10 theme Extracellular 1491:1503 arg1 EPS 1522:1524 EPS 1522:1524 EPS 1522:1524 At acidic conditions, pH 2, 3 and 4.3 ([U] = 5·10(-4) M, background electrolyte = 0.1 M NaClO4), the removal of U from solution was due to biosorption to Extracellular Polysaccharides (EPS) and cell wall components as evident from TEM analysis. 24618567 0 11 dep is 164:165 arg1 VI 39:40 VI 39:40 VI 39:40 Biosorption and Biomineralization of U(VI) by the marine bacterium Idiomarina loihiensis MAH1: effect of background electrolyte and pH. The main goal of this study is to compare the effects of pH, uranium concentration, and background electrolyte (seawater and NaClO4 solution) on the speciation of uranium(VI) associated with the marine bacterium Idiomarina loihiensis MAH1. 24618567 5 12 theme electrolyte 1405:1415 arg1 NaClO4 1425:1430 background electrolyte = 0.1 M NaClO4 1394:1430 background electrolyte = 0.1 M NaClO4 1394:1430 At acidic conditions, pH 2, 3 and 4.3 ([U] = 5·10(-4) M, background electrolyte = 0.1 M NaClO4), the removal of U from solution was due to biosorption to Extracellular Polysaccharides (EPS) and cell wall components as evident from TEM analysis. 24618567 6 13 theme LIII-edge 1586:1594 arg1 XAS 1596:1598 The LIII-edge XAS 1582:1598 The LIII-edge XAS 1582:1598 The LIII-edge XAS and TRLFS studies showed that the biosorption process observed is dependent of pH. The bacterial cell forms a complex with U through organic phosphate groups at pH 2 and via phosphate and carboxyl groups at pH 3 and 4.3, respectively. 24618567 6 14 from 4.3 1816:1818 arg1 groups 1797:1802 phosphate and carboxyl groups 1774:1802 groups 1797:1802 The LIII-edge XAS and TRLFS studies showed that the biosorption process observed is dependent of pH. The bacterial cell forms a complex with U through organic phosphate groups at pH 2 and via phosphate and carboxyl groups at pH 3 and 4.3, respectively. 24618567 0 15 theme background 105:114 arg1 electrolyte 116:126 background electrolyte 105:126 background electrolyte 105:126 Biosorption and Biomineralization of U(VI) by the marine bacterium Idiomarina loihiensis MAH1: effect of background electrolyte and pH. The main goal of this study is to compare the effects of pH, uranium concentration, and background electrolyte (seawater and NaClO4 solution) on the speciation of uranium(VI) associated with the marine bacterium Idiomarina loihiensis MAH1. 24618567 5 16 theme TEM 1568:1570 arg1 analysis 1572:1579 TEM analysis 1568:1579 TEM analysis 1568:1579 At acidic conditions, pH 2, 3 and 4.3 ([U] = 5·10(-4) M, background electrolyte = 0.1 M NaClO4), the removal of U from solution was due to biosorption to Extracellular Polysaccharides (EPS) and cell wall components as evident from TEM analysis. 24618567 0 17 theme electrolyte 235:245 arg1 effects 182:188 the effects 178:188 the effects of pH, uranium concentration, and background electrolyte (seawater and NaClO4 solution) on the speciation of uranium(VI) associated with the marine bacterium Idiomarina loihiensis MAH1 178:373 Biosorption and Biomineralization of U(VI) by the marine bacterium Idiomarina loihiensis MAH1: effect of background electrolyte and pH. The main goal of this study is to compare the effects of pH, uranium concentration, and background electrolyte (seawater and NaClO4 solution) on the speciation of uranium(VI) associated with the marine bacterium Idiomarina loihiensis MAH1. 24618567 3 18 theme MAH1 1070:1073 arg1 surfaces 1047:1054 the cell surfaces 1038:1054 the cell surfaces of the strain MAH1 1038:1073 At neutral conditions and a U concentration ranging from 5·10(-4) to 10(-5) M (environmentally relevant concentrations), XAS analysis revealed that uranyl phosphate mineral phases, structurally resembling meta-autunite [Ca(UO2)2(PO4)2 2-6H2O] are precipitated at the cell surfaces of the strain MAH1. 24618567 2 19 theme U 639:639 arg1 mechanism 667:675 the U(VI)/bacterium interaction mechanism 635:675 the U(VI)/bacterium interaction mechanism 635:675 We showed that the U(VI)/bacterium interaction mechanism is highly dependent upon pH but also the nature of the used background electrolyte played a role. 24618567 2 19 theme U 639:639 arg1 dependent 687:695 dependent 687:695 dependent 687:695 We showed that the U(VI)/bacterium interaction mechanism is highly dependent upon pH but also the nature of the used background electrolyte played a role. 24618567 0 20 theme NaClO4 261:266 arg1 solution 268:275 NaClO4 solution 261:275 NaClO4 solution 261:275 Biosorption and Biomineralization of U(VI) by the marine bacterium Idiomarina loihiensis MAH1: effect of background electrolyte and pH. The main goal of this study is to compare the effects of pH, uranium concentration, and background electrolyte (seawater and NaClO4 solution) on the speciation of uranium(VI) associated with the marine bacterium Idiomarina loihiensis MAH1. 24618567 2 21 theme /bacterium 644:653 arg1 mechanism 667:675 the U(VI)/bacterium interaction mechanism 635:675 the U(VI)/bacterium interaction mechanism 635:675 We showed that the U(VI)/bacterium interaction mechanism is highly dependent upon pH but also the nature of the used background electrolyte played a role. 24618567 2 21 theme /bacterium 644:653 arg1 dependent 687:695 dependent 687:695 dependent 687:695 We showed that the U(VI)/bacterium interaction mechanism is highly dependent upon pH but also the nature of the used background electrolyte played a role. 24618567 7 22 from differences 1839:1849 arg1 complexes 1858:1866 the complexes 1854:1866 the complexes formed between uranium and bacteria on seawater 1854:1914 The differences in the complexes formed between uranium and bacteria on seawater compared to NaClO4 solution demonstrates that the actinide/microbe interactions are influenced by the three studied factors, i.e., the pH, the uranium concentration and the chemical composition of the solution. 24618567 7 23 theme studied 2024:2030 arg1 factors 2032:2038 the three studied factors 2014:2038 the three studied factors 2014:2038 The differences in the complexes formed between uranium and bacteria on seawater compared to NaClO4 solution demonstrates that the actinide/microbe interactions are influenced by the three studied factors, i.e., the pH, the uranium concentration and the chemical composition of the solution. 24618567 6 24 theme biosorption 1634:1644 arg1 process 1646:1652 the biosorption process 1630:1652 the biosorption process observed 1630:1661 The LIII-edge XAS and TRLFS studies showed that the biosorption process observed is dependent of pH. The bacterial cell forms a complex with U through organic phosphate groups at pH 2 and via phosphate and carboxyl groups at pH 3 and 4.3, respectively. 24618567 6 24 theme biosorption 1634:1644 arg1 dependent 1666:1674 dependent 1666:1674 dependent 1666:1674 The LIII-edge XAS and TRLFS studies showed that the biosorption process observed is dependent of pH. The bacterial cell forms a complex with U through organic phosphate groups at pH 2 and via phosphate and carboxyl groups at pH 3 and 4.3, respectively. 24618567 1 25 theme High 562:565 arg1 HRTEM 612:616 HRTEM 612:616 HRTEM 612:616 This was done at the molecular level using a multidisciplinary approach combining X-ray Absorption Spectroscopy (XAS), Time-Resolved Laser-Induced Fluorescence Spectroscopy (TRLFS), and High Resolution Transmission Electron Microscopy (HRTEM). 24618567 1 25 theme High 562:565 arg1 Microscopy 600:609 High Resolution Transmission Electron Microscopy 562:609 High Resolution Transmission Electron Microscopy (HRTEM) 562:617 This was done at the molecular level using a multidisciplinary approach combining X-ray Absorption Spectroscopy (XAS), Time-Resolved Laser-Induced Fluorescence Spectroscopy (TRLFS), and High Resolution Transmission Electron Microscopy (HRTEM). 24618567 0 26 theme marine 50:55 arg1 MAH1 89:92 the marine bacterium Idiomarina loihiensis MAH1 46:92 the marine bacterium Idiomarina loihiensis MAH1: effect of background electrolyte and pH. 46:134 Biosorption and Biomineralization of U(VI) by the marine bacterium Idiomarina loihiensis MAH1: effect of background electrolyte and pH. The main goal of this study is to compare the effects of pH, uranium concentration, and background electrolyte (seawater and NaClO4 solution) on the speciation of uranium(VI) associated with the marine bacterium Idiomarina loihiensis MAH1. 24618567 3 27 theme neutral 778:784 arg1 conditions 786:795 neutral conditions 778:795 neutral conditions 778:795 At neutral conditions and a U concentration ranging from 5·10(-4) to 10(-5) M (environmentally relevant concentrations), XAS analysis revealed that uranyl phosphate mineral phases, structurally resembling meta-autunite [Ca(UO2)2(PO4)2 2-6H2O] are precipitated at the cell surfaces of the strain MAH1. 24618567 1 28 theme Transmission 578:589 arg1 HRTEM 612:616 HRTEM 612:616 HRTEM 612:616 This was done at the molecular level using a multidisciplinary approach combining X-ray Absorption Spectroscopy (XAS), Time-Resolved Laser-Induced Fluorescence Spectroscopy (TRLFS), and High Resolution Transmission Electron Microscopy (HRTEM). 24618567 1 28 theme Transmission 578:589 arg1 Microscopy 600:609 High Resolution Transmission Electron Microscopy 562:609 High Resolution Transmission Electron Microscopy (HRTEM) 562:617 This was done at the molecular level using a multidisciplinary approach combining X-ray Absorption Spectroscopy (XAS), Time-Resolved Laser-Induced Fluorescence Spectroscopy (TRLFS), and High Resolution Transmission Electron Microscopy (HRTEM). 24618567 4 29 theme seawater 1237:1244 arg1 samples 1246:1252 seawater samples 1237:1252 seawater samples 1237:1252 The formation of this mineral phase is independent of the background solution but U(VI) luminescence lifetime analyses demonstrated that the U(VI) speciation in seawater samples is more intricate, i.e., different complexes were formed under natural conditions. 24618567 0 30 theme Idiomarina 67:76 arg1 MAH1 89:92 the marine bacterium Idiomarina loihiensis MAH1 46:92 the marine bacterium Idiomarina loihiensis MAH1: effect of background electrolyte and pH. 46:134 Biosorption and Biomineralization of U(VI) by the marine bacterium Idiomarina loihiensis MAH1: effect of background electrolyte and pH. The main goal of this study is to compare the effects of pH, uranium concentration, and background electrolyte (seawater and NaClO4 solution) on the speciation of uranium(VI) associated with the marine bacterium Idiomarina loihiensis MAH1. 24618567 3 31 theme phosphate 930:938 arg1 phases 948:953 uranyl phosphate mineral phases 923:953 uranyl phosphate mineral phases 923:953 At neutral conditions and a U concentration ranging from 5·10(-4) to 10(-5) M (environmentally relevant concentrations), XAS analysis revealed that uranyl phosphate mineral phases, structurally resembling meta-autunite [Ca(UO2)2(PO4)2 2-6H2O] are precipitated at the cell surfaces of the strain MAH1. 24618567 0 32 dep MAH1 89:92 arg1 effect 95:100 effect 95:100 the marine bacterium Idiomarina loihiensis MAH1: effect of background electrolyte and pH. 46:134 Biosorption and Biomineralization of U(VI) by the marine bacterium Idiomarina loihiensis MAH1: effect of background electrolyte and pH. The main goal of this study is to compare the effects of pH, uranium concentration, and background electrolyte (seawater and NaClO4 solution) on the speciation of uranium(VI) associated with the marine bacterium Idiomarina loihiensis MAH1. 24618567 0 33 from effects 182:188 arg1 speciation 285:294 the speciation 281:294 the speciation of uranium(VI) associated with the marine bacterium Idiomarina loihiensis MAH1 281:373 Biosorption and Biomineralization of U(VI) by the marine bacterium Idiomarina loihiensis MAH1: effect of background electrolyte and pH. The main goal of this study is to compare the effects of pH, uranium concentration, and background electrolyte (seawater and NaClO4 solution) on the speciation of uranium(VI) associated with the marine bacterium Idiomarina loihiensis MAH1. 24618567 3 34 theme meta-autunite 980:992 arg1 2-6H2O 1010:1015 meta-autunite [Ca(UO2)2(PO4)2 2-6H2O 980:1015 meta-autunite [Ca(UO2)2(PO4)2 2-6H2O 980:1015 At neutral conditions and a U concentration ranging from 5·10(-4) to 10(-5) M (environmentally relevant concentrations), XAS analysis revealed that uranyl phosphate mineral phases, structurally resembling meta-autunite [Ca(UO2)2(PO4)2 2-6H2O] are precipitated at the cell surfaces of the strain MAH1. 24618567 0 35 theme concentration 205:217 arg1 effects 182:188 the effects 178:188 the effects of pH, uranium concentration, and background electrolyte (seawater and NaClO4 solution) on the speciation of uranium(VI) associated with the marine bacterium Idiomarina loihiensis MAH1 178:373 Biosorption and Biomineralization of U(VI) by the marine bacterium Idiomarina loihiensis MAH1: effect of background electrolyte and pH. The main goal of this study is to compare the effects of pH, uranium concentration, and background electrolyte (seawater and NaClO4 solution) on the speciation of uranium(VI) associated with the marine bacterium Idiomarina loihiensis MAH1. 24618567 3 36 theme U 803:803 arg1 concentration 805:817 a U concentration 801:817 a U concentration 801:817 At neutral conditions and a U concentration ranging from 5·10(-4) to 10(-5) M (environmentally relevant concentrations), XAS analysis revealed that uranyl phosphate mineral phases, structurally resembling meta-autunite [Ca(UO2)2(PO4)2 2-6H2O] are precipitated at the cell surfaces of the strain MAH1. 24618567 5 37 theme 3 1365:1365 arg1 M 1391:1391 3 and 4.3 ([U] = 5·10(-4) M 1365:1391 M 1391:1391 At acidic conditions, pH 2, 3 and 4.3 ([U] = 5·10(-4) M, background electrolyte = 0.1 M NaClO4), the removal of U from solution was due to biosorption to Extracellular Polysaccharides (EPS) and cell wall components as evident from TEM analysis. 24618567 5 37 theme 3 1365:1365 arg1 pH 1359:1360 pH 2 1359:1362 pH 2 1359:1362 At acidic conditions, pH 2, 3 and 4.3 ([U] = 5·10(-4) M, background electrolyte = 0.1 M NaClO4), the removal of U from solution was due to biosorption to Extracellular Polysaccharides (EPS) and cell wall components as evident from TEM analysis. 24618567 5 38 from analysis 1572:1579 arg1 evident 1555:1561 evident 1555:1561 evident 1555:1561 At acidic conditions, pH 2, 3 and 4.3 ([U] = 5·10(-4) M, background electrolyte = 0.1 M NaClO4), the removal of U from solution was due to biosorption to Extracellular Polysaccharides (EPS) and cell wall components as evident from TEM analysis. 24618567 5 38 from analysis 1572:1579 arg1 removal 1438:1444 the removal 1434:1444 the removal of U from solution 1434:1463 At acidic conditions, pH 2, 3 and 4.3 ([U] = 5·10(-4) M, background electrolyte = 0.1 M NaClO4), the removal of U from solution was due to biosorption to Extracellular Polysaccharides (EPS) and cell wall components as evident from TEM analysis. 24618567 6 39 dep cell 1697:1700 arg1 forms 1702:1706 forms 1702:1706 forms a complex with U through organic phosphate groups at pH 2 and via phosphate and carboxyl groups at pH 3 and 4.3, respectively 1702:1832 The LIII-edge XAS and TRLFS studies showed that the biosorption process observed is dependent of pH. The bacterial cell forms a complex with U through organic phosphate groups at pH 2 and via phosphate and carboxyl groups at pH 3 and 4.3, respectively. 24618567 6 39 dep cell 1697:1700 arg1 pH. 1679:1681 pH. The bacterial cell forms a complex with U through organic phosphate groups at pH 2 and via phosphate and carboxyl groups at pH 3 and 4.3, respectively 1679:1832 pH. The bacterial cell forms a complex with U through organic phosphate groups at pH 2 and via phosphate and carboxyl groups at pH 3 and 4.3, respectively 1679:1832 The LIII-edge XAS and TRLFS studies showed that the biosorption process observed is dependent of pH. The bacterial cell forms a complex with U through organic phosphate groups at pH 2 and via phosphate and carboxyl groups at pH 3 and 4.3, respectively. 24618567 5 40 theme acidic 1340:1345 arg1 conditions 1347:1356 acidic conditions 1340:1356 acidic conditions, pH 2, 3 and 4.3 ([U] = 5·10(-4) M, background electrolyte = 0.1 M NaClO4) 1340:1431 At acidic conditions, pH 2, 3 and 4.3 ([U] = 5·10(-4) M, background electrolyte = 0.1 M NaClO4), the removal of U from solution was due to biosorption to Extracellular Polysaccharides (EPS) and cell wall components as evident from TEM analysis. 24618567 6 41 theme bacterial 1687:1695 arg1 cell 1697:1700 The bacterial cell 1683:1700 pH. The bacterial cell forms a complex with U through organic phosphate groups at pH 2 and via phosphate and carboxyl groups at pH 3 and 4.3, respectively 1679:1832 The LIII-edge XAS and TRLFS studies showed that the biosorption process observed is dependent of pH. The bacterial cell forms a complex with U through organic phosphate groups at pH 2 and via phosphate and carboxyl groups at pH 3 and 4.3, respectively. 24618567 1 42 theme Laser-Induced 509:521 arg1 TRLFS 550:554 TRLFS 550:554 TRLFS 550:554 This was done at the molecular level using a multidisciplinary approach combining X-ray Absorption Spectroscopy (XAS), Time-Resolved Laser-Induced Fluorescence Spectroscopy (TRLFS), and High Resolution Transmission Electron Microscopy (HRTEM). 24618567 1 42 theme Laser-Induced 509:521 arg1 Spectroscopy 536:547 Time-Resolved Laser-Induced Fluorescence Spectroscopy 495:547 Time-Resolved Laser-Induced Fluorescence Spectroscopy (TRLFS) 495:555 This was done at the molecular level using a multidisciplinary approach combining X-ray Absorption Spectroscopy (XAS), Time-Resolved Laser-Induced Fluorescence Spectroscopy (TRLFS), and High Resolution Transmission Electron Microscopy (HRTEM). 24618567 5 43 theme = 1417:1417 arg1 NaClO4 1425:1430 background electrolyte = 0.1 M NaClO4 1394:1430 background electrolyte = 0.1 M NaClO4 1394:1430 At acidic conditions, pH 2, 3 and 4.3 ([U] = 5·10(-4) M, background electrolyte = 0.1 M NaClO4), the removal of U from solution was due to biosorption to Extracellular Polysaccharides (EPS) and cell wall components as evident from TEM analysis. 24618567 4 44 theme different 1279:1287 arg1 complexes 1289:1297 different complexes 1279:1297 different complexes 1279:1297 The formation of this mineral phase is independent of the background solution but U(VI) luminescence lifetime analyses demonstrated that the U(VI) speciation in seawater samples is more intricate, i.e., different complexes were formed under natural conditions. 24618567 5 45 theme M 1423:1423 arg1 NaClO4 1425:1430 background electrolyte = 0.1 M NaClO4 1394:1430 background electrolyte = 0.1 M NaClO4 1394:1430 At acidic conditions, pH 2, 3 and 4.3 ([U] = 5·10(-4) M, background electrolyte = 0.1 M NaClO4), the removal of U from solution was due to biosorption to Extracellular Polysaccharides (EPS) and cell wall components as evident from TEM analysis. 24618567 0 46 theme U 37:37 arg1 Biomineralization 16:32 Biomineralization 16:32 Biomineralization 16:32 Biosorption and Biomineralization of U(VI) by the marine bacterium Idiomarina loihiensis MAH1: effect of background electrolyte and pH. The main goal of this study is to compare the effects of pH, uranium concentration, and background electrolyte (seawater and NaClO4 solution) on the speciation of uranium(VI) associated with the marine bacterium Idiomarina loihiensis MAH1. 24618567 0 46 theme U 37:37 arg1 Biosorption 0:10 Biosorption 0:10 Biosorption 0:10 Biosorption and Biomineralization of U(VI) by the marine bacterium Idiomarina loihiensis MAH1: effect of background electrolyte and pH. The main goal of this study is to compare the effects of pH, uranium concentration, and background electrolyte (seawater and NaClO4 solution) on the speciation of uranium(VI) associated with the marine bacterium Idiomarina loihiensis MAH1. 24618567 4 47 dep speciation 1223:1232 arg1 VI 1219:1220 VI 1219:1220 VI 1219:1220 The formation of this mineral phase is independent of the background solution but U(VI) luminescence lifetime analyses demonstrated that the U(VI) speciation in seawater samples is more intricate, i.e., different complexes were formed under natural conditions. 24618567 0 48 dep electrolyte 235:245 arg1 seawater 248:255 seawater 248:255 seawater 248:255 Biosorption and Biomineralization of U(VI) by the marine bacterium Idiomarina loihiensis MAH1: effect of background electrolyte and pH. The main goal of this study is to compare the effects of pH, uranium concentration, and background electrolyte (seawater and NaClO4 solution) on the speciation of uranium(VI) associated with the marine bacterium Idiomarina loihiensis MAH1. 24618567 0 48 dep electrolyte 235:245 arg1 solution 268:275 NaClO4 solution 261:275 NaClO4 solution 261:275 Biosorption and Biomineralization of U(VI) by the marine bacterium Idiomarina loihiensis MAH1: effect of background electrolyte and pH. The main goal of this study is to compare the effects of pH, uranium concentration, and background electrolyte (seawater and NaClO4 solution) on the speciation of uranium(VI) associated with the marine bacterium Idiomarina loihiensis MAH1. 24618567 6 49 from pH 1761:1762 arg1 groups 1751:1756 organic phosphate groups 1733:1756 organic phosphate groups at pH 2 1733:1764 The LIII-edge XAS and TRLFS studies showed that the biosorption process observed is dependent of pH. The bacterial cell forms a complex with U through organic phosphate groups at pH 2 and via phosphate and carboxyl groups at pH 3 and 4.3, respectively. 24618567 5 50 theme 4.3 1371:1373 arg1 M 1391:1391 3 and 4.3 ([U] = 5·10(-4) M 1365:1391 M 1391:1391 At acidic conditions, pH 2, 3 and 4.3 ([U] = 5·10(-4) M, background electrolyte = 0.1 M NaClO4), the removal of U from solution was due to biosorption to Extracellular Polysaccharides (EPS) and cell wall components as evident from TEM analysis. 24618567 5 50 theme 4.3 1371:1373 arg1 pH 1359:1360 pH 2 1359:1362 pH 2 1359:1362 At acidic conditions, pH 2, 3 and 4.3 ([U] = 5·10(-4) M, background electrolyte = 0.1 M NaClO4), the removal of U from solution was due to biosorption to Extracellular Polysaccharides (EPS) and cell wall components as evident from TEM analysis. 24618567 4 51 theme mineral 1098:1104 arg1 phase 1106:1110 this mineral phase 1093:1110 this mineral phase 1093:1110 The formation of this mineral phase is independent of the background solution but U(VI) luminescence lifetime analyses demonstrated that the U(VI) speciation in seawater samples is more intricate, i.e., different complexes were formed under natural conditions. 24618567 6 52 theme organic 1733:1739 arg1 groups 1751:1756 organic phosphate groups 1733:1756 organic phosphate groups at pH 2 1733:1764 The LIII-edge XAS and TRLFS studies showed that the biosorption process observed is dependent of pH. The bacterial cell forms a complex with U through organic phosphate groups at pH 2 and via phosphate and carboxyl groups at pH 3 and 4.3, respectively. 24618567 1 53 theme X-ray 458:462 arg1 XAS 489:491 XAS 489:491 XAS 489:491 This was done at the molecular level using a multidisciplinary approach combining X-ray Absorption Spectroscopy (XAS), Time-Resolved Laser-Induced Fluorescence Spectroscopy (TRLFS), and High Resolution Transmission Electron Microscopy (HRTEM). 24618567 1 53 theme X-ray 458:462 arg1 Spectroscopy 475:486 X-ray Absorption Spectroscopy 458:486 X-ray Absorption Spectroscopy (XAS) 458:492 This was done at the molecular level using a multidisciplinary approach combining X-ray Absorption Spectroscopy (XAS), Time-Resolved Laser-Induced Fluorescence Spectroscopy (TRLFS), and High Resolution Transmission Electron Microscopy (HRTEM). 24618567 5 54 dep pH 1359:1360 arg1 NaClO4 1425:1430 background electrolyte = 0.1 M NaClO4 1394:1430 background electrolyte = 0.1 M NaClO4 1394:1430 At acidic conditions, pH 2, 3 and 4.3 ([U] = 5·10(-4) M, background electrolyte = 0.1 M NaClO4), the removal of U from solution was due to biosorption to Extracellular Polysaccharides (EPS) and cell wall components as evident from TEM analysis. 24618567 0 55 theme bacterium 338:346 arg1 MAH1 370:373 the marine bacterium Idiomarina loihiensis MAH1 327:373 the marine bacterium Idiomarina loihiensis MAH1 327:373 Biosorption and Biomineralization of U(VI) by the marine bacterium Idiomarina loihiensis MAH1: effect of background electrolyte and pH. The main goal of this study is to compare the effects of pH, uranium concentration, and background electrolyte (seawater and NaClO4 solution) on the speciation of uranium(VI) associated with the marine bacterium Idiomarina loihiensis MAH1. 24618567 5 56 dep conditions 1347:1356 arg1 M 1391:1391 3 and 4.3 ([U] = 5·10(-4) M 1365:1391 M 1391:1391 At acidic conditions, pH 2, 3 and 4.3 ([U] = 5·10(-4) M, background electrolyte = 0.1 M NaClO4), the removal of U from solution was due to biosorption to Extracellular Polysaccharides (EPS) and cell wall components as evident from TEM analysis. 24618567 5 56 dep conditions 1347:1356 arg1 pH 1359:1360 pH 2 1359:1362 pH 2 1359:1362 At acidic conditions, pH 2, 3 and 4.3 ([U] = 5·10(-4) M, background electrolyte = 0.1 M NaClO4), the removal of U from solution was due to biosorption to Extracellular Polysaccharides (EPS) and cell wall components as evident from TEM analysis. 24618567 2 57 theme background 737:746 arg1 electrolyte 748:758 the used background electrolyte 728:758 the used background electrolyte played a role 728:772 We showed that the U(VI)/bacterium interaction mechanism is highly dependent upon pH but also the nature of the used background electrolyte played a role. 24618567 0 58 theme study 158:162 arg1 goal 145:148 The main goal 136:148 The main goal of this study 136:162 Biosorption and Biomineralization of U(VI) by the marine bacterium Idiomarina loihiensis MAH1: effect of background electrolyte and pH. The main goal of this study is to compare the effects of pH, uranium concentration, and background electrolyte (seawater and NaClO4 solution) on the speciation of uranium(VI) associated with the marine bacterium Idiomarina loihiensis MAH1. 24618567 0 59 theme loihiensis 359:368 arg1 MAH1 370:373 the marine bacterium Idiomarina loihiensis MAH1 327:373 the marine bacterium Idiomarina loihiensis MAH1 327:373 Biosorption and Biomineralization of U(VI) by the marine bacterium Idiomarina loihiensis MAH1: effect of background electrolyte and pH. The main goal of this study is to compare the effects of pH, uranium concentration, and background electrolyte (seawater and NaClO4 solution) on the speciation of uranium(VI) associated with the marine bacterium Idiomarina loihiensis MAH1. 24618567 3 60 theme cell 1042:1045 arg1 surfaces 1047:1054 the cell surfaces 1038:1054 the cell surfaces of the strain MAH1 1038:1073 At neutral conditions and a U concentration ranging from 5·10(-4) to 10(-5) M (environmentally relevant concentrations), XAS analysis revealed that uranyl phosphate mineral phases, structurally resembling meta-autunite [Ca(UO2)2(PO4)2 2-6H2O] are precipitated at the cell surfaces of the strain MAH1. 24618567 3 61 from surfaces 1047:1054 arg1 precipitated 1022:1033 precipitated 1022:1033 precipitated 1022:1033 At neutral conditions and a U concentration ranging from 5·10(-4) to 10(-5) M (environmentally relevant concentrations), XAS analysis revealed that uranyl phosphate mineral phases, structurally resembling meta-autunite [Ca(UO2)2(PO4)2 2-6H2O] are precipitated at the cell surfaces of the strain MAH1. 24618567 3 62 theme relevant 870:877 arg1 concentrations 879:892 environmentally relevant concentrations 854:892 10(-5) M (environmentally relevant concentrations) 844:893 At neutral conditions and a U concentration ranging from 5·10(-4) to 10(-5) M (environmentally relevant concentrations), XAS analysis revealed that uranyl phosphate mineral phases, structurally resembling meta-autunite [Ca(UO2)2(PO4)2 2-6H2O] are precipitated at the cell surfaces of the strain MAH1. 24618567 7 63 theme NaClO4 1928:1933 arg1 solution 1935:1942 NaClO4 solution 1928:1942 NaClO4 solution 1928:1942 The differences in the complexes formed between uranium and bacteria on seawater compared to NaClO4 solution demonstrates that the actinide/microbe interactions are influenced by the three studied factors, i.e., the pH, the uranium concentration and the chemical composition of the solution. 24618567 4 64 from speciation 1223:1232 arg1 samples 1246:1252 seawater samples 1237:1252 seawater samples 1237:1252 The formation of this mineral phase is independent of the background solution but U(VI) luminescence lifetime analyses demonstrated that the U(VI) speciation in seawater samples is more intricate, i.e., different complexes were formed under natural conditions. 24618567 4 65 theme background 1134:1143 arg1 solution 1145:1152 the background solution 1130:1152 the background solution 1130:1152 The formation of this mineral phase is independent of the background solution but U(VI) luminescence lifetime analyses demonstrated that the U(VI) speciation in seawater samples is more intricate, i.e., different complexes were formed under natural conditions. 24618567 1 66 theme Electron 591:598 arg1 HRTEM 612:616 HRTEM 612:616 HRTEM 612:616 This was done at the molecular level using a multidisciplinary approach combining X-ray Absorption Spectroscopy (XAS), Time-Resolved Laser-Induced Fluorescence Spectroscopy (TRLFS), and High Resolution Transmission Electron Microscopy (HRTEM). 24618567 1 66 theme Electron 591:598 arg1 Microscopy 600:609 High Resolution Transmission Electron Microscopy 562:609 High Resolution Transmission Electron Microscopy (HRTEM) 562:617 This was done at the molecular level using a multidisciplinary approach combining X-ray Absorption Spectroscopy (XAS), Time-Resolved Laser-Induced Fluorescence Spectroscopy (TRLFS), and High Resolution Transmission Electron Microscopy (HRTEM). 24618567 3 67 theme strain 1063:1068 arg1 MAH1 1070:1073 the strain MAH1 1059:1073 the strain MAH1 1059:1073 At neutral conditions and a U concentration ranging from 5·10(-4) to 10(-5) M (environmentally relevant concentrations), XAS analysis revealed that uranyl phosphate mineral phases, structurally resembling meta-autunite [Ca(UO2)2(PO4)2 2-6H2O] are precipitated at the cell surfaces of the strain MAH1. 24618567 3 68 theme XAS 896:898 arg1 analysis 900:907 XAS analysis 896:907 XAS analysis 896:907 At neutral conditions and a U concentration ranging from 5·10(-4) to 10(-5) M (environmentally relevant concentrations), XAS analysis revealed that uranyl phosphate mineral phases, structurally resembling meta-autunite [Ca(UO2)2(PO4)2 2-6H2O] are precipitated at the cell surfaces of the strain MAH1. 24618567 6 69 theme TRLFS 1604:1608 arg1 studies 1610:1616 The LIII-edge XAS and TRLFS studies 1582:1616 The LIII-edge XAS and TRLFS studies 1582:1616 The LIII-edge XAS and TRLFS studies showed that the biosorption process observed is dependent of pH. The bacterial cell forms a complex with U through organic phosphate groups at pH 2 and via phosphate and carboxyl groups at pH 3 and 4.3, respectively. 24618567 5 70 theme background 1394:1403 arg1 NaClO4 1425:1430 background electrolyte = 0.1 M NaClO4 1394:1430 background electrolyte = 0.1 M NaClO4 1394:1430 At acidic conditions, pH 2, 3 and 4.3 ([U] = 5·10(-4) M, background electrolyte = 0.1 M NaClO4), the removal of U from solution was due to biosorption to Extracellular Polysaccharides (EPS) and cell wall components as evident from TEM analysis. 24618567 0 71 theme uranium 299:305 arg1 speciation 285:294 the speciation 281:294 the speciation of uranium(VI) associated with the marine bacterium Idiomarina loihiensis MAH1 281:373 Biosorption and Biomineralization of U(VI) by the marine bacterium Idiomarina loihiensis MAH1: effect of background electrolyte and pH. The main goal of this study is to compare the effects of pH, uranium concentration, and background electrolyte (seawater and NaClO4 solution) on the speciation of uranium(VI) associated with the marine bacterium Idiomarina loihiensis MAH1. 24618567 6 72 theme XAS 1596:1598 arg1 studies 1610:1616 The LIII-edge XAS and TRLFS studies 1582:1616 The LIII-edge XAS and TRLFS studies 1582:1616 The LIII-edge XAS and TRLFS studies showed that the biosorption process observed is dependent of pH. The bacterial cell forms a complex with U through organic phosphate groups at pH 2 and via phosphate and carboxyl groups at pH 3 and 4.3, respectively. 24618567 0 73 theme electrolyte 116:126 arg1 MAH1 89:92 the marine bacterium Idiomarina loihiensis MAH1 46:92 the marine bacterium Idiomarina loihiensis MAH1: effect of background electrolyte and pH. 46:134 Biosorption and Biomineralization of U(VI) by the marine bacterium Idiomarina loihiensis MAH1: effect of background electrolyte and pH. The main goal of this study is to compare the effects of pH, uranium concentration, and background electrolyte (seawater and NaClO4 solution) on the speciation of uranium(VI) associated with the marine bacterium Idiomarina loihiensis MAH1. 24618567 4 74 theme lifetime 1177:1184 arg1 analyses 1186:1193 luminescence lifetime analyses 1164:1193 luminescence lifetime analyses 1164:1193 The formation of this mineral phase is independent of the background solution but U(VI) luminescence lifetime analyses demonstrated that the U(VI) speciation in seawater samples is more intricate, i.e., different complexes were formed under natural conditions. 24618567 0 75 theme pH. 132:134 arg1 MAH1 89:92 the marine bacterium Idiomarina loihiensis MAH1 46:92 the marine bacterium Idiomarina loihiensis MAH1: effect of background electrolyte and pH. 46:134 Biosorption and Biomineralization of U(VI) by the marine bacterium Idiomarina loihiensis MAH1: effect of background electrolyte and pH. The main goal of this study is to compare the effects of pH, uranium concentration, and background electrolyte (seawater and NaClO4 solution) on the speciation of uranium(VI) associated with the marine bacterium Idiomarina loihiensis MAH1. 24618567 0 76 theme background 224:233 arg1 electrolyte 235:245 background electrolyte 224:245 background electrolyte (seawater and NaClO4 solution) 224:276 Biosorption and Biomineralization of U(VI) by the marine bacterium Idiomarina loihiensis MAH1: effect of background electrolyte and pH. The main goal of this study is to compare the effects of pH, uranium concentration, and background electrolyte (seawater and NaClO4 solution) on the speciation of uranium(VI) associated with the marine bacterium Idiomarina loihiensis MAH1. 24618567 0 77 theme main 140:143 arg1 goal 145:148 The main goal 136:148 The main goal of this study 136:162 Biosorption and Biomineralization of U(VI) by the marine bacterium Idiomarina loihiensis MAH1: effect of background electrolyte and pH. The main goal of this study is to compare the effects of pH, uranium concentration, and background electrolyte (seawater and NaClO4 solution) on the speciation of uranium(VI) associated with the marine bacterium Idiomarina loihiensis MAH1. 24618567 5 78 theme wall 1536:1539 arg1 components 1541:1550 cell wall components 1531:1550 cell wall components 1531:1550 At acidic conditions, pH 2, 3 and 4.3 ([U] = 5·10(-4) M, background electrolyte = 0.1 M NaClO4), the removal of U from solution was due to biosorption to Extracellular Polysaccharides (EPS) and cell wall components as evident from TEM analysis. 24618567 2 79 theme interaction 655:665 arg1 mechanism 667:675 the U(VI)/bacterium interaction mechanism 635:675 the U(VI)/bacterium interaction mechanism 635:675 We showed that the U(VI)/bacterium interaction mechanism is highly dependent upon pH but also the nature of the used background electrolyte played a role. 24618567 2 79 theme interaction 655:665 arg1 dependent 687:695 dependent 687:695 dependent 687:695 We showed that the U(VI)/bacterium interaction mechanism is highly dependent upon pH but also the nature of the used background electrolyte played a role. 24618567 3 80 dep M 851:851 arg1 concentrations 879:892 environmentally relevant concentrations 854:892 10(-5) M (environmentally relevant concentrations) 844:893 At neutral conditions and a U concentration ranging from 5·10(-4) to 10(-5) M (environmentally relevant concentrations), XAS analysis revealed that uranyl phosphate mineral phases, structurally resembling meta-autunite [Ca(UO2)2(PO4)2 2-6H2O] are precipitated at the cell surfaces of the strain MAH1. 24618567 7 81 dep pH 2051:2052 arg1 i.e. 2041:2044 i.e. 2041:2044 i.e. 2041:2044 The differences in the complexes formed between uranium and bacteria on seawater compared to NaClO4 solution demonstrates that the actinide/microbe interactions are influenced by the three studied factors, i.e., the pH, the uranium concentration and the chemical composition of the solution. 24618567 0 82 dep associated 311:320 arg1 VI 307:308 VI 307:308 VI 307:308 Biosorption and Biomineralization of U(VI) by the marine bacterium Idiomarina loihiensis MAH1: effect of background electrolyte and pH. The main goal of this study is to compare the effects of pH, uranium concentration, and background electrolyte (seawater and NaClO4 solution) on the speciation of uranium(VI) associated with the marine bacterium Idiomarina loihiensis MAH1. 24618567 6 83 from pH 1807:1808 arg1 groups 1797:1802 phosphate and carboxyl groups 1774:1802 groups 1797:1802 The LIII-edge XAS and TRLFS studies showed that the biosorption process observed is dependent of pH. The bacterial cell forms a complex with U through organic phosphate groups at pH 2 and via phosphate and carboxyl groups at pH 3 and 4.3, respectively. 24618567 0 84 theme bacterium 57:65 arg1 MAH1 89:92 the marine bacterium Idiomarina loihiensis MAH1 46:92 the marine bacterium Idiomarina loihiensis MAH1: effect of background electrolyte and pH. 46:134 Biosorption and Biomineralization of U(VI) by the marine bacterium Idiomarina loihiensis MAH1: effect of background electrolyte and pH. The main goal of this study is to compare the effects of pH, uranium concentration, and background electrolyte (seawater and NaClO4 solution) on the speciation of uranium(VI) associated with the marine bacterium Idiomarina loihiensis MAH1. 24618567 3 85 theme mineral 940:946 arg1 phases 948:953 uranyl phosphate mineral phases 923:953 uranyl phosphate mineral phases 923:953 At neutral conditions and a U concentration ranging from 5·10(-4) to 10(-5) M (environmentally relevant concentrations), XAS analysis revealed that uranyl phosphate mineral phases, structurally resembling meta-autunite [Ca(UO2)2(PO4)2 2-6H2O] are precipitated at the cell surfaces of the strain MAH1. 24618567 1 86 theme Resolution 567:576 arg1 HRTEM 612:616 HRTEM 612:616 HRTEM 612:616 This was done at the molecular level using a multidisciplinary approach combining X-ray Absorption Spectroscopy (XAS), Time-Resolved Laser-Induced Fluorescence Spectroscopy (TRLFS), and High Resolution Transmission Electron Microscopy (HRTEM). 24618567 1 86 theme Resolution 567:576 arg1 Microscopy 600:609 High Resolution Transmission Electron Microscopy 562:609 High Resolution Transmission Electron Microscopy (HRTEM) 562:617 This was done at the molecular level using a multidisciplinary approach combining X-ray Absorption Spectroscopy (XAS), Time-Resolved Laser-Induced Fluorescence Spectroscopy (TRLFS), and High Resolution Transmission Electron Microscopy (HRTEM). 24618567 0 87 theme loihiensis 78:87 arg1 MAH1 89:92 the marine bacterium Idiomarina loihiensis MAH1 46:92 the marine bacterium Idiomarina loihiensis MAH1: effect of background electrolyte and pH. 46:134 Biosorption and Biomineralization of U(VI) by the marine bacterium Idiomarina loihiensis MAH1: effect of background electrolyte and pH. The main goal of this study is to compare the effects of pH, uranium concentration, and background electrolyte (seawater and NaClO4 solution) on the speciation of uranium(VI) associated with the marine bacterium Idiomarina loihiensis MAH1. 24618567 0 88 dep uranium 299:305 arg1 associated 311:320 associated 311:320 (VI) associated with the marine bacterium Idiomarina loihiensis MAH1 306:373 Biosorption and Biomineralization of U(VI) by the marine bacterium Idiomarina loihiensis MAH1: effect of background electrolyte and pH. The main goal of this study is to compare the effects of pH, uranium concentration, and background electrolyte (seawater and NaClO4 solution) on the speciation of uranium(VI) associated with the marine bacterium Idiomarina loihiensis MAH1. 24618567 3 89 theme uranyl 923:928 arg1 phosphate 930:938 uranyl phosphate 923:938 uranyl phosphate mineral phases 923:953 At neutral conditions and a U concentration ranging from 5·10(-4) to 10(-5) M (environmentally relevant concentrations), XAS analysis revealed that uranyl phosphate mineral phases, structurally resembling meta-autunite [Ca(UO2)2(PO4)2 2-6H2O] are precipitated at the cell surfaces of the strain MAH1. 24618567 6 90 theme carboxyl 1788:1795 arg1 groups 1797:1802 phosphate and carboxyl groups 1774:1802 groups 1797:1802 The LIII-edge XAS and TRLFS studies showed that the biosorption process observed is dependent of pH. The bacterial cell forms a complex with U through organic phosphate groups at pH 2 and via phosphate and carboxyl groups at pH 3 and 4.3, respectively. 24618567 0 91 theme pH 193:194 arg1 effects 182:188 the effects 178:188 the effects of pH, uranium concentration, and background electrolyte (seawater and NaClO4 solution) on the speciation of uranium(VI) associated with the marine bacterium Idiomarina loihiensis MAH1 178:373 Biosorption and Biomineralization of U(VI) by the marine bacterium Idiomarina loihiensis MAH1: effect of background electrolyte and pH. The main goal of this study is to compare the effects of pH, uranium concentration, and background electrolyte (seawater and NaClO4 solution) on the speciation of uranium(VI) associated with the marine bacterium Idiomarina loihiensis MAH1. 24618567 5 92 from conditions 1347:1356 arg1 evident 1555:1561 evident 1555:1561 evident 1555:1561 At acidic conditions, pH 2, 3 and 4.3 ([U] = 5·10(-4) M, background electrolyte = 0.1 M NaClO4), the removal of U from solution was due to biosorption to Extracellular Polysaccharides (EPS) and cell wall components as evident from TEM analysis. 24618567 5 92 from conditions 1347:1356 arg1 removal 1438:1444 the removal 1434:1444 the removal of U from solution 1434:1463 At acidic conditions, pH 2, 3 and 4.3 ([U] = 5·10(-4) M, background electrolyte = 0.1 M NaClO4), the removal of U from solution was due to biosorption to Extracellular Polysaccharides (EPS) and cell wall components as evident from TEM analysis. 24618567 7 93 theme actinide/microbe 1966:1981 arg1 interactions 1983:1994 the actinide/microbe interactions 1962:1994 the actinide/microbe interactions 1962:1994 The differences in the complexes formed between uranium and bacteria on seawater compared to NaClO4 solution demonstrates that the actinide/microbe interactions are influenced by the three studied factors, i.e., the pH, the uranium concentration and the chemical composition of the solution. 24618567 6 94 theme phosphate 1774:1782 arg1 groups 1797:1802 phosphate and carboxyl groups 1774:1802 groups 1797:1802 The LIII-edge XAS and TRLFS studies showed that the biosorption process observed is dependent of pH. The bacterial cell forms a complex with U through organic phosphate groups at pH 2 and via phosphate and carboxyl groups at pH 3 and 4.3, respectively. 24618567 0 95 theme uranium 197:203 arg1 concentration 205:217 uranium concentration 197:217 uranium concentration 197:217 Biosorption and Biomineralization of U(VI) by the marine bacterium Idiomarina loihiensis MAH1: effect of background electrolyte and pH. The main goal of this study is to compare the effects of pH, uranium concentration, and background electrolyte (seawater and NaClO4 solution) on the speciation of uranium(VI) associated with the marine bacterium Idiomarina loihiensis MAH1. 24618567 6 96 with complex 1710:1716 arg1 U 1723:1723 U 1723:1723 U 1723:1723 The LIII-edge XAS and TRLFS studies showed that the biosorption process observed is dependent of pH. The bacterial cell forms a complex with U through organic phosphate groups at pH 2 and via phosphate and carboxyl groups at pH 3 and 4.3, respectively. 24618567 6 97 theme cell 1697:1700 arg1 process 1646:1652 the biosorption process 1630:1652 the biosorption process observed 1630:1661 The LIII-edge XAS and TRLFS studies showed that the biosorption process observed is dependent of pH. The bacterial cell forms a complex with U through organic phosphate groups at pH 2 and via phosphate and carboxyl groups at pH 3 and 4.3, respectively. 24618567 6 97 theme cell 1697:1700 arg1 dependent 1666:1674 dependent 1666:1674 dependent 1666:1674 The LIII-edge XAS and TRLFS studies showed that the biosorption process observed is dependent of pH. The bacterial cell forms a complex with U through organic phosphate groups at pH 2 and via phosphate and carboxyl groups at pH 3 and 4.3, respectively. 24618567 1 98 theme Time-Resolved 495:507 arg1 TRLFS 550:554 TRLFS 550:554 TRLFS 550:554 This was done at the molecular level using a multidisciplinary approach combining X-ray Absorption Spectroscopy (XAS), Time-Resolved Laser-Induced Fluorescence Spectroscopy (TRLFS), and High Resolution Transmission Electron Microscopy (HRTEM). 24618567 1 98 theme Time-Resolved 495:507 arg1 Spectroscopy 536:547 Time-Resolved Laser-Induced Fluorescence Spectroscopy 495:547 Time-Resolved Laser-Induced Fluorescence Spectroscopy (TRLFS) 495:555 This was done at the molecular level using a multidisciplinary approach combining X-ray Absorption Spectroscopy (XAS), Time-Resolved Laser-Induced Fluorescence Spectroscopy (TRLFS), and High Resolution Transmission Electron Microscopy (HRTEM). 24618567 3 99 theme UO2 998:1000 arg1 2-6H2O 1010:1015 meta-autunite [Ca(UO2)2(PO4)2 2-6H2O 980:1015 meta-autunite [Ca(UO2)2(PO4)2 2-6H2O 980:1015 At neutral conditions and a U concentration ranging from 5·10(-4) to 10(-5) M (environmentally relevant concentrations), XAS analysis revealed that uranyl phosphate mineral phases, structurally resembling meta-autunite [Ca(UO2)2(PO4)2 2-6H2O] are precipitated at the cell surfaces of the strain MAH1. 24618567 1 100 theme Fluorescence 523:534 arg1 TRLFS 550:554 TRLFS 550:554 TRLFS 550:554 This was done at the molecular level using a multidisciplinary approach combining X-ray Absorption Spectroscopy (XAS), Time-Resolved Laser-Induced Fluorescence Spectroscopy (TRLFS), and High Resolution Transmission Electron Microscopy (HRTEM). 24618567 1 100 theme Fluorescence 523:534 arg1 Spectroscopy 536:547 Time-Resolved Laser-Induced Fluorescence Spectroscopy 495:547 Time-Resolved Laser-Induced Fluorescence Spectroscopy (TRLFS) 495:555 This was done at the molecular level using a multidisciplinary approach combining X-ray Absorption Spectroscopy (XAS), Time-Resolved Laser-Induced Fluorescence Spectroscopy (TRLFS), and High Resolution Transmission Electron Microscopy (HRTEM). 24618567 3 101 theme [Ca 994:996 arg1 2-6H2O 1010:1015 meta-autunite [Ca(UO2)2(PO4)2 2-6H2O 980:1015 meta-autunite [Ca(UO2)2(PO4)2 2-6H2O 980:1015 At neutral conditions and a U concentration ranging from 5·10(-4) to 10(-5) M (environmentally relevant concentrations), XAS analysis revealed that uranyl phosphate mineral phases, structurally resembling meta-autunite [Ca(UO2)2(PO4)2 2-6H2O] are precipitated at the cell surfaces of the strain MAH1. 24618567 7 102 theme solution 2117:2124 arg1 pH 2051:2052 the pH 2047:2052 the pH 2047:2052 The differences in the complexes formed between uranium and bacteria on seawater compared to NaClO4 solution demonstrates that the actinide/microbe interactions are influenced by the three studied factors, i.e., the pH, the uranium concentration and the chemical composition of the solution. 24618567 7 102 theme solution 2117:2124 arg1 concentration 2067:2079 the uranium concentration 2055:2079 the uranium concentration 2055:2079 The differences in the complexes formed between uranium and bacteria on seawater compared to NaClO4 solution demonstrates that the actinide/microbe interactions are influenced by the three studied factors, i.e., the pH, the uranium concentration and the chemical composition of the solution. 24618567 7 102 theme solution 2117:2124 arg1 composition 2098:2108 the chemical composition 2085:2108 the chemical composition of the solution 2085:2124 The differences in the complexes formed between uranium and bacteria on seawater compared to NaClO4 solution demonstrates that the actinide/microbe interactions are influenced by the three studied factors, i.e., the pH, the uranium concentration and the chemical composition of the solution. 24618567 1 103 theme multidisciplinary 421:437 arg1 approach 439:446 a multidisciplinary approach 419:446 a multidisciplinary approach combining X-ray Absorption Spectroscopy (XAS), Time-Resolved Laser-Induced Fluorescence Spectroscopy (TRLFS), and High Resolution Transmission Electron Microscopy (HRTEM) 419:617 This was done at the molecular level using a multidisciplinary approach combining X-ray Absorption Spectroscopy (XAS), Time-Resolved Laser-Induced Fluorescence Spectroscopy (TRLFS), and High Resolution Transmission Electron Microscopy (HRTEM). 24618567 4 104 theme phase 1106:1110 arg1 independent 1115:1125 independent 1115:1125 independent 1115:1125 The formation of this mineral phase is independent of the background solution but U(VI) luminescence lifetime analyses demonstrated that the U(VI) speciation in seawater samples is more intricate, i.e., different complexes were formed under natural conditions. 24618567 4 104 theme phase 1106:1110 arg1 formation 1080:1088 The formation 1076:1088 The formation of this mineral phase 1076:1110 The formation of this mineral phase is independent of the background solution but U(VI) luminescence lifetime analyses demonstrated that the U(VI) speciation in seawater samples is more intricate, i.e., different complexes were formed under natural conditions. 24618567 6 105 theme phosphate 1741:1749 arg1 groups 1751:1756 organic phosphate groups 1733:1756 organic phosphate groups at pH 2 1733:1764 The LIII-edge XAS and TRLFS studies showed that the biosorption process observed is dependent of pH. The bacterial cell forms a complex with U through organic phosphate groups at pH 2 and via phosphate and carboxyl groups at pH 3 and 4.3, respectively. 24618567 4 106 theme natural 1317:1323 arg1 conditions 1325:1334 natural conditions 1317:1334 natural conditions 1317:1334 The formation of this mineral phase is independent of the background solution but U(VI) luminescence lifetime analyses demonstrated that the U(VI) speciation in seawater samples is more intricate, i.e., different complexes were formed under natural conditions. 24618567 0 107 theme marine 331:336 arg1 MAH1 370:373 the marine bacterium Idiomarina loihiensis MAH1 327:373 the marine bacterium Idiomarina loihiensis MAH1 327:373 Biosorption and Biomineralization of U(VI) by the marine bacterium Idiomarina loihiensis MAH1: effect of background electrolyte and pH. The main goal of this study is to compare the effects of pH, uranium concentration, and background electrolyte (seawater and NaClO4 solution) on the speciation of uranium(VI) associated with the marine bacterium Idiomarina loihiensis MAH1. 24618567 2 108 dep mechanism 667:675 arg1 VI 641:642 VI 641:642 VI 641:642 We showed that the U(VI)/bacterium interaction mechanism is highly dependent upon pH but also the nature of the used background electrolyte played a role. 24618567 7 109 theme chemical 2089:2096 arg1 composition 2098:2108 the chemical composition 2085:2108 the chemical composition of the solution 2085:2124 The differences in the complexes formed between uranium and bacteria on seawater compared to NaClO4 solution demonstrates that the actinide/microbe interactions are influenced by the three studied factors, i.e., the pH, the uranium concentration and the chemical composition of the solution. 24618567 1 110 theme Absorption 464:473 arg1 XAS 489:491 XAS 489:491 XAS 489:491 This was done at the molecular level using a multidisciplinary approach combining X-ray Absorption Spectroscopy (XAS), Time-Resolved Laser-Induced Fluorescence Spectroscopy (TRLFS), and High Resolution Transmission Electron Microscopy (HRTEM). 24618567 1 110 theme Absorption 464:473 arg1 Spectroscopy 475:486 X-ray Absorption Spectroscopy 458:486 X-ray Absorption Spectroscopy (XAS) 458:492 This was done at the molecular level using a multidisciplinary approach combining X-ray Absorption Spectroscopy (XAS), Time-Resolved Laser-Induced Fluorescence Spectroscopy (TRLFS), and High Resolution Transmission Electron Microscopy (HRTEM). 24618567 5 111 theme U 1449:1449 arg1 evident 1555:1561 evident 1555:1561 evident 1555:1561 At acidic conditions, pH 2, 3 and 4.3 ([U] = 5·10(-4) M, background electrolyte = 0.1 M NaClO4), the removal of U from solution was due to biosorption to Extracellular Polysaccharides (EPS) and cell wall components as evident from TEM analysis. 24618567 5 111 theme U 1449:1449 arg1 removal 1438:1444 the removal 1434:1444 the removal of U from solution 1434:1463 At acidic conditions, pH 2, 3 and 4.3 ([U] = 5·10(-4) M, background electrolyte = 0.1 M NaClO4), the removal of U from solution was due to biosorption to Extracellular Polysaccharides (EPS) and cell wall components as evident from TEM analysis. 24618567 0 112 theme Idiomarina 348:357 arg1 MAH1 370:373 the marine bacterium Idiomarina loihiensis MAH1 327:373 the marine bacterium Idiomarina loihiensis MAH1 327:373 Biosorption and Biomineralization of U(VI) by the marine bacterium Idiomarina loihiensis MAH1: effect of background electrolyte and pH. The main goal of this study is to compare the effects of pH, uranium concentration, and background electrolyte (seawater and NaClO4 solution) on the speciation of uranium(VI) associated with the marine bacterium Idiomarina loihiensis MAH1. 28167931 9 0 from decrease 1184:1191 arg1 bioavailability 1201:1215 iron bioavailability 1196:1215 iron bioavailability 1196:1215 The slight decrease in iron bioavailability generated by SAL was enough to induce the increase of PIA expression in biofilms formed by methicillin-resistant as well as methicillin-sensitive S. aureus strains. 28167931 6 1 theme free 860:863 arg1 concentration 870:882 the intracellular free Fe2+ concentration 842:882 the intracellular free Fe2+ concentration 842:882 The exposure of biofilm to 2 mM SAL induced a 27% reduction in the intracellular free Fe2+ concentration compared with the controls. 28167931 16 2 theme SAL-induced 2141:2151 arg1 biofilms 2153:2160 SAL-induced biofilms 2141:2160 SAL-induced biofilms 2141:2160 SAL-induced biofilms may contribute to S. aureus infection persistence in vegetarian individuals as well as in patients that frequently consume aspirin. 28167931 12 3 theme spectroscopic 1714:1726 arg1 analysis 1728:1735 FTIR spectroscopic analysis 1709:1735 FTIR spectroscopic analysis 1709:1735 The polysaccharide composition of S. aureus biofilms was examined and FTIR spectroscopic analysis revealed a clear impact of SAL in a codY-dependent manner. 28167931 11 4 theme forming 1621:1627 arg1 biofilms 1629:1636 bacteria forming biofilms 1612:1636 bacteria forming biofilms 1612:1636 Furthermore, SAL diminished aconitase activity and stimulated the lactic fermentation pathway in bacteria forming biofilms. 28167931 6 5 from reduction 829:837 arg1 concentration 870:882 the intracellular free Fe2+ concentration 842:882 the intracellular free Fe2+ concentration 842:882 The exposure of biofilm to 2 mM SAL induced a 27% reduction in the intracellular free Fe2+ concentration compared with the controls. 28167931 1 6 theme human 164:168 arg1 health 170:175 human health 164:175 human health 164:175 Aspirin has provided clear benefits to human health. 28167931 5 7 theme content 594:600 arg1 limitation 602:611 the iron content limitation 585:611 the iron content limitation caused by SAL 585:625 The aim of this study was to elucidate whether the iron content limitation caused by SAL can modify the S. aureus metabolism and/or metabolic regulators thus changing the expression of the main polysaccharides involved in biofilm formation. 28167931 13 8 theme ica 1910:1912 arg1 operon 1914:1919 the ica operon 1906:1919 the ica operon 1906:1919 Moreover, SAL negatively affected codY transcription in mature biofilms thus relieving the CodY repression of the ica operon. 28167931 0 9 theme PIA-dependent 103:115 arg1 Manner 117:122 a PIA-dependent Manner 101:122 a PIA-dependent Manner 101:122 The Active Component of Aspirin, Salicylic Acid, Promotes Staphylococcus aureus Biofilm Formation in a PIA-dependent Manner. 28167931 15 10 theme high 2099:2102 arg1 colonization 2110:2121 the high nasal colonization 2095:2121 the high nasal colonization observed in mice 2095:2138 It is suggested that the elevated PIA expression induced by SAL might be responsible for the high nasal colonization observed in mice. 28167931 4 11 theme iron 416:419 arg1 cations 421:427 iron cations 416:427 iron cations 416:427 SAL can also form complexes with iron cations and it has been shown that different iron chelating molecules diminished the formation of S. aureus biofilm. 28167931 5 12 theme metabolic 670:678 arg1 regulators 680:689 metabolic regulators 670:689 metabolic regulators 670:689 The aim of this study was to elucidate whether the iron content limitation caused by SAL can modify the S. aureus metabolism and/or metabolic regulators thus changing the expression of the main polysaccharides involved in biofilm formation. 28167931 2 13 theme -the 203:206 arg1 biometabolite- 221:234 But salicylic acid (SAL) -the main aspirin biometabolite- 178:234 biometabolite- 221:234 But salicylic acid (SAL) -the main aspirin biometabolite- exerts several effects on eukaryote and prokaryote cells. 28167931 7 14 theme Fe2+ 964:967 arg1 cation 969:974 the available free Fe2+ cation 945:974 the available free Fe2+ cation 945:974 In addition, SAL depleted 23% of the available free Fe2+ cation in culture media. 28167931 9 15 theme iron 1196:1199 arg1 bioavailability 1201:1215 iron bioavailability 1196:1215 iron bioavailability 1196:1215 The slight decrease in iron bioavailability generated by SAL was enough to induce the increase of PIA expression in biofilms formed by methicillin-resistant as well as methicillin-sensitive S. aureus strains. 28167931 12 16 theme biofilms 1683:1690 arg1 composition 1658:1668 The polysaccharide composition 1639:1668 The polysaccharide composition of S. aureus biofilms 1639:1690 The polysaccharide composition of S. aureus biofilms was examined and FTIR spectroscopic analysis revealed a clear impact of SAL in a codY-dependent manner. 28167931 14 17 with Treatment 1922:1930 arg1 SAL 1945:1947 SAL 1945:1947 SAL 1945:1947 Treatment of mice with SAL induced a significant increase of S aureus colonization. 28167931 2 18 theme aspirin 213:219 arg1 biometabolite- 221:234 But salicylic acid (SAL) -the main aspirin biometabolite- 178:234 biometabolite- 221:234 But salicylic acid (SAL) -the main aspirin biometabolite- exerts several effects on eukaryote and prokaryote cells. 28167931 4 19 theme different 456:464 arg1 molecules 481:489 different iron chelating molecules 456:489 different iron chelating molecules 456:489 SAL can also form complexes with iron cations and it has been shown that different iron chelating molecules diminished the formation of S. aureus biofilm. 28167931 5 20 theme S. 642:643 arg1 metabolism 652:661 the S. aureus metabolism 638:661 the S. aureus metabolism 638:661 The aim of this study was to elucidate whether the iron content limitation caused by SAL can modify the S. aureus metabolism and/or metabolic regulators thus changing the expression of the main polysaccharides involved in biofilm formation. 28167931 13 21 theme mature 1852:1857 arg1 biofilms 1859:1866 mature biofilms 1852:1866 mature biofilms 1852:1866 Moreover, SAL negatively affected codY transcription in mature biofilms thus relieving the CodY repression of the ica operon. 28167931 0 22 theme Staphylococcus 58:71 arg1 Formation 88:96 Staphylococcus aureus Biofilm Formation 58:96 Staphylococcus aureus Biofilm Formation 58:96 The Active Component of Aspirin, Salicylic Acid, Promotes Staphylococcus aureus Biofilm Formation in a PIA-dependent Manner. 28167931 5 23 theme study 554:558 arg1 aim 542:544 The aim 538:544 The aim of this study 538:558 The aim of this study was to elucidate whether the iron content limitation caused by SAL can modify the S. aureus metabolism and/or metabolic regulators thus changing the expression of the main polysaccharides involved in biofilm formation. 28167931 4 24 theme chelating 471:479 arg1 molecules 481:489 different iron chelating molecules 456:489 different iron chelating molecules 456:489 SAL can also form complexes with iron cations and it has been shown that different iron chelating molecules diminished the formation of S. aureus biofilm. 28167931 0 25 theme Biofilm 80:86 arg1 Formation 88:96 Staphylococcus aureus Biofilm Formation 58:96 Staphylococcus aureus Biofilm Formation 58:96 The Active Component of Aspirin, Salicylic Acid, Promotes Staphylococcus aureus Biofilm Formation in a PIA-dependent Manner. 28167931 16 26 theme aureus 2183:2188 arg1 persistence 2200:2210 S. aureus infection persistence 2180:2210 S. aureus infection persistence 2180:2210 SAL-induced biofilms may contribute to S. aureus infection persistence in vegetarian individuals as well as in patients that frequently consume aspirin. 28167931 14 27 theme significant 1959:1969 arg1 increase 1971:1978 a significant increase 1957:1978 a significant increase of S aureus colonization 1957:2003 Treatment of mice with SAL induced a significant increase of S aureus colonization. 28167931 3 28 theme aureus 357:362 arg1 factors 374:380 Staphylococcus aureus virulence factors 342:380 Staphylococcus aureus virulence factors 342:380 SAL can affect, for instance, the expression of Staphylococcus aureus virulence factors. 28167931 0 29 dep Staphylococcus 58:71 arg1 aureus 73:78 aureus 73:78 aureus 73:78 The Active Component of Aspirin, Salicylic Acid, Promotes Staphylococcus aureus Biofilm Formation in a PIA-dependent Manner. 28167931 4 30 theme S. 519:520 arg1 biofilm 529:535 S. aureus biofilm 519:535 S. aureus biofilm 519:535 SAL can also form complexes with iron cations and it has been shown that different iron chelating molecules diminished the formation of S. aureus biofilm. 28167931 16 31 theme vegetarian 2215:2224 arg1 individuals 2226:2236 vegetarian individuals 2215:2236 vegetarian individuals 2215:2236 SAL-induced biofilms may contribute to S. aureus infection persistence in vegetarian individuals as well as in patients that frequently consume aspirin. 28167931 9 32 theme PIA 1271:1273 arg1 expression 1275:1284 PIA expression 1271:1284 PIA expression 1271:1284 The slight decrease in iron bioavailability generated by SAL was enough to induce the increase of PIA expression in biofilms formed by methicillin-resistant as well as methicillin-sensitive S. aureus strains. 28167931 8 33 theme moderate 1000:1007 arg1 conditions 1022:1031 These moderate iron-limited conditions 994:1031 These moderate iron-limited conditions 994:1031 These moderate iron-limited conditions promoted an intensification of biofilms formed by strain Newman and by S. aureus clinical isolates related to the USA300 and USA100 clones. 28167931 4 34 theme biofilm 529:535 arg1 formation 506:514 the formation 502:514 the formation of S. aureus biofilm 502:535 SAL can also form complexes with iron cations and it has been shown that different iron chelating molecules diminished the formation of S. aureus biofilm. 28167931 0 35 theme Aspirin 24:30 arg1 Component 11:19 The Active Component 0:19 The Active Component of Aspirin 0:30 The Active Component of Aspirin, Salicylic Acid, Promotes Staphylococcus aureus Biofilm Formation in a PIA-dependent Manner. 28167931 0 35 theme Aspirin 24:30 arg1 Acid 43:46 Salicylic Acid 33:46 Salicylic Acid 33:46 The Active Component of Aspirin, Salicylic Acid, Promotes Staphylococcus aureus Biofilm Formation in a PIA-dependent Manner. 28167931 10 36 theme experimental 1483:1494 arg1 conditions 1496:1505 the experimental conditions 1479:1505 the experimental conditions tested 1479:1512 S. aureus did not produce capsular polysaccharide (CP) when it was forming biofilms under any of the experimental conditions tested. 28167931 3 37 theme factors 374:380 arg1 expression 328:337 the expression 324:337 the expression of Staphylococcus aureus virulence factors 324:380 SAL can affect, for instance, the expression of Staphylococcus aureus virulence factors. 28167931 5 38 theme biofilm 760:766 arg1 formation 768:776 biofilm formation 760:776 biofilm formation 760:776 The aim of this study was to elucidate whether the iron content limitation caused by SAL can modify the S. aureus metabolism and/or metabolic regulators thus changing the expression of the main polysaccharides involved in biofilm formation. 28167931 6 39 theme 2 806:806 arg1 mM 808:809 mM 808:809 mM 808:809 The exposure of biofilm to 2 mM SAL induced a 27% reduction in the intracellular free Fe2+ concentration compared with the controls. 28167931 14 40 theme colonization 1992:2003 arg1 increase 1971:1978 a significant increase 1957:1978 a significant increase of S aureus colonization 1957:2003 Treatment of mice with SAL induced a significant increase of S aureus colonization. 28167931 2 41 theme acid 192:195 arg1 biometabolite- 221:234 But salicylic acid (SAL) -the main aspirin biometabolite- 178:234 biometabolite- 221:234 But salicylic acid (SAL) -the main aspirin biometabolite- exerts several effects on eukaryote and prokaryote cells. 28167931 6 42 theme biofilm 795:801 arg1 exposure 783:790 The exposure 779:790 The exposure of biofilm to 2 mM SAL 779:813 The exposure of biofilm to 2 mM SAL induced a 27% reduction in the intracellular free Fe2+ concentration compared with the controls. 28167931 13 43 from transcription 1835:1847 arg1 biofilms 1859:1866 mature biofilms 1852:1866 mature biofilms 1852:1866 Moreover, SAL negatively affected codY transcription in mature biofilms thus relieving the CodY repression of the ica operon. 28167931 6 44 theme Fe2+ 865:868 arg1 concentration 870:882 the intracellular free Fe2+ concentration 842:882 the intracellular free Fe2+ concentration 842:882 The exposure of biofilm to 2 mM SAL induced a 27% reduction in the intracellular free Fe2+ concentration compared with the controls. 28167931 15 45 theme PIA 2040:2042 arg1 expression 2044:2053 the elevated PIA expression 2027:2053 the elevated PIA expression induced by SAL 2027:2068 It is suggested that the elevated PIA expression induced by SAL might be responsible for the high nasal colonization observed in mice. 28167931 15 45 theme PIA 2040:2042 arg1 responsible 2079:2089 responsible 2079:2089 responsible 2079:2089 It is suggested that the elevated PIA expression induced by SAL might be responsible for the high nasal colonization observed in mice. 28167931 12 46 theme SAL 1764:1766 arg1 impact 1754:1759 a clear impact 1746:1759 a clear impact of SAL 1746:1766 The polysaccharide composition of S. aureus biofilms was examined and FTIR spectroscopic analysis revealed a clear impact of SAL in a codY-dependent manner. 28167931 11 47 theme bacteria 1612:1619 arg1 biofilms 1629:1636 bacteria forming biofilms 1612:1636 bacteria forming biofilms 1612:1636 Furthermore, SAL diminished aconitase activity and stimulated the lactic fermentation pathway in bacteria forming biofilms. 28167931 9 48 theme methicillin-sensitive 1341:1361 arg1 strains 1373:1379 methicillin-sensitive S. aureus strains 1341:1379 methicillin-resistant as well as methicillin-sensitive S. aureus strains 1308:1379 The slight decrease in iron bioavailability generated by SAL was enough to induce the increase of PIA expression in biofilms formed by methicillin-resistant as well as methicillin-sensitive S. aureus strains. 28167931 8 49 theme strain 1083:1088 arg1 Newman 1090:1095 strain Newman 1083:1095 strain Newman 1083:1095 These moderate iron-limited conditions promoted an intensification of biofilms formed by strain Newman and by S. aureus clinical isolates related to the USA300 and USA100 clones. 28167931 6 50 theme intracellular 846:858 arg1 concentration 870:882 the intracellular free Fe2+ concentration 842:882 the intracellular free Fe2+ concentration 842:882 The exposure of biofilm to 2 mM SAL induced a 27% reduction in the intracellular free Fe2+ concentration compared with the controls. 28167931 11 51 theme lactic 1581:1586 arg1 pathway 1601:1607 the lactic fermentation pathway 1577:1607 the lactic fermentation pathway in bacteria forming biofilms 1577:1636 Furthermore, SAL diminished aconitase activity and stimulated the lactic fermentation pathway in bacteria forming biofilms. 28167931 9 52 theme aureus 1366:1371 arg1 strains 1373:1379 methicillin-sensitive S. aureus strains 1341:1379 methicillin-resistant as well as methicillin-sensitive S. aureus strains 1308:1379 The slight decrease in iron bioavailability generated by SAL was enough to induce the increase of PIA expression in biofilms formed by methicillin-resistant as well as methicillin-sensitive S. aureus strains. 28167931 16 53 theme S. 2180:2181 arg1 persistence 2200:2210 S. aureus infection persistence 2180:2210 S. aureus infection persistence 2180:2210 SAL-induced biofilms may contribute to S. aureus infection persistence in vegetarian individuals as well as in patients that frequently consume aspirin. 28167931 8 54 theme S. 1104:1105 arg1 isolates 1123:1130 S. aureus clinical isolates 1104:1130 S. aureus clinical isolates related to the USA300 and USA100 clones 1104:1170 These moderate iron-limited conditions promoted an intensification of biofilms formed by strain Newman and by S. aureus clinical isolates related to the USA300 and USA100 clones. 28167931 6 55 theme % 827:827 arg1 reduction 829:837 a 27% reduction 823:837 a 27% reduction in the intracellular free Fe2+ concentration 823:882 The exposure of biofilm to 2 mM SAL induced a 27% reduction in the intracellular free Fe2+ concentration compared with the controls. 28167931 5 56 theme main 727:730 arg1 polysaccharides 732:746 the main polysaccharides 723:746 the main polysaccharides involved in biofilm formation 723:776 The aim of this study was to elucidate whether the iron content limitation caused by SAL can modify the S. aureus metabolism and/or metabolic regulators thus changing the expression of the main polysaccharides involved in biofilm formation. 28167931 5 57 theme iron 589:592 arg1 limitation 602:611 the iron content limitation 585:611 the iron content limitation caused by SAL 585:625 The aim of this study was to elucidate whether the iron content limitation caused by SAL can modify the S. aureus metabolism and/or metabolic regulators thus changing the expression of the main polysaccharides involved in biofilm formation. 28167931 15 58 theme nasal 2104:2108 arg1 colonization 2110:2121 the high nasal colonization 2095:2121 the high nasal colonization observed in mice 2095:2138 It is suggested that the elevated PIA expression induced by SAL might be responsible for the high nasal colonization observed in mice. 28167931 8 59 theme clinical 1114:1121 arg1 isolates 1123:1130 S. aureus clinical isolates 1104:1130 S. aureus clinical isolates related to the USA300 and USA100 clones 1104:1170 These moderate iron-limited conditions promoted an intensification of biofilms formed by strain Newman and by S. aureus clinical isolates related to the USA300 and USA100 clones. 28167931 12 60 theme FTIR 1709:1712 arg1 analysis 1728:1735 FTIR spectroscopic analysis 1709:1735 FTIR spectroscopic analysis 1709:1735 The polysaccharide composition of S. aureus biofilms was examined and FTIR spectroscopic analysis revealed a clear impact of SAL in a codY-dependent manner. 28167931 0 61 theme Salicylic 33:41 arg1 Component 11:19 The Active Component 0:19 The Active Component of Aspirin 0:30 The Active Component of Aspirin, Salicylic Acid, Promotes Staphylococcus aureus Biofilm Formation in a PIA-dependent Manner. 28167931 0 61 theme Salicylic 33:41 arg1 Acid 43:46 Salicylic Acid 33:46 Salicylic Acid 33:46 The Active Component of Aspirin, Salicylic Acid, Promotes Staphylococcus aureus Biofilm Formation in a PIA-dependent Manner. 28167931 5 62 theme aureus 645:650 arg1 metabolism 652:661 the S. aureus metabolism 638:661 the S. aureus metabolism 638:661 The aim of this study was to elucidate whether the iron content limitation caused by SAL can modify the S. aureus metabolism and/or metabolic regulators thus changing the expression of the main polysaccharides involved in biofilm formation. 28167931 13 63 theme operon 1914:1919 arg1 repression 1892:1901 the CodY repression 1883:1901 the CodY repression of the ica operon 1883:1919 Moreover, SAL negatively affected codY transcription in mature biofilms thus relieving the CodY repression of the ica operon. 28167931 8 64 theme related 1132:1138 arg1 isolates 1123:1130 S. aureus clinical isolates 1104:1130 S. aureus clinical isolates related to the USA300 and USA100 clones 1104:1170 These moderate iron-limited conditions promoted an intensification of biofilms formed by strain Newman and by S. aureus clinical isolates related to the USA300 and USA100 clones. 28167931 7 65 theme culture 979:985 arg1 media 987:991 culture media 979:991 culture media 979:991 In addition, SAL depleted 23% of the available free Fe2+ cation in culture media. 28167931 2 66 theme main 208:211 arg1 biometabolite- 221:234 But salicylic acid (SAL) -the main aspirin biometabolite- 178:234 biometabolite- 221:234 But salicylic acid (SAL) -the main aspirin biometabolite- exerts several effects on eukaryote and prokaryote cells. 28167931 7 67 theme cation 969:974 arg1 cation 969:974 the available free Fe2+ cation 945:974 the available free Fe2+ cation 945:974 In addition, SAL depleted 23% of the available free Fe2+ cation in culture media. 28167931 7 67 theme cation 969:974 arg1 % 940:940 23% 938:940 23% of the available free Fe2+ cation 938:974 In addition, SAL depleted 23% of the available free Fe2+ cation in culture media. 28167931 9 68 theme slight 1177:1182 arg1 decrease 1184:1191 The slight decrease 1173:1191 The slight decrease in iron bioavailability generated by SAL 1173:1232 The slight decrease in iron bioavailability generated by SAL was enough to induce the increase of PIA expression in biofilms formed by methicillin-resistant as well as methicillin-sensitive S. aureus strains. 28167931 7 69 theme available 949:957 arg1 cation 969:974 the available free Fe2+ cation 945:974 the available free Fe2+ cation 945:974 In addition, SAL depleted 23% of the available free Fe2+ cation in culture media. 28167931 7 70 theme free 959:962 arg1 cation 969:974 the available free Fe2+ cation 945:974 the available free Fe2+ cation 945:974 In addition, SAL depleted 23% of the available free Fe2+ cation in culture media. 28167931 2 71 theme several 243:249 arg1 effects 251:257 several effects 243:257 several effects 243:257 But salicylic acid (SAL) -the main aspirin biometabolite- exerts several effects on eukaryote and prokaryote cells. 28167931 13 72 theme CodY 1887:1890 arg1 repression 1892:1901 the CodY repression 1883:1901 the CodY repression of the ica operon 1883:1919 Moreover, SAL negatively affected codY transcription in mature biofilms thus relieving the CodY repression of the ica operon. 28167931 12 73 theme aureus 1676:1681 arg1 biofilms 1683:1690 S. aureus biofilms 1673:1690 S. aureus biofilms 1673:1690 The polysaccharide composition of S. aureus biofilms was examined and FTIR spectroscopic analysis revealed a clear impact of SAL in a codY-dependent manner. 28167931 4 74 theme iron 466:469 arg1 molecules 481:489 different iron chelating molecules 456:489 different iron chelating molecules 456:489 SAL can also form complexes with iron cations and it has been shown that different iron chelating molecules diminished the formation of S. aureus biofilm. 28167931 1 75 theme clear 146:150 arg1 benefits 152:159 clear benefits 146:159 clear benefits 146:159 Aspirin has provided clear benefits to human health. 28167931 8 76 dep S. 1104:1105 arg1 aureus 1107:1112 aureus 1107:1112 aureus 1107:1112 These moderate iron-limited conditions promoted an intensification of biofilms formed by strain Newman and by S. aureus clinical isolates related to the USA300 and USA100 clones. 28167931 2 77 dep eukaryote 262:270 arg1 cells 287:291 cells 287:291 cells 287:291 But salicylic acid (SAL) -the main aspirin biometabolite- exerts several effects on eukaryote and prokaryote cells. 28167931 14 78 theme S 1983:1983 arg1 colonization 1992:2003 S aureus colonization 1983:2003 S aureus colonization 1983:2003 Treatment of mice with SAL induced a significant increase of S aureus colonization. 28167931 12 79 theme polysaccharide 1643:1656 arg1 composition 1658:1668 The polysaccharide composition 1639:1668 The polysaccharide composition of S. aureus biofilms 1639:1690 The polysaccharide composition of S. aureus biofilms was examined and FTIR spectroscopic analysis revealed a clear impact of SAL in a codY-dependent manner. 28167931 16 80 theme infection 2190:2198 arg1 persistence 2200:2210 S. aureus infection persistence 2180:2210 S. aureus infection persistence 2180:2210 SAL-induced biofilms may contribute to S. aureus infection persistence in vegetarian individuals as well as in patients that frequently consume aspirin. 28167931 10 81 theme capsular 1408:1415 arg1 CP 1433:1434 CP 1433:1434 CP 1433:1434 S. aureus did not produce capsular polysaccharide (CP) when it was forming biofilms under any of the experimental conditions tested. 28167931 10 81 theme capsular 1408:1415 arg1 polysaccharide 1417:1430 capsular polysaccharide 1408:1430 capsular polysaccharide (CP) 1408:1435 S. aureus did not produce capsular polysaccharide (CP) when it was forming biofilms under any of the experimental conditions tested. 28167931 13 82 theme codY 1830:1833 arg1 transcription 1835:1847 codY transcription 1830:1847 codY transcription in mature biofilms 1830:1866 Moreover, SAL negatively affected codY transcription in mature biofilms thus relieving the CodY repression of the ica operon. 28167931 0 83 theme Active 4:9 arg1 Component 11:19 The Active Component 0:19 The Active Component of Aspirin 0:30 The Active Component of Aspirin, Salicylic Acid, Promotes Staphylococcus aureus Biofilm Formation in a PIA-dependent Manner. 28167931 0 83 theme Active 4:9 arg1 Acid 43:46 Salicylic Acid 33:46 Salicylic Acid 33:46 The Active Component of Aspirin, Salicylic Acid, Promotes Staphylococcus aureus Biofilm Formation in a PIA-dependent Manner. 28167931 9 84 from increase 1259:1266 arg1 biofilms 1289:1296 biofilms 1289:1296 biofilms formed by methicillin-resistant as well as methicillin-sensitive S. aureus strains 1289:1379 The slight decrease in iron bioavailability generated by SAL was enough to induce the increase of PIA expression in biofilms formed by methicillin-resistant as well as methicillin-sensitive S. aureus strains. 28167931 3 85 theme virulence 364:372 arg1 factors 374:380 Staphylococcus aureus virulence factors 342:380 Staphylococcus aureus virulence factors 342:380 SAL can affect, for instance, the expression of Staphylococcus aureus virulence factors. 28167931 4 86 theme aureus 522:527 arg1 biofilm 529:535 S. aureus biofilm 519:535 S. aureus biofilm 519:535 SAL can also form complexes with iron cations and it has been shown that different iron chelating molecules diminished the formation of S. aureus biofilm. 28167931 8 87 theme iron-limited 1009:1020 arg1 conditions 1022:1031 These moderate iron-limited conditions 994:1031 These moderate iron-limited conditions 994:1031 These moderate iron-limited conditions promoted an intensification of biofilms formed by strain Newman and by S. aureus clinical isolates related to the USA300 and USA100 clones. 28167931 3 88 theme Staphylococcus 342:355 arg1 factors 374:380 Staphylococcus aureus virulence factors 342:380 Staphylococcus aureus virulence factors 342:380 SAL can affect, for instance, the expression of Staphylococcus aureus virulence factors. 28167931 4 89 with complexes 401:409 arg1 cations 421:427 iron cations 416:427 iron cations 416:427 SAL can also form complexes with iron cations and it has been shown that different iron chelating molecules diminished the formation of S. aureus biofilm. 28167931 5 90 theme polysaccharides 732:746 arg1 expression 709:718 the expression 705:718 the expression of the main polysaccharides involved in biofilm formation 705:776 The aim of this study was to elucidate whether the iron content limitation caused by SAL can modify the S. aureus metabolism and/or metabolic regulators thus changing the expression of the main polysaccharides involved in biofilm formation. 28167931 9 91 theme expression 1275:1284 arg1 increase 1259:1266 the increase 1255:1266 the increase of PIA expression in biofilms formed by methicillin-resistant as well as methicillin-sensitive S. aureus strains 1255:1379 The slight decrease in iron bioavailability generated by SAL was enough to induce the increase of PIA expression in biofilms formed by methicillin-resistant as well as methicillin-sensitive S. aureus strains. 28167931 14 92 theme mice 1935:1938 arg1 Treatment 1922:1930 Treatment 1922:1930 Treatment of mice with SAL 1922:1947 Treatment of mice with SAL induced a significant increase of S aureus colonization. 28167931 6 93 theme mM 808:809 arg1 SAL 811:813 2 mM SAL 806:813 2 mM SAL 806:813 The exposure of biofilm to 2 mM SAL induced a 27% reduction in the intracellular free Fe2+ concentration compared with the controls. 28167931 11 94 from pathway 1601:1607 arg1 biofilms 1629:1636 bacteria forming biofilms 1612:1636 bacteria forming biofilms 1612:1636 Furthermore, SAL diminished aconitase activity and stimulated the lactic fermentation pathway in bacteria forming biofilms. 28167931 10 95 theme forming 1449:1455 arg1 biofilms 1457:1464 forming biofilms 1449:1464 forming biofilms 1449:1464 S. aureus did not produce capsular polysaccharide (CP) when it was forming biofilms under any of the experimental conditions tested. 28167931 8 96 theme biofilms 1064:1071 arg1 intensification 1045:1059 an intensification 1042:1059 an intensification of biofilms formed by strain Newman and by S. aureus clinical isolates related to the USA300 and USA100 clones 1042:1170 These moderate iron-limited conditions promoted an intensification of biofilms formed by strain Newman and by S. aureus clinical isolates related to the USA300 and USA100 clones. 28167931 15 97 located observed 2123:2130 arg1 mice 2135:2138 mice 2135:2138 mice 2135:2138 It is suggested that the elevated PIA expression induced by SAL might be responsible for the high nasal colonization observed in mice. 28167931 15 97 located observed 2123:2130 arg2 colonization 2110:2121 the high nasal colonization 2095:2121 the high nasal colonization observed in mice 2095:2138 It is suggested that the elevated PIA expression induced by SAL might be responsible for the high nasal colonization observed in mice. 28167931 12 98 theme codY-dependent 1773:1786 arg1 manner 1788:1793 a codY-dependent manner 1771:1793 a codY-dependent manner 1771:1793 The polysaccharide composition of S. aureus biofilms was examined and FTIR spectroscopic analysis revealed a clear impact of SAL in a codY-dependent manner. 28167931 14 99 theme aureus 1985:1990 arg1 colonization 1992:2003 S aureus colonization 1983:2003 S aureus colonization 1983:2003 Treatment of mice with SAL induced a significant increase of S aureus colonization. 28167931 2 100 theme salicylic 182:190 arg1 SAL 198:200 SAL 198:200 SAL 198:200 But salicylic acid (SAL) -the main aspirin biometabolite- exerts several effects on eukaryote and prokaryote cells. 28167931 2 100 theme salicylic 182:190 arg1 acid 192:195 salicylic acid 182:195 salicylic acid (SAL) 182:201 But salicylic acid (SAL) -the main aspirin biometabolite- exerts several effects on eukaryote and prokaryote cells. 28167931 15 101 theme elevated 2031:2038 arg1 expression 2044:2053 the elevated PIA expression 2027:2053 the elevated PIA expression induced by SAL 2027:2068 It is suggested that the elevated PIA expression induced by SAL might be responsible for the high nasal colonization observed in mice. 28167931 15 101 theme elevated 2031:2038 arg1 responsible 2079:2089 responsible 2079:2089 responsible 2079:2089 It is suggested that the elevated PIA expression induced by SAL might be responsible for the high nasal colonization observed in mice. 28167931 12 102 theme clear 1748:1752 arg1 impact 1754:1759 a clear impact 1746:1759 a clear impact of SAL 1746:1766 The polysaccharide composition of S. aureus biofilms was examined and FTIR spectroscopic analysis revealed a clear impact of SAL in a codY-dependent manner. 28167931 11 103 theme fermentation 1588:1599 arg1 pathway 1601:1607 the lactic fermentation pathway 1577:1607 the lactic fermentation pathway in bacteria forming biofilms 1577:1636 Furthermore, SAL diminished aconitase activity and stimulated the lactic fermentation pathway in bacteria forming biofilms. 28167931 11 104 theme aconitase 1543:1551 arg1 activity 1553:1560 aconitase activity 1543:1560 aconitase activity 1543:1560 Furthermore, SAL diminished aconitase activity and stimulated the lactic fermentation pathway in bacteria forming biofilms. 24959350 5 0 theme combined 509:516 arg1 sequencing 525:534 PCR combined direct sequencing 505:534 PCR combined direct sequencing 505:534 In 55 healthy subjects, SAA4 polymorphism was analyzed by PCR combined direct sequencing and its glycosylation status was analyzed by immunoblotting. 24959350 1 1 theme high-density 132:143 arg1 lipoprotein 145:155 high-density lipoprotein 132:155 high-density lipoprotein 132:155 Serum amyloid A4 (SAA4) is a constitutive apolipoprotein of high-density lipoprotein. 24959350 3 2 from forms 261:265 arg1 plasma 270:275 plasma 270:275 plasma 270:275 There are both glycosylated and nonglycosylated forms in plasma and the ratio of these two forms varies among individuals. 24959350 3 3 theme forms 304:308 arg1 ratio 285:289 the ratio 281:289 the ratio of these two forms 281:308 There are both glycosylated and nonglycosylated forms in plasma and the ratio of these two forms varies among individuals. 24959350 1 4 theme lipoprotein 145:155 arg1 A4 86:87 Serum amyloid A4 72:87 Serum amyloid A4 (SAA4) 72:94 Serum amyloid A4 (SAA4) is a constitutive apolipoprotein of high-density lipoprotein. 24959350 1 4 theme lipoprotein 145:155 arg1 apolipoprotein 114:127 a constitutive apolipoprotein 99:127 a constitutive apolipoprotein of high-density lipoprotein 99:155 Serum amyloid A4 (SAA4) is a constitutive apolipoprotein of high-density lipoprotein. 24959350 9 5 theme this 1022:1025 arg1 implication 1007:1017 The functional implication 992:1017 The functional implication of this 992:1025 The functional implication of this should be of interest. 24959350 4 6 theme glycosylation 425:437 arg1 status 439:444 its glycosylation status 421:444 its glycosylation status 421:444 This study was conducted to examine the influence of genetic polymorphism of SAA4 on its glycosylation status. 24959350 0 7 from Influence 0:8 arg1 glycosylation 29:41 glycosylation 29:41 glycosylation of serum amyloid a4 protein 29:69 Influence of polymorphism on glycosylation of serum amyloid a4 protein. 24959350 8 8 theme protein 913:919 arg1 structures 921:930 protein structures 913:930 protein structures 913:930 These findings suggest that the changes in protein structures alter the efficiency of glycosylation in the SAA4 molecule. 24959350 4 9 theme genetic 389:395 arg1 polymorphism 397:408 genetic polymorphism 389:408 genetic polymorphism of SAA4 389:416 This study was conducted to examine the influence of genetic polymorphism of SAA4 on its glycosylation status. 24959350 6 10 dep higher 750:755 arg1 < 742:742 P < 0.05 740:747 P < 0.05 740:747 The results showed that the percentage of glycosylation in subjects with amino acid substitutions at positions 71 and/or 84 was significantly (P < 0.05) higher than that in subjects with the wild type. 24959350 4 11 from influence 376:384 arg1 status 439:444 its glycosylation status 421:444 its glycosylation status 421:444 This study was conducted to examine the influence of genetic polymorphism of SAA4 on its glycosylation status. 24959350 5 12 theme SAA4 471:474 arg1 polymorphism 476:487 SAA4 polymorphism 471:487 SAA4 polymorphism 471:487 In 55 healthy subjects, SAA4 polymorphism was analyzed by PCR combined direct sequencing and its glycosylation status was analyzed by immunoblotting. 24959350 3 13 theme nonglycosylated 245:259 arg1 forms 261:265 both glycosylated and nonglycosylated forms 223:265 both glycosylated and nonglycosylated forms in plasma 223:275 There are both glycosylated and nonglycosylated forms in plasma and the ratio of these two forms varies among individuals. 24959350 5 14 theme glycosylation 544:556 arg1 status 558:563 its glycosylation status 540:563 its glycosylation status 540:563 In 55 healthy subjects, SAA4 polymorphism was analyzed by PCR combined direct sequencing and its glycosylation status was analyzed by immunoblotting. 24959350 1 15 theme Serum 72:76 arg1 A4 86:87 Serum amyloid A4 72:87 Serum amyloid A4 (SAA4) 72:94 Serum amyloid A4 (SAA4) is a constitutive apolipoprotein of high-density lipoprotein. 24959350 1 15 theme Serum 72:76 arg1 apolipoprotein 114:127 a constitutive apolipoprotein 99:127 a constitutive apolipoprotein of high-density lipoprotein 99:155 Serum amyloid A4 (SAA4) is a constitutive apolipoprotein of high-density lipoprotein. 24959350 1 15 theme Serum 72:76 arg1 SAA4 90:93 SAA4 90:93 SAA4 90:93 Serum amyloid A4 (SAA4) is a constitutive apolipoprotein of high-density lipoprotein. 24959350 3 16 gly nonglycosylated 245:259 arg1 forms 261:265 both glycosylated and nonglycosylated forms 223:265 both glycosylated and nonglycosylated forms in plasma 223:275 There are both glycosylated and nonglycosylated forms in plasma and the ratio of these two forms varies among individuals. 24959350 8 17 theme glycosylation 956:968 arg1 efficiency 942:951 the efficiency 938:951 the efficiency of glycosylation in the SAA4 molecule 938:989 These findings suggest that the changes in protein structures alter the efficiency of glycosylation in the SAA4 molecule. 24959350 1 18 theme amyloid 78:84 arg1 A4 86:87 Serum amyloid A4 72:87 Serum amyloid A4 (SAA4) 72:94 Serum amyloid A4 (SAA4) is a constitutive apolipoprotein of high-density lipoprotein. 24959350 1 18 theme amyloid 78:84 arg1 apolipoprotein 114:127 a constitutive apolipoprotein 99:127 a constitutive apolipoprotein of high-density lipoprotein 99:155 Serum amyloid A4 (SAA4) is a constitutive apolipoprotein of high-density lipoprotein. 24959350 1 18 theme amyloid 78:84 arg1 SAA4 90:93 SAA4 90:93 SAA4 90:93 Serum amyloid A4 (SAA4) is a constitutive apolipoprotein of high-density lipoprotein. 24959350 2 19 link N-linked 170:177 arg1 glycosylation 179:191 N-linked glycosylation 170:191 N-linked glycosylation 170:191 It exhibits N-linked glycosylation in its second half. 24959350 3 20 theme glycosylated 228:239 arg1 forms 261:265 both glycosylated and nonglycosylated forms 223:265 both glycosylated and nonglycosylated forms in plasma 223:275 There are both glycosylated and nonglycosylated forms in plasma and the ratio of these two forms varies among individuals. 24959350 8 21 theme SAA4 977:980 arg1 molecule 982:989 the SAA4 molecule 973:989 the SAA4 molecule 973:989 These findings suggest that the changes in protein structures alter the efficiency of glycosylation in the SAA4 molecule. 24959350 6 22 theme acid 676:679 arg1 substitutions 681:693 amino acid substitutions 670:693 amino acid substitutions at positions 71 and/or 84 670:719 The results showed that the percentage of glycosylation in subjects with amino acid substitutions at positions 71 and/or 84 was significantly (P < 0.05) higher than that in subjects with the wild type. 24959350 3 23 gly glycosylated 228:239 arg1 forms 261:265 both glycosylated and nonglycosylated forms 223:265 both glycosylated and nonglycosylated forms in plasma 223:275 There are both glycosylated and nonglycosylated forms in plasma and the ratio of these two forms varies among individuals. 24959350 6 24 theme amino 670:674 arg1 substitutions 681:693 amino acid substitutions 670:693 amino acid substitutions at positions 71 and/or 84 670:719 The results showed that the percentage of glycosylation in subjects with amino acid substitutions at positions 71 and/or 84 was significantly (P < 0.05) higher than that in subjects with the wild type. 24959350 0 25 theme polymorphism 13:24 arg1 Influence 0:8 Influence 0:8 Influence of polymorphism on glycosylation of serum amyloid a4 protein. 0:70 Influence of polymorphism on glycosylation of serum amyloid a4 protein. 24959350 2 26 theme N-linked 170:177 arg1 glycosylation 179:191 N-linked glycosylation 170:191 N-linked glycosylation 170:191 It exhibits N-linked glycosylation in its second half. 24959350 5 27 theme healthy 453:459 arg1 subjects 461:468 55 healthy subjects 450:468 55 healthy subjects 450:468 In 55 healthy subjects, SAA4 polymorphism was analyzed by PCR combined direct sequencing and its glycosylation status was analyzed by immunoblotting. 24959350 9 28 theme functional 996:1005 arg1 implication 1007:1017 The functional implication 992:1017 The functional implication of this 992:1025 The functional implication of this should be of interest. 24959350 6 29 from percentage 625:634 arg1 subjects 656:663 subjects 656:663 subjects with amino acid substitutions at positions 71 and/or 84 656:719 The results showed that the percentage of glycosylation in subjects with amino acid substitutions at positions 71 and/or 84 was significantly (P < 0.05) higher than that in subjects with the wild type. 24959350 5 30 theme direct 518:523 arg1 sequencing 525:534 PCR combined direct sequencing 505:534 PCR combined direct sequencing 505:534 In 55 healthy subjects, SAA4 polymorphism was analyzed by PCR combined direct sequencing and its glycosylation status was analyzed by immunoblotting. 24959350 8 31 from changes 902:908 arg1 structures 921:930 protein structures 913:930 protein structures 913:930 These findings suggest that the changes in protein structures alter the efficiency of glycosylation in the SAA4 molecule. 24959350 0 32 theme amyloid 52:58 arg1 protein 63:69 serum amyloid a4 protein 46:69 serum amyloid a4 protein 46:69 Influence of polymorphism on glycosylation of serum amyloid a4 protein. 24959350 7 33 contain had 816:818 arg2 influence 823:831 no influence 820:831 no influence 820:831 The polymorphism had no influence on the plasma concentration of SAA4. 24959350 7 33 contain had 816:818 arg1 polymorphism 803:814 The polymorphism 799:814 The polymorphism 799:814 The polymorphism had no influence on the plasma concentration of SAA4. 24959350 0 34 theme serum 46:50 arg1 protein 63:69 serum amyloid a4 protein 46:69 serum amyloid a4 protein 46:69 Influence of polymorphism on glycosylation of serum amyloid a4 protein. 24959350 6 35 with subjects 656:663 arg1 substitutions 681:693 amino acid substitutions 670:693 amino acid substitutions at positions 71 and/or 84 670:719 The results showed that the percentage of glycosylation in subjects with amino acid substitutions at positions 71 and/or 84 was significantly (P < 0.05) higher than that in subjects with the wild type. 24959350 2 36 theme second 200:205 arg1 half 207:210 its second half 196:210 its second half 196:210 It exhibits N-linked glycosylation in its second half. 24959350 6 37 theme P 740:740 arg1 < 742:742 P < 0.05 740:747 P < 0.05 740:747 The results showed that the percentage of glycosylation in subjects with amino acid substitutions at positions 71 and/or 84 was significantly (P < 0.05) higher than that in subjects with the wild type. 24959350 8 38 from efficiency 942:951 arg1 molecule 982:989 the SAA4 molecule 973:989 the SAA4 molecule 973:989 These findings suggest that the changes in protein structures alter the efficiency of glycosylation in the SAA4 molecule. 24959350 4 39 theme polymorphism 397:408 arg1 influence 376:384 the influence 372:384 the influence of genetic polymorphism of SAA4 on its glycosylation status 372:444 This study was conducted to examine the influence of genetic polymorphism of SAA4 on its glycosylation status. 24959350 0 40 gly glycosylation 29:41 arg1 protein 63:69 serum amyloid a4 protein 46:69 serum amyloid a4 protein 46:69 Influence of polymorphism on glycosylation of serum amyloid a4 protein. 24959350 6 41 theme glycosylation 639:651 arg1 higher 750:755 higher 750:755 higher 750:755 The results showed that the percentage of glycosylation in subjects with amino acid substitutions at positions 71 and/or 84 was significantly (P < 0.05) higher than that in subjects with the wild type. 24959350 6 41 theme glycosylation 639:651 arg1 percentage 625:634 the percentage 621:634 the percentage of glycosylation in subjects with amino acid substitutions at positions 71 and/or 84 621:719 The results showed that the percentage of glycosylation in subjects with amino acid substitutions at positions 71 and/or 84 was significantly (P < 0.05) higher than that in subjects with the wild type. 24959350 6 42 from positions 698:706 arg1 substitutions 681:693 amino acid substitutions 670:693 amino acid substitutions at positions 71 and/or 84 670:719 The results showed that the percentage of glycosylation in subjects with amino acid substitutions at positions 71 and/or 84 was significantly (P < 0.05) higher than that in subjects with the wild type. 24959350 1 43 theme constitutive 101:112 arg1 A4 86:87 Serum amyloid A4 72:87 Serum amyloid A4 (SAA4) 72:94 Serum amyloid A4 (SAA4) is a constitutive apolipoprotein of high-density lipoprotein. 24959350 1 43 theme constitutive 101:112 arg1 apolipoprotein 114:127 a constitutive apolipoprotein 99:127 a constitutive apolipoprotein of high-density lipoprotein 99:155 Serum amyloid A4 (SAA4) is a constitutive apolipoprotein of high-density lipoprotein. 24959350 2 44 gly glycosylation 179:191 arg1 half 207:210 its second half 196:210 its second half 196:210 It exhibits N-linked glycosylation in its second half. 24959350 0 45 theme protein 63:69 arg1 glycosylation 29:41 glycosylation 29:41 glycosylation of serum amyloid a4 protein 29:69 Influence of polymorphism on glycosylation of serum amyloid a4 protein. 24959350 4 46 theme SAA4 413:416 arg1 polymorphism 397:408 genetic polymorphism 389:408 genetic polymorphism of SAA4 389:416 This study was conducted to examine the influence of genetic polymorphism of SAA4 on its glycosylation status. 24959350 7 47 theme SAA4 864:867 arg1 concentration 847:859 the plasma concentration 836:859 the plasma concentration of SAA4 836:867 The polymorphism had no influence on the plasma concentration of SAA4. 24959350 6 48 theme wild 788:791 arg1 type 793:796 the wild type 784:796 the wild type 784:796 The results showed that the percentage of glycosylation in subjects with amino acid substitutions at positions 71 and/or 84 was significantly (P < 0.05) higher than that in subjects with the wild type. 24959350 0 49 theme a4 60:61 arg1 protein 63:69 serum amyloid a4 protein 46:69 serum amyloid a4 protein 46:69 Influence of polymorphism on glycosylation of serum amyloid a4 protein. 24959350 5 50 theme PCR 505:507 arg1 sequencing 525:534 PCR combined direct sequencing 505:534 PCR combined direct sequencing 505:534 In 55 healthy subjects, SAA4 polymorphism was analyzed by PCR combined direct sequencing and its glycosylation status was analyzed by immunoblotting. 24959350 6 51 with subjects 770:777 arg1 type 793:796 the wild type 784:796 the wild type 784:796 The results showed that the percentage of glycosylation in subjects with amino acid substitutions at positions 71 and/or 84 was significantly (P < 0.05) higher than that in subjects with the wild type. 24959350 7 52 theme plasma 840:845 arg1 concentration 847:859 the plasma concentration 836:859 the plasma concentration of SAA4 836:867 The polymorphism had no influence on the plasma concentration of SAA4. 27918560 0 0 from mapping 21:27 arg1 melanogaster 70:81 Drosophila melanogaster 59:81 Drosophila melanogaster 59:81 Genome-wide chemical mapping of O-GlcNAcylated proteins in Drosophila melanogaster. 27918560 1 1 from expression 196:205 arg1 organisms 210:218 organisms 210:218 organisms 210:218 N-Acetylglucosamine β-O-linked to nucleocytoplasmic proteins (O-GlcNAc) is implicated in the regulation of gene expression in organisms, from humans to Drosophila melanogaster. 27918560 1 1 from expression 196:205 arg1 humans 226:231 humans 226:231 humans to Drosophila melanogaster 226:258 N-Acetylglucosamine β-O-linked to nucleocytoplasmic proteins (O-GlcNAc) is implicated in the regulation of gene expression in organisms, from humans to Drosophila melanogaster. 27918560 2 2 theme target 449:454 arg1 genes 456:460 homeotic (HOX) and other PcG target genes 420:460 genes 456:460 Within Drosophila, O-GlcNAc transferase (OGT) is one of the Polycomb group proteins (PcGs) that act through Polycomb group response elements (PREs) to silence homeotic (HOX) and other PcG target genes. 27918560 1 3 from regulation 177:186 arg1 organisms 210:218 organisms 210:218 organisms 210:218 N-Acetylglucosamine β-O-linked to nucleocytoplasmic proteins (O-GlcNAc) is implicated in the regulation of gene expression in organisms, from humans to Drosophila melanogaster. 27918560 5 4 theme gene 886:889 arg1 expression 891:900 altered gene expression 878:900 altered gene expression 878:900 Many of these loci overlap with PREs, but O-GlcNAc is also present at other loci lacking PREs. Loss of OGT leads to altered gene expression not only at loci containing PREs but also at loci lacking PREs, including several heterochromatic genes. 27918560 3 5 theme PcG 512:514 arg1 proteins 516:523 new O-GlcNAcylated PcG proteins 493:523 new O-GlcNAcylated PcG proteins 493:523 Using Drosophila, we identify new O-GlcNAcylated PcG proteins and develop an antibody-free metabolic feeding approach to chemoselectively map genomic loci enriched in O-GlcNAc using next-generation sequencing. 27918560 1 6 link β-O-linked 104:113 arg1 N-Acetylglucosamine 84:102 N-Acetylglucosamine 84:102 N-Acetylglucosamine β-O-linked to nucleocytoplasmic proteins (O-GlcNAc) 84:154 N-Acetylglucosamine β-O-linked to nucleocytoplasmic proteins (O-GlcNAc) is implicated in the regulation of gene expression in organisms, from humans to Drosophila melanogaster. 27918560 1 6 link β-O-linked 104:113 arg1 O-GlcNAc 146:153 O-GlcNAc 146:153 O-GlcNAc 146:153 N-Acetylglucosamine β-O-linked to nucleocytoplasmic proteins (O-GlcNAc) is implicated in the regulation of gene expression in organisms, from humans to Drosophila melanogaster. 27918560 4 7 theme specific 713:720 arg1 loci 730:733 specific genomic loci 713:733 specific genomic loci 713:733 We find that O-GlcNAc is distributed to specific genomic loci both in cells and in vivo. 27918560 6 8 theme gene 1085:1088 arg1 expression 1090:1099 gene expression 1085:1099 gene expression in Drosophila 1085:1113 These data suggest that O-GlcNAc acts through multiple mechanisms to regulate gene expression in Drosophila. 27918560 3 9 theme new 493:495 arg1 proteins 516:523 new O-GlcNAcylated PcG proteins 493:523 new O-GlcNAcylated PcG proteins 493:523 Using Drosophila, we identify new O-GlcNAcylated PcG proteins and develop an antibody-free metabolic feeding approach to chemoselectively map genomic loci enriched in O-GlcNAc using next-generation sequencing. 27918560 5 10 contain containing 919:928 arg2 PREs 930:933 PREs 930:933 PREs 930:933 Many of these loci overlap with PREs, but O-GlcNAc is also present at other loci lacking PREs. Loss of OGT leads to altered gene expression not only at loci containing PREs but also at loci lacking PREs, including several heterochromatic genes. 27918560 5 10 contain containing 919:928 arg1 loci 914:917 loci 914:917 loci containing PREs 914:933 Many of these loci overlap with PREs, but O-GlcNAc is also present at other loci lacking PREs. Loss of OGT leads to altered gene expression not only at loci containing PREs but also at loci lacking PREs, including several heterochromatic genes. 27918560 1 11 theme gene 191:194 arg1 expression 196:205 gene expression 191:205 gene expression in organisms, from humans to Drosophila melanogaster 191:258 N-Acetylglucosamine β-O-linked to nucleocytoplasmic proteins (O-GlcNAc) is implicated in the regulation of gene expression in organisms, from humans to Drosophila melanogaster. 27918560 5 12 theme loci 776:779 arg1 Many 762:765 Many 762:765 Many 762:765 Many of these loci overlap with PREs, but O-GlcNAc is also present at other loci lacking PREs. Loss of OGT leads to altered gene expression not only at loci containing PREs but also at loci lacking PREs, including several heterochromatic genes. 27918560 5 12 theme loci 776:779 arg1 loci 776:779 these loci 770:779 these loci 770:779 Many of these loci overlap with PREs, but O-GlcNAc is also present at other loci lacking PREs. Loss of OGT leads to altered gene expression not only at loci containing PREs but also at loci lacking PREs, including several heterochromatic genes. 27918560 0 13 theme proteins 47:54 arg1 mapping 21:27 Genome-wide chemical mapping 0:27 Genome-wide chemical mapping of O-GlcNAcylated proteins in Drosophila melanogaster. 0:82 Genome-wide chemical mapping of O-GlcNAcylated proteins in Drosophila melanogaster. 27918560 1 14 theme β-O-linked 104:113 arg1 N-Acetylglucosamine 84:102 N-Acetylglucosamine 84:102 N-Acetylglucosamine β-O-linked to nucleocytoplasmic proteins (O-GlcNAc) 84:154 N-Acetylglucosamine β-O-linked to nucleocytoplasmic proteins (O-GlcNAc) is implicated in the regulation of gene expression in organisms, from humans to Drosophila melanogaster. 27918560 1 14 theme β-O-linked 104:113 arg1 O-GlcNAc 146:153 O-GlcNAc 146:153 O-GlcNAc 146:153 N-Acetylglucosamine β-O-linked to nucleocytoplasmic proteins (O-GlcNAc) is implicated in the regulation of gene expression in organisms, from humans to Drosophila melanogaster. 27918560 1 15 theme expression 196:205 arg1 regulation 177:186 the regulation 173:186 the regulation of gene expression in organisms, from humans to Drosophila melanogaster 173:258 N-Acetylglucosamine β-O-linked to nucleocytoplasmic proteins (O-GlcNAc) is implicated in the regulation of gene expression in organisms, from humans to Drosophila melanogaster. 27918560 0 16 theme chemical 12:19 arg1 mapping 21:27 Genome-wide chemical mapping 0:27 Genome-wide chemical mapping of O-GlcNAcylated proteins in Drosophila melanogaster. 0:82 Genome-wide chemical mapping of O-GlcNAcylated proteins in Drosophila melanogaster. 27918560 2 17 theme Polycomb 321:328 arg1 PcGs 346:349 PcGs 346:349 PcGs 346:349 Within Drosophila, O-GlcNAc transferase (OGT) is one of the Polycomb group proteins (PcGs) that act through Polycomb group response elements (PREs) to silence homeotic (HOX) and other PcG target genes. 27918560 2 17 theme Polycomb 321:328 arg1 proteins 336:343 the Polycomb group proteins 317:343 the Polycomb group proteins (PcGs) that act through Polycomb group response elements (PREs) to silence homeotic (HOX) and other PcG target genes 317:460 Within Drosophila, O-GlcNAc transferase (OGT) is one of the Polycomb group proteins (PcGs) that act through Polycomb group response elements (PREs) to silence homeotic (HOX) and other PcG target genes. 27918560 2 18 theme group 378:382 arg1 PREs 403:406 PREs 403:406 PREs 403:406 Within Drosophila, O-GlcNAc transferase (OGT) is one of the Polycomb group proteins (PcGs) that act through Polycomb group response elements (PREs) to silence homeotic (HOX) and other PcG target genes. 27918560 2 18 theme group 378:382 arg1 elements 393:400 Polycomb group response elements 369:400 Polycomb group response elements (PREs) 369:407 Within Drosophila, O-GlcNAc transferase (OGT) is one of the Polycomb group proteins (PcGs) that act through Polycomb group response elements (PREs) to silence homeotic (HOX) and other PcG target genes. 27918560 0 19 theme Genome-wide 0:10 arg1 mapping 21:27 Genome-wide chemical mapping 0:27 Genome-wide chemical mapping of O-GlcNAcylated proteins in Drosophila melanogaster. 0:82 Genome-wide chemical mapping of O-GlcNAcylated proteins in Drosophila melanogaster. 27918560 1 20 theme nucleocytoplasmic 118:134 arg1 proteins 136:143 nucleocytoplasmic proteins 118:143 nucleocytoplasmic proteins 118:143 N-Acetylglucosamine β-O-linked to nucleocytoplasmic proteins (O-GlcNAc) is implicated in the regulation of gene expression in organisms, from humans to Drosophila melanogaster. 27918560 2 21 theme Polycomb 369:376 arg1 PREs 403:406 PREs 403:406 PREs 403:406 Within Drosophila, O-GlcNAc transferase (OGT) is one of the Polycomb group proteins (PcGs) that act through Polycomb group response elements (PREs) to silence homeotic (HOX) and other PcG target genes. 27918560 2 21 theme Polycomb 369:376 arg1 elements 393:400 Polycomb group response elements 369:400 Polycomb group response elements (PREs) 369:407 Within Drosophila, O-GlcNAc transferase (OGT) is one of the Polycomb group proteins (PcGs) that act through Polycomb group response elements (PREs) to silence homeotic (HOX) and other PcG target genes. 27918560 2 22 theme homeotic 420:427 arg1 HOX 430:432 homeotic (HOX) and other PcG target genes 420:460 HOX 430:432 Within Drosophila, O-GlcNAc transferase (OGT) is one of the Polycomb group proteins (PcGs) that act through Polycomb group response elements (PREs) to silence homeotic (HOX) and other PcG target genes. 27918560 5 23 theme altered 878:884 arg1 expression 891:900 altered gene expression 878:900 altered gene expression 878:900 Many of these loci overlap with PREs, but O-GlcNAc is also present at other loci lacking PREs. Loss of OGT leads to altered gene expression not only at loci containing PREs but also at loci lacking PREs, including several heterochromatic genes. 27918560 6 24 from expression 1090:1099 arg1 Drosophila 1104:1113 Drosophila 1104:1113 Drosophila 1104:1113 These data suggest that O-GlcNAc acts through multiple mechanisms to regulate gene expression in Drosophila. 27918560 3 25 theme antibody-free 540:552 arg1 approach 572:579 an antibody-free metabolic feeding approach 537:579 an antibody-free metabolic feeding approach to chemoselectively map genomic loci enriched in O-GlcNAc using next-generation sequencing 537:670 Using Drosophila, we identify new O-GlcNAcylated PcG proteins and develop an antibody-free metabolic feeding approach to chemoselectively map genomic loci enriched in O-GlcNAc using next-generation sequencing. 27918560 5 26 dep PREs. 851:855 arg1 leads 869:873 leads 869:873 leads to altered gene expression not only at loci containing PREs but also at loci lacking PREs, including several heterochromatic genes 869:1004 Many of these loci overlap with PREs, but O-GlcNAc is also present at other loci lacking PREs. Loss of OGT leads to altered gene expression not only at loci containing PREs but also at loci lacking PREs, including several heterochromatic genes. 27918560 2 27 theme PcG 445:447 arg1 genes 456:460 homeotic (HOX) and other PcG target genes 420:460 genes 456:460 Within Drosophila, O-GlcNAc transferase (OGT) is one of the Polycomb group proteins (PcGs) that act through Polycomb group response elements (PREs) to silence homeotic (HOX) and other PcG target genes. 27918560 5 28 attach present 821:827 arg2 O-GlcNAc 804:811 O-GlcNAc 804:811 O-GlcNAc 804:811 Many of these loci overlap with PREs, but O-GlcNAc is also present at other loci lacking PREs. Loss of OGT leads to altered gene expression not only at loci containing PREs but also at loci lacking PREs, including several heterochromatic genes. 27918560 5 28 attach present 821:827 arg1 loci 838:841 other loci 832:841 other loci lacking PREs. Loss of OGT leads to altered gene expression not only at loci containing PREs but also at loci lacking PREs, including several heterochromatic genes 832:1004 Many of these loci overlap with PREs, but O-GlcNAc is also present at other loci lacking PREs. Loss of OGT leads to altered gene expression not only at loci containing PREs but also at loci lacking PREs, including several heterochromatic genes. 27918560 0 29 theme O-GlcNAcylated 32:45 arg1 proteins 47:54 O-GlcNAcylated proteins 32:54 O-GlcNAcylated proteins 32:54 Genome-wide chemical mapping of O-GlcNAcylated proteins in Drosophila melanogaster. 27918560 2 30 theme other 439:443 arg1 genes 456:460 homeotic (HOX) and other PcG target genes 420:460 genes 456:460 Within Drosophila, O-GlcNAc transferase (OGT) is one of the Polycomb group proteins (PcGs) that act through Polycomb group response elements (PREs) to silence homeotic (HOX) and other PcG target genes. 27918560 1 31 from humans 226:231 arg1 organisms 210:218 organisms 210:218 organisms 210:218 N-Acetylglucosamine β-O-linked to nucleocytoplasmic proteins (O-GlcNAc) is implicated in the regulation of gene expression in organisms, from humans to Drosophila melanogaster. 27918560 1 31 from humans 226:231 arg1 expression 196:205 gene expression 191:205 gene expression in organisms, from humans to Drosophila melanogaster 191:258 N-Acetylglucosamine β-O-linked to nucleocytoplasmic proteins (O-GlcNAc) is implicated in the regulation of gene expression in organisms, from humans to Drosophila melanogaster. 27918560 5 32 theme other 832:836 arg1 loci 838:841 other loci 832:841 other loci lacking PREs. Loss of OGT leads to altered gene expression not only at loci containing PREs but also at loci lacking PREs, including several heterochromatic genes 832:1004 Many of these loci overlap with PREs, but O-GlcNAc is also present at other loci lacking PREs. Loss of OGT leads to altered gene expression not only at loci containing PREs but also at loci lacking PREs, including several heterochromatic genes. 27918560 5 33 from loci 838:841 arg1 present 821:827 present 821:827 present 821:827 Many of these loci overlap with PREs, but O-GlcNAc is also present at other loci lacking PREs. Loss of OGT leads to altered gene expression not only at loci containing PREs but also at loci lacking PREs, including several heterochromatic genes. 27918560 3 34 theme metabolic 554:562 arg1 approach 572:579 an antibody-free metabolic feeding approach 537:579 an antibody-free metabolic feeding approach to chemoselectively map genomic loci enriched in O-GlcNAc using next-generation sequencing 537:670 Using Drosophila, we identify new O-GlcNAcylated PcG proteins and develop an antibody-free metabolic feeding approach to chemoselectively map genomic loci enriched in O-GlcNAc using next-generation sequencing. 27918560 5 35 theme OGT 865:867 arg1 Loss 857:860 Loss 857:860 Loss of OGT 857:867 Many of these loci overlap with PREs, but O-GlcNAc is also present at other loci lacking PREs. Loss of OGT leads to altered gene expression not only at loci containing PREs but also at loci lacking PREs, including several heterochromatic genes. 27918560 5 36 located present 821:827 arg2 O-GlcNAc 804:811 O-GlcNAc 804:811 O-GlcNAc 804:811 Many of these loci overlap with PREs, but O-GlcNAc is also present at other loci lacking PREs. Loss of OGT leads to altered gene expression not only at loci containing PREs but also at loci lacking PREs, including several heterochromatic genes. 27918560 5 36 located present 821:827 arg1 loci 838:841 other loci 832:841 other loci lacking PREs. Loss of OGT leads to altered gene expression not only at loci containing PREs but also at loci lacking PREs, including several heterochromatic genes 832:1004 Many of these loci overlap with PREs, but O-GlcNAc is also present at other loci lacking PREs. Loss of OGT leads to altered gene expression not only at loci containing PREs but also at loci lacking PREs, including several heterochromatic genes. 27918560 5 37 theme several 976:982 arg1 genes 1000:1004 several heterochromatic genes 976:1004 several heterochromatic genes 976:1004 Many of these loci overlap with PREs, but O-GlcNAc is also present at other loci lacking PREs. Loss of OGT leads to altered gene expression not only at loci containing PREs but also at loci lacking PREs, including several heterochromatic genes. 27918560 3 38 theme feeding 564:570 arg1 approach 572:579 an antibody-free metabolic feeding approach 537:579 an antibody-free metabolic feeding approach to chemoselectively map genomic loci enriched in O-GlcNAc using next-generation sequencing 537:670 Using Drosophila, we identify new O-GlcNAcylated PcG proteins and develop an antibody-free metabolic feeding approach to chemoselectively map genomic loci enriched in O-GlcNAc using next-generation sequencing. 27918560 5 39 theme heterochromatic 984:998 arg1 genes 1000:1004 several heterochromatic genes 976:1004 several heterochromatic genes 976:1004 Many of these loci overlap with PREs, but O-GlcNAc is also present at other loci lacking PREs. Loss of OGT leads to altered gene expression not only at loci containing PREs but also at loci lacking PREs, including several heterochromatic genes. 27918560 3 40 theme genomic 605:611 arg1 loci 613:616 map genomic loci 601:616 map genomic loci enriched in O-GlcNAc using next-generation sequencing 601:670 Using Drosophila, we identify new O-GlcNAcylated PcG proteins and develop an antibody-free metabolic feeding approach to chemoselectively map genomic loci enriched in O-GlcNAc using next-generation sequencing. 27918560 2 41 theme proteins 336:343 arg1 PcGs 346:349 PcGs 346:349 PcGs 346:349 Within Drosophila, O-GlcNAc transferase (OGT) is one of the Polycomb group proteins (PcGs) that act through Polycomb group response elements (PREs) to silence homeotic (HOX) and other PcG target genes. 27918560 2 41 theme proteins 336:343 arg1 proteins 336:343 the Polycomb group proteins 317:343 the Polycomb group proteins (PcGs) that act through Polycomb group response elements (PREs) to silence homeotic (HOX) and other PcG target genes 317:460 Within Drosophila, O-GlcNAc transferase (OGT) is one of the Polycomb group proteins (PcGs) that act through Polycomb group response elements (PREs) to silence homeotic (HOX) and other PcG target genes. 27918560 2 41 theme proteins 336:343 arg1 one 310:312 one 310:312 one 310:312 Within Drosophila, O-GlcNAc transferase (OGT) is one of the Polycomb group proteins (PcGs) that act through Polycomb group response elements (PREs) to silence homeotic (HOX) and other PcG target genes. 27918560 3 42 theme O-GlcNAcylated 497:510 arg1 proteins 516:523 new O-GlcNAcylated PcG proteins 493:523 new O-GlcNAcylated PcG proteins 493:523 Using Drosophila, we identify new O-GlcNAcylated PcG proteins and develop an antibody-free metabolic feeding approach to chemoselectively map genomic loci enriched in O-GlcNAc using next-generation sequencing. 27918560 3 43 theme next-generation 645:659 arg1 sequencing 661:670 next-generation sequencing 645:670 next-generation sequencing 645:670 Using Drosophila, we identify new O-GlcNAcylated PcG proteins and develop an antibody-free metabolic feeding approach to chemoselectively map genomic loci enriched in O-GlcNAc using next-generation sequencing. 27918560 2 44 theme O-GlcNAc 280:287 arg1 OGT 302:304 OGT 302:304 OGT 302:304 Within Drosophila, O-GlcNAc transferase (OGT) is one of the Polycomb group proteins (PcGs) that act through Polycomb group response elements (PREs) to silence homeotic (HOX) and other PcG target genes. 27918560 2 44 theme O-GlcNAc 280:287 arg1 transferase 289:299 O-GlcNAc transferase 280:299 O-GlcNAc transferase (OGT) 280:305 Within Drosophila, O-GlcNAc transferase (OGT) is one of the Polycomb group proteins (PcGs) that act through Polycomb group response elements (PREs) to silence homeotic (HOX) and other PcG target genes. 27918560 2 45 theme group 330:334 arg1 PcGs 346:349 PcGs 346:349 PcGs 346:349 Within Drosophila, O-GlcNAc transferase (OGT) is one of the Polycomb group proteins (PcGs) that act through Polycomb group response elements (PREs) to silence homeotic (HOX) and other PcG target genes. 27918560 2 45 theme group 330:334 arg1 proteins 336:343 the Polycomb group proteins 317:343 the Polycomb group proteins (PcGs) that act through Polycomb group response elements (PREs) to silence homeotic (HOX) and other PcG target genes 317:460 Within Drosophila, O-GlcNAc transferase (OGT) is one of the Polycomb group proteins (PcGs) that act through Polycomb group response elements (PREs) to silence homeotic (HOX) and other PcG target genes. 27918560 4 46 theme genomic 722:728 arg1 loci 730:733 specific genomic loci 713:733 specific genomic loci 713:733 We find that O-GlcNAc is distributed to specific genomic loci both in cells and in vivo. 27918560 1 47 from organisms 210:218 arg1 regulation 177:186 the regulation 173:186 the regulation of gene expression in organisms, from humans to Drosophila melanogaster 173:258 N-Acetylglucosamine β-O-linked to nucleocytoplasmic proteins (O-GlcNAc) is implicated in the regulation of gene expression in organisms, from humans to Drosophila melanogaster. 27918560 6 48 theme multiple 1053:1060 arg1 mechanisms 1062:1071 multiple mechanisms 1053:1071 multiple mechanisms 1053:1071 These data suggest that O-GlcNAc acts through multiple mechanisms to regulate gene expression in Drosophila. 27918560 2 49 theme response 384:391 arg1 PREs 403:406 PREs 403:406 PREs 403:406 Within Drosophila, O-GlcNAc transferase (OGT) is one of the Polycomb group proteins (PcGs) that act through Polycomb group response elements (PREs) to silence homeotic (HOX) and other PcG target genes. 27918560 2 49 theme response 384:391 arg1 elements 393:400 Polycomb group response elements 369:400 Polycomb group response elements (PREs) 369:407 Within Drosophila, O-GlcNAc transferase (OGT) is one of the Polycomb group proteins (PcGs) that act through Polycomb group response elements (PREs) to silence homeotic (HOX) and other PcG target genes. 27918560 3 50 theme map 601:603 arg1 loci 613:616 map genomic loci 601:616 map genomic loci enriched in O-GlcNAc using next-generation sequencing 601:670 Using Drosophila, we identify new O-GlcNAcylated PcG proteins and develop an antibody-free metabolic feeding approach to chemoselectively map genomic loci enriched in O-GlcNAc using next-generation sequencing. 27255611 5 0 theme protein 779:785 arg1 modifications 787:799 O-linked β-N-acetylglucosamine protein modifications 748:799 O-linked β-N-acetylglucosamine protein modifications 748:799 The increased production of GFAT1 stimulates HBP flux and results in an increase in O-linked β-N-acetylglucosamine protein modifications. 27255611 1 1 theme nutrient-sensing 148:163 arg1 pathway 175:181 a nutrient-sensing metabolic pathway 146:181 a nutrient-sensing metabolic pathway that produces the activated amino sugar UDP-N-acetylglucosamine, a critical substrate for protein glycosylation 146:293 The hexosamine biosynthetic pathway (HBP) is a nutrient-sensing metabolic pathway that produces the activated amino sugar UDP-N-acetylglucosamine, a critical substrate for protein glycosylation. 27255611 1 1 theme nutrient-sensing 148:163 arg1 pathway 129:135 The hexosamine biosynthetic pathway 101:135 The hexosamine biosynthetic pathway (HBP) 101:141 The hexosamine biosynthetic pathway (HBP) is a nutrient-sensing metabolic pathway that produces the activated amino sugar UDP-N-acetylglucosamine, a critical substrate for protein glycosylation. 27255611 4 2 theme transcription 588:600 arg1 factor 602:607 the activating transcription factor 4 573:609 the activating transcription factor 4 (ATF4) induced by the GCN2-eIF2α signalling pathway 573:661 GFAT1 is a transcriptional target of the activating transcription factor 4 (ATF4) induced by the GCN2-eIF2α signalling pathway. 27255611 4 2 theme transcription 588:600 arg1 ATF4 612:615 ATF4 612:615 ATF4 612:615 GFAT1 is a transcriptional target of the activating transcription factor 4 (ATF4) induced by the GCN2-eIF2α signalling pathway. 27255611 0 3 theme signalling 81:90 arg1 pathway 92:98 the GCN2-ATF4 signalling pathway 67:98 the GCN2-ATF4 signalling pathway 67:98 Nutrient shortage triggers the hexosamine biosynthetic pathway via the GCN2-ATF4 signalling pathway. 27255611 1 4 theme metabolic 165:173 arg1 pathway 175:181 a nutrient-sensing metabolic pathway 146:181 a nutrient-sensing metabolic pathway that produces the activated amino sugar UDP-N-acetylglucosamine, a critical substrate for protein glycosylation 146:293 The hexosamine biosynthetic pathway (HBP) is a nutrient-sensing metabolic pathway that produces the activated amino sugar UDP-N-acetylglucosamine, a critical substrate for protein glycosylation. 27255611 1 4 theme metabolic 165:173 arg1 pathway 129:135 The hexosamine biosynthetic pathway 101:135 The hexosamine biosynthetic pathway (HBP) 101:141 The hexosamine biosynthetic pathway (HBP) is a nutrient-sensing metabolic pathway that produces the activated amino sugar UDP-N-acetylglucosamine, a critical substrate for protein glycosylation. 27255611 1 5 theme protein 273:279 arg1 glycosylation 281:293 protein glycosylation 273:293 protein glycosylation 273:293 The hexosamine biosynthetic pathway (HBP) is a nutrient-sensing metabolic pathway that produces the activated amino sugar UDP-N-acetylglucosamine, a critical substrate for protein glycosylation. 27255611 2 6 theme HBP 373:375 arg1 flux 377:380 HBP flux 373:380 HBP flux 373:380 Despite its biological significance, little is known about the regulation of HBP flux during nutrient limitation. 27255611 5 7 theme increased 668:676 arg1 production 678:687 The increased production 664:687 The increased production of GFAT1 664:696 The increased production of GFAT1 stimulates HBP flux and results in an increase in O-linked β-N-acetylglucosamine protein modifications. 27255611 2 8 theme biological 308:317 arg1 significance 319:330 its biological significance 304:330 its biological significance 304:330 Despite its biological significance, little is known about the regulation of HBP flux during nutrient limitation. 27255611 4 9 theme factor 602:607 arg1 target 563:568 a transcriptional target 545:568 a transcriptional target of the activating transcription factor 4 (ATF4) induced by the GCN2-eIF2α signalling pathway 545:661 GFAT1 is a transcriptional target of the activating transcription factor 4 (ATF4) induced by the GCN2-eIF2α signalling pathway. 27255611 4 9 theme factor 602:607 arg1 GFAT1 536:540 GFAT1 536:540 GFAT1 536:540 GFAT1 is a transcriptional target of the activating transcription factor 4 (ATF4) induced by the GCN2-eIF2α signalling pathway. 27255611 3 10 theme glucose 445:451 arg1 shortage 453:460 glucose shortage 445:460 glucose shortage 445:460 Here, we report that amino acid or glucose shortage increase GFAT1 production, the first and rate-limiting enzyme of the HBP. 27255611 5 11 theme O-linked 748:755 arg1 modifications 787:799 O-linked β-N-acetylglucosamine protein modifications 748:799 O-linked β-N-acetylglucosamine protein modifications 748:799 The increased production of GFAT1 stimulates HBP flux and results in an increase in O-linked β-N-acetylglucosamine protein modifications. 27255611 0 12 theme Nutrient 0:7 arg1 shortage 9:16 Nutrient shortage 0:16 Nutrient shortage 0:16 Nutrient shortage triggers the hexosamine biosynthetic pathway via the GCN2-ATF4 signalling pathway. 27255611 4 13 theme transcriptional 547:561 arg1 target 563:568 a transcriptional target 545:568 a transcriptional target of the activating transcription factor 4 (ATF4) induced by the GCN2-eIF2α signalling pathway 545:661 GFAT1 is a transcriptional target of the activating transcription factor 4 (ATF4) induced by the GCN2-eIF2α signalling pathway. 27255611 4 13 theme transcriptional 547:561 arg1 GFAT1 536:540 GFAT1 536:540 GFAT1 536:540 GFAT1 is a transcriptional target of the activating transcription factor 4 (ATF4) induced by the GCN2-eIF2α signalling pathway. 27255611 5 14 theme HBP 709:711 arg1 flux 713:716 HBP flux 709:716 HBP flux 709:716 The increased production of GFAT1 stimulates HBP flux and results in an increase in O-linked β-N-acetylglucosamine protein modifications. 27255611 1 15 theme hexosamine 105:114 arg1 HBP 138:140 HBP 138:140 HBP 138:140 The hexosamine biosynthetic pathway (HBP) is a nutrient-sensing metabolic pathway that produces the activated amino sugar UDP-N-acetylglucosamine, a critical substrate for protein glycosylation. 27255611 1 15 theme hexosamine 105:114 arg1 pathway 129:135 The hexosamine biosynthetic pathway 101:135 The hexosamine biosynthetic pathway (HBP) 101:141 The hexosamine biosynthetic pathway (HBP) is a nutrient-sensing metabolic pathway that produces the activated amino sugar UDP-N-acetylglucosamine, a critical substrate for protein glycosylation. 27255611 1 15 theme hexosamine 105:114 arg1 pathway 175:181 a nutrient-sensing metabolic pathway 146:181 a nutrient-sensing metabolic pathway that produces the activated amino sugar UDP-N-acetylglucosamine, a critical substrate for protein glycosylation 146:293 The hexosamine biosynthetic pathway (HBP) is a nutrient-sensing metabolic pathway that produces the activated amino sugar UDP-N-acetylglucosamine, a critical substrate for protein glycosylation. 27255611 1 16 theme activated 201:209 arg1 substrate 259:267 a critical substrate 248:267 a critical substrate for protein glycosylation 248:293 The hexosamine biosynthetic pathway (HBP) is a nutrient-sensing metabolic pathway that produces the activated amino sugar UDP-N-acetylglucosamine, a critical substrate for protein glycosylation. 27255611 1 16 theme activated 201:209 arg1 UDP-N-acetylglucosamine 223:245 the activated amino sugar UDP-N-acetylglucosamine 197:245 the activated amino sugar UDP-N-acetylglucosamine 197:245 The hexosamine biosynthetic pathway (HBP) is a nutrient-sensing metabolic pathway that produces the activated amino sugar UDP-N-acetylglucosamine, a critical substrate for protein glycosylation. 27255611 5 17 from increase 736:743 arg1 modifications 787:799 O-linked β-N-acetylglucosamine protein modifications 748:799 O-linked β-N-acetylglucosamine protein modifications 748:799 The increased production of GFAT1 stimulates HBP flux and results in an increase in O-linked β-N-acetylglucosamine protein modifications. 27255611 1 18 theme biosynthetic 116:127 arg1 HBP 138:140 HBP 138:140 HBP 138:140 The hexosamine biosynthetic pathway (HBP) is a nutrient-sensing metabolic pathway that produces the activated amino sugar UDP-N-acetylglucosamine, a critical substrate for protein glycosylation. 27255611 1 18 theme biosynthetic 116:127 arg1 pathway 129:135 The hexosamine biosynthetic pathway 101:135 The hexosamine biosynthetic pathway (HBP) 101:141 The hexosamine biosynthetic pathway (HBP) is a nutrient-sensing metabolic pathway that produces the activated amino sugar UDP-N-acetylglucosamine, a critical substrate for protein glycosylation. 27255611 1 18 theme biosynthetic 116:127 arg1 pathway 175:181 a nutrient-sensing metabolic pathway 146:181 a nutrient-sensing metabolic pathway that produces the activated amino sugar UDP-N-acetylglucosamine, a critical substrate for protein glycosylation 146:293 The hexosamine biosynthetic pathway (HBP) is a nutrient-sensing metabolic pathway that produces the activated amino sugar UDP-N-acetylglucosamine, a critical substrate for protein glycosylation. 27255611 4 19 theme activating 577:586 arg1 factor 602:607 the activating transcription factor 4 573:609 the activating transcription factor 4 (ATF4) induced by the GCN2-eIF2α signalling pathway 573:661 GFAT1 is a transcriptional target of the activating transcription factor 4 (ATF4) induced by the GCN2-eIF2α signalling pathway. 27255611 4 19 theme activating 577:586 arg1 ATF4 612:615 ATF4 612:615 ATF4 612:615 GFAT1 is a transcriptional target of the activating transcription factor 4 (ATF4) induced by the GCN2-eIF2α signalling pathway. 27255611 1 20 theme amino 211:215 arg1 substrate 259:267 a critical substrate 248:267 a critical substrate for protein glycosylation 248:293 The hexosamine biosynthetic pathway (HBP) is a nutrient-sensing metabolic pathway that produces the activated amino sugar UDP-N-acetylglucosamine, a critical substrate for protein glycosylation. 27255611 1 20 theme amino 211:215 arg1 UDP-N-acetylglucosamine 223:245 the activated amino sugar UDP-N-acetylglucosamine 197:245 the activated amino sugar UDP-N-acetylglucosamine 197:245 The hexosamine biosynthetic pathway (HBP) is a nutrient-sensing metabolic pathway that produces the activated amino sugar UDP-N-acetylglucosamine, a critical substrate for protein glycosylation. 27255611 0 21 theme biosynthetic 42:53 arg1 pathway 55:61 the hexosamine biosynthetic pathway 27:61 the hexosamine biosynthetic pathway 27:61 Nutrient shortage triggers the hexosamine biosynthetic pathway via the GCN2-ATF4 signalling pathway. 27255611 4 22 theme signalling 644:653 arg1 pathway 655:661 the GCN2-eIF2α signalling pathway 629:661 the GCN2-eIF2α signalling pathway 629:661 GFAT1 is a transcriptional target of the activating transcription factor 4 (ATF4) induced by the GCN2-eIF2α signalling pathway. 27255611 1 23 theme sugar 217:221 arg1 substrate 259:267 a critical substrate 248:267 a critical substrate for protein glycosylation 248:293 The hexosamine biosynthetic pathway (HBP) is a nutrient-sensing metabolic pathway that produces the activated amino sugar UDP-N-acetylglucosamine, a critical substrate for protein glycosylation. 27255611 1 23 theme sugar 217:221 arg1 UDP-N-acetylglucosamine 223:245 the activated amino sugar UDP-N-acetylglucosamine 197:245 the activated amino sugar UDP-N-acetylglucosamine 197:245 The hexosamine biosynthetic pathway (HBP) is a nutrient-sensing metabolic pathway that produces the activated amino sugar UDP-N-acetylglucosamine, a critical substrate for protein glycosylation. 27255611 0 24 theme hexosamine 31:40 arg1 pathway 55:61 the hexosamine biosynthetic pathway 27:61 the hexosamine biosynthetic pathway 27:61 Nutrient shortage triggers the hexosamine biosynthetic pathway via the GCN2-ATF4 signalling pathway. 27255611 2 25 theme flux 377:380 arg1 regulation 359:368 the regulation 355:368 the regulation of HBP flux during nutrient limitation 355:407 Despite its biological significance, little is known about the regulation of HBP flux during nutrient limitation. 27255611 3 26 theme amino 431:435 arg1 acid 437:440 amino acid 431:440 amino acid 431:440 Here, we report that amino acid or glucose shortage increase GFAT1 production, the first and rate-limiting enzyme of the HBP. 27255611 6 27 theme nutritional 879:889 arg1 stress 891:896 nutritional stress 879:896 nutritional stress 879:896 Taken together, these findings demonstrate that ATF4 provides a link between nutritional stress and the HBP for the regulation of the O-GlcNAcylation-dependent cellular signalling. 27255611 3 28 theme GFAT1 471:475 arg1 production 477:486 GFAT1 production 471:486 GFAT1 production 471:486 Here, we report that amino acid or glucose shortage increase GFAT1 production, the first and rate-limiting enzyme of the HBP. 27255611 3 28 theme GFAT1 471:475 arg1 enzyme 517:522 the first and rate-limiting enzyme 489:522 the first and rate-limiting enzyme of the HBP 489:533 Here, we report that amino acid or glucose shortage increase GFAT1 production, the first and rate-limiting enzyme of the HBP. 27255611 6 29 theme signalling 971:980 arg1 regulation 918:927 the regulation 914:927 the regulation of the O-GlcNAcylation-dependent cellular signalling 914:980 Taken together, these findings demonstrate that ATF4 provides a link between nutritional stress and the HBP for the regulation of the O-GlcNAcylation-dependent cellular signalling. 27255611 3 30 theme rate-limiting 503:515 arg1 production 477:486 GFAT1 production 471:486 GFAT1 production 471:486 Here, we report that amino acid or glucose shortage increase GFAT1 production, the first and rate-limiting enzyme of the HBP. 27255611 3 30 theme rate-limiting 503:515 arg1 enzyme 517:522 the first and rate-limiting enzyme 489:522 the first and rate-limiting enzyme of the HBP 489:533 Here, we report that amino acid or glucose shortage increase GFAT1 production, the first and rate-limiting enzyme of the HBP. 27255611 6 31 theme cellular 962:969 arg1 signalling 971:980 the O-GlcNAcylation-dependent cellular signalling 932:980 the O-GlcNAcylation-dependent cellular signalling 932:980 Taken together, these findings demonstrate that ATF4 provides a link between nutritional stress and the HBP for the regulation of the O-GlcNAcylation-dependent cellular signalling. 27255611 5 32 theme GFAT1 692:696 arg1 production 678:687 The increased production 664:687 The increased production of GFAT1 664:696 The increased production of GFAT1 stimulates HBP flux and results in an increase in O-linked β-N-acetylglucosamine protein modifications. 27255611 5 33 link O-linked 748:755 arg1 modifications 787:799 O-linked β-N-acetylglucosamine protein modifications 748:799 O-linked β-N-acetylglucosamine protein modifications 748:799 The increased production of GFAT1 stimulates HBP flux and results in an increase in O-linked β-N-acetylglucosamine protein modifications. 27255611 3 34 theme first 493:497 arg1 production 477:486 GFAT1 production 471:486 GFAT1 production 471:486 Here, we report that amino acid or glucose shortage increase GFAT1 production, the first and rate-limiting enzyme of the HBP. 27255611 3 34 theme first 493:497 arg1 enzyme 517:522 the first and rate-limiting enzyme 489:522 the first and rate-limiting enzyme of the HBP 489:533 Here, we report that amino acid or glucose shortage increase GFAT1 production, the first and rate-limiting enzyme of the HBP. 27255611 0 35 theme GCN2-ATF4 71:79 arg1 pathway 92:98 the GCN2-ATF4 signalling pathway 67:98 the GCN2-ATF4 signalling pathway 67:98 Nutrient shortage triggers the hexosamine biosynthetic pathway via the GCN2-ATF4 signalling pathway. 27255611 4 36 theme GCN2-eIF2α 633:642 arg1 pathway 655:661 the GCN2-eIF2α signalling pathway 629:661 the GCN2-eIF2α signalling pathway 629:661 GFAT1 is a transcriptional target of the activating transcription factor 4 (ATF4) induced by the GCN2-eIF2α signalling pathway. 27255611 2 37 theme nutrient 389:396 arg1 limitation 398:407 nutrient limitation 389:407 nutrient limitation 389:407 Despite its biological significance, little is known about the regulation of HBP flux during nutrient limitation. 27255611 1 38 theme critical 250:257 arg1 substrate 259:267 a critical substrate 248:267 a critical substrate for protein glycosylation 248:293 The hexosamine biosynthetic pathway (HBP) is a nutrient-sensing metabolic pathway that produces the activated amino sugar UDP-N-acetylglucosamine, a critical substrate for protein glycosylation. 27255611 1 38 theme critical 250:257 arg1 UDP-N-acetylglucosamine 223:245 the activated amino sugar UDP-N-acetylglucosamine 197:245 the activated amino sugar UDP-N-acetylglucosamine 197:245 The hexosamine biosynthetic pathway (HBP) is a nutrient-sensing metabolic pathway that produces the activated amino sugar UDP-N-acetylglucosamine, a critical substrate for protein glycosylation. 27255611 5 39 theme β-N-acetylglucosamine 757:777 arg1 modifications 787:799 O-linked β-N-acetylglucosamine protein modifications 748:799 O-linked β-N-acetylglucosamine protein modifications 748:799 The increased production of GFAT1 stimulates HBP flux and results in an increase in O-linked β-N-acetylglucosamine protein modifications. 27255611 6 40 theme O-GlcNAcylation-dependent 936:960 arg1 signalling 971:980 the O-GlcNAcylation-dependent cellular signalling 932:980 the O-GlcNAcylation-dependent cellular signalling 932:980 Taken together, these findings demonstrate that ATF4 provides a link between nutritional stress and the HBP for the regulation of the O-GlcNAcylation-dependent cellular signalling. 27255611 3 41 theme HBP 531:533 arg1 production 477:486 GFAT1 production 471:486 GFAT1 production 471:486 Here, we report that amino acid or glucose shortage increase GFAT1 production, the first and rate-limiting enzyme of the HBP. 27255611 3 41 theme HBP 531:533 arg1 enzyme 517:522 the first and rate-limiting enzyme 489:522 the first and rate-limiting enzyme of the HBP 489:533 Here, we report that amino acid or glucose shortage increase GFAT1 production, the first and rate-limiting enzyme of the HBP. 25980911 6 0 theme O-GlcNAcome 799:809 arg1 analysis 811:818 O-GlcNAcome analysis 799:818 O-GlcNAcome analysis of biological samples 799:840 This novel enrichment strategy could be used for O-GlcNAcome analysis of biological samples. 25980911 5 1 theme mass 731:734 arg1 spectrometry 736:747 mass spectrometry 731:747 mass spectrometry 731:747 At least 500fmol of O-GlcNAc-modified peptides was selectively isolated from α-crystallin tryptic peptides and detected by mass spectrometry. 25980911 1 2 theme thiol-disulfide 266:280 arg1 exchange 282:289 a thiol-disulfide exchange 264:289 a thiol-disulfide exchange 264:289 We have developed a selective method for the enrichment of O-linked β-N-acetylglucosamine (O-GlcNAc)-modified peptides, which uses a newly synthesized thiol-alkyne and a thiol-disulfide exchange. 25980911 4 3 theme thiol-reactive 551:564 arg1 resin 566:570 thiol-reactive resin 551:570 thiol-reactive resin 551:570 The thiol-modified peptides were enriched with thiol-reactive resin through a thiol-disulfide exchange. 25980911 4 4 theme thiol-modified 508:521 arg1 peptides 523:530 The thiol-modified peptides 504:530 The thiol-modified peptides 504:530 The thiol-modified peptides were enriched with thiol-reactive resin through a thiol-disulfide exchange. 25980911 5 5 theme tryptic 698:704 arg1 peptides 706:713 α-crystallin tryptic peptides 685:713 α-crystallin tryptic peptides 685:713 At least 500fmol of O-GlcNAc-modified peptides was selectively isolated from α-crystallin tryptic peptides and detected by mass spectrometry. 25980911 5 6 theme α-crystallin 685:696 arg1 peptides 706:713 α-crystallin tryptic peptides 685:713 α-crystallin tryptic peptides 685:713 At least 500fmol of O-GlcNAc-modified peptides was selectively isolated from α-crystallin tryptic peptides and detected by mass spectrometry. 25980911 2 7 theme First 292:296 arg1 peptides 317:324 First, O-GlcNAc-modified peptides 292:324 First, O-GlcNAc-modified peptides 292:324 First, O-GlcNAc-modified peptides were enzymatically labeled with an azide-containing GalNAc analog. 25980911 5 8 attach isolated 671:678 arg2 500fmol 617:623 At least 500fmol 608:623 At least 500fmol of O-GlcNAc-modified peptides 608:653 At least 500fmol of O-GlcNAc-modified peptides was selectively isolated from α-crystallin tryptic peptides and detected by mass spectrometry. 25980911 5 8 attach isolated 671:678 arg1 peptides 706:713 α-crystallin tryptic peptides 685:713 α-crystallin tryptic peptides 685:713 At least 500fmol of O-GlcNAc-modified peptides was selectively isolated from α-crystallin tryptic peptides and detected by mass spectrometry. 25980911 5 9 theme O-GlcNAc-modified 628:644 arg1 peptides 646:653 O-GlcNAc-modified peptides 628:653 O-GlcNAc-modified peptides 628:653 At least 500fmol of O-GlcNAc-modified peptides was selectively isolated from α-crystallin tryptic peptides and detected by mass spectrometry. 25980911 1 10 theme -modified 196:204 arg1 peptides 206:213 O-linked β-N-acetylglucosamine (O-GlcNAc)-modified peptides 155:213 O-linked β-N-acetylglucosamine (O-GlcNAc)-modified peptides 155:213 We have developed a selective method for the enrichment of O-linked β-N-acetylglucosamine (O-GlcNAc)-modified peptides, which uses a newly synthesized thiol-alkyne and a thiol-disulfide exchange. 25980911 5 11 theme peptides 646:653 arg1 500fmol 617:623 At least 500fmol 608:623 At least 500fmol of O-GlcNAc-modified peptides 608:653 At least 500fmol of O-GlcNAc-modified peptides was selectively isolated from α-crystallin tryptic peptides and detected by mass spectrometry. 25980911 1 12 theme peptides 206:213 arg1 enrichment 141:150 the enrichment 137:150 the enrichment of O-linked β-N-acetylglucosamine (O-GlcNAc)-modified peptides 137:213 We have developed a selective method for the enrichment of O-linked β-N-acetylglucosamine (O-GlcNAc)-modified peptides, which uses a newly synthesized thiol-alkyne and a thiol-disulfide exchange. 25980911 3 13 theme azide 403:407 arg1 moiety 409:414 the azide moiety 399:414 the azide moiety 399:414 Then, the azide moiety was reacted with thiol-alkyne through a copper(I)-catalyzed azide-alkyne cycloaddition. 25980911 6 14 used used 790:793 arg2 strategy 772:779 This novel enrichment strategy 750:779 This novel enrichment strategy 750:779 This novel enrichment strategy could be used for O-GlcNAcome analysis of biological samples. 25980911 6 15 theme enrichment 761:770 arg1 strategy 772:779 This novel enrichment strategy 750:779 This novel enrichment strategy 750:779 This novel enrichment strategy could be used for O-GlcNAcome analysis of biological samples. 25980911 0 16 theme O-GlcNAc-modified 14:30 arg1 peptides 32:39 O-GlcNAc-modified peptides 14:39 O-GlcNAc-modified peptides 14:39 Enrichment of O-GlcNAc-modified peptides using novel thiol-alkyne and thiol-disulfide exchange. 25980911 1 17 theme selective 116:124 arg1 method 126:131 a selective method 114:131 a selective method 114:131 We have developed a selective method for the enrichment of O-linked β-N-acetylglucosamine (O-GlcNAc)-modified peptides, which uses a newly synthesized thiol-alkyne and a thiol-disulfide exchange. 25980911 6 18 theme novel 755:759 arg1 strategy 772:779 This novel enrichment strategy 750:779 This novel enrichment strategy 750:779 This novel enrichment strategy could be used for O-GlcNAcome analysis of biological samples. 25980911 0 19 theme novel 47:51 arg1 thiol-alkyne 53:64 novel thiol-alkyne 47:64 novel thiol-alkyne 47:64 Enrichment of O-GlcNAc-modified peptides using novel thiol-alkyne and thiol-disulfide exchange. 25980911 3 20 theme -catalyzed 465:474 arg1 cycloaddition 489:501 a copper(I)-catalyzed azide-alkyne cycloaddition 454:501 a copper(I)-catalyzed azide-alkyne cycloaddition 454:501 Then, the azide moiety was reacted with thiol-alkyne through a copper(I)-catalyzed azide-alkyne cycloaddition. 25980911 1 21 link O-linked 155:162 arg1 peptides 206:213 O-linked β-N-acetylglucosamine (O-GlcNAc)-modified peptides 155:213 O-linked β-N-acetylglucosamine (O-GlcNAc)-modified peptides 155:213 We have developed a selective method for the enrichment of O-linked β-N-acetylglucosamine (O-GlcNAc)-modified peptides, which uses a newly synthesized thiol-alkyne and a thiol-disulfide exchange. 25980911 0 22 theme peptides 32:39 arg1 Enrichment 0:9 Enrichment 0:9 Enrichment of O-GlcNAc-modified peptides 0:39 Enrichment of O-GlcNAc-modified peptides using novel thiol-alkyne and thiol-disulfide exchange. 25980911 3 23 theme azide-alkyne 476:487 arg1 cycloaddition 489:501 a copper(I)-catalyzed azide-alkyne cycloaddition 454:501 a copper(I)-catalyzed azide-alkyne cycloaddition 454:501 Then, the azide moiety was reacted with thiol-alkyne through a copper(I)-catalyzed azide-alkyne cycloaddition. 25980911 2 24 theme GalNAc 378:383 arg1 analog 385:390 an azide-containing GalNAc analog 358:390 an azide-containing GalNAc analog 358:390 First, O-GlcNAc-modified peptides were enzymatically labeled with an azide-containing GalNAc analog. 25980911 4 25 theme thiol-disulfide 582:596 arg1 exchange 598:605 a thiol-disulfide exchange 580:605 a thiol-disulfide exchange 580:605 The thiol-modified peptides were enriched with thiol-reactive resin through a thiol-disulfide exchange. 25980911 6 26 theme samples 834:840 arg1 analysis 811:818 O-GlcNAcome analysis 799:818 O-GlcNAcome analysis of biological samples 799:840 This novel enrichment strategy could be used for O-GlcNAcome analysis of biological samples. 25980911 2 27 theme azide-containing 361:376 arg1 analog 385:390 an azide-containing GalNAc analog 358:390 an azide-containing GalNAc analog 358:390 First, O-GlcNAc-modified peptides were enzymatically labeled with an azide-containing GalNAc analog. 25980911 6 28 theme biological 823:832 arg1 samples 834:840 biological samples 823:840 biological samples 823:840 This novel enrichment strategy could be used for O-GlcNAcome analysis of biological samples. 25980911 1 29 theme O-linked 155:162 arg1 peptides 206:213 O-linked β-N-acetylglucosamine (O-GlcNAc)-modified peptides 155:213 O-linked β-N-acetylglucosamine (O-GlcNAc)-modified peptides 155:213 We have developed a selective method for the enrichment of O-linked β-N-acetylglucosamine (O-GlcNAc)-modified peptides, which uses a newly synthesized thiol-alkyne and a thiol-disulfide exchange. 25980911 1 30 theme synthesized 235:245 arg1 thiol-alkyne 247:258 a newly synthesized thiol-alkyne 227:258 a newly synthesized thiol-alkyne 227:258 We have developed a selective method for the enrichment of O-linked β-N-acetylglucosamine (O-GlcNAc)-modified peptides, which uses a newly synthesized thiol-alkyne and a thiol-disulfide exchange. 25980911 0 31 theme thiol-disulfide 70:84 arg1 exchange 86:93 thiol-disulfide exchange 70:93 thiol-disulfide exchange 70:93 Enrichment of O-GlcNAc-modified peptides using novel thiol-alkyne and thiol-disulfide exchange. 25980911 2 32 dep First 292:296 arg1 O-GlcNAc-modified 299:315 O-GlcNAc-modified 299:315 O-GlcNAc-modified 299:315 First, O-GlcNAc-modified peptides were enzymatically labeled with an azide-containing GalNAc analog. 28207246 3 0 dep aspartate 371:379 arg1 occurred 496:503 occurred 496:503 occurred was not examined 496:520 Replacing glutamate with aspartate in an HCF-1 proteolytic repeat was shown to prevent peptide backbone cleavage, but whether aspartate glycosylation occurred was not examined. 28207246 3 0 dep aspartate 371:379 arg1 shown 416:420 shown 416:420 was shown to prevent peptide backbone cleavage 412:457 Replacing glutamate with aspartate in an HCF-1 proteolytic repeat was shown to prevent peptide backbone cleavage, but whether aspartate glycosylation occurred was not examined. 28207246 7 1 theme poly 1174:1177 arg1 ation 1191:1195 poly(ADP-ribosyl)ation 1174:1195 poly(ADP-ribosyl)ation 1174:1195 In addition to OGT, enzymes that may catalyze aspartate to isoaspartate isomerization include PARPs, enzymes known to ribosylate aspartate residues in the process of poly(ADP-ribosyl)ation. 28207246 2 2 from glycosylation 318:330 arg1 glutamate 335:343 glutamate 335:343 glutamate 335:343 It also cleaves Host cell factor 1 (HCF-1) by a mechanism in which the first step involves glycosylation on glutamate. 28207246 1 3 theme cytoplasmic 181:191 arg1 proteins 193:200 numerous nuclear and cytoplasmic proteins 160:200 numerous nuclear and cytoplasmic proteins 160:200 O-Linked β-N-acetylglucosamine transferase (OGT) is an essential human enzyme that glycosylates numerous nuclear and cytoplasmic proteins on serine and threonine. 28207246 4 4 from glutamate 603:611 arg1 substrate 653:661 an otherwise identical model peptide substrate 616:661 an otherwise identical model peptide substrate 616:661 We report here that OGT glycosylates aspartate much faster than it glycosylates glutamate in an otherwise identical model peptide substrate; moreover, once formed, the glycosyl aspartate reacts further to form a succinimide intermediate that hydrolyzes to produce the corresponding isoaspartyl peptide. 28207246 1 5 theme β-N-acetylglucosamine 73:93 arg1 OGT 108:110 OGT 108:110 OGT 108:110 O-Linked β-N-acetylglucosamine transferase (OGT) is an essential human enzyme that glycosylates numerous nuclear and cytoplasmic proteins on serine and threonine. 28207246 1 5 theme β-N-acetylglucosamine 73:93 arg1 transferase 95:105 O-Linked β-N-acetylglucosamine transferase 64:105 O-Linked β-N-acetylglucosamine transferase (OGT) 64:111 O-Linked β-N-acetylglucosamine transferase (OGT) is an essential human enzyme that glycosylates numerous nuclear and cytoplasmic proteins on serine and threonine. 28207246 1 5 theme β-N-acetylglucosamine 73:93 arg1 enzyme 135:140 an essential human enzyme 116:140 an essential human enzyme that glycosylates numerous nuclear and cytoplasmic proteins on serine and threonine 116:224 O-Linked β-N-acetylglucosamine transferase (OGT) is an essential human enzyme that glycosylates numerous nuclear and cytoplasmic proteins on serine and threonine. 28207246 4 6 theme glycosyl 691:698 arg1 aspartate 700:708 the glycosyl aspartate 687:708 the glycosyl aspartate 687:708 We report here that OGT glycosylates aspartate much faster than it glycosylates glutamate in an otherwise identical model peptide substrate; moreover, once formed, the glycosyl aspartate reacts further to form a succinimide intermediate that hydrolyzes to produce the corresponding isoaspartyl peptide. 28207246 3 7 dep occurred 496:503 arg1 examined 513:520 examined 513:520 occurred was not examined 496:520 Replacing glutamate with aspartate in an HCF-1 proteolytic repeat was shown to prevent peptide backbone cleavage, but whether aspartate glycosylation occurred was not examined. 28207246 3 8 theme peptide 433:439 arg1 cleavage 450:457 peptide backbone cleavage 433:457 peptide backbone cleavage 433:457 Replacing glutamate with aspartate in an HCF-1 proteolytic repeat was shown to prevent peptide backbone cleavage, but whether aspartate glycosylation occurred was not examined. 28207246 0 9 theme Aspartate 0:8 arg1 Glycosylation 10:22 Aspartate Glycosylation 0:22 Aspartate Glycosylation 0:22 Aspartate Glycosylation Triggers Isomerization to Isoaspartate. 28207246 3 10 theme backbone 441:448 arg1 cleavage 450:457 peptide backbone cleavage 433:457 peptide backbone cleavage 433:457 Replacing glutamate with aspartate in an HCF-1 proteolytic repeat was shown to prevent peptide backbone cleavage, but whether aspartate glycosylation occurred was not examined. 28207246 5 11 theme Aspartate-to-isoaspartate 826:850 arg1 isomerization 852:864 Aspartate-to-isoaspartate isomerization 826:864 Aspartate-to-isoaspartate isomerization in proteins 826:876 Aspartate-to-isoaspartate isomerization in proteins occurs in cells but was previously thought to be exclusively non-enzymatic. 28207246 5 12 from isomerization 852:864 arg1 proteins 869:876 proteins 869:876 proteins 869:876 Aspartate-to-isoaspartate isomerization in proteins occurs in cells but was previously thought to be exclusively non-enzymatic. 28207246 4 13 theme succinimide 735:745 arg1 intermediate 747:758 a succinimide intermediate 733:758 a succinimide intermediate that hydrolyzes to produce the corresponding isoaspartyl peptide 733:823 We report here that OGT glycosylates aspartate much faster than it glycosylates glutamate in an otherwise identical model peptide substrate; moreover, once formed, the glycosyl aspartate reacts further to form a succinimide intermediate that hydrolyzes to produce the corresponding isoaspartyl peptide. 28207246 3 14 theme HCF-1 387:391 arg1 repeat 405:410 an HCF-1 proteolytic repeat 384:410 an HCF-1 proteolytic repeat 384:410 Replacing glutamate with aspartate in an HCF-1 proteolytic repeat was shown to prevent peptide backbone cleavage, but whether aspartate glycosylation occurred was not examined. 28207246 7 15 theme aspartate 1137:1145 arg1 residues 1147:1154 aspartate residues 1137:1154 aspartate residues 1137:1154 In addition to OGT, enzymes that may catalyze aspartate to isoaspartate isomerization include PARPs, enzymes known to ribosylate aspartate residues in the process of poly(ADP-ribosyl)ation. 28207246 4 16 gly glycosylates 590:601 arg1 glutamate 603:611 glutamate 603:611 glutamate in an otherwise identical model peptide substrate 603:661 We report here that OGT glycosylates aspartate much faster than it glycosylates glutamate in an otherwise identical model peptide substrate; moreover, once formed, the glycosyl aspartate reacts further to form a succinimide intermediate that hydrolyzes to produce the corresponding isoaspartyl peptide. 28207246 2 17 theme first 298:302 arg1 step 304:307 the first step 294:307 the first step 294:307 It also cleaves Host cell factor 1 (HCF-1) by a mechanism in which the first step involves glycosylation on glutamate. 28207246 4 18 theme peptide 645:651 arg1 substrate 653:661 an otherwise identical model peptide substrate 616:661 an otherwise identical model peptide substrate 616:661 We report here that OGT glycosylates aspartate much faster than it glycosylates glutamate in an otherwise identical model peptide substrate; moreover, once formed, the glycosyl aspartate reacts further to form a succinimide intermediate that hydrolyzes to produce the corresponding isoaspartyl peptide. 28207246 4 19 theme faster 575:580 arg1 aspartate 560:568 aspartate 560:568 aspartate much faster than it glycosylates glutamate in an otherwise identical model peptide substrate 560:661 We report here that OGT glycosylates aspartate much faster than it glycosylates glutamate in an otherwise identical model peptide substrate; moreover, once formed, the glycosyl aspartate reacts further to form a succinimide intermediate that hydrolyzes to produce the corresponding isoaspartyl peptide. 28207246 1 20 theme essential 119:127 arg1 enzyme 135:140 an essential human enzyme 116:140 an essential human enzyme that glycosylates numerous nuclear and cytoplasmic proteins on serine and threonine 116:224 O-Linked β-N-acetylglucosamine transferase (OGT) is an essential human enzyme that glycosylates numerous nuclear and cytoplasmic proteins on serine and threonine. 28207246 1 20 theme essential 119:127 arg1 transferase 95:105 O-Linked β-N-acetylglucosamine transferase 64:105 O-Linked β-N-acetylglucosamine transferase (OGT) 64:111 O-Linked β-N-acetylglucosamine transferase (OGT) is an essential human enzyme that glycosylates numerous nuclear and cytoplasmic proteins on serine and threonine. 28207246 4 21 theme model 639:643 arg1 substrate 653:661 an otherwise identical model peptide substrate 616:661 an otherwise identical model peptide substrate 616:661 We report here that OGT glycosylates aspartate much faster than it glycosylates glutamate in an otherwise identical model peptide substrate; moreover, once formed, the glycosyl aspartate reacts further to form a succinimide intermediate that hydrolyzes to produce the corresponding isoaspartyl peptide. 28207246 1 22 gly glycosylates 147:158 arg1 proteins 193:200 numerous nuclear and cytoplasmic proteins 160:200 numerous nuclear and cytoplasmic proteins 160:200 O-Linked β-N-acetylglucosamine transferase (OGT) is an essential human enzyme that glycosylates numerous nuclear and cytoplasmic proteins on serine and threonine. 28207246 7 23 theme ation 1191:1195 arg1 process 1163:1169 the process 1159:1169 the process of poly(ADP-ribosyl)ation 1159:1195 In addition to OGT, enzymes that may catalyze aspartate to isoaspartate isomerization include PARPs, enzymes known to ribosylate aspartate residues in the process of poly(ADP-ribosyl)ation. 28207246 2 24 theme cell 248:251 arg1 factor 253:258 Host cell factor 1 243:260 Host cell factor 1 (HCF-1) 243:268 It also cleaves Host cell factor 1 (HCF-1) by a mechanism in which the first step involves glycosylation on glutamate. 28207246 2 24 theme cell 248:251 arg1 HCF-1 263:267 HCF-1 263:267 HCF-1 263:267 It also cleaves Host cell factor 1 (HCF-1) by a mechanism in which the first step involves glycosylation on glutamate. 28207246 4 25 gly glycosylates 547:558 arg1 aspartate 560:568 aspartate 560:568 aspartate much faster than it glycosylates glutamate in an otherwise identical model peptide substrate 560:661 We report here that OGT glycosylates aspartate much faster than it glycosylates glutamate in an otherwise identical model peptide substrate; moreover, once formed, the glycosyl aspartate reacts further to form a succinimide intermediate that hydrolyzes to produce the corresponding isoaspartyl peptide. 28207246 3 26 theme proteolytic 393:403 arg1 repeat 405:410 an HCF-1 proteolytic repeat 384:410 an HCF-1 proteolytic repeat 384:410 Replacing glutamate with aspartate in an HCF-1 proteolytic repeat was shown to prevent peptide backbone cleavage, but whether aspartate glycosylation occurred was not examined. 28207246 2 27 theme Host 243:246 arg1 factor 253:258 Host cell factor 1 243:260 Host cell factor 1 (HCF-1) 243:268 It also cleaves Host cell factor 1 (HCF-1) by a mechanism in which the first step involves glycosylation on glutamate. 28207246 2 27 theme Host 243:246 arg1 HCF-1 263:267 HCF-1 263:267 HCF-1 263:267 It also cleaves Host cell factor 1 (HCF-1) by a mechanism in which the first step involves glycosylation on glutamate. 28207246 1 28 theme human 129:133 arg1 enzyme 135:140 an essential human enzyme 116:140 an essential human enzyme that glycosylates numerous nuclear and cytoplasmic proteins on serine and threonine 116:224 O-Linked β-N-acetylglucosamine transferase (OGT) is an essential human enzyme that glycosylates numerous nuclear and cytoplasmic proteins on serine and threonine. 28207246 1 28 theme human 129:133 arg1 transferase 95:105 O-Linked β-N-acetylglucosamine transferase 64:105 O-Linked β-N-acetylglucosamine transferase (OGT) 64:111 O-Linked β-N-acetylglucosamine transferase (OGT) is an essential human enzyme that glycosylates numerous nuclear and cytoplasmic proteins on serine and threonine. 28207246 7 29 theme ADP-ribosyl 1179:1189 arg1 ation 1191:1195 poly(ADP-ribosyl)ation 1174:1195 poly(ADP-ribosyl)ation 1174:1195 In addition to OGT, enzymes that may catalyze aspartate to isoaspartate isomerization include PARPs, enzymes known to ribosylate aspartate residues in the process of poly(ADP-ribosyl)ation. 28207246 7 30 theme isoaspartate 1067:1078 arg1 isomerization 1080:1092 isoaspartate isomerization 1067:1092 isoaspartate isomerization 1067:1092 In addition to OGT, enzymes that may catalyze aspartate to isoaspartate isomerization include PARPs, enzymes known to ribosylate aspartate residues in the process of poly(ADP-ribosyl)ation. 28207246 4 31 theme isoaspartyl 805:815 arg1 peptide 817:823 the corresponding isoaspartyl peptide 787:823 the corresponding isoaspartyl peptide 787:823 We report here that OGT glycosylates aspartate much faster than it glycosylates glutamate in an otherwise identical model peptide substrate; moreover, once formed, the glycosyl aspartate reacts further to form a succinimide intermediate that hydrolyzes to produce the corresponding isoaspartyl peptide. 28207246 3 32 theme aspartate 472:480 arg1 glycosylation 482:494 aspartate glycosylation 472:494 aspartate glycosylation 472:494 Replacing glutamate with aspartate in an HCF-1 proteolytic repeat was shown to prevent peptide backbone cleavage, but whether aspartate glycosylation occurred was not examined. 28207246 2 33 gly glycosylation 318:330 arg1 mechanism 275:283 a mechanism 273:283 a mechanism in which the first step involves glycosylation on glutamate 273:343 It also cleaves Host cell factor 1 (HCF-1) by a mechanism in which the first step involves glycosylation on glutamate. 28207246 2 33 gly glycosylation 318:330 arg1 glutamate 335:343 glutamate 335:343 glutamate 335:343 It also cleaves Host cell factor 1 (HCF-1) by a mechanism in which the first step involves glycosylation on glutamate. 28207246 4 34 theme corresponding 791:803 arg1 peptide 817:823 the corresponding isoaspartyl peptide 787:823 the corresponding isoaspartyl peptide 787:823 We report here that OGT glycosylates aspartate much faster than it glycosylates glutamate in an otherwise identical model peptide substrate; moreover, once formed, the glycosyl aspartate reacts further to form a succinimide intermediate that hydrolyzes to produce the corresponding isoaspartyl peptide. 28207246 1 35 theme numerous 160:167 arg1 proteins 193:200 numerous nuclear and cytoplasmic proteins 160:200 numerous nuclear and cytoplasmic proteins 160:200 O-Linked β-N-acetylglucosamine transferase (OGT) is an essential human enzyme that glycosylates numerous nuclear and cytoplasmic proteins on serine and threonine. 28207246 4 36 theme identical 629:637 arg1 substrate 653:661 an otherwise identical model peptide substrate 616:661 an otherwise identical model peptide substrate 616:661 We report here that OGT glycosylates aspartate much faster than it glycosylates glutamate in an otherwise identical model peptide substrate; moreover, once formed, the glycosyl aspartate reacts further to form a succinimide intermediate that hydrolyzes to produce the corresponding isoaspartyl peptide. 28207246 1 37 theme O-Linked 64:71 arg1 OGT 108:110 OGT 108:110 OGT 108:110 O-Linked β-N-acetylglucosamine transferase (OGT) is an essential human enzyme that glycosylates numerous nuclear and cytoplasmic proteins on serine and threonine. 28207246 1 37 theme O-Linked 64:71 arg1 transferase 95:105 O-Linked β-N-acetylglucosamine transferase 64:105 O-Linked β-N-acetylglucosamine transferase (OGT) 64:111 O-Linked β-N-acetylglucosamine transferase (OGT) is an essential human enzyme that glycosylates numerous nuclear and cytoplasmic proteins on serine and threonine. 28207246 1 37 theme O-Linked 64:71 arg1 enzyme 135:140 an essential human enzyme 116:140 an essential human enzyme that glycosylates numerous nuclear and cytoplasmic proteins on serine and threonine 116:224 O-Linked β-N-acetylglucosamine transferase (OGT) is an essential human enzyme that glycosylates numerous nuclear and cytoplasmic proteins on serine and threonine. 28207246 1 38 theme nuclear 169:175 arg1 proteins 193:200 numerous nuclear and cytoplasmic proteins 160:200 numerous nuclear and cytoplasmic proteins 160:200 O-Linked β-N-acetylglucosamine transferase (OGT) is an essential human enzyme that glycosylates numerous nuclear and cytoplasmic proteins on serine and threonine. 26970331 6 0 theme immobilized 870:880 arg1 heparin 903:909 immobilized low molecular weight heparin 870:909 immobilized low molecular weight heparin 870:909 For this purpose, proteins were pulled down from immobilized low molecular weight heparin, heparan sulfate, and dermatan sulfate under different conditions and were identified by nano-LC/MS². 26970331 3 1 dep ability 375:381 arg1 interact 386:393 interact 386:393 to interact with diverse proteins 383:415 Due to their ability to interact with diverse proteins and to modulate their biologic functions, GAGs are main drivers of mammalian biology. 26970331 3 1 dep ability 375:381 arg1 modulate 424:431 modulate 424:431 to modulate their biologic functions 421:456 Due to their ability to interact with diverse proteins and to modulate their biologic functions, GAGs are main drivers of mammalian biology. 26970331 10 2 theme GAG-binding 1498:1508 arg1 properties 1510:1519 well-known GAG-binding properties 1487:1519 well-known GAG-binding properties 1487:1519 On top of proteins with well-known GAG-binding properties we have identified formerly unknown GAG binders. 26970331 8 3 theme glycan 1270:1275 arg1 ligands 1277:1283 all three glycan ligands 1260:1283 all three glycan ligands 1260:1283 We were able to differentiate between proteins that bound to all three glycan ligands and proteins that showed selective binding to one or two glycan ligands. 26970331 11 4 theme processes 1704:1712 arg1 variety 1682:1688 a variety 1680:1688 a variety of biological processes 1680:1712 Functional annotation of the identified GAG-binding proteins showed clusters of proteins that are involved in a variety of biological processes. 26970331 11 4 theme processes 1704:1712 arg1 processes 1704:1712 biological processes 1693:1712 biological processes 1693:1712 Functional annotation of the identified GAG-binding proteins showed clusters of proteins that are involved in a variety of biological processes. 26970331 6 5 theme different 956:964 arg1 conditions 966:975 different conditions 956:975 different conditions 956:975 For this purpose, proteins were pulled down from immobilized low molecular weight heparin, heparan sulfate, and dermatan sulfate under different conditions and were identified by nano-LC/MS². 26970331 11 6 theme proteins 1650:1657 arg1 clusters 1638:1645 clusters 1638:1645 clusters of proteins that are involved in a variety of biological processes 1638:1712 Functional annotation of the identified GAG-binding proteins showed clusters of proteins that are involved in a variety of biological processes. 26970331 1 7 theme all 191:193 arg1 cells 202:206 almost all animal cells 184:206 almost all animal cells 184:206 Glycosaminoglycans (GAGs) are linear, highly sulfated polysaccharides expressed by almost all animal cells. 26970331 12 8 theme GAG-binding 1772:1782 arg1 proteins 1784:1791 GAG-binding proteins 1772:1791 GAG-binding proteins 1772:1791 The method described here is well suited for identifying GAG-binding proteins and for comparing human subproteomes with respect to binding to different GAG classes. 26970331 9 9 theme different 1404:1412 arg1 affinities 1422:1431 different binding affinities 1404:1431 different binding affinities toward different GAG ligands 1404:1460 Moreover, step-gradient salt elution revealed different binding affinities toward different GAG ligands. 26970331 8 10 theme selective 1310:1318 arg1 binding 1320:1326 selective binding 1310:1326 selective binding to one or two glycan ligands 1310:1355 We were able to differentiate between proteins that bound to all three glycan ligands and proteins that showed selective binding to one or two glycan ligands. 26970331 6 11 theme dermatan 933:940 arg1 sulfate 942:948 dermatan sulfate 933:948 dermatan sulfate 933:948 For this purpose, proteins were pulled down from immobilized low molecular weight heparin, heparan sulfate, and dermatan sulfate under different conditions and were identified by nano-LC/MS². 26970331 7 12 theme GAG-binding 1149:1159 arg1 specificity/selectivity 1161:1183 their GAG-binding specificity/selectivity 1143:1183 their GAG-binding specificity/selectivity 1143:1183 Four hundred and fifty eight human GAG binding proteins have been identified, whereas plasma proteins showed clear differences in their GAG-binding specificity/selectivity and affinity. 26970331 7 13 from differences 1128:1138 arg1 affinity 1189:1196 affinity 1189:1196 affinity 1189:1196 Four hundred and fifty eight human GAG binding proteins have been identified, whereas plasma proteins showed clear differences in their GAG-binding specificity/selectivity and affinity. 26970331 7 13 from differences 1128:1138 arg1 specificity/selectivity 1161:1183 their GAG-binding specificity/selectivity 1143:1183 their GAG-binding specificity/selectivity 1143:1183 Four hundred and fifty eight human GAG binding proteins have been identified, whereas plasma proteins showed clear differences in their GAG-binding specificity/selectivity and affinity. 26970331 7 14 theme binding 1052:1058 arg1 proteins 1060:1067 Four hundred and fifty eight human GAG binding proteins 1013:1067 Four hundred and fifty eight human GAG binding proteins 1013:1067 Four hundred and fifty eight human GAG binding proteins have been identified, whereas plasma proteins showed clear differences in their GAG-binding specificity/selectivity and affinity. 26970331 5 15 theme human 798:802 arg1 proteome 811:818 the human plasma proteome 794:818 the human plasma proteome 794:818 The aim of this study was therefore to investigate the human GAG binding proteome of different sources by using the major GAG classes as ligands, and to explore the GAG-binding selectivity of the human plasma proteome. 26970331 2 16 theme core 295:298 arg1 proteins 300:307 different core proteins 285:307 different core proteins on the cell surface and in the extracellular matrix 285:359 They occur as soluble molecules, or form proteoglycans by being O-linked to different core proteins on the cell surface and in the extracellular matrix. 26970331 1 17 theme animal 195:200 arg1 cells 202:206 almost all animal cells 184:206 almost all animal cells 184:206 Glycosaminoglycans (GAGs) are linear, highly sulfated polysaccharides expressed by almost all animal cells. 26970331 5 18 theme major 718:722 arg1 classes 728:734 the major GAG classes 714:734 the major GAG classes as ligands 714:745 The aim of this study was therefore to investigate the human GAG binding proteome of different sources by using the major GAG classes as ligands, and to explore the GAG-binding selectivity of the human plasma proteome. 26970331 11 19 theme Functional 1570:1579 arg1 annotation 1581:1590 Functional annotation 1570:1590 Functional annotation of the identified GAG-binding proteins 1570:1629 Functional annotation of the identified GAG-binding proteins showed clusters of proteins that are involved in a variety of biological processes. 26970331 2 20 theme different 285:293 arg1 proteins 300:307 different core proteins 285:307 different core proteins on the cell surface and in the extracellular matrix 285:359 They occur as soluble molecules, or form proteoglycans by being O-linked to different core proteins on the cell surface and in the extracellular matrix. 26970331 6 21 theme heparan 912:918 arg1 sulfate 920:926 heparan sulfate 912:926 heparan sulfate 912:926 For this purpose, proteins were pulled down from immobilized low molecular weight heparin, heparan sulfate, and dermatan sulfate under different conditions and were identified by nano-LC/MS². 26970331 7 22 theme human 1042:1046 arg1 proteins 1060:1067 Four hundred and fifty eight human GAG binding proteins 1013:1067 Four hundred and fifty eight human GAG binding proteins 1013:1067 Four hundred and fifty eight human GAG binding proteins have been identified, whereas plasma proteins showed clear differences in their GAG-binding specificity/selectivity and affinity. 26970331 10 23 theme GAG 1557:1559 arg1 binders 1561:1567 formerly unknown GAG binders 1540:1567 formerly unknown GAG binders 1540:1567 On top of proteins with well-known GAG-binding properties we have identified formerly unknown GAG binders. 26970331 8 24 theme glycan 1342:1347 arg1 ligands 1349:1355 one or two glycan ligands 1331:1355 one or two glycan ligands 1331:1355 We were able to differentiate between proteins that bound to all three glycan ligands and proteins that showed selective binding to one or two glycan ligands. 26970331 12 25 theme different 1857:1865 arg1 classes 1871:1877 different GAG classes 1857:1877 different GAG classes 1857:1877 The method described here is well suited for identifying GAG-binding proteins and for comparing human subproteomes with respect to binding to different GAG classes. 26970331 9 26 theme different 1440:1448 arg1 ligands 1454:1460 different GAG ligands 1440:1460 different GAG ligands 1440:1460 Moreover, step-gradient salt elution revealed different binding affinities toward different GAG ligands. 26970331 5 27 theme GAG-binding 767:777 arg1 selectivity 779:789 the GAG-binding selectivity 763:789 the GAG-binding selectivity of the human plasma proteome 763:818 The aim of this study was therefore to investigate the human GAG binding proteome of different sources by using the major GAG classes as ligands, and to explore the GAG-binding selectivity of the human plasma proteome. 26970331 4 28 theme human 536:540 arg1 proteome 554:561 the human GAG binding proteome 532:561 the human GAG binding proteome 532:561 However, to the present day, the human GAG binding proteome has only been insufficiently explored. 26970331 5 29 theme study 618:622 arg1 aim 606:608 The aim 602:608 The aim of this study 602:622 The aim of this study was therefore to investigate the human GAG binding proteome of different sources by using the major GAG classes as ligands, and to explore the GAG-binding selectivity of the human plasma proteome. 26970331 9 30 theme GAG 1450:1452 arg1 ligands 1454:1460 different GAG ligands 1440:1460 different GAG ligands 1440:1460 Moreover, step-gradient salt elution revealed different binding affinities toward different GAG ligands. 26970331 0 31 theme interaction 40:50 arg1 network 52:58 the glycosaminoglycan-protein interaction network 10:58 the glycosaminoglycan-protein interaction network 10:58 Exploring the glycosaminoglycan-protein interaction network by glycan-mediated pull-down proteomics. 26970331 10 32 theme well-known 1487:1496 arg1 properties 1510:1519 well-known GAG-binding properties 1487:1519 well-known GAG-binding properties 1487:1519 On top of proteins with well-known GAG-binding properties we have identified formerly unknown GAG binders. 26970331 2 33 theme cell 316:319 arg1 surface 321:327 the cell surface 312:327 the cell surface 312:327 They occur as soluble molecules, or form proteoglycans by being O-linked to different core proteins on the cell surface and in the extracellular matrix. 26970331 0 34 theme glycosaminoglycan-protein 14:38 arg1 network 52:58 the glycosaminoglycan-protein interaction network 10:58 the glycosaminoglycan-protein interaction network 10:58 Exploring the glycosaminoglycan-protein interaction network by glycan-mediated pull-down proteomics. 26970331 4 35 theme binding 546:552 arg1 proteome 554:561 the human GAG binding proteome 532:561 the human GAG binding proteome 532:561 However, to the present day, the human GAG binding proteome has only been insufficiently explored. 26970331 1 36 theme linear 131:136 arg1 Glycosaminoglycans 101:118 Glycosaminoglycans 101:118 Glycosaminoglycans (GAGs) 101:125 Glycosaminoglycans (GAGs) are linear, highly sulfated polysaccharides expressed by almost all animal cells. 26970331 1 36 theme linear 131:136 arg1 polysaccharides 155:169 linear, highly sulfated polysaccharides 131:169 linear, highly sulfated polysaccharides expressed by almost all animal cells 131:206 Glycosaminoglycans (GAGs) are linear, highly sulfated polysaccharides expressed by almost all animal cells. 26970331 9 37 theme binding 1414:1420 arg1 affinities 1422:1431 different binding affinities 1404:1431 different binding affinities toward different GAG ligands 1404:1460 Moreover, step-gradient salt elution revealed different binding affinities toward different GAG ligands. 26970331 3 38 theme main 468:471 arg1 GAGs 459:462 GAGs 459:462 GAGs 459:462 Due to their ability to interact with diverse proteins and to modulate their biologic functions, GAGs are main drivers of mammalian biology. 26970331 3 38 theme main 468:471 arg1 drivers 473:479 main drivers 468:479 main drivers of mammalian biology 468:500 Due to their ability to interact with diverse proteins and to modulate their biologic functions, GAGs are main drivers of mammalian biology. 26970331 4 39 theme GAG 542:544 arg1 proteome 554:561 the human GAG binding proteome 532:561 the human GAG binding proteome 532:561 However, to the present day, the human GAG binding proteome has only been insufficiently explored. 26970331 5 40 theme different 687:695 arg1 sources 697:703 different sources 687:703 different sources 687:703 The aim of this study was therefore to investigate the human GAG binding proteome of different sources by using the major GAG classes as ligands, and to explore the GAG-binding selectivity of the human plasma proteome. 26970331 5 41 theme plasma 804:809 arg1 proteome 811:818 the human plasma proteome 794:818 the human plasma proteome 794:818 The aim of this study was therefore to investigate the human GAG binding proteome of different sources by using the major GAG classes as ligands, and to explore the GAG-binding selectivity of the human plasma proteome. 26970331 3 42 theme biologic 439:446 arg1 functions 448:456 their biologic functions 433:456 their biologic functions 433:456 Due to their ability to interact with diverse proteins and to modulate their biologic functions, GAGs are main drivers of mammalian biology. 26970331 4 43 theme present 519:525 arg1 day 527:529 the present day 515:529 the present day 515:529 However, to the present day, the human GAG binding proteome has only been insufficiently explored. 26970331 5 44 theme sources 697:703 arg1 proteome 675:682 the human GAG binding proteome 653:682 the human GAG binding proteome of different sources 653:703 The aim of this study was therefore to investigate the human GAG binding proteome of different sources by using the major GAG classes as ligands, and to explore the GAG-binding selectivity of the human plasma proteome. 26970331 11 45 theme biological 1693:1702 arg1 processes 1704:1712 biological processes 1693:1712 biological processes 1693:1712 Functional annotation of the identified GAG-binding proteins showed clusters of proteins that are involved in a variety of biological processes. 26970331 7 46 theme clear 1122:1126 arg1 differences 1128:1138 clear differences 1122:1138 clear differences in their GAG-binding specificity/selectivity and affinity 1122:1196 Four hundred and fifty eight human GAG binding proteins have been identified, whereas plasma proteins showed clear differences in their GAG-binding specificity/selectivity and affinity. 26970331 11 47 theme identified 1599:1608 arg1 proteins 1622:1629 the identified GAG-binding proteins 1595:1629 the identified GAG-binding proteins 1595:1629 Functional annotation of the identified GAG-binding proteins showed clusters of proteins that are involved in a variety of biological processes. 26970331 5 48 theme proteome 811:818 arg1 selectivity 779:789 the GAG-binding selectivity 763:789 the GAG-binding selectivity of the human plasma proteome 763:818 The aim of this study was therefore to investigate the human GAG binding proteome of different sources by using the major GAG classes as ligands, and to explore the GAG-binding selectivity of the human plasma proteome. 26970331 0 49 theme pull-down 79:87 arg1 proteomics 89:98 glycan-mediated pull-down proteomics 63:98 glycan-mediated pull-down proteomics 63:98 Exploring the glycosaminoglycan-protein interaction network by glycan-mediated pull-down proteomics. 26970331 12 50 theme GAG 1867:1869 arg1 classes 1871:1877 different GAG classes 1857:1877 different GAG classes 1857:1877 The method described here is well suited for identifying GAG-binding proteins and for comparing human subproteomes with respect to binding to different GAG classes. 26970331 10 51 theme unknown 1549:1555 arg1 binders 1561:1567 formerly unknown GAG binders 1540:1567 formerly unknown GAG binders 1540:1567 On top of proteins with well-known GAG-binding properties we have identified formerly unknown GAG binders. 26970331 11 52 theme GAG-binding 1610:1620 arg1 proteins 1622:1629 the identified GAG-binding proteins 1595:1629 the identified GAG-binding proteins 1595:1629 Functional annotation of the identified GAG-binding proteins showed clusters of proteins that are involved in a variety of biological processes. 26970331 3 53 theme mammalian 484:492 arg1 biology 494:500 mammalian biology 484:500 mammalian biology 484:500 Due to their ability to interact with diverse proteins and to modulate their biologic functions, GAGs are main drivers of mammalian biology. 26970331 0 54 theme glycan-mediated 63:77 arg1 proteomics 89:98 glycan-mediated pull-down proteomics 63:98 glycan-mediated pull-down proteomics 63:98 Exploring the glycosaminoglycan-protein interaction network by glycan-mediated pull-down proteomics. 26970331 6 55 theme weight 896:901 arg1 heparin 903:909 immobilized low molecular weight heparin 870:909 immobilized low molecular weight heparin 870:909 For this purpose, proteins were pulled down from immobilized low molecular weight heparin, heparan sulfate, and dermatan sulfate under different conditions and were identified by nano-LC/MS². 26970331 5 56 theme human 657:661 arg1 proteome 675:682 the human GAG binding proteome 653:682 the human GAG binding proteome of different sources 653:703 The aim of this study was therefore to investigate the human GAG binding proteome of different sources by using the major GAG classes as ligands, and to explore the GAG-binding selectivity of the human plasma proteome. 26970331 2 57 theme extracellular 340:352 arg1 matrix 354:359 the extracellular matrix 336:359 the extracellular matrix 336:359 They occur as soluble molecules, or form proteoglycans by being O-linked to different core proteins on the cell surface and in the extracellular matrix. 26970331 10 58 with proteins 1473:1480 arg1 properties 1510:1519 well-known GAG-binding properties 1487:1519 well-known GAG-binding properties 1487:1519 On top of proteins with well-known GAG-binding properties we have identified formerly unknown GAG binders. 26970331 6 59 theme molecular 886:894 arg1 heparin 903:909 immobilized low molecular weight heparin 870:909 immobilized low molecular weight heparin 870:909 For this purpose, proteins were pulled down from immobilized low molecular weight heparin, heparan sulfate, and dermatan sulfate under different conditions and were identified by nano-LC/MS². 26970331 5 60 theme GAG 663:665 arg1 proteome 675:682 the human GAG binding proteome 653:682 the human GAG binding proteome of different sources 653:703 The aim of this study was therefore to investigate the human GAG binding proteome of different sources by using the major GAG classes as ligands, and to explore the GAG-binding selectivity of the human plasma proteome. 26970331 2 61 theme soluble 223:229 arg1 proteoglycans 250:262 proteoglycans 250:262 proteoglycans 250:262 They occur as soluble molecules, or form proteoglycans by being O-linked to different core proteins on the cell surface and in the extracellular matrix. 26970331 2 61 theme soluble 223:229 arg1 molecules 231:239 soluble molecules 223:239 soluble molecules 223:239 They occur as soluble molecules, or form proteoglycans by being O-linked to different core proteins on the cell surface and in the extracellular matrix. 26970331 7 62 theme plasma 1099:1104 arg1 proteins 1106:1113 plasma proteins 1099:1113 plasma proteins 1099:1113 Four hundred and fifty eight human GAG binding proteins have been identified, whereas plasma proteins showed clear differences in their GAG-binding specificity/selectivity and affinity. 26970331 5 63 theme binding 667:673 arg1 proteome 675:682 the human GAG binding proteome 653:682 the human GAG binding proteome of different sources 653:703 The aim of this study was therefore to investigate the human GAG binding proteome of different sources by using the major GAG classes as ligands, and to explore the GAG-binding selectivity of the human plasma proteome. 26970331 12 64 theme human 1811:1815 arg1 subproteomes 1817:1828 human subproteomes 1811:1828 human subproteomes 1811:1828 The method described here is well suited for identifying GAG-binding proteins and for comparing human subproteomes with respect to binding to different GAG classes. 26970331 12 65 dep suited 1749:1754 arg1 comparing 1801:1809 comparing 1801:1809 comparing human subproteomes with respect to binding to different GAG classes 1801:1877 The method described here is well suited for identifying GAG-binding proteins and for comparing human subproteomes with respect to binding to different GAG classes. 26970331 12 65 dep suited 1749:1754 arg1 identifying 1760:1770 identifying 1760:1770 identifying GAG-binding proteins 1760:1791 The method described here is well suited for identifying GAG-binding proteins and for comparing human subproteomes with respect to binding to different GAG classes. 26970331 7 66 theme GAG 1048:1050 arg1 proteins 1060:1067 Four hundred and fifty eight human GAG binding proteins 1013:1067 Four hundred and fifty eight human GAG binding proteins 1013:1067 Four hundred and fifty eight human GAG binding proteins have been identified, whereas plasma proteins showed clear differences in their GAG-binding specificity/selectivity and affinity. 26970331 5 67 theme GAG 724:726 arg1 classes 728:734 the major GAG classes 714:734 the major GAG classes as ligands 714:745 The aim of this study was therefore to investigate the human GAG binding proteome of different sources by using the major GAG classes as ligands, and to explore the GAG-binding selectivity of the human plasma proteome. 26970331 2 68 from proteins 300:307 arg1 matrix 354:359 the extracellular matrix 336:359 the extracellular matrix 336:359 They occur as soluble molecules, or form proteoglycans by being O-linked to different core proteins on the cell surface and in the extracellular matrix. 26970331 2 68 from proteins 300:307 arg1 surface 321:327 the cell surface 312:327 the cell surface 312:327 They occur as soluble molecules, or form proteoglycans by being O-linked to different core proteins on the cell surface and in the extracellular matrix. 26970331 9 69 theme step-gradient 1368:1380 arg1 elution 1387:1393 step-gradient salt elution 1368:1393 step-gradient salt elution 1368:1393 Moreover, step-gradient salt elution revealed different binding affinities toward different GAG ligands. 26970331 3 70 theme diverse 400:406 arg1 proteins 408:415 diverse proteins 400:415 diverse proteins 400:415 Due to their ability to interact with diverse proteins and to modulate their biologic functions, GAGs are main drivers of mammalian biology. 26970331 6 71 theme low 882:884 arg1 heparin 903:909 immobilized low molecular weight heparin 870:909 immobilized low molecular weight heparin 870:909 For this purpose, proteins were pulled down from immobilized low molecular weight heparin, heparan sulfate, and dermatan sulfate under different conditions and were identified by nano-LC/MS². 26970331 11 72 theme proteins 1622:1629 arg1 annotation 1581:1590 Functional annotation 1570:1590 Functional annotation of the identified GAG-binding proteins 1570:1629 Functional annotation of the identified GAG-binding proteins showed clusters of proteins that are involved in a variety of biological processes. 26970331 1 73 dep linear 131:136 arg1 sulfated 146:153 sulfated 146:153 sulfated 146:153 Glycosaminoglycans (GAGs) are linear, highly sulfated polysaccharides expressed by almost all animal cells. 26970331 3 74 theme biology 494:500 arg1 GAGs 459:462 GAGs 459:462 GAGs 459:462 Due to their ability to interact with diverse proteins and to modulate their biologic functions, GAGs are main drivers of mammalian biology. 26970331 3 74 theme biology 494:500 arg1 drivers 473:479 main drivers 468:479 main drivers of mammalian biology 468:500 Due to their ability to interact with diverse proteins and to modulate their biologic functions, GAGs are main drivers of mammalian biology. 26970331 9 75 theme salt 1382:1385 arg1 elution 1387:1393 step-gradient salt elution 1368:1393 step-gradient salt elution 1368:1393 Moreover, step-gradient salt elution revealed different binding affinities toward different GAG ligands. 26019041 10 0 theme iron 1136:1139 arg1 levels 1126:1131 no increased levels 1113:1131 no increased levels of iron in the liver 1113:1152 There were no increased levels of iron in the liver. 26019041 8 1 theme steatosis 951:959 arg1 grade 942:946 the highest grade 930:946 the highest grade of steatosis (grade 2 of 3) and HSD 930:982 RESULTS The HFC diet had the highest grade of steatosis (grade 2 of 3) and HSD showed also steatosis (grade 1). 26019041 4 2 theme 5 563:563 arg1 % 564:564 % 564:564 % 564:564 MATERIAL AND METHODS Eight week-old male Wistar rats were divided in four groups and fed for 90 days with the following diets: 1) Control chow diet (C); 2) High-fat cholesterol diet (HFC) + 5% sucrose in drinking water. 26019041 14 3 theme HFCO 1348:1351 arg1 diets 1353:1357 The HSD and the HFCO diets 1332:1357 The HSD and the HFCO diets 1332:1357 The HSD and the HFCO diets developed also hyperglycemia. 26019041 17 4 theme sucrose 1563:1569 arg1 combination 1530:1540 combination 1530:1540 combination of high fat and high sucrose 1530:1569 In conclusion, the HFC diet with combination of high fat and high sucrose is more effective in producing NAFLD compared with a high sucrose diet only. 26019041 3 5 theme diets 262:266 arg1 impact 240:245 the impact 236:245 the impact of 4 different diets in the production of NAFLD 236:293 AIM Evaluate the impact of 4 different diets in the production of NAFLD with emphasis on a combined high-fat plus sustained high sucrose consumption. 26019041 2 6 theme disease 201:207 arg1 pathogenesis 209:220 disease pathogenesis 201:220 disease pathogenesis 201:220 Using murine models helps to understand disease pathogenesis. 26019041 8 7 dep RESULTS 905:911 arg1 had 926:928 had 926:928 had the highest grade of steatosis (grade 2 of 3) and HSD 926:982 RESULTS The HFC diet had the highest grade of steatosis (grade 2 of 3) and HSD showed also steatosis (grade 1). 26019041 8 8 theme HSD 980:982 arg1 grade 942:946 the highest grade 930:946 the highest grade of steatosis (grade 2 of 3) and HSD 930:982 RESULTS The HFC diet had the highest grade of steatosis (grade 2 of 3) and HSD showed also steatosis (grade 1). 26019041 5 9 theme cornstarch 605:614 arg1 HFCO 622:625 HFCO 622:625 HFCO 622:625 3) High-fat cornstarch diet (HFCO) + 5% sucrose in drinking water. 26019041 5 9 theme cornstarch 605:614 arg1 diet 616:619 3) High-fat cornstarch diet 593:619 3) High-fat cornstarch diet (HFCO) 593:626 3) High-fat cornstarch diet (HFCO) + 5% sucrose in drinking water. 26019041 9 10 from TG 1030:1031 arg1 liver 1066:1070 liver 1066:1070 liver 1066:1070 Liver weight TG and colesterol concentrations in liver were greater in the HFC diet. 26019041 17 11 theme high 1624:1627 arg1 diet 1637:1640 a high sucrose diet 1622:1640 a high sucrose diet only 1622:1645 In conclusion, the HFC diet with combination of high fat and high sucrose is more effective in producing NAFLD compared with a high sucrose diet only. 26019041 13 12 theme highest 1279:1285 arg1 < 1322:1322 P < 0.005 1320:1328 P < 0.005 1320:1328 HFC had the highest glucose level (158.5 ± 7 mg/dL) (P < 0.005). 26019041 13 12 theme highest 1279:1285 arg1 mg/dL 1312:1316 158.5 ± 7 mg/dL 1302:1316 158.5 ± 7 mg/dL 1302:1316 HFC had the highest glucose level (158.5 ± 7 mg/dL) (P < 0.005). 26019041 13 12 theme highest 1279:1285 arg1 level 1295:1299 the highest glucose level 1275:1299 the highest glucose level (158.5 ± 7 mg/dL) (P < 0.005) 1275:1329 HFC had the highest glucose level (158.5 ± 7 mg/dL) (P < 0.005). 26019041 7 13 theme liver 746:750 arg1 histology 752:760 liver histology 746:760 liver histology 746:760 Metabolic changes, leptin levels, liver histology, hepatic and plasma lipid composition, fasting plasma glucose and insulin and liver gene expression of FAS, SREBP-1 and PPAR-α were evaluated. 26019041 4 14 theme week-old 400:407 arg1 rats 421:424 Eight week-old male Wistar rats 394:424 Eight week-old male Wistar rats 394:424 MATERIAL AND METHODS Eight week-old male Wistar rats were divided in four groups and fed for 90 days with the following diets: 1) Control chow diet (C); 2) High-fat cholesterol diet (HFC) + 5% sucrose in drinking water. 26019041 7 15 theme gene 846:849 arg1 expression 851:860 liver gene expression 840:860 liver gene expression of FAS, SREBP-1 and PPAR-α 840:887 Metabolic changes, leptin levels, liver histology, hepatic and plasma lipid composition, fasting plasma glucose and insulin and liver gene expression of FAS, SREBP-1 and PPAR-α were evaluated. 26019041 9 16 theme Liver 1017:1021 arg1 TG 1030:1031 Liver weight TG and colesterol concentrations 1017:1061 TG 1030:1031 Liver weight TG and colesterol concentrations in liver were greater in the HFC diet. 26019041 7 17 theme fasting 801:807 arg1 glucose 816:822 fasting plasma glucose 801:822 fasting plasma glucose 801:822 Metabolic changes, leptin levels, liver histology, hepatic and plasma lipid composition, fasting plasma glucose and insulin and liver gene expression of FAS, SREBP-1 and PPAR-α were evaluated. 26019041 1 18 theme NAFLD 120:124 arg1 study 111:115 The study 107:115 The study of NAFLD in humans 107:134 BACKGROUND The study of NAFLD in humans has several limitations. 26019041 4 19 theme Wistar 414:419 arg1 rats 421:424 Eight week-old male Wistar rats 394:424 Eight week-old male Wistar rats 394:424 MATERIAL AND METHODS Eight week-old male Wistar rats were divided in four groups and fed for 90 days with the following diets: 1) Control chow diet (C); 2) High-fat cholesterol diet (HFC) + 5% sucrose in drinking water. 26019041 4 20 theme drinking 577:584 arg1 water 586:590 drinking water 577:590 drinking water 577:590 MATERIAL AND METHODS Eight week-old male Wistar rats were divided in four groups and fed for 90 days with the following diets: 1) Control chow diet (C); 2) High-fat cholesterol diet (HFC) + 5% sucrose in drinking water. 26019041 5 21 theme 5 630:630 arg1 % 631:631 % 631:631 % 631:631 3) High-fat cornstarch diet (HFCO) + 5% sucrose in drinking water. 26019041 14 22 theme HSD 1336:1338 arg1 diets 1353:1357 The HSD and the HFCO diets 1332:1357 The HSD and the HFCO diets 1332:1357 The HSD and the HFCO diets developed also hyperglycemia. 26019041 3 23 from impact 240:245 arg1 production 275:284 the production 271:284 the production of NAFLD 271:293 AIM Evaluate the impact of 4 different diets in the production of NAFLD with emphasis on a combined high-fat plus sustained high sucrose consumption. 26019041 15 24 theme higher 1411:1416 arg1 hyperinsulinemia 1426:1441 significantly higher fasting hyperinsulinemia 1397:1441 significantly higher fasting hyperinsulinemia 1397:1441 HSD had significantly higher fasting hyperinsulinemia. 26019041 9 25 theme colesterol 1037:1046 arg1 concentrations 1048:1061 Liver weight TG and colesterol concentrations 1017:1061 concentrations 1048:1061 Liver weight TG and colesterol concentrations in liver were greater in the HFC diet. 26019041 17 26 theme HFC 1516:1518 arg1 diet 1520:1523 the HFC diet 1512:1523 the HFC diet with combination of high fat and high sucrose 1512:1569 In conclusion, the HFC diet with combination of high fat and high sucrose is more effective in producing NAFLD compared with a high sucrose diet only. 26019041 17 26 theme HFC 1516:1518 arg1 effective 1579:1587 effective 1579:1587 effective 1579:1587 In conclusion, the HFC diet with combination of high fat and high sucrose is more effective in producing NAFLD compared with a high sucrose diet only. 26019041 7 27 theme plasma 775:780 arg1 composition 788:798 plasma lipid composition 775:798 plasma lipid composition 775:798 Metabolic changes, leptin levels, liver histology, hepatic and plasma lipid composition, fasting plasma glucose and insulin and liver gene expression of FAS, SREBP-1 and PPAR-α were evaluated. 26019041 1 28 theme several 140:146 arg1 limitations 148:158 several limitations 140:158 several limitations 140:158 BACKGROUND The study of NAFLD in humans has several limitations. 26019041 8 29 dep steatosis 951:959 arg1 grade 962:966 grade 2 962:968 grade 2 of 3 962:973 RESULTS The HFC diet had the highest grade of steatosis (grade 2 of 3) and HSD showed also steatosis (grade 1). 26019041 4 30 dep MATERIAL 373:380 arg1 rats 421:424 Eight week-old male Wistar rats 394:424 Eight week-old male Wistar rats 394:424 MATERIAL AND METHODS Eight week-old male Wistar rats were divided in four groups and fed for 90 days with the following diets: 1) Control chow diet (C); 2) High-fat cholesterol diet (HFC) + 5% sucrose in drinking water. 26019041 0 31 theme murine 82:87 arg1 model 89:93 a murine model 80:93 a murine model 80:93 Combined high-fat diet and sustained high sucrose consumption promotes NAFLD in a murine model. 26019041 4 32 dep diet 516:519 arg1 HFC 556:558 HFC 556:558 HFC 556:558 MATERIAL AND METHODS Eight week-old male Wistar rats were divided in four groups and fed for 90 days with the following diets: 1) Control chow diet (C); 2) High-fat cholesterol diet (HFC) + 5% sucrose in drinking water. 26019041 4 32 dep diet 516:519 arg1 diet 550:553 High-fat cholesterol diet 529:553 High-fat cholesterol diet (HFC) 529:559 MATERIAL AND METHODS Eight week-old male Wistar rats were divided in four groups and fed for 90 days with the following diets: 1) Control chow diet (C); 2) High-fat cholesterol diet (HFC) + 5% sucrose in drinking water. 26019041 4 32 dep diet 516:519 arg1 1 500:500 1 500:500 1 500:500 MATERIAL AND METHODS Eight week-old male Wistar rats were divided in four groups and fed for 90 days with the following diets: 1) Control chow diet (C); 2) High-fat cholesterol diet (HFC) + 5% sucrose in drinking water. 26019041 4 32 dep diet 516:519 arg1 sucrose 566:572 5% sucrose 563:572 5% sucrose 563:572 MATERIAL AND METHODS Eight week-old male Wistar rats were divided in four groups and fed for 90 days with the following diets: 1) Control chow diet (C); 2) High-fat cholesterol diet (HFC) + 5% sucrose in drinking water. 26019041 3 33 theme combined 314:321 arg1 high-fat 323:330 a combined high-fat 312:330 a combined high-fat 312:330 AIM Evaluate the impact of 4 different diets in the production of NAFLD with emphasis on a combined high-fat plus sustained high sucrose consumption. 26019041 15 34 theme fasting 1418:1424 arg1 hyperinsulinemia 1426:1441 significantly higher fasting hyperinsulinemia 1397:1441 significantly higher fasting hyperinsulinemia 1397:1441 HSD had significantly higher fasting hyperinsulinemia. 26019041 0 35 theme Combined 0:7 arg1 diet 18:21 Combined high-fat diet 0:21 Combined high-fat diet 0:21 Combined high-fat diet and sustained high sucrose consumption promotes NAFLD in a murine model. 26019041 17 36 theme fat 1550:1552 arg1 combination 1530:1540 combination 1530:1540 combination of high fat and high sucrose 1530:1569 In conclusion, the HFC diet with combination of high fat and high sucrose is more effective in producing NAFLD compared with a high sucrose diet only. 26019041 3 37 theme high 347:350 arg1 consumption 360:370 sustained high sucrose consumption 337:370 sustained high sucrose consumption 337:370 AIM Evaluate the impact of 4 different diets in the production of NAFLD with emphasis on a combined high-fat plus sustained high sucrose consumption. 26019041 9 38 theme HFC 1092:1094 arg1 diet 1096:1099 the HFC diet 1088:1099 the HFC diet 1088:1099 Liver weight TG and colesterol concentrations in liver were greater in the HFC diet. 26019041 17 39 with diet 1520:1523 arg1 combination 1530:1540 combination 1530:1540 combination of high fat and high sucrose 1530:1569 In conclusion, the HFC diet with combination of high fat and high sucrose is more effective in producing NAFLD compared with a high sucrose diet only. 26019041 4 40 theme chow 511:514 arg1 C 522:522 C 522:522 C 522:522 MATERIAL AND METHODS Eight week-old male Wistar rats were divided in four groups and fed for 90 days with the following diets: 1) Control chow diet (C); 2) High-fat cholesterol diet (HFC) + 5% sucrose in drinking water. 26019041 4 40 theme chow 511:514 arg1 diet 516:519 Control chow diet 503:519 1) Control chow diet (C); 2) High-fat cholesterol diet (HFC) + 5% sucrose in drinking water 500:590 MATERIAL AND METHODS Eight week-old male Wistar rats were divided in four groups and fed for 90 days with the following diets: 1) Control chow diet (C); 2) High-fat cholesterol diet (HFC) + 5% sucrose in drinking water. 26019041 11 41 theme more 1188:1191 arg1 weight 1193:1198 significantly more weight 1174:1198 significantly more weight (P < 0.001) 1174:1210 Rats in HFC gained significantly more weight (P < 0.001). 26019041 11 41 theme more 1188:1191 arg1 < 1203:1203 P < 0.001 1201:1209 P < 0.001 1201:1209 Rats in HFC gained significantly more weight (P < 0.001). 26019041 16 42 theme HFC 1475:1477 arg1 diet 1479:1482 the HFC diet 1471:1482 the HFC diet 1471:1482 Serum leptin was higher in the HFC diet (p = 0.001). 26019041 4 43 theme following 483:491 arg1 diets 493:497 the following diets 479:497 the following diets 479:497 MATERIAL AND METHODS Eight week-old male Wistar rats were divided in four groups and fed for 90 days with the following diets: 1) Control chow diet (C); 2) High-fat cholesterol diet (HFC) + 5% sucrose in drinking water. 26019041 0 44 theme sucrose 42:48 arg1 consumption 50:60 sustained high sucrose consumption 27:60 sustained high sucrose consumption 27:60 Combined high-fat diet and sustained high sucrose consumption promotes NAFLD in a murine model. 26019041 4 45 dep diet 550:553 arg1 2 526:526 2 526:526 2 526:526 MATERIAL AND METHODS Eight week-old male Wistar rats were divided in four groups and fed for 90 days with the following diets: 1) Control chow diet (C); 2) High-fat cholesterol diet (HFC) + 5% sucrose in drinking water. 26019041 17 46 from conclusion 1500:1509 arg1 diet 1520:1523 the HFC diet 1512:1523 the HFC diet with combination of high fat and high sucrose 1512:1569 In conclusion, the HFC diet with combination of high fat and high sucrose is more effective in producing NAFLD compared with a high sucrose diet only. 26019041 17 46 from conclusion 1500:1509 arg1 effective 1579:1587 effective 1579:1587 effective 1579:1587 In conclusion, the HFC diet with combination of high fat and high sucrose is more effective in producing NAFLD compared with a high sucrose diet only. 26019041 8 47 theme HFC 917:919 arg1 diet 921:924 The HFC diet 913:924 The HFC diet 913:924 RESULTS The HFC diet had the highest grade of steatosis (grade 2 of 3) and HSD showed also steatosis (grade 1). 26019041 6 48 theme 20 675:676 arg1 % 677:677 % 677:677 % 677:677 4) Chow diet + 20% sucrose in drinking water (HSD). 26019041 4 49 theme High-fat 529:536 arg1 HFC 556:558 HFC 556:558 HFC 556:558 MATERIAL AND METHODS Eight week-old male Wistar rats were divided in four groups and fed for 90 days with the following diets: 1) Control chow diet (C); 2) High-fat cholesterol diet (HFC) + 5% sucrose in drinking water. 26019041 4 49 theme High-fat 529:536 arg1 diet 550:553 High-fat cholesterol diet 529:553 High-fat cholesterol diet (HFC) 529:559 MATERIAL AND METHODS Eight week-old male Wistar rats were divided in four groups and fed for 90 days with the following diets: 1) Control chow diet (C); 2) High-fat cholesterol diet (HFC) + 5% sucrose in drinking water. 26019041 13 50 contain had 1271:1273 arg2 mg/dL 1312:1316 158.5 ± 7 mg/dL 1302:1316 158.5 ± 7 mg/dL 1302:1316 HFC had the highest glucose level (158.5 ± 7 mg/dL) (P < 0.005). 26019041 13 50 contain had 1271:1273 arg2 level 1295:1299 the highest glucose level 1275:1299 the highest glucose level (158.5 ± 7 mg/dL) (P < 0.005) 1275:1329 HFC had the highest glucose level (158.5 ± 7 mg/dL) (P < 0.005). 26019041 13 50 contain had 1271:1273 arg1 HFC 1267:1269 HFC 1267:1269 HFC 1267:1269 HFC had the highest glucose level (158.5 ± 7 mg/dL) (P < 0.005). 26019041 13 50 contain had 1271:1273 arg2 < 1322:1322 P < 0.005 1320:1328 P < 0.005 1320:1328 HFC had the highest glucose level (158.5 ± 7 mg/dL) (P < 0.005). 26019041 15 51 contain had 1393:1395 arg1 HSD 1389:1391 HSD 1389:1391 HSD 1389:1391 HSD had significantly higher fasting hyperinsulinemia. 26019041 15 51 contain had 1393:1395 arg2 hyperinsulinemia 1426:1441 significantly higher fasting hyperinsulinemia 1397:1441 significantly higher fasting hyperinsulinemia 1397:1441 HSD had significantly higher fasting hyperinsulinemia. 26019041 7 52 theme Metabolic 712:720 arg1 changes 722:728 Metabolic changes 712:728 Metabolic changes 712:728 Metabolic changes, leptin levels, liver histology, hepatic and plasma lipid composition, fasting plasma glucose and insulin and liver gene expression of FAS, SREBP-1 and PPAR-α were evaluated. 26019041 8 53 theme highest 934:940 arg1 grade 942:946 the highest grade 930:946 the highest grade of steatosis (grade 2 of 3) and HSD 930:982 RESULTS The HFC diet had the highest grade of steatosis (grade 2 of 3) and HSD showed also steatosis (grade 1). 26019041 6 54 theme Chow 663:666 arg1 diet 668:671 Chow diet 663:671 Chow diet 663:671 4) Chow diet + 20% sucrose in drinking water (HSD). 26019041 13 55 theme ± 1308:1308 arg1 mg/dL 1312:1316 158.5 ± 7 mg/dL 1302:1316 158.5 ± 7 mg/dL 1302:1316 HFC had the highest glucose level (158.5 ± 7 mg/dL) (P < 0.005). 26019041 13 55 theme ± 1308:1308 arg1 level 1295:1299 the highest glucose level 1275:1299 the highest glucose level (158.5 ± 7 mg/dL) (P < 0.005) 1275:1329 HFC had the highest glucose level (158.5 ± 7 mg/dL) (P < 0.005). 26019041 16 56 theme Serum 1444:1448 arg1 leptin 1450:1455 Serum leptin 1444:1455 Serum leptin 1444:1455 Serum leptin was higher in the HFC diet (p = 0.001). 26019041 17 57 theme sucrose 1629:1635 arg1 diet 1637:1640 a high sucrose diet 1622:1640 a high sucrose diet only 1622:1645 In conclusion, the HFC diet with combination of high fat and high sucrose is more effective in producing NAFLD compared with a high sucrose diet only. 26019041 1 58 contain has 136:138 arg2 limitations 148:158 several limitations 140:158 several limitations 140:158 BACKGROUND The study of NAFLD in humans has several limitations. 26019041 1 58 contain has 136:138 arg1 study 111:115 The study 107:115 The study of NAFLD in humans 107:134 BACKGROUND The study of NAFLD in humans has several limitations. 26019041 10 59 theme increased 1116:1124 arg1 levels 1126:1131 no increased levels 1113:1131 no increased levels of iron in the liver 1113:1152 There were no increased levels of iron in the liver. 26019041 7 60 theme PPAR-α 882:887 arg1 levels 738:743 leptin levels 731:743 leptin levels 731:743 Metabolic changes, leptin levels, liver histology, hepatic and plasma lipid composition, fasting plasma glucose and insulin and liver gene expression of FAS, SREBP-1 and PPAR-α were evaluated. 26019041 7 60 theme PPAR-α 882:887 arg1 expression 851:860 liver gene expression 840:860 liver gene expression of FAS, SREBP-1 and PPAR-α 840:887 Metabolic changes, leptin levels, liver histology, hepatic and plasma lipid composition, fasting plasma glucose and insulin and liver gene expression of FAS, SREBP-1 and PPAR-α were evaluated. 26019041 7 60 theme PPAR-α 882:887 arg1 glucose 816:822 fasting plasma glucose 801:822 fasting plasma glucose 801:822 Metabolic changes, leptin levels, liver histology, hepatic and plasma lipid composition, fasting plasma glucose and insulin and liver gene expression of FAS, SREBP-1 and PPAR-α were evaluated. 26019041 7 60 theme PPAR-α 882:887 arg1 insulin 828:834 insulin 828:834 insulin 828:834 Metabolic changes, leptin levels, liver histology, hepatic and plasma lipid composition, fasting plasma glucose and insulin and liver gene expression of FAS, SREBP-1 and PPAR-α were evaluated. 26019041 7 60 theme PPAR-α 882:887 arg1 histology 752:760 liver histology 746:760 liver histology 746:760 Metabolic changes, leptin levels, liver histology, hepatic and plasma lipid composition, fasting plasma glucose and insulin and liver gene expression of FAS, SREBP-1 and PPAR-α were evaluated. 26019041 7 60 theme PPAR-α 882:887 arg1 composition 788:798 plasma lipid composition 775:798 plasma lipid composition 775:798 Metabolic changes, leptin levels, liver histology, hepatic and plasma lipid composition, fasting plasma glucose and insulin and liver gene expression of FAS, SREBP-1 and PPAR-α were evaluated. 26019041 7 60 theme PPAR-α 882:887 arg1 changes 722:728 Metabolic changes 712:728 Metabolic changes 712:728 Metabolic changes, leptin levels, liver histology, hepatic and plasma lipid composition, fasting plasma glucose and insulin and liver gene expression of FAS, SREBP-1 and PPAR-α were evaluated. 26019041 13 61 theme glucose 1287:1293 arg1 < 1322:1322 P < 0.005 1320:1328 P < 0.005 1320:1328 HFC had the highest glucose level (158.5 ± 7 mg/dL) (P < 0.005). 26019041 13 61 theme glucose 1287:1293 arg1 mg/dL 1312:1316 158.5 ± 7 mg/dL 1302:1316 158.5 ± 7 mg/dL 1302:1316 HFC had the highest glucose level (158.5 ± 7 mg/dL) (P < 0.005). 26019041 13 61 theme glucose 1287:1293 arg1 level 1295:1299 the highest glucose level 1275:1299 the highest glucose level (158.5 ± 7 mg/dL) (P < 0.005) 1275:1329 HFC had the highest glucose level (158.5 ± 7 mg/dL) (P < 0.005). 26019041 17 62 theme high 1558:1561 arg1 sucrose 1563:1569 high sucrose 1558:1569 high sucrose 1558:1569 In conclusion, the HFC diet with combination of high fat and high sucrose is more effective in producing NAFLD compared with a high sucrose diet only. 26019041 4 63 theme % 564:564 arg1 sucrose 566:572 5% sucrose 563:572 5% sucrose 563:572 MATERIAL AND METHODS Eight week-old male Wistar rats were divided in four groups and fed for 90 days with the following diets: 1) Control chow diet (C); 2) High-fat cholesterol diet (HFC) + 5% sucrose in drinking water. 26019041 7 64 theme SREBP-1 870:876 arg1 levels 738:743 leptin levels 731:743 leptin levels 731:743 Metabolic changes, leptin levels, liver histology, hepatic and plasma lipid composition, fasting plasma glucose and insulin and liver gene expression of FAS, SREBP-1 and PPAR-α were evaluated. 26019041 7 64 theme SREBP-1 870:876 arg1 expression 851:860 liver gene expression 840:860 liver gene expression of FAS, SREBP-1 and PPAR-α 840:887 Metabolic changes, leptin levels, liver histology, hepatic and plasma lipid composition, fasting plasma glucose and insulin and liver gene expression of FAS, SREBP-1 and PPAR-α were evaluated. 26019041 7 64 theme SREBP-1 870:876 arg1 glucose 816:822 fasting plasma glucose 801:822 fasting plasma glucose 801:822 Metabolic changes, leptin levels, liver histology, hepatic and plasma lipid composition, fasting plasma glucose and insulin and liver gene expression of FAS, SREBP-1 and PPAR-α were evaluated. 26019041 7 64 theme SREBP-1 870:876 arg1 insulin 828:834 insulin 828:834 insulin 828:834 Metabolic changes, leptin levels, liver histology, hepatic and plasma lipid composition, fasting plasma glucose and insulin and liver gene expression of FAS, SREBP-1 and PPAR-α were evaluated. 26019041 7 64 theme SREBP-1 870:876 arg1 histology 752:760 liver histology 746:760 liver histology 746:760 Metabolic changes, leptin levels, liver histology, hepatic and plasma lipid composition, fasting plasma glucose and insulin and liver gene expression of FAS, SREBP-1 and PPAR-α were evaluated. 26019041 7 64 theme SREBP-1 870:876 arg1 composition 788:798 plasma lipid composition 775:798 plasma lipid composition 775:798 Metabolic changes, leptin levels, liver histology, hepatic and plasma lipid composition, fasting plasma glucose and insulin and liver gene expression of FAS, SREBP-1 and PPAR-α were evaluated. 26019041 7 64 theme SREBP-1 870:876 arg1 changes 722:728 Metabolic changes 712:728 Metabolic changes 712:728 Metabolic changes, leptin levels, liver histology, hepatic and plasma lipid composition, fasting plasma glucose and insulin and liver gene expression of FAS, SREBP-1 and PPAR-α were evaluated. 26019041 8 65 contain had 926:928 arg2 grade 942:946 the highest grade 930:946 the highest grade of steatosis (grade 2 of 3) and HSD 930:982 RESULTS The HFC diet had the highest grade of steatosis (grade 2 of 3) and HSD showed also steatosis (grade 1). 26019041 8 65 contain had 926:928 arg1 diet 921:924 The HFC diet 913:924 The HFC diet 913:924 RESULTS The HFC diet had the highest grade of steatosis (grade 2 of 3) and HSD showed also steatosis (grade 1). 26019041 8 66 theme 3 973:973 arg1 grade 962:966 grade 2 962:968 grade 2 of 3 962:973 RESULTS The HFC diet had the highest grade of steatosis (grade 2 of 3) and HSD showed also steatosis (grade 1). 26019041 6 67 dep diet 668:671 arg1 4 660:660 4 660:660 4 660:660 4) Chow diet + 20% sucrose in drinking water (HSD). 26019041 5 68 theme High-fat 596:603 arg1 HFCO 622:625 HFCO 622:625 HFCO 622:625 3) High-fat cornstarch diet (HFCO) + 5% sucrose in drinking water. 26019041 5 68 theme High-fat 596:603 arg1 diet 616:619 3) High-fat cornstarch diet 593:619 3) High-fat cornstarch diet (HFCO) 593:626 3) High-fat cornstarch diet (HFCO) + 5% sucrose in drinking water. 26019041 4 69 from diet 550:553 arg1 water 586:590 drinking water 577:590 drinking water 577:590 MATERIAL AND METHODS Eight week-old male Wistar rats were divided in four groups and fed for 90 days with the following diets: 1) Control chow diet (C); 2) High-fat cholesterol diet (HFC) + 5% sucrose in drinking water. 26019041 9 70 from concentrations 1048:1061 arg1 liver 1066:1070 liver 1066:1070 liver 1066:1070 Liver weight TG and colesterol concentrations in liver were greater in the HFC diet. 26019041 3 71 theme different 252:260 arg1 diets 262:266 4 different diets 250:266 4 different diets 250:266 AIM Evaluate the impact of 4 different diets in the production of NAFLD with emphasis on a combined high-fat plus sustained high sucrose consumption. 26019041 0 72 from NAFLD 71:75 arg1 model 89:93 a murine model 80:93 a murine model 80:93 Combined high-fat diet and sustained high sucrose consumption promotes NAFLD in a murine model. 26019041 3 73 theme NAFLD 289:293 arg1 production 275:284 the production 271:284 the production of NAFLD 271:293 AIM Evaluate the impact of 4 different diets in the production of NAFLD with emphasis on a combined high-fat plus sustained high sucrose consumption. 26019041 4 74 theme male 409:412 arg1 rats 421:424 Eight week-old male Wistar rats 394:424 Eight week-old male Wistar rats 394:424 MATERIAL AND METHODS Eight week-old male Wistar rats were divided in four groups and fed for 90 days with the following diets: 1) Control chow diet (C); 2) High-fat cholesterol diet (HFC) + 5% sucrose in drinking water. 26019041 7 75 theme liver 840:844 arg1 expression 851:860 liver gene expression 840:860 liver gene expression of FAS, SREBP-1 and PPAR-α 840:887 Metabolic changes, leptin levels, liver histology, hepatic and plasma lipid composition, fasting plasma glucose and insulin and liver gene expression of FAS, SREBP-1 and PPAR-α were evaluated. 26019041 3 76 from emphasis 300:307 arg1 consumption 360:370 sustained high sucrose consumption 337:370 sustained high sucrose consumption 337:370 AIM Evaluate the impact of 4 different diets in the production of NAFLD with emphasis on a combined high-fat plus sustained high sucrose consumption. 26019041 3 76 from emphasis 300:307 arg1 high-fat 323:330 a combined high-fat 312:330 a combined high-fat 312:330 AIM Evaluate the impact of 4 different diets in the production of NAFLD with emphasis on a combined high-fat plus sustained high sucrose consumption. 26019041 0 77 from model 89:93 arg1 NAFLD 71:75 NAFLD 71:75 NAFLD 71:75 Combined high-fat diet and sustained high sucrose consumption promotes NAFLD in a murine model. 26019041 11 78 theme P 1201:1201 arg1 weight 1193:1198 significantly more weight 1174:1198 significantly more weight (P < 0.001) 1174:1210 Rats in HFC gained significantly more weight (P < 0.001). 26019041 11 78 theme P 1201:1201 arg1 < 1203:1203 P < 0.001 1201:1209 P < 0.001 1201:1209 Rats in HFC gained significantly more weight (P < 0.001). 26019041 9 79 theme weight 1023:1028 arg1 TG 1030:1031 Liver weight TG and colesterol concentrations 1017:1061 TG 1030:1031 Liver weight TG and colesterol concentrations in liver were greater in the HFC diet. 26019041 7 80 theme plasma 809:814 arg1 glucose 816:822 fasting plasma glucose 801:822 fasting plasma glucose 801:822 Metabolic changes, leptin levels, liver histology, hepatic and plasma lipid composition, fasting plasma glucose and insulin and liver gene expression of FAS, SREBP-1 and PPAR-α were evaluated. 26019041 1 81 dep BACKGROUND 96:105 arg1 has 136:138 has 136:138 has several limitations 136:158 BACKGROUND The study of NAFLD in humans has several limitations. 26019041 5 82 theme % 631:631 arg1 sucrose 633:639 5% sucrose 630:639 5% sucrose 630:639 3) High-fat cornstarch diet (HFCO) + 5% sucrose in drinking water. 26019041 12 83 theme fasting 1244:1250 arg1 hyperglycemia 1252:1264 fasting hyperglycemia 1244:1264 fasting hyperglycemia 1244:1264 All experimental groups showed fasting hyperglycemia. 26019041 17 84 from effective 1579:1587 arg1 conclusion 1500:1509 conclusion 1500:1509 conclusion 1500:1509 In conclusion, the HFC diet with combination of high fat and high sucrose is more effective in producing NAFLD compared with a high sucrose diet only. 26019041 7 85 theme lipid 782:786 arg1 composition 788:798 plasma lipid composition 775:798 plasma lipid composition 775:798 Metabolic changes, leptin levels, liver histology, hepatic and plasma lipid composition, fasting plasma glucose and insulin and liver gene expression of FAS, SREBP-1 and PPAR-α were evaluated. 26019041 0 86 theme high-fat 9:16 arg1 diet 18:21 Combined high-fat diet 0:21 Combined high-fat diet 0:21 Combined high-fat diet and sustained high sucrose consumption promotes NAFLD in a murine model. 26019041 17 87 theme high 1545:1548 arg1 fat 1550:1552 high fat 1545:1552 high fat 1545:1552 In conclusion, the HFC diet with combination of high fat and high sucrose is more effective in producing NAFLD compared with a high sucrose diet only. 26019041 7 88 theme FAS 865:867 arg1 levels 738:743 leptin levels 731:743 leptin levels 731:743 Metabolic changes, leptin levels, liver histology, hepatic and plasma lipid composition, fasting plasma glucose and insulin and liver gene expression of FAS, SREBP-1 and PPAR-α were evaluated. 26019041 7 88 theme FAS 865:867 arg1 expression 851:860 liver gene expression 840:860 liver gene expression of FAS, SREBP-1 and PPAR-α 840:887 Metabolic changes, leptin levels, liver histology, hepatic and plasma lipid composition, fasting plasma glucose and insulin and liver gene expression of FAS, SREBP-1 and PPAR-α were evaluated. 26019041 7 88 theme FAS 865:867 arg1 glucose 816:822 fasting plasma glucose 801:822 fasting plasma glucose 801:822 Metabolic changes, leptin levels, liver histology, hepatic and plasma lipid composition, fasting plasma glucose and insulin and liver gene expression of FAS, SREBP-1 and PPAR-α were evaluated. 26019041 7 88 theme FAS 865:867 arg1 insulin 828:834 insulin 828:834 insulin 828:834 Metabolic changes, leptin levels, liver histology, hepatic and plasma lipid composition, fasting plasma glucose and insulin and liver gene expression of FAS, SREBP-1 and PPAR-α were evaluated. 26019041 7 88 theme FAS 865:867 arg1 histology 752:760 liver histology 746:760 liver histology 746:760 Metabolic changes, leptin levels, liver histology, hepatic and plasma lipid composition, fasting plasma glucose and insulin and liver gene expression of FAS, SREBP-1 and PPAR-α were evaluated. 26019041 7 88 theme FAS 865:867 arg1 composition 788:798 plasma lipid composition 775:798 plasma lipid composition 775:798 Metabolic changes, leptin levels, liver histology, hepatic and plasma lipid composition, fasting plasma glucose and insulin and liver gene expression of FAS, SREBP-1 and PPAR-α were evaluated. 26019041 7 88 theme FAS 865:867 arg1 changes 722:728 Metabolic changes 712:728 Metabolic changes 712:728 Metabolic changes, leptin levels, liver histology, hepatic and plasma lipid composition, fasting plasma glucose and insulin and liver gene expression of FAS, SREBP-1 and PPAR-α were evaluated. 26019041 4 89 theme Control 503:509 arg1 C 522:522 C 522:522 C 522:522 MATERIAL AND METHODS Eight week-old male Wistar rats were divided in four groups and fed for 90 days with the following diets: 1) Control chow diet (C); 2) High-fat cholesterol diet (HFC) + 5% sucrose in drinking water. 26019041 4 89 theme Control 503:509 arg1 diet 516:519 Control chow diet 503:519 1) Control chow diet (C); 2) High-fat cholesterol diet (HFC) + 5% sucrose in drinking water 500:590 MATERIAL AND METHODS Eight week-old male Wistar rats were divided in four groups and fed for 90 days with the following diets: 1) Control chow diet (C); 2) High-fat cholesterol diet (HFC) + 5% sucrose in drinking water. 26019041 1 90 from study 111:115 arg1 humans 129:134 humans 129:134 humans 129:134 BACKGROUND The study of NAFLD in humans has several limitations. 26019041 3 91 theme sucrose 352:358 arg1 consumption 360:370 sustained high sucrose consumption 337:370 sustained high sucrose consumption 337:370 AIM Evaluate the impact of 4 different diets in the production of NAFLD with emphasis on a combined high-fat plus sustained high sucrose consumption. 26019041 2 92 theme murine 167:172 arg1 models 174:179 murine models 167:179 murine models 167:179 Using murine models helps to understand disease pathogenesis. 26019041 0 93 theme high 37:40 arg1 consumption 50:60 sustained high sucrose consumption 27:60 sustained high sucrose consumption 27:60 Combined high-fat diet and sustained high sucrose consumption promotes NAFLD in a murine model. 26019041 12 94 theme experimental 1217:1228 arg1 groups 1230:1235 All experimental groups 1213:1235 All experimental groups 1213:1235 All experimental groups showed fasting hyperglycemia. 26019041 10 95 from levels 1126:1131 arg1 liver 1148:1152 the liver 1144:1152 the liver 1144:1152 There were no increased levels of iron in the liver. 26019041 13 96 theme P 1320:1320 arg1 < 1322:1322 P < 0.005 1320:1328 P < 0.005 1320:1328 HFC had the highest glucose level (158.5 ± 7 mg/dL) (P < 0.005). 26019041 13 96 theme P 1320:1320 arg1 level 1295:1299 the highest glucose level 1275:1299 the highest glucose level (158.5 ± 7 mg/dL) (P < 0.005) 1275:1329 HFC had the highest glucose level (158.5 ± 7 mg/dL) (P < 0.005). 26019041 7 97 theme leptin 731:736 arg1 levels 738:743 leptin levels 731:743 leptin levels 731:743 Metabolic changes, leptin levels, liver histology, hepatic and plasma lipid composition, fasting plasma glucose and insulin and liver gene expression of FAS, SREBP-1 and PPAR-α were evaluated. 26019041 6 98 theme % 677:677 arg1 sucrose 679:685 20% sucrose 675:685 20% sucrose 675:685 4) Chow diet + 20% sucrose in drinking water (HSD). 26019041 11 99 from Rats 1155:1158 arg1 HFC 1163:1165 HFC 1163:1165 HFC 1163:1165 Rats in HFC gained significantly more weight (P < 0.001). 26019041 4 100 theme cholesterol 538:548 arg1 HFC 556:558 HFC 556:558 HFC 556:558 MATERIAL AND METHODS Eight week-old male Wistar rats were divided in four groups and fed for 90 days with the following diets: 1) Control chow diet (C); 2) High-fat cholesterol diet (HFC) + 5% sucrose in drinking water. 26019041 4 100 theme cholesterol 538:548 arg1 diet 550:553 High-fat cholesterol diet 529:553 High-fat cholesterol diet (HFC) 529:559 MATERIAL AND METHODS Eight week-old male Wistar rats were divided in four groups and fed for 90 days with the following diets: 1) Control chow diet (C); 2) High-fat cholesterol diet (HFC) + 5% sucrose in drinking water. 24831678 6 0 theme further 1167:1173 arg1 study 1175:1179 A further study 1165:1179 A further study with this azole 1165:1195 A further study with this azole evidenced the impact of 2,2,6,6-tetramethylpiperidine on the N-arylation yields. 24831678 4 1 from carbazole 796:804 arg1 presence 862:869 the presence 858:869 the presence of Cu (0.2equiv) and Cs2CO3 (2equiv) 858:906 The crude iodides were involved in the N-arylation of pyrrole, indole, carbazole, pyrazole, indazole, imidazole and benzimidazole in the presence of Cu (0.2equiv) and Cs2CO3 (2equiv), and using acetonitrile as solvent (no other ligand) to provide after 24h reflux the expected N-arylated azoles in yields ranging from 33% to 81%. 24831678 2 2 theme % 531:531 arg1 yields 551:556 81%, 82%, 67% and 42% yields 529:556 81%, 82%, 67% and 42% yields 529:556 Subsequent interception of the 2-metalated derivatives using iodine as electrophile led to the iodides in 81%, 82%, 67% and 42% yields, respectively. 24831678 4 3 theme indole 788:793 arg1 N-arylation 764:774 the N-arylation 760:774 the N-arylation of pyrrole, indole, carbazole, pyrazole, indazole, imidazole and benzimidazole in the presence of Cu (0.2equiv) and Cs2CO3 (2equiv) 760:906 The crude iodides were involved in the N-arylation of pyrrole, indole, carbazole, pyrazole, indazole, imidazole and benzimidazole in the presence of Cu (0.2equiv) and Cs2CO3 (2equiv), and using acetonitrile as solvent (no other ligand) to provide after 24h reflux the expected N-arylated azoles in yields ranging from 33% to 81%. 24831678 4 4 from pyrazole 807:814 arg1 presence 862:869 the presence 858:869 the presence of Cu (0.2equiv) and Cs2CO3 (2equiv) 858:906 The crude iodides were involved in the N-arylation of pyrrole, indole, carbazole, pyrazole, indazole, imidazole and benzimidazole in the presence of Cu (0.2equiv) and Cs2CO3 (2equiv), and using acetonitrile as solvent (no other ligand) to provide after 24h reflux the expected N-arylated azoles in yields ranging from 33% to 81%. 24831678 6 5 theme N-arylation 1258:1268 arg1 yields 1270:1275 the N-arylation yields 1254:1275 the N-arylation yields 1254:1275 A further study with this azole evidenced the impact of 2,2,6,6-tetramethylpiperidine on the N-arylation yields. 24831678 5 6 theme lower 1116:1120 arg1 yields 1143:1148 lower 34%, 39%, 36% and 6% yields 1116:1148 lower 34%, 39%, 36% and 6% yields 1116:1148 Using benzotriazole also led to N-arylation products, but in lower 34%, 39%, 36% and 6% yields, respectively. 24831678 7 7 theme melanoma 1425:1432 arg1 cells 1434:1438 A2058 melanoma cells 1419:1438 A2058 melanoma cells 1419:1438 Most of the C,N'-linked bis-heterocycles thus synthesized (in particular those containing benzimidazole) induced a high growth inhibition of A2058 melanoma cells after a 72h treatment at 10(-5)M. 24831678 4 8 from indole 788:793 arg1 presence 862:869 the presence 858:869 the presence of Cu (0.2equiv) and Cs2CO3 (2equiv) 858:906 The crude iodides were involved in the N-arylation of pyrrole, indole, carbazole, pyrazole, indazole, imidazole and benzimidazole in the presence of Cu (0.2equiv) and Cs2CO3 (2equiv), and using acetonitrile as solvent (no other ligand) to provide after 24h reflux the expected N-arylated azoles in yields ranging from 33% to 81%. 24831678 4 9 from presence 862:869 arg1 N-arylation 764:774 the N-arylation 760:774 the N-arylation of pyrrole, indole, carbazole, pyrazole, indazole, imidazole and benzimidazole in the presence of Cu (0.2equiv) and Cs2CO3 (2equiv) 760:906 The crude iodides were involved in the N-arylation of pyrrole, indole, carbazole, pyrazole, indazole, imidazole and benzimidazole in the presence of Cu (0.2equiv) and Cs2CO3 (2equiv), and using acetonitrile as solvent (no other ligand) to provide after 24h reflux the expected N-arylated azoles in yields ranging from 33% to 81%. 24831678 2 10 theme % 541:541 arg1 yields 551:556 81%, 82%, 67% and 42% yields 529:556 81%, 82%, 67% and 42% yields 529:556 Subsequent interception of the 2-metalated derivatives using iodine as electrophile led to the iodides in 81%, 82%, 67% and 42% yields, respectively. 24831678 2 11 from iodides 518:524 arg1 yields 551:556 81%, 82%, 67% and 42% yields 529:556 81%, 82%, 67% and 42% yields 529:556 Subsequent interception of the 2-metalated derivatives using iodine as electrophile led to the iodides in 81%, 82%, 67% and 42% yields, respectively. 24831678 4 12 theme carbazole 796:804 arg1 N-arylation 764:774 the N-arylation 760:774 the N-arylation of pyrrole, indole, carbazole, pyrazole, indazole, imidazole and benzimidazole in the presence of Cu (0.2equiv) and Cs2CO3 (2equiv) 760:906 The crude iodides were involved in the N-arylation of pyrrole, indole, carbazole, pyrazole, indazole, imidazole and benzimidazole in the presence of Cu (0.2equiv) and Cs2CO3 (2equiv), and using acetonitrile as solvent (no other ligand) to provide after 24h reflux the expected N-arylated azoles in yields ranging from 33% to 81%. 24831678 5 13 dep lower 1116:1120 arg1 % 1124:1124 34% 1122:1124 34% 1122:1124 Using benzotriazole also led to N-arylation products, but in lower 34%, 39%, 36% and 6% yields, respectively. 24831678 5 13 dep lower 1116:1120 arg1 % 1129:1129 39% 1127:1129 39% 1127:1129 Using benzotriazole also led to N-arylation products, but in lower 34%, 39%, 36% and 6% yields, respectively. 24831678 5 13 dep lower 1116:1120 arg1 % 1134:1134 36% 1132:1134 36% 1132:1134 Using benzotriazole also led to N-arylation products, but in lower 34%, 39%, 36% and 6% yields, respectively. 24831678 5 13 dep lower 1116:1120 arg1 % 1141:1141 6% 1140:1141 6% 1140:1141 Using benzotriazole also led to N-arylation products, but in lower 34%, 39%, 36% and 6% yields, respectively. 24831678 4 14 theme Cs2CO3 892:897 arg1 presence 862:869 the presence 858:869 the presence of Cu (0.2equiv) and Cs2CO3 (2equiv) 858:906 The crude iodides were involved in the N-arylation of pyrrole, indole, carbazole, pyrazole, indazole, imidazole and benzimidazole in the presence of Cu (0.2equiv) and Cs2CO3 (2equiv), and using acetonitrile as solvent (no other ligand) to provide after 24h reflux the expected N-arylated azoles in yields ranging from 33% to 81%. 24831678 7 15 theme N'-linked 1292:1300 arg1 bis-heterocycles 1302:1317 N'-linked bis-heterocycles 1292:1317 N'-linked bis-heterocycles thus synthesized (in particular those containing benzimidazole) 1292:1381 Most of the C,N'-linked bis-heterocycles thus synthesized (in particular those containing benzimidazole) induced a high growth inhibition of A2058 melanoma cells after a 72h treatment at 10(-5)M. 24831678 7 15 theme N'-linked 1292:1300 arg1 C 1290:1290 the C 1286:1290 the C 1286:1290 Most of the C,N'-linked bis-heterocycles thus synthesized (in particular those containing benzimidazole) induced a high growth inhibition of A2058 melanoma cells after a 72h treatment at 10(-5)M. 24831678 7 15 theme N'-linked 1292:1300 arg1 particular 1340:1349 particular 1340:1349 particular 1340:1349 Most of the C,N'-linked bis-heterocycles thus synthesized (in particular those containing benzimidazole) induced a high growth inhibition of A2058 melanoma cells after a 72h treatment at 10(-5)M. 24831678 0 16 theme activity 142:149 arg1 evaluation 104:113 evaluation 104:113 evaluation 104:113 Synthesis of C,N'-linked bis-heterocycles using a deprotometalation-iodination-N-arylation sequence and evaluation of their antiproliferative activity in melanoma cells. 24831678 0 16 theme activity 142:149 arg1 sequence 91:98 a deprotometalation-iodination-N-arylation sequence 48:98 a deprotometalation-iodination-N-arylation sequence 48:98 Synthesis of C,N'-linked bis-heterocycles using a deprotometalation-iodination-N-arylation sequence and evaluation of their antiproliferative activity in melanoma cells. 24831678 4 17 theme expected 993:1000 arg1 azoles 1013:1018 the expected N-arylated azoles 989:1018 the expected N-arylated azoles in yields ranging from 33% to 81% 989:1052 The crude iodides were involved in the N-arylation of pyrrole, indole, carbazole, pyrazole, indazole, imidazole and benzimidazole in the presence of Cu (0.2equiv) and Cs2CO3 (2equiv), and using acetonitrile as solvent (no other ligand) to provide after 24h reflux the expected N-arylated azoles in yields ranging from 33% to 81%. 24831678 4 18 from azoles 1013:1018 arg1 yields 1023:1028 yields 1023:1028 yields ranging from 33% to 81% 1023:1052 The crude iodides were involved in the N-arylation of pyrrole, indole, carbazole, pyrazole, indazole, imidazole and benzimidazole in the presence of Cu (0.2equiv) and Cs2CO3 (2equiv), and using acetonitrile as solvent (no other ligand) to provide after 24h reflux the expected N-arylated azoles in yields ranging from 33% to 81%. 24831678 0 19 theme antiproliferative 124:140 arg1 activity 142:149 their antiproliferative activity 118:149 their antiproliferative activity in melanoma cells 118:167 Synthesis of C,N'-linked bis-heterocycles using a deprotometalation-iodination-N-arylation sequence and evaluation of their antiproliferative activity in melanoma cells. 24831678 7 20 theme growth 1398:1403 arg1 inhibition 1405:1414 a high growth inhibition 1391:1414 a high growth inhibition of A2058 melanoma cells 1391:1438 Most of the C,N'-linked bis-heterocycles thus synthesized (in particular those containing benzimidazole) induced a high growth inhibition of A2058 melanoma cells after a 72h treatment at 10(-5)M. 24831678 4 21 from pyrrole 779:785 arg1 presence 862:869 the presence 858:869 the presence of Cu (0.2equiv) and Cs2CO3 (2equiv) 858:906 The crude iodides were involved in the N-arylation of pyrrole, indole, carbazole, pyrazole, indazole, imidazole and benzimidazole in the presence of Cu (0.2equiv) and Cs2CO3 (2equiv), and using acetonitrile as solvent (no other ligand) to provide after 24h reflux the expected N-arylated azoles in yields ranging from 33% to 81%. 24831678 3 22 dep higher 590:595 arg1 more 602:605 more 602:605 more 602:605 These yields are higher (10% more) than those obtained using ZnCl2·TMEDA (0.5equiv) and LiTMP (1.5equiv), except in the case of benzoxazole (10% less). 24831678 4 23 from N-arylation 764:774 arg1 presence 862:869 the presence 858:869 the presence of Cu (0.2equiv) and Cs2CO3 (2equiv) 858:906 The crude iodides were involved in the N-arylation of pyrrole, indole, carbazole, pyrazole, indazole, imidazole and benzimidazole in the presence of Cu (0.2equiv) and Cs2CO3 (2equiv), and using acetonitrile as solvent (no other ligand) to provide after 24h reflux the expected N-arylated azoles in yields ranging from 33% to 81%. 24831678 7 24 dep particular 1340:1349 arg1 those 1351:1355 those 1351:1355 those 1351:1355 Most of the C,N'-linked bis-heterocycles thus synthesized (in particular those containing benzimidazole) induced a high growth inhibition of A2058 melanoma cells after a 72h treatment at 10(-5)M. 24831678 4 25 theme N-arylated 1002:1011 arg1 azoles 1013:1018 the expected N-arylated azoles 989:1018 the expected N-arylated azoles in yields ranging from 33% to 81% 989:1052 The crude iodides were involved in the N-arylation of pyrrole, indole, carbazole, pyrazole, indazole, imidazole and benzimidazole in the presence of Cu (0.2equiv) and Cs2CO3 (2equiv), and using acetonitrile as solvent (no other ligand) to provide after 24h reflux the expected N-arylated azoles in yields ranging from 33% to 81%. 24831678 6 26 theme 2,2,6,6-tetramethylpiperidine 1221:1249 arg1 impact 1211:1216 the impact 1207:1216 the impact of 2,2,6,6-tetramethylpiperidine on the N-arylation yields 1207:1275 A further study with this azole evidenced the impact of 2,2,6,6-tetramethylpiperidine on the N-arylation yields. 24831678 3 27 theme benzoxazole 701:711 arg1 case 693:696 the case 689:696 the case of benzoxazole (10% less) 689:722 These yields are higher (10% more) than those obtained using ZnCl2·TMEDA (0.5equiv) and LiTMP (1.5equiv), except in the case of benzoxazole (10% less). 24831678 4 28 theme pyrrole 779:785 arg1 N-arylation 764:774 the N-arylation 760:774 the N-arylation of pyrrole, indole, carbazole, pyrazole, indazole, imidazole and benzimidazole in the presence of Cu (0.2equiv) and Cs2CO3 (2equiv) 760:906 The crude iodides were involved in the N-arylation of pyrrole, indole, carbazole, pyrazole, indazole, imidazole and benzimidazole in the presence of Cu (0.2equiv) and Cs2CO3 (2equiv), and using acetonitrile as solvent (no other ligand) to provide after 24h reflux the expected N-arylated azoles in yields ranging from 33% to 81%. 24831678 2 29 theme Subsequent 423:432 arg1 interception 434:445 Subsequent interception 423:445 Subsequent interception of the 2-metalated derivatives using iodine as electrophile 423:505 Subsequent interception of the 2-metalated derivatives using iodine as electrophile led to the iodides in 81%, 82%, 67% and 42% yields, respectively. 24831678 7 30 theme 72h 1448:1450 arg1 treatment 1452:1460 a 72h treatment 1446:1460 a 72h treatment at 10(-5)M 1446:1471 Most of the C,N'-linked bis-heterocycles thus synthesized (in particular those containing benzimidazole) induced a high growth inhibition of A2058 melanoma cells after a 72h treatment at 10(-5)M. 24831678 0 31 theme melanoma 154:161 arg1 cells 163:167 melanoma cells 154:167 melanoma cells 154:167 Synthesis of C,N'-linked bis-heterocycles using a deprotometalation-iodination-N-arylation sequence and evaluation of their antiproliferative activity in melanoma cells. 24831678 0 32 link N'-linked 15:23 arg1 bis-heterocycles 25:40 N'-linked bis-heterocycles 15:40 N'-linked bis-heterocycles using a deprotometalation-iodination-N-arylation sequence and evaluation of their antiproliferative activity in melanoma cells 15:167 Synthesis of C,N'-linked bis-heterocycles using a deprotometalation-iodination-N-arylation sequence and evaluation of their antiproliferative activity in melanoma cells. 24831678 0 32 link N'-linked 15:23 arg1 Synthesis 0:8 Synthesis 0:8 Synthesis of C 0:13 Synthesis of C,N'-linked bis-heterocycles using a deprotometalation-iodination-N-arylation sequence and evaluation of their antiproliferative activity in melanoma cells. 24831678 0 33 theme C 13:13 arg1 bis-heterocycles 25:40 N'-linked bis-heterocycles 15:40 N'-linked bis-heterocycles using a deprotometalation-iodination-N-arylation sequence and evaluation of their antiproliferative activity in melanoma cells 15:167 Synthesis of C,N'-linked bis-heterocycles using a deprotometalation-iodination-N-arylation sequence and evaluation of their antiproliferative activity in melanoma cells. 24831678 0 33 theme C 13:13 arg1 Synthesis 0:8 Synthesis 0:8 Synthesis of C 0:13 Synthesis of C,N'-linked bis-heterocycles using a deprotometalation-iodination-N-arylation sequence and evaluation of their antiproliferative activity in melanoma cells. 24831678 7 34 theme cells 1434:1438 arg1 inhibition 1405:1414 a high growth inhibition 1391:1414 a high growth inhibition of A2058 melanoma cells 1391:1438 Most of the C,N'-linked bis-heterocycles thus synthesized (in particular those containing benzimidazole) induced a high growth inhibition of A2058 melanoma cells after a 72h treatment at 10(-5)M. 24831678 4 35 theme imidazole 827:835 arg1 N-arylation 764:774 the N-arylation 760:774 the N-arylation of pyrrole, indole, carbazole, pyrazole, indazole, imidazole and benzimidazole in the presence of Cu (0.2equiv) and Cs2CO3 (2equiv) 760:906 The crude iodides were involved in the N-arylation of pyrrole, indole, carbazole, pyrazole, indazole, imidazole and benzimidazole in the presence of Cu (0.2equiv) and Cs2CO3 (2equiv), and using acetonitrile as solvent (no other ligand) to provide after 24h reflux the expected N-arylated azoles in yields ranging from 33% to 81%. 24831678 0 36 from evaluation 104:113 arg1 cells 163:167 melanoma cells 154:167 melanoma cells 154:167 Synthesis of C,N'-linked bis-heterocycles using a deprotometalation-iodination-N-arylation sequence and evaluation of their antiproliferative activity in melanoma cells. 24831678 4 37 dep % 1045:1045 arg1 to 1047:1048 to 1047:1048 to 1047:1048 The crude iodides were involved in the N-arylation of pyrrole, indole, carbazole, pyrazole, indazole, imidazole and benzimidazole in the presence of Cu (0.2equiv) and Cs2CO3 (2equiv), and using acetonitrile as solvent (no other ligand) to provide after 24h reflux the expected N-arylated azoles in yields ranging from 33% to 81%. 24831678 1 38 dep 2,2,6,6-tetramethylpiperidide 376:404 arg1 3equiv 414:419 3equiv 414:419 3equiv 414:419 Benzothiophene, benzofuran, benzothiazole and benzoxazole were deprotometalated using the lithium-zinc combination prepared from ZnCl2·TMEDA (TMEDA=N,N,N',N'-tetramethylethylenediamine, 1equiv) and lithium 2,2,6,6-tetramethylpiperidide (LiTMP, 3equiv). 24831678 1 38 dep 2,2,6,6-tetramethylpiperidide 376:404 arg1 LiTMP 407:411 LiTMP 407:411 LiTMP 407:411 Benzothiophene, benzofuran, benzothiazole and benzoxazole were deprotometalated using the lithium-zinc combination prepared from ZnCl2·TMEDA (TMEDA=N,N,N',N'-tetramethylethylenediamine, 1equiv) and lithium 2,2,6,6-tetramethylpiperidide (LiTMP, 3equiv). 24831678 2 39 theme % 549:549 arg1 yields 551:556 81%, 82%, 67% and 42% yields 529:556 81%, 82%, 67% and 42% yields 529:556 Subsequent interception of the 2-metalated derivatives using iodine as electrophile led to the iodides in 81%, 82%, 67% and 42% yields, respectively. 24831678 1 40 dep ZnCl2·TMEDA 299:309 arg1 TMEDA=N 312:318 TMEDA=N 312:318 TMEDA=N 312:318 Benzothiophene, benzofuran, benzothiazole and benzoxazole were deprotometalated using the lithium-zinc combination prepared from ZnCl2·TMEDA (TMEDA=N,N,N',N'-tetramethylethylenediamine, 1equiv) and lithium 2,2,6,6-tetramethylpiperidide (LiTMP, 3equiv). 24831678 1 40 dep ZnCl2·TMEDA 299:309 arg1 N 320:320 N 320:320 N 320:320 Benzothiophene, benzofuran, benzothiazole and benzoxazole were deprotometalated using the lithium-zinc combination prepared from ZnCl2·TMEDA (TMEDA=N,N,N',N'-tetramethylethylenediamine, 1equiv) and lithium 2,2,6,6-tetramethylpiperidide (LiTMP, 3equiv). 24831678 7 41 contain containing 1357:1366 arg1 those 1351:1355 those 1351:1355 those 1351:1355 Most of the C,N'-linked bis-heterocycles thus synthesized (in particular those containing benzimidazole) induced a high growth inhibition of A2058 melanoma cells after a 72h treatment at 10(-5)M. 24831678 7 41 contain containing 1357:1366 arg2 benzimidazole 1368:1380 benzimidazole 1368:1380 benzimidazole 1368:1380 Most of the C,N'-linked bis-heterocycles thus synthesized (in particular those containing benzimidazole) induced a high growth inhibition of A2058 melanoma cells after a 72h treatment at 10(-5)M. 24831678 4 42 theme 24h 978:980 arg1 reflux 982:987 24h reflux 978:987 24h reflux 978:987 The crude iodides were involved in the N-arylation of pyrrole, indole, carbazole, pyrazole, indazole, imidazole and benzimidazole in the presence of Cu (0.2equiv) and Cs2CO3 (2equiv), and using acetonitrile as solvent (no other ligand) to provide after 24h reflux the expected N-arylated azoles in yields ranging from 33% to 81%. 24831678 2 43 theme derivatives 466:476 arg1 interception 434:445 Subsequent interception 423:445 Subsequent interception of the 2-metalated derivatives using iodine as electrophile 423:505 Subsequent interception of the 2-metalated derivatives using iodine as electrophile led to the iodides in 81%, 82%, 67% and 42% yields, respectively. 24831678 0 44 theme N'-linked 15:23 arg1 bis-heterocycles 25:40 N'-linked bis-heterocycles 15:40 N'-linked bis-heterocycles using a deprotometalation-iodination-N-arylation sequence and evaluation of their antiproliferative activity in melanoma cells 15:167 Synthesis of C,N'-linked bis-heterocycles using a deprotometalation-iodination-N-arylation sequence and evaluation of their antiproliferative activity in melanoma cells. 24831678 0 44 theme N'-linked 15:23 arg1 Synthesis 0:8 Synthesis 0:8 Synthesis of C 0:13 Synthesis of C,N'-linked bis-heterocycles using a deprotometalation-iodination-N-arylation sequence and evaluation of their antiproliferative activity in melanoma cells. 24831678 6 45 from impact 1211:1216 arg1 yields 1270:1275 the N-arylation yields 1254:1275 the N-arylation yields 1254:1275 A further study with this azole evidenced the impact of 2,2,6,6-tetramethylpiperidine on the N-arylation yields. 24831678 4 46 theme benzimidazole 841:853 arg1 N-arylation 764:774 the N-arylation 760:774 the N-arylation of pyrrole, indole, carbazole, pyrazole, indazole, imidazole and benzimidazole in the presence of Cu (0.2equiv) and Cs2CO3 (2equiv) 760:906 The crude iodides were involved in the N-arylation of pyrrole, indole, carbazole, pyrazole, indazole, imidazole and benzimidazole in the presence of Cu (0.2equiv) and Cs2CO3 (2equiv), and using acetonitrile as solvent (no other ligand) to provide after 24h reflux the expected N-arylated azoles in yields ranging from 33% to 81%. 24831678 0 47 from sequence 91:98 arg1 cells 163:167 melanoma cells 154:167 melanoma cells 154:167 Synthesis of C,N'-linked bis-heterocycles using a deprotometalation-iodination-N-arylation sequence and evaluation of their antiproliferative activity in melanoma cells. 24831678 2 48 theme 2-metalated 454:464 arg1 derivatives 466:476 the 2-metalated derivatives 450:476 the 2-metalated derivatives using iodine as electrophile 450:505 Subsequent interception of the 2-metalated derivatives using iodine as electrophile led to the iodides in 81%, 82%, 67% and 42% yields, respectively. 24831678 7 49 theme A2058 1419:1423 arg1 cells 1434:1438 A2058 melanoma cells 1419:1438 A2058 melanoma cells 1419:1438 Most of the C,N'-linked bis-heterocycles thus synthesized (in particular those containing benzimidazole) induced a high growth inhibition of A2058 melanoma cells after a 72h treatment at 10(-5)M. 24831678 4 50 from imidazole 827:835 arg1 presence 862:869 the presence 858:869 the presence of Cu (0.2equiv) and Cs2CO3 (2equiv) 858:906 The crude iodides were involved in the N-arylation of pyrrole, indole, carbazole, pyrazole, indazole, imidazole and benzimidazole in the presence of Cu (0.2equiv) and Cs2CO3 (2equiv), and using acetonitrile as solvent (no other ligand) to provide after 24h reflux the expected N-arylated azoles in yields ranging from 33% to 81%. 24831678 4 51 theme 33 1043:1044 arg1 % 1045:1045 % 1045:1045 % 1045:1045 The crude iodides were involved in the N-arylation of pyrrole, indole, carbazole, pyrazole, indazole, imidazole and benzimidazole in the presence of Cu (0.2equiv) and Cs2CO3 (2equiv), and using acetonitrile as solvent (no other ligand) to provide after 24h reflux the expected N-arylated azoles in yields ranging from 33% to 81%. 24831678 4 52 theme pyrazole 807:814 arg1 N-arylation 764:774 the N-arylation 760:774 the N-arylation of pyrrole, indole, carbazole, pyrazole, indazole, imidazole and benzimidazole in the presence of Cu (0.2equiv) and Cs2CO3 (2equiv) 760:906 The crude iodides were involved in the N-arylation of pyrrole, indole, carbazole, pyrazole, indazole, imidazole and benzimidazole in the presence of Cu (0.2equiv) and Cs2CO3 (2equiv), and using acetonitrile as solvent (no other ligand) to provide after 24h reflux the expected N-arylated azoles in yields ranging from 33% to 81%. 24831678 0 53 from activity 142:149 arg1 cells 163:167 melanoma cells 154:167 melanoma cells 154:167 Synthesis of C,N'-linked bis-heterocycles using a deprotometalation-iodination-N-arylation sequence and evaluation of their antiproliferative activity in melanoma cells. 24831678 4 54 theme 81 1050:1051 arg1 % 1045:1045 % 1045:1045 % 1045:1045 The crude iodides were involved in the N-arylation of pyrrole, indole, carbazole, pyrazole, indazole, imidazole and benzimidazole in the presence of Cu (0.2equiv) and Cs2CO3 (2equiv), and using acetonitrile as solvent (no other ligand) to provide after 24h reflux the expected N-arylated azoles in yields ranging from 33% to 81%. 24831678 4 55 theme Cu 874:875 arg1 presence 862:869 the presence 858:869 the presence of Cu (0.2equiv) and Cs2CO3 (2equiv) 858:906 The crude iodides were involved in the N-arylation of pyrrole, indole, carbazole, pyrazole, indazole, imidazole and benzimidazole in the presence of Cu (0.2equiv) and Cs2CO3 (2equiv), and using acetonitrile as solvent (no other ligand) to provide after 24h reflux the expected N-arylated azoles in yields ranging from 33% to 81%. 24831678 4 56 from indazole 817:824 arg1 presence 862:869 the presence 858:869 the presence of Cu (0.2equiv) and Cs2CO3 (2equiv) 858:906 The crude iodides were involved in the N-arylation of pyrrole, indole, carbazole, pyrazole, indazole, imidazole and benzimidazole in the presence of Cu (0.2equiv) and Cs2CO3 (2equiv), and using acetonitrile as solvent (no other ligand) to provide after 24h reflux the expected N-arylated azoles in yields ranging from 33% to 81%. 24831678 6 57 with study 1175:1179 arg1 azole 1191:1195 this azole 1186:1195 this azole 1186:1195 A further study with this azole evidenced the impact of 2,2,6,6-tetramethylpiperidine on the N-arylation yields. 24831678 4 58 theme other 947:951 arg1 ligand 953:958 no other ligand 944:958 no other ligand 944:958 The crude iodides were involved in the N-arylation of pyrrole, indole, carbazole, pyrazole, indazole, imidazole and benzimidazole in the presence of Cu (0.2equiv) and Cs2CO3 (2equiv), and using acetonitrile as solvent (no other ligand) to provide after 24h reflux the expected N-arylated azoles in yields ranging from 33% to 81%. 24831678 4 58 theme other 947:951 arg1 solvent 935:941 solvent 935:941 solvent (no other ligand) to provide after 24h reflux the expected N-arylated azoles in yields ranging from 33% to 81% 935:1052 The crude iodides were involved in the N-arylation of pyrrole, indole, carbazole, pyrazole, indazole, imidazole and benzimidazole in the presence of Cu (0.2equiv) and Cs2CO3 (2equiv), and using acetonitrile as solvent (no other ligand) to provide after 24h reflux the expected N-arylated azoles in yields ranging from 33% to 81%. 24831678 7 59 theme high 1393:1396 arg1 inhibition 1405:1414 a high growth inhibition 1391:1414 a high growth inhibition of A2058 melanoma cells 1391:1438 Most of the C,N'-linked bis-heterocycles thus synthesized (in particular those containing benzimidazole) induced a high growth inhibition of A2058 melanoma cells after a 72h treatment at 10(-5)M. 24831678 4 60 theme indazole 817:824 arg1 N-arylation 764:774 the N-arylation 760:774 the N-arylation of pyrrole, indole, carbazole, pyrazole, indazole, imidazole and benzimidazole in the presence of Cu (0.2equiv) and Cs2CO3 (2equiv) 760:906 The crude iodides were involved in the N-arylation of pyrrole, indole, carbazole, pyrazole, indazole, imidazole and benzimidazole in the presence of Cu (0.2equiv) and Cs2CO3 (2equiv), and using acetonitrile as solvent (no other ligand) to provide after 24h reflux the expected N-arylated azoles in yields ranging from 33% to 81%. 24831678 4 61 from benzimidazole 841:853 arg1 presence 862:869 the presence 858:869 the presence of Cu (0.2equiv) and Cs2CO3 (2equiv) 858:906 The crude iodides were involved in the N-arylation of pyrrole, indole, carbazole, pyrazole, indazole, imidazole and benzimidazole in the presence of Cu (0.2equiv) and Cs2CO3 (2equiv), and using acetonitrile as solvent (no other ligand) to provide after 24h reflux the expected N-arylated azoles in yields ranging from 33% to 81%. 24831678 0 62 from cells 163:167 arg1 evaluation 104:113 evaluation 104:113 evaluation 104:113 Synthesis of C,N'-linked bis-heterocycles using a deprotometalation-iodination-N-arylation sequence and evaluation of their antiproliferative activity in melanoma cells. 24831678 0 62 from cells 163:167 arg1 sequence 91:98 a deprotometalation-iodination-N-arylation sequence 48:98 a deprotometalation-iodination-N-arylation sequence 48:98 Synthesis of C,N'-linked bis-heterocycles using a deprotometalation-iodination-N-arylation sequence and evaluation of their antiproliferative activity in melanoma cells. 24831678 2 63 theme % 536:536 arg1 yields 551:556 81%, 82%, 67% and 42% yields 529:556 81%, 82%, 67% and 42% yields 529:556 Subsequent interception of the 2-metalated derivatives using iodine as electrophile led to the iodides in 81%, 82%, 67% and 42% yields, respectively. 24831678 1 64 theme lithium-zinc 260:271 arg1 combination 273:283 the lithium-zinc combination 256:283 the lithium-zinc combination prepared from ZnCl2·TMEDA (TMEDA=N,N,N',N'-tetramethylethylenediamine, 1equiv) 256:362 Benzothiophene, benzofuran, benzothiazole and benzoxazole were deprotometalated using the lithium-zinc combination prepared from ZnCl2·TMEDA (TMEDA=N,N,N',N'-tetramethylethylenediamine, 1equiv) and lithium 2,2,6,6-tetramethylpiperidide (LiTMP, 3equiv). 24831678 7 65 from M 1471:1471 arg1 treatment 1452:1460 a 72h treatment 1446:1460 a 72h treatment at 10(-5)M 1446:1471 Most of the C,N'-linked bis-heterocycles thus synthesized (in particular those containing benzimidazole) induced a high growth inhibition of A2058 melanoma cells after a 72h treatment at 10(-5)M. 24831678 7 66 link N'-linked 1292:1300 arg1 bis-heterocycles 1302:1317 N'-linked bis-heterocycles 1292:1317 N'-linked bis-heterocycles thus synthesized (in particular those containing benzimidazole) 1292:1381 Most of the C,N'-linked bis-heterocycles thus synthesized (in particular those containing benzimidazole) induced a high growth inhibition of A2058 melanoma cells after a 72h treatment at 10(-5)M. 24831678 7 66 link N'-linked 1292:1300 arg1 C 1290:1290 the C 1286:1290 the C 1286:1290 Most of the C,N'-linked bis-heterocycles thus synthesized (in particular those containing benzimidazole) induced a high growth inhibition of A2058 melanoma cells after a 72h treatment at 10(-5)M. 24831678 7 66 link N'-linked 1292:1300 arg1 particular 1340:1349 particular 1340:1349 particular 1340:1349 Most of the C,N'-linked bis-heterocycles thus synthesized (in particular those containing benzimidazole) induced a high growth inhibition of A2058 melanoma cells after a 72h treatment at 10(-5)M. 24831678 0 67 theme deprotometalation-iodination-N-arylation 50:89 arg1 sequence 91:98 a deprotometalation-iodination-N-arylation sequence 48:98 a deprotometalation-iodination-N-arylation sequence 48:98 Synthesis of C,N'-linked bis-heterocycles using a deprotometalation-iodination-N-arylation sequence and evaluation of their antiproliferative activity in melanoma cells. 24831678 1 68 theme lithium 368:374 arg1 2,2,6,6-tetramethylpiperidide 376:404 lithium 2,2,6,6-tetramethylpiperidide 368:404 lithium 2,2,6,6-tetramethylpiperidide (LiTMP, 3equiv) 368:420 Benzothiophene, benzofuran, benzothiazole and benzoxazole were deprotometalated using the lithium-zinc combination prepared from ZnCl2·TMEDA (TMEDA=N,N,N',N'-tetramethylethylenediamine, 1equiv) and lithium 2,2,6,6-tetramethylpiperidide (LiTMP, 3equiv). 24831678 4 69 theme crude 729:733 arg1 iodides 735:741 The crude iodides 725:741 The crude iodides 725:741 The crude iodides were involved in the N-arylation of pyrrole, indole, carbazole, pyrazole, indazole, imidazole and benzimidazole in the presence of Cu (0.2equiv) and Cs2CO3 (2equiv), and using acetonitrile as solvent (no other ligand) to provide after 24h reflux the expected N-arylated azoles in yields ranging from 33% to 81%. 24831678 7 70 dep synthesized 1324:1334 arg1 bis-heterocycles 1302:1317 N'-linked bis-heterocycles 1292:1317 N'-linked bis-heterocycles thus synthesized (in particular those containing benzimidazole) 1292:1381 Most of the C,N'-linked bis-heterocycles thus synthesized (in particular those containing benzimidazole) induced a high growth inhibition of A2058 melanoma cells after a 72h treatment at 10(-5)M. 24831678 7 70 dep synthesized 1324:1334 arg1 particular 1340:1349 particular 1340:1349 particular 1340:1349 Most of the C,N'-linked bis-heterocycles thus synthesized (in particular those containing benzimidazole) induced a high growth inhibition of A2058 melanoma cells after a 72h treatment at 10(-5)M. 24831678 5 71 theme N-arylation 1087:1097 arg1 products 1099:1106 N-arylation products 1087:1106 N-arylation products 1087:1106 Using benzotriazole also led to N-arylation products, but in lower 34%, 39%, 36% and 6% yields, respectively. 25389134 0 0 theme R345W 80:84 arg1 protein 108:114 a secreted protein 97:114 a secreted protein associated with retinal degeneration 97:151 Genetic ablation of N-linked glycosylation reveals two key folding pathways for R345W fibulin-3, a secreted protein associated with retinal degeneration. 25389134 0 0 theme R345W 80:84 arg1 fibulin-3 86:94 R345W fibulin-3 80:94 R345W fibulin-3 80:94 Genetic ablation of N-linked glycosylation reveals two key folding pathways for R345W fibulin-3, a secreted protein associated with retinal degeneration. 25389134 4 1 dep homeostasis 566:576 arg1 the 554:556 the 554:556 the 554:556 Therefore, we explored how N-glycosylation alters the protein homeostasis or proteostasis of wild-type (WT) and R345W F3 in ARPE-19 cells. 25389134 5 2 theme binding 664:670 arg1 assays 672:677 Enzymatic and lectin binding assays 643:677 assays 672:677 Enzymatic and lectin binding assays confirmed that WT and R345W F3 are both primarily N-glycosylated at Asn249. 25389134 2 3 theme malattia 349:356 arg1 leventinese 358:368 the retinal dystrophy malattia leventinese 327:368 the retinal dystrophy malattia leventinese 327:368 Inheritance of this mutation causes the retinal dystrophy malattia leventinese. 25389134 7 4 theme N249Q 886:890 arg1 mutation 892:899 an N249Q mutation 883:899 an N249Q mutation 883:899 Genetic elimination of F3 N-glycosylation (via an N249Q mutation) caused R345W F3 to aggregate intracellularly and adopt an altered secreted conformation. 25389134 1 5 theme inefficient 222:232 arg1 folding/secretion 237:253 inefficient F3 folding/secretion 222:253 inefficient F3 folding/secretion 222:253 An R345W mutation in the N-glycoprotein, fibulin-3 (F3), results in inefficient F3 folding/secretion and higher intracellular F3 levels. 25389134 5 6 dep both 714:717 arg1 primarily 719:727 primarily 719:727 primarily 719:727 Enzymatic and lectin binding assays confirmed that WT and R345W F3 are both primarily N-glycosylated at Asn249. 25389134 5 6 dep both 714:717 arg1 N-glycosylated 729:742 N-glycosylated 729:742 N-glycosylated 729:742 Enzymatic and lectin binding assays confirmed that WT and R345W F3 are both primarily N-glycosylated at Asn249. 25389134 10 7 theme F3 1466:1467 arg1 secretion 1469:1477 only N249Q/R345W F3 secretion 1449:1477 only N249Q/R345W F3 secretion (by 62%) 1449:1486 Inhibition of GRP94 ATPase activity reduced only N249Q/R345W F3 secretion (by 62%), demonstrating this variant's unique reliance on GRP94 for secretion. 25389134 0 8 link N-linked 20:27 arg1 glycosylation 29:41 N-linked glycosylation 20:41 N-linked glycosylation 20:41 Genetic ablation of N-linked glycosylation reveals two key folding pathways for R345W fibulin-3, a secreted protein associated with retinal degeneration. 25389134 2 9 theme dystrophy 339:347 arg1 leventinese 358:368 the retinal dystrophy malattia leventinese 327:368 the retinal dystrophy malattia leventinese 327:368 Inheritance of this mutation causes the retinal dystrophy malattia leventinese. 25389134 1 10 theme F3 234:235 arg1 folding/secretion 237:253 inefficient F3 folding/secretion 222:253 inefficient F3 folding/secretion 222:253 An R345W mutation in the N-glycoprotein, fibulin-3 (F3), results in inefficient F3 folding/secretion and higher intracellular F3 levels. 25389134 10 11 theme activity 1432:1439 arg1 Inhibition 1405:1414 Inhibition 1405:1414 Inhibition of GRP94 ATPase activity 1405:1439 Inhibition of GRP94 ATPase activity reduced only N249Q/R345W F3 secretion (by 62%), demonstrating this variant's unique reliance on GRP94 for secretion. 25389134 1 12 gly N-glycoprotein 179:192 arg1 N-glycoprotein 179:192 the N-glycoprotein 175:192 the N-glycoprotein 175:192 An R345W mutation in the N-glycoprotein, fibulin-3 (F3), results in inefficient F3 folding/secretion and higher intracellular F3 levels. 25389134 7 13 theme altered 960:966 arg1 conformation 977:988 an altered secreted conformation 957:988 an altered secreted conformation 957:988 Genetic elimination of F3 N-glycosylation (via an N249Q mutation) caused R345W F3 to aggregate intracellularly and adopt an altered secreted conformation. 25389134 3 14 theme common 399:404 arg1 glycosylation 380:392 N-Linked glycosylation 371:392 N-Linked glycosylation 371:392 N-Linked glycosylation is a common cotranslational protein modification that can regulate protein folding efficiency and energetics. 25389134 3 14 theme common 399:404 arg1 modification 430:441 a common cotranslational protein modification 397:441 a common cotranslational protein modification that can regulate protein folding efficiency and energetics 397:501 N-Linked glycosylation is a common cotranslational protein modification that can regulate protein folding efficiency and energetics. 25389134 11 15 theme WT 1608:1609 arg1 F3 1611:1612 WT F3 1608:1612 WT F3 1608:1612 These observations suggest that R345W F3, but not WT F3, requires N-glycosylation to acquire a stable, native-like structure. 25389134 11 16 theme stable 1653:1658 arg1 structure 1673:1681 a stable, native-like structure 1651:1681 structure 1673:1681 These observations suggest that R345W F3, but not WT F3, requires N-glycosylation to acquire a stable, native-like structure. 25389134 10 17 theme only 1449:1452 arg1 secretion 1469:1477 only N249Q/R345W F3 secretion 1449:1477 only N249Q/R345W F3 secretion (by 62%) 1449:1486 Inhibition of GRP94 ATPase activity reduced only N249Q/R345W F3 secretion (by 62%), demonstrating this variant's unique reliance on GRP94 for secretion. 25389134 7 18 theme F3 859:860 arg1 N-glycosylation 862:876 F3 N-glycosylation 859:876 F3 N-glycosylation (via an N249Q mutation) 859:900 Genetic elimination of F3 N-glycosylation (via an N249Q mutation) caused R345W F3 to aggregate intracellularly and adopt an altered secreted conformation. 25389134 0 19 theme secreted 99:106 arg1 protein 108:114 a secreted protein 97:114 a secreted protein associated with retinal degeneration 97:151 Genetic ablation of N-linked glycosylation reveals two key folding pathways for R345W fibulin-3, a secreted protein associated with retinal degeneration. 25389134 0 19 theme secreted 99:106 arg1 fibulin-3 86:94 R345W fibulin-3 80:94 R345W fibulin-3 80:94 Genetic ablation of N-linked glycosylation reveals two key folding pathways for R345W fibulin-3, a secreted protein associated with retinal degeneration. 25389134 4 20 dep wild-type 597:605 arg1 WT 608:609 WT 608:609 WT 608:609 Therefore, we explored how N-glycosylation alters the protein homeostasis or proteostasis of wild-type (WT) and R345W F3 in ARPE-19 cells. 25389134 8 21 dep lectins 1123:1129 arg1 lectins 1123:1129 the ER lectins calnexin and calreticulin 1116:1155 the ER lectins calnexin and calreticulin 1116:1155 The endoplasmic reticulum (ER) chaperones GRP78 (glucose-regulated protein 78) and GRP94 (glucose-regulated protein 94), and the ER lectins calnexin and calreticulin were identified as F3 binding partners by immunoprecipitation. 25389134 8 21 dep lectins 1123:1129 arg1 calreticulin 1144:1155 calreticulin 1144:1155 calreticulin 1144:1155 The endoplasmic reticulum (ER) chaperones GRP78 (glucose-regulated protein 78) and GRP94 (glucose-regulated protein 94), and the ER lectins calnexin and calreticulin were identified as F3 binding partners by immunoprecipitation. 25389134 8 21 dep lectins 1123:1129 arg1 calnexin 1131:1138 calnexin 1131:1138 calnexin 1131:1138 The endoplasmic reticulum (ER) chaperones GRP78 (glucose-regulated protein 78) and GRP94 (glucose-regulated protein 94), and the ER lectins calnexin and calreticulin were identified as F3 binding partners by immunoprecipitation. 25389134 7 22 theme N-glycosylation 862:876 arg1 elimination 844:854 Genetic elimination 836:854 Genetic elimination of F3 N-glycosylation (via an N249Q mutation) 836:900 Genetic elimination of F3 N-glycosylation (via an N249Q mutation) caused R345W F3 to aggregate intracellularly and adopt an altered secreted conformation. 25389134 5 23 theme Enzymatic 643:651 arg1 assays 672:677 Enzymatic and lectin binding assays 643:677 assays 672:677 Enzymatic and lectin binding assays confirmed that WT and R345W F3 are both primarily N-glycosylated at Asn249. 25389134 8 24 theme reticulum 1007:1015 arg1 GRP78 1033:1037 GRP78 1033:1037 GRP78 1033:1037 The endoplasmic reticulum (ER) chaperones GRP78 (glucose-regulated protein 78) and GRP94 (glucose-regulated protein 94), and the ER lectins calnexin and calreticulin were identified as F3 binding partners by immunoprecipitation. 25389134 8 24 theme reticulum 1007:1015 arg1 lectins 1123:1129 the ER lectins calnexin and calreticulin 1116:1155 the ER lectins calnexin and calreticulin 1116:1155 The endoplasmic reticulum (ER) chaperones GRP78 (glucose-regulated protein 78) and GRP94 (glucose-regulated protein 94), and the ER lectins calnexin and calreticulin were identified as F3 binding partners by immunoprecipitation. 25389134 8 24 theme reticulum 1007:1015 arg1 chaperones 1022:1031 The endoplasmic reticulum (ER) chaperones 991:1031 The endoplasmic reticulum (ER) chaperones GRP78 (glucose-regulated protein 78) and GRP94 (glucose-regulated protein 94) 991:1109 The endoplasmic reticulum (ER) chaperones GRP78 (glucose-regulated protein 78) and GRP94 (glucose-regulated protein 94), and the ER lectins calnexin and calreticulin were identified as F3 binding partners by immunoprecipitation. 25389134 8 24 theme reticulum 1007:1015 arg1 partners 1187:1194 F3 binding partners 1176:1194 F3 binding partners 1176:1194 The endoplasmic reticulum (ER) chaperones GRP78 (glucose-regulated protein 78) and GRP94 (glucose-regulated protein 94), and the ER lectins calnexin and calreticulin were identified as F3 binding partners by immunoprecipitation. 25389134 8 24 theme reticulum 1007:1015 arg1 GRP94 1074:1078 GRP94 1074:1078 GRP94 1074:1078 The endoplasmic reticulum (ER) chaperones GRP78 (glucose-regulated protein 78) and GRP94 (glucose-regulated protein 94), and the ER lectins calnexin and calreticulin were identified as F3 binding partners by immunoprecipitation. 25389134 4 25 from wild-type 597:605 arg1 cells 636:640 ARPE-19 cells 628:640 ARPE-19 cells 628:640 Therefore, we explored how N-glycosylation alters the protein homeostasis or proteostasis of wild-type (WT) and R345W F3 in ARPE-19 cells. 25389134 3 26 theme protein 461:467 arg1 folding 469:475 protein folding efficiency and energetics 461:501 folding 469:475 N-Linked glycosylation is a common cotranslational protein modification that can regulate protein folding efficiency and energetics. 25389134 8 27 theme ER 1120:1121 arg1 lectins 1123:1129 the ER lectins calnexin and calreticulin 1116:1155 the ER lectins calnexin and calreticulin 1116:1155 The endoplasmic reticulum (ER) chaperones GRP78 (glucose-regulated protein 78) and GRP94 (glucose-regulated protein 94), and the ER lectins calnexin and calreticulin were identified as F3 binding partners by immunoprecipitation. 25389134 8 27 theme ER 1120:1121 arg1 calreticulin 1144:1155 calreticulin 1144:1155 calreticulin 1144:1155 The endoplasmic reticulum (ER) chaperones GRP78 (glucose-regulated protein 78) and GRP94 (glucose-regulated protein 94), and the ER lectins calnexin and calreticulin were identified as F3 binding partners by immunoprecipitation. 25389134 8 27 theme ER 1120:1121 arg1 calnexin 1131:1138 calnexin 1131:1138 calnexin 1131:1138 The endoplasmic reticulum (ER) chaperones GRP78 (glucose-regulated protein 78) and GRP94 (glucose-regulated protein 94), and the ER lectins calnexin and calreticulin were identified as F3 binding partners by immunoprecipitation. 25389134 8 27 theme ER 1120:1121 arg1 partners 1187:1194 F3 binding partners 1176:1194 F3 binding partners 1176:1194 The endoplasmic reticulum (ER) chaperones GRP78 (glucose-regulated protein 78) and GRP94 (glucose-regulated protein 94), and the ER lectins calnexin and calreticulin were identified as F3 binding partners by immunoprecipitation. 25389134 8 27 theme ER 1120:1121 arg1 chaperones 1022:1031 The endoplasmic reticulum (ER) chaperones 991:1031 The endoplasmic reticulum (ER) chaperones GRP78 (glucose-regulated protein 78) and GRP94 (glucose-regulated protein 94) 991:1109 The endoplasmic reticulum (ER) chaperones GRP78 (glucose-regulated protein 78) and GRP94 (glucose-regulated protein 94), and the ER lectins calnexin and calreticulin were identified as F3 binding partners by immunoprecipitation. 25389134 8 28 theme endoplasmic 995:1005 arg1 reticulum 1007:1015 The endoplasmic reticulum 991:1015 The endoplasmic reticulum (ER) chaperones GRP78 (glucose-regulated protein 78) and GRP94 (glucose-regulated protein 94) 991:1109 The endoplasmic reticulum (ER) chaperones GRP78 (glucose-regulated protein 78) and GRP94 (glucose-regulated protein 94), and the ER lectins calnexin and calreticulin were identified as F3 binding partners by immunoprecipitation. 25389134 8 28 theme endoplasmic 995:1005 arg1 ER 1018:1019 ER 1018:1019 ER 1018:1019 The endoplasmic reticulum (ER) chaperones GRP78 (glucose-regulated protein 78) and GRP94 (glucose-regulated protein 94), and the ER lectins calnexin and calreticulin were identified as F3 binding partners by immunoprecipitation. 25389134 0 29 theme Genetic 0:6 arg1 ablation 8:15 Genetic ablation 0:15 Genetic ablation of N-linked glycosylation 0:41 Genetic ablation of N-linked glycosylation reveals two key folding pathways for R345W fibulin-3, a secreted protein associated with retinal degeneration. 25389134 1 30 theme higher 259:264 arg1 levels 283:288 higher intracellular F3 levels 259:288 higher intracellular F3 levels 259:288 An R345W mutation in the N-glycoprotein, fibulin-3 (F3), results in inefficient F3 folding/secretion and higher intracellular F3 levels. 25389134 5 31 theme lectin 657:662 arg1 assays 672:677 Enzymatic and lectin binding assays 643:677 assays 672:677 Enzymatic and lectin binding assays confirmed that WT and R345W F3 are both primarily N-glycosylated at Asn249. 25389134 10 32 theme ATPase 1425:1430 arg1 activity 1432:1439 GRP94 ATPase activity 1419:1439 GRP94 ATPase activity 1419:1439 Inhibition of GRP94 ATPase activity reduced only N249Q/R345W F3 secretion (by 62%), demonstrating this variant's unique reliance on GRP94 for secretion. 25389134 8 33 dep chaperones 1022:1031 arg1 GRP78 1033:1037 GRP78 1033:1037 GRP78 1033:1037 The endoplasmic reticulum (ER) chaperones GRP78 (glucose-regulated protein 78) and GRP94 (glucose-regulated protein 94), and the ER lectins calnexin and calreticulin were identified as F3 binding partners by immunoprecipitation. 25389134 8 33 dep chaperones 1022:1031 arg1 protein 1058:1064 glucose-regulated protein 78 1040:1067 glucose-regulated protein 78 1040:1067 The endoplasmic reticulum (ER) chaperones GRP78 (glucose-regulated protein 78) and GRP94 (glucose-regulated protein 94), and the ER lectins calnexin and calreticulin were identified as F3 binding partners by immunoprecipitation. 25389134 8 33 dep chaperones 1022:1031 arg1 GRP94 1074:1078 GRP94 1074:1078 GRP94 1074:1078 The endoplasmic reticulum (ER) chaperones GRP78 (glucose-regulated protein 78) and GRP94 (glucose-regulated protein 94), and the ER lectins calnexin and calreticulin were identified as F3 binding partners by immunoprecipitation. 25389134 8 33 dep chaperones 1022:1031 arg1 protein 1099:1105 glucose-regulated protein 94 1081:1108 glucose-regulated protein 94 1081:1108 The endoplasmic reticulum (ER) chaperones GRP78 (glucose-regulated protein 78) and GRP94 (glucose-regulated protein 94), and the ER lectins calnexin and calreticulin were identified as F3 binding partners by immunoprecipitation. 25389134 8 33 dep chaperones 1022:1031 arg1 chaperones 1022:1031 The endoplasmic reticulum (ER) chaperones 991:1031 The endoplasmic reticulum (ER) chaperones GRP78 (glucose-regulated protein 78) and GRP94 (glucose-regulated protein 94) 991:1109 The endoplasmic reticulum (ER) chaperones GRP78 (glucose-regulated protein 78) and GRP94 (glucose-regulated protein 94), and the ER lectins calnexin and calreticulin were identified as F3 binding partners by immunoprecipitation. 25389134 0 34 theme N-linked 20:27 arg1 glycosylation 29:41 N-linked glycosylation 20:41 N-linked glycosylation 20:41 Genetic ablation of N-linked glycosylation reveals two key folding pathways for R345W fibulin-3, a secreted protein associated with retinal degeneration. 25389134 1 35 theme intracellular 266:278 arg1 levels 283:288 higher intracellular F3 levels 259:288 higher intracellular F3 levels 259:288 An R345W mutation in the N-glycoprotein, fibulin-3 (F3), results in inefficient F3 folding/secretion and higher intracellular F3 levels. 25389134 6 36 theme F3 803:804 arg1 secretion 806:814 R345W F3 secretion 797:814 R345W F3 secretion 797:814 Tunicamycin treatment selectively reduced R345W F3 secretion by 87% (vs. WT F3). 25389134 8 37 theme binding 1179:1185 arg1 lectins 1123:1129 the ER lectins calnexin and calreticulin 1116:1155 the ER lectins calnexin and calreticulin 1116:1155 The endoplasmic reticulum (ER) chaperones GRP78 (glucose-regulated protein 78) and GRP94 (glucose-regulated protein 94), and the ER lectins calnexin and calreticulin were identified as F3 binding partners by immunoprecipitation. 25389134 8 37 theme binding 1179:1185 arg1 chaperones 1022:1031 The endoplasmic reticulum (ER) chaperones 991:1031 The endoplasmic reticulum (ER) chaperones GRP78 (glucose-regulated protein 78) and GRP94 (glucose-regulated protein 94) 991:1109 The endoplasmic reticulum (ER) chaperones GRP78 (glucose-regulated protein 78) and GRP94 (glucose-regulated protein 94), and the ER lectins calnexin and calreticulin were identified as F3 binding partners by immunoprecipitation. 25389134 8 37 theme binding 1179:1185 arg1 partners 1187:1194 F3 binding partners 1176:1194 F3 binding partners 1176:1194 The endoplasmic reticulum (ER) chaperones GRP78 (glucose-regulated protein 78) and GRP94 (glucose-regulated protein 94), and the ER lectins calnexin and calreticulin were identified as F3 binding partners by immunoprecipitation. 25389134 6 38 theme WT 828:829 arg1 F3 831:832 WT F3 828:832 WT F3 828:832 Tunicamycin treatment selectively reduced R345W F3 secretion by 87% (vs. WT F3). 25389134 10 39 theme GRP94 1419:1423 arg1 activity 1432:1439 GRP94 ATPase activity 1419:1439 GRP94 ATPase activity 1419:1439 Inhibition of GRP94 ATPase activity reduced only N249Q/R345W F3 secretion (by 62%), demonstrating this variant's unique reliance on GRP94 for secretion. 25389134 4 40 from proteostasis 581:592 arg1 cells 636:640 ARPE-19 cells 628:640 ARPE-19 cells 628:640 Therefore, we explored how N-glycosylation alters the protein homeostasis or proteostasis of wild-type (WT) and R345W F3 in ARPE-19 cells. 25389134 1 41 theme F3 280:281 arg1 levels 283:288 higher intracellular F3 levels 259:288 higher intracellular F3 levels 259:288 An R345W mutation in the N-glycoprotein, fibulin-3 (F3), results in inefficient F3 folding/secretion and higher intracellular F3 levels. 25389134 7 42 theme secreted 968:975 arg1 conformation 977:988 an altered secreted conformation 957:988 an altered secreted conformation 957:988 Genetic elimination of F3 N-glycosylation (via an N249Q mutation) caused R345W F3 to aggregate intracellularly and adopt an altered secreted conformation. 25389134 1 43 theme R345W 157:161 arg1 fibulin-3 195:203 fibulin-3 195:203 fibulin-3 (F3) 195:208 An R345W mutation in the N-glycoprotein, fibulin-3 (F3), results in inefficient F3 folding/secretion and higher intracellular F3 levels. 25389134 1 43 theme R345W 157:161 arg1 mutation 163:170 An R345W mutation 154:170 An R345W mutation in the N-glycoprotein 154:192 An R345W mutation in the N-glycoprotein, fibulin-3 (F3), results in inefficient F3 folding/secretion and higher intracellular F3 levels. 25389134 3 44 theme protein 422:428 arg1 glycosylation 380:392 N-Linked glycosylation 371:392 N-Linked glycosylation 371:392 N-Linked glycosylation is a common cotranslational protein modification that can regulate protein folding efficiency and energetics. 25389134 3 44 theme protein 422:428 arg1 modification 430:441 a common cotranslational protein modification 397:441 a common cotranslational protein modification that can regulate protein folding efficiency and energetics 397:501 N-Linked glycosylation is a common cotranslational protein modification that can regulate protein folding efficiency and energetics. 25389134 4 45 theme wild-type 597:605 arg1 homeostasis 566:576 protein homeostasis 558:576 protein homeostasis 558:576 Therefore, we explored how N-glycosylation alters the protein homeostasis or proteostasis of wild-type (WT) and R345W F3 in ARPE-19 cells. 25389134 4 45 theme wild-type 597:605 arg1 proteostasis 581:592 proteostasis 581:592 proteostasis 581:592 Therefore, we explored how N-glycosylation alters the protein homeostasis or proteostasis of wild-type (WT) and R345W F3 in ARPE-19 cells. 25389134 0 46 theme retinal 132:138 arg1 degeneration 140:151 retinal degeneration 132:151 retinal degeneration 132:151 Genetic ablation of N-linked glycosylation reveals two key folding pathways for R345W fibulin-3, a secreted protein associated with retinal degeneration. 25389134 0 47 theme glycosylation 29:41 arg1 ablation 8:15 Genetic ablation 0:15 Genetic ablation of N-linked glycosylation 0:41 Genetic ablation of N-linked glycosylation reveals two key folding pathways for R345W fibulin-3, a secreted protein associated with retinal degeneration. 25389134 4 48 theme protein 558:564 arg1 homeostasis 566:576 protein homeostasis 558:576 protein homeostasis 558:576 Therefore, we explored how N-glycosylation alters the protein homeostasis or proteostasis of wild-type (WT) and R345W F3 in ARPE-19 cells. 25389134 4 49 from homeostasis 566:576 arg1 cells 636:640 ARPE-19 cells 628:640 ARPE-19 cells 628:640 Therefore, we explored how N-glycosylation alters the protein homeostasis or proteostasis of wild-type (WT) and R345W F3 in ARPE-19 cells. 25389134 11 50 theme native-like 1661:1671 arg1 structure 1673:1681 a stable, native-like structure 1651:1681 structure 1673:1681 These observations suggest that R345W F3, but not WT F3, requires N-glycosylation to acquire a stable, native-like structure. 25389134 3 51 theme N-Linked 371:378 arg1 glycosylation 380:392 N-Linked glycosylation 371:392 N-Linked glycosylation 371:392 N-Linked glycosylation is a common cotranslational protein modification that can regulate protein folding efficiency and energetics. 25389134 3 51 theme N-Linked 371:378 arg1 modification 430:441 a common cotranslational protein modification 397:441 a common cotranslational protein modification that can regulate protein folding efficiency and energetics 397:501 N-Linked glycosylation is a common cotranslational protein modification that can regulate protein folding efficiency and energetics. 25389134 6 52 theme R345W 797:801 arg1 secretion 806:814 R345W F3 secretion 797:814 R345W F3 secretion 797:814 Tunicamycin treatment selectively reduced R345W F3 secretion by 87% (vs. WT F3). 25389134 0 53 theme key 55:57 arg1 pathways 67:74 two key folding pathways 51:74 two key folding pathways for R345W fibulin-3, a secreted protein associated with retinal degeneration 51:151 Genetic ablation of N-linked glycosylation reveals two key folding pathways for R345W fibulin-3, a secreted protein associated with retinal degeneration. 25389134 7 54 theme Genetic 836:842 arg1 elimination 844:854 Genetic elimination 836:854 Genetic elimination of F3 N-glycosylation (via an N249Q mutation) 836:900 Genetic elimination of F3 N-glycosylation (via an N249Q mutation) caused R345W F3 to aggregate intracellularly and adopt an altered secreted conformation. 25389134 5 55 from Asn249 747:752 arg1 N-glycosylated 729:742 N-glycosylated 729:742 N-glycosylated 729:742 Enzymatic and lectin binding assays confirmed that WT and R345W F3 are both primarily N-glycosylated at Asn249. 25389134 2 56 theme retinal 331:337 arg1 leventinese 358:368 the retinal dystrophy malattia leventinese 327:368 the retinal dystrophy malattia leventinese 327:368 Inheritance of this mutation causes the retinal dystrophy malattia leventinese. 25389134 3 57 theme cotranslational 406:420 arg1 glycosylation 380:392 N-Linked glycosylation 371:392 N-Linked glycosylation 371:392 N-Linked glycosylation is a common cotranslational protein modification that can regulate protein folding efficiency and energetics. 25389134 3 57 theme cotranslational 406:420 arg1 modification 430:441 a common cotranslational protein modification 397:441 a common cotranslational protein modification that can regulate protein folding efficiency and energetics 397:501 N-Linked glycosylation is a common cotranslational protein modification that can regulate protein folding efficiency and energetics. 25389134 10 58 theme unique 1518:1523 arg1 reliance 1525:1532 this variant's unique reliance 1503:1532 this variant's unique reliance on GRP94 for secretion 1503:1555 Inhibition of GRP94 ATPase activity reduced only N249Q/R345W F3 secretion (by 62%), demonstrating this variant's unique reliance on GRP94 for secretion. 25389134 8 59 theme glucose-regulated 1040:1056 arg1 GRP78 1033:1037 GRP78 1033:1037 GRP78 1033:1037 The endoplasmic reticulum (ER) chaperones GRP78 (glucose-regulated protein 78) and GRP94 (glucose-regulated protein 94), and the ER lectins calnexin and calreticulin were identified as F3 binding partners by immunoprecipitation. 25389134 8 59 theme glucose-regulated 1040:1056 arg1 protein 1058:1064 glucose-regulated protein 78 1040:1067 glucose-regulated protein 78 1040:1067 The endoplasmic reticulum (ER) chaperones GRP78 (glucose-regulated protein 78) and GRP94 (glucose-regulated protein 94), and the ER lectins calnexin and calreticulin were identified as F3 binding partners by immunoprecipitation. 25389134 10 60 theme N249Q/R345W 1454:1464 arg1 secretion 1469:1477 only N249Q/R345W F3 secretion 1449:1477 only N249Q/R345W F3 secretion (by 62%) 1449:1486 Inhibition of GRP94 ATPase activity reduced only N249Q/R345W F3 secretion (by 62%), demonstrating this variant's unique reliance on GRP94 for secretion. 25389134 9 61 theme N-glycosylated 1376:1389 arg1 counterparts 1391:1402 their N-glycosylated counterparts 1370:1402 their N-glycosylated counterparts 1370:1402 Significantly more N249Q and N249Q/R345W F3 interacted with GRP94, while substantially less N249Q and N249Q/R345W interacted with the ER lectins than their N-glycosylated counterparts. 25389134 8 62 theme glucose-regulated 1081:1097 arg1 GRP94 1074:1078 GRP94 1074:1078 GRP94 1074:1078 The endoplasmic reticulum (ER) chaperones GRP78 (glucose-regulated protein 78) and GRP94 (glucose-regulated protein 94), and the ER lectins calnexin and calreticulin were identified as F3 binding partners by immunoprecipitation. 25389134 8 62 theme glucose-regulated 1081:1097 arg1 protein 1099:1105 glucose-regulated protein 94 1081:1108 glucose-regulated protein 94 1081:1108 The endoplasmic reticulum (ER) chaperones GRP78 (glucose-regulated protein 78) and GRP94 (glucose-regulated protein 94), and the ER lectins calnexin and calreticulin were identified as F3 binding partners by immunoprecipitation. 25389134 3 63 dep folding 469:475 arg1 efficiency 477:486 efficiency 477:486 efficiency 477:486 N-Linked glycosylation is a common cotranslational protein modification that can regulate protein folding efficiency and energetics. 25389134 9 64 gly N-glycosylated 1376:1389 arg1 counterparts 1391:1402 their N-glycosylated counterparts 1370:1402 their N-glycosylated counterparts 1370:1402 Significantly more N249Q and N249Q/R345W F3 interacted with GRP94, while substantially less N249Q and N249Q/R345W interacted with the ER lectins than their N-glycosylated counterparts. 25389134 5 65 gly N-glycosylated 729:742 arg1 WT 694:695 WT 694:695 WT 694:695 Enzymatic and lectin binding assays confirmed that WT and R345W F3 are both primarily N-glycosylated at Asn249. 25389134 5 65 gly N-glycosylated 729:742 arg1 F3 707:708 F3 707:708 F3 707:708 Enzymatic and lectin binding assays confirmed that WT and R345W F3 are both primarily N-glycosylated at Asn249. 25389134 5 65 gly N-glycosylated 729:742 arg2 Asn249 747:752 Asn249 747:752 Asn249 747:752 Enzymatic and lectin binding assays confirmed that WT and R345W F3 are both primarily N-glycosylated at Asn249. 25389134 7 66 theme R345W 909:913 arg1 F3 915:916 R345W F3 909:916 R345W F3 to aggregate 909:929 Genetic elimination of F3 N-glycosylation (via an N249Q mutation) caused R345W F3 to aggregate intracellularly and adopt an altered secreted conformation. 25389134 6 67 theme Tunicamycin 755:765 arg1 treatment 767:775 Tunicamycin treatment 755:775 Tunicamycin treatment 755:775 Tunicamycin treatment selectively reduced R345W F3 secretion by 87% (vs. WT F3). 25389134 2 68 theme mutation 311:318 arg1 Inheritance 291:301 Inheritance 291:301 Inheritance of this mutation 291:318 Inheritance of this mutation causes the retinal dystrophy malattia leventinese. 25389134 4 69 theme F3 622:623 arg1 homeostasis 566:576 protein homeostasis 558:576 protein homeostasis 558:576 Therefore, we explored how N-glycosylation alters the protein homeostasis or proteostasis of wild-type (WT) and R345W F3 in ARPE-19 cells. 25389134 4 69 theme F3 622:623 arg1 proteostasis 581:592 proteostasis 581:592 proteostasis 581:592 Therefore, we explored how N-glycosylation alters the protein homeostasis or proteostasis of wild-type (WT) and R345W F3 in ARPE-19 cells. 25389134 4 70 from cells 636:640 arg1 homeostasis 566:576 protein homeostasis 558:576 protein homeostasis 558:576 Therefore, we explored how N-glycosylation alters the protein homeostasis or proteostasis of wild-type (WT) and R345W F3 in ARPE-19 cells. 25389134 4 70 from cells 636:640 arg1 wild-type 597:605 wild-type 597:605 wild-type 597:605 Therefore, we explored how N-glycosylation alters the protein homeostasis or proteostasis of wild-type (WT) and R345W F3 in ARPE-19 cells. 25389134 4 70 from cells 636:640 arg1 proteostasis 581:592 proteostasis 581:592 proteostasis 581:592 Therefore, we explored how N-glycosylation alters the protein homeostasis or proteostasis of wild-type (WT) and R345W F3 in ARPE-19 cells. 25389134 9 71 theme ER 1354:1355 arg1 lectins 1357:1363 the ER lectins 1350:1363 the ER lectins 1350:1363 Significantly more N249Q and N249Q/R345W F3 interacted with GRP94, while substantially less N249Q and N249Q/R345W interacted with the ER lectins than their N-glycosylated counterparts. 25389134 0 72 theme folding 59:65 arg1 pathways 67:74 two key folding pathways 51:74 two key folding pathways for R345W fibulin-3, a secreted protein associated with retinal degeneration 51:151 Genetic ablation of N-linked glycosylation reveals two key folding pathways for R345W fibulin-3, a secreted protein associated with retinal degeneration. 25389134 10 73 from reliance 1525:1532 arg1 GRP94 1537:1541 GRP94 1537:1541 GRP94 1537:1541 Inhibition of GRP94 ATPase activity reduced only N249Q/R345W F3 secretion (by 62%), demonstrating this variant's unique reliance on GRP94 for secretion. 25389134 8 74 theme F3 1176:1177 arg1 lectins 1123:1129 the ER lectins calnexin and calreticulin 1116:1155 the ER lectins calnexin and calreticulin 1116:1155 The endoplasmic reticulum (ER) chaperones GRP78 (glucose-regulated protein 78) and GRP94 (glucose-regulated protein 94), and the ER lectins calnexin and calreticulin were identified as F3 binding partners by immunoprecipitation. 25389134 8 74 theme F3 1176:1177 arg1 chaperones 1022:1031 The endoplasmic reticulum (ER) chaperones 991:1031 The endoplasmic reticulum (ER) chaperones GRP78 (glucose-regulated protein 78) and GRP94 (glucose-regulated protein 94) 991:1109 The endoplasmic reticulum (ER) chaperones GRP78 (glucose-regulated protein 78) and GRP94 (glucose-regulated protein 94), and the ER lectins calnexin and calreticulin were identified as F3 binding partners by immunoprecipitation. 25389134 8 74 theme F3 1176:1177 arg1 partners 1187:1194 F3 binding partners 1176:1194 F3 binding partners 1176:1194 The endoplasmic reticulum (ER) chaperones GRP78 (glucose-regulated protein 78) and GRP94 (glucose-regulated protein 94), and the ER lectins calnexin and calreticulin were identified as F3 binding partners by immunoprecipitation. 25389134 1 75 from mutation 163:170 arg1 N-glycoprotein 179:192 the N-glycoprotein 175:192 the N-glycoprotein 175:192 An R345W mutation in the N-glycoprotein, fibulin-3 (F3), results in inefficient F3 folding/secretion and higher intracellular F3 levels. 25389134 4 76 theme ARPE-19 628:634 arg1 cells 636:640 ARPE-19 cells 628:640 ARPE-19 cells 628:640 Therefore, we explored how N-glycosylation alters the protein homeostasis or proteostasis of wild-type (WT) and R345W F3 in ARPE-19 cells. 28054006 0 0 theme glycosylation 88:100 arg1 status 102:107 unique glycosylation status 81:107 unique glycosylation status on cellular proteins 81:128 Western blot data using two distinct anti-O-GlcNAc monoclonal antibodies showing unique glycosylation status on cellular proteins under 2-deoxy-d-glucose treatment. 28054006 2 1 theme 2DG 530:532 arg1 cells 571:575 2-deoxy-d-glucose (2DG)-treated human teratocarcinoma NCCIT cells 511:575 2-deoxy-d-glucose (2DG)-treated human teratocarcinoma NCCIT cells in support of the research article 511:610 This paper provides a data set relating to the O-GlcNAcylation of cellular proteins detected by RL2 and CTD110.6 antibodies, which are commonly used for detection of protein O-GlcNAcylation, in 2-deoxy-d-glucose (2DG)-treated human teratocarcinoma NCCIT cells in support of the research article entitled "A novel, promoter-based, target-specific assay identifies 2-deoxy-d-glucose as an inhibitor of globotriaosylceramide biosynthesis" (Okuda et al., 2009) [1]. 28054006 6 2 contain containing 1441:1450 arg1 proteins 1432:1439 the other proteins 1422:1439 the other proteins containing CTD110.6 epitopes 1422:1468 In contrast, the CTD110.6 epitope became detectable on Sp1 over 72 h after 2DG treatment, and then the other proteins containing CTD110.6 epitopes also appeared in the cell lysates and the anti-Sp1 antibody precipitates. 28054006 6 2 contain containing 1441:1450 arg2 epitopes 1461:1468 CTD110.6 epitopes 1452:1468 CTD110.6 epitopes 1452:1468 In contrast, the CTD110.6 epitope became detectable on Sp1 over 72 h after 2DG treatment, and then the other proteins containing CTD110.6 epitopes also appeared in the cell lysates and the anti-Sp1 antibody precipitates. 28054006 4 3 theme NCCIT 1128:1132 arg1 cells 1134:1138 NCCIT cells 1128:1138 NCCIT cells 1128:1138 The data in this paper complements this relationship by Western blotting and clearly showed that the 2DG treatment increased O-GlcNAcylation of cellular proteins in NCCIT cells, whereas the RL2 and CTD110.6 epitopes were detected in a different manner. 28054006 3 4 theme 2DG 830:832 arg1 effect 820:825 a suppressive effect 806:825 a suppressive effect of 2DG on an Sp1 target gene in NCCIT cells 806:869 The main article described a suppressive effect of 2DG on an Sp1 target gene in NCCIT cells and discussed the relationship between the effect of 2DG and O-GlcNAcylation status of Sp1. 28054006 3 5 theme target 844:849 arg1 gene 851:854 an Sp1 target gene 837:854 an Sp1 target gene in NCCIT cells 837:869 The main article described a suppressive effect of 2DG on an Sp1 target gene in NCCIT cells and discussed the relationship between the effect of 2DG and O-GlcNAcylation status of Sp1. 28054006 0 6 theme unique 81:86 arg1 status 102:107 unique glycosylation status 81:107 unique glycosylation status on cellular proteins 81:128 Western blot data using two distinct anti-O-GlcNAc monoclonal antibodies showing unique glycosylation status on cellular proteins under 2-deoxy-d-glucose treatment. 28054006 4 7 theme CTD110.6 1161:1168 arg1 epitopes 1170:1177 the RL2 and CTD110.6 epitopes 1149:1177 epitopes 1170:1177 The data in this paper complements this relationship by Western blotting and clearly showed that the 2DG treatment increased O-GlcNAcylation of cellular proteins in NCCIT cells, whereas the RL2 and CTD110.6 epitopes were detected in a different manner. 28054006 1 8 theme O-linked 189:196 arg1 O-GlcNAcylation 219:233 O-GlcNAcylation 219:233 O-GlcNAcylation 219:233 Protein modification by O-linked N-acetylglucosamine (O-GlcNAcylation) is one of the post transcriptional modifications occurring on cellular proteins. 28054006 1 8 theme O-linked 189:196 arg1 N-acetylglucosamine 198:216 O-linked N-acetylglucosamine 189:216 O-linked N-acetylglucosamine (O-GlcNAcylation) 189:234 Protein modification by O-linked N-acetylglucosamine (O-GlcNAcylation) is one of the post transcriptional modifications occurring on cellular proteins. 28054006 5 9 theme 2DG 1259:1261 arg1 treatment 1263:1271 2DG treatment 1259:1271 2DG treatment 1259:1271 The RL2 epitope was detected on Sp1 during 2DG treatment, and the level was transiently increased at 24 h. 28054006 1 10 theme cellular 298:305 arg1 proteins 307:314 cellular proteins 298:314 cellular proteins 298:314 Protein modification by O-linked N-acetylglucosamine (O-GlcNAcylation) is one of the post transcriptional modifications occurring on cellular proteins. 28054006 2 11 theme proteins 392:399 arg1 O-GlcNAcylation 364:378 the O-GlcNAcylation 360:378 the O-GlcNAcylation of cellular proteins detected by RL2 and CTD110.6 antibodies, which are commonly used for detection of protein O-GlcNAcylation, in 2-deoxy-d-glucose (2DG)-treated human teratocarcinoma NCCIT cells in support of the research article entitled "A novel, promoter-based, target-specific assay identifies 2-deoxy-d-glucose as an inhibitor of globotriaosylceramide biosynthesis" (Okuda et al., 2009) [1] 360:776 This paper provides a data set relating to the O-GlcNAcylation of cellular proteins detected by RL2 and CTD110.6 antibodies, which are commonly used for detection of protein O-GlcNAcylation, in 2-deoxy-d-glucose (2DG)-treated human teratocarcinoma NCCIT cells in support of the research article entitled "A novel, promoter-based, target-specific assay identifies 2-deoxy-d-glucose as an inhibitor of globotriaosylceramide biosynthesis" (Okuda et al., 2009) [1]. 28054006 4 12 theme 2DG 1064:1066 arg1 treatment 1068:1076 the 2DG treatment 1060:1076 the 2DG treatment 1060:1076 The data in this paper complements this relationship by Western blotting and clearly showed that the 2DG treatment increased O-GlcNAcylation of cellular proteins in NCCIT cells, whereas the RL2 and CTD110.6 epitopes were detected in a different manner. 28054006 2 13 theme NCCIT 565:569 arg1 cells 571:575 2-deoxy-d-glucose (2DG)-treated human teratocarcinoma NCCIT cells 511:575 2-deoxy-d-glucose (2DG)-treated human teratocarcinoma NCCIT cells in support of the research article 511:610 This paper provides a data set relating to the O-GlcNAcylation of cellular proteins detected by RL2 and CTD110.6 antibodies, which are commonly used for detection of protein O-GlcNAcylation, in 2-deoxy-d-glucose (2DG)-treated human teratocarcinoma NCCIT cells in support of the research article entitled "A novel, promoter-based, target-specific assay identifies 2-deoxy-d-glucose as an inhibitor of globotriaosylceramide biosynthesis" (Okuda et al., 2009) [1]. 28054006 6 14 theme antibody 1521:1528 arg1 precipitates 1530:1541 the anti-Sp1 antibody precipitates 1508:1541 the anti-Sp1 antibody precipitates 1508:1541 In contrast, the CTD110.6 epitope became detectable on Sp1 over 72 h after 2DG treatment, and then the other proteins containing CTD110.6 epitopes also appeared in the cell lysates and the anti-Sp1 antibody precipitates. 28054006 3 15 theme Sp1 840:842 arg1 gene 851:854 an Sp1 target gene 837:854 an Sp1 target gene in NCCIT cells 837:869 The main article described a suppressive effect of 2DG on an Sp1 target gene in NCCIT cells and discussed the relationship between the effect of 2DG and O-GlcNAcylation status of Sp1. 28054006 2 16 theme teratocarcinoma 549:563 arg1 cells 571:575 2-deoxy-d-glucose (2DG)-treated human teratocarcinoma NCCIT cells 511:575 2-deoxy-d-glucose (2DG)-treated human teratocarcinoma NCCIT cells in support of the research article 511:610 This paper provides a data set relating to the O-GlcNAcylation of cellular proteins detected by RL2 and CTD110.6 antibodies, which are commonly used for detection of protein O-GlcNAcylation, in 2-deoxy-d-glucose (2DG)-treated human teratocarcinoma NCCIT cells in support of the research article entitled "A novel, promoter-based, target-specific assay identifies 2-deoxy-d-glucose as an inhibitor of globotriaosylceramide biosynthesis" (Okuda et al., 2009) [1]. 28054006 5 17 theme RL2 1220:1222 arg1 epitope 1224:1230 The RL2 epitope 1216:1230 The RL2 epitope 1216:1230 The RL2 epitope was detected on Sp1 during 2DG treatment, and the level was transiently increased at 24 h. 28054006 3 18 theme 2DG 924:926 arg1 status 948:953 2DG and O-GlcNAcylation status 924:953 2DG and O-GlcNAcylation status of Sp1 924:960 The main article described a suppressive effect of 2DG on an Sp1 target gene in NCCIT cells and discussed the relationship between the effect of 2DG and O-GlcNAcylation status of Sp1. 28054006 0 19 theme cellular 112:119 arg1 proteins 121:128 cellular proteins 112:128 cellular proteins 112:128 Western blot data using two distinct anti-O-GlcNAc monoclonal antibodies showing unique glycosylation status on cellular proteins under 2-deoxy-d-glucose treatment. 28054006 0 20 theme distinct 28:35 arg1 antibodies 62:71 two distinct anti-O-GlcNAc monoclonal antibodies 24:71 two distinct anti-O-GlcNAc monoclonal antibodies showing unique glycosylation status on cellular proteins under 2-deoxy-d-glucose treatment 24:162 Western blot data using two distinct anti-O-GlcNAc monoclonal antibodies showing unique glycosylation status on cellular proteins under 2-deoxy-d-glucose treatment. 28054006 2 21 theme " 751:751 arg1 Okuda 754:758 Okuda 754:758 Okuda 754:758 This paper provides a data set relating to the O-GlcNAcylation of cellular proteins detected by RL2 and CTD110.6 antibodies, which are commonly used for detection of protein O-GlcNAcylation, in 2-deoxy-d-glucose (2DG)-treated human teratocarcinoma NCCIT cells in support of the research article entitled "A novel, promoter-based, target-specific assay identifies 2-deoxy-d-glucose as an inhibitor of globotriaosylceramide biosynthesis" (Okuda et al., 2009) [1]. 28054006 2 21 theme " 751:751 arg1 [1 774:775 globotriaosylceramide biosynthesis" (Okuda et al., 2009) [1 717:775 globotriaosylceramide biosynthesis" (Okuda et al., 2009) [1 717:775 This paper provides a data set relating to the O-GlcNAcylation of cellular proteins detected by RL2 and CTD110.6 antibodies, which are commonly used for detection of protein O-GlcNAcylation, in 2-deoxy-d-glucose (2DG)-treated human teratocarcinoma NCCIT cells in support of the research article entitled "A novel, promoter-based, target-specific assay identifies 2-deoxy-d-glucose as an inhibitor of globotriaosylceramide biosynthesis" (Okuda et al., 2009) [1]. 28054006 4 22 theme RL2 1153:1155 arg1 epitopes 1170:1177 the RL2 and CTD110.6 epitopes 1149:1177 epitopes 1170:1177 The data in this paper complements this relationship by Western blotting and clearly showed that the 2DG treatment increased O-GlcNAcylation of cellular proteins in NCCIT cells, whereas the RL2 and CTD110.6 epitopes were detected in a different manner. 28054006 0 23 theme blot 8:11 arg1 data 13:16 Western blot data 0:16 Western blot data 0:16 Western blot data using two distinct anti-O-GlcNAc monoclonal antibodies showing unique glycosylation status on cellular proteins under 2-deoxy-d-glucose treatment. 28054006 2 24 dep novel 624:628 arg1 target-specific 647:661 target-specific 647:661 target-specific 647:661 This paper provides a data set relating to the O-GlcNAcylation of cellular proteins detected by RL2 and CTD110.6 antibodies, which are commonly used for detection of protein O-GlcNAcylation, in 2-deoxy-d-glucose (2DG)-treated human teratocarcinoma NCCIT cells in support of the research article entitled "A novel, promoter-based, target-specific assay identifies 2-deoxy-d-glucose as an inhibitor of globotriaosylceramide biosynthesis" (Okuda et al., 2009) [1]. 28054006 2 24 dep novel 624:628 arg1 promoter-based 631:644 promoter-based 631:644 promoter-based 631:644 This paper provides a data set relating to the O-GlcNAcylation of cellular proteins detected by RL2 and CTD110.6 antibodies, which are commonly used for detection of protein O-GlcNAcylation, in 2-deoxy-d-glucose (2DG)-treated human teratocarcinoma NCCIT cells in support of the research article entitled "A novel, promoter-based, target-specific assay identifies 2-deoxy-d-glucose as an inhibitor of globotriaosylceramide biosynthesis" (Okuda et al., 2009) [1]. 28054006 2 25 theme biosynthesis 739:750 arg1 Okuda 754:758 Okuda 754:758 Okuda 754:758 This paper provides a data set relating to the O-GlcNAcylation of cellular proteins detected by RL2 and CTD110.6 antibodies, which are commonly used for detection of protein O-GlcNAcylation, in 2-deoxy-d-glucose (2DG)-treated human teratocarcinoma NCCIT cells in support of the research article entitled "A novel, promoter-based, target-specific assay identifies 2-deoxy-d-glucose as an inhibitor of globotriaosylceramide biosynthesis" (Okuda et al., 2009) [1]. 28054006 2 25 theme biosynthesis 739:750 arg1 [1 774:775 globotriaosylceramide biosynthesis" (Okuda et al., 2009) [1 717:775 globotriaosylceramide biosynthesis" (Okuda et al., 2009) [1 717:775 This paper provides a data set relating to the O-GlcNAcylation of cellular proteins detected by RL2 and CTD110.6 antibodies, which are commonly used for detection of protein O-GlcNAcylation, in 2-deoxy-d-glucose (2DG)-treated human teratocarcinoma NCCIT cells in support of the research article entitled "A novel, promoter-based, target-specific assay identifies 2-deoxy-d-glucose as an inhibitor of globotriaosylceramide biosynthesis" (Okuda et al., 2009) [1]. 28054006 0 26 theme Western 0:6 arg1 blot 8:11 Western blot 0:11 Western blot data 0:16 Western blot data using two distinct anti-O-GlcNAc monoclonal antibodies showing unique glycosylation status on cellular proteins under 2-deoxy-d-glucose treatment. 28054006 4 27 from data 967:970 arg1 paper 980:984 this paper 975:984 this paper 975:984 The data in this paper complements this relationship by Western blotting and clearly showed that the 2DG treatment increased O-GlcNAcylation of cellular proteins in NCCIT cells, whereas the RL2 and CTD110.6 epitopes were detected in a different manner. 28054006 2 28 theme globotriaosylceramide 717:737 arg1 Okuda 754:758 Okuda 754:758 Okuda 754:758 This paper provides a data set relating to the O-GlcNAcylation of cellular proteins detected by RL2 and CTD110.6 antibodies, which are commonly used for detection of protein O-GlcNAcylation, in 2-deoxy-d-glucose (2DG)-treated human teratocarcinoma NCCIT cells in support of the research article entitled "A novel, promoter-based, target-specific assay identifies 2-deoxy-d-glucose as an inhibitor of globotriaosylceramide biosynthesis" (Okuda et al., 2009) [1]. 28054006 2 28 theme globotriaosylceramide 717:737 arg1 [1 774:775 globotriaosylceramide biosynthesis" (Okuda et al., 2009) [1 717:775 globotriaosylceramide biosynthesis" (Okuda et al., 2009) [1 717:775 This paper provides a data set relating to the O-GlcNAcylation of cellular proteins detected by RL2 and CTD110.6 antibodies, which are commonly used for detection of protein O-GlcNAcylation, in 2-deoxy-d-glucose (2DG)-treated human teratocarcinoma NCCIT cells in support of the research article entitled "A novel, promoter-based, target-specific assay identifies 2-deoxy-d-glucose as an inhibitor of globotriaosylceramide biosynthesis" (Okuda et al., 2009) [1]. 28054006 3 29 theme status 948:953 arg1 effect 914:919 the effect 910:919 the effect of 2DG and O-GlcNAcylation status of Sp1 910:960 The main article described a suppressive effect of 2DG on an Sp1 target gene in NCCIT cells and discussed the relationship between the effect of 2DG and O-GlcNAcylation status of Sp1. 28054006 6 30 theme 2DG 1398:1400 arg1 treatment 1402:1410 2DG treatment 1398:1410 2DG treatment 1398:1410 In contrast, the CTD110.6 epitope became detectable on Sp1 over 72 h after 2DG treatment, and then the other proteins containing CTD110.6 epitopes also appeared in the cell lysates and the anti-Sp1 antibody precipitates. 28054006 3 31 theme main 783:786 arg1 article 788:794 The main article 779:794 The main article 779:794 The main article described a suppressive effect of 2DG on an Sp1 target gene in NCCIT cells and discussed the relationship between the effect of 2DG and O-GlcNAcylation status of Sp1. 28054006 0 32 theme 2-deoxy-d-glucose 136:152 arg1 treatment 154:162 2-deoxy-d-glucose treatment 136:162 2-deoxy-d-glucose treatment 136:162 Western blot data using two distinct anti-O-GlcNAc monoclonal antibodies showing unique glycosylation status on cellular proteins under 2-deoxy-d-glucose treatment. 28054006 4 33 theme proteins 1116:1123 arg1 O-GlcNAcylation 1088:1102 O-GlcNAcylation 1088:1102 O-GlcNAcylation of cellular proteins in NCCIT cells 1088:1138 The data in this paper complements this relationship by Western blotting and clearly showed that the 2DG treatment increased O-GlcNAcylation of cellular proteins in NCCIT cells, whereas the RL2 and CTD110.6 epitopes were detected in a different manner. 28054006 2 34 dep assay 663:667 arg1 identifies 669:678 identifies 669:678 identifies 2-deoxy-d-glucose as an inhibitor of globotriaosylceramide biosynthesis" (Okuda et al., 2009) [1 669:775 This paper provides a data set relating to the O-GlcNAcylation of cellular proteins detected by RL2 and CTD110.6 antibodies, which are commonly used for detection of protein O-GlcNAcylation, in 2-deoxy-d-glucose (2DG)-treated human teratocarcinoma NCCIT cells in support of the research article entitled "A novel, promoter-based, target-specific assay identifies 2-deoxy-d-glucose as an inhibitor of globotriaosylceramide biosynthesis" (Okuda et al., 2009) [1]. 28054006 1 35 link O-linked 189:196 arg1 O-GlcNAcylation 219:233 O-GlcNAcylation 219:233 O-GlcNAcylation 219:233 Protein modification by O-linked N-acetylglucosamine (O-GlcNAcylation) is one of the post transcriptional modifications occurring on cellular proteins. 28054006 1 35 link O-linked 189:196 arg1 N-acetylglucosamine 198:216 O-linked N-acetylglucosamine 189:216 O-linked N-acetylglucosamine (O-GlcNAcylation) 189:234 Protein modification by O-linked N-acetylglucosamine (O-GlcNAcylation) is one of the post transcriptional modifications occurring on cellular proteins. 28054006 2 36 theme data 339:342 arg1 set 344:346 a data set 337:346 a data set relating to the O-GlcNAcylation of cellular proteins detected by RL2 and CTD110.6 antibodies, which are commonly used for detection of protein O-GlcNAcylation, in 2-deoxy-d-glucose (2DG)-treated human teratocarcinoma NCCIT cells in support of the research article entitled "A novel, promoter-based, target-specific assay identifies 2-deoxy-d-glucose as an inhibitor of globotriaosylceramide biosynthesis" (Okuda et al., 2009) [1] 337:776 This paper provides a data set relating to the O-GlcNAcylation of cellular proteins detected by RL2 and CTD110.6 antibodies, which are commonly used for detection of protein O-GlcNAcylation, in 2-deoxy-d-glucose (2DG)-treated human teratocarcinoma NCCIT cells in support of the research article entitled "A novel, promoter-based, target-specific assay identifies 2-deoxy-d-glucose as an inhibitor of globotriaosylceramide biosynthesis" (Okuda et al., 2009) [1]. 28054006 2 37 theme 2-deoxy-d-glucose 511:527 arg1 cells 571:575 2-deoxy-d-glucose (2DG)-treated human teratocarcinoma NCCIT cells 511:575 2-deoxy-d-glucose (2DG)-treated human teratocarcinoma NCCIT cells in support of the research article 511:610 This paper provides a data set relating to the O-GlcNAcylation of cellular proteins detected by RL2 and CTD110.6 antibodies, which are commonly used for detection of protein O-GlcNAcylation, in 2-deoxy-d-glucose (2DG)-treated human teratocarcinoma NCCIT cells in support of the research article entitled "A novel, promoter-based, target-specific assay identifies 2-deoxy-d-glucose as an inhibitor of globotriaosylceramide biosynthesis" (Okuda et al., 2009) [1]. 28054006 6 38 theme anti-Sp1 1512:1519 arg1 precipitates 1530:1541 the anti-Sp1 antibody precipitates 1508:1541 the anti-Sp1 antibody precipitates 1508:1541 In contrast, the CTD110.6 epitope became detectable on Sp1 over 72 h after 2DG treatment, and then the other proteins containing CTD110.6 epitopes also appeared in the cell lysates and the anti-Sp1 antibody precipitates. 28054006 6 39 theme other 1426:1430 arg1 proteins 1432:1439 the other proteins 1422:1439 the other proteins containing CTD110.6 epitopes 1422:1468 In contrast, the CTD110.6 epitope became detectable on Sp1 over 72 h after 2DG treatment, and then the other proteins containing CTD110.6 epitopes also appeared in the cell lysates and the anti-Sp1 antibody precipitates. 28054006 3 40 theme O-GlcNAcylation 932:946 arg1 status 948:953 2DG and O-GlcNAcylation status 924:953 2DG and O-GlcNAcylation status of Sp1 924:960 The main article described a suppressive effect of 2DG on an Sp1 target gene in NCCIT cells and discussed the relationship between the effect of 2DG and O-GlcNAcylation status of Sp1. 28054006 3 41 from gene 851:854 arg1 cells 865:869 NCCIT cells 859:869 NCCIT cells 859:869 The main article described a suppressive effect of 2DG on an Sp1 target gene in NCCIT cells and discussed the relationship between the effect of 2DG and O-GlcNAcylation status of Sp1. 28054006 2 42 theme human 543:547 arg1 cells 571:575 2-deoxy-d-glucose (2DG)-treated human teratocarcinoma NCCIT cells 511:575 2-deoxy-d-glucose (2DG)-treated human teratocarcinoma NCCIT cells in support of the research article 511:610 This paper provides a data set relating to the O-GlcNAcylation of cellular proteins detected by RL2 and CTD110.6 antibodies, which are commonly used for detection of protein O-GlcNAcylation, in 2-deoxy-d-glucose (2DG)-treated human teratocarcinoma NCCIT cells in support of the research article entitled "A novel, promoter-based, target-specific assay identifies 2-deoxy-d-glucose as an inhibitor of globotriaosylceramide biosynthesis" (Okuda et al., 2009) [1]. 28054006 0 43 theme monoclonal 51:60 arg1 antibodies 62:71 two distinct anti-O-GlcNAc monoclonal antibodies 24:71 two distinct anti-O-GlcNAc monoclonal antibodies showing unique glycosylation status on cellular proteins under 2-deoxy-d-glucose treatment 24:162 Western blot data using two distinct anti-O-GlcNAc monoclonal antibodies showing unique glycosylation status on cellular proteins under 2-deoxy-d-glucose treatment. 28054006 3 44 theme suppressive 808:818 arg1 effect 820:825 a suppressive effect 806:825 a suppressive effect of 2DG on an Sp1 target gene in NCCIT cells 806:869 The main article described a suppressive effect of 2DG on an Sp1 target gene in NCCIT cells and discussed the relationship between the effect of 2DG and O-GlcNAcylation status of Sp1. 28054006 3 45 from effect 820:825 arg1 gene 851:854 an Sp1 target gene 837:854 an Sp1 target gene in NCCIT cells 837:869 The main article described a suppressive effect of 2DG on an Sp1 target gene in NCCIT cells and discussed the relationship between the effect of 2DG and O-GlcNAcylation status of Sp1. 28054006 2 46 theme cellular 383:390 arg1 proteins 392:399 cellular proteins 383:399 cellular proteins 383:399 This paper provides a data set relating to the O-GlcNAcylation of cellular proteins detected by RL2 and CTD110.6 antibodies, which are commonly used for detection of protein O-GlcNAcylation, in 2-deoxy-d-glucose (2DG)-treated human teratocarcinoma NCCIT cells in support of the research article entitled "A novel, promoter-based, target-specific assay identifies 2-deoxy-d-glucose as an inhibitor of globotriaosylceramide biosynthesis" (Okuda et al., 2009) [1]. 28054006 0 47 theme anti-O-GlcNAc 37:49 arg1 antibodies 62:71 two distinct anti-O-GlcNAc monoclonal antibodies 24:71 two distinct anti-O-GlcNAc monoclonal antibodies showing unique glycosylation status on cellular proteins under 2-deoxy-d-glucose treatment 24:162 Western blot data using two distinct anti-O-GlcNAc monoclonal antibodies showing unique glycosylation status on cellular proteins under 2-deoxy-d-glucose treatment. 28054006 2 48 theme O-GlcNAcylation 491:505 arg1 detection 470:478 detection 470:478 detection of protein O-GlcNAcylation 470:505 This paper provides a data set relating to the O-GlcNAcylation of cellular proteins detected by RL2 and CTD110.6 antibodies, which are commonly used for detection of protein O-GlcNAcylation, in 2-deoxy-d-glucose (2DG)-treated human teratocarcinoma NCCIT cells in support of the research article entitled "A novel, promoter-based, target-specific assay identifies 2-deoxy-d-glucose as an inhibitor of globotriaosylceramide biosynthesis" (Okuda et al., 2009) [1]. 28054006 5 49 located detected 1236:1243 arg1 Sp1 1248:1250 Sp1 1248:1250 Sp1 1248:1250 The RL2 epitope was detected on Sp1 during 2DG treatment, and the level was transiently increased at 24 h. 28054006 5 49 located detected 1236:1243 arg2 epitope 1224:1230 The RL2 epitope 1216:1230 The RL2 epitope 1216:1230 The RL2 epitope was detected on Sp1 during 2DG treatment, and the level was transiently increased at 24 h. 28054006 3 50 theme Sp1 958:960 arg1 status 948:953 2DG and O-GlcNAcylation status 924:953 2DG and O-GlcNAcylation status of Sp1 924:960 The main article described a suppressive effect of 2DG on an Sp1 target gene in NCCIT cells and discussed the relationship between the effect of 2DG and O-GlcNAcylation status of Sp1. 28054006 2 51 theme novel 624:628 arg1 assay 663:667 A novel, promoter-based, target-specific assay 622:667 "A novel, promoter-based, target-specific assay identifies 2-deoxy-d-glucose as an inhibitor of globotriaosylceramide biosynthesis" (Okuda et al., 2009) [1] 621:776 This paper provides a data set relating to the O-GlcNAcylation of cellular proteins detected by RL2 and CTD110.6 antibodies, which are commonly used for detection of protein O-GlcNAcylation, in 2-deoxy-d-glucose (2DG)-treated human teratocarcinoma NCCIT cells in support of the research article entitled "A novel, promoter-based, target-specific assay identifies 2-deoxy-d-glucose as an inhibitor of globotriaosylceramide biosynthesis" (Okuda et al., 2009) [1]. 28054006 2 52 theme article 604:610 arg1 support 580:586 support 580:586 support of the research article 580:610 This paper provides a data set relating to the O-GlcNAcylation of cellular proteins detected by RL2 and CTD110.6 antibodies, which are commonly used for detection of protein O-GlcNAcylation, in 2-deoxy-d-glucose (2DG)-treated human teratocarcinoma NCCIT cells in support of the research article entitled "A novel, promoter-based, target-specific assay identifies 2-deoxy-d-glucose as an inhibitor of globotriaosylceramide biosynthesis" (Okuda et al., 2009) [1]. 28054006 2 53 used used 461:464 arg2 proteins 392:399 cellular proteins 383:399 cellular proteins 383:399 This paper provides a data set relating to the O-GlcNAcylation of cellular proteins detected by RL2 and CTD110.6 antibodies, which are commonly used for detection of protein O-GlcNAcylation, in 2-deoxy-d-glucose (2DG)-treated human teratocarcinoma NCCIT cells in support of the research article entitled "A novel, promoter-based, target-specific assay identifies 2-deoxy-d-glucose as an inhibitor of globotriaosylceramide biosynthesis" (Okuda et al., 2009) [1]. 28054006 4 54 from O-GlcNAcylation 1088:1102 arg1 cells 1134:1138 NCCIT cells 1128:1138 NCCIT cells 1128:1138 The data in this paper complements this relationship by Western blotting and clearly showed that the 2DG treatment increased O-GlcNAcylation of cellular proteins in NCCIT cells, whereas the RL2 and CTD110.6 epitopes were detected in a different manner. 28054006 4 55 theme different 1198:1206 arg1 manner 1208:1213 a different manner 1196:1213 a different manner 1196:1213 The data in this paper complements this relationship by Western blotting and clearly showed that the 2DG treatment increased O-GlcNAcylation of cellular proteins in NCCIT cells, whereas the RL2 and CTD110.6 epitopes were detected in a different manner. 28054006 1 56 theme post 250:253 arg1 modifications 271:283 the post transcriptional modifications 246:283 the post transcriptional modifications occurring on cellular proteins 246:314 Protein modification by O-linked N-acetylglucosamine (O-GlcNAcylation) is one of the post transcriptional modifications occurring on cellular proteins. 28054006 2 57 theme research 595:602 arg1 article 604:610 the research article 591:610 the research article 591:610 This paper provides a data set relating to the O-GlcNAcylation of cellular proteins detected by RL2 and CTD110.6 antibodies, which are commonly used for detection of protein O-GlcNAcylation, in 2-deoxy-d-glucose (2DG)-treated human teratocarcinoma NCCIT cells in support of the research article entitled "A novel, promoter-based, target-specific assay identifies 2-deoxy-d-glucose as an inhibitor of globotriaosylceramide biosynthesis" (Okuda et al., 2009) [1]. 28054006 2 58 from cells 571:575 arg1 support 580:586 support 580:586 support of the research article 580:610 This paper provides a data set relating to the O-GlcNAcylation of cellular proteins detected by RL2 and CTD110.6 antibodies, which are commonly used for detection of protein O-GlcNAcylation, in 2-deoxy-d-glucose (2DG)-treated human teratocarcinoma NCCIT cells in support of the research article entitled "A novel, promoter-based, target-specific assay identifies 2-deoxy-d-glucose as an inhibitor of globotriaosylceramide biosynthesis" (Okuda et al., 2009) [1]. 28054006 2 59 theme [1 774:775 arg1 2-deoxy-d-glucose 680:696 2-deoxy-d-glucose 680:696 2-deoxy-d-glucose 680:696 This paper provides a data set relating to the O-GlcNAcylation of cellular proteins detected by RL2 and CTD110.6 antibodies, which are commonly used for detection of protein O-GlcNAcylation, in 2-deoxy-d-glucose (2DG)-treated human teratocarcinoma NCCIT cells in support of the research article entitled "A novel, promoter-based, target-specific assay identifies 2-deoxy-d-glucose as an inhibitor of globotriaosylceramide biosynthesis" (Okuda et al., 2009) [1]. 28054006 2 59 theme [1 774:775 arg1 inhibitor 704:712 an inhibitor 701:712 an inhibitor of globotriaosylceramide biosynthesis" (Okuda et al., 2009) [1 701:775 This paper provides a data set relating to the O-GlcNAcylation of cellular proteins detected by RL2 and CTD110.6 antibodies, which are commonly used for detection of protein O-GlcNAcylation, in 2-deoxy-d-glucose (2DG)-treated human teratocarcinoma NCCIT cells in support of the research article entitled "A novel, promoter-based, target-specific assay identifies 2-deoxy-d-glucose as an inhibitor of globotriaosylceramide biosynthesis" (Okuda et al., 2009) [1]. 28054006 6 60 theme cell 1491:1494 arg1 lysates 1496:1502 the cell lysates 1487:1502 the cell lysates 1487:1502 In contrast, the CTD110.6 epitope became detectable on Sp1 over 72 h after 2DG treatment, and then the other proteins containing CTD110.6 epitopes also appeared in the cell lysates and the anti-Sp1 antibody precipitates. 28054006 4 61 theme cellular 1107:1114 arg1 proteins 1116:1123 cellular proteins 1107:1123 cellular proteins 1107:1123 The data in this paper complements this relationship by Western blotting and clearly showed that the 2DG treatment increased O-GlcNAcylation of cellular proteins in NCCIT cells, whereas the RL2 and CTD110.6 epitopes were detected in a different manner. 28054006 1 62 theme transcriptional 255:269 arg1 modifications 271:283 the post transcriptional modifications 246:283 the post transcriptional modifications occurring on cellular proteins 246:314 Protein modification by O-linked N-acetylglucosamine (O-GlcNAcylation) is one of the post transcriptional modifications occurring on cellular proteins. 28054006 2 63 theme -treated 534:541 arg1 cells 571:575 2-deoxy-d-glucose (2DG)-treated human teratocarcinoma NCCIT cells 511:575 2-deoxy-d-glucose (2DG)-treated human teratocarcinoma NCCIT cells in support of the research article 511:610 This paper provides a data set relating to the O-GlcNAcylation of cellular proteins detected by RL2 and CTD110.6 antibodies, which are commonly used for detection of protein O-GlcNAcylation, in 2-deoxy-d-glucose (2DG)-treated human teratocarcinoma NCCIT cells in support of the research article entitled "A novel, promoter-based, target-specific assay identifies 2-deoxy-d-glucose as an inhibitor of globotriaosylceramide biosynthesis" (Okuda et al., 2009) [1]. 28054006 0 64 from status 102:107 arg1 proteins 121:128 cellular proteins 112:128 cellular proteins 112:128 Western blot data using two distinct anti-O-GlcNAc monoclonal antibodies showing unique glycosylation status on cellular proteins under 2-deoxy-d-glucose treatment. 28054006 4 65 located detected 1184:1191 arg1 manner 1208:1213 a different manner 1196:1213 a different manner 1196:1213 The data in this paper complements this relationship by Western blotting and clearly showed that the 2DG treatment increased O-GlcNAcylation of cellular proteins in NCCIT cells, whereas the RL2 and CTD110.6 epitopes were detected in a different manner. 28054006 4 65 located detected 1184:1191 arg2 epitopes 1170:1177 the RL2 and CTD110.6 epitopes 1149:1177 epitopes 1170:1177 The data in this paper complements this relationship by Western blotting and clearly showed that the 2DG treatment increased O-GlcNAcylation of cellular proteins in NCCIT cells, whereas the RL2 and CTD110.6 epitopes were detected in a different manner. 28054006 1 66 theme Protein 165:171 arg1 modification 173:184 Protein modification 165:184 Protein modification by O-linked N-acetylglucosamine (O-GlcNAcylation) 165:234 Protein modification by O-linked N-acetylglucosamine (O-GlcNAcylation) is one of the post transcriptional modifications occurring on cellular proteins. 28054006 3 67 theme NCCIT 859:863 arg1 cells 865:869 NCCIT cells 859:869 NCCIT cells 859:869 The main article described a suppressive effect of 2DG on an Sp1 target gene in NCCIT cells and discussed the relationship between the effect of 2DG and O-GlcNAcylation status of Sp1. 28054006 1 68 theme modifications 271:283 arg1 modifications 271:283 the post transcriptional modifications 246:283 the post transcriptional modifications occurring on cellular proteins 246:314 Protein modification by O-linked N-acetylglucosamine (O-GlcNAcylation) is one of the post transcriptional modifications occurring on cellular proteins. 28054006 1 68 theme modifications 271:283 arg1 one 239:241 one 239:241 one 239:241 Protein modification by O-linked N-acetylglucosamine (O-GlcNAcylation) is one of the post transcriptional modifications occurring on cellular proteins. 28054006 4 69 theme Western 1019:1025 arg1 blotting 1027:1034 Western blotting 1019:1034 Western blotting 1019:1034 The data in this paper complements this relationship by Western blotting and clearly showed that the 2DG treatment increased O-GlcNAcylation of cellular proteins in NCCIT cells, whereas the RL2 and CTD110.6 epitopes were detected in a different manner. 28054006 2 70 theme protein 483:489 arg1 O-GlcNAcylation 491:505 protein O-GlcNAcylation 483:505 protein O-GlcNAcylation 483:505 This paper provides a data set relating to the O-GlcNAcylation of cellular proteins detected by RL2 and CTD110.6 antibodies, which are commonly used for detection of protein O-GlcNAcylation, in 2-deoxy-d-glucose (2DG)-treated human teratocarcinoma NCCIT cells in support of the research article entitled "A novel, promoter-based, target-specific assay identifies 2-deoxy-d-glucose as an inhibitor of globotriaosylceramide biosynthesis" (Okuda et al., 2009) [1]. 23420653 0 0 theme muscular 83:90 arg1 dystrophy 92:100 congenital muscular dystrophy 72:100 congenital muscular dystrophy 72:100 Elevated serum creatine kinase and small cerebellum prompt diagnosis of congenital muscular dystrophy due to FKRP mutations. 23420653 3 1 theme widening 672:679 arg1 suggestive 658:667 suggestive 658:667 suggestive 658:667 This article reports on a Moroccan infant who presented at birth with moderate floppiness, high serum creatine kinase (CK) levels, and brain ultrasonograph suggestive of widening of the posterior fossa. 23420653 4 2 from variant 850:856 arg1 FKRP 861:864 FKRP 861:864 FKRP 861:864 Muscle biopsy displayed moderate dystrophic pattern with complete absence of α-distroglycan and genetic studies identified a homozygous missense variant in FKRP. 23420653 0 3 theme congenital 72:81 arg1 dystrophy 92:100 congenital muscular dystrophy 72:100 congenital muscular dystrophy 72:100 Elevated serum creatine kinase and small cerebellum prompt diagnosis of congenital muscular dystrophy due to FKRP mutations. 23420653 4 4 theme complete 762:769 arg1 absence 771:777 complete absence 762:777 complete absence of α-distroglycan 762:795 Muscle biopsy displayed moderate dystrophic pattern with complete absence of α-distroglycan and genetic studies identified a homozygous missense variant in FKRP. 23420653 2 5 theme girdle 325:330 arg1 dystrophy 341:349 a limb girdle muscular dystrophy 2I 318:352 a limb girdle muscular dystrophy 2I (LGMD2I) 318:361 Mutations in the FKRP gene cause a spectrum of diseases ranging from a limb girdle muscular dystrophy 2I (LGMD2I), to severe Walker-Warburg or muscle-eye-brain forms and a congenital muscular dystrophy (with or without mental retardation) termed MDC1C. 23420653 2 5 theme girdle 325:330 arg1 LGMD2I 355:360 LGMD2I 355:360 LGMD2I 355:360 Mutations in the FKRP gene cause a spectrum of diseases ranging from a limb girdle muscular dystrophy 2I (LGMD2I), to severe Walker-Warburg or muscle-eye-brain forms and a congenital muscular dystrophy (with or without mental retardation) termed MDC1C. 23420653 3 6 theme creatine 604:611 arg1 CK 621:622 CK 621:622 CK 621:622 This article reports on a Moroccan infant who presented at birth with moderate floppiness, high serum creatine kinase (CK) levels, and brain ultrasonograph suggestive of widening of the posterior fossa. 23420653 3 6 theme creatine 604:611 arg1 kinase 613:618 serum creatine kinase 598:618 high serum creatine kinase (CK) levels 593:630 This article reports on a Moroccan infant who presented at birth with moderate floppiness, high serum creatine kinase (CK) levels, and brain ultrasonograph suggestive of widening of the posterior fossa. 23420653 4 7 theme dystrophic 738:747 arg1 pattern 749:755 moderate dystrophic pattern 729:755 moderate dystrophic pattern 729:755 Muscle biopsy displayed moderate dystrophic pattern with complete absence of α-distroglycan and genetic studies identified a homozygous missense variant in FKRP. 23420653 0 8 theme dystrophy 92:100 arg1 diagnosis 59:67 diagnosis 59:67 diagnosis of congenital muscular dystrophy due to FKRP mutations 59:122 Elevated serum creatine kinase and small cerebellum prompt diagnosis of congenital muscular dystrophy due to FKRP mutations. 23420653 3 9 theme posterior 688:696 arg1 fossa 698:702 the posterior fossa 684:702 the posterior fossa 684:702 This article reports on a Moroccan infant who presented at birth with moderate floppiness, high serum creatine kinase (CK) levels, and brain ultrasonograph suggestive of widening of the posterior fossa. 23420653 1 10 link O-linked 203:210 arg1 glycosylation 212:224 O-linked glycosylation 203:224 O-linked glycosylation of the α-dystroglycan 203:246 Fukutin-related protein (FKRP) is a putative glycosyltransferase that mediate O-linked glycosylation of the α-dystroglycan. 23420653 3 11 theme Moroccan 528:535 arg1 infant 537:542 a Moroccan infant 526:542 a Moroccan infant who presented at birth with moderate floppiness, high serum creatine kinase (CK) levels, and brain ultrasonograph suggestive of widening of the posterior fossa 526:702 This article reports on a Moroccan infant who presented at birth with moderate floppiness, high serum creatine kinase (CK) levels, and brain ultrasonograph suggestive of widening of the posterior fossa. 23420653 0 12 theme FKRP 109:112 arg1 mutations 114:122 FKRP mutations 109:122 FKRP mutations 109:122 Elevated serum creatine kinase and small cerebellum prompt diagnosis of congenital muscular dystrophy due to FKRP mutations. 23420653 3 13 theme fossa 698:702 arg1 widening 672:679 widening 672:679 widening of the posterior fossa 672:702 This article reports on a Moroccan infant who presented at birth with moderate floppiness, high serum creatine kinase (CK) levels, and brain ultrasonograph suggestive of widening of the posterior fossa. 23420653 4 14 theme homozygous 830:839 arg1 variant 850:856 a homozygous missense variant 828:856 a homozygous missense variant in FKRP 828:864 Muscle biopsy displayed moderate dystrophic pattern with complete absence of α-distroglycan and genetic studies identified a homozygous missense variant in FKRP. 23420653 5 15 theme small 966:970 arg1 cerebellum 972:981 small cerebellum 966:981 small cerebellum 966:981 Mutations in FKRP should be looked for in forms of neonatal-onset hyperCKaemia with floppiness and small cerebellum. 23420653 3 16 attach presented 548:556 arg1 birth 561:565 birth 561:565 birth 561:565 This article reports on a Moroccan infant who presented at birth with moderate floppiness, high serum creatine kinase (CK) levels, and brain ultrasonograph suggestive of widening of the posterior fossa. 23420653 3 16 attach presented 548:556 arg2 infant 537:542 a Moroccan infant 526:542 a Moroccan infant who presented at birth with moderate floppiness, high serum creatine kinase (CK) levels, and brain ultrasonograph suggestive of widening of the posterior fossa 526:702 This article reports on a Moroccan infant who presented at birth with moderate floppiness, high serum creatine kinase (CK) levels, and brain ultrasonograph suggestive of widening of the posterior fossa. 23420653 2 17 theme Walker-Warburg 374:387 arg1 forms 409:413 severe Walker-Warburg or muscle-eye-brain forms 367:413 severe Walker-Warburg or muscle-eye-brain forms 367:413 Mutations in the FKRP gene cause a spectrum of diseases ranging from a limb girdle muscular dystrophy 2I (LGMD2I), to severe Walker-Warburg or muscle-eye-brain forms and a congenital muscular dystrophy (with or without mental retardation) termed MDC1C. 23420653 2 18 theme muscular 432:439 arg1 dystrophy 441:449 a congenital muscular dystrophy 419:449 a congenital muscular dystrophy (with or without mental retardation) 419:486 Mutations in the FKRP gene cause a spectrum of diseases ranging from a limb girdle muscular dystrophy 2I (LGMD2I), to severe Walker-Warburg or muscle-eye-brain forms and a congenital muscular dystrophy (with or without mental retardation) termed MDC1C. 23420653 2 19 from Mutations 249:257 arg1 gene 271:274 the FKRP gene 262:274 the FKRP gene 262:274 Mutations in the FKRP gene cause a spectrum of diseases ranging from a limb girdle muscular dystrophy 2I (LGMD2I), to severe Walker-Warburg or muscle-eye-brain forms and a congenital muscular dystrophy (with or without mental retardation) termed MDC1C. 23420653 1 20 theme putative 161:168 arg1 glycosyltransferase 170:188 a putative glycosyltransferase 159:188 a putative glycosyltransferase that mediate O-linked glycosylation of the α-dystroglycan 159:246 Fukutin-related protein (FKRP) is a putative glycosyltransferase that mediate O-linked glycosylation of the α-dystroglycan. 23420653 1 20 theme putative 161:168 arg1 protein 141:147 Fukutin-related protein 125:147 Fukutin-related protein (FKRP) 125:154 Fukutin-related protein (FKRP) is a putative glycosyltransferase that mediate O-linked glycosylation of the α-dystroglycan. 23420653 0 21 theme serum 9:13 arg1 kinase 24:29 Elevated serum creatine kinase 0:29 Elevated serum creatine kinase 0:29 Elevated serum creatine kinase and small cerebellum prompt diagnosis of congenital muscular dystrophy due to FKRP mutations. 23420653 2 22 theme mental 468:473 arg1 retardation 475:485 mental retardation 468:485 mental retardation 468:485 Mutations in the FKRP gene cause a spectrum of diseases ranging from a limb girdle muscular dystrophy 2I (LGMD2I), to severe Walker-Warburg or muscle-eye-brain forms and a congenital muscular dystrophy (with or without mental retardation) termed MDC1C. 23420653 4 23 theme Muscle 705:710 arg1 biopsy 712:717 Muscle biopsy 705:717 Muscle biopsy 705:717 Muscle biopsy displayed moderate dystrophic pattern with complete absence of α-distroglycan and genetic studies identified a homozygous missense variant in FKRP. 23420653 0 24 theme Elevated 0:7 arg1 kinase 24:29 Elevated serum creatine kinase 0:29 Elevated serum creatine kinase 0:29 Elevated serum creatine kinase and small cerebellum prompt diagnosis of congenital muscular dystrophy due to FKRP mutations. 23420653 1 25 gly glycosylation 212:224 arg1 α-dystroglycan 233:246 the α-dystroglycan 229:246 the α-dystroglycan 229:246 Fukutin-related protein (FKRP) is a putative glycosyltransferase that mediate O-linked glycosylation of the α-dystroglycan. 23420653 5 26 theme neonatal-onset 918:931 arg1 hyperCKaemia 933:944 neonatal-onset hyperCKaemia 918:944 neonatal-onset hyperCKaemia with floppiness and small cerebellum 918:981 Mutations in FKRP should be looked for in forms of neonatal-onset hyperCKaemia with floppiness and small cerebellum. 23420653 2 27 theme congenital 421:430 arg1 dystrophy 441:449 a congenital muscular dystrophy 419:449 a congenital muscular dystrophy (with or without mental retardation) 419:486 Mutations in the FKRP gene cause a spectrum of diseases ranging from a limb girdle muscular dystrophy 2I (LGMD2I), to severe Walker-Warburg or muscle-eye-brain forms and a congenital muscular dystrophy (with or without mental retardation) termed MDC1C. 23420653 5 28 theme hyperCKaemia 933:944 arg1 forms 909:913 forms 909:913 forms of neonatal-onset hyperCKaemia with floppiness and small cerebellum 909:981 Mutations in FKRP should be looked for in forms of neonatal-onset hyperCKaemia with floppiness and small cerebellum. 23420653 4 29 theme genetic 801:807 arg1 studies 809:815 genetic studies 801:815 genetic studies 801:815 Muscle biopsy displayed moderate dystrophic pattern with complete absence of α-distroglycan and genetic studies identified a homozygous missense variant in FKRP. 23420653 0 30 theme creatine 15:22 arg1 kinase 24:29 Elevated serum creatine kinase 0:29 Elevated serum creatine kinase 0:29 Elevated serum creatine kinase and small cerebellum prompt diagnosis of congenital muscular dystrophy due to FKRP mutations. 23420653 2 31 theme diseases 296:303 arg1 spectrum 284:291 a spectrum 282:291 a spectrum of diseases ranging from a limb girdle muscular dystrophy 2I (LGMD2I), to severe Walker-Warburg or muscle-eye-brain forms and a congenital muscular dystrophy (with or without mental retardation) termed MDC1C 282:499 Mutations in the FKRP gene cause a spectrum of diseases ranging from a limb girdle muscular dystrophy 2I (LGMD2I), to severe Walker-Warburg or muscle-eye-brain forms and a congenital muscular dystrophy (with or without mental retardation) termed MDC1C. 23420653 1 32 theme O-linked 203:210 arg1 glycosylation 212:224 O-linked glycosylation 203:224 O-linked glycosylation of the α-dystroglycan 203:246 Fukutin-related protein (FKRP) is a putative glycosyltransferase that mediate O-linked glycosylation of the α-dystroglycan. 23420653 0 33 theme small 35:39 arg1 cerebellum 41:50 small cerebellum 35:50 small cerebellum 35:50 Elevated serum creatine kinase and small cerebellum prompt diagnosis of congenital muscular dystrophy due to FKRP mutations. 23420653 3 34 theme moderate 572:579 arg1 floppiness 581:590 moderate floppiness 572:590 moderate floppiness 572:590 This article reports on a Moroccan infant who presented at birth with moderate floppiness, high serum creatine kinase (CK) levels, and brain ultrasonograph suggestive of widening of the posterior fossa. 23420653 2 35 theme muscle-eye-brain 392:407 arg1 forms 409:413 severe Walker-Warburg or muscle-eye-brain forms 367:413 severe Walker-Warburg or muscle-eye-brain forms 367:413 Mutations in the FKRP gene cause a spectrum of diseases ranging from a limb girdle muscular dystrophy 2I (LGMD2I), to severe Walker-Warburg or muscle-eye-brain forms and a congenital muscular dystrophy (with or without mental retardation) termed MDC1C. 23420653 3 36 theme kinase 613:618 arg1 levels 625:630 high serum creatine kinase (CK) levels 593:630 high serum creatine kinase (CK) levels 593:630 This article reports on a Moroccan infant who presented at birth with moderate floppiness, high serum creatine kinase (CK) levels, and brain ultrasonograph suggestive of widening of the posterior fossa. 23420653 4 37 theme moderate 729:736 arg1 pattern 749:755 moderate dystrophic pattern 729:755 moderate dystrophic pattern 729:755 Muscle biopsy displayed moderate dystrophic pattern with complete absence of α-distroglycan and genetic studies identified a homozygous missense variant in FKRP. 23420653 4 38 theme missense 841:848 arg1 variant 850:856 a homozygous missense variant 828:856 a homozygous missense variant in FKRP 828:864 Muscle biopsy displayed moderate dystrophic pattern with complete absence of α-distroglycan and genetic studies identified a homozygous missense variant in FKRP. 23420653 3 39 theme suggestive 658:667 arg1 ultrasonograph 643:656 brain ultrasonograph 637:656 brain ultrasonograph suggestive of widening of the posterior fossa 637:702 This article reports on a Moroccan infant who presented at birth with moderate floppiness, high serum creatine kinase (CK) levels, and brain ultrasonograph suggestive of widening of the posterior fossa. 23420653 2 40 theme muscular 332:339 arg1 dystrophy 341:349 a limb girdle muscular dystrophy 2I 318:352 a limb girdle muscular dystrophy 2I (LGMD2I) 318:361 Mutations in the FKRP gene cause a spectrum of diseases ranging from a limb girdle muscular dystrophy 2I (LGMD2I), to severe Walker-Warburg or muscle-eye-brain forms and a congenital muscular dystrophy (with or without mental retardation) termed MDC1C. 23420653 2 40 theme muscular 332:339 arg1 LGMD2I 355:360 LGMD2I 355:360 LGMD2I 355:360 Mutations in the FKRP gene cause a spectrum of diseases ranging from a limb girdle muscular dystrophy 2I (LGMD2I), to severe Walker-Warburg or muscle-eye-brain forms and a congenital muscular dystrophy (with or without mental retardation) termed MDC1C. 23420653 3 41 theme brain 637:641 arg1 ultrasonograph 643:656 brain ultrasonograph 637:656 brain ultrasonograph suggestive of widening of the posterior fossa 637:702 This article reports on a Moroccan infant who presented at birth with moderate floppiness, high serum creatine kinase (CK) levels, and brain ultrasonograph suggestive of widening of the posterior fossa. 23420653 3 42 theme serum 598:602 arg1 CK 621:622 CK 621:622 CK 621:622 This article reports on a Moroccan infant who presented at birth with moderate floppiness, high serum creatine kinase (CK) levels, and brain ultrasonograph suggestive of widening of the posterior fossa. 23420653 3 42 theme serum 598:602 arg1 kinase 613:618 serum creatine kinase 598:618 high serum creatine kinase (CK) levels 593:630 This article reports on a Moroccan infant who presented at birth with moderate floppiness, high serum creatine kinase (CK) levels, and brain ultrasonograph suggestive of widening of the posterior fossa. 23420653 1 43 theme Fukutin-related 125:139 arg1 glycosyltransferase 170:188 a putative glycosyltransferase 159:188 a putative glycosyltransferase that mediate O-linked glycosylation of the α-dystroglycan 159:246 Fukutin-related protein (FKRP) is a putative glycosyltransferase that mediate O-linked glycosylation of the α-dystroglycan. 23420653 1 43 theme Fukutin-related 125:139 arg1 FKRP 150:153 FKRP 150:153 FKRP 150:153 Fukutin-related protein (FKRP) is a putative glycosyltransferase that mediate O-linked glycosylation of the α-dystroglycan. 23420653 1 43 theme Fukutin-related 125:139 arg1 protein 141:147 Fukutin-related protein 125:147 Fukutin-related protein (FKRP) 125:154 Fukutin-related protein (FKRP) is a putative glycosyltransferase that mediate O-linked glycosylation of the α-dystroglycan. 23420653 2 44 theme FKRP 266:269 arg1 gene 271:274 the FKRP gene 262:274 the FKRP gene 262:274 Mutations in the FKRP gene cause a spectrum of diseases ranging from a limb girdle muscular dystrophy 2I (LGMD2I), to severe Walker-Warburg or muscle-eye-brain forms and a congenital muscular dystrophy (with or without mental retardation) termed MDC1C. 23420653 2 45 theme limb 320:323 arg1 dystrophy 341:349 a limb girdle muscular dystrophy 2I 318:352 a limb girdle muscular dystrophy 2I (LGMD2I) 318:361 Mutations in the FKRP gene cause a spectrum of diseases ranging from a limb girdle muscular dystrophy 2I (LGMD2I), to severe Walker-Warburg or muscle-eye-brain forms and a congenital muscular dystrophy (with or without mental retardation) termed MDC1C. 23420653 2 45 theme limb 320:323 arg1 LGMD2I 355:360 LGMD2I 355:360 LGMD2I 355:360 Mutations in the FKRP gene cause a spectrum of diseases ranging from a limb girdle muscular dystrophy 2I (LGMD2I), to severe Walker-Warburg or muscle-eye-brain forms and a congenital muscular dystrophy (with or without mental retardation) termed MDC1C. 23420653 1 46 theme α-dystroglycan 233:246 arg1 glycosylation 212:224 O-linked glycosylation 203:224 O-linked glycosylation of the α-dystroglycan 203:246 Fukutin-related protein (FKRP) is a putative glycosyltransferase that mediate O-linked glycosylation of the α-dystroglycan. 23420653 4 47 theme α-distroglycan 782:795 arg1 absence 771:777 complete absence 762:777 complete absence of α-distroglycan 762:795 Muscle biopsy displayed moderate dystrophic pattern with complete absence of α-distroglycan and genetic studies identified a homozygous missense variant in FKRP. 23420653 5 48 from Mutations 867:875 arg1 FKRP 880:883 FKRP 880:883 FKRP 880:883 Mutations in FKRP should be looked for in forms of neonatal-onset hyperCKaemia with floppiness and small cerebellum. 23420653 2 49 theme severe 367:372 arg1 forms 409:413 severe Walker-Warburg or muscle-eye-brain forms 367:413 severe Walker-Warburg or muscle-eye-brain forms 367:413 Mutations in the FKRP gene cause a spectrum of diseases ranging from a limb girdle muscular dystrophy 2I (LGMD2I), to severe Walker-Warburg or muscle-eye-brain forms and a congenital muscular dystrophy (with or without mental retardation) termed MDC1C. 23420653 3 50 theme high 593:596 arg1 levels 625:630 high serum creatine kinase (CK) levels 593:630 high serum creatine kinase (CK) levels 593:630 This article reports on a Moroccan infant who presented at birth with moderate floppiness, high serum creatine kinase (CK) levels, and brain ultrasonograph suggestive of widening of the posterior fossa. 23420653 5 51 with hyperCKaemia 933:944 arg1 floppiness 951:960 floppiness 951:960 floppiness 951:960 Mutations in FKRP should be looked for in forms of neonatal-onset hyperCKaemia with floppiness and small cerebellum. 23420653 5 51 with hyperCKaemia 933:944 arg1 cerebellum 972:981 small cerebellum 966:981 small cerebellum 966:981 Mutations in FKRP should be looked for in forms of neonatal-onset hyperCKaemia with floppiness and small cerebellum. 28150883 3 0 theme biochemical 550:560 arg1 techniques 562:571 the classical biochemical techniques 536:571 the classical biochemical techniques 536:571 Numerous methods have been developed for the analysis of protein O-GlcNAcylation, but instead of discussing the classical biochemical techniques, this unit covers O-GlcNAc characterization by combining several enrichment methods and mass spectrometry detection techniques [including collision-induced dissociation (CID), higher energy collision dissociation (HCD), and electron transfer dissociation (ETD) mass spectrometry]. 28150883 2 1 dep initiation 312:321 arg1 the 308:310 the 308:310 the 308:310 Aberrant O-GlcNAcylation underlies the initiation and progression of multiple chronic diseases including diabetes, cancer, and neurodegenerative diseases. 28150883 3 2 theme collision-induced 711:727 arg1 CID 743:745 CID 743:745 CID 743:745 Numerous methods have been developed for the analysis of protein O-GlcNAcylation, but instead of discussing the classical biochemical techniques, this unit covers O-GlcNAc characterization by combining several enrichment methods and mass spectrometry detection techniques [including collision-induced dissociation (CID), higher energy collision dissociation (HCD), and electron transfer dissociation (ETD) mass spectrometry]. 28150883 3 2 theme collision-induced 711:727 arg1 dissociation 729:740 collision-induced dissociation 711:740 collision-induced dissociation (CID) 711:746 Numerous methods have been developed for the analysis of protein O-GlcNAcylation, but instead of discussing the classical biochemical techniques, this unit covers O-GlcNAc characterization by combining several enrichment methods and mass spectrometry detection techniques [including collision-induced dissociation (CID), higher energy collision dissociation (HCD), and electron transfer dissociation (ETD) mass spectrometry]. 28150883 1 3 theme O-linked 58:65 arg1 modification 152:163 a post-translational modification 131:163 a post-translational modification of serine/threonine residues of proteins 131:204 O-linked β-D-N-acetyl glucosamine (O-GlcNAc) addition (O-GlcNAcylation), a post-translational modification of serine/threonine residues of proteins, is involved in diverse cellular metabolic and signaling pathways. 28150883 1 3 theme O-linked 58:65 arg1 O-GlcNAcylation 113:127 O-GlcNAcylation 113:127 O-GlcNAcylation 113:127 O-linked β-D-N-acetyl glucosamine (O-GlcNAc) addition (O-GlcNAcylation), a post-translational modification of serine/threonine residues of proteins, is involved in diverse cellular metabolic and signaling pathways. 28150883 1 3 theme O-linked 58:65 arg1 addition 103:110 O-linked β-D-N-acetyl glucosamine (O-GlcNAc) addition 58:110 O-linked β-D-N-acetyl glucosamine (O-GlcNAc) addition (O-GlcNAcylation) 58:128 O-linked β-D-N-acetyl glucosamine (O-GlcNAc) addition (O-GlcNAcylation), a post-translational modification of serine/threonine residues of proteins, is involved in diverse cellular metabolic and signaling pathways. 28150883 3 4 theme several 630:636 arg1 methods 649:655 several enrichment methods 630:655 several enrichment methods 630:655 Numerous methods have been developed for the analysis of protein O-GlcNAcylation, but instead of discussing the classical biochemical techniques, this unit covers O-GlcNAc characterization by combining several enrichment methods and mass spectrometry detection techniques [including collision-induced dissociation (CID), higher energy collision dissociation (HCD), and electron transfer dissociation (ETD) mass spectrometry]. 28150883 3 5 theme electron 797:804 arg1 ETD 829:831 ETD 829:831 ETD 829:831 Numerous methods have been developed for the analysis of protein O-GlcNAcylation, but instead of discussing the classical biochemical techniques, this unit covers O-GlcNAc characterization by combining several enrichment methods and mass spectrometry detection techniques [including collision-induced dissociation (CID), higher energy collision dissociation (HCD), and electron transfer dissociation (ETD) mass spectrometry]. 28150883 3 5 theme electron 797:804 arg1 dissociation 815:826 electron transfer dissociation 797:826 electron transfer dissociation (ETD) 797:832 Numerous methods have been developed for the analysis of protein O-GlcNAcylation, but instead of discussing the classical biochemical techniques, this unit covers O-GlcNAc characterization by combining several enrichment methods and mass spectrometry detection techniques [including collision-induced dissociation (CID), higher energy collision dissociation (HCD), and electron transfer dissociation (ETD) mass spectrometry]. 28150883 1 6 theme β-D-N-acetyl 67:78 arg1 glucosamine 80:90 β-D-N-acetyl glucosamine 67:90 O-linked β-D-N-acetyl glucosamine (O-GlcNAc) addition (O-GlcNAcylation) 58:128 O-linked β-D-N-acetyl glucosamine (O-GlcNAc) addition (O-GlcNAcylation), a post-translational modification of serine/threonine residues of proteins, is involved in diverse cellular metabolic and signaling pathways. 28150883 1 6 theme β-D-N-acetyl 67:78 arg1 O-GlcNAc 93:100 O-GlcNAc 93:100 O-GlcNAc 93:100 O-linked β-D-N-acetyl glucosamine (O-GlcNAc) addition (O-GlcNAcylation), a post-translational modification of serine/threonine residues of proteins, is involved in diverse cellular metabolic and signaling pathways. 28150883 1 7 link O-linked 58:65 arg1 modification 152:163 a post-translational modification 131:163 a post-translational modification of serine/threonine residues of proteins 131:204 O-linked β-D-N-acetyl glucosamine (O-GlcNAc) addition (O-GlcNAcylation), a post-translational modification of serine/threonine residues of proteins, is involved in diverse cellular metabolic and signaling pathways. 28150883 1 7 link O-linked 58:65 arg1 O-GlcNAcylation 113:127 O-GlcNAcylation 113:127 O-GlcNAcylation 113:127 O-linked β-D-N-acetyl glucosamine (O-GlcNAc) addition (O-GlcNAcylation), a post-translational modification of serine/threonine residues of proteins, is involved in diverse cellular metabolic and signaling pathways. 28150883 1 7 link O-linked 58:65 arg1 addition 103:110 O-linked β-D-N-acetyl glucosamine (O-GlcNAc) addition 58:110 O-linked β-D-N-acetyl glucosamine (O-GlcNAc) addition (O-GlcNAcylation) 58:128 O-linked β-D-N-acetyl glucosamine (O-GlcNAc) addition (O-GlcNAcylation), a post-translational modification of serine/threonine residues of proteins, is involved in diverse cellular metabolic and signaling pathways. 28150883 3 8 theme transfer 806:813 arg1 ETD 829:831 ETD 829:831 ETD 829:831 Numerous methods have been developed for the analysis of protein O-GlcNAcylation, but instead of discussing the classical biochemical techniques, this unit covers O-GlcNAc characterization by combining several enrichment methods and mass spectrometry detection techniques [including collision-induced dissociation (CID), higher energy collision dissociation (HCD), and electron transfer dissociation (ETD) mass spectrometry]. 28150883 3 8 theme transfer 806:813 arg1 dissociation 815:826 electron transfer dissociation 797:826 electron transfer dissociation (ETD) 797:832 Numerous methods have been developed for the analysis of protein O-GlcNAcylation, but instead of discussing the classical biochemical techniques, this unit covers O-GlcNAc characterization by combining several enrichment methods and mass spectrometry detection techniques [including collision-induced dissociation (CID), higher energy collision dissociation (HCD), and electron transfer dissociation (ETD) mass spectrometry]. 28150883 1 9 theme glucosamine 80:90 arg1 modification 152:163 a post-translational modification 131:163 a post-translational modification of serine/threonine residues of proteins 131:204 O-linked β-D-N-acetyl glucosamine (O-GlcNAc) addition (O-GlcNAcylation), a post-translational modification of serine/threonine residues of proteins, is involved in diverse cellular metabolic and signaling pathways. 28150883 1 9 theme glucosamine 80:90 arg1 O-GlcNAcylation 113:127 O-GlcNAcylation 113:127 O-GlcNAcylation 113:127 O-linked β-D-N-acetyl glucosamine (O-GlcNAc) addition (O-GlcNAcylation), a post-translational modification of serine/threonine residues of proteins, is involved in diverse cellular metabolic and signaling pathways. 28150883 1 9 theme glucosamine 80:90 arg1 addition 103:110 O-linked β-D-N-acetyl glucosamine (O-GlcNAc) addition 58:110 O-linked β-D-N-acetyl glucosamine (O-GlcNAc) addition (O-GlcNAcylation) 58:128 O-linked β-D-N-acetyl glucosamine (O-GlcNAc) addition (O-GlcNAcylation), a post-translational modification of serine/threonine residues of proteins, is involved in diverse cellular metabolic and signaling pathways. 28150883 1 10 theme residues 185:192 arg1 modification 152:163 a post-translational modification 131:163 a post-translational modification of serine/threonine residues of proteins 131:204 O-linked β-D-N-acetyl glucosamine (O-GlcNAc) addition (O-GlcNAcylation), a post-translational modification of serine/threonine residues of proteins, is involved in diverse cellular metabolic and signaling pathways. 28150883 1 10 theme residues 185:192 arg1 addition 103:110 O-linked β-D-N-acetyl glucosamine (O-GlcNAc) addition 58:110 O-linked β-D-N-acetyl glucosamine (O-GlcNAc) addition (O-GlcNAcylation) 58:128 O-linked β-D-N-acetyl glucosamine (O-GlcNAc) addition (O-GlcNAcylation), a post-translational modification of serine/threonine residues of proteins, is involved in diverse cellular metabolic and signaling pathways. 28150883 3 11 theme protein 485:491 arg1 O-GlcNAcylation 493:507 protein O-GlcNAcylation 485:507 protein O-GlcNAcylation 485:507 Numerous methods have been developed for the analysis of protein O-GlcNAcylation, but instead of discussing the classical biochemical techniques, this unit covers O-GlcNAc characterization by combining several enrichment methods and mass spectrometry detection techniques [including collision-induced dissociation (CID), higher energy collision dissociation (HCD), and electron transfer dissociation (ETD) mass spectrometry]. 28150883 3 12 theme Numerous 428:435 arg1 methods 437:443 Numerous methods 428:443 Numerous methods 428:443 Numerous methods have been developed for the analysis of protein O-GlcNAcylation, but instead of discussing the classical biochemical techniques, this unit covers O-GlcNAc characterization by combining several enrichment methods and mass spectrometry detection techniques [including collision-induced dissociation (CID), higher energy collision dissociation (HCD), and electron transfer dissociation (ETD) mass spectrometry]. 28150883 2 13 theme chronic 351:357 arg1 diabetes 378:385 diabetes 378:385 diabetes 378:385 Aberrant O-GlcNAcylation underlies the initiation and progression of multiple chronic diseases including diabetes, cancer, and neurodegenerative diseases. 28150883 2 13 theme chronic 351:357 arg1 diseases 359:366 multiple chronic diseases 342:366 multiple chronic diseases including diabetes, cancer, and neurodegenerative diseases 342:425 Aberrant O-GlcNAcylation underlies the initiation and progression of multiple chronic diseases including diabetes, cancer, and neurodegenerative diseases. 28150883 2 13 theme chronic 351:357 arg1 diseases 418:425 neurodegenerative diseases 400:425 neurodegenerative diseases 400:425 Aberrant O-GlcNAcylation underlies the initiation and progression of multiple chronic diseases including diabetes, cancer, and neurodegenerative diseases. 28150883 2 13 theme chronic 351:357 arg1 cancer 388:393 cancer 388:393 cancer 388:393 Aberrant O-GlcNAcylation underlies the initiation and progression of multiple chronic diseases including diabetes, cancer, and neurodegenerative diseases. 28150883 1 14 theme proteins 197:204 arg1 proteins 197:204 proteins 197:204 proteins 197:204 O-linked β-D-N-acetyl glucosamine (O-GlcNAc) addition (O-GlcNAcylation), a post-translational modification of serine/threonine residues of proteins, is involved in diverse cellular metabolic and signaling pathways. 28150883 1 14 theme proteins 197:204 arg1 residues 185:192 serine/threonine residues 168:192 serine/threonine residues of proteins 168:204 O-linked β-D-N-acetyl glucosamine (O-GlcNAc) addition (O-GlcNAcylation), a post-translational modification of serine/threonine residues of proteins, is involved in diverse cellular metabolic and signaling pathways. 28150883 2 15 theme multiple 342:349 arg1 diabetes 378:385 diabetes 378:385 diabetes 378:385 Aberrant O-GlcNAcylation underlies the initiation and progression of multiple chronic diseases including diabetes, cancer, and neurodegenerative diseases. 28150883 2 15 theme multiple 342:349 arg1 diseases 359:366 multiple chronic diseases 342:366 multiple chronic diseases including diabetes, cancer, and neurodegenerative diseases 342:425 Aberrant O-GlcNAcylation underlies the initiation and progression of multiple chronic diseases including diabetes, cancer, and neurodegenerative diseases. 28150883 2 15 theme multiple 342:349 arg1 diseases 418:425 neurodegenerative diseases 400:425 neurodegenerative diseases 400:425 Aberrant O-GlcNAcylation underlies the initiation and progression of multiple chronic diseases including diabetes, cancer, and neurodegenerative diseases. 28150883 2 15 theme multiple 342:349 arg1 cancer 388:393 cancer 388:393 cancer 388:393 Aberrant O-GlcNAcylation underlies the initiation and progression of multiple chronic diseases including diabetes, cancer, and neurodegenerative diseases. 28150883 0 16 theme O-GlcNAcylation 20:34 arg1 Analysis 0:7 Analysis 0:7 Analysis of Protein O-GlcNAcylation by Mass Spectrometry. 0:56 Analysis of Protein O-GlcNAcylation by Mass Spectrometry. 28150883 4 17 theme John 864:867 arg1 Sons 877:880 John Wiley & Sons 864:880 John Wiley & Sons 864:880 © 2017 by John Wiley & Sons, Inc. 28150883 4 18 theme & 875:875 arg1 Sons 877:880 John Wiley & Sons 864:880 John Wiley & Sons 864:880 © 2017 by John Wiley & Sons, Inc. 28150883 0 19 theme Protein 12:18 arg1 O-GlcNAcylation 20:34 Protein O-GlcNAcylation 12:34 Protein O-GlcNAcylation 12:34 Analysis of Protein O-GlcNAcylation by Mass Spectrometry. 28150883 1 20 theme serine/threonine 168:183 arg1 proteins 197:204 proteins 197:204 proteins 197:204 O-linked β-D-N-acetyl glucosamine (O-GlcNAc) addition (O-GlcNAcylation), a post-translational modification of serine/threonine residues of proteins, is involved in diverse cellular metabolic and signaling pathways. 28150883 1 20 theme serine/threonine 168:183 arg1 residues 185:192 serine/threonine residues 168:192 serine/threonine residues of proteins 168:204 O-linked β-D-N-acetyl glucosamine (O-GlcNAc) addition (O-GlcNAcylation), a post-translational modification of serine/threonine residues of proteins, is involved in diverse cellular metabolic and signaling pathways. 28150883 1 21 theme post-translational 133:150 arg1 modification 152:163 a post-translational modification 131:163 a post-translational modification of serine/threonine residues of proteins 131:204 O-linked β-D-N-acetyl glucosamine (O-GlcNAc) addition (O-GlcNAcylation), a post-translational modification of serine/threonine residues of proteins, is involved in diverse cellular metabolic and signaling pathways. 28150883 1 21 theme post-translational 133:150 arg1 addition 103:110 O-linked β-D-N-acetyl glucosamine (O-GlcNAc) addition 58:110 O-linked β-D-N-acetyl glucosamine (O-GlcNAc) addition (O-GlcNAcylation) 58:128 O-linked β-D-N-acetyl glucosamine (O-GlcNAc) addition (O-GlcNAcylation), a post-translational modification of serine/threonine residues of proteins, is involved in diverse cellular metabolic and signaling pathways. 28150883 0 22 theme Mass 39:42 arg1 Spectrometry 44:55 Mass Spectrometry 39:55 Mass Spectrometry 39:55 Analysis of Protein O-GlcNAcylation by Mass Spectrometry. 28150883 3 23 theme mass 661:664 arg1 techniques 689:698 mass spectrometry detection techniques 661:698 mass spectrometry detection techniques 661:698 Numerous methods have been developed for the analysis of protein O-GlcNAcylation, but instead of discussing the classical biochemical techniques, this unit covers O-GlcNAc characterization by combining several enrichment methods and mass spectrometry detection techniques [including collision-induced dissociation (CID), higher energy collision dissociation (HCD), and electron transfer dissociation (ETD) mass spectrometry]. 28150883 3 24 theme O-GlcNAcylation 493:507 arg1 analysis 473:480 the analysis 469:480 the analysis of protein O-GlcNAcylation 469:507 Numerous methods have been developed for the analysis of protein O-GlcNAcylation, but instead of discussing the classical biochemical techniques, this unit covers O-GlcNAc characterization by combining several enrichment methods and mass spectrometry detection techniques [including collision-induced dissociation (CID), higher energy collision dissociation (HCD), and electron transfer dissociation (ETD) mass spectrometry]. 28150883 3 25 theme spectrometry 666:677 arg1 techniques 689:698 mass spectrometry detection techniques 661:698 mass spectrometry detection techniques 661:698 Numerous methods have been developed for the analysis of protein O-GlcNAcylation, but instead of discussing the classical biochemical techniques, this unit covers O-GlcNAc characterization by combining several enrichment methods and mass spectrometry detection techniques [including collision-induced dissociation (CID), higher energy collision dissociation (HCD), and electron transfer dissociation (ETD) mass spectrometry]. 28150883 3 26 theme mass 834:837 arg1 spectrometry 839:850 mass spectrometry 834:850 mass spectrometry 834:850 Numerous methods have been developed for the analysis of protein O-GlcNAcylation, but instead of discussing the classical biochemical techniques, this unit covers O-GlcNAc characterization by combining several enrichment methods and mass spectrometry detection techniques [including collision-induced dissociation (CID), higher energy collision dissociation (HCD), and electron transfer dissociation (ETD) mass spectrometry]. 28150883 3 27 theme energy 756:761 arg1 HCD 787:789 HCD 787:789 HCD 787:789 Numerous methods have been developed for the analysis of protein O-GlcNAcylation, but instead of discussing the classical biochemical techniques, this unit covers O-GlcNAc characterization by combining several enrichment methods and mass spectrometry detection techniques [including collision-induced dissociation (CID), higher energy collision dissociation (HCD), and electron transfer dissociation (ETD) mass spectrometry]. 28150883 3 27 theme energy 756:761 arg1 dissociation 773:784 higher energy collision dissociation 749:784 higher energy collision dissociation (HCD) 749:790 Numerous methods have been developed for the analysis of protein O-GlcNAcylation, but instead of discussing the classical biochemical techniques, this unit covers O-GlcNAc characterization by combining several enrichment methods and mass spectrometry detection techniques [including collision-induced dissociation (CID), higher energy collision dissociation (HCD), and electron transfer dissociation (ETD) mass spectrometry]. 28150883 3 28 theme classical 540:548 arg1 techniques 562:571 the classical biochemical techniques 536:571 the classical biochemical techniques 536:571 Numerous methods have been developed for the analysis of protein O-GlcNAcylation, but instead of discussing the classical biochemical techniques, this unit covers O-GlcNAc characterization by combining several enrichment methods and mass spectrometry detection techniques [including collision-induced dissociation (CID), higher energy collision dissociation (HCD), and electron transfer dissociation (ETD) mass spectrometry]. 28150883 3 29 theme collision 763:771 arg1 HCD 787:789 HCD 787:789 HCD 787:789 Numerous methods have been developed for the analysis of protein O-GlcNAcylation, but instead of discussing the classical biochemical techniques, this unit covers O-GlcNAc characterization by combining several enrichment methods and mass spectrometry detection techniques [including collision-induced dissociation (CID), higher energy collision dissociation (HCD), and electron transfer dissociation (ETD) mass spectrometry]. 28150883 3 29 theme collision 763:771 arg1 dissociation 773:784 higher energy collision dissociation 749:784 higher energy collision dissociation (HCD) 749:790 Numerous methods have been developed for the analysis of protein O-GlcNAcylation, but instead of discussing the classical biochemical techniques, this unit covers O-GlcNAc characterization by combining several enrichment methods and mass spectrometry detection techniques [including collision-induced dissociation (CID), higher energy collision dissociation (HCD), and electron transfer dissociation (ETD) mass spectrometry]. 28150883 4 30 theme Wiley 869:873 arg1 Sons 877:880 John Wiley & Sons 864:880 John Wiley & Sons 864:880 © 2017 by John Wiley & Sons, Inc. 28150883 3 31 dep dissociation 729:740 arg1 spectrometry 839:850 mass spectrometry 834:850 mass spectrometry 834:850 Numerous methods have been developed for the analysis of protein O-GlcNAcylation, but instead of discussing the classical biochemical techniques, this unit covers O-GlcNAc characterization by combining several enrichment methods and mass spectrometry detection techniques [including collision-induced dissociation (CID), higher energy collision dissociation (HCD), and electron transfer dissociation (ETD) mass spectrometry]. 28150883 2 32 theme Aberrant 273:280 arg1 O-GlcNAcylation 282:296 Aberrant O-GlcNAcylation 273:296 Aberrant O-GlcNAcylation 273:296 Aberrant O-GlcNAcylation underlies the initiation and progression of multiple chronic diseases including diabetes, cancer, and neurodegenerative diseases. 28150883 2 33 theme diseases 359:366 arg1 initiation 312:321 initiation 312:321 initiation 312:321 Aberrant O-GlcNAcylation underlies the initiation and progression of multiple chronic diseases including diabetes, cancer, and neurodegenerative diseases. 28150883 2 33 theme diseases 359:366 arg1 progression 327:337 progression 327:337 progression 327:337 Aberrant O-GlcNAcylation underlies the initiation and progression of multiple chronic diseases including diabetes, cancer, and neurodegenerative diseases. 28150883 3 34 theme higher 749:754 arg1 HCD 787:789 HCD 787:789 HCD 787:789 Numerous methods have been developed for the analysis of protein O-GlcNAcylation, but instead of discussing the classical biochemical techniques, this unit covers O-GlcNAc characterization by combining several enrichment methods and mass spectrometry detection techniques [including collision-induced dissociation (CID), higher energy collision dissociation (HCD), and electron transfer dissociation (ETD) mass spectrometry]. 28150883 3 34 theme higher 749:754 arg1 dissociation 773:784 higher energy collision dissociation 749:784 higher energy collision dissociation (HCD) 749:790 Numerous methods have been developed for the analysis of protein O-GlcNAcylation, but instead of discussing the classical biochemical techniques, this unit covers O-GlcNAc characterization by combining several enrichment methods and mass spectrometry detection techniques [including collision-induced dissociation (CID), higher energy collision dissociation (HCD), and electron transfer dissociation (ETD) mass spectrometry]. 28150883 3 35 theme detection 679:687 arg1 techniques 689:698 mass spectrometry detection techniques 661:698 mass spectrometry detection techniques 661:698 Numerous methods have been developed for the analysis of protein O-GlcNAcylation, but instead of discussing the classical biochemical techniques, this unit covers O-GlcNAc characterization by combining several enrichment methods and mass spectrometry detection techniques [including collision-induced dissociation (CID), higher energy collision dissociation (HCD), and electron transfer dissociation (ETD) mass spectrometry]. 28150883 2 36 theme neurodegenerative 400:416 arg1 diseases 418:425 neurodegenerative diseases 400:425 neurodegenerative diseases 400:425 Aberrant O-GlcNAcylation underlies the initiation and progression of multiple chronic diseases including diabetes, cancer, and neurodegenerative diseases. 28150883 3 37 theme O-GlcNAc 591:598 arg1 characterization 600:615 O-GlcNAc characterization 591:615 O-GlcNAc characterization 591:615 Numerous methods have been developed for the analysis of protein O-GlcNAcylation, but instead of discussing the classical biochemical techniques, this unit covers O-GlcNAc characterization by combining several enrichment methods and mass spectrometry detection techniques [including collision-induced dissociation (CID), higher energy collision dissociation (HCD), and electron transfer dissociation (ETD) mass spectrometry]. 28150883 3 38 theme enrichment 638:647 arg1 methods 649:655 several enrichment methods 630:655 several enrichment methods 630:655 Numerous methods have been developed for the analysis of protein O-GlcNAcylation, but instead of discussing the classical biochemical techniques, this unit covers O-GlcNAc characterization by combining several enrichment methods and mass spectrometry detection techniques [including collision-induced dissociation (CID), higher energy collision dissociation (HCD), and electron transfer dissociation (ETD) mass spectrometry]. 28150883 1 39 theme signaling 253:261 arg1 pathways 263:270 signaling pathways 253:270 signaling pathways 253:270 O-linked β-D-N-acetyl glucosamine (O-GlcNAc) addition (O-GlcNAcylation), a post-translational modification of serine/threonine residues of proteins, is involved in diverse cellular metabolic and signaling pathways. 29125760 3 0 theme catalytic 546:554 arg1 version 574:580 A catalytic, enantioselective version 544:580 version 574:580 A catalytic, enantioselective version of this NCAL process using isothiourea catalysts provided access to bicyclic β-lactone-fused, N-heterocycles in moderate to good yields (up to 80%) with high enantiocontrol (up to >99:1 er). 29125760 2 1 theme Lewis 532:536 arg1 4-pyrrolidinopyridine 486:506 4-pyrrolidinopyridine 486:506 4-pyrrolidinopyridine 486:506 A series of bi- and tricyclic, N-heterocycle-fused, β-lactones were first synthesized in racemic fashion via the NCAL process with excellent diastereoselectivity (>19:1) utilizing 4-pyrrolidinopyridine as an effective achiral Lewis base. 29125760 2 1 theme Lewis 532:536 arg1 base 538:541 an effective achiral Lewis base 511:541 an effective achiral Lewis base 511:541 A series of bi- and tricyclic, N-heterocycle-fused, β-lactones were first synthesized in racemic fashion via the NCAL process with excellent diastereoselectivity (>19:1) utilizing 4-pyrrolidinopyridine as an effective achiral Lewis base. 29125760 2 2 with process 424:430 arg1 >19:1 469:473 >19:1 469:473 >19:1 469:473 A series of bi- and tricyclic, N-heterocycle-fused, β-lactones were first synthesized in racemic fashion via the NCAL process with excellent diastereoselectivity (>19:1) utilizing 4-pyrrolidinopyridine as an effective achiral Lewis base. 29125760 2 2 with process 424:430 arg1 diastereoselectivity 447:466 excellent diastereoselectivity 437:466 excellent diastereoselectivity (>19:1) utilizing 4-pyrrolidinopyridine as an effective achiral Lewis base 437:541 A series of bi- and tricyclic, N-heterocycle-fused, β-lactones were first synthesized in racemic fashion via the NCAL process with excellent diastereoselectivity (>19:1) utilizing 4-pyrrolidinopyridine as an effective achiral Lewis base. 29125760 1 3 theme NCAL 170:173 arg1 process 176:182 the nucleophile-catalyzed (Lewis base) aldol lactonization (NCAL) process 110:182 the nucleophile-catalyzed (Lewis base) aldol lactonization (NCAL) process 110:182 The utility of the nucleophile-catalyzed (Lewis base) aldol lactonization (NCAL) process for the diastereo- and enantioselective synthesis of N-heterocycle-fused-β-lactones from N-linked ketoacids is described. 29125760 2 4 theme β-lactones 358:367 arg1 series 308:313 A series 306:313 A series of bi- and tricyclic, N-heterocycle-fused, β-lactones 306:367 A series of bi- and tricyclic, N-heterocycle-fused, β-lactones were first synthesized in racemic fashion via the NCAL process with excellent diastereoselectivity (>19:1) utilizing 4-pyrrolidinopyridine as an effective achiral Lewis base. 29125760 4 5 theme tricyclic 993:1001 arg1 β-lactone 1003:1011 the diastereomeric tricyclic β-lactone 974:1011 the diastereomeric tricyclic β-lactone 974:1011 An unusual diastereodivergent NCAL process was discovered that leads to two different products; a tricyclic N-heterocycle-fused β-lactone and a bicyclic enamine derived from in situ decarboxylation of the diastereomeric tricyclic β-lactone. 29125760 4 6 theme bicyclic 917:924 arg1 enamine 926:932 a bicyclic enamine 915:932 a bicyclic enamine derived from in situ decarboxylation of the diastereomeric tricyclic β-lactone 915:1011 An unusual diastereodivergent NCAL process was discovered that leads to two different products; a tricyclic N-heterocycle-fused β-lactone and a bicyclic enamine derived from in situ decarboxylation of the diastereomeric tricyclic β-lactone. 29125760 4 6 theme bicyclic 917:924 arg1 products 859:866 two different products 845:866 two different products; a tricyclic N-heterocycle-fused β-lactone and a bicyclic enamine derived from in situ decarboxylation of the diastereomeric tricyclic β-lactone 845:1011 An unusual diastereodivergent NCAL process was discovered that leads to two different products; a tricyclic N-heterocycle-fused β-lactone and a bicyclic enamine derived from in situ decarboxylation of the diastereomeric tricyclic β-lactone. 29125760 2 7 theme bi- 318:320 arg1 series 308:313 A series 306:313 A series of bi- and tricyclic, N-heterocycle-fused, β-lactones 306:367 A series of bi- and tricyclic, N-heterocycle-fused, β-lactones were first synthesized in racemic fashion via the NCAL process with excellent diastereoselectivity (>19:1) utilizing 4-pyrrolidinopyridine as an effective achiral Lewis base. 29125760 3 8 theme isothiourea 609:619 arg1 catalysts 621:629 isothiourea catalysts 609:629 isothiourea catalysts 609:629 A catalytic, enantioselective version of this NCAL process using isothiourea catalysts provided access to bicyclic β-lactone-fused, N-heterocycles in moderate to good yields (up to 80%) with high enantiocontrol (up to >99:1 er). 29125760 3 9 dep 80 725:726 arg1 to 722:723 to 722:723 to 722:723 A catalytic, enantioselective version of this NCAL process using isothiourea catalysts provided access to bicyclic β-lactone-fused, N-heterocycles in moderate to good yields (up to 80%) with high enantiocontrol (up to >99:1 er). 29125760 4 10 theme diastereomeric 978:991 arg1 β-lactone 1003:1011 the diastereomeric tricyclic β-lactone 974:1011 the diastereomeric tricyclic β-lactone 974:1011 An unusual diastereodivergent NCAL process was discovered that leads to two different products; a tricyclic N-heterocycle-fused β-lactone and a bicyclic enamine derived from in situ decarboxylation of the diastereomeric tricyclic β-lactone. 29125760 4 11 theme unusual 776:782 arg1 process 808:814 An unusual diastereodivergent NCAL process 773:814 An unusual diastereodivergent NCAL process 773:814 An unusual diastereodivergent NCAL process was discovered that leads to two different products; a tricyclic N-heterocycle-fused β-lactone and a bicyclic enamine derived from in situ decarboxylation of the diastereomeric tricyclic β-lactone. 29125760 3 12 theme process 595:601 arg1 version 574:580 A catalytic, enantioselective version 544:580 version 574:580 A catalytic, enantioselective version of this NCAL process using isothiourea catalysts provided access to bicyclic β-lactone-fused, N-heterocycles in moderate to good yields (up to 80%) with high enantiocontrol (up to >99:1 er). 29125760 4 13 theme β-lactone 1003:1011 arg1 decarboxylation 955:969 in situ decarboxylation 947:969 in situ decarboxylation of the diastereomeric tricyclic β-lactone 947:1011 An unusual diastereodivergent NCAL process was discovered that leads to two different products; a tricyclic N-heterocycle-fused β-lactone and a bicyclic enamine derived from in situ decarboxylation of the diastereomeric tricyclic β-lactone. 29125760 2 14 theme achiral 524:530 arg1 4-pyrrolidinopyridine 486:506 4-pyrrolidinopyridine 486:506 4-pyrrolidinopyridine 486:506 A series of bi- and tricyclic, N-heterocycle-fused, β-lactones were first synthesized in racemic fashion via the NCAL process with excellent diastereoselectivity (>19:1) utilizing 4-pyrrolidinopyridine as an effective achiral Lewis base. 29125760 2 14 theme achiral 524:530 arg1 base 538:541 an effective achiral Lewis base 511:541 an effective achiral Lewis base 511:541 A series of bi- and tricyclic, N-heterocycle-fused, β-lactones were first synthesized in racemic fashion via the NCAL process with excellent diastereoselectivity (>19:1) utilizing 4-pyrrolidinopyridine as an effective achiral Lewis base. 29125760 4 15 theme NCAL 803:806 arg1 process 808:814 An unusual diastereodivergent NCAL process 773:814 An unusual diastereodivergent NCAL process 773:814 An unusual diastereodivergent NCAL process was discovered that leads to two different products; a tricyclic N-heterocycle-fused β-lactone and a bicyclic enamine derived from in situ decarboxylation of the diastereomeric tricyclic β-lactone. 29125760 2 16 theme NCAL 419:422 arg1 process 424:430 the NCAL process 415:430 the NCAL process with excellent diastereoselectivity (>19:1) utilizing 4-pyrrolidinopyridine as an effective achiral Lewis base 415:541 A series of bi- and tricyclic, N-heterocycle-fused, β-lactones were first synthesized in racemic fashion via the NCAL process with excellent diastereoselectivity (>19:1) utilizing 4-pyrrolidinopyridine as an effective achiral Lewis base. 29125760 4 17 theme N-heterocycle-fused 881:899 arg1 β-lactone 901:909 a tricyclic N-heterocycle-fused β-lactone 869:909 a tricyclic N-heterocycle-fused β-lactone 869:909 An unusual diastereodivergent NCAL process was discovered that leads to two different products; a tricyclic N-heterocycle-fused β-lactone and a bicyclic enamine derived from in situ decarboxylation of the diastereomeric tricyclic β-lactone. 29125760 4 17 theme N-heterocycle-fused 881:899 arg1 products 859:866 two different products 845:866 two different products; a tricyclic N-heterocycle-fused β-lactone and a bicyclic enamine derived from in situ decarboxylation of the diastereomeric tricyclic β-lactone 845:1011 An unusual diastereodivergent NCAL process was discovered that leads to two different products; a tricyclic N-heterocycle-fused β-lactone and a bicyclic enamine derived from in situ decarboxylation of the diastereomeric tricyclic β-lactone. 29125760 1 18 link N-linked 273:280 arg1 ketoacids 282:290 N-linked ketoacids 273:290 N-linked ketoacids 273:290 The utility of the nucleophile-catalyzed (Lewis base) aldol lactonization (NCAL) process for the diastereo- and enantioselective synthesis of N-heterocycle-fused-β-lactones from N-linked ketoacids is described. 29125760 0 19 theme Diastereo- 0:9 arg1 Synthesis 32:40 Diastereo- and Enantioselective Synthesis 0:40 Diastereo- and Enantioselective Synthesis of Bi- and Tricyclic N-Heterocycle-Fused β-Lactones 0:92 Diastereo- and Enantioselective Synthesis of Bi- and Tricyclic N-Heterocycle-Fused β-Lactones. 29125760 4 20 theme tricyclic 871:879 arg1 β-lactone 901:909 a tricyclic N-heterocycle-fused β-lactone 869:909 a tricyclic N-heterocycle-fused β-lactone 869:909 An unusual diastereodivergent NCAL process was discovered that leads to two different products; a tricyclic N-heterocycle-fused β-lactone and a bicyclic enamine derived from in situ decarboxylation of the diastereomeric tricyclic β-lactone. 29125760 4 20 theme tricyclic 871:879 arg1 products 859:866 two different products 845:866 two different products; a tricyclic N-heterocycle-fused β-lactone and a bicyclic enamine derived from in situ decarboxylation of the diastereomeric tricyclic β-lactone 845:1011 An unusual diastereodivergent NCAL process was discovered that leads to two different products; a tricyclic N-heterocycle-fused β-lactone and a bicyclic enamine derived from in situ decarboxylation of the diastereomeric tricyclic β-lactone. 29125760 4 21 theme diastereodivergent 784:801 arg1 process 808:814 An unusual diastereodivergent NCAL process 773:814 An unusual diastereodivergent NCAL process 773:814 An unusual diastereodivergent NCAL process was discovered that leads to two different products; a tricyclic N-heterocycle-fused β-lactone and a bicyclic enamine derived from in situ decarboxylation of the diastereomeric tricyclic β-lactone. 29125760 2 22 theme tricyclic 326:334 arg1 β-lactones 358:367 tricyclic, N-heterocycle-fused, β-lactones 326:367 tricyclic, N-heterocycle-fused, β-lactones 326:367 A series of bi- and tricyclic, N-heterocycle-fused, β-lactones were first synthesized in racemic fashion via the NCAL process with excellent diastereoselectivity (>19:1) utilizing 4-pyrrolidinopyridine as an effective achiral Lewis base. 29125760 4 23 attach derived 934:940 arg2 products 859:866 two different products 845:866 two different products; a tricyclic N-heterocycle-fused β-lactone and a bicyclic enamine derived from in situ decarboxylation of the diastereomeric tricyclic β-lactone 845:1011 An unusual diastereodivergent NCAL process was discovered that leads to two different products; a tricyclic N-heterocycle-fused β-lactone and a bicyclic enamine derived from in situ decarboxylation of the diastereomeric tricyclic β-lactone. 29125760 4 23 attach derived 934:940 arg2 enamine 926:932 a bicyclic enamine 915:932 a bicyclic enamine derived from in situ decarboxylation of the diastereomeric tricyclic β-lactone 915:1011 An unusual diastereodivergent NCAL process was discovered that leads to two different products; a tricyclic N-heterocycle-fused β-lactone and a bicyclic enamine derived from in situ decarboxylation of the diastereomeric tricyclic β-lactone. 29125760 4 23 attach derived 934:940 arg1 decarboxylation 955:969 in situ decarboxylation 947:969 in situ decarboxylation of the diastereomeric tricyclic β-lactone 947:1011 An unusual diastereodivergent NCAL process was discovered that leads to two different products; a tricyclic N-heterocycle-fused β-lactone and a bicyclic enamine derived from in situ decarboxylation of the diastereomeric tricyclic β-lactone. 29125760 1 24 theme diastereo- 192:201 arg1 synthesis 224:232 the diastereo- and enantioselective synthesis 188:232 the diastereo- and enantioselective synthesis of N-heterocycle-fused-β-lactones from N-linked ketoacids 188:290 The utility of the nucleophile-catalyzed (Lewis base) aldol lactonization (NCAL) process for the diastereo- and enantioselective synthesis of N-heterocycle-fused-β-lactones from N-linked ketoacids is described. 29125760 0 25 theme Enantioselective 15:30 arg1 Synthesis 32:40 Diastereo- and Enantioselective Synthesis 0:40 Diastereo- and Enantioselective Synthesis of Bi- and Tricyclic N-Heterocycle-Fused β-Lactones 0:92 Diastereo- and Enantioselective Synthesis of Bi- and Tricyclic N-Heterocycle-Fused β-Lactones. 29125760 1 26 theme nucleophile-catalyzed 114:134 arg1 process 176:182 the nucleophile-catalyzed (Lewis base) aldol lactonization (NCAL) process 110:182 the nucleophile-catalyzed (Lewis base) aldol lactonization (NCAL) process 110:182 The utility of the nucleophile-catalyzed (Lewis base) aldol lactonization (NCAL) process for the diastereo- and enantioselective synthesis of N-heterocycle-fused-β-lactones from N-linked ketoacids is described. 29125760 3 27 theme enantioselective 557:572 arg1 version 574:580 A catalytic, enantioselective version 544:580 version 574:580 A catalytic, enantioselective version of this NCAL process using isothiourea catalysts provided access to bicyclic β-lactone-fused, N-heterocycles in moderate to good yields (up to 80%) with high enantiocontrol (up to >99:1 er). 29125760 0 28 theme Bi- 45:47 arg1 Synthesis 32:40 Diastereo- and Enantioselective Synthesis 0:40 Diastereo- and Enantioselective Synthesis of Bi- and Tricyclic N-Heterocycle-Fused β-Lactones 0:92 Diastereo- and Enantioselective Synthesis of Bi- and Tricyclic N-Heterocycle-Fused β-Lactones. 29125760 1 29 from ketoacids 282:290 arg1 N-heterocycle-fused-β-lactones 237:266 N-heterocycle-fused-β-lactones 237:266 N-heterocycle-fused-β-lactones from N-linked ketoacids 237:290 The utility of the nucleophile-catalyzed (Lewis base) aldol lactonization (NCAL) process for the diastereo- and enantioselective synthesis of N-heterocycle-fused-β-lactones from N-linked ketoacids is described. 29125760 1 29 from ketoacids 282:290 arg1 synthesis 224:232 the diastereo- and enantioselective synthesis 188:232 the diastereo- and enantioselective synthesis of N-heterocycle-fused-β-lactones from N-linked ketoacids 188:290 The utility of the nucleophile-catalyzed (Lewis base) aldol lactonization (NCAL) process for the diastereo- and enantioselective synthesis of N-heterocycle-fused-β-lactones from N-linked ketoacids is described. 29125760 2 30 theme excellent 437:445 arg1 >19:1 469:473 >19:1 469:473 >19:1 469:473 A series of bi- and tricyclic, N-heterocycle-fused, β-lactones were first synthesized in racemic fashion via the NCAL process with excellent diastereoselectivity (>19:1) utilizing 4-pyrrolidinopyridine as an effective achiral Lewis base. 29125760 2 30 theme excellent 437:445 arg1 diastereoselectivity 447:466 excellent diastereoselectivity 437:466 excellent diastereoselectivity (>19:1) utilizing 4-pyrrolidinopyridine as an effective achiral Lewis base 437:541 A series of bi- and tricyclic, N-heterocycle-fused, β-lactones were first synthesized in racemic fashion via the NCAL process with excellent diastereoselectivity (>19:1) utilizing 4-pyrrolidinopyridine as an effective achiral Lewis base. 29125760 3 31 theme bicyclic 650:657 arg1 N-heterocycles 676:689 bicyclic β-lactone-fused, N-heterocycles 650:689 N-heterocycles 676:689 A catalytic, enantioselective version of this NCAL process using isothiourea catalysts provided access to bicyclic β-lactone-fused, N-heterocycles in moderate to good yields (up to 80%) with high enantiocontrol (up to >99:1 er). 29125760 1 32 theme enantioselective 207:222 arg1 synthesis 224:232 the diastereo- and enantioselective synthesis 188:232 the diastereo- and enantioselective synthesis of N-heterocycle-fused-β-lactones from N-linked ketoacids 188:290 The utility of the nucleophile-catalyzed (Lewis base) aldol lactonization (NCAL) process for the diastereo- and enantioselective synthesis of N-heterocycle-fused-β-lactones from N-linked ketoacids is described. 29125760 2 33 theme effective 514:522 arg1 4-pyrrolidinopyridine 486:506 4-pyrrolidinopyridine 486:506 4-pyrrolidinopyridine 486:506 A series of bi- and tricyclic, N-heterocycle-fused, β-lactones were first synthesized in racemic fashion via the NCAL process with excellent diastereoselectivity (>19:1) utilizing 4-pyrrolidinopyridine as an effective achiral Lewis base. 29125760 2 33 theme effective 514:522 arg1 base 538:541 an effective achiral Lewis base 511:541 an effective achiral Lewis base 511:541 A series of bi- and tricyclic, N-heterocycle-fused, β-lactones were first synthesized in racemic fashion via the NCAL process with excellent diastereoselectivity (>19:1) utilizing 4-pyrrolidinopyridine as an effective achiral Lewis base. 29125760 3 34 theme β-lactone-fused 659:673 arg1 N-heterocycles 676:689 bicyclic β-lactone-fused, N-heterocycles 650:689 N-heterocycles 676:689 A catalytic, enantioselective version of this NCAL process using isothiourea catalysts provided access to bicyclic β-lactone-fused, N-heterocycles in moderate to good yields (up to 80%) with high enantiocontrol (up to >99:1 er). 29125760 0 35 theme Tricyclic 53:61 arg1 β-Lactones 83:92 Tricyclic N-Heterocycle-Fused β-Lactones 53:92 Tricyclic N-Heterocycle-Fused β-Lactones 53:92 Diastereo- and Enantioselective Synthesis of Bi- and Tricyclic N-Heterocycle-Fused β-Lactones. 29125760 3 36 theme good 706:709 arg1 yields 711:716 good yields 706:716 good yields (up to 80%) 706:728 A catalytic, enantioselective version of this NCAL process using isothiourea catalysts provided access to bicyclic β-lactone-fused, N-heterocycles in moderate to good yields (up to 80%) with high enantiocontrol (up to >99:1 er). 29125760 3 36 theme good 706:709 arg1 % 727:727 up to 80% 719:727 up to 80% 719:727 A catalytic, enantioselective version of this NCAL process using isothiourea catalysts provided access to bicyclic β-lactone-fused, N-heterocycles in moderate to good yields (up to 80%) with high enantiocontrol (up to >99:1 er). 29125760 1 37 from synthesis 224:232 arg1 ketoacids 282:290 N-linked ketoacids 273:290 N-linked ketoacids 273:290 The utility of the nucleophile-catalyzed (Lewis base) aldol lactonization (NCAL) process for the diastereo- and enantioselective synthesis of N-heterocycle-fused-β-lactones from N-linked ketoacids is described. 29125760 2 38 dep tricyclic 326:334 arg1 N-heterocycle-fused 337:355 N-heterocycle-fused 337:355 N-heterocycle-fused 337:355 A series of bi- and tricyclic, N-heterocycle-fused, β-lactones were first synthesized in racemic fashion via the NCAL process with excellent diastereoselectivity (>19:1) utilizing 4-pyrrolidinopyridine as an effective achiral Lewis base. 29125760 4 39 theme different 849:857 arg1 enamine 926:932 a bicyclic enamine 915:932 a bicyclic enamine derived from in situ decarboxylation of the diastereomeric tricyclic β-lactone 915:1011 An unusual diastereodivergent NCAL process was discovered that leads to two different products; a tricyclic N-heterocycle-fused β-lactone and a bicyclic enamine derived from in situ decarboxylation of the diastereomeric tricyclic β-lactone. 29125760 4 39 theme different 849:857 arg1 β-lactone 901:909 a tricyclic N-heterocycle-fused β-lactone 869:909 a tricyclic N-heterocycle-fused β-lactone 869:909 An unusual diastereodivergent NCAL process was discovered that leads to two different products; a tricyclic N-heterocycle-fused β-lactone and a bicyclic enamine derived from in situ decarboxylation of the diastereomeric tricyclic β-lactone. 29125760 4 39 theme different 849:857 arg1 products 859:866 two different products 845:866 two different products; a tricyclic N-heterocycle-fused β-lactone and a bicyclic enamine derived from in situ decarboxylation of the diastereomeric tricyclic β-lactone 845:1011 An unusual diastereodivergent NCAL process was discovered that leads to two different products; a tricyclic N-heterocycle-fused β-lactone and a bicyclic enamine derived from in situ decarboxylation of the diastereomeric tricyclic β-lactone. 29125760 1 40 theme Lewis 137:141 arg1 process 176:182 the nucleophile-catalyzed (Lewis base) aldol lactonization (NCAL) process 110:182 the nucleophile-catalyzed (Lewis base) aldol lactonization (NCAL) process 110:182 The utility of the nucleophile-catalyzed (Lewis base) aldol lactonization (NCAL) process for the diastereo- and enantioselective synthesis of N-heterocycle-fused-β-lactones from N-linked ketoacids is described. 29125760 3 41 dep >99:1 762:766 arg1 to 759:760 to 759:760 to 759:760 A catalytic, enantioselective version of this NCAL process using isothiourea catalysts provided access to bicyclic β-lactone-fused, N-heterocycles in moderate to good yields (up to 80%) with high enantiocontrol (up to >99:1 er). 29125760 4 42 theme in 947:948 arg1 decarboxylation 955:969 in situ decarboxylation 947:969 in situ decarboxylation of the diastereomeric tricyclic β-lactone 947:1011 An unusual diastereodivergent NCAL process was discovered that leads to two different products; a tricyclic N-heterocycle-fused β-lactone and a bicyclic enamine derived from in situ decarboxylation of the diastereomeric tricyclic β-lactone. 29125760 5 43 theme adducts 1038:1044 arg1 reactivity 1018:1027 The reactivity 1014:1027 The reactivity of these adducts 1014:1044 The reactivity of these adducts was briefly explored. 29125760 1 44 theme base 143:146 arg1 process 176:182 the nucleophile-catalyzed (Lewis base) aldol lactonization (NCAL) process 110:182 the nucleophile-catalyzed (Lewis base) aldol lactonization (NCAL) process 110:182 The utility of the nucleophile-catalyzed (Lewis base) aldol lactonization (NCAL) process for the diastereo- and enantioselective synthesis of N-heterocycle-fused-β-lactones from N-linked ketoacids is described. 29125760 4 45 dep in 947:948 arg1 situ 950:953 situ 950:953 situ 950:953 An unusual diastereodivergent NCAL process was discovered that leads to two different products; a tricyclic N-heterocycle-fused β-lactone and a bicyclic enamine derived from in situ decarboxylation of the diastereomeric tricyclic β-lactone. 29125760 3 46 theme NCAL 590:593 arg1 process 595:601 this NCAL process 585:601 this NCAL process using isothiourea catalysts 585:629 A catalytic, enantioselective version of this NCAL process using isothiourea catalysts provided access to bicyclic β-lactone-fused, N-heterocycles in moderate to good yields (up to 80%) with high enantiocontrol (up to >99:1 er). 29125760 2 47 theme racemic 395:401 arg1 fashion 403:409 racemic fashion 395:409 racemic fashion 395:409 A series of bi- and tricyclic, N-heterocycle-fused, β-lactones were first synthesized in racemic fashion via the NCAL process with excellent diastereoselectivity (>19:1) utilizing 4-pyrrolidinopyridine as an effective achiral Lewis base. 29125760 1 48 theme N-heterocycle-fused-β-lactones 237:266 arg1 synthesis 224:232 the diastereo- and enantioselective synthesis 188:232 the diastereo- and enantioselective synthesis of N-heterocycle-fused-β-lactones from N-linked ketoacids 188:290 The utility of the nucleophile-catalyzed (Lewis base) aldol lactonization (NCAL) process for the diastereo- and enantioselective synthesis of N-heterocycle-fused-β-lactones from N-linked ketoacids is described. 29125760 0 49 theme β-Lactones 83:92 arg1 Synthesis 32:40 Diastereo- and Enantioselective Synthesis 0:40 Diastereo- and Enantioselective Synthesis of Bi- and Tricyclic N-Heterocycle-Fused β-Lactones 0:92 Diastereo- and Enantioselective Synthesis of Bi- and Tricyclic N-Heterocycle-Fused β-Lactones. 29125760 4 50 dep products 859:866 arg1 enamine 926:932 a bicyclic enamine 915:932 a bicyclic enamine derived from in situ decarboxylation of the diastereomeric tricyclic β-lactone 915:1011 An unusual diastereodivergent NCAL process was discovered that leads to two different products; a tricyclic N-heterocycle-fused β-lactone and a bicyclic enamine derived from in situ decarboxylation of the diastereomeric tricyclic β-lactone. 29125760 4 50 dep products 859:866 arg1 β-lactone 901:909 a tricyclic N-heterocycle-fused β-lactone 869:909 a tricyclic N-heterocycle-fused β-lactone 869:909 An unusual diastereodivergent NCAL process was discovered that leads to two different products; a tricyclic N-heterocycle-fused β-lactone and a bicyclic enamine derived from in situ decarboxylation of the diastereomeric tricyclic β-lactone. 29125760 4 50 dep products 859:866 arg1 products 859:866 two different products 845:866 two different products; a tricyclic N-heterocycle-fused β-lactone and a bicyclic enamine derived from in situ decarboxylation of the diastereomeric tricyclic β-lactone 845:1011 An unusual diastereodivergent NCAL process was discovered that leads to two different products; a tricyclic N-heterocycle-fused β-lactone and a bicyclic enamine derived from in situ decarboxylation of the diastereomeric tricyclic β-lactone. 29125760 1 51 theme aldol 149:153 arg1 process 176:182 the nucleophile-catalyzed (Lewis base) aldol lactonization (NCAL) process 110:182 the nucleophile-catalyzed (Lewis base) aldol lactonization (NCAL) process 110:182 The utility of the nucleophile-catalyzed (Lewis base) aldol lactonization (NCAL) process for the diastereo- and enantioselective synthesis of N-heterocycle-fused-β-lactones from N-linked ketoacids is described. 29125760 1 52 theme process 176:182 arg1 utility 99:105 The utility 95:105 The utility of the nucleophile-catalyzed (Lewis base) aldol lactonization (NCAL) process for the diastereo- and enantioselective synthesis of N-heterocycle-fused-β-lactones from N-linked ketoacids 95:290 The utility of the nucleophile-catalyzed (Lewis base) aldol lactonization (NCAL) process for the diastereo- and enantioselective synthesis of N-heterocycle-fused-β-lactones from N-linked ketoacids is described. 29125760 0 53 theme N-Heterocycle-Fused 63:81 arg1 β-Lactones 83:92 Tricyclic N-Heterocycle-Fused β-Lactones 53:92 Tricyclic N-Heterocycle-Fused β-Lactones 53:92 Diastereo- and Enantioselective Synthesis of Bi- and Tricyclic N-Heterocycle-Fused β-Lactones. 29125760 3 54 theme high 735:738 arg1 er 768:769 up to >99:1 er 756:769 up to >99:1 er 756:769 A catalytic, enantioselective version of this NCAL process using isothiourea catalysts provided access to bicyclic β-lactone-fused, N-heterocycles in moderate to good yields (up to 80%) with high enantiocontrol (up to >99:1 er). 29125760 3 54 theme high 735:738 arg1 enantiocontrol 740:753 high enantiocontrol 735:753 high enantiocontrol (up to >99:1 er) 735:770 A catalytic, enantioselective version of this NCAL process using isothiourea catalysts provided access to bicyclic β-lactone-fused, N-heterocycles in moderate to good yields (up to 80%) with high enantiocontrol (up to >99:1 er). 29125760 1 55 theme lactonization 155:167 arg1 process 176:182 the nucleophile-catalyzed (Lewis base) aldol lactonization (NCAL) process 110:182 the nucleophile-catalyzed (Lewis base) aldol lactonization (NCAL) process 110:182 The utility of the nucleophile-catalyzed (Lewis base) aldol lactonization (NCAL) process for the diastereo- and enantioselective synthesis of N-heterocycle-fused-β-lactones from N-linked ketoacids is described. 29125760 1 56 theme N-linked 273:280 arg1 ketoacids 282:290 N-linked ketoacids 273:290 N-linked ketoacids 273:290 The utility of the nucleophile-catalyzed (Lewis base) aldol lactonization (NCAL) process for the diastereo- and enantioselective synthesis of N-heterocycle-fused-β-lactones from N-linked ketoacids is described. 29019220 2 0 dep optimized 162:170 arg1 codon 156:160 codon 156:160 codon 156:160 A codon optimized nuclease gene (SNU) from Northern Shrimps was inserted into pPICZα A vector, and expressed extracellularly in strain SMD1168H. 29019220 0 1 from expression 11:20 arg1 pastoris 80:87 Pichia pastoris 73:87 Pichia pastoris 73:87 [Secretory expression and characterization of heat sensitive nuclease in Pichia pastoris]. 29019220 5 2 theme N-linked 570:577 arg1 this 560:563 this 560:563 this 560:563 SDS-PAGE electrophoresis demonstrated that this is a N-linked glycoprotein of 50 kDa. 29019220 5 2 theme N-linked 570:577 arg1 glycoprotein 579:590 a N-linked glycoprotein 568:590 a N-linked glycoprotein of 50 kDa 568:600 SDS-PAGE electrophoresis demonstrated that this is a N-linked glycoprotein of 50 kDa. 29019220 4 3 theme 1 457:457 arg1 % 458:458 % 458:458 % 458:458 SNU was highly expressed and stable after 1% methanol induction for 72 h, yield reached 1.4×10⁵ U/mL. 29019220 2 4 from Shrimps 206:212 arg1 SNU 187:189 SNU 187:189 SNU 187:189 A codon optimized nuclease gene (SNU) from Northern Shrimps was inserted into pPICZα A vector, and expressed extracellularly in strain SMD1168H. 29019220 2 4 from Shrimps 206:212 arg1 gene 181:184 A codon optimized nuclease gene 154:184 A codon optimized nuclease gene (SNU) from Northern Shrimps 154:212 A codon optimized nuclease gene (SNU) from Northern Shrimps was inserted into pPICZα A vector, and expressed extracellularly in strain SMD1168H. 29019220 5 5 link N-linked 570:577 arg1 this 560:563 this 560:563 this 560:563 SDS-PAGE electrophoresis demonstrated that this is a N-linked glycoprotein of 50 kDa. 29019220 5 5 link N-linked 570:577 arg1 glycoprotein 579:590 a N-linked glycoprotein 568:590 a N-linked glycoprotein of 50 kDa 568:600 SDS-PAGE electrophoresis demonstrated that this is a N-linked glycoprotein of 50 kDa. 29019220 3 6 theme multi-copy 315:324 arg1 strain 338:343 multi-copy recombinant strain 315:343 multi-copy recombinant strain 315:343 On the basis of multi-copy recombinant strain, we further optimized the expression condition and characterized SNU. 29019220 7 7 from analysis 746:753 arg1 activity 771:778 the nuclease activity 758:778 the nuclease activity 758:778 Functional analysis on the nuclease activity indicated that it was stimulated by bivalent iron, such as Ca²⁺, Mn²⁺, Co²⁺ and Mg²⁺, but inhibited by Zn²⁺, Cu²⁺ and high salt. 29019220 7 8 theme bivalent 816:823 arg1 iron 825:828 bivalent iron 816:828 bivalent iron 816:828 Functional analysis on the nuclease activity indicated that it was stimulated by bivalent iron, such as Ca²⁺, Mn²⁺, Co²⁺ and Mg²⁺, but inhibited by Zn²⁺, Cu²⁺ and high salt. 29019220 3 9 theme recombinant 326:336 arg1 strain 338:343 multi-copy recombinant strain 315:343 multi-copy recombinant strain 315:343 On the basis of multi-copy recombinant strain, we further optimized the expression condition and characterized SNU. 29019220 4 10 theme methanol 460:467 arg1 induction 469:477 1% methanol induction 457:477 1% methanol induction 457:477 SNU was highly expressed and stable after 1% methanol induction for 72 h, yield reached 1.4×10⁵ U/mL. 29019220 5 11 theme kDa 598:600 arg1 this 560:563 this 560:563 this 560:563 SDS-PAGE electrophoresis demonstrated that this is a N-linked glycoprotein of 50 kDa. 29019220 5 11 theme kDa 598:600 arg1 glycoprotein 579:590 a N-linked glycoprotein 568:590 a N-linked glycoprotein of 50 kDa 568:600 SDS-PAGE electrophoresis demonstrated that this is a N-linked glycoprotein of 50 kDa. 29019220 4 12 theme % 458:458 arg1 induction 469:477 1% methanol induction 457:477 1% methanol induction 457:477 SNU was highly expressed and stable after 1% methanol induction for 72 h, yield reached 1.4×10⁵ U/mL. 29019220 6 13 theme U/mg 729:732 arg1 activity 707:714 a specific activity 696:714 a specific activity of 6.291×10⁶ U/mg 696:732 It was purified by one step DEAE Sephadex chromatography to the purity of about 15 mg/L with a specific activity of 6.291×10⁶ U/mg. 29019220 7 14 theme nuclease 762:769 arg1 activity 771:778 the nuclease activity 758:778 the nuclease activity 758:778 Functional analysis on the nuclease activity indicated that it was stimulated by bivalent iron, such as Ca²⁺, Mn²⁺, Co²⁺ and Mg²⁺, but inhibited by Zn²⁺, Cu²⁺ and high salt. 29019220 6 15 theme 6.291×10⁶ 719:727 arg1 U/mg 729:732 6.291×10⁶ U/mg 719:732 6.291×10⁶ U/mg 719:732 It was purified by one step DEAE Sephadex chromatography to the purity of about 15 mg/L with a specific activity of 6.291×10⁶ U/mg. 29019220 2 16 theme strain 282:287 arg1 SMD1168H 289:296 strain SMD1168H 282:296 strain SMD1168H 282:296 A codon optimized nuclease gene (SNU) from Northern Shrimps was inserted into pPICZα A vector, and expressed extracellularly in strain SMD1168H. 29019220 6 17 theme Sephadex 636:643 arg1 chromatography 645:658 one step DEAE Sephadex chromatography 622:658 one step DEAE Sephadex chromatography to the purity of about 15 mg/L with a specific activity of 6.291×10⁶ U/mg 622:732 It was purified by one step DEAE Sephadex chromatography to the purity of about 15 mg/L with a specific activity of 6.291×10⁶ U/mg. 29019220 7 18 theme high 898:901 arg1 salt 903:906 high salt 898:906 high salt 898:906 Functional analysis on the nuclease activity indicated that it was stimulated by bivalent iron, such as Ca²⁺, Mn²⁺, Co²⁺ and Mg²⁺, but inhibited by Zn²⁺, Cu²⁺ and high salt. 29019220 6 19 theme specific 698:705 arg1 activity 707:714 a specific activity 696:714 a specific activity of 6.291×10⁶ U/mg 696:732 It was purified by one step DEAE Sephadex chromatography to the purity of about 15 mg/L with a specific activity of 6.291×10⁶ U/mg. 29019220 6 20 theme DEAE 631:634 arg1 chromatography 645:658 one step DEAE Sephadex chromatography 622:658 one step DEAE Sephadex chromatography to the purity of about 15 mg/L with a specific activity of 6.291×10⁶ U/mg 622:732 It was purified by one step DEAE Sephadex chromatography to the purity of about 15 mg/L with a specific activity of 6.291×10⁶ U/mg. 29019220 2 21 theme nuclease 172:179 arg1 SNU 187:189 SNU 187:189 SNU 187:189 A codon optimized nuclease gene (SNU) from Northern Shrimps was inserted into pPICZα A vector, and expressed extracellularly in strain SMD1168H. 29019220 2 21 theme nuclease 172:179 arg1 gene 181:184 A codon optimized nuclease gene 154:184 A codon optimized nuclease gene (SNU) from Northern Shrimps 154:212 A codon optimized nuclease gene (SNU) from Northern Shrimps was inserted into pPICZα A vector, and expressed extracellularly in strain SMD1168H. 29019220 6 22 theme step 626:629 arg1 chromatography 645:658 one step DEAE Sephadex chromatography 622:658 one step DEAE Sephadex chromatography to the purity of about 15 mg/L with a specific activity of 6.291×10⁶ U/mg 622:732 It was purified by one step DEAE Sephadex chromatography to the purity of about 15 mg/L with a specific activity of 6.291×10⁶ U/mg. 29019220 2 23 theme optimized 162:170 arg1 SNU 187:189 SNU 187:189 SNU 187:189 A codon optimized nuclease gene (SNU) from Northern Shrimps was inserted into pPICZα A vector, and expressed extracellularly in strain SMD1168H. 29019220 2 23 theme optimized 162:170 arg1 gene 181:184 A codon optimized nuclease gene 154:184 A codon optimized nuclease gene (SNU) from Northern Shrimps 154:212 A codon optimized nuclease gene (SNU) from Northern Shrimps was inserted into pPICZα A vector, and expressed extracellularly in strain SMD1168H. 29019220 3 24 theme expression 371:380 arg1 condition 382:390 the expression condition 367:390 the expression condition 367:390 On the basis of multi-copy recombinant strain, we further optimized the expression condition and characterized SNU. 29019220 7 25 theme Functional 735:744 arg1 analysis 746:753 Functional analysis 735:753 Functional analysis on the nuclease activity 735:778 Functional analysis on the nuclease activity indicated that it was stimulated by bivalent iron, such as Ca²⁺, Mn²⁺, Co²⁺ and Mg²⁺, but inhibited by Zn²⁺, Cu²⁺ and high salt. 29019220 6 26 with chromatography 645:658 arg1 activity 707:714 a specific activity 696:714 a specific activity of 6.291×10⁶ U/mg 696:732 It was purified by one step DEAE Sephadex chromatography to the purity of about 15 mg/L with a specific activity of 6.291×10⁶ U/mg. 29019220 1 27 theme important 107:115 arg1 Nucleases 91:99 Nucleases 91:99 Nucleases 91:99 Nucleases is an important enzyme widely used in biotechnology. 29019220 1 27 theme important 107:115 arg1 enzyme 117:122 an important enzyme 104:122 an important enzyme widely used in biotechnology 104:151 Nucleases is an important enzyme widely used in biotechnology. 29019220 0 28 theme sensitive 51:59 arg1 nuclease 61:68 heat sensitive nuclease 46:68 heat sensitive nuclease 46:68 [Secretory expression and characterization of heat sensitive nuclease in Pichia pastoris]. 29019220 4 29 theme 1.4×10⁵ 503:509 arg1 U/mL 511:514 1.4×10⁵ U/mL 503:514 1.4×10⁵ U/mL 503:514 SNU was highly expressed and stable after 1% methanol induction for 72 h, yield reached 1.4×10⁵ U/mL. 29019220 2 30 theme Northern 197:204 arg1 Shrimps 206:212 Northern Shrimps 197:212 Northern Shrimps 197:212 A codon optimized nuclease gene (SNU) from Northern Shrimps was inserted into pPICZα A vector, and expressed extracellularly in strain SMD1168H. 29019220 5 31 theme SDS-PAGE 517:524 arg1 electrophoresis 526:540 SDS-PAGE electrophoresis 517:540 SDS-PAGE electrophoresis 517:540 SDS-PAGE electrophoresis demonstrated that this is a N-linked glycoprotein of 50 kDa. 29019220 3 32 dep strain 338:343 arg1 basis 306:310 basis 306:310 basis 306:310 On the basis of multi-copy recombinant strain, we further optimized the expression condition and characterized SNU. 29019220 3 32 dep strain 338:343 arg1 the 302:304 the 302:304 the 302:304 On the basis of multi-copy recombinant strain, we further optimized the expression condition and characterized SNU. 29019220 2 33 theme A 239:239 arg1 vector 241:246 pPICZα A vector 232:246 pPICZα A vector 232:246 A codon optimized nuclease gene (SNU) from Northern Shrimps was inserted into pPICZα A vector, and expressed extracellularly in strain SMD1168H. 29019220 0 34 theme Pichia 73:78 arg1 pastoris 80:87 Pichia pastoris 73:87 Pichia pastoris 73:87 [Secretory expression and characterization of heat sensitive nuclease in Pichia pastoris]. 29019220 2 35 theme pPICZα 232:237 arg1 vector 241:246 pPICZα A vector 232:246 pPICZα A vector 232:246 A codon optimized nuclease gene (SNU) from Northern Shrimps was inserted into pPICZα A vector, and expressed extracellularly in strain SMD1168H. 29019220 6 36 theme mg/L 686:689 arg1 purity 667:672 the purity 663:672 the purity of about 15 mg/L 663:689 It was purified by one step DEAE Sephadex chromatography to the purity of about 15 mg/L with a specific activity of 6.291×10⁶ U/mg. 29019220 0 37 theme nuclease 61:68 arg1 characterization 26:41 characterization 26:41 characterization 26:41 [Secretory expression and characterization of heat sensitive nuclease in Pichia pastoris]. 29019220 0 37 theme nuclease 61:68 arg1 expression 11:20 expression 11:20 expression 11:20 [Secretory expression and characterization of heat sensitive nuclease in Pichia pastoris]. 29019220 0 38 from characterization 26:41 arg1 pastoris 80:87 Pichia pastoris 73:87 Pichia pastoris 73:87 [Secretory expression and characterization of heat sensitive nuclease in Pichia pastoris]. 29019220 5 39 gly glycoprotein 579:590 arg1 this 560:563 this 560:563 this 560:563 SDS-PAGE electrophoresis demonstrated that this is a N-linked glycoprotein of 50 kDa. 29019220 5 39 gly glycoprotein 579:590 arg1 glycoprotein 579:590 a N-linked glycoprotein 568:590 a N-linked glycoprotein of 50 kDa 568:600 SDS-PAGE electrophoresis demonstrated that this is a N-linked glycoprotein of 50 kDa. 24949924 0 0 theme Phase 77:81 arg1 State 83:87 Phase State 77:87 Phase State 77:87 N-Acyl Chain in Ceramide and Sphingomyelin Determines Their Mixing Behavior, Phase State, and Surface Topography in Langmuir Films. 24949924 2 1 theme mixing 370:375 arg1 behavior 377:384 the mixing behavior 366:384 the mixing behavior of different sphingolipids 366:411 The effect of length and unsaturation of the N-acyl chain on the mixing behavior of different sphingolipids has scarcely been studied, and in this work this issue is addressed employing Langmuir monolayers at the air-water interface, in order to assess the surface mixing in binary mixtures of different species of sphingomyelins and ceramides. 24949924 2 2 theme length 319:324 arg1 effect 309:314 The effect 305:314 The effect of length and unsaturation of the N-acyl chain on the mixing behavior of different sphingolipids 305:411 The effect of length and unsaturation of the N-acyl chain on the mixing behavior of different sphingolipids has scarcely been studied, and in this work this issue is addressed employing Langmuir monolayers at the air-water interface, in order to assess the surface mixing in binary mixtures of different species of sphingomyelins and ceramides. 24949924 3 3 theme surface 775:781 arg1 topography 783:792 surface topography 775:792 surface topography 775:792 The dependence on the monolayer composition of the mean molecular area, perpendicular dipole moment, domain segregation, and surface topography, as well as the film elasticity and optical thickness were studied. 24949924 0 4 from Chain 7:11 arg1 Sphingomyelin 29:41 Sphingomyelin 29:41 Sphingomyelin 29:41 N-Acyl Chain in Ceramide and Sphingomyelin Determines Their Mixing Behavior, Phase State, and Surface Topography in Langmuir Films. 24949924 0 4 from Chain 7:11 arg1 Ceramide 16:23 Ceramide 16:23 Ceramide 16:23 N-Acyl Chain in Ceramide and Sphingomyelin Determines Their Mixing Behavior, Phase State, and Surface Topography in Langmuir Films. 24949924 1 5 link N-linked 235:242 arg1 chain 255:259 a N-linked fatty acyl chain 233:259 a N-linked fatty acyl chain whose quality depends on the membrane type 233:302 Sphingolipids are membrane lipids composed by a long chain aminediol base, usually sphingosine, with a N-linked fatty acyl chain whose quality depends on the membrane type. 24949924 1 6 theme membrane 150:157 arg1 Sphingolipids 132:144 Sphingolipids 132:144 Sphingolipids 132:144 Sphingolipids are membrane lipids composed by a long chain aminediol base, usually sphingosine, with a N-linked fatty acyl chain whose quality depends on the membrane type. 24949924 1 6 theme membrane 150:157 arg1 lipids 159:164 membrane lipids 150:164 membrane lipids composed by a long chain aminediol base, usually sphingosine, with a N-linked fatty acyl chain whose quality depends on the membrane type 150:302 Sphingolipids are membrane lipids composed by a long chain aminediol base, usually sphingosine, with a N-linked fatty acyl chain whose quality depends on the membrane type. 24949924 4 7 theme chain 1041:1045 arg1 ordering 1047:1054 increased acyl chain ordering 1026:1054 increased acyl chain ordering 1026:1054 The results indicate that composition-dependent favorable interactions among sphingomyelin and ceramide occur as a consequence of complementary lateral packing and increased acyl chain ordering; the phase state of the components appears as a major factor determining miscibility among sphingomyelins and ceramides even in cases where the lipids have a considerable hydrocarbon chain length mismatch. 24949924 3 8 theme topography 783:792 arg1 composition 682:692 the monolayer composition 668:692 the monolayer composition of the mean molecular area, perpendicular dipole moment, domain segregation, and surface topography, as well as the film elasticity and optical thickness 668:846 The dependence on the monolayer composition of the mean molecular area, perpendicular dipole moment, domain segregation, and surface topography, as well as the film elasticity and optical thickness were studied. 24949924 4 9 theme composition-dependent 888:908 arg1 interactions 920:931 composition-dependent favorable interactions 888:931 composition-dependent favorable interactions among sphingomyelin and ceramide 888:964 The results indicate that composition-dependent favorable interactions among sphingomyelin and ceramide occur as a consequence of complementary lateral packing and increased acyl chain ordering; the phase state of the components appears as a major factor determining miscibility among sphingomyelins and ceramides even in cases where the lipids have a considerable hydrocarbon chain length mismatch. 24949924 4 10 theme considerable 1214:1225 arg1 mismatch 1252:1259 a considerable hydrocarbon chain length mismatch 1212:1259 a considerable hydrocarbon chain length mismatch 1212:1259 The results indicate that composition-dependent favorable interactions among sphingomyelin and ceramide occur as a consequence of complementary lateral packing and increased acyl chain ordering; the phase state of the components appears as a major factor determining miscibility among sphingomyelins and ceramides even in cases where the lipids have a considerable hydrocarbon chain length mismatch. 24949924 3 11 theme film 810:813 arg1 elasticity 815:824 the film elasticity 806:824 the film elasticity 806:824 The dependence on the monolayer composition of the mean molecular area, perpendicular dipole moment, domain segregation, and surface topography, as well as the film elasticity and optical thickness were studied. 24949924 1 12 theme N-linked 235:242 arg1 chain 255:259 a N-linked fatty acyl chain 233:259 a N-linked fatty acyl chain whose quality depends on the membrane type 233:302 Sphingolipids are membrane lipids composed by a long chain aminediol base, usually sphingosine, with a N-linked fatty acyl chain whose quality depends on the membrane type. 24949924 3 13 theme monolayer 672:680 arg1 composition 682:692 the monolayer composition 668:692 the monolayer composition of the mean molecular area, perpendicular dipole moment, domain segregation, and surface topography, as well as the film elasticity and optical thickness 668:846 The dependence on the monolayer composition of the mean molecular area, perpendicular dipole moment, domain segregation, and surface topography, as well as the film elasticity and optical thickness were studied. 24949924 2 14 from effect 309:314 arg1 behavior 377:384 the mixing behavior 366:384 the mixing behavior of different sphingolipids 366:411 The effect of length and unsaturation of the N-acyl chain on the mixing behavior of different sphingolipids has scarcely been studied, and in this work this issue is addressed employing Langmuir monolayers at the air-water interface, in order to assess the surface mixing in binary mixtures of different species of sphingomyelins and ceramides. 24949924 1 15 theme fatty 244:248 arg1 chain 255:259 a N-linked fatty acyl chain 233:259 a N-linked fatty acyl chain whose quality depends on the membrane type 233:302 Sphingolipids are membrane lipids composed by a long chain aminediol base, usually sphingosine, with a N-linked fatty acyl chain whose quality depends on the membrane type. 24949924 0 16 theme Surface 94:100 arg1 Topography 102:111 Surface Topography 94:111 Surface Topography 94:111 N-Acyl Chain in Ceramide and Sphingomyelin Determines Their Mixing Behavior, Phase State, and Surface Topography in Langmuir Films. 24949924 2 17 theme binary 580:585 arg1 mixtures 587:594 binary mixtures 580:594 binary mixtures of different species of sphingomyelins and ceramides 580:647 The effect of length and unsaturation of the N-acyl chain on the mixing behavior of different sphingolipids has scarcely been studied, and in this work this issue is addressed employing Langmuir monolayers at the air-water interface, in order to assess the surface mixing in binary mixtures of different species of sphingomyelins and ceramides. 24949924 4 18 theme acyl 1036:1039 arg1 ordering 1047:1054 increased acyl chain ordering 1026:1054 increased acyl chain ordering 1026:1054 The results indicate that composition-dependent favorable interactions among sphingomyelin and ceramide occur as a consequence of complementary lateral packing and increased acyl chain ordering; the phase state of the components appears as a major factor determining miscibility among sphingomyelins and ceramides even in cases where the lipids have a considerable hydrocarbon chain length mismatch. 24949924 2 19 theme chain 357:361 arg1 length 319:324 length 319:324 length 319:324 The effect of length and unsaturation of the N-acyl chain on the mixing behavior of different sphingolipids has scarcely been studied, and in this work this issue is addressed employing Langmuir monolayers at the air-water interface, in order to assess the surface mixing in binary mixtures of different species of sphingomyelins and ceramides. 24949924 2 19 theme chain 357:361 arg1 unsaturation 330:341 unsaturation 330:341 unsaturation 330:341 The effect of length and unsaturation of the N-acyl chain on the mixing behavior of different sphingolipids has scarcely been studied, and in this work this issue is addressed employing Langmuir monolayers at the air-water interface, in order to assess the surface mixing in binary mixtures of different species of sphingomyelins and ceramides. 24949924 4 20 contain have 1207:1210 arg2 mismatch 1252:1259 a considerable hydrocarbon chain length mismatch 1212:1259 a considerable hydrocarbon chain length mismatch 1212:1259 The results indicate that composition-dependent favorable interactions among sphingomyelin and ceramide occur as a consequence of complementary lateral packing and increased acyl chain ordering; the phase state of the components appears as a major factor determining miscibility among sphingomyelins and ceramides even in cases where the lipids have a considerable hydrocarbon chain length mismatch. 24949924 4 20 contain have 1207:1210 arg1 lipids 1200:1205 the lipids 1196:1205 the lipids 1196:1205 The results indicate that composition-dependent favorable interactions among sphingomyelin and ceramide occur as a consequence of complementary lateral packing and increased acyl chain ordering; the phase state of the components appears as a major factor determining miscibility among sphingomyelins and ceramides even in cases where the lipids have a considerable hydrocarbon chain length mismatch. 24949924 2 21 theme sphingolipids 399:411 arg1 behavior 377:384 the mixing behavior 366:384 the mixing behavior of different sphingolipids 366:411 The effect of length and unsaturation of the N-acyl chain on the mixing behavior of different sphingolipids has scarcely been studied, and in this work this issue is addressed employing Langmuir monolayers at the air-water interface, in order to assess the surface mixing in binary mixtures of different species of sphingomyelins and ceramides. 24949924 3 22 theme optical 830:836 arg1 thickness 838:846 optical thickness 830:846 optical thickness 830:846 The dependence on the monolayer composition of the mean molecular area, perpendicular dipole moment, domain segregation, and surface topography, as well as the film elasticity and optical thickness were studied. 24949924 2 23 theme N-acyl 350:355 arg1 chain 357:361 the N-acyl chain 346:361 the N-acyl chain 346:361 The effect of length and unsaturation of the N-acyl chain on the mixing behavior of different sphingolipids has scarcely been studied, and in this work this issue is addressed employing Langmuir monolayers at the air-water interface, in order to assess the surface mixing in binary mixtures of different species of sphingomyelins and ceramides. 24949924 4 24 theme complementary 992:1004 arg1 packing 1014:1020 complementary lateral packing 992:1020 complementary lateral packing 992:1020 The results indicate that composition-dependent favorable interactions among sphingomyelin and ceramide occur as a consequence of complementary lateral packing and increased acyl chain ordering; the phase state of the components appears as a major factor determining miscibility among sphingomyelins and ceramides even in cases where the lipids have a considerable hydrocarbon chain length mismatch. 24949924 2 25 theme surface 562:568 arg1 mixing 570:575 the surface mixing 558:575 the surface mixing in binary mixtures of different species of sphingomyelins and ceramides 558:647 The effect of length and unsaturation of the N-acyl chain on the mixing behavior of different sphingolipids has scarcely been studied, and in this work this issue is addressed employing Langmuir monolayers at the air-water interface, in order to assess the surface mixing in binary mixtures of different species of sphingomyelins and ceramides. 24949924 2 26 theme sphingomyelins 620:633 arg1 species 609:615 different species 599:615 different species of sphingomyelins and ceramides 599:647 The effect of length and unsaturation of the N-acyl chain on the mixing behavior of different sphingolipids has scarcely been studied, and in this work this issue is addressed employing Langmuir monolayers at the air-water interface, in order to assess the surface mixing in binary mixtures of different species of sphingomyelins and ceramides. 24949924 3 27 theme thickness 838:846 arg1 composition 682:692 the monolayer composition 668:692 the monolayer composition of the mean molecular area, perpendicular dipole moment, domain segregation, and surface topography, as well as the film elasticity and optical thickness 668:846 The dependence on the monolayer composition of the mean molecular area, perpendicular dipole moment, domain segregation, and surface topography, as well as the film elasticity and optical thickness were studied. 24949924 0 28 theme N-Acyl 0:5 arg1 Chain 7:11 N-Acyl Chain 0:11 N-Acyl Chain in Ceramide and Sphingomyelin 0:41 N-Acyl Chain in Ceramide and Sphingomyelin Determines Their Mixing Behavior, Phase State, and Surface Topography in Langmuir Films. 24949924 1 29 theme acyl 250:253 arg1 chain 255:259 a N-linked fatty acyl chain 233:259 a N-linked fatty acyl chain whose quality depends on the membrane type 233:302 Sphingolipids are membrane lipids composed by a long chain aminediol base, usually sphingosine, with a N-linked fatty acyl chain whose quality depends on the membrane type. 24949924 3 30 theme mean 701:704 arg1 area 716:719 the mean molecular area 697:719 the mean molecular area 697:719 The dependence on the monolayer composition of the mean molecular area, perpendicular dipole moment, domain segregation, and surface topography, as well as the film elasticity and optical thickness were studied. 24949924 2 31 theme different 389:397 arg1 sphingolipids 399:411 different sphingolipids 389:411 different sphingolipids 389:411 The effect of length and unsaturation of the N-acyl chain on the mixing behavior of different sphingolipids has scarcely been studied, and in this work this issue is addressed employing Langmuir monolayers at the air-water interface, in order to assess the surface mixing in binary mixtures of different species of sphingomyelins and ceramides. 24949924 3 32 theme molecular 706:714 arg1 area 716:719 the mean molecular area 697:719 the mean molecular area 697:719 The dependence on the monolayer composition of the mean molecular area, perpendicular dipole moment, domain segregation, and surface topography, as well as the film elasticity and optical thickness were studied. 24949924 2 33 theme species 609:615 arg1 mixtures 587:594 binary mixtures 580:594 binary mixtures of different species of sphingomyelins and ceramides 580:647 The effect of length and unsaturation of the N-acyl chain on the mixing behavior of different sphingolipids has scarcely been studied, and in this work this issue is addressed employing Langmuir monolayers at the air-water interface, in order to assess the surface mixing in binary mixtures of different species of sphingomyelins and ceramides. 24949924 2 34 theme different 599:607 arg1 species 609:615 different species 599:615 different species of sphingomyelins and ceramides 599:647 The effect of length and unsaturation of the N-acyl chain on the mixing behavior of different sphingolipids has scarcely been studied, and in this work this issue is addressed employing Langmuir monolayers at the air-water interface, in order to assess the surface mixing in binary mixtures of different species of sphingomyelins and ceramides. 24949924 1 35 theme long 180:183 arg1 sphingosine 215:225 sphingosine 215:225 usually sphingosine 207:225 Sphingolipids are membrane lipids composed by a long chain aminediol base, usually sphingosine, with a N-linked fatty acyl chain whose quality depends on the membrane type. 24949924 1 35 theme long 180:183 arg1 base 201:204 a long chain aminediol base 178:204 a long chain aminediol base 178:204 Sphingolipids are membrane lipids composed by a long chain aminediol base, usually sphingosine, with a N-linked fatty acyl chain whose quality depends on the membrane type. 24949924 4 36 theme lateral 1006:1012 arg1 packing 1014:1020 complementary lateral packing 992:1020 complementary lateral packing 992:1020 The results indicate that composition-dependent favorable interactions among sphingomyelin and ceramide occur as a consequence of complementary lateral packing and increased acyl chain ordering; the phase state of the components appears as a major factor determining miscibility among sphingomyelins and ceramides even in cases where the lipids have a considerable hydrocarbon chain length mismatch. 24949924 1 37 with base 201:204 arg1 chain 255:259 a N-linked fatty acyl chain 233:259 a N-linked fatty acyl chain whose quality depends on the membrane type 233:302 Sphingolipids are membrane lipids composed by a long chain aminediol base, usually sphingosine, with a N-linked fatty acyl chain whose quality depends on the membrane type. 24949924 4 38 theme components 1080:1089 arg1 state 1067:1071 the phase state 1057:1071 the phase state of the components 1057:1089 The results indicate that composition-dependent favorable interactions among sphingomyelin and ceramide occur as a consequence of complementary lateral packing and increased acyl chain ordering; the phase state of the components appears as a major factor determining miscibility among sphingomyelins and ceramides even in cases where the lipids have a considerable hydrocarbon chain length mismatch. 24949924 1 39 theme chain 185:189 arg1 sphingosine 215:225 sphingosine 215:225 usually sphingosine 207:225 Sphingolipids are membrane lipids composed by a long chain aminediol base, usually sphingosine, with a N-linked fatty acyl chain whose quality depends on the membrane type. 24949924 1 39 theme chain 185:189 arg1 base 201:204 a long chain aminediol base 178:204 a long chain aminediol base 178:204 Sphingolipids are membrane lipids composed by a long chain aminediol base, usually sphingosine, with a N-linked fatty acyl chain whose quality depends on the membrane type. 24949924 2 40 theme Langmuir 491:498 arg1 monolayers 500:509 Langmuir monolayers 491:509 Langmuir monolayers 491:509 The effect of length and unsaturation of the N-acyl chain on the mixing behavior of different sphingolipids has scarcely been studied, and in this work this issue is addressed employing Langmuir monolayers at the air-water interface, in order to assess the surface mixing in binary mixtures of different species of sphingomyelins and ceramides. 24949924 4 41 theme length 1245:1250 arg1 mismatch 1252:1259 a considerable hydrocarbon chain length mismatch 1212:1259 a considerable hydrocarbon chain length mismatch 1212:1259 The results indicate that composition-dependent favorable interactions among sphingomyelin and ceramide occur as a consequence of complementary lateral packing and increased acyl chain ordering; the phase state of the components appears as a major factor determining miscibility among sphingomyelins and ceramides even in cases where the lipids have a considerable hydrocarbon chain length mismatch. 24949924 1 42 theme aminediol 191:199 arg1 sphingosine 215:225 sphingosine 215:225 usually sphingosine 207:225 Sphingolipids are membrane lipids composed by a long chain aminediol base, usually sphingosine, with a N-linked fatty acyl chain whose quality depends on the membrane type. 24949924 1 42 theme aminediol 191:199 arg1 base 201:204 a long chain aminediol base 178:204 a long chain aminediol base 178:204 Sphingolipids are membrane lipids composed by a long chain aminediol base, usually sphingosine, with a N-linked fatty acyl chain whose quality depends on the membrane type. 24949924 3 43 theme perpendicular 722:734 arg1 moment 743:748 perpendicular dipole moment 722:748 perpendicular dipole moment 722:748 The dependence on the monolayer composition of the mean molecular area, perpendicular dipole moment, domain segregation, and surface topography, as well as the film elasticity and optical thickness were studied. 24949924 0 44 theme Langmuir 116:123 arg1 Films 125:129 Langmuir Films 116:129 Langmuir Films 116:129 N-Acyl Chain in Ceramide and Sphingomyelin Determines Their Mixing Behavior, Phase State, and Surface Topography in Langmuir Films. 24949924 0 45 from Behavior 67:74 arg1 Films 125:129 Langmuir Films 116:129 Langmuir Films 116:129 N-Acyl Chain in Ceramide and Sphingomyelin Determines Their Mixing Behavior, Phase State, and Surface Topography in Langmuir Films. 24949924 4 46 theme packing 1014:1020 arg1 consequence 977:987 a consequence 975:987 a consequence of complementary lateral packing and increased acyl chain ordering 975:1054 The results indicate that composition-dependent favorable interactions among sphingomyelin and ceramide occur as a consequence of complementary lateral packing and increased acyl chain ordering; the phase state of the components appears as a major factor determining miscibility among sphingomyelins and ceramides even in cases where the lipids have a considerable hydrocarbon chain length mismatch. 24949924 2 47 from mixing 570:575 arg1 mixtures 587:594 binary mixtures 580:594 binary mixtures of different species of sphingomyelins and ceramides 580:647 The effect of length and unsaturation of the N-acyl chain on the mixing behavior of different sphingolipids has scarcely been studied, and in this work this issue is addressed employing Langmuir monolayers at the air-water interface, in order to assess the surface mixing in binary mixtures of different species of sphingomyelins and ceramides. 24949924 3 48 theme dipole 736:741 arg1 moment 743:748 perpendicular dipole moment 722:748 perpendicular dipole moment 722:748 The dependence on the monolayer composition of the mean molecular area, perpendicular dipole moment, domain segregation, and surface topography, as well as the film elasticity and optical thickness were studied. 24949924 3 49 from dependence 654:663 arg1 composition 682:692 the monolayer composition 668:692 the monolayer composition of the mean molecular area, perpendicular dipole moment, domain segregation, and surface topography, as well as the film elasticity and optical thickness 668:846 The dependence on the monolayer composition of the mean molecular area, perpendicular dipole moment, domain segregation, and surface topography, as well as the film elasticity and optical thickness were studied. 24949924 3 50 theme area 716:719 arg1 composition 682:692 the monolayer composition 668:692 the monolayer composition of the mean molecular area, perpendicular dipole moment, domain segregation, and surface topography, as well as the film elasticity and optical thickness 668:846 The dependence on the monolayer composition of the mean molecular area, perpendicular dipole moment, domain segregation, and surface topography, as well as the film elasticity and optical thickness were studied. 24949924 4 51 theme chain 1239:1243 arg1 mismatch 1252:1259 a considerable hydrocarbon chain length mismatch 1212:1259 a considerable hydrocarbon chain length mismatch 1212:1259 The results indicate that composition-dependent favorable interactions among sphingomyelin and ceramide occur as a consequence of complementary lateral packing and increased acyl chain ordering; the phase state of the components appears as a major factor determining miscibility among sphingomyelins and ceramides even in cases where the lipids have a considerable hydrocarbon chain length mismatch. 24949924 1 52 theme membrane 290:297 arg1 type 299:302 the membrane type 286:302 the membrane type 286:302 Sphingolipids are membrane lipids composed by a long chain aminediol base, usually sphingosine, with a N-linked fatty acyl chain whose quality depends on the membrane type. 24949924 2 53 theme air-water 518:526 arg1 interface 528:536 the air-water interface 514:536 the air-water interface 514:536 The effect of length and unsaturation of the N-acyl chain on the mixing behavior of different sphingolipids has scarcely been studied, and in this work this issue is addressed employing Langmuir monolayers at the air-water interface, in order to assess the surface mixing in binary mixtures of different species of sphingomyelins and ceramides. 24949924 4 54 theme hydrocarbon 1227:1237 arg1 mismatch 1252:1259 a considerable hydrocarbon chain length mismatch 1212:1259 a considerable hydrocarbon chain length mismatch 1212:1259 The results indicate that composition-dependent favorable interactions among sphingomyelin and ceramide occur as a consequence of complementary lateral packing and increased acyl chain ordering; the phase state of the components appears as a major factor determining miscibility among sphingomyelins and ceramides even in cases where the lipids have a considerable hydrocarbon chain length mismatch. 24949924 2 55 theme ceramides 639:647 arg1 species 609:615 different species 599:615 different species of sphingomyelins and ceramides 599:647 The effect of length and unsaturation of the N-acyl chain on the mixing behavior of different sphingolipids has scarcely been studied, and in this work this issue is addressed employing Langmuir monolayers at the air-water interface, in order to assess the surface mixing in binary mixtures of different species of sphingomyelins and ceramides. 24949924 4 56 theme ordering 1047:1054 arg1 consequence 977:987 a consequence 975:987 a consequence of complementary lateral packing and increased acyl chain ordering 975:1054 The results indicate that composition-dependent favorable interactions among sphingomyelin and ceramide occur as a consequence of complementary lateral packing and increased acyl chain ordering; the phase state of the components appears as a major factor determining miscibility among sphingomyelins and ceramides even in cases where the lipids have a considerable hydrocarbon chain length mismatch. 24949924 3 57 theme domain 751:756 arg1 segregation 758:768 domain segregation 751:768 domain segregation 751:768 The dependence on the monolayer composition of the mean molecular area, perpendicular dipole moment, domain segregation, and surface topography, as well as the film elasticity and optical thickness were studied. 24949924 4 58 theme major 1104:1108 arg1 factor 1110:1115 a major factor 1102:1115 a major factor determining miscibility among sphingomyelins and ceramides even in cases where the lipids have a considerable hydrocarbon chain length mismatch 1102:1259 The results indicate that composition-dependent favorable interactions among sphingomyelin and ceramide occur as a consequence of complementary lateral packing and increased acyl chain ordering; the phase state of the components appears as a major factor determining miscibility among sphingomyelins and ceramides even in cases where the lipids have a considerable hydrocarbon chain length mismatch. 24949924 4 59 theme phase 1061:1065 arg1 state 1067:1071 the phase state 1057:1071 the phase state of the components 1057:1089 The results indicate that composition-dependent favorable interactions among sphingomyelin and ceramide occur as a consequence of complementary lateral packing and increased acyl chain ordering; the phase state of the components appears as a major factor determining miscibility among sphingomyelins and ceramides even in cases where the lipids have a considerable hydrocarbon chain length mismatch. 24949924 3 60 theme segregation 758:768 arg1 composition 682:692 the monolayer composition 668:692 the monolayer composition of the mean molecular area, perpendicular dipole moment, domain segregation, and surface topography, as well as the film elasticity and optical thickness 668:846 The dependence on the monolayer composition of the mean molecular area, perpendicular dipole moment, domain segregation, and surface topography, as well as the film elasticity and optical thickness were studied. 24949924 0 61 from State 83:87 arg1 Films 125:129 Langmuir Films 116:129 Langmuir Films 116:129 N-Acyl Chain in Ceramide and Sphingomyelin Determines Their Mixing Behavior, Phase State, and Surface Topography in Langmuir Films. 24949924 4 62 theme increased 1026:1034 arg1 ordering 1047:1054 increased acyl chain ordering 1026:1054 increased acyl chain ordering 1026:1054 The results indicate that composition-dependent favorable interactions among sphingomyelin and ceramide occur as a consequence of complementary lateral packing and increased acyl chain ordering; the phase state of the components appears as a major factor determining miscibility among sphingomyelins and ceramides even in cases where the lipids have a considerable hydrocarbon chain length mismatch. 24949924 2 63 theme unsaturation 330:341 arg1 effect 309:314 The effect 305:314 The effect of length and unsaturation of the N-acyl chain on the mixing behavior of different sphingolipids 305:411 The effect of length and unsaturation of the N-acyl chain on the mixing behavior of different sphingolipids has scarcely been studied, and in this work this issue is addressed employing Langmuir monolayers at the air-water interface, in order to assess the surface mixing in binary mixtures of different species of sphingomyelins and ceramides. 24949924 3 64 theme moment 743:748 arg1 composition 682:692 the monolayer composition 668:692 the monolayer composition of the mean molecular area, perpendicular dipole moment, domain segregation, and surface topography, as well as the film elasticity and optical thickness 668:846 The dependence on the monolayer composition of the mean molecular area, perpendicular dipole moment, domain segregation, and surface topography, as well as the film elasticity and optical thickness were studied. 24949924 0 65 theme Mixing 60:65 arg1 Behavior 67:74 Their Mixing Behavior 54:74 Their Mixing Behavior 54:74 N-Acyl Chain in Ceramide and Sphingomyelin Determines Their Mixing Behavior, Phase State, and Surface Topography in Langmuir Films. 24949924 4 66 theme favorable 910:918 arg1 interactions 920:931 composition-dependent favorable interactions 888:931 composition-dependent favorable interactions among sphingomyelin and ceramide 888:964 The results indicate that composition-dependent favorable interactions among sphingomyelin and ceramide occur as a consequence of complementary lateral packing and increased acyl chain ordering; the phase state of the components appears as a major factor determining miscibility among sphingomyelins and ceramides even in cases where the lipids have a considerable hydrocarbon chain length mismatch. 24949924 3 67 theme elasticity 815:824 arg1 composition 682:692 the monolayer composition 668:692 the monolayer composition of the mean molecular area, perpendicular dipole moment, domain segregation, and surface topography, as well as the film elasticity and optical thickness 668:846 The dependence on the monolayer composition of the mean molecular area, perpendicular dipole moment, domain segregation, and surface topography, as well as the film elasticity and optical thickness were studied. 24949924 0 68 from Topography 102:111 arg1 Films 125:129 Langmuir Films 116:129 Langmuir Films 116:129 N-Acyl Chain in Ceramide and Sphingomyelin Determines Their Mixing Behavior, Phase State, and Surface Topography in Langmuir Films. 27872474 5 0 theme glycan 617:622 arg1 traits 624:629 the other glycan traits 607:629 the other glycan traits 607:629 The influence of the other glycan traits is largely unknown, mostly due to lack of glyco-engineering tools. 27872474 8 1 gly glycoproteins 1193:1205 arg1 glycoproteins 1193:1205 other glycoproteins 1187:1205 other glycoproteins 1187:1205 Combination of these techniques enable to systematically explore the biological effect of these glycosylation traits for IgG and other glycoproteins. 27872474 1 2 theme cellular 158:165 arg1 FcγR 185:188 FcγR 185:188 FcγR 185:188 Immunoglobulin G (IgG) mediates its immune functions through complement and cellular IgG-Fc receptors (FcγR). 27872474 1 2 theme cellular 158:165 arg1 receptors 174:182 cellular IgG-Fc receptors 158:182 cellular IgG-Fc receptors (FcγR) 158:189 Immunoglobulin G (IgG) mediates its immune functions through complement and cellular IgG-Fc receptors (FcγR). 27872474 7 3 theme fucosylation 856:867 arg1 level 847:851 the level 843:851 the level of fucosylation or galactosylation 843:886 Decoy substrates were used to decrease the level of fucosylation or galactosylation, glycosyltransferases were transiently overexpressed to enhance bisection, galactosylation and sialylation and in vitro sialylation was applied for enhanced sialylation. 27872474 8 4 theme traits 1168:1173 arg1 effect 1138:1143 the biological effect 1123:1143 the biological effect of these glycosylation traits for IgG and other glycoproteins 1123:1205 Combination of these techniques enable to systematically explore the biological effect of these glycosylation traits for IgG and other glycoproteins. 27872474 5 5 theme traits 624:629 arg1 influence 594:602 The influence 590:602 The influence of the other glycan traits 590:629 The influence of the other glycan traits is largely unknown, mostly due to lack of glyco-engineering tools. 27872474 5 5 theme traits 624:629 arg1 unknown 642:648 unknown 642:648 unknown 642:648 The influence of the other glycan traits is largely unknown, mostly due to lack of glyco-engineering tools. 27872474 6 6 theme eukaryotic 786:795 arg1 cells 797:801 eukaryotic cells 786:801 eukaryotic cells 786:801 We describe general methods to produce recombinant proteins of any desired glycoform in eukaryotic cells. 27872474 1 7 theme IgG-Fc 167:172 arg1 FcγR 185:188 FcγR 185:188 FcγR 185:188 Immunoglobulin G (IgG) mediates its immune functions through complement and cellular IgG-Fc receptors (FcγR). 27872474 1 7 theme IgG-Fc 167:172 arg1 receptors 174:182 cellular IgG-Fc receptors 158:182 cellular IgG-Fc receptors (FcγR) 158:189 Immunoglobulin G (IgG) mediates its immune functions through complement and cellular IgG-Fc receptors (FcγR). 27872474 3 8 theme sialic 346:351 arg1 acid 353:356 sialic acid 346:356 sialic acid 346:356 This glycan consists of variable levels of fucose, galactose, sialic acid, and bisecting N-acetylglucosamine (bisection). 27872474 4 9 theme therapeutic 555:565 arg1 antibodies 578:587 therapeutic monoclonal antibodies 555:587 therapeutic monoclonal antibodies 555:587 Of these variations, the lack of fucose strongly enhances binding to the human FcγRIII, a finding which is currently used to improve the efficacy of therapeutic monoclonal antibodies. 27872474 3 10 theme acid 353:356 arg1 levels 317:322 variable levels 308:322 variable levels of fucose, galactose, sialic acid, and bisecting N-acetylglucosamine (bisection) 308:403 This glycan consists of variable levels of fucose, galactose, sialic acid, and bisecting N-acetylglucosamine (bisection). 27872474 4 11 used used 523:526 arg2 FcγRIII 485:491 the human FcγRIII 475:491 the human FcγRIII 475:491 Of these variations, the lack of fucose strongly enhances binding to the human FcγRIII, a finding which is currently used to improve the efficacy of therapeutic monoclonal antibodies. 27872474 4 11 used used 523:526 arg2 finding 496:502 a finding 494:502 a finding which is currently used to improve the efficacy of therapeutic monoclonal antibodies 494:587 Of these variations, the lack of fucose strongly enhances binding to the human FcγRIII, a finding which is currently used to improve the efficacy of therapeutic monoclonal antibodies. 27872474 6 12 theme glycoform 773:781 arg1 proteins 749:756 recombinant proteins 737:756 recombinant proteins of any desired glycoform in eukaryotic cells 737:801 We describe general methods to produce recombinant proteins of any desired glycoform in eukaryotic cells. 27872474 3 13 theme galactose 335:343 arg1 levels 317:322 variable levels 308:322 variable levels of fucose, galactose, sialic acid, and bisecting N-acetylglucosamine (bisection) 308:403 This glycan consists of variable levels of fucose, galactose, sialic acid, and bisecting N-acetylglucosamine (bisection). 27872474 6 14 theme desired 765:771 arg1 glycoform 773:781 any desired glycoform 761:781 any desired glycoform 761:781 We describe general methods to produce recombinant proteins of any desired glycoform in eukaryotic cells. 27872474 1 15 theme Immunoglobulin 82:95 arg1 IgG 100:102 IgG 100:102 IgG 100:102 Immunoglobulin G (IgG) mediates its immune functions through complement and cellular IgG-Fc receptors (FcγR). 27872474 1 15 theme Immunoglobulin 82:95 arg1 G 97:97 Immunoglobulin G 82:97 Immunoglobulin G (IgG) 82:103 Immunoglobulin G (IgG) mediates its immune functions through complement and cellular IgG-Fc receptors (FcγR). 27872474 8 16 theme other 1187:1191 arg1 glycoproteins 1193:1205 other glycoproteins 1187:1205 other glycoproteins 1187:1205 Combination of these techniques enable to systematically explore the biological effect of these glycosylation traits for IgG and other glycoproteins. 27872474 0 17 theme Multi-level 0:10 arg1 techniques 30:39 Multi-level glyco-engineering techniques 0:39 Multi-level glyco-engineering techniques 0:39 Multi-level glyco-engineering techniques to generate IgG with defined Fc-glycans. 27872474 0 18 theme glyco-engineering 12:28 arg1 techniques 30:39 Multi-level glyco-engineering techniques 0:39 Multi-level glyco-engineering techniques 0:39 Multi-level glyco-engineering techniques to generate IgG with defined Fc-glycans. 27872474 8 19 theme techniques 1079:1088 arg1 Combination 1058:1068 Combination 1058:1068 Combination of these techniques 1058:1088 Combination of these techniques enable to systematically explore the biological effect of these glycosylation traits for IgG and other glycoproteins. 27872474 8 20 theme glycosylation 1154:1166 arg1 traits 1168:1173 these glycosylation traits 1148:1173 these glycosylation traits 1148:1173 Combination of these techniques enable to systematically explore the biological effect of these glycosylation traits for IgG and other glycoproteins. 27872474 3 21 theme N-acetylglucosamine 373:391 arg1 levels 317:322 variable levels 308:322 variable levels of fucose, galactose, sialic acid, and bisecting N-acetylglucosamine (bisection) 308:403 This glycan consists of variable levels of fucose, galactose, sialic acid, and bisecting N-acetylglucosamine (bisection). 27872474 5 22 theme other 611:615 arg1 traits 624:629 the other glycan traits 607:629 the other glycan traits 607:629 The influence of the other glycan traits is largely unknown, mostly due to lack of glyco-engineering tools. 27872474 7 23 theme Decoy 804:808 arg1 substrates 810:819 Decoy substrates 804:819 Decoy substrates 804:819 Decoy substrates were used to decrease the level of fucosylation or galactosylation, glycosyltransferases were transiently overexpressed to enhance bisection, galactosylation and sialylation and in vitro sialylation was applied for enhanced sialylation. 27872474 6 24 theme recombinant 737:747 arg1 proteins 749:756 recombinant proteins 737:756 recombinant proteins of any desired glycoform in eukaryotic cells 737:801 We describe general methods to produce recombinant proteins of any desired glycoform in eukaryotic cells. 27872474 7 25 used used 826:829 arg2 substrates 810:819 Decoy substrates 804:819 Decoy substrates 804:819 Decoy substrates were used to decrease the level of fucosylation or galactosylation, glycosyltransferases were transiently overexpressed to enhance bisection, galactosylation and sialylation and in vitro sialylation was applied for enhanced sialylation. 27872474 6 26 from proteins 749:756 arg1 cells 797:801 eukaryotic cells 786:801 eukaryotic cells 786:801 We describe general methods to produce recombinant proteins of any desired glycoform in eukaryotic cells. 27872474 7 27 dep in 999:1000 arg1 vitro 1002:1006 vitro 1002:1006 vitro 1002:1006 Decoy substrates were used to decrease the level of fucosylation or galactosylation, glycosyltransferases were transiently overexpressed to enhance bisection, galactosylation and sialylation and in vitro sialylation was applied for enhanced sialylation. 27872474 2 28 contain contains 196:203 arg1 IgG 192:194 IgG 192:194 IgG 192:194 IgG contains an evolutionary conserved N-linked glycan at position Asn297 in the Fc-domain. 27872474 2 28 contain contains 196:203 arg2 IgG 192:194 IgG 192:194 IgG 192:194 IgG contains an evolutionary conserved N-linked glycan at position Asn297 in the Fc-domain. 27872474 2 28 contain contains 196:203 arg2 glycan 240:245 an evolutionary conserved N-linked glycan 205:245 an evolutionary conserved N-linked glycan 205:245 IgG contains an evolutionary conserved N-linked glycan at position Asn297 in the Fc-domain. 27872474 2 28 contain contains 196:203 arg1 Fc-domain 273:281 the Fc-domain 269:281 the Fc-domain 269:281 IgG contains an evolutionary conserved N-linked glycan at position Asn297 in the Fc-domain. 27872474 2 28 contain contains 196:203 arg1 position 250:257 position Asn297 250:264 position Asn297 250:264 IgG contains an evolutionary conserved N-linked glycan at position Asn297 in the Fc-domain. 27872474 5 29 theme glyco-engineering 673:689 arg1 tools 691:695 glyco-engineering tools 673:695 glyco-engineering tools 673:695 The influence of the other glycan traits is largely unknown, mostly due to lack of glyco-engineering tools. 27872474 4 30 theme fucose 439:444 arg1 lack 431:434 the lack 427:434 the lack of fucose 427:444 Of these variations, the lack of fucose strongly enhances binding to the human FcγRIII, a finding which is currently used to improve the efficacy of therapeutic monoclonal antibodies. 27872474 2 31 theme N-linked 231:238 arg1 glycan 240:245 an evolutionary conserved N-linked glycan 205:245 an evolutionary conserved N-linked glycan 205:245 IgG contains an evolutionary conserved N-linked glycan at position Asn297 in the Fc-domain. 27872474 0 32 theme defined 62:68 arg1 Fc-glycans 70:79 defined Fc-glycans 62:79 defined Fc-glycans 62:79 Multi-level glyco-engineering techniques to generate IgG with defined Fc-glycans. 27872474 5 33 theme tools 691:695 arg1 lack 665:668 lack 665:668 lack of glyco-engineering tools 665:695 The influence of the other glycan traits is largely unknown, mostly due to lack of glyco-engineering tools. 27872474 8 34 theme biological 1127:1136 arg1 effect 1138:1143 the biological effect 1123:1143 the biological effect of these glycosylation traits for IgG and other glycoproteins 1123:1205 Combination of these techniques enable to systematically explore the biological effect of these glycosylation traits for IgG and other glycoproteins. 27872474 2 35 theme conserved 221:229 arg1 glycan 240:245 an evolutionary conserved N-linked glycan 205:245 an evolutionary conserved N-linked glycan 205:245 IgG contains an evolutionary conserved N-linked glycan at position Asn297 in the Fc-domain. 27872474 3 36 theme variable 308:315 arg1 levels 317:322 variable levels 308:322 variable levels of fucose, galactose, sialic acid, and bisecting N-acetylglucosamine (bisection) 308:403 This glycan consists of variable levels of fucose, galactose, sialic acid, and bisecting N-acetylglucosamine (bisection). 27872474 2 37 theme evolutionary 208:219 arg1 glycan 240:245 an evolutionary conserved N-linked glycan 205:245 an evolutionary conserved N-linked glycan 205:245 IgG contains an evolutionary conserved N-linked glycan at position Asn297 in the Fc-domain. 27872474 1 38 theme immune 118:123 arg1 functions 125:133 its immune functions 114:133 its immune functions 114:133 Immunoglobulin G (IgG) mediates its immune functions through complement and cellular IgG-Fc receptors (FcγR). 27872474 6 39 theme general 710:716 arg1 methods 718:724 general methods 710:724 general methods 710:724 We describe general methods to produce recombinant proteins of any desired glycoform in eukaryotic cells. 27872474 4 40 theme antibodies 578:587 arg1 efficacy 543:550 the efficacy 539:550 the efficacy of therapeutic monoclonal antibodies 539:587 Of these variations, the lack of fucose strongly enhances binding to the human FcγRIII, a finding which is currently used to improve the efficacy of therapeutic monoclonal antibodies. 27872474 7 41 theme enhanced 1036:1043 arg1 sialylation 1045:1055 enhanced sialylation 1036:1055 enhanced sialylation 1036:1055 Decoy substrates were used to decrease the level of fucosylation or galactosylation, glycosyltransferases were transiently overexpressed to enhance bisection, galactosylation and sialylation and in vitro sialylation was applied for enhanced sialylation. 27872474 4 42 theme monoclonal 567:576 arg1 antibodies 578:587 therapeutic monoclonal antibodies 555:587 therapeutic monoclonal antibodies 555:587 Of these variations, the lack of fucose strongly enhances binding to the human FcγRIII, a finding which is currently used to improve the efficacy of therapeutic monoclonal antibodies. 27872474 3 43 theme fucose 327:332 arg1 levels 317:322 variable levels 308:322 variable levels of fucose, galactose, sialic acid, and bisecting N-acetylglucosamine (bisection) 308:403 This glycan consists of variable levels of fucose, galactose, sialic acid, and bisecting N-acetylglucosamine (bisection). 27872474 7 44 theme in 999:1000 arg1 sialylation 1008:1018 in vitro sialylation 999:1018 in vitro sialylation 999:1018 Decoy substrates were used to decrease the level of fucosylation or galactosylation, glycosyltransferases were transiently overexpressed to enhance bisection, galactosylation and sialylation and in vitro sialylation was applied for enhanced sialylation. 27872474 7 45 theme galactosylation 872:886 arg1 level 847:851 the level 843:851 the level of fucosylation or galactosylation 843:886 Decoy substrates were used to decrease the level of fucosylation or galactosylation, glycosyltransferases were transiently overexpressed to enhance bisection, galactosylation and sialylation and in vitro sialylation was applied for enhanced sialylation. 27872474 4 46 theme human 479:483 arg1 FcγRIII 485:491 the human FcγRIII 475:491 the human FcγRIII 475:491 Of these variations, the lack of fucose strongly enhances binding to the human FcγRIII, a finding which is currently used to improve the efficacy of therapeutic monoclonal antibodies. 27872474 4 46 theme human 479:483 arg1 finding 496:502 a finding 494:502 a finding which is currently used to improve the efficacy of therapeutic monoclonal antibodies 494:587 Of these variations, the lack of fucose strongly enhances binding to the human FcγRIII, a finding which is currently used to improve the efficacy of therapeutic monoclonal antibodies. 27872474 3 47 theme bisecting 363:371 arg1 bisection 394:402 bisection 394:402 bisection 394:402 This glycan consists of variable levels of fucose, galactose, sialic acid, and bisecting N-acetylglucosamine (bisection). 27872474 3 47 theme bisecting 363:371 arg1 N-acetylglucosamine 373:391 bisecting N-acetylglucosamine 363:391 bisecting N-acetylglucosamine (bisection) 363:403 This glycan consists of variable levels of fucose, galactose, sialic acid, and bisecting N-acetylglucosamine (bisection). 27872474 2 48 link N-linked 231:238 arg1 glycan 240:245 an evolutionary conserved N-linked glycan 205:245 an evolutionary conserved N-linked glycan 205:245 IgG contains an evolutionary conserved N-linked glycan at position Asn297 in the Fc-domain. 24640943 0 0 theme unprecedented 92:104 arg1 member 106:111 an unprecedented member 89:111 an unprecedented member of the cis-isoprenyl diphosphate synthase superfamily 89:165 Cyclolavandulyl skeleton biosynthesis via both condensation and cyclization catalyzed by an unprecedented member of the cis-isoprenyl diphosphate synthase superfamily. 24640943 5 1 theme homology 559:566 arg1 searches 568:575 homology searches 559:575 homology searches 559:575 Sequencing and homology searches identified one candidate gene product that consists of only a cis-isoprenyl diphosphate synthase domain. 24640943 7 2 theme monoterpene 1042:1052 arg1 structure 1054:1062 the cyclolavandulyl monoterpene structure 1022:1062 the cyclolavandulyl monoterpene structure 1022:1062 This enzyme is an unprecedented terpene synthase that catalyzes both the condensation of the C5 isoprene units and subsequent cyclization to form the cyclolavandulyl monoterpene structure. 24640943 4 3 theme cyclolavandulyl 517:531 arg1 structure 533:541 an N-linked cyclolavandulyl structure 505:541 an N-linked cyclolavandulyl structure 505:541 CL190, which produces lavanducyanin, a phenazine with an N-linked cyclolavandulyl structure. 24640943 0 4 theme cis-isoprenyl 120:132 arg1 superfamily 155:165 the cis-isoprenyl diphosphate synthase superfamily 116:165 the cis-isoprenyl diphosphate synthase superfamily 116:165 Cyclolavandulyl skeleton biosynthesis via both condensation and cyclization catalyzed by an unprecedented member of the cis-isoprenyl diphosphate synthase superfamily. 24640943 5 5 theme diphosphate 653:663 arg1 synthase 665:672 only a cis-isoprenyl diphosphate synthase 632:672 only a cis-isoprenyl diphosphate synthase domain 632:679 Sequencing and homology searches identified one candidate gene product that consists of only a cis-isoprenyl diphosphate synthase domain. 24640943 5 6 theme cis-isoprenyl 639:651 arg1 synthase 665:672 only a cis-isoprenyl diphosphate synthase 632:672 only a cis-isoprenyl diphosphate synthase domain 632:679 Sequencing and homology searches identified one candidate gene product that consists of only a cis-isoprenyl diphosphate synthase domain. 24640943 6 7 theme enzyme 749:754 arg1 analysis 721:728 biochemical analysis 709:728 biochemical analysis of the recombinant enzyme 709:754 Disruption of the gene and biochemical analysis of the recombinant enzyme demonstrated that the enzyme synthesized a cyclolavandulyl diphosphate essential for the biosynthesis of lavanducyanin. 24640943 6 7 theme enzyme 749:754 arg1 Disruption 682:691 Disruption 682:691 Disruption of the gene 682:703 Disruption of the gene and biochemical analysis of the recombinant enzyme demonstrated that the enzyme synthesized a cyclolavandulyl diphosphate essential for the biosynthesis of lavanducyanin. 24640943 3 8 theme biosynthesis 363:374 arg1 mechanism 376:384 the biosynthesis mechanism 359:384 the biosynthesis mechanism of this monoterpene 359:404 To determine the biosynthesis mechanism of this monoterpene, we sequenced the genome of Streptomyces sp. 24640943 5 9 theme synthase 665:672 arg1 domain 674:679 only a cis-isoprenyl diphosphate synthase domain 632:679 only a cis-isoprenyl diphosphate synthase domain 632:679 Sequencing and homology searches identified one candidate gene product that consists of only a cis-isoprenyl diphosphate synthase domain. 24640943 5 10 theme gene 602:605 arg1 product 607:613 one candidate gene product 588:613 one candidate gene product that consists of only a cis-isoprenyl diphosphate synthase domain 588:679 Sequencing and homology searches identified one candidate gene product that consists of only a cis-isoprenyl diphosphate synthase domain. 24640943 6 11 theme recombinant 737:747 arg1 enzyme 749:754 the recombinant enzyme 733:754 the recombinant enzyme 733:754 Disruption of the gene and biochemical analysis of the recombinant enzyme demonstrated that the enzyme synthesized a cyclolavandulyl diphosphate essential for the biosynthesis of lavanducyanin. 24640943 1 12 theme C10 197:199 arg1 monoterpene 201:211 a C10 monoterpene 195:211 a C10 monoterpene with a branched and cyclized carbon skeleton 195:256 A cyclolavandulyl group is a C10 monoterpene with a branched and cyclized carbon skeleton. 24640943 1 12 theme C10 197:199 arg1 group 186:190 A cyclolavandulyl group 168:190 A cyclolavandulyl group 168:190 A cyclolavandulyl group is a C10 monoterpene with a branched and cyclized carbon skeleton. 24640943 0 13 theme skeleton 16:23 arg1 biosynthesis 25:36 Cyclolavandulyl skeleton biosynthesis 0:36 Cyclolavandulyl skeleton biosynthesis via both condensation and cyclization 0:74 Cyclolavandulyl skeleton biosynthesis via both condensation and cyclization catalyzed by an unprecedented member of the cis-isoprenyl diphosphate synthase superfamily. 24640943 3 14 theme Streptomyces 434:445 arg1 sp 447:448 Streptomyces sp 434:448 Streptomyces sp 434:448 To determine the biosynthesis mechanism of this monoterpene, we sequenced the genome of Streptomyces sp. 24640943 0 15 theme Cyclolavandulyl 0:14 arg1 biosynthesis 25:36 Cyclolavandulyl skeleton biosynthesis 0:36 Cyclolavandulyl skeleton biosynthesis via both condensation and cyclization 0:74 Cyclolavandulyl skeleton biosynthesis via both condensation and cyclization catalyzed by an unprecedented member of the cis-isoprenyl diphosphate synthase superfamily. 24640943 7 16 theme subsequent 991:1000 arg1 cyclization 1002:1012 subsequent cyclization 991:1012 subsequent cyclization 991:1012 This enzyme is an unprecedented terpene synthase that catalyzes both the condensation of the C5 isoprene units and subsequent cyclization to form the cyclolavandulyl monoterpene structure. 24640943 7 17 theme unprecedented 894:906 arg1 synthase 916:923 an unprecedented terpene synthase 891:923 an unprecedented terpene synthase that catalyzes both the condensation of the C5 isoprene units and subsequent cyclization to form the cyclolavandulyl monoterpene structure 891:1062 This enzyme is an unprecedented terpene synthase that catalyzes both the condensation of the C5 isoprene units and subsequent cyclization to form the cyclolavandulyl monoterpene structure. 24640943 7 17 theme unprecedented 894:906 arg1 enzyme 881:886 This enzyme 876:886 This enzyme 876:886 This enzyme is an unprecedented terpene synthase that catalyzes both the condensation of the C5 isoprene units and subsequent cyclization to form the cyclolavandulyl monoterpene structure. 24640943 3 18 theme sp 447:448 arg1 genome 424:429 the genome 420:429 the genome of Streptomyces sp 420:448 To determine the biosynthesis mechanism of this monoterpene, we sequenced the genome of Streptomyces sp. 24640943 0 19 theme synthase 146:153 arg1 superfamily 155:165 the cis-isoprenyl diphosphate synthase superfamily 116:165 the cis-isoprenyl diphosphate synthase superfamily 116:165 Cyclolavandulyl skeleton biosynthesis via both condensation and cyclization catalyzed by an unprecedented member of the cis-isoprenyl diphosphate synthase superfamily. 24640943 6 20 theme lavanducyanin 861:873 arg1 biosynthesis 845:856 the biosynthesis 841:856 the biosynthesis of lavanducyanin 841:873 Disruption of the gene and biochemical analysis of the recombinant enzyme demonstrated that the enzyme synthesized a cyclolavandulyl diphosphate essential for the biosynthesis of lavanducyanin. 24640943 7 21 theme terpene 908:914 arg1 synthase 916:923 an unprecedented terpene synthase 891:923 an unprecedented terpene synthase that catalyzes both the condensation of the C5 isoprene units and subsequent cyclization to form the cyclolavandulyl monoterpene structure 891:1062 This enzyme is an unprecedented terpene synthase that catalyzes both the condensation of the C5 isoprene units and subsequent cyclization to form the cyclolavandulyl monoterpene structure. 24640943 7 21 theme terpene 908:914 arg1 enzyme 881:886 This enzyme 876:886 This enzyme 876:886 This enzyme is an unprecedented terpene synthase that catalyzes both the condensation of the C5 isoprene units and subsequent cyclization to form the cyclolavandulyl monoterpene structure. 24640943 3 22 theme monoterpene 394:404 arg1 mechanism 376:384 the biosynthesis mechanism 359:384 the biosynthesis mechanism of this monoterpene 359:404 To determine the biosynthesis mechanism of this monoterpene, we sequenced the genome of Streptomyces sp. 24640943 4 23 link N-linked 508:515 arg1 structure 533:541 an N-linked cyclolavandulyl structure 505:541 an N-linked cyclolavandulyl structure 505:541 CL190, which produces lavanducyanin, a phenazine with an N-linked cyclolavandulyl structure. 24640943 0 24 theme diphosphate 134:144 arg1 superfamily 155:165 the cis-isoprenyl diphosphate synthase superfamily 116:165 the cis-isoprenyl diphosphate synthase superfamily 116:165 Cyclolavandulyl skeleton biosynthesis via both condensation and cyclization catalyzed by an unprecedented member of the cis-isoprenyl diphosphate synthase superfamily. 24640943 6 25 theme biochemical 709:719 arg1 analysis 721:728 biochemical analysis 709:728 biochemical analysis of the recombinant enzyme 709:754 Disruption of the gene and biochemical analysis of the recombinant enzyme demonstrated that the enzyme synthesized a cyclolavandulyl diphosphate essential for the biosynthesis of lavanducyanin. 24640943 1 26 theme branched 220:227 arg1 skeleton 249:256 a branched and cyclized carbon skeleton 218:256 a branched and cyclized carbon skeleton 218:256 A cyclolavandulyl group is a C10 monoterpene with a branched and cyclized carbon skeleton. 24640943 7 27 theme cyclolavandulyl 1026:1040 arg1 structure 1054:1062 the cyclolavandulyl monoterpene structure 1022:1062 the cyclolavandulyl monoterpene structure 1022:1062 This enzyme is an unprecedented terpene synthase that catalyzes both the condensation of the C5 isoprene units and subsequent cyclization to form the cyclolavandulyl monoterpene structure. 24640943 7 28 theme units 981:985 arg1 condensation 949:960 the condensation 945:960 the condensation of the C5 isoprene units 945:985 This enzyme is an unprecedented terpene synthase that catalyzes both the condensation of the C5 isoprene units and subsequent cyclization to form the cyclolavandulyl monoterpene structure. 24640943 7 28 theme units 981:985 arg1 cyclization 1002:1012 subsequent cyclization 991:1012 subsequent cyclization 991:1012 This enzyme is an unprecedented terpene synthase that catalyzes both the condensation of the C5 isoprene units and subsequent cyclization to form the cyclolavandulyl monoterpene structure. 24640943 0 29 theme superfamily 155:165 arg1 member 106:111 an unprecedented member 89:111 an unprecedented member of the cis-isoprenyl diphosphate synthase superfamily 89:165 Cyclolavandulyl skeleton biosynthesis via both condensation and cyclization catalyzed by an unprecedented member of the cis-isoprenyl diphosphate synthase superfamily. 24640943 6 30 theme essential 827:835 arg1 diphosphate 815:825 a cyclolavandulyl diphosphate 797:825 a cyclolavandulyl diphosphate essential for the biosynthesis of lavanducyanin 797:873 Disruption of the gene and biochemical analysis of the recombinant enzyme demonstrated that the enzyme synthesized a cyclolavandulyl diphosphate essential for the biosynthesis of lavanducyanin. 24640943 1 31 theme cyclized 233:240 arg1 skeleton 249:256 a branched and cyclized carbon skeleton 218:256 a branched and cyclized carbon skeleton 218:256 A cyclolavandulyl group is a C10 monoterpene with a branched and cyclized carbon skeleton. 24640943 1 32 with monoterpene 201:211 arg1 skeleton 249:256 a branched and cyclized carbon skeleton 218:256 a branched and cyclized carbon skeleton 218:256 A cyclolavandulyl group is a C10 monoterpene with a branched and cyclized carbon skeleton. 24640943 6 33 theme cyclolavandulyl 799:813 arg1 diphosphate 815:825 a cyclolavandulyl diphosphate 797:825 a cyclolavandulyl diphosphate essential for the biosynthesis of lavanducyanin 797:873 Disruption of the gene and biochemical analysis of the recombinant enzyme demonstrated that the enzyme synthesized a cyclolavandulyl diphosphate essential for the biosynthesis of lavanducyanin. 24640943 6 34 theme gene 700:703 arg1 analysis 721:728 biochemical analysis 709:728 biochemical analysis of the recombinant enzyme 709:754 Disruption of the gene and biochemical analysis of the recombinant enzyme demonstrated that the enzyme synthesized a cyclolavandulyl diphosphate essential for the biosynthesis of lavanducyanin. 24640943 6 34 theme gene 700:703 arg1 Disruption 682:691 Disruption 682:691 Disruption of the gene 682:703 Disruption of the gene and biochemical analysis of the recombinant enzyme demonstrated that the enzyme synthesized a cyclolavandulyl diphosphate essential for the biosynthesis of lavanducyanin. 24640943 5 35 theme candidate 592:600 arg1 product 607:613 one candidate gene product 588:613 one candidate gene product that consists of only a cis-isoprenyl diphosphate synthase domain 588:679 Sequencing and homology searches identified one candidate gene product that consists of only a cis-isoprenyl diphosphate synthase domain. 24640943 1 36 theme carbon 242:247 arg1 skeleton 249:256 a branched and cyclized carbon skeleton 218:256 a branched and cyclized carbon skeleton 218:256 A cyclolavandulyl group is a C10 monoterpene with a branched and cyclized carbon skeleton. 24640943 1 37 theme cyclolavandulyl 170:184 arg1 monoterpene 201:211 a C10 monoterpene 195:211 a C10 monoterpene with a branched and cyclized carbon skeleton 195:256 A cyclolavandulyl group is a C10 monoterpene with a branched and cyclized carbon skeleton. 24640943 1 37 theme cyclolavandulyl 170:184 arg1 group 186:190 A cyclolavandulyl group 168:190 A cyclolavandulyl group 168:190 A cyclolavandulyl group is a C10 monoterpene with a branched and cyclized carbon skeleton. 24640943 7 38 theme C5 969:970 arg1 units 981:985 the C5 isoprene units 965:985 the C5 isoprene units 965:985 This enzyme is an unprecedented terpene synthase that catalyzes both the condensation of the C5 isoprene units and subsequent cyclization to form the cyclolavandulyl monoterpene structure. 24640943 2 39 located found 286:290 arg1 nature 295:300 nature 295:300 nature 295:300 This monoterpene is rarely found in nature, and its biosynthesis is poorly understood. 24640943 2 39 located found 286:290 arg2 monoterpene 264:274 This monoterpene 259:274 This monoterpene 259:274 This monoterpene is rarely found in nature, and its biosynthesis is poorly understood. 24640943 7 40 theme isoprene 972:979 arg1 units 981:985 the C5 isoprene units 965:985 the C5 isoprene units 965:985 This enzyme is an unprecedented terpene synthase that catalyzes both the condensation of the C5 isoprene units and subsequent cyclization to form the cyclolavandulyl monoterpene structure. 24640943 4 41 theme N-linked 508:515 arg1 structure 533:541 an N-linked cyclolavandulyl structure 505:541 an N-linked cyclolavandulyl structure 505:541 CL190, which produces lavanducyanin, a phenazine with an N-linked cyclolavandulyl structure. 24640943 4 42 with phenazine 490:498 arg1 structure 533:541 an N-linked cyclolavandulyl structure 505:541 an N-linked cyclolavandulyl structure 505:541 CL190, which produces lavanducyanin, a phenazine with an N-linked cyclolavandulyl structure. 25951442 3 0 theme components 522:531 arg1 identification 494:507 the identification 490:507 the identification of essential components of a cellular machine 490:553 One approach for the identification of essential components of a cellular machine involves the determination of its minimal protein composition. 25951442 8 1 theme PG 1669:1670 arg1 enzymes 1685:1691 only two active PG synthesizing enzymes 1653:1691 only two active PG synthesizing enzymes 1653:1691 The fact that S. aureus can grow and divide with only two active PG synthesizing enzymes shows that most of these enzymes are redundant in vitro and identifies the minimal PG synthesis machinery of S. aureus. 25951442 6 2 from genome 1048:1053 arg1 enzymes 1021:1027 PG synthesis enzymes 1008:1027 PG synthesis enzymes from the S. aureus genome 1008:1053 We deleted seven of the nine genes encoding PG synthesis enzymes from the S. aureus genome without affecting normal growth or cell morphology, generating a strain capable of PG biosynthesis catalyzed only by two penicillin-binding proteins, PBP1 and the bi-functional PBP2. 25951442 2 3 theme bacterial 307:315 arg1 PG 332:333 PG 332:333 PG 332:333 An example is the bacterial peptidoglycan (PG) synthesis machine, responsible for the synthesis of the main component of the cell wall and the target of many contemporary antibiotics. 25951442 2 3 theme bacterial 307:315 arg1 peptidoglycan 317:329 bacterial peptidoglycan 307:329 the bacterial peptidoglycan (PG) synthesis machine 303:352 An example is the bacterial peptidoglycan (PG) synthesis machine, responsible for the synthesis of the main component of the cell wall and the target of many contemporary antibiotics. 25951442 1 4 theme Many 130:133 arg1 processes 154:162 Many important cellular processes 130:162 Many important cellular processes 130:162 Many important cellular processes are performed by molecular machines, composed of multiple proteins that physically interact to execute biological functions. 25951442 7 5 theme wall-targeting 1396:1409 arg1 antibiotics 1411:1421 cell wall-targeting antibiotics 1391:1421 cell wall-targeting antibiotics 1391:1421 However, multiple PBPs are important in clinically relevant environments, as bacteria with a minimal PG synthesis machinery became highly susceptible to cell wall-targeting antibiotics, host lytic enzymes and displayed impaired virulence in a Drosophila infection model which is dependent on the presence of specific peptidoglycan receptor proteins, namely PGRP-SA. 25951442 7 5 theme wall-targeting 1396:1409 arg1 enzymes 1435:1441 host lytic enzymes 1424:1441 host lytic enzymes 1424:1441 However, multiple PBPs are important in clinically relevant environments, as bacteria with a minimal PG synthesis machinery became highly susceptible to cell wall-targeting antibiotics, host lytic enzymes and displayed impaired virulence in a Drosophila infection model which is dependent on the presence of specific peptidoglycan receptor proteins, namely PGRP-SA. 25951442 7 6 theme relevant 1289:1296 arg1 environments 1298:1309 clinically relevant environments 1278:1309 clinically relevant environments 1278:1309 However, multiple PBPs are important in clinically relevant environments, as bacteria with a minimal PG synthesis machinery became highly susceptible to cell wall-targeting antibiotics, host lytic enzymes and displayed impaired virulence in a Drosophila infection model which is dependent on the presence of specific peptidoglycan receptor proteins, namely PGRP-SA. 25951442 3 7 theme machine 547:553 arg1 components 522:531 essential components 512:531 essential components of a cellular machine 512:553 One approach for the identification of essential components of a cellular machine involves the determination of its minimal protein composition. 25951442 5 8 theme model 868:872 arg1 organisms 874:882 other model organisms 862:882 other model organisms 862:882 Its genome encodes a low number of proteins with PG synthesis activity (9 proteins), when compared to other model organisms, and is therefore a good model for the study of a minimal PG synthesis machine. 25951442 6 9 theme capable 1127:1133 arg1 strain 1120:1125 a strain 1118:1125 a strain capable of PG biosynthesis catalyzed only by two penicillin-binding proteins, PBP1 and the bi-functional PBP2 1118:1235 We deleted seven of the nine genes encoding PG synthesis enzymes from the S. aureus genome without affecting normal growth or cell morphology, generating a strain capable of PG biosynthesis catalyzed only by two penicillin-binding proteins, PBP1 and the bi-functional PBP2. 25951442 4 10 theme many 700:703 arg1 antibiotics 719:729 many commonly used antibiotics 700:729 many commonly used antibiotics 700:729 Staphylococcus aureus is a Gram-positive pathogen, renowned for its resistance to many commonly used antibiotics and prevalence in hospitals. 25951442 3 11 theme minimal 589:595 arg1 composition 605:615 its minimal protein composition 585:615 its minimal protein composition 585:615 One approach for the identification of essential components of a cellular machine involves the determination of its minimal protein composition. 25951442 9 12 theme expendable 1912:1921 arg1 enzymes 1936:1942 the expendable PG synthesis enzymes 1908:1942 the expendable PG synthesis enzymes 1908:1942 However a complex molecular machine is important in environments other than in vitro growth as the expendable PG synthesis enzymes play an important role in the pathogenicity and antibiotic resistance of S. aureus. 25951442 9 13 dep in 1889:1890 arg1 vitro 1892:1896 vitro 1892:1896 vitro 1892:1896 However a complex molecular machine is important in environments other than in vitro growth as the expendable PG synthesis enzymes play an important role in the pathogenicity and antibiotic resistance of S. aureus. 25951442 7 14 theme PG 1339:1340 arg1 machinery 1352:1360 a minimal PG synthesis machinery 1329:1360 a minimal PG synthesis machinery 1329:1360 However, multiple PBPs are important in clinically relevant environments, as bacteria with a minimal PG synthesis machinery became highly susceptible to cell wall-targeting antibiotics, host lytic enzymes and displayed impaired virulence in a Drosophila infection model which is dependent on the presence of specific peptidoglycan receptor proteins, namely PGRP-SA. 25951442 9 15 theme synthesis 1926:1934 arg1 enzymes 1936:1942 the expendable PG synthesis enzymes 1908:1942 the expendable PG synthesis enzymes 1908:1942 However a complex molecular machine is important in environments other than in vitro growth as the expendable PG synthesis enzymes play an important role in the pathogenicity and antibiotic resistance of S. aureus. 25951442 3 16 theme composition 605:615 arg1 determination 568:580 the determination 564:580 the determination of its minimal protein composition 564:615 One approach for the identification of essential components of a cellular machine involves the determination of its minimal protein composition. 25951442 1 17 theme important 135:143 arg1 processes 154:162 Many important cellular processes 130:162 Many important cellular processes 130:162 Many important cellular processes are performed by molecular machines, composed of multiple proteins that physically interact to execute biological functions. 25951442 6 18 theme penicillin-binding 1176:1193 arg1 PBP2 1232:1235 the bi-functional PBP2 1214:1235 the bi-functional PBP2 1214:1235 We deleted seven of the nine genes encoding PG synthesis enzymes from the S. aureus genome without affecting normal growth or cell morphology, generating a strain capable of PG biosynthesis catalyzed only by two penicillin-binding proteins, PBP1 and the bi-functional PBP2. 25951442 6 18 theme penicillin-binding 1176:1193 arg1 PBP1 1205:1208 PBP1 1205:1208 PBP1 1205:1208 We deleted seven of the nine genes encoding PG synthesis enzymes from the S. aureus genome without affecting normal growth or cell morphology, generating a strain capable of PG biosynthesis catalyzed only by two penicillin-binding proteins, PBP1 and the bi-functional PBP2. 25951442 6 18 theme penicillin-binding 1176:1193 arg1 proteins 1195:1202 two penicillin-binding proteins 1172:1202 two penicillin-binding proteins 1172:1202 We deleted seven of the nine genes encoding PG synthesis enzymes from the S. aureus genome without affecting normal growth or cell morphology, generating a strain capable of PG biosynthesis catalyzed only by two penicillin-binding proteins, PBP1 and the bi-functional PBP2. 25951442 6 19 theme genes 993:997 arg1 seven 975:979 seven 975:979 seven 975:979 We deleted seven of the nine genes encoding PG synthesis enzymes from the S. aureus genome without affecting normal growth or cell morphology, generating a strain capable of PG biosynthesis catalyzed only by two penicillin-binding proteins, PBP1 and the bi-functional PBP2. 25951442 6 19 theme genes 993:997 arg1 genes 993:997 the nine genes 984:997 the nine genes encoding PG synthesis enzymes from the S. aureus genome 984:1053 We deleted seven of the nine genes encoding PG synthesis enzymes from the S. aureus genome without affecting normal growth or cell morphology, generating a strain capable of PG biosynthesis catalyzed only by two penicillin-binding proteins, PBP1 and the bi-functional PBP2. 25951442 9 20 theme important 1952:1960 arg1 role 1962:1965 an important role 1949:1965 an important role 1949:1965 However a complex molecular machine is important in environments other than in vitro growth as the expendable PG synthesis enzymes play an important role in the pathogenicity and antibiotic resistance of S. aureus. 25951442 4 21 theme used 714:717 arg1 antibiotics 719:729 many commonly used antibiotics 700:729 many commonly used antibiotics 700:729 Staphylococcus aureus is a Gram-positive pathogen, renowned for its resistance to many commonly used antibiotics and prevalence in hospitals. 25951442 8 22 theme minimal 1768:1774 arg1 machinery 1789:1797 the minimal PG synthesis machinery 1764:1797 the minimal PG synthesis machinery of S. aureus 1764:1810 The fact that S. aureus can grow and divide with only two active PG synthesizing enzymes shows that most of these enzymes are redundant in vitro and identifies the minimal PG synthesis machinery of S. aureus. 25951442 7 23 theme proteins 1578:1585 arg1 presence 1534:1541 the presence 1530:1541 the presence of specific peptidoglycan receptor proteins, namely PGRP-SA 1530:1601 However, multiple PBPs are important in clinically relevant environments, as bacteria with a minimal PG synthesis machinery became highly susceptible to cell wall-targeting antibiotics, host lytic enzymes and displayed impaired virulence in a Drosophila infection model which is dependent on the presence of specific peptidoglycan receptor proteins, namely PGRP-SA. 25951442 5 24 theme proteins 795:802 arg1 number 785:790 a low number 779:790 a low number of proteins with PG synthesis activity (9 proteins) 779:842 Its genome encodes a low number of proteins with PG synthesis activity (9 proteins), when compared to other model organisms, and is therefore a good model for the study of a minimal PG synthesis machine. 25951442 5 24 theme proteins 795:802 arg1 genome 764:769 Its genome 760:769 Its genome 760:769 Its genome encodes a low number of proteins with PG synthesis activity (9 proteins), when compared to other model organisms, and is therefore a good model for the study of a minimal PG synthesis machine. 25951442 8 25 theme synthesis 1779:1787 arg1 machinery 1789:1797 the minimal PG synthesis machinery 1764:1797 the minimal PG synthesis machinery of S. aureus 1764:1810 The fact that S. aureus can grow and divide with only two active PG synthesizing enzymes shows that most of these enzymes are redundant in vitro and identifies the minimal PG synthesis machinery of S. aureus. 25951442 1 26 theme molecular 181:189 arg1 machines 191:198 molecular machines 181:198 molecular machines 181:198 Many important cellular processes are performed by molecular machines, composed of multiple proteins that physically interact to execute biological functions. 25951442 7 27 theme peptidoglycan 1555:1567 arg1 proteins 1578:1585 specific peptidoglycan receptor proteins 1546:1585 specific peptidoglycan receptor proteins 1546:1585 However, multiple PBPs are important in clinically relevant environments, as bacteria with a minimal PG synthesis machinery became highly susceptible to cell wall-targeting antibiotics, host lytic enzymes and displayed impaired virulence in a Drosophila infection model which is dependent on the presence of specific peptidoglycan receptor proteins, namely PGRP-SA. 25951442 7 27 theme peptidoglycan 1555:1567 arg1 PGRP-SA 1595:1601 PGRP-SA 1595:1601 PGRP-SA 1595:1601 However, multiple PBPs are important in clinically relevant environments, as bacteria with a minimal PG synthesis machinery became highly susceptible to cell wall-targeting antibiotics, host lytic enzymes and displayed impaired virulence in a Drosophila infection model which is dependent on the presence of specific peptidoglycan receptor proteins, namely PGRP-SA. 25951442 7 28 theme minimal 1331:1337 arg1 machinery 1352:1360 a minimal PG synthesis machinery 1329:1360 a minimal PG synthesis machinery 1329:1360 However, multiple PBPs are important in clinically relevant environments, as bacteria with a minimal PG synthesis machinery became highly susceptible to cell wall-targeting antibiotics, host lytic enzymes and displayed impaired virulence in a Drosophila infection model which is dependent on the presence of specific peptidoglycan receptor proteins, namely PGRP-SA. 25951442 6 29 theme biosynthesis 1141:1152 arg1 capable 1127:1133 capable 1127:1133 capable 1127:1133 We deleted seven of the nine genes encoding PG synthesis enzymes from the S. aureus genome without affecting normal growth or cell morphology, generating a strain capable of PG biosynthesis catalyzed only by two penicillin-binding proteins, PBP1 and the bi-functional PBP2. 25951442 5 30 theme synthesis 945:953 arg1 machine 955:961 a minimal PG synthesis machine 932:961 a minimal PG synthesis machine 932:961 Its genome encodes a low number of proteins with PG synthesis activity (9 proteins), when compared to other model organisms, and is therefore a good model for the study of a minimal PG synthesis machine. 25951442 9 31 theme antibiotic 1992:2001 arg1 resistance 2003:2012 antibiotic resistance 1992:2012 antibiotic resistance 1992:2012 However a complex molecular machine is important in environments other than in vitro growth as the expendable PG synthesis enzymes play an important role in the pathogenicity and antibiotic resistance of S. aureus. 25951442 8 32 theme aureus 1805:1810 arg1 machinery 1789:1797 the minimal PG synthesis machinery 1764:1797 the minimal PG synthesis machinery of S. aureus 1764:1810 The fact that S. aureus can grow and divide with only two active PG synthesizing enzymes shows that most of these enzymes are redundant in vitro and identifies the minimal PG synthesis machinery of S. aureus. 25951442 6 33 theme aureus 1041:1046 arg1 genome 1048:1053 the S. aureus genome 1034:1053 the S. aureus genome 1034:1053 We deleted seven of the nine genes encoding PG synthesis enzymes from the S. aureus genome without affecting normal growth or cell morphology, generating a strain capable of PG biosynthesis catalyzed only by two penicillin-binding proteins, PBP1 and the bi-functional PBP2. 25951442 2 34 theme contemporary 447:458 arg1 antibiotics 460:470 many contemporary antibiotics 442:470 many contemporary antibiotics 442:470 An example is the bacterial peptidoglycan (PG) synthesis machine, responsible for the synthesis of the main component of the cell wall and the target of many contemporary antibiotics. 25951442 5 35 theme low 781:783 arg1 number 785:790 a low number 779:790 a low number of proteins with PG synthesis activity (9 proteins) 779:842 Its genome encodes a low number of proteins with PG synthesis activity (9 proteins), when compared to other model organisms, and is therefore a good model for the study of a minimal PG synthesis machine. 25951442 5 35 theme low 781:783 arg1 genome 764:769 Its genome 760:769 Its genome 760:769 Its genome encodes a low number of proteins with PG synthesis activity (9 proteins), when compared to other model organisms, and is therefore a good model for the study of a minimal PG synthesis machine. 25951442 2 36 theme component 397:405 arg1 synthesis 375:383 the synthesis 371:383 the synthesis of the main component of the cell wall and the target of many contemporary antibiotics 371:470 An example is the bacterial peptidoglycan (PG) synthesis machine, responsible for the synthesis of the main component of the cell wall and the target of many contemporary antibiotics. 25951442 0 37 dep Sacrifices 82:91 arg1 Sacrifices 82:91 Sacrifices Virulence and Antibiotic Resistance 82:127 Sacrifices Virulence and Antibiotic Resistance 82:127 Staphylococcus aureus Survives with a Minimal Peptidoglycan Synthesis Machine but Sacrifices Virulence and Antibiotic Resistance. 25951442 0 37 dep Sacrifices 82:91 arg1 Virulence 93:101 Virulence 93:101 Virulence 93:101 Staphylococcus aureus Survives with a Minimal Peptidoglycan Synthesis Machine but Sacrifices Virulence and Antibiotic Resistance. 25951442 0 37 dep Sacrifices 82:91 arg1 Resistance 118:127 Antibiotic Resistance 107:127 Antibiotic Resistance 107:127 Staphylococcus aureus Survives with a Minimal Peptidoglycan Synthesis Machine but Sacrifices Virulence and Antibiotic Resistance. 25951442 9 38 theme aureus 2020:2025 arg1 pathogenicity 1974:1986 pathogenicity 1974:1986 pathogenicity 1974:1986 However a complex molecular machine is important in environments other than in vitro growth as the expendable PG synthesis enzymes play an important role in the pathogenicity and antibiotic resistance of S. aureus. 25951442 9 38 theme aureus 2020:2025 arg1 resistance 2003:2012 antibiotic resistance 1992:2012 antibiotic resistance 1992:2012 However a complex molecular machine is important in environments other than in vitro growth as the expendable PG synthesis enzymes play an important role in the pathogenicity and antibiotic resistance of S. aureus. 25951442 6 39 theme PG 1138:1139 arg1 biosynthesis 1141:1152 PG biosynthesis 1138:1152 PG biosynthesis catalyzed only by two penicillin-binding proteins, PBP1 and the bi-functional PBP2 1138:1235 We deleted seven of the nine genes encoding PG synthesis enzymes from the S. aureus genome without affecting normal growth or cell morphology, generating a strain capable of PG biosynthesis catalyzed only by two penicillin-binding proteins, PBP1 and the bi-functional PBP2. 25951442 5 40 theme minimal 934:940 arg1 machine 955:961 a minimal PG synthesis machine 932:961 a minimal PG synthesis machine 932:961 Its genome encodes a low number of proteins with PG synthesis activity (9 proteins), when compared to other model organisms, and is therefore a good model for the study of a minimal PG synthesis machine. 25951442 2 41 theme wall 419:422 arg1 target 432:437 the target 428:437 the target of many contemporary antibiotics 428:470 An example is the bacterial peptidoglycan (PG) synthesis machine, responsible for the synthesis of the main component of the cell wall and the target of many contemporary antibiotics. 25951442 2 41 theme wall 419:422 arg1 component 397:405 the main component 388:405 the main component of the cell wall 388:422 An example is the bacterial peptidoglycan (PG) synthesis machine, responsible for the synthesis of the main component of the cell wall and the target of many contemporary antibiotics. 25951442 5 42 theme PG 809:810 arg1 activity 822:829 PG synthesis activity 809:829 PG synthesis activity 809:829 Its genome encodes a low number of proteins with PG synthesis activity (9 proteins), when compared to other model organisms, and is therefore a good model for the study of a minimal PG synthesis machine. 25951442 6 43 theme PG 1008:1009 arg1 enzymes 1021:1027 PG synthesis enzymes 1008:1027 PG synthesis enzymes from the S. aureus genome 1008:1053 We deleted seven of the nine genes encoding PG synthesis enzymes from the S. aureus genome without affecting normal growth or cell morphology, generating a strain capable of PG biosynthesis catalyzed only by two penicillin-binding proteins, PBP1 and the bi-functional PBP2. 25951442 0 44 theme Peptidoglycan 46:58 arg1 Machine 70:76 a Minimal Peptidoglycan Synthesis Machine 36:76 a Minimal Peptidoglycan Synthesis Machine 36:76 Staphylococcus aureus Survives with a Minimal Peptidoglycan Synthesis Machine but Sacrifices Virulence and Antibiotic Resistance. 25951442 9 45 dep growth 1898:1903 arg1 play 1944:1947 play 1944:1947 play an important role in the pathogenicity and antibiotic resistance of S. aureus 1944:2025 However a complex molecular machine is important in environments other than in vitro growth as the expendable PG synthesis enzymes play an important role in the pathogenicity and antibiotic resistance of S. aureus. 25951442 7 46 theme Drosophila 1481:1490 arg1 model 1502:1506 a Drosophila infection model 1479:1506 a Drosophila infection model which is dependent on the presence of specific peptidoglycan receptor proteins, namely PGRP-SA 1479:1601 However, multiple PBPs are important in clinically relevant environments, as bacteria with a minimal PG synthesis machinery became highly susceptible to cell wall-targeting antibiotics, host lytic enzymes and displayed impaired virulence in a Drosophila infection model which is dependent on the presence of specific peptidoglycan receptor proteins, namely PGRP-SA. 25951442 7 46 theme Drosophila 1481:1490 arg1 dependent 1517:1525 dependent 1517:1525 dependent 1517:1525 However, multiple PBPs are important in clinically relevant environments, as bacteria with a minimal PG synthesis machinery became highly susceptible to cell wall-targeting antibiotics, host lytic enzymes and displayed impaired virulence in a Drosophila infection model which is dependent on the presence of specific peptidoglycan receptor proteins, namely PGRP-SA. 25951442 9 47 theme molecular 1831:1839 arg1 important 1852:1860 important 1852:1860 important 1852:1860 However a complex molecular machine is important in environments other than in vitro growth as the expendable PG synthesis enzymes play an important role in the pathogenicity and antibiotic resistance of S. aureus. 25951442 9 47 theme molecular 1831:1839 arg1 machine 1841:1847 a complex molecular machine 1821:1847 a complex molecular machine 1821:1847 However a complex molecular machine is important in environments other than in vitro growth as the expendable PG synthesis enzymes play an important role in the pathogenicity and antibiotic resistance of S. aureus. 25951442 4 48 from prevalence 735:744 arg1 hospitals 749:757 hospitals 749:757 hospitals 749:757 Staphylococcus aureus is a Gram-positive pathogen, renowned for its resistance to many commonly used antibiotics and prevalence in hospitals. 25951442 5 49 theme synthesis 812:820 arg1 activity 822:829 PG synthesis activity 809:829 PG synthesis activity 809:829 Its genome encodes a low number of proteins with PG synthesis activity (9 proteins), when compared to other model organisms, and is therefore a good model for the study of a minimal PG synthesis machine. 25951442 6 50 theme normal 1073:1078 arg1 growth 1080:1085 normal growth 1073:1085 normal growth 1073:1085 We deleted seven of the nine genes encoding PG synthesis enzymes from the S. aureus genome without affecting normal growth or cell morphology, generating a strain capable of PG biosynthesis catalyzed only by two penicillin-binding proteins, PBP1 and the bi-functional PBP2. 25951442 3 51 theme essential 512:520 arg1 components 522:531 essential components 512:531 essential components of a cellular machine 512:553 One approach for the identification of essential components of a cellular machine involves the determination of its minimal protein composition. 25951442 4 52 from antibiotics 719:729 arg1 hospitals 749:757 hospitals 749:757 hospitals 749:757 Staphylococcus aureus is a Gram-positive pathogen, renowned for its resistance to many commonly used antibiotics and prevalence in hospitals. 25951442 7 53 theme impaired 1457:1464 arg1 virulence 1466:1474 impaired virulence 1457:1474 impaired virulence 1457:1474 However, multiple PBPs are important in clinically relevant environments, as bacteria with a minimal PG synthesis machinery became highly susceptible to cell wall-targeting antibiotics, host lytic enzymes and displayed impaired virulence in a Drosophila infection model which is dependent on the presence of specific peptidoglycan receptor proteins, namely PGRP-SA. 25951442 2 54 theme peptidoglycan 317:329 arg1 machine 346:352 the bacterial peptidoglycan (PG) synthesis machine 303:352 the bacterial peptidoglycan (PG) synthesis machine 303:352 An example is the bacterial peptidoglycan (PG) synthesis machine, responsible for the synthesis of the main component of the cell wall and the target of many contemporary antibiotics. 25951442 2 54 theme peptidoglycan 317:329 arg1 example 292:298 An example 289:298 An example 289:298 An example is the bacterial peptidoglycan (PG) synthesis machine, responsible for the synthesis of the main component of the cell wall and the target of many contemporary antibiotics. 25951442 8 55 theme active 1662:1667 arg1 enzymes 1685:1691 only two active PG synthesizing enzymes 1653:1691 only two active PG synthesizing enzymes 1653:1691 The fact that S. aureus can grow and divide with only two active PG synthesizing enzymes shows that most of these enzymes are redundant in vitro and identifies the minimal PG synthesis machinery of S. aureus. 25951442 7 56 theme host 1424:1427 arg1 antibiotics 1411:1421 cell wall-targeting antibiotics 1391:1421 cell wall-targeting antibiotics 1391:1421 However, multiple PBPs are important in clinically relevant environments, as bacteria with a minimal PG synthesis machinery became highly susceptible to cell wall-targeting antibiotics, host lytic enzymes and displayed impaired virulence in a Drosophila infection model which is dependent on the presence of specific peptidoglycan receptor proteins, namely PGRP-SA. 25951442 7 56 theme host 1424:1427 arg1 enzymes 1435:1441 host lytic enzymes 1424:1441 host lytic enzymes 1424:1441 However, multiple PBPs are important in clinically relevant environments, as bacteria with a minimal PG synthesis machinery became highly susceptible to cell wall-targeting antibiotics, host lytic enzymes and displayed impaired virulence in a Drosophila infection model which is dependent on the presence of specific peptidoglycan receptor proteins, namely PGRP-SA. 25951442 9 57 theme other 1878:1882 arg1 environments 1865:1876 environments 1865:1876 environments other than in vitro growth as the expendable PG synthesis enzymes play an important role in the pathogenicity and antibiotic resistance of S. aureus 1865:2025 However a complex molecular machine is important in environments other than in vitro growth as the expendable PG synthesis enzymes play an important role in the pathogenicity and antibiotic resistance of S. aureus. 25951442 3 58 theme cellular 538:545 arg1 machine 547:553 a cellular machine 536:553 a cellular machine 536:553 One approach for the identification of essential components of a cellular machine involves the determination of its minimal protein composition. 25951442 8 59 theme synthesizing 1672:1683 arg1 enzymes 1685:1691 only two active PG synthesizing enzymes 1653:1691 only two active PG synthesizing enzymes 1653:1691 The fact that S. aureus can grow and divide with only two active PG synthesizing enzymes shows that most of these enzymes are redundant in vitro and identifies the minimal PG synthesis machinery of S. aureus. 25951442 5 60 theme other 862:866 arg1 organisms 874:882 other model organisms 862:882 other model organisms 862:882 Its genome encodes a low number of proteins with PG synthesis activity (9 proteins), when compared to other model organisms, and is therefore a good model for the study of a minimal PG synthesis machine. 25951442 7 61 theme lytic 1429:1433 arg1 antibiotics 1411:1421 cell wall-targeting antibiotics 1391:1421 cell wall-targeting antibiotics 1391:1421 However, multiple PBPs are important in clinically relevant environments, as bacteria with a minimal PG synthesis machinery became highly susceptible to cell wall-targeting antibiotics, host lytic enzymes and displayed impaired virulence in a Drosophila infection model which is dependent on the presence of specific peptidoglycan receptor proteins, namely PGRP-SA. 25951442 7 61 theme lytic 1429:1433 arg1 enzymes 1435:1441 host lytic enzymes 1424:1441 host lytic enzymes 1424:1441 However, multiple PBPs are important in clinically relevant environments, as bacteria with a minimal PG synthesis machinery became highly susceptible to cell wall-targeting antibiotics, host lytic enzymes and displayed impaired virulence in a Drosophila infection model which is dependent on the presence of specific peptidoglycan receptor proteins, namely PGRP-SA. 25951442 9 62 from important 1852:1860 arg1 environments 1865:1876 environments 1865:1876 environments other than in vitro growth as the expendable PG synthesis enzymes play an important role in the pathogenicity and antibiotic resistance of S. aureus 1865:2025 However a complex molecular machine is important in environments other than in vitro growth as the expendable PG synthesis enzymes play an important role in the pathogenicity and antibiotic resistance of S. aureus. 25951442 9 63 theme in 1889:1890 arg1 growth 1898:1903 in vitro growth 1889:1903 in vitro growth as the expendable PG synthesis enzymes play an important role in the pathogenicity and antibiotic resistance of S. aureus 1889:2025 However a complex molecular machine is important in environments other than in vitro growth as the expendable PG synthesis enzymes play an important role in the pathogenicity and antibiotic resistance of S. aureus. 25951442 6 64 theme bi-functional 1218:1230 arg1 PBP2 1232:1235 the bi-functional PBP2 1214:1235 the bi-functional PBP2 1214:1235 We deleted seven of the nine genes encoding PG synthesis enzymes from the S. aureus genome without affecting normal growth or cell morphology, generating a strain capable of PG biosynthesis catalyzed only by two penicillin-binding proteins, PBP1 and the bi-functional PBP2. 25951442 6 64 theme bi-functional 1218:1230 arg1 proteins 1195:1202 two penicillin-binding proteins 1172:1202 two penicillin-binding proteins 1172:1202 We deleted seven of the nine genes encoding PG synthesis enzymes from the S. aureus genome without affecting normal growth or cell morphology, generating a strain capable of PG biosynthesis catalyzed only by two penicillin-binding proteins, PBP1 and the bi-functional PBP2. 25951442 2 65 theme synthesis 336:344 arg1 machine 346:352 the bacterial peptidoglycan (PG) synthesis machine 303:352 the bacterial peptidoglycan (PG) synthesis machine 303:352 An example is the bacterial peptidoglycan (PG) synthesis machine, responsible for the synthesis of the main component of the cell wall and the target of many contemporary antibiotics. 25951442 2 65 theme synthesis 336:344 arg1 example 292:298 An example 289:298 An example 289:298 An example is the bacterial peptidoglycan (PG) synthesis machine, responsible for the synthesis of the main component of the cell wall and the target of many contemporary antibiotics. 25951442 7 66 theme cell 1391:1394 arg1 antibiotics 1411:1421 cell wall-targeting antibiotics 1391:1421 cell wall-targeting antibiotics 1391:1421 However, multiple PBPs are important in clinically relevant environments, as bacteria with a minimal PG synthesis machinery became highly susceptible to cell wall-targeting antibiotics, host lytic enzymes and displayed impaired virulence in a Drosophila infection model which is dependent on the presence of specific peptidoglycan receptor proteins, namely PGRP-SA. 25951442 7 66 theme cell 1391:1394 arg1 enzymes 1435:1441 host lytic enzymes 1424:1441 host lytic enzymes 1424:1441 However, multiple PBPs are important in clinically relevant environments, as bacteria with a minimal PG synthesis machinery became highly susceptible to cell wall-targeting antibiotics, host lytic enzymes and displayed impaired virulence in a Drosophila infection model which is dependent on the presence of specific peptidoglycan receptor proteins, namely PGRP-SA. 25951442 1 67 theme multiple 213:220 arg1 proteins 222:229 multiple proteins 213:229 multiple proteins that physically interact to execute biological functions 213:286 Many important cellular processes are performed by molecular machines, composed of multiple proteins that physically interact to execute biological functions. 25951442 9 68 theme PG 1923:1924 arg1 enzymes 1936:1942 the expendable PG synthesis enzymes 1908:1942 the expendable PG synthesis enzymes 1908:1942 However a complex molecular machine is important in environments other than in vitro growth as the expendable PG synthesis enzymes play an important role in the pathogenicity and antibiotic resistance of S. aureus. 25951442 3 69 theme protein 597:603 arg1 composition 605:615 its minimal protein composition 585:615 its minimal protein composition 585:615 One approach for the identification of essential components of a cellular machine involves the determination of its minimal protein composition. 25951442 5 70 theme good 904:907 arg1 model 909:913 a good model 902:913 a good model for the study of a minimal PG synthesis machine 902:961 Its genome encodes a low number of proteins with PG synthesis activity (9 proteins), when compared to other model organisms, and is therefore a good model for the study of a minimal PG synthesis machine. 25951442 7 71 theme synthesis 1342:1350 arg1 machinery 1352:1360 a minimal PG synthesis machinery 1329:1360 a minimal PG synthesis machinery 1329:1360 However, multiple PBPs are important in clinically relevant environments, as bacteria with a minimal PG synthesis machinery became highly susceptible to cell wall-targeting antibiotics, host lytic enzymes and displayed impaired virulence in a Drosophila infection model which is dependent on the presence of specific peptidoglycan receptor proteins, namely PGRP-SA. 25951442 1 72 theme cellular 145:152 arg1 processes 154:162 Many important cellular processes 130:162 Many important cellular processes 130:162 Many important cellular processes are performed by molecular machines, composed of multiple proteins that physically interact to execute biological functions. 25951442 9 73 from environments 1865:1876 arg1 important 1852:1860 important 1852:1860 important 1852:1860 However a complex molecular machine is important in environments other than in vitro growth as the expendable PG synthesis enzymes play an important role in the pathogenicity and antibiotic resistance of S. aureus. 25951442 9 73 from environments 1865:1876 arg1 machine 1841:1847 a complex molecular machine 1821:1847 a complex molecular machine 1821:1847 However a complex molecular machine is important in environments other than in vitro growth as the expendable PG synthesis enzymes play an important role in the pathogenicity and antibiotic resistance of S. aureus. 25951442 5 74 with proteins 795:802 arg1 activity 822:829 PG synthesis activity 809:829 PG synthesis activity 809:829 Its genome encodes a low number of proteins with PG synthesis activity (9 proteins), when compared to other model organisms, and is therefore a good model for the study of a minimal PG synthesis machine. 25951442 7 75 with bacteria 1315:1322 arg1 machinery 1352:1360 a minimal PG synthesis machinery 1329:1360 a minimal PG synthesis machinery 1329:1360 However, multiple PBPs are important in clinically relevant environments, as bacteria with a minimal PG synthesis machinery became highly susceptible to cell wall-targeting antibiotics, host lytic enzymes and displayed impaired virulence in a Drosophila infection model which is dependent on the presence of specific peptidoglycan receptor proteins, namely PGRP-SA. 25951442 7 76 theme receptor 1569:1576 arg1 proteins 1578:1585 specific peptidoglycan receptor proteins 1546:1585 specific peptidoglycan receptor proteins 1546:1585 However, multiple PBPs are important in clinically relevant environments, as bacteria with a minimal PG synthesis machinery became highly susceptible to cell wall-targeting antibiotics, host lytic enzymes and displayed impaired virulence in a Drosophila infection model which is dependent on the presence of specific peptidoglycan receptor proteins, namely PGRP-SA. 25951442 7 76 theme receptor 1569:1576 arg1 PGRP-SA 1595:1601 PGRP-SA 1595:1601 PGRP-SA 1595:1601 However, multiple PBPs are important in clinically relevant environments, as bacteria with a minimal PG synthesis machinery became highly susceptible to cell wall-targeting antibiotics, host lytic enzymes and displayed impaired virulence in a Drosophila infection model which is dependent on the presence of specific peptidoglycan receptor proteins, namely PGRP-SA. 25951442 7 77 theme specific 1546:1553 arg1 proteins 1578:1585 specific peptidoglycan receptor proteins 1546:1585 specific peptidoglycan receptor proteins 1546:1585 However, multiple PBPs are important in clinically relevant environments, as bacteria with a minimal PG synthesis machinery became highly susceptible to cell wall-targeting antibiotics, host lytic enzymes and displayed impaired virulence in a Drosophila infection model which is dependent on the presence of specific peptidoglycan receptor proteins, namely PGRP-SA. 25951442 7 77 theme specific 1546:1553 arg1 PGRP-SA 1595:1601 PGRP-SA 1595:1601 PGRP-SA 1595:1601 However, multiple PBPs are important in clinically relevant environments, as bacteria with a minimal PG synthesis machinery became highly susceptible to cell wall-targeting antibiotics, host lytic enzymes and displayed impaired virulence in a Drosophila infection model which is dependent on the presence of specific peptidoglycan receptor proteins, namely PGRP-SA. 25951442 0 78 theme Antibiotic 107:116 arg1 Sacrifices 82:91 Sacrifices Virulence and Antibiotic Resistance 82:127 Sacrifices Virulence and Antibiotic Resistance 82:127 Staphylococcus aureus Survives with a Minimal Peptidoglycan Synthesis Machine but Sacrifices Virulence and Antibiotic Resistance. 25951442 0 78 theme Antibiotic 107:116 arg1 Resistance 118:127 Antibiotic Resistance 107:127 Antibiotic Resistance 107:127 Staphylococcus aureus Survives with a Minimal Peptidoglycan Synthesis Machine but Sacrifices Virulence and Antibiotic Resistance. 25951442 8 79 theme PG 1776:1777 arg1 machinery 1789:1797 the minimal PG synthesis machinery 1764:1797 the minimal PG synthesis machinery of S. aureus 1764:1810 The fact that S. aureus can grow and divide with only two active PG synthesizing enzymes shows that most of these enzymes are redundant in vitro and identifies the minimal PG synthesis machinery of S. aureus. 25951442 5 80 theme PG 942:943 arg1 machine 955:961 a minimal PG synthesis machine 932:961 a minimal PG synthesis machine 932:961 Its genome encodes a low number of proteins with PG synthesis activity (9 proteins), when compared to other model organisms, and is therefore a good model for the study of a minimal PG synthesis machine. 25951442 5 81 theme machine 955:961 arg1 study 923:927 the study 919:927 the study of a minimal PG synthesis machine 919:961 Its genome encodes a low number of proteins with PG synthesis activity (9 proteins), when compared to other model organisms, and is therefore a good model for the study of a minimal PG synthesis machine. 25951442 6 82 theme S. 1038:1039 arg1 genome 1048:1053 the S. aureus genome 1034:1053 the S. aureus genome 1034:1053 We deleted seven of the nine genes encoding PG synthesis enzymes from the S. aureus genome without affecting normal growth or cell morphology, generating a strain capable of PG biosynthesis catalyzed only by two penicillin-binding proteins, PBP1 and the bi-functional PBP2. 25951442 2 83 theme many 442:445 arg1 antibiotics 460:470 many contemporary antibiotics 442:470 many contemporary antibiotics 442:470 An example is the bacterial peptidoglycan (PG) synthesis machine, responsible for the synthesis of the main component of the cell wall and the target of many contemporary antibiotics. 25951442 2 84 theme main 392:395 arg1 component 397:405 the main component 388:405 the main component of the cell wall 388:422 An example is the bacterial peptidoglycan (PG) synthesis machine, responsible for the synthesis of the main component of the cell wall and the target of many contemporary antibiotics. 25951442 2 85 theme target 432:437 arg1 synthesis 375:383 the synthesis 371:383 the synthesis of the main component of the cell wall and the target of many contemporary antibiotics 371:470 An example is the bacterial peptidoglycan (PG) synthesis machine, responsible for the synthesis of the main component of the cell wall and the target of many contemporary antibiotics. 25951442 0 86 theme Minimal 38:44 arg1 Machine 70:76 a Minimal Peptidoglycan Synthesis Machine 36:76 a Minimal Peptidoglycan Synthesis Machine 36:76 Staphylococcus aureus Survives with a Minimal Peptidoglycan Synthesis Machine but Sacrifices Virulence and Antibiotic Resistance. 25951442 9 87 dep pathogenicity 1974:1986 arg1 the 1970:1972 the 1970:1972 the 1970:1972 However a complex molecular machine is important in environments other than in vitro growth as the expendable PG synthesis enzymes play an important role in the pathogenicity and antibiotic resistance of S. aureus. 25951442 6 88 theme synthesis 1011:1019 arg1 enzymes 1021:1027 PG synthesis enzymes 1008:1027 PG synthesis enzymes from the S. aureus genome 1008:1053 We deleted seven of the nine genes encoding PG synthesis enzymes from the S. aureus genome without affecting normal growth or cell morphology, generating a strain capable of PG biosynthesis catalyzed only by two penicillin-binding proteins, PBP1 and the bi-functional PBP2. 25951442 2 89 theme cell 414:417 arg1 wall 419:422 the cell wall 410:422 the cell wall 410:422 An example is the bacterial peptidoglycan (PG) synthesis machine, responsible for the synthesis of the main component of the cell wall and the target of many contemporary antibiotics. 25951442 0 90 theme Synthesis 60:68 arg1 Machine 70:76 a Minimal Peptidoglycan Synthesis Machine 36:76 a Minimal Peptidoglycan Synthesis Machine 36:76 Staphylococcus aureus Survives with a Minimal Peptidoglycan Synthesis Machine but Sacrifices Virulence and Antibiotic Resistance. 25951442 7 91 from important 1265:1273 arg1 environments 1298:1309 clinically relevant environments 1278:1309 clinically relevant environments 1278:1309 However, multiple PBPs are important in clinically relevant environments, as bacteria with a minimal PG synthesis machinery became highly susceptible to cell wall-targeting antibiotics, host lytic enzymes and displayed impaired virulence in a Drosophila infection model which is dependent on the presence of specific peptidoglycan receptor proteins, namely PGRP-SA. 25951442 7 92 theme multiple 1247:1254 arg1 PBPs 1256:1259 multiple PBPs 1247:1259 multiple PBPs 1247:1259 However, multiple PBPs are important in clinically relevant environments, as bacteria with a minimal PG synthesis machinery became highly susceptible to cell wall-targeting antibiotics, host lytic enzymes and displayed impaired virulence in a Drosophila infection model which is dependent on the presence of specific peptidoglycan receptor proteins, namely PGRP-SA. 25951442 2 93 theme antibiotics 460:470 arg1 target 432:437 the target 428:437 the target of many contemporary antibiotics 428:470 An example is the bacterial peptidoglycan (PG) synthesis machine, responsible for the synthesis of the main component of the cell wall and the target of many contemporary antibiotics. 25951442 2 93 theme antibiotics 460:470 arg1 component 397:405 the main component 388:405 the main component of the cell wall 388:422 An example is the bacterial peptidoglycan (PG) synthesis machine, responsible for the synthesis of the main component of the cell wall and the target of many contemporary antibiotics. 25951442 2 94 theme responsible 355:365 arg1 machine 346:352 the bacterial peptidoglycan (PG) synthesis machine 303:352 the bacterial peptidoglycan (PG) synthesis machine 303:352 An example is the bacterial peptidoglycan (PG) synthesis machine, responsible for the synthesis of the main component of the cell wall and the target of many contemporary antibiotics. 25951442 2 94 theme responsible 355:365 arg1 example 292:298 An example 289:298 An example 289:298 An example is the bacterial peptidoglycan (PG) synthesis machine, responsible for the synthesis of the main component of the cell wall and the target of many contemporary antibiotics. 25951442 6 95 theme cell 1090:1093 arg1 morphology 1095:1104 cell morphology 1090:1104 cell morphology 1090:1104 We deleted seven of the nine genes encoding PG synthesis enzymes from the S. aureus genome without affecting normal growth or cell morphology, generating a strain capable of PG biosynthesis catalyzed only by two penicillin-binding proteins, PBP1 and the bi-functional PBP2. 25951442 9 96 theme complex 1823:1829 arg1 important 1852:1860 important 1852:1860 important 1852:1860 However a complex molecular machine is important in environments other than in vitro growth as the expendable PG synthesis enzymes play an important role in the pathogenicity and antibiotic resistance of S. aureus. 25951442 9 96 theme complex 1823:1829 arg1 machine 1841:1847 a complex molecular machine 1821:1847 a complex molecular machine 1821:1847 However a complex molecular machine is important in environments other than in vitro growth as the expendable PG synthesis enzymes play an important role in the pathogenicity and antibiotic resistance of S. aureus. 25951442 7 97 theme infection 1492:1500 arg1 model 1502:1506 a Drosophila infection model 1479:1506 a Drosophila infection model which is dependent on the presence of specific peptidoglycan receptor proteins, namely PGRP-SA 1479:1601 However, multiple PBPs are important in clinically relevant environments, as bacteria with a minimal PG synthesis machinery became highly susceptible to cell wall-targeting antibiotics, host lytic enzymes and displayed impaired virulence in a Drosophila infection model which is dependent on the presence of specific peptidoglycan receptor proteins, namely PGRP-SA. 25951442 7 97 theme infection 1492:1500 arg1 dependent 1517:1525 dependent 1517:1525 dependent 1517:1525 However, multiple PBPs are important in clinically relevant environments, as bacteria with a minimal PG synthesis machinery became highly susceptible to cell wall-targeting antibiotics, host lytic enzymes and displayed impaired virulence in a Drosophila infection model which is dependent on the presence of specific peptidoglycan receptor proteins, namely PGRP-SA. 25951442 7 98 from environments 1298:1309 arg1 important 1265:1273 important 1265:1273 important 1265:1273 However, multiple PBPs are important in clinically relevant environments, as bacteria with a minimal PG synthesis machinery became highly susceptible to cell wall-targeting antibiotics, host lytic enzymes and displayed impaired virulence in a Drosophila infection model which is dependent on the presence of specific peptidoglycan receptor proteins, namely PGRP-SA. 25951442 4 99 theme Gram-positive 645:657 arg1 pathogen 659:666 a Gram-positive pathogen 643:666 a Gram-positive pathogen 643:666 Staphylococcus aureus is a Gram-positive pathogen, renowned for its resistance to many commonly used antibiotics and prevalence in hospitals. 25951442 4 99 theme Gram-positive 645:657 arg1 aureus 633:638 Staphylococcus aureus 618:638 Staphylococcus aureus 618:638 Staphylococcus aureus is a Gram-positive pathogen, renowned for its resistance to many commonly used antibiotics and prevalence in hospitals. 25951442 1 100 theme biological 267:276 arg1 functions 278:286 biological functions 267:286 biological functions 267:286 Many important cellular processes are performed by molecular machines, composed of multiple proteins that physically interact to execute biological functions. 28319083 0 0 theme recognition 73:83 arg1 mode 85:88 a new substrate recognition mode 57:88 a new substrate recognition mode 57:88 Structures of human O-GlcNAcase and its complexes reveal a new substrate recognition mode. 28319083 1 1 theme proteins 322:329 arg1 function 292:299 the function 288:299 the function of numerous cellular proteins 288:329 Human O-GlcNAcase (hOGA) is the unique enzyme responsible for the hydrolysis of the O-linked β-N-acetyl glucosamine (O-GlcNAc) modification, an essential protein glycosylation event that modulates the function of numerous cellular proteins in response to nutrients and stress. 28319083 3 2 theme monomer 655:661 arg1 domain 641:646 the catalytic domain 627:646 the catalytic domain of one monomer 627:661 We found that hOGA forms an unusual arm-in-arm homodimer in which the catalytic domain of one monomer is covered by the stalk domain of the sister monomer to create a substrate-binding cleft. 28319083 3 2 theme monomer 655:661 arg1 monomer 655:661 one monomer 651:661 one monomer 651:661 We found that hOGA forms an unusual arm-in-arm homodimer in which the catalytic domain of one monomer is covered by the stalk domain of the sister monomer to create a substrate-binding cleft. 28319083 5 3 theme biological 1161:1170 arg1 processes 1189:1197 biological and pathological processes 1161:1197 biological and pathological processes 1161:1197 These structures represent the first model of eukaryotic enzymes in the glycoside hydrolase 84 (GH84) family and provide a crucial starting point for understanding the substrate specificity of hOGA, which regulates a broad range of biological and pathological processes. 28319083 0 4 theme substrate 63:71 arg1 mode 85:88 a new substrate recognition mode 57:88 a new substrate recognition mode 57:88 Structures of human O-GlcNAcase and its complexes reveal a new substrate recognition mode. 28319083 2 5 theme glycopeptide 537:548 arg1 substrate 550:558 a glycopeptide substrate 535:558 a glycopeptide substrate 535:558 Here we report crystal structures of a truncated hOGA, which comprises the catalytic and stalk domains, in apo form, in complex with an inhibitor, and in complex with a glycopeptide substrate. 28319083 1 6 theme responsible 137:147 arg1 enzyme 130:135 the unique enzyme 119:135 the unique enzyme responsible for the hydrolysis of the O-linked β-N-acetyl glucosamine (O-GlcNAc) modification, an essential protein glycosylation event that modulates the function of numerous cellular proteins in response to nutrients and stress 119:365 Human O-GlcNAcase (hOGA) is the unique enzyme responsible for the hydrolysis of the O-linked β-N-acetyl glucosamine (O-GlcNAc) modification, an essential protein glycosylation event that modulates the function of numerous cellular proteins in response to nutrients and stress. 28319083 1 6 theme responsible 137:147 arg1 O-GlcNAcase 97:107 Human O-GlcNAcase 91:107 Human O-GlcNAcase (hOGA) 91:114 Human O-GlcNAcase (hOGA) is the unique enzyme responsible for the hydrolysis of the O-linked β-N-acetyl glucosamine (O-GlcNAc) modification, an essential protein glycosylation event that modulates the function of numerous cellular proteins in response to nutrients and stress. 28319083 2 7 with complex 522:528 arg1 substrate 550:558 a glycopeptide substrate 535:558 a glycopeptide substrate 535:558 Here we report crystal structures of a truncated hOGA, which comprises the catalytic and stalk domains, in apo form, in complex with an inhibitor, and in complex with a glycopeptide substrate. 28319083 5 8 theme hOGA 1122:1125 arg1 specificity 1107:1117 the substrate specificity 1093:1117 the substrate specificity 1093:1117 These structures represent the first model of eukaryotic enzymes in the glycoside hydrolase 84 (GH84) family and provide a crucial starting point for understanding the substrate specificity of hOGA, which regulates a broad range of biological and pathological processes. 28319083 3 9 theme catalytic 631:639 arg1 domain 641:646 the catalytic domain 627:646 the catalytic domain of one monomer 627:661 We found that hOGA forms an unusual arm-in-arm homodimer in which the catalytic domain of one monomer is covered by the stalk domain of the sister monomer to create a substrate-binding cleft. 28319083 3 9 theme catalytic 631:639 arg1 monomer 655:661 one monomer 651:661 one monomer 651:661 We found that hOGA forms an unusual arm-in-arm homodimer in which the catalytic domain of one monomer is covered by the stalk domain of the sister monomer to create a substrate-binding cleft. 28319083 4 10 theme extensive 803:811 arg1 interactions 813:824 extensive interactions 803:824 extensive interactions with the peptide substrate 803:851 Notably, the residues on the cleft surface afford extensive interactions with the peptide substrate in a recognition mode that is distinct from that of its bacterial homologs. 28319083 5 11 theme starting 1060:1067 arg1 point 1069:1073 a crucial starting point 1050:1073 a crucial starting point for understanding the substrate specificity of hOGA, which regulates a broad range of biological and pathological processes 1050:1197 These structures represent the first model of eukaryotic enzymes in the glycoside hydrolase 84 (GH84) family and provide a crucial starting point for understanding the substrate specificity of hOGA, which regulates a broad range of biological and pathological processes. 28319083 5 12 theme pathological 1176:1187 arg1 processes 1189:1197 biological and pathological processes 1161:1197 biological and pathological processes 1161:1197 These structures represent the first model of eukaryotic enzymes in the glycoside hydrolase 84 (GH84) family and provide a crucial starting point for understanding the substrate specificity of hOGA, which regulates a broad range of biological and pathological processes. 28319083 1 13 theme essential 235:243 arg1 modification 218:229 the O-linked β-N-acetyl glucosamine (O-GlcNAc) modification 171:229 the O-linked β-N-acetyl glucosamine (O-GlcNAc) modification 171:229 Human O-GlcNAcase (hOGA) is the unique enzyme responsible for the hydrolysis of the O-linked β-N-acetyl glucosamine (O-GlcNAc) modification, an essential protein glycosylation event that modulates the function of numerous cellular proteins in response to nutrients and stress. 28319083 1 13 theme essential 235:243 arg1 event 267:271 an essential protein glycosylation event 232:271 an essential protein glycosylation event that modulates the function of numerous cellular proteins in response to nutrients and stress 232:365 Human O-GlcNAcase (hOGA) is the unique enzyme responsible for the hydrolysis of the O-linked β-N-acetyl glucosamine (O-GlcNAc) modification, an essential protein glycosylation event that modulates the function of numerous cellular proteins in response to nutrients and stress. 28319083 1 14 link O-linked 175:182 arg1 modification 218:229 the O-linked β-N-acetyl glucosamine (O-GlcNAc) modification 171:229 the O-linked β-N-acetyl glucosamine (O-GlcNAc) modification 171:229 Human O-GlcNAcase (hOGA) is the unique enzyme responsible for the hydrolysis of the O-linked β-N-acetyl glucosamine (O-GlcNAc) modification, an essential protein glycosylation event that modulates the function of numerous cellular proteins in response to nutrients and stress. 28319083 1 14 link O-linked 175:182 arg1 event 267:271 an essential protein glycosylation event 232:271 an essential protein glycosylation event that modulates the function of numerous cellular proteins in response to nutrients and stress 232:365 Human O-GlcNAcase (hOGA) is the unique enzyme responsible for the hydrolysis of the O-linked β-N-acetyl glucosamine (O-GlcNAc) modification, an essential protein glycosylation event that modulates the function of numerous cellular proteins in response to nutrients and stress. 28319083 1 15 theme protein 245:251 arg1 modification 218:229 the O-linked β-N-acetyl glucosamine (O-GlcNAc) modification 171:229 the O-linked β-N-acetyl glucosamine (O-GlcNAc) modification 171:229 Human O-GlcNAcase (hOGA) is the unique enzyme responsible for the hydrolysis of the O-linked β-N-acetyl glucosamine (O-GlcNAc) modification, an essential protein glycosylation event that modulates the function of numerous cellular proteins in response to nutrients and stress. 28319083 1 15 theme protein 245:251 arg1 event 267:271 an essential protein glycosylation event 232:271 an essential protein glycosylation event that modulates the function of numerous cellular proteins in response to nutrients and stress 232:365 Human O-GlcNAcase (hOGA) is the unique enzyme responsible for the hydrolysis of the O-linked β-N-acetyl glucosamine (O-GlcNAc) modification, an essential protein glycosylation event that modulates the function of numerous cellular proteins in response to nutrients and stress. 28319083 1 16 theme numerous 304:311 arg1 proteins 322:329 numerous cellular proteins 304:329 numerous cellular proteins 304:329 Human O-GlcNAcase (hOGA) is the unique enzyme responsible for the hydrolysis of the O-linked β-N-acetyl glucosamine (O-GlcNAc) modification, an essential protein glycosylation event that modulates the function of numerous cellular proteins in response to nutrients and stress. 28319083 5 17 from model 966:970 arg1 family 1031:1036 the glycoside hydrolase 84 (GH84) family 997:1036 the glycoside hydrolase 84 (GH84) family 997:1036 These structures represent the first model of eukaryotic enzymes in the glycoside hydrolase 84 (GH84) family and provide a crucial starting point for understanding the substrate specificity of hOGA, which regulates a broad range of biological and pathological processes. 28319083 2 18 theme apo 475:477 arg1 form 479:482 apo form 475:482 apo form 475:482 Here we report crystal structures of a truncated hOGA, which comprises the catalytic and stalk domains, in apo form, in complex with an inhibitor, and in complex with a glycopeptide substrate. 28319083 4 19 from residues 766:773 arg1 surface 788:794 the cleft surface 778:794 the cleft surface 778:794 Notably, the residues on the cleft surface afford extensive interactions with the peptide substrate in a recognition mode that is distinct from that of its bacterial homologs. 28319083 3 20 theme substrate-binding 728:744 arg1 cleft 746:750 a substrate-binding cleft 726:750 a substrate-binding cleft 726:750 We found that hOGA forms an unusual arm-in-arm homodimer in which the catalytic domain of one monomer is covered by the stalk domain of the sister monomer to create a substrate-binding cleft. 28319083 2 21 theme stalk 457:461 arg1 domains 463:469 the catalytic and stalk domains 439:469 the catalytic and stalk domains 439:469 Here we report crystal structures of a truncated hOGA, which comprises the catalytic and stalk domains, in apo form, in complex with an inhibitor, and in complex with a glycopeptide substrate. 28319083 5 22 theme broad 1146:1150 arg1 range 1152:1156 a broad range 1144:1156 a broad range of biological and pathological processes 1144:1197 These structures represent the first model of eukaryotic enzymes in the glycoside hydrolase 84 (GH84) family and provide a crucial starting point for understanding the substrate specificity of hOGA, which regulates a broad range of biological and pathological processes. 28319083 3 23 theme stalk 681:685 arg1 domain 687:692 the stalk domain 677:692 the stalk domain of the sister monomer to create a substrate-binding cleft 677:750 We found that hOGA forms an unusual arm-in-arm homodimer in which the catalytic domain of one monomer is covered by the stalk domain of the sister monomer to create a substrate-binding cleft. 28319083 3 23 theme stalk 681:685 arg1 monomer 708:714 the sister monomer 697:714 the sister monomer 697:714 We found that hOGA forms an unusual arm-in-arm homodimer in which the catalytic domain of one monomer is covered by the stalk domain of the sister monomer to create a substrate-binding cleft. 28319083 1 24 theme glycosylation 253:265 arg1 modification 218:229 the O-linked β-N-acetyl glucosamine (O-GlcNAc) modification 171:229 the O-linked β-N-acetyl glucosamine (O-GlcNAc) modification 171:229 Human O-GlcNAcase (hOGA) is the unique enzyme responsible for the hydrolysis of the O-linked β-N-acetyl glucosamine (O-GlcNAc) modification, an essential protein glycosylation event that modulates the function of numerous cellular proteins in response to nutrients and stress. 28319083 1 24 theme glycosylation 253:265 arg1 event 267:271 an essential protein glycosylation event 232:271 an essential protein glycosylation event that modulates the function of numerous cellular proteins in response to nutrients and stress 232:365 Human O-GlcNAcase (hOGA) is the unique enzyme responsible for the hydrolysis of the O-linked β-N-acetyl glucosamine (O-GlcNAc) modification, an essential protein glycosylation event that modulates the function of numerous cellular proteins in response to nutrients and stress. 28319083 5 25 theme enzymes 986:992 arg1 model 966:970 the first model 956:970 the first model of eukaryotic enzymes in the glycoside hydrolase 84 (GH84) family 956:1036 These structures represent the first model of eukaryotic enzymes in the glycoside hydrolase 84 (GH84) family and provide a crucial starting point for understanding the substrate specificity of hOGA, which regulates a broad range of biological and pathological processes. 28319083 4 26 theme cleft 782:786 arg1 surface 788:794 the cleft surface 778:794 the cleft surface 778:794 Notably, the residues on the cleft surface afford extensive interactions with the peptide substrate in a recognition mode that is distinct from that of its bacterial homologs. 28319083 0 27 theme O-GlcNAcase 20:30 arg1 Structures 0:9 Structures 0:9 Structures of human O-GlcNAcase and its complexes 0:48 Structures of human O-GlcNAcase and its complexes reveal a new substrate recognition mode. 28319083 1 28 theme Human 91:95 arg1 enzyme 130:135 the unique enzyme 119:135 the unique enzyme responsible for the hydrolysis of the O-linked β-N-acetyl glucosamine (O-GlcNAc) modification, an essential protein glycosylation event that modulates the function of numerous cellular proteins in response to nutrients and stress 119:365 Human O-GlcNAcase (hOGA) is the unique enzyme responsible for the hydrolysis of the O-linked β-N-acetyl glucosamine (O-GlcNAc) modification, an essential protein glycosylation event that modulates the function of numerous cellular proteins in response to nutrients and stress. 28319083 1 28 theme Human 91:95 arg1 hOGA 110:113 hOGA 110:113 hOGA 110:113 Human O-GlcNAcase (hOGA) is the unique enzyme responsible for the hydrolysis of the O-linked β-N-acetyl glucosamine (O-GlcNAc) modification, an essential protein glycosylation event that modulates the function of numerous cellular proteins in response to nutrients and stress. 28319083 1 28 theme Human 91:95 arg1 O-GlcNAcase 97:107 Human O-GlcNAcase 91:107 Human O-GlcNAcase (hOGA) 91:114 Human O-GlcNAcase (hOGA) is the unique enzyme responsible for the hydrolysis of the O-linked β-N-acetyl glucosamine (O-GlcNAc) modification, an essential protein glycosylation event that modulates the function of numerous cellular proteins in response to nutrients and stress. 28319083 2 29 gly glycopeptide 537:548 arg2 glycopeptide 537:548 glycopeptide 537:548 glycopeptide 537:548 Here we report crystal structures of a truncated hOGA, which comprises the catalytic and stalk domains, in apo form, in complex with an inhibitor, and in complex with a glycopeptide substrate. 28319083 0 30 theme human 14:18 arg1 O-GlcNAcase 20:30 human O-GlcNAcase 14:30 human O-GlcNAcase 14:30 Structures of human O-GlcNAcase and its complexes reveal a new substrate recognition mode. 28319083 5 31 theme substrate 1097:1105 arg1 specificity 1107:1117 the substrate specificity 1093:1117 the substrate specificity 1093:1117 These structures represent the first model of eukaryotic enzymes in the glycoside hydrolase 84 (GH84) family and provide a crucial starting point for understanding the substrate specificity of hOGA, which regulates a broad range of biological and pathological processes. 28319083 1 32 theme O-linked 175:182 arg1 modification 218:229 the O-linked β-N-acetyl glucosamine (O-GlcNAc) modification 171:229 the O-linked β-N-acetyl glucosamine (O-GlcNAc) modification 171:229 Human O-GlcNAcase (hOGA) is the unique enzyme responsible for the hydrolysis of the O-linked β-N-acetyl glucosamine (O-GlcNAc) modification, an essential protein glycosylation event that modulates the function of numerous cellular proteins in response to nutrients and stress. 28319083 1 32 theme O-linked 175:182 arg1 event 267:271 an essential protein glycosylation event 232:271 an essential protein glycosylation event that modulates the function of numerous cellular proteins in response to nutrients and stress 232:365 Human O-GlcNAcase (hOGA) is the unique enzyme responsible for the hydrolysis of the O-linked β-N-acetyl glucosamine (O-GlcNAc) modification, an essential protein glycosylation event that modulates the function of numerous cellular proteins in response to nutrients and stress. 28319083 4 33 theme recognition 858:868 arg1 mode 870:873 a recognition mode 856:873 a recognition mode that is distinct from that of its bacterial homologs 856:926 Notably, the residues on the cleft surface afford extensive interactions with the peptide substrate in a recognition mode that is distinct from that of its bacterial homologs. 28319083 4 33 theme recognition 858:868 arg1 distinct 883:890 distinct 883:890 distinct 883:890 Notably, the residues on the cleft surface afford extensive interactions with the peptide substrate in a recognition mode that is distinct from that of its bacterial homologs. 28319083 3 34 theme unusual 589:595 arg1 homodimer 608:616 an unusual arm-in-arm homodimer 586:616 an unusual arm-in-arm homodimer in which the catalytic domain of one monomer is covered by the stalk domain of the sister monomer to create a substrate-binding cleft 586:750 We found that hOGA forms an unusual arm-in-arm homodimer in which the catalytic domain of one monomer is covered by the stalk domain of the sister monomer to create a substrate-binding cleft. 28319083 4 35 with interactions 813:824 arg1 substrate 843:851 the peptide substrate 831:851 the peptide substrate 831:851 Notably, the residues on the cleft surface afford extensive interactions with the peptide substrate in a recognition mode that is distinct from that of its bacterial homologs. 28319083 1 36 theme β-N-acetyl 184:193 arg1 modification 218:229 the O-linked β-N-acetyl glucosamine (O-GlcNAc) modification 171:229 the O-linked β-N-acetyl glucosamine (O-GlcNAc) modification 171:229 Human O-GlcNAcase (hOGA) is the unique enzyme responsible for the hydrolysis of the O-linked β-N-acetyl glucosamine (O-GlcNAc) modification, an essential protein glycosylation event that modulates the function of numerous cellular proteins in response to nutrients and stress. 28319083 1 36 theme β-N-acetyl 184:193 arg1 event 267:271 an essential protein glycosylation event 232:271 an essential protein glycosylation event that modulates the function of numerous cellular proteins in response to nutrients and stress 232:365 Human O-GlcNAcase (hOGA) is the unique enzyme responsible for the hydrolysis of the O-linked β-N-acetyl glucosamine (O-GlcNAc) modification, an essential protein glycosylation event that modulates the function of numerous cellular proteins in response to nutrients and stress. 28319083 2 37 theme catalytic 443:451 arg1 domains 463:469 the catalytic and stalk domains 439:469 the catalytic and stalk domains 439:469 Here we report crystal structures of a truncated hOGA, which comprises the catalytic and stalk domains, in apo form, in complex with an inhibitor, and in complex with a glycopeptide substrate. 28319083 3 38 theme sister 701:706 arg1 monomer 708:714 the sister monomer 697:714 the sister monomer 697:714 We found that hOGA forms an unusual arm-in-arm homodimer in which the catalytic domain of one monomer is covered by the stalk domain of the sister monomer to create a substrate-binding cleft. 28319083 4 39 theme bacterial 909:917 arg1 homologs 919:926 its bacterial homologs 905:926 its bacterial homologs 905:926 Notably, the residues on the cleft surface afford extensive interactions with the peptide substrate in a recognition mode that is distinct from that of its bacterial homologs. 28319083 5 40 theme glycoside 1001:1009 arg1 family 1031:1036 the glycoside hydrolase 84 (GH84) family 997:1036 the glycoside hydrolase 84 (GH84) family 997:1036 These structures represent the first model of eukaryotic enzymes in the glycoside hydrolase 84 (GH84) family and provide a crucial starting point for understanding the substrate specificity of hOGA, which regulates a broad range of biological and pathological processes. 28319083 2 41 theme hOGA 417:420 arg1 structures 391:400 crystal structures 383:400 crystal structures of a truncated hOGA, which comprises the catalytic and stalk domains, in apo form, in complex with an inhibitor, and in complex with a glycopeptide substrate 383:558 Here we report crystal structures of a truncated hOGA, which comprises the catalytic and stalk domains, in apo form, in complex with an inhibitor, and in complex with a glycopeptide substrate. 28319083 1 42 theme glucosamine 195:205 arg1 modification 218:229 the O-linked β-N-acetyl glucosamine (O-GlcNAc) modification 171:229 the O-linked β-N-acetyl glucosamine (O-GlcNAc) modification 171:229 Human O-GlcNAcase (hOGA) is the unique enzyme responsible for the hydrolysis of the O-linked β-N-acetyl glucosamine (O-GlcNAc) modification, an essential protein glycosylation event that modulates the function of numerous cellular proteins in response to nutrients and stress. 28319083 1 42 theme glucosamine 195:205 arg1 event 267:271 an essential protein glycosylation event 232:271 an essential protein glycosylation event that modulates the function of numerous cellular proteins in response to nutrients and stress 232:365 Human O-GlcNAcase (hOGA) is the unique enzyme responsible for the hydrolysis of the O-linked β-N-acetyl glucosamine (O-GlcNAc) modification, an essential protein glycosylation event that modulates the function of numerous cellular proteins in response to nutrients and stress. 28319083 5 43 from family 1031:1036 arg1 model 966:970 the first model 956:970 the first model of eukaryotic enzymes in the glycoside hydrolase 84 (GH84) family 956:1036 These structures represent the first model of eukaryotic enzymes in the glycoside hydrolase 84 (GH84) family and provide a crucial starting point for understanding the substrate specificity of hOGA, which regulates a broad range of biological and pathological processes. 28319083 3 44 theme monomer 708:714 arg1 domain 687:692 the stalk domain 677:692 the stalk domain of the sister monomer to create a substrate-binding cleft 677:750 We found that hOGA forms an unusual arm-in-arm homodimer in which the catalytic domain of one monomer is covered by the stalk domain of the sister monomer to create a substrate-binding cleft. 28319083 3 44 theme monomer 708:714 arg1 monomer 708:714 the sister monomer 697:714 the sister monomer 697:714 We found that hOGA forms an unusual arm-in-arm homodimer in which the catalytic domain of one monomer is covered by the stalk domain of the sister monomer to create a substrate-binding cleft. 28319083 5 45 theme hydrolase 1011:1019 arg1 family 1031:1036 the glycoside hydrolase 84 (GH84) family 997:1036 the glycoside hydrolase 84 (GH84) family 997:1036 These structures represent the first model of eukaryotic enzymes in the glycoside hydrolase 84 (GH84) family and provide a crucial starting point for understanding the substrate specificity of hOGA, which regulates a broad range of biological and pathological processes. 28319083 5 46 theme GH84 1025:1028 arg1 family 1031:1036 the glycoside hydrolase 84 (GH84) family 997:1036 the glycoside hydrolase 84 (GH84) family 997:1036 These structures represent the first model of eukaryotic enzymes in the glycoside hydrolase 84 (GH84) family and provide a crucial starting point for understanding the substrate specificity of hOGA, which regulates a broad range of biological and pathological processes. 28319083 0 47 theme complexes 40:48 arg1 Structures 0:9 Structures 0:9 Structures of human O-GlcNAcase and its complexes 0:48 Structures of human O-GlcNAcase and its complexes reveal a new substrate recognition mode. 28319083 5 48 theme first 960:964 arg1 model 966:970 the first model 956:970 the first model of eukaryotic enzymes in the glycoside hydrolase 84 (GH84) family 956:1036 These structures represent the first model of eukaryotic enzymes in the glycoside hydrolase 84 (GH84) family and provide a crucial starting point for understanding the substrate specificity of hOGA, which regulates a broad range of biological and pathological processes. 28319083 5 49 theme crucial 1052:1058 arg1 point 1069:1073 a crucial starting point 1050:1073 a crucial starting point for understanding the substrate specificity of hOGA, which regulates a broad range of biological and pathological processes 1050:1197 These structures represent the first model of eukaryotic enzymes in the glycoside hydrolase 84 (GH84) family and provide a crucial starting point for understanding the substrate specificity of hOGA, which regulates a broad range of biological and pathological processes. 28319083 5 50 theme processes 1189:1197 arg1 range 1152:1156 a broad range 1144:1156 a broad range of biological and pathological processes 1144:1197 These structures represent the first model of eukaryotic enzymes in the glycoside hydrolase 84 (GH84) family and provide a crucial starting point for understanding the substrate specificity of hOGA, which regulates a broad range of biological and pathological processes. 28319083 1 51 dep nutrients 346:354 arg1 response 334:341 response 334:341 response 334:341 Human O-GlcNAcase (hOGA) is the unique enzyme responsible for the hydrolysis of the O-linked β-N-acetyl glucosamine (O-GlcNAc) modification, an essential protein glycosylation event that modulates the function of numerous cellular proteins in response to nutrients and stress. 28319083 4 52 theme peptide 835:841 arg1 substrate 843:851 the peptide substrate 831:851 the peptide substrate 831:851 Notably, the residues on the cleft surface afford extensive interactions with the peptide substrate in a recognition mode that is distinct from that of its bacterial homologs. 28319083 2 53 with complex 488:494 arg1 inhibitor 504:512 an inhibitor 501:512 an inhibitor 501:512 Here we report crystal structures of a truncated hOGA, which comprises the catalytic and stalk domains, in apo form, in complex with an inhibitor, and in complex with a glycopeptide substrate. 28319083 3 54 theme arm-in-arm 597:606 arg1 homodimer 608:616 an unusual arm-in-arm homodimer 586:616 an unusual arm-in-arm homodimer in which the catalytic domain of one monomer is covered by the stalk domain of the sister monomer to create a substrate-binding cleft 586:750 We found that hOGA forms an unusual arm-in-arm homodimer in which the catalytic domain of one monomer is covered by the stalk domain of the sister monomer to create a substrate-binding cleft. 28319083 2 55 from structures 391:400 arg1 form 479:482 apo form 475:482 apo form 475:482 Here we report crystal structures of a truncated hOGA, which comprises the catalytic and stalk domains, in apo form, in complex with an inhibitor, and in complex with a glycopeptide substrate. 28319083 2 55 from structures 391:400 arg1 complex 488:494 complex 488:494 complex with an inhibitor 488:512 Here we report crystal structures of a truncated hOGA, which comprises the catalytic and stalk domains, in apo form, in complex with an inhibitor, and in complex with a glycopeptide substrate. 28319083 2 55 from structures 391:400 arg1 complex 522:528 complex 522:528 complex with a glycopeptide substrate 522:558 Here we report crystal structures of a truncated hOGA, which comprises the catalytic and stalk domains, in apo form, in complex with an inhibitor, and in complex with a glycopeptide substrate. 28319083 5 56 theme eukaryotic 975:984 arg1 enzymes 986:992 eukaryotic enzymes 975:992 eukaryotic enzymes in the glycoside hydrolase 84 (GH84) family 975:1036 These structures represent the first model of eukaryotic enzymes in the glycoside hydrolase 84 (GH84) family and provide a crucial starting point for understanding the substrate specificity of hOGA, which regulates a broad range of biological and pathological processes. 28319083 1 57 theme O-GlcNAc 208:215 arg1 modification 218:229 the O-linked β-N-acetyl glucosamine (O-GlcNAc) modification 171:229 the O-linked β-N-acetyl glucosamine (O-GlcNAc) modification 171:229 Human O-GlcNAcase (hOGA) is the unique enzyme responsible for the hydrolysis of the O-linked β-N-acetyl glucosamine (O-GlcNAc) modification, an essential protein glycosylation event that modulates the function of numerous cellular proteins in response to nutrients and stress. 28319083 1 57 theme O-GlcNAc 208:215 arg1 event 267:271 an essential protein glycosylation event 232:271 an essential protein glycosylation event that modulates the function of numerous cellular proteins in response to nutrients and stress 232:365 Human O-GlcNAcase (hOGA) is the unique enzyme responsible for the hydrolysis of the O-linked β-N-acetyl glucosamine (O-GlcNAc) modification, an essential protein glycosylation event that modulates the function of numerous cellular proteins in response to nutrients and stress. 28319083 0 58 theme new 59:61 arg1 mode 85:88 a new substrate recognition mode 57:88 a new substrate recognition mode 57:88 Structures of human O-GlcNAcase and its complexes reveal a new substrate recognition mode. 28319083 2 59 theme crystal 383:389 arg1 structures 391:400 crystal structures 383:400 crystal structures of a truncated hOGA, which comprises the catalytic and stalk domains, in apo form, in complex with an inhibitor, and in complex with a glycopeptide substrate 383:558 Here we report crystal structures of a truncated hOGA, which comprises the catalytic and stalk domains, in apo form, in complex with an inhibitor, and in complex with a glycopeptide substrate. 28319083 4 60 from that 897:900 arg1 mode 870:873 a recognition mode 856:873 a recognition mode that is distinct from that of its bacterial homologs 856:926 Notably, the residues on the cleft surface afford extensive interactions with the peptide substrate in a recognition mode that is distinct from that of its bacterial homologs. 28319083 4 60 from that 897:900 arg1 distinct 883:890 distinct 883:890 distinct 883:890 Notably, the residues on the cleft surface afford extensive interactions with the peptide substrate in a recognition mode that is distinct from that of its bacterial homologs. 28319083 5 61 from enzymes 986:992 arg1 family 1031:1036 the glycoside hydrolase 84 (GH84) family 997:1036 the glycoside hydrolase 84 (GH84) family 997:1036 These structures represent the first model of eukaryotic enzymes in the glycoside hydrolase 84 (GH84) family and provide a crucial starting point for understanding the substrate specificity of hOGA, which regulates a broad range of biological and pathological processes. 28319083 1 62 theme cellular 313:320 arg1 proteins 322:329 numerous cellular proteins 304:329 numerous cellular proteins 304:329 Human O-GlcNAcase (hOGA) is the unique enzyme responsible for the hydrolysis of the O-linked β-N-acetyl glucosamine (O-GlcNAc) modification, an essential protein glycosylation event that modulates the function of numerous cellular proteins in response to nutrients and stress. 28319083 2 63 theme truncated 407:415 arg1 hOGA 417:420 a truncated hOGA 405:420 a truncated hOGA 405:420 Here we report crystal structures of a truncated hOGA, which comprises the catalytic and stalk domains, in apo form, in complex with an inhibitor, and in complex with a glycopeptide substrate. 28319083 1 64 theme unique 123:128 arg1 enzyme 130:135 the unique enzyme 119:135 the unique enzyme responsible for the hydrolysis of the O-linked β-N-acetyl glucosamine (O-GlcNAc) modification, an essential protein glycosylation event that modulates the function of numerous cellular proteins in response to nutrients and stress 119:365 Human O-GlcNAcase (hOGA) is the unique enzyme responsible for the hydrolysis of the O-linked β-N-acetyl glucosamine (O-GlcNAc) modification, an essential protein glycosylation event that modulates the function of numerous cellular proteins in response to nutrients and stress. 28319083 1 64 theme unique 123:128 arg1 O-GlcNAcase 97:107 Human O-GlcNAcase 91:107 Human O-GlcNAcase (hOGA) 91:114 Human O-GlcNAcase (hOGA) is the unique enzyme responsible for the hydrolysis of the O-linked β-N-acetyl glucosamine (O-GlcNAc) modification, an essential protein glycosylation event that modulates the function of numerous cellular proteins in response to nutrients and stress. 28319083 1 65 theme modification 218:229 arg1 hydrolysis 157:166 the hydrolysis 153:166 the hydrolysis of the O-linked β-N-acetyl glucosamine (O-GlcNAc) modification, an essential protein glycosylation event that modulates the function of numerous cellular proteins in response to nutrients and stress 153:365 Human O-GlcNAcase (hOGA) is the unique enzyme responsible for the hydrolysis of the O-linked β-N-acetyl glucosamine (O-GlcNAc) modification, an essential protein glycosylation event that modulates the function of numerous cellular proteins in response to nutrients and stress. 27610614 2 0 gly glycoproteins 270:282 arg1 glycoproteins 270:282 glycoproteins 270:282 glycoproteins which are secreted from the bloodstream or produced by salivary glands 270:353 Saliva is rich in glycoproteins which are secreted from the bloodstream or produced by salivary glands. 27610614 5 1 theme days 728:731 arg1 period 733:738 a 5 days period 724:738 a 5 days period 724:738 This study aims to analyse and compare O-glycans released from whole human mouth saliva collected 3 times a day from a healthy individual over a 5 days period. 27610614 3 2 from abundant 423:430 arg1 saliva 441:446 human saliva 435:446 human saliva 435:446 Mucins, which are highly O-glycosylated proteins, are particularly abundant in human saliva. 27610614 1 3 theme disease 145:151 arg1 biomarkers 153:162 disease biomarkers 145:162 disease biomarkers 145:162 The study of saliva O-glycosylation is receiving increasing attention due to the potential of glycans for disease biomarkers, but also due to easy access and non-invasive collection of saliva as biological fluid. 27610614 2 4 from glycoproteins 270:282 arg1 rich 262:265 rich 262:265 rich 262:265 Saliva is rich in glycoproteins which are secreted from the bloodstream or produced by salivary glands. 27610614 4 5 theme disease 561:567 arg1 biomarkers 569:578 potential disease biomarkers 551:578 potential disease biomarkers 551:578 Their glycosylation is associated with blood group and secretor status, and represents a reservoir of potential disease biomarkers. 27610614 3 6 gly O-glycosylated 381:394 arg1 Mucins 356:361 Mucins 356:361 Mucins 356:361 Mucins, which are highly O-glycosylated proteins, are particularly abundant in human saliva. 27610614 3 6 gly O-glycosylated 381:394 arg1 proteins 396:403 highly O-glycosylated proteins 374:403 highly O-glycosylated proteins 374:403 Mucins, which are highly O-glycosylated proteins, are particularly abundant in human saliva. 27610614 1 7 theme biological 234:243 arg1 fluid 245:249 biological fluid 234:249 biological fluid 234:249 The study of saliva O-glycosylation is receiving increasing attention due to the potential of glycans for disease biomarkers, but also due to easy access and non-invasive collection of saliva as biological fluid. 27610614 6 8 link O-linked 741:748 arg1 glycans 750:756 O-linked glycans 741:756 O-linked glycans 741:756 O-linked glycans were released by hydrazinolysis, labelled with procainamide and analysed by ultra-high performance liquid chromatography with fluorescence detection (UHPLC-FLR) coupled to electrospray ionization mass spectrometry (ESI-MS/MS). 27610614 5 9 theme whole 644:648 arg1 saliva 662:667 whole human mouth saliva 644:667 whole human mouth saliva collected 3 times a day from a healthy individual over a 5 days period 644:738 This study aims to analyse and compare O-glycans released from whole human mouth saliva collected 3 times a day from a healthy individual over a 5 days period. 27610614 5 10 theme healthy 700:706 arg1 individual 708:717 a healthy individual 698:717 a healthy individual 698:717 This study aims to analyse and compare O-glycans released from whole human mouth saliva collected 3 times a day from a healthy individual over a 5 days period. 27610614 6 11 theme fluorescence 884:895 arg1 UHPLC-FLR 908:916 UHPLC-FLR 908:916 UHPLC-FLR 908:916 O-linked glycans were released by hydrazinolysis, labelled with procainamide and analysed by ultra-high performance liquid chromatography with fluorescence detection (UHPLC-FLR) coupled to electrospray ionization mass spectrometry (ESI-MS/MS). 27610614 6 11 theme fluorescence 884:895 arg1 detection 897:905 fluorescence detection 884:905 fluorescence detection (UHPLC-FLR) 884:917 O-linked glycans were released by hydrazinolysis, labelled with procainamide and analysed by ultra-high performance liquid chromatography with fluorescence detection (UHPLC-FLR) coupled to electrospray ionization mass spectrometry (ESI-MS/MS). 27610614 5 12 theme human 650:654 arg1 saliva 662:667 whole human mouth saliva 644:667 whole human mouth saliva collected 3 times a day from a healthy individual over a 5 days period 644:738 This study aims to analyse and compare O-glycans released from whole human mouth saliva collected 3 times a day from a healthy individual over a 5 days period. 27610614 1 13 theme saliva 52:57 arg1 O-glycosylation 59:73 saliva O-glycosylation 52:73 saliva O-glycosylation 52:73 The study of saliva O-glycosylation is receiving increasing attention due to the potential of glycans for disease biomarkers, but also due to easy access and non-invasive collection of saliva as biological fluid. 27610614 5 14 dep times 681:685 arg1 day 689:691 a day 687:691 3 times a day from a healthy individual 679:717 This study aims to analyse and compare O-glycans released from whole human mouth saliva collected 3 times a day from a healthy individual over a 5 days period. 27610614 5 14 dep times 681:685 arg1 period 733:738 a 5 days period 724:738 a 5 days period 724:738 This study aims to analyse and compare O-glycans released from whole human mouth saliva collected 3 times a day from a healthy individual over a 5 days period. 27610614 4 15 theme biomarkers 569:578 arg1 reservoir 538:546 a reservoir 536:546 a reservoir of potential disease biomarkers 536:578 Their glycosylation is associated with blood group and secretor status, and represents a reservoir of potential disease biomarkers. 27610614 1 16 theme O-glycosylation 59:73 arg1 study 43:47 The study 39:47 The study of saliva O-glycosylation 39:73 The study of saliva O-glycosylation is receiving increasing attention due to the potential of glycans for disease biomarkers, but also due to easy access and non-invasive collection of saliva as biological fluid. 27610614 8 17 from O-glycosylation 1130:1144 arg1 saliva 1155:1160 human saliva 1149:1160 human saliva 1149:1160 Our data demonstrates that the O-glycosylation in human saliva changes significantly during the day. 27610614 7 18 used used 1069:1072 arg2 method 1008:1013 The sample preparation method 985:1013 The sample preparation method 985:1013 The sample preparation method showed excellent reproducibility and can therefore be used for biomarker discovery. 27610614 6 19 theme liquid 857:862 arg1 chromatography 864:877 ultra-high performance liquid chromatography 834:877 ultra-high performance liquid chromatography with fluorescence detection (UHPLC-FLR) coupled to electrospray ionization mass spectrometry (ESI-MS/MS) 834:982 O-linked glycans were released by hydrazinolysis, labelled with procainamide and analysed by ultra-high performance liquid chromatography with fluorescence detection (UHPLC-FLR) coupled to electrospray ionization mass spectrometry (ESI-MS/MS). 27610614 6 20 theme O-linked 741:748 arg1 glycans 750:756 O-linked glycans 741:756 O-linked glycans 741:756 O-linked glycans were released by hydrazinolysis, labelled with procainamide and analysed by ultra-high performance liquid chromatography with fluorescence detection (UHPLC-FLR) coupled to electrospray ionization mass spectrometry (ESI-MS/MS). 27610614 1 21 theme increasing 88:97 arg1 attention 99:107 increasing attention 88:107 increasing attention due to the potential of glycans for disease biomarkers, but also due to easy access and non-invasive collection of saliva 88:229 The study of saliva O-glycosylation is receiving increasing attention due to the potential of glycans for disease biomarkers, but also due to easy access and non-invasive collection of saliva as biological fluid. 27610614 0 22 theme Salivary 19:26 arg1 O-Glycome 28:36 Human Salivary O-Glycome 13:36 Human Salivary O-Glycome 13:36 Variation of Human Salivary O-Glycome. 27610614 6 23 with chromatography 864:877 arg1 UHPLC-FLR 908:916 UHPLC-FLR 908:916 UHPLC-FLR 908:916 O-linked glycans were released by hydrazinolysis, labelled with procainamide and analysed by ultra-high performance liquid chromatography with fluorescence detection (UHPLC-FLR) coupled to electrospray ionization mass spectrometry (ESI-MS/MS). 27610614 6 23 with chromatography 864:877 arg1 detection 897:905 fluorescence detection 884:905 fluorescence detection (UHPLC-FLR) 884:917 O-linked glycans were released by hydrazinolysis, labelled with procainamide and analysed by ultra-high performance liquid chromatography with fluorescence detection (UHPLC-FLR) coupled to electrospray ionization mass spectrometry (ESI-MS/MS). 27610614 7 24 theme excellent 1022:1030 arg1 reproducibility 1032:1046 excellent reproducibility 1022:1046 excellent reproducibility 1022:1046 The sample preparation method showed excellent reproducibility and can therefore be used for biomarker discovery. 27610614 0 25 theme Human 13:17 arg1 O-Glycome 28:36 Human Salivary O-Glycome 13:36 Human Salivary O-Glycome 13:36 Variation of Human Salivary O-Glycome. 27610614 7 26 theme biomarker 1078:1086 arg1 discovery 1088:1096 biomarker discovery 1078:1096 biomarker discovery 1078:1096 The sample preparation method showed excellent reproducibility and can therefore be used for biomarker discovery. 27610614 5 27 from individual 708:717 arg1 day 689:691 a day 687:691 3 times a day from a healthy individual 679:717 This study aims to analyse and compare O-glycans released from whole human mouth saliva collected 3 times a day from a healthy individual over a 5 days period. 27610614 1 28 theme due 109:111 arg1 attention 99:107 increasing attention 88:107 increasing attention due to the potential of glycans for disease biomarkers, but also due to easy access and non-invasive collection of saliva 88:229 The study of saliva O-glycosylation is receiving increasing attention due to the potential of glycans for disease biomarkers, but also due to easy access and non-invasive collection of saliva as biological fluid. 27610614 1 29 theme easy 181:184 arg1 access 186:191 easy access 181:191 easy access 181:191 The study of saliva O-glycosylation is receiving increasing attention due to the potential of glycans for disease biomarkers, but also due to easy access and non-invasive collection of saliva as biological fluid. 27610614 3 30 theme O-glycosylated 381:394 arg1 Mucins 356:361 Mucins 356:361 Mucins 356:361 Mucins, which are highly O-glycosylated proteins, are particularly abundant in human saliva. 27610614 3 30 theme O-glycosylated 381:394 arg1 proteins 396:403 highly O-glycosylated proteins 374:403 highly O-glycosylated proteins 374:403 Mucins, which are highly O-glycosylated proteins, are particularly abundant in human saliva. 27610614 6 31 theme mass 954:957 arg1 spectrometry 959:970 electrospray ionization mass spectrometry 930:970 electrospray ionization mass spectrometry (ESI-MS/MS) 930:982 O-linked glycans were released by hydrazinolysis, labelled with procainamide and analysed by ultra-high performance liquid chromatography with fluorescence detection (UHPLC-FLR) coupled to electrospray ionization mass spectrometry (ESI-MS/MS). 27610614 6 31 theme mass 954:957 arg1 ESI-MS/MS 973:981 ESI-MS/MS 973:981 ESI-MS/MS 973:981 O-linked glycans were released by hydrazinolysis, labelled with procainamide and analysed by ultra-high performance liquid chromatography with fluorescence detection (UHPLC-FLR) coupled to electrospray ionization mass spectrometry (ESI-MS/MS). 27610614 6 32 theme ultra-high 834:843 arg1 chromatography 864:877 ultra-high performance liquid chromatography 834:877 ultra-high performance liquid chromatography with fluorescence detection (UHPLC-FLR) coupled to electrospray ionization mass spectrometry (ESI-MS/MS) 834:982 O-linked glycans were released by hydrazinolysis, labelled with procainamide and analysed by ultra-high performance liquid chromatography with fluorescence detection (UHPLC-FLR) coupled to electrospray ionization mass spectrometry (ESI-MS/MS). 27610614 8 33 gly O-glycosylation 1130:1144 arg1 saliva 1155:1160 human saliva 1149:1160 human saliva 1149:1160 Our data demonstrates that the O-glycosylation in human saliva changes significantly during the day. 27610614 0 34 theme O-Glycome 28:36 arg1 Variation 0:8 Variation 0:8 Variation of Human Salivary O-Glycome 0:36 Variation of Human Salivary O-Glycome. 27610614 6 35 theme ionization 943:952 arg1 spectrometry 959:970 electrospray ionization mass spectrometry 930:970 electrospray ionization mass spectrometry (ESI-MS/MS) 930:982 O-linked glycans were released by hydrazinolysis, labelled with procainamide and analysed by ultra-high performance liquid chromatography with fluorescence detection (UHPLC-FLR) coupled to electrospray ionization mass spectrometry (ESI-MS/MS). 27610614 6 35 theme ionization 943:952 arg1 ESI-MS/MS 973:981 ESI-MS/MS 973:981 ESI-MS/MS 973:981 O-linked glycans were released by hydrazinolysis, labelled with procainamide and analysed by ultra-high performance liquid chromatography with fluorescence detection (UHPLC-FLR) coupled to electrospray ionization mass spectrometry (ESI-MS/MS). 27610614 4 36 theme potential 551:559 arg1 biomarkers 569:578 potential disease biomarkers 551:578 potential disease biomarkers 551:578 Their glycosylation is associated with blood group and secretor status, and represents a reservoir of potential disease biomarkers. 27610614 9 37 theme salivary 1247:1254 arg1 concentrations 1256:1269 the salivary concentrations 1243:1269 the salivary concentrations of specific proteins 1243:1290 These changes may be related to changes in the salivary concentrations of specific proteins. 27610614 3 38 theme human 435:439 arg1 saliva 441:446 human saliva 435:446 human saliva 435:446 Mucins, which are highly O-glycosylated proteins, are particularly abundant in human saliva. 27610614 4 39 theme secretor 504:511 arg1 status 513:518 secretor status 504:518 secretor status 504:518 Their glycosylation is associated with blood group and secretor status, and represents a reservoir of potential disease biomarkers. 27610614 5 40 theme mouth 656:660 arg1 saliva 662:667 whole human mouth saliva 644:667 whole human mouth saliva collected 3 times a day from a healthy individual over a 5 days period 644:738 This study aims to analyse and compare O-glycans released from whole human mouth saliva collected 3 times a day from a healthy individual over a 5 days period. 27610614 6 41 theme performance 845:855 arg1 chromatography 864:877 ultra-high performance liquid chromatography 834:877 ultra-high performance liquid chromatography with fluorescence detection (UHPLC-FLR) coupled to electrospray ionization mass spectrometry (ESI-MS/MS) 834:982 O-linked glycans were released by hydrazinolysis, labelled with procainamide and analysed by ultra-high performance liquid chromatography with fluorescence detection (UHPLC-FLR) coupled to electrospray ionization mass spectrometry (ESI-MS/MS). 27610614 7 42 theme preparation 996:1006 arg1 method 1008:1013 The sample preparation method 985:1013 The sample preparation method 985:1013 The sample preparation method showed excellent reproducibility and can therefore be used for biomarker discovery. 27610614 3 43 from saliva 441:446 arg1 abundant 423:430 abundant 423:430 abundant 423:430 Mucins, which are highly O-glycosylated proteins, are particularly abundant in human saliva. 27610614 9 44 from changes 1232:1238 arg1 concentrations 1256:1269 the salivary concentrations 1243:1269 the salivary concentrations of specific proteins 1243:1290 These changes may be related to changes in the salivary concentrations of specific proteins. 27610614 9 45 theme specific 1274:1281 arg1 proteins 1283:1290 specific proteins 1274:1290 specific proteins 1274:1290 These changes may be related to changes in the salivary concentrations of specific proteins. 27610614 5 46 attach released 630:637 arg2 O-glycans 620:628 O-glycans 620:628 O-glycans released from whole human mouth saliva collected 3 times a day from a healthy individual over a 5 days period 620:738 This study aims to analyse and compare O-glycans released from whole human mouth saliva collected 3 times a day from a healthy individual over a 5 days period. 27610614 5 46 attach released 630:637 arg1 saliva 662:667 whole human mouth saliva 644:667 whole human mouth saliva collected 3 times a day from a healthy individual over a 5 days period 644:738 This study aims to analyse and compare O-glycans released from whole human mouth saliva collected 3 times a day from a healthy individual over a 5 days period. 27610614 1 47 theme non-invasive 197:208 arg1 collection 210:219 non-invasive collection 197:219 non-invasive collection of saliva 197:229 The study of saliva O-glycosylation is receiving increasing attention due to the potential of glycans for disease biomarkers, but also due to easy access and non-invasive collection of saliva as biological fluid. 27610614 9 48 theme proteins 1283:1290 arg1 concentrations 1256:1269 the salivary concentrations 1243:1269 the salivary concentrations of specific proteins 1243:1290 These changes may be related to changes in the salivary concentrations of specific proteins. 27610614 8 49 theme human 1149:1153 arg1 saliva 1155:1160 human saliva 1149:1160 human saliva 1149:1160 Our data demonstrates that the O-glycosylation in human saliva changes significantly during the day. 27610614 7 50 theme sample 989:994 arg1 method 1008:1013 The sample preparation method 985:1013 The sample preparation method 985:1013 The sample preparation method showed excellent reproducibility and can therefore be used for biomarker discovery. 27610614 1 51 theme glycans 133:139 arg1 potential 120:128 the potential 116:128 the potential of glycans for disease biomarkers 116:162 The study of saliva O-glycosylation is receiving increasing attention due to the potential of glycans for disease biomarkers, but also due to easy access and non-invasive collection of saliva as biological fluid. 27610614 2 52 from rich 262:265 arg1 glycoproteins 270:282 glycoproteins 270:282 glycoproteins which are secreted from the bloodstream or produced by salivary glands 270:353 Saliva is rich in glycoproteins which are secreted from the bloodstream or produced by salivary glands. 27610614 4 53 theme blood 488:492 arg1 group 494:498 blood group 488:498 blood group 488:498 Their glycosylation is associated with blood group and secretor status, and represents a reservoir of potential disease biomarkers. 27610614 2 54 theme salivary 339:346 arg1 glands 348:353 salivary glands 339:353 salivary glands 339:353 Saliva is rich in glycoproteins which are secreted from the bloodstream or produced by salivary glands. 27610614 6 55 theme electrospray 930:941 arg1 spectrometry 959:970 electrospray ionization mass spectrometry 930:970 electrospray ionization mass spectrometry (ESI-MS/MS) 930:982 O-linked glycans were released by hydrazinolysis, labelled with procainamide and analysed by ultra-high performance liquid chromatography with fluorescence detection (UHPLC-FLR) coupled to electrospray ionization mass spectrometry (ESI-MS/MS). 27610614 6 55 theme electrospray 930:941 arg1 ESI-MS/MS 973:981 ESI-MS/MS 973:981 ESI-MS/MS 973:981 O-linked glycans were released by hydrazinolysis, labelled with procainamide and analysed by ultra-high performance liquid chromatography with fluorescence detection (UHPLC-FLR) coupled to electrospray ionization mass spectrometry (ESI-MS/MS). 27610614 1 56 theme saliva 224:229 arg1 access 186:191 easy access 181:191 easy access 181:191 The study of saliva O-glycosylation is receiving increasing attention due to the potential of glycans for disease biomarkers, but also due to easy access and non-invasive collection of saliva as biological fluid. 27610614 1 56 theme saliva 224:229 arg1 collection 210:219 non-invasive collection 197:219 non-invasive collection of saliva 197:229 The study of saliva O-glycosylation is receiving increasing attention due to the potential of glycans for disease biomarkers, but also due to easy access and non-invasive collection of saliva as biological fluid. 27311888 0 0 theme Transporter 89:99 arg1 Glucosamine 115:125 Glucose Transporter 2-Transported Glucosamine 81:125 Glucose Transporter 2-Transported Glucosamine 81:125 Embryonic Stem Cell Proliferation Stimulated By Altered Anabolic Metabolism From Glucose Transporter 2-Transported Glucosamine. 27311888 3 1 theme functional 661:670 arg1 transporters 678:689 functional GLUT2 transporters 661:689 functional GLUT2 transporters 661:689 To understand this, we employed a novel murine embryonic stem cell (ESC) line that, like mouse embryos, expresses functional GLUT2 transporters. 27311888 2 2 theme sugar 328:332 arg1 GlcN 347:350 GlcN 347:350 GlcN 347:350 GLUT2 can transport the amino sugar glucosamine (GlcN), which could increase substrate for the hexosamine biosynthetic pathway (HBSP) that produces UDP-N-acetylglucosamine for O-linked N-acetylglucosamine modification (O-GlcNAcylation) of proteins. 27311888 2 2 theme sugar 328:332 arg1 glucosamine 334:344 the amino sugar glucosamine 318:344 the amino sugar glucosamine (GlcN) 318:351 GLUT2 can transport the amino sugar glucosamine (GlcN), which could increase substrate for the hexosamine biosynthetic pathway (HBSP) that produces UDP-N-acetylglucosamine for O-linked N-acetylglucosamine modification (O-GlcNAcylation) of proteins. 27311888 1 3 theme embryonic 238:246 arg1 day 248:250 embryonic day 10.5 238:255 embryonic day 10.5 238:255 The hexose transporter, GLUT2 (SLC2A2), which is expressed by mouse embryos, is important for survival before embryonic day 10.5, but its function in embryos is unknown. 27311888 0 4 theme Glucose 81:87 arg1 Glucosamine 115:125 Glucose Transporter 2-Transported Glucosamine 81:125 Glucose Transporter 2-Transported Glucosamine 81:125 Embryonic Stem Cell Proliferation Stimulated By Altered Anabolic Metabolism From Glucose Transporter 2-Transported Glucosamine. 27311888 7 5 theme glycolytic- 955:965 arg1 intermediates 989:1001 glycolytic- and glutamine-derived intermediates 955:1001 glycolytic- and glutamine-derived intermediates that are needed for anabolic metabolism 955:1041 Consequently, glycolytic- and glutamine-derived intermediates that are needed for anabolic metabolism were increased. 27311888 2 6 theme amino 322:326 arg1 GlcN 347:350 GlcN 347:350 GlcN 347:350 GLUT2 can transport the amino sugar glucosamine (GlcN), which could increase substrate for the hexosamine biosynthetic pathway (HBSP) that produces UDP-N-acetylglucosamine for O-linked N-acetylglucosamine modification (O-GlcNAcylation) of proteins. 27311888 2 6 theme amino 322:326 arg1 glucosamine 334:344 the amino sugar glucosamine 318:344 the amino sugar glucosamine (GlcN) 318:351 GLUT2 can transport the amino sugar glucosamine (GlcN), which could increase substrate for the hexosamine biosynthetic pathway (HBSP) that produces UDP-N-acetylglucosamine for O-linked N-acetylglucosamine modification (O-GlcNAcylation) of proteins. 27311888 4 7 theme GLUT2-dependent 731:745 arg1 fashion 747:753 a GLUT2-dependent fashion 729:753 a GLUT2-dependent fashion 729:753 GlcN stimulated ESC proliferation in a GLUT2-dependent fashion but did not regulate pluripotency. 27311888 0 8 theme 2-Transported 101:113 arg1 Glucosamine 115:125 Glucose Transporter 2-Transported Glucosamine 81:125 Glucose Transporter 2-Transported Glucosamine 81:125 Embryonic Stem Cell Proliferation Stimulated By Altered Anabolic Metabolism From Glucose Transporter 2-Transported Glucosamine. 27311888 6 9 from dependence 885:894 arg1 glutamine 930:938 glutamine 930:938 glutamine 930:938 Instead, GlcN decreased dependence of the HBSP on fructose-6-PO4 and glutamine. 27311888 6 9 from dependence 885:894 arg1 fructose-6-PO4 911:924 fructose-6-PO4 911:924 fructose-6-PO4 911:924 Instead, GlcN decreased dependence of the HBSP on fructose-6-PO4 and glutamine. 27311888 1 10 from function 266:273 arg1 embryos 278:284 embryos 278:284 embryos 278:284 The hexose transporter, GLUT2 (SLC2A2), which is expressed by mouse embryos, is important for survival before embryonic day 10.5, but its function in embryos is unknown. 27311888 5 11 theme increased 834:842 arg1 O-GlcNAcylation 844:858 increased O-GlcNAcylation 834:858 increased O-GlcNAcylation 834:858 Stimulation of proliferation was not due to increased O-GlcNAcylation. 27311888 8 12 theme GLUT2-expressing 1178:1193 arg1 ESC 1195:1197 GLUT2-expressing ESC 1178:1197 GLUT2-expressing ESC 1178:1197 Thus, maternally obtained GlcN may increase substrates for biomass accumulation by embryos, as exogenous GlcN does for GLUT2-expressing ESC, and may explain the need for GLUT2 expression by embryos. 27311888 3 13 theme GLUT2 672:676 arg1 transporters 678:689 functional GLUT2 transporters 661:689 functional GLUT2 transporters 661:689 To understand this, we employed a novel murine embryonic stem cell (ESC) line that, like mouse embryos, expresses functional GLUT2 transporters. 27311888 0 14 theme Embryonic 0:8 arg1 Proliferation 20:32 Embryonic Stem Cell Proliferation 0:32 Embryonic Stem Cell Proliferation 0:32 Embryonic Stem Cell Proliferation Stimulated By Altered Anabolic Metabolism From Glucose Transporter 2-Transported Glucosamine. 27311888 0 15 theme Stem 10:13 arg1 Proliferation 20:32 Embryonic Stem Cell Proliferation 0:32 Embryonic Stem Cell Proliferation 0:32 Embryonic Stem Cell Proliferation Stimulated By Altered Anabolic Metabolism From Glucose Transporter 2-Transported Glucosamine. 27311888 8 16 theme exogenous 1154:1162 arg1 GlcN 1164:1167 exogenous GlcN 1154:1167 exogenous GlcN 1154:1167 Thus, maternally obtained GlcN may increase substrates for biomass accumulation by embryos, as exogenous GlcN does for GLUT2-expressing ESC, and may explain the need for GLUT2 expression by embryos. 27311888 4 17 theme ESC 708:710 arg1 proliferation 712:724 ESC proliferation 708:724 ESC proliferation 708:724 GlcN stimulated ESC proliferation in a GLUT2-dependent fashion but did not regulate pluripotency. 27311888 2 18 theme biosynthetic 404:415 arg1 HBSP 426:429 HBSP 426:429 HBSP 426:429 GLUT2 can transport the amino sugar glucosamine (GlcN), which could increase substrate for the hexosamine biosynthetic pathway (HBSP) that produces UDP-N-acetylglucosamine for O-linked N-acetylglucosamine modification (O-GlcNAcylation) of proteins. 27311888 2 18 theme biosynthetic 404:415 arg1 pathway 417:423 the hexosamine biosynthetic pathway 389:423 the hexosamine biosynthetic pathway (HBSP) that produces UDP-N-acetylglucosamine for O-linked N-acetylglucosamine modification (O-GlcNAcylation) of proteins 389:544 GLUT2 can transport the amino sugar glucosamine (GlcN), which could increase substrate for the hexosamine biosynthetic pathway (HBSP) that produces UDP-N-acetylglucosamine for O-linked N-acetylglucosamine modification (O-GlcNAcylation) of proteins. 27311888 7 19 link glutamine-derived 971:987 arg1 intermediates 989:1001 glycolytic- and glutamine-derived intermediates 955:1001 glycolytic- and glutamine-derived intermediates that are needed for anabolic metabolism 955:1041 Consequently, glycolytic- and glutamine-derived intermediates that are needed for anabolic metabolism were increased. 27311888 8 20 theme obtained 1076:1083 arg1 GlcN 1085:1088 maternally obtained GlcN 1065:1088 maternally obtained GlcN 1065:1088 Thus, maternally obtained GlcN may increase substrates for biomass accumulation by embryos, as exogenous GlcN does for GLUT2-expressing ESC, and may explain the need for GLUT2 expression by embryos. 27311888 2 21 theme hexosamine 393:402 arg1 HBSP 426:429 HBSP 426:429 HBSP 426:429 GLUT2 can transport the amino sugar glucosamine (GlcN), which could increase substrate for the hexosamine biosynthetic pathway (HBSP) that produces UDP-N-acetylglucosamine for O-linked N-acetylglucosamine modification (O-GlcNAcylation) of proteins. 27311888 2 21 theme hexosamine 393:402 arg1 pathway 417:423 the hexosamine biosynthetic pathway 389:423 the hexosamine biosynthetic pathway (HBSP) that produces UDP-N-acetylglucosamine for O-linked N-acetylglucosamine modification (O-GlcNAcylation) of proteins 389:544 GLUT2 can transport the amino sugar glucosamine (GlcN), which could increase substrate for the hexosamine biosynthetic pathway (HBSP) that produces UDP-N-acetylglucosamine for O-linked N-acetylglucosamine modification (O-GlcNAcylation) of proteins. 27311888 1 22 theme mouse 190:194 arg1 embryos 196:202 mouse embryos 190:202 mouse embryos 190:202 The hexose transporter, GLUT2 (SLC2A2), which is expressed by mouse embryos, is important for survival before embryonic day 10.5, but its function in embryos is unknown. 27311888 0 23 theme Cell 15:18 arg1 Proliferation 20:32 Embryonic Stem Cell Proliferation 0:32 Embryonic Stem Cell Proliferation 0:32 Embryonic Stem Cell Proliferation Stimulated By Altered Anabolic Metabolism From Glucose Transporter 2-Transported Glucosamine. 27311888 2 24 dep N-acetylglucosamine 483:501 arg1 modification 503:514 modification 503:514 O-linked N-acetylglucosamine modification (O-GlcNAcylation) of proteins 474:544 GLUT2 can transport the amino sugar glucosamine (GlcN), which could increase substrate for the hexosamine biosynthetic pathway (HBSP) that produces UDP-N-acetylglucosamine for O-linked N-acetylglucosamine modification (O-GlcNAcylation) of proteins. 27311888 6 25 theme HBSP 903:906 arg1 dependence 885:894 dependence 885:894 dependence of the HBSP on fructose-6-PO4 and glutamine 885:938 Instead, GlcN decreased dependence of the HBSP on fructose-6-PO4 and glutamine. 27311888 3 26 theme novel 581:585 arg1 line 620:623 a novel murine embryonic stem cell (ESC) line 579:623 a novel murine embryonic stem cell (ESC) line that, like mouse embryos, expresses functional GLUT2 transporters 579:689 To understand this, we employed a novel murine embryonic stem cell (ESC) line that, like mouse embryos, expresses functional GLUT2 transporters. 27311888 7 27 theme anabolic 1023:1030 arg1 metabolism 1032:1041 anabolic metabolism 1023:1041 anabolic metabolism 1023:1041 Consequently, glycolytic- and glutamine-derived intermediates that are needed for anabolic metabolism were increased. 27311888 0 28 theme Anabolic 56:63 arg1 Metabolism 65:74 Altered Anabolic Metabolism 48:74 Altered Anabolic Metabolism From Glucose Transporter 2-Transported Glucosamine 48:125 Embryonic Stem Cell Proliferation Stimulated By Altered Anabolic Metabolism From Glucose Transporter 2-Transported Glucosamine. 27311888 5 29 theme proliferation 805:817 arg1 Stimulation 790:800 Stimulation 790:800 Stimulation of proliferation 790:817 Stimulation of proliferation was not due to increased O-GlcNAcylation. 27311888 1 30 theme hexose 132:137 arg1 important 208:216 important 208:216 important 208:216 The hexose transporter, GLUT2 (SLC2A2), which is expressed by mouse embryos, is important for survival before embryonic day 10.5, but its function in embryos is unknown. 27311888 1 30 theme hexose 132:137 arg1 GLUT2 152:156 GLUT2 152:156 GLUT2 (SLC2A2) 152:165 The hexose transporter, GLUT2 (SLC2A2), which is expressed by mouse embryos, is important for survival before embryonic day 10.5, but its function in embryos is unknown. 27311888 1 30 theme hexose 132:137 arg1 transporter 139:149 The hexose transporter 128:149 The hexose transporter 128:149 The hexose transporter, GLUT2 (SLC2A2), which is expressed by mouse embryos, is important for survival before embryonic day 10.5, but its function in embryos is unknown. 27311888 0 31 theme Altered 48:54 arg1 Metabolism 65:74 Altered Anabolic Metabolism 48:74 Altered Anabolic Metabolism From Glucose Transporter 2-Transported Glucosamine 48:125 Embryonic Stem Cell Proliferation Stimulated By Altered Anabolic Metabolism From Glucose Transporter 2-Transported Glucosamine. 27311888 8 32 theme biomass 1118:1124 arg1 accumulation 1126:1137 biomass accumulation 1118:1137 biomass accumulation by embryos 1118:1148 Thus, maternally obtained GlcN may increase substrates for biomass accumulation by embryos, as exogenous GlcN does for GLUT2-expressing ESC, and may explain the need for GLUT2 expression by embryos. 27311888 2 33 link O-linked 474:481 arg1 N-acetylglucosamine 483:501 O-linked N-acetylglucosamine 474:501 O-linked N-acetylglucosamine modification (O-GlcNAcylation) of proteins 474:544 GLUT2 can transport the amino sugar glucosamine (GlcN), which could increase substrate for the hexosamine biosynthetic pathway (HBSP) that produces UDP-N-acetylglucosamine for O-linked N-acetylglucosamine modification (O-GlcNAcylation) of proteins. 27311888 2 33 link O-linked 474:481 arg1 O-GlcNAcylation 517:531 O-GlcNAcylation 517:531 O-GlcNAcylation 517:531 GLUT2 can transport the amino sugar glucosamine (GlcN), which could increase substrate for the hexosamine biosynthetic pathway (HBSP) that produces UDP-N-acetylglucosamine for O-linked N-acetylglucosamine modification (O-GlcNAcylation) of proteins. 27311888 3 34 theme mouse 636:640 arg1 embryos 642:648 mouse embryos 636:648 mouse embryos 636:648 To understand this, we employed a novel murine embryonic stem cell (ESC) line that, like mouse embryos, expresses functional GLUT2 transporters. 27311888 3 35 theme stem 604:607 arg1 ESC 615:617 ESC 615:617 ESC 615:617 To understand this, we employed a novel murine embryonic stem cell (ESC) line that, like mouse embryos, expresses functional GLUT2 transporters. 27311888 3 35 theme stem 604:607 arg1 cell 609:612 embryonic stem cell 594:612 a novel murine embryonic stem cell (ESC) line that, like mouse embryos, expresses functional GLUT2 transporters 579:689 To understand this, we employed a novel murine embryonic stem cell (ESC) line that, like mouse embryos, expresses functional GLUT2 transporters. 27311888 0 36 from Glucosamine 115:125 arg1 Metabolism 65:74 Altered Anabolic Metabolism 48:74 Altered Anabolic Metabolism From Glucose Transporter 2-Transported Glucosamine 48:125 Embryonic Stem Cell Proliferation Stimulated By Altered Anabolic Metabolism From Glucose Transporter 2-Transported Glucosamine. 27311888 3 37 theme cell 609:612 arg1 line 620:623 a novel murine embryonic stem cell (ESC) line 579:623 a novel murine embryonic stem cell (ESC) line that, like mouse embryos, expresses functional GLUT2 transporters 579:689 To understand this, we employed a novel murine embryonic stem cell (ESC) line that, like mouse embryos, expresses functional GLUT2 transporters. 27311888 2 38 theme O-linked 474:481 arg1 N-acetylglucosamine 483:501 O-linked N-acetylglucosamine 474:501 O-linked N-acetylglucosamine modification (O-GlcNAcylation) of proteins 474:544 GLUT2 can transport the amino sugar glucosamine (GlcN), which could increase substrate for the hexosamine biosynthetic pathway (HBSP) that produces UDP-N-acetylglucosamine for O-linked N-acetylglucosamine modification (O-GlcNAcylation) of proteins. 27311888 2 38 theme O-linked 474:481 arg1 O-GlcNAcylation 517:531 O-GlcNAcylation 517:531 O-GlcNAcylation 517:531 GLUT2 can transport the amino sugar glucosamine (GlcN), which could increase substrate for the hexosamine biosynthetic pathway (HBSP) that produces UDP-N-acetylglucosamine for O-linked N-acetylglucosamine modification (O-GlcNAcylation) of proteins. 27311888 3 39 theme murine 587:592 arg1 line 620:623 a novel murine embryonic stem cell (ESC) line 579:623 a novel murine embryonic stem cell (ESC) line that, like mouse embryos, expresses functional GLUT2 transporters 579:689 To understand this, we employed a novel murine embryonic stem cell (ESC) line that, like mouse embryos, expresses functional GLUT2 transporters. 27311888 2 40 theme proteins 537:544 arg1 N-acetylglucosamine 483:501 O-linked N-acetylglucosamine 474:501 O-linked N-acetylglucosamine modification (O-GlcNAcylation) of proteins 474:544 GLUT2 can transport the amino sugar glucosamine (GlcN), which could increase substrate for the hexosamine biosynthetic pathway (HBSP) that produces UDP-N-acetylglucosamine for O-linked N-acetylglucosamine modification (O-GlcNAcylation) of proteins. 27311888 2 40 theme proteins 537:544 arg1 O-GlcNAcylation 517:531 O-GlcNAcylation 517:531 O-GlcNAcylation 517:531 GLUT2 can transport the amino sugar glucosamine (GlcN), which could increase substrate for the hexosamine biosynthetic pathway (HBSP) that produces UDP-N-acetylglucosamine for O-linked N-acetylglucosamine modification (O-GlcNAcylation) of proteins. 27311888 8 41 theme GLUT2 1229:1233 arg1 expression 1235:1244 GLUT2 expression 1229:1244 GLUT2 expression by embryos 1229:1255 Thus, maternally obtained GlcN may increase substrates for biomass accumulation by embryos, as exogenous GlcN does for GLUT2-expressing ESC, and may explain the need for GLUT2 expression by embryos. 27311888 3 42 theme embryonic 594:602 arg1 ESC 615:617 ESC 615:617 ESC 615:617 To understand this, we employed a novel murine embryonic stem cell (ESC) line that, like mouse embryos, expresses functional GLUT2 transporters. 27311888 3 42 theme embryonic 594:602 arg1 cell 609:612 embryonic stem cell 594:612 a novel murine embryonic stem cell (ESC) line that, like mouse embryos, expresses functional GLUT2 transporters 579:689 To understand this, we employed a novel murine embryonic stem cell (ESC) line that, like mouse embryos, expresses functional GLUT2 transporters. 27311888 7 43 theme glutamine-derived 971:987 arg1 intermediates 989:1001 glycolytic- and glutamine-derived intermediates 955:1001 glycolytic- and glutamine-derived intermediates that are needed for anabolic metabolism 955:1041 Consequently, glycolytic- and glutamine-derived intermediates that are needed for anabolic metabolism were increased. 25842315 5 0 dep arabinose 685:693 arg1 2-O-linked 736:745 2-O-linked 736:745 2-O-linked 736:745 There are residues of mannose, the arabinose, pyranose predominantly, is terminal and 2-O-linked. 25842315 5 0 dep arabinose 685:693 arg1 terminal 723:730 terminal 723:730 terminal 723:730 There are residues of mannose, the arabinose, pyranose predominantly, is terminal and 2-O-linked. 25842315 3 1 dep A. 255:256 arg1 tortuosa 258:265 tortuosa 258:265 tortuosa 258:265 The elucidation of the A. tortuosa gum structure by the combination of classical chemical methods, size exclusion chromatography and NMR spectroscopy, was the objective of this investigation. 25842315 4 2 theme type 499:502 arg1 II 504:505 an arabinogalactan type II 480:505 an arabinogalactan type II 480:505 The data obtained show that the heteropolysaccharide is an arabinogalactan type II, highly ramified, with lateral chains at C-2 as well as at C-6 of the galactose 3-O residues; mono-O-substituted galactoses were not detected. 25842315 4 2 theme type 499:502 arg1 heteropolysaccharide 456:475 the heteropolysaccharide 452:475 the heteropolysaccharide 452:475 The data obtained show that the heteropolysaccharide is an arabinogalactan type II, highly ramified, with lateral chains at C-2 as well as at C-6 of the galactose 3-O residues; mono-O-substituted galactoses were not detected. 25842315 7 3 theme Yariv 946:950 arg1 reagent 952:958 β-glucosyl Yariv reagent 935:958 β-glucosyl Yariv reagent 935:958 The proteic fraction is probably represented by an arabinogalactan-protein complex that binds poorly with β-glucosyl Yariv reagent, and two glycoproteins. 25842315 7 4 theme proteic 833:839 arg1 fraction 841:848 The proteic fraction 829:848 The proteic fraction 829:848 The proteic fraction is probably represented by an arabinogalactan-protein complex that binds poorly with β-glucosyl Yariv reagent, and two glycoproteins. 25842315 4 5 theme arabinogalactan 483:497 arg1 II 504:505 an arabinogalactan type II 480:505 an arabinogalactan type II 480:505 The data obtained show that the heteropolysaccharide is an arabinogalactan type II, highly ramified, with lateral chains at C-2 as well as at C-6 of the galactose 3-O residues; mono-O-substituted galactoses were not detected. 25842315 4 5 theme arabinogalactan 483:497 arg1 heteropolysaccharide 456:475 the heteropolysaccharide 452:475 the heteropolysaccharide 452:475 The data obtained show that the heteropolysaccharide is an arabinogalactan type II, highly ramified, with lateral chains at C-2 as well as at C-6 of the galactose 3-O residues; mono-O-substituted galactoses were not detected. 25842315 3 6 theme size 331:334 arg1 methods 322:328 classical chemical methods 303:328 classical chemical methods 303:328 The elucidation of the A. tortuosa gum structure by the combination of classical chemical methods, size exclusion chromatography and NMR spectroscopy, was the objective of this investigation. 25842315 3 6 theme size 331:334 arg1 chromatography 346:359 size exclusion chromatography 331:359 size exclusion chromatography 331:359 The elucidation of the A. tortuosa gum structure by the combination of classical chemical methods, size exclusion chromatography and NMR spectroscopy, was the objective of this investigation. 25842315 1 7 theme Acacia 56:61 arg1 tortuosa 63:70 Acacia tortuosa 56:70 Acacia tortuosa 56:70 Acacia tortuosa produces a clear gum, very soluble in water. 25842315 3 8 theme chemical 313:320 arg1 methods 322:328 classical chemical methods 303:328 classical chemical methods 303:328 The elucidation of the A. tortuosa gum structure by the combination of classical chemical methods, size exclusion chromatography and NMR spectroscopy, was the objective of this investigation. 25842315 3 8 theme chemical 313:320 arg1 chromatography 346:359 size exclusion chromatography 331:359 size exclusion chromatography 331:359 The elucidation of the A. tortuosa gum structure by the combination of classical chemical methods, size exclusion chromatography and NMR spectroscopy, was the objective of this investigation. 25842315 3 8 theme chemical 313:320 arg1 spectroscopy 369:380 NMR spectroscopy 365:380 NMR spectroscopy 365:380 The elucidation of the A. tortuosa gum structure by the combination of classical chemical methods, size exclusion chromatography and NMR spectroscopy, was the objective of this investigation. 25842315 7 9 theme β-glucosyl 935:944 arg1 reagent 952:958 β-glucosyl Yariv reagent 935:958 β-glucosyl Yariv reagent 935:958 The proteic fraction is probably represented by an arabinogalactan-protein complex that binds poorly with β-glucosyl Yariv reagent, and two glycoproteins. 25842315 4 10 theme mono-O-substituted 601:618 arg1 galactoses 620:629 mono-O-substituted galactoses 601:629 mono-O-substituted galactoses 601:629 The data obtained show that the heteropolysaccharide is an arabinogalactan type II, highly ramified, with lateral chains at C-2 as well as at C-6 of the galactose 3-O residues; mono-O-substituted galactoses were not detected. 25842315 3 11 theme methods 322:328 arg1 combination 288:298 the combination 284:298 the combination of classical chemical methods, size exclusion chromatography and NMR spectroscopy, 284:381 The elucidation of the A. tortuosa gum structure by the combination of classical chemical methods, size exclusion chromatography and NMR spectroscopy, was the objective of this investigation. 25842315 2 12 theme Previous 117:124 arg1 reports 126:132 Previous reports 117:132 Previous reports 117:132 Previous reports showed that it was constituted by four fractions, one of them an arabinogalactan-protein complex. 25842315 0 13 theme New 0:2 arg1 features 15:22 New structural features 0:22 New structural features of Acacia tortuosa gum exudate. 0:54 New structural features of Acacia tortuosa gum exudate. 25842315 3 14 theme investigation 409:421 arg1 objective 391:399 the objective 387:399 the objective of this investigation 387:421 The elucidation of the A. tortuosa gum structure by the combination of classical chemical methods, size exclusion chromatography and NMR spectroscopy, was the objective of this investigation. 25842315 3 14 theme investigation 409:421 arg1 elucidation 236:246 The elucidation 232:246 The elucidation of the A. tortuosa gum structure by the combination of classical chemical methods, size exclusion chromatography and NMR spectroscopy, 232:381 The elucidation of the A. tortuosa gum structure by the combination of classical chemical methods, size exclusion chromatography and NMR spectroscopy, was the objective of this investigation. 25842315 0 15 theme structural 4:13 arg1 features 15:22 New structural features 0:22 New structural features of Acacia tortuosa gum exudate. 0:54 New structural features of Acacia tortuosa gum exudate. 25842315 1 16 from water 110:114 arg1 soluble 99:105 soluble 99:105 soluble 99:105 Acacia tortuosa produces a clear gum, very soluble in water. 25842315 3 17 theme NMR 365:367 arg1 methods 322:328 classical chemical methods 303:328 classical chemical methods 303:328 The elucidation of the A. tortuosa gum structure by the combination of classical chemical methods, size exclusion chromatography and NMR spectroscopy, was the objective of this investigation. 25842315 3 17 theme NMR 365:367 arg1 spectroscopy 369:380 NMR spectroscopy 365:380 NMR spectroscopy 365:380 The elucidation of the A. tortuosa gum structure by the combination of classical chemical methods, size exclusion chromatography and NMR spectroscopy, was the objective of this investigation. 25842315 7 18 gly glycoproteins 969:981 arg1 glycoproteins 969:981 two glycoproteins 965:981 two glycoproteins 965:981 The proteic fraction is probably represented by an arabinogalactan-protein complex that binds poorly with β-glucosyl Yariv reagent, and two glycoproteins. 25842315 1 19 theme clear 83:87 arg1 gum 89:91 a clear gum 81:91 a clear gum 81:91 Acacia tortuosa produces a clear gum, very soluble in water. 25842315 3 20 theme exclusion 336:344 arg1 methods 322:328 classical chemical methods 303:328 classical chemical methods 303:328 The elucidation of the A. tortuosa gum structure by the combination of classical chemical methods, size exclusion chromatography and NMR spectroscopy, was the objective of this investigation. 25842315 3 20 theme exclusion 336:344 arg1 chromatography 346:359 size exclusion chromatography 331:359 size exclusion chromatography 331:359 The elucidation of the A. tortuosa gum structure by the combination of classical chemical methods, size exclusion chromatography and NMR spectroscopy, was the objective of this investigation. 25842315 1 21 from soluble 99:105 arg1 water 110:114 water 110:114 water 110:114 Acacia tortuosa produces a clear gum, very soluble in water. 25842315 4 22 theme galactose 577:585 arg1 residues 591:598 the galactose 3-O residues 573:598 the galactose 3-O residues 573:598 The data obtained show that the heteropolysaccharide is an arabinogalactan type II, highly ramified, with lateral chains at C-2 as well as at C-6 of the galactose 3-O residues; mono-O-substituted galactoses were not detected. 25842315 3 23 theme A. 255:256 arg1 structure 271:279 the A. tortuosa gum structure 251:279 the A. tortuosa gum structure 251:279 The elucidation of the A. tortuosa gum structure by the combination of classical chemical methods, size exclusion chromatography and NMR spectroscopy, was the objective of this investigation. 25842315 4 24 with II 504:505 arg1 chains 538:543 lateral chains 530:543 lateral chains at C-2 530:550 The data obtained show that the heteropolysaccharide is an arabinogalactan type II, highly ramified, with lateral chains at C-2 as well as at C-6 of the galactose 3-O residues; mono-O-substituted galactoses were not detected. 25842315 2 25 dep one 184:186 arg1 complex 223:229 an arabinogalactan-protein complex 196:229 one of them an arabinogalactan-protein complex 184:229 Previous reports showed that it was constituted by four fractions, one of them an arabinogalactan-protein complex. 25842315 0 26 theme tortuosa 34:41 arg1 exudate 47:53 Acacia tortuosa gum exudate 27:53 Acacia tortuosa gum exudate 27:53 New structural features of Acacia tortuosa gum exudate. 25842315 4 27 theme lateral 530:536 arg1 chains 538:543 lateral chains 530:543 lateral chains at C-2 530:550 The data obtained show that the heteropolysaccharide is an arabinogalactan type II, highly ramified, with lateral chains at C-2 as well as at C-6 of the galactose 3-O residues; mono-O-substituted galactoses were not detected. 25842315 4 28 theme residues 591:598 arg1 C-6 566:568 C-6 566:568 C-6 of the galactose 3-O residues 566:598 The data obtained show that the heteropolysaccharide is an arabinogalactan type II, highly ramified, with lateral chains at C-2 as well as at C-6 of the galactose 3-O residues; mono-O-substituted galactoses were not detected. 25842315 0 29 theme Acacia 27:32 arg1 exudate 47:53 Acacia tortuosa gum exudate 27:53 Acacia tortuosa gum exudate 27:53 New structural features of Acacia tortuosa gum exudate. 25842315 5 30 theme mannose 672:678 arg1 residues 660:667 residues 660:667 residues of mannose, the arabinose, pyranose predominantly, is terminal and 2-O-linked 660:745 There are residues of mannose, the arabinose, pyranose predominantly, is terminal and 2-O-linked. 25842315 5 30 theme mannose 672:678 arg1 mannose 672:678 mannose 672:678 mannose 672:678 There are residues of mannose, the arabinose, pyranose predominantly, is terminal and 2-O-linked. 25842315 2 31 theme them 191:194 arg1 them 191:194 them 191:194 them 191:194 Previous reports showed that it was constituted by four fractions, one of them an arabinogalactan-protein complex. 25842315 2 31 theme them 191:194 arg1 one 184:186 one 184:186 one 184:186 Previous reports showed that it was constituted by four fractions, one of them an arabinogalactan-protein complex. 25842315 2 31 theme them 191:194 arg1 fractions 173:181 four fractions 168:181 four fractions 168:181 Previous reports showed that it was constituted by four fractions, one of them an arabinogalactan-protein complex. 25842315 4 32 theme 3-O 587:589 arg1 residues 591:598 the galactose 3-O residues 573:598 the galactose 3-O residues 573:598 The data obtained show that the heteropolysaccharide is an arabinogalactan type II, highly ramified, with lateral chains at C-2 as well as at C-6 of the galactose 3-O residues; mono-O-substituted galactoses were not detected. 25842315 0 33 theme exudate 47:53 arg1 features 15:22 New structural features 0:22 New structural features of Acacia tortuosa gum exudate. 0:54 New structural features of Acacia tortuosa gum exudate. 25842315 3 34 theme structure 271:279 arg1 elucidation 236:246 The elucidation 232:246 The elucidation of the A. tortuosa gum structure by the combination of classical chemical methods, size exclusion chromatography and NMR spectroscopy, 232:381 The elucidation of the A. tortuosa gum structure by the combination of classical chemical methods, size exclusion chromatography and NMR spectroscopy, was the objective of this investigation. 25842315 3 34 theme structure 271:279 arg1 objective 391:399 the objective 387:399 the objective of this investigation 387:421 The elucidation of the A. tortuosa gum structure by the combination of classical chemical methods, size exclusion chromatography and NMR spectroscopy, was the objective of this investigation. 25842315 4 35 from C-6 566:568 arg1 II 504:505 an arabinogalactan type II 480:505 an arabinogalactan type II 480:505 The data obtained show that the heteropolysaccharide is an arabinogalactan type II, highly ramified, with lateral chains at C-2 as well as at C-6 of the galactose 3-O residues; mono-O-substituted galactoses were not detected. 25842315 4 35 from C-6 566:568 arg1 heteropolysaccharide 456:475 the heteropolysaccharide 452:475 the heteropolysaccharide 452:475 The data obtained show that the heteropolysaccharide is an arabinogalactan type II, highly ramified, with lateral chains at C-2 as well as at C-6 of the galactose 3-O residues; mono-O-substituted galactoses were not detected. 25842315 0 36 theme gum 43:45 arg1 exudate 47:53 Acacia tortuosa gum exudate 27:53 Acacia tortuosa gum exudate 27:53 New structural features of Acacia tortuosa gum exudate. 25842315 4 37 theme ramified 515:522 arg1 II 504:505 an arabinogalactan type II 480:505 an arabinogalactan type II 480:505 The data obtained show that the heteropolysaccharide is an arabinogalactan type II, highly ramified, with lateral chains at C-2 as well as at C-6 of the galactose 3-O residues; mono-O-substituted galactoses were not detected. 25842315 4 37 theme ramified 515:522 arg1 heteropolysaccharide 456:475 the heteropolysaccharide 452:475 the heteropolysaccharide 452:475 The data obtained show that the heteropolysaccharide is an arabinogalactan type II, highly ramified, with lateral chains at C-2 as well as at C-6 of the galactose 3-O residues; mono-O-substituted galactoses were not detected. 25842315 1 38 theme soluble 99:105 arg1 gum 89:91 a clear gum 81:91 a clear gum 81:91 Acacia tortuosa produces a clear gum, very soluble in water. 25842315 8 39 theme NMR 988:990 arg1 spectra 992:998 The NMR spectra 984:998 The NMR spectra 984:998 The NMR spectra suggest that the carbohydrate links to hydroxyproline through the galactose (galactosylation). 25842315 7 40 theme arabinogalactan-protein 880:902 arg1 complex 904:910 an arabinogalactan-protein complex 877:910 an arabinogalactan-protein complex that binds poorly with β-glucosyl Yariv reagent, and two glycoproteins 877:981 The proteic fraction is probably represented by an arabinogalactan-protein complex that binds poorly with β-glucosyl Yariv reagent, and two glycoproteins. 25842315 4 41 from C-2 548:550 arg1 chains 538:543 lateral chains 530:543 lateral chains at C-2 530:550 The data obtained show that the heteropolysaccharide is an arabinogalactan type II, highly ramified, with lateral chains at C-2 as well as at C-6 of the galactose 3-O residues; mono-O-substituted galactoses were not detected. 25842315 3 42 theme gum 267:269 arg1 structure 271:279 the A. tortuosa gum structure 251:279 the A. tortuosa gum structure 251:279 The elucidation of the A. tortuosa gum structure by the combination of classical chemical methods, size exclusion chromatography and NMR spectroscopy, was the objective of this investigation. 25842315 6 43 theme acid 795:798 arg1 abundance 752:760 The abundance 748:760 The abundance of the 4-O-methyl-α-d-glucuronic acid 748:798 The abundance of the 4-O-methyl-α-d-glucuronic acid was not previously reported. 25842315 5 44 theme pyranose 696:703 arg1 arabinose 685:693 the arabinose 681:693 the arabinose 681:693 There are residues of mannose, the arabinose, pyranose predominantly, is terminal and 2-O-linked. 25842315 5 44 theme pyranose 696:703 arg1 mannose 672:678 mannose 672:678 mannose 672:678 There are residues of mannose, the arabinose, pyranose predominantly, is terminal and 2-O-linked. 25842315 6 45 theme 4-O-methyl-α-d-glucuronic 769:793 arg1 acid 795:798 the 4-O-methyl-α-d-glucuronic acid 765:798 the 4-O-methyl-α-d-glucuronic acid 765:798 The abundance of the 4-O-methyl-α-d-glucuronic acid was not previously reported. 25842315 8 46 attach links 1030:1034 arg1 hydroxyproline 1039:1052 hydroxyproline 1039:1052 hydroxyproline 1039:1052 The NMR spectra suggest that the carbohydrate links to hydroxyproline through the galactose (galactosylation). 25842315 8 46 attach links 1030:1034 arg2 carbohydrate 1017:1028 the carbohydrate 1013:1028 the carbohydrate 1013:1028 The NMR spectra suggest that the carbohydrate links to hydroxyproline through the galactose (galactosylation). 25842315 3 47 theme classical 303:311 arg1 methods 322:328 classical chemical methods 303:328 classical chemical methods 303:328 The elucidation of the A. tortuosa gum structure by the combination of classical chemical methods, size exclusion chromatography and NMR spectroscopy, was the objective of this investigation. 25842315 3 47 theme classical 303:311 arg1 chromatography 346:359 size exclusion chromatography 331:359 size exclusion chromatography 331:359 The elucidation of the A. tortuosa gum structure by the combination of classical chemical methods, size exclusion chromatography and NMR spectroscopy, was the objective of this investigation. 25842315 3 47 theme classical 303:311 arg1 spectroscopy 369:380 NMR spectroscopy 365:380 NMR spectroscopy 365:380 The elucidation of the A. tortuosa gum structure by the combination of classical chemical methods, size exclusion chromatography and NMR spectroscopy, was the objective of this investigation. 25842315 2 48 theme arabinogalactan-protein 199:221 arg1 complex 223:229 an arabinogalactan-protein complex 196:229 one of them an arabinogalactan-protein complex 184:229 Previous reports showed that it was constituted by four fractions, one of them an arabinogalactan-protein complex. 26264169 6 0 theme biosynthetic 1034:1045 arg1 route 1047:1051 an unexpected biosynthetic route 1020:1051 an unexpected biosynthetic route to pacodine 1020:1063 The occurrence of papaverine 7-O-demethylase (P7ODM) expands the enzymatic scope of the 2ODD family in opium poppy and suggests an unexpected biosynthetic route to pacodine. 26264169 1 1 theme several 140:146 arg1 alkaloids 195:203 several pharmacologically important benzylisoquinoline alkaloids 140:203 several pharmacologically important benzylisoquinoline alkaloids including the vasodilator papaverine 140:240 Opium poppy (Papaver somniferum) produces several pharmacologically important benzylisoquinoline alkaloids including the vasodilator papaverine. 26264169 1 1 theme several 140:146 arg1 papaverine 231:240 the vasodilator papaverine 215:240 the vasodilator papaverine 215:240 Opium poppy (Papaver somniferum) produces several pharmacologically important benzylisoquinoline alkaloids including the vasodilator papaverine. 26264169 4 2 theme structural 631:640 arg1 scaffolds 642:650 diverse structural scaffolds 623:650 diverse structural scaffolds 623:650 Three members of the 2-oxoglutarate/Fe(2+)-dependent dioxygenases (2ODDs) family in opium poppy display widespread O-dealkylation activity on several benzylisoquinoline alkaloids with diverse structural scaffolds, and two are responsible for the antepenultimate and ultimate steps in morphine biosynthesis. 26264169 5 3 theme regio-specific 826:839 arg1 7-O-demethylation 841:857 the efficient substrate- and regio-specific 7-O-demethylation 797:857 the efficient substrate- and regio-specific 7-O-demethylation of papaverine yielding pacodine 797:889 We report a novel 2ODD from opium poppy catalyzing the efficient substrate- and regio-specific 7-O-demethylation of papaverine yielding pacodine. 26264169 6 4 theme family 985:990 arg1 scope 967:971 the enzymatic scope 953:971 the enzymatic scope of the 2ODD family 953:990 The occurrence of papaverine 7-O-demethylase (P7ODM) expands the enzymatic scope of the 2ODD family in opium poppy and suggests an unexpected biosynthetic route to pacodine. 26264169 4 5 from poppy 529:533 arg1 members 445:451 Three members 439:451 Three members of the 2-oxoglutarate/Fe(2+)-dependent dioxygenases (2ODDs) family in opium poppy 439:533 Three members of the 2-oxoglutarate/Fe(2+)-dependent dioxygenases (2ODDs) family in opium poppy display widespread O-dealkylation activity on several benzylisoquinoline alkaloids with diverse structural scaffolds, and two are responsible for the antepenultimate and ultimate steps in morphine biosynthesis. 26264169 5 6 from poppy 780:784 arg1 2ODD 764:767 a novel 2ODD 756:767 a novel 2ODD from opium poppy catalyzing the efficient substrate- and regio-specific 7-O-demethylation of papaverine yielding pacodine 756:889 We report a novel 2ODD from opium poppy catalyzing the efficient substrate- and regio-specific 7-O-demethylation of papaverine yielding pacodine. 26264169 4 7 dep -dependent 481:490 arg1 2ODDs 506:510 2ODDs 506:510 2ODDs 506:510 Three members of the 2-oxoglutarate/Fe(2+)-dependent dioxygenases (2ODDs) family in opium poppy display widespread O-dealkylation activity on several benzylisoquinoline alkaloids with diverse structural scaffolds, and two are responsible for the antepenultimate and ultimate steps in morphine biosynthesis. 26264169 4 7 dep -dependent 481:490 arg1 dioxygenases 492:503 dioxygenases 492:503 dioxygenases (2ODDs) 492:511 Three members of the 2-oxoglutarate/Fe(2+)-dependent dioxygenases (2ODDs) family in opium poppy display widespread O-dealkylation activity on several benzylisoquinoline alkaloids with diverse structural scaffolds, and two are responsible for the antepenultimate and ultimate steps in morphine biosynthesis. 26264169 4 8 theme diverse 623:629 arg1 scaffolds 642:650 diverse structural scaffolds 623:650 diverse structural scaffolds 623:650 Three members of the 2-oxoglutarate/Fe(2+)-dependent dioxygenases (2ODDs) family in opium poppy display widespread O-dealkylation activity on several benzylisoquinoline alkaloids with diverse structural scaffolds, and two are responsible for the antepenultimate and ultimate steps in morphine biosynthesis. 26264169 3 9 theme pacodine 390:397 arg1 origin 380:385 the biosynthetic origin 363:385 the biosynthetic origin of pacodine and palaudine 363:411 However, the biosynthetic origin of pacodine and palaudine has not been established. 26264169 6 10 theme 2ODD 980:983 arg1 family 985:990 the 2ODD family 976:990 the 2ODD family 976:990 The occurrence of papaverine 7-O-demethylase (P7ODM) expands the enzymatic scope of the 2ODD family in opium poppy and suggests an unexpected biosynthetic route to pacodine. 26264169 1 11 dep Papaver 111:117 arg1 somniferum 119:128 Papaver somniferum 111:128 Papaver somniferum 111:128 Opium poppy (Papaver somniferum) produces several pharmacologically important benzylisoquinoline alkaloids including the vasodilator papaverine. 26264169 2 12 theme O-linked 330:337 arg1 groups 346:351 four O-linked methyl groups 325:351 four O-linked methyl groups 325:351 Pacodine and palaudine are tri-O-methylated analogs of papaverine, which contains four O-linked methyl groups. 26264169 0 13 theme opium 85:89 arg1 poppy 91:95 opium poppy 85:95 opium poppy 85:95 Papaverine 7-O-demethylase, a novel 2-oxoglutarate/Fe(2+)-dependent dioxygenase from opium poppy. 26264169 4 14 with alkaloids 608:616 arg1 scaffolds 642:650 diverse structural scaffolds 623:650 diverse structural scaffolds 623:650 Three members of the 2-oxoglutarate/Fe(2+)-dependent dioxygenases (2ODDs) family in opium poppy display widespread O-dealkylation activity on several benzylisoquinoline alkaloids with diverse structural scaffolds, and two are responsible for the antepenultimate and ultimate steps in morphine biosynthesis. 26264169 4 15 from family 513:518 arg1 poppy 529:533 opium poppy 523:533 opium poppy 523:533 Three members of the 2-oxoglutarate/Fe(2+)-dependent dioxygenases (2ODDs) family in opium poppy display widespread O-dealkylation activity on several benzylisoquinoline alkaloids with diverse structural scaffolds, and two are responsible for the antepenultimate and ultimate steps in morphine biosynthesis. 26264169 1 16 theme important 166:174 arg1 alkaloids 195:203 several pharmacologically important benzylisoquinoline alkaloids 140:203 several pharmacologically important benzylisoquinoline alkaloids including the vasodilator papaverine 140:240 Opium poppy (Papaver somniferum) produces several pharmacologically important benzylisoquinoline alkaloids including the vasodilator papaverine. 26264169 1 16 theme important 166:174 arg1 papaverine 231:240 the vasodilator papaverine 215:240 the vasodilator papaverine 215:240 Opium poppy (Papaver somniferum) produces several pharmacologically important benzylisoquinoline alkaloids including the vasodilator papaverine. 26264169 4 17 theme family 513:518 arg1 members 445:451 Three members 439:451 Three members of the 2-oxoglutarate/Fe(2+)-dependent dioxygenases (2ODDs) family in opium poppy 439:533 Three members of the 2-oxoglutarate/Fe(2+)-dependent dioxygenases (2ODDs) family in opium poppy display widespread O-dealkylation activity on several benzylisoquinoline alkaloids with diverse structural scaffolds, and two are responsible for the antepenultimate and ultimate steps in morphine biosynthesis. 26264169 4 18 from steps 714:718 arg1 biosynthesis 732:743 morphine biosynthesis 723:743 morphine biosynthesis 723:743 Three members of the 2-oxoglutarate/Fe(2+)-dependent dioxygenases (2ODDs) family in opium poppy display widespread O-dealkylation activity on several benzylisoquinoline alkaloids with diverse structural scaffolds, and two are responsible for the antepenultimate and ultimate steps in morphine biosynthesis. 26264169 1 19 theme benzylisoquinoline 176:193 arg1 alkaloids 195:203 several pharmacologically important benzylisoquinoline alkaloids 140:203 several pharmacologically important benzylisoquinoline alkaloids including the vasodilator papaverine 140:240 Opium poppy (Papaver somniferum) produces several pharmacologically important benzylisoquinoline alkaloids including the vasodilator papaverine. 26264169 1 19 theme benzylisoquinoline 176:193 arg1 papaverine 231:240 the vasodilator papaverine 215:240 the vasodilator papaverine 215:240 Opium poppy (Papaver somniferum) produces several pharmacologically important benzylisoquinoline alkaloids including the vasodilator papaverine. 26264169 5 20 theme pacodine 882:889 arg1 7-O-demethylation 841:857 the efficient substrate- and regio-specific 7-O-demethylation 797:857 the efficient substrate- and regio-specific 7-O-demethylation of papaverine yielding pacodine 797:889 We report a novel 2ODD from opium poppy catalyzing the efficient substrate- and regio-specific 7-O-demethylation of papaverine yielding pacodine. 26264169 6 21 theme enzymatic 957:965 arg1 scope 967:971 the enzymatic scope 953:971 the enzymatic scope of the 2ODD family 953:990 The occurrence of papaverine 7-O-demethylase (P7ODM) expands the enzymatic scope of the 2ODD family in opium poppy and suggests an unexpected biosynthetic route to pacodine. 26264169 5 22 theme efficient 801:809 arg1 7-O-demethylation 841:857 the efficient substrate- and regio-specific 7-O-demethylation 797:857 the efficient substrate- and regio-specific 7-O-demethylation of papaverine yielding pacodine 797:889 We report a novel 2ODD from opium poppy catalyzing the efficient substrate- and regio-specific 7-O-demethylation of papaverine yielding pacodine. 26264169 4 23 theme morphine 723:730 arg1 biosynthesis 732:743 morphine biosynthesis 723:743 morphine biosynthesis 723:743 Three members of the 2-oxoglutarate/Fe(2+)-dependent dioxygenases (2ODDs) family in opium poppy display widespread O-dealkylation activity on several benzylisoquinoline alkaloids with diverse structural scaffolds, and two are responsible for the antepenultimate and ultimate steps in morphine biosynthesis. 26264169 0 24 theme Papaverine 0:9 arg1 dioxygenase 68:78 a novel 2-oxoglutarate/Fe(2+)-dependent dioxygenase 28:78 a novel 2-oxoglutarate/Fe(2+)-dependent dioxygenase from opium poppy 28:95 Papaverine 7-O-demethylase, a novel 2-oxoglutarate/Fe(2+)-dependent dioxygenase from opium poppy. 26264169 0 24 theme Papaverine 0:9 arg1 7-O-demethylase 11:25 Papaverine 7-O-demethylase 0:25 Papaverine 7-O-demethylase 0:25 Papaverine 7-O-demethylase, a novel 2-oxoglutarate/Fe(2+)-dependent dioxygenase from opium poppy. 26264169 4 25 theme benzylisoquinoline 589:606 arg1 alkaloids 608:616 several benzylisoquinoline alkaloids 581:616 several benzylisoquinoline alkaloids with diverse structural scaffolds 581:650 Three members of the 2-oxoglutarate/Fe(2+)-dependent dioxygenases (2ODDs) family in opium poppy display widespread O-dealkylation activity on several benzylisoquinoline alkaloids with diverse structural scaffolds, and two are responsible for the antepenultimate and ultimate steps in morphine biosynthesis. 26264169 5 26 theme opium 774:778 arg1 poppy 780:784 opium poppy 774:784 opium poppy catalyzing the efficient substrate- and regio-specific 7-O-demethylation of papaverine yielding pacodine 774:889 We report a novel 2ODD from opium poppy catalyzing the efficient substrate- and regio-specific 7-O-demethylation of papaverine yielding pacodine. 26264169 3 27 theme palaudine 403:411 arg1 origin 380:385 the biosynthetic origin 363:385 the biosynthetic origin of pacodine and palaudine 363:411 However, the biosynthetic origin of pacodine and palaudine has not been established. 26264169 4 28 theme several 581:587 arg1 alkaloids 608:616 several benzylisoquinoline alkaloids 581:616 several benzylisoquinoline alkaloids with diverse structural scaffolds 581:650 Three members of the 2-oxoglutarate/Fe(2+)-dependent dioxygenases (2ODDs) family in opium poppy display widespread O-dealkylation activity on several benzylisoquinoline alkaloids with diverse structural scaffolds, and two are responsible for the antepenultimate and ultimate steps in morphine biosynthesis. 26264169 2 29 theme methyl 339:344 arg1 groups 346:351 four O-linked methyl groups 325:351 four O-linked methyl groups 325:351 Pacodine and palaudine are tri-O-methylated analogs of papaverine, which contains four O-linked methyl groups. 26264169 6 30 from expands 945:951 arg1 poppy 1001:1005 opium poppy 995:1005 opium poppy 995:1005 The occurrence of papaverine 7-O-demethylase (P7ODM) expands the enzymatic scope of the 2ODD family in opium poppy and suggests an unexpected biosynthetic route to pacodine. 26264169 2 31 contain contains 316:323 arg1 palaudine 256:264 palaudine 256:264 palaudine 256:264 Pacodine and palaudine are tri-O-methylated analogs of papaverine, which contains four O-linked methyl groups. 26264169 2 31 contain contains 316:323 arg1 analogs 287:293 tri-O-methylated analogs 270:293 tri-O-methylated analogs 270:293 Pacodine and palaudine are tri-O-methylated analogs of papaverine, which contains four O-linked methyl groups. 26264169 2 31 contain contains 316:323 arg1 Pacodine 243:250 Pacodine 243:250 Pacodine 243:250 Pacodine and palaudine are tri-O-methylated analogs of papaverine, which contains four O-linked methyl groups. 26264169 2 31 contain contains 316:323 arg2 groups 346:351 four O-linked methyl groups 325:351 four O-linked methyl groups 325:351 Pacodine and palaudine are tri-O-methylated analogs of papaverine, which contains four O-linked methyl groups. 26264169 5 32 theme novel 758:762 arg1 2ODD 764:767 a novel 2ODD 756:767 a novel 2ODD from opium poppy catalyzing the efficient substrate- and regio-specific 7-O-demethylation of papaverine yielding pacodine 756:889 We report a novel 2ODD from opium poppy catalyzing the efficient substrate- and regio-specific 7-O-demethylation of papaverine yielding pacodine. 26264169 1 33 theme Opium 98:102 arg1 Papaver 111:117 Papaver 111:117 Papaver 111:117 Opium poppy (Papaver somniferum) produces several pharmacologically important benzylisoquinoline alkaloids including the vasodilator papaverine. 26264169 1 33 theme Opium 98:102 arg1 poppy 104:108 Opium poppy 98:108 Opium poppy (Papaver somniferum) 98:129 Opium poppy (Papaver somniferum) produces several pharmacologically important benzylisoquinoline alkaloids including the vasodilator papaverine. 26264169 1 34 theme vasodilator 219:229 arg1 papaverine 231:240 the vasodilator papaverine 215:240 the vasodilator papaverine 215:240 Opium poppy (Papaver somniferum) produces several pharmacologically important benzylisoquinoline alkaloids including the vasodilator papaverine. 26264169 6 35 theme unexpected 1023:1032 arg1 route 1047:1051 an unexpected biosynthetic route 1020:1051 an unexpected biosynthetic route to pacodine 1020:1063 The occurrence of papaverine 7-O-demethylase (P7ODM) expands the enzymatic scope of the 2ODD family in opium poppy and suggests an unexpected biosynthetic route to pacodine. 26264169 0 36 theme novel 30:34 arg1 dioxygenase 68:78 a novel 2-oxoglutarate/Fe(2+)-dependent dioxygenase 28:78 a novel 2-oxoglutarate/Fe(2+)-dependent dioxygenase from opium poppy 28:95 Papaverine 7-O-demethylase, a novel 2-oxoglutarate/Fe(2+)-dependent dioxygenase from opium poppy. 26264169 0 36 theme novel 30:34 arg1 7-O-demethylase 11:25 Papaverine 7-O-demethylase 0:25 Papaverine 7-O-demethylase 0:25 Papaverine 7-O-demethylase, a novel 2-oxoglutarate/Fe(2+)-dependent dioxygenase from opium poppy. 26264169 4 37 theme O-dealkylation 554:567 arg1 activity 569:576 widespread O-dealkylation activity 543:576 widespread O-dealkylation activity on several benzylisoquinoline alkaloids with diverse structural scaffolds 543:650 Three members of the 2-oxoglutarate/Fe(2+)-dependent dioxygenases (2ODDs) family in opium poppy display widespread O-dealkylation activity on several benzylisoquinoline alkaloids with diverse structural scaffolds, and two are responsible for the antepenultimate and ultimate steps in morphine biosynthesis. 26264169 4 38 from activity 569:576 arg1 alkaloids 608:616 several benzylisoquinoline alkaloids 581:616 several benzylisoquinoline alkaloids with diverse structural scaffolds 581:650 Three members of the 2-oxoglutarate/Fe(2+)-dependent dioxygenases (2ODDs) family in opium poppy display widespread O-dealkylation activity on several benzylisoquinoline alkaloids with diverse structural scaffolds, and two are responsible for the antepenultimate and ultimate steps in morphine biosynthesis. 26264169 4 39 theme antepenultimate 685:699 arg1 steps 714:718 the antepenultimate and ultimate steps 681:718 the antepenultimate and ultimate steps in morphine biosynthesis 681:743 Three members of the 2-oxoglutarate/Fe(2+)-dependent dioxygenases (2ODDs) family in opium poppy display widespread O-dealkylation activity on several benzylisoquinoline alkaloids with diverse structural scaffolds, and two are responsible for the antepenultimate and ultimate steps in morphine biosynthesis. 26264169 5 40 theme papaverine 862:871 arg1 pacodine 882:889 papaverine yielding pacodine 862:889 papaverine yielding pacodine 862:889 We report a novel 2ODD from opium poppy catalyzing the efficient substrate- and regio-specific 7-O-demethylation of papaverine yielding pacodine. 26264169 2 41 link O-linked 330:337 arg1 groups 346:351 four O-linked methyl groups 325:351 four O-linked methyl groups 325:351 Pacodine and palaudine are tri-O-methylated analogs of papaverine, which contains four O-linked methyl groups. 26264169 4 42 theme -dependent 481:490 arg1 family 513:518 the 2-oxoglutarate/Fe(2+)-dependent dioxygenases (2ODDs) family 456:518 the 2-oxoglutarate/Fe(2+)-dependent dioxygenases (2ODDs) family in opium poppy 456:533 Three members of the 2-oxoglutarate/Fe(2+)-dependent dioxygenases (2ODDs) family in opium poppy display widespread O-dealkylation activity on several benzylisoquinoline alkaloids with diverse structural scaffolds, and two are responsible for the antepenultimate and ultimate steps in morphine biosynthesis. 26264169 5 43 theme yielding 873:880 arg1 pacodine 882:889 papaverine yielding pacodine 862:889 papaverine yielding pacodine 862:889 We report a novel 2ODD from opium poppy catalyzing the efficient substrate- and regio-specific 7-O-demethylation of papaverine yielding pacodine. 26264169 6 44 theme opium 995:999 arg1 poppy 1001:1005 opium poppy 995:1005 opium poppy 995:1005 The occurrence of papaverine 7-O-demethylase (P7ODM) expands the enzymatic scope of the 2ODD family in opium poppy and suggests an unexpected biosynthetic route to pacodine. 26264169 6 45 theme 7-O-demethylase 921:935 arg1 occurrence 896:905 The occurrence 892:905 The occurrence of papaverine 7-O-demethylase (P7ODM) 892:943 The occurrence of papaverine 7-O-demethylase (P7ODM) expands the enzymatic scope of the 2ODD family in opium poppy and suggests an unexpected biosynthetic route to pacodine. 26264169 2 46 theme papaverine 298:307 arg1 palaudine 256:264 palaudine 256:264 palaudine 256:264 Pacodine and palaudine are tri-O-methylated analogs of papaverine, which contains four O-linked methyl groups. 26264169 2 46 theme papaverine 298:307 arg1 analogs 287:293 tri-O-methylated analogs 270:293 tri-O-methylated analogs 270:293 Pacodine and palaudine are tri-O-methylated analogs of papaverine, which contains four O-linked methyl groups. 26264169 2 46 theme papaverine 298:307 arg1 Pacodine 243:250 Pacodine 243:250 Pacodine 243:250 Pacodine and palaudine are tri-O-methylated analogs of papaverine, which contains four O-linked methyl groups. 26264169 5 47 theme substrate- 811:820 arg1 7-O-demethylation 841:857 the efficient substrate- and regio-specific 7-O-demethylation 797:857 the efficient substrate- and regio-specific 7-O-demethylation of papaverine yielding pacodine 797:889 We report a novel 2ODD from opium poppy catalyzing the efficient substrate- and regio-specific 7-O-demethylation of papaverine yielding pacodine. 26264169 0 48 from poppy 91:95 arg1 dioxygenase 68:78 a novel 2-oxoglutarate/Fe(2+)-dependent dioxygenase 28:78 a novel 2-oxoglutarate/Fe(2+)-dependent dioxygenase from opium poppy 28:95 Papaverine 7-O-demethylase, a novel 2-oxoglutarate/Fe(2+)-dependent dioxygenase from opium poppy. 26264169 0 48 from poppy 91:95 arg1 7-O-demethylase 11:25 Papaverine 7-O-demethylase 0:25 Papaverine 7-O-demethylase 0:25 Papaverine 7-O-demethylase, a novel 2-oxoglutarate/Fe(2+)-dependent dioxygenase from opium poppy. 26264169 4 49 from members 445:451 arg1 poppy 529:533 opium poppy 523:533 opium poppy 523:533 Three members of the 2-oxoglutarate/Fe(2+)-dependent dioxygenases (2ODDs) family in opium poppy display widespread O-dealkylation activity on several benzylisoquinoline alkaloids with diverse structural scaffolds, and two are responsible for the antepenultimate and ultimate steps in morphine biosynthesis. 26264169 0 50 theme -dependent 57:66 arg1 dioxygenase 68:78 a novel 2-oxoglutarate/Fe(2+)-dependent dioxygenase 28:78 a novel 2-oxoglutarate/Fe(2+)-dependent dioxygenase from opium poppy 28:95 Papaverine 7-O-demethylase, a novel 2-oxoglutarate/Fe(2+)-dependent dioxygenase from opium poppy. 26264169 0 50 theme -dependent 57:66 arg1 7-O-demethylase 11:25 Papaverine 7-O-demethylase 0:25 Papaverine 7-O-demethylase 0:25 Papaverine 7-O-demethylase, a novel 2-oxoglutarate/Fe(2+)-dependent dioxygenase from opium poppy. 26264169 6 51 theme papaverine 910:919 arg1 7-O-demethylase 921:935 papaverine 7-O-demethylase 910:935 papaverine 7-O-demethylase (P7ODM) 910:943 The occurrence of papaverine 7-O-demethylase (P7ODM) expands the enzymatic scope of the 2ODD family in opium poppy and suggests an unexpected biosynthetic route to pacodine. 26264169 6 51 theme papaverine 910:919 arg1 P7ODM 938:942 P7ODM 938:942 P7ODM 938:942 The occurrence of papaverine 7-O-demethylase (P7ODM) expands the enzymatic scope of the 2ODD family in opium poppy and suggests an unexpected biosynthetic route to pacodine. 26264169 4 52 theme ultimate 705:712 arg1 steps 714:718 the antepenultimate and ultimate steps 681:718 the antepenultimate and ultimate steps in morphine biosynthesis 681:743 Three members of the 2-oxoglutarate/Fe(2+)-dependent dioxygenases (2ODDs) family in opium poppy display widespread O-dealkylation activity on several benzylisoquinoline alkaloids with diverse structural scaffolds, and two are responsible for the antepenultimate and ultimate steps in morphine biosynthesis. 26264169 3 53 theme biosynthetic 367:378 arg1 origin 380:385 the biosynthetic origin 363:385 the biosynthetic origin of pacodine and palaudine 363:411 However, the biosynthetic origin of pacodine and palaudine has not been established. 26264169 4 54 theme opium 523:527 arg1 poppy 529:533 opium poppy 523:533 opium poppy 523:533 Three members of the 2-oxoglutarate/Fe(2+)-dependent dioxygenases (2ODDs) family in opium poppy display widespread O-dealkylation activity on several benzylisoquinoline alkaloids with diverse structural scaffolds, and two are responsible for the antepenultimate and ultimate steps in morphine biosynthesis. 26264169 2 55 theme tri-O-methylated 270:285 arg1 palaudine 256:264 palaudine 256:264 palaudine 256:264 Pacodine and palaudine are tri-O-methylated analogs of papaverine, which contains four O-linked methyl groups. 26264169 2 55 theme tri-O-methylated 270:285 arg1 analogs 287:293 tri-O-methylated analogs 270:293 tri-O-methylated analogs 270:293 Pacodine and palaudine are tri-O-methylated analogs of papaverine, which contains four O-linked methyl groups. 26264169 2 55 theme tri-O-methylated 270:285 arg1 Pacodine 243:250 Pacodine 243:250 Pacodine 243:250 Pacodine and palaudine are tri-O-methylated analogs of papaverine, which contains four O-linked methyl groups. 26264169 4 56 theme widespread 543:552 arg1 activity 569:576 widespread O-dealkylation activity 543:576 widespread O-dealkylation activity on several benzylisoquinoline alkaloids with diverse structural scaffolds 543:650 Three members of the 2-oxoglutarate/Fe(2+)-dependent dioxygenases (2ODDs) family in opium poppy display widespread O-dealkylation activity on several benzylisoquinoline alkaloids with diverse structural scaffolds, and two are responsible for the antepenultimate and ultimate steps in morphine biosynthesis. 26125729 2 0 theme b1,3-galactosyltransferase 492:517 arg1 core 482:485 the core 478:485 the core of 1 b1,3-galactosyltransferase (C1GalT1) 478:527 Analyses of serum IgA1 from IgAN patients revealed abnormal galactosylation of the O-linked carbohydrate moieties of IgA that may result from altered activity in the core of 1 b1,3-galactosyltransferase (C1GalT1). 26125729 4 1 theme healthy 742:748 arg1 controls 750:757 180 healthy controls 738:757 180 healthy controls 738:757 A total of 180 IgAN patients and 180 healthy controls were recruited for the study. 26125729 2 2 theme abnormal 367:374 arg1 galactosylation 376:390 abnormal galactosylation 367:390 abnormal galactosylation of the O-linked carbohydrate moieties of IgA that may result from altered activity in the core of 1 b1,3-galactosyltransferase (C1GalT1) 367:527 Analyses of serum IgA1 from IgAN patients revealed abnormal galactosylation of the O-linked carbohydrate moieties of IgA that may result from altered activity in the core of 1 b1,3-galactosyltransferase (C1GalT1). 26125729 3 3 from population 684:693 arg1 cohorts 660:666 cohorts 660:666 cohorts from the Uyghur population in China 660:702 To evaluate the association between C1GalT1 single nucleotide polymorphisms (SNPs) and IgAN, we performed a case-control study on cohorts from the Uyghur population in China. 26125729 3 3 from population 684:693 arg1 China 698:702 China 698:702 China 698:702 To evaluate the association between C1GalT1 single nucleotide polymorphisms (SNPs) and IgAN, we performed a case-control study on cohorts from the Uyghur population in China. 26125729 2 4 from activity 466:473 arg1 core 482:485 the core 478:485 the core of 1 b1,3-galactosyltransferase (C1GalT1) 478:527 Analyses of serum IgA1 from IgAN patients revealed abnormal galactosylation of the O-linked carbohydrate moieties of IgA that may result from altered activity in the core of 1 b1,3-galactosyltransferase (C1GalT1). 26125729 6 5 theme allele 986:991 arg1 higher 1058:1063 higher 1058:1063 higher 1058:1063 The frequencies of the I allele and DI genotype of rs5882115 in IgAN patients were significantly higher than those in controls (P < 0.05). 26125729 6 5 theme allele 986:991 arg1 frequencies 965:975 The frequencies 961:975 The frequencies of the I allele and DI genotype of rs5882115 in IgAN patients 961:1037 The frequencies of the I allele and DI genotype of rs5882115 in IgAN patients were significantly higher than those in controls (P < 0.05). 26125729 8 6 from Polymorphisms 1216:1228 arg1 gene 1245:1248 the C1GALT1 gene 1233:1248 the C1GALT1 gene 1233:1248 Polymorphisms in the C1GALT1 gene were associated with genetic susceptibility to Uyghur IgAN. 26125729 5 7 theme eligible 938:945 arg1 participants 947:958 all eligible participants 934:958 all eligible participants 934:958 We sequenced 5 SNPs, including SNP1 (rs9639031), SNP2 (-527A/G), SNP3 (rs1008898), SNP4 (rs5882115), and SNP5 (rs1047763) in the C1GalT1 gene in all eligible participants. 26125729 6 8 from frequencies 965:975 arg1 patients 1030:1037 IgAN patients 1025:1037 IgAN patients 1025:1037 The frequencies of the I allele and DI genotype of rs5882115 in IgAN patients were significantly higher than those in controls (P < 0.05). 26125729 1 9 theme mesangial 255:263 arg1 proliferation 265:277 mesangial proliferation 255:277 mesangial proliferation 255:277 Immunoglobulin A (IgA) nephropathy (IgAN) is a common form of primary glomerulonephritis characterized by diffuse glomerular mesangial IgA1 deposition leading to mesangial proliferation and chronic glomerular inflammation. 26125729 3 10 from study 651:655 arg1 cohorts 660:666 cohorts 660:666 cohorts from the Uyghur population in China 660:702 To evaluate the association between C1GalT1 single nucleotide polymorphisms (SNPs) and IgAN, we performed a case-control study on cohorts from the Uyghur population in China. 26125729 4 11 theme controls 750:757 arg1 total 707:711 A total 705:711 A total of 180 IgAN patients and 180 healthy controls 705:757 A total of 180 IgAN patients and 180 healthy controls were recruited for the study. 26125729 2 12 from patients 349:356 arg1 Analyses 316:323 Analyses 316:323 Analyses of serum IgA1 from IgAN patients 316:356 Analyses of serum IgA1 from IgAN patients revealed abnormal galactosylation of the O-linked carbohydrate moieties of IgA that may result from altered activity in the core of 1 b1,3-galactosyltransferase (C1GalT1). 26125729 2 12 from patients 349:356 arg1 IgA1 334:337 serum IgA1 328:337 serum IgA1 from IgAN patients 328:356 Analyses of serum IgA1 from IgAN patients revealed abnormal galactosylation of the O-linked carbohydrate moieties of IgA that may result from altered activity in the core of 1 b1,3-galactosyltransferase (C1GalT1). 26125729 3 13 theme C1GalT1 566:572 arg1 SNPs 607:610 SNPs 607:610 SNPs 607:610 To evaluate the association between C1GalT1 single nucleotide polymorphisms (SNPs) and IgAN, we performed a case-control study on cohorts from the Uyghur population in China. 26125729 3 13 theme C1GalT1 566:572 arg1 polymorphisms 592:604 C1GalT1 single nucleotide polymorphisms 566:604 C1GalT1 single nucleotide polymorphisms (SNPs) 566:611 To evaluate the association between C1GalT1 single nucleotide polymorphisms (SNPs) and IgAN, we performed a case-control study on cohorts from the Uyghur population in China. 26125729 4 14 theme patients 725:732 arg1 total 707:711 A total 705:711 A total of 180 IgAN patients and 180 healthy controls 705:757 A total of 180 IgAN patients and 180 healthy controls were recruited for the study. 26125729 6 15 theme I 984:984 arg1 allele 986:991 I allele 984:991 I allele 984:991 The frequencies of the I allele and DI genotype of rs5882115 in IgAN patients were significantly higher than those in controls (P < 0.05). 26125729 1 16 theme common 140:145 arg1 nephropathy 116:126 Immunoglobulin A (IgA) nephropathy 93:126 Immunoglobulin A (IgA) nephropathy (IgAN) 93:133 Immunoglobulin A (IgA) nephropathy (IgAN) is a common form of primary glomerulonephritis characterized by diffuse glomerular mesangial IgA1 deposition leading to mesangial proliferation and chronic glomerular inflammation. 26125729 1 16 theme common 140:145 arg1 form 147:150 a common form 138:150 a common form of primary glomerulonephritis characterized by diffuse glomerular mesangial IgA1 deposition leading to mesangial proliferation and chronic glomerular inflammation 138:313 Immunoglobulin A (IgA) nephropathy (IgAN) is a common form of primary glomerulonephritis characterized by diffuse glomerular mesangial IgA1 deposition leading to mesangial proliferation and chronic glomerular inflammation. 26125729 6 17 theme rs5882115 1012:1020 arg1 allele 986:991 I allele 984:991 I allele 984:991 The frequencies of the I allele and DI genotype of rs5882115 in IgAN patients were significantly higher than those in controls (P < 0.05). 26125729 6 17 theme rs5882115 1012:1020 arg1 genotype 1000:1007 DI genotype 997:1007 DI genotype 997:1007 The frequencies of the I allele and DI genotype of rs5882115 in IgAN patients were significantly higher than those in controls (P < 0.05). 26125729 7 18 dep higher 1151:1156 arg1 = 1206:1206 = 1206:1206 = 1206:1206 The frequency of haplotype GAGDA was significantly higher in patients than in controls (0.0719 vs 0.00, P = 0.024). 26125729 2 19 theme carbohydrate 408:419 arg1 moieties 421:428 the O-linked carbohydrate moieties 395:428 the O-linked carbohydrate moieties of IgA 395:435 Analyses of serum IgA1 from IgAN patients revealed abnormal galactosylation of the O-linked carbohydrate moieties of IgA that may result from altered activity in the core of 1 b1,3-galactosyltransferase (C1GalT1). 26125729 2 20 theme serum 328:332 arg1 IgA1 334:337 serum IgA1 328:337 serum IgA1 from IgAN patients 328:356 Analyses of serum IgA1 from IgAN patients revealed abnormal galactosylation of the O-linked carbohydrate moieties of IgA that may result from altered activity in the core of 1 b1,3-galactosyltransferase (C1GalT1). 26125729 2 21 theme O-linked 399:406 arg1 moieties 421:428 the O-linked carbohydrate moieties 395:428 the O-linked carbohydrate moieties of IgA 395:435 Analyses of serum IgA1 from IgAN patients revealed abnormal galactosylation of the O-linked carbohydrate moieties of IgA that may result from altered activity in the core of 1 b1,3-galactosyltransferase (C1GalT1). 26125729 2 22 theme altered 458:464 arg1 activity 466:473 altered activity 458:473 altered activity in the core of 1 b1,3-galactosyltransferase (C1GalT1) 458:527 Analyses of serum IgA1 from IgAN patients revealed abnormal galactosylation of the O-linked carbohydrate moieties of IgA that may result from altered activity in the core of 1 b1,3-galactosyltransferase (C1GalT1). 26125729 1 23 theme Immunoglobulin 93:106 arg1 IgA 111:113 IgA 111:113 IgA 111:113 Immunoglobulin A (IgA) nephropathy (IgAN) is a common form of primary glomerulonephritis characterized by diffuse glomerular mesangial IgA1 deposition leading to mesangial proliferation and chronic glomerular inflammation. 26125729 1 23 theme Immunoglobulin 93:106 arg1 A 108:108 Immunoglobulin A 93:108 Immunoglobulin A (IgA) nephropathy (IgAN) 93:133 Immunoglobulin A (IgA) nephropathy (IgAN) is a common form of primary glomerulonephritis characterized by diffuse glomerular mesangial IgA1 deposition leading to mesangial proliferation and chronic glomerular inflammation. 26125729 1 24 theme primary 155:161 arg1 glomerulonephritis 163:180 primary glomerulonephritis 155:180 primary glomerulonephritis 155:180 Immunoglobulin A (IgA) nephropathy (IgAN) is a common form of primary glomerulonephritis characterized by diffuse glomerular mesangial IgA1 deposition leading to mesangial proliferation and chronic glomerular inflammation. 26125729 1 25 theme chronic 283:289 arg1 inflammation 302:313 chronic glomerular inflammation 283:313 chronic glomerular inflammation 283:313 Immunoglobulin A (IgA) nephropathy (IgAN) is a common form of primary glomerulonephritis characterized by diffuse glomerular mesangial IgA1 deposition leading to mesangial proliferation and chronic glomerular inflammation. 26125729 1 26 theme A 108:108 arg1 nephropathy 116:126 Immunoglobulin A (IgA) nephropathy 93:126 Immunoglobulin A (IgA) nephropathy (IgAN) 93:133 Immunoglobulin A (IgA) nephropathy (IgAN) is a common form of primary glomerulonephritis characterized by diffuse glomerular mesangial IgA1 deposition leading to mesangial proliferation and chronic glomerular inflammation. 26125729 1 26 theme A 108:108 arg1 form 147:150 a common form 138:150 a common form of primary glomerulonephritis characterized by diffuse glomerular mesangial IgA1 deposition leading to mesangial proliferation and chronic glomerular inflammation 138:313 Immunoglobulin A (IgA) nephropathy (IgAN) is a common form of primary glomerulonephritis characterized by diffuse glomerular mesangial IgA1 deposition leading to mesangial proliferation and chronic glomerular inflammation. 26125729 1 26 theme A 108:108 arg1 IgAN 129:132 IgAN 129:132 IgAN 129:132 Immunoglobulin A (IgA) nephropathy (IgAN) is a common form of primary glomerulonephritis characterized by diffuse glomerular mesangial IgA1 deposition leading to mesangial proliferation and chronic glomerular inflammation. 26125729 6 27 from patients 1030:1037 arg1 higher 1058:1063 higher 1058:1063 higher 1058:1063 The frequencies of the I allele and DI genotype of rs5882115 in IgAN patients were significantly higher than those in controls (P < 0.05). 26125729 6 27 from patients 1030:1037 arg1 frequencies 965:975 The frequencies 961:975 The frequencies of the I allele and DI genotype of rs5882115 in IgAN patients 961:1037 The frequencies of the I allele and DI genotype of rs5882115 in IgAN patients were significantly higher than those in controls (P < 0.05). 26125729 1 28 theme glomerulonephritis 163:180 arg1 nephropathy 116:126 Immunoglobulin A (IgA) nephropathy 93:126 Immunoglobulin A (IgA) nephropathy (IgAN) 93:133 Immunoglobulin A (IgA) nephropathy (IgAN) is a common form of primary glomerulonephritis characterized by diffuse glomerular mesangial IgA1 deposition leading to mesangial proliferation and chronic glomerular inflammation. 26125729 1 28 theme glomerulonephritis 163:180 arg1 form 147:150 a common form 138:150 a common form of primary glomerulonephritis characterized by diffuse glomerular mesangial IgA1 deposition leading to mesangial proliferation and chronic glomerular inflammation 138:313 Immunoglobulin A (IgA) nephropathy (IgAN) is a common form of primary glomerulonephritis characterized by diffuse glomerular mesangial IgA1 deposition leading to mesangial proliferation and chronic glomerular inflammation. 26125729 0 29 theme C1GALT1 20:26 arg1 variants 28:35 C1GALT1 variants 20:35 C1GALT1 variants 20:35 Association between C1GALT1 variants and genetic susceptibility to IgA nephropathy in Uygur. 26125729 1 30 theme glomerular 291:300 arg1 inflammation 302:313 chronic glomerular inflammation 283:313 chronic glomerular inflammation 283:313 Immunoglobulin A (IgA) nephropathy (IgAN) is a common form of primary glomerulonephritis characterized by diffuse glomerular mesangial IgA1 deposition leading to mesangial proliferation and chronic glomerular inflammation. 26125729 2 31 link O-linked 399:406 arg1 moieties 421:428 the O-linked carbohydrate moieties 395:428 the O-linked carbohydrate moieties of IgA 395:435 Analyses of serum IgA1 from IgAN patients revealed abnormal galactosylation of the O-linked carbohydrate moieties of IgA that may result from altered activity in the core of 1 b1,3-galactosyltransferase (C1GalT1). 26125729 3 32 theme nucleotide 581:590 arg1 SNPs 607:610 SNPs 607:610 SNPs 607:610 To evaluate the association between C1GalT1 single nucleotide polymorphisms (SNPs) and IgAN, we performed a case-control study on cohorts from the Uyghur population in China. 26125729 3 32 theme nucleotide 581:590 arg1 polymorphisms 592:604 C1GalT1 single nucleotide polymorphisms 566:604 C1GalT1 single nucleotide polymorphisms (SNPs) 566:611 To evaluate the association between C1GalT1 single nucleotide polymorphisms (SNPs) and IgAN, we performed a case-control study on cohorts from the Uyghur population in China. 26125729 3 33 theme case-control 638:649 arg1 study 651:655 a case-control study 636:655 a case-control study on cohorts from the Uyghur population in China 636:702 To evaluate the association between C1GalT1 single nucleotide polymorphisms (SNPs) and IgAN, we performed a case-control study on cohorts from the Uyghur population in China. 26125729 7 34 theme GAGDA 1127:1131 arg1 higher 1151:1156 higher 1151:1156 higher 1151:1156 The frequency of haplotype GAGDA was significantly higher in patients than in controls (0.0719 vs 0.00, P = 0.024). 26125729 7 34 theme GAGDA 1127:1131 arg1 frequency 1104:1112 The frequency 1100:1112 The frequency of haplotype GAGDA 1100:1131 The frequency of haplotype GAGDA was significantly higher in patients than in controls (0.0719 vs 0.00, P = 0.024). 26125729 0 35 theme genetic 41:47 arg1 susceptibility 49:62 genetic susceptibility 41:62 genetic susceptibility 41:62 Association between C1GALT1 variants and genetic susceptibility to IgA nephropathy in Uygur. 26125729 5 36 theme C1GalT1 918:924 arg1 gene 926:929 the C1GalT1 gene 914:929 the C1GalT1 gene in all eligible participants 914:958 We sequenced 5 SNPs, including SNP1 (rs9639031), SNP2 (-527A/G), SNP3 (rs1008898), SNP4 (rs5882115), and SNP5 (rs1047763) in the C1GalT1 gene in all eligible participants. 26125729 5 37 from gene 926:929 arg1 participants 947:958 all eligible participants 934:958 all eligible participants 934:958 We sequenced 5 SNPs, including SNP1 (rs9639031), SNP2 (-527A/G), SNP3 (rs1008898), SNP4 (rs5882115), and SNP5 (rs1047763) in the C1GalT1 gene in all eligible participants. 26125729 2 38 theme IgA 433:435 arg1 moieties 421:428 the O-linked carbohydrate moieties 395:428 the O-linked carbohydrate moieties of IgA 395:435 Analyses of serum IgA1 from IgAN patients revealed abnormal galactosylation of the O-linked carbohydrate moieties of IgA that may result from altered activity in the core of 1 b1,3-galactosyltransferase (C1GalT1). 26125729 2 39 theme moieties 421:428 arg1 galactosylation 376:390 abnormal galactosylation 367:390 abnormal galactosylation of the O-linked carbohydrate moieties of IgA that may result from altered activity in the core of 1 b1,3-galactosyltransferase (C1GalT1) 367:527 Analyses of serum IgA1 from IgAN patients revealed abnormal galactosylation of the O-linked carbohydrate moieties of IgA that may result from altered activity in the core of 1 b1,3-galactosyltransferase (C1GalT1). 26125729 0 40 from nephropathy 71:81 arg1 Uygur 86:90 Uygur 86:90 Uygur 86:90 Association between C1GALT1 variants and genetic susceptibility to IgA nephropathy in Uygur. 26125729 6 41 dep allele 986:991 arg1 the 980:982 the 980:982 the 980:982 The frequencies of the I allele and DI genotype of rs5882115 in IgAN patients were significantly higher than those in controls (P < 0.05). 26125729 1 42 theme diffuse 199:205 arg1 deposition 233:242 diffuse glomerular mesangial IgA1 deposition 199:242 diffuse glomerular mesangial IgA1 deposition leading to mesangial proliferation and chronic glomerular inflammation 199:313 Immunoglobulin A (IgA) nephropathy (IgAN) is a common form of primary glomerulonephritis characterized by diffuse glomerular mesangial IgA1 deposition leading to mesangial proliferation and chronic glomerular inflammation. 26125729 7 43 theme haplotype 1117:1125 arg1 GAGDA 1127:1131 haplotype GAGDA 1117:1131 haplotype GAGDA 1117:1131 The frequency of haplotype GAGDA was significantly higher in patients than in controls (0.0719 vs 0.00, P = 0.024). 26125729 6 44 theme IgAN 1025:1028 arg1 patients 1030:1037 IgAN patients 1025:1037 IgAN patients 1025:1037 The frequencies of the I allele and DI genotype of rs5882115 in IgAN patients were significantly higher than those in controls (P < 0.05). 26125729 3 45 theme Uyghur 677:682 arg1 population 684:693 the Uyghur population 673:693 the Uyghur population in China 673:702 To evaluate the association between C1GalT1 single nucleotide polymorphisms (SNPs) and IgAN, we performed a case-control study on cohorts from the Uyghur population in China. 26125729 2 46 theme IgAN 344:347 arg1 patients 349:356 IgAN patients 344:356 IgAN patients 344:356 Analyses of serum IgA1 from IgAN patients revealed abnormal galactosylation of the O-linked carbohydrate moieties of IgA that may result from altered activity in the core of 1 b1,3-galactosyltransferase (C1GalT1). 26125729 8 47 theme genetic 1271:1277 arg1 susceptibility 1279:1292 genetic susceptibility 1271:1292 genetic susceptibility to Uyghur IgAN 1271:1307 Polymorphisms in the C1GALT1 gene were associated with genetic susceptibility to Uyghur IgAN. 26125729 8 48 theme C1GALT1 1237:1243 arg1 gene 1245:1248 the C1GALT1 gene 1233:1248 the C1GALT1 gene 1233:1248 Polymorphisms in the C1GALT1 gene were associated with genetic susceptibility to Uyghur IgAN. 26125729 4 49 theme IgAN 720:723 arg1 patients 725:732 180 IgAN patients 716:732 180 IgAN patients 716:732 A total of 180 IgAN patients and 180 healthy controls were recruited for the study. 26125729 3 50 theme single 574:579 arg1 SNPs 607:610 SNPs 607:610 SNPs 607:610 To evaluate the association between C1GalT1 single nucleotide polymorphisms (SNPs) and IgAN, we performed a case-control study on cohorts from the Uyghur population in China. 26125729 3 50 theme single 574:579 arg1 polymorphisms 592:604 C1GalT1 single nucleotide polymorphisms 566:604 C1GalT1 single nucleotide polymorphisms (SNPs) 566:611 To evaluate the association between C1GalT1 single nucleotide polymorphisms (SNPs) and IgAN, we performed a case-control study on cohorts from the Uyghur population in China. 26125729 1 51 theme glomerular 207:216 arg1 deposition 233:242 diffuse glomerular mesangial IgA1 deposition 199:242 diffuse glomerular mesangial IgA1 deposition leading to mesangial proliferation and chronic glomerular inflammation 199:313 Immunoglobulin A (IgA) nephropathy (IgAN) is a common form of primary glomerulonephritis characterized by diffuse glomerular mesangial IgA1 deposition leading to mesangial proliferation and chronic glomerular inflammation. 26125729 7 52 dep = 1206:1206 arg1 0.00 1198:1201 0.00 1198:1201 0.00 1198:1201 The frequency of haplotype GAGDA was significantly higher in patients than in controls (0.0719 vs 0.00, P = 0.024). 26125729 7 52 dep = 1206:1206 arg1 0.0719 1188:1193 0.0719 1188:1193 0.0719 1188:1193 The frequency of haplotype GAGDA was significantly higher in patients than in controls (0.0719 vs 0.00, P = 0.024). 26125729 2 53 theme IgA1 334:337 arg1 Analyses 316:323 Analyses 316:323 Analyses of serum IgA1 from IgAN patients 316:356 Analyses of serum IgA1 from IgAN patients revealed abnormal galactosylation of the O-linked carbohydrate moieties of IgA that may result from altered activity in the core of 1 b1,3-galactosyltransferase (C1GalT1). 26125729 1 54 theme mesangial 218:226 arg1 deposition 233:242 diffuse glomerular mesangial IgA1 deposition 199:242 diffuse glomerular mesangial IgA1 deposition leading to mesangial proliferation and chronic glomerular inflammation 199:313 Immunoglobulin A (IgA) nephropathy (IgAN) is a common form of primary glomerulonephritis characterized by diffuse glomerular mesangial IgA1 deposition leading to mesangial proliferation and chronic glomerular inflammation. 26125729 6 55 theme P 1089:1089 arg1 < 1091:1091 P < 0.05 1089:1096 P < 0.05 1089:1096 The frequencies of the I allele and DI genotype of rs5882115 in IgAN patients were significantly higher than those in controls (P < 0.05). 26125729 6 55 theme P 1089:1089 arg1 controls 1079:1086 controls 1079:1086 controls (P < 0.05) 1079:1097 The frequencies of the I allele and DI genotype of rs5882115 in IgAN patients were significantly higher than those in controls (P < 0.05). 26125729 6 56 from allele 986:991 arg1 patients 1030:1037 IgAN patients 1025:1037 IgAN patients 1025:1037 The frequencies of the I allele and DI genotype of rs5882115 in IgAN patients were significantly higher than those in controls (P < 0.05). 26125729 6 57 theme genotype 1000:1007 arg1 higher 1058:1063 higher 1058:1063 higher 1058:1063 The frequencies of the I allele and DI genotype of rs5882115 in IgAN patients were significantly higher than those in controls (P < 0.05). 26125729 6 57 theme genotype 1000:1007 arg1 frequencies 965:975 The frequencies 961:975 The frequencies of the I allele and DI genotype of rs5882115 in IgAN patients 961:1037 The frequencies of the I allele and DI genotype of rs5882115 in IgAN patients were significantly higher than those in controls (P < 0.05). 26125729 1 58 theme IgA1 228:231 arg1 deposition 233:242 diffuse glomerular mesangial IgA1 deposition 199:242 diffuse glomerular mesangial IgA1 deposition leading to mesangial proliferation and chronic glomerular inflammation 199:313 Immunoglobulin A (IgA) nephropathy (IgAN) is a common form of primary glomerulonephritis characterized by diffuse glomerular mesangial IgA1 deposition leading to mesangial proliferation and chronic glomerular inflammation. 26125729 0 59 theme IgA 67:69 arg1 nephropathy 71:81 IgA nephropathy 67:81 IgA nephropathy in Uygur 67:90 Association between C1GALT1 variants and genetic susceptibility to IgA nephropathy in Uygur. 26125729 6 60 from genotype 1000:1007 arg1 patients 1030:1037 IgAN patients 1025:1037 IgAN patients 1025:1037 The frequencies of the I allele and DI genotype of rs5882115 in IgAN patients were significantly higher than those in controls (P < 0.05). 26125729 6 61 theme DI 997:998 arg1 genotype 1000:1007 DI genotype 997:1007 DI genotype 997:1007 The frequencies of the I allele and DI genotype of rs5882115 in IgAN patients were significantly higher than those in controls (P < 0.05). 26125729 2 62 from Analyses 316:323 arg1 patients 349:356 IgAN patients 344:356 IgAN patients 344:356 Analyses of serum IgA1 from IgAN patients revealed abnormal galactosylation of the O-linked carbohydrate moieties of IgA that may result from altered activity in the core of 1 b1,3-galactosyltransferase (C1GalT1). 27845045 7 0 theme mice 1175:1178 arg1 lungs 1154:1158 the lungs 1150:1158 the lungs of xenografted mice treated with OGT-specific shRNA compared to those treated with non-targeting shRNA 1150:1261 Additionally, levels of E7 or OGT co-localized with Ki-67 were significantly decreased in the lungs of xenografted mice treated with OGT-specific shRNA compared to those treated with non-targeting shRNA. 27845045 6 1 theme expression 901:910 arg1 levels 912:917 significantly decreased expression levels 877:917 significantly decreased expression levels of E6, E7, and HCF-1 877:938 Western blotting and immunofluorescence analysis showed significantly decreased expression levels of E6, E7, and HCF-1 in the lungs of xenografted mice treated with an OGT-specific shRNA compared to those treated with non-targeting shRNA. 27845045 7 2 theme E7 1084:1085 arg1 levels 1074:1079 levels 1074:1079 levels of E7 or OGT co-localized with Ki-67 1074:1116 Additionally, levels of E7 or OGT co-localized with Ki-67 were significantly decreased in the lungs of xenografted mice treated with OGT-specific shRNA compared to those treated with non-targeting shRNA. 27845045 1 3 theme papilloma 163:171 arg1 HPV 180:182 HPV 180:182 HPV 180:182 High-risk human papilloma virus (HPV) 16/18 infections are often found in lung cancer. 27845045 1 3 theme papilloma 163:171 arg1 virus 173:177 human papilloma virus 157:177 High-risk human papilloma virus (HPV) 16/18 infections 147:200 High-risk human papilloma virus (HPV) 16/18 infections are often found in lung cancer. 27845045 4 4 theme chemokine 567:575 arg1 HPV 541:543 HPV 16/18 E6/E7, or C-X-C chemokine receptor type 4 (CXCR4) 541:599 HPV 16/18 E6/E7, or C-X-C chemokine receptor type 4 (CXCR4) 541:599 In the present study, we assessed the relationship between O-GlcNAc transferase (OGT) and HPV 16/18 E6/E7, or C-X-C chemokine receptor type 4 (CXCR4), in HeLa cells and in lungs of xenografted mice. 27845045 4 4 theme chemokine 567:575 arg1 type 586:589 16/18 E6/E7, or C-X-C chemokine receptor type 4 545:591 type 586:589 In the present study, we assessed the relationship between O-GlcNAc transferase (OGT) and HPV 16/18 E6/E7, or C-X-C chemokine receptor type 4 (CXCR4), in HeLa cells and in lungs of xenografted mice. 27845045 0 5 theme E6 102:103 arg1 spread 71:76 metastatic spread 60:76 metastatic spread of human papillomavirus E6 and E7 oncoproteins to the lungs of mice 60:144 O-linked-N-acetylglucosamine transferase is associated with metastatic spread of human papillomavirus E6 and E7 oncoproteins to the lungs of mice. 27845045 6 6 theme decreased 891:899 arg1 levels 912:917 significantly decreased expression levels 877:917 significantly decreased expression levels of E6, E7, and HCF-1 877:938 Western blotting and immunofluorescence analysis showed significantly decreased expression levels of E6, E7, and HCF-1 in the lungs of xenografted mice treated with an OGT-specific shRNA compared to those treated with non-targeting shRNA. 27845045 1 7 theme virus 173:177 arg1 infections 191:200 High-risk human papilloma virus (HPV) 16/18 infections 147:200 High-risk human papilloma virus (HPV) 16/18 infections 147:200 High-risk human papilloma virus (HPV) 16/18 infections are often found in lung cancer. 27845045 4 8 theme C-X-C 561:565 arg1 HPV 541:543 HPV 16/18 E6/E7, or C-X-C chemokine receptor type 4 (CXCR4) 541:599 HPV 16/18 E6/E7, or C-X-C chemokine receptor type 4 (CXCR4) 541:599 In the present study, we assessed the relationship between O-GlcNAc transferase (OGT) and HPV 16/18 E6/E7, or C-X-C chemokine receptor type 4 (CXCR4), in HeLa cells and in lungs of xenografted mice. 27845045 4 8 theme C-X-C 561:565 arg1 type 586:589 16/18 E6/E7, or C-X-C chemokine receptor type 4 545:591 type 586:589 In the present study, we assessed the relationship between O-GlcNAc transferase (OGT) and HPV 16/18 E6/E7, or C-X-C chemokine receptor type 4 (CXCR4), in HeLa cells and in lungs of xenografted mice. 27845045 0 9 theme oncoproteins 112:123 arg1 spread 71:76 metastatic spread 60:76 metastatic spread of human papillomavirus E6 and E7 oncoproteins to the lungs of mice 60:144 O-linked-N-acetylglucosamine transferase is associated with metastatic spread of human papillomavirus E6 and E7 oncoproteins to the lungs of mice. 27845045 9 10 theme HPV 1628:1630 arg1 cells 1653:1657 HPV E6/E7-positive tumor cells 1628:1657 HPV E6/E7-positive tumor cells 1628:1657 These findings provide novel evidence that OGT functions in metastatic spread of HPV E6/E7-positive tumor cells to the lungs through E6/E7, HCF-1 and CXCR4, suggesting OGT might be a therapeutic target for HPV-positive lung cancer. 27845045 6 11 theme Western 821:827 arg1 blotting 829:836 Western blotting 821:836 Western blotting 821:836 Western blotting and immunofluorescence analysis showed significantly decreased expression levels of E6, E7, and HCF-1 in the lungs of xenografted mice treated with an OGT-specific shRNA compared to those treated with non-targeting shRNA. 27845045 8 12 theme cells 1540:1544 arg1 adhesion 1485:1492 adhesion 1485:1492 adhesion 1485:1492 Moreover, levels of CXCR4 were significantly decreased in HeLa cells and in the lungs of xenografted mice treated with OGT-specific shRNA compared to those treated with non-targeting shRNA; this may be related to reduced adhesion or invasion of circulating HPV-positive tumor cells. 27845045 8 12 theme cells 1540:1544 arg1 invasion 1497:1504 invasion 1497:1504 invasion 1497:1504 Moreover, levels of CXCR4 were significantly decreased in HeLa cells and in the lungs of xenografted mice treated with OGT-specific shRNA compared to those treated with non-targeting shRNA; this may be related to reduced adhesion or invasion of circulating HPV-positive tumor cells. 27845045 0 13 theme E7 109:110 arg1 oncoproteins 112:123 human papillomavirus E6 and E7 oncoproteins 81:123 oncoproteins 112:123 O-linked-N-acetylglucosamine transferase is associated with metastatic spread of human papillomavirus E6 and E7 oncoproteins to the lungs of mice. 27845045 8 14 theme HeLa 1322:1325 arg1 cells 1327:1331 HeLa cells 1322:1331 HeLa cells 1322:1331 Moreover, levels of CXCR4 were significantly decreased in HeLa cells and in the lungs of xenografted mice treated with OGT-specific shRNA compared to those treated with non-targeting shRNA; this may be related to reduced adhesion or invasion of circulating HPV-positive tumor cells. 27845045 2 15 theme metastatic 274:283 arg1 spread 285:290 the metastatic spread 270:290 the metastatic spread of HPV-infected cervical cancer cells 270:328 The cellular mechanisms involved in the metastatic spread of HPV-infected cervical cancer cells remain largely elusive. 27845045 4 16 theme receptor 577:584 arg1 HPV 541:543 HPV 16/18 E6/E7, or C-X-C chemokine receptor type 4 (CXCR4) 541:599 HPV 16/18 E6/E7, or C-X-C chemokine receptor type 4 (CXCR4) 541:599 In the present study, we assessed the relationship between O-GlcNAc transferase (OGT) and HPV 16/18 E6/E7, or C-X-C chemokine receptor type 4 (CXCR4), in HeLa cells and in lungs of xenografted mice. 27845045 4 16 theme receptor 577:584 arg1 type 586:589 16/18 E6/E7, or C-X-C chemokine receptor type 4 545:591 type 586:589 In the present study, we assessed the relationship between O-GlcNAc transferase (OGT) and HPV 16/18 E6/E7, or C-X-C chemokine receptor type 4 (CXCR4), in HeLa cells and in lungs of xenografted mice. 27845045 8 17 theme reduced 1477:1483 arg1 adhesion 1485:1492 adhesion 1485:1492 adhesion 1485:1492 Moreover, levels of CXCR4 were significantly decreased in HeLa cells and in the lungs of xenografted mice treated with OGT-specific shRNA compared to those treated with non-targeting shRNA; this may be related to reduced adhesion or invasion of circulating HPV-positive tumor cells. 27845045 9 18 theme tumor 1647:1651 arg1 cells 1653:1657 HPV E6/E7-positive tumor cells 1628:1657 HPV E6/E7-positive tumor cells 1628:1657 These findings provide novel evidence that OGT functions in metastatic spread of HPV E6/E7-positive tumor cells to the lungs through E6/E7, HCF-1 and CXCR4, suggesting OGT might be a therapeutic target for HPV-positive lung cancer. 27845045 9 19 theme lung 1766:1769 arg1 cancer 1771:1776 HPV-positive lung cancer 1753:1776 HPV-positive lung cancer 1753:1776 These findings provide novel evidence that OGT functions in metastatic spread of HPV E6/E7-positive tumor cells to the lungs through E6/E7, HCF-1 and CXCR4, suggesting OGT might be a therapeutic target for HPV-positive lung cancer. 27845045 6 20 theme non-targeting 1039:1051 arg1 shRNA 1053:1057 non-targeting shRNA 1039:1057 non-targeting shRNA 1039:1057 Western blotting and immunofluorescence analysis showed significantly decreased expression levels of E6, E7, and HCF-1 in the lungs of xenografted mice treated with an OGT-specific shRNA compared to those treated with non-targeting shRNA. 27845045 3 21 theme High 354:357 arg1 modification 399:410 High O-linked-N-acetylglucosamine (O-GlcNAc) modification 354:410 High O-linked-N-acetylglucosamine (O-GlcNAc) modification 354:410 High O-linked-N-acetylglucosamine (O-GlcNAc) modification has also been observed in lung cancer. 27845045 6 22 theme immunofluorescence 842:859 arg1 analysis 861:868 immunofluorescence analysis 842:868 immunofluorescence analysis 842:868 Western blotting and immunofluorescence analysis showed significantly decreased expression levels of E6, E7, and HCF-1 in the lungs of xenografted mice treated with an OGT-specific shRNA compared to those treated with non-targeting shRNA. 27845045 6 23 theme xenografted 956:966 arg1 mice 968:971 xenografted mice 956:971 xenografted mice treated with an OGT-specific shRNA compared to those treated with non-targeting shRNA 956:1057 Western blotting and immunofluorescence analysis showed significantly decreased expression levels of E6, E7, and HCF-1 in the lungs of xenografted mice treated with an OGT-specific shRNA compared to those treated with non-targeting shRNA. 27845045 7 24 theme OGT 1090:1092 arg1 levels 1074:1079 levels 1074:1079 levels of E7 or OGT co-localized with Ki-67 1074:1116 Additionally, levels of E7 or OGT co-localized with Ki-67 were significantly decreased in the lungs of xenografted mice treated with OGT-specific shRNA compared to those treated with non-targeting shRNA. 27845045 5 25 theme xenograft 766:774 arg1 tumors 776:781 xenograft tumors 766:781 xenograft tumors 766:781 Depleting OGT with an OGT-specific shRNA significantly decreased levels of E6 and E7 oncoproteins in HeLa cells and xenograft tumors, and reduced tumor formation in vivo. 27845045 9 26 theme HPV-positive 1753:1764 arg1 cancer 1771:1776 HPV-positive lung cancer 1753:1776 HPV-positive lung cancer 1753:1776 These findings provide novel evidence that OGT functions in metastatic spread of HPV E6/E7-positive tumor cells to the lungs through E6/E7, HCF-1 and CXCR4, suggesting OGT might be a therapeutic target for HPV-positive lung cancer. 27845045 5 27 theme E7 732:733 arg1 levels 715:720 levels 715:720 levels of E6 and E7 oncoproteins 715:746 Depleting OGT with an OGT-specific shRNA significantly decreased levels of E6 and E7 oncoproteins in HeLa cells and xenograft tumors, and reduced tumor formation in vivo. 27845045 2 28 theme cancer 317:322 arg1 cells 324:328 HPV-infected cervical cancer cells 295:328 HPV-infected cervical cancer cells 295:328 The cellular mechanisms involved in the metastatic spread of HPV-infected cervical cancer cells remain largely elusive. 27845045 3 29 theme lung 438:441 arg1 cancer 443:448 lung cancer 438:448 lung cancer 438:448 High O-linked-N-acetylglucosamine (O-GlcNAc) modification has also been observed in lung cancer. 27845045 0 30 theme O-linked-N-acetylglucosamine 0:27 arg1 transferase 29:39 O-linked-N-acetylglucosamine transferase 0:39 O-linked-N-acetylglucosamine transferase 0:39 O-linked-N-acetylglucosamine transferase is associated with metastatic spread of human papillomavirus E6 and E7 oncoproteins to the lungs of mice. 27845045 8 31 theme circulating 1509:1519 arg1 cells 1540:1544 circulating HPV-positive tumor cells 1509:1544 circulating HPV-positive tumor cells 1509:1544 Moreover, levels of CXCR4 were significantly decreased in HeLa cells and in the lungs of xenografted mice treated with OGT-specific shRNA compared to those treated with non-targeting shRNA; this may be related to reduced adhesion or invasion of circulating HPV-positive tumor cells. 27845045 2 32 theme cervical 308:315 arg1 cells 324:328 HPV-infected cervical cancer cells 295:328 HPV-infected cervical cancer cells 295:328 The cellular mechanisms involved in the metastatic spread of HPV-infected cervical cancer cells remain largely elusive. 27845045 1 33 theme 16/18 185:189 arg1 infections 191:200 High-risk human papilloma virus (HPV) 16/18 infections 147:200 High-risk human papilloma virus (HPV) 16/18 infections 147:200 High-risk human papilloma virus (HPV) 16/18 infections are often found in lung cancer. 27845045 3 34 theme O-GlcNAc 389:396 arg1 modification 399:410 High O-linked-N-acetylglucosamine (O-GlcNAc) modification 354:410 High O-linked-N-acetylglucosamine (O-GlcNAc) modification 354:410 High O-linked-N-acetylglucosamine (O-GlcNAc) modification has also been observed in lung cancer. 27845045 6 35 theme HCF-1 934:938 arg1 levels 912:917 significantly decreased expression levels 877:917 significantly decreased expression levels of E6, E7, and HCF-1 877:938 Western blotting and immunofluorescence analysis showed significantly decreased expression levels of E6, E7, and HCF-1 in the lungs of xenografted mice treated with an OGT-specific shRNA compared to those treated with non-targeting shRNA. 27845045 9 36 theme cells 1653:1657 arg1 spread 1618:1623 metastatic spread 1607:1623 metastatic spread of HPV E6/E7-positive tumor cells to the lungs 1607:1670 These findings provide novel evidence that OGT functions in metastatic spread of HPV E6/E7-positive tumor cells to the lungs through E6/E7, HCF-1 and CXCR4, suggesting OGT might be a therapeutic target for HPV-positive lung cancer. 27845045 2 37 theme HPV-infected 295:306 arg1 cells 324:328 HPV-infected cervical cancer cells 295:328 HPV-infected cervical cancer cells 295:328 The cellular mechanisms involved in the metastatic spread of HPV-infected cervical cancer cells remain largely elusive. 27845045 8 38 theme tumor 1534:1538 arg1 cells 1540:1544 circulating HPV-positive tumor cells 1509:1544 circulating HPV-positive tumor cells 1509:1544 Moreover, levels of CXCR4 were significantly decreased in HeLa cells and in the lungs of xenografted mice treated with OGT-specific shRNA compared to those treated with non-targeting shRNA; this may be related to reduced adhesion or invasion of circulating HPV-positive tumor cells. 27845045 4 39 theme present 458:464 arg1 study 466:470 the present study 454:470 the present study 454:470 In the present study, we assessed the relationship between O-GlcNAc transferase (OGT) and HPV 16/18 E6/E7, or C-X-C chemokine receptor type 4 (CXCR4), in HeLa cells and in lungs of xenografted mice. 27845045 9 40 theme therapeutic 1730:1740 arg1 target 1742:1747 a therapeutic target 1728:1747 a therapeutic target for HPV-positive lung cancer 1728:1776 These findings provide novel evidence that OGT functions in metastatic spread of HPV E6/E7-positive tumor cells to the lungs through E6/E7, HCF-1 and CXCR4, suggesting OGT might be a therapeutic target for HPV-positive lung cancer. 27845045 9 40 theme therapeutic 1730:1740 arg1 OGT 1715:1717 OGT 1715:1717 OGT 1715:1717 These findings provide novel evidence that OGT functions in metastatic spread of HPV E6/E7-positive tumor cells to the lungs through E6/E7, HCF-1 and CXCR4, suggesting OGT might be a therapeutic target for HPV-positive lung cancer. 27845045 4 41 theme mice 644:647 arg1 lungs 623:627 lungs 623:627 lungs of xenografted mice 623:647 In the present study, we assessed the relationship between O-GlcNAc transferase (OGT) and HPV 16/18 E6/E7, or C-X-C chemokine receptor type 4 (CXCR4), in HeLa cells and in lungs of xenografted mice. 27845045 0 42 theme metastatic 60:69 arg1 spread 71:76 metastatic spread 60:76 metastatic spread of human papillomavirus E6 and E7 oncoproteins to the lungs of mice 60:144 O-linked-N-acetylglucosamine transferase is associated with metastatic spread of human papillomavirus E6 and E7 oncoproteins to the lungs of mice. 27845045 8 43 theme HPV-positive 1521:1532 arg1 cells 1540:1544 circulating HPV-positive tumor cells 1509:1544 circulating HPV-positive tumor cells 1509:1544 Moreover, levels of CXCR4 were significantly decreased in HeLa cells and in the lungs of xenografted mice treated with OGT-specific shRNA compared to those treated with non-targeting shRNA; this may be related to reduced adhesion or invasion of circulating HPV-positive tumor cells. 27845045 3 44 located observed 426:433 arg1 cancer 443:448 lung cancer 438:448 lung cancer 438:448 High O-linked-N-acetylglucosamine (O-GlcNAc) modification has also been observed in lung cancer. 27845045 3 44 located observed 426:433 arg2 modification 399:410 High O-linked-N-acetylglucosamine (O-GlcNAc) modification 354:410 High O-linked-N-acetylglucosamine (O-GlcNAc) modification 354:410 High O-linked-N-acetylglucosamine (O-GlcNAc) modification has also been observed in lung cancer. 27845045 8 45 theme xenografted 1353:1363 arg1 mice 1365:1368 xenografted mice 1353:1368 xenografted mice treated with OGT-specific shRNA compared to those treated with non-targeting shRNA 1353:1451 Moreover, levels of CXCR4 were significantly decreased in HeLa cells and in the lungs of xenografted mice treated with OGT-specific shRNA compared to those treated with non-targeting shRNA; this may be related to reduced adhesion or invasion of circulating HPV-positive tumor cells. 27845045 5 46 theme tumor 796:800 arg1 formation 802:810 tumor formation 796:810 tumor formation 796:810 Depleting OGT with an OGT-specific shRNA significantly decreased levels of E6 and E7 oncoproteins in HeLa cells and xenograft tumors, and reduced tumor formation in vivo. 27845045 6 47 theme E7 926:927 arg1 levels 912:917 significantly decreased expression levels 877:917 significantly decreased expression levels of E6, E7, and HCF-1 877:938 Western blotting and immunofluorescence analysis showed significantly decreased expression levels of E6, E7, and HCF-1 in the lungs of xenografted mice treated with an OGT-specific shRNA compared to those treated with non-targeting shRNA. 27845045 0 48 theme mice 141:144 arg1 lungs 132:136 the lungs 128:136 the lungs of mice 128:144 O-linked-N-acetylglucosamine transferase is associated with metastatic spread of human papillomavirus E6 and E7 oncoproteins to the lungs of mice. 27845045 9 49 theme E6/E7-positive 1632:1645 arg1 cells 1653:1657 HPV E6/E7-positive tumor cells 1628:1657 HPV E6/E7-positive tumor cells 1628:1657 These findings provide novel evidence that OGT functions in metastatic spread of HPV E6/E7-positive tumor cells to the lungs through E6/E7, HCF-1 and CXCR4, suggesting OGT might be a therapeutic target for HPV-positive lung cancer. 27845045 9 50 theme novel 1570:1574 arg1 evidence 1576:1583 novel evidence that OGT functions in metastatic spread of HPV E6/E7-positive tumor cells to the lungs through E6/E7, HCF-1 and CXCR4, suggesting OGT might be a therapeutic target for HPV-positive lung cancer 1570:1776 novel evidence that OGT functions in metastatic spread of HPV E6/E7-positive tumor cells to the lungs through E6/E7, HCF-1 and CXCR4, suggesting OGT might be a therapeutic target for HPV-positive lung cancer 1570:1776 These findings provide novel evidence that OGT functions in metastatic spread of HPV E6/E7-positive tumor cells to the lungs through E6/E7, HCF-1 and CXCR4, suggesting OGT might be a therapeutic target for HPV-positive lung cancer. 27845045 4 51 theme HeLa 605:608 arg1 cells 610:614 HeLa cells 605:614 HeLa cells 605:614 In the present study, we assessed the relationship between O-GlcNAc transferase (OGT) and HPV 16/18 E6/E7, or C-X-C chemokine receptor type 4 (CXCR4), in HeLa cells and in lungs of xenografted mice. 27845045 5 52 theme HeLa 751:754 arg1 cells 756:760 HeLa cells 751:760 HeLa cells 751:760 Depleting OGT with an OGT-specific shRNA significantly decreased levels of E6 and E7 oncoproteins in HeLa cells and xenograft tumors, and reduced tumor formation in vivo. 27845045 3 53 theme O-linked-N-acetylglucosamine 359:386 arg1 modification 399:410 High O-linked-N-acetylglucosamine (O-GlcNAc) modification 354:410 High O-linked-N-acetylglucosamine (O-GlcNAc) modification 354:410 High O-linked-N-acetylglucosamine (O-GlcNAc) modification has also been observed in lung cancer. 27845045 5 54 theme E6 725:726 arg1 levels 715:720 levels 715:720 levels of E6 and E7 oncoproteins 715:746 Depleting OGT with an OGT-specific shRNA significantly decreased levels of E6 and E7 oncoproteins in HeLa cells and xenograft tumors, and reduced tumor formation in vivo. 27845045 7 55 theme non-targeting 1243:1255 arg1 shRNA 1257:1261 non-targeting shRNA 1243:1261 non-targeting shRNA 1243:1261 Additionally, levels of E7 or OGT co-localized with Ki-67 were significantly decreased in the lungs of xenografted mice treated with OGT-specific shRNA compared to those treated with non-targeting shRNA. 27845045 5 56 theme OGT-specific 672:683 arg1 shRNA 685:689 an OGT-specific shRNA 669:689 an OGT-specific shRNA 669:689 Depleting OGT with an OGT-specific shRNA significantly decreased levels of E6 and E7 oncoproteins in HeLa cells and xenograft tumors, and reduced tumor formation in vivo. 27845045 6 57 theme E6 922:923 arg1 levels 912:917 significantly decreased expression levels 877:917 significantly decreased expression levels of E6, E7, and HCF-1 877:938 Western blotting and immunofluorescence analysis showed significantly decreased expression levels of E6, E7, and HCF-1 in the lungs of xenografted mice treated with an OGT-specific shRNA compared to those treated with non-targeting shRNA. 27845045 4 58 dep HPV 541:543 arg1 E6/E7 551:555 16/18 E6/E7, or C-X-C chemokine receptor type 4 545:591 E6/E7 551:555 In the present study, we assessed the relationship between O-GlcNAc transferase (OGT) and HPV 16/18 E6/E7, or C-X-C chemokine receptor type 4 (CXCR4), in HeLa cells and in lungs of xenografted mice. 27845045 4 58 dep HPV 541:543 arg1 type 586:589 16/18 E6/E7, or C-X-C chemokine receptor type 4 545:591 type 586:589 In the present study, we assessed the relationship between O-GlcNAc transferase (OGT) and HPV 16/18 E6/E7, or C-X-C chemokine receptor type 4 (CXCR4), in HeLa cells and in lungs of xenografted mice. 27845045 4 58 dep HPV 541:543 arg1 CXCR4 594:598 CXCR4 594:598 CXCR4 594:598 In the present study, we assessed the relationship between O-GlcNAc transferase (OGT) and HPV 16/18 E6/E7, or C-X-C chemokine receptor type 4 (CXCR4), in HeLa cells and in lungs of xenografted mice. 27845045 4 58 dep HPV 541:543 arg1 HPV 541:543 HPV 16/18 E6/E7, or C-X-C chemokine receptor type 4 (CXCR4) 541:599 HPV 16/18 E6/E7, or C-X-C chemokine receptor type 4 (CXCR4) 541:599 In the present study, we assessed the relationship between O-GlcNAc transferase (OGT) and HPV 16/18 E6/E7, or C-X-C chemokine receptor type 4 (CXCR4), in HeLa cells and in lungs of xenografted mice. 27845045 8 59 theme mice 1365:1368 arg1 lungs 1344:1348 the lungs 1340:1348 the lungs of xenografted mice treated with OGT-specific shRNA compared to those treated with non-targeting shRNA 1340:1451 Moreover, levels of CXCR4 were significantly decreased in HeLa cells and in the lungs of xenografted mice treated with OGT-specific shRNA compared to those treated with non-targeting shRNA; this may be related to reduced adhesion or invasion of circulating HPV-positive tumor cells. 27845045 7 60 theme xenografted 1163:1173 arg1 mice 1175:1178 xenografted mice 1163:1178 xenografted mice treated with OGT-specific shRNA compared to those treated with non-targeting shRNA 1163:1261 Additionally, levels of E7 or OGT co-localized with Ki-67 were significantly decreased in the lungs of xenografted mice treated with OGT-specific shRNA compared to those treated with non-targeting shRNA. 27845045 5 61 dep E6 725:726 arg1 oncoproteins 735:746 oncoproteins 735:746 oncoproteins 735:746 Depleting OGT with an OGT-specific shRNA significantly decreased levels of E6 and E7 oncoproteins in HeLa cells and xenograft tumors, and reduced tumor formation in vivo. 27845045 8 62 theme non-targeting 1433:1445 arg1 shRNA 1447:1451 non-targeting shRNA 1433:1451 non-targeting shRNA 1433:1451 Moreover, levels of CXCR4 were significantly decreased in HeLa cells and in the lungs of xenografted mice treated with OGT-specific shRNA compared to those treated with non-targeting shRNA; this may be related to reduced adhesion or invasion of circulating HPV-positive tumor cells. 27845045 8 63 theme OGT-specific 1383:1394 arg1 shRNA 1396:1400 OGT-specific shRNA 1383:1400 OGT-specific shRNA 1383:1400 Moreover, levels of CXCR4 were significantly decreased in HeLa cells and in the lungs of xenografted mice treated with OGT-specific shRNA compared to those treated with non-targeting shRNA; this may be related to reduced adhesion or invasion of circulating HPV-positive tumor cells. 27845045 4 64 theme xenografted 632:642 arg1 mice 644:647 xenografted mice 632:647 xenografted mice 632:647 In the present study, we assessed the relationship between O-GlcNAc transferase (OGT) and HPV 16/18 E6/E7, or C-X-C chemokine receptor type 4 (CXCR4), in HeLa cells and in lungs of xenografted mice. 27845045 5 65 theme Depleting 650:658 arg1 OGT 660:662 Depleting OGT 650:662 Depleting OGT with an OGT-specific shRNA 650:689 Depleting OGT with an OGT-specific shRNA significantly decreased levels of E6 and E7 oncoproteins in HeLa cells and xenograft tumors, and reduced tumor formation in vivo. 27845045 1 66 located found 212:216 arg1 cancer 226:231 lung cancer 221:231 lung cancer 221:231 High-risk human papilloma virus (HPV) 16/18 infections are often found in lung cancer. 27845045 1 66 located found 212:216 arg2 infections 191:200 High-risk human papilloma virus (HPV) 16/18 infections 147:200 High-risk human papilloma virus (HPV) 16/18 infections 147:200 High-risk human papilloma virus (HPV) 16/18 infections are often found in lung cancer. 27845045 8 67 theme CXCR4 1284:1288 arg1 levels 1274:1279 levels 1274:1279 levels of CXCR4 1274:1288 Moreover, levels of CXCR4 were significantly decreased in HeLa cells and in the lungs of xenografted mice treated with OGT-specific shRNA compared to those treated with non-targeting shRNA; this may be related to reduced adhesion or invasion of circulating HPV-positive tumor cells. 27845045 2 68 theme cells 324:328 arg1 spread 285:290 the metastatic spread 270:290 the metastatic spread of HPV-infected cervical cancer cells 270:328 The cellular mechanisms involved in the metastatic spread of HPV-infected cervical cancer cells remain largely elusive. 27845045 1 69 theme lung 221:224 arg1 cancer 226:231 lung cancer 221:231 lung cancer 221:231 High-risk human papilloma virus (HPV) 16/18 infections are often found in lung cancer. 27845045 0 70 theme papillomavirus 87:100 arg1 E6 102:103 human papillomavirus E6 and E7 oncoproteins 81:123 E6 102:103 O-linked-N-acetylglucosamine transferase is associated with metastatic spread of human papillomavirus E6 and E7 oncoproteins to the lungs of mice. 27845045 6 71 theme OGT-specific 989:1000 arg1 shRNA 1002:1006 an OGT-specific shRNA 986:1006 an OGT-specific shRNA compared to those treated with non-targeting shRNA 986:1057 Western blotting and immunofluorescence analysis showed significantly decreased expression levels of E6, E7, and HCF-1 in the lungs of xenografted mice treated with an OGT-specific shRNA compared to those treated with non-targeting shRNA. 27845045 2 72 theme cellular 238:245 arg1 mechanisms 247:256 The cellular mechanisms 234:256 The cellular mechanisms involved in the metastatic spread of HPV-infected cervical cancer cells 234:328 The cellular mechanisms involved in the metastatic spread of HPV-infected cervical cancer cells remain largely elusive. 27845045 1 73 theme High-risk 147:155 arg1 infections 191:200 High-risk human papilloma virus (HPV) 16/18 infections 147:200 High-risk human papilloma virus (HPV) 16/18 infections 147:200 High-risk human papilloma virus (HPV) 16/18 infections are often found in lung cancer. 27845045 7 74 theme OGT-specific 1193:1204 arg1 shRNA 1206:1210 OGT-specific shRNA 1193:1210 OGT-specific shRNA 1193:1210 Additionally, levels of E7 or OGT co-localized with Ki-67 were significantly decreased in the lungs of xenografted mice treated with OGT-specific shRNA compared to those treated with non-targeting shRNA. 27845045 0 75 theme human 81:85 arg1 E6 102:103 human papillomavirus E6 and E7 oncoproteins 81:123 E6 102:103 O-linked-N-acetylglucosamine transferase is associated with metastatic spread of human papillomavirus E6 and E7 oncoproteins to the lungs of mice. 27845045 4 76 theme O-GlcNAc 510:517 arg1 OGT 532:534 OGT 532:534 OGT 532:534 In the present study, we assessed the relationship between O-GlcNAc transferase (OGT) and HPV 16/18 E6/E7, or C-X-C chemokine receptor type 4 (CXCR4), in HeLa cells and in lungs of xenografted mice. 27845045 4 76 theme O-GlcNAc 510:517 arg1 transferase 519:529 O-GlcNAc transferase 510:529 O-GlcNAc transferase (OGT) 510:535 In the present study, we assessed the relationship between O-GlcNAc transferase (OGT) and HPV 16/18 E6/E7, or C-X-C chemokine receptor type 4 (CXCR4), in HeLa cells and in lungs of xenografted mice. 27845045 9 77 theme metastatic 1607:1616 arg1 spread 1618:1623 metastatic spread 1607:1623 metastatic spread of HPV E6/E7-positive tumor cells to the lungs 1607:1670 These findings provide novel evidence that OGT functions in metastatic spread of HPV E6/E7-positive tumor cells to the lungs through E6/E7, HCF-1 and CXCR4, suggesting OGT might be a therapeutic target for HPV-positive lung cancer. 27845045 5 78 with OGT 660:662 arg1 shRNA 685:689 an OGT-specific shRNA 669:689 an OGT-specific shRNA 669:689 Depleting OGT with an OGT-specific shRNA significantly decreased levels of E6 and E7 oncoproteins in HeLa cells and xenograft tumors, and reduced tumor formation in vivo. 27845045 1 79 theme human 157:161 arg1 HPV 180:182 HPV 180:182 HPV 180:182 High-risk human papilloma virus (HPV) 16/18 infections are often found in lung cancer. 27845045 1 79 theme human 157:161 arg1 virus 173:177 human papilloma virus 157:177 High-risk human papilloma virus (HPV) 16/18 infections 147:200 High-risk human papilloma virus (HPV) 16/18 infections are often found in lung cancer. 27845045 6 80 theme mice 968:971 arg1 lungs 947:951 the lungs 943:951 the lungs of xenografted mice treated with an OGT-specific shRNA compared to those treated with non-targeting shRNA 943:1057 Western blotting and immunofluorescence analysis showed significantly decreased expression levels of E6, E7, and HCF-1 in the lungs of xenografted mice treated with an OGT-specific shRNA compared to those treated with non-targeting shRNA. 27629714 7 0 theme axonal 1275:1280 arg1 integrity 1282:1290 axonal integrity 1275:1290 axonal integrity 1275:1290 Furthermore, phenotypes of OGT-SCKO and Prx-deficient mice are very similar, suggesting that metabolic control of PRX O-GlcNAcylation is crucial for myelin maintenance and axonal integrity. 27629714 3 1 theme O-linked 527:534 arg1 addition 536:543 the O-linked addition 523:543 the O-linked addition of N-acetylglucosamine (GlcNAc) moieties to Ser and Thr residues 523:608 To further interrogate this metabolic influence on axon-glial interactions, we generated OGT-SCKO mice with SC-specific deletion of the metabolic/nutrient sensing protein O-GlcNAc transferase that mediates the O-linked addition of N-acetylglucosamine (GlcNAc) moieties to Ser and Thr residues. 27629714 10 2 theme tomaculous 1611:1620 arg1 neuropathy 1636:1645 a tomaculous demyelinating neuropathy 1609:1645 a tomaculous demyelinating neuropathy accompanied with progressive axon degeneration and motor and sensory nerve dysfunction 1609:1732 SC-specific deletion of OGT (OGT-SCKO mice) causes a tomaculous demyelinating neuropathy accompanied with progressive axon degeneration and motor and sensory nerve dysfunction. 27629714 7 3 theme Prx-deficient 1143:1155 arg1 mice 1157:1160 OGT-SCKO and Prx-deficient mice 1130:1160 OGT-SCKO and Prx-deficient mice 1130:1160 Furthermore, phenotypes of OGT-SCKO and Prx-deficient mice are very similar, suggesting that metabolic control of PRX O-GlcNAcylation is crucial for myelin maintenance and axonal integrity. 27629714 7 4 theme OGT-SCKO 1130:1137 arg1 mice 1157:1160 OGT-SCKO and Prx-deficient mice 1130:1160 OGT-SCKO and Prx-deficient mice 1130:1160 Furthermore, phenotypes of OGT-SCKO and Prx-deficient mice are very similar, suggesting that metabolic control of PRX O-GlcNAcylation is crucial for myelin maintenance and axonal integrity. 27629714 1 5 theme nervous 158:164 arg1 system 166:171 the peripheral nervous system 143:171 the peripheral nervous system 143:171 UNLABELLED Schwann cells (SCs), ensheathing glia of the peripheral nervous system, support axonal survival and function. 27629714 11 6 from neuropathy 1814:1823 arg1 humans 1828:1833 humans 1828:1833 humans 1828:1833 We also found Periaxin (PRX), a myelin protein whose mutation causes inherited neuropathy in humans, is O-GlcNAcylated. 27629714 5 7 theme O-GlcNAcylated 866:879 arg1 proteins 881:888 more than 100 O-GlcNAcylated proteins 852:888 more than 100 O-GlcNAcylated proteins 852:888 Proteomic analysis identified more than 100 O-GlcNAcylated proteins in rat sciatic nerve, including Periaxin (PRX), a myelin protein whose mutation causes inherited neuropathy in humans. 27629714 5 7 theme O-GlcNAcylated 866:879 arg1 Periaxin 922:929 Periaxin 922:929 Periaxin (PRX) 922:935 Proteomic analysis identified more than 100 O-GlcNAcylated proteins in rat sciatic nerve, including Periaxin (PRX), a myelin protein whose mutation causes inherited neuropathy in humans. 27629714 8 8 link O-linked 1400:1407 arg1 GlcNAc 1430:1435 GlcNAc 1430:1435 GlcNAc 1430:1435 SIGNIFICANCE STATEMENT The nutrient sensing protein O-GlcNAc transferase (OGT) mediates post-translational O-linked N-acetylglucosamine (GlcNAc) modification. 27629714 8 8 link O-linked 1400:1407 arg1 N-acetylglucosamine 1409:1427 O-linked N-acetylglucosamine 1400:1427 post-translational O-linked N-acetylglucosamine (GlcNAc) modification 1381:1449 SIGNIFICANCE STATEMENT The nutrient sensing protein O-GlcNAc transferase (OGT) mediates post-translational O-linked N-acetylglucosamine (GlcNAc) modification. 27629714 13 9 theme SC 2186:2187 arg1 function 2189:2196 SC function 2186:2196 SC function 2186:2196 This study will be useful in understanding how SC metabolism contributes to PNS function and in developing new strategies for treating peripheral neuropathy by targeting SC function. 27629714 5 10 from proteins 881:888 arg1 nerve 905:909 rat sciatic nerve 893:909 rat sciatic nerve 893:909 Proteomic analysis identified more than 100 O-GlcNAcylated proteins in rat sciatic nerve, including Periaxin (PRX), a myelin protein whose mutation causes inherited neuropathy in humans. 27629714 12 11 theme mice 2010:2013 arg1 neuropathy 1987:1996 the neuropathy 1983:1996 the neuropathy of OGT-SCKO mice 1983:2013 Importantly, phenotypes of OGT-SCKO and Prx mutant mice are very similar, implying that compromised PRX function contributes to the neuropathy of OGT-SCKO mice. 27629714 8 12 theme O-GlcNAc 1345:1352 arg1 transferase 1354:1364 protein O-GlcNAc transferase 1337:1364 The nutrient sensing protein O-GlcNAc transferase (OGT) 1316:1370 SIGNIFICANCE STATEMENT The nutrient sensing protein O-GlcNAc transferase (OGT) mediates post-translational O-linked N-acetylglucosamine (GlcNAc) modification. 27629714 8 12 theme O-GlcNAc 1345:1352 arg1 OGT 1367:1369 OGT 1367:1369 OGT 1367:1369 SIGNIFICANCE STATEMENT The nutrient sensing protein O-GlcNAc transferase (OGT) mediates post-translational O-linked N-acetylglucosamine (GlcNAc) modification. 27629714 10 13 theme axon 1676:1679 arg1 degeneration 1681:1692 progressive axon degeneration 1664:1692 progressive axon degeneration 1664:1692 SC-specific deletion of OGT (OGT-SCKO mice) causes a tomaculous demyelinating neuropathy accompanied with progressive axon degeneration and motor and sensory nerve dysfunction. 27629714 9 14 theme axonal 1545:1550 arg1 loss 1552:1555 axonal loss 1545:1555 axonal loss 1545:1555 Here we find that OGT functions in Schwann cells (SCs) to maintain normal myelin and prevent axonal loss. 27629714 4 15 theme demyelination 753:765 arg1 thickenings 696:706 focal thickenings 690:706 focal thickenings of the myelin sheath (tomacula), progressive demyelination, axonal loss, and motor and sensory nerve dysfunction 690:819 The OGT-SCKO mice develop tomaculous demyelinating neuropathy characterized by focal thickenings of the myelin sheath (tomacula), progressive demyelination, axonal loss, and motor and sensory nerve dysfunction. 27629714 13 16 theme peripheral 2151:2160 arg1 neuropathy 2162:2171 peripheral neuropathy 2151:2171 peripheral neuropathy 2151:2171 This study will be useful in understanding how SC metabolism contributes to PNS function and in developing new strategies for treating peripheral neuropathy by targeting SC function. 27629714 5 17 theme myelin 940:945 arg1 protein 947:953 a myelin protein 938:953 a myelin protein whose mutation causes inherited neuropathy in humans 938:1006 Proteomic analysis identified more than 100 O-GlcNAcylated proteins in rat sciatic nerve, including Periaxin (PRX), a myelin protein whose mutation causes inherited neuropathy in humans. 27629714 5 17 theme myelin 940:945 arg1 Periaxin 922:929 Periaxin 922:929 Periaxin (PRX) 922:935 Proteomic analysis identified more than 100 O-GlcNAcylated proteins in rat sciatic nerve, including Periaxin (PRX), a myelin protein whose mutation causes inherited neuropathy in humans. 27629714 4 18 theme sheath 722:727 arg1 thickenings 696:706 focal thickenings 690:706 focal thickenings of the myelin sheath (tomacula), progressive demyelination, axonal loss, and motor and sensory nerve dysfunction 690:819 The OGT-SCKO mice develop tomaculous demyelinating neuropathy characterized by focal thickenings of the myelin sheath (tomacula), progressive demyelination, axonal loss, and motor and sensory nerve dysfunction. 27629714 0 19 theme O-GlcNAc 13:20 arg1 Glycosylation 22:34 Schwann Cell O-GlcNAc Glycosylation 0:34 Schwann Cell O-GlcNAc Glycosylation 0:34 Schwann Cell O-GlcNAc Glycosylation Is Required for Myelin Maintenance and Axon Integrity. 27629714 8 20 theme post-translational 1381:1398 arg1 modification 1438:1449 post-translational O-linked N-acetylglucosamine (GlcNAc) modification 1381:1449 post-translational O-linked N-acetylglucosamine (GlcNAc) modification 1381:1449 SIGNIFICANCE STATEMENT The nutrient sensing protein O-GlcNAc transferase (OGT) mediates post-translational O-linked N-acetylglucosamine (GlcNAc) modification. 27629714 0 21 theme Axon 75:78 arg1 Integrity 80:88 Axon Integrity 75:88 Axon Integrity 75:88 Schwann Cell O-GlcNAc Glycosylation Is Required for Myelin Maintenance and Axon Integrity. 27629714 13 22 theme new 2123:2125 arg1 strategies 2127:2136 new strategies 2123:2136 new strategies for treating peripheral neuropathy by targeting SC function 2123:2196 This study will be useful in understanding how SC metabolism contributes to PNS function and in developing new strategies for treating peripheral neuropathy by targeting SC function. 27629714 3 23 theme metabolic 345:353 arg1 influence 355:363 this metabolic influence 340:363 this metabolic influence on axon-glial interactions 340:390 To further interrogate this metabolic influence on axon-glial interactions, we generated OGT-SCKO mice with SC-specific deletion of the metabolic/nutrient sensing protein O-GlcNAc transferase that mediates the O-linked addition of N-acetylglucosamine (GlcNAc) moieties to Ser and Thr residues. 27629714 4 24 theme motor 785:789 arg1 dysfunction 809:819 motor and sensory nerve dysfunction 785:819 dysfunction 809:819 The OGT-SCKO mice develop tomaculous demyelinating neuropathy characterized by focal thickenings of the myelin sheath (tomacula), progressive demyelination, axonal loss, and motor and sensory nerve dysfunction. 27629714 4 25 theme sensory 795:801 arg1 dysfunction 809:819 motor and sensory nerve dysfunction 785:819 dysfunction 809:819 The OGT-SCKO mice develop tomaculous demyelinating neuropathy characterized by focal thickenings of the myelin sheath (tomacula), progressive demyelination, axonal loss, and motor and sensory nerve dysfunction. 27629714 7 26 theme O-GlcNAcylation 1221:1235 arg1 control 1206:1212 metabolic control 1196:1212 metabolic control of PRX O-GlcNAcylation 1196:1235 Furthermore, phenotypes of OGT-SCKO and Prx-deficient mice are very similar, suggesting that metabolic control of PRX O-GlcNAcylation is crucial for myelin maintenance and axonal integrity. 27629714 4 27 theme axonal 768:773 arg1 loss 775:778 axonal loss 768:778 axonal loss 768:778 The OGT-SCKO mice develop tomaculous demyelinating neuropathy characterized by focal thickenings of the myelin sheath (tomacula), progressive demyelination, axonal loss, and motor and sensory nerve dysfunction. 27629714 10 28 theme sensory 1708:1714 arg1 dysfunction 1722:1732 motor and sensory nerve dysfunction 1698:1732 dysfunction 1722:1732 SC-specific deletion of OGT (OGT-SCKO mice) causes a tomaculous demyelinating neuropathy accompanied with progressive axon degeneration and motor and sensory nerve dysfunction. 27629714 0 29 theme Schwann 0:6 arg1 Glycosylation 22:34 Schwann Cell O-GlcNAc Glycosylation 0:34 Schwann Cell O-GlcNAc Glycosylation 0:34 Schwann Cell O-GlcNAc Glycosylation Is Required for Myelin Maintenance and Axon Integrity. 27629714 12 30 theme compromised 1943:1953 arg1 function 1959:1966 compromised PRX function 1943:1966 compromised PRX function 1943:1966 Importantly, phenotypes of OGT-SCKO and Prx mutant mice are very similar, implying that compromised PRX function contributes to the neuropathy of OGT-SCKO mice. 27629714 1 31 theme UNLABELLED 91:100 arg1 glia 135:138 ensheathing glia 123:138 ensheathing glia of the peripheral nervous system 123:171 UNLABELLED Schwann cells (SCs), ensheathing glia of the peripheral nervous system, support axonal survival and function. 27629714 1 31 theme UNLABELLED 91:100 arg1 SCs 117:119 SCs 117:119 SCs 117:119 UNLABELLED Schwann cells (SCs), ensheathing glia of the peripheral nervous system, support axonal survival and function. 27629714 1 31 theme UNLABELLED 91:100 arg1 cells 110:114 UNLABELLED Schwann cells 91:114 UNLABELLED Schwann cells (SCs) 91:120 UNLABELLED Schwann cells (SCs), ensheathing glia of the peripheral nervous system, support axonal survival and function. 27629714 6 32 theme mutant 1087:1092 arg1 animals 1094:1100 these mutant animals 1081:1100 these mutant animals 1081:1100 PRX lacking O-GlcNAcylation is mislocalized within the myelin sheath of these mutant animals. 27629714 3 33 theme sensing 472:478 arg1 transferase 497:507 the metabolic/nutrient sensing protein O-GlcNAc transferase 449:507 the metabolic/nutrient sensing protein O-GlcNAc transferase that mediates the O-linked addition of N-acetylglucosamine (GlcNAc) moieties to Ser and Thr residues 449:608 To further interrogate this metabolic influence on axon-glial interactions, we generated OGT-SCKO mice with SC-specific deletion of the metabolic/nutrient sensing protein O-GlcNAc transferase that mediates the O-linked addition of N-acetylglucosamine (GlcNAc) moieties to Ser and Thr residues. 27629714 7 34 theme metabolic 1196:1204 arg1 control 1206:1212 metabolic control 1196:1212 metabolic control of PRX O-GlcNAcylation 1196:1235 Furthermore, phenotypes of OGT-SCKO and Prx-deficient mice are very similar, suggesting that metabolic control of PRX O-GlcNAcylation is crucial for myelin maintenance and axonal integrity. 27629714 3 35 theme OGT-SCKO 406:413 arg1 mice 415:418 OGT-SCKO mice 406:418 OGT-SCKO mice with SC-specific deletion of the metabolic/nutrient sensing protein O-GlcNAc transferase that mediates the O-linked addition of N-acetylglucosamine (GlcNAc) moieties to Ser and Thr residues 406:608 To further interrogate this metabolic influence on axon-glial interactions, we generated OGT-SCKO mice with SC-specific deletion of the metabolic/nutrient sensing protein O-GlcNAc transferase that mediates the O-linked addition of N-acetylglucosamine (GlcNAc) moieties to Ser and Thr residues. 27629714 5 36 theme rat 893:895 arg1 nerve 905:909 rat sciatic nerve 893:909 rat sciatic nerve 893:909 Proteomic analysis identified more than 100 O-GlcNAcylated proteins in rat sciatic nerve, including Periaxin (PRX), a myelin protein whose mutation causes inherited neuropathy in humans. 27629714 6 37 theme myelin 1064:1069 arg1 sheath 1071:1076 the myelin sheath 1060:1076 the myelin sheath of these mutant animals 1060:1100 PRX lacking O-GlcNAcylation is mislocalized within the myelin sheath of these mutant animals. 27629714 10 38 theme OGT 1582:1584 arg1 deletion 1570:1577 SC-specific deletion 1558:1577 SC-specific deletion of OGT (OGT-SCKO mice) 1558:1600 SC-specific deletion of OGT (OGT-SCKO mice) causes a tomaculous demyelinating neuropathy accompanied with progressive axon degeneration and motor and sensory nerve dysfunction. 27629714 13 39 theme SC 2063:2064 arg1 metabolism 2066:2075 SC metabolism 2063:2075 SC metabolism 2063:2075 This study will be useful in understanding how SC metabolism contributes to PNS function and in developing new strategies for treating peripheral neuropathy by targeting SC function. 27629714 5 40 theme Proteomic 822:830 arg1 analysis 832:839 Proteomic analysis 822:839 Proteomic analysis 822:839 Proteomic analysis identified more than 100 O-GlcNAcylated proteins in rat sciatic nerve, including Periaxin (PRX), a myelin protein whose mutation causes inherited neuropathy in humans. 27629714 12 41 theme OGT-SCKO 1882:1889 arg1 mice 1906:1909 OGT-SCKO and Prx mutant mice 1882:1909 OGT-SCKO and Prx mutant mice 1882:1909 Importantly, phenotypes of OGT-SCKO and Prx mutant mice are very similar, implying that compromised PRX function contributes to the neuropathy of OGT-SCKO mice. 27629714 2 42 theme SC 229:230 arg1 metabolism 232:241 SC metabolism 229:241 SC metabolism 229:241 Abnormalities in SC metabolism affect their ability to provide this support and maintain axon integrity. 27629714 4 43 theme dysfunction 809:819 arg1 thickenings 696:706 focal thickenings 690:706 focal thickenings of the myelin sheath (tomacula), progressive demyelination, axonal loss, and motor and sensory nerve dysfunction 690:819 The OGT-SCKO mice develop tomaculous demyelinating neuropathy characterized by focal thickenings of the myelin sheath (tomacula), progressive demyelination, axonal loss, and motor and sensory nerve dysfunction. 27629714 3 44 theme O-GlcNAc 488:495 arg1 transferase 497:507 the metabolic/nutrient sensing protein O-GlcNAc transferase 449:507 the metabolic/nutrient sensing protein O-GlcNAc transferase that mediates the O-linked addition of N-acetylglucosamine (GlcNAc) moieties to Ser and Thr residues 449:608 To further interrogate this metabolic influence on axon-glial interactions, we generated OGT-SCKO mice with SC-specific deletion of the metabolic/nutrient sensing protein O-GlcNAc transferase that mediates the O-linked addition of N-acetylglucosamine (GlcNAc) moieties to Ser and Thr residues. 27629714 12 45 theme mutant 1899:1904 arg1 mice 1906:1909 OGT-SCKO and Prx mutant mice 1882:1909 OGT-SCKO and Prx mutant mice 1882:1909 Importantly, phenotypes of OGT-SCKO and Prx mutant mice are very similar, implying that compromised PRX function contributes to the neuropathy of OGT-SCKO mice. 27629714 4 46 theme OGT-SCKO 615:622 arg1 mice 624:627 The OGT-SCKO mice 611:627 The OGT-SCKO mice 611:627 The OGT-SCKO mice develop tomaculous demyelinating neuropathy characterized by focal thickenings of the myelin sheath (tomacula), progressive demyelination, axonal loss, and motor and sensory nerve dysfunction. 27629714 5 47 theme sciatic 897:903 arg1 nerve 905:909 rat sciatic nerve 893:909 rat sciatic nerve 893:909 Proteomic analysis identified more than 100 O-GlcNAcylated proteins in rat sciatic nerve, including Periaxin (PRX), a myelin protein whose mutation causes inherited neuropathy in humans. 27629714 10 48 theme OGT-SCKO 1587:1594 arg1 mice 1596:1599 OGT-SCKO mice 1587:1599 OGT-SCKO mice 1587:1599 SC-specific deletion of OGT (OGT-SCKO mice) causes a tomaculous demyelinating neuropathy accompanied with progressive axon degeneration and motor and sensory nerve dysfunction. 27629714 10 48 theme OGT-SCKO 1587:1594 arg1 OGT 1582:1584 OGT 1582:1584 OGT (OGT-SCKO mice) 1582:1600 SC-specific deletion of OGT (OGT-SCKO mice) causes a tomaculous demyelinating neuropathy accompanied with progressive axon degeneration and motor and sensory nerve dysfunction. 27629714 7 49 theme mice 1157:1160 arg1 phenotypes 1116:1125 phenotypes 1116:1125 phenotypes of OGT-SCKO and Prx-deficient mice 1116:1160 Furthermore, phenotypes of OGT-SCKO and Prx-deficient mice are very similar, suggesting that metabolic control of PRX O-GlcNAcylation is crucial for myelin maintenance and axonal integrity. 27629714 10 50 theme demyelinating 1622:1634 arg1 neuropathy 1636:1645 a tomaculous demyelinating neuropathy 1609:1645 a tomaculous demyelinating neuropathy accompanied with progressive axon degeneration and motor and sensory nerve dysfunction 1609:1732 SC-specific deletion of OGT (OGT-SCKO mice) causes a tomaculous demyelinating neuropathy accompanied with progressive axon degeneration and motor and sensory nerve dysfunction. 27629714 5 51 from neuropathy 987:996 arg1 humans 1001:1006 humans 1001:1006 humans 1001:1006 Proteomic analysis identified more than 100 O-GlcNAcylated proteins in rat sciatic nerve, including Periaxin (PRX), a myelin protein whose mutation causes inherited neuropathy in humans. 27629714 9 52 theme Schwann 1487:1493 arg1 SCs 1502:1504 SCs 1502:1504 SCs 1502:1504 Here we find that OGT functions in Schwann cells (SCs) to maintain normal myelin and prevent axonal loss. 27629714 9 52 theme Schwann 1487:1493 arg1 cells 1495:1499 Schwann cells 1487:1499 Schwann cells (SCs) 1487:1505 Here we find that OGT functions in Schwann cells (SCs) to maintain normal myelin and prevent axonal loss. 27629714 3 53 theme N-acetylglucosamine 548:566 arg1 moieties 577:584 N-acetylglucosamine (GlcNAc) moieties 548:584 N-acetylglucosamine (GlcNAc) moieties 548:584 To further interrogate this metabolic influence on axon-glial interactions, we generated OGT-SCKO mice with SC-specific deletion of the metabolic/nutrient sensing protein O-GlcNAc transferase that mediates the O-linked addition of N-acetylglucosamine (GlcNAc) moieties to Ser and Thr residues. 27629714 1 54 theme peripheral 147:156 arg1 system 166:171 the peripheral nervous system 143:171 the peripheral nervous system 143:171 UNLABELLED Schwann cells (SCs), ensheathing glia of the peripheral nervous system, support axonal survival and function. 27629714 3 55 with mice 415:418 arg1 deletion 437:444 SC-specific deletion 425:444 SC-specific deletion of the metabolic/nutrient sensing protein O-GlcNAc transferase that mediates the O-linked addition of N-acetylglucosamine (GlcNAc) moieties to Ser and Thr residues 425:608 To further interrogate this metabolic influence on axon-glial interactions, we generated OGT-SCKO mice with SC-specific deletion of the metabolic/nutrient sensing protein O-GlcNAc transferase that mediates the O-linked addition of N-acetylglucosamine (GlcNAc) moieties to Ser and Thr residues. 27629714 4 56 theme focal 690:694 arg1 thickenings 696:706 focal thickenings 690:706 focal thickenings of the myelin sheath (tomacula), progressive demyelination, axonal loss, and motor and sensory nerve dysfunction 690:819 The OGT-SCKO mice develop tomaculous demyelinating neuropathy characterized by focal thickenings of the myelin sheath (tomacula), progressive demyelination, axonal loss, and motor and sensory nerve dysfunction. 27629714 10 57 theme progressive 1664:1674 arg1 degeneration 1681:1692 progressive axon degeneration 1664:1692 progressive axon degeneration 1664:1692 SC-specific deletion of OGT (OGT-SCKO mice) causes a tomaculous demyelinating neuropathy accompanied with progressive axon degeneration and motor and sensory nerve dysfunction. 27629714 7 58 theme myelin 1252:1257 arg1 maintenance 1259:1269 myelin maintenance 1252:1269 myelin maintenance 1252:1269 Furthermore, phenotypes of OGT-SCKO and Prx-deficient mice are very similar, suggesting that metabolic control of PRX O-GlcNAcylation is crucial for myelin maintenance and axonal integrity. 27629714 2 59 theme axon 301:304 arg1 integrity 306:314 axon integrity 301:314 axon integrity 301:314 Abnormalities in SC metabolism affect their ability to provide this support and maintain axon integrity. 27629714 1 60 theme system 166:171 arg1 glia 135:138 ensheathing glia 123:138 ensheathing glia of the peripheral nervous system 123:171 UNLABELLED Schwann cells (SCs), ensheathing glia of the peripheral nervous system, support axonal survival and function. 27629714 1 60 theme system 166:171 arg1 cells 110:114 UNLABELLED Schwann cells 91:114 UNLABELLED Schwann cells (SCs) 91:120 UNLABELLED Schwann cells (SCs), ensheathing glia of the peripheral nervous system, support axonal survival and function. 27629714 3 61 theme moieties 577:584 arg1 addition 536:543 the O-linked addition 523:543 the O-linked addition of N-acetylglucosamine (GlcNAc) moieties to Ser and Thr residues 523:608 To further interrogate this metabolic influence on axon-glial interactions, we generated OGT-SCKO mice with SC-specific deletion of the metabolic/nutrient sensing protein O-GlcNAc transferase that mediates the O-linked addition of N-acetylglucosamine (GlcNAc) moieties to Ser and Thr residues. 27629714 3 62 link O-linked 527:534 arg1 addition 536:543 the O-linked addition 523:543 the O-linked addition of N-acetylglucosamine (GlcNAc) moieties to Ser and Thr residues 523:608 To further interrogate this metabolic influence on axon-glial interactions, we generated OGT-SCKO mice with SC-specific deletion of the metabolic/nutrient sensing protein O-GlcNAc transferase that mediates the O-linked addition of N-acetylglucosamine (GlcNAc) moieties to Ser and Thr residues. 27629714 4 63 theme demyelinating 648:660 arg1 neuropathy 662:671 tomaculous demyelinating neuropathy 637:671 tomaculous demyelinating neuropathy characterized by focal thickenings of the myelin sheath (tomacula), progressive demyelination, axonal loss, and motor and sensory nerve dysfunction 637:819 The OGT-SCKO mice develop tomaculous demyelinating neuropathy characterized by focal thickenings of the myelin sheath (tomacula), progressive demyelination, axonal loss, and motor and sensory nerve dysfunction. 27629714 10 64 theme motor 1698:1702 arg1 dysfunction 1722:1732 motor and sensory nerve dysfunction 1698:1732 dysfunction 1722:1732 SC-specific deletion of OGT (OGT-SCKO mice) causes a tomaculous demyelinating neuropathy accompanied with progressive axon degeneration and motor and sensory nerve dysfunction. 27629714 8 65 theme nutrient 1320:1327 arg1 sensing 1329:1335 The nutrient sensing protein O-GlcNAc transferase (OGT) 1316:1370 The nutrient sensing protein O-GlcNAc transferase (OGT) 1316:1370 SIGNIFICANCE STATEMENT The nutrient sensing protein O-GlcNAc transferase (OGT) mediates post-translational O-linked N-acetylglucosamine (GlcNAc) modification. 27629714 3 66 from influence 355:363 arg1 interactions 379:390 axon-glial interactions 368:390 axon-glial interactions 368:390 To further interrogate this metabolic influence on axon-glial interactions, we generated OGT-SCKO mice with SC-specific deletion of the metabolic/nutrient sensing protein O-GlcNAc transferase that mediates the O-linked addition of N-acetylglucosamine (GlcNAc) moieties to Ser and Thr residues. 27629714 12 67 theme OGT-SCKO 2001:2008 arg1 mice 2010:2013 OGT-SCKO mice 2001:2013 OGT-SCKO mice 2001:2013 Importantly, phenotypes of OGT-SCKO and Prx mutant mice are very similar, implying that compromised PRX function contributes to the neuropathy of OGT-SCKO mice. 27629714 8 68 theme protein 1337:1343 arg1 transferase 1354:1364 protein O-GlcNAc transferase 1337:1364 The nutrient sensing protein O-GlcNAc transferase (OGT) 1316:1370 SIGNIFICANCE STATEMENT The nutrient sensing protein O-GlcNAc transferase (OGT) mediates post-translational O-linked N-acetylglucosamine (GlcNAc) modification. 27629714 8 68 theme protein 1337:1343 arg1 OGT 1367:1369 OGT 1367:1369 OGT 1367:1369 SIGNIFICANCE STATEMENT The nutrient sensing protein O-GlcNAc transferase (OGT) mediates post-translational O-linked N-acetylglucosamine (GlcNAc) modification. 27629714 8 69 theme N-acetylglucosamine 1409:1427 arg1 modification 1438:1449 post-translational O-linked N-acetylglucosamine (GlcNAc) modification 1381:1449 post-translational O-linked N-acetylglucosamine (GlcNAc) modification 1381:1449 SIGNIFICANCE STATEMENT The nutrient sensing protein O-GlcNAc transferase (OGT) mediates post-translational O-linked N-acetylglucosamine (GlcNAc) modification. 27629714 4 70 theme progressive 741:751 arg1 demyelination 753:765 progressive demyelination 741:765 progressive demyelination 741:765 The OGT-SCKO mice develop tomaculous demyelinating neuropathy characterized by focal thickenings of the myelin sheath (tomacula), progressive demyelination, axonal loss, and motor and sensory nerve dysfunction. 27629714 11 71 theme inherited 1804:1812 arg1 neuropathy 1814:1823 inherited neuropathy 1804:1823 inherited neuropathy in humans 1804:1833 We also found Periaxin (PRX), a myelin protein whose mutation causes inherited neuropathy in humans, is O-GlcNAcylated. 27629714 1 72 theme ensheathing 123:133 arg1 glia 135:138 ensheathing glia 123:138 ensheathing glia of the peripheral nervous system 123:171 UNLABELLED Schwann cells (SCs), ensheathing glia of the peripheral nervous system, support axonal survival and function. 27629714 1 72 theme ensheathing 123:133 arg1 cells 110:114 UNLABELLED Schwann cells 91:114 UNLABELLED Schwann cells (SCs) 91:120 UNLABELLED Schwann cells (SCs), ensheathing glia of the peripheral nervous system, support axonal survival and function. 27629714 4 73 theme myelin 715:720 arg1 tomacula 730:737 tomacula 730:737 tomacula 730:737 The OGT-SCKO mice develop tomaculous demyelinating neuropathy characterized by focal thickenings of the myelin sheath (tomacula), progressive demyelination, axonal loss, and motor and sensory nerve dysfunction. 27629714 4 73 theme myelin 715:720 arg1 sheath 722:727 the myelin sheath 711:727 the myelin sheath (tomacula) 711:738 The OGT-SCKO mice develop tomaculous demyelinating neuropathy characterized by focal thickenings of the myelin sheath (tomacula), progressive demyelination, axonal loss, and motor and sensory nerve dysfunction. 27629714 3 74 dep Ser 589:591 arg1 residues 601:608 residues 601:608 residues 601:608 To further interrogate this metabolic influence on axon-glial interactions, we generated OGT-SCKO mice with SC-specific deletion of the metabolic/nutrient sensing protein O-GlcNAc transferase that mediates the O-linked addition of N-acetylglucosamine (GlcNAc) moieties to Ser and Thr residues. 27629714 5 75 theme inherited 977:985 arg1 neuropathy 987:996 inherited neuropathy 977:996 inherited neuropathy in humans 977:1006 Proteomic analysis identified more than 100 O-GlcNAcylated proteins in rat sciatic nerve, including Periaxin (PRX), a myelin protein whose mutation causes inherited neuropathy in humans. 27629714 8 76 theme O-linked 1400:1407 arg1 GlcNAc 1430:1435 GlcNAc 1430:1435 GlcNAc 1430:1435 SIGNIFICANCE STATEMENT The nutrient sensing protein O-GlcNAc transferase (OGT) mediates post-translational O-linked N-acetylglucosamine (GlcNAc) modification. 27629714 8 76 theme O-linked 1400:1407 arg1 N-acetylglucosamine 1409:1427 O-linked N-acetylglucosamine 1400:1427 post-translational O-linked N-acetylglucosamine (GlcNAc) modification 1381:1449 SIGNIFICANCE STATEMENT The nutrient sensing protein O-GlcNAc transferase (OGT) mediates post-translational O-linked N-acetylglucosamine (GlcNAc) modification. 27629714 7 77 theme PRX 1217:1219 arg1 O-GlcNAcylation 1221:1235 PRX O-GlcNAcylation 1217:1235 PRX O-GlcNAcylation 1217:1235 Furthermore, phenotypes of OGT-SCKO and Prx-deficient mice are very similar, suggesting that metabolic control of PRX O-GlcNAcylation is crucial for myelin maintenance and axonal integrity. 27629714 13 78 theme PNS 2092:2094 arg1 function 2096:2103 PNS function 2092:2103 PNS function and in developing new strategies for treating peripheral neuropathy by targeting SC function 2092:2196 This study will be useful in understanding how SC metabolism contributes to PNS function and in developing new strategies for treating peripheral neuropathy by targeting SC function. 27629714 1 79 theme axonal 182:187 arg1 survival 189:196 axonal survival 182:196 axonal survival 182:196 UNLABELLED Schwann cells (SCs), ensheathing glia of the peripheral nervous system, support axonal survival and function. 27629714 10 80 theme nerve 1716:1720 arg1 dysfunction 1722:1732 motor and sensory nerve dysfunction 1698:1732 dysfunction 1722:1732 SC-specific deletion of OGT (OGT-SCKO mice) causes a tomaculous demyelinating neuropathy accompanied with progressive axon degeneration and motor and sensory nerve dysfunction. 27629714 0 81 theme Cell 8:11 arg1 Glycosylation 22:34 Schwann Cell O-GlcNAc Glycosylation 0:34 Schwann Cell O-GlcNAc Glycosylation 0:34 Schwann Cell O-GlcNAc Glycosylation Is Required for Myelin Maintenance and Axon Integrity. 27629714 12 82 theme PRX 1955:1957 arg1 function 1959:1966 compromised PRX function 1943:1966 compromised PRX function 1943:1966 Importantly, phenotypes of OGT-SCKO and Prx mutant mice are very similar, implying that compromised PRX function contributes to the neuropathy of OGT-SCKO mice. 27629714 2 83 from Abnormalities 212:224 arg1 metabolism 232:241 SC metabolism 229:241 SC metabolism 229:241 Abnormalities in SC metabolism affect their ability to provide this support and maintain axon integrity. 27629714 6 84 theme animals 1094:1100 arg1 sheath 1071:1076 the myelin sheath 1060:1076 the myelin sheath of these mutant animals 1060:1100 PRX lacking O-GlcNAcylation is mislocalized within the myelin sheath of these mutant animals. 27629714 3 85 theme SC-specific 425:435 arg1 deletion 437:444 SC-specific deletion 425:444 SC-specific deletion of the metabolic/nutrient sensing protein O-GlcNAc transferase that mediates the O-linked addition of N-acetylglucosamine (GlcNAc) moieties to Ser and Thr residues 425:608 To further interrogate this metabolic influence on axon-glial interactions, we generated OGT-SCKO mice with SC-specific deletion of the metabolic/nutrient sensing protein O-GlcNAc transferase that mediates the O-linked addition of N-acetylglucosamine (GlcNAc) moieties to Ser and Thr residues. 27629714 1 86 theme Schwann 102:108 arg1 glia 135:138 ensheathing glia 123:138 ensheathing glia of the peripheral nervous system 123:171 UNLABELLED Schwann cells (SCs), ensheathing glia of the peripheral nervous system, support axonal survival and function. 27629714 1 86 theme Schwann 102:108 arg1 SCs 117:119 SCs 117:119 SCs 117:119 UNLABELLED Schwann cells (SCs), ensheathing glia of the peripheral nervous system, support axonal survival and function. 27629714 1 86 theme Schwann 102:108 arg1 cells 110:114 UNLABELLED Schwann cells 91:114 UNLABELLED Schwann cells (SCs) 91:120 UNLABELLED Schwann cells (SCs), ensheathing glia of the peripheral nervous system, support axonal survival and function. 27629714 3 87 theme axon-glial 368:377 arg1 interactions 379:390 axon-glial interactions 368:390 axon-glial interactions 368:390 To further interrogate this metabolic influence on axon-glial interactions, we generated OGT-SCKO mice with SC-specific deletion of the metabolic/nutrient sensing protein O-GlcNAc transferase that mediates the O-linked addition of N-acetylglucosamine (GlcNAc) moieties to Ser and Thr residues. 27629714 4 88 theme loss 775:778 arg1 thickenings 696:706 focal thickenings 690:706 focal thickenings of the myelin sheath (tomacula), progressive demyelination, axonal loss, and motor and sensory nerve dysfunction 690:819 The OGT-SCKO mice develop tomaculous demyelinating neuropathy characterized by focal thickenings of the myelin sheath (tomacula), progressive demyelination, axonal loss, and motor and sensory nerve dysfunction. 27629714 3 89 theme protein 480:486 arg1 transferase 497:507 the metabolic/nutrient sensing protein O-GlcNAc transferase 449:507 the metabolic/nutrient sensing protein O-GlcNAc transferase that mediates the O-linked addition of N-acetylglucosamine (GlcNAc) moieties to Ser and Thr residues 449:608 To further interrogate this metabolic influence on axon-glial interactions, we generated OGT-SCKO mice with SC-specific deletion of the metabolic/nutrient sensing protein O-GlcNAc transferase that mediates the O-linked addition of N-acetylglucosamine (GlcNAc) moieties to Ser and Thr residues. 27629714 3 90 theme metabolic/nutrient 453:470 arg1 transferase 497:507 the metabolic/nutrient sensing protein O-GlcNAc transferase 449:507 the metabolic/nutrient sensing protein O-GlcNAc transferase that mediates the O-linked addition of N-acetylglucosamine (GlcNAc) moieties to Ser and Thr residues 449:608 To further interrogate this metabolic influence on axon-glial interactions, we generated OGT-SCKO mice with SC-specific deletion of the metabolic/nutrient sensing protein O-GlcNAc transferase that mediates the O-linked addition of N-acetylglucosamine (GlcNAc) moieties to Ser and Thr residues. 27629714 0 91 theme Myelin 52:57 arg1 Maintenance 59:69 Myelin Maintenance 52:69 Myelin Maintenance 52:69 Schwann Cell O-GlcNAc Glycosylation Is Required for Myelin Maintenance and Axon Integrity. 27629714 12 92 theme Prx 1895:1897 arg1 mice 1906:1909 OGT-SCKO and Prx mutant mice 1882:1909 OGT-SCKO and Prx mutant mice 1882:1909 Importantly, phenotypes of OGT-SCKO and Prx mutant mice are very similar, implying that compromised PRX function contributes to the neuropathy of OGT-SCKO mice. 27629714 11 93 theme myelin 1767:1772 arg1 Periaxin 1749:1756 Periaxin 1749:1756 Periaxin (PRX) 1749:1762 We also found Periaxin (PRX), a myelin protein whose mutation causes inherited neuropathy in humans, is O-GlcNAcylated. 27629714 11 93 theme myelin 1767:1772 arg1 protein 1774:1780 a myelin protein 1765:1780 a myelin protein whose mutation causes inherited neuropathy in humans 1765:1833 We also found Periaxin (PRX), a myelin protein whose mutation causes inherited neuropathy in humans, is O-GlcNAcylated. 27629714 12 94 theme mice 1906:1909 arg1 phenotypes 1868:1877 phenotypes 1868:1877 phenotypes of OGT-SCKO and Prx mutant mice 1868:1909 Importantly, phenotypes of OGT-SCKO and Prx mutant mice are very similar, implying that compromised PRX function contributes to the neuropathy of OGT-SCKO mice. 27629714 10 95 theme SC-specific 1558:1568 arg1 deletion 1570:1577 SC-specific deletion 1558:1577 SC-specific deletion of OGT (OGT-SCKO mice) 1558:1600 SC-specific deletion of OGT (OGT-SCKO mice) causes a tomaculous demyelinating neuropathy accompanied with progressive axon degeneration and motor and sensory nerve dysfunction. 27629714 4 96 theme nerve 803:807 arg1 dysfunction 809:819 motor and sensory nerve dysfunction 785:819 dysfunction 809:819 The OGT-SCKO mice develop tomaculous demyelinating neuropathy characterized by focal thickenings of the myelin sheath (tomacula), progressive demyelination, axonal loss, and motor and sensory nerve dysfunction. 27629714 8 97 dep sensing 1329:1335 arg1 transferase 1354:1364 protein O-GlcNAc transferase 1337:1364 The nutrient sensing protein O-GlcNAc transferase (OGT) 1316:1370 SIGNIFICANCE STATEMENT The nutrient sensing protein O-GlcNAc transferase (OGT) mediates post-translational O-linked N-acetylglucosamine (GlcNAc) modification. 27629714 8 97 dep sensing 1329:1335 arg1 OGT 1367:1369 OGT 1367:1369 OGT 1367:1369 SIGNIFICANCE STATEMENT The nutrient sensing protein O-GlcNAc transferase (OGT) mediates post-translational O-linked N-acetylglucosamine (GlcNAc) modification. 27629714 3 98 theme transferase 497:507 arg1 deletion 437:444 SC-specific deletion 425:444 SC-specific deletion of the metabolic/nutrient sensing protein O-GlcNAc transferase that mediates the O-linked addition of N-acetylglucosamine (GlcNAc) moieties to Ser and Thr residues 425:608 To further interrogate this metabolic influence on axon-glial interactions, we generated OGT-SCKO mice with SC-specific deletion of the metabolic/nutrient sensing protein O-GlcNAc transferase that mediates the O-linked addition of N-acetylglucosamine (GlcNAc) moieties to Ser and Thr residues. 27629714 4 99 theme tomaculous 637:646 arg1 neuropathy 662:671 tomaculous demyelinating neuropathy 637:671 tomaculous demyelinating neuropathy characterized by focal thickenings of the myelin sheath (tomacula), progressive demyelination, axonal loss, and motor and sensory nerve dysfunction 637:819 The OGT-SCKO mice develop tomaculous demyelinating neuropathy characterized by focal thickenings of the myelin sheath (tomacula), progressive demyelination, axonal loss, and motor and sensory nerve dysfunction. 27816939 0 0 theme DNA 87:89 arg1 Repair 98:103 Oxidative Mitochondrial DNA Lesion Repair 63:103 Oxidative Mitochondrial DNA Lesion Repair in Diabetic Hearts 63:122 O-GlcNAcylation of 8-Oxoguanine DNA Glycosylase (Ogg1) Impairs Oxidative Mitochondrial DNA Lesion Repair in Diabetic Hearts. 27816939 7 1 dep In 1024:1025 arg1 vitro 1027:1031 vitro 1027:1031 vitro 1027:1031 In vitro experiments demonstrated that O-GlcNAcylation inhibits Ogg1 activity, which could explain the mtDNA lesion accumulation observed in vivo Reducing Ogg1 O-GlcNAcylation in vivo by introducing a dominant negative O-GlcNAc transferase mutant (F460A) restored Ogg1 enzymatic activity and, consequently, reduced 8-OHdG and mtDNA damage despite the adverse hyperglycemic milieu. 27816939 2 2 theme 8-hydroxy-2'-deoxyguanosine 350:376 arg1 lesion 295:300 A prevalent lesion 283:300 A prevalent lesion that occurs in mtDNA damage 283:328 A prevalent lesion that occurs in mtDNA damage is the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG), which can cause mutations when not repaired properly by 8-oxoguanine DNA glycosylase (Ogg1). 27816939 2 2 theme 8-hydroxy-2'-deoxyguanosine 350:376 arg1 formation 337:345 the formation 333:345 the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG), which can cause mutations when not repaired properly by 8-oxoguanine DNA glycosylase (Ogg1) 333:478 A prevalent lesion that occurs in mtDNA damage is the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG), which can cause mutations when not repaired properly by 8-oxoguanine DNA glycosylase (Ogg1). 27816939 0 3 theme Mitochondrial 73:85 arg1 Repair 98:103 Oxidative Mitochondrial DNA Lesion Repair 63:103 Oxidative Mitochondrial DNA Lesion Repair in Diabetic Hearts 63:122 O-GlcNAcylation of 8-Oxoguanine DNA Glycosylase (Ogg1) Impairs Oxidative Mitochondrial DNA Lesion Repair in Diabetic Hearts. 27816939 7 4 theme Ogg1 1088:1091 arg1 activity 1093:1100 Ogg1 activity 1088:1100 Ogg1 activity 1088:1100 In vitro experiments demonstrated that O-GlcNAcylation inhibits Ogg1 activity, which could explain the mtDNA lesion accumulation observed in vivo Reducing Ogg1 O-GlcNAcylation in vivo by introducing a dominant negative O-GlcNAc transferase mutant (F460A) restored Ogg1 enzymatic activity and, consequently, reduced 8-OHdG and mtDNA damage despite the adverse hyperglycemic milieu. 27816939 5 5 theme increased 857:865 arg1 levels 867:872 increased levels 857:872 increased levels of 8-OHdG 857:882 In diabetic hearts, we further observed increased levels of 8-OHdG and an increased amount of mtDNA damage. 27816939 3 6 theme repair 500:505 arg1 machinery 507:515 the mtDNA repair machinery 490:515 the mtDNA repair machinery 490:515 Although the mtDNA repair machinery has been described in cardiac myocytes, the regulation of this repair has been incompletely investigated. 27816939 5 7 theme increased 891:899 arg1 8-OHdG 877:882 8-OHdG 877:882 8-OHdG 877:882 In diabetic hearts, we further observed increased levels of 8-OHdG and an increased amount of mtDNA damage. 27816939 5 7 theme increased 891:899 arg1 amount 901:906 an increased amount 888:906 an increased amount of mtDNA damage 888:922 In diabetic hearts, we further observed increased levels of 8-OHdG and an increased amount of mtDNA damage. 27816939 5 7 theme increased 891:899 arg1 damage 917:922 mtDNA damage 911:922 mtDNA damage 911:922 In diabetic hearts, we further observed increased levels of 8-OHdG and an increased amount of mtDNA damage. 27816939 7 8 theme Reducing 1170:1177 arg1 O-GlcNAcylation 1184:1198 vivo Reducing Ogg1 O-GlcNAcylation 1165:1198 vivo Reducing Ogg1 O-GlcNAcylation 1165:1198 In vitro experiments demonstrated that O-GlcNAcylation inhibits Ogg1 activity, which could explain the mtDNA lesion accumulation observed in vivo Reducing Ogg1 O-GlcNAcylation in vivo by introducing a dominant negative O-GlcNAc transferase mutant (F460A) restored Ogg1 enzymatic activity and, consequently, reduced 8-OHdG and mtDNA damage despite the adverse hyperglycemic milieu. 27816939 4 9 theme lower 743:747 arg1 activity 754:761 significantly lower Ogg1 activity 729:761 significantly lower Ogg1 activity 729:761 Here we report that the hearts of type 1 diabetic mice, despite having increased Ogg1 protein levels, had significantly lower Ogg1 activity than the hearts of control, non-type 1 diabetic mice. 27816939 4 10 dep mice 811:814 arg1 non-type 791:798 control, non-type 1 diabetic mice 782:814 non-type 791:798 Here we report that the hearts of type 1 diabetic mice, despite having increased Ogg1 protein levels, had significantly lower Ogg1 activity than the hearts of control, non-type 1 diabetic mice. 27816939 1 11 theme diabetic 258:265 arg1 cardiomyopathy 267:280 diabetic cardiomyopathy 258:280 diabetic cardiomyopathy 258:280 mtDNA damage in cardiac myocytes resulting from increased oxidative stress is emerging as an important factor in the pathogenesis of diabetic cardiomyopathy. 27816939 0 12 theme Lesion 91:96 arg1 Repair 98:103 Oxidative Mitochondrial DNA Lesion Repair 63:103 Oxidative Mitochondrial DNA Lesion Repair in Diabetic Hearts 63:122 O-GlcNAcylation of 8-Oxoguanine DNA Glycosylase (Ogg1) Impairs Oxidative Mitochondrial DNA Lesion Repair in Diabetic Hearts. 27816939 3 13 theme cardiac 539:545 arg1 myocytes 547:554 cardiac myocytes 539:554 cardiac myocytes 539:554 Although the mtDNA repair machinery has been described in cardiac myocytes, the regulation of this repair has been incompletely investigated. 27816939 2 14 theme prevalent 285:293 arg1 lesion 295:300 A prevalent lesion 283:300 A prevalent lesion that occurs in mtDNA damage 283:328 A prevalent lesion that occurs in mtDNA damage is the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG), which can cause mutations when not repaired properly by 8-oxoguanine DNA glycosylase (Ogg1). 27816939 2 14 theme prevalent 285:293 arg1 formation 337:345 the formation 333:345 the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG), which can cause mutations when not repaired properly by 8-oxoguanine DNA glycosylase (Ogg1) 333:478 A prevalent lesion that occurs in mtDNA damage is the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG), which can cause mutations when not repaired properly by 8-oxoguanine DNA glycosylase (Ogg1). 27816939 8 15 theme diabetic 1581:1588 arg1 cardiomyopathy 1590:1603 diabetic cardiomyopathy 1581:1603 diabetic cardiomyopathy 1581:1603 Taken together, our results implicate hyperglycemia-induced O-GlcNAcylation of Ogg1 in increased mtDNA damage and, therefore, provide a new plausible biochemical mechanism for diabetic cardiomyopathy. 27816939 1 16 theme cardiomyopathy 267:280 arg1 pathogenesis 242:253 the pathogenesis 238:253 the pathogenesis of diabetic cardiomyopathy 238:280 mtDNA damage in cardiac myocytes resulting from increased oxidative stress is emerging as an important factor in the pathogenesis of diabetic cardiomyopathy. 27816939 0 17 theme Diabetic 108:115 arg1 Hearts 117:122 Diabetic Hearts 108:122 Diabetic Hearts 108:122 O-GlcNAcylation of 8-Oxoguanine DNA Glycosylase (Ogg1) Impairs Oxidative Mitochondrial DNA Lesion Repair in Diabetic Hearts. 27816939 4 18 theme mice 811:814 arg1 hearts 772:777 the hearts 768:777 the hearts of control, non-type 1 diabetic mice 768:814 Here we report that the hearts of type 1 diabetic mice, despite having increased Ogg1 protein levels, had significantly lower Ogg1 activity than the hearts of control, non-type 1 diabetic mice. 27816939 7 19 theme enzymatic 1293:1301 arg1 activity 1303:1310 Ogg1 enzymatic activity 1288:1310 Ogg1 enzymatic activity 1288:1310 In vitro experiments demonstrated that O-GlcNAcylation inhibits Ogg1 activity, which could explain the mtDNA lesion accumulation observed in vivo Reducing Ogg1 O-GlcNAcylation in vivo by introducing a dominant negative O-GlcNAc transferase mutant (F460A) restored Ogg1 enzymatic activity and, consequently, reduced 8-OHdG and mtDNA damage despite the adverse hyperglycemic milieu. 27816939 5 20 theme diabetic 820:827 arg1 hearts 829:834 diabetic hearts 820:834 diabetic hearts 820:834 In diabetic hearts, we further observed increased levels of 8-OHdG and an increased amount of mtDNA damage. 27816939 7 21 theme vivo 1165:1168 arg1 O-GlcNAcylation 1184:1198 vivo Reducing Ogg1 O-GlcNAcylation 1165:1198 vivo Reducing Ogg1 O-GlcNAcylation 1165:1198 In vitro experiments demonstrated that O-GlcNAcylation inhibits Ogg1 activity, which could explain the mtDNA lesion accumulation observed in vivo Reducing Ogg1 O-GlcNAcylation in vivo by introducing a dominant negative O-GlcNAc transferase mutant (F460A) restored Ogg1 enzymatic activity and, consequently, reduced 8-OHdG and mtDNA damage despite the adverse hyperglycemic milieu. 27816939 4 22 theme diabetic 802:809 arg1 mice 811:814 control, non-type 1 diabetic mice 782:814 mice 811:814 Here we report that the hearts of type 1 diabetic mice, despite having increased Ogg1 protein levels, had significantly lower Ogg1 activity than the hearts of control, non-type 1 diabetic mice. 27816939 6 23 from mice 995:998 arg1 O-GlcNAcylated 968:981 O-GlcNAcylated 968:981 O-GlcNAcylated 968:981 Interestingly, Ogg1 was found to be highly O-GlcNAcylated in diabetic mice compared with controls. 27816939 4 24 theme Ogg1 749:752 arg1 activity 754:761 significantly lower Ogg1 activity 729:761 significantly lower Ogg1 activity 729:761 Here we report that the hearts of type 1 diabetic mice, despite having increased Ogg1 protein levels, had significantly lower Ogg1 activity than the hearts of control, non-type 1 diabetic mice. 27816939 1 25 theme increased 173:181 arg1 stress 193:198 increased oxidative stress 173:198 increased oxidative stress 173:198 mtDNA damage in cardiac myocytes resulting from increased oxidative stress is emerging as an important factor in the pathogenesis of diabetic cardiomyopathy. 27816939 2 26 theme 8-oxoguanine 444:455 arg1 glycosylase 461:471 8-oxoguanine DNA glycosylase 444:471 8-oxoguanine DNA glycosylase (Ogg1) 444:478 A prevalent lesion that occurs in mtDNA damage is the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG), which can cause mutations when not repaired properly by 8-oxoguanine DNA glycosylase (Ogg1). 27816939 2 26 theme 8-oxoguanine 444:455 arg1 Ogg1 474:477 Ogg1 474:477 Ogg1 474:477 A prevalent lesion that occurs in mtDNA damage is the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG), which can cause mutations when not repaired properly by 8-oxoguanine DNA glycosylase (Ogg1). 27816939 1 27 from damage 131:136 arg1 myocytes 149:156 cardiac myocytes 141:156 cardiac myocytes resulting from increased oxidative stress 141:198 mtDNA damage in cardiac myocytes resulting from increased oxidative stress is emerging as an important factor in the pathogenesis of diabetic cardiomyopathy. 27816939 2 28 theme mtDNA 317:321 arg1 damage 323:328 mtDNA damage 317:328 mtDNA damage 317:328 A prevalent lesion that occurs in mtDNA damage is the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG), which can cause mutations when not repaired properly by 8-oxoguanine DNA glycosylase (Ogg1). 27816939 7 29 theme transferase 1252:1262 arg1 F460A 1272:1276 F460A 1272:1276 F460A 1272:1276 In vitro experiments demonstrated that O-GlcNAcylation inhibits Ogg1 activity, which could explain the mtDNA lesion accumulation observed in vivo Reducing Ogg1 O-GlcNAcylation in vivo by introducing a dominant negative O-GlcNAc transferase mutant (F460A) restored Ogg1 enzymatic activity and, consequently, reduced 8-OHdG and mtDNA damage despite the adverse hyperglycemic milieu. 27816939 7 29 theme transferase 1252:1262 arg1 mutant 1264:1269 a dominant negative O-GlcNAc transferase mutant 1223:1269 a dominant negative O-GlcNAc transferase mutant (F460A) 1223:1277 In vitro experiments demonstrated that O-GlcNAcylation inhibits Ogg1 activity, which could explain the mtDNA lesion accumulation observed in vivo Reducing Ogg1 O-GlcNAcylation in vivo by introducing a dominant negative O-GlcNAc transferase mutant (F460A) restored Ogg1 enzymatic activity and, consequently, reduced 8-OHdG and mtDNA damage despite the adverse hyperglycemic milieu. 27816939 1 30 theme oxidative 183:191 arg1 stress 193:198 increased oxidative stress 173:198 increased oxidative stress 173:198 mtDNA damage in cardiac myocytes resulting from increased oxidative stress is emerging as an important factor in the pathogenesis of diabetic cardiomyopathy. 27816939 8 31 theme new 1541:1543 arg1 mechanism 1567:1575 a new plausible biochemical mechanism 1539:1575 a new plausible biochemical mechanism for diabetic cardiomyopathy 1539:1603 Taken together, our results implicate hyperglycemia-induced O-GlcNAcylation of Ogg1 in increased mtDNA damage and, therefore, provide a new plausible biochemical mechanism for diabetic cardiomyopathy. 27816939 4 32 theme protein 709:715 arg1 levels 717:722 increased Ogg1 protein levels 694:722 increased Ogg1 protein levels 694:722 Here we report that the hearts of type 1 diabetic mice, despite having increased Ogg1 protein levels, had significantly lower Ogg1 activity than the hearts of control, non-type 1 diabetic mice. 27816939 0 33 theme DNA 32:34 arg1 Ogg1 49:52 Ogg1 49:52 Ogg1 49:52 O-GlcNAcylation of 8-Oxoguanine DNA Glycosylase (Ogg1) Impairs Oxidative Mitochondrial DNA Lesion Repair in Diabetic Hearts. 27816939 0 33 theme DNA 32:34 arg1 Glycosylase 36:46 8-Oxoguanine DNA Glycosylase 19:46 8-Oxoguanine DNA Glycosylase (Ogg1) 19:53 O-GlcNAcylation of 8-Oxoguanine DNA Glycosylase (Ogg1) Impairs Oxidative Mitochondrial DNA Lesion Repair in Diabetic Hearts. 27816939 4 34 contain had 725:727 arg2 activity 754:761 significantly lower Ogg1 activity 729:761 significantly lower Ogg1 activity 729:761 Here we report that the hearts of type 1 diabetic mice, despite having increased Ogg1 protein levels, had significantly lower Ogg1 activity than the hearts of control, non-type 1 diabetic mice. 27816939 4 34 contain had 725:727 arg1 hearts 647:652 the hearts 643:652 the hearts of type 1 diabetic mice 643:676 Here we report that the hearts of type 1 diabetic mice, despite having increased Ogg1 protein levels, had significantly lower Ogg1 activity than the hearts of control, non-type 1 diabetic mice. 27816939 7 35 theme In 1024:1025 arg1 experiments 1033:1043 In vitro experiments 1024:1043 In vitro experiments 1024:1043 In vitro experiments demonstrated that O-GlcNAcylation inhibits Ogg1 activity, which could explain the mtDNA lesion accumulation observed in vivo Reducing Ogg1 O-GlcNAcylation in vivo by introducing a dominant negative O-GlcNAc transferase mutant (F460A) restored Ogg1 enzymatic activity and, consequently, reduced 8-OHdG and mtDNA damage despite the adverse hyperglycemic milieu. 27816939 5 36 theme mtDNA 911:915 arg1 damage 917:922 mtDNA damage 911:922 mtDNA damage 911:922 In diabetic hearts, we further observed increased levels of 8-OHdG and an increased amount of mtDNA damage. 27816939 0 37 theme 8-Oxoguanine 19:30 arg1 Ogg1 49:52 Ogg1 49:52 Ogg1 49:52 O-GlcNAcylation of 8-Oxoguanine DNA Glycosylase (Ogg1) Impairs Oxidative Mitochondrial DNA Lesion Repair in Diabetic Hearts. 27816939 0 37 theme 8-Oxoguanine 19:30 arg1 Glycosylase 36:46 8-Oxoguanine DNA Glycosylase 19:46 8-Oxoguanine DNA Glycosylase (Ogg1) 19:53 O-GlcNAcylation of 8-Oxoguanine DNA Glycosylase (Ogg1) Impairs Oxidative Mitochondrial DNA Lesion Repair in Diabetic Hearts. 27816939 8 38 theme biochemical 1555:1565 arg1 mechanism 1567:1575 a new plausible biochemical mechanism 1539:1575 a new plausible biochemical mechanism for diabetic cardiomyopathy 1539:1603 Taken together, our results implicate hyperglycemia-induced O-GlcNAcylation of Ogg1 in increased mtDNA damage and, therefore, provide a new plausible biochemical mechanism for diabetic cardiomyopathy. 27816939 4 39 theme mice 673:676 arg1 hearts 647:652 the hearts 643:652 the hearts of type 1 diabetic mice 643:676 Here we report that the hearts of type 1 diabetic mice, despite having increased Ogg1 protein levels, had significantly lower Ogg1 activity than the hearts of control, non-type 1 diabetic mice. 27816939 7 40 theme hyperglycemic 1383:1395 arg1 milieu 1397:1402 the adverse hyperglycemic milieu 1371:1402 the adverse hyperglycemic milieu 1371:1402 In vitro experiments demonstrated that O-GlcNAcylation inhibits Ogg1 activity, which could explain the mtDNA lesion accumulation observed in vivo Reducing Ogg1 O-GlcNAcylation in vivo by introducing a dominant negative O-GlcNAc transferase mutant (F460A) restored Ogg1 enzymatic activity and, consequently, reduced 8-OHdG and mtDNA damage despite the adverse hyperglycemic milieu. 27816939 7 41 theme Ogg1 1288:1291 arg1 activity 1303:1310 Ogg1 enzymatic activity 1288:1310 Ogg1 enzymatic activity 1288:1310 In vitro experiments demonstrated that O-GlcNAcylation inhibits Ogg1 activity, which could explain the mtDNA lesion accumulation observed in vivo Reducing Ogg1 O-GlcNAcylation in vivo by introducing a dominant negative O-GlcNAc transferase mutant (F460A) restored Ogg1 enzymatic activity and, consequently, reduced 8-OHdG and mtDNA damage despite the adverse hyperglycemic milieu. 27816939 3 42 theme mtDNA 494:498 arg1 machinery 507:515 the mtDNA repair machinery 490:515 the mtDNA repair machinery 490:515 Although the mtDNA repair machinery has been described in cardiac myocytes, the regulation of this repair has been incompletely investigated. 27816939 8 43 theme plausible 1545:1553 arg1 mechanism 1567:1575 a new plausible biochemical mechanism 1539:1575 a new plausible biochemical mechanism for diabetic cardiomyopathy 1539:1603 Taken together, our results implicate hyperglycemia-induced O-GlcNAcylation of Ogg1 in increased mtDNA damage and, therefore, provide a new plausible biochemical mechanism for diabetic cardiomyopathy. 27816939 7 44 dep restored 1279:1286 arg1 reduced 1331:1337 reduced 1331:1337 reduced 8-OHdG and mtDNA damage despite the adverse hyperglycemic milieu 1331:1402 In vitro experiments demonstrated that O-GlcNAcylation inhibits Ogg1 activity, which could explain the mtDNA lesion accumulation observed in vivo Reducing Ogg1 O-GlcNAcylation in vivo by introducing a dominant negative O-GlcNAc transferase mutant (F460A) restored Ogg1 enzymatic activity and, consequently, reduced 8-OHdG and mtDNA damage despite the adverse hyperglycemic milieu. 27816939 7 45 theme dominant 1225:1232 arg1 F460A 1272:1276 F460A 1272:1276 F460A 1272:1276 In vitro experiments demonstrated that O-GlcNAcylation inhibits Ogg1 activity, which could explain the mtDNA lesion accumulation observed in vivo Reducing Ogg1 O-GlcNAcylation in vivo by introducing a dominant negative O-GlcNAc transferase mutant (F460A) restored Ogg1 enzymatic activity and, consequently, reduced 8-OHdG and mtDNA damage despite the adverse hyperglycemic milieu. 27816939 7 45 theme dominant 1225:1232 arg1 mutant 1264:1269 a dominant negative O-GlcNAc transferase mutant 1223:1269 a dominant negative O-GlcNAc transferase mutant (F460A) 1223:1277 In vitro experiments demonstrated that O-GlcNAcylation inhibits Ogg1 activity, which could explain the mtDNA lesion accumulation observed in vivo Reducing Ogg1 O-GlcNAcylation in vivo by introducing a dominant negative O-GlcNAc transferase mutant (F460A) restored Ogg1 enzymatic activity and, consequently, reduced 8-OHdG and mtDNA damage despite the adverse hyperglycemic milieu. 27816939 3 46 theme repair 580:585 arg1 regulation 561:570 the regulation 557:570 the regulation of this repair 557:585 Although the mtDNA repair machinery has been described in cardiac myocytes, the regulation of this repair has been incompletely investigated. 27816939 0 47 theme Glycosylase 36:46 arg1 O-GlcNAcylation 0:14 O-GlcNAcylation 0:14 O-GlcNAcylation of 8-Oxoguanine DNA Glycosylase (Ogg1) 0:53 O-GlcNAcylation of 8-Oxoguanine DNA Glycosylase (Ogg1) Impairs Oxidative Mitochondrial DNA Lesion Repair in Diabetic Hearts. 27816939 8 48 theme hyperglycemia-induced 1443:1463 arg1 O-GlcNAcylation 1465:1479 hyperglycemia-induced O-GlcNAcylation 1443:1479 hyperglycemia-induced O-GlcNAcylation of Ogg1 1443:1487 Taken together, our results implicate hyperglycemia-induced O-GlcNAcylation of Ogg1 in increased mtDNA damage and, therefore, provide a new plausible biochemical mechanism for diabetic cardiomyopathy. 27816939 4 49 theme control 782:788 arg1 mice 811:814 control, non-type 1 diabetic mice 782:814 mice 811:814 Here we report that the hearts of type 1 diabetic mice, despite having increased Ogg1 protein levels, had significantly lower Ogg1 activity than the hearts of control, non-type 1 diabetic mice. 27816939 6 50 theme diabetic 986:993 arg1 mice 995:998 diabetic mice 986:998 diabetic mice 986:998 Interestingly, Ogg1 was found to be highly O-GlcNAcylated in diabetic mice compared with controls. 27816939 8 51 dep implicate 1433:1441 arg1 provide 1531:1537 provide 1531:1537 provide a new plausible biochemical mechanism for diabetic cardiomyopathy 1531:1603 Taken together, our results implicate hyperglycemia-induced O-GlcNAcylation of Ogg1 in increased mtDNA damage and, therefore, provide a new plausible biochemical mechanism for diabetic cardiomyopathy. 27816939 8 52 theme increased 1492:1500 arg1 damage 1508:1513 increased mtDNA damage 1492:1513 increased mtDNA damage 1492:1513 Taken together, our results implicate hyperglycemia-induced O-GlcNAcylation of Ogg1 in increased mtDNA damage and, therefore, provide a new plausible biochemical mechanism for diabetic cardiomyopathy. 27816939 2 53 theme DNA 457:459 arg1 glycosylase 461:471 8-oxoguanine DNA glycosylase 444:471 8-oxoguanine DNA glycosylase (Ogg1) 444:478 A prevalent lesion that occurs in mtDNA damage is the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG), which can cause mutations when not repaired properly by 8-oxoguanine DNA glycosylase (Ogg1). 27816939 2 53 theme DNA 457:459 arg1 Ogg1 474:477 Ogg1 474:477 Ogg1 474:477 A prevalent lesion that occurs in mtDNA damage is the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG), which can cause mutations when not repaired properly by 8-oxoguanine DNA glycosylase (Ogg1). 27816939 7 54 theme mtDNA 1350:1354 arg1 damage 1356:1361 mtDNA damage 1350:1361 mtDNA damage 1350:1361 In vitro experiments demonstrated that O-GlcNAcylation inhibits Ogg1 activity, which could explain the mtDNA lesion accumulation observed in vivo Reducing Ogg1 O-GlcNAcylation in vivo by introducing a dominant negative O-GlcNAc transferase mutant (F460A) restored Ogg1 enzymatic activity and, consequently, reduced 8-OHdG and mtDNA damage despite the adverse hyperglycemic milieu. 27816939 5 55 theme 8-OHdG 877:882 arg1 8-OHdG 877:882 8-OHdG 877:882 8-OHdG 877:882 In diabetic hearts, we further observed increased levels of 8-OHdG and an increased amount of mtDNA damage. 27816939 5 55 theme 8-OHdG 877:882 arg1 levels 867:872 increased levels 857:872 increased levels of 8-OHdG 857:882 In diabetic hearts, we further observed increased levels of 8-OHdG and an increased amount of mtDNA damage. 27816939 5 55 theme 8-OHdG 877:882 arg1 amount 901:906 an increased amount 888:906 an increased amount of mtDNA damage 888:922 In diabetic hearts, we further observed increased levels of 8-OHdG and an increased amount of mtDNA damage. 27816939 5 55 theme 8-OHdG 877:882 arg1 damage 917:922 mtDNA damage 911:922 mtDNA damage 911:922 In diabetic hearts, we further observed increased levels of 8-OHdG and an increased amount of mtDNA damage. 27816939 7 56 theme mtDNA 1127:1131 arg1 accumulation 1140:1151 the mtDNA lesion accumulation 1123:1151 the mtDNA lesion accumulation observed in vivo Reducing Ogg1 O-GlcNAcylation in vivo by introducing a dominant negative O-GlcNAc transferase mutant (F460A) restored Ogg1 enzymatic activity and, consequently, reduced 8-OHdG and mtDNA damage despite the adverse hyperglycemic milieu 1123:1402 In vitro experiments demonstrated that O-GlcNAcylation inhibits Ogg1 activity, which could explain the mtDNA lesion accumulation observed in vivo Reducing Ogg1 O-GlcNAcylation in vivo by introducing a dominant negative O-GlcNAc transferase mutant (F460A) restored Ogg1 enzymatic activity and, consequently, reduced 8-OHdG and mtDNA damage despite the adverse hyperglycemic milieu. 27816939 7 57 located observed 1153:1160 arg2 accumulation 1140:1151 the mtDNA lesion accumulation 1123:1151 the mtDNA lesion accumulation observed in vivo Reducing Ogg1 O-GlcNAcylation in vivo by introducing a dominant negative O-GlcNAc transferase mutant (F460A) restored Ogg1 enzymatic activity and, consequently, reduced 8-OHdG and mtDNA damage despite the adverse hyperglycemic milieu 1123:1402 In vitro experiments demonstrated that O-GlcNAcylation inhibits Ogg1 activity, which could explain the mtDNA lesion accumulation observed in vivo Reducing Ogg1 O-GlcNAcylation in vivo by introducing a dominant negative O-GlcNAc transferase mutant (F460A) restored Ogg1 enzymatic activity and, consequently, reduced 8-OHdG and mtDNA damage despite the adverse hyperglycemic milieu. 27816939 7 57 located observed 1153:1160 arg1 O-GlcNAcylation 1184:1198 vivo Reducing Ogg1 O-GlcNAcylation 1165:1198 vivo Reducing Ogg1 O-GlcNAcylation 1165:1198 In vitro experiments demonstrated that O-GlcNAcylation inhibits Ogg1 activity, which could explain the mtDNA lesion accumulation observed in vivo Reducing Ogg1 O-GlcNAcylation in vivo by introducing a dominant negative O-GlcNAc transferase mutant (F460A) restored Ogg1 enzymatic activity and, consequently, reduced 8-OHdG and mtDNA damage despite the adverse hyperglycemic milieu. 27816939 7 58 theme negative 1234:1241 arg1 F460A 1272:1276 F460A 1272:1276 F460A 1272:1276 In vitro experiments demonstrated that O-GlcNAcylation inhibits Ogg1 activity, which could explain the mtDNA lesion accumulation observed in vivo Reducing Ogg1 O-GlcNAcylation in vivo by introducing a dominant negative O-GlcNAc transferase mutant (F460A) restored Ogg1 enzymatic activity and, consequently, reduced 8-OHdG and mtDNA damage despite the adverse hyperglycemic milieu. 27816939 7 58 theme negative 1234:1241 arg1 mutant 1264:1269 a dominant negative O-GlcNAc transferase mutant 1223:1269 a dominant negative O-GlcNAc transferase mutant (F460A) 1223:1277 In vitro experiments demonstrated that O-GlcNAcylation inhibits Ogg1 activity, which could explain the mtDNA lesion accumulation observed in vivo Reducing Ogg1 O-GlcNAcylation in vivo by introducing a dominant negative O-GlcNAc transferase mutant (F460A) restored Ogg1 enzymatic activity and, consequently, reduced 8-OHdG and mtDNA damage despite the adverse hyperglycemic milieu. 27816939 1 59 theme mtDNA 125:129 arg1 damage 131:136 mtDNA damage 125:136 mtDNA damage in cardiac myocytes resulting from increased oxidative stress 125:198 mtDNA damage in cardiac myocytes resulting from increased oxidative stress is emerging as an important factor in the pathogenesis of diabetic cardiomyopathy. 27816939 1 60 theme important 218:226 arg1 factor 228:233 an important factor 215:233 an important factor in the pathogenesis of diabetic cardiomyopathy 215:280 mtDNA damage in cardiac myocytes resulting from increased oxidative stress is emerging as an important factor in the pathogenesis of diabetic cardiomyopathy. 27816939 1 61 from factor 228:233 arg1 pathogenesis 242:253 the pathogenesis 238:253 the pathogenesis of diabetic cardiomyopathy 238:280 mtDNA damage in cardiac myocytes resulting from increased oxidative stress is emerging as an important factor in the pathogenesis of diabetic cardiomyopathy. 27816939 0 62 from Repair 98:103 arg1 Hearts 117:122 Diabetic Hearts 108:122 Diabetic Hearts 108:122 O-GlcNAcylation of 8-Oxoguanine DNA Glycosylase (Ogg1) Impairs Oxidative Mitochondrial DNA Lesion Repair in Diabetic Hearts. 27816939 5 63 theme damage 917:922 arg1 8-OHdG 877:882 8-OHdG 877:882 8-OHdG 877:882 In diabetic hearts, we further observed increased levels of 8-OHdG and an increased amount of mtDNA damage. 27816939 5 63 theme damage 917:922 arg1 levels 867:872 increased levels 857:872 increased levels of 8-OHdG 857:882 In diabetic hearts, we further observed increased levels of 8-OHdG and an increased amount of mtDNA damage. 27816939 5 63 theme damage 917:922 arg1 amount 901:906 an increased amount 888:906 an increased amount of mtDNA damage 888:922 In diabetic hearts, we further observed increased levels of 8-OHdG and an increased amount of mtDNA damage. 27816939 5 63 theme damage 917:922 arg1 damage 917:922 mtDNA damage 911:922 mtDNA damage 911:922 In diabetic hearts, we further observed increased levels of 8-OHdG and an increased amount of mtDNA damage. 27816939 4 64 theme increased 694:702 arg1 levels 717:722 increased Ogg1 protein levels 694:722 increased Ogg1 protein levels 694:722 Here we report that the hearts of type 1 diabetic mice, despite having increased Ogg1 protein levels, had significantly lower Ogg1 activity than the hearts of control, non-type 1 diabetic mice. 27816939 4 65 theme Ogg1 704:707 arg1 levels 717:722 increased Ogg1 protein levels 694:722 increased Ogg1 protein levels 694:722 Here we report that the hearts of type 1 diabetic mice, despite having increased Ogg1 protein levels, had significantly lower Ogg1 activity than the hearts of control, non-type 1 diabetic mice. 27816939 0 66 theme Oxidative 63:71 arg1 Repair 98:103 Oxidative Mitochondrial DNA Lesion Repair 63:103 Oxidative Mitochondrial DNA Lesion Repair in Diabetic Hearts 63:122 O-GlcNAcylation of 8-Oxoguanine DNA Glycosylase (Ogg1) Impairs Oxidative Mitochondrial DNA Lesion Repair in Diabetic Hearts. 27816939 8 67 theme Ogg1 1484:1487 arg1 O-GlcNAcylation 1465:1479 hyperglycemia-induced O-GlcNAcylation 1443:1479 hyperglycemia-induced O-GlcNAcylation of Ogg1 1443:1487 Taken together, our results implicate hyperglycemia-induced O-GlcNAcylation of Ogg1 in increased mtDNA damage and, therefore, provide a new plausible biochemical mechanism for diabetic cardiomyopathy. 27816939 6 68 from O-GlcNAcylated 968:981 arg1 mice 995:998 diabetic mice 986:998 diabetic mice 986:998 Interestingly, Ogg1 was found to be highly O-GlcNAcylated in diabetic mice compared with controls. 27816939 4 69 theme diabetic 664:671 arg1 mice 673:676 type 1 diabetic mice 657:676 type 1 diabetic mice 657:676 Here we report that the hearts of type 1 diabetic mice, despite having increased Ogg1 protein levels, had significantly lower Ogg1 activity than the hearts of control, non-type 1 diabetic mice. 27816939 8 70 theme mtDNA 1502:1506 arg1 damage 1508:1513 increased mtDNA damage 1492:1513 increased mtDNA damage 1492:1513 Taken together, our results implicate hyperglycemia-induced O-GlcNAcylation of Ogg1 in increased mtDNA damage and, therefore, provide a new plausible biochemical mechanism for diabetic cardiomyopathy. 27816939 7 71 theme lesion 1133:1138 arg1 accumulation 1140:1151 the mtDNA lesion accumulation 1123:1151 the mtDNA lesion accumulation observed in vivo Reducing Ogg1 O-GlcNAcylation in vivo by introducing a dominant negative O-GlcNAc transferase mutant (F460A) restored Ogg1 enzymatic activity and, consequently, reduced 8-OHdG and mtDNA damage despite the adverse hyperglycemic milieu 1123:1402 In vitro experiments demonstrated that O-GlcNAcylation inhibits Ogg1 activity, which could explain the mtDNA lesion accumulation observed in vivo Reducing Ogg1 O-GlcNAcylation in vivo by introducing a dominant negative O-GlcNAc transferase mutant (F460A) restored Ogg1 enzymatic activity and, consequently, reduced 8-OHdG and mtDNA damage despite the adverse hyperglycemic milieu. 27816939 7 72 theme O-GlcNAc 1243:1250 arg1 F460A 1272:1276 F460A 1272:1276 F460A 1272:1276 In vitro experiments demonstrated that O-GlcNAcylation inhibits Ogg1 activity, which could explain the mtDNA lesion accumulation observed in vivo Reducing Ogg1 O-GlcNAcylation in vivo by introducing a dominant negative O-GlcNAc transferase mutant (F460A) restored Ogg1 enzymatic activity and, consequently, reduced 8-OHdG and mtDNA damage despite the adverse hyperglycemic milieu. 27816939 7 72 theme O-GlcNAc 1243:1250 arg1 mutant 1264:1269 a dominant negative O-GlcNAc transferase mutant 1223:1269 a dominant negative O-GlcNAc transferase mutant (F460A) 1223:1277 In vitro experiments demonstrated that O-GlcNAcylation inhibits Ogg1 activity, which could explain the mtDNA lesion accumulation observed in vivo Reducing Ogg1 O-GlcNAcylation in vivo by introducing a dominant negative O-GlcNAc transferase mutant (F460A) restored Ogg1 enzymatic activity and, consequently, reduced 8-OHdG and mtDNA damage despite the adverse hyperglycemic milieu. 27816939 1 73 theme cardiac 141:147 arg1 myocytes 149:156 cardiac myocytes 141:156 cardiac myocytes resulting from increased oxidative stress 141:198 mtDNA damage in cardiac myocytes resulting from increased oxidative stress is emerging as an important factor in the pathogenesis of diabetic cardiomyopathy. 27816939 7 74 theme adverse 1375:1381 arg1 milieu 1397:1402 the adverse hyperglycemic milieu 1371:1402 the adverse hyperglycemic milieu 1371:1402 In vitro experiments demonstrated that O-GlcNAcylation inhibits Ogg1 activity, which could explain the mtDNA lesion accumulation observed in vivo Reducing Ogg1 O-GlcNAcylation in vivo by introducing a dominant negative O-GlcNAc transferase mutant (F460A) restored Ogg1 enzymatic activity and, consequently, reduced 8-OHdG and mtDNA damage despite the adverse hyperglycemic milieu. 27816939 7 75 theme Ogg1 1179:1182 arg1 O-GlcNAcylation 1184:1198 vivo Reducing Ogg1 O-GlcNAcylation 1165:1198 vivo Reducing Ogg1 O-GlcNAcylation 1165:1198 In vitro experiments demonstrated that O-GlcNAcylation inhibits Ogg1 activity, which could explain the mtDNA lesion accumulation observed in vivo Reducing Ogg1 O-GlcNAcylation in vivo by introducing a dominant negative O-GlcNAc transferase mutant (F460A) restored Ogg1 enzymatic activity and, consequently, reduced 8-OHdG and mtDNA damage despite the adverse hyperglycemic milieu. 27434817 4 0 theme X-ray 715:719 arg1 crystallography 721:735 X-ray crystallography 715:735 X-ray crystallography 715:735 Using circular dichroism, NMR spectroscopy, native mass-spectrometry and X-ray crystallography, we studied how bundle formation was affected by systematic replacement of the hydrophobic surface of the oligourea helix with either polar or different hydrophobic side chains. 27434817 4 1 theme side 902:905 arg1 chains 907:912 either polar or different hydrophobic side chains 864:912 either polar or different hydrophobic side chains 864:912 Using circular dichroism, NMR spectroscopy, native mass-spectrometry and X-ray crystallography, we studied how bundle formation was affected by systematic replacement of the hydrophobic surface of the oligourea helix with either polar or different hydrophobic side chains. 27434817 5 2 theme aqueous 1026:1032 arg1 conditions 1034:1043 aqueous conditions 1026:1043 aqueous conditions 1026:1043 The molecular information gathered here has revealed several key requirements for foldamer bundle formation in aqueous conditions, and provides valuable insight toward the development of foldamer quaternary assemblies with improved (bio)physical properties and divergent topologies. 27434817 5 3 from formation 1013:1021 arg1 conditions 1034:1043 aqueous conditions 1026:1043 aqueous conditions 1026:1043 The molecular information gathered here has revealed several key requirements for foldamer bundle formation in aqueous conditions, and provides valuable insight toward the development of foldamer quaternary assemblies with improved (bio)physical properties and divergent topologies. 27434817 4 4 theme hydrophobic 816:826 arg1 surface 828:834 the hydrophobic surface 812:834 the hydrophobic surface of the oligourea helix 812:857 Using circular dichroism, NMR spectroscopy, native mass-spectrometry and X-ray crystallography, we studied how bundle formation was affected by systematic replacement of the hydrophobic surface of the oligourea helix with either polar or different hydrophobic side chains. 27434817 1 5 theme synthetic 54:62 arg1 oligomers 64:72 Non-natural synthetic oligomers 42:72 Non-natural synthetic oligomers that adopt well-defined secondary structures (i.e., foldamers) 42:135 Non-natural synthetic oligomers that adopt well-defined secondary structures (i.e., foldamers) represent appealing components for the fabrication of bioinspired self-assembled architectures at the nanometer scale. 27434817 5 6 theme bundle 1006:1011 arg1 formation 1013:1021 foldamer bundle formation 997:1021 foldamer bundle formation in aqueous conditions 997:1043 The molecular information gathered here has revealed several key requirements for foldamer bundle formation in aqueous conditions, and provides valuable insight toward the development of foldamer quaternary assemblies with improved (bio)physical properties and divergent topologies. 27434817 4 7 theme circular 648:655 arg1 dichroism 657:665 circular dichroism 648:665 circular dichroism 648:665 Using circular dichroism, NMR spectroscopy, native mass-spectrometry and X-ray crystallography, we studied how bundle formation was affected by systematic replacement of the hydrophobic surface of the oligourea helix with either polar or different hydrophobic side chains. 27434817 4 8 theme systematic 786:795 arg1 replacement 797:807 systematic replacement 786:807 systematic replacement of the hydrophobic surface of the oligourea helix with either polar or different hydrophobic side chains 786:912 Using circular dichroism, NMR spectroscopy, native mass-spectrometry and X-ray crystallography, we studied how bundle formation was affected by systematic replacement of the hydrophobic surface of the oligourea helix with either polar or different hydrophobic side chains. 27434817 3 9 theme bundle 487:492 arg1 formation 494:502 oligourea helix bundle formation 471:502 oligourea helix bundle formation 471:502 In order to gain better insight into the determinants of oligourea helix bundle formation, we have investigated the sequence-to-structure relationship of an 11-mer oligourea previously shown to assemble into a six-helix bundle. 27434817 5 10 theme physical 1152:1159 arg1 properties 1161:1170 improved (bio)physical properties 1138:1170 improved (bio)physical properties 1138:1170 The molecular information gathered here has revealed several key requirements for foldamer bundle formation in aqueous conditions, and provides valuable insight toward the development of foldamer quaternary assemblies with improved (bio)physical properties and divergent topologies. 27434817 3 11 theme oligourea 471:479 arg1 formation 494:502 oligourea helix bundle formation 471:502 oligourea helix bundle formation 471:502 In order to gain better insight into the determinants of oligourea helix bundle formation, we have investigated the sequence-to-structure relationship of an 11-mer oligourea previously shown to assemble into a six-helix bundle. 27434817 2 12 theme oligourea 293:301 arg1 helices 303:309 peptidomimetic N,N'-linked oligourea helices 266:309 helices 303:309 Recently, peptidomimetic N,N'-linked oligourea helices have been designed de novo with the ability to fold into discrete helix bundles in aqueous conditions. 27434817 5 13 theme several 968:974 arg1 requirements 980:991 several key requirements 968:991 several key requirements for foldamer bundle formation in aqueous conditions 968:1043 The molecular information gathered here has revealed several key requirements for foldamer bundle formation in aqueous conditions, and provides valuable insight toward the development of foldamer quaternary assemblies with improved (bio)physical properties and divergent topologies. 27434817 4 14 theme polar 871:875 arg1 chains 907:912 either polar or different hydrophobic side chains 864:912 either polar or different hydrophobic side chains 864:912 Using circular dichroism, NMR spectroscopy, native mass-spectrometry and X-ray crystallography, we studied how bundle formation was affected by systematic replacement of the hydrophobic surface of the oligourea helix with either polar or different hydrophobic side chains. 27434817 1 15 dep foldamers 126:134 arg1 i.e. 120:123 i.e. 120:123 i.e. 120:123 Non-natural synthetic oligomers that adopt well-defined secondary structures (i.e., foldamers) represent appealing components for the fabrication of bioinspired self-assembled architectures at the nanometer scale. 27434817 2 16 theme N'-linked 283:291 arg1 helices 303:309 peptidomimetic N,N'-linked oligourea helices 266:309 helices 303:309 Recently, peptidomimetic N,N'-linked oligourea helices have been designed de novo with the ability to fold into discrete helix bundles in aqueous conditions. 27434817 2 17 theme aqueous 394:400 arg1 conditions 402:411 aqueous conditions 394:411 aqueous conditions 394:411 Recently, peptidomimetic N,N'-linked oligourea helices have been designed de novo with the ability to fold into discrete helix bundles in aqueous conditions. 27434817 4 18 theme hydrophobic 890:900 arg1 chains 907:912 either polar or different hydrophobic side chains 864:912 either polar or different hydrophobic side chains 864:912 Using circular dichroism, NMR spectroscopy, native mass-spectrometry and X-ray crystallography, we studied how bundle formation was affected by systematic replacement of the hydrophobic surface of the oligourea helix with either polar or different hydrophobic side chains. 27434817 1 19 theme well-defined 85:96 arg1 foldamers 126:134 foldamers 126:134 foldamers 126:134 Non-natural synthetic oligomers that adopt well-defined secondary structures (i.e., foldamers) represent appealing components for the fabrication of bioinspired self-assembled architectures at the nanometer scale. 27434817 1 19 theme well-defined 85:96 arg1 structures 108:117 well-defined secondary structures 85:117 well-defined secondary structures (i.e., foldamers) 85:135 Non-natural synthetic oligomers that adopt well-defined secondary structures (i.e., foldamers) represent appealing components for the fabrication of bioinspired self-assembled architectures at the nanometer scale. 27434817 4 20 theme different 880:888 arg1 chains 907:912 either polar or different hydrophobic side chains 864:912 either polar or different hydrophobic side chains 864:912 Using circular dichroism, NMR spectroscopy, native mass-spectrometry and X-ray crystallography, we studied how bundle formation was affected by systematic replacement of the hydrophobic surface of the oligourea helix with either polar or different hydrophobic side chains. 27434817 1 21 theme secondary 98:106 arg1 foldamers 126:134 foldamers 126:134 foldamers 126:134 Non-natural synthetic oligomers that adopt well-defined secondary structures (i.e., foldamers) represent appealing components for the fabrication of bioinspired self-assembled architectures at the nanometer scale. 27434817 1 21 theme secondary 98:106 arg1 structures 108:117 well-defined secondary structures 85:117 well-defined secondary structures (i.e., foldamers) 85:135 Non-natural synthetic oligomers that adopt well-defined secondary structures (i.e., foldamers) represent appealing components for the fabrication of bioinspired self-assembled architectures at the nanometer scale. 27434817 1 22 theme bioinspired 191:201 arg1 architectures 218:230 bioinspired self-assembled architectures 191:230 bioinspired self-assembled architectures 191:230 Non-natural synthetic oligomers that adopt well-defined secondary structures (i.e., foldamers) represent appealing components for the fabrication of bioinspired self-assembled architectures at the nanometer scale. 27434817 0 23 theme Oligourea 14:22 arg1 Bundle 34:39 an Oligourea Six-Helix Bundle 11:39 an Oligourea Six-Helix Bundle 11:39 Anatomy of an Oligourea Six-Helix Bundle. 27434817 2 24 link N'-linked 283:291 arg1 helices 303:309 peptidomimetic N,N'-linked oligourea helices 266:309 helices 303:309 Recently, peptidomimetic N,N'-linked oligourea helices have been designed de novo with the ability to fold into discrete helix bundles in aqueous conditions. 27434817 5 25 theme key 976:978 arg1 requirements 980:991 several key requirements 968:991 several key requirements for foldamer bundle formation in aqueous conditions 968:1043 The molecular information gathered here has revealed several key requirements for foldamer bundle formation in aqueous conditions, and provides valuable insight toward the development of foldamer quaternary assemblies with improved (bio)physical properties and divergent topologies. 27434817 3 26 theme 11-mer 571:576 arg1 oligourea 578:586 an 11-mer oligourea 568:586 an 11-mer oligourea previously shown to assemble into a six-helix bundle 568:639 In order to gain better insight into the determinants of oligourea helix bundle formation, we have investigated the sequence-to-structure relationship of an 11-mer oligourea previously shown to assemble into a six-helix bundle. 27434817 1 27 theme self-assembled 203:216 arg1 architectures 218:230 bioinspired self-assembled architectures 191:230 bioinspired self-assembled architectures 191:230 Non-natural synthetic oligomers that adopt well-defined secondary structures (i.e., foldamers) represent appealing components for the fabrication of bioinspired self-assembled architectures at the nanometer scale. 27434817 4 28 with replacement 797:807 arg1 chains 907:912 either polar or different hydrophobic side chains 864:912 either polar or different hydrophobic side chains 864:912 Using circular dichroism, NMR spectroscopy, native mass-spectrometry and X-ray crystallography, we studied how bundle formation was affected by systematic replacement of the hydrophobic surface of the oligourea helix with either polar or different hydrophobic side chains. 27434817 3 29 theme sequence-to-structure 530:550 arg1 relationship 552:563 the sequence-to-structure relationship 526:563 the sequence-to-structure relationship of an 11-mer oligourea previously shown to assemble into a six-helix bundle 526:639 In order to gain better insight into the determinants of oligourea helix bundle formation, we have investigated the sequence-to-structure relationship of an 11-mer oligourea previously shown to assemble into a six-helix bundle. 27434817 3 30 theme oligourea 578:586 arg1 relationship 552:563 the sequence-to-structure relationship 526:563 the sequence-to-structure relationship of an 11-mer oligourea previously shown to assemble into a six-helix bundle 526:639 In order to gain better insight into the determinants of oligourea helix bundle formation, we have investigated the sequence-to-structure relationship of an 11-mer oligourea previously shown to assemble into a six-helix bundle. 27434817 1 31 theme architectures 218:230 arg1 fabrication 176:186 the fabrication 172:186 the fabrication of bioinspired self-assembled architectures at the nanometer scale 172:253 Non-natural synthetic oligomers that adopt well-defined secondary structures (i.e., foldamers) represent appealing components for the fabrication of bioinspired self-assembled architectures at the nanometer scale. 27434817 0 32 theme Bundle 34:39 arg1 Anatomy 0:6 Anatomy 0:6 Anatomy of an Oligourea Six-Helix Bundle 0:39 Anatomy of an Oligourea Six-Helix Bundle. 27434817 5 33 with assemblies 1122:1131 arg1 properties 1161:1170 improved (bio)physical properties 1138:1170 improved (bio)physical properties 1138:1170 The molecular information gathered here has revealed several key requirements for foldamer bundle formation in aqueous conditions, and provides valuable insight toward the development of foldamer quaternary assemblies with improved (bio)physical properties and divergent topologies. 27434817 5 33 with assemblies 1122:1131 arg1 topologies 1186:1195 divergent topologies 1176:1195 divergent topologies 1176:1195 The molecular information gathered here has revealed several key requirements for foldamer bundle formation in aqueous conditions, and provides valuable insight toward the development of foldamer quaternary assemblies with improved (bio)physical properties and divergent topologies. 27434817 5 34 theme improved 1138:1145 arg1 properties 1161:1170 improved (bio)physical properties 1138:1170 improved (bio)physical properties 1138:1170 The molecular information gathered here has revealed several key requirements for foldamer bundle formation in aqueous conditions, and provides valuable insight toward the development of foldamer quaternary assemblies with improved (bio)physical properties and divergent topologies. 27434817 4 35 theme helix 853:857 arg1 surface 828:834 the hydrophobic surface 812:834 the hydrophobic surface of the oligourea helix 812:857 Using circular dichroism, NMR spectroscopy, native mass-spectrometry and X-ray crystallography, we studied how bundle formation was affected by systematic replacement of the hydrophobic surface of the oligourea helix with either polar or different hydrophobic side chains. 27434817 3 36 theme better 431:436 arg1 insight 438:444 better insight 431:444 better insight into the determinants of oligourea helix bundle formation 431:502 In order to gain better insight into the determinants of oligourea helix bundle formation, we have investigated the sequence-to-structure relationship of an 11-mer oligourea previously shown to assemble into a six-helix bundle. 27434817 4 37 theme NMR 668:670 arg1 spectroscopy 672:683 NMR spectroscopy 668:683 NMR spectroscopy 668:683 Using circular dichroism, NMR spectroscopy, native mass-spectrometry and X-ray crystallography, we studied how bundle formation was affected by systematic replacement of the hydrophobic surface of the oligourea helix with either polar or different hydrophobic side chains. 27434817 0 38 theme Six-Helix 24:32 arg1 Bundle 34:39 an Oligourea Six-Helix Bundle 11:39 an Oligourea Six-Helix Bundle 11:39 Anatomy of an Oligourea Six-Helix Bundle. 27434817 4 39 theme oligourea 843:851 arg1 helix 853:857 the oligourea helix 839:857 the oligourea helix 839:857 Using circular dichroism, NMR spectroscopy, native mass-spectrometry and X-ray crystallography, we studied how bundle formation was affected by systematic replacement of the hydrophobic surface of the oligourea helix with either polar or different hydrophobic side chains. 27434817 5 40 theme molecular 919:927 arg1 information 929:939 The molecular information 915:939 The molecular information gathered here 915:953 The molecular information gathered here has revealed several key requirements for foldamer bundle formation in aqueous conditions, and provides valuable insight toward the development of foldamer quaternary assemblies with improved (bio)physical properties and divergent topologies. 27434817 5 41 theme bio 1148:1150 arg1 properties 1161:1170 improved (bio)physical properties 1138:1170 improved (bio)physical properties 1138:1170 The molecular information gathered here has revealed several key requirements for foldamer bundle formation in aqueous conditions, and provides valuable insight toward the development of foldamer quaternary assemblies with improved (bio)physical properties and divergent topologies. 27434817 2 42 from bundles 383:389 arg1 conditions 402:411 aqueous conditions 394:411 aqueous conditions 394:411 Recently, peptidomimetic N,N'-linked oligourea helices have been designed de novo with the ability to fold into discrete helix bundles in aqueous conditions. 27434817 3 43 theme formation 494:502 arg1 determinants 455:466 the determinants 451:466 the determinants of oligourea helix bundle formation 451:502 In order to gain better insight into the determinants of oligourea helix bundle formation, we have investigated the sequence-to-structure relationship of an 11-mer oligourea previously shown to assemble into a six-helix bundle. 27434817 5 44 theme foldamer 997:1004 arg1 formation 1013:1021 foldamer bundle formation 997:1021 foldamer bundle formation in aqueous conditions 997:1043 The molecular information gathered here has revealed several key requirements for foldamer bundle formation in aqueous conditions, and provides valuable insight toward the development of foldamer quaternary assemblies with improved (bio)physical properties and divergent topologies. 27434817 4 45 theme native 686:691 arg1 mass-spectrometry 693:709 native mass-spectrometry 686:709 native mass-spectrometry 686:709 Using circular dichroism, NMR spectroscopy, native mass-spectrometry and X-ray crystallography, we studied how bundle formation was affected by systematic replacement of the hydrophobic surface of the oligourea helix with either polar or different hydrophobic side chains. 27434817 5 46 theme valuable 1059:1066 arg1 insight 1068:1074 valuable insight 1059:1074 valuable insight toward the development of foldamer quaternary assemblies with improved (bio)physical properties and divergent topologies 1059:1195 The molecular information gathered here has revealed several key requirements for foldamer bundle formation in aqueous conditions, and provides valuable insight toward the development of foldamer quaternary assemblies with improved (bio)physical properties and divergent topologies. 27434817 5 47 theme foldamer 1102:1109 arg1 assemblies 1122:1131 foldamer quaternary assemblies 1102:1131 foldamer quaternary assemblies with improved (bio)physical properties and divergent topologies 1102:1195 The molecular information gathered here has revealed several key requirements for foldamer bundle formation in aqueous conditions, and provides valuable insight toward the development of foldamer quaternary assemblies with improved (bio)physical properties and divergent topologies. 27434817 4 48 theme surface 828:834 arg1 replacement 797:807 systematic replacement 786:807 systematic replacement of the hydrophobic surface of the oligourea helix with either polar or different hydrophobic side chains 786:912 Using circular dichroism, NMR spectroscopy, native mass-spectrometry and X-ray crystallography, we studied how bundle formation was affected by systematic replacement of the hydrophobic surface of the oligourea helix with either polar or different hydrophobic side chains. 27434817 3 49 theme helix 481:485 arg1 formation 494:502 oligourea helix bundle formation 471:502 oligourea helix bundle formation 471:502 In order to gain better insight into the determinants of oligourea helix bundle formation, we have investigated the sequence-to-structure relationship of an 11-mer oligourea previously shown to assemble into a six-helix bundle. 27434817 3 50 theme six-helix 624:632 arg1 bundle 634:639 a six-helix bundle 622:639 a six-helix bundle 622:639 In order to gain better insight into the determinants of oligourea helix bundle formation, we have investigated the sequence-to-structure relationship of an 11-mer oligourea previously shown to assemble into a six-helix bundle. 27434817 1 51 theme nanometer 239:247 arg1 scale 249:253 the nanometer scale 235:253 the nanometer scale 235:253 Non-natural synthetic oligomers that adopt well-defined secondary structures (i.e., foldamers) represent appealing components for the fabrication of bioinspired self-assembled architectures at the nanometer scale. 27434817 1 52 from scale 249:253 arg1 fabrication 176:186 the fabrication 172:186 the fabrication of bioinspired self-assembled architectures at the nanometer scale 172:253 Non-natural synthetic oligomers that adopt well-defined secondary structures (i.e., foldamers) represent appealing components for the fabrication of bioinspired self-assembled architectures at the nanometer scale. 27434817 5 53 theme quaternary 1111:1120 arg1 assemblies 1122:1131 foldamer quaternary assemblies 1102:1131 foldamer quaternary assemblies with improved (bio)physical properties and divergent topologies 1102:1195 The molecular information gathered here has revealed several key requirements for foldamer bundle formation in aqueous conditions, and provides valuable insight toward the development of foldamer quaternary assemblies with improved (bio)physical properties and divergent topologies. 27434817 2 54 theme N 281:281 arg1 helices 303:309 peptidomimetic N,N'-linked oligourea helices 266:309 helices 303:309 Recently, peptidomimetic N,N'-linked oligourea helices have been designed de novo with the ability to fold into discrete helix bundles in aqueous conditions. 27434817 1 55 theme appealing 147:155 arg1 components 157:166 appealing components 147:166 appealing components for the fabrication of bioinspired self-assembled architectures at the nanometer scale 147:253 Non-natural synthetic oligomers that adopt well-defined secondary structures (i.e., foldamers) represent appealing components for the fabrication of bioinspired self-assembled architectures at the nanometer scale. 27434817 4 56 theme bundle 753:758 arg1 formation 760:768 bundle formation 753:768 bundle formation 753:768 Using circular dichroism, NMR spectroscopy, native mass-spectrometry and X-ray crystallography, we studied how bundle formation was affected by systematic replacement of the hydrophobic surface of the oligourea helix with either polar or different hydrophobic side chains. 27434817 5 57 theme assemblies 1122:1131 arg1 development 1087:1097 the development 1083:1097 the development of foldamer quaternary assemblies with improved (bio)physical properties and divergent topologies 1083:1195 The molecular information gathered here has revealed several key requirements for foldamer bundle formation in aqueous conditions, and provides valuable insight toward the development of foldamer quaternary assemblies with improved (bio)physical properties and divergent topologies. 27434817 2 58 theme peptidomimetic 266:279 arg1 helices 303:309 peptidomimetic N,N'-linked oligourea helices 266:309 helices 303:309 Recently, peptidomimetic N,N'-linked oligourea helices have been designed de novo with the ability to fold into discrete helix bundles in aqueous conditions. 27434817 2 59 theme helix 377:381 arg1 bundles 383:389 discrete helix bundles 368:389 discrete helix bundles in aqueous conditions 368:411 Recently, peptidomimetic N,N'-linked oligourea helices have been designed de novo with the ability to fold into discrete helix bundles in aqueous conditions. 27434817 5 60 theme divergent 1176:1184 arg1 topologies 1186:1195 divergent topologies 1176:1195 divergent topologies 1176:1195 The molecular information gathered here has revealed several key requirements for foldamer bundle formation in aqueous conditions, and provides valuable insight toward the development of foldamer quaternary assemblies with improved (bio)physical properties and divergent topologies. 27434817 1 61 theme Non-natural 42:52 arg1 oligomers 64:72 Non-natural synthetic oligomers 42:72 Non-natural synthetic oligomers that adopt well-defined secondary structures (i.e., foldamers) 42:135 Non-natural synthetic oligomers that adopt well-defined secondary structures (i.e., foldamers) represent appealing components for the fabrication of bioinspired self-assembled architectures at the nanometer scale. 27434817 2 62 theme discrete 368:375 arg1 bundles 383:389 discrete helix bundles 368:389 discrete helix bundles in aqueous conditions 368:411 Recently, peptidomimetic N,N'-linked oligourea helices have been designed de novo with the ability to fold into discrete helix bundles in aqueous conditions. 28451332 3 0 theme mass 717:720 arg1 spectrometry 722:733 nano-UHPLC-tandem mass spectrometry 699:733 nano-UHPLC-tandem mass spectrometry 699:733 Preparation of a proteolytic fragment of Pseudomonas aeruginosa EF-P bearing both α- and β-rhamnosylated arginine enabled the unequivocal determination of the native glycosidic linkage to be α through 2D NMR and nano-UHPLC-tandem mass spectrometry studies. 28451332 1 1 theme protein 152:158 arg1 glycosylation 160:172 N-linked protein glycosylation 143:172 N-linked protein glycosylation 143:172 A new class of N-linked protein glycosylation - arginine rhamnosylation - has recently been discovered as a critical modification for the function of bacterial elongation factor P (EF-P). 28451332 0 2 theme linkage 86:92 arg1 Synthesis 0:8 Synthesis 0:8 Synthesis of rhamnosylated arginine glycopeptides 0:48 Synthesis of rhamnosylated arginine glycopeptides and determination of the glycosidic linkage in bacterial elongation factor P. 28451332 0 2 theme linkage 86:92 arg1 determination 54:66 determination 54:66 determination of the glycosidic linkage in bacterial elongation factor P 54:125 Synthesis of rhamnosylated arginine glycopeptides and determination of the glycosidic linkage in bacterial elongation factor P. 28451332 1 3 theme glycosylation 160:172 arg1 class 134:138 A new class 128:138 A new class of N-linked protein glycosylation - arginine rhamnosylation - 128:200 A new class of N-linked protein glycosylation - arginine rhamnosylation - has recently been discovered as a critical modification for the function of bacterial elongation factor P (EF-P). 28451332 1 3 theme glycosylation 160:172 arg1 modification 245:256 a critical modification 234:256 a critical modification for the function of bacterial elongation factor P (EF-P) 234:313 A new class of N-linked protein glycosylation - arginine rhamnosylation - has recently been discovered as a critical modification for the function of bacterial elongation factor P (EF-P). 28451332 0 4 theme elongation 107:116 arg1 P 125:125 bacterial elongation factor P 97:125 bacterial elongation factor P 97:125 Synthesis of rhamnosylated arginine glycopeptides and determination of the glycosidic linkage in bacterial elongation factor P. 28451332 0 5 from Synthesis 0:8 arg1 P 125:125 bacterial elongation factor P 97:125 bacterial elongation factor P 97:125 Synthesis of rhamnosylated arginine glycopeptides and determination of the glycosidic linkage in bacterial elongation factor P. 28451332 3 6 theme aeruginosa 540:549 arg1 fragment 516:523 a proteolytic fragment 502:523 a proteolytic fragment of Pseudomonas aeruginosa EF-P bearing both α- and β-rhamnosylated arginine 502:599 Preparation of a proteolytic fragment of Pseudomonas aeruginosa EF-P bearing both α- and β-rhamnosylated arginine enabled the unequivocal determination of the native glycosidic linkage to be α through 2D NMR and nano-UHPLC-tandem mass spectrometry studies. 28451332 0 7 theme bacterial 97:105 arg1 P 125:125 bacterial elongation factor P 97:125 bacterial elongation factor P 97:125 Synthesis of rhamnosylated arginine glycopeptides and determination of the glycosidic linkage in bacterial elongation factor P. 28451332 1 8 dep class 134:138 arg1 rhamnosylation 185:198 arginine rhamnosylation 176:198 A new class of N-linked protein glycosylation - arginine rhamnosylation - 128:200 A new class of N-linked protein glycosylation - arginine rhamnosylation - has recently been discovered as a critical modification for the function of bacterial elongation factor P (EF-P). 28451332 0 9 from determination 54:66 arg1 P 125:125 bacterial elongation factor P 97:125 bacterial elongation factor P 97:125 Synthesis of rhamnosylated arginine glycopeptides and determination of the glycosidic linkage in bacterial elongation factor P. 28451332 2 10 theme β-rhamnosylated 379:393 arg1 cassettes 416:424 suitably protected α- and β-rhamnosylated arginine amino acid "cassettes" 353:425 suitably protected α- and β-rhamnosylated arginine amino acid "cassettes" that can be directly installed into rhamnosylated peptides 353:484 Herein, we describe the synthesis of suitably protected α- and β-rhamnosylated arginine amino acid "cassettes" that can be directly installed into rhamnosylated peptides. 28451332 0 11 theme factor 118:123 arg1 P 125:125 bacterial elongation factor P 97:125 bacterial elongation factor P 97:125 Synthesis of rhamnosylated arginine glycopeptides and determination of the glycosidic linkage in bacterial elongation factor P. 28451332 1 12 theme arginine 176:183 arg1 rhamnosylation 185:198 arginine rhamnosylation 176:198 A new class of N-linked protein glycosylation - arginine rhamnosylation - 128:200 A new class of N-linked protein glycosylation - arginine rhamnosylation - has recently been discovered as a critical modification for the function of bacterial elongation factor P (EF-P). 28451332 2 13 theme rhamnosylated 463:475 arg1 peptides 477:484 rhamnosylated peptides 463:484 rhamnosylated peptides 463:484 Herein, we describe the synthesis of suitably protected α- and β-rhamnosylated arginine amino acid "cassettes" that can be directly installed into rhamnosylated peptides. 28451332 3 14 dep NMR 691:693 arg1 studies 735:741 studies 735:741 studies 735:741 Preparation of a proteolytic fragment of Pseudomonas aeruginosa EF-P bearing both α- and β-rhamnosylated arginine enabled the unequivocal determination of the native glycosidic linkage to be α through 2D NMR and nano-UHPLC-tandem mass spectrometry studies. 28451332 3 15 theme α- 569:570 arg1 arginine 592:599 both α- and β-rhamnosylated arginine 564:599 both α- and β-rhamnosylated arginine 564:599 Preparation of a proteolytic fragment of Pseudomonas aeruginosa EF-P bearing both α- and β-rhamnosylated arginine enabled the unequivocal determination of the native glycosidic linkage to be α through 2D NMR and nano-UHPLC-tandem mass spectrometry studies. 28451332 2 16 theme α- 372:373 arg1 cassettes 416:424 suitably protected α- and β-rhamnosylated arginine amino acid "cassettes" 353:425 suitably protected α- and β-rhamnosylated arginine amino acid "cassettes" that can be directly installed into rhamnosylated peptides 353:484 Herein, we describe the synthesis of suitably protected α- and β-rhamnosylated arginine amino acid "cassettes" that can be directly installed into rhamnosylated peptides. 28451332 1 17 theme bacterial 278:286 arg1 factor 299:304 bacterial elongation factor 278:304 bacterial elongation factor P (EF-P) 278:313 A new class of N-linked protein glycosylation - arginine rhamnosylation - has recently been discovered as a critical modification for the function of bacterial elongation factor P (EF-P). 28451332 2 18 theme protected 362:370 arg1 cassettes 416:424 suitably protected α- and β-rhamnosylated arginine amino acid "cassettes" 353:425 suitably protected α- and β-rhamnosylated arginine amino acid "cassettes" that can be directly installed into rhamnosylated peptides 353:484 Herein, we describe the synthesis of suitably protected α- and β-rhamnosylated arginine amino acid "cassettes" that can be directly installed into rhamnosylated peptides. 28451332 0 19 theme arginine 27:34 arg1 glycopeptides 36:48 rhamnosylated arginine glycopeptides 13:48 rhamnosylated arginine glycopeptides 13:48 Synthesis of rhamnosylated arginine glycopeptides and determination of the glycosidic linkage in bacterial elongation factor P. 28451332 1 20 theme elongation 288:297 arg1 factor 299:304 bacterial elongation factor 278:304 bacterial elongation factor P (EF-P) 278:313 A new class of N-linked protein glycosylation - arginine rhamnosylation - has recently been discovered as a critical modification for the function of bacterial elongation factor P (EF-P). 28451332 0 21 theme rhamnosylated 13:25 arg1 glycopeptides 36:48 rhamnosylated arginine glycopeptides 13:48 rhamnosylated arginine glycopeptides 13:48 Synthesis of rhamnosylated arginine glycopeptides and determination of the glycosidic linkage in bacterial elongation factor P. 28451332 1 22 theme factor 299:304 arg1 function 266:273 the function 262:273 the function of bacterial elongation factor P (EF-P) 262:313 A new class of N-linked protein glycosylation - arginine rhamnosylation - has recently been discovered as a critical modification for the function of bacterial elongation factor P (EF-P). 28451332 3 23 theme linkage 664:670 arg1 determination 625:637 the unequivocal determination 609:637 the unequivocal determination of the native glycosidic linkage 609:670 Preparation of a proteolytic fragment of Pseudomonas aeruginosa EF-P bearing both α- and β-rhamnosylated arginine enabled the unequivocal determination of the native glycosidic linkage to be α through 2D NMR and nano-UHPLC-tandem mass spectrometry studies. 28451332 2 24 theme acid 410:413 arg1 cassettes 416:424 suitably protected α- and β-rhamnosylated arginine amino acid "cassettes" 353:425 suitably protected α- and β-rhamnosylated arginine amino acid "cassettes" that can be directly installed into rhamnosylated peptides 353:484 Herein, we describe the synthesis of suitably protected α- and β-rhamnosylated arginine amino acid "cassettes" that can be directly installed into rhamnosylated peptides. 28451332 0 25 from linkage 86:92 arg1 P 125:125 bacterial elongation factor P 97:125 bacterial elongation factor P 97:125 Synthesis of rhamnosylated arginine glycopeptides and determination of the glycosidic linkage in bacterial elongation factor P. 28451332 2 26 theme amino 404:408 arg1 cassettes 416:424 suitably protected α- and β-rhamnosylated arginine amino acid "cassettes" 353:425 suitably protected α- and β-rhamnosylated arginine amino acid "cassettes" that can be directly installed into rhamnosylated peptides 353:484 Herein, we describe the synthesis of suitably protected α- and β-rhamnosylated arginine amino acid "cassettes" that can be directly installed into rhamnosylated peptides. 28451332 0 27 theme glycopeptides 36:48 arg1 Synthesis 0:8 Synthesis 0:8 Synthesis of rhamnosylated arginine glycopeptides 0:48 Synthesis of rhamnosylated arginine glycopeptides and determination of the glycosidic linkage in bacterial elongation factor P. 28451332 0 27 theme glycopeptides 36:48 arg1 determination 54:66 determination 54:66 determination of the glycosidic linkage in bacterial elongation factor P 54:125 Synthesis of rhamnosylated arginine glycopeptides and determination of the glycosidic linkage in bacterial elongation factor P. 28451332 1 28 link N-linked 143:150 arg1 glycosylation 160:172 N-linked protein glycosylation 143:172 N-linked protein glycosylation 143:172 A new class of N-linked protein glycosylation - arginine rhamnosylation - has recently been discovered as a critical modification for the function of bacterial elongation factor P (EF-P). 28451332 3 29 theme native 646:651 arg1 linkage 664:670 the native glycosidic linkage 642:670 the native glycosidic linkage 642:670 Preparation of a proteolytic fragment of Pseudomonas aeruginosa EF-P bearing both α- and β-rhamnosylated arginine enabled the unequivocal determination of the native glycosidic linkage to be α through 2D NMR and nano-UHPLC-tandem mass spectrometry studies. 28451332 2 30 theme arginine 395:402 arg1 cassettes 416:424 suitably protected α- and β-rhamnosylated arginine amino acid "cassettes" 353:425 suitably protected α- and β-rhamnosylated arginine amino acid "cassettes" that can be directly installed into rhamnosylated peptides 353:484 Herein, we describe the synthesis of suitably protected α- and β-rhamnosylated arginine amino acid "cassettes" that can be directly installed into rhamnosylated peptides. 28451332 3 31 theme glycosidic 653:662 arg1 linkage 664:670 the native glycosidic linkage 642:670 the native glycosidic linkage 642:670 Preparation of a proteolytic fragment of Pseudomonas aeruginosa EF-P bearing both α- and β-rhamnosylated arginine enabled the unequivocal determination of the native glycosidic linkage to be α through 2D NMR and nano-UHPLC-tandem mass spectrometry studies. 28451332 3 32 theme β-rhamnosylated 576:590 arg1 arginine 592:599 both α- and β-rhamnosylated arginine 564:599 both α- and β-rhamnosylated arginine 564:599 Preparation of a proteolytic fragment of Pseudomonas aeruginosa EF-P bearing both α- and β-rhamnosylated arginine enabled the unequivocal determination of the native glycosidic linkage to be α through 2D NMR and nano-UHPLC-tandem mass spectrometry studies. 28451332 3 33 theme nano-UHPLC-tandem 699:715 arg1 spectrometry 722:733 nano-UHPLC-tandem mass spectrometry 699:733 nano-UHPLC-tandem mass spectrometry 699:733 Preparation of a proteolytic fragment of Pseudomonas aeruginosa EF-P bearing both α- and β-rhamnosylated arginine enabled the unequivocal determination of the native glycosidic linkage to be α through 2D NMR and nano-UHPLC-tandem mass spectrometry studies. 28451332 0 34 from P 125:125 arg1 Synthesis 0:8 Synthesis 0:8 Synthesis of rhamnosylated arginine glycopeptides 0:48 Synthesis of rhamnosylated arginine glycopeptides and determination of the glycosidic linkage in bacterial elongation factor P. 28451332 0 34 from P 125:125 arg1 determination 54:66 determination 54:66 determination of the glycosidic linkage in bacterial elongation factor P 54:125 Synthesis of rhamnosylated arginine glycopeptides and determination of the glycosidic linkage in bacterial elongation factor P. 28451332 3 35 theme 2D 688:689 arg1 NMR 691:693 2D NMR 688:693 2D NMR 688:693 Preparation of a proteolytic fragment of Pseudomonas aeruginosa EF-P bearing both α- and β-rhamnosylated arginine enabled the unequivocal determination of the native glycosidic linkage to be α through 2D NMR and nano-UHPLC-tandem mass spectrometry studies. 28451332 0 36 gly glycopeptides 36:48 arg2 glycopeptides 36:48 rhamnosylated arginine glycopeptides 13:48 rhamnosylated arginine glycopeptides 13:48 Synthesis of rhamnosylated arginine glycopeptides and determination of the glycosidic linkage in bacterial elongation factor P. 28451332 1 37 theme new 130:132 arg1 class 134:138 A new class 128:138 A new class of N-linked protein glycosylation - arginine rhamnosylation - 128:200 A new class of N-linked protein glycosylation - arginine rhamnosylation - has recently been discovered as a critical modification for the function of bacterial elongation factor P (EF-P). 28451332 1 37 theme new 130:132 arg1 modification 245:256 a critical modification 234:256 a critical modification for the function of bacterial elongation factor P (EF-P) 234:313 A new class of N-linked protein glycosylation - arginine rhamnosylation - has recently been discovered as a critical modification for the function of bacterial elongation factor P (EF-P). 28451332 3 38 theme fragment 516:523 arg1 Preparation 487:497 Preparation 487:497 Preparation of a proteolytic fragment of Pseudomonas aeruginosa EF-P bearing both α- and β-rhamnosylated arginine 487:599 Preparation of a proteolytic fragment of Pseudomonas aeruginosa EF-P bearing both α- and β-rhamnosylated arginine enabled the unequivocal determination of the native glycosidic linkage to be α through 2D NMR and nano-UHPLC-tandem mass spectrometry studies. 28451332 3 39 dep aeruginosa 540:549 arg1 EF-P 551:554 EF-P 551:554 Pseudomonas aeruginosa EF-P bearing both α- and β-rhamnosylated arginine 528:599 Preparation of a proteolytic fragment of Pseudomonas aeruginosa EF-P bearing both α- and β-rhamnosylated arginine enabled the unequivocal determination of the native glycosidic linkage to be α through 2D NMR and nano-UHPLC-tandem mass spectrometry studies. 28451332 0 40 theme glycosidic 75:84 arg1 linkage 86:92 the glycosidic linkage 71:92 the glycosidic linkage in bacterial elongation factor P 71:125 Synthesis of rhamnosylated arginine glycopeptides and determination of the glycosidic linkage in bacterial elongation factor P. 28451332 3 41 theme unequivocal 613:623 arg1 determination 625:637 the unequivocal determination 609:637 the unequivocal determination of the native glycosidic linkage 609:670 Preparation of a proteolytic fragment of Pseudomonas aeruginosa EF-P bearing both α- and β-rhamnosylated arginine enabled the unequivocal determination of the native glycosidic linkage to be α through 2D NMR and nano-UHPLC-tandem mass spectrometry studies. 28451332 3 42 theme proteolytic 504:514 arg1 fragment 516:523 a proteolytic fragment 502:523 a proteolytic fragment of Pseudomonas aeruginosa EF-P bearing both α- and β-rhamnosylated arginine 502:599 Preparation of a proteolytic fragment of Pseudomonas aeruginosa EF-P bearing both α- and β-rhamnosylated arginine enabled the unequivocal determination of the native glycosidic linkage to be α through 2D NMR and nano-UHPLC-tandem mass spectrometry studies. 28451332 1 43 theme critical 236:243 arg1 modification 245:256 a critical modification 234:256 a critical modification for the function of bacterial elongation factor P (EF-P) 234:313 A new class of N-linked protein glycosylation - arginine rhamnosylation - has recently been discovered as a critical modification for the function of bacterial elongation factor P (EF-P). 28451332 1 43 theme critical 236:243 arg1 class 134:138 A new class 128:138 A new class of N-linked protein glycosylation - arginine rhamnosylation - 128:200 A new class of N-linked protein glycosylation - arginine rhamnosylation - has recently been discovered as a critical modification for the function of bacterial elongation factor P (EF-P). 28451332 1 44 dep factor 299:304 arg1 EF-P 309:312 EF-P 309:312 EF-P 309:312 A new class of N-linked protein glycosylation - arginine rhamnosylation - has recently been discovered as a critical modification for the function of bacterial elongation factor P (EF-P). 28451332 1 44 dep factor 299:304 arg1 P 306:306 P 306:306 bacterial elongation factor P (EF-P) 278:313 A new class of N-linked protein glycosylation - arginine rhamnosylation - has recently been discovered as a critical modification for the function of bacterial elongation factor P (EF-P). 28451332 2 45 theme cassettes 416:424 arg1 synthesis 340:348 the synthesis 336:348 the synthesis of suitably protected α- and β-rhamnosylated arginine amino acid "cassettes" that can be directly installed into rhamnosylated peptides 336:484 Herein, we describe the synthesis of suitably protected α- and β-rhamnosylated arginine amino acid "cassettes" that can be directly installed into rhamnosylated peptides. 28451332 1 46 theme N-linked 143:150 arg1 glycosylation 160:172 N-linked protein glycosylation 143:172 N-linked protein glycosylation 143:172 A new class of N-linked protein glycosylation - arginine rhamnosylation - has recently been discovered as a critical modification for the function of bacterial elongation factor P (EF-P). 26179435 5 0 theme quality 810:816 arg1 control 818:824 product quality control 802:824 product quality control 802:824 This approach to product quality control ensures a more consistent product for patients, enables greater manufacturing efficiency, and eliminates the need for extensive process characterization by providing direct measures of critical product quality attributes for real time release of drug product. 26179435 3 1 from control 466:472 arg1 process 515:521 a typical biologic process 496:521 a typical biologic process 496:521 The active control of product quality in a typical biologic process is challenging because of measurement lags and nonlinearities present in the system. 26179435 2 2 theme product 373:379 arg1 feature 405:411 an essential feature 392:411 an essential feature of any therapeutic manufacturing process 392:452 The safety and efficacy of a product is crucial, and consistent product quality is an essential feature of any therapeutic manufacturing process. 26179435 2 2 theme product 373:379 arg1 quality 381:387 consistent product quality 362:387 consistent product quality 362:387 The safety and efficacy of a product is crucial, and consistent product quality is an essential feature of any therapeutic manufacturing process. 26179435 0 3 theme glycan 84:89 arg1 levels 91:96 defined N-linked glycan levels 67:96 defined N-linked glycan levels 67:96 Real-time product attribute control to manufacture antibodies with defined N-linked glycan levels. 26179435 5 4 theme extensive 944:952 arg1 characterization 962:977 extensive process characterization 944:977 extensive process characterization 944:977 This approach to product quality control ensures a more consistent product for patients, enables greater manufacturing efficiency, and eliminates the need for extensive process characterization by providing direct measures of critical product quality attributes for real time release of drug product. 26179435 1 5 theme emerging 171:178 arg1 markets 180:186 emerging markets 171:186 emerging markets 171:186 Pressures for cost-effective new therapies and an increased emphasis on emerging markets require technological advancements and a flexible future manufacturing network for the production of biologic medicines. 26179435 2 6 theme consistent 362:371 arg1 feature 405:411 an essential feature 392:411 an essential feature of any therapeutic manufacturing process 392:452 The safety and efficacy of a product is crucial, and consistent product quality is an essential feature of any therapeutic manufacturing process. 26179435 2 6 theme consistent 362:371 arg1 quality 381:387 consistent product quality 362:387 consistent product quality 362:387 The safety and efficacy of a product is crucial, and consistent product quality is an essential feature of any therapeutic manufacturing process. 26179435 5 7 theme quality 1028:1034 arg1 attributes 1036:1045 critical product quality attributes 1011:1045 critical product quality attributes 1011:1045 This approach to product quality control ensures a more consistent product for patients, enables greater manufacturing efficiency, and eliminates the need for extensive process characterization by providing direct measures of critical product quality attributes for real time release of drug product. 26179435 5 8 theme product 1020:1026 arg1 attributes 1036:1045 critical product quality attributes 1011:1045 critical product quality attributes 1011:1045 This approach to product quality control ensures a more consistent product for patients, enables greater manufacturing efficiency, and eliminates the need for extensive process characterization by providing direct measures of critical product quality attributes for real time release of drug product. 26179435 1 9 theme biologic 289:296 arg1 medicines 298:306 biologic medicines 289:306 biologic medicines 289:306 Pressures for cost-effective new therapies and an increased emphasis on emerging markets require technological advancements and a flexible future manufacturing network for the production of biologic medicines. 26179435 5 10 theme attributes 1036:1045 arg1 measures 999:1006 direct measures 992:1006 direct measures of critical product quality attributes 992:1045 This approach to product quality control ensures a more consistent product for patients, enables greater manufacturing efficiency, and eliminates the need for extensive process characterization by providing direct measures of critical product quality attributes for real time release of drug product. 26179435 1 11 theme medicines 298:306 arg1 production 275:284 the production 271:284 the production of biologic medicines 271:306 Pressures for cost-effective new therapies and an increased emphasis on emerging markets require technological advancements and a flexible future manufacturing network for the production of biologic medicines. 26179435 4 12 theme predetermined 720:732 arg1 value 734:738 a predetermined value 718:738 a predetermined value during pilot scale manufacturing operations 718:782 The current study uses nonlinear model predictive control to maintain a critical product quality attribute at a predetermined value during pilot scale manufacturing operations. 26179435 3 13 theme biologic 506:513 arg1 process 515:521 a typical biologic process 496:521 a typical biologic process 496:521 The active control of product quality in a typical biologic process is challenging because of measurement lags and nonlinearities present in the system. 26179435 5 14 theme greater 882:888 arg1 efficiency 904:913 greater manufacturing efficiency 882:913 greater manufacturing efficiency 882:913 This approach to product quality control ensures a more consistent product for patients, enables greater manufacturing efficiency, and eliminates the need for extensive process characterization by providing direct measures of critical product quality attributes for real time release of drug product. 26179435 1 15 from emphasis 159:166 arg1 markets 180:186 emerging markets 171:186 emerging markets 171:186 Pressures for cost-effective new therapies and an increased emphasis on emerging markets require technological advancements and a flexible future manufacturing network for the production of biologic medicines. 26179435 3 16 theme measurement 549:559 arg1 lags 561:564 measurement lags 549:564 measurement lags 549:564 The active control of product quality in a typical biologic process is challenging because of measurement lags and nonlinearities present in the system. 26179435 2 17 theme essential 395:403 arg1 feature 405:411 an essential feature 392:411 an essential feature of any therapeutic manufacturing process 392:452 The safety and efficacy of a product is crucial, and consistent product quality is an essential feature of any therapeutic manufacturing process. 26179435 2 17 theme essential 395:403 arg1 quality 381:387 consistent product quality 362:387 consistent product quality 362:387 The safety and efficacy of a product is crucial, and consistent product quality is an essential feature of any therapeutic manufacturing process. 26179435 3 18 theme active 459:464 arg1 control 466:472 The active control 455:472 The active control of product quality in a typical biologic process 455:521 The active control of product quality in a typical biologic process is challenging because of measurement lags and nonlinearities present in the system. 26179435 4 19 theme current 612:618 arg1 study 620:624 The current study 608:624 The current study 608:624 The current study uses nonlinear model predictive control to maintain a critical product quality attribute at a predetermined value during pilot scale manufacturing operations. 26179435 5 20 theme process 954:960 arg1 characterization 962:977 extensive process characterization 944:977 extensive process characterization 944:977 This approach to product quality control ensures a more consistent product for patients, enables greater manufacturing efficiency, and eliminates the need for extensive process characterization by providing direct measures of critical product quality attributes for real time release of drug product. 26179435 5 21 theme real 1051:1054 arg1 release 1061:1067 real time release 1051:1067 real time release of drug product 1051:1083 This approach to product quality control ensures a more consistent product for patients, enables greater manufacturing efficiency, and eliminates the need for extensive process characterization by providing direct measures of critical product quality attributes for real time release of drug product. 26179435 4 22 theme critical 680:687 arg1 attribute 705:713 a critical product quality attribute 678:713 a critical product quality attribute 678:713 The current study uses nonlinear model predictive control to maintain a critical product quality attribute at a predetermined value during pilot scale manufacturing operations. 26179435 0 23 theme product 10:16 arg1 attribute 18:26 Real-time product attribute 0:26 Real-time product attribute 0:26 Real-time product attribute control to manufacture antibodies with defined N-linked glycan levels. 26179435 2 24 dep safety 313:318 arg1 The 309:311 The 309:311 The 309:311 The safety and efficacy of a product is crucial, and consistent product quality is an essential feature of any therapeutic manufacturing process. 26179435 2 25 theme product 338:344 arg1 safety 313:318 safety 313:318 safety 313:318 The safety and efficacy of a product is crucial, and consistent product quality is an essential feature of any therapeutic manufacturing process. 26179435 2 25 theme product 338:344 arg1 efficacy 324:331 efficacy 324:331 efficacy 324:331 The safety and efficacy of a product is crucial, and consistent product quality is an essential feature of any therapeutic manufacturing process. 26179435 3 26 attach present 585:591 arg2 lags 561:564 measurement lags 549:564 measurement lags 549:564 The active control of product quality in a typical biologic process is challenging because of measurement lags and nonlinearities present in the system. 26179435 3 26 attach present 585:591 arg1 system 600:605 the system 596:605 the system 596:605 The active control of product quality in a typical biologic process is challenging because of measurement lags and nonlinearities present in the system. 26179435 1 27 theme technological 196:208 arg1 advancements 210:221 technological advancements 196:221 technological advancements 196:221 Pressures for cost-effective new therapies and an increased emphasis on emerging markets require technological advancements and a flexible future manufacturing network for the production of biologic medicines. 26179435 0 28 theme Real-time 0:8 arg1 attribute 18:26 Real-time product attribute 0:26 Real-time product attribute 0:26 Real-time product attribute control to manufacture antibodies with defined N-linked glycan levels. 26179435 4 29 theme scale 753:757 arg1 manufacturing 759:771 pilot scale manufacturing 747:771 pilot scale manufacturing operations 747:782 The current study uses nonlinear model predictive control to maintain a critical product quality attribute at a predetermined value during pilot scale manufacturing operations. 26179435 4 30 theme quality 697:703 arg1 attribute 705:713 a critical product quality attribute 678:713 a critical product quality attribute 678:713 The current study uses nonlinear model predictive control to maintain a critical product quality attribute at a predetermined value during pilot scale manufacturing operations. 26179435 5 31 theme manufacturing 890:902 arg1 efficiency 904:913 greater manufacturing efficiency 882:913 greater manufacturing efficiency 882:913 This approach to product quality control ensures a more consistent product for patients, enables greater manufacturing efficiency, and eliminates the need for extensive process characterization by providing direct measures of critical product quality attributes for real time release of drug product. 26179435 5 32 theme direct 992:997 arg1 measures 999:1006 direct measures 992:1006 direct measures of critical product quality attributes 992:1045 This approach to product quality control ensures a more consistent product for patients, enables greater manufacturing efficiency, and eliminates the need for extensive process characterization by providing direct measures of critical product quality attributes for real time release of drug product. 26179435 3 33 theme present 585:591 arg1 lags 561:564 measurement lags 549:564 measurement lags 549:564 The active control of product quality in a typical biologic process is challenging because of measurement lags and nonlinearities present in the system. 26179435 2 34 theme process 446:452 arg1 feature 405:411 an essential feature 392:411 an essential feature of any therapeutic manufacturing process 392:452 The safety and efficacy of a product is crucial, and consistent product quality is an essential feature of any therapeutic manufacturing process. 26179435 2 34 theme process 446:452 arg1 quality 381:387 consistent product quality 362:387 consistent product quality 362:387 The safety and efficacy of a product is crucial, and consistent product quality is an essential feature of any therapeutic manufacturing process. 26179435 3 35 theme quality 485:491 arg1 control 466:472 The active control 455:472 The active control of product quality in a typical biologic process 455:521 The active control of product quality in a typical biologic process is challenging because of measurement lags and nonlinearities present in the system. 26179435 1 36 theme cost-effective 113:126 arg1 therapies 132:140 cost-effective new therapies 113:140 cost-effective new therapies 113:140 Pressures for cost-effective new therapies and an increased emphasis on emerging markets require technological advancements and a flexible future manufacturing network for the production of biologic medicines. 26179435 2 37 theme manufacturing 432:444 arg1 process 446:452 any therapeutic manufacturing process 416:452 any therapeutic manufacturing process 416:452 The safety and efficacy of a product is crucial, and consistent product quality is an essential feature of any therapeutic manufacturing process. 26179435 2 38 theme therapeutic 420:430 arg1 process 446:452 any therapeutic manufacturing process 416:452 any therapeutic manufacturing process 416:452 The safety and efficacy of a product is crucial, and consistent product quality is an essential feature of any therapeutic manufacturing process. 26179435 5 39 theme product 1077:1083 arg1 release 1061:1067 real time release 1051:1067 real time release of drug product 1051:1083 This approach to product quality control ensures a more consistent product for patients, enables greater manufacturing efficiency, and eliminates the need for extensive process characterization by providing direct measures of critical product quality attributes for real time release of drug product. 26179435 3 40 from system 600:605 arg1 present 585:591 present 585:591 present 585:591 The active control of product quality in a typical biologic process is challenging because of measurement lags and nonlinearities present in the system. 26179435 1 41 theme flexible 229:236 arg1 network 259:265 a flexible future manufacturing network 227:265 a flexible future manufacturing network 227:265 Pressures for cost-effective new therapies and an increased emphasis on emerging markets require technological advancements and a flexible future manufacturing network for the production of biologic medicines. 26179435 4 42 theme product 689:695 arg1 attribute 705:713 a critical product quality attribute 678:713 a critical product quality attribute 678:713 The current study uses nonlinear model predictive control to maintain a critical product quality attribute at a predetermined value during pilot scale manufacturing operations. 26179435 1 43 theme future 238:243 arg1 network 259:265 a flexible future manufacturing network 227:265 a flexible future manufacturing network 227:265 Pressures for cost-effective new therapies and an increased emphasis on emerging markets require technological advancements and a flexible future manufacturing network for the production of biologic medicines. 26179435 5 44 theme product 802:808 arg1 control 818:824 product quality control 802:824 product quality control 802:824 This approach to product quality control ensures a more consistent product for patients, enables greater manufacturing efficiency, and eliminates the need for extensive process characterization by providing direct measures of critical product quality attributes for real time release of drug product. 26179435 1 45 theme new 128:130 arg1 therapies 132:140 cost-effective new therapies 113:140 cost-effective new therapies 113:140 Pressures for cost-effective new therapies and an increased emphasis on emerging markets require technological advancements and a flexible future manufacturing network for the production of biologic medicines. 26179435 5 46 theme consistent 841:850 arg1 product 852:858 a more consistent product 834:858 a more consistent product for patients 834:871 This approach to product quality control ensures a more consistent product for patients, enables greater manufacturing efficiency, and eliminates the need for extensive process characterization by providing direct measures of critical product quality attributes for real time release of drug product. 26179435 0 47 link N-linked 75:82 arg1 levels 91:96 defined N-linked glycan levels 67:96 defined N-linked glycan levels 67:96 Real-time product attribute control to manufacture antibodies with defined N-linked glycan levels. 26179435 3 48 from present 585:591 arg1 system 600:605 the system 596:605 the system 596:605 The active control of product quality in a typical biologic process is challenging because of measurement lags and nonlinearities present in the system. 26179435 4 49 theme pilot 747:751 arg1 manufacturing 759:771 pilot scale manufacturing 747:771 pilot scale manufacturing operations 747:782 The current study uses nonlinear model predictive control to maintain a critical product quality attribute at a predetermined value during pilot scale manufacturing operations. 26179435 5 50 theme time 1056:1059 arg1 release 1061:1067 real time release 1051:1067 real time release of drug product 1051:1083 This approach to product quality control ensures a more consistent product for patients, enables greater manufacturing efficiency, and eliminates the need for extensive process characterization by providing direct measures of critical product quality attributes for real time release of drug product. 26179435 4 51 theme manufacturing 759:771 arg1 operations 773:782 pilot scale manufacturing operations 747:782 pilot scale manufacturing operations 747:782 The current study uses nonlinear model predictive control to maintain a critical product quality attribute at a predetermined value during pilot scale manufacturing operations. 26179435 5 52 theme critical 1011:1018 arg1 attributes 1036:1045 critical product quality attributes 1011:1045 critical product quality attributes 1011:1045 This approach to product quality control ensures a more consistent product for patients, enables greater manufacturing efficiency, and eliminates the need for extensive process characterization by providing direct measures of critical product quality attributes for real time release of drug product. 26179435 1 53 theme manufacturing 245:257 arg1 network 259:265 a flexible future manufacturing network 227:265 a flexible future manufacturing network 227:265 Pressures for cost-effective new therapies and an increased emphasis on emerging markets require technological advancements and a flexible future manufacturing network for the production of biologic medicines. 26179435 3 54 theme typical 498:504 arg1 process 515:521 a typical biologic process 496:521 a typical biologic process 496:521 The active control of product quality in a typical biologic process is challenging because of measurement lags and nonlinearities present in the system. 26179435 0 55 theme N-linked 75:82 arg1 levels 91:96 defined N-linked glycan levels 67:96 defined N-linked glycan levels 67:96 Real-time product attribute control to manufacture antibodies with defined N-linked glycan levels. 26179435 3 56 theme product 477:483 arg1 quality 485:491 product quality 477:491 product quality 477:491 The active control of product quality in a typical biologic process is challenging because of measurement lags and nonlinearities present in the system. 26179435 0 57 with antibodies 51:60 arg1 levels 91:96 defined N-linked glycan levels 67:96 defined N-linked glycan levels 67:96 Real-time product attribute control to manufacture antibodies with defined N-linked glycan levels. 26179435 1 58 theme increased 149:157 arg1 emphasis 159:166 an increased emphasis 146:166 an increased emphasis on emerging markets 146:186 Pressures for cost-effective new therapies and an increased emphasis on emerging markets require technological advancements and a flexible future manufacturing network for the production of biologic medicines. 26179435 1 59 from Pressures 99:107 arg1 markets 180:186 emerging markets 171:186 emerging markets 171:186 Pressures for cost-effective new therapies and an increased emphasis on emerging markets require technological advancements and a flexible future manufacturing network for the production of biologic medicines. 26179435 4 60 theme predictive 647:656 arg1 control 658:664 nonlinear model predictive control 631:664 nonlinear model predictive control 631:664 The current study uses nonlinear model predictive control to maintain a critical product quality attribute at a predetermined value during pilot scale manufacturing operations. 26179435 0 61 theme defined 67:73 arg1 levels 91:96 defined N-linked glycan levels 67:96 defined N-linked glycan levels 67:96 Real-time product attribute control to manufacture antibodies with defined N-linked glycan levels. 26179435 5 62 theme drug 1072:1075 arg1 product 1077:1083 drug product 1072:1083 drug product 1072:1083 This approach to product quality control ensures a more consistent product for patients, enables greater manufacturing efficiency, and eliminates the need for extensive process characterization by providing direct measures of critical product quality attributes for real time release of drug product. 26179435 4 63 theme nonlinear 631:639 arg1 control 658:664 nonlinear model predictive control 631:664 nonlinear model predictive control 631:664 The current study uses nonlinear model predictive control to maintain a critical product quality attribute at a predetermined value during pilot scale manufacturing operations. 26179435 4 64 theme model 641:645 arg1 control 658:664 nonlinear model predictive control 631:664 nonlinear model predictive control 631:664 The current study uses nonlinear model predictive control to maintain a critical product quality attribute at a predetermined value during pilot scale manufacturing operations. 25635058 2 0 theme antibody 355:362 arg1 responses 364:372 potent anti-IZ or anti-Fd antibody responses 329:372 potent anti-IZ or anti-Fd antibody responses 329:372 We found that these domains induced potent anti-IZ or anti-Fd antibody responses in animals when fused to an HIV-1 envelope glycoprotein (Env) immunogen. 25635058 1 1 theme foldon 258:263 arg1 domains 284:290 the widely used GCN4-based isoleucine zipper (IZ) and the T4 bacteriophage fibritin foldon (Fd) trimerization domains 174:290 the widely used GCN4-based isoleucine zipper (IZ) and the T4 bacteriophage fibritin foldon (Fd) trimerization domains 174:290 Many therapeutic proteins and protein subunit vaccines contain heterologous trimerization domains, such as the widely used GCN4-based isoleucine zipper (IZ) and the T4 bacteriophage fibritin foldon (Fd) trimerization domains. 25635058 3 2 contain containing 507:516 arg1 domain 500:505 an IZ domain 494:505 an IZ domain containing four N-linked glycans (IZN4) 494:545 To dampen IZ-induced responses, we constructed an IZ domain containing four N-linked glycans (IZN4) to shield the underlying protein surface. 25635058 3 2 contain containing 507:516 arg2 IZN4 541:544 IZN4 541:544 IZN4 541:544 To dampen IZ-induced responses, we constructed an IZ domain containing four N-linked glycans (IZN4) to shield the underlying protein surface. 25635058 3 2 contain containing 507:516 arg2 glycans 532:538 four N-linked glycans 518:538 four N-linked glycans (IZN4) 518:545 To dampen IZ-induced responses, we constructed an IZ domain containing four N-linked glycans (IZN4) to shield the underlying protein surface. 25635058 2 3 gly glycoprotein 417:428 arg1 Env 431:433 Env 431:433 Env 431:433 We found that these domains induced potent anti-IZ or anti-Fd antibody responses in animals when fused to an HIV-1 envelope glycoprotein (Env) immunogen. 25635058 2 3 gly glycoprotein 417:428 arg1 glycoprotein 417:428 HIV-1 envelope glycoprotein 402:428 an HIV-1 envelope glycoprotein (Env) immunogen 399:444 We found that these domains induced potent anti-IZ or anti-Fd antibody responses in animals when fused to an HIV-1 envelope glycoprotein (Env) immunogen. 25635058 2 4 theme anti-Fd 347:353 arg1 responses 364:372 potent anti-IZ or anti-Fd antibody responses 329:372 potent anti-IZ or anti-Fd antibody responses 329:372 We found that these domains induced potent anti-IZ or anti-Fd antibody responses in animals when fused to an HIV-1 envelope glycoprotein (Env) immunogen. 25635058 1 5 theme Many 67:70 arg1 proteins 84:91 Many therapeutic proteins 67:91 Many therapeutic proteins 67:91 Many therapeutic proteins and protein subunit vaccines contain heterologous trimerization domains, such as the widely used GCN4-based isoleucine zipper (IZ) and the T4 bacteriophage fibritin foldon (Fd) trimerization domains. 25635058 4 6 theme antibody 705:712 arg1 responses 714:722 the antibody responses 701:722 the antibody responses against the IZ 701:737 When fused to two different vaccine antigens, HIV-1 Env and influenza hemagglutinin (HA), IZN4 strongly reduced the antibody responses against the IZ, but did not affect the antibody titers against Env or HA. 25635058 3 7 link N-linked 523:530 arg1 glycans 532:538 four N-linked glycans 518:538 four N-linked glycans (IZN4) 518:545 To dampen IZ-induced responses, we constructed an IZ domain containing four N-linked glycans (IZN4) to shield the underlying protein surface. 25635058 3 7 link N-linked 523:530 arg1 IZN4 541:544 IZN4 541:544 IZN4 541:544 To dampen IZ-induced responses, we constructed an IZ domain containing four N-linked glycans (IZN4) to shield the underlying protein surface. 25635058 1 8 theme therapeutic 72:82 arg1 proteins 84:91 Many therapeutic proteins 67:91 Many therapeutic proteins 67:91 Many therapeutic proteins and protein subunit vaccines contain heterologous trimerization domains, such as the widely used GCN4-based isoleucine zipper (IZ) and the T4 bacteriophage fibritin foldon (Fd) trimerization domains. 25635058 3 9 theme IZ-induced 457:466 arg1 responses 468:476 IZ-induced responses 457:476 IZ-induced responses 457:476 To dampen IZ-induced responses, we constructed an IZ domain containing four N-linked glycans (IZN4) to shield the underlying protein surface. 25635058 5 10 theme immunogenic 811:821 arg1 domains 839:845 immunogenic multimerization domains 811:845 immunogenic multimerization domains 811:845 Silencing of immunogenic multimerization domains with glycans might be relevant for therapeutic proteins and protein vaccines. 25635058 1 11 theme used 185:188 arg1 IZ 220:221 IZ 220:221 IZ 220:221 Many therapeutic proteins and protein subunit vaccines contain heterologous trimerization domains, such as the widely used GCN4-based isoleucine zipper (IZ) and the T4 bacteriophage fibritin foldon (Fd) trimerization domains. 25635058 1 11 theme used 185:188 arg1 zipper 212:217 the widely used GCN4-based isoleucine zipper 174:217 the widely used GCN4-based isoleucine zipper (IZ) 174:222 Many therapeutic proteins and protein subunit vaccines contain heterologous trimerization domains, such as the widely used GCN4-based isoleucine zipper (IZ) and the T4 bacteriophage fibritin foldon (Fd) trimerization domains. 25635058 3 12 theme N-linked 523:530 arg1 glycans 532:538 four N-linked glycans 518:538 four N-linked glycans (IZN4) 518:545 To dampen IZ-induced responses, we constructed an IZ domain containing four N-linked glycans (IZN4) to shield the underlying protein surface. 25635058 3 12 theme N-linked 523:530 arg1 IZN4 541:544 IZN4 541:544 IZN4 541:544 To dampen IZ-induced responses, we constructed an IZ domain containing four N-linked glycans (IZN4) to shield the underlying protein surface. 25635058 1 13 theme GCN4-based 190:199 arg1 IZ 220:221 IZ 220:221 IZ 220:221 Many therapeutic proteins and protein subunit vaccines contain heterologous trimerization domains, such as the widely used GCN4-based isoleucine zipper (IZ) and the T4 bacteriophage fibritin foldon (Fd) trimerization domains. 25635058 1 13 theme GCN4-based 190:199 arg1 zipper 212:217 the widely used GCN4-based isoleucine zipper 174:217 the widely used GCN4-based isoleucine zipper (IZ) 174:222 Many therapeutic proteins and protein subunit vaccines contain heterologous trimerization domains, such as the widely used GCN4-based isoleucine zipper (IZ) and the T4 bacteriophage fibritin foldon (Fd) trimerization domains. 25635058 1 14 theme protein 97:103 arg1 vaccines 113:120 protein subunit vaccines 97:120 protein subunit vaccines 97:120 Many therapeutic proteins and protein subunit vaccines contain heterologous trimerization domains, such as the widely used GCN4-based isoleucine zipper (IZ) and the T4 bacteriophage fibritin foldon (Fd) trimerization domains. 25635058 1 15 theme isoleucine 201:210 arg1 IZ 220:221 IZ 220:221 IZ 220:221 Many therapeutic proteins and protein subunit vaccines contain heterologous trimerization domains, such as the widely used GCN4-based isoleucine zipper (IZ) and the T4 bacteriophage fibritin foldon (Fd) trimerization domains. 25635058 1 15 theme isoleucine 201:210 arg1 zipper 212:217 the widely used GCN4-based isoleucine zipper 174:217 the widely used GCN4-based isoleucine zipper (IZ) 174:222 Many therapeutic proteins and protein subunit vaccines contain heterologous trimerization domains, such as the widely used GCN4-based isoleucine zipper (IZ) and the T4 bacteriophage fibritin foldon (Fd) trimerization domains. 25635058 1 16 theme trimerization 270:282 arg1 domains 284:290 the widely used GCN4-based isoleucine zipper (IZ) and the T4 bacteriophage fibritin foldon (Fd) trimerization domains 174:290 the widely used GCN4-based isoleucine zipper (IZ) and the T4 bacteriophage fibritin foldon (Fd) trimerization domains 174:290 Many therapeutic proteins and protein subunit vaccines contain heterologous trimerization domains, such as the widely used GCN4-based isoleucine zipper (IZ) and the T4 bacteriophage fibritin foldon (Fd) trimerization domains. 25635058 4 17 theme HIV-1 635:639 arg1 Env 641:643 HIV-1 Env 635:643 HIV-1 Env 635:643 When fused to two different vaccine antigens, HIV-1 Env and influenza hemagglutinin (HA), IZN4 strongly reduced the antibody responses against the IZ, but did not affect the antibody titers against Env or HA. 25635058 1 18 theme subunit 105:111 arg1 vaccines 113:120 protein subunit vaccines 97:120 protein subunit vaccines 97:120 Many therapeutic proteins and protein subunit vaccines contain heterologous trimerization domains, such as the widely used GCN4-based isoleucine zipper (IZ) and the T4 bacteriophage fibritin foldon (Fd) trimerization domains. 25635058 1 19 theme zipper 212:217 arg1 domains 284:290 the widely used GCN4-based isoleucine zipper (IZ) and the T4 bacteriophage fibritin foldon (Fd) trimerization domains 174:290 the widely used GCN4-based isoleucine zipper (IZ) and the T4 bacteriophage fibritin foldon (Fd) trimerization domains 174:290 Many therapeutic proteins and protein subunit vaccines contain heterologous trimerization domains, such as the widely used GCN4-based isoleucine zipper (IZ) and the T4 bacteriophage fibritin foldon (Fd) trimerization domains. 25635058 0 20 theme immunogenic 25:35 arg1 domain 59:64 a highly immunogenic protein trimerization domain 16:64 a highly immunogenic protein trimerization domain 16:64 Immunosilencing a highly immunogenic protein trimerization domain. 25635058 1 21 dep such 166:169 arg1 as 171:172 as 171:172 as 171:172 Many therapeutic proteins and protein subunit vaccines contain heterologous trimerization domains, such as the widely used GCN4-based isoleucine zipper (IZ) and the T4 bacteriophage fibritin foldon (Fd) trimerization domains. 25635058 4 22 theme antibody 763:770 arg1 titers 772:777 the antibody titers 759:777 the antibody titers against Env or HA 759:795 When fused to two different vaccine antigens, HIV-1 Env and influenza hemagglutinin (HA), IZN4 strongly reduced the antibody responses against the IZ, but did not affect the antibody titers against Env or HA. 25635058 2 23 theme glycoprotein 417:428 arg1 immunogen 436:444 an HIV-1 envelope glycoprotein (Env) immunogen 399:444 an HIV-1 envelope glycoprotein (Env) immunogen 399:444 We found that these domains induced potent anti-IZ or anti-Fd antibody responses in animals when fused to an HIV-1 envelope glycoprotein (Env) immunogen. 25635058 3 24 theme IZ 497:498 arg1 domain 500:505 an IZ domain 494:505 an IZ domain containing four N-linked glycans (IZN4) 494:545 To dampen IZ-induced responses, we constructed an IZ domain containing four N-linked glycans (IZN4) to shield the underlying protein surface. 25635058 2 25 theme envelope 408:415 arg1 Env 431:433 Env 431:433 Env 431:433 We found that these domains induced potent anti-IZ or anti-Fd antibody responses in animals when fused to an HIV-1 envelope glycoprotein (Env) immunogen. 25635058 2 25 theme envelope 408:415 arg1 glycoprotein 417:428 HIV-1 envelope glycoprotein 402:428 an HIV-1 envelope glycoprotein (Env) immunogen 399:444 We found that these domains induced potent anti-IZ or anti-Fd antibody responses in animals when fused to an HIV-1 envelope glycoprotein (Env) immunogen. 25635058 0 26 theme trimerization 45:57 arg1 domain 59:64 a highly immunogenic protein trimerization domain 16:64 a highly immunogenic protein trimerization domain 16:64 Immunosilencing a highly immunogenic protein trimerization domain. 25635058 2 27 theme anti-IZ 336:342 arg1 responses 364:372 potent anti-IZ or anti-Fd antibody responses 329:372 potent anti-IZ or anti-Fd antibody responses 329:372 We found that these domains induced potent anti-IZ or anti-Fd antibody responses in animals when fused to an HIV-1 envelope glycoprotein (Env) immunogen. 25635058 3 28 theme protein 572:578 arg1 surface 580:586 the underlying protein surface 557:586 the underlying protein surface 557:586 To dampen IZ-induced responses, we constructed an IZ domain containing four N-linked glycans (IZN4) to shield the underlying protein surface. 25635058 5 29 theme multimerization 823:837 arg1 domains 839:845 immunogenic multimerization domains 811:845 immunogenic multimerization domains 811:845 Silencing of immunogenic multimerization domains with glycans might be relevant for therapeutic proteins and protein vaccines. 25635058 2 30 theme HIV-1 402:406 arg1 Env 431:433 Env 431:433 Env 431:433 We found that these domains induced potent anti-IZ or anti-Fd antibody responses in animals when fused to an HIV-1 envelope glycoprotein (Env) immunogen. 25635058 2 30 theme HIV-1 402:406 arg1 glycoprotein 417:428 HIV-1 envelope glycoprotein 402:428 an HIV-1 envelope glycoprotein (Env) immunogen 399:444 We found that these domains induced potent anti-IZ or anti-Fd antibody responses in animals when fused to an HIV-1 envelope glycoprotein (Env) immunogen. 25635058 0 31 theme protein 37:43 arg1 domain 59:64 a highly immunogenic protein trimerization domain 16:64 a highly immunogenic protein trimerization domain 16:64 Immunosilencing a highly immunogenic protein trimerization domain. 25635058 1 32 contain contain 122:128 arg1 proteins 84:91 Many therapeutic proteins 67:91 Many therapeutic proteins 67:91 Many therapeutic proteins and protein subunit vaccines contain heterologous trimerization domains, such as the widely used GCN4-based isoleucine zipper (IZ) and the T4 bacteriophage fibritin foldon (Fd) trimerization domains. 25635058 1 32 contain contain 122:128 arg1 vaccines 113:120 protein subunit vaccines 97:120 protein subunit vaccines 97:120 Many therapeutic proteins and protein subunit vaccines contain heterologous trimerization domains, such as the widely used GCN4-based isoleucine zipper (IZ) and the T4 bacteriophage fibritin foldon (Fd) trimerization domains. 25635058 1 32 contain contain 122:128 arg2 domains 284:290 the widely used GCN4-based isoleucine zipper (IZ) and the T4 bacteriophage fibritin foldon (Fd) trimerization domains 174:290 the widely used GCN4-based isoleucine zipper (IZ) and the T4 bacteriophage fibritin foldon (Fd) trimerization domains 174:290 Many therapeutic proteins and protein subunit vaccines contain heterologous trimerization domains, such as the widely used GCN4-based isoleucine zipper (IZ) and the T4 bacteriophage fibritin foldon (Fd) trimerization domains. 25635058 1 32 contain contain 122:128 arg2 domains 157:163 heterologous trimerization domains 130:163 heterologous trimerization domains 130:163 Many therapeutic proteins and protein subunit vaccines contain heterologous trimerization domains, such as the widely used GCN4-based isoleucine zipper (IZ) and the T4 bacteriophage fibritin foldon (Fd) trimerization domains. 25635058 4 33 theme vaccine 617:623 arg1 antigens 625:632 two different vaccine antigens 603:632 two different vaccine antigens 603:632 When fused to two different vaccine antigens, HIV-1 Env and influenza hemagglutinin (HA), IZN4 strongly reduced the antibody responses against the IZ, but did not affect the antibody titers against Env or HA. 25635058 1 34 theme heterologous 130:141 arg1 domains 157:163 heterologous trimerization domains 130:163 heterologous trimerization domains 130:163 Many therapeutic proteins and protein subunit vaccines contain heterologous trimerization domains, such as the widely used GCN4-based isoleucine zipper (IZ) and the T4 bacteriophage fibritin foldon (Fd) trimerization domains. 25635058 3 35 theme underlying 561:570 arg1 surface 580:586 the underlying protein surface 557:586 the underlying protein surface 557:586 To dampen IZ-induced responses, we constructed an IZ domain containing four N-linked glycans (IZN4) to shield the underlying protein surface. 25635058 1 36 theme trimerization 143:155 arg1 domains 157:163 heterologous trimerization domains 130:163 heterologous trimerization domains 130:163 Many therapeutic proteins and protein subunit vaccines contain heterologous trimerization domains, such as the widely used GCN4-based isoleucine zipper (IZ) and the T4 bacteriophage fibritin foldon (Fd) trimerization domains. 25635058 5 37 with Silencing 798:806 arg1 glycans 852:858 glycans 852:858 glycans 852:858 Silencing of immunogenic multimerization domains with glycans might be relevant for therapeutic proteins and protein vaccines. 25635058 2 38 theme potent 329:334 arg1 responses 364:372 potent anti-IZ or anti-Fd antibody responses 329:372 potent anti-IZ or anti-Fd antibody responses 329:372 We found that these domains induced potent anti-IZ or anti-Fd antibody responses in animals when fused to an HIV-1 envelope glycoprotein (Env) immunogen. 25635058 5 39 theme protein 907:913 arg1 vaccines 915:922 protein vaccines 907:922 protein vaccines 907:922 Silencing of immunogenic multimerization domains with glycans might be relevant for therapeutic proteins and protein vaccines. 25635058 5 40 theme therapeutic 882:892 arg1 proteins 894:901 therapeutic proteins 882:901 therapeutic proteins 882:901 Silencing of immunogenic multimerization domains with glycans might be relevant for therapeutic proteins and protein vaccines. 25635058 1 41 theme T4 232:233 arg1 Fd 266:267 Fd 266:267 Fd 266:267 Many therapeutic proteins and protein subunit vaccines contain heterologous trimerization domains, such as the widely used GCN4-based isoleucine zipper (IZ) and the T4 bacteriophage fibritin foldon (Fd) trimerization domains. 25635058 1 41 theme T4 232:233 arg1 foldon 258:263 the T4 bacteriophage fibritin foldon 228:263 the T4 bacteriophage fibritin foldon (Fd) 228:268 Many therapeutic proteins and protein subunit vaccines contain heterologous trimerization domains, such as the widely used GCN4-based isoleucine zipper (IZ) and the T4 bacteriophage fibritin foldon (Fd) trimerization domains. 25635058 4 42 theme different 607:615 arg1 antigens 625:632 two different vaccine antigens 603:632 two different vaccine antigens 603:632 When fused to two different vaccine antigens, HIV-1 Env and influenza hemagglutinin (HA), IZN4 strongly reduced the antibody responses against the IZ, but did not affect the antibody titers against Env or HA. 25635058 5 43 theme domains 839:845 arg1 Silencing 798:806 Silencing 798:806 Silencing of immunogenic multimerization domains with glycans 798:858 Silencing of immunogenic multimerization domains with glycans might be relevant for therapeutic proteins and protein vaccines. 25635058 1 44 theme bacteriophage 235:247 arg1 Fd 266:267 Fd 266:267 Fd 266:267 Many therapeutic proteins and protein subunit vaccines contain heterologous trimerization domains, such as the widely used GCN4-based isoleucine zipper (IZ) and the T4 bacteriophage fibritin foldon (Fd) trimerization domains. 25635058 1 44 theme bacteriophage 235:247 arg1 foldon 258:263 the T4 bacteriophage fibritin foldon 228:263 the T4 bacteriophage fibritin foldon (Fd) 228:268 Many therapeutic proteins and protein subunit vaccines contain heterologous trimerization domains, such as the widely used GCN4-based isoleucine zipper (IZ) and the T4 bacteriophage fibritin foldon (Fd) trimerization domains. 25635058 4 45 theme influenza 649:657 arg1 HA 674:675 HA 674:675 HA 674:675 When fused to two different vaccine antigens, HIV-1 Env and influenza hemagglutinin (HA), IZN4 strongly reduced the antibody responses against the IZ, but did not affect the antibody titers against Env or HA. 25635058 4 45 theme influenza 649:657 arg1 hemagglutinin 659:671 influenza hemagglutinin 649:671 influenza hemagglutinin (HA) 649:676 When fused to two different vaccine antigens, HIV-1 Env and influenza hemagglutinin (HA), IZN4 strongly reduced the antibody responses against the IZ, but did not affect the antibody titers against Env or HA. 25635058 1 46 theme fibritin 249:256 arg1 Fd 266:267 Fd 266:267 Fd 266:267 Many therapeutic proteins and protein subunit vaccines contain heterologous trimerization domains, such as the widely used GCN4-based isoleucine zipper (IZ) and the T4 bacteriophage fibritin foldon (Fd) trimerization domains. 25635058 1 46 theme fibritin 249:256 arg1 foldon 258:263 the T4 bacteriophage fibritin foldon 228:263 the T4 bacteriophage fibritin foldon (Fd) 228:268 Many therapeutic proteins and protein subunit vaccines contain heterologous trimerization domains, such as the widely used GCN4-based isoleucine zipper (IZ) and the T4 bacteriophage fibritin foldon (Fd) trimerization domains. 29069815 3 0 from regulator 379:387 arg1 cells 425:429 cancer cells 418:429 cancer cells 418:429 Herein, we reveal that downregulation of RPN2, which may be a crucial regulator of N-linked glycosylation in cancer cells and drug-resistant cancer cells, promoted the progression of colorectal cancer (CRC) cell cycle and proliferation in vitro and in vivo. 29069815 3 0 from regulator 379:387 arg1 cells 457:461 drug-resistant cancer cells 435:461 drug-resistant cancer cells 435:461 Herein, we reveal that downregulation of RPN2, which may be a crucial regulator of N-linked glycosylation in cancer cells and drug-resistant cancer cells, promoted the progression of colorectal cancer (CRC) cell cycle and proliferation in vitro and in vivo. 29069815 4 1 theme surface 661:667 arg1 EGFR 621:624 EGFR 621:624 EGFR 621:624 We found that RPN2 silencing reduced glycosylation of EGFR, a highly N-link glycosylated cell surface glycoprotein that plays a critical role in majority of human cancers correlating with increased cell growth, proliferation, and differentiation. 29069815 4 1 theme surface 661:667 arg1 glycoprotein 669:680 a highly N-link glycosylated cell surface glycoprotein 627:680 a highly N-link glycosylated cell surface glycoprotein that plays a critical role in majority of human cancers correlating with increased cell growth, proliferation, and differentiation 627:811 We found that RPN2 silencing reduced glycosylation of EGFR, a highly N-link glycosylated cell surface glycoprotein that plays a critical role in majority of human cancers correlating with increased cell growth, proliferation, and differentiation. 29069815 6 2 theme CRC 973:975 arg1 proliferation 982:994 CRC cell proliferation 973:994 CRC cell proliferation 973:994 In summary, our findings suggest that RPN2 regulates CRC cell proliferation through mediating the glycosylation of EGFR which affecting the EGFR/ERK signaling pathways. 29069815 6 3 theme EGFR 1035:1038 arg1 glycosylation 1018:1030 the glycosylation 1014:1030 the glycosylation of EGFR which affecting the EGFR/ERK signaling pathways 1014:1086 In summary, our findings suggest that RPN2 regulates CRC cell proliferation through mediating the glycosylation of EGFR which affecting the EGFR/ERK signaling pathways. 29069815 3 4 theme colorectal 492:501 arg1 CRC 511:513 CRC 511:513 CRC 511:513 Herein, we reveal that downregulation of RPN2, which may be a crucial regulator of N-linked glycosylation in cancer cells and drug-resistant cancer cells, promoted the progression of colorectal cancer (CRC) cell cycle and proliferation in vitro and in vivo. 29069815 3 4 theme colorectal 492:501 arg1 cancer 503:508 colorectal cancer 492:508 colorectal cancer (CRC) cell cycle 492:525 Herein, we reveal that downregulation of RPN2, which may be a crucial regulator of N-linked glycosylation in cancer cells and drug-resistant cancer cells, promoted the progression of colorectal cancer (CRC) cell cycle and proliferation in vitro and in vivo. 29069815 3 5 theme RPN2 350:353 arg1 downregulation 332:345 downregulation 332:345 downregulation of RPN2, which may be a crucial regulator of N-linked glycosylation in cancer cells and drug-resistant cancer cells, 332:462 Herein, we reveal that downregulation of RPN2, which may be a crucial regulator of N-linked glycosylation in cancer cells and drug-resistant cancer cells, promoted the progression of colorectal cancer (CRC) cell cycle and proliferation in vitro and in vivo. 29069815 4 6 theme glycosylated 643:654 arg1 EGFR 621:624 EGFR 621:624 EGFR 621:624 We found that RPN2 silencing reduced glycosylation of EGFR, a highly N-link glycosylated cell surface glycoprotein that plays a critical role in majority of human cancers correlating with increased cell growth, proliferation, and differentiation. 29069815 4 6 theme glycosylated 643:654 arg1 glycoprotein 669:680 a highly N-link glycosylated cell surface glycoprotein 627:680 a highly N-link glycosylated cell surface glycoprotein that plays a critical role in majority of human cancers correlating with increased cell growth, proliferation, and differentiation 627:811 We found that RPN2 silencing reduced glycosylation of EGFR, a highly N-link glycosylated cell surface glycoprotein that plays a critical role in majority of human cancers correlating with increased cell growth, proliferation, and differentiation. 29069815 3 7 theme cell 516:519 arg1 cycle 521:525 colorectal cancer (CRC) cell cycle 492:525 colorectal cancer (CRC) cell cycle 492:525 Herein, we reveal that downregulation of RPN2, which may be a crucial regulator of N-linked glycosylation in cancer cells and drug-resistant cancer cells, promoted the progression of colorectal cancer (CRC) cell cycle and proliferation in vitro and in vivo. 29069815 3 8 theme cycle 521:525 arg1 progression 477:487 the progression 473:487 the progression of colorectal cancer (CRC) cell cycle and proliferation 473:543 Herein, we reveal that downregulation of RPN2, which may be a crucial regulator of N-linked glycosylation in cancer cells and drug-resistant cancer cells, promoted the progression of colorectal cancer (CRC) cell cycle and proliferation in vitro and in vivo. 29069815 0 9 theme EGFR 98:101 arg1 status 88:93 the glycosylation status 70:93 the glycosylation status of EGFR 70:101 RPN2 promotes colorectal cancer cell proliferation through modulating the glycosylation status of EGFR. 29069815 0 10 gly glycosylation 74:86 arg1 EGFR 98:101 EGFR 98:101 EGFR 98:101 RPN2 promotes colorectal cancer cell proliferation through modulating the glycosylation status of EGFR. 29069815 2 11 theme cell 273:276 arg1 proliferation 278:290 cancer cell proliferation 266:290 cancer cell proliferation 266:290 However, the underlying mechanism by which RPN2 regulates cancer cell proliferation remains unclear. 29069815 5 12 theme EGFR 898:901 arg1 deglycosylation 903:917 EGFR deglycosylation 898:917 EGFR deglycosylation 898:917 In addition, RPN2 knockdown decreased EGFR expression and cell surface transport by EGFR deglycosylation. 29069815 4 13 theme cell 656:659 arg1 EGFR 621:624 EGFR 621:624 EGFR 621:624 We found that RPN2 silencing reduced glycosylation of EGFR, a highly N-link glycosylated cell surface glycoprotein that plays a critical role in majority of human cancers correlating with increased cell growth, proliferation, and differentiation. 29069815 4 13 theme cell 656:659 arg1 glycoprotein 669:680 a highly N-link glycosylated cell surface glycoprotein 627:680 a highly N-link glycosylated cell surface glycoprotein that plays a critical role in majority of human cancers correlating with increased cell growth, proliferation, and differentiation 627:811 We found that RPN2 silencing reduced glycosylation of EGFR, a highly N-link glycosylated cell surface glycoprotein that plays a critical role in majority of human cancers correlating with increased cell growth, proliferation, and differentiation. 29069815 6 14 theme EGFR/ERK 1060:1067 arg1 pathways 1079:1086 the EGFR/ERK signaling pathways 1056:1086 the EGFR/ERK signaling pathways 1056:1086 In summary, our findings suggest that RPN2 regulates CRC cell proliferation through mediating the glycosylation of EGFR which affecting the EGFR/ERK signaling pathways. 29069815 2 15 theme cancer 266:271 arg1 proliferation 278:290 cancer cell proliferation 266:290 cancer cell proliferation 266:290 However, the underlying mechanism by which RPN2 regulates cancer cell proliferation remains unclear. 29069815 1 16 theme cell 176:179 arg1 growth 181:186 cell growth 176:186 cell growth in several cancers 176:205 Various studies have found that silencing ribophorin II (RPN2) inhibits cell growth in several cancers. 29069815 3 17 theme cancer 418:423 arg1 cells 425:429 cancer cells 418:429 cancer cells 418:429 Herein, we reveal that downregulation of RPN2, which may be a crucial regulator of N-linked glycosylation in cancer cells and drug-resistant cancer cells, promoted the progression of colorectal cancer (CRC) cell cycle and proliferation in vitro and in vivo. 29069815 7 18 theme colorectal 1197:1206 arg1 size 1214:1217 colorectal tumor size 1197:1217 colorectal tumor size 1197:1217 Clinicopathological analysis showed that the overexpression of RPN2 and EGFR was positively correlated with colorectal tumor size. 29069815 5 19 theme cell 872:875 arg1 transport 885:893 cell surface transport 872:893 cell surface transport 872:893 In addition, RPN2 knockdown decreased EGFR expression and cell surface transport by EGFR deglycosylation. 29069815 7 20 theme RPN2 1152:1155 arg1 overexpression 1134:1147 the overexpression 1130:1147 the overexpression of RPN2 and EGFR 1130:1164 Clinicopathological analysis showed that the overexpression of RPN2 and EGFR was positively correlated with colorectal tumor size. 29069815 4 21 theme cancers 730:736 arg1 majority 712:719 majority 712:719 majority of human cancers correlating with increased cell growth, proliferation, and differentiation 712:811 We found that RPN2 silencing reduced glycosylation of EGFR, a highly N-link glycosylated cell surface glycoprotein that plays a critical role in majority of human cancers correlating with increased cell growth, proliferation, and differentiation. 29069815 6 22 theme signaling 1069:1077 arg1 pathways 1079:1086 the EGFR/ERK signaling pathways 1056:1086 the EGFR/ERK signaling pathways 1056:1086 In summary, our findings suggest that RPN2 regulates CRC cell proliferation through mediating the glycosylation of EGFR which affecting the EGFR/ERK signaling pathways. 29069815 4 23 theme EGFR 621:624 arg1 glycosylation 604:616 glycosylation 604:616 glycosylation of EGFR, a highly N-link glycosylated cell surface glycoprotein that plays a critical role in majority of human cancers correlating with increased cell growth, proliferation, and differentiation 604:811 We found that RPN2 silencing reduced glycosylation of EGFR, a highly N-link glycosylated cell surface glycoprotein that plays a critical role in majority of human cancers correlating with increased cell growth, proliferation, and differentiation. 29069815 4 24 gly glycosylation 604:616 arg1 glycoprotein 669:680 a highly N-link glycosylated cell surface glycoprotein 627:680 a highly N-link glycosylated cell surface glycoprotein that plays a critical role in majority of human cancers correlating with increased cell growth, proliferation, and differentiation 627:811 We found that RPN2 silencing reduced glycosylation of EGFR, a highly N-link glycosylated cell surface glycoprotein that plays a critical role in majority of human cancers correlating with increased cell growth, proliferation, and differentiation. 29069815 4 24 gly glycosylation 604:616 arg1 EGFR 621:624 EGFR 621:624 EGFR 621:624 We found that RPN2 silencing reduced glycosylation of EGFR, a highly N-link glycosylated cell surface glycoprotein that plays a critical role in majority of human cancers correlating with increased cell growth, proliferation, and differentiation. 29069815 3 25 theme glycosylation 401:413 arg1 regulator 379:387 a crucial regulator 369:387 a crucial regulator of N-linked glycosylation in cancer cells and drug-resistant cancer cells 369:461 Herein, we reveal that downregulation of RPN2, which may be a crucial regulator of N-linked glycosylation in cancer cells and drug-resistant cancer cells, promoted the progression of colorectal cancer (CRC) cell cycle and proliferation in vitro and in vivo. 29069815 3 25 theme glycosylation 401:413 arg1 RPN2 350:353 RPN2 350:353 RPN2 350:353 Herein, we reveal that downregulation of RPN2, which may be a crucial regulator of N-linked glycosylation in cancer cells and drug-resistant cancer cells, promoted the progression of colorectal cancer (CRC) cell cycle and proliferation in vitro and in vivo. 29069815 4 26 theme critical 695:702 arg1 role 704:707 a critical role 693:707 a critical role 693:707 We found that RPN2 silencing reduced glycosylation of EGFR, a highly N-link glycosylated cell surface glycoprotein that plays a critical role in majority of human cancers correlating with increased cell growth, proliferation, and differentiation. 29069815 8 27 theme therapeutic 1249:1259 arg1 target 1261:1266 a new therapeutic target 1243:1266 a new therapeutic target 1243:1266 Therefore, RPN2 may be a new therapeutic target and prognostic biomarker for CRC. 29069815 8 27 theme therapeutic 1249:1259 arg1 RPN2 1231:1234 RPN2 1231:1234 RPN2 1231:1234 Therefore, RPN2 may be a new therapeutic target and prognostic biomarker for CRC. 29069815 0 28 theme cancer 25:30 arg1 proliferation 37:49 colorectal cancer cell proliferation 14:49 colorectal cancer cell proliferation 14:49 RPN2 promotes colorectal cancer cell proliferation through modulating the glycosylation status of EGFR. 29069815 4 29 gly glycoprotein 669:680 arg1 EGFR 621:624 EGFR 621:624 EGFR 621:624 We found that RPN2 silencing reduced glycosylation of EGFR, a highly N-link glycosylated cell surface glycoprotein that plays a critical role in majority of human cancers correlating with increased cell growth, proliferation, and differentiation. 29069815 4 29 gly glycoprotein 669:680 arg1 glycoprotein 669:680 a highly N-link glycosylated cell surface glycoprotein 627:680 a highly N-link glycosylated cell surface glycoprotein that plays a critical role in majority of human cancers correlating with increased cell growth, proliferation, and differentiation 627:811 We found that RPN2 silencing reduced glycosylation of EGFR, a highly N-link glycosylated cell surface glycoprotein that plays a critical role in majority of human cancers correlating with increased cell growth, proliferation, and differentiation. 29069815 1 30 theme Various 104:110 arg1 studies 112:118 Various studies 104:118 Various studies 104:118 Various studies have found that silencing ribophorin II (RPN2) inhibits cell growth in several cancers. 29069815 7 31 theme Clinicopathological 1089:1107 arg1 analysis 1109:1116 Clinicopathological analysis 1089:1116 Clinicopathological analysis 1089:1116 Clinicopathological analysis showed that the overexpression of RPN2 and EGFR was positively correlated with colorectal tumor size. 29069815 3 32 theme cancer 450:455 arg1 cells 457:461 drug-resistant cancer cells 435:461 drug-resistant cancer cells 435:461 Herein, we reveal that downregulation of RPN2, which may be a crucial regulator of N-linked glycosylation in cancer cells and drug-resistant cancer cells, promoted the progression of colorectal cancer (CRC) cell cycle and proliferation in vitro and in vivo. 29069815 0 33 theme colorectal 14:23 arg1 proliferation 37:49 colorectal cancer cell proliferation 14:49 colorectal cancer cell proliferation 14:49 RPN2 promotes colorectal cancer cell proliferation through modulating the glycosylation status of EGFR. 29069815 4 34 dep glycosylated 643:654 arg1 N-link 636:641 N-link 636:641 N-link 636:641 We found that RPN2 silencing reduced glycosylation of EGFR, a highly N-link glycosylated cell surface glycoprotein that plays a critical role in majority of human cancers correlating with increased cell growth, proliferation, and differentiation. 29069815 3 35 theme proliferation 531:543 arg1 progression 477:487 the progression 473:487 the progression of colorectal cancer (CRC) cell cycle and proliferation 473:543 Herein, we reveal that downregulation of RPN2, which may be a crucial regulator of N-linked glycosylation in cancer cells and drug-resistant cancer cells, promoted the progression of colorectal cancer (CRC) cell cycle and proliferation in vitro and in vivo. 29069815 1 36 theme several 191:197 arg1 cancers 199:205 several cancers 191:205 several cancers 191:205 Various studies have found that silencing ribophorin II (RPN2) inhibits cell growth in several cancers. 29069815 7 37 theme tumor 1208:1212 arg1 size 1214:1217 colorectal tumor size 1197:1217 colorectal tumor size 1197:1217 Clinicopathological analysis showed that the overexpression of RPN2 and EGFR was positively correlated with colorectal tumor size. 29069815 2 38 theme underlying 221:230 arg1 mechanism 232:240 the underlying mechanism 217:240 the underlying mechanism by which RPN2 regulates cancer cell proliferation 217:290 However, the underlying mechanism by which RPN2 regulates cancer cell proliferation remains unclear. 29069815 8 39 theme prognostic 1272:1281 arg1 biomarker 1283:1291 prognostic biomarker 1272:1291 prognostic biomarker 1272:1291 Therefore, RPN2 may be a new therapeutic target and prognostic biomarker for CRC. 29069815 0 40 theme cell 32:35 arg1 proliferation 37:49 colorectal cancer cell proliferation 14:49 colorectal cancer cell proliferation 14:49 RPN2 promotes colorectal cancer cell proliferation through modulating the glycosylation status of EGFR. 29069815 3 41 theme N-linked 392:399 arg1 glycosylation 401:413 N-linked glycosylation 392:413 N-linked glycosylation 392:413 Herein, we reveal that downregulation of RPN2, which may be a crucial regulator of N-linked glycosylation in cancer cells and drug-resistant cancer cells, promoted the progression of colorectal cancer (CRC) cell cycle and proliferation in vitro and in vivo. 29069815 7 42 theme EGFR 1161:1164 arg1 overexpression 1134:1147 the overexpression 1130:1147 the overexpression of RPN2 and EGFR 1130:1164 Clinicopathological analysis showed that the overexpression of RPN2 and EGFR was positively correlated with colorectal tumor size. 29069815 3 43 theme drug-resistant 435:448 arg1 cells 457:461 drug-resistant cancer cells 435:461 drug-resistant cancer cells 435:461 Herein, we reveal that downregulation of RPN2, which may be a crucial regulator of N-linked glycosylation in cancer cells and drug-resistant cancer cells, promoted the progression of colorectal cancer (CRC) cell cycle and proliferation in vitro and in vivo. 29069815 3 44 theme crucial 371:377 arg1 regulator 379:387 a crucial regulator 369:387 a crucial regulator of N-linked glycosylation in cancer cells and drug-resistant cancer cells 369:461 Herein, we reveal that downregulation of RPN2, which may be a crucial regulator of N-linked glycosylation in cancer cells and drug-resistant cancer cells, promoted the progression of colorectal cancer (CRC) cell cycle and proliferation in vitro and in vivo. 29069815 3 44 theme crucial 371:377 arg1 RPN2 350:353 RPN2 350:353 RPN2 350:353 Herein, we reveal that downregulation of RPN2, which may be a crucial regulator of N-linked glycosylation in cancer cells and drug-resistant cancer cells, promoted the progression of colorectal cancer (CRC) cell cycle and proliferation in vitro and in vivo. 29069815 5 45 theme EGFR 852:855 arg1 expression 857:866 EGFR expression 852:866 EGFR expression 852:866 In addition, RPN2 knockdown decreased EGFR expression and cell surface transport by EGFR deglycosylation. 29069815 5 46 theme surface 877:883 arg1 transport 885:893 cell surface transport 872:893 cell surface transport 872:893 In addition, RPN2 knockdown decreased EGFR expression and cell surface transport by EGFR deglycosylation. 29069815 6 47 gly glycosylation 1018:1030 arg1 signaling 1069:1077 the EGFR/ERK signaling pathways 1056:1086 the EGFR/ERK signaling pathways 1056:1086 In summary, our findings suggest that RPN2 regulates CRC cell proliferation through mediating the glycosylation of EGFR which affecting the EGFR/ERK signaling pathways. 29069815 6 47 gly glycosylation 1018:1030 arg1 EGFR 1035:1038 EGFR 1035:1038 EGFR 1035:1038 In summary, our findings suggest that RPN2 regulates CRC cell proliferation through mediating the glycosylation of EGFR which affecting the EGFR/ERK signaling pathways. 29069815 6 47 gly glycosylation 1018:1030 arg1 EGFR/ERK 1060:1067 the EGFR/ERK signaling pathways 1056:1086 the EGFR/ERK signaling pathways 1056:1086 In summary, our findings suggest that RPN2 regulates CRC cell proliferation through mediating the glycosylation of EGFR which affecting the EGFR/ERK signaling pathways. 29069815 4 48 gly glycosylated 643:654 arg1 EGFR 621:624 EGFR 621:624 EGFR 621:624 We found that RPN2 silencing reduced glycosylation of EGFR, a highly N-link glycosylated cell surface glycoprotein that plays a critical role in majority of human cancers correlating with increased cell growth, proliferation, and differentiation. 29069815 4 48 gly glycosylated 643:654 arg1 glycoprotein 669:680 a highly N-link glycosylated cell surface glycoprotein 627:680 a highly N-link glycosylated cell surface glycoprotein that plays a critical role in majority of human cancers correlating with increased cell growth, proliferation, and differentiation 627:811 We found that RPN2 silencing reduced glycosylation of EGFR, a highly N-link glycosylated cell surface glycoprotein that plays a critical role in majority of human cancers correlating with increased cell growth, proliferation, and differentiation. 29069815 3 49 link N-linked 392:399 arg1 glycosylation 401:413 N-linked glycosylation 392:413 N-linked glycosylation 392:413 Herein, we reveal that downregulation of RPN2, which may be a crucial regulator of N-linked glycosylation in cancer cells and drug-resistant cancer cells, promoted the progression of colorectal cancer (CRC) cell cycle and proliferation in vitro and in vivo. 29069815 1 50 theme ribophorin 146:155 arg1 II 157:158 silencing ribophorin II 136:158 silencing ribophorin II (RPN2) 136:165 Various studies have found that silencing ribophorin II (RPN2) inhibits cell growth in several cancers. 29069815 1 50 theme ribophorin 146:155 arg1 RPN2 161:164 RPN2 161:164 RPN2 161:164 Various studies have found that silencing ribophorin II (RPN2) inhibits cell growth in several cancers. 29069815 4 51 theme increased 755:763 arg1 growth 770:775 increased cell growth 755:775 increased cell growth 755:775 We found that RPN2 silencing reduced glycosylation of EGFR, a highly N-link glycosylated cell surface glycoprotein that plays a critical role in majority of human cancers correlating with increased cell growth, proliferation, and differentiation. 29069815 8 52 theme new 1245:1247 arg1 target 1261:1266 a new therapeutic target 1243:1266 a new therapeutic target 1243:1266 Therefore, RPN2 may be a new therapeutic target and prognostic biomarker for CRC. 29069815 8 52 theme new 1245:1247 arg1 RPN2 1231:1234 RPN2 1231:1234 RPN2 1231:1234 Therefore, RPN2 may be a new therapeutic target and prognostic biomarker for CRC. 29069815 4 53 theme human 724:728 arg1 cancers 730:736 human cancers 724:736 human cancers correlating with increased cell growth, proliferation, and differentiation 724:811 We found that RPN2 silencing reduced glycosylation of EGFR, a highly N-link glycosylated cell surface glycoprotein that plays a critical role in majority of human cancers correlating with increased cell growth, proliferation, and differentiation. 29069815 1 54 theme silencing 136:144 arg1 II 157:158 silencing ribophorin II 136:158 silencing ribophorin II (RPN2) 136:165 Various studies have found that silencing ribophorin II (RPN2) inhibits cell growth in several cancers. 29069815 1 54 theme silencing 136:144 arg1 RPN2 161:164 RPN2 161:164 RPN2 161:164 Various studies have found that silencing ribophorin II (RPN2) inhibits cell growth in several cancers. 29069815 0 55 theme glycosylation 74:86 arg1 status 88:93 the glycosylation status 70:93 the glycosylation status of EGFR 70:101 RPN2 promotes colorectal cancer cell proliferation through modulating the glycosylation status of EGFR. 29069815 1 56 from growth 181:186 arg1 cancers 199:205 several cancers 191:205 several cancers 191:205 Various studies have found that silencing ribophorin II (RPN2) inhibits cell growth in several cancers. 29069815 3 57 theme cancer 503:508 arg1 cycle 521:525 colorectal cancer (CRC) cell cycle 492:525 colorectal cancer (CRC) cell cycle 492:525 Herein, we reveal that downregulation of RPN2, which may be a crucial regulator of N-linked glycosylation in cancer cells and drug-resistant cancer cells, promoted the progression of colorectal cancer (CRC) cell cycle and proliferation in vitro and in vivo. 29069815 5 58 theme RPN2 827:830 arg1 knockdown 832:840 RPN2 knockdown 827:840 RPN2 knockdown 827:840 In addition, RPN2 knockdown decreased EGFR expression and cell surface transport by EGFR deglycosylation. 29069815 4 59 theme RPN2 581:584 arg1 silencing 586:594 RPN2 silencing 581:594 RPN2 silencing 581:594 We found that RPN2 silencing reduced glycosylation of EGFR, a highly N-link glycosylated cell surface glycoprotein that plays a critical role in majority of human cancers correlating with increased cell growth, proliferation, and differentiation. 29069815 4 60 theme cell 765:768 arg1 growth 770:775 increased cell growth 755:775 increased cell growth 755:775 We found that RPN2 silencing reduced glycosylation of EGFR, a highly N-link glycosylated cell surface glycoprotein that plays a critical role in majority of human cancers correlating with increased cell growth, proliferation, and differentiation. 29069815 6 61 theme cell 977:980 arg1 proliferation 982:994 CRC cell proliferation 973:994 CRC cell proliferation 973:994 In summary, our findings suggest that RPN2 regulates CRC cell proliferation through mediating the glycosylation of EGFR which affecting the EGFR/ERK signaling pathways. 24799377 1 0 attach attachment 115:124 arg1 threonine 163:171 threonine 163:171 threonine 163:171 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation, the covalent attachment of N-acetylglucosamine to serine and threonine residues of proteins, is a post-translational modification that shares many features with protein phosphorylation. 24799377 1 0 attach attachment 115:124 arg1 serine 152:157 serine 152:157 serine 152:157 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation, the covalent attachment of N-acetylglucosamine to serine and threonine residues of proteins, is a post-translational modification that shares many features with protein phosphorylation. 24799377 1 0 attach attachment 115:124 arg2 N-acetylglucosamine 129:147 N-acetylglucosamine 129:147 N-acetylglucosamine 129:147 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation, the covalent attachment of N-acetylglucosamine to serine and threonine residues of proteins, is a post-translational modification that shares many features with protein phosphorylation. 24799377 1 1 theme protein 263:269 arg1 phosphorylation 271:285 protein phosphorylation 263:285 protein phosphorylation 263:285 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation, the covalent attachment of N-acetylglucosamine to serine and threonine residues of proteins, is a post-translational modification that shares many features with protein phosphorylation. 24799377 2 2 theme cell 314:317 arg1 survival 319:326 cell survival 314:326 cell survival 314:326 O-GlcNAc is essential for cell survival and plays important role in many biological processes (e.g. transcription, translation, cell division) and human diseases (e.g. diabetes, Alzheimer's disease, cancer). 24799377 4 3 theme radioisotope 749:760 arg1 S 766:766 the radioisotope (35)S 745:766 the radioisotope (35)S 745:766 Here, a method for O-GlcNAc detection using in vitro sulfation with two N-acetylglucosamine (GlcNAc)-specific sulfotransferases, carbohydrate sulfotransferase 2 and carbohydrate sulfotransferase 4, and the radioisotope (35)S is described. 24799377 2 4 dep processes 372:380 arg1 translation 403:413 translation 403:413 translation 403:413 O-GlcNAc is essential for cell survival and plays important role in many biological processes (e.g. transcription, translation, cell division) and human diseases (e.g. diabetes, Alzheimer's disease, cancer). 24799377 2 4 dep processes 372:380 arg1 division 421:428 cell division 416:428 cell division 416:428 O-GlcNAc is essential for cell survival and plays important role in many biological processes (e.g. transcription, translation, cell division) and human diseases (e.g. diabetes, Alzheimer's disease, cancer). 24799377 2 4 dep processes 372:380 arg1 transcription 388:400 transcription 388:400 transcription 388:400 O-GlcNAc is essential for cell survival and plays important role in many biological processes (e.g. transcription, translation, cell division) and human diseases (e.g. diabetes, Alzheimer's disease, cancer). 24799377 5 5 theme nuclear 883:889 arg1 proteins 907:914 nuclear and cytoplasmic proteins 883:914 peptides as well as nuclear and cytoplasmic proteins 863:914 Sulfation on free GlcNAc is first demonstrated, and then on O-GlcNAc residues of peptides as well as nuclear and cytoplasmic proteins. 24799377 7 6 theme sulfate-polyacrylamide 1087:1108 arg1 electrophoresis 1114:1128 sodium dodecyl sulfate-polyacrylamide gel electrophoresis 1072:1128 sodium dodecyl sulfate-polyacrylamide gel electrophoresis 1072:1128 The labeled samples are separated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and visualized by autoradiography. 24799377 1 7 theme O-GlcNAc 77:84 arg1 attachment 115:124 the covalent attachment 102:124 the covalent attachment of N-acetylglucosamine to serine and threonine residues of proteins 102:192 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation, the covalent attachment of N-acetylglucosamine to serine and threonine residues of proteins, is a post-translational modification that shares many features with protein phosphorylation. 24799377 1 7 theme O-GlcNAc 77:84 arg1 modification 219:230 a post-translational modification 198:230 a post-translational modification that shares many features with protein phosphorylation 198:285 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation, the covalent attachment of N-acetylglucosamine to serine and threonine residues of proteins, is a post-translational modification that shares many features with protein phosphorylation. 24799377 1 7 theme O-GlcNAc 77:84 arg1 glycosylation 87:99 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation 45:99 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation 45:99 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation, the covalent attachment of N-acetylglucosamine to serine and threonine residues of proteins, is a post-translational modification that shares many features with protein phosphorylation. 24799377 5 8 theme cytoplasmic 895:905 arg1 proteins 907:914 nuclear and cytoplasmic proteins 883:914 peptides as well as nuclear and cytoplasmic proteins 863:914 Sulfation on free GlcNAc is first demonstrated, and then on O-GlcNAc residues of peptides as well as nuclear and cytoplasmic proteins. 24799377 2 9 theme cell 416:419 arg1 division 421:428 cell division 416:428 cell division 416:428 O-GlcNAc is essential for cell survival and plays important role in many biological processes (e.g. transcription, translation, cell division) and human diseases (e.g. diabetes, Alzheimer's disease, cancer). 24799377 2 9 theme cell 416:419 arg1 transcription 388:400 transcription 388:400 transcription 388:400 O-GlcNAc is essential for cell survival and plays important role in many biological processes (e.g. transcription, translation, cell division) and human diseases (e.g. diabetes, Alzheimer's disease, cancer). 24799377 4 10 theme O-GlcNAc 562:569 arg1 detection 571:579 O-GlcNAc detection 562:579 O-GlcNAc detection using in vitro sulfation with two N-acetylglucosamine (GlcNAc)-specific sulfotransferases, carbohydrate sulfotransferase 2 and carbohydrate sulfotransferase 4, and the radioisotope (35)S 562:766 Here, a method for O-GlcNAc detection using in vitro sulfation with two N-acetylglucosamine (GlcNAc)-specific sulfotransferases, carbohydrate sulfotransferase 2 and carbohydrate sulfotransferase 4, and the radioisotope (35)S is described. 24799377 4 11 theme in 587:588 arg1 sulfation 596:604 in vitro sulfation 587:604 in vitro sulfation 587:604 Here, a method for O-GlcNAc detection using in vitro sulfation with two N-acetylglucosamine (GlcNAc)-specific sulfotransferases, carbohydrate sulfotransferase 2 and carbohydrate sulfotransferase 4, and the radioisotope (35)S is described. 24799377 1 12 theme proteins 185:192 arg1 threonine 163:171 threonine 163:171 threonine 163:171 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation, the covalent attachment of N-acetylglucosamine to serine and threonine residues of proteins, is a post-translational modification that shares many features with protein phosphorylation. 24799377 1 12 theme proteins 185:192 arg1 serine 152:157 serine 152:157 serine 152:157 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation, the covalent attachment of N-acetylglucosamine to serine and threonine residues of proteins, is a post-translational modification that shares many features with protein phosphorylation. 24799377 5 13 theme free 795:798 arg1 GlcNAc 800:805 free GlcNAc 795:805 free GlcNAc 795:805 Sulfation on free GlcNAc is first demonstrated, and then on O-GlcNAc residues of peptides as well as nuclear and cytoplasmic proteins. 24799377 2 14 dep diabetes 456:463 arg1 e.g. 451:454 e.g. 451:454 e.g. 451:454 O-GlcNAc is essential for cell survival and plays important role in many biological processes (e.g. transcription, translation, cell division) and human diseases (e.g. diabetes, Alzheimer's disease, cancer). 24799377 2 15 theme important 338:346 arg1 role 348:351 important role 338:351 important role 338:351 O-GlcNAc is essential for cell survival and plays important role in many biological processes (e.g. transcription, translation, cell division) and human diseases (e.g. diabetes, Alzheimer's disease, cancer). 24799377 3 16 theme O-GlcNAc 518:525 arg1 detection 505:513 detection 505:513 detection of O-GlcNAc 505:525 However, detection of O-GlcNAc is challenging. 24799377 1 17 link O-linked 45:52 arg1 attachment 115:124 the covalent attachment 102:124 the covalent attachment of N-acetylglucosamine to serine and threonine residues of proteins 102:192 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation, the covalent attachment of N-acetylglucosamine to serine and threonine residues of proteins, is a post-translational modification that shares many features with protein phosphorylation. 24799377 1 17 link O-linked 45:52 arg1 modification 219:230 a post-translational modification 198:230 a post-translational modification that shares many features with protein phosphorylation 198:285 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation, the covalent attachment of N-acetylglucosamine to serine and threonine residues of proteins, is a post-translational modification that shares many features with protein phosphorylation. 24799377 1 17 link O-linked 45:52 arg1 glycosylation 87:99 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation 45:99 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation 45:99 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation, the covalent attachment of N-acetylglucosamine to serine and threonine residues of proteins, is a post-translational modification that shares many features with protein phosphorylation. 24799377 0 18 theme in 25:26 arg1 sulfation 34:42 in vitro sulfation 25:42 in vitro sulfation 25:42 Detecting O-GlcNAc using in vitro sulfation. 24799377 1 19 dep serine 152:157 arg1 residues 173:180 residues 173:180 residues 173:180 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation, the covalent attachment of N-acetylglucosamine to serine and threonine residues of proteins, is a post-translational modification that shares many features with protein phosphorylation. 24799377 2 20 theme human 435:439 arg1 diseases 441:448 human diseases 435:448 human diseases (e.g. diabetes, Alzheimer's disease, cancer) 435:493 O-GlcNAc is essential for cell survival and plays important role in many biological processes (e.g. transcription, translation, cell division) and human diseases (e.g. diabetes, Alzheimer's disease, cancer). 24799377 2 21 dep transcription 388:400 arg1 e.g. 383:386 e.g. 383:386 e.g. 383:386 O-GlcNAc is essential for cell survival and plays important role in many biological processes (e.g. transcription, translation, cell division) and human diseases (e.g. diabetes, Alzheimer's disease, cancer). 24799377 1 22 theme covalent 106:113 arg1 attachment 115:124 the covalent attachment 102:124 the covalent attachment of N-acetylglucosamine to serine and threonine residues of proteins 102:192 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation, the covalent attachment of N-acetylglucosamine to serine and threonine residues of proteins, is a post-translational modification that shares many features with protein phosphorylation. 24799377 1 22 theme covalent 106:113 arg1 glycosylation 87:99 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation 45:99 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation 45:99 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation, the covalent attachment of N-acetylglucosamine to serine and threonine residues of proteins, is a post-translational modification that shares many features with protein phosphorylation. 24799377 1 23 theme post-translational 200:217 arg1 modification 219:230 a post-translational modification 198:230 a post-translational modification that shares many features with protein phosphorylation 198:285 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation, the covalent attachment of N-acetylglucosamine to serine and threonine residues of proteins, is a post-translational modification that shares many features with protein phosphorylation. 24799377 1 23 theme post-translational 200:217 arg1 glycosylation 87:99 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation 45:99 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation 45:99 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation, the covalent attachment of N-acetylglucosamine to serine and threonine residues of proteins, is a post-translational modification that shares many features with protein phosphorylation. 24799377 4 24 theme carbohydrate 708:719 arg1 sulfotransferase 721:736 carbohydrate sulfotransferase 4 708:738 carbohydrate sulfotransferase 4 708:738 Here, a method for O-GlcNAc detection using in vitro sulfation with two N-acetylglucosamine (GlcNAc)-specific sulfotransferases, carbohydrate sulfotransferase 2 and carbohydrate sulfotransferase 4, and the radioisotope (35)S is described. 24799377 4 24 theme carbohydrate 708:719 arg1 sulfotransferases 653:669 two N-acetylglucosamine (GlcNAc)-specific sulfotransferases 611:669 two N-acetylglucosamine (GlcNAc)-specific sulfotransferases 611:669 Here, a method for O-GlcNAc detection using in vitro sulfation with two N-acetylglucosamine (GlcNAc)-specific sulfotransferases, carbohydrate sulfotransferase 2 and carbohydrate sulfotransferase 4, and the radioisotope (35)S is described. 24799377 6 25 from sulfation 950:958 arg1 O-GlcNAc 963:970 O-GlcNAc 963:970 O-GlcNAc 963:970 It is also demonstrated that the sulfation on O-GlcNAc is sensitive to OGT and O-β-N-acetylglucosaminidase treatment. 24799377 4 26 theme -specific 643:651 arg1 sulfotransferase 721:736 carbohydrate sulfotransferase 4 708:738 carbohydrate sulfotransferase 4 708:738 Here, a method for O-GlcNAc detection using in vitro sulfation with two N-acetylglucosamine (GlcNAc)-specific sulfotransferases, carbohydrate sulfotransferase 2 and carbohydrate sulfotransferase 4, and the radioisotope (35)S is described. 24799377 4 26 theme -specific 643:651 arg1 sulfotransferases 653:669 two N-acetylglucosamine (GlcNAc)-specific sulfotransferases 611:669 two N-acetylglucosamine (GlcNAc)-specific sulfotransferases 611:669 Here, a method for O-GlcNAc detection using in vitro sulfation with two N-acetylglucosamine (GlcNAc)-specific sulfotransferases, carbohydrate sulfotransferase 2 and carbohydrate sulfotransferase 4, and the radioisotope (35)S is described. 24799377 4 26 theme -specific 643:651 arg1 sulfotransferase 685:700 carbohydrate sulfotransferase 2 672:702 carbohydrate sulfotransferase 2 672:702 Here, a method for O-GlcNAc detection using in vitro sulfation with two N-acetylglucosamine (GlcNAc)-specific sulfotransferases, carbohydrate sulfotransferase 2 and carbohydrate sulfotransferase 4, and the radioisotope (35)S is described. 24799377 2 27 theme biological 361:370 arg1 processes 372:380 many biological processes 356:380 many biological processes (e.g. transcription, translation, cell division) 356:429 O-GlcNAc is essential for cell survival and plays important role in many biological processes (e.g. transcription, translation, cell division) and human diseases (e.g. diabetes, Alzheimer's disease, cancer). 24799377 7 28 theme labeled 1039:1045 arg1 samples 1047:1053 The labeled samples 1035:1053 The labeled samples 1035:1053 The labeled samples are separated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and visualized by autoradiography. 24799377 7 29 theme gel 1110:1112 arg1 electrophoresis 1114:1128 sodium dodecyl sulfate-polyacrylamide gel electrophoresis 1072:1128 sodium dodecyl sulfate-polyacrylamide gel electrophoresis 1072:1128 The labeled samples are separated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and visualized by autoradiography. 24799377 2 30 theme many 356:359 arg1 processes 372:380 many biological processes 356:380 many biological processes (e.g. transcription, translation, cell division) 356:429 O-GlcNAc is essential for cell survival and plays important role in many biological processes (e.g. transcription, translation, cell division) and human diseases (e.g. diabetes, Alzheimer's disease, cancer). 24799377 0 31 dep in 25:26 arg1 vitro 28:32 vitro 28:32 vitro 28:32 Detecting O-GlcNAc using in vitro sulfation. 24799377 1 32 theme N-acetylglucosamine 129:147 arg1 attachment 115:124 the covalent attachment 102:124 the covalent attachment of N-acetylglucosamine to serine and threonine residues of proteins 102:192 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation, the covalent attachment of N-acetylglucosamine to serine and threonine residues of proteins, is a post-translational modification that shares many features with protein phosphorylation. 24799377 1 32 theme N-acetylglucosamine 129:147 arg1 glycosylation 87:99 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation 45:99 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation 45:99 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation, the covalent attachment of N-acetylglucosamine to serine and threonine residues of proteins, is a post-translational modification that shares many features with protein phosphorylation. 24799377 6 33 theme O-β-N-acetylglucosaminidase 996:1022 arg1 treatment 1024:1032 O-β-N-acetylglucosaminidase treatment 996:1032 O-β-N-acetylglucosaminidase treatment 996:1032 It is also demonstrated that the sulfation on O-GlcNAc is sensitive to OGT and O-β-N-acetylglucosaminidase treatment. 24799377 1 34 theme β-N-acetylglucosamine 54:74 arg1 attachment 115:124 the covalent attachment 102:124 the covalent attachment of N-acetylglucosamine to serine and threonine residues of proteins 102:192 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation, the covalent attachment of N-acetylglucosamine to serine and threonine residues of proteins, is a post-translational modification that shares many features with protein phosphorylation. 24799377 1 34 theme β-N-acetylglucosamine 54:74 arg1 modification 219:230 a post-translational modification 198:230 a post-translational modification that shares many features with protein phosphorylation 198:285 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation, the covalent attachment of N-acetylglucosamine to serine and threonine residues of proteins, is a post-translational modification that shares many features with protein phosphorylation. 24799377 1 34 theme β-N-acetylglucosamine 54:74 arg1 glycosylation 87:99 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation 45:99 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation 45:99 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation, the covalent attachment of N-acetylglucosamine to serine and threonine residues of proteins, is a post-translational modification that shares many features with protein phosphorylation. 24799377 5 35 theme proteins 907:914 arg1 peptides 863:870 peptides 863:870 peptides as well as nuclear and cytoplasmic proteins 863:914 Sulfation on free GlcNAc is first demonstrated, and then on O-GlcNAc residues of peptides as well as nuclear and cytoplasmic proteins. 24799377 5 35 theme proteins 907:914 arg1 residues 851:858 O-GlcNAc residues 842:858 O-GlcNAc residues of peptides as well as nuclear and cytoplasmic proteins 842:914 Sulfation on free GlcNAc is first demonstrated, and then on O-GlcNAc residues of peptides as well as nuclear and cytoplasmic proteins. 24799377 5 35 theme proteins 907:914 arg1 proteins 907:914 nuclear and cytoplasmic proteins 883:914 peptides as well as nuclear and cytoplasmic proteins 863:914 Sulfation on free GlcNAc is first demonstrated, and then on O-GlcNAc residues of peptides as well as nuclear and cytoplasmic proteins. 24799377 1 36 theme many 244:247 arg1 features 249:256 many features 244:256 many features 244:256 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation, the covalent attachment of N-acetylglucosamine to serine and threonine residues of proteins, is a post-translational modification that shares many features with protein phosphorylation. 24799377 4 37 dep in 587:588 arg1 vitro 590:594 vitro 590:594 vitro 590:594 Here, a method for O-GlcNAc detection using in vitro sulfation with two N-acetylglucosamine (GlcNAc)-specific sulfotransferases, carbohydrate sulfotransferase 2 and carbohydrate sulfotransferase 4, and the radioisotope (35)S is described. 24799377 5 38 theme peptides 863:870 arg1 peptides 863:870 peptides 863:870 peptides as well as nuclear and cytoplasmic proteins 863:914 Sulfation on free GlcNAc is first demonstrated, and then on O-GlcNAc residues of peptides as well as nuclear and cytoplasmic proteins. 24799377 5 38 theme peptides 863:870 arg1 residues 851:858 O-GlcNAc residues 842:858 O-GlcNAc residues of peptides as well as nuclear and cytoplasmic proteins 842:914 Sulfation on free GlcNAc is first demonstrated, and then on O-GlcNAc residues of peptides as well as nuclear and cytoplasmic proteins. 24799377 5 38 theme peptides 863:870 arg1 proteins 907:914 nuclear and cytoplasmic proteins 883:914 peptides as well as nuclear and cytoplasmic proteins 863:914 Sulfation on free GlcNAc is first demonstrated, and then on O-GlcNAc residues of peptides as well as nuclear and cytoplasmic proteins. 24799377 5 39 theme O-GlcNAc 842:849 arg1 peptides 863:870 peptides 863:870 peptides as well as nuclear and cytoplasmic proteins 863:914 Sulfation on free GlcNAc is first demonstrated, and then on O-GlcNAc residues of peptides as well as nuclear and cytoplasmic proteins. 24799377 5 39 theme O-GlcNAc 842:849 arg1 residues 851:858 O-GlcNAc residues 842:858 O-GlcNAc residues of peptides as well as nuclear and cytoplasmic proteins 842:914 Sulfation on free GlcNAc is first demonstrated, and then on O-GlcNAc residues of peptides as well as nuclear and cytoplasmic proteins. 24799377 5 39 theme O-GlcNAc 842:849 arg1 proteins 907:914 nuclear and cytoplasmic proteins 883:914 peptides as well as nuclear and cytoplasmic proteins 863:914 Sulfation on free GlcNAc is first demonstrated, and then on O-GlcNAc residues of peptides as well as nuclear and cytoplasmic proteins. 24799377 5 40 from Sulfation 782:790 arg1 GlcNAc 800:805 free GlcNAc 795:805 free GlcNAc 795:805 Sulfation on free GlcNAc is first demonstrated, and then on O-GlcNAc residues of peptides as well as nuclear and cytoplasmic proteins. 24799377 1 41 theme O-linked 45:52 arg1 attachment 115:124 the covalent attachment 102:124 the covalent attachment of N-acetylglucosamine to serine and threonine residues of proteins 102:192 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation, the covalent attachment of N-acetylglucosamine to serine and threonine residues of proteins, is a post-translational modification that shares many features with protein phosphorylation. 24799377 1 41 theme O-linked 45:52 arg1 modification 219:230 a post-translational modification 198:230 a post-translational modification that shares many features with protein phosphorylation 198:285 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation, the covalent attachment of N-acetylglucosamine to serine and threonine residues of proteins, is a post-translational modification that shares many features with protein phosphorylation. 24799377 1 41 theme O-linked 45:52 arg1 glycosylation 87:99 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation 45:99 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation 45:99 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation, the covalent attachment of N-acetylglucosamine to serine and threonine residues of proteins, is a post-translational modification that shares many features with protein phosphorylation. 24799377 4 42 theme carbohydrate 672:683 arg1 sulfotransferases 653:669 two N-acetylglucosamine (GlcNAc)-specific sulfotransferases 611:669 two N-acetylglucosamine (GlcNAc)-specific sulfotransferases 611:669 Here, a method for O-GlcNAc detection using in vitro sulfation with two N-acetylglucosamine (GlcNAc)-specific sulfotransferases, carbohydrate sulfotransferase 2 and carbohydrate sulfotransferase 4, and the radioisotope (35)S is described. 24799377 4 42 theme carbohydrate 672:683 arg1 sulfotransferase 685:700 carbohydrate sulfotransferase 2 672:702 carbohydrate sulfotransferase 2 672:702 Here, a method for O-GlcNAc detection using in vitro sulfation with two N-acetylglucosamine (GlcNAc)-specific sulfotransferases, carbohydrate sulfotransferase 2 and carbohydrate sulfotransferase 4, and the radioisotope (35)S is described. 24536041 0 0 theme human 69:73 arg1 microarray 84:93 a human proteome microarray 67:93 a human proteome microarray 67:93 Global identification of O-GlcNAc transferase (OGT) interactors by a human proteome microarray and the construction of an OGT interactome. 24536041 1 1 theme O-Linked 139:146 arg1 PTM 212:214 an important protein PTM 191:214 an important protein PTM 191:214 O-Linked β-N-acetylglucosamine (O-GlcNAcylation) is an important protein PTM, which is very abundant in mammalian cells. 24536041 1 1 theme O-Linked 139:146 arg1 O-GlcNAcylation 171:185 O-GlcNAcylation 171:185 O-GlcNAcylation 171:185 O-Linked β-N-acetylglucosamine (O-GlcNAcylation) is an important protein PTM, which is very abundant in mammalian cells. 24536041 1 1 theme O-Linked 139:146 arg1 abundant 231:238 abundant 231:238 abundant 231:238 O-Linked β-N-acetylglucosamine (O-GlcNAcylation) is an important protein PTM, which is very abundant in mammalian cells. 24536041 1 1 theme O-Linked 139:146 arg1 β-N-acetylglucosamine 148:168 O-Linked β-N-acetylglucosamine 139:168 O-Linked β-N-acetylglucosamine (O-GlcNAcylation) 139:186 O-Linked β-N-acetylglucosamine (O-GlcNAcylation) is an important protein PTM, which is very abundant in mammalian cells. 24536041 4 2 used used 581:584 arg2 we 578:579 we 578:579 we 578:579 To address this challenge, we used a human proteome microarray containing ~17,000 affinity-purified human proteins to globally identify OGT interactors and identified 25 OGT-binding proteins. 24536041 7 3 theme OGT 1155:1157 arg1 interactome 1159:1169 the OGT interactome 1151:1169 the OGT interactome 1151:1169 Bioinformatics analysis suggests that the OGT interactome plays important roles in protein transportation/localization and transcriptional regulation. 24536041 5 4 from enriched 883:890 arg1 processes 959:967 vitamin biosynthetic processes 938:967 vitamin biosynthetic processes 938:967 Bioinformatics analysis showed that these interacting proteins play a variety of roles in a wide range of cellular functions and are highly enriched in intra-Golgi vesicle-mediated transport and vitamin biosynthetic processes. 24536041 5 4 from enriched 883:890 arg1 transport 924:932 intra-Golgi vesicle-mediated transport 895:932 intra-Golgi vesicle-mediated transport 895:932 Bioinformatics analysis showed that these interacting proteins play a variety of roles in a wide range of cellular functions and are highly enriched in intra-Golgi vesicle-mediated transport and vitamin biosynthetic processes. 24536041 2 5 theme substrate 326:334 arg1 specificity 336:346 specificity 336:346 specificity 336:346 O-GlcNAcylation is catalyzed by O-GlcNAc transferase (OGT), whose substrate specificity is believed to be regulated through interactions with other proteins. 24536041 9 6 theme regulators 1555:1564 arg1 identification 1537:1550 the global identification 1526:1550 the global identification of regulators for other key enzymes 1526:1586 Because of its high-throughput and parallel analysis capability, we strongly believe that protein microarrays could be easily applied for the global identification of regulators for other key enzymes. 24536041 5 7 theme vitamin 938:944 arg1 processes 959:967 vitamin biosynthetic processes 938:967 vitamin biosynthetic processes 938:967 Bioinformatics analysis showed that these interacting proteins play a variety of roles in a wide range of cellular functions and are highly enriched in intra-Golgi vesicle-mediated transport and vitamin biosynthetic processes. 24536041 7 8 theme Bioinformatics 1113:1126 arg1 analysis 1128:1135 Bioinformatics analysis 1113:1135 Bioinformatics analysis 1113:1135 Bioinformatics analysis suggests that the OGT interactome plays important roles in protein transportation/localization and transcriptional regulation. 24536041 1 9 theme mammalian 243:251 arg1 cells 253:257 mammalian cells 243:257 mammalian cells 243:257 O-Linked β-N-acetylglucosamine (O-GlcNAcylation) is an important protein PTM, which is very abundant in mammalian cells. 24536041 0 10 theme proteome 75:82 arg1 microarray 84:93 a human proteome microarray 67:93 a human proteome microarray 67:93 Global identification of O-GlcNAc transferase (OGT) interactors by a human proteome microarray and the construction of an OGT interactome. 24536041 9 11 theme key 1576:1578 arg1 enzymes 1580:1586 other key enzymes 1570:1586 other key enzymes 1570:1586 Because of its high-throughput and parallel analysis capability, we strongly believe that protein microarrays could be easily applied for the global identification of regulators for other key enzymes. 24536041 7 12 theme transcriptional 1236:1250 arg1 regulation 1252:1261 transcriptional regulation 1236:1261 transcriptional regulation 1236:1261 Bioinformatics analysis suggests that the OGT interactome plays important roles in protein transportation/localization and transcriptional regulation. 24536041 2 13 with interactions 384:395 arg1 proteins 408:415 other proteins 402:415 other proteins 402:415 O-GlcNAcylation is catalyzed by O-GlcNAc transferase (OGT), whose substrate specificity is believed to be regulated through interactions with other proteins. 24536041 5 14 theme biosynthetic 946:957 arg1 processes 959:967 vitamin biosynthetic processes 938:967 vitamin biosynthetic processes 938:967 Bioinformatics analysis showed that these interacting proteins play a variety of roles in a wide range of cellular functions and are highly enriched in intra-Golgi vesicle-mediated transport and vitamin biosynthetic processes. 24536041 2 15 theme other 402:406 arg1 proteins 408:415 other proteins 402:415 other proteins 402:415 O-GlcNAcylation is catalyzed by O-GlcNAc transferase (OGT), whose substrate specificity is believed to be regulated through interactions with other proteins. 24536041 5 16 theme functions 858:866 arg1 range 840:844 a wide range 833:844 a wide range of cellular functions 833:866 Bioinformatics analysis showed that these interacting proteins play a variety of roles in a wide range of cellular functions and are highly enriched in intra-Golgi vesicle-mediated transport and vitamin biosynthetic processes. 24536041 6 17 theme OGT 1096:1098 arg1 interactome 1100:1110 the first OGT interactome 1086:1110 the first OGT interactome 1086:1110 Combining newly identified OGT interactors with the interactors identified prior to this study, we have constructed the first OGT interactome. 24536041 9 18 theme protein 1478:1484 arg1 microarrays 1486:1496 protein microarrays 1478:1496 protein microarrays 1478:1496 Because of its high-throughput and parallel analysis capability, we strongly believe that protein microarrays could be easily applied for the global identification of regulators for other key enzymes. 24536041 8 19 theme OGT 1274:1276 arg1 point 1349:1353 a starting point 1338:1353 a starting point for further functional analysis 1338:1385 The novel OGT interactors that we identified in this study could serve as a starting point for further functional analysis. 24536041 8 19 theme OGT 1274:1276 arg1 interactors 1278:1288 The novel OGT interactors 1264:1288 The novel OGT interactors that we identified in this study 1264:1321 The novel OGT interactors that we identified in this study could serve as a starting point for further functional analysis. 24536041 5 20 from transport 924:932 arg1 enriched 883:890 enriched 883:890 enriched 883:890 Bioinformatics analysis showed that these interacting proteins play a variety of roles in a wide range of cellular functions and are highly enriched in intra-Golgi vesicle-mediated transport and vitamin biosynthetic processes. 24536041 0 21 theme Global 0:5 arg1 identification 7:20 Global identification 0:20 Global identification of O-GlcNAc transferase (OGT) interactors by a human proteome microarray 0:93 Global identification of O-GlcNAc transferase (OGT) interactors by a human proteome microarray and the construction of an OGT interactome. 24536041 5 22 theme cellular 849:856 arg1 functions 858:866 cellular functions 849:866 cellular functions 849:866 Bioinformatics analysis showed that these interacting proteins play a variety of roles in a wide range of cellular functions and are highly enriched in intra-Golgi vesicle-mediated transport and vitamin biosynthetic processes. 24536041 9 23 theme high-throughput 1403:1417 arg1 capability 1441:1450 its high-throughput and parallel analysis capability 1399:1450 its high-throughput and parallel analysis capability 1399:1450 Because of its high-throughput and parallel analysis capability, we strongly believe that protein microarrays could be easily applied for the global identification of regulators for other key enzymes. 24536041 4 24 theme OGT-binding 721:731 arg1 proteins 733:740 25 OGT-binding proteins 718:740 25 OGT-binding proteins 718:740 To address this challenge, we used a human proteome microarray containing ~17,000 affinity-purified human proteins to globally identify OGT interactors and identified 25 OGT-binding proteins. 24536041 4 25 theme human 651:655 arg1 proteins 657:664 ~17,000 affinity-purified human proteins 625:664 ~17,000 affinity-purified human proteins 625:664 To address this challenge, we used a human proteome microarray containing ~17,000 affinity-purified human proteins to globally identify OGT interactors and identified 25 OGT-binding proteins. 24536041 1 26 from abundant 231:238 arg1 cells 253:257 mammalian cells 243:257 mammalian cells 243:257 O-Linked β-N-acetylglucosamine (O-GlcNAcylation) is an important protein PTM, which is very abundant in mammalian cells. 24536041 6 27 theme OGT 997:999 arg1 interactors 1001:1011 newly identified OGT interactors 980:1011 newly identified OGT interactors 980:1011 Combining newly identified OGT interactors with the interactors identified prior to this study, we have constructed the first OGT interactome. 24536041 3 28 theme OGT 546:548 arg1 specificity 531:541 the substrate specificity 517:541 the substrate specificity of OGT 517:548 There are a handful of known human OGT interactors, which is far from enough for fully elucidating the substrate specificity of OGT. 24536041 4 29 theme affinity-purified 633:649 arg1 proteins 657:664 ~17,000 affinity-purified human proteins 625:664 ~17,000 affinity-purified human proteins 625:664 To address this challenge, we used a human proteome microarray containing ~17,000 affinity-purified human proteins to globally identify OGT interactors and identified 25 OGT-binding proteins. 24536041 0 30 theme O-GlcNAc 25:32 arg1 OGT 47:49 OGT 47:49 OGT 47:49 Global identification of O-GlcNAc transferase (OGT) interactors by a human proteome microarray and the construction of an OGT interactome. 24536041 0 30 theme O-GlcNAc 25:32 arg1 transferase 34:44 O-GlcNAc transferase 25:44 O-GlcNAc transferase (OGT) interactors by a human proteome microarray 25:93 Global identification of O-GlcNAc transferase (OGT) interactors by a human proteome microarray and the construction of an OGT interactome. 24536041 6 31 theme identified 986:995 arg1 interactors 1001:1011 newly identified OGT interactors 980:1011 newly identified OGT interactors 980:1011 Combining newly identified OGT interactors with the interactors identified prior to this study, we have constructed the first OGT interactome. 24536041 5 32 theme intra-Golgi 895:905 arg1 transport 924:932 intra-Golgi vesicle-mediated transport 895:932 intra-Golgi vesicle-mediated transport 895:932 Bioinformatics analysis showed that these interacting proteins play a variety of roles in a wide range of cellular functions and are highly enriched in intra-Golgi vesicle-mediated transport and vitamin biosynthetic processes. 24536041 2 33 theme O-GlcNAc 292:299 arg1 OGT 314:316 OGT 314:316 OGT 314:316 O-GlcNAcylation is catalyzed by O-GlcNAc transferase (OGT), whose substrate specificity is believed to be regulated through interactions with other proteins. 24536041 2 33 theme O-GlcNAc 292:299 arg1 transferase 301:311 O-GlcNAc transferase 292:311 O-GlcNAc transferase (OGT) 292:317 O-GlcNAcylation is catalyzed by O-GlcNAc transferase (OGT), whose substrate specificity is believed to be regulated through interactions with other proteins. 24536041 3 34 theme known 441:445 arg1 interactors 457:467 known human OGT interactors 441:467 known human OGT interactors 441:467 There are a handful of known human OGT interactors, which is far from enough for fully elucidating the substrate specificity of OGT. 24536041 5 35 theme roles 824:828 arg1 variety 813:819 a variety 811:819 a variety of roles 811:828 Bioinformatics analysis showed that these interacting proteins play a variety of roles in a wide range of cellular functions and are highly enriched in intra-Golgi vesicle-mediated transport and vitamin biosynthetic processes. 24536041 5 35 theme roles 824:828 arg1 roles 824:828 roles 824:828 roles 824:828 Bioinformatics analysis showed that these interacting proteins play a variety of roles in a wide range of cellular functions and are highly enriched in intra-Golgi vesicle-mediated transport and vitamin biosynthetic processes. 24536041 1 36 from cells 253:257 arg1 β-N-acetylglucosamine 148:168 O-Linked β-N-acetylglucosamine 139:168 O-Linked β-N-acetylglucosamine (O-GlcNAcylation) 139:186 O-Linked β-N-acetylglucosamine (O-GlcNAcylation) is an important protein PTM, which is very abundant in mammalian cells. 24536041 1 36 from cells 253:257 arg1 abundant 231:238 abundant 231:238 abundant 231:238 O-Linked β-N-acetylglucosamine (O-GlcNAcylation) is an important protein PTM, which is very abundant in mammalian cells. 24536041 1 36 from cells 253:257 arg1 PTM 212:214 an important protein PTM 191:214 an important protein PTM 191:214 O-Linked β-N-acetylglucosamine (O-GlcNAcylation) is an important protein PTM, which is very abundant in mammalian cells. 24536041 1 37 theme important 194:202 arg1 β-N-acetylglucosamine 148:168 O-Linked β-N-acetylglucosamine 139:168 O-Linked β-N-acetylglucosamine (O-GlcNAcylation) 139:186 O-Linked β-N-acetylglucosamine (O-GlcNAcylation) is an important protein PTM, which is very abundant in mammalian cells. 24536041 1 37 theme important 194:202 arg1 abundant 231:238 abundant 231:238 abundant 231:238 O-Linked β-N-acetylglucosamine (O-GlcNAcylation) is an important protein PTM, which is very abundant in mammalian cells. 24536041 1 37 theme important 194:202 arg1 PTM 212:214 an important protein PTM 191:214 an important protein PTM 191:214 O-Linked β-N-acetylglucosamine (O-GlcNAcylation) is an important protein PTM, which is very abundant in mammalian cells. 24536041 7 38 theme important 1177:1185 arg1 roles 1187:1191 important roles 1177:1191 important roles 1177:1191 Bioinformatics analysis suggests that the OGT interactome plays important roles in protein transportation/localization and transcriptional regulation. 24536041 5 39 theme vesicle-mediated 907:922 arg1 transport 924:932 intra-Golgi vesicle-mediated transport 895:932 intra-Golgi vesicle-mediated transport 895:932 Bioinformatics analysis showed that these interacting proteins play a variety of roles in a wide range of cellular functions and are highly enriched in intra-Golgi vesicle-mediated transport and vitamin biosynthetic processes. 24536041 0 40 theme OGT 122:124 arg1 interactome 126:136 an OGT interactome 119:136 an OGT interactome 119:136 Global identification of O-GlcNAc transferase (OGT) interactors by a human proteome microarray and the construction of an OGT interactome. 24536041 5 41 theme wide 835:838 arg1 range 840:844 a wide range 833:844 a wide range of cellular functions 833:866 Bioinformatics analysis showed that these interacting proteins play a variety of roles in a wide range of cellular functions and are highly enriched in intra-Golgi vesicle-mediated transport and vitamin biosynthetic processes. 24536041 1 42 theme protein 204:210 arg1 β-N-acetylglucosamine 148:168 O-Linked β-N-acetylglucosamine 139:168 O-Linked β-N-acetylglucosamine (O-GlcNAcylation) 139:186 O-Linked β-N-acetylglucosamine (O-GlcNAcylation) is an important protein PTM, which is very abundant in mammalian cells. 24536041 1 42 theme protein 204:210 arg1 abundant 231:238 abundant 231:238 abundant 231:238 O-Linked β-N-acetylglucosamine (O-GlcNAcylation) is an important protein PTM, which is very abundant in mammalian cells. 24536041 1 42 theme protein 204:210 arg1 PTM 212:214 an important protein PTM 191:214 an important protein PTM 191:214 O-Linked β-N-acetylglucosamine (O-GlcNAcylation) is an important protein PTM, which is very abundant in mammalian cells. 24536041 0 43 theme transferase 34:44 arg1 interactors 52:62 O-GlcNAc transferase (OGT) interactors 25:62 O-GlcNAc transferase (OGT) interactors by a human proteome microarray 25:93 Global identification of O-GlcNAc transferase (OGT) interactors by a human proteome microarray and the construction of an OGT interactome. 24536041 5 44 theme interacting 785:795 arg1 proteins 797:804 these interacting proteins 779:804 these interacting proteins 779:804 Bioinformatics analysis showed that these interacting proteins play a variety of roles in a wide range of cellular functions and are highly enriched in intra-Golgi vesicle-mediated transport and vitamin biosynthetic processes. 24536041 4 45 theme proteome 594:601 arg1 microarray 603:612 a human proteome microarray 586:612 a human proteome microarray containing ~17,000 affinity-purified human proteins 586:664 To address this challenge, we used a human proteome microarray containing ~17,000 affinity-purified human proteins to globally identify OGT interactors and identified 25 OGT-binding proteins. 24536041 8 46 theme starting 1340:1347 arg1 point 1349:1353 a starting point 1338:1353 a starting point for further functional analysis 1338:1385 The novel OGT interactors that we identified in this study could serve as a starting point for further functional analysis. 24536041 8 46 theme starting 1340:1347 arg1 interactors 1278:1288 The novel OGT interactors 1264:1288 The novel OGT interactors that we identified in this study 1264:1321 The novel OGT interactors that we identified in this study could serve as a starting point for further functional analysis. 24536041 9 47 theme parallel 1423:1430 arg1 capability 1441:1450 its high-throughput and parallel analysis capability 1399:1450 its high-throughput and parallel analysis capability 1399:1450 Because of its high-throughput and parallel analysis capability, we strongly believe that protein microarrays could be easily applied for the global identification of regulators for other key enzymes. 24536041 8 48 theme novel 1268:1272 arg1 point 1349:1353 a starting point 1338:1353 a starting point for further functional analysis 1338:1385 The novel OGT interactors that we identified in this study could serve as a starting point for further functional analysis. 24536041 8 48 theme novel 1268:1272 arg1 interactors 1278:1288 The novel OGT interactors 1264:1288 The novel OGT interactors that we identified in this study 1264:1321 The novel OGT interactors that we identified in this study could serve as a starting point for further functional analysis. 24536041 3 49 theme human 447:451 arg1 interactors 457:467 known human OGT interactors 441:467 known human OGT interactors 441:467 There are a handful of known human OGT interactors, which is far from enough for fully elucidating the substrate specificity of OGT. 24536041 9 50 theme analysis 1432:1439 arg1 capability 1441:1450 its high-throughput and parallel analysis capability 1399:1450 its high-throughput and parallel analysis capability 1399:1450 Because of its high-throughput and parallel analysis capability, we strongly believe that protein microarrays could be easily applied for the global identification of regulators for other key enzymes. 24536041 0 51 theme interactome 126:136 arg1 construction 103:114 the construction 99:114 the construction of an OGT interactome 99:136 Global identification of O-GlcNAc transferase (OGT) interactors by a human proteome microarray and the construction of an OGT interactome. 24536041 0 51 theme interactome 126:136 arg1 identification 7:20 Global identification 0:20 Global identification of O-GlcNAc transferase (OGT) interactors by a human proteome microarray 0:93 Global identification of O-GlcNAc transferase (OGT) interactors by a human proteome microarray and the construction of an OGT interactome. 24536041 9 52 theme global 1530:1535 arg1 identification 1537:1550 the global identification 1526:1550 the global identification of regulators for other key enzymes 1526:1586 Because of its high-throughput and parallel analysis capability, we strongly believe that protein microarrays could be easily applied for the global identification of regulators for other key enzymes. 24536041 4 53 theme OGT 687:689 arg1 interactors 691:701 OGT interactors 687:701 OGT interactors 687:701 To address this challenge, we used a human proteome microarray containing ~17,000 affinity-purified human proteins to globally identify OGT interactors and identified 25 OGT-binding proteins. 24536041 5 54 from processes 959:967 arg1 enriched 883:890 enriched 883:890 enriched 883:890 Bioinformatics analysis showed that these interacting proteins play a variety of roles in a wide range of cellular functions and are highly enriched in intra-Golgi vesicle-mediated transport and vitamin biosynthetic processes. 24536041 3 55 theme OGT 453:455 arg1 interactors 457:467 known human OGT interactors 441:467 known human OGT interactors 441:467 There are a handful of known human OGT interactors, which is far from enough for fully elucidating the substrate specificity of OGT. 24536041 3 56 theme substrate 521:529 arg1 specificity 531:541 the substrate specificity 517:541 the substrate specificity of OGT 517:548 There are a handful of known human OGT interactors, which is far from enough for fully elucidating the substrate specificity of OGT. 24536041 4 57 contain containing 614:623 arg2 proteins 657:664 ~17,000 affinity-purified human proteins 625:664 ~17,000 affinity-purified human proteins 625:664 To address this challenge, we used a human proteome microarray containing ~17,000 affinity-purified human proteins to globally identify OGT interactors and identified 25 OGT-binding proteins. 24536041 4 57 contain containing 614:623 arg1 microarray 603:612 a human proteome microarray 586:612 a human proteome microarray containing ~17,000 affinity-purified human proteins 586:664 To address this challenge, we used a human proteome microarray containing ~17,000 affinity-purified human proteins to globally identify OGT interactors and identified 25 OGT-binding proteins. 24536041 3 58 theme interactors 457:467 arg1 handful 430:436 a handful 428:436 a handful 428:436 There are a handful of known human OGT interactors, which is far from enough for fully elucidating the substrate specificity of OGT. 24536041 3 58 theme interactors 457:467 arg1 enough 488:493 enough 488:493 enough 488:493 There are a handful of known human OGT interactors, which is far from enough for fully elucidating the substrate specificity of OGT. 24536041 9 59 theme other 1570:1574 arg1 enzymes 1580:1586 other key enzymes 1570:1586 other key enzymes 1570:1586 Because of its high-throughput and parallel analysis capability, we strongly believe that protein microarrays could be easily applied for the global identification of regulators for other key enzymes. 24536041 5 60 theme Bioinformatics 743:756 arg1 analysis 758:765 Bioinformatics analysis 743:765 Bioinformatics analysis 743:765 Bioinformatics analysis showed that these interacting proteins play a variety of roles in a wide range of cellular functions and are highly enriched in intra-Golgi vesicle-mediated transport and vitamin biosynthetic processes. 24536041 4 61 theme human 588:592 arg1 microarray 603:612 a human proteome microarray 586:612 a human proteome microarray containing ~17,000 affinity-purified human proteins 586:664 To address this challenge, we used a human proteome microarray containing ~17,000 affinity-purified human proteins to globally identify OGT interactors and identified 25 OGT-binding proteins. 24536041 8 62 theme functional 1367:1376 arg1 analysis 1378:1385 further functional analysis 1359:1385 further functional analysis 1359:1385 The novel OGT interactors that we identified in this study could serve as a starting point for further functional analysis. 24536041 6 63 theme first 1090:1094 arg1 interactome 1100:1110 the first OGT interactome 1086:1110 the first OGT interactome 1086:1110 Combining newly identified OGT interactors with the interactors identified prior to this study, we have constructed the first OGT interactome. 24536041 0 64 theme interactors 52:62 arg1 construction 103:114 the construction 99:114 the construction of an OGT interactome 99:136 Global identification of O-GlcNAc transferase (OGT) interactors by a human proteome microarray and the construction of an OGT interactome. 24536041 0 64 theme interactors 52:62 arg1 identification 7:20 Global identification 0:20 Global identification of O-GlcNAc transferase (OGT) interactors by a human proteome microarray 0:93 Global identification of O-GlcNAc transferase (OGT) interactors by a human proteome microarray and the construction of an OGT interactome. 24536041 7 65 theme protein 1196:1202 arg1 transportation/localization 1204:1230 protein transportation/localization 1196:1230 protein transportation/localization 1196:1230 Bioinformatics analysis suggests that the OGT interactome plays important roles in protein transportation/localization and transcriptional regulation. 24536041 8 66 theme further 1359:1365 arg1 analysis 1378:1385 further functional analysis 1359:1385 further functional analysis 1359:1385 The novel OGT interactors that we identified in this study could serve as a starting point for further functional analysis. 29175660 2 0 theme oligosaccharide 389:403 arg1 transfer 374:381 enzymatic transfer 364:381 enzymatic transfer of an oligosaccharide using the transglycosylation activity of the glycosynthase-like mutant of Mucor hiemalis endo-β-N-acetylglucosaminidase (Endo-M) and sialo-oligosaccharide oxazoline as a donor substrate 364:589 We synthesized the glycosylated glucagon by chemical synthesis of an N-acetylglucosaminyl peptide and enzymatic transfer of an oligosaccharide using the transglycosylation activity of the glycosynthase-like mutant of Mucor hiemalis endo-β-N-acetylglucosaminidase (Endo-M) and sialo-oligosaccharide oxazoline as a donor substrate. 29175660 2 0 theme oligosaccharide 389:403 arg1 synthesis 315:323 chemical synthesis 306:323 chemical synthesis of an N-acetylglucosaminyl peptide 306:358 We synthesized the glycosylated glucagon by chemical synthesis of an N-acetylglucosaminyl peptide and enzymatic transfer of an oligosaccharide using the transglycosylation activity of the glycosynthase-like mutant of Mucor hiemalis endo-β-N-acetylglucosaminidase (Endo-M) and sialo-oligosaccharide oxazoline as a donor substrate. 29175660 4 1 theme higher 821:826 arg1 activity 828:835 slightly higher activity 812:835 slightly higher activity than native glucagon 812:856 The synthetic glucagon showed slightly higher activity than native glucagon and has potential as a therapeutic agent for treating diabetic patients. 29175660 3 2 theme high 655:658 arg1 resistance 660:669 high resistance 655:669 high resistance against protease degradation 655:698 The sialo-oligosaccharide-attached glucagon synthesized showed high resistance against protease degradation and stimulated the release of glucose from mouse hepatocytes when added to cells. 29175660 4 3 theme therapeutic 881:891 arg1 agent 893:897 a therapeutic agent 879:897 a therapeutic agent for treating diabetic patients 879:928 The synthetic glucagon showed slightly higher activity than native glucagon and has potential as a therapeutic agent for treating diabetic patients. 29175660 4 3 theme therapeutic 881:891 arg1 potential 866:874 potential 866:874 potential 866:874 The synthetic glucagon showed slightly higher activity than native glucagon and has potential as a therapeutic agent for treating diabetic patients. 29175660 2 4 theme chemical 306:313 arg1 synthesis 315:323 chemical synthesis 306:323 chemical synthesis of an N-acetylglucosaminyl peptide 306:358 We synthesized the glycosylated glucagon by chemical synthesis of an N-acetylglucosaminyl peptide and enzymatic transfer of an oligosaccharide using the transglycosylation activity of the glycosynthase-like mutant of Mucor hiemalis endo-β-N-acetylglucosaminidase (Endo-M) and sialo-oligosaccharide oxazoline as a donor substrate. 29175660 1 5 theme peptide 194:200 arg1 derivative 168:177 an artificially N-glycosylated derivative 137:177 an artificially N-glycosylated derivative of glucagon 137:189 The chemo-enzymatic synthesis of an artificially N-glycosylated derivative of glucagon, a peptide hormone that regulates the blood sugar level, is described. 29175660 1 5 theme peptide 194:200 arg1 hormone 202:208 a peptide hormone 192:208 a peptide hormone that regulates the blood sugar level 192:245 The chemo-enzymatic synthesis of an artificially N-glycosylated derivative of glucagon, a peptide hormone that regulates the blood sugar level, is described. 29175660 0 6 theme N-linked 53:60 arg1 oligosaccharide 62:76 N-linked oligosaccharide 53:76 N-linked oligosaccharide 53:76 Chemo-enzymatic synthesis of the glucagon containing N-linked oligosaccharide and its characterization. 29175660 0 7 theme Chemo-enzymatic 0:14 arg1 synthesis 16:24 Chemo-enzymatic synthesis 0:24 Chemo-enzymatic synthesis of the glucagon 0:40 Chemo-enzymatic synthesis of the glucagon containing N-linked oligosaccharide and its characterization. 29175660 0 8 link N-linked 53:60 arg1 oligosaccharide 62:76 N-linked oligosaccharide 53:76 N-linked oligosaccharide 53:76 Chemo-enzymatic synthesis of the glucagon containing N-linked oligosaccharide and its characterization. 29175660 2 9 theme peptide 352:358 arg1 transfer 374:381 enzymatic transfer 364:381 enzymatic transfer of an oligosaccharide using the transglycosylation activity of the glycosynthase-like mutant of Mucor hiemalis endo-β-N-acetylglucosaminidase (Endo-M) and sialo-oligosaccharide oxazoline as a donor substrate 364:589 We synthesized the glycosylated glucagon by chemical synthesis of an N-acetylglucosaminyl peptide and enzymatic transfer of an oligosaccharide using the transglycosylation activity of the glycosynthase-like mutant of Mucor hiemalis endo-β-N-acetylglucosaminidase (Endo-M) and sialo-oligosaccharide oxazoline as a donor substrate. 29175660 2 9 theme peptide 352:358 arg1 synthesis 315:323 chemical synthesis 306:323 chemical synthesis of an N-acetylglucosaminyl peptide 306:358 We synthesized the glycosylated glucagon by chemical synthesis of an N-acetylglucosaminyl peptide and enzymatic transfer of an oligosaccharide using the transglycosylation activity of the glycosynthase-like mutant of Mucor hiemalis endo-β-N-acetylglucosaminidase (Endo-M) and sialo-oligosaccharide oxazoline as a donor substrate. 29175660 3 10 from hepatocytes 749:759 arg1 release 719:725 the release 715:725 the release of glucose from mouse hepatocytes 715:759 The sialo-oligosaccharide-attached glucagon synthesized showed high resistance against protease degradation and stimulated the release of glucose from mouse hepatocytes when added to cells. 29175660 2 11 gly glycosylated 281:292 arg1 glucagon 294:301 the glycosylated glucagon 277:301 the glycosylated glucagon 277:301 We synthesized the glycosylated glucagon by chemical synthesis of an N-acetylglucosaminyl peptide and enzymatic transfer of an oligosaccharide using the transglycosylation activity of the glycosynthase-like mutant of Mucor hiemalis endo-β-N-acetylglucosaminidase (Endo-M) and sialo-oligosaccharide oxazoline as a donor substrate. 29175660 1 12 theme chemo-enzymatic 108:122 arg1 synthesis 124:132 The chemo-enzymatic synthesis 104:132 The chemo-enzymatic synthesis of an artificially N-glycosylated derivative of glucagon, a peptide hormone that regulates the blood sugar level, 104:246 The chemo-enzymatic synthesis of an artificially N-glycosylated derivative of glucagon, a peptide hormone that regulates the blood sugar level, is described. 29175660 2 13 theme transglycosylation 415:432 arg1 substrate 581:589 a donor substrate 573:589 a donor substrate 573:589 We synthesized the glycosylated glucagon by chemical synthesis of an N-acetylglucosaminyl peptide and enzymatic transfer of an oligosaccharide using the transglycosylation activity of the glycosynthase-like mutant of Mucor hiemalis endo-β-N-acetylglucosaminidase (Endo-M) and sialo-oligosaccharide oxazoline as a donor substrate. 29175660 2 13 theme transglycosylation 415:432 arg1 activity 434:441 the transglycosylation activity 411:441 the transglycosylation activity of the glycosynthase-like mutant of Mucor hiemalis endo-β-N-acetylglucosaminidase (Endo-M) and sialo-oligosaccharide oxazoline 411:568 We synthesized the glycosylated glucagon by chemical synthesis of an N-acetylglucosaminyl peptide and enzymatic transfer of an oligosaccharide using the transglycosylation activity of the glycosynthase-like mutant of Mucor hiemalis endo-β-N-acetylglucosaminidase (Endo-M) and sialo-oligosaccharide oxazoline as a donor substrate. 29175660 2 14 theme endo-β-N-acetylglucosaminidase 494:523 arg1 mutant 469:474 the glycosynthase-like mutant 446:474 the glycosynthase-like mutant of Mucor hiemalis endo-β-N-acetylglucosaminidase (Endo-M) and sialo-oligosaccharide oxazoline 446:568 We synthesized the glycosylated glucagon by chemical synthesis of an N-acetylglucosaminyl peptide and enzymatic transfer of an oligosaccharide using the transglycosylation activity of the glycosynthase-like mutant of Mucor hiemalis endo-β-N-acetylglucosaminidase (Endo-M) and sialo-oligosaccharide oxazoline as a donor substrate. 29175660 2 15 theme Mucor 479:483 arg1 Endo-M 526:531 Endo-M 526:531 Endo-M 526:531 We synthesized the glycosylated glucagon by chemical synthesis of an N-acetylglucosaminyl peptide and enzymatic transfer of an oligosaccharide using the transglycosylation activity of the glycosynthase-like mutant of Mucor hiemalis endo-β-N-acetylglucosaminidase (Endo-M) and sialo-oligosaccharide oxazoline as a donor substrate. 29175660 2 15 theme Mucor 479:483 arg1 endo-β-N-acetylglucosaminidase 494:523 Mucor hiemalis endo-β-N-acetylglucosaminidase 479:523 Mucor hiemalis endo-β-N-acetylglucosaminidase (Endo-M) 479:532 We synthesized the glycosylated glucagon by chemical synthesis of an N-acetylglucosaminyl peptide and enzymatic transfer of an oligosaccharide using the transglycosylation activity of the glycosynthase-like mutant of Mucor hiemalis endo-β-N-acetylglucosaminidase (Endo-M) and sialo-oligosaccharide oxazoline as a donor substrate. 29175660 2 16 theme hiemalis 485:492 arg1 Endo-M 526:531 Endo-M 526:531 Endo-M 526:531 We synthesized the glycosylated glucagon by chemical synthesis of an N-acetylglucosaminyl peptide and enzymatic transfer of an oligosaccharide using the transglycosylation activity of the glycosynthase-like mutant of Mucor hiemalis endo-β-N-acetylglucosaminidase (Endo-M) and sialo-oligosaccharide oxazoline as a donor substrate. 29175660 2 16 theme hiemalis 485:492 arg1 endo-β-N-acetylglucosaminidase 494:523 Mucor hiemalis endo-β-N-acetylglucosaminidase 479:523 Mucor hiemalis endo-β-N-acetylglucosaminidase (Endo-M) 479:532 We synthesized the glycosylated glucagon by chemical synthesis of an N-acetylglucosaminyl peptide and enzymatic transfer of an oligosaccharide using the transglycosylation activity of the glycosynthase-like mutant of Mucor hiemalis endo-β-N-acetylglucosaminidase (Endo-M) and sialo-oligosaccharide oxazoline as a donor substrate. 29175660 4 17 contain has 862:864 arg2 agent 893:897 a therapeutic agent 879:897 a therapeutic agent for treating diabetic patients 879:928 The synthetic glucagon showed slightly higher activity than native glucagon and has potential as a therapeutic agent for treating diabetic patients. 29175660 4 17 contain has 862:864 arg2 potential 866:874 potential 866:874 potential 866:874 The synthetic glucagon showed slightly higher activity than native glucagon and has potential as a therapeutic agent for treating diabetic patients. 29175660 4 17 contain has 862:864 arg1 glucagon 796:803 The synthetic glucagon 782:803 The synthetic glucagon 782:803 The synthetic glucagon showed slightly higher activity than native glucagon and has potential as a therapeutic agent for treating diabetic patients. 29175660 3 18 theme protease 679:686 arg1 degradation 688:698 protease degradation 679:698 protease degradation 679:698 The sialo-oligosaccharide-attached glucagon synthesized showed high resistance against protease degradation and stimulated the release of glucose from mouse hepatocytes when added to cells. 29175660 1 19 theme blood 229:233 arg1 level 241:245 the blood sugar level 225:245 the blood sugar level 225:245 The chemo-enzymatic synthesis of an artificially N-glycosylated derivative of glucagon, a peptide hormone that regulates the blood sugar level, is described. 29175660 2 20 theme oxazoline 560:568 arg1 mutant 469:474 the glycosynthase-like mutant 446:474 the glycosynthase-like mutant of Mucor hiemalis endo-β-N-acetylglucosaminidase (Endo-M) and sialo-oligosaccharide oxazoline 446:568 We synthesized the glycosylated glucagon by chemical synthesis of an N-acetylglucosaminyl peptide and enzymatic transfer of an oligosaccharide using the transglycosylation activity of the glycosynthase-like mutant of Mucor hiemalis endo-β-N-acetylglucosaminidase (Endo-M) and sialo-oligosaccharide oxazoline as a donor substrate. 29175660 1 21 theme sugar 235:239 arg1 level 241:245 the blood sugar level 225:245 the blood sugar level 225:245 The chemo-enzymatic synthesis of an artificially N-glycosylated derivative of glucagon, a peptide hormone that regulates the blood sugar level, is described. 29175660 4 22 theme synthetic 786:794 arg1 glucagon 796:803 The synthetic glucagon 782:803 The synthetic glucagon 782:803 The synthetic glucagon showed slightly higher activity than native glucagon and has potential as a therapeutic agent for treating diabetic patients. 29175660 2 23 theme mutant 469:474 arg1 substrate 581:589 a donor substrate 573:589 a donor substrate 573:589 We synthesized the glycosylated glucagon by chemical synthesis of an N-acetylglucosaminyl peptide and enzymatic transfer of an oligosaccharide using the transglycosylation activity of the glycosynthase-like mutant of Mucor hiemalis endo-β-N-acetylglucosaminidase (Endo-M) and sialo-oligosaccharide oxazoline as a donor substrate. 29175660 2 23 theme mutant 469:474 arg1 activity 434:441 the transglycosylation activity 411:441 the transglycosylation activity of the glycosynthase-like mutant of Mucor hiemalis endo-β-N-acetylglucosaminidase (Endo-M) and sialo-oligosaccharide oxazoline 411:568 We synthesized the glycosylated glucagon by chemical synthesis of an N-acetylglucosaminyl peptide and enzymatic transfer of an oligosaccharide using the transglycosylation activity of the glycosynthase-like mutant of Mucor hiemalis endo-β-N-acetylglucosaminidase (Endo-M) and sialo-oligosaccharide oxazoline as a donor substrate. 29175660 2 24 theme sialo-oligosaccharide 538:558 arg1 oxazoline 560:568 sialo-oligosaccharide oxazoline 538:568 sialo-oligosaccharide oxazoline 538:568 We synthesized the glycosylated glucagon by chemical synthesis of an N-acetylglucosaminyl peptide and enzymatic transfer of an oligosaccharide using the transglycosylation activity of the glycosynthase-like mutant of Mucor hiemalis endo-β-N-acetylglucosaminidase (Endo-M) and sialo-oligosaccharide oxazoline as a donor substrate. 29175660 0 25 theme glucagon 33:40 arg1 synthesis 16:24 Chemo-enzymatic synthesis 0:24 Chemo-enzymatic synthesis of the glucagon 0:40 Chemo-enzymatic synthesis of the glucagon containing N-linked oligosaccharide and its characterization. 29175660 2 26 theme glycosynthase-like 450:467 arg1 mutant 469:474 the glycosynthase-like mutant 446:474 the glycosynthase-like mutant of Mucor hiemalis endo-β-N-acetylglucosaminidase (Endo-M) and sialo-oligosaccharide oxazoline 446:568 We synthesized the glycosylated glucagon by chemical synthesis of an N-acetylglucosaminyl peptide and enzymatic transfer of an oligosaccharide using the transglycosylation activity of the glycosynthase-like mutant of Mucor hiemalis endo-β-N-acetylglucosaminidase (Endo-M) and sialo-oligosaccharide oxazoline as a donor substrate. 29175660 2 27 theme N-acetylglucosaminyl 331:350 arg1 peptide 352:358 an N-acetylglucosaminyl peptide 328:358 an N-acetylglucosaminyl peptide 328:358 We synthesized the glycosylated glucagon by chemical synthesis of an N-acetylglucosaminyl peptide and enzymatic transfer of an oligosaccharide using the transglycosylation activity of the glycosynthase-like mutant of Mucor hiemalis endo-β-N-acetylglucosaminidase (Endo-M) and sialo-oligosaccharide oxazoline as a donor substrate. 29175660 4 28 theme native 842:847 arg1 glucagon 849:856 native glucagon 842:856 native glucagon 842:856 The synthetic glucagon showed slightly higher activity than native glucagon and has potential as a therapeutic agent for treating diabetic patients. 29175660 1 29 gly N-glycosylated 153:166 arg1 derivative 168:177 an artificially N-glycosylated derivative 137:177 an artificially N-glycosylated derivative of glucagon 137:189 The chemo-enzymatic synthesis of an artificially N-glycosylated derivative of glucagon, a peptide hormone that regulates the blood sugar level, is described. 29175660 1 29 gly N-glycosylated 153:166 arg1 hormone 202:208 a peptide hormone 192:208 a peptide hormone that regulates the blood sugar level 192:245 The chemo-enzymatic synthesis of an artificially N-glycosylated derivative of glucagon, a peptide hormone that regulates the blood sugar level, is described. 29175660 3 30 theme mouse 743:747 arg1 hepatocytes 749:759 mouse hepatocytes 743:759 mouse hepatocytes 743:759 The sialo-oligosaccharide-attached glucagon synthesized showed high resistance against protease degradation and stimulated the release of glucose from mouse hepatocytes when added to cells. 29175660 2 31 theme glycosylated 281:292 arg1 glucagon 294:301 the glycosylated glucagon 277:301 the glycosylated glucagon 277:301 We synthesized the glycosylated glucagon by chemical synthesis of an N-acetylglucosaminyl peptide and enzymatic transfer of an oligosaccharide using the transglycosylation activity of the glycosynthase-like mutant of Mucor hiemalis endo-β-N-acetylglucosaminidase (Endo-M) and sialo-oligosaccharide oxazoline as a donor substrate. 29175660 1 32 theme N-glycosylated 153:166 arg1 derivative 168:177 an artificially N-glycosylated derivative 137:177 an artificially N-glycosylated derivative of glucagon 137:189 The chemo-enzymatic synthesis of an artificially N-glycosylated derivative of glucagon, a peptide hormone that regulates the blood sugar level, is described. 29175660 1 32 theme N-glycosylated 153:166 arg1 hormone 202:208 a peptide hormone 192:208 a peptide hormone that regulates the blood sugar level 192:245 The chemo-enzymatic synthesis of an artificially N-glycosylated derivative of glucagon, a peptide hormone that regulates the blood sugar level, is described. 29175660 4 33 theme diabetic 912:919 arg1 patients 921:928 diabetic patients 912:928 diabetic patients 912:928 The synthetic glucagon showed slightly higher activity than native glucagon and has potential as a therapeutic agent for treating diabetic patients. 29175660 1 34 theme derivative 168:177 arg1 synthesis 124:132 The chemo-enzymatic synthesis 104:132 The chemo-enzymatic synthesis of an artificially N-glycosylated derivative of glucagon, a peptide hormone that regulates the blood sugar level, 104:246 The chemo-enzymatic synthesis of an artificially N-glycosylated derivative of glucagon, a peptide hormone that regulates the blood sugar level, is described. 29175660 2 35 theme enzymatic 364:372 arg1 transfer 374:381 enzymatic transfer 364:381 enzymatic transfer of an oligosaccharide using the transglycosylation activity of the glycosynthase-like mutant of Mucor hiemalis endo-β-N-acetylglucosaminidase (Endo-M) and sialo-oligosaccharide oxazoline as a donor substrate 364:589 We synthesized the glycosylated glucagon by chemical synthesis of an N-acetylglucosaminyl peptide and enzymatic transfer of an oligosaccharide using the transglycosylation activity of the glycosynthase-like mutant of Mucor hiemalis endo-β-N-acetylglucosaminidase (Endo-M) and sialo-oligosaccharide oxazoline as a donor substrate. 29175660 3 36 theme glucose 730:736 arg1 release 719:725 the release 715:725 the release of glucose from mouse hepatocytes 715:759 The sialo-oligosaccharide-attached glucagon synthesized showed high resistance against protease degradation and stimulated the release of glucose from mouse hepatocytes when added to cells. 29175660 3 37 theme sialo-oligosaccharide-attached 596:625 arg1 glucagon 627:634 The sialo-oligosaccharide-attached glucagon 592:634 The sialo-oligosaccharide-attached glucagon synthesized 592:646 The sialo-oligosaccharide-attached glucagon synthesized showed high resistance against protease degradation and stimulated the release of glucose from mouse hepatocytes when added to cells. 29175660 2 38 theme donor 575:579 arg1 substrate 581:589 a donor substrate 573:589 a donor substrate 573:589 We synthesized the glycosylated glucagon by chemical synthesis of an N-acetylglucosaminyl peptide and enzymatic transfer of an oligosaccharide using the transglycosylation activity of the glycosynthase-like mutant of Mucor hiemalis endo-β-N-acetylglucosaminidase (Endo-M) and sialo-oligosaccharide oxazoline as a donor substrate. 29175660 2 38 theme donor 575:579 arg1 activity 434:441 the transglycosylation activity 411:441 the transglycosylation activity of the glycosynthase-like mutant of Mucor hiemalis endo-β-N-acetylglucosaminidase (Endo-M) and sialo-oligosaccharide oxazoline 411:568 We synthesized the glycosylated glucagon by chemical synthesis of an N-acetylglucosaminyl peptide and enzymatic transfer of an oligosaccharide using the transglycosylation activity of the glycosynthase-like mutant of Mucor hiemalis endo-β-N-acetylglucosaminidase (Endo-M) and sialo-oligosaccharide oxazoline as a donor substrate. 29175660 1 39 theme glucagon 182:189 arg1 derivative 168:177 an artificially N-glycosylated derivative 137:177 an artificially N-glycosylated derivative of glucagon 137:189 The chemo-enzymatic synthesis of an artificially N-glycosylated derivative of glucagon, a peptide hormone that regulates the blood sugar level, is described. 29175660 1 39 theme glucagon 182:189 arg1 hormone 202:208 a peptide hormone 192:208 a peptide hormone that regulates the blood sugar level 192:245 The chemo-enzymatic synthesis of an artificially N-glycosylated derivative of glucagon, a peptide hormone that regulates the blood sugar level, is described. 28511558 0 0 theme paniculata 64:73 arg1 roots 47:51 the roots 43:51 the roots of Murraya paniculata 43:73 Three new indole alkaloid derivatives from the roots of Murraya paniculata. 28511558 4 1 theme derivatives 608:618 arg1 heterodimer 562:572 the first heterodimer 552:572 the first heterodimer of C-N linked indole and coumarin derivatives 552:618 Compound 3 is the first heterodimer of C-N linked indole and coumarin derivatives. 28511558 4 1 theme derivatives 608:618 arg1 Compound 538:545 Compound 3 538:547 Compound 3 538:547 Compound 3 is the first heterodimer of C-N linked indole and coumarin derivatives. 28511558 3 2 theme specific 477:484 arg1 rotation 494:501 specific optical rotation 477:501 specific optical rotation 477:501 The absolute configurations of new compounds were assigned via the determination of specific optical rotation, Mosher's method, and ECD spectra. 28511558 1 3 theme Murraya 206:212 arg1 paniculata 214:223 Murraya paniculata 206:223 Murraya paniculata 206:223 Three new indole alkaloid derivatives, named paniculidines D‒F (1‒3), and six known analogs (4‒9) were isolated from the roots of Murraya paniculata. 28511558 0 4 from roots 47:51 arg1 derivatives 26:36 Three new indole alkaloid derivatives 0:36 Three new indole alkaloid derivatives from the roots of Murraya paniculata. 0:74 Three new indole alkaloid derivatives from the roots of Murraya paniculata. 28511558 3 5 theme optical 486:492 arg1 rotation 494:501 specific optical rotation 477:501 specific optical rotation 477:501 The absolute configurations of new compounds were assigned via the determination of specific optical rotation, Mosher's method, and ECD spectra. 28511558 1 6 theme paniculata 214:223 arg1 roots 197:201 the roots 193:201 the roots of Murraya paniculata 193:223 Three new indole alkaloid derivatives, named paniculidines D‒F (1‒3), and six known analogs (4‒9) were isolated from the roots of Murraya paniculata. 28511558 2 7 with analysis 331:338 arg1 data 364:367 the data 360:367 the data reported in literature 360:390 The structures were elucidated on the basis of comprehensive HRESIMS, UV, IR, and NMR spectroscopic data analysis and comparison with the data reported in literature. 28511558 4 8 theme indole 588:593 arg1 derivatives 608:618 C-N linked indole and coumarin derivatives 577:618 C-N linked indole and coumarin derivatives 577:618 Compound 3 is the first heterodimer of C-N linked indole and coumarin derivatives. 28511558 2 9 theme spectroscopic 312:324 arg1 HRESIMS 287:293 comprehensive HRESIMS 273:293 comprehensive HRESIMS 273:293 The structures were elucidated on the basis of comprehensive HRESIMS, UV, IR, and NMR spectroscopic data analysis and comparison with the data reported in literature. 28511558 2 9 theme spectroscopic 312:324 arg1 data 326:329 NMR spectroscopic data 308:329 NMR spectroscopic data analysis and comparison with the data reported in literature 308:390 The structures were elucidated on the basis of comprehensive HRESIMS, UV, IR, and NMR spectroscopic data analysis and comparison with the data reported in literature. 28511558 2 9 theme spectroscopic 312:324 arg1 comparison 344:353 comparison 344:353 comparison with the data reported in literature 344:390 The structures were elucidated on the basis of comprehensive HRESIMS, UV, IR, and NMR spectroscopic data analysis and comparison with the data reported in literature. 28511558 2 9 theme spectroscopic 312:324 arg1 analysis 331:338 analysis 331:338 analysis 331:338 The structures were elucidated on the basis of comprehensive HRESIMS, UV, IR, and NMR spectroscopic data analysis and comparison with the data reported in literature. 28511558 0 10 theme new 6:8 arg1 derivatives 26:36 Three new indole alkaloid derivatives 0:36 Three new indole alkaloid derivatives from the roots of Murraya paniculata. 0:74 Three new indole alkaloid derivatives from the roots of Murraya paniculata. 28511558 2 11 with comparison 344:353 arg1 data 364:367 the data 360:367 the data reported in literature 360:390 The structures were elucidated on the basis of comprehensive HRESIMS, UV, IR, and NMR spectroscopic data analysis and comparison with the data reported in literature. 28511558 2 12 theme NMR 308:310 arg1 HRESIMS 287:293 comprehensive HRESIMS 273:293 comprehensive HRESIMS 273:293 The structures were elucidated on the basis of comprehensive HRESIMS, UV, IR, and NMR spectroscopic data analysis and comparison with the data reported in literature. 28511558 2 12 theme NMR 308:310 arg1 data 326:329 NMR spectroscopic data 308:329 NMR spectroscopic data analysis and comparison with the data reported in literature 308:390 The structures were elucidated on the basis of comprehensive HRESIMS, UV, IR, and NMR spectroscopic data analysis and comparison with the data reported in literature. 28511558 2 12 theme NMR 308:310 arg1 comparison 344:353 comparison 344:353 comparison with the data reported in literature 344:390 The structures were elucidated on the basis of comprehensive HRESIMS, UV, IR, and NMR spectroscopic data analysis and comparison with the data reported in literature. 28511558 2 12 theme NMR 308:310 arg1 analysis 331:338 analysis 331:338 analysis 331:338 The structures were elucidated on the basis of comprehensive HRESIMS, UV, IR, and NMR spectroscopic data analysis and comparison with the data reported in literature. 28511558 1 13 theme new 82:84 arg1 derivatives 102:112 Three new indole alkaloid derivatives 76:112 Three new indole alkaloid derivatives 76:112 Three new indole alkaloid derivatives, named paniculidines D‒F (1‒3), and six known analogs (4‒9) were isolated from the roots of Murraya paniculata. 28511558 1 14 theme known 154:158 arg1 4‒9 169:171 4‒9 169:171 4‒9 169:171 Three new indole alkaloid derivatives, named paniculidines D‒F (1‒3), and six known analogs (4‒9) were isolated from the roots of Murraya paniculata. 28511558 1 14 theme known 154:158 arg1 analogs 160:166 six known analogs 150:166 six known analogs (4‒9) 150:172 Three new indole alkaloid derivatives, named paniculidines D‒F (1‒3), and six known analogs (4‒9) were isolated from the roots of Murraya paniculata. 28511558 0 15 theme alkaloid 17:24 arg1 derivatives 26:36 Three new indole alkaloid derivatives 0:36 Three new indole alkaloid derivatives from the roots of Murraya paniculata. 0:74 Three new indole alkaloid derivatives from the roots of Murraya paniculata. 28511558 1 16 theme indole 86:91 arg1 derivatives 102:112 Three new indole alkaloid derivatives 76:112 Three new indole alkaloid derivatives 76:112 Three new indole alkaloid derivatives, named paniculidines D‒F (1‒3), and six known analogs (4‒9) were isolated from the roots of Murraya paniculata. 28511558 0 17 theme indole 10:15 arg1 derivatives 26:36 Three new indole alkaloid derivatives 0:36 Three new indole alkaloid derivatives from the roots of Murraya paniculata. 0:74 Three new indole alkaloid derivatives from the roots of Murraya paniculata. 28511558 1 18 theme alkaloid 93:100 arg1 derivatives 102:112 Three new indole alkaloid derivatives 76:112 Three new indole alkaloid derivatives 76:112 Three new indole alkaloid derivatives, named paniculidines D‒F (1‒3), and six known analogs (4‒9) were isolated from the roots of Murraya paniculata. 28511558 3 19 theme absolute 397:404 arg1 configurations 406:419 The absolute configurations 393:419 The absolute configurations of new compounds 393:436 The absolute configurations of new compounds were assigned via the determination of specific optical rotation, Mosher's method, and ECD spectra. 28511558 3 20 theme compounds 428:436 arg1 configurations 406:419 The absolute configurations 393:419 The absolute configurations of new compounds 393:436 The absolute configurations of new compounds were assigned via the determination of specific optical rotation, Mosher's method, and ECD spectra. 28511558 1 21 attach isolated 179:186 arg2 4‒9 169:171 4‒9 169:171 4‒9 169:171 Three new indole alkaloid derivatives, named paniculidines D‒F (1‒3), and six known analogs (4‒9) were isolated from the roots of Murraya paniculata. 28511558 1 21 attach isolated 179:186 arg2 derivatives 102:112 Three new indole alkaloid derivatives 76:112 Three new indole alkaloid derivatives 76:112 Three new indole alkaloid derivatives, named paniculidines D‒F (1‒3), and six known analogs (4‒9) were isolated from the roots of Murraya paniculata. 28511558 1 21 attach isolated 179:186 arg2 D‒F 135:137 named paniculidines D‒F 115:137 named paniculidines D‒F (1‒3) 115:143 Three new indole alkaloid derivatives, named paniculidines D‒F (1‒3), and six known analogs (4‒9) were isolated from the roots of Murraya paniculata. 28511558 1 21 attach isolated 179:186 arg1 roots 197:201 the roots 193:201 the roots of Murraya paniculata 193:223 Three new indole alkaloid derivatives, named paniculidines D‒F (1‒3), and six known analogs (4‒9) were isolated from the roots of Murraya paniculata. 28511558 1 21 attach isolated 179:186 arg2 1‒3 140:142 1‒3 140:142 1‒3 140:142 Three new indole alkaloid derivatives, named paniculidines D‒F (1‒3), and six known analogs (4‒9) were isolated from the roots of Murraya paniculata. 28511558 1 21 attach isolated 179:186 arg2 analogs 160:166 six known analogs 150:166 six known analogs (4‒9) 150:172 Three new indole alkaloid derivatives, named paniculidines D‒F (1‒3), and six known analogs (4‒9) were isolated from the roots of Murraya paniculata. 28511558 4 22 theme linked 581:586 arg1 derivatives 608:618 C-N linked indole and coumarin derivatives 577:618 C-N linked indole and coumarin derivatives 577:618 Compound 3 is the first heterodimer of C-N linked indole and coumarin derivatives. 28511558 3 23 theme ECD 525:527 arg1 spectra 529:535 ECD spectra 525:535 ECD spectra 525:535 The absolute configurations of new compounds were assigned via the determination of specific optical rotation, Mosher's method, and ECD spectra. 28511558 4 24 theme first 556:560 arg1 heterodimer 562:572 the first heterodimer 552:572 the first heterodimer of C-N linked indole and coumarin derivatives 552:618 Compound 3 is the first heterodimer of C-N linked indole and coumarin derivatives. 28511558 4 24 theme first 556:560 arg1 Compound 538:545 Compound 3 538:547 Compound 3 538:547 Compound 3 is the first heterodimer of C-N linked indole and coumarin derivatives. 28511558 3 25 theme new 424:426 arg1 compounds 428:436 new compounds 424:436 new compounds 424:436 The absolute configurations of new compounds were assigned via the determination of specific optical rotation, Mosher's method, and ECD spectra. 28511558 2 26 theme HRESIMS 287:293 arg1 basis 264:268 the basis 260:268 the basis of comprehensive HRESIMS, UV, IR, and NMR spectroscopic data analysis and comparison with the data reported in literature 260:390 The structures were elucidated on the basis of comprehensive HRESIMS, UV, IR, and NMR spectroscopic data analysis and comparison with the data reported in literature. 28511558 4 27 link linked 581:586 arg1 derivatives 608:618 C-N linked indole and coumarin derivatives 577:618 C-N linked indole and coumarin derivatives 577:618 Compound 3 is the first heterodimer of C-N linked indole and coumarin derivatives. 28511558 1 28 theme named 115:119 arg1 1‒3 140:142 1‒3 140:142 1‒3 140:142 Three new indole alkaloid derivatives, named paniculidines D‒F (1‒3), and six known analogs (4‒9) were isolated from the roots of Murraya paniculata. 28511558 1 28 theme named 115:119 arg1 D‒F 135:137 named paniculidines D‒F 115:137 named paniculidines D‒F (1‒3) 115:143 Three new indole alkaloid derivatives, named paniculidines D‒F (1‒3), and six known analogs (4‒9) were isolated from the roots of Murraya paniculata. 28511558 3 29 theme rotation 494:501 arg1 determination 460:472 the determination 456:472 the determination of specific optical rotation, Mosher's method, and ECD spectra 456:535 The absolute configurations of new compounds were assigned via the determination of specific optical rotation, Mosher's method, and ECD spectra. 28511558 4 30 dep linked 581:586 arg1 C-N 577:579 C-N 577:579 C-N 577:579 Compound 3 is the first heterodimer of C-N linked indole and coumarin derivatives. 28511558 1 31 theme paniculidines 121:133 arg1 1‒3 140:142 1‒3 140:142 1‒3 140:142 Three new indole alkaloid derivatives, named paniculidines D‒F (1‒3), and six known analogs (4‒9) were isolated from the roots of Murraya paniculata. 28511558 1 31 theme paniculidines 121:133 arg1 D‒F 135:137 named paniculidines D‒F 115:137 named paniculidines D‒F (1‒3) 115:143 Three new indole alkaloid derivatives, named paniculidines D‒F (1‒3), and six known analogs (4‒9) were isolated from the roots of Murraya paniculata. 28511558 2 32 theme comprehensive 273:285 arg1 HRESIMS 287:293 comprehensive HRESIMS 273:293 comprehensive HRESIMS 273:293 The structures were elucidated on the basis of comprehensive HRESIMS, UV, IR, and NMR spectroscopic data analysis and comparison with the data reported in literature. 28511558 2 32 theme comprehensive 273:285 arg1 data 326:329 NMR spectroscopic data 308:329 NMR spectroscopic data analysis and comparison with the data reported in literature 308:390 The structures were elucidated on the basis of comprehensive HRESIMS, UV, IR, and NMR spectroscopic data analysis and comparison with the data reported in literature. 28511558 2 32 theme comprehensive 273:285 arg1 IR 300:301 IR 300:301 IR 300:301 The structures were elucidated on the basis of comprehensive HRESIMS, UV, IR, and NMR spectroscopic data analysis and comparison with the data reported in literature. 28511558 2 32 theme comprehensive 273:285 arg1 UV 296:297 UV 296:297 UV 296:297 The structures were elucidated on the basis of comprehensive HRESIMS, UV, IR, and NMR spectroscopic data analysis and comparison with the data reported in literature. 28511558 0 33 theme Murraya 56:62 arg1 paniculata 64:73 Murraya paniculata 56:73 Murraya paniculata 56:73 Three new indole alkaloid derivatives from the roots of Murraya paniculata. 28511558 2 34 dep data 326:329 arg1 data 326:329 NMR spectroscopic data 308:329 NMR spectroscopic data analysis and comparison with the data reported in literature 308:390 The structures were elucidated on the basis of comprehensive HRESIMS, UV, IR, and NMR spectroscopic data analysis and comparison with the data reported in literature. 28511558 2 34 dep data 326:329 arg1 comparison 344:353 comparison 344:353 comparison with the data reported in literature 344:390 The structures were elucidated on the basis of comprehensive HRESIMS, UV, IR, and NMR spectroscopic data analysis and comparison with the data reported in literature. 28511558 2 34 dep data 326:329 arg1 analysis 331:338 analysis 331:338 analysis 331:338 The structures were elucidated on the basis of comprehensive HRESIMS, UV, IR, and NMR spectroscopic data analysis and comparison with the data reported in literature. 28511558 4 35 theme coumarin 599:606 arg1 derivatives 608:618 C-N linked indole and coumarin derivatives 577:618 C-N linked indole and coumarin derivatives 577:618 Compound 3 is the first heterodimer of C-N linked indole and coumarin derivatives. 27737617 6 0 link N-linked 782:789 arg1 oligosaccharides 791:806 complex N-linked oligosaccharides 774:806 complex N-linked oligosaccharides 774:806 The results of a glycosidase reaction suggested that FfIBP possesses complex N-linked oligosaccharides. 27737617 8 1 theme active 991:996 arg1 proteins 1009:1016 highly active antifreeze proteins 984:1016 highly active antifreeze proteins 984:1016 The findings of this study could be utilized to produce highly active antifreeze proteins on a large scale. 27737617 7 2 theme site 870:873 arg1 site 870:873 the glycosylated site 853:873 the glycosylated site 853:873 These results indicate that the residues of the glycosylated site could disturb the binding of FfIBP to ice molecules. 27737617 7 2 theme site 870:873 arg1 residues 841:848 the residues 837:848 the residues of the glycosylated site 837:873 These results indicate that the residues of the glycosylated site could disturb the binding of FfIBP to ice molecules. 27737617 3 3 from PS1 387:389 arg1 IBP 354:356 an IBP 351:356 an IBP from Flavobacterium frigoris PS1 351:389 Recently, a recombinant FfIBP (an IBP from Flavobacterium frigoris PS1) was cloned and produced in Pichia pastoris using fed-batch fermentation with methanol feeding. 27737617 3 3 from PS1 387:389 arg1 FfIBP 344:348 a recombinant FfIBP 330:348 a recombinant FfIBP (an IBP from Flavobacterium frigoris PS1) 330:390 Recently, a recombinant FfIBP (an IBP from Flavobacterium frigoris PS1) was cloned and produced in Pichia pastoris using fed-batch fermentation with methanol feeding. 27737617 4 4 gly glycosylation 558:570 arg2 site 572:575 a glycosylation site 556:575 a glycosylation site 556:575 In this study, we demonstrate that FfIBP produced by P. pastoris has a glycosylation site, which diminishes the thermal hysteresis activity of FfIBP. 27737617 1 5 theme polar 161:165 arg1 organisms 167:175 polar organisms 161:175 polar organisms 161:175 To survive in a subzero environment, polar organisms produce ice-binding proteins (IBPs). 27737617 3 6 theme recombinant 332:342 arg1 IBP 354:356 an IBP 351:356 an IBP from Flavobacterium frigoris PS1 351:389 Recently, a recombinant FfIBP (an IBP from Flavobacterium frigoris PS1) was cloned and produced in Pichia pastoris using fed-batch fermentation with methanol feeding. 27737617 3 6 theme recombinant 332:342 arg1 FfIBP 344:348 a recombinant FfIBP 330:348 a recombinant FfIBP (an IBP from Flavobacterium frigoris PS1) 330:390 Recently, a recombinant FfIBP (an IBP from Flavobacterium frigoris PS1) was cloned and produced in Pichia pastoris using fed-batch fermentation with methanol feeding. 27737617 6 7 theme complex 774:780 arg1 oligosaccharides 791:806 complex N-linked oligosaccharides 774:806 complex N-linked oligosaccharides 774:806 The results of a glycosidase reaction suggested that FfIBP possesses complex N-linked oligosaccharides. 27737617 8 8 theme antifreeze 998:1007 arg1 proteins 1009:1016 highly active antifreeze proteins 984:1016 highly active antifreeze proteins 984:1016 The findings of this study could be utilized to produce highly active antifreeze proteins on a large scale. 27737617 8 9 theme study 949:953 arg1 findings 932:939 The findings 928:939 The findings of this study 928:953 The findings of this study could be utilized to produce highly active antifreeze proteins on a large scale. 27737617 2 10 theme crystals 274:281 arg1 fatal 297:301 fatal 297:301 fatal 297:301 These IBPs prevent the formation of large intracellular ice crystals, which may be fatal to the organism. 27737617 2 10 theme crystals 274:281 arg1 formation 237:245 the formation 233:245 the formation 233:245 These IBPs prevent the formation of large intracellular ice crystals, which may be fatal to the organism. 27737617 0 11 theme N-glycosylation 107:121 arg1 removal 96:102 removal 96:102 removal of N-glycosylation 96:121 Improving thermal hysteresis activity of antifreeze protein from recombinant Pichia pastoris by removal of N-glycosylation. 27737617 3 12 with fermentation 451:462 arg1 feeding 478:484 methanol feeding 469:484 methanol feeding 469:484 Recently, a recombinant FfIBP (an IBP from Flavobacterium frigoris PS1) was cloned and produced in Pichia pastoris using fed-batch fermentation with methanol feeding. 27737617 7 13 gly glycosylated 857:868 arg1 site 870:873 the glycosylated site 853:873 the glycosylated site 853:873 These results indicate that the residues of the glycosylated site could disturb the binding of FfIBP to ice molecules. 27737617 2 14 theme ice 270:272 arg1 crystals 274:281 large intracellular ice crystals 250:281 large intracellular ice crystals 250:281 These IBPs prevent the formation of large intracellular ice crystals, which may be fatal to the organism. 27737617 0 15 theme thermal 10:16 arg1 activity 29:36 thermal hysteresis activity 10:36 thermal hysteresis activity of antifreeze protein from recombinant Pichia pastoris 10:91 Improving thermal hysteresis activity of antifreeze protein from recombinant Pichia pastoris by removal of N-glycosylation. 27737617 7 16 theme ice 913:915 arg1 molecules 917:925 ice molecules 913:925 ice molecules 913:925 These results indicate that the residues of the glycosylated site could disturb the binding of FfIBP to ice molecules. 27737617 1 17 theme ice-binding 185:195 arg1 IBPs 207:210 IBPs 207:210 IBPs 207:210 To survive in a subzero environment, polar organisms produce ice-binding proteins (IBPs). 27737617 1 17 theme ice-binding 185:195 arg1 proteins 197:204 ice-binding proteins 185:204 ice-binding proteins (IBPs) 185:211 To survive in a subzero environment, polar organisms produce ice-binding proteins (IBPs). 27737617 8 18 theme large 1023:1027 arg1 scale 1029:1033 a large scale 1021:1033 a large scale 1021:1033 The findings of this study could be utilized to produce highly active antifreeze proteins on a large scale. 27737617 6 19 theme reaction 734:741 arg1 results 709:715 The results 705:715 The results of a glycosidase reaction 705:741 The results of a glycosidase reaction suggested that FfIBP possesses complex N-linked oligosaccharides. 27737617 0 20 theme protein 52:58 arg1 activity 29:36 thermal hysteresis activity 10:36 thermal hysteresis activity of antifreeze protein from recombinant Pichia pastoris 10:91 Improving thermal hysteresis activity of antifreeze protein from recombinant Pichia pastoris by removal of N-glycosylation. 27737617 4 21 theme FfIBP 630:634 arg1 activity 618:625 the thermal hysteresis activity 595:625 the thermal hysteresis activity of FfIBP 595:634 In this study, we demonstrate that FfIBP produced by P. pastoris has a glycosylation site, which diminishes the thermal hysteresis activity of FfIBP. 27737617 5 22 theme P. 660:661 arg1 pastoris 663:670 P. pastoris 660:670 P. pastoris 660:670 The FfIBP expressed by P. pastoris exhibited a doublet on SDS-PAGE. 27737617 6 23 theme glycosidase 722:732 arg1 reaction 734:741 a glycosidase reaction 720:741 a glycosidase reaction 720:741 The results of a glycosidase reaction suggested that FfIBP possesses complex N-linked oligosaccharides. 27737617 6 24 theme N-linked 782:789 arg1 oligosaccharides 791:806 complex N-linked oligosaccharides 774:806 complex N-linked oligosaccharides 774:806 The results of a glycosidase reaction suggested that FfIBP possesses complex N-linked oligosaccharides. 27737617 0 25 theme hysteresis 18:27 arg1 activity 29:36 thermal hysteresis activity 10:36 thermal hysteresis activity of antifreeze protein from recombinant Pichia pastoris 10:91 Improving thermal hysteresis activity of antifreeze protein from recombinant Pichia pastoris by removal of N-glycosylation. 27737617 0 26 theme antifreeze 41:50 arg1 protein 52:58 antifreeze protein 41:58 antifreeze protein from recombinant Pichia pastoris 41:91 Improving thermal hysteresis activity of antifreeze protein from recombinant Pichia pastoris by removal of N-glycosylation. 27737617 0 27 from pastoris 84:91 arg1 activity 29:36 thermal hysteresis activity 10:36 thermal hysteresis activity of antifreeze protein from recombinant Pichia pastoris 10:91 Improving thermal hysteresis activity of antifreeze protein from recombinant Pichia pastoris by removal of N-glycosylation. 27737617 0 27 from pastoris 84:91 arg1 protein 52:58 antifreeze protein 41:58 antifreeze protein from recombinant Pichia pastoris 41:91 Improving thermal hysteresis activity of antifreeze protein from recombinant Pichia pastoris by removal of N-glycosylation. 27737617 4 28 contain has 552:554 arg1 FfIBP 522:526 FfIBP 522:526 FfIBP produced by P. pastoris 522:550 In this study, we demonstrate that FfIBP produced by P. pastoris has a glycosylation site, which diminishes the thermal hysteresis activity of FfIBP. 27737617 4 28 contain has 552:554 arg2 site 572:575 a glycosylation site 556:575 a glycosylation site 556:575 In this study, we demonstrate that FfIBP produced by P. pastoris has a glycosylation site, which diminishes the thermal hysteresis activity of FfIBP. 27737617 8 29 used utilized 964:971 arg2 findings 932:939 The findings 928:939 The findings of this study 928:953 The findings of this study could be utilized to produce highly active antifreeze proteins on a large scale. 27737617 4 30 theme hysteresis 607:616 arg1 activity 618:625 the thermal hysteresis activity 595:625 the thermal hysteresis activity of FfIBP 595:634 In this study, we demonstrate that FfIBP produced by P. pastoris has a glycosylation site, which diminishes the thermal hysteresis activity of FfIBP. 27737617 3 31 theme Pichia 419:424 arg1 pastoris 426:433 Pichia pastoris 419:433 Pichia pastoris 419:433 Recently, a recombinant FfIBP (an IBP from Flavobacterium frigoris PS1) was cloned and produced in Pichia pastoris using fed-batch fermentation with methanol feeding. 27737617 3 32 theme Flavobacterium 363:376 arg1 PS1 387:389 Flavobacterium frigoris PS1 363:389 Flavobacterium frigoris PS1 363:389 Recently, a recombinant FfIBP (an IBP from Flavobacterium frigoris PS1) was cloned and produced in Pichia pastoris using fed-batch fermentation with methanol feeding. 27737617 6 33 contain possesses 764:772 arg2 oligosaccharides 791:806 complex N-linked oligosaccharides 774:806 complex N-linked oligosaccharides 774:806 The results of a glycosidase reaction suggested that FfIBP possesses complex N-linked oligosaccharides. 27737617 6 33 contain possesses 764:772 arg1 FfIBP 758:762 FfIBP 758:762 FfIBP 758:762 The results of a glycosidase reaction suggested that FfIBP possesses complex N-linked oligosaccharides. 27737617 3 34 theme frigoris 378:385 arg1 PS1 387:389 Flavobacterium frigoris PS1 363:389 Flavobacterium frigoris PS1 363:389 Recently, a recombinant FfIBP (an IBP from Flavobacterium frigoris PS1) was cloned and produced in Pichia pastoris using fed-batch fermentation with methanol feeding. 27737617 3 35 theme methanol 469:476 arg1 feeding 478:484 methanol feeding 469:484 methanol feeding 469:484 Recently, a recombinant FfIBP (an IBP from Flavobacterium frigoris PS1) was cloned and produced in Pichia pastoris using fed-batch fermentation with methanol feeding. 27737617 7 36 theme FfIBP 904:908 arg1 binding 893:899 the binding 889:899 the binding of FfIBP to ice molecules 889:925 These results indicate that the residues of the glycosylated site could disturb the binding of FfIBP to ice molecules. 27737617 2 37 theme intracellular 256:268 arg1 crystals 274:281 large intracellular ice crystals 250:281 large intracellular ice crystals 250:281 These IBPs prevent the formation of large intracellular ice crystals, which may be fatal to the organism. 27737617 3 38 theme fed-batch 441:449 arg1 fermentation 451:462 fed-batch fermentation 441:462 fed-batch fermentation with methanol feeding 441:484 Recently, a recombinant FfIBP (an IBP from Flavobacterium frigoris PS1) was cloned and produced in Pichia pastoris using fed-batch fermentation with methanol feeding. 27737617 2 39 theme large 250:254 arg1 crystals 274:281 large intracellular ice crystals 250:281 large intracellular ice crystals 250:281 These IBPs prevent the formation of large intracellular ice crystals, which may be fatal to the organism. 27737617 4 40 theme glycosylation 558:570 arg1 site 572:575 a glycosylation site 556:575 a glycosylation site 556:575 In this study, we demonstrate that FfIBP produced by P. pastoris has a glycosylation site, which diminishes the thermal hysteresis activity of FfIBP. 27737617 0 41 theme Pichia 77:82 arg1 pastoris 84:91 recombinant Pichia pastoris 65:91 recombinant Pichia pastoris 65:91 Improving thermal hysteresis activity of antifreeze protein from recombinant Pichia pastoris by removal of N-glycosylation. 27737617 4 42 theme thermal 599:605 arg1 activity 618:625 the thermal hysteresis activity 595:625 the thermal hysteresis activity of FfIBP 595:634 In this study, we demonstrate that FfIBP produced by P. pastoris has a glycosylation site, which diminishes the thermal hysteresis activity of FfIBP. 27737617 1 43 theme subzero 140:146 arg1 environment 148:158 a subzero environment 138:158 a subzero environment 138:158 To survive in a subzero environment, polar organisms produce ice-binding proteins (IBPs). 27737617 0 44 theme recombinant 65:75 arg1 pastoris 84:91 recombinant Pichia pastoris 65:91 recombinant Pichia pastoris 65:91 Improving thermal hysteresis activity of antifreeze protein from recombinant Pichia pastoris by removal of N-glycosylation. 27737617 0 45 from activity 29:36 arg1 pastoris 84:91 recombinant Pichia pastoris 65:91 recombinant Pichia pastoris 65:91 Improving thermal hysteresis activity of antifreeze protein from recombinant Pichia pastoris by removal of N-glycosylation. 27737617 7 46 theme glycosylated 857:868 arg1 site 870:873 the glycosylated site 853:873 the glycosylated site 853:873 These results indicate that the residues of the glycosylated site could disturb the binding of FfIBP to ice molecules. 26678161 0 0 theme Pichia 85:90 arg1 pastoris 92:99 Pichia pastoris 85:99 Pichia pastoris 85:99 High level expression and purification of active recombinant human interleukin-15 in Pichia pastoris. 26678161 0 1 from expression 11:20 arg1 pastoris 92:99 Pichia pastoris 85:99 Pichia pastoris 85:99 High level expression and purification of active recombinant human interleukin-15 in Pichia pastoris. 26678161 3 2 theme DNA 415:417 arg1 fragment 419:426 a DNA fragment 413:426 a DNA fragment containing the mature human IL-15 sequence 413:469 In this study, a DNA fragment containing the mature human IL-15 sequence was cloned into pPICZaA vector, generating a fusion protein with the alpha factor signal sequence in the N-terminus and 6×His as well as c-Myc tags in the C-terminus. 26678161 7 3 theme MALDI-TOF-TOF 1074:1086 arg1 analysis 1088:1095 MALDI-TOF-TOF analysis 1074:1095 MALDI-TOF-TOF analysis 1074:1095 Mass spectrometry and MALDI-TOF-TOF analysis showed the purified rhIL-15 had larger molecular weights than expected, due to different degrees of N-linked glycosylation. 26678161 9 4 theme active 1463:1468 arg1 IL-15 1488:1492 active recombinant human IL-15 1463:1492 active recombinant human IL-15 from P. pastoris 1463:1509 The results demonstrate that the experimental procedure we have reported here can produce a large amount of active recombinant human IL-15 from P. pastoris. 26678161 3 5 theme factor 546:551 arg1 sequence 560:567 the alpha factor signal sequence 536:567 the alpha factor signal sequence in the N-terminus and 6×His as well as c-Myc tags in the C-terminus 536:635 In this study, a DNA fragment containing the mature human IL-15 sequence was cloned into pPICZaA vector, generating a fusion protein with the alpha factor signal sequence in the N-terminus and 6×His as well as c-Myc tags in the C-terminus. 26678161 7 6 theme Mass 1052:1055 arg1 spectrometry 1057:1068 Mass spectrometry 1052:1068 Mass spectrometry 1052:1068 Mass spectrometry and MALDI-TOF-TOF analysis showed the purified rhIL-15 had larger molecular weights than expected, due to different degrees of N-linked glycosylation. 26678161 3 7 contain containing 428:437 arg1 fragment 419:426 a DNA fragment 413:426 a DNA fragment containing the mature human IL-15 sequence 413:469 In this study, a DNA fragment containing the mature human IL-15 sequence was cloned into pPICZaA vector, generating a fusion protein with the alpha factor signal sequence in the N-terminus and 6×His as well as c-Myc tags in the C-terminus. 26678161 3 7 contain containing 428:437 arg2 sequence 462:469 the mature human IL-15 sequence 439:469 the mature human IL-15 sequence 439:469 In this study, a DNA fragment containing the mature human IL-15 sequence was cloned into pPICZaA vector, generating a fusion protein with the alpha factor signal sequence in the N-terminus and 6×His as well as c-Myc tags in the C-terminus. 26678161 9 8 theme recombinant 1470:1480 arg1 IL-15 1488:1492 active recombinant human IL-15 1463:1492 active recombinant human IL-15 from P. pastoris 1463:1509 The results demonstrate that the experimental procedure we have reported here can produce a large amount of active recombinant human IL-15 from P. pastoris. 26678161 3 9 theme IL-15 456:460 arg1 sequence 462:469 the mature human IL-15 sequence 439:469 the mature human IL-15 sequence 439:469 In this study, a DNA fragment containing the mature human IL-15 sequence was cloned into pPICZaA vector, generating a fusion protein with the alpha factor signal sequence in the N-terminus and 6×His as well as c-Myc tags in the C-terminus. 26678161 7 10 theme purified 1108:1115 arg1 rhIL-15 1117:1123 the purified rhIL-15 1104:1123 the purified rhIL-15 1104:1123 Mass spectrometry and MALDI-TOF-TOF analysis showed the purified rhIL-15 had larger molecular weights than expected, due to different degrees of N-linked glycosylation. 26678161 6 11 theme affinity 951:958 arg1 chromatography 960:973 Ni(+)-NTA affinity chromatography 941:973 chromatography 960:973 The rhIL-15 was purified by Ni(+)-NTA affinity chromatography, followed by DEAE anion exchange, yielding over 95% highly purified rhIL-15. 26678161 9 12 from amount 1453:1458 arg1 pastoris 1502:1509 P. pastoris 1499:1509 P. pastoris 1499:1509 The results demonstrate that the experimental procedure we have reported here can produce a large amount of active recombinant human IL-15 from P. pastoris. 26678161 7 13 theme molecular 1136:1144 arg1 weights 1146:1152 larger molecular weights 1129:1152 larger molecular weights 1129:1152 Mass spectrometry and MALDI-TOF-TOF analysis showed the purified rhIL-15 had larger molecular weights than expected, due to different degrees of N-linked glycosylation. 26678161 5 14 dep rhIL-15 866:872 arg1 mg/L 861:864 mg/L 861:864 mg/L 861:864 Recombinant yeast transformants with high-level recombinant human IL-15 (rhIL-15) production were identified, which secrete as much as 75 mg/L rhIL-15 after 3 days of induction by methanol. 26678161 5 15 theme yeast 735:739 arg1 transformants 741:753 Recombinant yeast transformants 723:753 Recombinant yeast transformants with high-level recombinant human IL-15 (rhIL-15) production 723:814 Recombinant yeast transformants with high-level recombinant human IL-15 (rhIL-15) production were identified, which secrete as much as 75 mg/L rhIL-15 after 3 days of induction by methanol. 26678161 2 16 theme B 365:365 arg1 cells 391:395 T, B and natural killer (NK) cells 362:395 T, B and natural killer (NK) cells 362:395 IL-15 exhibits a broad biological activity and induces the differentiation and proliferation of T, B and natural killer (NK) cells. 26678161 3 17 theme mature 443:448 arg1 sequence 462:469 the mature human IL-15 sequence 439:469 the mature human IL-15 sequence 439:469 In this study, a DNA fragment containing the mature human IL-15 sequence was cloned into pPICZaA vector, generating a fusion protein with the alpha factor signal sequence in the N-terminus and 6×His as well as c-Myc tags in the C-terminus. 26678161 7 18 theme glycosylation 1206:1218 arg1 degrees 1186:1192 different degrees 1176:1192 different degrees of N-linked glycosylation 1176:1218 Mass spectrometry and MALDI-TOF-TOF analysis showed the purified rhIL-15 had larger molecular weights than expected, due to different degrees of N-linked glycosylation. 26678161 5 19 theme high-level 760:769 arg1 production 805:814 high-level recombinant human IL-15 (rhIL-15) production 760:814 high-level recombinant human IL-15 (rhIL-15) production 760:814 Recombinant yeast transformants with high-level recombinant human IL-15 (rhIL-15) production were identified, which secrete as much as 75 mg/L rhIL-15 after 3 days of induction by methanol. 26678161 3 20 from sequence 560:567 arg1 6×His 591:595 6×His 591:595 6×His 591:595 In this study, a DNA fragment containing the mature human IL-15 sequence was cloned into pPICZaA vector, generating a fusion protein with the alpha factor signal sequence in the N-terminus and 6×His as well as c-Myc tags in the C-terminus. 26678161 3 20 from sequence 560:567 arg1 N-terminus 576:585 N-terminus 576:585 N-terminus 576:585 In this study, a DNA fragment containing the mature human IL-15 sequence was cloned into pPICZaA vector, generating a fusion protein with the alpha factor signal sequence in the N-terminus and 6×His as well as c-Myc tags in the C-terminus. 26678161 3 20 from sequence 560:567 arg1 C-terminus 626:635 the C-terminus 622:635 the C-terminus 622:635 In this study, a DNA fragment containing the mature human IL-15 sequence was cloned into pPICZaA vector, generating a fusion protein with the alpha factor signal sequence in the N-terminus and 6×His as well as c-Myc tags in the C-terminus. 26678161 3 21 theme c-Myc 608:612 arg1 tags 614:617 c-Myc tags 608:617 the alpha factor signal sequence in the N-terminus and 6×His as well as c-Myc tags in the C-terminus 536:635 In this study, a DNA fragment containing the mature human IL-15 sequence was cloned into pPICZaA vector, generating a fusion protein with the alpha factor signal sequence in the N-terminus and 6×His as well as c-Myc tags in the C-terminus. 26678161 3 22 theme human 450:454 arg1 sequence 462:469 the mature human IL-15 sequence 439:469 the mature human IL-15 sequence 439:469 In this study, a DNA fragment containing the mature human IL-15 sequence was cloned into pPICZaA vector, generating a fusion protein with the alpha factor signal sequence in the N-terminus and 6×His as well as c-Myc tags in the C-terminus. 26678161 5 23 theme recombinant 771:781 arg1 production 805:814 high-level recombinant human IL-15 (rhIL-15) production 760:814 high-level recombinant human IL-15 (rhIL-15) production 760:814 Recombinant yeast transformants with high-level recombinant human IL-15 (rhIL-15) production were identified, which secrete as much as 75 mg/L rhIL-15 after 3 days of induction by methanol. 26678161 0 24 theme level 5:9 arg1 expression 11:20 High level expression 0:20 High level expression 0:20 High level expression and purification of active recombinant human interleukin-15 in Pichia pastoris. 26678161 0 25 from purification 26:37 arg1 pastoris 92:99 Pichia pastoris 85:99 Pichia pastoris 85:99 High level expression and purification of active recombinant human interleukin-15 in Pichia pastoris. 26678161 9 26 dep procedure 1401:1409 arg1 reported 1419:1426 reported 1419:1426 have reported here 1414:1431 The results demonstrate that the experimental procedure we have reported here can produce a large amount of active recombinant human IL-15 from P. pastoris. 26678161 5 27 theme human 783:787 arg1 production 805:814 high-level recombinant human IL-15 (rhIL-15) production 760:814 high-level recombinant human IL-15 (rhIL-15) production 760:814 Recombinant yeast transformants with high-level recombinant human IL-15 (rhIL-15) production were identified, which secrete as much as 75 mg/L rhIL-15 after 3 days of induction by methanol. 26678161 0 28 theme High 0:3 arg1 expression 11:20 High level expression 0:20 High level expression 0:20 High level expression and purification of active recombinant human interleukin-15 in Pichia pastoris. 26678161 7 29 link N-linked 1197:1204 arg1 glycosylation 1206:1218 N-linked glycosylation 1197:1218 N-linked glycosylation 1197:1218 Mass spectrometry and MALDI-TOF-TOF analysis showed the purified rhIL-15 had larger molecular weights than expected, due to different degrees of N-linked glycosylation. 26678161 3 30 theme pPICZaA 487:493 arg1 vector 495:500 pPICZaA vector 487:500 pPICZaA vector 487:500 In this study, a DNA fragment containing the mature human IL-15 sequence was cloned into pPICZaA vector, generating a fusion protein with the alpha factor signal sequence in the N-terminus and 6×His as well as c-Myc tags in the C-terminus. 26678161 8 31 theme biological 1225:1234 arg1 activity 1236:1243 The biological activity 1221:1243 The biological activity of the rhIL-15 proteins 1221:1267 The biological activity of the rhIL-15 proteins was measured by its ability to enhance cellular proliferation of CTLL-2 and NK cells. 26678161 5 32 theme IL-15 789:793 arg1 production 805:814 high-level recombinant human IL-15 (rhIL-15) production 760:814 high-level recombinant human IL-15 (rhIL-15) production 760:814 Recombinant yeast transformants with high-level recombinant human IL-15 (rhIL-15) production were identified, which secrete as much as 75 mg/L rhIL-15 after 3 days of induction by methanol. 26678161 2 33 theme killer 379:384 arg1 cells 391:395 T, B and natural killer (NK) cells 362:395 T, B and natural killer (NK) cells 362:395 IL-15 exhibits a broad biological activity and induces the differentiation and proliferation of T, B and natural killer (NK) cells. 26678161 4 34 theme Pichia 694:699 arg1 X-33 717:720 Pichia pastoris strain X-33 694:720 Pichia pastoris strain X-33 694:720 The resulting plasmid was integrated into the genome of Pichia pastoris strain X-33. 26678161 5 35 with transformants 741:753 arg1 production 805:814 high-level recombinant human IL-15 (rhIL-15) production 760:814 high-level recombinant human IL-15 (rhIL-15) production 760:814 Recombinant yeast transformants with high-level recombinant human IL-15 (rhIL-15) production were identified, which secrete as much as 75 mg/L rhIL-15 after 3 days of induction by methanol. 26678161 9 36 theme human 1482:1486 arg1 IL-15 1488:1492 active recombinant human IL-15 1463:1492 active recombinant human IL-15 from P. pastoris 1463:1509 The results demonstrate that the experimental procedure we have reported here can produce a large amount of active recombinant human IL-15 from P. pastoris. 26678161 4 37 theme resulting 642:650 arg1 plasmid 652:658 The resulting plasmid 638:658 The resulting plasmid 638:658 The resulting plasmid was integrated into the genome of Pichia pastoris strain X-33. 26678161 1 38 theme α-helix 176:182 arg1 family 191:196 the four α-helix bundle family 167:196 the four α-helix bundle family of cytokines which include IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21 167:263 Interleukin-15 (IL-15) is a pleiotropic cytokine and a member of the four α-helix bundle family of cytokines which include IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21. 26678161 2 39 theme natural 371:377 arg1 NK 387:388 NK 387:388 NK 387:388 IL-15 exhibits a broad biological activity and induces the differentiation and proliferation of T, B and natural killer (NK) cells. 26678161 2 39 theme natural 371:377 arg1 killer 379:384 natural killer 371:384 natural killer (NK) 371:389 IL-15 exhibits a broad biological activity and induces the differentiation and proliferation of T, B and natural killer (NK) cells. 26678161 6 40 theme purified 1034:1041 arg1 rhIL-15 1043:1049 95% highly purified rhIL-15 1023:1049 95% highly purified rhIL-15 1023:1049 The rhIL-15 was purified by Ni(+)-NTA affinity chromatography, followed by DEAE anion exchange, yielding over 95% highly purified rhIL-15. 26678161 6 41 theme % 1025:1025 arg1 rhIL-15 1043:1049 95% highly purified rhIL-15 1023:1049 95% highly purified rhIL-15 1023:1049 The rhIL-15 was purified by Ni(+)-NTA affinity chromatography, followed by DEAE anion exchange, yielding over 95% highly purified rhIL-15. 26678161 3 42 theme signal 553:558 arg1 sequence 560:567 the alpha factor signal sequence 536:567 the alpha factor signal sequence in the N-terminus and 6×His as well as c-Myc tags in the C-terminus 536:635 In this study, a DNA fragment containing the mature human IL-15 sequence was cloned into pPICZaA vector, generating a fusion protein with the alpha factor signal sequence in the N-terminus and 6×His as well as c-Myc tags in the C-terminus. 26678161 6 43 theme -NTA 946:949 arg1 chromatography 960:973 Ni(+)-NTA affinity chromatography 941:973 chromatography 960:973 The rhIL-15 was purified by Ni(+)-NTA affinity chromatography, followed by DEAE anion exchange, yielding over 95% highly purified rhIL-15. 26678161 1 44 theme bundle 184:189 arg1 family 191:196 the four α-helix bundle family 167:196 the four α-helix bundle family of cytokines which include IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21 167:263 Interleukin-15 (IL-15) is a pleiotropic cytokine and a member of the four α-helix bundle family of cytokines which include IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21. 26678161 6 45 theme DEAE 988:991 arg1 exchange 999:1006 DEAE anion exchange 988:1006 DEAE anion exchange 988:1006 The rhIL-15 was purified by Ni(+)-NTA affinity chromatography, followed by DEAE anion exchange, yielding over 95% highly purified rhIL-15. 26678161 8 46 theme cellular 1308:1315 arg1 proliferation 1317:1329 cellular proliferation 1308:1329 cellular proliferation of CTLL-2 and NK cells 1308:1352 The biological activity of the rhIL-15 proteins was measured by its ability to enhance cellular proliferation of CTLL-2 and NK cells. 26678161 4 47 theme strain 710:715 arg1 X-33 717:720 Pichia pastoris strain X-33 694:720 Pichia pastoris strain X-33 694:720 The resulting plasmid was integrated into the genome of Pichia pastoris strain X-33. 26678161 1 48 theme family 191:196 arg1 cytokine 142:149 a pleiotropic cytokine 128:149 a pleiotropic cytokine 128:149 Interleukin-15 (IL-15) is a pleiotropic cytokine and a member of the four α-helix bundle family of cytokines which include IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21. 26678161 1 48 theme family 191:196 arg1 member 157:162 a member 155:162 a member of the four α-helix bundle family of cytokines which include IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21 155:263 Interleukin-15 (IL-15) is a pleiotropic cytokine and a member of the four α-helix bundle family of cytokines which include IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21. 26678161 1 48 theme family 191:196 arg1 Interleukin-15 102:115 Interleukin-15 102:115 Interleukin-15 (IL-15) 102:123 Interleukin-15 (IL-15) is a pleiotropic cytokine and a member of the four α-helix bundle family of cytokines which include IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21. 26678161 7 49 dep showed 1097:1102 arg1 had 1125:1127 had 1125:1127 had 1125:1127 Mass spectrometry and MALDI-TOF-TOF analysis showed the purified rhIL-15 had larger molecular weights than expected, due to different degrees of N-linked glycosylation. 26678161 3 50 theme alpha 540:544 arg1 sequence 560:567 the alpha factor signal sequence 536:567 the alpha factor signal sequence in the N-terminus and 6×His as well as c-Myc tags in the C-terminus 536:635 In this study, a DNA fragment containing the mature human IL-15 sequence was cloned into pPICZaA vector, generating a fusion protein with the alpha factor signal sequence in the N-terminus and 6×His as well as c-Myc tags in the C-terminus. 26678161 4 51 theme pastoris 701:708 arg1 X-33 717:720 Pichia pastoris strain X-33 694:720 Pichia pastoris strain X-33 694:720 The resulting plasmid was integrated into the genome of Pichia pastoris strain X-33. 26678161 2 52 theme T 362:362 arg1 cells 391:395 T, B and natural killer (NK) cells 362:395 T, B and natural killer (NK) cells 362:395 IL-15 exhibits a broad biological activity and induces the differentiation and proliferation of T, B and natural killer (NK) cells. 26678161 2 53 theme cells 391:395 arg1 proliferation 345:357 proliferation 345:357 proliferation 345:357 IL-15 exhibits a broad biological activity and induces the differentiation and proliferation of T, B and natural killer (NK) cells. 26678161 2 53 theme cells 391:395 arg1 differentiation 325:339 differentiation 325:339 differentiation 325:339 IL-15 exhibits a broad biological activity and induces the differentiation and proliferation of T, B and natural killer (NK) cells. 26678161 8 54 theme CTLL-2 1334:1339 arg1 proliferation 1317:1329 cellular proliferation 1308:1329 cellular proliferation of CTLL-2 and NK cells 1308:1352 The biological activity of the rhIL-15 proteins was measured by its ability to enhance cellular proliferation of CTLL-2 and NK cells. 26678161 9 55 theme experimental 1388:1399 arg1 procedure 1401:1409 the experimental procedure 1384:1409 the experimental procedure we have reported here 1384:1431 The results demonstrate that the experimental procedure we have reported here can produce a large amount of active recombinant human IL-15 from P. pastoris. 26678161 0 56 theme human 61:65 arg1 interleukin-15 67:80 active recombinant human interleukin-15 42:80 active recombinant human interleukin-15 42:80 High level expression and purification of active recombinant human interleukin-15 in Pichia pastoris. 26678161 7 57 theme different 1176:1184 arg1 degrees 1186:1192 different degrees 1176:1192 different degrees of N-linked glycosylation 1176:1218 Mass spectrometry and MALDI-TOF-TOF analysis showed the purified rhIL-15 had larger molecular weights than expected, due to different degrees of N-linked glycosylation. 26678161 2 58 theme biological 289:298 arg1 activity 300:307 a broad biological activity 281:307 a broad biological activity 281:307 IL-15 exhibits a broad biological activity and induces the differentiation and proliferation of T, B and natural killer (NK) cells. 26678161 0 59 theme active 42:47 arg1 interleukin-15 67:80 active recombinant human interleukin-15 42:80 active recombinant human interleukin-15 42:80 High level expression and purification of active recombinant human interleukin-15 in Pichia pastoris. 26678161 8 60 theme NK 1345:1346 arg1 cells 1348:1352 NK cells 1345:1352 NK cells 1345:1352 The biological activity of the rhIL-15 proteins was measured by its ability to enhance cellular proliferation of CTLL-2 and NK cells. 26678161 4 61 theme X-33 717:720 arg1 genome 684:689 the genome 680:689 the genome of Pichia pastoris strain X-33 680:720 The resulting plasmid was integrated into the genome of Pichia pastoris strain X-33. 26678161 2 62 theme broad 283:287 arg1 activity 300:307 a broad biological activity 281:307 a broad biological activity 281:307 IL-15 exhibits a broad biological activity and induces the differentiation and proliferation of T, B and natural killer (NK) cells. 26678161 3 63 from tags 614:617 arg1 6×His 591:595 6×His 591:595 6×His 591:595 In this study, a DNA fragment containing the mature human IL-15 sequence was cloned into pPICZaA vector, generating a fusion protein with the alpha factor signal sequence in the N-terminus and 6×His as well as c-Myc tags in the C-terminus. 26678161 3 63 from tags 614:617 arg1 N-terminus 576:585 N-terminus 576:585 N-terminus 576:585 In this study, a DNA fragment containing the mature human IL-15 sequence was cloned into pPICZaA vector, generating a fusion protein with the alpha factor signal sequence in the N-terminus and 6×His as well as c-Myc tags in the C-terminus. 26678161 3 63 from tags 614:617 arg1 C-terminus 626:635 the C-terminus 622:635 the C-terminus 622:635 In this study, a DNA fragment containing the mature human IL-15 sequence was cloned into pPICZaA vector, generating a fusion protein with the alpha factor signal sequence in the N-terminus and 6×His as well as c-Myc tags in the C-terminus. 26678161 9 64 theme IL-15 1488:1492 arg1 IL-15 1488:1492 active recombinant human IL-15 1463:1492 active recombinant human IL-15 from P. pastoris 1463:1509 The results demonstrate that the experimental procedure we have reported here can produce a large amount of active recombinant human IL-15 from P. pastoris. 26678161 9 64 theme IL-15 1488:1492 arg1 amount 1453:1458 a large amount 1445:1458 a large amount of active recombinant human IL-15 from P. pastoris 1445:1509 The results demonstrate that the experimental procedure we have reported here can produce a large amount of active recombinant human IL-15 from P. pastoris. 26678161 8 65 theme proteins 1260:1267 arg1 activity 1236:1243 The biological activity 1221:1243 The biological activity of the rhIL-15 proteins 1221:1267 The biological activity of the rhIL-15 proteins was measured by its ability to enhance cellular proliferation of CTLL-2 and NK cells. 26678161 7 66 theme larger 1129:1134 arg1 weights 1146:1152 larger molecular weights 1129:1152 larger molecular weights 1129:1152 Mass spectrometry and MALDI-TOF-TOF analysis showed the purified rhIL-15 had larger molecular weights than expected, due to different degrees of N-linked glycosylation. 26678161 9 67 theme large 1447:1451 arg1 IL-15 1488:1492 active recombinant human IL-15 1463:1492 active recombinant human IL-15 from P. pastoris 1463:1509 The results demonstrate that the experimental procedure we have reported here can produce a large amount of active recombinant human IL-15 from P. pastoris. 26678161 9 67 theme large 1447:1451 arg1 amount 1453:1458 a large amount 1445:1458 a large amount of active recombinant human IL-15 from P. pastoris 1445:1509 The results demonstrate that the experimental procedure we have reported here can produce a large amount of active recombinant human IL-15 from P. pastoris. 26678161 1 68 theme cytokines 201:209 arg1 family 191:196 the four α-helix bundle family 167:196 the four α-helix bundle family of cytokines which include IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21 167:263 Interleukin-15 (IL-15) is a pleiotropic cytokine and a member of the four α-helix bundle family of cytokines which include IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21. 26678161 6 69 theme 95 1023:1024 arg1 % 1025:1025 % 1025:1025 % 1025:1025 The rhIL-15 was purified by Ni(+)-NTA affinity chromatography, followed by DEAE anion exchange, yielding over 95% highly purified rhIL-15. 26678161 2 70 dep differentiation 325:339 arg1 the 321:323 the 321:323 the 321:323 IL-15 exhibits a broad biological activity and induces the differentiation and proliferation of T, B and natural killer (NK) cells. 26678161 5 71 dep mg/L 861:864 arg1 75 858:859 75 858:859 75 858:859 Recombinant yeast transformants with high-level recombinant human IL-15 (rhIL-15) production were identified, which secrete as much as 75 mg/L rhIL-15 after 3 days of induction by methanol. 26678161 6 72 theme anion 993:997 arg1 exchange 999:1006 DEAE anion exchange 988:1006 DEAE anion exchange 988:1006 The rhIL-15 was purified by Ni(+)-NTA affinity chromatography, followed by DEAE anion exchange, yielding over 95% highly purified rhIL-15. 26678161 9 73 from pastoris 1502:1509 arg1 IL-15 1488:1492 active recombinant human IL-15 1463:1492 active recombinant human IL-15 from P. pastoris 1463:1509 The results demonstrate that the experimental procedure we have reported here can produce a large amount of active recombinant human IL-15 from P. pastoris. 26678161 9 73 from pastoris 1502:1509 arg1 amount 1453:1458 a large amount 1445:1458 a large amount of active recombinant human IL-15 from P. pastoris 1445:1509 The results demonstrate that the experimental procedure we have reported here can produce a large amount of active recombinant human IL-15 from P. pastoris. 26678161 0 74 theme interleukin-15 67:80 arg1 expression 11:20 High level expression 0:20 High level expression 0:20 High level expression and purification of active recombinant human interleukin-15 in Pichia pastoris. 26678161 0 74 theme interleukin-15 67:80 arg1 purification 26:37 purification 26:37 purification 26:37 High level expression and purification of active recombinant human interleukin-15 in Pichia pastoris. 26678161 8 75 theme cells 1348:1352 arg1 proliferation 1317:1329 cellular proliferation 1308:1329 cellular proliferation of CTLL-2 and NK cells 1308:1352 The biological activity of the rhIL-15 proteins was measured by its ability to enhance cellular proliferation of CTLL-2 and NK cells. 26678161 3 76 theme fusion 516:521 arg1 protein 523:529 a fusion protein 514:529 a fusion protein 514:529 In this study, a DNA fragment containing the mature human IL-15 sequence was cloned into pPICZaA vector, generating a fusion protein with the alpha factor signal sequence in the N-terminus and 6×His as well as c-Myc tags in the C-terminus. 26678161 5 77 theme Recombinant 723:733 arg1 transformants 741:753 Recombinant yeast transformants 723:753 Recombinant yeast transformants with high-level recombinant human IL-15 (rhIL-15) production 723:814 Recombinant yeast transformants with high-level recombinant human IL-15 (rhIL-15) production were identified, which secrete as much as 75 mg/L rhIL-15 after 3 days of induction by methanol. 26678161 1 78 theme pleiotropic 130:140 arg1 cytokine 142:149 a pleiotropic cytokine 128:149 a pleiotropic cytokine 128:149 Interleukin-15 (IL-15) is a pleiotropic cytokine and a member of the four α-helix bundle family of cytokines which include IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21. 26678161 1 78 theme pleiotropic 130:140 arg1 Interleukin-15 102:115 Interleukin-15 102:115 Interleukin-15 (IL-15) 102:123 Interleukin-15 (IL-15) is a pleiotropic cytokine and a member of the four α-helix bundle family of cytokines which include IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21. 26678161 7 79 theme N-linked 1197:1204 arg1 glycosylation 1206:1218 N-linked glycosylation 1197:1218 N-linked glycosylation 1197:1218 Mass spectrometry and MALDI-TOF-TOF analysis showed the purified rhIL-15 had larger molecular weights than expected, due to different degrees of N-linked glycosylation. 26678161 0 80 theme recombinant 49:59 arg1 interleukin-15 67:80 active recombinant human interleukin-15 42:80 active recombinant human interleukin-15 42:80 High level expression and purification of active recombinant human interleukin-15 in Pichia pastoris. 26678161 5 81 theme induction 890:898 arg1 days 882:885 3 days 880:885 3 days of induction by methanol 880:910 Recombinant yeast transformants with high-level recombinant human IL-15 (rhIL-15) production were identified, which secrete as much as 75 mg/L rhIL-15 after 3 days of induction by methanol. 26678161 5 82 theme rhIL-15 796:802 arg1 production 805:814 high-level recombinant human IL-15 (rhIL-15) production 760:814 high-level recombinant human IL-15 (rhIL-15) production 760:814 Recombinant yeast transformants with high-level recombinant human IL-15 (rhIL-15) production were identified, which secrete as much as 75 mg/L rhIL-15 after 3 days of induction by methanol. 28739903 4 0 theme same 907:910 arg1 glycoprotein 912:923 the same glycoprotein 903:923 the same glycoprotein 903:923 Questions remain on how this single enzyme can flag misfolded glycoproteins of different sizes and shapes for ER retention and how it can span variable distances between the site of misfold and a glucose-accepting N-linked glycan on the same glycoprotein. 28739903 2 1 theme single 348:353 arg1 enzyme 329:334 The enzyme 325:334 The enzyme 325:334 The enzyme acts as the single glycoprotein folding quality control checkpoint: it selectively reglucosylates misfolded glycoproteins, promotes their association with ER lectins and associated chaperones, and prevents premature secretion from the ER. 28739903 2 1 theme single 348:353 arg1 checkpoint 392:401 the single glycoprotein folding quality control checkpoint 344:401 the single glycoprotein folding quality control checkpoint 344:401 The enzyme acts as the single glycoprotein folding quality control checkpoint: it selectively reglucosylates misfolded glycoproteins, promotes their association with ER lectins and associated chaperones, and prevents premature secretion from the ER. 28739903 9 2 theme different 1709:1717 arg1 substrates 1719:1728 its many different substrates 1700:1728 its many different substrates 1700:1728 The intrinsic flexibility of the TRXL domains of UGGT may therefore endow the enzyme with the promiscuity needed to recognize and reglucosylate its many different substrates and/or enable reglucosylation of N-linked glycans situated at variable distances from the site of misfold. 28739903 6 3 theme fourth 1221:1226 arg1 domain 1233:1238 the fourth TRXL domain 1217:1238 the fourth TRXL domain 1217:1238 The fold of the molecule is topologically complex, with the first β-sandwich and the fourth TRXL domain being encoded by nonconsecutive stretches of sequence. 28739903 4 4 theme N-linked 884:891 arg1 glycan 893:898 a glucose-accepting N-linked glycan 864:898 a glucose-accepting N-linked glycan 864:898 Questions remain on how this single enzyme can flag misfolded glycoproteins of different sizes and shapes for ER retention and how it can span variable distances between the site of misfold and a glucose-accepting N-linked glycan on the same glycoprotein. 28739903 1 5 theme endoplasmic 197:207 arg1 reticulum 209:217 the endoplasmic reticulum 193:217 the endoplasmic reticulum (ER) 193:222 Glycoproteins traversing the eukaryotic secretory pathway begin life in the endoplasmic reticulum (ER), where their folding is surveyed by the 170-kDa UDP-glucose:glycoprotein glucosyltransferase (UGGT). 28739903 1 5 theme endoplasmic 197:207 arg1 ER 220:221 ER 220:221 ER 220:221 Glycoproteins traversing the eukaryotic secretory pathway begin life in the endoplasmic reticulum (ER), where their folding is surveyed by the 170-kDa UDP-glucose:glycoprotein glucosyltransferase (UGGT). 28739903 9 6 theme N-linked 1763:1770 arg1 glycans 1772:1778 N-linked glycans 1763:1778 N-linked glycans situated at variable distances from the site of misfold 1763:1834 The intrinsic flexibility of the TRXL domains of UGGT may therefore endow the enzyme with the promiscuity needed to recognize and reglucosylate its many different substrates and/or enable reglucosylation of N-linked glycans situated at variable distances from the site of misfold. 28739903 6 7 theme first 1196:1200 arg1 β-sandwich 1202:1211 the first β-sandwich 1192:1211 the first β-sandwich 1192:1211 The fold of the molecule is topologically complex, with the first β-sandwich and the fourth TRXL domain being encoded by nonconsecutive stretches of sequence. 28739903 6 8 theme sequence 1285:1292 arg1 stretches 1272:1280 nonconsecutive stretches 1257:1280 nonconsecutive stretches of sequence 1257:1292 The fold of the molecule is topologically complex, with the first β-sandwich and the fourth TRXL domain being encoded by nonconsecutive stretches of sequence. 28739903 3 9 theme structural 598:607 arg1 determination 609:621 structural determination 598:621 structural determination 598:621 UGGT has long resisted structural determination and sequence-based domain boundary prediction. 28739903 9 10 theme situated 1780:1787 arg1 glycans 1772:1778 N-linked glycans 1763:1778 N-linked glycans situated at variable distances from the site of misfold 1763:1834 The intrinsic flexibility of the TRXL domains of UGGT may therefore endow the enzyme with the promiscuity needed to recognize and reglucosylate its many different substrates and/or enable reglucosylation of N-linked glycans situated at variable distances from the site of misfold. 28739903 9 11 with enzyme 1634:1639 arg1 promiscuity 1650:1660 the promiscuity 1646:1660 the promiscuity needed to recognize and reglucosylate its many different substrates 1646:1728 The intrinsic flexibility of the TRXL domains of UGGT may therefore endow the enzyme with the promiscuity needed to recognize and reglucosylate its many different substrates and/or enable reglucosylation of N-linked glycans situated at variable distances from the site of misfold. 28739903 9 12 theme variable 1792:1799 arg1 distances 1801:1809 variable distances 1792:1809 variable distances from the site of misfold 1792:1834 The intrinsic flexibility of the TRXL domains of UGGT may therefore endow the enzyme with the promiscuity needed to recognize and reglucosylate its many different substrates and/or enable reglucosylation of N-linked glycans situated at variable distances from the site of misfold. 28739903 3 13 theme domain 642:647 arg1 prediction 658:667 sequence-based domain boundary prediction 627:667 sequence-based domain boundary prediction 627:667 UGGT has long resisted structural determination and sequence-based domain boundary prediction. 28739903 1 14 gly glycoprotein 284:295 arg1 glycoprotein 284:295 glycoprotein glucosyltransferase 284:315 Glycoproteins traversing the eukaryotic secretory pathway begin life in the endoplasmic reticulum (ER), where their folding is surveyed by the 170-kDa UDP-glucose:glycoprotein glucosyltransferase (UGGT). 121:323 Glycoproteins traversing the eukaryotic secretory pathway begin life in the endoplasmic reticulum (ER), where their folding is surveyed by the 170-kDa UDP-glucose:glycoprotein glucosyltransferase (UGGT). 28739903 6 15 theme nonconsecutive 1257:1270 arg1 stretches 1272:1280 nonconsecutive stretches 1257:1280 nonconsecutive stretches of sequence 1257:1292 The fold of the molecule is topologically complex, with the first β-sandwich and the fourth TRXL domain being encoded by nonconsecutive stretches of sequence. 28739903 4 16 gly glycoproteins 732:744 arg1 glycoproteins 732:744 misfolded glycoproteins 722:744 misfolded glycoproteins of different sizes and shapes for ER retention 722:791 Questions remain on how this single enzyme can flag misfolded glycoproteins of different sizes and shapes for ER retention and how it can span variable distances between the site of misfold and a glucose-accepting N-linked glycan on the same glycoprotein. 28739903 2 17 with association 474:484 arg1 lectins 494:500 ER lectins 491:500 ER lectins 491:500 The enzyme acts as the single glycoprotein folding quality control checkpoint: it selectively reglucosylates misfolded glycoproteins, promotes their association with ER lectins and associated chaperones, and prevents premature secretion from the ER. 28739903 2 17 with association 474:484 arg1 chaperones 517:526 associated chaperones 506:526 associated chaperones 506:526 The enzyme acts as the single glycoprotein folding quality control checkpoint: it selectively reglucosylates misfolded glycoproteins, promotes their association with ER lectins and associated chaperones, and prevents premature secretion from the ER. 28739903 9 18 theme intrinsic 1560:1568 arg1 flexibility 1570:1580 The intrinsic flexibility 1556:1580 The intrinsic flexibility of the TRXL domains of UGGT 1556:1608 The intrinsic flexibility of the TRXL domains of UGGT may therefore endow the enzyme with the promiscuity needed to recognize and reglucosylate its many different substrates and/or enable reglucosylation of N-linked glycans situated at variable distances from the site of misfold. 28739903 7 19 theme TRXL 1403:1406 arg1 domains 1408:1414 the TRXL domains 1399:1414 the TRXL domains 1399:1414 In addition to the crystal structures, a 15-Å cryo-EM reconstruction reveals interdomain flexibility of the TRXL domains. 28739903 8 20 theme point 1433:1437 arg1 mutants 1439:1445 Double cysteine point mutants 1417:1445 Double cysteine point mutants that engineer extra interdomain disulfide bridges 1417:1495 Double cysteine point mutants that engineer extra interdomain disulfide bridges rigidify the UGGT structure and exhibit impaired activity. 28739903 4 21 from site 844:847 arg1 glycoprotein 912:923 the same glycoprotein 903:923 the same glycoprotein 903:923 Questions remain on how this single enzyme can flag misfolded glycoproteins of different sizes and shapes for ER retention and how it can span variable distances between the site of misfold and a glucose-accepting N-linked glycan on the same glycoprotein. 28739903 5 22 theme eukaryotic 968:977 arg1 UGGT 979:982 a full-length eukaryotic UGGT 954:982 a full-length eukaryotic UGGT 954:982 Here, crystal structures of a full-length eukaryotic UGGT reveal four thioredoxin-like (TRXL) domains arranged in a long arc that terminates in two β-sandwiches tightly clasping the glucosyltransferase domain. 28739903 5 23 theme full-length 956:966 arg1 UGGT 979:982 a full-length eukaryotic UGGT 954:982 a full-length eukaryotic UGGT 954:982 Here, crystal structures of a full-length eukaryotic UGGT reveal four thioredoxin-like (TRXL) domains arranged in a long arc that terminates in two β-sandwiches tightly clasping the glucosyltransferase domain. 28739903 9 24 theme misfold 1828:1834 arg1 misfold 1828:1834 misfold 1828:1834 misfold 1828:1834 The intrinsic flexibility of the TRXL domains of UGGT may therefore endow the enzyme with the promiscuity needed to recognize and reglucosylate its many different substrates and/or enable reglucosylation of N-linked glycans situated at variable distances from the site of misfold. 28739903 9 24 theme misfold 1828:1834 arg1 site 1820:1823 the site 1816:1823 the site of misfold 1816:1834 The intrinsic flexibility of the TRXL domains of UGGT may therefore endow the enzyme with the promiscuity needed to recognize and reglucosylate its many different substrates and/or enable reglucosylation of N-linked glycans situated at variable distances from the site of misfold. 28739903 9 25 theme TRXL 1589:1592 arg1 UGGT 1605:1608 UGGT 1605:1608 UGGT 1605:1608 The intrinsic flexibility of the TRXL domains of UGGT may therefore endow the enzyme with the promiscuity needed to recognize and reglucosylate its many different substrates and/or enable reglucosylation of N-linked glycans situated at variable distances from the site of misfold. 28739903 9 25 theme TRXL 1589:1592 arg1 domains 1594:1600 the TRXL domains 1585:1600 the TRXL domains of UGGT 1585:1608 The intrinsic flexibility of the TRXL domains of UGGT may therefore endow the enzyme with the promiscuity needed to recognize and reglucosylate its many different substrates and/or enable reglucosylation of N-linked glycans situated at variable distances from the site of misfold. 28739903 4 26 theme different 749:757 arg1 sizes 759:763 different sizes 749:763 different sizes 749:763 Questions remain on how this single enzyme can flag misfolded glycoproteins of different sizes and shapes for ER retention and how it can span variable distances between the site of misfold and a glucose-accepting N-linked glycan on the same glycoprotein. 28739903 0 27 theme eukaryotic 75:84 arg1 checkpoint 109:118 the eukaryotic glycoprotein secretion checkpoint 71:118 the eukaryotic glycoprotein secretion checkpoint 71:118 Interdomain conformational flexibility underpins the activity of UGGT, the eukaryotic glycoprotein secretion checkpoint. 28739903 0 27 theme eukaryotic 75:84 arg1 activity 53:60 the activity 49:60 the activity of UGGT 49:68 Interdomain conformational flexibility underpins the activity of UGGT, the eukaryotic glycoprotein secretion checkpoint. 28739903 9 28 from distances 1801:1809 arg1 situated 1780:1787 situated 1780:1787 situated 1780:1787 The intrinsic flexibility of the TRXL domains of UGGT may therefore endow the enzyme with the promiscuity needed to recognize and reglucosylate its many different substrates and/or enable reglucosylation of N-linked glycans situated at variable distances from the site of misfold. 28739903 0 29 theme secretion 99:107 arg1 checkpoint 109:118 the eukaryotic glycoprotein secretion checkpoint 71:118 the eukaryotic glycoprotein secretion checkpoint 71:118 Interdomain conformational flexibility underpins the activity of UGGT, the eukaryotic glycoprotein secretion checkpoint. 28739903 0 29 theme secretion 99:107 arg1 activity 53:60 the activity 49:60 the activity of UGGT 49:68 Interdomain conformational flexibility underpins the activity of UGGT, the eukaryotic glycoprotein secretion checkpoint. 28739903 1 30 theme secretory 161:169 arg1 pathway 171:177 the eukaryotic secretory pathway 146:177 the eukaryotic secretory pathway begin life in the endoplasmic reticulum (ER), where their folding is surveyed by the 170-kDa UDP-glucose 146:282 Glycoproteins traversing the eukaryotic secretory pathway begin life in the endoplasmic reticulum (ER), where their folding is surveyed by the 170-kDa UDP-glucose:glycoprotein glucosyltransferase (UGGT). 28739903 2 31 theme premature 542:550 arg1 secretion 552:560 premature secretion 542:560 premature secretion from the ER 542:572 The enzyme acts as the single glycoprotein folding quality control checkpoint: it selectively reglucosylates misfolded glycoproteins, promotes their association with ER lectins and associated chaperones, and prevents premature secretion from the ER. 28739903 4 32 theme variable 813:820 arg1 distances 822:830 variable distances 813:830 variable distances between the site of misfold and a glucose-accepting N-linked glycan on the same glycoprotein 813:923 Questions remain on how this single enzyme can flag misfolded glycoproteins of different sizes and shapes for ER retention and how it can span variable distances between the site of misfold and a glucose-accepting N-linked glycan on the same glycoprotein. 28739903 0 33 gly glycoprotein 86:97 arg1 glycoprotein 86:97 the eukaryotic glycoprotein secretion checkpoint 71:118 the eukaryotic glycoprotein secretion checkpoint 71:118 Interdomain conformational flexibility underpins the activity of UGGT, the eukaryotic glycoprotein secretion checkpoint. 28739903 8 34 theme Double 1417:1422 arg1 mutants 1439:1445 Double cysteine point mutants 1417:1445 Double cysteine point mutants that engineer extra interdomain disulfide bridges 1417:1495 Double cysteine point mutants that engineer extra interdomain disulfide bridges rigidify the UGGT structure and exhibit impaired activity. 28739903 0 35 theme Interdomain 0:10 arg1 flexibility 27:37 Interdomain conformational flexibility 0:37 Interdomain conformational flexibility 0:37 Interdomain conformational flexibility underpins the activity of UGGT, the eukaryotic glycoprotein secretion checkpoint. 28739903 1 36 dep pathway 171:177 arg1 begin 179:183 begin 179:183 begin life in the endoplasmic reticulum (ER), where their folding is surveyed by the 170-kDa UDP-glucose 179:282 Glycoproteins traversing the eukaryotic secretory pathway begin life in the endoplasmic reticulum (ER), where their folding is surveyed by the 170-kDa UDP-glucose:glycoprotein glucosyltransferase (UGGT). 28739903 5 37 theme thioredoxin-like 996:1011 arg1 TRXL 1014:1017 TRXL 1014:1017 TRXL 1014:1017 Here, crystal structures of a full-length eukaryotic UGGT reveal four thioredoxin-like (TRXL) domains arranged in a long arc that terminates in two β-sandwiches tightly clasping the glucosyltransferase domain. 28739903 5 37 theme thioredoxin-like 996:1011 arg1 domains 1020:1026 four thioredoxin-like (TRXL) domains 991:1026 four thioredoxin-like (TRXL) domains arranged in a long arc that terminates in two β-sandwiches tightly clasping the glucosyltransferase domain 991:1133 Here, crystal structures of a full-length eukaryotic UGGT reveal four thioredoxin-like (TRXL) domains arranged in a long arc that terminates in two β-sandwiches tightly clasping the glucosyltransferase domain. 28739903 7 38 theme cryo-EM 1341:1347 arg1 reconstruction 1349:1362 a 15-Å cryo-EM reconstruction 1334:1362 a 15-Å cryo-EM reconstruction 1334:1362 In addition to the crystal structures, a 15-Å cryo-EM reconstruction reveals interdomain flexibility of the TRXL domains. 28739903 4 39 theme misfold 852:858 arg1 glycan 893:898 a glucose-accepting N-linked glycan 864:898 a glucose-accepting N-linked glycan 864:898 Questions remain on how this single enzyme can flag misfolded glycoproteins of different sizes and shapes for ER retention and how it can span variable distances between the site of misfold and a glucose-accepting N-linked glycan on the same glycoprotein. 28739903 4 39 theme misfold 852:858 arg1 misfold 852:858 misfold 852:858 misfold 852:858 Questions remain on how this single enzyme can flag misfolded glycoproteins of different sizes and shapes for ER retention and how it can span variable distances between the site of misfold and a glucose-accepting N-linked glycan on the same glycoprotein. 28739903 4 39 theme misfold 852:858 arg1 site 844:847 the site 840:847 the site of misfold and a glucose-accepting N-linked glycan on the same glycoprotein 840:923 Questions remain on how this single enzyme can flag misfolded glycoproteins of different sizes and shapes for ER retention and how it can span variable distances between the site of misfold and a glucose-accepting N-linked glycan on the same glycoprotein. 28739903 2 40 theme ER 491:492 arg1 lectins 494:500 ER lectins 491:500 ER lectins 491:500 The enzyme acts as the single glycoprotein folding quality control checkpoint: it selectively reglucosylates misfolded glycoproteins, promotes their association with ER lectins and associated chaperones, and prevents premature secretion from the ER. 28739903 8 41 theme extra 1461:1465 arg1 bridges 1489:1495 extra interdomain disulfide bridges 1461:1495 extra interdomain disulfide bridges 1461:1495 Double cysteine point mutants that engineer extra interdomain disulfide bridges rigidify the UGGT structure and exhibit impaired activity. 28739903 8 42 theme disulfide 1479:1487 arg1 bridges 1489:1495 extra interdomain disulfide bridges 1461:1495 extra interdomain disulfide bridges 1461:1495 Double cysteine point mutants that engineer extra interdomain disulfide bridges rigidify the UGGT structure and exhibit impaired activity. 28739903 5 43 theme glucosyltransferase 1108:1126 arg1 domain 1128:1133 the glucosyltransferase domain 1104:1133 the glucosyltransferase domain 1104:1133 Here, crystal structures of a full-length eukaryotic UGGT reveal four thioredoxin-like (TRXL) domains arranged in a long arc that terminates in two β-sandwiches tightly clasping the glucosyltransferase domain. 28739903 4 44 theme misfolded 722:730 arg1 glycoproteins 732:744 misfolded glycoproteins 722:744 misfolded glycoproteins of different sizes and shapes for ER retention 722:791 Questions remain on how this single enzyme can flag misfolded glycoproteins of different sizes and shapes for ER retention and how it can span variable distances between the site of misfold and a glucose-accepting N-linked glycan on the same glycoprotein. 28739903 2 45 theme quality 376:382 arg1 enzyme 329:334 The enzyme 325:334 The enzyme 325:334 The enzyme acts as the single glycoprotein folding quality control checkpoint: it selectively reglucosylates misfolded glycoproteins, promotes their association with ER lectins and associated chaperones, and prevents premature secretion from the ER. 28739903 2 45 theme quality 376:382 arg1 checkpoint 392:401 the single glycoprotein folding quality control checkpoint 344:401 the single glycoprotein folding quality control checkpoint 344:401 The enzyme acts as the single glycoprotein folding quality control checkpoint: it selectively reglucosylates misfolded glycoproteins, promotes their association with ER lectins and associated chaperones, and prevents premature secretion from the ER. 28739903 5 46 theme long 1042:1045 arg1 arc 1047:1049 a long arc 1040:1049 a long arc that terminates in two β-sandwiches tightly clasping the glucosyltransferase domain 1040:1133 Here, crystal structures of a full-length eukaryotic UGGT reveal four thioredoxin-like (TRXL) domains arranged in a long arc that terminates in two β-sandwiches tightly clasping the glucosyltransferase domain. 28739903 2 47 theme glycoprotein 355:366 arg1 enzyme 329:334 The enzyme 325:334 The enzyme 325:334 The enzyme acts as the single glycoprotein folding quality control checkpoint: it selectively reglucosylates misfolded glycoproteins, promotes their association with ER lectins and associated chaperones, and prevents premature secretion from the ER. 28739903 2 47 theme glycoprotein 355:366 arg1 checkpoint 392:401 the single glycoprotein folding quality control checkpoint 344:401 the single glycoprotein folding quality control checkpoint 344:401 The enzyme acts as the single glycoprotein folding quality control checkpoint: it selectively reglucosylates misfolded glycoproteins, promotes their association with ER lectins and associated chaperones, and prevents premature secretion from the ER. 28739903 1 48 theme 170-kDa 264:270 arg1 UDP-glucose 272:282 the 170-kDa UDP-glucose 260:282 the 170-kDa UDP-glucose 260:282 Glycoproteins traversing the eukaryotic secretory pathway begin life in the endoplasmic reticulum (ER), where their folding is surveyed by the 170-kDa UDP-glucose:glycoprotein glucosyltransferase (UGGT). 28739903 9 49 theme domains 1594:1600 arg1 flexibility 1570:1580 The intrinsic flexibility 1556:1580 The intrinsic flexibility of the TRXL domains of UGGT 1556:1608 The intrinsic flexibility of the TRXL domains of UGGT may therefore endow the enzyme with the promiscuity needed to recognize and reglucosylate its many different substrates and/or enable reglucosylation of N-linked glycans situated at variable distances from the site of misfold. 28739903 5 50 dep β-sandwiches 1074:1085 arg1 clasping 1095:1102 clasping 1095:1102 clasping 1095:1102 Here, crystal structures of a full-length eukaryotic UGGT reveal four thioredoxin-like (TRXL) domains arranged in a long arc that terminates in two β-sandwiches tightly clasping the glucosyltransferase domain. 28739903 4 51 theme glucose-accepting 866:882 arg1 glycan 893:898 a glucose-accepting N-linked glycan 864:898 a glucose-accepting N-linked glycan 864:898 Questions remain on how this single enzyme can flag misfolded glycoproteins of different sizes and shapes for ER retention and how it can span variable distances between the site of misfold and a glucose-accepting N-linked glycan on the same glycoprotein. 28739903 4 52 theme single 699:704 arg1 enzyme 706:711 this single enzyme 694:711 this single enzyme 694:711 Questions remain on how this single enzyme can flag misfolded glycoproteins of different sizes and shapes for ER retention and how it can span variable distances between the site of misfold and a glucose-accepting N-linked glycan on the same glycoprotein. 28739903 4 53 gly glycoprotein 912:923 arg1 glycoprotein 912:923 the same glycoprotein 903:923 the same glycoprotein 903:923 Questions remain on how this single enzyme can flag misfolded glycoproteins of different sizes and shapes for ER retention and how it can span variable distances between the site of misfold and a glucose-accepting N-linked glycan on the same glycoprotein. 28739903 4 54 theme glycan 893:898 arg1 glycan 893:898 a glucose-accepting N-linked glycan 864:898 a glucose-accepting N-linked glycan 864:898 Questions remain on how this single enzyme can flag misfolded glycoproteins of different sizes and shapes for ER retention and how it can span variable distances between the site of misfold and a glucose-accepting N-linked glycan on the same glycoprotein. 28739903 4 54 theme glycan 893:898 arg1 misfold 852:858 misfold 852:858 misfold 852:858 Questions remain on how this single enzyme can flag misfolded glycoproteins of different sizes and shapes for ER retention and how it can span variable distances between the site of misfold and a glucose-accepting N-linked glycan on the same glycoprotein. 28739903 4 54 theme glycan 893:898 arg1 site 844:847 the site 840:847 the site of misfold and a glucose-accepting N-linked glycan on the same glycoprotein 840:923 Questions remain on how this single enzyme can flag misfolded glycoproteins of different sizes and shapes for ER retention and how it can span variable distances between the site of misfold and a glucose-accepting N-linked glycan on the same glycoprotein. 28739903 8 55 theme UGGT 1510:1513 arg1 structure 1515:1523 the UGGT structure 1506:1523 the UGGT structure 1506:1523 Double cysteine point mutants that engineer extra interdomain disulfide bridges rigidify the UGGT structure and exhibit impaired activity. 28739903 9 56 theme glycans 1772:1778 arg1 reglucosylation 1744:1758 reglucosylation 1744:1758 reglucosylation of N-linked glycans situated at variable distances from the site of misfold 1744:1834 The intrinsic flexibility of the TRXL domains of UGGT may therefore endow the enzyme with the promiscuity needed to recognize and reglucosylate its many different substrates and/or enable reglucosylation of N-linked glycans situated at variable distances from the site of misfold. 28739903 3 57 theme sequence-based 627:640 arg1 prediction 658:667 sequence-based domain boundary prediction 627:667 sequence-based domain boundary prediction 627:667 UGGT has long resisted structural determination and sequence-based domain boundary prediction. 28739903 4 58 link N-linked 884:891 arg1 glycan 893:898 a glucose-accepting N-linked glycan 864:898 a glucose-accepting N-linked glycan 864:898 Questions remain on how this single enzyme can flag misfolded glycoproteins of different sizes and shapes for ER retention and how it can span variable distances between the site of misfold and a glucose-accepting N-linked glycan on the same glycoprotein. 28739903 8 59 theme impaired 1537:1544 arg1 activity 1546:1553 impaired activity 1537:1553 impaired activity 1537:1553 Double cysteine point mutants that engineer extra interdomain disulfide bridges rigidify the UGGT structure and exhibit impaired activity. 28739903 4 60 theme sizes 759:763 arg1 glycoproteins 732:744 misfolded glycoproteins 722:744 misfolded glycoproteins of different sizes and shapes for ER retention 722:791 Questions remain on how this single enzyme can flag misfolded glycoproteins of different sizes and shapes for ER retention and how it can span variable distances between the site of misfold and a glucose-accepting N-linked glycan on the same glycoprotein. 28739903 1 61 theme eukaryotic 150:159 arg1 pathway 171:177 the eukaryotic secretory pathway 146:177 the eukaryotic secretory pathway begin life in the endoplasmic reticulum (ER), where their folding is surveyed by the 170-kDa UDP-glucose 146:282 Glycoproteins traversing the eukaryotic secretory pathway begin life in the endoplasmic reticulum (ER), where their folding is surveyed by the 170-kDa UDP-glucose:glycoprotein glucosyltransferase (UGGT). 28739903 9 62 from site 1820:1823 arg1 distances 1801:1809 variable distances 1792:1809 variable distances from the site of misfold 1792:1834 The intrinsic flexibility of the TRXL domains of UGGT may therefore endow the enzyme with the promiscuity needed to recognize and reglucosylate its many different substrates and/or enable reglucosylation of N-linked glycans situated at variable distances from the site of misfold. 28739903 7 63 theme domains 1408:1414 arg1 flexibility 1384:1394 interdomain flexibility 1372:1394 interdomain flexibility of the TRXL domains 1372:1414 In addition to the crystal structures, a 15-Å cryo-EM reconstruction reveals interdomain flexibility of the TRXL domains. 28739903 4 64 theme shapes 769:774 arg1 glycoproteins 732:744 misfolded glycoproteins 722:744 misfolded glycoproteins of different sizes and shapes for ER retention 722:791 Questions remain on how this single enzyme can flag misfolded glycoproteins of different sizes and shapes for ER retention and how it can span variable distances between the site of misfold and a glucose-accepting N-linked glycan on the same glycoprotein. 28739903 3 65 theme boundary 649:656 arg1 prediction 658:667 sequence-based domain boundary prediction 627:667 sequence-based domain boundary prediction 627:667 UGGT has long resisted structural determination and sequence-based domain boundary prediction. 28739903 6 66 theme TRXL 1228:1231 arg1 domain 1233:1238 the fourth TRXL domain 1217:1238 the fourth TRXL domain 1217:1238 The fold of the molecule is topologically complex, with the first β-sandwich and the fourth TRXL domain being encoded by nonconsecutive stretches of sequence. 28739903 1 67 dep Glycoproteins 121:133 arg1 glucosyltransferase 297:315 glycoprotein glucosyltransferase 284:315 Glycoproteins traversing the eukaryotic secretory pathway begin life in the endoplasmic reticulum (ER), where their folding is surveyed by the 170-kDa UDP-glucose:glycoprotein glucosyltransferase (UGGT). 121:323 Glycoproteins traversing the eukaryotic secretory pathway begin life in the endoplasmic reticulum (ER), where their folding is surveyed by the 170-kDa UDP-glucose:glycoprotein glucosyltransferase (UGGT). 28739903 1 67 dep Glycoproteins 121:133 arg1 UGGT 318:321 UGGT 318:321 UGGT 318:321 Glycoproteins traversing the eukaryotic secretory pathway begin life in the endoplasmic reticulum (ER), where their folding is surveyed by the 170-kDa UDP-glucose:glycoprotein glucosyltransferase (UGGT). 28739903 0 68 theme glycoprotein 86:97 arg1 checkpoint 109:118 the eukaryotic glycoprotein secretion checkpoint 71:118 the eukaryotic glycoprotein secretion checkpoint 71:118 Interdomain conformational flexibility underpins the activity of UGGT, the eukaryotic glycoprotein secretion checkpoint. 28739903 0 68 theme glycoprotein 86:97 arg1 activity 53:60 the activity 49:60 the activity of UGGT 49:68 Interdomain conformational flexibility underpins the activity of UGGT, the eukaryotic glycoprotein secretion checkpoint. 28739903 5 69 theme crystal 932:938 arg1 structures 940:949 crystal structures 932:949 crystal structures of a full-length eukaryotic UGGT 932:982 Here, crystal structures of a full-length eukaryotic UGGT reveal four thioredoxin-like (TRXL) domains arranged in a long arc that terminates in two β-sandwiches tightly clasping the glucosyltransferase domain. 28739903 2 70 theme associated 506:515 arg1 chaperones 517:526 associated chaperones 506:526 associated chaperones 506:526 The enzyme acts as the single glycoprotein folding quality control checkpoint: it selectively reglucosylates misfolded glycoproteins, promotes their association with ER lectins and associated chaperones, and prevents premature secretion from the ER. 28739903 2 71 gly glycoproteins 444:456 arg1 glycoproteins 444:456 misfolded glycoproteins 434:456 misfolded glycoproteins 434:456 The enzyme acts as the single glycoprotein folding quality control checkpoint: it selectively reglucosylates misfolded glycoproteins, promotes their association with ER lectins and associated chaperones, and prevents premature secretion from the ER. 28739903 9 72 theme UGGT 1605:1608 arg1 UGGT 1605:1608 UGGT 1605:1608 UGGT 1605:1608 The intrinsic flexibility of the TRXL domains of UGGT may therefore endow the enzyme with the promiscuity needed to recognize and reglucosylate its many different substrates and/or enable reglucosylation of N-linked glycans situated at variable distances from the site of misfold. 28739903 9 72 theme UGGT 1605:1608 arg1 domains 1594:1600 the TRXL domains 1585:1600 the TRXL domains of UGGT 1585:1608 The intrinsic flexibility of the TRXL domains of UGGT may therefore endow the enzyme with the promiscuity needed to recognize and reglucosylate its many different substrates and/or enable reglucosylation of N-linked glycans situated at variable distances from the site of misfold. 28739903 6 73 theme molecule 1152:1159 arg1 fold 1140:1143 The fold 1136:1143 The fold of the molecule 1136:1159 The fold of the molecule is topologically complex, with the first β-sandwich and the fourth TRXL domain being encoded by nonconsecutive stretches of sequence. 28739903 6 73 theme molecule 1152:1159 arg1 complex 1178:1184 complex 1178:1184 complex 1178:1184 The fold of the molecule is topologically complex, with the first β-sandwich and the fourth TRXL domain being encoded by nonconsecutive stretches of sequence. 28739903 7 74 theme interdomain 1372:1382 arg1 flexibility 1384:1394 interdomain flexibility 1372:1394 interdomain flexibility of the TRXL domains 1372:1414 In addition to the crystal structures, a 15-Å cryo-EM reconstruction reveals interdomain flexibility of the TRXL domains. 28739903 0 75 theme conformational 12:25 arg1 flexibility 27:37 Interdomain conformational flexibility 0:37 Interdomain conformational flexibility 0:37 Interdomain conformational flexibility underpins the activity of UGGT, the eukaryotic glycoprotein secretion checkpoint. 28739903 5 76 theme UGGT 979:982 arg1 structures 940:949 crystal structures 932:949 crystal structures of a full-length eukaryotic UGGT 932:982 Here, crystal structures of a full-length eukaryotic UGGT reveal four thioredoxin-like (TRXL) domains arranged in a long arc that terminates in two β-sandwiches tightly clasping the glucosyltransferase domain. 28739903 4 77 theme ER 780:781 arg1 retention 783:791 ER retention 780:791 ER retention 780:791 Questions remain on how this single enzyme can flag misfolded glycoproteins of different sizes and shapes for ER retention and how it can span variable distances between the site of misfold and a glucose-accepting N-linked glycan on the same glycoprotein. 28739903 2 78 theme control 384:390 arg1 enzyme 329:334 The enzyme 325:334 The enzyme 325:334 The enzyme acts as the single glycoprotein folding quality control checkpoint: it selectively reglucosylates misfolded glycoproteins, promotes their association with ER lectins and associated chaperones, and prevents premature secretion from the ER. 28739903 2 78 theme control 384:390 arg1 checkpoint 392:401 the single glycoprotein folding quality control checkpoint 344:401 the single glycoprotein folding quality control checkpoint 344:401 The enzyme acts as the single glycoprotein folding quality control checkpoint: it selectively reglucosylates misfolded glycoproteins, promotes their association with ER lectins and associated chaperones, and prevents premature secretion from the ER. 28739903 1 79 theme glycoprotein 284:295 arg1 glucosyltransferase 297:315 glycoprotein glucosyltransferase 284:315 Glycoproteins traversing the eukaryotic secretory pathway begin life in the endoplasmic reticulum (ER), where their folding is surveyed by the 170-kDa UDP-glucose:glycoprotein glucosyltransferase (UGGT). 121:323 Glycoproteins traversing the eukaryotic secretory pathway begin life in the endoplasmic reticulum (ER), where their folding is surveyed by the 170-kDa UDP-glucose:glycoprotein glucosyltransferase (UGGT). 28739903 1 79 theme glycoprotein 284:295 arg1 UGGT 318:321 UGGT 318:321 UGGT 318:321 Glycoproteins traversing the eukaryotic secretory pathway begin life in the endoplasmic reticulum (ER), where their folding is surveyed by the 170-kDa UDP-glucose:glycoprotein glucosyltransferase (UGGT). 28739903 7 80 theme 15-Å 1336:1339 arg1 reconstruction 1349:1362 a 15-Å cryo-EM reconstruction 1334:1362 a 15-Å cryo-EM reconstruction 1334:1362 In addition to the crystal structures, a 15-Å cryo-EM reconstruction reveals interdomain flexibility of the TRXL domains. 28739903 8 81 theme cysteine 1424:1431 arg1 mutants 1439:1445 Double cysteine point mutants 1417:1445 Double cysteine point mutants that engineer extra interdomain disulfide bridges 1417:1495 Double cysteine point mutants that engineer extra interdomain disulfide bridges rigidify the UGGT structure and exhibit impaired activity. 28739903 2 82 theme misfolded 434:442 arg1 glycoproteins 444:456 misfolded glycoproteins 434:456 misfolded glycoproteins 434:456 The enzyme acts as the single glycoprotein folding quality control checkpoint: it selectively reglucosylates misfolded glycoproteins, promotes their association with ER lectins and associated chaperones, and prevents premature secretion from the ER. 28739903 9 83 link N-linked 1763:1770 arg1 glycans 1772:1778 N-linked glycans 1763:1778 N-linked glycans situated at variable distances from the site of misfold 1763:1834 The intrinsic flexibility of the TRXL domains of UGGT may therefore endow the enzyme with the promiscuity needed to recognize and reglucosylate its many different substrates and/or enable reglucosylation of N-linked glycans situated at variable distances from the site of misfold. 28739903 2 84 gly glycoprotein 355:366 arg1 glycoprotein 355:366 the single glycoprotein folding quality control checkpoint 344:401 the single glycoprotein folding quality control checkpoint 344:401 The enzyme acts as the single glycoprotein folding quality control checkpoint: it selectively reglucosylates misfolded glycoproteins, promotes their association with ER lectins and associated chaperones, and prevents premature secretion from the ER. 28739903 0 85 theme UGGT 65:68 arg1 activity 53:60 the activity 49:60 the activity of UGGT 49:68 Interdomain conformational flexibility underpins the activity of UGGT, the eukaryotic glycoprotein secretion checkpoint. 28739903 0 85 theme UGGT 65:68 arg1 checkpoint 109:118 the eukaryotic glycoprotein secretion checkpoint 71:118 the eukaryotic glycoprotein secretion checkpoint 71:118 Interdomain conformational flexibility underpins the activity of UGGT, the eukaryotic glycoprotein secretion checkpoint. 28739903 7 86 theme crystal 1314:1320 arg1 structures 1322:1331 the crystal structures 1310:1331 the crystal structures 1310:1331 In addition to the crystal structures, a 15-Å cryo-EM reconstruction reveals interdomain flexibility of the TRXL domains. 28739903 9 87 theme many 1704:1707 arg1 substrates 1719:1728 its many different substrates 1700:1728 its many different substrates 1700:1728 The intrinsic flexibility of the TRXL domains of UGGT may therefore endow the enzyme with the promiscuity needed to recognize and reglucosylate its many different substrates and/or enable reglucosylation of N-linked glycans situated at variable distances from the site of misfold. 28739903 2 88 from ER 571:572 arg1 secretion 552:560 premature secretion 542:560 premature secretion from the ER 542:572 The enzyme acts as the single glycoprotein folding quality control checkpoint: it selectively reglucosylates misfolded glycoproteins, promotes their association with ER lectins and associated chaperones, and prevents premature secretion from the ER. 28739903 7 89 dep structures 1322:1331 arg1 addition 1298:1305 addition 1298:1305 addition 1298:1305 In addition to the crystal structures, a 15-Å cryo-EM reconstruction reveals interdomain flexibility of the TRXL domains. 28739903 8 90 theme interdomain 1467:1477 arg1 bridges 1489:1495 extra interdomain disulfide bridges 1461:1495 extra interdomain disulfide bridges 1461:1495 Double cysteine point mutants that engineer extra interdomain disulfide bridges rigidify the UGGT structure and exhibit impaired activity. 28739903 2 91 theme folding 368:374 arg1 enzyme 329:334 The enzyme 325:334 The enzyme 325:334 The enzyme acts as the single glycoprotein folding quality control checkpoint: it selectively reglucosylates misfolded glycoproteins, promotes their association with ER lectins and associated chaperones, and prevents premature secretion from the ER. 28739903 2 91 theme folding 368:374 arg1 checkpoint 392:401 the single glycoprotein folding quality control checkpoint 344:401 the single glycoprotein folding quality control checkpoint 344:401 The enzyme acts as the single glycoprotein folding quality control checkpoint: it selectively reglucosylates misfolded glycoproteins, promotes their association with ER lectins and associated chaperones, and prevents premature secretion from the ER. 28159791 5 0 dep polysaccharides 1410:1424 arg1 lipids 1470:1475 lipids 1470:1475 mostly polysaccharides and saturated aliphatic chains (most likely lipids) 1403:1476 We found a low organic carbon content in the stalks (∼0.3 wt%), with mostly polysaccharides and saturated aliphatic chains (most likely lipids). 28159791 2 1 theme Fe 600:601 arg1 oxidizers 607:615 marine microaerophilic Fe(II) oxidizers 577:615 marine microaerophilic Fe(II) oxidizers 577:615 Isolates originating from freshwater habitats are all members of the Betaproteobacteria, while isolates from marine habitats belong almost exclusively to the Zetaproteobacteria So far, only a few isolates of marine microaerophilic Fe(II) oxidizers have been described, all of which are obligate microaerophilic Fe(II) oxidizers and have been thought to be restricted to Fe-rich systems. 28159791 11 2 theme possible 2508:2515 arg1 habitats 2517:2524 possible habitats 2508:2524 possible habitats in which Zetaproteobacteria can exist 2508:2562 This increases the knowledge about possible habitats in which Zetaproteobacteria can exist. 28159791 12 3 with environments 2790:2801 arg1 concentrations 2816:2829 high Fe concentrations 2808:2829 high Fe concentrations 2808:2829 Furthermore, we show that the physiology and the typical organo-mineral structures (twisted stalks) that are produced by the isolates do not notably differ from the physiology and the cell-mineral structures of isolates from environments with high Fe concentrations. 28159791 2 4 theme marine 577:582 arg1 oxidizers 607:615 marine microaerophilic Fe(II) oxidizers 577:615 marine microaerophilic Fe(II) oxidizers 577:615 Isolates originating from freshwater habitats are all members of the Betaproteobacteria, while isolates from marine habitats belong almost exclusively to the Zetaproteobacteria So far, only a few isolates of marine microaerophilic Fe(II) oxidizers have been described, all of which are obligate microaerophilic Fe(II) oxidizers and have been thought to be restricted to Fe-rich systems. 28159791 8 5 located found 1836:1840 arg2 oxidizers 1725:1733 obligate microaerophilic Fe(II) oxidizers 1693:1733 obligate microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria group 1693:1775 Our findings show that obligate microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria group are not restricted to Fe-rich environments but can also be found in low-Fe marine environments, which increases their overall importance for the global biogeochemical Fe cycle.IMPORTANCE So far, only a few isolates of benthic marine microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria exist, and most isolates were obtained from habitats containing elevated Fe concentrations. 28159791 8 5 located found 1836:1840 arg1 environments 1859:1870 low-Fe marine environments 1845:1870 low-Fe marine environments 1845:1870 Our findings show that obligate microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria group are not restricted to Fe-rich environments but can also be found in low-Fe marine environments, which increases their overall importance for the global biogeochemical Fe cycle.IMPORTANCE So far, only a few isolates of benthic marine microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria exist, and most isolates were obtained from habitats containing elevated Fe concentrations. 28159791 4 6 theme Fe 1244:1245 arg1 oxidizers 1251:1259 obligate microaerophilic Fe(II) oxidizers 1219:1259 obligate microaerophilic Fe(II) oxidizers 1219:1259 The two novel Zetaproteobacteria share characteristic physiological properties of the Zetaproteobacteria group, even though they come from low-Fe environments: the isolates are obligate microaerophilic Fe(II) oxidizers and, like most isolated Zetaproteobacteria, they produce twisted stalks. 28159791 4 6 theme Fe 1244:1245 arg1 isolates 1206:1213 the isolates 1202:1213 the isolates 1202:1213 The two novel Zetaproteobacteria share characteristic physiological properties of the Zetaproteobacteria group, even though they come from low-Fe environments: the isolates are obligate microaerophilic Fe(II) oxidizers and, like most isolated Zetaproteobacteria, they produce twisted stalks. 28159791 4 7 theme characteristic 1081:1094 arg1 properties 1110:1119 characteristic physiological properties 1081:1119 characteristic physiological properties of the Zetaproteobacteria group 1081:1151 The two novel Zetaproteobacteria share characteristic physiological properties of the Zetaproteobacteria group, even though they come from low-Fe environments: the isolates are obligate microaerophilic Fe(II) oxidizers and, like most isolated Zetaproteobacteria, they produce twisted stalks. 28159791 5 8 theme organic 1349:1355 arg1 content 1364:1370 a low organic carbon content 1343:1370 a low organic carbon content 1343:1370 We found a low organic carbon content in the stalks (∼0.3 wt%), with mostly polysaccharides and saturated aliphatic chains (most likely lipids). 28159791 9 9 theme high 2264:2267 arg1 concentrations 2272:2285 high Fe concentrations 2264:2285 high Fe concentrations 2264:2285 Consequently, it was thought that these microorganisms are important mainly in habitats with high Fe concentrations. 28159791 3 10 theme Zetaproteobacteria 833:850 arg1 isolates 781:788 two new isolates 773:788 two new isolates of marine microaerophilic Fe(II)-oxidizing Zetaproteobacteria that originate from typical coastal marine sediments containing only low Fe concentrations (2 to 11 mg of total Fe/g of sediment [dry weight]; 70 to 100 μM dissolved Fe2+ in the porewater) 773:1039 Here, we present two new isolates of marine microaerophilic Fe(II)-oxidizing Zetaproteobacteria that originate from typical coastal marine sediments containing only low Fe concentrations (2 to 11 mg of total Fe/g of sediment [dry weight]; 70 to 100 μM dissolved Fe2+ in the porewater). 28159791 2 11 theme oxidizers 607:615 arg1 isolates 565:572 only a few isolates 554:572 only a few isolates of marine microaerophilic Fe(II) oxidizers 554:615 Isolates originating from freshwater habitats are all members of the Betaproteobacteria, while isolates from marine habitats belong almost exclusively to the Zetaproteobacteria So far, only a few isolates of marine microaerophilic Fe(II) oxidizers have been described, all of which are obligate microaerophilic Fe(II) oxidizers and have been thought to be restricted to Fe-rich systems. 28159791 8 12 theme Zetaproteobacteria 1752:1769 arg1 group 1771:1775 the Zetaproteobacteria group 1748:1775 the Zetaproteobacteria group 1748:1775 Our findings show that obligate microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria group are not restricted to Fe-rich environments but can also be found in low-Fe marine environments, which increases their overall importance for the global biogeochemical Fe cycle.IMPORTANCE So far, only a few isolates of benthic marine microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria exist, and most isolates were obtained from habitats containing elevated Fe concentrations. 28159791 12 13 theme twisted 2649:2655 arg1 structures 2637:2646 the typical organo-mineral structures 2610:2646 the typical organo-mineral structures (twisted stalks) that are produced by the isolates 2610:2697 Furthermore, we show that the physiology and the typical organo-mineral structures (twisted stalks) that are produced by the isolates do not notably differ from the physiology and the cell-mineral structures of isolates from environments with high Fe concentrations. 28159791 12 13 theme twisted 2649:2655 arg1 stalks 2657:2662 twisted stalks 2649:2662 twisted stalks 2649:2662 Furthermore, we show that the physiology and the typical organo-mineral structures (twisted stalks) that are produced by the isolates do not notably differ from the physiology and the cell-mineral structures of isolates from environments with high Fe concentrations. 28159791 3 14 theme sediment 972:979 arg1 weight 986:991 sediment [dry weight 972:991 sediment [dry weight 972:991 Here, we present two new isolates of marine microaerophilic Fe(II)-oxidizing Zetaproteobacteria that originate from typical coastal marine sediments containing only low Fe concentrations (2 to 11 mg of total Fe/g of sediment [dry weight]; 70 to 100 μM dissolved Fe2+ in the porewater). 28159791 9 15 with habitats 2250:2257 arg1 concentrations 2272:2285 high Fe concentrations 2264:2285 high Fe concentrations 2264:2285 Consequently, it was thought that these microorganisms are important mainly in habitats with high Fe concentrations. 28159791 3 16 theme Fe/g 964:967 arg1 mg 952:953 2 to 11 mg 944:953 2 to 11 mg of total Fe/g of sediment [dry weight 944:991 Here, we present two new isolates of marine microaerophilic Fe(II)-oxidizing Zetaproteobacteria that originate from typical coastal marine sediments containing only low Fe concentrations (2 to 11 mg of total Fe/g of sediment [dry weight]; 70 to 100 μM dissolved Fe2+ in the porewater). 28159791 10 17 theme marine 2408:2413 arg1 sediments 2415:2423 typical coastal marine sediments 2392:2423 typical coastal marine sediments that do not contain elevated Fe concentrations 2392:2470 The two novel isolates of Zetaproteobacteria that are presented in the present study were isolated from typical coastal marine sediments that do not contain elevated Fe concentrations. 28159791 4 18 theme twisted 1318:1324 arg1 stalks 1326:1331 twisted stalks 1318:1331 twisted stalks 1318:1331 The two novel Zetaproteobacteria share characteristic physiological properties of the Zetaproteobacteria group, even though they come from low-Fe environments: the isolates are obligate microaerophilic Fe(II) oxidizers and, like most isolated Zetaproteobacteria, they produce twisted stalks. 28159791 12 19 dep physiology 2730:2739 arg1 the 2726:2728 the 2726:2728 the 2726:2728 Furthermore, we show that the physiology and the typical organo-mineral structures (twisted stalks) that are produced by the isolates do not notably differ from the physiology and the cell-mineral structures of isolates from environments with high Fe concentrations. 28159791 12 20 theme typical 2614:2620 arg1 structures 2637:2646 the typical organo-mineral structures 2610:2646 the typical organo-mineral structures (twisted stalks) that are produced by the isolates 2610:2697 Furthermore, we show that the physiology and the typical organo-mineral structures (twisted stalks) that are produced by the isolates do not notably differ from the physiology and the cell-mineral structures of isolates from environments with high Fe concentrations. 28159791 12 20 theme typical 2614:2620 arg1 stalks 2657:2662 twisted stalks 2649:2662 twisted stalks 2649:2662 Furthermore, we show that the physiology and the typical organo-mineral structures (twisted stalks) that are produced by the isolates do not notably differ from the physiology and the cell-mineral structures of isolates from environments with high Fe concentrations. 28159791 9 21 from important 2230:2238 arg1 habitats 2250:2257 habitats 2250:2257 habitats with high Fe concentrations 2250:2285 Consequently, it was thought that these microorganisms are important mainly in habitats with high Fe concentrations. 28159791 10 22 theme typical 2392:2398 arg1 sediments 2415:2423 typical coastal marine sediments 2392:2423 typical coastal marine sediments that do not contain elevated Fe concentrations 2392:2470 The two novel isolates of Zetaproteobacteria that are presented in the present study were isolated from typical coastal marine sediments that do not contain elevated Fe concentrations. 28159791 8 23 theme Fe-rich 1799:1805 arg1 environments 1807:1818 Fe-rich environments 1799:1818 Fe-rich environments 1799:1818 Our findings show that obligate microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria group are not restricted to Fe-rich environments but can also be found in low-Fe marine environments, which increases their overall importance for the global biogeochemical Fe cycle.IMPORTANCE So far, only a few isolates of benthic marine microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria exist, and most isolates were obtained from habitats containing elevated Fe concentrations. 28159791 2 24 from habitats 485:492 arg1 isolates 464:471 isolates 464:471 isolates from marine habitats 464:492 Isolates originating from freshwater habitats are all members of the Betaproteobacteria, while isolates from marine habitats belong almost exclusively to the Zetaproteobacteria So far, only a few isolates of marine microaerophilic Fe(II) oxidizers have been described, all of which are obligate microaerophilic Fe(II) oxidizers and have been thought to be restricted to Fe-rich systems. 28159791 2 25 theme Fe 680:681 arg1 which 645:649 which 645:649 which 645:649 Isolates originating from freshwater habitats are all members of the Betaproteobacteria, while isolates from marine habitats belong almost exclusively to the Zetaproteobacteria So far, only a few isolates of marine microaerophilic Fe(II) oxidizers have been described, all of which are obligate microaerophilic Fe(II) oxidizers and have been thought to be restricted to Fe-rich systems. 28159791 2 25 theme Fe 680:681 arg1 oxidizers 687:695 obligate microaerophilic Fe(II) oxidizers 655:695 obligate microaerophilic Fe(II) oxidizers 655:695 Isolates originating from freshwater habitats are all members of the Betaproteobacteria, while isolates from marine habitats belong almost exclusively to the Zetaproteobacteria So far, only a few isolates of marine microaerophilic Fe(II) oxidizers have been described, all of which are obligate microaerophilic Fe(II) oxidizers and have been thought to be restricted to Fe-rich systems. 28159791 2 25 theme Fe 680:681 arg1 all 638:640 all 638:640 all 638:640 Isolates originating from freshwater habitats are all members of the Betaproteobacteria, while isolates from marine habitats belong almost exclusively to the Zetaproteobacteria So far, only a few isolates of marine microaerophilic Fe(II) oxidizers have been described, all of which are obligate microaerophilic Fe(II) oxidizers and have been thought to be restricted to Fe-rich systems. 28159791 0 26 theme Stalks 143:148 arg1 Composition 114:124 Composition 114:124 Composition 114:124 Microaerophilic Fe(II)-Oxidizing Zetaproteobacteria Isolated from Low-Fe Marine Coastal Sediments: Physiology and Composition of Their Twisted Stalks. 28159791 0 26 theme Stalks 143:148 arg1 Physiology 99:108 Physiology 99:108 Physiology 99:108 Microaerophilic Fe(II)-Oxidizing Zetaproteobacteria Isolated from Low-Fe Marine Coastal Sediments: Physiology and Composition of Their Twisted Stalks. 28159791 0 26 theme Stalks 143:148 arg1 Sediments 88:96 Low-Fe Marine Coastal Sediments 66:96 Low-Fe Marine Coastal Sediments: Physiology and Composition of Their Twisted Stalks 66:148 Microaerophilic Fe(II)-Oxidizing Zetaproteobacteria Isolated from Low-Fe Marine Coastal Sediments: Physiology and Composition of Their Twisted Stalks. 28159791 3 27 theme marine 793:798 arg1 Zetaproteobacteria 833:850 marine microaerophilic Fe(II)-oxidizing Zetaproteobacteria 793:850 marine microaerophilic Fe(II)-oxidizing Zetaproteobacteria 793:850 Here, we present two new isolates of marine microaerophilic Fe(II)-oxidizing Zetaproteobacteria that originate from typical coastal marine sediments containing only low Fe concentrations (2 to 11 mg of total Fe/g of sediment [dry weight]; 70 to 100 μM dissolved Fe2+ in the porewater). 28159791 2 28 theme obligate 655:662 arg1 which 645:649 which 645:649 which 645:649 Isolates originating from freshwater habitats are all members of the Betaproteobacteria, while isolates from marine habitats belong almost exclusively to the Zetaproteobacteria So far, only a few isolates of marine microaerophilic Fe(II) oxidizers have been described, all of which are obligate microaerophilic Fe(II) oxidizers and have been thought to be restricted to Fe-rich systems. 28159791 2 28 theme obligate 655:662 arg1 oxidizers 687:695 obligate microaerophilic Fe(II) oxidizers 655:695 obligate microaerophilic Fe(II) oxidizers 655:695 Isolates originating from freshwater habitats are all members of the Betaproteobacteria, while isolates from marine habitats belong almost exclusively to the Zetaproteobacteria So far, only a few isolates of marine microaerophilic Fe(II) oxidizers have been described, all of which are obligate microaerophilic Fe(II) oxidizers and have been thought to be restricted to Fe-rich systems. 28159791 2 28 theme obligate 655:662 arg1 all 638:640 all 638:640 all 638:640 Isolates originating from freshwater habitats are all members of the Betaproteobacteria, while isolates from marine habitats belong almost exclusively to the Zetaproteobacteria So far, only a few isolates of marine microaerophilic Fe(II) oxidizers have been described, all of which are obligate microaerophilic Fe(II) oxidizers and have been thought to be restricted to Fe-rich systems. 28159791 13 29 theme trace 2909:2913 arg1 metals 2915:2920 trace metals 2909:2920 trace metals 2909:2920 We also showed that the organo-mineral structures can function as a sink for trace metals. 28159791 12 30 theme cell-mineral 2749:2760 arg1 structures 2762:2771 the cell-mineral structures 2745:2771 the cell-mineral structures 2745:2771 Furthermore, we show that the physiology and the typical organo-mineral structures (twisted stalks) that are produced by the isolates do not notably differ from the physiology and the cell-mineral structures of isolates from environments with high Fe concentrations. 28159791 8 31 theme elevated 2143:2150 arg1 concentrations 2155:2168 elevated Fe concentrations 2143:2168 elevated Fe concentrations 2143:2168 Our findings show that obligate microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria group are not restricted to Fe-rich environments but can also be found in low-Fe marine environments, which increases their overall importance for the global biogeochemical Fe cycle.IMPORTANCE So far, only a few isolates of benthic marine microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria exist, and most isolates were obtained from habitats containing elevated Fe concentrations. 28159791 1 32 theme mineral 304:310 arg1 structures 312:321 Fe mineral structures 301:321 Fe mineral structures 301:321 Microaerophilic Fe(II) oxidizers are commonly found in habitats containing elevated Fe(II) and low O2 concentrations and often produce characteristic Fe mineral structures, so-called twisted stalks or tubular sheaths. 28159791 2 33 theme marine 478:483 arg1 habitats 485:492 marine habitats 478:492 marine habitats 478:492 Isolates originating from freshwater habitats are all members of the Betaproteobacteria, while isolates from marine habitats belong almost exclusively to the Zetaproteobacteria So far, only a few isolates of marine microaerophilic Fe(II) oxidizers have been described, all of which are obligate microaerophilic Fe(II) oxidizers and have been thought to be restricted to Fe-rich systems. 28159791 10 34 theme elevated 2445:2452 arg1 concentrations 2457:2470 elevated Fe concentrations 2445:2470 elevated Fe concentrations 2445:2470 The two novel isolates of Zetaproteobacteria that are presented in the present study were isolated from typical coastal marine sediments that do not contain elevated Fe concentrations. 28159791 0 35 theme Marine 73:78 arg1 Composition 114:124 Composition 114:124 Composition 114:124 Microaerophilic Fe(II)-Oxidizing Zetaproteobacteria Isolated from Low-Fe Marine Coastal Sediments: Physiology and Composition of Their Twisted Stalks. 28159791 0 35 theme Marine 73:78 arg1 Physiology 99:108 Physiology 99:108 Physiology 99:108 Microaerophilic Fe(II)-Oxidizing Zetaproteobacteria Isolated from Low-Fe Marine Coastal Sediments: Physiology and Composition of Their Twisted Stalks. 28159791 0 35 theme Marine 73:78 arg1 Sediments 88:96 Low-Fe Marine Coastal Sediments 66:96 Low-Fe Marine Coastal Sediments: Physiology and Composition of Their Twisted Stalks 66:148 Microaerophilic Fe(II)-Oxidizing Zetaproteobacteria Isolated from Low-Fe Marine Coastal Sediments: Physiology and Composition of Their Twisted Stalks. 28159791 1 36 theme Fe 167:168 arg1 oxidizers 174:182 Microaerophilic Fe(II) oxidizers 151:182 Microaerophilic Fe(II) oxidizers 151:182 Microaerophilic Fe(II) oxidizers are commonly found in habitats containing elevated Fe(II) and low O2 concentrations and often produce characteristic Fe mineral structures, so-called twisted stalks or tubular sheaths. 28159791 3 37 theme Fe 816:817 arg1 Zetaproteobacteria 833:850 marine microaerophilic Fe(II)-oxidizing Zetaproteobacteria 793:850 marine microaerophilic Fe(II)-oxidizing Zetaproteobacteria 793:850 Here, we present two new isolates of marine microaerophilic Fe(II)-oxidizing Zetaproteobacteria that originate from typical coastal marine sediments containing only low Fe concentrations (2 to 11 mg of total Fe/g of sediment [dry weight]; 70 to 100 μM dissolved Fe2+ in the porewater). 28159791 3 38 contain containing 905:914 arg1 sediments 895:903 typical coastal marine sediments 872:903 typical coastal marine sediments containing only low Fe concentrations (2 to 11 mg of total Fe/g of sediment [dry weight]; 70 to 100 μM dissolved Fe2+ in the porewater) 872:1039 Here, we present two new isolates of marine microaerophilic Fe(II)-oxidizing Zetaproteobacteria that originate from typical coastal marine sediments containing only low Fe concentrations (2 to 11 mg of total Fe/g of sediment [dry weight]; 70 to 100 μM dissolved Fe2+ in the porewater). 28159791 3 38 contain containing 905:914 arg2 concentrations 928:941 only low Fe concentrations 916:941 only low Fe concentrations (2 to 11 mg of total Fe/g of sediment [dry weight]; 70 to 100 μM dissolved Fe2+ in the porewater) 916:1039 Here, we present two new isolates of marine microaerophilic Fe(II)-oxidizing Zetaproteobacteria that originate from typical coastal marine sediments containing only low Fe concentrations (2 to 11 mg of total Fe/g of sediment [dry weight]; 70 to 100 μM dissolved Fe2+ in the porewater). 28159791 5 39 theme wt 1392:1393 arg1 stalks 1379:1384 the stalks 1375:1384 the stalks (∼0.3 wt%) 1375:1395 We found a low organic carbon content in the stalks (∼0.3 wt%), with mostly polysaccharides and saturated aliphatic chains (most likely lipids). 28159791 5 39 theme wt 1392:1393 arg1 % 1394:1394 ∼0.3 wt% 1387:1394 ∼0.3 wt% 1387:1394 We found a low organic carbon content in the stalks (∼0.3 wt%), with mostly polysaccharides and saturated aliphatic chains (most likely lipids). 28159791 1 40 theme twisted 334:340 arg1 stalks 342:347 so-called twisted stalks 324:347 so-called twisted stalks 324:347 Microaerophilic Fe(II) oxidizers are commonly found in habitats containing elevated Fe(II) and low O2 concentrations and often produce characteristic Fe mineral structures, so-called twisted stalks or tubular sheaths. 28159791 3 41 theme weight 986:991 arg1 Fe/g 964:967 total Fe/g 958:967 total Fe/g of sediment [dry weight 958:991 Here, we present two new isolates of marine microaerophilic Fe(II)-oxidizing Zetaproteobacteria that originate from typical coastal marine sediments containing only low Fe concentrations (2 to 11 mg of total Fe/g of sediment [dry weight]; 70 to 100 μM dissolved Fe2+ in the porewater). 28159791 8 42 theme microaerophilic 1702:1716 arg1 II 1721:1722 II 1721:1722 II 1721:1722 Our findings show that obligate microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria group are not restricted to Fe-rich environments but can also be found in low-Fe marine environments, which increases their overall importance for the global biogeochemical Fe cycle.IMPORTANCE So far, only a few isolates of benthic marine microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria exist, and most isolates were obtained from habitats containing elevated Fe concentrations. 28159791 8 42 theme microaerophilic 1702:1716 arg1 Fe 1718:1719 microaerophilic Fe 1702:1719 obligate microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria group 1693:1775 Our findings show that obligate microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria group are not restricted to Fe-rich environments but can also be found in low-Fe marine environments, which increases their overall importance for the global biogeochemical Fe cycle.IMPORTANCE So far, only a few isolates of benthic marine microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria exist, and most isolates were obtained from habitats containing elevated Fe concentrations. 28159791 8 43 theme global 1922:1927 arg1 cycle.IMPORTANCE 1947:1962 the global biogeochemical Fe cycle.IMPORTANCE 1918:1962 the global biogeochemical Fe cycle.IMPORTANCE 1918:1962 Our findings show that obligate microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria group are not restricted to Fe-rich environments but can also be found in low-Fe marine environments, which increases their overall importance for the global biogeochemical Fe cycle.IMPORTANCE So far, only a few isolates of benthic marine microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria exist, and most isolates were obtained from habitats containing elevated Fe concentrations. 28159791 0 44 dep Sediments 88:96 arg1 Composition 114:124 Composition 114:124 Composition 114:124 Microaerophilic Fe(II)-Oxidizing Zetaproteobacteria Isolated from Low-Fe Marine Coastal Sediments: Physiology and Composition of Their Twisted Stalks. 28159791 0 44 dep Sediments 88:96 arg1 Physiology 99:108 Physiology 99:108 Physiology 99:108 Microaerophilic Fe(II)-Oxidizing Zetaproteobacteria Isolated from Low-Fe Marine Coastal Sediments: Physiology and Composition of Their Twisted Stalks. 28159791 0 44 dep Sediments 88:96 arg1 Sediments 88:96 Low-Fe Marine Coastal Sediments 66:96 Low-Fe Marine Coastal Sediments: Physiology and Composition of Their Twisted Stalks 66:148 Microaerophilic Fe(II)-Oxidizing Zetaproteobacteria Isolated from Low-Fe Marine Coastal Sediments: Physiology and Composition of Their Twisted Stalks. 28159791 3 45 theme -oxidizing 822:831 arg1 Zetaproteobacteria 833:850 marine microaerophilic Fe(II)-oxidizing Zetaproteobacteria 793:850 marine microaerophilic Fe(II)-oxidizing Zetaproteobacteria 793:850 Here, we present two new isolates of marine microaerophilic Fe(II)-oxidizing Zetaproteobacteria that originate from typical coastal marine sediments containing only low Fe concentrations (2 to 11 mg of total Fe/g of sediment [dry weight]; 70 to 100 μM dissolved Fe2+ in the porewater). 28159791 3 46 from concentrations 928:941 arg1 porewater 1030:1038 the porewater 1026:1038 the porewater 1026:1038 Here, we present two new isolates of marine microaerophilic Fe(II)-oxidizing Zetaproteobacteria that originate from typical coastal marine sediments containing only low Fe concentrations (2 to 11 mg of total Fe/g of sediment [dry weight]; 70 to 100 μM dissolved Fe2+ in the porewater). 28159791 0 47 theme Microaerophilic 0:14 arg1 Zetaproteobacteria 33:50 Microaerophilic Fe(II)-Oxidizing Zetaproteobacteria 0:50 Microaerophilic Fe(II)-Oxidizing Zetaproteobacteria 0:50 Microaerophilic Fe(II)-Oxidizing Zetaproteobacteria Isolated from Low-Fe Marine Coastal Sediments: Physiology and Composition of Their Twisted Stalks. 28159791 1 48 theme low 246:248 arg1 concentrations 253:266 low O2 concentrations 246:266 low O2 concentrations 246:266 Microaerophilic Fe(II) oxidizers are commonly found in habitats containing elevated Fe(II) and low O2 concentrations and often produce characteristic Fe mineral structures, so-called twisted stalks or tubular sheaths. 28159791 3 49 theme coastal 880:886 arg1 sediments 895:903 typical coastal marine sediments 872:903 typical coastal marine sediments containing only low Fe concentrations (2 to 11 mg of total Fe/g of sediment [dry weight]; 70 to 100 μM dissolved Fe2+ in the porewater) 872:1039 Here, we present two new isolates of marine microaerophilic Fe(II)-oxidizing Zetaproteobacteria that originate from typical coastal marine sediments containing only low Fe concentrations (2 to 11 mg of total Fe/g of sediment [dry weight]; 70 to 100 μM dissolved Fe2+ in the porewater). 28159791 13 50 theme organo-mineral 2856:2869 arg1 sink 2900:2903 a sink 2898:2903 a sink for trace metals 2898:2920 We also showed that the organo-mineral structures can function as a sink for trace metals. 28159791 13 50 theme organo-mineral 2856:2869 arg1 structures 2871:2880 the organo-mineral structures 2852:2880 the organo-mineral structures 2852:2880 We also showed that the organo-mineral structures can function as a sink for trace metals. 28159791 4 51 theme group 1147:1151 arg1 properties 1110:1119 characteristic physiological properties 1081:1119 characteristic physiological properties of the Zetaproteobacteria group 1081:1151 The two novel Zetaproteobacteria share characteristic physiological properties of the Zetaproteobacteria group, even though they come from low-Fe environments: the isolates are obligate microaerophilic Fe(II) oxidizers and, like most isolated Zetaproteobacteria, they produce twisted stalks. 28159791 5 52 theme saturated 1430:1438 arg1 chains 1450:1455 saturated aliphatic chains 1430:1455 saturated aliphatic chains 1430:1455 We found a low organic carbon content in the stalks (∼0.3 wt%), with mostly polysaccharides and saturated aliphatic chains (most likely lipids). 28159791 2 53 theme freshwater 395:404 arg1 habitats 406:413 freshwater habitats 395:413 freshwater habitats 395:413 Isolates originating from freshwater habitats are all members of the Betaproteobacteria, while isolates from marine habitats belong almost exclusively to the Zetaproteobacteria So far, only a few isolates of marine microaerophilic Fe(II) oxidizers have been described, all of which are obligate microaerophilic Fe(II) oxidizers and have been thought to be restricted to Fe-rich systems. 28159791 12 54 theme Fe 2813:2814 arg1 concentrations 2816:2829 high Fe concentrations 2808:2829 high Fe concentrations 2808:2829 Furthermore, we show that the physiology and the typical organo-mineral structures (twisted stalks) that are produced by the isolates do not notably differ from the physiology and the cell-mineral structures of isolates from environments with high Fe concentrations. 28159791 3 55 dep μM 1005:1006 arg1 Fe2+ 1018:1021 dissolved Fe2+ 1008:1021 only low Fe concentrations (2 to 11 mg of total Fe/g of sediment [dry weight]; 70 to 100 μM dissolved Fe2+ in the porewater) 916:1039 Here, we present two new isolates of marine microaerophilic Fe(II)-oxidizing Zetaproteobacteria that originate from typical coastal marine sediments containing only low Fe concentrations (2 to 11 mg of total Fe/g of sediment [dry weight]; 70 to 100 μM dissolved Fe2+ in the porewater). 28159791 1 56 theme characteristic 286:299 arg1 structures 312:321 Fe mineral structures 301:321 Fe mineral structures 301:321 Microaerophilic Fe(II) oxidizers are commonly found in habitats containing elevated Fe(II) and low O2 concentrations and often produce characteristic Fe mineral structures, so-called twisted stalks or tubular sheaths. 28159791 10 57 attach isolated 2378:2385 arg2 isolates 2302:2309 The two novel isolates 2288:2309 The two novel isolates of Zetaproteobacteria that are presented in the present study 2288:2371 The two novel isolates of Zetaproteobacteria that are presented in the present study were isolated from typical coastal marine sediments that do not contain elevated Fe concentrations. 28159791 10 57 attach isolated 2378:2385 arg1 sediments 2415:2423 typical coastal marine sediments 2392:2423 typical coastal marine sediments that do not contain elevated Fe concentrations 2392:2470 The two novel isolates of Zetaproteobacteria that are presented in the present study were isolated from typical coastal marine sediments that do not contain elevated Fe concentrations. 28159791 3 58 dep 11 949:950 arg1 to 946:947 to 946:947 to 946:947 Here, we present two new isolates of marine microaerophilic Fe(II)-oxidizing Zetaproteobacteria that originate from typical coastal marine sediments containing only low Fe concentrations (2 to 11 mg of total Fe/g of sediment [dry weight]; 70 to 100 μM dissolved Fe2+ in the porewater). 28159791 8 59 theme marine 2003:2008 arg1 II 2029:2030 II 2029:2030 II 2029:2030 Our findings show that obligate microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria group are not restricted to Fe-rich environments but can also be found in low-Fe marine environments, which increases their overall importance for the global biogeochemical Fe cycle.IMPORTANCE So far, only a few isolates of benthic marine microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria exist, and most isolates were obtained from habitats containing elevated Fe concentrations. 28159791 8 59 theme marine 2003:2008 arg1 Fe 2026:2027 benthic marine microaerophilic Fe 1995:2027 benthic marine microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria 1995:2077 Our findings show that obligate microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria group are not restricted to Fe-rich environments but can also be found in low-Fe marine environments, which increases their overall importance for the global biogeochemical Fe cycle.IMPORTANCE So far, only a few isolates of benthic marine microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria exist, and most isolates were obtained from habitats containing elevated Fe concentrations. 28159791 12 60 from environments 2790:2801 arg1 physiology 2730:2739 physiology 2730:2739 physiology 2730:2739 Furthermore, we show that the physiology and the typical organo-mineral structures (twisted stalks) that are produced by the isolates do not notably differ from the physiology and the cell-mineral structures of isolates from environments with high Fe concentrations. 28159791 12 60 from environments 2790:2801 arg1 isolates 2776:2783 isolates 2776:2783 isolates from environments with high Fe concentrations 2776:2829 Furthermore, we show that the physiology and the typical organo-mineral structures (twisted stalks) that are produced by the isolates do not notably differ from the physiology and the cell-mineral structures of isolates from environments with high Fe concentrations. 28159791 12 60 from environments 2790:2801 arg1 structures 2762:2771 the cell-mineral structures 2745:2771 the cell-mineral structures 2745:2771 Furthermore, we show that the physiology and the typical organo-mineral structures (twisted stalks) that are produced by the isolates do not notably differ from the physiology and the cell-mineral structures of isolates from environments with high Fe concentrations. 28159791 1 61 theme elevated 226:233 arg1 II 238:239 II 238:239 II 238:239 Microaerophilic Fe(II) oxidizers are commonly found in habitats containing elevated Fe(II) and low O2 concentrations and often produce characteristic Fe mineral structures, so-called twisted stalks or tubular sheaths. 28159791 1 61 theme elevated 226:233 arg1 Fe 235:236 elevated Fe 226:236 elevated Fe(II) 226:240 Microaerophilic Fe(II) oxidizers are commonly found in habitats containing elevated Fe(II) and low O2 concentrations and often produce characteristic Fe mineral structures, so-called twisted stalks or tubular sheaths. 28159791 8 62 theme Fe 1944:1945 arg1 cycle.IMPORTANCE 1947:1962 the global biogeochemical Fe cycle.IMPORTANCE 1918:1962 the global biogeochemical Fe cycle.IMPORTANCE 1918:1962 Our findings show that obligate microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria group are not restricted to Fe-rich environments but can also be found in low-Fe marine environments, which increases their overall importance for the global biogeochemical Fe cycle.IMPORTANCE So far, only a few isolates of benthic marine microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria exist, and most isolates were obtained from habitats containing elevated Fe concentrations. 28159791 3 63 theme Fe 925:926 arg1 concentrations 928:941 only low Fe concentrations 916:941 only low Fe concentrations (2 to 11 mg of total Fe/g of sediment [dry weight]; 70 to 100 μM dissolved Fe2+ in the porewater) 916:1039 Here, we present two new isolates of marine microaerophilic Fe(II)-oxidizing Zetaproteobacteria that originate from typical coastal marine sediments containing only low Fe concentrations (2 to 11 mg of total Fe/g of sediment [dry weight]; 70 to 100 μM dissolved Fe2+ in the porewater). 28159791 8 64 theme Fe 2026:2027 arg1 oxidizers 2033:2041 benthic marine microaerophilic Fe(II) oxidizers 1995:2041 benthic marine microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria 1995:2077 Our findings show that obligate microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria group are not restricted to Fe-rich environments but can also be found in low-Fe marine environments, which increases their overall importance for the global biogeochemical Fe cycle.IMPORTANCE So far, only a few isolates of benthic marine microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria exist, and most isolates were obtained from habitats containing elevated Fe concentrations. 28159791 8 65 theme marine 1852:1857 arg1 environments 1859:1870 low-Fe marine environments 1845:1870 low-Fe marine environments 1845:1870 Our findings show that obligate microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria group are not restricted to Fe-rich environments but can also be found in low-Fe marine environments, which increases their overall importance for the global biogeochemical Fe cycle.IMPORTANCE So far, only a few isolates of benthic marine microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria exist, and most isolates were obtained from habitats containing elevated Fe concentrations. 28159791 2 66 theme microaerophilic 584:598 arg1 II 603:604 II 603:604 II 603:604 Isolates originating from freshwater habitats are all members of the Betaproteobacteria, while isolates from marine habitats belong almost exclusively to the Zetaproteobacteria So far, only a few isolates of marine microaerophilic Fe(II) oxidizers have been described, all of which are obligate microaerophilic Fe(II) oxidizers and have been thought to be restricted to Fe-rich systems. 28159791 2 66 theme microaerophilic 584:598 arg1 Fe 600:601 microaerophilic Fe 584:601 marine microaerophilic Fe(II) oxidizers 577:615 Isolates originating from freshwater habitats are all members of the Betaproteobacteria, while isolates from marine habitats belong almost exclusively to the Zetaproteobacteria So far, only a few isolates of marine microaerophilic Fe(II) oxidizers have been described, all of which are obligate microaerophilic Fe(II) oxidizers and have been thought to be restricted to Fe-rich systems. 28159791 7 67 theme trace 1656:1660 arg1 metals 1662:1667 trace metals 1656:1667 trace metals 1656:1667 Immobilization experiments with Ni2+ showed that the stalks can function as a sink for trace metals. 28159791 5 68 theme low 1345:1347 arg1 content 1364:1370 a low organic carbon content 1343:1370 a low organic carbon content 1343:1370 We found a low organic carbon content in the stalks (∼0.3 wt%), with mostly polysaccharides and saturated aliphatic chains (most likely lipids). 28159791 2 69 dep Zetaproteobacteria 527:544 arg1 described 627:635 described 627:635 described 627:635 Isolates originating from freshwater habitats are all members of the Betaproteobacteria, while isolates from marine habitats belong almost exclusively to the Zetaproteobacteria So far, only a few isolates of marine microaerophilic Fe(II) oxidizers have been described, all of which are obligate microaerophilic Fe(II) oxidizers and have been thought to be restricted to Fe-rich systems. 28159791 8 70 theme oxidizers 2033:2041 arg1 isolates 1983:1990 only a few isolates 1972:1990 only a few isolates of benthic marine microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria 1972:2077 Our findings show that obligate microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria group are not restricted to Fe-rich environments but can also be found in low-Fe marine environments, which increases their overall importance for the global biogeochemical Fe cycle.IMPORTANCE So far, only a few isolates of benthic marine microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria exist, and most isolates were obtained from habitats containing elevated Fe concentrations. 28159791 4 71 theme microaerophilic 1228:1242 arg1 oxidizers 1251:1259 obligate microaerophilic Fe(II) oxidizers 1219:1259 obligate microaerophilic Fe(II) oxidizers 1219:1259 The two novel Zetaproteobacteria share characteristic physiological properties of the Zetaproteobacteria group, even though they come from low-Fe environments: the isolates are obligate microaerophilic Fe(II) oxidizers and, like most isolated Zetaproteobacteria, they produce twisted stalks. 28159791 4 71 theme microaerophilic 1228:1242 arg1 isolates 1206:1213 the isolates 1202:1213 the isolates 1202:1213 The two novel Zetaproteobacteria share characteristic physiological properties of the Zetaproteobacteria group, even though they come from low-Fe environments: the isolates are obligate microaerophilic Fe(II) oxidizers and, like most isolated Zetaproteobacteria, they produce twisted stalks. 28159791 5 72 theme carbon 1357:1362 arg1 content 1364:1370 a low organic carbon content 1343:1370 a low organic carbon content 1343:1370 We found a low organic carbon content in the stalks (∼0.3 wt%), with mostly polysaccharides and saturated aliphatic chains (most likely lipids). 28159791 9 73 theme Fe 2269:2270 arg1 concentrations 2272:2285 high Fe concentrations 2264:2285 high Fe concentrations 2264:2285 Consequently, it was thought that these microorganisms are important mainly in habitats with high Fe concentrations. 28159791 8 74 theme biogeochemical 1929:1942 arg1 cycle.IMPORTANCE 1947:1962 the global biogeochemical Fe cycle.IMPORTANCE 1918:1962 the global biogeochemical Fe cycle.IMPORTANCE 1918:1962 Our findings show that obligate microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria group are not restricted to Fe-rich environments but can also be found in low-Fe marine environments, which increases their overall importance for the global biogeochemical Fe cycle.IMPORTANCE So far, only a few isolates of benthic marine microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria exist, and most isolates were obtained from habitats containing elevated Fe concentrations. 28159791 12 75 theme organo-mineral 2622:2635 arg1 structures 2637:2646 the typical organo-mineral structures 2610:2646 the typical organo-mineral structures (twisted stalks) that are produced by the isolates 2610:2697 Furthermore, we show that the physiology and the typical organo-mineral structures (twisted stalks) that are produced by the isolates do not notably differ from the physiology and the cell-mineral structures of isolates from environments with high Fe concentrations. 28159791 12 75 theme organo-mineral 2622:2635 arg1 stalks 2657:2662 twisted stalks 2649:2662 twisted stalks 2649:2662 Furthermore, we show that the physiology and the typical organo-mineral structures (twisted stalks) that are produced by the isolates do not notably differ from the physiology and the cell-mineral structures of isolates from environments with high Fe concentrations. 28159791 8 76 contain containing 2132:2141 arg1 habitats 2123:2130 habitats 2123:2130 habitats containing elevated Fe concentrations 2123:2168 Our findings show that obligate microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria group are not restricted to Fe-rich environments but can also be found in low-Fe marine environments, which increases their overall importance for the global biogeochemical Fe cycle.IMPORTANCE So far, only a few isolates of benthic marine microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria exist, and most isolates were obtained from habitats containing elevated Fe concentrations. 28159791 8 76 contain containing 2132:2141 arg2 concentrations 2155:2168 elevated Fe concentrations 2143:2168 elevated Fe concentrations 2143:2168 Our findings show that obligate microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria group are not restricted to Fe-rich environments but can also be found in low-Fe marine environments, which increases their overall importance for the global biogeochemical Fe cycle.IMPORTANCE So far, only a few isolates of benthic marine microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria exist, and most isolates were obtained from habitats containing elevated Fe concentrations. 28159791 8 77 theme low-Fe 1845:1850 arg1 environments 1859:1870 low-Fe marine environments 1845:1870 low-Fe marine environments 1845:1870 Our findings show that obligate microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria group are not restricted to Fe-rich environments but can also be found in low-Fe marine environments, which increases their overall importance for the global biogeochemical Fe cycle.IMPORTANCE So far, only a few isolates of benthic marine microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria exist, and most isolates were obtained from habitats containing elevated Fe concentrations. 28159791 3 78 theme total 958:962 arg1 Fe/g 964:967 total Fe/g 958:967 total Fe/g of sediment [dry weight 958:991 Here, we present two new isolates of marine microaerophilic Fe(II)-oxidizing Zetaproteobacteria that originate from typical coastal marine sediments containing only low Fe concentrations (2 to 11 mg of total Fe/g of sediment [dry weight]; 70 to 100 μM dissolved Fe2+ in the porewater). 28159791 2 79 theme Fe-rich 739:745 arg1 systems 747:753 Fe-rich systems 739:753 Fe-rich systems 739:753 Isolates originating from freshwater habitats are all members of the Betaproteobacteria, while isolates from marine habitats belong almost exclusively to the Zetaproteobacteria So far, only a few isolates of marine microaerophilic Fe(II) oxidizers have been described, all of which are obligate microaerophilic Fe(II) oxidizers and have been thought to be restricted to Fe-rich systems. 28159791 10 80 theme present 2359:2365 arg1 study 2367:2371 the present study 2355:2371 the present study 2355:2371 The two novel isolates of Zetaproteobacteria that are presented in the present study were isolated from typical coastal marine sediments that do not contain elevated Fe concentrations. 28159791 3 81 dep concentrations 928:941 arg1 mg 952:953 2 to 11 mg 944:953 2 to 11 mg of total Fe/g of sediment [dry weight 944:991 Here, we present two new isolates of marine microaerophilic Fe(II)-oxidizing Zetaproteobacteria that originate from typical coastal marine sediments containing only low Fe concentrations (2 to 11 mg of total Fe/g of sediment [dry weight]; 70 to 100 μM dissolved Fe2+ in the porewater). 28159791 3 81 dep concentrations 928:941 arg1 μM 1005:1006 70 to 100 μM 995:1006 only low Fe concentrations (2 to 11 mg of total Fe/g of sediment [dry weight]; 70 to 100 μM dissolved Fe2+ in the porewater) 916:1039 Here, we present two new isolates of marine microaerophilic Fe(II)-oxidizing Zetaproteobacteria that originate from typical coastal marine sediments containing only low Fe concentrations (2 to 11 mg of total Fe/g of sediment [dry weight]; 70 to 100 μM dissolved Fe2+ in the porewater). 28159791 6 82 from minerals 1486:1493 arg1 stalks 1502:1507 the stalks 1498:1507 the stalks 1498:1507 The Fe minerals in the stalks were identified as lepidocrocite and possibly ferrihydrite. 28159791 10 83 theme coastal 2400:2406 arg1 sediments 2415:2423 typical coastal marine sediments 2392:2423 typical coastal marine sediments that do not contain elevated Fe concentrations 2392:2470 The two novel isolates of Zetaproteobacteria that are presented in the present study were isolated from typical coastal marine sediments that do not contain elevated Fe concentrations. 28159791 0 84 theme Twisted 135:141 arg1 Stalks 143:148 Their Twisted Stalks 129:148 Their Twisted Stalks 129:148 Microaerophilic Fe(II)-Oxidizing Zetaproteobacteria Isolated from Low-Fe Marine Coastal Sediments: Physiology and Composition of Their Twisted Stalks. 28159791 8 85 theme most 2090:2093 arg1 isolates 2095:2102 most isolates 2090:2102 most isolates 2090:2102 Our findings show that obligate microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria group are not restricted to Fe-rich environments but can also be found in low-Fe marine environments, which increases their overall importance for the global biogeochemical Fe cycle.IMPORTANCE So far, only a few isolates of benthic marine microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria exist, and most isolates were obtained from habitats containing elevated Fe concentrations. 28159791 4 86 theme physiological 1096:1108 arg1 properties 1110:1119 characteristic physiological properties 1081:1119 characteristic physiological properties of the Zetaproteobacteria group 1081:1151 The two novel Zetaproteobacteria share characteristic physiological properties of the Zetaproteobacteria group, even though they come from low-Fe environments: the isolates are obligate microaerophilic Fe(II) oxidizers and, like most isolated Zetaproteobacteria, they produce twisted stalks. 28159791 10 87 theme novel 2296:2300 arg1 isolates 2302:2309 The two novel isolates 2288:2309 The two novel isolates of Zetaproteobacteria that are presented in the present study 2288:2371 The two novel isolates of Zetaproteobacteria that are presented in the present study were isolated from typical coastal marine sediments that do not contain elevated Fe concentrations. 28159791 1 88 contain containing 215:224 arg1 habitats 206:213 habitats 206:213 habitats containing elevated Fe(II) and low O2 concentrations 206:266 Microaerophilic Fe(II) oxidizers are commonly found in habitats containing elevated Fe(II) and low O2 concentrations and often produce characteristic Fe mineral structures, so-called twisted stalks or tubular sheaths. 28159791 1 88 contain containing 215:224 arg2 Fe 235:236 elevated Fe 226:236 elevated Fe(II) 226:240 Microaerophilic Fe(II) oxidizers are commonly found in habitats containing elevated Fe(II) and low O2 concentrations and often produce characteristic Fe mineral structures, so-called twisted stalks or tubular sheaths. 28159791 1 88 contain containing 215:224 arg2 II 238:239 II 238:239 II 238:239 Microaerophilic Fe(II) oxidizers are commonly found in habitats containing elevated Fe(II) and low O2 concentrations and often produce characteristic Fe mineral structures, so-called twisted stalks or tubular sheaths. 28159791 1 88 contain containing 215:224 arg2 concentrations 253:266 low O2 concentrations 246:266 low O2 concentrations 246:266 Microaerophilic Fe(II) oxidizers are commonly found in habitats containing elevated Fe(II) and low O2 concentrations and often produce characteristic Fe mineral structures, so-called twisted stalks or tubular sheaths. 28159791 2 89 theme microaerophilic 664:678 arg1 Fe 680:681 microaerophilic Fe 664:681 obligate microaerophilic Fe(II) oxidizers 655:695 Isolates originating from freshwater habitats are all members of the Betaproteobacteria, while isolates from marine habitats belong almost exclusively to the Zetaproteobacteria So far, only a few isolates of marine microaerophilic Fe(II) oxidizers have been described, all of which are obligate microaerophilic Fe(II) oxidizers and have been thought to be restricted to Fe-rich systems. 28159791 2 89 theme microaerophilic 664:678 arg1 II 683:684 II 683:684 II 683:684 Isolates originating from freshwater habitats are all members of the Betaproteobacteria, while isolates from marine habitats belong almost exclusively to the Zetaproteobacteria So far, only a few isolates of marine microaerophilic Fe(II) oxidizers have been described, all of which are obligate microaerophilic Fe(II) oxidizers and have been thought to be restricted to Fe-rich systems. 28159791 4 90 theme isolated 1276:1283 arg1 Zetaproteobacteria 1285:1302 most isolated Zetaproteobacteria 1271:1302 most isolated Zetaproteobacteria 1271:1302 The two novel Zetaproteobacteria share characteristic physiological properties of the Zetaproteobacteria group, even though they come from low-Fe environments: the isolates are obligate microaerophilic Fe(II) oxidizers and, like most isolated Zetaproteobacteria, they produce twisted stalks. 28159791 3 91 theme microaerophilic 800:814 arg1 Zetaproteobacteria 833:850 marine microaerophilic Fe(II)-oxidizing Zetaproteobacteria 793:850 marine microaerophilic Fe(II)-oxidizing Zetaproteobacteria 793:850 Here, we present two new isolates of marine microaerophilic Fe(II)-oxidizing Zetaproteobacteria that originate from typical coastal marine sediments containing only low Fe concentrations (2 to 11 mg of total Fe/g of sediment [dry weight]; 70 to 100 μM dissolved Fe2+ in the porewater). 28159791 7 92 with experiments 1584:1594 arg1 Ni2+ 1601:1604 Ni2+ 1601:1604 Ni2+ 1601:1604 Immobilization experiments with Ni2+ showed that the stalks can function as a sink for trace metals. 28159791 4 93 theme novel 1050:1054 arg1 Zetaproteobacteria 1056:1073 The two novel Zetaproteobacteria 1042:1073 The two novel Zetaproteobacteria 1042:1073 The two novel Zetaproteobacteria share characteristic physiological properties of the Zetaproteobacteria group, even though they come from low-Fe environments: the isolates are obligate microaerophilic Fe(II) oxidizers and, like most isolated Zetaproteobacteria, they produce twisted stalks. 28159791 0 94 theme Low-Fe 66:71 arg1 Composition 114:124 Composition 114:124 Composition 114:124 Microaerophilic Fe(II)-Oxidizing Zetaproteobacteria Isolated from Low-Fe Marine Coastal Sediments: Physiology and Composition of Their Twisted Stalks. 28159791 0 94 theme Low-Fe 66:71 arg1 Physiology 99:108 Physiology 99:108 Physiology 99:108 Microaerophilic Fe(II)-Oxidizing Zetaproteobacteria Isolated from Low-Fe Marine Coastal Sediments: Physiology and Composition of Their Twisted Stalks. 28159791 0 94 theme Low-Fe 66:71 arg1 Sediments 88:96 Low-Fe Marine Coastal Sediments 66:96 Low-Fe Marine Coastal Sediments: Physiology and Composition of Their Twisted Stalks 66:148 Microaerophilic Fe(II)-Oxidizing Zetaproteobacteria Isolated from Low-Fe Marine Coastal Sediments: Physiology and Composition of Their Twisted Stalks. 28159791 1 95 located found 197:201 arg1 habitats 206:213 habitats 206:213 habitats containing elevated Fe(II) and low O2 concentrations 206:266 Microaerophilic Fe(II) oxidizers are commonly found in habitats containing elevated Fe(II) and low O2 concentrations and often produce characteristic Fe mineral structures, so-called twisted stalks or tubular sheaths. 28159791 1 95 located found 197:201 arg2 oxidizers 174:182 Microaerophilic Fe(II) oxidizers 151:182 Microaerophilic Fe(II) oxidizers 151:182 Microaerophilic Fe(II) oxidizers are commonly found in habitats containing elevated Fe(II) and low O2 concentrations and often produce characteristic Fe mineral structures, so-called twisted stalks or tubular sheaths. 28159791 10 96 theme Fe 2454:2455 arg1 concentrations 2457:2470 elevated Fe concentrations 2445:2470 elevated Fe concentrations 2445:2470 The two novel isolates of Zetaproteobacteria that are presented in the present study were isolated from typical coastal marine sediments that do not contain elevated Fe concentrations. 28159791 0 97 theme Coastal 80:86 arg1 Composition 114:124 Composition 114:124 Composition 114:124 Microaerophilic Fe(II)-Oxidizing Zetaproteobacteria Isolated from Low-Fe Marine Coastal Sediments: Physiology and Composition of Their Twisted Stalks. 28159791 0 97 theme Coastal 80:86 arg1 Physiology 99:108 Physiology 99:108 Physiology 99:108 Microaerophilic Fe(II)-Oxidizing Zetaproteobacteria Isolated from Low-Fe Marine Coastal Sediments: Physiology and Composition of Their Twisted Stalks. 28159791 0 97 theme Coastal 80:86 arg1 Sediments 88:96 Low-Fe Marine Coastal Sediments 66:96 Low-Fe Marine Coastal Sediments: Physiology and Composition of Their Twisted Stalks 66:148 Microaerophilic Fe(II)-Oxidizing Zetaproteobacteria Isolated from Low-Fe Marine Coastal Sediments: Physiology and Composition of Their Twisted Stalks. 28159791 12 98 from structures 2762:2771 arg1 environments 2790:2801 environments 2790:2801 environments with high Fe concentrations 2790:2829 Furthermore, we show that the physiology and the typical organo-mineral structures (twisted stalks) that are produced by the isolates do not notably differ from the physiology and the cell-mineral structures of isolates from environments with high Fe concentrations. 28159791 1 99 theme Microaerophilic 151:165 arg1 oxidizers 174:182 Microaerophilic Fe(II) oxidizers 151:182 Microaerophilic Fe(II) oxidizers 151:182 Microaerophilic Fe(II) oxidizers are commonly found in habitats containing elevated Fe(II) and low O2 concentrations and often produce characteristic Fe mineral structures, so-called twisted stalks or tubular sheaths. 28159791 3 100 theme new 777:779 arg1 isolates 781:788 two new isolates 773:788 two new isolates of marine microaerophilic Fe(II)-oxidizing Zetaproteobacteria that originate from typical coastal marine sediments containing only low Fe concentrations (2 to 11 mg of total Fe/g of sediment [dry weight]; 70 to 100 μM dissolved Fe2+ in the porewater) 773:1039 Here, we present two new isolates of marine microaerophilic Fe(II)-oxidizing Zetaproteobacteria that originate from typical coastal marine sediments containing only low Fe concentrations (2 to 11 mg of total Fe/g of sediment [dry weight]; 70 to 100 μM dissolved Fe2+ in the porewater). 28159791 1 101 theme so-called 324:332 arg1 stalks 342:347 so-called twisted stalks 324:347 so-called twisted stalks 324:347 Microaerophilic Fe(II) oxidizers are commonly found in habitats containing elevated Fe(II) and low O2 concentrations and often produce characteristic Fe mineral structures, so-called twisted stalks or tubular sheaths. 28159791 3 102 theme [dry 981:984 arg1 weight 986:991 sediment [dry weight 972:991 sediment [dry weight 972:991 Here, we present two new isolates of marine microaerophilic Fe(II)-oxidizing Zetaproteobacteria that originate from typical coastal marine sediments containing only low Fe concentrations (2 to 11 mg of total Fe/g of sediment [dry weight]; 70 to 100 μM dissolved Fe2+ in the porewater). 28159791 9 103 from habitats 2250:2257 arg1 important 2230:2238 important 2230:2238 important 2230:2238 Consequently, it was thought that these microorganisms are important mainly in habitats with high Fe concentrations. 28159791 12 104 from physiology 2730:2739 arg1 environments 2790:2801 environments 2790:2801 environments with high Fe concentrations 2790:2829 Furthermore, we show that the physiology and the typical organo-mineral structures (twisted stalks) that are produced by the isolates do not notably differ from the physiology and the cell-mineral structures of isolates from environments with high Fe concentrations. 28159791 8 105 theme obligate 1693:1700 arg1 oxidizers 1725:1733 obligate microaerophilic Fe(II) oxidizers 1693:1733 obligate microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria group 1693:1775 Our findings show that obligate microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria group are not restricted to Fe-rich environments but can also be found in low-Fe marine environments, which increases their overall importance for the global biogeochemical Fe cycle.IMPORTANCE So far, only a few isolates of benthic marine microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria exist, and most isolates were obtained from habitats containing elevated Fe concentrations. 28159791 4 106 theme Zetaproteobacteria 1128:1145 arg1 group 1147:1151 the Zetaproteobacteria group 1124:1151 the Zetaproteobacteria group 1124:1151 The two novel Zetaproteobacteria share characteristic physiological properties of the Zetaproteobacteria group, even though they come from low-Fe environments: the isolates are obligate microaerophilic Fe(II) oxidizers and, like most isolated Zetaproteobacteria, they produce twisted stalks. 28159791 0 107 theme Fe 16:17 arg1 Zetaproteobacteria 33:50 Microaerophilic Fe(II)-Oxidizing Zetaproteobacteria 0:50 Microaerophilic Fe(II)-Oxidizing Zetaproteobacteria 0:50 Microaerophilic Fe(II)-Oxidizing Zetaproteobacteria Isolated from Low-Fe Marine Coastal Sediments: Physiology and Composition of Their Twisted Stalks. 28159791 1 108 theme tubular 352:358 arg1 sheaths 360:366 tubular sheaths 352:366 tubular sheaths 352:366 Microaerophilic Fe(II) oxidizers are commonly found in habitats containing elevated Fe(II) and low O2 concentrations and often produce characteristic Fe mineral structures, so-called twisted stalks or tubular sheaths. 28159791 8 109 theme Fe 1718:1719 arg1 oxidizers 1725:1733 obligate microaerophilic Fe(II) oxidizers 1693:1733 obligate microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria group 1693:1775 Our findings show that obligate microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria group are not restricted to Fe-rich environments but can also be found in low-Fe marine environments, which increases their overall importance for the global biogeochemical Fe cycle.IMPORTANCE So far, only a few isolates of benthic marine microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria exist, and most isolates were obtained from habitats containing elevated Fe concentrations. 28159791 7 110 theme Immobilization 1569:1582 arg1 experiments 1584:1594 Immobilization experiments 1569:1594 Immobilization experiments with Ni2+ 1569:1604 Immobilization experiments with Ni2+ showed that the stalks can function as a sink for trace metals. 28159791 10 111 theme Zetaproteobacteria 2314:2331 arg1 isolates 2302:2309 The two novel isolates 2288:2309 The two novel isolates of Zetaproteobacteria that are presented in the present study 2288:2371 The two novel isolates of Zetaproteobacteria that are presented in the present study were isolated from typical coastal marine sediments that do not contain elevated Fe concentrations. 28159791 6 112 theme Fe 1483:1484 arg1 lepidocrocite 1528:1540 lepidocrocite 1528:1540 lepidocrocite 1528:1540 The Fe minerals in the stalks were identified as lepidocrocite and possibly ferrihydrite. 28159791 6 112 theme Fe 1483:1484 arg1 ferrihydrite 1555:1566 ferrihydrite 1555:1566 ferrihydrite 1555:1566 The Fe minerals in the stalks were identified as lepidocrocite and possibly ferrihydrite. 28159791 6 112 theme Fe 1483:1484 arg1 minerals 1486:1493 The Fe minerals 1479:1493 The Fe minerals in the stalks 1479:1507 The Fe minerals in the stalks were identified as lepidocrocite and possibly ferrihydrite. 28159791 3 113 theme marine 888:893 arg1 sediments 895:903 typical coastal marine sediments 872:903 typical coastal marine sediments containing only low Fe concentrations (2 to 11 mg of total Fe/g of sediment [dry weight]; 70 to 100 μM dissolved Fe2+ in the porewater) 872:1039 Here, we present two new isolates of marine microaerophilic Fe(II)-oxidizing Zetaproteobacteria that originate from typical coastal marine sediments containing only low Fe concentrations (2 to 11 mg of total Fe/g of sediment [dry weight]; 70 to 100 μM dissolved Fe2+ in the porewater). 28159791 0 114 theme -Oxidizing 22:31 arg1 Zetaproteobacteria 33:50 Microaerophilic Fe(II)-Oxidizing Zetaproteobacteria 0:50 Microaerophilic Fe(II)-Oxidizing Zetaproteobacteria 0:50 Microaerophilic Fe(II)-Oxidizing Zetaproteobacteria Isolated from Low-Fe Marine Coastal Sediments: Physiology and Composition of Their Twisted Stalks. 28159791 3 115 theme dissolved 1008:1016 arg1 Fe2+ 1018:1021 dissolved Fe2+ 1008:1021 only low Fe concentrations (2 to 11 mg of total Fe/g of sediment [dry weight]; 70 to 100 μM dissolved Fe2+ in the porewater) 916:1039 Here, we present two new isolates of marine microaerophilic Fe(II)-oxidizing Zetaproteobacteria that originate from typical coastal marine sediments containing only low Fe concentrations (2 to 11 mg of total Fe/g of sediment [dry weight]; 70 to 100 μM dissolved Fe2+ in the porewater). 28159791 8 116 theme Fe 2152:2153 arg1 concentrations 2155:2168 elevated Fe concentrations 2143:2168 elevated Fe concentrations 2143:2168 Our findings show that obligate microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria group are not restricted to Fe-rich environments but can also be found in low-Fe marine environments, which increases their overall importance for the global biogeochemical Fe cycle.IMPORTANCE So far, only a few isolates of benthic marine microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria exist, and most isolates were obtained from habitats containing elevated Fe concentrations. 28159791 3 117 theme typical 872:878 arg1 sediments 895:903 typical coastal marine sediments 872:903 typical coastal marine sediments containing only low Fe concentrations (2 to 11 mg of total Fe/g of sediment [dry weight]; 70 to 100 μM dissolved Fe2+ in the porewater) 872:1039 Here, we present two new isolates of marine microaerophilic Fe(II)-oxidizing Zetaproteobacteria that originate from typical coastal marine sediments containing only low Fe concentrations (2 to 11 mg of total Fe/g of sediment [dry weight]; 70 to 100 μM dissolved Fe2+ in the porewater). 28159791 5 118 theme aliphatic 1440:1448 arg1 chains 1450:1455 saturated aliphatic chains 1430:1455 saturated aliphatic chains 1430:1455 We found a low organic carbon content in the stalks (∼0.3 wt%), with mostly polysaccharides and saturated aliphatic chains (most likely lipids). 28159791 4 119 theme obligate 1219:1226 arg1 oxidizers 1251:1259 obligate microaerophilic Fe(II) oxidizers 1219:1259 obligate microaerophilic Fe(II) oxidizers 1219:1259 The two novel Zetaproteobacteria share characteristic physiological properties of the Zetaproteobacteria group, even though they come from low-Fe environments: the isolates are obligate microaerophilic Fe(II) oxidizers and, like most isolated Zetaproteobacteria, they produce twisted stalks. 28159791 4 119 theme obligate 1219:1226 arg1 isolates 1206:1213 the isolates 1202:1213 the isolates 1202:1213 The two novel Zetaproteobacteria share characteristic physiological properties of the Zetaproteobacteria group, even though they come from low-Fe environments: the isolates are obligate microaerophilic Fe(II) oxidizers and, like most isolated Zetaproteobacteria, they produce twisted stalks. 28159791 3 120 dep 100 1001:1003 arg1 to 998:999 to 998:999 to 998:999 Here, we present two new isolates of marine microaerophilic Fe(II)-oxidizing Zetaproteobacteria that originate from typical coastal marine sediments containing only low Fe concentrations (2 to 11 mg of total Fe/g of sediment [dry weight]; 70 to 100 μM dissolved Fe2+ in the porewater). 28159791 10 121 contain contain 2437:2443 arg2 concentrations 2457:2470 elevated Fe concentrations 2445:2470 elevated Fe concentrations 2445:2470 The two novel isolates of Zetaproteobacteria that are presented in the present study were isolated from typical coastal marine sediments that do not contain elevated Fe concentrations. 28159791 10 121 contain contain 2437:2443 arg1 sediments 2415:2423 typical coastal marine sediments 2392:2423 typical coastal marine sediments that do not contain elevated Fe concentrations 2392:2470 The two novel isolates of Zetaproteobacteria that are presented in the present study were isolated from typical coastal marine sediments that do not contain elevated Fe concentrations. 28159791 3 122 theme low 921:923 arg1 concentrations 928:941 only low Fe concentrations 916:941 only low Fe concentrations (2 to 11 mg of total Fe/g of sediment [dry weight]; 70 to 100 μM dissolved Fe2+ in the porewater) 916:1039 Here, we present two new isolates of marine microaerophilic Fe(II)-oxidizing Zetaproteobacteria that originate from typical coastal marine sediments containing only low Fe concentrations (2 to 11 mg of total Fe/g of sediment [dry weight]; 70 to 100 μM dissolved Fe2+ in the porewater). 28159791 8 123 theme benthic 1995:2001 arg1 II 2029:2030 II 2029:2030 II 2029:2030 Our findings show that obligate microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria group are not restricted to Fe-rich environments but can also be found in low-Fe marine environments, which increases their overall importance for the global biogeochemical Fe cycle.IMPORTANCE So far, only a few isolates of benthic marine microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria exist, and most isolates were obtained from habitats containing elevated Fe concentrations. 28159791 8 123 theme benthic 1995:2001 arg1 Fe 2026:2027 benthic marine microaerophilic Fe 1995:2027 benthic marine microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria 1995:2077 Our findings show that obligate microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria group are not restricted to Fe-rich environments but can also be found in low-Fe marine environments, which increases their overall importance for the global biogeochemical Fe cycle.IMPORTANCE So far, only a few isolates of benthic marine microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria exist, and most isolates were obtained from habitats containing elevated Fe concentrations. 28159791 2 124 theme Betaproteobacteria 438:455 arg1 Isolates 369:376 Isolates 369:376 Isolates originating from freshwater habitats 369:413 Isolates originating from freshwater habitats are all members of the Betaproteobacteria, while isolates from marine habitats belong almost exclusively to the Zetaproteobacteria So far, only a few isolates of marine microaerophilic Fe(II) oxidizers have been described, all of which are obligate microaerophilic Fe(II) oxidizers and have been thought to be restricted to Fe-rich systems. 28159791 2 124 theme Betaproteobacteria 438:455 arg1 members 423:429 all members 419:429 all members of the Betaproteobacteria 419:455 Isolates originating from freshwater habitats are all members of the Betaproteobacteria, while isolates from marine habitats belong almost exclusively to the Zetaproteobacteria So far, only a few isolates of marine microaerophilic Fe(II) oxidizers have been described, all of which are obligate microaerophilic Fe(II) oxidizers and have been thought to be restricted to Fe-rich systems. 28159791 4 125 theme low-Fe 1181:1186 arg1 environments 1188:1199 low-Fe environments 1181:1199 low-Fe environments 1181:1199 The two novel Zetaproteobacteria share characteristic physiological properties of the Zetaproteobacteria group, even though they come from low-Fe environments: the isolates are obligate microaerophilic Fe(II) oxidizers and, like most isolated Zetaproteobacteria, they produce twisted stalks. 28159791 12 126 theme high 2808:2811 arg1 concentrations 2816:2829 high Fe concentrations 2808:2829 high Fe concentrations 2808:2829 Furthermore, we show that the physiology and the typical organo-mineral structures (twisted stalks) that are produced by the isolates do not notably differ from the physiology and the cell-mineral structures of isolates from environments with high Fe concentrations. 28159791 1 127 theme Fe 301:302 arg1 structures 312:321 Fe mineral structures 301:321 Fe mineral structures 301:321 Microaerophilic Fe(II) oxidizers are commonly found in habitats containing elevated Fe(II) and low O2 concentrations and often produce characteristic Fe mineral structures, so-called twisted stalks or tubular sheaths. 28159791 8 128 theme microaerophilic 2010:2024 arg1 II 2029:2030 II 2029:2030 II 2029:2030 Our findings show that obligate microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria group are not restricted to Fe-rich environments but can also be found in low-Fe marine environments, which increases their overall importance for the global biogeochemical Fe cycle.IMPORTANCE So far, only a few isolates of benthic marine microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria exist, and most isolates were obtained from habitats containing elevated Fe concentrations. 28159791 8 128 theme microaerophilic 2010:2024 arg1 Fe 2026:2027 benthic marine microaerophilic Fe 1995:2027 benthic marine microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria 1995:2077 Our findings show that obligate microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria group are not restricted to Fe-rich environments but can also be found in low-Fe marine environments, which increases their overall importance for the global biogeochemical Fe cycle.IMPORTANCE So far, only a few isolates of benthic marine microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria exist, and most isolates were obtained from habitats containing elevated Fe concentrations. 28159791 12 129 theme isolates 2776:2783 arg1 physiology 2730:2739 physiology 2730:2739 physiology 2730:2739 Furthermore, we show that the physiology and the typical organo-mineral structures (twisted stalks) that are produced by the isolates do not notably differ from the physiology and the cell-mineral structures of isolates from environments with high Fe concentrations. 28159791 12 129 theme isolates 2776:2783 arg1 structures 2762:2771 the cell-mineral structures 2745:2771 the cell-mineral structures 2745:2771 Furthermore, we show that the physiology and the typical organo-mineral structures (twisted stalks) that are produced by the isolates do not notably differ from the physiology and the cell-mineral structures of isolates from environments with high Fe concentrations. 28159791 8 130 theme overall 1895:1901 arg1 importance 1903:1912 their overall importance 1889:1912 their overall importance for the global biogeochemical Fe cycle.IMPORTANCE 1889:1962 Our findings show that obligate microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria group are not restricted to Fe-rich environments but can also be found in low-Fe marine environments, which increases their overall importance for the global biogeochemical Fe cycle.IMPORTANCE So far, only a few isolates of benthic marine microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria exist, and most isolates were obtained from habitats containing elevated Fe concentrations. 27648759 8 0 theme biofilms 1169:1176 arg1 Structure 1143:1151 Structure 1143:1151 Structure of dual-species biofilms 1143:1176 Structure of dual-species biofilms was more compact and their surface was >8 times smoother than mono-species C. jejuni biofilm, as indicated by atomic force microscopy. 27648759 10 1 theme polar 1704:1708 arg1 liquids 1710:1716 polar liquids 1704:1716 polar liquids 1704:1716 The surface of all biofilms was hydrophilic, but total surface energy of dual-species biofilms (ranging from 52.5 to 56.2mJ/m2) was lower than that of mono-species C. jejuni biofilm, leading to more resistance to wetting by polar liquids. 27648759 9 2 theme longer 1431:1436 arg1 time 1438:1441 a longer time 1429:1441 a longer time than mono-species C. jejuni biofilm 1429:1477 Under desiccation stress, water content of dual-species biofilms decreased slowly and remained at higher levels for a longer time than mono-species C. jejuni biofilm. 27648759 6 3 theme morphological 875:887 arg1 features 889:896 chemical, physical and morphological features 852:896 chemical, physical and morphological features of biofilms 852:908 To elucidate the mechanism of protection mode, chemical, physical and morphological features of biofilms were characterized. 27648759 7 4 theme jejuni 1127:1132 arg1 biofilm 1134:1140 mono-species C. jejuni biofilm 1111:1140 mono-species C. jejuni biofilm 1111:1140 Dual-species biofilms contained a higher level of extracellular polymeric substances with a more diversified chemical composition, especially for polysaccharides and proteins, than mono-species C. jejuni biofilm. 27648759 6 5 theme physical 862:869 arg1 features 889:896 chemical, physical and morphological features 852:896 chemical, physical and morphological features of biofilms 852:908 To elucidate the mechanism of protection mode, chemical, physical and morphological features of biofilms were characterized. 27648759 8 6 theme jejuni 1256:1261 arg1 biofilm 1263:1269 mono-species C. jejuni biofilm 1240:1269 mono-species C. jejuni biofilm 1240:1269 Structure of dual-species biofilms was more compact and their surface was >8 times smoother than mono-species C. jejuni biofilm, as indicated by atomic force microscopy. 27648759 7 7 theme mono-species 1111:1122 arg1 jejuni 1127:1132 mono-species C. jejuni 1111:1132 mono-species C. jejuni biofilm 1111:1140 Dual-species biofilms contained a higher level of extracellular polymeric substances with a more diversified chemical composition, especially for polysaccharides and proteins, than mono-species C. jejuni biofilm. 27648759 0 8 theme Chemical 0:7 arg1 properties 37:46 Chemical, physical and morphological properties 0:46 Chemical, physical and morphological properties of bacterial biofilms 0:68 Chemical, physical and morphological properties of bacterial biofilms affect survival of encased Campylobacter jejuni F38011 under aerobic stress. 27648759 9 9 theme C. 1461:1462 arg1 biofilm 1471:1477 mono-species C. jejuni biofilm 1448:1477 mono-species C. jejuni biofilm 1448:1477 Under desiccation stress, water content of dual-species biofilms decreased slowly and remained at higher levels for a longer time than mono-species C. jejuni biofilm. 27648759 6 10 theme chemical 852:859 arg1 features 889:896 chemical, physical and morphological features 852:896 chemical, physical and morphological features of biofilms 852:908 To elucidate the mechanism of protection mode, chemical, physical and morphological features of biofilms were characterized. 27648759 2 11 theme processing 314:323 arg1 facilities 325:334 poultry processing facilities 306:334 poultry processing facilities 306:334 The presence of C. jejuni encased in biofilms found in meat and poultry processing facilities may be the major strategy for its survival and dissemination in aerobic environment. 27648759 1 12 theme leading 202:208 arg1 cause 210:214 leading cause 202:214 leading cause of human gastroenteritis 202:239 Campylobacter jejuni is a microaerophilic pathogen and leading cause of human gastroenteritis. 27648759 8 13 theme smoother 1226:1233 arg1 times 1220:1224 >8 times 1217:1224 >8 times smoother than mono-species C. jejuni biofilm 1217:1269 Structure of dual-species biofilms was more compact and their surface was >8 times smoother than mono-species C. jejuni biofilm, as indicated by atomic force microscopy. 27648759 4 14 theme jejuni 688:693 arg1 biofilm 695:701 mono-species C. jejuni biofilm 672:701 mono-species C. jejuni biofilm 672:701 After 4days' exposure to aerobic stress, no viable C. jejuni cells could be detected from mono-species C. jejuni biofilm. 27648759 4 15 theme C. 633:634 arg1 cells 643:647 no viable C. jejuni cells 623:647 no viable C. jejuni cells 623:647 After 4days' exposure to aerobic stress, no viable C. jejuni cells could be detected from mono-species C. jejuni biofilm. 27648759 11 16 theme C. 1822:1823 arg1 jejuni 1825:1830 C. jejuni 1822:1830 C. jejuni 1822:1830 This knowledge can aid in developing intervention strategies to decrease the survival and dispersal of C. jejuni into foods or environment. 27648759 1 17 theme gastroenteritis 225:239 arg1 jejuni 161:166 Campylobacter jejuni 147:166 Campylobacter jejuni 147:166 Campylobacter jejuni is a microaerophilic pathogen and leading cause of human gastroenteritis. 27648759 1 17 theme gastroenteritis 225:239 arg1 pathogen 189:196 a microaerophilic pathogen 171:196 a microaerophilic pathogen 171:196 Campylobacter jejuni is a microaerophilic pathogen and leading cause of human gastroenteritis. 27648759 1 17 theme gastroenteritis 225:239 arg1 cause 210:214 leading cause 202:214 leading cause of human gastroenteritis 202:239 Campylobacter jejuni is a microaerophilic pathogen and leading cause of human gastroenteritis. 27648759 8 18 theme mono-species 1240:1251 arg1 jejuni 1256:1261 mono-species C. jejuni 1240:1261 mono-species C. jejuni biofilm 1240:1269 Structure of dual-species biofilms was more compact and their surface was >8 times smoother than mono-species C. jejuni biofilm, as indicated by atomic force microscopy. 27648759 7 19 theme substances 1004:1013 arg1 level 971:975 a higher level 962:975 a higher level of extracellular polymeric substances with a more diversified chemical composition, especially for polysaccharides and proteins 962:1103 Dual-species biofilms contained a higher level of extracellular polymeric substances with a more diversified chemical composition, especially for polysaccharides and proteins, than mono-species C. jejuni biofilm. 27648759 7 20 theme chemical 1039:1046 arg1 composition 1048:1058 a more diversified chemical composition 1020:1058 a more diversified chemical composition 1020:1058 Dual-species biofilms contained a higher level of extracellular polymeric substances with a more diversified chemical composition, especially for polysaccharides and proteins, than mono-species C. jejuni biofilm. 27648759 7 21 theme extracellular 980:992 arg1 substances 1004:1013 extracellular polymeric substances 980:1013 extracellular polymeric substances 980:1013 Dual-species biofilms contained a higher level of extracellular polymeric substances with a more diversified chemical composition, especially for polysaccharides and proteins, than mono-species C. jejuni biofilm. 27648759 0 22 theme biofilms 61:68 arg1 properties 37:46 Chemical, physical and morphological properties 0:46 Chemical, physical and morphological properties of bacterial biofilms 0:68 Chemical, physical and morphological properties of bacterial biofilms affect survival of encased Campylobacter jejuni F38011 under aerobic stress. 27648759 2 23 theme C. 258:259 arg1 jejuni 261:266 C. jejuni 258:266 C. jejuni encased in biofilms found in meat and poultry processing facilities 258:334 The presence of C. jejuni encased in biofilms found in meat and poultry processing facilities may be the major strategy for its survival and dissemination in aerobic environment. 27648759 4 24 theme C. 685:686 arg1 jejuni 688:693 mono-species C. jejuni 672:693 mono-species C. jejuni biofilm 672:701 After 4days' exposure to aerobic stress, no viable C. jejuni cells could be detected from mono-species C. jejuni biofilm. 27648759 5 25 theme C. 750:751 arg1 jejuni 753:758 viable C. jejuni 743:758 viable C. jejuni 743:758 In contrast, at least 4.7logCFU/cm2 of viable C. jejuni cells existed in some dual-species biofilms. 27648759 11 26 dep survival 1796:1803 arg1 the 1792:1794 the 1792:1794 the 1792:1794 This knowledge can aid in developing intervention strategies to decrease the survival and dispersal of C. jejuni into foods or environment. 27648759 0 27 theme encased 89:95 arg1 jejuni 111:116 encased Campylobacter jejuni 89:116 encased Campylobacter jejuni F38011 89:123 Chemical, physical and morphological properties of bacterial biofilms affect survival of encased Campylobacter jejuni F38011 under aerobic stress. 27648759 9 28 theme desiccation 1319:1329 arg1 stress 1331:1336 desiccation stress 1319:1336 desiccation stress 1319:1336 Under desiccation stress, water content of dual-species biofilms decreased slowly and remained at higher levels for a longer time than mono-species C. jejuni biofilm. 27648759 2 29 theme aerobic 400:406 arg1 environment 408:418 aerobic environment 400:418 aerobic environment 400:418 The presence of C. jejuni encased in biofilms found in meat and poultry processing facilities may be the major strategy for its survival and dissemination in aerobic environment. 27648759 0 30 theme jejuni 111:116 arg1 F38011 118:123 encased Campylobacter jejuni F38011 89:123 encased Campylobacter jejuni F38011 89:123 Chemical, physical and morphological properties of bacterial biofilms affect survival of encased Campylobacter jejuni F38011 under aerobic stress. 27648759 10 31 theme C. 1644:1645 arg1 jejuni 1647:1652 mono-species C. jejuni 1631:1652 mono-species C. jejuni biofilm 1631:1660 The surface of all biofilms was hydrophilic, but total surface energy of dual-species biofilms (ranging from 52.5 to 56.2mJ/m2) was lower than that of mono-species C. jejuni biofilm, leading to more resistance to wetting by polar liquids. 27648759 5 32 theme dual-species 782:793 arg1 biofilms 795:802 some dual-species biofilms 777:802 some dual-species biofilms 777:802 In contrast, at least 4.7logCFU/cm2 of viable C. jejuni cells existed in some dual-species biofilms. 27648759 10 33 theme more 1674:1677 arg1 resistance 1679:1688 more resistance 1674:1688 more resistance to wetting by polar liquids 1674:1716 The surface of all biofilms was hydrophilic, but total surface energy of dual-species biofilms (ranging from 52.5 to 56.2mJ/m2) was lower than that of mono-species C. jejuni biofilm, leading to more resistance to wetting by polar liquids. 27648759 0 34 theme physical 10:17 arg1 properties 37:46 Chemical, physical and morphological properties 0:46 Chemical, physical and morphological properties of bacterial biofilms 0:68 Chemical, physical and morphological properties of bacterial biofilms affect survival of encased Campylobacter jejuni F38011 under aerobic stress. 27648759 9 35 theme dual-species 1356:1367 arg1 biofilms 1369:1376 dual-species biofilms 1356:1376 dual-species biofilms 1356:1376 Under desiccation stress, water content of dual-species biofilms decreased slowly and remained at higher levels for a longer time than mono-species C. jejuni biofilm. 27648759 10 36 theme biofilms 1499:1506 arg1 hydrophilic 1512:1522 hydrophilic 1512:1522 hydrophilic 1512:1522 The surface of all biofilms was hydrophilic, but total surface energy of dual-species biofilms (ranging from 52.5 to 56.2mJ/m2) was lower than that of mono-species C. jejuni biofilm, leading to more resistance to wetting by polar liquids. 27648759 10 36 theme biofilms 1499:1506 arg1 surface 1484:1490 The surface 1480:1490 The surface of all biofilms 1480:1506 The surface of all biofilms was hydrophilic, but total surface energy of dual-species biofilms (ranging from 52.5 to 56.2mJ/m2) was lower than that of mono-species C. jejuni biofilm, leading to more resistance to wetting by polar liquids. 27648759 9 37 theme mono-species 1448:1459 arg1 biofilm 1471:1477 mono-species C. jejuni biofilm 1448:1477 mono-species C. jejuni biofilm 1448:1477 Under desiccation stress, water content of dual-species biofilms decreased slowly and remained at higher levels for a longer time than mono-species C. jejuni biofilm. 27648759 0 38 theme morphological 23:35 arg1 properties 37:46 Chemical, physical and morphological properties 0:46 Chemical, physical and morphological properties of bacterial biofilms 0:68 Chemical, physical and morphological properties of bacterial biofilms affect survival of encased Campylobacter jejuni F38011 under aerobic stress. 27648759 6 39 theme protection 835:844 arg1 mode 846:849 protection mode 835:849 protection mode 835:849 To elucidate the mechanism of protection mode, chemical, physical and morphological features of biofilms were characterized. 27648759 2 40 from dissemination 383:395 arg1 environment 408:418 aerobic environment 400:418 aerobic environment 400:418 The presence of C. jejuni encased in biofilms found in meat and poultry processing facilities may be the major strategy for its survival and dissemination in aerobic environment. 27648759 10 41 theme surface 1535:1541 arg1 energy 1543:1548 total surface energy 1529:1548 total surface energy of dual-species biofilms (ranging from 52.5 to 56.2mJ/m2) 1529:1606 The surface of all biofilms was hydrophilic, but total surface energy of dual-species biofilms (ranging from 52.5 to 56.2mJ/m2) was lower than that of mono-species C. jejuni biofilm, leading to more resistance to wetting by polar liquids. 27648759 2 42 theme major 347:351 arg1 presence 246:253 The presence 242:253 The presence of C. jejuni encased in biofilms found in meat and poultry processing facilities 242:334 The presence of C. jejuni encased in biofilms found in meat and poultry processing facilities may be the major strategy for its survival and dissemination in aerobic environment. 27648759 2 42 theme major 347:351 arg1 strategy 353:360 the major strategy 343:360 the major strategy for its survival and dissemination in aerobic environment 343:418 The presence of C. jejuni encased in biofilms found in meat and poultry processing facilities may be the major strategy for its survival and dissemination in aerobic environment. 27648759 2 43 located found 288:292 arg2 biofilms 279:286 biofilms 279:286 biofilms found in meat and poultry processing facilities 279:334 The presence of C. jejuni encased in biofilms found in meat and poultry processing facilities may be the major strategy for its survival and dissemination in aerobic environment. 27648759 2 43 located found 288:292 arg1 meat 297:300 meat 297:300 meat 297:300 The presence of C. jejuni encased in biofilms found in meat and poultry processing facilities may be the major strategy for its survival and dissemination in aerobic environment. 27648759 2 43 located found 288:292 arg1 facilities 325:334 poultry processing facilities 306:334 poultry processing facilities 306:334 The presence of C. jejuni encased in biofilms found in meat and poultry processing facilities may be the major strategy for its survival and dissemination in aerobic environment. 27648759 10 44 theme biofilms 1566:1573 arg1 energy 1543:1548 total surface energy 1529:1548 total surface energy of dual-species biofilms (ranging from 52.5 to 56.2mJ/m2) 1529:1606 The surface of all biofilms was hydrophilic, but total surface energy of dual-species biofilms (ranging from 52.5 to 56.2mJ/m2) was lower than that of mono-species C. jejuni biofilm, leading to more resistance to wetting by polar liquids. 27648759 3 45 theme C. 521:522 arg1 jejuni 524:529 C. jejuni F38011 521:536 C. jejuni F38011 as a culture to form dual-species biofilms 521:579 In this study, Staphylococcus aureus, Salmonella enterica, or Pseudomonas aeruginosa was mixed with C. jejuni F38011 as a culture to form dual-species biofilms. 27648759 8 46 theme C. 1253:1254 arg1 jejuni 1256:1261 mono-species C. jejuni 1240:1261 mono-species C. jejuni biofilm 1240:1269 Structure of dual-species biofilms was more compact and their surface was >8 times smoother than mono-species C. jejuni biofilm, as indicated by atomic force microscopy. 27648759 6 47 theme biofilms 901:908 arg1 features 889:896 chemical, physical and morphological features 852:896 chemical, physical and morphological features of biofilms 852:908 To elucidate the mechanism of protection mode, chemical, physical and morphological features of biofilms were characterized. 27648759 4 48 theme aerobic 607:613 arg1 stress 615:620 aerobic stress 607:620 aerobic stress 607:620 After 4days' exposure to aerobic stress, no viable C. jejuni cells could be detected from mono-species C. jejuni biofilm. 27648759 8 49 theme dual-species 1156:1167 arg1 biofilms 1169:1176 dual-species biofilms 1156:1176 dual-species biofilms 1156:1176 Structure of dual-species biofilms was more compact and their surface was >8 times smoother than mono-species C. jejuni biofilm, as indicated by atomic force microscopy. 27648759 7 50 theme C. 1124:1125 arg1 jejuni 1127:1132 mono-species C. jejuni 1111:1132 mono-species C. jejuni biofilm 1111:1140 Dual-species biofilms contained a higher level of extracellular polymeric substances with a more diversified chemical composition, especially for polysaccharides and proteins, than mono-species C. jejuni biofilm. 27648759 1 51 theme microaerophilic 173:187 arg1 jejuni 161:166 Campylobacter jejuni 147:166 Campylobacter jejuni 147:166 Campylobacter jejuni is a microaerophilic pathogen and leading cause of human gastroenteritis. 27648759 1 51 theme microaerophilic 173:187 arg1 pathogen 189:196 a microaerophilic pathogen 171:196 a microaerophilic pathogen 171:196 Campylobacter jejuni is a microaerophilic pathogen and leading cause of human gastroenteritis. 27648759 4 52 theme jejuni 636:641 arg1 cells 643:647 no viable C. jejuni cells 623:647 no viable C. jejuni cells 623:647 After 4days' exposure to aerobic stress, no viable C. jejuni cells could be detected from mono-species C. jejuni biofilm. 27648759 3 53 theme dual-species 559:570 arg1 biofilms 572:579 dual-species biofilms 559:579 dual-species biofilms 559:579 In this study, Staphylococcus aureus, Salmonella enterica, or Pseudomonas aeruginosa was mixed with C. jejuni F38011 as a culture to form dual-species biofilms. 27648759 9 54 theme jejuni 1464:1469 arg1 biofilm 1471:1477 mono-species C. jejuni biofilm 1448:1477 mono-species C. jejuni biofilm 1448:1477 Under desiccation stress, water content of dual-species biofilms decreased slowly and remained at higher levels for a longer time than mono-species C. jejuni biofilm. 27648759 2 55 from survival 370:377 arg1 environment 408:418 aerobic environment 400:418 aerobic environment 400:418 The presence of C. jejuni encased in biofilms found in meat and poultry processing facilities may be the major strategy for its survival and dissemination in aerobic environment. 27648759 0 56 theme aerobic 131:137 arg1 stress 139:144 aerobic stress 131:144 aerobic stress 131:144 Chemical, physical and morphological properties of bacterial biofilms affect survival of encased Campylobacter jejuni F38011 under aerobic stress. 27648759 2 57 theme poultry 306:312 arg1 facilities 325:334 poultry processing facilities 306:334 poultry processing facilities 306:334 The presence of C. jejuni encased in biofilms found in meat and poultry processing facilities may be the major strategy for its survival and dissemination in aerobic environment. 27648759 7 58 contain contained 952:960 arg2 level 971:975 a higher level 962:975 a higher level of extracellular polymeric substances with a more diversified chemical composition, especially for polysaccharides and proteins 962:1103 Dual-species biofilms contained a higher level of extracellular polymeric substances with a more diversified chemical composition, especially for polysaccharides and proteins, than mono-species C. jejuni biofilm. 27648759 7 58 contain contained 952:960 arg1 biofilms 943:950 Dual-species biofilms 930:950 Dual-species biofilms 930:950 Dual-species biofilms contained a higher level of extracellular polymeric substances with a more diversified chemical composition, especially for polysaccharides and proteins, than mono-species C. jejuni biofilm. 27648759 1 59 theme human 219:223 arg1 gastroenteritis 225:239 human gastroenteritis 219:239 human gastroenteritis 219:239 Campylobacter jejuni is a microaerophilic pathogen and leading cause of human gastroenteritis. 27648759 8 60 theme atomic 1288:1293 arg1 microscopy 1301:1310 atomic force microscopy 1288:1310 atomic force microscopy 1288:1310 Structure of dual-species biofilms was more compact and their surface was >8 times smoother than mono-species C. jejuni biofilm, as indicated by atomic force microscopy. 27648759 4 61 theme viable 626:631 arg1 cells 643:647 no viable C. jejuni cells 623:647 no viable C. jejuni cells 623:647 After 4days' exposure to aerobic stress, no viable C. jejuni cells could be detected from mono-species C. jejuni biofilm. 27648759 11 62 theme jejuni 1825:1830 arg1 survival 1796:1803 survival 1796:1803 survival 1796:1803 This knowledge can aid in developing intervention strategies to decrease the survival and dispersal of C. jejuni into foods or environment. 27648759 11 62 theme jejuni 1825:1830 arg1 dispersal 1809:1817 dispersal 1809:1817 dispersal 1809:1817 This knowledge can aid in developing intervention strategies to decrease the survival and dispersal of C. jejuni into foods or environment. 27648759 8 63 theme force 1295:1299 arg1 microscopy 1301:1310 atomic force microscopy 1288:1310 atomic force microscopy 1288:1310 Structure of dual-species biofilms was more compact and their surface was >8 times smoother than mono-species C. jejuni biofilm, as indicated by atomic force microscopy. 27648759 7 64 theme diversified 1027:1037 arg1 composition 1048:1058 a more diversified chemical composition 1020:1058 a more diversified chemical composition 1020:1058 Dual-species biofilms contained a higher level of extracellular polymeric substances with a more diversified chemical composition, especially for polysaccharides and proteins, than mono-species C. jejuni biofilm. 27648759 5 65 theme 4.7logCFU/cm2 726:738 arg1 cells 760:764 at least 4.7logCFU/cm2 of viable C. jejuni cells 717:764 at least 4.7logCFU/cm2 of viable C. jejuni cells 717:764 In contrast, at least 4.7logCFU/cm2 of viable C. jejuni cells existed in some dual-species biofilms. 27648759 2 66 theme jejuni 261:266 arg1 presence 246:253 The presence 242:253 The presence of C. jejuni encased in biofilms found in meat and poultry processing facilities 242:334 The presence of C. jejuni encased in biofilms found in meat and poultry processing facilities may be the major strategy for its survival and dissemination in aerobic environment. 27648759 2 66 theme jejuni 261:266 arg1 strategy 353:360 the major strategy 343:360 the major strategy for its survival and dissemination in aerobic environment 343:418 The presence of C. jejuni encased in biofilms found in meat and poultry processing facilities may be the major strategy for its survival and dissemination in aerobic environment. 27648759 7 67 theme polymeric 994:1002 arg1 substances 1004:1013 extracellular polymeric substances 980:1013 extracellular polymeric substances 980:1013 Dual-species biofilms contained a higher level of extracellular polymeric substances with a more diversified chemical composition, especially for polysaccharides and proteins, than mono-species C. jejuni biofilm. 27648759 1 68 theme Campylobacter 147:159 arg1 jejuni 161:166 Campylobacter jejuni 147:166 Campylobacter jejuni 147:166 Campylobacter jejuni is a microaerophilic pathogen and leading cause of human gastroenteritis. 27648759 1 68 theme Campylobacter 147:159 arg1 pathogen 189:196 a microaerophilic pathogen 171:196 a microaerophilic pathogen 171:196 Campylobacter jejuni is a microaerophilic pathogen and leading cause of human gastroenteritis. 27648759 5 69 theme viable 743:748 arg1 jejuni 753:758 viable C. jejuni 743:758 viable C. jejuni 743:758 In contrast, at least 4.7logCFU/cm2 of viable C. jejuni cells existed in some dual-species biofilms. 27648759 7 70 with substances 1004:1013 arg1 composition 1048:1058 a more diversified chemical composition 1020:1058 a more diversified chemical composition 1020:1058 Dual-species biofilms contained a higher level of extracellular polymeric substances with a more diversified chemical composition, especially for polysaccharides and proteins, than mono-species C. jejuni biofilm. 27648759 4 71 theme mono-species 672:683 arg1 jejuni 688:693 mono-species C. jejuni 672:693 mono-species C. jejuni biofilm 672:701 After 4days' exposure to aerobic stress, no viable C. jejuni cells could be detected from mono-species C. jejuni biofilm. 27648759 0 72 theme Campylobacter 97:109 arg1 jejuni 111:116 encased Campylobacter jejuni 89:116 encased Campylobacter jejuni F38011 89:123 Chemical, physical and morphological properties of bacterial biofilms affect survival of encased Campylobacter jejuni F38011 under aerobic stress. 27648759 7 73 theme higher 964:969 arg1 level 971:975 a higher level 962:975 a higher level of extracellular polymeric substances with a more diversified chemical composition, especially for polysaccharides and proteins 962:1103 Dual-species biofilms contained a higher level of extracellular polymeric substances with a more diversified chemical composition, especially for polysaccharides and proteins, than mono-species C. jejuni biofilm. 27648759 11 74 theme intervention 1756:1767 arg1 strategies 1769:1778 intervention strategies 1756:1778 intervention strategies 1756:1778 This knowledge can aid in developing intervention strategies to decrease the survival and dispersal of C. jejuni into foods or environment. 27648759 0 75 theme F38011 118:123 arg1 survival 77:84 survival 77:84 survival of encased Campylobacter jejuni F38011 77:123 Chemical, physical and morphological properties of bacterial biofilms affect survival of encased Campylobacter jejuni F38011 under aerobic stress. 27648759 10 76 theme jejuni 1647:1652 arg1 biofilm 1654:1660 mono-species C. jejuni biofilm 1631:1660 mono-species C. jejuni biofilm 1631:1660 The surface of all biofilms was hydrophilic, but total surface energy of dual-species biofilms (ranging from 52.5 to 56.2mJ/m2) was lower than that of mono-species C. jejuni biofilm, leading to more resistance to wetting by polar liquids. 27648759 9 77 theme water 1339:1343 arg1 content 1345:1351 water content 1339:1351 water content of dual-species biofilms 1339:1376 Under desiccation stress, water content of dual-species biofilms decreased slowly and remained at higher levels for a longer time than mono-species C. jejuni biofilm. 27648759 7 78 theme Dual-species 930:941 arg1 biofilms 943:950 Dual-species biofilms 930:950 Dual-species biofilms 930:950 Dual-species biofilms contained a higher level of extracellular polymeric substances with a more diversified chemical composition, especially for polysaccharides and proteins, than mono-species C. jejuni biofilm. 27648759 10 79 theme mono-species 1631:1642 arg1 jejuni 1647:1652 mono-species C. jejuni 1631:1652 mono-species C. jejuni biofilm 1631:1660 The surface of all biofilms was hydrophilic, but total surface energy of dual-species biofilms (ranging from 52.5 to 56.2mJ/m2) was lower than that of mono-species C. jejuni biofilm, leading to more resistance to wetting by polar liquids. 27648759 5 80 theme jejuni 753:758 arg1 4.7logCFU/cm2 726:738 4.7logCFU/cm2 726:738 at least 4.7logCFU/cm2 of viable C. jejuni cells 717:764 In contrast, at least 4.7logCFU/cm2 of viable C. jejuni cells existed in some dual-species biofilms. 27648759 9 81 theme biofilms 1369:1376 arg1 content 1345:1351 water content 1339:1351 water content of dual-species biofilms 1339:1376 Under desiccation stress, water content of dual-species biofilms decreased slowly and remained at higher levels for a longer time than mono-species C. jejuni biofilm. 27648759 6 82 theme mode 846:849 arg1 mechanism 822:830 the mechanism 818:830 the mechanism of protection mode 818:849 To elucidate the mechanism of protection mode, chemical, physical and morphological features of biofilms were characterized. 27648759 0 83 theme bacterial 51:59 arg1 biofilms 61:68 bacterial biofilms 51:68 bacterial biofilms 51:68 Chemical, physical and morphological properties of bacterial biofilms affect survival of encased Campylobacter jejuni F38011 under aerobic stress. 27648759 10 84 theme total 1529:1533 arg1 energy 1543:1548 total surface energy 1529:1548 total surface energy of dual-species biofilms (ranging from 52.5 to 56.2mJ/m2) 1529:1606 The surface of all biofilms was hydrophilic, but total surface energy of dual-species biofilms (ranging from 52.5 to 56.2mJ/m2) was lower than that of mono-species C. jejuni biofilm, leading to more resistance to wetting by polar liquids. 27648759 9 85 theme higher 1411:1416 arg1 levels 1418:1423 higher levels 1411:1423 higher levels 1411:1423 Under desiccation stress, water content of dual-species biofilms decreased slowly and remained at higher levels for a longer time than mono-species C. jejuni biofilm. 27648759 10 86 theme dual-species 1553:1564 arg1 biofilms 1566:1573 dual-species biofilms 1553:1573 dual-species biofilms (ranging from 52.5 to 56.2mJ/m2) 1553:1606 The surface of all biofilms was hydrophilic, but total surface energy of dual-species biofilms (ranging from 52.5 to 56.2mJ/m2) was lower than that of mono-species C. jejuni biofilm, leading to more resistance to wetting by polar liquids. 24498363 9 0 theme peptide-bilayer 1347:1361 arg1 interactions 1363:1374 peptide-bilayer interactions 1347:1374 peptide-bilayer interactions 1347:1374 The studies further suggested that the first arginine is important for mediating peptide-bilayer interactions. 24498363 7 1 theme C. 1037:1038 arg1 albicans 1040:1047 C. albicans 1037:1047 C. albicans 1037:1047 We demonstrate that additives which alter the membrane potential or membrane rigidity protect C. albicans from B4010-induced lethality. 24498363 1 2 theme antifungal 160:169 arg1 activity 171:178 antifungal activity 160:178 antifungal activity 160:178 Taking advantage of the cluster effect observed in multivalent peptides, this work describes antifungal activity and possible mechanism of action of tetravalent peptide (B4010) which carries 4 copies of the sequence RGRKVVRR through a branched lysine core. 24498363 11 3 theme peptides 1611:1618 arg1 design 1574:1579 rational design 1565:1579 rational design of new tetravalent antifungal peptides 1565:1618 The combined in silico and in vitro approach should facilitate rational design of new tetravalent antifungal peptides. 24498363 4 4 theme intraperitoneal 587:601 arg1 routes 642:647 intraperitoneal (200 mg/kg) or intravenous (100 mg/kg) routes 587:647 intraperitoneal (200 mg/kg) or intravenous (100 mg/kg) routes 587:647 Moreover, B4010 is non-haemolytic and non-toxic to mice by intraperitoneal (200 mg/kg) or intravenous (100 mg/kg) routes. 24498363 8 5 theme release 1087:1093 arg1 assay 1095:1099 Calcein release assay 1079:1099 Calcein release assay 1079:1099 Calcein release assay and molecular dynamics simulations showed that the peptide preferentially binds to mixed bilayer containing ergosterol over phophotidylcholine-cholesterol bilayers. 24498363 6 6 theme ATP 908:910 arg1 release 882:888 release 882:888 release of vital ions and ATP 882:910 The peptide had no affinity for cell wall polysaccharides and caused rapid dissipation of membrane potential and release of vital ions and ATP when treated with C. albicans. 24498363 6 6 theme ATP 908:910 arg1 dissipation 844:854 rapid dissipation 838:854 rapid dissipation of membrane potential 838:876 The peptide had no affinity for cell wall polysaccharides and caused rapid dissipation of membrane potential and release of vital ions and ATP when treated with C. albicans. 24498363 10 7 theme membrane 1470:1477 arg1 properties 1490:1499 reduced membrane disruption properties 1462:1499 reduced membrane disruption properties 1462:1499 Replacing the first arginine led to a 2-4 fold decrease in antifungal activities and reduced membrane disruption properties. 24498363 2 8 theme antifungal 347:356 arg1 properties 358:367 better antifungal properties 340:367 better antifungal properties 340:367 B4010 displayed better antifungal properties than natamycin and amphotericin B. 24498363 11 9 theme new 1584:1586 arg1 peptides 1611:1618 new tetravalent antifungal peptides 1584:1618 new tetravalent antifungal peptides 1584:1618 The combined in silico and in vitro approach should facilitate rational design of new tetravalent antifungal peptides. 24498363 8 10 theme mixed 1184:1188 arg1 bilayer 1190:1196 mixed bilayer 1184:1196 mixed bilayer containing ergosterol over phophotidylcholine-cholesterol bilayers 1184:1263 Calcein release assay and molecular dynamics simulations showed that the peptide preferentially binds to mixed bilayer containing ergosterol over phophotidylcholine-cholesterol bilayers. 24498363 6 11 theme wall 806:809 arg1 polysaccharides 811:825 cell wall polysaccharides 801:825 cell wall polysaccharides 801:825 The peptide had no affinity for cell wall polysaccharides and caused rapid dissipation of membrane potential and release of vital ions and ATP when treated with C. albicans. 24498363 10 12 theme fold 1419:1422 arg1 decrease 1424:1431 a 2-4 fold decrease 1413:1431 a 2-4 fold decrease in antifungal activities and reduced membrane disruption properties 1413:1499 Replacing the first arginine led to a 2-4 fold decrease in antifungal activities and reduced membrane disruption properties. 24498363 8 13 contain containing 1198:1207 arg2 ergosterol 1209:1218 ergosterol 1209:1218 ergosterol 1209:1218 Calcein release assay and molecular dynamics simulations showed that the peptide preferentially binds to mixed bilayer containing ergosterol over phophotidylcholine-cholesterol bilayers. 24498363 8 13 contain containing 1198:1207 arg1 bilayer 1190:1196 mixed bilayer 1184:1196 mixed bilayer containing ergosterol over phophotidylcholine-cholesterol bilayers 1184:1263 Calcein release assay and molecular dynamics simulations showed that the peptide preferentially binds to mixed bilayer containing ergosterol over phophotidylcholine-cholesterol bilayers. 24498363 6 14 contain had 781:783 arg1 peptide 773:779 The peptide 769:779 The peptide 769:779 The peptide had no affinity for cell wall polysaccharides and caused rapid dissipation of membrane potential and release of vital ions and ATP when treated with C. albicans. 24498363 6 14 contain had 781:783 arg2 affinity 788:795 no affinity 785:795 no affinity for cell wall polysaccharides 785:825 The peptide had no affinity for cell wall polysaccharides and caused rapid dissipation of membrane potential and release of vital ions and ATP when treated with C. albicans. 24498363 6 15 theme ions 899:902 arg1 release 882:888 release 882:888 release of vital ions and ATP 882:910 The peptide had no affinity for cell wall polysaccharides and caused rapid dissipation of membrane potential and release of vital ions and ATP when treated with C. albicans. 24498363 6 15 theme ions 899:902 arg1 dissipation 844:854 rapid dissipation 838:854 rapid dissipation of membrane potential 838:876 The peptide had no affinity for cell wall polysaccharides and caused rapid dissipation of membrane potential and release of vital ions and ATP when treated with C. albicans. 24498363 5 16 theme cerevisiae 653:662 arg1 strains 671:677 S. cerevisiae mutant strains 650:677 S. cerevisiae mutant strains with altered membrane sterol structures and composition 650:733 S. cerevisiae mutant strains with altered membrane sterol structures and composition showed hyper senstivity to B4010. 24498363 6 17 theme cell 801:804 arg1 polysaccharides 811:825 cell wall polysaccharides 801:825 cell wall polysaccharides 801:825 The peptide had no affinity for cell wall polysaccharides and caused rapid dissipation of membrane potential and release of vital ions and ATP when treated with C. albicans. 24498363 3 18 theme tear 516:519 arg1 fluid 521:525 tear fluid 516:525 tear fluid 516:525 The peptide retained significant activity in the presence of monovalent/divalent cations, trypsin and serum and tear fluid. 24498363 11 19 theme in 1515:1516 arg1 approach 1538:1545 The combined in silico and in vitro approach 1502:1545 The combined in silico and in vitro approach 1502:1545 The combined in silico and in vitro approach should facilitate rational design of new tetravalent antifungal peptides. 24498363 5 20 theme hyper 742:746 arg1 senstivity 748:757 hyper senstivity 742:757 hyper senstivity 742:757 S. cerevisiae mutant strains with altered membrane sterol structures and composition showed hyper senstivity to B4010. 24498363 2 21 theme better 340:345 arg1 properties 358:367 better antifungal properties 340:367 better antifungal properties 340:367 B4010 displayed better antifungal properties than natamycin and amphotericin B. 24498363 8 22 theme phophotidylcholine-cholesterol 1225:1254 arg1 bilayers 1256:1263 phophotidylcholine-cholesterol bilayers 1225:1263 phophotidylcholine-cholesterol bilayers 1225:1263 Calcein release assay and molecular dynamics simulations showed that the peptide preferentially binds to mixed bilayer containing ergosterol over phophotidylcholine-cholesterol bilayers. 24498363 7 23 theme membrane 989:996 arg1 potential 998:1006 the membrane potential 985:1006 the membrane potential 985:1006 We demonstrate that additives which alter the membrane potential or membrane rigidity protect C. albicans from B4010-induced lethality. 24498363 11 24 theme combined 1506:1513 arg1 approach 1538:1545 The combined in silico and in vitro approach 1502:1545 The combined in silico and in vitro approach 1502:1545 The combined in silico and in vitro approach should facilitate rational design of new tetravalent antifungal peptides. 24498363 1 25 theme possible 184:191 arg1 mechanism 193:201 possible mechanism 184:201 possible mechanism 184:201 Taking advantage of the cluster effect observed in multivalent peptides, this work describes antifungal activity and possible mechanism of action of tetravalent peptide (B4010) which carries 4 copies of the sequence RGRKVVRR through a branched lysine core. 24498363 0 26 theme multivalent 10:20 arg1 peptides 33:40 Synthetic multivalent antifungal peptides 0:40 Synthetic multivalent antifungal peptides effective against fungi 0:64 Synthetic multivalent antifungal peptides effective against fungi. 24498363 8 27 theme Calcein 1079:1085 arg1 assay 1095:1099 Calcein release assay 1079:1099 Calcein release assay 1079:1099 Calcein release assay and molecular dynamics simulations showed that the peptide preferentially binds to mixed bilayer containing ergosterol over phophotidylcholine-cholesterol bilayers. 24498363 1 28 theme cluster 91:97 arg1 effect 99:104 the cluster effect 87:104 the cluster effect observed in multivalent peptides 87:137 Taking advantage of the cluster effect observed in multivalent peptides, this work describes antifungal activity and possible mechanism of action of tetravalent peptide (B4010) which carries 4 copies of the sequence RGRKVVRR through a branched lysine core. 24498363 6 29 theme vital 893:897 arg1 ions 899:902 vital ions 893:902 vital ions 893:902 The peptide had no affinity for cell wall polysaccharides and caused rapid dissipation of membrane potential and release of vital ions and ATP when treated with C. albicans. 24498363 2 30 theme amphotericin 388:399 arg1 B 401:401 amphotericin B 388:401 amphotericin B 388:401 B4010 displayed better antifungal properties than natamycin and amphotericin B. 24498363 0 31 theme Synthetic 0:8 arg1 peptides 33:40 Synthetic multivalent antifungal peptides 0:40 Synthetic multivalent antifungal peptides effective against fungi 0:64 Synthetic multivalent antifungal peptides effective against fungi. 24498363 10 32 from decrease 1424:1431 arg1 properties 1490:1499 reduced membrane disruption properties 1462:1499 reduced membrane disruption properties 1462:1499 Replacing the first arginine led to a 2-4 fold decrease in antifungal activities and reduced membrane disruption properties. 24498363 10 32 from decrease 1424:1431 arg1 activities 1447:1456 antifungal activities 1436:1456 antifungal activities 1436:1456 Replacing the first arginine led to a 2-4 fold decrease in antifungal activities and reduced membrane disruption properties. 24498363 1 33 theme effect 99:104 arg1 advantage 74:82 advantage 74:82 advantage of the cluster effect observed in multivalent peptides 74:137 Taking advantage of the cluster effect observed in multivalent peptides, this work describes antifungal activity and possible mechanism of action of tetravalent peptide (B4010) which carries 4 copies of the sequence RGRKVVRR through a branched lysine core. 24498363 5 34 with strains 671:677 arg1 composition 723:733 composition 723:733 composition 723:733 S. cerevisiae mutant strains with altered membrane sterol structures and composition showed hyper senstivity to B4010. 24498363 5 34 with strains 671:677 arg1 structures 708:717 altered membrane sterol structures 684:717 altered membrane sterol structures 684:717 S. cerevisiae mutant strains with altered membrane sterol structures and composition showed hyper senstivity to B4010. 24498363 1 35 theme sequence 274:281 arg1 RGRKVVRR 283:290 the sequence RGRKVVRR 270:290 the sequence RGRKVVRR 270:290 Taking advantage of the cluster effect observed in multivalent peptides, this work describes antifungal activity and possible mechanism of action of tetravalent peptide (B4010) which carries 4 copies of the sequence RGRKVVRR through a branched lysine core. 24498363 5 36 theme membrane 692:699 arg1 structures 708:717 altered membrane sterol structures 684:717 altered membrane sterol structures 684:717 S. cerevisiae mutant strains with altered membrane sterol structures and composition showed hyper senstivity to B4010. 24498363 10 37 theme disruption 1479:1488 arg1 properties 1490:1499 reduced membrane disruption properties 1462:1499 reduced membrane disruption properties 1462:1499 Replacing the first arginine led to a 2-4 fold decrease in antifungal activities and reduced membrane disruption properties. 24498363 10 38 theme first 1391:1395 arg1 arginine 1397:1404 the first arginine 1387:1404 the first arginine 1387:1404 Replacing the first arginine led to a 2-4 fold decrease in antifungal activities and reduced membrane disruption properties. 24498363 3 39 theme cations 485:491 arg1 presence 453:460 the presence 449:460 the presence of monovalent/divalent cations, trypsin and serum and tear fluid 449:525 The peptide retained significant activity in the presence of monovalent/divalent cations, trypsin and serum and tear fluid. 24498363 0 40 theme antifungal 22:31 arg1 peptides 33:40 Synthetic multivalent antifungal peptides 0:40 Synthetic multivalent antifungal peptides effective against fungi 0:64 Synthetic multivalent antifungal peptides effective against fungi. 24498363 1 41 theme RGRKVVRR 283:290 arg1 copies 260:265 4 copies 258:265 4 copies of the sequence RGRKVVRR 258:290 Taking advantage of the cluster effect observed in multivalent peptides, this work describes antifungal activity and possible mechanism of action of tetravalent peptide (B4010) which carries 4 copies of the sequence RGRKVVRR through a branched lysine core. 24498363 5 42 theme sterol 701:706 arg1 structures 708:717 altered membrane sterol structures 684:717 altered membrane sterol structures 684:717 S. cerevisiae mutant strains with altered membrane sterol structures and composition showed hyper senstivity to B4010. 24498363 11 43 theme in 1529:1530 arg1 approach 1538:1545 The combined in silico and in vitro approach 1502:1545 The combined in silico and in vitro approach 1502:1545 The combined in silico and in vitro approach should facilitate rational design of new tetravalent antifungal peptides. 24498363 7 44 theme B4010-induced 1054:1066 arg1 lethality 1068:1076 B4010-induced lethality 1054:1076 B4010-induced lethality 1054:1076 We demonstrate that additives which alter the membrane potential or membrane rigidity protect C. albicans from B4010-induced lethality. 24498363 6 45 theme potential 868:876 arg1 release 882:888 release 882:888 release of vital ions and ATP 882:910 The peptide had no affinity for cell wall polysaccharides and caused rapid dissipation of membrane potential and release of vital ions and ATP when treated with C. albicans. 24498363 6 45 theme potential 868:876 arg1 dissipation 844:854 rapid dissipation 838:854 rapid dissipation of membrane potential 838:876 The peptide had no affinity for cell wall polysaccharides and caused rapid dissipation of membrane potential and release of vital ions and ATP when treated with C. albicans. 24498363 1 46 theme tetravalent 216:226 arg1 B4010 237:241 B4010 237:241 B4010 237:241 Taking advantage of the cluster effect observed in multivalent peptides, this work describes antifungal activity and possible mechanism of action of tetravalent peptide (B4010) which carries 4 copies of the sequence RGRKVVRR through a branched lysine core. 24498363 1 46 theme tetravalent 216:226 arg1 peptide 228:234 tetravalent peptide 216:234 tetravalent peptide (B4010) 216:242 Taking advantage of the cluster effect observed in multivalent peptides, this work describes antifungal activity and possible mechanism of action of tetravalent peptide (B4010) which carries 4 copies of the sequence RGRKVVRR through a branched lysine core. 24498363 0 47 theme effective 42:50 arg1 peptides 33:40 Synthetic multivalent antifungal peptides 0:40 Synthetic multivalent antifungal peptides effective against fungi 0:64 Synthetic multivalent antifungal peptides effective against fungi. 24498363 3 48 theme significant 425:435 arg1 activity 437:444 significant activity 425:444 significant activity 425:444 The peptide retained significant activity in the presence of monovalent/divalent cations, trypsin and serum and tear fluid. 24498363 4 49 dep intraperitoneal 587:601 arg1 mg/kg 635:639 100 mg/kg 631:639 100 mg/kg 631:639 Moreover, B4010 is non-haemolytic and non-toxic to mice by intraperitoneal (200 mg/kg) or intravenous (100 mg/kg) routes. 24498363 4 49 dep intraperitoneal 587:601 arg1 mg/kg 608:612 200 mg/kg 604:612 200 mg/kg 604:612 Moreover, B4010 is non-haemolytic and non-toxic to mice by intraperitoneal (200 mg/kg) or intravenous (100 mg/kg) routes. 24498363 7 50 theme membrane 1011:1018 arg1 rigidity 1020:1027 membrane rigidity 1011:1027 membrane rigidity 1011:1027 We demonstrate that additives which alter the membrane potential or membrane rigidity protect C. albicans from B4010-induced lethality. 24498363 1 51 theme peptide 228:234 arg1 action 206:211 action 206:211 action of tetravalent peptide (B4010) 206:242 Taking advantage of the cluster effect observed in multivalent peptides, this work describes antifungal activity and possible mechanism of action of tetravalent peptide (B4010) which carries 4 copies of the sequence RGRKVVRR through a branched lysine core. 24498363 1 52 theme branched 302:309 arg1 core 318:321 a branched lysine core 300:321 a branched lysine core 300:321 Taking advantage of the cluster effect observed in multivalent peptides, this work describes antifungal activity and possible mechanism of action of tetravalent peptide (B4010) which carries 4 copies of the sequence RGRKVVRR through a branched lysine core. 24498363 5 53 theme mutant 664:669 arg1 strains 671:677 S. cerevisiae mutant strains 650:677 S. cerevisiae mutant strains with altered membrane sterol structures and composition 650:733 S. cerevisiae mutant strains with altered membrane sterol structures and composition showed hyper senstivity to B4010. 24498363 9 54 theme first 1305:1309 arg1 important 1323:1331 important 1323:1331 important 1323:1331 The studies further suggested that the first arginine is important for mediating peptide-bilayer interactions. 24498363 9 54 theme first 1305:1309 arg1 arginine 1311:1318 the first arginine 1301:1318 the first arginine 1301:1318 The studies further suggested that the first arginine is important for mediating peptide-bilayer interactions. 24498363 11 55 dep in 1515:1516 arg1 silico 1518:1523 silico 1518:1523 silico 1518:1523 The combined in silico and in vitro approach should facilitate rational design of new tetravalent antifungal peptides. 24498363 1 56 theme multivalent 118:128 arg1 peptides 130:137 multivalent peptides 118:137 multivalent peptides 118:137 Taking advantage of the cluster effect observed in multivalent peptides, this work describes antifungal activity and possible mechanism of action of tetravalent peptide (B4010) which carries 4 copies of the sequence RGRKVVRR through a branched lysine core. 24498363 1 57 theme lysine 311:316 arg1 core 318:321 a branched lysine core 300:321 a branched lysine core 300:321 Taking advantage of the cluster effect observed in multivalent peptides, this work describes antifungal activity and possible mechanism of action of tetravalent peptide (B4010) which carries 4 copies of the sequence RGRKVVRR through a branched lysine core. 24498363 8 58 theme dynamics 1115:1122 arg1 simulations 1124:1134 molecular dynamics simulations 1105:1134 molecular dynamics simulations 1105:1134 Calcein release assay and molecular dynamics simulations showed that the peptide preferentially binds to mixed bilayer containing ergosterol over phophotidylcholine-cholesterol bilayers. 24498363 6 59 theme membrane 859:866 arg1 potential 868:876 membrane potential 859:876 membrane potential 859:876 The peptide had no affinity for cell wall polysaccharides and caused rapid dissipation of membrane potential and release of vital ions and ATP when treated with C. albicans. 24498363 1 60 located observed 106:113 arg2 effect 99:104 the cluster effect 87:104 the cluster effect observed in multivalent peptides 87:137 Taking advantage of the cluster effect observed in multivalent peptides, this work describes antifungal activity and possible mechanism of action of tetravalent peptide (B4010) which carries 4 copies of the sequence RGRKVVRR through a branched lysine core. 24498363 1 60 located observed 106:113 arg1 peptides 130:137 multivalent peptides 118:137 multivalent peptides 118:137 Taking advantage of the cluster effect observed in multivalent peptides, this work describes antifungal activity and possible mechanism of action of tetravalent peptide (B4010) which carries 4 copies of the sequence RGRKVVRR through a branched lysine core. 24498363 8 61 theme molecular 1105:1113 arg1 simulations 1124:1134 molecular dynamics simulations 1105:1134 molecular dynamics simulations 1105:1134 Calcein release assay and molecular dynamics simulations showed that the peptide preferentially binds to mixed bilayer containing ergosterol over phophotidylcholine-cholesterol bilayers. 24498363 6 62 theme rapid 838:842 arg1 dissipation 844:854 rapid dissipation 838:854 rapid dissipation of membrane potential 838:876 The peptide had no affinity for cell wall polysaccharides and caused rapid dissipation of membrane potential and release of vital ions and ATP when treated with C. albicans. 24498363 10 63 theme reduced 1462:1468 arg1 properties 1490:1499 reduced membrane disruption properties 1462:1499 reduced membrane disruption properties 1462:1499 Replacing the first arginine led to a 2-4 fold decrease in antifungal activities and reduced membrane disruption properties. 24498363 5 64 theme altered 684:690 arg1 structures 708:717 altered membrane sterol structures 684:717 altered membrane sterol structures 684:717 S. cerevisiae mutant strains with altered membrane sterol structures and composition showed hyper senstivity to B4010. 24498363 10 65 theme antifungal 1436:1445 arg1 activities 1447:1456 antifungal activities 1436:1456 antifungal activities 1436:1456 Replacing the first arginine led to a 2-4 fold decrease in antifungal activities and reduced membrane disruption properties. 24498363 3 66 theme monovalent/divalent 465:483 arg1 serum 506:510 serum 506:510 serum 506:510 The peptide retained significant activity in the presence of monovalent/divalent cations, trypsin and serum and tear fluid. 24498363 3 66 theme monovalent/divalent 465:483 arg1 trypsin 494:500 trypsin 494:500 trypsin 494:500 The peptide retained significant activity in the presence of monovalent/divalent cations, trypsin and serum and tear fluid. 24498363 3 66 theme monovalent/divalent 465:483 arg1 cations 485:491 monovalent/divalent cations 465:491 monovalent/divalent cations 465:491 The peptide retained significant activity in the presence of monovalent/divalent cations, trypsin and serum and tear fluid. 24498363 11 67 theme tetravalent 1588:1598 arg1 peptides 1611:1618 new tetravalent antifungal peptides 1584:1618 new tetravalent antifungal peptides 1584:1618 The combined in silico and in vitro approach should facilitate rational design of new tetravalent antifungal peptides. 24498363 1 68 theme action 206:211 arg1 mechanism 193:201 possible mechanism 184:201 possible mechanism 184:201 Taking advantage of the cluster effect observed in multivalent peptides, this work describes antifungal activity and possible mechanism of action of tetravalent peptide (B4010) which carries 4 copies of the sequence RGRKVVRR through a branched lysine core. 24498363 1 68 theme action 206:211 arg1 activity 171:178 antifungal activity 160:178 antifungal activity 160:178 Taking advantage of the cluster effect observed in multivalent peptides, this work describes antifungal activity and possible mechanism of action of tetravalent peptide (B4010) which carries 4 copies of the sequence RGRKVVRR through a branched lysine core. 24498363 11 69 theme rational 1565:1572 arg1 design 1574:1579 rational design 1565:1579 rational design of new tetravalent antifungal peptides 1565:1618 The combined in silico and in vitro approach should facilitate rational design of new tetravalent antifungal peptides. 24498363 4 70 theme intravenous 618:628 arg1 routes 642:647 intraperitoneal (200 mg/kg) or intravenous (100 mg/kg) routes 587:647 intraperitoneal (200 mg/kg) or intravenous (100 mg/kg) routes 587:647 Moreover, B4010 is non-haemolytic and non-toxic to mice by intraperitoneal (200 mg/kg) or intravenous (100 mg/kg) routes. 24498363 11 71 dep in 1529:1530 arg1 vitro 1532:1536 vitro 1532:1536 vitro 1532:1536 The combined in silico and in vitro approach should facilitate rational design of new tetravalent antifungal peptides. 24498363 1 72 contain carries 250:256 arg1 mechanism 193:201 possible mechanism 184:201 possible mechanism 184:201 Taking advantage of the cluster effect observed in multivalent peptides, this work describes antifungal activity and possible mechanism of action of tetravalent peptide (B4010) which carries 4 copies of the sequence RGRKVVRR through a branched lysine core. 24498363 1 72 contain carries 250:256 arg2 copies 260:265 4 copies 258:265 4 copies of the sequence RGRKVVRR 258:290 Taking advantage of the cluster effect observed in multivalent peptides, this work describes antifungal activity and possible mechanism of action of tetravalent peptide (B4010) which carries 4 copies of the sequence RGRKVVRR through a branched lysine core. 24498363 1 72 contain carries 250:256 arg1 activity 171:178 antifungal activity 160:178 antifungal activity 160:178 Taking advantage of the cluster effect observed in multivalent peptides, this work describes antifungal activity and possible mechanism of action of tetravalent peptide (B4010) which carries 4 copies of the sequence RGRKVVRR through a branched lysine core. 24498363 11 73 theme antifungal 1600:1609 arg1 peptides 1611:1618 new tetravalent antifungal peptides 1584:1618 new tetravalent antifungal peptides 1584:1618 The combined in silico and in vitro approach should facilitate rational design of new tetravalent antifungal peptides. 26264896 7 0 theme cell 1182:1185 arg1 membranes 1194:1202 Hofbauer cell plasma membranes 1173:1202 Hofbauer cell plasma membranes 1173:1202 Glycan profiles were obtained for Hofbauer cell plasma membranes, cytosol, lysosomes and small granules. 26264896 10 1 from evident 1573:1579 arg1 half 1594:1597 the first half 1584:1597 the first half of pregnancy 1584:1610 DISCUSSION Hofbauer cells have properties commensurate with their phagocytic activity with numerous lysosomal vacuoles and heavily glycosylated plasma membranes and granules, most evident in the first half of pregnancy. 26264896 6 2 from present 1039:1045 arg1 cells 1054:1058 the cells 1050:1058 the cells 1050:1058 Lectin histochemistry showed that many classes of glycan were present in the cells, both N and O-linked, though simple fucose residues could not be demonstrated. 26264896 2 3 theme placentae 251:259 arg1 Sections 239:246 MATERIALS AND METHODS Sections 217:246 MATERIALS AND METHODS Sections of placentae from 6 weeks to term 217:280 MATERIALS AND METHODS Sections of placentae from 6 weeks to term were stained with antibodies to α-amylase, glycogen synthase, glycogen phosphorylase and glucose transporters 1 and 3 (GLUT-1 and GLUT-3) while a panel of 24 lectins was applied to resin sections from 4 weeks onwards. 26264896 10 4 theme plasma 1537:1542 arg1 membranes 1544:1552 heavily glycosylated plasma membranes 1516:1552 heavily glycosylated plasma membranes 1516:1552 DISCUSSION Hofbauer cells have properties commensurate with their phagocytic activity with numerous lysosomal vacuoles and heavily glycosylated plasma membranes and granules, most evident in the first half of pregnancy. 26264896 9 5 theme pregnancy 1382:1390 arg1 course 1372:1377 the course 1368:1377 the course of pregnancy 1368:1390 Morphological changes also occurred over the course of pregnancy. 26264896 10 6 from half 1594:1597 arg1 evident 1573:1579 evident 1573:1579 evident 1573:1579 DISCUSSION Hofbauer cells have properties commensurate with their phagocytic activity with numerous lysosomal vacuoles and heavily glycosylated plasma membranes and granules, most evident in the first half of pregnancy. 26264896 6 7 theme fucose 1096:1101 arg1 residues 1103:1110 simple fucose residues 1089:1110 simple fucose residues 1089:1110 Lectin histochemistry showed that many classes of glycan were present in the cells, both N and O-linked, though simple fucose residues could not be demonstrated. 26264896 4 8 theme simplicifolia-II 638:653 arg1 binding 666:672 Bandeiraea simplicifolia-II agglutinin binding 627:672 Bandeiraea simplicifolia-II agglutinin binding 627:672 RESULTS Little stored glycogen could be demonstrated by Bandeiraea simplicifolia-II agglutinin binding and, by immunocytochemistry, low levels of glycogen synthase were located within the cells, though glycogen phosphorylase expression, an enzyme releasing glucose from glycogen chains, was intense. 26264896 10 9 theme evident 1573:1579 arg1 membranes 1544:1552 heavily glycosylated plasma membranes 1516:1552 heavily glycosylated plasma membranes 1516:1552 DISCUSSION Hofbauer cells have properties commensurate with their phagocytic activity with numerous lysosomal vacuoles and heavily glycosylated plasma membranes and granules, most evident in the first half of pregnancy. 26264896 2 10 theme glucose 371:377 arg1 antibodies 300:309 antibodies 300:309 antibodies to α-amylase 300:322 MATERIALS AND METHODS Sections of placentae from 6 weeks to term were stained with antibodies to α-amylase, glycogen synthase, glycogen phosphorylase and glucose transporters 1 and 3 (GLUT-1 and GLUT-3) while a panel of 24 lectins was applied to resin sections from 4 weeks onwards. 26264896 2 10 theme glucose 371:377 arg1 transporters 379:390 glucose transporters 1 and 3 (GLUT-1 and GLUT-3) 371:418 glucose transporters 1 and 3 (GLUT-1 and GLUT-3) 371:418 MATERIALS AND METHODS Sections of placentae from 6 weeks to term were stained with antibodies to α-amylase, glycogen synthase, glycogen phosphorylase and glucose transporters 1 and 3 (GLUT-1 and GLUT-3) while a panel of 24 lectins was applied to resin sections from 4 weeks onwards. 26264896 1 11 gly glycosylation 133:145 arg1 macrophages 158:168 villous macrophages 150:168 villous macrophages (Hofbauer cells) 150:185 INTRODUCTION This study examines the glucose metabolism and glycosylation of villous macrophages (Hofbauer cells) over the course of pregnancy. 26264896 1 11 gly glycosylation 133:145 arg1 cells 180:184 Hofbauer cells 171:184 Hofbauer cells 171:184 INTRODUCTION This study examines the glucose metabolism and glycosylation of villous macrophages (Hofbauer cells) over the course of pregnancy. 26264896 2 12 theme METHODS 231:237 arg1 Sections 239:246 MATERIALS AND METHODS Sections 217:246 MATERIALS AND METHODS Sections of placentae from 6 weeks to term 217:280 MATERIALS AND METHODS Sections of placentae from 6 weeks to term were stained with antibodies to α-amylase, glycogen synthase, glycogen phosphorylase and glucose transporters 1 and 3 (GLUT-1 and GLUT-3) while a panel of 24 lectins was applied to resin sections from 4 weeks onwards. 26264896 5 13 attach present 908:914 arg1 cells 923:927 the cells 919:927 the cells 919:927 Glucose transporter-3 but not -1 was present in the cells as has been found in other types of macrophage. 26264896 5 13 attach present 908:914 arg2 transporter-3 879:891 Glucose transporter-3 871:891 Glucose transporter-3 but not -1 871:902 Glucose transporter-3 but not -1 was present in the cells as has been found in other types of macrophage. 26264896 5 13 attach present 908:914 arg2 -1 901:902 -1 901:902 -1 901:902 Glucose transporter-3 but not -1 was present in the cells as has been found in other types of macrophage. 26264896 1 14 dep INTRODUCTION 73:84 arg1 examines 97:104 examines 97:104 examines the glucose metabolism and glycosylation of villous macrophages (Hofbauer cells) over the course of pregnancy 97:214 INTRODUCTION This study examines the glucose metabolism and glycosylation of villous macrophages (Hofbauer cells) over the course of pregnancy. 26264896 2 15 theme MATERIALS 217:225 arg1 Sections 239:246 MATERIALS AND METHODS Sections 217:246 MATERIALS AND METHODS Sections of placentae from 6 weeks to term 217:280 MATERIALS AND METHODS Sections of placentae from 6 weeks to term were stained with antibodies to α-amylase, glycogen synthase, glycogen phosphorylase and glucose transporters 1 and 3 (GLUT-1 and GLUT-3) while a panel of 24 lectins was applied to resin sections from 4 weeks onwards. 26264896 4 16 theme low 703:705 arg1 levels 707:712 low levels 703:712 low levels of glycogen synthase 703:733 RESULTS Little stored glycogen could be demonstrated by Bandeiraea simplicifolia-II agglutinin binding and, by immunocytochemistry, low levels of glycogen synthase were located within the cells, though glycogen phosphorylase expression, an enzyme releasing glucose from glycogen chains, was intense. 26264896 6 17 theme Lectin 977:982 arg1 histochemistry 984:997 Lectin histochemistry 977:997 Lectin histochemistry 977:997 Lectin histochemistry showed that many classes of glycan were present in the cells, both N and O-linked, though simple fucose residues could not be demonstrated. 26264896 2 18 theme resin 463:467 arg1 sections 469:476 resin sections 463:476 resin sections from 4 weeks onwards 463:497 MATERIALS AND METHODS Sections of placentae from 6 weeks to term were stained with antibodies to α-amylase, glycogen synthase, glycogen phosphorylase and glucose transporters 1 and 3 (GLUT-1 and GLUT-3) while a panel of 24 lectins was applied to resin sections from 4 weeks onwards. 26264896 10 19 gly glycosylated 1524:1535 arg1 membranes 1544:1552 heavily glycosylated plasma membranes 1516:1552 heavily glycosylated plasma membranes 1516:1552 DISCUSSION Hofbauer cells have properties commensurate with their phagocytic activity with numerous lysosomal vacuoles and heavily glycosylated plasma membranes and granules, most evident in the first half of pregnancy. 26264896 10 20 with commensurate 1435:1446 arg1 activity 1470:1477 their phagocytic activity 1453:1477 their phagocytic activity with numerous lysosomal vacuoles and heavily glycosylated plasma membranes and granules, most evident in the first half of pregnancy 1453:1610 DISCUSSION Hofbauer cells have properties commensurate with their phagocytic activity with numerous lysosomal vacuoles and heavily glycosylated plasma membranes and granules, most evident in the first half of pregnancy. 26264896 7 21 theme Hofbauer 1173:1180 arg1 membranes 1194:1202 Hofbauer cell plasma membranes 1173:1202 Hofbauer cell plasma membranes 1173:1202 Glycan profiles were obtained for Hofbauer cell plasma membranes, cytosol, lysosomes and small granules. 26264896 1 22 theme macrophages 158:168 arg1 glycosylation 133:145 glycosylation 133:145 glycosylation 133:145 INTRODUCTION This study examines the glucose metabolism and glycosylation of villous macrophages (Hofbauer cells) over the course of pregnancy. 26264896 1 22 theme macrophages 158:168 arg1 metabolism 118:127 glucose metabolism 110:127 glucose metabolism 110:127 INTRODUCTION This study examines the glucose metabolism and glycosylation of villous macrophages (Hofbauer cells) over the course of pregnancy. 26264896 10 23 theme DISCUSSION 1393:1402 arg1 cells 1413:1417 DISCUSSION Hofbauer cells 1393:1417 DISCUSSION Hofbauer cells 1393:1417 DISCUSSION Hofbauer cells have properties commensurate with their phagocytic activity with numerous lysosomal vacuoles and heavily glycosylated plasma membranes and granules, most evident in the first half of pregnancy. 26264896 11 24 theme existence 1753:1761 arg1 mode 1745:1748 their peripatetic mode 1727:1748 their peripatetic mode of existence 1727:1761 Their carbohydrate metabolism appears to rely on glucose mobilisation rather than storage as glycogen, reflecting their peripatetic mode of existence. 26264896 1 25 theme Hofbauer 171:178 arg1 macrophages 158:168 villous macrophages 150:168 villous macrophages (Hofbauer cells) 150:185 INTRODUCTION This study examines the glucose metabolism and glycosylation of villous macrophages (Hofbauer cells) over the course of pregnancy. 26264896 1 25 theme Hofbauer 171:178 arg1 cells 180:184 Hofbauer cells 171:184 Hofbauer cells 171:184 INTRODUCTION This study examines the glucose metabolism and glycosylation of villous macrophages (Hofbauer cells) over the course of pregnancy. 26264896 2 26 theme weeks 485:489 arg1 onwards 491:497 4 weeks onwards 483:497 4 weeks onwards 483:497 MATERIALS AND METHODS Sections of placentae from 6 weeks to term were stained with antibodies to α-amylase, glycogen synthase, glycogen phosphorylase and glucose transporters 1 and 3 (GLUT-1 and GLUT-3) while a panel of 24 lectins was applied to resin sections from 4 weeks onwards. 26264896 4 27 theme glycogen 717:724 arg1 synthase 726:733 glycogen synthase 717:733 glycogen synthase 717:733 RESULTS Little stored glycogen could be demonstrated by Bandeiraea simplicifolia-II agglutinin binding and, by immunocytochemistry, low levels of glycogen synthase were located within the cells, though glycogen phosphorylase expression, an enzyme releasing glucose from glycogen chains, was intense. 26264896 6 28 located present 1039:1045 arg1 cells 1054:1058 the cells 1050:1058 the cells 1050:1058 Lectin histochemistry showed that many classes of glycan were present in the cells, both N and O-linked, though simple fucose residues could not be demonstrated. 26264896 6 28 located present 1039:1045 arg2 classes 1016:1022 many classes 1011:1022 many classes of glycan 1011:1032 Lectin histochemistry showed that many classes of glycan were present in the cells, both N and O-linked, though simple fucose residues could not be demonstrated. 26264896 1 29 dep metabolism 118:127 arg1 the 106:108 the 106:108 the 106:108 INTRODUCTION This study examines the glucose metabolism and glycosylation of villous macrophages (Hofbauer cells) over the course of pregnancy. 26264896 0 30 theme Functional 0:9 arg1 changes 11:17 Functional changes 0:17 Functional changes in Hofbauer cell glycobiology during human pregnancy 0:70 Functional changes in Hofbauer cell glycobiology during human pregnancy. 26264896 4 31 located located 740:746 arg2 levels 707:712 low levels 703:712 low levels of glycogen synthase 703:733 RESULTS Little stored glycogen could be demonstrated by Bandeiraea simplicifolia-II agglutinin binding and, by immunocytochemistry, low levels of glycogen synthase were located within the cells, though glycogen phosphorylase expression, an enzyme releasing glucose from glycogen chains, was intense. 26264896 4 31 located located 740:746 arg1 cells 759:763 the cells 755:763 the cells 755:763 RESULTS Little stored glycogen could be demonstrated by Bandeiraea simplicifolia-II agglutinin binding and, by immunocytochemistry, low levels of glycogen synthase were located within the cells, though glycogen phosphorylase expression, an enzyme releasing glucose from glycogen chains, was intense. 26264896 10 32 theme phagocytic 1459:1468 arg1 activity 1470:1477 their phagocytic activity 1453:1477 their phagocytic activity with numerous lysosomal vacuoles and heavily glycosylated plasma membranes and granules, most evident in the first half of pregnancy 1453:1610 DISCUSSION Hofbauer cells have properties commensurate with their phagocytic activity with numerous lysosomal vacuoles and heavily glycosylated plasma membranes and granules, most evident in the first half of pregnancy. 26264896 4 33 theme synthase 726:733 arg1 levels 707:712 low levels 703:712 low levels of glycogen synthase 703:733 RESULTS Little stored glycogen could be demonstrated by Bandeiraea simplicifolia-II agglutinin binding and, by immunocytochemistry, low levels of glycogen synthase were located within the cells, though glycogen phosphorylase expression, an enzyme releasing glucose from glycogen chains, was intense. 26264896 1 34 theme glucose 110:116 arg1 metabolism 118:127 glucose metabolism 110:127 glucose metabolism 110:127 INTRODUCTION This study examines the glucose metabolism and glycosylation of villous macrophages (Hofbauer cells) over the course of pregnancy. 26264896 6 35 theme many 1011:1014 arg1 classes 1016:1022 many classes 1011:1022 many classes of glycan 1011:1032 Lectin histochemistry showed that many classes of glycan were present in the cells, both N and O-linked, though simple fucose residues could not be demonstrated. 26264896 2 36 theme lectins 440:446 arg1 panel 428:432 a panel 426:432 a panel of 24 lectins 426:446 MATERIALS AND METHODS Sections of placentae from 6 weeks to term were stained with antibodies to α-amylase, glycogen synthase, glycogen phosphorylase and glucose transporters 1 and 3 (GLUT-1 and GLUT-3) while a panel of 24 lectins was applied to resin sections from 4 weeks onwards. 26264896 0 37 theme cell 31:34 arg1 glycobiology 36:47 Hofbauer cell glycobiology 22:47 Hofbauer cell glycobiology 22:47 Functional changes in Hofbauer cell glycobiology during human pregnancy. 26264896 10 38 theme lysosomal 1493:1501 arg1 vacuoles 1503:1510 numerous lysosomal vacuoles 1484:1510 numerous lysosomal vacuoles 1484:1510 DISCUSSION Hofbauer cells have properties commensurate with their phagocytic activity with numerous lysosomal vacuoles and heavily glycosylated plasma membranes and granules, most evident in the first half of pregnancy. 26264896 11 39 theme glucose 1662:1668 arg1 mobilisation 1670:1681 glucose mobilisation 1662:1681 glucose mobilisation rather than storage 1662:1701 Their carbohydrate metabolism appears to rely on glucose mobilisation rather than storage as glycogen, reflecting their peripatetic mode of existence. 26264896 2 40 dep transporters 379:390 arg1 1 392:392 1 392:392 1 392:392 MATERIALS AND METHODS Sections of placentae from 6 weeks to term were stained with antibodies to α-amylase, glycogen synthase, glycogen phosphorylase and glucose transporters 1 and 3 (GLUT-1 and GLUT-3) while a panel of 24 lectins was applied to resin sections from 4 weeks onwards. 26264896 2 40 dep transporters 379:390 arg1 3 398:398 3 398:398 3 398:398 MATERIALS AND METHODS Sections of placentae from 6 weeks to term were stained with antibodies to α-amylase, glycogen synthase, glycogen phosphorylase and glucose transporters 1 and 3 (GLUT-1 and GLUT-3) while a panel of 24 lectins was applied to resin sections from 4 weeks onwards. 26264896 2 41 dep 3 398:398 arg1 GLUT-3 412:417 GLUT-3 412:417 GLUT-3 412:417 MATERIALS AND METHODS Sections of placentae from 6 weeks to term were stained with antibodies to α-amylase, glycogen synthase, glycogen phosphorylase and glucose transporters 1 and 3 (GLUT-1 and GLUT-3) while a panel of 24 lectins was applied to resin sections from 4 weeks onwards. 26264896 2 41 dep 3 398:398 arg1 GLUT-1 401:406 GLUT-1 401:406 GLUT-1 401:406 MATERIALS AND METHODS Sections of placentae from 6 weeks to term were stained with antibodies to α-amylase, glycogen synthase, glycogen phosphorylase and glucose transporters 1 and 3 (GLUT-1 and GLUT-3) while a panel of 24 lectins was applied to resin sections from 4 weeks onwards. 26264896 5 42 from cells 923:927 arg1 present 908:914 present 908:914 present 908:914 Glucose transporter-3 but not -1 was present in the cells as has been found in other types of macrophage. 26264896 5 43 theme other 950:954 arg1 types 956:960 other types 950:960 other types of macrophage 950:974 Glucose transporter-3 but not -1 was present in the cells as has been found in other types of macrophage. 26264896 2 44 from onwards 491:497 arg1 sections 469:476 resin sections 463:476 resin sections from 4 weeks onwards 463:497 MATERIALS AND METHODS Sections of placentae from 6 weeks to term were stained with antibodies to α-amylase, glycogen synthase, glycogen phosphorylase and glucose transporters 1 and 3 (GLUT-1 and GLUT-3) while a panel of 24 lectins was applied to resin sections from 4 weeks onwards. 26264896 10 45 theme glycosylated 1524:1535 arg1 membranes 1544:1552 heavily glycosylated plasma membranes 1516:1552 heavily glycosylated plasma membranes 1516:1552 DISCUSSION Hofbauer cells have properties commensurate with their phagocytic activity with numerous lysosomal vacuoles and heavily glycosylated plasma membranes and granules, most evident in the first half of pregnancy. 26264896 4 46 theme glycogen 773:780 arg1 expression 796:805 glycogen phosphorylase expression 773:805 glycogen phosphorylase expression 773:805 RESULTS Little stored glycogen could be demonstrated by Bandeiraea simplicifolia-II agglutinin binding and, by immunocytochemistry, low levels of glycogen synthase were located within the cells, though glycogen phosphorylase expression, an enzyme releasing glucose from glycogen chains, was intense. 26264896 4 46 theme glycogen 773:780 arg1 enzyme 811:816 an enzyme 808:816 an enzyme releasing glucose from glycogen chains 808:855 RESULTS Little stored glycogen could be demonstrated by Bandeiraea simplicifolia-II agglutinin binding and, by immunocytochemistry, low levels of glycogen synthase were located within the cells, though glycogen phosphorylase expression, an enzyme releasing glucose from glycogen chains, was intense. 26264896 4 47 theme RESULTS 571:577 arg1 glycogen 593:600 RESULTS Little stored glycogen 571:600 RESULTS Little stored glycogen 571:600 RESULTS Little stored glycogen could be demonstrated by Bandeiraea simplicifolia-II agglutinin binding and, by immunocytochemistry, low levels of glycogen synthase were located within the cells, though glycogen phosphorylase expression, an enzyme releasing glucose from glycogen chains, was intense. 26264896 11 48 theme carbohydrate 1619:1630 arg1 metabolism 1632:1641 Their carbohydrate metabolism 1613:1641 Their carbohydrate metabolism 1613:1641 Their carbohydrate metabolism appears to rely on glucose mobilisation rather than storage as glycogen, reflecting their peripatetic mode of existence. 26264896 6 49 from cells 1054:1058 arg1 present 1039:1045 present 1039:1045 present 1039:1045 Lectin histochemistry showed that many classes of glycan were present in the cells, both N and O-linked, though simple fucose residues could not be demonstrated. 26264896 2 50 theme glycogen 344:351 arg1 antibodies 300:309 antibodies 300:309 antibodies to α-amylase 300:322 MATERIALS AND METHODS Sections of placentae from 6 weeks to term were stained with antibodies to α-amylase, glycogen synthase, glycogen phosphorylase and glucose transporters 1 and 3 (GLUT-1 and GLUT-3) while a panel of 24 lectins was applied to resin sections from 4 weeks onwards. 26264896 2 50 theme glycogen 344:351 arg1 phosphorylase 353:365 glycogen phosphorylase 344:365 glycogen phosphorylase 344:365 MATERIALS AND METHODS Sections of placentae from 6 weeks to term were stained with antibodies to α-amylase, glycogen synthase, glycogen phosphorylase and glucose transporters 1 and 3 (GLUT-1 and GLUT-3) while a panel of 24 lectins was applied to resin sections from 4 weeks onwards. 26264896 4 51 theme glycogen 841:848 arg1 chains 850:855 glycogen chains 841:855 glycogen chains 841:855 RESULTS Little stored glycogen could be demonstrated by Bandeiraea simplicifolia-II agglutinin binding and, by immunocytochemistry, low levels of glycogen synthase were located within the cells, though glycogen phosphorylase expression, an enzyme releasing glucose from glycogen chains, was intense. 26264896 7 52 theme plasma 1187:1192 arg1 membranes 1194:1202 Hofbauer cell plasma membranes 1173:1202 Hofbauer cell plasma membranes 1173:1202 Glycan profiles were obtained for Hofbauer cell plasma membranes, cytosol, lysosomes and small granules. 26264896 3 53 theme Hofbauer 500:507 arg1 cells 509:513 Hofbauer cells 500:513 Hofbauer cells 500:513 Hofbauer cells were identified by the binding of anti-CD 163 antibody. 26264896 6 54 attach present 1039:1045 arg1 cells 1054:1058 the cells 1050:1058 the cells 1050:1058 Lectin histochemistry showed that many classes of glycan were present in the cells, both N and O-linked, though simple fucose residues could not be demonstrated. 26264896 6 54 attach present 1039:1045 arg2 classes 1016:1022 many classes 1011:1022 many classes of glycan 1011:1032 Lectin histochemistry showed that many classes of glycan were present in the cells, both N and O-linked, though simple fucose residues could not be demonstrated. 26264896 10 55 with activity 1470:1477 arg1 membranes 1544:1552 heavily glycosylated plasma membranes 1516:1552 heavily glycosylated plasma membranes 1516:1552 DISCUSSION Hofbauer cells have properties commensurate with their phagocytic activity with numerous lysosomal vacuoles and heavily glycosylated plasma membranes and granules, most evident in the first half of pregnancy. 26264896 10 55 with activity 1470:1477 arg1 vacuoles 1503:1510 numerous lysosomal vacuoles 1484:1510 numerous lysosomal vacuoles 1484:1510 DISCUSSION Hofbauer cells have properties commensurate with their phagocytic activity with numerous lysosomal vacuoles and heavily glycosylated plasma membranes and granules, most evident in the first half of pregnancy. 26264896 6 56 theme simple 1089:1094 arg1 residues 1103:1110 simple fucose residues 1089:1110 simple fucose residues 1089:1110 Lectin histochemistry showed that many classes of glycan were present in the cells, both N and O-linked, though simple fucose residues could not be demonstrated. 26264896 4 57 theme Bandeiraea 627:636 arg1 binding 666:672 Bandeiraea simplicifolia-II agglutinin binding 627:672 Bandeiraea simplicifolia-II agglutinin binding 627:672 RESULTS Little stored glycogen could be demonstrated by Bandeiraea simplicifolia-II agglutinin binding and, by immunocytochemistry, low levels of glycogen synthase were located within the cells, though glycogen phosphorylase expression, an enzyme releasing glucose from glycogen chains, was intense. 26264896 4 58 theme stored 586:591 arg1 glycogen 593:600 RESULTS Little stored glycogen 571:600 RESULTS Little stored glycogen 571:600 RESULTS Little stored glycogen could be demonstrated by Bandeiraea simplicifolia-II agglutinin binding and, by immunocytochemistry, low levels of glycogen synthase were located within the cells, though glycogen phosphorylase expression, an enzyme releasing glucose from glycogen chains, was intense. 26264896 3 59 theme anti-CD 549:555 arg1 antibody 561:568 anti-CD 163 antibody 549:568 anti-CD 163 antibody 549:568 Hofbauer cells were identified by the binding of anti-CD 163 antibody. 26264896 10 60 contain have 1419:1422 arg2 properties 1424:1433 properties 1424:1433 properties commensurate with their phagocytic activity with numerous lysosomal vacuoles and heavily glycosylated plasma membranes and granules, most evident in the first half of pregnancy 1424:1610 DISCUSSION Hofbauer cells have properties commensurate with their phagocytic activity with numerous lysosomal vacuoles and heavily glycosylated plasma membranes and granules, most evident in the first half of pregnancy. 26264896 10 60 contain have 1419:1422 arg1 cells 1413:1417 DISCUSSION Hofbauer cells 1393:1417 DISCUSSION Hofbauer cells 1393:1417 DISCUSSION Hofbauer cells have properties commensurate with their phagocytic activity with numerous lysosomal vacuoles and heavily glycosylated plasma membranes and granules, most evident in the first half of pregnancy. 26264896 10 61 theme first 1588:1592 arg1 half 1594:1597 the first half 1584:1597 the first half of pregnancy 1584:1610 DISCUSSION Hofbauer cells have properties commensurate with their phagocytic activity with numerous lysosomal vacuoles and heavily glycosylated plasma membranes and granules, most evident in the first half of pregnancy. 26264896 2 62 from weeks 268:272 arg1 Sections 239:246 MATERIALS AND METHODS Sections 217:246 MATERIALS AND METHODS Sections of placentae from 6 weeks to term 217:280 MATERIALS AND METHODS Sections of placentae from 6 weeks to term were stained with antibodies to α-amylase, glycogen synthase, glycogen phosphorylase and glucose transporters 1 and 3 (GLUT-1 and GLUT-3) while a panel of 24 lectins was applied to resin sections from 4 weeks onwards. 26264896 11 63 theme peripatetic 1733:1743 arg1 mode 1745:1748 their peripatetic mode 1727:1748 their peripatetic mode of existence 1727:1761 Their carbohydrate metabolism appears to rely on glucose mobilisation rather than storage as glycogen, reflecting their peripatetic mode of existence. 26264896 3 64 theme antibody 561:568 arg1 binding 538:544 the binding 534:544 the binding of anti-CD 163 antibody 534:568 Hofbauer cells were identified by the binding of anti-CD 163 antibody. 26264896 1 65 theme villous 150:156 arg1 macrophages 158:168 villous macrophages 150:168 villous macrophages (Hofbauer cells) 150:185 INTRODUCTION This study examines the glucose metabolism and glycosylation of villous macrophages (Hofbauer cells) over the course of pregnancy. 26264896 1 65 theme villous 150:156 arg1 cells 180:184 Hofbauer cells 171:184 Hofbauer cells 171:184 INTRODUCTION This study examines the glucose metabolism and glycosylation of villous macrophages (Hofbauer cells) over the course of pregnancy. 26264896 4 66 theme agglutinin 655:664 arg1 binding 666:672 Bandeiraea simplicifolia-II agglutinin binding 627:672 Bandeiraea simplicifolia-II agglutinin binding 627:672 RESULTS Little stored glycogen could be demonstrated by Bandeiraea simplicifolia-II agglutinin binding and, by immunocytochemistry, low levels of glycogen synthase were located within the cells, though glycogen phosphorylase expression, an enzyme releasing glucose from glycogen chains, was intense. 26264896 5 67 theme Glucose 871:877 arg1 transporter-3 879:891 Glucose transporter-3 871:891 Glucose transporter-3 but not -1 871:902 Glucose transporter-3 but not -1 was present in the cells as has been found in other types of macrophage. 26264896 4 68 attach releasing 818:826 arg2 enzyme 811:816 an enzyme 808:816 an enzyme releasing glucose from glycogen chains 808:855 RESULTS Little stored glycogen could be demonstrated by Bandeiraea simplicifolia-II agglutinin binding and, by immunocytochemistry, low levels of glycogen synthase were located within the cells, though glycogen phosphorylase expression, an enzyme releasing glucose from glycogen chains, was intense. 26264896 4 68 attach releasing 818:826 arg2 expression 796:805 glycogen phosphorylase expression 773:805 glycogen phosphorylase expression 773:805 RESULTS Little stored glycogen could be demonstrated by Bandeiraea simplicifolia-II agglutinin binding and, by immunocytochemistry, low levels of glycogen synthase were located within the cells, though glycogen phosphorylase expression, an enzyme releasing glucose from glycogen chains, was intense. 26264896 4 68 attach releasing 818:826 arg1 chains 850:855 glycogen chains 841:855 glycogen chains 841:855 RESULTS Little stored glycogen could be demonstrated by Bandeiraea simplicifolia-II agglutinin binding and, by immunocytochemistry, low levels of glycogen synthase were located within the cells, though glycogen phosphorylase expression, an enzyme releasing glucose from glycogen chains, was intense. 26264896 0 69 from changes 11:17 arg1 glycobiology 36:47 Hofbauer cell glycobiology 22:47 Hofbauer cell glycobiology 22:47 Functional changes in Hofbauer cell glycobiology during human pregnancy. 26264896 7 70 theme Glycan 1139:1144 arg1 profiles 1146:1153 Glycan profiles 1139:1153 Glycan profiles 1139:1153 Glycan profiles were obtained for Hofbauer cell plasma membranes, cytosol, lysosomes and small granules. 26264896 8 71 theme binding 1280:1286 arg1 intensity 1267:1275 the intensity 1263:1275 the intensity of binding 1263:1286 With some lectins, the intensity of binding diminished after the second trimester. 26264896 6 72 theme glycan 1027:1032 arg1 classes 1016:1022 many classes 1011:1022 many classes of glycan 1011:1032 Lectin histochemistry showed that many classes of glycan were present in the cells, both N and O-linked, though simple fucose residues could not be demonstrated. 26264896 10 73 theme Hofbauer 1404:1411 arg1 cells 1413:1417 DISCUSSION Hofbauer cells 1393:1417 DISCUSSION Hofbauer cells 1393:1417 DISCUSSION Hofbauer cells have properties commensurate with their phagocytic activity with numerous lysosomal vacuoles and heavily glycosylated plasma membranes and granules, most evident in the first half of pregnancy. 26264896 10 74 theme pregnancy 1602:1610 arg1 half 1594:1597 the first half 1584:1597 the first half of pregnancy 1584:1610 DISCUSSION Hofbauer cells have properties commensurate with their phagocytic activity with numerous lysosomal vacuoles and heavily glycosylated plasma membranes and granules, most evident in the first half of pregnancy. 26264896 0 75 theme Hofbauer 22:29 arg1 glycobiology 36:47 Hofbauer cell glycobiology 22:47 Hofbauer cell glycobiology 22:47 Functional changes in Hofbauer cell glycobiology during human pregnancy. 26264896 8 76 theme second 1309:1314 arg1 trimester 1316:1324 the second trimester 1305:1324 the second trimester 1305:1324 With some lectins, the intensity of binding diminished after the second trimester. 26264896 1 77 theme pregnancy 206:214 arg1 course 196:201 the course 192:201 the course of pregnancy 192:214 INTRODUCTION This study examines the glucose metabolism and glycosylation of villous macrophages (Hofbauer cells) over the course of pregnancy. 26264896 5 78 theme macrophage 965:974 arg1 types 956:960 other types 950:960 other types of macrophage 950:974 Glucose transporter-3 but not -1 was present in the cells as has been found in other types of macrophage. 26264896 7 79 theme small 1228:1232 arg1 granules 1234:1241 small granules 1228:1241 small granules 1228:1241 Glycan profiles were obtained for Hofbauer cell plasma membranes, cytosol, lysosomes and small granules. 26264896 10 80 theme commensurate 1435:1446 arg1 properties 1424:1433 properties 1424:1433 properties commensurate with their phagocytic activity with numerous lysosomal vacuoles and heavily glycosylated plasma membranes and granules, most evident in the first half of pregnancy 1424:1610 DISCUSSION Hofbauer cells have properties commensurate with their phagocytic activity with numerous lysosomal vacuoles and heavily glycosylated plasma membranes and granules, most evident in the first half of pregnancy. 26264896 4 81 theme phosphorylase 782:794 arg1 expression 796:805 glycogen phosphorylase expression 773:805 glycogen phosphorylase expression 773:805 RESULTS Little stored glycogen could be demonstrated by Bandeiraea simplicifolia-II agglutinin binding and, by immunocytochemistry, low levels of glycogen synthase were located within the cells, though glycogen phosphorylase expression, an enzyme releasing glucose from glycogen chains, was intense. 26264896 4 81 theme phosphorylase 782:794 arg1 enzyme 811:816 an enzyme 808:816 an enzyme releasing glucose from glycogen chains 808:855 RESULTS Little stored glycogen could be demonstrated by Bandeiraea simplicifolia-II agglutinin binding and, by immunocytochemistry, low levels of glycogen synthase were located within the cells, though glycogen phosphorylase expression, an enzyme releasing glucose from glycogen chains, was intense. 26264896 0 82 theme human 56:60 arg1 pregnancy 62:70 human pregnancy 56:70 human pregnancy 56:70 Functional changes in Hofbauer cell glycobiology during human pregnancy. 26264896 5 83 located present 908:914 arg1 cells 923:927 the cells 919:927 the cells 919:927 Glucose transporter-3 but not -1 was present in the cells as has been found in other types of macrophage. 26264896 5 83 located present 908:914 arg2 transporter-3 879:891 Glucose transporter-3 871:891 Glucose transporter-3 but not -1 871:902 Glucose transporter-3 but not -1 was present in the cells as has been found in other types of macrophage. 26264896 5 83 located present 908:914 arg2 -1 901:902 -1 901:902 -1 901:902 Glucose transporter-3 but not -1 was present in the cells as has been found in other types of macrophage. 26264896 10 84 theme numerous 1484:1491 arg1 vacuoles 1503:1510 numerous lysosomal vacuoles 1484:1510 numerous lysosomal vacuoles 1484:1510 DISCUSSION Hofbauer cells have properties commensurate with their phagocytic activity with numerous lysosomal vacuoles and heavily glycosylated plasma membranes and granules, most evident in the first half of pregnancy. 26264896 6 85 dep cells 1054:1058 arg1 both 1061:1064 both 1061:1064 both 1061:1064 Lectin histochemistry showed that many classes of glycan were present in the cells, both N and O-linked, though simple fucose residues could not be demonstrated. 26264896 6 85 dep cells 1054:1058 arg1 O-linked 1072:1079 O-linked 1072:1079 O-linked 1072:1079 Lectin histochemistry showed that many classes of glycan were present in the cells, both N and O-linked, though simple fucose residues could not be demonstrated. 26264896 2 86 theme glycogen 325:332 arg1 synthase 334:341 glycogen synthase 325:341 glycogen synthase 325:341 MATERIALS AND METHODS Sections of placentae from 6 weeks to term were stained with antibodies to α-amylase, glycogen synthase, glycogen phosphorylase and glucose transporters 1 and 3 (GLUT-1 and GLUT-3) while a panel of 24 lectins was applied to resin sections from 4 weeks onwards. 26264896 2 86 theme glycogen 325:332 arg1 antibodies 300:309 antibodies 300:309 antibodies to α-amylase 300:322 MATERIALS AND METHODS Sections of placentae from 6 weeks to term were stained with antibodies to α-amylase, glycogen synthase, glycogen phosphorylase and glucose transporters 1 and 3 (GLUT-1 and GLUT-3) while a panel of 24 lectins was applied to resin sections from 4 weeks onwards. 26264896 6 87 dep both 1061:1064 arg1 N 1066:1066 N 1066:1066 N 1066:1066 Lectin histochemistry showed that many classes of glycan were present in the cells, both N and O-linked, though simple fucose residues could not be demonstrated. 26264896 5 88 from present 908:914 arg1 cells 923:927 the cells 919:927 the cells 919:927 Glucose transporter-3 but not -1 was present in the cells as has been found in other types of macrophage. 26264896 9 89 theme Morphological 1327:1339 arg1 changes 1341:1347 Morphological changes 1327:1347 Morphological changes 1327:1347 Morphological changes also occurred over the course of pregnancy. 26264896 4 90 theme Little 579:584 arg1 glycogen 593:600 RESULTS Little stored glycogen 571:600 RESULTS Little stored glycogen 571:600 RESULTS Little stored glycogen could be demonstrated by Bandeiraea simplicifolia-II agglutinin binding and, by immunocytochemistry, low levels of glycogen synthase were located within the cells, though glycogen phosphorylase expression, an enzyme releasing glucose from glycogen chains, was intense. 25677974 0 0 theme lipopolysaccharide 98:115 arg1 endotoxicity 82:93 the endotoxicity 78:93 the endotoxicity of lipopolysaccharide 78:115 Heterologous expression of 3-O-deacylase in Acinetobacter baumannii modulates the endotoxicity of lipopolysaccharide. 25677974 4 1 theme decreased 747:755 arg1 ability 757:763 a statistically significant decreased ability 719:763 a statistically significant decreased ability to produce IL-6 719:779 Compared with wild-type LPS, outer membrane vesicles and inactivated whole cells of engineered bacteria had a statistically significant decreased ability to produce IL-6. 25677974 5 2 theme negative-ion 816:827 arg1 spectrometry 892:903 negative-ion matrix-assisted laser desorption/ionization time-of-flight mass spectrometry 816:903 negative-ion matrix-assisted laser desorption/ionization time-of-flight mass spectrometry 816:903 Structural analysis of lipid A by negative-ion matrix-assisted laser desorption/ionization time-of-flight mass spectrometry revealed that the profile of lipid A fractions under PagL expression was changed. 25677974 0 3 from expression 13:22 arg1 baumannii 58:66 Acinetobacter baumannii 44:66 Acinetobacter baumannii 44:66 Heterologous expression of 3-O-deacylase in Acinetobacter baumannii modulates the endotoxicity of lipopolysaccharide. 25677974 6 4 theme IL-6 1189:1192 arg1 production 1194:1203 IL-6 production 1189:1203 IL-6 production 1189:1203 Taken together, our data showed that recombinant penta-acylated lipid A had less immunoreactivity and that the tetra-acylated version of lipid A with TLR4 antagonist activity decreased the induction of IL-6 production in the murine macrophage cell line J774 A.1. 25677974 1 5 theme potent 179:184 arg1 stimulator 186:195 a potent stimulator 177:195 a potent stimulator of proinflammatory cytokines, such as interleukin-6 (IL-6) 177:254 The lipopolysaccharide (LPS) of Acinetobacter baumannii is a potent stimulator of proinflammatory cytokines, such as interleukin-6 (IL-6). 25677974 1 5 theme potent 179:184 arg1 lipopolysaccharide 122:139 The lipopolysaccharide 118:139 The lipopolysaccharide (LPS) of Acinetobacter baumannii 118:172 The lipopolysaccharide (LPS) of Acinetobacter baumannii is a potent stimulator of proinflammatory cytokines, such as interleukin-6 (IL-6). 25677974 3 6 theme DNA 547:549 arg1 technology 551:560 recombinant DNA technology 535:560 recombinant DNA technology 535:560 The plasmid pMMB66EH-PagL obtained by recombinant DNA technology was electroporated into A. baumannii ATCC 19606. 25677974 6 7 theme cell 1230:1233 arg1 J774 1240:1243 the murine macrophage cell line J774 1208:1243 the murine macrophage cell line J774 A.1 1208:1247 Taken together, our data showed that recombinant penta-acylated lipid A had less immunoreactivity and that the tetra-acylated version of lipid A with TLR4 antagonist activity decreased the induction of IL-6 production in the murine macrophage cell line J774 A.1. 25677974 5 8 theme Structural 782:791 arg1 analysis 793:800 Structural analysis 782:800 Structural analysis of lipid A by negative-ion matrix-assisted laser desorption/ionization time-of-flight mass spectrometry 782:903 Structural analysis of lipid A by negative-ion matrix-assisted laser desorption/ionization time-of-flight mass spectrometry revealed that the profile of lipid A fractions under PagL expression was changed. 25677974 6 9 theme less 1063:1066 arg1 immunoreactivity 1068:1083 less immunoreactivity 1063:1083 less immunoreactivity 1063:1083 Taken together, our data showed that recombinant penta-acylated lipid A had less immunoreactivity and that the tetra-acylated version of lipid A with TLR4 antagonist activity decreased the induction of IL-6 production in the murine macrophage cell line J774 A.1. 25677974 3 10 theme A. 586:587 arg1 ATCC 599:602 A. baumannii ATCC 19606 586:608 A. baumannii ATCC 19606 586:608 The plasmid pMMB66EH-PagL obtained by recombinant DNA technology was electroporated into A. baumannii ATCC 19606. 25677974 3 11 theme plasmid 501:507 arg1 pMMB66EH-PagL 509:521 The plasmid pMMB66EH-PagL 497:521 The plasmid pMMB66EH-PagL obtained by recombinant DNA technology 497:560 The plasmid pMMB66EH-PagL obtained by recombinant DNA technology was electroporated into A. baumannii ATCC 19606. 25677974 4 12 theme significant 735:745 arg1 ability 757:763 a statistically significant decreased ability 719:763 a statistically significant decreased ability to produce IL-6 719:779 Compared with wild-type LPS, outer membrane vesicles and inactivated whole cells of engineered bacteria had a statistically significant decreased ability to produce IL-6. 25677974 6 13 theme macrophage 1219:1228 arg1 J774 1240:1243 the murine macrophage cell line J774 1208:1243 the murine macrophage cell line J774 A.1 1208:1247 Taken together, our data showed that recombinant penta-acylated lipid A had less immunoreactivity and that the tetra-acylated version of lipid A with TLR4 antagonist activity decreased the induction of IL-6 production in the murine macrophage cell line J774 A.1. 25677974 2 14 theme new 418:420 arg1 compound 434:441 a new therapeutic compound 416:441 a new therapeutic compound that could reduce detrimental inflammatory responses 416:494 The 3-O-deacylase (PagL)-modifying enzyme that removes the 3-O-linked acyl chain from the disaccharide backbone of lipid A provides the opportunity to develop a new therapeutic compound that could reduce detrimental inflammatory responses. 25677974 2 15 theme -modifying 281:290 arg1 enzyme 292:297 The 3-O-deacylase (PagL)-modifying enzyme 257:297 The 3-O-deacylase (PagL)-modifying enzyme that removes the 3-O-linked acyl chain from the disaccharide backbone of lipid A 257:378 The 3-O-deacylase (PagL)-modifying enzyme that removes the 3-O-linked acyl chain from the disaccharide backbone of lipid A provides the opportunity to develop a new therapeutic compound that could reduce detrimental inflammatory responses. 25677974 4 16 theme engineered 695:704 arg1 bacteria 706:713 engineered bacteria 695:713 engineered bacteria 695:713 Compared with wild-type LPS, outer membrane vesicles and inactivated whole cells of engineered bacteria had a statistically significant decreased ability to produce IL-6. 25677974 4 17 theme wild-type 625:633 arg1 LPS 635:637 wild-type LPS 625:637 wild-type LPS 625:637 Compared with wild-type LPS, outer membrane vesicles and inactivated whole cells of engineered bacteria had a statistically significant decreased ability to produce IL-6. 25677974 5 18 theme matrix-assisted 829:843 arg1 spectrometry 892:903 negative-ion matrix-assisted laser desorption/ionization time-of-flight mass spectrometry 816:903 negative-ion matrix-assisted laser desorption/ionization time-of-flight mass spectrometry 816:903 Structural analysis of lipid A by negative-ion matrix-assisted laser desorption/ionization time-of-flight mass spectrometry revealed that the profile of lipid A fractions under PagL expression was changed. 25677974 6 19 theme line 1235:1238 arg1 J774 1240:1243 the murine macrophage cell line J774 1208:1243 the murine macrophage cell line J774 A.1 1208:1247 Taken together, our data showed that recombinant penta-acylated lipid A had less immunoreactivity and that the tetra-acylated version of lipid A with TLR4 antagonist activity decreased the induction of IL-6 production in the murine macrophage cell line J774 A.1. 25677974 5 20 theme fractions 942:950 arg1 profile 923:929 the profile 919:929 the profile of lipid A fractions under PagL expression 919:972 Structural analysis of lipid A by negative-ion matrix-assisted laser desorption/ionization time-of-flight mass spectrometry revealed that the profile of lipid A fractions under PagL expression was changed. 25677974 5 21 theme mass 887:890 arg1 spectrometry 892:903 negative-ion matrix-assisted laser desorption/ionization time-of-flight mass spectrometry 816:903 negative-ion matrix-assisted laser desorption/ionization time-of-flight mass spectrometry 816:903 Structural analysis of lipid A by negative-ion matrix-assisted laser desorption/ionization time-of-flight mass spectrometry revealed that the profile of lipid A fractions under PagL expression was changed. 25677974 6 22 theme lipid 1124:1128 arg1 A 1130:1130 lipid A 1124:1130 lipid A 1124:1130 Taken together, our data showed that recombinant penta-acylated lipid A had less immunoreactivity and that the tetra-acylated version of lipid A with TLR4 antagonist activity decreased the induction of IL-6 production in the murine macrophage cell line J774 A.1. 25677974 2 23 from backbone 360:367 arg1 chain 332:336 the 3-O-linked acyl chain 312:336 the 3-O-linked acyl chain from the disaccharide backbone of lipid A 312:378 The 3-O-deacylase (PagL)-modifying enzyme that removes the 3-O-linked acyl chain from the disaccharide backbone of lipid A provides the opportunity to develop a new therapeutic compound that could reduce detrimental inflammatory responses. 25677974 2 24 theme acyl 327:330 arg1 chain 332:336 the 3-O-linked acyl chain 312:336 the 3-O-linked acyl chain from the disaccharide backbone of lipid A 312:378 The 3-O-deacylase (PagL)-modifying enzyme that removes the 3-O-linked acyl chain from the disaccharide backbone of lipid A provides the opportunity to develop a new therapeutic compound that could reduce detrimental inflammatory responses. 25677974 1 25 theme proinflammatory 200:214 arg1 cytokines 216:224 proinflammatory cytokines 200:224 proinflammatory cytokines 200:224 The lipopolysaccharide (LPS) of Acinetobacter baumannii is a potent stimulator of proinflammatory cytokines, such as interleukin-6 (IL-6). 25677974 1 25 theme proinflammatory 200:214 arg1 interleukin-6 235:247 interleukin-6 235:247 interleukin-6 (IL-6) 235:254 The lipopolysaccharide (LPS) of Acinetobacter baumannii is a potent stimulator of proinflammatory cytokines, such as interleukin-6 (IL-6). 25677974 0 26 theme Heterologous 0:11 arg1 expression 13:22 Heterologous expression 0:22 Heterologous expression of 3-O-deacylase in Acinetobacter baumannii 0:66 Heterologous expression of 3-O-deacylase in Acinetobacter baumannii modulates the endotoxicity of lipopolysaccharide. 25677974 6 27 from induction 1176:1184 arg1 A.1 1245:1247 the murine macrophage cell line J774 A.1 1208:1247 the murine macrophage cell line J774 A.1 1208:1247 Taken together, our data showed that recombinant penta-acylated lipid A had less immunoreactivity and that the tetra-acylated version of lipid A with TLR4 antagonist activity decreased the induction of IL-6 production in the murine macrophage cell line J774 A.1. 25677974 2 28 theme 3-O-linked 316:325 arg1 chain 332:336 the 3-O-linked acyl chain 312:336 the 3-O-linked acyl chain from the disaccharide backbone of lipid A 312:378 The 3-O-deacylase (PagL)-modifying enzyme that removes the 3-O-linked acyl chain from the disaccharide backbone of lipid A provides the opportunity to develop a new therapeutic compound that could reduce detrimental inflammatory responses. 25677974 1 29 theme cytokines 216:224 arg1 stimulator 186:195 a potent stimulator 177:195 a potent stimulator of proinflammatory cytokines, such as interleukin-6 (IL-6) 177:254 The lipopolysaccharide (LPS) of Acinetobacter baumannii is a potent stimulator of proinflammatory cytokines, such as interleukin-6 (IL-6). 25677974 1 29 theme cytokines 216:224 arg1 lipopolysaccharide 122:139 The lipopolysaccharide 118:139 The lipopolysaccharide (LPS) of Acinetobacter baumannii 118:172 The lipopolysaccharide (LPS) of Acinetobacter baumannii is a potent stimulator of proinflammatory cytokines, such as interleukin-6 (IL-6). 25677974 0 30 theme 3-O-deacylase 27:39 arg1 expression 13:22 Heterologous expression 0:22 Heterologous expression of 3-O-deacylase in Acinetobacter baumannii 0:66 Heterologous expression of 3-O-deacylase in Acinetobacter baumannii modulates the endotoxicity of lipopolysaccharide. 25677974 6 31 with version 1113:1119 arg1 activity 1153:1160 TLR4 antagonist activity 1137:1160 TLR4 antagonist activity 1137:1160 Taken together, our data showed that recombinant penta-acylated lipid A had less immunoreactivity and that the tetra-acylated version of lipid A with TLR4 antagonist activity decreased the induction of IL-6 production in the murine macrophage cell line J774 A.1. 25677974 3 32 theme baumannii 589:597 arg1 ATCC 599:602 A. baumannii ATCC 19606 586:608 A. baumannii ATCC 19606 586:608 The plasmid pMMB66EH-PagL obtained by recombinant DNA technology was electroporated into A. baumannii ATCC 19606. 25677974 2 33 theme therapeutic 422:432 arg1 compound 434:441 a new therapeutic compound 416:441 a new therapeutic compound that could reduce detrimental inflammatory responses 416:494 The 3-O-deacylase (PagL)-modifying enzyme that removes the 3-O-linked acyl chain from the disaccharide backbone of lipid A provides the opportunity to develop a new therapeutic compound that could reduce detrimental inflammatory responses. 25677974 6 34 theme J774 1240:1243 arg1 A.1 1245:1247 the murine macrophage cell line J774 A.1 1208:1247 the murine macrophage cell line J774 A.1 1208:1247 Taken together, our data showed that recombinant penta-acylated lipid A had less immunoreactivity and that the tetra-acylated version of lipid A with TLR4 antagonist activity decreased the induction of IL-6 production in the murine macrophage cell line J774 A.1. 25677974 6 35 theme lipid 1051:1055 arg1 A 1057:1057 recombinant penta-acylated lipid A 1024:1057 recombinant penta-acylated lipid A 1024:1057 Taken together, our data showed that recombinant penta-acylated lipid A had less immunoreactivity and that the tetra-acylated version of lipid A with TLR4 antagonist activity decreased the induction of IL-6 production in the murine macrophage cell line J774 A.1. 25677974 3 36 theme recombinant 535:545 arg1 technology 551:560 recombinant DNA technology 535:560 recombinant DNA technology 535:560 The plasmid pMMB66EH-PagL obtained by recombinant DNA technology was electroporated into A. baumannii ATCC 19606. 25677974 1 37 theme baumannii 164:172 arg1 LPS 142:144 LPS 142:144 LPS 142:144 The lipopolysaccharide (LPS) of Acinetobacter baumannii is a potent stimulator of proinflammatory cytokines, such as interleukin-6 (IL-6). 25677974 1 37 theme baumannii 164:172 arg1 lipopolysaccharide 122:139 The lipopolysaccharide 118:139 The lipopolysaccharide (LPS) of Acinetobacter baumannii 118:172 The lipopolysaccharide (LPS) of Acinetobacter baumannii is a potent stimulator of proinflammatory cytokines, such as interleukin-6 (IL-6). 25677974 1 37 theme baumannii 164:172 arg1 stimulator 186:195 a potent stimulator 177:195 a potent stimulator of proinflammatory cytokines, such as interleukin-6 (IL-6) 177:254 The lipopolysaccharide (LPS) of Acinetobacter baumannii is a potent stimulator of proinflammatory cytokines, such as interleukin-6 (IL-6). 25677974 0 38 theme Acinetobacter 44:56 arg1 baumannii 58:66 Acinetobacter baumannii 44:66 Acinetobacter baumannii 44:66 Heterologous expression of 3-O-deacylase in Acinetobacter baumannii modulates the endotoxicity of lipopolysaccharide. 25677974 6 39 theme penta-acylated 1036:1049 arg1 A 1057:1057 recombinant penta-acylated lipid A 1024:1057 recombinant penta-acylated lipid A 1024:1057 Taken together, our data showed that recombinant penta-acylated lipid A had less immunoreactivity and that the tetra-acylated version of lipid A with TLR4 antagonist activity decreased the induction of IL-6 production in the murine macrophage cell line J774 A.1. 25677974 4 40 theme bacteria 706:713 arg1 cells 686:690 inactivated whole cells 668:690 inactivated whole cells 668:690 Compared with wild-type LPS, outer membrane vesicles and inactivated whole cells of engineered bacteria had a statistically significant decreased ability to produce IL-6. 25677974 4 40 theme bacteria 706:713 arg1 vesicles 655:662 outer membrane vesicles 640:662 outer membrane vesicles 640:662 Compared with wild-type LPS, outer membrane vesicles and inactivated whole cells of engineered bacteria had a statistically significant decreased ability to produce IL-6. 25677974 6 41 theme A 1130:1130 arg1 version 1113:1119 the tetra-acylated version 1094:1119 the tetra-acylated version of lipid A with TLR4 antagonist activity 1094:1160 Taken together, our data showed that recombinant penta-acylated lipid A had less immunoreactivity and that the tetra-acylated version of lipid A with TLR4 antagonist activity decreased the induction of IL-6 production in the murine macrophage cell line J774 A.1. 25677974 5 42 theme A 940:940 arg1 fractions 942:950 lipid A fractions 934:950 lipid A fractions 934:950 Structural analysis of lipid A by negative-ion matrix-assisted laser desorption/ionization time-of-flight mass spectrometry revealed that the profile of lipid A fractions under PagL expression was changed. 25677974 6 43 theme recombinant 1024:1034 arg1 A 1057:1057 recombinant penta-acylated lipid A 1024:1057 recombinant penta-acylated lipid A 1024:1057 Taken together, our data showed that recombinant penta-acylated lipid A had less immunoreactivity and that the tetra-acylated version of lipid A with TLR4 antagonist activity decreased the induction of IL-6 production in the murine macrophage cell line J774 A.1. 25677974 5 44 theme laser 845:849 arg1 spectrometry 892:903 negative-ion matrix-assisted laser desorption/ionization time-of-flight mass spectrometry 816:903 negative-ion matrix-assisted laser desorption/ionization time-of-flight mass spectrometry 816:903 Structural analysis of lipid A by negative-ion matrix-assisted laser desorption/ionization time-of-flight mass spectrometry revealed that the profile of lipid A fractions under PagL expression was changed. 25677974 4 45 theme whole 680:684 arg1 cells 686:690 inactivated whole cells 668:690 inactivated whole cells 668:690 Compared with wild-type LPS, outer membrane vesicles and inactivated whole cells of engineered bacteria had a statistically significant decreased ability to produce IL-6. 25677974 2 46 theme inflammatory 473:484 arg1 responses 486:494 detrimental inflammatory responses 461:494 detrimental inflammatory responses 461:494 The 3-O-deacylase (PagL)-modifying enzyme that removes the 3-O-linked acyl chain from the disaccharide backbone of lipid A provides the opportunity to develop a new therapeutic compound that could reduce detrimental inflammatory responses. 25677974 5 47 theme time-of-flight 873:885 arg1 spectrometry 892:903 negative-ion matrix-assisted laser desorption/ionization time-of-flight mass spectrometry 816:903 negative-ion matrix-assisted laser desorption/ionization time-of-flight mass spectrometry 816:903 Structural analysis of lipid A by negative-ion matrix-assisted laser desorption/ionization time-of-flight mass spectrometry revealed that the profile of lipid A fractions under PagL expression was changed. 25677974 5 48 theme A 811:811 arg1 analysis 793:800 Structural analysis 782:800 Structural analysis of lipid A by negative-ion matrix-assisted laser desorption/ionization time-of-flight mass spectrometry 782:903 Structural analysis of lipid A by negative-ion matrix-assisted laser desorption/ionization time-of-flight mass spectrometry revealed that the profile of lipid A fractions under PagL expression was changed. 25677974 6 49 theme production 1194:1203 arg1 induction 1176:1184 the induction 1172:1184 the induction of IL-6 production in the murine macrophage cell line J774 A.1 1172:1247 Taken together, our data showed that recombinant penta-acylated lipid A had less immunoreactivity and that the tetra-acylated version of lipid A with TLR4 antagonist activity decreased the induction of IL-6 production in the murine macrophage cell line J774 A.1. 25677974 2 50 theme disaccharide 347:358 arg1 backbone 360:367 the disaccharide backbone 343:367 the disaccharide backbone of lipid A 343:378 The 3-O-deacylase (PagL)-modifying enzyme that removes the 3-O-linked acyl chain from the disaccharide backbone of lipid A provides the opportunity to develop a new therapeutic compound that could reduce detrimental inflammatory responses. 25677974 2 51 theme detrimental 461:471 arg1 responses 486:494 detrimental inflammatory responses 461:494 detrimental inflammatory responses 461:494 The 3-O-deacylase (PagL)-modifying enzyme that removes the 3-O-linked acyl chain from the disaccharide backbone of lipid A provides the opportunity to develop a new therapeutic compound that could reduce detrimental inflammatory responses. 25677974 6 52 theme antagonist 1142:1151 arg1 activity 1153:1160 TLR4 antagonist activity 1137:1160 TLR4 antagonist activity 1137:1160 Taken together, our data showed that recombinant penta-acylated lipid A had less immunoreactivity and that the tetra-acylated version of lipid A with TLR4 antagonist activity decreased the induction of IL-6 production in the murine macrophage cell line J774 A.1. 25677974 6 53 contain had 1059:1061 arg1 A 1057:1057 recombinant penta-acylated lipid A 1024:1057 recombinant penta-acylated lipid A 1024:1057 Taken together, our data showed that recombinant penta-acylated lipid A had less immunoreactivity and that the tetra-acylated version of lipid A with TLR4 antagonist activity decreased the induction of IL-6 production in the murine macrophage cell line J774 A.1. 25677974 6 53 contain had 1059:1061 arg2 immunoreactivity 1068:1083 less immunoreactivity 1063:1083 less immunoreactivity 1063:1083 Taken together, our data showed that recombinant penta-acylated lipid A had less immunoreactivity and that the tetra-acylated version of lipid A with TLR4 antagonist activity decreased the induction of IL-6 production in the murine macrophage cell line J774 A.1. 25677974 6 54 theme murine 1212:1217 arg1 J774 1240:1243 the murine macrophage cell line J774 1208:1243 the murine macrophage cell line J774 A.1 1208:1247 Taken together, our data showed that recombinant penta-acylated lipid A had less immunoreactivity and that the tetra-acylated version of lipid A with TLR4 antagonist activity decreased the induction of IL-6 production in the murine macrophage cell line J774 A.1. 25677974 2 55 link 3-O-linked 316:325 arg1 chain 332:336 the 3-O-linked acyl chain 312:336 the 3-O-linked acyl chain from the disaccharide backbone of lipid A 312:378 The 3-O-deacylase (PagL)-modifying enzyme that removes the 3-O-linked acyl chain from the disaccharide backbone of lipid A provides the opportunity to develop a new therapeutic compound that could reduce detrimental inflammatory responses. 25677974 4 56 contain had 715:717 arg1 cells 686:690 inactivated whole cells 668:690 inactivated whole cells 668:690 Compared with wild-type LPS, outer membrane vesicles and inactivated whole cells of engineered bacteria had a statistically significant decreased ability to produce IL-6. 25677974 4 56 contain had 715:717 arg2 ability 757:763 a statistically significant decreased ability 719:763 a statistically significant decreased ability to produce IL-6 719:779 Compared with wild-type LPS, outer membrane vesicles and inactivated whole cells of engineered bacteria had a statistically significant decreased ability to produce IL-6. 25677974 4 56 contain had 715:717 arg1 vesicles 655:662 outer membrane vesicles 640:662 outer membrane vesicles 640:662 Compared with wild-type LPS, outer membrane vesicles and inactivated whole cells of engineered bacteria had a statistically significant decreased ability to produce IL-6. 25677974 5 57 theme PagL 958:961 arg1 expression 963:972 PagL expression 958:972 PagL expression 958:972 Structural analysis of lipid A by negative-ion matrix-assisted laser desorption/ionization time-of-flight mass spectrometry revealed that the profile of lipid A fractions under PagL expression was changed. 25677974 4 58 theme outer 640:644 arg1 vesicles 655:662 outer membrane vesicles 640:662 outer membrane vesicles 640:662 Compared with wild-type LPS, outer membrane vesicles and inactivated whole cells of engineered bacteria had a statistically significant decreased ability to produce IL-6. 25677974 6 59 theme TLR4 1137:1140 arg1 activity 1153:1160 TLR4 antagonist activity 1137:1160 TLR4 antagonist activity 1137:1160 Taken together, our data showed that recombinant penta-acylated lipid A had less immunoreactivity and that the tetra-acylated version of lipid A with TLR4 antagonist activity decreased the induction of IL-6 production in the murine macrophage cell line J774 A.1. 25677974 1 60 theme Acinetobacter 150:162 arg1 baumannii 164:172 Acinetobacter baumannii 150:172 Acinetobacter baumannii 150:172 The lipopolysaccharide (LPS) of Acinetobacter baumannii is a potent stimulator of proinflammatory cytokines, such as interleukin-6 (IL-6). 25677974 5 61 theme lipid 805:809 arg1 A 811:811 lipid A 805:811 lipid A 805:811 Structural analysis of lipid A by negative-ion matrix-assisted laser desorption/ionization time-of-flight mass spectrometry revealed that the profile of lipid A fractions under PagL expression was changed. 25677974 5 62 theme lipid 934:938 arg1 fractions 942:950 lipid A fractions 934:950 lipid A fractions 934:950 Structural analysis of lipid A by negative-ion matrix-assisted laser desorption/ionization time-of-flight mass spectrometry revealed that the profile of lipid A fractions under PagL expression was changed. 25677974 4 63 theme inactivated 668:678 arg1 cells 686:690 inactivated whole cells 668:690 inactivated whole cells 668:690 Compared with wild-type LPS, outer membrane vesicles and inactivated whole cells of engineered bacteria had a statistically significant decreased ability to produce IL-6. 25677974 2 64 theme A 378:378 arg1 backbone 360:367 the disaccharide backbone 343:367 the disaccharide backbone of lipid A 343:378 The 3-O-deacylase (PagL)-modifying enzyme that removes the 3-O-linked acyl chain from the disaccharide backbone of lipid A provides the opportunity to develop a new therapeutic compound that could reduce detrimental inflammatory responses. 25677974 6 65 theme tetra-acylated 1098:1111 arg1 version 1113:1119 the tetra-acylated version 1094:1119 the tetra-acylated version of lipid A with TLR4 antagonist activity 1094:1160 Taken together, our data showed that recombinant penta-acylated lipid A had less immunoreactivity and that the tetra-acylated version of lipid A with TLR4 antagonist activity decreased the induction of IL-6 production in the murine macrophage cell line J774 A.1. 25677974 5 66 theme desorption/ionization 851:871 arg1 spectrometry 892:903 negative-ion matrix-assisted laser desorption/ionization time-of-flight mass spectrometry 816:903 negative-ion matrix-assisted laser desorption/ionization time-of-flight mass spectrometry 816:903 Structural analysis of lipid A by negative-ion matrix-assisted laser desorption/ionization time-of-flight mass spectrometry revealed that the profile of lipid A fractions under PagL expression was changed. 25677974 2 67 theme lipid 372:376 arg1 A 378:378 lipid A 372:378 lipid A 372:378 The 3-O-deacylase (PagL)-modifying enzyme that removes the 3-O-linked acyl chain from the disaccharide backbone of lipid A provides the opportunity to develop a new therapeutic compound that could reduce detrimental inflammatory responses. 25677974 4 68 theme membrane 646:653 arg1 vesicles 655:662 outer membrane vesicles 640:662 outer membrane vesicles 640:662 Compared with wild-type LPS, outer membrane vesicles and inactivated whole cells of engineered bacteria had a statistically significant decreased ability to produce IL-6. 25447273 6 0 theme different 1276:1284 arg1 branches 1286:1293 different branches 1276:1293 different branches of the N-acetylgalactosaminyltransferase 1276:1334 In summary, these data demonstrate that these two enzymes from different branches of the N-acetylgalactosaminyltransferase do not only display differential substrate specificities, but also specific and distinct expression pattern and biological activities in vivo. 25447273 6 1 theme N-acetylgalactosaminyltransferase 1302:1334 arg1 branches 1286:1293 different branches 1276:1293 different branches of the N-acetylgalactosaminyltransferase 1276:1334 In summary, these data demonstrate that these two enzymes from different branches of the N-acetylgalactosaminyltransferase do not only display differential substrate specificities, but also specific and distinct expression pattern and biological activities in vivo. 25447273 0 2 theme contrasting 100:110 arg1 roles 112:116 contrasting roles 100:116 contrasting roles in embryogenesis 100:133 Biological and biochemical properties of two Xenopus laevis N-acetylgalactosaminyltransferases with contrasting roles in embryogenesis. 25447273 4 3 theme in 870:871 arg1 function 878:885 their in vivo function 864:885 their in vivo function during X. laevis embyrogenesis 864:916 In this study we have examined these two enzymes further and show differences in their in vivo function during X. laevis embyrogenesis as evidenced by in situ hybridization and overexpression experiments. 25447273 5 4 theme EA2 1069:1071 arg1 peptide 1073:1079 the EA2 peptide 1065:1079 the EA2 peptide 1065:1079 In terms of enzymatic activity, both enzymes were found to be active towards the EA2 peptide, but display differential activity towards a peptide based on the sequence of ActR-IIB, a receptor relevant to TGF-β/BMP signaling. 25447273 6 5 theme biological 1448:1457 arg1 activities 1459:1468 biological activities 1448:1468 biological activities in vivo 1448:1476 In summary, these data demonstrate that these two enzymes from different branches of the N-acetylgalactosaminyltransferase do not only display differential substrate specificities, but also specific and distinct expression pattern and biological activities in vivo. 25447273 4 6 dep in 934:935 arg1 situ 937:940 situ 937:940 situ 937:940 In this study we have examined these two enzymes further and show differences in their in vivo function during X. laevis embyrogenesis as evidenced by in situ hybridization and overexpression experiments. 25447273 4 7 dep in 870:871 arg1 vivo 873:876 vivo 873:876 vivo 873:876 In this study we have examined these two enzymes further and show differences in their in vivo function during X. laevis embyrogenesis as evidenced by in situ hybridization and overexpression experiments. 25447273 3 8 theme Xenopus 596:602 arg1 laevis 604:609 the African clawed frog (Xenopus laevis) 571:610 the African clawed frog (Xenopus laevis) 571:610 However, two N-acetylgalactosaminyltransferases (xGalNAc-T6 and xGalNAc-T16) from the African clawed frog (Xenopus laevis), which are most homologous to those encoded by the human GALNT6 and GALNT16 (GALNTL1) genes, were shown to have contrasting roles in TGF-β/BMP signaling in embryogenesis. 25447273 6 9 theme substrate 1369:1377 arg1 specificities 1379:1391 differential substrate specificities 1356:1391 differential substrate specificities 1356:1391 In summary, these data demonstrate that these two enzymes from different branches of the N-acetylgalactosaminyltransferase do not only display differential substrate specificities, but also specific and distinct expression pattern and biological activities in vivo. 25447273 5 10 theme differential 1094:1105 arg1 activity 1107:1114 differential activity 1094:1114 differential activity towards a peptide based on the sequence of ActR-IIB, a receptor relevant to TGF-β/BMP signaling 1094:1210 In terms of enzymatic activity, both enzymes were found to be active towards the EA2 peptide, but display differential activity towards a peptide based on the sequence of ActR-IIB, a receptor relevant to TGF-β/BMP signaling. 25447273 0 11 with N-acetylgalactosaminyltransferases 60:93 arg1 roles 112:116 contrasting roles 100:116 contrasting roles in embryogenesis 100:133 Biological and biochemical properties of two Xenopus laevis N-acetylgalactosaminyltransferases with contrasting roles in embryogenesis. 25447273 3 12 theme clawed 583:588 arg1 laevis 604:609 the African clawed frog (Xenopus laevis) 571:610 the African clawed frog (Xenopus laevis) 571:610 However, two N-acetylgalactosaminyltransferases (xGalNAc-T6 and xGalNAc-T16) from the African clawed frog (Xenopus laevis), which are most homologous to those encoded by the human GALNT6 and GALNT16 (GALNTL1) genes, were shown to have contrasting roles in TGF-β/BMP signaling in embryogenesis. 25447273 4 13 theme overexpression 960:973 arg1 experiments 975:985 overexpression experiments 960:985 overexpression experiments 960:985 In this study we have examined these two enzymes further and show differences in their in vivo function during X. laevis embyrogenesis as evidenced by in situ hybridization and overexpression experiments. 25447273 4 14 from differences 849:859 arg1 function 878:885 their in vivo function 864:885 their in vivo function during X. laevis embyrogenesis 864:916 In this study we have examined these two enzymes further and show differences in their in vivo function during X. laevis embyrogenesis as evidenced by in situ hybridization and overexpression experiments. 25447273 3 15 from signaling 755:763 arg1 embryogenesis 768:780 embryogenesis 768:780 embryogenesis 768:780 However, two N-acetylgalactosaminyltransferases (xGalNAc-T6 and xGalNAc-T16) from the African clawed frog (Xenopus laevis), which are most homologous to those encoded by the human GALNT6 and GALNT16 (GALNTL1) genes, were shown to have contrasting roles in TGF-β/BMP signaling in embryogenesis. 25447273 3 16 theme frog 590:593 arg1 laevis 604:609 the African clawed frog (Xenopus laevis) 571:610 the African clawed frog (Xenopus laevis) 571:610 However, two N-acetylgalactosaminyltransferases (xGalNAc-T6 and xGalNAc-T16) from the African clawed frog (Xenopus laevis), which are most homologous to those encoded by the human GALNT6 and GALNT16 (GALNTL1) genes, were shown to have contrasting roles in TGF-β/BMP signaling in embryogenesis. 25447273 3 17 theme contrasting 724:734 arg1 roles 736:740 contrasting roles 724:740 contrasting roles 724:740 However, two N-acetylgalactosaminyltransferases (xGalNAc-T6 and xGalNAc-T16) from the African clawed frog (Xenopus laevis), which are most homologous to those encoded by the human GALNT6 and GALNT16 (GALNTL1) genes, were shown to have contrasting roles in TGF-β/BMP signaling in embryogenesis. 25447273 4 18 theme X. 894:895 arg1 laevis 897:902 X. laevis 894:902 X. laevis embyrogenesis 894:916 In this study we have examined these two enzymes further and show differences in their in vivo function during X. laevis embyrogenesis as evidenced by in situ hybridization and overexpression experiments. 25447273 2 19 theme mammalian 422:430 arg1 forms 432:436 the mammalian forms 418:436 the mammalian forms of these enzymes 418:453 Until now, the mammalian forms of these enzymes have been the best characterized. 25447273 0 20 theme Biological 0:9 arg1 properties 27:36 Biological and biochemical properties 0:36 Biological and biochemical properties of two Xenopus laevis 0:58 Biological and biochemical properties of two Xenopus laevis N-acetylgalactosaminyltransferases with contrasting roles in embryogenesis. 25447273 1 21 theme important 313:321 arg1 roles 323:327 important roles 313:327 important roles 313:327 The biosynthesis of mucin-type O-linked glycans in animals is initiated by members of the large family of polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts), which play important roles in embryogenesis, organogenesis, adult tissue homeostasis and carcinogenesis. 25447273 1 22 from biosynthesis 140:151 arg1 animals 187:193 animals 187:193 animals 187:193 The biosynthesis of mucin-type O-linked glycans in animals is initiated by members of the large family of polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts), which play important roles in embryogenesis, organogenesis, adult tissue homeostasis and carcinogenesis. 25447273 3 23 theme GALNT16 680:686 arg1 genes 698:702 the human GALNT6 and GALNT16 (GALNTL1) genes 659:702 the human GALNT6 and GALNT16 (GALNTL1) genes 659:702 However, two N-acetylgalactosaminyltransferases (xGalNAc-T6 and xGalNAc-T16) from the African clawed frog (Xenopus laevis), which are most homologous to those encoded by the human GALNT6 and GALNT16 (GALNTL1) genes, were shown to have contrasting roles in TGF-β/BMP signaling in embryogenesis. 25447273 4 24 dep differences 849:859 arg1 evidenced 921:929 evidenced 921:929 evidenced by in situ hybridization and overexpression experiments 921:985 In this study we have examined these two enzymes further and show differences in their in vivo function during X. laevis embyrogenesis as evidenced by in situ hybridization and overexpression experiments. 25447273 6 25 theme differential 1356:1367 arg1 specificities 1379:1391 differential substrate specificities 1356:1391 differential substrate specificities 1356:1391 In summary, these data demonstrate that these two enzymes from different branches of the N-acetylgalactosaminyltransferase do not only display differential substrate specificities, but also specific and distinct expression pattern and biological activities in vivo. 25447273 0 26 theme biochemical 15:25 arg1 properties 27:36 Biological and biochemical properties 0:36 Biological and biochemical properties of two Xenopus laevis 0:58 Biological and biochemical properties of two Xenopus laevis N-acetylgalactosaminyltransferases with contrasting roles in embryogenesis. 25447273 3 27 theme TGF-β/BMP 745:753 arg1 signaling 755:763 TGF-β/BMP signaling 745:763 TGF-β/BMP signaling in embryogenesis 745:780 However, two N-acetylgalactosaminyltransferases (xGalNAc-T6 and xGalNAc-T16) from the African clawed frog (Xenopus laevis), which are most homologous to those encoded by the human GALNT6 and GALNT16 (GALNTL1) genes, were shown to have contrasting roles in TGF-β/BMP signaling in embryogenesis. 25447273 6 28 theme distinct 1416:1423 arg1 pattern 1436:1442 specific and distinct expression pattern 1403:1442 specific and distinct expression pattern 1403:1442 In summary, these data demonstrate that these two enzymes from different branches of the N-acetylgalactosaminyltransferase do not only display differential substrate specificities, but also specific and distinct expression pattern and biological activities in vivo. 25447273 0 29 from roles 112:116 arg1 embryogenesis 121:133 embryogenesis 121:133 embryogenesis 121:133 Biological and biochemical properties of two Xenopus laevis N-acetylgalactosaminyltransferases with contrasting roles in embryogenesis. 25447273 1 30 theme large 226:230 arg1 family 232:237 the large family 222:237 the large family of polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts) 222:299 The biosynthesis of mucin-type O-linked glycans in animals is initiated by members of the large family of polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts), which play important roles in embryogenesis, organogenesis, adult tissue homeostasis and carcinogenesis. 25447273 5 31 theme relevant 1180:1187 arg1 ActR-IIB 1159:1166 ActR-IIB 1159:1166 ActR-IIB 1159:1166 In terms of enzymatic activity, both enzymes were found to be active towards the EA2 peptide, but display differential activity towards a peptide based on the sequence of ActR-IIB, a receptor relevant to TGF-β/BMP signaling. 25447273 5 31 theme relevant 1180:1187 arg1 receptor 1171:1178 a receptor 1169:1178 a receptor relevant to TGF-β/BMP signaling 1169:1210 In terms of enzymatic activity, both enzymes were found to be active towards the EA2 peptide, but display differential activity towards a peptide based on the sequence of ActR-IIB, a receptor relevant to TGF-β/BMP signaling. 25447273 5 32 theme TGF-β/BMP 1192:1200 arg1 signaling 1202:1210 TGF-β/BMP signaling 1192:1210 TGF-β/BMP signaling 1192:1210 In terms of enzymatic activity, both enzymes were found to be active towards the EA2 peptide, but display differential activity towards a peptide based on the sequence of ActR-IIB, a receptor relevant to TGF-β/BMP signaling. 25447273 1 33 theme family 232:237 arg1 members 211:217 members 211:217 members 211:217 The biosynthesis of mucin-type O-linked glycans in animals is initiated by members of the large family of polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts), which play important roles in embryogenesis, organogenesis, adult tissue homeostasis and carcinogenesis. 25447273 2 34 theme enzymes 447:453 arg1 forms 432:436 the mammalian forms 418:436 the mammalian forms of these enzymes 418:453 Until now, the mammalian forms of these enzymes have been the best characterized. 25447273 6 35 theme specific 1403:1410 arg1 pattern 1436:1442 specific and distinct expression pattern 1403:1442 specific and distinct expression pattern 1403:1442 In summary, these data demonstrate that these two enzymes from different branches of the N-acetylgalactosaminyltransferase do not only display differential substrate specificities, but also specific and distinct expression pattern and biological activities in vivo. 25447273 4 36 theme in 934:935 arg1 hybridization 942:954 in situ hybridization 934:954 in situ hybridization 934:954 In this study we have examined these two enzymes further and show differences in their in vivo function during X. laevis embyrogenesis as evidenced by in situ hybridization and overexpression experiments. 25447273 3 37 theme human 663:667 arg1 GALNT6 669:674 human GALNT6 663:674 human GALNT6 663:674 However, two N-acetylgalactosaminyltransferases (xGalNAc-T6 and xGalNAc-T16) from the African clawed frog (Xenopus laevis), which are most homologous to those encoded by the human GALNT6 and GALNT16 (GALNTL1) genes, were shown to have contrasting roles in TGF-β/BMP signaling in embryogenesis. 25447273 5 38 theme ActR-IIB 1159:1166 arg1 sequence 1147:1154 the sequence 1143:1154 the sequence of ActR-IIB, a receptor relevant to TGF-β/BMP signaling 1143:1210 In terms of enzymatic activity, both enzymes were found to be active towards the EA2 peptide, but display differential activity towards a peptide based on the sequence of ActR-IIB, a receptor relevant to TGF-β/BMP signaling. 25447273 0 39 theme laevis 53:58 arg1 properties 27:36 Biological and biochemical properties 0:36 Biological and biochemical properties of two Xenopus laevis 0:58 Biological and biochemical properties of two Xenopus laevis N-acetylgalactosaminyltransferases with contrasting roles in embryogenesis. 25447273 6 40 from branches 1286:1293 arg1 enzymes 1263:1269 these two enzymes 1253:1269 these two enzymes from different branches of the N-acetylgalactosaminyltransferase 1253:1334 In summary, these data demonstrate that these two enzymes from different branches of the N-acetylgalactosaminyltransferase do not only display differential substrate specificities, but also specific and distinct expression pattern and biological activities in vivo. 25447273 4 41 theme laevis 897:902 arg1 embyrogenesis 904:916 X. laevis embyrogenesis 894:916 X. laevis embyrogenesis 894:916 In this study we have examined these two enzymes further and show differences in their in vivo function during X. laevis embyrogenesis as evidenced by in situ hybridization and overexpression experiments. 25447273 3 42 theme GALNT6 669:674 arg1 genes 698:702 the human GALNT6 and GALNT16 (GALNTL1) genes 659:702 the human GALNT6 and GALNT16 (GALNTL1) genes 659:702 However, two N-acetylgalactosaminyltransferases (xGalNAc-T6 and xGalNAc-T16) from the African clawed frog (Xenopus laevis), which are most homologous to those encoded by the human GALNT6 and GALNT16 (GALNTL1) genes, were shown to have contrasting roles in TGF-β/BMP signaling in embryogenesis. 25447273 0 43 theme Xenopus 45:51 arg1 laevis 53:58 two Xenopus laevis 41:58 two Xenopus laevis 41:58 Biological and biochemical properties of two Xenopus laevis N-acetylgalactosaminyltransferases with contrasting roles in embryogenesis. 25447273 1 44 link O-linked 167:174 arg1 glycans 176:182 mucin-type O-linked glycans 156:182 mucin-type O-linked glycans 156:182 The biosynthesis of mucin-type O-linked glycans in animals is initiated by members of the large family of polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts), which play important roles in embryogenesis, organogenesis, adult tissue homeostasis and carcinogenesis. 25447273 3 45 contain have 719:722 arg2 roles 736:740 contrasting roles 724:740 contrasting roles 724:740 However, two N-acetylgalactosaminyltransferases (xGalNAc-T6 and xGalNAc-T16) from the African clawed frog (Xenopus laevis), which are most homologous to those encoded by the human GALNT6 and GALNT16 (GALNTL1) genes, were shown to have contrasting roles in TGF-β/BMP signaling in embryogenesis. 25447273 3 45 contain have 719:722 arg1 N-acetylgalactosaminyltransferases 502:535 two N-acetylgalactosaminyltransferases 498:535 two N-acetylgalactosaminyltransferases (xGalNAc-T6 and xGalNAc-T16) 498:564 However, two N-acetylgalactosaminyltransferases (xGalNAc-T6 and xGalNAc-T16) from the African clawed frog (Xenopus laevis), which are most homologous to those encoded by the human GALNT6 and GALNT16 (GALNTL1) genes, were shown to have contrasting roles in TGF-β/BMP signaling in embryogenesis. 25447273 3 46 from laevis 604:609 arg1 N-acetylgalactosaminyltransferases 502:535 two N-acetylgalactosaminyltransferases 498:535 two N-acetylgalactosaminyltransferases (xGalNAc-T6 and xGalNAc-T16) 498:564 However, two N-acetylgalactosaminyltransferases (xGalNAc-T6 and xGalNAc-T16) from the African clawed frog (Xenopus laevis), which are most homologous to those encoded by the human GALNT6 and GALNT16 (GALNTL1) genes, were shown to have contrasting roles in TGF-β/BMP signaling in embryogenesis. 25447273 1 47 theme adult 362:366 arg1 homeostasis 375:385 adult tissue homeostasis 362:385 adult tissue homeostasis 362:385 The biosynthesis of mucin-type O-linked glycans in animals is initiated by members of the large family of polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts), which play important roles in embryogenesis, organogenesis, adult tissue homeostasis and carcinogenesis. 25447273 5 48 theme enzymatic 1000:1008 arg1 activity 1010:1017 enzymatic activity 1000:1017 enzymatic activity 1000:1017 In terms of enzymatic activity, both enzymes were found to be active towards the EA2 peptide, but display differential activity towards a peptide based on the sequence of ActR-IIB, a receptor relevant to TGF-β/BMP signaling. 25447273 1 49 theme mucin-type 156:165 arg1 glycans 176:182 mucin-type O-linked glycans 156:182 mucin-type O-linked glycans 156:182 The biosynthesis of mucin-type O-linked glycans in animals is initiated by members of the large family of polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts), which play important roles in embryogenesis, organogenesis, adult tissue homeostasis and carcinogenesis. 25447273 1 50 theme polypeptide 242:252 arg1 GalNAc-Ts 290:298 GalNAc-Ts 290:298 GalNAc-Ts 290:298 The biosynthesis of mucin-type O-linked glycans in animals is initiated by members of the large family of polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts), which play important roles in embryogenesis, organogenesis, adult tissue homeostasis and carcinogenesis. 25447273 1 50 theme polypeptide 242:252 arg1 N-acetylgalactosaminyltransferases 254:287 polypeptide N-acetylgalactosaminyltransferases 242:287 polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts) 242:299 The biosynthesis of mucin-type O-linked glycans in animals is initiated by members of the large family of polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts), which play important roles in embryogenesis, organogenesis, adult tissue homeostasis and carcinogenesis. 25447273 5 51 theme activity 1010:1017 arg1 terms 991:995 terms 991:995 terms of enzymatic activity 991:1017 In terms of enzymatic activity, both enzymes were found to be active towards the EA2 peptide, but display differential activity towards a peptide based on the sequence of ActR-IIB, a receptor relevant to TGF-β/BMP signaling. 25447273 1 52 theme O-linked 167:174 arg1 glycans 176:182 mucin-type O-linked glycans 156:182 mucin-type O-linked glycans 156:182 The biosynthesis of mucin-type O-linked glycans in animals is initiated by members of the large family of polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts), which play important roles in embryogenesis, organogenesis, adult tissue homeostasis and carcinogenesis. 25447273 1 53 theme N-acetylgalactosaminyltransferases 254:287 arg1 family 232:237 the large family 222:237 the large family of polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts) 222:299 The biosynthesis of mucin-type O-linked glycans in animals is initiated by members of the large family of polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts), which play important roles in embryogenesis, organogenesis, adult tissue homeostasis and carcinogenesis. 25447273 1 54 theme glycans 176:182 arg1 biosynthesis 140:151 The biosynthesis 136:151 The biosynthesis of mucin-type O-linked glycans in animals 136:193 The biosynthesis of mucin-type O-linked glycans in animals is initiated by members of the large family of polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts), which play important roles in embryogenesis, organogenesis, adult tissue homeostasis and carcinogenesis. 25447273 6 55 theme expression 1425:1434 arg1 pattern 1436:1442 specific and distinct expression pattern 1403:1442 specific and distinct expression pattern 1403:1442 In summary, these data demonstrate that these two enzymes from different branches of the N-acetylgalactosaminyltransferase do not only display differential substrate specificities, but also specific and distinct expression pattern and biological activities in vivo. 25447273 1 56 theme tissue 368:373 arg1 homeostasis 375:385 adult tissue homeostasis 362:385 adult tissue homeostasis 362:385 The biosynthesis of mucin-type O-linked glycans in animals is initiated by members of the large family of polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts), which play important roles in embryogenesis, organogenesis, adult tissue homeostasis and carcinogenesis. 25447273 3 57 dep N-acetylgalactosaminyltransferases 502:535 arg1 xGalNAc-T16 553:563 xGalNAc-T16 553:563 xGalNAc-T16 553:563 However, two N-acetylgalactosaminyltransferases (xGalNAc-T6 and xGalNAc-T16) from the African clawed frog (Xenopus laevis), which are most homologous to those encoded by the human GALNT6 and GALNT16 (GALNTL1) genes, were shown to have contrasting roles in TGF-β/BMP signaling in embryogenesis. 25447273 3 57 dep N-acetylgalactosaminyltransferases 502:535 arg1 xGalNAc-T6 538:547 xGalNAc-T6 538:547 xGalNAc-T6 538:547 However, two N-acetylgalactosaminyltransferases (xGalNAc-T6 and xGalNAc-T16) from the African clawed frog (Xenopus laevis), which are most homologous to those encoded by the human GALNT6 and GALNT16 (GALNTL1) genes, were shown to have contrasting roles in TGF-β/BMP signaling in embryogenesis. 25447273 3 58 theme African 575:581 arg1 laevis 604:609 the African clawed frog (Xenopus laevis) 571:610 the African clawed frog (Xenopus laevis) 571:610 However, two N-acetylgalactosaminyltransferases (xGalNAc-T6 and xGalNAc-T16) from the African clawed frog (Xenopus laevis), which are most homologous to those encoded by the human GALNT6 and GALNT16 (GALNTL1) genes, were shown to have contrasting roles in TGF-β/BMP signaling in embryogenesis. 25447273 5 59 located found 1038:1042 arg1 terms 991:995 terms 991:995 terms of enzymatic activity 991:1017 In terms of enzymatic activity, both enzymes were found to be active towards the EA2 peptide, but display differential activity towards a peptide based on the sequence of ActR-IIB, a receptor relevant to TGF-β/BMP signaling. 25447273 5 59 located found 1038:1042 arg2 enzymes 1025:1031 both enzymes 1020:1031 both enzymes 1020:1031 In terms of enzymatic activity, both enzymes were found to be active towards the EA2 peptide, but display differential activity towards a peptide based on the sequence of ActR-IIB, a receptor relevant to TGF-β/BMP signaling. 25367160 2 0 theme defined 510:516 arg1 media 518:522 defined media 510:522 defined media 510:522 In order to appreciate the unique properties of these pluripotent, self-renewing cells, we have performed an in-depth multidimensional fractionation followed by LC-MS/MS analysis of the hESCs harvested from defined media to elucidate expressed, phosphorylated, O-linked β-N-acetylglucosamine (O-GlcNAc) modified, and secreted proteins. 25367160 6 1 theme state 1244:1248 arg1 remodeling 1144:1153 remodeling 1144:1153 remodeling 1144:1153 We also identified more than 100 secreted proteins of hESCs that likely play a role in extracellular matrix formation and remodeling, as well as autocrine signaling for self-renewal and maintenance of the undifferentiated state. 25367160 6 1 theme state 1244:1248 arg1 formation 1130:1138 extracellular matrix formation 1109:1138 extracellular matrix formation 1109:1138 We also identified more than 100 secreted proteins of hESCs that likely play a role in extracellular matrix formation and remodeling, as well as autocrine signaling for self-renewal and maintenance of the undifferentiated state. 25367160 6 1 theme state 1244:1248 arg1 signaling 1177:1185 autocrine signaling 1167:1185 autocrine signaling for self-renewal 1167:1202 We also identified more than 100 secreted proteins of hESCs that likely play a role in extracellular matrix formation and remodeling, as well as autocrine signaling for self-renewal and maintenance of the undifferentiated state. 25367160 6 1 theme state 1244:1248 arg1 maintenance 1208:1218 maintenance 1208:1218 maintenance of the undifferentiated state 1208:1248 We also identified more than 100 secreted proteins of hESCs that likely play a role in extracellular matrix formation and remodeling, as well as autocrine signaling for self-renewal and maintenance of the undifferentiated state. 25367160 4 2 theme same 878:881 arg1 confidence 888:897 the same high confidence 874:897 the same high confidence 874:897 This analysis also allowed us to identify nearly 500 phosphorylation sites and 68 sites of O-GlcNAc modification with the same high confidence. 25367160 1 3 theme early 259:263 arg1 development 265:275 early development 259:275 early development 259:275 Human embryonic stem cells (hESCs) have received considerable attention due to their therapeutic potential and usefulness in understanding early development and cell fate commitment. 25367160 2 4 theme pluripotent 357:367 arg1 cells 384:388 these pluripotent, self-renewing cells 351:388 these pluripotent, self-renewing cells 351:388 In order to appreciate the unique properties of these pluripotent, self-renewing cells, we have performed an in-depth multidimensional fractionation followed by LC-MS/MS analysis of the hESCs harvested from defined media to elucidate expressed, phosphorylated, O-linked β-N-acetylglucosamine (O-GlcNAc) modified, and secreted proteins. 25367160 0 5 theme mass 101:104 arg1 spectrometry 106:117 tandem mass spectrometry 94:117 tandem mass spectrometry 94:117 The human embryonic stem cell proteome revealed by multidimensional fractionation followed by tandem mass spectrometry. 25367160 7 6 theme derived 1489:1495 arg1 type 1502:1505 any derived cell type 1485:1505 any derived cell type 1485:1505 Finally, by performing in-depth analysis in triplicate, spectral counts were obtained for these proteins and posttranslationally modified peptides, which will allow us to perform relative quantitative analysis between these cells and any derived cell type in the future. 25367160 2 7 theme secreted 620:627 arg1 proteins 629:636 secreted proteins 620:636 secreted proteins 620:636 In order to appreciate the unique properties of these pluripotent, self-renewing cells, we have performed an in-depth multidimensional fractionation followed by LC-MS/MS analysis of the hESCs harvested from defined media to elucidate expressed, phosphorylated, O-linked β-N-acetylglucosamine (O-GlcNAc) modified, and secreted proteins. 25367160 7 8 theme modified 1380:1387 arg1 peptides 1389:1396 posttranslationally modified peptides 1360:1396 posttranslationally modified peptides 1360:1396 Finally, by performing in-depth analysis in triplicate, spectral counts were obtained for these proteins and posttranslationally modified peptides, which will allow us to perform relative quantitative analysis between these cells and any derived cell type in the future. 25367160 6 9 theme autocrine 1167:1175 arg1 signaling 1177:1185 autocrine signaling 1167:1185 autocrine signaling for self-renewal 1167:1202 We also identified more than 100 secreted proteins of hESCs that likely play a role in extracellular matrix formation and remodeling, as well as autocrine signaling for self-renewal and maintenance of the undifferentiated state. 25367160 0 10 theme tandem 94:99 arg1 spectrometry 106:117 tandem mass spectrometry 94:117 tandem mass spectrometry 94:117 The human embryonic stem cell proteome revealed by multidimensional fractionation followed by tandem mass spectrometry. 25367160 4 11 theme high 883:886 arg1 confidence 888:897 the same high confidence 874:897 the same high confidence 874:897 This analysis also allowed us to identify nearly 500 phosphorylation sites and 68 sites of O-GlcNAc modification with the same high confidence. 25367160 2 12 dep pluripotent 357:367 arg1 self-renewing 370:382 self-renewing 370:382 self-renewing 370:382 In order to appreciate the unique properties of these pluripotent, self-renewing cells, we have performed an in-depth multidimensional fractionation followed by LC-MS/MS analysis of the hESCs harvested from defined media to elucidate expressed, phosphorylated, O-linked β-N-acetylglucosamine (O-GlcNAc) modified, and secreted proteins. 25367160 2 13 link O-linked 564:571 arg1 modified 606:613 modified 606:613 modified 606:613 In order to appreciate the unique properties of these pluripotent, self-renewing cells, we have performed an in-depth multidimensional fractionation followed by LC-MS/MS analysis of the hESCs harvested from defined media to elucidate expressed, phosphorylated, O-linked β-N-acetylglucosamine (O-GlcNAc) modified, and secreted proteins. 25367160 1 14 theme cell 281:284 arg1 commitment 291:300 cell fate commitment 281:300 cell fate commitment 281:300 Human embryonic stem cells (hESCs) have received considerable attention due to their therapeutic potential and usefulness in understanding early development and cell fate commitment. 25367160 3 15 theme false-discovery 734:748 arg1 rate 750:753 less than 1% false-discovery rate 721:753 less than 1% false-discovery rate 721:753 From the triplicate analysis, we were able to assign more than 3000 proteins with less than 1% false-discovery rate. 25367160 4 16 theme O-GlcNAc 847:854 arg1 modification 856:867 O-GlcNAc modification 847:867 O-GlcNAc modification 847:867 This analysis also allowed us to identify nearly 500 phosphorylation sites and 68 sites of O-GlcNAc modification with the same high confidence. 25367160 7 17 theme spectral 1307:1314 arg1 counts 1316:1321 spectral counts 1307:1321 spectral counts 1307:1321 Finally, by performing in-depth analysis in triplicate, spectral counts were obtained for these proteins and posttranslationally modified peptides, which will allow us to perform relative quantitative analysis between these cells and any derived cell type in the future. 25367160 6 18 theme hESCs 1076:1080 arg1 proteins 1064:1071 more than 100 secreted proteins 1041:1071 more than 100 secreted proteins of hESCs that likely play a role in extracellular matrix formation and remodeling, as well as autocrine signaling for self-renewal and maintenance of the undifferentiated state 1041:1248 We also identified more than 100 secreted proteins of hESCs that likely play a role in extracellular matrix formation and remodeling, as well as autocrine signaling for self-renewal and maintenance of the undifferentiated state. 25367160 7 19 theme relative 1430:1437 arg1 analysis 1452:1459 relative quantitative analysis 1430:1459 relative quantitative analysis between these cells 1430:1479 Finally, by performing in-depth analysis in triplicate, spectral counts were obtained for these proteins and posttranslationally modified peptides, which will allow us to perform relative quantitative analysis between these cells and any derived cell type in the future. 25367160 1 20 theme considerable 169:180 arg1 attention 182:190 considerable attention 169:190 considerable attention 169:190 Human embryonic stem cells (hESCs) have received considerable attention due to their therapeutic potential and usefulness in understanding early development and cell fate commitment. 25367160 0 21 theme human 4:8 arg1 proteome 30:37 The human embryonic stem cell proteome 0:37 The human embryonic stem cell proteome 0:37 The human embryonic stem cell proteome revealed by multidimensional fractionation followed by tandem mass spectrometry. 25367160 5 22 from active 999:1004 arg1 cells 1015:1019 these cells 1009:1019 these cells 1009:1019 Investigation of the phosphorylation sites allowed us to deduce the set of kinases that are likely active in these cells. 25367160 3 23 from analysis 659:666 arg1 able 677:680 able 677:680 able 677:680 From the triplicate analysis, we were able to assign more than 3000 proteins with less than 1% false-discovery rate. 25367160 6 24 theme extracellular 1109:1121 arg1 formation 1130:1138 extracellular matrix formation 1109:1138 extracellular matrix formation 1109:1138 We also identified more than 100 secreted proteins of hESCs that likely play a role in extracellular matrix formation and remodeling, as well as autocrine signaling for self-renewal and maintenance of the undifferentiated state. 25367160 2 25 theme LC-MS/MS 464:471 arg1 analysis 473:480 LC-MS/MS analysis 464:480 LC-MS/MS analysis of the hESCs harvested from defined media to elucidate expressed, phosphorylated, O-linked β-N-acetylglucosamine (O-GlcNAc) modified, and secreted proteins 464:636 In order to appreciate the unique properties of these pluripotent, self-renewing cells, we have performed an in-depth multidimensional fractionation followed by LC-MS/MS analysis of the hESCs harvested from defined media to elucidate expressed, phosphorylated, O-linked β-N-acetylglucosamine (O-GlcNAc) modified, and secreted proteins. 25367160 1 26 theme fate 286:289 arg1 commitment 291:300 cell fate commitment 281:300 cell fate commitment 281:300 Human embryonic stem cells (hESCs) have received considerable attention due to their therapeutic potential and usefulness in understanding early development and cell fate commitment. 25367160 4 27 theme modification 856:867 arg1 modification 856:867 O-GlcNAc modification 847:867 O-GlcNAc modification 847:867 This analysis also allowed us to identify nearly 500 phosphorylation sites and 68 sites of O-GlcNAc modification with the same high confidence. 25367160 4 27 theme modification 856:867 arg1 sites 825:829 nearly 500 phosphorylation sites 798:829 nearly 500 phosphorylation sites 798:829 This analysis also allowed us to identify nearly 500 phosphorylation sites and 68 sites of O-GlcNAc modification with the same high confidence. 25367160 4 27 theme modification 856:867 arg1 sites 838:842 68 sites 835:842 68 sites of O-GlcNAc modification 835:867 This analysis also allowed us to identify nearly 500 phosphorylation sites and 68 sites of O-GlcNAc modification with the same high confidence. 25367160 6 28 theme secreted 1055:1062 arg1 proteins 1064:1071 more than 100 secreted proteins 1041:1071 more than 100 secreted proteins of hESCs that likely play a role in extracellular matrix formation and remodeling, as well as autocrine signaling for self-renewal and maintenance of the undifferentiated state 1041:1248 We also identified more than 100 secreted proteins of hESCs that likely play a role in extracellular matrix formation and remodeling, as well as autocrine signaling for self-renewal and maintenance of the undifferentiated state. 25367160 0 29 theme stem 20:23 arg1 proteome 30:37 The human embryonic stem cell proteome 0:37 The human embryonic stem cell proteome 0:37 The human embryonic stem cell proteome revealed by multidimensional fractionation followed by tandem mass spectrometry. 25367160 7 30 link derived 1489:1495 arg1 type 1502:1505 any derived cell type 1485:1505 any derived cell type 1485:1505 Finally, by performing in-depth analysis in triplicate, spectral counts were obtained for these proteins and posttranslationally modified peptides, which will allow us to perform relative quantitative analysis between these cells and any derived cell type in the future. 25367160 0 31 theme embryonic 10:18 arg1 proteome 30:37 The human embryonic stem cell proteome 0:37 The human embryonic stem cell proteome 0:37 The human embryonic stem cell proteome revealed by multidimensional fractionation followed by tandem mass spectrometry. 25367160 2 32 dep elucidate 527:535 arg1 expressed 537:545 expressed 537:545 expressed 537:545 In order to appreciate the unique properties of these pluripotent, self-renewing cells, we have performed an in-depth multidimensional fractionation followed by LC-MS/MS analysis of the hESCs harvested from defined media to elucidate expressed, phosphorylated, O-linked β-N-acetylglucosamine (O-GlcNAc) modified, and secreted proteins. 25367160 5 33 from cells 1015:1019 arg1 active 999:1004 active 999:1004 active 999:1004 Investigation of the phosphorylation sites allowed us to deduce the set of kinases that are likely active in these cells. 25367160 2 34 theme multidimensional 421:436 arg1 fractionation 438:450 an in-depth multidimensional fractionation 409:450 an in-depth multidimensional fractionation followed by LC-MS/MS analysis of the hESCs harvested from defined media to elucidate expressed, phosphorylated, O-linked β-N-acetylglucosamine (O-GlcNAc) modified, and secreted proteins 409:636 In order to appreciate the unique properties of these pluripotent, self-renewing cells, we have performed an in-depth multidimensional fractionation followed by LC-MS/MS analysis of the hESCs harvested from defined media to elucidate expressed, phosphorylated, O-linked β-N-acetylglucosamine (O-GlcNAc) modified, and secreted proteins. 25367160 5 35 theme sites 937:941 arg1 Investigation 900:912 Investigation 900:912 Investigation of the phosphorylation sites 900:941 Investigation of the phosphorylation sites allowed us to deduce the set of kinases that are likely active in these cells. 25367160 1 36 theme therapeutic 205:215 arg1 potential 217:225 their therapeutic potential 199:225 their therapeutic potential 199:225 Human embryonic stem cells (hESCs) have received considerable attention due to their therapeutic potential and usefulness in understanding early development and cell fate commitment. 25367160 6 37 theme undifferentiated 1227:1242 arg1 state 1244:1248 the undifferentiated state 1223:1248 the undifferentiated state 1223:1248 We also identified more than 100 secreted proteins of hESCs that likely play a role in extracellular matrix formation and remodeling, as well as autocrine signaling for self-renewal and maintenance of the undifferentiated state. 25367160 2 38 theme in-depth 412:419 arg1 fractionation 438:450 an in-depth multidimensional fractionation 409:450 an in-depth multidimensional fractionation followed by LC-MS/MS analysis of the hESCs harvested from defined media to elucidate expressed, phosphorylated, O-linked β-N-acetylglucosamine (O-GlcNAc) modified, and secreted proteins 409:636 In order to appreciate the unique properties of these pluripotent, self-renewing cells, we have performed an in-depth multidimensional fractionation followed by LC-MS/MS analysis of the hESCs harvested from defined media to elucidate expressed, phosphorylated, O-linked β-N-acetylglucosamine (O-GlcNAc) modified, and secreted proteins. 25367160 0 39 theme cell 25:28 arg1 proteome 30:37 The human embryonic stem cell proteome 0:37 The human embryonic stem cell proteome 0:37 The human embryonic stem cell proteome revealed by multidimensional fractionation followed by tandem mass spectrometry. 25367160 2 40 theme hESCs 489:493 arg1 analysis 473:480 LC-MS/MS analysis 464:480 LC-MS/MS analysis of the hESCs harvested from defined media to elucidate expressed, phosphorylated, O-linked β-N-acetylglucosamine (O-GlcNAc) modified, and secreted proteins 464:636 In order to appreciate the unique properties of these pluripotent, self-renewing cells, we have performed an in-depth multidimensional fractionation followed by LC-MS/MS analysis of the hESCs harvested from defined media to elucidate expressed, phosphorylated, O-linked β-N-acetylglucosamine (O-GlcNAc) modified, and secreted proteins. 25367160 5 41 theme kinases 975:981 arg1 kinases 975:981 kinases 975:981 kinases that are likely active in these cells 975:1019 Investigation of the phosphorylation sites allowed us to deduce the set of kinases that are likely active in these cells. 25367160 5 41 theme kinases 975:981 arg1 set 968:970 the set 964:970 the set of kinases that are likely active in these cells 964:1019 Investigation of the phosphorylation sites allowed us to deduce the set of kinases that are likely active in these cells. 25367160 1 42 theme Human 120:124 arg1 hESCs 148:152 hESCs 148:152 hESCs 148:152 Human embryonic stem cells (hESCs) have received considerable attention due to their therapeutic potential and usefulness in understanding early development and cell fate commitment. 25367160 1 42 theme Human 120:124 arg1 cells 141:145 Human embryonic stem cells 120:145 Human embryonic stem cells (hESCs) 120:153 Human embryonic stem cells (hESCs) have received considerable attention due to their therapeutic potential and usefulness in understanding early development and cell fate commitment. 25367160 3 43 dep % 732:732 arg1 1 731:731 1 731:731 1 731:731 From the triplicate analysis, we were able to assign more than 3000 proteins with less than 1% false-discovery rate. 25367160 7 44 theme cell 1497:1500 arg1 type 1502:1505 any derived cell type 1485:1505 any derived cell type 1485:1505 Finally, by performing in-depth analysis in triplicate, spectral counts were obtained for these proteins and posttranslationally modified peptides, which will allow us to perform relative quantitative analysis between these cells and any derived cell type in the future. 25367160 7 45 theme in-depth 1274:1281 arg1 analysis 1283:1290 in-depth analysis 1274:1290 in-depth analysis 1274:1290 Finally, by performing in-depth analysis in triplicate, spectral counts were obtained for these proteins and posttranslationally modified peptides, which will allow us to perform relative quantitative analysis between these cells and any derived cell type in the future. 25367160 1 46 theme embryonic 126:134 arg1 hESCs 148:152 hESCs 148:152 hESCs 148:152 Human embryonic stem cells (hESCs) have received considerable attention due to their therapeutic potential and usefulness in understanding early development and cell fate commitment. 25367160 1 46 theme embryonic 126:134 arg1 cells 141:145 Human embryonic stem cells 120:145 Human embryonic stem cells (hESCs) 120:153 Human embryonic stem cells (hESCs) have received considerable attention due to their therapeutic potential and usefulness in understanding early development and cell fate commitment. 25367160 3 47 theme triplicate 648:657 arg1 analysis 659:666 the triplicate analysis 644:666 the triplicate analysis 644:666 From the triplicate analysis, we were able to assign more than 3000 proteins with less than 1% false-discovery rate. 25367160 1 48 theme stem 136:139 arg1 hESCs 148:152 hESCs 148:152 hESCs 148:152 Human embryonic stem cells (hESCs) have received considerable attention due to their therapeutic potential and usefulness in understanding early development and cell fate commitment. 25367160 1 48 theme stem 136:139 arg1 cells 141:145 Human embryonic stem cells 120:145 Human embryonic stem cells (hESCs) 120:153 Human embryonic stem cells (hESCs) have received considerable attention due to their therapeutic potential and usefulness in understanding early development and cell fate commitment. 25367160 5 49 theme phosphorylation 921:935 arg1 sites 937:941 the phosphorylation sites 917:941 the phosphorylation sites 917:941 Investigation of the phosphorylation sites allowed us to deduce the set of kinases that are likely active in these cells. 25367160 7 50 theme quantitative 1439:1450 arg1 analysis 1452:1459 relative quantitative analysis 1430:1459 relative quantitative analysis between these cells 1430:1479 Finally, by performing in-depth analysis in triplicate, spectral counts were obtained for these proteins and posttranslationally modified peptides, which will allow us to perform relative quantitative analysis between these cells and any derived cell type in the future. 25367160 7 51 dep proteins 1347:1354 arg1 these 1341:1345 these 1341:1345 these 1341:1345 Finally, by performing in-depth analysis in triplicate, spectral counts were obtained for these proteins and posttranslationally modified peptides, which will allow us to perform relative quantitative analysis between these cells and any derived cell type in the future. 25367160 2 52 theme unique 330:335 arg1 properties 337:346 the unique properties 326:346 the unique properties of these pluripotent, self-renewing cells 326:388 In order to appreciate the unique properties of these pluripotent, self-renewing cells, we have performed an in-depth multidimensional fractionation followed by LC-MS/MS analysis of the hESCs harvested from defined media to elucidate expressed, phosphorylated, O-linked β-N-acetylglucosamine (O-GlcNAc) modified, and secreted proteins. 25367160 6 53 theme matrix 1123:1128 arg1 formation 1130:1138 extracellular matrix formation 1109:1138 extracellular matrix formation 1109:1138 We also identified more than 100 secreted proteins of hESCs that likely play a role in extracellular matrix formation and remodeling, as well as autocrine signaling for self-renewal and maintenance of the undifferentiated state. 25367160 4 54 theme phosphorylation 809:823 arg1 modification 856:867 O-GlcNAc modification 847:867 O-GlcNAc modification 847:867 This analysis also allowed us to identify nearly 500 phosphorylation sites and 68 sites of O-GlcNAc modification with the same high confidence. 25367160 4 54 theme phosphorylation 809:823 arg1 sites 825:829 nearly 500 phosphorylation sites 798:829 nearly 500 phosphorylation sites 798:829 This analysis also allowed us to identify nearly 500 phosphorylation sites and 68 sites of O-GlcNAc modification with the same high confidence. 25367160 2 55 theme cells 384:388 arg1 properties 337:346 the unique properties 326:346 the unique properties of these pluripotent, self-renewing cells 326:388 In order to appreciate the unique properties of these pluripotent, self-renewing cells, we have performed an in-depth multidimensional fractionation followed by LC-MS/MS analysis of the hESCs harvested from defined media to elucidate expressed, phosphorylated, O-linked β-N-acetylglucosamine (O-GlcNAc) modified, and secreted proteins. 25367160 0 56 theme multidimensional 51:66 arg1 fractionation 68:80 multidimensional fractionation 51:80 multidimensional fractionation followed by tandem mass spectrometry 51:117 The human embryonic stem cell proteome revealed by multidimensional fractionation followed by tandem mass spectrometry. 25367160 3 57 dep rate 750:753 arg1 % 732:732 % 732:732 % 732:732 From the triplicate analysis, we were able to assign more than 3000 proteins with less than 1% false-discovery rate. 25498379 7 0 link N-linked 1288:1295 arg1 family 1310:1315 the small integrin-binding ligand N-linked glycoprotein family 1254:1315 the small integrin-binding ligand N-linked glycoprotein family 1254:1315 Among the numerous noncollagenous bone proteins, we examined matrix Gla protein (MGP), osteocalcin (OC), osteoprotegerin, and the small integrin-binding ligand N-linked glycoprotein family. 25498379 2 1 from markers 314:320 arg1 setting 373:379 the setting 369:379 the setting of chronic kidney disease-mineral and bone disorders (CKD-MBD) 369:442 Accordingly, the diagnostic significance of the classic bone markers of mineral disorders and of the new markers in the setting of chronic kidney disease-mineral and bone disorders (CKD-MBD) needs to be re-evaluated along with increasing information. 25498379 1 2 theme role 72:75 arg1 awareness 45:53 The increased awareness 31:53 The increased awareness of the potential role played by mineral and bone disorder in the appearance of cardiovascular disease in renal patients 31:173 The increased awareness of the potential role played by mineral and bone disorder in the appearance of cardiovascular disease in renal patients has produced research efforts aimed at discovering possible pathogenic links. 25498379 10 3 theme glycoprotein 1707:1718 arg1 proteins 1720:1727 the small integrin-binding ligand N-linked glycoprotein proteins 1664:1727 the small integrin-binding ligand N-linked glycoprotein proteins 1664:1727 Finally, recent acquisitions on the fascinating family of the small integrin-binding ligand N-linked glycoprotein proteins are recapitulated briefly to underline their potential clinical interest and their complex involvement with all aspects of CKD-MBD. 25498379 10 4 theme ligand 1691:1696 arg1 proteins 1720:1727 the small integrin-binding ligand N-linked glycoprotein proteins 1664:1727 the small integrin-binding ligand N-linked glycoprotein proteins 1664:1727 Finally, recent acquisitions on the fascinating family of the small integrin-binding ligand N-linked glycoprotein proteins are recapitulated briefly to underline their potential clinical interest and their complex involvement with all aspects of CKD-MBD. 25498379 4 5 theme collagen-derived 864:879 arg1 peptides 881:888 parathyroid hormone, alkaline phosphatase, tartrate-resistant acid phosphatase, and bone collagen-derived peptides 775:888 parathyroid hormone, alkaline phosphatase, tartrate-resistant acid phosphatase, and bone collagen-derived peptides 775:888 Among classic markers of secondary hyperparathyroidism and of renal osteodystrophy, we analyzed parathyroid hormone, alkaline phosphatase, tartrate-resistant acid phosphatase, and bone collagen-derived peptides. 25498379 10 6 link N-linked 1698:1705 arg1 proteins 1720:1727 the small integrin-binding ligand N-linked glycoprotein proteins 1664:1727 the small integrin-binding ligand N-linked glycoprotein proteins 1664:1727 Finally, recent acquisitions on the fascinating family of the small integrin-binding ligand N-linked glycoprotein proteins are recapitulated briefly to underline their potential clinical interest and their complex involvement with all aspects of CKD-MBD. 25498379 2 7 theme classic 301:307 arg1 markers 314:320 the classic bone markers 297:320 the classic bone markers of mineral disorders and of the new markers in the setting of chronic kidney disease-mineral and bone disorders (CKD-MBD) 297:442 Accordingly, the diagnostic significance of the classic bone markers of mineral disorders and of the new markers in the setting of chronic kidney disease-mineral and bone disorders (CKD-MBD) needs to be re-evaluated along with increasing information. 25498379 9 8 theme vitamin 1597:1603 arg1 deficient 1579:1587 deficient 1579:1587 deficient 1579:1587 Both of these proteins require vitamin K to become active and this is a specific problem in renal patients who frequently are deficient of this vitamin. 25498379 10 9 theme potential 1774:1782 arg1 interest 1793:1800 their potential clinical interest 1768:1800 their potential clinical interest 1768:1800 Finally, recent acquisitions on the fascinating family of the small integrin-binding ligand N-linked glycoprotein proteins are recapitulated briefly to underline their potential clinical interest and their complex involvement with all aspects of CKD-MBD. 25498379 10 10 with interest 1793:1800 arg1 aspects 1841:1847 all aspects 1837:1847 all aspects of CKD-MBD 1837:1858 Finally, recent acquisitions on the fascinating family of the small integrin-binding ligand N-linked glycoprotein proteins are recapitulated briefly to underline their potential clinical interest and their complex involvement with all aspects of CKD-MBD. 25498379 1 11 theme bone 99:102 arg1 disorder 104:111 bone disorder 99:111 bone disorder 99:111 The increased awareness of the potential role played by mineral and bone disorder in the appearance of cardiovascular disease in renal patients has produced research efforts aimed at discovering possible pathogenic links. 25498379 10 12 theme complex 1812:1818 arg1 involvement 1820:1830 their complex involvement 1806:1830 their complex involvement with all aspects of CKD-MBD 1806:1858 Finally, recent acquisitions on the fascinating family of the small integrin-binding ligand N-linked glycoprotein proteins are recapitulated briefly to underline their potential clinical interest and their complex involvement with all aspects of CKD-MBD. 25498379 4 13 theme hyperparathyroidism 714:732 arg1 markers 693:699 classic markers 685:699 classic markers of secondary hyperparathyroidism and of renal osteodystrophy 685:760 Among classic markers of secondary hyperparathyroidism and of renal osteodystrophy, we analyzed parathyroid hormone, alkaline phosphatase, tartrate-resistant acid phosphatase, and bone collagen-derived peptides. 25498379 5 14 theme parent 933:938 arg1 proteins 940:947 parent proteins 933:947 parent proteins (peptides or isoforms) that affect assay methods and, eventually, the diagnostic or prognostic significance 933:1055 We underlined, for each, the relevance of parent proteins (peptides or isoforms) that affect assay methods and, eventually, the diagnostic or prognostic significance. 25498379 11 15 theme further 1911:1917 arg1 studies 1919:1925 further studies 1911:1925 further studies 1911:1925 Their diagnostic role in clinical practice awaits further studies. 25498379 3 16 theme noncollagenous 582:595 arg1 proteins 602:609 the noncollagenous bone proteins 578:609 the noncollagenous bone proteins that are gaining experimental and clinical significance in CKD-MBD 578:676 In this article we include classic markers of bone metabolism and some of the noncollagenous bone proteins that are gaining experimental and clinical significance in CKD-MBD. 25498379 0 17 from biomarkers 8:17 arg1 CKD-MBD 22:28 CKD-MBD 22:28 CKD-MBD 22:28 News on biomarkers in CKD-MBD. 25498379 4 18 theme classic 685:691 arg1 markers 693:699 classic markers 685:699 classic markers of secondary hyperparathyroidism and of renal osteodystrophy 685:760 Among classic markers of secondary hyperparathyroidism and of renal osteodystrophy, we analyzed parathyroid hormone, alkaline phosphatase, tartrate-resistant acid phosphatase, and bone collagen-derived peptides. 25498379 1 19 theme cardiovascular 134:147 arg1 disease 149:155 cardiovascular disease 134:155 cardiovascular disease 134:155 The increased awareness of the potential role played by mineral and bone disorder in the appearance of cardiovascular disease in renal patients has produced research efforts aimed at discovering possible pathogenic links. 25498379 0 20 from News 0:3 arg1 biomarkers 8:17 biomarkers 8:17 biomarkers in CKD-MBD 8:28 News on biomarkers in CKD-MBD. 25498379 2 21 theme diagnostic 270:279 arg1 significance 281:292 the diagnostic significance 266:292 the diagnostic significance of the classic bone markers of mineral disorders and of the new markers in the setting of chronic kidney disease-mineral and bone disorders (CKD-MBD) 266:442 Accordingly, the diagnostic significance of the classic bone markers of mineral disorders and of the new markers in the setting of chronic kidney disease-mineral and bone disorders (CKD-MBD) needs to be re-evaluated along with increasing information. 25498379 10 22 theme recent 1615:1620 arg1 acquisitions 1622:1633 recent acquisitions 1615:1633 recent acquisitions on the fascinating family of the small integrin-binding ligand N-linked glycoprotein proteins 1615:1727 Finally, recent acquisitions on the fascinating family of the small integrin-binding ligand N-linked glycoprotein proteins are recapitulated briefly to underline their potential clinical interest and their complex involvement with all aspects of CKD-MBD. 25498379 4 23 theme parathyroid 775:785 arg1 hormone 787:793 parathyroid hormone 775:793 parathyroid hormone 775:793 Among classic markers of secondary hyperparathyroidism and of renal osteodystrophy, we analyzed parathyroid hormone, alkaline phosphatase, tartrate-resistant acid phosphatase, and bone collagen-derived peptides. 25498379 1 24 theme potential 62:70 arg1 role 72:75 the potential role 58:75 the potential role played by mineral and bone disorder in the appearance of cardiovascular disease in renal patients 58:173 The increased awareness of the potential role played by mineral and bone disorder in the appearance of cardiovascular disease in renal patients has produced research efforts aimed at discovering possible pathogenic links. 25498379 8 25 theme relevant 1347:1354 arg1 involvement 1356:1366 the relevant involvement 1343:1366 the relevant involvement with the process of calcification (MGP) and with glucose and energy metabolism (OC) 1343:1450 For MGP and OC we report the relevant involvement with the process of calcification (MGP) and with glucose and energy metabolism (OC). 25498379 11 26 theme diagnostic 1867:1876 arg1 role 1878:1881 Their diagnostic role 1861:1881 Their diagnostic role in clinical practice 1861:1902 Their diagnostic role in clinical practice awaits further studies. 25498379 7 27 theme matrix 1189:1194 arg1 MGP 1209:1211 MGP 1209:1211 MGP 1209:1211 Among the numerous noncollagenous bone proteins, we examined matrix Gla protein (MGP), osteocalcin (OC), osteoprotegerin, and the small integrin-binding ligand N-linked glycoprotein family. 25498379 7 27 theme matrix 1189:1194 arg1 protein 1200:1206 matrix Gla protein 1189:1206 matrix Gla protein (MGP) 1189:1212 Among the numerous noncollagenous bone proteins, we examined matrix Gla protein (MGP), osteocalcin (OC), osteoprotegerin, and the small integrin-binding ligand N-linked glycoprotein family. 25498379 2 28 theme bone 419:422 arg1 disorders 424:432 bone disorders 419:432 bone disorders (CKD-MBD) 419:442 Accordingly, the diagnostic significance of the classic bone markers of mineral disorders and of the new markers in the setting of chronic kidney disease-mineral and bone disorders (CKD-MBD) needs to be re-evaluated along with increasing information. 25498379 2 28 theme bone 419:422 arg1 CKD-MBD 435:441 CKD-MBD 435:441 CKD-MBD 435:441 Accordingly, the diagnostic significance of the classic bone markers of mineral disorders and of the new markers in the setting of chronic kidney disease-mineral and bone disorders (CKD-MBD) needs to be re-evaluated along with increasing information. 25498379 4 29 theme osteodystrophy 747:760 arg1 markers 693:699 classic markers 685:699 classic markers of secondary hyperparathyroidism and of renal osteodystrophy 685:760 Among classic markers of secondary hyperparathyroidism and of renal osteodystrophy, we analyzed parathyroid hormone, alkaline phosphatase, tartrate-resistant acid phosphatase, and bone collagen-derived peptides. 25498379 2 30 theme disease-mineral 399:413 arg1 setting 373:379 the setting 369:379 the setting of chronic kidney disease-mineral and bone disorders (CKD-MBD) 369:442 Accordingly, the diagnostic significance of the classic bone markers of mineral disorders and of the new markers in the setting of chronic kidney disease-mineral and bone disorders (CKD-MBD) needs to be re-evaluated along with increasing information. 25498379 11 31 from role 1878:1881 arg1 practice 1895:1902 clinical practice 1886:1902 clinical practice 1886:1902 Their diagnostic role in clinical practice awaits further studies. 25498379 9 32 theme specific 1525:1532 arg1 problem 1534:1540 a specific problem 1523:1540 a specific problem in renal patients who frequently are deficient of this vitamin 1523:1603 Both of these proteins require vitamin K to become active and this is a specific problem in renal patients who frequently are deficient of this vitamin. 25498379 9 32 theme specific 1525:1532 arg1 this 1515:1518 this 1515:1518 this 1515:1518 Both of these proteins require vitamin K to become active and this is a specific problem in renal patients who frequently are deficient of this vitamin. 25498379 9 33 from problem 1534:1540 arg1 patients 1551:1558 renal patients 1545:1558 renal patients who frequently are deficient of this vitamin 1545:1603 Both of these proteins require vitamin K to become active and this is a specific problem in renal patients who frequently are deficient of this vitamin. 25498379 7 34 theme glycoprotein 1297:1308 arg1 family 1310:1315 the small integrin-binding ligand N-linked glycoprotein family 1254:1315 the small integrin-binding ligand N-linked glycoprotein family 1254:1315 Among the numerous noncollagenous bone proteins, we examined matrix Gla protein (MGP), osteocalcin (OC), osteoprotegerin, and the small integrin-binding ligand N-linked glycoprotein family. 25498379 10 35 with involvement 1820:1830 arg1 aspects 1841:1847 all aspects 1837:1847 all aspects of CKD-MBD 1837:1858 Finally, recent acquisitions on the fascinating family of the small integrin-binding ligand N-linked glycoprotein proteins are recapitulated briefly to underline their potential clinical interest and their complex involvement with all aspects of CKD-MBD. 25498379 3 36 theme experimental 628:639 arg1 significance 654:665 experimental and clinical significance 628:665 experimental and clinical significance 628:665 In this article we include classic markers of bone metabolism and some of the noncollagenous bone proteins that are gaining experimental and clinical significance in CKD-MBD. 25498379 4 37 theme tartrate-resistant 818:835 arg1 phosphatase 842:852 tartrate-resistant acid phosphatase 818:852 tartrate-resistant acid phosphatase 818:852 Among classic markers of secondary hyperparathyroidism and of renal osteodystrophy, we analyzed parathyroid hormone, alkaline phosphatase, tartrate-resistant acid phosphatase, and bone collagen-derived peptides. 25498379 2 38 theme chronic 384:390 arg1 disease-mineral 399:413 chronic kidney disease-mineral 384:413 chronic kidney disease-mineral 384:413 Accordingly, the diagnostic significance of the classic bone markers of mineral disorders and of the new markers in the setting of chronic kidney disease-mineral and bone disorders (CKD-MBD) needs to be re-evaluated along with increasing information. 25498379 10 39 gly glycoprotein 1707:1718 arg1 glycoprotein 1707:1718 the small integrin-binding ligand N-linked glycoprotein proteins 1664:1727 the small integrin-binding ligand N-linked glycoprotein proteins 1664:1727 Finally, recent acquisitions on the fascinating family of the small integrin-binding ligand N-linked glycoprotein proteins are recapitulated briefly to underline their potential clinical interest and their complex involvement with all aspects of CKD-MBD. 25498379 7 40 theme ligand 1281:1286 arg1 family 1310:1315 the small integrin-binding ligand N-linked glycoprotein family 1254:1315 the small integrin-binding ligand N-linked glycoprotein family 1254:1315 Among the numerous noncollagenous bone proteins, we examined matrix Gla protein (MGP), osteocalcin (OC), osteoprotegerin, and the small integrin-binding ligand N-linked glycoprotein family. 25498379 4 41 theme phosphatase 842:852 arg1 peptides 881:888 parathyroid hormone, alkaline phosphatase, tartrate-resistant acid phosphatase, and bone collagen-derived peptides 775:888 parathyroid hormone, alkaline phosphatase, tartrate-resistant acid phosphatase, and bone collagen-derived peptides 775:888 Among classic markers of secondary hyperparathyroidism and of renal osteodystrophy, we analyzed parathyroid hormone, alkaline phosphatase, tartrate-resistant acid phosphatase, and bone collagen-derived peptides. 25498379 2 42 theme disorders 333:341 arg1 markers 314:320 the classic bone markers 297:320 the classic bone markers of mineral disorders and of the new markers in the setting of chronic kidney disease-mineral and bone disorders (CKD-MBD) 297:442 Accordingly, the diagnostic significance of the classic bone markers of mineral disorders and of the new markers in the setting of chronic kidney disease-mineral and bone disorders (CKD-MBD) needs to be re-evaluated along with increasing information. 25498379 7 43 theme noncollagenous 1147:1160 arg1 proteins 1167:1174 the numerous noncollagenous bone proteins 1134:1174 the numerous noncollagenous bone proteins 1134:1174 Among the numerous noncollagenous bone proteins, we examined matrix Gla protein (MGP), osteocalcin (OC), osteoprotegerin, and the small integrin-binding ligand N-linked glycoprotein family. 25498379 5 44 theme diagnostic 1019:1028 arg1 significance 1044:1055 the diagnostic or prognostic significance 1015:1055 the diagnostic or prognostic significance 1015:1055 We underlined, for each, the relevance of parent proteins (peptides or isoforms) that affect assay methods and, eventually, the diagnostic or prognostic significance. 25498379 2 45 from setting 373:379 arg1 markers 314:320 the classic bone markers 297:320 the classic bone markers of mineral disorders and of the new markers in the setting of chronic kidney disease-mineral and bone disorders (CKD-MBD) 297:442 Accordingly, the diagnostic significance of the classic bone markers of mineral disorders and of the new markers in the setting of chronic kidney disease-mineral and bone disorders (CKD-MBD) needs to be re-evaluated along with increasing information. 25498379 7 46 theme small 1258:1262 arg1 family 1310:1315 the small integrin-binding ligand N-linked glycoprotein family 1254:1315 the small integrin-binding ligand N-linked glycoprotein family 1254:1315 Among the numerous noncollagenous bone proteins, we examined matrix Gla protein (MGP), osteocalcin (OC), osteoprotegerin, and the small integrin-binding ligand N-linked glycoprotein family. 25498379 3 47 theme clinical 645:652 arg1 significance 654:665 experimental and clinical significance 628:665 experimental and clinical significance 628:665 In this article we include classic markers of bone metabolism and some of the noncollagenous bone proteins that are gaining experimental and clinical significance in CKD-MBD. 25498379 4 48 theme phosphatase 805:815 arg1 peptides 881:888 parathyroid hormone, alkaline phosphatase, tartrate-resistant acid phosphatase, and bone collagen-derived peptides 775:888 parathyroid hormone, alkaline phosphatase, tartrate-resistant acid phosphatase, and bone collagen-derived peptides 775:888 Among classic markers of secondary hyperparathyroidism and of renal osteodystrophy, we analyzed parathyroid hormone, alkaline phosphatase, tartrate-resistant acid phosphatase, and bone collagen-derived peptides. 25498379 10 49 theme integrin-binding 1674:1689 arg1 proteins 1720:1727 the small integrin-binding ligand N-linked glycoprotein proteins 1664:1727 the small integrin-binding ligand N-linked glycoprotein proteins 1664:1727 Finally, recent acquisitions on the fascinating family of the small integrin-binding ligand N-linked glycoprotein proteins are recapitulated briefly to underline their potential clinical interest and their complex involvement with all aspects of CKD-MBD. 25498379 1 50 theme increased 35:43 arg1 awareness 45:53 The increased awareness 31:53 The increased awareness of the potential role played by mineral and bone disorder in the appearance of cardiovascular disease in renal patients 31:173 The increased awareness of the potential role played by mineral and bone disorder in the appearance of cardiovascular disease in renal patients has produced research efforts aimed at discovering possible pathogenic links. 25498379 10 51 from acquisitions 1622:1633 arg1 family 1654:1659 the fascinating family 1638:1659 the fascinating family of the small integrin-binding ligand N-linked glycoprotein proteins 1638:1727 Finally, recent acquisitions on the fascinating family of the small integrin-binding ligand N-linked glycoprotein proteins are recapitulated briefly to underline their potential clinical interest and their complex involvement with all aspects of CKD-MBD. 25498379 1 52 theme pathogenic 235:244 arg1 links 246:250 possible pathogenic links 226:250 possible pathogenic links 226:250 The increased awareness of the potential role played by mineral and bone disorder in the appearance of cardiovascular disease in renal patients has produced research efforts aimed at discovering possible pathogenic links. 25498379 8 53 theme calcification 1388:1400 arg1 process 1377:1383 the process 1373:1383 the process of calcification (MGP) 1373:1406 For MGP and OC we report the relevant involvement with the process of calcification (MGP) and with glucose and energy metabolism (OC). 25498379 10 54 theme proteins 1720:1727 arg1 family 1654:1659 the fascinating family 1638:1659 the fascinating family of the small integrin-binding ligand N-linked glycoprotein proteins 1638:1727 Finally, recent acquisitions on the fascinating family of the small integrin-binding ligand N-linked glycoprotein proteins are recapitulated briefly to underline their potential clinical interest and their complex involvement with all aspects of CKD-MBD. 25498379 6 55 with relationship 1084:1095 arg1 mortality 1117:1125 cardiovascular mortality 1102:1125 cardiovascular mortality 1102:1125 Also, we considered their relationship with cardiovascular mortality. 25498379 5 56 dep proteins 940:947 arg1 peptides 950:957 peptides 950:957 peptides 950:957 We underlined, for each, the relevance of parent proteins (peptides or isoforms) that affect assay methods and, eventually, the diagnostic or prognostic significance. 25498379 5 56 dep proteins 940:947 arg1 isoforms 962:969 isoforms 962:969 isoforms 962:969 We underlined, for each, the relevance of parent proteins (peptides or isoforms) that affect assay methods and, eventually, the diagnostic or prognostic significance. 25498379 10 57 theme N-linked 1698:1705 arg1 proteins 1720:1727 the small integrin-binding ligand N-linked glycoprotein proteins 1664:1727 the small integrin-binding ligand N-linked glycoprotein proteins 1664:1727 Finally, recent acquisitions on the fascinating family of the small integrin-binding ligand N-linked glycoprotein proteins are recapitulated briefly to underline their potential clinical interest and their complex involvement with all aspects of CKD-MBD. 25498379 1 58 theme disease 149:155 arg1 appearance 120:129 the appearance 116:129 the appearance of cardiovascular disease in renal patients 116:173 The increased awareness of the potential role played by mineral and bone disorder in the appearance of cardiovascular disease in renal patients has produced research efforts aimed at discovering possible pathogenic links. 25498379 2 59 theme bone 309:312 arg1 markers 314:320 the classic bone markers 297:320 the classic bone markers of mineral disorders and of the new markers in the setting of chronic kidney disease-mineral and bone disorders (CKD-MBD) 297:442 Accordingly, the diagnostic significance of the classic bone markers of mineral disorders and of the new markers in the setting of chronic kidney disease-mineral and bone disorders (CKD-MBD) needs to be re-evaluated along with increasing information. 25498379 1 60 theme renal 160:164 arg1 patients 166:173 renal patients 160:173 renal patients 160:173 The increased awareness of the potential role played by mineral and bone disorder in the appearance of cardiovascular disease in renal patients has produced research efforts aimed at discovering possible pathogenic links. 25498379 4 61 theme bone 859:862 arg1 peptides 881:888 parathyroid hormone, alkaline phosphatase, tartrate-resistant acid phosphatase, and bone collagen-derived peptides 775:888 parathyroid hormone, alkaline phosphatase, tartrate-resistant acid phosphatase, and bone collagen-derived peptides 775:888 Among classic markers of secondary hyperparathyroidism and of renal osteodystrophy, we analyzed parathyroid hormone, alkaline phosphatase, tartrate-resistant acid phosphatase, and bone collagen-derived peptides. 25498379 3 62 theme classic 531:537 arg1 markers 539:545 classic markers 531:545 classic markers of bone metabolism 531:564 In this article we include classic markers of bone metabolism and some of the noncollagenous bone proteins that are gaining experimental and clinical significance in CKD-MBD. 25498379 3 63 theme bone 550:553 arg1 metabolism 555:564 bone metabolism 550:564 bone metabolism 550:564 In this article we include classic markers of bone metabolism and some of the noncollagenous bone proteins that are gaining experimental and clinical significance in CKD-MBD. 25498379 2 64 theme new 354:356 arg1 markers 358:364 the new markers 350:364 the new markers in the setting of chronic kidney disease-mineral and bone disorders (CKD-MBD) 350:442 Accordingly, the diagnostic significance of the classic bone markers of mineral disorders and of the new markers in the setting of chronic kidney disease-mineral and bone disorders (CKD-MBD) needs to be re-evaluated along with increasing information. 25498379 4 65 link collagen-derived 864:879 arg1 peptides 881:888 parathyroid hormone, alkaline phosphatase, tartrate-resistant acid phosphatase, and bone collagen-derived peptides 775:888 parathyroid hormone, alkaline phosphatase, tartrate-resistant acid phosphatase, and bone collagen-derived peptides 775:888 Among classic markers of secondary hyperparathyroidism and of renal osteodystrophy, we analyzed parathyroid hormone, alkaline phosphatase, tartrate-resistant acid phosphatase, and bone collagen-derived peptides. 25498379 10 66 theme fascinating 1642:1652 arg1 family 1654:1659 the fascinating family 1638:1659 the fascinating family of the small integrin-binding ligand N-linked glycoprotein proteins 1638:1727 Finally, recent acquisitions on the fascinating family of the small integrin-binding ligand N-linked glycoprotein proteins are recapitulated briefly to underline their potential clinical interest and their complex involvement with all aspects of CKD-MBD. 25498379 10 67 theme clinical 1784:1791 arg1 interest 1793:1800 their potential clinical interest 1768:1800 their potential clinical interest 1768:1800 Finally, recent acquisitions on the fascinating family of the small integrin-binding ligand N-linked glycoprotein proteins are recapitulated briefly to underline their potential clinical interest and their complex involvement with all aspects of CKD-MBD. 25498379 1 68 theme research 188:195 arg1 efforts 197:203 research efforts 188:203 research efforts aimed at discovering possible pathogenic links 188:250 The increased awareness of the potential role played by mineral and bone disorder in the appearance of cardiovascular disease in renal patients has produced research efforts aimed at discovering possible pathogenic links. 25498379 8 69 theme energy 1429:1434 arg1 OC 1448:1449 OC 1448:1449 OC 1448:1449 For MGP and OC we report the relevant involvement with the process of calcification (MGP) and with glucose and energy metabolism (OC). 25498379 8 69 theme energy 1429:1434 arg1 metabolism 1436:1445 energy metabolism 1429:1445 energy metabolism (OC) 1429:1450 For MGP and OC we report the relevant involvement with the process of calcification (MGP) and with glucose and energy metabolism (OC). 25498379 3 70 theme metabolism 555:564 arg1 markers 539:545 classic markers 531:545 classic markers of bone metabolism 531:564 In this article we include classic markers of bone metabolism and some of the noncollagenous bone proteins that are gaining experimental and clinical significance in CKD-MBD. 25498379 5 71 theme prognostic 1033:1042 arg1 significance 1044:1055 the diagnostic or prognostic significance 1015:1055 the diagnostic or prognostic significance 1015:1055 We underlined, for each, the relevance of parent proteins (peptides or isoforms) that affect assay methods and, eventually, the diagnostic or prognostic significance. 25498379 3 72 theme bone 597:600 arg1 proteins 602:609 the noncollagenous bone proteins 578:609 the noncollagenous bone proteins that are gaining experimental and clinical significance in CKD-MBD 578:676 In this article we include classic markers of bone metabolism and some of the noncollagenous bone proteins that are gaining experimental and clinical significance in CKD-MBD. 25498379 4 73 theme secondary 704:712 arg1 hyperparathyroidism 714:732 secondary hyperparathyroidism 704:732 secondary hyperparathyroidism 704:732 Among classic markers of secondary hyperparathyroidism and of renal osteodystrophy, we analyzed parathyroid hormone, alkaline phosphatase, tartrate-resistant acid phosphatase, and bone collagen-derived peptides. 25498379 7 74 gly glycoprotein 1297:1308 arg1 glycoprotein 1297:1308 the small integrin-binding ligand N-linked glycoprotein family 1254:1315 the small integrin-binding ligand N-linked glycoprotein family 1254:1315 Among the numerous noncollagenous bone proteins, we examined matrix Gla protein (MGP), osteocalcin (OC), osteoprotegerin, and the small integrin-binding ligand N-linked glycoprotein family. 25498379 9 75 theme vitamin 1484:1490 arg1 K 1492:1492 vitamin K 1484:1492 vitamin K 1484:1492 Both of these proteins require vitamin K to become active and this is a specific problem in renal patients who frequently are deficient of this vitamin. 25498379 8 76 with involvement 1356:1366 arg1 OC 1448:1449 OC 1448:1449 OC 1448:1449 For MGP and OC we report the relevant involvement with the process of calcification (MGP) and with glucose and energy metabolism (OC). 25498379 8 76 with involvement 1356:1366 arg1 glucose 1417:1423 glucose 1417:1423 glucose 1417:1423 For MGP and OC we report the relevant involvement with the process of calcification (MGP) and with glucose and energy metabolism (OC). 25498379 8 76 with involvement 1356:1366 arg1 metabolism 1436:1445 energy metabolism 1429:1445 energy metabolism (OC) 1429:1450 For MGP and OC we report the relevant involvement with the process of calcification (MGP) and with glucose and energy metabolism (OC). 25498379 8 76 with involvement 1356:1366 arg1 process 1377:1383 the process 1373:1383 the process of calcification (MGP) 1373:1406 For MGP and OC we report the relevant involvement with the process of calcification (MGP) and with glucose and energy metabolism (OC). 25498379 7 77 theme Gla 1196:1198 arg1 MGP 1209:1211 MGP 1209:1211 MGP 1209:1211 Among the numerous noncollagenous bone proteins, we examined matrix Gla protein (MGP), osteocalcin (OC), osteoprotegerin, and the small integrin-binding ligand N-linked glycoprotein family. 25498379 7 77 theme Gla 1196:1198 arg1 protein 1200:1206 matrix Gla protein 1189:1206 matrix Gla protein (MGP) 1189:1212 Among the numerous noncollagenous bone proteins, we examined matrix Gla protein (MGP), osteocalcin (OC), osteoprotegerin, and the small integrin-binding ligand N-linked glycoprotein family. 25498379 1 78 from appearance 120:129 arg1 patients 166:173 renal patients 160:173 renal patients 160:173 The increased awareness of the potential role played by mineral and bone disorder in the appearance of cardiovascular disease in renal patients has produced research efforts aimed at discovering possible pathogenic links. 25498379 11 79 theme clinical 1886:1893 arg1 practice 1895:1902 clinical practice 1886:1902 clinical practice 1886:1902 Their diagnostic role in clinical practice awaits further studies. 25498379 5 80 theme proteins 940:947 arg1 relevance 920:928 the relevance 916:928 the relevance of parent proteins (peptides or isoforms) that affect assay methods and, eventually, the diagnostic or prognostic significance 916:1055 We underlined, for each, the relevance of parent proteins (peptides or isoforms) that affect assay methods and, eventually, the diagnostic or prognostic significance. 25498379 2 81 theme disorders 424:432 arg1 setting 373:379 the setting 369:379 the setting of chronic kidney disease-mineral and bone disorders (CKD-MBD) 369:442 Accordingly, the diagnostic significance of the classic bone markers of mineral disorders and of the new markers in the setting of chronic kidney disease-mineral and bone disorders (CKD-MBD) needs to be re-evaluated along with increasing information. 25498379 2 82 theme markers 358:364 arg1 markers 314:320 the classic bone markers 297:320 the classic bone markers of mineral disorders and of the new markers in the setting of chronic kidney disease-mineral and bone disorders (CKD-MBD) 297:442 Accordingly, the diagnostic significance of the classic bone markers of mineral disorders and of the new markers in the setting of chronic kidney disease-mineral and bone disorders (CKD-MBD) needs to be re-evaluated along with increasing information. 25498379 7 83 theme N-linked 1288:1295 arg1 family 1310:1315 the small integrin-binding ligand N-linked glycoprotein family 1254:1315 the small integrin-binding ligand N-linked glycoprotein family 1254:1315 Among the numerous noncollagenous bone proteins, we examined matrix Gla protein (MGP), osteocalcin (OC), osteoprotegerin, and the small integrin-binding ligand N-linked glycoprotein family. 25498379 4 84 theme renal 741:745 arg1 osteodystrophy 747:760 renal osteodystrophy 741:760 renal osteodystrophy 741:760 Among classic markers of secondary hyperparathyroidism and of renal osteodystrophy, we analyzed parathyroid hormone, alkaline phosphatase, tartrate-resistant acid phosphatase, and bone collagen-derived peptides. 25498379 2 85 theme kidney 392:397 arg1 disease-mineral 399:413 chronic kidney disease-mineral 384:413 chronic kidney disease-mineral 384:413 Accordingly, the diagnostic significance of the classic bone markers of mineral disorders and of the new markers in the setting of chronic kidney disease-mineral and bone disorders (CKD-MBD) needs to be re-evaluated along with increasing information. 25498379 7 86 theme bone 1162:1165 arg1 proteins 1167:1174 the numerous noncollagenous bone proteins 1134:1174 the numerous noncollagenous bone proteins 1134:1174 Among the numerous noncollagenous bone proteins, we examined matrix Gla protein (MGP), osteocalcin (OC), osteoprotegerin, and the small integrin-binding ligand N-linked glycoprotein family. 25498379 7 87 theme integrin-binding 1264:1279 arg1 family 1310:1315 the small integrin-binding ligand N-linked glycoprotein family 1254:1315 the small integrin-binding ligand N-linked glycoprotein family 1254:1315 Among the numerous noncollagenous bone proteins, we examined matrix Gla protein (MGP), osteocalcin (OC), osteoprotegerin, and the small integrin-binding ligand N-linked glycoprotein family. 25498379 7 88 theme numerous 1138:1145 arg1 proteins 1167:1174 the numerous noncollagenous bone proteins 1134:1174 the numerous noncollagenous bone proteins 1134:1174 Among the numerous noncollagenous bone proteins, we examined matrix Gla protein (MGP), osteocalcin (OC), osteoprotegerin, and the small integrin-binding ligand N-linked glycoprotein family. 25498379 2 89 dep re-evaluated 456:467 arg1 increasing 480:489 increasing 480:489 increasing information 480:501 Accordingly, the diagnostic significance of the classic bone markers of mineral disorders and of the new markers in the setting of chronic kidney disease-mineral and bone disorders (CKD-MBD) needs to be re-evaluated along with increasing information. 25498379 9 90 theme renal 1545:1549 arg1 patients 1551:1558 renal patients 1545:1558 renal patients who frequently are deficient of this vitamin 1545:1603 Both of these proteins require vitamin K to become active and this is a specific problem in renal patients who frequently are deficient of this vitamin. 25498379 2 91 from markers 358:364 arg1 setting 373:379 the setting 369:379 the setting of chronic kidney disease-mineral and bone disorders (CKD-MBD) 369:442 Accordingly, the diagnostic significance of the classic bone markers of mineral disorders and of the new markers in the setting of chronic kidney disease-mineral and bone disorders (CKD-MBD) needs to be re-evaluated along with increasing information. 25498379 4 92 theme acid 837:840 arg1 phosphatase 842:852 tartrate-resistant acid phosphatase 818:852 tartrate-resistant acid phosphatase 818:852 Among classic markers of secondary hyperparathyroidism and of renal osteodystrophy, we analyzed parathyroid hormone, alkaline phosphatase, tartrate-resistant acid phosphatase, and bone collagen-derived peptides. 25498379 2 93 theme mineral 325:331 arg1 disorders 333:341 mineral disorders 325:341 mineral disorders 325:341 Accordingly, the diagnostic significance of the classic bone markers of mineral disorders and of the new markers in the setting of chronic kidney disease-mineral and bone disorders (CKD-MBD) needs to be re-evaluated along with increasing information. 25498379 5 94 theme assay 984:988 arg1 methods 990:996 assay methods 984:996 assay methods 984:996 We underlined, for each, the relevance of parent proteins (peptides or isoforms) that affect assay methods and, eventually, the diagnostic or prognostic significance. 25498379 10 95 theme CKD-MBD 1852:1858 arg1 aspects 1841:1847 all aspects 1837:1847 all aspects of CKD-MBD 1837:1858 Finally, recent acquisitions on the fascinating family of the small integrin-binding ligand N-linked glycoprotein proteins are recapitulated briefly to underline their potential clinical interest and their complex involvement with all aspects of CKD-MBD. 25498379 4 96 theme hormone 787:793 arg1 peptides 881:888 parathyroid hormone, alkaline phosphatase, tartrate-resistant acid phosphatase, and bone collagen-derived peptides 775:888 parathyroid hormone, alkaline phosphatase, tartrate-resistant acid phosphatase, and bone collagen-derived peptides 775:888 Among classic markers of secondary hyperparathyroidism and of renal osteodystrophy, we analyzed parathyroid hormone, alkaline phosphatase, tartrate-resistant acid phosphatase, and bone collagen-derived peptides. 25498379 2 97 theme markers 314:320 arg1 significance 281:292 the diagnostic significance 266:292 the diagnostic significance of the classic bone markers of mineral disorders and of the new markers in the setting of chronic kidney disease-mineral and bone disorders (CKD-MBD) 266:442 Accordingly, the diagnostic significance of the classic bone markers of mineral disorders and of the new markers in the setting of chronic kidney disease-mineral and bone disorders (CKD-MBD) needs to be re-evaluated along with increasing information. 25498379 6 98 theme cardiovascular 1102:1115 arg1 mortality 1117:1125 cardiovascular mortality 1102:1125 cardiovascular mortality 1102:1125 Also, we considered their relationship with cardiovascular mortality. 25498379 4 99 theme alkaline 796:803 arg1 phosphatase 805:815 alkaline phosphatase 796:815 alkaline phosphatase 796:815 Among classic markers of secondary hyperparathyroidism and of renal osteodystrophy, we analyzed parathyroid hormone, alkaline phosphatase, tartrate-resistant acid phosphatase, and bone collagen-derived peptides. 25498379 10 100 theme small 1668:1672 arg1 proteins 1720:1727 the small integrin-binding ligand N-linked glycoprotein proteins 1664:1727 the small integrin-binding ligand N-linked glycoprotein proteins 1664:1727 Finally, recent acquisitions on the fascinating family of the small integrin-binding ligand N-linked glycoprotein proteins are recapitulated briefly to underline their potential clinical interest and their complex involvement with all aspects of CKD-MBD. 25498379 1 101 theme possible 226:233 arg1 links 246:250 possible pathogenic links 226:250 possible pathogenic links 226:250 The increased awareness of the potential role played by mineral and bone disorder in the appearance of cardiovascular disease in renal patients has produced research efforts aimed at discovering possible pathogenic links. 27614974 12 0 theme background 2006:2015 arg1 ions 2017:2020 background ions 2006:2020 background ions from proteins or other interferents 2006:2056 In cases where background ions from proteins or other interferents are high, usage of an inclusion list is even more advantageous. 27614974 7 1 theme inclusion 1204:1212 arg1 lists 1214:1218 inclusion lists 1204:1218 inclusion lists for these types of analyses 1204:1246 However, due to the massive heterogeneity of glycopeptides, it is not obvious how to expediently generate inclusion lists for these types of analyses. 27614974 12 2 from advantageous 2108:2119 arg1 cases 1994:1998 cases 1994:1998 cases where background ions from proteins or other interferents are high 1994:2065 In cases where background ions from proteins or other interferents are high, usage of an inclusion list is even more advantageous. 27614974 1 3 theme essential 246:254 arg1 development 196:206 the development 192:206 the development of tools to study glycosylation 192:238 Protein glycosylation drives many biological processes and serves as markers for disease; therefore, the development of tools to study glycosylation is an essential and growing area of research. 27614974 1 3 theme essential 246:254 arg1 area 268:271 an essential and growing area 243:271 an essential and growing area of research 243:283 Protein glycosylation drives many biological processes and serves as markers for disease; therefore, the development of tools to study glycosylation is an essential and growing area of research. 27614974 2 4 theme mass 572:575 arg1 spectrometry 577:588 tandem mass spectrometry 565:588 tandem mass spectrometry (MS/MS) 565:596 Mass spectrometry can be used to identify both the glycans of interest and the glycosylation sites to which those glycans are attached, when proteins are proteolytically digested and their glycopeptides are analyzed by a combination of high-resolution mass spectrometry (MS) and tandem mass spectrometry (MS/MS) methods. 27614974 2 4 theme mass 572:575 arg1 MS/MS 591:595 MS/MS 591:595 MS/MS 591:595 Mass spectrometry can be used to identify both the glycans of interest and the glycosylation sites to which those glycans are attached, when proteins are proteolytically digested and their glycopeptides are analyzed by a combination of high-resolution mass spectrometry (MS) and tandem mass spectrometry (MS/MS) methods. 27614974 2 5 gly glycopeptides 475:487 arg2 glycopeptides 475:487 their glycopeptides 469:487 their glycopeptides 469:487 Mass spectrometry can be used to identify both the glycans of interest and the glycosylation sites to which those glycans are attached, when proteins are proteolytically digested and their glycopeptides are analyzed by a combination of high-resolution mass spectrometry (MS) and tandem mass spectrometry (MS/MS) methods. 27614974 10 6 theme MassList 1735:1742 arg1 software 1744:1751 the GlycoPep MassList software 1722:1751 the GlycoPep MassList software 1722:1751 When the GlycoPep MassList software was used to generate inclusion lists for LC-MS/MS experiments, more unique glycopeptides were selected for fragmentation. 27614974 1 7 theme growing 260:266 arg1 development 196:206 the development 192:206 the development of tools to study glycosylation 192:238 Protein glycosylation drives many biological processes and serves as markers for disease; therefore, the development of tools to study glycosylation is an essential and growing area of research. 27614974 1 7 theme growing 260:266 arg1 area 268:271 an essential and growing area 243:271 an essential and growing area of research 243:283 Protein glycosylation drives many biological processes and serves as markers for disease; therefore, the development of tools to study glycosylation is an essential and growing area of research. 27614974 2 8 dep spectrometry 543:554 arg1 methods 598:604 methods 598:604 methods 598:604 Mass spectrometry can be used to identify both the glycans of interest and the glycosylation sites to which those glycans are attached, when proteins are proteolytically digested and their glycopeptides are analyzed by a combination of high-resolution mass spectrometry (MS) and tandem mass spectrometry (MS/MS) methods. 27614974 12 9 theme list 2090:2093 arg1 usage 2068:2072 usage 2068:2072 usage of an inclusion list 2068:2093 In cases where background ions from proteins or other interferents are high, usage of an inclusion list is even more advantageous. 27614974 11 10 theme low 1975:1977 arg1 background 1979:1988 low background 1975:1988 low background 1975:1988 Generally, ∼30 % more unique glycopeptides can be analyzed per protein, in the simplest cases, with low background. 27614974 10 11 used used 1757:1760 arg2 software 1744:1751 the GlycoPep MassList software 1722:1751 the GlycoPep MassList software 1722:1751 When the GlycoPep MassList software was used to generate inclusion lists for LC-MS/MS experiments, more unique glycopeptides were selected for fragmentation. 27614974 4 12 theme MS/MS 822:826 arg1 data 828:831 MS/MS data 822:831 MS/MS data on these species 822:848 The digested glycopeptides are often present in complex mixtures and in low abundance, and the most commonly used approach to collect MS/MS data on these species is data-dependent acquisition (DDA), where only the most intense precursor ions trigger MS/MS. 27614974 2 13 theme spectrometry 543:554 arg1 combination 507:517 a combination 505:517 a combination of high-resolution mass spectrometry (MS) and tandem mass spectrometry (MS/MS) methods 505:604 Mass spectrometry can be used to identify both the glycans of interest and the glycosylation sites to which those glycans are attached, when proteins are proteolytically digested and their glycopeptides are analyzed by a combination of high-resolution mass spectrometry (MS) and tandem mass spectrometry (MS/MS) methods. 27614974 1 14 theme Protein 91:97 arg1 markers 160:166 markers 160:166 markers for disease 160:178 Protein glycosylation drives many biological processes and serves as markers for disease; therefore, the development of tools to study glycosylation is an essential and growing area of research. 27614974 1 14 theme Protein 91:97 arg1 glycosylation 99:111 Protein glycosylation 91:111 Protein glycosylation 91:111 Protein glycosylation drives many biological processes and serves as markers for disease; therefore, the development of tools to study glycosylation is an essential and growing area of research. 27614974 2 15 theme Mass 286:289 arg1 spectrometry 291:302 Mass spectrometry 286:302 Mass spectrometry 286:302 Mass spectrometry can be used to identify both the glycans of interest and the glycosylation sites to which those glycans are attached, when proteins are proteolytically digested and their glycopeptides are analyzed by a combination of high-resolution mass spectrometry (MS) and tandem mass spectrometry (MS/MS) methods. 27614974 14 16 gly glycopeptides 2220:2232 arg2 glycopeptides 2220:2232 glycopeptides 2220:2232 glycopeptides that get selected for MS/MS analysis 2220:2269 Graphical abstract Software increases the number of glycopeptides that get selected for MS/MS analysis. 27614974 2 17 theme high-resolution 522:536 arg1 MS 557:558 MS 557:558 MS 557:558 Mass spectrometry can be used to identify both the glycans of interest and the glycosylation sites to which those glycans are attached, when proteins are proteolytically digested and their glycopeptides are analyzed by a combination of high-resolution mass spectrometry (MS) and tandem mass spectrometry (MS/MS) methods. 27614974 2 17 theme high-resolution 522:536 arg1 spectrometry 543:554 high-resolution mass spectrometry 522:554 high-resolution mass spectrometry (MS) 522:559 Mass spectrometry can be used to identify both the glycans of interest and the glycosylation sites to which those glycans are attached, when proteins are proteolytically digested and their glycopeptides are analyzed by a combination of high-resolution mass spectrometry (MS) and tandem mass spectrometry (MS/MS) methods. 27614974 8 18 theme tandem-mass 1394:1404 arg1 LC-MS/MS 1420:1427 LC-MS/MS 1420:1427 LC-MS/MS 1420:1427 To solve this problem, we developed the software tool GlycoPep MassList, which can be used to generate inclusion lists for liquid chromatography tandem-mass spectrometry (LC-MS/MS) experiments. 27614974 8 18 theme tandem-mass 1394:1404 arg1 spectrometry 1406:1417 liquid chromatography tandem-mass spectrometry 1372:1417 liquid chromatography tandem-mass spectrometry (LC-MS/MS) experiments 1372:1440 To solve this problem, we developed the software tool GlycoPep MassList, which can be used to generate inclusion lists for liquid chromatography tandem-mass spectrometry (LC-MS/MS) experiments. 27614974 4 19 gly glycopeptides 701:713 arg2 glycopeptides 701:713 The digested glycopeptides 688:713 The digested glycopeptides 688:713 The digested glycopeptides are often present in complex mixtures and in low abundance, and the most commonly used approach to collect MS/MS data on these species is data-dependent acquisition (DDA), where only the most intense precursor ions trigger MS/MS. 27614974 4 19 gly glycopeptides 701:713 arg2 present 725:731 present 725:731 present 725:731 The digested glycopeptides are often present in complex mixtures and in low abundance, and the most commonly used approach to collect MS/MS data on these species is data-dependent acquisition (DDA), where only the most intense precursor ions trigger MS/MS. 27614974 1 20 theme tools 211:215 arg1 development 196:206 the development 192:206 the development of tools to study glycosylation 192:238 Protein glycosylation drives many biological processes and serves as markers for disease; therefore, the development of tools to study glycosylation is an essential and growing area of research. 27614974 1 20 theme tools 211:215 arg1 area 268:271 an essential and growing area 243:271 an essential and growing area of research 243:283 Protein glycosylation drives many biological processes and serves as markers for disease; therefore, the development of tools to study glycosylation is an essential and growing area of research. 27614974 4 21 theme data-dependent 853:866 arg1 acquisition 868:878 data-dependent acquisition 853:878 data-dependent acquisition (DDA) 853:884 The digested glycopeptides are often present in complex mixtures and in low abundance, and the most commonly used approach to collect MS/MS data on these species is data-dependent acquisition (DDA), where only the most intense precursor ions trigger MS/MS. 27614974 4 21 theme data-dependent 853:866 arg1 approach 802:809 the most commonly used approach 779:809 the most commonly used approach to collect MS/MS data on these species 779:848 The digested glycopeptides are often present in complex mixtures and in low abundance, and the most commonly used approach to collect MS/MS data on these species is data-dependent acquisition (DDA), where only the most intense precursor ions trigger MS/MS. 27614974 4 21 theme data-dependent 853:866 arg1 DDA 881:883 DDA 881:883 DDA 881:883 The digested glycopeptides are often present in complex mixtures and in low abundance, and the most commonly used approach to collect MS/MS data on these species is data-dependent acquisition (DDA), where only the most intense precursor ions trigger MS/MS. 27614974 9 22 dep semi-targeted 1516:1528 arg1 experiments 1569:1579 experiments 1569:1579 experiments 1569:1579 The utility of the software was tested by conducting comparisons between semi-targeted and untargeted data-dependent analysis experiments on a variety of proteins, including IgG, a protein whose glycosylation must be characterized during its production as a biotherapeutic. 27614974 4 23 attach present 725:731 arg2 glycopeptides 701:713 The digested glycopeptides 688:713 The digested glycopeptides 688:713 The digested glycopeptides are often present in complex mixtures and in low abundance, and the most commonly used approach to collect MS/MS data on these species is data-dependent acquisition (DDA), where only the most intense precursor ions trigger MS/MS. 27614974 4 23 attach present 725:731 arg1 mixtures 744:751 complex mixtures 736:751 complex mixtures 736:751 The digested glycopeptides are often present in complex mixtures and in low abundance, and the most commonly used approach to collect MS/MS data on these species is data-dependent acquisition (DDA), where only the most intense precursor ions trigger MS/MS. 27614974 4 23 attach present 725:731 arg1 abundance 764:772 low abundance 760:772 low abundance 760:772 The digested glycopeptides are often present in complex mixtures and in low abundance, and the most commonly used approach to collect MS/MS data on these species is data-dependent acquisition (DDA), where only the most intense precursor ions trigger MS/MS. 27614974 4 23 attach present 725:731 arg2 present 725:731 present 725:731 present 725:731 The digested glycopeptides are often present in complex mixtures and in low abundance, and the most commonly used approach to collect MS/MS data on these species is data-dependent acquisition (DDA), where only the most intense precursor ions trigger MS/MS. 27614974 10 24 theme inclusion 1774:1782 arg1 lists 1784:1788 inclusion lists 1774:1788 inclusion lists for LC-MS/MS experiments 1774:1813 When the GlycoPep MassList software was used to generate inclusion lists for LC-MS/MS experiments, more unique glycopeptides were selected for fragmentation. 27614974 12 25 from interferents 2045:2056 arg1 ions 2017:2020 background ions 2006:2020 background ions from proteins or other interferents 2006:2056 In cases where background ions from proteins or other interferents are high, usage of an inclusion list is even more advantageous. 27614974 1 26 theme biological 125:134 arg1 processes 136:144 many biological processes 120:144 many biological processes 120:144 Protein glycosylation drives many biological processes and serves as markers for disease; therefore, the development of tools to study glycosylation is an essential and growing area of research. 27614974 9 27 theme software 1462:1469 arg1 utility 1447:1453 The utility 1443:1453 The utility of the software 1443:1469 The utility of the software was tested by conducting comparisons between semi-targeted and untargeted data-dependent analysis experiments on a variety of proteins, including IgG, a protein whose glycosylation must be characterized during its production as a biotherapeutic. 27614974 11 28 theme simplest 1954:1961 arg1 cases 1963:1967 the simplest cases 1950:1967 the simplest cases 1950:1967 Generally, ∼30 % more unique glycopeptides can be analyzed per protein, in the simplest cases, with low background. 27614974 4 29 from abundance 764:772 arg1 present 725:731 present 725:731 present 725:731 The digested glycopeptides are often present in complex mixtures and in low abundance, and the most commonly used approach to collect MS/MS data on these species is data-dependent acquisition (DDA), where only the most intense precursor ions trigger MS/MS. 27614974 14 30 theme Graphical 2168:2176 arg1 Software 2187:2194 Graphical abstract Software 2168:2194 Graphical abstract Software 2168:2194 Graphical abstract Software increases the number of glycopeptides that get selected for MS/MS analysis. 27614974 0 31 theme glycopeptide 68:79 arg1 analyses 81:88 glycopeptide analyses 68:88 glycopeptide analyses 68:88 GlycoPep MassList: software to generate massive inclusion lists for glycopeptide analyses. 27614974 11 32 gly glycopeptides 1904:1916 arg2 glycopeptides 1904:1916 ∼30 % more unique glycopeptides 1886:1916 ∼30 % more unique glycopeptides 1886:1916 Generally, ∼30 % more unique glycopeptides can be analyzed per protein, in the simplest cases, with low background. 27614974 8 33 theme tool 1298:1301 arg1 MassList 1312:1319 the software tool GlycoPep MassList 1285:1319 the software tool GlycoPep MassList 1285:1319 To solve this problem, we developed the software tool GlycoPep MassList, which can be used to generate inclusion lists for liquid chromatography tandem-mass spectrometry (LC-MS/MS) experiments. 27614974 4 34 from mixtures 744:751 arg1 present 725:731 present 725:731 present 725:731 The digested glycopeptides are often present in complex mixtures and in low abundance, and the most commonly used approach to collect MS/MS data on these species is data-dependent acquisition (DDA), where only the most intense precursor ions trigger MS/MS. 27614974 4 34 from mixtures 744:751 arg1 glycopeptides 701:713 The digested glycopeptides 688:713 The digested glycopeptides 688:713 The digested glycopeptides are often present in complex mixtures and in low abundance, and the most commonly used approach to collect MS/MS data on these species is data-dependent acquisition (DDA), where only the most intense precursor ions trigger MS/MS. 27614974 4 35 theme intense 907:913 arg1 ions 925:928 only the most intense precursor ions 893:928 only the most intense precursor ions 893:928 The digested glycopeptides are often present in complex mixtures and in low abundance, and the most commonly used approach to collect MS/MS data on these species is data-dependent acquisition (DDA), where only the most intense precursor ions trigger MS/MS. 27614974 2 36 gly glycosylation 365:377 arg2 interest 348:355 interest 348:355 interest 348:355 Mass spectrometry can be used to identify both the glycans of interest and the glycosylation sites to which those glycans are attached, when proteins are proteolytically digested and their glycopeptides are analyzed by a combination of high-resolution mass spectrometry (MS) and tandem mass spectrometry (MS/MS) methods. 27614974 2 36 gly glycosylation 365:377 arg2 sites 379:383 the glycosylation sites 361:383 the glycosylation sites to which those glycans are attached, when proteins are proteolytically digested and their glycopeptides are analyzed by a combination of high-resolution mass spectrometry (MS) and tandem mass spectrometry (MS/MS) methods 361:604 Mass spectrometry can be used to identify both the glycans of interest and the glycosylation sites to which those glycans are attached, when proteins are proteolytically digested and their glycopeptides are analyzed by a combination of high-resolution mass spectrometry (MS) and tandem mass spectrometry (MS/MS) methods. 27614974 2 36 gly glycosylation 365:377 arg1 interest 348:355 interest 348:355 interest 348:355 Mass spectrometry can be used to identify both the glycans of interest and the glycosylation sites to which those glycans are attached, when proteins are proteolytically digested and their glycopeptides are analyzed by a combination of high-resolution mass spectrometry (MS) and tandem mass spectrometry (MS/MS) methods. 27614974 14 37 theme MS/MS 2256:2260 arg1 analysis 2262:2269 MS/MS analysis 2256:2269 MS/MS analysis 2256:2269 Graphical abstract Software increases the number of glycopeptides that get selected for MS/MS analysis. 27614974 11 38 theme more 1892:1895 arg1 glycopeptides 1904:1916 ∼30 % more unique glycopeptides 1886:1916 ∼30 % more unique glycopeptides 1886:1916 Generally, ∼30 % more unique glycopeptides can be analyzed per protein, in the simplest cases, with low background. 27614974 6 39 theme experimental 1040:1051 arg1 acquisition 1010:1020 Semi-targeted data acquisition 991:1020 Semi-targeted data acquisition 991:1020 Semi-targeted data acquisition is an alternative experimental approach that can alleviate this difficulty. 27614974 6 39 theme experimental 1040:1051 arg1 approach 1053:1060 an alternative experimental approach 1025:1060 an alternative experimental approach that can alleviate this difficulty 1025:1095 Semi-targeted data acquisition is an alternative experimental approach that can alleviate this difficulty. 27614974 5 40 gly glycopeptide 968:979 arg2 glycopeptide 968:979 limited glycopeptide coverage 960:988 limited glycopeptide coverage 960:988 DDA results in limited glycopeptide coverage. 27614974 0 41 theme GlycoPep 0:7 arg1 MassList 9:16 GlycoPep MassList 0:16 GlycoPep MassList: software to generate massive inclusion lists for glycopeptide analyses. 0:89 GlycoPep MassList: software to generate massive inclusion lists for glycopeptide analyses. 27614974 9 42 theme data-dependent 1545:1558 arg1 analysis 1560:1567 untargeted data-dependent analysis 1534:1567 untargeted data-dependent analysis 1534:1567 The utility of the software was tested by conducting comparisons between semi-targeted and untargeted data-dependent analysis experiments on a variety of proteins, including IgG, a protein whose glycosylation must be characterized during its production as a biotherapeutic. 27614974 4 43 dep approach 802:809 arg1 collect 814:820 collect 814:820 to collect MS/MS data on these species 811:848 The digested glycopeptides are often present in complex mixtures and in low abundance, and the most commonly used approach to collect MS/MS data on these species is data-dependent acquisition (DDA), where only the most intense precursor ions trigger MS/MS. 27614974 1 44 theme research 276:283 arg1 development 196:206 the development 192:206 the development of tools to study glycosylation 192:238 Protein glycosylation drives many biological processes and serves as markers for disease; therefore, the development of tools to study glycosylation is an essential and growing area of research. 27614974 1 44 theme research 276:283 arg1 area 268:271 an essential and growing area 243:271 an essential and growing area of research 243:283 Protein glycosylation drives many biological processes and serves as markers for disease; therefore, the development of tools to study glycosylation is an essential and growing area of research. 27614974 7 45 theme massive 1118:1124 arg1 heterogeneity 1126:1138 the massive heterogeneity 1114:1138 the massive heterogeneity of glycopeptides 1114:1155 However, due to the massive heterogeneity of glycopeptides, it is not obvious how to expediently generate inclusion lists for these types of analyses. 27614974 5 46 theme glycopeptide 968:979 arg1 coverage 981:988 limited glycopeptide coverage 960:988 limited glycopeptide coverage 960:988 DDA results in limited glycopeptide coverage. 27614974 6 47 theme Semi-targeted 991:1003 arg1 acquisition 1010:1020 Semi-targeted data acquisition 991:1020 Semi-targeted data acquisition 991:1020 Semi-targeted data acquisition is an alternative experimental approach that can alleviate this difficulty. 27614974 6 47 theme Semi-targeted 991:1003 arg1 approach 1053:1060 an alternative experimental approach 1025:1060 an alternative experimental approach that can alleviate this difficulty 1025:1095 Semi-targeted data acquisition is an alternative experimental approach that can alleviate this difficulty. 27614974 3 48 theme major 611:615 arg1 challenge 617:625 One major challenge 607:625 One major challenge in these experiments 607:646 One major challenge in these experiments is collecting the requisite MS/MS data. 27614974 8 49 theme inclusion 1352:1360 arg1 lists 1362:1366 inclusion lists 1352:1366 inclusion lists for liquid chromatography tandem-mass spectrometry (LC-MS/MS) experiments 1352:1440 To solve this problem, we developed the software tool GlycoPep MassList, which can be used to generate inclusion lists for liquid chromatography tandem-mass spectrometry (LC-MS/MS) experiments. 27614974 0 50 theme massive 40:46 arg1 lists 58:62 massive inclusion lists 40:62 massive inclusion lists for glycopeptide analyses 40:88 GlycoPep MassList: software to generate massive inclusion lists for glycopeptide analyses. 27614974 8 51 used used 1335:1338 arg2 MassList 1312:1319 the software tool GlycoPep MassList 1285:1319 the software tool GlycoPep MassList 1285:1319 To solve this problem, we developed the software tool GlycoPep MassList, which can be used to generate inclusion lists for liquid chromatography tandem-mass spectrometry (LC-MS/MS) experiments. 27614974 8 52 theme chromatography 1379:1392 arg1 LC-MS/MS 1420:1427 LC-MS/MS 1420:1427 LC-MS/MS 1420:1427 To solve this problem, we developed the software tool GlycoPep MassList, which can be used to generate inclusion lists for liquid chromatography tandem-mass spectrometry (LC-MS/MS) experiments. 27614974 8 52 theme chromatography 1379:1392 arg1 spectrometry 1406:1417 liquid chromatography tandem-mass spectrometry 1372:1417 liquid chromatography tandem-mass spectrometry (LC-MS/MS) experiments 1372:1440 To solve this problem, we developed the software tool GlycoPep MassList, which can be used to generate inclusion lists for liquid chromatography tandem-mass spectrometry (LC-MS/MS) experiments. 27614974 2 53 theme interest 348:355 arg1 glycans 337:343 the glycans 333:343 the glycans of interest 333:355 Mass spectrometry can be used to identify both the glycans of interest and the glycosylation sites to which those glycans are attached, when proteins are proteolytically digested and their glycopeptides are analyzed by a combination of high-resolution mass spectrometry (MS) and tandem mass spectrometry (MS/MS) methods. 27614974 2 53 theme interest 348:355 arg1 sites 379:383 the glycosylation sites 361:383 the glycosylation sites to which those glycans are attached, when proteins are proteolytically digested and their glycopeptides are analyzed by a combination of high-resolution mass spectrometry (MS) and tandem mass spectrometry (MS/MS) methods 361:604 Mass spectrometry can be used to identify both the glycans of interest and the glycosylation sites to which those glycans are attached, when proteins are proteolytically digested and their glycopeptides are analyzed by a combination of high-resolution mass spectrometry (MS) and tandem mass spectrometry (MS/MS) methods. 27614974 2 53 theme interest 348:355 arg1 interest 348:355 interest 348:355 interest 348:355 Mass spectrometry can be used to identify both the glycans of interest and the glycosylation sites to which those glycans are attached, when proteins are proteolytically digested and their glycopeptides are analyzed by a combination of high-resolution mass spectrometry (MS) and tandem mass spectrometry (MS/MS) methods. 27614974 12 54 from cases 1994:1998 arg1 advantageous 2108:2119 advantageous 2108:2119 advantageous 2108:2119 In cases where background ions from proteins or other interferents are high, usage of an inclusion list is even more advantageous. 27614974 2 55 theme spectrometry 577:588 arg1 combination 507:517 a combination 505:517 a combination of high-resolution mass spectrometry (MS) and tandem mass spectrometry (MS/MS) methods 505:604 Mass spectrometry can be used to identify both the glycans of interest and the glycosylation sites to which those glycans are attached, when proteins are proteolytically digested and their glycopeptides are analyzed by a combination of high-resolution mass spectrometry (MS) and tandem mass spectrometry (MS/MS) methods. 27614974 14 56 theme abstract 2178:2185 arg1 Software 2187:2194 Graphical abstract Software 2168:2194 Graphical abstract Software 2168:2194 Graphical abstract Software increases the number of glycopeptides that get selected for MS/MS analysis. 27614974 3 57 theme requisite 666:674 arg1 data 682:685 the requisite MS/MS data 662:685 the requisite MS/MS data 662:685 One major challenge in these experiments is collecting the requisite MS/MS data. 27614974 4 58 theme used 797:800 arg1 acquisition 868:878 data-dependent acquisition 853:878 data-dependent acquisition (DDA) 853:884 The digested glycopeptides are often present in complex mixtures and in low abundance, and the most commonly used approach to collect MS/MS data on these species is data-dependent acquisition (DDA), where only the most intense precursor ions trigger MS/MS. 27614974 4 58 theme used 797:800 arg1 approach 802:809 the most commonly used approach 779:809 the most commonly used approach to collect MS/MS data on these species 779:848 The digested glycopeptides are often present in complex mixtures and in low abundance, and the most commonly used approach to collect MS/MS data on these species is data-dependent acquisition (DDA), where only the most intense precursor ions trigger MS/MS. 27614974 2 59 theme tandem 565:570 arg1 spectrometry 577:588 tandem mass spectrometry 565:588 tandem mass spectrometry (MS/MS) 565:596 Mass spectrometry can be used to identify both the glycans of interest and the glycosylation sites to which those glycans are attached, when proteins are proteolytically digested and their glycopeptides are analyzed by a combination of high-resolution mass spectrometry (MS) and tandem mass spectrometry (MS/MS) methods. 27614974 2 59 theme tandem 565:570 arg1 MS/MS 591:595 MS/MS 591:595 MS/MS 591:595 Mass spectrometry can be used to identify both the glycans of interest and the glycosylation sites to which those glycans are attached, when proteins are proteolytically digested and their glycopeptides are analyzed by a combination of high-resolution mass spectrometry (MS) and tandem mass spectrometry (MS/MS) methods. 27614974 3 60 from challenge 617:625 arg1 experiments 636:646 these experiments 630:646 these experiments 630:646 One major challenge in these experiments is collecting the requisite MS/MS data. 27614974 10 61 theme GlycoPep 1726:1733 arg1 software 1744:1751 the GlycoPep MassList software 1722:1751 the GlycoPep MassList software 1722:1751 When the GlycoPep MassList software was used to generate inclusion lists for LC-MS/MS experiments, more unique glycopeptides were selected for fragmentation. 27614974 12 62 theme inclusion 2080:2088 arg1 list 2090:2093 an inclusion list 2077:2093 an inclusion list 2077:2093 In cases where background ions from proteins or other interferents are high, usage of an inclusion list is even more advantageous. 27614974 2 63 theme mass 538:541 arg1 MS 557:558 MS 557:558 MS 557:558 Mass spectrometry can be used to identify both the glycans of interest and the glycosylation sites to which those glycans are attached, when proteins are proteolytically digested and their glycopeptides are analyzed by a combination of high-resolution mass spectrometry (MS) and tandem mass spectrometry (MS/MS) methods. 27614974 2 63 theme mass 538:541 arg1 spectrometry 543:554 high-resolution mass spectrometry 522:554 high-resolution mass spectrometry (MS) 522:559 Mass spectrometry can be used to identify both the glycans of interest and the glycosylation sites to which those glycans are attached, when proteins are proteolytically digested and their glycopeptides are analyzed by a combination of high-resolution mass spectrometry (MS) and tandem mass spectrometry (MS/MS) methods. 27614974 8 64 theme spectrometry 1406:1417 arg1 experiments 1430:1440 liquid chromatography tandem-mass spectrometry (LC-MS/MS) experiments 1372:1440 liquid chromatography tandem-mass spectrometry (LC-MS/MS) experiments 1372:1440 To solve this problem, we developed the software tool GlycoPep MassList, which can be used to generate inclusion lists for liquid chromatography tandem-mass spectrometry (LC-MS/MS) experiments. 27614974 10 65 theme LC-MS/MS 1794:1801 arg1 experiments 1803:1813 LC-MS/MS experiments 1794:1813 LC-MS/MS experiments 1794:1813 When the GlycoPep MassList software was used to generate inclusion lists for LC-MS/MS experiments, more unique glycopeptides were selected for fragmentation. 27614974 10 66 gly glycopeptides 1828:1840 arg2 glycopeptides 1828:1840 more unique glycopeptides 1816:1840 more unique glycopeptides 1816:1840 When the GlycoPep MassList software was used to generate inclusion lists for LC-MS/MS experiments, more unique glycopeptides were selected for fragmentation. 27614974 1 67 theme many 120:123 arg1 processes 136:144 many biological processes 120:144 many biological processes 120:144 Protein glycosylation drives many biological processes and serves as markers for disease; therefore, the development of tools to study glycosylation is an essential and growing area of research. 27614974 4 68 from data 828:831 arg1 species 842:848 these species 836:848 these species 836:848 The digested glycopeptides are often present in complex mixtures and in low abundance, and the most commonly used approach to collect MS/MS data on these species is data-dependent acquisition (DDA), where only the most intense precursor ions trigger MS/MS. 27614974 12 69 theme other 2039:2043 arg1 interferents 2045:2056 other interferents 2039:2056 other interferents 2039:2056 In cases where background ions from proteins or other interferents are high, usage of an inclusion list is even more advantageous. 27614974 10 70 theme unique 1821:1826 arg1 glycopeptides 1828:1840 more unique glycopeptides 1816:1840 more unique glycopeptides 1816:1840 When the GlycoPep MassList software was used to generate inclusion lists for LC-MS/MS experiments, more unique glycopeptides were selected for fragmentation. 27614974 4 71 theme digested 692:699 arg1 present 725:731 present 725:731 present 725:731 The digested glycopeptides are often present in complex mixtures and in low abundance, and the most commonly used approach to collect MS/MS data on these species is data-dependent acquisition (DDA), where only the most intense precursor ions trigger MS/MS. 27614974 4 71 theme digested 692:699 arg1 glycopeptides 701:713 The digested glycopeptides 688:713 The digested glycopeptides 688:713 The digested glycopeptides are often present in complex mixtures and in low abundance, and the most commonly used approach to collect MS/MS data on these species is data-dependent acquisition (DDA), where only the most intense precursor ions trigger MS/MS. 27614974 12 72 from proteins 2027:2034 arg1 ions 2017:2020 background ions 2006:2020 background ions from proteins or other interferents 2006:2056 In cases where background ions from proteins or other interferents are high, usage of an inclusion list is even more advantageous. 27614974 4 73 theme precursor 915:923 arg1 ions 925:928 only the most intense precursor ions 893:928 only the most intense precursor ions 893:928 The digested glycopeptides are often present in complex mixtures and in low abundance, and the most commonly used approach to collect MS/MS data on these species is data-dependent acquisition (DDA), where only the most intense precursor ions trigger MS/MS. 27614974 4 74 theme low 760:762 arg1 abundance 764:772 low abundance 760:772 low abundance 760:772 The digested glycopeptides are often present in complex mixtures and in low abundance, and the most commonly used approach to collect MS/MS data on these species is data-dependent acquisition (DDA), where only the most intense precursor ions trigger MS/MS. 27614974 8 75 theme software 1289:1296 arg1 MassList 1312:1319 the software tool GlycoPep MassList 1285:1319 the software tool GlycoPep MassList 1285:1319 To solve this problem, we developed the software tool GlycoPep MassList, which can be used to generate inclusion lists for liquid chromatography tandem-mass spectrometry (LC-MS/MS) experiments. 27614974 4 76 theme complex 736:742 arg1 mixtures 744:751 complex mixtures 736:751 complex mixtures 736:751 The digested glycopeptides are often present in complex mixtures and in low abundance, and the most commonly used approach to collect MS/MS data on these species is data-dependent acquisition (DDA), where only the most intense precursor ions trigger MS/MS. 27614974 0 77 gly glycopeptide 68:79 arg2 glycopeptide 68:79 glycopeptide 68:79 glycopeptide 68:79 GlycoPep MassList: software to generate massive inclusion lists for glycopeptide analyses. 27614974 4 78 theme most 902:905 arg1 ions 925:928 only the most intense precursor ions 893:928 only the most intense precursor ions 893:928 The digested glycopeptides are often present in complex mixtures and in low abundance, and the most commonly used approach to collect MS/MS data on these species is data-dependent acquisition (DDA), where only the most intense precursor ions trigger MS/MS. 27614974 2 79 used used 311:314 arg2 spectrometry 291:302 Mass spectrometry 286:302 Mass spectrometry 286:302 Mass spectrometry can be used to identify both the glycans of interest and the glycosylation sites to which those glycans are attached, when proteins are proteolytically digested and their glycopeptides are analyzed by a combination of high-resolution mass spectrometry (MS) and tandem mass spectrometry (MS/MS) methods. 27614974 8 80 theme GlycoPep 1303:1310 arg1 MassList 1312:1319 the software tool GlycoPep MassList 1285:1319 the software tool GlycoPep MassList 1285:1319 To solve this problem, we developed the software tool GlycoPep MassList, which can be used to generate inclusion lists for liquid chromatography tandem-mass spectrometry (LC-MS/MS) experiments. 27614974 2 81 theme glycosylation 365:377 arg1 sites 379:383 the glycosylation sites 361:383 the glycosylation sites to which those glycans are attached, when proteins are proteolytically digested and their glycopeptides are analyzed by a combination of high-resolution mass spectrometry (MS) and tandem mass spectrometry (MS/MS) methods 361:604 Mass spectrometry can be used to identify both the glycans of interest and the glycosylation sites to which those glycans are attached, when proteins are proteolytically digested and their glycopeptides are analyzed by a combination of high-resolution mass spectrometry (MS) and tandem mass spectrometry (MS/MS) methods. 27614974 2 81 theme glycosylation 365:377 arg1 interest 348:355 interest 348:355 interest 348:355 Mass spectrometry can be used to identify both the glycans of interest and the glycosylation sites to which those glycans are attached, when proteins are proteolytically digested and their glycopeptides are analyzed by a combination of high-resolution mass spectrometry (MS) and tandem mass spectrometry (MS/MS) methods. 27614974 7 82 theme glycopeptides 1143:1155 arg1 heterogeneity 1126:1138 the massive heterogeneity 1114:1138 the massive heterogeneity of glycopeptides 1114:1155 However, due to the massive heterogeneity of glycopeptides, it is not obvious how to expediently generate inclusion lists for these types of analyses. 27614974 4 83 from present 725:731 arg1 mixtures 744:751 complex mixtures 736:751 complex mixtures 736:751 The digested glycopeptides are often present in complex mixtures and in low abundance, and the most commonly used approach to collect MS/MS data on these species is data-dependent acquisition (DDA), where only the most intense precursor ions trigger MS/MS. 27614974 4 83 from present 725:731 arg1 abundance 764:772 low abundance 760:772 low abundance 760:772 The digested glycopeptides are often present in complex mixtures and in low abundance, and the most commonly used approach to collect MS/MS data on these species is data-dependent acquisition (DDA), where only the most intense precursor ions trigger MS/MS. 27614974 9 84 theme untargeted 1534:1543 arg1 analysis 1560:1567 untargeted data-dependent analysis 1534:1567 untargeted data-dependent analysis 1534:1567 The utility of the software was tested by conducting comparisons between semi-targeted and untargeted data-dependent analysis experiments on a variety of proteins, including IgG, a protein whose glycosylation must be characterized during its production as a biotherapeutic. 27614974 6 85 theme alternative 1028:1038 arg1 acquisition 1010:1020 Semi-targeted data acquisition 991:1020 Semi-targeted data acquisition 991:1020 Semi-targeted data acquisition is an alternative experimental approach that can alleviate this difficulty. 27614974 6 85 theme alternative 1028:1038 arg1 approach 1053:1060 an alternative experimental approach 1025:1060 an alternative experimental approach that can alleviate this difficulty 1025:1095 Semi-targeted data acquisition is an alternative experimental approach that can alleviate this difficulty. 27614974 2 86 attach attached 412:419 arg2 glycans 400:406 those glycans 394:406 those glycans 394:406 Mass spectrometry can be used to identify both the glycans of interest and the glycosylation sites to which those glycans are attached, when proteins are proteolytically digested and their glycopeptides are analyzed by a combination of high-resolution mass spectrometry (MS) and tandem mass spectrometry (MS/MS) methods. 27614974 2 86 attach attached 412:419 arg1 sites 379:383 the glycosylation sites 361:383 the glycosylation sites to which those glycans are attached, when proteins are proteolytically digested and their glycopeptides are analyzed by a combination of high-resolution mass spectrometry (MS) and tandem mass spectrometry (MS/MS) methods 361:604 Mass spectrometry can be used to identify both the glycans of interest and the glycosylation sites to which those glycans are attached, when proteins are proteolytically digested and their glycopeptides are analyzed by a combination of high-resolution mass spectrometry (MS) and tandem mass spectrometry (MS/MS) methods. 27614974 2 86 attach attached 412:419 arg1 interest 348:355 interest 348:355 interest 348:355 Mass spectrometry can be used to identify both the glycans of interest and the glycosylation sites to which those glycans are attached, when proteins are proteolytically digested and their glycopeptides are analyzed by a combination of high-resolution mass spectrometry (MS) and tandem mass spectrometry (MS/MS) methods. 27614974 14 87 theme glycopeptides 2220:2232 arg1 number 2210:2215 the number 2206:2215 the number of glycopeptides that get selected for MS/MS analysis 2206:2269 Graphical abstract Software increases the number of glycopeptides that get selected for MS/MS analysis. 27614974 5 88 theme limited 960:966 arg1 coverage 981:988 limited glycopeptide coverage 960:988 limited glycopeptide coverage 960:988 DDA results in limited glycopeptide coverage. 27614974 6 89 theme data 1005:1008 arg1 acquisition 1010:1020 Semi-targeted data acquisition 991:1020 Semi-targeted data acquisition 991:1020 Semi-targeted data acquisition is an alternative experimental approach that can alleviate this difficulty. 27614974 6 89 theme data 1005:1008 arg1 approach 1053:1060 an alternative experimental approach 1025:1060 an alternative experimental approach that can alleviate this difficulty 1025:1095 Semi-targeted data acquisition is an alternative experimental approach that can alleviate this difficulty. 27614974 0 90 theme inclusion 48:56 arg1 lists 58:62 massive inclusion lists 40:62 massive inclusion lists for glycopeptide analyses 40:88 GlycoPep MassList: software to generate massive inclusion lists for glycopeptide analyses. 27614974 7 91 theme analyses 1239:1246 arg1 types 1230:1234 these types 1224:1234 these types of analyses 1224:1246 However, due to the massive heterogeneity of glycopeptides, it is not obvious how to expediently generate inclusion lists for these types of analyses. 27614974 4 92 located present 725:731 arg2 glycopeptides 701:713 The digested glycopeptides 688:713 The digested glycopeptides 688:713 The digested glycopeptides are often present in complex mixtures and in low abundance, and the most commonly used approach to collect MS/MS data on these species is data-dependent acquisition (DDA), where only the most intense precursor ions trigger MS/MS. 27614974 4 92 located present 725:731 arg1 mixtures 744:751 complex mixtures 736:751 complex mixtures 736:751 The digested glycopeptides are often present in complex mixtures and in low abundance, and the most commonly used approach to collect MS/MS data on these species is data-dependent acquisition (DDA), where only the most intense precursor ions trigger MS/MS. 27614974 4 92 located present 725:731 arg2 present 725:731 present 725:731 present 725:731 The digested glycopeptides are often present in complex mixtures and in low abundance, and the most commonly used approach to collect MS/MS data on these species is data-dependent acquisition (DDA), where only the most intense precursor ions trigger MS/MS. 27614974 7 93 gly heterogeneity 1126:1138 arg1 glycopeptides 1143:1155 glycopeptides 1143:1155 glycopeptides 1143:1155 However, due to the massive heterogeneity of glycopeptides, it is not obvious how to expediently generate inclusion lists for these types of analyses. 27614974 9 94 theme proteins 1597:1604 arg1 variety 1586:1592 a variety 1584:1592 a variety of proteins, including IgG, a protein whose glycosylation must be characterized during its production as a biotherapeutic 1584:1714 The utility of the software was tested by conducting comparisons between semi-targeted and untargeted data-dependent analysis experiments on a variety of proteins, including IgG, a protein whose glycosylation must be characterized during its production as a biotherapeutic. 27614974 9 94 theme proteins 1597:1604 arg1 proteins 1597:1604 proteins 1597:1604 proteins 1597:1604 The utility of the software was tested by conducting comparisons between semi-targeted and untargeted data-dependent analysis experiments on a variety of proteins, including IgG, a protein whose glycosylation must be characterized during its production as a biotherapeutic. 27614974 9 94 theme proteins 1597:1604 arg1 IgG 1617:1619 IgG 1617:1619 IgG 1617:1619 The utility of the software was tested by conducting comparisons between semi-targeted and untargeted data-dependent analysis experiments on a variety of proteins, including IgG, a protein whose glycosylation must be characterized during its production as a biotherapeutic. 27614974 7 95 gly glycopeptides 1143:1155 arg2 glycopeptides 1143:1155 glycopeptides 1143:1155 glycopeptides 1143:1155 However, due to the massive heterogeneity of glycopeptides, it is not obvious how to expediently generate inclusion lists for these types of analyses. 27614974 11 96 theme unique 1897:1902 arg1 glycopeptides 1904:1916 ∼30 % more unique glycopeptides 1886:1916 ∼30 % more unique glycopeptides 1886:1916 Generally, ∼30 % more unique glycopeptides can be analyzed per protein, in the simplest cases, with low background. 27614974 3 97 theme MS/MS 676:680 arg1 data 682:685 the requisite MS/MS data 662:685 the requisite MS/MS data 662:685 One major challenge in these experiments is collecting the requisite MS/MS data. 27614974 8 98 theme liquid 1372:1377 arg1 LC-MS/MS 1420:1427 LC-MS/MS 1420:1427 LC-MS/MS 1420:1427 To solve this problem, we developed the software tool GlycoPep MassList, which can be used to generate inclusion lists for liquid chromatography tandem-mass spectrometry (LC-MS/MS) experiments. 27614974 8 98 theme liquid 1372:1377 arg1 spectrometry 1406:1417 liquid chromatography tandem-mass spectrometry 1372:1417 liquid chromatography tandem-mass spectrometry (LC-MS/MS) experiments 1372:1440 To solve this problem, we developed the software tool GlycoPep MassList, which can be used to generate inclusion lists for liquid chromatography tandem-mass spectrometry (LC-MS/MS) experiments. 27587357 6 0 theme secretory 1490:1498 arg1 pathway 1500:1506 the yeast secretory pathway 1480:1506 the yeast secretory pathway 1480:1506 We conclude that the hut1+ gene product is involved in UDP-Glc entrance into the ER, but that at least another as yet unknown NST displaying an unconventional sequence operates in the yeast secretory pathway. 27587357 1 1 from sugar 262:266 arg1 residue 234:240 a Glc residue 228:240 a Glc residue from the nucleotide sugar (NS) 228:271 UDP-Glc entrance into the endoplasmic reticulum (ER) of eukaryotic cells is a key step in the quality control of glycoprotein folding, a mechanism requiring transfer of a Glc residue from the nucleotide sugar (NS) to glycoprotein folding intermediates by the UDP-Glc:glycoprotein glucosyltransferase (UGGT). 27587357 1 1 from sugar 262:266 arg1 transfer 216:223 transfer 216:223 transfer of a Glc residue from the nucleotide sugar (NS) to glycoprotein folding intermediates 216:309 UDP-Glc entrance into the endoplasmic reticulum (ER) of eukaryotic cells is a key step in the quality control of glycoprotein folding, a mechanism requiring transfer of a Glc residue from the nucleotide sugar (NS) to glycoprotein folding intermediates by the UDP-Glc:glycoprotein glucosyltransferase (UGGT). 27587357 1 2 theme cells 126:130 arg1 step 141:144 a key step 135:144 a key step in the quality control of glycoprotein folding 135:191 UDP-Glc entrance into the endoplasmic reticulum (ER) of eukaryotic cells is a key step in the quality control of glycoprotein folding, a mechanism requiring transfer of a Glc residue from the nucleotide sugar (NS) to glycoprotein folding intermediates by the UDP-Glc:glycoprotein glucosyltransferase (UGGT). 27587357 1 2 theme cells 126:130 arg1 entrance 67:74 UDP-Glc entrance 59:74 UDP-Glc entrance into the endoplasmic reticulum (ER) of eukaryotic cells 59:130 UDP-Glc entrance into the endoplasmic reticulum (ER) of eukaryotic cells is a key step in the quality control of glycoprotein folding, a mechanism requiring transfer of a Glc residue from the nucleotide sugar (NS) to glycoprotein folding intermediates by the UDP-Glc:glycoprotein glucosyltransferase (UGGT). 27587357 3 3 theme vrg4+ 693:697 arg1 genes 680:684 genes 680:684 genes gms1+, vrg4+, pet1+, pet2+ and pet3+ to the Golgi 680:734 The protein products of two of them (hut1+ and yea4+) localize to the ER, those of genes gms1+, vrg4+, pet1+, pet2+ and pet3+ to the Golgi, whereas that of gms2+ has an unknown location. 27587357 3 4 theme pet2+ 707:711 arg1 genes 680:684 genes 680:684 genes gms1+, vrg4+, pet1+, pet2+ and pet3+ to the Golgi 680:734 The protein products of two of them (hut1+ and yea4+) localize to the ER, those of genes gms1+, vrg4+, pet1+, pet2+ and pet3+ to the Golgi, whereas that of gms2+ has an unknown location. 27587357 3 5 theme two 621:623 arg1 products 609:616 The protein products 597:616 The protein products of two of them (hut1+ and yea4+) 597:649 The protein products of two of them (hut1+ and yea4+) localize to the ER, those of genes gms1+, vrg4+, pet1+, pet2+ and pet3+ to the Golgi, whereas that of gms2+ has an unknown location. 27587357 4 6 theme Δhut1Δyea4Δgms2 1015:1029 arg1 mutants 1031:1037 Δhut1Δyea4Δgms2 mutants 1015:1037 Δhut1Δyea4Δgms2 mutants 1015:1037 Here we demonstrate that (1) Δhut1 and Δgpt1 (UGGT null) mutants share several phenotypic features; (2) Δhut1 mutants show a 50% reduction in UDP-Glc transport into ER-derived membranes; (3) in vivo UDP-Glc ER entrance occurred in Δhut1Δyea4Δgms2 mutants and in cells in which Δhut1 disruption was combined with that of each of four of the genes encoding Golgi-located proteins. 27587357 5 7 contain have 1235:1238 arg2 location 1251:1258 an unknown location 1240:1258 an unknown location 1240:1258 Therefore, disruption of all genes whose products localize to the ER or have an unknown location did not obliterate UDP-Glc ER entrance. 27587357 5 7 contain have 1235:1238 arg1 products 1204:1211 products 1204:1211 products 1204:1211 Therefore, disruption of all genes whose products localize to the ER or have an unknown location did not obliterate UDP-Glc ER entrance. 27587357 1 8 theme glycoprotein 276:287 arg1 intermediates 297:309 glycoprotein folding intermediates 276:309 glycoprotein folding intermediates 276:309 UDP-Glc entrance into the endoplasmic reticulum (ER) of eukaryotic cells is a key step in the quality control of glycoprotein folding, a mechanism requiring transfer of a Glc residue from the nucleotide sugar (NS) to glycoprotein folding intermediates by the UDP-Glc:glycoprotein glucosyltransferase (UGGT). 27587357 2 9 theme nucleotide-sugar 527:542 arg1 transporters 544:555 all known nucleotide-sugar transporters 517:555 all known nucleotide-sugar transporters (NSTs) of the secretory pathway 517:587 According to a bioinformatics search there are only eight genes in the Schizosaccharomyces pombe genome belonging to the three Pfam families to which all known nucleotide-sugar transporters (NSTs) of the secretory pathway belong. 27587357 2 9 theme nucleotide-sugar 527:542 arg1 NSTs 558:561 NSTs 558:561 NSTs 558:561 According to a bioinformatics search there are only eight genes in the Schizosaccharomyces pombe genome belonging to the three Pfam families to which all known nucleotide-sugar transporters (NSTs) of the secretory pathway belong. 27587357 1 10 gly glycoprotein 172:183 arg1 glycoprotein 172:183 glycoprotein folding 172:191 glycoprotein folding 172:191 UDP-Glc entrance into the endoplasmic reticulum (ER) of eukaryotic cells is a key step in the quality control of glycoprotein folding, a mechanism requiring transfer of a Glc residue from the nucleotide sugar (NS) to glycoprotein folding intermediates by the UDP-Glc:glycoprotein glucosyltransferase (UGGT). 27587357 3 11 theme pet1+ 700:704 arg1 genes 680:684 genes 680:684 genes gms1+, vrg4+, pet1+, pet2+ and pet3+ to the Golgi 680:734 The protein products of two of them (hut1+ and yea4+) localize to the ER, those of genes gms1+, vrg4+, pet1+, pet2+ and pet3+ to the Golgi, whereas that of gms2+ has an unknown location. 27587357 7 12 theme UDP-Glc 1571:1577 arg1 entrance 1579:1586 UDP-Glc entrance 1571:1586 UDP-Glc entrance into the yeast ER 1571:1604 This conclusion agrees with our previous results showing that UDP-Glc entrance into the yeast ER does not follow the classical NST antiport mechanism. 27587357 1 13 theme folding 289:295 arg1 intermediates 297:309 glycoprotein folding intermediates 276:309 glycoprotein folding intermediates 276:309 UDP-Glc entrance into the endoplasmic reticulum (ER) of eukaryotic cells is a key step in the quality control of glycoprotein folding, a mechanism requiring transfer of a Glc residue from the nucleotide sugar (NS) to glycoprotein folding intermediates by the UDP-Glc:glycoprotein glucosyltransferase (UGGT). 27587357 2 14 theme known 521:525 arg1 transporters 544:555 all known nucleotide-sugar transporters 517:555 all known nucleotide-sugar transporters (NSTs) of the secretory pathway 517:587 According to a bioinformatics search there are only eight genes in the Schizosaccharomyces pombe genome belonging to the three Pfam families to which all known nucleotide-sugar transporters (NSTs) of the secretory pathway belong. 27587357 2 14 theme known 521:525 arg1 NSTs 558:561 NSTs 558:561 NSTs 558:561 According to a bioinformatics search there are only eight genes in the Schizosaccharomyces pombe genome belonging to the three Pfam families to which all known nucleotide-sugar transporters (NSTs) of the secretory pathway belong. 27587357 2 15 theme pathway 581:587 arg1 transporters 544:555 all known nucleotide-sugar transporters 517:555 all known nucleotide-sugar transporters (NSTs) of the secretory pathway 517:587 According to a bioinformatics search there are only eight genes in the Schizosaccharomyces pombe genome belonging to the three Pfam families to which all known nucleotide-sugar transporters (NSTs) of the secretory pathway belong. 27587357 2 15 theme pathway 581:587 arg1 NSTs 558:561 NSTs 558:561 NSTs 558:561 According to a bioinformatics search there are only eight genes in the Schizosaccharomyces pombe genome belonging to the three Pfam families to which all known nucleotide-sugar transporters (NSTs) of the secretory pathway belong. 27587357 4 16 theme UDP-Glc 926:932 arg1 transport 934:942 UDP-Glc transport 926:942 UDP-Glc transport into ER-derived membranes 926:968 Here we demonstrate that (1) Δhut1 and Δgpt1 (UGGT null) mutants share several phenotypic features; (2) Δhut1 mutants show a 50% reduction in UDP-Glc transport into ER-derived membranes; (3) in vivo UDP-Glc ER entrance occurred in Δhut1Δyea4Δgms2 mutants and in cells in which Δhut1 disruption was combined with that of each of four of the genes encoding Golgi-located proteins. 27587357 2 17 theme secretory 571:579 arg1 pathway 581:587 the secretory pathway 567:587 the secretory pathway 567:587 According to a bioinformatics search there are only eight genes in the Schizosaccharomyces pombe genome belonging to the three Pfam families to which all known nucleotide-sugar transporters (NSTs) of the secretory pathway belong. 27587357 3 18 theme unknown 766:772 arg1 location 774:781 an unknown location 763:781 an unknown location 763:781 The protein products of two of them (hut1+ and yea4+) localize to the ER, those of genes gms1+, vrg4+, pet1+, pet2+ and pet3+ to the Golgi, whereas that of gms2+ has an unknown location. 27587357 2 19 theme Schizosaccharomyces 438:456 arg1 genome 464:469 the Schizosaccharomyces pombe genome 434:469 the Schizosaccharomyces pombe genome belonging to the three Pfam families to which all known nucleotide-sugar transporters (NSTs) of the secretory pathway belong 434:594 According to a bioinformatics search there are only eight genes in the Schizosaccharomyces pombe genome belonging to the three Pfam families to which all known nucleotide-sugar transporters (NSTs) of the secretory pathway belong. 27587357 4 20 theme ER 991:992 arg1 entrance 994:1001 vivo UDP-Glc ER entrance 978:1001 vivo UDP-Glc ER entrance occurred in Δhut1Δyea4Δgms2 mutants and in cells in which Δhut1 disruption was combined with that of each of four of the genes encoding Golgi-located proteins 978:1160 Here we demonstrate that (1) Δhut1 and Δgpt1 (UGGT null) mutants share several phenotypic features; (2) Δhut1 mutants show a 50% reduction in UDP-Glc transport into ER-derived membranes; (3) in vivo UDP-Glc ER entrance occurred in Δhut1Δyea4Δgms2 mutants and in cells in which Δhut1 disruption was combined with that of each of four of the genes encoding Golgi-located proteins. 27587357 1 21 theme UDP-Glc 59:65 arg1 step 141:144 a key step 135:144 a key step in the quality control of glycoprotein folding 135:191 UDP-Glc entrance into the endoplasmic reticulum (ER) of eukaryotic cells is a key step in the quality control of glycoprotein folding, a mechanism requiring transfer of a Glc residue from the nucleotide sugar (NS) to glycoprotein folding intermediates by the UDP-Glc:glycoprotein glucosyltransferase (UGGT). 27587357 1 21 theme UDP-Glc 59:65 arg1 entrance 67:74 UDP-Glc entrance 59:74 UDP-Glc entrance into the endoplasmic reticulum (ER) of eukaryotic cells 59:130 UDP-Glc entrance into the endoplasmic reticulum (ER) of eukaryotic cells is a key step in the quality control of glycoprotein folding, a mechanism requiring transfer of a Glc residue from the nucleotide sugar (NS) to glycoprotein folding intermediates by the UDP-Glc:glycoprotein glucosyltransferase (UGGT). 27587357 1 22 gly glycoprotein 276:287 arg1 glycoprotein 276:287 glycoprotein folding intermediates 276:309 glycoprotein folding intermediates 276:309 UDP-Glc entrance into the endoplasmic reticulum (ER) of eukaryotic cells is a key step in the quality control of glycoprotein folding, a mechanism requiring transfer of a Glc residue from the nucleotide sugar (NS) to glycoprotein folding intermediates by the UDP-Glc:glycoprotein glucosyltransferase (UGGT). 27587357 1 23 theme key 137:139 arg1 step 141:144 a key step 135:144 a key step in the quality control of glycoprotein folding 135:191 UDP-Glc entrance into the endoplasmic reticulum (ER) of eukaryotic cells is a key step in the quality control of glycoprotein folding, a mechanism requiring transfer of a Glc residue from the nucleotide sugar (NS) to glycoprotein folding intermediates by the UDP-Glc:glycoprotein glucosyltransferase (UGGT). 27587357 1 23 theme key 137:139 arg1 entrance 67:74 UDP-Glc entrance 59:74 UDP-Glc entrance into the endoplasmic reticulum (ER) of eukaryotic cells 59:130 UDP-Glc entrance into the endoplasmic reticulum (ER) of eukaryotic cells is a key step in the quality control of glycoprotein folding, a mechanism requiring transfer of a Glc residue from the nucleotide sugar (NS) to glycoprotein folding intermediates by the UDP-Glc:glycoprotein glucosyltransferase (UGGT). 27587357 1 23 theme key 137:139 arg1 mechanism 196:204 a mechanism 194:204 a mechanism requiring transfer of a Glc residue from the nucleotide sugar (NS) to glycoprotein folding intermediates by the UDP-Glc:glycoprotein glucosyltransferase (UGGT) 194:364 UDP-Glc entrance into the endoplasmic reticulum (ER) of eukaryotic cells is a key step in the quality control of glycoprotein folding, a mechanism requiring transfer of a Glc residue from the nucleotide sugar (NS) to glycoprotein folding intermediates by the UDP-Glc:glycoprotein glucosyltransferase (UGGT). 27587357 2 24 theme bioinformatics 382:395 arg1 search 397:402 a bioinformatics search 380:402 a bioinformatics search 380:402 According to a bioinformatics search there are only eight genes in the Schizosaccharomyces pombe genome belonging to the three Pfam families to which all known nucleotide-sugar transporters (NSTs) of the secretory pathway belong. 27587357 6 25 theme unconventional 1444:1457 arg1 sequence 1459:1466 an unconventional sequence 1441:1466 an unconventional sequence 1441:1466 We conclude that the hut1+ gene product is involved in UDP-Glc entrance into the ER, but that at least another as yet unknown NST displaying an unconventional sequence operates in the yeast secretory pathway. 27587357 4 26 theme UDP-Glc 983:989 arg1 entrance 994:1001 vivo UDP-Glc ER entrance 978:1001 vivo UDP-Glc ER entrance occurred in Δhut1Δyea4Δgms2 mutants and in cells in which Δhut1 disruption was combined with that of each of four of the genes encoding Golgi-located proteins 978:1160 Here we demonstrate that (1) Δhut1 and Δgpt1 (UGGT null) mutants share several phenotypic features; (2) Δhut1 mutants show a 50% reduction in UDP-Glc transport into ER-derived membranes; (3) in vivo UDP-Glc ER entrance occurred in Δhut1Δyea4Δgms2 mutants and in cells in which Δhut1 disruption was combined with that of each of four of the genes encoding Golgi-located proteins. 27587357 5 27 theme UDP-Glc 1279:1285 arg1 entrance 1290:1297 UDP-Glc ER entrance 1279:1297 UDP-Glc ER entrance 1279:1297 Therefore, disruption of all genes whose products localize to the ER or have an unknown location did not obliterate UDP-Glc ER entrance. 27587357 6 28 theme yeast 1484:1488 arg1 pathway 1500:1506 the yeast secretory pathway 1480:1506 the yeast secretory pathway 1480:1506 We conclude that the hut1+ gene product is involved in UDP-Glc entrance into the ER, but that at least another as yet unknown NST displaying an unconventional sequence operates in the yeast secretory pathway. 27587357 3 29 dep two 621:623 arg1 yea4+ 644:648 yea4+ 644:648 yea4+ 644:648 The protein products of two of them (hut1+ and yea4+) localize to the ER, those of genes gms1+, vrg4+, pet1+, pet2+ and pet3+ to the Golgi, whereas that of gms2+ has an unknown location. 27587357 3 29 dep two 621:623 arg1 hut1+ 634:638 hut1+ 634:638 hut1+ 634:638 The protein products of two of them (hut1+ and yea4+) localize to the ER, those of genes gms1+, vrg4+, pet1+, pet2+ and pet3+ to the Golgi, whereas that of gms2+ has an unknown location. 27587357 5 30 theme genes 1192:1196 arg1 disruption 1174:1183 disruption 1174:1183 disruption of all genes whose products localize to the ER or have an unknown location 1174:1258 Therefore, disruption of all genes whose products localize to the ER or have an unknown location did not obliterate UDP-Glc ER entrance. 27587357 4 31 theme 50 909:910 arg1 % 911:911 % 911:911 % 911:911 Here we demonstrate that (1) Δhut1 and Δgpt1 (UGGT null) mutants share several phenotypic features; (2) Δhut1 mutants show a 50% reduction in UDP-Glc transport into ER-derived membranes; (3) in vivo UDP-Glc ER entrance occurred in Δhut1Δyea4Δgms2 mutants and in cells in which Δhut1 disruption was combined with that of each of four of the genes encoding Golgi-located proteins. 27587357 6 32 theme gene 1327:1330 arg1 product 1332:1338 the hut1+ gene product 1317:1338 the hut1+ gene product 1317:1338 We conclude that the hut1+ gene product is involved in UDP-Glc entrance into the ER, but that at least another as yet unknown NST displaying an unconventional sequence operates in the yeast secretory pathway. 27587357 0 33 theme UDP-Glc 17:23 arg1 entrance 25:32 UDP-Glc entrance 17:32 UDP-Glc entrance 17:32 The conundrum of UDP-Glc entrance into the yeast ER lumen. 27587357 1 34 theme Glc 230:232 arg1 residue 234:240 a Glc residue 228:240 a Glc residue from the nucleotide sugar (NS) 228:271 UDP-Glc entrance into the endoplasmic reticulum (ER) of eukaryotic cells is a key step in the quality control of glycoprotein folding, a mechanism requiring transfer of a Glc residue from the nucleotide sugar (NS) to glycoprotein folding intermediates by the UDP-Glc:glycoprotein glucosyltransferase (UGGT). 27587357 1 35 from transfer 216:223 arg1 NS 269:270 NS 269:270 NS 269:270 UDP-Glc entrance into the endoplasmic reticulum (ER) of eukaryotic cells is a key step in the quality control of glycoprotein folding, a mechanism requiring transfer of a Glc residue from the nucleotide sugar (NS) to glycoprotein folding intermediates by the UDP-Glc:glycoprotein glucosyltransferase (UGGT). 27587357 1 35 from transfer 216:223 arg1 sugar 262:266 the nucleotide sugar 247:266 the nucleotide sugar (NS) 247:271 UDP-Glc entrance into the endoplasmic reticulum (ER) of eukaryotic cells is a key step in the quality control of glycoprotein folding, a mechanism requiring transfer of a Glc residue from the nucleotide sugar (NS) to glycoprotein folding intermediates by the UDP-Glc:glycoprotein glucosyltransferase (UGGT). 27587357 7 36 theme previous 1541:1548 arg1 results 1550:1556 our previous results 1537:1556 our previous results 1537:1556 This conclusion agrees with our previous results showing that UDP-Glc entrance into the yeast ER does not follow the classical NST antiport mechanism. 27587357 4 37 from reduction 913:921 arg1 transport 934:942 UDP-Glc transport 926:942 UDP-Glc transport into ER-derived membranes 926:968 Here we demonstrate that (1) Δhut1 and Δgpt1 (UGGT null) mutants share several phenotypic features; (2) Δhut1 mutants show a 50% reduction in UDP-Glc transport into ER-derived membranes; (3) in vivo UDP-Glc ER entrance occurred in Δhut1Δyea4Δgms2 mutants and in cells in which Δhut1 disruption was combined with that of each of four of the genes encoding Golgi-located proteins. 27587357 4 38 theme several 855:861 arg1 features 874:881 several phenotypic features 855:881 several phenotypic features 855:881 Here we demonstrate that (1) Δhut1 and Δgpt1 (UGGT null) mutants share several phenotypic features; (2) Δhut1 mutants show a 50% reduction in UDP-Glc transport into ER-derived membranes; (3) in vivo UDP-Glc ER entrance occurred in Δhut1Δyea4Δgms2 mutants and in cells in which Δhut1 disruption was combined with that of each of four of the genes encoding Golgi-located proteins. 27587357 1 39 theme residue 234:240 arg1 transfer 216:223 transfer 216:223 transfer of a Glc residue from the nucleotide sugar (NS) to glycoprotein folding intermediates 216:309 UDP-Glc entrance into the endoplasmic reticulum (ER) of eukaryotic cells is a key step in the quality control of glycoprotein folding, a mechanism requiring transfer of a Glc residue from the nucleotide sugar (NS) to glycoprotein folding intermediates by the UDP-Glc:glycoprotein glucosyltransferase (UGGT). 27587357 2 40 dep Schizosaccharomyces 438:456 arg1 pombe 458:462 pombe 458:462 pombe 458:462 According to a bioinformatics search there are only eight genes in the Schizosaccharomyces pombe genome belonging to the three Pfam families to which all known nucleotide-sugar transporters (NSTs) of the secretory pathway belong. 27587357 1 41 theme endoplasmic 85:95 arg1 ER 108:109 ER 108:109 ER 108:109 UDP-Glc entrance into the endoplasmic reticulum (ER) of eukaryotic cells is a key step in the quality control of glycoprotein folding, a mechanism requiring transfer of a Glc residue from the nucleotide sugar (NS) to glycoprotein folding intermediates by the UDP-Glc:glycoprotein glucosyltransferase (UGGT). 27587357 1 41 theme endoplasmic 85:95 arg1 reticulum 97:105 the endoplasmic reticulum 81:105 the endoplasmic reticulum (ER) 81:110 UDP-Glc entrance into the endoplasmic reticulum (ER) of eukaryotic cells is a key step in the quality control of glycoprotein folding, a mechanism requiring transfer of a Glc residue from the nucleotide sugar (NS) to glycoprotein folding intermediates by the UDP-Glc:glycoprotein glucosyltransferase (UGGT). 27587357 1 42 theme quality 153:159 arg1 control 161:167 the quality control 149:167 the quality control of glycoprotein folding 149:191 UDP-Glc entrance into the endoplasmic reticulum (ER) of eukaryotic cells is a key step in the quality control of glycoprotein folding, a mechanism requiring transfer of a Glc residue from the nucleotide sugar (NS) to glycoprotein folding intermediates by the UDP-Glc:glycoprotein glucosyltransferase (UGGT). 27587357 5 43 theme unknown 1243:1249 arg1 location 1251:1258 an unknown location 1240:1258 an unknown location 1240:1258 Therefore, disruption of all genes whose products localize to the ER or have an unknown location did not obliterate UDP-Glc ER entrance. 27587357 7 44 theme classical 1626:1634 arg1 mechanism 1649:1657 the classical NST antiport mechanism 1622:1657 the classical NST antiport mechanism 1622:1657 This conclusion agrees with our previous results showing that UDP-Glc entrance into the yeast ER does not follow the classical NST antiport mechanism. 27587357 4 45 theme Δhut1 1061:1065 arg1 disruption 1067:1076 Δhut1 disruption 1061:1076 Δhut1 disruption 1061:1076 Here we demonstrate that (1) Δhut1 and Δgpt1 (UGGT null) mutants share several phenotypic features; (2) Δhut1 mutants show a 50% reduction in UDP-Glc transport into ER-derived membranes; (3) in vivo UDP-Glc ER entrance occurred in Δhut1Δyea4Δgms2 mutants and in cells in which Δhut1 disruption was combined with that of each of four of the genes encoding Golgi-located proteins. 27587357 4 46 link ER-derived 949:958 arg1 membranes 960:968 ER-derived membranes 949:968 ER-derived membranes 949:968 Here we demonstrate that (1) Δhut1 and Δgpt1 (UGGT null) mutants share several phenotypic features; (2) Δhut1 mutants show a 50% reduction in UDP-Glc transport into ER-derived membranes; (3) in vivo UDP-Glc ER entrance occurred in Δhut1Δyea4Δgms2 mutants and in cells in which Δhut1 disruption was combined with that of each of four of the genes encoding Golgi-located proteins. 27587357 0 47 theme entrance 25:32 arg1 conundrum 4:12 The conundrum 0:12 The conundrum of UDP-Glc entrance into the yeast ER lumen 0:56 The conundrum of UDP-Glc entrance into the yeast ER lumen. 27587357 4 48 dep demonstrate 792:802 arg1 2 885:885 2 885:885 2 885:885 Here we demonstrate that (1) Δhut1 and Δgpt1 (UGGT null) mutants share several phenotypic features; (2) Δhut1 mutants show a 50% reduction in UDP-Glc transport into ER-derived membranes; (3) in vivo UDP-Glc ER entrance occurred in Δhut1Δyea4Δgms2 mutants and in cells in which Δhut1 disruption was combined with that of each of four of the genes encoding Golgi-located proteins. 27587357 4 48 dep demonstrate 792:802 arg1 3 972:972 3 972:972 3 972:972 Here we demonstrate that (1) Δhut1 and Δgpt1 (UGGT null) mutants share several phenotypic features; (2) Δhut1 mutants show a 50% reduction in UDP-Glc transport into ER-derived membranes; (3) in vivo UDP-Glc ER entrance occurred in Δhut1Δyea4Δgms2 mutants and in cells in which Δhut1 disruption was combined with that of each of four of the genes encoding Golgi-located proteins. 27587357 4 48 dep demonstrate 792:802 arg1 show 902:905 show 902:905 show a 50% reduction in UDP-Glc transport into ER-derived membranes 902:968 Here we demonstrate that (1) Δhut1 and Δgpt1 (UGGT null) mutants share several phenotypic features; (2) Δhut1 mutants show a 50% reduction in UDP-Glc transport into ER-derived membranes; (3) in vivo UDP-Glc ER entrance occurred in Δhut1Δyea4Δgms2 mutants and in cells in which Δhut1 disruption was combined with that of each of four of the genes encoding Golgi-located proteins. 27587357 1 49 theme glycoprotein 326:337 arg1 UGGT 360:363 UGGT 360:363 UGGT 360:363 UDP-Glc entrance into the endoplasmic reticulum (ER) of eukaryotic cells is a key step in the quality control of glycoprotein folding, a mechanism requiring transfer of a Glc residue from the nucleotide sugar (NS) to glycoprotein folding intermediates by the UDP-Glc:glycoprotein glucosyltransferase (UGGT). 27587357 1 49 theme glycoprotein 326:337 arg1 glucosyltransferase 339:357 glycoprotein glucosyltransferase 326:357 a mechanism requiring transfer of a Glc residue from the nucleotide sugar (NS) to glycoprotein folding intermediates by the UDP-Glc:glycoprotein glucosyltransferase (UGGT) 194:364 UDP-Glc entrance into the endoplasmic reticulum (ER) of eukaryotic cells is a key step in the quality control of glycoprotein folding, a mechanism requiring transfer of a Glc residue from the nucleotide sugar (NS) to glycoprotein folding intermediates by the UDP-Glc:glycoprotein glucosyltransferase (UGGT). 27587357 4 50 theme phenotypic 863:872 arg1 features 874:881 several phenotypic features 855:881 several phenotypic features 855:881 Here we demonstrate that (1) Δhut1 and Δgpt1 (UGGT null) mutants share several phenotypic features; (2) Δhut1 mutants show a 50% reduction in UDP-Glc transport into ER-derived membranes; (3) in vivo UDP-Glc ER entrance occurred in Δhut1Δyea4Δgms2 mutants and in cells in which Δhut1 disruption was combined with that of each of four of the genes encoding Golgi-located proteins. 27587357 6 51 theme UDP-Glc 1355:1361 arg1 entrance 1363:1370 UDP-Glc entrance 1355:1370 UDP-Glc entrance into the ER 1355:1382 We conclude that the hut1+ gene product is involved in UDP-Glc entrance into the ER, but that at least another as yet unknown NST displaying an unconventional sequence operates in the yeast secretory pathway. 27587357 0 52 theme yeast 43:47 arg1 lumen 52:56 the yeast ER lumen 39:56 the yeast ER lumen 39:56 The conundrum of UDP-Glc entrance into the yeast ER lumen. 27587357 1 53 theme nucleotide 251:260 arg1 NS 269:270 NS 269:270 NS 269:270 UDP-Glc entrance into the endoplasmic reticulum (ER) of eukaryotic cells is a key step in the quality control of glycoprotein folding, a mechanism requiring transfer of a Glc residue from the nucleotide sugar (NS) to glycoprotein folding intermediates by the UDP-Glc:glycoprotein glucosyltransferase (UGGT). 27587357 1 53 theme nucleotide 251:260 arg1 sugar 262:266 the nucleotide sugar 247:266 the nucleotide sugar (NS) 247:271 UDP-Glc entrance into the endoplasmic reticulum (ER) of eukaryotic cells is a key step in the quality control of glycoprotein folding, a mechanism requiring transfer of a Glc residue from the nucleotide sugar (NS) to glycoprotein folding intermediates by the UDP-Glc:glycoprotein glucosyltransferase (UGGT). 27587357 3 54 contain has 759:761 arg1 that 745:748 that 745:748 that 745:748 The protein products of two of them (hut1+ and yea4+) localize to the ER, those of genes gms1+, vrg4+, pet1+, pet2+ and pet3+ to the Golgi, whereas that of gms2+ has an unknown location. 27587357 3 54 contain has 759:761 arg2 location 774:781 an unknown location 763:781 an unknown location 763:781 The protein products of two of them (hut1+ and yea4+) localize to the ER, those of genes gms1+, vrg4+, pet1+, pet2+ and pet3+ to the Golgi, whereas that of gms2+ has an unknown location. 27587357 6 55 theme unknown 1418:1424 arg1 NST 1426:1428 another as yet unknown NST 1403:1428 at least another as yet unknown NST displaying an unconventional sequence 1394:1466 We conclude that the hut1+ gene product is involved in UDP-Glc entrance into the ER, but that at least another as yet unknown NST displaying an unconventional sequence operates in the yeast secretory pathway. 27587357 5 56 theme ER 1287:1288 arg1 entrance 1290:1297 UDP-Glc ER entrance 1279:1297 UDP-Glc ER entrance 1279:1297 Therefore, disruption of all genes whose products localize to the ER or have an unknown location did not obliterate UDP-Glc ER entrance. 27587357 7 57 theme NST 1636:1638 arg1 mechanism 1649:1657 the classical NST antiport mechanism 1622:1657 the classical NST antiport mechanism 1622:1657 This conclusion agrees with our previous results showing that UDP-Glc entrance into the yeast ER does not follow the classical NST antiport mechanism. 27587357 2 58 theme Pfam 494:497 arg1 families 499:506 the three Pfam families 484:506 the three Pfam families to which all known nucleotide-sugar transporters (NSTs) of the secretory pathway belong 484:594 According to a bioinformatics search there are only eight genes in the Schizosaccharomyces pombe genome belonging to the three Pfam families to which all known nucleotide-sugar transporters (NSTs) of the secretory pathway belong. 27587357 4 59 theme vivo 978:981 arg1 entrance 994:1001 vivo UDP-Glc ER entrance 978:1001 vivo UDP-Glc ER entrance occurred in Δhut1Δyea4Δgms2 mutants and in cells in which Δhut1 disruption was combined with that of each of four of the genes encoding Golgi-located proteins 978:1160 Here we demonstrate that (1) Δhut1 and Δgpt1 (UGGT null) mutants share several phenotypic features; (2) Δhut1 mutants show a 50% reduction in UDP-Glc transport into ER-derived membranes; (3) in vivo UDP-Glc ER entrance occurred in Δhut1Δyea4Δgms2 mutants and in cells in which Δhut1 disruption was combined with that of each of four of the genes encoding Golgi-located proteins. 27587357 4 60 theme Δhut1 888:892 arg1 mutants 894:900 Δhut1 mutants 888:900 Δhut1 mutants 888:900 Here we demonstrate that (1) Δhut1 and Δgpt1 (UGGT null) mutants share several phenotypic features; (2) Δhut1 mutants show a 50% reduction in UDP-Glc transport into ER-derived membranes; (3) in vivo UDP-Glc ER entrance occurred in Δhut1Δyea4Δgms2 mutants and in cells in which Δhut1 disruption was combined with that of each of four of the genes encoding Golgi-located proteins. 27587357 4 61 theme Golgi-located 1139:1151 arg1 proteins 1153:1160 Golgi-located proteins 1139:1160 Golgi-located proteins 1139:1160 Here we demonstrate that (1) Δhut1 and Δgpt1 (UGGT null) mutants share several phenotypic features; (2) Δhut1 mutants show a 50% reduction in UDP-Glc transport into ER-derived membranes; (3) in vivo UDP-Glc ER entrance occurred in Δhut1Δyea4Δgms2 mutants and in cells in which Δhut1 disruption was combined with that of each of four of the genes encoding Golgi-located proteins. 27587357 4 62 dep Δhut1 813:817 arg1 1 810:810 1 810:810 1 810:810 Here we demonstrate that (1) Δhut1 and Δgpt1 (UGGT null) mutants share several phenotypic features; (2) Δhut1 mutants show a 50% reduction in UDP-Glc transport into ER-derived membranes; (3) in vivo UDP-Glc ER entrance occurred in Δhut1Δyea4Δgms2 mutants and in cells in which Δhut1 disruption was combined with that of each of four of the genes encoding Golgi-located proteins. 27587357 4 62 dep Δhut1 813:817 arg1 mutants 841:847 mutants 841:847 mutants 841:847 Here we demonstrate that (1) Δhut1 and Δgpt1 (UGGT null) mutants share several phenotypic features; (2) Δhut1 mutants show a 50% reduction in UDP-Glc transport into ER-derived membranes; (3) in vivo UDP-Glc ER entrance occurred in Δhut1Δyea4Δgms2 mutants and in cells in which Δhut1 disruption was combined with that of each of four of the genes encoding Golgi-located proteins. 27587357 1 63 theme glycoprotein 172:183 arg1 folding 185:191 glycoprotein folding 172:191 glycoprotein folding 172:191 UDP-Glc entrance into the endoplasmic reticulum (ER) of eukaryotic cells is a key step in the quality control of glycoprotein folding, a mechanism requiring transfer of a Glc residue from the nucleotide sugar (NS) to glycoprotein folding intermediates by the UDP-Glc:glycoprotein glucosyltransferase (UGGT). 27587357 1 64 dep mechanism 196:204 arg1 UGGT 360:363 UGGT 360:363 UGGT 360:363 UDP-Glc entrance into the endoplasmic reticulum (ER) of eukaryotic cells is a key step in the quality control of glycoprotein folding, a mechanism requiring transfer of a Glc residue from the nucleotide sugar (NS) to glycoprotein folding intermediates by the UDP-Glc:glycoprotein glucosyltransferase (UGGT). 27587357 1 64 dep mechanism 196:204 arg1 glucosyltransferase 339:357 glycoprotein glucosyltransferase 326:357 a mechanism requiring transfer of a Glc residue from the nucleotide sugar (NS) to glycoprotein folding intermediates by the UDP-Glc:glycoprotein glucosyltransferase (UGGT) 194:364 UDP-Glc entrance into the endoplasmic reticulum (ER) of eukaryotic cells is a key step in the quality control of glycoprotein folding, a mechanism requiring transfer of a Glc residue from the nucleotide sugar (NS) to glycoprotein folding intermediates by the UDP-Glc:glycoprotein glucosyltransferase (UGGT). 27587357 7 65 theme yeast 1597:1601 arg1 ER 1603:1604 the yeast ER 1593:1604 the yeast ER 1593:1604 This conclusion agrees with our previous results showing that UDP-Glc entrance into the yeast ER does not follow the classical NST antiport mechanism. 27587357 1 66 from step 141:144 arg1 control 161:167 the quality control 149:167 the quality control of glycoprotein folding 149:191 UDP-Glc entrance into the endoplasmic reticulum (ER) of eukaryotic cells is a key step in the quality control of glycoprotein folding, a mechanism requiring transfer of a Glc residue from the nucleotide sugar (NS) to glycoprotein folding intermediates by the UDP-Glc:glycoprotein glucosyltransferase (UGGT). 27587357 7 67 theme antiport 1640:1647 arg1 mechanism 1649:1657 the classical NST antiport mechanism 1622:1657 the classical NST antiport mechanism 1622:1657 This conclusion agrees with our previous results showing that UDP-Glc entrance into the yeast ER does not follow the classical NST antiport mechanism. 27587357 3 68 theme pet3+ 717:721 arg1 genes 680:684 genes 680:684 genes gms1+, vrg4+, pet1+, pet2+ and pet3+ to the Golgi 680:734 The protein products of two of them (hut1+ and yea4+) localize to the ER, those of genes gms1+, vrg4+, pet1+, pet2+ and pet3+ to the Golgi, whereas that of gms2+ has an unknown location. 27587357 1 69 theme folding 185:191 arg1 control 161:167 the quality control 149:167 the quality control of glycoprotein folding 149:191 UDP-Glc entrance into the endoplasmic reticulum (ER) of eukaryotic cells is a key step in the quality control of glycoprotein folding, a mechanism requiring transfer of a Glc residue from the nucleotide sugar (NS) to glycoprotein folding intermediates by the UDP-Glc:glycoprotein glucosyltransferase (UGGT). 27587357 4 70 theme % 911:911 arg1 reduction 913:921 a 50% reduction 907:921 a 50% reduction in UDP-Glc transport into ER-derived membranes 907:968 Here we demonstrate that (1) Δhut1 and Δgpt1 (UGGT null) mutants share several phenotypic features; (2) Δhut1 mutants show a 50% reduction in UDP-Glc transport into ER-derived membranes; (3) in vivo UDP-Glc ER entrance occurred in Δhut1Δyea4Δgms2 mutants and in cells in which Δhut1 disruption was combined with that of each of four of the genes encoding Golgi-located proteins. 27587357 3 71 theme protein 601:607 arg1 products 609:616 The protein products 597:616 The protein products of two of them (hut1+ and yea4+) 597:649 The protein products of two of them (hut1+ and yea4+) localize to the ER, those of genes gms1+, vrg4+, pet1+, pet2+ and pet3+ to the Golgi, whereas that of gms2+ has an unknown location. 27587357 4 72 theme ER-derived 949:958 arg1 membranes 960:968 ER-derived membranes 949:968 ER-derived membranes 949:968 Here we demonstrate that (1) Δhut1 and Δgpt1 (UGGT null) mutants share several phenotypic features; (2) Δhut1 mutants show a 50% reduction in UDP-Glc transport into ER-derived membranes; (3) in vivo UDP-Glc ER entrance occurred in Δhut1Δyea4Δgms2 mutants and in cells in which Δhut1 disruption was combined with that of each of four of the genes encoding Golgi-located proteins. 27587357 1 73 gly glycoprotein 326:337 arg1 glycoprotein 326:337 glycoprotein glucosyltransferase 326:357 a mechanism requiring transfer of a Glc residue from the nucleotide sugar (NS) to glycoprotein folding intermediates by the UDP-Glc:glycoprotein glucosyltransferase (UGGT) 194:364 UDP-Glc entrance into the endoplasmic reticulum (ER) of eukaryotic cells is a key step in the quality control of glycoprotein folding, a mechanism requiring transfer of a Glc residue from the nucleotide sugar (NS) to glycoprotein folding intermediates by the UDP-Glc:glycoprotein glucosyltransferase (UGGT). 27587357 3 74 theme gms1+ 686:690 arg1 genes 680:684 genes 680:684 genes gms1+, vrg4+, pet1+, pet2+ and pet3+ to the Golgi 680:734 The protein products of two of them (hut1+ and yea4+) localize to the ER, those of genes gms1+, vrg4+, pet1+, pet2+ and pet3+ to the Golgi, whereas that of gms2+ has an unknown location. 27587357 0 75 theme ER 49:50 arg1 lumen 52:56 the yeast ER lumen 39:56 the yeast ER lumen 39:56 The conundrum of UDP-Glc entrance into the yeast ER lumen. 27587357 3 76 theme them 628:631 arg1 them 628:631 them 628:631 them 628:631 The protein products of two of them (hut1+ and yea4+) localize to the ER, those of genes gms1+, vrg4+, pet1+, pet2+ and pet3+ to the Golgi, whereas that of gms2+ has an unknown location. 27587357 3 76 theme them 628:631 arg1 two 621:623 two 621:623 two 621:623 The protein products of two of them (hut1+ and yea4+) localize to the ER, those of genes gms1+, vrg4+, pet1+, pet2+ and pet3+ to the Golgi, whereas that of gms2+ has an unknown location. 27587357 6 77 theme hut1+ 1321:1325 arg1 product 1332:1338 the hut1+ gene product 1317:1338 the hut1+ gene product 1317:1338 We conclude that the hut1+ gene product is involved in UDP-Glc entrance into the ER, but that at least another as yet unknown NST displaying an unconventional sequence operates in the yeast secretory pathway. 27587357 1 78 theme eukaryotic 115:124 arg1 cells 126:130 eukaryotic cells 115:130 eukaryotic cells 115:130 UDP-Glc entrance into the endoplasmic reticulum (ER) of eukaryotic cells is a key step in the quality control of glycoprotein folding, a mechanism requiring transfer of a Glc residue from the nucleotide sugar (NS) to glycoprotein folding intermediates by the UDP-Glc:glycoprotein glucosyltransferase (UGGT). 27587357 4 79 theme genes 1124:1128 arg1 four 1112:1115 four 1112:1115 four 1112:1115 Here we demonstrate that (1) Δhut1 and Δgpt1 (UGGT null) mutants share several phenotypic features; (2) Δhut1 mutants show a 50% reduction in UDP-Glc transport into ER-derived membranes; (3) in vivo UDP-Glc ER entrance occurred in Δhut1Δyea4Δgms2 mutants and in cells in which Δhut1 disruption was combined with that of each of four of the genes encoding Golgi-located proteins. 27587357 4 79 theme genes 1124:1128 arg1 genes 1124:1128 the genes 1120:1128 the genes encoding Golgi-located proteins 1120:1160 Here we demonstrate that (1) Δhut1 and Δgpt1 (UGGT null) mutants share several phenotypic features; (2) Δhut1 mutants show a 50% reduction in UDP-Glc transport into ER-derived membranes; (3) in vivo UDP-Glc ER entrance occurred in Δhut1Δyea4Δgms2 mutants and in cells in which Δhut1 disruption was combined with that of each of four of the genes encoding Golgi-located proteins. 27807044 1 0 theme invariant 299:307 arg1 chain 309:313 invariant chain 299:313 invariant chain (Ii)-FKBP in the ER 299:333 Golgi-specific sialyltransferase (ST) expressed as a chimera with the rapamycin-binding domain of mTOR, FRB, relocates to the endoplasmic reticulum (ER) in cells exposed to rapamycin that also express invariant chain (Ii)-FKBP in the ER. 27807044 1 0 theme invariant 299:307 arg1 Ii 316:317 Ii 316:317 Ii 316:317 Golgi-specific sialyltransferase (ST) expressed as a chimera with the rapamycin-binding domain of mTOR, FRB, relocates to the endoplasmic reticulum (ER) in cells exposed to rapamycin that also express invariant chain (Ii)-FKBP in the ER. 27807044 7 1 theme Golgi-specific 909:922 arg1 glycosylation 933:945 Golgi-specific O-linked glycosylation 909:945 Golgi-specific O-linked glycosylation of a resident ER protein 909:970 In addition, Golgi-specific O-linked glycosylation of a resident ER protein occurs only upon artificial fusion of Golgi membranes with ER. 27807044 1 2 theme endoplasmic 224:234 arg1 reticulum 236:244 the endoplasmic reticulum 220:244 the endoplasmic reticulum (ER) 220:249 Golgi-specific sialyltransferase (ST) expressed as a chimera with the rapamycin-binding domain of mTOR, FRB, relocates to the endoplasmic reticulum (ER) in cells exposed to rapamycin that also express invariant chain (Ii)-FKBP in the ER. 27807044 1 2 theme endoplasmic 224:234 arg1 ER 247:248 ER 247:248 ER 247:248 Golgi-specific sialyltransferase (ST) expressed as a chimera with the rapamycin-binding domain of mTOR, FRB, relocates to the endoplasmic reticulum (ER) in cells exposed to rapamycin that also express invariant chain (Ii)-FKBP in the ER. 27807044 0 3 theme protein 68:74 arg1 secretion 76:84 protein secretion 68:84 protein secretion 68:84 Golgi enzymes do not cycle through the endoplasmic reticulum during protein secretion or mitosis. 27807044 1 4 with chimera 151:157 arg1 mTOR 196:199 mTOR 196:199 mTOR 196:199 Golgi-specific sialyltransferase (ST) expressed as a chimera with the rapamycin-binding domain of mTOR, FRB, relocates to the endoplasmic reticulum (ER) in cells exposed to rapamycin that also express invariant chain (Ii)-FKBP in the ER. 27807044 1 4 with chimera 151:157 arg1 domain 186:191 the rapamycin-binding domain 164:191 the rapamycin-binding domain of mTOR 164:199 Golgi-specific sialyltransferase (ST) expressed as a chimera with the rapamycin-binding domain of mTOR, FRB, relocates to the endoplasmic reticulum (ER) in cells exposed to rapamycin that also express invariant chain (Ii)-FKBP in the ER. 27807044 1 4 with chimera 151:157 arg1 FRB 202:204 FRB 202:204 FRB 202:204 Golgi-specific sialyltransferase (ST) expressed as a chimera with the rapamycin-binding domain of mTOR, FRB, relocates to the endoplasmic reticulum (ER) in cells exposed to rapamycin that also express invariant chain (Ii)-FKBP in the ER. 27807044 6 5 theme ST-FRB 822:827 arg1 cycles 829:834 ST-FRB cycles 822:834 ST-FRB cycles 822:834 Thus ST-FRB cycles artificially by binding to FKBP domain-containing proteins. 27807044 4 6 from ST-FRB 615:620 arg1 Golgi 629:633 the Golgi 625:633 the Golgi 625:633 This is because ER-Golgi-cycling FKBP proteins contain a C-terminal KDEL-like sequence, bind ST-FRB in the Golgi, and are transported together back to the ER by KDEL receptor-mediated retrograde transport. 27807044 8 7 theme appreciable 1103:1113 arg1 mixing 1115:1120 no appreciable mixing 1100:1120 no appreciable mixing of Golgi-resident enzymes with ER 1100:1154 Together these findings support the consensus view that there is no appreciable mixing of Golgi-resident enzymes with ER under normal conditions. 27807044 7 8 with fusion 1000:1005 arg1 ER 1031:1032 ER 1031:1032 ER 1031:1032 In addition, Golgi-specific O-linked glycosylation of a resident ER protein occurs only upon artificial fusion of Golgi membranes with ER. 27807044 1 9 dep sialyltransferase 113:129 arg1 ST 132:133 ST 132:133 ST 132:133 Golgi-specific sialyltransferase (ST) expressed as a chimera with the rapamycin-binding domain of mTOR, FRB, relocates to the endoplasmic reticulum (ER) in cells exposed to rapamycin that also express invariant chain (Ii)-FKBP in the ER. 27807044 5 10 theme ST-FRB 786:791 arg1 trapping 774:781 trapping 774:781 trapping of ST-FRB 774:791 Moreover, depletion of KDEL receptor prevents trapping of ST-FRB in the ER by rapamycin. 27807044 1 11 from ER 332:333 arg1 -FKBP 319:323 -FKBP 319:323 -FKBP 319:323 Golgi-specific sialyltransferase (ST) expressed as a chimera with the rapamycin-binding domain of mTOR, FRB, relocates to the endoplasmic reticulum (ER) in cells exposed to rapamycin that also express invariant chain (Ii)-FKBP in the ER. 27807044 1 12 theme -FKBP 319:323 arg1 chain 309:313 invariant chain 299:313 invariant chain (Ii)-FKBP in the ER 299:333 Golgi-specific sialyltransferase (ST) expressed as a chimera with the rapamycin-binding domain of mTOR, FRB, relocates to the endoplasmic reticulum (ER) in cells exposed to rapamycin that also express invariant chain (Ii)-FKBP in the ER. 27807044 1 12 theme -FKBP 319:323 arg1 Ii 316:317 Ii 316:317 Ii 316:317 Golgi-specific sialyltransferase (ST) expressed as a chimera with the rapamycin-binding domain of mTOR, FRB, relocates to the endoplasmic reticulum (ER) in cells exposed to rapamycin that also express invariant chain (Ii)-FKBP in the ER. 27807044 8 13 dep view 1081:1084 arg1 is 1097:1098 is 1097:1098 is no appreciable mixing of Golgi-resident enzymes with ER under normal conditions 1097:1178 Together these findings support the consensus view that there is no appreciable mixing of Golgi-resident enzymes with ER under normal conditions. 27807044 7 14 theme Golgi 1010:1014 arg1 membranes 1016:1024 Golgi membranes 1010:1024 Golgi membranes 1010:1024 In addition, Golgi-specific O-linked glycosylation of a resident ER protein occurs only upon artificial fusion of Golgi membranes with ER. 27807044 4 15 theme KDEL 683:686 arg1 transport 717:725 KDEL receptor-mediated retrograde transport 683:725 KDEL receptor-mediated retrograde transport 683:725 This is because ER-Golgi-cycling FKBP proteins contain a C-terminal KDEL-like sequence, bind ST-FRB in the Golgi, and are transported together back to the ER by KDEL receptor-mediated retrograde transport. 27807044 4 16 theme KDEL-like 590:598 arg1 sequence 600:607 a C-terminal KDEL-like sequence 577:607 a C-terminal KDEL-like sequence 577:607 This is because ER-Golgi-cycling FKBP proteins contain a C-terminal KDEL-like sequence, bind ST-FRB in the Golgi, and are transported together back to the ER by KDEL receptor-mediated retrograde transport. 27807044 1 17 from -FKBP 319:323 arg1 ER 332:333 the ER 328:333 the ER 328:333 Golgi-specific sialyltransferase (ST) expressed as a chimera with the rapamycin-binding domain of mTOR, FRB, relocates to the endoplasmic reticulum (ER) in cells exposed to rapamycin that also express invariant chain (Ii)-FKBP in the ER. 27807044 7 18 theme membranes 1016:1024 arg1 fusion 1000:1005 artificial fusion 989:1005 artificial fusion of Golgi membranes with ER 989:1032 In addition, Golgi-specific O-linked glycosylation of a resident ER protein occurs only upon artificial fusion of Golgi membranes with ER. 27807044 1 19 theme rapamycin-binding 168:184 arg1 mTOR 196:199 mTOR 196:199 mTOR 196:199 Golgi-specific sialyltransferase (ST) expressed as a chimera with the rapamycin-binding domain of mTOR, FRB, relocates to the endoplasmic reticulum (ER) in cells exposed to rapamycin that also express invariant chain (Ii)-FKBP in the ER. 27807044 1 19 theme rapamycin-binding 168:184 arg1 domain 186:191 the rapamycin-binding domain 164:191 the rapamycin-binding domain of mTOR 164:199 Golgi-specific sialyltransferase (ST) expressed as a chimera with the rapamycin-binding domain of mTOR, FRB, relocates to the endoplasmic reticulum (ER) in cells exposed to rapamycin that also express invariant chain (Ii)-FKBP in the ER. 27807044 1 19 theme rapamycin-binding 168:184 arg1 FRB 202:204 FRB 202:204 FRB 202:204 Golgi-specific sialyltransferase (ST) expressed as a chimera with the rapamycin-binding domain of mTOR, FRB, relocates to the endoplasmic reticulum (ER) in cells exposed to rapamycin that also express invariant chain (Ii)-FKBP in the ER. 27807044 0 20 theme Golgi 0:4 arg1 enzymes 6:12 Golgi enzymes 0:12 Golgi enzymes 0:12 Golgi enzymes do not cycle through the endoplasmic reticulum during protein secretion or mitosis. 27807044 7 21 gly glycosylation 933:945 arg2 addition 899:906 addition 899:906 addition 899:906 In addition, Golgi-specific O-linked glycosylation of a resident ER protein occurs only upon artificial fusion of Golgi membranes with ER. 27807044 7 21 gly glycosylation 933:945 arg1 protein 964:970 a resident ER protein 950:970 a resident ER protein 950:970 In addition, Golgi-specific O-linked glycosylation of a resident ER protein occurs only upon artificial fusion of Golgi membranes with ER. 27807044 8 22 theme enzymes 1140:1146 arg1 mixing 1115:1120 no appreciable mixing 1100:1120 no appreciable mixing of Golgi-resident enzymes with ER 1100:1154 Together these findings support the consensus view that there is no appreciable mixing of Golgi-resident enzymes with ER under normal conditions. 27807044 5 23 theme receptor 756:763 arg1 depletion 738:746 depletion 738:746 depletion of KDEL receptor 738:763 Moreover, depletion of KDEL receptor prevents trapping of ST-FRB in the ER by rapamycin. 27807044 5 24 theme KDEL 751:754 arg1 receptor 756:763 KDEL receptor 751:763 KDEL receptor 751:763 Moreover, depletion of KDEL receptor prevents trapping of ST-FRB in the ER by rapamycin. 27807044 7 25 link O-linked 924:931 arg1 glycosylation 933:945 Golgi-specific O-linked glycosylation 909:945 Golgi-specific O-linked glycosylation of a resident ER protein 909:970 In addition, Golgi-specific O-linked glycosylation of a resident ER protein occurs only upon artificial fusion of Golgi membranes with ER. 27807044 4 26 theme receptor-mediated 688:704 arg1 transport 717:725 KDEL receptor-mediated retrograde transport 683:725 KDEL receptor-mediated retrograde transport 683:725 This is because ER-Golgi-cycling FKBP proteins contain a C-terminal KDEL-like sequence, bind ST-FRB in the Golgi, and are transported together back to the ER by KDEL receptor-mediated retrograde transport. 27807044 1 27 theme Golgi-specific 98:111 arg1 sialyltransferase 113:129 Golgi-specific sialyltransferase 98:129 Golgi-specific sialyltransferase (ST) expressed as a chimera with the rapamycin-binding domain of mTOR, FRB, 98:205 Golgi-specific sialyltransferase (ST) expressed as a chimera with the rapamycin-binding domain of mTOR, FRB, relocates to the endoplasmic reticulum (ER) in cells exposed to rapamycin that also express invariant chain (Ii)-FKBP in the ER. 27807044 1 28 theme mTOR 196:199 arg1 mTOR 196:199 mTOR 196:199 mTOR 196:199 Golgi-specific sialyltransferase (ST) expressed as a chimera with the rapamycin-binding domain of mTOR, FRB, relocates to the endoplasmic reticulum (ER) in cells exposed to rapamycin that also express invariant chain (Ii)-FKBP in the ER. 27807044 1 28 theme mTOR 196:199 arg1 domain 186:191 the rapamycin-binding domain 164:191 the rapamycin-binding domain of mTOR 164:199 Golgi-specific sialyltransferase (ST) expressed as a chimera with the rapamycin-binding domain of mTOR, FRB, relocates to the endoplasmic reticulum (ER) in cells exposed to rapamycin that also express invariant chain (Ii)-FKBP in the ER. 27807044 1 28 theme mTOR 196:199 arg1 FRB 202:204 FRB 202:204 FRB 202:204 Golgi-specific sialyltransferase (ST) expressed as a chimera with the rapamycin-binding domain of mTOR, FRB, relocates to the endoplasmic reticulum (ER) in cells exposed to rapamycin that also express invariant chain (Ii)-FKBP in the ER. 27807044 7 29 theme artificial 989:998 arg1 fusion 1000:1005 artificial fusion 989:1005 artificial fusion of Golgi membranes with ER 989:1032 In addition, Golgi-specific O-linked glycosylation of a resident ER protein occurs only upon artificial fusion of Golgi membranes with ER. 27807044 4 30 theme C-terminal 579:588 arg1 sequence 600:607 a C-terminal KDEL-like sequence 577:607 a C-terminal KDEL-like sequence 577:607 This is because ER-Golgi-cycling FKBP proteins contain a C-terminal KDEL-like sequence, bind ST-FRB in the Golgi, and are transported together back to the ER by KDEL receptor-mediated retrograde transport. 27807044 6 31 theme domain-containing 868:884 arg1 proteins 886:893 FKBP domain-containing proteins 863:893 FKBP domain-containing proteins 863:893 Thus ST-FRB cycles artificially by binding to FKBP domain-containing proteins. 27807044 7 32 theme resident 952:959 arg1 protein 964:970 a resident ER protein 950:970 a resident ER protein 950:970 In addition, Golgi-specific O-linked glycosylation of a resident ER protein occurs only upon artificial fusion of Golgi membranes with ER. 27807044 0 33 theme endoplasmic 39:49 arg1 reticulum 51:59 the endoplasmic reticulum 35:59 the endoplasmic reticulum during protein secretion or mitosis 35:95 Golgi enzymes do not cycle through the endoplasmic reticulum during protein secretion or mitosis. 27807044 6 34 theme FKBP 863:866 arg1 proteins 886:893 FKBP domain-containing proteins 863:893 FKBP domain-containing proteins 863:893 Thus ST-FRB cycles artificially by binding to FKBP domain-containing proteins. 27807044 4 35 contain contain 569:575 arg1 proteins 560:567 ER-Golgi-cycling FKBP proteins 538:567 ER-Golgi-cycling FKBP proteins 538:567 This is because ER-Golgi-cycling FKBP proteins contain a C-terminal KDEL-like sequence, bind ST-FRB in the Golgi, and are transported together back to the ER by KDEL receptor-mediated retrograde transport. 27807044 4 35 contain contain 569:575 arg2 sequence 600:607 a C-terminal KDEL-like sequence 577:607 a C-terminal KDEL-like sequence 577:607 This is because ER-Golgi-cycling FKBP proteins contain a C-terminal KDEL-like sequence, bind ST-FRB in the Golgi, and are transported together back to the ER by KDEL receptor-mediated retrograde transport. 27807044 3 36 theme rapamycin 502:510 arg1 addition 512:519 rapamycin addition 502:519 rapamycin addition 502:519 We show that ST-FRB is trapped in the ER even without Ii-FKBP upon rapamycin addition. 27807044 7 37 theme ER 961:962 arg1 protein 964:970 a resident ER protein 950:970 a resident ER protein 950:970 In addition, Golgi-specific O-linked glycosylation of a resident ER protein occurs only upon artificial fusion of Golgi membranes with ER. 27807044 7 38 theme protein 964:970 arg1 glycosylation 933:945 Golgi-specific O-linked glycosylation 909:945 Golgi-specific O-linked glycosylation of a resident ER protein 909:970 In addition, Golgi-specific O-linked glycosylation of a resident ER protein occurs only upon artificial fusion of Golgi membranes with ER. 27807044 8 39 with mixing 1115:1120 arg1 ER 1153:1154 ER 1153:1154 ER 1153:1154 Together these findings support the consensus view that there is no appreciable mixing of Golgi-resident enzymes with ER under normal conditions. 27807044 4 40 theme retrograde 706:715 arg1 transport 717:725 KDEL receptor-mediated retrograde transport 683:725 KDEL receptor-mediated retrograde transport 683:725 This is because ER-Golgi-cycling FKBP proteins contain a C-terminal KDEL-like sequence, bind ST-FRB in the Golgi, and are transported together back to the ER by KDEL receptor-mediated retrograde transport. 27807044 7 41 theme O-linked 924:931 arg1 glycosylation 933:945 Golgi-specific O-linked glycosylation 909:945 Golgi-specific O-linked glycosylation of a resident ER protein 909:970 In addition, Golgi-specific O-linked glycosylation of a resident ER protein occurs only upon artificial fusion of Golgi membranes with ER. 27807044 8 42 theme consensus 1071:1079 arg1 view 1081:1084 the consensus view 1067:1084 the consensus view that there is no appreciable mixing of Golgi-resident enzymes with ER under normal conditions 1067:1178 Together these findings support the consensus view that there is no appreciable mixing of Golgi-resident enzymes with ER under normal conditions. 27807044 4 43 theme FKBP 555:558 arg1 proteins 560:567 ER-Golgi-cycling FKBP proteins 538:567 ER-Golgi-cycling FKBP proteins 538:567 This is because ER-Golgi-cycling FKBP proteins contain a C-terminal KDEL-like sequence, bind ST-FRB in the Golgi, and are transported together back to the ER by KDEL receptor-mediated retrograde transport. 27807044 8 44 theme normal 1162:1167 arg1 conditions 1169:1178 normal conditions 1162:1178 normal conditions 1162:1178 Together these findings support the consensus view that there is no appreciable mixing of Golgi-resident enzymes with ER under normal conditions. 27807044 8 45 theme Golgi-resident 1125:1138 arg1 enzymes 1140:1146 Golgi-resident enzymes 1125:1146 Golgi-resident enzymes 1125:1146 Together these findings support the consensus view that there is no appreciable mixing of Golgi-resident enzymes with ER under normal conditions. 27807044 2 46 theme Golgi-resident 380:393 arg1 enzymes 395:401 Golgi-resident enzymes 380:401 Golgi-resident enzymes 380:401 This result has been taken to indicate that Golgi-resident enzymes cycle to the ER constitutively. 27807044 4 47 theme ER-Golgi-cycling 538:553 arg1 proteins 560:567 ER-Golgi-cycling FKBP proteins 538:567 ER-Golgi-cycling FKBP proteins 538:567 This is because ER-Golgi-cycling FKBP proteins contain a C-terminal KDEL-like sequence, bind ST-FRB in the Golgi, and are transported together back to the ER by KDEL receptor-mediated retrograde transport. 25468754 6 0 from substrate 962:970 arg1 Drosophila 975:984 Drosophila 975:984 Drosophila 975:984 We demonstrate that Ph mutants lacking the S/T stretch reproduce the phenotype of ogt mutants, suggesting that the S/T stretch in Ph is the key Ogt substrate in Drosophila. 25468754 6 1 theme key 954:956 arg1 substrate 962:970 the key Ogt substrate 950:970 the key Ogt substrate in Drosophila 950:984 We demonstrate that Ph mutants lacking the S/T stretch reproduce the phenotype of ogt mutants, suggesting that the S/T stretch in Ph is the key Ogt substrate in Drosophila. 25468754 6 1 theme key 954:956 arg1 stretch 933:939 the S/T stretch 925:939 the S/T stretch in Ph 925:945 We demonstrate that Ph mutants lacking the S/T stretch reproduce the phenotype of ogt mutants, suggesting that the S/T stretch in Ph is the key Ogt substrate in Drosophila. 25468754 1 2 theme cytosolic 180:188 arg1 proteins 190:197 nuclear and cytosolic proteins 168:197 nuclear and cytosolic proteins 168:197 The glycosyltransferase Ogt adds O-linked N-Acetylglucosamine (O-GlcNAc) moieties to nuclear and cytosolic proteins. 25468754 5 3 theme Full 710:713 arg1 activity 728:735 Full Ph repressor activity 710:735 Full Ph repressor activity in vivo 710:743 Full Ph repressor activity in vivo requires both the SAM domain and O-GlcNAcylation of the S/T stretch. 25468754 4 4 from O-GlcNAcylation 506:520 arg1 Ph 561:562 Ph 561:562 Ph 561:562 O-GlcNAcylation of a serine/threonine (S/T) stretch in Ph is critical to prevent nonproductive aggregation of both Drosophila and human Ph via their C-terminal sterile alpha motif (SAM) domains in vitro. 25468754 4 5 theme nonproductive 587:599 arg1 aggregation 601:611 nonproductive aggregation 587:611 nonproductive aggregation of both Drosophila and human Ph 587:643 O-GlcNAcylation of a serine/threonine (S/T) stretch in Ph is critical to prevent nonproductive aggregation of both Drosophila and human Ph via their C-terminal sterile alpha motif (SAM) domains in vitro. 25468754 5 6 theme Ph 715:716 arg1 activity 728:735 Full Ph repressor activity 710:735 Full Ph repressor activity in vivo 710:743 Full Ph repressor activity in vivo requires both the SAM domain and O-GlcNAcylation of the S/T stretch. 25468754 3 7 theme protein 377:383 arg1 Polyhomeotic 385:396 The Polycomb protein Polyhomeotic 364:396 The Polycomb protein Polyhomeotic (Ph) 364:401 The Polycomb protein Polyhomeotic (Ph), an Ogt substrate, forms large aggregates in the absence of O-GlcNAcylation both in vivo and in vitro. 25468754 3 7 theme protein 377:383 arg1 substrate 411:419 an Ogt substrate 404:419 an Ogt substrate 404:419 The Polycomb protein Polyhomeotic (Ph), an Ogt substrate, forms large aggregates in the absence of O-GlcNAcylation both in vivo and in vitro. 25468754 3 7 theme protein 377:383 arg1 Ph 399:400 Ph 399:400 Ph 399:400 The Polycomb protein Polyhomeotic (Ph), an Ogt substrate, forms large aggregates in the absence of O-GlcNAcylation both in vivo and in vitro. 25468754 4 8 theme C-terminal 655:664 arg1 SAM 687:689 SAM 687:689 SAM 687:689 O-GlcNAcylation of a serine/threonine (S/T) stretch in Ph is critical to prevent nonproductive aggregation of both Drosophila and human Ph via their C-terminal sterile alpha motif (SAM) domains in vitro. 25468754 4 8 theme C-terminal 655:664 arg1 motif 680:684 C-terminal sterile alpha motif 655:684 their C-terminal sterile alpha motif (SAM) domains 649:698 O-GlcNAcylation of a serine/threonine (S/T) stretch in Ph is critical to prevent nonproductive aggregation of both Drosophila and human Ph via their C-terminal sterile alpha motif (SAM) domains in vitro. 25468754 7 9 theme SAM 1083:1085 arg1 domain 1087:1092 its SAM domain 1079:1092 its SAM domain 1079:1092 We propose that O-GlcNAcylation is needed for Ph to form functional, ordered assemblies via its SAM domain. 25468754 6 10 theme S/T 857:859 arg1 stretch 861:867 the S/T stretch 853:867 the S/T stretch 853:867 We demonstrate that Ph mutants lacking the S/T stretch reproduce the phenotype of ogt mutants, suggesting that the S/T stretch in Ph is the key Ogt substrate in Drosophila. 25468754 7 11 theme functional 1044:1053 arg1 assemblies 1064:1073 functional, ordered assemblies 1044:1073 functional, ordered assemblies 1044:1073 We propose that O-GlcNAcylation is needed for Ph to form functional, ordered assemblies via its SAM domain. 25468754 1 12 theme glycosyltransferase 87:105 arg1 Ogt 107:109 The glycosyltransferase Ogt 83:109 The glycosyltransferase Ogt 83:109 The glycosyltransferase Ogt adds O-linked N-Acetylglucosamine (O-GlcNAc) moieties to nuclear and cytosolic proteins. 25468754 5 13 theme repressor 718:726 arg1 activity 728:735 Full Ph repressor activity 710:735 Full Ph repressor activity in vivo 710:743 Full Ph repressor activity in vivo requires both the SAM domain and O-GlcNAcylation of the S/T stretch. 25468754 2 14 theme target 350:355 arg1 genes 357:361 Polycomb target genes 341:361 Polycomb target genes 341:361 Drosophila embryos lacking Ogt protein arrest development with a remarkably specific Polycomb phenotype, arising from the failure to repress Polycomb target genes. 25468754 4 15 theme alpha 674:678 arg1 SAM 687:689 SAM 687:689 SAM 687:689 O-GlcNAcylation of a serine/threonine (S/T) stretch in Ph is critical to prevent nonproductive aggregation of both Drosophila and human Ph via their C-terminal sterile alpha motif (SAM) domains in vitro. 25468754 4 15 theme alpha 674:678 arg1 motif 680:684 C-terminal sterile alpha motif 655:684 their C-terminal sterile alpha motif (SAM) domains 649:698 O-GlcNAcylation of a serine/threonine (S/T) stretch in Ph is critical to prevent nonproductive aggregation of both Drosophila and human Ph via their C-terminal sterile alpha motif (SAM) domains in vitro. 25468754 3 16 theme Ogt 407:409 arg1 Polyhomeotic 385:396 The Polycomb protein Polyhomeotic 364:396 The Polycomb protein Polyhomeotic (Ph) 364:401 The Polycomb protein Polyhomeotic (Ph), an Ogt substrate, forms large aggregates in the absence of O-GlcNAcylation both in vivo and in vitro. 25468754 3 16 theme Ogt 407:409 arg1 substrate 411:419 an Ogt substrate 404:419 an Ogt substrate 404:419 The Polycomb protein Polyhomeotic (Ph), an Ogt substrate, forms large aggregates in the absence of O-GlcNAcylation both in vivo and in vitro. 25468754 6 17 theme mutants 900:906 arg1 phenotype 883:891 the phenotype 879:891 the phenotype of ogt mutants 879:906 We demonstrate that Ph mutants lacking the S/T stretch reproduce the phenotype of ogt mutants, suggesting that the S/T stretch in Ph is the key Ogt substrate in Drosophila. 25468754 2 18 theme Polycomb 341:348 arg1 genes 357:361 Polycomb target genes 341:361 Polycomb target genes 341:361 Drosophila embryos lacking Ogt protein arrest development with a remarkably specific Polycomb phenotype, arising from the failure to repress Polycomb target genes. 25468754 4 19 theme sterile 666:672 arg1 SAM 687:689 SAM 687:689 SAM 687:689 O-GlcNAcylation of a serine/threonine (S/T) stretch in Ph is critical to prevent nonproductive aggregation of both Drosophila and human Ph via their C-terminal sterile alpha motif (SAM) domains in vitro. 25468754 4 19 theme sterile 666:672 arg1 motif 680:684 C-terminal sterile alpha motif 655:684 their C-terminal sterile alpha motif (SAM) domains 649:698 O-GlcNAcylation of a serine/threonine (S/T) stretch in Ph is critical to prevent nonproductive aggregation of both Drosophila and human Ph via their C-terminal sterile alpha motif (SAM) domains in vitro. 25468754 4 20 theme stretch 550:556 arg1 O-GlcNAcylation 506:520 O-GlcNAcylation 506:520 O-GlcNAcylation of a serine/threonine (S/T) stretch in Ph 506:562 O-GlcNAcylation of a serine/threonine (S/T) stretch in Ph is critical to prevent nonproductive aggregation of both Drosophila and human Ph via their C-terminal sterile alpha motif (SAM) domains in vitro. 25468754 1 21 theme O-linked 116:123 arg1 O-GlcNAc 146:153 O-GlcNAc 146:153 O-GlcNAc 146:153 The glycosyltransferase Ogt adds O-linked N-Acetylglucosamine (O-GlcNAc) moieties to nuclear and cytosolic proteins. 25468754 1 21 theme O-linked 116:123 arg1 N-Acetylglucosamine 125:143 O-linked N-Acetylglucosamine 116:143 O-linked N-Acetylglucosamine (O-GlcNAc) moieties 116:163 The glycosyltransferase Ogt adds O-linked N-Acetylglucosamine (O-GlcNAc) moieties to nuclear and cytosolic proteins. 25468754 4 22 theme human 636:640 arg1 Ph 642:643 human Ph 636:643 human Ph 636:643 O-GlcNAcylation of a serine/threonine (S/T) stretch in Ph is critical to prevent nonproductive aggregation of both Drosophila and human Ph via their C-terminal sterile alpha motif (SAM) domains in vitro. 25468754 5 23 theme S/T 801:803 arg1 stretch 805:811 the S/T stretch 797:811 the S/T stretch 797:811 Full Ph repressor activity in vivo requires both the SAM domain and O-GlcNAcylation of the S/T stretch. 25468754 6 24 theme S/T 929:931 arg1 substrate 962:970 the key Ogt substrate 950:970 the key Ogt substrate in Drosophila 950:984 We demonstrate that Ph mutants lacking the S/T stretch reproduce the phenotype of ogt mutants, suggesting that the S/T stretch in Ph is the key Ogt substrate in Drosophila. 25468754 6 24 theme S/T 929:931 arg1 stretch 933:939 the S/T stretch 925:939 the S/T stretch in Ph 925:945 We demonstrate that Ph mutants lacking the S/T stretch reproduce the phenotype of ogt mutants, suggesting that the S/T stretch in Ph is the key Ogt substrate in Drosophila. 25468754 7 25 dep functional 1044:1053 arg1 ordered 1056:1062 ordered 1056:1062 ordered 1056:1062 We propose that O-GlcNAcylation is needed for Ph to form functional, ordered assemblies via its SAM domain. 25468754 1 26 theme N-Acetylglucosamine 125:143 arg1 moieties 156:163 O-linked N-Acetylglucosamine (O-GlcNAc) moieties 116:163 O-linked N-Acetylglucosamine (O-GlcNAc) moieties 116:163 The glycosyltransferase Ogt adds O-linked N-Acetylglucosamine (O-GlcNAc) moieties to nuclear and cytosolic proteins. 25468754 0 27 theme Polycomb 44:51 arg1 polyhomeotic 69:80 the Polycomb group repressor polyhomeotic 40:80 the Polycomb group repressor polyhomeotic 40:80 O-GlcNAcylation prevents aggregation of the Polycomb group repressor polyhomeotic. 25468754 2 28 theme Drosophila 200:209 arg1 embryos 211:217 Drosophila embryos 200:217 Drosophila embryos lacking Ogt protein 200:237 Drosophila embryos lacking Ogt protein arrest development with a remarkably specific Polycomb phenotype, arising from the failure to repress Polycomb target genes. 25468754 3 29 theme large 428:432 arg1 aggregates 434:443 large aggregates 428:443 large aggregates in the absence of O-GlcNAcylation 428:477 The Polycomb protein Polyhomeotic (Ph), an Ogt substrate, forms large aggregates in the absence of O-GlcNAcylation both in vivo and in vitro. 25468754 5 30 theme SAM 763:765 arg1 domain 767:772 the SAM domain 759:772 the SAM domain 759:772 Full Ph repressor activity in vivo requires both the SAM domain and O-GlcNAcylation of the S/T stretch. 25468754 5 30 theme SAM 763:765 arg1 stretch 805:811 the S/T stretch 797:811 the S/T stretch 797:811 Full Ph repressor activity in vivo requires both the SAM domain and O-GlcNAcylation of the S/T stretch. 25468754 6 31 theme Ph 834:835 arg1 mutants 837:843 Ph mutants 834:843 Ph mutants lacking the S/T stretch 834:867 We demonstrate that Ph mutants lacking the S/T stretch reproduce the phenotype of ogt mutants, suggesting that the S/T stretch in Ph is the key Ogt substrate in Drosophila. 25468754 6 32 from stretch 933:939 arg1 Ph 944:945 Ph 944:945 Ph 944:945 We demonstrate that Ph mutants lacking the S/T stretch reproduce the phenotype of ogt mutants, suggesting that the S/T stretch in Ph is the key Ogt substrate in Drosophila. 25468754 3 33 theme O-GlcNAcylation 463:477 arg1 absence 452:458 the absence 448:458 the absence of O-GlcNAcylation 448:477 The Polycomb protein Polyhomeotic (Ph), an Ogt substrate, forms large aggregates in the absence of O-GlcNAcylation both in vivo and in vitro. 25468754 0 34 theme repressor 59:67 arg1 polyhomeotic 69:80 the Polycomb group repressor polyhomeotic 40:80 the Polycomb group repressor polyhomeotic 40:80 O-GlcNAcylation prevents aggregation of the Polycomb group repressor polyhomeotic. 25468754 4 35 theme serine/threonine 527:542 arg1 stretch 550:556 a serine/threonine (S/T) stretch 525:556 a serine/threonine (S/T) stretch 525:556 O-GlcNAcylation of a serine/threonine (S/T) stretch in Ph is critical to prevent nonproductive aggregation of both Drosophila and human Ph via their C-terminal sterile alpha motif (SAM) domains in vitro. 25468754 0 36 theme polyhomeotic 69:80 arg1 aggregation 25:35 aggregation 25:35 aggregation of the Polycomb group repressor polyhomeotic 25:80 O-GlcNAcylation prevents aggregation of the Polycomb group repressor polyhomeotic. 25468754 0 37 theme group 53:57 arg1 polyhomeotic 69:80 the Polycomb group repressor polyhomeotic 40:80 the Polycomb group repressor polyhomeotic 40:80 O-GlcNAcylation prevents aggregation of the Polycomb group repressor polyhomeotic. 25468754 4 38 theme S/T 545:547 arg1 stretch 550:556 a serine/threonine (S/T) stretch 525:556 a serine/threonine (S/T) stretch 525:556 O-GlcNAcylation of a serine/threonine (S/T) stretch in Ph is critical to prevent nonproductive aggregation of both Drosophila and human Ph via their C-terminal sterile alpha motif (SAM) domains in vitro. 25468754 2 39 theme Ogt 227:229 arg1 protein 231:237 Ogt protein 227:237 Ogt protein 227:237 Drosophila embryos lacking Ogt protein arrest development with a remarkably specific Polycomb phenotype, arising from the failure to repress Polycomb target genes. 25468754 3 40 from aggregates 434:443 arg1 absence 452:458 the absence 448:458 the absence of O-GlcNAcylation 448:477 The Polycomb protein Polyhomeotic (Ph), an Ogt substrate, forms large aggregates in the absence of O-GlcNAcylation both in vivo and in vitro. 25468754 4 41 theme motif 680:684 arg1 domains 692:698 their C-terminal sterile alpha motif (SAM) domains 649:698 their C-terminal sterile alpha motif (SAM) domains 649:698 O-GlcNAcylation of a serine/threonine (S/T) stretch in Ph is critical to prevent nonproductive aggregation of both Drosophila and human Ph via their C-terminal sterile alpha motif (SAM) domains in vitro. 25468754 1 42 link O-linked 116:123 arg1 O-GlcNAc 146:153 O-GlcNAc 146:153 O-GlcNAc 146:153 The glycosyltransferase Ogt adds O-linked N-Acetylglucosamine (O-GlcNAc) moieties to nuclear and cytosolic proteins. 25468754 1 42 link O-linked 116:123 arg1 N-Acetylglucosamine 125:143 O-linked N-Acetylglucosamine 116:143 O-linked N-Acetylglucosamine (O-GlcNAc) moieties 116:163 The glycosyltransferase Ogt adds O-linked N-Acetylglucosamine (O-GlcNAc) moieties to nuclear and cytosolic proteins. 25468754 4 43 theme Ph 642:643 arg1 aggregation 601:611 nonproductive aggregation 587:611 nonproductive aggregation of both Drosophila and human Ph 587:643 O-GlcNAcylation of a serine/threonine (S/T) stretch in Ph is critical to prevent nonproductive aggregation of both Drosophila and human Ph via their C-terminal sterile alpha motif (SAM) domains in vitro. 25468754 2 44 theme Polycomb 285:292 arg1 phenotype 294:302 a remarkably specific Polycomb phenotype 263:302 a remarkably specific Polycomb phenotype 263:302 Drosophila embryos lacking Ogt protein arrest development with a remarkably specific Polycomb phenotype, arising from the failure to repress Polycomb target genes. 25468754 5 45 theme stretch 805:811 arg1 domain 767:772 the SAM domain 759:772 the SAM domain 759:772 Full Ph repressor activity in vivo requires both the SAM domain and O-GlcNAcylation of the S/T stretch. 25468754 5 45 theme stretch 805:811 arg1 stretch 805:811 the S/T stretch 797:811 the S/T stretch 797:811 Full Ph repressor activity in vivo requires both the SAM domain and O-GlcNAcylation of the S/T stretch. 25468754 5 45 theme stretch 805:811 arg1 O-GlcNAcylation 778:792 O-GlcNAcylation 778:792 O-GlcNAcylation 778:792 Full Ph repressor activity in vivo requires both the SAM domain and O-GlcNAcylation of the S/T stretch. 25468754 4 46 theme Drosophila 621:630 arg1 aggregation 601:611 nonproductive aggregation 587:611 nonproductive aggregation of both Drosophila and human Ph 587:643 O-GlcNAcylation of a serine/threonine (S/T) stretch in Ph is critical to prevent nonproductive aggregation of both Drosophila and human Ph via their C-terminal sterile alpha motif (SAM) domains in vitro. 25468754 3 47 theme Polycomb 368:375 arg1 Polyhomeotic 385:396 The Polycomb protein Polyhomeotic 364:396 The Polycomb protein Polyhomeotic (Ph) 364:401 The Polycomb protein Polyhomeotic (Ph), an Ogt substrate, forms large aggregates in the absence of O-GlcNAcylation both in vivo and in vitro. 25468754 3 47 theme Polycomb 368:375 arg1 substrate 411:419 an Ogt substrate 404:419 an Ogt substrate 404:419 The Polycomb protein Polyhomeotic (Ph), an Ogt substrate, forms large aggregates in the absence of O-GlcNAcylation both in vivo and in vitro. 25468754 3 47 theme Polycomb 368:375 arg1 Ph 399:400 Ph 399:400 Ph 399:400 The Polycomb protein Polyhomeotic (Ph), an Ogt substrate, forms large aggregates in the absence of O-GlcNAcylation both in vivo and in vitro. 25468754 6 48 theme ogt 896:898 arg1 mutants 900:906 ogt mutants 896:906 ogt mutants 896:906 We demonstrate that Ph mutants lacking the S/T stretch reproduce the phenotype of ogt mutants, suggesting that the S/T stretch in Ph is the key Ogt substrate in Drosophila. 25468754 2 49 theme specific 276:283 arg1 phenotype 294:302 a remarkably specific Polycomb phenotype 263:302 a remarkably specific Polycomb phenotype 263:302 Drosophila embryos lacking Ogt protein arrest development with a remarkably specific Polycomb phenotype, arising from the failure to repress Polycomb target genes. 25468754 1 50 theme nuclear 168:174 arg1 proteins 190:197 nuclear and cytosolic proteins 168:197 nuclear and cytosolic proteins 168:197 The glycosyltransferase Ogt adds O-linked N-Acetylglucosamine (O-GlcNAc) moieties to nuclear and cytosolic proteins. 25468754 6 51 theme Ogt 958:960 arg1 substrate 962:970 the key Ogt substrate 950:970 the key Ogt substrate in Drosophila 950:984 We demonstrate that Ph mutants lacking the S/T stretch reproduce the phenotype of ogt mutants, suggesting that the S/T stretch in Ph is the key Ogt substrate in Drosophila. 25468754 6 51 theme Ogt 958:960 arg1 stretch 933:939 the S/T stretch 925:939 the S/T stretch in Ph 925:945 We demonstrate that Ph mutants lacking the S/T stretch reproduce the phenotype of ogt mutants, suggesting that the S/T stretch in Ph is the key Ogt substrate in Drosophila. 25313651 5 0 theme sialylated 814:823 arg1 glycans 825:831 the cardiac sialylated glycans 802:831 the cardiac sialylated glycans 802:831 We demonstrated this methodology by visualization of the cardiac sialylated glycans in intact hearts and identification of more than 200 cardiac proteins modified with sialic acids. 25313651 3 1 from azidosugars 453:463 arg1 rats 475:478 living rats 468:478 living rats 468:478 Here we describe a chemical approach for analyzing the dynamic cardiac glycome by metabolically labeling the cardiac glycans with azidosugars in living rats. 25313651 4 2 theme proteins 739:746 arg1 enrichment 675:684 enrichment 675:684 enrichment 675:684 The azides, serving as a chemical reporter, are chemoselectively conjugated with fluorophores using copper-free click chemistry for glycan imaging; derivatizing azides with affinity tags allows enrichment and proteomic identification of glycosylated cardiac proteins. 25313651 4 2 theme proteins 739:746 arg1 identification 700:713 proteomic identification 690:713 proteomic identification 690:713 The azides, serving as a chemical reporter, are chemoselectively conjugated with fluorophores using copper-free click chemistry for glycan imaging; derivatizing azides with affinity tags allows enrichment and proteomic identification of glycosylated cardiac proteins. 25313651 5 3 theme glycans 825:831 arg1 visualization 785:797 visualization 785:797 visualization of the cardiac sialylated glycans in intact hearts 785:848 We demonstrated this methodology by visualization of the cardiac sialylated glycans in intact hearts and identification of more than 200 cardiac proteins modified with sialic acids. 25313651 5 3 theme glycans 825:831 arg1 identification 854:867 identification 854:867 identification of more than 200 cardiac proteins modified with sialic acids 854:928 We demonstrated this methodology by visualization of the cardiac sialylated glycans in intact hearts and identification of more than 200 cardiac proteins modified with sialic acids. 25313651 0 4 from imaging 7:13 arg1 hearts 29:34 intact rat hearts 18:34 intact rat hearts 18:34 Glycan imaging in intact rat hearts and glycoproteomic analysis reveal the upregulation of sialylation during cardiac hypertrophy. 25313651 8 5 theme proteomic 1147:1155 arg1 analysis 1157:1164 Quantitative proteomic analysis 1134:1164 Quantitative proteomic analysis 1134:1164 Quantitative proteomic analysis identified multiple sialylated proteins including neural cell adhesion molecule 1, T-kininogens, and α2-macroglobulin that were upregulated during hypertrophy. 25313651 7 6 theme imaging 1026:1032 arg1 results 1034:1040 The imaging results 1022:1040 The imaging results 1022:1040 The imaging results revealed an increase of sialic acid biosynthesis upon the induction of cardiac hypertrophy. 25313651 4 7 theme cardiac 731:737 arg1 proteins 739:746 glycosylated cardiac proteins 718:746 glycosylated cardiac proteins 718:746 The azides, serving as a chemical reporter, are chemoselectively conjugated with fluorophores using copper-free click chemistry for glycan imaging; derivatizing azides with affinity tags allows enrichment and proteomic identification of glycosylated cardiac proteins. 25313651 10 8 theme pathophysiological 1628:1645 arg1 responses 1647:1655 pathophysiological responses 1628:1655 pathophysiological responses 1628:1655 Our results highlight the applications of metabolic glycan labeling coupled with bioorthogonal chemistry in probing the biosynthesis and function of cardiac glycome during pathophysiological responses. 25313651 4 9 theme click 593:597 arg1 chemistry 599:607 copper-free click chemistry 581:607 copper-free click chemistry for glycan imaging 581:626 The azides, serving as a chemical reporter, are chemoselectively conjugated with fluorophores using copper-free click chemistry for glycan imaging; derivatizing azides with affinity tags allows enrichment and proteomic identification of glycosylated cardiac proteins. 25313651 0 10 theme sialylation 91:101 arg1 upregulation 75:86 the upregulation 71:86 the upregulation of sialylation during cardiac hypertrophy 71:128 Glycan imaging in intact rat hearts and glycoproteomic analysis reveal the upregulation of sialylation during cardiac hypertrophy. 25313651 4 11 theme chemical 506:513 arg1 reporter 515:522 a chemical reporter 504:522 a chemical reporter 504:522 The azides, serving as a chemical reporter, are chemoselectively conjugated with fluorophores using copper-free click chemistry for glycan imaging; derivatizing azides with affinity tags allows enrichment and proteomic identification of glycosylated cardiac proteins. 25313651 10 12 theme glycan 1508:1513 arg1 labeling 1515:1522 metabolic glycan labeling 1498:1522 metabolic glycan labeling coupled with bioorthogonal chemistry 1498:1559 Our results highlight the applications of metabolic glycan labeling coupled with bioorthogonal chemistry in probing the biosynthesis and function of cardiac glycome during pathophysiological responses. 25313651 4 13 theme glycan 613:618 arg1 imaging 620:626 glycan imaging 613:626 glycan imaging 613:626 The azides, serving as a chemical reporter, are chemoselectively conjugated with fluorophores using copper-free click chemistry for glycan imaging; derivatizing azides with affinity tags allows enrichment and proteomic identification of glycosylated cardiac proteins. 25313651 6 14 gly sialylation 986:996 arg1 hearts 1014:1019 hypertrophic hearts 1001:1019 hypertrophic hearts 1001:1019 We further applied this methodology to investigate the sialylation in hypertrophic hearts. 25313651 8 15 gly sialylated 1186:1195 arg1 T-kininogens 1249:1260 T-kininogens 1249:1260 T-kininogens 1249:1260 Quantitative proteomic analysis identified multiple sialylated proteins including neural cell adhesion molecule 1, T-kininogens, and α2-macroglobulin that were upregulated during hypertrophy. 25313651 8 15 gly sialylated 1186:1195 arg1 molecule 1237:1244 neural cell adhesion molecule 1 1216:1246 neural cell adhesion molecule 1 1216:1246 Quantitative proteomic analysis identified multiple sialylated proteins including neural cell adhesion molecule 1, T-kininogens, and α2-macroglobulin that were upregulated during hypertrophy. 25313651 8 15 gly sialylated 1186:1195 arg1 proteins 1197:1204 multiple sialylated proteins 1177:1204 multiple sialylated proteins including neural cell adhesion molecule 1, T-kininogens, and α2-macroglobulin that were upregulated during hypertrophy 1177:1323 Quantitative proteomic analysis identified multiple sialylated proteins including neural cell adhesion molecule 1, T-kininogens, and α2-macroglobulin that were upregulated during hypertrophy. 25313651 8 15 gly sialylated 1186:1195 arg1 α2-macroglobulin 1267:1282 α2-macroglobulin 1267:1282 α2-macroglobulin 1267:1282 Quantitative proteomic analysis identified multiple sialylated proteins including neural cell adhesion molecule 1, T-kininogens, and α2-macroglobulin that were upregulated during hypertrophy. 25313651 3 16 theme chemical 342:349 arg1 approach 351:358 a chemical approach 340:358 a chemical approach for analyzing the dynamic cardiac glycome 340:400 Here we describe a chemical approach for analyzing the dynamic cardiac glycome by metabolically labeling the cardiac glycans with azidosugars in living rats. 25313651 10 17 theme glycome 1613:1619 arg1 biosynthesis 1576:1587 biosynthesis 1576:1587 biosynthesis 1576:1587 Our results highlight the applications of metabolic glycan labeling coupled with bioorthogonal chemistry in probing the biosynthesis and function of cardiac glycome during pathophysiological responses. 25313651 10 17 theme glycome 1613:1619 arg1 function 1593:1600 function 1593:1600 function 1593:1600 Our results highlight the applications of metabolic glycan labeling coupled with bioorthogonal chemistry in probing the biosynthesis and function of cardiac glycome during pathophysiological responses. 25313651 5 18 theme cardiac 886:892 arg1 proteins 894:901 more than 200 cardiac proteins 872:901 more than 200 cardiac proteins modified with sialic acids 872:928 We demonstrated this methodology by visualization of the cardiac sialylated glycans in intact hearts and identification of more than 200 cardiac proteins modified with sialic acids. 25313651 9 19 link O-linked 1432:1439 arg1 glycosylation 1441:1453 the mucin-type O-linked glycosylation 1417:1453 the mucin-type O-linked glycosylation 1417:1453 The methodology may be further extended to other types of glycosylation, as exemplified by the mucin-type O-linked glycosylation. 25313651 10 20 dep biosynthesis 1576:1587 arg1 the 1572:1574 the 1572:1574 the 1572:1574 Our results highlight the applications of metabolic glycan labeling coupled with bioorthogonal chemistry in probing the biosynthesis and function of cardiac glycome during pathophysiological responses. 25313651 5 21 from identification 854:867 arg1 hearts 843:848 intact hearts 836:848 intact hearts 836:848 We demonstrated this methodology by visualization of the cardiac sialylated glycans in intact hearts and identification of more than 200 cardiac proteins modified with sialic acids. 25313651 10 22 theme cardiac 1605:1611 arg1 glycome 1613:1619 cardiac glycome 1605:1619 cardiac glycome 1605:1619 Our results highlight the applications of metabolic glycan labeling coupled with bioorthogonal chemistry in probing the biosynthesis and function of cardiac glycome during pathophysiological responses. 25313651 5 23 gly sialylated 814:823 arg1 glycans 825:831 the cardiac sialylated glycans 802:831 the cardiac sialylated glycans 802:831 We demonstrated this methodology by visualization of the cardiac sialylated glycans in intact hearts and identification of more than 200 cardiac proteins modified with sialic acids. 25313651 8 24 theme sialylated 1186:1195 arg1 T-kininogens 1249:1260 T-kininogens 1249:1260 T-kininogens 1249:1260 Quantitative proteomic analysis identified multiple sialylated proteins including neural cell adhesion molecule 1, T-kininogens, and α2-macroglobulin that were upregulated during hypertrophy. 25313651 8 24 theme sialylated 1186:1195 arg1 molecule 1237:1244 neural cell adhesion molecule 1 1216:1246 neural cell adhesion molecule 1 1216:1246 Quantitative proteomic analysis identified multiple sialylated proteins including neural cell adhesion molecule 1, T-kininogens, and α2-macroglobulin that were upregulated during hypertrophy. 25313651 8 24 theme sialylated 1186:1195 arg1 proteins 1197:1204 multiple sialylated proteins 1177:1204 multiple sialylated proteins including neural cell adhesion molecule 1, T-kininogens, and α2-macroglobulin that were upregulated during hypertrophy 1177:1323 Quantitative proteomic analysis identified multiple sialylated proteins including neural cell adhesion molecule 1, T-kininogens, and α2-macroglobulin that were upregulated during hypertrophy. 25313651 8 24 theme sialylated 1186:1195 arg1 α2-macroglobulin 1267:1282 α2-macroglobulin 1267:1282 α2-macroglobulin 1267:1282 Quantitative proteomic analysis identified multiple sialylated proteins including neural cell adhesion molecule 1, T-kininogens, and α2-macroglobulin that were upregulated during hypertrophy. 25313651 0 25 theme cardiac 110:116 arg1 hypertrophy 118:128 cardiac hypertrophy 110:128 cardiac hypertrophy 110:128 Glycan imaging in intact rat hearts and glycoproteomic analysis reveal the upregulation of sialylation during cardiac hypertrophy. 25313651 3 26 theme cardiac 386:392 arg1 glycome 394:400 the dynamic cardiac glycome 374:400 the dynamic cardiac glycome 374:400 Here we describe a chemical approach for analyzing the dynamic cardiac glycome by metabolically labeling the cardiac glycans with azidosugars in living rats. 25313651 9 27 theme O-linked 1432:1439 arg1 glycosylation 1441:1453 the mucin-type O-linked glycosylation 1417:1453 the mucin-type O-linked glycosylation 1417:1453 The methodology may be further extended to other types of glycosylation, as exemplified by the mucin-type O-linked glycosylation. 25313651 7 28 theme cardiac 1113:1119 arg1 hypertrophy 1121:1131 cardiac hypertrophy 1113:1131 cardiac hypertrophy 1113:1131 The imaging results revealed an increase of sialic acid biosynthesis upon the induction of cardiac hypertrophy. 25313651 6 29 from sialylation 986:996 arg1 hearts 1014:1019 hypertrophic hearts 1001:1019 hypertrophic hearts 1001:1019 We further applied this methodology to investigate the sialylation in hypertrophic hearts. 25313651 3 30 theme cardiac 432:438 arg1 glycans 440:446 the cardiac glycans 428:446 the cardiac glycans 428:446 Here we describe a chemical approach for analyzing the dynamic cardiac glycome by metabolically labeling the cardiac glycans with azidosugars in living rats. 25313651 0 31 theme Glycan 0:5 arg1 imaging 7:13 Glycan imaging 0:13 Glycan imaging in intact rat hearts 0:34 Glycan imaging in intact rat hearts and glycoproteomic analysis reveal the upregulation of sialylation during cardiac hypertrophy. 25313651 8 32 theme Quantitative 1134:1145 arg1 analysis 1157:1164 Quantitative proteomic analysis 1134:1164 Quantitative proteomic analysis 1134:1164 Quantitative proteomic analysis identified multiple sialylated proteins including neural cell adhesion molecule 1, T-kininogens, and α2-macroglobulin that were upregulated during hypertrophy. 25313651 10 33 theme bioorthogonal 1537:1549 arg1 chemistry 1551:1559 bioorthogonal chemistry 1537:1559 bioorthogonal chemistry 1537:1559 Our results highlight the applications of metabolic glycan labeling coupled with bioorthogonal chemistry in probing the biosynthesis and function of cardiac glycome during pathophysiological responses. 25313651 4 34 theme proteomic 690:698 arg1 identification 700:713 proteomic identification 690:713 proteomic identification 690:713 The azides, serving as a chemical reporter, are chemoselectively conjugated with fluorophores using copper-free click chemistry for glycan imaging; derivatizing azides with affinity tags allows enrichment and proteomic identification of glycosylated cardiac proteins. 25313651 0 35 theme intact 18:23 arg1 hearts 29:34 intact rat hearts 18:34 intact rat hearts 18:34 Glycan imaging in intact rat hearts and glycoproteomic analysis reveal the upregulation of sialylation during cardiac hypertrophy. 25313651 10 36 theme metabolic 1498:1506 arg1 labeling 1515:1522 metabolic glycan labeling 1498:1522 metabolic glycan labeling coupled with bioorthogonal chemistry 1498:1559 Our results highlight the applications of metabolic glycan labeling coupled with bioorthogonal chemistry in probing the biosynthesis and function of cardiac glycome during pathophysiological responses. 25313651 4 37 theme affinity 654:661 arg1 tags 663:666 affinity tags 654:666 affinity tags 654:666 The azides, serving as a chemical reporter, are chemoselectively conjugated with fluorophores using copper-free click chemistry for glycan imaging; derivatizing azides with affinity tags allows enrichment and proteomic identification of glycosylated cardiac proteins. 25313651 3 38 theme dynamic 378:384 arg1 glycome 394:400 the dynamic cardiac glycome 374:400 the dynamic cardiac glycome 374:400 Here we describe a chemical approach for analyzing the dynamic cardiac glycome by metabolically labeling the cardiac glycans with azidosugars in living rats. 25313651 4 39 theme copper-free 581:591 arg1 chemistry 599:607 copper-free click chemistry 581:607 copper-free click chemistry for glycan imaging 581:626 The azides, serving as a chemical reporter, are chemoselectively conjugated with fluorophores using copper-free click chemistry for glycan imaging; derivatizing azides with affinity tags allows enrichment and proteomic identification of glycosylated cardiac proteins. 25313651 5 40 from visualization 785:797 arg1 hearts 843:848 intact hearts 836:848 intact hearts 836:848 We demonstrated this methodology by visualization of the cardiac sialylated glycans in intact hearts and identification of more than 200 cardiac proteins modified with sialic acids. 25313651 1 41 theme physiological 187:199 arg1 processes 218:226 physiological and pathological processes 187:226 physiological and pathological processes 187:226 In the heart, glycosylation is involved in a variety of physiological and pathological processes. 25313651 7 42 theme hypertrophy 1121:1131 arg1 induction 1100:1108 the induction 1096:1108 the induction of cardiac hypertrophy 1096:1131 The imaging results revealed an increase of sialic acid biosynthesis upon the induction of cardiac hypertrophy. 25313651 4 43 with azides 642:647 arg1 tags 663:666 affinity tags 654:666 affinity tags 654:666 The azides, serving as a chemical reporter, are chemoselectively conjugated with fluorophores using copper-free click chemistry for glycan imaging; derivatizing azides with affinity tags allows enrichment and proteomic identification of glycosylated cardiac proteins. 25313651 5 44 theme proteins 894:901 arg1 visualization 785:797 visualization 785:797 visualization of the cardiac sialylated glycans in intact hearts 785:848 We demonstrated this methodology by visualization of the cardiac sialylated glycans in intact hearts and identification of more than 200 cardiac proteins modified with sialic acids. 25313651 5 44 theme proteins 894:901 arg1 identification 854:867 identification 854:867 identification of more than 200 cardiac proteins modified with sialic acids 854:928 We demonstrated this methodology by visualization of the cardiac sialylated glycans in intact hearts and identification of more than 200 cardiac proteins modified with sialic acids. 25313651 0 45 theme rat 25:27 arg1 hearts 29:34 intact rat hearts 18:34 intact rat hearts 18:34 Glycan imaging in intact rat hearts and glycoproteomic analysis reveal the upregulation of sialylation during cardiac hypertrophy. 25313651 5 46 theme intact 836:841 arg1 hearts 843:848 intact hearts 836:848 intact hearts 836:848 We demonstrated this methodology by visualization of the cardiac sialylated glycans in intact hearts and identification of more than 200 cardiac proteins modified with sialic acids. 25313651 2 47 theme Cardiac 229:235 arg1 glycosylation 237:249 Cardiac glycosylation 229:249 Cardiac glycosylation 229:249 Cardiac glycosylation is dynamically regulated, which remains challenging to monitor in vivo. 25313651 7 48 theme biosynthesis 1078:1089 arg1 increase 1054:1061 an increase 1051:1061 an increase of sialic acid biosynthesis upon the induction of cardiac hypertrophy 1051:1131 The imaging results revealed an increase of sialic acid biosynthesis upon the induction of cardiac hypertrophy. 25313651 1 49 theme pathological 205:216 arg1 processes 218:226 physiological and pathological processes 187:226 physiological and pathological processes 187:226 In the heart, glycosylation is involved in a variety of physiological and pathological processes. 25313651 0 50 theme glycoproteomic 40:53 arg1 analysis 55:62 glycoproteomic analysis 40:62 glycoproteomic analysis 40:62 Glycan imaging in intact rat hearts and glycoproteomic analysis reveal the upregulation of sialylation during cardiac hypertrophy. 25313651 6 51 theme hypertrophic 1001:1012 arg1 hearts 1014:1019 hypertrophic hearts 1001:1019 hypertrophic hearts 1001:1019 We further applied this methodology to investigate the sialylation in hypertrophic hearts. 25313651 0 52 from analysis 55:62 arg1 hearts 29:34 intact rat hearts 18:34 intact rat hearts 18:34 Glycan imaging in intact rat hearts and glycoproteomic analysis reveal the upregulation of sialylation during cardiac hypertrophy. 25313651 9 53 theme mucin-type 1421:1430 arg1 glycosylation 1441:1453 the mucin-type O-linked glycosylation 1417:1453 the mucin-type O-linked glycosylation 1417:1453 The methodology may be further extended to other types of glycosylation, as exemplified by the mucin-type O-linked glycosylation. 25313651 8 54 theme multiple 1177:1184 arg1 T-kininogens 1249:1260 T-kininogens 1249:1260 T-kininogens 1249:1260 Quantitative proteomic analysis identified multiple sialylated proteins including neural cell adhesion molecule 1, T-kininogens, and α2-macroglobulin that were upregulated during hypertrophy. 25313651 8 54 theme multiple 1177:1184 arg1 molecule 1237:1244 neural cell adhesion molecule 1 1216:1246 neural cell adhesion molecule 1 1216:1246 Quantitative proteomic analysis identified multiple sialylated proteins including neural cell adhesion molecule 1, T-kininogens, and α2-macroglobulin that were upregulated during hypertrophy. 25313651 8 54 theme multiple 1177:1184 arg1 proteins 1197:1204 multiple sialylated proteins 1177:1204 multiple sialylated proteins including neural cell adhesion molecule 1, T-kininogens, and α2-macroglobulin that were upregulated during hypertrophy 1177:1323 Quantitative proteomic analysis identified multiple sialylated proteins including neural cell adhesion molecule 1, T-kininogens, and α2-macroglobulin that were upregulated during hypertrophy. 25313651 8 54 theme multiple 1177:1184 arg1 α2-macroglobulin 1267:1282 α2-macroglobulin 1267:1282 α2-macroglobulin 1267:1282 Quantitative proteomic analysis identified multiple sialylated proteins including neural cell adhesion molecule 1, T-kininogens, and α2-macroglobulin that were upregulated during hypertrophy. 25313651 10 55 theme labeling 1515:1522 arg1 applications 1482:1493 the applications 1478:1493 the applications of metabolic glycan labeling coupled with bioorthogonal chemistry 1478:1559 Our results highlight the applications of metabolic glycan labeling coupled with bioorthogonal chemistry in probing the biosynthesis and function of cardiac glycome during pathophysiological responses. 25313651 4 56 gly glycosylated 718:729 arg1 proteins 739:746 glycosylated cardiac proteins 718:746 glycosylated cardiac proteins 718:746 The azides, serving as a chemical reporter, are chemoselectively conjugated with fluorophores using copper-free click chemistry for glycan imaging; derivatizing azides with affinity tags allows enrichment and proteomic identification of glycosylated cardiac proteins. 25313651 7 57 theme sialic 1066:1071 arg1 biosynthesis 1078:1089 sialic acid biosynthesis 1066:1089 sialic acid biosynthesis 1066:1089 The imaging results revealed an increase of sialic acid biosynthesis upon the induction of cardiac hypertrophy. 25313651 8 58 theme cell 1223:1226 arg1 molecule 1237:1244 neural cell adhesion molecule 1 1216:1246 neural cell adhesion molecule 1 1216:1246 Quantitative proteomic analysis identified multiple sialylated proteins including neural cell adhesion molecule 1, T-kininogens, and α2-macroglobulin that were upregulated during hypertrophy. 25313651 9 59 theme other 1369:1373 arg1 types 1375:1379 other types 1369:1379 other types of glycosylation 1369:1396 The methodology may be further extended to other types of glycosylation, as exemplified by the mucin-type O-linked glycosylation. 25313651 7 60 theme acid 1073:1076 arg1 biosynthesis 1078:1089 sialic acid biosynthesis 1066:1089 sialic acid biosynthesis 1066:1089 The imaging results revealed an increase of sialic acid biosynthesis upon the induction of cardiac hypertrophy. 25313651 1 61 theme processes 218:226 arg1 processes 218:226 physiological and pathological processes 187:226 physiological and pathological processes 187:226 In the heart, glycosylation is involved in a variety of physiological and pathological processes. 25313651 1 61 theme processes 218:226 arg1 variety 176:182 a variety 174:182 a variety of physiological and pathological processes 174:226 In the heart, glycosylation is involved in a variety of physiological and pathological processes. 25313651 1 62 gly glycosylation 145:157 arg1 processes 218:226 physiological and pathological processes 187:226 physiological and pathological processes 187:226 In the heart, glycosylation is involved in a variety of physiological and pathological processes. 25313651 1 62 gly glycosylation 145:157 arg1 variety 176:182 a variety 174:182 a variety of physiological and pathological processes 174:226 In the heart, glycosylation is involved in a variety of physiological and pathological processes. 25313651 1 62 gly glycosylation 145:157 arg1 heart 138:142 the heart 134:142 the heart 134:142 In the heart, glycosylation is involved in a variety of physiological and pathological processes. 25313651 8 63 theme adhesion 1228:1235 arg1 molecule 1237:1244 neural cell adhesion molecule 1 1216:1246 neural cell adhesion molecule 1 1216:1246 Quantitative proteomic analysis identified multiple sialylated proteins including neural cell adhesion molecule 1, T-kininogens, and α2-macroglobulin that were upregulated during hypertrophy. 25313651 3 64 theme living 468:473 arg1 rats 475:478 living rats 468:478 living rats 468:478 Here we describe a chemical approach for analyzing the dynamic cardiac glycome by metabolically labeling the cardiac glycans with azidosugars in living rats. 25313651 4 65 theme glycosylated 718:729 arg1 proteins 739:746 glycosylated cardiac proteins 718:746 glycosylated cardiac proteins 718:746 The azides, serving as a chemical reporter, are chemoselectively conjugated with fluorophores using copper-free click chemistry for glycan imaging; derivatizing azides with affinity tags allows enrichment and proteomic identification of glycosylated cardiac proteins. 25313651 5 66 theme sialic 917:922 arg1 acids 924:928 sialic acids 917:928 sialic acids 917:928 We demonstrated this methodology by visualization of the cardiac sialylated glycans in intact hearts and identification of more than 200 cardiac proteins modified with sialic acids. 25313651 5 67 theme cardiac 806:812 arg1 glycans 825:831 the cardiac sialylated glycans 802:831 the cardiac sialylated glycans 802:831 We demonstrated this methodology by visualization of the cardiac sialylated glycans in intact hearts and identification of more than 200 cardiac proteins modified with sialic acids. 25313651 9 68 theme glycosylation 1384:1396 arg1 types 1375:1379 other types 1369:1379 other types of glycosylation 1369:1396 The methodology may be further extended to other types of glycosylation, as exemplified by the mucin-type O-linked glycosylation. 25313651 8 69 theme neural 1216:1221 arg1 molecule 1237:1244 neural cell adhesion molecule 1 1216:1246 neural cell adhesion molecule 1 1216:1246 Quantitative proteomic analysis identified multiple sialylated proteins including neural cell adhesion molecule 1, T-kininogens, and α2-macroglobulin that were upregulated during hypertrophy. 25313651 4 70 theme derivatizing 629:640 arg1 azides 642:647 derivatizing azides 629:647 derivatizing azides with affinity tags 629:666 The azides, serving as a chemical reporter, are chemoselectively conjugated with fluorophores using copper-free click chemistry for glycan imaging; derivatizing azides with affinity tags allows enrichment and proteomic identification of glycosylated cardiac proteins. 25556750 2 0 theme xanthine 471:478 arg1 oxidase 480:486 xanthine oxidase 471:486 xanthine oxidase (X-XO) 471:493 Spermatozoa were exposed to different concentrations of xanthine and xanthine oxidase (X-XO) either in the presence or absence of antioxidants for 15 and 60 min. 25556750 2 0 theme xanthine 471:478 arg1 X-XO 489:492 X-XO 489:492 X-XO 489:492 Spermatozoa were exposed to different concentrations of xanthine and xanthine oxidase (X-XO) either in the presence or absence of antioxidants for 15 and 60 min. 25556750 1 1 theme tyrosine 307:314 arg1 phosphorylation 316:330 protein tyrosine phosphorylation 299:330 protein tyrosine phosphorylation in spermatozoa of the common carp (Cyprinus carpio) 299:382 The effect of reactive oxygen species production on the motility parameters, DNA integrity, acid phosphatase activity, and protein tyrosine phosphorylation in spermatozoa of the common carp (Cyprinus carpio) was investigated. 25556750 1 1 theme tyrosine 307:314 arg1 parameters 241:250 the motility parameters 228:250 the motility parameters 228:250 The effect of reactive oxygen species production on the motility parameters, DNA integrity, acid phosphatase activity, and protein tyrosine phosphorylation in spermatozoa of the common carp (Cyprinus carpio) was investigated. 25556750 2 2 dep concentrations 440:453 arg1 either 495:500 either 495:500 either 495:500 Spermatozoa were exposed to different concentrations of xanthine and xanthine oxidase (X-XO) either in the presence or absence of antioxidants for 15 and 60 min. 25556750 8 3 dep variables 1242:1250 arg1 velocity 1269:1276 velocity 1269:1276 velocity 1269:1276 The results demonstrate that oxidative stress impaired functional variables (sperm motility, velocity, DNA integrity) of carp spermatozoa, and altered intracellular signalling pathways through changes in tyrosine phosphorylation and acid phosphatase activity. 25556750 8 3 dep variables 1242:1250 arg1 integrity 1283:1291 DNA integrity 1279:1291 DNA integrity 1279:1291 The results demonstrate that oxidative stress impaired functional variables (sperm motility, velocity, DNA integrity) of carp spermatozoa, and altered intracellular signalling pathways through changes in tyrosine phosphorylation and acid phosphatase activity. 25556750 8 3 dep variables 1242:1250 arg1 motility 1259:1266 sperm motility 1253:1266 sperm motility 1253:1266 The results demonstrate that oxidative stress impaired functional variables (sperm motility, velocity, DNA integrity) of carp spermatozoa, and altered intracellular signalling pathways through changes in tyrosine phosphorylation and acid phosphatase activity. 25556750 0 4 theme DNA 62:64 arg1 integrity 66:74 DNA integrity 62:74 DNA integrity 62:74 The effect of reactive oxygen species on motility parameters, DNA integrity, tyrosine phosphorylation and phosphatase activity of common carp (Cyprinus carpio L.) spermatozoa. 25556750 0 4 theme DNA 62:64 arg1 effect 4:9 The effect 0:9 The effect of reactive oxygen species on motility parameters 0:59 The effect of reactive oxygen species on motility parameters, DNA integrity, tyrosine phosphorylation and phosphatase activity of common carp (Cyprinus carpio L.) spermatozoa. 25556750 0 5 from effect 4:9 arg1 parameters 50:59 motility parameters 41:59 motility parameters 41:59 The effect of reactive oxygen species on motility parameters, DNA integrity, tyrosine phosphorylation and phosphatase activity of common carp (Cyprinus carpio L.) spermatozoa. 25556750 7 6 theme dose-dependent 1109:1122 arg1 manner 1124:1129 a dose-dependent manner 1107:1129 a dose-dependent manner 1107:1129 Acid phosphatase activity also decreased in a dose-dependent manner after a 60 min exposure to oxidative stress. 25556750 1 7 from activity 285:292 arg1 spermatozoa 335:345 spermatozoa 335:345 spermatozoa of the common carp (Cyprinus carpio) 335:382 The effect of reactive oxygen species production on the motility parameters, DNA integrity, acid phosphatase activity, and protein tyrosine phosphorylation in spermatozoa of the common carp (Cyprinus carpio) was investigated. 25556750 1 8 theme motility 232:239 arg1 phosphorylation 316:330 protein tyrosine phosphorylation 299:330 protein tyrosine phosphorylation in spermatozoa of the common carp (Cyprinus carpio) 299:382 The effect of reactive oxygen species production on the motility parameters, DNA integrity, acid phosphatase activity, and protein tyrosine phosphorylation in spermatozoa of the common carp (Cyprinus carpio) was investigated. 25556750 1 8 theme motility 232:239 arg1 activity 285:292 acid phosphatase activity 268:292 acid phosphatase activity 268:292 The effect of reactive oxygen species production on the motility parameters, DNA integrity, acid phosphatase activity, and protein tyrosine phosphorylation in spermatozoa of the common carp (Cyprinus carpio) was investigated. 25556750 1 8 theme motility 232:239 arg1 parameters 241:250 the motility parameters 228:250 the motility parameters 228:250 The effect of reactive oxygen species production on the motility parameters, DNA integrity, acid phosphatase activity, and protein tyrosine phosphorylation in spermatozoa of the common carp (Cyprinus carpio) was investigated. 25556750 1 8 theme motility 232:239 arg1 integrity 257:265 DNA integrity 253:265 DNA integrity 253:265 The effect of reactive oxygen species production on the motility parameters, DNA integrity, acid phosphatase activity, and protein tyrosine phosphorylation in spermatozoa of the common carp (Cyprinus carpio) was investigated. 25556750 0 9 theme tyrosine 77:84 arg1 phosphorylation 86:100 tyrosine phosphorylation 77:100 tyrosine phosphorylation 77:100 The effect of reactive oxygen species on motility parameters, DNA integrity, tyrosine phosphorylation and phosphatase activity of common carp (Cyprinus carpio L.) spermatozoa. 25556750 0 9 theme tyrosine 77:84 arg1 effect 4:9 The effect 0:9 The effect of reactive oxygen species on motility parameters 0:59 The effect of reactive oxygen species on motility parameters, DNA integrity, tyrosine phosphorylation and phosphatase activity of common carp (Cyprinus carpio L.) spermatozoa. 25556750 2 10 theme xanthine 458:465 arg1 concentrations 440:453 different concentrations 430:453 different concentrations of xanthine and xanthine oxidase (X-XO) 430:493 Spermatozoa were exposed to different concentrations of xanthine and xanthine oxidase (X-XO) either in the presence or absence of antioxidants for 15 and 60 min. 25556750 8 11 theme tyrosine 1380:1387 arg1 phosphorylation 1389:1403 tyrosine phosphorylation 1380:1403 tyrosine phosphorylation 1380:1403 The results demonstrate that oxidative stress impaired functional variables (sperm motility, velocity, DNA integrity) of carp spermatozoa, and altered intracellular signalling pathways through changes in tyrosine phosphorylation and acid phosphatase activity. 25556750 0 12 theme spermatozoa 163:173 arg1 phosphorylation 86:100 tyrosine phosphorylation 77:100 tyrosine phosphorylation 77:100 The effect of reactive oxygen species on motility parameters, DNA integrity, tyrosine phosphorylation and phosphatase activity of common carp (Cyprinus carpio L.) spermatozoa. 25556750 0 12 theme spermatozoa 163:173 arg1 activity 118:125 phosphatase activity 106:125 phosphatase activity 106:125 The effect of reactive oxygen species on motility parameters, DNA integrity, tyrosine phosphorylation and phosphatase activity of common carp (Cyprinus carpio L.) spermatozoa. 25556750 0 12 theme spermatozoa 163:173 arg1 effect 4:9 The effect 0:9 The effect of reactive oxygen species on motility parameters 0:59 The effect of reactive oxygen species on motility parameters, DNA integrity, tyrosine phosphorylation and phosphatase activity of common carp (Cyprinus carpio L.) spermatozoa. 25556750 8 13 theme oxidative 1205:1213 arg1 stress 1215:1220 oxidative stress 1205:1220 oxidative stress 1205:1220 The results demonstrate that oxidative stress impaired functional variables (sperm motility, velocity, DNA integrity) of carp spermatozoa, and altered intracellular signalling pathways through changes in tyrosine phosphorylation and acid phosphatase activity. 25556750 1 14 from phosphorylation 316:330 arg1 spermatozoa 335:345 spermatozoa 335:345 spermatozoa of the common carp (Cyprinus carpio) 335:382 The effect of reactive oxygen species production on the motility parameters, DNA integrity, acid phosphatase activity, and protein tyrosine phosphorylation in spermatozoa of the common carp (Cyprinus carpio) was investigated. 25556750 8 15 from changes 1369:1375 arg1 phosphorylation 1389:1403 tyrosine phosphorylation 1380:1403 tyrosine phosphorylation 1380:1403 The results demonstrate that oxidative stress impaired functional variables (sperm motility, velocity, DNA integrity) of carp spermatozoa, and altered intracellular signalling pathways through changes in tyrosine phosphorylation and acid phosphatase activity. 25556750 8 15 from changes 1369:1375 arg1 activity 1426:1433 acid phosphatase activity 1409:1433 acid phosphatase activity 1409:1433 The results demonstrate that oxidative stress impaired functional variables (sperm motility, velocity, DNA integrity) of carp spermatozoa, and altered intracellular signalling pathways through changes in tyrosine phosphorylation and acid phosphatase activity. 25556750 8 16 theme intracellular 1327:1339 arg1 pathways 1352:1359 intracellular signalling pathways 1327:1359 intracellular signalling pathways 1327:1359 The results demonstrate that oxidative stress impaired functional variables (sperm motility, velocity, DNA integrity) of carp spermatozoa, and altered intracellular signalling pathways through changes in tyrosine phosphorylation and acid phosphatase activity. 25556750 1 17 theme common 354:359 arg1 carp 361:364 the common carp 350:364 the common carp (Cyprinus carpio) 350:382 The effect of reactive oxygen species production on the motility parameters, DNA integrity, acid phosphatase activity, and protein tyrosine phosphorylation in spermatozoa of the common carp (Cyprinus carpio) was investigated. 25556750 1 17 theme common 354:359 arg1 carpio 376:381 Cyprinus carpio 367:381 Cyprinus carpio 367:381 The effect of reactive oxygen species production on the motility parameters, DNA integrity, acid phosphatase activity, and protein tyrosine phosphorylation in spermatozoa of the common carp (Cyprinus carpio) was investigated. 25556750 7 18 theme phosphatase 1068:1078 arg1 activity 1080:1087 Acid phosphatase activity 1063:1087 Acid phosphatase activity 1063:1087 Acid phosphatase activity also decreased in a dose-dependent manner after a 60 min exposure to oxidative stress. 25556750 8 19 theme sperm 1253:1257 arg1 velocity 1269:1276 velocity 1269:1276 velocity 1269:1276 The results demonstrate that oxidative stress impaired functional variables (sperm motility, velocity, DNA integrity) of carp spermatozoa, and altered intracellular signalling pathways through changes in tyrosine phosphorylation and acid phosphatase activity. 25556750 8 19 theme sperm 1253:1257 arg1 integrity 1283:1291 DNA integrity 1279:1291 DNA integrity 1279:1291 The results demonstrate that oxidative stress impaired functional variables (sperm motility, velocity, DNA integrity) of carp spermatozoa, and altered intracellular signalling pathways through changes in tyrosine phosphorylation and acid phosphatase activity. 25556750 8 19 theme sperm 1253:1257 arg1 motility 1259:1266 sperm motility 1253:1266 sperm motility 1253:1266 The results demonstrate that oxidative stress impaired functional variables (sperm motility, velocity, DNA integrity) of carp spermatozoa, and altered intracellular signalling pathways through changes in tyrosine phosphorylation and acid phosphatase activity. 25556750 8 20 theme phosphatase 1414:1424 arg1 activity 1426:1433 acid phosphatase activity 1409:1433 acid phosphatase activity 1409:1433 The results demonstrate that oxidative stress impaired functional variables (sperm motility, velocity, DNA integrity) of carp spermatozoa, and altered intracellular signalling pathways through changes in tyrosine phosphorylation and acid phosphatase activity. 25556750 3 21 from reduction 591:599 arg1 motility 616:623 spermatozoa motility 604:623 spermatozoa motility 604:623 A dose- and time-dependent reduction in spermatozoa motility and velocity was observed. 25556750 3 21 from reduction 591:599 arg1 velocity 629:636 velocity 629:636 velocity 629:636 A dose- and time-dependent reduction in spermatozoa motility and velocity was observed. 25556750 1 22 theme DNA 253:255 arg1 parameters 241:250 the motility parameters 228:250 the motility parameters 228:250 The effect of reactive oxygen species production on the motility parameters, DNA integrity, acid phosphatase activity, and protein tyrosine phosphorylation in spermatozoa of the common carp (Cyprinus carpio) was investigated. 25556750 1 22 theme DNA 253:255 arg1 integrity 257:265 DNA integrity 253:265 DNA integrity 253:265 The effect of reactive oxygen species production on the motility parameters, DNA integrity, acid phosphatase activity, and protein tyrosine phosphorylation in spermatozoa of the common carp (Cyprinus carpio) was investigated. 25556750 1 23 from integrity 257:265 arg1 spermatozoa 335:345 spermatozoa 335:345 spermatozoa of the common carp (Cyprinus carpio) 335:382 The effect of reactive oxygen species production on the motility parameters, DNA integrity, acid phosphatase activity, and protein tyrosine phosphorylation in spermatozoa of the common carp (Cyprinus carpio) was investigated. 25556750 5 24 with blotting 812:819 arg1 antibodies 847:856 anti-phosphotyrosine antibodies 826:856 anti-phosphotyrosine antibodies 826:856 Changes in tyrosine phosphorylation of spermatozoa proteins were observed by Western blotting with anti-phosphotyrosine antibodies, and proteins of interest were identified by mass spectrometry. 25556750 5 25 theme interest 875:882 arg1 proteins 863:870 proteins 863:870 proteins of interest 863:882 Changes in tyrosine phosphorylation of spermatozoa proteins were observed by Western blotting with anti-phosphotyrosine antibodies, and proteins of interest were identified by mass spectrometry. 25556750 0 26 theme reactive 14:21 arg1 species 30:36 reactive oxygen species 14:36 reactive oxygen species 14:36 The effect of reactive oxygen species on motility parameters, DNA integrity, tyrosine phosphorylation and phosphatase activity of common carp (Cyprinus carpio L.) spermatozoa. 25556750 6 27 theme N-acetylglucosamine 964:982 arg1 isoform 997:1003 isoform 4 997:1005 isoform 4 997:1005 After a 60 min exposure to X-XO, O-linked N-acetylglucosamine transferase, isoform 4 was phosphorylated and septin-8-A was dephosphorylated. 25556750 6 27 theme N-acetylglucosamine 964:982 arg1 transferase 984:994 O-linked N-acetylglucosamine transferase 955:994 O-linked N-acetylglucosamine transferase 955:994 After a 60 min exposure to X-XO, O-linked N-acetylglucosamine transferase, isoform 4 was phosphorylated and septin-8-A was dephosphorylated. 25556750 7 28 theme 60 min 1139:1144 arg1 exposure 1146:1153 a 60 min exposure 1137:1153 a 60 min exposure to oxidative stress 1137:1173 Acid phosphatase activity also decreased in a dose-dependent manner after a 60 min exposure to oxidative stress. 25556750 5 29 theme proteins 778:785 arg1 phosphorylation 747:761 tyrosine phosphorylation 738:761 tyrosine phosphorylation of spermatozoa proteins 738:785 Changes in tyrosine phosphorylation of spermatozoa proteins were observed by Western blotting with anti-phosphotyrosine antibodies, and proteins of interest were identified by mass spectrometry. 25556750 5 30 theme tyrosine 738:745 arg1 phosphorylation 747:761 tyrosine phosphorylation 738:761 tyrosine phosphorylation of spermatozoa proteins 738:785 Changes in tyrosine phosphorylation of spermatozoa proteins were observed by Western blotting with anti-phosphotyrosine antibodies, and proteins of interest were identified by mass spectrometry. 25556750 8 31 theme acid 1409:1412 arg1 phosphatase 1414:1424 acid phosphatase 1409:1424 acid phosphatase activity 1409:1433 The results demonstrate that oxidative stress impaired functional variables (sperm motility, velocity, DNA integrity) of carp spermatozoa, and altered intracellular signalling pathways through changes in tyrosine phosphorylation and acid phosphatase activity. 25556750 6 32 theme O-linked 955:962 arg1 isoform 997:1003 isoform 4 997:1005 isoform 4 997:1005 After a 60 min exposure to X-XO, O-linked N-acetylglucosamine transferase, isoform 4 was phosphorylated and septin-8-A was dephosphorylated. 25556750 6 32 theme O-linked 955:962 arg1 transferase 984:994 O-linked N-acetylglucosamine transferase 955:994 O-linked N-acetylglucosamine transferase 955:994 After a 60 min exposure to X-XO, O-linked N-acetylglucosamine transferase, isoform 4 was phosphorylated and septin-8-A was dephosphorylated. 25556750 0 33 theme phosphatase 106:116 arg1 activity 118:125 phosphatase activity 106:125 phosphatase activity 106:125 The effect of reactive oxygen species on motility parameters, DNA integrity, tyrosine phosphorylation and phosphatase activity of common carp (Cyprinus carpio L.) spermatozoa. 25556750 0 33 theme phosphatase 106:116 arg1 effect 4:9 The effect 0:9 The effect of reactive oxygen species on motility parameters 0:59 The effect of reactive oxygen species on motility parameters, DNA integrity, tyrosine phosphorylation and phosphatase activity of common carp (Cyprinus carpio L.) spermatozoa. 25556750 1 34 theme carp 361:364 arg1 spermatozoa 335:345 spermatozoa 335:345 spermatozoa of the common carp (Cyprinus carpio) 335:382 The effect of reactive oxygen species production on the motility parameters, DNA integrity, acid phosphatase activity, and protein tyrosine phosphorylation in spermatozoa of the common carp (Cyprinus carpio) was investigated. 25556750 5 35 theme mass 903:906 arg1 spectrometry 908:919 mass spectrometry 903:919 mass spectrometry 903:919 Changes in tyrosine phosphorylation of spermatozoa proteins were observed by Western blotting with anti-phosphotyrosine antibodies, and proteins of interest were identified by mass spectrometry. 25556750 5 36 theme anti-phosphotyrosine 826:845 arg1 antibodies 847:856 anti-phosphotyrosine antibodies 826:856 anti-phosphotyrosine antibodies 826:856 Changes in tyrosine phosphorylation of spermatozoa proteins were observed by Western blotting with anti-phosphotyrosine antibodies, and proteins of interest were identified by mass spectrometry. 25556750 0 37 theme species 30:36 arg1 integrity 66:74 DNA integrity 62:74 DNA integrity 62:74 The effect of reactive oxygen species on motility parameters, DNA integrity, tyrosine phosphorylation and phosphatase activity of common carp (Cyprinus carpio L.) spermatozoa. 25556750 0 37 theme species 30:36 arg1 phosphorylation 86:100 tyrosine phosphorylation 77:100 tyrosine phosphorylation 77:100 The effect of reactive oxygen species on motility parameters, DNA integrity, tyrosine phosphorylation and phosphatase activity of common carp (Cyprinus carpio L.) spermatozoa. 25556750 0 37 theme species 30:36 arg1 effect 4:9 The effect 0:9 The effect of reactive oxygen species on motility parameters 0:59 The effect of reactive oxygen species on motility parameters, DNA integrity, tyrosine phosphorylation and phosphatase activity of common carp (Cyprinus carpio L.) spermatozoa. 25556750 0 37 theme species 30:36 arg1 activity 118:125 phosphatase activity 106:125 phosphatase activity 106:125 The effect of reactive oxygen species on motility parameters, DNA integrity, tyrosine phosphorylation and phosphatase activity of common carp (Cyprinus carpio L.) spermatozoa. 25556750 1 38 theme acid 268:271 arg1 phosphatase 273:283 acid phosphatase 268:283 acid phosphatase activity 268:292 The effect of reactive oxygen species production on the motility parameters, DNA integrity, acid phosphatase activity, and protein tyrosine phosphorylation in spermatozoa of the common carp (Cyprinus carpio) was investigated. 25556750 0 39 theme common 130:135 arg1 Cyprinus 143:150 Cyprinus 143:150 Cyprinus 143:150 The effect of reactive oxygen species on motility parameters, DNA integrity, tyrosine phosphorylation and phosphatase activity of common carp (Cyprinus carpio L.) spermatozoa. 25556750 0 39 theme common 130:135 arg1 carp 137:140 common carp 130:140 common carp (Cyprinus carpio L.) spermatozoa 130:173 The effect of reactive oxygen species on motility parameters, DNA integrity, tyrosine phosphorylation and phosphatase activity of common carp (Cyprinus carpio L.) spermatozoa. 25556750 8 40 theme spermatozoa 1302:1312 arg1 variables 1242:1250 functional variables 1231:1250 functional variables (sperm motility, velocity, DNA integrity) of carp spermatozoa 1231:1312 The results demonstrate that oxidative stress impaired functional variables (sperm motility, velocity, DNA integrity) of carp spermatozoa, and altered intracellular signalling pathways through changes in tyrosine phosphorylation and acid phosphatase activity. 25556750 6 41 link O-linked 955:962 arg1 isoform 997:1003 isoform 4 997:1005 isoform 4 997:1005 After a 60 min exposure to X-XO, O-linked N-acetylglucosamine transferase, isoform 4 was phosphorylated and septin-8-A was dephosphorylated. 25556750 6 41 link O-linked 955:962 arg1 transferase 984:994 O-linked N-acetylglucosamine transferase 955:994 O-linked N-acetylglucosamine transferase 955:994 After a 60 min exposure to X-XO, O-linked N-acetylglucosamine transferase, isoform 4 was phosphorylated and septin-8-A was dephosphorylated. 25556750 8 42 theme DNA 1279:1281 arg1 integrity 1283:1291 DNA integrity 1279:1291 DNA integrity 1279:1291 The results demonstrate that oxidative stress impaired functional variables (sperm motility, velocity, DNA integrity) of carp spermatozoa, and altered intracellular signalling pathways through changes in tyrosine phosphorylation and acid phosphatase activity. 25556750 8 42 theme DNA 1279:1281 arg1 motility 1259:1266 sperm motility 1253:1266 sperm motility 1253:1266 The results demonstrate that oxidative stress impaired functional variables (sperm motility, velocity, DNA integrity) of carp spermatozoa, and altered intracellular signalling pathways through changes in tyrosine phosphorylation and acid phosphatase activity. 25556750 7 43 theme oxidative 1158:1166 arg1 stress 1168:1173 oxidative stress 1158:1173 oxidative stress 1158:1173 Acid phosphatase activity also decreased in a dose-dependent manner after a 60 min exposure to oxidative stress. 25556750 0 44 theme oxygen 23:28 arg1 species 30:36 reactive oxygen species 14:36 reactive oxygen species 14:36 The effect of reactive oxygen species on motility parameters, DNA integrity, tyrosine phosphorylation and phosphatase activity of common carp (Cyprinus carpio L.) spermatozoa. 25556750 1 45 theme phosphatase 273:283 arg1 activity 285:292 acid phosphatase activity 268:292 acid phosphatase activity 268:292 The effect of reactive oxygen species production on the motility parameters, DNA integrity, acid phosphatase activity, and protein tyrosine phosphorylation in spermatozoa of the common carp (Cyprinus carpio) was investigated. 25556750 1 45 theme phosphatase 273:283 arg1 parameters 241:250 the motility parameters 228:250 the motility parameters 228:250 The effect of reactive oxygen species production on the motility parameters, DNA integrity, acid phosphatase activity, and protein tyrosine phosphorylation in spermatozoa of the common carp (Cyprinus carpio) was investigated. 25556750 5 46 theme spermatozoa 766:776 arg1 proteins 778:785 spermatozoa proteins 766:785 spermatozoa proteins 766:785 Changes in tyrosine phosphorylation of spermatozoa proteins were observed by Western blotting with anti-phosphotyrosine antibodies, and proteins of interest were identified by mass spectrometry. 25556750 1 47 theme Cyprinus 367:374 arg1 carp 361:364 the common carp 350:364 the common carp (Cyprinus carpio) 350:382 The effect of reactive oxygen species production on the motility parameters, DNA integrity, acid phosphatase activity, and protein tyrosine phosphorylation in spermatozoa of the common carp (Cyprinus carpio) was investigated. 25556750 1 47 theme Cyprinus 367:374 arg1 carpio 376:381 Cyprinus carpio 367:381 Cyprinus carpio 367:381 The effect of reactive oxygen species production on the motility parameters, DNA integrity, acid phosphatase activity, and protein tyrosine phosphorylation in spermatozoa of the common carp (Cyprinus carpio) was investigated. 25556750 5 48 theme Western 804:810 arg1 blotting 812:819 Western blotting 804:819 Western blotting with anti-phosphotyrosine antibodies 804:856 Changes in tyrosine phosphorylation of spermatozoa proteins were observed by Western blotting with anti-phosphotyrosine antibodies, and proteins of interest were identified by mass spectrometry. 25556750 1 49 theme reactive 190:197 arg1 species 206:212 reactive oxygen species 190:212 reactive oxygen species production 190:223 The effect of reactive oxygen species production on the motility parameters, DNA integrity, acid phosphatase activity, and protein tyrosine phosphorylation in spermatozoa of the common carp (Cyprinus carpio) was investigated. 25556750 0 50 theme motility 41:48 arg1 parameters 50:59 motility parameters 41:59 motility parameters 41:59 The effect of reactive oxygen species on motility parameters, DNA integrity, tyrosine phosphorylation and phosphatase activity of common carp (Cyprinus carpio L.) spermatozoa. 25556750 2 51 dep presence 509:516 arg1 the 505:507 the 505:507 the 505:507 Spermatozoa were exposed to different concentrations of xanthine and xanthine oxidase (X-XO) either in the presence or absence of antioxidants for 15 and 60 min. 25556750 7 52 theme Acid 1063:1066 arg1 activity 1080:1087 Acid phosphatase activity 1063:1087 Acid phosphatase activity 1063:1087 Acid phosphatase activity also decreased in a dose-dependent manner after a 60 min exposure to oxidative stress. 25556750 3 53 theme spermatozoa 604:614 arg1 motility 616:623 spermatozoa motility 604:623 spermatozoa motility 604:623 A dose- and time-dependent reduction in spermatozoa motility and velocity was observed. 25556750 2 54 theme different 430:438 arg1 concentrations 440:453 different concentrations 430:453 different concentrations of xanthine and xanthine oxidase (X-XO) 430:493 Spermatozoa were exposed to different concentrations of xanthine and xanthine oxidase (X-XO) either in the presence or absence of antioxidants for 15 and 60 min. 25556750 0 55 theme carp 137:140 arg1 spermatozoa 163:173 common carp (Cyprinus carpio L.) spermatozoa 130:173 common carp (Cyprinus carpio L.) spermatozoa 130:173 The effect of reactive oxygen species on motility parameters, DNA integrity, tyrosine phosphorylation and phosphatase activity of common carp (Cyprinus carpio L.) spermatozoa. 25556750 0 56 dep Cyprinus 143:150 arg1 L. 159:160 Cyprinus carpio L. 143:160 Cyprinus carpio L. 143:160 The effect of reactive oxygen species on motility parameters, DNA integrity, tyrosine phosphorylation and phosphatase activity of common carp (Cyprinus carpio L.) spermatozoa. 25556750 6 57 theme 60 min 930:935 arg1 exposure 937:944 a 60 min exposure 928:944 a 60 min exposure to X-XO 928:952 After a 60 min exposure to X-XO, O-linked N-acetylglucosamine transferase, isoform 4 was phosphorylated and septin-8-A was dephosphorylated. 25556750 2 58 theme antioxidants 532:543 arg1 absence 521:527 absence 521:527 absence 521:527 Spermatozoa were exposed to different concentrations of xanthine and xanthine oxidase (X-XO) either in the presence or absence of antioxidants for 15 and 60 min. 25556750 2 58 theme antioxidants 532:543 arg1 presence 509:516 presence 509:516 presence 509:516 Spermatozoa were exposed to different concentrations of xanthine and xanthine oxidase (X-XO) either in the presence or absence of antioxidants for 15 and 60 min. 25556750 3 59 theme time-dependent 576:589 arg1 reduction 591:599 A dose- and time-dependent reduction 564:599 A dose- and time-dependent reduction in spermatozoa motility and velocity 564:636 A dose- and time-dependent reduction in spermatozoa motility and velocity was observed. 25556750 1 60 from effect 180:185 arg1 phosphorylation 316:330 protein tyrosine phosphorylation 299:330 protein tyrosine phosphorylation in spermatozoa of the common carp (Cyprinus carpio) 299:382 The effect of reactive oxygen species production on the motility parameters, DNA integrity, acid phosphatase activity, and protein tyrosine phosphorylation in spermatozoa of the common carp (Cyprinus carpio) was investigated. 25556750 1 60 from effect 180:185 arg1 activity 285:292 acid phosphatase activity 268:292 acid phosphatase activity 268:292 The effect of reactive oxygen species production on the motility parameters, DNA integrity, acid phosphatase activity, and protein tyrosine phosphorylation in spermatozoa of the common carp (Cyprinus carpio) was investigated. 25556750 1 60 from effect 180:185 arg1 parameters 241:250 the motility parameters 228:250 the motility parameters 228:250 The effect of reactive oxygen species production on the motility parameters, DNA integrity, acid phosphatase activity, and protein tyrosine phosphorylation in spermatozoa of the common carp (Cyprinus carpio) was investigated. 25556750 1 60 from effect 180:185 arg1 integrity 257:265 DNA integrity 253:265 DNA integrity 253:265 The effect of reactive oxygen species production on the motility parameters, DNA integrity, acid phosphatase activity, and protein tyrosine phosphorylation in spermatozoa of the common carp (Cyprinus carpio) was investigated. 25556750 4 61 theme DNA 695:697 arg1 fragmentation 699:711 DNA fragmentation 695:711 DNA fragmentation after 15 min 695:724 Comet assays showed a dramatic increase in DNA fragmentation after 15 min. 25556750 1 62 theme oxygen 199:204 arg1 species 206:212 reactive oxygen species 190:212 reactive oxygen species production 190:223 The effect of reactive oxygen species production on the motility parameters, DNA integrity, acid phosphatase activity, and protein tyrosine phosphorylation in spermatozoa of the common carp (Cyprinus carpio) was investigated. 25556750 5 63 from Changes 727:733 arg1 phosphorylation 747:761 tyrosine phosphorylation 738:761 tyrosine phosphorylation of spermatozoa proteins 738:785 Changes in tyrosine phosphorylation of spermatozoa proteins were observed by Western blotting with anti-phosphotyrosine antibodies, and proteins of interest were identified by mass spectrometry. 25556750 8 64 theme signalling 1341:1350 arg1 pathways 1352:1359 intracellular signalling pathways 1327:1359 intracellular signalling pathways 1327:1359 The results demonstrate that oxidative stress impaired functional variables (sperm motility, velocity, DNA integrity) of carp spermatozoa, and altered intracellular signalling pathways through changes in tyrosine phosphorylation and acid phosphatase activity. 25556750 4 65 from increase 683:690 arg1 fragmentation 699:711 DNA fragmentation 695:711 DNA fragmentation after 15 min 695:724 Comet assays showed a dramatic increase in DNA fragmentation after 15 min. 25556750 1 66 theme species 206:212 arg1 production 214:223 reactive oxygen species production 190:223 reactive oxygen species production 190:223 The effect of reactive oxygen species production on the motility parameters, DNA integrity, acid phosphatase activity, and protein tyrosine phosphorylation in spermatozoa of the common carp (Cyprinus carpio) was investigated. 25556750 8 67 theme carp 1297:1300 arg1 spermatozoa 1302:1312 carp spermatozoa 1297:1312 carp spermatozoa 1297:1312 The results demonstrate that oxidative stress impaired functional variables (sperm motility, velocity, DNA integrity) of carp spermatozoa, and altered intracellular signalling pathways through changes in tyrosine phosphorylation and acid phosphatase activity. 25556750 3 68 theme dose- 566:570 arg1 reduction 591:599 A dose- and time-dependent reduction 564:599 A dose- and time-dependent reduction in spermatozoa motility and velocity 564:636 A dose- and time-dependent reduction in spermatozoa motility and velocity was observed. 25556750 1 69 theme production 214:223 arg1 effect 180:185 The effect 176:185 The effect of reactive oxygen species production on the motility parameters, DNA integrity, acid phosphatase activity, and protein tyrosine phosphorylation in spermatozoa of the common carp (Cyprinus carpio) 176:382 The effect of reactive oxygen species production on the motility parameters, DNA integrity, acid phosphatase activity, and protein tyrosine phosphorylation in spermatozoa of the common carp (Cyprinus carpio) was investigated. 25556750 2 70 theme oxidase 480:486 arg1 concentrations 440:453 different concentrations 430:453 different concentrations of xanthine and xanthine oxidase (X-XO) 430:493 Spermatozoa were exposed to different concentrations of xanthine and xanthine oxidase (X-XO) either in the presence or absence of antioxidants for 15 and 60 min. 25556750 1 71 theme protein 299:305 arg1 phosphorylation 316:330 protein tyrosine phosphorylation 299:330 protein tyrosine phosphorylation in spermatozoa of the common carp (Cyprinus carpio) 299:382 The effect of reactive oxygen species production on the motility parameters, DNA integrity, acid phosphatase activity, and protein tyrosine phosphorylation in spermatozoa of the common carp (Cyprinus carpio) was investigated. 25556750 1 71 theme protein 299:305 arg1 parameters 241:250 the motility parameters 228:250 the motility parameters 228:250 The effect of reactive oxygen species production on the motility parameters, DNA integrity, acid phosphatase activity, and protein tyrosine phosphorylation in spermatozoa of the common carp (Cyprinus carpio) was investigated. 25556750 8 72 theme functional 1231:1240 arg1 variables 1242:1250 functional variables 1231:1250 functional variables (sperm motility, velocity, DNA integrity) of carp spermatozoa 1231:1312 The results demonstrate that oxidative stress impaired functional variables (sperm motility, velocity, DNA integrity) of carp spermatozoa, and altered intracellular signalling pathways through changes in tyrosine phosphorylation and acid phosphatase activity. 25556750 4 73 theme Comet 652:656 arg1 assays 658:663 Comet assays 652:663 Comet assays 652:663 Comet assays showed a dramatic increase in DNA fragmentation after 15 min. 25556750 4 74 theme dramatic 674:681 arg1 increase 683:690 a dramatic increase 672:690 a dramatic increase in DNA fragmentation after 15 min 672:724 Comet assays showed a dramatic increase in DNA fragmentation after 15 min. 25515520 9 0 theme microscopy 1587:1596 arg1 analysis 1632:1639 Scanning electron microscopy (SEM) and fluorescence microscopy analysis 1569:1639 Scanning electron microscopy (SEM) and fluorescence microscopy analysis of the wild-type and AHA0618-mutant A. caviae strains 1569:1693 Scanning electron microscopy (SEM) and fluorescence microscopy analysis of the wild-type and AHA0618-mutant A. caviae strains revealed the mutant to be subtly but significantly shorter than wild-type cells; a phenomenon that could be recovered when either AHA0618 or H. pylori HP0518 were introduced. 25515520 7 1 from effects 1269:1275 arg1 status 1298:1303 the glycosylation status 1280:1303 the glycosylation status of the polar flagellins 1280:1327 Phenotypic analysis of an AHA0618 A. caviae mutant revealed increased swimming and swarming motility compared to the wild-type strain but without any detectable effects on the glycosylation status of the polar flagellins when analyzed by western blot analysis or mass spectroscopy. 25515520 9 2 dep cells 1769:1773 arg1 phenomenon 1778:1787 a phenomenon 1776:1787 wild-type cells; a phenomenon that could be recovered when either AHA0618 or H. pylori HP0518 were introduced 1759:1867 Scanning electron microscopy (SEM) and fluorescence microscopy analysis of the wild-type and AHA0618-mutant A. caviae strains revealed the mutant to be subtly but significantly shorter than wild-type cells; a phenomenon that could be recovered when either AHA0618 or H. pylori HP0518 were introduced. 25515520 6 3 from pylori 995:1000 arg1 HP0518 950:955 HP0518 950:955 HP0518 950:955 Here, we investigated the role of the AHA0618 gene, which shares homology (37% at the amino acid level) with the central region of a putative deglycosylation enzyme (HP0518) from the human pathogen Helicobacter pylori, which also glycosylates its flagellin and is proposed to be part of a flagellin deglycosylation pathway. 25515520 6 3 from pylori 995:1000 arg1 part 1063:1066 part 1063:1066 part of a flagellin deglycosylation pathway 1063:1105 Here, we investigated the role of the AHA0618 gene, which shares homology (37% at the amino acid level) with the central region of a putative deglycosylation enzyme (HP0518) from the human pathogen Helicobacter pylori, which also glycosylates its flagellin and is proposed to be part of a flagellin deglycosylation pathway. 25515520 6 3 from pylori 995:1000 arg1 enzyme 942:947 a putative deglycosylation enzyme 915:947 a putative deglycosylation enzyme (HP0518) 915:956 Here, we investigated the role of the AHA0618 gene, which shares homology (37% at the amino acid level) with the central region of a putative deglycosylation enzyme (HP0518) from the human pathogen Helicobacter pylori, which also glycosylates its flagellin and is proposed to be part of a flagellin deglycosylation pathway. 25515520 6 3 from pylori 995:1000 arg1 region 905:910 the central region 893:910 the central region of a putative deglycosylation enzyme (HP0518) from the human pathogen Helicobacter pylori, which also glycosylates its flagellin and is proposed to be part of a flagellin deglycosylation pathway 893:1105 Here, we investigated the role of the AHA0618 gene, which shares homology (37% at the amino acid level) with the central region of a putative deglycosylation enzyme (HP0518) from the human pathogen Helicobacter pylori, which also glycosylates its flagellin and is proposed to be part of a flagellin deglycosylation pathway. 25515520 9 4 theme H. 1836:1837 arg1 HP0518 1846:1851 H. pylori HP0518 1836:1851 H. pylori HP0518 1836:1851 Scanning electron microscopy (SEM) and fluorescence microscopy analysis of the wild-type and AHA0618-mutant A. caviae strains revealed the mutant to be subtly but significantly shorter than wild-type cells; a phenomenon that could be recovered when either AHA0618 or H. pylori HP0518 were introduced. 25515520 3 5 dep serine 464:469 arg1 residues 485:492 residues 485:492 residues 485:492 The two subunits of the polar flagellum, FlaA and FlaB, are posttranslationally modified by O-linked glycosylation with pseudaminic acid on 6-8 serine and threonine residues within the central region of these proteins. 25515520 5 6 theme simplest 637:644 arg1 genes 653:657 genes 653:657 genes required for bacterial glycosylation currently known 653:710 Aeromonas caviae possesses the simplest set of genes required for bacterial glycosylation currently known, with the putative glycosyltransferase, Maf1, being described recently. 25515520 5 6 theme simplest 637:644 arg1 set 646:648 the simplest set 633:648 the simplest set of genes required for bacterial glycosylation currently known 633:710 Aeromonas caviae possesses the simplest set of genes required for bacterial glycosylation currently known, with the putative glycosyltransferase, Maf1, being described recently. 25515520 6 7 theme deglycosylation 1083:1097 arg1 pathway 1099:1105 a flagellin deglycosylation pathway 1071:1105 a flagellin deglycosylation pathway 1071:1105 Here, we investigated the role of the AHA0618 gene, which shares homology (37% at the amino acid level) with the central region of a putative deglycosylation enzyme (HP0518) from the human pathogen Helicobacter pylori, which also glycosylates its flagellin and is proposed to be part of a flagellin deglycosylation pathway. 25515520 2 8 theme polar 243:247 arg1 flagellum 249:257 The polar flagellum 239:257 The polar flagellum 239:257 The polar flagellum also has a role in cellular adherence and biofilm formation. 25515520 9 9 theme microscopy 1621:1630 arg1 analysis 1632:1639 Scanning electron microscopy (SEM) and fluorescence microscopy analysis 1569:1639 Scanning electron microscopy (SEM) and fluorescence microscopy analysis of the wild-type and AHA0618-mutant A. caviae strains 1569:1693 Scanning electron microscopy (SEM) and fluorescence microscopy analysis of the wild-type and AHA0618-mutant A. caviae strains revealed the mutant to be subtly but significantly shorter than wild-type cells; a phenomenon that could be recovered when either AHA0618 or H. pylori HP0518 were introduced. 25515520 6 10 theme central 897:903 arg1 region 905:910 the central region 893:910 the central region of a putative deglycosylation enzyme (HP0518) from the human pathogen Helicobacter pylori, which also glycosylates its flagellin and is proposed to be part of a flagellin deglycosylation pathway 893:1105 Here, we investigated the role of the AHA0618 gene, which shares homology (37% at the amino acid level) with the central region of a putative deglycosylation enzyme (HP0518) from the human pathogen Helicobacter pylori, which also glycosylates its flagellin and is proposed to be part of a flagellin deglycosylation pathway. 25515520 4 11 theme flagellum 595:603 arg1 formation 578:586 the formation 574:586 the formation of the flagellum 574:603 This modification is essential for the formation of the flagellum. 25515520 5 12 theme bacterial 672:680 arg1 glycosylation 682:694 bacterial glycosylation 672:694 bacterial glycosylation 672:694 Aeromonas caviae possesses the simplest set of genes required for bacterial glycosylation currently known, with the putative glycosyltransferase, Maf1, being described recently. 25515520 1 13 theme lateral 178:184 arg1 system 195:200 a lateral flagella system 176:200 a lateral flagella system used for swarming on solid surfaces 176:236 Aeromonas caviae is motile via a polar flagellum in liquid culture, with a lateral flagella system used for swarming on solid surfaces. 25515520 9 14 theme wild-type 1648:1656 arg1 strains 1687:1693 the wild-type and AHA0618-mutant A. caviae strains 1644:1693 the wild-type and AHA0618-mutant A. caviae strains 1644:1693 Scanning electron microscopy (SEM) and fluorescence microscopy analysis of the wild-type and AHA0618-mutant A. caviae strains revealed the mutant to be subtly but significantly shorter than wild-type cells; a phenomenon that could be recovered when either AHA0618 or H. pylori HP0518 were introduced. 25515520 7 15 theme polar 1312:1316 arg1 flagellins 1318:1327 the polar flagellins 1308:1327 the polar flagellins 1308:1327 Phenotypic analysis of an AHA0618 A. caviae mutant revealed increased swimming and swarming motility compared to the wild-type strain but without any detectable effects on the glycosylation status of the polar flagellins when analyzed by western blot analysis or mass spectroscopy. 25515520 10 16 theme cell 2067:2070 arg1 wall 2072:2075 the bacterial cell wall 2053:2075 the bacterial cell wall 2053:2075 We can therefore conclude that AHA0618 does not affect A. caviae behavior by altering polar flagellin glycosylation levels but is likely to have a role in peptidoglycan processing at the bacterial cell wall, consequently altering cell length and hence influencing motility. 25515520 9 17 theme AHA0618-mutant 1662:1675 arg1 strains 1687:1693 the wild-type and AHA0618-mutant A. caviae strains 1644:1693 the wild-type and AHA0618-mutant A. caviae strains 1644:1693 Scanning electron microscopy (SEM) and fluorescence microscopy analysis of the wild-type and AHA0618-mutant A. caviae strains revealed the mutant to be subtly but significantly shorter than wild-type cells; a phenomenon that could be recovered when either AHA0618 or H. pylori HP0518 were introduced. 25515520 8 18 theme Bioinformatic 1390:1402 arg1 analysis 1404:1411 Bioinformatic analysis 1390:1411 Bioinformatic analysis 1390:1411 Bioinformatic analysis of the protein AHA0618, demonstrated homology to a family of l,d-transpeptidases involved in cell wall biology and peptidoglycan cross-linking (YkuD-like). 25515520 6 19 theme amino 870:874 arg1 level 881:885 the amino acid level 866:885 the amino acid level 866:885 Here, we investigated the role of the AHA0618 gene, which shares homology (37% at the amino acid level) with the central region of a putative deglycosylation enzyme (HP0518) from the human pathogen Helicobacter pylori, which also glycosylates its flagellin and is proposed to be part of a flagellin deglycosylation pathway. 25515520 9 20 theme caviae 1680:1685 arg1 strains 1687:1693 the wild-type and AHA0618-mutant A. caviae strains 1644:1693 the wild-type and AHA0618-mutant A. caviae strains 1644:1693 Scanning electron microscopy (SEM) and fluorescence microscopy analysis of the wild-type and AHA0618-mutant A. caviae strains revealed the mutant to be subtly but significantly shorter than wild-type cells; a phenomenon that could be recovered when either AHA0618 or H. pylori HP0518 were introduced. 25515520 7 21 theme glycosylation 1284:1296 arg1 status 1298:1303 the glycosylation status 1280:1303 the glycosylation status of the polar flagellins 1280:1327 Phenotypic analysis of an AHA0618 A. caviae mutant revealed increased swimming and swarming motility compared to the wild-type strain but without any detectable effects on the glycosylation status of the polar flagellins when analyzed by western blot analysis or mass spectroscopy. 25515520 10 22 theme polar 1956:1960 arg1 levels 1986:1991 polar flagellin glycosylation levels 1956:1991 polar flagellin glycosylation levels 1956:1991 We can therefore conclude that AHA0618 does not affect A. caviae behavior by altering polar flagellin glycosylation levels but is likely to have a role in peptidoglycan processing at the bacterial cell wall, consequently altering cell length and hence influencing motility. 25515520 8 23 theme protein 1420:1426 arg1 AHA0618 1428:1434 the protein AHA0618 1416:1434 the protein AHA0618 1416:1434 Bioinformatic analysis of the protein AHA0618, demonstrated homology to a family of l,d-transpeptidases involved in cell wall biology and peptidoglycan cross-linking (YkuD-like). 25515520 7 24 theme mutant 1152:1157 arg1 analysis 1119:1126 Phenotypic analysis 1108:1126 Phenotypic analysis of an AHA0618 A. caviae mutant 1108:1157 Phenotypic analysis of an AHA0618 A. caviae mutant revealed increased swimming and swarming motility compared to the wild-type strain but without any detectable effects on the glycosylation status of the polar flagellins when analyzed by western blot analysis or mass spectroscopy. 25515520 1 25 theme polar 136:140 arg1 flagellum 142:150 a polar flagellum 134:150 a polar flagellum in liquid culture 134:168 Aeromonas caviae is motile via a polar flagellum in liquid culture, with a lateral flagella system used for swarming on solid surfaces. 25515520 6 26 theme enzyme 942:947 arg1 region 905:910 the central region 893:910 the central region of a putative deglycosylation enzyme (HP0518) from the human pathogen Helicobacter pylori, which also glycosylates its flagellin and is proposed to be part of a flagellin deglycosylation pathway 893:1105 Here, we investigated the role of the AHA0618 gene, which shares homology (37% at the amino acid level) with the central region of a putative deglycosylation enzyme (HP0518) from the human pathogen Helicobacter pylori, which also glycosylates its flagellin and is proposed to be part of a flagellin deglycosylation pathway. 25515520 7 27 theme A. 1142:1143 arg1 mutant 1152:1157 an AHA0618 A. caviae mutant 1131:1157 an AHA0618 A. caviae mutant 1131:1157 Phenotypic analysis of an AHA0618 A. caviae mutant revealed increased swimming and swarming motility compared to the wild-type strain but without any detectable effects on the glycosylation status of the polar flagellins when analyzed by western blot analysis or mass spectroscopy. 25515520 1 28 from flagellum 142:150 arg1 culture 162:168 liquid culture 155:168 liquid culture 155:168 Aeromonas caviae is motile via a polar flagellum in liquid culture, with a lateral flagella system used for swarming on solid surfaces. 25515520 6 29 theme putative 917:924 arg1 HP0518 950:955 HP0518 950:955 HP0518 950:955 Here, we investigated the role of the AHA0618 gene, which shares homology (37% at the amino acid level) with the central region of a putative deglycosylation enzyme (HP0518) from the human pathogen Helicobacter pylori, which also glycosylates its flagellin and is proposed to be part of a flagellin deglycosylation pathway. 25515520 6 29 theme putative 917:924 arg1 part 1063:1066 part 1063:1066 part of a flagellin deglycosylation pathway 1063:1105 Here, we investigated the role of the AHA0618 gene, which shares homology (37% at the amino acid level) with the central region of a putative deglycosylation enzyme (HP0518) from the human pathogen Helicobacter pylori, which also glycosylates its flagellin and is proposed to be part of a flagellin deglycosylation pathway. 25515520 6 29 theme putative 917:924 arg1 enzyme 942:947 a putative deglycosylation enzyme 915:947 a putative deglycosylation enzyme (HP0518) 915:956 Here, we investigated the role of the AHA0618 gene, which shares homology (37% at the amino acid level) with the central region of a putative deglycosylation enzyme (HP0518) from the human pathogen Helicobacter pylori, which also glycosylates its flagellin and is proposed to be part of a flagellin deglycosylation pathway. 25515520 10 30 dep A. 1925:1926 arg1 caviae 1928:1933 caviae 1928:1933 caviae 1928:1933 We can therefore conclude that AHA0618 does not affect A. caviae behavior by altering polar flagellin glycosylation levels but is likely to have a role in peptidoglycan processing at the bacterial cell wall, consequently altering cell length and hence influencing motility. 25515520 10 31 theme glycosylation 1972:1984 arg1 levels 1986:1991 polar flagellin glycosylation levels 1956:1991 polar flagellin glycosylation levels 1956:1991 We can therefore conclude that AHA0618 does not affect A. caviae behavior by altering polar flagellin glycosylation levels but is likely to have a role in peptidoglycan processing at the bacterial cell wall, consequently altering cell length and hence influencing motility. 25515520 0 32 theme swarming 84:91 arg1 motility 93:100 swarming motility 84:100 swarming motility 84:100 The Aeromonas caviae AHA0618 gene modulates cell length and influences swimming and swarming motility. 25515520 7 33 theme mass 1371:1374 arg1 spectroscopy 1376:1387 mass spectroscopy 1371:1387 mass spectroscopy 1371:1387 Phenotypic analysis of an AHA0618 A. caviae mutant revealed increased swimming and swarming motility compared to the wild-type strain but without any detectable effects on the glycosylation status of the polar flagellins when analyzed by western blot analysis or mass spectroscopy. 25515520 3 34 theme polar 344:348 arg1 flagellum 350:358 the polar flagellum 340:358 the polar flagellum 340:358 The two subunits of the polar flagellum, FlaA and FlaB, are posttranslationally modified by O-linked glycosylation with pseudaminic acid on 6-8 serine and threonine residues within the central region of these proteins. 25515520 6 35 theme Helicobacter 982:993 arg1 pylori 995:1000 the human pathogen Helicobacter pylori 963:1000 the human pathogen Helicobacter pylori 963:1000 Here, we investigated the role of the AHA0618 gene, which shares homology (37% at the amino acid level) with the central region of a putative deglycosylation enzyme (HP0518) from the human pathogen Helicobacter pylori, which also glycosylates its flagellin and is proposed to be part of a flagellin deglycosylation pathway. 25515520 9 36 theme wild-type 1759:1767 arg1 cells 1769:1773 wild-type cells 1759:1773 wild-type cells; a phenomenon that could be recovered when either AHA0618 or H. pylori HP0518 were introduced 1759:1867 Scanning electron microscopy (SEM) and fluorescence microscopy analysis of the wild-type and AHA0618-mutant A. caviae strains revealed the mutant to be subtly but significantly shorter than wild-type cells; a phenomenon that could be recovered when either AHA0618 or H. pylori HP0518 were introduced. 25515520 7 37 theme blot 1354:1357 arg1 analysis 1359:1366 western blot analysis 1346:1366 western blot analysis 1346:1366 Phenotypic analysis of an AHA0618 A. caviae mutant revealed increased swimming and swarming motility compared to the wild-type strain but without any detectable effects on the glycosylation status of the polar flagellins when analyzed by western blot analysis or mass spectroscopy. 25515520 6 38 theme human 967:971 arg1 pylori 995:1000 the human pathogen Helicobacter pylori 963:1000 the human pathogen Helicobacter pylori 963:1000 Here, we investigated the role of the AHA0618 gene, which shares homology (37% at the amino acid level) with the central region of a putative deglycosylation enzyme (HP0518) from the human pathogen Helicobacter pylori, which also glycosylates its flagellin and is proposed to be part of a flagellin deglycosylation pathway. 25515520 6 39 from region 905:910 arg1 pylori 995:1000 the human pathogen Helicobacter pylori 963:1000 the human pathogen Helicobacter pylori 963:1000 Here, we investigated the role of the AHA0618 gene, which shares homology (37% at the amino acid level) with the central region of a putative deglycosylation enzyme (HP0518) from the human pathogen Helicobacter pylori, which also glycosylates its flagellin and is proposed to be part of a flagellin deglycosylation pathway. 25515520 6 40 theme AHA0618 822:828 arg1 gene 830:833 the AHA0618 gene 818:833 the AHA0618 gene 818:833 Here, we investigated the role of the AHA0618 gene, which shares homology (37% at the amino acid level) with the central region of a putative deglycosylation enzyme (HP0518) from the human pathogen Helicobacter pylori, which also glycosylates its flagellin and is proposed to be part of a flagellin deglycosylation pathway. 25515520 7 41 theme wild-type 1225:1233 arg1 strain 1235:1240 the wild-type strain 1221:1240 the wild-type strain 1221:1240 Phenotypic analysis of an AHA0618 A. caviae mutant revealed increased swimming and swarming motility compared to the wild-type strain but without any detectable effects on the glycosylation status of the polar flagellins when analyzed by western blot analysis or mass spectroscopy. 25515520 8 42 theme cell 1506:1509 arg1 biology 1516:1522 cell wall biology 1506:1522 cell wall biology 1506:1522 Bioinformatic analysis of the protein AHA0618, demonstrated homology to a family of l,d-transpeptidases involved in cell wall biology and peptidoglycan cross-linking (YkuD-like). 25515520 10 43 contain have 2010:2013 arg1 AHA0618 1901:1907 AHA0618 1901:1907 AHA0618 1901:1907 We can therefore conclude that AHA0618 does not affect A. caviae behavior by altering polar flagellin glycosylation levels but is likely to have a role in peptidoglycan processing at the bacterial cell wall, consequently altering cell length and hence influencing motility. 25515520 10 43 contain have 2010:2013 arg2 role 2017:2020 a role 2015:2020 a role 2015:2020 We can therefore conclude that AHA0618 does not affect A. caviae behavior by altering polar flagellin glycosylation levels but is likely to have a role in peptidoglycan processing at the bacterial cell wall, consequently altering cell length and hence influencing motility. 25515520 0 44 theme cell 44:47 arg1 length 49:54 cell length 44:54 cell length 44:54 The Aeromonas caviae AHA0618 gene modulates cell length and influences swimming and swarming motility. 25515520 10 45 from wall 2072:2075 arg1 processing 2039:2048 peptidoglycan processing 2025:2048 peptidoglycan processing at the bacterial cell wall 2025:2075 We can therefore conclude that AHA0618 does not affect A. caviae behavior by altering polar flagellin glycosylation levels but is likely to have a role in peptidoglycan processing at the bacterial cell wall, consequently altering cell length and hence influencing motility. 25515520 3 46 theme pseudaminic 440:450 arg1 acid 452:455 pseudaminic acid 440:455 pseudaminic acid 440:455 The two subunits of the polar flagellum, FlaA and FlaB, are posttranslationally modified by O-linked glycosylation with pseudaminic acid on 6-8 serine and threonine residues within the central region of these proteins. 25515520 8 47 theme peptidoglycan 1528:1540 arg1 YkuD-like 1557:1565 YkuD-like 1557:1565 YkuD-like 1557:1565 Bioinformatic analysis of the protein AHA0618, demonstrated homology to a family of l,d-transpeptidases involved in cell wall biology and peptidoglycan cross-linking (YkuD-like). 25515520 8 47 theme peptidoglycan 1528:1540 arg1 cross-linking 1542:1554 peptidoglycan cross-linking 1528:1554 peptidoglycan cross-linking (YkuD-like) 1528:1566 Bioinformatic analysis of the protein AHA0618, demonstrated homology to a family of l,d-transpeptidases involved in cell wall biology and peptidoglycan cross-linking (YkuD-like). 25515520 9 48 theme electron 1578:1585 arg1 SEM 1599:1601 SEM 1599:1601 SEM 1599:1601 Scanning electron microscopy (SEM) and fluorescence microscopy analysis of the wild-type and AHA0618-mutant A. caviae strains revealed the mutant to be subtly but significantly shorter than wild-type cells; a phenomenon that could be recovered when either AHA0618 or H. pylori HP0518 were introduced. 25515520 9 48 theme electron 1578:1585 arg1 microscopy 1587:1596 Scanning electron microscopy 1569:1596 Scanning electron microscopy (SEM) 1569:1602 Scanning electron microscopy (SEM) and fluorescence microscopy analysis of the wild-type and AHA0618-mutant A. caviae strains revealed the mutant to be subtly but significantly shorter than wild-type cells; a phenomenon that could be recovered when either AHA0618 or H. pylori HP0518 were introduced. 25515520 10 49 theme peptidoglycan 2025:2037 arg1 processing 2039:2048 peptidoglycan processing 2025:2048 peptidoglycan processing at the bacterial cell wall 2025:2075 We can therefore conclude that AHA0618 does not affect A. caviae behavior by altering polar flagellin glycosylation levels but is likely to have a role in peptidoglycan processing at the bacterial cell wall, consequently altering cell length and hence influencing motility. 25515520 6 50 dep homology 849:856 arg1 % 861:861 37% 859:861 37% 859:861 Here, we investigated the role of the AHA0618 gene, which shares homology (37% at the amino acid level) with the central region of a putative deglycosylation enzyme (HP0518) from the human pathogen Helicobacter pylori, which also glycosylates its flagellin and is proposed to be part of a flagellin deglycosylation pathway. 25515520 1 51 theme solid 223:227 arg1 surfaces 229:236 solid surfaces 223:236 solid surfaces 223:236 Aeromonas caviae is motile via a polar flagellum in liquid culture, with a lateral flagella system used for swarming on solid surfaces. 25515520 3 52 link O-linked 412:419 arg1 glycosylation 421:433 O-linked glycosylation 412:433 O-linked glycosylation with pseudaminic acid on 6-8 serine and threonine residues within the central region of these proteins 412:536 The two subunits of the polar flagellum, FlaA and FlaB, are posttranslationally modified by O-linked glycosylation with pseudaminic acid on 6-8 serine and threonine residues within the central region of these proteins. 25515520 7 53 theme increased 1168:1176 arg1 swimming 1178:1185 increased swimming 1168:1185 increased swimming 1168:1185 Phenotypic analysis of an AHA0618 A. caviae mutant revealed increased swimming and swarming motility compared to the wild-type strain but without any detectable effects on the glycosylation status of the polar flagellins when analyzed by western blot analysis or mass spectroscopy. 25515520 3 54 theme central 505:511 arg1 region 513:518 the central region 501:518 the central region of these proteins 501:536 The two subunits of the polar flagellum, FlaA and FlaB, are posttranslationally modified by O-linked glycosylation with pseudaminic acid on 6-8 serine and threonine residues within the central region of these proteins. 25515520 3 55 theme proteins 529:536 arg1 region 513:518 the central region 501:518 the central region of these proteins 501:536 The two subunits of the polar flagellum, FlaA and FlaB, are posttranslationally modified by O-linked glycosylation with pseudaminic acid on 6-8 serine and threonine residues within the central region of these proteins. 25515520 6 56 theme pathway 1099:1105 arg1 part 1063:1066 part 1063:1066 part of a flagellin deglycosylation pathway 1063:1105 Here, we investigated the role of the AHA0618 gene, which shares homology (37% at the amino acid level) with the central region of a putative deglycosylation enzyme (HP0518) from the human pathogen Helicobacter pylori, which also glycosylates its flagellin and is proposed to be part of a flagellin deglycosylation pathway. 25515520 6 56 theme pathway 1099:1105 arg1 enzyme 942:947 a putative deglycosylation enzyme 915:947 a putative deglycosylation enzyme (HP0518) 915:956 Here, we investigated the role of the AHA0618 gene, which shares homology (37% at the amino acid level) with the central region of a putative deglycosylation enzyme (HP0518) from the human pathogen Helicobacter pylori, which also glycosylates its flagellin and is proposed to be part of a flagellin deglycosylation pathway. 25515520 10 57 theme bacterial 2057:2065 arg1 wall 2072:2075 the bacterial cell wall 2053:2075 the bacterial cell wall 2053:2075 We can therefore conclude that AHA0618 does not affect A. caviae behavior by altering polar flagellin glycosylation levels but is likely to have a role in peptidoglycan processing at the bacterial cell wall, consequently altering cell length and hence influencing motility. 25515520 1 58 theme liquid 155:160 arg1 culture 162:168 liquid culture 155:168 liquid culture 155:168 Aeromonas caviae is motile via a polar flagellum in liquid culture, with a lateral flagella system used for swarming on solid surfaces. 25515520 9 59 theme fluorescence 1608:1619 arg1 microscopy 1621:1630 fluorescence microscopy 1608:1630 fluorescence microscopy 1608:1630 Scanning electron microscopy (SEM) and fluorescence microscopy analysis of the wild-type and AHA0618-mutant A. caviae strains revealed the mutant to be subtly but significantly shorter than wild-type cells; a phenomenon that could be recovered when either AHA0618 or H. pylori HP0518 were introduced. 25515520 6 60 theme flagellin 1073:1081 arg1 pathway 1099:1105 a flagellin deglycosylation pathway 1071:1105 a flagellin deglycosylation pathway 1071:1105 Here, we investigated the role of the AHA0618 gene, which shares homology (37% at the amino acid level) with the central region of a putative deglycosylation enzyme (HP0518) from the human pathogen Helicobacter pylori, which also glycosylates its flagellin and is proposed to be part of a flagellin deglycosylation pathway. 25515520 2 61 theme cellular 278:285 arg1 adherence 287:295 cellular adherence 278:295 cellular adherence 278:295 The polar flagellum also has a role in cellular adherence and biofilm formation. 25515520 7 62 gly glycosylation 1284:1296 arg1 flagellins 1318:1327 the polar flagellins 1308:1327 the polar flagellins 1308:1327 Phenotypic analysis of an AHA0618 A. caviae mutant revealed increased swimming and swarming motility compared to the wild-type strain but without any detectable effects on the glycosylation status of the polar flagellins when analyzed by western blot analysis or mass spectroscopy. 25515520 10 63 dep have 2010:2013 arg1 influencing 2122:2132 influencing 2122:2132 hence influencing motility 2116:2141 We can therefore conclude that AHA0618 does not affect A. caviae behavior by altering polar flagellin glycosylation levels but is likely to have a role in peptidoglycan processing at the bacterial cell wall, consequently altering cell length and hence influencing motility. 25515520 10 63 dep have 2010:2013 arg1 altering 2091:2098 altering 2091:2098 altering cell length 2091:2110 We can therefore conclude that AHA0618 does not affect A. caviae behavior by altering polar flagellin glycosylation levels but is likely to have a role in peptidoglycan processing at the bacterial cell wall, consequently altering cell length and hence influencing motility. 25515520 7 64 theme western 1346:1352 arg1 analysis 1359:1366 western blot analysis 1346:1366 western blot analysis 1346:1366 Phenotypic analysis of an AHA0618 A. caviae mutant revealed increased swimming and swarming motility compared to the wild-type strain but without any detectable effects on the glycosylation status of the polar flagellins when analyzed by western blot analysis or mass spectroscopy. 25515520 3 65 with glycosylation 421:433 arg1 acid 452:455 pseudaminic acid 440:455 pseudaminic acid 440:455 The two subunits of the polar flagellum, FlaA and FlaB, are posttranslationally modified by O-linked glycosylation with pseudaminic acid on 6-8 serine and threonine residues within the central region of these proteins. 25515520 1 66 theme flagella 186:193 arg1 system 195:200 a lateral flagella system 176:200 a lateral flagella system used for swarming on solid surfaces 176:236 Aeromonas caviae is motile via a polar flagellum in liquid culture, with a lateral flagella system used for swarming on solid surfaces. 25515520 7 67 theme flagellins 1318:1327 arg1 status 1298:1303 the glycosylation status 1280:1303 the glycosylation status of the polar flagellins 1280:1327 Phenotypic analysis of an AHA0618 A. caviae mutant revealed increased swimming and swarming motility compared to the wild-type strain but without any detectable effects on the glycosylation status of the polar flagellins when analyzed by western blot analysis or mass spectroscopy. 25515520 10 68 theme A. 1925:1926 arg1 behavior 1935:1942 A. caviae behavior 1925:1942 A. caviae behavior 1925:1942 We can therefore conclude that AHA0618 does not affect A. caviae behavior by altering polar flagellin glycosylation levels but is likely to have a role in peptidoglycan processing at the bacterial cell wall, consequently altering cell length and hence influencing motility. 25515520 1 69 from swarming 211:218 arg1 surfaces 229:236 solid surfaces 223:236 solid surfaces 223:236 Aeromonas caviae is motile via a polar flagellum in liquid culture, with a lateral flagella system used for swarming on solid surfaces. 25515520 6 70 theme acid 876:879 arg1 level 881:885 the amino acid level 866:885 the amino acid level 866:885 Here, we investigated the role of the AHA0618 gene, which shares homology (37% at the amino acid level) with the central region of a putative deglycosylation enzyme (HP0518) from the human pathogen Helicobacter pylori, which also glycosylates its flagellin and is proposed to be part of a flagellin deglycosylation pathway. 25515520 9 71 theme A. 1677:1678 arg1 strains 1687:1693 the wild-type and AHA0618-mutant A. caviae strains 1644:1693 the wild-type and AHA0618-mutant A. caviae strains 1644:1693 Scanning electron microscopy (SEM) and fluorescence microscopy analysis of the wild-type and AHA0618-mutant A. caviae strains revealed the mutant to be subtly but significantly shorter than wild-type cells; a phenomenon that could be recovered when either AHA0618 or H. pylori HP0518 were introduced. 25515520 10 72 theme cell 2100:2103 arg1 length 2105:2110 cell length 2100:2110 cell length 2100:2110 We can therefore conclude that AHA0618 does not affect A. caviae behavior by altering polar flagellin glycosylation levels but is likely to have a role in peptidoglycan processing at the bacterial cell wall, consequently altering cell length and hence influencing motility. 25515520 5 73 theme genes 653:657 arg1 genes 653:657 genes 653:657 genes required for bacterial glycosylation currently known 653:710 Aeromonas caviae possesses the simplest set of genes required for bacterial glycosylation currently known, with the putative glycosyltransferase, Maf1, being described recently. 25515520 5 73 theme genes 653:657 arg1 set 646:648 the simplest set 633:648 the simplest set of genes required for bacterial glycosylation currently known 633:710 Aeromonas caviae possesses the simplest set of genes required for bacterial glycosylation currently known, with the putative glycosyltransferase, Maf1, being described recently. 25515520 9 74 theme strains 1687:1693 arg1 analysis 1632:1639 Scanning electron microscopy (SEM) and fluorescence microscopy analysis 1569:1639 Scanning electron microscopy (SEM) and fluorescence microscopy analysis of the wild-type and AHA0618-mutant A. caviae strains 1569:1693 Scanning electron microscopy (SEM) and fluorescence microscopy analysis of the wild-type and AHA0618-mutant A. caviae strains revealed the mutant to be subtly but significantly shorter than wild-type cells; a phenomenon that could be recovered when either AHA0618 or H. pylori HP0518 were introduced. 25515520 8 75 theme AHA0618 1428:1434 arg1 analysis 1404:1411 Bioinformatic analysis 1390:1411 Bioinformatic analysis 1390:1411 Bioinformatic analysis of the protein AHA0618, demonstrated homology to a family of l,d-transpeptidases involved in cell wall biology and peptidoglycan cross-linking (YkuD-like). 25515520 5 76 theme putative 722:729 arg1 glycosyltransferase 731:749 the putative glycosyltransferase 718:749 the putative glycosyltransferase 718:749 Aeromonas caviae possesses the simplest set of genes required for bacterial glycosylation currently known, with the putative glycosyltransferase, Maf1, being described recently. 25515520 5 76 theme putative 722:729 arg1 Maf1 752:755 Maf1 752:755 Maf1 752:755 Aeromonas caviae possesses the simplest set of genes required for bacterial glycosylation currently known, with the putative glycosyltransferase, Maf1, being described recently. 25515520 7 77 theme AHA0618 1134:1140 arg1 mutant 1152:1157 an AHA0618 A. caviae mutant 1131:1157 an AHA0618 A. caviae mutant 1131:1157 Phenotypic analysis of an AHA0618 A. caviae mutant revealed increased swimming and swarming motility compared to the wild-type strain but without any detectable effects on the glycosylation status of the polar flagellins when analyzed by western blot analysis or mass spectroscopy. 25515520 3 78 mod modified 400:407 arg1 FlaA 361:364 FlaA 361:364 FlaA 361:364 The two subunits of the polar flagellum, FlaA and FlaB, are posttranslationally modified by O-linked glycosylation with pseudaminic acid on 6-8 serine and threonine residues within the central region of these proteins. 25515520 3 78 mod modified 400:407 arg1 FlaB 370:373 FlaB 370:373 FlaB 370:373 The two subunits of the polar flagellum, FlaA and FlaB, are posttranslationally modified by O-linked glycosylation with pseudaminic acid on 6-8 serine and threonine residues within the central region of these proteins. 25515520 3 78 mod modified 400:407 arg3 glycosylation 421:433 O-linked glycosylation 412:433 O-linked glycosylation with pseudaminic acid on 6-8 serine and threonine residues within the central region of these proteins 412:536 The two subunits of the polar flagellum, FlaA and FlaB, are posttranslationally modified by O-linked glycosylation with pseudaminic acid on 6-8 serine and threonine residues within the central region of these proteins. 25515520 3 78 mod modified 400:407 arg1 subunits 328:335 The two subunits 320:335 The two subunits of the polar flagellum 320:358 The two subunits of the polar flagellum, FlaA and FlaB, are posttranslationally modified by O-linked glycosylation with pseudaminic acid on 6-8 serine and threonine residues within the central region of these proteins. 25515520 6 79 theme deglycosylation 926:940 arg1 HP0518 950:955 HP0518 950:955 HP0518 950:955 Here, we investigated the role of the AHA0618 gene, which shares homology (37% at the amino acid level) with the central region of a putative deglycosylation enzyme (HP0518) from the human pathogen Helicobacter pylori, which also glycosylates its flagellin and is proposed to be part of a flagellin deglycosylation pathway. 25515520 6 79 theme deglycosylation 926:940 arg1 part 1063:1066 part 1063:1066 part of a flagellin deglycosylation pathway 1063:1105 Here, we investigated the role of the AHA0618 gene, which shares homology (37% at the amino acid level) with the central region of a putative deglycosylation enzyme (HP0518) from the human pathogen Helicobacter pylori, which also glycosylates its flagellin and is proposed to be part of a flagellin deglycosylation pathway. 25515520 6 79 theme deglycosylation 926:940 arg1 enzyme 942:947 a putative deglycosylation enzyme 915:947 a putative deglycosylation enzyme (HP0518) 915:956 Here, we investigated the role of the AHA0618 gene, which shares homology (37% at the amino acid level) with the central region of a putative deglycosylation enzyme (HP0518) from the human pathogen Helicobacter pylori, which also glycosylates its flagellin and is proposed to be part of a flagellin deglycosylation pathway. 25515520 5 80 theme known 706:710 arg1 genes 653:657 genes 653:657 genes required for bacterial glycosylation currently known 653:710 Aeromonas caviae possesses the simplest set of genes required for bacterial glycosylation currently known, with the putative glycosyltransferase, Maf1, being described recently. 25515520 6 81 gly glycosylates 1014:1025 arg1 flagellin 1031:1039 its flagellin 1027:1039 its flagellin 1027:1039 Here, we investigated the role of the AHA0618 gene, which shares homology (37% at the amino acid level) with the central region of a putative deglycosylation enzyme (HP0518) from the human pathogen Helicobacter pylori, which also glycosylates its flagellin and is proposed to be part of a flagellin deglycosylation pathway. 25515520 10 82 theme flagellin 1962:1970 arg1 levels 1986:1991 polar flagellin glycosylation levels 1956:1991 polar flagellin glycosylation levels 1956:1991 We can therefore conclude that AHA0618 does not affect A. caviae behavior by altering polar flagellin glycosylation levels but is likely to have a role in peptidoglycan processing at the bacterial cell wall, consequently altering cell length and hence influencing motility. 25515520 7 83 theme Phenotypic 1108:1117 arg1 analysis 1119:1126 Phenotypic analysis 1108:1126 Phenotypic analysis of an AHA0618 A. caviae mutant 1108:1157 Phenotypic analysis of an AHA0618 A. caviae mutant revealed increased swimming and swarming motility compared to the wild-type strain but without any detectable effects on the glycosylation status of the polar flagellins when analyzed by western blot analysis or mass spectroscopy. 25515520 1 84 with motile 123:128 arg1 system 195:200 a lateral flagella system 176:200 a lateral flagella system used for swarming on solid surfaces 176:236 Aeromonas caviae is motile via a polar flagellum in liquid culture, with a lateral flagella system used for swarming on solid surfaces. 25515520 7 85 theme detectable 1258:1267 arg1 effects 1269:1275 any detectable effects 1254:1275 any detectable effects on the glycosylation status of the polar flagellins 1254:1327 Phenotypic analysis of an AHA0618 A. caviae mutant revealed increased swimming and swarming motility compared to the wild-type strain but without any detectable effects on the glycosylation status of the polar flagellins when analyzed by western blot analysis or mass spectroscopy. 25515520 8 86 theme l 1474:1474 arg1 family 1464:1469 a family 1462:1469 a family of l,d-transpeptidases involved in cell wall biology and peptidoglycan cross-linking (YkuD-like) 1462:1566 Bioinformatic analysis of the protein AHA0618, demonstrated homology to a family of l,d-transpeptidases involved in cell wall biology and peptidoglycan cross-linking (YkuD-like). 25515520 0 87 theme Aeromonas 4:12 arg1 gene 29:32 The Aeromonas caviae AHA0618 gene 0:32 The Aeromonas caviae AHA0618 gene 0:32 The Aeromonas caviae AHA0618 gene modulates cell length and influences swimming and swarming motility. 25515520 9 88 dep H. 1836:1837 arg1 pylori 1839:1844 H. pylori 1836:1844 H. pylori HP0518 1836:1851 Scanning electron microscopy (SEM) and fluorescence microscopy analysis of the wild-type and AHA0618-mutant A. caviae strains revealed the mutant to be subtly but significantly shorter than wild-type cells; a phenomenon that could be recovered when either AHA0618 or H. pylori HP0518 were introduced. 25515520 7 89 dep revealed 1159:1166 arg1 compared 1209:1216 compared 1209:1216 revealed increased swimming and swarming motility compared to the wild-type strain but without any detectable effects on the glycosylation status of the polar flagellins when analyzed by western blot analysis or mass spectroscopy 1159:1387 Phenotypic analysis of an AHA0618 A. caviae mutant revealed increased swimming and swarming motility compared to the wild-type strain but without any detectable effects on the glycosylation status of the polar flagellins when analyzed by western blot analysis or mass spectroscopy. 25515520 3 90 theme flagellum 350:358 arg1 FlaA 361:364 FlaA 361:364 FlaA 361:364 The two subunits of the polar flagellum, FlaA and FlaB, are posttranslationally modified by O-linked glycosylation with pseudaminic acid on 6-8 serine and threonine residues within the central region of these proteins. 25515520 3 90 theme flagellum 350:358 arg1 FlaB 370:373 FlaB 370:373 FlaB 370:373 The two subunits of the polar flagellum, FlaA and FlaB, are posttranslationally modified by O-linked glycosylation with pseudaminic acid on 6-8 serine and threonine residues within the central region of these proteins. 25515520 3 90 theme flagellum 350:358 arg1 subunits 328:335 The two subunits 320:335 The two subunits of the polar flagellum 320:358 The two subunits of the polar flagellum, FlaA and FlaB, are posttranslationally modified by O-linked glycosylation with pseudaminic acid on 6-8 serine and threonine residues within the central region of these proteins. 25515520 8 91 theme d-transpeptidases 1476:1492 arg1 family 1464:1469 a family 1462:1469 a family of l,d-transpeptidases involved in cell wall biology and peptidoglycan cross-linking (YkuD-like) 1462:1566 Bioinformatic analysis of the protein AHA0618, demonstrated homology to a family of l,d-transpeptidases involved in cell wall biology and peptidoglycan cross-linking (YkuD-like). 25515520 0 92 theme AHA0618 21:27 arg1 gene 29:32 The Aeromonas caviae AHA0618 gene 0:32 The Aeromonas caviae AHA0618 gene 0:32 The Aeromonas caviae AHA0618 gene modulates cell length and influences swimming and swarming motility. 25515520 0 93 dep Aeromonas 4:12 arg1 caviae 14:19 caviae 14:19 caviae 14:19 The Aeromonas caviae AHA0618 gene modulates cell length and influences swimming and swarming motility. 25515520 6 94 theme pathogen 973:980 arg1 pylori 995:1000 the human pathogen Helicobacter pylori 963:1000 the human pathogen Helicobacter pylori 963:1000 Here, we investigated the role of the AHA0618 gene, which shares homology (37% at the amino acid level) with the central region of a putative deglycosylation enzyme (HP0518) from the human pathogen Helicobacter pylori, which also glycosylates its flagellin and is proposed to be part of a flagellin deglycosylation pathway. 25515520 7 95 dep A. 1142:1143 arg1 caviae 1145:1150 caviae 1145:1150 caviae 1145:1150 Phenotypic analysis of an AHA0618 A. caviae mutant revealed increased swimming and swarming motility compared to the wild-type strain but without any detectable effects on the glycosylation status of the polar flagellins when analyzed by western blot analysis or mass spectroscopy. 25515520 2 96 contain has 264:266 arg2 role 270:273 a role 268:273 a role 268:273 The polar flagellum also has a role in cellular adherence and biofilm formation. 25515520 2 96 contain has 264:266 arg1 flagellum 249:257 The polar flagellum 239:257 The polar flagellum 239:257 The polar flagellum also has a role in cellular adherence and biofilm formation. 25515520 6 97 theme gene 830:833 arg1 role 810:813 the role 806:813 the role of the AHA0618 gene, which shares homology (37% at the amino acid level) with the central region of a putative deglycosylation enzyme (HP0518) from the human pathogen Helicobacter pylori, which also glycosylates its flagellin and is proposed to be part of a flagellin deglycosylation pathway 806:1105 Here, we investigated the role of the AHA0618 gene, which shares homology (37% at the amino acid level) with the central region of a putative deglycosylation enzyme (HP0518) from the human pathogen Helicobacter pylori, which also glycosylates its flagellin and is proposed to be part of a flagellin deglycosylation pathway. 25515520 8 98 theme wall 1511:1514 arg1 biology 1516:1522 cell wall biology 1506:1522 cell wall biology 1506:1522 Bioinformatic analysis of the protein AHA0618, demonstrated homology to a family of l,d-transpeptidases involved in cell wall biology and peptidoglycan cross-linking (YkuD-like). 25515520 3 99 gly glycosylation 421:433 arg1 threonine 475:483 threonine 475:483 threonine 475:483 The two subunits of the polar flagellum, FlaA and FlaB, are posttranslationally modified by O-linked glycosylation with pseudaminic acid on 6-8 serine and threonine residues within the central region of these proteins. 25515520 3 99 gly glycosylation 421:433 arg1 serine 464:469 6-8 serine 460:469 6-8 serine 460:469 The two subunits of the polar flagellum, FlaA and FlaB, are posttranslationally modified by O-linked glycosylation with pseudaminic acid on 6-8 serine and threonine residues within the central region of these proteins. 25515520 3 100 theme O-linked 412:419 arg1 glycosylation 421:433 O-linked glycosylation 412:433 O-linked glycosylation with pseudaminic acid on 6-8 serine and threonine residues within the central region of these proteins 412:536 The two subunits of the polar flagellum, FlaA and FlaB, are posttranslationally modified by O-linked glycosylation with pseudaminic acid on 6-8 serine and threonine residues within the central region of these proteins. 25515520 3 101 from glycosylation 421:433 arg1 threonine 475:483 threonine 475:483 threonine 475:483 The two subunits of the polar flagellum, FlaA and FlaB, are posttranslationally modified by O-linked glycosylation with pseudaminic acid on 6-8 serine and threonine residues within the central region of these proteins. 25515520 3 101 from glycosylation 421:433 arg1 serine 464:469 6-8 serine 460:469 6-8 serine 460:469 The two subunits of the polar flagellum, FlaA and FlaB, are posttranslationally modified by O-linked glycosylation with pseudaminic acid on 6-8 serine and threonine residues within the central region of these proteins. 25515520 2 102 theme biofilm 301:307 arg1 formation 309:317 biofilm formation 301:317 biofilm formation 301:317 The polar flagellum also has a role in cellular adherence and biofilm formation. 25515520 7 103 theme swarming 1191:1198 arg1 motility 1200:1207 swarming motility 1191:1207 swarming motility 1191:1207 Phenotypic analysis of an AHA0618 A. caviae mutant revealed increased swimming and swarming motility compared to the wild-type strain but without any detectable effects on the glycosylation status of the polar flagellins when analyzed by western blot analysis or mass spectroscopy. 25515520 8 104 theme cross-linking 1542:1554 arg1 family 1464:1469 a family 1462:1469 a family of l,d-transpeptidases involved in cell wall biology and peptidoglycan cross-linking (YkuD-like) 1462:1566 Bioinformatic analysis of the protein AHA0618, demonstrated homology to a family of l,d-transpeptidases involved in cell wall biology and peptidoglycan cross-linking (YkuD-like). 25515520 6 105 from level 881:885 arg1 % 861:861 37% 859:861 37% 859:861 Here, we investigated the role of the AHA0618 gene, which shares homology (37% at the amino acid level) with the central region of a putative deglycosylation enzyme (HP0518) from the human pathogen Helicobacter pylori, which also glycosylates its flagellin and is proposed to be part of a flagellin deglycosylation pathway. 25515520 9 106 theme Scanning 1569:1576 arg1 SEM 1599:1601 SEM 1599:1601 SEM 1599:1601 Scanning electron microscopy (SEM) and fluorescence microscopy analysis of the wild-type and AHA0618-mutant A. caviae strains revealed the mutant to be subtly but significantly shorter than wild-type cells; a phenomenon that could be recovered when either AHA0618 or H. pylori HP0518 were introduced. 25515520 9 106 theme Scanning 1569:1576 arg1 microscopy 1587:1596 Scanning electron microscopy 1569:1596 Scanning electron microscopy (SEM) 1569:1602 Scanning electron microscopy (SEM) and fluorescence microscopy analysis of the wild-type and AHA0618-mutant A. caviae strains revealed the mutant to be subtly but significantly shorter than wild-type cells; a phenomenon that could be recovered when either AHA0618 or H. pylori HP0518 were introduced. 25515520 5 107 contain possesses 623:631 arg2 set 646:648 the simplest set 633:648 the simplest set of genes required for bacterial glycosylation currently known 633:710 Aeromonas caviae possesses the simplest set of genes required for bacterial glycosylation currently known, with the putative glycosyltransferase, Maf1, being described recently. 25515520 5 107 contain possesses 623:631 arg1 caviae 616:621 Aeromonas caviae 606:621 Aeromonas caviae 606:621 Aeromonas caviae possesses the simplest set of genes required for bacterial glycosylation currently known, with the putative glycosyltransferase, Maf1, being described recently. 25515520 5 107 contain possesses 623:631 arg2 genes 653:657 genes 653:657 genes required for bacterial glycosylation currently known 653:710 Aeromonas caviae possesses the simplest set of genes required for bacterial glycosylation currently known, with the putative glycosyltransferase, Maf1, being described recently. 24762810 4 0 theme substrates 1003:1012 arg1 hundreds 983:990 hundreds 983:990 hundreds of protein substrates 983:1012 The enzymes responsible for O-GlcNAc addition and removal are encoded by a single pair of genes: both the O-GlcNAc transferase (OGT) and the O-GlcNAcase (OGA, also known as MGEA5) genes are alternatively spliced, producing protein variants that are targeted to discrete cellular locations where they must selectively recognize hundreds of protein substrates. 24762810 5 1 theme O-GlcNAc 1141:1148 arg1 cycling 1150:1156 anchor O-GlcNAc cycling 1134:1156 anchor O-GlcNAc cycling 1134:1156 Recent reports suggest that in addition to their catalytic functions, OGT and OGA use their multifunctional domains to anchor O-GlcNAc cycling to discrete intracellular sites, thus allowing them to establish gradients of deacetylase, kinase and phosphatase signaling activities. 24762810 5 2 theme activities 1282:1291 arg1 gradients 1223:1231 gradients 1223:1231 gradients of deacetylase, kinase and phosphatase signaling activities 1223:1291 Recent reports suggest that in addition to their catalytic functions, OGT and OGA use their multifunctional domains to anchor O-GlcNAc cycling to discrete intracellular sites, thus allowing them to establish gradients of deacetylase, kinase and phosphatase signaling activities. 24762810 4 3 theme protein 995:1001 arg1 substrates 1003:1012 protein substrates 995:1012 protein substrates 995:1012 The enzymes responsible for O-GlcNAc addition and removal are encoded by a single pair of genes: both the O-GlcNAc transferase (OGT) and the O-GlcNAcase (OGA, also known as MGEA5) genes are alternatively spliced, producing protein variants that are targeted to discrete cellular locations where they must selectively recognize hundreds of protein substrates. 24762810 7 4 from alterations 1668:1678 arg1 supply 1692:1697 nutrient supply 1683:1697 nutrient supply 1683:1697 As such, the tethering of the enzymes of O-GlcNAc cycling appears to play a role in ensuring proper spatiotemporal responses to global alterations in nutrient supply. 24762810 2 5 theme O-linked 368:375 arg1 addition 377:384 O-linked addition 368:384 O-linked addition of N-acetylglucosamine to serine and threonine residues 368:440 Mounting evidence suggests that one way this is achieved is through the establishment of physically defined gradients of O-GlcNAcylation (O-linked addition of N-acetylglucosamine to serine and threonine residues) and O-GlcNAc turnover. 24762810 6 6 theme lipid 1424:1428 arg1 remodeling 1438:1447 lipid droplet remodeling 1424:1447 lipid droplet remodeling 1424:1447 The localized signaling gradients established by targeted O-GlcNAc cycling influence many important cellular processes, including lipid droplet remodeling, mitochondrial functioning, epigenetic control of gene expression and proteostasis. 24762810 5 7 theme Recent 1015:1020 arg1 reports 1022:1028 Recent reports 1015:1028 Recent reports 1015:1028 Recent reports suggest that in addition to their catalytic functions, OGT and OGA use their multifunctional domains to anchor O-GlcNAc cycling to discrete intracellular sites, thus allowing them to establish gradients of deacetylase, kinase and phosphatase signaling activities. 24762810 6 8 theme signaling 1308:1316 arg1 gradients 1318:1326 The localized signaling gradients 1294:1326 The localized signaling gradients established by targeted O-GlcNAc cycling 1294:1367 The localized signaling gradients established by targeted O-GlcNAc cycling influence many important cellular processes, including lipid droplet remodeling, mitochondrial functioning, epigenetic control of gene expression and proteostasis. 24762810 2 9 dep O-GlcNAcylation 351:365 arg1 addition 377:384 O-linked addition 368:384 O-linked addition of N-acetylglucosamine to serine and threonine residues 368:440 Mounting evidence suggests that one way this is achieved is through the establishment of physically defined gradients of O-GlcNAcylation (O-linked addition of N-acetylglucosamine to serine and threonine residues) and O-GlcNAc turnover. 24762810 4 10 theme transferase 771:781 arg1 genes 836:840 both the O-GlcNAc transferase (OGT) and the O-GlcNAcase (OGA, also known as MGEA5) genes 753:840 both the O-GlcNAc transferase (OGT) and the O-GlcNAcase (OGA, also known as MGEA5) genes 753:840 The enzymes responsible for O-GlcNAc addition and removal are encoded by a single pair of genes: both the O-GlcNAc transferase (OGT) and the O-GlcNAcase (OGA, also known as MGEA5) genes are alternatively spliced, producing protein variants that are targeted to discrete cellular locations where they must selectively recognize hundreds of protein substrates. 24762810 4 11 theme protein 879:885 arg1 variants 887:894 protein variants 879:894 protein variants that are targeted to discrete cellular locations where they must selectively recognize hundreds of protein substrates 879:1012 The enzymes responsible for O-GlcNAc addition and removal are encoded by a single pair of genes: both the O-GlcNAc transferase (OGT) and the O-GlcNAcase (OGA, also known as MGEA5) genes are alternatively spliced, producing protein variants that are targeted to discrete cellular locations where they must selectively recognize hundreds of protein substrates. 24762810 6 12 theme localized 1298:1306 arg1 gradients 1318:1326 The localized signaling gradients 1294:1326 The localized signaling gradients established by targeted O-GlcNAc cycling 1294:1367 The localized signaling gradients established by targeted O-GlcNAc cycling influence many important cellular processes, including lipid droplet remodeling, mitochondrial functioning, epigenetic control of gene expression and proteostasis. 24762810 3 13 theme nutrient-responsive 518:536 arg1 pathway 559:565 the nutrient-responsive hexosamine signaling pathway 514:565 the nutrient-responsive hexosamine signaling pathway 514:565 Because O-GlcNAcylation levels are dependent on the nutrient-responsive hexosamine signaling pathway, this modification is uniquely poised to inform upon the nutritive state of an organism. 24762810 2 14 link O-linked 368:375 arg1 addition 377:384 O-linked addition 368:384 O-linked addition of N-acetylglucosamine to serine and threonine residues 368:440 Mounting evidence suggests that one way this is achieved is through the establishment of physically defined gradients of O-GlcNAcylation (O-linked addition of N-acetylglucosamine to serine and threonine residues) and O-GlcNAc turnover. 24762810 7 15 theme proper 1626:1631 arg1 responses 1648:1656 proper spatiotemporal responses 1626:1656 proper spatiotemporal responses to global alterations in nutrient supply 1626:1697 As such, the tethering of the enzymes of O-GlcNAc cycling appears to play a role in ensuring proper spatiotemporal responses to global alterations in nutrient supply. 24762810 4 16 theme O-GlcNAcase 797:807 arg1 genes 836:840 both the O-GlcNAc transferase (OGT) and the O-GlcNAcase (OGA, also known as MGEA5) genes 753:840 both the O-GlcNAc transferase (OGT) and the O-GlcNAcase (OGA, also known as MGEA5) genes 753:840 The enzymes responsible for O-GlcNAc addition and removal are encoded by a single pair of genes: both the O-GlcNAc transferase (OGT) and the O-GlcNAcase (OGA, also known as MGEA5) genes are alternatively spliced, producing protein variants that are targeted to discrete cellular locations where they must selectively recognize hundreds of protein substrates. 24762810 2 17 dep way 266:268 arg1 achieved 278:285 achieved 278:285 is achieved 275:285 Mounting evidence suggests that one way this is achieved is through the establishment of physically defined gradients of O-GlcNAcylation (O-linked addition of N-acetylglucosamine to serine and threonine residues) and O-GlcNAc turnover. 24762810 5 18 theme deacetylase 1236:1246 arg1 activities 1282:1291 deacetylase, kinase and phosphatase signaling activities 1236:1291 activities 1282:1291 Recent reports suggest that in addition to their catalytic functions, OGT and OGA use their multifunctional domains to anchor O-GlcNAc cycling to discrete intracellular sites, thus allowing them to establish gradients of deacetylase, kinase and phosphatase signaling activities. 24762810 7 19 theme spatiotemporal 1633:1646 arg1 responses 1648:1656 proper spatiotemporal responses 1626:1656 proper spatiotemporal responses to global alterations in nutrient supply 1626:1697 As such, the tethering of the enzymes of O-GlcNAc cycling appears to play a role in ensuring proper spatiotemporal responses to global alterations in nutrient supply. 24762810 6 20 theme expression 1504:1513 arg1 remodeling 1438:1447 lipid droplet remodeling 1424:1447 lipid droplet remodeling 1424:1447 The localized signaling gradients established by targeted O-GlcNAc cycling influence many important cellular processes, including lipid droplet remodeling, mitochondrial functioning, epigenetic control of gene expression and proteostasis. 24762810 6 20 theme expression 1504:1513 arg1 proteostasis 1519:1530 proteostasis 1519:1530 proteostasis 1519:1530 The localized signaling gradients established by targeted O-GlcNAc cycling influence many important cellular processes, including lipid droplet remodeling, mitochondrial functioning, epigenetic control of gene expression and proteostasis. 24762810 6 20 theme expression 1504:1513 arg1 control 1488:1494 epigenetic control 1477:1494 epigenetic control of gene expression 1477:1513 The localized signaling gradients established by targeted O-GlcNAc cycling influence many important cellular processes, including lipid droplet remodeling, mitochondrial functioning, epigenetic control of gene expression and proteostasis. 24762810 3 21 theme O-GlcNAcylation 474:488 arg1 levels 490:495 O-GlcNAcylation levels 474:495 O-GlcNAcylation levels 474:495 Because O-GlcNAcylation levels are dependent on the nutrient-responsive hexosamine signaling pathway, this modification is uniquely poised to inform upon the nutritive state of an organism. 24762810 0 22 theme O-GlcNAc 16:23 arg1 cycling 25:31 Nutrient-driven O-GlcNAc cycling 0:31 Nutrient-driven O-GlcNAc cycling - think globally but act locally. 0:65 Nutrient-driven O-GlcNAc cycling - think globally but act locally. 24762810 6 23 theme droplet 1430:1436 arg1 remodeling 1438:1447 lipid droplet remodeling 1424:1447 lipid droplet remodeling 1424:1447 The localized signaling gradients established by targeted O-GlcNAc cycling influence many important cellular processes, including lipid droplet remodeling, mitochondrial functioning, epigenetic control of gene expression and proteostasis. 24762810 2 24 theme defined 330:336 arg1 gradients 338:346 physically defined gradients 319:346 physically defined gradients of O-GlcNAcylation (O-linked addition of N-acetylglucosamine to serine and threonine residues) and O-GlcNAc turnover 319:463 Mounting evidence suggests that one way this is achieved is through the establishment of physically defined gradients of O-GlcNAcylation (O-linked addition of N-acetylglucosamine to serine and threonine residues) and O-GlcNAc turnover. 24762810 5 25 theme multifunctional 1107:1121 arg1 domains 1123:1129 their multifunctional domains 1101:1129 their multifunctional domains 1101:1129 Recent reports suggest that in addition to their catalytic functions, OGT and OGA use their multifunctional domains to anchor O-GlcNAc cycling to discrete intracellular sites, thus allowing them to establish gradients of deacetylase, kinase and phosphatase signaling activities. 24762810 1 26 theme global 189:194 arg1 changes 196:202 global changes 189:202 global changes in nutrient availability 189:227 Proper cellular functioning requires that cellular machinery behave in a spatiotemporally regulated manner in response to global changes in nutrient availability. 24762810 0 27 theme Nutrient-driven 0:14 arg1 cycling 25:31 Nutrient-driven O-GlcNAc cycling 0:31 Nutrient-driven O-GlcNAc cycling - think globally but act locally. 0:65 Nutrient-driven O-GlcNAc cycling - think globally but act locally. 24762810 6 28 theme cellular 1394:1401 arg1 remodeling 1438:1447 lipid droplet remodeling 1424:1447 lipid droplet remodeling 1424:1447 The localized signaling gradients established by targeted O-GlcNAc cycling influence many important cellular processes, including lipid droplet remodeling, mitochondrial functioning, epigenetic control of gene expression and proteostasis. 24762810 6 28 theme cellular 1394:1401 arg1 processes 1403:1411 many important cellular processes 1379:1411 many important cellular processes 1379:1411 The localized signaling gradients established by targeted O-GlcNAc cycling influence many important cellular processes, including lipid droplet remodeling, mitochondrial functioning, epigenetic control of gene expression and proteostasis. 24762810 6 28 theme cellular 1394:1401 arg1 control 1488:1494 epigenetic control 1477:1494 epigenetic control of gene expression 1477:1513 The localized signaling gradients established by targeted O-GlcNAc cycling influence many important cellular processes, including lipid droplet remodeling, mitochondrial functioning, epigenetic control of gene expression and proteostasis. 24762810 6 28 theme cellular 1394:1401 arg1 proteostasis 1519:1530 proteostasis 1519:1530 proteostasis 1519:1530 The localized signaling gradients established by targeted O-GlcNAc cycling influence many important cellular processes, including lipid droplet remodeling, mitochondrial functioning, epigenetic control of gene expression and proteostasis. 24762810 6 28 theme cellular 1394:1401 arg1 mitochondrial 1450:1462 mitochondrial 1450:1462 mitochondrial 1450:1462 The localized signaling gradients established by targeted O-GlcNAc cycling influence many important cellular processes, including lipid droplet remodeling, mitochondrial functioning, epigenetic control of gene expression and proteostasis. 24762810 3 29 theme nutritive 624:632 arg1 state 634:638 the nutritive state 620:638 the nutritive state of an organism 620:653 Because O-GlcNAcylation levels are dependent on the nutrient-responsive hexosamine signaling pathway, this modification is uniquely poised to inform upon the nutritive state of an organism. 24762810 6 30 theme important 1384:1392 arg1 remodeling 1438:1447 lipid droplet remodeling 1424:1447 lipid droplet remodeling 1424:1447 The localized signaling gradients established by targeted O-GlcNAc cycling influence many important cellular processes, including lipid droplet remodeling, mitochondrial functioning, epigenetic control of gene expression and proteostasis. 24762810 6 30 theme important 1384:1392 arg1 processes 1403:1411 many important cellular processes 1379:1411 many important cellular processes 1379:1411 The localized signaling gradients established by targeted O-GlcNAc cycling influence many important cellular processes, including lipid droplet remodeling, mitochondrial functioning, epigenetic control of gene expression and proteostasis. 24762810 6 30 theme important 1384:1392 arg1 control 1488:1494 epigenetic control 1477:1494 epigenetic control of gene expression 1477:1513 The localized signaling gradients established by targeted O-GlcNAc cycling influence many important cellular processes, including lipid droplet remodeling, mitochondrial functioning, epigenetic control of gene expression and proteostasis. 24762810 6 30 theme important 1384:1392 arg1 proteostasis 1519:1530 proteostasis 1519:1530 proteostasis 1519:1530 The localized signaling gradients established by targeted O-GlcNAc cycling influence many important cellular processes, including lipid droplet remodeling, mitochondrial functioning, epigenetic control of gene expression and proteostasis. 24762810 6 30 theme important 1384:1392 arg1 mitochondrial 1450:1462 mitochondrial 1450:1462 mitochondrial 1450:1462 The localized signaling gradients established by targeted O-GlcNAc cycling influence many important cellular processes, including lipid droplet remodeling, mitochondrial functioning, epigenetic control of gene expression and proteostasis. 24762810 6 31 theme gene 1499:1502 arg1 expression 1504:1513 gene expression 1499:1513 gene expression 1499:1513 The localized signaling gradients established by targeted O-GlcNAc cycling influence many important cellular processes, including lipid droplet remodeling, mitochondrial functioning, epigenetic control of gene expression and proteostasis. 24762810 4 32 theme O-GlcNAc 762:769 arg1 OGT 784:786 OGT 784:786 OGT 784:786 The enzymes responsible for O-GlcNAc addition and removal are encoded by a single pair of genes: both the O-GlcNAc transferase (OGT) and the O-GlcNAcase (OGA, also known as MGEA5) genes are alternatively spliced, producing protein variants that are targeted to discrete cellular locations where they must selectively recognize hundreds of protein substrates. 24762810 4 32 theme O-GlcNAc 762:769 arg1 transferase 771:781 the O-GlcNAc transferase 758:781 the O-GlcNAc transferase (OGT) 758:787 The enzymes responsible for O-GlcNAc addition and removal are encoded by a single pair of genes: both the O-GlcNAc transferase (OGT) and the O-GlcNAcase (OGA, also known as MGEA5) genes are alternatively spliced, producing protein variants that are targeted to discrete cellular locations where they must selectively recognize hundreds of protein substrates. 24762810 4 33 theme cellular 926:933 arg1 locations 935:943 discrete cellular locations 917:943 discrete cellular locations where they must selectively recognize hundreds of protein substrates 917:1012 The enzymes responsible for O-GlcNAc addition and removal are encoded by a single pair of genes: both the O-GlcNAc transferase (OGT) and the O-GlcNAcase (OGA, also known as MGEA5) genes are alternatively spliced, producing protein variants that are targeted to discrete cellular locations where they must selectively recognize hundreds of protein substrates. 24762810 2 34 theme O-GlcNAc 447:454 arg1 turnover 456:463 O-GlcNAc turnover 447:463 O-GlcNAc turnover 447:463 Mounting evidence suggests that one way this is achieved is through the establishment of physically defined gradients of O-GlcNAcylation (O-linked addition of N-acetylglucosamine to serine and threonine residues) and O-GlcNAc turnover. 24762810 2 35 theme turnover 456:463 arg1 gradients 338:346 physically defined gradients 319:346 physically defined gradients of O-GlcNAcylation (O-linked addition of N-acetylglucosamine to serine and threonine residues) and O-GlcNAc turnover 319:463 Mounting evidence suggests that one way this is achieved is through the establishment of physically defined gradients of O-GlcNAcylation (O-linked addition of N-acetylglucosamine to serine and threonine residues) and O-GlcNAc turnover. 24762810 4 36 theme discrete 917:924 arg1 locations 935:943 discrete cellular locations 917:943 discrete cellular locations where they must selectively recognize hundreds of protein substrates 917:1012 The enzymes responsible for O-GlcNAc addition and removal are encoded by a single pair of genes: both the O-GlcNAc transferase (OGT) and the O-GlcNAcase (OGA, also known as MGEA5) genes are alternatively spliced, producing protein variants that are targeted to discrete cellular locations where they must selectively recognize hundreds of protein substrates. 24762810 1 37 theme cellular 109:116 arg1 machinery 118:126 cellular machinery 109:126 cellular machinery 109:126 Proper cellular functioning requires that cellular machinery behave in a spatiotemporally regulated manner in response to global changes in nutrient availability. 24762810 1 38 theme nutrient 207:214 arg1 availability 216:227 nutrient availability 207:227 nutrient availability 207:227 Proper cellular functioning requires that cellular machinery behave in a spatiotemporally regulated manner in response to global changes in nutrient availability. 24762810 3 39 theme signaling 549:557 arg1 pathway 559:565 the nutrient-responsive hexosamine signaling pathway 514:565 the nutrient-responsive hexosamine signaling pathway 514:565 Because O-GlcNAcylation levels are dependent on the nutrient-responsive hexosamine signaling pathway, this modification is uniquely poised to inform upon the nutritive state of an organism. 24762810 6 40 theme many 1379:1382 arg1 remodeling 1438:1447 lipid droplet remodeling 1424:1447 lipid droplet remodeling 1424:1447 The localized signaling gradients established by targeted O-GlcNAc cycling influence many important cellular processes, including lipid droplet remodeling, mitochondrial functioning, epigenetic control of gene expression and proteostasis. 24762810 6 40 theme many 1379:1382 arg1 processes 1403:1411 many important cellular processes 1379:1411 many important cellular processes 1379:1411 The localized signaling gradients established by targeted O-GlcNAc cycling influence many important cellular processes, including lipid droplet remodeling, mitochondrial functioning, epigenetic control of gene expression and proteostasis. 24762810 6 40 theme many 1379:1382 arg1 control 1488:1494 epigenetic control 1477:1494 epigenetic control of gene expression 1477:1513 The localized signaling gradients established by targeted O-GlcNAc cycling influence many important cellular processes, including lipid droplet remodeling, mitochondrial functioning, epigenetic control of gene expression and proteostasis. 24762810 6 40 theme many 1379:1382 arg1 proteostasis 1519:1530 proteostasis 1519:1530 proteostasis 1519:1530 The localized signaling gradients established by targeted O-GlcNAc cycling influence many important cellular processes, including lipid droplet remodeling, mitochondrial functioning, epigenetic control of gene expression and proteostasis. 24762810 6 40 theme many 1379:1382 arg1 mitochondrial 1450:1462 mitochondrial 1450:1462 mitochondrial 1450:1462 The localized signaling gradients established by targeted O-GlcNAc cycling influence many important cellular processes, including lipid droplet remodeling, mitochondrial functioning, epigenetic control of gene expression and proteostasis. 24762810 7 41 theme O-GlcNAc 1574:1581 arg1 cycling 1583:1589 O-GlcNAc cycling 1574:1589 O-GlcNAc cycling 1574:1589 As such, the tethering of the enzymes of O-GlcNAc cycling appears to play a role in ensuring proper spatiotemporal responses to global alterations in nutrient supply. 24762810 4 42 theme single 731:736 arg1 pair 738:741 a single pair 729:741 a single pair of genes 729:750 The enzymes responsible for O-GlcNAc addition and removal are encoded by a single pair of genes: both the O-GlcNAc transferase (OGT) and the O-GlcNAcase (OGA, also known as MGEA5) genes are alternatively spliced, producing protein variants that are targeted to discrete cellular locations where they must selectively recognize hundreds of protein substrates. 24762810 5 43 theme discrete 1161:1168 arg1 sites 1184:1188 discrete intracellular sites 1161:1188 discrete intracellular sites 1161:1188 Recent reports suggest that in addition to their catalytic functions, OGT and OGA use their multifunctional domains to anchor O-GlcNAc cycling to discrete intracellular sites, thus allowing them to establish gradients of deacetylase, kinase and phosphatase signaling activities. 24762810 6 44 theme epigenetic 1477:1486 arg1 control 1488:1494 epigenetic control 1477:1494 epigenetic control of gene expression 1477:1513 The localized signaling gradients established by targeted O-GlcNAc cycling influence many important cellular processes, including lipid droplet remodeling, mitochondrial functioning, epigenetic control of gene expression and proteostasis. 24762810 7 45 theme cycling 1583:1589 arg1 enzymes 1563:1569 the enzymes 1559:1569 the enzymes of O-GlcNAc cycling 1559:1589 As such, the tethering of the enzymes of O-GlcNAc cycling appears to play a role in ensuring proper spatiotemporal responses to global alterations in nutrient supply. 24762810 1 46 dep changes 196:202 arg1 response 177:184 response 177:184 response 177:184 Proper cellular functioning requires that cellular machinery behave in a spatiotemporally regulated manner in response to global changes in nutrient availability. 24762810 4 47 dep O-GlcNAcase 797:807 arg1 OGA 810:812 OGA 810:812 OGA 810:812 The enzymes responsible for O-GlcNAc addition and removal are encoded by a single pair of genes: both the O-GlcNAc transferase (OGT) and the O-GlcNAcase (OGA, also known as MGEA5) genes are alternatively spliced, producing protein variants that are targeted to discrete cellular locations where they must selectively recognize hundreds of protein substrates. 24762810 5 48 theme intracellular 1170:1182 arg1 sites 1184:1188 discrete intracellular sites 1161:1188 discrete intracellular sites 1161:1188 Recent reports suggest that in addition to their catalytic functions, OGT and OGA use their multifunctional domains to anchor O-GlcNAc cycling to discrete intracellular sites, thus allowing them to establish gradients of deacetylase, kinase and phosphatase signaling activities. 24762810 5 49 theme phosphatase 1260:1270 arg1 activities 1282:1291 deacetylase, kinase and phosphatase signaling activities 1236:1291 activities 1282:1291 Recent reports suggest that in addition to their catalytic functions, OGT and OGA use their multifunctional domains to anchor O-GlcNAc cycling to discrete intracellular sites, thus allowing them to establish gradients of deacetylase, kinase and phosphatase signaling activities. 24762810 3 50 theme hexosamine 538:547 arg1 pathway 559:565 the nutrient-responsive hexosamine signaling pathway 514:565 the nutrient-responsive hexosamine signaling pathway 514:565 Because O-GlcNAcylation levels are dependent on the nutrient-responsive hexosamine signaling pathway, this modification is uniquely poised to inform upon the nutritive state of an organism. 24762810 7 51 theme global 1661:1666 arg1 alterations 1668:1678 global alterations 1661:1678 global alterations in nutrient supply 1661:1697 As such, the tethering of the enzymes of O-GlcNAc cycling appears to play a role in ensuring proper spatiotemporal responses to global alterations in nutrient supply. 24762810 6 52 theme O-GlcNAc 1352:1359 arg1 cycling 1361:1367 targeted O-GlcNAc cycling 1343:1367 targeted O-GlcNAc cycling 1343:1367 The localized signaling gradients established by targeted O-GlcNAc cycling influence many important cellular processes, including lipid droplet remodeling, mitochondrial functioning, epigenetic control of gene expression and proteostasis. 24762810 2 53 theme Mounting 230:237 arg1 evidence 239:246 Mounting evidence 230:246 Mounting evidence 230:246 Mounting evidence suggests that one way this is achieved is through the establishment of physically defined gradients of O-GlcNAcylation (O-linked addition of N-acetylglucosamine to serine and threonine residues) and O-GlcNAc turnover. 24762810 2 54 theme O-GlcNAcylation 351:365 arg1 gradients 338:346 physically defined gradients 319:346 physically defined gradients of O-GlcNAcylation (O-linked addition of N-acetylglucosamine to serine and threonine residues) and O-GlcNAc turnover 319:463 Mounting evidence suggests that one way this is achieved is through the establishment of physically defined gradients of O-GlcNAcylation (O-linked addition of N-acetylglucosamine to serine and threonine residues) and O-GlcNAc turnover. 24762810 6 55 theme targeted 1343:1350 arg1 cycling 1361:1367 targeted O-GlcNAc cycling 1343:1367 targeted O-GlcNAc cycling 1343:1367 The localized signaling gradients established by targeted O-GlcNAc cycling influence many important cellular processes, including lipid droplet remodeling, mitochondrial functioning, epigenetic control of gene expression and proteostasis. 24762810 5 56 theme catalytic 1064:1072 arg1 functions 1074:1082 their catalytic functions 1058:1082 their catalytic functions 1058:1082 Recent reports suggest that in addition to their catalytic functions, OGT and OGA use their multifunctional domains to anchor O-GlcNAc cycling to discrete intracellular sites, thus allowing them to establish gradients of deacetylase, kinase and phosphatase signaling activities. 24762810 2 57 dep serine 412:417 arg1 residues 433:440 residues 433:440 residues 433:440 Mounting evidence suggests that one way this is achieved is through the establishment of physically defined gradients of O-GlcNAcylation (O-linked addition of N-acetylglucosamine to serine and threonine residues) and O-GlcNAc turnover. 24762810 3 58 theme organism 646:653 arg1 state 634:638 the nutritive state 620:638 the nutritive state of an organism 620:653 Because O-GlcNAcylation levels are dependent on the nutrient-responsive hexosamine signaling pathway, this modification is uniquely poised to inform upon the nutritive state of an organism. 24762810 0 59 dep cycling 25:31 arg1 think 35:39 think 35:39 think globally 35:48 Nutrient-driven O-GlcNAc cycling - think globally but act locally. 24762810 0 59 dep cycling 25:31 arg1 act 54:56 act 54:56 act locally 54:64 Nutrient-driven O-GlcNAc cycling - think globally but act locally. 24762810 7 60 theme nutrient 1683:1690 arg1 supply 1692:1697 nutrient supply 1683:1697 nutrient supply 1683:1697 As such, the tethering of the enzymes of O-GlcNAc cycling appears to play a role in ensuring proper spatiotemporal responses to global alterations in nutrient supply. 24762810 2 61 theme gradients 338:346 arg1 establishment 302:314 the establishment 298:314 the establishment of physically defined gradients of O-GlcNAcylation (O-linked addition of N-acetylglucosamine to serine and threonine residues) and O-GlcNAc turnover 298:463 Mounting evidence suggests that one way this is achieved is through the establishment of physically defined gradients of O-GlcNAcylation (O-linked addition of N-acetylglucosamine to serine and threonine residues) and O-GlcNAc turnover. 24762810 5 62 theme kinase 1249:1254 arg1 activities 1282:1291 deacetylase, kinase and phosphatase signaling activities 1236:1291 activities 1282:1291 Recent reports suggest that in addition to their catalytic functions, OGT and OGA use their multifunctional domains to anchor O-GlcNAc cycling to discrete intracellular sites, thus allowing them to establish gradients of deacetylase, kinase and phosphatase signaling activities. 24762810 7 63 theme enzymes 1563:1569 arg1 tethering 1546:1554 the tethering 1542:1554 the tethering of the enzymes of O-GlcNAc cycling 1542:1589 As such, the tethering of the enzymes of O-GlcNAc cycling appears to play a role in ensuring proper spatiotemporal responses to global alterations in nutrient supply. 24762810 1 64 from changes 196:202 arg1 availability 216:227 nutrient availability 207:227 nutrient availability 207:227 Proper cellular functioning requires that cellular machinery behave in a spatiotemporally regulated manner in response to global changes in nutrient availability. 24762810 2 65 theme N-acetylglucosamine 389:407 arg1 addition 377:384 O-linked addition 368:384 O-linked addition of N-acetylglucosamine to serine and threonine residues 368:440 Mounting evidence suggests that one way this is achieved is through the establishment of physically defined gradients of O-GlcNAcylation (O-linked addition of N-acetylglucosamine to serine and threonine residues) and O-GlcNAc turnover. 24762810 4 66 theme responsible 668:678 arg1 enzymes 660:666 The enzymes 656:666 The enzymes responsible for O-GlcNAc addition and removal 656:712 The enzymes responsible for O-GlcNAc addition and removal are encoded by a single pair of genes: both the O-GlcNAc transferase (OGT) and the O-GlcNAcase (OGA, also known as MGEA5) genes are alternatively spliced, producing protein variants that are targeted to discrete cellular locations where they must selectively recognize hundreds of protein substrates. 24762810 5 67 theme anchor 1134:1139 arg1 cycling 1150:1156 anchor O-GlcNAc cycling 1134:1156 anchor O-GlcNAc cycling 1134:1156 Recent reports suggest that in addition to their catalytic functions, OGT and OGA use their multifunctional domains to anchor O-GlcNAc cycling to discrete intracellular sites, thus allowing them to establish gradients of deacetylase, kinase and phosphatase signaling activities. 24762810 4 68 theme O-GlcNAc 684:691 arg1 addition 693:700 O-GlcNAc addition 684:700 O-GlcNAc addition 684:700 The enzymes responsible for O-GlcNAc addition and removal are encoded by a single pair of genes: both the O-GlcNAc transferase (OGT) and the O-GlcNAcase (OGA, also known as MGEA5) genes are alternatively spliced, producing protein variants that are targeted to discrete cellular locations where they must selectively recognize hundreds of protein substrates. 24762810 1 69 theme regulated 157:165 arg1 manner 167:172 a spatiotemporally regulated manner 138:172 a spatiotemporally regulated manner 138:172 Proper cellular functioning requires that cellular machinery behave in a spatiotemporally regulated manner in response to global changes in nutrient availability. 24762810 5 70 theme signaling 1272:1280 arg1 activities 1282:1291 deacetylase, kinase and phosphatase signaling activities 1236:1291 activities 1282:1291 Recent reports suggest that in addition to their catalytic functions, OGT and OGA use their multifunctional domains to anchor O-GlcNAc cycling to discrete intracellular sites, thus allowing them to establish gradients of deacetylase, kinase and phosphatase signaling activities. 24762810 4 71 theme genes 746:750 arg1 pair 738:741 a single pair 729:741 a single pair of genes 729:750 The enzymes responsible for O-GlcNAc addition and removal are encoded by a single pair of genes: both the O-GlcNAc transferase (OGT) and the O-GlcNAcase (OGA, also known as MGEA5) genes are alternatively spliced, producing protein variants that are targeted to discrete cellular locations where they must selectively recognize hundreds of protein substrates. 24733390 0 0 theme O-linked 79:86 arg1 β-1,2-N-acetlyglucosaminyltransferase 96:132 protein O-linked mannose β-1,2-N-acetlyglucosaminyltransferase 1 71:134 protein O-linked mannose β-1,2-N-acetlyglucosaminyltransferase 1 71:134 Golgi phosphoprotein 3 mediates the Golgi localization and function of protein O-linked mannose β-1,2-N-acetlyglucosaminyltransferase 1. 24733390 4 1 theme cytoplasmic 589:599 arg1 tail 601:604 The cytoplasmic tail 585:604 The cytoplasmic tail of POMGnT1 585:615 The cytoplasmic tail of POMGnT1 was found to be critical for mediating its interaction with GOLPH3. 24733390 4 1 theme cytoplasmic 589:599 arg1 critical 633:640 critical 633:640 critical 633:640 The cytoplasmic tail of POMGnT1 was found to be critical for mediating its interaction with GOLPH3. 24733390 0 2 theme protein 71:77 arg1 β-1,2-N-acetlyglucosaminyltransferase 96:132 protein O-linked mannose β-1,2-N-acetlyglucosaminyltransferase 1 71:134 protein O-linked mannose β-1,2-N-acetlyglucosaminyltransferase 1 71:134 Golgi phosphoprotein 3 mediates the Golgi localization and function of protein O-linked mannose β-1,2-N-acetlyglucosaminyltransferase 1. 24733390 6 3 theme stem 911:914 arg1 POMGnT1 926:932 POMGnT1 926:932 POMGnT1 926:932 In addition, we showed that three clinically relevant mutations present in the stem domain of POMGnT1 mislocalized to the endoplasmic reticulum, highlighting the importance of identifying the molecular mechanisms responsible for Golgi localization of glycosyltransferases. 24733390 6 3 theme stem 911:914 arg1 domain 916:921 the stem domain 907:921 the stem domain of POMGnT1 907:932 In addition, we showed that three clinically relevant mutations present in the stem domain of POMGnT1 mislocalized to the endoplasmic reticulum, highlighting the importance of identifying the molecular mechanisms responsible for Golgi localization of glycosyltransferases. 24733390 0 4 theme β-1,2-N-acetlyglucosaminyltransferase 96:132 arg1 function 59:66 function 59:66 function 59:66 Golgi phosphoprotein 3 mediates the Golgi localization and function of protein O-linked mannose β-1,2-N-acetlyglucosaminyltransferase 1. 24733390 0 4 theme β-1,2-N-acetlyglucosaminyltransferase 96:132 arg1 localization 42:53 Golgi localization 36:53 Golgi localization 36:53 Golgi phosphoprotein 3 mediates the Golgi localization and function of protein O-linked mannose β-1,2-N-acetlyglucosaminyltransferase 1. 24733390 2 5 theme mannosyltransferases 301:320 arg1 localization 277:288 the Golgi localization 267:288 the Golgi localization of several mannosyltransferases, which is subsequently critical for N- and O-glycosylation in yeast 267:388 The yeast homolog, Vps74p, interacts with and maintains the Golgi localization of several mannosyltransferases, which is subsequently critical for N- and O-glycosylation in yeast. 24733390 0 6 theme mannose 88:94 arg1 β-1,2-N-acetlyglucosaminyltransferase 96:132 protein O-linked mannose β-1,2-N-acetlyglucosaminyltransferase 1 71:134 protein O-linked mannose β-1,2-N-acetlyglucosaminyltransferase 1 71:134 Golgi phosphoprotein 3 mediates the Golgi localization and function of protein O-linked mannose β-1,2-N-acetlyglucosaminyltransferase 1. 24733390 6 7 from domain 916:921 arg1 present 896:902 present 896:902 present 896:902 In addition, we showed that three clinically relevant mutations present in the stem domain of POMGnT1 mislocalized to the endoplasmic reticulum, highlighting the importance of identifying the molecular mechanisms responsible for Golgi localization of glycosyltransferases. 24733390 2 8 theme several 293:299 arg1 mannosyltransferases 301:320 several mannosyltransferases 293:320 several mannosyltransferases 293:320 The yeast homolog, Vps74p, interacts with and maintains the Golgi localization of several mannosyltransferases, which is subsequently critical for N- and O-glycosylation in yeast. 24733390 5 9 theme POMGnT1 739:745 arg1 inability 726:734 the inability 722:734 the inability of POMGnT1 to localize to the Golgi 722:770 Loss of this interaction resulted in the inability of POMGnT1 to localize to the Golgi and reduced the functional glycosylation of α-dystroglycan. 24733390 6 10 theme present 896:902 arg1 mutations 886:894 three clinically relevant mutations 860:894 three clinically relevant mutations present in the stem domain of POMGnT1 860:932 In addition, we showed that three clinically relevant mutations present in the stem domain of POMGnT1 mislocalized to the endoplasmic reticulum, highlighting the importance of identifying the molecular mechanisms responsible for Golgi localization of glycosyltransferases. 24733390 7 11 theme novel 1127:1131 arg1 role 1133:1136 a novel role 1125:1136 a novel role for GOLPH3 in mediating the Golgi localization of POMGnT1 1125:1194 Our findings reveal a novel role for GOLPH3 in mediating the Golgi localization of POMGnT1. 24733390 2 12 from N- 358:359 arg1 yeast 384:388 yeast 384:388 yeast 384:388 The yeast homolog, Vps74p, interacts with and maintains the Golgi localization of several mannosyltransferases, which is subsequently critical for N- and O-glycosylation in yeast. 24733390 6 13 attach present 896:902 arg1 POMGnT1 926:932 POMGnT1 926:932 POMGnT1 926:932 In addition, we showed that three clinically relevant mutations present in the stem domain of POMGnT1 mislocalized to the endoplasmic reticulum, highlighting the importance of identifying the molecular mechanisms responsible for Golgi localization of glycosyltransferases. 24733390 6 13 attach present 896:902 arg1 domain 916:921 the stem domain 907:921 the stem domain of POMGnT1 907:932 In addition, we showed that three clinically relevant mutations present in the stem domain of POMGnT1 mislocalized to the endoplasmic reticulum, highlighting the importance of identifying the molecular mechanisms responsible for Golgi localization of glycosyltransferases. 24733390 6 13 attach present 896:902 arg2 mutations 886:894 three clinically relevant mutations 860:894 three clinically relevant mutations present in the stem domain of POMGnT1 860:932 In addition, we showed that three clinically relevant mutations present in the stem domain of POMGnT1 mislocalized to the endoplasmic reticulum, highlighting the importance of identifying the molecular mechanisms responsible for Golgi localization of glycosyltransferases. 24733390 5 14 theme functional 788:797 arg1 glycosylation 799:811 the functional glycosylation 784:811 the functional glycosylation of α-dystroglycan 784:829 Loss of this interaction resulted in the inability of POMGnT1 to localize to the Golgi and reduced the functional glycosylation of α-dystroglycan. 24733390 3 15 theme phage 415:419 arg1 display 421:427 a T7 phage display 410:427 a T7 phage display 410:427 Through the use of a T7 phage display, we discovered a novel interaction between GOLPH3 and a mammalian glycosyltransferase, POMGnT1, which is involved in the O-mannosylation of α-dystroglycan. 24733390 1 16 theme eukaryotic 191:200 arg1 lineage 202:208 the eukaryotic lineage 187:208 the eukaryotic lineage 187:208 GOLPH3 is a highly conserved protein found across the eukaryotic lineage. 24733390 6 17 theme relevant 877:884 arg1 mutations 886:894 three clinically relevant mutations 860:894 three clinically relevant mutations present in the stem domain of POMGnT1 860:932 In addition, we showed that three clinically relevant mutations present in the stem domain of POMGnT1 mislocalized to the endoplasmic reticulum, highlighting the importance of identifying the molecular mechanisms responsible for Golgi localization of glycosyltransferases. 24733390 2 18 from O-glycosylation 365:379 arg1 yeast 384:388 yeast 384:388 yeast 384:388 The yeast homolog, Vps74p, interacts with and maintains the Golgi localization of several mannosyltransferases, which is subsequently critical for N- and O-glycosylation in yeast. 24733390 3 19 theme α-dystroglycan 569:582 arg1 O-mannosylation 550:564 the O-mannosylation 546:564 the O-mannosylation of α-dystroglycan 546:582 Through the use of a T7 phage display, we discovered a novel interaction between GOLPH3 and a mammalian glycosyltransferase, POMGnT1, which is involved in the O-mannosylation of α-dystroglycan. 24733390 0 20 theme Golgi 0:4 arg1 phosphoprotein 6:19 Golgi phosphoprotein 3 0:21 Golgi phosphoprotein 3 0:21 Golgi phosphoprotein 3 mediates the Golgi localization and function of protein O-linked mannose β-1,2-N-acetlyglucosaminyltransferase 1. 24733390 6 21 theme glycosyltransferases 1083:1102 arg1 localization 1067:1078 Golgi localization 1061:1078 Golgi localization of glycosyltransferases 1061:1102 In addition, we showed that three clinically relevant mutations present in the stem domain of POMGnT1 mislocalized to the endoplasmic reticulum, highlighting the importance of identifying the molecular mechanisms responsible for Golgi localization of glycosyltransferases. 24733390 5 22 theme α-dystroglycan 816:829 arg1 glycosylation 799:811 the functional glycosylation 784:811 the functional glycosylation of α-dystroglycan 784:829 Loss of this interaction resulted in the inability of POMGnT1 to localize to the Golgi and reduced the functional glycosylation of α-dystroglycan. 24733390 5 23 theme interaction 698:708 arg1 Loss 685:688 Loss 685:688 Loss of this interaction 685:708 Loss of this interaction resulted in the inability of POMGnT1 to localize to the Golgi and reduced the functional glycosylation of α-dystroglycan. 24733390 0 24 theme Golgi 36:40 arg1 localization 42:53 Golgi localization 36:53 Golgi localization 36:53 Golgi phosphoprotein 3 mediates the Golgi localization and function of protein O-linked mannose β-1,2-N-acetlyglucosaminyltransferase 1. 24733390 6 25 theme endoplasmic 954:964 arg1 reticulum 966:974 the endoplasmic reticulum 950:974 the endoplasmic reticulum 950:974 In addition, we showed that three clinically relevant mutations present in the stem domain of POMGnT1 mislocalized to the endoplasmic reticulum, highlighting the importance of identifying the molecular mechanisms responsible for Golgi localization of glycosyltransferases. 24733390 2 26 gly O-glycosylation 365:379 arg1 yeast 384:388 yeast 384:388 yeast 384:388 The yeast homolog, Vps74p, interacts with and maintains the Golgi localization of several mannosyltransferases, which is subsequently critical for N- and O-glycosylation in yeast. 24733390 6 27 theme Golgi 1061:1065 arg1 localization 1067:1078 Golgi localization 1061:1078 Golgi localization of glycosyltransferases 1061:1102 In addition, we showed that three clinically relevant mutations present in the stem domain of POMGnT1 mislocalized to the endoplasmic reticulum, highlighting the importance of identifying the molecular mechanisms responsible for Golgi localization of glycosyltransferases. 24733390 3 28 theme novel 446:450 arg1 interaction 452:462 a novel interaction 444:462 a novel interaction between GOLPH3 and a mammalian glycosyltransferase, POMGnT1, which is involved in the O-mannosylation of α-dystroglycan 444:582 Through the use of a T7 phage display, we discovered a novel interaction between GOLPH3 and a mammalian glycosyltransferase, POMGnT1, which is involved in the O-mannosylation of α-dystroglycan. 24733390 3 29 theme display 421:427 arg1 use 403:405 the use 399:405 the use of a T7 phage display 399:427 Through the use of a T7 phage display, we discovered a novel interaction between GOLPH3 and a mammalian glycosyltransferase, POMGnT1, which is involved in the O-mannosylation of α-dystroglycan. 24733390 4 30 with interaction 660:670 arg1 GOLPH3 677:682 GOLPH3 677:682 GOLPH3 677:682 The cytoplasmic tail of POMGnT1 was found to be critical for mediating its interaction with GOLPH3. 24733390 0 31 dep localization 42:53 arg1 the 32:34 the 32:34 the 32:34 Golgi phosphoprotein 3 mediates the Golgi localization and function of protein O-linked mannose β-1,2-N-acetlyglucosaminyltransferase 1. 24733390 0 32 link O-linked 79:86 arg1 β-1,2-N-acetlyglucosaminyltransferase 96:132 protein O-linked mannose β-1,2-N-acetlyglucosaminyltransferase 1 71:134 protein O-linked mannose β-1,2-N-acetlyglucosaminyltransferase 1 71:134 Golgi phosphoprotein 3 mediates the Golgi localization and function of protein O-linked mannose β-1,2-N-acetlyglucosaminyltransferase 1. 24733390 6 33 from present 896:902 arg1 POMGnT1 926:932 POMGnT1 926:932 POMGnT1 926:932 In addition, we showed that three clinically relevant mutations present in the stem domain of POMGnT1 mislocalized to the endoplasmic reticulum, highlighting the importance of identifying the molecular mechanisms responsible for Golgi localization of glycosyltransferases. 24733390 6 33 from present 896:902 arg1 domain 916:921 the stem domain 907:921 the stem domain of POMGnT1 907:932 In addition, we showed that three clinically relevant mutations present in the stem domain of POMGnT1 mislocalized to the endoplasmic reticulum, highlighting the importance of identifying the molecular mechanisms responsible for Golgi localization of glycosyltransferases. 24733390 3 34 theme mammalian 485:493 arg1 POMGnT1 516:522 POMGnT1 516:522 POMGnT1 516:522 Through the use of a T7 phage display, we discovered a novel interaction between GOLPH3 and a mammalian glycosyltransferase, POMGnT1, which is involved in the O-mannosylation of α-dystroglycan. 24733390 3 34 theme mammalian 485:493 arg1 glycosyltransferase 495:513 a mammalian glycosyltransferase 483:513 a mammalian glycosyltransferase 483:513 Through the use of a T7 phage display, we discovered a novel interaction between GOLPH3 and a mammalian glycosyltransferase, POMGnT1, which is involved in the O-mannosylation of α-dystroglycan. 24733390 3 35 theme T7 412:413 arg1 display 421:427 a T7 phage display 410:427 a T7 phage display 410:427 Through the use of a T7 phage display, we discovered a novel interaction between GOLPH3 and a mammalian glycosyltransferase, POMGnT1, which is involved in the O-mannosylation of α-dystroglycan. 24733390 6 36 theme POMGnT1 926:932 arg1 POMGnT1 926:932 POMGnT1 926:932 POMGnT1 926:932 In addition, we showed that three clinically relevant mutations present in the stem domain of POMGnT1 mislocalized to the endoplasmic reticulum, highlighting the importance of identifying the molecular mechanisms responsible for Golgi localization of glycosyltransferases. 24733390 6 36 theme POMGnT1 926:932 arg1 domain 916:921 the stem domain 907:921 the stem domain of POMGnT1 907:932 In addition, we showed that three clinically relevant mutations present in the stem domain of POMGnT1 mislocalized to the endoplasmic reticulum, highlighting the importance of identifying the molecular mechanisms responsible for Golgi localization of glycosyltransferases. 24733390 7 37 theme Golgi 1166:1170 arg1 localization 1172:1183 the Golgi localization 1162:1183 the Golgi localization of POMGnT1 1162:1194 Our findings reveal a novel role for GOLPH3 in mediating the Golgi localization of POMGnT1. 24733390 2 38 theme Golgi 271:275 arg1 localization 277:288 the Golgi localization 267:288 the Golgi localization of several mannosyltransferases, which is subsequently critical for N- and O-glycosylation in yeast 267:388 The yeast homolog, Vps74p, interacts with and maintains the Golgi localization of several mannosyltransferases, which is subsequently critical for N- and O-glycosylation in yeast. 24733390 5 39 gly glycosylation 799:811 arg1 inability 726:734 the inability 722:734 the inability of POMGnT1 to localize to the Golgi 722:770 Loss of this interaction resulted in the inability of POMGnT1 to localize to the Golgi and reduced the functional glycosylation of α-dystroglycan. 24733390 5 39 gly glycosylation 799:811 arg1 α-dystroglycan 816:829 α-dystroglycan 816:829 α-dystroglycan 816:829 Loss of this interaction resulted in the inability of POMGnT1 to localize to the Golgi and reduced the functional glycosylation of α-dystroglycan. 24733390 6 40 theme responsible 1045:1055 arg1 mechanisms 1034:1043 the molecular mechanisms 1020:1043 the molecular mechanisms responsible for Golgi localization of glycosyltransferases 1020:1102 In addition, we showed that three clinically relevant mutations present in the stem domain of POMGnT1 mislocalized to the endoplasmic reticulum, highlighting the importance of identifying the molecular mechanisms responsible for Golgi localization of glycosyltransferases. 24733390 2 41 theme yeast 215:219 arg1 Vps74p 230:235 Vps74p 230:235 Vps74p 230:235 The yeast homolog, Vps74p, interacts with and maintains the Golgi localization of several mannosyltransferases, which is subsequently critical for N- and O-glycosylation in yeast. 24733390 2 41 theme yeast 215:219 arg1 homolog 221:227 The yeast homolog 211:227 The yeast homolog 211:227 The yeast homolog, Vps74p, interacts with and maintains the Golgi localization of several mannosyltransferases, which is subsequently critical for N- and O-glycosylation in yeast. 24733390 3 42 gly O-mannosylation 550:564 arg1 α-dystroglycan 569:582 α-dystroglycan 569:582 α-dystroglycan 569:582 Through the use of a T7 phage display, we discovered a novel interaction between GOLPH3 and a mammalian glycosyltransferase, POMGnT1, which is involved in the O-mannosylation of α-dystroglycan. 24733390 7 43 theme POMGnT1 1188:1194 arg1 localization 1172:1183 the Golgi localization 1162:1183 the Golgi localization of POMGnT1 1162:1194 Our findings reveal a novel role for GOLPH3 in mediating the Golgi localization of POMGnT1. 24733390 4 44 theme POMGnT1 609:615 arg1 tail 601:604 The cytoplasmic tail 585:604 The cytoplasmic tail of POMGnT1 585:615 The cytoplasmic tail of POMGnT1 was found to be critical for mediating its interaction with GOLPH3. 24733390 4 44 theme POMGnT1 609:615 arg1 critical 633:640 critical 633:640 critical 633:640 The cytoplasmic tail of POMGnT1 was found to be critical for mediating its interaction with GOLPH3. 24733390 1 45 theme conserved 156:164 arg1 protein 166:172 a highly conserved protein 147:172 a highly conserved protein found across the eukaryotic lineage 147:208 GOLPH3 is a highly conserved protein found across the eukaryotic lineage. 24733390 1 45 theme conserved 156:164 arg1 GOLPH3 137:142 GOLPH3 137:142 GOLPH3 137:142 GOLPH3 is a highly conserved protein found across the eukaryotic lineage. 24733390 6 46 theme molecular 1024:1032 arg1 mechanisms 1034:1043 the molecular mechanisms 1020:1043 the molecular mechanisms responsible for Golgi localization of glycosyltransferases 1020:1102 In addition, we showed that three clinically relevant mutations present in the stem domain of POMGnT1 mislocalized to the endoplasmic reticulum, highlighting the importance of identifying the molecular mechanisms responsible for Golgi localization of glycosyltransferases. 24706800 7 0 dep C. 1134:1135 arg1 elegans 1137:1143 C. elegans 1134:1143 C. elegans 1134:1143 With genetic approaches in D. melanogaster and C. elegans, we demonstrate the importance of high levels of this posttranslational modification for successful development at elevated temperatures. 24706800 7 1 theme high 1179:1182 arg1 levels 1184:1189 high levels 1179:1189 high levels of this posttranslational modification 1179:1228 With genetic approaches in D. melanogaster and C. elegans, we demonstrate the importance of high levels of this posttranslational modification for successful development at elevated temperatures. 24706800 6 2 theme O-GlcNAc 952:959 arg1 enzymes 943:949 the only two enzymes 930:949 the only two enzymes 930:949 Regulation seems to occur at the level of activity of the only two enzymes, O-GlcNAc transferase and O-GlcNAcase, that add and remove, respectively, this posttranslational modification in nucleus and cytoplasm. 24706800 6 2 theme O-GlcNAc 952:959 arg1 transferase 961:971 O-GlcNAc transferase 952:971 O-GlcNAc transferase 952:971 Regulation seems to occur at the level of activity of the only two enzymes, O-GlcNAc transferase and O-GlcNAcase, that add and remove, respectively, this posttranslational modification in nucleus and cytoplasm. 24706800 5 3 with modification 609:620 arg1 O-GlcNAc 656:663 O-GlcNAc 656:663 O-GlcNAc 656:663 Here we show that nucleocytoplasmic posttranslational modification of proteins with O-linked GlcNAc (O-GlcNAc) is closely correlated with ambient temperature during development of distantly related ectotherms ranging from the insect Drosophila melanogaster to the nematode Caenorhabditis elegans to the fish Danio rerio. 24706800 5 3 with modification 609:620 arg1 GlcNAc 648:653 O-linked GlcNAc 639:653 O-linked GlcNAc (O-GlcNAc) 639:664 Here we show that nucleocytoplasmic posttranslational modification of proteins with O-linked GlcNAc (O-GlcNAc) is closely correlated with ambient temperature during development of distantly related ectotherms ranging from the insect Drosophila melanogaster to the nematode Caenorhabditis elegans to the fish Danio rerio. 24706800 3 4 theme body 356:359 arg1 temperature 361:371 body temperature 356:371 body temperature 356:371 Hence thermal fluctuations pose a formidable challenge to ectothermic organisms in which body temperature is largely dictated by the ambient temperature. 24706800 7 5 theme levels 1184:1189 arg1 importance 1165:1174 the importance 1161:1174 the importance of high levels of this posttranslational modification for successful development at elevated temperatures 1161:1280 With genetic approaches in D. melanogaster and C. elegans, we demonstrate the importance of high levels of this posttranslational modification for successful development at elevated temperatures. 24706800 6 6 theme activity 918:925 arg1 level 909:913 the level 905:913 the level of activity of the only two enzymes, O-GlcNAc transferase and O-GlcNAcase, that add and remove, respectively, this posttranslational modification in nucleus and cytoplasm 905:1084 Regulation seems to occur at the level of activity of the only two enzymes, O-GlcNAc transferase and O-GlcNAcase, that add and remove, respectively, this posttranslational modification in nucleus and cytoplasm. 24706800 8 7 theme efficient 1448:1456 arg1 adjustment 1469:1478 an efficient coordinate adjustment 1445:1478 an efficient coordinate adjustment of cellular processes 1445:1500 Because many cytoplasmic and nuclear proteins in diverse pathways are O-GlcNAc targets, temperature-dependent regulation of this modification might contribute to an efficient coordinate adjustment of cellular processes in response to thermal change. 24706800 0 8 from resistance 54:63 arg1 development 78:88 ectotherm development 68:88 ectotherm development 68:88 O-GlcNAc reports ambient temperature and confers heat resistance on ectotherm development. 24706800 8 9 theme coordinate 1458:1467 arg1 adjustment 1469:1478 an efficient coordinate adjustment 1445:1478 an efficient coordinate adjustment of cellular processes 1445:1500 Because many cytoplasmic and nuclear proteins in diverse pathways are O-GlcNAc targets, temperature-dependent regulation of this modification might contribute to an efficient coordinate adjustment of cellular processes in response to thermal change. 24706800 6 10 theme posttranslational 1030:1046 arg1 modification 1048:1059 this posttranslational modification 1025:1059 this posttranslational modification 1025:1059 Regulation seems to occur at the level of activity of the only two enzymes, O-GlcNAc transferase and O-GlcNAcase, that add and remove, respectively, this posttranslational modification in nucleus and cytoplasm. 24706800 7 11 theme elevated 1260:1267 arg1 temperatures 1269:1280 elevated temperatures 1260:1280 elevated temperatures 1260:1280 With genetic approaches in D. melanogaster and C. elegans, we demonstrate the importance of high levels of this posttranslational modification for successful development at elevated temperatures. 24706800 3 12 theme thermal 273:279 arg1 fluctuations 281:292 Hence thermal fluctuations 267:292 Hence thermal fluctuations 267:292 Hence thermal fluctuations pose a formidable challenge to ectothermic organisms in which body temperature is largely dictated by the ambient temperature. 24706800 5 13 theme nematode 819:826 arg1 elegans 843:849 the nematode Caenorhabditis elegans 815:849 the nematode Caenorhabditis elegans 815:849 Here we show that nucleocytoplasmic posttranslational modification of proteins with O-linked GlcNAc (O-GlcNAc) is closely correlated with ambient temperature during development of distantly related ectotherms ranging from the insect Drosophila melanogaster to the nematode Caenorhabditis elegans to the fish Danio rerio. 24706800 6 14 theme enzymes 943:949 arg1 activity 918:925 activity 918:925 activity of the only two enzymes, O-GlcNAc transferase and O-GlcNAcase, that add and remove, respectively, this posttranslational modification in nucleus and cytoplasm 918:1084 Regulation seems to occur at the level of activity of the only two enzymes, O-GlcNAc transferase and O-GlcNAcase, that add and remove, respectively, this posttranslational modification in nucleus and cytoplasm. 24706800 7 15 theme posttranslational 1199:1215 arg1 modification 1217:1228 this posttranslational modification 1194:1228 this posttranslational modification 1194:1228 With genetic approaches in D. melanogaster and C. elegans, we demonstrate the importance of high levels of this posttranslational modification for successful development at elevated temperatures. 24706800 5 16 theme proteins 625:632 arg1 modification 609:620 nucleocytoplasmic posttranslational modification 573:620 nucleocytoplasmic posttranslational modification of proteins with O-linked GlcNAc (O-GlcNAc) 573:664 Here we show that nucleocytoplasmic posttranslational modification of proteins with O-linked GlcNAc (O-GlcNAc) is closely correlated with ambient temperature during development of distantly related ectotherms ranging from the insect Drosophila melanogaster to the nematode Caenorhabditis elegans to the fish Danio rerio. 24706800 4 17 from cells 425:429 arg1 ectotherms 434:443 ectotherms 434:443 ectotherms 434:443 How cells in ectotherms cope with the myriad disruptive effects of temperature variation is poorly understood at the molecular level. 24706800 7 18 theme genetic 1092:1098 arg1 approaches 1100:1109 genetic approaches 1092:1109 genetic approaches in D. melanogaster and C. elegans 1092:1143 With genetic approaches in D. melanogaster and C. elegans, we demonstrate the importance of high levels of this posttranslational modification for successful development at elevated temperatures. 24706800 5 19 theme Caenorhabditis 828:841 arg1 elegans 843:849 the nematode Caenorhabditis elegans 815:849 the nematode Caenorhabditis elegans 815:849 Here we show that nucleocytoplasmic posttranslational modification of proteins with O-linked GlcNAc (O-GlcNAc) is closely correlated with ambient temperature during development of distantly related ectotherms ranging from the insect Drosophila melanogaster to the nematode Caenorhabditis elegans to the fish Danio rerio. 24706800 8 20 theme cellular 1483:1490 arg1 processes 1492:1500 cellular processes 1483:1500 cellular processes 1483:1500 Because many cytoplasmic and nuclear proteins in diverse pathways are O-GlcNAc targets, temperature-dependent regulation of this modification might contribute to an efficient coordinate adjustment of cellular processes in response to thermal change. 24706800 2 21 theme enzymatic 195:203 arg1 reactions 205:213 the diverse enzymatic reactions 183:213 the diverse enzymatic reactions that have distinct individual temperature profiles 183:264 Diffusion is less affected than the diverse enzymatic reactions that have distinct individual temperature profiles. 24706800 5 22 theme O-linked 639:646 arg1 O-GlcNAc 656:663 O-GlcNAc 656:663 O-GlcNAc 656:663 Here we show that nucleocytoplasmic posttranslational modification of proteins with O-linked GlcNAc (O-GlcNAc) is closely correlated with ambient temperature during development of distantly related ectotherms ranging from the insect Drosophila melanogaster to the nematode Caenorhabditis elegans to the fish Danio rerio. 24706800 5 22 theme O-linked 639:646 arg1 GlcNAc 648:653 O-linked GlcNAc 639:653 O-linked GlcNAc (O-GlcNAc) 639:664 Here we show that nucleocytoplasmic posttranslational modification of proteins with O-linked GlcNAc (O-GlcNAc) is closely correlated with ambient temperature during development of distantly related ectotherms ranging from the insect Drosophila melanogaster to the nematode Caenorhabditis elegans to the fish Danio rerio. 24706800 8 23 theme diverse 1332:1338 arg1 pathways 1340:1347 diverse pathways 1332:1347 diverse pathways 1332:1347 Because many cytoplasmic and nuclear proteins in diverse pathways are O-GlcNAc targets, temperature-dependent regulation of this modification might contribute to an efficient coordinate adjustment of cellular processes in response to thermal change. 24706800 3 24 theme ambient 400:406 arg1 temperature 408:418 the ambient temperature 396:418 the ambient temperature 396:418 Hence thermal fluctuations pose a formidable challenge to ectothermic organisms in which body temperature is largely dictated by the ambient temperature. 24706800 3 25 theme formidable 301:310 arg1 challenge 312:320 a formidable challenge 299:320 a formidable challenge to ectothermic organisms in which body temperature is largely dictated by the ambient temperature 299:418 Hence thermal fluctuations pose a formidable challenge to ectothermic organisms in which body temperature is largely dictated by the ambient temperature. 24706800 8 26 theme thermal 1517:1523 arg1 change 1525:1530 thermal change 1517:1530 thermal change 1517:1530 Because many cytoplasmic and nuclear proteins in diverse pathways are O-GlcNAc targets, temperature-dependent regulation of this modification might contribute to an efficient coordinate adjustment of cellular processes in response to thermal change. 24706800 1 27 theme temperature 102:112 arg1 Effects 91:97 Effects 91:97 Effects of temperature on biological processes 91:136 Effects of temperature on biological processes are complex. 24706800 7 28 dep D. 1114:1115 arg1 melanogaster 1117:1128 D. melanogaster 1114:1128 D. melanogaster 1114:1128 With genetic approaches in D. melanogaster and C. elegans, we demonstrate the importance of high levels of this posttranslational modification for successful development at elevated temperatures. 24706800 0 29 theme ambient 17:23 arg1 temperature 25:35 ambient temperature 17:35 ambient temperature 17:35 O-GlcNAc reports ambient temperature and confers heat resistance on ectotherm development. 24706800 2 30 theme diverse 187:193 arg1 reactions 205:213 the diverse enzymatic reactions 183:213 the diverse enzymatic reactions that have distinct individual temperature profiles 183:264 Diffusion is less affected than the diverse enzymatic reactions that have distinct individual temperature profiles. 24706800 8 31 theme processes 1492:1500 arg1 adjustment 1469:1478 an efficient coordinate adjustment 1445:1478 an efficient coordinate adjustment of cellular processes 1445:1500 Because many cytoplasmic and nuclear proteins in diverse pathways are O-GlcNAc targets, temperature-dependent regulation of this modification might contribute to an efficient coordinate adjustment of cellular processes in response to thermal change. 24706800 5 32 theme fish 858:861 arg1 rerio 869:873 the fish Danio rerio 854:873 the fish Danio rerio 854:873 Here we show that nucleocytoplasmic posttranslational modification of proteins with O-linked GlcNAc (O-GlcNAc) is closely correlated with ambient temperature during development of distantly related ectotherms ranging from the insect Drosophila melanogaster to the nematode Caenorhabditis elegans to the fish Danio rerio. 24706800 8 33 theme temperature-dependent 1371:1391 arg1 regulation 1393:1402 temperature-dependent regulation 1371:1402 temperature-dependent regulation of this modification 1371:1423 Because many cytoplasmic and nuclear proteins in diverse pathways are O-GlcNAc targets, temperature-dependent regulation of this modification might contribute to an efficient coordinate adjustment of cellular processes in response to thermal change. 24706800 7 34 from temperatures 1269:1280 arg1 development 1245:1255 successful development 1234:1255 successful development at elevated temperatures 1234:1280 With genetic approaches in D. melanogaster and C. elegans, we demonstrate the importance of high levels of this posttranslational modification for successful development at elevated temperatures. 24706800 5 35 theme Danio 863:867 arg1 rerio 869:873 the fish Danio rerio 854:873 the fish Danio rerio 854:873 Here we show that nucleocytoplasmic posttranslational modification of proteins with O-linked GlcNAc (O-GlcNAc) is closely correlated with ambient temperature during development of distantly related ectotherms ranging from the insect Drosophila melanogaster to the nematode Caenorhabditis elegans to the fish Danio rerio. 24706800 7 36 theme modification 1217:1228 arg1 levels 1184:1189 high levels 1179:1189 high levels of this posttranslational modification 1179:1228 With genetic approaches in D. melanogaster and C. elegans, we demonstrate the importance of high levels of this posttranslational modification for successful development at elevated temperatures. 24706800 4 37 theme variation 500:508 arg1 effects 477:483 the myriad disruptive effects 455:483 the myriad disruptive effects of temperature variation 455:508 How cells in ectotherms cope with the myriad disruptive effects of temperature variation is poorly understood at the molecular level. 24706800 2 38 theme temperature 245:255 arg1 profiles 257:264 distinct individual temperature profiles 225:264 distinct individual temperature profiles 225:264 Diffusion is less affected than the diverse enzymatic reactions that have distinct individual temperature profiles. 24706800 5 39 theme nucleocytoplasmic 573:589 arg1 modification 609:620 nucleocytoplasmic posttranslational modification 573:620 nucleocytoplasmic posttranslational modification of proteins with O-linked GlcNAc (O-GlcNAc) 573:664 Here we show that nucleocytoplasmic posttranslational modification of proteins with O-linked GlcNAc (O-GlcNAc) is closely correlated with ambient temperature during development of distantly related ectotherms ranging from the insect Drosophila melanogaster to the nematode Caenorhabditis elegans to the fish Danio rerio. 24706800 2 40 contain have 220:223 arg1 reactions 205:213 the diverse enzymatic reactions 183:213 the diverse enzymatic reactions that have distinct individual temperature profiles 183:264 Diffusion is less affected than the diverse enzymatic reactions that have distinct individual temperature profiles. 24706800 2 40 contain have 220:223 arg2 profiles 257:264 distinct individual temperature profiles 225:264 distinct individual temperature profiles 225:264 Diffusion is less affected than the diverse enzymatic reactions that have distinct individual temperature profiles. 24706800 8 41 theme nuclear 1312:1318 arg1 proteins 1320:1327 many cytoplasmic and nuclear proteins 1291:1327 many cytoplasmic and nuclear proteins in diverse pathways 1291:1347 Because many cytoplasmic and nuclear proteins in diverse pathways are O-GlcNAc targets, temperature-dependent regulation of this modification might contribute to an efficient coordinate adjustment of cellular processes in response to thermal change. 24706800 8 41 theme nuclear 1312:1318 arg1 targets 1362:1368 O-GlcNAc targets 1353:1368 O-GlcNAc targets 1353:1368 Because many cytoplasmic and nuclear proteins in diverse pathways are O-GlcNAc targets, temperature-dependent regulation of this modification might contribute to an efficient coordinate adjustment of cellular processes in response to thermal change. 24706800 8 42 theme many 1291:1294 arg1 proteins 1320:1327 many cytoplasmic and nuclear proteins 1291:1327 many cytoplasmic and nuclear proteins in diverse pathways 1291:1347 Because many cytoplasmic and nuclear proteins in diverse pathways are O-GlcNAc targets, temperature-dependent regulation of this modification might contribute to an efficient coordinate adjustment of cellular processes in response to thermal change. 24706800 8 42 theme many 1291:1294 arg1 targets 1362:1368 O-GlcNAc targets 1353:1368 O-GlcNAc targets 1353:1368 Because many cytoplasmic and nuclear proteins in diverse pathways are O-GlcNAc targets, temperature-dependent regulation of this modification might contribute to an efficient coordinate adjustment of cellular processes in response to thermal change. 24706800 4 43 theme temperature 488:498 arg1 variation 500:508 temperature variation 488:508 temperature variation 488:508 How cells in ectotherms cope with the myriad disruptive effects of temperature variation is poorly understood at the molecular level. 24706800 2 44 theme individual 234:243 arg1 profiles 257:264 distinct individual temperature profiles 225:264 distinct individual temperature profiles 225:264 Diffusion is less affected than the diverse enzymatic reactions that have distinct individual temperature profiles. 24706800 5 45 theme posttranslational 591:607 arg1 modification 609:620 nucleocytoplasmic posttranslational modification 573:620 nucleocytoplasmic posttranslational modification of proteins with O-linked GlcNAc (O-GlcNAc) 573:664 Here we show that nucleocytoplasmic posttranslational modification of proteins with O-linked GlcNAc (O-GlcNAc) is closely correlated with ambient temperature during development of distantly related ectotherms ranging from the insect Drosophila melanogaster to the nematode Caenorhabditis elegans to the fish Danio rerio. 24706800 1 46 theme biological 117:126 arg1 processes 128:136 biological processes 117:136 biological processes 117:136 Effects of temperature on biological processes are complex. 24706800 0 47 theme heat 49:52 arg1 resistance 54:63 heat resistance 49:63 heat resistance on ectotherm development 49:88 O-GlcNAc reports ambient temperature and confers heat resistance on ectotherm development. 24706800 5 48 theme related 745:751 arg1 ectotherms 753:762 distantly related ectotherms 735:762 distantly related ectotherms ranging from the insect Drosophila melanogaster to the nematode Caenorhabditis elegans to the fish Danio rerio 735:873 Here we show that nucleocytoplasmic posttranslational modification of proteins with O-linked GlcNAc (O-GlcNAc) is closely correlated with ambient temperature during development of distantly related ectotherms ranging from the insect Drosophila melanogaster to the nematode Caenorhabditis elegans to the fish Danio rerio. 24706800 2 49 theme distinct 225:232 arg1 profiles 257:264 distinct individual temperature profiles 225:264 distinct individual temperature profiles 225:264 Diffusion is less affected than the diverse enzymatic reactions that have distinct individual temperature profiles. 24706800 5 50 theme ambient 693:699 arg1 temperature 701:711 ambient temperature 693:711 ambient temperature during development of distantly related ectotherms ranging from the insect Drosophila melanogaster to the nematode Caenorhabditis elegans to the fish Danio rerio 693:873 Here we show that nucleocytoplasmic posttranslational modification of proteins with O-linked GlcNAc (O-GlcNAc) is closely correlated with ambient temperature during development of distantly related ectotherms ranging from the insect Drosophila melanogaster to the nematode Caenorhabditis elegans to the fish Danio rerio. 24706800 5 51 theme ectotherms 753:762 arg1 development 720:730 development 720:730 development of distantly related ectotherms ranging from the insect Drosophila melanogaster to the nematode Caenorhabditis elegans to the fish Danio rerio 720:873 Here we show that nucleocytoplasmic posttranslational modification of proteins with O-linked GlcNAc (O-GlcNAc) is closely correlated with ambient temperature during development of distantly related ectotherms ranging from the insect Drosophila melanogaster to the nematode Caenorhabditis elegans to the fish Danio rerio. 24706800 8 52 from proteins 1320:1327 arg1 pathways 1340:1347 diverse pathways 1332:1347 diverse pathways 1332:1347 Because many cytoplasmic and nuclear proteins in diverse pathways are O-GlcNAc targets, temperature-dependent regulation of this modification might contribute to an efficient coordinate adjustment of cellular processes in response to thermal change. 24706800 5 53 link O-linked 639:646 arg1 O-GlcNAc 656:663 O-GlcNAc 656:663 O-GlcNAc 656:663 Here we show that nucleocytoplasmic posttranslational modification of proteins with O-linked GlcNAc (O-GlcNAc) is closely correlated with ambient temperature during development of distantly related ectotherms ranging from the insect Drosophila melanogaster to the nematode Caenorhabditis elegans to the fish Danio rerio. 24706800 5 53 link O-linked 639:646 arg1 GlcNAc 648:653 O-linked GlcNAc 639:653 O-linked GlcNAc (O-GlcNAc) 639:664 Here we show that nucleocytoplasmic posttranslational modification of proteins with O-linked GlcNAc (O-GlcNAc) is closely correlated with ambient temperature during development of distantly related ectotherms ranging from the insect Drosophila melanogaster to the nematode Caenorhabditis elegans to the fish Danio rerio. 24706800 3 54 theme ectothermic 325:335 arg1 organisms 337:345 ectothermic organisms 325:345 ectothermic organisms in which body temperature is largely dictated by the ambient temperature 325:418 Hence thermal fluctuations pose a formidable challenge to ectothermic organisms in which body temperature is largely dictated by the ambient temperature. 24706800 4 55 theme disruptive 466:475 arg1 effects 477:483 the myriad disruptive effects 455:483 the myriad disruptive effects of temperature variation 455:508 How cells in ectotherms cope with the myriad disruptive effects of temperature variation is poorly understood at the molecular level. 24706800 8 56 theme cytoplasmic 1296:1306 arg1 proteins 1320:1327 many cytoplasmic and nuclear proteins 1291:1327 many cytoplasmic and nuclear proteins in diverse pathways 1291:1347 Because many cytoplasmic and nuclear proteins in diverse pathways are O-GlcNAc targets, temperature-dependent regulation of this modification might contribute to an efficient coordinate adjustment of cellular processes in response to thermal change. 24706800 8 56 theme cytoplasmic 1296:1306 arg1 targets 1362:1368 O-GlcNAc targets 1353:1368 O-GlcNAc targets 1353:1368 Because many cytoplasmic and nuclear proteins in diverse pathways are O-GlcNAc targets, temperature-dependent regulation of this modification might contribute to an efficient coordinate adjustment of cellular processes in response to thermal change. 24706800 1 57 from Effects 91:97 arg1 processes 128:136 biological processes 117:136 biological processes 117:136 Effects of temperature on biological processes are complex. 24706800 7 58 from approaches 1100:1109 arg1 D. 1114:1115 D. 1114:1115 D. 1114:1115 With genetic approaches in D. melanogaster and C. elegans, we demonstrate the importance of high levels of this posttranslational modification for successful development at elevated temperatures. 24706800 7 58 from approaches 1100:1109 arg1 C. 1134:1135 C. 1134:1135 C. 1134:1135 With genetic approaches in D. melanogaster and C. elegans, we demonstrate the importance of high levels of this posttranslational modification for successful development at elevated temperatures. 24706800 0 59 theme ectotherm 68:76 arg1 development 78:88 ectotherm development 68:88 ectotherm development 68:88 O-GlcNAc reports ambient temperature and confers heat resistance on ectotherm development. 24706800 4 60 theme myriad 459:464 arg1 effects 477:483 the myriad disruptive effects 455:483 the myriad disruptive effects of temperature variation 455:508 How cells in ectotherms cope with the myriad disruptive effects of temperature variation is poorly understood at the molecular level. 24706800 8 61 theme O-GlcNAc 1353:1360 arg1 proteins 1320:1327 many cytoplasmic and nuclear proteins 1291:1327 many cytoplasmic and nuclear proteins in diverse pathways 1291:1347 Because many cytoplasmic and nuclear proteins in diverse pathways are O-GlcNAc targets, temperature-dependent regulation of this modification might contribute to an efficient coordinate adjustment of cellular processes in response to thermal change. 24706800 8 61 theme O-GlcNAc 1353:1360 arg1 targets 1362:1368 O-GlcNAc targets 1353:1368 O-GlcNAc targets 1353:1368 Because many cytoplasmic and nuclear proteins in diverse pathways are O-GlcNAc targets, temperature-dependent regulation of this modification might contribute to an efficient coordinate adjustment of cellular processes in response to thermal change. 24706800 4 62 theme molecular 538:546 arg1 level 548:552 the molecular level 534:552 the molecular level 534:552 How cells in ectotherms cope with the myriad disruptive effects of temperature variation is poorly understood at the molecular level. 24706800 7 63 theme successful 1234:1243 arg1 development 1245:1255 successful development 1234:1255 successful development at elevated temperatures 1234:1280 With genetic approaches in D. melanogaster and C. elegans, we demonstrate the importance of high levels of this posttranslational modification for successful development at elevated temperatures. 24706800 8 64 theme modification 1412:1423 arg1 regulation 1393:1402 temperature-dependent regulation 1371:1402 temperature-dependent regulation of this modification 1371:1423 Because many cytoplasmic and nuclear proteins in diverse pathways are O-GlcNAc targets, temperature-dependent regulation of this modification might contribute to an efficient coordinate adjustment of cellular processes in response to thermal change. 24517196 3 0 theme thyroglobulin 532:544 arg1 glycans 514:520 the terminal α-galactose (TAG)-containing glycans 472:520 the terminal α-galactose (TAG)-containing glycans of bovine thyroglobulin 472:544 Recognition of either the terminal α-galactose (TAG)-containing glycans of bovine thyroglobulin or the N-acetyl lactosamine (LacNAc)-terminating glycans of asialofetuin by LIg was inhibitable nearly as much by the α-galactoside melibiose as by the β-galactoside lactose. 24517196 3 0 theme thyroglobulin 532:544 arg1 glycans 595:601 the N-acetyl lactosamine (LacNAc)-terminating glycans 549:601 the N-acetyl lactosamine (LacNAc)-terminating glycans of asialofetuin 549:617 Recognition of either the terminal α-galactose (TAG)-containing glycans of bovine thyroglobulin or the N-acetyl lactosamine (LacNAc)-terminating glycans of asialofetuin by LIg was inhibitable nearly as much by the α-galactoside melibiose as by the β-galactoside lactose. 24517196 9 1 theme neuraminidase 1786:1798 arg1 release 1775:1781 greater release 1767:1781 greater release of neuraminidase into circulation 1767:1815 Results suggest (1) possibility of a role for LIg in combating non-primate molecules and cells bearing TAG moiety and (2) a mechanism for Lp(a)-mediated vascular injury as diabetes, infections and inflammations induce greater release of neuraminidase into circulation. 24517196 8 2 with complex 1483:1489 arg1 a 1499:1499 a 1499:1499 a 1499:1499 Further, same amount of added fluorescence-labelled LIg formed significantly more immune complex with Lp(a) in high Lp(a) plasma than in low Lp(a) plasma. 24517196 8 2 with complex 1483:1489 arg1 Lp 1496:1497 Lp 1496:1497 Lp(a) in high Lp(a) plasma 1496:1521 Further, same amount of added fluorescence-labelled LIg formed significantly more immune complex with Lp(a) in high Lp(a) plasma than in low Lp(a) plasma. 24517196 1 3 theme lactose-binding 179:193 arg1 immunoglobulin 195:208 Human plasma lactose-binding immunoglobulin 166:208 Human plasma lactose-binding immunoglobulin (LIg) isolated by affinity chromatography on lactose-Sepharose 166:271 Human plasma lactose-binding immunoglobulin (LIg) isolated by affinity chromatography on lactose-Sepharose was largely IgG with significant IgA and IgM contents. 24517196 1 3 theme lactose-binding 179:193 arg1 LIg 211:213 LIg 211:213 LIg 211:213 Human plasma lactose-binding immunoglobulin (LIg) isolated by affinity chromatography on lactose-Sepharose was largely IgG with significant IgA and IgM contents. 24517196 2 4 theme LIg-mediated 328:339 arg1 agglutination 341:353 LIg-mediated agglutination 328:353 LIg-mediated agglutination of desialylated human RBC 328:379 LIg-mediated agglutination of desialylated human RBC was inhibited equally by the α- and β-anomers of methyl galactoside. 24517196 5 5 theme membrane 915:922 arg1 both 934:937 both 934:937 both 934:937 LIg binding to bovine thyroglobulin or rabbit RBC membrane proteins, both bearing TAG was substantially reduced by prior treatment of the proteins with α-galactosidase to remove TAG though enzyme-treated glycans contained newly exposed LacNAc moieties. 24517196 5 5 theme membrane 915:922 arg1 proteins 924:931 bovine thyroglobulin or rabbit RBC membrane proteins 880:931 bovine thyroglobulin or rabbit RBC membrane proteins 880:931 LIg binding to bovine thyroglobulin or rabbit RBC membrane proteins, both bearing TAG was substantially reduced by prior treatment of the proteins with α-galactosidase to remove TAG though enzyme-treated glycans contained newly exposed LacNAc moieties. 24517196 9 6 theme non-primate 1612:1622 arg1 inflammations 1746:1758 inflammations 1746:1758 inflammations 1746:1758 Results suggest (1) possibility of a role for LIg in combating non-primate molecules and cells bearing TAG moiety and (2) a mechanism for Lp(a)-mediated vascular injury as diabetes, infections and inflammations induce greater release of neuraminidase into circulation. 24517196 9 6 theme non-primate 1612:1622 arg1 infections 1731:1740 infections 1731:1740 infections 1731:1740 Results suggest (1) possibility of a role for LIg in combating non-primate molecules and cells bearing TAG moiety and (2) a mechanism for Lp(a)-mediated vascular injury as diabetes, infections and inflammations induce greater release of neuraminidase into circulation. 24517196 9 6 theme non-primate 1612:1622 arg1 cells 1638:1642 cells 1638:1642 cells 1638:1642 Results suggest (1) possibility of a role for LIg in combating non-primate molecules and cells bearing TAG moiety and (2) a mechanism for Lp(a)-mediated vascular injury as diabetes, infections and inflammations induce greater release of neuraminidase into circulation. 24517196 9 6 theme non-primate 1612:1622 arg1 diabetes 1721:1728 diabetes 1721:1728 diabetes 1721:1728 Results suggest (1) possibility of a role for LIg in combating non-primate molecules and cells bearing TAG moiety and (2) a mechanism for Lp(a)-mediated vascular injury as diabetes, infections and inflammations induce greater release of neuraminidase into circulation. 24517196 9 6 theme non-primate 1612:1622 arg1 molecules 1624:1632 non-primate molecules 1612:1632 non-primate molecules 1612:1632 Results suggest (1) possibility of a role for LIg in combating non-primate molecules and cells bearing TAG moiety and (2) a mechanism for Lp(a)-mediated vascular injury as diabetes, infections and inflammations induce greater release of neuraminidase into circulation. 24517196 0 7 theme lipoprotein 133:143 arg1 recognition 105:115 recognition 105:115 recognition of desialylated lipoprotein(a) and xenoantigens 105:163 Dual specificity of human plasma lactose-binding immunoglobulin to anomers of terminal galactose enables recognition of desialylated lipoprotein(a) and xenoantigens. 24517196 3 8 theme -terminating 582:593 arg1 glycans 595:601 the N-acetyl lactosamine (LacNAc)-terminating glycans 549:601 the N-acetyl lactosamine (LacNAc)-terminating glycans of asialofetuin 549:617 Recognition of either the terminal α-galactose (TAG)-containing glycans of bovine thyroglobulin or the N-acetyl lactosamine (LacNAc)-terminating glycans of asialofetuin by LIg was inhibitable nearly as much by the α-galactoside melibiose as by the β-galactoside lactose. 24517196 8 9 theme LIg 1446:1448 arg1 LIg 1446:1448 added fluorescence-labelled LIg 1418:1448 added fluorescence-labelled LIg 1418:1448 Further, same amount of added fluorescence-labelled LIg formed significantly more immune complex with Lp(a) in high Lp(a) plasma than in low Lp(a) plasma. 24517196 8 9 theme LIg 1446:1448 arg1 amount 1408:1413 same amount 1403:1413 same amount of added fluorescence-labelled LIg 1403:1448 Further, same amount of added fluorescence-labelled LIg formed significantly more immune complex with Lp(a) in high Lp(a) plasma than in low Lp(a) plasma. 24517196 9 10 dep suggest 1557:1563 arg1 induce 1760:1765 induce 1760:1765 suggest (1) possibility of a role for LIg in combating non-primate molecules and cells bearing TAG moiety and (2) a mechanism for Lp(a)-mediated vascular injury as diabetes, infections and inflammations induce greater release of neuraminidase into circulation 1557:1815 Results suggest (1) possibility of a role for LIg in combating non-primate molecules and cells bearing TAG moiety and (2) a mechanism for Lp(a)-mediated vascular injury as diabetes, infections and inflammations induce greater release of neuraminidase into circulation. 24517196 7 11 theme lipoprotein 1210:1220 arg1 a 1229:1229 a 1229:1229 a 1229:1229 Unlike LDL, plasma lipoprotein(a) [Lp(a)] coated on polystyrene well and desialylated by neuraminidase was recognized by LIg through terminal LacNAc moieties exposed by the enzyme on its apo(a) subunit. 24517196 7 11 theme lipoprotein 1210:1220 arg1 [Lp 1225:1227 plasma lipoprotein(a) [Lp 1203:1227 plasma lipoprotein(a) [Lp(a)] coated on polystyrene well and desialylated by neuraminidase 1203:1292 Unlike LDL, plasma lipoprotein(a) [Lp(a)] coated on polystyrene well and desialylated by neuraminidase was recognized by LIg through terminal LacNAc moieties exposed by the enzyme on its apo(a) subunit. 24517196 5 12 theme thyroglobulin 887:899 arg1 both 934:937 both 934:937 both 934:937 LIg binding to bovine thyroglobulin or rabbit RBC membrane proteins, both bearing TAG was substantially reduced by prior treatment of the proteins with α-galactosidase to remove TAG though enzyme-treated glycans contained newly exposed LacNAc moieties. 24517196 5 12 theme thyroglobulin 887:899 arg1 proteins 924:931 bovine thyroglobulin or rabbit RBC membrane proteins 880:931 bovine thyroglobulin or rabbit RBC membrane proteins 880:931 LIg binding to bovine thyroglobulin or rabbit RBC membrane proteins, both bearing TAG was substantially reduced by prior treatment of the proteins with α-galactosidase to remove TAG though enzyme-treated glycans contained newly exposed LacNAc moieties. 24517196 5 13 theme exposed 1093:1099 arg1 moieties 1108:1115 newly exposed LacNAc moieties 1087:1115 newly exposed LacNAc moieties 1087:1115 LIg binding to bovine thyroglobulin or rabbit RBC membrane proteins, both bearing TAG was substantially reduced by prior treatment of the proteins with α-galactosidase to remove TAG though enzyme-treated glycans contained newly exposed LacNAc moieties. 24517196 8 14 theme immune 1476:1481 arg1 complex 1483:1489 significantly more immune complex 1457:1489 significantly more immune complex with Lp(a) in high Lp(a) plasma 1457:1521 Further, same amount of added fluorescence-labelled LIg formed significantly more immune complex with Lp(a) in high Lp(a) plasma than in low Lp(a) plasma. 24517196 1 15 from chromatography 237:250 arg1 lactose-Sepharose 255:271 lactose-Sepharose 255:271 lactose-Sepharose 255:271 Human plasma lactose-binding immunoglobulin (LIg) isolated by affinity chromatography on lactose-Sepharose was largely IgG with significant IgA and IgM contents. 24517196 7 16 theme polystyrene 1243:1253 arg1 well 1255:1258 polystyrene well 1243:1258 polystyrene well 1243:1258 Unlike LDL, plasma lipoprotein(a) [Lp(a)] coated on polystyrene well and desialylated by neuraminidase was recognized by LIg through terminal LacNAc moieties exposed by the enzyme on its apo(a) subunit. 24517196 0 17 theme terminal 78:85 arg1 galactose 87:95 terminal galactose 78:95 terminal galactose 78:95 Dual specificity of human plasma lactose-binding immunoglobulin to anomers of terminal galactose enables recognition of desialylated lipoprotein(a) and xenoantigens. 24517196 1 18 theme Human 166:170 arg1 immunoglobulin 195:208 Human plasma lactose-binding immunoglobulin 166:208 Human plasma lactose-binding immunoglobulin (LIg) isolated by affinity chromatography on lactose-Sepharose 166:271 Human plasma lactose-binding immunoglobulin (LIg) isolated by affinity chromatography on lactose-Sepharose was largely IgG with significant IgA and IgM contents. 24517196 1 18 theme Human 166:170 arg1 LIg 211:213 LIg 211:213 LIg 211:213 Human plasma lactose-binding immunoglobulin (LIg) isolated by affinity chromatography on lactose-Sepharose was largely IgG with significant IgA and IgM contents. 24517196 4 19 theme several 805:811 arg1 times 813:817 several times 805:817 several times more LIg molecules than its lactose analogue 805:862 Melibiose covalently conjugated to protein and coated on polystyrene wells captured several times more LIg molecules than its lactose analogue. 24517196 5 20 theme proteins 1003:1010 arg1 treatment 986:994 prior treatment 980:994 prior treatment of the proteins with α-galactosidase 980:1031 LIg binding to bovine thyroglobulin or rabbit RBC membrane proteins, both bearing TAG was substantially reduced by prior treatment of the proteins with α-galactosidase to remove TAG though enzyme-treated glycans contained newly exposed LacNAc moieties. 24517196 8 21 theme high 1505:1508 arg1 Lp 1510:1511 high Lp 1505:1511 high Lp(a) plasma 1505:1521 Further, same amount of added fluorescence-labelled LIg formed significantly more immune complex with Lp(a) in high Lp(a) plasma than in low Lp(a) plasma. 24517196 8 21 theme high 1505:1508 arg1 a 1513:1513 a 1513:1513 a 1513:1513 Further, same amount of added fluorescence-labelled LIg formed significantly more immune complex with Lp(a) in high Lp(a) plasma than in low Lp(a) plasma. 24517196 4 22 theme more 819:822 arg1 times 813:817 several times 805:817 several times more LIg molecules than its lactose analogue 805:862 Melibiose covalently conjugated to protein and coated on polystyrene wells captured several times more LIg molecules than its lactose analogue. 24517196 0 23 theme Dual 0:3 arg1 specificity 5:15 Dual specificity 0:15 Dual specificity of human plasma lactose-binding immunoglobulin to anomers of terminal galactose 0:95 Dual specificity of human plasma lactose-binding immunoglobulin to anomers of terminal galactose enables recognition of desialylated lipoprotein(a) and xenoantigens. 24517196 1 24 theme significant 294:304 arg1 contents 318:325 significant IgA and IgM contents 294:325 significant IgA and IgM contents 294:325 Human plasma lactose-binding immunoglobulin (LIg) isolated by affinity chromatography on lactose-Sepharose was largely IgG with significant IgA and IgM contents. 24517196 5 25 theme prior 980:984 arg1 treatment 986:994 prior treatment 980:994 prior treatment of the proteins with α-galactosidase 980:1031 LIg binding to bovine thyroglobulin or rabbit RBC membrane proteins, both bearing TAG was substantially reduced by prior treatment of the proteins with α-galactosidase to remove TAG though enzyme-treated glycans contained newly exposed LacNAc moieties. 24517196 6 26 theme Desialylated 1118:1129 arg1 oligosaccharides 1140:1155 Desialylated O-linked oligosaccharides 1118:1155 Desialylated O-linked oligosaccharides 1118:1155 Desialylated O-linked oligosaccharides, however, were no ligand for LIg. 24517196 9 27 theme -mediated 1692:1700 arg1 injury 1711:1716 Lp(a)-mediated vascular injury 1687:1716 Lp(a)-mediated vascular injury 1687:1716 Results suggest (1) possibility of a role for LIg in combating non-primate molecules and cells bearing TAG moiety and (2) a mechanism for Lp(a)-mediated vascular injury as diabetes, infections and inflammations induce greater release of neuraminidase into circulation. 24517196 5 28 theme LIg 865:867 arg1 binding 869:875 LIg binding 865:875 LIg binding to bovine thyroglobulin or rabbit RBC membrane proteins, both bearing TAG 865:949 LIg binding to bovine thyroglobulin or rabbit RBC membrane proteins, both bearing TAG was substantially reduced by prior treatment of the proteins with α-galactosidase to remove TAG though enzyme-treated glycans contained newly exposed LacNAc moieties. 24517196 7 29 gly desialylated 1264:1275 arg1 a 1229:1229 a 1229:1229 a 1229:1229 Unlike LDL, plasma lipoprotein(a) [Lp(a)] coated on polystyrene well and desialylated by neuraminidase was recognized by LIg through terminal LacNAc moieties exposed by the enzyme on its apo(a) subunit. 24517196 7 29 gly desialylated 1264:1275 arg1 [Lp 1225:1227 plasma lipoprotein(a) [Lp 1203:1227 plasma lipoprotein(a) [Lp(a)] coated on polystyrene well and desialylated by neuraminidase 1203:1292 Unlike LDL, plasma lipoprotein(a) [Lp(a)] coated on polystyrene well and desialylated by neuraminidase was recognized by LIg through terminal LacNAc moieties exposed by the enzyme on its apo(a) subunit. 24517196 0 30 gly desialylated 120:131 arg1 a 145:145 a 145:145 a 145:145 Dual specificity of human plasma lactose-binding immunoglobulin to anomers of terminal galactose enables recognition of desialylated lipoprotein(a) and xenoantigens. 24517196 0 30 gly desialylated 120:131 arg1 lipoprotein 133:143 desialylated lipoprotein 120:143 desialylated lipoprotein(a) 120:146 Dual specificity of human plasma lactose-binding immunoglobulin to anomers of terminal galactose enables recognition of desialylated lipoprotein(a) and xenoantigens. 24517196 7 31 theme LacNAc 1333:1338 arg1 moieties 1340:1347 terminal LacNAc moieties 1324:1347 terminal LacNAc moieties exposed by the enzyme on its apo(a) subunit 1324:1391 Unlike LDL, plasma lipoprotein(a) [Lp(a)] coated on polystyrene well and desialylated by neuraminidase was recognized by LIg through terminal LacNAc moieties exposed by the enzyme on its apo(a) subunit. 24517196 2 32 theme methyl 430:435 arg1 galactoside 437:447 methyl galactoside 430:447 methyl galactoside 430:447 LIg-mediated agglutination of desialylated human RBC was inhibited equally by the α- and β-anomers of methyl galactoside. 24517196 0 33 theme plasma 26:31 arg1 immunoglobulin 49:62 human plasma lactose-binding immunoglobulin 20:62 human plasma lactose-binding immunoglobulin 20:62 Dual specificity of human plasma lactose-binding immunoglobulin to anomers of terminal galactose enables recognition of desialylated lipoprotein(a) and xenoantigens. 24517196 7 34 theme plasma 1203:1208 arg1 a 1222:1222 a 1222:1222 a 1222:1222 Unlike LDL, plasma lipoprotein(a) [Lp(a)] coated on polystyrene well and desialylated by neuraminidase was recognized by LIg through terminal LacNAc moieties exposed by the enzyme on its apo(a) subunit. 24517196 7 34 theme plasma 1203:1208 arg1 lipoprotein 1210:1220 plasma lipoprotein 1203:1220 plasma lipoprotein(a) [Lp(a)] coated on polystyrene well and desialylated by neuraminidase 1203:1292 Unlike LDL, plasma lipoprotein(a) [Lp(a)] coated on polystyrene well and desialylated by neuraminidase was recognized by LIg through terminal LacNAc moieties exposed by the enzyme on its apo(a) subunit. 24517196 1 35 with IgG 285:287 arg1 contents 318:325 significant IgA and IgM contents 294:325 significant IgA and IgM contents 294:325 Human plasma lactose-binding immunoglobulin (LIg) isolated by affinity chromatography on lactose-Sepharose was largely IgG with significant IgA and IgM contents. 24517196 8 36 theme low 1531:1533 arg1 Lp 1535:1536 low Lp 1531:1536 low Lp(a) plasma 1531:1546 Further, same amount of added fluorescence-labelled LIg formed significantly more immune complex with Lp(a) in high Lp(a) plasma than in low Lp(a) plasma. 24517196 8 36 theme low 1531:1533 arg1 a 1538:1538 a 1538:1538 a 1538:1538 Further, same amount of added fluorescence-labelled LIg formed significantly more immune complex with Lp(a) in high Lp(a) plasma than in low Lp(a) plasma. 24517196 7 37 dep [Lp 1225:1227 arg1 desialylated 1264:1275 desialylated 1264:1275 desialylated by neuraminidase 1264:1292 Unlike LDL, plasma lipoprotein(a) [Lp(a)] coated on polystyrene well and desialylated by neuraminidase was recognized by LIg through terminal LacNAc moieties exposed by the enzyme on its apo(a) subunit. 24517196 7 37 dep [Lp 1225:1227 arg1 coated 1233:1238 coated 1233:1238 coated on polystyrene well 1233:1258 Unlike LDL, plasma lipoprotein(a) [Lp(a)] coated on polystyrene well and desialylated by neuraminidase was recognized by LIg through terminal LacNAc moieties exposed by the enzyme on its apo(a) subunit. 24517196 8 38 theme same 1403:1406 arg1 LIg 1446:1448 added fluorescence-labelled LIg 1418:1448 added fluorescence-labelled LIg 1418:1448 Further, same amount of added fluorescence-labelled LIg formed significantly more immune complex with Lp(a) in high Lp(a) plasma than in low Lp(a) plasma. 24517196 8 38 theme same 1403:1406 arg1 amount 1408:1413 same amount 1403:1413 same amount of added fluorescence-labelled LIg 1403:1448 Further, same amount of added fluorescence-labelled LIg formed significantly more immune complex with Lp(a) in high Lp(a) plasma than in low Lp(a) plasma. 24517196 3 39 theme glycans 514:520 arg1 Recognition 450:460 Recognition 450:460 Recognition of either the terminal α-galactose (TAG)-containing glycans of bovine thyroglobulin or the N-acetyl lactosamine (LacNAc)-terminating glycans of asialofetuin by LIg 450:624 Recognition of either the terminal α-galactose (TAG)-containing glycans of bovine thyroglobulin or the N-acetyl lactosamine (LacNAc)-terminating glycans of asialofetuin by LIg was inhibitable nearly as much by the α-galactoside melibiose as by the β-galactoside lactose. 24517196 0 40 theme immunoglobulin 49:62 arg1 specificity 5:15 Dual specificity 0:15 Dual specificity of human plasma lactose-binding immunoglobulin to anomers of terminal galactose 0:95 Dual specificity of human plasma lactose-binding immunoglobulin to anomers of terminal galactose enables recognition of desialylated lipoprotein(a) and xenoantigens. 24517196 6 41 gly Desialylated 1118:1129 arg1 oligosaccharides 1140:1155 Desialylated O-linked oligosaccharides 1118:1155 Desialylated O-linked oligosaccharides 1118:1155 Desialylated O-linked oligosaccharides, however, were no ligand for LIg. 24517196 3 42 theme β-galactoside 698:710 arg1 lactose 712:718 the β-galactoside lactose 694:718 the β-galactoside lactose 694:718 Recognition of either the terminal α-galactose (TAG)-containing glycans of bovine thyroglobulin or the N-acetyl lactosamine (LacNAc)-terminating glycans of asialofetuin by LIg was inhibitable nearly as much by the α-galactoside melibiose as by the β-galactoside lactose. 24517196 2 43 dep α- 410:411 arg1 the 406:408 the 406:408 the 406:408 LIg-mediated agglutination of desialylated human RBC was inhibited equally by the α- and β-anomers of methyl galactoside. 24517196 2 44 theme desialylated 358:369 arg1 RBC 377:379 desialylated human RBC 358:379 desialylated human RBC 358:379 LIg-mediated agglutination of desialylated human RBC was inhibited equally by the α- and β-anomers of methyl galactoside. 24517196 1 45 theme affinity 228:235 arg1 chromatography 237:250 affinity chromatography 228:250 affinity chromatography on lactose-Sepharose 228:271 Human plasma lactose-binding immunoglobulin (LIg) isolated by affinity chromatography on lactose-Sepharose was largely IgG with significant IgA and IgM contents. 24517196 8 46 theme fluorescence-labelled 1424:1444 arg1 LIg 1446:1448 added fluorescence-labelled LIg 1418:1448 added fluorescence-labelled LIg 1418:1448 Further, same amount of added fluorescence-labelled LIg formed significantly more immune complex with Lp(a) in high Lp(a) plasma than in low Lp(a) plasma. 24517196 5 47 theme rabbit 904:909 arg1 RBC 911:913 rabbit RBC 904:913 rabbit RBC 904:913 LIg binding to bovine thyroglobulin or rabbit RBC membrane proteins, both bearing TAG was substantially reduced by prior treatment of the proteins with α-galactosidase to remove TAG though enzyme-treated glycans contained newly exposed LacNAc moieties. 24517196 9 48 theme greater 1767:1773 arg1 release 1775:1781 greater release 1767:1781 greater release of neuraminidase into circulation 1767:1815 Results suggest (1) possibility of a role for LIg in combating non-primate molecules and cells bearing TAG moiety and (2) a mechanism for Lp(a)-mediated vascular injury as diabetes, infections and inflammations induce greater release of neuraminidase into circulation. 24517196 3 49 theme bovine 525:530 arg1 thyroglobulin 532:544 bovine thyroglobulin 525:544 bovine thyroglobulin 525:544 Recognition of either the terminal α-galactose (TAG)-containing glycans of bovine thyroglobulin or the N-acetyl lactosamine (LacNAc)-terminating glycans of asialofetuin by LIg was inhibitable nearly as much by the α-galactoside melibiose as by the β-galactoside lactose. 24517196 9 50 theme role 1586:1589 arg1 possibility 1569:1579 (1) possibility 1565:1579 (1) possibility of a role for LIg in combating non-primate molecules and cells bearing TAG moiety and (2) a mechanism for Lp(a)-mediated vascular injury as diabetes, infections and inflammations 1565:1758 Results suggest (1) possibility of a role for LIg in combating non-primate molecules and cells bearing TAG moiety and (2) a mechanism for Lp(a)-mediated vascular injury as diabetes, infections and inflammations induce greater release of neuraminidase into circulation. 24517196 2 51 theme RBC 377:379 arg1 agglutination 341:353 LIg-mediated agglutination 328:353 LIg-mediated agglutination of desialylated human RBC 328:379 LIg-mediated agglutination of desialylated human RBC was inhibited equally by the α- and β-anomers of methyl galactoside. 24517196 1 52 theme plasma 172:177 arg1 immunoglobulin 195:208 Human plasma lactose-binding immunoglobulin 166:208 Human plasma lactose-binding immunoglobulin (LIg) isolated by affinity chromatography on lactose-Sepharose 166:271 Human plasma lactose-binding immunoglobulin (LIg) isolated by affinity chromatography on lactose-Sepharose was largely IgG with significant IgA and IgM contents. 24517196 1 52 theme plasma 172:177 arg1 LIg 211:213 LIg 211:213 LIg 211:213 Human plasma lactose-binding immunoglobulin (LIg) isolated by affinity chromatography on lactose-Sepharose was largely IgG with significant IgA and IgM contents. 24517196 5 53 with treatment 986:994 arg1 α-galactosidase 1017:1031 α-galactosidase 1017:1031 α-galactosidase 1017:1031 LIg binding to bovine thyroglobulin or rabbit RBC membrane proteins, both bearing TAG was substantially reduced by prior treatment of the proteins with α-galactosidase to remove TAG though enzyme-treated glycans contained newly exposed LacNAc moieties. 24517196 3 54 theme glycans 595:601 arg1 Recognition 450:460 Recognition 450:460 Recognition of either the terminal α-galactose (TAG)-containing glycans of bovine thyroglobulin or the N-acetyl lactosamine (LacNAc)-terminating glycans of asialofetuin by LIg 450:624 Recognition of either the terminal α-galactose (TAG)-containing glycans of bovine thyroglobulin or the N-acetyl lactosamine (LacNAc)-terminating glycans of asialofetuin by LIg was inhibitable nearly as much by the α-galactoside melibiose as by the β-galactoside lactose. 24517196 5 55 theme RBC 911:913 arg1 both 934:937 both 934:937 both 934:937 LIg binding to bovine thyroglobulin or rabbit RBC membrane proteins, both bearing TAG was substantially reduced by prior treatment of the proteins with α-galactosidase to remove TAG though enzyme-treated glycans contained newly exposed LacNAc moieties. 24517196 5 55 theme RBC 911:913 arg1 proteins 924:931 bovine thyroglobulin or rabbit RBC membrane proteins 880:931 bovine thyroglobulin or rabbit RBC membrane proteins 880:931 LIg binding to bovine thyroglobulin or rabbit RBC membrane proteins, both bearing TAG was substantially reduced by prior treatment of the proteins with α-galactosidase to remove TAG though enzyme-treated glycans contained newly exposed LacNAc moieties. 24517196 5 56 theme bovine 880:885 arg1 thyroglobulin 887:899 bovine thyroglobulin 880:899 bovine thyroglobulin 880:899 LIg binding to bovine thyroglobulin or rabbit RBC membrane proteins, both bearing TAG was substantially reduced by prior treatment of the proteins with α-galactosidase to remove TAG though enzyme-treated glycans contained newly exposed LacNAc moieties. 24517196 8 57 theme more 1471:1474 arg1 complex 1483:1489 significantly more immune complex 1457:1489 significantly more immune complex with Lp(a) in high Lp(a) plasma 1457:1521 Further, same amount of added fluorescence-labelled LIg formed significantly more immune complex with Lp(a) in high Lp(a) plasma than in low Lp(a) plasma. 24517196 0 58 theme xenoantigens 152:163 arg1 recognition 105:115 recognition 105:115 recognition of desialylated lipoprotein(a) and xenoantigens 105:163 Dual specificity of human plasma lactose-binding immunoglobulin to anomers of terminal galactose enables recognition of desialylated lipoprotein(a) and xenoantigens. 24517196 3 59 theme asialofetuin 606:617 arg1 glycans 514:520 the terminal α-galactose (TAG)-containing glycans 472:520 the terminal α-galactose (TAG)-containing glycans of bovine thyroglobulin 472:544 Recognition of either the terminal α-galactose (TAG)-containing glycans of bovine thyroglobulin or the N-acetyl lactosamine (LacNAc)-terminating glycans of asialofetuin by LIg was inhibitable nearly as much by the α-galactoside melibiose as by the β-galactoside lactose. 24517196 3 59 theme asialofetuin 606:617 arg1 glycans 595:601 the N-acetyl lactosamine (LacNAc)-terminating glycans 549:601 the N-acetyl lactosamine (LacNAc)-terminating glycans of asialofetuin 549:617 Recognition of either the terminal α-galactose (TAG)-containing glycans of bovine thyroglobulin or the N-acetyl lactosamine (LacNAc)-terminating glycans of asialofetuin by LIg was inhibitable nearly as much by the α-galactoside melibiose as by the β-galactoside lactose. 24517196 9 60 theme TAG 1652:1654 arg1 moiety 1656:1661 TAG moiety 1652:1661 TAG moiety 1652:1661 Results suggest (1) possibility of a role for LIg in combating non-primate molecules and cells bearing TAG moiety and (2) a mechanism for Lp(a)-mediated vascular injury as diabetes, infections and inflammations induce greater release of neuraminidase into circulation. 24517196 7 61 theme a 1382:1382 arg1 subunit 1385:1391 its apo(a) subunit 1374:1391 its apo(a) subunit 1374:1391 Unlike LDL, plasma lipoprotein(a) [Lp(a)] coated on polystyrene well and desialylated by neuraminidase was recognized by LIg through terminal LacNAc moieties exposed by the enzyme on its apo(a) subunit. 24517196 9 62 dep mechanism 1673:1681 arg1 2 1668:1668 2 1668:1668 2 1668:1668 Results suggest (1) possibility of a role for LIg in combating non-primate molecules and cells bearing TAG moiety and (2) a mechanism for Lp(a)-mediated vascular injury as diabetes, infections and inflammations induce greater release of neuraminidase into circulation. 24517196 5 63 theme LacNAc 1101:1106 arg1 moieties 1108:1115 newly exposed LacNAc moieties 1087:1115 newly exposed LacNAc moieties 1087:1115 LIg binding to bovine thyroglobulin or rabbit RBC membrane proteins, both bearing TAG was substantially reduced by prior treatment of the proteins with α-galactosidase to remove TAG though enzyme-treated glycans contained newly exposed LacNAc moieties. 24517196 7 64 theme apo 1378:1380 arg1 subunit 1385:1391 its apo(a) subunit 1374:1391 its apo(a) subunit 1374:1391 Unlike LDL, plasma lipoprotein(a) [Lp(a)] coated on polystyrene well and desialylated by neuraminidase was recognized by LIg through terminal LacNAc moieties exposed by the enzyme on its apo(a) subunit. 24517196 4 65 dep more 819:822 arg1 molecules 828:836 LIg molecules 824:836 LIg molecules 824:836 Melibiose covalently conjugated to protein and coated on polystyrene wells captured several times more LIg molecules than its lactose analogue. 24517196 0 66 theme galactose 87:95 arg1 anomers 67:73 anomers 67:73 anomers of terminal galactose 67:95 Dual specificity of human plasma lactose-binding immunoglobulin to anomers of terminal galactose enables recognition of desialylated lipoprotein(a) and xenoantigens. 24517196 8 67 from Lp 1496:1497 arg1 plasma 1516:1521 high Lp(a) plasma 1505:1521 high Lp(a) plasma 1505:1521 Further, same amount of added fluorescence-labelled LIg formed significantly more immune complex with Lp(a) in high Lp(a) plasma than in low Lp(a) plasma. 24517196 9 68 dep possibility 1569:1579 arg1 1 1566:1566 1 1566:1566 1 1566:1566 Results suggest (1) possibility of a role for LIg in combating non-primate molecules and cells bearing TAG moiety and (2) a mechanism for Lp(a)-mediated vascular injury as diabetes, infections and inflammations induce greater release of neuraminidase into circulation. 24517196 8 69 theme Lp 1510:1511 arg1 plasma 1516:1521 high Lp(a) plasma 1505:1521 high Lp(a) plasma 1505:1521 Further, same amount of added fluorescence-labelled LIg formed significantly more immune complex with Lp(a) in high Lp(a) plasma than in low Lp(a) plasma. 24517196 4 70 dep Melibiose 721:729 arg1 coated 768:773 coated 768:773 coated on polystyrene wells 768:794 Melibiose covalently conjugated to protein and coated on polystyrene wells captured several times more LIg molecules than its lactose analogue. 24517196 4 70 dep Melibiose 721:729 arg1 conjugated 742:751 conjugated 742:751 covalently conjugated to protein 731:762 Melibiose covalently conjugated to protein and coated on polystyrene wells captured several times more LIg molecules than its lactose analogue. 24517196 0 71 theme desialylated 120:131 arg1 a 145:145 a 145:145 a 145:145 Dual specificity of human plasma lactose-binding immunoglobulin to anomers of terminal galactose enables recognition of desialylated lipoprotein(a) and xenoantigens. 24517196 0 71 theme desialylated 120:131 arg1 lipoprotein 133:143 desialylated lipoprotein 120:143 desialylated lipoprotein(a) 120:146 Dual specificity of human plasma lactose-binding immunoglobulin to anomers of terminal galactose enables recognition of desialylated lipoprotein(a) and xenoantigens. 24517196 6 72 theme O-linked 1131:1138 arg1 oligosaccharides 1140:1155 Desialylated O-linked oligosaccharides 1118:1155 Desialylated O-linked oligosaccharides 1118:1155 Desialylated O-linked oligosaccharides, however, were no ligand for LIg. 24517196 0 73 theme human 20:24 arg1 immunoglobulin 49:62 human plasma lactose-binding immunoglobulin 20:62 human plasma lactose-binding immunoglobulin 20:62 Dual specificity of human plasma lactose-binding immunoglobulin to anomers of terminal galactose enables recognition of desialylated lipoprotein(a) and xenoantigens. 24517196 1 74 theme IgA 306:308 arg1 contents 318:325 significant IgA and IgM contents 294:325 significant IgA and IgM contents 294:325 Human plasma lactose-binding immunoglobulin (LIg) isolated by affinity chromatography on lactose-Sepharose was largely IgG with significant IgA and IgM contents. 24517196 7 75 theme terminal 1324:1331 arg1 moieties 1340:1347 terminal LacNAc moieties 1324:1347 terminal LacNAc moieties exposed by the enzyme on its apo(a) subunit 1324:1391 Unlike LDL, plasma lipoprotein(a) [Lp(a)] coated on polystyrene well and desialylated by neuraminidase was recognized by LIg through terminal LacNAc moieties exposed by the enzyme on its apo(a) subunit. 24517196 9 76 theme vascular 1702:1709 arg1 injury 1711:1716 Lp(a)-mediated vascular injury 1687:1716 Lp(a)-mediated vascular injury 1687:1716 Results suggest (1) possibility of a role for LIg in combating non-primate molecules and cells bearing TAG moiety and (2) a mechanism for Lp(a)-mediated vascular injury as diabetes, infections and inflammations induce greater release of neuraminidase into circulation. 24517196 3 77 theme α-galactoside 664:676 arg1 melibiose 678:686 the α-galactoside melibiose 660:686 the α-galactoside melibiose as by the β-galactoside lactose 660:718 Recognition of either the terminal α-galactose (TAG)-containing glycans of bovine thyroglobulin or the N-acetyl lactosamine (LacNAc)-terminating glycans of asialofetuin by LIg was inhibitable nearly as much by the α-galactoside melibiose as by the β-galactoside lactose. 24517196 4 78 theme polystyrene 778:788 arg1 wells 790:794 polystyrene wells 778:794 polystyrene wells 778:794 Melibiose covalently conjugated to protein and coated on polystyrene wells captured several times more LIg molecules than its lactose analogue. 24517196 2 79 theme galactoside 437:447 arg1 β-anomers 417:425 β-anomers 417:425 β-anomers 417:425 LIg-mediated agglutination of desialylated human RBC was inhibited equally by the α- and β-anomers of methyl galactoside. 24517196 2 79 theme galactoside 437:447 arg1 α- 410:411 α- 410:411 α- 410:411 LIg-mediated agglutination of desialylated human RBC was inhibited equally by the α- and β-anomers of methyl galactoside. 24517196 0 80 theme lactose-binding 33:47 arg1 immunoglobulin 49:62 human plasma lactose-binding immunoglobulin 20:62 human plasma lactose-binding immunoglobulin 20:62 Dual specificity of human plasma lactose-binding immunoglobulin to anomers of terminal galactose enables recognition of desialylated lipoprotein(a) and xenoantigens. 24517196 1 81 theme IgM 314:316 arg1 contents 318:325 significant IgA and IgM contents 294:325 significant IgA and IgM contents 294:325 Human plasma lactose-binding immunoglobulin (LIg) isolated by affinity chromatography on lactose-Sepharose was largely IgG with significant IgA and IgM contents. 24517196 5 82 theme enzyme-treated 1054:1067 arg1 glycans 1069:1075 enzyme-treated glycans 1054:1075 enzyme-treated glycans 1054:1075 LIg binding to bovine thyroglobulin or rabbit RBC membrane proteins, both bearing TAG was substantially reduced by prior treatment of the proteins with α-galactosidase to remove TAG though enzyme-treated glycans contained newly exposed LacNAc moieties. 24517196 8 83 theme Lp 1535:1536 arg1 plasma 1541:1546 low Lp(a) plasma 1531:1546 low Lp(a) plasma 1531:1546 Further, same amount of added fluorescence-labelled LIg formed significantly more immune complex with Lp(a) in high Lp(a) plasma than in low Lp(a) plasma. 24517196 4 84 theme lactose 847:853 arg1 analogue 855:862 its lactose analogue 843:862 its lactose analogue 843:862 Melibiose covalently conjugated to protein and coated on polystyrene wells captured several times more LIg molecules than its lactose analogue. 24517196 2 85 theme human 371:375 arg1 RBC 377:379 desialylated human RBC 358:379 desialylated human RBC 358:379 LIg-mediated agglutination of desialylated human RBC was inhibited equally by the α- and β-anomers of methyl galactoside. 24517196 5 86 contain contained 1077:1085 arg1 glycans 1069:1075 enzyme-treated glycans 1054:1075 enzyme-treated glycans 1054:1075 LIg binding to bovine thyroglobulin or rabbit RBC membrane proteins, both bearing TAG was substantially reduced by prior treatment of the proteins with α-galactosidase to remove TAG though enzyme-treated glycans contained newly exposed LacNAc moieties. 24517196 5 86 contain contained 1077:1085 arg2 moieties 1108:1115 newly exposed LacNAc moieties 1087:1115 newly exposed LacNAc moieties 1087:1115 LIg binding to bovine thyroglobulin or rabbit RBC membrane proteins, both bearing TAG was substantially reduced by prior treatment of the proteins with α-galactosidase to remove TAG though enzyme-treated glycans contained newly exposed LacNAc moieties. 24517196 2 87 gly desialylated 358:369 arg1 RBC 377:379 desialylated human RBC 358:379 desialylated human RBC 358:379 LIg-mediated agglutination of desialylated human RBC was inhibited equally by the α- and β-anomers of methyl galactoside. 24517196 4 88 theme LIg 824:826 arg1 molecules 828:836 LIg molecules 824:836 LIg molecules 824:836 Melibiose covalently conjugated to protein and coated on polystyrene wells captured several times more LIg molecules than its lactose analogue. 24517196 3 89 theme -containing 502:512 arg1 glycans 514:520 the terminal α-galactose (TAG)-containing glycans 472:520 the terminal α-galactose (TAG)-containing glycans of bovine thyroglobulin 472:544 Recognition of either the terminal α-galactose (TAG)-containing glycans of bovine thyroglobulin or the N-acetyl lactosamine (LacNAc)-terminating glycans of asialofetuin by LIg was inhibitable nearly as much by the α-galactoside melibiose as by the β-galactoside lactose. 24517196 6 90 link O-linked 1131:1138 arg1 oligosaccharides 1140:1155 Desialylated O-linked oligosaccharides 1118:1155 Desialylated O-linked oligosaccharides 1118:1155 Desialylated O-linked oligosaccharides, however, were no ligand for LIg. 24517196 8 91 theme added 1418:1422 arg1 LIg 1446:1448 added fluorescence-labelled LIg 1418:1448 added fluorescence-labelled LIg 1418:1448 Further, same amount of added fluorescence-labelled LIg formed significantly more immune complex with Lp(a) in high Lp(a) plasma than in low Lp(a) plasma. 24225132 0 0 theme site 100:103 arg1 prediction 105:114 glycosylation site prediction 86:114 glycosylation site prediction 86:114 HMMpTM: improving transmembrane protein topology prediction using phosphorylation and glycosylation site prediction. 24225132 4 1 theme glycosylation 755:767 arg1 prediction 774:783 glycosylation site prediction 755:783 glycosylation site prediction 755:783 We examine the combination of phosphorylation and glycosylation site prediction with transmembrane protein topology prediction. 24225132 4 2 theme prediction 774:783 arg1 combination 720:730 the combination 716:730 the combination of phosphorylation and glycosylation site prediction with transmembrane protein topology prediction 716:830 We examine the combination of phosphorylation and glycosylation site prediction with transmembrane protein topology prediction. 24225132 0 3 theme glycosylation 86:98 arg1 prediction 105:114 glycosylation site prediction 86:114 glycosylation site prediction 86:114 HMMpTM: improving transmembrane protein topology prediction using phosphorylation and glycosylation site prediction. 24225132 5 4 theme kinase 980:985 arg1 phosphorylation 996:1010 kinase specific phosphorylation and N/O-linked glycosylation sites 980:1045 phosphorylation 996:1010 We report the development of a Hidden Markov Model based method, capable of predicting the topology of transmembrane proteins and the existence of kinase specific phosphorylation and N/O-linked glycosylation sites along the protein sequence. 24225132 2 5 theme residues 369:376 arg1 distribution 334:345 the distribution 330:345 the distribution of positively charged residues in extra-membrane loops and the existence of N-terminal signals 330:440 Current predictors rely on topogenic signals in the protein sequence, such as the distribution of positively charged residues in extra-membrane loops and the existence of N-terminal signals. 24225132 6 6 theme novel 1099:1103 arg1 feature 1105:1111 a novel feature 1097:1111 a novel feature 1097:1111 Our method integrates a novel feature in transmembrane protein topology prediction, which results in improved performance for topology prediction and reliable prediction of phosphorylation and glycosylation sites. 24225132 3 7 theme post-translational 490:507 arg1 PTMs 524:527 PTMs 524:527 PTMs 524:527 However, phosphorylation and glycosylation are post-translational modifications (PTMs) that occur in a compartment-specific manner and therefore the presence of a phosphorylation or glycosylation site in a transmembrane protein provides topological information. 24225132 3 7 theme post-translational 490:507 arg1 glycosylation 472:484 glycosylation 472:484 glycosylation 472:484 However, phosphorylation and glycosylation are post-translational modifications (PTMs) that occur in a compartment-specific manner and therefore the presence of a phosphorylation or glycosylation site in a transmembrane protein provides topological information. 24225132 3 7 theme post-translational 490:507 arg1 modifications 509:521 post-translational modifications 490:521 post-translational modifications (PTMs) that occur in a compartment-specific manner and therefore the presence of a phosphorylation or glycosylation site in a transmembrane protein provides topological information 490:702 However, phosphorylation and glycosylation are post-translational modifications (PTMs) that occur in a compartment-specific manner and therefore the presence of a phosphorylation or glycosylation site in a transmembrane protein provides topological information. 24225132 3 7 theme post-translational 490:507 arg1 phosphorylation 452:466 phosphorylation 452:466 phosphorylation 452:466 However, phosphorylation and glycosylation are post-translational modifications (PTMs) that occur in a compartment-specific manner and therefore the presence of a phosphorylation or glycosylation site in a transmembrane protein provides topological information. 24225132 3 8 theme topological 680:690 arg1 information 692:702 topological information 680:702 topological information 680:702 However, phosphorylation and glycosylation are post-translational modifications (PTMs) that occur in a compartment-specific manner and therefore the presence of a phosphorylation or glycosylation site in a transmembrane protein provides topological information. 24225132 2 9 from distribution 334:345 arg1 loops 396:400 extra-membrane loops 381:400 extra-membrane loops 381:400 Current predictors rely on topogenic signals in the protein sequence, such as the distribution of positively charged residues in extra-membrane loops and the existence of N-terminal signals. 24225132 3 10 from presence 592:599 arg1 protein 663:669 a transmembrane protein 647:669 a transmembrane protein provides topological information 647:702 However, phosphorylation and glycosylation are post-translational modifications (PTMs) that occur in a compartment-specific manner and therefore the presence of a phosphorylation or glycosylation site in a transmembrane protein provides topological information. 24225132 5 11 theme sites 1041:1045 arg1 topology 924:931 the topology 920:931 the topology of transmembrane proteins 920:957 We report the development of a Hidden Markov Model based method, capable of predicting the topology of transmembrane proteins and the existence of kinase specific phosphorylation and N/O-linked glycosylation sites along the protein sequence. 24225132 5 11 theme sites 1041:1045 arg1 existence 967:975 the existence 963:975 the existence of kinase specific phosphorylation and N/O-linked glycosylation sites along the protein sequence 963:1072 We report the development of a Hidden Markov Model based method, capable of predicting the topology of transmembrane proteins and the existence of kinase specific phosphorylation and N/O-linked glycosylation sites along the protein sequence. 24225132 2 12 theme protein 304:310 arg1 sequence 312:319 the protein sequence 300:319 the protein sequence 300:319 Current predictors rely on topogenic signals in the protein sequence, such as the distribution of positively charged residues in extra-membrane loops and the existence of N-terminal signals. 24225132 3 13 gly glycosylation 625:637 arg2 site 639:642 a phosphorylation or glycosylation site 604:642 site 639:642 However, phosphorylation and glycosylation are post-translational modifications (PTMs) that occur in a compartment-specific manner and therefore the presence of a phosphorylation or glycosylation site in a transmembrane protein provides topological information. 24225132 5 14 theme glycosylation 1027:1039 arg1 sites 1041:1045 kinase specific phosphorylation and N/O-linked glycosylation sites 980:1045 sites 1041:1045 We report the development of a Hidden Markov Model based method, capable of predicting the topology of transmembrane proteins and the existence of kinase specific phosphorylation and N/O-linked glycosylation sites along the protein sequence. 24225132 4 15 theme site 769:772 arg1 prediction 774:783 glycosylation site prediction 755:783 glycosylation site prediction 755:783 We examine the combination of phosphorylation and glycosylation site prediction with transmembrane protein topology prediction. 24225132 2 16 theme charged 361:367 arg1 signals 434:440 N-terminal signals 423:440 N-terminal signals 423:440 Current predictors rely on topogenic signals in the protein sequence, such as the distribution of positively charged residues in extra-membrane loops and the existence of N-terminal signals. 24225132 2 16 theme charged 361:367 arg1 residues 369:376 positively charged residues 350:376 positively charged residues in extra-membrane loops 350:400 Current predictors rely on topogenic signals in the protein sequence, such as the distribution of positively charged residues in extra-membrane loops and the existence of N-terminal signals. 24225132 3 17 dep protein 663:669 arg1 provides 671:678 provides 671:678 provides topological information 671:702 However, phosphorylation and glycosylation are post-translational modifications (PTMs) that occur in a compartment-specific manner and therefore the presence of a phosphorylation or glycosylation site in a transmembrane protein provides topological information. 24225132 0 18 gly glycosylation 86:98 arg2 site 100:103 glycosylation site prediction 86:114 glycosylation site prediction 86:114 HMMpTM: improving transmembrane protein topology prediction using phosphorylation and glycosylation site prediction. 24225132 0 18 gly glycosylation 86:98 arg2 prediction 105:114 glycosylation site prediction 86:114 glycosylation site prediction 86:114 HMMpTM: improving transmembrane protein topology prediction using phosphorylation and glycosylation site prediction. 24225132 6 19 theme improved 1176:1183 arg1 performance 1185:1195 improved performance 1176:1195 improved performance for topology prediction and reliable prediction of phosphorylation and glycosylation sites 1176:1286 Our method integrates a novel feature in transmembrane protein topology prediction, which results in improved performance for topology prediction and reliable prediction of phosphorylation and glycosylation sites. 24225132 1 20 theme methods 177:183 arg1 number 153:158 a large number 145:158 a large number of computational methods 145:183 During the last two decades a large number of computational methods have been developed for predicting transmembrane protein topology. 24225132 5 21 theme specific 987:994 arg1 phosphorylation 996:1010 kinase specific phosphorylation and N/O-linked glycosylation sites 980:1045 phosphorylation 996:1010 We report the development of a Hidden Markov Model based method, capable of predicting the topology of transmembrane proteins and the existence of kinase specific phosphorylation and N/O-linked glycosylation sites along the protein sequence. 24225132 6 22 theme protein 1130:1136 arg1 prediction 1147:1156 transmembrane protein topology prediction 1116:1156 transmembrane protein topology prediction 1116:1156 Our method integrates a novel feature in transmembrane protein topology prediction, which results in improved performance for topology prediction and reliable prediction of phosphorylation and glycosylation sites. 24225132 6 23 theme topology 1201:1208 arg1 prediction 1210:1219 topology prediction 1201:1219 topology prediction 1201:1219 Our method integrates a novel feature in transmembrane protein topology prediction, which results in improved performance for topology prediction and reliable prediction of phosphorylation and glycosylation sites. 24225132 2 24 theme existence 410:418 arg1 distribution 334:345 the distribution 330:345 the distribution of positively charged residues in extra-membrane loops and the existence of N-terminal signals 330:440 Current predictors rely on topogenic signals in the protein sequence, such as the distribution of positively charged residues in extra-membrane loops and the existence of N-terminal signals. 24225132 6 25 from feature 1105:1111 arg1 prediction 1147:1156 transmembrane protein topology prediction 1116:1156 transmembrane protein topology prediction 1116:1156 Our method integrates a novel feature in transmembrane protein topology prediction, which results in improved performance for topology prediction and reliable prediction of phosphorylation and glycosylation sites. 24225132 2 26 from residues 369:376 arg1 loops 396:400 extra-membrane loops 381:400 extra-membrane loops 381:400 Current predictors rely on topogenic signals in the protein sequence, such as the distribution of positively charged residues in extra-membrane loops and the existence of N-terminal signals. 24225132 3 27 theme phosphorylation 606:620 arg1 site 639:642 a phosphorylation or glycosylation site 604:642 site 639:642 However, phosphorylation and glycosylation are post-translational modifications (PTMs) that occur in a compartment-specific manner and therefore the presence of a phosphorylation or glycosylation site in a transmembrane protein provides topological information. 24225132 4 28 theme phosphorylation 735:749 arg1 combination 720:730 the combination 716:730 the combination of phosphorylation and glycosylation site prediction with transmembrane protein topology prediction 716:830 We examine the combination of phosphorylation and glycosylation site prediction with transmembrane protein topology prediction. 24225132 2 29 from loops 396:400 arg1 distribution 334:345 the distribution 330:345 the distribution of positively charged residues in extra-membrane loops and the existence of N-terminal signals 330:440 Current predictors rely on topogenic signals in the protein sequence, such as the distribution of positively charged residues in extra-membrane loops and the existence of N-terminal signals. 24225132 3 30 attach presence 592:599 arg1 protein 663:669 a transmembrane protein 647:669 a transmembrane protein provides topological information 647:702 However, phosphorylation and glycosylation are post-translational modifications (PTMs) that occur in a compartment-specific manner and therefore the presence of a phosphorylation or glycosylation site in a transmembrane protein provides topological information. 24225132 3 30 attach presence 592:599 arg2 site 639:642 a phosphorylation or glycosylation site 604:642 site 639:642 However, phosphorylation and glycosylation are post-translational modifications (PTMs) that occur in a compartment-specific manner and therefore the presence of a phosphorylation or glycosylation site in a transmembrane protein provides topological information. 24225132 7 31 from http 1323:1326 arg1 method 1293:1298 The method 1289:1298 The method 1289:1298 The method is freely available at http://bioinformatics.biol.uoa.gr/HMMpTM. 24225132 7 31 from http 1323:1326 arg1 available 1310:1318 available 1310:1318 available 1310:1318 The method is freely available at http://bioinformatics.biol.uoa.gr/HMMpTM. 24225132 0 32 theme transmembrane 18:30 arg1 prediction 49:58 transmembrane protein topology prediction 18:58 transmembrane protein topology prediction 18:58 HMMpTM: improving transmembrane protein topology prediction using phosphorylation and glycosylation site prediction. 24225132 5 33 theme capable 898:904 arg1 method 890:895 method 890:895 method 890:895 We report the development of a Hidden Markov Model based method, capable of predicting the topology of transmembrane proteins and the existence of kinase specific phosphorylation and N/O-linked glycosylation sites along the protein sequence. 24225132 5 34 theme protein 1057:1063 arg1 sequence 1065:1072 the protein sequence 1053:1072 the protein sequence 1053:1072 We report the development of a Hidden Markov Model based method, capable of predicting the topology of transmembrane proteins and the existence of kinase specific phosphorylation and N/O-linked glycosylation sites along the protein sequence. 24225132 1 35 theme computational 163:175 arg1 methods 177:183 computational methods 163:183 computational methods 163:183 During the last two decades a large number of computational methods have been developed for predicting transmembrane protein topology. 24225132 2 36 from signals 289:295 arg1 sequence 312:319 the protein sequence 300:319 the protein sequence 300:319 Current predictors rely on topogenic signals in the protein sequence, such as the distribution of positively charged residues in extra-membrane loops and the existence of N-terminal signals. 24225132 3 37 theme compartment-specific 546:565 arg1 manner 567:572 a compartment-specific manner 544:572 a compartment-specific manner 544:572 However, phosphorylation and glycosylation are post-translational modifications (PTMs) that occur in a compartment-specific manner and therefore the presence of a phosphorylation or glycosylation site in a transmembrane protein provides topological information. 24225132 0 38 theme topology 40:47 arg1 prediction 49:58 transmembrane protein topology prediction 18:58 transmembrane protein topology prediction 18:58 HMMpTM: improving transmembrane protein topology prediction using phosphorylation and glycosylation site prediction. 24225132 5 39 gly glycosylation 1027:1039 arg2 sites 1041:1045 kinase specific phosphorylation and N/O-linked glycosylation sites 980:1045 sites 1041:1045 We report the development of a Hidden Markov Model based method, capable of predicting the topology of transmembrane proteins and the existence of kinase specific phosphorylation and N/O-linked glycosylation sites along the protein sequence. 24225132 1 40 theme transmembrane 220:232 arg1 topology 242:249 transmembrane protein topology 220:249 transmembrane protein topology 220:249 During the last two decades a large number of computational methods have been developed for predicting transmembrane protein topology. 24225132 2 41 theme signals 434:440 arg1 existence 410:418 the existence 406:418 the existence of N-terminal signals 406:440 Current predictors rely on topogenic signals in the protein sequence, such as the distribution of positively charged residues in extra-membrane loops and the existence of N-terminal signals. 24225132 2 41 theme signals 434:440 arg1 signals 434:440 N-terminal signals 423:440 N-terminal signals 423:440 Current predictors rely on topogenic signals in the protein sequence, such as the distribution of positively charged residues in extra-membrane loops and the existence of N-terminal signals. 24225132 2 41 theme signals 434:440 arg1 residues 369:376 positively charged residues 350:376 positively charged residues in extra-membrane loops 350:400 Current predictors rely on topogenic signals in the protein sequence, such as the distribution of positively charged residues in extra-membrane loops and the existence of N-terminal signals. 24225132 0 42 theme protein 32:38 arg1 prediction 49:58 transmembrane protein topology prediction 18:58 transmembrane protein topology prediction 18:58 HMMpTM: improving transmembrane protein topology prediction using phosphorylation and glycosylation site prediction. 24225132 5 43 theme Markov 871:876 arg1 Model 878:882 a Hidden Markov Model 862:882 a Hidden Markov Model based method, capable of predicting the topology of transmembrane proteins and the existence of kinase specific phosphorylation and N/O-linked glycosylation sites along the protein sequence 862:1072 We report the development of a Hidden Markov Model based method, capable of predicting the topology of transmembrane proteins and the existence of kinase specific phosphorylation and N/O-linked glycosylation sites along the protein sequence. 24225132 4 44 with combination 720:730 arg1 prediction 821:830 transmembrane protein topology prediction 790:830 transmembrane protein topology prediction 790:830 We examine the combination of phosphorylation and glycosylation site prediction with transmembrane protein topology prediction. 24225132 2 45 theme Current 252:258 arg1 predictors 260:269 Current predictors 252:269 Current predictors 252:269 Current predictors rely on topogenic signals in the protein sequence, such as the distribution of positively charged residues in extra-membrane loops and the existence of N-terminal signals. 24225132 1 46 theme protein 234:240 arg1 topology 242:249 transmembrane protein topology 220:249 transmembrane protein topology 220:249 During the last two decades a large number of computational methods have been developed for predicting transmembrane protein topology. 24225132 5 47 theme Model 878:882 arg1 development 847:857 the development 843:857 the development of a Hidden Markov Model based method, capable of predicting the topology of transmembrane proteins and the existence of kinase specific phosphorylation and N/O-linked glycosylation sites along the protein sequence 843:1072 We report the development of a Hidden Markov Model based method, capable of predicting the topology of transmembrane proteins and the existence of kinase specific phosphorylation and N/O-linked glycosylation sites along the protein sequence. 24225132 5 48 link N/O-linked 1016:1025 arg1 sites 1041:1045 kinase specific phosphorylation and N/O-linked glycosylation sites 980:1045 sites 1041:1045 We report the development of a Hidden Markov Model based method, capable of predicting the topology of transmembrane proteins and the existence of kinase specific phosphorylation and N/O-linked glycosylation sites along the protein sequence. 24225132 3 49 theme glycosylation 625:637 arg1 site 639:642 a phosphorylation or glycosylation site 604:642 site 639:642 However, phosphorylation and glycosylation are post-translational modifications (PTMs) that occur in a compartment-specific manner and therefore the presence of a phosphorylation or glycosylation site in a transmembrane protein provides topological information. 24225132 6 50 theme reliable 1225:1232 arg1 prediction 1234:1243 reliable prediction 1225:1243 reliable prediction 1225:1243 Our method integrates a novel feature in transmembrane protein topology prediction, which results in improved performance for topology prediction and reliable prediction of phosphorylation and glycosylation sites. 24225132 1 51 theme last 128:131 arg1 decades 137:143 the last two decades 124:143 the last two decades 124:143 During the last two decades a large number of computational methods have been developed for predicting transmembrane protein topology. 24225132 4 52 gly glycosylation 755:767 arg2 prediction 774:783 glycosylation site prediction 755:783 glycosylation site prediction 755:783 We examine the combination of phosphorylation and glycosylation site prediction with transmembrane protein topology prediction. 24225132 4 52 gly glycosylation 755:767 arg2 site 769:772 glycosylation site prediction 755:783 glycosylation site prediction 755:783 We examine the combination of phosphorylation and glycosylation site prediction with transmembrane protein topology prediction. 24225132 3 53 theme site 639:642 arg1 presence 592:599 the presence 588:599 the presence of a phosphorylation or glycosylation site in a transmembrane protein provides topological information 588:702 However, phosphorylation and glycosylation are post-translational modifications (PTMs) that occur in a compartment-specific manner and therefore the presence of a phosphorylation or glycosylation site in a transmembrane protein provides topological information. 24225132 6 54 gly glycosylation 1268:1280 arg2 sites 1282:1286 phosphorylation and glycosylation sites 1248:1286 sites 1282:1286 Our method integrates a novel feature in transmembrane protein topology prediction, which results in improved performance for topology prediction and reliable prediction of phosphorylation and glycosylation sites. 24225132 6 55 theme phosphorylation 1248:1262 arg1 sites 1282:1286 phosphorylation and glycosylation sites 1248:1286 sites 1282:1286 Our method integrates a novel feature in transmembrane protein topology prediction, which results in improved performance for topology prediction and reliable prediction of phosphorylation and glycosylation sites. 24225132 4 56 theme transmembrane 790:802 arg1 prediction 821:830 transmembrane protein topology prediction 790:830 transmembrane protein topology prediction 790:830 We examine the combination of phosphorylation and glycosylation site prediction with transmembrane protein topology prediction. 24225132 2 57 from existence 410:418 arg1 loops 396:400 extra-membrane loops 381:400 extra-membrane loops 381:400 Current predictors rely on topogenic signals in the protein sequence, such as the distribution of positively charged residues in extra-membrane loops and the existence of N-terminal signals. 24225132 4 58 theme topology 812:819 arg1 prediction 821:830 transmembrane protein topology prediction 790:830 transmembrane protein topology prediction 790:830 We examine the combination of phosphorylation and glycosylation site prediction with transmembrane protein topology prediction. 24225132 6 59 theme sites 1282:1286 arg1 prediction 1210:1219 topology prediction 1201:1219 topology prediction 1201:1219 Our method integrates a novel feature in transmembrane protein topology prediction, which results in improved performance for topology prediction and reliable prediction of phosphorylation and glycosylation sites. 24225132 6 59 theme sites 1282:1286 arg1 prediction 1234:1243 reliable prediction 1225:1243 reliable prediction 1225:1243 Our method integrates a novel feature in transmembrane protein topology prediction, which results in improved performance for topology prediction and reliable prediction of phosphorylation and glycosylation sites. 24225132 6 60 theme topology 1138:1145 arg1 prediction 1147:1156 transmembrane protein topology prediction 1116:1156 transmembrane protein topology prediction 1116:1156 Our method integrates a novel feature in transmembrane protein topology prediction, which results in improved performance for topology prediction and reliable prediction of phosphorylation and glycosylation sites. 24225132 5 61 theme phosphorylation 996:1010 arg1 topology 924:931 the topology 920:931 the topology of transmembrane proteins 920:957 We report the development of a Hidden Markov Model based method, capable of predicting the topology of transmembrane proteins and the existence of kinase specific phosphorylation and N/O-linked glycosylation sites along the protein sequence. 24225132 5 61 theme phosphorylation 996:1010 arg1 existence 967:975 the existence 963:975 the existence of kinase specific phosphorylation and N/O-linked glycosylation sites along the protein sequence 963:1072 We report the development of a Hidden Markov Model based method, capable of predicting the topology of transmembrane proteins and the existence of kinase specific phosphorylation and N/O-linked glycosylation sites along the protein sequence. 24225132 2 62 theme topogenic 279:287 arg1 distribution 334:345 the distribution 330:345 the distribution of positively charged residues in extra-membrane loops and the existence of N-terminal signals 330:440 Current predictors rely on topogenic signals in the protein sequence, such as the distribution of positively charged residues in extra-membrane loops and the existence of N-terminal signals. 24225132 2 62 theme topogenic 279:287 arg1 signals 289:295 topogenic signals 279:295 topogenic signals 279:295 Current predictors rely on topogenic signals in the protein sequence, such as the distribution of positively charged residues in extra-membrane loops and the existence of N-terminal signals. 24225132 5 63 theme transmembrane 936:948 arg1 proteins 950:957 transmembrane proteins 936:957 transmembrane proteins 936:957 We report the development of a Hidden Markov Model based method, capable of predicting the topology of transmembrane proteins and the existence of kinase specific phosphorylation and N/O-linked glycosylation sites along the protein sequence. 24225132 4 64 theme protein 804:810 arg1 prediction 821:830 transmembrane protein topology prediction 790:830 transmembrane protein topology prediction 790:830 We examine the combination of phosphorylation and glycosylation site prediction with transmembrane protein topology prediction. 24225132 5 65 theme N/O-linked 1016:1025 arg1 sites 1041:1045 kinase specific phosphorylation and N/O-linked glycosylation sites 980:1045 sites 1041:1045 We report the development of a Hidden Markov Model based method, capable of predicting the topology of transmembrane proteins and the existence of kinase specific phosphorylation and N/O-linked glycosylation sites along the protein sequence. 24225132 2 66 theme N-terminal 423:432 arg1 signals 434:440 N-terminal signals 423:440 N-terminal signals 423:440 Current predictors rely on topogenic signals in the protein sequence, such as the distribution of positively charged residues in extra-membrane loops and the existence of N-terminal signals. 24225132 3 67 theme transmembrane 649:661 arg1 protein 663:669 a transmembrane protein 647:669 a transmembrane protein provides topological information 647:702 However, phosphorylation and glycosylation are post-translational modifications (PTMs) that occur in a compartment-specific manner and therefore the presence of a phosphorylation or glycosylation site in a transmembrane protein provides topological information. 24225132 1 68 theme large 147:151 arg1 number 153:158 a large number 145:158 a large number of computational methods 145:183 During the last two decades a large number of computational methods have been developed for predicting transmembrane protein topology. 24225132 5 69 theme proteins 950:957 arg1 topology 924:931 the topology 920:931 the topology of transmembrane proteins 920:957 We report the development of a Hidden Markov Model based method, capable of predicting the topology of transmembrane proteins and the existence of kinase specific phosphorylation and N/O-linked glycosylation sites along the protein sequence. 24225132 5 69 theme proteins 950:957 arg1 existence 967:975 the existence 963:975 the existence of kinase specific phosphorylation and N/O-linked glycosylation sites along the protein sequence 963:1072 We report the development of a Hidden Markov Model based method, capable of predicting the topology of transmembrane proteins and the existence of kinase specific phosphorylation and N/O-linked glycosylation sites along the protein sequence. 24225132 6 70 theme transmembrane 1116:1128 arg1 prediction 1147:1156 transmembrane protein topology prediction 1116:1156 transmembrane protein topology prediction 1116:1156 Our method integrates a novel feature in transmembrane protein topology prediction, which results in improved performance for topology prediction and reliable prediction of phosphorylation and glycosylation sites. 24225132 6 71 theme glycosylation 1268:1280 arg1 sites 1282:1286 phosphorylation and glycosylation sites 1248:1286 sites 1282:1286 Our method integrates a novel feature in transmembrane protein topology prediction, which results in improved performance for topology prediction and reliable prediction of phosphorylation and glycosylation sites. 24225132 2 72 theme extra-membrane 381:394 arg1 loops 396:400 extra-membrane loops 381:400 extra-membrane loops 381:400 Current predictors rely on topogenic signals in the protein sequence, such as the distribution of positively charged residues in extra-membrane loops and the existence of N-terminal signals. 23701548 1 0 link O-linked 112:119 arg1 group 172:176 an O-linked mitochondria-targeting 4-triphenylphosphoniumbutyl group 109:176 an O-linked mitochondria-targeting 4-triphenylphosphoniumbutyl group at either position 3 or position 4' 109:212 Resveratrol derivatives bearing an O-linked mitochondria-targeting 4-triphenylphosphoniumbutyl group at either position 3 or position 4' are prooxidant and cytotoxic for cultured cells, selectively killing fast-growing cells when supplied in the low μM range. 23701548 7 1 theme chemotherapeutic 1328:1343 arg1 agents 1345:1350 chemotherapeutic agents 1328:1350 chemotherapeutic agents 1328:1350 Resveratrol-triphenylphosphonium conjugates may thus represent a new class of chemotherapeutic agents, redox-active "mitocans", whose mechanisms of action and in vivo activity are worthy of further investigation. 23701548 6 2 theme nucleus 1147:1153 arg1 causes 1188:1193 the causes 1184:1193 the causes of ROS generation and of depolarization 1184:1233 Effectiveness is increased if resveratrol hydroxyls are acetylated or methylated; this excludes the involvement of autooxidation of the polyphenolic nucleus and a protonophoric cycle as the causes of ROS generation and of depolarization, respectively. 23701548 6 2 theme nucleus 1147:1153 arg1 involvement 1098:1108 the involvement 1094:1108 the involvement of autooxidation of the polyphenolic nucleus and a protonophoric cycle 1094:1179 Effectiveness is increased if resveratrol hydroxyls are acetylated or methylated; this excludes the involvement of autooxidation of the polyphenolic nucleus and a protonophoric cycle as the causes of ROS generation and of depolarization, respectively. 23701548 4 3 theme compounds 721:729 arg1 accumulation 701:712 accumulation 701:712 accumulation of the compounds into mitochondria 701:747 Cytotoxicity is due to ROS produced upon accumulation of the compounds into mitochondria, and specifically to H2O2, since externally added membrane-permeant catalase largely prevents cell death while superoxide dismutase potentiates toxicity. 23701548 7 4 theme agents 1345:1350 arg1 class 1319:1323 a new class 1313:1323 a new class of chemotherapeutic agents 1313:1350 Resveratrol-triphenylphosphonium conjugates may thus represent a new class of chemotherapeutic agents, redox-active "mitocans", whose mechanisms of action and in vivo activity are worthy of further investigation. 23701548 7 4 theme agents 1345:1350 arg1 " 1375:1375 redox-active "mitocans" 1353:1375 redox-active "mitocans" 1353:1375 Resveratrol-triphenylphosphonium conjugates may thus represent a new class of chemotherapeutic agents, redox-active "mitocans", whose mechanisms of action and in vivo activity are worthy of further investigation. 23701548 3 5 theme /Bak 563:566 arg1 cells 573:577 Bax(-/-)/Bak(-/-) cells 555:577 Bax(-/-)/Bak(-/-) cells 555:577 Experiments with Bax(-/-)/Bak(-/-) cells and a pan-caspase inhibitor show that cell death is mostly of the necrotic type. 23701548 1 6 theme Resveratrol 77:87 arg1 derivatives 89:99 Resveratrol derivatives 77:99 Resveratrol derivatives bearing an O-linked mitochondria-targeting 4-triphenylphosphoniumbutyl group at either position 3 or position 4' 77:212 Resveratrol derivatives bearing an O-linked mitochondria-targeting 4-triphenylphosphoniumbutyl group at either position 3 or position 4' are prooxidant and cytotoxic for cultured cells, selectively killing fast-growing cells when supplied in the low μM range. 23701548 5 7 dep in 976:977 arg1 situ 979:982 situ 979:982 situ 979:982 The mitochondriotropic compounds cause ROS-independent depolarization of in situ mitochondria. 23701548 5 8 theme in 976:977 arg1 mitochondria 984:995 in situ mitochondria 976:995 in situ mitochondria 976:995 The mitochondriotropic compounds cause ROS-independent depolarization of in situ mitochondria. 23701548 6 9 theme generation 1202:1211 arg1 causes 1188:1193 the causes 1184:1193 the causes of ROS generation and of depolarization 1184:1233 Effectiveness is increased if resveratrol hydroxyls are acetylated or methylated; this excludes the involvement of autooxidation of the polyphenolic nucleus and a protonophoric cycle as the causes of ROS generation and of depolarization, respectively. 23701548 6 9 theme generation 1202:1211 arg1 involvement 1098:1108 the involvement 1094:1108 the involvement of autooxidation of the polyphenolic nucleus and a protonophoric cycle 1094:1179 Effectiveness is increased if resveratrol hydroxyls are acetylated or methylated; this excludes the involvement of autooxidation of the polyphenolic nucleus and a protonophoric cycle as the causes of ROS generation and of depolarization, respectively. 23701548 5 10 theme mitochondria 984:995 arg1 depolarization 958:971 ROS-independent depolarization 942:971 ROS-independent depolarization of in situ mitochondria 942:995 The mitochondriotropic compounds cause ROS-independent depolarization of in situ mitochondria. 23701548 1 11 from position 202:209 arg1 group 172:176 an O-linked mitochondria-targeting 4-triphenylphosphoniumbutyl group 109:176 an O-linked mitochondria-targeting 4-triphenylphosphoniumbutyl group at either position 3 or position 4' 109:212 Resveratrol derivatives bearing an O-linked mitochondria-targeting 4-triphenylphosphoniumbutyl group at either position 3 or position 4' are prooxidant and cytotoxic for cultured cells, selectively killing fast-growing cells when supplied in the low μM range. 23701548 4 12 theme membrane-permeant 799:815 arg1 catalase 817:824 externally added membrane-permeant catalase 782:824 externally added membrane-permeant catalase 782:824 Cytotoxicity is due to ROS produced upon accumulation of the compounds into mitochondria, and specifically to H2O2, since externally added membrane-permeant catalase largely prevents cell death while superoxide dismutase potentiates toxicity. 23701548 7 13 theme investigation 1448:1460 arg1 worthy 1430:1435 worthy 1430:1435 worthy of further investigation 1430:1460 Resveratrol-triphenylphosphonium conjugates may thus represent a new class of chemotherapeutic agents, redox-active "mitocans", whose mechanisms of action and in vivo activity are worthy of further investigation. 23701548 7 13 theme investigation 1448:1460 arg1 mechanisms 1384:1393 mechanisms 1384:1393 mechanisms 1384:1393 Resveratrol-triphenylphosphonium conjugates may thus represent a new class of chemotherapeutic agents, redox-active "mitocans", whose mechanisms of action and in vivo activity are worthy of further investigation. 23701548 2 14 theme mitochondriotropic 446:463 arg1 derivatives 465:475 the mitochondriotropic derivatives 442:475 the mitochondriotropic derivatives 442:475 Resveratrol is essentially without effect under these experimental conditions, while the cytotoxicity of the mitochondriotropic derivatives increases if they are methylated on the remaining hydroxyls. 23701548 7 15 theme new 1315:1317 arg1 class 1319:1323 a new class 1313:1323 a new class of chemotherapeutic agents 1313:1350 Resveratrol-triphenylphosphonium conjugates may thus represent a new class of chemotherapeutic agents, redox-active "mitocans", whose mechanisms of action and in vivo activity are worthy of further investigation. 23701548 7 15 theme new 1315:1317 arg1 " 1375:1375 redox-active "mitocans" 1353:1375 redox-active "mitocans" 1353:1375 Resveratrol-triphenylphosphonium conjugates may thus represent a new class of chemotherapeutic agents, redox-active "mitocans", whose mechanisms of action and in vivo activity are worthy of further investigation. 23701548 1 16 from position 188:195 arg1 group 172:176 an O-linked mitochondria-targeting 4-triphenylphosphoniumbutyl group 109:176 an O-linked mitochondria-targeting 4-triphenylphosphoniumbutyl group at either position 3 or position 4' 109:212 Resveratrol derivatives bearing an O-linked mitochondria-targeting 4-triphenylphosphoniumbutyl group at either position 3 or position 4' are prooxidant and cytotoxic for cultured cells, selectively killing fast-growing cells when supplied in the low μM range. 23701548 3 17 with inhibitor 597:605 arg1 cells 573:577 Bax(-/-)/Bak(-/-) cells 555:577 Bax(-/-)/Bak(-/-) cells 555:577 Experiments with Bax(-/-)/Bak(-/-) cells and a pan-caspase inhibitor show that cell death is mostly of the necrotic type. 23701548 6 18 theme cycle 1175:1179 arg1 causes 1188:1193 the causes 1184:1193 the causes of ROS generation and of depolarization 1184:1233 Effectiveness is increased if resveratrol hydroxyls are acetylated or methylated; this excludes the involvement of autooxidation of the polyphenolic nucleus and a protonophoric cycle as the causes of ROS generation and of depolarization, respectively. 23701548 6 18 theme cycle 1175:1179 arg1 involvement 1098:1108 the involvement 1094:1108 the involvement of autooxidation of the polyphenolic nucleus and a protonophoric cycle 1094:1179 Effectiveness is increased if resveratrol hydroxyls are acetylated or methylated; this excludes the involvement of autooxidation of the polyphenolic nucleus and a protonophoric cycle as the causes of ROS generation and of depolarization, respectively. 23701548 0 19 theme resveratrol 22:32 arg1 derivatives 34:44 Mitochondria-targeted resveratrol derivatives 0:44 Mitochondria-targeted resveratrol derivatives 0:44 Mitochondria-targeted resveratrol derivatives act as cytotoxic pro-oxidants. 23701548 0 19 theme resveratrol 22:32 arg1 pro-oxidants 63:74 cytotoxic pro-oxidants 53:74 cytotoxic pro-oxidants 53:74 Mitochondria-targeted resveratrol derivatives act as cytotoxic pro-oxidants. 23701548 1 20 theme O-linked 112:119 arg1 group 172:176 an O-linked mitochondria-targeting 4-triphenylphosphoniumbutyl group 109:176 an O-linked mitochondria-targeting 4-triphenylphosphoniumbutyl group at either position 3 or position 4' 109:212 Resveratrol derivatives bearing an O-linked mitochondria-targeting 4-triphenylphosphoniumbutyl group at either position 3 or position 4' are prooxidant and cytotoxic for cultured cells, selectively killing fast-growing cells when supplied in the low μM range. 23701548 6 21 theme protonophoric 1161:1173 arg1 cycle 1175:1179 a protonophoric cycle 1159:1179 a protonophoric cycle 1159:1179 Effectiveness is increased if resveratrol hydroxyls are acetylated or methylated; this excludes the involvement of autooxidation of the polyphenolic nucleus and a protonophoric cycle as the causes of ROS generation and of depolarization, respectively. 23701548 0 22 theme Mitochondria-targeted 0:20 arg1 derivatives 34:44 Mitochondria-targeted resveratrol derivatives 0:44 Mitochondria-targeted resveratrol derivatives 0:44 Mitochondria-targeted resveratrol derivatives act as cytotoxic pro-oxidants. 23701548 0 22 theme Mitochondria-targeted 0:20 arg1 pro-oxidants 63:74 cytotoxic pro-oxidants 53:74 cytotoxic pro-oxidants 53:74 Mitochondria-targeted resveratrol derivatives act as cytotoxic pro-oxidants. 23701548 1 23 theme low 323:325 arg1 range 330:334 the low μM range 319:334 the low μM range 319:334 Resveratrol derivatives bearing an O-linked mitochondria-targeting 4-triphenylphosphoniumbutyl group at either position 3 or position 4' are prooxidant and cytotoxic for cultured cells, selectively killing fast-growing cells when supplied in the low μM range. 23701548 1 24 theme mitochondria-targeting 121:142 arg1 group 172:176 an O-linked mitochondria-targeting 4-triphenylphosphoniumbutyl group 109:176 an O-linked mitochondria-targeting 4-triphenylphosphoniumbutyl group at either position 3 or position 4' 109:212 Resveratrol derivatives bearing an O-linked mitochondria-targeting 4-triphenylphosphoniumbutyl group at either position 3 or position 4' are prooxidant and cytotoxic for cultured cells, selectively killing fast-growing cells when supplied in the low μM range. 23701548 5 25 theme ROS-independent 942:956 arg1 depolarization 958:971 ROS-independent depolarization 942:971 ROS-independent depolarization of in situ mitochondria 942:995 The mitochondriotropic compounds cause ROS-independent depolarization of in situ mitochondria. 23701548 1 26 theme μM 327:328 arg1 range 330:334 the low μM range 319:334 the low μM range 319:334 Resveratrol derivatives bearing an O-linked mitochondria-targeting 4-triphenylphosphoniumbutyl group at either position 3 or position 4' are prooxidant and cytotoxic for cultured cells, selectively killing fast-growing cells when supplied in the low μM range. 23701548 1 27 theme 4-triphenylphosphoniumbutyl 144:170 arg1 group 172:176 an O-linked mitochondria-targeting 4-triphenylphosphoniumbutyl group 109:176 an O-linked mitochondria-targeting 4-triphenylphosphoniumbutyl group at either position 3 or position 4' 109:212 Resveratrol derivatives bearing an O-linked mitochondria-targeting 4-triphenylphosphoniumbutyl group at either position 3 or position 4' are prooxidant and cytotoxic for cultured cells, selectively killing fast-growing cells when supplied in the low μM range. 23701548 7 28 theme mitocans 1367:1374 arg1 " 1375:1375 redox-active "mitocans" 1353:1375 redox-active "mitocans" 1353:1375 Resveratrol-triphenylphosphonium conjugates may thus represent a new class of chemotherapeutic agents, redox-active "mitocans", whose mechanisms of action and in vivo activity are worthy of further investigation. 23701548 7 28 theme mitocans 1367:1374 arg1 class 1319:1323 a new class 1313:1323 a new class of chemotherapeutic agents 1313:1350 Resveratrol-triphenylphosphonium conjugates may thus represent a new class of chemotherapeutic agents, redox-active "mitocans", whose mechanisms of action and in vivo activity are worthy of further investigation. 23701548 7 29 theme Resveratrol-triphenylphosphonium 1250:1281 arg1 conjugates 1283:1292 Resveratrol-triphenylphosphonium conjugates 1250:1292 Resveratrol-triphenylphosphonium conjugates 1250:1292 Resveratrol-triphenylphosphonium conjugates may thus represent a new class of chemotherapeutic agents, redox-active "mitocans", whose mechanisms of action and in vivo activity are worthy of further investigation. 23701548 1 30 theme cultured 247:254 arg1 cells 256:260 cultured cells 247:260 cultured cells 247:260 Resveratrol derivatives bearing an O-linked mitochondria-targeting 4-triphenylphosphoniumbutyl group at either position 3 or position 4' are prooxidant and cytotoxic for cultured cells, selectively killing fast-growing cells when supplied in the low μM range. 23701548 0 31 theme cytotoxic 53:61 arg1 derivatives 34:44 Mitochondria-targeted resveratrol derivatives 0:44 Mitochondria-targeted resveratrol derivatives 0:44 Mitochondria-targeted resveratrol derivatives act as cytotoxic pro-oxidants. 23701548 0 31 theme cytotoxic 53:61 arg1 pro-oxidants 63:74 cytotoxic pro-oxidants 53:74 cytotoxic pro-oxidants 53:74 Mitochondria-targeted resveratrol derivatives act as cytotoxic pro-oxidants. 23701548 7 32 theme in 1409:1410 arg1 activity 1417:1424 in vivo activity 1409:1424 in vivo activity 1409:1424 Resveratrol-triphenylphosphonium conjugates may thus represent a new class of chemotherapeutic agents, redox-active "mitocans", whose mechanisms of action and in vivo activity are worthy of further investigation. 23701548 6 33 theme polyphenolic 1134:1145 arg1 nucleus 1147:1153 the polyphenolic nucleus 1130:1153 the polyphenolic nucleus 1130:1153 Effectiveness is increased if resveratrol hydroxyls are acetylated or methylated; this excludes the involvement of autooxidation of the polyphenolic nucleus and a protonophoric cycle as the causes of ROS generation and of depolarization, respectively. 23701548 5 34 theme mitochondriotropic 907:924 arg1 compounds 926:934 The mitochondriotropic compounds 903:934 The mitochondriotropic compounds 903:934 The mitochondriotropic compounds cause ROS-independent depolarization of in situ mitochondria. 23701548 3 35 with Experiments 538:548 arg1 cells 573:577 Bax(-/-)/Bak(-/-) cells 555:577 Bax(-/-)/Bak(-/-) cells 555:577 Experiments with Bax(-/-)/Bak(-/-) cells and a pan-caspase inhibitor show that cell death is mostly of the necrotic type. 23701548 2 36 theme derivatives 465:475 arg1 cytotoxicity 426:437 the cytotoxicity 422:437 the cytotoxicity of the mitochondriotropic derivatives 422:475 Resveratrol is essentially without effect under these experimental conditions, while the cytotoxicity of the mitochondriotropic derivatives increases if they are methylated on the remaining hydroxyls. 23701548 6 37 theme resveratrol 1028:1038 arg1 hydroxyls 1040:1048 resveratrol hydroxyls 1028:1048 resveratrol hydroxyls 1028:1048 Effectiveness is increased if resveratrol hydroxyls are acetylated or methylated; this excludes the involvement of autooxidation of the polyphenolic nucleus and a protonophoric cycle as the causes of ROS generation and of depolarization, respectively. 23701548 3 38 theme cell 617:620 arg1 death 622:626 cell death 617:626 cell death 617:626 Experiments with Bax(-/-)/Bak(-/-) cells and a pan-caspase inhibitor show that cell death is mostly of the necrotic type. 23701548 2 39 theme experimental 391:402 arg1 conditions 404:413 these experimental conditions 385:413 these experimental conditions 385:413 Resveratrol is essentially without effect under these experimental conditions, while the cytotoxicity of the mitochondriotropic derivatives increases if they are methylated on the remaining hydroxyls. 23701548 2 40 theme remaining 517:525 arg1 hydroxyls 527:535 the remaining hydroxyls 513:535 the remaining hydroxyls 513:535 Resveratrol is essentially without effect under these experimental conditions, while the cytotoxicity of the mitochondriotropic derivatives increases if they are methylated on the remaining hydroxyls. 23701548 4 41 theme superoxide 860:869 arg1 dismutase 871:879 superoxide dismutase 860:879 superoxide dismutase 860:879 Cytotoxicity is due to ROS produced upon accumulation of the compounds into mitochondria, and specifically to H2O2, since externally added membrane-permeant catalase largely prevents cell death while superoxide dismutase potentiates toxicity. 23701548 7 42 theme action 1398:1403 arg1 mechanisms 1384:1393 mechanisms 1384:1393 mechanisms 1384:1393 Resveratrol-triphenylphosphonium conjugates may thus represent a new class of chemotherapeutic agents, redox-active "mitocans", whose mechanisms of action and in vivo activity are worthy of further investigation. 23701548 7 42 theme action 1398:1403 arg1 worthy 1430:1435 worthy 1430:1435 worthy of further investigation 1430:1460 Resveratrol-triphenylphosphonium conjugates may thus represent a new class of chemotherapeutic agents, redox-active "mitocans", whose mechanisms of action and in vivo activity are worthy of further investigation. 23701548 3 43 theme necrotic 645:652 arg1 type 654:657 the necrotic type 641:657 the necrotic type 641:657 Experiments with Bax(-/-)/Bak(-/-) cells and a pan-caspase inhibitor show that cell death is mostly of the necrotic type. 23701548 3 44 theme pan-caspase 585:595 arg1 inhibitor 597:605 a pan-caspase inhibitor 583:605 a pan-caspase inhibitor 583:605 Experiments with Bax(-/-)/Bak(-/-) cells and a pan-caspase inhibitor show that cell death is mostly of the necrotic type. 23701548 4 45 theme added 793:797 arg1 catalase 817:824 externally added membrane-permeant catalase 782:824 externally added membrane-permeant catalase 782:824 Cytotoxicity is due to ROS produced upon accumulation of the compounds into mitochondria, and specifically to H2O2, since externally added membrane-permeant catalase largely prevents cell death while superoxide dismutase potentiates toxicity. 23701548 7 46 dep in 1409:1410 arg1 vivo 1412:1415 vivo 1412:1415 vivo 1412:1415 Resveratrol-triphenylphosphonium conjugates may thus represent a new class of chemotherapeutic agents, redox-active "mitocans", whose mechanisms of action and in vivo activity are worthy of further investigation. 23701548 3 47 theme Bax 555:557 arg1 cells 573:577 Bax(-/-)/Bak(-/-) cells 555:577 Bax(-/-)/Bak(-/-) cells 555:577 Experiments with Bax(-/-)/Bak(-/-) cells and a pan-caspase inhibitor show that cell death is mostly of the necrotic type. 23701548 6 48 theme depolarization 1220:1233 arg1 causes 1188:1193 the causes 1184:1193 the causes of ROS generation and of depolarization 1184:1233 Effectiveness is increased if resveratrol hydroxyls are acetylated or methylated; this excludes the involvement of autooxidation of the polyphenolic nucleus and a protonophoric cycle as the causes of ROS generation and of depolarization, respectively. 23701548 6 48 theme depolarization 1220:1233 arg1 involvement 1098:1108 the involvement 1094:1108 the involvement of autooxidation of the polyphenolic nucleus and a protonophoric cycle 1094:1179 Effectiveness is increased if resveratrol hydroxyls are acetylated or methylated; this excludes the involvement of autooxidation of the polyphenolic nucleus and a protonophoric cycle as the causes of ROS generation and of depolarization, respectively. 23701548 6 49 theme autooxidation 1113:1125 arg1 causes 1188:1193 the causes 1184:1193 the causes of ROS generation and of depolarization 1184:1233 Effectiveness is increased if resveratrol hydroxyls are acetylated or methylated; this excludes the involvement of autooxidation of the polyphenolic nucleus and a protonophoric cycle as the causes of ROS generation and of depolarization, respectively. 23701548 6 49 theme autooxidation 1113:1125 arg1 involvement 1098:1108 the involvement 1094:1108 the involvement of autooxidation of the polyphenolic nucleus and a protonophoric cycle 1094:1179 Effectiveness is increased if resveratrol hydroxyls are acetylated or methylated; this excludes the involvement of autooxidation of the polyphenolic nucleus and a protonophoric cycle as the causes of ROS generation and of depolarization, respectively. 23701548 7 50 theme activity 1417:1424 arg1 mechanisms 1384:1393 mechanisms 1384:1393 mechanisms 1384:1393 Resveratrol-triphenylphosphonium conjugates may thus represent a new class of chemotherapeutic agents, redox-active "mitocans", whose mechanisms of action and in vivo activity are worthy of further investigation. 23701548 7 50 theme activity 1417:1424 arg1 worthy 1430:1435 worthy 1430:1435 worthy of further investigation 1430:1460 Resveratrol-triphenylphosphonium conjugates may thus represent a new class of chemotherapeutic agents, redox-active "mitocans", whose mechanisms of action and in vivo activity are worthy of further investigation. 23701548 4 51 theme cell 843:846 arg1 death 848:852 cell death 843:852 cell death 843:852 Cytotoxicity is due to ROS produced upon accumulation of the compounds into mitochondria, and specifically to H2O2, since externally added membrane-permeant catalase largely prevents cell death while superoxide dismutase potentiates toxicity. 23701548 6 52 theme ROS 1198:1200 arg1 generation 1202:1211 ROS generation 1198:1211 ROS generation 1198:1211 Effectiveness is increased if resveratrol hydroxyls are acetylated or methylated; this excludes the involvement of autooxidation of the polyphenolic nucleus and a protonophoric cycle as the causes of ROS generation and of depolarization, respectively. 23701548 7 53 theme further 1440:1446 arg1 investigation 1448:1460 further investigation 1440:1460 further investigation 1440:1460 Resveratrol-triphenylphosphonium conjugates may thus represent a new class of chemotherapeutic agents, redox-active "mitocans", whose mechanisms of action and in vivo activity are worthy of further investigation. 23701548 1 54 theme fast-growing 283:294 arg1 cells 296:300 fast-growing cells 283:300 fast-growing cells when supplied in the low μM range 283:334 Resveratrol derivatives bearing an O-linked mitochondria-targeting 4-triphenylphosphoniumbutyl group at either position 3 or position 4' are prooxidant and cytotoxic for cultured cells, selectively killing fast-growing cells when supplied in the low μM range. 23701548 7 55 theme redox-active 1353:1364 arg1 " 1375:1375 redox-active "mitocans" 1353:1375 redox-active "mitocans" 1353:1375 Resveratrol-triphenylphosphonium conjugates may thus represent a new class of chemotherapeutic agents, redox-active "mitocans", whose mechanisms of action and in vivo activity are worthy of further investigation. 23701548 7 55 theme redox-active 1353:1364 arg1 class 1319:1323 a new class 1313:1323 a new class of chemotherapeutic agents 1313:1350 Resveratrol-triphenylphosphonium conjugates may thus represent a new class of chemotherapeutic agents, redox-active "mitocans", whose mechanisms of action and in vivo activity are worthy of further investigation. 23701548 3 56 theme -/- 568:570 arg1 cells 573:577 Bax(-/-)/Bak(-/-) cells 555:577 Bax(-/-)/Bak(-/-) cells 555:577 Experiments with Bax(-/-)/Bak(-/-) cells and a pan-caspase inhibitor show that cell death is mostly of the necrotic type. 28670342 4 0 with stimulation 742:752 arg1 5-ALA 767:771 20 mg/L 5-ALA 759:771 20 mg/L 5-ALA 759:771 RESULTS Both the biomass and the ARA content of P. purpureum were enhanced by stimulation with 20 mg/L 5-ALA, leading to an optimal ARA yield of 170.32 mg/L-a 70.82% increase compared with control conditions. 28670342 1 1 theme valuable 200:207 arg1 proteins 209:216 several valuable proteins 192:216 several valuable proteins 192:216 BACKGROUND The microalga Porphyridium purpureum within Rhodophyta abundantly produces several valuable proteins, polysaccharides, pigments and long-chain polyunsaturated fatty acid; it is especially effective in accumulating arachidonic acid (ARA). 28670342 8 2 theme TAG 1627:1629 arg1 accumulation 1631:1642 TAG accumulation 1627:1642 TAG accumulation 1627:1642 As the levels of the most abundant TAGs increased under 5-ALA promotion and because 78.1 ± 3.4% (by weight) of detected TAG-branched chains contained ARA, the increase of ARA was mainly caused by TAG accumulation. 28670342 8 3 theme TAGs 1466:1469 arg1 levels 1438:1443 the levels 1434:1443 the levels of the most abundant TAGs 1434:1469 As the levels of the most abundant TAGs increased under 5-ALA promotion and because 78.1 ± 3.4% (by weight) of detected TAG-branched chains contained ARA, the increase of ARA was mainly caused by TAG accumulation. 28670342 8 4 theme 5-ALA 1487:1491 arg1 promotion 1493:1501 5-ALA promotion 1487:1501 5-ALA promotion 1487:1501 As the levels of the most abundant TAGs increased under 5-ALA promotion and because 78.1 ± 3.4% (by weight) of detected TAG-branched chains contained ARA, the increase of ARA was mainly caused by TAG accumulation. 28670342 10 5 from microalgae 1962:1971 arg1 bioproducts 1945:1955 bioproducts 1945:1955 bioproducts from microalgae 1945:1971 These results are helpful for understanding the microalgae metabolic pathways affected by phytohormones and for guiding the development of bioproducts from microalgae. 28670342 10 5 from microalgae 1962:1971 arg1 development 1930:1940 the development 1926:1940 the development of bioproducts from microalgae 1926:1971 These results are helpful for understanding the microalgae metabolic pathways affected by phytohormones and for guiding the development of bioproducts from microalgae. 28670342 4 6 theme purpureum 715:723 arg1 biomass 681:687 the biomass 677:687 the biomass 677:687 RESULTS Both the biomass and the ARA content of P. purpureum were enhanced by stimulation with 20 mg/L 5-ALA, leading to an optimal ARA yield of 170.32 mg/L-a 70.82% increase compared with control conditions. 28670342 4 6 theme purpureum 715:723 arg1 content 701:707 the ARA content 693:707 the ARA content of P. purpureum 693:723 RESULTS Both the biomass and the ARA content of P. purpureum were enhanced by stimulation with 20 mg/L 5-ALA, leading to an optimal ARA yield of 170.32 mg/L-a 70.82% increase compared with control conditions. 28670342 6 7 theme total 998:1002 arg1 lipids 990:995 total lipids 984:995 total lipids 984:995 Based on variations in the fatty acid composition, total lipids, total proteins, total carbohydrates and pigment content during the cultivation period, we propose that the accumulation of ARA stimulated by 5-ALA occurs at the expense of other UFAs and total proteins, which may be related to decreased zeaxanthin. 28670342 6 7 theme total 998:1002 arg1 proteins 1004:1011 total proteins 998:1011 total proteins 998:1011 Based on variations in the fatty acid composition, total lipids, total proteins, total carbohydrates and pigment content during the cultivation period, we propose that the accumulation of ARA stimulated by 5-ALA occurs at the expense of other UFAs and total proteins, which may be related to decreased zeaxanthin. 28670342 7 8 theme lipids 1346:1351 arg1 lipids 1346:1351 all detected lipids 1333:1351 all detected lipids 1333:1351 Lipidomic analysis revealed that triacylglycerols (TAGs) accounted for 47.5 ± 3.6% of all detected lipids, followed by phosphatidylglycerol (PG) and digalactosyldiacylglycerol (DGDG). 28670342 7 8 theme lipids 1346:1351 arg1 % 1328:1328 47.5 ± 3.6% 1318:1328 47.5 ± 3.6% of all detected lipids 1318:1351 Lipidomic analysis revealed that triacylglycerols (TAGs) accounted for 47.5 ± 3.6% of all detected lipids, followed by phosphatidylglycerol (PG) and digalactosyldiacylglycerol (DGDG). 28670342 10 9 from development 1930:1940 arg1 microalgae 1962:1971 microalgae 1962:1971 microalgae 1962:1971 These results are helpful for understanding the microalgae metabolic pathways affected by phytohormones and for guiding the development of bioproducts from microalgae. 28670342 6 10 theme UFAs 1176:1179 arg1 expense 1159:1165 the expense 1155:1165 the expense 1155:1165 Based on variations in the fatty acid composition, total lipids, total proteins, total carbohydrates and pigment content during the cultivation period, we propose that the accumulation of ARA stimulated by 5-ALA occurs at the expense of other UFAs and total proteins, which may be related to decreased zeaxanthin. 28670342 6 10 theme UFAs 1176:1179 arg1 related 1214:1220 related 1214:1220 related 1214:1220 Based on variations in the fatty acid composition, total lipids, total proteins, total carbohydrates and pigment content during the cultivation period, we propose that the accumulation of ARA stimulated by 5-ALA occurs at the expense of other UFAs and total proteins, which may be related to decreased zeaxanthin. 28670342 8 11 theme ARA 1602:1604 arg1 increase 1590:1597 the increase 1586:1597 the increase of ARA 1586:1604 As the levels of the most abundant TAGs increased under 5-ALA promotion and because 78.1 ± 3.4% (by weight) of detected TAG-branched chains contained ARA, the increase of ARA was mainly caused by TAG accumulation. 28670342 7 12 theme Lipidomic 1247:1255 arg1 analysis 1257:1264 Lipidomic analysis 1247:1264 Lipidomic analysis 1247:1264 Lipidomic analysis revealed that triacylglycerols (TAGs) accounted for 47.5 ± 3.6% of all detected lipids, followed by phosphatidylglycerol (PG) and digalactosyldiacylglycerol (DGDG). 28670342 6 13 theme other 1170:1174 arg1 UFAs 1176:1179 other UFAs 1170:1179 other UFAs 1170:1179 Based on variations in the fatty acid composition, total lipids, total proteins, total carbohydrates and pigment content during the cultivation period, we propose that the accumulation of ARA stimulated by 5-ALA occurs at the expense of other UFAs and total proteins, which may be related to decreased zeaxanthin. 28670342 8 14 theme detected 1542:1549 arg1 chains 1564:1569 detected TAG-branched chains 1542:1569 detected TAG-branched chains 1542:1569 As the levels of the most abundant TAGs increased under 5-ALA promotion and because 78.1 ± 3.4% (by weight) of detected TAG-branched chains contained ARA, the increase of ARA was mainly caused by TAG accumulation. 28670342 5 15 theme ARA 878:880 arg1 yield 882:886 This ARA yield 873:886 This ARA yield 873:886 This ARA yield is the highest ever reported for microalgae. 28670342 5 15 theme ARA 878:880 arg1 highest 895:901 highest 895:901 highest 895:901 This ARA yield is the highest ever reported for microalgae. 28670342 4 16 theme ARA 796:798 arg1 yield 800:804 an optimal ARA yield 785:804 an optimal ARA yield of 170.32 mg/L-a 70.82% increase compared with control conditions 785:870 RESULTS Both the biomass and the ARA content of P. purpureum were enhanced by stimulation with 20 mg/L 5-ALA, leading to an optimal ARA yield of 170.32 mg/L-a 70.82% increase compared with control conditions. 28670342 2 17 theme cell 434:437 arg1 growth 439:444 cell growth 434:444 cell growth 434:444 However, this high ARA yield is always achieved in conditions unfavourable for cell growth. 28670342 0 18 from biosynthesis 48:59 arg1 microalga 72:80 the red microalga 64:80 the red microalga 64:80 5-Aminolevulinic acid promotes arachidonic acid biosynthesis in the red microalga Porphyridium purpureum. 28670342 4 19 theme control 853:859 arg1 conditions 861:870 control conditions 853:870 control conditions 853:870 RESULTS Both the biomass and the ARA content of P. purpureum were enhanced by stimulation with 20 mg/L 5-ALA, leading to an optimal ARA yield of 170.32 mg/L-a 70.82% increase compared with control conditions. 28670342 3 20 attach present 465:471 arg1 study 455:459 this study 450:459 this study 450:459 In this study, we present a method for obtaining desirable ARA levels from P. purpureum while simultaneously promoting cell growth using appropriate concentrations of the growth hormone 5-Aminolevulinic acid (5-ALA). 28670342 3 20 attach present 465:471 arg2 we 462:463 we 462:463 we 462:463 In this study, we present a method for obtaining desirable ARA levels from P. purpureum while simultaneously promoting cell growth using appropriate concentrations of the growth hormone 5-Aminolevulinic acid (5-ALA). 28670342 3 21 theme cell 566:569 arg1 growth 571:576 cell growth 566:576 cell growth 566:576 In this study, we present a method for obtaining desirable ARA levels from P. purpureum while simultaneously promoting cell growth using appropriate concentrations of the growth hormone 5-Aminolevulinic acid (5-ALA). 28670342 10 22 theme bioproducts 1945:1955 arg1 development 1930:1940 the development 1926:1940 the development of bioproducts from microalgae 1926:1971 These results are helpful for understanding the microalgae metabolic pathways affected by phytohormones and for guiding the development of bioproducts from microalgae. 28670342 9 23 theme biomass 1728:1734 arg1 yield 1744:1748 both biomass and ARA yield 1723:1748 both biomass and ARA yield in P. purpureum 1723:1764 CONCLUSIONS This work demonstrated a simple and effective strategy to promote both biomass and ARA yield in P. purpureum by introducing a small amount of 5-ALA. 28670342 6 24 theme decreased 1225:1233 arg1 zeaxanthin 1235:1244 decreased zeaxanthin 1225:1244 decreased zeaxanthin 1225:1244 Based on variations in the fatty acid composition, total lipids, total proteins, total carbohydrates and pigment content during the cultivation period, we propose that the accumulation of ARA stimulated by 5-ALA occurs at the expense of other UFAs and total proteins, which may be related to decreased zeaxanthin. 28670342 6 25 theme total 984:988 arg1 lipids 990:995 total lipids 984:995 total lipids 984:995 Based on variations in the fatty acid composition, total lipids, total proteins, total carbohydrates and pigment content during the cultivation period, we propose that the accumulation of ARA stimulated by 5-ALA occurs at the expense of other UFAs and total proteins, which may be related to decreased zeaxanthin. 28670342 6 25 theme total 984:988 arg1 proteins 1004:1011 total proteins 998:1011 total proteins 998:1011 Based on variations in the fatty acid composition, total lipids, total proteins, total carbohydrates and pigment content during the cultivation period, we propose that the accumulation of ARA stimulated by 5-ALA occurs at the expense of other UFAs and total proteins, which may be related to decreased zeaxanthin. 28670342 6 25 theme total 984:988 arg1 carbohydrates 1020:1032 total carbohydrates 1014:1032 total carbohydrates 1014:1032 Based on variations in the fatty acid composition, total lipids, total proteins, total carbohydrates and pigment content during the cultivation period, we propose that the accumulation of ARA stimulated by 5-ALA occurs at the expense of other UFAs and total proteins, which may be related to decreased zeaxanthin. 28670342 2 26 theme unfavourable 417:428 arg1 conditions 406:415 conditions 406:415 conditions unfavourable for cell growth 406:444 However, this high ARA yield is always achieved in conditions unfavourable for cell growth. 28670342 0 27 theme 5-Aminolevulinic 0:15 arg1 acid 17:20 5-Aminolevulinic acid 0:20 5-Aminolevulinic acid 0:20 5-Aminolevulinic acid promotes arachidonic acid biosynthesis in the red microalga Porphyridium purpureum. 28670342 1 28 theme arachidonic 331:341 arg1 ARA 349:351 ARA 349:351 ARA 349:351 BACKGROUND The microalga Porphyridium purpureum within Rhodophyta abundantly produces several valuable proteins, polysaccharides, pigments and long-chain polyunsaturated fatty acid; it is especially effective in accumulating arachidonic acid (ARA). 28670342 1 28 theme arachidonic 331:341 arg1 acid 343:346 arachidonic acid 331:346 arachidonic acid (ARA) 331:352 BACKGROUND The microalga Porphyridium purpureum within Rhodophyta abundantly produces several valuable proteins, polysaccharides, pigments and long-chain polyunsaturated fatty acid; it is especially effective in accumulating arachidonic acid (ARA). 28670342 1 29 theme BACKGROUND 106:115 arg1 purpureum 144:152 BACKGROUND The microalga Porphyridium purpureum 106:152 BACKGROUND The microalga Porphyridium purpureum within Rhodophyta 106:170 BACKGROUND The microalga Porphyridium purpureum within Rhodophyta abundantly produces several valuable proteins, polysaccharides, pigments and long-chain polyunsaturated fatty acid; it is especially effective in accumulating arachidonic acid (ARA). 28670342 4 30 theme ARA 697:699 arg1 content 701:707 the ARA content 693:707 the ARA content of P. purpureum 693:723 RESULTS Both the biomass and the ARA content of P. purpureum were enhanced by stimulation with 20 mg/L 5-ALA, leading to an optimal ARA yield of 170.32 mg/L-a 70.82% increase compared with control conditions. 28670342 0 31 theme arachidonic 31:41 arg1 biosynthesis 48:59 arachidonic acid biosynthesis 31:59 arachidonic acid biosynthesis in the red microalga 31:80 5-Aminolevulinic acid promotes arachidonic acid biosynthesis in the red microalga Porphyridium purpureum. 28670342 4 32 dep RESULTS 664:670 arg1 enhanced 730:737 enhanced 730:737 enhanced 730:737 RESULTS Both the biomass and the ARA content of P. purpureum were enhanced by stimulation with 20 mg/L 5-ALA, leading to an optimal ARA yield of 170.32 mg/L-a 70.82% increase compared with control conditions. 28670342 1 33 theme The microalga 117:129 arg1 purpureum 144:152 BACKGROUND The microalga Porphyridium purpureum 106:152 BACKGROUND The microalga Porphyridium purpureum within Rhodophyta 106:170 BACKGROUND The microalga Porphyridium purpureum within Rhodophyta abundantly produces several valuable proteins, polysaccharides, pigments and long-chain polyunsaturated fatty acid; it is especially effective in accumulating arachidonic acid (ARA). 28670342 4 34 theme increase 830:837 arg1 yield 800:804 an optimal ARA yield 785:804 an optimal ARA yield of 170.32 mg/L-a 70.82% increase compared with control conditions 785:870 RESULTS Both the biomass and the ARA content of P. purpureum were enhanced by stimulation with 20 mg/L 5-ALA, leading to an optimal ARA yield of 170.32 mg/L-a 70.82% increase compared with control conditions. 28670342 4 35 theme 20 mg/L 759:765 arg1 5-ALA 767:771 20 mg/L 5-ALA 759:771 20 mg/L 5-ALA 759:771 RESULTS Both the biomass and the ARA content of P. purpureum were enhanced by stimulation with 20 mg/L 5-ALA, leading to an optimal ARA yield of 170.32 mg/L-a 70.82% increase compared with control conditions. 28670342 9 36 from yield 1744:1748 arg1 purpureum 1756:1764 P. purpureum 1753:1764 P. purpureum 1753:1764 CONCLUSIONS This work demonstrated a simple and effective strategy to promote both biomass and ARA yield in P. purpureum by introducing a small amount of 5-ALA. 28670342 1 37 theme Porphyridium 131:142 arg1 purpureum 144:152 BACKGROUND The microalga Porphyridium purpureum 106:152 BACKGROUND The microalga Porphyridium purpureum within Rhodophyta 106:170 BACKGROUND The microalga Porphyridium purpureum within Rhodophyta abundantly produces several valuable proteins, polysaccharides, pigments and long-chain polyunsaturated fatty acid; it is especially effective in accumulating arachidonic acid (ARA). 28670342 1 38 theme long-chain 249:258 arg1 acid 282:285 long-chain polyunsaturated fatty acid 249:285 long-chain polyunsaturated fatty acid 249:285 BACKGROUND The microalga Porphyridium purpureum within Rhodophyta abundantly produces several valuable proteins, polysaccharides, pigments and long-chain polyunsaturated fatty acid; it is especially effective in accumulating arachidonic acid (ARA). 28670342 10 39 theme microalgae 1854:1863 arg1 pathways 1875:1882 the microalgae metabolic pathways 1850:1882 the microalgae metabolic pathways affected by phytohormones 1850:1908 These results are helpful for understanding the microalgae metabolic pathways affected by phytohormones and for guiding the development of bioproducts from microalgae. 28670342 6 40 theme acid 966:969 arg1 composition 971:981 the fatty acid composition 956:981 the fatty acid composition 956:981 Based on variations in the fatty acid composition, total lipids, total proteins, total carbohydrates and pigment content during the cultivation period, we propose that the accumulation of ARA stimulated by 5-ALA occurs at the expense of other UFAs and total proteins, which may be related to decreased zeaxanthin. 28670342 3 41 theme 5-Aminolevulinic 633:648 arg1 5-ALA 656:660 5-ALA 656:660 5-ALA 656:660 In this study, we present a method for obtaining desirable ARA levels from P. purpureum while simultaneously promoting cell growth using appropriate concentrations of the growth hormone 5-Aminolevulinic acid (5-ALA). 28670342 3 41 theme 5-Aminolevulinic 633:648 arg1 acid 650:653 the growth hormone 5-Aminolevulinic acid 614:653 the growth hormone 5-Aminolevulinic acid (5-ALA) 614:661 In this study, we present a method for obtaining desirable ARA levels from P. purpureum while simultaneously promoting cell growth using appropriate concentrations of the growth hormone 5-Aminolevulinic acid (5-ALA). 28670342 6 42 theme cultivation 1065:1075 arg1 period 1077:1082 the cultivation period 1061:1082 the cultivation period 1061:1082 Based on variations in the fatty acid composition, total lipids, total proteins, total carbohydrates and pigment content during the cultivation period, we propose that the accumulation of ARA stimulated by 5-ALA occurs at the expense of other UFAs and total proteins, which may be related to decreased zeaxanthin. 28670342 1 43 theme polyunsaturated 260:274 arg1 acid 282:285 long-chain polyunsaturated fatty acid 249:285 long-chain polyunsaturated fatty acid 249:285 BACKGROUND The microalga Porphyridium purpureum within Rhodophyta abundantly produces several valuable proteins, polysaccharides, pigments and long-chain polyunsaturated fatty acid; it is especially effective in accumulating arachidonic acid (ARA). 28670342 0 44 theme acid 43:46 arg1 biosynthesis 48:59 arachidonic acid biosynthesis 31:59 arachidonic acid biosynthesis in the red microalga 31:80 5-Aminolevulinic acid promotes arachidonic acid biosynthesis in the red microalga Porphyridium purpureum. 28670342 6 45 theme fatty 960:964 arg1 composition 971:981 the fatty acid composition 956:981 the fatty acid composition 956:981 Based on variations in the fatty acid composition, total lipids, total proteins, total carbohydrates and pigment content during the cultivation period, we propose that the accumulation of ARA stimulated by 5-ALA occurs at the expense of other UFAs and total proteins, which may be related to decreased zeaxanthin. 28670342 9 46 theme small 1783:1787 arg1 5-ALA 1799:1803 5-ALA 1799:1803 5-ALA 1799:1803 CONCLUSIONS This work demonstrated a simple and effective strategy to promote both biomass and ARA yield in P. purpureum by introducing a small amount of 5-ALA. 28670342 9 46 theme small 1783:1787 arg1 amount 1789:1794 a small amount 1781:1794 a small amount of 5-ALA 1781:1803 CONCLUSIONS This work demonstrated a simple and effective strategy to promote both biomass and ARA yield in P. purpureum by introducing a small amount of 5-ALA. 28670342 3 47 theme acid 650:653 arg1 concentrations 596:609 appropriate concentrations 584:609 appropriate concentrations of the growth hormone 5-Aminolevulinic acid (5-ALA) 584:661 In this study, we present a method for obtaining desirable ARA levels from P. purpureum while simultaneously promoting cell growth using appropriate concentrations of the growth hormone 5-Aminolevulinic acid (5-ALA). 28670342 1 48 theme fatty 276:280 arg1 acid 282:285 long-chain polyunsaturated fatty acid 249:285 long-chain polyunsaturated fatty acid 249:285 BACKGROUND The microalga Porphyridium purpureum within Rhodophyta abundantly produces several valuable proteins, polysaccharides, pigments and long-chain polyunsaturated fatty acid; it is especially effective in accumulating arachidonic acid (ARA). 28670342 9 49 theme simple 1682:1687 arg1 strategy 1703:1710 a simple and effective strategy 1680:1710 a simple and effective strategy to promote both biomass and ARA yield in P. purpureum by introducing a small amount of 5-ALA 1680:1803 CONCLUSIONS This work demonstrated a simple and effective strategy to promote both biomass and ARA yield in P. purpureum by introducing a small amount of 5-ALA. 28670342 3 50 theme growth 618:623 arg1 5-ALA 656:660 5-ALA 656:660 5-ALA 656:660 In this study, we present a method for obtaining desirable ARA levels from P. purpureum while simultaneously promoting cell growth using appropriate concentrations of the growth hormone 5-Aminolevulinic acid (5-ALA). 28670342 3 50 theme growth 618:623 arg1 acid 650:653 the growth hormone 5-Aminolevulinic acid 614:653 the growth hormone 5-Aminolevulinic acid (5-ALA) 614:661 In this study, we present a method for obtaining desirable ARA levels from P. purpureum while simultaneously promoting cell growth using appropriate concentrations of the growth hormone 5-Aminolevulinic acid (5-ALA). 28670342 6 51 theme ARA 1121:1123 arg1 accumulation 1105:1116 the accumulation 1101:1116 the accumulation of ARA stimulated by 5-ALA 1101:1143 Based on variations in the fatty acid composition, total lipids, total proteins, total carbohydrates and pigment content during the cultivation period, we propose that the accumulation of ARA stimulated by 5-ALA occurs at the expense of other UFAs and total proteins, which may be related to decreased zeaxanthin. 28670342 8 52 theme chains 1564:1569 arg1 % 1525:1525 78.1 ± 3.4% 1515:1525 78.1 ± 3.4% (by weight) of detected TAG-branched chains 1515:1569 As the levels of the most abundant TAGs increased under 5-ALA promotion and because 78.1 ± 3.4% (by weight) of detected TAG-branched chains contained ARA, the increase of ARA was mainly caused by TAG accumulation. 28670342 8 52 theme chains 1564:1569 arg1 chains 1564:1569 detected TAG-branched chains 1542:1569 detected TAG-branched chains 1542:1569 As the levels of the most abundant TAGs increased under 5-ALA promotion and because 78.1 ± 3.4% (by weight) of detected TAG-branched chains contained ARA, the increase of ARA was mainly caused by TAG accumulation. 28670342 8 53 theme TAG-branched 1551:1562 arg1 chains 1564:1569 detected TAG-branched chains 1542:1569 detected TAG-branched chains 1542:1569 As the levels of the most abundant TAGs increased under 5-ALA promotion and because 78.1 ± 3.4% (by weight) of detected TAG-branched chains contained ARA, the increase of ARA was mainly caused by TAG accumulation. 28670342 6 54 from variations 942:951 arg1 composition 971:981 the fatty acid composition 956:981 the fatty acid composition 956:981 Based on variations in the fatty acid composition, total lipids, total proteins, total carbohydrates and pigment content during the cultivation period, we propose that the accumulation of ARA stimulated by 5-ALA occurs at the expense of other UFAs and total proteins, which may be related to decreased zeaxanthin. 28670342 6 54 from variations 942:951 arg1 lipids 990:995 total lipids 984:995 total lipids 984:995 Based on variations in the fatty acid composition, total lipids, total proteins, total carbohydrates and pigment content during the cultivation period, we propose that the accumulation of ARA stimulated by 5-ALA occurs at the expense of other UFAs and total proteins, which may be related to decreased zeaxanthin. 28670342 6 54 from variations 942:951 arg1 proteins 1004:1011 total proteins 998:1011 total proteins 998:1011 Based on variations in the fatty acid composition, total lipids, total proteins, total carbohydrates and pigment content during the cultivation period, we propose that the accumulation of ARA stimulated by 5-ALA occurs at the expense of other UFAs and total proteins, which may be related to decreased zeaxanthin. 28670342 6 54 from variations 942:951 arg1 carbohydrates 1020:1032 total carbohydrates 1014:1032 total carbohydrates 1014:1032 Based on variations in the fatty acid composition, total lipids, total proteins, total carbohydrates and pigment content during the cultivation period, we propose that the accumulation of ARA stimulated by 5-ALA occurs at the expense of other UFAs and total proteins, which may be related to decreased zeaxanthin. 28670342 6 54 from variations 942:951 arg1 content 1046:1052 pigment content 1038:1052 pigment content during the cultivation period 1038:1082 Based on variations in the fatty acid composition, total lipids, total proteins, total carbohydrates and pigment content during the cultivation period, we propose that the accumulation of ARA stimulated by 5-ALA occurs at the expense of other UFAs and total proteins, which may be related to decreased zeaxanthin. 28670342 3 55 theme hormone 625:631 arg1 5-ALA 656:660 5-ALA 656:660 5-ALA 656:660 In this study, we present a method for obtaining desirable ARA levels from P. purpureum while simultaneously promoting cell growth using appropriate concentrations of the growth hormone 5-Aminolevulinic acid (5-ALA). 28670342 3 55 theme hormone 625:631 arg1 acid 650:653 the growth hormone 5-Aminolevulinic acid 614:653 the growth hormone 5-Aminolevulinic acid (5-ALA) 614:661 In this study, we present a method for obtaining desirable ARA levels from P. purpureum while simultaneously promoting cell growth using appropriate concentrations of the growth hormone 5-Aminolevulinic acid (5-ALA). 28670342 7 56 dep accounted 1304:1312 arg1 followed 1354:1361 followed 1354:1361 followed by phosphatidylglycerol (PG) and digalactosyldiacylglycerol (DGDG) 1354:1428 Lipidomic analysis revealed that triacylglycerols (TAGs) accounted for 47.5 ± 3.6% of all detected lipids, followed by phosphatidylglycerol (PG) and digalactosyldiacylglycerol (DGDG). 28670342 2 57 theme ARA 374:376 arg1 yield 378:382 this high ARA yield 364:382 this high ARA yield 364:382 However, this high ARA yield is always achieved in conditions unfavourable for cell growth. 28670342 9 58 theme 5-ALA 1799:1803 arg1 5-ALA 1799:1803 5-ALA 1799:1803 5-ALA 1799:1803 CONCLUSIONS This work demonstrated a simple and effective strategy to promote both biomass and ARA yield in P. purpureum by introducing a small amount of 5-ALA. 28670342 9 58 theme 5-ALA 1799:1803 arg1 amount 1789:1794 a small amount 1781:1794 a small amount of 5-ALA 1781:1803 CONCLUSIONS This work demonstrated a simple and effective strategy to promote both biomass and ARA yield in P. purpureum by introducing a small amount of 5-ALA. 28670342 8 59 contain contained 1571:1579 arg1 % 1525:1525 78.1 ± 3.4% 1515:1525 78.1 ± 3.4% (by weight) of detected TAG-branched chains 1515:1569 As the levels of the most abundant TAGs increased under 5-ALA promotion and because 78.1 ± 3.4% (by weight) of detected TAG-branched chains contained ARA, the increase of ARA was mainly caused by TAG accumulation. 28670342 8 59 contain contained 1571:1579 arg1 chains 1564:1569 detected TAG-branched chains 1542:1569 detected TAG-branched chains 1542:1569 As the levels of the most abundant TAGs increased under 5-ALA promotion and because 78.1 ± 3.4% (by weight) of detected TAG-branched chains contained ARA, the increase of ARA was mainly caused by TAG accumulation. 28670342 8 59 contain contained 1571:1579 arg2 ARA 1581:1583 ARA 1581:1583 ARA 1581:1583 As the levels of the most abundant TAGs increased under 5-ALA promotion and because 78.1 ± 3.4% (by weight) of detected TAG-branched chains contained ARA, the increase of ARA was mainly caused by TAG accumulation. 28670342 9 60 theme effective 1693:1701 arg1 strategy 1703:1710 a simple and effective strategy 1680:1710 a simple and effective strategy to promote both biomass and ARA yield in P. purpureum by introducing a small amount of 5-ALA 1680:1803 CONCLUSIONS This work demonstrated a simple and effective strategy to promote both biomass and ARA yield in P. purpureum by introducing a small amount of 5-ALA. 28670342 7 61 theme detected 1337:1344 arg1 lipids 1346:1351 all detected lipids 1333:1351 all detected lipids 1333:1351 Lipidomic analysis revealed that triacylglycerols (TAGs) accounted for 47.5 ± 3.6% of all detected lipids, followed by phosphatidylglycerol (PG) and digalactosyldiacylglycerol (DGDG). 28670342 4 62 theme % 828:828 arg1 increase 830:837 170.32 mg/L-a 70.82% increase 809:837 170.32 mg/L-a 70.82% increase compared with control conditions 809:870 RESULTS Both the biomass and the ARA content of P. purpureum were enhanced by stimulation with 20 mg/L 5-ALA, leading to an optimal ARA yield of 170.32 mg/L-a 70.82% increase compared with control conditions. 28670342 2 63 theme high 369:372 arg1 yield 378:382 this high ARA yield 364:382 this high ARA yield 364:382 However, this high ARA yield is always achieved in conditions unfavourable for cell growth. 28670342 3 64 theme appropriate 584:594 arg1 concentrations 596:609 appropriate concentrations 584:609 appropriate concentrations of the growth hormone 5-Aminolevulinic acid (5-ALA) 584:661 In this study, we present a method for obtaining desirable ARA levels from P. purpureum while simultaneously promoting cell growth using appropriate concentrations of the growth hormone 5-Aminolevulinic acid (5-ALA). 28670342 10 65 dep helpful 1824:1830 arg1 guiding 1918:1924 guiding 1918:1924 guiding the development of bioproducts from microalgae 1918:1971 These results are helpful for understanding the microalgae metabolic pathways affected by phytohormones and for guiding the development of bioproducts from microalgae. 28670342 10 65 dep helpful 1824:1830 arg1 understanding 1836:1848 understanding 1836:1848 understanding the microalgae metabolic pathways affected by phytohormones 1836:1908 These results are helpful for understanding the microalgae metabolic pathways affected by phytohormones and for guiding the development of bioproducts from microalgae. 28670342 4 66 theme optimal 788:794 arg1 yield 800:804 an optimal ARA yield 785:804 an optimal ARA yield of 170.32 mg/L-a 70.82% increase compared with control conditions 785:870 RESULTS Both the biomass and the ARA content of P. purpureum were enhanced by stimulation with 20 mg/L 5-ALA, leading to an optimal ARA yield of 170.32 mg/L-a 70.82% increase compared with control conditions. 28670342 8 67 theme abundant 1457:1464 arg1 TAGs 1466:1469 the most abundant TAGs 1448:1469 the most abundant TAGs 1448:1469 As the levels of the most abundant TAGs increased under 5-ALA promotion and because 78.1 ± 3.4% (by weight) of detected TAG-branched chains contained ARA, the increase of ARA was mainly caused by TAG accumulation. 28670342 6 68 theme proteins 1191:1198 arg1 expense 1159:1165 the expense 1155:1165 the expense 1155:1165 Based on variations in the fatty acid composition, total lipids, total proteins, total carbohydrates and pigment content during the cultivation period, we propose that the accumulation of ARA stimulated by 5-ALA occurs at the expense of other UFAs and total proteins, which may be related to decreased zeaxanthin. 28670342 6 68 theme proteins 1191:1198 arg1 related 1214:1220 related 1214:1220 related 1214:1220 Based on variations in the fatty acid composition, total lipids, total proteins, total carbohydrates and pigment content during the cultivation period, we propose that the accumulation of ARA stimulated by 5-ALA occurs at the expense of other UFAs and total proteins, which may be related to decreased zeaxanthin. 28670342 3 69 theme ARA 506:508 arg1 levels 510:515 desirable ARA levels 496:515 desirable ARA levels 496:515 In this study, we present a method for obtaining desirable ARA levels from P. purpureum while simultaneously promoting cell growth using appropriate concentrations of the growth hormone 5-Aminolevulinic acid (5-ALA). 28670342 3 70 theme desirable 496:504 arg1 levels 510:515 desirable ARA levels 496:515 desirable ARA levels 496:515 In this study, we present a method for obtaining desirable ARA levels from P. purpureum while simultaneously promoting cell growth using appropriate concentrations of the growth hormone 5-Aminolevulinic acid (5-ALA). 28670342 6 71 theme pigment 1038:1044 arg1 content 1046:1052 pigment content 1038:1052 pigment content during the cultivation period 1038:1082 Based on variations in the fatty acid composition, total lipids, total proteins, total carbohydrates and pigment content during the cultivation period, we propose that the accumulation of ARA stimulated by 5-ALA occurs at the expense of other UFAs and total proteins, which may be related to decreased zeaxanthin. 28670342 6 72 theme total 1185:1189 arg1 proteins 1191:1198 total proteins 1185:1198 total proteins 1185:1198 Based on variations in the fatty acid composition, total lipids, total proteins, total carbohydrates and pigment content during the cultivation period, we propose that the accumulation of ARA stimulated by 5-ALA occurs at the expense of other UFAs and total proteins, which may be related to decreased zeaxanthin. 28670342 9 73 dep CONCLUSIONS 1645:1655 arg1 demonstrated 1667:1678 demonstrated 1667:1678 demonstrated a simple and effective strategy to promote both biomass and ARA yield in P. purpureum by introducing a small amount of 5-ALA 1667:1803 CONCLUSIONS This work demonstrated a simple and effective strategy to promote both biomass and ARA yield in P. purpureum by introducing a small amount of 5-ALA. 28670342 6 74 theme total 1014:1018 arg1 lipids 990:995 total lipids 984:995 total lipids 984:995 Based on variations in the fatty acid composition, total lipids, total proteins, total carbohydrates and pigment content during the cultivation period, we propose that the accumulation of ARA stimulated by 5-ALA occurs at the expense of other UFAs and total proteins, which may be related to decreased zeaxanthin. 28670342 6 74 theme total 1014:1018 arg1 carbohydrates 1020:1032 total carbohydrates 1014:1032 total carbohydrates 1014:1032 Based on variations in the fatty acid composition, total lipids, total proteins, total carbohydrates and pigment content during the cultivation period, we propose that the accumulation of ARA stimulated by 5-ALA occurs at the expense of other UFAs and total proteins, which may be related to decreased zeaxanthin. 28670342 0 75 theme red 68:70 arg1 microalga 72:80 the red microalga 64:80 the red microalga 64:80 5-Aminolevulinic acid promotes arachidonic acid biosynthesis in the red microalga Porphyridium purpureum. 28670342 10 76 theme metabolic 1865:1873 arg1 pathways 1875:1882 the microalgae metabolic pathways 1850:1882 the microalgae metabolic pathways affected by phytohormones 1850:1908 These results are helpful for understanding the microalgae metabolic pathways affected by phytohormones and for guiding the development of bioproducts from microalgae. 28670342 4 77 theme 170.32 mg/L-a 809:821 arg1 increase 830:837 170.32 mg/L-a 70.82% increase 809:837 170.32 mg/L-a 70.82% increase compared with control conditions 809:870 RESULTS Both the biomass and the ARA content of P. purpureum were enhanced by stimulation with 20 mg/L 5-ALA, leading to an optimal ARA yield of 170.32 mg/L-a 70.82% increase compared with control conditions. 28670342 1 78 theme several 192:198 arg1 proteins 209:216 several valuable proteins 192:216 several valuable proteins 192:216 BACKGROUND The microalga Porphyridium purpureum within Rhodophyta abundantly produces several valuable proteins, polysaccharides, pigments and long-chain polyunsaturated fatty acid; it is especially effective in accumulating arachidonic acid (ARA). 28670342 9 79 theme ARA 1740:1742 arg1 yield 1744:1748 both biomass and ARA yield 1723:1748 both biomass and ARA yield in P. purpureum 1723:1764 CONCLUSIONS This work demonstrated a simple and effective strategy to promote both biomass and ARA yield in P. purpureum by introducing a small amount of 5-ALA. 27903321 6 0 theme metabolizable 920:932 arg1 energy 934:939 metabolizable energy 920:939 metabolizable energy 920:939 Equal amounts of metabolizable energy were fed to 36 second parity sows from day 105 of gestation and throughout lactation to study the impact on feed intake, plasma metabolites, milk production and litter performance. 27903321 14 1 theme energy 2345:2350 arg1 intake 2352:2357 energy intake 2345:2357 energy intake 2345:2357 Furthermore, the SBP diet seemed to impair feed intake and litter gain at peak lactation, suggesting that effects of the dietary fiber fraction on energy intake determines the potential inclusion level of fiber-rich ingredients. 27903321 14 2 theme litter 2257:2262 arg1 gain 2264:2267 litter gain 2257:2267 litter gain 2257:2267 Furthermore, the SBP diet seemed to impair feed intake and litter gain at peak lactation, suggesting that effects of the dietary fiber fraction on energy intake determines the potential inclusion level of fiber-rich ingredients. 27903321 12 3 theme litter 1970:1975 arg1 gain 1977:1980 litter gain 1970:1980 litter gain during the 3rd week of lactation 1970:2013 Feed intake tended to be lower (P=0.09), and litter gain during the 3rd week of lactation was decreased (P<0.05) in SBP sows. 27903321 14 4 theme fraction 2333:2340 arg1 effects 2304:2310 effects 2304:2310 effects of the dietary fiber fraction on energy intake 2304:2357 Furthermore, the SBP diet seemed to impair feed intake and litter gain at peak lactation, suggesting that effects of the dietary fiber fraction on energy intake determines the potential inclusion level of fiber-rich ingredients. 27903321 11 5 dep unaffected 1817:1826 arg1 whereas 1857:1863 whereas 1857:1863 whereas 1857:1863 Milk yield was unaffected by fiber treatment (P=0.43), whereas milk protein concentration was lowest in ALF sows (P<0.05). 27903321 3 6 theme dietary 510:516 arg1 fiber 518:522 dietary fiber 510:522 dietary fiber 510:522 Thus, a standard lactation diet low in dietary fiber, and two high-fiber diets based on sugar beet pulp (SBP) or alfalfa meal (ALF) were formulated. 27903321 7 7 dep days 1270:1273 arg1 24 1289:1290 24 1289:1290 24 1289:1290 Backfat thickness and BW of sows were recorded on days 3, 17 and 28 of lactation; blood was sampled on days 3 and 17; milk samples were obtained on days 3, 10, 17 and 24 of lactation; and piglets were weighed on days 2, 7, 14, 21 and 28 of lactation. 27903321 7 7 dep days 1270:1273 arg1 3 1275:1275 3 1275:1275 3 1275:1275 Backfat thickness and BW of sows were recorded on days 3, 17 and 28 of lactation; blood was sampled on days 3 and 17; milk samples were obtained on days 3, 10, 17 and 24 of lactation; and piglets were weighed on days 2, 7, 14, 21 and 28 of lactation. 27903321 6 8 theme plasma 1062:1067 arg1 metabolites 1069:1079 plasma metabolites 1062:1079 plasma metabolites 1062:1079 Equal amounts of metabolizable energy were fed to 36 second parity sows from day 105 of gestation and throughout lactation to study the impact on feed intake, plasma metabolites, milk production and litter performance. 27903321 3 9 theme low 503:505 arg1 diet 498:501 a standard lactation diet 477:501 a standard lactation diet low in dietary fiber 477:522 Thus, a standard lactation diet low in dietary fiber, and two high-fiber diets based on sugar beet pulp (SBP) or alfalfa meal (ALF) were formulated. 27903321 3 9 theme low 503:505 arg1 SBP 576:578 SBP 576:578 SBP 576:578 Thus, a standard lactation diet low in dietary fiber, and two high-fiber diets based on sugar beet pulp (SBP) or alfalfa meal (ALF) were formulated. 27903321 8 10 theme milk 1389:1392 arg1 yield 1394:1398 milk yield 1389:1398 milk yield 1389:1398 Litter gain and milk yield during late lactation were greater in sows fed C8TG or SOYO than in sows fed PFAD (P=0.05), whereas loss of BW (P=0.60) and backfat (P=0.70) was unaffected by fat source. 27903321 10 11 from day 1722:1724 arg1 day 1759:1761 day 17 1759:1764 day 17 1759:1764 The lowest concentration of plasma lactate on day 3 (P<0.05) and plasma acetate on day 17 (P<0.05) was observed in C8TG sows. 27903321 11 12 theme Milk 1802:1805 arg1 yield 1807:1811 Milk yield 1802:1811 Milk yield 1802:1811 Milk yield was unaffected by fiber treatment (P=0.43), whereas milk protein concentration was lowest in ALF sows (P<0.05). 27903321 2 13 theme Fiber 254:258 arg1 ingredients 260:270 Fiber ingredients 254:270 Fiber ingredients 254:270 Fiber ingredients may reduce feed intake and are often completely excluded from lactation diets, although locally available ingredients may be cost-efficient alternatives to partly replace cereals in lactation diets. 27903321 6 14 theme feed 1049:1052 arg1 intake 1054:1059 feed intake 1049:1059 feed intake 1049:1059 Equal amounts of metabolizable energy were fed to 36 second parity sows from day 105 of gestation and throughout lactation to study the impact on feed intake, plasma metabolites, milk production and litter performance. 27903321 6 15 from impact 1039:1044 arg1 intake 1054:1059 feed intake 1049:1059 feed intake 1049:1059 Equal amounts of metabolizable energy were fed to 36 second parity sows from day 105 of gestation and throughout lactation to study the impact on feed intake, plasma metabolites, milk production and litter performance. 27903321 6 15 from impact 1039:1044 arg1 metabolites 1069:1079 plasma metabolites 1062:1079 plasma metabolites 1062:1079 Equal amounts of metabolizable energy were fed to 36 second parity sows from day 105 of gestation and throughout lactation to study the impact on feed intake, plasma metabolites, milk production and litter performance. 27903321 6 15 from impact 1039:1044 arg1 production 1087:1096 milk production 1082:1096 milk production 1082:1096 Equal amounts of metabolizable energy were fed to 36 second parity sows from day 105 of gestation and throughout lactation to study the impact on feed intake, plasma metabolites, milk production and litter performance. 27903321 6 15 from impact 1039:1044 arg1 performance 1109:1119 litter performance 1102:1119 litter performance 1102:1119 Equal amounts of metabolizable energy were fed to 36 second parity sows from day 105 of gestation and throughout lactation to study the impact on feed intake, plasma metabolites, milk production and litter performance. 27903321 14 16 from effects 2304:2310 arg1 intake 2352:2357 energy intake 2345:2357 energy intake 2345:2357 Furthermore, the SBP diet seemed to impair feed intake and litter gain at peak lactation, suggesting that effects of the dietary fiber fraction on energy intake determines the potential inclusion level of fiber-rich ingredients. 27903321 1 17 theme fat 169:171 arg1 sources 173:179 fat sources 169:179 fat sources 169:179 Sow lactation diets often include fat sources without considering the impact on digestion, metabolism and performance. 27903321 14 18 theme peak 2272:2275 arg1 lactation 2277:2285 peak lactation 2272:2285 peak lactation 2272:2285 Furthermore, the SBP diet seemed to impair feed intake and litter gain at peak lactation, suggesting that effects of the dietary fiber fraction on energy intake determines the potential inclusion level of fiber-rich ingredients. 27903321 9 19 theme Milk 1571:1574 arg1 protein 1576:1582 Milk protein 1571:1582 Milk protein on days 3 and 10 of lactation 1571:1612 Milk protein on days 3 and 10 of lactation were lower in C8TG and SOYO sows, than in PFAD sows (P<0.05). 27903321 2 20 dep reduce 276:281 arg1 although 351:358 although 351:358 although 351:358 Fiber ingredients may reduce feed intake and are often completely excluded from lactation diets, although locally available ingredients may be cost-efficient alternatives to partly replace cereals in lactation diets. 27903321 6 21 theme litter 1102:1107 arg1 performance 1109:1119 litter performance 1102:1119 litter performance 1102:1119 Equal amounts of metabolizable energy were fed to 36 second parity sows from day 105 of gestation and throughout lactation to study the impact on feed intake, plasma metabolites, milk production and litter performance. 27903321 5 22 theme dietary 883:889 arg1 diet 733:736 Each diet 728:736 Each diet 728:736 Each diet was divided in three portions and combined with 3% soybean oil (SOYO), palm fatty acid distillate (PFAD), or glycerol trioctanoate (C8TG) as the dietary fat source. 27903321 5 22 theme dietary 883:889 arg1 source 895:900 the dietary fat source 879:900 the dietary fat source 879:900 Each diet was divided in three portions and combined with 3% soybean oil (SOYO), palm fatty acid distillate (PFAD), or glycerol trioctanoate (C8TG) as the dietary fat source. 27903321 4 23 from high 705:708 arg1 NSP 723:725 insoluble NSP 713:725 insoluble NSP 713:725 The SBP diet was high in soluble non-starch polysaccharides (NSP), whereas ALF being high in insoluble NSP. 27903321 0 24 from metabolites 63:73 arg1 sows 129:132 sows 129:132 sows 129:132 Impact of fat source and dietary fibers on feed intake, plasma metabolites, litter gain and the yield and composition of milk in sows. 27903321 7 25 theme sows 1150:1153 arg1 BW 1144:1145 BW 1144:1145 BW 1144:1145 Backfat thickness and BW of sows were recorded on days 3, 17 and 28 of lactation; blood was sampled on days 3 and 17; milk samples were obtained on days 3, 10, 17 and 24 of lactation; and piglets were weighed on days 2, 7, 14, 21 and 28 of lactation. 27903321 7 25 theme sows 1150:1153 arg1 thickness 1130:1138 Backfat thickness 1122:1138 Backfat thickness 1122:1138 Backfat thickness and BW of sows were recorded on days 3, 17 and 28 of lactation; blood was sampled on days 3 and 17; milk samples were obtained on days 3, 10, 17 and 24 of lactation; and piglets were weighed on days 2, 7, 14, 21 and 28 of lactation. 27903321 12 26 theme SBP 2041:2043 arg1 sows 2045:2048 SBP sows 2041:2048 SBP sows 2041:2048 Feed intake tended to be lower (P=0.09), and litter gain during the 3rd week of lactation was decreased (P<0.05) in SBP sows. 27903321 8 27 theme fat 1559:1561 arg1 source 1563:1568 fat source 1559:1568 fat source 1559:1568 Litter gain and milk yield during late lactation were greater in sows fed C8TG or SOYO than in sows fed PFAD (P=0.05), whereas loss of BW (P=0.60) and backfat (P=0.70) was unaffected by fat source. 27903321 3 28 theme beet 565:568 arg1 pulp 570:573 sugar beet pulp 559:573 sugar beet pulp 559:573 Thus, a standard lactation diet low in dietary fiber, and two high-fiber diets based on sugar beet pulp (SBP) or alfalfa meal (ALF) were formulated. 27903321 0 29 dep yield 96:100 arg1 the 92:94 the 92:94 the 92:94 Impact of fat source and dietary fibers on feed intake, plasma metabolites, litter gain and the yield and composition of milk in sows. 27903321 0 30 theme milk 121:124 arg1 yield 96:100 yield 96:100 yield 96:100 Impact of fat source and dietary fibers on feed intake, plasma metabolites, litter gain and the yield and composition of milk in sows. 27903321 0 30 theme milk 121:124 arg1 composition 106:116 composition 106:116 composition 106:116 Impact of fat source and dietary fibers on feed intake, plasma metabolites, litter gain and the yield and composition of milk in sows. 27903321 0 30 theme milk 121:124 arg1 intake 48:53 feed intake 43:53 feed intake 43:53 Impact of fat source and dietary fibers on feed intake, plasma metabolites, litter gain and the yield and composition of milk in sows. 27903321 0 30 theme milk 121:124 arg1 metabolites 63:73 plasma metabolites 56:73 plasma metabolites 56:73 Impact of fat source and dietary fibers on feed intake, plasma metabolites, litter gain and the yield and composition of milk in sows. 27903321 0 30 theme milk 121:124 arg1 gain 83:86 litter gain 76:86 litter gain 76:86 Impact of fat source and dietary fibers on feed intake, plasma metabolites, litter gain and the yield and composition of milk in sows. 27903321 3 31 from low 503:505 arg1 fiber 518:522 dietary fiber 510:522 dietary fiber 510:522 Thus, a standard lactation diet low in dietary fiber, and two high-fiber diets based on sugar beet pulp (SBP) or alfalfa meal (ALF) were formulated. 27903321 2 32 dep partly 428:433 arg1 replace 435:441 replace 435:441 replace cereals in lactation diets 435:468 Fiber ingredients may reduce feed intake and are often completely excluded from lactation diets, although locally available ingredients may be cost-efficient alternatives to partly replace cereals in lactation diets. 27903321 5 33 theme % 787:787 arg1 oil 797:799 3% soybean oil 786:799 3% soybean oil (SOYO) 786:806 Each diet was divided in three portions and combined with 3% soybean oil (SOYO), palm fatty acid distillate (PFAD), or glycerol trioctanoate (C8TG) as the dietary fat source. 27903321 5 33 theme % 787:787 arg1 SOYO 802:805 SOYO 802:805 SOYO 802:805 Each diet was divided in three portions and combined with 3% soybean oil (SOYO), palm fatty acid distillate (PFAD), or glycerol trioctanoate (C8TG) as the dietary fat source. 27903321 0 34 from Impact 0:5 arg1 yield 96:100 yield 96:100 yield 96:100 Impact of fat source and dietary fibers on feed intake, plasma metabolites, litter gain and the yield and composition of milk in sows. 27903321 0 34 from Impact 0:5 arg1 intake 48:53 feed intake 43:53 feed intake 43:53 Impact of fat source and dietary fibers on feed intake, plasma metabolites, litter gain and the yield and composition of milk in sows. 27903321 0 34 from Impact 0:5 arg1 metabolites 63:73 plasma metabolites 56:73 plasma metabolites 56:73 Impact of fat source and dietary fibers on feed intake, plasma metabolites, litter gain and the yield and composition of milk in sows. 27903321 0 34 from Impact 0:5 arg1 gain 83:86 litter gain 76:86 litter gain 76:86 Impact of fat source and dietary fibers on feed intake, plasma metabolites, litter gain and the yield and composition of milk in sows. 27903321 11 35 theme milk 1865:1868 arg1 concentration 1878:1890 milk protein concentration 1865:1890 milk protein concentration 1865:1890 Milk yield was unaffected by fiber treatment (P=0.43), whereas milk protein concentration was lowest in ALF sows (P<0.05). 27903321 14 36 theme dietary 2319:2325 arg1 fraction 2333:2340 the dietary fiber fraction 2315:2340 the dietary fiber fraction 2315:2340 Furthermore, the SBP diet seemed to impair feed intake and litter gain at peak lactation, suggesting that effects of the dietary fiber fraction on energy intake determines the potential inclusion level of fiber-rich ingredients. 27903321 11 37 dep lowest 1896:1901 arg1 P<0.05 1916:1921 P<0.05 1916:1921 P<0.05 1916:1921 Milk yield was unaffected by fiber treatment (P=0.43), whereas milk protein concentration was lowest in ALF sows (P<0.05). 27903321 7 38 theme lactation 1362:1370 arg1 days 1334:1337 days 2, 7, 14, 21 and 28 1334:1357 days 1334:1337 Backfat thickness and BW of sows were recorded on days 3, 17 and 28 of lactation; blood was sampled on days 3 and 17; milk samples were obtained on days 3, 10, 17 and 24 of lactation; and piglets were weighed on days 2, 7, 14, 21 and 28 of lactation. 27903321 9 39 theme lactation 1604:1612 arg1 days 1587:1590 days 3 and 10 1587:1599 days 1587:1590 Milk protein on days 3 and 10 of lactation were lower in C8TG and SOYO sows, than in PFAD sows (P<0.05). 27903321 0 40 theme litter 76:81 arg1 gain 83:86 litter gain 76:86 litter gain 76:86 Impact of fat source and dietary fibers on feed intake, plasma metabolites, litter gain and the yield and composition of milk in sows. 27903321 14 41 theme inclusion 2384:2392 arg1 level 2394:2398 the potential inclusion level 2370:2398 the potential inclusion level of fiber-rich ingredients 2370:2424 Furthermore, the SBP diet seemed to impair feed intake and litter gain at peak lactation, suggesting that effects of the dietary fiber fraction on energy intake determines the potential inclusion level of fiber-rich ingredients. 27903321 4 42 from polysaccharides 664:678 arg1 diet 628:631 The SBP diet 620:631 The SBP diet 620:631 The SBP diet was high in soluble non-starch polysaccharides (NSP), whereas ALF being high in insoluble NSP. 27903321 4 42 from polysaccharides 664:678 arg1 whereas 687:693 whereas 687:693 whereas 687:693 The SBP diet was high in soluble non-starch polysaccharides (NSP), whereas ALF being high in insoluble NSP. 27903321 4 42 from polysaccharides 664:678 arg1 high 637:640 high 637:640 high 637:640 The SBP diet was high in soluble non-starch polysaccharides (NSP), whereas ALF being high in insoluble NSP. 27903321 6 43 theme Equal 903:907 arg1 energy 934:939 metabolizable energy 920:939 metabolizable energy 920:939 Equal amounts of metabolizable energy were fed to 36 second parity sows from day 105 of gestation and throughout lactation to study the impact on feed intake, plasma metabolites, milk production and litter performance. 27903321 6 43 theme Equal 903:907 arg1 amounts 909:915 Equal amounts 903:915 Equal amounts of metabolizable energy 903:939 Equal amounts of metabolizable energy were fed to 36 second parity sows from day 105 of gestation and throughout lactation to study the impact on feed intake, plasma metabolites, milk production and litter performance. 27903321 2 44 from cereals 443:449 arg1 diets 464:468 lactation diets 454:468 lactation diets 454:468 Fiber ingredients may reduce feed intake and are often completely excluded from lactation diets, although locally available ingredients may be cost-efficient alternatives to partly replace cereals in lactation diets. 27903321 4 45 theme soluble 645:651 arg1 NSP 681:683 NSP 681:683 NSP 681:683 The SBP diet was high in soluble non-starch polysaccharides (NSP), whereas ALF being high in insoluble NSP. 27903321 4 45 theme soluble 645:651 arg1 polysaccharides 664:678 soluble non-starch polysaccharides 645:678 soluble non-starch polysaccharides (NSP) 645:684 The SBP diet was high in soluble non-starch polysaccharides (NSP), whereas ALF being high in insoluble NSP. 27903321 14 46 theme fiber-rich 2403:2412 arg1 ingredients 2414:2424 fiber-rich ingredients 2403:2424 fiber-rich ingredients 2403:2424 Furthermore, the SBP diet seemed to impair feed intake and litter gain at peak lactation, suggesting that effects of the dietary fiber fraction on energy intake determines the potential inclusion level of fiber-rich ingredients. 27903321 9 47 theme SOYO 1637:1640 arg1 sows 1642:1645 SOYO sows 1637:1645 SOYO sows 1637:1645 Milk protein on days 3 and 10 of lactation were lower in C8TG and SOYO sows, than in PFAD sows (P<0.05). 27903321 2 48 theme cost-efficient 397:410 arg1 alternatives 412:423 cost-efficient alternatives 397:423 cost-efficient alternatives to partly replace cereals in lactation diets 397:468 Fiber ingredients may reduce feed intake and are often completely excluded from lactation diets, although locally available ingredients may be cost-efficient alternatives to partly replace cereals in lactation diets. 27903321 0 49 theme fat 10:12 arg1 source 14:19 fat source 10:19 fat source 10:19 Impact of fat source and dietary fibers on feed intake, plasma metabolites, litter gain and the yield and composition of milk in sows. 27903321 5 50 theme fatty 814:818 arg1 distillate 825:834 palm fatty acid distillate 809:834 palm fatty acid distillate (PFAD) 809:841 Each diet was divided in three portions and combined with 3% soybean oil (SOYO), palm fatty acid distillate (PFAD), or glycerol trioctanoate (C8TG) as the dietary fat source. 27903321 5 50 theme fatty 814:818 arg1 PFAD 837:840 PFAD 837:840 PFAD 837:840 Each diet was divided in three portions and combined with 3% soybean oil (SOYO), palm fatty acid distillate (PFAD), or glycerol trioctanoate (C8TG) as the dietary fat source. 27903321 7 51 theme Backfat 1122:1128 arg1 thickness 1130:1138 Backfat thickness 1122:1138 Backfat thickness 1122:1138 Backfat thickness and BW of sows were recorded on days 3, 17 and 28 of lactation; blood was sampled on days 3 and 17; milk samples were obtained on days 3, 10, 17 and 24 of lactation; and piglets were weighed on days 2, 7, 14, 21 and 28 of lactation. 27903321 3 52 theme alfalfa 584:590 arg1 ALF 598:600 ALF 598:600 ALF 598:600 Thus, a standard lactation diet low in dietary fiber, and two high-fiber diets based on sugar beet pulp (SBP) or alfalfa meal (ALF) were formulated. 27903321 3 52 theme alfalfa 584:590 arg1 meal 592:595 alfalfa meal 584:595 alfalfa meal (ALF) 584:601 Thus, a standard lactation diet low in dietary fiber, and two high-fiber diets based on sugar beet pulp (SBP) or alfalfa meal (ALF) were formulated. 27903321 4 53 theme insoluble 713:721 arg1 NSP 723:725 insoluble NSP 713:725 insoluble NSP 713:725 The SBP diet was high in soluble non-starch polysaccharides (NSP), whereas ALF being high in insoluble NSP. 27903321 2 54 theme available 368:376 arg1 ingredients 378:388 locally available ingredients 360:388 locally available ingredients 360:388 Fiber ingredients may reduce feed intake and are often completely excluded from lactation diets, although locally available ingredients may be cost-efficient alternatives to partly replace cereals in lactation diets. 27903321 14 55 theme potential 2374:2382 arg1 level 2394:2398 the potential inclusion level 2370:2398 the potential inclusion level of fiber-rich ingredients 2370:2424 Furthermore, the SBP diet seemed to impair feed intake and litter gain at peak lactation, suggesting that effects of the dietary fiber fraction on energy intake determines the potential inclusion level of fiber-rich ingredients. 27903321 0 56 theme feed 43:46 arg1 intake 48:53 feed intake 43:53 feed intake 43:53 Impact of fat source and dietary fibers on feed intake, plasma metabolites, litter gain and the yield and composition of milk in sows. 27903321 0 57 theme fibers 33:38 arg1 Impact 0:5 Impact 0:5 Impact of fat source and dietary fibers on feed intake, plasma metabolites, litter gain and the yield and composition of milk in sows. 0:133 Impact of fat source and dietary fibers on feed intake, plasma metabolites, litter gain and the yield and composition of milk in sows. 27903321 8 58 theme BW 1508:1509 arg1 loss 1500:1503 loss 1500:1503 loss of BW (P=0.60) and backfat (P=0.70) 1500:1539 Litter gain and milk yield during late lactation were greater in sows fed C8TG or SOYO than in sows fed PFAD (P=0.05), whereas loss of BW (P=0.60) and backfat (P=0.70) was unaffected by fat source. 27903321 13 59 theme reduced 2158:2164 arg1 intake 2173:2178 reduced energy intake 2158:2178 reduced energy intake in PFAD-fed sows 2158:2195 In conclusion, performance was enhanced in SOYO and C8TG compared with PFAD sows, possibly associated with reduced energy intake in PFAD-fed sows. 27903321 0 60 from yield 96:100 arg1 sows 129:132 sows 129:132 sows 129:132 Impact of fat source and dietary fibers on feed intake, plasma metabolites, litter gain and the yield and composition of milk in sows. 27903321 1 61 dep diets 149:153 arg1 include 161:167 include 161:167 diets often include fat sources without considering the impact on digestion, metabolism and performance 149:251 Sow lactation diets often include fat sources without considering the impact on digestion, metabolism and performance. 27903321 3 62 theme standard 479:486 arg1 diet 498:501 a standard lactation diet 477:501 a standard lactation diet low in dietary fiber 477:522 Thus, a standard lactation diet low in dietary fiber, and two high-fiber diets based on sugar beet pulp (SBP) or alfalfa meal (ALF) were formulated. 27903321 3 62 theme standard 479:486 arg1 SBP 576:578 SBP 576:578 SBP 576:578 Thus, a standard lactation diet low in dietary fiber, and two high-fiber diets based on sugar beet pulp (SBP) or alfalfa meal (ALF) were formulated. 27903321 7 63 theme milk 1240:1243 arg1 samples 1245:1251 milk samples 1240:1251 milk samples 1240:1251 Backfat thickness and BW of sows were recorded on days 3, 17 and 28 of lactation; blood was sampled on days 3 and 17; milk samples were obtained on days 3, 10, 17 and 24 of lactation; and piglets were weighed on days 2, 7, 14, 21 and 28 of lactation. 27903321 5 64 theme glycerol 847:854 arg1 C8TG 870:873 C8TG 870:873 C8TG 870:873 Each diet was divided in three portions and combined with 3% soybean oil (SOYO), palm fatty acid distillate (PFAD), or glycerol trioctanoate (C8TG) as the dietary fat source. 27903321 5 64 theme glycerol 847:854 arg1 trioctanoate 856:867 glycerol trioctanoate 847:867 glycerol trioctanoate (C8TG) 847:874 Each diet was divided in three portions and combined with 3% soybean oil (SOYO), palm fatty acid distillate (PFAD), or glycerol trioctanoate (C8TG) as the dietary fat source. 27903321 6 65 theme energy 934:939 arg1 energy 934:939 metabolizable energy 920:939 metabolizable energy 920:939 Equal amounts of metabolizable energy were fed to 36 second parity sows from day 105 of gestation and throughout lactation to study the impact on feed intake, plasma metabolites, milk production and litter performance. 27903321 6 65 theme energy 934:939 arg1 amounts 909:915 Equal amounts 903:915 Equal amounts of metabolizable energy 903:939 Equal amounts of metabolizable energy were fed to 36 second parity sows from day 105 of gestation and throughout lactation to study the impact on feed intake, plasma metabolites, milk production and litter performance. 27903321 11 66 theme fiber 1831:1835 arg1 treatment 1837:1845 fiber treatment 1831:1845 fiber treatment (P=0.43) 1831:1854 Milk yield was unaffected by fiber treatment (P=0.43), whereas milk protein concentration was lowest in ALF sows (P<0.05). 27903321 11 66 theme fiber 1831:1835 arg1 P=0.43 1848:1853 P=0.43 1848:1853 P=0.43 1848:1853 Milk yield was unaffected by fiber treatment (P=0.43), whereas milk protein concentration was lowest in ALF sows (P<0.05). 27903321 6 67 theme milk 1082:1085 arg1 production 1087:1096 milk production 1082:1096 milk production 1082:1096 Equal amounts of metabolizable energy were fed to 36 second parity sows from day 105 of gestation and throughout lactation to study the impact on feed intake, plasma metabolites, milk production and litter performance. 27903321 9 68 dep lower 1619:1623 arg1 P<0.05 1667:1672 P<0.05 1667:1672 P<0.05 1667:1672 Milk protein on days 3 and 10 of lactation were lower in C8TG and SOYO sows, than in PFAD sows (P<0.05). 27903321 6 69 theme gestation 991:999 arg1 day 980:982 day 105 980:986 day 105 of gestation 980:999 Equal amounts of metabolizable energy were fed to 36 second parity sows from day 105 of gestation and throughout lactation to study the impact on feed intake, plasma metabolites, milk production and litter performance. 27903321 0 70 from composition 106:116 arg1 sows 129:132 sows 129:132 sows 129:132 Impact of fat source and dietary fibers on feed intake, plasma metabolites, litter gain and the yield and composition of milk in sows. 27903321 14 71 theme fiber 2327:2331 arg1 fraction 2333:2340 the dietary fiber fraction 2315:2340 the dietary fiber fraction 2315:2340 Furthermore, the SBP diet seemed to impair feed intake and litter gain at peak lactation, suggesting that effects of the dietary fiber fraction on energy intake determines the potential inclusion level of fiber-rich ingredients. 27903321 8 72 theme Litter 1373:1378 arg1 gain 1380:1383 Litter gain 1373:1383 Litter gain 1373:1383 Litter gain and milk yield during late lactation were greater in sows fed C8TG or SOYO than in sows fed PFAD (P=0.05), whereas loss of BW (P=0.60) and backfat (P=0.70) was unaffected by fat source. 27903321 7 73 dep days 1172:1175 arg1 3 1177:1177 3 1177:1177 3 1177:1177 Backfat thickness and BW of sows were recorded on days 3, 17 and 28 of lactation; blood was sampled on days 3 and 17; milk samples were obtained on days 3, 10, 17 and 24 of lactation; and piglets were weighed on days 2, 7, 14, 21 and 28 of lactation. 27903321 7 73 dep days 1172:1175 arg1 28 1187:1188 28 1187:1188 28 1187:1188 Backfat thickness and BW of sows were recorded on days 3, 17 and 28 of lactation; blood was sampled on days 3 and 17; milk samples were obtained on days 3, 10, 17 and 24 of lactation; and piglets were weighed on days 2, 7, 14, 21 and 28 of lactation. 27903321 14 74 theme feed 2241:2244 arg1 intake 2246:2251 feed intake 2241:2251 feed intake 2241:2251 Furthermore, the SBP diet seemed to impair feed intake and litter gain at peak lactation, suggesting that effects of the dietary fiber fraction on energy intake determines the potential inclusion level of fiber-rich ingredients. 27903321 13 75 theme PFAD 2122:2125 arg1 sows 2127:2130 PFAD sows 2122:2130 PFAD sows 2122:2130 In conclusion, performance was enhanced in SOYO and C8TG compared with PFAD sows, possibly associated with reduced energy intake in PFAD-fed sows. 27903321 1 76 theme Sow 135:137 arg1 lactation 139:147 Sow lactation 135:147 Sow lactation 135:147 Sow lactation diets often include fat sources without considering the impact on digestion, metabolism and performance. 27903321 10 77 theme C8TG 1791:1794 arg1 sows 1796:1799 C8TG sows 1791:1799 C8TG sows 1791:1799 The lowest concentration of plasma lactate on day 3 (P<0.05) and plasma acetate on day 17 (P<0.05) was observed in C8TG sows. 27903321 7 78 theme lactation 1193:1201 arg1 days 1172:1175 days 3, 17 and 28 1172:1188 days 3, 17 and 28 of lactation 1172:1201 Backfat thickness and BW of sows were recorded on days 3, 17 and 28 of lactation; blood was sampled on days 3 and 17; milk samples were obtained on days 3, 10, 17 and 24 of lactation; and piglets were weighed on days 2, 7, 14, 21 and 28 of lactation. 27903321 8 79 theme backfat 1524:1530 arg1 loss 1500:1503 loss 1500:1503 loss of BW (P=0.60) and backfat (P=0.70) 1500:1539 Litter gain and milk yield during late lactation were greater in sows fed C8TG or SOYO than in sows fed PFAD (P=0.05), whereas loss of BW (P=0.60) and backfat (P=0.70) was unaffected by fat source. 27903321 13 80 from intake 2173:2178 arg1 sows 2192:2195 PFAD-fed sows 2183:2195 PFAD-fed sows 2183:2195 In conclusion, performance was enhanced in SOYO and C8TG compared with PFAD sows, possibly associated with reduced energy intake in PFAD-fed sows. 27903321 6 81 theme parity 963:968 arg1 sows 970:973 36 second parity sows 953:973 36 second parity sows from day 105 of gestation and throughout lactation 953:1024 Equal amounts of metabolizable energy were fed to 36 second parity sows from day 105 of gestation and throughout lactation to study the impact on feed intake, plasma metabolites, milk production and litter performance. 27903321 10 82 theme lowest 1680:1685 arg1 concentration 1687:1699 The lowest concentration 1676:1699 The lowest concentration of plasma lactate on day 3 (P<0.05) and plasma acetate on day 17 (P<0.05) 1676:1773 The lowest concentration of plasma lactate on day 3 (P<0.05) and plasma acetate on day 17 (P<0.05) was observed in C8TG sows. 27903321 1 83 from impact 205:210 arg1 performance 241:251 performance 241:251 performance 241:251 Sow lactation diets often include fat sources without considering the impact on digestion, metabolism and performance. 27903321 1 83 from impact 205:210 arg1 metabolism 226:235 metabolism 226:235 metabolism 226:235 Sow lactation diets often include fat sources without considering the impact on digestion, metabolism and performance. 27903321 1 83 from impact 205:210 arg1 digestion 215:223 digestion 215:223 digestion 215:223 Sow lactation diets often include fat sources without considering the impact on digestion, metabolism and performance. 27903321 8 84 theme late 1407:1410 arg1 lactation 1412:1420 late lactation 1407:1420 late lactation 1407:1420 Litter gain and milk yield during late lactation were greater in sows fed C8TG or SOYO than in sows fed PFAD (P=0.05), whereas loss of BW (P=0.60) and backfat (P=0.70) was unaffected by fat source. 27903321 12 85 dep decreased 2019:2027 arg1 P<0.05 2030:2035 P<0.05 2030:2035 P<0.05 2030:2035 Feed intake tended to be lower (P=0.09), and litter gain during the 3rd week of lactation was decreased (P<0.05) in SBP sows. 27903321 0 86 from intake 48:53 arg1 sows 129:132 sows 129:132 sows 129:132 Impact of fat source and dietary fibers on feed intake, plasma metabolites, litter gain and the yield and composition of milk in sows. 27903321 3 87 theme high-fiber 533:542 arg1 diets 544:548 two high-fiber diets 529:548 two high-fiber diets 529:548 Thus, a standard lactation diet low in dietary fiber, and two high-fiber diets based on sugar beet pulp (SBP) or alfalfa meal (ALF) were formulated. 27903321 4 88 from NSP 723:725 arg1 high 705:708 high 705:708 high 705:708 The SBP diet was high in soluble non-starch polysaccharides (NSP), whereas ALF being high in insoluble NSP. 27903321 5 89 theme soybean 789:795 arg1 oil 797:799 3% soybean oil 786:799 3% soybean oil (SOYO) 786:806 Each diet was divided in three portions and combined with 3% soybean oil (SOYO), palm fatty acid distillate (PFAD), or glycerol trioctanoate (C8TG) as the dietary fat source. 27903321 5 89 theme soybean 789:795 arg1 SOYO 802:805 SOYO 802:805 SOYO 802:805 Each diet was divided in three portions and combined with 3% soybean oil (SOYO), palm fatty acid distillate (PFAD), or glycerol trioctanoate (C8TG) as the dietary fat source. 27903321 11 90 theme ALF 1906:1908 arg1 sows 1910:1913 ALF sows 1906:1913 ALF sows 1906:1913 Milk yield was unaffected by fiber treatment (P=0.43), whereas milk protein concentration was lowest in ALF sows (P<0.05). 27903321 0 91 from gain 83:86 arg1 sows 129:132 sows 129:132 sows 129:132 Impact of fat source and dietary fibers on feed intake, plasma metabolites, litter gain and the yield and composition of milk in sows. 27903321 10 92 theme lactate 1711:1717 arg1 concentration 1687:1699 The lowest concentration 1676:1699 The lowest concentration of plasma lactate on day 3 (P<0.05) and plasma acetate on day 17 (P<0.05) 1676:1773 The lowest concentration of plasma lactate on day 3 (P<0.05) and plasma acetate on day 17 (P<0.05) was observed in C8TG sows. 27903321 4 93 theme SBP 624:626 arg1 diet 628:631 The SBP diet 620:631 The SBP diet 620:631 The SBP diet was high in soluble non-starch polysaccharides (NSP), whereas ALF being high in insoluble NSP. 27903321 4 93 theme SBP 624:626 arg1 whereas 687:693 whereas 687:693 whereas 687:693 The SBP diet was high in soluble non-starch polysaccharides (NSP), whereas ALF being high in insoluble NSP. 27903321 4 93 theme SBP 624:626 arg1 high 637:640 high 637:640 high 637:640 The SBP diet was high in soluble non-starch polysaccharides (NSP), whereas ALF being high in insoluble NSP. 27903321 3 94 from fiber 518:522 arg1 low 503:505 low 503:505 low 503:505 Thus, a standard lactation diet low in dietary fiber, and two high-fiber diets based on sugar beet pulp (SBP) or alfalfa meal (ALF) were formulated. 27903321 10 95 theme plasma 1704:1709 arg1 lactate 1711:1717 plasma lactate 1704:1717 plasma lactate 1704:1717 The lowest concentration of plasma lactate on day 3 (P<0.05) and plasma acetate on day 17 (P<0.05) was observed in C8TG sows. 27903321 10 96 from acetate 1748:1754 arg1 day 1759:1761 day 17 1759:1764 day 17 1759:1764 The lowest concentration of plasma lactate on day 3 (P<0.05) and plasma acetate on day 17 (P<0.05) was observed in C8TG sows. 27903321 5 97 theme fat 891:893 arg1 diet 733:736 Each diet 728:736 Each diet 728:736 Each diet was divided in three portions and combined with 3% soybean oil (SOYO), palm fatty acid distillate (PFAD), or glycerol trioctanoate (C8TG) as the dietary fat source. 27903321 5 97 theme fat 891:893 arg1 source 895:900 the dietary fat source 879:900 the dietary fat source 879:900 Each diet was divided in three portions and combined with 3% soybean oil (SOYO), palm fatty acid distillate (PFAD), or glycerol trioctanoate (C8TG) as the dietary fat source. 27903321 3 98 theme sugar 559:563 arg1 pulp 570:573 sugar beet pulp 559:573 sugar beet pulp 559:573 Thus, a standard lactation diet low in dietary fiber, and two high-fiber diets based on sugar beet pulp (SBP) or alfalfa meal (ALF) were formulated. 27903321 7 99 theme lactation 1295:1303 arg1 days 1270:1273 days 3, 10, 17 and 24 1270:1290 days 3, 10, 17 and 24 of lactation 1270:1303 Backfat thickness and BW of sows were recorded on days 3, 17 and 28 of lactation; blood was sampled on days 3 and 17; milk samples were obtained on days 3, 10, 17 and 24 of lactation; and piglets were weighed on days 2, 7, 14, 21 and 28 of lactation. 27903321 0 100 theme plasma 56:61 arg1 metabolites 63:73 plasma metabolites 56:73 plasma metabolites 56:73 Impact of fat source and dietary fibers on feed intake, plasma metabolites, litter gain and the yield and composition of milk in sows. 27903321 12 101 dep lower 1950:1954 arg1 P=0.09 1957:1962 P=0.09 1957:1962 P=0.09 1957:1962 Feed intake tended to be lower (P=0.09), and litter gain during the 3rd week of lactation was decreased (P<0.05) in SBP sows. 27903321 5 102 theme 3 786:786 arg1 % 787:787 % 787:787 % 787:787 Each diet was divided in three portions and combined with 3% soybean oil (SOYO), palm fatty acid distillate (PFAD), or glycerol trioctanoate (C8TG) as the dietary fat source. 27903321 2 103 theme lactation 454:462 arg1 diets 464:468 lactation diets 454:468 lactation diets 454:468 Fiber ingredients may reduce feed intake and are often completely excluded from lactation diets, although locally available ingredients may be cost-efficient alternatives to partly replace cereals in lactation diets. 27903321 5 104 theme acid 820:823 arg1 distillate 825:834 palm fatty acid distillate 809:834 palm fatty acid distillate (PFAD) 809:841 Each diet was divided in three portions and combined with 3% soybean oil (SOYO), palm fatty acid distillate (PFAD), or glycerol trioctanoate (C8TG) as the dietary fat source. 27903321 5 104 theme acid 820:823 arg1 PFAD 837:840 PFAD 837:840 PFAD 837:840 Each diet was divided in three portions and combined with 3% soybean oil (SOYO), palm fatty acid distillate (PFAD), or glycerol trioctanoate (C8TG) as the dietary fat source. 27903321 10 105 theme plasma 1741:1746 arg1 acetate 1748:1754 plasma acetate 1741:1754 plasma acetate on day 17 (P<0.05) 1741:1773 The lowest concentration of plasma lactate on day 3 (P<0.05) and plasma acetate on day 17 (P<0.05) was observed in C8TG sows. 27903321 10 105 theme plasma 1741:1746 arg1 P<0.05 1767:1772 P<0.05 1767:1772 P<0.05 1767:1772 The lowest concentration of plasma lactate on day 3 (P<0.05) and plasma acetate on day 17 (P<0.05) was observed in C8TG sows. 27903321 12 106 theme lactation 2005:2013 arg1 week 1997:2000 the 3rd week 1989:2000 the 3rd week of lactation 1989:2013 Feed intake tended to be lower (P=0.09), and litter gain during the 3rd week of lactation was decreased (P<0.05) in SBP sows. 27903321 14 107 theme ingredients 2414:2424 arg1 level 2394:2398 the potential inclusion level 2370:2398 the potential inclusion level of fiber-rich ingredients 2370:2424 Furthermore, the SBP diet seemed to impair feed intake and litter gain at peak lactation, suggesting that effects of the dietary fiber fraction on energy intake determines the potential inclusion level of fiber-rich ingredients. 27903321 13 108 theme PFAD-fed 2183:2190 arg1 sows 2192:2195 PFAD-fed sows 2183:2195 PFAD-fed sows 2183:2195 In conclusion, performance was enhanced in SOYO and C8TG compared with PFAD sows, possibly associated with reduced energy intake in PFAD-fed sows. 27903321 4 109 dep high 637:640 arg1 diet 628:631 The SBP diet 620:631 The SBP diet 620:631 The SBP diet was high in soluble non-starch polysaccharides (NSP), whereas ALF being high in insoluble NSP. 27903321 4 109 dep high 637:640 arg1 whereas 687:693 whereas 687:693 whereas 687:693 The SBP diet was high in soluble non-starch polysaccharides (NSP), whereas ALF being high in insoluble NSP. 27903321 4 109 dep high 637:640 arg1 high 637:640 high 637:640 high 637:640 The SBP diet was high in soluble non-starch polysaccharides (NSP), whereas ALF being high in insoluble NSP. 27903321 9 110 from protein 1576:1582 arg1 days 1587:1590 days 3 and 10 1587:1599 days 1587:1590 Milk protein on days 3 and 10 of lactation were lower in C8TG and SOYO sows, than in PFAD sows (P<0.05). 27903321 9 110 from protein 1576:1582 arg1 10 1598:1599 10 1598:1599 10 1598:1599 Milk protein on days 3 and 10 of lactation were lower in C8TG and SOYO sows, than in PFAD sows (P<0.05). 27903321 11 111 theme protein 1870:1876 arg1 concentration 1878:1890 milk protein concentration 1865:1890 milk protein concentration 1865:1890 Milk yield was unaffected by fiber treatment (P=0.43), whereas milk protein concentration was lowest in ALF sows (P<0.05). 27903321 2 112 theme lactation 334:342 arg1 diets 344:348 lactation diets 334:348 lactation diets 334:348 Fiber ingredients may reduce feed intake and are often completely excluded from lactation diets, although locally available ingredients may be cost-efficient alternatives to partly replace cereals in lactation diets. 27903321 0 113 theme source 14:19 arg1 Impact 0:5 Impact 0:5 Impact of fat source and dietary fibers on feed intake, plasma metabolites, litter gain and the yield and composition of milk in sows. 0:133 Impact of fat source and dietary fibers on feed intake, plasma metabolites, litter gain and the yield and composition of milk in sows. 27903321 5 114 theme palm 809:812 arg1 distillate 825:834 palm fatty acid distillate 809:834 palm fatty acid distillate (PFAD) 809:841 Each diet was divided in three portions and combined with 3% soybean oil (SOYO), palm fatty acid distillate (PFAD), or glycerol trioctanoate (C8TG) as the dietary fat source. 27903321 5 114 theme palm 809:812 arg1 PFAD 837:840 PFAD 837:840 PFAD 837:840 Each diet was divided in three portions and combined with 3% soybean oil (SOYO), palm fatty acid distillate (PFAD), or glycerol trioctanoate (C8TG) as the dietary fat source. 27903321 14 115 theme SBP 2215:2217 arg1 diet 2219:2222 the SBP diet 2211:2222 the SBP diet 2211:2222 Furthermore, the SBP diet seemed to impair feed intake and litter gain at peak lactation, suggesting that effects of the dietary fiber fraction on energy intake determines the potential inclusion level of fiber-rich ingredients. 27903321 10 116 located observed 1779:1786 arg1 sows 1796:1799 C8TG sows 1791:1799 C8TG sows 1791:1799 The lowest concentration of plasma lactate on day 3 (P<0.05) and plasma acetate on day 17 (P<0.05) was observed in C8TG sows. 27903321 10 116 located observed 1779:1786 arg2 concentration 1687:1699 The lowest concentration 1676:1699 The lowest concentration of plasma lactate on day 3 (P<0.05) and plasma acetate on day 17 (P<0.05) 1676:1773 The lowest concentration of plasma lactate on day 3 (P<0.05) and plasma acetate on day 17 (P<0.05) was observed in C8TG sows. 27903321 12 117 theme Feed 1925:1928 arg1 intake 1930:1935 Feed intake 1925:1935 Feed intake 1925:1935 Feed intake tended to be lower (P=0.09), and litter gain during the 3rd week of lactation was decreased (P<0.05) in SBP sows. 27903321 4 118 theme non-starch 653:662 arg1 NSP 681:683 NSP 681:683 NSP 681:683 The SBP diet was high in soluble non-starch polysaccharides (NSP), whereas ALF being high in insoluble NSP. 27903321 4 118 theme non-starch 653:662 arg1 polysaccharides 664:678 soluble non-starch polysaccharides 645:678 soluble non-starch polysaccharides (NSP) 645:684 The SBP diet was high in soluble non-starch polysaccharides (NSP), whereas ALF being high in insoluble NSP. 27903321 6 119 from day 980:982 arg1 sows 970:973 36 second parity sows 953:973 36 second parity sows from day 105 of gestation and throughout lactation 953:1024 Equal amounts of metabolizable energy were fed to 36 second parity sows from day 105 of gestation and throughout lactation to study the impact on feed intake, plasma metabolites, milk production and litter performance. 27903321 0 120 theme dietary 25:31 arg1 fibers 33:38 dietary fibers 25:38 dietary fibers 25:38 Impact of fat source and dietary fibers on feed intake, plasma metabolites, litter gain and the yield and composition of milk in sows. 27903321 6 121 theme second 956:961 arg1 sows 970:973 36 second parity sows 953:973 36 second parity sows from day 105 of gestation and throughout lactation 953:1024 Equal amounts of metabolizable energy were fed to 36 second parity sows from day 105 of gestation and throughout lactation to study the impact on feed intake, plasma metabolites, milk production and litter performance. 27903321 4 122 from high 637:640 arg1 NSP 681:683 NSP 681:683 NSP 681:683 The SBP diet was high in soluble non-starch polysaccharides (NSP), whereas ALF being high in insoluble NSP. 27903321 4 122 from high 637:640 arg1 polysaccharides 664:678 soluble non-starch polysaccharides 645:678 soluble non-starch polysaccharides (NSP) 645:684 The SBP diet was high in soluble non-starch polysaccharides (NSP), whereas ALF being high in insoluble NSP. 27903321 9 123 theme PFAD 1656:1659 arg1 sows 1661:1664 PFAD sows 1656:1664 PFAD sows 1656:1664 Milk protein on days 3 and 10 of lactation were lower in C8TG and SOYO sows, than in PFAD sows (P<0.05). 27903321 2 124 theme feed 283:286 arg1 intake 288:293 feed intake 283:293 feed intake 283:293 Fiber ingredients may reduce feed intake and are often completely excluded from lactation diets, although locally available ingredients may be cost-efficient alternatives to partly replace cereals in lactation diets. 27903321 13 125 theme energy 2166:2171 arg1 intake 2173:2178 reduced energy intake 2158:2178 reduced energy intake in PFAD-fed sows 2158:2195 In conclusion, performance was enhanced in SOYO and C8TG compared with PFAD sows, possibly associated with reduced energy intake in PFAD-fed sows. 27903321 12 126 theme 3rd 1993:1995 arg1 week 1997:2000 the 3rd week 1989:2000 the 3rd week of lactation 1989:2013 Feed intake tended to be lower (P=0.09), and litter gain during the 3rd week of lactation was decreased (P<0.05) in SBP sows. 27903321 10 127 from concentration 1687:1699 arg1 acetate 1748:1754 plasma acetate 1741:1754 plasma acetate on day 17 (P<0.05) 1741:1773 The lowest concentration of plasma lactate on day 3 (P<0.05) and plasma acetate on day 17 (P<0.05) was observed in C8TG sows. 27903321 10 127 from concentration 1687:1699 arg1 day 1722:1724 day 3 1722:1726 day 3 (P<0.05) 1722:1735 The lowest concentration of plasma lactate on day 3 (P<0.05) and plasma acetate on day 17 (P<0.05) was observed in C8TG sows. 27903321 10 127 from concentration 1687:1699 arg1 P<0.05 1729:1734 P<0.05 1729:1734 P<0.05 1729:1734 The lowest concentration of plasma lactate on day 3 (P<0.05) and plasma acetate on day 17 (P<0.05) was observed in C8TG sows. 27903321 10 127 from concentration 1687:1699 arg1 P<0.05 1767:1772 P<0.05 1767:1772 P<0.05 1767:1772 The lowest concentration of plasma lactate on day 3 (P<0.05) and plasma acetate on day 17 (P<0.05) was observed in C8TG sows. 27903321 3 128 theme lactation 488:496 arg1 diet 498:501 a standard lactation diet 477:501 a standard lactation diet low in dietary fiber 477:522 Thus, a standard lactation diet low in dietary fiber, and two high-fiber diets based on sugar beet pulp (SBP) or alfalfa meal (ALF) were formulated. 27903321 3 128 theme lactation 488:496 arg1 SBP 576:578 SBP 576:578 SBP 576:578 Thus, a standard lactation diet low in dietary fiber, and two high-fiber diets based on sugar beet pulp (SBP) or alfalfa meal (ALF) were formulated. 27666402 5 0 theme total 739:743 arg1 proteome 752:759 total plasma proteome 739:759 total plasma proteome 739:759 Here, we studied the N-glycosylation of IgG and total plasma proteome of both maternal and UC plasma of 42 pairs of mothers and newborn children. 27666402 6 1 theme N-glycans 851:859 arg1 total 839:843 A total 837:843 A total of 37 N-glycans 837:859 A total of 37 N-glycans were quantified for IgG and 45 for the total plasma N-glycome (TPNG). 27666402 0 2 link N-linked 34:41 arg1 plasma- 43:49 differential N-linked plasma- 21:49 differential N-linked plasma- 21:49 MALDI-TOF-MS reveals differential N-linked plasma- and IgG-glycosylation profiles between mothers and their newborns. 27666402 9 3 theme plasma 1379:1384 arg1 glycosylation 1386:1398 the differential plasma glycosylation 1362:1398 the differential plasma glycosylation between mothers and newborns 1362:1427 In conclusion, this study presents some novel insights into IgG glycosylation differences as well as the first broad overview of the differential plasma glycosylation between mothers and newborns. 27666402 2 4 from IgG 312:314 arg1 months 353:358 their first months 341:358 their first months 341:358 Newborns depend on maternal IgG for immune-protection in their first months. 27666402 7 5 theme previous 1031:1038 arg1 results 1040:1046 previous results 1031:1046 previous results 1031:1046 The study showed slightly higher levels of galactosylation for UC IgG than maternal IgG, confirming previous results, as well as lower bisection and sialylation. 27666402 9 6 theme differential 1366:1377 arg1 glycosylation 1386:1398 the differential plasma glycosylation 1362:1398 the differential plasma glycosylation between mothers and newborns 1362:1427 In conclusion, this study presents some novel insights into IgG glycosylation differences as well as the first broad overview of the differential plasma glycosylation between mothers and newborns. 27666402 5 7 theme newborn 819:825 arg1 children 827:834 newborn children 819:834 newborn children 819:834 Here, we studied the N-glycosylation of IgG and total plasma proteome of both maternal and UC plasma of 42 pairs of mothers and newborn children. 27666402 5 8 theme mothers 807:813 arg1 pairs 798:802 42 pairs 795:802 42 pairs of mothers and newborn children 795:834 Here, we studied the N-glycosylation of IgG and total plasma proteome of both maternal and UC plasma of 42 pairs of mothers and newborn children. 27666402 8 9 theme lower 1130:1134 arg1 values 1136:1141 lower values 1130:1141 lower values for galactosylation and sialylation 1130:1177 Furthermore, the TPNG results showed lower values for galactosylation and sialylation, and higher values for fucosylation in the UC plasma. 27666402 9 10 theme IgG 1293:1295 arg1 differences 1311:1321 IgG glycosylation differences 1293:1321 IgG glycosylation differences as well as the first broad overview of the differential plasma glycosylation between mothers and newborns 1293:1427 In conclusion, this study presents some novel insights into IgG glycosylation differences as well as the first broad overview of the differential plasma glycosylation between mothers and newborns. 27666402 3 11 theme receptor 433:440 arg1 binding 442:448 receptor binding 433:448 receptor binding 433:448 The glycosylation of IgG has been shown to influence its dynamics, e.g. receptor binding. 27666402 5 12 theme maternal 769:776 arg1 plasma 785:790 both maternal and UC plasma 764:790 both maternal and UC plasma of 42 pairs of mothers and newborn children 764:834 Here, we studied the N-glycosylation of IgG and total plasma proteome of both maternal and UC plasma of 42 pairs of mothers and newborn children. 27666402 4 13 theme IgG 478:480 arg1 glycosylation 482:494 IgG glycosylation 478:494 IgG glycosylation 478:494 While minor differences in IgG glycosylation have been found between IgG derived from maternal blood and umbilical cord blood (UC) of newborn children, the differential glycosylation of maternal and UC plasma has hitherto not been studied. 27666402 4 14 gly glycosylation 620:632 arg1 plasma 653:658 maternal and UC plasma 637:658 maternal and UC plasma 637:658 While minor differences in IgG glycosylation have been found between IgG derived from maternal blood and umbilical cord blood (UC) of newborn children, the differential glycosylation of maternal and UC plasma has hitherto not been studied. 27666402 4 15 theme plasma 653:658 arg1 glycosylation 620:632 the differential glycosylation 603:632 the differential glycosylation of maternal and UC plasma 603:658 While minor differences in IgG glycosylation have been found between IgG derived from maternal blood and umbilical cord blood (UC) of newborn children, the differential glycosylation of maternal and UC plasma has hitherto not been studied. 27666402 6 16 theme plasma 906:911 arg1 N-glycome 913:921 the total plasma N-glycome 896:921 the total plasma N-glycome 896:921 A total of 37 N-glycans were quantified for IgG and 45 for the total plasma N-glycome (TPNG). 27666402 4 17 from differences 463:473 arg1 glycosylation 482:494 IgG glycosylation 478:494 IgG glycosylation 478:494 While minor differences in IgG glycosylation have been found between IgG derived from maternal blood and umbilical cord blood (UC) of newborn children, the differential glycosylation of maternal and UC plasma has hitherto not been studied. 27666402 9 18 theme novel 1273:1277 arg1 insights 1279:1286 some novel insights 1268:1286 some novel insights into IgG glycosylation differences as well as the first broad overview of the differential plasma glycosylation between mothers and newborns 1268:1427 In conclusion, this study presents some novel insights into IgG glycosylation differences as well as the first broad overview of the differential plasma glycosylation between mothers and newborns. 27666402 4 19 attach derived 524:530 arg1 UC 578:579 UC 578:579 UC 578:579 While minor differences in IgG glycosylation have been found between IgG derived from maternal blood and umbilical cord blood (UC) of newborn children, the differential glycosylation of maternal and UC plasma has hitherto not been studied. 27666402 4 19 attach derived 524:530 arg2 IgG 520:522 IgG 520:522 IgG derived from maternal blood and umbilical cord blood (UC) of newborn children 520:600 While minor differences in IgG glycosylation have been found between IgG derived from maternal blood and umbilical cord blood (UC) of newborn children, the differential glycosylation of maternal and UC plasma has hitherto not been studied. 27666402 4 19 attach derived 524:530 arg1 blood 571:575 umbilical cord blood 556:575 umbilical cord blood (UC) 556:580 While minor differences in IgG glycosylation have been found between IgG derived from maternal blood and umbilical cord blood (UC) of newborn children, the differential glycosylation of maternal and UC plasma has hitherto not been studied. 27666402 4 19 attach derived 524:530 arg1 blood 546:550 maternal blood 537:550 maternal blood 537:550 While minor differences in IgG glycosylation have been found between IgG derived from maternal blood and umbilical cord blood (UC) of newborn children, the differential glycosylation of maternal and UC plasma has hitherto not been studied. 27666402 4 20 theme UC 650:651 arg1 plasma 653:658 maternal and UC plasma 637:658 maternal and UC plasma 637:658 While minor differences in IgG glycosylation have been found between IgG derived from maternal blood and umbilical cord blood (UC) of newborn children, the differential glycosylation of maternal and UC plasma has hitherto not been studied. 27666402 0 21 theme N-linked 34:41 arg1 plasma- 43:49 differential N-linked plasma- 21:49 differential N-linked plasma- 21:49 MALDI-TOF-MS reveals differential N-linked plasma- and IgG-glycosylation profiles between mothers and their newborns. 27666402 6 22 theme total 900:904 arg1 N-glycome 913:921 the total plasma N-glycome 896:921 the total plasma N-glycome 896:921 A total of 37 N-glycans were quantified for IgG and 45 for the total plasma N-glycome (TPNG). 27666402 3 23 gly glycosylation 365:377 arg1 IgG 382:384 IgG 382:384 IgG 382:384 The glycosylation of IgG has been shown to influence its dynamics, e.g. receptor binding. 27666402 8 24 theme TPNG 1110:1113 arg1 results 1115:1121 the TPNG results 1106:1121 the TPNG results 1106:1121 Furthermore, the TPNG results showed lower values for galactosylation and sialylation, and higher values for fucosylation in the UC plasma. 27666402 2 25 theme maternal 303:310 arg1 IgG 312:314 maternal IgG 303:314 maternal IgG for immune-protection in their first months 303:358 Newborns depend on maternal IgG for immune-protection in their first months. 27666402 4 26 theme differential 607:618 arg1 glycosylation 620:632 the differential glycosylation 603:632 the differential glycosylation of maternal and UC plasma 603:658 While minor differences in IgG glycosylation have been found between IgG derived from maternal blood and umbilical cord blood (UC) of newborn children, the differential glycosylation of maternal and UC plasma has hitherto not been studied. 27666402 3 27 theme IgG 382:384 arg1 glycosylation 365:377 The glycosylation 361:377 The glycosylation of IgG 361:384 The glycosylation of IgG has been shown to influence its dynamics, e.g. receptor binding. 27666402 4 28 theme cord 566:569 arg1 UC 578:579 UC 578:579 UC 578:579 While minor differences in IgG glycosylation have been found between IgG derived from maternal blood and umbilical cord blood (UC) of newborn children, the differential glycosylation of maternal and UC plasma has hitherto not been studied. 27666402 4 28 theme cord 566:569 arg1 blood 571:575 umbilical cord blood 556:575 umbilical cord blood (UC) 556:580 While minor differences in IgG glycosylation have been found between IgG derived from maternal blood and umbilical cord blood (UC) of newborn children, the differential glycosylation of maternal and UC plasma has hitherto not been studied. 27666402 1 29 theme maternal 210:217 arg1 IgG 237:239 IgG 237:239 IgG 237:239 During pregnancy, the mother provides multiple nutrients and substances to the foetus, with maternal immunoglobulin G (IgG) being actively transported to the foetus. 27666402 1 29 theme maternal 210:217 arg1 G 234:234 maternal immunoglobulin G 210:234 maternal immunoglobulin G (IgG) 210:240 During pregnancy, the mother provides multiple nutrients and substances to the foetus, with maternal immunoglobulin G (IgG) being actively transported to the foetus. 27666402 5 30 theme plasma 745:750 arg1 proteome 752:759 total plasma proteome 739:759 total plasma proteome 739:759 Here, we studied the N-glycosylation of IgG and total plasma proteome of both maternal and UC plasma of 42 pairs of mothers and newborn children. 27666402 4 31 theme umbilical 556:564 arg1 UC 578:579 UC 578:579 UC 578:579 While minor differences in IgG glycosylation have been found between IgG derived from maternal blood and umbilical cord blood (UC) of newborn children, the differential glycosylation of maternal and UC plasma has hitherto not been studied. 27666402 4 31 theme umbilical 556:564 arg1 blood 571:575 umbilical cord blood 556:575 umbilical cord blood (UC) 556:580 While minor differences in IgG glycosylation have been found between IgG derived from maternal blood and umbilical cord blood (UC) of newborn children, the differential glycosylation of maternal and UC plasma has hitherto not been studied. 27666402 7 32 theme galactosylation 974:988 arg1 levels 964:969 slightly higher levels 948:969 slightly higher levels of galactosylation for UC IgG 948:999 The study showed slightly higher levels of galactosylation for UC IgG than maternal IgG, confirming previous results, as well as lower bisection and sialylation. 27666402 5 33 theme pairs 798:802 arg1 plasma 785:790 both maternal and UC plasma 764:790 both maternal and UC plasma of 42 pairs of mothers and newborn children 764:834 Here, we studied the N-glycosylation of IgG and total plasma proteome of both maternal and UC plasma of 42 pairs of mothers and newborn children. 27666402 5 34 theme children 827:834 arg1 pairs 798:802 42 pairs 795:802 42 pairs of mothers and newborn children 795:834 Here, we studied the N-glycosylation of IgG and total plasma proteome of both maternal and UC plasma of 42 pairs of mothers and newborn children. 27666402 1 35 theme immunoglobulin 219:232 arg1 IgG 237:239 IgG 237:239 IgG 237:239 During pregnancy, the mother provides multiple nutrients and substances to the foetus, with maternal immunoglobulin G (IgG) being actively transported to the foetus. 27666402 1 35 theme immunoglobulin 219:232 arg1 G 234:234 maternal immunoglobulin G 210:234 maternal immunoglobulin G (IgG) 210:240 During pregnancy, the mother provides multiple nutrients and substances to the foetus, with maternal immunoglobulin G (IgG) being actively transported to the foetus. 27666402 5 36 theme proteome 752:759 arg1 N-glycosylation 712:726 the N-glycosylation 708:726 the N-glycosylation of IgG and total plasma proteome of both maternal and UC plasma of 42 pairs of mothers and newborn children 708:834 Here, we studied the N-glycosylation of IgG and total plasma proteome of both maternal and UC plasma of 42 pairs of mothers and newborn children. 27666402 4 37 theme minor 457:461 arg1 differences 463:473 minor differences 457:473 minor differences in IgG glycosylation 457:494 While minor differences in IgG glycosylation have been found between IgG derived from maternal blood and umbilical cord blood (UC) of newborn children, the differential glycosylation of maternal and UC plasma has hitherto not been studied. 27666402 5 38 theme UC 782:783 arg1 plasma 785:790 both maternal and UC plasma 764:790 both maternal and UC plasma of 42 pairs of mothers and newborn children 764:834 Here, we studied the N-glycosylation of IgG and total plasma proteome of both maternal and UC plasma of 42 pairs of mothers and newborn children. 27666402 8 39 theme higher 1184:1189 arg1 values 1191:1196 higher values 1184:1196 higher values for fucosylation 1184:1213 Furthermore, the TPNG results showed lower values for galactosylation and sialylation, and higher values for fucosylation in the UC plasma. 27666402 9 40 theme broad 1344:1348 arg1 overview 1350:1357 the first broad overview 1334:1357 IgG glycosylation differences as well as the first broad overview of the differential plasma glycosylation between mothers and newborns 1293:1427 In conclusion, this study presents some novel insights into IgG glycosylation differences as well as the first broad overview of the differential plasma glycosylation between mothers and newborns. 27666402 7 41 dep lower 1060:1064 arg1 bisection 1066:1074 bisection 1066:1074 bisection 1066:1074 The study showed slightly higher levels of galactosylation for UC IgG than maternal IgG, confirming previous results, as well as lower bisection and sialylation. 27666402 9 42 theme first 1338:1342 arg1 overview 1350:1357 the first broad overview 1334:1357 IgG glycosylation differences as well as the first broad overview of the differential plasma glycosylation between mothers and newborns 1293:1427 In conclusion, this study presents some novel insights into IgG glycosylation differences as well as the first broad overview of the differential plasma glycosylation between mothers and newborns. 27666402 2 43 theme first 347:351 arg1 months 353:358 their first months 341:358 their first months 341:358 Newborns depend on maternal IgG for immune-protection in their first months. 27666402 0 44 theme IgG-glycosylation 55:71 arg1 profiles 73:80 IgG-glycosylation profiles 55:80 IgG-glycosylation profiles 55:80 MALDI-TOF-MS reveals differential N-linked plasma- and IgG-glycosylation profiles between mothers and their newborns. 27666402 4 45 theme maternal 537:544 arg1 blood 546:550 maternal blood 537:550 maternal blood 537:550 While minor differences in IgG glycosylation have been found between IgG derived from maternal blood and umbilical cord blood (UC) of newborn children, the differential glycosylation of maternal and UC plasma has hitherto not been studied. 27666402 7 46 theme UC 994:995 arg1 IgG 997:999 UC IgG 994:999 UC IgG 994:999 The study showed slightly higher levels of galactosylation for UC IgG than maternal IgG, confirming previous results, as well as lower bisection and sialylation. 27666402 3 47 dep binding 442:448 arg1 e.g. 428:431 e.g. 428:431 e.g. 428:431 The glycosylation of IgG has been shown to influence its dynamics, e.g. receptor binding. 27666402 5 48 gly N-glycosylation 712:726 arg1 IgG 731:733 IgG 731:733 IgG 731:733 Here, we studied the N-glycosylation of IgG and total plasma proteome of both maternal and UC plasma of 42 pairs of mothers and newborn children. 27666402 5 48 gly N-glycosylation 712:726 arg1 proteome 752:759 total plasma proteome 739:759 total plasma proteome 739:759 Here, we studied the N-glycosylation of IgG and total plasma proteome of both maternal and UC plasma of 42 pairs of mothers and newborn children. 27666402 4 49 theme newborn 585:591 arg1 children 593:600 newborn children 585:600 newborn children 585:600 While minor differences in IgG glycosylation have been found between IgG derived from maternal blood and umbilical cord blood (UC) of newborn children, the differential glycosylation of maternal and UC plasma has hitherto not been studied. 27666402 7 50 theme higher 957:962 arg1 levels 964:969 slightly higher levels 948:969 slightly higher levels of galactosylation for UC IgG 948:999 The study showed slightly higher levels of galactosylation for UC IgG than maternal IgG, confirming previous results, as well as lower bisection and sialylation. 27666402 5 51 theme plasma 785:790 arg1 IgG 731:733 IgG 731:733 IgG 731:733 Here, we studied the N-glycosylation of IgG and total plasma proteome of both maternal and UC plasma of 42 pairs of mothers and newborn children. 27666402 5 51 theme plasma 785:790 arg1 proteome 752:759 total plasma proteome 739:759 total plasma proteome 739:759 Here, we studied the N-glycosylation of IgG and total plasma proteome of both maternal and UC plasma of 42 pairs of mothers and newborn children. 27666402 7 52 theme maternal 1006:1013 arg1 IgG 1015:1017 maternal IgG 1006:1017 maternal IgG 1006:1017 The study showed slightly higher levels of galactosylation for UC IgG than maternal IgG, confirming previous results, as well as lower bisection and sialylation. 27666402 9 53 theme glycosylation 1386:1398 arg1 overview 1350:1357 the first broad overview 1334:1357 IgG glycosylation differences as well as the first broad overview of the differential plasma glycosylation between mothers and newborns 1293:1427 In conclusion, this study presents some novel insights into IgG glycosylation differences as well as the first broad overview of the differential plasma glycosylation between mothers and newborns. 27666402 9 53 theme glycosylation 1386:1398 arg1 differences 1311:1321 IgG glycosylation differences 1293:1321 IgG glycosylation differences as well as the first broad overview of the differential plasma glycosylation between mothers and newborns 1293:1427 In conclusion, this study presents some novel insights into IgG glycosylation differences as well as the first broad overview of the differential plasma glycosylation between mothers and newborns. 27666402 9 54 attach presents 1259:1266 arg1 conclusion 1236:1245 conclusion 1236:1245 conclusion 1236:1245 In conclusion, this study presents some novel insights into IgG glycosylation differences as well as the first broad overview of the differential plasma glycosylation between mothers and newborns. 27666402 9 54 attach presents 1259:1266 arg2 study 1253:1257 this study 1248:1257 this study 1248:1257 In conclusion, this study presents some novel insights into IgG glycosylation differences as well as the first broad overview of the differential plasma glycosylation between mothers and newborns. 27666402 1 55 theme multiple 156:163 arg1 nutrients 165:173 multiple nutrients 156:173 multiple nutrients 156:173 During pregnancy, the mother provides multiple nutrients and substances to the foetus, with maternal immunoglobulin G (IgG) being actively transported to the foetus. 27666402 4 56 theme maternal 637:644 arg1 plasma 653:658 maternal and UC plasma 637:658 maternal and UC plasma 637:658 While minor differences in IgG glycosylation have been found between IgG derived from maternal blood and umbilical cord blood (UC) of newborn children, the differential glycosylation of maternal and UC plasma has hitherto not been studied. 27666402 9 57 theme glycosylation 1297:1309 arg1 differences 1311:1321 IgG glycosylation differences 1293:1321 IgG glycosylation differences as well as the first broad overview of the differential plasma glycosylation between mothers and newborns 1293:1427 In conclusion, this study presents some novel insights into IgG glycosylation differences as well as the first broad overview of the differential plasma glycosylation between mothers and newborns. 27666402 5 58 theme IgG 731:733 arg1 N-glycosylation 712:726 the N-glycosylation 708:726 the N-glycosylation of IgG and total plasma proteome of both maternal and UC plasma of 42 pairs of mothers and newborn children 708:834 Here, we studied the N-glycosylation of IgG and total plasma proteome of both maternal and UC plasma of 42 pairs of mothers and newborn children. 27666402 0 59 theme differential 21:32 arg1 plasma- 43:49 differential N-linked plasma- 21:49 differential N-linked plasma- 21:49 MALDI-TOF-MS reveals differential N-linked plasma- and IgG-glycosylation profiles between mothers and their newborns. 27666402 8 60 theme UC 1222:1223 arg1 plasma 1225:1230 the UC plasma 1218:1230 the UC plasma 1218:1230 Furthermore, the TPNG results showed lower values for galactosylation and sialylation, and higher values for fucosylation in the UC plasma. 27666402 4 61 theme children 593:600 arg1 UC 578:579 UC 578:579 UC 578:579 While minor differences in IgG glycosylation have been found between IgG derived from maternal blood and umbilical cord blood (UC) of newborn children, the differential glycosylation of maternal and UC plasma has hitherto not been studied. 27666402 4 61 theme children 593:600 arg1 blood 571:575 umbilical cord blood 556:575 umbilical cord blood (UC) 556:580 While minor differences in IgG glycosylation have been found between IgG derived from maternal blood and umbilical cord blood (UC) of newborn children, the differential glycosylation of maternal and UC plasma has hitherto not been studied. 27666402 4 61 theme children 593:600 arg1 blood 546:550 maternal blood 537:550 maternal blood 537:550 While minor differences in IgG glycosylation have been found between IgG derived from maternal blood and umbilical cord blood (UC) of newborn children, the differential glycosylation of maternal and UC plasma has hitherto not been studied. 26507522 0 0 theme molecular 78:86 arg1 simulations 97:107 simulations 97:107 simulations 97:107 Understanding the impact of Fc glycosylation on its conformational changes by molecular dynamics simulations and bioinformatics. 26507522 0 0 theme molecular 78:86 arg1 dynamics 88:95 molecular dynamics simulations and bioinformatics 78:126 molecular dynamics simulations and bioinformatics 78:126 Understanding the impact of Fc glycosylation on its conformational changes by molecular dynamics simulations and bioinformatics. 26507522 0 0 theme molecular 78:86 arg1 bioinformatics 113:126 bioinformatics 113:126 bioinformatics 113:126 Understanding the impact of Fc glycosylation on its conformational changes by molecular dynamics simulations and bioinformatics. 26507522 0 1 from impact 18:23 arg1 changes 67:73 its conformational changes 48:73 its conformational changes by molecular dynamics simulations and bioinformatics 48:126 Understanding the impact of Fc glycosylation on its conformational changes by molecular dynamics simulations and bioinformatics. 26507522 5 2 theme " 717:717 arg1 state 719:723 the "open" state 708:723 the "open" state of glycosylated Fc 708:742 However, we could only observe the "open" state of glycosylated Fc. 26507522 8 3 theme key 1049:1051 arg1 Fc 1065:1066 Fc 1065:1066 Fc 1065:1066 Energy decomposition analysis identified key residues of Fc to recognize its two partners P13 and P34. 26507522 8 3 theme key 1049:1051 arg1 residues 1053:1060 key residues 1049:1060 key residues of Fc 1049:1066 Energy decomposition analysis identified key residues of Fc to recognize its two partners P13 and P34. 26507522 2 4 theme Fc 354:355 arg1 glycosylation 357:369 Fc glycosylation 354:369 Fc glycosylation 354:369 Here, we performed all-atom molecular dynamics simulations to explore the effects of Fc glycosylation on its dynamics behaviors. 26507522 8 5 dep partners 1089:1096 arg1 partners 1089:1096 its two partners 1081:1096 its two partners P13 and P34 1081:1108 Energy decomposition analysis identified key residues of Fc to recognize its two partners P13 and P34. 26507522 8 5 dep partners 1089:1096 arg1 P34 1106:1108 P34 1106:1108 P34 1106:1108 Energy decomposition analysis identified key residues of Fc to recognize its two partners P13 and P34. 26507522 8 5 dep partners 1089:1096 arg1 P13 1098:1100 P13 1098:1100 P13 1098:1100 Energy decomposition analysis identified key residues of Fc to recognize its two partners P13 and P34. 26507522 1 6 from N297 161:164 arg1 glycosylation 138:150 N-linked glycosylation 129:150 N-linked glycosylation of Fc at N297 129:164 N-linked glycosylation of Fc at N297 plays an important role in its effector function, aberrance of which would cause disease pathogenesis. 26507522 4 7 theme " 667:667 arg1 states 669:674 "closed" states 660:674 "closed" states 660:674 Besides, the free energy landscape revealed three minimum energy wells in deglycosylated Fc, representing its "open", "semi-closed" and "closed" states. 26507522 11 8 theme deglycosylated 1466:1479 arg1 Fc 1481:1482 deglycosylated Fc 1466:1482 deglycosylated Fc 1466:1482 Collectively, these results together provided the structural basis for understanding conformational changes of deglycosylated Fc and the recognition mechanism of the Fc binding to its partners. 26507522 1 9 theme disease 247:253 arg1 pathogenesis 255:266 disease pathogenesis 247:266 disease pathogenesis 247:266 N-linked glycosylation of Fc at N297 plays an important role in its effector function, aberrance of which would cause disease pathogenesis. 26507522 6 10 theme principal 759:767 arg1 analysis 779:786 principal component analysis 759:786 principal component analysis 759:786 Supportively, principal component analysis emphasized the prominent motion of delyclosylated Fc and dynamically depicted how it changed from the "open" state to its "closed" state. 26507522 4 11 theme semi-closed 643:653 arg1 " 654:654 "semi-closed" 642:654 "semi-closed" 642:654 Besides, the free energy landscape revealed three minimum energy wells in deglycosylated Fc, representing its "open", "semi-closed" and "closed" states. 26507522 4 12 theme deglycosylated 598:611 arg1 Fc 613:614 deglycosylated Fc 598:614 deglycosylated Fc 598:614 Besides, the free energy landscape revealed three minimum energy wells in deglycosylated Fc, representing its "open", "semi-closed" and "closed" states. 26507522 4 13 theme closed 661:666 arg1 states 669:674 "closed" states 660:674 "closed" states 660:674 Besides, the free energy landscape revealed three minimum energy wells in deglycosylated Fc, representing its "open", "semi-closed" and "closed" states. 26507522 2 14 from effects 343:349 arg1 behaviors 387:395 its dynamics behaviors 374:395 its dynamics behaviors 374:395 Here, we performed all-atom molecular dynamics simulations to explore the effects of Fc glycosylation on its dynamics behaviors. 26507522 3 15 theme CH2 512:514 arg1 domain 516:521 its CH2 domain 508:521 its CH2 domain 508:521 Firstly, equilibrium simulations suggested that Fc deglycosylation was able to induce residual flexibility in its CH2 domain. 26507522 6 16 theme " 917:917 arg1 state 919:923 its "closed" state 906:923 its "closed" state 906:923 Supportively, principal component analysis emphasized the prominent motion of delyclosylated Fc and dynamically depicted how it changed from the "open" state to its "closed" state. 26507522 4 17 from wells 589:593 arg1 Fc 613:614 deglycosylated Fc 598:614 deglycosylated Fc 598:614 Besides, the free energy landscape revealed three minimum energy wells in deglycosylated Fc, representing its "open", "semi-closed" and "closed" states. 26507522 3 18 theme Fc 446:447 arg1 deglycosylation 449:463 Fc deglycosylation 446:463 Fc deglycosylation 446:463 Firstly, equilibrium simulations suggested that Fc deglycosylation was able to induce residual flexibility in its CH2 domain. 26507522 3 19 theme equilibrium 407:417 arg1 simulations 419:429 equilibrium simulations 407:429 equilibrium simulations 407:429 Firstly, equilibrium simulations suggested that Fc deglycosylation was able to induce residual flexibility in its CH2 domain. 26507522 0 20 dep dynamics 88:95 arg1 simulations 97:107 simulations 97:107 simulations 97:107 Understanding the impact of Fc glycosylation on its conformational changes by molecular dynamics simulations and bioinformatics. 26507522 0 20 dep dynamics 88:95 arg1 dynamics 88:95 molecular dynamics simulations and bioinformatics 78:126 molecular dynamics simulations and bioinformatics 78:126 Understanding the impact of Fc glycosylation on its conformational changes by molecular dynamics simulations and bioinformatics. 26507522 0 20 dep dynamics 88:95 arg1 bioinformatics 113:126 bioinformatics 113:126 bioinformatics 113:126 Understanding the impact of Fc glycosylation on its conformational changes by molecular dynamics simulations and bioinformatics. 26507522 1 21 theme important 175:183 arg1 role 185:188 an important role 172:188 an important role 172:188 N-linked glycosylation of Fc at N297 plays an important role in its effector function, aberrance of which would cause disease pathogenesis. 26507522 11 22 gly deglycosylated 1466:1479 arg1 Fc 1481:1482 deglycosylated Fc 1466:1482 deglycosylated Fc 1466:1482 Collectively, these results together provided the structural basis for understanding conformational changes of deglycosylated Fc and the recognition mechanism of the Fc binding to its partners. 26507522 9 23 theme electrostatic 1122:1134 arg1 surfaces 1146:1153 electrostatic potential surfaces 1122:1153 electrostatic potential surfaces 1122:1153 Evidently, electrostatic potential surfaces showed that electrostatic attraction helped to stabilize the interaction between Fc and its partners. 26507522 2 24 theme dynamics 378:385 arg1 behaviors 387:395 its dynamics behaviors 374:395 its dynamics behaviors 374:395 Here, we performed all-atom molecular dynamics simulations to explore the effects of Fc glycosylation on its dynamics behaviors. 26507522 8 25 theme decomposition 1015:1027 arg1 analysis 1029:1036 Energy decomposition analysis 1008:1036 Energy decomposition analysis 1008:1036 Energy decomposition analysis identified key residues of Fc to recognize its two partners P13 and P34. 26507522 6 26 theme closed 911:916 arg1 state 919:923 its "closed" state 906:923 its "closed" state 906:923 Supportively, principal component analysis emphasized the prominent motion of delyclosylated Fc and dynamically depicted how it changed from the "open" state to its "closed" state. 26507522 9 27 theme potential 1136:1144 arg1 surfaces 1146:1153 electrostatic potential surfaces 1122:1153 electrostatic potential surfaces 1122:1153 Evidently, electrostatic potential surfaces showed that electrostatic attraction helped to stabilize the interaction between Fc and its partners. 26507522 2 28 theme dynamics 307:314 arg1 simulations 316:326 all-atom molecular dynamics simulations 288:326 all-atom molecular dynamics simulations 288:326 Here, we performed all-atom molecular dynamics simulations to explore the effects of Fc glycosylation on its dynamics behaviors. 26507522 11 29 theme Fc 1521:1522 arg1 binding 1524:1530 the Fc binding 1517:1530 the Fc binding to its partners 1517:1546 Collectively, these results together provided the structural basis for understanding conformational changes of deglycosylated Fc and the recognition mechanism of the Fc binding to its partners. 26507522 2 30 gly glycosylation 357:369 arg1 dynamics 378:385 its dynamics behaviors 374:395 its dynamics behaviors 374:395 Here, we performed all-atom molecular dynamics simulations to explore the effects of Fc glycosylation on its dynamics behaviors. 26507522 4 31 gly deglycosylated 598:611 arg1 Fc 613:614 deglycosylated Fc 598:614 deglycosylated Fc 598:614 Besides, the free energy landscape revealed three minimum energy wells in deglycosylated Fc, representing its "open", "semi-closed" and "closed" states. 26507522 2 32 theme molecular 297:305 arg1 simulations 316:326 all-atom molecular dynamics simulations 288:326 all-atom molecular dynamics simulations 288:326 Here, we performed all-atom molecular dynamics simulations to explore the effects of Fc glycosylation on its dynamics behaviors. 26507522 6 33 theme component 769:777 arg1 analysis 779:786 principal component analysis 759:786 principal component analysis 759:786 Supportively, principal component analysis emphasized the prominent motion of delyclosylated Fc and dynamically depicted how it changed from the "open" state to its "closed" state. 26507522 4 34 theme open 635:638 arg1 " 639:639 its "open" 630:639 its "open" 630:639 Besides, the free energy landscape revealed three minimum energy wells in deglycosylated Fc, representing its "open", "semi-closed" and "closed" states. 26507522 4 35 theme minimum 574:580 arg1 wells 589:593 three minimum energy wells 568:593 three minimum energy wells in deglycosylated Fc 568:614 Besides, the free energy landscape revealed three minimum energy wells in deglycosylated Fc, representing its "open", "semi-closed" and "closed" states. 26507522 6 36 theme Fc 838:839 arg1 motion 813:818 the prominent motion 799:818 the prominent motion of delyclosylated Fc 799:839 Supportively, principal component analysis emphasized the prominent motion of delyclosylated Fc and dynamically depicted how it changed from the "open" state to its "closed" state. 26507522 2 37 theme all-atom 288:295 arg1 simulations 316:326 all-atom molecular dynamics simulations 288:326 all-atom molecular dynamics simulations 288:326 Here, we performed all-atom molecular dynamics simulations to explore the effects of Fc glycosylation on its dynamics behaviors. 26507522 4 38 theme energy 582:587 arg1 wells 589:593 three minimum energy wells 568:593 three minimum energy wells in deglycosylated Fc 568:614 Besides, the free energy landscape revealed three minimum energy wells in deglycosylated Fc, representing its "open", "semi-closed" and "closed" states. 26507522 1 39 theme effector 197:204 arg1 function 206:213 its effector function 193:213 its effector function 193:213 N-linked glycosylation of Fc at N297 plays an important role in its effector function, aberrance of which would cause disease pathogenesis. 26507522 0 40 theme glycosylation 31:43 arg1 impact 18:23 the impact 14:23 the impact of Fc glycosylation on its conformational changes by molecular dynamics simulations and bioinformatics 14:126 Understanding the impact of Fc glycosylation on its conformational changes by molecular dynamics simulations and bioinformatics. 26507522 10 41 from affinities 1322:1331 arg1 Fc-P13 1336:1341 Fc-P13 1336:1341 Fc-P13 1336:1341 Also, relative binding free energies explained different binding affinities in Fc-P13 and Fc-P34. 26507522 10 41 from affinities 1322:1331 arg1 Fc-P34 1347:1352 Fc-P34 1347:1352 Fc-P34 1347:1352 Also, relative binding free energies explained different binding affinities in Fc-P13 and Fc-P34. 26507522 7 42 theme Fc 980:981 arg1 binding 983:989 the Fc binding 976:989 the Fc binding to its partners 976:1005 Secondly, we studied the recognition mechanism of the Fc binding to its partners. 26507522 6 43 theme delyclosylated 823:836 arg1 Fc 838:839 delyclosylated Fc 823:839 delyclosylated Fc 823:839 Supportively, principal component analysis emphasized the prominent motion of delyclosylated Fc and dynamically depicted how it changed from the "open" state to its "closed" state. 26507522 11 44 theme structural 1405:1414 arg1 basis 1416:1420 the structural basis 1401:1420 the structural basis for understanding conformational changes of deglycosylated Fc 1401:1482 Collectively, these results together provided the structural basis for understanding conformational changes of deglycosylated Fc and the recognition mechanism of the Fc binding to its partners. 26507522 1 45 theme function 206:213 arg1 aberrance 216:224 aberrance 216:224 aberrance 216:224 N-linked glycosylation of Fc at N297 plays an important role in its effector function, aberrance of which would cause disease pathogenesis. 26507522 0 46 theme Fc 28:29 arg1 glycosylation 31:43 Fc glycosylation 28:43 Fc glycosylation 28:43 Understanding the impact of Fc glycosylation on its conformational changes by molecular dynamics simulations and bioinformatics. 26507522 1 47 gly glycosylation 138:150 arg2 N297 161:164 N297 161:164 N297 161:164 N-linked glycosylation of Fc at N297 plays an important role in its effector function, aberrance of which would cause disease pathogenesis. 26507522 1 47 gly glycosylation 138:150 arg1 N297 161:164 N297 161:164 N297 161:164 N-linked glycosylation of Fc at N297 plays an important role in its effector function, aberrance of which would cause disease pathogenesis. 26507522 1 47 gly glycosylation 138:150 arg1 Fc 155:156 Fc 155:156 Fc 155:156 N-linked glycosylation of Fc at N297 plays an important role in its effector function, aberrance of which would cause disease pathogenesis. 26507522 9 48 theme electrostatic 1167:1179 arg1 attraction 1181:1190 electrostatic attraction 1167:1190 electrostatic attraction 1167:1190 Evidently, electrostatic potential surfaces showed that electrostatic attraction helped to stabilize the interaction between Fc and its partners. 26507522 10 49 theme free 1280:1283 arg1 energies 1285:1292 relative binding free energies 1263:1292 relative binding free energies 1263:1292 Also, relative binding free energies explained different binding affinities in Fc-P13 and Fc-P34. 26507522 5 50 theme Fc 741:742 arg1 state 719:723 the "open" state 708:723 the "open" state of glycosylated Fc 708:742 However, we could only observe the "open" state of glycosylated Fc. 26507522 6 51 theme " 895:895 arg1 state 897:901 the "open" state 886:901 the "open" state 886:901 Supportively, principal component analysis emphasized the prominent motion of delyclosylated Fc and dynamically depicted how it changed from the "open" state to its "closed" state. 26507522 5 52 theme open 713:716 arg1 state 719:723 the "open" state 708:723 the "open" state of glycosylated Fc 708:742 However, we could only observe the "open" state of glycosylated Fc. 26507522 10 53 theme binding 1272:1278 arg1 energies 1285:1292 relative binding free energies 1263:1292 relative binding free energies 1263:1292 Also, relative binding free energies explained different binding affinities in Fc-P13 and Fc-P34. 26507522 7 54 theme binding 983:989 arg1 mechanism 963:971 the recognition mechanism 947:971 the recognition mechanism of the Fc binding to its partners 947:1005 Secondly, we studied the recognition mechanism of the Fc binding to its partners. 26507522 6 55 theme open 891:894 arg1 state 897:901 the "open" state 886:901 the "open" state 886:901 Supportively, principal component analysis emphasized the prominent motion of delyclosylated Fc and dynamically depicted how it changed from the "open" state to its "closed" state. 26507522 4 56 theme energy 542:547 arg1 landscape 549:557 the free energy landscape 533:557 the free energy landscape 533:557 Besides, the free energy landscape revealed three minimum energy wells in deglycosylated Fc, representing its "open", "semi-closed" and "closed" states. 26507522 6 57 theme prominent 803:811 arg1 motion 813:818 the prominent motion 799:818 the prominent motion of delyclosylated Fc 799:839 Supportively, principal component analysis emphasized the prominent motion of delyclosylated Fc and dynamically depicted how it changed from the "open" state to its "closed" state. 26507522 10 58 theme relative 1263:1270 arg1 energies 1285:1292 relative binding free energies 1263:1292 relative binding free energies 1263:1292 Also, relative binding free energies explained different binding affinities in Fc-P13 and Fc-P34. 26507522 1 59 theme N-linked 129:136 arg1 glycosylation 138:150 N-linked glycosylation 129:150 N-linked glycosylation of Fc at N297 129:164 N-linked glycosylation of Fc at N297 plays an important role in its effector function, aberrance of which would cause disease pathogenesis. 26507522 4 60 theme free 537:540 arg1 landscape 549:557 the free energy landscape 533:557 the free energy landscape 533:557 Besides, the free energy landscape revealed three minimum energy wells in deglycosylated Fc, representing its "open", "semi-closed" and "closed" states. 26507522 7 61 theme recognition 951:961 arg1 mechanism 963:971 the recognition mechanism 947:971 the recognition mechanism of the Fc binding to its partners 947:1005 Secondly, we studied the recognition mechanism of the Fc binding to its partners. 26507522 5 62 gly glycosylated 728:739 arg1 Fc 741:742 glycosylated Fc 728:742 glycosylated Fc 728:742 However, we could only observe the "open" state of glycosylated Fc. 26507522 3 63 theme residual 484:491 arg1 flexibility 493:503 residual flexibility 484:503 residual flexibility 484:503 Firstly, equilibrium simulations suggested that Fc deglycosylation was able to induce residual flexibility in its CH2 domain. 26507522 11 64 theme binding 1524:1530 arg1 basis 1416:1420 the structural basis 1401:1420 the structural basis for understanding conformational changes of deglycosylated Fc 1401:1482 Collectively, these results together provided the structural basis for understanding conformational changes of deglycosylated Fc and the recognition mechanism of the Fc binding to its partners. 26507522 11 64 theme binding 1524:1530 arg1 mechanism 1504:1512 the recognition mechanism 1488:1512 the recognition mechanism of the Fc binding to its partners 1488:1546 Collectively, these results together provided the structural basis for understanding conformational changes of deglycosylated Fc and the recognition mechanism of the Fc binding to its partners. 26507522 1 65 link N-linked 129:136 arg1 glycosylation 138:150 N-linked glycosylation 129:150 N-linked glycosylation of Fc at N297 129:164 N-linked glycosylation of Fc at N297 plays an important role in its effector function, aberrance of which would cause disease pathogenesis. 26507522 10 66 theme binding 1314:1320 arg1 affinities 1322:1331 different binding affinities 1304:1331 different binding affinities in Fc-P13 and Fc-P34 1304:1352 Also, relative binding free energies explained different binding affinities in Fc-P13 and Fc-P34. 26507522 11 67 theme recognition 1492:1502 arg1 mechanism 1504:1512 the recognition mechanism 1488:1512 the recognition mechanism of the Fc binding to its partners 1488:1546 Collectively, these results together provided the structural basis for understanding conformational changes of deglycosylated Fc and the recognition mechanism of the Fc binding to its partners. 26507522 8 68 theme Fc 1065:1066 arg1 Fc 1065:1066 Fc 1065:1066 Fc 1065:1066 Energy decomposition analysis identified key residues of Fc to recognize its two partners P13 and P34. 26507522 8 68 theme Fc 1065:1066 arg1 residues 1053:1060 key residues 1049:1060 key residues of Fc 1049:1066 Energy decomposition analysis identified key residues of Fc to recognize its two partners P13 and P34. 26507522 11 69 theme Fc 1481:1482 arg1 changes 1455:1461 conformational changes 1440:1461 conformational changes of deglycosylated Fc 1440:1482 Collectively, these results together provided the structural basis for understanding conformational changes of deglycosylated Fc and the recognition mechanism of the Fc binding to its partners. 26507522 10 70 theme different 1304:1312 arg1 affinities 1322:1331 different binding affinities 1304:1331 different binding affinities in Fc-P13 and Fc-P34 1304:1352 Also, relative binding free energies explained different binding affinities in Fc-P13 and Fc-P34. 26507522 1 71 theme Fc 155:156 arg1 glycosylation 138:150 N-linked glycosylation 129:150 N-linked glycosylation of Fc at N297 129:164 N-linked glycosylation of Fc at N297 plays an important role in its effector function, aberrance of which would cause disease pathogenesis. 26507522 11 72 theme conformational 1440:1453 arg1 changes 1455:1461 conformational changes 1440:1461 conformational changes of deglycosylated Fc 1440:1482 Collectively, these results together provided the structural basis for understanding conformational changes of deglycosylated Fc and the recognition mechanism of the Fc binding to its partners. 26507522 0 73 theme conformational 52:65 arg1 changes 67:73 its conformational changes 48:73 its conformational changes by molecular dynamics simulations and bioinformatics 48:126 Understanding the impact of Fc glycosylation on its conformational changes by molecular dynamics simulations and bioinformatics. 26507522 5 74 theme glycosylated 728:739 arg1 Fc 741:742 glycosylated Fc 728:742 glycosylated Fc 728:742 However, we could only observe the "open" state of glycosylated Fc. 26507522 2 75 theme glycosylation 357:369 arg1 effects 343:349 the effects 339:349 the effects of Fc glycosylation on its dynamics behaviors 339:395 Here, we performed all-atom molecular dynamics simulations to explore the effects of Fc glycosylation on its dynamics behaviors. 26507522 8 76 theme Energy 1008:1013 arg1 analysis 1029:1036 Energy decomposition analysis 1008:1036 Energy decomposition analysis 1008:1036 Energy decomposition analysis identified key residues of Fc to recognize its two partners P13 and P34. 24810879 0 0 theme units 92:96 arg1 repeats 68:74 repeats 68:74 repeats of proline-type units 68:96 Synthesis and folding propensity of aliphatic oligoureas containing repeats of proline-type units. 24810879 2 1 theme oligourea 333:341 arg1 N 321:321 N 321:321 N 321:321 The insertion of trisubstituted ureas in the main chain of N,N'-linked oligourea foldamers locally impairs the characteristic three centered-hydrogen bonding pattern associated with the formation of 2.5-helical structures. 24810879 2 1 theme oligourea 333:341 arg1 foldamers 343:351 N'-linked oligourea foldamers 323:351 N'-linked oligourea foldamers 323:351 The insertion of trisubstituted ureas in the main chain of N,N'-linked oligourea foldamers locally impairs the characteristic three centered-hydrogen bonding pattern associated with the formation of 2.5-helical structures. 24810879 3 2 theme u 782:782 arg1 oligomers 795:803 oligomers 25 and 26 795:813 oligomers 25 and 26 795:813 Three series of oligomers have been studied: one series in which the Pro(u) repeat is flanked on both sides by canonical urea residues (e.g., oligomers 2-6), one series with canonical residues on either side of the Pro(u) repeat (oligomers 12 and 23), and one series consisting exclusively of Pro(u) residues (oligomers 25 and 26). 24810879 3 2 theme u 782:782 arg1 residues 785:792 Pro(u) residues 778:792 Pro(u) residues (oligomers 25 and 26) 778:814 Three series of oligomers have been studied: one series in which the Pro(u) repeat is flanked on both sides by canonical urea residues (e.g., oligomers 2-6), one series with canonical residues on either side of the Pro(u) repeat (oligomers 12 and 23), and one series consisting exclusively of Pro(u) residues (oligomers 25 and 26). 24810879 0 3 theme proline-type 79:90 arg1 units 92:96 proline-type units 79:96 proline-type units 79:96 Synthesis and folding propensity of aliphatic oligoureas containing repeats of proline-type units. 24810879 1 4 theme adjacent 185:192 arg1 units 206:210 multiple adjacent N-alkylated units 176:210 multiple adjacent N-alkylated units derived from proline (i.e., Pro(u)) 176:246 The synthesis and conformational analysis of aliphatic oligoureas containing multiple adjacent N-alkylated units derived from proline (i.e., Pro(u)) are reported. 24810879 3 5 with series 647:652 arg1 residues 669:676 canonical residues 659:676 canonical residues on either side of the Pro(u) repeat (oligomers 12 and 23) 659:734 Three series of oligomers have been studied: one series in which the Pro(u) repeat is flanked on both sides by canonical urea residues (e.g., oligomers 2-6), one series with canonical residues on either side of the Pro(u) repeat (oligomers 12 and 23), and one series consisting exclusively of Pro(u) residues (oligomers 25 and 26). 24810879 3 6 dep oligomers 627:635 arg1 e.g. 621:624 e.g. 621:624 e.g. 621:624 Three series of oligomers have been studied: one series in which the Pro(u) repeat is flanked on both sides by canonical urea residues (e.g., oligomers 2-6), one series with canonical residues on either side of the Pro(u) repeat (oligomers 12 and 23), and one series consisting exclusively of Pro(u) residues (oligomers 25 and 26). 24810879 4 7 theme Spectroscopic 817:829 arg1 studies 893:899 Spectroscopic (NMR and electronic circular dichroism) and X-ray diffraction studies 817:899 Spectroscopic (NMR and electronic circular dichroism) and X-ray diffraction studies 817:899 Spectroscopic (NMR and electronic circular dichroism) and X-ray diffraction studies reveal that the 2.5-helix formed by oligomers of N,N'-disubstituted ureas is robust enough to accommodate short oligopyrrolidine segments (Pro(u))n (n < 7) that alone display no intrinsic folding propensity. 24810879 2 8 theme N'-linked 323:331 arg1 N 321:321 N 321:321 N 321:321 The insertion of trisubstituted ureas in the main chain of N,N'-linked oligourea foldamers locally impairs the characteristic three centered-hydrogen bonding pattern associated with the formation of 2.5-helical structures. 24810879 2 8 theme N'-linked 323:331 arg1 foldamers 343:351 N'-linked oligourea foldamers 323:351 N'-linked oligourea foldamers 323:351 The insertion of trisubstituted ureas in the main chain of N,N'-linked oligourea foldamers locally impairs the characteristic three centered-hydrogen bonding pattern associated with the formation of 2.5-helical structures. 24810879 2 9 theme trisubstituted 279:292 arg1 ureas 294:298 trisubstituted ureas 279:298 trisubstituted ureas 279:298 The insertion of trisubstituted ureas in the main chain of N,N'-linked oligourea foldamers locally impairs the characteristic three centered-hydrogen bonding pattern associated with the formation of 2.5-helical structures. 24810879 3 10 theme Pro 778:780 arg1 oligomers 795:803 oligomers 25 and 26 795:813 oligomers 25 and 26 795:813 Three series of oligomers have been studied: one series in which the Pro(u) repeat is flanked on both sides by canonical urea residues (e.g., oligomers 2-6), one series with canonical residues on either side of the Pro(u) repeat (oligomers 12 and 23), and one series consisting exclusively of Pro(u) residues (oligomers 25 and 26). 24810879 3 10 theme Pro 778:780 arg1 residues 785:792 Pro(u) residues 778:792 Pro(u) residues (oligomers 25 and 26) 778:814 Three series of oligomers have been studied: one series in which the Pro(u) repeat is flanked on both sides by canonical urea residues (e.g., oligomers 2-6), one series with canonical residues on either side of the Pro(u) repeat (oligomers 12 and 23), and one series consisting exclusively of Pro(u) residues (oligomers 25 and 26). 24810879 3 11 theme u 558:558 arg1 repeat 561:566 the Pro(u) repeat 550:566 the Pro(u) repeat 550:566 Three series of oligomers have been studied: one series in which the Pro(u) repeat is flanked on both sides by canonical urea residues (e.g., oligomers 2-6), one series with canonical residues on either side of the Pro(u) repeat (oligomers 12 and 23), and one series consisting exclusively of Pro(u) residues (oligomers 25 and 26). 24810879 1 12 theme multiple 176:183 arg1 units 206:210 multiple adjacent N-alkylated units 176:210 multiple adjacent N-alkylated units derived from proline (i.e., Pro(u)) 176:246 The synthesis and conformational analysis of aliphatic oligoureas containing multiple adjacent N-alkylated units derived from proline (i.e., Pro(u)) are reported. 24810879 4 13 theme short 1007:1011 arg1 segments 1030:1037 short oligopyrrolidine segments 1007:1037 short oligopyrrolidine segments (Pro(u)) 1007:1046 Spectroscopic (NMR and electronic circular dichroism) and X-ray diffraction studies reveal that the 2.5-helix formed by oligomers of N,N'-disubstituted ureas is robust enough to accommodate short oligopyrrolidine segments (Pro(u))n (n < 7) that alone display no intrinsic folding propensity. 24810879 2 14 link N'-linked 323:331 arg1 N 321:321 N 321:321 N 321:321 The insertion of trisubstituted ureas in the main chain of N,N'-linked oligourea foldamers locally impairs the characteristic three centered-hydrogen bonding pattern associated with the formation of 2.5-helical structures. 24810879 2 14 link N'-linked 323:331 arg1 foldamers 343:351 N'-linked oligourea foldamers 323:351 N'-linked oligourea foldamers 323:351 The insertion of trisubstituted ureas in the main chain of N,N'-linked oligourea foldamers locally impairs the characteristic three centered-hydrogen bonding pattern associated with the formation of 2.5-helical structures. 24810879 1 15 theme N-alkylated 194:204 arg1 units 206:210 multiple adjacent N-alkylated units 176:210 multiple adjacent N-alkylated units derived from proline (i.e., Pro(u)) 176:246 The synthesis and conformational analysis of aliphatic oligoureas containing multiple adjacent N-alkylated units derived from proline (i.e., Pro(u)) are reported. 24810879 2 16 theme 2.5-helical 461:471 arg1 structures 473:482 2.5-helical structures 461:482 2.5-helical structures 461:482 The insertion of trisubstituted ureas in the main chain of N,N'-linked oligourea foldamers locally impairs the characteristic three centered-hydrogen bonding pattern associated with the formation of 2.5-helical structures. 24810879 1 17 contain containing 165:174 arg2 units 206:210 multiple adjacent N-alkylated units 176:210 multiple adjacent N-alkylated units derived from proline (i.e., Pro(u)) 176:246 The synthesis and conformational analysis of aliphatic oligoureas containing multiple adjacent N-alkylated units derived from proline (i.e., Pro(u)) are reported. 24810879 1 17 contain containing 165:174 arg1 oligoureas 154:163 aliphatic oligoureas 144:163 aliphatic oligoureas containing multiple adjacent N-alkylated units derived from proline (i.e., Pro(u)) 144:246 The synthesis and conformational analysis of aliphatic oligoureas containing multiple adjacent N-alkylated units derived from proline (i.e., Pro(u)) are reported. 24810879 4 18 theme n 1050:1050 arg1 < 1052:1052 n < 7 1050:1054 n < 7 1050:1054 Spectroscopic (NMR and electronic circular dichroism) and X-ray diffraction studies reveal that the 2.5-helix formed by oligomers of N,N'-disubstituted ureas is robust enough to accommodate short oligopyrrolidine segments (Pro(u))n (n < 7) that alone display no intrinsic folding propensity. 24810879 3 19 theme oligomers 501:509 arg1 series 491:496 Three series 485:496 Three series of oligomers 485:509 Three series of oligomers have been studied: one series in which the Pro(u) repeat is flanked on both sides by canonical urea residues (e.g., oligomers 2-6), one series with canonical residues on either side of the Pro(u) repeat (oligomers 12 and 23), and one series consisting exclusively of Pro(u) residues (oligomers 25 and 26). 24810879 2 20 theme characteristic 373:386 arg1 pattern 420:426 the characteristic three centered-hydrogen bonding pattern 369:426 the characteristic three centered-hydrogen bonding pattern associated with the formation of 2.5-helical structures 369:482 The insertion of trisubstituted ureas in the main chain of N,N'-linked oligourea foldamers locally impairs the characteristic three centered-hydrogen bonding pattern associated with the formation of 2.5-helical structures. 24810879 4 21 theme circular 851:858 arg1 dichroism 860:868 electronic circular dichroism 840:868 electronic circular dichroism 840:868 Spectroscopic (NMR and electronic circular dichroism) and X-ray diffraction studies reveal that the 2.5-helix formed by oligomers of N,N'-disubstituted ureas is robust enough to accommodate short oligopyrrolidine segments (Pro(u))n (n < 7) that alone display no intrinsic folding propensity. 24810879 2 22 theme main 307:310 arg1 chain 312:316 the main chain 303:316 the main chain of N,N'-linked oligourea foldamers 303:351 The insertion of trisubstituted ureas in the main chain of N,N'-linked oligourea foldamers locally impairs the characteristic three centered-hydrogen bonding pattern associated with the formation of 2.5-helical structures. 24810879 3 23 with series 745:750 arg1 residues 669:676 canonical residues 659:676 canonical residues on either side of the Pro(u) repeat (oligomers 12 and 23) 659:734 Three series of oligomers have been studied: one series in which the Pro(u) repeat is flanked on both sides by canonical urea residues (e.g., oligomers 2-6), one series with canonical residues on either side of the Pro(u) repeat (oligomers 12 and 23), and one series consisting exclusively of Pro(u) residues (oligomers 25 and 26). 24810879 3 24 from residues 669:676 arg1 side 688:691 either side 681:691 either side of the Pro(u) repeat (oligomers 12 and 23) 681:734 Three series of oligomers have been studied: one series in which the Pro(u) repeat is flanked on both sides by canonical urea residues (e.g., oligomers 2-6), one series with canonical residues on either side of the Pro(u) repeat (oligomers 12 and 23), and one series consisting exclusively of Pro(u) residues (oligomers 25 and 26). 24810879 3 25 dep studied 521:527 arg1 series 534:539 one series 530:539 one series in which the Pro(u) repeat is flanked on both sides by canonical urea residues (e.g., oligomers 2-6), one series with canonical residues on either side of the Pro(u) repeat (oligomers 12 and 23), and one series consisting exclusively of Pro(u) residues (oligomers 25 and 26) 530:814 Three series of oligomers have been studied: one series in which the Pro(u) repeat is flanked on both sides by canonical urea residues (e.g., oligomers 2-6), one series with canonical residues on either side of the Pro(u) repeat (oligomers 12 and 23), and one series consisting exclusively of Pro(u) residues (oligomers 25 and 26). 24810879 4 26 dep n 1047:1047 arg1 robust 978:983 robust 978:983 robust 978:983 Spectroscopic (NMR and electronic circular dichroism) and X-ray diffraction studies reveal that the 2.5-helix formed by oligomers of N,N'-disubstituted ureas is robust enough to accommodate short oligopyrrolidine segments (Pro(u))n (n < 7) that alone display no intrinsic folding propensity. 24810879 4 26 dep n 1047:1047 arg1 < 1052:1052 n < 7 1050:1054 n < 7 1050:1054 Spectroscopic (NMR and electronic circular dichroism) and X-ray diffraction studies reveal that the 2.5-helix formed by oligomers of N,N'-disubstituted ureas is robust enough to accommodate short oligopyrrolidine segments (Pro(u))n (n < 7) that alone display no intrinsic folding propensity. 24810879 3 27 theme Pro 700:702 arg1 oligomers 715:723 oligomers 12 and 23 715:733 oligomers 715:723 Three series of oligomers have been studied: one series in which the Pro(u) repeat is flanked on both sides by canonical urea residues (e.g., oligomers 2-6), one series with canonical residues on either side of the Pro(u) repeat (oligomers 12 and 23), and one series consisting exclusively of Pro(u) residues (oligomers 25 and 26). 24810879 3 27 theme Pro 700:702 arg1 23 732:733 23 732:733 23 732:733 Three series of oligomers have been studied: one series in which the Pro(u) repeat is flanked on both sides by canonical urea residues (e.g., oligomers 2-6), one series with canonical residues on either side of the Pro(u) repeat (oligomers 12 and 23), and one series consisting exclusively of Pro(u) residues (oligomers 25 and 26). 24810879 3 27 theme Pro 700:702 arg1 repeat 707:712 the Pro(u) repeat 696:712 the Pro(u) repeat (oligomers 12 and 23) 696:734 Three series of oligomers have been studied: one series in which the Pro(u) repeat is flanked on both sides by canonical urea residues (e.g., oligomers 2-6), one series with canonical residues on either side of the Pro(u) repeat (oligomers 12 and 23), and one series consisting exclusively of Pro(u) residues (oligomers 25 and 26). 24810879 3 28 theme Pro 554:556 arg1 repeat 561:566 the Pro(u) repeat 550:566 the Pro(u) repeat 550:566 Three series of oligomers have been studied: one series in which the Pro(u) repeat is flanked on both sides by canonical urea residues (e.g., oligomers 2-6), one series with canonical residues on either side of the Pro(u) repeat (oligomers 12 and 23), and one series consisting exclusively of Pro(u) residues (oligomers 25 and 26). 24810879 3 29 with residues 611:618 arg1 residues 669:676 canonical residues 659:676 canonical residues on either side of the Pro(u) repeat (oligomers 12 and 23) 659:734 Three series of oligomers have been studied: one series in which the Pro(u) repeat is flanked on both sides by canonical urea residues (e.g., oligomers 2-6), one series with canonical residues on either side of the Pro(u) repeat (oligomers 12 and 23), and one series consisting exclusively of Pro(u) residues (oligomers 25 and 26). 24810879 2 30 theme ureas 294:298 arg1 insertion 266:274 The insertion 262:274 The insertion of trisubstituted ureas in the main chain of N,N'-linked oligourea foldamers 262:351 The insertion of trisubstituted ureas in the main chain of N,N'-linked oligourea foldamers locally impairs the characteristic three centered-hydrogen bonding pattern associated with the formation of 2.5-helical structures. 24810879 3 31 theme urea 606:609 arg1 residues 611:618 canonical urea residues 596:618 canonical urea residues (e.g., oligomers 2-6) 596:640 Three series of oligomers have been studied: one series in which the Pro(u) repeat is flanked on both sides by canonical urea residues (e.g., oligomers 2-6), one series with canonical residues on either side of the Pro(u) repeat (oligomers 12 and 23), and one series consisting exclusively of Pro(u) residues (oligomers 25 and 26). 24810879 1 32 theme oligoureas 154:163 arg1 synthesis 103:111 synthesis 103:111 synthesis 103:111 The synthesis and conformational analysis of aliphatic oligoureas containing multiple adjacent N-alkylated units derived from proline (i.e., Pro(u)) are reported. 24810879 1 32 theme oligoureas 154:163 arg1 analysis 132:139 conformational analysis 117:139 conformational analysis 117:139 The synthesis and conformational analysis of aliphatic oligoureas containing multiple adjacent N-alkylated units derived from proline (i.e., Pro(u)) are reported. 24810879 0 33 theme aliphatic 36:44 arg1 oligoureas 46:55 aliphatic oligoureas 36:55 aliphatic oligoureas 36:55 Synthesis and folding propensity of aliphatic oligoureas containing repeats of proline-type units. 24810879 4 34 dep Spectroscopic 817:829 arg1 NMR 832:834 NMR 832:834 NMR 832:834 Spectroscopic (NMR and electronic circular dichroism) and X-ray diffraction studies reveal that the 2.5-helix formed by oligomers of N,N'-disubstituted ureas is robust enough to accommodate short oligopyrrolidine segments (Pro(u))n (n < 7) that alone display no intrinsic folding propensity. 24810879 4 34 dep Spectroscopic 817:829 arg1 dichroism 860:868 electronic circular dichroism 840:868 electronic circular dichroism 840:868 Spectroscopic (NMR and electronic circular dichroism) and X-ray diffraction studies reveal that the 2.5-helix formed by oligomers of N,N'-disubstituted ureas is robust enough to accommodate short oligopyrrolidine segments (Pro(u))n (n < 7) that alone display no intrinsic folding propensity. 24810879 2 35 theme bonding 412:418 arg1 pattern 420:426 the characteristic three centered-hydrogen bonding pattern 369:426 the characteristic three centered-hydrogen bonding pattern associated with the formation of 2.5-helical structures 369:482 The insertion of trisubstituted ureas in the main chain of N,N'-linked oligourea foldamers locally impairs the characteristic three centered-hydrogen bonding pattern associated with the formation of 2.5-helical structures. 24810879 4 36 theme N 950:950 arg1 oligomers 937:945 oligomers 937:945 oligomers of N,N'-disubstituted ureas 937:973 Spectroscopic (NMR and electronic circular dichroism) and X-ray diffraction studies reveal that the 2.5-helix formed by oligomers of N,N'-disubstituted ureas is robust enough to accommodate short oligopyrrolidine segments (Pro(u))n (n < 7) that alone display no intrinsic folding propensity. 24810879 4 37 theme X-ray 875:879 arg1 diffraction 881:891 X-ray diffraction 875:891 X-ray diffraction 875:891 Spectroscopic (NMR and electronic circular dichroism) and X-ray diffraction studies reveal that the 2.5-helix formed by oligomers of N,N'-disubstituted ureas is robust enough to accommodate short oligopyrrolidine segments (Pro(u))n (n < 7) that alone display no intrinsic folding propensity. 24810879 1 38 dep Pro 240:242 arg1 i.e. 234:237 i.e. 234:237 i.e. 234:237 The synthesis and conformational analysis of aliphatic oligoureas containing multiple adjacent N-alkylated units derived from proline (i.e., Pro(u)) are reported. 24810879 4 39 dep segments 1030:1037 arg1 Pro 1040:1042 Pro 1040:1042 Pro(u) 1040:1045 Spectroscopic (NMR and electronic circular dichroism) and X-ray diffraction studies reveal that the 2.5-helix formed by oligomers of N,N'-disubstituted ureas is robust enough to accommodate short oligopyrrolidine segments (Pro(u))n (n < 7) that alone display no intrinsic folding propensity. 24810879 4 39 dep segments 1030:1037 arg1 u 1044:1044 u 1044:1044 u 1044:1044 Spectroscopic (NMR and electronic circular dichroism) and X-ray diffraction studies reveal that the 2.5-helix formed by oligomers of N,N'-disubstituted ureas is robust enough to accommodate short oligopyrrolidine segments (Pro(u))n (n < 7) that alone display no intrinsic folding propensity. 24810879 2 40 theme centered-hydrogen 394:410 arg1 pattern 420:426 the characteristic three centered-hydrogen bonding pattern 369:426 the characteristic three centered-hydrogen bonding pattern associated with the formation of 2.5-helical structures 369:482 The insertion of trisubstituted ureas in the main chain of N,N'-linked oligourea foldamers locally impairs the characteristic three centered-hydrogen bonding pattern associated with the formation of 2.5-helical structures. 24810879 2 41 theme structures 473:482 arg1 formation 448:456 the formation 444:456 the formation of 2.5-helical structures 444:482 The insertion of trisubstituted ureas in the main chain of N,N'-linked oligourea foldamers locally impairs the characteristic three centered-hydrogen bonding pattern associated with the formation of 2.5-helical structures. 24810879 3 42 theme repeat 707:712 arg1 side 688:691 either side 681:691 either side of the Pro(u) repeat (oligomers 12 and 23) 681:734 Three series of oligomers have been studied: one series in which the Pro(u) repeat is flanked on both sides by canonical urea residues (e.g., oligomers 2-6), one series with canonical residues on either side of the Pro(u) repeat (oligomers 12 and 23), and one series consisting exclusively of Pro(u) residues (oligomers 25 and 26). 24810879 1 43 attach derived 212:218 arg1 proline 225:231 proline 225:231 proline (i.e., Pro(u)) 225:246 The synthesis and conformational analysis of aliphatic oligoureas containing multiple adjacent N-alkylated units derived from proline (i.e., Pro(u)) are reported. 24810879 1 43 attach derived 212:218 arg2 units 206:210 multiple adjacent N-alkylated units 176:210 multiple adjacent N-alkylated units derived from proline (i.e., Pro(u)) 176:246 The synthesis and conformational analysis of aliphatic oligoureas containing multiple adjacent N-alkylated units derived from proline (i.e., Pro(u)) are reported. 24810879 3 44 theme canonical 659:667 arg1 residues 669:676 canonical residues 659:676 canonical residues on either side of the Pro(u) repeat (oligomers 12 and 23) 659:734 Three series of oligomers have been studied: one series in which the Pro(u) repeat is flanked on both sides by canonical urea residues (e.g., oligomers 2-6), one series with canonical residues on either side of the Pro(u) repeat (oligomers 12 and 23), and one series consisting exclusively of Pro(u) residues (oligomers 25 and 26). 24810879 1 45 theme conformational 117:130 arg1 analysis 132:139 conformational analysis 117:139 conformational analysis 117:139 The synthesis and conformational analysis of aliphatic oligoureas containing multiple adjacent N-alkylated units derived from proline (i.e., Pro(u)) are reported. 24810879 0 46 theme oligoureas 46:55 arg1 folding 14:20 folding 14:20 folding 14:20 Synthesis and folding propensity of aliphatic oligoureas containing repeats of proline-type units. 24810879 0 46 theme oligoureas 46:55 arg1 Synthesis 0:8 Synthesis 0:8 Synthesis 0:8 Synthesis and folding propensity of aliphatic oligoureas containing repeats of proline-type units. 24810879 4 47 theme intrinsic 1079:1087 arg1 propensity 1097:1106 no intrinsic folding propensity 1076:1106 no intrinsic folding propensity 1076:1106 Spectroscopic (NMR and electronic circular dichroism) and X-ray diffraction studies reveal that the 2.5-helix formed by oligomers of N,N'-disubstituted ureas is robust enough to accommodate short oligopyrrolidine segments (Pro(u))n (n < 7) that alone display no intrinsic folding propensity. 24810879 2 48 theme N 321:321 arg1 chain 312:316 the main chain 303:316 the main chain of N,N'-linked oligourea foldamers 303:351 The insertion of trisubstituted ureas in the main chain of N,N'-linked oligourea foldamers locally impairs the characteristic three centered-hydrogen bonding pattern associated with the formation of 2.5-helical structures. 24810879 2 49 from insertion 266:274 arg1 chain 312:316 the main chain 303:316 the main chain of N,N'-linked oligourea foldamers 303:351 The insertion of trisubstituted ureas in the main chain of N,N'-linked oligourea foldamers locally impairs the characteristic three centered-hydrogen bonding pattern associated with the formation of 2.5-helical structures. 24810879 3 50 theme u 704:704 arg1 oligomers 715:723 oligomers 12 and 23 715:733 oligomers 715:723 Three series of oligomers have been studied: one series in which the Pro(u) repeat is flanked on both sides by canonical urea residues (e.g., oligomers 2-6), one series with canonical residues on either side of the Pro(u) repeat (oligomers 12 and 23), and one series consisting exclusively of Pro(u) residues (oligomers 25 and 26). 24810879 3 50 theme u 704:704 arg1 23 732:733 23 732:733 23 732:733 Three series of oligomers have been studied: one series in which the Pro(u) repeat is flanked on both sides by canonical urea residues (e.g., oligomers 2-6), one series with canonical residues on either side of the Pro(u) repeat (oligomers 12 and 23), and one series consisting exclusively of Pro(u) residues (oligomers 25 and 26). 24810879 3 50 theme u 704:704 arg1 repeat 707:712 the Pro(u) repeat 696:712 the Pro(u) repeat (oligomers 12 and 23) 696:734 Three series of oligomers have been studied: one series in which the Pro(u) repeat is flanked on both sides by canonical urea residues (e.g., oligomers 2-6), one series with canonical residues on either side of the Pro(u) repeat (oligomers 12 and 23), and one series consisting exclusively of Pro(u) residues (oligomers 25 and 26). 24810879 3 51 theme canonical 596:604 arg1 residues 611:618 canonical urea residues 596:618 canonical urea residues (e.g., oligomers 2-6) 596:640 Three series of oligomers have been studied: one series in which the Pro(u) repeat is flanked on both sides by canonical urea residues (e.g., oligomers 2-6), one series with canonical residues on either side of the Pro(u) repeat (oligomers 12 and 23), and one series consisting exclusively of Pro(u) residues (oligomers 25 and 26). 24810879 1 52 theme aliphatic 144:152 arg1 oligoureas 154:163 aliphatic oligoureas 144:163 aliphatic oligoureas containing multiple adjacent N-alkylated units derived from proline (i.e., Pro(u)) 144:246 The synthesis and conformational analysis of aliphatic oligoureas containing multiple adjacent N-alkylated units derived from proline (i.e., Pro(u)) are reported. 24810879 4 53 theme N'-disubstituted 952:967 arg1 N 950:950 N 950:950 N 950:950 Spectroscopic (NMR and electronic circular dichroism) and X-ray diffraction studies reveal that the 2.5-helix formed by oligomers of N,N'-disubstituted ureas is robust enough to accommodate short oligopyrrolidine segments (Pro(u))n (n < 7) that alone display no intrinsic folding propensity. 24810879 4 53 theme N'-disubstituted 952:967 arg1 ureas 969:973 N'-disubstituted ureas 952:973 N'-disubstituted ureas 952:973 Spectroscopic (NMR and electronic circular dichroism) and X-ray diffraction studies reveal that the 2.5-helix formed by oligomers of N,N'-disubstituted ureas is robust enough to accommodate short oligopyrrolidine segments (Pro(u))n (n < 7) that alone display no intrinsic folding propensity. 24810879 4 54 theme oligopyrrolidine 1013:1028 arg1 segments 1030:1037 short oligopyrrolidine segments 1007:1037 short oligopyrrolidine segments (Pro(u)) 1007:1046 Spectroscopic (NMR and electronic circular dichroism) and X-ray diffraction studies reveal that the 2.5-helix formed by oligomers of N,N'-disubstituted ureas is robust enough to accommodate short oligopyrrolidine segments (Pro(u))n (n < 7) that alone display no intrinsic folding propensity. 24810879 4 55 theme electronic 840:849 arg1 dichroism 860:868 electronic circular dichroism 840:868 electronic circular dichroism 840:868 Spectroscopic (NMR and electronic circular dichroism) and X-ray diffraction studies reveal that the 2.5-helix formed by oligomers of N,N'-disubstituted ureas is robust enough to accommodate short oligopyrrolidine segments (Pro(u))n (n < 7) that alone display no intrinsic folding propensity. 24810879 4 56 theme folding 1089:1095 arg1 propensity 1097:1106 no intrinsic folding propensity 1076:1106 no intrinsic folding propensity 1076:1106 Spectroscopic (NMR and electronic circular dichroism) and X-ray diffraction studies reveal that the 2.5-helix formed by oligomers of N,N'-disubstituted ureas is robust enough to accommodate short oligopyrrolidine segments (Pro(u))n (n < 7) that alone display no intrinsic folding propensity. 24810879 1 57 dep proline 225:231 arg1 u 244:244 u 244:244 u 244:244 The synthesis and conformational analysis of aliphatic oligoureas containing multiple adjacent N-alkylated units derived from proline (i.e., Pro(u)) are reported. 24810879 1 57 dep proline 225:231 arg1 Pro 240:242 Pro 240:242 Pro(u) 240:245 The synthesis and conformational analysis of aliphatic oligoureas containing multiple adjacent N-alkylated units derived from proline (i.e., Pro(u)) are reported. 24810879 1 58 dep synthesis 103:111 arg1 The 99:101 The 99:101 The 99:101 The synthesis and conformational analysis of aliphatic oligoureas containing multiple adjacent N-alkylated units derived from proline (i.e., Pro(u)) are reported. 24810879 4 59 theme diffraction 881:891 arg1 studies 893:899 Spectroscopic (NMR and electronic circular dichroism) and X-ray diffraction studies 817:899 Spectroscopic (NMR and electronic circular dichroism) and X-ray diffraction studies 817:899 Spectroscopic (NMR and electronic circular dichroism) and X-ray diffraction studies reveal that the 2.5-helix formed by oligomers of N,N'-disubstituted ureas is robust enough to accommodate short oligopyrrolidine segments (Pro(u))n (n < 7) that alone display no intrinsic folding propensity. 24810879 0 60 dep Synthesis 0:8 arg1 propensity 22:31 propensity 22:31 propensity 22:31 Synthesis and folding propensity of aliphatic oligoureas containing repeats of proline-type units. 28802580 11 0 theme pluripotency 1290:1301 arg1 maintenance 1275:1285 the maintenance 1271:1285 the maintenance of pluripotency 1271:1301 Overall, our data suggest that OGT-mediated O-GlcNAcylation of BAP1 prefers the maintenance of pluripotency, whereas its inhibition facilitates RA-induced differentiation in ES cells. 28802580 5 1 theme BAP1 521:524 arg1 O-GlcNAcylation 502:516 The O-GlcNAcylation 498:516 The O-GlcNAcylation 498:516 The O-GlcNAcylation of BAP1, which requires OGT, was examined in vivo and in vitro, and was proven using alloxan, an OGT inhibitor. 28802580 1 2 theme diverse 142:148 arg1 functions 161:169 diverse biological functions 142:169 diverse biological functions 142:169 BRCA1-associated protein 1 (BAP1) has been implicated in diverse biological functions, including tumor suppression. 28802580 1 2 theme diverse 142:148 arg1 suppression 188:198 tumor suppression 182:198 tumor suppression 182:198 BRCA1-associated protein 1 (BAP1) has been implicated in diverse biological functions, including tumor suppression. 28802580 6 3 dep -induced 692:699 arg1 acid 683:686 retinoic acid 674:686 retinoic acid 674:686 OGT promoted the BAP1-induced repression of retinoic acid (RA)-induced RA receptor (RAR) activation. 28802580 10 4 theme bodies 1137:1142 arg1 expression 1152:1161 the expression 1148:1161 the expression of Sox2, a pluripotency marker 1148:1192 This cooperation was also observed by measuring the size of embryonic bodies and the expression of Sox2, a pluripotency marker. 28802580 10 4 theme bodies 1137:1142 arg1 size 1119:1122 the size 1115:1122 the size of embryonic bodies 1115:1142 This cooperation was also observed by measuring the size of embryonic bodies and the expression of Sox2, a pluripotency marker. 28802580 0 5 from role 12:15 arg1 signaling 74:82 retinoic acid signaling 60:82 retinoic acid signaling 60:82 Suppressive role of OGT-mediated O-GlcNAcylation of BAP1 in retinoic acid signaling. 28802580 8 6 theme cells 943:947 arg1 differentiation 914:928 the RA-induced differentiation 899:928 the RA-induced differentiation of murine ES cells 899:947 Finally, we addressed the role of O-GlcNAcylation in the RA-induced differentiation of murine ES cells. 28802580 1 7 theme biological 150:159 arg1 functions 161:169 diverse biological functions 142:169 diverse biological functions 142:169 BRCA1-associated protein 1 (BAP1) has been implicated in diverse biological functions, including tumor suppression. 28802580 1 7 theme biological 150:159 arg1 suppression 188:198 tumor suppression 182:198 tumor suppression 182:198 BRCA1-associated protein 1 (BAP1) has been implicated in diverse biological functions, including tumor suppression. 28802580 10 8 theme embryonic 1127:1135 arg1 bodies 1137:1142 embryonic bodies 1127:1142 embryonic bodies 1127:1142 This cooperation was also observed by measuring the size of embryonic bodies and the expression of Sox2, a pluripotency marker. 28802580 11 9 theme RA-induced 1339:1348 arg1 differentiation 1350:1364 RA-induced differentiation 1339:1364 RA-induced differentiation in ES cells 1339:1376 Overall, our data suggest that OGT-mediated O-GlcNAcylation of BAP1 prefers the maintenance of pluripotency, whereas its inhibition facilitates RA-induced differentiation in ES cells. 28802580 5 10 theme OGT 615:617 arg1 alloxan 603:609 alloxan 603:609 alloxan 603:609 The O-GlcNAcylation of BAP1, which requires OGT, was examined in vivo and in vitro, and was proven using alloxan, an OGT inhibitor. 28802580 5 10 theme OGT 615:617 arg1 inhibitor 619:627 an OGT inhibitor 612:627 an OGT inhibitor 612:627 The O-GlcNAcylation of BAP1, which requires OGT, was examined in vivo and in vitro, and was proven using alloxan, an OGT inhibitor. 28802580 8 11 theme O-GlcNAcylation 880:894 arg1 role 872:875 the role 868:875 the role of O-GlcNAcylation in the RA-induced differentiation of murine ES cells 868:947 Finally, we addressed the role of O-GlcNAcylation in the RA-induced differentiation of murine ES cells. 28802580 2 12 theme ES 275:276 arg1 cells 279:283 embryonic stem (ES) cells 259:283 embryonic stem (ES) cells 259:283 However, its regulation via glycosylation and its role in embryonic stem (ES) cells are poorly defined. 28802580 10 13 theme Sox2 1166:1169 arg1 expression 1152:1161 the expression 1148:1161 the expression of Sox2, a pluripotency marker 1148:1192 This cooperation was also observed by measuring the size of embryonic bodies and the expression of Sox2, a pluripotency marker. 28802580 10 13 theme Sox2 1166:1169 arg1 size 1119:1122 the size 1115:1122 the size of embryonic bodies 1115:1142 This cooperation was also observed by measuring the size of embryonic bodies and the expression of Sox2, a pluripotency marker. 28802580 9 14 theme ES 1057:1058 arg1 cells 1060:1064 ES cells 1057:1064 ES cells 1057:1064 Alkaline phosphatase staining revealed the cooperation of RA and alloxan for impairing the pluripotency of ES cells. 28802580 8 15 theme RA-induced 903:912 arg1 differentiation 914:928 the RA-induced differentiation 899:928 the RA-induced differentiation of murine ES cells 899:947 Finally, we addressed the role of O-GlcNAcylation in the RA-induced differentiation of murine ES cells. 28802580 2 16 from regulation 214:223 arg1 cells 279:283 embryonic stem (ES) cells 259:283 embryonic stem (ES) cells 259:283 However, its regulation via glycosylation and its role in embryonic stem (ES) cells are poorly defined. 28802580 9 17 theme alloxan 1015:1021 arg1 cooperation 993:1003 the cooperation 989:1003 the cooperation of RA and alloxan for impairing the pluripotency of ES cells 989:1064 Alkaline phosphatase staining revealed the cooperation of RA and alloxan for impairing the pluripotency of ES cells. 28802580 4 18 theme physical 431:438 arg1 interaction 440:450 the physical interaction 427:450 the physical interaction 427:450 Here, we confirmed the physical interaction and investigated its functional significance. 28802580 7 19 theme O-GlcNAcase 817:827 arg1 PUGNAc 806:811 PUGNAc 806:811 PUGNAc 806:811 The repressive activity of BAP1 was relieved by alloxan but exacerbated by PUGNAc, an O-GlcNAcase (OGA) inhibitor. 28802580 7 19 theme O-GlcNAcase 817:827 arg1 inhibitor 835:843 an O-GlcNAcase (OGA) inhibitor 814:843 an O-GlcNAcase (OGA) inhibitor 814:843 The repressive activity of BAP1 was relieved by alloxan but exacerbated by PUGNAc, an O-GlcNAcase (OGA) inhibitor. 28802580 2 20 theme stem 269:272 arg1 cells 279:283 embryonic stem (ES) cells 259:283 embryonic stem (ES) cells 259:283 However, its regulation via glycosylation and its role in embryonic stem (ES) cells are poorly defined. 28802580 9 21 theme RA 1008:1009 arg1 cooperation 993:1003 the cooperation 989:1003 the cooperation of RA and alloxan for impairing the pluripotency of ES cells 989:1064 Alkaline phosphatase staining revealed the cooperation of RA and alloxan for impairing the pluripotency of ES cells. 28802580 2 22 theme embryonic 259:267 arg1 cells 279:283 embryonic stem (ES) cells 259:283 embryonic stem (ES) cells 259:283 However, its regulation via glycosylation and its role in embryonic stem (ES) cells are poorly defined. 28802580 3 23 theme N-acetylglucosamine 358:376 arg1 OGT 402:404 OGT 402:404 OGT 402:404 BAP1 was recently reported to interact with O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT). 28802580 3 23 theme N-acetylglucosamine 358:376 arg1 transferase 389:399 O-linked N-acetylglucosamine (O-GlcNAc) transferase 349:399 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) 349:405 BAP1 was recently reported to interact with O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT). 28802580 6 24 theme activation 719:728 arg1 repression 660:669 the BAP1-induced repression 643:669 the BAP1-induced repression of retinoic acid (RA)-induced RA receptor (RAR) activation 643:728 OGT promoted the BAP1-induced repression of retinoic acid (RA)-induced RA receptor (RAR) activation. 28802580 1 25 theme BRCA1-associated 85:100 arg1 protein 102:108 BRCA1-associated protein 1 85:110 BRCA1-associated protein 1 (BAP1) 85:117 BRCA1-associated protein 1 (BAP1) has been implicated in diverse biological functions, including tumor suppression. 28802580 1 25 theme BRCA1-associated 85:100 arg1 BAP1 113:116 BAP1 113:116 BAP1 113:116 BRCA1-associated protein 1 (BAP1) has been implicated in diverse biological functions, including tumor suppression. 28802580 6 26 theme BAP1-induced 647:658 arg1 repression 660:669 the BAP1-induced repression 643:669 the BAP1-induced repression of retinoic acid (RA)-induced RA receptor (RAR) activation 643:728 OGT promoted the BAP1-induced repression of retinoic acid (RA)-induced RA receptor (RAR) activation. 28802580 0 27 theme Suppressive 0:10 arg1 role 12:15 Suppressive role 0:15 Suppressive role of OGT-mediated O-GlcNAcylation of BAP1 in retinoic acid signaling. 0:83 Suppressive role of OGT-mediated O-GlcNAcylation of BAP1 in retinoic acid signaling. 28802580 8 28 theme ES 940:941 arg1 cells 943:947 murine ES cells 933:947 murine ES cells 933:947 Finally, we addressed the role of O-GlcNAcylation in the RA-induced differentiation of murine ES cells. 28802580 1 29 theme tumor 182:186 arg1 suppression 188:198 tumor suppression 182:198 tumor suppression 182:198 BRCA1-associated protein 1 (BAP1) has been implicated in diverse biological functions, including tumor suppression. 28802580 0 30 theme OGT-mediated 20:31 arg1 O-GlcNAcylation 33:47 OGT-mediated O-GlcNAcylation 20:47 OGT-mediated O-GlcNAcylation of BAP1 20:55 Suppressive role of OGT-mediated O-GlcNAcylation of BAP1 in retinoic acid signaling. 28802580 8 31 theme murine 933:938 arg1 cells 943:947 murine ES cells 933:947 murine ES cells 933:947 Finally, we addressed the role of O-GlcNAcylation in the RA-induced differentiation of murine ES cells. 28802580 3 32 theme O-linked 349:356 arg1 N-acetylglucosamine 358:376 O-linked N-acetylglucosamine 349:376 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) 349:405 BAP1 was recently reported to interact with O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT). 28802580 3 32 theme O-linked 349:356 arg1 O-GlcNAc 379:386 O-GlcNAc 379:386 O-GlcNAc 379:386 BAP1 was recently reported to interact with O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT). 28802580 9 33 theme cells 1060:1064 arg1 pluripotency 1041:1052 the pluripotency 1037:1052 the pluripotency of ES cells 1037:1064 Alkaline phosphatase staining revealed the cooperation of RA and alloxan for impairing the pluripotency of ES cells. 28802580 7 34 theme BAP1 758:761 arg1 relieved 767:774 relieved 767:774 relieved by alloxan 767:785 The repressive activity of BAP1 was relieved by alloxan but exacerbated by PUGNAc, an O-GlcNAcase (OGA) inhibitor. 28802580 7 34 theme BAP1 758:761 arg1 activity 746:753 The repressive activity 731:753 The repressive activity of BAP1 731:761 The repressive activity of BAP1 was relieved by alloxan but exacerbated by PUGNAc, an O-GlcNAcase (OGA) inhibitor. 28802580 8 35 from role 872:875 arg1 differentiation 914:928 the RA-induced differentiation 899:928 the RA-induced differentiation of murine ES cells 899:947 Finally, we addressed the role of O-GlcNAcylation in the RA-induced differentiation of murine ES cells. 28802580 7 36 theme repressive 735:744 arg1 relieved 767:774 relieved 767:774 relieved by alloxan 767:785 The repressive activity of BAP1 was relieved by alloxan but exacerbated by PUGNAc, an O-GlcNAcase (OGA) inhibitor. 28802580 7 36 theme repressive 735:744 arg1 activity 746:753 The repressive activity 731:753 The repressive activity of BAP1 731:761 The repressive activity of BAP1 was relieved by alloxan but exacerbated by PUGNAc, an O-GlcNAcase (OGA) inhibitor. 28802580 2 37 from role 251:254 arg1 cells 279:283 embryonic stem (ES) cells 259:283 embryonic stem (ES) cells 259:283 However, its regulation via glycosylation and its role in embryonic stem (ES) cells are poorly defined. 28802580 0 38 theme O-GlcNAcylation 33:47 arg1 role 12:15 Suppressive role 0:15 Suppressive role of OGT-mediated O-GlcNAcylation of BAP1 in retinoic acid signaling. 0:83 Suppressive role of OGT-mediated O-GlcNAcylation of BAP1 in retinoic acid signaling. 28802580 11 39 theme OGT-mediated 1226:1237 arg1 O-GlcNAcylation 1239:1253 OGT-mediated O-GlcNAcylation 1226:1253 OGT-mediated O-GlcNAcylation of BAP1 1226:1261 Overall, our data suggest that OGT-mediated O-GlcNAcylation of BAP1 prefers the maintenance of pluripotency, whereas its inhibition facilitates RA-induced differentiation in ES cells. 28802580 11 40 from differentiation 1350:1364 arg1 cells 1372:1376 ES cells 1369:1376 ES cells 1369:1376 Overall, our data suggest that OGT-mediated O-GlcNAcylation of BAP1 prefers the maintenance of pluripotency, whereas its inhibition facilitates RA-induced differentiation in ES cells. 28802580 6 41 theme receptor 704:711 arg1 activation 719:728 retinoic acid (RA)-induced RA receptor (RAR) activation 674:728 retinoic acid (RA)-induced RA receptor (RAR) activation 674:728 OGT promoted the BAP1-induced repression of retinoic acid (RA)-induced RA receptor (RAR) activation. 28802580 0 42 theme BAP1 52:55 arg1 O-GlcNAcylation 33:47 OGT-mediated O-GlcNAcylation 20:47 OGT-mediated O-GlcNAcylation of BAP1 20:55 Suppressive role of OGT-mediated O-GlcNAcylation of BAP1 in retinoic acid signaling. 28802580 11 43 theme ES 1369:1370 arg1 cells 1372:1376 ES cells 1369:1376 ES cells 1369:1376 Overall, our data suggest that OGT-mediated O-GlcNAcylation of BAP1 prefers the maintenance of pluripotency, whereas its inhibition facilitates RA-induced differentiation in ES cells. 28802580 11 44 theme BAP1 1258:1261 arg1 O-GlcNAcylation 1239:1253 OGT-mediated O-GlcNAcylation 1226:1253 OGT-mediated O-GlcNAcylation of BAP1 1226:1261 Overall, our data suggest that OGT-mediated O-GlcNAcylation of BAP1 prefers the maintenance of pluripotency, whereas its inhibition facilitates RA-induced differentiation in ES cells. 28802580 6 45 theme RA 701:702 arg1 RAR 714:716 RAR 714:716 RAR 714:716 OGT promoted the BAP1-induced repression of retinoic acid (RA)-induced RA receptor (RAR) activation. 28802580 6 45 theme RA 701:702 arg1 receptor 704:711 RA receptor 701:711 retinoic acid (RA)-induced RA receptor (RAR) activation 674:728 OGT promoted the BAP1-induced repression of retinoic acid (RA)-induced RA receptor (RAR) activation. 28802580 6 46 theme -induced 692:699 arg1 activation 719:728 retinoic acid (RA)-induced RA receptor (RAR) activation 674:728 retinoic acid (RA)-induced RA receptor (RAR) activation 674:728 OGT promoted the BAP1-induced repression of retinoic acid (RA)-induced RA receptor (RAR) activation. 28802580 3 47 link O-linked 349:356 arg1 N-acetylglucosamine 358:376 O-linked N-acetylglucosamine 349:376 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) 349:405 BAP1 was recently reported to interact with O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT). 28802580 3 47 link O-linked 349:356 arg1 O-GlcNAc 379:386 O-GlcNAc 379:386 O-GlcNAc 379:386 BAP1 was recently reported to interact with O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT). 28802580 9 48 theme Alkaline 950:957 arg1 phosphatase 959:969 Alkaline phosphatase 950:969 Alkaline phosphatase staining 950:978 Alkaline phosphatase staining revealed the cooperation of RA and alloxan for impairing the pluripotency of ES cells. 28802580 0 49 theme acid 69:72 arg1 signaling 74:82 retinoic acid signaling 60:82 retinoic acid signaling 60:82 Suppressive role of OGT-mediated O-GlcNAcylation of BAP1 in retinoic acid signaling. 28802580 10 50 theme pluripotency 1174:1185 arg1 marker 1187:1192 a pluripotency marker 1172:1192 a pluripotency marker 1172:1192 This cooperation was also observed by measuring the size of embryonic bodies and the expression of Sox2, a pluripotency marker. 28802580 10 50 theme pluripotency 1174:1185 arg1 Sox2 1166:1169 Sox2 1166:1169 Sox2 1166:1169 This cooperation was also observed by measuring the size of embryonic bodies and the expression of Sox2, a pluripotency marker. 28802580 7 51 theme OGA 830:832 arg1 PUGNAc 806:811 PUGNAc 806:811 PUGNAc 806:811 The repressive activity of BAP1 was relieved by alloxan but exacerbated by PUGNAc, an O-GlcNAcase (OGA) inhibitor. 28802580 7 51 theme OGA 830:832 arg1 inhibitor 835:843 an O-GlcNAcase (OGA) inhibitor 814:843 an O-GlcNAcase (OGA) inhibitor 814:843 The repressive activity of BAP1 was relieved by alloxan but exacerbated by PUGNAc, an O-GlcNAcase (OGA) inhibitor. 28802580 0 52 theme retinoic 60:67 arg1 signaling 74:82 retinoic acid signaling 60:82 retinoic acid signaling 60:82 Suppressive role of OGT-mediated O-GlcNAcylation of BAP1 in retinoic acid signaling. 28802580 4 53 theme functional 473:482 arg1 significance 484:495 its functional significance 469:495 its functional significance 469:495 Here, we confirmed the physical interaction and investigated its functional significance. 28802580 9 54 theme phosphatase 959:969 arg1 staining 971:978 Alkaline phosphatase staining 950:978 Alkaline phosphatase staining 950:978 Alkaline phosphatase staining revealed the cooperation of RA and alloxan for impairing the pluripotency of ES cells. 28802580 6 55 theme retinoic 674:681 arg1 acid 683:686 retinoic acid 674:686 retinoic acid 674:686 OGT promoted the BAP1-induced repression of retinoic acid (RA)-induced RA receptor (RAR) activation. 28630345 4 0 theme glycan-binding 722:735 arg1 proteins 737:744 several glycan-binding proteins 714:744 several glycan-binding proteins uncovered that not only terminal glycoepitopes but also complex architectures of glycans can influence binding selectivity in unanticipated manners 714:892 Probing the array with several glycan-binding proteins uncovered that not only terminal glycoepitopes but also complex architectures of glycans can influence binding selectivity in unanticipated manners. 28630345 4 1 theme complex 802:808 arg1 architectures 810:822 complex architectures 802:822 not only terminal glycoepitopes but also complex architectures of glycans 761:833 Probing the array with several glycan-binding proteins uncovered that not only terminal glycoepitopes but also complex architectures of glycans can influence binding selectivity in unanticipated manners. 28630345 2 2 theme glycan-binding 353:366 arg1 proteins 368:375 glycan-binding proteins 353:375 glycan-binding proteins 353:375 This deficiency hampers investigations into the biology of glycan-binding proteins, which in turn complicates the biomedical use of this class of biomolecules. 28630345 1 3 theme asymmetrical 128:139 arg1 architectures 156:168 highly complex asymmetrical multiantennary architectures 113:168 highly complex asymmetrical multiantennary architectures 113:168 Despite mammalian glycans typically having highly complex asymmetrical multiantennary architectures, chemical and chemoenzymatic synthesis has almost exclusively focused on the preparation of simpler symmetrical structures. 28630345 5 4 link O-linked 902:909 arg1 glycans 911:917 O-linked glycans 902:917 O-linked glycans 902:917 N- and O-linked glycans express structural elements of HMOs, and thus, the reported synthetic principles will find broad applicability. 28630345 1 5 theme mammalian 78:86 arg1 glycans 88:94 mammalian glycans 78:94 mammalian glycans typically having highly complex asymmetrical multiantennary architectures 78:168 Despite mammalian glycans typically having highly complex asymmetrical multiantennary architectures, chemical and chemoenzymatic synthesis has almost exclusively focused on the preparation of simpler symmetrical structures. 28630345 3 6 theme glycosyltransferases 529:548 arg1 number 513:518 a limited number 503:518 a limited number of human glycosyltransferases 503:548 Herein, we describe an enzymatic strategy, using a limited number of human glycosyltransferases, to access a collection of 60 asymmetric, multiantennary human milk oligosaccharides (HMOs), which were used to develop a glycan microarray. 28630345 1 7 theme multiantennary 141:154 arg1 architectures 156:168 highly complex asymmetrical multiantennary architectures 113:168 highly complex asymmetrical multiantennary architectures 113:168 Despite mammalian glycans typically having highly complex asymmetrical multiantennary architectures, chemical and chemoenzymatic synthesis has almost exclusively focused on the preparation of simpler symmetrical structures. 28630345 5 8 theme O-linked 902:909 arg1 glycans 911:917 O-linked glycans 902:917 O-linked glycans 902:917 N- and O-linked glycans express structural elements of HMOs, and thus, the reported synthetic principles will find broad applicability. 28630345 3 9 theme enzymatic 477:485 arg1 strategy 487:494 an enzymatic strategy 474:494 an enzymatic strategy 474:494 Herein, we describe an enzymatic strategy, using a limited number of human glycosyltransferases, to access a collection of 60 asymmetric, multiantennary human milk oligosaccharides (HMOs), which were used to develop a glycan microarray. 28630345 5 10 theme structural 927:936 arg1 elements 938:945 structural elements 927:945 structural elements of HMOs 927:953 N- and O-linked glycans express structural elements of HMOs, and thus, the reported synthetic principles will find broad applicability. 28630345 3 11 theme asymmetric 580:589 arg1 HMOs 636:639 HMOs 636:639 HMOs 636:639 Herein, we describe an enzymatic strategy, using a limited number of human glycosyltransferases, to access a collection of 60 asymmetric, multiantennary human milk oligosaccharides (HMOs), which were used to develop a glycan microarray. 28630345 3 11 theme asymmetric 580:589 arg1 oligosaccharides 618:633 human milk oligosaccharides 607:633 60 asymmetric, multiantennary human milk oligosaccharides (HMOs) 577:640 Herein, we describe an enzymatic strategy, using a limited number of human glycosyltransferases, to access a collection of 60 asymmetric, multiantennary human milk oligosaccharides (HMOs), which were used to develop a glycan microarray. 28630345 3 12 theme oligosaccharides 618:633 arg1 collection 563:572 a collection 561:572 a collection 561:572 Herein, we describe an enzymatic strategy, using a limited number of human glycosyltransferases, to access a collection of 60 asymmetric, multiantennary human milk oligosaccharides (HMOs), which were used to develop a glycan microarray. 28630345 2 13 theme biomolecules 440:451 arg1 class 431:435 this class 426:435 this class of biomolecules 426:451 This deficiency hampers investigations into the biology of glycan-binding proteins, which in turn complicates the biomedical use of this class of biomolecules. 28630345 3 14 theme milk 613:616 arg1 HMOs 636:639 HMOs 636:639 HMOs 636:639 Herein, we describe an enzymatic strategy, using a limited number of human glycosyltransferases, to access a collection of 60 asymmetric, multiantennary human milk oligosaccharides (HMOs), which were used to develop a glycan microarray. 28630345 3 14 theme milk 613:616 arg1 oligosaccharides 618:633 human milk oligosaccharides 607:633 60 asymmetric, multiantennary human milk oligosaccharides (HMOs) 577:640 Herein, we describe an enzymatic strategy, using a limited number of human glycosyltransferases, to access a collection of 60 asymmetric, multiantennary human milk oligosaccharides (HMOs), which were used to develop a glycan microarray. 28630345 5 15 theme HMOs 950:953 arg1 elements 938:945 structural elements 927:945 structural elements of HMOs 927:953 N- and O-linked glycans express structural elements of HMOs, and thus, the reported synthetic principles will find broad applicability. 28630345 0 16 theme multiantennary 26:39 arg1 oligosaccharides 52:67 asymmetrical multiantennary human milk oligosaccharides 13:67 asymmetrical multiantennary human milk oligosaccharides 13:67 Synthesis of asymmetrical multiantennary human milk oligosaccharides. 28630345 1 17 theme complex 120:126 arg1 architectures 156:168 highly complex asymmetrical multiantennary architectures 113:168 highly complex asymmetrical multiantennary architectures 113:168 Despite mammalian glycans typically having highly complex asymmetrical multiantennary architectures, chemical and chemoenzymatic synthesis has almost exclusively focused on the preparation of simpler symmetrical structures. 28630345 0 18 theme asymmetrical 13:24 arg1 oligosaccharides 52:67 asymmetrical multiantennary human milk oligosaccharides 13:67 asymmetrical multiantennary human milk oligosaccharides 13:67 Synthesis of asymmetrical multiantennary human milk oligosaccharides. 28630345 5 19 theme synthetic 979:987 arg1 principles 989:998 the reported synthetic principles 966:998 the reported synthetic principles 966:998 N- and O-linked glycans express structural elements of HMOs, and thus, the reported synthetic principles will find broad applicability. 28630345 5 20 theme broad 1010:1014 arg1 applicability 1016:1028 broad applicability 1010:1028 broad applicability 1010:1028 N- and O-linked glycans express structural elements of HMOs, and thus, the reported synthetic principles will find broad applicability. 28630345 2 21 theme proteins 368:375 arg1 biology 342:348 the biology 338:348 the biology of glycan-binding proteins 338:375 This deficiency hampers investigations into the biology of glycan-binding proteins, which in turn complicates the biomedical use of this class of biomolecules. 28630345 2 22 theme class 431:435 arg1 use 419:421 the biomedical use 404:421 the biomedical use of this class of biomolecules 404:451 This deficiency hampers investigations into the biology of glycan-binding proteins, which in turn complicates the biomedical use of this class of biomolecules. 28630345 0 23 theme milk 47:50 arg1 oligosaccharides 52:67 asymmetrical multiantennary human milk oligosaccharides 13:67 asymmetrical multiantennary human milk oligosaccharides 13:67 Synthesis of asymmetrical multiantennary human milk oligosaccharides. 28630345 5 24 theme reported 970:977 arg1 principles 989:998 the reported synthetic principles 966:998 the reported synthetic principles 966:998 N- and O-linked glycans express structural elements of HMOs, and thus, the reported synthetic principles will find broad applicability. 28630345 4 25 with array 703:707 arg1 proteins 737:744 several glycan-binding proteins 714:744 several glycan-binding proteins uncovered that not only terminal glycoepitopes but also complex architectures of glycans can influence binding selectivity in unanticipated manners 714:892 Probing the array with several glycan-binding proteins uncovered that not only terminal glycoepitopes but also complex architectures of glycans can influence binding selectivity in unanticipated manners. 28630345 0 26 theme human 41:45 arg1 oligosaccharides 52:67 asymmetrical multiantennary human milk oligosaccharides 13:67 asymmetrical multiantennary human milk oligosaccharides 13:67 Synthesis of asymmetrical multiantennary human milk oligosaccharides. 28630345 4 27 theme unanticipated 872:884 arg1 manners 886:892 unanticipated manners 872:892 unanticipated manners 872:892 Probing the array with several glycan-binding proteins uncovered that not only terminal glycoepitopes but also complex architectures of glycans can influence binding selectivity in unanticipated manners. 28630345 1 28 theme simpler 262:268 arg1 structures 282:291 simpler symmetrical structures 262:291 simpler symmetrical structures 262:291 Despite mammalian glycans typically having highly complex asymmetrical multiantennary architectures, chemical and chemoenzymatic synthesis has almost exclusively focused on the preparation of simpler symmetrical structures. 28630345 3 29 theme glycan 672:677 arg1 microarray 679:688 a glycan microarray 670:688 a glycan microarray 670:688 Herein, we describe an enzymatic strategy, using a limited number of human glycosyltransferases, to access a collection of 60 asymmetric, multiantennary human milk oligosaccharides (HMOs), which were used to develop a glycan microarray. 28630345 2 30 theme biomedical 408:417 arg1 use 419:421 the biomedical use 404:421 the biomedical use of this class of biomolecules 404:451 This deficiency hampers investigations into the biology of glycan-binding proteins, which in turn complicates the biomedical use of this class of biomolecules. 28630345 0 31 theme oligosaccharides 52:67 arg1 Synthesis 0:8 Synthesis 0:8 Synthesis of asymmetrical multiantennary human milk oligosaccharides 0:67 Synthesis of asymmetrical multiantennary human milk oligosaccharides. 28630345 3 32 dep asymmetric 580:589 arg1 multiantennary 592:605 multiantennary 592:605 multiantennary 592:605 Herein, we describe an enzymatic strategy, using a limited number of human glycosyltransferases, to access a collection of 60 asymmetric, multiantennary human milk oligosaccharides (HMOs), which were used to develop a glycan microarray. 28630345 1 33 contain having 106:111 arg1 glycans 88:94 mammalian glycans 78:94 mammalian glycans typically having highly complex asymmetrical multiantennary architectures 78:168 Despite mammalian glycans typically having highly complex asymmetrical multiantennary architectures, chemical and chemoenzymatic synthesis has almost exclusively focused on the preparation of simpler symmetrical structures. 28630345 1 33 contain having 106:111 arg2 architectures 156:168 highly complex asymmetrical multiantennary architectures 113:168 highly complex asymmetrical multiantennary architectures 113:168 Despite mammalian glycans typically having highly complex asymmetrical multiantennary architectures, chemical and chemoenzymatic synthesis has almost exclusively focused on the preparation of simpler symmetrical structures. 28630345 4 34 theme binding 849:855 arg1 selectivity 857:867 binding selectivity 849:867 binding selectivity 849:867 Probing the array with several glycan-binding proteins uncovered that not only terminal glycoepitopes but also complex architectures of glycans can influence binding selectivity in unanticipated manners. 28630345 4 35 theme several 714:720 arg1 proteins 737:744 several glycan-binding proteins 714:744 several glycan-binding proteins uncovered that not only terminal glycoepitopes but also complex architectures of glycans can influence binding selectivity in unanticipated manners 714:892 Probing the array with several glycan-binding proteins uncovered that not only terminal glycoepitopes but also complex architectures of glycans can influence binding selectivity in unanticipated manners. 28630345 3 36 theme human 523:527 arg1 glycosyltransferases 529:548 human glycosyltransferases 523:548 human glycosyltransferases 523:548 Herein, we describe an enzymatic strategy, using a limited number of human glycosyltransferases, to access a collection of 60 asymmetric, multiantennary human milk oligosaccharides (HMOs), which were used to develop a glycan microarray. 28630345 3 37 theme human 607:611 arg1 HMOs 636:639 HMOs 636:639 HMOs 636:639 Herein, we describe an enzymatic strategy, using a limited number of human glycosyltransferases, to access a collection of 60 asymmetric, multiantennary human milk oligosaccharides (HMOs), which were used to develop a glycan microarray. 28630345 3 37 theme human 607:611 arg1 oligosaccharides 618:633 human milk oligosaccharides 607:633 60 asymmetric, multiantennary human milk oligosaccharides (HMOs) 577:640 Herein, we describe an enzymatic strategy, using a limited number of human glycosyltransferases, to access a collection of 60 asymmetric, multiantennary human milk oligosaccharides (HMOs), which were used to develop a glycan microarray. 28630345 1 38 theme symmetrical 270:280 arg1 structures 282:291 simpler symmetrical structures 262:291 simpler symmetrical structures 262:291 Despite mammalian glycans typically having highly complex asymmetrical multiantennary architectures, chemical and chemoenzymatic synthesis has almost exclusively focused on the preparation of simpler symmetrical structures. 28630345 4 39 theme glycans 827:833 arg1 glycoepitopes 779:791 terminal glycoepitopes 770:791 not only terminal glycoepitopes but also complex architectures of glycans 761:833 Probing the array with several glycan-binding proteins uncovered that not only terminal glycoepitopes but also complex architectures of glycans can influence binding selectivity in unanticipated manners. 28630345 4 39 theme glycans 827:833 arg1 architectures 810:822 complex architectures 802:822 not only terminal glycoepitopes but also complex architectures of glycans 761:833 Probing the array with several glycan-binding proteins uncovered that not only terminal glycoepitopes but also complex architectures of glycans can influence binding selectivity in unanticipated manners. 28630345 4 40 theme terminal 770:777 arg1 glycoepitopes 779:791 terminal glycoepitopes 770:791 not only terminal glycoepitopes but also complex architectures of glycans 761:833 Probing the array with several glycan-binding proteins uncovered that not only terminal glycoepitopes but also complex architectures of glycans can influence binding selectivity in unanticipated manners. 28630345 1 41 theme chemical 171:178 arg1 synthesis 199:207 chemical and chemoenzymatic synthesis 171:207 chemical and chemoenzymatic synthesis 171:207 Despite mammalian glycans typically having highly complex asymmetrical multiantennary architectures, chemical and chemoenzymatic synthesis has almost exclusively focused on the preparation of simpler symmetrical structures. 28630345 1 42 theme structures 282:291 arg1 preparation 247:257 the preparation 243:257 the preparation of simpler symmetrical structures 243:291 Despite mammalian glycans typically having highly complex asymmetrical multiantennary architectures, chemical and chemoenzymatic synthesis has almost exclusively focused on the preparation of simpler symmetrical structures. 28630345 3 43 theme limited 505:511 arg1 number 513:518 a limited number 503:518 a limited number of human glycosyltransferases 503:548 Herein, we describe an enzymatic strategy, using a limited number of human glycosyltransferases, to access a collection of 60 asymmetric, multiantennary human milk oligosaccharides (HMOs), which were used to develop a glycan microarray. 28630345 3 44 used used 654:657 arg2 collection 563:572 a collection 561:572 a collection 561:572 Herein, we describe an enzymatic strategy, using a limited number of human glycosyltransferases, to access a collection of 60 asymmetric, multiantennary human milk oligosaccharides (HMOs), which were used to develop a glycan microarray. 28630345 1 45 theme chemoenzymatic 184:197 arg1 synthesis 199:207 chemical and chemoenzymatic synthesis 171:207 chemical and chemoenzymatic synthesis 171:207 Despite mammalian glycans typically having highly complex asymmetrical multiantennary architectures, chemical and chemoenzymatic synthesis has almost exclusively focused on the preparation of simpler symmetrical structures. 28389114 3 0 theme short 327:331 arg1 synthesis 347:355 A short and efficient synthesis 325:355 A short and efficient synthesis 325:355 A short and efficient synthesis was developed based on an epoxide ring-opening reaction by a mannosyl thiolate, generated in situ from the corresponding thioacetate. 28389114 1 1 dep synthesis 89:97 arg1 The 85:87 The 85:87 The 85:87 The synthesis and conformational analysis of pseudo-thio-1,2-dimannoside are described. 28389114 4 2 theme pseudo-1,2-dimannoside 626:647 arg1 behavior 610:617 the conformational behavior 591:617 the conformational behavior of the pseudo-1,2-dimannoside 591:647 NMR-NOESY studies supported by MM3∗ calculations showed that the pseudo-thio-1,2-dimannoside shares the conformational behavior of the pseudo-1,2-dimannoside and is a structural mimic of the natural disaccharide. 28389114 4 3 theme NMR-NOESY 491:499 arg1 studies 501:507 NMR-NOESY studies 491:507 NMR-NOESY studies supported by MM3∗ calculations 491:538 NMR-NOESY studies supported by MM3∗ calculations showed that the pseudo-thio-1,2-dimannoside shares the conformational behavior of the pseudo-1,2-dimannoside and is a structural mimic of the natural disaccharide. 28389114 2 4 theme increased 280:288 arg1 stability 290:298 increased stability 280:298 increased stability to enzymatic hydrolysis 280:322 This molecule mimics mannobioside (Manα(1,2)Man) and is an analog of pseudo-1,2-dimannoside, with expected increased stability to enzymatic hydrolysis. 28389114 2 5 dep pseudo-1,2-dimannoside 242:263 arg1 expected 271:278 expected 271:278 expected increased stability to enzymatic hydrolysis 271:322 This molecule mimics mannobioside (Manα(1,2)Man) and is an analog of pseudo-1,2-dimannoside, with expected increased stability to enzymatic hydrolysis. 28389114 5 6 theme corresponding 783:795 arg1 analog 806:811 the corresponding O-linked analog 779:811 the corresponding O-linked analog 779:811 Its affinity for DC-SIGN was measured by SPR and found to be comparable to the corresponding O-linked analog, offering good opportunities for further developments. 28389114 5 7 theme good 823:826 arg1 opportunities 828:840 good opportunities 823:840 good opportunities for further developments 823:865 Its affinity for DC-SIGN was measured by SPR and found to be comparable to the corresponding O-linked analog, offering good opportunities for further developments. 28389114 3 8 theme ring-opening 391:402 arg1 reaction 404:411 an epoxide ring-opening reaction 380:411 an epoxide ring-opening reaction 380:411 A short and efficient synthesis was developed based on an epoxide ring-opening reaction by a mannosyl thiolate, generated in situ from the corresponding thioacetate. 28389114 5 9 theme O-linked 797:804 arg1 analog 806:811 the corresponding O-linked analog 779:811 the corresponding O-linked analog 779:811 Its affinity for DC-SIGN was measured by SPR and found to be comparable to the corresponding O-linked analog, offering good opportunities for further developments. 28389114 0 10 theme Facile 0:5 arg1 access 7:12 Facile access 0:12 Facile access to pseudo-thio-1,2-dimannoside 0:43 Facile access to pseudo-thio-1,2-dimannoside, a new glycomimetic DC-SIGN antagonist. 28389114 0 10 theme Facile 0:5 arg1 antagonist 73:82 a new glycomimetic DC-SIGN antagonist 46:82 a new glycomimetic DC-SIGN antagonist 46:82 Facile access to pseudo-thio-1,2-dimannoside, a new glycomimetic DC-SIGN antagonist. 28389114 4 11 theme conformational 595:608 arg1 behavior 610:617 the conformational behavior 591:617 the conformational behavior of the pseudo-1,2-dimannoside 591:647 NMR-NOESY studies supported by MM3∗ calculations showed that the pseudo-thio-1,2-dimannoside shares the conformational behavior of the pseudo-1,2-dimannoside and is a structural mimic of the natural disaccharide. 28389114 1 12 theme conformational 103:116 arg1 analysis 118:125 conformational analysis 103:125 conformational analysis 103:125 The synthesis and conformational analysis of pseudo-thio-1,2-dimannoside are described. 28389114 3 13 theme corresponding 464:476 arg1 thioacetate 478:488 the corresponding thioacetate 460:488 the corresponding thioacetate 460:488 A short and efficient synthesis was developed based on an epoxide ring-opening reaction by a mannosyl thiolate, generated in situ from the corresponding thioacetate. 28389114 3 14 theme epoxide 383:389 arg1 reaction 404:411 an epoxide ring-opening reaction 380:411 an epoxide ring-opening reaction 380:411 A short and efficient synthesis was developed based on an epoxide ring-opening reaction by a mannosyl thiolate, generated in situ from the corresponding thioacetate. 28389114 2 15 theme enzymatic 303:311 arg1 hydrolysis 313:322 enzymatic hydrolysis 303:322 enzymatic hydrolysis 303:322 This molecule mimics mannobioside (Manα(1,2)Man) and is an analog of pseudo-1,2-dimannoside, with expected increased stability to enzymatic hydrolysis. 28389114 3 16 theme mannosyl 418:425 arg1 thiolate 427:434 a mannosyl thiolate 416:434 a mannosyl thiolate 416:434 A short and efficient synthesis was developed based on an epoxide ring-opening reaction by a mannosyl thiolate, generated in situ from the corresponding thioacetate. 28389114 2 17 theme Manα 208:211 arg1 mannobioside 194:205 mannobioside 194:205 mannobioside (Manα(1,2)Man) 194:220 This molecule mimics mannobioside (Manα(1,2)Man) and is an analog of pseudo-1,2-dimannoside, with expected increased stability to enzymatic hydrolysis. 28389114 2 17 theme Manα 208:211 arg1 Man 217:219 Manα(1,2)Man 208:219 Manα(1,2)Man 208:219 This molecule mimics mannobioside (Manα(1,2)Man) and is an analog of pseudo-1,2-dimannoside, with expected increased stability to enzymatic hydrolysis. 28389114 0 18 theme glycomimetic 52:63 arg1 antagonist 73:82 a new glycomimetic DC-SIGN antagonist 46:82 a new glycomimetic DC-SIGN antagonist 46:82 Facile access to pseudo-thio-1,2-dimannoside, a new glycomimetic DC-SIGN antagonist. 28389114 0 18 theme glycomimetic 52:63 arg1 access 7:12 Facile access 0:12 Facile access to pseudo-thio-1,2-dimannoside 0:43 Facile access to pseudo-thio-1,2-dimannoside, a new glycomimetic DC-SIGN antagonist. 28389114 5 19 theme further 846:852 arg1 developments 854:865 further developments 846:865 further developments 846:865 Its affinity for DC-SIGN was measured by SPR and found to be comparable to the corresponding O-linked analog, offering good opportunities for further developments. 28389114 0 20 theme new 48:50 arg1 antagonist 73:82 a new glycomimetic DC-SIGN antagonist 46:82 a new glycomimetic DC-SIGN antagonist 46:82 Facile access to pseudo-thio-1,2-dimannoside, a new glycomimetic DC-SIGN antagonist. 28389114 0 20 theme new 48:50 arg1 access 7:12 Facile access 0:12 Facile access to pseudo-thio-1,2-dimannoside 0:43 Facile access to pseudo-thio-1,2-dimannoside, a new glycomimetic DC-SIGN antagonist. 28389114 1 21 theme pseudo-thio-1,2-dimannoside 130:156 arg1 synthesis 89:97 synthesis 89:97 synthesis 89:97 The synthesis and conformational analysis of pseudo-thio-1,2-dimannoside are described. 28389114 1 21 theme pseudo-thio-1,2-dimannoside 130:156 arg1 analysis 118:125 conformational analysis 103:125 conformational analysis 103:125 The synthesis and conformational analysis of pseudo-thio-1,2-dimannoside are described. 28389114 5 22 link O-linked 797:804 arg1 analog 806:811 the corresponding O-linked analog 779:811 the corresponding O-linked analog 779:811 Its affinity for DC-SIGN was measured by SPR and found to be comparable to the corresponding O-linked analog, offering good opportunities for further developments. 28389114 3 23 theme efficient 337:345 arg1 synthesis 347:355 A short and efficient synthesis 325:355 A short and efficient synthesis 325:355 A short and efficient synthesis was developed based on an epoxide ring-opening reaction by a mannosyl thiolate, generated in situ from the corresponding thioacetate. 28389114 2 24 theme 1,2 213:215 arg1 mannobioside 194:205 mannobioside 194:205 mannobioside (Manα(1,2)Man) 194:220 This molecule mimics mannobioside (Manα(1,2)Man) and is an analog of pseudo-1,2-dimannoside, with expected increased stability to enzymatic hydrolysis. 28389114 2 24 theme 1,2 213:215 arg1 Man 217:219 Manα(1,2)Man 208:219 Manα(1,2)Man 208:219 This molecule mimics mannobioside (Manα(1,2)Man) and is an analog of pseudo-1,2-dimannoside, with expected increased stability to enzymatic hydrolysis. 28389114 2 25 theme pseudo-1,2-dimannoside 242:263 arg1 analog 232:237 an analog 229:237 an analog of pseudo-1,2-dimannoside, with expected increased stability to enzymatic hydrolysis 229:322 This molecule mimics mannobioside (Manα(1,2)Man) and is an analog of pseudo-1,2-dimannoside, with expected increased stability to enzymatic hydrolysis. 28389114 4 26 theme natural 682:688 arg1 disaccharide 690:701 the natural disaccharide 678:701 the natural disaccharide 678:701 NMR-NOESY studies supported by MM3∗ calculations showed that the pseudo-thio-1,2-dimannoside shares the conformational behavior of the pseudo-1,2-dimannoside and is a structural mimic of the natural disaccharide. 28389114 0 27 theme DC-SIGN 65:71 arg1 antagonist 73:82 a new glycomimetic DC-SIGN antagonist 46:82 a new glycomimetic DC-SIGN antagonist 46:82 Facile access to pseudo-thio-1,2-dimannoside, a new glycomimetic DC-SIGN antagonist. 28389114 0 27 theme DC-SIGN 65:71 arg1 access 7:12 Facile access 0:12 Facile access to pseudo-thio-1,2-dimannoside 0:43 Facile access to pseudo-thio-1,2-dimannoside, a new glycomimetic DC-SIGN antagonist. 28389114 4 28 theme MM3∗ 522:525 arg1 calculations 527:538 MM3∗ calculations 522:538 MM3∗ calculations 522:538 NMR-NOESY studies supported by MM3∗ calculations showed that the pseudo-thio-1,2-dimannoside shares the conformational behavior of the pseudo-1,2-dimannoside and is a structural mimic of the natural disaccharide. 28346405 1 0 theme nucleocytoplasmic 148:164 arg1 proteins 166:173 nucleocytoplasmic proteins 148:173 nucleocytoplasmic proteins 148:173 O-GlcNAc hydrolase (OGA) removes O-linked N-acetylglucosamine (O-GlcNAc) from a myriad of nucleocytoplasmic proteins. 28346405 1 1 theme O-GlcNAc 58:65 arg1 OGA 78:80 OGA 78:80 OGA 78:80 O-GlcNAc hydrolase (OGA) removes O-linked N-acetylglucosamine (O-GlcNAc) from a myriad of nucleocytoplasmic proteins. 28346405 1 1 theme O-GlcNAc 58:65 arg1 hydrolase 67:75 O-GlcNAc hydrolase 58:75 O-GlcNAc hydrolase (OGA) 58:81 O-GlcNAc hydrolase (OGA) removes O-linked N-acetylglucosamine (O-GlcNAc) from a myriad of nucleocytoplasmic proteins. 28346405 3 2 theme inhibitors 546:555 arg1 design 536:541 the design 532:541 the design of inhibitors that have clinical value 532:580 Structures of OGA in complex with a series of inhibitors define a precise blueprint for the design of inhibitors that have clinical value. 28346405 3 3 theme inhibitors 490:499 arg1 series 480:485 a series 478:485 a series of inhibitors 478:499 Structures of OGA in complex with a series of inhibitors define a precise blueprint for the design of inhibitors that have clinical value. 28346405 2 4 theme OGA 284:286 arg1 structure 265:273 the three-dimensional structure 243:273 the three-dimensional structure of human OGA 243:286 Through co-expression and assembly of OGA fragments, we determined the three-dimensional structure of human OGA, revealing an unusual helix-exchanged dimer that lays a structural foundation for an improved understanding of substrate recognition and regulation of OGA. 28346405 1 5 theme proteins 166:173 arg1 myriad 138:143 a myriad 136:143 a myriad of nucleocytoplasmic proteins 136:173 O-GlcNAc hydrolase (OGA) removes O-linked N-acetylglucosamine (O-GlcNAc) from a myriad of nucleocytoplasmic proteins. 28346405 2 6 theme human 278:282 arg1 OGA 284:286 human OGA 278:286 human OGA 278:286 Through co-expression and assembly of OGA fragments, we determined the three-dimensional structure of human OGA, revealing an unusual helix-exchanged dimer that lays a structural foundation for an improved understanding of substrate recognition and regulation of OGA. 28346405 2 7 theme substrate 399:407 arg1 recognition 409:419 substrate recognition 399:419 substrate recognition 399:419 Through co-expression and assembly of OGA fragments, we determined the three-dimensional structure of human OGA, revealing an unusual helix-exchanged dimer that lays a structural foundation for an improved understanding of substrate recognition and regulation of OGA. 28346405 3 8 theme clinical 567:574 arg1 value 576:580 clinical value 567:580 clinical value 567:580 Structures of OGA in complex with a series of inhibitors define a precise blueprint for the design of inhibitors that have clinical value. 28346405 0 9 theme Structural 0:9 arg1 insight 26:32 Structural and functional insight 0:32 Structural and functional insight into human O-GlcNAcase 0:55 Structural and functional insight into human O-GlcNAcase. 28346405 3 10 contain have 562:565 arg2 value 576:580 clinical value 567:580 clinical value 567:580 Structures of OGA in complex with a series of inhibitors define a precise blueprint for the design of inhibitors that have clinical value. 28346405 3 10 contain have 562:565 arg1 inhibitors 546:555 inhibitors 546:555 inhibitors that have clinical value 546:580 Structures of OGA in complex with a series of inhibitors define a precise blueprint for the design of inhibitors that have clinical value. 28346405 2 11 theme helix-exchanged 310:324 arg1 dimer 326:330 an unusual helix-exchanged dimer 299:330 an unusual helix-exchanged dimer that lays a structural foundation for an improved understanding of substrate recognition and regulation of OGA 299:441 Through co-expression and assembly of OGA fragments, we determined the three-dimensional structure of human OGA, revealing an unusual helix-exchanged dimer that lays a structural foundation for an improved understanding of substrate recognition and regulation of OGA. 28346405 2 12 theme unusual 302:308 arg1 dimer 326:330 an unusual helix-exchanged dimer 299:330 an unusual helix-exchanged dimer that lays a structural foundation for an improved understanding of substrate recognition and regulation of OGA 299:441 Through co-expression and assembly of OGA fragments, we determined the three-dimensional structure of human OGA, revealing an unusual helix-exchanged dimer that lays a structural foundation for an improved understanding of substrate recognition and regulation of OGA. 28346405 2 13 theme OGA 439:441 arg1 regulation 425:434 regulation 425:434 regulation of OGA 425:441 Through co-expression and assembly of OGA fragments, we determined the three-dimensional structure of human OGA, revealing an unusual helix-exchanged dimer that lays a structural foundation for an improved understanding of substrate recognition and regulation of OGA. 28346405 2 13 theme OGA 439:441 arg1 recognition 409:419 substrate recognition 399:419 substrate recognition 399:419 Through co-expression and assembly of OGA fragments, we determined the three-dimensional structure of human OGA, revealing an unusual helix-exchanged dimer that lays a structural foundation for an improved understanding of substrate recognition and regulation of OGA. 28346405 0 14 theme functional 15:24 arg1 insight 26:32 Structural and functional insight 0:32 Structural and functional insight into human O-GlcNAcase 0:55 Structural and functional insight into human O-GlcNAcase. 28346405 3 15 with complex 465:471 arg1 series 480:485 a series 478:485 a series of inhibitors 478:499 Structures of OGA in complex with a series of inhibitors define a precise blueprint for the design of inhibitors that have clinical value. 28346405 3 16 theme precise 510:516 arg1 blueprint 518:526 a precise blueprint 508:526 a precise blueprint for the design of inhibitors that have clinical value 508:580 Structures of OGA in complex with a series of inhibitors define a precise blueprint for the design of inhibitors that have clinical value. 28346405 0 17 theme human 39:43 arg1 O-GlcNAcase 45:55 human O-GlcNAcase 39:55 human O-GlcNAcase 39:55 Structural and functional insight into human O-GlcNAcase. 28346405 2 18 theme regulation 425:434 arg1 understanding 382:394 an improved understanding 370:394 an improved understanding of substrate recognition and regulation of OGA 370:441 Through co-expression and assembly of OGA fragments, we determined the three-dimensional structure of human OGA, revealing an unusual helix-exchanged dimer that lays a structural foundation for an improved understanding of substrate recognition and regulation of OGA. 28346405 2 19 theme recognition 409:419 arg1 understanding 382:394 an improved understanding 370:394 an improved understanding of substrate recognition and regulation of OGA 370:441 Through co-expression and assembly of OGA fragments, we determined the three-dimensional structure of human OGA, revealing an unusual helix-exchanged dimer that lays a structural foundation for an improved understanding of substrate recognition and regulation of OGA. 28346405 2 20 theme structural 344:353 arg1 foundation 355:364 a structural foundation 342:364 a structural foundation for an improved understanding of substrate recognition and regulation of OGA 342:441 Through co-expression and assembly of OGA fragments, we determined the three-dimensional structure of human OGA, revealing an unusual helix-exchanged dimer that lays a structural foundation for an improved understanding of substrate recognition and regulation of OGA. 28346405 2 21 theme OGA 214:216 arg1 fragments 218:226 OGA fragments 214:226 OGA fragments 214:226 Through co-expression and assembly of OGA fragments, we determined the three-dimensional structure of human OGA, revealing an unusual helix-exchanged dimer that lays a structural foundation for an improved understanding of substrate recognition and regulation of OGA. 28346405 2 22 theme fragments 218:226 arg1 assembly 202:209 assembly 202:209 assembly 202:209 Through co-expression and assembly of OGA fragments, we determined the three-dimensional structure of human OGA, revealing an unusual helix-exchanged dimer that lays a structural foundation for an improved understanding of substrate recognition and regulation of OGA. 28346405 2 22 theme fragments 218:226 arg1 co-expression 184:196 co-expression 184:196 co-expression 184:196 Through co-expression and assembly of OGA fragments, we determined the three-dimensional structure of human OGA, revealing an unusual helix-exchanged dimer that lays a structural foundation for an improved understanding of substrate recognition and regulation of OGA. 28346405 1 23 theme O-linked 91:98 arg1 O-GlcNAc 121:128 O-GlcNAc 121:128 O-GlcNAc 121:128 O-GlcNAc hydrolase (OGA) removes O-linked N-acetylglucosamine (O-GlcNAc) from a myriad of nucleocytoplasmic proteins. 28346405 1 23 theme O-linked 91:98 arg1 N-acetylglucosamine 100:118 O-linked N-acetylglucosamine 91:118 O-linked N-acetylglucosamine (O-GlcNAc) 91:129 O-GlcNAc hydrolase (OGA) removes O-linked N-acetylglucosamine (O-GlcNAc) from a myriad of nucleocytoplasmic proteins. 28346405 1 24 link O-linked 91:98 arg1 O-GlcNAc 121:128 O-GlcNAc 121:128 O-GlcNAc 121:128 O-GlcNAc hydrolase (OGA) removes O-linked N-acetylglucosamine (O-GlcNAc) from a myriad of nucleocytoplasmic proteins. 28346405 1 24 link O-linked 91:98 arg1 N-acetylglucosamine 100:118 O-linked N-acetylglucosamine 91:118 O-linked N-acetylglucosamine (O-GlcNAc) 91:129 O-GlcNAc hydrolase (OGA) removes O-linked N-acetylglucosamine (O-GlcNAc) from a myriad of nucleocytoplasmic proteins. 28346405 2 25 theme three-dimensional 247:263 arg1 structure 265:273 the three-dimensional structure 243:273 the three-dimensional structure of human OGA 243:286 Through co-expression and assembly of OGA fragments, we determined the three-dimensional structure of human OGA, revealing an unusual helix-exchanged dimer that lays a structural foundation for an improved understanding of substrate recognition and regulation of OGA. 28346405 3 26 from Structures 444:453 arg1 complex 465:471 complex 465:471 complex with a series of inhibitors 465:499 Structures of OGA in complex with a series of inhibitors define a precise blueprint for the design of inhibitors that have clinical value. 28346405 2 27 theme improved 373:380 arg1 understanding 382:394 an improved understanding 370:394 an improved understanding of substrate recognition and regulation of OGA 370:441 Through co-expression and assembly of OGA fragments, we determined the three-dimensional structure of human OGA, revealing an unusual helix-exchanged dimer that lays a structural foundation for an improved understanding of substrate recognition and regulation of OGA. 28346405 3 28 theme OGA 458:460 arg1 Structures 444:453 Structures 444:453 Structures of OGA in complex with a series of inhibitors 444:499 Structures of OGA in complex with a series of inhibitors define a precise blueprint for the design of inhibitors that have clinical value. 27975253 1 0 theme pathologies 290:300 arg1 half 265:268 one half 261:268 one half of the two hallmark pathologies of Alzheimer's disease (AD) 261:328 Assembly of the microtubule-associated protein tau (tau) into paired helical filaments that ultimately give rise to neurofibrillary tangles (NFTs) makes up one half of the two hallmark pathologies of Alzheimer's disease (AD). 27975253 1 1 theme protein 144:150 arg1 tau 157:159 the microtubule-associated protein tau (tau) 117:160 the microtubule-associated protein tau (tau) 117:160 Assembly of the microtubule-associated protein tau (tau) into paired helical filaments that ultimately give rise to neurofibrillary tangles (NFTs) makes up one half of the two hallmark pathologies of Alzheimer's disease (AD). 27975253 2 2 with proteins 500:507 arg1 moieties 546:553 N-acetyl-D-glucosamine (GlcNAc) moieties 514:553 N-acetyl-D-glucosamine (GlcNAc) moieties 514:553 Tau has been shown to be modified with O-linked N-acetylglucosamine residues (O-GlcNAc), which is the modification of serine and threonine residues of nucleocytoplasmic proteins with N-acetyl-D-glucosamine (GlcNAc) moieties. 27975253 1 3 theme neurofibrillary 221:235 arg1 tangles 237:243 neurofibrillary tangles 221:243 neurofibrillary tangles (NFTs) 221:250 Assembly of the microtubule-associated protein tau (tau) into paired helical filaments that ultimately give rise to neurofibrillary tangles (NFTs) makes up one half of the two hallmark pathologies of Alzheimer's disease (AD). 27975253 1 3 theme neurofibrillary 221:235 arg1 NFTs 246:249 NFTs 246:249 NFTs 246:249 Assembly of the microtubule-associated protein tau (tau) into paired helical filaments that ultimately give rise to neurofibrillary tangles (NFTs) makes up one half of the two hallmark pathologies of Alzheimer's disease (AD). 27975253 3 4 theme symptoms 649:656 arg1 progression 634:644 the progression 630:644 the progression of symptoms in these mice 630:670 Increasing O-GlcNAc in mouse models of tauopathy has been shown to hinder the progression of symptoms in these mice and impair the aggregation of tau into NFTs. 27975253 4 5 theme protective 777:786 arg1 effects 788:794 the protective effects 773:794 the protective effects observed in tauopathy mouse models 773:829 In order to study how O-GlcNAc on tau may contribute to the protective effects observed in tauopathy mouse models, it is beneficial to study O-GlcNAc modified tau in vitro. 27975253 1 6 theme tau 152:154 arg1 tau 157:159 the microtubule-associated protein tau (tau) 117:160 the microtubule-associated protein tau (tau) 117:160 Assembly of the microtubule-associated protein tau (tau) into paired helical filaments that ultimately give rise to neurofibrillary tangles (NFTs) makes up one half of the two hallmark pathologies of Alzheimer's disease (AD). 27975253 0 7 theme O-GlcNAc 83:90 arg1 Tau 92:94 Ser400 O-GlcNAc Tau 76:94 Ser400 O-GlcNAc Tau 76:94 Production of O-GlcNAc Modified Recombinant Tau in E. coli and Detection of Ser400 O-GlcNAc Tau In Vivo. 27975253 0 8 from Production 0:9 arg1 coli 54:57 E. coli 51:57 E. coli 51:57 Production of O-GlcNAc Modified Recombinant Tau in E. coli and Detection of Ser400 O-GlcNAc Tau In Vivo. 27975253 0 9 theme Ser400 76:81 arg1 Tau 92:94 Ser400 O-GlcNAc Tau 76:94 Ser400 O-GlcNAc Tau 76:94 Production of O-GlcNAc Modified Recombinant Tau in E. coli and Detection of Ser400 O-GlcNAc Tau In Vivo. 27975253 1 10 theme disease 317:323 arg1 pathologies 290:300 the two hallmark pathologies 273:300 the two hallmark pathologies of Alzheimer's disease (AD) 273:328 Assembly of the microtubule-associated protein tau (tau) into paired helical filaments that ultimately give rise to neurofibrillary tangles (NFTs) makes up one half of the two hallmark pathologies of Alzheimer's disease (AD). 27975253 2 11 link O-linked 370:377 arg1 O-GlcNAc 409:416 O-GlcNAc 409:416 O-GlcNAc 409:416 Tau has been shown to be modified with O-linked N-acetylglucosamine residues (O-GlcNAc), which is the modification of serine and threonine residues of nucleocytoplasmic proteins with N-acetyl-D-glucosamine (GlcNAc) moieties. 27975253 2 11 link O-linked 370:377 arg1 modification 433:444 the modification 429:444 the modification of serine and threonine residues of nucleocytoplasmic proteins with N-acetyl-D-glucosamine (GlcNAc) moieties 429:553 Tau has been shown to be modified with O-linked N-acetylglucosamine residues (O-GlcNAc), which is the modification of serine and threonine residues of nucleocytoplasmic proteins with N-acetyl-D-glucosamine (GlcNAc) moieties. 27975253 2 11 link O-linked 370:377 arg1 residues 399:406 O-linked N-acetylglucosamine residues 370:406 O-linked N-acetylglucosamine residues (O-GlcNAc) 370:417 Tau has been shown to be modified with O-linked N-acetylglucosamine residues (O-GlcNAc), which is the modification of serine and threonine residues of nucleocytoplasmic proteins with N-acetyl-D-glucosamine (GlcNAc) moieties. 27975253 3 12 from O-GlcNAc 567:574 arg1 models 585:590 mouse models 579:590 mouse models of tauopathy 579:603 Increasing O-GlcNAc in mouse models of tauopathy has been shown to hinder the progression of symptoms in these mice and impair the aggregation of tau into NFTs. 27975253 0 13 theme Tau 92:94 arg1 Detection 63:71 Detection 63:71 Detection of Ser400 O-GlcNAc Tau In Vivo 63:102 Production of O-GlcNAc Modified Recombinant Tau in E. coli and Detection of Ser400 O-GlcNAc Tau In Vivo. 27975253 0 13 theme Tau 92:94 arg1 Production 0:9 Production 0:9 Production of O-GlcNAc Modified Recombinant Tau in E. coli 0:57 Production of O-GlcNAc Modified Recombinant Tau in E. coli and Detection of Ser400 O-GlcNAc Tau In Vivo. 27975253 7 14 from lysates 1171:1177 arg1 tau 1156:1158 tau 1156:1158 tau from brain lysates 1156:1177 We further describe the detection of Ser400 O-GlcNAc on tau from brain lysates. 27975253 1 15 theme tau 157:159 arg1 Assembly 105:112 Assembly 105:112 Assembly of the microtubule-associated protein tau (tau) into paired helical filaments that ultimately give rise to neurofibrillary tangles (NFTs) 105:250 Assembly of the microtubule-associated protein tau (tau) into paired helical filaments that ultimately give rise to neurofibrillary tangles (NFTs) makes up one half of the two hallmark pathologies of Alzheimer's disease (AD). 27975253 2 16 theme N-acetylglucosamine 379:397 arg1 O-GlcNAc 409:416 O-GlcNAc 409:416 O-GlcNAc 409:416 Tau has been shown to be modified with O-linked N-acetylglucosamine residues (O-GlcNAc), which is the modification of serine and threonine residues of nucleocytoplasmic proteins with N-acetyl-D-glucosamine (GlcNAc) moieties. 27975253 2 16 theme N-acetylglucosamine 379:397 arg1 modification 433:444 the modification 429:444 the modification of serine and threonine residues of nucleocytoplasmic proteins with N-acetyl-D-glucosamine (GlcNAc) moieties 429:553 Tau has been shown to be modified with O-linked N-acetylglucosamine residues (O-GlcNAc), which is the modification of serine and threonine residues of nucleocytoplasmic proteins with N-acetyl-D-glucosamine (GlcNAc) moieties. 27975253 2 16 theme N-acetylglucosamine 379:397 arg1 residues 399:406 O-linked N-acetylglucosamine residues 370:406 O-linked N-acetylglucosamine residues (O-GlcNAc) 370:417 Tau has been shown to be modified with O-linked N-acetylglucosamine residues (O-GlcNAc), which is the modification of serine and threonine residues of nucleocytoplasmic proteins with N-acetyl-D-glucosamine (GlcNAc) moieties. 27975253 4 17 theme tauopathy 808:816 arg1 models 824:829 tauopathy mouse models 808:829 tauopathy mouse models 808:829 In order to study how O-GlcNAc on tau may contribute to the protective effects observed in tauopathy mouse models, it is beneficial to study O-GlcNAc modified tau in vitro. 27975253 2 18 theme O-linked 370:377 arg1 O-GlcNAc 409:416 O-GlcNAc 409:416 O-GlcNAc 409:416 Tau has been shown to be modified with O-linked N-acetylglucosamine residues (O-GlcNAc), which is the modification of serine and threonine residues of nucleocytoplasmic proteins with N-acetyl-D-glucosamine (GlcNAc) moieties. 27975253 2 18 theme O-linked 370:377 arg1 modification 433:444 the modification 429:444 the modification of serine and threonine residues of nucleocytoplasmic proteins with N-acetyl-D-glucosamine (GlcNAc) moieties 429:553 Tau has been shown to be modified with O-linked N-acetylglucosamine residues (O-GlcNAc), which is the modification of serine and threonine residues of nucleocytoplasmic proteins with N-acetyl-D-glucosamine (GlcNAc) moieties. 27975253 2 18 theme O-linked 370:377 arg1 residues 399:406 O-linked N-acetylglucosamine residues 370:406 O-linked N-acetylglucosamine residues (O-GlcNAc) 370:417 Tau has been shown to be modified with O-linked N-acetylglucosamine residues (O-GlcNAc), which is the modification of serine and threonine residues of nucleocytoplasmic proteins with N-acetyl-D-glucosamine (GlcNAc) moieties. 27975253 2 19 mod modified 356:363 arg1 Tau 331:333 Tau 331:333 Tau 331:333 Tau has been shown to be modified with O-linked N-acetylglucosamine residues (O-GlcNAc), which is the modification of serine and threonine residues of nucleocytoplasmic proteins with N-acetyl-D-glucosamine (GlcNAc) moieties. 27975253 2 19 mod modified 356:363 arg3 modification 433:444 the modification 429:444 the modification of serine and threonine residues of nucleocytoplasmic proteins with N-acetyl-D-glucosamine (GlcNAc) moieties 429:553 Tau has been shown to be modified with O-linked N-acetylglucosamine residues (O-GlcNAc), which is the modification of serine and threonine residues of nucleocytoplasmic proteins with N-acetyl-D-glucosamine (GlcNAc) moieties. 27975253 2 19 mod modified 356:363 arg3 residues 399:406 O-linked N-acetylglucosamine residues 370:406 O-linked N-acetylglucosamine residues (O-GlcNAc) 370:417 Tau has been shown to be modified with O-linked N-acetylglucosamine residues (O-GlcNAc), which is the modification of serine and threonine residues of nucleocytoplasmic proteins with N-acetyl-D-glucosamine (GlcNAc) moieties. 27975253 2 19 mod modified 356:363 arg3 O-GlcNAc 409:416 O-GlcNAc 409:416 O-GlcNAc 409:416 Tau has been shown to be modified with O-linked N-acetylglucosamine residues (O-GlcNAc), which is the modification of serine and threonine residues of nucleocytoplasmic proteins with N-acetyl-D-glucosamine (GlcNAc) moieties. 27975253 6 20 theme sites 1069:1073 arg1 identification 1029:1042 the identification 1025:1042 the identification of O-GlcNAc modification sites on tau including Ser400 1025:1097 These methods have enabled the identification of O-GlcNAc modification sites on tau including Ser400. 27975253 0 21 theme Modified 23:30 arg1 Tau 44:46 O-GlcNAc Modified Recombinant Tau 14:46 O-GlcNAc Modified Recombinant Tau 14:46 Production of O-GlcNAc Modified Recombinant Tau in E. coli and Detection of Ser400 O-GlcNAc Tau In Vivo. 27975253 2 22 theme nucleocytoplasmic 482:498 arg1 proteins 500:507 nucleocytoplasmic proteins 482:507 nucleocytoplasmic proteins with N-acetyl-D-glucosamine (GlcNAc) moieties 482:553 Tau has been shown to be modified with O-linked N-acetylglucosamine residues (O-GlcNAc), which is the modification of serine and threonine residues of nucleocytoplasmic proteins with N-acetyl-D-glucosamine (GlcNAc) moieties. 27975253 6 23 theme modification 1056:1067 arg1 sites 1069:1073 O-GlcNAc modification sites 1047:1073 O-GlcNAc modification sites on tau including Ser400 1047:1097 These methods have enabled the identification of O-GlcNAc modification sites on tau including Ser400. 27975253 1 24 theme paired 167:172 arg1 filaments 182:190 paired helical filaments 167:190 paired helical filaments that ultimately give rise to neurofibrillary tangles (NFTs) 167:250 Assembly of the microtubule-associated protein tau (tau) into paired helical filaments that ultimately give rise to neurofibrillary tangles (NFTs) makes up one half of the two hallmark pathologies of Alzheimer's disease (AD). 27975253 3 25 theme tauopathy 595:603 arg1 models 585:590 mouse models 579:590 mouse models of tauopathy 579:603 Increasing O-GlcNAc in mouse models of tauopathy has been shown to hinder the progression of symptoms in these mice and impair the aggregation of tau into NFTs. 27975253 6 26 theme O-GlcNAc 1047:1054 arg1 sites 1069:1073 O-GlcNAc modification sites 1047:1073 O-GlcNAc modification sites on tau including Ser400 1047:1097 These methods have enabled the identification of O-GlcNAc modification sites on tau including Ser400. 27975253 1 27 theme helical 174:180 arg1 filaments 182:190 paired helical filaments 167:190 paired helical filaments that ultimately give rise to neurofibrillary tangles (NFTs) 167:250 Assembly of the microtubule-associated protein tau (tau) into paired helical filaments that ultimately give rise to neurofibrillary tangles (NFTs) makes up one half of the two hallmark pathologies of Alzheimer's disease (AD). 27975253 0 28 theme Tau 44:46 arg1 Detection 63:71 Detection 63:71 Detection of Ser400 O-GlcNAc Tau In Vivo 63:102 Production of O-GlcNAc Modified Recombinant Tau in E. coli and Detection of Ser400 O-GlcNAc Tau In Vivo. 27975253 0 28 theme Tau 44:46 arg1 Production 0:9 Production 0:9 Production of O-GlcNAc Modified Recombinant Tau in E. coli 0:57 Production of O-GlcNAc Modified Recombinant Tau in E. coli and Detection of Ser400 O-GlcNAc Tau In Vivo. 27975253 6 29 from tau 1078:1080 arg1 identification 1029:1042 the identification 1025:1042 the identification of O-GlcNAc modification sites on tau including Ser400 1025:1097 These methods have enabled the identification of O-GlcNAc modification sites on tau including Ser400. 27975253 0 30 from Detection 63:71 arg1 coli 54:57 E. coli 51:57 E. coli 51:57 Production of O-GlcNAc Modified Recombinant Tau in E. coli and Detection of Ser400 O-GlcNAc Tau In Vivo. 27975253 6 31 from sites 1069:1073 arg1 Ser400 1092:1097 Ser400 1092:1097 Ser400 1092:1097 These methods have enabled the identification of O-GlcNAc modification sites on tau including Ser400. 27975253 6 31 from sites 1069:1073 arg1 tau 1078:1080 tau 1078:1080 tau including Ser400 1078:1097 These methods have enabled the identification of O-GlcNAc modification sites on tau including Ser400. 27975253 0 32 theme Recombinant 32:42 arg1 Tau 44:46 O-GlcNAc Modified Recombinant Tau 14:46 O-GlcNAc Modified Recombinant Tau 14:46 Production of O-GlcNAc Modified Recombinant Tau in E. coli and Detection of Ser400 O-GlcNAc Tau In Vivo. 27975253 3 33 from progression 634:644 arg1 mice 667:670 these mice 661:670 these mice 661:670 Increasing O-GlcNAc in mouse models of tauopathy has been shown to hinder the progression of symptoms in these mice and impair the aggregation of tau into NFTs. 27975253 2 34 theme threonine 460:468 arg1 residues 399:406 O-linked N-acetylglucosamine residues 370:406 O-linked N-acetylglucosamine residues (O-GlcNAc) 370:417 Tau has been shown to be modified with O-linked N-acetylglucosamine residues (O-GlcNAc), which is the modification of serine and threonine residues of nucleocytoplasmic proteins with N-acetyl-D-glucosamine (GlcNAc) moieties. 27975253 2 34 theme threonine 460:468 arg1 modification 433:444 the modification 429:444 the modification of serine and threonine residues of nucleocytoplasmic proteins with N-acetyl-D-glucosamine (GlcNAc) moieties 429:553 Tau has been shown to be modified with O-linked N-acetylglucosamine residues (O-GlcNAc), which is the modification of serine and threonine residues of nucleocytoplasmic proteins with N-acetyl-D-glucosamine (GlcNAc) moieties. 27975253 4 35 theme modified 867:874 arg1 tau 876:878 O-GlcNAc modified tau 858:878 O-GlcNAc modified tau 858:878 In order to study how O-GlcNAc on tau may contribute to the protective effects observed in tauopathy mouse models, it is beneficial to study O-GlcNAc modified tau in vitro. 27975253 4 36 theme mouse 818:822 arg1 models 824:829 tauopathy mouse models 808:829 tauopathy mouse models 808:829 In order to study how O-GlcNAc on tau may contribute to the protective effects observed in tauopathy mouse models, it is beneficial to study O-GlcNAc modified tau in vitro. 27975253 2 37 dep serine 449:454 arg1 residues 470:477 residues 470:477 residues 470:477 Tau has been shown to be modified with O-linked N-acetylglucosamine residues (O-GlcNAc), which is the modification of serine and threonine residues of nucleocytoplasmic proteins with N-acetyl-D-glucosamine (GlcNAc) moieties. 27975253 3 38 theme tau 702:704 arg1 aggregation 687:697 the aggregation 683:697 the aggregation of tau into NFTs 683:714 Increasing O-GlcNAc in mouse models of tauopathy has been shown to hinder the progression of symptoms in these mice and impair the aggregation of tau into NFTs. 27975253 2 39 theme N-acetyl-D-glucosamine 514:535 arg1 moieties 546:553 N-acetyl-D-glucosamine (GlcNAc) moieties 514:553 N-acetyl-D-glucosamine (GlcNAc) moieties 514:553 Tau has been shown to be modified with O-linked N-acetylglucosamine residues (O-GlcNAc), which is the modification of serine and threonine residues of nucleocytoplasmic proteins with N-acetyl-D-glucosamine (GlcNAc) moieties. 27975253 7 40 from detection 1124:1132 arg1 tau 1156:1158 tau 1156:1158 tau from brain lysates 1156:1177 We further describe the detection of Ser400 O-GlcNAc on tau from brain lysates. 27975253 4 41 from O-GlcNAc 739:746 arg1 tau 751:753 tau 751:753 tau 751:753 In order to study how O-GlcNAc on tau may contribute to the protective effects observed in tauopathy mouse models, it is beneficial to study O-GlcNAc modified tau in vitro. 27975253 5 42 theme enriching 945:953 arg1 tau 967:969 enriching recombinant tau 945:969 enriching recombinant tau 945:969 Here we describe a method for producing, purifying and enriching recombinant tau that is O-GlcNAc modified. 27975253 6 43 from identification 1029:1042 arg1 Ser400 1092:1097 Ser400 1092:1097 Ser400 1092:1097 These methods have enabled the identification of O-GlcNAc modification sites on tau including Ser400. 27975253 6 43 from identification 1029:1042 arg1 tau 1078:1080 tau 1078:1080 tau including Ser400 1078:1097 These methods have enabled the identification of O-GlcNAc modification sites on tau including Ser400. 27975253 2 44 theme proteins 500:507 arg1 residues 399:406 O-linked N-acetylglucosamine residues 370:406 O-linked N-acetylglucosamine residues (O-GlcNAc) 370:417 Tau has been shown to be modified with O-linked N-acetylglucosamine residues (O-GlcNAc), which is the modification of serine and threonine residues of nucleocytoplasmic proteins with N-acetyl-D-glucosamine (GlcNAc) moieties. 27975253 2 44 theme proteins 500:507 arg1 modification 433:444 the modification 429:444 the modification of serine and threonine residues of nucleocytoplasmic proteins with N-acetyl-D-glucosamine (GlcNAc) moieties 429:553 Tau has been shown to be modified with O-linked N-acetylglucosamine residues (O-GlcNAc), which is the modification of serine and threonine residues of nucleocytoplasmic proteins with N-acetyl-D-glucosamine (GlcNAc) moieties. 27975253 5 45 theme recombinant 955:965 arg1 tau 967:969 enriching recombinant tau 945:969 enriching recombinant tau 945:969 Here we describe a method for producing, purifying and enriching recombinant tau that is O-GlcNAc modified. 27975253 3 46 theme mouse 579:583 arg1 models 585:590 mouse models 579:590 mouse models of tauopathy 579:603 Increasing O-GlcNAc in mouse models of tauopathy has been shown to hinder the progression of symptoms in these mice and impair the aggregation of tau into NFTs. 27975253 7 47 theme brain 1165:1169 arg1 lysates 1171:1177 brain lysates 1165:1177 brain lysates 1165:1177 We further describe the detection of Ser400 O-GlcNAc on tau from brain lysates. 27975253 4 48 located observed 796:803 arg1 models 824:829 tauopathy mouse models 808:829 tauopathy mouse models 808:829 In order to study how O-GlcNAc on tau may contribute to the protective effects observed in tauopathy mouse models, it is beneficial to study O-GlcNAc modified tau in vitro. 27975253 4 48 located observed 796:803 arg2 effects 788:794 the protective effects 773:794 the protective effects observed in tauopathy mouse models 773:829 In order to study how O-GlcNAc on tau may contribute to the protective effects observed in tauopathy mouse models, it is beneficial to study O-GlcNAc modified tau in vitro. 27975253 7 49 theme Ser400 1137:1142 arg1 O-GlcNAc 1144:1151 Ser400 O-GlcNAc 1137:1151 Ser400 O-GlcNAc 1137:1151 We further describe the detection of Ser400 O-GlcNAc on tau from brain lysates. 27975253 3 50 theme Increasing 556:565 arg1 O-GlcNAc 567:574 Increasing O-GlcNAc 556:574 Increasing O-GlcNAc in mouse models of tauopathy 556:603 Increasing O-GlcNAc in mouse models of tauopathy has been shown to hinder the progression of symptoms in these mice and impair the aggregation of tau into NFTs. 27975253 7 51 theme O-GlcNAc 1144:1151 arg1 detection 1124:1132 the detection 1120:1132 the detection of Ser400 O-GlcNAc on tau from brain lysates 1120:1177 We further describe the detection of Ser400 O-GlcNAc on tau from brain lysates. 27975253 1 52 theme hallmark 281:288 arg1 pathologies 290:300 the two hallmark pathologies 273:300 the two hallmark pathologies of Alzheimer's disease (AD) 273:328 Assembly of the microtubule-associated protein tau (tau) into paired helical filaments that ultimately give rise to neurofibrillary tangles (NFTs) makes up one half of the two hallmark pathologies of Alzheimer's disease (AD). 27975253 1 53 theme microtubule-associated 121:142 arg1 tau 157:159 the microtubule-associated protein tau (tau) 117:160 the microtubule-associated protein tau (tau) 117:160 Assembly of the microtubule-associated protein tau (tau) into paired helical filaments that ultimately give rise to neurofibrillary tangles (NFTs) makes up one half of the two hallmark pathologies of Alzheimer's disease (AD). 27975253 2 54 theme serine 449:454 arg1 residues 399:406 O-linked N-acetylglucosamine residues 370:406 O-linked N-acetylglucosamine residues (O-GlcNAc) 370:417 Tau has been shown to be modified with O-linked N-acetylglucosamine residues (O-GlcNAc), which is the modification of serine and threonine residues of nucleocytoplasmic proteins with N-acetyl-D-glucosamine (GlcNAc) moieties. 27975253 2 54 theme serine 449:454 arg1 modification 433:444 the modification 429:444 the modification of serine and threonine residues of nucleocytoplasmic proteins with N-acetyl-D-glucosamine (GlcNAc) moieties 429:553 Tau has been shown to be modified with O-linked N-acetylglucosamine residues (O-GlcNAc), which is the modification of serine and threonine residues of nucleocytoplasmic proteins with N-acetyl-D-glucosamine (GlcNAc) moieties. 27903134 4 0 theme high 943:946 arg1 stoichiometry 948:960 a high stoichiometry 941:960 a high stoichiometry 941:960 It was also confirmed that EWS, but not FUS and TAF15, is glycosylated with a high stoichiometry not only in the neural cells but also in the non-neural cell lines tested. 27903134 3 1 gly glycosylated 774:785 arg1 EWS 755:757 only EWS 750:757 only EWS 750:757 Here, the O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation stoichiometry of the FET proteins was chemoenzymatically analyzed, and it was found that only EWS is dynamically glycosylated with a high stoichiometry in the neural cell lines tested and in mouse brain. 27903134 5 2 theme cell 1194:1197 arg1 lineages 1199:1206 cell lineages 1194:1206 cell lineages 1194:1206 These results indicate that O-GlcNAc glycosylation imparts a physicochemical property on EWS that is distinct from that of the other FET proteins in most of cell lineages or tissues. 27903134 3 3 theme cell 827:830 arg1 lines 832:836 the neural cell lines 816:836 the neural cell lines tested 816:843 Here, the O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation stoichiometry of the FET proteins was chemoenzymatically analyzed, and it was found that only EWS is dynamically glycosylated with a high stoichiometry in the neural cell lines tested and in mouse brain. 27903134 3 4 theme proteins 686:693 arg1 stoichiometry 661:673 the O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation stoichiometry 601:673 the O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation stoichiometry of the FET proteins 601:693 Here, the O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation stoichiometry of the FET proteins was chemoenzymatically analyzed, and it was found that only EWS is dynamically glycosylated with a high stoichiometry in the neural cell lines tested and in mouse brain. 27903134 5 5 from property 1114:1121 arg1 EWS 1126:1128 EWS 1126:1128 EWS 1126:1128 These results indicate that O-GlcNAc glycosylation imparts a physicochemical property on EWS that is distinct from that of the other FET proteins in most of cell lineages or tissues. 27903134 4 6 theme non-neural 1007:1016 arg1 lines 1023:1027 the non-neural cell lines 1003:1027 the non-neural cell lines tested 1003:1034 It was also confirmed that EWS, but not FUS and TAF15, is glycosylated with a high stoichiometry not only in the neural cells but also in the non-neural cell lines tested. 27903134 2 7 theme proteins 509:516 arg1 dysregulation 488:500 dysregulation 488:500 dysregulation of FET proteins at the post-translational level 488:548 It is speculated that dysregulation of FET proteins at the post-translational level is involved in their cytoplasmic deposition. 27903134 1 8 theme frontotemporal 411:424 arg1 degeneration 432:443 frontotemporal lobar degeneration 411:443 frontotemporal lobar degeneration associated with FUS 411:463 Of the FET (fused in sarcoma [FUS]/Ewing sarcoma protein [EWS]/TATA binding protein-associated factor 15 [TAF15]) family of heterogeneous nuclear ribonucleoprotein particle proteins, FUS and TAF15 are consistently and EWS variably found in inclusion bodies in neurodegenerative diseases such as frontotemporal lobar degeneration associated with FUS. 27903134 4 9 gly glycosylated 923:934 arg2 EWS 892:894 EWS 892:894 EWS 892:894 It was also confirmed that EWS, but not FUS and TAF15, is glycosylated with a high stoichiometry not only in the neural cells but also in the non-neural cell lines tested. 27903134 4 9 gly glycosylated 923:934 arg1 FUS 905:907 FUS 905:907 FUS 905:907 It was also confirmed that EWS, but not FUS and TAF15, is glycosylated with a high stoichiometry not only in the neural cells but also in the non-neural cell lines tested. 27903134 4 9 gly glycosylated 923:934 arg2 FUS 905:907 FUS 905:907 FUS 905:907 It was also confirmed that EWS, but not FUS and TAF15, is glycosylated with a high stoichiometry not only in the neural cells but also in the non-neural cell lines tested. 27903134 4 9 gly glycosylated 923:934 arg1 EWS 892:894 EWS 892:894 EWS 892:894 It was also confirmed that EWS, but not FUS and TAF15, is glycosylated with a high stoichiometry not only in the neural cells but also in the non-neural cell lines tested. 27903134 4 9 gly glycosylated 923:934 arg1 cells 985:989 the neural cells 974:989 the neural cells 974:989 It was also confirmed that EWS, but not FUS and TAF15, is glycosylated with a high stoichiometry not only in the neural cells but also in the non-neural cell lines tested. 27903134 4 9 gly glycosylated 923:934 arg1 lines 1023:1027 the non-neural cell lines 1003:1027 the non-neural cell lines tested 1003:1034 It was also confirmed that EWS, but not FUS and TAF15, is glycosylated with a high stoichiometry not only in the neural cells but also in the non-neural cell lines tested. 27903134 1 10 from bodies 366:371 arg1 degeneration 432:443 frontotemporal lobar degeneration 411:443 frontotemporal lobar degeneration associated with FUS 411:463 Of the FET (fused in sarcoma [FUS]/Ewing sarcoma protein [EWS]/TATA binding protein-associated factor 15 [TAF15]) family of heterogeneous nuclear ribonucleoprotein particle proteins, FUS and TAF15 are consistently and EWS variably found in inclusion bodies in neurodegenerative diseases such as frontotemporal lobar degeneration associated with FUS. 27903134 1 10 from bodies 366:371 arg1 diseases 394:401 neurodegenerative diseases 376:401 neurodegenerative diseases such as frontotemporal lobar degeneration associated with FUS 376:463 Of the FET (fused in sarcoma [FUS]/Ewing sarcoma protein [EWS]/TATA binding protein-associated factor 15 [TAF15]) family of heterogeneous nuclear ribonucleoprotein particle proteins, FUS and TAF15 are consistently and EWS variably found in inclusion bodies in neurodegenerative diseases such as frontotemporal lobar degeneration associated with FUS. 27903134 2 11 theme cytoplasmic 571:581 arg1 deposition 583:592 their cytoplasmic deposition 565:592 their cytoplasmic deposition 565:592 It is speculated that dysregulation of FET proteins at the post-translational level is involved in their cytoplasmic deposition. 27903134 1 12 theme lobar 426:430 arg1 degeneration 432:443 frontotemporal lobar degeneration 411:443 frontotemporal lobar degeneration associated with FUS 411:463 Of the FET (fused in sarcoma [FUS]/Ewing sarcoma protein [EWS]/TATA binding protein-associated factor 15 [TAF15]) family of heterogeneous nuclear ribonucleoprotein particle proteins, FUS and TAF15 are consistently and EWS variably found in inclusion bodies in neurodegenerative diseases such as frontotemporal lobar degeneration associated with FUS. 27903134 3 13 theme neural 820:825 arg1 lines 832:836 the neural cell lines 816:836 the neural cell lines tested 816:843 Here, the O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation stoichiometry of the FET proteins was chemoenzymatically analyzed, and it was found that only EWS is dynamically glycosylated with a high stoichiometry in the neural cell lines tested and in mouse brain. 27903134 0 14 theme high 96:99 arg1 stoichiometry 101:113 a high stoichiometry 94:113 a high stoichiometry 94:113 O-GlcNAc glycosylation stoichiometry of the FET protein family: only EWS is glycosylated with a high stoichiometry. 27903134 1 15 theme sarcoma 137:143 arg1 [FUS 145:148 sarcoma [FUS 137:148 sarcoma [FUS 137:148 Of the FET (fused in sarcoma [FUS]/Ewing sarcoma protein [EWS]/TATA binding protein-associated factor 15 [TAF15]) family of heterogeneous nuclear ribonucleoprotein particle proteins, FUS and TAF15 are consistently and EWS variably found in inclusion bodies in neurodegenerative diseases such as frontotemporal lobar degeneration associated with FUS. 27903134 5 16 theme other 1164:1168 arg1 proteins 1174:1181 the other FET proteins 1160:1181 the other FET proteins in most of cell lineages or tissues 1160:1217 These results indicate that O-GlcNAc glycosylation imparts a physicochemical property on EWS that is distinct from that of the other FET proteins in most of cell lineages or tissues. 27903134 0 17 dep glycosylated 76:87 arg1 stoichiometry 23:35 O-GlcNAc glycosylation stoichiometry 0:35 O-GlcNAc glycosylation stoichiometry of the FET protein family 0:61 O-GlcNAc glycosylation stoichiometry of the FET protein family: only EWS is glycosylated with a high stoichiometry. 27903134 5 18 theme FET 1170:1172 arg1 proteins 1174:1181 the other FET proteins 1160:1181 the other FET proteins in most of cell lineages or tissues 1160:1217 These results indicate that O-GlcNAc glycosylation imparts a physicochemical property on EWS that is distinct from that of the other FET proteins in most of cell lineages or tissues. 27903134 1 19 located found 347:351 arg2 FUS 299:301 FUS 299:301 FUS 299:301 Of the FET (fused in sarcoma [FUS]/Ewing sarcoma protein [EWS]/TATA binding protein-associated factor 15 [TAF15]) family of heterogeneous nuclear ribonucleoprotein particle proteins, FUS and TAF15 are consistently and EWS variably found in inclusion bodies in neurodegenerative diseases such as frontotemporal lobar degeneration associated with FUS. 27903134 1 19 located found 347:351 arg1 bodies 366:371 inclusion bodies 356:371 inclusion bodies in neurodegenerative diseases such as frontotemporal lobar degeneration associated with FUS 356:463 Of the FET (fused in sarcoma [FUS]/Ewing sarcoma protein [EWS]/TATA binding protein-associated factor 15 [TAF15]) family of heterogeneous nuclear ribonucleoprotein particle proteins, FUS and TAF15 are consistently and EWS variably found in inclusion bodies in neurodegenerative diseases such as frontotemporal lobar degeneration associated with FUS. 27903134 1 19 located found 347:351 arg2 TAF15 307:311 TAF15 307:311 TAF15 307:311 Of the FET (fused in sarcoma [FUS]/Ewing sarcoma protein [EWS]/TATA binding protein-associated factor 15 [TAF15]) family of heterogeneous nuclear ribonucleoprotein particle proteins, FUS and TAF15 are consistently and EWS variably found in inclusion bodies in neurodegenerative diseases such as frontotemporal lobar degeneration associated with FUS. 27903134 0 20 theme glycosylation 9:21 arg1 stoichiometry 23:35 O-GlcNAc glycosylation stoichiometry 0:35 O-GlcNAc glycosylation stoichiometry of the FET protein family 0:61 O-GlcNAc glycosylation stoichiometry of the FET protein family: only EWS is glycosylated with a high stoichiometry. 27903134 0 21 gly glycosylated 76:87 arg1 EWS 69:71 only EWS 64:71 only EWS 64:71 O-GlcNAc glycosylation stoichiometry of the FET protein family: only EWS is glycosylated with a high stoichiometry. 27903134 0 22 theme O-GlcNAc 0:7 arg1 stoichiometry 23:35 O-GlcNAc glycosylation stoichiometry 0:35 O-GlcNAc glycosylation stoichiometry of the FET protein family 0:61 O-GlcNAc glycosylation stoichiometry of the FET protein family: only EWS is glycosylated with a high stoichiometry. 27903134 3 23 theme only 750:753 arg1 EWS 755:757 only EWS 750:757 only EWS 750:757 Here, the O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation stoichiometry of the FET proteins was chemoenzymatically analyzed, and it was found that only EWS is dynamically glycosylated with a high stoichiometry in the neural cell lines tested and in mouse brain. 27903134 3 24 link O-linked 605:612 arg1 stoichiometry 661:673 the O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation stoichiometry 601:673 the O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation stoichiometry of the FET proteins 601:693 Here, the O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation stoichiometry of the FET proteins was chemoenzymatically analyzed, and it was found that only EWS is dynamically glycosylated with a high stoichiometry in the neural cell lines tested and in mouse brain. 27903134 1 25 theme sarcoma 157:163 arg1 factor 211:216 sarcoma protein [EWS]/TATA binding protein-associated factor 15 157:219 sarcoma protein [EWS]/TATA binding protein-associated factor 15 [TAF15 157:226 Of the FET (fused in sarcoma [FUS]/Ewing sarcoma protein [EWS]/TATA binding protein-associated factor 15 [TAF15]) family of heterogeneous nuclear ribonucleoprotein particle proteins, FUS and TAF15 are consistently and EWS variably found in inclusion bodies in neurodegenerative diseases such as frontotemporal lobar degeneration associated with FUS. 27903134 1 26 theme heterogeneous 240:252 arg1 ribonucleoprotein 262:278 heterogeneous nuclear ribonucleoprotein 240:278 heterogeneous nuclear ribonucleoprotein particle proteins 240:296 Of the FET (fused in sarcoma [FUS]/Ewing sarcoma protein [EWS]/TATA binding protein-associated factor 15 [TAF15]) family of heterogeneous nuclear ribonucleoprotein particle proteins, FUS and TAF15 are consistently and EWS variably found in inclusion bodies in neurodegenerative diseases such as frontotemporal lobar degeneration associated with FUS. 27903134 2 27 theme post-translational 525:542 arg1 level 544:548 the post-translational level 521:548 the post-translational level 521:548 It is speculated that dysregulation of FET proteins at the post-translational level is involved in their cytoplasmic deposition. 27903134 1 28 theme protein 165:171 arg1 factor 211:216 sarcoma protein [EWS]/TATA binding protein-associated factor 15 157:219 sarcoma protein [EWS]/TATA binding protein-associated factor 15 [TAF15 157:226 Of the FET (fused in sarcoma [FUS]/Ewing sarcoma protein [EWS]/TATA binding protein-associated factor 15 [TAF15]) family of heterogeneous nuclear ribonucleoprotein particle proteins, FUS and TAF15 are consistently and EWS variably found in inclusion bodies in neurodegenerative diseases such as frontotemporal lobar degeneration associated with FUS. 27903134 0 29 theme FET 44:46 arg1 family 56:61 the FET protein family 40:61 the FET protein family 40:61 O-GlcNAc glycosylation stoichiometry of the FET protein family: only EWS is glycosylated with a high stoichiometry. 27903134 1 30 theme nuclear 254:260 arg1 ribonucleoprotein 262:278 heterogeneous nuclear ribonucleoprotein 240:278 heterogeneous nuclear ribonucleoprotein particle proteins 240:296 Of the FET (fused in sarcoma [FUS]/Ewing sarcoma protein [EWS]/TATA binding protein-associated factor 15 [TAF15]) family of heterogeneous nuclear ribonucleoprotein particle proteins, FUS and TAF15 are consistently and EWS variably found in inclusion bodies in neurodegenerative diseases such as frontotemporal lobar degeneration associated with FUS. 27903134 5 31 from that 1152:1155 arg1 distinct 1138:1145 distinct 1138:1145 distinct 1138:1145 These results indicate that O-GlcNAc glycosylation imparts a physicochemical property on EWS that is distinct from that of the other FET proteins in most of cell lineages or tissues. 27903134 5 31 from that 1152:1155 arg1 property 1114:1121 a physicochemical property 1096:1121 a physicochemical property on EWS that is distinct from that of the other FET proteins in most of cell lineages or tissues 1096:1217 These results indicate that O-GlcNAc glycosylation imparts a physicochemical property on EWS that is distinct from that of the other FET proteins in most of cell lineages or tissues. 27903134 3 32 theme glycosylation 647:659 arg1 stoichiometry 661:673 the O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation stoichiometry 601:673 the O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation stoichiometry of the FET proteins 601:693 Here, the O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation stoichiometry of the FET proteins was chemoenzymatically analyzed, and it was found that only EWS is dynamically glycosylated with a high stoichiometry in the neural cell lines tested and in mouse brain. 27903134 1 33 theme [EWS 173:176 arg1 factor 211:216 sarcoma protein [EWS]/TATA binding protein-associated factor 15 157:219 sarcoma protein [EWS]/TATA binding protein-associated factor 15 [TAF15 157:226 Of the FET (fused in sarcoma [FUS]/Ewing sarcoma protein [EWS]/TATA binding protein-associated factor 15 [TAF15]) family of heterogeneous nuclear ribonucleoprotein particle proteins, FUS and TAF15 are consistently and EWS variably found in inclusion bodies in neurodegenerative diseases such as frontotemporal lobar degeneration associated with FUS. 27903134 1 34 theme ribonucleoprotein 262:278 arg1 proteins 289:296 heterogeneous nuclear ribonucleoprotein particle proteins 240:296 heterogeneous nuclear ribonucleoprotein particle proteins 240:296 Of the FET (fused in sarcoma [FUS]/Ewing sarcoma protein [EWS]/TATA binding protein-associated factor 15 [TAF15]) family of heterogeneous nuclear ribonucleoprotein particle proteins, FUS and TAF15 are consistently and EWS variably found in inclusion bodies in neurodegenerative diseases such as frontotemporal lobar degeneration associated with FUS. 27903134 1 35 theme inclusion 356:364 arg1 bodies 366:371 inclusion bodies 356:371 inclusion bodies in neurodegenerative diseases such as frontotemporal lobar degeneration associated with FUS 356:463 Of the FET (fused in sarcoma [FUS]/Ewing sarcoma protein [EWS]/TATA binding protein-associated factor 15 [TAF15]) family of heterogeneous nuclear ribonucleoprotein particle proteins, FUS and TAF15 are consistently and EWS variably found in inclusion bodies in neurodegenerative diseases such as frontotemporal lobar degeneration associated with FUS. 27903134 2 36 from level 544:548 arg1 dysregulation 488:500 dysregulation 488:500 dysregulation of FET proteins at the post-translational level 488:548 It is speculated that dysregulation of FET proteins at the post-translational level is involved in their cytoplasmic deposition. 27903134 0 37 theme family 56:61 arg1 stoichiometry 23:35 O-GlcNAc glycosylation stoichiometry 0:35 O-GlcNAc glycosylation stoichiometry of the FET protein family 0:61 O-GlcNAc glycosylation stoichiometry of the FET protein family: only EWS is glycosylated with a high stoichiometry. 27903134 1 38 theme particle 280:287 arg1 proteins 289:296 heterogeneous nuclear ribonucleoprotein particle proteins 240:296 heterogeneous nuclear ribonucleoprotein particle proteins 240:296 Of the FET (fused in sarcoma [FUS]/Ewing sarcoma protein [EWS]/TATA binding protein-associated factor 15 [TAF15]) family of heterogeneous nuclear ribonucleoprotein particle proteins, FUS and TAF15 are consistently and EWS variably found in inclusion bodies in neurodegenerative diseases such as frontotemporal lobar degeneration associated with FUS. 27903134 3 39 theme O-GlcNAc 637:644 arg1 stoichiometry 661:673 the O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation stoichiometry 601:673 the O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation stoichiometry of the FET proteins 601:693 Here, the O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation stoichiometry of the FET proteins was chemoenzymatically analyzed, and it was found that only EWS is dynamically glycosylated with a high stoichiometry in the neural cell lines tested and in mouse brain. 27903134 2 40 theme FET 505:507 arg1 proteins 509:516 FET proteins 505:516 FET proteins 505:516 It is speculated that dysregulation of FET proteins at the post-translational level is involved in their cytoplasmic deposition. 27903134 0 41 theme protein 48:54 arg1 family 56:61 the FET protein family 40:61 the FET protein family 40:61 O-GlcNAc glycosylation stoichiometry of the FET protein family: only EWS is glycosylated with a high stoichiometry. 27903134 1 42 theme proteins 289:296 arg1 family 230:235 the FET (fused in sarcoma [FUS]/Ewing sarcoma protein [EWS]/TATA binding protein-associated factor 15 [TAF15]) family 119:235 the FET (fused in sarcoma [FUS]/Ewing sarcoma protein [EWS]/TATA binding protein-associated factor 15 [TAF15]) family of heterogeneous nuclear ribonucleoprotein particle proteins 119:296 Of the FET (fused in sarcoma [FUS]/Ewing sarcoma protein [EWS]/TATA binding protein-associated factor 15 [TAF15]) family of heterogeneous nuclear ribonucleoprotein particle proteins, FUS and TAF15 are consistently and EWS variably found in inclusion bodies in neurodegenerative diseases such as frontotemporal lobar degeneration associated with FUS. 27903134 3 43 theme FET 682:684 arg1 proteins 686:693 the FET proteins 678:693 the FET proteins 678:693 Here, the O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation stoichiometry of the FET proteins was chemoenzymatically analyzed, and it was found that only EWS is dynamically glycosylated with a high stoichiometry in the neural cell lines tested and in mouse brain. 27903134 5 44 theme physicochemical 1098:1112 arg1 distinct 1138:1145 distinct 1138:1145 distinct 1138:1145 These results indicate that O-GlcNAc glycosylation imparts a physicochemical property on EWS that is distinct from that of the other FET proteins in most of cell lineages or tissues. 27903134 5 44 theme physicochemical 1098:1112 arg1 property 1114:1121 a physicochemical property 1096:1121 a physicochemical property on EWS that is distinct from that of the other FET proteins in most of cell lineages or tissues 1096:1217 These results indicate that O-GlcNAc glycosylation imparts a physicochemical property on EWS that is distinct from that of the other FET proteins in most of cell lineages or tissues. 27903134 1 45 dep variably 338:345 arg1 EWS 334:336 EWS 334:336 EWS 334:336 Of the FET (fused in sarcoma [FUS]/Ewing sarcoma protein [EWS]/TATA binding protein-associated factor 15 [TAF15]) family of heterogeneous nuclear ribonucleoprotein particle proteins, FUS and TAF15 are consistently and EWS variably found in inclusion bodies in neurodegenerative diseases such as frontotemporal lobar degeneration associated with FUS. 27903134 3 46 from stoichiometry 799:811 arg1 brain 858:862 mouse brain 852:862 mouse brain 852:862 Here, the O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation stoichiometry of the FET proteins was chemoenzymatically analyzed, and it was found that only EWS is dynamically glycosylated with a high stoichiometry in the neural cell lines tested and in mouse brain. 27903134 3 46 from stoichiometry 799:811 arg1 lines 832:836 the neural cell lines 816:836 the neural cell lines tested 816:843 Here, the O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation stoichiometry of the FET proteins was chemoenzymatically analyzed, and it was found that only EWS is dynamically glycosylated with a high stoichiometry in the neural cell lines tested and in mouse brain. 27903134 1 47 theme neurodegenerative 376:392 arg1 degeneration 432:443 frontotemporal lobar degeneration 411:443 frontotemporal lobar degeneration associated with FUS 411:463 Of the FET (fused in sarcoma [FUS]/Ewing sarcoma protein [EWS]/TATA binding protein-associated factor 15 [TAF15]) family of heterogeneous nuclear ribonucleoprotein particle proteins, FUS and TAF15 are consistently and EWS variably found in inclusion bodies in neurodegenerative diseases such as frontotemporal lobar degeneration associated with FUS. 27903134 1 47 theme neurodegenerative 376:392 arg1 diseases 394:401 neurodegenerative diseases 376:401 neurodegenerative diseases such as frontotemporal lobar degeneration associated with FUS 376:463 Of the FET (fused in sarcoma [FUS]/Ewing sarcoma protein [EWS]/TATA binding protein-associated factor 15 [TAF15]) family of heterogeneous nuclear ribonucleoprotein particle proteins, FUS and TAF15 are consistently and EWS variably found in inclusion bodies in neurodegenerative diseases such as frontotemporal lobar degeneration associated with FUS. 27903134 3 48 theme O-linked 605:612 arg1 stoichiometry 661:673 the O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation stoichiometry 601:673 the O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation stoichiometry of the FET proteins 601:693 Here, the O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation stoichiometry of the FET proteins was chemoenzymatically analyzed, and it was found that only EWS is dynamically glycosylated with a high stoichiometry in the neural cell lines tested and in mouse brain. 27903134 3 49 theme mouse 852:856 arg1 brain 858:862 mouse brain 852:862 mouse brain 852:862 Here, the O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation stoichiometry of the FET proteins was chemoenzymatically analyzed, and it was found that only EWS is dynamically glycosylated with a high stoichiometry in the neural cell lines tested and in mouse brain. 27903134 1 50 theme /TATA 178:182 arg1 factor 211:216 sarcoma protein [EWS]/TATA binding protein-associated factor 15 157:219 sarcoma protein [EWS]/TATA binding protein-associated factor 15 [TAF15 157:226 Of the FET (fused in sarcoma [FUS]/Ewing sarcoma protein [EWS]/TATA binding protein-associated factor 15 [TAF15]) family of heterogeneous nuclear ribonucleoprotein particle proteins, FUS and TAF15 are consistently and EWS variably found in inclusion bodies in neurodegenerative diseases such as frontotemporal lobar degeneration associated with FUS. 27903134 5 51 from proteins 1174:1181 arg1 lineages 1199:1206 cell lineages 1194:1206 cell lineages 1194:1206 These results indicate that O-GlcNAc glycosylation imparts a physicochemical property on EWS that is distinct from that of the other FET proteins in most of cell lineages or tissues. 27903134 5 51 from proteins 1174:1181 arg1 tissues 1211:1217 tissues 1211:1217 tissues 1211:1217 These results indicate that O-GlcNAc glycosylation imparts a physicochemical property on EWS that is distinct from that of the other FET proteins in most of cell lineages or tissues. 27903134 5 51 from proteins 1174:1181 arg1 most 1186:1189 most 1186:1189 most 1186:1189 These results indicate that O-GlcNAc glycosylation imparts a physicochemical property on EWS that is distinct from that of the other FET proteins in most of cell lineages or tissues. 27903134 3 52 theme β-N-acetylglucosamine 614:634 arg1 stoichiometry 661:673 the O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation stoichiometry 601:673 the O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation stoichiometry of the FET proteins 601:693 Here, the O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation stoichiometry of the FET proteins was chemoenzymatically analyzed, and it was found that only EWS is dynamically glycosylated with a high stoichiometry in the neural cell lines tested and in mouse brain. 27903134 1 53 theme binding 184:190 arg1 factor 211:216 sarcoma protein [EWS]/TATA binding protein-associated factor 15 157:219 sarcoma protein [EWS]/TATA binding protein-associated factor 15 [TAF15 157:226 Of the FET (fused in sarcoma [FUS]/Ewing sarcoma protein [EWS]/TATA binding protein-associated factor 15 [TAF15]) family of heterogeneous nuclear ribonucleoprotein particle proteins, FUS and TAF15 are consistently and EWS variably found in inclusion bodies in neurodegenerative diseases such as frontotemporal lobar degeneration associated with FUS. 27903134 1 54 theme FET 123:125 arg1 family 230:235 the FET (fused in sarcoma [FUS]/Ewing sarcoma protein [EWS]/TATA binding protein-associated factor 15 [TAF15]) family 119:235 the FET (fused in sarcoma [FUS]/Ewing sarcoma protein [EWS]/TATA binding protein-associated factor 15 [TAF15]) family of heterogeneous nuclear ribonucleoprotein particle proteins 119:296 Of the FET (fused in sarcoma [FUS]/Ewing sarcoma protein [EWS]/TATA binding protein-associated factor 15 [TAF15]) family of heterogeneous nuclear ribonucleoprotein particle proteins, FUS and TAF15 are consistently and EWS variably found in inclusion bodies in neurodegenerative diseases such as frontotemporal lobar degeneration associated with FUS. 27903134 4 55 theme cell 1018:1021 arg1 lines 1023:1027 the non-neural cell lines 1003:1027 the non-neural cell lines tested 1003:1034 It was also confirmed that EWS, but not FUS and TAF15, is glycosylated with a high stoichiometry not only in the neural cells but also in the non-neural cell lines tested. 27903134 1 56 theme protein-associated 192:209 arg1 factor 211:216 sarcoma protein [EWS]/TATA binding protein-associated factor 15 157:219 sarcoma protein [EWS]/TATA binding protein-associated factor 15 [TAF15 157:226 Of the FET (fused in sarcoma [FUS]/Ewing sarcoma protein [EWS]/TATA binding protein-associated factor 15 [TAF15]) family of heterogeneous nuclear ribonucleoprotein particle proteins, FUS and TAF15 are consistently and EWS variably found in inclusion bodies in neurodegenerative diseases such as frontotemporal lobar degeneration associated with FUS. 27903134 5 57 theme O-GlcNAc 1065:1072 arg1 glycosylation 1074:1086 O-GlcNAc glycosylation 1065:1086 O-GlcNAc glycosylation 1065:1086 These results indicate that O-GlcNAc glycosylation imparts a physicochemical property on EWS that is distinct from that of the other FET proteins in most of cell lineages or tissues. 27903134 3 58 theme high 794:797 arg1 stoichiometry 799:811 a high stoichiometry 792:811 a high stoichiometry in the neural cell lines tested and in mouse brain 792:862 Here, the O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation stoichiometry of the FET proteins was chemoenzymatically analyzed, and it was found that only EWS is dynamically glycosylated with a high stoichiometry in the neural cell lines tested and in mouse brain. 27903134 4 59 theme neural 978:983 arg1 cells 985:989 the neural cells 974:989 the neural cells 974:989 It was also confirmed that EWS, but not FUS and TAF15, is glycosylated with a high stoichiometry not only in the neural cells but also in the non-neural cell lines tested. 27903134 1 60 theme factor 211:216 arg1 [TAF15 221:226 sarcoma protein [EWS]/TATA binding protein-associated factor 15 [TAF15 157:226 sarcoma protein [EWS]/TATA binding protein-associated factor 15 [TAF15 157:226 Of the FET (fused in sarcoma [FUS]/Ewing sarcoma protein [EWS]/TATA binding protein-associated factor 15 [TAF15]) family of heterogeneous nuclear ribonucleoprotein particle proteins, FUS and TAF15 are consistently and EWS variably found in inclusion bodies in neurodegenerative diseases such as frontotemporal lobar degeneration associated with FUS. 27598152 3 0 dep mutants 503:509 arg1 An∆pmtB 521:527 An∆pmtB 521:527 An∆pmtB 521:527 Therefore, we investigated if this was the case for NaD1 and NaD2, by assessing the sensitivity of the three Aspergillus nidulans (An) O-mannosyltransferase (pmt) knockout (KO) mutants (An∆pmtA, An∆pmtB, and An∆pmtC). 27598152 3 0 dep mutants 503:509 arg1 An∆pmtC 534:540 An∆pmtC 534:540 An∆pmtC 534:540 Therefore, we investigated if this was the case for NaD1 and NaD2, by assessing the sensitivity of the three Aspergillus nidulans (An) O-mannosyltransferase (pmt) knockout (KO) mutants (An∆pmtA, An∆pmtB, and An∆pmtC). 27598152 3 0 dep mutants 503:509 arg1 mutants 503:509 O-mannosyltransferase (pmt) knockout (KO) mutants 461:509 the three Aspergillus nidulans (An) O-mannosyltransferase (pmt) knockout (KO) mutants (An∆pmtA, An∆pmtB, and An∆pmtC) 425:541 Therefore, we investigated if this was the case for NaD1 and NaD2, by assessing the sensitivity of the three Aspergillus nidulans (An) O-mannosyltransferase (pmt) knockout (KO) mutants (An∆pmtA, An∆pmtB, and An∆pmtC). 27598152 4 1 with interaction 683:693 arg1 chains 714:719 O-linked side chains 700:719 O-linked side chains 700:719 An∆pmtA was resistant to both defensins, while An∆pmtC was resistant to NaD2 only, suggesting NaD1 and NaD2 are unlikely to have a general interaction with O-linked side chains. 27598152 7 2 theme pathway 1058:1064 arg1 mutants 1066:1072 HOG pathway mutants 1054:1072 HOG pathway mutants 1054:1072 HOG pathway mutants were sensitive to both NaD1 and NaD2, while CWI pathway mutants only displayed sensitivity to NaD2. 27598152 2 3 theme plant 254:258 arg1 defensins 260:268 Some plant defensins 249:268 Some plant defensins 249:268 Some plant defensins interact with fungal cell wall O-glycosylated proteins. 27598152 5 4 theme NaD1 827:830 arg1 sensitivities 841:853 the NaD1 and NaD2 sensitivities 823:853 the NaD1 and NaD2 sensitivities of the Fusarium oxysporum f. sp 823:885 Further evidence of this difference in the antifungal mechanism was provided by the dissimilarity of the NaD1 and NaD2 sensitivities of the Fusarium oxysporum f. sp. 27598152 5 5 from mechanism 776:784 arg1 evidence 730:737 Further evidence 722:737 Further evidence of this difference in the antifungal mechanism 722:784 Further evidence of this difference in the antifungal mechanism was provided by the dissimilarity of the NaD1 and NaD2 sensitivities of the Fusarium oxysporum f. sp. 27598152 3 6 theme knockout 489:496 arg1 An∆pmtB 521:527 An∆pmtB 521:527 An∆pmtB 521:527 Therefore, we investigated if this was the case for NaD1 and NaD2, by assessing the sensitivity of the three Aspergillus nidulans (An) O-mannosyltransferase (pmt) knockout (KO) mutants (An∆pmtA, An∆pmtB, and An∆pmtC). 27598152 3 6 theme knockout 489:496 arg1 An∆pmtC 534:540 An∆pmtC 534:540 An∆pmtC 534:540 Therefore, we investigated if this was the case for NaD1 and NaD2, by assessing the sensitivity of the three Aspergillus nidulans (An) O-mannosyltransferase (pmt) knockout (KO) mutants (An∆pmtA, An∆pmtB, and An∆pmtC). 27598152 3 6 theme knockout 489:496 arg1 mutants 503:509 O-mannosyltransferase (pmt) knockout (KO) mutants 461:509 the three Aspergillus nidulans (An) O-mannosyltransferase (pmt) knockout (KO) mutants (An∆pmtA, An∆pmtB, and An∆pmtC) 425:541 Therefore, we investigated if this was the case for NaD1 and NaD2, by assessing the sensitivity of the three Aspergillus nidulans (An) O-mannosyltransferase (pmt) knockout (KO) mutants (An∆pmtA, An∆pmtB, and An∆pmtC). 27598152 1 7 theme fungal 231:236 arg1 pathogens 238:246 fungal pathogens 231:246 fungal pathogens 231:246 Nicotiana alata defensins 1 and 2 (NaD1 and NaD2) are plant defensins from the ornamental tobacco that have antifungal activity against a variety of fungal pathogens. 27598152 7 8 theme pathway 1122:1128 arg1 mutants 1130:1136 CWI pathway mutants 1118:1136 CWI pathway mutants 1118:1136 HOG pathway mutants were sensitive to both NaD1 and NaD2, while CWI pathway mutants only displayed sensitivity to NaD2. 27598152 6 9 from integrity 953:961 arg1 CWI 964:966 CWI 964:966 CWI 964:966 lycopersici (Fol) signalling knockout mutants from the cell wall integrity (CWI) and high osmolarity glycerol (HOG) mitogen-activated protein kinase (MAPK) pathways. 27598152 6 9 from integrity 953:961 arg1 mutants 926:932 knockout mutants 917:932 knockout mutants from the cell wall integrity (CWI) 917:967 lycopersici (Fol) signalling knockout mutants from the cell wall integrity (CWI) and high osmolarity glycerol (HOG) mitogen-activated protein kinase (MAPK) pathways. 27598152 6 9 from integrity 953:961 arg1 pathways 1044:1051 high osmolarity glycerol (HOG) mitogen-activated protein kinase (MAPK) pathways 973:1051 high osmolarity glycerol (HOG) mitogen-activated protein kinase (MAPK) pathways 973:1051 lycopersici (Fol) signalling knockout mutants from the cell wall integrity (CWI) and high osmolarity glycerol (HOG) mitogen-activated protein kinase (MAPK) pathways. 27598152 1 10 dep 1 108:108 arg1 NaD2 126:129 NaD2 126:129 NaD2 126:129 Nicotiana alata defensins 1 and 2 (NaD1 and NaD2) are plant defensins from the ornamental tobacco that have antifungal activity against a variety of fungal pathogens. 27598152 1 10 dep 1 108:108 arg1 NaD1 117:120 NaD1 117:120 NaD1 117:120 Nicotiana alata defensins 1 and 2 (NaD1 and NaD2) are plant defensins from the ornamental tobacco that have antifungal activity against a variety of fungal pathogens. 27598152 5 11 theme difference 747:756 arg1 evidence 730:737 Further evidence 722:737 Further evidence of this difference in the antifungal mechanism 722:784 Further evidence of this difference in the antifungal mechanism was provided by the dissimilarity of the NaD1 and NaD2 sensitivities of the Fusarium oxysporum f. sp. 27598152 7 12 theme HOG 1054:1056 arg1 mutants 1066:1072 HOG pathway mutants 1054:1072 HOG pathway mutants 1054:1072 HOG pathway mutants were sensitive to both NaD1 and NaD2, while CWI pathway mutants only displayed sensitivity to NaD2. 27598152 6 13 theme glycerol 989:996 arg1 MAPK 1038:1041 MAPK 1038:1041 MAPK 1038:1041 lycopersici (Fol) signalling knockout mutants from the cell wall integrity (CWI) and high osmolarity glycerol (HOG) mitogen-activated protein kinase (MAPK) pathways. 27598152 6 13 theme glycerol 989:996 arg1 kinase 1030:1035 high osmolarity glycerol (HOG) mitogen-activated protein kinase 973:1035 high osmolarity glycerol (HOG) mitogen-activated protein kinase (MAPK) pathways 973:1051 lycopersici (Fol) signalling knockout mutants from the cell wall integrity (CWI) and high osmolarity glycerol (HOG) mitogen-activated protein kinase (MAPK) pathways. 27598152 6 14 theme mitogen-activated 1004:1020 arg1 MAPK 1038:1041 MAPK 1038:1041 MAPK 1038:1041 lycopersici (Fol) signalling knockout mutants from the cell wall integrity (CWI) and high osmolarity glycerol (HOG) mitogen-activated protein kinase (MAPK) pathways. 27598152 6 14 theme mitogen-activated 1004:1020 arg1 kinase 1030:1035 high osmolarity glycerol (HOG) mitogen-activated protein kinase 973:1035 high osmolarity glycerol (HOG) mitogen-activated protein kinase (MAPK) pathways 973:1051 lycopersici (Fol) signalling knockout mutants from the cell wall integrity (CWI) and high osmolarity glycerol (HOG) mitogen-activated protein kinase (MAPK) pathways. 27598152 3 15 dep nidulans 447:454 arg1 An 457:458 An 457:458 An 457:458 Therefore, we investigated if this was the case for NaD1 and NaD2, by assessing the sensitivity of the three Aspergillus nidulans (An) O-mannosyltransferase (pmt) knockout (KO) mutants (An∆pmtA, An∆pmtB, and An∆pmtC). 27598152 3 15 dep nidulans 447:454 arg1 An∆pmtB 521:527 An∆pmtB 521:527 An∆pmtB 521:527 Therefore, we investigated if this was the case for NaD1 and NaD2, by assessing the sensitivity of the three Aspergillus nidulans (An) O-mannosyltransferase (pmt) knockout (KO) mutants (An∆pmtA, An∆pmtB, and An∆pmtC). 27598152 3 15 dep nidulans 447:454 arg1 An∆pmtC 534:540 An∆pmtC 534:540 An∆pmtC 534:540 Therefore, we investigated if this was the case for NaD1 and NaD2, by assessing the sensitivity of the three Aspergillus nidulans (An) O-mannosyltransferase (pmt) knockout (KO) mutants (An∆pmtA, An∆pmtB, and An∆pmtC). 27598152 3 15 dep nidulans 447:454 arg1 mutants 503:509 O-mannosyltransferase (pmt) knockout (KO) mutants 461:509 the three Aspergillus nidulans (An) O-mannosyltransferase (pmt) knockout (KO) mutants (An∆pmtA, An∆pmtB, and An∆pmtC) 425:541 Therefore, we investigated if this was the case for NaD1 and NaD2, by assessing the sensitivity of the three Aspergillus nidulans (An) O-mannosyltransferase (pmt) knockout (KO) mutants (An∆pmtA, An∆pmtB, and An∆pmtC). 27598152 1 16 theme plant 136:140 arg1 defensins 142:150 plant defensins 136:150 plant defensins from the ornamental tobacco that have antifungal activity against a variety of fungal pathogens 136:246 Nicotiana alata defensins 1 and 2 (NaD1 and NaD2) are plant defensins from the ornamental tobacco that have antifungal activity against a variety of fungal pathogens. 27598152 1 16 theme plant 136:140 arg1 defensins 98:106 Nicotiana alata defensins 1 and 2 (NaD1 and NaD2) 82:130 Nicotiana alata defensins 1 and 2 (NaD1 and NaD2) 82:130 Nicotiana alata defensins 1 and 2 (NaD1 and NaD2) are plant defensins from the ornamental tobacco that have antifungal activity against a variety of fungal pathogens. 27598152 6 17 theme kinase 1030:1035 arg1 pathways 1044:1051 high osmolarity glycerol (HOG) mitogen-activated protein kinase (MAPK) pathways 973:1051 high osmolarity glycerol (HOG) mitogen-activated protein kinase (MAPK) pathways 973:1051 lycopersici (Fol) signalling knockout mutants from the cell wall integrity (CWI) and high osmolarity glycerol (HOG) mitogen-activated protein kinase (MAPK) pathways. 27598152 2 18 theme fungal 284:289 arg1 proteins 316:323 fungal cell wall O-glycosylated proteins 284:323 fungal cell wall O-glycosylated proteins 284:323 Some plant defensins interact with fungal cell wall O-glycosylated proteins. 27598152 7 19 theme CWI 1118:1120 arg1 mutants 1130:1136 CWI pathway mutants 1118:1136 CWI pathway mutants 1118:1136 HOG pathway mutants were sensitive to both NaD1 and NaD2, while CWI pathway mutants only displayed sensitivity to NaD2. 27598152 6 20 theme wall 948:951 arg1 integrity 953:961 the cell wall integrity 939:961 the cell wall integrity 939:961 lycopersici (Fol) signalling knockout mutants from the cell wall integrity (CWI) and high osmolarity glycerol (HOG) mitogen-activated protein kinase (MAPK) pathways. 27598152 0 21 theme Plant 0:4 arg1 NaD1 16:19 NaD1 16:19 NaD1 16:19 Plant Defensins NaD1 and NaD2 Induce Different Stress Response Pathways in Fungi. 27598152 0 21 theme Plant 0:4 arg1 Defensins 6:14 Plant Defensins NaD1 and NaD2 0:28 Plant Defensins NaD1 and NaD2 0:28 Plant Defensins NaD1 and NaD2 Induce Different Stress Response Pathways in Fungi. 27598152 0 21 theme Plant 0:4 arg1 NaD2 25:28 NaD2 25:28 NaD2 25:28 Plant Defensins NaD1 and NaD2 Induce Different Stress Response Pathways in Fungi. 27598152 1 22 theme pathogens 238:246 arg1 variety 220:226 a variety 218:226 a variety of fungal pathogens 218:246 Nicotiana alata defensins 1 and 2 (NaD1 and NaD2) are plant defensins from the ornamental tobacco that have antifungal activity against a variety of fungal pathogens. 27598152 1 22 theme pathogens 238:246 arg1 pathogens 238:246 fungal pathogens 231:246 fungal pathogens 231:246 Nicotiana alata defensins 1 and 2 (NaD1 and NaD2) are plant defensins from the ornamental tobacco that have antifungal activity against a variety of fungal pathogens. 27598152 1 23 theme Nicotiana 82:90 arg1 defensins 142:150 plant defensins 136:150 plant defensins from the ornamental tobacco that have antifungal activity against a variety of fungal pathogens 136:246 Nicotiana alata defensins 1 and 2 (NaD1 and NaD2) are plant defensins from the ornamental tobacco that have antifungal activity against a variety of fungal pathogens. 27598152 1 23 theme Nicotiana 82:90 arg1 defensins 98:106 Nicotiana alata defensins 1 and 2 (NaD1 and NaD2) 82:130 Nicotiana alata defensins 1 and 2 (NaD1 and NaD2) 82:130 Nicotiana alata defensins 1 and 2 (NaD1 and NaD2) are plant defensins from the ornamental tobacco that have antifungal activity against a variety of fungal pathogens. 27598152 4 24 link O-linked 700:707 arg1 chains 714:719 O-linked side chains 700:719 O-linked side chains 700:719 An∆pmtA was resistant to both defensins, while An∆pmtC was resistant to NaD2 only, suggesting NaD1 and NaD2 are unlikely to have a general interaction with O-linked side chains. 27598152 3 25 dep knockout 489:496 arg1 KO 499:500 KO 499:500 KO 499:500 Therefore, we investigated if this was the case for NaD1 and NaD2, by assessing the sensitivity of the three Aspergillus nidulans (An) O-mannosyltransferase (pmt) knockout (KO) mutants (An∆pmtA, An∆pmtB, and An∆pmtC). 27598152 1 26 theme alata 92:96 arg1 defensins 142:150 plant defensins 136:150 plant defensins from the ornamental tobacco that have antifungal activity against a variety of fungal pathogens 136:246 Nicotiana alata defensins 1 and 2 (NaD1 and NaD2) are plant defensins from the ornamental tobacco that have antifungal activity against a variety of fungal pathogens. 27598152 1 26 theme alata 92:96 arg1 defensins 98:106 Nicotiana alata defensins 1 and 2 (NaD1 and NaD2) 82:130 Nicotiana alata defensins 1 and 2 (NaD1 and NaD2) 82:130 Nicotiana alata defensins 1 and 2 (NaD1 and NaD2) are plant defensins from the ornamental tobacco that have antifungal activity against a variety of fungal pathogens. 27598152 5 27 theme Further 722:728 arg1 evidence 730:737 Further evidence 722:737 Further evidence of this difference in the antifungal mechanism 722:784 Further evidence of this difference in the antifungal mechanism was provided by the dissimilarity of the NaD1 and NaD2 sensitivities of the Fusarium oxysporum f. sp. 27598152 6 28 theme protein 1022:1028 arg1 MAPK 1038:1041 MAPK 1038:1041 MAPK 1038:1041 lycopersici (Fol) signalling knockout mutants from the cell wall integrity (CWI) and high osmolarity glycerol (HOG) mitogen-activated protein kinase (MAPK) pathways. 27598152 6 28 theme protein 1022:1028 arg1 kinase 1030:1035 high osmolarity glycerol (HOG) mitogen-activated protein kinase 973:1035 high osmolarity glycerol (HOG) mitogen-activated protein kinase (MAPK) pathways 973:1051 lycopersici (Fol) signalling knockout mutants from the cell wall integrity (CWI) and high osmolarity glycerol (HOG) mitogen-activated protein kinase (MAPK) pathways. 27598152 5 29 theme Fusarium 862:869 arg1 sp 884:885 the Fusarium oxysporum f. sp 858:885 the Fusarium oxysporum f. sp 858:885 Further evidence of this difference in the antifungal mechanism was provided by the dissimilarity of the NaD1 and NaD2 sensitivities of the Fusarium oxysporum f. sp. 27598152 5 30 theme sensitivities 841:853 arg1 dissimilarity 806:818 the dissimilarity 802:818 the dissimilarity of the NaD1 and NaD2 sensitivities of the Fusarium oxysporum f. sp 802:885 Further evidence of this difference in the antifungal mechanism was provided by the dissimilarity of the NaD1 and NaD2 sensitivities of the Fusarium oxysporum f. sp. 27598152 1 31 theme ornamental 161:170 arg1 tobacco 172:178 the ornamental tobacco 157:178 the ornamental tobacco 157:178 Nicotiana alata defensins 1 and 2 (NaD1 and NaD2) are plant defensins from the ornamental tobacco that have antifungal activity against a variety of fungal pathogens. 27598152 3 32 theme nidulans 447:454 arg1 sensitivity 410:420 the sensitivity 406:420 the sensitivity of the three Aspergillus nidulans (An) O-mannosyltransferase (pmt) knockout (KO) mutants (An∆pmtA, An∆pmtB, and An∆pmtC) 406:541 Therefore, we investigated if this was the case for NaD1 and NaD2, by assessing the sensitivity of the three Aspergillus nidulans (An) O-mannosyltransferase (pmt) knockout (KO) mutants (An∆pmtA, An∆pmtB, and An∆pmtC). 27598152 4 33 theme side 709:712 arg1 chains 714:719 O-linked side chains 700:719 O-linked side chains 700:719 An∆pmtA was resistant to both defensins, while An∆pmtC was resistant to NaD2 only, suggesting NaD1 and NaD2 are unlikely to have a general interaction with O-linked side chains. 27598152 5 34 theme antifungal 765:774 arg1 mechanism 776:784 the antifungal mechanism 761:784 the antifungal mechanism 761:784 Further evidence of this difference in the antifungal mechanism was provided by the dissimilarity of the NaD1 and NaD2 sensitivities of the Fusarium oxysporum f. sp. 27598152 4 35 theme O-linked 700:707 arg1 chains 714:719 O-linked side chains 700:719 O-linked side chains 700:719 An∆pmtA was resistant to both defensins, while An∆pmtC was resistant to NaD2 only, suggesting NaD1 and NaD2 are unlikely to have a general interaction with O-linked side chains. 27598152 1 36 from tobacco 172:178 arg1 defensins 142:150 plant defensins 136:150 plant defensins from the ornamental tobacco that have antifungal activity against a variety of fungal pathogens 136:246 Nicotiana alata defensins 1 and 2 (NaD1 and NaD2) are plant defensins from the ornamental tobacco that have antifungal activity against a variety of fungal pathogens. 27598152 1 36 from tobacco 172:178 arg1 defensins 98:106 Nicotiana alata defensins 1 and 2 (NaD1 and NaD2) 82:130 Nicotiana alata defensins 1 and 2 (NaD1 and NaD2) 82:130 Nicotiana alata defensins 1 and 2 (NaD1 and NaD2) are plant defensins from the ornamental tobacco that have antifungal activity against a variety of fungal pathogens. 27598152 6 37 theme knockout 917:924 arg1 CWI 964:966 CWI 964:966 CWI 964:966 lycopersici (Fol) signalling knockout mutants from the cell wall integrity (CWI) and high osmolarity glycerol (HOG) mitogen-activated protein kinase (MAPK) pathways. 27598152 6 37 theme knockout 917:924 arg1 mutants 926:932 knockout mutants 917:932 knockout mutants from the cell wall integrity (CWI) 917:967 lycopersici (Fol) signalling knockout mutants from the cell wall integrity (CWI) and high osmolarity glycerol (HOG) mitogen-activated protein kinase (MAPK) pathways. 27598152 0 38 theme Stress 47:52 arg1 Pathways 63:70 Different Stress Response Pathways 37:70 Different Stress Response Pathways 37:70 Plant Defensins NaD1 and NaD2 Induce Different Stress Response Pathways in Fungi. 27598152 4 39 contain have 668:671 arg1 NaD2 647:650 NaD2 647:650 NaD2 647:650 An∆pmtA was resistant to both defensins, while An∆pmtC was resistant to NaD2 only, suggesting NaD1 and NaD2 are unlikely to have a general interaction with O-linked side chains. 27598152 4 39 contain have 668:671 arg1 NaD1 638:641 NaD1 638:641 NaD1 638:641 An∆pmtA was resistant to both defensins, while An∆pmtC was resistant to NaD2 only, suggesting NaD1 and NaD2 are unlikely to have a general interaction with O-linked side chains. 27598152 4 39 contain have 668:671 arg2 interaction 683:693 a general interaction 673:693 a general interaction with O-linked side chains 673:719 An∆pmtA was resistant to both defensins, while An∆pmtC was resistant to NaD2 only, suggesting NaD1 and NaD2 are unlikely to have a general interaction with O-linked side chains. 27598152 2 40 gly O-glycosylated 301:314 arg1 proteins 316:323 fungal cell wall O-glycosylated proteins 284:323 fungal cell wall O-glycosylated proteins 284:323 Some plant defensins interact with fungal cell wall O-glycosylated proteins. 27598152 3 41 theme Aspergillus 435:445 arg1 nidulans 447:454 the three Aspergillus nidulans 425:454 the three Aspergillus nidulans (An) O-mannosyltransferase (pmt) knockout (KO) mutants (An∆pmtA, An∆pmtB, and An∆pmtC) 425:541 Therefore, we investigated if this was the case for NaD1 and NaD2, by assessing the sensitivity of the three Aspergillus nidulans (An) O-mannosyltransferase (pmt) knockout (KO) mutants (An∆pmtA, An∆pmtB, and An∆pmtC). 27598152 0 42 theme Different 37:45 arg1 Pathways 63:70 Different Stress Response Pathways 37:70 Different Stress Response Pathways 37:70 Plant Defensins NaD1 and NaD2 Induce Different Stress Response Pathways in Fungi. 27598152 6 43 theme cell 943:946 arg1 integrity 953:961 the cell wall integrity 939:961 the cell wall integrity 939:961 lycopersici (Fol) signalling knockout mutants from the cell wall integrity (CWI) and high osmolarity glycerol (HOG) mitogen-activated protein kinase (MAPK) pathways. 27598152 1 44 contain have 185:188 arg1 defensins 142:150 plant defensins 136:150 plant defensins from the ornamental tobacco that have antifungal activity against a variety of fungal pathogens 136:246 Nicotiana alata defensins 1 and 2 (NaD1 and NaD2) are plant defensins from the ornamental tobacco that have antifungal activity against a variety of fungal pathogens. 27598152 1 44 contain have 185:188 arg1 defensins 98:106 Nicotiana alata defensins 1 and 2 (NaD1 and NaD2) 82:130 Nicotiana alata defensins 1 and 2 (NaD1 and NaD2) 82:130 Nicotiana alata defensins 1 and 2 (NaD1 and NaD2) are plant defensins from the ornamental tobacco that have antifungal activity against a variety of fungal pathogens. 27598152 1 44 contain have 185:188 arg2 activity 201:208 antifungal activity 190:208 antifungal activity 190:208 Nicotiana alata defensins 1 and 2 (NaD1 and NaD2) are plant defensins from the ornamental tobacco that have antifungal activity against a variety of fungal pathogens. 27598152 2 45 theme O-glycosylated 301:314 arg1 proteins 316:323 fungal cell wall O-glycosylated proteins 284:323 fungal cell wall O-glycosylated proteins 284:323 Some plant defensins interact with fungal cell wall O-glycosylated proteins. 27598152 5 46 theme f. 881:882 arg1 sp 884:885 the Fusarium oxysporum f. sp 858:885 the Fusarium oxysporum f. sp 858:885 Further evidence of this difference in the antifungal mechanism was provided by the dissimilarity of the NaD1 and NaD2 sensitivities of the Fusarium oxysporum f. sp. 27598152 4 47 theme general 675:681 arg1 interaction 683:693 a general interaction 673:693 a general interaction with O-linked side chains 673:719 An∆pmtA was resistant to both defensins, while An∆pmtC was resistant to NaD2 only, suggesting NaD1 and NaD2 are unlikely to have a general interaction with O-linked side chains. 27598152 5 48 from evidence 730:737 arg1 mechanism 776:784 the antifungal mechanism 761:784 the antifungal mechanism 761:784 Further evidence of this difference in the antifungal mechanism was provided by the dissimilarity of the NaD1 and NaD2 sensitivities of the Fusarium oxysporum f. sp. 27598152 2 49 theme wall 296:299 arg1 proteins 316:323 fungal cell wall O-glycosylated proteins 284:323 fungal cell wall O-glycosylated proteins 284:323 Some plant defensins interact with fungal cell wall O-glycosylated proteins. 27598152 5 50 theme NaD2 836:839 arg1 sensitivities 841:853 the NaD1 and NaD2 sensitivities 823:853 the NaD1 and NaD2 sensitivities of the Fusarium oxysporum f. sp 823:885 Further evidence of this difference in the antifungal mechanism was provided by the dissimilarity of the NaD1 and NaD2 sensitivities of the Fusarium oxysporum f. sp. 27598152 5 51 theme oxysporum 871:879 arg1 sp 884:885 the Fusarium oxysporum f. sp 858:885 the Fusarium oxysporum f. sp 858:885 Further evidence of this difference in the antifungal mechanism was provided by the dissimilarity of the NaD1 and NaD2 sensitivities of the Fusarium oxysporum f. sp. 27598152 5 52 theme sp 884:885 arg1 sensitivities 841:853 the NaD1 and NaD2 sensitivities 823:853 the NaD1 and NaD2 sensitivities of the Fusarium oxysporum f. sp 823:885 Further evidence of this difference in the antifungal mechanism was provided by the dissimilarity of the NaD1 and NaD2 sensitivities of the Fusarium oxysporum f. sp. 27598152 2 53 theme cell 291:294 arg1 proteins 316:323 fungal cell wall O-glycosylated proteins 284:323 fungal cell wall O-glycosylated proteins 284:323 Some plant defensins interact with fungal cell wall O-glycosylated proteins. 27598152 1 54 theme antifungal 190:199 arg1 activity 201:208 antifungal activity 190:208 antifungal activity 190:208 Nicotiana alata defensins 1 and 2 (NaD1 and NaD2) are plant defensins from the ornamental tobacco that have antifungal activity against a variety of fungal pathogens. 27598152 0 55 dep Defensins 6:14 arg1 NaD1 16:19 NaD1 16:19 NaD1 16:19 Plant Defensins NaD1 and NaD2 Induce Different Stress Response Pathways in Fungi. 27598152 0 55 dep Defensins 6:14 arg1 Defensins 6:14 Plant Defensins NaD1 and NaD2 0:28 Plant Defensins NaD1 and NaD2 0:28 Plant Defensins NaD1 and NaD2 Induce Different Stress Response Pathways in Fungi. 27598152 0 55 dep Defensins 6:14 arg1 NaD2 25:28 NaD2 25:28 NaD2 25:28 Plant Defensins NaD1 and NaD2 Induce Different Stress Response Pathways in Fungi. 27598152 6 56 theme high 973:976 arg1 glycerol 989:996 high osmolarity glycerol 973:996 high osmolarity glycerol (HOG) mitogen-activated protein kinase (MAPK) pathways 973:1051 lycopersici (Fol) signalling knockout mutants from the cell wall integrity (CWI) and high osmolarity glycerol (HOG) mitogen-activated protein kinase (MAPK) pathways. 27598152 6 56 theme high 973:976 arg1 HOG 999:1001 HOG 999:1001 HOG 999:1001 lycopersici (Fol) signalling knockout mutants from the cell wall integrity (CWI) and high osmolarity glycerol (HOG) mitogen-activated protein kinase (MAPK) pathways. 27598152 0 57 theme Response 54:61 arg1 Pathways 63:70 Different Stress Response Pathways 37:70 Different Stress Response Pathways 37:70 Plant Defensins NaD1 and NaD2 Induce Different Stress Response Pathways in Fungi. 27598152 6 58 theme osmolarity 978:987 arg1 glycerol 989:996 high osmolarity glycerol 973:996 high osmolarity glycerol (HOG) mitogen-activated protein kinase (MAPK) pathways 973:1051 lycopersici (Fol) signalling knockout mutants from the cell wall integrity (CWI) and high osmolarity glycerol (HOG) mitogen-activated protein kinase (MAPK) pathways. 27598152 6 58 theme osmolarity 978:987 arg1 HOG 999:1001 HOG 999:1001 HOG 999:1001 lycopersici (Fol) signalling knockout mutants from the cell wall integrity (CWI) and high osmolarity glycerol (HOG) mitogen-activated protein kinase (MAPK) pathways. 27598152 5 59 from difference 747:756 arg1 mechanism 776:784 the antifungal mechanism 761:784 the antifungal mechanism 761:784 Further evidence of this difference in the antifungal mechanism was provided by the dissimilarity of the NaD1 and NaD2 sensitivities of the Fusarium oxysporum f. sp. 27598152 1 60 dep defensins 98:106 arg1 2 114:114 2 114:114 2 114:114 Nicotiana alata defensins 1 and 2 (NaD1 and NaD2) are plant defensins from the ornamental tobacco that have antifungal activity against a variety of fungal pathogens. 27598152 1 60 dep defensins 98:106 arg1 1 108:108 1 108:108 1 108:108 Nicotiana alata defensins 1 and 2 (NaD1 and NaD2) are plant defensins from the ornamental tobacco that have antifungal activity against a variety of fungal pathogens. 28068756 4 0 gly glycopeptides 675:687 arg1 digests 723:729 horseradish peroxidase (HRP) digests 694:729 horseradish peroxidase (HRP) digests 694:729 A total of 25 glycopeptides from horseradish peroxidase (HRP) digests and 33 glycopeptides from IgG were identified, respectively. 28068756 4 0 gly glycopeptides 675:687 arg1 glycopeptides 738:750 33 glycopeptides 735:750 33 glycopeptides from IgG 735:759 A total of 25 glycopeptides from horseradish peroxidase (HRP) digests and 33 glycopeptides from IgG were identified, respectively. 28068756 4 0 gly glycopeptides 675:687 arg2 glycopeptides 675:687 25 glycopeptides 672:687 25 glycopeptides from horseradish peroxidase (HRP) digests and 33 glycopeptides from IgG 672:759 A total of 25 glycopeptides from horseradish peroxidase (HRP) digests and 33 glycopeptides from IgG were identified, respectively. 28068756 1 1 theme enrichment 168:177 arg1 chromatography 128:141 Hydrophilic interaction liquid chromatography 97:141 Hydrophilic interaction liquid chromatography (HILIC) 97:149 Hydrophilic interaction liquid chromatography (HILIC) is a significant enrichment strategy in glycoproteomics profiling. 28068756 1 1 theme enrichment 168:177 arg1 strategy 179:186 a significant enrichment strategy 154:186 a significant enrichment strategy in glycoproteomics profiling 154:215 Hydrophilic interaction liquid chromatography (HILIC) is a significant enrichment strategy in glycoproteomics profiling. 28068756 0 2 theme Glycopeptide 83:94 arg1 Enrichment 60:69 Highly Specific Enrichment 44:69 Highly Specific Enrichment of N-Linked Glycopeptide 44:94 Hydrophilic Mesoporous Silica Materials for Highly Specific Enrichment of N-Linked Glycopeptide. 28068756 4 3 from glycopeptides 738:750 arg1 total 663:667 A total 661:667 A total of 25 glycopeptides from horseradish peroxidase (HRP) digests and 33 glycopeptides from IgG 661:759 A total of 25 glycopeptides from horseradish peroxidase (HRP) digests and 33 glycopeptides from IgG were identified, respectively. 28068756 4 3 from glycopeptides 738:750 arg1 glycopeptides 675:687 25 glycopeptides 672:687 25 glycopeptides from horseradish peroxidase (HRP) digests and 33 glycopeptides from IgG 672:759 A total of 25 glycopeptides from horseradish peroxidase (HRP) digests and 33 glycopeptides from IgG were identified, respectively. 28068756 1 4 from strategy 179:186 arg1 profiling 207:215 glycoproteomics profiling 191:215 glycoproteomics profiling 191:215 Hydrophilic interaction liquid chromatography (HILIC) is a significant enrichment strategy in glycoproteomics profiling. 28068756 3 5 gly glycopeptides 539:551 arg2 glycopeptides 539:551 glycopeptides 539:551 glycopeptides 539:551 By taking advantage of their merits, such as large surface area, excellent hydrophilicity and unbiased affinity toward all types of glycopeptides, the Fe3O4@mSiO2-IDA nanomaterials were successfully applied to capture glycopeptides from complex samples. 28068756 3 6 theme @ 563:563 arg1 nanomaterials 574:586 the Fe3O4@mSiO2-IDA nanomaterials 554:586 the Fe3O4@mSiO2-IDA nanomaterials 554:586 By taking advantage of their merits, such as large surface area, excellent hydrophilicity and unbiased affinity toward all types of glycopeptides, the Fe3O4@mSiO2-IDA nanomaterials were successfully applied to capture glycopeptides from complex samples. 28068756 3 7 theme unbiased 501:508 arg1 affinity 510:517 unbiased affinity 501:517 unbiased affinity 501:517 By taking advantage of their merits, such as large surface area, excellent hydrophilicity and unbiased affinity toward all types of glycopeptides, the Fe3O4@mSiO2-IDA nanomaterials were successfully applied to capture glycopeptides from complex samples. 28068756 5 8 gly glycoproteins 851:863 arg1 glycoproteins 851:863 140 glycoproteins 847:863 140 glycoproteins 847:863 Especially, as a result, 424 glycopeptides assigned to 140 glycoproteins were identified from only 2 μL human serum. 28068756 2 9 theme @ 300:300 arg1 mSiO2-IDA 301:309 Fe3O4@mSiO2-IDA 295:309 Fe3O4@mSiO2-IDA 295:309 In this report, hydrophilic magnetic mesoporous silica materials (denoted as Fe3O4@mSiO2-IDA) were designed and synthesized as an outstanding enrichment platform for glycopeptide analysis. 28068756 3 10 theme large 452:456 arg1 area 466:469 large surface area 452:469 large surface area 452:469 By taking advantage of their merits, such as large surface area, excellent hydrophilicity and unbiased affinity toward all types of glycopeptides, the Fe3O4@mSiO2-IDA nanomaterials were successfully applied to capture glycopeptides from complex samples. 28068756 2 11 theme Fe3O4 295:299 arg1 mSiO2-IDA 301:309 Fe3O4@mSiO2-IDA 295:309 Fe3O4@mSiO2-IDA 295:309 In this report, hydrophilic magnetic mesoporous silica materials (denoted as Fe3O4@mSiO2-IDA) were designed and synthesized as an outstanding enrichment platform for glycopeptide analysis. 28068756 3 12 from samples 652:658 arg1 glycopeptides 625:637 glycopeptides 625:637 glycopeptides from complex samples 625:658 By taking advantage of their merits, such as large surface area, excellent hydrophilicity and unbiased affinity toward all types of glycopeptides, the Fe3O4@mSiO2-IDA nanomaterials were successfully applied to capture glycopeptides from complex samples. 28068756 1 13 theme glycoproteomics 191:205 arg1 profiling 207:215 glycoproteomics profiling 191:215 glycoproteomics profiling 191:215 Hydrophilic interaction liquid chromatography (HILIC) is a significant enrichment strategy in glycoproteomics profiling. 28068756 0 14 theme Mesoporous 12:21 arg1 Silica 23:28 Hydrophilic Mesoporous Silica 0:28 Hydrophilic Mesoporous Silica 0:28 Hydrophilic Mesoporous Silica Materials for Highly Specific Enrichment of N-Linked Glycopeptide. 28068756 3 15 theme glycopeptides 539:551 arg1 types 530:534 all types 526:534 all types of glycopeptides 526:551 By taking advantage of their merits, such as large surface area, excellent hydrophilicity and unbiased affinity toward all types of glycopeptides, the Fe3O4@mSiO2-IDA nanomaterials were successfully applied to capture glycopeptides from complex samples. 28068756 4 16 theme glycopeptides 675:687 arg1 total 663:667 A total 661:667 A total of 25 glycopeptides from horseradish peroxidase (HRP) digests and 33 glycopeptides from IgG 661:759 A total of 25 glycopeptides from horseradish peroxidase (HRP) digests and 33 glycopeptides from IgG were identified, respectively. 28068756 1 17 theme Hydrophilic 97:107 arg1 strategy 179:186 a significant enrichment strategy 154:186 a significant enrichment strategy in glycoproteomics profiling 154:215 Hydrophilic interaction liquid chromatography (HILIC) is a significant enrichment strategy in glycoproteomics profiling. 28068756 1 17 theme Hydrophilic 97:107 arg1 HILIC 144:148 HILIC 144:148 HILIC 144:148 Hydrophilic interaction liquid chromatography (HILIC) is a significant enrichment strategy in glycoproteomics profiling. 28068756 1 17 theme Hydrophilic 97:107 arg1 chromatography 128:141 Hydrophilic interaction liquid chromatography 97:141 Hydrophilic interaction liquid chromatography (HILIC) 97:149 Hydrophilic interaction liquid chromatography (HILIC) is a significant enrichment strategy in glycoproteomics profiling. 28068756 4 18 theme peroxidase 706:715 arg1 digests 723:729 horseradish peroxidase (HRP) digests 694:729 horseradish peroxidase (HRP) digests 694:729 A total of 25 glycopeptides from horseradish peroxidase (HRP) digests and 33 glycopeptides from IgG were identified, respectively. 28068756 0 19 theme Hydrophilic 0:10 arg1 Silica 23:28 Hydrophilic Mesoporous Silica 0:28 Hydrophilic Mesoporous Silica 0:28 Hydrophilic Mesoporous Silica Materials for Highly Specific Enrichment of N-Linked Glycopeptide. 28068756 1 20 theme interaction 109:119 arg1 strategy 179:186 a significant enrichment strategy 154:186 a significant enrichment strategy in glycoproteomics profiling 154:215 Hydrophilic interaction liquid chromatography (HILIC) is a significant enrichment strategy in glycoproteomics profiling. 28068756 1 20 theme interaction 109:119 arg1 HILIC 144:148 HILIC 144:148 HILIC 144:148 Hydrophilic interaction liquid chromatography (HILIC) is a significant enrichment strategy in glycoproteomics profiling. 28068756 1 20 theme interaction 109:119 arg1 chromatography 128:141 Hydrophilic interaction liquid chromatography 97:141 Hydrophilic interaction liquid chromatography (HILIC) 97:149 Hydrophilic interaction liquid chromatography (HILIC) is a significant enrichment strategy in glycoproteomics profiling. 28068756 4 21 theme horseradish 694:704 arg1 HRP 718:720 HRP 718:720 HRP 718:720 A total of 25 glycopeptides from horseradish peroxidase (HRP) digests and 33 glycopeptides from IgG were identified, respectively. 28068756 4 21 theme horseradish 694:704 arg1 peroxidase 706:715 horseradish peroxidase 694:715 horseradish peroxidase (HRP) digests 694:729 A total of 25 glycopeptides from horseradish peroxidase (HRP) digests and 33 glycopeptides from IgG were identified, respectively. 28068756 2 22 gly glycopeptide 384:395 arg2 glycopeptide 384:395 glycopeptide analysis 384:404 glycopeptide analysis 384:404 In this report, hydrophilic magnetic mesoporous silica materials (denoted as Fe3O4@mSiO2-IDA) were designed and synthesized as an outstanding enrichment platform for glycopeptide analysis. 28068756 4 23 from IgG 757:759 arg1 digests 723:729 horseradish peroxidase (HRP) digests 694:729 horseradish peroxidase (HRP) digests 694:729 A total of 25 glycopeptides from horseradish peroxidase (HRP) digests and 33 glycopeptides from IgG were identified, respectively. 28068756 4 23 from IgG 757:759 arg1 glycopeptides 738:750 33 glycopeptides 735:750 33 glycopeptides from IgG 735:759 A total of 25 glycopeptides from horseradish peroxidase (HRP) digests and 33 glycopeptides from IgG were identified, respectively. 28068756 1 24 theme liquid 121:126 arg1 strategy 179:186 a significant enrichment strategy 154:186 a significant enrichment strategy in glycoproteomics profiling 154:215 Hydrophilic interaction liquid chromatography (HILIC) is a significant enrichment strategy in glycoproteomics profiling. 28068756 1 24 theme liquid 121:126 arg1 HILIC 144:148 HILIC 144:148 HILIC 144:148 Hydrophilic interaction liquid chromatography (HILIC) is a significant enrichment strategy in glycoproteomics profiling. 28068756 1 24 theme liquid 121:126 arg1 chromatography 128:141 Hydrophilic interaction liquid chromatography 97:141 Hydrophilic interaction liquid chromatography (HILIC) 97:149 Hydrophilic interaction liquid chromatography (HILIC) is a significant enrichment strategy in glycoproteomics profiling. 28068756 5 25 gly glycopeptides 821:833 arg2 glycopeptides 821:833 424 glycopeptides 817:833 424 glycopeptides assigned to 140 glycoproteins 817:863 Especially, as a result, 424 glycopeptides assigned to 140 glycoproteins were identified from only 2 μL human serum. 28068756 5 25 gly glycopeptides 821:833 arg2 result 809:814 a result 807:814 a result 807:814 Especially, as a result, 424 glycopeptides assigned to 140 glycoproteins were identified from only 2 μL human serum. 28068756 3 26 gly glycopeptides 625:637 arg1 samples 652:658 complex samples 644:658 complex samples 644:658 By taking advantage of their merits, such as large surface area, excellent hydrophilicity and unbiased affinity toward all types of glycopeptides, the Fe3O4@mSiO2-IDA nanomaterials were successfully applied to capture glycopeptides from complex samples. 28068756 3 26 gly glycopeptides 625:637 arg2 glycopeptides 625:637 glycopeptides 625:637 glycopeptides from complex samples 625:658 By taking advantage of their merits, such as large surface area, excellent hydrophilicity and unbiased affinity toward all types of glycopeptides, the Fe3O4@mSiO2-IDA nanomaterials were successfully applied to capture glycopeptides from complex samples. 28068756 5 27 dep serum 902:906 arg1 μL 893:894 μL 893:894 μL 893:894 Especially, as a result, 424 glycopeptides assigned to 140 glycoproteins were identified from only 2 μL human serum. 28068756 4 28 from total 663:667 arg1 digests 723:729 horseradish peroxidase (HRP) digests 694:729 horseradish peroxidase (HRP) digests 694:729 A total of 25 glycopeptides from horseradish peroxidase (HRP) digests and 33 glycopeptides from IgG were identified, respectively. 28068756 4 28 from total 663:667 arg1 glycopeptides 738:750 33 glycopeptides 735:750 33 glycopeptides from IgG 735:759 A total of 25 glycopeptides from horseradish peroxidase (HRP) digests and 33 glycopeptides from IgG were identified, respectively. 28068756 3 29 theme merits 436:441 arg1 advantage 417:425 advantage 417:425 advantage of their merits, such as large surface area, excellent hydrophilicity and unbiased affinity toward all types of glycopeptides 417:551 By taking advantage of their merits, such as large surface area, excellent hydrophilicity and unbiased affinity toward all types of glycopeptides, the Fe3O4@mSiO2-IDA nanomaterials were successfully applied to capture glycopeptides from complex samples. 28068756 4 30 gly glycopeptides 738:750 arg1 IgG 757:759 IgG 757:759 IgG 757:759 A total of 25 glycopeptides from horseradish peroxidase (HRP) digests and 33 glycopeptides from IgG were identified, respectively. 28068756 4 30 gly glycopeptides 738:750 arg2 glycopeptides 738:750 33 glycopeptides 735:750 33 glycopeptides from IgG 735:759 A total of 25 glycopeptides from horseradish peroxidase (HRP) digests and 33 glycopeptides from IgG were identified, respectively. 28068756 2 31 theme silica 266:271 arg1 platform 371:378 an outstanding enrichment platform 345:378 an outstanding enrichment platform for glycopeptide analysis 345:404 In this report, hydrophilic magnetic mesoporous silica materials (denoted as Fe3O4@mSiO2-IDA) were designed and synthesized as an outstanding enrichment platform for glycopeptide analysis. 28068756 2 31 theme silica 266:271 arg1 materials 273:281 hydrophilic magnetic mesoporous silica materials 234:281 hydrophilic magnetic mesoporous silica materials (denoted as Fe3O4@mSiO2-IDA) 234:310 In this report, hydrophilic magnetic mesoporous silica materials (denoted as Fe3O4@mSiO2-IDA) were designed and synthesized as an outstanding enrichment platform for glycopeptide analysis. 28068756 2 32 theme mesoporous 255:264 arg1 platform 371:378 an outstanding enrichment platform 345:378 an outstanding enrichment platform for glycopeptide analysis 345:404 In this report, hydrophilic magnetic mesoporous silica materials (denoted as Fe3O4@mSiO2-IDA) were designed and synthesized as an outstanding enrichment platform for glycopeptide analysis. 28068756 2 32 theme mesoporous 255:264 arg1 materials 273:281 hydrophilic magnetic mesoporous silica materials 234:281 hydrophilic magnetic mesoporous silica materials (denoted as Fe3O4@mSiO2-IDA) 234:310 In this report, hydrophilic magnetic mesoporous silica materials (denoted as Fe3O4@mSiO2-IDA) were designed and synthesized as an outstanding enrichment platform for glycopeptide analysis. 28068756 2 33 theme magnetic 246:253 arg1 platform 371:378 an outstanding enrichment platform 345:378 an outstanding enrichment platform for glycopeptide analysis 345:404 In this report, hydrophilic magnetic mesoporous silica materials (denoted as Fe3O4@mSiO2-IDA) were designed and synthesized as an outstanding enrichment platform for glycopeptide analysis. 28068756 2 33 theme magnetic 246:253 arg1 materials 273:281 hydrophilic magnetic mesoporous silica materials 234:281 hydrophilic magnetic mesoporous silica materials (denoted as Fe3O4@mSiO2-IDA) 234:310 In this report, hydrophilic magnetic mesoporous silica materials (denoted as Fe3O4@mSiO2-IDA) were designed and synthesized as an outstanding enrichment platform for glycopeptide analysis. 28068756 2 34 theme enrichment 360:369 arg1 materials 273:281 hydrophilic magnetic mesoporous silica materials 234:281 hydrophilic magnetic mesoporous silica materials (denoted as Fe3O4@mSiO2-IDA) 234:310 In this report, hydrophilic magnetic mesoporous silica materials (denoted as Fe3O4@mSiO2-IDA) were designed and synthesized as an outstanding enrichment platform for glycopeptide analysis. 28068756 2 34 theme enrichment 360:369 arg1 platform 371:378 an outstanding enrichment platform 345:378 an outstanding enrichment platform for glycopeptide analysis 345:404 In this report, hydrophilic magnetic mesoporous silica materials (denoted as Fe3O4@mSiO2-IDA) were designed and synthesized as an outstanding enrichment platform for glycopeptide analysis. 28068756 0 35 theme Specific 51:58 arg1 Enrichment 60:69 Highly Specific Enrichment 44:69 Highly Specific Enrichment of N-Linked Glycopeptide 44:94 Hydrophilic Mesoporous Silica Materials for Highly Specific Enrichment of N-Linked Glycopeptide. 28068756 2 36 theme hydrophilic 234:244 arg1 platform 371:378 an outstanding enrichment platform 345:378 an outstanding enrichment platform for glycopeptide analysis 345:404 In this report, hydrophilic magnetic mesoporous silica materials (denoted as Fe3O4@mSiO2-IDA) were designed and synthesized as an outstanding enrichment platform for glycopeptide analysis. 28068756 2 36 theme hydrophilic 234:244 arg1 materials 273:281 hydrophilic magnetic mesoporous silica materials 234:281 hydrophilic magnetic mesoporous silica materials (denoted as Fe3O4@mSiO2-IDA) 234:310 In this report, hydrophilic magnetic mesoporous silica materials (denoted as Fe3O4@mSiO2-IDA) were designed and synthesized as an outstanding enrichment platform for glycopeptide analysis. 28068756 2 37 theme outstanding 348:358 arg1 materials 273:281 hydrophilic magnetic mesoporous silica materials 234:281 hydrophilic magnetic mesoporous silica materials (denoted as Fe3O4@mSiO2-IDA) 234:310 In this report, hydrophilic magnetic mesoporous silica materials (denoted as Fe3O4@mSiO2-IDA) were designed and synthesized as an outstanding enrichment platform for glycopeptide analysis. 28068756 2 37 theme outstanding 348:358 arg1 platform 371:378 an outstanding enrichment platform 345:378 an outstanding enrichment platform for glycopeptide analysis 345:404 In this report, hydrophilic magnetic mesoporous silica materials (denoted as Fe3O4@mSiO2-IDA) were designed and synthesized as an outstanding enrichment platform for glycopeptide analysis. 28068756 5 38 dep μL 893:894 arg1 2 891:891 2 891:891 2 891:891 Especially, as a result, 424 glycopeptides assigned to 140 glycoproteins were identified from only 2 μL human serum. 28068756 3 39 theme mSiO2-IDA 564:572 arg1 nanomaterials 574:586 the Fe3O4@mSiO2-IDA nanomaterials 554:586 the Fe3O4@mSiO2-IDA nanomaterials 554:586 By taking advantage of their merits, such as large surface area, excellent hydrophilicity and unbiased affinity toward all types of glycopeptides, the Fe3O4@mSiO2-IDA nanomaterials were successfully applied to capture glycopeptides from complex samples. 28068756 3 40 theme Fe3O4 558:562 arg1 nanomaterials 574:586 the Fe3O4@mSiO2-IDA nanomaterials 554:586 the Fe3O4@mSiO2-IDA nanomaterials 554:586 By taking advantage of their merits, such as large surface area, excellent hydrophilicity and unbiased affinity toward all types of glycopeptides, the Fe3O4@mSiO2-IDA nanomaterials were successfully applied to capture glycopeptides from complex samples. 28068756 1 41 theme significant 156:166 arg1 chromatography 128:141 Hydrophilic interaction liquid chromatography 97:141 Hydrophilic interaction liquid chromatography (HILIC) 97:149 Hydrophilic interaction liquid chromatography (HILIC) is a significant enrichment strategy in glycoproteomics profiling. 28068756 1 41 theme significant 156:166 arg1 strategy 179:186 a significant enrichment strategy 154:186 a significant enrichment strategy in glycoproteomics profiling 154:215 Hydrophilic interaction liquid chromatography (HILIC) is a significant enrichment strategy in glycoproteomics profiling. 28068756 3 42 theme surface 458:464 arg1 area 466:469 large surface area 452:469 large surface area 452:469 By taking advantage of their merits, such as large surface area, excellent hydrophilicity and unbiased affinity toward all types of glycopeptides, the Fe3O4@mSiO2-IDA nanomaterials were successfully applied to capture glycopeptides from complex samples. 28068756 0 43 theme N-Linked 74:81 arg1 Glycopeptide 83:94 N-Linked Glycopeptide 74:94 N-Linked Glycopeptide 74:94 Hydrophilic Mesoporous Silica Materials for Highly Specific Enrichment of N-Linked Glycopeptide. 28068756 3 44 theme excellent 472:480 arg1 hydrophilicity 482:495 excellent hydrophilicity 472:495 excellent hydrophilicity 472:495 By taking advantage of their merits, such as large surface area, excellent hydrophilicity and unbiased affinity toward all types of glycopeptides, the Fe3O4@mSiO2-IDA nanomaterials were successfully applied to capture glycopeptides from complex samples. 28068756 5 45 theme human 896:900 arg1 serum 902:906 only 2 μL human serum 886:906 only 2 μL human serum 886:906 Especially, as a result, 424 glycopeptides assigned to 140 glycoproteins were identified from only 2 μL human serum. 28068756 2 46 dep materials 273:281 arg1 denoted 284:290 denoted 284:290 denoted as Fe3O4@mSiO2-IDA 284:309 In this report, hydrophilic magnetic mesoporous silica materials (denoted as Fe3O4@mSiO2-IDA) were designed and synthesized as an outstanding enrichment platform for glycopeptide analysis. 28068756 3 47 theme complex 644:650 arg1 samples 652:658 complex samples 644:658 complex samples 644:658 By taking advantage of their merits, such as large surface area, excellent hydrophilicity and unbiased affinity toward all types of glycopeptides, the Fe3O4@mSiO2-IDA nanomaterials were successfully applied to capture glycopeptides from complex samples. 28068756 2 48 theme glycopeptide 384:395 arg1 analysis 397:404 glycopeptide analysis 384:404 glycopeptide analysis 384:404 In this report, hydrophilic magnetic mesoporous silica materials (denoted as Fe3O4@mSiO2-IDA) were designed and synthesized as an outstanding enrichment platform for glycopeptide analysis. 28068756 4 49 from digests 723:729 arg1 total 663:667 A total 661:667 A total of 25 glycopeptides from horseradish peroxidase (HRP) digests and 33 glycopeptides from IgG 661:759 A total of 25 glycopeptides from horseradish peroxidase (HRP) digests and 33 glycopeptides from IgG were identified, respectively. 28068756 4 49 from digests 723:729 arg1 glycopeptides 675:687 25 glycopeptides 672:687 25 glycopeptides from horseradish peroxidase (HRP) digests and 33 glycopeptides from IgG 672:759 A total of 25 glycopeptides from horseradish peroxidase (HRP) digests and 33 glycopeptides from IgG were identified, respectively. 27933254 2 0 theme 73.87 U/mg 299:308 arg1 fold 251:254 6.34 fold 246:254 6.34 fold of purification rate, 5.04 % of yield, and 73.87 U/mg of specific activity 246:329 In this study, a hatching enzyme was purified from starfish (Asterina pectinifera) with 6.34 fold of purification rate, 5.04 % of yield, and 73.87 U/mg of specific activity. 27933254 4 1 dep pH 477:478 arg1 The 465:467 The 465:467 The 465:467 The optimal pH and temperature of the hatching enzyme activity were pH 7.0 and 40 °C, respectively, while those of stability were pH 8 and 20 °C. 27933254 1 2 theme egg 153:155 arg1 membrane 141:148 the membrane 137:148 the membrane of egg 137:155 Hatching enzyme is a protease which can degrade the membrane of egg. 27933254 4 3 theme activity 519:526 arg1 temperature 484:494 temperature 484:494 temperature 484:494 The optimal pH and temperature of the hatching enzyme activity were pH 7.0 and 40 °C, respectively, while those of stability were pH 8 and 20 °C. 27933254 4 3 theme activity 519:526 arg1 pH 477:478 optimal pH 469:478 optimal pH 469:478 The optimal pH and temperature of the hatching enzyme activity were pH 7.0 and 40 °C, respectively, while those of stability were pH 8 and 20 °C. 27933254 3 4 theme N-linked 438:445 arg1 oligosaccharides 447:462 N-linked oligosaccharides 438:462 N-linked oligosaccharides 438:462 The molecular weight of starfish hatching enzyme was 86 kDa, which was reduced to 62 kDa after removal of N-linked oligosaccharides. 27933254 9 5 theme starfish 1012:1019 arg1 enzyme 1030:1035 the starfish hatching enzyme 1008:1035 the starfish hatching enzyme 1008:1035 Therefore, the starfish hatching enzyme was classified as a serine-zinc protease. 27933254 9 5 theme starfish 1012:1019 arg1 protease 1069:1076 a serine-zinc protease 1055:1076 a serine-zinc protease 1055:1076 Therefore, the starfish hatching enzyme was classified as a serine-zinc protease. 27933254 0 6 theme enzyme 37:42 arg1 Characterization 0:15 Characterization 0:15 Characterization of a novel hatching enzyme 0:42 Characterization of a novel hatching enzyme purified from starfish Asterina pectinifera. 27933254 9 7 theme hatching 1021:1028 arg1 enzyme 1030:1035 the starfish hatching enzyme 1008:1035 the starfish hatching enzyme 1008:1035 Therefore, the starfish hatching enzyme was classified as a serine-zinc protease. 27933254 9 7 theme hatching 1021:1028 arg1 protease 1069:1076 a serine-zinc protease 1055:1076 a serine-zinc protease 1055:1076 Therefore, the starfish hatching enzyme was classified as a serine-zinc protease. 27933254 7 8 theme enzyme 898:903 arg1 activity 905:912 the enzyme activity 894:912 the enzyme activity 894:912 In addition, Ca2+, Mg2+, and Cu2+ did not affect the enzyme activity. 27933254 1 9 theme Hatching 89:96 arg1 enzyme 98:103 Hatching enzyme 89:103 Hatching enzyme 89:103 Hatching enzyme is a protease which can degrade the membrane of egg. 27933254 1 9 theme Hatching 89:96 arg1 protease 110:117 a protease 108:117 a protease which can degrade the membrane of egg 108:155 Hatching enzyme is a protease which can degrade the membrane of egg. 27933254 8 10 theme starfish 919:926 arg1 activity 944:951 The starfish hatching enzyme activity 915:951 The starfish hatching enzyme activity pretreated with EDTA 915:972 The starfish hatching enzyme activity pretreated with EDTA was recovered by Zn2+. 27933254 3 11 theme enzyme 374:379 arg1 86 kDa 385:390 86 kDa 385:390 86 kDa 385:390 The molecular weight of starfish hatching enzyme was 86 kDa, which was reduced to 62 kDa after removal of N-linked oligosaccharides. 27933254 3 11 theme enzyme 374:379 arg1 weight 346:351 The molecular weight 332:351 The molecular weight of starfish hatching enzyme 332:379 The molecular weight of starfish hatching enzyme was 86 kDa, which was reduced to 62 kDa after removal of N-linked oligosaccharides. 27933254 3 12 theme molecular 336:344 arg1 86 kDa 385:390 86 kDa 385:390 86 kDa 385:390 The molecular weight of starfish hatching enzyme was 86 kDa, which was reduced to 62 kDa after removal of N-linked oligosaccharides. 27933254 3 12 theme molecular 336:344 arg1 weight 346:351 The molecular weight 332:351 The molecular weight of starfish hatching enzyme 332:379 The molecular weight of starfish hatching enzyme was 86 kDa, which was reduced to 62 kDa after removal of N-linked oligosaccharides. 27933254 2 13 theme activity 322:329 arg1 yield 288:292 yield 288:292 yield 288:292 In this study, a hatching enzyme was purified from starfish (Asterina pectinifera) with 6.34 fold of purification rate, 5.04 % of yield, and 73.87 U/mg of specific activity. 27933254 2 13 theme activity 322:329 arg1 rate 272:275 purification rate 259:275 purification rate 259:275 In this study, a hatching enzyme was purified from starfish (Asterina pectinifera) with 6.34 fold of purification rate, 5.04 % of yield, and 73.87 U/mg of specific activity. 27933254 2 13 theme activity 322:329 arg1 % 283:283 5.04 % 278:283 5.04 % of yield 278:292 In this study, a hatching enzyme was purified from starfish (Asterina pectinifera) with 6.34 fold of purification rate, 5.04 % of yield, and 73.87 U/mg of specific activity. 27933254 2 13 theme activity 322:329 arg1 activity 322:329 specific activity 313:329 specific activity 313:329 In this study, a hatching enzyme was purified from starfish (Asterina pectinifera) with 6.34 fold of purification rate, 5.04 % of yield, and 73.87 U/mg of specific activity. 27933254 2 13 theme activity 322:329 arg1 73.87 U/mg 299:308 73.87 U/mg 299:308 73.87 U/mg of specific activity 299:329 In this study, a hatching enzyme was purified from starfish (Asterina pectinifera) with 6.34 fold of purification rate, 5.04 % of yield, and 73.87 U/mg of specific activity. 27933254 0 14 theme novel 22:26 arg1 enzyme 37:42 a novel hatching enzyme 20:42 a novel hatching enzyme 20:42 Characterization of a novel hatching enzyme purified from starfish Asterina pectinifera. 27933254 3 15 link N-linked 438:445 arg1 oligosaccharides 447:462 N-linked oligosaccharides 438:462 N-linked oligosaccharides 438:462 The molecular weight of starfish hatching enzyme was 86 kDa, which was reduced to 62 kDa after removal of N-linked oligosaccharides. 27933254 2 16 theme rate 272:275 arg1 fold 251:254 6.34 fold 246:254 6.34 fold of purification rate, 5.04 % of yield, and 73.87 U/mg of specific activity 246:329 In this study, a hatching enzyme was purified from starfish (Asterina pectinifera) with 6.34 fold of purification rate, 5.04 % of yield, and 73.87 U/mg of specific activity. 27933254 4 17 theme enzyme 512:517 arg1 activity 519:526 the hatching enzyme activity 499:526 the hatching enzyme activity 499:526 The optimal pH and temperature of the hatching enzyme activity were pH 7.0 and 40 °C, respectively, while those of stability were pH 8 and 20 °C. 27933254 2 18 theme purification 259:270 arg1 rate 272:275 purification rate 259:275 purification rate 259:275 In this study, a hatching enzyme was purified from starfish (Asterina pectinifera) with 6.34 fold of purification rate, 5.04 % of yield, and 73.87 U/mg of specific activity. 27933254 3 19 theme starfish 356:363 arg1 enzyme 374:379 starfish hatching enzyme 356:379 starfish hatching enzyme 356:379 The molecular weight of starfish hatching enzyme was 86 kDa, which was reduced to 62 kDa after removal of N-linked oligosaccharides. 27933254 4 20 theme hatching 503:510 arg1 activity 519:526 the hatching enzyme activity 499:526 the hatching enzyme activity 499:526 The optimal pH and temperature of the hatching enzyme activity were pH 7.0 and 40 °C, respectively, while those of stability were pH 8 and 20 °C. 27933254 6 21 theme enzyme 755:760 arg1 activity 762:769 the enzyme activity 751:769 the enzyme activity 751:769 Zn2+ increased the enzyme activity by 167.28 %, while EDTA, TPCK, TGCK, leupeptin, PMSF, and TLCK decreased. 27933254 3 22 theme hatching 365:372 arg1 enzyme 374:379 starfish hatching enzyme 356:379 starfish hatching enzyme 356:379 The molecular weight of starfish hatching enzyme was 86 kDa, which was reduced to 62 kDa after removal of N-linked oligosaccharides. 27933254 0 23 theme hatching 28:35 arg1 enzyme 37:42 a novel hatching enzyme 20:42 a novel hatching enzyme 20:42 Characterization of a novel hatching enzyme purified from starfish Asterina pectinifera. 27933254 9 24 theme serine-zinc 1057:1067 arg1 enzyme 1030:1035 the starfish hatching enzyme 1008:1035 the starfish hatching enzyme 1008:1035 Therefore, the starfish hatching enzyme was classified as a serine-zinc protease. 27933254 9 24 theme serine-zinc 1057:1067 arg1 protease 1069:1076 a serine-zinc protease 1055:1076 a serine-zinc protease 1055:1076 Therefore, the starfish hatching enzyme was classified as a serine-zinc protease. 27933254 4 25 theme optimal 469:475 arg1 pH 477:478 optimal pH 469:478 optimal pH 469:478 The optimal pH and temperature of the hatching enzyme activity were pH 7.0 and 40 °C, respectively, while those of stability were pH 8 and 20 °C. 27933254 8 26 theme hatching 928:935 arg1 activity 944:951 The starfish hatching enzyme activity 915:951 The starfish hatching enzyme activity pretreated with EDTA 915:972 The starfish hatching enzyme activity pretreated with EDTA was recovered by Zn2+. 27933254 5 27 theme K/K 649:651 arg1 parameters 623:632 The kinetic parameters 611:632 The kinetic parameters 611:632 The kinetic parameters, V , K , K and K/K values were 0.197 U/ml, 0.289 mg/ml, 112.57 s-1, and 389.52 ml/mg s, respectively. 27933254 5 27 theme K/K 649:651 arg1 values 653:658 K/K values 649:658 K/K values 649:658 The kinetic parameters, V , K , K and K/K values were 0.197 U/ml, 0.289 mg/ml, 112.57 s-1, and 389.52 ml/mg s, respectively. 27933254 5 28 theme kinetic 615:621 arg1 parameters 623:632 The kinetic parameters 611:632 The kinetic parameters 611:632 The kinetic parameters, V , K , K and K/K values were 0.197 U/ml, 0.289 mg/ml, 112.57 s-1, and 389.52 ml/mg s, respectively. 27933254 5 28 theme kinetic 615:621 arg1 V 635:635 V 635:635 V 635:635 The kinetic parameters, V , K , K and K/K values were 0.197 U/ml, 0.289 mg/ml, 112.57 s-1, and 389.52 ml/mg s, respectively. 27933254 5 28 theme kinetic 615:621 arg1 values 653:658 K/K values 649:658 K/K values 649:658 The kinetic parameters, V , K , K and K/K values were 0.197 U/ml, 0.289 mg/ml, 112.57 s-1, and 389.52 ml/mg s, respectively. 27933254 5 28 theme kinetic 615:621 arg1 K 639:639 K 639:639 K 639:639 The kinetic parameters, V , K , K and K/K values were 0.197 U/ml, 0.289 mg/ml, 112.57 s-1, and 389.52 ml/mg s, respectively. 27933254 5 28 theme kinetic 615:621 arg1 0.197 U/ml 665:674 0.197 U/ml 665:674 0.197 U/ml 665:674 The kinetic parameters, V , K , K and K/K values were 0.197 U/ml, 0.289 mg/ml, 112.57 s-1, and 389.52 ml/mg s, respectively. 27933254 5 28 theme kinetic 615:621 arg1 K 643:643 K 643:643 K 643:643 The kinetic parameters, V , K , K and K/K values were 0.197 U/ml, 0.289 mg/ml, 112.57 s-1, and 389.52 ml/mg s, respectively. 27933254 3 29 theme oligosaccharides 447:462 arg1 removal 427:433 removal 427:433 removal of N-linked oligosaccharides 427:462 The molecular weight of starfish hatching enzyme was 86 kDa, which was reduced to 62 kDa after removal of N-linked oligosaccharides. 27933254 2 30 theme yield 288:292 arg1 yield 288:292 yield 288:292 yield 288:292 In this study, a hatching enzyme was purified from starfish (Asterina pectinifera) with 6.34 fold of purification rate, 5.04 % of yield, and 73.87 U/mg of specific activity. 27933254 2 30 theme yield 288:292 arg1 rate 272:275 purification rate 259:275 purification rate 259:275 In this study, a hatching enzyme was purified from starfish (Asterina pectinifera) with 6.34 fold of purification rate, 5.04 % of yield, and 73.87 U/mg of specific activity. 27933254 2 30 theme yield 288:292 arg1 % 283:283 5.04 % 278:283 5.04 % of yield 278:292 In this study, a hatching enzyme was purified from starfish (Asterina pectinifera) with 6.34 fold of purification rate, 5.04 % of yield, and 73.87 U/mg of specific activity. 27933254 2 30 theme yield 288:292 arg1 activity 322:329 specific activity 313:329 specific activity 313:329 In this study, a hatching enzyme was purified from starfish (Asterina pectinifera) with 6.34 fold of purification rate, 5.04 % of yield, and 73.87 U/mg of specific activity. 27933254 2 30 theme yield 288:292 arg1 73.87 U/mg 299:308 73.87 U/mg 299:308 73.87 U/mg of specific activity 299:329 In this study, a hatching enzyme was purified from starfish (Asterina pectinifera) with 6.34 fold of purification rate, 5.04 % of yield, and 73.87 U/mg of specific activity. 27933254 2 31 theme hatching 175:182 arg1 enzyme 184:189 a hatching enzyme 173:189 a hatching enzyme 173:189 In this study, a hatching enzyme was purified from starfish (Asterina pectinifera) with 6.34 fold of purification rate, 5.04 % of yield, and 73.87 U/mg of specific activity. 27933254 8 32 theme enzyme 937:942 arg1 activity 944:951 The starfish hatching enzyme activity 915:951 The starfish hatching enzyme activity pretreated with EDTA 915:972 The starfish hatching enzyme activity pretreated with EDTA was recovered by Zn2+. 27933254 2 33 theme % 283:283 arg1 fold 251:254 6.34 fold 246:254 6.34 fold of purification rate, 5.04 % of yield, and 73.87 U/mg of specific activity 246:329 In this study, a hatching enzyme was purified from starfish (Asterina pectinifera) with 6.34 fold of purification rate, 5.04 % of yield, and 73.87 U/mg of specific activity. 27933254 0 34 theme Asterina 67:74 arg1 pectinifera 76:86 starfish Asterina pectinifera 58:86 starfish Asterina pectinifera 58:86 Characterization of a novel hatching enzyme purified from starfish Asterina pectinifera. 27933254 2 35 theme Asterina 219:226 arg1 starfish 209:216 starfish 209:216 starfish (Asterina pectinifera) 209:239 In this study, a hatching enzyme was purified from starfish (Asterina pectinifera) with 6.34 fold of purification rate, 5.04 % of yield, and 73.87 U/mg of specific activity. 27933254 2 35 theme Asterina 219:226 arg1 pectinifera 228:238 Asterina pectinifera 219:238 Asterina pectinifera 219:238 In this study, a hatching enzyme was purified from starfish (Asterina pectinifera) with 6.34 fold of purification rate, 5.04 % of yield, and 73.87 U/mg of specific activity. 27933254 2 36 theme specific 313:320 arg1 activity 322:329 specific activity 313:329 specific activity 313:329 In this study, a hatching enzyme was purified from starfish (Asterina pectinifera) with 6.34 fold of purification rate, 5.04 % of yield, and 73.87 U/mg of specific activity. 27933254 0 37 theme starfish 58:65 arg1 pectinifera 76:86 starfish Asterina pectinifera 58:86 starfish Asterina pectinifera 58:86 Characterization of a novel hatching enzyme purified from starfish Asterina pectinifera. 27490243 0 0 theme pyrophosphate 102:114 arg1 carrier 116:122 a short dolichol pyrophosphate carrier 85:122 a short dolichol pyrophosphate carrier 85:122 N-glycosylation in the thermoacidophilic archaeon Sulfolobus acidocaldarius involves a short dolichol pyrophosphate carrier. 27490243 4 1 theme dolichol 590:597 arg1 pyrophosphate 599:611 a dolichol pyrophosphate 588:611 a dolichol pyrophosphate bearing the intact hexasaccharide, as well as its biosynthetic intermediates 588:688 Here, we used a specialized protocol for extracting lipid-linked oligosaccharides to detect a dolichol pyrophosphate bearing the intact hexasaccharide, as well as its biosynthetic intermediates. 27490243 3 2 dep S. 452:453 arg1 acidocaldarius 455:468 acidocaldarius 455:468 acidocaldarius 455:468 Previously, hexose-bearing dolichol phosphate was detected in a S. acidocaldarius Bligh-Dyer lipid extract. 27490243 0 3 theme dolichol 93:100 arg1 carrier 116:122 a short dolichol pyrophosphate carrier 85:122 a short dolichol pyrophosphate carrier 85:122 N-glycosylation in the thermoacidophilic archaeon Sulfolobus acidocaldarius involves a short dolichol pyrophosphate carrier. 27490243 3 4 located detected 438:445 arg2 phosphate 424:432 hexose-bearing dolichol phosphate 400:432 hexose-bearing dolichol phosphate 400:432 Previously, hexose-bearing dolichol phosphate was detected in a S. acidocaldarius Bligh-Dyer lipid extract. 27490243 3 4 located detected 438:445 arg1 extract 487:493 a S. acidocaldarius Bligh-Dyer lipid extract 450:493 a S. acidocaldarius Bligh-Dyer lipid extract 450:493 Previously, hexose-bearing dolichol phosphate was detected in a S. acidocaldarius Bligh-Dyer lipid extract. 27490243 2 5 link N-linked 301:308 arg1 reminiscent 337:347 an N-linked tribranched hexasaccharide reminiscent 298:347 an N-linked tribranched hexasaccharide reminiscent of the N-glycans assembled in Eukarya 298:385 In the thermoacidophilic archaea Sulfolobus acidocaldarius, glycoproteins are modified by an N-linked tribranched hexasaccharide reminiscent of the N-glycans assembled in Eukarya. 27490243 0 6 from N-glycosylation 0:14 arg1 archaeon 41:48 the thermoacidophilic archaeon 19:48 the thermoacidophilic archaeon Sulfolobus acidocaldarius 19:74 N-glycosylation in the thermoacidophilic archaeon Sulfolobus acidocaldarius involves a short dolichol pyrophosphate carrier. 27490243 5 7 theme same 774:777 arg1 hexasaccharide 779:792 the same hexasaccharide 770:792 the same hexasaccharide 770:792 Furthermore, evidence for N-glycosylation of two S. acidocaldarius proteins by the same hexasaccharide and its derivatives was collected. 27490243 2 8 theme N-glycans 356:364 arg1 reminiscent 337:347 an N-linked tribranched hexasaccharide reminiscent 298:347 an N-linked tribranched hexasaccharide reminiscent of the N-glycans assembled in Eukarya 298:385 In the thermoacidophilic archaea Sulfolobus acidocaldarius, glycoproteins are modified by an N-linked tribranched hexasaccharide reminiscent of the N-glycans assembled in Eukarya. 27490243 4 9 used used 505:508 arg2 we 502:503 we 502:503 we 502:503 Here, we used a specialized protocol for extracting lipid-linked oligosaccharides to detect a dolichol pyrophosphate bearing the intact hexasaccharide, as well as its biosynthetic intermediates. 27490243 5 10 theme S. 740:741 arg1 proteins 758:765 two S. acidocaldarius proteins 736:765 two S. acidocaldarius proteins 736:765 Furthermore, evidence for N-glycosylation of two S. acidocaldarius proteins by the same hexasaccharide and its derivatives was collected. 27490243 3 11 theme Bligh-Dyer 470:479 arg1 extract 487:493 a S. acidocaldarius Bligh-Dyer lipid extract 450:493 a S. acidocaldarius Bligh-Dyer lipid extract 450:493 Previously, hexose-bearing dolichol phosphate was detected in a S. acidocaldarius Bligh-Dyer lipid extract. 27490243 3 12 theme hexose-bearing 400:413 arg1 phosphate 424:432 hexose-bearing dolichol phosphate 400:432 hexose-bearing dolichol phosphate 400:432 Previously, hexose-bearing dolichol phosphate was detected in a S. acidocaldarius Bligh-Dyer lipid extract. 27490243 5 13 theme acidocaldarius 743:756 arg1 proteins 758:765 two S. acidocaldarius proteins 736:765 two S. acidocaldarius proteins 736:765 Furthermore, evidence for N-glycosylation of two S. acidocaldarius proteins by the same hexasaccharide and its derivatives was collected. 27490243 0 14 theme short 87:91 arg1 carrier 116:122 a short dolichol pyrophosphate carrier 85:122 a short dolichol pyrophosphate carrier 85:122 N-glycosylation in the thermoacidophilic archaeon Sulfolobus acidocaldarius involves a short dolichol pyrophosphate carrier. 27490243 3 15 theme lipid 481:485 arg1 extract 487:493 a S. acidocaldarius Bligh-Dyer lipid extract 450:493 a S. acidocaldarius Bligh-Dyer lipid extract 450:493 Previously, hexose-bearing dolichol phosphate was detected in a S. acidocaldarius Bligh-Dyer lipid extract. 27490243 5 16 theme proteins 758:765 arg1 derivatives 802:812 its derivatives 798:812 its derivatives 798:812 Furthermore, evidence for N-glycosylation of two S. acidocaldarius proteins by the same hexasaccharide and its derivatives was collected. 27490243 5 16 theme proteins 758:765 arg1 N-glycosylation 717:731 N-glycosylation 717:731 N-glycosylation of two S. acidocaldarius proteins by the same hexasaccharide 717:792 Furthermore, evidence for N-glycosylation of two S. acidocaldarius proteins by the same hexasaccharide and its derivatives was collected. 27490243 3 17 theme S. 452:453 arg1 extract 487:493 a S. acidocaldarius Bligh-Dyer lipid extract 450:493 a S. acidocaldarius Bligh-Dyer lipid extract 450:493 Previously, hexose-bearing dolichol phosphate was detected in a S. acidocaldarius Bligh-Dyer lipid extract. 27490243 4 18 theme biosynthetic 663:674 arg1 intermediates 676:688 its biosynthetic intermediates 659:688 its biosynthetic intermediates 659:688 Here, we used a specialized protocol for extracting lipid-linked oligosaccharides to detect a dolichol pyrophosphate bearing the intact hexasaccharide, as well as its biosynthetic intermediates. 27490243 2 19 theme archaea 233:239 arg1 acidocaldarius 252:265 the thermoacidophilic archaea Sulfolobus acidocaldarius 211:265 the thermoacidophilic archaea Sulfolobus acidocaldarius 211:265 In the thermoacidophilic archaea Sulfolobus acidocaldarius, glycoproteins are modified by an N-linked tribranched hexasaccharide reminiscent of the N-glycans assembled in Eukarya. 27490243 2 20 theme thermoacidophilic 215:231 arg1 acidocaldarius 252:265 the thermoacidophilic archaea Sulfolobus acidocaldarius 211:265 the thermoacidophilic archaea Sulfolobus acidocaldarius 211:265 In the thermoacidophilic archaea Sulfolobus acidocaldarius, glycoproteins are modified by an N-linked tribranched hexasaccharide reminiscent of the N-glycans assembled in Eukarya. 27490243 0 21 gly N-glycosylation 0:14 arg1 archaeon 41:48 the thermoacidophilic archaeon 19:48 the thermoacidophilic archaeon Sulfolobus acidocaldarius 19:74 N-glycosylation in the thermoacidophilic archaeon Sulfolobus acidocaldarius involves a short dolichol pyrophosphate carrier. 27490243 4 22 theme lipid-linked 548:559 arg1 oligosaccharides 561:576 lipid-linked oligosaccharides 548:576 lipid-linked oligosaccharides 548:576 Here, we used a specialized protocol for extracting lipid-linked oligosaccharides to detect a dolichol pyrophosphate bearing the intact hexasaccharide, as well as its biosynthetic intermediates. 27490243 0 23 theme thermoacidophilic 23:39 arg1 archaeon 41:48 the thermoacidophilic archaeon 19:48 the thermoacidophilic archaeon Sulfolobus acidocaldarius 19:74 N-glycosylation in the thermoacidophilic archaeon Sulfolobus acidocaldarius involves a short dolichol pyrophosphate carrier. 27490243 4 24 theme intact 625:630 arg1 hexasaccharide 632:645 the intact hexasaccharide 621:645 the intact hexasaccharide 621:645 Here, we used a specialized protocol for extracting lipid-linked oligosaccharides to detect a dolichol pyrophosphate bearing the intact hexasaccharide, as well as its biosynthetic intermediates. 27490243 2 25 mod modified 286:293 arg3 reminiscent 337:347 an N-linked tribranched hexasaccharide reminiscent 298:347 an N-linked tribranched hexasaccharide reminiscent of the N-glycans assembled in Eukarya 298:385 In the thermoacidophilic archaea Sulfolobus acidocaldarius, glycoproteins are modified by an N-linked tribranched hexasaccharide reminiscent of the N-glycans assembled in Eukarya. 27490243 2 25 mod modified 286:293 arg1 glycoproteins 268:280 glycoproteins 268:280 glycoproteins 268:280 In the thermoacidophilic archaea Sulfolobus acidocaldarius, glycoproteins are modified by an N-linked tribranched hexasaccharide reminiscent of the N-glycans assembled in Eukarya. 27490243 6 26 theme archaeal 876:883 arg1 N-glycosylation 885:899 archaeal N-glycosylation 876:899 archaeal N-glycosylation 876:899 These findings thus provide novel insight into archaeal N-glycosylation. 27490243 1 27 theme post-translational 146:163 arg1 modification 165:176 a post-translational modification 144:176 a post-translational modification that occurs across evolution 144:205 N-glycosylation is a post-translational modification that occurs across evolution. 27490243 1 27 theme post-translational 146:163 arg1 N-glycosylation 125:139 N-glycosylation 125:139 N-glycosylation 125:139 N-glycosylation is a post-translational modification that occurs across evolution. 27490243 2 28 gly glycoproteins 268:280 arg1 glycoproteins 268:280 glycoproteins 268:280 glycoproteins 268:280 In the thermoacidophilic archaea Sulfolobus acidocaldarius, glycoproteins are modified by an N-linked tribranched hexasaccharide reminiscent of the N-glycans assembled in Eukarya. 27490243 4 29 link lipid-linked 548:559 arg1 oligosaccharides 561:576 lipid-linked oligosaccharides 548:576 lipid-linked oligosaccharides 548:576 Here, we used a specialized protocol for extracting lipid-linked oligosaccharides to detect a dolichol pyrophosphate bearing the intact hexasaccharide, as well as its biosynthetic intermediates. 27490243 4 30 theme specialized 512:522 arg1 protocol 524:531 a specialized protocol 510:531 a specialized protocol for extracting lipid-linked oligosaccharides to detect a dolichol pyrophosphate bearing the intact hexasaccharide, as well as its biosynthetic intermediates 510:688 Here, we used a specialized protocol for extracting lipid-linked oligosaccharides to detect a dolichol pyrophosphate bearing the intact hexasaccharide, as well as its biosynthetic intermediates. 27490243 2 31 theme hexasaccharide 322:335 arg1 reminiscent 337:347 an N-linked tribranched hexasaccharide reminiscent 298:347 an N-linked tribranched hexasaccharide reminiscent of the N-glycans assembled in Eukarya 298:385 In the thermoacidophilic archaea Sulfolobus acidocaldarius, glycoproteins are modified by an N-linked tribranched hexasaccharide reminiscent of the N-glycans assembled in Eukarya. 27490243 3 32 theme dolichol 415:422 arg1 phosphate 424:432 hexose-bearing dolichol phosphate 400:432 hexose-bearing dolichol phosphate 400:432 Previously, hexose-bearing dolichol phosphate was detected in a S. acidocaldarius Bligh-Dyer lipid extract. 27490243 2 33 theme Sulfolobus 241:250 arg1 acidocaldarius 252:265 the thermoacidophilic archaea Sulfolobus acidocaldarius 211:265 the thermoacidophilic archaea Sulfolobus acidocaldarius 211:265 In the thermoacidophilic archaea Sulfolobus acidocaldarius, glycoproteins are modified by an N-linked tribranched hexasaccharide reminiscent of the N-glycans assembled in Eukarya. 27490243 2 34 theme tribranched 310:320 arg1 reminiscent 337:347 an N-linked tribranched hexasaccharide reminiscent 298:347 an N-linked tribranched hexasaccharide reminiscent of the N-glycans assembled in Eukarya 298:385 In the thermoacidophilic archaea Sulfolobus acidocaldarius, glycoproteins are modified by an N-linked tribranched hexasaccharide reminiscent of the N-glycans assembled in Eukarya. 27490243 6 35 theme novel 857:861 arg1 insight 863:869 novel insight 857:869 novel insight into archaeal N-glycosylation 857:899 These findings thus provide novel insight into archaeal N-glycosylation. 27490243 2 36 theme N-linked 301:308 arg1 reminiscent 337:347 an N-linked tribranched hexasaccharide reminiscent 298:347 an N-linked tribranched hexasaccharide reminiscent of the N-glycans assembled in Eukarya 298:385 In the thermoacidophilic archaea Sulfolobus acidocaldarius, glycoproteins are modified by an N-linked tribranched hexasaccharide reminiscent of the N-glycans assembled in Eukarya. 27490243 5 37 gly N-glycosylation 717:731 arg1 proteins 758:765 two S. acidocaldarius proteins 736:765 two S. acidocaldarius proteins 736:765 Furthermore, evidence for N-glycosylation of two S. acidocaldarius proteins by the same hexasaccharide and its derivatives was collected. 26987003 2 0 theme proteins 108:115 arg1 N-glycosylation 89:103 N-glycosylation 89:103 N-glycosylation of proteins 89:115 N-glycosylation of proteins is one of the most important post-translational modifications that occur in various organisms, and is of utmost importance for protein function, stability, secretion, and loca-lization. 26987003 5 1 theme bioinformatic 629:641 arg1 approaches 659:668 bioinformatic and biochemical approaches 629:668 bioinformatic and biochemical approaches 629:668 (Rhodophyta) using bioinformatic and biochemical approaches. 26987003 7 2 theme organisms 971:979 arg1 range 962:966 an evolutionarily vast range 939:966 an evolutionarily vast range of organisms 939:979 Phylogenetic analysis revealed its wide distribution across an evolutionarily vast range of organisms; while the α subunit is highly conserved and its phylogenic tree is similar to the taxon evolutionary tree, the β subunit is less conserved and its pattern somewhat differs from the taxon tree. 26987003 8 3 theme biochemical 1274:1284 arg1 characterization 1286:1301 functional and biochemical characterization 1259:1301 characterization 1286:1301 In addition, the activity of the red microalgal GANAB enzyme was studied, including functional and biochemical characterization using a bioassay, indicating that the enzyme is similar to other eukaryotes ortholog GANAB enzymes. 26987003 10 4 theme biosynthesis 1658:1669 arg1 pathways 1671:1678 the N-glycosylation and polysaccharide biosynthesis pathways 1619:1678 pathways 1671:1678 This study represents a valuable contribution toward understanding the N-glycosylation and polysaccharide biosynthesis pathways in red microalgae. 26987003 7 5 theme β 1093:1093 arg1 subunit 1095:1101 the β subunit 1089:1101 the β subunit 1089:1101 Phylogenetic analysis revealed its wide distribution across an evolutionarily vast range of organisms; while the α subunit is highly conserved and its phylogenic tree is similar to the taxon evolutionary tree, the β subunit is less conserved and its pattern somewhat differs from the taxon tree. 26987003 7 6 theme vast 957:960 arg1 range 962:966 an evolutionarily vast range 939:966 an evolutionarily vast range of organisms 939:979 Phylogenetic analysis revealed its wide distribution across an evolutionarily vast range of organisms; while the α subunit is highly conserved and its phylogenic tree is similar to the taxon evolutionary tree, the β subunit is less conserved and its pattern somewhat differs from the taxon tree. 26987003 6 7 theme consistent 823:832 arg1 motifs 816:821 similar motifs 808:821 similar motifs consistent with that of homolog eukaryotes GANAB genes 808:876 The GANAB-gene was found to be highly conserved evolutionarily (compo-sed of all the common features of α and β subunits) and to exhibit similar motifs consistent with that of homolog eukaryotes GANAB genes. 26987003 6 8 theme α 775:775 arg1 subunits 783:790 α and β subunits 775:790 α and β subunits 775:790 The GANAB-gene was found to be highly conserved evolutionarily (compo-sed of all the common features of α and β subunits) and to exhibit similar motifs consistent with that of homolog eukaryotes GANAB genes. 26987003 5 9 theme biochemical 647:657 arg1 approaches 659:668 bioinformatic and biochemical approaches 629:668 bioinformatic and biochemical approaches 629:668 (Rhodophyta) using bioinformatic and biochemical approaches. 26987003 10 10 gly N-glycosylation 1623:1637 arg1 microalgae 1687:1696 red microalgae 1683:1696 red microalgae 1683:1696 This study represents a valuable contribution toward understanding the N-glycosylation and polysaccharide biosynthesis pathways in red microalgae. 26987003 8 11 theme ortholog 1379:1386 arg1 enzymes 1394:1400 similar to other eukaryotes ortholog GANAB enzymes 1351:1400 similar to other eukaryotes ortholog GANAB enzymes 1351:1400 In addition, the activity of the red microalgal GANAB enzyme was studied, including functional and biochemical characterization using a bioassay, indicating that the enzyme is similar to other eukaryotes ortholog GANAB enzymes. 26987003 8 11 theme ortholog 1379:1386 arg1 enzyme 1341:1346 the enzyme 1337:1346 the enzyme 1337:1346 In addition, the activity of the red microalgal GANAB enzyme was studied, including functional and biochemical characterization using a bioassay, indicating that the enzyme is similar to other eukaryotes ortholog GANAB enzymes. 26987003 4 12 theme marine 576:581 arg1 sp 606:607 a red marine microalga Porphyridium sp 570:607 a red marine microalga Porphyridium sp 570:607 We studied the α 1,3-glucosidase glucosidase II (GANAB) glycoenzyme in a red marine microalga Porphyridium sp. 26987003 3 13 theme proteins 350:357 arg1 pathway 339:345 the N-linked glycosylation pathway 312:345 the N-linked glycosylation pathway of proteins 312:357 Although the N-linked glycosylation pathway of proteins has been extensively characterized in mammals and plants, not much information is available regarding the N-glycosylation pathway in algae. 26987003 6 14 theme subunits 783:790 arg1 features 763:770 all the common features 748:770 all the common features of α and β subunits 748:790 The GANAB-gene was found to be highly conserved evolutionarily (compo-sed of all the common features of α and β subunits) and to exhibit similar motifs consistent with that of homolog eukaryotes GANAB genes. 26987003 4 15 theme red 572:574 arg1 sp 606:607 a red marine microalga Porphyridium sp 570:607 a red marine microalga Porphyridium sp 570:607 We studied the α 1,3-glucosidase glucosidase II (GANAB) glycoenzyme in a red marine microalga Porphyridium sp. 26987003 3 16 theme glycosylation 325:337 arg1 pathway 339:345 the N-linked glycosylation pathway 312:345 the N-linked glycosylation pathway of proteins 312:357 Although the N-linked glycosylation pathway of proteins has been extensively characterized in mammals and plants, not much information is available regarding the N-glycosylation pathway in algae. 26987003 6 17 theme GANAB 866:870 arg1 genes 872:876 homolog eukaryotes GANAB genes 847:876 homolog eukaryotes GANAB genes 847:876 The GANAB-gene was found to be highly conserved evolutionarily (compo-sed of all the common features of α and β subunits) and to exhibit similar motifs consistent with that of homolog eukaryotes GANAB genes. 26987003 7 18 theme taxon 1064:1068 arg1 tree 1083:1086 the taxon evolutionary tree 1060:1086 the taxon evolutionary tree 1060:1086 Phylogenetic analysis revealed its wide distribution across an evolutionarily vast range of organisms; while the α subunit is highly conserved and its phylogenic tree is similar to the taxon evolutionary tree, the β subunit is less conserved and its pattern somewhat differs from the taxon tree. 26987003 6 19 theme β 781:781 arg1 subunits 783:790 α and β subunits 775:790 α and β subunits 775:790 The GANAB-gene was found to be highly conserved evolutionarily (compo-sed of all the common features of α and β subunits) and to exhibit similar motifs consistent with that of homolog eukaryotes GANAB genes. 26987003 10 20 theme polysaccharide 1643:1656 arg1 pathways 1671:1678 the N-glycosylation and polysaccharide biosynthesis pathways 1619:1678 pathways 1671:1678 This study represents a valuable contribution toward understanding the N-glycosylation and polysaccharide biosynthesis pathways in red microalgae. 26987003 3 21 theme much 421:424 arg1 information 426:436 not much information 417:436 not much information 417:436 Although the N-linked glycosylation pathway of proteins has been extensively characterized in mammals and plants, not much information is available regarding the N-glycosylation pathway in algae. 26987003 6 22 theme eukaryotes 855:864 arg1 genes 872:876 homolog eukaryotes GANAB genes 847:876 homolog eukaryotes GANAB genes 847:876 The GANAB-gene was found to be highly conserved evolutionarily (compo-sed of all the common features of α and β subunits) and to exhibit similar motifs consistent with that of homolog eukaryotes GANAB genes. 26987003 7 23 theme evolutionary 1070:1081 arg1 tree 1083:1086 the taxon evolutionary tree 1060:1086 the taxon evolutionary tree 1060:1086 Phylogenetic analysis revealed its wide distribution across an evolutionarily vast range of organisms; while the α subunit is highly conserved and its phylogenic tree is similar to the taxon evolutionary tree, the β subunit is less conserved and its pattern somewhat differs from the taxon tree. 26987003 6 24 with consistent 823:832 arg1 that 839:842 that 839:842 that 839:842 The GANAB-gene was found to be highly conserved evolutionarily (compo-sed of all the common features of α and β subunits) and to exhibit similar motifs consistent with that of homolog eukaryotes GANAB genes. 26987003 4 25 from glycoenzyme 555:565 arg1 sp 606:607 a red marine microalga Porphyridium sp 570:607 a red marine microalga Porphyridium sp 570:607 We studied the α 1,3-glucosidase glucosidase II (GANAB) glycoenzyme in a red marine microalga Porphyridium sp. 26987003 6 26 theme homolog 847:853 arg1 genes 872:876 homolog eukaryotes GANAB genes 847:876 homolog eukaryotes GANAB genes 847:876 The GANAB-gene was found to be highly conserved evolutionarily (compo-sed of all the common features of α and β subunits) and to exhibit similar motifs consistent with that of homolog eukaryotes GANAB genes. 26987003 3 27 from pathway 481:487 arg1 algae 492:496 algae 492:496 algae 492:496 Although the N-linked glycosylation pathway of proteins has been extensively characterized in mammals and plants, not much information is available regarding the N-glycosylation pathway in algae. 26987003 9 28 theme polysaccharide 1425:1438 arg1 production 1440:1449 polysaccharide production 1425:1449 polysaccharide production 1425:1449 A correlation between polysaccharide production and GANAB activity, indicating its involvement in polysaccharide biosynthesis, is also demonstrated. 26987003 10 29 theme valuable 1576:1583 arg1 contribution 1585:1596 a valuable contribution 1574:1596 a valuable contribution toward understanding the N-glycosylation and polysaccharide biosynthesis pathways in red microalgae 1574:1696 This study represents a valuable contribution toward understanding the N-glycosylation and polysaccharide biosynthesis pathways in red microalgae. 26987003 4 30 theme GANAB 548:552 arg1 glycoenzyme 555:565 the α 1,3-glucosidase glucosidase II (GANAB) glycoenzyme 510:565 the α 1,3-glucosidase glucosidase II (GANAB) glycoenzyme in a red marine microalga Porphyridium sp 510:607 We studied the α 1,3-glucosidase glucosidase II (GANAB) glycoenzyme in a red marine microalga Porphyridium sp. 26987003 7 31 theme wide 914:917 arg1 distribution 919:930 its wide distribution 910:930 its wide distribution across an evolutionarily vast range of organisms 910:979 Phylogenetic analysis revealed its wide distribution across an evolutionarily vast range of organisms; while the α subunit is highly conserved and its phylogenic tree is similar to the taxon evolutionary tree, the β subunit is less conserved and its pattern somewhat differs from the taxon tree. 26987003 2 32 theme modifications 165:177 arg1 modifications 165:177 the most important post-translational modifications 127:177 the most important post-translational modifications that occur in various organisms 127:209 N-glycosylation of proteins is one of the most important post-translational modifications that occur in various organisms, and is of utmost importance for protein function, stability, secretion, and loca-lization. 26987003 2 32 theme modifications 165:177 arg1 one 120:122 one 120:122 one 120:122 N-glycosylation of proteins is one of the most important post-translational modifications that occur in various organisms, and is of utmost importance for protein function, stability, secretion, and loca-lization. 26987003 6 33 theme features 763:770 arg1 compo-sed 735:743 compo-sed 735:743 compo-sed 735:743 The GANAB-gene was found to be highly conserved evolutionarily (compo-sed of all the common features of α and β subunits) and to exhibit similar motifs consistent with that of homolog eukaryotes GANAB genes. 26987003 8 34 theme red 1208:1210 arg1 enzyme 1229:1234 the red microalgal GANAB enzyme 1204:1234 the red microalgal GANAB enzyme 1204:1234 In addition, the activity of the red microalgal GANAB enzyme was studied, including functional and biochemical characterization using a bioassay, indicating that the enzyme is similar to other eukaryotes ortholog GANAB enzymes. 26987003 3 35 theme N-linked 316:323 arg1 pathway 339:345 the N-linked glycosylation pathway 312:345 the N-linked glycosylation pathway of proteins 312:357 Although the N-linked glycosylation pathway of proteins has been extensively characterized in mammals and plants, not much information is available regarding the N-glycosylation pathway in algae. 26987003 3 36 link N-linked 316:323 arg1 pathway 339:345 the N-linked glycosylation pathway 312:345 the N-linked glycosylation pathway of proteins 312:357 Although the N-linked glycosylation pathway of proteins has been extensively characterized in mammals and plants, not much information is available regarding the N-glycosylation pathway in algae. 26987003 2 37 gly N-glycosylation 89:103 arg1 proteins 108:115 proteins 108:115 proteins 108:115 N-glycosylation of proteins is one of the most important post-translational modifications that occur in various organisms, and is of utmost importance for protein function, stability, secretion, and loca-lization. 26987003 8 38 theme functional 1259:1268 arg1 characterization 1286:1301 functional and biochemical characterization 1259:1301 characterization 1286:1301 In addition, the activity of the red microalgal GANAB enzyme was studied, including functional and biochemical characterization using a bioassay, indicating that the enzyme is similar to other eukaryotes ortholog GANAB enzymes. 26987003 9 39 from involvement 1486:1496 arg1 biosynthesis 1516:1527 polysaccharide biosynthesis 1501:1527 polysaccharide biosynthesis 1501:1527 A correlation between polysaccharide production and GANAB activity, indicating its involvement in polysaccharide biosynthesis, is also demonstrated. 26987003 7 40 theme phylogenic 1030:1039 arg1 tree 1041:1044 its phylogenic tree 1026:1044 its phylogenic tree 1026:1044 Phylogenetic analysis revealed its wide distribution across an evolutionarily vast range of organisms; while the α subunit is highly conserved and its phylogenic tree is similar to the taxon evolutionary tree, the β subunit is less conserved and its pattern somewhat differs from the taxon tree. 26987003 0 41 from sp 71:72 arg1 Insight 0:6 Insight 0:6 Insight into glucosidase II from the red marine microalga Porphyridium sp. 0:73 Insight into glucosidase II from the red marine microalga Porphyridium sp. 26987003 8 42 theme GANAB 1223:1227 arg1 enzyme 1229:1234 the red microalgal GANAB enzyme 1204:1234 the red microalgal GANAB enzyme 1204:1234 In addition, the activity of the red microalgal GANAB enzyme was studied, including functional and biochemical characterization using a bioassay, indicating that the enzyme is similar to other eukaryotes ortholog GANAB enzymes. 26987003 5 43 dep using 623:627 arg1 Rhodophyta 611:620 Rhodophyta 611:620 Rhodophyta 611:620 (Rhodophyta) using bioinformatic and biochemical approaches. 26987003 4 44 theme 1,3-glucosidase 516:530 arg1 glycoenzyme 555:565 the α 1,3-glucosidase glucosidase II (GANAB) glycoenzyme 510:565 the α 1,3-glucosidase glucosidase II (GANAB) glycoenzyme in a red marine microalga Porphyridium sp 510:607 We studied the α 1,3-glucosidase glucosidase II (GANAB) glycoenzyme in a red marine microalga Porphyridium sp. 26987003 2 45 theme post-translational 146:163 arg1 modifications 165:177 the most important post-translational modifications 127:177 the most important post-translational modifications that occur in various organisms 127:209 N-glycosylation of proteins is one of the most important post-translational modifications that occur in various organisms, and is of utmost importance for protein function, stability, secretion, and loca-lization. 26987003 9 46 dep correlation 1405:1415 arg1 indicating 1471:1480 indicating 1471:1480 indicating its involvement in polysaccharide biosynthesis 1471:1527 A correlation between polysaccharide production and GANAB activity, indicating its involvement in polysaccharide biosynthesis, is also demonstrated. 26987003 6 47 theme common 756:761 arg1 features 763:770 all the common features 748:770 all the common features of α and β subunits 748:790 The GANAB-gene was found to be highly conserved evolutionarily (compo-sed of all the common features of α and β subunits) and to exhibit similar motifs consistent with that of homolog eukaryotes GANAB genes. 26987003 8 48 theme microalgal 1212:1221 arg1 enzyme 1229:1234 the red microalgal GANAB enzyme 1204:1234 the red microalgal GANAB enzyme 1204:1234 In addition, the activity of the red microalgal GANAB enzyme was studied, including functional and biochemical characterization using a bioassay, indicating that the enzyme is similar to other eukaryotes ortholog GANAB enzymes. 26987003 0 49 theme marine 41:46 arg1 sp 71:72 the red marine microalga Porphyridium sp 33:72 the red marine microalga Porphyridium sp 33:72 Insight into glucosidase II from the red marine microalga Porphyridium sp. 26987003 4 50 theme α 514:514 arg1 glycoenzyme 555:565 the α 1,3-glucosidase glucosidase II (GANAB) glycoenzyme 510:565 the α 1,3-glucosidase glucosidase II (GANAB) glycoenzyme in a red marine microalga Porphyridium sp 510:607 We studied the α 1,3-glucosidase glucosidase II (GANAB) glycoenzyme in a red marine microalga Porphyridium sp. 26987003 2 51 theme important 136:144 arg1 modifications 165:177 the most important post-translational modifications 127:177 the most important post-translational modifications that occur in various organisms 127:209 N-glycosylation of proteins is one of the most important post-translational modifications that occur in various organisms, and is of utmost importance for protein function, stability, secretion, and loca-lization. 26987003 10 52 from N-glycosylation 1623:1637 arg1 microalgae 1687:1696 red microalgae 1683:1696 red microalgae 1683:1696 This study represents a valuable contribution toward understanding the N-glycosylation and polysaccharide biosynthesis pathways in red microalgae. 26987003 9 53 theme GANAB 1455:1459 arg1 activity 1461:1468 GANAB activity 1455:1468 GANAB activity 1455:1468 A correlation between polysaccharide production and GANAB activity, indicating its involvement in polysaccharide biosynthesis, is also demonstrated. 26987003 0 54 theme red 37:39 arg1 sp 71:72 the red marine microalga Porphyridium sp 33:72 the red marine microalga Porphyridium sp 33:72 Insight into glucosidase II from the red marine microalga Porphyridium sp. 26987003 9 55 theme polysaccharide 1501:1514 arg1 biosynthesis 1516:1527 polysaccharide biosynthesis 1501:1527 polysaccharide biosynthesis 1501:1527 A correlation between polysaccharide production and GANAB activity, indicating its involvement in polysaccharide biosynthesis, is also demonstrated. 26987003 10 56 theme red 1683:1685 arg1 microalgae 1687:1696 red microalgae 1683:1696 red microalgae 1683:1696 This study represents a valuable contribution toward understanding the N-glycosylation and polysaccharide biosynthesis pathways in red microalgae. 26987003 6 57 theme similar 808:814 arg1 motifs 816:821 similar motifs 808:821 similar motifs consistent with that of homolog eukaryotes GANAB genes 808:876 The GANAB-gene was found to be highly conserved evolutionarily (compo-sed of all the common features of α and β subunits) and to exhibit similar motifs consistent with that of homolog eukaryotes GANAB genes. 26987003 10 58 from pathways 1671:1678 arg1 microalgae 1687:1696 red microalgae 1683:1696 red microalgae 1683:1696 This study represents a valuable contribution toward understanding the N-glycosylation and polysaccharide biosynthesis pathways in red microalgae. 26987003 8 59 theme enzyme 1229:1234 arg1 activity 1192:1199 the activity 1188:1199 the activity of the red microalgal GANAB enzyme 1188:1234 In addition, the activity of the red microalgal GANAB enzyme was studied, including functional and biochemical characterization using a bioassay, indicating that the enzyme is similar to other eukaryotes ortholog GANAB enzymes. 26987003 4 60 theme glucosidase 532:542 arg1 glycoenzyme 555:565 the α 1,3-glucosidase glucosidase II (GANAB) glycoenzyme 510:565 the α 1,3-glucosidase glucosidase II (GANAB) glycoenzyme in a red marine microalga Porphyridium sp 510:607 We studied the α 1,3-glucosidase glucosidase II (GANAB) glycoenzyme in a red marine microalga Porphyridium sp. 26987003 2 61 theme various 193:199 arg1 organisms 201:209 various organisms 193:209 various organisms 193:209 N-glycosylation of proteins is one of the most important post-translational modifications that occur in various organisms, and is of utmost importance for protein function, stability, secretion, and loca-lization. 26987003 2 62 theme protein 244:250 arg1 function 252:259 protein function 244:259 protein function 244:259 N-glycosylation of proteins is one of the most important post-translational modifications that occur in various organisms, and is of utmost importance for protein function, stability, secretion, and loca-lization. 26987003 7 63 theme α 992:992 arg1 subunit 994:1000 the α subunit 988:1000 the α subunit 988:1000 Phylogenetic analysis revealed its wide distribution across an evolutionarily vast range of organisms; while the α subunit is highly conserved and its phylogenic tree is similar to the taxon evolutionary tree, the β subunit is less conserved and its pattern somewhat differs from the taxon tree. 26987003 3 64 theme N-glycosylation 465:479 arg1 pathway 481:487 the N-glycosylation pathway 461:487 the N-glycosylation pathway in algae 461:496 Although the N-linked glycosylation pathway of proteins has been extensively characterized in mammals and plants, not much information is available regarding the N-glycosylation pathway in algae. 26987003 6 65 dep conserved 709:717 arg1 compo-sed 735:743 compo-sed 735:743 compo-sed 735:743 The GANAB-gene was found to be highly conserved evolutionarily (compo-sed of all the common features of α and β subunits) and to exhibit similar motifs consistent with that of homolog eukaryotes GANAB genes. 26987003 4 66 theme Porphyridium 593:604 arg1 sp 606:607 a red marine microalga Porphyridium sp 570:607 a red marine microalga Porphyridium sp 570:607 We studied the α 1,3-glucosidase glucosidase II (GANAB) glycoenzyme in a red marine microalga Porphyridium sp. 26987003 8 67 theme other 1362:1366 arg1 eukaryotes 1368:1377 other eukaryotes 1362:1377 other eukaryotes 1362:1377 In addition, the activity of the red microalgal GANAB enzyme was studied, including functional and biochemical characterization using a bioassay, indicating that the enzyme is similar to other eukaryotes ortholog GANAB enzymes. 26987003 4 68 theme microalga 583:591 arg1 sp 606:607 a red marine microalga Porphyridium sp 570:607 a red marine microalga Porphyridium sp 570:607 We studied the α 1,3-glucosidase glucosidase II (GANAB) glycoenzyme in a red marine microalga Porphyridium sp. 26987003 0 69 theme Porphyridium 58:69 arg1 sp 71:72 the red marine microalga Porphyridium sp 33:72 the red marine microalga Porphyridium sp 33:72 Insight into glucosidase II from the red marine microalga Porphyridium sp. 26987003 8 70 theme GANAB 1388:1392 arg1 enzymes 1394:1400 similar to other eukaryotes ortholog GANAB enzymes 1351:1400 similar to other eukaryotes ortholog GANAB enzymes 1351:1400 In addition, the activity of the red microalgal GANAB enzyme was studied, including functional and biochemical characterization using a bioassay, indicating that the enzyme is similar to other eukaryotes ortholog GANAB enzymes. 26987003 8 70 theme GANAB 1388:1392 arg1 enzyme 1341:1346 the enzyme 1337:1346 the enzyme 1337:1346 In addition, the activity of the red microalgal GANAB enzyme was studied, including functional and biochemical characterization using a bioassay, indicating that the enzyme is similar to other eukaryotes ortholog GANAB enzymes. 26987003 8 71 theme similar 1351:1357 arg1 enzymes 1394:1400 similar to other eukaryotes ortholog GANAB enzymes 1351:1400 similar to other eukaryotes ortholog GANAB enzymes 1351:1400 In addition, the activity of the red microalgal GANAB enzyme was studied, including functional and biochemical characterization using a bioassay, indicating that the enzyme is similar to other eukaryotes ortholog GANAB enzymes. 26987003 8 71 theme similar 1351:1357 arg1 enzyme 1341:1346 the enzyme 1337:1346 the enzyme 1337:1346 In addition, the activity of the red microalgal GANAB enzyme was studied, including functional and biochemical characterization using a bioassay, indicating that the enzyme is similar to other eukaryotes ortholog GANAB enzymes. 26987003 7 72 theme Phylogenetic 879:890 arg1 analysis 892:899 Phylogenetic analysis 879:899 Phylogenetic analysis 879:899 Phylogenetic analysis revealed its wide distribution across an evolutionarily vast range of organisms; while the α subunit is highly conserved and its phylogenic tree is similar to the taxon evolutionary tree, the β subunit is less conserved and its pattern somewhat differs from the taxon tree. 26987003 0 73 theme microalga 48:56 arg1 sp 71:72 the red marine microalga Porphyridium sp 33:72 the red marine microalga Porphyridium sp 33:72 Insight into glucosidase II from the red marine microalga Porphyridium sp. 26987003 2 74 theme utmost 222:227 arg1 importance 229:238 utmost importance 222:238 utmost importance 222:238 N-glycosylation of proteins is one of the most important post-translational modifications that occur in various organisms, and is of utmost importance for protein function, stability, secretion, and loca-lization. 26987003 7 75 theme taxon 1163:1167 arg1 tree 1169:1172 the taxon tree 1159:1172 the taxon tree 1159:1172 Phylogenetic analysis revealed its wide distribution across an evolutionarily vast range of organisms; while the α subunit is highly conserved and its phylogenic tree is similar to the taxon evolutionary tree, the β subunit is less conserved and its pattern somewhat differs from the taxon tree. 26195816 6 0 theme substrate 871:879 arg1 pocket 889:894 the substrate binding pocket 867:894 the substrate binding pocket 867:894 Subdomain 1 contains the region of LCAT shown to be required for interfacial activation, while subdomain 2 contains the lid and amino acids that shape the substrate binding pocket. 26195816 5 1 theme α/β 622:624 arg1 core 636:639 an α/β hydrolase core 619:639 an α/β hydrolase core with two additional subdomains that play important roles in LCAT function 619:713 The crystal structure reveals that LCAT has an α/β hydrolase core with two additional subdomains that play important roles in LCAT function. 26195816 1 2 theme reverse 129:135 arg1 RCT 160:162 RCT 160:162 RCT 160:162 LCAT is intimately involved in HDL maturation and is a key component of the reverse cholesterol transport (RCT) pathway which removes excess cholesterol molecules from the peripheral tissues to the liver for excretion. 26195816 1 2 theme reverse 129:135 arg1 transport 149:157 reverse cholesterol transport 129:157 the reverse cholesterol transport (RCT) pathway which removes excess cholesterol molecules from the peripheral tissues to the liver for excretion 125:269 LCAT is intimately involved in HDL maturation and is a key component of the reverse cholesterol transport (RCT) pathway which removes excess cholesterol molecules from the peripheral tissues to the liver for excretion. 26195816 1 3 theme peripheral 225:234 arg1 tissues 236:242 the peripheral tissues 221:242 the peripheral tissues 221:242 LCAT is intimately involved in HDL maturation and is a key component of the reverse cholesterol transport (RCT) pathway which removes excess cholesterol molecules from the peripheral tissues to the liver for excretion. 26195816 4 4 theme glycans 503:509 arg1 formation 523:531 complex formation 515:531 complex formation with a Fab fragment from a tool antibody 515:572 Crystallization required enzymatic removal of N-linked glycans and complex formation with a Fab fragment from a tool antibody. 26195816 4 4 theme glycans 503:509 arg1 removal 483:489 enzymatic removal 473:489 enzymatic removal of N-linked glycans 473:509 Crystallization required enzymatic removal of N-linked glycans and complex formation with a Fab fragment from a tool antibody. 26195816 5 5 theme hydrolase 626:634 arg1 core 636:639 an α/β hydrolase core 619:639 an α/β hydrolase core with two additional subdomains that play important roles in LCAT function 619:713 The crystal structure reveals that LCAT has an α/β hydrolase core with two additional subdomains that play important roles in LCAT function. 26195816 6 6 theme interfacial 781:791 arg1 activation 793:802 interfacial activation 781:802 interfacial activation 781:802 Subdomain 1 contains the region of LCAT shown to be required for interfacial activation, while subdomain 2 contains the lid and amino acids that shape the substrate binding pocket. 26195816 1 7 theme cholesterol 137:147 arg1 RCT 160:162 RCT 160:162 RCT 160:162 LCAT is intimately involved in HDL maturation and is a key component of the reverse cholesterol transport (RCT) pathway which removes excess cholesterol molecules from the peripheral tissues to the liver for excretion. 26195816 1 7 theme cholesterol 137:147 arg1 transport 149:157 reverse cholesterol transport 129:157 the reverse cholesterol transport (RCT) pathway which removes excess cholesterol molecules from the peripheral tissues to the liver for excretion 125:269 LCAT is intimately involved in HDL maturation and is a key component of the reverse cholesterol transport (RCT) pathway which removes excess cholesterol molecules from the peripheral tissues to the liver for excretion. 26195816 2 8 with Patients 272:279 arg1 mutations 308:316 loss-of-function LCAT mutations 286:316 loss-of-function LCAT mutations 286:316 Patients with loss-of-function LCAT mutations exhibit low levels of HDL cholesterol and corneal opacity. 26195816 5 9 theme LCAT 701:704 arg1 function 706:713 LCAT function 701:713 LCAT function 701:713 The crystal structure reveals that LCAT has an α/β hydrolase core with two additional subdomains that play important roles in LCAT function. 26195816 4 10 theme N-linked 494:501 arg1 glycans 503:509 N-linked glycans 494:509 N-linked glycans 494:509 Crystallization required enzymatic removal of N-linked glycans and complex formation with a Fab fragment from a tool antibody. 26195816 5 11 theme crystal 579:585 arg1 structure 587:595 The crystal structure 575:595 The crystal structure 575:595 The crystal structure reveals that LCAT has an α/β hydrolase core with two additional subdomains that play important roles in LCAT function. 26195816 4 12 from antibody 565:572 arg1 fragment 544:551 a Fab fragment 538:551 a Fab fragment from a tool antibody 538:572 Crystallization required enzymatic removal of N-linked glycans and complex formation with a Fab fragment from a tool antibody. 26195816 2 13 theme HDL 340:342 arg1 cholesterol 344:354 HDL cholesterol 340:354 HDL cholesterol 340:354 Patients with loss-of-function LCAT mutations exhibit low levels of HDL cholesterol and corneal opacity. 26195816 7 14 theme occurring 919:927 arg1 mutations 929:937 the naturally occurring mutations 905:937 the naturally occurring mutations onto the structure 905:956 Mapping the naturally occurring mutations onto the structure provides insight into how they may affect LCAT enzymatic activity. 26195816 3 15 theme Å 401:401 arg1 structure 411:419 the 2.65 Å crystal structure 392:419 the 2.65 Å crystal structure of the human LCAT protein 392:445 Here we report the 2.65 Å crystal structure of the human LCAT protein. 26195816 1 16 theme transport 149:157 arg1 pathway 165:171 the reverse cholesterol transport (RCT) pathway 125:171 the reverse cholesterol transport (RCT) pathway which removes excess cholesterol molecules from the peripheral tissues to the liver for excretion 125:269 LCAT is intimately involved in HDL maturation and is a key component of the reverse cholesterol transport (RCT) pathway which removes excess cholesterol molecules from the peripheral tissues to the liver for excretion. 26195816 4 17 theme enzymatic 473:481 arg1 removal 483:489 enzymatic removal 473:489 enzymatic removal of N-linked glycans 473:509 Crystallization required enzymatic removal of N-linked glycans and complex formation with a Fab fragment from a tool antibody. 26195816 4 18 theme tool 560:563 arg1 antibody 565:572 a tool antibody 558:572 a tool antibody 558:572 Crystallization required enzymatic removal of N-linked glycans and complex formation with a Fab fragment from a tool antibody. 26195816 0 19 theme high-resolution 4:18 arg1 structure 28:36 The high-resolution crystal structure 0:36 The high-resolution crystal structure of human LCAT 0:50 The high-resolution crystal structure of human LCAT. 26195816 2 20 theme LCAT 303:306 arg1 mutations 308:316 loss-of-function LCAT mutations 286:316 loss-of-function LCAT mutations 286:316 Patients with loss-of-function LCAT mutations exhibit low levels of HDL cholesterol and corneal opacity. 26195816 2 21 theme opacity 368:374 arg1 levels 330:335 low levels 326:335 low levels of HDL cholesterol and corneal opacity 326:374 Patients with loss-of-function LCAT mutations exhibit low levels of HDL cholesterol and corneal opacity. 26195816 6 22 contain contains 728:735 arg2 region 741:746 the region 737:746 the region of LCAT shown to be required for interfacial activation 737:802 Subdomain 1 contains the region of LCAT shown to be required for interfacial activation, while subdomain 2 contains the lid and amino acids that shape the substrate binding pocket. 26195816 6 22 contain contains 728:735 arg1 Subdomain 716:724 Subdomain 1 716:726 Subdomain 1 716:726 Subdomain 1 contains the region of LCAT shown to be required for interfacial activation, while subdomain 2 contains the lid and amino acids that shape the substrate binding pocket. 26195816 4 23 theme Fab 540:542 arg1 fragment 544:551 a Fab fragment 538:551 a Fab fragment from a tool antibody 538:572 Crystallization required enzymatic removal of N-linked glycans and complex formation with a Fab fragment from a tool antibody. 26195816 6 24 theme LCAT 751:754 arg1 region 741:746 the region 737:746 the region of LCAT shown to be required for interfacial activation 737:802 Subdomain 1 contains the region of LCAT shown to be required for interfacial activation, while subdomain 2 contains the lid and amino acids that shape the substrate binding pocket. 26195816 2 25 theme loss-of-function 286:301 arg1 mutations 308:316 loss-of-function LCAT mutations 286:316 loss-of-function LCAT mutations 286:316 Patients with loss-of-function LCAT mutations exhibit low levels of HDL cholesterol and corneal opacity. 26195816 2 26 theme corneal 360:366 arg1 opacity 368:374 corneal opacity 360:374 corneal opacity 360:374 Patients with loss-of-function LCAT mutations exhibit low levels of HDL cholesterol and corneal opacity. 26195816 4 27 link N-linked 494:501 arg1 glycans 503:509 N-linked glycans 494:509 N-linked glycans 494:509 Crystallization required enzymatic removal of N-linked glycans and complex formation with a Fab fragment from a tool antibody. 26195816 1 28 theme pathway 165:171 arg1 component 112:120 a key component 106:120 a key component of the reverse cholesterol transport (RCT) pathway which removes excess cholesterol molecules from the peripheral tissues to the liver for excretion 106:269 LCAT is intimately involved in HDL maturation and is a key component of the reverse cholesterol transport (RCT) pathway which removes excess cholesterol molecules from the peripheral tissues to the liver for excretion. 26195816 1 29 theme HDL 84:86 arg1 maturation 88:97 HDL maturation 84:97 HDL maturation 84:97 LCAT is intimately involved in HDL maturation and is a key component of the reverse cholesterol transport (RCT) pathway which removes excess cholesterol molecules from the peripheral tissues to the liver for excretion. 26195816 5 30 theme important 682:690 arg1 roles 692:696 important roles 682:696 important roles 682:696 The crystal structure reveals that LCAT has an α/β hydrolase core with two additional subdomains that play important roles in LCAT function. 26195816 3 31 theme protein 439:445 arg1 structure 411:419 the 2.65 Å crystal structure 392:419 the 2.65 Å crystal structure of the human LCAT protein 392:445 Here we report the 2.65 Å crystal structure of the human LCAT protein. 26195816 0 32 theme human 41:45 arg1 LCAT 47:50 human LCAT 41:50 human LCAT 41:50 The high-resolution crystal structure of human LCAT. 26195816 6 33 contain contains 823:830 arg2 lid 836:838 lid 836:838 lid 836:838 Subdomain 1 contains the region of LCAT shown to be required for interfacial activation, while subdomain 2 contains the lid and amino acids that shape the substrate binding pocket. 26195816 6 33 contain contains 823:830 arg1 subdomain 811:819 subdomain 2 811:821 subdomain 2 811:821 Subdomain 1 contains the region of LCAT shown to be required for interfacial activation, while subdomain 2 contains the lid and amino acids that shape the substrate binding pocket. 26195816 6 33 contain contains 823:830 arg2 acids 850:854 amino acids 844:854 amino acids 844:854 Subdomain 1 contains the region of LCAT shown to be required for interfacial activation, while subdomain 2 contains the lid and amino acids that shape the substrate binding pocket. 26195816 3 34 theme crystal 403:409 arg1 structure 411:419 the 2.65 Å crystal structure 392:419 the 2.65 Å crystal structure of the human LCAT protein 392:445 Here we report the 2.65 Å crystal structure of the human LCAT protein. 26195816 3 35 theme 2.65 396:399 arg1 structure 411:419 the 2.65 Å crystal structure 392:419 the 2.65 Å crystal structure of the human LCAT protein 392:445 Here we report the 2.65 Å crystal structure of the human LCAT protein. 26195816 4 36 theme complex 515:521 arg1 formation 523:531 complex formation 515:531 complex formation with a Fab fragment from a tool antibody 515:572 Crystallization required enzymatic removal of N-linked glycans and complex formation with a Fab fragment from a tool antibody. 26195816 5 37 contain has 615:617 arg2 core 636:639 an α/β hydrolase core 619:639 an α/β hydrolase core with two additional subdomains that play important roles in LCAT function 619:713 The crystal structure reveals that LCAT has an α/β hydrolase core with two additional subdomains that play important roles in LCAT function. 26195816 5 37 contain has 615:617 arg1 LCAT 610:613 LCAT 610:613 LCAT 610:613 The crystal structure reveals that LCAT has an α/β hydrolase core with two additional subdomains that play important roles in LCAT function. 26195816 1 38 theme excess 187:192 arg1 molecules 206:214 excess cholesterol molecules 187:214 excess cholesterol molecules 187:214 LCAT is intimately involved in HDL maturation and is a key component of the reverse cholesterol transport (RCT) pathway which removes excess cholesterol molecules from the peripheral tissues to the liver for excretion. 26195816 7 39 theme enzymatic 1005:1013 arg1 activity 1015:1022 LCAT enzymatic activity 1000:1022 LCAT enzymatic activity 1000:1022 Mapping the naturally occurring mutations onto the structure provides insight into how they may affect LCAT enzymatic activity. 26195816 6 40 theme amino 844:848 arg1 acids 850:854 amino acids 844:854 amino acids 844:854 Subdomain 1 contains the region of LCAT shown to be required for interfacial activation, while subdomain 2 contains the lid and amino acids that shape the substrate binding pocket. 26195816 0 41 theme LCAT 47:50 arg1 structure 28:36 The high-resolution crystal structure 0:36 The high-resolution crystal structure of human LCAT 0:50 The high-resolution crystal structure of human LCAT. 26195816 6 42 dep lid 836:838 arg1 the 832:834 the 832:834 the 832:834 Subdomain 1 contains the region of LCAT shown to be required for interfacial activation, while subdomain 2 contains the lid and amino acids that shape the substrate binding pocket. 26195816 5 43 theme additional 650:659 arg1 subdomains 661:670 two additional subdomains 646:670 two additional subdomains that play important roles in LCAT function 646:713 The crystal structure reveals that LCAT has an α/β hydrolase core with two additional subdomains that play important roles in LCAT function. 26195816 2 44 theme low 326:328 arg1 levels 330:335 low levels 326:335 low levels of HDL cholesterol and corneal opacity 326:374 Patients with loss-of-function LCAT mutations exhibit low levels of HDL cholesterol and corneal opacity. 26195816 1 45 theme key 108:110 arg1 component 112:120 a key component 106:120 a key component of the reverse cholesterol transport (RCT) pathway which removes excess cholesterol molecules from the peripheral tissues to the liver for excretion 106:269 LCAT is intimately involved in HDL maturation and is a key component of the reverse cholesterol transport (RCT) pathway which removes excess cholesterol molecules from the peripheral tissues to the liver for excretion. 26195816 1 46 theme cholesterol 194:204 arg1 molecules 206:214 excess cholesterol molecules 187:214 excess cholesterol molecules 187:214 LCAT is intimately involved in HDL maturation and is a key component of the reverse cholesterol transport (RCT) pathway which removes excess cholesterol molecules from the peripheral tissues to the liver for excretion. 26195816 7 47 theme LCAT 1000:1003 arg1 activity 1015:1022 LCAT enzymatic activity 1000:1022 LCAT enzymatic activity 1000:1022 Mapping the naturally occurring mutations onto the structure provides insight into how they may affect LCAT enzymatic activity. 26195816 4 48 with removal 483:489 arg1 fragment 544:551 a Fab fragment 538:551 a Fab fragment from a tool antibody 538:572 Crystallization required enzymatic removal of N-linked glycans and complex formation with a Fab fragment from a tool antibody. 26195816 3 49 theme human 428:432 arg1 protein 439:445 the human LCAT protein 424:445 the human LCAT protein 424:445 Here we report the 2.65 Å crystal structure of the human LCAT protein. 26195816 3 50 theme LCAT 434:437 arg1 protein 439:445 the human LCAT protein 424:445 the human LCAT protein 424:445 Here we report the 2.65 Å crystal structure of the human LCAT protein. 26195816 5 51 with core 636:639 arg1 subdomains 661:670 two additional subdomains 646:670 two additional subdomains that play important roles in LCAT function 646:713 The crystal structure reveals that LCAT has an α/β hydrolase core with two additional subdomains that play important roles in LCAT function. 26195816 6 52 theme binding 881:887 arg1 pocket 889:894 the substrate binding pocket 867:894 the substrate binding pocket 867:894 Subdomain 1 contains the region of LCAT shown to be required for interfacial activation, while subdomain 2 contains the lid and amino acids that shape the substrate binding pocket. 26195816 0 53 theme crystal 20:26 arg1 structure 28:36 The high-resolution crystal structure 0:36 The high-resolution crystal structure of human LCAT 0:50 The high-resolution crystal structure of human LCAT. 26195816 4 54 with formation 523:531 arg1 fragment 544:551 a Fab fragment 538:551 a Fab fragment from a tool antibody 538:572 Crystallization required enzymatic removal of N-linked glycans and complex formation with a Fab fragment from a tool antibody. 26195816 2 55 theme cholesterol 344:354 arg1 levels 330:335 low levels 326:335 low levels of HDL cholesterol and corneal opacity 326:374 Patients with loss-of-function LCAT mutations exhibit low levels of HDL cholesterol and corneal opacity. 26195816 6 56 dep contains 728:735 arg1 while 805:809 while 805:809 while 805:809 Subdomain 1 contains the region of LCAT shown to be required for interfacial activation, while subdomain 2 contains the lid and amino acids that shape the substrate binding pocket. 23782392 15 0 theme other 2042:2046 arg1 enzyme 2048:2053 the other enzyme 2038:2053 the other enzyme belonging to a different family under a defective condition 2038:2113 In addition, an α-l-arabinofuranosidase activity derived from SlArf/Xyl2 would be essential in young organ development and the action of the enzyme could be restored by the other enzyme belonging to a different family under a defective condition. 23782392 15 1 theme α-l-arabinofuranosidase 1885:1907 arg1 essential 1951:1959 essential 1951:1959 essential 1951:1959 In addition, an α-l-arabinofuranosidase activity derived from SlArf/Xyl2 would be essential in young organ development and the action of the enzyme could be restored by the other enzyme belonging to a different family under a defective condition. 23782392 15 1 theme α-l-arabinofuranosidase 1885:1907 arg1 activity 1909:1916 an α-l-arabinofuranosidase activity 1882:1916 an α-l-arabinofuranosidase activity derived from SlArf/Xyl2 1882:1940 In addition, an α-l-arabinofuranosidase activity derived from SlArf/Xyl2 would be essential in young organ development and the action of the enzyme could be restored by the other enzyme belonging to a different family under a defective condition. 23782392 13 2 theme recombinant 1601:1611 arg1 SlArf/Xyl2 1613:1622 recombinant SlArf/Xyl2 1601:1622 recombinant SlArf/Xyl2 1601:1622 The ability of recombinant SlArf/Xyl2 to hydrolyze both arabinan and arabinoxylan is nearly identical to that of α-l-arabinofuranosidases belonging to family 51. 23782392 12 3 theme SlArf/Xyl2-suppressed 1557:1577 arg1 fruit 1579:1583 SlArf/Xyl2-suppressed fruit 1557:1583 SlArf/Xyl2-suppressed fruit 1557:1583 Increment of a family 51 α-l-arabinofuranosidase expression rather than that of family 3 resulted in a restoring the activity in SlArf/Xyl2-suppressed fruit. 23782392 1 4 theme glycoside 315:323 arg1 family 335:340 glycoside hydrolase family 3 315:342 glycoside hydrolase family 3 315:342 Four cDNA clones (SlArf/Xyl1-4) encoding α-l-arabinofuranosidase/β-xylosidase belonging to glycoside hydrolase family 3 were obtained from tomato (Solanum lycopersicum) fruit. 23782392 9 5 theme enzyme 1052:1057 arg1 activities 1059:1068 Neither enzyme activities 1044:1068 activities 1059:1068 Neither enzyme activities were detected for the SlArf/Xyl3 protein under the same conditions. 23782392 3 6 from fruit 508:512 arg1 low 501:503 low 501:503 low 501:503 Its level was particularly high in flower and leaves but low in fruit. 23782392 15 7 from essential 1951:1959 arg1 addition 1872:1879 addition 1872:1879 addition 1872:1879 In addition, an α-l-arabinofuranosidase activity derived from SlArf/Xyl2 would be essential in young organ development and the action of the enzyme could be restored by the other enzyme belonging to a different family under a defective condition. 23782392 15 7 from essential 1951:1959 arg1 development 1976:1986 young organ development 1964:1986 young organ development 1964:1986 In addition, an α-l-arabinofuranosidase activity derived from SlArf/Xyl2 would be essential in young organ development and the action of the enzyme could be restored by the other enzyme belonging to a different family under a defective condition. 23782392 9 8 theme same 1121:1124 arg1 conditions 1126:1135 the same conditions 1117:1135 the same conditions 1117:1135 Neither enzyme activities were detected for the SlArf/Xyl3 protein under the same conditions. 23782392 9 9 theme SlArf/Xyl3 1092:1101 arg1 protein 1103:1109 the SlArf/Xyl3 protein 1088:1109 the SlArf/Xyl3 protein 1088:1109 Neither enzyme activities were detected for the SlArf/Xyl3 protein under the same conditions. 23782392 15 10 from development 1976:1986 arg1 essential 1951:1959 essential 1951:1959 essential 1951:1959 In addition, an α-l-arabinofuranosidase activity derived from SlArf/Xyl2 would be essential in young organ development and the action of the enzyme could be restored by the other enzyme belonging to a different family under a defective condition. 23782392 15 10 from development 1976:1986 arg1 activity 1909:1916 an α-l-arabinofuranosidase activity 1882:1916 an α-l-arabinofuranosidase activity derived from SlArf/Xyl2 1882:1940 In addition, an α-l-arabinofuranosidase activity derived from SlArf/Xyl2 would be essential in young organ development and the action of the enzyme could be restored by the other enzyme belonging to a different family under a defective condition. 23782392 8 11 contain possessed 995:1003 arg2 activity 1020:1027 a β-xylosidase activity 1005:1027 a β-xylosidase activity 1005:1027 The SlArf/Xyl1 and 2 recombinant proteins showed a bi-functional activity of α-l-arabinofuranosidase/β-xylosidase while the SlArf/Xyl4 protein possessed a β-xylosidase activity predominantly. 23782392 8 11 contain possessed 995:1003 arg1 protein 987:993 the SlArf/Xyl4 protein 972:993 the SlArf/Xyl4 protein 972:993 The SlArf/Xyl1 and 2 recombinant proteins showed a bi-functional activity of α-l-arabinofuranosidase/β-xylosidase while the SlArf/Xyl4 protein possessed a β-xylosidase activity predominantly. 23782392 0 12 theme enzyme 216:221 arg1 suppression 197:207 antisense suppression 187:207 antisense suppression of the enzyme 187:221 Heterologous expression of tomato glycoside hydrolase family 3 α-L-arabinofuranosidase/β-xylosidases in tobacco suspension cultured cells and synergic action of a family 51 isozyme under antisense suppression of the enzyme. 23782392 11 13 from changes 1347:1353 arg1 activities 1369:1378 the enzyme activities 1358:1378 the enzyme activities 1358:1378 Antisense suppression of SlArf/Xyl2 resulted in no apparent changes in the enzyme activities, monosaccharide composition or fruit phenotype. 23782392 6 14 theme SlArf/Xyl2 683:692 arg1 SlArf/Xyl4 671:680 SlArf/Xyl4 671:680 SlArf/Xyl4 671:680 Comparison with SlArf/Xyl4, SlArf/Xyl2 expression was observed in earlier stages. 23782392 6 14 theme SlArf/Xyl2 683:692 arg1 expression 694:703 SlArf/Xyl2 expression 683:703 SlArf/Xyl2 expression 683:703 Comparison with SlArf/Xyl4, SlArf/Xyl2 expression was observed in earlier stages. 23782392 14 15 theme hydrolyzing 1848:1858 arg1 enzymes 1860:1866 active cell wall hydrolyzing enzymes 1831:1866 active cell wall hydrolyzing enzymes 1831:1866 Our results suggested that BY-2 cells are a useful expression system for obtaining active cell wall hydrolyzing enzymes. 23782392 10 16 theme tomato 1248:1253 arg1 polysaccharides 1270:1284 tomato hemicellulosic polysaccharides 1248:1284 tomato hemicellulosic polysaccharides 1248:1284 Although SlArf/Xyl2 possessed a bi-functional activity, it preferentially hydrolyzed arabinosyl residues from tomato hemicellulosic polysaccharides. 23782392 0 17 theme tobacco 104:110 arg1 suspension 112:121 tobacco suspension 104:121 tobacco suspension 104:121 Heterologous expression of tomato glycoside hydrolase family 3 α-L-arabinofuranosidase/β-xylosidases in tobacco suspension cultured cells and synergic action of a family 51 isozyme under antisense suppression of the enzyme. 23782392 14 18 theme cell 1838:1841 arg1 enzymes 1860:1866 active cell wall hydrolyzing enzymes 1831:1866 active cell wall hydrolyzing enzymes 1831:1866 Our results suggested that BY-2 cells are a useful expression system for obtaining active cell wall hydrolyzing enzymes. 23782392 5 19 theme developmental 616:628 arg1 stage 630:634 early developmental stage 610:634 early developmental stage in various organs 610:652 On the contrary, SlArf/Xyl2 and 4 were expressed in early developmental stage in various organs. 23782392 5 20 from stage 630:634 arg1 organs 647:652 various organs 639:652 various organs 639:652 On the contrary, SlArf/Xyl2 and 4 were expressed in early developmental stage in various organs. 23782392 0 21 theme cultured 123:130 arg1 cells 132:136 cultured cells 123:136 cultured cells 123:136 Heterologous expression of tomato glycoside hydrolase family 3 α-L-arabinofuranosidase/β-xylosidases in tobacco suspension cultured cells and synergic action of a family 51 isozyme under antisense suppression of the enzyme. 23782392 15 22 attach derived 1918:1924 arg2 activity 1909:1916 an α-l-arabinofuranosidase activity 1882:1916 an α-l-arabinofuranosidase activity derived from SlArf/Xyl2 1882:1940 In addition, an α-l-arabinofuranosidase activity derived from SlArf/Xyl2 would be essential in young organ development and the action of the enzyme could be restored by the other enzyme belonging to a different family under a defective condition. 23782392 15 22 attach derived 1918:1924 arg1 SlArf/Xyl2 1931:1940 SlArf/Xyl2 1931:1940 SlArf/Xyl2 1931:1940 In addition, an α-l-arabinofuranosidase activity derived from SlArf/Xyl2 would be essential in young organ development and the action of the enzyme could be restored by the other enzyme belonging to a different family under a defective condition. 23782392 15 22 attach derived 1918:1924 arg2 essential 1951:1959 essential 1951:1959 essential 1951:1959 In addition, an α-l-arabinofuranosidase activity derived from SlArf/Xyl2 would be essential in young organ development and the action of the enzyme could be restored by the other enzyme belonging to a different family under a defective condition. 23782392 15 23 theme enzyme 2010:2015 arg1 action 1996:2001 the action 1992:2001 the action of the enzyme 1992:2015 In addition, an α-l-arabinofuranosidase activity derived from SlArf/Xyl2 would be essential in young organ development and the action of the enzyme could be restored by the other enzyme belonging to a different family under a defective condition. 23782392 8 24 theme α-l-arabinofuranosidase/β-xylosidase 929:964 arg1 activity 917:924 a bi-functional activity 901:924 a bi-functional activity of α-l-arabinofuranosidase/β-xylosidase 901:964 The SlArf/Xyl1 and 2 recombinant proteins showed a bi-functional activity of α-l-arabinofuranosidase/β-xylosidase while the SlArf/Xyl4 protein possessed a β-xylosidase activity predominantly. 23782392 12 25 theme family 1443:1448 arg1 expression 1477:1486 a family 51 α-l-arabinofuranosidase expression 1441:1486 a family 51 α-l-arabinofuranosidase expression rather than that of family 3 1441:1515 Increment of a family 51 α-l-arabinofuranosidase expression rather than that of family 3 resulted in a restoring the activity in SlArf/Xyl2-suppressed fruit. 23782392 2 26 theme various 428:434 arg1 organs 436:441 various organs 428:441 various organs 428:441 SlArf/Xyl1 was expressed in various organs. 23782392 0 27 theme Heterologous 0:11 arg1 expression 13:22 Heterologous expression 0:22 Heterologous expression of tomato glycoside hydrolase family 3 0:61 Heterologous expression of tomato glycoside hydrolase family 3 α-L-arabinofuranosidase/β-xylosidases in tobacco suspension cultured cells and synergic action of a family 51 isozyme under antisense suppression of the enzyme. 23782392 1 28 theme hydrolase 325:333 arg1 family 335:340 glycoside hydrolase family 3 315:342 glycoside hydrolase family 3 315:342 Four cDNA clones (SlArf/Xyl1-4) encoding α-l-arabinofuranosidase/β-xylosidase belonging to glycoside hydrolase family 3 were obtained from tomato (Solanum lycopersicum) fruit. 23782392 12 29 from activity 1545:1552 arg1 fruit 1579:1583 SlArf/Xyl2-suppressed fruit 1557:1583 SlArf/Xyl2-suppressed fruit 1557:1583 Increment of a family 51 α-l-arabinofuranosidase expression rather than that of family 3 resulted in a restoring the activity in SlArf/Xyl2-suppressed fruit. 23782392 12 30 theme α-l-arabinofuranosidase 1453:1475 arg1 expression 1477:1486 a family 51 α-l-arabinofuranosidase expression 1441:1486 a family 51 α-l-arabinofuranosidase expression rather than that of family 3 1441:1515 Increment of a family 51 α-l-arabinofuranosidase expression rather than that of family 3 resulted in a restoring the activity in SlArf/Xyl2-suppressed fruit. 23782392 7 31 theme suspension 825:834 arg1 cells 845:849 BY-2 tobacco (Nicotiana tabacum) suspension cultured cells 792:849 BY-2 tobacco (Nicotiana tabacum) suspension cultured cells 792:849 The active recombinant proteins were obtained by using BY-2 tobacco (Nicotiana tabacum) suspension cultured cells. 23782392 11 32 theme enzyme 1362:1367 arg1 activities 1369:1378 the enzyme activities 1358:1378 the enzyme activities 1358:1378 Antisense suppression of SlArf/Xyl2 resulted in no apparent changes in the enzyme activities, monosaccharide composition or fruit phenotype. 23782392 0 33 theme glycoside 34:42 arg1 family 54:59 tomato glycoside hydrolase family 3 27:61 tomato glycoside hydrolase family 3 27:61 Heterologous expression of tomato glycoside hydrolase family 3 α-L-arabinofuranosidase/β-xylosidases in tobacco suspension cultured cells and synergic action of a family 51 isozyme under antisense suppression of the enzyme. 23782392 11 34 theme fruit 1411:1415 arg1 phenotype 1417:1425 fruit phenotype 1411:1425 fruit phenotype 1411:1425 Antisense suppression of SlArf/Xyl2 resulted in no apparent changes in the enzyme activities, monosaccharide composition or fruit phenotype. 23782392 13 35 theme SlArf/Xyl2 1613:1622 arg1 identical 1678:1686 identical 1678:1686 identical 1678:1686 The ability of recombinant SlArf/Xyl2 to hydrolyze both arabinan and arabinoxylan is nearly identical to that of α-l-arabinofuranosidases belonging to family 51. 23782392 13 35 theme SlArf/Xyl2 1613:1622 arg1 ability 1590:1596 The ability 1586:1596 The ability of recombinant SlArf/Xyl2 to hydrolyze both arabinan and arabinoxylan 1586:1666 The ability of recombinant SlArf/Xyl2 to hydrolyze both arabinan and arabinoxylan is nearly identical to that of α-l-arabinofuranosidases belonging to family 51. 23782392 0 36 theme family 54:59 arg1 expression 13:22 Heterologous expression 0:22 Heterologous expression of tomato glycoside hydrolase family 3 0:61 Heterologous expression of tomato glycoside hydrolase family 3 α-L-arabinofuranosidase/β-xylosidases in tobacco suspension cultured cells and synergic action of a family 51 isozyme under antisense suppression of the enzyme. 23782392 1 37 theme tomato 363:368 arg1 fruit 393:397 tomato (Solanum lycopersicum) fruit 363:397 tomato (Solanum lycopersicum) fruit 363:397 Four cDNA clones (SlArf/Xyl1-4) encoding α-l-arabinofuranosidase/β-xylosidase belonging to glycoside hydrolase family 3 were obtained from tomato (Solanum lycopersicum) fruit. 23782392 1 38 theme Solanum 371:377 arg1 fruit 393:397 tomato (Solanum lycopersicum) fruit 363:397 tomato (Solanum lycopersicum) fruit 363:397 Four cDNA clones (SlArf/Xyl1-4) encoding α-l-arabinofuranosidase/β-xylosidase belonging to glycoside hydrolase family 3 were obtained from tomato (Solanum lycopersicum) fruit. 23782392 7 39 theme BY-2 792:795 arg1 tabacum 816:822 Nicotiana tabacum 806:822 Nicotiana tabacum 806:822 The active recombinant proteins were obtained by using BY-2 tobacco (Nicotiana tabacum) suspension cultured cells. 23782392 7 39 theme BY-2 792:795 arg1 tobacco 797:803 BY-2 tobacco 792:803 BY-2 tobacco (Nicotiana tabacum) suspension cultured cells 792:849 The active recombinant proteins were obtained by using BY-2 tobacco (Nicotiana tabacum) suspension cultured cells. 23782392 11 40 theme Antisense 1287:1295 arg1 suppression 1297:1307 Antisense suppression 1287:1307 Antisense suppression of SlArf/Xyl2 1287:1321 Antisense suppression of SlArf/Xyl2 resulted in no apparent changes in the enzyme activities, monosaccharide composition or fruit phenotype. 23782392 14 41 theme wall 1843:1846 arg1 enzymes 1860:1866 active cell wall hydrolyzing enzymes 1831:1866 active cell wall hydrolyzing enzymes 1831:1866 Our results suggested that BY-2 cells are a useful expression system for obtaining active cell wall hydrolyzing enzymes. 23782392 10 42 from polysaccharides 1270:1284 arg1 residues 1234:1241 arabinosyl residues 1223:1241 arabinosyl residues from tomato hemicellulosic polysaccharides 1223:1284 Although SlArf/Xyl2 possessed a bi-functional activity, it preferentially hydrolyzed arabinosyl residues from tomato hemicellulosic polysaccharides. 23782392 7 43 theme recombinant 748:758 arg1 proteins 760:767 The active recombinant proteins 737:767 The active recombinant proteins 737:767 The active recombinant proteins were obtained by using BY-2 tobacco (Nicotiana tabacum) suspension cultured cells. 23782392 6 44 located observed 709:716 arg1 stages 729:734 earlier stages 721:734 earlier stages 721:734 Comparison with SlArf/Xyl4, SlArf/Xyl2 expression was observed in earlier stages. 23782392 6 44 located observed 709:716 arg2 Comparison 655:664 Comparison 655:664 Comparison with SlArf/Xyl4, SlArf/Xyl2 expression 655:703 Comparison with SlArf/Xyl4, SlArf/Xyl2 expression was observed in earlier stages. 23782392 15 45 theme young 1964:1968 arg1 development 1976:1986 young organ development 1964:1986 young organ development 1964:1986 In addition, an α-l-arabinofuranosidase activity derived from SlArf/Xyl2 would be essential in young organ development and the action of the enzyme could be restored by the other enzyme belonging to a different family under a defective condition. 23782392 15 46 theme defective 2095:2103 arg1 condition 2105:2113 a defective condition 2093:2113 a defective condition 2093:2113 In addition, an α-l-arabinofuranosidase activity derived from SlArf/Xyl2 would be essential in young organ development and the action of the enzyme could be restored by the other enzyme belonging to a different family under a defective condition. 23782392 15 47 theme different 2070:2078 arg1 family 2080:2085 a different family 2068:2085 a different family under a defective condition 2068:2113 In addition, an α-l-arabinofuranosidase activity derived from SlArf/Xyl2 would be essential in young organ development and the action of the enzyme could be restored by the other enzyme belonging to a different family under a defective condition. 23782392 0 48 theme family 163:168 arg1 isozyme 173:179 a family 51 isozyme 161:179 a family 51 isozyme 161:179 Heterologous expression of tomato glycoside hydrolase family 3 α-L-arabinofuranosidase/β-xylosidases in tobacco suspension cultured cells and synergic action of a family 51 isozyme under antisense suppression of the enzyme. 23782392 7 49 theme active 741:746 arg1 proteins 760:767 The active recombinant proteins 737:767 The active recombinant proteins 737:767 The active recombinant proteins were obtained by using BY-2 tobacco (Nicotiana tabacum) suspension cultured cells. 23782392 1 50 theme cDNA 229:232 arg1 SlArf/Xyl1-4 242:253 SlArf/Xyl1-4 242:253 SlArf/Xyl1-4 242:253 Four cDNA clones (SlArf/Xyl1-4) encoding α-l-arabinofuranosidase/β-xylosidase belonging to glycoside hydrolase family 3 were obtained from tomato (Solanum lycopersicum) fruit. 23782392 1 50 theme cDNA 229:232 arg1 clones 234:239 Four cDNA clones 224:239 Four cDNA clones (SlArf/Xyl1-4) encoding α-l-arabinofuranosidase/β-xylosidase belonging to glycoside hydrolase family 3 224:342 Four cDNA clones (SlArf/Xyl1-4) encoding α-l-arabinofuranosidase/β-xylosidase belonging to glycoside hydrolase family 3 were obtained from tomato (Solanum lycopersicum) fruit. 23782392 14 51 theme useful 1792:1797 arg1 system 1810:1815 a useful expression system 1790:1815 a useful expression system for obtaining active cell wall hydrolyzing enzymes 1790:1866 Our results suggested that BY-2 cells are a useful expression system for obtaining active cell wall hydrolyzing enzymes. 23782392 14 51 theme useful 1792:1797 arg1 cells 1780:1784 BY-2 cells 1775:1784 BY-2 cells 1775:1784 Our results suggested that BY-2 cells are a useful expression system for obtaining active cell wall hydrolyzing enzymes. 23782392 0 52 theme isozyme 173:179 arg1 action 151:156 synergic action 142:156 synergic action 142:156 Heterologous expression of tomato glycoside hydrolase family 3 α-L-arabinofuranosidase/β-xylosidases in tobacco suspension cultured cells and synergic action of a family 51 isozyme under antisense suppression of the enzyme. 23782392 0 52 theme isozyme 173:179 arg1 suspension 112:121 tobacco suspension 104:121 tobacco suspension 104:121 Heterologous expression of tomato glycoside hydrolase family 3 α-L-arabinofuranosidase/β-xylosidases in tobacco suspension cultured cells and synergic action of a family 51 isozyme under antisense suppression of the enzyme. 23782392 14 53 theme active 1831:1836 arg1 enzymes 1860:1866 active cell wall hydrolyzing enzymes 1831:1866 active cell wall hydrolyzing enzymes 1831:1866 Our results suggested that BY-2 cells are a useful expression system for obtaining active cell wall hydrolyzing enzymes. 23782392 0 54 theme antisense 187:195 arg1 suppression 197:207 antisense suppression 187:207 antisense suppression of the enzyme 187:221 Heterologous expression of tomato glycoside hydrolase family 3 α-L-arabinofuranosidase/β-xylosidases in tobacco suspension cultured cells and synergic action of a family 51 isozyme under antisense suppression of the enzyme. 23782392 14 55 theme BY-2 1775:1778 arg1 system 1810:1815 a useful expression system 1790:1815 a useful expression system for obtaining active cell wall hydrolyzing enzymes 1790:1866 Our results suggested that BY-2 cells are a useful expression system for obtaining active cell wall hydrolyzing enzymes. 23782392 14 55 theme BY-2 1775:1778 arg1 cells 1780:1784 BY-2 cells 1775:1784 BY-2 cells 1775:1784 Our results suggested that BY-2 cells are a useful expression system for obtaining active cell wall hydrolyzing enzymes. 23782392 12 56 theme that 1500:1503 arg1 Increment 1428:1436 Increment 1428:1436 Increment of a family 51 α-l-arabinofuranosidase expression rather than that of family 3 1428:1515 Increment of a family 51 α-l-arabinofuranosidase expression rather than that of family 3 resulted in a restoring the activity in SlArf/Xyl2-suppressed fruit. 23782392 11 57 from composition 1396:1406 arg1 activities 1369:1378 the enzyme activities 1358:1378 the enzyme activities 1358:1378 Antisense suppression of SlArf/Xyl2 resulted in no apparent changes in the enzyme activities, monosaccharide composition or fruit phenotype. 23782392 1 58 theme lycopersicum 379:390 arg1 fruit 393:397 tomato (Solanum lycopersicum) fruit 363:397 tomato (Solanum lycopersicum) fruit 363:397 Four cDNA clones (SlArf/Xyl1-4) encoding α-l-arabinofuranosidase/β-xylosidase belonging to glycoside hydrolase family 3 were obtained from tomato (Solanum lycopersicum) fruit. 23782392 8 59 theme recombinant 873:883 arg1 proteins 885:892 2 recombinant proteins 871:892 2 recombinant proteins 871:892 The SlArf/Xyl1 and 2 recombinant proteins showed a bi-functional activity of α-l-arabinofuranosidase/β-xylosidase while the SlArf/Xyl4 protein possessed a β-xylosidase activity predominantly. 23782392 10 60 contain possessed 1158:1166 arg1 SlArf/Xyl2 1147:1156 SlArf/Xyl2 1147:1156 SlArf/Xyl2 1147:1156 Although SlArf/Xyl2 possessed a bi-functional activity, it preferentially hydrolyzed arabinosyl residues from tomato hemicellulosic polysaccharides. 23782392 10 60 contain possessed 1158:1166 arg2 activity 1184:1191 a bi-functional activity 1168:1191 a bi-functional activity 1168:1191 Although SlArf/Xyl2 possessed a bi-functional activity, it preferentially hydrolyzed arabinosyl residues from tomato hemicellulosic polysaccharides. 23782392 10 61 theme bi-functional 1170:1182 arg1 activity 1184:1191 a bi-functional activity 1168:1191 a bi-functional activity 1168:1191 Although SlArf/Xyl2 possessed a bi-functional activity, it preferentially hydrolyzed arabinosyl residues from tomato hemicellulosic polysaccharides. 23782392 9 62 dep activities 1059:1068 arg1 Neither 1044:1050 Neither 1044:1050 Neither 1044:1050 Neither enzyme activities were detected for the SlArf/Xyl3 protein under the same conditions. 23782392 0 63 theme synergic 142:149 arg1 action 151:156 synergic action 142:156 synergic action 142:156 Heterologous expression of tomato glycoside hydrolase family 3 α-L-arabinofuranosidase/β-xylosidases in tobacco suspension cultured cells and synergic action of a family 51 isozyme under antisense suppression of the enzyme. 23782392 10 64 theme arabinosyl 1223:1232 arg1 residues 1234:1241 arabinosyl residues 1223:1241 arabinosyl residues from tomato hemicellulosic polysaccharides 1223:1284 Although SlArf/Xyl2 possessed a bi-functional activity, it preferentially hydrolyzed arabinosyl residues from tomato hemicellulosic polysaccharides. 23782392 5 65 theme various 639:645 arg1 organs 647:652 various organs 639:652 various organs 639:652 On the contrary, SlArf/Xyl2 and 4 were expressed in early developmental stage in various organs. 23782392 11 66 theme SlArf/Xyl2 1312:1321 arg1 suppression 1297:1307 Antisense suppression 1287:1307 Antisense suppression of SlArf/Xyl2 1287:1321 Antisense suppression of SlArf/Xyl2 resulted in no apparent changes in the enzyme activities, monosaccharide composition or fruit phenotype. 23782392 8 67 theme bi-functional 903:915 arg1 activity 917:924 a bi-functional activity 901:924 a bi-functional activity of α-l-arabinofuranosidase/β-xylosidase 901:964 The SlArf/Xyl1 and 2 recombinant proteins showed a bi-functional activity of α-l-arabinofuranosidase/β-xylosidase while the SlArf/Xyl4 protein possessed a β-xylosidase activity predominantly. 23782392 14 68 theme expression 1799:1808 arg1 system 1810:1815 a useful expression system 1790:1815 a useful expression system for obtaining active cell wall hydrolyzing enzymes 1790:1866 Our results suggested that BY-2 cells are a useful expression system for obtaining active cell wall hydrolyzing enzymes. 23782392 14 68 theme expression 1799:1808 arg1 cells 1780:1784 BY-2 cells 1775:1784 BY-2 cells 1775:1784 Our results suggested that BY-2 cells are a useful expression system for obtaining active cell wall hydrolyzing enzymes. 23782392 0 69 dep suspension 112:121 arg1 cells 132:136 cultured cells 123:136 cultured cells 123:136 Heterologous expression of tomato glycoside hydrolase family 3 α-L-arabinofuranosidase/β-xylosidases in tobacco suspension cultured cells and synergic action of a family 51 isozyme under antisense suppression of the enzyme. 23782392 12 70 theme expression 1477:1486 arg1 Increment 1428:1436 Increment 1428:1436 Increment of a family 51 α-l-arabinofuranosidase expression rather than that of family 3 1428:1515 Increment of a family 51 α-l-arabinofuranosidase expression rather than that of family 3 resulted in a restoring the activity in SlArf/Xyl2-suppressed fruit. 23782392 6 71 with Comparison 655:664 arg1 SlArf/Xyl4 671:680 SlArf/Xyl4 671:680 SlArf/Xyl4 671:680 Comparison with SlArf/Xyl4, SlArf/Xyl2 expression was observed in earlier stages. 23782392 6 71 with Comparison 655:664 arg1 expression 694:703 SlArf/Xyl2 expression 683:703 SlArf/Xyl2 expression 683:703 Comparison with SlArf/Xyl4, SlArf/Xyl2 expression was observed in earlier stages. 23782392 6 72 theme earlier 721:727 arg1 stages 729:734 earlier stages 721:734 earlier stages 721:734 Comparison with SlArf/Xyl4, SlArf/Xyl2 expression was observed in earlier stages. 23782392 0 73 theme tomato 27:32 arg1 family 54:59 tomato glycoside hydrolase family 3 27:61 tomato glycoside hydrolase family 3 27:61 Heterologous expression of tomato glycoside hydrolase family 3 α-L-arabinofuranosidase/β-xylosidases in tobacco suspension cultured cells and synergic action of a family 51 isozyme under antisense suppression of the enzyme. 23782392 10 74 theme hemicellulosic 1255:1268 arg1 polysaccharides 1270:1284 tomato hemicellulosic polysaccharides 1248:1284 tomato hemicellulosic polysaccharides 1248:1284 Although SlArf/Xyl2 possessed a bi-functional activity, it preferentially hydrolyzed arabinosyl residues from tomato hemicellulosic polysaccharides. 23782392 5 75 theme early 610:614 arg1 stage 630:634 early developmental stage 610:634 early developmental stage in various organs 610:652 On the contrary, SlArf/Xyl2 and 4 were expressed in early developmental stage in various organs. 23782392 11 76 theme apparent 1338:1345 arg1 changes 1347:1353 no apparent changes 1335:1353 no apparent changes in the enzyme activities 1335:1378 Antisense suppression of SlArf/Xyl2 resulted in no apparent changes in the enzyme activities, monosaccharide composition or fruit phenotype. 23782392 11 77 theme monosaccharide 1381:1394 arg1 composition 1396:1406 monosaccharide composition 1381:1406 monosaccharide composition 1381:1406 Antisense suppression of SlArf/Xyl2 resulted in no apparent changes in the enzyme activities, monosaccharide composition or fruit phenotype. 23782392 15 78 theme organ 1970:1974 arg1 development 1976:1986 young organ development 1964:1986 young organ development 1964:1986 In addition, an α-l-arabinofuranosidase activity derived from SlArf/Xyl2 would be essential in young organ development and the action of the enzyme could be restored by the other enzyme belonging to a different family under a defective condition. 23782392 0 79 theme hydrolase 44:52 arg1 family 54:59 tomato glycoside hydrolase family 3 27:61 tomato glycoside hydrolase family 3 27:61 Heterologous expression of tomato glycoside hydrolase family 3 α-L-arabinofuranosidase/β-xylosidases in tobacco suspension cultured cells and synergic action of a family 51 isozyme under antisense suppression of the enzyme. 23782392 7 80 theme cultured 836:843 arg1 cells 845:849 BY-2 tobacco (Nicotiana tabacum) suspension cultured cells 792:849 BY-2 tobacco (Nicotiana tabacum) suspension cultured cells 792:849 The active recombinant proteins were obtained by using BY-2 tobacco (Nicotiana tabacum) suspension cultured cells. 23782392 8 81 theme SlArf/Xyl4 976:985 arg1 protein 987:993 the SlArf/Xyl4 protein 972:993 the SlArf/Xyl4 protein 972:993 The SlArf/Xyl1 and 2 recombinant proteins showed a bi-functional activity of α-l-arabinofuranosidase/β-xylosidase while the SlArf/Xyl4 protein possessed a β-xylosidase activity predominantly. 23782392 3 82 from leaves 490:495 arg1 high 471:474 high 471:474 high 471:474 Its level was particularly high in flower and leaves but low in fruit. 23782392 3 83 from low 501:503 arg1 fruit 508:512 fruit 508:512 fruit 508:512 Its level was particularly high in flower and leaves but low in fruit. 23782392 7 84 theme Nicotiana 806:814 arg1 tabacum 816:822 Nicotiana tabacum 806:822 Nicotiana tabacum 806:822 The active recombinant proteins were obtained by using BY-2 tobacco (Nicotiana tabacum) suspension cultured cells. 23782392 7 84 theme Nicotiana 806:814 arg1 tobacco 797:803 BY-2 tobacco 792:803 BY-2 tobacco (Nicotiana tabacum) suspension cultured cells 792:849 The active recombinant proteins were obtained by using BY-2 tobacco (Nicotiana tabacum) suspension cultured cells. 23782392 8 85 theme β-xylosidase 1007:1018 arg1 activity 1020:1027 a β-xylosidase activity 1005:1027 a β-xylosidase activity 1005:1027 The SlArf/Xyl1 and 2 recombinant proteins showed a bi-functional activity of α-l-arabinofuranosidase/β-xylosidase while the SlArf/Xyl4 protein possessed a β-xylosidase activity predominantly. 23782392 3 86 from high 471:474 arg1 flower 479:484 flower 479:484 flower 479:484 Its level was particularly high in flower and leaves but low in fruit. 23782392 3 86 from high 471:474 arg1 leaves 490:495 leaves 490:495 leaves 490:495 Its level was particularly high in flower and leaves but low in fruit. 23782392 15 87 from addition 1872:1879 arg1 essential 1951:1959 essential 1951:1959 essential 1951:1959 In addition, an α-l-arabinofuranosidase activity derived from SlArf/Xyl2 would be essential in young organ development and the action of the enzyme could be restored by the other enzyme belonging to a different family under a defective condition. 23782392 15 87 from addition 1872:1879 arg1 activity 1909:1916 an α-l-arabinofuranosidase activity 1882:1916 an α-l-arabinofuranosidase activity derived from SlArf/Xyl2 1882:1940 In addition, an α-l-arabinofuranosidase activity derived from SlArf/Xyl2 would be essential in young organ development and the action of the enzyme could be restored by the other enzyme belonging to a different family under a defective condition. 23782392 7 88 theme tobacco 797:803 arg1 cells 845:849 BY-2 tobacco (Nicotiana tabacum) suspension cultured cells 792:849 BY-2 tobacco (Nicotiana tabacum) suspension cultured cells 792:849 The active recombinant proteins were obtained by using BY-2 tobacco (Nicotiana tabacum) suspension cultured cells. 23782392 3 89 from flower 479:484 arg1 high 471:474 high 471:474 high 471:474 Its level was particularly high in flower and leaves but low in fruit. 23782392 11 90 from phenotype 1417:1425 arg1 activities 1369:1378 the enzyme activities 1358:1378 the enzyme activities 1358:1378 Antisense suppression of SlArf/Xyl2 resulted in no apparent changes in the enzyme activities, monosaccharide composition or fruit phenotype. 28780096 12 0 theme ether-linked 2483:2494 arg1 content 2500:2506 ether-linked pCA content 2483:2506 ether-linked pCA content 2483:2506 The results from the in vivo study were similar to the in vitro data, demonstrating the highest total-tract aNDF digestibility (70%; NDF analysis conducted with α-amylase and sodium sulfite) for cows fed the corn silage with the lowest ester- and ether-linked pCA content in the NDF fraction. 28780096 11 1 theme residues 2075:2082 arg1 linkages 2097:2104 chemical linkages 2088:2104 chemical linkages 2088:2104 The lignin content of the plant residues and chemical linkages explained most of the variation in both rate and extent of NDF digestion but not uniformly among forages, ranging from 56 to 99%. 28780096 11 1 theme residues 2075:2082 arg1 content 2054:2060 The lignin content 2043:2060 The lignin content of the plant residues 2043:2082 The lignin content of the plant residues and chemical linkages explained most of the variation in both rate and extent of NDF digestion but not uniformly among forages, ranging from 56 to 99%. 28780096 4 2 theme Twenty-three 747:758 arg1 forages 760:766 Twenty-three forages 747:766 Twenty-three forages 747:766 Twenty-three forages, including conventional and brown midrib corn silages and grasses at various stages of maturity were incubated in vitro for measurement of 24-h and 96-h NDFD. 28780096 4 2 theme Twenty-three 747:758 arg1 silages 814:820 conventional and brown midrib corn silages 779:820 conventional and brown midrib corn silages 779:820 Twenty-three forages, including conventional and brown midrib corn silages and grasses at various stages of maturity were incubated in vitro for measurement of 24-h and 96-h NDFD. 28780096 4 3 theme NDFD 921:924 arg1 measurement 892:902 measurement 892:902 measurement of 24-h and 96-h NDFD 892:924 Twenty-three forages, including conventional and brown midrib corn silages and grasses at various stages of maturity were incubated in vitro for measurement of 24-h and 96-h NDFD. 28780096 3 4 theme p-coumaric 611:620 arg1 linkages 627:634 The ferulic and p-coumaric acid linkages 595:634 The ferulic and p-coumaric acid linkages between ADL and cell wall polysaccharides, rather than the amount of ADL, 595:708 The ferulic and p-coumaric acid linkages between ADL and cell wall polysaccharides, rather than the amount of ADL, might be a better predictor of NDFD. 28780096 3 4 theme p-coumaric 611:620 arg1 predictor 728:736 a better predictor 719:736 a better predictor of NDFD 719:744 The ferulic and p-coumaric acid linkages between ADL and cell wall polysaccharides, rather than the amount of ADL, might be a better predictor of NDFD. 28780096 0 5 theme forages 157:163 arg1 digestion 138:146 digestion 138:146 digestion of grass forages 138:163 Effect of lignin linkages with other plant cell wall components on in vitro and in vivo neutral detergent fiber digestibility and rate of digestion of grass forages. 28780096 1 6 theme para-coumaric 390:402 arg1 FA 429:430 FA 429:430 FA 429:430 The objective of this study was to correlate in vitro and in vivo neutral detergent fiber (NDF) digestibility (NDFD) with the chemical composition of forages and specific chemical linkages, primarily ester- and ether-linked para-coumaric (pCA) and ferulic acids (FA) in forages fed to dairy cattle. 28780096 1 6 theme para-coumaric 390:402 arg1 acids 422:426 ether-linked para-coumaric (pCA) and ferulic acids 377:426 ether-linked para-coumaric (pCA) and ferulic acids (FA) 377:431 The objective of this study was to correlate in vitro and in vivo neutral detergent fiber (NDF) digestibility (NDFD) with the chemical composition of forages and specific chemical linkages, primarily ester- and ether-linked para-coumaric (pCA) and ferulic acids (FA) in forages fed to dairy cattle. 28780096 9 7 link ether-linked 1851:1862 arg1 acid 1872:1875 ether-linked ferulic acid 1851:1875 ether-linked ferulic acid on an NDF basis 1851:1891 Also, Klason lignin and ADL were negatively correlated with ether-linked ferulic acid on an NDF basis. 28780096 1 8 link ether-linked 377:388 arg1 FA 429:430 FA 429:430 FA 429:430 The objective of this study was to correlate in vitro and in vivo neutral detergent fiber (NDF) digestibility (NDFD) with the chemical composition of forages and specific chemical linkages, primarily ester- and ether-linked para-coumaric (pCA) and ferulic acids (FA) in forages fed to dairy cattle. 28780096 1 8 link ether-linked 377:388 arg1 acids 422:426 ether-linked para-coumaric (pCA) and ferulic acids 377:426 ether-linked para-coumaric (pCA) and ferulic acids (FA) 377:431 The objective of this study was to correlate in vitro and in vivo neutral detergent fiber (NDF) digestibility (NDFD) with the chemical composition of forages and specific chemical linkages, primarily ester- and ether-linked para-coumaric (pCA) and ferulic acids (FA) in forages fed to dairy cattle. 28780096 3 9 theme ferulic 599:605 arg1 linkages 627:634 The ferulic and p-coumaric acid linkages 595:634 The ferulic and p-coumaric acid linkages between ADL and cell wall polysaccharides, rather than the amount of ADL, 595:708 The ferulic and p-coumaric acid linkages between ADL and cell wall polysaccharides, rather than the amount of ADL, might be a better predictor of NDFD. 28780096 3 9 theme ferulic 599:605 arg1 predictor 728:736 a better predictor 719:736 a better predictor of NDFD 719:744 The ferulic and p-coumaric acid linkages between ADL and cell wall polysaccharides, rather than the amount of ADL, might be a better predictor of NDFD. 28780096 12 10 theme sodium 2411:2416 arg1 sulfite 2418:2424 sodium sulfite 2411:2424 sodium sulfite 2411:2424 The results from the in vivo study were similar to the in vitro data, demonstrating the highest total-tract aNDF digestibility (70%; NDF analysis conducted with α-amylase and sodium sulfite) for cows fed the corn silage with the lowest ester- and ether-linked pCA content in the NDF fraction. 28780096 12 11 dep in 2257:2258 arg1 vivo 2260:2263 vivo 2260:2263 vivo 2260:2263 The results from the in vivo study were similar to the in vitro data, demonstrating the highest total-tract aNDF digestibility (70%; NDF analysis conducted with α-amylase and sodium sulfite) for cows fed the corn silage with the lowest ester- and ether-linked pCA content in the NDF fraction. 28780096 10 12 theme fiber 1988:1992 arg1 fractions 1994:2002 the measured fiber fractions 1975:2002 the measured fiber fractions on both a dry matter and an NDF basis 1975:2040 Overall, esterified FA and esterified pCA were negatively correlated with all of the measured fiber fractions on both a dry matter and an NDF basis. 28780096 5 13 link ether-linked 1051:1062 arg1 pCA 1064:1066 ether-linked pCA 1051:1066 ether-linked pCA 1051:1066 Undigested and digested residues were analyzed for NDF, acid detergent fiber (ADF), ADL, and Klason lignin (KL); ester- and ether-linked pCA and FA were determined in these fractions. 28780096 10 14 theme NDF 2032:2034 arg1 basis 2036:2040 an NDF basis 2029:2040 an NDF basis 2029:2040 Overall, esterified FA and esterified pCA were negatively correlated with all of the measured fiber fractions on both a dry matter and an NDF basis. 28780096 4 15 theme brown 796:800 arg1 silages 814:820 conventional and brown midrib corn silages 779:820 conventional and brown midrib corn silages 779:820 Twenty-three forages, including conventional and brown midrib corn silages and grasses at various stages of maturity were incubated in vitro for measurement of 24-h and 96-h NDFD. 28780096 0 16 theme neutral 88:94 arg1 digestibility 112:124 in vitro and in vivo neutral detergent fiber digestibility 67:124 in vitro and in vivo neutral detergent fiber digestibility 67:124 Effect of lignin linkages with other plant cell wall components on in vitro and in vivo neutral detergent fiber digestibility and rate of digestion of grass forages. 28780096 5 17 theme Undigested 927:936 arg1 residues 951:958 Undigested and digested residues 927:958 Undigested and digested residues 927:958 Undigested and digested residues were analyzed for NDF, acid detergent fiber (ADF), ADL, and Klason lignin (KL); ester- and ether-linked pCA and FA were determined in these fractions. 28780096 12 18 dep similar 2276:2282 arg1 similar 2276:2282 similar 2276:2282 similar 2276:2282 The results from the in vivo study were similar to the in vitro data, demonstrating the highest total-tract aNDF digestibility (70%; NDF analysis conducted with α-amylase and sodium sulfite) for cows fed the corn silage with the lowest ester- and ether-linked pCA content in the NDF fraction. 28780096 12 18 dep similar 2276:2282 arg1 results 2240:2246 The results 2236:2246 The results from the in vivo study 2236:2269 The results from the in vivo study were similar to the in vitro data, demonstrating the highest total-tract aNDF digestibility (70%; NDF analysis conducted with α-amylase and sodium sulfite) for cows fed the corn silage with the lowest ester- and ether-linked pCA content in the NDF fraction. 28780096 12 18 dep similar 2276:2282 arg1 demonstrating 2306:2318 demonstrating 2306:2318 demonstrating the highest total-tract aNDF digestibility (70%; NDF analysis conducted with α-amylase and sodium sulfite) for cows fed the corn silage with the lowest ester- and ether-linked pCA content in the NDF fraction 2306:2526 The results from the in vivo study were similar to the in vitro data, demonstrating the highest total-tract aNDF digestibility (70%; NDF analysis conducted with α-amylase and sodium sulfite) for cows fed the corn silage with the lowest ester- and ether-linked pCA content in the NDF fraction. 28780096 4 19 theme corn 809:812 arg1 silages 814:820 conventional and brown midrib corn silages 779:820 conventional and brown midrib corn silages 779:820 Twenty-three forages, including conventional and brown midrib corn silages and grasses at various stages of maturity were incubated in vitro for measurement of 24-h and 96-h NDFD. 28780096 1 20 dep para-coumaric 390:402 arg1 pCA 405:407 pCA 405:407 pCA 405:407 The objective of this study was to correlate in vitro and in vivo neutral detergent fiber (NDF) digestibility (NDFD) with the chemical composition of forages and specific chemical linkages, primarily ester- and ether-linked para-coumaric (pCA) and ferulic acids (FA) in forages fed to dairy cattle. 28780096 0 21 theme fiber 106:110 arg1 digestibility 112:124 in vitro and in vivo neutral detergent fiber digestibility 67:124 in vitro and in vivo neutral detergent fiber digestibility 67:124 Effect of lignin linkages with other plant cell wall components on in vitro and in vivo neutral detergent fiber digestibility and rate of digestion of grass forages. 28780096 1 22 theme specific 328:335 arg1 linkages 346:353 specific chemical linkages 328:353 specific chemical linkages 328:353 The objective of this study was to correlate in vitro and in vivo neutral detergent fiber (NDF) digestibility (NDFD) with the chemical composition of forages and specific chemical linkages, primarily ester- and ether-linked para-coumaric (pCA) and ferulic acids (FA) in forages fed to dairy cattle. 28780096 12 23 dep digestibility 2349:2361 arg1 % 2366:2366 70% 2364:2366 70%; NDF analysis conducted with α-amylase and sodium sulfite 2364:2424 The results from the in vivo study were similar to the in vitro data, demonstrating the highest total-tract aNDF digestibility (70%; NDF analysis conducted with α-amylase and sodium sulfite) for cows fed the corn silage with the lowest ester- and ether-linked pCA content in the NDF fraction. 28780096 13 24 theme carbohydrate 2626:2637 arg1 moieties 2639:2646 the carbohydrate moieties 2622:2646 the carbohydrate moieties 2622:2646 In this study, digestibility of forage fiber was influenced by the linkages among lignin and the carbohydrate moieties, which vary by hybrid and species and most likely vary by the agronomic conditions under which the plant was grown. 28780096 2 25 theme detergent 485:493 arg1 ADL 503:505 ADL 503:505 ADL 503:505 The content of acid detergent lignin (ADL) and its relationship with NDF does not fully explain the observed variability in NDFD. 28780096 2 25 theme detergent 485:493 arg1 lignin 495:500 acid detergent lignin 480:500 acid detergent lignin (ADL) 480:506 The content of acid detergent lignin (ADL) and its relationship with NDF does not fully explain the observed variability in NDFD. 28780096 8 26 theme NDF 1649:1651 arg1 residues 1661:1668 both NDF and ADF residues 1644:1668 residues 1661:1668 From the in vitro study, the phenolic acid content (total pCA and FA) was highest for corn silages, and overall the content of ester- and ether-linked pCA and FA in both NDF and ADF residues were correlated with NDF digestibility parameters, reflecting the competitive effect of these linkages on digestibility. 28780096 3 27 theme cell 652:655 arg1 polysaccharides 662:676 cell wall polysaccharides 652:676 cell wall polysaccharides 652:676 The ferulic and p-coumaric acid linkages between ADL and cell wall polysaccharides, rather than the amount of ADL, might be a better predictor of NDFD. 28780096 1 28 theme linkages 346:353 arg1 composition 301:311 the chemical composition 288:311 the chemical composition of forages and specific chemical linkages 288:353 The objective of this study was to correlate in vitro and in vivo neutral detergent fiber (NDF) digestibility (NDFD) with the chemical composition of forages and specific chemical linkages, primarily ester- and ether-linked para-coumaric (pCA) and ferulic acids (FA) in forages fed to dairy cattle. 28780096 8 29 theme phenolic 1508:1515 arg1 content 1522:1528 the phenolic acid content 1504:1528 the phenolic acid content (total pCA and FA) 1504:1547 From the in vitro study, the phenolic acid content (total pCA and FA) was highest for corn silages, and overall the content of ester- and ether-linked pCA and FA in both NDF and ADF residues were correlated with NDF digestibility parameters, reflecting the competitive effect of these linkages on digestibility. 28780096 8 29 theme phenolic 1508:1515 arg1 highest 1553:1559 highest 1553:1559 highest 1553:1559 From the in vitro study, the phenolic acid content (total pCA and FA) was highest for corn silages, and overall the content of ester- and ether-linked pCA and FA in both NDF and ADF residues were correlated with NDF digestibility parameters, reflecting the competitive effect of these linkages on digestibility. 28780096 3 30 theme better 721:726 arg1 linkages 627:634 The ferulic and p-coumaric acid linkages 595:634 The ferulic and p-coumaric acid linkages between ADL and cell wall polysaccharides, rather than the amount of ADL, 595:708 The ferulic and p-coumaric acid linkages between ADL and cell wall polysaccharides, rather than the amount of ADL, might be a better predictor of NDFD. 28780096 3 30 theme better 721:726 arg1 predictor 728:736 a better predictor 719:736 a better predictor of NDFD 719:744 The ferulic and p-coumaric acid linkages between ADL and cell wall polysaccharides, rather than the amount of ADL, might be a better predictor of NDFD. 28780096 7 31 theme ADF 1386:1388 arg1 residues 1390:1397 NDF and ADF residues 1378:1397 residues 1390:1397 Intact samples and NDF and ADF residues of diet, rumen, and feces were analyzed for ester- and ether-linked pCA and FA. 28780096 7 31 theme ADF 1386:1388 arg1 rumen 1408:1412 rumen 1408:1412 rumen 1408:1412 Intact samples and NDF and ADF residues of diet, rumen, and feces were analyzed for ester- and ether-linked pCA and FA. 28780096 7 31 theme ADF 1386:1388 arg1 feces 1419:1423 feces 1419:1423 feces 1419:1423 Intact samples and NDF and ADF residues of diet, rumen, and feces were analyzed for ester- and ether-linked pCA and FA. 28780096 7 31 theme ADF 1386:1388 arg1 diet 1402:1405 diet 1402:1405 diet 1402:1405 Intact samples and NDF and ADF residues of diet, rumen, and feces were analyzed for ester- and ether-linked pCA and FA. 28780096 4 32 theme conventional 779:790 arg1 silages 814:820 conventional and brown midrib corn silages 779:820 conventional and brown midrib corn silages 779:820 Twenty-three forages, including conventional and brown midrib corn silages and grasses at various stages of maturity were incubated in vitro for measurement of 24-h and 96-h NDFD. 28780096 1 33 dep in 224:225 arg1 vivo 227:230 vivo 227:230 vivo 227:230 The objective of this study was to correlate in vitro and in vivo neutral detergent fiber (NDF) digestibility (NDFD) with the chemical composition of forages and specific chemical linkages, primarily ester- and ether-linked para-coumaric (pCA) and ferulic acids (FA) in forages fed to dairy cattle. 28780096 11 34 theme chemical 2088:2095 arg1 linkages 2097:2104 chemical linkages 2088:2104 chemical linkages 2088:2104 The lignin content of the plant residues and chemical linkages explained most of the variation in both rate and extent of NDF digestion but not uniformly among forages, ranging from 56 to 99%. 28780096 7 35 theme NDF 1378:1380 arg1 residues 1390:1397 NDF and ADF residues 1378:1397 residues 1390:1397 Intact samples and NDF and ADF residues of diet, rumen, and feces were analyzed for ester- and ether-linked pCA and FA. 28780096 7 35 theme NDF 1378:1380 arg1 rumen 1408:1412 rumen 1408:1412 rumen 1408:1412 Intact samples and NDF and ADF residues of diet, rumen, and feces were analyzed for ester- and ether-linked pCA and FA. 28780096 7 35 theme NDF 1378:1380 arg1 feces 1419:1423 feces 1419:1423 feces 1419:1423 Intact samples and NDF and ADF residues of diet, rumen, and feces were analyzed for ester- and ether-linked pCA and FA. 28780096 7 35 theme NDF 1378:1380 arg1 diet 1402:1405 diet 1402:1405 diet 1402:1405 Intact samples and NDF and ADF residues of diet, rumen, and feces were analyzed for ester- and ether-linked pCA and FA. 28780096 1 36 from ester- 366:371 arg1 forages 436:442 forages 436:442 forages fed to dairy cattle 436:462 The objective of this study was to correlate in vitro and in vivo neutral detergent fiber (NDF) digestibility (NDFD) with the chemical composition of forages and specific chemical linkages, primarily ester- and ether-linked para-coumaric (pCA) and ferulic acids (FA) in forages fed to dairy cattle. 28780096 6 37 theme iso-NDF 1344:1350 arg1 diets 1352:1356 3 iso-NDF diets 1342:1356 3 iso-NDF diets 1342:1356 To determine whether in vitro observations of ester- and ether-linked pCA and FA and digestibility were similar to in vivo observations, 3 corn silages selected for digestibility were fed to 6 ruminally fistulated cows for 3 wk in 3 iso-NDF diets. 28780096 4 38 theme maturity 855:862 arg1 stages 845:850 various stages 837:850 various stages of maturity 837:862 Twenty-three forages, including conventional and brown midrib corn silages and grasses at various stages of maturity were incubated in vitro for measurement of 24-h and 96-h NDFD. 28780096 2 39 from variability 574:584 arg1 NDFD 589:592 NDFD 589:592 NDFD 589:592 The content of acid detergent lignin (ADL) and its relationship with NDF does not fully explain the observed variability in NDFD. 28780096 12 40 dep in 2291:2292 arg1 vitro 2294:2298 vitro 2294:2298 vitro 2294:2298 The results from the in vivo study were similar to the in vitro data, demonstrating the highest total-tract aNDF digestibility (70%; NDF analysis conducted with α-amylase and sodium sulfite) for cows fed the corn silage with the lowest ester- and ether-linked pCA content in the NDF fraction. 28780096 5 41 theme detergent 988:996 arg1 ADF 1005:1007 ADF 1005:1007 ADF 1005:1007 Undigested and digested residues were analyzed for NDF, acid detergent fiber (ADF), ADL, and Klason lignin (KL); ester- and ether-linked pCA and FA were determined in these fractions. 28780096 5 41 theme detergent 988:996 arg1 fiber 998:1002 acid detergent fiber 983:1002 acid detergent fiber (ADF) 983:1008 Undigested and digested residues were analyzed for NDF, acid detergent fiber (ADF), ADL, and Klason lignin (KL); ester- and ether-linked pCA and FA were determined in these fractions. 28780096 12 42 theme NDF 2369:2371 arg1 analysis 2373:2380 NDF analysis 2369:2380 70%; NDF analysis conducted with α-amylase and sodium sulfite 2364:2424 The results from the in vivo study were similar to the in vitro data, demonstrating the highest total-tract aNDF digestibility (70%; NDF analysis conducted with α-amylase and sodium sulfite) for cows fed the corn silage with the lowest ester- and ether-linked pCA content in the NDF fraction. 28780096 13 43 theme fiber 2568:2572 arg1 digestibility 2544:2556 digestibility 2544:2556 digestibility of forage fiber 2544:2572 In this study, digestibility of forage fiber was influenced by the linkages among lignin and the carbohydrate moieties, which vary by hybrid and species and most likely vary by the agronomic conditions under which the plant was grown. 28780096 0 44 from Effect 0:5 arg1 rate 130:133 rate 130:133 rate of digestion of grass forages 130:163 Effect of lignin linkages with other plant cell wall components on in vitro and in vivo neutral detergent fiber digestibility and rate of digestion of grass forages. 28780096 0 44 from Effect 0:5 arg1 digestibility 112:124 in vitro and in vivo neutral detergent fiber digestibility 67:124 in vitro and in vivo neutral detergent fiber digestibility 67:124 Effect of lignin linkages with other plant cell wall components on in vitro and in vivo neutral detergent fiber digestibility and rate of digestion of grass forages. 28780096 8 45 dep in 1488:1489 arg1 vitro 1491:1495 vitro 1491:1495 vitro 1491:1495 From the in vitro study, the phenolic acid content (total pCA and FA) was highest for corn silages, and overall the content of ester- and ether-linked pCA and FA in both NDF and ADF residues were correlated with NDF digestibility parameters, reflecting the competitive effect of these linkages on digestibility. 28780096 6 46 theme ether-linked 1168:1179 arg1 pCA 1181:1183 ether-linked pCA 1168:1183 ether-linked pCA 1168:1183 To determine whether in vitro observations of ester- and ether-linked pCA and FA and digestibility were similar to in vivo observations, 3 corn silages selected for digestibility were fed to 6 ruminally fistulated cows for 3 wk in 3 iso-NDF diets. 28780096 0 47 dep in 80:81 arg1 vivo 83:86 vivo 83:86 vivo 83:86 Effect of lignin linkages with other plant cell wall components on in vitro and in vivo neutral detergent fiber digestibility and rate of digestion of grass forages. 28780096 12 48 theme corn 2444:2447 arg1 silage 2449:2454 the corn silage 2440:2454 the corn silage with the lowest ester- and ether-linked pCA content in the NDF fraction 2440:2526 The results from the in vivo study were similar to the in vitro data, demonstrating the highest total-tract aNDF digestibility (70%; NDF analysis conducted with α-amylase and sodium sulfite) for cows fed the corn silage with the lowest ester- and ether-linked pCA content in the NDF fraction. 28780096 11 49 theme digestion 2169:2177 arg1 rate 2146:2149 rate 2146:2149 rate 2146:2149 The lignin content of the plant residues and chemical linkages explained most of the variation in both rate and extent of NDF digestion but not uniformly among forages, ranging from 56 to 99%. 28780096 11 49 theme digestion 2169:2177 arg1 extent 2155:2160 extent 2155:2160 extent 2155:2160 The lignin content of the plant residues and chemical linkages explained most of the variation in both rate and extent of NDF digestion but not uniformly among forages, ranging from 56 to 99%. 28780096 10 50 theme esterified 1903:1912 arg1 FA 1914:1915 esterified FA 1903:1915 esterified FA 1903:1915 Overall, esterified FA and esterified pCA were negatively correlated with all of the measured fiber fractions on both a dry matter and an NDF basis. 28780096 0 51 theme in 80:81 arg1 digestibility 112:124 in vitro and in vivo neutral detergent fiber digestibility 67:124 in vitro and in vivo neutral detergent fiber digestibility 67:124 Effect of lignin linkages with other plant cell wall components on in vitro and in vivo neutral detergent fiber digestibility and rate of digestion of grass forages. 28780096 0 52 theme other 31:35 arg1 components 53:62 other plant cell wall components 31:62 other plant cell wall components 31:62 Effect of lignin linkages with other plant cell wall components on in vitro and in vivo neutral detergent fiber digestibility and rate of digestion of grass forages. 28780096 6 53 from wk 1336:1337 arg1 diets 1352:1356 3 iso-NDF diets 1342:1356 3 iso-NDF diets 1342:1356 To determine whether in vitro observations of ester- and ether-linked pCA and FA and digestibility were similar to in vivo observations, 3 corn silages selected for digestibility were fed to 6 ruminally fistulated cows for 3 wk in 3 iso-NDF diets. 28780096 8 54 link ether-linked 1617:1628 arg1 pCA 1630:1632 ether-linked pCA 1617:1632 ether-linked pCA 1617:1632 From the in vitro study, the phenolic acid content (total pCA and FA) was highest for corn silages, and overall the content of ester- and ether-linked pCA and FA in both NDF and ADF residues were correlated with NDF digestibility parameters, reflecting the competitive effect of these linkages on digestibility. 28780096 8 55 theme linkages 1764:1771 arg1 effect 1748:1753 the competitive effect 1732:1753 the competitive effect of these linkages on digestibility 1732:1788 From the in vitro study, the phenolic acid content (total pCA and FA) was highest for corn silages, and overall the content of ester- and ether-linked pCA and FA in both NDF and ADF residues were correlated with NDF digestibility parameters, reflecting the competitive effect of these linkages on digestibility. 28780096 1 56 theme fiber 250:254 arg1 NDFD 277:280 NDFD 277:280 NDFD 277:280 The objective of this study was to correlate in vitro and in vivo neutral detergent fiber (NDF) digestibility (NDFD) with the chemical composition of forages and specific chemical linkages, primarily ester- and ether-linked para-coumaric (pCA) and ferulic acids (FA) in forages fed to dairy cattle. 28780096 1 56 theme fiber 250:254 arg1 digestibility 262:274 in vitro and in vivo neutral detergent fiber (NDF) digestibility 211:274 in vitro and in vivo neutral detergent fiber (NDF) digestibility (NDFD) 211:281 The objective of this study was to correlate in vitro and in vivo neutral detergent fiber (NDF) digestibility (NDFD) with the chemical composition of forages and specific chemical linkages, primarily ester- and ether-linked para-coumaric (pCA) and ferulic acids (FA) in forages fed to dairy cattle. 28780096 2 57 theme observed 565:572 arg1 variability 574:584 the observed variability 561:584 the observed variability in NDFD 561:592 The content of acid detergent lignin (ADL) and its relationship with NDF does not fully explain the observed variability in NDFD. 28780096 8 58 theme ether-linked 1617:1628 arg1 pCA 1630:1632 ether-linked pCA 1617:1632 ether-linked pCA 1617:1632 From the in vitro study, the phenolic acid content (total pCA and FA) was highest for corn silages, and overall the content of ester- and ether-linked pCA and FA in both NDF and ADF residues were correlated with NDF digestibility parameters, reflecting the competitive effect of these linkages on digestibility. 28780096 8 59 theme corn 1565:1568 arg1 silages 1570:1576 corn silages 1565:1576 corn silages 1565:1576 From the in vitro study, the phenolic acid content (total pCA and FA) was highest for corn silages, and overall the content of ester- and ether-linked pCA and FA in both NDF and ADF residues were correlated with NDF digestibility parameters, reflecting the competitive effect of these linkages on digestibility. 28780096 4 60 theme 24-h 907:910 arg1 NDFD 921:924 24-h and 96-h NDFD 907:924 24-h and 96-h NDFD 907:924 Twenty-three forages, including conventional and brown midrib corn silages and grasses at various stages of maturity were incubated in vitro for measurement of 24-h and 96-h NDFD. 28780096 6 61 link ether-linked 1168:1179 arg1 pCA 1181:1183 ether-linked pCA 1168:1183 ether-linked pCA 1168:1183 To determine whether in vitro observations of ester- and ether-linked pCA and FA and digestibility were similar to in vivo observations, 3 corn silages selected for digestibility were fed to 6 ruminally fistulated cows for 3 wk in 3 iso-NDF diets. 28780096 0 62 theme lignin 10:15 arg1 linkages 17:24 lignin linkages 10:24 lignin linkages 10:24 Effect of lignin linkages with other plant cell wall components on in vitro and in vivo neutral detergent fiber digestibility and rate of digestion of grass forages. 28780096 1 63 theme detergent 240:248 arg1 NDFD 277:280 NDFD 277:280 NDFD 277:280 The objective of this study was to correlate in vitro and in vivo neutral detergent fiber (NDF) digestibility (NDFD) with the chemical composition of forages and specific chemical linkages, primarily ester- and ether-linked para-coumaric (pCA) and ferulic acids (FA) in forages fed to dairy cattle. 28780096 1 63 theme detergent 240:248 arg1 digestibility 262:274 in vitro and in vivo neutral detergent fiber (NDF) digestibility 211:274 in vitro and in vivo neutral detergent fiber (NDF) digestibility (NDFD) 211:281 The objective of this study was to correlate in vitro and in vivo neutral detergent fiber (NDF) digestibility (NDFD) with the chemical composition of forages and specific chemical linkages, primarily ester- and ether-linked para-coumaric (pCA) and ferulic acids (FA) in forages fed to dairy cattle. 28780096 13 64 theme agronomic 2710:2718 arg1 conditions 2720:2729 the agronomic conditions 2706:2729 the agronomic conditions under which the plant was grown 2706:2761 In this study, digestibility of forage fiber was influenced by the linkages among lignin and the carbohydrate moieties, which vary by hybrid and species and most likely vary by the agronomic conditions under which the plant was grown. 28780096 8 65 theme competitive 1736:1746 arg1 effect 1748:1753 the competitive effect 1732:1753 the competitive effect of these linkages on digestibility 1732:1788 From the in vitro study, the phenolic acid content (total pCA and FA) was highest for corn silages, and overall the content of ester- and ether-linked pCA and FA in both NDF and ADF residues were correlated with NDF digestibility parameters, reflecting the competitive effect of these linkages on digestibility. 28780096 11 66 dep 99 2231:2232 arg1 to 2228:2229 to 2228:2229 to 2228:2229 The lignin content of the plant residues and chemical linkages explained most of the variation in both rate and extent of NDF digestion but not uniformly among forages, ranging from 56 to 99%. 28780096 8 67 theme NDF 1691:1693 arg1 parameters 1709:1718 NDF digestibility parameters 1691:1718 NDF digestibility parameters 1691:1718 From the in vitro study, the phenolic acid content (total pCA and FA) was highest for corn silages, and overall the content of ester- and ether-linked pCA and FA in both NDF and ADF residues were correlated with NDF digestibility parameters, reflecting the competitive effect of these linkages on digestibility. 28780096 12 68 theme in 2291:2292 arg1 data 2300:2303 the in vitro data 2287:2303 the in vitro data 2287:2303 The results from the in vivo study were similar to the in vitro data, demonstrating the highest total-tract aNDF digestibility (70%; NDF analysis conducted with α-amylase and sodium sulfite) for cows fed the corn silage with the lowest ester- and ether-linked pCA content in the NDF fraction. 28780096 0 69 theme wall 48:51 arg1 components 53:62 other plant cell wall components 31:62 other plant cell wall components 31:62 Effect of lignin linkages with other plant cell wall components on in vitro and in vivo neutral detergent fiber digestibility and rate of digestion of grass forages. 28780096 9 70 theme ether-linked 1851:1862 arg1 acid 1872:1875 ether-linked ferulic acid 1851:1875 ether-linked ferulic acid on an NDF basis 1851:1891 Also, Klason lignin and ADL were negatively correlated with ether-linked ferulic acid on an NDF basis. 28780096 0 71 theme plant 37:41 arg1 components 53:62 other plant cell wall components 31:62 other plant cell wall components 31:62 Effect of lignin linkages with other plant cell wall components on in vitro and in vivo neutral detergent fiber digestibility and rate of digestion of grass forages. 28780096 10 72 from fractions 1994:2002 arg1 matter 2018:2023 a dry matter 2012:2023 a dry matter 2012:2023 Overall, esterified FA and esterified pCA were negatively correlated with all of the measured fiber fractions on both a dry matter and an NDF basis. 28780096 10 72 from fractions 1994:2002 arg1 basis 2036:2040 an NDF basis 2029:2040 an NDF basis 2029:2040 Overall, esterified FA and esterified pCA were negatively correlated with all of the measured fiber fractions on both a dry matter and an NDF basis. 28780096 0 73 with Effect 0:5 arg1 components 53:62 other plant cell wall components 31:62 other plant cell wall components 31:62 Effect of lignin linkages with other plant cell wall components on in vitro and in vivo neutral detergent fiber digestibility and rate of digestion of grass forages. 28780096 12 74 theme NDF 2515:2517 arg1 fraction 2519:2526 the NDF fraction 2511:2526 the NDF fraction 2511:2526 The results from the in vivo study were similar to the in vitro data, demonstrating the highest total-tract aNDF digestibility (70%; NDF analysis conducted with α-amylase and sodium sulfite) for cows fed the corn silage with the lowest ester- and ether-linked pCA content in the NDF fraction. 28780096 8 75 theme total 1531:1535 arg1 pCA 1537:1539 total pCA 1531:1539 total pCA 1531:1539 From the in vitro study, the phenolic acid content (total pCA and FA) was highest for corn silages, and overall the content of ester- and ether-linked pCA and FA in both NDF and ADF residues were correlated with NDF digestibility parameters, reflecting the competitive effect of these linkages on digestibility. 28780096 1 76 theme study 188:192 arg1 objective 170:178 The objective 166:178 The objective of this study 166:192 The objective of this study was to correlate in vitro and in vivo neutral detergent fiber (NDF) digestibility (NDFD) with the chemical composition of forages and specific chemical linkages, primarily ester- and ether-linked para-coumaric (pCA) and ferulic acids (FA) in forages fed to dairy cattle. 28780096 1 76 theme study 188:192 arg1 ester- 366:371 ester- 366:371 ester- 366:371 The objective of this study was to correlate in vitro and in vivo neutral detergent fiber (NDF) digestibility (NDFD) with the chemical composition of forages and specific chemical linkages, primarily ester- and ether-linked para-coumaric (pCA) and ferulic acids (FA) in forages fed to dairy cattle. 28780096 8 77 dep content 1522:1528 arg1 FA 1545:1546 FA 1545:1546 FA 1545:1546 From the in vitro study, the phenolic acid content (total pCA and FA) was highest for corn silages, and overall the content of ester- and ether-linked pCA and FA in both NDF and ADF residues were correlated with NDF digestibility parameters, reflecting the competitive effect of these linkages on digestibility. 28780096 8 77 dep content 1522:1528 arg1 pCA 1537:1539 total pCA 1531:1539 total pCA 1531:1539 From the in vitro study, the phenolic acid content (total pCA and FA) was highest for corn silages, and overall the content of ester- and ether-linked pCA and FA in both NDF and ADF residues were correlated with NDF digestibility parameters, reflecting the competitive effect of these linkages on digestibility. 28780096 13 78 dep fiber 2568:2572 arg1 forage 2561:2566 forage 2561:2566 forage 2561:2566 In this study, digestibility of forage fiber was influenced by the linkages among lignin and the carbohydrate moieties, which vary by hybrid and species and most likely vary by the agronomic conditions under which the plant was grown. 28780096 4 79 from stages 845:850 arg1 grasses 826:832 grasses 826:832 grasses at various stages of maturity 826:862 Twenty-three forages, including conventional and brown midrib corn silages and grasses at various stages of maturity were incubated in vitro for measurement of 24-h and 96-h NDFD. 28780096 4 79 from stages 845:850 arg1 forages 760:766 Twenty-three forages 747:766 Twenty-three forages 747:766 Twenty-three forages, including conventional and brown midrib corn silages and grasses at various stages of maturity were incubated in vitro for measurement of 24-h and 96-h NDFD. 28780096 4 79 from stages 845:850 arg1 silages 814:820 conventional and brown midrib corn silages 779:820 conventional and brown midrib corn silages 779:820 Twenty-three forages, including conventional and brown midrib corn silages and grasses at various stages of maturity were incubated in vitro for measurement of 24-h and 96-h NDFD. 28780096 4 80 theme 96-h 916:919 arg1 NDFD 921:924 24-h and 96-h NDFD 907:924 24-h and 96-h NDFD 907:924 Twenty-three forages, including conventional and brown midrib corn silages and grasses at various stages of maturity were incubated in vitro for measurement of 24-h and 96-h NDFD. 28780096 6 81 theme FA 1189:1190 arg1 observations 1141:1152 in vitro observations 1132:1152 in vitro observations of ester- and ether-linked pCA and FA and digestibility 1132:1208 To determine whether in vitro observations of ester- and ether-linked pCA and FA and digestibility were similar to in vivo observations, 3 corn silages selected for digestibility were fed to 6 ruminally fistulated cows for 3 wk in 3 iso-NDF diets. 28780096 0 82 theme grass 151:155 arg1 forages 157:163 grass forages 151:163 grass forages 151:163 Effect of lignin linkages with other plant cell wall components on in vitro and in vivo neutral detergent fiber digestibility and rate of digestion of grass forages. 28780096 12 83 theme pCA 2496:2498 arg1 content 2500:2506 ether-linked pCA content 2483:2506 ether-linked pCA content 2483:2506 The results from the in vivo study were similar to the in vitro data, demonstrating the highest total-tract aNDF digestibility (70%; NDF analysis conducted with α-amylase and sodium sulfite) for cows fed the corn silage with the lowest ester- and ether-linked pCA content in the NDF fraction. 28780096 2 84 with content 469:475 arg1 NDF 534:536 NDF 534:536 NDF 534:536 The content of acid detergent lignin (ADL) and its relationship with NDF does not fully explain the observed variability in NDFD. 28780096 1 85 theme in 211:212 arg1 NDFD 277:280 NDFD 277:280 NDFD 277:280 The objective of this study was to correlate in vitro and in vivo neutral detergent fiber (NDF) digestibility (NDFD) with the chemical composition of forages and specific chemical linkages, primarily ester- and ether-linked para-coumaric (pCA) and ferulic acids (FA) in forages fed to dairy cattle. 28780096 1 85 theme in 211:212 arg1 digestibility 262:274 in vitro and in vivo neutral detergent fiber (NDF) digestibility 211:274 in vitro and in vivo neutral detergent fiber (NDF) digestibility (NDFD) 211:281 The objective of this study was to correlate in vitro and in vivo neutral detergent fiber (NDF) digestibility (NDFD) with the chemical composition of forages and specific chemical linkages, primarily ester- and ether-linked para-coumaric (pCA) and ferulic acids (FA) in forages fed to dairy cattle. 28780096 9 86 from acid 1872:1875 arg1 basis 1887:1891 an NDF basis 1880:1891 an NDF basis 1880:1891 Also, Klason lignin and ADL were negatively correlated with ether-linked ferulic acid on an NDF basis. 28780096 1 87 theme ether-linked 377:388 arg1 FA 429:430 FA 429:430 FA 429:430 The objective of this study was to correlate in vitro and in vivo neutral detergent fiber (NDF) digestibility (NDFD) with the chemical composition of forages and specific chemical linkages, primarily ester- and ether-linked para-coumaric (pCA) and ferulic acids (FA) in forages fed to dairy cattle. 28780096 1 87 theme ether-linked 377:388 arg1 acids 422:426 ether-linked para-coumaric (pCA) and ferulic acids 377:426 ether-linked para-coumaric (pCA) and ferulic acids (FA) 377:431 The objective of this study was to correlate in vitro and in vivo neutral detergent fiber (NDF) digestibility (NDFD) with the chemical composition of forages and specific chemical linkages, primarily ester- and ether-linked para-coumaric (pCA) and ferulic acids (FA) in forages fed to dairy cattle. 28780096 6 88 theme corn 1250:1253 arg1 silages 1255:1261 3 corn silages 1248:1261 3 corn silages selected for digestibility 1248:1288 To determine whether in vitro observations of ester- and ether-linked pCA and FA and digestibility were similar to in vivo observations, 3 corn silages selected for digestibility were fed to 6 ruminally fistulated cows for 3 wk in 3 iso-NDF diets. 28780096 2 89 theme lignin 495:500 arg1 relationship 516:527 its relationship 512:527 its relationship with NDF 512:536 The content of acid detergent lignin (ADL) and its relationship with NDF does not fully explain the observed variability in NDFD. 28780096 2 89 theme lignin 495:500 arg1 content 469:475 The content 465:475 The content of acid detergent lignin (ADL) 465:506 The content of acid detergent lignin (ADL) and its relationship with NDF does not fully explain the observed variability in NDFD. 28780096 3 90 theme acid 622:625 arg1 linkages 627:634 The ferulic and p-coumaric acid linkages 595:634 The ferulic and p-coumaric acid linkages between ADL and cell wall polysaccharides, rather than the amount of ADL, 595:708 The ferulic and p-coumaric acid linkages between ADL and cell wall polysaccharides, rather than the amount of ADL, might be a better predictor of NDFD. 28780096 3 90 theme acid 622:625 arg1 predictor 728:736 a better predictor 719:736 a better predictor of NDFD 719:744 The ferulic and p-coumaric acid linkages between ADL and cell wall polysaccharides, rather than the amount of ADL, might be a better predictor of NDFD. 28780096 12 91 dep % 2366:2366 arg1 analysis 2373:2380 NDF analysis 2369:2380 70%; NDF analysis conducted with α-amylase and sodium sulfite 2364:2424 The results from the in vivo study were similar to the in vitro data, demonstrating the highest total-tract aNDF digestibility (70%; NDF analysis conducted with α-amylase and sodium sulfite) for cows fed the corn silage with the lowest ester- and ether-linked pCA content in the NDF fraction. 28780096 12 92 theme aNDF 2344:2347 arg1 digestibility 2349:2361 the highest total-tract aNDF digestibility 2320:2361 the highest total-tract aNDF digestibility (70%; NDF analysis conducted with α-amylase and sodium sulfite) 2320:2425 The results from the in vivo study were similar to the in vitro data, demonstrating the highest total-tract aNDF digestibility (70%; NDF analysis conducted with α-amylase and sodium sulfite) for cows fed the corn silage with the lowest ester- and ether-linked pCA content in the NDF fraction. 28780096 9 93 theme ferulic 1864:1870 arg1 acid 1872:1875 ether-linked ferulic acid 1851:1875 ether-linked ferulic acid on an NDF basis 1851:1891 Also, Klason lignin and ADL were negatively correlated with ether-linked ferulic acid on an NDF basis. 28780096 8 94 theme ester- 1606:1611 arg1 content 1595:1601 the content 1591:1601 the content of ester- and ether-linked pCA and FA in both NDF and ADF residues 1591:1668 From the in vitro study, the phenolic acid content (total pCA and FA) was highest for corn silages, and overall the content of ester- and ether-linked pCA and FA in both NDF and ADF residues were correlated with NDF digestibility parameters, reflecting the competitive effect of these linkages on digestibility. 28780096 7 95 theme rumen 1408:1412 arg1 residues 1390:1397 NDF and ADF residues 1378:1397 residues 1390:1397 Intact samples and NDF and ADF residues of diet, rumen, and feces were analyzed for ester- and ether-linked pCA and FA. 28780096 7 95 theme rumen 1408:1412 arg1 samples 1366:1372 Intact samples 1359:1372 Intact samples 1359:1372 Intact samples and NDF and ADF residues of diet, rumen, and feces were analyzed for ester- and ether-linked pCA and FA. 28780096 7 95 theme rumen 1408:1412 arg1 rumen 1408:1412 rumen 1408:1412 rumen 1408:1412 Intact samples and NDF and ADF residues of diet, rumen, and feces were analyzed for ester- and ether-linked pCA and FA. 28780096 7 95 theme rumen 1408:1412 arg1 feces 1419:1423 feces 1419:1423 feces 1419:1423 Intact samples and NDF and ADF residues of diet, rumen, and feces were analyzed for ester- and ether-linked pCA and FA. 28780096 7 95 theme rumen 1408:1412 arg1 diet 1402:1405 diet 1402:1405 diet 1402:1405 Intact samples and NDF and ADF residues of diet, rumen, and feces were analyzed for ester- and ether-linked pCA and FA. 28780096 10 96 theme measured 1979:1986 arg1 fractions 1994:2002 the measured fiber fractions 1975:2002 the measured fiber fractions on both a dry matter and an NDF basis 1975:2040 Overall, esterified FA and esterified pCA were negatively correlated with all of the measured fiber fractions on both a dry matter and an NDF basis. 28780096 0 97 theme detergent 96:104 arg1 digestibility 112:124 in vitro and in vivo neutral detergent fiber digestibility 67:124 in vitro and in vivo neutral detergent fiber digestibility 67:124 Effect of lignin linkages with other plant cell wall components on in vitro and in vivo neutral detergent fiber digestibility and rate of digestion of grass forages. 28780096 1 98 theme ferulic 414:420 arg1 FA 429:430 FA 429:430 FA 429:430 The objective of this study was to correlate in vitro and in vivo neutral detergent fiber (NDF) digestibility (NDFD) with the chemical composition of forages and specific chemical linkages, primarily ester- and ether-linked para-coumaric (pCA) and ferulic acids (FA) in forages fed to dairy cattle. 28780096 1 98 theme ferulic 414:420 arg1 acids 422:426 ether-linked para-coumaric (pCA) and ferulic acids 377:426 ether-linked para-coumaric (pCA) and ferulic acids (FA) 377:431 The objective of this study was to correlate in vitro and in vivo neutral detergent fiber (NDF) digestibility (NDFD) with the chemical composition of forages and specific chemical linkages, primarily ester- and ether-linked para-coumaric (pCA) and ferulic acids (FA) in forages fed to dairy cattle. 28780096 6 99 theme fistulated 1314:1323 arg1 cows 1325:1328 6 ruminally fistulated cows 1302:1328 6 ruminally fistulated cows 1302:1328 To determine whether in vitro observations of ester- and ether-linked pCA and FA and digestibility were similar to in vivo observations, 3 corn silages selected for digestibility were fed to 6 ruminally fistulated cows for 3 wk in 3 iso-NDF diets. 28780096 7 100 theme diet 1402:1405 arg1 residues 1390:1397 NDF and ADF residues 1378:1397 residues 1390:1397 Intact samples and NDF and ADF residues of diet, rumen, and feces were analyzed for ester- and ether-linked pCA and FA. 28780096 7 100 theme diet 1402:1405 arg1 samples 1366:1372 Intact samples 1359:1372 Intact samples 1359:1372 Intact samples and NDF and ADF residues of diet, rumen, and feces were analyzed for ester- and ether-linked pCA and FA. 28780096 7 100 theme diet 1402:1405 arg1 rumen 1408:1412 rumen 1408:1412 rumen 1408:1412 Intact samples and NDF and ADF residues of diet, rumen, and feces were analyzed for ester- and ether-linked pCA and FA. 28780096 7 100 theme diet 1402:1405 arg1 feces 1419:1423 feces 1419:1423 feces 1419:1423 Intact samples and NDF and ADF residues of diet, rumen, and feces were analyzed for ester- and ether-linked pCA and FA. 28780096 7 100 theme diet 1402:1405 arg1 diet 1402:1405 diet 1402:1405 diet 1402:1405 Intact samples and NDF and ADF residues of diet, rumen, and feces were analyzed for ester- and ether-linked pCA and FA. 28780096 10 101 theme dry 2014:2016 arg1 matter 2018:2023 a dry matter 2012:2023 a dry matter 2012:2023 Overall, esterified FA and esterified pCA were negatively correlated with all of the measured fiber fractions on both a dry matter and an NDF basis. 28780096 9 102 theme NDF 1883:1885 arg1 basis 1887:1891 an NDF basis 1880:1891 an NDF basis 1880:1891 Also, Klason lignin and ADL were negatively correlated with ether-linked ferulic acid on an NDF basis. 28780096 2 103 with relationship 516:527 arg1 NDF 534:536 NDF 534:536 NDF 534:536 The content of acid detergent lignin (ADL) and its relationship with NDF does not fully explain the observed variability in NDFD. 28780096 6 104 dep in 1132:1133 arg1 vitro 1135:1139 vitro 1135:1139 vitro 1135:1139 To determine whether in vitro observations of ester- and ether-linked pCA and FA and digestibility were similar to in vivo observations, 3 corn silages selected for digestibility were fed to 6 ruminally fistulated cows for 3 wk in 3 iso-NDF diets. 28780096 4 105 theme midrib 802:807 arg1 silages 814:820 conventional and brown midrib corn silages 779:820 conventional and brown midrib corn silages 779:820 Twenty-three forages, including conventional and brown midrib corn silages and grasses at various stages of maturity were incubated in vitro for measurement of 24-h and 96-h NDFD. 28780096 1 106 theme chemical 337:344 arg1 linkages 346:353 specific chemical linkages 328:353 specific chemical linkages 328:353 The objective of this study was to correlate in vitro and in vivo neutral detergent fiber (NDF) digestibility (NDFD) with the chemical composition of forages and specific chemical linkages, primarily ester- and ether-linked para-coumaric (pCA) and ferulic acids (FA) in forages fed to dairy cattle. 28780096 2 107 theme acid 480:483 arg1 ADL 503:505 ADL 503:505 ADL 503:505 The content of acid detergent lignin (ADL) and its relationship with NDF does not fully explain the observed variability in NDFD. 28780096 2 107 theme acid 480:483 arg1 lignin 495:500 acid detergent lignin 480:500 acid detergent lignin (ADL) 480:506 The content of acid detergent lignin (ADL) and its relationship with NDF does not fully explain the observed variability in NDFD. 28780096 3 108 theme wall 657:660 arg1 polysaccharides 662:676 cell wall polysaccharides 652:676 cell wall polysaccharides 652:676 The ferulic and p-coumaric acid linkages between ADL and cell wall polysaccharides, rather than the amount of ADL, might be a better predictor of NDFD. 28780096 0 109 theme digestion 138:146 arg1 rate 130:133 rate 130:133 rate of digestion of grass forages 130:163 Effect of lignin linkages with other plant cell wall components on in vitro and in vivo neutral detergent fiber digestibility and rate of digestion of grass forages. 28780096 0 109 theme digestion 138:146 arg1 digestibility 112:124 in vitro and in vivo neutral detergent fiber digestibility 67:124 in vitro and in vivo neutral detergent fiber digestibility 67:124 Effect of lignin linkages with other plant cell wall components on in vitro and in vivo neutral detergent fiber digestibility and rate of digestion of grass forages. 28780096 12 110 link ether-linked 2483:2494 arg1 content 2500:2506 ether-linked pCA content 2483:2506 ether-linked pCA content 2483:2506 The results from the in vivo study were similar to the in vitro data, demonstrating the highest total-tract aNDF digestibility (70%; NDF analysis conducted with α-amylase and sodium sulfite) for cows fed the corn silage with the lowest ester- and ether-linked pCA content in the NDF fraction. 28780096 1 111 dep in 211:212 arg1 vitro 214:218 vitro 214:218 vitro 214:218 The objective of this study was to correlate in vitro and in vivo neutral detergent fiber (NDF) digestibility (NDFD) with the chemical composition of forages and specific chemical linkages, primarily ester- and ether-linked para-coumaric (pCA) and ferulic acids (FA) in forages fed to dairy cattle. 28780096 12 112 theme in 2257:2258 arg1 study 2265:2269 the in vivo study 2253:2269 the in vivo study 2253:2269 The results from the in vivo study were similar to the in vitro data, demonstrating the highest total-tract aNDF digestibility (70%; NDF analysis conducted with α-amylase and sodium sulfite) for cows fed the corn silage with the lowest ester- and ether-linked pCA content in the NDF fraction. 28780096 1 113 theme in 224:225 arg1 NDFD 277:280 NDFD 277:280 NDFD 277:280 The objective of this study was to correlate in vitro and in vivo neutral detergent fiber (NDF) digestibility (NDFD) with the chemical composition of forages and specific chemical linkages, primarily ester- and ether-linked para-coumaric (pCA) and ferulic acids (FA) in forages fed to dairy cattle. 28780096 1 113 theme in 224:225 arg1 digestibility 262:274 in vitro and in vivo neutral detergent fiber (NDF) digestibility 211:274 in vitro and in vivo neutral detergent fiber (NDF) digestibility (NDFD) 211:281 The objective of this study was to correlate in vitro and in vivo neutral detergent fiber (NDF) digestibility (NDFD) with the chemical composition of forages and specific chemical linkages, primarily ester- and ether-linked para-coumaric (pCA) and ferulic acids (FA) in forages fed to dairy cattle. 28780096 8 114 theme ADF 1657:1659 arg1 residues 1661:1668 both NDF and ADF residues 1644:1668 residues 1661:1668 From the in vitro study, the phenolic acid content (total pCA and FA) was highest for corn silages, and overall the content of ester- and ether-linked pCA and FA in both NDF and ADF residues were correlated with NDF digestibility parameters, reflecting the competitive effect of these linkages on digestibility. 28780096 8 115 theme acid 1517:1520 arg1 content 1522:1528 the phenolic acid content 1504:1528 the phenolic acid content (total pCA and FA) 1504:1547 From the in vitro study, the phenolic acid content (total pCA and FA) was highest for corn silages, and overall the content of ester- and ether-linked pCA and FA in both NDF and ADF residues were correlated with NDF digestibility parameters, reflecting the competitive effect of these linkages on digestibility. 28780096 8 115 theme acid 1517:1520 arg1 highest 1553:1559 highest 1553:1559 highest 1553:1559 From the in vitro study, the phenolic acid content (total pCA and FA) was highest for corn silages, and overall the content of ester- and ether-linked pCA and FA in both NDF and ADF residues were correlated with NDF digestibility parameters, reflecting the competitive effect of these linkages on digestibility. 28780096 12 116 from study 2265:2269 arg1 similar 2276:2282 similar 2276:2282 similar 2276:2282 The results from the in vivo study were similar to the in vitro data, demonstrating the highest total-tract aNDF digestibility (70%; NDF analysis conducted with α-amylase and sodium sulfite) for cows fed the corn silage with the lowest ester- and ether-linked pCA content in the NDF fraction. 28780096 12 116 from study 2265:2269 arg1 results 2240:2246 The results 2236:2246 The results from the in vivo study 2236:2269 The results from the in vivo study were similar to the in vitro data, demonstrating the highest total-tract aNDF digestibility (70%; NDF analysis conducted with α-amylase and sodium sulfite) for cows fed the corn silage with the lowest ester- and ether-linked pCA content in the NDF fraction. 28780096 12 116 from study 2265:2269 arg1 demonstrating 2306:2318 demonstrating 2306:2318 demonstrating the highest total-tract aNDF digestibility (70%; NDF analysis conducted with α-amylase and sodium sulfite) for cows fed the corn silage with the lowest ester- and ether-linked pCA content in the NDF fraction 2306:2526 The results from the in vivo study were similar to the in vitro data, demonstrating the highest total-tract aNDF digestibility (70%; NDF analysis conducted with α-amylase and sodium sulfite) for cows fed the corn silage with the lowest ester- and ether-linked pCA content in the NDF fraction. 28780096 7 117 theme Intact 1359:1364 arg1 samples 1366:1372 Intact samples 1359:1372 Intact samples 1359:1372 Intact samples and NDF and ADF residues of diet, rumen, and feces were analyzed for ester- and ether-linked pCA and FA. 28780096 4 118 theme various 837:843 arg1 stages 845:850 various stages 837:850 various stages of maturity 837:862 Twenty-three forages, including conventional and brown midrib corn silages and grasses at various stages of maturity were incubated in vitro for measurement of 24-h and 96-h NDFD. 28780096 11 119 theme lignin 2047:2052 arg1 content 2054:2060 The lignin content 2043:2060 The lignin content of the plant residues 2043:2082 The lignin content of the plant residues and chemical linkages explained most of the variation in both rate and extent of NDF digestion but not uniformly among forages, ranging from 56 to 99%. 28780096 0 120 theme in 67:68 arg1 digestibility 112:124 in vitro and in vivo neutral detergent fiber digestibility 67:124 in vitro and in vivo neutral detergent fiber digestibility 67:124 Effect of lignin linkages with other plant cell wall components on in vitro and in vivo neutral detergent fiber digestibility and rate of digestion of grass forages. 28780096 5 121 theme acid 983:986 arg1 ADF 1005:1007 ADF 1005:1007 ADF 1005:1007 Undigested and digested residues were analyzed for NDF, acid detergent fiber (ADF), ADL, and Klason lignin (KL); ester- and ether-linked pCA and FA were determined in these fractions. 28780096 5 121 theme acid 983:986 arg1 fiber 998:1002 acid detergent fiber 983:1002 acid detergent fiber (ADF) 983:1008 Undigested and digested residues were analyzed for NDF, acid detergent fiber (ADF), ADL, and Klason lignin (KL); ester- and ether-linked pCA and FA were determined in these fractions. 28780096 10 122 theme esterified 1921:1930 arg1 pCA 1932:1934 esterified pCA 1921:1934 esterified pCA 1921:1934 Overall, esterified FA and esterified pCA were negatively correlated with all of the measured fiber fractions on both a dry matter and an NDF basis. 28780096 1 123 theme forages 316:322 arg1 composition 301:311 the chemical composition 288:311 the chemical composition of forages and specific chemical linkages 288:353 The objective of this study was to correlate in vitro and in vivo neutral detergent fiber (NDF) digestibility (NDFD) with the chemical composition of forages and specific chemical linkages, primarily ester- and ether-linked para-coumaric (pCA) and ferulic acids (FA) in forages fed to dairy cattle. 28780096 6 124 theme pCA 1181:1183 arg1 observations 1141:1152 in vitro observations 1132:1152 in vitro observations of ester- and ether-linked pCA and FA and digestibility 1132:1208 To determine whether in vitro observations of ester- and ether-linked pCA and FA and digestibility were similar to in vivo observations, 3 corn silages selected for digestibility were fed to 6 ruminally fistulated cows for 3 wk in 3 iso-NDF diets. 28780096 12 125 from silage 2449:2454 arg1 fraction 2519:2526 the NDF fraction 2511:2526 the NDF fraction 2511:2526 The results from the in vivo study were similar to the in vitro data, demonstrating the highest total-tract aNDF digestibility (70%; NDF analysis conducted with α-amylase and sodium sulfite) for cows fed the corn silage with the lowest ester- and ether-linked pCA content in the NDF fraction. 28780096 3 126 theme NDFD 741:744 arg1 linkages 627:634 The ferulic and p-coumaric acid linkages 595:634 The ferulic and p-coumaric acid linkages between ADL and cell wall polysaccharides, rather than the amount of ADL, 595:708 The ferulic and p-coumaric acid linkages between ADL and cell wall polysaccharides, rather than the amount of ADL, might be a better predictor of NDFD. 28780096 3 126 theme NDFD 741:744 arg1 predictor 728:736 a better predictor 719:736 a better predictor of NDFD 719:744 The ferulic and p-coumaric acid linkages between ADL and cell wall polysaccharides, rather than the amount of ADL, might be a better predictor of NDFD. 28780096 11 127 theme NDF 2165:2167 arg1 digestion 2169:2177 NDF digestion 2165:2177 NDF digestion 2165:2177 The lignin content of the plant residues and chemical linkages explained most of the variation in both rate and extent of NDF digestion but not uniformly among forages, ranging from 56 to 99%. 28780096 1 128 theme dairy 451:455 arg1 cattle 457:462 dairy cattle 451:462 dairy cattle 451:462 The objective of this study was to correlate in vitro and in vivo neutral detergent fiber (NDF) digestibility (NDFD) with the chemical composition of forages and specific chemical linkages, primarily ester- and ether-linked para-coumaric (pCA) and ferulic acids (FA) in forages fed to dairy cattle. 28780096 3 129 theme ADL 705:707 arg1 ADL 705:707 ADL 705:707 ADL 705:707 The ferulic and p-coumaric acid linkages between ADL and cell wall polysaccharides, rather than the amount of ADL, might be a better predictor of NDFD. 28780096 3 129 theme ADL 705:707 arg1 amount 695:700 the amount 691:700 the amount of ADL 691:707 The ferulic and p-coumaric acid linkages between ADL and cell wall polysaccharides, rather than the amount of ADL, might be a better predictor of NDFD. 28780096 8 130 theme digestibility 1695:1707 arg1 parameters 1709:1718 NDF digestibility parameters 1691:1718 NDF digestibility parameters 1691:1718 From the in vitro study, the phenolic acid content (total pCA and FA) was highest for corn silages, and overall the content of ester- and ether-linked pCA and FA in both NDF and ADF residues were correlated with NDF digestibility parameters, reflecting the competitive effect of these linkages on digestibility. 28780096 1 131 theme chemical 292:299 arg1 composition 301:311 the chemical composition 288:311 the chemical composition of forages and specific chemical linkages 288:353 The objective of this study was to correlate in vitro and in vivo neutral detergent fiber (NDF) digestibility (NDFD) with the chemical composition of forages and specific chemical linkages, primarily ester- and ether-linked para-coumaric (pCA) and ferulic acids (FA) in forages fed to dairy cattle. 28780096 7 132 theme ether-linked 1454:1465 arg1 pCA 1467:1469 ether-linked pCA 1454:1469 ether-linked pCA 1454:1469 Intact samples and NDF and ADF residues of diet, rumen, and feces were analyzed for ester- and ether-linked pCA and FA. 28780096 12 133 theme highest 2324:2330 arg1 digestibility 2349:2361 the highest total-tract aNDF digestibility 2320:2361 the highest total-tract aNDF digestibility (70%; NDF analysis conducted with α-amylase and sodium sulfite) 2320:2425 The results from the in vivo study were similar to the in vitro data, demonstrating the highest total-tract aNDF digestibility (70%; NDF analysis conducted with α-amylase and sodium sulfite) for cows fed the corn silage with the lowest ester- and ether-linked pCA content in the NDF fraction. 28780096 8 134 from effect 1748:1753 arg1 digestibility 1776:1788 digestibility 1776:1788 digestibility 1776:1788 From the in vitro study, the phenolic acid content (total pCA and FA) was highest for corn silages, and overall the content of ester- and ether-linked pCA and FA in both NDF and ADF residues were correlated with NDF digestibility parameters, reflecting the competitive effect of these linkages on digestibility. 28780096 11 135 theme plant 2069:2073 arg1 residues 2075:2082 the plant residues 2065:2082 the plant residues 2065:2082 The lignin content of the plant residues and chemical linkages explained most of the variation in both rate and extent of NDF digestion but not uniformly among forages, ranging from 56 to 99%. 28780096 7 136 link ether-linked 1454:1465 arg1 pCA 1467:1469 ether-linked pCA 1454:1469 ether-linked pCA 1454:1469 Intact samples and NDF and ADF residues of diet, rumen, and feces were analyzed for ester- and ether-linked pCA and FA. 28780096 0 137 dep in 67:68 arg1 vitro 70:74 vitro 70:74 vitro 70:74 Effect of lignin linkages with other plant cell wall components on in vitro and in vivo neutral detergent fiber digestibility and rate of digestion of grass forages. 28780096 12 138 theme total-tract 2332:2342 arg1 digestibility 2349:2361 the highest total-tract aNDF digestibility 2320:2361 the highest total-tract aNDF digestibility (70%; NDF analysis conducted with α-amylase and sodium sulfite) 2320:2425 The results from the in vivo study were similar to the in vitro data, demonstrating the highest total-tract aNDF digestibility (70%; NDF analysis conducted with α-amylase and sodium sulfite) for cows fed the corn silage with the lowest ester- and ether-linked pCA content in the NDF fraction. 28780096 11 139 from variation 2128:2136 arg1 rate 2146:2149 rate 2146:2149 rate 2146:2149 The lignin content of the plant residues and chemical linkages explained most of the variation in both rate and extent of NDF digestion but not uniformly among forages, ranging from 56 to 99%. 28780096 11 139 from variation 2128:2136 arg1 extent 2155:2160 extent 2155:2160 extent 2155:2160 The lignin content of the plant residues and chemical linkages explained most of the variation in both rate and extent of NDF digestion but not uniformly among forages, ranging from 56 to 99%. 28780096 0 140 theme linkages 17:24 arg1 Effect 0:5 Effect 0:5 Effect of lignin linkages with other plant cell wall components on in vitro and in vivo neutral detergent fiber digestibility and rate of digestion of grass forages. 0:164 Effect of lignin linkages with other plant cell wall components on in vitro and in vivo neutral detergent fiber digestibility and rate of digestion of grass forages. 28780096 1 141 theme neutral 232:238 arg1 NDFD 277:280 NDFD 277:280 NDFD 277:280 The objective of this study was to correlate in vitro and in vivo neutral detergent fiber (NDF) digestibility (NDFD) with the chemical composition of forages and specific chemical linkages, primarily ester- and ether-linked para-coumaric (pCA) and ferulic acids (FA) in forages fed to dairy cattle. 28780096 1 141 theme neutral 232:238 arg1 digestibility 262:274 in vitro and in vivo neutral detergent fiber (NDF) digestibility 211:274 in vitro and in vivo neutral detergent fiber (NDF) digestibility (NDFD) 211:281 The objective of this study was to correlate in vitro and in vivo neutral detergent fiber (NDF) digestibility (NDFD) with the chemical composition of forages and specific chemical linkages, primarily ester- and ether-linked para-coumaric (pCA) and ferulic acids (FA) in forages fed to dairy cattle. 28780096 8 142 theme in 1488:1489 arg1 study 1497:1501 the in vitro study 1484:1501 the in vitro study 1484:1501 From the in vitro study, the phenolic acid content (total pCA and FA) was highest for corn silages, and overall the content of ester- and ether-linked pCA and FA in both NDF and ADF residues were correlated with NDF digestibility parameters, reflecting the competitive effect of these linkages on digestibility. 28780096 6 143 theme in 1226:1227 arg1 observations 1234:1245 in vivo observations 1226:1245 in vivo observations 1226:1245 To determine whether in vitro observations of ester- and ether-linked pCA and FA and digestibility were similar to in vivo observations, 3 corn silages selected for digestibility were fed to 6 ruminally fistulated cows for 3 wk in 3 iso-NDF diets. 28780096 5 144 theme Klason 1020:1025 arg1 KL 1035:1036 KL 1035:1036 KL 1035:1036 Undigested and digested residues were analyzed for NDF, acid detergent fiber (ADF), ADL, and Klason lignin (KL); ester- and ether-linked pCA and FA were determined in these fractions. 28780096 5 144 theme Klason 1020:1025 arg1 lignin 1027:1032 Klason lignin 1020:1032 Klason lignin (KL) 1020:1037 Undigested and digested residues were analyzed for NDF, acid detergent fiber (ADF), ADL, and Klason lignin (KL); ester- and ether-linked pCA and FA were determined in these fractions. 28780096 6 145 dep in 1226:1227 arg1 vivo 1229:1232 vivo 1229:1232 vivo 1229:1232 To determine whether in vitro observations of ester- and ether-linked pCA and FA and digestibility were similar to in vivo observations, 3 corn silages selected for digestibility were fed to 6 ruminally fistulated cows for 3 wk in 3 iso-NDF diets. 28780096 7 146 theme feces 1419:1423 arg1 residues 1390:1397 NDF and ADF residues 1378:1397 residues 1390:1397 Intact samples and NDF and ADF residues of diet, rumen, and feces were analyzed for ester- and ether-linked pCA and FA. 28780096 7 146 theme feces 1419:1423 arg1 samples 1366:1372 Intact samples 1359:1372 Intact samples 1359:1372 Intact samples and NDF and ADF residues of diet, rumen, and feces were analyzed for ester- and ether-linked pCA and FA. 28780096 7 146 theme feces 1419:1423 arg1 rumen 1408:1412 rumen 1408:1412 rumen 1408:1412 Intact samples and NDF and ADF residues of diet, rumen, and feces were analyzed for ester- and ether-linked pCA and FA. 28780096 7 146 theme feces 1419:1423 arg1 feces 1419:1423 feces 1419:1423 feces 1419:1423 Intact samples and NDF and ADF residues of diet, rumen, and feces were analyzed for ester- and ether-linked pCA and FA. 28780096 7 146 theme feces 1419:1423 arg1 diet 1402:1405 diet 1402:1405 diet 1402:1405 Intact samples and NDF and ADF residues of diet, rumen, and feces were analyzed for ester- and ether-linked pCA and FA. 28780096 1 147 from acids 422:426 arg1 forages 436:442 forages 436:442 forages fed to dairy cattle 436:462 The objective of this study was to correlate in vitro and in vivo neutral detergent fiber (NDF) digestibility (NDFD) with the chemical composition of forages and specific chemical linkages, primarily ester- and ether-linked para-coumaric (pCA) and ferulic acids (FA) in forages fed to dairy cattle. 28780096 6 148 theme ester- 1157:1162 arg1 observations 1141:1152 in vitro observations 1132:1152 in vitro observations of ester- and ether-linked pCA and FA and digestibility 1132:1208 To determine whether in vitro observations of ester- and ether-linked pCA and FA and digestibility were similar to in vivo observations, 3 corn silages selected for digestibility were fed to 6 ruminally fistulated cows for 3 wk in 3 iso-NDF diets. 28780096 0 149 theme cell 43:46 arg1 components 53:62 other plant cell wall components 31:62 other plant cell wall components 31:62 Effect of lignin linkages with other plant cell wall components on in vitro and in vivo neutral detergent fiber digestibility and rate of digestion of grass forages. 28780096 1 150 theme NDF 257:259 arg1 NDFD 277:280 NDFD 277:280 NDFD 277:280 The objective of this study was to correlate in vitro and in vivo neutral detergent fiber (NDF) digestibility (NDFD) with the chemical composition of forages and specific chemical linkages, primarily ester- and ether-linked para-coumaric (pCA) and ferulic acids (FA) in forages fed to dairy cattle. 28780096 1 150 theme NDF 257:259 arg1 digestibility 262:274 in vitro and in vivo neutral detergent fiber (NDF) digestibility 211:274 in vitro and in vivo neutral detergent fiber (NDF) digestibility (NDFD) 211:281 The objective of this study was to correlate in vitro and in vivo neutral detergent fiber (NDF) digestibility (NDFD) with the chemical composition of forages and specific chemical linkages, primarily ester- and ether-linked para-coumaric (pCA) and ferulic acids (FA) in forages fed to dairy cattle. 28780096 12 151 with silage 2449:2454 arg1 ester- 2472:2477 the lowest ester- 2461:2477 the lowest ester- 2461:2477 The results from the in vivo study were similar to the in vitro data, demonstrating the highest total-tract aNDF digestibility (70%; NDF analysis conducted with α-amylase and sodium sulfite) for cows fed the corn silage with the lowest ester- and ether-linked pCA content in the NDF fraction. 28780096 12 151 with silage 2449:2454 arg1 content 2500:2506 ether-linked pCA content 2483:2506 ether-linked pCA content 2483:2506 The results from the in vivo study were similar to the in vitro data, demonstrating the highest total-tract aNDF digestibility (70%; NDF analysis conducted with α-amylase and sodium sulfite) for cows fed the corn silage with the lowest ester- and ether-linked pCA content in the NDF fraction. 28780096 8 152 theme pCA 1630:1632 arg1 content 1595:1601 the content 1591:1601 the content of ester- and ether-linked pCA and FA in both NDF and ADF residues 1591:1668 From the in vitro study, the phenolic acid content (total pCA and FA) was highest for corn silages, and overall the content of ester- and ether-linked pCA and FA in both NDF and ADF residues were correlated with NDF digestibility parameters, reflecting the competitive effect of these linkages on digestibility. 28780096 12 153 theme lowest 2465:2470 arg1 ester- 2472:2477 the lowest ester- 2461:2477 the lowest ester- 2461:2477 The results from the in vivo study were similar to the in vitro data, demonstrating the highest total-tract aNDF digestibility (70%; NDF analysis conducted with α-amylase and sodium sulfite) for cows fed the corn silage with the lowest ester- and ether-linked pCA content in the NDF fraction. 28780096 6 154 theme in 1132:1133 arg1 observations 1141:1152 in vitro observations 1132:1152 in vitro observations of ester- and ether-linked pCA and FA and digestibility 1132:1208 To determine whether in vitro observations of ester- and ether-linked pCA and FA and digestibility were similar to in vivo observations, 3 corn silages selected for digestibility were fed to 6 ruminally fistulated cows for 3 wk in 3 iso-NDF diets. 28780096 8 155 from content 1595:1601 arg1 residues 1661:1668 both NDF and ADF residues 1644:1668 residues 1661:1668 From the in vitro study, the phenolic acid content (total pCA and FA) was highest for corn silages, and overall the content of ester- and ether-linked pCA and FA in both NDF and ADF residues were correlated with NDF digestibility parameters, reflecting the competitive effect of these linkages on digestibility. 28780096 5 156 theme digested 942:949 arg1 residues 951:958 Undigested and digested residues 927:958 Undigested and digested residues 927:958 Undigested and digested residues were analyzed for NDF, acid detergent fiber (ADF), ADL, and Klason lignin (KL); ester- and ether-linked pCA and FA were determined in these fractions. 28780096 9 157 theme Klason 1797:1802 arg1 lignin 1804:1809 Klason lignin 1797:1809 Klason lignin 1797:1809 Also, Klason lignin and ADL were negatively correlated with ether-linked ferulic acid on an NDF basis. 28780096 5 158 theme ether-linked 1051:1062 arg1 pCA 1064:1066 ether-linked pCA 1051:1066 ether-linked pCA 1051:1066 Undigested and digested residues were analyzed for NDF, acid detergent fiber (ADF), ADL, and Klason lignin (KL); ester- and ether-linked pCA and FA were determined in these fractions. 26231645 7 0 theme Y 1408:1408 arg1 patterns 1353:1360 different glycosylation and processing patterns 1314:1360 different glycosylation and processing patterns of the vacuolar glycoprotein carboxypeptidase Y 1314:1408 Notably, different glycosylation and processing patterns of the vacuolar glycoprotein carboxypeptidase Y were observed in the WT and Hphac1Δ strains. 26231645 4 1 theme growth 803:808 arg1 conditions 810:819 normal growth conditions 796:819 normal growth conditions 796:819 The H. polymorpha hac1-null (Hphac1Δ) mutant strain grew slowly, even under normal growth conditions, and was less thermotolerant than the wild-type (WT) strain. 26231645 7 2 theme processing 1342:1351 arg1 patterns 1353:1360 different glycosylation and processing patterns 1314:1360 different glycosylation and processing patterns of the vacuolar glycoprotein carboxypeptidase Y 1314:1408 Notably, different glycosylation and processing patterns of the vacuolar glycoprotein carboxypeptidase Y were observed in the WT and Hphac1Δ strains. 26231645 6 3 theme UPR 1161:1163 arg1 those 1254:1258 those 1254:1258 those 1254:1258 Using comparative transcriptome analysis of the WT and Hphac1Δ strains treated with DTT and TM, we identified HpHAC1-dependent core UPR targets, which included genes involved in protein secretion and processing, particularly those required for N-linked protein glycosylation. 26231645 6 3 theme UPR 1161:1163 arg1 targets 1165:1171 HpHAC1-dependent core UPR targets 1139:1171 HpHAC1-dependent core UPR targets 1139:1171 Using comparative transcriptome analysis of the WT and Hphac1Δ strains treated with DTT and TM, we identified HpHAC1-dependent core UPR targets, which included genes involved in protein secretion and processing, particularly those required for N-linked protein glycosylation. 26231645 7 4 theme glycoprotein 1378:1389 arg1 Y 1408:1408 the vacuolar glycoprotein carboxypeptidase Y 1365:1408 the vacuolar glycoprotein carboxypeptidase Y 1365:1408 Notably, different glycosylation and processing patterns of the vacuolar glycoprotein carboxypeptidase Y were observed in the WT and Hphac1Δ strains. 26231645 7 5 theme glycosylation 1324:1336 arg1 patterns 1353:1360 different glycosylation and processing patterns 1314:1360 different glycosylation and processing patterns of the vacuolar glycoprotein carboxypeptidase Y 1314:1408 Notably, different glycosylation and processing patterns of the vacuolar glycoprotein carboxypeptidase Y were observed in the WT and Hphac1Δ strains. 26231645 6 6 theme HpHAC1-dependent 1139:1154 arg1 those 1254:1258 those 1254:1258 those 1254:1258 Using comparative transcriptome analysis of the WT and Hphac1Δ strains treated with DTT and TM, we identified HpHAC1-dependent core UPR targets, which included genes involved in protein secretion and processing, particularly those required for N-linked protein glycosylation. 26231645 6 6 theme HpHAC1-dependent 1139:1154 arg1 targets 1165:1171 HpHAC1-dependent core UPR targets 1139:1171 HpHAC1-dependent core UPR targets 1139:1171 Using comparative transcriptome analysis of the WT and Hphac1Δ strains treated with DTT and TM, we identified HpHAC1-dependent core UPR targets, which included genes involved in protein secretion and processing, particularly those required for N-linked protein glycosylation. 26231645 3 7 with interaction 608:618 arg1 region 645:650 the 5' untranslated region 625:650 the 5' untranslated region 625:650 We found that the HpHAC1 mRNA contains a nonconventional intron of 177 bp whose interaction with the 5' untranslated region is responsible for the translational inhibition of the HpHAC1 mRNA. 26231645 1 8 theme endoplasmic 182:192 arg1 reticulum 194:202 the endoplasmic reticulum 178:202 the endoplasmic reticulum (ER) 178:207 Aggregation of misfolded protein in the endoplasmic reticulum (ER) induces a cellular protective response to ER stress, the unfolded protein response (UPR), which is mediated by a basic leucine zipper (bZIP) transcription factor, Hac1p/Xbp1. 26231645 1 8 theme endoplasmic 182:192 arg1 ER 205:206 ER 205:206 ER 205:206 Aggregation of misfolded protein in the endoplasmic reticulum (ER) induces a cellular protective response to ER stress, the unfolded protein response (UPR), which is mediated by a basic leucine zipper (bZIP) transcription factor, Hac1p/Xbp1. 26231645 9 9 theme HpHac1p 1634:1640 arg1 important 1645:1653 important 1645:1653 important 1645:1653 Collectively, our results suggest that the function of HpHac1p is important not only for UPR induction but also for efficient glycosylation in H. polymorpha. 26231645 9 9 theme HpHac1p 1634:1640 arg1 function 1622:1629 the function 1618:1629 the function of HpHac1p 1618:1640 Collectively, our results suggest that the function of HpHac1p is important not only for UPR induction but also for efficient glycosylation in H. polymorpha. 26231645 6 10 theme comparative 1035:1045 arg1 analysis 1061:1068 comparative transcriptome analysis 1035:1068 comparative transcriptome analysis of the WT and Hphac1Δ strains treated with DTT and TM 1035:1122 Using comparative transcriptome analysis of the WT and Hphac1Δ strains treated with DTT and TM, we identified HpHAC1-dependent core UPR targets, which included genes involved in protein secretion and processing, particularly those required for N-linked protein glycosylation. 26231645 0 11 theme Transcriptomic 117:130 arg1 Analyses 132:139 Functional and Transcriptomic Analyses 102:139 Functional and Transcriptomic Analyses 102:139 Hansenula polymorpha Hac1p Is Critical to Protein N-Glycosylation Activity Modulation, as Revealed by Functional and Transcriptomic Analyses. 26231645 5 12 theme UPR-inducing 966:977 arg1 agents 979:984 the UPR-inducing agents 962:984 the UPR-inducing agents dithiothreitol (DTT) and tunicamycin (TM) 962:1026 The mutant strain was also more sensitive to cell wall-perturbing agents and to the UPR-inducing agents dithiothreitol (DTT) and tunicamycin (TM). 26231645 5 12 theme UPR-inducing 966:977 arg1 tunicamycin 1011:1021 tunicamycin 1011:1021 tunicamycin (TM) 1011:1026 The mutant strain was also more sensitive to cell wall-perturbing agents and to the UPR-inducing agents dithiothreitol (DTT) and tunicamycin (TM). 26231645 5 12 theme UPR-inducing 966:977 arg1 dithiothreitol 986:999 dithiothreitol 986:999 dithiothreitol (DTT) 986:1005 The mutant strain was also more sensitive to cell wall-perturbing agents and to the UPR-inducing agents dithiothreitol (DTT) and tunicamycin (TM). 26231645 2 13 theme yeast 491:495 arg1 HpHAC1 519:524 HpHAC1 519:524 HpHAC1 519:524 In this study, we identified and studied the molecular functions of a HAC1 homolog from the thermotolerant yeast Hansenula polymorpha (HpHAC1). 26231645 2 13 theme yeast 491:495 arg1 polymorpha 507:516 the thermotolerant yeast Hansenula polymorpha 472:516 the thermotolerant yeast Hansenula polymorpha (HpHAC1) 472:525 In this study, we identified and studied the molecular functions of a HAC1 homolog from the thermotolerant yeast Hansenula polymorpha (HpHAC1). 26231645 3 14 theme mRNA 714:717 arg1 inhibition 689:698 the translational inhibition 671:698 the translational inhibition of the HpHAC1 mRNA 671:717 We found that the HpHAC1 mRNA contains a nonconventional intron of 177 bp whose interaction with the 5' untranslated region is responsible for the translational inhibition of the HpHAC1 mRNA. 26231645 4 15 dep wild-type 859:867 arg1 WT 870:871 WT 870:871 WT 870:871 The H. polymorpha hac1-null (Hphac1Δ) mutant strain grew slowly, even under normal growth conditions, and was less thermotolerant than the wild-type (WT) strain. 26231645 1 16 theme transcription 350:362 arg1 Hac1p/Xbp1 372:381 Hac1p/Xbp1 372:381 Hac1p/Xbp1 372:381 Aggregation of misfolded protein in the endoplasmic reticulum (ER) induces a cellular protective response to ER stress, the unfolded protein response (UPR), which is mediated by a basic leucine zipper (bZIP) transcription factor, Hac1p/Xbp1. 26231645 1 16 theme transcription 350:362 arg1 factor 364:369 a basic leucine zipper (bZIP) transcription factor 320:369 a basic leucine zipper (bZIP) transcription factor 320:369 Aggregation of misfolded protein in the endoplasmic reticulum (ER) induces a cellular protective response to ER stress, the unfolded protein response (UPR), which is mediated by a basic leucine zipper (bZIP) transcription factor, Hac1p/Xbp1. 26231645 9 17 theme UPR 1668:1670 arg1 induction 1672:1680 UPR induction 1668:1680 UPR induction 1668:1680 Collectively, our results suggest that the function of HpHac1p is important not only for UPR induction but also for efficient glycosylation in H. polymorpha. 26231645 6 18 theme strains 1092:1098 arg1 analysis 1061:1068 comparative transcriptome analysis 1035:1068 comparative transcriptome analysis of the WT and Hphac1Δ strains treated with DTT and TM 1035:1122 Using comparative transcriptome analysis of the WT and Hphac1Δ strains treated with DTT and TM, we identified HpHAC1-dependent core UPR targets, which included genes involved in protein secretion and processing, particularly those required for N-linked protein glycosylation. 26231645 6 19 theme protein 1282:1288 arg1 glycosylation 1290:1302 N-linked protein glycosylation 1273:1302 N-linked protein glycosylation 1273:1302 Using comparative transcriptome analysis of the WT and Hphac1Δ strains treated with DTT and TM, we identified HpHAC1-dependent core UPR targets, which included genes involved in protein secretion and processing, particularly those required for N-linked protein glycosylation. 26231645 1 20 theme misfolded 157:165 arg1 protein 167:173 misfolded protein 157:173 misfolded protein 157:173 Aggregation of misfolded protein in the endoplasmic reticulum (ER) induces a cellular protective response to ER stress, the unfolded protein response (UPR), which is mediated by a basic leucine zipper (bZIP) transcription factor, Hac1p/Xbp1. 26231645 1 21 theme basic 322:326 arg1 bZIP 344:347 bZIP 344:347 bZIP 344:347 Aggregation of misfolded protein in the endoplasmic reticulum (ER) induces a cellular protective response to ER stress, the unfolded protein response (UPR), which is mediated by a basic leucine zipper (bZIP) transcription factor, Hac1p/Xbp1. 26231645 1 21 theme basic 322:326 arg1 zipper 336:341 basic leucine zipper 322:341 a basic leucine zipper (bZIP) transcription factor 320:369 Aggregation of misfolded protein in the endoplasmic reticulum (ER) induces a cellular protective response to ER stress, the unfolded protein response (UPR), which is mediated by a basic leucine zipper (bZIP) transcription factor, Hac1p/Xbp1. 26231645 7 22 gly glycoprotein 1378:1389 arg1 glycoprotein 1378:1389 the vacuolar glycoprotein carboxypeptidase Y 1365:1408 the vacuolar glycoprotein carboxypeptidase Y 1365:1408 Notably, different glycosylation and processing patterns of the vacuolar glycoprotein carboxypeptidase Y were observed in the WT and Hphac1Δ strains. 26231645 2 23 theme homolog 459:465 arg1 functions 439:447 the molecular functions 425:447 the molecular functions of a HAC1 homolog from the thermotolerant yeast Hansenula polymorpha (HpHAC1) 425:525 In this study, we identified and studied the molecular functions of a HAC1 homolog from the thermotolerant yeast Hansenula polymorpha (HpHAC1). 26231645 0 24 theme Functional 102:111 arg1 Analyses 132:139 Functional and Transcriptomic Analyses 102:139 Functional and Transcriptomic Analyses 102:139 Hansenula polymorpha Hac1p Is Critical to Protein N-Glycosylation Activity Modulation, as Revealed by Functional and Transcriptomic Analyses. 26231645 1 25 theme zipper 336:341 arg1 Hac1p/Xbp1 372:381 Hac1p/Xbp1 372:381 Hac1p/Xbp1 372:381 Aggregation of misfolded protein in the endoplasmic reticulum (ER) induces a cellular protective response to ER stress, the unfolded protein response (UPR), which is mediated by a basic leucine zipper (bZIP) transcription factor, Hac1p/Xbp1. 26231645 1 25 theme zipper 336:341 arg1 factor 364:369 a basic leucine zipper (bZIP) transcription factor 320:369 a basic leucine zipper (bZIP) transcription factor 320:369 Aggregation of misfolded protein in the endoplasmic reticulum (ER) induces a cellular protective response to ER stress, the unfolded protein response (UPR), which is mediated by a basic leucine zipper (bZIP) transcription factor, Hac1p/Xbp1. 26231645 5 26 theme mutant 886:891 arg1 strain 893:898 The mutant strain 882:898 The mutant strain 882:898 The mutant strain was also more sensitive to cell wall-perturbing agents and to the UPR-inducing agents dithiothreitol (DTT) and tunicamycin (TM). 26231645 5 26 theme mutant 886:891 arg1 sensitive 914:922 sensitive 914:922 sensitive 914:922 The mutant strain was also more sensitive to cell wall-perturbing agents and to the UPR-inducing agents dithiothreitol (DTT) and tunicamycin (TM). 26231645 0 27 theme Hansenula 0:8 arg1 polymorpha 10:19 Hansenula polymorpha 0:19 Hansenula polymorpha Hac1p 0:25 Hansenula polymorpha Hac1p Is Critical to Protein N-Glycosylation Activity Modulation, as Revealed by Functional and Transcriptomic Analyses. 26231645 1 28 theme unfolded 266:273 arg1 response 283:290 the unfolded protein response 262:290 the unfolded protein response (UPR) 262:296 Aggregation of misfolded protein in the endoplasmic reticulum (ER) induces a cellular protective response to ER stress, the unfolded protein response (UPR), which is mediated by a basic leucine zipper (bZIP) transcription factor, Hac1p/Xbp1. 26231645 1 28 theme unfolded 266:273 arg1 response 239:246 a cellular protective response 217:246 a cellular protective response to ER stress 217:259 Aggregation of misfolded protein in the endoplasmic reticulum (ER) induces a cellular protective response to ER stress, the unfolded protein response (UPR), which is mediated by a basic leucine zipper (bZIP) transcription factor, Hac1p/Xbp1. 26231645 1 28 theme unfolded 266:273 arg1 UPR 293:295 UPR 293:295 UPR 293:295 Aggregation of misfolded protein in the endoplasmic reticulum (ER) induces a cellular protective response to ER stress, the unfolded protein response (UPR), which is mediated by a basic leucine zipper (bZIP) transcription factor, Hac1p/Xbp1. 26231645 4 29 theme Hphac1Δ 749:755 arg1 thermotolerant 835:848 thermotolerant 835:848 thermotolerant 835:848 The H. polymorpha hac1-null (Hphac1Δ) mutant strain grew slowly, even under normal growth conditions, and was less thermotolerant than the wild-type (WT) strain. 26231645 4 29 theme Hphac1Δ 749:755 arg1 strain 765:770 The H. polymorpha hac1-null (Hphac1Δ) mutant strain 720:770 The H. polymorpha hac1-null (Hphac1Δ) mutant strain 720:770 The H. polymorpha hac1-null (Hphac1Δ) mutant strain grew slowly, even under normal growth conditions, and was less thermotolerant than the wild-type (WT) strain. 26231645 9 30 from glycosylation 1705:1717 arg1 H. 1722:1723 H. 1722:1723 H. 1722:1723 Collectively, our results suggest that the function of HpHac1p is important not only for UPR induction but also for efficient glycosylation in H. polymorpha. 26231645 8 31 theme HpHac1p 1490:1496 arg1 overexpression 1465:1478 overexpression 1465:1478 overexpression of active HpHac1p 1465:1496 Moreover, overexpression of active HpHac1p significantly increased the N-linked glycosylation efficiency and TM resistance. 26231645 0 32 theme Activity 66:73 arg1 Modulation 75:84 Protein N-Glycosylation Activity Modulation 42:84 Protein N-Glycosylation Activity Modulation 42:84 Hansenula polymorpha Hac1p Is Critical to Protein N-Glycosylation Activity Modulation, as Revealed by Functional and Transcriptomic Analyses. 26231645 4 33 theme mutant 758:763 arg1 thermotolerant 835:848 thermotolerant 835:848 thermotolerant 835:848 The H. polymorpha hac1-null (Hphac1Δ) mutant strain grew slowly, even under normal growth conditions, and was less thermotolerant than the wild-type (WT) strain. 26231645 4 33 theme mutant 758:763 arg1 strain 765:770 The H. polymorpha hac1-null (Hphac1Δ) mutant strain 720:770 The H. polymorpha hac1-null (Hphac1Δ) mutant strain 720:770 The H. polymorpha hac1-null (Hphac1Δ) mutant strain grew slowly, even under normal growth conditions, and was less thermotolerant than the wild-type (WT) strain. 26231645 0 34 theme Protein 42:48 arg1 Modulation 75:84 Protein N-Glycosylation Activity Modulation 42:84 Protein N-Glycosylation Activity Modulation 42:84 Hansenula polymorpha Hac1p Is Critical to Protein N-Glycosylation Activity Modulation, as Revealed by Functional and Transcriptomic Analyses. 26231645 7 35 theme WT 1431:1432 arg1 strains 1446:1452 the WT and Hphac1Δ strains 1427:1452 the WT and Hphac1Δ strains 1427:1452 Notably, different glycosylation and processing patterns of the vacuolar glycoprotein carboxypeptidase Y were observed in the WT and Hphac1Δ strains. 26231645 5 36 theme wall-perturbing 932:946 arg1 agents 948:953 cell wall-perturbing agents 927:953 cell wall-perturbing agents 927:953 The mutant strain was also more sensitive to cell wall-perturbing agents and to the UPR-inducing agents dithiothreitol (DTT) and tunicamycin (TM). 26231645 7 37 theme Hphac1Δ 1438:1444 arg1 strains 1446:1452 the WT and Hphac1Δ strains 1427:1452 the WT and Hphac1Δ strains 1427:1452 Notably, different glycosylation and processing patterns of the vacuolar glycoprotein carboxypeptidase Y were observed in the WT and Hphac1Δ strains. 26231645 4 38 theme H. 724:725 arg1 thermotolerant 835:848 thermotolerant 835:848 thermotolerant 835:848 The H. polymorpha hac1-null (Hphac1Δ) mutant strain grew slowly, even under normal growth conditions, and was less thermotolerant than the wild-type (WT) strain. 26231645 4 38 theme H. 724:725 arg1 strain 765:770 The H. polymorpha hac1-null (Hphac1Δ) mutant strain 720:770 The H. polymorpha hac1-null (Hphac1Δ) mutant strain 720:770 The H. polymorpha hac1-null (Hphac1Δ) mutant strain grew slowly, even under normal growth conditions, and was less thermotolerant than the wild-type (WT) strain. 26231645 1 39 theme cellular 219:226 arg1 response 239:246 a cellular protective response 217:246 a cellular protective response to ER stress 217:259 Aggregation of misfolded protein in the endoplasmic reticulum (ER) induces a cellular protective response to ER stress, the unfolded protein response (UPR), which is mediated by a basic leucine zipper (bZIP) transcription factor, Hac1p/Xbp1. 26231645 1 39 theme cellular 219:226 arg1 response 283:290 the unfolded protein response 262:290 the unfolded protein response (UPR) 262:296 Aggregation of misfolded protein in the endoplasmic reticulum (ER) induces a cellular protective response to ER stress, the unfolded protein response (UPR), which is mediated by a basic leucine zipper (bZIP) transcription factor, Hac1p/Xbp1. 26231645 8 40 theme N-linked 1526:1533 arg1 efficiency 1549:1558 the N-linked glycosylation efficiency 1522:1558 the N-linked glycosylation efficiency 1522:1558 Moreover, overexpression of active HpHac1p significantly increased the N-linked glycosylation efficiency and TM resistance. 26231645 4 41 theme hac1-null 738:746 arg1 thermotolerant 835:848 thermotolerant 835:848 thermotolerant 835:848 The H. polymorpha hac1-null (Hphac1Δ) mutant strain grew slowly, even under normal growth conditions, and was less thermotolerant than the wild-type (WT) strain. 26231645 4 41 theme hac1-null 738:746 arg1 strain 765:770 The H. polymorpha hac1-null (Hphac1Δ) mutant strain 720:770 The H. polymorpha hac1-null (Hphac1Δ) mutant strain 720:770 The H. polymorpha hac1-null (Hphac1Δ) mutant strain grew slowly, even under normal growth conditions, and was less thermotolerant than the wild-type (WT) strain. 26231645 5 42 dep agents 979:984 arg1 TM 1024:1025 TM 1024:1025 TM 1024:1025 The mutant strain was also more sensitive to cell wall-perturbing agents and to the UPR-inducing agents dithiothreitol (DTT) and tunicamycin (TM). 26231645 5 42 dep agents 979:984 arg1 DTT 1002:1004 DTT 1002:1004 DTT 1002:1004 The mutant strain was also more sensitive to cell wall-perturbing agents and to the UPR-inducing agents dithiothreitol (DTT) and tunicamycin (TM). 26231645 5 42 dep agents 979:984 arg1 tunicamycin 1011:1021 tunicamycin 1011:1021 tunicamycin (TM) 1011:1026 The mutant strain was also more sensitive to cell wall-perturbing agents and to the UPR-inducing agents dithiothreitol (DTT) and tunicamycin (TM). 26231645 5 42 dep agents 979:984 arg1 dithiothreitol 986:999 dithiothreitol 986:999 dithiothreitol (DTT) 986:1005 The mutant strain was also more sensitive to cell wall-perturbing agents and to the UPR-inducing agents dithiothreitol (DTT) and tunicamycin (TM). 26231645 5 42 dep agents 979:984 arg1 agents 979:984 the UPR-inducing agents 962:984 the UPR-inducing agents dithiothreitol (DTT) and tunicamycin (TM) 962:1026 The mutant strain was also more sensitive to cell wall-perturbing agents and to the UPR-inducing agents dithiothreitol (DTT) and tunicamycin (TM). 26231645 3 43 theme untranslated 632:643 arg1 region 645:650 the 5' untranslated region 625:650 the 5' untranslated region 625:650 We found that the HpHAC1 mRNA contains a nonconventional intron of 177 bp whose interaction with the 5' untranslated region is responsible for the translational inhibition of the HpHAC1 mRNA. 26231645 1 44 theme ER 251:252 arg1 stress 254:259 ER stress 251:259 ER stress 251:259 Aggregation of misfolded protein in the endoplasmic reticulum (ER) induces a cellular protective response to ER stress, the unfolded protein response (UPR), which is mediated by a basic leucine zipper (bZIP) transcription factor, Hac1p/Xbp1. 26231645 7 45 theme carboxypeptidase 1391:1406 arg1 Y 1408:1408 the vacuolar glycoprotein carboxypeptidase Y 1365:1408 the vacuolar glycoprotein carboxypeptidase Y 1365:1408 Notably, different glycosylation and processing patterns of the vacuolar glycoprotein carboxypeptidase Y were observed in the WT and Hphac1Δ strains. 26231645 8 46 theme TM 1564:1565 arg1 resistance 1567:1576 TM resistance 1564:1576 TM resistance 1564:1576 Moreover, overexpression of active HpHac1p significantly increased the N-linked glycosylation efficiency and TM resistance. 26231645 7 47 theme vacuolar 1369:1376 arg1 Y 1408:1408 the vacuolar glycoprotein carboxypeptidase Y 1365:1408 the vacuolar glycoprotein carboxypeptidase Y 1365:1408 Notably, different glycosylation and processing patterns of the vacuolar glycoprotein carboxypeptidase Y were observed in the WT and Hphac1Δ strains. 26231645 4 48 theme normal 796:801 arg1 conditions 810:819 normal growth conditions 796:819 normal growth conditions 796:819 The H. polymorpha hac1-null (Hphac1Δ) mutant strain grew slowly, even under normal growth conditions, and was less thermotolerant than the wild-type (WT) strain. 26231645 6 49 theme WT 1077:1078 arg1 strains 1092:1098 the WT and Hphac1Δ strains 1073:1098 the WT and Hphac1Δ strains treated with DTT and TM 1073:1122 Using comparative transcriptome analysis of the WT and Hphac1Δ strains treated with DTT and TM, we identified HpHAC1-dependent core UPR targets, which included genes involved in protein secretion and processing, particularly those required for N-linked protein glycosylation. 26231645 6 50 theme core 1156:1159 arg1 those 1254:1258 those 1254:1258 those 1254:1258 Using comparative transcriptome analysis of the WT and Hphac1Δ strains treated with DTT and TM, we identified HpHAC1-dependent core UPR targets, which included genes involved in protein secretion and processing, particularly those required for N-linked protein glycosylation. 26231645 6 50 theme core 1156:1159 arg1 targets 1165:1171 HpHAC1-dependent core UPR targets 1139:1171 HpHAC1-dependent core UPR targets 1139:1171 Using comparative transcriptome analysis of the WT and Hphac1Δ strains treated with DTT and TM, we identified HpHAC1-dependent core UPR targets, which included genes involved in protein secretion and processing, particularly those required for N-linked protein glycosylation. 26231645 7 51 gly glycosylation 1324:1336 arg1 Y 1408:1408 the vacuolar glycoprotein carboxypeptidase Y 1365:1408 the vacuolar glycoprotein carboxypeptidase Y 1365:1408 Notably, different glycosylation and processing patterns of the vacuolar glycoprotein carboxypeptidase Y were observed in the WT and Hphac1Δ strains. 26231645 9 52 theme efficient 1695:1703 arg1 glycosylation 1705:1717 efficient glycosylation 1695:1717 efficient glycosylation in H. polymorpha 1695:1734 Collectively, our results suggest that the function of HpHac1p is important not only for UPR induction but also for efficient glycosylation in H. polymorpha. 26231645 4 53 dep H. 724:725 arg1 polymorpha 727:736 H. polymorpha 724:736 The H. polymorpha hac1-null (Hphac1Δ) mutant strain 720:770 The H. polymorpha hac1-null (Hphac1Δ) mutant strain grew slowly, even under normal growth conditions, and was less thermotolerant than the wild-type (WT) strain. 26231645 6 54 theme transcriptome 1047:1059 arg1 analysis 1061:1068 comparative transcriptome analysis 1035:1068 comparative transcriptome analysis of the WT and Hphac1Δ strains treated with DTT and TM 1035:1122 Using comparative transcriptome analysis of the WT and Hphac1Δ strains treated with DTT and TM, we identified HpHAC1-dependent core UPR targets, which included genes involved in protein secretion and processing, particularly those required for N-linked protein glycosylation. 26231645 7 55 theme different 1314:1322 arg1 patterns 1353:1360 different glycosylation and processing patterns 1314:1360 different glycosylation and processing patterns of the vacuolar glycoprotein carboxypeptidase Y 1314:1408 Notably, different glycosylation and processing patterns of the vacuolar glycoprotein carboxypeptidase Y were observed in the WT and Hphac1Δ strains. 26231645 2 56 theme Hansenula 497:505 arg1 HpHAC1 519:524 HpHAC1 519:524 HpHAC1 519:524 In this study, we identified and studied the molecular functions of a HAC1 homolog from the thermotolerant yeast Hansenula polymorpha (HpHAC1). 26231645 2 56 theme Hansenula 497:505 arg1 polymorpha 507:516 the thermotolerant yeast Hansenula polymorpha 472:516 the thermotolerant yeast Hansenula polymorpha (HpHAC1) 472:525 In this study, we identified and studied the molecular functions of a HAC1 homolog from the thermotolerant yeast Hansenula polymorpha (HpHAC1). 26231645 2 57 from functions 439:447 arg1 HpHAC1 519:524 HpHAC1 519:524 HpHAC1 519:524 In this study, we identified and studied the molecular functions of a HAC1 homolog from the thermotolerant yeast Hansenula polymorpha (HpHAC1). 26231645 2 57 from functions 439:447 arg1 polymorpha 507:516 the thermotolerant yeast Hansenula polymorpha 472:516 the thermotolerant yeast Hansenula polymorpha (HpHAC1) 472:525 In this study, we identified and studied the molecular functions of a HAC1 homolog from the thermotolerant yeast Hansenula polymorpha (HpHAC1). 26231645 3 58 theme translational 675:687 arg1 inhibition 689:698 the translational inhibition 671:698 the translational inhibition of the HpHAC1 mRNA 671:717 We found that the HpHAC1 mRNA contains a nonconventional intron of 177 bp whose interaction with the 5' untranslated region is responsible for the translational inhibition of the HpHAC1 mRNA. 26231645 2 59 theme thermotolerant 476:489 arg1 HpHAC1 519:524 HpHAC1 519:524 HpHAC1 519:524 In this study, we identified and studied the molecular functions of a HAC1 homolog from the thermotolerant yeast Hansenula polymorpha (HpHAC1). 26231645 2 59 theme thermotolerant 476:489 arg1 polymorpha 507:516 the thermotolerant yeast Hansenula polymorpha 472:516 the thermotolerant yeast Hansenula polymorpha (HpHAC1) 472:525 In this study, we identified and studied the molecular functions of a HAC1 homolog from the thermotolerant yeast Hansenula polymorpha (HpHAC1). 26231645 8 60 link N-linked 1526:1533 arg1 efficiency 1549:1558 the N-linked glycosylation efficiency 1522:1558 the N-linked glycosylation efficiency 1522:1558 Moreover, overexpression of active HpHac1p significantly increased the N-linked glycosylation efficiency and TM resistance. 26231645 3 61 theme HpHAC1 707:712 arg1 mRNA 714:717 the HpHAC1 mRNA 703:717 the HpHAC1 mRNA 703:717 We found that the HpHAC1 mRNA contains a nonconventional intron of 177 bp whose interaction with the 5' untranslated region is responsible for the translational inhibition of the HpHAC1 mRNA. 26231645 3 62 theme HpHAC1 546:551 arg1 mRNA 553:556 the HpHAC1 mRNA 542:556 the HpHAC1 mRNA 542:556 We found that the HpHAC1 mRNA contains a nonconventional intron of 177 bp whose interaction with the 5' untranslated region is responsible for the translational inhibition of the HpHAC1 mRNA. 26231645 9 63 gly glycosylation 1705:1717 arg1 H. 1722:1723 H. 1722:1723 H. 1722:1723 Collectively, our results suggest that the function of HpHac1p is important not only for UPR induction but also for efficient glycosylation in H. polymorpha. 26231645 7 64 located observed 1415:1422 arg2 patterns 1353:1360 different glycosylation and processing patterns 1314:1360 different glycosylation and processing patterns of the vacuolar glycoprotein carboxypeptidase Y 1314:1408 Notably, different glycosylation and processing patterns of the vacuolar glycoprotein carboxypeptidase Y were observed in the WT and Hphac1Δ strains. 26231645 7 64 located observed 1415:1422 arg1 strains 1446:1452 the WT and Hphac1Δ strains 1427:1452 the WT and Hphac1Δ strains 1427:1452 Notably, different glycosylation and processing patterns of the vacuolar glycoprotein carboxypeptidase Y were observed in the WT and Hphac1Δ strains. 26231645 6 65 theme Hphac1Δ 1084:1090 arg1 strains 1092:1098 the WT and Hphac1Δ strains 1073:1098 the WT and Hphac1Δ strains treated with DTT and TM 1073:1122 Using comparative transcriptome analysis of the WT and Hphac1Δ strains treated with DTT and TM, we identified HpHAC1-dependent core UPR targets, which included genes involved in protein secretion and processing, particularly those required for N-linked protein glycosylation. 26231645 6 66 theme N-linked 1273:1280 arg1 glycosylation 1290:1302 N-linked protein glycosylation 1273:1302 N-linked protein glycosylation 1273:1302 Using comparative transcriptome analysis of the WT and Hphac1Δ strains treated with DTT and TM, we identified HpHAC1-dependent core UPR targets, which included genes involved in protein secretion and processing, particularly those required for N-linked protein glycosylation. 26231645 1 67 theme protein 167:173 arg1 Aggregation 142:152 Aggregation 142:152 Aggregation of misfolded protein in the endoplasmic reticulum (ER) 142:207 Aggregation of misfolded protein in the endoplasmic reticulum (ER) induces a cellular protective response to ER stress, the unfolded protein response (UPR), which is mediated by a basic leucine zipper (bZIP) transcription factor, Hac1p/Xbp1. 26231645 2 68 theme molecular 429:437 arg1 functions 439:447 the molecular functions 425:447 the molecular functions of a HAC1 homolog from the thermotolerant yeast Hansenula polymorpha (HpHAC1) 425:525 In this study, we identified and studied the molecular functions of a HAC1 homolog from the thermotolerant yeast Hansenula polymorpha (HpHAC1). 26231645 6 69 link N-linked 1273:1280 arg1 glycosylation 1290:1302 N-linked protein glycosylation 1273:1302 N-linked protein glycosylation 1273:1302 Using comparative transcriptome analysis of the WT and Hphac1Δ strains treated with DTT and TM, we identified HpHAC1-dependent core UPR targets, which included genes involved in protein secretion and processing, particularly those required for N-linked protein glycosylation. 26231645 4 70 theme wild-type 859:867 arg1 strain 874:879 the wild-type (WT) strain 855:879 the wild-type (WT) strain 855:879 The H. polymorpha hac1-null (Hphac1Δ) mutant strain grew slowly, even under normal growth conditions, and was less thermotolerant than the wild-type (WT) strain. 26231645 1 71 theme leucine 328:334 arg1 bZIP 344:347 bZIP 344:347 bZIP 344:347 Aggregation of misfolded protein in the endoplasmic reticulum (ER) induces a cellular protective response to ER stress, the unfolded protein response (UPR), which is mediated by a basic leucine zipper (bZIP) transcription factor, Hac1p/Xbp1. 26231645 1 71 theme leucine 328:334 arg1 zipper 336:341 basic leucine zipper 322:341 a basic leucine zipper (bZIP) transcription factor 320:369 Aggregation of misfolded protein in the endoplasmic reticulum (ER) induces a cellular protective response to ER stress, the unfolded protein response (UPR), which is mediated by a basic leucine zipper (bZIP) transcription factor, Hac1p/Xbp1. 26231645 2 72 theme HAC1 454:457 arg1 homolog 459:465 a HAC1 homolog 452:465 a HAC1 homolog from the thermotolerant yeast Hansenula polymorpha (HpHAC1) 452:525 In this study, we identified and studied the molecular functions of a HAC1 homolog from the thermotolerant yeast Hansenula polymorpha (HpHAC1). 26231645 0 73 theme polymorpha 10:19 arg1 Hac1p 21:25 Hansenula polymorpha Hac1p 0:25 Hansenula polymorpha Hac1p 0:25 Hansenula polymorpha Hac1p Is Critical to Protein N-Glycosylation Activity Modulation, as Revealed by Functional and Transcriptomic Analyses. 26231645 1 74 from Aggregation 142:152 arg1 reticulum 194:202 the endoplasmic reticulum 178:202 the endoplasmic reticulum (ER) 178:207 Aggregation of misfolded protein in the endoplasmic reticulum (ER) induces a cellular protective response to ER stress, the unfolded protein response (UPR), which is mediated by a basic leucine zipper (bZIP) transcription factor, Hac1p/Xbp1. 26231645 1 74 from Aggregation 142:152 arg1 ER 205:206 ER 205:206 ER 205:206 Aggregation of misfolded protein in the endoplasmic reticulum (ER) induces a cellular protective response to ER stress, the unfolded protein response (UPR), which is mediated by a basic leucine zipper (bZIP) transcription factor, Hac1p/Xbp1. 26231645 1 75 theme protein 275:281 arg1 response 283:290 the unfolded protein response 262:290 the unfolded protein response (UPR) 262:296 Aggregation of misfolded protein in the endoplasmic reticulum (ER) induces a cellular protective response to ER stress, the unfolded protein response (UPR), which is mediated by a basic leucine zipper (bZIP) transcription factor, Hac1p/Xbp1. 26231645 1 75 theme protein 275:281 arg1 response 239:246 a cellular protective response 217:246 a cellular protective response to ER stress 217:259 Aggregation of misfolded protein in the endoplasmic reticulum (ER) induces a cellular protective response to ER stress, the unfolded protein response (UPR), which is mediated by a basic leucine zipper (bZIP) transcription factor, Hac1p/Xbp1. 26231645 1 75 theme protein 275:281 arg1 UPR 293:295 UPR 293:295 UPR 293:295 Aggregation of misfolded protein in the endoplasmic reticulum (ER) induces a cellular protective response to ER stress, the unfolded protein response (UPR), which is mediated by a basic leucine zipper (bZIP) transcription factor, Hac1p/Xbp1. 26231645 8 76 theme active 1483:1488 arg1 HpHac1p 1490:1496 active HpHac1p 1483:1496 active HpHac1p 1483:1496 Moreover, overexpression of active HpHac1p significantly increased the N-linked glycosylation efficiency and TM resistance. 26231645 3 77 theme nonconventional 569:583 arg1 intron 585:590 a nonconventional intron 567:590 a nonconventional intron of 177 bp whose interaction with the 5' untranslated region is responsible for the translational inhibition of the HpHAC1 mRNA 567:717 We found that the HpHAC1 mRNA contains a nonconventional intron of 177 bp whose interaction with the 5' untranslated region is responsible for the translational inhibition of the HpHAC1 mRNA. 26231645 0 78 theme N-Glycosylation 50:64 arg1 Modulation 75:84 Protein N-Glycosylation Activity Modulation 42:84 Protein N-Glycosylation Activity Modulation 42:84 Hansenula polymorpha Hac1p Is Critical to Protein N-Glycosylation Activity Modulation, as Revealed by Functional and Transcriptomic Analyses. 26231645 5 79 theme cell 927:930 arg1 agents 948:953 cell wall-perturbing agents 927:953 cell wall-perturbing agents 927:953 The mutant strain was also more sensitive to cell wall-perturbing agents and to the UPR-inducing agents dithiothreitol (DTT) and tunicamycin (TM). 26231645 6 80 theme protein 1207:1213 arg1 secretion 1215:1223 protein secretion 1207:1223 protein secretion 1207:1223 Using comparative transcriptome analysis of the WT and Hphac1Δ strains treated with DTT and TM, we identified HpHAC1-dependent core UPR targets, which included genes involved in protein secretion and processing, particularly those required for N-linked protein glycosylation. 26231645 8 81 theme glycosylation 1535:1547 arg1 efficiency 1549:1558 the N-linked glycosylation efficiency 1522:1558 the N-linked glycosylation efficiency 1522:1558 Moreover, overexpression of active HpHac1p significantly increased the N-linked glycosylation efficiency and TM resistance. 26231645 3 82 theme bp 599:600 arg1 intron 585:590 a nonconventional intron 567:590 a nonconventional intron of 177 bp whose interaction with the 5' untranslated region is responsible for the translational inhibition of the HpHAC1 mRNA 567:717 We found that the HpHAC1 mRNA contains a nonconventional intron of 177 bp whose interaction with the 5' untranslated region is responsible for the translational inhibition of the HpHAC1 mRNA. 26231645 1 83 theme protective 228:237 arg1 response 239:246 a cellular protective response 217:246 a cellular protective response to ER stress 217:259 Aggregation of misfolded protein in the endoplasmic reticulum (ER) induces a cellular protective response to ER stress, the unfolded protein response (UPR), which is mediated by a basic leucine zipper (bZIP) transcription factor, Hac1p/Xbp1. 26231645 1 83 theme protective 228:237 arg1 response 283:290 the unfolded protein response 262:290 the unfolded protein response (UPR) 262:296 Aggregation of misfolded protein in the endoplasmic reticulum (ER) induces a cellular protective response to ER stress, the unfolded protein response (UPR), which is mediated by a basic leucine zipper (bZIP) transcription factor, Hac1p/Xbp1. 26231645 2 84 from polymorpha 507:516 arg1 homolog 459:465 a HAC1 homolog 452:465 a HAC1 homolog from the thermotolerant yeast Hansenula polymorpha (HpHAC1) 452:525 In this study, we identified and studied the molecular functions of a HAC1 homolog from the thermotolerant yeast Hansenula polymorpha (HpHAC1). 26231645 2 84 from polymorpha 507:516 arg1 functions 439:447 the molecular functions 425:447 the molecular functions of a HAC1 homolog from the thermotolerant yeast Hansenula polymorpha (HpHAC1) 425:525 In this study, we identified and studied the molecular functions of a HAC1 homolog from the thermotolerant yeast Hansenula polymorpha (HpHAC1). 26231645 3 85 contain contains 558:565 arg1 mRNA 553:556 the HpHAC1 mRNA 542:556 the HpHAC1 mRNA 542:556 We found that the HpHAC1 mRNA contains a nonconventional intron of 177 bp whose interaction with the 5' untranslated region is responsible for the translational inhibition of the HpHAC1 mRNA. 26231645 3 85 contain contains 558:565 arg2 intron 585:590 a nonconventional intron 567:590 a nonconventional intron of 177 bp whose interaction with the 5' untranslated region is responsible for the translational inhibition of the HpHAC1 mRNA 567:717 We found that the HpHAC1 mRNA contains a nonconventional intron of 177 bp whose interaction with the 5' untranslated region is responsible for the translational inhibition of the HpHAC1 mRNA. 27801529 1 0 theme reference 592:600 arg1 data 602:605 reference data 592:605 reference data 592:605 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 1 1 theme mucin 245:249 arg1 detection 227:235 immunohistochemical detection 207:235 immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal 207:627 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 2 2 theme cells 695:699 arg1 layer 720:724 the underlying layer 705:724 the underlying layer of intermediate cells 705:746 Muc1 mucin was detected in the secreting granules of superficial cells and the underlying layer of intermediate cells. 27801529 2 2 theme cells 695:699 arg1 granules 671:678 the secreting granules 657:678 the secreting granules of superficial cells 657:699 Muc1 mucin was detected in the secreting granules of superficial cells and the underlying layer of intermediate cells. 27801529 8 3 attach linked 1683:1688 arg1 glycoprotein 1697:1708 the glycoprotein 1693:1708 the glycoprotein 1693:1708 The co-distribution of Muc1 and saccharidic residues suggests that many of them are linked to the glycoprotein. 27801529 8 3 attach linked 1683:1688 arg2 them 1674:1677 them 1674:1677 them 1674:1677 The co-distribution of Muc1 and saccharidic residues suggests that many of them are linked to the glycoprotein. 27801529 8 3 attach linked 1683:1688 arg2 many 1666:1669 many 1666:1669 many 1666:1669 The co-distribution of Muc1 and saccharidic residues suggests that many of them are linked to the glycoprotein. 27801529 5 4 from present 1056:1062 arg1 cells 1010:1014 both superficial and intermediate cells 976:1014 both superficial and intermediate cells 976:1014 In both superficial and intermediate cells sulfated and/or sialylated glycans were present, sulfation decreasing in the deeper layers. 27801529 1 5 theme PNA 407:409 arg1 SNA 478:480 PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA 407:480 SNA 478:480 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 1 5 theme PNA 407:409 arg1 lectins 398:404 13 lectins 395:404 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal 395:627 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 1 6 theme anti 254:257 arg1 MUC1 259:262 anti MUC1 254:262 anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal 254:627 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 3 7 theme O-linked 889:896 arg1 chains 875:880 the oligosaccharidic chains 854:880 the oligosaccharidic chains mostly O-linked to proteins 854:908 The secreting granules in both intermediate cells and superficial cells were rich in carbohydrates, with the oligosaccharidic chains mostly O-linked to proteins. 27801529 2 8 theme Muc1 630:633 arg1 mucin 635:639 Muc1 mucin 630:639 Muc1 mucin 630:639 Muc1 mucin was detected in the secreting granules of superficial cells and the underlying layer of intermediate cells. 27801529 1 9 theme model 616:620 arg1 animal 622:627 this model animal 611:627 this model animal 611:627 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 3 10 with rich 826:829 arg1 chains 875:880 the oligosaccharidic chains 854:880 the oligosaccharidic chains mostly O-linked to proteins 854:908 The secreting granules in both intermediate cells and superficial cells were rich in carbohydrates, with the oligosaccharidic chains mostly O-linked to proteins. 27801529 6 11 theme α1,2 1301:1304 arg1 GlcNAc 1309:1314 α1,2 to GlcNAc 1301:1314 α1,2 to GlcNAc 1301:1314 Lectin-binding detected presence of terminal sialic acid linked mostly in α2,6 to GalNAc, Gal terminal or subterminal to sulfates, GalNAc, GlcNAc, and Fuc, mostly linked in α1,6, α1,3 α1,4 and α1,2 to GlcNAc or Gal, but not to lactosamine chains. 27801529 1 12 theme male 158:161 arg1 pigs 172:175 10 adult male Landrace pigs 149:175 10 adult male Landrace pigs 149:175 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 5 13 attach present 1056:1062 arg2 glycans 1043:1049 sulfated and/or sialylated glycans 1016:1049 sulfated and/or sialylated glycans 1016:1049 In both superficial and intermediate cells sulfated and/or sialylated glycans were present, sulfation decreasing in the deeper layers. 27801529 5 13 attach present 1056:1062 arg1 cells 1010:1014 both superficial and intermediate cells 976:1014 both superficial and intermediate cells 976:1014 In both superficial and intermediate cells sulfated and/or sialylated glycans were present, sulfation decreasing in the deeper layers. 27801529 6 14 attach linked 1165:1170 arg2 acid 1160:1163 terminal sialic acid 1144:1163 terminal sialic acid linked mostly in α2,6 to GalNAc, Gal terminal or subterminal to sulfates, GalNAc, GlcNAc, and Fuc, mostly linked in α1,6, α1,3 α1,4 and α1,2 to GlcNAc or Gal, but not to lactosamine chains 1144:1352 Lectin-binding detected presence of terminal sialic acid linked mostly in α2,6 to GalNAc, Gal terminal or subterminal to sulfates, GalNAc, GlcNAc, and Fuc, mostly linked in α1,6, α1,3 α1,4 and α1,2 to GlcNAc or Gal, but not to lactosamine chains. 27801529 6 14 attach linked 1165:1170 arg1 GalNAc 1190:1195 GalNAc 1190:1195 GalNAc 1190:1195 Lectin-binding detected presence of terminal sialic acid linked mostly in α2,6 to GalNAc, Gal terminal or subterminal to sulfates, GalNAc, GlcNAc, and Fuc, mostly linked in α1,6, α1,3 α1,4 and α1,2 to GlcNAc or Gal, but not to lactosamine chains. 27801529 6 14 attach linked 1165:1170 arg3 α2,6 1182:1185 α2,6 1182:1185 α2,6 1182:1185 Lectin-binding detected presence of terminal sialic acid linked mostly in α2,6 to GalNAc, Gal terminal or subterminal to sulfates, GalNAc, GlcNAc, and Fuc, mostly linked in α1,6, α1,3 α1,4 and α1,2 to GlcNAc or Gal, but not to lactosamine chains. 27801529 6 14 attach linked 1165:1170 arg1 chains 1347:1352 lactosamine chains 1335:1352 lactosamine chains 1335:1352 Lectin-binding detected presence of terminal sialic acid linked mostly in α2,6 to GalNAc, Gal terminal or subterminal to sulfates, GalNAc, GlcNAc, and Fuc, mostly linked in α1,6, α1,3 α1,4 and α1,2 to GlcNAc or Gal, but not to lactosamine chains. 27801529 6 15 theme acid 1160:1163 arg1 presence 1132:1139 presence 1132:1139 presence of terminal sialic acid linked mostly in α2,6 to GalNAc, Gal terminal or subterminal to sulfates, GalNAc, GlcNAc, and Fuc, mostly linked in α1,6, α1,3 α1,4 and α1,2 to GlcNAc or Gal, but not to lactosamine chains 1132:1352 Lectin-binding detected presence of terminal sialic acid linked mostly in α2,6 to GalNAc, Gal terminal or subterminal to sulfates, GalNAc, GlcNAc, and Fuc, mostly linked in α1,6, α1,3 α1,4 and α1,2 to GlcNAc or Gal, but not to lactosamine chains. 27801529 1 16 theme pigs 172:175 arg1 bladder 138:144 urinary bladder 130:144 urinary bladder of 10 adult male Landrace pigs 130:175 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 7 17 gly glycoproteins 1415:1427 arg1 glycoproteins 1415:1427 the glycoproteins 1411:1427 the glycoproteins of the urothelium of pig urinary bladder 1411:1468 Except for fucosylation, the oligosaccharidic chains in the glycoproteins of the urothelium of pig urinary bladder were similar to those linked to human MUC1, which is fundamental in cell adhesion and immunological processes in the urothelium. 27801529 1 18 theme High-Iron 358:366 arg1 Diamine 368:374 High-Iron Diamine 358:374 High-Iron Diamine 358:374 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 1 18 theme High-Iron 358:366 arg1 Schiff 330:335 Periodic-Acid Schiff 316:335 Periodic-Acid Schiff 316:335 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 6 19 theme sialic 1153:1158 arg1 acid 1160:1163 terminal sialic acid 1144:1163 terminal sialic acid linked mostly in α2,6 to GalNAc, Gal terminal or subterminal to sulfates, GalNAc, GlcNAc, and Fuc, mostly linked in α1,6, α1,3 α1,4 and α1,2 to GlcNAc or Gal, but not to lactosamine chains 1144:1352 Lectin-binding detected presence of terminal sialic acid linked mostly in α2,6 to GalNAc, Gal terminal or subterminal to sulfates, GalNAc, GlcNAc, and Fuc, mostly linked in α1,6, α1,3 α1,4 and α1,2 to GlcNAc or Gal, but not to lactosamine chains. 27801529 7 20 theme urinary 1454:1460 arg1 bladder 1462:1468 pig urinary bladder 1450:1468 pig urinary bladder 1450:1468 Except for fucosylation, the oligosaccharidic chains in the glycoproteins of the urothelium of pig urinary bladder were similar to those linked to human MUC1, which is fundamental in cell adhesion and immunological processes in the urothelium. 27801529 7 21 from fundamental 1523:1533 arg1 adhesion 1543:1550 cell adhesion 1538:1550 cell adhesion 1538:1550 Except for fucosylation, the oligosaccharidic chains in the glycoproteins of the urothelium of pig urinary bladder were similar to those linked to human MUC1, which is fundamental in cell adhesion and immunological processes in the urothelium. 27801529 7 21 from fundamental 1523:1533 arg1 processes 1570:1578 immunological processes 1556:1578 immunological processes 1556:1578 Except for fucosylation, the oligosaccharidic chains in the glycoproteins of the urothelium of pig urinary bladder were similar to those linked to human MUC1, which is fundamental in cell adhesion and immunological processes in the urothelium. 27801529 5 22 theme sulfated 1016:1023 arg1 glycans 1043:1049 sulfated and/or sialylated glycans 1016:1049 sulfated and/or sialylated glycans 1016:1049 In both superficial and intermediate cells sulfated and/or sialylated glycans were present, sulfation decreasing in the deeper layers. 27801529 1 23 theme bladder 138:144 arg1 urothelium 116:125 the urothelium 112:125 the urothelium of urinary bladder of 10 adult male Landrace pigs 112:175 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 3 24 theme secreting 753:761 arg1 rich 826:829 rich 826:829 rich 826:829 The secreting granules in both intermediate cells and superficial cells were rich in carbohydrates, with the oligosaccharidic chains mostly O-linked to proteins. 27801529 3 24 theme secreting 753:761 arg1 granules 763:770 The secreting granules 749:770 The secreting granules in both intermediate cells and superficial cells 749:819 The secreting granules in both intermediate cells and superficial cells were rich in carbohydrates, with the oligosaccharidic chains mostly O-linked to proteins. 27801529 0 25 theme pig 66:68 arg1 bladder 78:84 pig urinary bladder 66:84 pig urinary bladder 66:84 A histochemical approach to glycan diversity in the urothelium of pig urinary bladder. 27801529 5 26 theme sialylated 1032:1041 arg1 glycans 1043:1049 sulfated and/or sialylated glycans 1016:1049 sulfated and/or sialylated glycans 1016:1049 In both superficial and intermediate cells sulfated and/or sialylated glycans were present, sulfation decreasing in the deeper layers. 27801529 7 27 theme cell 1538:1541 arg1 adhesion 1543:1550 cell adhesion 1538:1550 cell adhesion 1538:1550 Except for fucosylation, the oligosaccharidic chains in the glycoproteins of the urothelium of pig urinary bladder were similar to those linked to human MUC1, which is fundamental in cell adhesion and immunological processes in the urothelium. 27801529 0 28 theme bladder 78:84 arg1 urothelium 52:61 the urothelium 48:61 the urothelium of pig urinary bladder 48:84 A histochemical approach to glycan diversity in the urothelium of pig urinary bladder. 27801529 5 29 theme superficial 981:991 arg1 cells 1010:1014 both superficial and intermediate cells 976:1014 both superficial and intermediate cells 976:1014 In both superficial and intermediate cells sulfated and/or sialylated glycans were present, sulfation decreasing in the deeper layers. 27801529 1 30 dep pre-treatments 520:533 arg1 desulfation 551:561 desulfation 551:561 desulfation 551:561 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 1 30 dep pre-treatments 520:533 arg1 β-elimination 536:548 β-elimination 536:548 β-elimination 536:548 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 1 30 dep pre-treatments 520:533 arg1 pre-treatments 520:533 chemical and enzymatic pre-treatments 497:533 chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) 497:580 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 1 30 dep pre-treatments 520:533 arg1 neuraminidase 567:579 neuraminidase 567:579 neuraminidase 567:579 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 3 31 theme intermediate 780:791 arg1 cells 793:797 intermediate cells 780:797 intermediate cells 780:797 The secreting granules in both intermediate cells and superficial cells were rich in carbohydrates, with the oligosaccharidic chains mostly O-linked to proteins. 27801529 5 32 theme intermediate 997:1008 arg1 cells 1010:1014 both superficial and intermediate cells 976:1014 both superficial and intermediate cells 976:1014 In both superficial and intermediate cells sulfated and/or sialylated glycans were present, sulfation decreasing in the deeper layers. 27801529 5 33 dep present 1056:1062 arg1 decreasing 1075:1084 decreasing 1075:1084 decreasing in the deeper layers 1075:1105 In both superficial and intermediate cells sulfated and/or sialylated glycans were present, sulfation decreasing in the deeper layers. 27801529 6 34 attach linked 1271:1276 arg2 Gal 1198:1200 Gal 1198:1200 Gal terminal or subterminal to sulfates 1198:1236 Lectin-binding detected presence of terminal sialic acid linked mostly in α2,6 to GalNAc, Gal terminal or subterminal to sulfates, GalNAc, GlcNAc, and Fuc, mostly linked in α1,6, α1,3 α1,4 and α1,2 to GlcNAc or Gal, but not to lactosamine chains. 27801529 6 34 attach linked 1271:1276 arg3 α1,6 1281:1284 α1,6 1281:1284 α1,6 1281:1284 Lectin-binding detected presence of terminal sialic acid linked mostly in α2,6 to GalNAc, Gal terminal or subterminal to sulfates, GalNAc, GlcNAc, and Fuc, mostly linked in α1,6, α1,3 α1,4 and α1,2 to GlcNAc or Gal, but not to lactosamine chains. 27801529 5 35 from cells 1010:1014 arg1 present 1056:1062 present 1056:1062 present 1056:1062 In both superficial and intermediate cells sulfated and/or sialylated glycans were present, sulfation decreasing in the deeper layers. 27801529 3 36 theme superficial 803:813 arg1 cells 815:819 superficial cells 803:819 superficial cells 803:819 The secreting granules in both intermediate cells and superficial cells were rich in carbohydrates, with the oligosaccharidic chains mostly O-linked to proteins. 27801529 0 37 theme glycan 28:33 arg1 diversity 35:43 glycan diversity 28:43 glycan diversity in the urothelium of pig urinary bladder 28:84 A histochemical approach to glycan diversity in the urothelium of pig urinary bladder. 27801529 1 38 theme conventional 277:288 arg1 techniques 304:313 conventional histochemical techniques 277:313 conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine) 277:375 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 2 39 located detected 645:652 arg1 layer 720:724 the underlying layer 705:724 the underlying layer of intermediate cells 705:746 Muc1 mucin was detected in the secreting granules of superficial cells and the underlying layer of intermediate cells. 27801529 2 39 located detected 645:652 arg2 mucin 635:639 Muc1 mucin 630:639 Muc1 mucin 630:639 Muc1 mucin was detected in the secreting granules of superficial cells and the underlying layer of intermediate cells. 27801529 2 39 located detected 645:652 arg1 granules 671:678 the secreting granules 657:678 the secreting granules of superficial cells 657:699 Muc1 mucin was detected in the secreting granules of superficial cells and the underlying layer of intermediate cells. 27801529 1 40 theme Periodic-Acid 316:328 arg1 pH 350:351 Alcian Blue pH 2.5 338:355 Alcian Blue pH 2.5 338:355 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 1 40 theme Periodic-Acid 316:328 arg1 Schiff 330:335 Periodic-Acid Schiff 316:335 Periodic-Acid Schiff 316:335 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 1 40 theme Periodic-Acid 316:328 arg1 Diamine 368:374 High-Iron Diamine 358:374 High-Iron Diamine 358:374 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 2 41 theme superficial 683:693 arg1 cells 695:699 superficial cells 683:699 superficial cells 683:699 Muc1 mucin was detected in the secreting granules of superficial cells and the underlying layer of intermediate cells. 27801529 1 42 from glycans 101:107 arg1 urothelium 116:125 the urothelium 112:125 the urothelium of urinary bladder of 10 adult male Landrace pigs 112:175 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 3 43 theme oligosaccharidic 858:873 arg1 chains 875:880 the oligosaccharidic chains 854:880 the oligosaccharidic chains mostly O-linked to proteins 854:908 The secreting granules in both intermediate cells and superficial cells were rich in carbohydrates, with the oligosaccharidic chains mostly O-linked to proteins. 27801529 2 44 theme intermediate 729:740 arg1 cells 742:746 intermediate cells 729:746 intermediate cells 729:746 Muc1 mucin was detected in the secreting granules of superficial cells and the underlying layer of intermediate cells. 27801529 2 45 theme underlying 709:718 arg1 layer 720:724 the underlying layer 705:724 the underlying layer of intermediate cells 705:746 Muc1 mucin was detected in the secreting granules of superficial cells and the underlying layer of intermediate cells. 27801529 1 46 from techniques 304:313 arg1 MUC1 259:262 anti MUC1 254:262 anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal 254:627 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 1 47 theme Muc1 240:243 arg1 mucin 245:249 Muc1 mucin 240:249 Muc1 mucin 240:249 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 1 48 dep SNA 478:480 arg1 ConA 442:445 PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA 407:480 ConA 442:445 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 1 48 dep SNA 478:480 arg1 LTA 460:462 PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA 407:480 LTA 460:462 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 1 48 dep SNA 478:480 arg1 WGA 424:426 PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA 407:480 WGA 424:426 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 1 48 dep SNA 478:480 arg1 LFA 465:467 PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA 407:480 LFA 465:467 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 1 48 dep SNA 478:480 arg1 SBA 429:431 PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA 407:480 SBA 429:431 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 1 48 dep SNA 478:480 arg1 AAA 448:450 PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA 407:480 AAA 448:450 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 1 48 dep SNA 478:480 arg1 DBA 412:414 PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA 407:480 DBA 412:414 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 1 48 dep SNA 478:480 arg1 UEA-I 453:457 PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA 407:480 UEA-I 453:457 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 1 48 dep SNA 478:480 arg1 MAA-II 470:475 PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA 407:480 MAA-II 470:475 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 1 48 dep SNA 478:480 arg1 RCA-I 417:421 PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA 407:480 RCA-I 417:421 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 1 48 dep SNA 478:480 arg1 BSI-B4 434:439 PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA 407:480 BSI-B4 434:439 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 3 49 link O-linked 889:896 arg1 chains 875:880 the oligosaccharidic chains 854:880 the oligosaccharidic chains mostly O-linked to proteins 854:908 The secreting granules in both intermediate cells and superficial cells were rich in carbohydrates, with the oligosaccharidic chains mostly O-linked to proteins. 27801529 7 50 from processes 1570:1578 arg1 fundamental 1523:1533 fundamental 1523:1533 fundamental 1523:1533 Except for fucosylation, the oligosaccharidic chains in the glycoproteins of the urothelium of pig urinary bladder were similar to those linked to human MUC1, which is fundamental in cell adhesion and immunological processes in the urothelium. 27801529 7 50 from processes 1570:1578 arg1 urothelium 1587:1596 the urothelium 1583:1596 the urothelium 1583:1596 Except for fucosylation, the oligosaccharidic chains in the glycoproteins of the urothelium of pig urinary bladder were similar to those linked to human MUC1, which is fundamental in cell adhesion and immunological processes in the urothelium. 27801529 7 51 from adhesion 1543:1550 arg1 fundamental 1523:1533 fundamental 1523:1533 fundamental 1523:1533 Except for fucosylation, the oligosaccharidic chains in the glycoproteins of the urothelium of pig urinary bladder were similar to those linked to human MUC1, which is fundamental in cell adhesion and immunological processes in the urothelium. 27801529 7 51 from adhesion 1543:1550 arg1 urothelium 1587:1596 the urothelium 1583:1596 the urothelium 1583:1596 Except for fucosylation, the oligosaccharidic chains in the glycoproteins of the urothelium of pig urinary bladder were similar to those linked to human MUC1, which is fundamental in cell adhesion and immunological processes in the urothelium. 27801529 5 52 gly sialylated 1032:1041 arg1 glycans 1043:1049 sulfated and/or sialylated glycans 1016:1049 sulfated and/or sialylated glycans 1016:1049 In both superficial and intermediate cells sulfated and/or sialylated glycans were present, sulfation decreasing in the deeper layers. 27801529 1 53 from rabbit 269:274 arg1 MUC1 259:262 anti MUC1 254:262 anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal 254:627 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 7 54 theme immunological 1556:1568 arg1 processes 1570:1578 immunological processes 1556:1578 immunological processes 1556:1578 Except for fucosylation, the oligosaccharidic chains in the glycoproteins of the urothelium of pig urinary bladder were similar to those linked to human MUC1, which is fundamental in cell adhesion and immunological processes in the urothelium. 27801529 1 55 theme adult 152:156 arg1 pigs 172:175 10 adult male Landrace pigs 149:175 10 adult male Landrace pigs 149:175 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 3 56 from granules 763:770 arg1 cells 793:797 intermediate cells 780:797 intermediate cells 780:797 The secreting granules in both intermediate cells and superficial cells were rich in carbohydrates, with the oligosaccharidic chains mostly O-linked to proteins. 27801529 3 56 from granules 763:770 arg1 cells 815:819 superficial cells 803:819 superficial cells 803:819 The secreting granules in both intermediate cells and superficial cells were rich in carbohydrates, with the oligosaccharidic chains mostly O-linked to proteins. 27801529 1 57 theme enzymatic 510:518 arg1 desulfation 551:561 desulfation 551:561 desulfation 551:561 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 1 57 theme enzymatic 510:518 arg1 β-elimination 536:548 β-elimination 536:548 β-elimination 536:548 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 1 57 theme enzymatic 510:518 arg1 pre-treatments 520:533 chemical and enzymatic pre-treatments 497:533 chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) 497:580 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 1 57 theme enzymatic 510:518 arg1 neuraminidase 567:579 neuraminidase 567:579 neuraminidase 567:579 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 1 58 from binding 382:388 arg1 MUC1 259:262 anti MUC1 254:262 anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal 254:627 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 7 59 attach linked 1492:1497 arg1 MUC1 1508:1511 human MUC1 1502:1511 human MUC1 1502:1511 Except for fucosylation, the oligosaccharidic chains in the glycoproteins of the urothelium of pig urinary bladder were similar to those linked to human MUC1, which is fundamental in cell adhesion and immunological processes in the urothelium. 27801529 7 59 attach linked 1492:1497 arg2 those 1486:1490 those 1486:1490 those 1486:1490 Except for fucosylation, the oligosaccharidic chains in the glycoproteins of the urothelium of pig urinary bladder were similar to those linked to human MUC1, which is fundamental in cell adhesion and immunological processes in the urothelium. 27801529 1 60 theme Landrace 163:170 arg1 pigs 172:175 10 adult male Landrace pigs 149:175 10 adult male Landrace pigs 149:175 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 1 61 with MUC1 259:262 arg1 SNA 478:480 PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA 407:480 SNA 478:480 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 1 61 with MUC1 259:262 arg1 lectins 398:404 13 lectins 395:404 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal 395:627 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 7 62 theme bladder 1462:1468 arg1 urothelium 1436:1445 the urothelium 1432:1445 the urothelium of pig urinary bladder 1432:1468 Except for fucosylation, the oligosaccharidic chains in the glycoproteins of the urothelium of pig urinary bladder were similar to those linked to human MUC1, which is fundamental in cell adhesion and immunological processes in the urothelium. 27801529 6 63 theme terminal 1144:1151 arg1 acid 1160:1163 terminal sialic acid 1144:1163 terminal sialic acid linked mostly in α2,6 to GalNAc, Gal terminal or subterminal to sulfates, GalNAc, GlcNAc, and Fuc, mostly linked in α1,6, α1,3 α1,4 and α1,2 to GlcNAc or Gal, but not to lactosamine chains 1144:1352 Lectin-binding detected presence of terminal sialic acid linked mostly in α2,6 to GalNAc, Gal terminal or subterminal to sulfates, GalNAc, GlcNAc, and Fuc, mostly linked in α1,6, α1,3 α1,4 and α1,2 to GlcNAc or Gal, but not to lactosamine chains. 27801529 6 64 theme subterminal 1214:1224 arg1 Gal 1198:1200 Gal 1198:1200 Gal terminal or subterminal to sulfates 1198:1236 Lectin-binding detected presence of terminal sialic acid linked mostly in α2,6 to GalNAc, Gal terminal or subterminal to sulfates, GalNAc, GlcNAc, and Fuc, mostly linked in α1,6, α1,3 α1,4 and α1,2 to GlcNAc or Gal, but not to lactosamine chains. 27801529 7 65 theme pig 1450:1452 arg1 bladder 1462:1468 pig urinary bladder 1450:1468 pig urinary bladder 1450:1468 Except for fucosylation, the oligosaccharidic chains in the glycoproteins of the urothelium of pig urinary bladder were similar to those linked to human MUC1, which is fundamental in cell adhesion and immunological processes in the urothelium. 27801529 6 66 theme terminal 1202:1209 arg1 Gal 1198:1200 Gal 1198:1200 Gal terminal or subterminal to sulfates 1198:1236 Lectin-binding detected presence of terminal sialic acid linked mostly in α2,6 to GalNAc, Gal terminal or subterminal to sulfates, GalNAc, GlcNAc, and Fuc, mostly linked in α1,6, α1,3 α1,4 and α1,2 to GlcNAc or Gal, but not to lactosamine chains. 27801529 7 67 theme urothelium 1436:1445 arg1 glycoproteins 1415:1427 the glycoproteins 1411:1427 the glycoproteins of the urothelium of pig urinary bladder 1411:1468 Except for fucosylation, the oligosaccharidic chains in the glycoproteins of the urothelium of pig urinary bladder were similar to those linked to human MUC1, which is fundamental in cell adhesion and immunological processes in the urothelium. 27801529 8 68 theme Muc1 1622:1625 arg1 co-distribution 1603:1617 The co-distribution 1599:1617 The co-distribution of Muc1 and saccharidic residues 1599:1650 The co-distribution of Muc1 and saccharidic residues suggests that many of them are linked to the glycoprotein. 27801529 1 69 theme urinary 130:136 arg1 bladder 138:144 urinary bladder 130:144 urinary bladder of 10 adult male Landrace pigs 130:175 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 0 70 theme urinary 70:76 arg1 bladder 78:84 pig urinary bladder 66:84 pig urinary bladder 66:84 A histochemical approach to glycan diversity in the urothelium of pig urinary bladder. 27801529 8 71 theme saccharidic 1631:1641 arg1 co-distribution 1603:1617 The co-distribution 1599:1617 The co-distribution of Muc1 and saccharidic residues 1599:1650 The co-distribution of Muc1 and saccharidic residues suggests that many of them are linked to the glycoprotein. 27801529 1 72 theme Blue 345:348 arg1 pH 350:351 Alcian Blue pH 2.5 338:355 Alcian Blue pH 2.5 338:355 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 1 72 theme Blue 345:348 arg1 Schiff 330:335 Periodic-Acid Schiff 316:335 Periodic-Acid Schiff 316:335 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 1 73 theme chemical 497:504 arg1 desulfation 551:561 desulfation 551:561 desulfation 551:561 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 1 73 theme chemical 497:504 arg1 β-elimination 536:548 β-elimination 536:548 β-elimination 536:548 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 1 73 theme chemical 497:504 arg1 pre-treatments 520:533 chemical and enzymatic pre-treatments 497:533 chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) 497:580 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 1 73 theme chemical 497:504 arg1 neuraminidase 567:579 neuraminidase 567:579 neuraminidase 567:579 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 1 74 theme Alcian 338:343 arg1 pH 350:351 Alcian Blue pH 2.5 338:355 Alcian Blue pH 2.5 338:355 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 1 74 theme Alcian 338:343 arg1 Schiff 330:335 Periodic-Acid Schiff 316:335 Periodic-Acid Schiff 316:335 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 1 75 dep techniques 304:313 arg1 pH 350:351 Alcian Blue pH 2.5 338:355 Alcian Blue pH 2.5 338:355 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 1 75 dep techniques 304:313 arg1 Schiff 330:335 Periodic-Acid Schiff 316:335 Periodic-Acid Schiff 316:335 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 1 75 dep techniques 304:313 arg1 Diamine 368:374 High-Iron Diamine 358:374 High-Iron Diamine 358:374 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 0 76 from diversity 35:43 arg1 urothelium 52:61 the urothelium 48:61 the urothelium of pig urinary bladder 48:84 A histochemical approach to glycan diversity in the urothelium of pig urinary bladder. 27801529 0 77 theme histochemical 2:14 arg1 approach 16:23 A histochemical approach 0:23 A histochemical approach to glycan diversity in the urothelium of pig urinary bladder 0:84 A histochemical approach to glycan diversity in the urothelium of pig urinary bladder. 27801529 8 78 theme them 1674:1677 arg1 many 1666:1669 many 1666:1669 many 1666:1669 The co-distribution of Muc1 and saccharidic residues suggests that many of them are linked to the glycoprotein. 27801529 8 78 theme them 1674:1677 arg1 them 1674:1677 them 1674:1677 them 1674:1677 The co-distribution of Muc1 and saccharidic residues suggests that many of them are linked to the glycoprotein. 27801529 5 79 located present 1056:1062 arg2 glycans 1043:1049 sulfated and/or sialylated glycans 1016:1049 sulfated and/or sialylated glycans 1016:1049 In both superficial and intermediate cells sulfated and/or sialylated glycans were present, sulfation decreasing in the deeper layers. 27801529 5 79 located present 1056:1062 arg1 cells 1010:1014 both superficial and intermediate cells 976:1014 both superficial and intermediate cells 976:1014 In both superficial and intermediate cells sulfated and/or sialylated glycans were present, sulfation decreasing in the deeper layers. 27801529 7 80 from chains 1401:1406 arg1 glycoproteins 1415:1427 the glycoproteins 1411:1427 the glycoproteins of the urothelium of pig urinary bladder 1411:1468 Except for fucosylation, the oligosaccharidic chains in the glycoproteins of the urothelium of pig urinary bladder were similar to those linked to human MUC1, which is fundamental in cell adhesion and immunological processes in the urothelium. 27801529 1 81 theme Intracellular 87:99 arg1 glycans 101:107 Intracellular glycans 87:107 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs 87:175 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 3 82 from rich 826:829 arg1 carbohydrates 834:846 carbohydrates 834:846 carbohydrates 834:846 The secreting granules in both intermediate cells and superficial cells were rich in carbohydrates, with the oligosaccharidic chains mostly O-linked to proteins. 27801529 6 83 theme α1,3 1287:1290 arg1 α1,4 1292:1295 α1,3 α1,4 1287:1295 α1,3 α1,4 1287:1295 Lectin-binding detected presence of terminal sialic acid linked mostly in α2,6 to GalNAc, Gal terminal or subterminal to sulfates, GalNAc, GlcNAc, and Fuc, mostly linked in α1,6, α1,3 α1,4 and α1,2 to GlcNAc or Gal, but not to lactosamine chains. 27801529 5 84 theme deeper 1093:1098 arg1 layers 1100:1105 the deeper layers 1089:1105 the deeper layers 1089:1105 In both superficial and intermediate cells sulfated and/or sialylated glycans were present, sulfation decreasing in the deeper layers. 27801529 7 85 theme oligosaccharidic 1384:1399 arg1 chains 1401:1406 the oligosaccharidic chains 1380:1406 the oligosaccharidic chains in the glycoproteins of the urothelium of pig urinary bladder 1380:1468 Except for fucosylation, the oligosaccharidic chains in the glycoproteins of the urothelium of pig urinary bladder were similar to those linked to human MUC1, which is fundamental in cell adhesion and immunological processes in the urothelium. 27801529 7 85 theme oligosaccharidic 1384:1399 arg1 similar 1475:1481 similar 1475:1481 similar 1475:1481 Except for fucosylation, the oligosaccharidic chains in the glycoproteins of the urothelium of pig urinary bladder were similar to those linked to human MUC1, which is fundamental in cell adhesion and immunological processes in the urothelium. 27801529 7 86 theme human 1502:1506 arg1 MUC1 1508:1511 human MUC1 1502:1511 human MUC1 1502:1511 Except for fucosylation, the oligosaccharidic chains in the glycoproteins of the urothelium of pig urinary bladder were similar to those linked to human MUC1, which is fundamental in cell adhesion and immunological processes in the urothelium. 27801529 3 87 from carbohydrates 834:846 arg1 rich 826:829 rich 826:829 rich 826:829 The secreting granules in both intermediate cells and superficial cells were rich in carbohydrates, with the oligosaccharidic chains mostly O-linked to proteins. 27801529 3 87 from carbohydrates 834:846 arg1 granules 763:770 The secreting granules 749:770 The secreting granules in both intermediate cells and superficial cells 749:819 The secreting granules in both intermediate cells and superficial cells were rich in carbohydrates, with the oligosaccharidic chains mostly O-linked to proteins. 27801529 8 88 dep Muc1 1622:1625 arg1 residues 1643:1650 residues 1643:1650 residues 1643:1650 The co-distribution of Muc1 and saccharidic residues suggests that many of them are linked to the glycoprotein. 27801529 1 89 theme histochemical 290:302 arg1 techniques 304:313 conventional histochemical techniques 277:313 conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine) 277:375 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 6 90 dep GlcNAc 1309:1314 arg1 to 1306:1307 to 1306:1307 to 1306:1307 Lectin-binding detected presence of terminal sialic acid linked mostly in α2,6 to GalNAc, Gal terminal or subterminal to sulfates, GalNAc, GlcNAc, and Fuc, mostly linked in α1,6, α1,3 α1,4 and α1,2 to GlcNAc or Gal, but not to lactosamine chains. 27801529 6 91 theme lactosamine 1335:1345 arg1 chains 1347:1352 lactosamine chains 1335:1352 lactosamine chains 1335:1352 Lectin-binding detected presence of terminal sialic acid linked mostly in α2,6 to GalNAc, Gal terminal or subterminal to sulfates, GalNAc, GlcNAc, and Fuc, mostly linked in α1,6, α1,3 α1,4 and α1,2 to GlcNAc or Gal, but not to lactosamine chains. 27801529 8 92 gly glycoprotein 1697:1708 arg1 glycoprotein 1697:1708 the glycoprotein 1693:1708 the glycoprotein 1693:1708 The co-distribution of Muc1 and saccharidic residues suggests that many of them are linked to the glycoprotein. 27801529 2 93 theme cells 742:746 arg1 layer 720:724 the underlying layer 705:724 the underlying layer of intermediate cells 705:746 Muc1 mucin was detected in the secreting granules of superficial cells and the underlying layer of intermediate cells. 27801529 2 93 theme cells 742:746 arg1 granules 671:678 the secreting granules 657:678 the secreting granules of superficial cells 657:699 Muc1 mucin was detected in the secreting granules of superficial cells and the underlying layer of intermediate cells. 27801529 1 94 theme immunohistochemical 207:225 arg1 detection 227:235 immunohistochemical detection 207:235 immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal 207:627 Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. 27801529 2 95 theme secreting 661:669 arg1 granules 671:678 the secreting granules 657:678 the secreting granules of superficial cells 657:699 Muc1 mucin was detected in the secreting granules of superficial cells and the underlying layer of intermediate cells. 26735314 3 0 contain contained 490:498 arg2 CD4 514:516 the ovalbumin CD4 500:516 the ovalbumin CD4 500:516 In the present study, a library of vaccine constructs comprising fluorescently labeled mannosylated lipid-dendrimers that contained the ovalbumin CD4(+) epitope, OVA(323-339), as the model peptide antigen were synthesized using fluorenylmethyloxycarbonyl (Fmoc) solid phase peptide synthesis (SPPS). 26735314 3 0 contain contained 490:498 arg2 antigen 565:571 the model peptide antigen 547:571 the model peptide antigen 547:571 In the present study, a library of vaccine constructs comprising fluorescently labeled mannosylated lipid-dendrimers that contained the ovalbumin CD4(+) epitope, OVA(323-339), as the model peptide antigen were synthesized using fluorenylmethyloxycarbonyl (Fmoc) solid phase peptide synthesis (SPPS). 26735314 3 0 contain contained 490:498 arg2 epitope 521:527 epitope 521:527 epitope 521:527 In the present study, a library of vaccine constructs comprising fluorescently labeled mannosylated lipid-dendrimers that contained the ovalbumin CD4(+) epitope, OVA(323-339), as the model peptide antigen were synthesized using fluorenylmethyloxycarbonyl (Fmoc) solid phase peptide synthesis (SPPS). 26735314 3 0 contain contained 490:498 arg1 lipid-dendrimers 468:483 fluorescently labeled mannosylated lipid-dendrimers 433:483 fluorescently labeled mannosylated lipid-dendrimers that contained the ovalbumin CD4(+) epitope, OVA(323-339), as the model peptide antigen 433:571 In the present study, a library of vaccine constructs comprising fluorescently labeled mannosylated lipid-dendrimers that contained the ovalbumin CD4(+) epitope, OVA(323-339), as the model peptide antigen were synthesized using fluorenylmethyloxycarbonyl (Fmoc) solid phase peptide synthesis (SPPS). 26735314 3 0 contain contained 490:498 arg2 OVA 530:532 OVA 530:532 OVA 530:532 In the present study, a library of vaccine constructs comprising fluorescently labeled mannosylated lipid-dendrimers that contained the ovalbumin CD4(+) epitope, OVA(323-339), as the model peptide antigen were synthesized using fluorenylmethyloxycarbonyl (Fmoc) solid phase peptide synthesis (SPPS). 26735314 3 0 contain contained 490:498 arg2 323-339 534:540 323-339 534:540 323-339 534:540 In the present study, a library of vaccine constructs comprising fluorescently labeled mannosylated lipid-dendrimers that contained the ovalbumin CD4(+) epitope, OVA(323-339), as the model peptide antigen were synthesized using fluorenylmethyloxycarbonyl (Fmoc) solid phase peptide synthesis (SPPS). 26735314 6 1 dep mediated 1280:1287 arg1 receptor 1271:1278 receptor 1271:1278 receptor 1271:1278 Furthermore, mannan inhibition assays demonstrated that uptake of the mannosylated and lipidated peptides was receptor mediated. 26735314 1 2 theme mannose 138:144 arg1 receptor 201:208 a front-line receptor 188:208 a front-line receptor in pathogen recognition 188:232 Present on the surface of antigen presenting cells (APCs), the mannose receptor (MR) has long been recognized as a front-line receptor in pathogen recognition. 26735314 1 2 theme mannose 138:144 arg1 MR 156:157 MR 156:157 MR 156:157 Present on the surface of antigen presenting cells (APCs), the mannose receptor (MR) has long been recognized as a front-line receptor in pathogen recognition. 26735314 1 2 theme mannose 138:144 arg1 receptor 146:153 the mannose receptor 134:153 the mannose receptor (MR) 134:158 Present on the surface of antigen presenting cells (APCs), the mannose receptor (MR) has long been recognized as a front-line receptor in pathogen recognition. 26735314 6 3 theme mannosylated 1231:1242 arg1 peptides 1258:1265 the mannosylated and lipidated peptides 1227:1265 the mannosylated and lipidated peptides 1227:1265 Furthermore, mannan inhibition assays demonstrated that uptake of the mannosylated and lipidated peptides was receptor mediated. 26735314 1 4 theme pathogen 213:220 arg1 recognition 222:232 pathogen recognition 213:232 pathogen recognition 213:232 Present on the surface of antigen presenting cells (APCs), the mannose receptor (MR) has long been recognized as a front-line receptor in pathogen recognition. 26735314 3 5 theme peptide 642:648 arg1 SPPS 661:664 SPPS 661:664 SPPS 661:664 In the present study, a library of vaccine constructs comprising fluorescently labeled mannosylated lipid-dendrimers that contained the ovalbumin CD4(+) epitope, OVA(323-339), as the model peptide antigen were synthesized using fluorenylmethyloxycarbonyl (Fmoc) solid phase peptide synthesis (SPPS). 26735314 3 5 theme peptide 642:648 arg1 synthesis 650:658 fluorenylmethyloxycarbonyl (Fmoc) solid phase peptide synthesis 596:658 fluorenylmethyloxycarbonyl (Fmoc) solid phase peptide synthesis (SPPS) 596:665 In the present study, a library of vaccine constructs comprising fluorescently labeled mannosylated lipid-dendrimers that contained the ovalbumin CD4(+) epitope, OVA(323-339), as the model peptide antigen were synthesized using fluorenylmethyloxycarbonyl (Fmoc) solid phase peptide synthesis (SPPS). 26735314 4 6 theme mannose 816:822 arg1 units 824:828 the mannose units 812:828 the mannose units 812:828 The vaccine constructs were designed with an alanine spacer between the O-linked mannose moieties to investigate the impact of distance between the mannose units on receptor-mediated uptake and/or binding in APCs. 26735314 7 7 theme vaccine 1473:1479 arg1 constructs 1481:1490 the mannosylated and lipidated vaccine constructs 1442:1490 the mannosylated and lipidated vaccine constructs 1442:1490 To address the specificity of receptor uptake, surface plasmon resonance studies were performed using biacore technology and confirmed high affinity of the mannosylated and lipidated vaccine constructs toward the MR. These studies confirm that both mannose and lipid moieties play significant roles in receptor-mediated uptake on APCs, potentially facilitating vaccine development. 26735314 7 8 theme constructs 1481:1490 arg1 affinity 1430:1437 high affinity 1425:1437 high affinity of the mannosylated and lipidated vaccine constructs toward the MR. These studies confirm that both mannose and lipid moieties play significant roles in receptor-mediated uptake on APCs, potentially facilitating vaccine development 1425:1669 To address the specificity of receptor uptake, surface plasmon resonance studies were performed using biacore technology and confirmed high affinity of the mannosylated and lipidated vaccine constructs toward the MR. These studies confirm that both mannose and lipid moieties play significant roles in receptor-mediated uptake on APCs, potentially facilitating vaccine development. 26735314 7 9 dep MR. 1503:1505 arg1 confirm 1521:1527 confirm 1521:1527 confirm that both mannose and lipid moieties play significant roles in receptor-mediated uptake on APCs, potentially facilitating vaccine development 1521:1669 To address the specificity of receptor uptake, surface plasmon resonance studies were performed using biacore technology and confirmed high affinity of the mannosylated and lipidated vaccine constructs toward the MR. These studies confirm that both mannose and lipid moieties play significant roles in receptor-mediated uptake on APCs, potentially facilitating vaccine development. 26735314 4 10 theme receptor-mediated 833:849 arg1 uptake 851:856 receptor-mediated uptake 833:856 receptor-mediated uptake 833:856 The vaccine constructs were designed with an alanine spacer between the O-linked mannose moieties to investigate the impact of distance between the mannose units on receptor-mediated uptake and/or binding in APCs. 26735314 5 11 with peptide 1096:1102 arg1 lipid 1112:1116 lipid 1112:1116 lipid 1112:1116 Uptake studies performed on F4/80(+) and CD11c(+) cells showed significant uptake and/or binding for lipopeptides containing mannose, and also the lipopeptide without mannose when compared to the control peptides (peptide with no lipid and peptide with no mannose and no lipid). 26735314 5 11 with peptide 1096:1102 arg1 peptide 1122:1128 peptide 1122:1128 peptide 1122:1128 Uptake studies performed on F4/80(+) and CD11c(+) cells showed significant uptake and/or binding for lipopeptides containing mannose, and also the lipopeptide without mannose when compared to the control peptides (peptide with no lipid and peptide with no mannose and no lipid). 26735314 5 11 with peptide 1096:1102 arg1 lipid 1153:1157 no lipid 1150:1157 no lipid 1150:1157 Uptake studies performed on F4/80(+) and CD11c(+) cells showed significant uptake and/or binding for lipopeptides containing mannose, and also the lipopeptide without mannose when compared to the control peptides (peptide with no lipid and peptide with no mannose and no lipid). 26735314 4 12 theme alanine 713:719 arg1 spacer 721:726 an alanine spacer 710:726 an alanine spacer between the O-linked mannose moieties 710:764 The vaccine constructs were designed with an alanine spacer between the O-linked mannose moieties to investigate the impact of distance between the mannose units on receptor-mediated uptake and/or binding in APCs. 26735314 7 13 theme uptake 1329:1334 arg1 specificity 1305:1315 the specificity 1301:1315 the specificity of receptor uptake 1301:1334 To address the specificity of receptor uptake, surface plasmon resonance studies were performed using biacore technology and confirmed high affinity of the mannosylated and lipidated vaccine constructs toward the MR. These studies confirm that both mannose and lipid moieties play significant roles in receptor-mediated uptake on APCs, potentially facilitating vaccine development. 26735314 7 14 theme biacore 1392:1398 arg1 technology 1400:1409 biacore technology 1392:1409 biacore technology 1392:1409 To address the specificity of receptor uptake, surface plasmon resonance studies were performed using biacore technology and confirmed high affinity of the mannosylated and lipidated vaccine constructs toward the MR. These studies confirm that both mannose and lipid moieties play significant roles in receptor-mediated uptake on APCs, potentially facilitating vaccine development. 26735314 6 15 theme inhibition 1181:1190 arg1 assays 1192:1197 mannan inhibition assays 1174:1197 mannan inhibition assays 1174:1197 Furthermore, mannan inhibition assays demonstrated that uptake of the mannosylated and lipidated peptides was receptor mediated. 26735314 5 16 contain containing 996:1005 arg1 lipopeptides 983:994 lipopeptides 983:994 lipopeptides containing mannose, and also the lipopeptide without mannose 983:1055 Uptake studies performed on F4/80(+) and CD11c(+) cells showed significant uptake and/or binding for lipopeptides containing mannose, and also the lipopeptide without mannose when compared to the control peptides (peptide with no lipid and peptide with no mannose and no lipid). 26735314 5 16 contain containing 996:1005 arg2 mannose 1007:1013 mannose 1007:1013 mannose 1007:1013 Uptake studies performed on F4/80(+) and CD11c(+) cells showed significant uptake and/or binding for lipopeptides containing mannose, and also the lipopeptide without mannose when compared to the control peptides (peptide with no lipid and peptide with no mannose and no lipid). 26735314 5 16 contain containing 996:1005 arg2 lipopeptide 1029:1039 the lipopeptide 1025:1039 the lipopeptide without mannose 1025:1055 Uptake studies performed on F4/80(+) and CD11c(+) cells showed significant uptake and/or binding for lipopeptides containing mannose, and also the lipopeptide without mannose when compared to the control peptides (peptide with no lipid and peptide with no mannose and no lipid). 26735314 2 17 dep many 258:261 arg1 attempts 263:270 attempts 263:270 attempts 263:270 During the past decade many attempts have been made to target this receptor for applications including vaccine and drug development. 26735314 7 18 theme vaccine 1651:1657 arg1 development 1659:1669 vaccine development 1651:1669 vaccine development 1651:1669 To address the specificity of receptor uptake, surface plasmon resonance studies were performed using biacore technology and confirmed high affinity of the mannosylated and lipidated vaccine constructs toward the MR. These studies confirm that both mannose and lipid moieties play significant roles in receptor-mediated uptake on APCs, potentially facilitating vaccine development. 26735314 4 19 theme distance 795:802 arg1 impact 785:790 the impact 781:790 the impact of distance between the mannose units on receptor-mediated uptake and/or binding in APCs 781:879 The vaccine constructs were designed with an alanine spacer between the O-linked mannose moieties to investigate the impact of distance between the mannose units on receptor-mediated uptake and/or binding in APCs. 26735314 2 20 theme past 246:249 arg1 decade 251:256 the past decade 242:256 the past decade 242:256 During the past decade many attempts have been made to target this receptor for applications including vaccine and drug development. 26735314 5 21 theme Uptake 882:887 arg1 studies 889:895 Uptake studies 882:895 Uptake studies performed on F4/80(+) and CD11c(+) cells 882:936 Uptake studies performed on F4/80(+) and CD11c(+) cells showed significant uptake and/or binding for lipopeptides containing mannose, and also the lipopeptide without mannose when compared to the control peptides (peptide with no lipid and peptide with no mannose and no lipid). 26735314 7 22 theme lipid 1551:1555 arg1 moieties 1557:1564 both mannose and lipid moieties 1534:1564 moieties 1557:1564 To address the specificity of receptor uptake, surface plasmon resonance studies were performed using biacore technology and confirmed high affinity of the mannosylated and lipidated vaccine constructs toward the MR. These studies confirm that both mannose and lipid moieties play significant roles in receptor-mediated uptake on APCs, potentially facilitating vaccine development. 26735314 3 23 theme present 375:381 arg1 study 383:387 the present study 371:387 the present study 371:387 In the present study, a library of vaccine constructs comprising fluorescently labeled mannosylated lipid-dendrimers that contained the ovalbumin CD4(+) epitope, OVA(323-339), as the model peptide antigen were synthesized using fluorenylmethyloxycarbonyl (Fmoc) solid phase peptide synthesis (SPPS). 26735314 5 24 with lipid 1112:1116 arg1 mannose 1138:1144 no mannose 1135:1144 no mannose 1135:1144 Uptake studies performed on F4/80(+) and CD11c(+) cells showed significant uptake and/or binding for lipopeptides containing mannose, and also the lipopeptide without mannose when compared to the control peptides (peptide with no lipid and peptide with no mannose and no lipid). 26735314 5 25 theme CD11c 923:927 arg1 cells 932:936 F4/80(+) and CD11c(+) cells 910:936 F4/80(+) and CD11c(+) cells 910:936 Uptake studies performed on F4/80(+) and CD11c(+) cells showed significant uptake and/or binding for lipopeptides containing mannose, and also the lipopeptide without mannose when compared to the control peptides (peptide with no lipid and peptide with no mannose and no lipid). 26735314 6 26 gly mannosylated 1231:1242 arg1 peptides 1258:1265 the mannosylated and lipidated peptides 1227:1265 the mannosylated and lipidated peptides 1227:1265 Furthermore, mannan inhibition assays demonstrated that uptake of the mannosylated and lipidated peptides was receptor mediated. 26735314 5 27 dep peptides 1086:1093 arg1 peptide 1096:1102 peptide 1096:1102 peptide 1096:1102 Uptake studies performed on F4/80(+) and CD11c(+) cells showed significant uptake and/or binding for lipopeptides containing mannose, and also the lipopeptide without mannose when compared to the control peptides (peptide with no lipid and peptide with no mannose and no lipid). 26735314 5 28 theme F4/80 910:914 arg1 cells 932:936 F4/80(+) and CD11c(+) cells 910:936 F4/80(+) and CD11c(+) cells 910:936 Uptake studies performed on F4/80(+) and CD11c(+) cells showed significant uptake and/or binding for lipopeptides containing mannose, and also the lipopeptide without mannose when compared to the control peptides (peptide with no lipid and peptide with no mannose and no lipid). 26735314 2 29 theme drug 350:353 arg1 development 355:365 drug development 350:365 drug development 350:365 During the past decade many attempts have been made to target this receptor for applications including vaccine and drug development. 26735314 6 30 theme mannan 1174:1179 arg1 assays 1192:1197 mannan inhibition assays 1174:1197 mannan inhibition assays 1174:1197 Furthermore, mannan inhibition assays demonstrated that uptake of the mannosylated and lipidated peptides was receptor mediated. 26735314 7 31 theme mannosylated 1446:1457 arg1 constructs 1481:1490 the mannosylated and lipidated vaccine constructs 1442:1490 the mannosylated and lipidated vaccine constructs 1442:1490 To address the specificity of receptor uptake, surface plasmon resonance studies were performed using biacore technology and confirmed high affinity of the mannosylated and lipidated vaccine constructs toward the MR. These studies confirm that both mannose and lipid moieties play significant roles in receptor-mediated uptake on APCs, potentially facilitating vaccine development. 26735314 0 32 theme Lipopeptides 26:37 arg1 Synthesis 0:8 Synthesis 0:8 Synthesis of Mannosylated Lipopeptides with Receptor Targeting Properties. 0:73 Synthesis of Mannosylated Lipopeptides with Receptor Targeting Properties. 26735314 7 33 theme surface 1337:1343 arg1 resonance 1353:1361 surface plasmon resonance 1337:1361 surface plasmon resonance studies 1337:1369 To address the specificity of receptor uptake, surface plasmon resonance studies were performed using biacore technology and confirmed high affinity of the mannosylated and lipidated vaccine constructs toward the MR. These studies confirm that both mannose and lipid moieties play significant roles in receptor-mediated uptake on APCs, potentially facilitating vaccine development. 26735314 3 34 gly mannosylated 455:466 arg1 lipid-dendrimers 468:483 fluorescently labeled mannosylated lipid-dendrimers 433:483 fluorescently labeled mannosylated lipid-dendrimers that contained the ovalbumin CD4(+) epitope, OVA(323-339), as the model peptide antigen 433:571 In the present study, a library of vaccine constructs comprising fluorescently labeled mannosylated lipid-dendrimers that contained the ovalbumin CD4(+) epitope, OVA(323-339), as the model peptide antigen were synthesized using fluorenylmethyloxycarbonyl (Fmoc) solid phase peptide synthesis (SPPS). 26735314 7 35 theme receptor-mediated 1592:1608 arg1 uptake 1610:1615 receptor-mediated uptake 1592:1615 receptor-mediated uptake on APCs 1592:1623 To address the specificity of receptor uptake, surface plasmon resonance studies were performed using biacore technology and confirmed high affinity of the mannosylated and lipidated vaccine constructs toward the MR. These studies confirm that both mannose and lipid moieties play significant roles in receptor-mediated uptake on APCs, potentially facilitating vaccine development. 26735314 0 36 theme Mannosylated 13:24 arg1 Lipopeptides 26:37 Mannosylated Lipopeptides 13:37 Mannosylated Lipopeptides 13:37 Synthesis of Mannosylated Lipopeptides with Receptor Targeting Properties. 26735314 7 37 theme significant 1571:1581 arg1 roles 1583:1587 significant roles 1571:1587 significant roles 1571:1587 To address the specificity of receptor uptake, surface plasmon resonance studies were performed using biacore technology and confirmed high affinity of the mannosylated and lipidated vaccine constructs toward the MR. These studies confirm that both mannose and lipid moieties play significant roles in receptor-mediated uptake on APCs, potentially facilitating vaccine development. 26735314 6 38 theme peptides 1258:1265 arg1 uptake 1217:1222 uptake 1217:1222 uptake of the mannosylated and lipidated peptides 1217:1265 Furthermore, mannan inhibition assays demonstrated that uptake of the mannosylated and lipidated peptides was receptor mediated. 26735314 3 39 theme fluorenylmethyloxycarbonyl 596:621 arg1 SPPS 661:664 SPPS 661:664 SPPS 661:664 In the present study, a library of vaccine constructs comprising fluorescently labeled mannosylated lipid-dendrimers that contained the ovalbumin CD4(+) epitope, OVA(323-339), as the model peptide antigen were synthesized using fluorenylmethyloxycarbonyl (Fmoc) solid phase peptide synthesis (SPPS). 26735314 3 39 theme fluorenylmethyloxycarbonyl 596:621 arg1 synthesis 650:658 fluorenylmethyloxycarbonyl (Fmoc) solid phase peptide synthesis 596:658 fluorenylmethyloxycarbonyl (Fmoc) solid phase peptide synthesis (SPPS) 596:665 In the present study, a library of vaccine constructs comprising fluorescently labeled mannosylated lipid-dendrimers that contained the ovalbumin CD4(+) epitope, OVA(323-339), as the model peptide antigen were synthesized using fluorenylmethyloxycarbonyl (Fmoc) solid phase peptide synthesis (SPPS). 26735314 1 40 theme presenting 109:118 arg1 APCs 127:130 APCs 127:130 APCs 127:130 Present on the surface of antigen presenting cells (APCs), the mannose receptor (MR) has long been recognized as a front-line receptor in pathogen recognition. 26735314 1 40 theme presenting 109:118 arg1 cells 120:124 antigen presenting cells 101:124 antigen presenting cells (APCs) 101:131 Present on the surface of antigen presenting cells (APCs), the mannose receptor (MR) has long been recognized as a front-line receptor in pathogen recognition. 26735314 7 41 theme plasmon 1345:1351 arg1 resonance 1353:1361 surface plasmon resonance 1337:1361 surface plasmon resonance studies 1337:1369 To address the specificity of receptor uptake, surface plasmon resonance studies were performed using biacore technology and confirmed high affinity of the mannosylated and lipidated vaccine constructs toward the MR. These studies confirm that both mannose and lipid moieties play significant roles in receptor-mediated uptake on APCs, potentially facilitating vaccine development. 26735314 0 42 theme Receptor 44:51 arg1 Properties 63:72 Receptor Targeting Properties 44:72 Receptor Targeting Properties 44:72 Synthesis of Mannosylated Lipopeptides with Receptor Targeting Properties. 26735314 6 43 theme lipidated 1248:1256 arg1 peptides 1258:1265 the mannosylated and lipidated peptides 1227:1265 the mannosylated and lipidated peptides 1227:1265 Furthermore, mannan inhibition assays demonstrated that uptake of the mannosylated and lipidated peptides was receptor mediated. 26735314 4 44 link O-linked 740:747 arg1 moieties 757:764 the O-linked mannose moieties 736:764 the O-linked mannose moieties 736:764 The vaccine constructs were designed with an alanine spacer between the O-linked mannose moieties to investigate the impact of distance between the mannose units on receptor-mediated uptake and/or binding in APCs. 26735314 7 45 from uptake 1610:1615 arg1 APCs 1620:1623 APCs 1620:1623 APCs 1620:1623 To address the specificity of receptor uptake, surface plasmon resonance studies were performed using biacore technology and confirmed high affinity of the mannosylated and lipidated vaccine constructs toward the MR. These studies confirm that both mannose and lipid moieties play significant roles in receptor-mediated uptake on APCs, potentially facilitating vaccine development. 26735314 3 46 theme vaccine 403:409 arg1 constructs 411:420 vaccine constructs 403:420 vaccine constructs comprising fluorescently labeled mannosylated lipid-dendrimers that contained the ovalbumin CD4(+) epitope, OVA(323-339), as the model peptide antigen 403:571 In the present study, a library of vaccine constructs comprising fluorescently labeled mannosylated lipid-dendrimers that contained the ovalbumin CD4(+) epitope, OVA(323-339), as the model peptide antigen were synthesized using fluorenylmethyloxycarbonyl (Fmoc) solid phase peptide synthesis (SPPS). 26735314 5 47 theme control 1078:1084 arg1 peptides 1086:1093 the control peptides 1074:1093 the control peptides (peptide with no lipid and peptide with no mannose and no lipid) 1074:1158 Uptake studies performed on F4/80(+) and CD11c(+) cells showed significant uptake and/or binding for lipopeptides containing mannose, and also the lipopeptide without mannose when compared to the control peptides (peptide with no lipid and peptide with no mannose and no lipid). 26735314 7 48 theme receptor 1320:1327 arg1 uptake 1329:1334 receptor uptake 1320:1334 receptor uptake 1320:1334 To address the specificity of receptor uptake, surface plasmon resonance studies were performed using biacore technology and confirmed high affinity of the mannosylated and lipidated vaccine constructs toward the MR. These studies confirm that both mannose and lipid moieties play significant roles in receptor-mediated uptake on APCs, potentially facilitating vaccine development. 26735314 7 49 theme lipidated 1463:1471 arg1 constructs 1481:1490 the mannosylated and lipidated vaccine constructs 1442:1490 the mannosylated and lipidated vaccine constructs 1442:1490 To address the specificity of receptor uptake, surface plasmon resonance studies were performed using biacore technology and confirmed high affinity of the mannosylated and lipidated vaccine constructs toward the MR. These studies confirm that both mannose and lipid moieties play significant roles in receptor-mediated uptake on APCs, potentially facilitating vaccine development. 26735314 5 50 theme significant 945:955 arg1 uptake 957:962 significant uptake 945:962 significant uptake 945:962 Uptake studies performed on F4/80(+) and CD11c(+) cells showed significant uptake and/or binding for lipopeptides containing mannose, and also the lipopeptide without mannose when compared to the control peptides (peptide with no lipid and peptide with no mannose and no lipid). 26735314 4 51 from impact 785:790 arg1 binding 865:871 binding 865:871 binding in APCs 865:879 The vaccine constructs were designed with an alanine spacer between the O-linked mannose moieties to investigate the impact of distance between the mannose units on receptor-mediated uptake and/or binding in APCs. 26735314 4 51 from impact 785:790 arg1 uptake 851:856 receptor-mediated uptake 833:856 receptor-mediated uptake 833:856 The vaccine constructs were designed with an alanine spacer between the O-linked mannose moieties to investigate the impact of distance between the mannose units on receptor-mediated uptake and/or binding in APCs. 26735314 3 52 theme constructs 411:420 arg1 library 392:398 a library 390:398 a library of vaccine constructs comprising fluorescently labeled mannosylated lipid-dendrimers that contained the ovalbumin CD4(+) epitope, OVA(323-339), as the model peptide antigen 390:571 In the present study, a library of vaccine constructs comprising fluorescently labeled mannosylated lipid-dendrimers that contained the ovalbumin CD4(+) epitope, OVA(323-339), as the model peptide antigen were synthesized using fluorenylmethyloxycarbonyl (Fmoc) solid phase peptide synthesis (SPPS). 26735314 1 53 from receptor 201:208 arg1 recognition 222:232 pathogen recognition 213:232 pathogen recognition 213:232 Present on the surface of antigen presenting cells (APCs), the mannose receptor (MR) has long been recognized as a front-line receptor in pathogen recognition. 26735314 7 54 theme mannose 1539:1545 arg1 moieties 1557:1564 both mannose and lipid moieties 1534:1564 moieties 1557:1564 To address the specificity of receptor uptake, surface plasmon resonance studies were performed using biacore technology and confirmed high affinity of the mannosylated and lipidated vaccine constructs toward the MR. These studies confirm that both mannose and lipid moieties play significant roles in receptor-mediated uptake on APCs, potentially facilitating vaccine development. 26735314 1 55 theme cells 120:124 arg1 surface 90:96 the surface 86:96 the surface of antigen presenting cells (APCs) 86:131 Present on the surface of antigen presenting cells (APCs), the mannose receptor (MR) has long been recognized as a front-line receptor in pathogen recognition. 26735314 0 56 theme Targeting 53:61 arg1 Properties 63:72 Receptor Targeting Properties 44:72 Receptor Targeting Properties 44:72 Synthesis of Mannosylated Lipopeptides with Receptor Targeting Properties. 26735314 3 57 theme solid 630:634 arg1 SPPS 661:664 SPPS 661:664 SPPS 661:664 In the present study, a library of vaccine constructs comprising fluorescently labeled mannosylated lipid-dendrimers that contained the ovalbumin CD4(+) epitope, OVA(323-339), as the model peptide antigen were synthesized using fluorenylmethyloxycarbonyl (Fmoc) solid phase peptide synthesis (SPPS). 26735314 3 57 theme solid 630:634 arg1 synthesis 650:658 fluorenylmethyloxycarbonyl (Fmoc) solid phase peptide synthesis 596:658 fluorenylmethyloxycarbonyl (Fmoc) solid phase peptide synthesis (SPPS) 596:665 In the present study, a library of vaccine constructs comprising fluorescently labeled mannosylated lipid-dendrimers that contained the ovalbumin CD4(+) epitope, OVA(323-339), as the model peptide antigen were synthesized using fluorenylmethyloxycarbonyl (Fmoc) solid phase peptide synthesis (SPPS). 26735314 4 58 from binding 865:871 arg1 APCs 876:879 APCs 876:879 APCs 876:879 The vaccine constructs were designed with an alanine spacer between the O-linked mannose moieties to investigate the impact of distance between the mannose units on receptor-mediated uptake and/or binding in APCs. 26735314 5 59 with peptide 1122:1128 arg1 mannose 1138:1144 no mannose 1135:1144 no mannose 1135:1144 Uptake studies performed on F4/80(+) and CD11c(+) cells showed significant uptake and/or binding for lipopeptides containing mannose, and also the lipopeptide without mannose when compared to the control peptides (peptide with no lipid and peptide with no mannose and no lipid). 26735314 4 60 theme vaccine 672:678 arg1 constructs 680:689 The vaccine constructs 668:689 The vaccine constructs 668:689 The vaccine constructs were designed with an alanine spacer between the O-linked mannose moieties to investigate the impact of distance between the mannose units on receptor-mediated uptake and/or binding in APCs. 26735314 4 61 theme mannose 749:755 arg1 moieties 757:764 the O-linked mannose moieties 736:764 the O-linked mannose moieties 736:764 The vaccine constructs were designed with an alanine spacer between the O-linked mannose moieties to investigate the impact of distance between the mannose units on receptor-mediated uptake and/or binding in APCs. 26735314 3 62 theme phase 636:640 arg1 SPPS 661:664 SPPS 661:664 SPPS 661:664 In the present study, a library of vaccine constructs comprising fluorescently labeled mannosylated lipid-dendrimers that contained the ovalbumin CD4(+) epitope, OVA(323-339), as the model peptide antigen were synthesized using fluorenylmethyloxycarbonyl (Fmoc) solid phase peptide synthesis (SPPS). 26735314 3 62 theme phase 636:640 arg1 synthesis 650:658 fluorenylmethyloxycarbonyl (Fmoc) solid phase peptide synthesis 596:658 fluorenylmethyloxycarbonyl (Fmoc) solid phase peptide synthesis (SPPS) 596:665 In the present study, a library of vaccine constructs comprising fluorescently labeled mannosylated lipid-dendrimers that contained the ovalbumin CD4(+) epitope, OVA(323-339), as the model peptide antigen were synthesized using fluorenylmethyloxycarbonyl (Fmoc) solid phase peptide synthesis (SPPS). 26735314 4 63 theme O-linked 740:747 arg1 moieties 757:764 the O-linked mannose moieties 736:764 the O-linked mannose moieties 736:764 The vaccine constructs were designed with an alanine spacer between the O-linked mannose moieties to investigate the impact of distance between the mannose units on receptor-mediated uptake and/or binding in APCs. 26735314 0 64 with Synthesis 0:8 arg1 Properties 63:72 Receptor Targeting Properties 44:72 Receptor Targeting Properties 44:72 Synthesis of Mannosylated Lipopeptides with Receptor Targeting Properties. 26735314 3 65 theme labeled 447:453 arg1 lipid-dendrimers 468:483 fluorescently labeled mannosylated lipid-dendrimers 433:483 fluorescently labeled mannosylated lipid-dendrimers that contained the ovalbumin CD4(+) epitope, OVA(323-339), as the model peptide antigen 433:571 In the present study, a library of vaccine constructs comprising fluorescently labeled mannosylated lipid-dendrimers that contained the ovalbumin CD4(+) epitope, OVA(323-339), as the model peptide antigen were synthesized using fluorenylmethyloxycarbonyl (Fmoc) solid phase peptide synthesis (SPPS). 26735314 1 66 theme antigen 101:107 arg1 APCs 127:130 APCs 127:130 APCs 127:130 Present on the surface of antigen presenting cells (APCs), the mannose receptor (MR) has long been recognized as a front-line receptor in pathogen recognition. 26735314 1 66 theme antigen 101:107 arg1 cells 120:124 antigen presenting cells 101:124 antigen presenting cells (APCs) 101:131 Present on the surface of antigen presenting cells (APCs), the mannose receptor (MR) has long been recognized as a front-line receptor in pathogen recognition. 26735314 7 67 theme resonance 1353:1361 arg1 studies 1363:1369 surface plasmon resonance studies 1337:1369 surface plasmon resonance studies 1337:1369 To address the specificity of receptor uptake, surface plasmon resonance studies were performed using biacore technology and confirmed high affinity of the mannosylated and lipidated vaccine constructs toward the MR. These studies confirm that both mannose and lipid moieties play significant roles in receptor-mediated uptake on APCs, potentially facilitating vaccine development. 26735314 3 68 theme Fmoc 624:627 arg1 SPPS 661:664 SPPS 661:664 SPPS 661:664 In the present study, a library of vaccine constructs comprising fluorescently labeled mannosylated lipid-dendrimers that contained the ovalbumin CD4(+) epitope, OVA(323-339), as the model peptide antigen were synthesized using fluorenylmethyloxycarbonyl (Fmoc) solid phase peptide synthesis (SPPS). 26735314 3 68 theme Fmoc 624:627 arg1 synthesis 650:658 fluorenylmethyloxycarbonyl (Fmoc) solid phase peptide synthesis 596:658 fluorenylmethyloxycarbonyl (Fmoc) solid phase peptide synthesis (SPPS) 596:665 In the present study, a library of vaccine constructs comprising fluorescently labeled mannosylated lipid-dendrimers that contained the ovalbumin CD4(+) epitope, OVA(323-339), as the model peptide antigen were synthesized using fluorenylmethyloxycarbonyl (Fmoc) solid phase peptide synthesis (SPPS). 26735314 5 69 with lipid 1153:1157 arg1 mannose 1138:1144 no mannose 1135:1144 no mannose 1135:1144 Uptake studies performed on F4/80(+) and CD11c(+) cells showed significant uptake and/or binding for lipopeptides containing mannose, and also the lipopeptide without mannose when compared to the control peptides (peptide with no lipid and peptide with no mannose and no lipid). 26735314 3 70 theme mannosylated 455:466 arg1 lipid-dendrimers 468:483 fluorescently labeled mannosylated lipid-dendrimers 433:483 fluorescently labeled mannosylated lipid-dendrimers that contained the ovalbumin CD4(+) epitope, OVA(323-339), as the model peptide antigen 433:571 In the present study, a library of vaccine constructs comprising fluorescently labeled mannosylated lipid-dendrimers that contained the ovalbumin CD4(+) epitope, OVA(323-339), as the model peptide antigen were synthesized using fluorenylmethyloxycarbonyl (Fmoc) solid phase peptide synthesis (SPPS). 26735314 1 71 theme front-line 190:199 arg1 receptor 201:208 a front-line receptor 188:208 a front-line receptor in pathogen recognition 188:232 Present on the surface of antigen presenting cells (APCs), the mannose receptor (MR) has long been recognized as a front-line receptor in pathogen recognition. 26735314 1 71 theme front-line 190:199 arg1 receptor 146:153 the mannose receptor 134:153 the mannose receptor (MR) 134:158 Present on the surface of antigen presenting cells (APCs), the mannose receptor (MR) has long been recognized as a front-line receptor in pathogen recognition. 26735314 3 72 theme model 551:555 arg1 OVA 530:532 OVA 530:532 OVA 530:532 In the present study, a library of vaccine constructs comprising fluorescently labeled mannosylated lipid-dendrimers that contained the ovalbumin CD4(+) epitope, OVA(323-339), as the model peptide antigen were synthesized using fluorenylmethyloxycarbonyl (Fmoc) solid phase peptide synthesis (SPPS). 26735314 3 72 theme model 551:555 arg1 epitope 521:527 epitope 521:527 epitope 521:527 In the present study, a library of vaccine constructs comprising fluorescently labeled mannosylated lipid-dendrimers that contained the ovalbumin CD4(+) epitope, OVA(323-339), as the model peptide antigen were synthesized using fluorenylmethyloxycarbonyl (Fmoc) solid phase peptide synthesis (SPPS). 26735314 3 72 theme model 551:555 arg1 antigen 565:571 the model peptide antigen 547:571 the model peptide antigen 547:571 In the present study, a library of vaccine constructs comprising fluorescently labeled mannosylated lipid-dendrimers that contained the ovalbumin CD4(+) epitope, OVA(323-339), as the model peptide antigen were synthesized using fluorenylmethyloxycarbonyl (Fmoc) solid phase peptide synthesis (SPPS). 26735314 3 72 theme model 551:555 arg1 CD4 514:516 the ovalbumin CD4 500:516 the ovalbumin CD4 500:516 In the present study, a library of vaccine constructs comprising fluorescently labeled mannosylated lipid-dendrimers that contained the ovalbumin CD4(+) epitope, OVA(323-339), as the model peptide antigen were synthesized using fluorenylmethyloxycarbonyl (Fmoc) solid phase peptide synthesis (SPPS). 26735314 3 73 theme ovalbumin 504:512 arg1 OVA 530:532 OVA 530:532 OVA 530:532 In the present study, a library of vaccine constructs comprising fluorescently labeled mannosylated lipid-dendrimers that contained the ovalbumin CD4(+) epitope, OVA(323-339), as the model peptide antigen were synthesized using fluorenylmethyloxycarbonyl (Fmoc) solid phase peptide synthesis (SPPS). 26735314 3 73 theme ovalbumin 504:512 arg1 epitope 521:527 epitope 521:527 epitope 521:527 In the present study, a library of vaccine constructs comprising fluorescently labeled mannosylated lipid-dendrimers that contained the ovalbumin CD4(+) epitope, OVA(323-339), as the model peptide antigen were synthesized using fluorenylmethyloxycarbonyl (Fmoc) solid phase peptide synthesis (SPPS). 26735314 3 73 theme ovalbumin 504:512 arg1 323-339 534:540 323-339 534:540 323-339 534:540 In the present study, a library of vaccine constructs comprising fluorescently labeled mannosylated lipid-dendrimers that contained the ovalbumin CD4(+) epitope, OVA(323-339), as the model peptide antigen were synthesized using fluorenylmethyloxycarbonyl (Fmoc) solid phase peptide synthesis (SPPS). 26735314 3 73 theme ovalbumin 504:512 arg1 antigen 565:571 the model peptide antigen 547:571 the model peptide antigen 547:571 In the present study, a library of vaccine constructs comprising fluorescently labeled mannosylated lipid-dendrimers that contained the ovalbumin CD4(+) epitope, OVA(323-339), as the model peptide antigen were synthesized using fluorenylmethyloxycarbonyl (Fmoc) solid phase peptide synthesis (SPPS). 26735314 3 73 theme ovalbumin 504:512 arg1 CD4 514:516 the ovalbumin CD4 500:516 the ovalbumin CD4 500:516 In the present study, a library of vaccine constructs comprising fluorescently labeled mannosylated lipid-dendrimers that contained the ovalbumin CD4(+) epitope, OVA(323-339), as the model peptide antigen were synthesized using fluorenylmethyloxycarbonyl (Fmoc) solid phase peptide synthesis (SPPS). 26735314 7 74 gly mannosylated 1446:1457 arg1 constructs 1481:1490 the mannosylated and lipidated vaccine constructs 1442:1490 the mannosylated and lipidated vaccine constructs 1442:1490 To address the specificity of receptor uptake, surface plasmon resonance studies were performed using biacore technology and confirmed high affinity of the mannosylated and lipidated vaccine constructs toward the MR. These studies confirm that both mannose and lipid moieties play significant roles in receptor-mediated uptake on APCs, potentially facilitating vaccine development. 26735314 7 75 theme high 1425:1428 arg1 affinity 1430:1437 high affinity 1425:1437 high affinity of the mannosylated and lipidated vaccine constructs toward the MR. These studies confirm that both mannose and lipid moieties play significant roles in receptor-mediated uptake on APCs, potentially facilitating vaccine development 1425:1669 To address the specificity of receptor uptake, surface plasmon resonance studies were performed using biacore technology and confirmed high affinity of the mannosylated and lipidated vaccine constructs toward the MR. These studies confirm that both mannose and lipid moieties play significant roles in receptor-mediated uptake on APCs, potentially facilitating vaccine development. 26735314 3 76 theme peptide 557:563 arg1 OVA 530:532 OVA 530:532 OVA 530:532 In the present study, a library of vaccine constructs comprising fluorescently labeled mannosylated lipid-dendrimers that contained the ovalbumin CD4(+) epitope, OVA(323-339), as the model peptide antigen were synthesized using fluorenylmethyloxycarbonyl (Fmoc) solid phase peptide synthesis (SPPS). 26735314 3 76 theme peptide 557:563 arg1 epitope 521:527 epitope 521:527 epitope 521:527 In the present study, a library of vaccine constructs comprising fluorescently labeled mannosylated lipid-dendrimers that contained the ovalbumin CD4(+) epitope, OVA(323-339), as the model peptide antigen were synthesized using fluorenylmethyloxycarbonyl (Fmoc) solid phase peptide synthesis (SPPS). 26735314 3 76 theme peptide 557:563 arg1 antigen 565:571 the model peptide antigen 547:571 the model peptide antigen 547:571 In the present study, a library of vaccine constructs comprising fluorescently labeled mannosylated lipid-dendrimers that contained the ovalbumin CD4(+) epitope, OVA(323-339), as the model peptide antigen were synthesized using fluorenylmethyloxycarbonyl (Fmoc) solid phase peptide synthesis (SPPS). 26735314 3 76 theme peptide 557:563 arg1 CD4 514:516 the ovalbumin CD4 500:516 the ovalbumin CD4 500:516 In the present study, a library of vaccine constructs comprising fluorescently labeled mannosylated lipid-dendrimers that contained the ovalbumin CD4(+) epitope, OVA(323-339), as the model peptide antigen were synthesized using fluorenylmethyloxycarbonyl (Fmoc) solid phase peptide synthesis (SPPS). 27157803 0 0 theme Articular 78:86 arg1 Cartilage 88:96 Articular Cartilage 78:96 Articular Cartilage 78:96 Galectin-3 Binds to Lubricin and Reinforces the Lubricating Boundary Layer of Articular Cartilage. 27157803 8 1 theme arthritis 1549:1557 arg1 progression 1534:1544 progression 1534:1544 progression 1534:1544 Together, our results suggest that galectin-3 reinforces the lubricin boundary layer; which, in turn, enhances cartilage lubrication and may delay the onset and progression of arthritis. 27157803 8 1 theme arthritis 1549:1557 arg1 onset 1524:1528 onset 1524:1528 onset 1524:1528 Together, our results suggest that galectin-3 reinforces the lubricin boundary layer; which, in turn, enhances cartilage lubrication and may delay the onset and progression of arthritis. 27157803 2 2 gly glycosylation 311:323 arg1 lubricating 390:400 its boundary lubricating function 377:409 its boundary lubricating function 377:409 Extensive O-linked glycosylation within lubricin's mucin-rich domain is critical for its boundary lubricating function; however, it is unknown exactly how glycosylation facilitates cartilage lubrication. 27157803 2 2 gly glycosylation 311:323 arg1 boundary 381:388 its boundary lubricating function 377:409 its boundary lubricating function 377:409 Extensive O-linked glycosylation within lubricin's mucin-rich domain is critical for its boundary lubricating function; however, it is unknown exactly how glycosylation facilitates cartilage lubrication. 27157803 3 3 theme lubricin 519:526 arg1 glycome 528:534 the lubricin glycome 515:534 the lubricin glycome 515:534 Here, we find that the lubricin glycome is enriched with terminal β-galactosides, known binding partners for a family of multivalent lectins called galectins. 27157803 4 4 from fluid 706:710 arg1 present 686:692 present 686:692 present 686:692 Of the galectin family members present in synovial fluid, we find that galectin-3 is a specific, high-affinity binding partner for lubricin. 27157803 6 5 theme binding 1037:1043 arg1 inhibition 1014:1023 competitive inhibition 1002:1023 competitive inhibition of galectin binding 1002:1043 We find that competitive inhibition of galectin binding results in lubricin loss from the cartilage surface, and addition of multimeric galectin-3 enhances cartilage lubrication. 27157803 7 6 theme osteoarthritic 1239:1252 arg1 cartilage 1254:1262 osteoarthritic cartilage 1239:1262 osteoarthritic cartilage 1239:1262 We also find that galectin-3 has low affinity for the surface layer of osteoarthritic cartilage and has reduced affinity for sialylated O-glycans, a glycophenotype associated with inflammatory conditions. 27157803 2 7 theme Extensive 292:300 arg1 glycosylation 311:323 Extensive O-linked glycosylation 292:323 Extensive O-linked glycosylation within lubricin's mucin-rich domain 292:359 Extensive O-linked glycosylation within lubricin's mucin-rich domain is critical for its boundary lubricating function; however, it is unknown exactly how glycosylation facilitates cartilage lubrication. 27157803 3 8 theme known 578:582 arg1 β-galactosides 562:575 terminal β-galactosides 553:575 terminal β-galactosides 553:575 Here, we find that the lubricin glycome is enriched with terminal β-galactosides, known binding partners for a family of multivalent lectins called galectins. 27157803 3 8 theme known 578:582 arg1 partners 592:599 known binding partners 578:599 known binding partners for a family of multivalent lectins called galectins 578:652 Here, we find that the lubricin glycome is enriched with terminal β-galactosides, known binding partners for a family of multivalent lectins called galectins. 27157803 1 9 theme lubricating 256:266 arg1 properties 268:277 its lubricating properties 252:277 its lubricating properties in solution 252:289 Lubricin is a mucinous, synovial fluid glycoprotein that enables near frictionless joint motion via adsorption to the surface of articular cartilage and its lubricating properties in solution. 27157803 0 10 theme Cartilage 88:96 arg1 Layer 69:73 the Lubricating Boundary Layer 44:73 the Lubricating Boundary Layer of Articular Cartilage 44:96 Galectin-3 Binds to Lubricin and Reinforces the Lubricating Boundary Layer of Articular Cartilage. 27157803 7 11 theme sialylated 1293:1302 arg1 O-glycans 1304:1312 sialylated O-glycans 1293:1312 sialylated O-glycans 1293:1312 We also find that galectin-3 has low affinity for the surface layer of osteoarthritic cartilage and has reduced affinity for sialylated O-glycans, a glycophenotype associated with inflammatory conditions. 27157803 7 11 theme sialylated 1293:1302 arg1 glycophenotype 1317:1330 a glycophenotype 1315:1330 a glycophenotype associated with inflammatory conditions 1315:1370 We also find that galectin-3 has low affinity for the surface layer of osteoarthritic cartilage and has reduced affinity for sialylated O-glycans, a glycophenotype associated with inflammatory conditions. 27157803 4 12 theme binding 766:772 arg1 partner 774:780 a specific, high-affinity binding partner 740:780 a specific, high-affinity binding partner for lubricin 740:793 Of the galectin family members present in synovial fluid, we find that galectin-3 is a specific, high-affinity binding partner for lubricin. 27157803 4 12 theme binding 766:772 arg1 galectin-3 726:735 galectin-3 726:735 galectin-3 726:735 Of the galectin family members present in synovial fluid, we find that galectin-3 is a specific, high-affinity binding partner for lubricin. 27157803 5 13 theme lubricin 964:971 arg1 layer 982:986 the lubricin boundary layer 960:986 the lubricin boundary layer 960:986 Considering the known ability of galectin-3 to crosslink glycoproteins, we hypothesized that galectins could augment lubrication via biomechanical stabilization of the lubricin boundary layer. 27157803 5 14 gly glycoproteins 853:865 arg1 glycoproteins 853:865 glycoproteins 853:865 glycoproteins 853:865 Considering the known ability of galectin-3 to crosslink glycoproteins, we hypothesized that galectins could augment lubrication via biomechanical stabilization of the lubricin boundary layer. 27157803 4 15 theme specific 742:749 arg1 partner 774:780 a specific, high-affinity binding partner 740:780 a specific, high-affinity binding partner for lubricin 740:793 Of the galectin family members present in synovial fluid, we find that galectin-3 is a specific, high-affinity binding partner for lubricin. 27157803 4 15 theme specific 742:749 arg1 galectin-3 726:735 galectin-3 726:735 galectin-3 726:735 Of the galectin family members present in synovial fluid, we find that galectin-3 is a specific, high-affinity binding partner for lubricin. 27157803 7 16 contain has 1197:1199 arg1 galectin-3 1186:1195 galectin-3 1186:1195 galectin-3 1186:1195 We also find that galectin-3 has low affinity for the surface layer of osteoarthritic cartilage and has reduced affinity for sialylated O-glycans, a glycophenotype associated with inflammatory conditions. 27157803 7 16 contain has 1197:1199 arg2 affinity 1205:1212 low affinity 1201:1212 low affinity for the surface layer of osteoarthritic cartilage 1201:1262 We also find that galectin-3 has low affinity for the surface layer of osteoarthritic cartilage and has reduced affinity for sialylated O-glycans, a glycophenotype associated with inflammatory conditions. 27157803 4 17 from present 686:692 arg1 fluid 706:710 synovial fluid 697:710 synovial fluid 697:710 Of the galectin family members present in synovial fluid, we find that galectin-3 is a specific, high-affinity binding partner for lubricin. 27157803 1 18 theme near 164:167 arg1 motion 188:193 near frictionless joint motion 164:193 near frictionless joint motion 164:193 Lubricin is a mucinous, synovial fluid glycoprotein that enables near frictionless joint motion via adsorption to the surface of articular cartilage and its lubricating properties in solution. 27157803 5 19 theme known 812:816 arg1 ability 818:824 the known ability 808:824 the known ability of galectin-3 to crosslink glycoproteins 808:865 Considering the known ability of galectin-3 to crosslink glycoproteins, we hypothesized that galectins could augment lubrication via biomechanical stabilization of the lubricin boundary layer. 27157803 5 20 theme biomechanical 929:941 arg1 stabilization 943:955 biomechanical stabilization 929:955 biomechanical stabilization of the lubricin boundary layer 929:986 Considering the known ability of galectin-3 to crosslink glycoproteins, we hypothesized that galectins could augment lubrication via biomechanical stabilization of the lubricin boundary layer. 27157803 5 21 theme boundary 973:980 arg1 layer 982:986 the lubricin boundary layer 960:986 the lubricin boundary layer 960:986 Considering the known ability of galectin-3 to crosslink glycoproteins, we hypothesized that galectins could augment lubrication via biomechanical stabilization of the lubricin boundary layer. 27157803 6 22 theme galectin-3 1125:1134 arg1 addition 1102:1109 addition 1102:1109 addition of multimeric galectin-3 1102:1134 We find that competitive inhibition of galectin binding results in lubricin loss from the cartilage surface, and addition of multimeric galectin-3 enhances cartilage lubrication. 27157803 1 23 theme frictionless 169:180 arg1 motion 188:193 near frictionless joint motion 164:193 near frictionless joint motion 164:193 Lubricin is a mucinous, synovial fluid glycoprotein that enables near frictionless joint motion via adsorption to the surface of articular cartilage and its lubricating properties in solution. 27157803 7 24 theme inflammatory 1348:1359 arg1 conditions 1361:1370 inflammatory conditions 1348:1370 inflammatory conditions 1348:1370 We also find that galectin-3 has low affinity for the surface layer of osteoarthritic cartilage and has reduced affinity for sialylated O-glycans, a glycophenotype associated with inflammatory conditions. 27157803 3 25 theme binding 584:590 arg1 β-galactosides 562:575 terminal β-galactosides 553:575 terminal β-galactosides 553:575 Here, we find that the lubricin glycome is enriched with terminal β-galactosides, known binding partners for a family of multivalent lectins called galectins. 27157803 3 25 theme binding 584:590 arg1 partners 592:599 known binding partners 578:599 known binding partners for a family of multivalent lectins called galectins 578:652 Here, we find that the lubricin glycome is enriched with terminal β-galactosides, known binding partners for a family of multivalent lectins called galectins. 27157803 1 26 theme joint 182:186 arg1 motion 188:193 near frictionless joint motion 164:193 near frictionless joint motion 164:193 Lubricin is a mucinous, synovial fluid glycoprotein that enables near frictionless joint motion via adsorption to the surface of articular cartilage and its lubricating properties in solution. 27157803 7 27 theme surface 1222:1228 arg1 layer 1230:1234 the surface layer 1218:1234 the surface layer of osteoarthritic cartilage 1218:1262 We also find that galectin-3 has low affinity for the surface layer of osteoarthritic cartilage and has reduced affinity for sialylated O-glycans, a glycophenotype associated with inflammatory conditions. 27157803 5 28 theme layer 982:986 arg1 stabilization 943:955 biomechanical stabilization 929:955 biomechanical stabilization of the lubricin boundary layer 929:986 Considering the known ability of galectin-3 to crosslink glycoproteins, we hypothesized that galectins could augment lubrication via biomechanical stabilization of the lubricin boundary layer. 27157803 2 29 theme lubricating 390:400 arg1 function 402:409 its boundary lubricating function 377:409 its boundary lubricating function 377:409 Extensive O-linked glycosylation within lubricin's mucin-rich domain is critical for its boundary lubricating function; however, it is unknown exactly how glycosylation facilitates cartilage lubrication. 27157803 5 30 theme galectin-3 829:838 arg1 ability 818:824 the known ability 808:824 the known ability of galectin-3 to crosslink glycoproteins 808:865 Considering the known ability of galectin-3 to crosslink glycoproteins, we hypothesized that galectins could augment lubrication via biomechanical stabilization of the lubricin boundary layer. 27157803 6 31 theme competitive 1002:1012 arg1 inhibition 1014:1023 competitive inhibition 1002:1023 competitive inhibition of galectin binding 1002:1043 We find that competitive inhibition of galectin binding results in lubricin loss from the cartilage surface, and addition of multimeric galectin-3 enhances cartilage lubrication. 27157803 6 32 from surface 1089:1095 arg1 loss 1065:1068 lubricin loss 1056:1068 lubricin loss from the cartilage surface 1056:1095 We find that competitive inhibition of galectin binding results in lubricin loss from the cartilage surface, and addition of multimeric galectin-3 enhances cartilage lubrication. 27157803 8 33 theme boundary 1443:1450 arg1 layer 1452:1456 the lubricin boundary layer; 1430:1457 the lubricin boundary layer; which, in turn, enhances cartilage lubrication and may delay the onset and progression of arthritis 1430:1557 Together, our results suggest that galectin-3 reinforces the lubricin boundary layer; which, in turn, enhances cartilage lubrication and may delay the onset and progression of arthritis. 27157803 1 34 from properties 268:277 arg1 solution 282:289 solution 282:289 solution 282:289 Lubricin is a mucinous, synovial fluid glycoprotein that enables near frictionless joint motion via adsorption to the surface of articular cartilage and its lubricating properties in solution. 27157803 2 35 theme O-linked 302:309 arg1 glycosylation 311:323 Extensive O-linked glycosylation 292:323 Extensive O-linked glycosylation within lubricin's mucin-rich domain 292:359 Extensive O-linked glycosylation within lubricin's mucin-rich domain is critical for its boundary lubricating function; however, it is unknown exactly how glycosylation facilitates cartilage lubrication. 27157803 2 36 theme boundary 381:388 arg1 function 402:409 its boundary lubricating function 377:409 its boundary lubricating function 377:409 Extensive O-linked glycosylation within lubricin's mucin-rich domain is critical for its boundary lubricating function; however, it is unknown exactly how glycosylation facilitates cartilage lubrication. 27157803 8 37 dep onset 1524:1528 arg1 the 1520:1522 the 1520:1522 the 1520:1522 Together, our results suggest that galectin-3 reinforces the lubricin boundary layer; which, in turn, enhances cartilage lubrication and may delay the onset and progression of arthritis. 27157803 7 38 gly sialylated 1293:1302 arg1 O-glycans 1304:1312 sialylated O-glycans 1293:1312 sialylated O-glycans 1293:1312 We also find that galectin-3 has low affinity for the surface layer of osteoarthritic cartilage and has reduced affinity for sialylated O-glycans, a glycophenotype associated with inflammatory conditions. 27157803 7 38 gly sialylated 1293:1302 arg1 glycophenotype 1317:1330 a glycophenotype 1315:1330 a glycophenotype associated with inflammatory conditions 1315:1370 We also find that galectin-3 has low affinity for the surface layer of osteoarthritic cartilage and has reduced affinity for sialylated O-glycans, a glycophenotype associated with inflammatory conditions. 27157803 6 39 theme cartilage 1079:1087 arg1 surface 1089:1095 the cartilage surface 1075:1095 the cartilage surface 1075:1095 We find that competitive inhibition of galectin binding results in lubricin loss from the cartilage surface, and addition of multimeric galectin-3 enhances cartilage lubrication. 27157803 4 40 theme present 686:692 arg1 members 678:684 the galectin family members 658:684 the galectin family members present in synovial fluid 658:710 Of the galectin family members present in synovial fluid, we find that galectin-3 is a specific, high-affinity binding partner for lubricin. 27157803 4 41 theme galectin 662:669 arg1 members 678:684 the galectin family members 658:684 the galectin family members present in synovial fluid 658:710 Of the galectin family members present in synovial fluid, we find that galectin-3 is a specific, high-affinity binding partner for lubricin. 27157803 6 42 theme multimeric 1114:1123 arg1 galectin-3 1125:1134 multimeric galectin-3 1114:1134 multimeric galectin-3 1114:1134 We find that competitive inhibition of galectin binding results in lubricin loss from the cartilage surface, and addition of multimeric galectin-3 enhances cartilage lubrication. 27157803 7 43 theme low 1201:1203 arg1 affinity 1205:1212 low affinity 1201:1212 low affinity for the surface layer of osteoarthritic cartilage 1201:1262 We also find that galectin-3 has low affinity for the surface layer of osteoarthritic cartilage and has reduced affinity for sialylated O-glycans, a glycophenotype associated with inflammatory conditions. 27157803 4 44 attach present 686:692 arg2 members 678:684 the galectin family members 658:684 the galectin family members present in synovial fluid 658:710 Of the galectin family members present in synovial fluid, we find that galectin-3 is a specific, high-affinity binding partner for lubricin. 27157803 4 44 attach present 686:692 arg1 fluid 706:710 synovial fluid 697:710 synovial fluid 697:710 Of the galectin family members present in synovial fluid, we find that galectin-3 is a specific, high-affinity binding partner for lubricin. 27157803 6 45 theme lubricin 1056:1063 arg1 loss 1065:1068 lubricin loss 1056:1068 lubricin loss from the cartilage surface 1056:1095 We find that competitive inhibition of galectin binding results in lubricin loss from the cartilage surface, and addition of multimeric galectin-3 enhances cartilage lubrication. 27157803 0 46 theme Lubricating 48:58 arg1 Layer 69:73 the Lubricating Boundary Layer 44:73 the Lubricating Boundary Layer of Articular Cartilage 44:96 Galectin-3 Binds to Lubricin and Reinforces the Lubricating Boundary Layer of Articular Cartilage. 27157803 2 47 link O-linked 302:309 arg1 glycosylation 311:323 Extensive O-linked glycosylation 292:323 Extensive O-linked glycosylation within lubricin's mucin-rich domain 292:359 Extensive O-linked glycosylation within lubricin's mucin-rich domain is critical for its boundary lubricating function; however, it is unknown exactly how glycosylation facilitates cartilage lubrication. 27157803 1 48 gly glycoprotein 138:149 arg1 glycoprotein 138:149 a mucinous, synovial fluid glycoprotein 111:149 glycoprotein 138:149 Lubricin is a mucinous, synovial fluid glycoprotein that enables near frictionless joint motion via adsorption to the surface of articular cartilage and its lubricating properties in solution. 27157803 1 48 gly glycoprotein 138:149 arg1 Lubricin 99:106 Lubricin 99:106 Lubricin 99:106 Lubricin is a mucinous, synovial fluid glycoprotein that enables near frictionless joint motion via adsorption to the surface of articular cartilage and its lubricating properties in solution. 27157803 8 49 theme lubricin 1434:1441 arg1 layer 1452:1456 the lubricin boundary layer; 1430:1457 the lubricin boundary layer; which, in turn, enhances cartilage lubrication and may delay the onset and progression of arthritis 1430:1557 Together, our results suggest that galectin-3 reinforces the lubricin boundary layer; which, in turn, enhances cartilage lubrication and may delay the onset and progression of arthritis. 27157803 2 50 theme cartilage 473:481 arg1 lubrication 483:493 cartilage lubrication 473:493 cartilage lubrication 473:493 Extensive O-linked glycosylation within lubricin's mucin-rich domain is critical for its boundary lubricating function; however, it is unknown exactly how glycosylation facilitates cartilage lubrication. 27157803 7 51 theme cartilage 1254:1262 arg1 layer 1230:1234 the surface layer 1218:1234 the surface layer of osteoarthritic cartilage 1218:1262 We also find that galectin-3 has low affinity for the surface layer of osteoarthritic cartilage and has reduced affinity for sialylated O-glycans, a glycophenotype associated with inflammatory conditions. 27157803 1 52 theme mucinous 113:120 arg1 glycoprotein 138:149 a mucinous, synovial fluid glycoprotein 111:149 glycoprotein 138:149 Lubricin is a mucinous, synovial fluid glycoprotein that enables near frictionless joint motion via adsorption to the surface of articular cartilage and its lubricating properties in solution. 27157803 1 52 theme mucinous 113:120 arg1 Lubricin 99:106 Lubricin 99:106 Lubricin 99:106 Lubricin is a mucinous, synovial fluid glycoprotein that enables near frictionless joint motion via adsorption to the surface of articular cartilage and its lubricating properties in solution. 27157803 8 53 theme cartilage 1484:1492 arg1 lubrication 1494:1504 cartilage lubrication 1484:1504 cartilage lubrication 1484:1504 Together, our results suggest that galectin-3 reinforces the lubricin boundary layer; which, in turn, enhances cartilage lubrication and may delay the onset and progression of arthritis. 27157803 1 54 from adsorption 199:208 arg1 solution 282:289 solution 282:289 solution 282:289 Lubricin is a mucinous, synovial fluid glycoprotein that enables near frictionless joint motion via adsorption to the surface of articular cartilage and its lubricating properties in solution. 27157803 2 55 theme mucin-rich 343:352 arg1 domain 354:359 lubricin's mucin-rich domain 332:359 lubricin's mucin-rich domain 332:359 Extensive O-linked glycosylation within lubricin's mucin-rich domain is critical for its boundary lubricating function; however, it is unknown exactly how glycosylation facilitates cartilage lubrication. 27157803 6 56 theme galectin 1028:1035 arg1 binding 1037:1043 galectin binding 1028:1043 galectin binding 1028:1043 We find that competitive inhibition of galectin binding results in lubricin loss from the cartilage surface, and addition of multimeric galectin-3 enhances cartilage lubrication. 27157803 3 57 theme terminal 553:560 arg1 β-galactosides 562:575 terminal β-galactosides 553:575 terminal β-galactosides 553:575 Here, we find that the lubricin glycome is enriched with terminal β-galactosides, known binding partners for a family of multivalent lectins called galectins. 27157803 3 57 theme terminal 553:560 arg1 partners 592:599 known binding partners 578:599 known binding partners for a family of multivalent lectins called galectins 578:652 Here, we find that the lubricin glycome is enriched with terminal β-galactosides, known binding partners for a family of multivalent lectins called galectins. 27157803 7 58 contain has 1268:1270 arg2 affinity 1280:1287 reduced affinity 1272:1287 reduced affinity for sialylated O-glycans, a glycophenotype associated with inflammatory conditions 1272:1370 We also find that galectin-3 has low affinity for the surface layer of osteoarthritic cartilage and has reduced affinity for sialylated O-glycans, a glycophenotype associated with inflammatory conditions. 27157803 7 58 contain has 1268:1270 arg1 galectin-3 1186:1195 galectin-3 1186:1195 galectin-3 1186:1195 We also find that galectin-3 has low affinity for the surface layer of osteoarthritic cartilage and has reduced affinity for sialylated O-glycans, a glycophenotype associated with inflammatory conditions. 27157803 1 59 theme synovial 123:130 arg1 glycoprotein 138:149 a mucinous, synovial fluid glycoprotein 111:149 glycoprotein 138:149 Lubricin is a mucinous, synovial fluid glycoprotein that enables near frictionless joint motion via adsorption to the surface of articular cartilage and its lubricating properties in solution. 27157803 1 59 theme synovial 123:130 arg1 Lubricin 99:106 Lubricin 99:106 Lubricin 99:106 Lubricin is a mucinous, synovial fluid glycoprotein that enables near frictionless joint motion via adsorption to the surface of articular cartilage and its lubricating properties in solution. 27157803 4 60 dep specific 742:749 arg1 high-affinity 752:764 high-affinity 752:764 high-affinity 752:764 Of the galectin family members present in synovial fluid, we find that galectin-3 is a specific, high-affinity binding partner for lubricin. 27157803 7 61 theme reduced 1272:1278 arg1 affinity 1280:1287 reduced affinity 1272:1287 reduced affinity for sialylated O-glycans, a glycophenotype associated with inflammatory conditions 1272:1370 We also find that galectin-3 has low affinity for the surface layer of osteoarthritic cartilage and has reduced affinity for sialylated O-glycans, a glycophenotype associated with inflammatory conditions. 27157803 6 62 theme cartilage 1145:1153 arg1 lubrication 1155:1165 cartilage lubrication 1145:1165 cartilage lubrication 1145:1165 We find that competitive inhibition of galectin binding results in lubricin loss from the cartilage surface, and addition of multimeric galectin-3 enhances cartilage lubrication. 27157803 3 63 theme multivalent 617:627 arg1 lectins 629:635 multivalent lectins 617:635 multivalent lectins called galectins 617:652 Here, we find that the lubricin glycome is enriched with terminal β-galactosides, known binding partners for a family of multivalent lectins called galectins. 27157803 1 64 theme fluid 132:136 arg1 glycoprotein 138:149 a mucinous, synovial fluid glycoprotein 111:149 glycoprotein 138:149 Lubricin is a mucinous, synovial fluid glycoprotein that enables near frictionless joint motion via adsorption to the surface of articular cartilage and its lubricating properties in solution. 27157803 1 64 theme fluid 132:136 arg1 Lubricin 99:106 Lubricin 99:106 Lubricin 99:106 Lubricin is a mucinous, synovial fluid glycoprotein that enables near frictionless joint motion via adsorption to the surface of articular cartilage and its lubricating properties in solution. 27157803 4 65 theme family 671:676 arg1 members 678:684 the galectin family members 658:684 the galectin family members present in synovial fluid 658:710 Of the galectin family members present in synovial fluid, we find that galectin-3 is a specific, high-affinity binding partner for lubricin. 27157803 1 66 theme articular 228:236 arg1 cartilage 238:246 articular cartilage 228:246 articular cartilage 228:246 Lubricin is a mucinous, synovial fluid glycoprotein that enables near frictionless joint motion via adsorption to the surface of articular cartilage and its lubricating properties in solution. 27157803 0 67 theme Boundary 60:67 arg1 Layer 69:73 the Lubricating Boundary Layer 44:73 the Lubricating Boundary Layer of Articular Cartilage 44:96 Galectin-3 Binds to Lubricin and Reinforces the Lubricating Boundary Layer of Articular Cartilage. 27157803 3 68 theme lectins 629:635 arg1 family 607:612 a family 605:612 a family of multivalent lectins called galectins 605:652 Here, we find that the lubricin glycome is enriched with terminal β-galactosides, known binding partners for a family of multivalent lectins called galectins. 27157803 4 69 theme synovial 697:704 arg1 fluid 706:710 synovial fluid 697:710 synovial fluid 697:710 Of the galectin family members present in synovial fluid, we find that galectin-3 is a specific, high-affinity binding partner for lubricin. 27157803 1 70 theme cartilage 238:246 arg1 surface 217:223 the surface 213:223 the surface of articular cartilage 213:246 Lubricin is a mucinous, synovial fluid glycoprotein that enables near frictionless joint motion via adsorption to the surface of articular cartilage and its lubricating properties in solution. 26572344 3 0 dep characterized 346:358 arg1 methylation 407:417 methylation 407:417 methylation with trideuterated iodomethane 407:448 A mannan with a main chain of α-(1 → 6)-linked-Manp units, branched at O-2 mainly by side-chains of 2-O-linked-α-Manp units was chemically sulfated, structurally characterized by NMR and GC-MS (methylation, desulfation and methylation with trideuterated iodomethane), and tested in vitro and in vivo on blood coagulation models. 26572344 3 0 dep characterized 346:358 arg1 desulfation 391:401 desulfation 391:401 desulfation 391:401 A mannan with a main chain of α-(1 → 6)-linked-Manp units, branched at O-2 mainly by side-chains of 2-O-linked-α-Manp units was chemically sulfated, structurally characterized by NMR and GC-MS (methylation, desulfation and methylation with trideuterated iodomethane), and tested in vitro and in vivo on blood coagulation models. 26572344 3 0 dep characterized 346:358 arg1 methylation 378:388 methylation 378:388 methylation 378:388 A mannan with a main chain of α-(1 → 6)-linked-Manp units, branched at O-2 mainly by side-chains of 2-O-linked-α-Manp units was chemically sulfated, structurally characterized by NMR and GC-MS (methylation, desulfation and methylation with trideuterated iodomethane), and tested in vitro and in vivo on blood coagulation models. 26572344 6 1 theme hemostatic 838:847 arg1 agents 849:854 hemostatic agents 838:854 hemostatic agents 838:854 Polymers such as the sulfated mannan could be a helpful source of hemostatic agents to prevent hemorrhagic states. 26572344 3 2 theme 2-O-linked-α-Manp 284:300 arg1 units 302:306 2-O-linked-α-Manp units 284:306 2-O-linked-α-Manp units 284:306 A mannan with a main chain of α-(1 → 6)-linked-Manp units, branched at O-2 mainly by side-chains of 2-O-linked-α-Manp units was chemically sulfated, structurally characterized by NMR and GC-MS (methylation, desulfation and methylation with trideuterated iodomethane), and tested in vitro and in vivo on blood coagulation models. 26572344 4 3 theme high 542:545 arg1 degree 547:552 a high degree 540:552 a high degree of substitution on the sulfated polysaccharide 540:599 Chemical analyses indicate a high degree of substitution on the sulfated polysaccharide. 26572344 6 4 theme hemorrhagic 867:877 arg1 states 879:884 hemorrhagic states 867:884 hemorrhagic states 867:884 Polymers such as the sulfated mannan could be a helpful source of hemostatic agents to prevent hemorrhagic states. 26572344 5 5 theme procoagulant 626:637 arg1 polymer 607:613 This polymer 602:613 This polymer 602:613 This polymer acted as a procoagulant agent, increasing blood coagulation in normal and hemophilic plasma, activated platelet aggregation and also decreased ex vivo aPTT. 26572344 5 5 theme procoagulant 626:637 arg1 agent 639:643 a procoagulant agent 624:643 a procoagulant agent 624:643 This polymer acted as a procoagulant agent, increasing blood coagulation in normal and hemophilic plasma, activated platelet aggregation and also decreased ex vivo aPTT. 26572344 1 6 theme hemostasis 56:65 arg1 Disorders 43:51 Disorders 43:51 Disorders of hemostasis 43:65 Disorders of hemostasis can produce innumerous problems. 26572344 4 7 theme substitution 557:568 arg1 degree 547:552 a high degree 540:552 a high degree of substitution on the sulfated polysaccharide 540:599 Chemical analyses indicate a high degree of substitution on the sulfated polysaccharide. 26572344 2 8 theme procoagulant 163:174 arg1 agents 176:181 procoagulant agents 163:181 procoagulant agents 163:181 Polysaccharides have been studied both as anticoagulant and as procoagulant agents. 26572344 2 8 theme procoagulant 163:174 arg1 Polysaccharides 100:114 Polysaccharides 100:114 Polysaccharides 100:114 Polysaccharides have been studied both as anticoagulant and as procoagulant agents. 26572344 3 9 theme α- 214:215 arg1 units 236:240 α-(1 → 6)-linked-Manp units 214:240 α-(1 → 6)-linked-Manp units 214:240 A mannan with a main chain of α-(1 → 6)-linked-Manp units, branched at O-2 mainly by side-chains of 2-O-linked-α-Manp units was chemically sulfated, structurally characterized by NMR and GC-MS (methylation, desulfation and methylation with trideuterated iodomethane), and tested in vitro and in vivo on blood coagulation models. 26572344 4 10 from degree 547:552 arg1 polysaccharide 586:599 the sulfated polysaccharide 573:599 the sulfated polysaccharide 573:599 Chemical analyses indicate a high degree of substitution on the sulfated polysaccharide. 26572344 3 11 theme blood 487:491 arg1 models 505:510 blood coagulation models 487:510 blood coagulation models 487:510 A mannan with a main chain of α-(1 → 6)-linked-Manp units, branched at O-2 mainly by side-chains of 2-O-linked-α-Manp units was chemically sulfated, structurally characterized by NMR and GC-MS (methylation, desulfation and methylation with trideuterated iodomethane), and tested in vitro and in vivo on blood coagulation models. 26572344 5 12 theme normal 678:683 arg1 plasma 700:705 normal and hemophilic plasma 678:705 normal and hemophilic plasma 678:705 This polymer acted as a procoagulant agent, increasing blood coagulation in normal and hemophilic plasma, activated platelet aggregation and also decreased ex vivo aPTT. 26572344 5 13 theme platelet 718:725 arg1 aggregation 727:737 platelet aggregation 718:737 platelet aggregation 718:737 This polymer acted as a procoagulant agent, increasing blood coagulation in normal and hemophilic plasma, activated platelet aggregation and also decreased ex vivo aPTT. 26572344 6 14 theme agents 849:854 arg1 source 828:833 a helpful source 818:833 a helpful source of hemostatic agents to prevent hemorrhagic states 818:884 Polymers such as the sulfated mannan could be a helpful source of hemostatic agents to prevent hemorrhagic states. 26572344 6 14 theme agents 849:854 arg1 mannan 802:807 the sulfated mannan 789:807 the sulfated mannan 789:807 Polymers such as the sulfated mannan could be a helpful source of hemostatic agents to prevent hemorrhagic states. 26572344 6 14 theme agents 849:854 arg1 Polymers 772:779 Polymers 772:779 Polymers such as the sulfated mannan 772:807 Polymers such as the sulfated mannan could be a helpful source of hemostatic agents to prevent hemorrhagic states. 26572344 3 15 theme -linked-Manp 223:234 arg1 units 236:240 α-(1 → 6)-linked-Manp units 214:240 α-(1 → 6)-linked-Manp units 214:240 A mannan with a main chain of α-(1 → 6)-linked-Manp units, branched at O-2 mainly by side-chains of 2-O-linked-α-Manp units was chemically sulfated, structurally characterized by NMR and GC-MS (methylation, desulfation and methylation with trideuterated iodomethane), and tested in vitro and in vivo on blood coagulation models. 26572344 3 16 theme main 200:203 arg1 chain 205:209 a main chain 198:209 a main chain of α-(1 → 6)-linked-Manp units, branched at O-2 mainly by side-chains of 2-O-linked-α-Manp units 198:306 A mannan with a main chain of α-(1 → 6)-linked-Manp units, branched at O-2 mainly by side-chains of 2-O-linked-α-Manp units was chemically sulfated, structurally characterized by NMR and GC-MS (methylation, desulfation and methylation with trideuterated iodomethane), and tested in vitro and in vivo on blood coagulation models. 26572344 3 17 theme coagulation 493:503 arg1 models 505:510 blood coagulation models 487:510 blood coagulation models 487:510 A mannan with a main chain of α-(1 → 6)-linked-Manp units, branched at O-2 mainly by side-chains of 2-O-linked-α-Manp units was chemically sulfated, structurally characterized by NMR and GC-MS (methylation, desulfation and methylation with trideuterated iodomethane), and tested in vitro and in vivo on blood coagulation models. 26572344 5 18 theme decreased 748:756 arg1 aPTT 766:769 decreased ex vivo aPTT 748:769 decreased ex vivo aPTT 748:769 This polymer acted as a procoagulant agent, increasing blood coagulation in normal and hemophilic plasma, activated platelet aggregation and also decreased ex vivo aPTT. 26572344 5 19 dep ex 758:759 arg1 vivo 761:764 vivo 761:764 vivo 761:764 This polymer acted as a procoagulant agent, increasing blood coagulation in normal and hemophilic plasma, activated platelet aggregation and also decreased ex vivo aPTT. 26572344 3 20 dep α- 214:215 arg1 → 219:219 1 → 6 217:221 1 → 6 217:221 A mannan with a main chain of α-(1 → 6)-linked-Manp units, branched at O-2 mainly by side-chains of 2-O-linked-α-Manp units was chemically sulfated, structurally characterized by NMR and GC-MS (methylation, desulfation and methylation with trideuterated iodomethane), and tested in vitro and in vivo on blood coagulation models. 26572344 4 21 theme Chemical 513:520 arg1 analyses 522:529 Chemical analyses 513:529 Chemical analyses 513:529 Chemical analyses indicate a high degree of substitution on the sulfated polysaccharide. 26572344 3 22 with methylation 378:388 arg1 iodomethane 438:448 trideuterated iodomethane 424:448 trideuterated iodomethane 424:448 A mannan with a main chain of α-(1 → 6)-linked-Manp units, branched at O-2 mainly by side-chains of 2-O-linked-α-Manp units was chemically sulfated, structurally characterized by NMR and GC-MS (methylation, desulfation and methylation with trideuterated iodomethane), and tested in vitro and in vivo on blood coagulation models. 26572344 5 23 theme ex 758:759 arg1 aPTT 766:769 decreased ex vivo aPTT 748:769 decreased ex vivo aPTT 748:769 This polymer acted as a procoagulant agent, increasing blood coagulation in normal and hemophilic plasma, activated platelet aggregation and also decreased ex vivo aPTT. 26572344 3 24 theme units 236:240 arg1 chain 205:209 a main chain 198:209 a main chain of α-(1 → 6)-linked-Manp units, branched at O-2 mainly by side-chains of 2-O-linked-α-Manp units 198:306 A mannan with a main chain of α-(1 → 6)-linked-Manp units, branched at O-2 mainly by side-chains of 2-O-linked-α-Manp units was chemically sulfated, structurally characterized by NMR and GC-MS (methylation, desulfation and methylation with trideuterated iodomethane), and tested in vitro and in vivo on blood coagulation models. 26572344 3 25 theme trideuterated 424:436 arg1 iodomethane 438:448 trideuterated iodomethane 424:448 trideuterated iodomethane 424:448 A mannan with a main chain of α-(1 → 6)-linked-Manp units, branched at O-2 mainly by side-chains of 2-O-linked-α-Manp units was chemically sulfated, structurally characterized by NMR and GC-MS (methylation, desulfation and methylation with trideuterated iodomethane), and tested in vitro and in vivo on blood coagulation models. 26572344 5 26 theme hemophilic 689:698 arg1 plasma 700:705 normal and hemophilic plasma 678:705 normal and hemophilic plasma 678:705 This polymer acted as a procoagulant agent, increasing blood coagulation in normal and hemophilic plasma, activated platelet aggregation and also decreased ex vivo aPTT. 26572344 6 27 theme helpful 820:826 arg1 source 828:833 a helpful source 818:833 a helpful source of hemostatic agents to prevent hemorrhagic states 818:884 Polymers such as the sulfated mannan could be a helpful source of hemostatic agents to prevent hemorrhagic states. 26572344 6 27 theme helpful 820:826 arg1 mannan 802:807 the sulfated mannan 789:807 the sulfated mannan 789:807 Polymers such as the sulfated mannan could be a helpful source of hemostatic agents to prevent hemorrhagic states. 26572344 6 27 theme helpful 820:826 arg1 Polymers 772:779 Polymers 772:779 Polymers such as the sulfated mannan 772:807 Polymers such as the sulfated mannan could be a helpful source of hemostatic agents to prevent hemorrhagic states. 26572344 3 28 with desulfation 391:401 arg1 iodomethane 438:448 trideuterated iodomethane 424:448 trideuterated iodomethane 424:448 A mannan with a main chain of α-(1 → 6)-linked-Manp units, branched at O-2 mainly by side-chains of 2-O-linked-α-Manp units was chemically sulfated, structurally characterized by NMR and GC-MS (methylation, desulfation and methylation with trideuterated iodomethane), and tested in vitro and in vivo on blood coagulation models. 26572344 5 29 theme blood 657:661 arg1 coagulation 663:673 blood coagulation 657:673 blood coagulation 657:673 This polymer acted as a procoagulant agent, increasing blood coagulation in normal and hemophilic plasma, activated platelet aggregation and also decreased ex vivo aPTT. 26572344 3 30 with mannan 186:191 arg1 chain 205:209 a main chain 198:209 a main chain of α-(1 → 6)-linked-Manp units, branched at O-2 mainly by side-chains of 2-O-linked-α-Manp units 198:306 A mannan with a main chain of α-(1 → 6)-linked-Manp units, branched at O-2 mainly by side-chains of 2-O-linked-α-Manp units was chemically sulfated, structurally characterized by NMR and GC-MS (methylation, desulfation and methylation with trideuterated iodomethane), and tested in vitro and in vivo on blood coagulation models. 26572344 3 31 with methylation 407:417 arg1 iodomethane 438:448 trideuterated iodomethane 424:448 trideuterated iodomethane 424:448 A mannan with a main chain of α-(1 → 6)-linked-Manp units, branched at O-2 mainly by side-chains of 2-O-linked-α-Manp units was chemically sulfated, structurally characterized by NMR and GC-MS (methylation, desulfation and methylation with trideuterated iodomethane), and tested in vitro and in vivo on blood coagulation models. 26572344 1 32 theme innumerous 79:88 arg1 problems 90:97 innumerous problems 79:97 innumerous problems 79:97 Disorders of hemostasis can produce innumerous problems. 26572344 5 33 from coagulation 663:673 arg1 plasma 700:705 normal and hemophilic plasma 678:705 normal and hemophilic plasma 678:705 This polymer acted as a procoagulant agent, increasing blood coagulation in normal and hemophilic plasma, activated platelet aggregation and also decreased ex vivo aPTT. 26572344 3 34 theme units 302:306 arg1 side-chains 269:279 side-chains 269:279 side-chains of 2-O-linked-α-Manp units 269:306 A mannan with a main chain of α-(1 → 6)-linked-Manp units, branched at O-2 mainly by side-chains of 2-O-linked-α-Manp units was chemically sulfated, structurally characterized by NMR and GC-MS (methylation, desulfation and methylation with trideuterated iodomethane), and tested in vitro and in vivo on blood coagulation models. 26572344 6 35 theme sulfated 793:800 arg1 mannan 802:807 the sulfated mannan 789:807 the sulfated mannan 789:807 Polymers such as the sulfated mannan could be a helpful source of hemostatic agents to prevent hemorrhagic states. 26572344 4 36 theme sulfated 577:584 arg1 polysaccharide 586:599 the sulfated polysaccharide 573:599 the sulfated polysaccharide 573:599 Chemical analyses indicate a high degree of substitution on the sulfated polysaccharide. 25774941 7 0 theme protein 994:1000 arg1 control 1010:1016 protein quality control 994:1016 protein quality control 994:1016 These findings set the stage to assess whether O-GlcNAcylation has a role in protein quality control in a manner that bears similarity with the role played by N-glycosylation within the secretory pathway. 25774941 1 1 gly glycosylation 93:105 arg1 proteins 110:117 proteins 110:117 proteins 110:117 Nucleocytoplasmic glycosylation of proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) is recognized as a conserved post-translational modification found in all metazoans. 25774941 7 2 from role 986:989 arg1 control 1010:1016 protein quality control 994:1016 protein quality control 994:1016 These findings set the stage to assess whether O-GlcNAcylation has a role in protein quality control in a manner that bears similarity with the role played by N-glycosylation within the secretory pathway. 25774941 5 3 theme cotranslational 675:689 arg1 ubiquitylation 691:704 cotranslational ubiquitylation 675:704 cotranslational ubiquitylation 675:704 This process protects nascent polypeptide chains from premature degradation by decreasing cotranslational ubiquitylation. 25774941 1 4 theme Nucleocytoplasmic 75:91 arg1 glycosylation 93:105 Nucleocytoplasmic glycosylation 75:105 Nucleocytoplasmic glycosylation of proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) 75:171 Nucleocytoplasmic glycosylation of proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) is recognized as a conserved post-translational modification found in all metazoans. 25774941 1 4 theme Nucleocytoplasmic 75:91 arg1 modification 221:232 a conserved post-translational modification 190:232 a conserved post-translational modification found in all metazoans 190:255 Nucleocytoplasmic glycosylation of proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) is recognized as a conserved post-translational modification found in all metazoans. 25774941 6 5 theme cotranslational 798:812 arg1 O-GlcNAcylation 814:828 cotranslational O-GlcNAcylation 798:828 cotranslational O-GlcNAcylation 798:828 Given that hundreds of proteins are O-GlcNAcylated within cells, our findings suggest that cotranslational O-GlcNAcylation may be a phenomenon regulating proteostasis of an array of nucleocytoplasmic proteins. 25774941 6 5 theme cotranslational 798:812 arg1 phenomenon 839:848 a phenomenon 837:848 a phenomenon regulating proteostasis of an array of nucleocytoplasmic proteins 837:914 Given that hundreds of proteins are O-GlcNAcylated within cells, our findings suggest that cotranslational O-GlcNAcylation may be a phenomenon regulating proteostasis of an array of nucleocytoplasmic proteins. 25774941 6 6 theme proteins 907:914 arg1 array 880:884 an array 877:884 an array of nucleocytoplasmic proteins 877:914 Given that hundreds of proteins are O-GlcNAcylated within cells, our findings suggest that cotranslational O-GlcNAcylation may be a phenomenon regulating proteostasis of an array of nucleocytoplasmic proteins. 25774941 7 7 theme quality 1002:1008 arg1 control 1010:1016 protein quality control 994:1016 protein quality control 994:1016 These findings set the stage to assess whether O-GlcNAcylation has a role in protein quality control in a manner that bears similarity with the role played by N-glycosylation within the secretory pathway. 25774941 1 8 theme conserved 192:200 arg1 modification 221:232 a conserved post-translational modification 190:232 a conserved post-translational modification found in all metazoans 190:255 Nucleocytoplasmic glycosylation of proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) is recognized as a conserved post-translational modification found in all metazoans. 25774941 1 8 theme conserved 192:200 arg1 glycosylation 93:105 Nucleocytoplasmic glycosylation 75:105 Nucleocytoplasmic glycosylation of proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) 75:171 Nucleocytoplasmic glycosylation of proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) is recognized as a conserved post-translational modification found in all metazoans. 25774941 0 9 theme nascent 47:53 arg1 chains 67:72 nascent polypeptide chains 47:72 nascent polypeptide chains 47:72 O-GlcNAc occurs cotranslationally to stabilize nascent polypeptide chains. 25774941 6 10 theme nucleocytoplasmic 889:905 arg1 proteins 907:914 nucleocytoplasmic proteins 889:914 nucleocytoplasmic proteins 889:914 Given that hundreds of proteins are O-GlcNAcylated within cells, our findings suggest that cotranslational O-GlcNAcylation may be a phenomenon regulating proteostasis of an array of nucleocytoplasmic proteins. 25774941 1 11 theme post-translational 202:219 arg1 modification 221:232 a conserved post-translational modification 190:232 a conserved post-translational modification found in all metazoans 190:255 Nucleocytoplasmic glycosylation of proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) is recognized as a conserved post-translational modification found in all metazoans. 25774941 1 11 theme post-translational 202:219 arg1 glycosylation 93:105 Nucleocytoplasmic glycosylation 75:105 Nucleocytoplasmic glycosylation of proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) 75:171 Nucleocytoplasmic glycosylation of proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) is recognized as a conserved post-translational modification found in all metazoans. 25774941 1 12 theme proteins 110:117 arg1 glycosylation 93:105 Nucleocytoplasmic glycosylation 75:105 Nucleocytoplasmic glycosylation of proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) 75:171 Nucleocytoplasmic glycosylation of proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) is recognized as a conserved post-translational modification found in all metazoans. 25774941 1 12 theme proteins 110:117 arg1 modification 221:232 a conserved post-translational modification 190:232 a conserved post-translational modification found in all metazoans 190:255 Nucleocytoplasmic glycosylation of proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) is recognized as a conserved post-translational modification found in all metazoans. 25774941 5 13 theme premature 639:647 arg1 degradation 649:659 premature degradation 639:659 premature degradation 639:659 This process protects nascent polypeptide chains from premature degradation by decreasing cotranslational ubiquitylation. 25774941 3 14 theme various 412:418 arg1 proteins 420:427 various proteins 412:427 various proteins 412:427 Impaired cellular O-GlcNAcylation has been found to lead to decreases in the levels of various proteins, which is one mechanism by which O-GlcNAc seems to exert its varied physiological effects. 25774941 6 15 theme array 880:884 arg1 proteostasis 861:872 proteostasis 861:872 proteostasis of an array of nucleocytoplasmic proteins 861:914 Given that hundreds of proteins are O-GlcNAcylated within cells, our findings suggest that cotranslational O-GlcNAcylation may be a phenomenon regulating proteostasis of an array of nucleocytoplasmic proteins. 25774941 3 16 theme Impaired 325:332 arg1 O-GlcNAcylation 343:357 Impaired cellular O-GlcNAcylation 325:357 Impaired cellular O-GlcNAcylation 325:357 Impaired cellular O-GlcNAcylation has been found to lead to decreases in the levels of various proteins, which is one mechanism by which O-GlcNAc seems to exert its varied physiological effects. 25774941 1 17 theme O-linked 124:131 arg1 O-GlcNAc 163:170 O-GlcNAc 163:170 O-GlcNAc 163:170 Nucleocytoplasmic glycosylation of proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) is recognized as a conserved post-translational modification found in all metazoans. 25774941 1 17 theme O-linked 124:131 arg1 residues 153:160 O-linked N-acetylglucosamine residues 124:160 O-linked N-acetylglucosamine residues (O-GlcNAc) 124:171 Nucleocytoplasmic glycosylation of proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) is recognized as a conserved post-translational modification found in all metazoans. 25774941 3 18 theme varied 490:495 arg1 effects 511:517 its varied physiological effects 486:517 its varied physiological effects 486:517 Impaired cellular O-GlcNAcylation has been found to lead to decreases in the levels of various proteins, which is one mechanism by which O-GlcNAc seems to exert its varied physiological effects. 25774941 3 19 theme proteins 420:427 arg1 levels 402:407 the levels 398:407 the levels of various proteins, which is one mechanism by which O-GlcNAc seems to exert its varied physiological effects 398:517 Impaired cellular O-GlcNAcylation has been found to lead to decreases in the levels of various proteins, which is one mechanism by which O-GlcNAc seems to exert its varied physiological effects. 25774941 3 20 theme cellular 334:341 arg1 O-GlcNAcylation 343:357 Impaired cellular O-GlcNAcylation 325:357 Impaired cellular O-GlcNAcylation 325:357 Impaired cellular O-GlcNAcylation has been found to lead to decreases in the levels of various proteins, which is one mechanism by which O-GlcNAc seems to exert its varied physiological effects. 25774941 1 21 theme N-acetylglucosamine 133:151 arg1 O-GlcNAc 163:170 O-GlcNAc 163:170 O-GlcNAc 163:170 Nucleocytoplasmic glycosylation of proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) is recognized as a conserved post-translational modification found in all metazoans. 25774941 1 21 theme N-acetylglucosamine 133:151 arg1 residues 153:160 O-linked N-acetylglucosamine residues 124:160 O-linked N-acetylglucosamine residues (O-GlcNAc) 124:171 Nucleocytoplasmic glycosylation of proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) is recognized as a conserved post-translational modification found in all metazoans. 25774941 1 22 with glycosylation 93:105 arg1 O-GlcNAc 163:170 O-GlcNAc 163:170 O-GlcNAc 163:170 Nucleocytoplasmic glycosylation of proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) is recognized as a conserved post-translational modification found in all metazoans. 25774941 1 22 with glycosylation 93:105 arg1 residues 153:160 O-linked N-acetylglucosamine residues 124:160 O-linked N-acetylglucosamine residues (O-GlcNAc) 124:171 Nucleocytoplasmic glycosylation of proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) is recognized as a conserved post-translational modification found in all metazoans. 25774941 7 23 with similarity 1041:1050 arg1 role 1061:1064 the role 1057:1064 the role played by N-glycosylation within the secretory pathway 1057:1119 These findings set the stage to assess whether O-GlcNAcylation has a role in protein quality control in a manner that bears similarity with the role played by N-glycosylation within the secretory pathway. 25774941 1 24 located found 234:238 arg2 glycosylation 93:105 Nucleocytoplasmic glycosylation 75:105 Nucleocytoplasmic glycosylation of proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) 75:171 Nucleocytoplasmic glycosylation of proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) is recognized as a conserved post-translational modification found in all metazoans. 25774941 1 24 located found 234:238 arg1 metazoans 247:255 all metazoans 243:255 all metazoans 243:255 Nucleocytoplasmic glycosylation of proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) is recognized as a conserved post-translational modification found in all metazoans. 25774941 1 24 located found 234:238 arg2 modification 221:232 a conserved post-translational modification 190:232 a conserved post-translational modification found in all metazoans 190:255 Nucleocytoplasmic glycosylation of proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) is recognized as a conserved post-translational modification found in all metazoans. 25774941 7 25 theme secretory 1103:1111 arg1 pathway 1113:1119 the secretory pathway 1099:1119 the secretory pathway 1099:1119 These findings set the stage to assess whether O-GlcNAcylation has a role in protein quality control in a manner that bears similarity with the role played by N-glycosylation within the secretory pathway. 25774941 0 26 theme polypeptide 55:65 arg1 chains 67:72 nascent polypeptide chains 47:72 nascent polypeptide chains 47:72 O-GlcNAc occurs cotranslationally to stabilize nascent polypeptide chains. 25774941 5 27 theme nascent 607:613 arg1 chains 627:632 nascent polypeptide chains 607:632 nascent polypeptide chains 607:632 This process protects nascent polypeptide chains from premature degradation by decreasing cotranslational ubiquitylation. 25774941 7 28 contain has 980:982 arg1 O-GlcNAcylation 964:978 O-GlcNAcylation 964:978 O-GlcNAcylation 964:978 These findings set the stage to assess whether O-GlcNAcylation has a role in protein quality control in a manner that bears similarity with the role played by N-glycosylation within the secretory pathway. 25774941 7 28 contain has 980:982 arg2 role 986:989 a role 984:989 a role in protein quality control 984:1016 These findings set the stage to assess whether O-GlcNAcylation has a role in protein quality control in a manner that bears similarity with the role played by N-glycosylation within the secretory pathway. 25774941 2 29 theme cellular 305:312 arg1 processes 314:322 diverse cellular processes 297:322 diverse cellular processes 297:322 O-GlcNAc has been proposed to regulate diverse cellular processes. 25774941 5 30 theme polypeptide 615:625 arg1 chains 627:632 nascent polypeptide chains 607:632 nascent polypeptide chains 607:632 This process protects nascent polypeptide chains from premature degradation by decreasing cotranslational ubiquitylation. 25774941 2 31 theme diverse 297:303 arg1 processes 314:322 diverse cellular processes 297:322 diverse cellular processes 297:322 O-GlcNAc has been proposed to regulate diverse cellular processes. 25774941 6 32 theme proteins 730:737 arg1 hundreds 718:725 hundreds 718:725 hundreds of proteins 718:737 Given that hundreds of proteins are O-GlcNAcylated within cells, our findings suggest that cotranslational O-GlcNAcylation may be a phenomenon regulating proteostasis of an array of nucleocytoplasmic proteins. 25774941 1 33 link O-linked 124:131 arg1 O-GlcNAc 163:170 O-GlcNAc 163:170 O-GlcNAc 163:170 Nucleocytoplasmic glycosylation of proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) is recognized as a conserved post-translational modification found in all metazoans. 25774941 1 33 link O-linked 124:131 arg1 residues 153:160 O-linked N-acetylglucosamine residues 124:160 O-linked N-acetylglucosamine residues (O-GlcNAc) 124:171 Nucleocytoplasmic glycosylation of proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) is recognized as a conserved post-translational modification found in all metazoans. 25774941 3 34 from decreases 385:393 arg1 levels 402:407 the levels 398:407 the levels of various proteins, which is one mechanism by which O-GlcNAc seems to exert its varied physiological effects 398:517 Impaired cellular O-GlcNAcylation has been found to lead to decreases in the levels of various proteins, which is one mechanism by which O-GlcNAc seems to exert its varied physiological effects. 25774941 3 35 dep varied 490:495 arg1 physiological 497:509 physiological 497:509 physiological 497:509 Impaired cellular O-GlcNAcylation has been found to lead to decreases in the levels of various proteins, which is one mechanism by which O-GlcNAc seems to exert its varied physiological effects. 25774941 7 36 contain bears 1035:1039 arg1 manner 1023:1028 a manner 1021:1028 a manner that bears similarity with the role played by N-glycosylation within the secretory pathway 1021:1119 These findings set the stage to assess whether O-GlcNAcylation has a role in protein quality control in a manner that bears similarity with the role played by N-glycosylation within the secretory pathway. 25774941 7 36 contain bears 1035:1039 arg2 similarity 1041:1050 similarity 1041:1050 similarity with the role played by N-glycosylation within the secretory pathway 1041:1119 These findings set the stage to assess whether O-GlcNAcylation has a role in protein quality control in a manner that bears similarity with the role played by N-glycosylation within the secretory pathway. 25654559 1 0 theme liver 159:163 arg1 tissue 165:170 mouse liver tissue 153:170 mouse liver tissue 153:170 Beam-type collision-induced dissociation (CID) data of intact glycopeptides isolated from mouse liver tissue are presented to illustrate characteristic fragmentation of differentially sialylated glycopeptides. 25654559 4 1 theme retention 847:855 arg1 times 857:861 slightly reduced retention times 830:861 slightly reduced retention times 830:861 We show how changes in sialic acid composition affect reverse phase chromatographic retention times: sialic acid addition increases glycopeptide retention times significantly; replacing the N-acetylneuraminic acid with the N-glycolyl variant leads to slightly reduced retention times, while O-acetylated sialic acid-containing glycoforms are retained longer. 25654559 5 2 theme diagnostic 1008:1017 arg1 ions 1027:1030 these diagnostic oxonium ions 1002:1030 these diagnostic oxonium ions 1002:1030 We then demonstrate how MS-Filter in Protein Prospector can use these diagnostic oxonium ions to find glycopeptides, by showing that a wealth of different glycopeptides can be found in a published phosphopeptide data set. 25654559 1 3 attach isolated 139:146 arg1 tissue 165:170 mouse liver tissue 153:170 mouse liver tissue 153:170 Beam-type collision-induced dissociation (CID) data of intact glycopeptides isolated from mouse liver tissue are presented to illustrate characteristic fragmentation of differentially sialylated glycopeptides. 25654559 1 3 attach isolated 139:146 arg2 glycopeptides 125:137 intact glycopeptides 118:137 intact glycopeptides isolated from mouse liver tissue 118:170 Beam-type collision-induced dissociation (CID) data of intact glycopeptides isolated from mouse liver tissue are presented to illustrate characteristic fragmentation of differentially sialylated glycopeptides. 25654559 4 4 gly glycopeptide 711:722 arg2 glycopeptide 711:722 glycopeptide retention times 711:738 glycopeptide retention times 711:738 We show how changes in sialic acid composition affect reverse phase chromatographic retention times: sialic acid addition increases glycopeptide retention times significantly; replacing the N-acetylneuraminic acid with the N-glycolyl variant leads to slightly reduced retention times, while O-acetylated sialic acid-containing glycoforms are retained longer. 25654559 1 5 gly glycopeptides 258:270 arg2 glycopeptides 258:270 differentially sialylated glycopeptides 232:270 differentially sialylated glycopeptides 232:270 Beam-type collision-induced dissociation (CID) data of intact glycopeptides isolated from mouse liver tissue are presented to illustrate characteristic fragmentation of differentially sialylated glycopeptides. 25654559 4 6 theme acid 609:612 arg1 composition 614:624 sialic acid composition 602:624 sialic acid composition 602:624 We show how changes in sialic acid composition affect reverse phase chromatographic retention times: sialic acid addition increases glycopeptide retention times significantly; replacing the N-acetylneuraminic acid with the N-glycolyl variant leads to slightly reduced retention times, while O-acetylated sialic acid-containing glycoforms are retained longer. 25654559 1 7 gly sialylated 247:256 arg1 glycopeptides 258:270 differentially sialylated glycopeptides 232:270 differentially sialylated glycopeptides 232:270 Beam-type collision-induced dissociation (CID) data of intact glycopeptides isolated from mouse liver tissue are presented to illustrate characteristic fragmentation of differentially sialylated glycopeptides. 25654559 4 8 theme reduced 839:845 arg1 times 857:861 slightly reduced retention times 830:861 slightly reduced retention times 830:861 We show how changes in sialic acid composition affect reverse phase chromatographic retention times: sialic acid addition increases glycopeptide retention times significantly; replacing the N-acetylneuraminic acid with the N-glycolyl variant leads to slightly reduced retention times, while O-acetylated sialic acid-containing glycoforms are retained longer. 25654559 2 9 link O-linked 296:303 arg1 glycopeptide 305:316 an O-linked glycopeptide 293:316 an O-linked glycopeptide from Nucleobindin-1 293:336 Eight glycoforms of an O-linked glycopeptide from Nucleobindin-1 are distinguished on the basis of the precursor masses and characteristic oxonium ions. 25654559 1 10 theme Beam-type 63:71 arg1 CID 105:107 CID 105:107 CID 105:107 Beam-type collision-induced dissociation (CID) data of intact glycopeptides isolated from mouse liver tissue are presented to illustrate characteristic fragmentation of differentially sialylated glycopeptides. 25654559 1 10 theme Beam-type 63:71 arg1 dissociation 91:102 Beam-type collision-induced dissociation 63:102 Beam-type collision-induced dissociation (CID) data of intact glycopeptides isolated from mouse liver tissue 63:170 Beam-type collision-induced dissociation (CID) data of intact glycopeptides isolated from mouse liver tissue are presented to illustrate characteristic fragmentation of differentially sialylated glycopeptides. 25654559 2 11 gly glycopeptide 305:316 arg1 Nucleobindin-1 323:336 Nucleobindin-1 323:336 Nucleobindin-1 323:336 Eight glycoforms of an O-linked glycopeptide from Nucleobindin-1 are distinguished on the basis of the precursor masses and characteristic oxonium ions. 25654559 2 11 gly glycopeptide 305:316 arg2 glycopeptide 305:316 an O-linked glycopeptide 293:316 an O-linked glycopeptide from Nucleobindin-1 293:336 Eight glycoforms of an O-linked glycopeptide from Nucleobindin-1 are distinguished on the basis of the precursor masses and characteristic oxonium ions. 25654559 3 12 theme charge 501:506 arg1 species 516:522 the charge reduced species 497:522 the charge reduced species 497:522 We report that all sialic acid variants are prone to neutral loss from the charge reduced species in electron-transfer dissociation (ETD) fragmentation. 25654559 1 13 theme collision-induced 73:89 arg1 CID 105:107 CID 105:107 CID 105:107 Beam-type collision-induced dissociation (CID) data of intact glycopeptides isolated from mouse liver tissue are presented to illustrate characteristic fragmentation of differentially sialylated glycopeptides. 25654559 1 13 theme collision-induced 73:89 arg1 dissociation 91:102 Beam-type collision-induced dissociation 63:102 Beam-type collision-induced dissociation (CID) data of intact glycopeptides isolated from mouse liver tissue 63:170 Beam-type collision-induced dissociation (CID) data of intact glycopeptides isolated from mouse liver tissue are presented to illustrate characteristic fragmentation of differentially sialylated glycopeptides. 25654559 5 14 theme oxonium 1019:1025 arg1 ions 1027:1030 these diagnostic oxonium ions 1002:1030 these diagnostic oxonium ions 1002:1030 We then demonstrate how MS-Filter in Protein Prospector can use these diagnostic oxonium ions to find glycopeptides, by showing that a wealth of different glycopeptides can be found in a published phosphopeptide data set. 25654559 4 15 theme glycopeptide 711:722 arg1 times 734:738 glycopeptide retention times 711:738 glycopeptide retention times 711:738 We show how changes in sialic acid composition affect reverse phase chromatographic retention times: sialic acid addition increases glycopeptide retention times significantly; replacing the N-acetylneuraminic acid with the N-glycolyl variant leads to slightly reduced retention times, while O-acetylated sialic acid-containing glycoforms are retained longer. 25654559 3 16 theme sialic 445:450 arg1 variants 457:464 all sialic acid variants 441:464 all sialic acid variants 441:464 We report that all sialic acid variants are prone to neutral loss from the charge reduced species in electron-transfer dissociation (ETD) fragmentation. 25654559 3 17 theme acid 452:455 arg1 variants 457:464 all sialic acid variants 441:464 all sialic acid variants 441:464 We report that all sialic acid variants are prone to neutral loss from the charge reduced species in electron-transfer dissociation (ETD) fragmentation. 25654559 1 18 theme dissociation 91:102 arg1 data 110:113 Beam-type collision-induced dissociation (CID) data 63:113 Beam-type collision-induced dissociation (CID) data of intact glycopeptides isolated from mouse liver tissue 63:170 Beam-type collision-induced dissociation (CID) data of intact glycopeptides isolated from mouse liver tissue are presented to illustrate characteristic fragmentation of differentially sialylated glycopeptides. 25654559 5 19 gly glycopeptides 1040:1052 arg2 glycopeptides 1040:1052 glycopeptides 1040:1052 glycopeptides 1040:1052 We then demonstrate how MS-Filter in Protein Prospector can use these diagnostic oxonium ions to find glycopeptides, by showing that a wealth of different glycopeptides can be found in a published phosphopeptide data set. 25654559 3 20 theme neutral 479:485 arg1 loss 487:490 neutral loss 479:490 neutral loss from the charge reduced species in electron-transfer dissociation (ETD) fragmentation 479:576 We report that all sialic acid variants are prone to neutral loss from the charge reduced species in electron-transfer dissociation (ETD) fragmentation. 25654559 0 21 theme sialic 15:20 arg1 variants 27:34 sialic acid variants 15:34 sialic acid variants 15:34 Characterizing sialic acid variants at the glycopeptide level. 25654559 3 22 from species 516:522 arg1 loss 487:490 neutral loss 479:490 neutral loss from the charge reduced species in electron-transfer dissociation (ETD) fragmentation 479:576 We report that all sialic acid variants are prone to neutral loss from the charge reduced species in electron-transfer dissociation (ETD) fragmentation. 25654559 4 23 theme N-glycolyl 802:811 arg1 variant 813:819 the N-glycolyl variant 798:819 the N-glycolyl variant 798:819 We show how changes in sialic acid composition affect reverse phase chromatographic retention times: sialic acid addition increases glycopeptide retention times significantly; replacing the N-acetylneuraminic acid with the N-glycolyl variant leads to slightly reduced retention times, while O-acetylated sialic acid-containing glycoforms are retained longer. 25654559 4 24 theme retention 724:732 arg1 times 734:738 glycopeptide retention times 711:738 glycopeptide retention times 711:738 We show how changes in sialic acid composition affect reverse phase chromatographic retention times: sialic acid addition increases glycopeptide retention times significantly; replacing the N-acetylneuraminic acid with the N-glycolyl variant leads to slightly reduced retention times, while O-acetylated sialic acid-containing glycoforms are retained longer. 25654559 2 25 gly glycoforms 279:288 arg1 glycopeptide 305:316 an O-linked glycopeptide 293:316 an O-linked glycopeptide from Nucleobindin-1 293:336 Eight glycoforms of an O-linked glycopeptide from Nucleobindin-1 are distinguished on the basis of the precursor masses and characteristic oxonium ions. 25654559 4 26 theme sialic 883:888 arg1 glycoforms 906:915 O-acetylated sialic acid-containing glycoforms 870:915 O-acetylated sialic acid-containing glycoforms 870:915 We show how changes in sialic acid composition affect reverse phase chromatographic retention times: sialic acid addition increases glycopeptide retention times significantly; replacing the N-acetylneuraminic acid with the N-glycolyl variant leads to slightly reduced retention times, while O-acetylated sialic acid-containing glycoforms are retained longer. 25654559 5 27 theme different 1083:1091 arg1 glycopeptides 1093:1105 different glycopeptides 1083:1105 different glycopeptides 1083:1105 We then demonstrate how MS-Filter in Protein Prospector can use these diagnostic oxonium ions to find glycopeptides, by showing that a wealth of different glycopeptides can be found in a published phosphopeptide data set. 25654559 2 28 from glycoforms 279:288 arg1 Nucleobindin-1 323:336 Nucleobindin-1 323:336 Nucleobindin-1 323:336 Eight glycoforms of an O-linked glycopeptide from Nucleobindin-1 are distinguished on the basis of the precursor masses and characteristic oxonium ions. 25654559 1 29 theme characteristic 200:213 arg1 fragmentation 215:227 characteristic fragmentation 200:227 characteristic fragmentation of differentially sialylated glycopeptides 200:270 Beam-type collision-induced dissociation (CID) data of intact glycopeptides isolated from mouse liver tissue are presented to illustrate characteristic fragmentation of differentially sialylated glycopeptides. 25654559 0 30 theme acid 22:25 arg1 variants 27:34 sialic acid variants 15:34 sialic acid variants 15:34 Characterizing sialic acid variants at the glycopeptide level. 25654559 4 31 theme sialic 602:607 arg1 composition 614:624 sialic acid composition 602:624 sialic acid composition 602:624 We show how changes in sialic acid composition affect reverse phase chromatographic retention times: sialic acid addition increases glycopeptide retention times significantly; replacing the N-acetylneuraminic acid with the N-glycolyl variant leads to slightly reduced retention times, while O-acetylated sialic acid-containing glycoforms are retained longer. 25654559 4 32 theme chromatographic 647:661 arg1 times 673:677 reverse phase chromatographic retention times 633:677 reverse phase chromatographic retention times 633:677 We show how changes in sialic acid composition affect reverse phase chromatographic retention times: sialic acid addition increases glycopeptide retention times significantly; replacing the N-acetylneuraminic acid with the N-glycolyl variant leads to slightly reduced retention times, while O-acetylated sialic acid-containing glycoforms are retained longer. 25654559 3 33 theme electron-transfer 527:543 arg1 fragmentation 564:576 electron-transfer dissociation (ETD) fragmentation 527:576 electron-transfer dissociation (ETD) fragmentation 527:576 We report that all sialic acid variants are prone to neutral loss from the charge reduced species in electron-transfer dissociation (ETD) fragmentation. 25654559 3 34 theme ETD 559:561 arg1 fragmentation 564:576 electron-transfer dissociation (ETD) fragmentation 527:576 electron-transfer dissociation (ETD) fragmentation 527:576 We report that all sialic acid variants are prone to neutral loss from the charge reduced species in electron-transfer dissociation (ETD) fragmentation. 25654559 3 35 theme dissociation 545:556 arg1 fragmentation 564:576 electron-transfer dissociation (ETD) fragmentation 527:576 electron-transfer dissociation (ETD) fragmentation 527:576 We report that all sialic acid variants are prone to neutral loss from the charge reduced species in electron-transfer dissociation (ETD) fragmentation. 25654559 2 36 theme precursor 376:384 arg1 masses 386:391 the precursor masses 372:391 the precursor masses 372:391 Eight glycoforms of an O-linked glycopeptide from Nucleobindin-1 are distinguished on the basis of the precursor masses and characteristic oxonium ions. 25654559 2 37 theme characteristic 397:410 arg1 ions 420:423 characteristic oxonium ions 397:423 characteristic oxonium ions 397:423 Eight glycoforms of an O-linked glycopeptide from Nucleobindin-1 are distinguished on the basis of the precursor masses and characteristic oxonium ions. 25654559 1 38 gly glycopeptides 125:137 arg2 glycopeptides 125:137 intact glycopeptides 118:137 intact glycopeptides isolated from mouse liver tissue 118:170 Beam-type collision-induced dissociation (CID) data of intact glycopeptides isolated from mouse liver tissue are presented to illustrate characteristic fragmentation of differentially sialylated glycopeptides. 25654559 4 39 theme N-acetylneuraminic 769:786 arg1 acid 788:791 the N-acetylneuraminic acid 765:791 the N-acetylneuraminic acid 765:791 We show how changes in sialic acid composition affect reverse phase chromatographic retention times: sialic acid addition increases glycopeptide retention times significantly; replacing the N-acetylneuraminic acid with the N-glycolyl variant leads to slightly reduced retention times, while O-acetylated sialic acid-containing glycoforms are retained longer. 25654559 4 40 theme acid-containing 890:904 arg1 glycoforms 906:915 O-acetylated sialic acid-containing glycoforms 870:915 O-acetylated sialic acid-containing glycoforms 870:915 We show how changes in sialic acid composition affect reverse phase chromatographic retention times: sialic acid addition increases glycopeptide retention times significantly; replacing the N-acetylneuraminic acid with the N-glycolyl variant leads to slightly reduced retention times, while O-acetylated sialic acid-containing glycoforms are retained longer. 25654559 3 41 from loss 487:490 arg1 fragmentation 564:576 electron-transfer dissociation (ETD) fragmentation 527:576 electron-transfer dissociation (ETD) fragmentation 527:576 We report that all sialic acid variants are prone to neutral loss from the charge reduced species in electron-transfer dissociation (ETD) fragmentation. 25654559 4 42 theme acid 687:690 arg1 addition 692:699 sialic acid addition 680:699 sialic acid addition 680:699 We show how changes in sialic acid composition affect reverse phase chromatographic retention times: sialic acid addition increases glycopeptide retention times significantly; replacing the N-acetylneuraminic acid with the N-glycolyl variant leads to slightly reduced retention times, while O-acetylated sialic acid-containing glycoforms are retained longer. 25654559 5 43 gly glycopeptides 1093:1105 arg2 glycopeptides 1093:1105 different glycopeptides 1083:1105 different glycopeptides 1083:1105 We then demonstrate how MS-Filter in Protein Prospector can use these diagnostic oxonium ions to find glycopeptides, by showing that a wealth of different glycopeptides can be found in a published phosphopeptide data set. 25654559 5 44 theme Protein 975:981 arg1 Prospector 983:992 Protein Prospector 975:992 Protein Prospector 975:992 We then demonstrate how MS-Filter in Protein Prospector can use these diagnostic oxonium ions to find glycopeptides, by showing that a wealth of different glycopeptides can be found in a published phosphopeptide data set. 25654559 5 45 located found 1114:1118 arg2 wealth 1073:1078 a wealth 1071:1078 a wealth of different glycopeptides 1071:1105 We then demonstrate how MS-Filter in Protein Prospector can use these diagnostic oxonium ions to find glycopeptides, by showing that a wealth of different glycopeptides can be found in a published phosphopeptide data set. 25654559 5 45 located found 1114:1118 arg1 set 1155:1157 a published phosphopeptide data set 1123:1157 a published phosphopeptide data set 1123:1157 We then demonstrate how MS-Filter in Protein Prospector can use these diagnostic oxonium ions to find glycopeptides, by showing that a wealth of different glycopeptides can be found in a published phosphopeptide data set. 25654559 2 46 theme masses 386:391 arg1 basis 363:367 the basis 359:367 the basis of the precursor masses and characteristic oxonium ions 359:423 Eight glycoforms of an O-linked glycopeptide from Nucleobindin-1 are distinguished on the basis of the precursor masses and characteristic oxonium ions. 25654559 0 47 theme glycopeptide 43:54 arg1 level 56:60 the glycopeptide level 39:60 the glycopeptide level 39:60 Characterizing sialic acid variants at the glycopeptide level. 25654559 3 48 theme reduced 508:514 arg1 species 516:522 the charge reduced species 497:522 the charge reduced species 497:522 We report that all sialic acid variants are prone to neutral loss from the charge reduced species in electron-transfer dissociation (ETD) fragmentation. 25654559 1 49 theme intact 118:123 arg1 glycopeptides 125:137 intact glycopeptides 118:137 intact glycopeptides isolated from mouse liver tissue 118:170 Beam-type collision-induced dissociation (CID) data of intact glycopeptides isolated from mouse liver tissue are presented to illustrate characteristic fragmentation of differentially sialylated glycopeptides. 25654559 5 50 theme glycopeptides 1093:1105 arg1 wealth 1073:1078 a wealth 1071:1078 a wealth of different glycopeptides 1071:1105 We then demonstrate how MS-Filter in Protein Prospector can use these diagnostic oxonium ions to find glycopeptides, by showing that a wealth of different glycopeptides can be found in a published phosphopeptide data set. 25654559 5 51 theme published 1125:1133 arg1 set 1155:1157 a published phosphopeptide data set 1123:1157 a published phosphopeptide data set 1123:1157 We then demonstrate how MS-Filter in Protein Prospector can use these diagnostic oxonium ions to find glycopeptides, by showing that a wealth of different glycopeptides can be found in a published phosphopeptide data set. 25654559 2 52 theme O-linked 296:303 arg1 glycopeptide 305:316 an O-linked glycopeptide 293:316 an O-linked glycopeptide from Nucleobindin-1 293:336 Eight glycoforms of an O-linked glycopeptide from Nucleobindin-1 are distinguished on the basis of the precursor masses and characteristic oxonium ions. 25654559 1 53 theme glycopeptides 125:137 arg1 data 110:113 Beam-type collision-induced dissociation (CID) data 63:113 Beam-type collision-induced dissociation (CID) data of intact glycopeptides isolated from mouse liver tissue 63:170 Beam-type collision-induced dissociation (CID) data of intact glycopeptides isolated from mouse liver tissue are presented to illustrate characteristic fragmentation of differentially sialylated glycopeptides. 25654559 1 54 theme sialylated 247:256 arg1 glycopeptides 258:270 differentially sialylated glycopeptides 232:270 differentially sialylated glycopeptides 232:270 Beam-type collision-induced dissociation (CID) data of intact glycopeptides isolated from mouse liver tissue are presented to illustrate characteristic fragmentation of differentially sialylated glycopeptides. 25654559 2 55 theme glycopeptide 305:316 arg1 glycoforms 279:288 Eight glycoforms 273:288 Eight glycoforms of an O-linked glycopeptide from Nucleobindin-1 273:336 Eight glycoforms of an O-linked glycopeptide from Nucleobindin-1 are distinguished on the basis of the precursor masses and characteristic oxonium ions. 25654559 5 56 theme phosphopeptide 1135:1148 arg1 set 1155:1157 a published phosphopeptide data set 1123:1157 a published phosphopeptide data set 1123:1157 We then demonstrate how MS-Filter in Protein Prospector can use these diagnostic oxonium ions to find glycopeptides, by showing that a wealth of different glycopeptides can be found in a published phosphopeptide data set. 25654559 5 57 from MS-Filter 962:970 arg1 Prospector 983:992 Protein Prospector 975:992 Protein Prospector 975:992 We then demonstrate how MS-Filter in Protein Prospector can use these diagnostic oxonium ions to find glycopeptides, by showing that a wealth of different glycopeptides can be found in a published phosphopeptide data set. 25654559 2 58 theme oxonium 412:418 arg1 ions 420:423 characteristic oxonium ions 397:423 characteristic oxonium ions 397:423 Eight glycoforms of an O-linked glycopeptide from Nucleobindin-1 are distinguished on the basis of the precursor masses and characteristic oxonium ions. 25654559 1 59 theme glycopeptides 258:270 arg1 fragmentation 215:227 characteristic fragmentation 200:227 characteristic fragmentation of differentially sialylated glycopeptides 200:270 Beam-type collision-induced dissociation (CID) data of intact glycopeptides isolated from mouse liver tissue are presented to illustrate characteristic fragmentation of differentially sialylated glycopeptides. 25654559 5 60 theme data 1150:1153 arg1 set 1155:1157 a published phosphopeptide data set 1123:1157 a published phosphopeptide data set 1123:1157 We then demonstrate how MS-Filter in Protein Prospector can use these diagnostic oxonium ions to find glycopeptides, by showing that a wealth of different glycopeptides can be found in a published phosphopeptide data set. 25654559 0 61 gly glycopeptide 43:54 arg2 glycopeptide 43:54 the glycopeptide level 39:60 the glycopeptide level 39:60 Characterizing sialic acid variants at the glycopeptide level. 25654559 4 62 theme sialic 680:685 arg1 addition 692:699 sialic acid addition 680:699 sialic acid addition 680:699 We show how changes in sialic acid composition affect reverse phase chromatographic retention times: sialic acid addition increases glycopeptide retention times significantly; replacing the N-acetylneuraminic acid with the N-glycolyl variant leads to slightly reduced retention times, while O-acetylated sialic acid-containing glycoforms are retained longer. 25654559 2 63 theme ions 420:423 arg1 basis 363:367 the basis 359:367 the basis of the precursor masses and characteristic oxonium ions 359:423 Eight glycoforms of an O-linked glycopeptide from Nucleobindin-1 are distinguished on the basis of the precursor masses and characteristic oxonium ions. 25654559 2 64 from Nucleobindin-1 323:336 arg1 glycopeptide 305:316 an O-linked glycopeptide 293:316 an O-linked glycopeptide from Nucleobindin-1 293:336 Eight glycoforms of an O-linked glycopeptide from Nucleobindin-1 are distinguished on the basis of the precursor masses and characteristic oxonium ions. 25654559 2 64 from Nucleobindin-1 323:336 arg1 glycoforms 279:288 Eight glycoforms 273:288 Eight glycoforms of an O-linked glycopeptide from Nucleobindin-1 273:336 Eight glycoforms of an O-linked glycopeptide from Nucleobindin-1 are distinguished on the basis of the precursor masses and characteristic oxonium ions. 25654559 4 65 from changes 591:597 arg1 composition 614:624 sialic acid composition 602:624 sialic acid composition 602:624 We show how changes in sialic acid composition affect reverse phase chromatographic retention times: sialic acid addition increases glycopeptide retention times significantly; replacing the N-acetylneuraminic acid with the N-glycolyl variant leads to slightly reduced retention times, while O-acetylated sialic acid-containing glycoforms are retained longer. 25654559 4 66 theme reverse 633:639 arg1 times 673:677 reverse phase chromatographic retention times 633:677 reverse phase chromatographic retention times 633:677 We show how changes in sialic acid composition affect reverse phase chromatographic retention times: sialic acid addition increases glycopeptide retention times significantly; replacing the N-acetylneuraminic acid with the N-glycolyl variant leads to slightly reduced retention times, while O-acetylated sialic acid-containing glycoforms are retained longer. 25654559 4 67 theme O-acetylated 870:881 arg1 glycoforms 906:915 O-acetylated sialic acid-containing glycoforms 870:915 O-acetylated sialic acid-containing glycoforms 870:915 We show how changes in sialic acid composition affect reverse phase chromatographic retention times: sialic acid addition increases glycopeptide retention times significantly; replacing the N-acetylneuraminic acid with the N-glycolyl variant leads to slightly reduced retention times, while O-acetylated sialic acid-containing glycoforms are retained longer. 25654559 4 68 theme phase 641:645 arg1 times 673:677 reverse phase chromatographic retention times 633:677 reverse phase chromatographic retention times 633:677 We show how changes in sialic acid composition affect reverse phase chromatographic retention times: sialic acid addition increases glycopeptide retention times significantly; replacing the N-acetylneuraminic acid with the N-glycolyl variant leads to slightly reduced retention times, while O-acetylated sialic acid-containing glycoforms are retained longer. 25654559 1 69 theme mouse 153:157 arg1 tissue 165:170 mouse liver tissue 153:170 mouse liver tissue 153:170 Beam-type collision-induced dissociation (CID) data of intact glycopeptides isolated from mouse liver tissue are presented to illustrate characteristic fragmentation of differentially sialylated glycopeptides. 25654559 4 70 theme retention 663:671 arg1 times 673:677 reverse phase chromatographic retention times 633:677 reverse phase chromatographic retention times 633:677 We show how changes in sialic acid composition affect reverse phase chromatographic retention times: sialic acid addition increases glycopeptide retention times significantly; replacing the N-acetylneuraminic acid with the N-glycolyl variant leads to slightly reduced retention times, while O-acetylated sialic acid-containing glycoforms are retained longer. 24806965 7 0 theme fourth 1013:1018 arg1 domain 1034:1039 the fourth transmembrane domain 1009:1039 the fourth transmembrane domain 1009:1039 A short region (residues 206-229) immediately to the C-terminal side of the fourth transmembrane domain is both necessary and sufficient for Golgi targeting. 24806965 9 1 theme integral 1313:1320 arg1 protein 1331:1337 an integral membrane protein 1310:1337 an integral membrane protein of the Golgi stack regulating Golgi-to-ER retrograde transport 1310:1400 These results establish that TMEM115 is an integral membrane protein of the Golgi stack regulating Golgi-to-ER retrograde transport and is likely to be part of the machinery of the COG complex. 24806965 9 1 theme integral 1313:1320 arg1 TMEM115 1299:1305 TMEM115 1299:1305 TMEM115 1299:1305 These results establish that TMEM115 is an integral membrane protein of the Golgi stack regulating Golgi-to-ER retrograde transport and is likely to be part of the machinery of the COG complex. 24806965 6 2 theme COG 871:873 arg1 complex 875:881 the COG complex 867:881 the COG complex 867:881 Co-immunoprecipitation and in vitro binding experiments reveals that TMEM115 interacts with the COG complex, and might self-interact to form dimers or oligomers. 24806965 1 3 theme transmembrane 148:160 arg1 proteins 162:169 transmembrane proteins 148:169 transmembrane proteins 148:169 Searching and evaluating the Human Protein Atlas for transmembrane proteins enabled us to identify an integral membrane protein, TMEM115, that is enriched in the Golgi complex. 24806965 7 4 theme transmembrane 1020:1032 arg1 domain 1034:1039 the fourth transmembrane domain 1009:1039 the fourth transmembrane domain 1009:1039 A short region (residues 206-229) immediately to the C-terminal side of the fourth transmembrane domain is both necessary and sufficient for Golgi targeting. 24806965 8 5 theme Helix 1184:1188 arg1 lectins 1148:1154 the lectins peanut agglutinin (PNA) and Helix pomatia agglutinin (HPA) 1144:1213 the lectins peanut agglutinin (PNA) and Helix pomatia agglutinin (HPA) 1144:1213 Knockdown of TMEM115 also reduces the binding of the lectins peanut agglutinin (PNA) and Helix pomatia agglutinin (HPA), suggesting an altered O-linked glycosylation profile. 24806965 8 5 theme Helix 1184:1188 arg1 HPA 1210:1212 HPA 1210:1212 HPA 1210:1212 Knockdown of TMEM115 also reduces the binding of the lectins peanut agglutinin (PNA) and Helix pomatia agglutinin (HPA), suggesting an altered O-linked glycosylation profile. 24806965 8 5 theme Helix 1184:1188 arg1 agglutinin 1198:1207 Helix pomatia agglutinin 1184:1207 Helix pomatia agglutinin (HPA) 1184:1213 Knockdown of TMEM115 also reduces the binding of the lectins peanut agglutinin (PNA) and Helix pomatia agglutinin (HPA), suggesting an altered O-linked glycosylation profile. 24806965 9 6 theme membrane 1322:1329 arg1 protein 1331:1337 an integral membrane protein 1310:1337 an integral membrane protein of the Golgi stack regulating Golgi-to-ER retrograde transport 1310:1400 These results establish that TMEM115 is an integral membrane protein of the Golgi stack regulating Golgi-to-ER retrograde transport and is likely to be part of the machinery of the COG complex. 24806965 9 6 theme membrane 1322:1329 arg1 TMEM115 1299:1305 TMEM115 1299:1305 TMEM115 1299:1305 These results establish that TMEM115 is an integral membrane protein of the Golgi stack regulating Golgi-to-ER retrograde transport and is likely to be part of the machinery of the COG complex. 24806965 0 7 theme retrograde 73:82 arg1 transport 84:92 retrograde transport 73:92 retrograde transport 73:92 TMEM115 is an integral membrane protein of the Golgi complex involved in retrograde transport. 24806965 2 8 contain has 336:338 arg2 domains 369:375 four candidate transmembrane domains 340:375 four candidate transmembrane domains located in the N-terminal region 340:408 Biochemical and cell biological analysis suggested that TMEM115 has four candidate transmembrane domains located in the N-terminal region. 24806965 2 8 contain has 336:338 arg1 TMEM115 328:334 TMEM115 328:334 TMEM115 328:334 Biochemical and cell biological analysis suggested that TMEM115 has four candidate transmembrane domains located in the N-terminal region. 24806965 5 9 theme Brefeldin-A-induced 625:643 arg1 transport 668:676 Brefeldin-A-induced Golgi-to-ER retrograde transport 625:676 Brefeldin-A-induced Golgi-to-ER retrograde transport 625:676 Functionally, TMEM115 knockdown or overexpression delays Brefeldin-A-induced Golgi-to-ER retrograde transport, phenocopying cells with mutations or silencing of the conserved oligomeric Golgi (COG) complex. 24806965 5 10 theme retrograde 657:666 arg1 transport 668:676 Brefeldin-A-induced Golgi-to-ER retrograde transport 625:676 Brefeldin-A-induced Golgi-to-ER retrograde transport 625:676 Functionally, TMEM115 knockdown or overexpression delays Brefeldin-A-induced Golgi-to-ER retrograde transport, phenocopying cells with mutations or silencing of the conserved oligomeric Golgi (COG) complex. 24806965 5 11 theme Golgi-to-ER 645:655 arg1 transport 668:676 Brefeldin-A-induced Golgi-to-ER retrograde transport 625:676 Brefeldin-A-induced Golgi-to-ER retrograde transport 625:676 Functionally, TMEM115 knockdown or overexpression delays Brefeldin-A-induced Golgi-to-ER retrograde transport, phenocopying cells with mutations or silencing of the conserved oligomeric Golgi (COG) complex. 24806965 7 12 dep residues 953:960 arg1 206-229 962:968 206-229 962:968 206-229 962:968 A short region (residues 206-229) immediately to the C-terminal side of the fourth transmembrane domain is both necessary and sufficient for Golgi targeting. 24806965 9 13 theme COG 1451:1453 arg1 complex 1455:1461 the COG complex 1447:1461 the COG complex 1447:1461 These results establish that TMEM115 is an integral membrane protein of the Golgi stack regulating Golgi-to-ER retrograde transport and is likely to be part of the machinery of the COG complex. 24806965 8 14 theme pomatia 1190:1196 arg1 lectins 1148:1154 the lectins peanut agglutinin (PNA) and Helix pomatia agglutinin (HPA) 1144:1213 the lectins peanut agglutinin (PNA) and Helix pomatia agglutinin (HPA) 1144:1213 Knockdown of TMEM115 also reduces the binding of the lectins peanut agglutinin (PNA) and Helix pomatia agglutinin (HPA), suggesting an altered O-linked glycosylation profile. 24806965 8 14 theme pomatia 1190:1196 arg1 HPA 1210:1212 HPA 1210:1212 HPA 1210:1212 Knockdown of TMEM115 also reduces the binding of the lectins peanut agglutinin (PNA) and Helix pomatia agglutinin (HPA), suggesting an altered O-linked glycosylation profile. 24806965 8 14 theme pomatia 1190:1196 arg1 agglutinin 1198:1207 Helix pomatia agglutinin 1184:1207 Helix pomatia agglutinin (HPA) 1184:1213 Knockdown of TMEM115 also reduces the binding of the lectins peanut agglutinin (PNA) and Helix pomatia agglutinin (HPA), suggesting an altered O-linked glycosylation profile. 24806965 4 15 theme Immunofluorescence 482:499 arg1 analysis 501:508 Immunofluorescence analysis 482:508 Immunofluorescence analysis 482:508 Immunofluorescence analysis supports that TMEM115 is enriched in the Golgi cisternae. 24806965 8 16 link O-linked 1238:1245 arg1 profile 1261:1267 an altered O-linked glycosylation profile 1227:1267 an altered O-linked glycosylation profile 1227:1267 Knockdown of TMEM115 also reduces the binding of the lectins peanut agglutinin (PNA) and Helix pomatia agglutinin (HPA), suggesting an altered O-linked glycosylation profile. 24806965 3 17 theme C-terminal 427:436 arg1 domains 438:444 C-terminal domains 427:444 C-terminal domains 427:444 Both the N- and C-terminal domains are oriented towards the cytoplasm. 24806965 9 18 theme Golgi 1346:1350 arg1 stack 1352:1356 the Golgi stack 1342:1356 the Golgi stack regulating Golgi-to-ER retrograde transport 1342:1400 These results establish that TMEM115 is an integral membrane protein of the Golgi stack regulating Golgi-to-ER retrograde transport and is likely to be part of the machinery of the COG complex. 24806965 8 19 theme TMEM115 1108:1114 arg1 Knockdown 1095:1103 Knockdown 1095:1103 Knockdown of TMEM115 1095:1114 Knockdown of TMEM115 also reduces the binding of the lectins peanut agglutinin (PNA) and Helix pomatia agglutinin (HPA), suggesting an altered O-linked glycosylation profile. 24806965 5 20 theme TMEM115 582:588 arg1 knockdown 590:598 TMEM115 knockdown 582:598 TMEM115 knockdown 582:598 Functionally, TMEM115 knockdown or overexpression delays Brefeldin-A-induced Golgi-to-ER retrograde transport, phenocopying cells with mutations or silencing of the conserved oligomeric Golgi (COG) complex. 24806965 2 21 theme biological 293:302 arg1 analysis 304:311 Biochemical and cell biological analysis 272:311 Biochemical and cell biological analysis 272:311 Biochemical and cell biological analysis suggested that TMEM115 has four candidate transmembrane domains located in the N-terminal region. 24806965 2 22 theme located 377:383 arg1 domains 369:375 four candidate transmembrane domains 340:375 four candidate transmembrane domains located in the N-terminal region 340:408 Biochemical and cell biological analysis suggested that TMEM115 has four candidate transmembrane domains located in the N-terminal region. 24806965 8 23 dep lectins 1148:1154 arg1 PNA 1175:1177 PNA 1175:1177 PNA 1175:1177 Knockdown of TMEM115 also reduces the binding of the lectins peanut agglutinin (PNA) and Helix pomatia agglutinin (HPA), suggesting an altered O-linked glycosylation profile. 24806965 8 23 dep lectins 1148:1154 arg1 agglutinin 1163:1172 peanut agglutinin 1156:1172 peanut agglutinin (PNA) 1156:1178 Knockdown of TMEM115 also reduces the binding of the lectins peanut agglutinin (PNA) and Helix pomatia agglutinin (HPA), suggesting an altered O-linked glycosylation profile. 24806965 8 23 dep lectins 1148:1154 arg1 lectins 1148:1154 the lectins peanut agglutinin (PNA) and Helix pomatia agglutinin (HPA) 1144:1213 the lectins peanut agglutinin (PNA) and Helix pomatia agglutinin (HPA) 1144:1213 Knockdown of TMEM115 also reduces the binding of the lectins peanut agglutinin (PNA) and Helix pomatia agglutinin (HPA), suggesting an altered O-linked glycosylation profile. 24806965 8 23 dep lectins 1148:1154 arg1 HPA 1210:1212 HPA 1210:1212 HPA 1210:1212 Knockdown of TMEM115 also reduces the binding of the lectins peanut agglutinin (PNA) and Helix pomatia agglutinin (HPA), suggesting an altered O-linked glycosylation profile. 24806965 8 23 dep lectins 1148:1154 arg1 agglutinin 1198:1207 Helix pomatia agglutinin 1184:1207 Helix pomatia agglutinin (HPA) 1184:1213 Knockdown of TMEM115 also reduces the binding of the lectins peanut agglutinin (PNA) and Helix pomatia agglutinin (HPA), suggesting an altered O-linked glycosylation profile. 24806965 9 24 theme stack 1352:1356 arg1 protein 1331:1337 an integral membrane protein 1310:1337 an integral membrane protein of the Golgi stack regulating Golgi-to-ER retrograde transport 1310:1400 These results establish that TMEM115 is an integral membrane protein of the Golgi stack regulating Golgi-to-ER retrograde transport and is likely to be part of the machinery of the COG complex. 24806965 9 24 theme stack 1352:1356 arg1 TMEM115 1299:1305 TMEM115 1299:1305 TMEM115 1299:1305 These results establish that TMEM115 is an integral membrane protein of the Golgi stack regulating Golgi-to-ER retrograde transport and is likely to be part of the machinery of the COG complex. 24806965 0 25 theme integral 14:21 arg1 protein 32:38 an integral membrane protein 11:38 an integral membrane protein of the Golgi complex involved in retrograde transport 11:92 TMEM115 is an integral membrane protein of the Golgi complex involved in retrograde transport. 24806965 0 25 theme integral 14:21 arg1 TMEM115 0:6 TMEM115 0:6 TMEM115 0:6 TMEM115 is an integral membrane protein of the Golgi complex involved in retrograde transport. 24806965 1 26 theme Golgi 257:261 arg1 complex 263:269 the Golgi complex 253:269 the Golgi complex 253:269 Searching and evaluating the Human Protein Atlas for transmembrane proteins enabled us to identify an integral membrane protein, TMEM115, that is enriched in the Golgi complex. 24806965 5 27 theme oligomeric 743:752 arg1 complex 766:772 the conserved oligomeric Golgi (COG) complex 729:772 the conserved oligomeric Golgi (COG) complex 729:772 Functionally, TMEM115 knockdown or overexpression delays Brefeldin-A-induced Golgi-to-ER retrograde transport, phenocopying cells with mutations or silencing of the conserved oligomeric Golgi (COG) complex. 24806965 7 28 theme C-terminal 990:999 arg1 side 1001:1004 the C-terminal side 986:1004 the C-terminal side of the fourth transmembrane domain 986:1039 A short region (residues 206-229) immediately to the C-terminal side of the fourth transmembrane domain is both necessary and sufficient for Golgi targeting. 24806965 9 29 theme Golgi-to-ER 1369:1379 arg1 transport 1392:1400 Golgi-to-ER retrograde transport 1369:1400 Golgi-to-ER retrograde transport 1369:1400 These results establish that TMEM115 is an integral membrane protein of the Golgi stack regulating Golgi-to-ER retrograde transport and is likely to be part of the machinery of the COG complex. 24806965 5 30 theme Golgi 754:758 arg1 complex 766:772 the conserved oligomeric Golgi (COG) complex 729:772 the conserved oligomeric Golgi (COG) complex 729:772 Functionally, TMEM115 knockdown or overexpression delays Brefeldin-A-induced Golgi-to-ER retrograde transport, phenocopying cells with mutations or silencing of the conserved oligomeric Golgi (COG) complex. 24806965 2 31 theme Biochemical 272:282 arg1 analysis 304:311 Biochemical and cell biological analysis 272:311 Biochemical and cell biological analysis 272:311 Biochemical and cell biological analysis suggested that TMEM115 has four candidate transmembrane domains located in the N-terminal region. 24806965 1 32 theme Protein 130:136 arg1 Atlas 138:142 the Human Protein Atlas 120:142 the Human Protein Atlas for transmembrane proteins 120:169 Searching and evaluating the Human Protein Atlas for transmembrane proteins enabled us to identify an integral membrane protein, TMEM115, that is enriched in the Golgi complex. 24806965 9 33 theme retrograde 1381:1390 arg1 transport 1392:1400 Golgi-to-ER retrograde transport 1369:1400 Golgi-to-ER retrograde transport 1369:1400 These results establish that TMEM115 is an integral membrane protein of the Golgi stack regulating Golgi-to-ER retrograde transport and is likely to be part of the machinery of the COG complex. 24806965 1 34 theme integral 197:204 arg1 TMEM115 224:230 TMEM115 224:230 TMEM115 224:230 Searching and evaluating the Human Protein Atlas for transmembrane proteins enabled us to identify an integral membrane protein, TMEM115, that is enriched in the Golgi complex. 24806965 1 34 theme integral 197:204 arg1 protein 215:221 an integral membrane protein 194:221 an integral membrane protein 194:221 Searching and evaluating the Human Protein Atlas for transmembrane proteins enabled us to identify an integral membrane protein, TMEM115, that is enriched in the Golgi complex. 24806965 0 35 theme membrane 23:30 arg1 protein 32:38 an integral membrane protein 11:38 an integral membrane protein of the Golgi complex involved in retrograde transport 11:92 TMEM115 is an integral membrane protein of the Golgi complex involved in retrograde transport. 24806965 0 35 theme membrane 23:30 arg1 TMEM115 0:6 TMEM115 0:6 TMEM115 0:6 TMEM115 is an integral membrane protein of the Golgi complex involved in retrograde transport. 24806965 5 36 theme COG 761:763 arg1 complex 766:772 the conserved oligomeric Golgi (COG) complex 729:772 the conserved oligomeric Golgi (COG) complex 729:772 Functionally, TMEM115 knockdown or overexpression delays Brefeldin-A-induced Golgi-to-ER retrograde transport, phenocopying cells with mutations or silencing of the conserved oligomeric Golgi (COG) complex. 24806965 2 37 from located 377:383 arg1 region 403:408 the N-terminal region 388:408 the N-terminal region 388:408 Biochemical and cell biological analysis suggested that TMEM115 has four candidate transmembrane domains located in the N-terminal region. 24806965 1 38 theme membrane 206:213 arg1 TMEM115 224:230 TMEM115 224:230 TMEM115 224:230 Searching and evaluating the Human Protein Atlas for transmembrane proteins enabled us to identify an integral membrane protein, TMEM115, that is enriched in the Golgi complex. 24806965 1 38 theme membrane 206:213 arg1 protein 215:221 an integral membrane protein 194:221 an integral membrane protein 194:221 Searching and evaluating the Human Protein Atlas for transmembrane proteins enabled us to identify an integral membrane protein, TMEM115, that is enriched in the Golgi complex. 24806965 8 39 theme O-linked 1238:1245 arg1 profile 1261:1267 an altered O-linked glycosylation profile 1227:1267 an altered O-linked glycosylation profile 1227:1267 Knockdown of TMEM115 also reduces the binding of the lectins peanut agglutinin (PNA) and Helix pomatia agglutinin (HPA), suggesting an altered O-linked glycosylation profile. 24806965 9 40 theme complex 1455:1461 arg1 machinery 1434:1442 the machinery 1430:1442 the machinery of the COG complex 1430:1461 These results establish that TMEM115 is an integral membrane protein of the Golgi stack regulating Golgi-to-ER retrograde transport and is likely to be part of the machinery of the COG complex. 24806965 7 41 theme Golgi 1078:1082 arg1 targeting 1084:1092 Golgi targeting 1078:1092 Golgi targeting 1078:1092 A short region (residues 206-229) immediately to the C-terminal side of the fourth transmembrane domain is both necessary and sufficient for Golgi targeting. 24806965 4 42 theme Golgi 551:555 arg1 cisternae 557:565 the Golgi cisternae 547:565 the Golgi cisternae 547:565 Immunofluorescence analysis supports that TMEM115 is enriched in the Golgi cisternae. 24806965 8 43 theme altered 1230:1236 arg1 profile 1261:1267 an altered O-linked glycosylation profile 1227:1267 an altered O-linked glycosylation profile 1227:1267 Knockdown of TMEM115 also reduces the binding of the lectins peanut agglutinin (PNA) and Helix pomatia agglutinin (HPA), suggesting an altered O-linked glycosylation profile. 24806965 6 44 theme in 802:803 arg1 experiments 819:829 in vitro binding experiments 802:829 in vitro binding experiments 802:829 Co-immunoprecipitation and in vitro binding experiments reveals that TMEM115 interacts with the COG complex, and might self-interact to form dimers or oligomers. 24806965 8 45 theme peanut 1156:1161 arg1 PNA 1175:1177 PNA 1175:1177 PNA 1175:1177 Knockdown of TMEM115 also reduces the binding of the lectins peanut agglutinin (PNA) and Helix pomatia agglutinin (HPA), suggesting an altered O-linked glycosylation profile. 24806965 8 45 theme peanut 1156:1161 arg1 agglutinin 1163:1172 peanut agglutinin 1156:1172 peanut agglutinin (PNA) 1156:1178 Knockdown of TMEM115 also reduces the binding of the lectins peanut agglutinin (PNA) and Helix pomatia agglutinin (HPA), suggesting an altered O-linked glycosylation profile. 24806965 8 45 theme peanut 1156:1161 arg1 lectins 1148:1154 the lectins peanut agglutinin (PNA) and Helix pomatia agglutinin (HPA) 1144:1213 the lectins peanut agglutinin (PNA) and Helix pomatia agglutinin (HPA) 1144:1213 Knockdown of TMEM115 also reduces the binding of the lectins peanut agglutinin (PNA) and Helix pomatia agglutinin (HPA), suggesting an altered O-linked glycosylation profile. 24806965 8 46 theme lectins 1148:1154 arg1 binding 1133:1139 the binding 1129:1139 the binding of the lectins peanut agglutinin (PNA) and Helix pomatia agglutinin (HPA) 1129:1213 Knockdown of TMEM115 also reduces the binding of the lectins peanut agglutinin (PNA) and Helix pomatia agglutinin (HPA), suggesting an altered O-linked glycosylation profile. 24806965 5 47 theme conserved 733:741 arg1 complex 766:772 the conserved oligomeric Golgi (COG) complex 729:772 the conserved oligomeric Golgi (COG) complex 729:772 Functionally, TMEM115 knockdown or overexpression delays Brefeldin-A-induced Golgi-to-ER retrograde transport, phenocopying cells with mutations or silencing of the conserved oligomeric Golgi (COG) complex. 24806965 9 48 theme machinery 1434:1442 arg1 part 1422:1425 part 1422:1425 part of the machinery of the COG complex 1422:1461 These results establish that TMEM115 is an integral membrane protein of the Golgi stack regulating Golgi-to-ER retrograde transport and is likely to be part of the machinery of the COG complex. 24806965 6 49 theme binding 811:817 arg1 experiments 819:829 in vitro binding experiments 802:829 in vitro binding experiments 802:829 Co-immunoprecipitation and in vitro binding experiments reveals that TMEM115 interacts with the COG complex, and might self-interact to form dimers or oligomers. 24806965 2 50 from region 403:408 arg1 located 377:383 located 377:383 located 377:383 Biochemical and cell biological analysis suggested that TMEM115 has four candidate transmembrane domains located in the N-terminal region. 24806965 1 51 theme Human 124:128 arg1 Atlas 138:142 the Human Protein Atlas 120:142 the Human Protein Atlas for transmembrane proteins 120:169 Searching and evaluating the Human Protein Atlas for transmembrane proteins enabled us to identify an integral membrane protein, TMEM115, that is enriched in the Golgi complex. 24806965 7 52 theme short 939:943 arg1 region 945:950 A short region 937:950 A short region (residues 206-229) immediately to the C-terminal side of the fourth transmembrane domain 937:1039 A short region (residues 206-229) immediately to the C-terminal side of the fourth transmembrane domain is both necessary and sufficient for Golgi targeting. 24806965 7 52 theme short 939:943 arg1 necessary 1049:1057 necessary 1049:1057 necessary 1049:1057 A short region (residues 206-229) immediately to the C-terminal side of the fourth transmembrane domain is both necessary and sufficient for Golgi targeting. 24806965 7 52 theme short 939:943 arg1 residues 953:960 residues 206-229 953:968 residues 206-229 953:968 A short region (residues 206-229) immediately to the C-terminal side of the fourth transmembrane domain is both necessary and sufficient for Golgi targeting. 24806965 0 53 theme complex 53:59 arg1 protein 32:38 an integral membrane protein 11:38 an integral membrane protein of the Golgi complex involved in retrograde transport 11:92 TMEM115 is an integral membrane protein of the Golgi complex involved in retrograde transport. 24806965 0 53 theme complex 53:59 arg1 TMEM115 0:6 TMEM115 0:6 TMEM115 0:6 TMEM115 is an integral membrane protein of the Golgi complex involved in retrograde transport. 24806965 2 54 theme N-terminal 392:401 arg1 region 403:408 the N-terminal region 388:408 the N-terminal region 388:408 Biochemical and cell biological analysis suggested that TMEM115 has four candidate transmembrane domains located in the N-terminal region. 24806965 7 55 theme domain 1034:1039 arg1 side 1001:1004 the C-terminal side 986:1004 the C-terminal side of the fourth transmembrane domain 986:1039 A short region (residues 206-229) immediately to the C-terminal side of the fourth transmembrane domain is both necessary and sufficient for Golgi targeting. 24806965 2 56 theme transmembrane 355:367 arg1 domains 369:375 four candidate transmembrane domains 340:375 four candidate transmembrane domains located in the N-terminal region 340:408 Biochemical and cell biological analysis suggested that TMEM115 has four candidate transmembrane domains located in the N-terminal region. 24806965 8 57 theme glycosylation 1247:1259 arg1 profile 1261:1267 an altered O-linked glycosylation profile 1227:1267 an altered O-linked glycosylation profile 1227:1267 Knockdown of TMEM115 also reduces the binding of the lectins peanut agglutinin (PNA) and Helix pomatia agglutinin (HPA), suggesting an altered O-linked glycosylation profile. 24806965 0 58 theme Golgi 47:51 arg1 complex 53:59 the Golgi complex 43:59 the Golgi complex involved in retrograde transport 43:92 TMEM115 is an integral membrane protein of the Golgi complex involved in retrograde transport. 24806965 2 59 theme candidate 345:353 arg1 domains 369:375 four candidate transmembrane domains 340:375 four candidate transmembrane domains located in the N-terminal region 340:408 Biochemical and cell biological analysis suggested that TMEM115 has four candidate transmembrane domains located in the N-terminal region. 24806965 6 60 dep in 802:803 arg1 vitro 805:809 vitro 805:809 vitro 805:809 Co-immunoprecipitation and in vitro binding experiments reveals that TMEM115 interacts with the COG complex, and might self-interact to form dimers or oligomers. 24806965 5 61 theme complex 766:772 arg1 silencing 716:724 silencing 716:724 silencing of the conserved oligomeric Golgi (COG) complex 716:772 Functionally, TMEM115 knockdown or overexpression delays Brefeldin-A-induced Golgi-to-ER retrograde transport, phenocopying cells with mutations or silencing of the conserved oligomeric Golgi (COG) complex. 24806965 5 61 theme complex 766:772 arg1 mutations 703:711 mutations 703:711 mutations 703:711 Functionally, TMEM115 knockdown or overexpression delays Brefeldin-A-induced Golgi-to-ER retrograde transport, phenocopying cells with mutations or silencing of the conserved oligomeric Golgi (COG) complex. 25270010 7 0 theme populations 1549:1559 arg1 existence 1523:1531 existence 1523:1531 existence of two distinct populations of endothelial cell in UIP 1523:1586 CONCLUSION These results may indicate existence of two distinct populations of endothelial cell in UIP with markedly different patterns of glycosylation, reflecting a pattern of differentiation and angiogenesis, which is not detectable morphologically. 25270010 4 1 link N-linked 775:782 arg1 sequences 784:792 small complex and bi/tri-antennary bisected complex N-linked sequences 723:792 small complex and bi/tri-antennary bisected complex N-linked sequences bolund by Concanavalin A and erythro-phytohemagglutinin 723:848 RESULTS High expression of several classes of glycan was seen de novo in capillary endothelial cells from patients with UIP including small complex and bi/tri-antennary bisected complex N-linked sequences bolund by Concanavalin A and erythro-phytohemagglutinin, respectively, GalNAca1 residues bound by Helix pomatia and Maclura pomifera agglutinins, and L-fucosylated derivatives of type II glycan chains recognized by Ulex europaeus agglutinin-I. 25270010 6 2 theme glycan 1346:1351 arg1 chains 1353:1358 type I glycan chains 1339:1358 type I glycan chains 1339:1358 In contrast, L-fucosylated derivatives of type I glycan chains were absent in cells from cases of UIP when Anguilla anguilla agglutinin was applied, unlike the situation in normal tissue. 25270010 5 3 theme endothelial 1271:1281 arg1 cells 1283:1287 the capillary endothelial cells 1257:1287 the capillary endothelial cells of UIP 1257:1294 Glycans bound by agglutinins from Lycopersicon esculentum (β1,4GlcNAc) and Wisteria floribunda (GalNAc) as well as GlcNAc oligomers bound by Phytolacca americana and succinylated Wheat Germ agglutinin were also seen in the capillary endothelial cells of UIP. 25270010 4 4 theme classes 624:630 arg1 expression 602:611 High expression 597:611 High expression of several classes of glycan 597:640 RESULTS High expression of several classes of glycan was seen de novo in capillary endothelial cells from patients with UIP including small complex and bi/tri-antennary bisected complex N-linked sequences bolund by Concanavalin A and erythro-phytohemagglutinin, respectively, GalNAca1 residues bound by Helix pomatia and Maclura pomifera agglutinins, and L-fucosylated derivatives of type II glycan chains recognized by Ulex europaeus agglutinin-I. 25270010 6 5 theme type 1339:1342 arg1 chains 1353:1358 type I glycan chains 1339:1358 type I glycan chains 1339:1358 In contrast, L-fucosylated derivatives of type I glycan chains were absent in cells from cases of UIP when Anguilla anguilla agglutinin was applied, unlike the situation in normal tissue. 25270010 3 6 theme revealing 571:579 arg1 system 581:586 an avidin-peroxidase revealing system 550:586 an avidin-peroxidase revealing system 550:586 METHODS Sections of formalin-fixed, paraffin-embedded blocks from 16 cases of UIP were studied by lectin histochemistry with a panel of 27 biotinylated lectins and an avidin-peroxidase revealing system. 25270010 4 7 from patients 695:702 arg1 cells 684:688 capillary endothelial cells 662:688 capillary endothelial cells from patients with UIP including small complex and bi/tri-antennary bisected complex N-linked sequences bolund by Concanavalin A and erythro-phytohemagglutinin 662:848 RESULTS High expression of several classes of glycan was seen de novo in capillary endothelial cells from patients with UIP including small complex and bi/tri-antennary bisected complex N-linked sequences bolund by Concanavalin A and erythro-phytohemagglutinin, respectively, GalNAca1 residues bound by Helix pomatia and Maclura pomifera agglutinins, and L-fucosylated derivatives of type II glycan chains recognized by Ulex europaeus agglutinin-I. 25270010 2 8 theme cells 300:304 arg1 glycotypes 264:273 the glycotypes 260:273 the glycotypes of capillary endothelial cells in usual interstitial pneumonia (UIP) 260:342 OBJECTIVE To identify and specify the glycotypes of capillary endothelial cells in usual interstitial pneumonia (UIP) compared to those found in normal tissue. 25270010 4 9 theme Maclura 910:916 arg1 agglutinins 927:937 Maclura pomifera agglutinins 910:937 Maclura pomifera agglutinins 910:937 RESULTS High expression of several classes of glycan was seen de novo in capillary endothelial cells from patients with UIP including small complex and bi/tri-antennary bisected complex N-linked sequences bolund by Concanavalin A and erythro-phytohemagglutinin, respectively, GalNAca1 residues bound by Helix pomatia and Maclura pomifera agglutinins, and L-fucosylated derivatives of type II glycan chains recognized by Ulex europaeus agglutinin-I. 25270010 4 10 theme glycan 981:986 arg1 chains 988:993 type II glycan chains 973:993 type II glycan chains 973:993 RESULTS High expression of several classes of glycan was seen de novo in capillary endothelial cells from patients with UIP including small complex and bi/tri-antennary bisected complex N-linked sequences bolund by Concanavalin A and erythro-phytohemagglutinin, respectively, GalNAca1 residues bound by Helix pomatia and Maclura pomifera agglutinins, and L-fucosylated derivatives of type II glycan chains recognized by Ulex europaeus agglutinin-I. 25270010 5 11 dep Lycopersicon 1072:1083 arg1 esculentum 1085:1094 Lycopersicon esculentum 1072:1094 Lycopersicon esculentum (β1,4GlcNAc) 1072:1107 Glycans bound by agglutinins from Lycopersicon esculentum (β1,4GlcNAc) and Wisteria floribunda (GalNAc) as well as GlcNAc oligomers bound by Phytolacca americana and succinylated Wheat Germ agglutinin were also seen in the capillary endothelial cells of UIP. 25270010 4 12 theme complex 729:735 arg1 sequences 784:792 small complex and bi/tri-antennary bisected complex N-linked sequences 723:792 small complex and bi/tri-antennary bisected complex N-linked sequences bolund by Concanavalin A and erythro-phytohemagglutinin 723:848 RESULTS High expression of several classes of glycan was seen de novo in capillary endothelial cells from patients with UIP including small complex and bi/tri-antennary bisected complex N-linked sequences bolund by Concanavalin A and erythro-phytohemagglutinin, respectively, GalNAca1 residues bound by Helix pomatia and Maclura pomifera agglutinins, and L-fucosylated derivatives of type II glycan chains recognized by Ulex europaeus agglutinin-I. 25270010 4 13 theme capillary 662:670 arg1 cells 684:688 capillary endothelial cells 662:688 capillary endothelial cells from patients with UIP including small complex and bi/tri-antennary bisected complex N-linked sequences bolund by Concanavalin A and erythro-phytohemagglutinin 662:848 RESULTS High expression of several classes of glycan was seen de novo in capillary endothelial cells from patients with UIP including small complex and bi/tri-antennary bisected complex N-linked sequences bolund by Concanavalin A and erythro-phytohemagglutinin, respectively, GalNAca1 residues bound by Helix pomatia and Maclura pomifera agglutinins, and L-fucosylated derivatives of type II glycan chains recognized by Ulex europaeus agglutinin-I. 25270010 6 14 from situation 1457:1465 arg1 tissue 1477:1482 normal tissue 1470:1482 normal tissue 1470:1482 In contrast, L-fucosylated derivatives of type I glycan chains were absent in cells from cases of UIP when Anguilla anguilla agglutinin was applied, unlike the situation in normal tissue. 25270010 1 15 theme fibrosing 138:146 arg1 alveolitis 148:157 cryptogenic fibrosing alveolitis 126:157 cryptogenic fibrosing alveolitis 126:157 BACKGROUND The pathological classification of cryptogenic fibrosing alveolitis has been a matter of debate and controversy for histopathologists. 25270010 5 16 from Lycopersicon 1072:1083 arg1 agglutinins 1055:1065 agglutinins 1055:1065 agglutinins from Lycopersicon esculentum (β1,4GlcNAc) and Wisteria floribunda (GalNAc) as well as GlcNAc oligomers bound by Phytolacca americana and succinylated Wheat Germ agglutinin 1055:1237 Glycans bound by agglutinins from Lycopersicon esculentum (β1,4GlcNAc) and Wisteria floribunda (GalNAc) as well as GlcNAc oligomers bound by Phytolacca americana and succinylated Wheat Germ agglutinin were also seen in the capillary endothelial cells of UIP. 25270010 5 16 from Lycopersicon 1072:1083 arg1 GalNAc 1134:1139 GalNAc 1134:1139 GalNAc 1134:1139 Glycans bound by agglutinins from Lycopersicon esculentum (β1,4GlcNAc) and Wisteria floribunda (GalNAc) as well as GlcNAc oligomers bound by Phytolacca americana and succinylated Wheat Germ agglutinin were also seen in the capillary endothelial cells of UIP. 25270010 5 16 from Lycopersicon 1072:1083 arg1 oligomers 1160:1168 GlcNAc oligomers 1153:1168 agglutinins from Lycopersicon esculentum (β1,4GlcNAc) and Wisteria floribunda (GalNAc) as well as GlcNAc oligomers bound by Phytolacca americana and succinylated Wheat Germ agglutinin 1055:1237 Glycans bound by agglutinins from Lycopersicon esculentum (β1,4GlcNAc) and Wisteria floribunda (GalNAc) as well as GlcNAc oligomers bound by Phytolacca americana and succinylated Wheat Germ agglutinin were also seen in the capillary endothelial cells of UIP. 25270010 4 17 theme type 973:976 arg1 chains 988:993 type II glycan chains 973:993 type II glycan chains 973:993 RESULTS High expression of several classes of glycan was seen de novo in capillary endothelial cells from patients with UIP including small complex and bi/tri-antennary bisected complex N-linked sequences bolund by Concanavalin A and erythro-phytohemagglutinin, respectively, GalNAca1 residues bound by Helix pomatia and Maclura pomifera agglutinins, and L-fucosylated derivatives of type II glycan chains recognized by Ulex europaeus agglutinin-I. 25270010 4 18 theme bisected 758:765 arg1 complex 767:773 bi/tri-antennary bisected complex 741:773 bi/tri-antennary bisected complex 741:773 RESULTS High expression of several classes of glycan was seen de novo in capillary endothelial cells from patients with UIP including small complex and bi/tri-antennary bisected complex N-linked sequences bolund by Concanavalin A and erythro-phytohemagglutinin, respectively, GalNAca1 residues bound by Helix pomatia and Maclura pomifera agglutinins, and L-fucosylated derivatives of type II glycan chains recognized by Ulex europaeus agglutinin-I. 25270010 2 19 theme capillary 278:286 arg1 cells 300:304 capillary endothelial cells 278:304 capillary endothelial cells in usual interstitial pneumonia (UIP) 278:342 OBJECTIVE To identify and specify the glycotypes of capillary endothelial cells in usual interstitial pneumonia (UIP) compared to those found in normal tissue. 25270010 6 20 gly L-fucosylated 1310:1322 arg1 derivatives 1324:1334 L-fucosylated derivatives 1310:1334 L-fucosylated derivatives of type I glycan chains 1310:1358 In contrast, L-fucosylated derivatives of type I glycan chains were absent in cells from cases of UIP when Anguilla anguilla agglutinin was applied, unlike the situation in normal tissue. 25270010 7 21 dep CONCLUSION 1485:1494 arg1 indicate 1514:1521 indicate 1514:1521 indicate 1514:1521 CONCLUSION These results may indicate existence of two distinct populations of endothelial cell in UIP with markedly different patterns of glycosylation, reflecting a pattern of differentiation and angiogenesis, which is not detectable morphologically. 25270010 3 22 theme avidin-peroxidase 553:569 arg1 system 581:586 an avidin-peroxidase revealing system 550:586 an avidin-peroxidase revealing system 550:586 METHODS Sections of formalin-fixed, paraffin-embedded blocks from 16 cases of UIP were studied by lectin histochemistry with a panel of 27 biotinylated lectins and an avidin-peroxidase revealing system. 25270010 0 23 theme interstitial 56:67 arg1 pneumonia 69:77 usual interstitial pneumonia 50:77 usual interstitial pneumonia 50:77 The glycoprofile patterns of endothelial cells in usual interstitial pneumonia. 25270010 5 24 theme Phytolacca 1179:1188 arg1 americana 1190:1198 Phytolacca americana 1179:1198 Phytolacca americana 1179:1198 Glycans bound by agglutinins from Lycopersicon esculentum (β1,4GlcNAc) and Wisteria floribunda (GalNAc) as well as GlcNAc oligomers bound by Phytolacca americana and succinylated Wheat Germ agglutinin were also seen in the capillary endothelial cells of UIP. 25270010 0 25 from patterns 17:24 arg1 pneumonia 69:77 usual interstitial pneumonia 50:77 usual interstitial pneumonia 50:77 The glycoprofile patterns of endothelial cells in usual interstitial pneumonia. 25270010 4 26 theme small 723:727 arg1 complex 729:735 small complex 723:735 small complex 723:735 RESULTS High expression of several classes of glycan was seen de novo in capillary endothelial cells from patients with UIP including small complex and bi/tri-antennary bisected complex N-linked sequences bolund by Concanavalin A and erythro-phytohemagglutinin, respectively, GalNAca1 residues bound by Helix pomatia and Maclura pomifera agglutinins, and L-fucosylated derivatives of type II glycan chains recognized by Ulex europaeus agglutinin-I. 25270010 5 27 from floribunda 1122:1131 arg1 agglutinins 1055:1065 agglutinins 1055:1065 agglutinins from Lycopersicon esculentum (β1,4GlcNAc) and Wisteria floribunda (GalNAc) as well as GlcNAc oligomers bound by Phytolacca americana and succinylated Wheat Germ agglutinin 1055:1237 Glycans bound by agglutinins from Lycopersicon esculentum (β1,4GlcNAc) and Wisteria floribunda (GalNAc) as well as GlcNAc oligomers bound by Phytolacca americana and succinylated Wheat Germ agglutinin were also seen in the capillary endothelial cells of UIP. 25270010 5 27 from floribunda 1122:1131 arg1 GalNAc 1134:1139 GalNAc 1134:1139 GalNAc 1134:1139 Glycans bound by agglutinins from Lycopersicon esculentum (β1,4GlcNAc) and Wisteria floribunda (GalNAc) as well as GlcNAc oligomers bound by Phytolacca americana and succinylated Wheat Germ agglutinin were also seen in the capillary endothelial cells of UIP. 25270010 5 27 from floribunda 1122:1131 arg1 oligomers 1160:1168 GlcNAc oligomers 1153:1168 agglutinins from Lycopersicon esculentum (β1,4GlcNAc) and Wisteria floribunda (GalNAc) as well as GlcNAc oligomers bound by Phytolacca americana and succinylated Wheat Germ agglutinin 1055:1237 Glycans bound by agglutinins from Lycopersicon esculentum (β1,4GlcNAc) and Wisteria floribunda (GalNAc) as well as GlcNAc oligomers bound by Phytolacca americana and succinylated Wheat Germ agglutinin were also seen in the capillary endothelial cells of UIP. 25270010 4 28 theme Ulex 1009:1012 arg1 europaeus 1014:1022 Ulex europaeus 1009:1022 Ulex europaeus agglutinin-I 1009:1035 RESULTS High expression of several classes of glycan was seen de novo in capillary endothelial cells from patients with UIP including small complex and bi/tri-antennary bisected complex N-linked sequences bolund by Concanavalin A and erythro-phytohemagglutinin, respectively, GalNAca1 residues bound by Helix pomatia and Maclura pomifera agglutinins, and L-fucosylated derivatives of type II glycan chains recognized by Ulex europaeus agglutinin-I. 25270010 4 29 theme Concanavalin 804:815 arg1 A 817:817 Concanavalin A 804:817 Concanavalin A 804:817 RESULTS High expression of several classes of glycan was seen de novo in capillary endothelial cells from patients with UIP including small complex and bi/tri-antennary bisected complex N-linked sequences bolund by Concanavalin A and erythro-phytohemagglutinin, respectively, GalNAca1 residues bound by Helix pomatia and Maclura pomifera agglutinins, and L-fucosylated derivatives of type II glycan chains recognized by Ulex europaeus agglutinin-I. 25270010 6 30 theme anguilla 1413:1420 arg1 agglutinin 1422:1431 Anguilla anguilla agglutinin 1404:1431 Anguilla anguilla agglutinin 1404:1431 In contrast, L-fucosylated derivatives of type I glycan chains were absent in cells from cases of UIP when Anguilla anguilla agglutinin was applied, unlike the situation in normal tissue. 25270010 5 31 theme GlcNAc 1153:1158 arg1 oligomers 1160:1168 GlcNAc oligomers 1153:1168 agglutinins from Lycopersicon esculentum (β1,4GlcNAc) and Wisteria floribunda (GalNAc) as well as GlcNAc oligomers bound by Phytolacca americana and succinylated Wheat Germ agglutinin 1055:1237 Glycans bound by agglutinins from Lycopersicon esculentum (β1,4GlcNAc) and Wisteria floribunda (GalNAc) as well as GlcNAc oligomers bound by Phytolacca americana and succinylated Wheat Germ agglutinin were also seen in the capillary endothelial cells of UIP. 25270010 2 32 theme usual 309:313 arg1 UIP 339:341 UIP 339:341 UIP 339:341 OBJECTIVE To identify and specify the glycotypes of capillary endothelial cells in usual interstitial pneumonia (UIP) compared to those found in normal tissue. 25270010 2 32 theme usual 309:313 arg1 pneumonia 328:336 usual interstitial pneumonia 309:336 usual interstitial pneumonia (UIP) 309:342 OBJECTIVE To identify and specify the glycotypes of capillary endothelial cells in usual interstitial pneumonia (UIP) compared to those found in normal tissue. 25270010 2 33 located found 362:366 arg1 tissue 378:383 normal tissue 371:383 normal tissue 371:383 OBJECTIVE To identify and specify the glycotypes of capillary endothelial cells in usual interstitial pneumonia (UIP) compared to those found in normal tissue. 25270010 2 33 located found 362:366 arg2 those 356:360 those 356:360 those 356:360 OBJECTIVE To identify and specify the glycotypes of capillary endothelial cells in usual interstitial pneumonia (UIP) compared to those found in normal tissue. 25270010 6 34 theme normal 1470:1475 arg1 tissue 1477:1482 normal tissue 1470:1482 normal tissue 1470:1482 In contrast, L-fucosylated derivatives of type I glycan chains were absent in cells from cases of UIP when Anguilla anguilla agglutinin was applied, unlike the situation in normal tissue. 25270010 4 35 theme N-linked 775:782 arg1 sequences 784:792 small complex and bi/tri-antennary bisected complex N-linked sequences 723:792 small complex and bi/tri-antennary bisected complex N-linked sequences bolund by Concanavalin A and erythro-phytohemagglutinin 723:848 RESULTS High expression of several classes of glycan was seen de novo in capillary endothelial cells from patients with UIP including small complex and bi/tri-antennary bisected complex N-linked sequences bolund by Concanavalin A and erythro-phytohemagglutinin, respectively, GalNAca1 residues bound by Helix pomatia and Maclura pomifera agglutinins, and L-fucosylated derivatives of type II glycan chains recognized by Ulex europaeus agglutinin-I. 25270010 6 36 from cases 1386:1390 arg1 cells 1375:1379 cells 1375:1379 cells from cases of UIP 1375:1397 In contrast, L-fucosylated derivatives of type I glycan chains were absent in cells from cases of UIP when Anguilla anguilla agglutinin was applied, unlike the situation in normal tissue. 25270010 1 37 theme pathological 95:106 arg1 matter 170:175 a matter 168:175 a matter of debate and controversy for histopathologists 168:223 BACKGROUND The pathological classification of cryptogenic fibrosing alveolitis has been a matter of debate and controversy for histopathologists. 25270010 1 37 theme pathological 95:106 arg1 classification 108:121 The pathological classification 91:121 The pathological classification of cryptogenic fibrosing alveolitis 91:157 BACKGROUND The pathological classification of cryptogenic fibrosing alveolitis has been a matter of debate and controversy for histopathologists. 25270010 3 38 theme METHODS 386:392 arg1 Sections 394:401 METHODS Sections 386:401 METHODS Sections of formalin-fixed, paraffin-embedded blocks from 16 cases of UIP 386:466 METHODS Sections of formalin-fixed, paraffin-embedded blocks from 16 cases of UIP were studied by lectin histochemistry with a panel of 27 biotinylated lectins and an avidin-peroxidase revealing system. 25270010 4 39 theme bolund 794:799 arg1 sequences 784:792 small complex and bi/tri-antennary bisected complex N-linked sequences 723:792 small complex and bi/tri-antennary bisected complex N-linked sequences bolund by Concanavalin A and erythro-phytohemagglutinin 723:848 RESULTS High expression of several classes of glycan was seen de novo in capillary endothelial cells from patients with UIP including small complex and bi/tri-antennary bisected complex N-linked sequences bolund by Concanavalin A and erythro-phytohemagglutinin, respectively, GalNAca1 residues bound by Helix pomatia and Maclura pomifera agglutinins, and L-fucosylated derivatives of type II glycan chains recognized by Ulex europaeus agglutinin-I. 25270010 3 40 theme blocks 440:445 arg1 Sections 394:401 METHODS Sections 386:401 METHODS Sections of formalin-fixed, paraffin-embedded blocks from 16 cases of UIP 386:466 METHODS Sections of formalin-fixed, paraffin-embedded blocks from 16 cases of UIP were studied by lectin histochemistry with a panel of 27 biotinylated lectins and an avidin-peroxidase revealing system. 25270010 0 41 theme endothelial 29:39 arg1 cells 41:45 endothelial cells 29:45 endothelial cells 29:45 The glycoprofile patterns of endothelial cells in usual interstitial pneumonia. 25270010 5 42 theme Wheat 1217:1221 arg1 agglutinin 1228:1237 succinylated Wheat Germ agglutinin 1204:1237 succinylated Wheat Germ agglutinin 1204:1237 Glycans bound by agglutinins from Lycopersicon esculentum (β1,4GlcNAc) and Wisteria floribunda (GalNAc) as well as GlcNAc oligomers bound by Phytolacca americana and succinylated Wheat Germ agglutinin were also seen in the capillary endothelial cells of UIP. 25270010 6 43 from absent 1365:1370 arg1 cells 1375:1379 cells 1375:1379 cells from cases of UIP 1375:1397 In contrast, L-fucosylated derivatives of type I glycan chains were absent in cells from cases of UIP when Anguilla anguilla agglutinin was applied, unlike the situation in normal tissue. 25270010 6 43 from absent 1365:1370 arg1 contrast 1300:1307 contrast 1300:1307 contrast 1300:1307 In contrast, L-fucosylated derivatives of type I glycan chains were absent in cells from cases of UIP when Anguilla anguilla agglutinin was applied, unlike the situation in normal tissue. 25270010 6 44 from cells 1375:1379 arg1 absent 1365:1370 absent 1365:1370 absent 1365:1370 In contrast, L-fucosylated derivatives of type I glycan chains were absent in cells from cases of UIP when Anguilla anguilla agglutinin was applied, unlike the situation in normal tissue. 25270010 7 45 theme cell 1576:1579 arg1 populations 1549:1559 two distinct populations 1536:1559 two distinct populations of endothelial cell 1536:1579 CONCLUSION These results may indicate existence of two distinct populations of endothelial cell in UIP with markedly different patterns of glycosylation, reflecting a pattern of differentiation and angiogenesis, which is not detectable morphologically. 25270010 5 46 theme UIP 1292:1294 arg1 cells 1283:1287 the capillary endothelial cells 1257:1287 the capillary endothelial cells of UIP 1257:1294 Glycans bound by agglutinins from Lycopersicon esculentum (β1,4GlcNAc) and Wisteria floribunda (GalNAc) as well as GlcNAc oligomers bound by Phytolacca americana and succinylated Wheat Germ agglutinin were also seen in the capillary endothelial cells of UIP. 25270010 3 47 from cases 455:459 arg1 blocks 440:445 formalin-fixed, paraffin-embedded blocks 406:445 formalin-fixed, paraffin-embedded blocks from 16 cases of UIP 406:466 METHODS Sections of formalin-fixed, paraffin-embedded blocks from 16 cases of UIP were studied by lectin histochemistry with a panel of 27 biotinylated lectins and an avidin-peroxidase revealing system. 25270010 3 47 from cases 455:459 arg1 Sections 394:401 METHODS Sections 386:401 METHODS Sections of formalin-fixed, paraffin-embedded blocks from 16 cases of UIP 386:466 METHODS Sections of formalin-fixed, paraffin-embedded blocks from 16 cases of UIP were studied by lectin histochemistry with a panel of 27 biotinylated lectins and an avidin-peroxidase revealing system. 25270010 3 48 theme biotinylated 525:536 arg1 lectins 538:544 27 biotinylated lectins 522:544 27 biotinylated lectins 522:544 METHODS Sections of formalin-fixed, paraffin-embedded blocks from 16 cases of UIP were studied by lectin histochemistry with a panel of 27 biotinylated lectins and an avidin-peroxidase revealing system. 25270010 7 49 theme distinct 1540:1547 arg1 populations 1549:1559 two distinct populations 1536:1559 two distinct populations of endothelial cell 1536:1579 CONCLUSION These results may indicate existence of two distinct populations of endothelial cell in UIP with markedly different patterns of glycosylation, reflecting a pattern of differentiation and angiogenesis, which is not detectable morphologically. 25270010 2 50 dep OBJECTIVE 226:234 arg1 specify 252:258 specify 252:258 specify the glycotypes of capillary endothelial cells in usual interstitial pneumonia (UIP) 252:342 OBJECTIVE To identify and specify the glycotypes of capillary endothelial cells in usual interstitial pneumonia (UIP) compared to those found in normal tissue. 25270010 2 50 dep OBJECTIVE 226:234 arg1 identify 239:246 identify 239:246 identify 239:246 OBJECTIVE To identify and specify the glycotypes of capillary endothelial cells in usual interstitial pneumonia (UIP) compared to those found in normal tissue. 25270010 6 51 theme chains 1353:1358 arg1 derivatives 1324:1334 L-fucosylated derivatives 1310:1334 L-fucosylated derivatives of type I glycan chains 1310:1358 In contrast, L-fucosylated derivatives of type I glycan chains were absent in cells from cases of UIP when Anguilla anguilla agglutinin was applied, unlike the situation in normal tissue. 25270010 2 52 theme normal 371:376 arg1 tissue 378:383 normal tissue 371:383 normal tissue 371:383 OBJECTIVE To identify and specify the glycotypes of capillary endothelial cells in usual interstitial pneumonia (UIP) compared to those found in normal tissue. 25270010 5 53 theme capillary 1261:1269 arg1 cells 1283:1287 the capillary endothelial cells 1257:1287 the capillary endothelial cells of UIP 1257:1294 Glycans bound by agglutinins from Lycopersicon esculentum (β1,4GlcNAc) and Wisteria floribunda (GalNAc) as well as GlcNAc oligomers bound by Phytolacca americana and succinylated Wheat Germ agglutinin were also seen in the capillary endothelial cells of UIP. 25270010 4 54 theme pomifera 918:925 arg1 agglutinins 927:937 Maclura pomifera agglutinins 910:937 Maclura pomifera agglutinins 910:937 RESULTS High expression of several classes of glycan was seen de novo in capillary endothelial cells from patients with UIP including small complex and bi/tri-antennary bisected complex N-linked sequences bolund by Concanavalin A and erythro-phytohemagglutinin, respectively, GalNAca1 residues bound by Helix pomatia and Maclura pomifera agglutinins, and L-fucosylated derivatives of type II glycan chains recognized by Ulex europaeus agglutinin-I. 25270010 6 55 theme I 1344:1344 arg1 chains 1353:1358 type I glycan chains 1339:1358 type I glycan chains 1339:1358 In contrast, L-fucosylated derivatives of type I glycan chains were absent in cells from cases of UIP when Anguilla anguilla agglutinin was applied, unlike the situation in normal tissue. 25270010 2 56 theme interstitial 315:326 arg1 UIP 339:341 UIP 339:341 UIP 339:341 OBJECTIVE To identify and specify the glycotypes of capillary endothelial cells in usual interstitial pneumonia (UIP) compared to those found in normal tissue. 25270010 2 56 theme interstitial 315:326 arg1 pneumonia 328:336 usual interstitial pneumonia 309:336 usual interstitial pneumonia (UIP) 309:342 OBJECTIVE To identify and specify the glycotypes of capillary endothelial cells in usual interstitial pneumonia (UIP) compared to those found in normal tissue. 25270010 4 57 theme several 616:622 arg1 classes 624:630 several classes 616:630 several classes of glycan 616:640 RESULTS High expression of several classes of glycan was seen de novo in capillary endothelial cells from patients with UIP including small complex and bi/tri-antennary bisected complex N-linked sequences bolund by Concanavalin A and erythro-phytohemagglutinin, respectively, GalNAca1 residues bound by Helix pomatia and Maclura pomifera agglutinins, and L-fucosylated derivatives of type II glycan chains recognized by Ulex europaeus agglutinin-I. 25270010 3 58 with histochemistry 491:504 arg1 panel 513:517 a panel 511:517 a panel of 27 biotinylated lectins 511:544 METHODS Sections of formalin-fixed, paraffin-embedded blocks from 16 cases of UIP were studied by lectin histochemistry with a panel of 27 biotinylated lectins and an avidin-peroxidase revealing system. 25270010 3 58 with histochemistry 491:504 arg1 system 581:586 an avidin-peroxidase revealing system 550:586 an avidin-peroxidase revealing system 550:586 METHODS Sections of formalin-fixed, paraffin-embedded blocks from 16 cases of UIP were studied by lectin histochemistry with a panel of 27 biotinylated lectins and an avidin-peroxidase revealing system. 25270010 1 59 theme debate 180:185 arg1 classification 108:121 The pathological classification 91:121 The pathological classification of cryptogenic fibrosing alveolitis 91:157 BACKGROUND The pathological classification of cryptogenic fibrosing alveolitis has been a matter of debate and controversy for histopathologists. 25270010 1 59 theme debate 180:185 arg1 matter 170:175 a matter 168:175 a matter of debate and controversy for histopathologists 168:223 BACKGROUND The pathological classification of cryptogenic fibrosing alveolitis has been a matter of debate and controversy for histopathologists. 25270010 4 60 theme Helix 892:896 arg1 pomatia 898:904 Helix pomatia 892:904 Helix pomatia 892:904 RESULTS High expression of several classes of glycan was seen de novo in capillary endothelial cells from patients with UIP including small complex and bi/tri-antennary bisected complex N-linked sequences bolund by Concanavalin A and erythro-phytohemagglutinin, respectively, GalNAca1 residues bound by Helix pomatia and Maclura pomifera agglutinins, and L-fucosylated derivatives of type II glycan chains recognized by Ulex europaeus agglutinin-I. 25270010 4 61 theme endothelial 672:682 arg1 cells 684:688 capillary endothelial cells 662:688 capillary endothelial cells from patients with UIP including small complex and bi/tri-antennary bisected complex N-linked sequences bolund by Concanavalin A and erythro-phytohemagglutinin 662:848 RESULTS High expression of several classes of glycan was seen de novo in capillary endothelial cells from patients with UIP including small complex and bi/tri-antennary bisected complex N-linked sequences bolund by Concanavalin A and erythro-phytohemagglutinin, respectively, GalNAca1 residues bound by Helix pomatia and Maclura pomifera agglutinins, and L-fucosylated derivatives of type II glycan chains recognized by Ulex europaeus agglutinin-I. 25270010 6 62 theme L-fucosylated 1310:1322 arg1 derivatives 1324:1334 L-fucosylated derivatives 1310:1334 L-fucosylated derivatives of type I glycan chains 1310:1358 In contrast, L-fucosylated derivatives of type I glycan chains were absent in cells from cases of UIP when Anguilla anguilla agglutinin was applied, unlike the situation in normal tissue. 25270010 1 63 theme controversy 191:201 arg1 classification 108:121 The pathological classification 91:121 The pathological classification of cryptogenic fibrosing alveolitis 91:157 BACKGROUND The pathological classification of cryptogenic fibrosing alveolitis has been a matter of debate and controversy for histopathologists. 25270010 1 63 theme controversy 191:201 arg1 matter 170:175 a matter 168:175 a matter of debate and controversy for histopathologists 168:223 BACKGROUND The pathological classification of cryptogenic fibrosing alveolitis has been a matter of debate and controversy for histopathologists. 25270010 6 64 theme UIP 1395:1397 arg1 cases 1386:1390 cases 1386:1390 cases of UIP 1386:1397 In contrast, L-fucosylated derivatives of type I glycan chains were absent in cells from cases of UIP when Anguilla anguilla agglutinin was applied, unlike the situation in normal tissue. 25270010 7 65 from existence 1523:1531 arg1 UIP 1584:1586 UIP 1584:1586 UIP 1584:1586 CONCLUSION These results may indicate existence of two distinct populations of endothelial cell in UIP with markedly different patterns of glycosylation, reflecting a pattern of differentiation and angiogenesis, which is not detectable morphologically. 25270010 4 66 theme II 978:979 arg1 chains 988:993 type II glycan chains 973:993 type II glycan chains 973:993 RESULTS High expression of several classes of glycan was seen de novo in capillary endothelial cells from patients with UIP including small complex and bi/tri-antennary bisected complex N-linked sequences bolund by Concanavalin A and erythro-phytohemagglutinin, respectively, GalNAca1 residues bound by Helix pomatia and Maclura pomifera agglutinins, and L-fucosylated derivatives of type II glycan chains recognized by Ulex europaeus agglutinin-I. 25270010 7 67 theme angiogenesis 1683:1694 arg1 pattern 1652:1658 a pattern 1650:1658 a pattern 1650:1658 CONCLUSION These results may indicate existence of two distinct populations of endothelial cell in UIP with markedly different patterns of glycosylation, reflecting a pattern of differentiation and angiogenesis, which is not detectable morphologically. 25270010 7 67 theme angiogenesis 1683:1694 arg1 detectable 1710:1719 detectable 1710:1719 detectable 1710:1719 CONCLUSION These results may indicate existence of two distinct populations of endothelial cell in UIP with markedly different patterns of glycosylation, reflecting a pattern of differentiation and angiogenesis, which is not detectable morphologically. 25270010 4 68 theme chains 988:993 arg1 derivatives 958:968 L-fucosylated derivatives 944:968 L-fucosylated derivatives of type II glycan chains 944:993 RESULTS High expression of several classes of glycan was seen de novo in capillary endothelial cells from patients with UIP including small complex and bi/tri-antennary bisected complex N-linked sequences bolund by Concanavalin A and erythro-phytohemagglutinin, respectively, GalNAca1 residues bound by Helix pomatia and Maclura pomifera agglutinins, and L-fucosylated derivatives of type II glycan chains recognized by Ulex europaeus agglutinin-I. 25270010 1 69 theme cryptogenic 126:136 arg1 alveolitis 148:157 cryptogenic fibrosing alveolitis 126:157 cryptogenic fibrosing alveolitis 126:157 BACKGROUND The pathological classification of cryptogenic fibrosing alveolitis has been a matter of debate and controversy for histopathologists. 25270010 7 70 theme differentiation 1663:1677 arg1 pattern 1652:1658 a pattern 1650:1658 a pattern 1650:1658 CONCLUSION These results may indicate existence of two distinct populations of endothelial cell in UIP with markedly different patterns of glycosylation, reflecting a pattern of differentiation and angiogenesis, which is not detectable morphologically. 25270010 7 70 theme differentiation 1663:1677 arg1 detectable 1710:1719 detectable 1710:1719 detectable 1710:1719 CONCLUSION These results may indicate existence of two distinct populations of endothelial cell in UIP with markedly different patterns of glycosylation, reflecting a pattern of differentiation and angiogenesis, which is not detectable morphologically. 25270010 4 71 theme L-fucosylated 944:956 arg1 derivatives 958:968 L-fucosylated derivatives 944:968 L-fucosylated derivatives of type II glycan chains 944:993 RESULTS High expression of several classes of glycan was seen de novo in capillary endothelial cells from patients with UIP including small complex and bi/tri-antennary bisected complex N-linked sequences bolund by Concanavalin A and erythro-phytohemagglutinin, respectively, GalNAca1 residues bound by Helix pomatia and Maclura pomifera agglutinins, and L-fucosylated derivatives of type II glycan chains recognized by Ulex europaeus agglutinin-I. 25270010 1 72 dep BACKGROUND 80:89 arg1 classification 108:121 The pathological classification 91:121 The pathological classification of cryptogenic fibrosing alveolitis 91:157 BACKGROUND The pathological classification of cryptogenic fibrosing alveolitis has been a matter of debate and controversy for histopathologists. 25270010 1 72 dep BACKGROUND 80:89 arg1 matter 170:175 a matter 168:175 a matter of debate and controversy for histopathologists 168:223 BACKGROUND The pathological classification of cryptogenic fibrosing alveolitis has been a matter of debate and controversy for histopathologists. 25270010 2 73 theme endothelial 288:298 arg1 cells 300:304 capillary endothelial cells 278:304 capillary endothelial cells in usual interstitial pneumonia (UIP) 278:342 OBJECTIVE To identify and specify the glycotypes of capillary endothelial cells in usual interstitial pneumonia (UIP) compared to those found in normal tissue. 25270010 1 74 theme alveolitis 148:157 arg1 matter 170:175 a matter 168:175 a matter of debate and controversy for histopathologists 168:223 BACKGROUND The pathological classification of cryptogenic fibrosing alveolitis has been a matter of debate and controversy for histopathologists. 25270010 1 74 theme alveolitis 148:157 arg1 classification 108:121 The pathological classification 91:121 The pathological classification of cryptogenic fibrosing alveolitis 91:157 BACKGROUND The pathological classification of cryptogenic fibrosing alveolitis has been a matter of debate and controversy for histopathologists. 25270010 2 75 from cells 300:304 arg1 UIP 339:341 UIP 339:341 UIP 339:341 OBJECTIVE To identify and specify the glycotypes of capillary endothelial cells in usual interstitial pneumonia (UIP) compared to those found in normal tissue. 25270010 2 75 from cells 300:304 arg1 pneumonia 328:336 usual interstitial pneumonia 309:336 usual interstitial pneumonia (UIP) 309:342 OBJECTIVE To identify and specify the glycotypes of capillary endothelial cells in usual interstitial pneumonia (UIP) compared to those found in normal tissue. 25270010 4 76 theme bi/tri-antennary 741:756 arg1 complex 767:773 bi/tri-antennary bisected complex 741:773 bi/tri-antennary bisected complex 741:773 RESULTS High expression of several classes of glycan was seen de novo in capillary endothelial cells from patients with UIP including small complex and bi/tri-antennary bisected complex N-linked sequences bolund by Concanavalin A and erythro-phytohemagglutinin, respectively, GalNAca1 residues bound by Helix pomatia and Maclura pomifera agglutinins, and L-fucosylated derivatives of type II glycan chains recognized by Ulex europaeus agglutinin-I. 25270010 6 77 from contrast 1300:1307 arg1 absent 1365:1370 absent 1365:1370 absent 1365:1370 In contrast, L-fucosylated derivatives of type I glycan chains were absent in cells from cases of UIP when Anguilla anguilla agglutinin was applied, unlike the situation in normal tissue. 25270010 4 78 gly L-fucosylated 944:956 arg1 derivatives 958:968 L-fucosylated derivatives 944:968 L-fucosylated derivatives of type II glycan chains 944:993 RESULTS High expression of several classes of glycan was seen de novo in capillary endothelial cells from patients with UIP including small complex and bi/tri-antennary bisected complex N-linked sequences bolund by Concanavalin A and erythro-phytohemagglutinin, respectively, GalNAca1 residues bound by Helix pomatia and Maclura pomifera agglutinins, and L-fucosylated derivatives of type II glycan chains recognized by Ulex europaeus agglutinin-I. 25270010 2 79 from pneumonia 328:336 arg1 glycotypes 264:273 the glycotypes 260:273 the glycotypes of capillary endothelial cells in usual interstitial pneumonia (UIP) 260:342 OBJECTIVE To identify and specify the glycotypes of capillary endothelial cells in usual interstitial pneumonia (UIP) compared to those found in normal tissue. 25270010 7 80 theme glycosylation 1624:1636 arg1 patterns 1612:1619 markedly different patterns 1593:1619 markedly different patterns of glycosylation 1593:1636 CONCLUSION These results may indicate existence of two distinct populations of endothelial cell in UIP with markedly different patterns of glycosylation, reflecting a pattern of differentiation and angiogenesis, which is not detectable morphologically. 25270010 5 81 theme succinylated 1204:1215 arg1 agglutinin 1228:1237 succinylated Wheat Germ agglutinin 1204:1237 succinylated Wheat Germ agglutinin 1204:1237 Glycans bound by agglutinins from Lycopersicon esculentum (β1,4GlcNAc) and Wisteria floribunda (GalNAc) as well as GlcNAc oligomers bound by Phytolacca americana and succinylated Wheat Germ agglutinin were also seen in the capillary endothelial cells of UIP. 25270010 3 82 dep formalin-fixed 406:419 arg1 paraffin-embedded 422:438 paraffin-embedded 422:438 paraffin-embedded 422:438 METHODS Sections of formalin-fixed, paraffin-embedded blocks from 16 cases of UIP were studied by lectin histochemistry with a panel of 27 biotinylated lectins and an avidin-peroxidase revealing system. 25270010 6 83 theme Anguilla 1404:1411 arg1 anguilla 1413:1420 Anguilla anguilla 1404:1420 Anguilla anguilla agglutinin 1404:1431 In contrast, L-fucosylated derivatives of type I glycan chains were absent in cells from cases of UIP when Anguilla anguilla agglutinin was applied, unlike the situation in normal tissue. 25270010 4 84 dep RESULTS 589:595 arg1 seen 646:649 seen 646:649 seen 646:649 RESULTS High expression of several classes of glycan was seen de novo in capillary endothelial cells from patients with UIP including small complex and bi/tri-antennary bisected complex N-linked sequences bolund by Concanavalin A and erythro-phytohemagglutinin, respectively, GalNAca1 residues bound by Helix pomatia and Maclura pomifera agglutinins, and L-fucosylated derivatives of type II glycan chains recognized by Ulex europaeus agglutinin-I. 25270010 4 85 theme europaeus 1014:1022 arg1 agglutinin-I 1024:1035 Ulex europaeus agglutinin-I 1009:1035 Ulex europaeus agglutinin-I 1009:1035 RESULTS High expression of several classes of glycan was seen de novo in capillary endothelial cells from patients with UIP including small complex and bi/tri-antennary bisected complex N-linked sequences bolund by Concanavalin A and erythro-phytohemagglutinin, respectively, GalNAca1 residues bound by Helix pomatia and Maclura pomifera agglutinins, and L-fucosylated derivatives of type II glycan chains recognized by Ulex europaeus agglutinin-I. 25270010 3 86 theme UIP 464:466 arg1 cases 455:459 16 cases 452:459 16 cases of UIP 452:466 METHODS Sections of formalin-fixed, paraffin-embedded blocks from 16 cases of UIP were studied by lectin histochemistry with a panel of 27 biotinylated lectins and an avidin-peroxidase revealing system. 25270010 0 87 theme glycoprofile 4:15 arg1 patterns 17:24 The glycoprofile patterns 0:24 The glycoprofile patterns of endothelial cells in usual interstitial pneumonia 0:77 The glycoprofile patterns of endothelial cells in usual interstitial pneumonia. 25270010 3 88 from Sections 394:401 arg1 cases 455:459 16 cases 452:459 16 cases of UIP 452:466 METHODS Sections of formalin-fixed, paraffin-embedded blocks from 16 cases of UIP were studied by lectin histochemistry with a panel of 27 biotinylated lectins and an avidin-peroxidase revealing system. 25270010 3 89 theme formalin-fixed 406:419 arg1 blocks 440:445 formalin-fixed, paraffin-embedded blocks 406:445 formalin-fixed, paraffin-embedded blocks from 16 cases of UIP 406:466 METHODS Sections of formalin-fixed, paraffin-embedded blocks from 16 cases of UIP were studied by lectin histochemistry with a panel of 27 biotinylated lectins and an avidin-peroxidase revealing system. 25270010 4 90 theme complex 767:773 arg1 sequences 784:792 small complex and bi/tri-antennary bisected complex N-linked sequences 723:792 small complex and bi/tri-antennary bisected complex N-linked sequences bolund by Concanavalin A and erythro-phytohemagglutinin 723:848 RESULTS High expression of several classes of glycan was seen de novo in capillary endothelial cells from patients with UIP including small complex and bi/tri-antennary bisected complex N-linked sequences bolund by Concanavalin A and erythro-phytohemagglutinin, respectively, GalNAca1 residues bound by Helix pomatia and Maclura pomifera agglutinins, and L-fucosylated derivatives of type II glycan chains recognized by Ulex europaeus agglutinin-I. 25270010 2 91 from glycotypes 264:273 arg1 UIP 339:341 UIP 339:341 UIP 339:341 OBJECTIVE To identify and specify the glycotypes of capillary endothelial cells in usual interstitial pneumonia (UIP) compared to those found in normal tissue. 25270010 2 91 from glycotypes 264:273 arg1 pneumonia 328:336 usual interstitial pneumonia 309:336 usual interstitial pneumonia (UIP) 309:342 OBJECTIVE To identify and specify the glycotypes of capillary endothelial cells in usual interstitial pneumonia (UIP) compared to those found in normal tissue. 25270010 4 92 theme High 597:600 arg1 expression 602:611 High expression 597:611 High expression of several classes of glycan 597:640 RESULTS High expression of several classes of glycan was seen de novo in capillary endothelial cells from patients with UIP including small complex and bi/tri-antennary bisected complex N-linked sequences bolund by Concanavalin A and erythro-phytohemagglutinin, respectively, GalNAca1 residues bound by Helix pomatia and Maclura pomifera agglutinins, and L-fucosylated derivatives of type II glycan chains recognized by Ulex europaeus agglutinin-I. 25270010 4 93 with patients 695:702 arg1 sequences 784:792 small complex and bi/tri-antennary bisected complex N-linked sequences 723:792 small complex and bi/tri-antennary bisected complex N-linked sequences bolund by Concanavalin A and erythro-phytohemagglutinin 723:848 RESULTS High expression of several classes of glycan was seen de novo in capillary endothelial cells from patients with UIP including small complex and bi/tri-antennary bisected complex N-linked sequences bolund by Concanavalin A and erythro-phytohemagglutinin, respectively, GalNAca1 residues bound by Helix pomatia and Maclura pomifera agglutinins, and L-fucosylated derivatives of type II glycan chains recognized by Ulex europaeus agglutinin-I. 25270010 4 93 with patients 695:702 arg1 UIP 709:711 UIP 709:711 UIP including small complex and bi/tri-antennary bisected complex N-linked sequences bolund by Concanavalin A and erythro-phytohemagglutinin 709:848 RESULTS High expression of several classes of glycan was seen de novo in capillary endothelial cells from patients with UIP including small complex and bi/tri-antennary bisected complex N-linked sequences bolund by Concanavalin A and erythro-phytohemagglutinin, respectively, GalNAca1 residues bound by Helix pomatia and Maclura pomifera agglutinins, and L-fucosylated derivatives of type II glycan chains recognized by Ulex europaeus agglutinin-I. 25270010 3 94 theme lectin 484:489 arg1 histochemistry 491:504 lectin histochemistry 484:504 lectin histochemistry with a panel of 27 biotinylated lectins and an avidin-peroxidase revealing system 484:586 METHODS Sections of formalin-fixed, paraffin-embedded blocks from 16 cases of UIP were studied by lectin histochemistry with a panel of 27 biotinylated lectins and an avidin-peroxidase revealing system. 25270010 0 95 theme cells 41:45 arg1 patterns 17:24 The glycoprofile patterns 0:24 The glycoprofile patterns of endothelial cells in usual interstitial pneumonia 0:77 The glycoprofile patterns of endothelial cells in usual interstitial pneumonia. 25270010 7 96 theme different 1602:1610 arg1 patterns 1612:1619 markedly different patterns 1593:1619 markedly different patterns of glycosylation 1593:1636 CONCLUSION These results may indicate existence of two distinct populations of endothelial cell in UIP with markedly different patterns of glycosylation, reflecting a pattern of differentiation and angiogenesis, which is not detectable morphologically. 25270010 4 97 theme GalNAca1 865:872 arg1 residues 874:881 GalNAca1 residues 865:881 GalNAca1 residues 865:881 RESULTS High expression of several classes of glycan was seen de novo in capillary endothelial cells from patients with UIP including small complex and bi/tri-antennary bisected complex N-linked sequences bolund by Concanavalin A and erythro-phytohemagglutinin, respectively, GalNAca1 residues bound by Helix pomatia and Maclura pomifera agglutinins, and L-fucosylated derivatives of type II glycan chains recognized by Ulex europaeus agglutinin-I. 25270010 0 98 theme usual 50:54 arg1 pneumonia 69:77 usual interstitial pneumonia 50:77 usual interstitial pneumonia 50:77 The glycoprofile patterns of endothelial cells in usual interstitial pneumonia. 25270010 5 99 theme Germ 1223:1226 arg1 agglutinin 1228:1237 succinylated Wheat Germ agglutinin 1204:1237 succinylated Wheat Germ agglutinin 1204:1237 Glycans bound by agglutinins from Lycopersicon esculentum (β1,4GlcNAc) and Wisteria floribunda (GalNAc) as well as GlcNAc oligomers bound by Phytolacca americana and succinylated Wheat Germ agglutinin were also seen in the capillary endothelial cells of UIP. 25270010 4 100 theme glycan 635:640 arg1 classes 624:630 several classes 616:630 several classes of glycan 616:640 RESULTS High expression of several classes of glycan was seen de novo in capillary endothelial cells from patients with UIP including small complex and bi/tri-antennary bisected complex N-linked sequences bolund by Concanavalin A and erythro-phytohemagglutinin, respectively, GalNAca1 residues bound by Helix pomatia and Maclura pomifera agglutinins, and L-fucosylated derivatives of type II glycan chains recognized by Ulex europaeus agglutinin-I. 25270010 7 101 theme endothelial 1564:1574 arg1 cell 1576:1579 endothelial cell 1564:1579 endothelial cell 1564:1579 CONCLUSION These results may indicate existence of two distinct populations of endothelial cell in UIP with markedly different patterns of glycosylation, reflecting a pattern of differentiation and angiogenesis, which is not detectable morphologically. 25270010 3 102 theme lectins 538:544 arg1 panel 513:517 a panel 511:517 a panel of 27 biotinylated lectins 511:544 METHODS Sections of formalin-fixed, paraffin-embedded blocks from 16 cases of UIP were studied by lectin histochemistry with a panel of 27 biotinylated lectins and an avidin-peroxidase revealing system. 25270010 3 102 theme lectins 538:544 arg1 system 581:586 an avidin-peroxidase revealing system 550:586 an avidin-peroxidase revealing system 550:586 METHODS Sections of formalin-fixed, paraffin-embedded blocks from 16 cases of UIP were studied by lectin histochemistry with a panel of 27 biotinylated lectins and an avidin-peroxidase revealing system. 24191663 5 0 theme gene 685:688 arg1 cluster 690:696 the corresponding gene cluster 667:696 the corresponding gene cluster 667:696 Consistently, the corresponding gene cluster encodes, in addition to the LanKC enzyme characteristic of this lanthipeptide class, a glycosyl transferase. 24191663 5 0 theme gene 685:688 arg1 transferase 794:804 a glycosyl transferase 783:804 a glycosyl transferase 783:804 Consistently, the corresponding gene cluster encodes, in addition to the LanKC enzyme characteristic of this lanthipeptide class, a glycosyl transferase. 24191663 0 1 with lanthipeptide 36:48 arg1 activity 78:85 marked antinociceptive activity 55:85 marked antinociceptive activity 55:85 A glycosylated, labionin-containing lanthipeptide with marked antinociceptive activity. 24191663 5 2 dep enzyme 732:737 arg1 addition 710:717 addition 710:717 addition 710:717 Consistently, the corresponding gene cluster encodes, in addition to the LanKC enzyme characteristic of this lanthipeptide class, a glycosyl transferase. 24191663 2 3 theme new 375:377 arg1 lanthipeptide 379:391 a new lanthipeptide 373:391 a new lanthipeptide produced by an Actinoplanes sp 373:422 In the course of a screening program aimed at finding bacterial cell wall inhibitors, we discovered a new lanthipeptide produced by an Actinoplanes sp. 24191663 4 4 theme 6-deoxyhexose 598:610 arg1 moiety 612:617 a 6-deoxyhexose moiety 596:617 a 6-deoxyhexose moiety N-linked to a tryptophan residue 596:650 Unique among lanthipeptides, it carries a 6-deoxyhexose moiety N-linked to a tryptophan residue. 24191663 3 5 theme amino 474:478 arg1 acids 480:484 22 amino acids 471:484 22 amino acids 471:484 The molecule, designated NAI-112, consists of 22 amino acids and contains an N-terminal labionin and a C-terminal methyl-labionin. 24191663 4 6 contain carries 588:594 arg1 it 585:586 it 585:586 it 585:586 Unique among lanthipeptides, it carries a 6-deoxyhexose moiety N-linked to a tryptophan residue. 24191663 4 6 contain carries 588:594 arg2 moiety 612:617 a 6-deoxyhexose moiety 596:617 a 6-deoxyhexose moiety N-linked to a tryptophan residue 596:650 Unique among lanthipeptides, it carries a 6-deoxyhexose moiety N-linked to a tryptophan residue. 24191663 4 7 theme N-linked 619:626 arg1 moiety 612:617 a 6-deoxyhexose moiety 596:617 a 6-deoxyhexose moiety N-linked to a tryptophan residue 596:650 Unique among lanthipeptides, it carries a 6-deoxyhexose moiety N-linked to a tryptophan residue. 24191663 5 8 theme class 776:780 arg1 characteristic 739:752 characteristic 739:752 characteristic 739:752 Consistently, the corresponding gene cluster encodes, in addition to the LanKC enzyme characteristic of this lanthipeptide class, a glycosyl transferase. 24191663 3 9 contain contains 490:497 arg2 methyl-labionin 539:553 a C-terminal methyl-labionin 526:553 a C-terminal methyl-labionin 526:553 The molecule, designated NAI-112, consists of 22 amino acids and contains an N-terminal labionin and a C-terminal methyl-labionin. 24191663 3 9 contain contains 490:497 arg1 molecule 429:436 The molecule 425:436 The molecule 425:436 The molecule, designated NAI-112, consists of 22 amino acids and contains an N-terminal labionin and a C-terminal methyl-labionin. 24191663 3 9 contain contains 490:497 arg2 labionin 513:520 an N-terminal labionin 499:520 an N-terminal labionin 499:520 The molecule, designated NAI-112, consists of 22 amino acids and contains an N-terminal labionin and a C-terminal methyl-labionin. 24191663 1 10 dep synthesized 128:138 arg1 modified 162:169 modified 162:169 modified 162:169 Among the growing family of ribosomally synthesized, post-translationally modified peptides, particularly intriguing are class III lanthipeptides containing the triamino acid labionin. 24191663 6 11 from symptoms 934:941 arg1 mice 946:949 mice 946:949 mice 946:949 Despite possessing weak antibacterial activity, NAI-112 is effective in experimental models of nociceptive pain, reducing pain symptoms in mice in both the formalin and the chronic constriction injury tests. 24191663 6 12 theme pain 929:932 arg1 symptoms 934:941 pain symptoms 929:941 pain symptoms in mice 929:949 Despite possessing weak antibacterial activity, NAI-112 is effective in experimental models of nociceptive pain, reducing pain symptoms in mice in both the formalin and the chronic constriction injury tests. 24191663 6 13 theme antibacterial 831:843 arg1 activity 845:852 weak antibacterial activity 826:852 weak antibacterial activity 826:852 Despite possessing weak antibacterial activity, NAI-112 is effective in experimental models of nociceptive pain, reducing pain symptoms in mice in both the formalin and the chronic constriction injury tests. 24191663 2 14 theme program 302:308 arg1 course 280:285 the course 276:285 the course of a screening program aimed at finding bacterial cell wall inhibitors 276:356 In the course of a screening program aimed at finding bacterial cell wall inhibitors, we discovered a new lanthipeptide produced by an Actinoplanes sp. 24191663 3 15 theme N-terminal 502:511 arg1 labionin 513:520 an N-terminal labionin 499:520 an N-terminal labionin 499:520 The molecule, designated NAI-112, consists of 22 amino acids and contains an N-terminal labionin and a C-terminal methyl-labionin. 24191663 1 16 theme class 209:213 arg1 lanthipeptides 219:232 class III lanthipeptides 209:232 class III lanthipeptides containing the triamino acid labionin 209:270 Among the growing family of ribosomally synthesized, post-translationally modified peptides, particularly intriguing are class III lanthipeptides containing the triamino acid labionin. 24191663 1 16 theme class 209:213 arg1 intriguing 194:203 intriguing 194:203 intriguing 194:203 Among the growing family of ribosomally synthesized, post-translationally modified peptides, particularly intriguing are class III lanthipeptides containing the triamino acid labionin. 24191663 0 17 theme glycosylated 2:13 arg1 lanthipeptide 36:48 A glycosylated, labionin-containing lanthipeptide 0:48 A glycosylated, labionin-containing lanthipeptide with marked antinociceptive activity 0:85 A glycosylated, labionin-containing lanthipeptide with marked antinociceptive activity. 24191663 6 18 theme weak 826:829 arg1 activity 845:852 weak antibacterial activity 826:852 weak antibacterial activity 826:852 Despite possessing weak antibacterial activity, NAI-112 is effective in experimental models of nociceptive pain, reducing pain symptoms in mice in both the formalin and the chronic constriction injury tests. 24191663 1 19 theme growing 98:104 arg1 family 106:111 the growing family 94:111 the growing family of ribosomally synthesized, post-translationally modified peptides 94:178 Among the growing family of ribosomally synthesized, post-translationally modified peptides, particularly intriguing are class III lanthipeptides containing the triamino acid labionin. 24191663 2 20 theme Actinoplanes 408:419 arg1 sp 421:422 an Actinoplanes sp 405:422 an Actinoplanes sp 405:422 In the course of a screening program aimed at finding bacterial cell wall inhibitors, we discovered a new lanthipeptide produced by an Actinoplanes sp. 24191663 5 21 theme corresponding 671:683 arg1 cluster 690:696 the corresponding gene cluster 667:696 the corresponding gene cluster 667:696 Consistently, the corresponding gene cluster encodes, in addition to the LanKC enzyme characteristic of this lanthipeptide class, a glycosyl transferase. 24191663 5 21 theme corresponding 671:683 arg1 transferase 794:804 a glycosyl transferase 783:804 a glycosyl transferase 783:804 Consistently, the corresponding gene cluster encodes, in addition to the LanKC enzyme characteristic of this lanthipeptide class, a glycosyl transferase. 24191663 2 22 theme wall 342:345 arg1 inhibitors 347:356 bacterial cell wall inhibitors 327:356 bacterial cell wall inhibitors 327:356 In the course of a screening program aimed at finding bacterial cell wall inhibitors, we discovered a new lanthipeptide produced by an Actinoplanes sp. 24191663 6 23 dep formalin 963:970 arg1 tests 1008:1012 tests 1008:1012 tests 1008:1012 Despite possessing weak antibacterial activity, NAI-112 is effective in experimental models of nociceptive pain, reducing pain symptoms in mice in both the formalin and the chronic constriction injury tests. 24191663 6 24 from models 892:897 arg1 effective 866:874 effective 866:874 effective 866:874 Despite possessing weak antibacterial activity, NAI-112 is effective in experimental models of nociceptive pain, reducing pain symptoms in mice in both the formalin and the chronic constriction injury tests. 24191663 5 25 theme LanKC 726:730 arg1 enzyme 732:737 the LanKC enzyme 722:737 the LanKC enzyme characteristic of this lanthipeptide class 722:780 Consistently, the corresponding gene cluster encodes, in addition to the LanKC enzyme characteristic of this lanthipeptide class, a glycosyl transferase. 24191663 2 26 theme cell 337:340 arg1 inhibitors 347:356 bacterial cell wall inhibitors 327:356 bacterial cell wall inhibitors 327:356 In the course of a screening program aimed at finding bacterial cell wall inhibitors, we discovered a new lanthipeptide produced by an Actinoplanes sp. 24191663 7 27 theme effective 1108:1116 arg1 lanthipeptide 1094:1106 a lanthipeptide 1092:1106 a lanthipeptide effective against nociceptive pain 1092:1141 Thus, NAI-112 represents, after the labyrinthopeptins, the second example of a lanthipeptide effective against nociceptive pain. 24191663 2 28 theme bacterial 327:335 arg1 inhibitors 347:356 bacterial cell wall inhibitors 327:356 bacterial cell wall inhibitors 327:356 In the course of a screening program aimed at finding bacterial cell wall inhibitors, we discovered a new lanthipeptide produced by an Actinoplanes sp. 24191663 3 29 theme C-terminal 528:537 arg1 methyl-labionin 539:553 a C-terminal methyl-labionin 526:553 a C-terminal methyl-labionin 526:553 The molecule, designated NAI-112, consists of 22 amino acids and contains an N-terminal labionin and a C-terminal methyl-labionin. 24191663 6 30 theme constriction 988:999 arg1 injury 1001:1006 the chronic constriction injury 976:1006 the chronic constriction injury 976:1006 Despite possessing weak antibacterial activity, NAI-112 is effective in experimental models of nociceptive pain, reducing pain symptoms in mice in both the formalin and the chronic constriction injury tests. 24191663 5 31 theme characteristic 739:752 arg1 enzyme 732:737 the LanKC enzyme 722:737 the LanKC enzyme characteristic of this lanthipeptide class 722:780 Consistently, the corresponding gene cluster encodes, in addition to the LanKC enzyme characteristic of this lanthipeptide class, a glycosyl transferase. 24191663 6 32 theme pain 914:917 arg1 models 892:897 experimental models 879:897 experimental models of nociceptive pain 879:917 Despite possessing weak antibacterial activity, NAI-112 is effective in experimental models of nociceptive pain, reducing pain symptoms in mice in both the formalin and the chronic constriction injury tests. 24191663 1 33 theme triamino 249:256 arg1 labionin 263:270 the triamino acid labionin 245:270 the triamino acid labionin 245:270 Among the growing family of ribosomally synthesized, post-translationally modified peptides, particularly intriguing are class III lanthipeptides containing the triamino acid labionin. 24191663 6 34 from effective 866:874 arg1 models 892:897 experimental models 879:897 experimental models of nociceptive pain 879:917 Despite possessing weak antibacterial activity, NAI-112 is effective in experimental models of nociceptive pain, reducing pain symptoms in mice in both the formalin and the chronic constriction injury tests. 24191663 6 35 theme chronic 980:986 arg1 injury 1001:1006 the chronic constriction injury 976:1006 the chronic constriction injury 976:1006 Despite possessing weak antibacterial activity, NAI-112 is effective in experimental models of nociceptive pain, reducing pain symptoms in mice in both the formalin and the chronic constriction injury tests. 24191663 6 36 theme nociceptive 902:912 arg1 pain 914:917 nociceptive pain 902:917 nociceptive pain 902:917 Despite possessing weak antibacterial activity, NAI-112 is effective in experimental models of nociceptive pain, reducing pain symptoms in mice in both the formalin and the chronic constriction injury tests. 24191663 0 37 gly glycosylated 2:13 arg1 lanthipeptide 36:48 A glycosylated, labionin-containing lanthipeptide 0:48 A glycosylated, labionin-containing lanthipeptide with marked antinociceptive activity 0:85 A glycosylated, labionin-containing lanthipeptide with marked antinociceptive activity. 24191663 1 38 theme acid 258:261 arg1 labionin 263:270 the triamino acid labionin 245:270 the triamino acid labionin 245:270 Among the growing family of ribosomally synthesized, post-translationally modified peptides, particularly intriguing are class III lanthipeptides containing the triamino acid labionin. 24191663 0 39 theme antinociceptive 62:76 arg1 activity 78:85 marked antinociceptive activity 55:85 marked antinociceptive activity 55:85 A glycosylated, labionin-containing lanthipeptide with marked antinociceptive activity. 24191663 7 40 theme second 1074:1079 arg1 example 1081:1087 the second example 1070:1087 the second example of a lanthipeptide effective against nociceptive pain 1070:1141 Thus, NAI-112 represents, after the labyrinthopeptins, the second example of a lanthipeptide effective against nociceptive pain. 24191663 1 41 theme synthesized 128:138 arg1 peptides 171:178 ribosomally synthesized, post-translationally modified peptides 116:178 ribosomally synthesized, post-translationally modified peptides 116:178 Among the growing family of ribosomally synthesized, post-translationally modified peptides, particularly intriguing are class III lanthipeptides containing the triamino acid labionin. 24191663 0 42 theme marked 55:60 arg1 activity 78:85 marked antinociceptive activity 55:85 marked antinociceptive activity 55:85 A glycosylated, labionin-containing lanthipeptide with marked antinociceptive activity. 24191663 7 43 theme lanthipeptide 1094:1106 arg1 example 1081:1087 the second example 1070:1087 the second example of a lanthipeptide effective against nociceptive pain 1070:1141 Thus, NAI-112 represents, after the labyrinthopeptins, the second example of a lanthipeptide effective against nociceptive pain. 24191663 6 44 theme experimental 879:890 arg1 models 892:897 experimental models 879:897 experimental models of nociceptive pain 879:917 Despite possessing weak antibacterial activity, NAI-112 is effective in experimental models of nociceptive pain, reducing pain symptoms in mice in both the formalin and the chronic constriction injury tests. 24191663 4 45 link N-linked 619:626 arg1 moiety 612:617 a 6-deoxyhexose moiety 596:617 a 6-deoxyhexose moiety N-linked to a tryptophan residue 596:650 Unique among lanthipeptides, it carries a 6-deoxyhexose moiety N-linked to a tryptophan residue. 24191663 2 46 theme screening 292:300 arg1 program 302:308 a screening program 290:308 a screening program aimed at finding bacterial cell wall inhibitors 290:356 In the course of a screening program aimed at finding bacterial cell wall inhibitors, we discovered a new lanthipeptide produced by an Actinoplanes sp. 24191663 4 47 theme tryptophan 633:642 arg1 residue 644:650 a tryptophan residue 631:650 a tryptophan residue 631:650 Unique among lanthipeptides, it carries a 6-deoxyhexose moiety N-linked to a tryptophan residue. 24191663 7 48 theme nociceptive 1126:1136 arg1 pain 1138:1141 nociceptive pain 1126:1141 nociceptive pain 1126:1141 Thus, NAI-112 represents, after the labyrinthopeptins, the second example of a lanthipeptide effective against nociceptive pain. 24191663 1 49 contain containing 234:243 arg2 labionin 263:270 the triamino acid labionin 245:270 the triamino acid labionin 245:270 Among the growing family of ribosomally synthesized, post-translationally modified peptides, particularly intriguing are class III lanthipeptides containing the triamino acid labionin. 24191663 1 49 contain containing 234:243 arg1 lanthipeptides 219:232 class III lanthipeptides 209:232 class III lanthipeptides containing the triamino acid labionin 209:270 Among the growing family of ribosomally synthesized, post-translationally modified peptides, particularly intriguing are class III lanthipeptides containing the triamino acid labionin. 24191663 1 49 contain containing 234:243 arg1 intriguing 194:203 intriguing 194:203 intriguing 194:203 Among the growing family of ribosomally synthesized, post-translationally modified peptides, particularly intriguing are class III lanthipeptides containing the triamino acid labionin. 24191663 0 50 dep glycosylated 2:13 arg1 labionin-containing 16:34 labionin-containing 16:34 labionin-containing 16:34 A glycosylated, labionin-containing lanthipeptide with marked antinociceptive activity. 24191663 1 51 theme peptides 171:178 arg1 family 106:111 the growing family 94:111 the growing family of ribosomally synthesized, post-translationally modified peptides 94:178 Among the growing family of ribosomally synthesized, post-translationally modified peptides, particularly intriguing are class III lanthipeptides containing the triamino acid labionin. 24191663 5 52 theme glycosyl 785:792 arg1 cluster 690:696 the corresponding gene cluster 667:696 the corresponding gene cluster 667:696 Consistently, the corresponding gene cluster encodes, in addition to the LanKC enzyme characteristic of this lanthipeptide class, a glycosyl transferase. 24191663 5 52 theme glycosyl 785:792 arg1 transferase 794:804 a glycosyl transferase 783:804 a glycosyl transferase 783:804 Consistently, the corresponding gene cluster encodes, in addition to the LanKC enzyme characteristic of this lanthipeptide class, a glycosyl transferase. 24191663 5 53 theme lanthipeptide 762:774 arg1 class 776:780 this lanthipeptide class 757:780 this lanthipeptide class 757:780 Consistently, the corresponding gene cluster encodes, in addition to the LanKC enzyme characteristic of this lanthipeptide class, a glycosyl transferase. 27641538 0 0 theme crowding 86:93 arg1 threshold 95:103 a molecular crowding threshold 74:103 a molecular crowding threshold 74:103 N-glycosylation enables high lateral mobility of GPI-anchored proteins at a molecular crowding threshold. 27641538 8 1 theme molecular 1034:1042 arg1 insulators 1044:1053 molecular insulators 1034:1053 molecular insulators that reduce retarding intermolecular interactions allowing membrane proteins 1034:1130 Importantly, our experiments show that N-linked glycans act as molecular insulators that reduce retarding intermolecular interactions allowing membrane proteins to function correctly even when densely packed. 27641538 8 1 theme molecular 1034:1042 arg1 glycans 1019:1025 N-linked glycans 1010:1025 N-linked glycans 1010:1025 Importantly, our experiments show that N-linked glycans act as molecular insulators that reduce retarding intermolecular interactions allowing membrane proteins to function correctly even when densely packed. 27641538 3 2 gly glycoprotein 513:524 arg1 VSG 527:529 VSG 527:529 VSG 527:529 African trypanosomes, however, feature a uniform surface coat that is dominated by a single type of variant surface glycoprotein (VSG). 27641538 3 2 gly glycoprotein 513:524 arg1 glycoprotein 513:524 variant surface glycoprotein 497:524 variant surface glycoprotein (VSG) 497:530 African trypanosomes, however, feature a uniform surface coat that is dominated by a single type of variant surface glycoprotein (VSG). 27641538 1 3 theme proteins 245:252 arg1 diffusion 223:231 the diffusion 219:231 the diffusion of membrane proteins 219:252 The protein density in biological membranes can be extraordinarily high, but the impact of molecular crowding on the diffusion of membrane proteins has not been studied systematically in a natural system. 27641538 0 4 theme molecular 76:84 arg1 threshold 95:103 a molecular crowding threshold 74:103 a molecular crowding threshold 74:103 N-glycosylation enables high lateral mobility of GPI-anchored proteins at a molecular crowding threshold. 27641538 2 5 theme proteome 341:348 arg1 diversity 315:323 The diversity 311:323 The diversity of the membrane proteome of most cells 311:362 The diversity of the membrane proteome of most cells may preclude systematic studies. 27641538 5 6 theme molecular 729:737 arg1 threshold 748:756 a specific molecular crowding threshold 718:756 a specific molecular crowding threshold (MCT) 718:762 Our results suggest that a specific molecular crowding threshold (MCT) limits diffusion and hence affects protein function. 27641538 5 6 theme molecular 729:737 arg1 MCT 759:761 MCT 759:761 MCT 759:761 Our results suggest that a specific molecular crowding threshold (MCT) limits diffusion and hence affects protein function. 27641538 4 7 from density-dependence 551:568 arg1 membranes 682:690 artificial membranes 671:690 artificial membranes 671:690 Here we study the density-dependence of the diffusion of different glycosylphosphatidylinositol-anchored VSG-types on living cells and in artificial membranes. 27641538 4 7 from density-dependence 551:568 arg1 cells 658:662 living cells 651:662 living cells 651:662 Here we study the density-dependence of the diffusion of different glycosylphosphatidylinositol-anchored VSG-types on living cells and in artificial membranes. 27641538 3 8 theme single 482:487 arg1 type 489:492 a single type 480:492 a single type of variant surface glycoprotein (VSG) 480:530 African trypanosomes, however, feature a uniform surface coat that is dominated by a single type of variant surface glycoprotein (VSG). 27641538 8 9 theme retarding 1067:1075 arg1 interactions 1092:1103 retarding intermolecular interactions 1067:1103 retarding intermolecular interactions allowing membrane proteins 1067:1130 Importantly, our experiments show that N-linked glycans act as molecular insulators that reduce retarding intermolecular interactions allowing membrane proteins to function correctly even when densely packed. 27641538 4 10 theme glycosylphosphatidylinositol-anchored 600:636 arg1 VSG-types 638:646 different glycosylphosphatidylinositol-anchored VSG-types 590:646 different glycosylphosphatidylinositol-anchored VSG-types 590:646 Here we study the density-dependence of the diffusion of different glycosylphosphatidylinositol-anchored VSG-types on living cells and in artificial membranes. 27641538 3 11 theme surface 505:511 arg1 VSG 527:529 VSG 527:529 VSG 527:529 African trypanosomes, however, feature a uniform surface coat that is dominated by a single type of variant surface glycoprotein (VSG). 27641538 3 11 theme surface 505:511 arg1 glycoprotein 513:524 variant surface glycoprotein 497:524 variant surface glycoprotein (VSG) 497:530 African trypanosomes, however, feature a uniform surface coat that is dominated by a single type of variant surface glycoprotein (VSG). 27641538 4 12 theme artificial 671:680 arg1 membranes 682:690 artificial membranes 671:690 artificial membranes 671:690 Here we study the density-dependence of the diffusion of different glycosylphosphatidylinositol-anchored VSG-types on living cells and in artificial membranes. 27641538 3 13 theme African 397:403 arg1 trypanosomes 405:416 African trypanosomes 397:416 African trypanosomes 397:416 African trypanosomes, however, feature a uniform surface coat that is dominated by a single type of variant surface glycoprotein (VSG). 27641538 8 14 theme N-linked 1010:1017 arg1 insulators 1044:1053 molecular insulators 1034:1053 molecular insulators that reduce retarding intermolecular interactions allowing membrane proteins 1034:1130 Importantly, our experiments show that N-linked glycans act as molecular insulators that reduce retarding intermolecular interactions allowing membrane proteins to function correctly even when densely packed. 27641538 8 14 theme N-linked 1010:1017 arg1 glycans 1019:1025 N-linked glycans 1010:1025 N-linked glycans 1010:1025 Importantly, our experiments show that N-linked glycans act as molecular insulators that reduce retarding intermolecular interactions allowing membrane proteins to function correctly even when densely packed. 27641538 3 15 theme glycoprotein 513:524 arg1 type 489:492 a single type 480:492 a single type of variant surface glycoprotein (VSG) 480:530 African trypanosomes, however, feature a uniform surface coat that is dominated by a single type of variant surface glycoprotein (VSG). 27641538 2 16 theme systematic 377:386 arg1 studies 388:394 systematic studies 377:394 systematic studies 377:394 The diversity of the membrane proteome of most cells may preclude systematic studies. 27641538 4 17 theme living 651:656 arg1 cells 658:662 living cells 651:662 living cells 651:662 Here we study the density-dependence of the diffusion of different glycosylphosphatidylinositol-anchored VSG-types on living cells and in artificial membranes. 27641538 8 18 theme intermolecular 1077:1090 arg1 interactions 1092:1103 retarding intermolecular interactions 1067:1103 retarding intermolecular interactions allowing membrane proteins 1067:1130 Importantly, our experiments show that N-linked glycans act as molecular insulators that reduce retarding intermolecular interactions allowing membrane proteins to function correctly even when densely packed. 27641538 1 19 from density 118:124 arg1 membranes 140:148 biological membranes 129:148 biological membranes 129:148 The protein density in biological membranes can be extraordinarily high, but the impact of molecular crowding on the diffusion of membrane proteins has not been studied systematically in a natural system. 27641538 6 20 from Obstacles 817:825 arg1 form 834:837 the form 830:837 the form of heterologous proteins 830:862 Obstacles in the form of heterologous proteins compromise the diffusion coefficient and the MCT. 27641538 0 21 theme lateral 29:35 arg1 mobility 37:44 high lateral mobility 24:44 high lateral mobility of GPI-anchored proteins 24:69 N-glycosylation enables high lateral mobility of GPI-anchored proteins at a molecular crowding threshold. 27641538 8 22 theme membrane 1114:1121 arg1 proteins 1123:1130 membrane proteins 1114:1130 membrane proteins 1114:1130 Importantly, our experiments show that N-linked glycans act as molecular insulators that reduce retarding intermolecular interactions allowing membrane proteins to function correctly even when densely packed. 27641538 4 23 theme VSG-types 638:646 arg1 diffusion 577:585 the diffusion 573:585 the diffusion of different glycosylphosphatidylinositol-anchored VSG-types 573:646 Here we study the density-dependence of the diffusion of different glycosylphosphatidylinositol-anchored VSG-types on living cells and in artificial membranes. 27641538 0 24 theme high 24:27 arg1 mobility 37:44 high lateral mobility 24:44 high lateral mobility of GPI-anchored proteins 24:69 N-glycosylation enables high lateral mobility of GPI-anchored proteins at a molecular crowding threshold. 27641538 6 25 theme diffusion 879:887 arg1 coefficient 889:899 the diffusion coefficient 875:899 the diffusion coefficient 875:899 Obstacles in the form of heterologous proteins compromise the diffusion coefficient and the MCT. 27641538 1 26 theme protein 110:116 arg1 density 118:124 The protein density 106:124 The protein density in biological membranes 106:148 The protein density in biological membranes can be extraordinarily high, but the impact of molecular crowding on the diffusion of membrane proteins has not been studied systematically in a natural system. 27641538 1 26 theme protein 110:116 arg1 high 173:176 high 173:176 high 173:176 The protein density in biological membranes can be extraordinarily high, but the impact of molecular crowding on the diffusion of membrane proteins has not been studied systematically in a natural system. 27641538 1 27 theme molecular 197:205 arg1 crowding 207:214 molecular crowding 197:214 molecular crowding 197:214 The protein density in biological membranes can be extraordinarily high, but the impact of molecular crowding on the diffusion of membrane proteins has not been studied systematically in a natural system. 27641538 3 28 theme uniform 438:444 arg1 coat 454:457 a uniform surface coat 436:457 a uniform surface coat that is dominated by a single type of variant surface glycoprotein (VSG) 436:530 African trypanosomes, however, feature a uniform surface coat that is dominated by a single type of variant surface glycoprotein (VSG). 27641538 1 29 theme crowding 207:214 arg1 impact 187:192 the impact 183:192 the impact of molecular crowding on the diffusion of membrane proteins 183:252 The protein density in biological membranes can be extraordinarily high, but the impact of molecular crowding on the diffusion of membrane proteins has not been studied systematically in a natural system. 27641538 1 30 theme natural 295:301 arg1 system 303:308 a natural system 293:308 a natural system 293:308 The protein density in biological membranes can be extraordinarily high, but the impact of molecular crowding on the diffusion of membrane proteins has not been studied systematically in a natural system. 27641538 5 31 theme specific 720:727 arg1 threshold 748:756 a specific molecular crowding threshold 718:756 a specific molecular crowding threshold (MCT) 718:762 Our results suggest that a specific molecular crowding threshold (MCT) limits diffusion and hence affects protein function. 27641538 5 31 theme specific 720:727 arg1 MCT 759:761 MCT 759:761 MCT 759:761 Our results suggest that a specific molecular crowding threshold (MCT) limits diffusion and hence affects protein function. 27641538 5 32 theme crowding 739:746 arg1 threshold 748:756 a specific molecular crowding threshold 718:756 a specific molecular crowding threshold (MCT) 718:762 Our results suggest that a specific molecular crowding threshold (MCT) limits diffusion and hence affects protein function. 27641538 5 32 theme crowding 739:746 arg1 MCT 759:761 MCT 759:761 MCT 759:761 Our results suggest that a specific molecular crowding threshold (MCT) limits diffusion and hence affects protein function. 27641538 3 33 theme surface 446:452 arg1 coat 454:457 a uniform surface coat 436:457 a uniform surface coat that is dominated by a single type of variant surface glycoprotein (VSG) 436:530 African trypanosomes, however, feature a uniform surface coat that is dominated by a single type of variant surface glycoprotein (VSG). 27641538 0 34 theme proteins 62:69 arg1 mobility 37:44 high lateral mobility 24:44 high lateral mobility of GPI-anchored proteins 24:69 N-glycosylation enables high lateral mobility of GPI-anchored proteins at a molecular crowding threshold. 27641538 5 35 theme protein 799:805 arg1 function 807:814 protein function 799:814 protein function 799:814 Our results suggest that a specific molecular crowding threshold (MCT) limits diffusion and hence affects protein function. 27641538 6 36 theme proteins 855:862 arg1 form 834:837 the form 830:837 the form of heterologous proteins 830:862 Obstacles in the form of heterologous proteins compromise the diffusion coefficient and the MCT. 27641538 2 37 theme membrane 332:339 arg1 proteome 341:348 the membrane proteome 328:348 the membrane proteome of most cells 328:362 The diversity of the membrane proteome of most cells may preclude systematic studies. 27641538 0 38 theme GPI-anchored 49:60 arg1 proteins 62:69 GPI-anchored proteins 49:69 GPI-anchored proteins 49:69 N-glycosylation enables high lateral mobility of GPI-anchored proteins at a molecular crowding threshold. 27641538 6 39 theme heterologous 842:853 arg1 proteins 855:862 heterologous proteins 842:862 heterologous proteins 842:862 Obstacles in the form of heterologous proteins compromise the diffusion coefficient and the MCT. 27641538 7 40 theme trypanosome 918:928 arg1 VSG-coat 930:937 The trypanosome VSG-coat 914:937 The trypanosome VSG-coat 914:937 The trypanosome VSG-coat operates very close to its MCT. 27641538 1 41 theme biological 129:138 arg1 membranes 140:148 biological membranes 129:148 biological membranes 129:148 The protein density in biological membranes can be extraordinarily high, but the impact of molecular crowding on the diffusion of membrane proteins has not been studied systematically in a natural system. 27641538 4 42 theme diffusion 577:585 arg1 density-dependence 551:568 the density-dependence 547:568 the density-dependence of the diffusion of different glycosylphosphatidylinositol-anchored VSG-types on living cells and in artificial membranes 547:690 Here we study the density-dependence of the diffusion of different glycosylphosphatidylinositol-anchored VSG-types on living cells and in artificial membranes. 27641538 3 43 theme variant 497:503 arg1 VSG 527:529 VSG 527:529 VSG 527:529 African trypanosomes, however, feature a uniform surface coat that is dominated by a single type of variant surface glycoprotein (VSG). 27641538 3 43 theme variant 497:503 arg1 glycoprotein 513:524 variant surface glycoprotein 497:524 variant surface glycoprotein (VSG) 497:530 African trypanosomes, however, feature a uniform surface coat that is dominated by a single type of variant surface glycoprotein (VSG). 27641538 1 44 from impact 187:192 arg1 diffusion 223:231 the diffusion 219:231 the diffusion of membrane proteins 219:252 The protein density in biological membranes can be extraordinarily high, but the impact of molecular crowding on the diffusion of membrane proteins has not been studied systematically in a natural system. 27641538 2 45 theme cells 358:362 arg1 proteome 341:348 the membrane proteome 328:348 the membrane proteome of most cells 328:362 The diversity of the membrane proteome of most cells may preclude systematic studies. 27641538 4 46 theme different 590:598 arg1 VSG-types 638:646 different glycosylphosphatidylinositol-anchored VSG-types 590:646 different glycosylphosphatidylinositol-anchored VSG-types 590:646 Here we study the density-dependence of the diffusion of different glycosylphosphatidylinositol-anchored VSG-types on living cells and in artificial membranes. 27641538 8 47 link N-linked 1010:1017 arg1 insulators 1044:1053 molecular insulators 1034:1053 molecular insulators that reduce retarding intermolecular interactions allowing membrane proteins 1034:1130 Importantly, our experiments show that N-linked glycans act as molecular insulators that reduce retarding intermolecular interactions allowing membrane proteins to function correctly even when densely packed. 27641538 8 47 link N-linked 1010:1017 arg1 glycans 1019:1025 N-linked glycans 1010:1025 N-linked glycans 1010:1025 Importantly, our experiments show that N-linked glycans act as molecular insulators that reduce retarding intermolecular interactions allowing membrane proteins to function correctly even when densely packed. 27641538 2 48 theme most 353:356 arg1 cells 358:362 most cells 353:362 most cells 353:362 The diversity of the membrane proteome of most cells may preclude systematic studies. 27641538 1 49 theme membrane 236:243 arg1 proteins 245:252 membrane proteins 236:252 membrane proteins 236:252 The protein density in biological membranes can be extraordinarily high, but the impact of molecular crowding on the diffusion of membrane proteins has not been studied systematically in a natural system. 27256912 1 0 theme cholesterol 190:200 arg1 target 247:252 a therapeutic target 233:252 a therapeutic target to raise HDL cholesterol 233:277 Hydroxyl 1,2-diphenylethanamine analogs were identified as potent inhibitors of cholesterol ester transfer protein (CETP), a therapeutic target to raise HDL cholesterol. 27256912 1 0 theme cholesterol 190:200 arg1 CETP 226:229 CETP 226:229 CETP 226:229 Hydroxyl 1,2-diphenylethanamine analogs were identified as potent inhibitors of cholesterol ester transfer protein (CETP), a therapeutic target to raise HDL cholesterol. 27256912 1 0 theme cholesterol 190:200 arg1 protein 217:223 cholesterol ester transfer protein 190:223 cholesterol ester transfer protein (CETP) 190:230 Hydroxyl 1,2-diphenylethanamine analogs were identified as potent inhibitors of cholesterol ester transfer protein (CETP), a therapeutic target to raise HDL cholesterol. 27256912 0 1 theme protein 90:96 arg1 inhibitors 98:107 potent cholesterol ester transfer protein inhibitors 56:107 potent cholesterol ester transfer protein inhibitors 56:107 Discovery of hydroxyl 1,2-diphenylethanamine analogs as potent cholesterol ester transfer protein inhibitors. 27256912 2 2 theme DPPE 390:393 arg1 series 396:401 the previously disclosed DiPhenylPyridineEthanamine (DPPE) series 337:401 the previously disclosed DiPhenylPyridineEthanamine (DPPE) series 337:401 In an effort to improve the pharmaceutical properties in the previously disclosed DiPhenylPyridineEthanamine (DPPE) series, polar groups were introduced to the N-linked quaternary center. 27256912 3 3 theme lead 572:575 arg1 compound 577:584 lead compound 16 572:587 lead compound 16 572:587 Optimization of analogues for potency, in vitro liability profile and efficacy led to identification of lead compound 16 which demonstrated robust pharmacodynamic effects in human CETP/apo-B100 dual transgenic mice. 27256912 2 4 theme pharmaceutical 308:321 arg1 properties 323:332 the pharmaceutical properties 304:332 the pharmaceutical properties in the previously disclosed DiPhenylPyridineEthanamine (DPPE) series 304:401 In an effort to improve the pharmaceutical properties in the previously disclosed DiPhenylPyridineEthanamine (DPPE) series, polar groups were introduced to the N-linked quaternary center. 27256912 3 5 theme compound 577:584 arg1 identification 554:567 identification 554:567 identification of lead compound 16 which demonstrated robust pharmacodynamic effects in human CETP/apo-B100 dual transgenic mice 554:681 Optimization of analogues for potency, in vitro liability profile and efficacy led to identification of lead compound 16 which demonstrated robust pharmacodynamic effects in human CETP/apo-B100 dual transgenic mice. 27256912 1 6 theme transfer 208:215 arg1 target 247:252 a therapeutic target 233:252 a therapeutic target to raise HDL cholesterol 233:277 Hydroxyl 1,2-diphenylethanamine analogs were identified as potent inhibitors of cholesterol ester transfer protein (CETP), a therapeutic target to raise HDL cholesterol. 27256912 1 6 theme transfer 208:215 arg1 CETP 226:229 CETP 226:229 CETP 226:229 Hydroxyl 1,2-diphenylethanamine analogs were identified as potent inhibitors of cholesterol ester transfer protein (CETP), a therapeutic target to raise HDL cholesterol. 27256912 1 6 theme transfer 208:215 arg1 protein 217:223 cholesterol ester transfer protein 190:223 cholesterol ester transfer protein (CETP) 190:230 Hydroxyl 1,2-diphenylethanamine analogs were identified as potent inhibitors of cholesterol ester transfer protein (CETP), a therapeutic target to raise HDL cholesterol. 27256912 1 7 theme protein 217:223 arg1 inhibitors 176:185 potent inhibitors 169:185 potent inhibitors of cholesterol ester transfer protein (CETP), a therapeutic target to raise HDL cholesterol 169:277 Hydroxyl 1,2-diphenylethanamine analogs were identified as potent inhibitors of cholesterol ester transfer protein (CETP), a therapeutic target to raise HDL cholesterol. 27256912 1 7 theme protein 217:223 arg1 analogs 142:148 Hydroxyl 1,2-diphenylethanamine analogs 110:148 Hydroxyl 1,2-diphenylethanamine analogs 110:148 Hydroxyl 1,2-diphenylethanamine analogs were identified as potent inhibitors of cholesterol ester transfer protein (CETP), a therapeutic target to raise HDL cholesterol. 27256912 1 8 theme Hydroxyl 110:117 arg1 inhibitors 176:185 potent inhibitors 169:185 potent inhibitors of cholesterol ester transfer protein (CETP), a therapeutic target to raise HDL cholesterol 169:277 Hydroxyl 1,2-diphenylethanamine analogs were identified as potent inhibitors of cholesterol ester transfer protein (CETP), a therapeutic target to raise HDL cholesterol. 27256912 1 8 theme Hydroxyl 110:117 arg1 analogs 142:148 Hydroxyl 1,2-diphenylethanamine analogs 110:148 Hydroxyl 1,2-diphenylethanamine analogs 110:148 Hydroxyl 1,2-diphenylethanamine analogs were identified as potent inhibitors of cholesterol ester transfer protein (CETP), a therapeutic target to raise HDL cholesterol. 27256912 2 9 theme polar 404:408 arg1 groups 410:415 polar groups 404:415 polar groups 404:415 In an effort to improve the pharmaceutical properties in the previously disclosed DiPhenylPyridineEthanamine (DPPE) series, polar groups were introduced to the N-linked quaternary center. 27256912 0 10 theme 1,2-diphenylethanamine 22:43 arg1 analogs 45:51 hydroxyl 1,2-diphenylethanamine analogs 13:51 hydroxyl 1,2-diphenylethanamine analogs 13:51 Discovery of hydroxyl 1,2-diphenylethanamine analogs as potent cholesterol ester transfer protein inhibitors. 27256912 1 11 theme 1,2-diphenylethanamine 119:140 arg1 inhibitors 176:185 potent inhibitors 169:185 potent inhibitors of cholesterol ester transfer protein (CETP), a therapeutic target to raise HDL cholesterol 169:277 Hydroxyl 1,2-diphenylethanamine analogs were identified as potent inhibitors of cholesterol ester transfer protein (CETP), a therapeutic target to raise HDL cholesterol. 27256912 1 11 theme 1,2-diphenylethanamine 119:140 arg1 analogs 142:148 Hydroxyl 1,2-diphenylethanamine analogs 110:148 Hydroxyl 1,2-diphenylethanamine analogs 110:148 Hydroxyl 1,2-diphenylethanamine analogs were identified as potent inhibitors of cholesterol ester transfer protein (CETP), a therapeutic target to raise HDL cholesterol. 27256912 2 12 theme quaternary 449:458 arg1 center 460:465 the N-linked quaternary center 436:465 the N-linked quaternary center 436:465 In an effort to improve the pharmaceutical properties in the previously disclosed DiPhenylPyridineEthanamine (DPPE) series, polar groups were introduced to the N-linked quaternary center. 27256912 0 13 theme hydroxyl 13:20 arg1 analogs 45:51 hydroxyl 1,2-diphenylethanamine analogs 13:51 hydroxyl 1,2-diphenylethanamine analogs 13:51 Discovery of hydroxyl 1,2-diphenylethanamine analogs as potent cholesterol ester transfer protein inhibitors. 27256912 1 14 theme ester 202:206 arg1 target 247:252 a therapeutic target 233:252 a therapeutic target to raise HDL cholesterol 233:277 Hydroxyl 1,2-diphenylethanamine analogs were identified as potent inhibitors of cholesterol ester transfer protein (CETP), a therapeutic target to raise HDL cholesterol. 27256912 1 14 theme ester 202:206 arg1 CETP 226:229 CETP 226:229 CETP 226:229 Hydroxyl 1,2-diphenylethanamine analogs were identified as potent inhibitors of cholesterol ester transfer protein (CETP), a therapeutic target to raise HDL cholesterol. 27256912 1 14 theme ester 202:206 arg1 protein 217:223 cholesterol ester transfer protein 190:223 cholesterol ester transfer protein (CETP) 190:230 Hydroxyl 1,2-diphenylethanamine analogs were identified as potent inhibitors of cholesterol ester transfer protein (CETP), a therapeutic target to raise HDL cholesterol. 27256912 2 15 theme N-linked 440:447 arg1 center 460:465 the N-linked quaternary center 436:465 the N-linked quaternary center 436:465 In an effort to improve the pharmaceutical properties in the previously disclosed DiPhenylPyridineEthanamine (DPPE) series, polar groups were introduced to the N-linked quaternary center. 27256912 3 16 theme analogues 484:492 arg1 Optimization 468:479 Optimization 468:479 Optimization of analogues for potency, in vitro liability profile and efficacy 468:545 Optimization of analogues for potency, in vitro liability profile and efficacy led to identification of lead compound 16 which demonstrated robust pharmacodynamic effects in human CETP/apo-B100 dual transgenic mice. 27256912 0 17 theme analogs 45:51 arg1 Discovery 0:8 Discovery 0:8 Discovery of hydroxyl 1,2-diphenylethanamine analogs as potent cholesterol ester transfer protein inhibitors. 0:108 Discovery of hydroxyl 1,2-diphenylethanamine analogs as potent cholesterol ester transfer protein inhibitors. 27256912 1 18 dep target 247:252 arg1 raise 257:261 raise 257:261 to raise HDL cholesterol 254:277 Hydroxyl 1,2-diphenylethanamine analogs were identified as potent inhibitors of cholesterol ester transfer protein (CETP), a therapeutic target to raise HDL cholesterol. 27256912 3 19 theme human 642:646 arg1 mice 678:681 human CETP/apo-B100 dual transgenic mice 642:681 human CETP/apo-B100 dual transgenic mice 642:681 Optimization of analogues for potency, in vitro liability profile and efficacy led to identification of lead compound 16 which demonstrated robust pharmacodynamic effects in human CETP/apo-B100 dual transgenic mice. 27256912 1 20 theme therapeutic 235:245 arg1 target 247:252 a therapeutic target 233:252 a therapeutic target to raise HDL cholesterol 233:277 Hydroxyl 1,2-diphenylethanamine analogs were identified as potent inhibitors of cholesterol ester transfer protein (CETP), a therapeutic target to raise HDL cholesterol. 27256912 1 20 theme therapeutic 235:245 arg1 protein 217:223 cholesterol ester transfer protein 190:223 cholesterol ester transfer protein (CETP) 190:230 Hydroxyl 1,2-diphenylethanamine analogs were identified as potent inhibitors of cholesterol ester transfer protein (CETP), a therapeutic target to raise HDL cholesterol. 27256912 0 21 theme cholesterol 63:73 arg1 inhibitors 98:107 potent cholesterol ester transfer protein inhibitors 56:107 potent cholesterol ester transfer protein inhibitors 56:107 Discovery of hydroxyl 1,2-diphenylethanamine analogs as potent cholesterol ester transfer protein inhibitors. 27256912 3 22 theme pharmacodynamic 615:629 arg1 effects 631:637 robust pharmacodynamic effects 608:637 robust pharmacodynamic effects 608:637 Optimization of analogues for potency, in vitro liability profile and efficacy led to identification of lead compound 16 which demonstrated robust pharmacodynamic effects in human CETP/apo-B100 dual transgenic mice. 27256912 3 23 theme liability 516:524 arg1 profile 526:532 in vitro liability profile 507:532 in vitro liability profile 507:532 Optimization of analogues for potency, in vitro liability profile and efficacy led to identification of lead compound 16 which demonstrated robust pharmacodynamic effects in human CETP/apo-B100 dual transgenic mice. 27256912 0 24 theme potent 56:61 arg1 inhibitors 98:107 potent cholesterol ester transfer protein inhibitors 56:107 potent cholesterol ester transfer protein inhibitors 56:107 Discovery of hydroxyl 1,2-diphenylethanamine analogs as potent cholesterol ester transfer protein inhibitors. 27256912 2 25 theme DiPhenylPyridineEthanamine 362:387 arg1 series 396:401 the previously disclosed DiPhenylPyridineEthanamine (DPPE) series 337:401 the previously disclosed DiPhenylPyridineEthanamine (DPPE) series 337:401 In an effort to improve the pharmaceutical properties in the previously disclosed DiPhenylPyridineEthanamine (DPPE) series, polar groups were introduced to the N-linked quaternary center. 27256912 3 26 theme transgenic 667:676 arg1 mice 678:681 human CETP/apo-B100 dual transgenic mice 642:681 human CETP/apo-B100 dual transgenic mice 642:681 Optimization of analogues for potency, in vitro liability profile and efficacy led to identification of lead compound 16 which demonstrated robust pharmacodynamic effects in human CETP/apo-B100 dual transgenic mice. 27256912 2 27 theme disclosed 352:360 arg1 series 396:401 the previously disclosed DiPhenylPyridineEthanamine (DPPE) series 337:401 the previously disclosed DiPhenylPyridineEthanamine (DPPE) series 337:401 In an effort to improve the pharmaceutical properties in the previously disclosed DiPhenylPyridineEthanamine (DPPE) series, polar groups were introduced to the N-linked quaternary center. 27256912 3 28 dep in 507:508 arg1 vitro 510:514 vitro 510:514 vitro 510:514 Optimization of analogues for potency, in vitro liability profile and efficacy led to identification of lead compound 16 which demonstrated robust pharmacodynamic effects in human CETP/apo-B100 dual transgenic mice. 27256912 1 29 theme potent 169:174 arg1 inhibitors 176:185 potent inhibitors 169:185 potent inhibitors of cholesterol ester transfer protein (CETP), a therapeutic target to raise HDL cholesterol 169:277 Hydroxyl 1,2-diphenylethanamine analogs were identified as potent inhibitors of cholesterol ester transfer protein (CETP), a therapeutic target to raise HDL cholesterol. 27256912 1 29 theme potent 169:174 arg1 analogs 142:148 Hydroxyl 1,2-diphenylethanamine analogs 110:148 Hydroxyl 1,2-diphenylethanamine analogs 110:148 Hydroxyl 1,2-diphenylethanamine analogs were identified as potent inhibitors of cholesterol ester transfer protein (CETP), a therapeutic target to raise HDL cholesterol. 27256912 3 30 theme in 507:508 arg1 profile 526:532 in vitro liability profile 507:532 in vitro liability profile 507:532 Optimization of analogues for potency, in vitro liability profile and efficacy led to identification of lead compound 16 which demonstrated robust pharmacodynamic effects in human CETP/apo-B100 dual transgenic mice. 27256912 0 31 theme transfer 81:88 arg1 inhibitors 98:107 potent cholesterol ester transfer protein inhibitors 56:107 potent cholesterol ester transfer protein inhibitors 56:107 Discovery of hydroxyl 1,2-diphenylethanamine analogs as potent cholesterol ester transfer protein inhibitors. 27256912 2 32 link N-linked 440:447 arg1 center 460:465 the N-linked quaternary center 436:465 the N-linked quaternary center 436:465 In an effort to improve the pharmaceutical properties in the previously disclosed DiPhenylPyridineEthanamine (DPPE) series, polar groups were introduced to the N-linked quaternary center. 27256912 3 33 theme CETP/apo-B100 648:660 arg1 mice 678:681 human CETP/apo-B100 dual transgenic mice 642:681 human CETP/apo-B100 dual transgenic mice 642:681 Optimization of analogues for potency, in vitro liability profile and efficacy led to identification of lead compound 16 which demonstrated robust pharmacodynamic effects in human CETP/apo-B100 dual transgenic mice. 27256912 0 34 theme ester 75:79 arg1 inhibitors 98:107 potent cholesterol ester transfer protein inhibitors 56:107 potent cholesterol ester transfer protein inhibitors 56:107 Discovery of hydroxyl 1,2-diphenylethanamine analogs as potent cholesterol ester transfer protein inhibitors. 27256912 3 35 theme dual 662:665 arg1 mice 678:681 human CETP/apo-B100 dual transgenic mice 642:681 human CETP/apo-B100 dual transgenic mice 642:681 Optimization of analogues for potency, in vitro liability profile and efficacy led to identification of lead compound 16 which demonstrated robust pharmacodynamic effects in human CETP/apo-B100 dual transgenic mice. 27256912 3 36 theme robust 608:613 arg1 effects 631:637 robust pharmacodynamic effects 608:637 robust pharmacodynamic effects 608:637 Optimization of analogues for potency, in vitro liability profile and efficacy led to identification of lead compound 16 which demonstrated robust pharmacodynamic effects in human CETP/apo-B100 dual transgenic mice. 27256912 2 37 from properties 323:332 arg1 series 396:401 the previously disclosed DiPhenylPyridineEthanamine (DPPE) series 337:401 the previously disclosed DiPhenylPyridineEthanamine (DPPE) series 337:401 In an effort to improve the pharmaceutical properties in the previously disclosed DiPhenylPyridineEthanamine (DPPE) series, polar groups were introduced to the N-linked quaternary center. 27256912 1 38 theme HDL 263:265 arg1 cholesterol 267:277 HDL cholesterol 263:277 HDL cholesterol 263:277 Hydroxyl 1,2-diphenylethanamine analogs were identified as potent inhibitors of cholesterol ester transfer protein (CETP), a therapeutic target to raise HDL cholesterol. 27050086 0 0 theme δ- 57:58 arg1 acids 72:76 δ- and γ-amino acids 57:76 δ- and γ-amino acids 57:76 One-pot, regiospecific assembly of (E)-benzamidines from δ- and γ-amino acids via an intramolecular aminoquinazolinone rearrangement. 27050086 3 1 theme high 620:623 arg1 yield 625:629 high yield 620:629 high yield 620:629 The transformation was extensively optimized in terms of reaction conditions and scope, resulting in a protocol that consistently affords diversely functionalized amidines in high yield. 27050086 0 2 theme γ-amino 64:70 arg1 acids 72:76 δ- and γ-amino acids 57:76 δ- and γ-amino acids 57:76 One-pot, regiospecific assembly of (E)-benzamidines from δ- and γ-amino acids via an intramolecular aminoquinazolinone rearrangement. 27050086 2 3 theme reaction 300:307 arg1 parameters 309:318 reaction parameters 300:318 reaction parameters including the effect of changing solvent and temperature, as well as varying electronic substituents on the structural core 300:442 This methodology study explored reaction parameters including the effect of changing solvent and temperature, as well as varying electronic substituents on the structural core. 27050086 2 3 theme reaction 300:307 arg1 effect 334:339 the effect 330:339 the effect of changing solvent and temperature, as well as varying electronic substituents on the structural core 330:442 This methodology study explored reaction parameters including the effect of changing solvent and temperature, as well as varying electronic substituents on the structural core. 27050086 4 4 theme δ-amino 900:906 arg1 acids 908:912 δ-amino acids 900:912 δ-amino acids 900:912 The process permits regional structural derivatization that was previously inaccessible, and the multistep process was also reduced to a telescoped, five-step sequence that efficiently affords pharmacologically unique (E)-benzamidoamidines from N-BOC protected γ- and δ-amino acids. 27050086 4 5 theme unique 843:848 arg1 -benzamidoamidines 853:870 pharmacologically unique (E)-benzamidoamidines 825:870 pharmacologically unique (E)-benzamidoamidines 825:870 The process permits regional structural derivatization that was previously inaccessible, and the multistep process was also reduced to a telescoped, five-step sequence that efficiently affords pharmacologically unique (E)-benzamidoamidines from N-BOC protected γ- and δ-amino acids. 27050086 4 5 theme unique 843:848 arg1 E 851:851 E 851:851 E 851:851 The process permits regional structural derivatization that was previously inaccessible, and the multistep process was also reduced to a telescoped, five-step sequence that efficiently affords pharmacologically unique (E)-benzamidoamidines from N-BOC protected γ- and δ-amino acids. 27050086 1 6 theme novel 162:166 arg1 benzamidines 178:189 novel, N-linked benzamidines 162:189 novel, N-linked benzamidines resulting from a regiospecific rearrangement of quinazolinones 162:252 The efficient generation of novel, N-linked benzamidines resulting from a regiospecific rearrangement of quinazolinones is described. 27050086 4 7 dep telescoped 769:778 arg1 five-step 781:789 five-step 781:789 five-step 781:789 The process permits regional structural derivatization that was previously inaccessible, and the multistep process was also reduced to a telescoped, five-step sequence that efficiently affords pharmacologically unique (E)-benzamidoamidines from N-BOC protected γ- and δ-amino acids. 27050086 2 8 theme electronic 397:406 arg1 substituents 408:419 electronic substituents 397:419 electronic substituents on the structural core 397:442 This methodology study explored reaction parameters including the effect of changing solvent and temperature, as well as varying electronic substituents on the structural core. 27050086 0 9 theme One-pot 0:6 arg1 assembly 23:30 One-pot, regiospecific assembly 0:30 One-pot, regiospecific assembly of (E) 0:37 One-pot, regiospecific assembly of (E)-benzamidines from δ- and γ-amino acids via an intramolecular aminoquinazolinone rearrangement. 27050086 1 10 theme benzamidines 178:189 arg1 generation 148:157 The efficient generation 134:157 The efficient generation of novel, N-linked benzamidines resulting from a regiospecific rearrangement of quinazolinones 134:252 The efficient generation of novel, N-linked benzamidines resulting from a regiospecific rearrangement of quinazolinones is described. 27050086 0 11 theme aminoquinazolinone 100:117 arg1 rearrangement 119:131 an intramolecular aminoquinazolinone rearrangement 82:131 an intramolecular aminoquinazolinone rearrangement 82:131 One-pot, regiospecific assembly of (E)-benzamidines from δ- and γ-amino acids via an intramolecular aminoquinazolinone rearrangement. 27050086 0 12 theme intramolecular 85:98 arg1 rearrangement 119:131 an intramolecular aminoquinazolinone rearrangement 82:131 an intramolecular aminoquinazolinone rearrangement 82:131 One-pot, regiospecific assembly of (E)-benzamidines from δ- and γ-amino acids via an intramolecular aminoquinazolinone rearrangement. 27050086 3 13 theme functionalized 593:606 arg1 amidines 608:615 diversely functionalized amidines 583:615 diversely functionalized amidines in high yield 583:629 The transformation was extensively optimized in terms of reaction conditions and scope, resulting in a protocol that consistently affords diversely functionalized amidines in high yield. 27050086 4 14 theme N-BOC 877:881 arg1 γ- 893:894 N-BOC protected γ- 877:894 N-BOC protected γ- 877:894 The process permits regional structural derivatization that was previously inaccessible, and the multistep process was also reduced to a telescoped, five-step sequence that efficiently affords pharmacologically unique (E)-benzamidoamidines from N-BOC protected γ- and δ-amino acids. 27050086 2 15 theme structural 428:437 arg1 core 439:442 the structural core 424:442 the structural core 424:442 This methodology study explored reaction parameters including the effect of changing solvent and temperature, as well as varying electronic substituents on the structural core. 27050086 4 16 theme structural 661:670 arg1 derivatization 672:685 regional structural derivatization 652:685 regional structural derivatization that was previously inaccessible 652:718 The process permits regional structural derivatization that was previously inaccessible, and the multistep process was also reduced to a telescoped, five-step sequence that efficiently affords pharmacologically unique (E)-benzamidoamidines from N-BOC protected γ- and δ-amino acids. 27050086 1 17 theme regiospecific 208:220 arg1 rearrangement 222:234 a regiospecific rearrangement 206:234 a regiospecific rearrangement of quinazolinones 206:252 The efficient generation of novel, N-linked benzamidines resulting from a regiospecific rearrangement of quinazolinones is described. 27050086 1 18 dep novel 162:166 arg1 N-linked 169:176 N-linked 169:176 N-linked 169:176 The efficient generation of novel, N-linked benzamidines resulting from a regiospecific rearrangement of quinazolinones is described. 27050086 0 19 theme E 36:36 arg1 assembly 23:30 One-pot, regiospecific assembly 0:30 One-pot, regiospecific assembly of (E) 0:37 One-pot, regiospecific assembly of (E)-benzamidines from δ- and γ-amino acids via an intramolecular aminoquinazolinone rearrangement. 27050086 4 20 theme protected 883:891 arg1 γ- 893:894 N-BOC protected γ- 877:894 N-BOC protected γ- 877:894 The process permits regional structural derivatization that was previously inaccessible, and the multistep process was also reduced to a telescoped, five-step sequence that efficiently affords pharmacologically unique (E)-benzamidoamidines from N-BOC protected γ- and δ-amino acids. 27050086 3 21 theme scope 526:530 arg1 terms 493:497 terms 493:497 terms of reaction conditions and scope 493:530 The transformation was extensively optimized in terms of reaction conditions and scope, resulting in a protocol that consistently affords diversely functionalized amidines in high yield. 27050086 2 22 theme methodology 273:283 arg1 study 285:289 This methodology study 268:289 This methodology study 268:289 This methodology study explored reaction parameters including the effect of changing solvent and temperature, as well as varying electronic substituents on the structural core. 27050086 2 23 from substituents 408:419 arg1 core 439:442 the structural core 424:442 the structural core 424:442 This methodology study explored reaction parameters including the effect of changing solvent and temperature, as well as varying electronic substituents on the structural core. 27050086 3 24 theme reaction 502:509 arg1 conditions 511:520 reaction conditions 502:520 reaction conditions 502:520 The transformation was extensively optimized in terms of reaction conditions and scope, resulting in a protocol that consistently affords diversely functionalized amidines in high yield. 27050086 3 25 theme conditions 511:520 arg1 terms 493:497 terms 493:497 terms of reaction conditions and scope 493:530 The transformation was extensively optimized in terms of reaction conditions and scope, resulting in a protocol that consistently affords diversely functionalized amidines in high yield. 27050086 3 26 from amidines 608:615 arg1 yield 625:629 high yield 620:629 high yield 620:629 The transformation was extensively optimized in terms of reaction conditions and scope, resulting in a protocol that consistently affords diversely functionalized amidines in high yield. 27050086 4 27 theme telescoped 769:778 arg1 sequence 791:798 a telescoped, five-step sequence 767:798 a telescoped, five-step sequence that efficiently affords pharmacologically unique (E)-benzamidoamidines from N-BOC protected γ- and δ-amino acids 767:912 The process permits regional structural derivatization that was previously inaccessible, and the multistep process was also reduced to a telescoped, five-step sequence that efficiently affords pharmacologically unique (E)-benzamidoamidines from N-BOC protected γ- and δ-amino acids. 27050086 4 28 theme multistep 729:737 arg1 process 739:745 the multistep process 725:745 the multistep process 725:745 The process permits regional structural derivatization that was previously inaccessible, and the multistep process was also reduced to a telescoped, five-step sequence that efficiently affords pharmacologically unique (E)-benzamidoamidines from N-BOC protected γ- and δ-amino acids. 27050086 1 29 theme quinazolinones 239:252 arg1 rearrangement 222:234 a regiospecific rearrangement 206:234 a regiospecific rearrangement of quinazolinones 206:252 The efficient generation of novel, N-linked benzamidines resulting from a regiospecific rearrangement of quinazolinones is described. 27050086 0 30 dep One-pot 0:6 arg1 regiospecific 9:21 regiospecific 9:21 regiospecific 9:21 One-pot, regiospecific assembly of (E)-benzamidines from δ- and γ-amino acids via an intramolecular aminoquinazolinone rearrangement. 27050086 1 31 theme efficient 138:146 arg1 generation 148:157 The efficient generation 134:157 The efficient generation of novel, N-linked benzamidines resulting from a regiospecific rearrangement of quinazolinones 134:252 The efficient generation of novel, N-linked benzamidines resulting from a regiospecific rearrangement of quinazolinones is described. 27050086 4 32 theme regional 652:659 arg1 derivatization 672:685 regional structural derivatization 652:685 regional structural derivatization that was previously inaccessible 652:718 The process permits regional structural derivatization that was previously inaccessible, and the multistep process was also reduced to a telescoped, five-step sequence that efficiently affords pharmacologically unique (E)-benzamidoamidines from N-BOC protected γ- and δ-amino acids. 24934233 3 0 dep 4.70 485:488 arg1 showed 511:516 showed 511:516 showed that BmN-SFM cells were easily susceptible to B. mori nucleopolyhedrovirus (BmNPV), and both the multiplication of budded virus and the promoter activity of the polyhedrin gene in BmN-SFM cells were almost the same as those in BmN4 cells before adaptation 511:772 The BmN-SFM was subcultured 200 times, and the population doubling time was 4.70 d. Infection studies showed that BmN-SFM cells were easily susceptible to B. mori nucleopolyhedrovirus (BmNPV), and both the multiplication of budded virus and the promoter activity of the polyhedrin gene in BmN-SFM cells were almost the same as those in BmN4 cells before adaptation. 24934233 5 1 theme expression 1007:1016 arg1 system 1025:1030 a BmNPV-based baculovirus expression vector system 981:1030 a BmNPV-based baculovirus expression vector system with serum-free conditions 981:1057 These findings indicate that BmN-SFM is particularly useful for a BmNPV-based baculovirus expression vector system with serum-free conditions. 24934233 4 2 mod modified 868:875 arg1 interleukin-3 795:807 mouse interleukin-3 789:807 mouse interleukin-3 expressed by a recombinant BmNPV 789:840 Additionally, mouse interleukin-3 expressed by a recombinant BmNPV was normally secreted and modified with N-linked glycans in BmN-SFM cells. 24934233 4 2 mod modified 868:875 arg3 glycans 891:897 N-linked glycans 882:897 N-linked glycans in BmN-SFM cells 882:914 Additionally, mouse interleukin-3 expressed by a recombinant BmNPV was normally secreted and modified with N-linked glycans in BmN-SFM cells. 24934233 4 3 theme N-linked 882:889 arg1 glycans 891:897 N-linked glycans 882:897 N-linked glycans in BmN-SFM cells 882:914 Additionally, mouse interleukin-3 expressed by a recombinant BmNPV was normally secreted and modified with N-linked glycans in BmN-SFM cells. 24934233 2 4 theme BmN4 295:298 arg1 cells 300:304 The BmN4 cells 291:304 The BmN4 cells 291:304 The BmN4 cells adapted to the SFM (BmN-SFM) adhered strongly to the culture flask and showed altered cell morphology. 24934233 3 5 theme population 456:465 arg1 4.70 485:488 4.70 485:488 4.70 485:488 The BmN-SFM was subcultured 200 times, and the population doubling time was 4.70 d. Infection studies showed that BmN-SFM cells were easily susceptible to B. mori nucleopolyhedrovirus (BmNPV), and both the multiplication of budded virus and the promoter activity of the polyhedrin gene in BmN-SFM cells were almost the same as those in BmN4 cells before adaptation. 24934233 3 5 theme population 456:465 arg1 time 476:479 the population doubling time 452:479 the population doubling time 452:479 The BmN-SFM was subcultured 200 times, and the population doubling time was 4.70 d. Infection studies showed that BmN-SFM cells were easily susceptible to B. mori nucleopolyhedrovirus (BmNPV), and both the multiplication of budded virus and the promoter activity of the polyhedrin gene in BmN-SFM cells were almost the same as those in BmN4 cells before adaptation. 24934233 1 6 theme serum-containing 230:245 arg1 medium 254:259 the serum-containing TC-100 medium 226:259 the serum-containing TC-100 medium content 226:267 Bombyx mori ovary-derived BmN4 cells have been successfully adapted to a commercial serum-free medium (SFM; SF900-II) by gradually reducing the serum-containing TC-100 medium content from 100 to 0% (v/v). 24934233 0 7 theme serum-free 66:75 arg1 culture 77:83 serum-free culture 66:83 serum-free culture 66:83 Long-term adaptation of the Bombyx mori BmN4 cell line to grow in serum-free culture. 24934233 3 8 theme budded 633:638 arg1 virus 640:644 budded virus 633:644 budded virus 633:644 The BmN-SFM was subcultured 200 times, and the population doubling time was 4.70 d. Infection studies showed that BmN-SFM cells were easily susceptible to B. mori nucleopolyhedrovirus (BmNPV), and both the multiplication of budded virus and the promoter activity of the polyhedrin gene in BmN-SFM cells were almost the same as those in BmN4 cells before adaptation. 24934233 3 9 theme doubling 467:474 arg1 4.70 485:488 4.70 485:488 4.70 485:488 The BmN-SFM was subcultured 200 times, and the population doubling time was 4.70 d. Infection studies showed that BmN-SFM cells were easily susceptible to B. mori nucleopolyhedrovirus (BmNPV), and both the multiplication of budded virus and the promoter activity of the polyhedrin gene in BmN-SFM cells were almost the same as those in BmN4 cells before adaptation. 24934233 3 9 theme doubling 467:474 arg1 time 476:479 the population doubling time 452:479 the population doubling time 452:479 The BmN-SFM was subcultured 200 times, and the population doubling time was 4.70 d. Infection studies showed that BmN-SFM cells were easily susceptible to B. mori nucleopolyhedrovirus (BmNPV), and both the multiplication of budded virus and the promoter activity of the polyhedrin gene in BmN-SFM cells were almost the same as those in BmN4 cells before adaptation. 24934233 1 10 theme TC-100 247:252 arg1 medium 254:259 the serum-containing TC-100 medium 226:259 the serum-containing TC-100 medium content 226:267 Bombyx mori ovary-derived BmN4 cells have been successfully adapted to a commercial serum-free medium (SFM; SF900-II) by gradually reducing the serum-containing TC-100 medium content from 100 to 0% (v/v). 24934233 3 11 theme virus 640:644 arg1 activity 663:670 the promoter activity 650:670 the promoter activity of the polyhedrin gene in BmN-SFM cells 650:710 The BmN-SFM was subcultured 200 times, and the population doubling time was 4.70 d. Infection studies showed that BmN-SFM cells were easily susceptible to B. mori nucleopolyhedrovirus (BmNPV), and both the multiplication of budded virus and the promoter activity of the polyhedrin gene in BmN-SFM cells were almost the same as those in BmN4 cells before adaptation. 24934233 3 11 theme virus 640:644 arg1 same 728:731 same 728:731 same 728:731 The BmN-SFM was subcultured 200 times, and the population doubling time was 4.70 d. Infection studies showed that BmN-SFM cells were easily susceptible to B. mori nucleopolyhedrovirus (BmNPV), and both the multiplication of budded virus and the promoter activity of the polyhedrin gene in BmN-SFM cells were almost the same as those in BmN4 cells before adaptation. 24934233 3 11 theme virus 640:644 arg1 multiplication 615:628 the multiplication 611:628 the multiplication of budded virus 611:644 The BmN-SFM was subcultured 200 times, and the population doubling time was 4.70 d. Infection studies showed that BmN-SFM cells were easily susceptible to B. mori nucleopolyhedrovirus (BmNPV), and both the multiplication of budded virus and the promoter activity of the polyhedrin gene in BmN-SFM cells were almost the same as those in BmN4 cells before adaptation. 24934233 4 12 theme BmN-SFM 902:908 arg1 cells 910:914 BmN-SFM cells 902:914 BmN-SFM cells 902:914 Additionally, mouse interleukin-3 expressed by a recombinant BmNPV was normally secreted and modified with N-linked glycans in BmN-SFM cells. 24934233 3 13 from multiplication 615:628 arg1 cells 706:710 BmN-SFM cells 698:710 BmN-SFM cells 698:710 The BmN-SFM was subcultured 200 times, and the population doubling time was 4.70 d. Infection studies showed that BmN-SFM cells were easily susceptible to B. mori nucleopolyhedrovirus (BmNPV), and both the multiplication of budded virus and the promoter activity of the polyhedrin gene in BmN-SFM cells were almost the same as those in BmN4 cells before adaptation. 24934233 1 14 dep 0 281:281 arg1 to 278:279 to 278:279 to 278:279 Bombyx mori ovary-derived BmN4 cells have been successfully adapted to a commercial serum-free medium (SFM; SF900-II) by gradually reducing the serum-containing TC-100 medium content from 100 to 0% (v/v). 24934233 3 15 theme promoter 654:661 arg1 activity 663:670 the promoter activity 650:670 the promoter activity of the polyhedrin gene in BmN-SFM cells 650:710 The BmN-SFM was subcultured 200 times, and the population doubling time was 4.70 d. Infection studies showed that BmN-SFM cells were easily susceptible to B. mori nucleopolyhedrovirus (BmNPV), and both the multiplication of budded virus and the promoter activity of the polyhedrin gene in BmN-SFM cells were almost the same as those in BmN4 cells before adaptation. 24934233 3 15 theme promoter 654:661 arg1 same 728:731 same 728:731 same 728:731 The BmN-SFM was subcultured 200 times, and the population doubling time was 4.70 d. Infection studies showed that BmN-SFM cells were easily susceptible to B. mori nucleopolyhedrovirus (BmNPV), and both the multiplication of budded virus and the promoter activity of the polyhedrin gene in BmN-SFM cells were almost the same as those in BmN4 cells before adaptation. 24934233 3 15 theme promoter 654:661 arg1 multiplication 615:628 the multiplication 611:628 the multiplication of budded virus 611:644 The BmN-SFM was subcultured 200 times, and the population doubling time was 4.70 d. Infection studies showed that BmN-SFM cells were easily susceptible to B. mori nucleopolyhedrovirus (BmNPV), and both the multiplication of budded virus and the promoter activity of the polyhedrin gene in BmN-SFM cells were almost the same as those in BmN4 cells before adaptation. 24934233 5 16 theme vector 1018:1023 arg1 system 1025:1030 a BmNPV-based baculovirus expression vector system 981:1030 a BmNPV-based baculovirus expression vector system with serum-free conditions 981:1057 These findings indicate that BmN-SFM is particularly useful for a BmNPV-based baculovirus expression vector system with serum-free conditions. 24934233 1 17 theme commercial 159:168 arg1 SFM 189:191 SFM 189:191 SFM; SF900-II 189:201 Bombyx mori ovary-derived BmN4 cells have been successfully adapted to a commercial serum-free medium (SFM; SF900-II) by gradually reducing the serum-containing TC-100 medium content from 100 to 0% (v/v). 24934233 1 17 theme commercial 159:168 arg1 medium 181:186 a commercial serum-free medium 157:186 a commercial serum-free medium (SFM; SF900-II) 157:202 Bombyx mori ovary-derived BmN4 cells have been successfully adapted to a commercial serum-free medium (SFM; SF900-II) by gradually reducing the serum-containing TC-100 medium content from 100 to 0% (v/v). 24934233 0 18 theme Long-term 0:8 arg1 adaptation 10:19 Long-term adaptation 0:19 Long-term adaptation of the Bombyx mori BmN4 cell line 0:53 Long-term adaptation of the Bombyx mori BmN4 cell line to grow in serum-free culture. 24934233 1 19 theme medium 254:259 arg1 content 261:267 the serum-containing TC-100 medium content 226:267 the serum-containing TC-100 medium content 226:267 Bombyx mori ovary-derived BmN4 cells have been successfully adapted to a commercial serum-free medium (SFM; SF900-II) by gradually reducing the serum-containing TC-100 medium content from 100 to 0% (v/v). 24934233 3 20 from activity 663:670 arg1 cells 706:710 BmN-SFM cells 698:710 BmN-SFM cells 698:710 The BmN-SFM was subcultured 200 times, and the population doubling time was 4.70 d. Infection studies showed that BmN-SFM cells were easily susceptible to B. mori nucleopolyhedrovirus (BmNPV), and both the multiplication of budded virus and the promoter activity of the polyhedrin gene in BmN-SFM cells were almost the same as those in BmN4 cells before adaptation. 24934233 3 21 theme d. 490:491 arg1 studies 503:509 d. Infection studies 490:509 d. Infection studies 490:509 The BmN-SFM was subcultured 200 times, and the population doubling time was 4.70 d. Infection studies showed that BmN-SFM cells were easily susceptible to B. mori nucleopolyhedrovirus (BmNPV), and both the multiplication of budded virus and the promoter activity of the polyhedrin gene in BmN-SFM cells were almost the same as those in BmN4 cells before adaptation. 24934233 1 22 theme serum-free 170:179 arg1 SFM 189:191 SFM 189:191 SFM; SF900-II 189:201 Bombyx mori ovary-derived BmN4 cells have been successfully adapted to a commercial serum-free medium (SFM; SF900-II) by gradually reducing the serum-containing TC-100 medium content from 100 to 0% (v/v). 24934233 1 22 theme serum-free 170:179 arg1 medium 181:186 a commercial serum-free medium 157:186 a commercial serum-free medium (SFM; SF900-II) 157:202 Bombyx mori ovary-derived BmN4 cells have been successfully adapted to a commercial serum-free medium (SFM; SF900-II) by gradually reducing the serum-containing TC-100 medium content from 100 to 0% (v/v). 24934233 2 23 theme culture 359:365 arg1 flask 367:371 the culture flask 355:371 the culture flask 355:371 The BmN4 cells adapted to the SFM (BmN-SFM) adhered strongly to the culture flask and showed altered cell morphology. 24934233 4 24 link N-linked 882:889 arg1 glycans 891:897 N-linked glycans 882:897 N-linked glycans in BmN-SFM cells 882:914 Additionally, mouse interleukin-3 expressed by a recombinant BmNPV was normally secreted and modified with N-linked glycans in BmN-SFM cells. 24934233 3 25 theme B. 564:565 arg1 BmNPV 594:598 BmNPV 594:598 BmNPV 594:598 The BmN-SFM was subcultured 200 times, and the population doubling time was 4.70 d. Infection studies showed that BmN-SFM cells were easily susceptible to B. mori nucleopolyhedrovirus (BmNPV), and both the multiplication of budded virus and the promoter activity of the polyhedrin gene in BmN-SFM cells were almost the same as those in BmN4 cells before adaptation. 24934233 3 25 theme B. 564:565 arg1 nucleopolyhedrovirus 572:591 B. mori nucleopolyhedrovirus 564:591 B. mori nucleopolyhedrovirus (BmNPV) 564:599 The BmN-SFM was subcultured 200 times, and the population doubling time was 4.70 d. Infection studies showed that BmN-SFM cells were easily susceptible to B. mori nucleopolyhedrovirus (BmNPV), and both the multiplication of budded virus and the promoter activity of the polyhedrin gene in BmN-SFM cells were almost the same as those in BmN4 cells before adaptation. 24934233 1 26 theme Bombyx 86:91 arg1 mori 93:96 Bombyx mori 86:96 Bombyx mori ovary-derived BmN4 cells 86:121 Bombyx mori ovary-derived BmN4 cells have been successfully adapted to a commercial serum-free medium (SFM; SF900-II) by gradually reducing the serum-containing TC-100 medium content from 100 to 0% (v/v). 24934233 2 27 theme altered 384:390 arg1 morphology 397:406 altered cell morphology 384:406 altered cell morphology 384:406 The BmN4 cells adapted to the SFM (BmN-SFM) adhered strongly to the culture flask and showed altered cell morphology. 24934233 0 28 theme mori 35:38 arg1 line 50:53 the Bombyx mori BmN4 cell line 24:53 the Bombyx mori BmN4 cell line 24:53 Long-term adaptation of the Bombyx mori BmN4 cell line to grow in serum-free culture. 24934233 3 29 theme mori 567:570 arg1 BmNPV 594:598 BmNPV 594:598 BmNPV 594:598 The BmN-SFM was subcultured 200 times, and the population doubling time was 4.70 d. Infection studies showed that BmN-SFM cells were easily susceptible to B. mori nucleopolyhedrovirus (BmNPV), and both the multiplication of budded virus and the promoter activity of the polyhedrin gene in BmN-SFM cells were almost the same as those in BmN4 cells before adaptation. 24934233 3 29 theme mori 567:570 arg1 nucleopolyhedrovirus 572:591 B. mori nucleopolyhedrovirus 564:591 B. mori nucleopolyhedrovirus (BmNPV) 564:599 The BmN-SFM was subcultured 200 times, and the population doubling time was 4.70 d. Infection studies showed that BmN-SFM cells were easily susceptible to B. mori nucleopolyhedrovirus (BmNPV), and both the multiplication of budded virus and the promoter activity of the polyhedrin gene in BmN-SFM cells were almost the same as those in BmN4 cells before adaptation. 24934233 4 30 theme recombinant 824:834 arg1 BmNPV 836:840 a recombinant BmNPV 822:840 a recombinant BmNPV 822:840 Additionally, mouse interleukin-3 expressed by a recombinant BmNPV was normally secreted and modified with N-linked glycans in BmN-SFM cells. 24934233 0 31 theme Bombyx 28:33 arg1 mori 35:38 Bombyx mori 28:38 the Bombyx mori BmN4 cell line 24:53 Long-term adaptation of the Bombyx mori BmN4 cell line to grow in serum-free culture. 24934233 3 32 theme polyhedrin 679:688 arg1 gene 690:693 the polyhedrin gene 675:693 the polyhedrin gene 675:693 The BmN-SFM was subcultured 200 times, and the population doubling time was 4.70 d. Infection studies showed that BmN-SFM cells were easily susceptible to B. mori nucleopolyhedrovirus (BmNPV), and both the multiplication of budded virus and the promoter activity of the polyhedrin gene in BmN-SFM cells were almost the same as those in BmN4 cells before adaptation. 24934233 2 33 theme cell 392:395 arg1 morphology 397:406 altered cell morphology 384:406 altered cell morphology 384:406 The BmN4 cells adapted to the SFM (BmN-SFM) adhered strongly to the culture flask and showed altered cell morphology. 24934233 5 34 theme BmNPV-based 983:993 arg1 system 1025:1030 a BmNPV-based baculovirus expression vector system 981:1030 a BmNPV-based baculovirus expression vector system with serum-free conditions 981:1057 These findings indicate that BmN-SFM is particularly useful for a BmNPV-based baculovirus expression vector system with serum-free conditions. 24934233 0 35 theme cell 45:48 arg1 line 50:53 the Bombyx mori BmN4 cell line 24:53 the Bombyx mori BmN4 cell line 24:53 Long-term adaptation of the Bombyx mori BmN4 cell line to grow in serum-free culture. 24934233 3 36 theme gene 690:693 arg1 activity 663:670 the promoter activity 650:670 the promoter activity of the polyhedrin gene in BmN-SFM cells 650:710 The BmN-SFM was subcultured 200 times, and the population doubling time was 4.70 d. Infection studies showed that BmN-SFM cells were easily susceptible to B. mori nucleopolyhedrovirus (BmNPV), and both the multiplication of budded virus and the promoter activity of the polyhedrin gene in BmN-SFM cells were almost the same as those in BmN4 cells before adaptation. 24934233 3 36 theme gene 690:693 arg1 same 728:731 same 728:731 same 728:731 The BmN-SFM was subcultured 200 times, and the population doubling time was 4.70 d. Infection studies showed that BmN-SFM cells were easily susceptible to B. mori nucleopolyhedrovirus (BmNPV), and both the multiplication of budded virus and the promoter activity of the polyhedrin gene in BmN-SFM cells were almost the same as those in BmN4 cells before adaptation. 24934233 3 36 theme gene 690:693 arg1 multiplication 615:628 the multiplication 611:628 the multiplication of budded virus 611:644 The BmN-SFM was subcultured 200 times, and the population doubling time was 4.70 d. Infection studies showed that BmN-SFM cells were easily susceptible to B. mori nucleopolyhedrovirus (BmNPV), and both the multiplication of budded virus and the promoter activity of the polyhedrin gene in BmN-SFM cells were almost the same as those in BmN4 cells before adaptation. 24934233 4 37 theme mouse 789:793 arg1 interleukin-3 795:807 mouse interleukin-3 789:807 mouse interleukin-3 expressed by a recombinant BmNPV 789:840 Additionally, mouse interleukin-3 expressed by a recombinant BmNPV was normally secreted and modified with N-linked glycans in BmN-SFM cells. 24934233 5 38 theme baculovirus 995:1005 arg1 system 1025:1030 a BmNPV-based baculovirus expression vector system 981:1030 a BmNPV-based baculovirus expression vector system with serum-free conditions 981:1057 These findings indicate that BmN-SFM is particularly useful for a BmNPV-based baculovirus expression vector system with serum-free conditions. 24934233 3 39 theme Infection 493:501 arg1 studies 503:509 d. Infection studies 490:509 d. Infection studies 490:509 The BmN-SFM was subcultured 200 times, and the population doubling time was 4.70 d. Infection studies showed that BmN-SFM cells were easily susceptible to B. mori nucleopolyhedrovirus (BmNPV), and both the multiplication of budded virus and the promoter activity of the polyhedrin gene in BmN-SFM cells were almost the same as those in BmN4 cells before adaptation. 24934233 1 40 theme mori 93:96 arg1 cells 117:121 Bombyx mori ovary-derived BmN4 cells 86:121 Bombyx mori ovary-derived BmN4 cells 86:121 Bombyx mori ovary-derived BmN4 cells have been successfully adapted to a commercial serum-free medium (SFM; SF900-II) by gradually reducing the serum-containing TC-100 medium content from 100 to 0% (v/v). 24934233 0 41 theme BmN4 40:43 arg1 line 50:53 the Bombyx mori BmN4 cell line 24:53 the Bombyx mori BmN4 cell line 24:53 Long-term adaptation of the Bombyx mori BmN4 cell line to grow in serum-free culture. 24934233 1 42 theme ovary-derived 98:110 arg1 cells 117:121 Bombyx mori ovary-derived BmN4 cells 86:121 Bombyx mori ovary-derived BmN4 cells 86:121 Bombyx mori ovary-derived BmN4 cells have been successfully adapted to a commercial serum-free medium (SFM; SF900-II) by gradually reducing the serum-containing TC-100 medium content from 100 to 0% (v/v). 24934233 3 43 theme BmN4 745:748 arg1 cells 750:754 BmN4 cells 745:754 BmN4 cells before adaptation 745:772 The BmN-SFM was subcultured 200 times, and the population doubling time was 4.70 d. Infection studies showed that BmN-SFM cells were easily susceptible to B. mori nucleopolyhedrovirus (BmNPV), and both the multiplication of budded virus and the promoter activity of the polyhedrin gene in BmN-SFM cells were almost the same as those in BmN4 cells before adaptation. 24934233 2 44 dep SFM 321:323 arg1 adhered 335:341 adhered 335:341 adhered 335:341 The BmN4 cells adapted to the SFM (BmN-SFM) adhered strongly to the culture flask and showed altered cell morphology. 24934233 1 45 dep SFM 189:191 arg1 SF900-II 194:201 SF900-II 194:201 SFM; SF900-II 189:201 Bombyx mori ovary-derived BmN4 cells have been successfully adapted to a commercial serum-free medium (SFM; SF900-II) by gradually reducing the serum-containing TC-100 medium content from 100 to 0% (v/v). 24934233 1 46 theme BmN4 112:115 arg1 cells 117:121 Bombyx mori ovary-derived BmN4 cells 86:121 Bombyx mori ovary-derived BmN4 cells 86:121 Bombyx mori ovary-derived BmN4 cells have been successfully adapted to a commercial serum-free medium (SFM; SF900-II) by gradually reducing the serum-containing TC-100 medium content from 100 to 0% (v/v). 24934233 4 47 from glycans 891:897 arg1 cells 910:914 BmN-SFM cells 902:914 BmN-SFM cells 902:914 Additionally, mouse interleukin-3 expressed by a recombinant BmNPV was normally secreted and modified with N-linked glycans in BmN-SFM cells. 24934233 1 48 link ovary-derived 98:110 arg1 cells 117:121 Bombyx mori ovary-derived BmN4 cells 86:121 Bombyx mori ovary-derived BmN4 cells 86:121 Bombyx mori ovary-derived BmN4 cells have been successfully adapted to a commercial serum-free medium (SFM; SF900-II) by gradually reducing the serum-containing TC-100 medium content from 100 to 0% (v/v). 24934233 5 49 with system 1025:1030 arg1 conditions 1048:1057 serum-free conditions 1037:1057 serum-free conditions 1037:1057 These findings indicate that BmN-SFM is particularly useful for a BmNPV-based baculovirus expression vector system with serum-free conditions. 24934233 3 50 theme BmN-SFM 523:529 arg1 cells 531:535 BmN-SFM cells 523:535 BmN-SFM cells 523:535 The BmN-SFM was subcultured 200 times, and the population doubling time was 4.70 d. Infection studies showed that BmN-SFM cells were easily susceptible to B. mori nucleopolyhedrovirus (BmNPV), and both the multiplication of budded virus and the promoter activity of the polyhedrin gene in BmN-SFM cells were almost the same as those in BmN4 cells before adaptation. 24934233 0 51 theme line 50:53 arg1 adaptation 10:19 Long-term adaptation 0:19 Long-term adaptation of the Bombyx mori BmN4 cell line 0:53 Long-term adaptation of the Bombyx mori BmN4 cell line to grow in serum-free culture. 24934233 5 52 theme serum-free 1037:1046 arg1 conditions 1048:1057 serum-free conditions 1037:1057 serum-free conditions 1037:1057 These findings indicate that BmN-SFM is particularly useful for a BmNPV-based baculovirus expression vector system with serum-free conditions. 24934233 3 53 theme BmN-SFM 698:704 arg1 cells 706:710 BmN-SFM cells 698:710 BmN-SFM cells 698:710 The BmN-SFM was subcultured 200 times, and the population doubling time was 4.70 d. Infection studies showed that BmN-SFM cells were easily susceptible to B. mori nucleopolyhedrovirus (BmNPV), and both the multiplication of budded virus and the promoter activity of the polyhedrin gene in BmN-SFM cells were almost the same as those in BmN4 cells before adaptation. 28928222 6 0 gly N-glycosylation 1642:1656 arg2 sites 1658:1662 all the putative N-glycosylation sites 1625:1662 all the putative N-glycosylation sites in the parasite proteome 1625:1687 Using machine learning, we assessed the features that best define TbSTT3A and TbSTT3B substrates in vivo and built an algorithm to predict the types of N-glycan most likely to predominate at all the putative N-glycosylation sites in the parasite proteome. 28928222 5 1 theme H-sensitive 1347:1357 arg1 N-glycans 1359:1367 endoglycosidase H-sensitive N-glycans 1331:1367 endoglycosidase H-sensitive N-glycans originating from Man9GlcNAc2-PP-dolichol transferred by TbSTT3B 1331:1431 This allowed us to assess the relative occupancies of numerous N-glycosylation sites by endoglycosidase H-resistant N-glycans originating from Man5GlcNAc2-PP-dolichol transferred by TbSTT3A, and endoglycosidase H-sensitive N-glycans originating from Man9GlcNAc2-PP-dolichol transferred by TbSTT3B. 28928222 2 2 dep architecture 587:598 arg1 the 577:579 the 577:579 the 577:579 These OSTs have different peptide acceptor and lipid-linked oligosaccharide donor specificities, and trypanosomes do not follow many of the canonical rules developed for other eukaryotic N-glycosylation pathways, raising questions as to the basic architecture and detailed function of trypanosome OSTs. 28928222 4 3 theme in 938:939 arg1 OSTs 933:936 the OSTs 929:936 the OSTs in vivo 929:944 We probed the peptide acceptor specificities of the OSTs in vivo using a transgenic glycoprotein reporter system and performed glycoproteomics on endogenous parasite glycoproteins using sequential endoglycosidase H and peptide:N-glycosidase-F digestions. 28928222 2 4 link lipid-linked 387:398 arg1 specificities 422:434 different peptide acceptor and lipid-linked oligosaccharide donor specificities 356:434 specificities 422:434 These OSTs have different peptide acceptor and lipid-linked oligosaccharide donor specificities, and trypanosomes do not follow many of the canonical rules developed for other eukaryotic N-glycosylation pathways, raising questions as to the basic architecture and detailed function of trypanosome OSTs. 28928222 1 5 theme African 156:162 arg1 trypanosomiasis 164:178 African trypanosomiasis 156:178 African trypanosomiasis 156:178 Trypanosoma brucei causes African trypanosomiasis and contains three full-length oligosaccharyltransferase (OST) genes; two of which, TbSTT3A and TbSTT3B, are expressed in the bloodstream form of the parasite. 28928222 4 6 theme peptide 895:901 arg1 specificities 912:924 the peptide acceptor specificities 891:924 the peptide acceptor specificities of the OSTs in vivo 891:944 We probed the peptide acceptor specificities of the OSTs in vivo using a transgenic glycoprotein reporter system and performed glycoproteomics on endogenous parasite glycoproteins using sequential endoglycosidase H and peptide:N-glycosidase-F digestions. 28928222 9 7 with ProteomeXchange 2045:2059 arg1 identifiers 2066:2076 identifiers PXD007236, PXD007267, and PXD007268 2066:2112 identifiers PXD007236, PXD007267, and PXD007268 2066:2112 Data are available via ProteomeXchange with identifiers PXD007236, PXD007267, and PXD007268. 28928222 2 8 theme detailed 604:611 arg1 function 613:620 detailed function 604:620 detailed function 604:620 These OSTs have different peptide acceptor and lipid-linked oligosaccharide donor specificities, and trypanosomes do not follow many of the canonical rules developed for other eukaryotic N-glycosylation pathways, raising questions as to the basic architecture and detailed function of trypanosome OSTs. 28928222 6 9 theme parasite 1671:1678 arg1 proteome 1680:1687 the parasite proteome 1667:1687 the parasite proteome 1667:1687 Using machine learning, we assessed the features that best define TbSTT3A and TbSTT3B substrates in vivo and built an algorithm to predict the types of N-glycan most likely to predominate at all the putative N-glycosylation sites in the parasite proteome. 28928222 5 10 gly N-glycosylation 1199:1213 arg2 sites 1215:1219 numerous N-glycosylation sites 1190:1219 numerous N-glycosylation sites 1190:1219 This allowed us to assess the relative occupancies of numerous N-glycosylation sites by endoglycosidase H-resistant N-glycans originating from Man5GlcNAc2-PP-dolichol transferred by TbSTT3A, and endoglycosidase H-sensitive N-glycans originating from Man9GlcNAc2-PP-dolichol transferred by TbSTT3B. 28928222 5 11 theme relative 1166:1173 arg1 occupancies 1175:1185 the relative occupancies 1162:1185 the relative occupancies of numerous N-glycosylation sites 1162:1219 This allowed us to assess the relative occupancies of numerous N-glycosylation sites by endoglycosidase H-resistant N-glycans originating from Man5GlcNAc2-PP-dolichol transferred by TbSTT3A, and endoglycosidase H-sensitive N-glycans originating from Man9GlcNAc2-PP-dolichol transferred by TbSTT3B. 28928222 2 12 theme OSTs 637:640 arg1 architecture 587:598 basic architecture 581:598 basic architecture 581:598 These OSTs have different peptide acceptor and lipid-linked oligosaccharide donor specificities, and trypanosomes do not follow many of the canonical rules developed for other eukaryotic N-glycosylation pathways, raising questions as to the basic architecture and detailed function of trypanosome OSTs. 28928222 2 12 theme OSTs 637:640 arg1 function 613:620 detailed function 604:620 detailed function 604:620 These OSTs have different peptide acceptor and lipid-linked oligosaccharide donor specificities, and trypanosomes do not follow many of the canonical rules developed for other eukaryotic N-glycosylation pathways, raising questions as to the basic architecture and detailed function of trypanosome OSTs. 28928222 3 13 theme large 814:818 arg1 complexes 820:828 large complexes 814:828 large complexes that contain no other detectable protein subunits 814:878 Here, we show by blue-native gel electrophoresis and stable isotope labeling in cell culture proteomics that the TbSTT3A and TbSTT3B proteins associate with each other in large complexes that contain no other detectable protein subunits. 28928222 8 14 theme protein 1937:1943 arg1 N-glycosylation 1945:1959 re-wired protein N-glycosylation 1928:1959 re-wired protein N-glycosylation 1928:1959 Together, these studies provide insights into how a highly divergent eukaryote has re-wired protein N-glycosylation to provide protein sequence-specific N-glycan modifications. 28928222 4 15 theme transgenic 954:963 arg1 system 987:992 a transgenic glycoprotein reporter system 952:992 a transgenic glycoprotein reporter system 952:992 We probed the peptide acceptor specificities of the OSTs in vivo using a transgenic glycoprotein reporter system and performed glycoproteomics on endogenous parasite glycoproteins using sequential endoglycosidase H and peptide:N-glycosidase-F digestions. 28928222 3 16 theme detectable 852:861 arg1 subunits 871:878 no other detectable protein subunits 843:878 no other detectable protein subunits 843:878 Here, we show by blue-native gel electrophoresis and stable isotope labeling in cell culture proteomics that the TbSTT3A and TbSTT3B proteins associate with each other in large complexes that contain no other detectable protein subunits. 28928222 3 17 theme gel 672:674 arg1 electrophoresis 676:690 blue-native gel electrophoresis 660:690 blue-native gel electrophoresis 660:690 Here, we show by blue-native gel electrophoresis and stable isotope labeling in cell culture proteomics that the TbSTT3A and TbSTT3B proteins associate with each other in large complexes that contain no other detectable protein subunits. 28928222 4 18 theme reporter 978:985 arg1 system 987:992 a transgenic glycoprotein reporter system 952:992 a transgenic glycoprotein reporter system 952:992 We probed the peptide acceptor specificities of the OSTs in vivo using a transgenic glycoprotein reporter system and performed glycoproteomics on endogenous parasite glycoproteins using sequential endoglycosidase H and peptide:N-glycosidase-F digestions. 28928222 0 19 theme predictable 86:96 arg1 specificities 115:127 different and predictable peptide acceptor specificities 72:127 different and predictable peptide acceptor specificities 72:127 Single-subunit oligosaccharyltransferases of Trypanosoma brucei display different and predictable peptide acceptor specificities. 28928222 2 20 contain have 351:354 arg2 specificities 422:434 different peptide acceptor and lipid-linked oligosaccharide donor specificities 356:434 specificities 422:434 These OSTs have different peptide acceptor and lipid-linked oligosaccharide donor specificities, and trypanosomes do not follow many of the canonical rules developed for other eukaryotic N-glycosylation pathways, raising questions as to the basic architecture and detailed function of trypanosome OSTs. 28928222 2 20 contain have 351:354 arg2 acceptor 374:381 different peptide acceptor and lipid-linked oligosaccharide donor specificities 356:434 acceptor 374:381 These OSTs have different peptide acceptor and lipid-linked oligosaccharide donor specificities, and trypanosomes do not follow many of the canonical rules developed for other eukaryotic N-glycosylation pathways, raising questions as to the basic architecture and detailed function of trypanosome OSTs. 28928222 2 20 contain have 351:354 arg1 OSTs 346:349 These OSTs 340:349 These OSTs 340:349 These OSTs have different peptide acceptor and lipid-linked oligosaccharide donor specificities, and trypanosomes do not follow many of the canonical rules developed for other eukaryotic N-glycosylation pathways, raising questions as to the basic architecture and detailed function of trypanosome OSTs. 28928222 8 21 theme protein 1972:1978 arg1 modifications 2007:2019 protein sequence-specific N-glycan modifications 1972:2019 protein sequence-specific N-glycan modifications 1972:2019 Together, these studies provide insights into how a highly divergent eukaryote has re-wired protein N-glycosylation to provide protein sequence-specific N-glycan modifications. 28928222 1 22 theme full-length 199:209 arg1 genes 243:247 three full-length oligosaccharyltransferase (OST) genes 193:247 three full-length oligosaccharyltransferase (OST) genes 193:247 Trypanosoma brucei causes African trypanosomiasis and contains three full-length oligosaccharyltransferase (OST) genes; two of which, TbSTT3A and TbSTT3B, are expressed in the bloodstream form of the parasite. 28928222 4 23 theme sequential 1067:1076 arg1 H 1094:1094 sequential endoglycosidase H and peptide:N-glycosidase-F digestions 1067:1133 H 1094:1094 We probed the peptide acceptor specificities of the OSTs in vivo using a transgenic glycoprotein reporter system and performed glycoproteomics on endogenous parasite glycoproteins using sequential endoglycosidase H and peptide:N-glycosidase-F digestions. 28928222 0 24 theme acceptor 106:113 arg1 specificities 115:127 different and predictable peptide acceptor specificities 72:127 different and predictable peptide acceptor specificities 72:127 Single-subunit oligosaccharyltransferases of Trypanosoma brucei display different and predictable peptide acceptor specificities. 28928222 5 25 theme H-resistant 1240:1250 arg1 N-glycans 1252:1260 endoglycosidase H-resistant N-glycans 1224:1260 endoglycosidase H-resistant N-glycans originating from Man5GlcNAc2-PP-dolichol transferred by TbSTT3A 1224:1324 This allowed us to assess the relative occupancies of numerous N-glycosylation sites by endoglycosidase H-resistant N-glycans originating from Man5GlcNAc2-PP-dolichol transferred by TbSTT3A, and endoglycosidase H-sensitive N-glycans originating from Man9GlcNAc2-PP-dolichol transferred by TbSTT3B. 28928222 8 26 theme N-glycan 1998:2005 arg1 modifications 2007:2019 protein sequence-specific N-glycan modifications 1972:2019 protein sequence-specific N-glycan modifications 1972:2019 Together, these studies provide insights into how a highly divergent eukaryote has re-wired protein N-glycosylation to provide protein sequence-specific N-glycan modifications. 28928222 4 27 gly glycoproteins 1047:1059 arg1 glycoproteins 1047:1059 endogenous parasite glycoproteins 1027:1059 endogenous parasite glycoproteins 1027:1059 We probed the peptide acceptor specificities of the OSTs in vivo using a transgenic glycoprotein reporter system and performed glycoproteomics on endogenous parasite glycoproteins using sequential endoglycosidase H and peptide:N-glycosidase-F digestions. 28928222 4 28 theme endogenous 1027:1036 arg1 glycoproteins 1047:1059 endogenous parasite glycoproteins 1027:1059 endogenous parasite glycoproteins 1027:1059 We probed the peptide acceptor specificities of the OSTs in vivo using a transgenic glycoprotein reporter system and performed glycoproteomics on endogenous parasite glycoproteins using sequential endoglycosidase H and peptide:N-glycosidase-F digestions. 28928222 3 29 contain contain 835:841 arg1 complexes 820:828 large complexes 814:828 large complexes that contain no other detectable protein subunits 814:878 Here, we show by blue-native gel electrophoresis and stable isotope labeling in cell culture proteomics that the TbSTT3A and TbSTT3B proteins associate with each other in large complexes that contain no other detectable protein subunits. 28928222 3 29 contain contain 835:841 arg2 subunits 871:878 no other detectable protein subunits 843:878 no other detectable protein subunits 843:878 Here, we show by blue-native gel electrophoresis and stable isotope labeling in cell culture proteomics that the TbSTT3A and TbSTT3B proteins associate with each other in large complexes that contain no other detectable protein subunits. 28928222 5 30 theme N-glycosylation 1199:1213 arg1 sites 1215:1219 numerous N-glycosylation sites 1190:1219 numerous N-glycosylation sites 1190:1219 This allowed us to assess the relative occupancies of numerous N-glycosylation sites by endoglycosidase H-resistant N-glycans originating from Man5GlcNAc2-PP-dolichol transferred by TbSTT3A, and endoglycosidase H-sensitive N-glycans originating from Man9GlcNAc2-PP-dolichol transferred by TbSTT3B. 28928222 4 31 theme N-glycosidase-F 1108:1122 arg1 digestions 1124:1133 sequential endoglycosidase H and peptide:N-glycosidase-F digestions 1067:1133 digestions 1124:1133 We probed the peptide acceptor specificities of the OSTs in vivo using a transgenic glycoprotein reporter system and performed glycoproteomics on endogenous parasite glycoproteins using sequential endoglycosidase H and peptide:N-glycosidase-F digestions. 28928222 0 32 theme Single-subunit 0:13 arg1 oligosaccharyltransferases 15:40 Single-subunit oligosaccharyltransferases 0:40 Single-subunit oligosaccharyltransferases of Trypanosoma brucei 0:62 Single-subunit oligosaccharyltransferases of Trypanosoma brucei display different and predictable peptide acceptor specificities. 28928222 1 33 theme bloodstream 306:316 arg1 form 318:321 the bloodstream form 302:321 the bloodstream form of the parasite 302:337 Trypanosoma brucei causes African trypanosomiasis and contains three full-length oligosaccharyltransferase (OST) genes; two of which, TbSTT3A and TbSTT3B, are expressed in the bloodstream form of the parasite. 28928222 1 34 theme Trypanosoma 130:140 arg1 brucei 142:147 Trypanosoma brucei 130:147 Trypanosoma brucei 130:147 Trypanosoma brucei causes African trypanosomiasis and contains three full-length oligosaccharyltransferase (OST) genes; two of which, TbSTT3A and TbSTT3B, are expressed in the bloodstream form of the parasite. 28928222 7 35 theme acid 1830:1833 arg1 residues 1835:1842 acidic amino acid residues 1817:1842 acidic amino acid residues 1817:1842 Finally, molecular modeling was used to suggest why TbSTT3A has a distinct preference for sequons containing and/or flanked by acidic amino acid residues. 28928222 6 36 theme N-glycan 1586:1593 arg1 types 1577:1581 the types 1573:1581 the types of N-glycan 1573:1593 Using machine learning, we assessed the features that best define TbSTT3A and TbSTT3B substrates in vivo and built an algorithm to predict the types of N-glycan most likely to predominate at all the putative N-glycosylation sites in the parasite proteome. 28928222 7 37 theme molecular 1699:1707 arg1 modeling 1709:1716 molecular modeling 1699:1716 molecular modeling 1699:1716 Finally, molecular modeling was used to suggest why TbSTT3A has a distinct preference for sequons containing and/or flanked by acidic amino acid residues. 28928222 7 38 theme acidic 1817:1822 arg1 residues 1835:1842 acidic amino acid residues 1817:1842 acidic amino acid residues 1817:1842 Finally, molecular modeling was used to suggest why TbSTT3A has a distinct preference for sequons containing and/or flanked by acidic amino acid residues. 28928222 2 39 theme eukaryotic 516:525 arg1 pathways 543:550 other eukaryotic N-glycosylation pathways 510:550 other eukaryotic N-glycosylation pathways 510:550 These OSTs have different peptide acceptor and lipid-linked oligosaccharide donor specificities, and trypanosomes do not follow many of the canonical rules developed for other eukaryotic N-glycosylation pathways, raising questions as to the basic architecture and detailed function of trypanosome OSTs. 28928222 3 40 theme isotope 703:709 arg1 labeling 711:718 stable isotope labeling 696:718 stable isotope labeling 696:718 Here, we show by blue-native gel electrophoresis and stable isotope labeling in cell culture proteomics that the TbSTT3A and TbSTT3B proteins associate with each other in large complexes that contain no other detectable protein subunits. 28928222 0 41 theme brucei 57:62 arg1 oligosaccharyltransferases 15:40 Single-subunit oligosaccharyltransferases 0:40 Single-subunit oligosaccharyltransferases of Trypanosoma brucei 0:62 Single-subunit oligosaccharyltransferases of Trypanosoma brucei display different and predictable peptide acceptor specificities. 28928222 1 42 theme parasite 330:337 arg1 form 318:321 the bloodstream form 302:321 the bloodstream form of the parasite 302:337 Trypanosoma brucei causes African trypanosomiasis and contains three full-length oligosaccharyltransferase (OST) genes; two of which, TbSTT3A and TbSTT3B, are expressed in the bloodstream form of the parasite. 28928222 2 43 theme other 510:514 arg1 pathways 543:550 other eukaryotic N-glycosylation pathways 510:550 other eukaryotic N-glycosylation pathways 510:550 These OSTs have different peptide acceptor and lipid-linked oligosaccharide donor specificities, and trypanosomes do not follow many of the canonical rules developed for other eukaryotic N-glycosylation pathways, raising questions as to the basic architecture and detailed function of trypanosome OSTs. 28928222 4 44 theme peptide 1100:1106 arg1 digestions 1124:1133 sequential endoglycosidase H and peptide:N-glycosidase-F digestions 1067:1133 digestions 1124:1133 We probed the peptide acceptor specificities of the OSTs in vivo using a transgenic glycoprotein reporter system and performed glycoproteomics on endogenous parasite glycoproteins using sequential endoglycosidase H and peptide:N-glycosidase-F digestions. 28928222 0 45 theme different 72:80 arg1 specificities 115:127 different and predictable peptide acceptor specificities 72:127 different and predictable peptide acceptor specificities 72:127 Single-subunit oligosaccharyltransferases of Trypanosoma brucei display different and predictable peptide acceptor specificities. 28928222 6 46 from sites 1658:1662 arg1 proteome 1680:1687 the parasite proteome 1667:1687 the parasite proteome 1667:1687 Using machine learning, we assessed the features that best define TbSTT3A and TbSTT3B substrates in vivo and built an algorithm to predict the types of N-glycan most likely to predominate at all the putative N-glycosylation sites in the parasite proteome. 28928222 3 47 theme culture 728:734 arg1 proteomics 736:745 cell culture proteomics 723:745 cell culture proteomics 723:745 Here, we show by blue-native gel electrophoresis and stable isotope labeling in cell culture proteomics that the TbSTT3A and TbSTT3B proteins associate with each other in large complexes that contain no other detectable protein subunits. 28928222 2 48 theme different 356:364 arg1 acceptor 374:381 different peptide acceptor and lipid-linked oligosaccharide donor specificities 356:434 acceptor 374:381 These OSTs have different peptide acceptor and lipid-linked oligosaccharide donor specificities, and trypanosomes do not follow many of the canonical rules developed for other eukaryotic N-glycosylation pathways, raising questions as to the basic architecture and detailed function of trypanosome OSTs. 28928222 5 49 gly occupancies 1175:1185 arg2 sites 1215:1219 numerous N-glycosylation sites 1190:1219 numerous N-glycosylation sites 1190:1219 This allowed us to assess the relative occupancies of numerous N-glycosylation sites by endoglycosidase H-resistant N-glycans originating from Man5GlcNAc2-PP-dolichol transferred by TbSTT3A, and endoglycosidase H-sensitive N-glycans originating from Man9GlcNAc2-PP-dolichol transferred by TbSTT3B. 28928222 3 50 from labeling 711:718 arg1 proteomics 736:745 cell culture proteomics 723:745 cell culture proteomics 723:745 Here, we show by blue-native gel electrophoresis and stable isotope labeling in cell culture proteomics that the TbSTT3A and TbSTT3B proteins associate with each other in large complexes that contain no other detectable protein subunits. 28928222 2 51 theme donor 416:420 arg1 specificities 422:434 different peptide acceptor and lipid-linked oligosaccharide donor specificities 356:434 specificities 422:434 These OSTs have different peptide acceptor and lipid-linked oligosaccharide donor specificities, and trypanosomes do not follow many of the canonical rules developed for other eukaryotic N-glycosylation pathways, raising questions as to the basic architecture and detailed function of trypanosome OSTs. 28928222 6 52 theme putative 1633:1640 arg1 sites 1658:1662 all the putative N-glycosylation sites 1625:1662 all the putative N-glycosylation sites in the parasite proteome 1625:1687 Using machine learning, we assessed the features that best define TbSTT3A and TbSTT3B substrates in vivo and built an algorithm to predict the types of N-glycan most likely to predominate at all the putative N-glycosylation sites in the parasite proteome. 28928222 7 53 contain has 1750:1752 arg1 TbSTT3A 1742:1748 TbSTT3A 1742:1748 TbSTT3A 1742:1748 Finally, molecular modeling was used to suggest why TbSTT3A has a distinct preference for sequons containing and/or flanked by acidic amino acid residues. 28928222 7 53 contain has 1750:1752 arg2 preference 1765:1774 a distinct preference 1754:1774 a distinct preference for sequons containing and/or flanked by acidic amino acid residues 1754:1842 Finally, molecular modeling was used to suggest why TbSTT3A has a distinct preference for sequons containing and/or flanked by acidic amino acid residues. 28928222 3 54 theme TbSTT3A 756:762 arg1 proteins 776:783 the TbSTT3A and TbSTT3B proteins 752:783 the TbSTT3A and TbSTT3B proteins 752:783 Here, we show by blue-native gel electrophoresis and stable isotope labeling in cell culture proteomics that the TbSTT3A and TbSTT3B proteins associate with each other in large complexes that contain no other detectable protein subunits. 28928222 2 55 theme lipid-linked 387:398 arg1 specificities 422:434 different peptide acceptor and lipid-linked oligosaccharide donor specificities 356:434 specificities 422:434 These OSTs have different peptide acceptor and lipid-linked oligosaccharide donor specificities, and trypanosomes do not follow many of the canonical rules developed for other eukaryotic N-glycosylation pathways, raising questions as to the basic architecture and detailed function of trypanosome OSTs. 28928222 3 56 from electrophoresis 676:690 arg1 proteomics 736:745 cell culture proteomics 723:745 cell culture proteomics 723:745 Here, we show by blue-native gel electrophoresis and stable isotope labeling in cell culture proteomics that the TbSTT3A and TbSTT3B proteins associate with each other in large complexes that contain no other detectable protein subunits. 28928222 4 57 from glycoproteomics 1008:1022 arg1 glycoproteins 1047:1059 endogenous parasite glycoproteins 1027:1059 endogenous parasite glycoproteins 1027:1059 We probed the peptide acceptor specificities of the OSTs in vivo using a transgenic glycoprotein reporter system and performed glycoproteomics on endogenous parasite glycoproteins using sequential endoglycosidase H and peptide:N-glycosidase-F digestions. 28928222 4 58 theme OSTs 933:936 arg1 specificities 912:924 the peptide acceptor specificities 891:924 the peptide acceptor specificities of the OSTs in vivo 891:944 We probed the peptide acceptor specificities of the OSTs in vivo using a transgenic glycoprotein reporter system and performed glycoproteomics on endogenous parasite glycoproteins using sequential endoglycosidase H and peptide:N-glycosidase-F digestions. 28928222 6 59 theme machine 1440:1446 arg1 learning 1448:1455 machine learning 1440:1455 machine learning 1440:1455 Using machine learning, we assessed the features that best define TbSTT3A and TbSTT3B substrates in vivo and built an algorithm to predict the types of N-glycan most likely to predominate at all the putative N-glycosylation sites in the parasite proteome. 28928222 3 60 theme TbSTT3B 768:774 arg1 proteins 776:783 the TbSTT3A and TbSTT3B proteins 752:783 the TbSTT3A and TbSTT3B proteins 752:783 Here, we show by blue-native gel electrophoresis and stable isotope labeling in cell culture proteomics that the TbSTT3A and TbSTT3B proteins associate with each other in large complexes that contain no other detectable protein subunits. 28928222 7 61 dep sequons 1780:1786 arg1 flanked 1806:1812 flanked 1806:1812 flanked by acidic amino acid residues 1806:1842 Finally, molecular modeling was used to suggest why TbSTT3A has a distinct preference for sequons containing and/or flanked by acidic amino acid residues. 28928222 7 61 dep sequons 1780:1786 arg1 containing 1788:1797 containing 1788:1797 containing 1788:1797 Finally, molecular modeling was used to suggest why TbSTT3A has a distinct preference for sequons containing and/or flanked by acidic amino acid residues. 28928222 4 62 theme acceptor 903:910 arg1 specificities 912:924 the peptide acceptor specificities 891:924 the peptide acceptor specificities of the OSTs in vivo 891:944 We probed the peptide acceptor specificities of the OSTs in vivo using a transgenic glycoprotein reporter system and performed glycoproteomics on endogenous parasite glycoproteins using sequential endoglycosidase H and peptide:N-glycosidase-F digestions. 28928222 6 63 theme TbSTT3B 1512:1518 arg1 substrates 1520:1529 TbSTT3A and TbSTT3B substrates 1500:1529 TbSTT3A and TbSTT3B substrates 1500:1529 Using machine learning, we assessed the features that best define TbSTT3A and TbSTT3B substrates in vivo and built an algorithm to predict the types of N-glycan most likely to predominate at all the putative N-glycosylation sites in the parasite proteome. 28928222 4 64 theme glycoprotein 965:976 arg1 system 987:992 a transgenic glycoprotein reporter system 952:992 a transgenic glycoprotein reporter system 952:992 We probed the peptide acceptor specificities of the OSTs in vivo using a transgenic glycoprotein reporter system and performed glycoproteomics on endogenous parasite glycoproteins using sequential endoglycosidase H and peptide:N-glycosidase-F digestions. 28928222 6 65 theme TbSTT3A 1500:1506 arg1 substrates 1520:1529 TbSTT3A and TbSTT3B substrates 1500:1529 TbSTT3A and TbSTT3B substrates 1500:1529 Using machine learning, we assessed the features that best define TbSTT3A and TbSTT3B substrates in vivo and built an algorithm to predict the types of N-glycan most likely to predominate at all the putative N-glycosylation sites in the parasite proteome. 28928222 1 66 theme which 257:261 arg1 TbSTT3B 276:282 TbSTT3B 276:282 TbSTT3B 276:282 Trypanosoma brucei causes African trypanosomiasis and contains three full-length oligosaccharyltransferase (OST) genes; two of which, TbSTT3A and TbSTT3B, are expressed in the bloodstream form of the parasite. 28928222 1 66 theme which 257:261 arg1 TbSTT3A 264:270 TbSTT3A 264:270 TbSTT3A 264:270 Trypanosoma brucei causes African trypanosomiasis and contains three full-length oligosaccharyltransferase (OST) genes; two of which, TbSTT3A and TbSTT3B, are expressed in the bloodstream form of the parasite. 28928222 1 66 theme which 257:261 arg1 which 257:261 which 257:261 which 257:261 Trypanosoma brucei causes African trypanosomiasis and contains three full-length oligosaccharyltransferase (OST) genes; two of which, TbSTT3A and TbSTT3B, are expressed in the bloodstream form of the parasite. 28928222 1 66 theme which 257:261 arg1 two 250:252 two 250:252 two 250:252 Trypanosoma brucei causes African trypanosomiasis and contains three full-length oligosaccharyltransferase (OST) genes; two of which, TbSTT3A and TbSTT3B, are expressed in the bloodstream form of the parasite. 28928222 2 67 theme basic 581:585 arg1 architecture 587:598 basic architecture 581:598 basic architecture 581:598 These OSTs have different peptide acceptor and lipid-linked oligosaccharide donor specificities, and trypanosomes do not follow many of the canonical rules developed for other eukaryotic N-glycosylation pathways, raising questions as to the basic architecture and detailed function of trypanosome OSTs. 28928222 4 68 gly glycoprotein 965:976 arg1 glycoprotein 965:976 a transgenic glycoprotein reporter system 952:992 a transgenic glycoprotein reporter system 952:992 We probed the peptide acceptor specificities of the OSTs in vivo using a transgenic glycoprotein reporter system and performed glycoproteomics on endogenous parasite glycoproteins using sequential endoglycosidase H and peptide:N-glycosidase-F digestions. 28928222 7 69 theme distinct 1756:1763 arg1 preference 1765:1774 a distinct preference 1754:1774 a distinct preference for sequons containing and/or flanked by acidic amino acid residues 1754:1842 Finally, molecular modeling was used to suggest why TbSTT3A has a distinct preference for sequons containing and/or flanked by acidic amino acid residues. 28928222 2 70 theme trypanosome 625:635 arg1 OSTs 637:640 trypanosome OSTs 625:640 trypanosome OSTs 625:640 These OSTs have different peptide acceptor and lipid-linked oligosaccharide donor specificities, and trypanosomes do not follow many of the canonical rules developed for other eukaryotic N-glycosylation pathways, raising questions as to the basic architecture and detailed function of trypanosome OSTs. 28928222 3 71 theme blue-native 660:670 arg1 electrophoresis 676:690 blue-native gel electrophoresis 660:690 blue-native gel electrophoresis 660:690 Here, we show by blue-native gel electrophoresis and stable isotope labeling in cell culture proteomics that the TbSTT3A and TbSTT3B proteins associate with each other in large complexes that contain no other detectable protein subunits. 28928222 8 72 theme re-wired 1928:1935 arg1 N-glycosylation 1945:1959 re-wired protein N-glycosylation 1928:1959 re-wired protein N-glycosylation 1928:1959 Together, these studies provide insights into how a highly divergent eukaryote has re-wired protein N-glycosylation to provide protein sequence-specific N-glycan modifications. 28928222 3 73 theme protein 863:869 arg1 subunits 871:878 no other detectable protein subunits 843:878 no other detectable protein subunits 843:878 Here, we show by blue-native gel electrophoresis and stable isotope labeling in cell culture proteomics that the TbSTT3A and TbSTT3B proteins associate with each other in large complexes that contain no other detectable protein subunits. 28928222 0 74 theme peptide 98:104 arg1 specificities 115:127 different and predictable peptide acceptor specificities 72:127 different and predictable peptide acceptor specificities 72:127 Single-subunit oligosaccharyltransferases of Trypanosoma brucei display different and predictable peptide acceptor specificities. 28928222 4 75 theme parasite 1038:1045 arg1 glycoproteins 1047:1059 endogenous parasite glycoproteins 1027:1059 endogenous parasite glycoproteins 1027:1059 We probed the peptide acceptor specificities of the OSTs in vivo using a transgenic glycoprotein reporter system and performed glycoproteomics on endogenous parasite glycoproteins using sequential endoglycosidase H and peptide:N-glycosidase-F digestions. 28928222 3 76 theme other 846:850 arg1 subunits 871:878 no other detectable protein subunits 843:878 no other detectable protein subunits 843:878 Here, we show by blue-native gel electrophoresis and stable isotope labeling in cell culture proteomics that the TbSTT3A and TbSTT3B proteins associate with each other in large complexes that contain no other detectable protein subunits. 28928222 1 77 theme oligosaccharyltransferase 211:235 arg1 genes 243:247 three full-length oligosaccharyltransferase (OST) genes 193:247 three full-length oligosaccharyltransferase (OST) genes 193:247 Trypanosoma brucei causes African trypanosomiasis and contains three full-length oligosaccharyltransferase (OST) genes; two of which, TbSTT3A and TbSTT3B, are expressed in the bloodstream form of the parasite. 28928222 2 78 theme N-glycosylation 527:541 arg1 pathways 543:550 other eukaryotic N-glycosylation pathways 510:550 other eukaryotic N-glycosylation pathways 510:550 These OSTs have different peptide acceptor and lipid-linked oligosaccharide donor specificities, and trypanosomes do not follow many of the canonical rules developed for other eukaryotic N-glycosylation pathways, raising questions as to the basic architecture and detailed function of trypanosome OSTs. 28928222 8 79 theme sequence-specific 1980:1996 arg1 modifications 2007:2019 protein sequence-specific N-glycan modifications 1972:2019 protein sequence-specific N-glycan modifications 1972:2019 Together, these studies provide insights into how a highly divergent eukaryote has re-wired protein N-glycosylation to provide protein sequence-specific N-glycan modifications. 28928222 7 80 used used 1722:1725 arg2 modeling 1709:1716 molecular modeling 1699:1716 molecular modeling 1699:1716 Finally, molecular modeling was used to suggest why TbSTT3A has a distinct preference for sequons containing and/or flanked by acidic amino acid residues. 28928222 8 81 theme divergent 1904:1912 arg1 eukaryote 1914:1922 a highly divergent eukaryote 1895:1922 a highly divergent eukaryote 1895:1922 Together, these studies provide insights into how a highly divergent eukaryote has re-wired protein N-glycosylation to provide protein sequence-specific N-glycan modifications. 28928222 5 82 theme numerous 1190:1197 arg1 sites 1215:1219 numerous N-glycosylation sites 1190:1219 numerous N-glycosylation sites 1190:1219 This allowed us to assess the relative occupancies of numerous N-glycosylation sites by endoglycosidase H-resistant N-glycans originating from Man5GlcNAc2-PP-dolichol transferred by TbSTT3A, and endoglycosidase H-sensitive N-glycans originating from Man9GlcNAc2-PP-dolichol transferred by TbSTT3B. 28928222 5 83 theme sites 1215:1219 arg1 occupancies 1175:1185 the relative occupancies 1162:1185 the relative occupancies of numerous N-glycosylation sites 1162:1219 This allowed us to assess the relative occupancies of numerous N-glycosylation sites by endoglycosidase H-resistant N-glycans originating from Man5GlcNAc2-PP-dolichol transferred by TbSTT3A, and endoglycosidase H-sensitive N-glycans originating from Man9GlcNAc2-PP-dolichol transferred by TbSTT3B. 28928222 2 84 theme canonical 480:488 arg1 rules 490:494 the canonical rules 476:494 the canonical rules developed for other eukaryotic N-glycosylation pathways 476:550 These OSTs have different peptide acceptor and lipid-linked oligosaccharide donor specificities, and trypanosomes do not follow many of the canonical rules developed for other eukaryotic N-glycosylation pathways, raising questions as to the basic architecture and detailed function of trypanosome OSTs. 28928222 0 85 theme Trypanosoma 45:55 arg1 brucei 57:62 Trypanosoma brucei 45:62 Trypanosoma brucei 45:62 Single-subunit oligosaccharyltransferases of Trypanosoma brucei display different and predictable peptide acceptor specificities. 28928222 3 86 theme stable 696:701 arg1 labeling 711:718 stable isotope labeling 696:718 stable isotope labeling 696:718 Here, we show by blue-native gel electrophoresis and stable isotope labeling in cell culture proteomics that the TbSTT3A and TbSTT3B proteins associate with each other in large complexes that contain no other detectable protein subunits. 28928222 4 87 dep in 938:939 arg1 vivo 941:944 vivo 941:944 vivo 941:944 We probed the peptide acceptor specificities of the OSTs in vivo using a transgenic glycoprotein reporter system and performed glycoproteomics on endogenous parasite glycoproteins using sequential endoglycosidase H and peptide:N-glycosidase-F digestions. 28928222 7 88 theme amino 1824:1828 arg1 residues 1835:1842 acidic amino acid residues 1817:1842 acidic amino acid residues 1817:1842 Finally, molecular modeling was used to suggest why TbSTT3A has a distinct preference for sequons containing and/or flanked by acidic amino acid residues. 28928222 4 89 theme endoglycosidase 1078:1092 arg1 H 1094:1094 sequential endoglycosidase H and peptide:N-glycosidase-F digestions 1067:1133 H 1094:1094 We probed the peptide acceptor specificities of the OSTs in vivo using a transgenic glycoprotein reporter system and performed glycoproteomics on endogenous parasite glycoproteins using sequential endoglycosidase H and peptide:N-glycosidase-F digestions. 28928222 3 90 theme cell 723:726 arg1 proteomics 736:745 cell culture proteomics 723:745 cell culture proteomics 723:745 Here, we show by blue-native gel electrophoresis and stable isotope labeling in cell culture proteomics that the TbSTT3A and TbSTT3B proteins associate with each other in large complexes that contain no other detectable protein subunits. 28928222 2 91 theme peptide 366:372 arg1 acceptor 374:381 different peptide acceptor and lipid-linked oligosaccharide donor specificities 356:434 acceptor 374:381 These OSTs have different peptide acceptor and lipid-linked oligosaccharide donor specificities, and trypanosomes do not follow many of the canonical rules developed for other eukaryotic N-glycosylation pathways, raising questions as to the basic architecture and detailed function of trypanosome OSTs. 28928222 8 92 contain has 1924:1926 arg1 eukaryote 1914:1922 a highly divergent eukaryote 1895:1922 a highly divergent eukaryote 1895:1922 Together, these studies provide insights into how a highly divergent eukaryote has re-wired protein N-glycosylation to provide protein sequence-specific N-glycan modifications. 28928222 8 92 contain has 1924:1926 arg2 N-glycosylation 1945:1959 re-wired protein N-glycosylation 1928:1959 re-wired protein N-glycosylation 1928:1959 Together, these studies provide insights into how a highly divergent eukaryote has re-wired protein N-glycosylation to provide protein sequence-specific N-glycan modifications. 28928222 2 93 theme oligosaccharide 400:414 arg1 specificities 422:434 different peptide acceptor and lipid-linked oligosaccharide donor specificities 356:434 specificities 422:434 These OSTs have different peptide acceptor and lipid-linked oligosaccharide donor specificities, and trypanosomes do not follow many of the canonical rules developed for other eukaryotic N-glycosylation pathways, raising questions as to the basic architecture and detailed function of trypanosome OSTs. 28928222 6 94 theme N-glycosylation 1642:1656 arg1 sites 1658:1662 all the putative N-glycosylation sites 1625:1662 all the putative N-glycosylation sites in the parasite proteome 1625:1687 Using machine learning, we assessed the features that best define TbSTT3A and TbSTT3B substrates in vivo and built an algorithm to predict the types of N-glycan most likely to predominate at all the putative N-glycosylation sites in the parasite proteome. 28928222 1 95 contain contains 184:191 arg1 brucei 142:147 Trypanosoma brucei 130:147 Trypanosoma brucei 130:147 Trypanosoma brucei causes African trypanosomiasis and contains three full-length oligosaccharyltransferase (OST) genes; two of which, TbSTT3A and TbSTT3B, are expressed in the bloodstream form of the parasite. 28928222 1 95 contain contains 184:191 arg2 genes 243:247 three full-length oligosaccharyltransferase (OST) genes 193:247 three full-length oligosaccharyltransferase (OST) genes 193:247 Trypanosoma brucei causes African trypanosomiasis and contains three full-length oligosaccharyltransferase (OST) genes; two of which, TbSTT3A and TbSTT3B, are expressed in the bloodstream form of the parasite. 28928222 2 96 theme rules 490:494 arg1 rules 490:494 the canonical rules 476:494 the canonical rules developed for other eukaryotic N-glycosylation pathways 476:550 These OSTs have different peptide acceptor and lipid-linked oligosaccharide donor specificities, and trypanosomes do not follow many of the canonical rules developed for other eukaryotic N-glycosylation pathways, raising questions as to the basic architecture and detailed function of trypanosome OSTs. 28928222 2 96 theme rules 490:494 arg1 many 468:471 many 468:471 many 468:471 These OSTs have different peptide acceptor and lipid-linked oligosaccharide donor specificities, and trypanosomes do not follow many of the canonical rules developed for other eukaryotic N-glycosylation pathways, raising questions as to the basic architecture and detailed function of trypanosome OSTs. 27015803 9 0 contain contain 1739:1745 arg2 donors 1776:1781 two distinct oligosaccharide donors 1747:1781 two distinct oligosaccharide donors for the oligosaccharyl transfer reaction 1747:1822 Our comprehensive study also revealed that one archaeal species could contain two distinct oligosaccharide donors for the oligosaccharyl transfer reaction. 27015803 9 0 contain contain 1739:1745 arg1 species 1725:1731 one archaeal species 1712:1731 one archaeal species 1712:1731 Our comprehensive study also revealed that one archaeal species could contain two distinct oligosaccharide donors for the oligosaccharyl transfer reaction. 27015803 10 1 contain contained 1847:1855 arg2 donors 1877:1882 two oligosaccharide donors 1857:1882 two oligosaccharide donors bearing oligosaccharide moieties with different backbone structures 1857:1950 The A. fulgidus cells contained two oligosaccharide donors bearing oligosaccharide moieties with different backbone structures, and the S. solfataricus cells contained two oligosaccharide donors bearing stereochemically different dolichol chains. 27015803 10 1 contain contained 1847:1855 arg1 cells 1841:1845 The A. fulgidus cells 1825:1845 The A. fulgidus cells 1825:1845 The A. fulgidus cells contained two oligosaccharide donors bearing oligosaccharide moieties with different backbone structures, and the S. solfataricus cells contained two oligosaccharide donors bearing stereochemically different dolichol chains. 27015803 1 2 theme predominant 171:181 arg1 modification 191:202 the predominant protein modification 167:202 the predominant protein modification in all three domains of life 167:231 The glycosylation of asparagine residues is the predominant protein modification in all three domains of life. 27015803 1 2 theme predominant 171:181 arg1 glycosylation 127:139 The glycosylation 123:139 The glycosylation of asparagine residues 123:162 The glycosylation of asparagine residues is the predominant protein modification in all three domains of life. 27015803 7 3 theme ionization 1233:1242 arg1 analyses 1269:1276 The electrospray ionization tandem mass spectrometry analyses 1216:1276 The electrospray ionization tandem mass spectrometry analyses 1216:1276 Here, we analyzed the donor structures of two species belonging to the phylum Crenarchaeota, Pyrobaculum calidifontis and Sulfolobus solfataricus, in addition to two species from the Euryarchaeota, Pyrococcus furiosus and Archaeoglobus fulgidus The electrospray ionization tandem mass spectrometry analyses confirmed that the two euryarchaeal oligosaccharide donors were the dolichol-monophosphate type and newly revealed that the two crenarchaeal oligosaccharide donors were the dolichol-diphosphate type. 27015803 5 4 theme dolichol-monophosphate 778:799 arg1 donors 806:811 the dolichol-monophosphate type donors 774:811 the dolichol-monophosphate type donors 774:811 Thus, the difference in the number of phosphate groups aroused interest in whether the use of the dolichol-monophosphate type donors is widespread in the domain Archaea. 27015803 5 5 theme groups 728:733 arg1 number 708:713 the number 704:713 the number of phosphate groups 704:733 Thus, the difference in the number of phosphate groups aroused interest in whether the use of the dolichol-monophosphate type donors is widespread in the domain Archaea. 27015803 1 6 theme protein 183:189 arg1 modification 191:202 the predominant protein modification 167:202 the predominant protein modification in all three domains of life 167:231 The glycosylation of asparagine residues is the predominant protein modification in all three domains of life. 27015803 1 6 theme protein 183:189 arg1 glycosylation 127:139 The glycosylation 123:139 The glycosylation of asparagine residues 123:162 The glycosylation of asparagine residues is the predominant protein modification in all three domains of life. 27015803 10 7 dep A. 1829:1830 arg1 fulgidus 1832:1839 fulgidus 1832:1839 fulgidus 1832:1839 The A. fulgidus cells contained two oligosaccharide donors bearing oligosaccharide moieties with different backbone structures, and the S. solfataricus cells contained two oligosaccharide donors bearing stereochemically different dolichol chains. 27015803 2 8 theme enzyme 377:382 arg1 action 350:355 the action 346:355 the action of a membrane-bound enzyme, oligosaccharyltransferase 346:409 An oligosaccharide chain is preassembled on a lipid-phospho carrier and transferred onto asparagine residues by the action of a membrane-bound enzyme, oligosaccharyltransferase. 27015803 6 9 theme phylum 949:954 arg1 Euryarchaeota 956:968 the phylum Euryarchaeota 945:968 the phylum Euryarchaeota 945:968 Currently, all of the archaeal species with identified oligosaccharide donors have belonged to the phylum Euryarchaeota. 27015803 8 10 theme Eukaryota 1552:1560 arg1 ancestor 1540:1547 the ancestor 1536:1547 the ancestor of Eukaryota 1536:1560 This novel finding is consistent with the hypothesis that the ancestor of Eukaryota is rooted within the TACK (Thaum-, Aig-, Cren-, and Korarchaeota) superphylum, which includes Crenarchaea. 27015803 8 11 theme TACK 1583:1586 arg1 superphylum 1628:1638 the TACK (Thaum-, Aig-, Cren-, and Korarchaeota) superphylum 1579:1638 the TACK (Thaum-, Aig-, Cren-, and Korarchaeota) superphylum 1579:1638 This novel finding is consistent with the hypothesis that the ancestor of Eukaryota is rooted within the TACK (Thaum-, Aig-, Cren-, and Korarchaeota) superphylum, which includes Crenarchaea. 27015803 0 12 theme Asn 104:106 arg1 Glycosylation 108:120 Asn Glycosylation 104:120 Asn Glycosylation 104:120 Comparative Analysis of Archaeal Lipid-linked Oligosaccharides That Serve as Oligosaccharide Donors for Asn Glycosylation. 27015803 5 13 theme donors 806:811 arg1 use 767:769 the use 763:769 the use of the dolichol-monophosphate type donors 763:811 Thus, the difference in the number of phosphate groups aroused interest in whether the use of the dolichol-monophosphate type donors is widespread in the domain Archaea. 27015803 5 13 theme donors 806:811 arg1 widespread 816:825 widespread 816:825 widespread 816:825 Thus, the difference in the number of phosphate groups aroused interest in whether the use of the dolichol-monophosphate type donors is widespread in the domain Archaea. 27015803 10 14 theme A. 1829:1830 arg1 cells 1841:1845 The A. fulgidus cells 1825:1845 The A. fulgidus cells 1825:1845 The A. fulgidus cells contained two oligosaccharide donors bearing oligosaccharide moieties with different backbone structures, and the S. solfataricus cells contained two oligosaccharide donors bearing stereochemically different dolichol chains. 27015803 9 15 theme archaeal 1716:1723 arg1 species 1725:1731 one archaeal species 1712:1731 one archaeal species 1712:1731 Our comprehensive study also revealed that one archaeal species could contain two distinct oligosaccharide donors for the oligosaccharyl transfer reaction. 27015803 7 16 theme donor 993:997 arg1 structures 999:1008 the donor structures 989:1008 the donor structures of two species belonging to the phylum Crenarchaeota, Pyrobaculum calidifontis and Sulfolobus solfataricus, 989:1116 Here, we analyzed the donor structures of two species belonging to the phylum Crenarchaeota, Pyrobaculum calidifontis and Sulfolobus solfataricus, in addition to two species from the Euryarchaeota, Pyrococcus furiosus and Archaeoglobus fulgidus The electrospray ionization tandem mass spectrometry analyses confirmed that the two euryarchaeal oligosaccharide donors were the dolichol-monophosphate type and newly revealed that the two crenarchaeal oligosaccharide donors were the dolichol-diphosphate type. 27015803 5 17 from Archaea 841:847 arg1 use 767:769 the use 763:769 the use of the dolichol-monophosphate type donors 763:811 Thus, the difference in the number of phosphate groups aroused interest in whether the use of the dolichol-monophosphate type donors is widespread in the domain Archaea. 27015803 5 17 from Archaea 841:847 arg1 widespread 816:825 widespread 816:825 widespread 816:825 Thus, the difference in the number of phosphate groups aroused interest in whether the use of the dolichol-monophosphate type donors is widespread in the domain Archaea. 27015803 9 18 theme comprehensive 1673:1685 arg1 study 1687:1691 Our comprehensive study 1669:1691 Our comprehensive study 1669:1691 Our comprehensive study also revealed that one archaeal species could contain two distinct oligosaccharide donors for the oligosaccharyl transfer reaction. 27015803 7 19 theme spectrometry 1256:1267 arg1 analyses 1269:1276 The electrospray ionization tandem mass spectrometry analyses 1216:1276 The electrospray ionization tandem mass spectrometry analyses 1216:1276 Here, we analyzed the donor structures of two species belonging to the phylum Crenarchaeota, Pyrobaculum calidifontis and Sulfolobus solfataricus, in addition to two species from the Euryarchaeota, Pyrococcus furiosus and Archaeoglobus fulgidus The electrospray ionization tandem mass spectrometry analyses confirmed that the two euryarchaeal oligosaccharide donors were the dolichol-monophosphate type and newly revealed that the two crenarchaeal oligosaccharide donors were the dolichol-diphosphate type. 27015803 10 20 theme different 2045:2053 arg1 chains 2064:2069 stereochemically different dolichol chains 2028:2069 stereochemically different dolichol chains 2028:2069 The A. fulgidus cells contained two oligosaccharide donors bearing oligosaccharide moieties with different backbone structures, and the S. solfataricus cells contained two oligosaccharide donors bearing stereochemically different dolichol chains. 27015803 7 21 theme oligosaccharide 1314:1328 arg1 donors 1330:1335 the two euryarchaeal oligosaccharide donors 1293:1335 the two euryarchaeal oligosaccharide donors 1293:1335 Here, we analyzed the donor structures of two species belonging to the phylum Crenarchaeota, Pyrobaculum calidifontis and Sulfolobus solfataricus, in addition to two species from the Euryarchaeota, Pyrococcus furiosus and Archaeoglobus fulgidus The electrospray ionization tandem mass spectrometry analyses confirmed that the two euryarchaeal oligosaccharide donors were the dolichol-monophosphate type and newly revealed that the two crenarchaeal oligosaccharide donors were the dolichol-diphosphate type. 27015803 7 21 theme oligosaccharide 1314:1328 arg1 type 1369:1372 the dolichol-monophosphate type 1342:1372 the dolichol-monophosphate type 1342:1372 Here, we analyzed the donor structures of two species belonging to the phylum Crenarchaeota, Pyrobaculum calidifontis and Sulfolobus solfataricus, in addition to two species from the Euryarchaeota, Pyrococcus furiosus and Archaeoglobus fulgidus The electrospray ionization tandem mass spectrometry analyses confirmed that the two euryarchaeal oligosaccharide donors were the dolichol-monophosphate type and newly revealed that the two crenarchaeal oligosaccharide donors were the dolichol-diphosphate type. 27015803 10 22 theme oligosaccharide 1892:1906 arg1 moieties 1908:1915 oligosaccharide moieties 1892:1915 oligosaccharide moieties 1892:1915 The A. fulgidus cells contained two oligosaccharide donors bearing oligosaccharide moieties with different backbone structures, and the S. solfataricus cells contained two oligosaccharide donors bearing stereochemically different dolichol chains. 27015803 0 23 theme Oligosaccharides 46:61 arg1 Analysis 12:19 Comparative Analysis 0:19 Comparative Analysis of Archaeal Lipid-linked Oligosaccharides That Serve as Oligosaccharide Donors for Asn Glycosylation 0:120 Comparative Analysis of Archaeal Lipid-linked Oligosaccharides That Serve as Oligosaccharide Donors for Asn Glycosylation. 27015803 9 24 theme distinct 1751:1758 arg1 donors 1776:1781 two distinct oligosaccharide donors 1747:1781 two distinct oligosaccharide donors for the oligosaccharyl transfer reaction 1747:1822 Our comprehensive study also revealed that one archaeal species could contain two distinct oligosaccharide donors for the oligosaccharyl transfer reaction. 27015803 8 25 dep TACK 1583:1586 arg1 Aig- 1597:1600 Aig- 1597:1600 Aig- 1597:1600 This novel finding is consistent with the hypothesis that the ancestor of Eukaryota is rooted within the TACK (Thaum-, Aig-, Cren-, and Korarchaeota) superphylum, which includes Crenarchaea. 27015803 8 25 dep TACK 1583:1586 arg1 Thaum- 1589:1594 Thaum- 1589:1594 Thaum- 1589:1594 This novel finding is consistent with the hypothesis that the ancestor of Eukaryota is rooted within the TACK (Thaum-, Aig-, Cren-, and Korarchaeota) superphylum, which includes Crenarchaea. 27015803 8 25 dep TACK 1583:1586 arg1 Cren- 1603:1607 Cren- 1603:1607 Cren- 1603:1607 This novel finding is consistent with the hypothesis that the ancestor of Eukaryota is rooted within the TACK (Thaum-, Aig-, Cren-, and Korarchaeota) superphylum, which includes Crenarchaea. 27015803 8 25 dep TACK 1583:1586 arg1 Korarchaeota 1614:1625 Korarchaeota 1614:1625 Korarchaeota 1614:1625 This novel finding is consistent with the hypothesis that the ancestor of Eukaryota is rooted within the TACK (Thaum-, Aig-, Cren-, and Korarchaeota) superphylum, which includes Crenarchaea. 27015803 9 26 dep contain 1739:1745 arg1 could 1733:1737 could 1733:1737 could 1733:1737 Our comprehensive study also revealed that one archaeal species could contain two distinct oligosaccharide donors for the oligosaccharyl transfer reaction. 27015803 7 27 theme crenarchaeal 1406:1417 arg1 type 1472:1475 the dolichol-diphosphate type 1447:1475 the dolichol-diphosphate type 1447:1475 Here, we analyzed the donor structures of two species belonging to the phylum Crenarchaeota, Pyrobaculum calidifontis and Sulfolobus solfataricus, in addition to two species from the Euryarchaeota, Pyrococcus furiosus and Archaeoglobus fulgidus The electrospray ionization tandem mass spectrometry analyses confirmed that the two euryarchaeal oligosaccharide donors were the dolichol-monophosphate type and newly revealed that the two crenarchaeal oligosaccharide donors were the dolichol-diphosphate type. 27015803 7 27 theme crenarchaeal 1406:1417 arg1 donors 1435:1440 the two crenarchaeal oligosaccharide donors 1398:1440 the two crenarchaeal oligosaccharide donors 1398:1440 Here, we analyzed the donor structures of two species belonging to the phylum Crenarchaeota, Pyrobaculum calidifontis and Sulfolobus solfataricus, in addition to two species from the Euryarchaeota, Pyrococcus furiosus and Archaeoglobus fulgidus The electrospray ionization tandem mass spectrometry analyses confirmed that the two euryarchaeal oligosaccharide donors were the dolichol-monophosphate type and newly revealed that the two crenarchaeal oligosaccharide donors were the dolichol-diphosphate type. 27015803 7 28 theme tandem 1244:1249 arg1 analyses 1269:1276 The electrospray ionization tandem mass spectrometry analyses 1216:1276 The electrospray ionization tandem mass spectrometry analyses 1216:1276 Here, we analyzed the donor structures of two species belonging to the phylum Crenarchaeota, Pyrobaculum calidifontis and Sulfolobus solfataricus, in addition to two species from the Euryarchaeota, Pyrococcus furiosus and Archaeoglobus fulgidus The electrospray ionization tandem mass spectrometry analyses confirmed that the two euryarchaeal oligosaccharide donors were the dolichol-monophosphate type and newly revealed that the two crenarchaeal oligosaccharide donors were the dolichol-diphosphate type. 27015803 7 29 theme oligosaccharide 1419:1433 arg1 type 1472:1475 the dolichol-diphosphate type 1447:1475 the dolichol-diphosphate type 1447:1475 Here, we analyzed the donor structures of two species belonging to the phylum Crenarchaeota, Pyrobaculum calidifontis and Sulfolobus solfataricus, in addition to two species from the Euryarchaeota, Pyrococcus furiosus and Archaeoglobus fulgidus The electrospray ionization tandem mass spectrometry analyses confirmed that the two euryarchaeal oligosaccharide donors were the dolichol-monophosphate type and newly revealed that the two crenarchaeal oligosaccharide donors were the dolichol-diphosphate type. 27015803 7 29 theme oligosaccharide 1419:1433 arg1 donors 1435:1440 the two crenarchaeal oligosaccharide donors 1398:1440 the two crenarchaeal oligosaccharide donors 1398:1440 Here, we analyzed the donor structures of two species belonging to the phylum Crenarchaeota, Pyrobaculum calidifontis and Sulfolobus solfataricus, in addition to two species from the Euryarchaeota, Pyrococcus furiosus and Archaeoglobus fulgidus The electrospray ionization tandem mass spectrometry analyses confirmed that the two euryarchaeal oligosaccharide donors were the dolichol-monophosphate type and newly revealed that the two crenarchaeal oligosaccharide donors were the dolichol-diphosphate type. 27015803 9 30 theme oligosaccharide 1760:1774 arg1 donors 1776:1781 two distinct oligosaccharide donors 1747:1781 two distinct oligosaccharide donors for the oligosaccharyl transfer reaction 1747:1822 Our comprehensive study also revealed that one archaeal species could contain two distinct oligosaccharide donors for the oligosaccharyl transfer reaction. 27015803 0 31 theme Comparative 0:10 arg1 Analysis 12:19 Comparative Analysis 0:19 Comparative Analysis of Archaeal Lipid-linked Oligosaccharides That Serve as Oligosaccharide Donors for Asn Glycosylation 0:120 Comparative Analysis of Archaeal Lipid-linked Oligosaccharides That Serve as Oligosaccharide Donors for Asn Glycosylation. 27015803 7 32 theme mass 1251:1254 arg1 analyses 1269:1276 The electrospray ionization tandem mass spectrometry analyses 1216:1276 The electrospray ionization tandem mass spectrometry analyses 1216:1276 Here, we analyzed the donor structures of two species belonging to the phylum Crenarchaeota, Pyrobaculum calidifontis and Sulfolobus solfataricus, in addition to two species from the Euryarchaeota, Pyrococcus furiosus and Archaeoglobus fulgidus The electrospray ionization tandem mass spectrometry analyses confirmed that the two euryarchaeal oligosaccharide donors were the dolichol-monophosphate type and newly revealed that the two crenarchaeal oligosaccharide donors were the dolichol-diphosphate type. 27015803 10 33 theme different 1922:1930 arg1 structures 1941:1950 different backbone structures 1922:1950 different backbone structures 1922:1950 The A. fulgidus cells contained two oligosaccharide donors bearing oligosaccharide moieties with different backbone structures, and the S. solfataricus cells contained two oligosaccharide donors bearing stereochemically different dolichol chains. 27015803 0 34 theme Archaeal 24:31 arg1 Donors 93:98 Oligosaccharide Donors 77:98 Oligosaccharide Donors for Asn Glycosylation 77:120 Comparative Analysis of Archaeal Lipid-linked Oligosaccharides That Serve as Oligosaccharide Donors for Asn Glycosylation. 27015803 0 34 theme Archaeal 24:31 arg1 Oligosaccharides 46:61 Archaeal Lipid-linked Oligosaccharides 24:61 Archaeal Lipid-linked Oligosaccharides That Serve as Oligosaccharide Donors for Asn Glycosylation 24:120 Comparative Analysis of Archaeal Lipid-linked Oligosaccharides That Serve as Oligosaccharide Donors for Asn Glycosylation. 27015803 7 35 dep fulgidus 1207:1214 arg1 confirmed 1278:1286 confirmed 1278:1286 confirmed that the two euryarchaeal oligosaccharide donors were the dolichol-monophosphate type and newly revealed that the two crenarchaeal oligosaccharide donors were the dolichol-diphosphate type 1278:1475 Here, we analyzed the donor structures of two species belonging to the phylum Crenarchaeota, Pyrobaculum calidifontis and Sulfolobus solfataricus, in addition to two species from the Euryarchaeota, Pyrococcus furiosus and Archaeoglobus fulgidus The electrospray ionization tandem mass spectrometry analyses confirmed that the two euryarchaeal oligosaccharide donors were the dolichol-monophosphate type and newly revealed that the two crenarchaeal oligosaccharide donors were the dolichol-diphosphate type. 27015803 5 36 theme domain 834:839 arg1 Archaea 841:847 the domain Archaea 830:847 the domain Archaea 830:847 Thus, the difference in the number of phosphate groups aroused interest in whether the use of the dolichol-monophosphate type donors is widespread in the domain Archaea. 27015803 0 37 link Lipid-linked 33:44 arg1 Donors 93:98 Oligosaccharide Donors 77:98 Oligosaccharide Donors for Asn Glycosylation 77:120 Comparative Analysis of Archaeal Lipid-linked Oligosaccharides That Serve as Oligosaccharide Donors for Asn Glycosylation. 27015803 0 37 link Lipid-linked 33:44 arg1 Oligosaccharides 46:61 Archaeal Lipid-linked Oligosaccharides 24:61 Archaeal Lipid-linked Oligosaccharides That Serve as Oligosaccharide Donors for Asn Glycosylation 24:120 Comparative Analysis of Archaeal Lipid-linked Oligosaccharides That Serve as Oligosaccharide Donors for Asn Glycosylation. 27015803 5 38 from difference 690:699 arg1 number 708:713 the number 704:713 the number of phosphate groups 704:733 Thus, the difference in the number of phosphate groups aroused interest in whether the use of the dolichol-monophosphate type donors is widespread in the domain Archaea. 27015803 3 39 theme oligosaccharide 416:430 arg1 donor 432:436 The oligosaccharide donor 412:436 The oligosaccharide donor for the oligosaccharyl transfer reaction 412:477 The oligosaccharide donor for the oligosaccharyl transfer reaction is dolichol-diphosphate-oligosaccharide in Eukaryota and polyprenol-diphosphate-oligosaccharide in Eubacteria. 27015803 3 39 theme oligosaccharide 416:430 arg1 dolichol-diphosphate-oligosaccharide 482:517 dolichol-diphosphate-oligosaccharide 482:517 dolichol-diphosphate-oligosaccharide in Eukaryota and polyprenol-diphosphate-oligosaccharide in Eubacteria 482:587 The oligosaccharide donor for the oligosaccharyl transfer reaction is dolichol-diphosphate-oligosaccharide in Eukaryota and polyprenol-diphosphate-oligosaccharide in Eubacteria. 27015803 1 40 gly glycosylation 127:139 arg1 residues 155:162 asparagine residues 144:162 asparagine residues 144:162 The glycosylation of asparagine residues is the predominant protein modification in all three domains of life. 27015803 2 41 theme asparagine 323:332 arg1 residues 334:341 asparagine residues 323:341 asparagine residues 323:341 An oligosaccharide chain is preassembled on a lipid-phospho carrier and transferred onto asparagine residues by the action of a membrane-bound enzyme, oligosaccharyltransferase. 27015803 10 42 theme solfataricus 1964:1975 arg1 cells 1977:1981 the S. solfataricus cells 1957:1981 the S. solfataricus cells 1957:1981 The A. fulgidus cells contained two oligosaccharide donors bearing oligosaccharide moieties with different backbone structures, and the S. solfataricus cells contained two oligosaccharide donors bearing stereochemically different dolichol chains. 27015803 3 43 theme transfer 461:468 arg1 reaction 470:477 the oligosaccharyl transfer reaction 442:477 the oligosaccharyl transfer reaction 442:477 The oligosaccharide donor for the oligosaccharyl transfer reaction is dolichol-diphosphate-oligosaccharide in Eukaryota and polyprenol-diphosphate-oligosaccharide in Eubacteria. 27015803 10 44 theme dolichol 2055:2062 arg1 chains 2064:2069 stereochemically different dolichol chains 2028:2069 stereochemically different dolichol chains 2028:2069 The A. fulgidus cells contained two oligosaccharide donors bearing oligosaccharide moieties with different backbone structures, and the S. solfataricus cells contained two oligosaccharide donors bearing stereochemically different dolichol chains. 27015803 7 45 from Euryarchaeota 1154:1166 arg1 species 1137:1143 two species 1133:1143 two species from the Euryarchaeota 1133:1166 Here, we analyzed the donor structures of two species belonging to the phylum Crenarchaeota, Pyrobaculum calidifontis and Sulfolobus solfataricus, in addition to two species from the Euryarchaeota, Pyrococcus furiosus and Archaeoglobus fulgidus The electrospray ionization tandem mass spectrometry analyses confirmed that the two euryarchaeal oligosaccharide donors were the dolichol-monophosphate type and newly revealed that the two crenarchaeal oligosaccharide donors were the dolichol-diphosphate type. 27015803 7 45 from Euryarchaeota 1154:1166 arg1 furiosus 1180:1187 Pyrococcus furiosus 1169:1187 Pyrococcus furiosus 1169:1187 Here, we analyzed the donor structures of two species belonging to the phylum Crenarchaeota, Pyrobaculum calidifontis and Sulfolobus solfataricus, in addition to two species from the Euryarchaeota, Pyrococcus furiosus and Archaeoglobus fulgidus The electrospray ionization tandem mass spectrometry analyses confirmed that the two euryarchaeal oligosaccharide donors were the dolichol-monophosphate type and newly revealed that the two crenarchaeal oligosaccharide donors were the dolichol-diphosphate type. 27015803 7 45 from Euryarchaeota 1154:1166 arg1 fulgidus 1207:1214 Archaeoglobus fulgidus 1193:1214 Archaeoglobus fulgidus The electrospray ionization tandem mass spectrometry analyses confirmed that the two euryarchaeal oligosaccharide donors were the dolichol-monophosphate type and newly revealed that the two crenarchaeal oligosaccharide donors were the dolichol-diphosphate type 1193:1475 Here, we analyzed the donor structures of two species belonging to the phylum Crenarchaeota, Pyrobaculum calidifontis and Sulfolobus solfataricus, in addition to two species from the Euryarchaeota, Pyrococcus furiosus and Archaeoglobus fulgidus The electrospray ionization tandem mass spectrometry analyses confirmed that the two euryarchaeal oligosaccharide donors were the dolichol-monophosphate type and newly revealed that the two crenarchaeal oligosaccharide donors were the dolichol-diphosphate type. 27015803 9 46 theme oligosaccharyl 1791:1804 arg1 reaction 1815:1822 the oligosaccharyl transfer reaction 1787:1822 the oligosaccharyl transfer reaction 1787:1822 Our comprehensive study also revealed that one archaeal species could contain two distinct oligosaccharide donors for the oligosaccharyl transfer reaction. 27015803 7 47 dep species 1137:1143 arg1 addition 1121:1128 addition 1121:1128 addition 1121:1128 Here, we analyzed the donor structures of two species belonging to the phylum Crenarchaeota, Pyrobaculum calidifontis and Sulfolobus solfataricus, in addition to two species from the Euryarchaeota, Pyrococcus furiosus and Archaeoglobus fulgidus The electrospray ionization tandem mass spectrometry analyses confirmed that the two euryarchaeal oligosaccharide donors were the dolichol-monophosphate type and newly revealed that the two crenarchaeal oligosaccharide donors were the dolichol-diphosphate type. 27015803 1 48 theme life 228:231 arg1 life 228:231 life 228:231 life 228:231 The glycosylation of asparagine residues is the predominant protein modification in all three domains of life. 27015803 1 48 theme life 228:231 arg1 domains 217:223 all three domains 207:223 all three domains of life 207:231 The glycosylation of asparagine residues is the predominant protein modification in all three domains of life. 27015803 0 49 theme Lipid-linked 33:44 arg1 Donors 93:98 Oligosaccharide Donors 77:98 Oligosaccharide Donors for Asn Glycosylation 77:120 Comparative Analysis of Archaeal Lipid-linked Oligosaccharides That Serve as Oligosaccharide Donors for Asn Glycosylation. 27015803 0 49 theme Lipid-linked 33:44 arg1 Oligosaccharides 46:61 Archaeal Lipid-linked Oligosaccharides 24:61 Archaeal Lipid-linked Oligosaccharides That Serve as Oligosaccharide Donors for Asn Glycosylation 24:120 Comparative Analysis of Archaeal Lipid-linked Oligosaccharides That Serve as Oligosaccharide Donors for Asn Glycosylation. 27015803 8 50 with consistent 1500:1509 arg1 hypothesis 1520:1529 the hypothesis that the ancestor of Eukaryota is rooted within the TACK (Thaum-, Aig-, Cren-, and Korarchaeota) superphylum, which includes Crenarchaea 1516:1666 the hypothesis that the ancestor of Eukaryota is rooted within the TACK (Thaum-, Aig-, Cren-, and Korarchaeota) superphylum, which includes Crenarchaea 1516:1666 This novel finding is consistent with the hypothesis that the ancestor of Eukaryota is rooted within the TACK (Thaum-, Aig-, Cren-, and Korarchaeota) superphylum, which includes Crenarchaea. 27015803 9 51 theme transfer 1806:1813 arg1 reaction 1815:1822 the oligosaccharyl transfer reaction 1787:1822 the oligosaccharyl transfer reaction 1787:1822 Our comprehensive study also revealed that one archaeal species could contain two distinct oligosaccharide donors for the oligosaccharyl transfer reaction. 27015803 6 52 theme identified 894:903 arg1 donors 921:926 identified oligosaccharide donors 894:926 identified oligosaccharide donors 894:926 Currently, all of the archaeal species with identified oligosaccharide donors have belonged to the phylum Euryarchaeota. 27015803 8 53 theme novel 1483:1487 arg1 finding 1489:1495 This novel finding 1478:1495 This novel finding 1478:1495 This novel finding is consistent with the hypothesis that the ancestor of Eukaryota is rooted within the TACK (Thaum-, Aig-, Cren-, and Korarchaeota) superphylum, which includes Crenarchaea. 27015803 7 54 theme euryarchaeal 1301:1312 arg1 donors 1330:1335 the two euryarchaeal oligosaccharide donors 1293:1335 the two euryarchaeal oligosaccharide donors 1293:1335 Here, we analyzed the donor structures of two species belonging to the phylum Crenarchaeota, Pyrobaculum calidifontis and Sulfolobus solfataricus, in addition to two species from the Euryarchaeota, Pyrococcus furiosus and Archaeoglobus fulgidus The electrospray ionization tandem mass spectrometry analyses confirmed that the two euryarchaeal oligosaccharide donors were the dolichol-monophosphate type and newly revealed that the two crenarchaeal oligosaccharide donors were the dolichol-diphosphate type. 27015803 7 54 theme euryarchaeal 1301:1312 arg1 type 1369:1372 the dolichol-monophosphate type 1342:1372 the dolichol-monophosphate type 1342:1372 Here, we analyzed the donor structures of two species belonging to the phylum Crenarchaeota, Pyrobaculum calidifontis and Sulfolobus solfataricus, in addition to two species from the Euryarchaeota, Pyrococcus furiosus and Archaeoglobus fulgidus The electrospray ionization tandem mass spectrometry analyses confirmed that the two euryarchaeal oligosaccharide donors were the dolichol-monophosphate type and newly revealed that the two crenarchaeal oligosaccharide donors were the dolichol-diphosphate type. 27015803 2 55 theme oligosaccharide 237:251 arg1 chain 253:257 An oligosaccharide chain 234:257 An oligosaccharide chain 234:257 An oligosaccharide chain is preassembled on a lipid-phospho carrier and transferred onto asparagine residues by the action of a membrane-bound enzyme, oligosaccharyltransferase. 27015803 6 56 theme oligosaccharide 905:919 arg1 donors 921:926 identified oligosaccharide donors 894:926 identified oligosaccharide donors 894:926 Currently, all of the archaeal species with identified oligosaccharide donors have belonged to the phylum Euryarchaeota. 27015803 2 57 theme membrane-bound 362:375 arg1 oligosaccharyltransferase 385:409 oligosaccharyltransferase 385:409 oligosaccharyltransferase 385:409 An oligosaccharide chain is preassembled on a lipid-phospho carrier and transferred onto asparagine residues by the action of a membrane-bound enzyme, oligosaccharyltransferase. 27015803 2 57 theme membrane-bound 362:375 arg1 enzyme 377:382 a membrane-bound enzyme 360:382 a membrane-bound enzyme 360:382 An oligosaccharide chain is preassembled on a lipid-phospho carrier and transferred onto asparagine residues by the action of a membrane-bound enzyme, oligosaccharyltransferase. 27015803 3 58 theme oligosaccharyl 446:459 arg1 reaction 470:477 the oligosaccharyl transfer reaction 442:477 the oligosaccharyl transfer reaction 442:477 The oligosaccharide donor for the oligosaccharyl transfer reaction is dolichol-diphosphate-oligosaccharide in Eukaryota and polyprenol-diphosphate-oligosaccharide in Eubacteria. 27015803 7 59 theme electrospray 1220:1231 arg1 analyses 1269:1276 The electrospray ionization tandem mass spectrometry analyses 1216:1276 The electrospray ionization tandem mass spectrometry analyses 1216:1276 Here, we analyzed the donor structures of two species belonging to the phylum Crenarchaeota, Pyrobaculum calidifontis and Sulfolobus solfataricus, in addition to two species from the Euryarchaeota, Pyrococcus furiosus and Archaeoglobus fulgidus The electrospray ionization tandem mass spectrometry analyses confirmed that the two euryarchaeal oligosaccharide donors were the dolichol-monophosphate type and newly revealed that the two crenarchaeal oligosaccharide donors were the dolichol-diphosphate type. 27015803 4 60 from donor 594:598 arg1 species 617:623 some archaeal species 603:623 some archaeal species 603:623 The donor in some archaeal species was reportedly dolichol-monophosphate-oligosaccharide. 27015803 5 61 theme type 801:804 arg1 donors 806:811 the dolichol-monophosphate type donors 774:811 the dolichol-monophosphate type donors 774:811 Thus, the difference in the number of phosphate groups aroused interest in whether the use of the dolichol-monophosphate type donors is widespread in the domain Archaea. 27015803 7 62 theme phylum 1042:1047 arg1 Crenarchaeota 1049:1061 the phylum Crenarchaeota 1038:1061 the phylum Crenarchaeota 1038:1061 Here, we analyzed the donor structures of two species belonging to the phylum Crenarchaeota, Pyrobaculum calidifontis and Sulfolobus solfataricus, in addition to two species from the Euryarchaeota, Pyrococcus furiosus and Archaeoglobus fulgidus The electrospray ionization tandem mass spectrometry analyses confirmed that the two euryarchaeal oligosaccharide donors were the dolichol-monophosphate type and newly revealed that the two crenarchaeal oligosaccharide donors were the dolichol-diphosphate type. 27015803 5 63 theme phosphate 718:726 arg1 groups 728:733 phosphate groups 718:733 phosphate groups 718:733 Thus, the difference in the number of phosphate groups aroused interest in whether the use of the dolichol-monophosphate type donors is widespread in the domain Archaea. 27015803 7 64 theme Pyrococcus 1169:1178 arg1 species 1137:1143 two species 1133:1143 two species from the Euryarchaeota 1133:1166 Here, we analyzed the donor structures of two species belonging to the phylum Crenarchaeota, Pyrobaculum calidifontis and Sulfolobus solfataricus, in addition to two species from the Euryarchaeota, Pyrococcus furiosus and Archaeoglobus fulgidus The electrospray ionization tandem mass spectrometry analyses confirmed that the two euryarchaeal oligosaccharide donors were the dolichol-monophosphate type and newly revealed that the two crenarchaeal oligosaccharide donors were the dolichol-diphosphate type. 27015803 7 64 theme Pyrococcus 1169:1178 arg1 furiosus 1180:1187 Pyrococcus furiosus 1169:1187 Pyrococcus furiosus 1169:1187 Here, we analyzed the donor structures of two species belonging to the phylum Crenarchaeota, Pyrobaculum calidifontis and Sulfolobus solfataricus, in addition to two species from the Euryarchaeota, Pyrococcus furiosus and Archaeoglobus fulgidus The electrospray ionization tandem mass spectrometry analyses confirmed that the two euryarchaeal oligosaccharide donors were the dolichol-monophosphate type and newly revealed that the two crenarchaeal oligosaccharide donors were the dolichol-diphosphate type. 27015803 2 65 theme lipid-phospho 280:292 arg1 carrier 294:300 a lipid-phospho carrier 278:300 a lipid-phospho carrier 278:300 An oligosaccharide chain is preassembled on a lipid-phospho carrier and transferred onto asparagine residues by the action of a membrane-bound enzyme, oligosaccharyltransferase. 27015803 6 66 theme archaeal 872:879 arg1 species 881:887 the archaeal species 868:887 the archaeal species 868:887 Currently, all of the archaeal species with identified oligosaccharide donors have belonged to the phylum Euryarchaeota. 27015803 1 67 theme asparagine 144:153 arg1 residues 155:162 asparagine residues 144:162 asparagine residues 144:162 The glycosylation of asparagine residues is the predominant protein modification in all three domains of life. 27015803 10 68 theme oligosaccharide 1997:2011 arg1 donors 2013:2018 two oligosaccharide donors 1993:2018 two oligosaccharide donors bearing stereochemically different dolichol chains 1993:2069 The A. fulgidus cells contained two oligosaccharide donors bearing oligosaccharide moieties with different backbone structures, and the S. solfataricus cells contained two oligosaccharide donors bearing stereochemically different dolichol chains. 27015803 1 69 theme residues 155:162 arg1 glycosylation 127:139 The glycosylation 123:139 The glycosylation of asparagine residues 123:162 The glycosylation of asparagine residues is the predominant protein modification in all three domains of life. 27015803 1 69 theme residues 155:162 arg1 modification 191:202 the predominant protein modification 167:202 the predominant protein modification in all three domains of life 167:231 The glycosylation of asparagine residues is the predominant protein modification in all three domains of life. 27015803 10 70 theme backbone 1932:1939 arg1 structures 1941:1950 different backbone structures 1922:1950 different backbone structures 1922:1950 The A. fulgidus cells contained two oligosaccharide donors bearing oligosaccharide moieties with different backbone structures, and the S. solfataricus cells contained two oligosaccharide donors bearing stereochemically different dolichol chains. 27015803 0 71 theme Oligosaccharide 77:91 arg1 Donors 93:98 Oligosaccharide Donors 77:98 Oligosaccharide Donors for Asn Glycosylation 77:120 Comparative Analysis of Archaeal Lipid-linked Oligosaccharides That Serve as Oligosaccharide Donors for Asn Glycosylation. 27015803 0 71 theme Oligosaccharide 77:91 arg1 Oligosaccharides 46:61 Archaeal Lipid-linked Oligosaccharides 24:61 Archaeal Lipid-linked Oligosaccharides That Serve as Oligosaccharide Donors for Asn Glycosylation 24:120 Comparative Analysis of Archaeal Lipid-linked Oligosaccharides That Serve as Oligosaccharide Donors for Asn Glycosylation. 27015803 3 72 from dolichol-diphosphate-oligosaccharide 482:517 arg1 polyprenol-diphosphate-oligosaccharide 536:573 polyprenol-diphosphate-oligosaccharide 536:573 polyprenol-diphosphate-oligosaccharide 536:573 The oligosaccharide donor for the oligosaccharyl transfer reaction is dolichol-diphosphate-oligosaccharide in Eukaryota and polyprenol-diphosphate-oligosaccharide in Eubacteria. 27015803 3 72 from dolichol-diphosphate-oligosaccharide 482:517 arg1 Eukaryota 522:530 Eukaryota 522:530 Eukaryota 522:530 The oligosaccharide donor for the oligosaccharyl transfer reaction is dolichol-diphosphate-oligosaccharide in Eukaryota and polyprenol-diphosphate-oligosaccharide in Eubacteria. 27015803 3 72 from dolichol-diphosphate-oligosaccharide 482:517 arg1 Eubacteria 578:587 Eubacteria 578:587 Eubacteria 578:587 The oligosaccharide donor for the oligosaccharyl transfer reaction is dolichol-diphosphate-oligosaccharide in Eukaryota and polyprenol-diphosphate-oligosaccharide in Eubacteria. 27015803 7 73 theme dolichol-diphosphate 1451:1470 arg1 type 1472:1475 the dolichol-diphosphate type 1447:1475 the dolichol-diphosphate type 1447:1475 Here, we analyzed the donor structures of two species belonging to the phylum Crenarchaeota, Pyrobaculum calidifontis and Sulfolobus solfataricus, in addition to two species from the Euryarchaeota, Pyrococcus furiosus and Archaeoglobus fulgidus The electrospray ionization tandem mass spectrometry analyses confirmed that the two euryarchaeal oligosaccharide donors were the dolichol-monophosphate type and newly revealed that the two crenarchaeal oligosaccharide donors were the dolichol-diphosphate type. 27015803 7 73 theme dolichol-diphosphate 1451:1470 arg1 donors 1435:1440 the two crenarchaeal oligosaccharide donors 1398:1440 the two crenarchaeal oligosaccharide donors 1398:1440 Here, we analyzed the donor structures of two species belonging to the phylum Crenarchaeota, Pyrobaculum calidifontis and Sulfolobus solfataricus, in addition to two species from the Euryarchaeota, Pyrococcus furiosus and Archaeoglobus fulgidus The electrospray ionization tandem mass spectrometry analyses confirmed that the two euryarchaeal oligosaccharide donors were the dolichol-monophosphate type and newly revealed that the two crenarchaeal oligosaccharide donors were the dolichol-diphosphate type. 27015803 10 74 theme oligosaccharide 1861:1875 arg1 donors 1877:1882 two oligosaccharide donors 1857:1882 two oligosaccharide donors bearing oligosaccharide moieties with different backbone structures 1857:1950 The A. fulgidus cells contained two oligosaccharide donors bearing oligosaccharide moieties with different backbone structures, and the S. solfataricus cells contained two oligosaccharide donors bearing stereochemically different dolichol chains. 27015803 10 75 contain contained 1983:1991 arg1 cells 1977:1981 the S. solfataricus cells 1957:1981 the S. solfataricus cells 1957:1981 The A. fulgidus cells contained two oligosaccharide donors bearing oligosaccharide moieties with different backbone structures, and the S. solfataricus cells contained two oligosaccharide donors bearing stereochemically different dolichol chains. 27015803 10 75 contain contained 1983:1991 arg2 donors 2013:2018 two oligosaccharide donors 1993:2018 two oligosaccharide donors bearing stereochemically different dolichol chains 1993:2069 The A. fulgidus cells contained two oligosaccharide donors bearing oligosaccharide moieties with different backbone structures, and the S. solfataricus cells contained two oligosaccharide donors bearing stereochemically different dolichol chains. 27015803 4 76 theme archaeal 608:615 arg1 species 617:623 some archaeal species 603:623 some archaeal species 603:623 The donor in some archaeal species was reportedly dolichol-monophosphate-oligosaccharide. 27015803 7 77 theme dolichol-monophosphate 1346:1367 arg1 donors 1330:1335 the two euryarchaeal oligosaccharide donors 1293:1335 the two euryarchaeal oligosaccharide donors 1293:1335 Here, we analyzed the donor structures of two species belonging to the phylum Crenarchaeota, Pyrobaculum calidifontis and Sulfolobus solfataricus, in addition to two species from the Euryarchaeota, Pyrococcus furiosus and Archaeoglobus fulgidus The electrospray ionization tandem mass spectrometry analyses confirmed that the two euryarchaeal oligosaccharide donors were the dolichol-monophosphate type and newly revealed that the two crenarchaeal oligosaccharide donors were the dolichol-diphosphate type. 27015803 7 77 theme dolichol-monophosphate 1346:1367 arg1 type 1369:1372 the dolichol-monophosphate type 1342:1372 the dolichol-monophosphate type 1342:1372 Here, we analyzed the donor structures of two species belonging to the phylum Crenarchaeota, Pyrobaculum calidifontis and Sulfolobus solfataricus, in addition to two species from the Euryarchaeota, Pyrococcus furiosus and Archaeoglobus fulgidus The electrospray ionization tandem mass spectrometry analyses confirmed that the two euryarchaeal oligosaccharide donors were the dolichol-monophosphate type and newly revealed that the two crenarchaeal oligosaccharide donors were the dolichol-diphosphate type. 27015803 1 78 from modification 191:202 arg1 life 228:231 life 228:231 life 228:231 The glycosylation of asparagine residues is the predominant protein modification in all three domains of life. 27015803 1 78 from modification 191:202 arg1 domains 217:223 all three domains 207:223 all three domains of life 207:231 The glycosylation of asparagine residues is the predominant protein modification in all three domains of life. 27015803 10 79 theme S. 1961:1962 arg1 cells 1977:1981 the S. solfataricus cells 1957:1981 the S. solfataricus cells 1957:1981 The A. fulgidus cells contained two oligosaccharide donors bearing oligosaccharide moieties with different backbone structures, and the S. solfataricus cells contained two oligosaccharide donors bearing stereochemically different dolichol chains. 27015803 7 80 theme species 1017:1023 arg1 structures 999:1008 the donor structures 989:1008 the donor structures of two species belonging to the phylum Crenarchaeota, Pyrobaculum calidifontis and Sulfolobus solfataricus, 989:1116 Here, we analyzed the donor structures of two species belonging to the phylum Crenarchaeota, Pyrobaculum calidifontis and Sulfolobus solfataricus, in addition to two species from the Euryarchaeota, Pyrococcus furiosus and Archaeoglobus fulgidus The electrospray ionization tandem mass spectrometry analyses confirmed that the two euryarchaeal oligosaccharide donors were the dolichol-monophosphate type and newly revealed that the two crenarchaeal oligosaccharide donors were the dolichol-diphosphate type. 27015803 5 81 from widespread 816:825 arg1 Archaea 841:847 the domain Archaea 830:847 the domain Archaea 830:847 Thus, the difference in the number of phosphate groups aroused interest in whether the use of the dolichol-monophosphate type donors is widespread in the domain Archaea. 25586188 11 0 theme N-glycan 1435:1442 arg1 degradation 1444:1454 N-glycan degradation 1435:1454 N-glycan degradation 1435:1454 This study constitutes the first evidence suggesting N-glycan degradation by a plant pathogen, a feature shared with human pathogenic bacteria. 25586188 11 1 theme pathogenic 1505:1514 arg1 bacteria 1516:1523 human pathogenic bacteria 1499:1523 human pathogenic bacteria 1499:1523 This study constitutes the first evidence suggesting N-glycan degradation by a plant pathogen, a feature shared with human pathogenic bacteria. 25586188 5 2 theme causal 431:436 arg1 agent 438:442 the causal agent 427:442 the causal agent of black rot disease of Brassica plants 427:482 campestris, the causal agent of black rot disease of Brassica plants, possesses a specific system for GlcNAc utilization expressed during host plant infection. 25586188 5 2 theme causal 431:436 arg1 campestris 415:424 campestris 415:424 campestris 415:424 campestris, the causal agent of black rot disease of Brassica plants, possesses a specific system for GlcNAc utilization expressed during host plant infection. 25586188 2 3 located found 227:231 arg2 carbohydrates 213:225 the carbohydrates 209:225 the carbohydrates found in plants 209:241 N-Glycans are widely distributed in living organisms but represent only a small fraction of the carbohydrates found in plants. 25586188 2 3 located found 227:231 arg1 plants 236:241 plants 236:241 plants 236:241 N-Glycans are widely distributed in living organisms but represent only a small fraction of the carbohydrates found in plants. 25586188 6 4 theme nixE 625:628 arg1 nixL 633:636 nixE to nixL 625:636 nixE to nixL 625:636 This system encompasses a cluster of eight genes (nixE to nixL) encoding glycoside hydrolases (GHs). 25586188 6 4 theme nixE 625:628 arg1 genes 618:622 eight genes 612:622 eight genes (nixE to nixL) encoding glycoside hydrolases (GHs) 612:673 This system encompasses a cluster of eight genes (nixE to nixL) encoding glycoside hydrolases (GHs). 25586188 12 5 theme life 1666:1669 arg1 cycle 1671:1675 their life cycle 1660:1675 their life cycle 1660:1675 Plant N-glycans should therefore be included in the repertoire of molecules putatively metabolized by phytopathogenic bacteria during their life cycle. 25586188 4 6 dep pv 411:412 arg1 campestris 400:409 Xanthomonas campestris 388:409 Xanthomonas campestris 388:409 Xanthomonas campestris pv. 25586188 3 7 theme plant 371:375 arg1 infection 377:385 plant infection 371:385 plant infection 371:385 This probably explains why they have not previously been considered as substrates exploited by phytopathogenic bacteria during plant infection. 25586188 2 8 theme living 153:158 arg1 organisms 160:168 living organisms 153:168 living organisms 153:168 N-Glycans are widely distributed in living organisms but represent only a small fraction of the carbohydrates found in plants. 25586188 8 9 theme α-mannosidase 987:999 arg1 GH92 1007:1010 GH92 1007:1010 GH92 1007:1010 The removal of the α-1,3-mannose by the α-mannosidase NixK (GH92) is a prerequisite for the subsequent action of the β-xylosidase NixI (GH3), which is involved in the cleavage of the β-1,2-xylose, followed by the α-mannosidase NixJ (GH125), which removes the α-1,6-mannose. 25586188 8 9 theme α-mannosidase 987:999 arg1 NixK 1001:1004 the α-mannosidase NixK 983:1004 the α-mannosidase NixK (GH92) 983:1011 The removal of the α-1,3-mannose by the α-mannosidase NixK (GH92) is a prerequisite for the subsequent action of the β-xylosidase NixI (GH3), which is involved in the cleavage of the β-1,2-xylose, followed by the α-mannosidase NixJ (GH125), which removes the α-1,6-mannose. 25586188 3 10 theme phytopathogenic 339:353 arg1 bacteria 355:362 phytopathogenic bacteria 339:362 phytopathogenic bacteria 339:362 This probably explains why they have not previously been considered as substrates exploited by phytopathogenic bacteria during plant infection. 25586188 7 11 gly N-glycopeptide 840:853 arg2 N-glycopeptide 840:853 a N-glycopeptide 838:853 a N-glycopeptide containing two GlcNAcs, three mannoses, one fucose, and one xylose (N2M3FX) as a substrate 838:944 In this paper, we have characterized the enzymatic activities of these GHs and demonstrated their involvement in sequential degradation of a plant N-glycan using a N-glycopeptide containing two GlcNAcs, three mannoses, one fucose, and one xylose (N2M3FX) as a substrate. 25586188 7 12 from involvement 774:784 arg1 degradation 800:810 sequential degradation 789:810 sequential degradation of a plant N-glycan using a N-glycopeptide containing two GlcNAcs, three mannoses, one fucose, and one xylose (N2M3FX) as a substrate 789:944 In this paper, we have characterized the enzymatic activities of these GHs and demonstrated their involvement in sequential degradation of a plant N-glycan using a N-glycopeptide containing two GlcNAcs, three mannoses, one fucose, and one xylose (N2M3FX) as a substrate. 25586188 9 13 theme campestris 1355:1364 arg1 pv 1366:1367 X. campestris pv 1352:1367 X. campestris pv 1352:1367 These data, combined to the subcellular localization of the enzymes, allowed us to propose a model of N-glycopeptide processing by X. campestris pv. 25586188 5 14 theme specific 497:504 arg1 system 506:511 a specific system 495:511 a specific system for GlcNAc utilization expressed during host plant infection 495:572 campestris, the causal agent of black rot disease of Brassica plants, possesses a specific system for GlcNAc utilization expressed during host plant infection. 25586188 0 15 from campestris 38:47 arg1 cluster 13:19 The N-Glycan cluster 0:19 The N-Glycan cluster from Xanthomonas campestris 0:47 The N-Glycan cluster from Xanthomonas campestris pv. 25586188 9 16 theme N-glycopeptide 1323:1336 arg1 processing 1338:1347 N-glycopeptide processing 1323:1347 N-glycopeptide processing by X. campestris pv 1323:1367 These data, combined to the subcellular localization of the enzymes, allowed us to propose a model of N-glycopeptide processing by X. campestris pv. 25586188 0 17 theme N-Glycan 4:11 arg1 cluster 13:19 The N-Glycan cluster 0:19 The N-Glycan cluster from Xanthomonas campestris 0:47 The N-Glycan cluster from Xanthomonas campestris pv. 25586188 5 18 contain possesses 485:493 arg1 agent 438:442 the causal agent 427:442 the causal agent of black rot disease of Brassica plants 427:482 campestris, the causal agent of black rot disease of Brassica plants, possesses a specific system for GlcNAc utilization expressed during host plant infection. 25586188 5 18 contain possesses 485:493 arg2 system 506:511 a specific system 495:511 a specific system for GlcNAc utilization expressed during host plant infection 495:572 campestris, the causal agent of black rot disease of Brassica plants, possesses a specific system for GlcNAc utilization expressed during host plant infection. 25586188 5 18 contain possesses 485:493 arg1 campestris 415:424 campestris 415:424 campestris 415:424 campestris, the causal agent of black rot disease of Brassica plants, possesses a specific system for GlcNAc utilization expressed during host plant infection. 25586188 8 19 theme α-mannosidase 1160:1172 arg1 GH125 1180:1184 GH125 1180:1184 GH125 1180:1184 The removal of the α-1,3-mannose by the α-mannosidase NixK (GH92) is a prerequisite for the subsequent action of the β-xylosidase NixI (GH3), which is involved in the cleavage of the β-1,2-xylose, followed by the α-mannosidase NixJ (GH125), which removes the α-1,6-mannose. 25586188 8 19 theme α-mannosidase 1160:1172 arg1 NixJ 1174:1177 the α-mannosidase NixJ 1156:1177 the α-mannosidase NixJ (GH125) 1156:1185 The removal of the α-1,3-mannose by the α-mannosidase NixK (GH92) is a prerequisite for the subsequent action of the β-xylosidase NixI (GH3), which is involved in the cleavage of the β-1,2-xylose, followed by the α-mannosidase NixJ (GH125), which removes the α-1,6-mannose. 25586188 7 20 theme sequential 789:798 arg1 degradation 800:810 sequential degradation 789:810 sequential degradation of a plant N-glycan using a N-glycopeptide containing two GlcNAcs, three mannoses, one fucose, and one xylose (N2M3FX) as a substrate 789:944 In this paper, we have characterized the enzymatic activities of these GHs and demonstrated their involvement in sequential degradation of a plant N-glycan using a N-glycopeptide containing two GlcNAcs, three mannoses, one fucose, and one xylose (N2M3FX) as a substrate. 25586188 8 21 theme α-1,3-mannose 966:978 arg1 prerequisite 1018:1029 a prerequisite 1016:1029 a prerequisite for the subsequent action of the β-xylosidase NixI (GH3), which is involved in the cleavage of the β-1,2-xylose, followed by the α-mannosidase NixJ (GH125), which removes the α-1,6-mannose 1016:1218 The removal of the α-1,3-mannose by the α-mannosidase NixK (GH92) is a prerequisite for the subsequent action of the β-xylosidase NixI (GH3), which is involved in the cleavage of the β-1,2-xylose, followed by the α-mannosidase NixJ (GH125), which removes the α-1,6-mannose. 25586188 8 21 theme α-1,3-mannose 966:978 arg1 removal 951:957 The removal 947:957 The removal of the α-1,3-mannose by the α-mannosidase NixK (GH92) 947:1011 The removal of the α-1,3-mannose by the α-mannosidase NixK (GH92) is a prerequisite for the subsequent action of the β-xylosidase NixI (GH3), which is involved in the cleavage of the β-1,2-xylose, followed by the α-mannosidase NixJ (GH125), which removes the α-1,6-mannose. 25586188 1 22 theme sequential 79:88 arg1 processing 105:114 sequential plant N-glycan processing 79:114 sequential plant N-glycan processing 79:114 campestris: a toolbox for sequential plant N-glycan processing. 25586188 5 23 theme Brassica 468:475 arg1 plants 477:482 Brassica plants 468:482 Brassica plants 468:482 campestris, the causal agent of black rot disease of Brassica plants, possesses a specific system for GlcNAc utilization expressed during host plant infection. 25586188 12 24 theme Plant 1526:1530 arg1 N-glycans 1532:1540 Plant N-glycans 1526:1540 Plant N-glycans 1526:1540 Plant N-glycans should therefore be included in the repertoire of molecules putatively metabolized by phytopathogenic bacteria during their life cycle. 25586188 4 25 theme Xanthomonas 388:398 arg1 campestris 400:409 Xanthomonas campestris 388:409 Xanthomonas campestris 388:409 Xanthomonas campestris pv. 25586188 1 26 theme plant 90:94 arg1 processing 105:114 sequential plant N-glycan processing 79:114 sequential plant N-glycan processing 79:114 campestris: a toolbox for sequential plant N-glycan processing. 25586188 5 27 theme plants 477:482 arg1 disease 457:463 black rot disease 447:463 black rot disease of Brassica plants 447:482 campestris, the causal agent of black rot disease of Brassica plants, possesses a specific system for GlcNAc utilization expressed during host plant infection. 25586188 9 28 theme X. 1352:1353 arg1 pv 1366:1367 X. campestris pv 1352:1367 X. campestris pv 1352:1367 These data, combined to the subcellular localization of the enzymes, allowed us to propose a model of N-glycopeptide processing by X. campestris pv. 25586188 9 29 gly N-glycopeptide 1323:1336 arg2 N-glycopeptide 1323:1336 N-glycopeptide processing 1323:1347 N-glycopeptide processing by X. campestris pv 1323:1367 These data, combined to the subcellular localization of the enzymes, allowed us to propose a model of N-glycopeptide processing by X. campestris pv. 25586188 1 30 theme N-glycan 96:103 arg1 processing 105:114 sequential plant N-glycan processing 79:114 sequential plant N-glycan processing 79:114 campestris: a toolbox for sequential plant N-glycan processing. 25586188 7 31 theme plant 817:821 arg1 N-glycan 823:830 a plant N-glycan 815:830 a plant N-glycan using a N-glycopeptide containing two GlcNAcs, three mannoses, one fucose, and one xylose (N2M3FX) as a substrate 815:944 In this paper, we have characterized the enzymatic activities of these GHs and demonstrated their involvement in sequential degradation of a plant N-glycan using a N-glycopeptide containing two GlcNAcs, three mannoses, one fucose, and one xylose (N2M3FX) as a substrate. 25586188 12 32 theme phytopathogenic 1628:1642 arg1 bacteria 1644:1651 phytopathogenic bacteria 1628:1651 phytopathogenic bacteria 1628:1651 Plant N-glycans should therefore be included in the repertoire of molecules putatively metabolized by phytopathogenic bacteria during their life cycle. 25586188 0 33 theme Xanthomonas 26:36 arg1 campestris 38:47 Xanthomonas campestris 26:47 Xanthomonas campestris 26:47 The N-Glycan cluster from Xanthomonas campestris pv. 25586188 9 34 theme subcellular 1249:1259 arg1 localization 1261:1272 the subcellular localization 1245:1272 the subcellular localization of the enzymes 1245:1287 These data, combined to the subcellular localization of the enzymes, allowed us to propose a model of N-glycopeptide processing by X. campestris pv. 25586188 5 35 theme host 553:556 arg1 infection 564:572 host plant infection 553:572 host plant infection 553:572 campestris, the causal agent of black rot disease of Brassica plants, possesses a specific system for GlcNAc utilization expressed during host plant infection. 25586188 2 36 theme carbohydrates 213:225 arg1 fraction 197:204 only a small fraction 184:204 only a small fraction of the carbohydrates found in plants 184:241 N-Glycans are widely distributed in living organisms but represent only a small fraction of the carbohydrates found in plants. 25586188 5 37 theme plant 558:562 arg1 infection 564:572 host plant infection 553:572 host plant infection 553:572 campestris, the causal agent of black rot disease of Brassica plants, possesses a specific system for GlcNAc utilization expressed during host plant infection. 25586188 8 38 theme β-1,2-xylose 1130:1141 arg1 cleavage 1114:1121 the cleavage 1110:1121 the cleavage of the β-1,2-xylose, followed by the α-mannosidase NixJ (GH125), which removes the α-1,6-mannose 1110:1218 The removal of the α-1,3-mannose by the α-mannosidase NixK (GH92) is a prerequisite for the subsequent action of the β-xylosidase NixI (GH3), which is involved in the cleavage of the β-1,2-xylose, followed by the α-mannosidase NixJ (GH125), which removes the α-1,6-mannose. 25586188 7 39 theme GHs 747:749 arg1 activities 727:736 the enzymatic activities 713:736 the enzymatic activities of these GHs 713:749 In this paper, we have characterized the enzymatic activities of these GHs and demonstrated their involvement in sequential degradation of a plant N-glycan using a N-glycopeptide containing two GlcNAcs, three mannoses, one fucose, and one xylose (N2M3FX) as a substrate. 25586188 8 40 theme subsequent 1039:1048 arg1 action 1050:1055 the subsequent action 1035:1055 the subsequent action of the β-xylosidase NixI (GH3), which is involved in the cleavage of the β-1,2-xylose, followed by the α-mannosidase NixJ (GH125), which removes the α-1,6-mannose 1035:1218 The removal of the α-1,3-mannose by the α-mannosidase NixK (GH92) is a prerequisite for the subsequent action of the β-xylosidase NixI (GH3), which is involved in the cleavage of the β-1,2-xylose, followed by the α-mannosidase NixJ (GH125), which removes the α-1,6-mannose. 25586188 6 41 dep nixL 633:636 arg1 to 630:631 to 630:631 to 630:631 This system encompasses a cluster of eight genes (nixE to nixL) encoding glycoside hydrolases (GHs). 25586188 5 42 theme black 447:451 arg1 disease 457:463 black rot disease 447:463 black rot disease of Brassica plants 447:482 campestris, the causal agent of black rot disease of Brassica plants, possesses a specific system for GlcNAc utilization expressed during host plant infection. 25586188 11 43 theme plant 1461:1465 arg1 pathogen 1467:1474 a plant pathogen 1459:1474 a plant pathogen 1459:1474 This study constitutes the first evidence suggesting N-glycan degradation by a plant pathogen, a feature shared with human pathogenic bacteria. 25586188 11 43 theme plant 1461:1465 arg1 feature 1479:1485 a feature 1477:1485 a feature shared with human pathogenic bacteria 1477:1523 This study constitutes the first evidence suggesting N-glycan degradation by a plant pathogen, a feature shared with human pathogenic bacteria. 25586188 7 44 contain containing 855:864 arg2 xylose 915:920 one xylose 911:920 one xylose (N2M3FX) 911:929 In this paper, we have characterized the enzymatic activities of these GHs and demonstrated their involvement in sequential degradation of a plant N-glycan using a N-glycopeptide containing two GlcNAcs, three mannoses, one fucose, and one xylose (N2M3FX) as a substrate. 25586188 7 44 contain containing 855:864 arg2 mannoses 885:892 three mannoses 879:892 three mannoses 879:892 In this paper, we have characterized the enzymatic activities of these GHs and demonstrated their involvement in sequential degradation of a plant N-glycan using a N-glycopeptide containing two GlcNAcs, three mannoses, one fucose, and one xylose (N2M3FX) as a substrate. 25586188 7 44 contain containing 855:864 arg2 substrate 936:944 a substrate 934:944 a substrate 934:944 In this paper, we have characterized the enzymatic activities of these GHs and demonstrated their involvement in sequential degradation of a plant N-glycan using a N-glycopeptide containing two GlcNAcs, three mannoses, one fucose, and one xylose (N2M3FX) as a substrate. 25586188 7 44 contain containing 855:864 arg2 fucose 899:904 one fucose 895:904 one fucose 895:904 In this paper, we have characterized the enzymatic activities of these GHs and demonstrated their involvement in sequential degradation of a plant N-glycan using a N-glycopeptide containing two GlcNAcs, three mannoses, one fucose, and one xylose (N2M3FX) as a substrate. 25586188 7 44 contain containing 855:864 arg2 N2M3FX 923:928 N2M3FX 923:928 N2M3FX 923:928 In this paper, we have characterized the enzymatic activities of these GHs and demonstrated their involvement in sequential degradation of a plant N-glycan using a N-glycopeptide containing two GlcNAcs, three mannoses, one fucose, and one xylose (N2M3FX) as a substrate. 25586188 7 44 contain containing 855:864 arg1 N-glycopeptide 840:853 a N-glycopeptide 838:853 a N-glycopeptide containing two GlcNAcs, three mannoses, one fucose, and one xylose (N2M3FX) as a substrate 838:944 In this paper, we have characterized the enzymatic activities of these GHs and demonstrated their involvement in sequential degradation of a plant N-glycan using a N-glycopeptide containing two GlcNAcs, three mannoses, one fucose, and one xylose (N2M3FX) as a substrate. 25586188 7 44 contain containing 855:864 arg2 GlcNAcs 870:876 two GlcNAcs 866:876 two GlcNAcs 866:876 In this paper, we have characterized the enzymatic activities of these GHs and demonstrated their involvement in sequential degradation of a plant N-glycan using a N-glycopeptide containing two GlcNAcs, three mannoses, one fucose, and one xylose (N2M3FX) as a substrate. 25586188 1 45 dep campestris 53:62 arg1 toolbox 67:73 a toolbox 65:73 campestris: a toolbox for sequential plant N-glycan processing. 53:115 campestris: a toolbox for sequential plant N-glycan processing. 25586188 5 46 theme rot 453:455 arg1 disease 457:463 black rot disease 447:463 black rot disease of Brassica plants 447:482 campestris, the causal agent of black rot disease of Brassica plants, possesses a specific system for GlcNAc utilization expressed during host plant infection. 25586188 9 47 theme enzymes 1281:1287 arg1 localization 1261:1272 the subcellular localization 1245:1272 the subcellular localization of the enzymes 1245:1287 These data, combined to the subcellular localization of the enzymes, allowed us to propose a model of N-glycopeptide processing by X. campestris pv. 25586188 2 48 theme small 191:195 arg1 fraction 197:204 only a small fraction 184:204 only a small fraction of the carbohydrates found in plants 184:241 N-Glycans are widely distributed in living organisms but represent only a small fraction of the carbohydrates found in plants. 25586188 5 49 theme GlcNAc 517:522 arg1 utilization 524:534 GlcNAc utilization 517:534 GlcNAc utilization expressed during host plant infection 517:572 campestris, the causal agent of black rot disease of Brassica plants, possesses a specific system for GlcNAc utilization expressed during host plant infection. 25586188 7 50 theme N-glycan 823:830 arg1 degradation 800:810 sequential degradation 789:810 sequential degradation of a plant N-glycan using a N-glycopeptide containing two GlcNAcs, three mannoses, one fucose, and one xylose (N2M3FX) as a substrate 789:944 In this paper, we have characterized the enzymatic activities of these GHs and demonstrated their involvement in sequential degradation of a plant N-glycan using a N-glycopeptide containing two GlcNAcs, three mannoses, one fucose, and one xylose (N2M3FX) as a substrate. 25586188 5 51 theme disease 457:463 arg1 agent 438:442 the causal agent 427:442 the causal agent of black rot disease of Brassica plants 427:482 campestris, the causal agent of black rot disease of Brassica plants, possesses a specific system for GlcNAc utilization expressed during host plant infection. 25586188 5 51 theme disease 457:463 arg1 campestris 415:424 campestris 415:424 campestris 415:424 campestris, the causal agent of black rot disease of Brassica plants, possesses a specific system for GlcNAc utilization expressed during host plant infection. 25586188 8 52 theme NixI 1077:1080 arg1 action 1050:1055 the subsequent action 1035:1055 the subsequent action of the β-xylosidase NixI (GH3), which is involved in the cleavage of the β-1,2-xylose, followed by the α-mannosidase NixJ (GH125), which removes the α-1,6-mannose 1035:1218 The removal of the α-1,3-mannose by the α-mannosidase NixK (GH92) is a prerequisite for the subsequent action of the β-xylosidase NixI (GH3), which is involved in the cleavage of the β-1,2-xylose, followed by the α-mannosidase NixJ (GH125), which removes the α-1,6-mannose. 25586188 12 53 theme molecules 1592:1600 arg1 molecules 1592:1600 molecules 1592:1600 molecules putatively metabolized by phytopathogenic bacteria during their life cycle 1592:1675 Plant N-glycans should therefore be included in the repertoire of molecules putatively metabolized by phytopathogenic bacteria during their life cycle. 25586188 12 53 theme molecules 1592:1600 arg1 repertoire 1578:1587 the repertoire 1574:1587 the repertoire of molecules putatively metabolized by phytopathogenic bacteria during their life cycle 1574:1675 Plant N-glycans should therefore be included in the repertoire of molecules putatively metabolized by phytopathogenic bacteria during their life cycle. 25586188 6 54 theme glycoside 648:656 arg1 GHs 670:672 GHs 670:672 GHs 670:672 This system encompasses a cluster of eight genes (nixE to nixL) encoding glycoside hydrolases (GHs). 25586188 6 54 theme glycoside 648:656 arg1 hydrolases 658:667 glycoside hydrolases 648:667 glycoside hydrolases (GHs) 648:673 This system encompasses a cluster of eight genes (nixE to nixL) encoding glycoside hydrolases (GHs). 25586188 7 55 theme enzymatic 717:725 arg1 activities 727:736 the enzymatic activities 713:736 the enzymatic activities of these GHs 713:749 In this paper, we have characterized the enzymatic activities of these GHs and demonstrated their involvement in sequential degradation of a plant N-glycan using a N-glycopeptide containing two GlcNAcs, three mannoses, one fucose, and one xylose (N2M3FX) as a substrate. 25586188 8 56 theme β-xylosidase 1064:1075 arg1 GH3 1083:1085 GH3 1083:1085 GH3 1083:1085 The removal of the α-1,3-mannose by the α-mannosidase NixK (GH92) is a prerequisite for the subsequent action of the β-xylosidase NixI (GH3), which is involved in the cleavage of the β-1,2-xylose, followed by the α-mannosidase NixJ (GH125), which removes the α-1,6-mannose. 25586188 8 56 theme β-xylosidase 1064:1075 arg1 NixI 1077:1080 the β-xylosidase NixI 1060:1080 the β-xylosidase NixI (GH3) 1060:1086 The removal of the α-1,3-mannose by the α-mannosidase NixK (GH92) is a prerequisite for the subsequent action of the β-xylosidase NixI (GH3), which is involved in the cleavage of the β-1,2-xylose, followed by the α-mannosidase NixJ (GH125), which removes the α-1,6-mannose. 25586188 9 57 theme processing 1338:1347 arg1 model 1314:1318 a model 1312:1318 a model of N-glycopeptide processing by X. campestris pv 1312:1367 These data, combined to the subcellular localization of the enzymes, allowed us to propose a model of N-glycopeptide processing by X. campestris pv. 25586188 11 58 theme human 1499:1503 arg1 bacteria 1516:1523 human pathogenic bacteria 1499:1523 human pathogenic bacteria 1499:1523 This study constitutes the first evidence suggesting N-glycan degradation by a plant pathogen, a feature shared with human pathogenic bacteria. 25586188 6 59 theme genes 618:622 arg1 cluster 601:607 a cluster 599:607 a cluster of eight genes (nixE to nixL) encoding glycoside hydrolases (GHs) 599:673 This system encompasses a cluster of eight genes (nixE to nixL) encoding glycoside hydrolases (GHs). 25586188 11 60 theme first 1409:1413 arg1 evidence 1415:1422 the first evidence 1405:1422 the first evidence suggesting N-glycan degradation by a plant pathogen, a feature shared with human pathogenic bacteria 1405:1523 This study constitutes the first evidence suggesting N-glycan degradation by a plant pathogen, a feature shared with human pathogenic bacteria. 26675134 0 0 theme Possible 79:86 arg1 implications 101:112 Possible haemorrhagic implications 79:112 Possible haemorrhagic implications 79:112 Variation of fibrinogen oligosaccharide structure in the acute phase response: Possible haemorrhagic implications. 26675134 4 1 theme samples 523:529 arg1 series 506:511 A series 504:511 METHODS A series of plasma samples 496:529 METHODS A series of plasma samples was obtained from two individuals suffering an acute phase response. 26675134 6 2 theme γ 757:757 arg1 chains 759:764 The Bβ and γ chains 746:764 RESULTS The Bβ and γ chains of acute phase fibrinogen 738:790 RESULTS The Bβ and γ chains of acute phase fibrinogen showed a mass decrease of 162 Da (Gal) in some 50% of the molecules, and the Bβ chain showed an additional decrease corresponding to a further loss of NAcGlc. 26675134 5 3 with digestion 683:691 arg1 galactosidase 723:735 β1,4 galactosidase 718:735 β1,4 galactosidase 718:735 Fibrinogen chains were examined directly by ESI mass spectrometry before and after digestion with N-glycosidase F and β1,4 galactosidase. 26675134 5 3 with digestion 683:691 arg1 F 712:712 N-glycosidase F 698:712 N-glycosidase F 698:712 Fibrinogen chains were examined directly by ESI mass spectrometry before and after digestion with N-glycosidase F and β1,4 galactosidase. 26675134 4 4 dep METHODS 496:502 arg1 series 506:511 A series 504:511 METHODS A series of plasma samples 496:529 METHODS A series of plasma samples was obtained from two individuals suffering an acute phase response. 26675134 8 5 theme galactosidase 1130:1142 arg1 treatment 1144:1152 β1,4 galactosidase treatment 1125:1152 β1,4 galactosidase treatment 1125:1152 β1,4 galactosidase treatment showed the structural difference was the absence of the penultimate Gal from the biantennary oligosaccharides, and mapping of tryptic glycopeptides confirmed these results showing that approximately half the chains lacked Gal. 26675134 6 6 theme additional 888:897 arg1 decrease 899:906 an additional decrease 885:906 an additional decrease corresponding to a further loss of NAcGlc 885:948 RESULTS The Bβ and γ chains of acute phase fibrinogen showed a mass decrease of 162 Da (Gal) in some 50% of the molecules, and the Bβ chain showed an additional decrease corresponding to a further loss of NAcGlc. 26675134 7 7 theme heterogeneity 1110:1122 arg1 oligosaccharide 1077:1091 the N-linked oligosaccharide 1064:1091 the N-linked oligosaccharide 1064:1091 Incubation with N-glycosidase F normalised all isoform masses to that of the quiescent naked protein, confirming the N-linked oligosaccharide as the source of heterogeneity. 26675134 7 7 theme heterogeneity 1110:1122 arg1 source 1100:1105 the source 1096:1105 the source of heterogeneity 1096:1122 Incubation with N-glycosidase F normalised all isoform masses to that of the quiescent naked protein, confirming the N-linked oligosaccharide as the source of heterogeneity. 26675134 8 8 dep showed 1154:1159 arg1 absence 1195:1201 the absence 1191:1201 the absence of the penultimate Gal from the biantennary oligosaccharides 1191:1262 β1,4 galactosidase treatment showed the structural difference was the absence of the penultimate Gal from the biantennary oligosaccharides, and mapping of tryptic glycopeptides confirmed these results showing that approximately half the chains lacked Gal. 26675134 10 9 theme fibrin 1598:1603 arg1 monomers 1605:1612 fibrin monomers 1598:1612 fibrin monomers 1598:1612 This has two desirable haemostatic outcomes: fibrin monomers will polymerise and form clots more rapidly, and two galactose residues can never be exposed diminishing uptake of the protein by the asialoglycoprotein receptor and ramping up concentration at a time of challenge. 26675134 0 10 from Variation 0:8 arg1 response 69:76 the acute phase response 53:76 the acute phase response 53:76 Variation of fibrinogen oligosaccharide structure in the acute phase response: Possible haemorrhagic implications. 26675134 5 11 theme N-glycosidase 698:710 arg1 F 712:712 N-glycosidase F 698:712 N-glycosidase F 698:712 Fibrinogen chains were examined directly by ESI mass spectrometry before and after digestion with N-glycosidase F and β1,4 galactosidase. 26675134 7 12 theme N-glycosidase 967:979 arg1 F 981:981 N-glycosidase F 967:981 N-glycosidase F 967:981 Incubation with N-glycosidase F normalised all isoform masses to that of the quiescent naked protein, confirming the N-linked oligosaccharide as the source of heterogeneity. 26675134 0 13 theme haemorrhagic 88:99 arg1 implications 101:112 Possible haemorrhagic implications 79:112 Possible haemorrhagic implications 79:112 Variation of fibrinogen oligosaccharide structure in the acute phase response: Possible haemorrhagic implications. 26675134 8 14 from oligosaccharides 1247:1262 arg1 absence 1195:1201 the absence 1191:1201 the absence of the penultimate Gal from the biantennary oligosaccharides 1191:1262 β1,4 galactosidase treatment showed the structural difference was the absence of the penultimate Gal from the biantennary oligosaccharides, and mapping of tryptic glycopeptides confirmed these results showing that approximately half the chains lacked Gal. 26675134 8 14 from oligosaccharides 1247:1262 arg1 Gal 1222:1224 the penultimate Gal 1206:1224 the penultimate Gal from the biantennary oligosaccharides 1206:1262 β1,4 galactosidase treatment showed the structural difference was the absence of the penultimate Gal from the biantennary oligosaccharides, and mapping of tryptic glycopeptides confirmed these results showing that approximately half the chains lacked Gal. 26675134 5 15 theme ESI 644:646 arg1 spectrometry 653:664 ESI mass spectrometry 644:664 ESI mass spectrometry 644:664 Fibrinogen chains were examined directly by ESI mass spectrometry before and after digestion with N-glycosidase F and β1,4 galactosidase. 26675134 10 16 contain has 1558:1560 arg1 This 1553:1556 This 1553:1556 This 1553:1556 This has two desirable haemostatic outcomes: fibrin monomers will polymerise and form clots more rapidly, and two galactose residues can never be exposed diminishing uptake of the protein by the asialoglycoprotein receptor and ramping up concentration at a time of challenge. 26675134 10 16 contain has 1558:1560 arg2 outcomes 1588:1595 two desirable haemostatic outcomes 1562:1595 two desirable haemostatic outcomes 1562:1595 This has two desirable haemostatic outcomes: fibrin monomers will polymerise and form clots more rapidly, and two galactose residues can never be exposed diminishing uptake of the protein by the asialoglycoprotein receptor and ramping up concentration at a time of challenge. 26675134 5 17 theme mass 648:651 arg1 spectrometry 653:664 ESI mass spectrometry 644:664 ESI mass spectrometry 644:664 Fibrinogen chains were examined directly by ESI mass spectrometry before and after digestion with N-glycosidase F and β1,4 galactosidase. 26675134 0 18 dep implications 101:112 arg1 Variation 0:8 Variation 0:8 Variation of fibrinogen oligosaccharide structure in the acute phase response 0:76 Variation of fibrinogen oligosaccharide structure in the acute phase response: Possible haemorrhagic implications. 26675134 6 19 theme Bβ 750:751 arg1 chains 759:764 The Bβ and γ chains 746:764 RESULTS The Bβ and γ chains of acute phase fibrinogen 738:790 RESULTS The Bβ and γ chains of acute phase fibrinogen showed a mass decrease of 162 Da (Gal) in some 50% of the molecules, and the Bβ chain showed an additional decrease corresponding to a further loss of NAcGlc. 26675134 8 20 theme biantennary 1235:1245 arg1 oligosaccharides 1247:1262 the biantennary oligosaccharides 1231:1262 the biantennary oligosaccharides 1231:1262 β1,4 galactosidase treatment showed the structural difference was the absence of the penultimate Gal from the biantennary oligosaccharides, and mapping of tryptic glycopeptides confirmed these results showing that approximately half the chains lacked Gal. 26675134 8 21 theme structural 1165:1174 arg1 difference 1176:1185 the structural difference 1161:1185 the structural difference 1161:1185 β1,4 galactosidase treatment showed the structural difference was the absence of the penultimate Gal from the biantennary oligosaccharides, and mapping of tryptic glycopeptides confirmed these results showing that approximately half the chains lacked Gal. 26675134 4 22 theme plasma 516:521 arg1 samples 523:529 plasma samples 516:529 plasma samples 516:529 METHODS A series of plasma samples was obtained from two individuals suffering an acute phase response. 26675134 8 23 theme penultimate 1210:1220 arg1 Gal 1222:1224 the penultimate Gal 1206:1224 the penultimate Gal from the biantennary oligosaccharides 1206:1262 β1,4 galactosidase treatment showed the structural difference was the absence of the penultimate Gal from the biantennary oligosaccharides, and mapping of tryptic glycopeptides confirmed these results showing that approximately half the chains lacked Gal. 26675134 5 24 theme Fibrinogen 600:609 arg1 chains 611:616 Fibrinogen chains 600:616 Fibrinogen chains 600:616 Fibrinogen chains were examined directly by ESI mass spectrometry before and after digestion with N-glycosidase F and β1,4 galactosidase. 26675134 10 25 theme galactose 1667:1675 arg1 residues 1677:1684 two galactose residues 1663:1684 two galactose residues 1663:1684 This has two desirable haemostatic outcomes: fibrin monomers will polymerise and form clots more rapidly, and two galactose residues can never be exposed diminishing uptake of the protein by the asialoglycoprotein receptor and ramping up concentration at a time of challenge. 26675134 3 26 theme acute 472:476 arg1 fibrinogen 484:493 quiescent and acute phase fibrinogen 458:493 quiescent and acute phase fibrinogen 458:493 To explore this, we examined the differences between the oligosaccharide structures of quiescent and acute phase fibrinogen. 26675134 9 27 dep CONCLUSIONS 1381:1391 arg1 failure 1414:1420 The failure 1410:1420 CONCLUSIONS AND IMPLICATIONS The failure of incorporation Gal 1381:1441 CONCLUSIONS AND IMPLICATIONS The failure of incorporation Gal excludes the possibility of the hepatic NAcNeu Gal transferase capping the oligosaccharides with sialic acid. 26675134 9 28 with oligosaccharides 1518:1533 arg1 acid 1547:1550 sialic acid 1540:1550 sialic acid 1540:1550 CONCLUSIONS AND IMPLICATIONS The failure of incorporation Gal excludes the possibility of the hepatic NAcNeu Gal transferase capping the oligosaccharides with sialic acid. 26675134 6 29 dep RESULTS 738:744 arg1 chains 759:764 The Bβ and γ chains 746:764 RESULTS The Bβ and γ chains of acute phase fibrinogen 738:790 RESULTS The Bβ and γ chains of acute phase fibrinogen showed a mass decrease of 162 Da (Gal) in some 50% of the molecules, and the Bβ chain showed an additional decrease corresponding to a further loss of NAcGlc. 26675134 10 30 theme challenge 1818:1826 arg1 time 1810:1813 a time 1808:1813 a time of challenge 1808:1826 This has two desirable haemostatic outcomes: fibrin monomers will polymerise and form clots more rapidly, and two galactose residues can never be exposed diminishing uptake of the protein by the asialoglycoprotein receptor and ramping up concentration at a time of challenge. 26675134 7 31 theme quiescent 1028:1036 arg1 protein 1044:1050 the quiescent naked protein 1024:1050 the quiescent naked protein 1024:1050 Incubation with N-glycosidase F normalised all isoform masses to that of the quiescent naked protein, confirming the N-linked oligosaccharide as the source of heterogeneity. 26675134 9 32 theme hepatic 1475:1481 arg1 transferase 1494:1504 the hepatic NAcNeu Gal transferase 1471:1504 the hepatic NAcNeu Gal transferase capping the oligosaccharides with sialic acid 1471:1550 CONCLUSIONS AND IMPLICATIONS The failure of incorporation Gal excludes the possibility of the hepatic NAcNeu Gal transferase capping the oligosaccharides with sialic acid. 26675134 4 33 theme phase 584:588 arg1 response 590:597 an acute phase response 575:597 an acute phase response 575:597 METHODS A series of plasma samples was obtained from two individuals suffering an acute phase response. 26675134 7 34 theme N-linked 1068:1075 arg1 oligosaccharide 1077:1091 the N-linked oligosaccharide 1064:1091 the N-linked oligosaccharide 1064:1091 Incubation with N-glycosidase F normalised all isoform masses to that of the quiescent naked protein, confirming the N-linked oligosaccharide as the source of heterogeneity. 26675134 7 34 theme N-linked 1068:1075 arg1 source 1100:1105 the source 1096:1105 the source of heterogeneity 1096:1122 Incubation with N-glycosidase F normalised all isoform masses to that of the quiescent naked protein, confirming the N-linked oligosaccharide as the source of heterogeneity. 26675134 3 35 theme quiescent 458:466 arg1 fibrinogen 484:493 quiescent and acute phase fibrinogen 458:493 quiescent and acute phase fibrinogen 458:493 To explore this, we examined the differences between the oligosaccharide structures of quiescent and acute phase fibrinogen. 26675134 0 36 theme oligosaccharide 24:38 arg1 structure 40:48 fibrinogen oligosaccharide structure 13:48 fibrinogen oligosaccharide structure 13:48 Variation of fibrinogen oligosaccharide structure in the acute phase response: Possible haemorrhagic implications. 26675134 4 37 theme acute 578:582 arg1 response 590:597 an acute phase response 575:597 an acute phase response 575:597 METHODS A series of plasma samples was obtained from two individuals suffering an acute phase response. 26675134 6 38 theme mass 801:804 arg1 decrease 806:813 a mass decrease 799:813 a mass decrease of 162 Da (Gal) 799:829 RESULTS The Bβ and γ chains of acute phase fibrinogen showed a mass decrease of 162 Da (Gal) in some 50% of the molecules, and the Bβ chain showed an additional decrease corresponding to a further loss of NAcGlc. 26675134 9 39 theme Gal 1490:1492 arg1 transferase 1494:1504 the hepatic NAcNeu Gal transferase 1471:1504 the hepatic NAcNeu Gal transferase capping the oligosaccharides with sialic acid 1471:1550 CONCLUSIONS AND IMPLICATIONS The failure of incorporation Gal excludes the possibility of the hepatic NAcNeu Gal transferase capping the oligosaccharides with sialic acid. 26675134 0 40 theme fibrinogen 13:22 arg1 structure 40:48 fibrinogen oligosaccharide structure 13:48 fibrinogen oligosaccharide structure 13:48 Variation of fibrinogen oligosaccharide structure in the acute phase response: Possible haemorrhagic implications. 26675134 6 41 theme NAcGlc 943:948 arg1 loss 935:938 a further loss 925:938 a further loss of NAcGlc 925:948 RESULTS The Bβ and γ chains of acute phase fibrinogen showed a mass decrease of 162 Da (Gal) in some 50% of the molecules, and the Bβ chain showed an additional decrease corresponding to a further loss of NAcGlc. 26675134 1 42 theme BACKGROUND 115:124 arg1 glycoprotein 155:166 an acute phase glycoprotein 140:166 an acute phase glycoprotein whose concentration increases in response to trauma 140:218 BACKGROUND Fibrinogen is an acute phase glycoprotein whose concentration increases in response to trauma. 26675134 1 42 theme BACKGROUND 115:124 arg1 Fibrinogen 126:135 BACKGROUND Fibrinogen 115:135 BACKGROUND Fibrinogen 115:135 BACKGROUND Fibrinogen is an acute phase glycoprotein whose concentration increases in response to trauma. 26675134 8 43 from absence 1195:1201 arg1 oligosaccharides 1247:1262 the biantennary oligosaccharides 1231:1262 the biantennary oligosaccharides 1231:1262 β1,4 galactosidase treatment showed the structural difference was the absence of the penultimate Gal from the biantennary oligosaccharides, and mapping of tryptic glycopeptides confirmed these results showing that approximately half the chains lacked Gal. 26675134 9 44 theme transferase 1494:1504 arg1 possibility 1456:1466 the possibility 1452:1466 the possibility of the hepatic NAcNeu Gal transferase capping the oligosaccharides with sialic acid 1452:1550 CONCLUSIONS AND IMPLICATIONS The failure of incorporation Gal excludes the possibility of the hepatic NAcNeu Gal transferase capping the oligosaccharides with sialic acid. 26675134 3 45 theme oligosaccharide 428:442 arg1 structures 444:453 the oligosaccharide structures 424:453 the oligosaccharide structures of quiescent and acute phase fibrinogen 424:493 To explore this, we examined the differences between the oligosaccharide structures of quiescent and acute phase fibrinogen. 26675134 8 46 theme glycopeptides 1288:1300 arg1 mapping 1269:1275 mapping 1269:1275 mapping of tryptic glycopeptides 1269:1300 β1,4 galactosidase treatment showed the structural difference was the absence of the penultimate Gal from the biantennary oligosaccharides, and mapping of tryptic glycopeptides confirmed these results showing that approximately half the chains lacked Gal. 26675134 7 47 theme naked 1038:1042 arg1 protein 1044:1050 the quiescent naked protein 1024:1050 the quiescent naked protein 1024:1050 Incubation with N-glycosidase F normalised all isoform masses to that of the quiescent naked protein, confirming the N-linked oligosaccharide as the source of heterogeneity. 26675134 8 48 theme tryptic 1280:1286 arg1 glycopeptides 1288:1300 tryptic glycopeptides 1280:1300 tryptic glycopeptides 1280:1300 β1,4 galactosidase treatment showed the structural difference was the absence of the penultimate Gal from the biantennary oligosaccharides, and mapping of tryptic glycopeptides confirmed these results showing that approximately half the chains lacked Gal. 26675134 8 49 dep half 1353:1356 arg1 chains 1362:1367 the chains 1358:1367 approximately half the chains 1339:1367 β1,4 galactosidase treatment showed the structural difference was the absence of the penultimate Gal from the biantennary oligosaccharides, and mapping of tryptic glycopeptides confirmed these results showing that approximately half the chains lacked Gal. 26675134 9 50 theme NAcNeu 1483:1488 arg1 transferase 1494:1504 the hepatic NAcNeu Gal transferase 1471:1504 the hepatic NAcNeu Gal transferase capping the oligosaccharides with sialic acid 1471:1550 CONCLUSIONS AND IMPLICATIONS The failure of incorporation Gal excludes the possibility of the hepatic NAcNeu Gal transferase capping the oligosaccharides with sialic acid. 26675134 3 51 theme phase 478:482 arg1 fibrinogen 484:493 quiescent and acute phase fibrinogen 458:493 quiescent and acute phase fibrinogen 458:493 To explore this, we examined the differences between the oligosaccharide structures of quiescent and acute phase fibrinogen. 26675134 0 52 theme structure 40:48 arg1 Variation 0:8 Variation 0:8 Variation of fibrinogen oligosaccharide structure in the acute phase response 0:76 Variation of fibrinogen oligosaccharide structure in the acute phase response: Possible haemorrhagic implications. 26675134 6 53 theme molecules 850:858 arg1 % 841:841 some 50% 834:841 some 50% of the molecules 834:858 RESULTS The Bβ and γ chains of acute phase fibrinogen showed a mass decrease of 162 Da (Gal) in some 50% of the molecules, and the Bβ chain showed an additional decrease corresponding to a further loss of NAcGlc. 26675134 6 53 theme molecules 850:858 arg1 molecules 850:858 the molecules 846:858 the molecules 846:858 RESULTS The Bβ and γ chains of acute phase fibrinogen showed a mass decrease of 162 Da (Gal) in some 50% of the molecules, and the Bβ chain showed an additional decrease corresponding to a further loss of NAcGlc. 26675134 9 54 theme Gal 1439:1441 arg1 failure 1414:1420 The failure 1410:1420 CONCLUSIONS AND IMPLICATIONS The failure of incorporation Gal 1381:1441 CONCLUSIONS AND IMPLICATIONS The failure of incorporation Gal excludes the possibility of the hepatic NAcNeu Gal transferase capping the oligosaccharides with sialic acid. 26675134 3 55 theme fibrinogen 484:493 arg1 structures 444:453 the oligosaccharide structures 424:453 the oligosaccharide structures of quiescent and acute phase fibrinogen 424:493 To explore this, we examined the differences between the oligosaccharide structures of quiescent and acute phase fibrinogen. 26675134 0 56 theme acute 57:61 arg1 response 69:76 the acute phase response 53:76 the acute phase response 53:76 Variation of fibrinogen oligosaccharide structure in the acute phase response: Possible haemorrhagic implications. 26675134 6 57 theme further 927:933 arg1 loss 935:938 a further loss 925:938 a further loss of NAcGlc 925:948 RESULTS The Bβ and γ chains of acute phase fibrinogen showed a mass decrease of 162 Da (Gal) in some 50% of the molecules, and the Bβ chain showed an additional decrease corresponding to a further loss of NAcGlc. 26675134 1 58 gly glycoprotein 155:166 arg1 glycoprotein 155:166 an acute phase glycoprotein 140:166 an acute phase glycoprotein whose concentration increases in response to trauma 140:218 BACKGROUND Fibrinogen is an acute phase glycoprotein whose concentration increases in response to trauma. 26675134 1 58 gly glycoprotein 155:166 arg1 Fibrinogen 126:135 BACKGROUND Fibrinogen 115:135 BACKGROUND Fibrinogen 115:135 BACKGROUND Fibrinogen is an acute phase glycoprotein whose concentration increases in response to trauma. 26675134 6 59 theme Bβ 869:870 arg1 chain 872:876 the Bβ chain 865:876 the Bβ chain 865:876 RESULTS The Bβ and γ chains of acute phase fibrinogen showed a mass decrease of 162 Da (Gal) in some 50% of the molecules, and the Bβ chain showed an additional decrease corresponding to a further loss of NAcGlc. 26675134 8 60 theme Gal 1222:1224 arg1 absence 1195:1201 the absence 1191:1201 the absence of the penultimate Gal from the biantennary oligosaccharides 1191:1262 β1,4 galactosidase treatment showed the structural difference was the absence of the penultimate Gal from the biantennary oligosaccharides, and mapping of tryptic glycopeptides confirmed these results showing that approximately half the chains lacked Gal. 26675134 5 61 theme β1,4 718:721 arg1 galactosidase 723:735 β1,4 galactosidase 718:735 β1,4 galactosidase 718:735 Fibrinogen chains were examined directly by ESI mass spectrometry before and after digestion with N-glycosidase F and β1,4 galactosidase. 26675134 10 62 theme haemostatic 1576:1586 arg1 outcomes 1588:1595 two desirable haemostatic outcomes 1562:1595 two desirable haemostatic outcomes 1562:1595 This has two desirable haemostatic outcomes: fibrin monomers will polymerise and form clots more rapidly, and two galactose residues can never be exposed diminishing uptake of the protein by the asialoglycoprotein receptor and ramping up concentration at a time of challenge. 26675134 2 63 theme synthesised 231:241 arg1 protein 243:249 The newly synthesised protein 221:249 The newly synthesised protein 221:249 The newly synthesised protein is functionally enhanced and it is known that treatment with neuraminidase increases the rate of fibrin polymerisation. 26675134 6 64 theme fibrinogen 781:790 arg1 chains 759:764 The Bβ and γ chains 746:764 RESULTS The Bβ and γ chains of acute phase fibrinogen 738:790 RESULTS The Bβ and γ chains of acute phase fibrinogen showed a mass decrease of 162 Da (Gal) in some 50% of the molecules, and the Bβ chain showed an additional decrease corresponding to a further loss of NAcGlc. 26675134 2 65 theme polymerisation 355:368 arg1 rate 340:343 the rate 336:343 the rate of fibrin polymerisation 336:368 The newly synthesised protein is functionally enhanced and it is known that treatment with neuraminidase increases the rate of fibrin polymerisation. 26675134 7 66 with Incubation 951:960 arg1 F 981:981 N-glycosidase F 967:981 N-glycosidase F 967:981 Incubation with N-glycosidase F normalised all isoform masses to that of the quiescent naked protein, confirming the N-linked oligosaccharide as the source of heterogeneity. 26675134 6 67 theme 162 Da 818:823 arg1 decrease 806:813 a mass decrease 799:813 a mass decrease of 162 Da (Gal) 799:829 RESULTS The Bβ and γ chains of acute phase fibrinogen showed a mass decrease of 162 Da (Gal) in some 50% of the molecules, and the Bβ chain showed an additional decrease corresponding to a further loss of NAcGlc. 26675134 6 68 theme phase 775:779 arg1 fibrinogen 781:790 acute phase fibrinogen 769:790 acute phase fibrinogen 769:790 RESULTS The Bβ and γ chains of acute phase fibrinogen showed a mass decrease of 162 Da (Gal) in some 50% of the molecules, and the Bβ chain showed an additional decrease corresponding to a further loss of NAcGlc. 26675134 2 69 theme fibrin 348:353 arg1 polymerisation 355:368 fibrin polymerisation 348:368 fibrin polymerisation 348:368 The newly synthesised protein is functionally enhanced and it is known that treatment with neuraminidase increases the rate of fibrin polymerisation. 26675134 10 70 theme asialoglycoprotein 1748:1765 arg1 receptor 1767:1774 the asialoglycoprotein receptor 1744:1774 the asialoglycoprotein receptor 1744:1774 This has two desirable haemostatic outcomes: fibrin monomers will polymerise and form clots more rapidly, and two galactose residues can never be exposed diminishing uptake of the protein by the asialoglycoprotein receptor and ramping up concentration at a time of challenge. 26675134 7 71 theme isoform 998:1004 arg1 masses 1006:1011 all isoform masses 994:1011 all isoform masses 994:1011 Incubation with N-glycosidase F normalised all isoform masses to that of the quiescent naked protein, confirming the N-linked oligosaccharide as the source of heterogeneity. 26675134 10 72 gly asialoglycoprotein 1748:1765 arg1 asialoglycoprotein 1748:1765 the asialoglycoprotein receptor 1744:1774 the asialoglycoprotein receptor 1744:1774 This has two desirable haemostatic outcomes: fibrin monomers will polymerise and form clots more rapidly, and two galactose residues can never be exposed diminishing uptake of the protein by the asialoglycoprotein receptor and ramping up concentration at a time of challenge. 26675134 6 73 theme acute 769:773 arg1 fibrinogen 781:790 acute phase fibrinogen 769:790 acute phase fibrinogen 769:790 RESULTS The Bβ and γ chains of acute phase fibrinogen showed a mass decrease of 162 Da (Gal) in some 50% of the molecules, and the Bβ chain showed an additional decrease corresponding to a further loss of NAcGlc. 26675134 1 74 theme acute 143:147 arg1 glycoprotein 155:166 an acute phase glycoprotein 140:166 an acute phase glycoprotein whose concentration increases in response to trauma 140:218 BACKGROUND Fibrinogen is an acute phase glycoprotein whose concentration increases in response to trauma. 26675134 1 74 theme acute 143:147 arg1 Fibrinogen 126:135 BACKGROUND Fibrinogen 115:135 BACKGROUND Fibrinogen 115:135 BACKGROUND Fibrinogen is an acute phase glycoprotein whose concentration increases in response to trauma. 26675134 9 75 theme sialic 1540:1545 arg1 acid 1547:1550 sialic acid 1540:1550 sialic acid 1540:1550 CONCLUSIONS AND IMPLICATIONS The failure of incorporation Gal excludes the possibility of the hepatic NAcNeu Gal transferase capping the oligosaccharides with sialic acid. 26675134 8 76 theme β1,4 1125:1128 arg1 treatment 1144:1152 β1,4 galactosidase treatment 1125:1152 β1,4 galactosidase treatment 1125:1152 β1,4 galactosidase treatment showed the structural difference was the absence of the penultimate Gal from the biantennary oligosaccharides, and mapping of tryptic glycopeptides confirmed these results showing that approximately half the chains lacked Gal. 26675134 10 77 theme protein 1733:1739 arg1 uptake 1719:1724 uptake 1719:1724 uptake of the protein by the asialoglycoprotein receptor 1719:1774 This has two desirable haemostatic outcomes: fibrin monomers will polymerise and form clots more rapidly, and two galactose residues can never be exposed diminishing uptake of the protein by the asialoglycoprotein receptor and ramping up concentration at a time of challenge. 26675134 1 78 theme phase 149:153 arg1 glycoprotein 155:166 an acute phase glycoprotein 140:166 an acute phase glycoprotein whose concentration increases in response to trauma 140:218 BACKGROUND Fibrinogen is an acute phase glycoprotein whose concentration increases in response to trauma. 26675134 1 78 theme phase 149:153 arg1 Fibrinogen 126:135 BACKGROUND Fibrinogen 115:135 BACKGROUND Fibrinogen 115:135 BACKGROUND Fibrinogen is an acute phase glycoprotein whose concentration increases in response to trauma. 26675134 7 79 link N-linked 1068:1075 arg1 oligosaccharide 1077:1091 the N-linked oligosaccharide 1064:1091 the N-linked oligosaccharide 1064:1091 Incubation with N-glycosidase F normalised all isoform masses to that of the quiescent naked protein, confirming the N-linked oligosaccharide as the source of heterogeneity. 26675134 7 79 link N-linked 1068:1075 arg1 source 1100:1105 the source 1096:1105 the source of heterogeneity 1096:1122 Incubation with N-glycosidase F normalised all isoform masses to that of the quiescent naked protein, confirming the N-linked oligosaccharide as the source of heterogeneity. 26675134 10 80 theme desirable 1566:1574 arg1 outcomes 1588:1595 two desirable haemostatic outcomes 1562:1595 two desirable haemostatic outcomes 1562:1595 This has two desirable haemostatic outcomes: fibrin monomers will polymerise and form clots more rapidly, and two galactose residues can never be exposed diminishing uptake of the protein by the asialoglycoprotein receptor and ramping up concentration at a time of challenge. 26675134 0 81 theme phase 63:67 arg1 response 69:76 the acute phase response 53:76 the acute phase response 53:76 Variation of fibrinogen oligosaccharide structure in the acute phase response: Possible haemorrhagic implications. 26675134 8 82 gly glycopeptides 1288:1300 arg2 glycopeptides 1288:1300 tryptic glycopeptides 1280:1300 tryptic glycopeptides 1280:1300 β1,4 galactosidase treatment showed the structural difference was the absence of the penultimate Gal from the biantennary oligosaccharides, and mapping of tryptic glycopeptides confirmed these results showing that approximately half the chains lacked Gal. 26675134 9 83 theme incorporation 1425:1437 arg1 Gal 1439:1441 incorporation Gal 1425:1441 incorporation Gal 1425:1441 CONCLUSIONS AND IMPLICATIONS The failure of incorporation Gal excludes the possibility of the hepatic NAcNeu Gal transferase capping the oligosaccharides with sialic acid. 26675134 2 84 with treatment 297:305 arg1 neuraminidase 312:324 neuraminidase 312:324 neuraminidase 312:324 The newly synthesised protein is functionally enhanced and it is known that treatment with neuraminidase increases the rate of fibrin polymerisation. 24992528 2 0 theme binding 577:583 arg1 capable 566:572 capable 566:572 capable 566:572 If the target region is a supersite of HIV-1 vulnerability, recognized by a collection of broadly neutralizing antibodies, this strategy affords the creation of "supersite transplants", capable of binding (and potentially eliciting) antibodies similar to the template collection of effective antibodies. 24992528 1 1 from region 294:299 arg1 scaffold 327:334 a heterologous protein scaffold 304:334 a heterologous protein scaffold with preserved antibody-binding properties 304:377 One strategy for isolating or eliciting antibodies against a specific target region on the envelope glycoprotein trimer (Env) of the human immunodeficiency virus type 1 (HIV-1) involves the creation of site transplants, which present the target region on a heterologous protein scaffold with preserved antibody-binding properties. 24992528 2 2 theme capable 566:572 arg1 antibodies 613:622 capable of binding (and potentially eliciting) antibodies 566:622 capable of binding (and potentially eliciting) antibodies 566:622 If the target region is a supersite of HIV-1 vulnerability, recognized by a collection of broadly neutralizing antibodies, this strategy affords the creation of "supersite transplants", capable of binding (and potentially eliciting) antibodies similar to the template collection of effective antibodies. 24992528 4 3 theme antibody 1034:1041 arg1 PG9 1043:1045 antibody PG9 1034:1045 antibody PG9 1034:1045 To implement our strategy, we chose a single representative antibody against each of the target supersites: antibody 10E8, which recognizes the membrane-proximal external region (MPER) on the HIV-1 gp41 glycoprotein; antibody PG9, which recognizes variable regions one and two (V1V2) on the HIV-1 gp120 glycoprotein; and antibody PGT128 which recognizes a glycopeptide supersite in variable region 3 (glycan V3) on gp120. 24992528 9 4 theme Env 2127:2129 arg1 rest 2113:2116 the rest 2109:2116 the rest of HIV-1 Env 2109:2129 Essential elements of the glycan V3 supersite, embodied by as few as 3 N-linked glycans and ∼ 25 Env residues, can be segregated into acceptor scaffolds away from the immune-evading capabilities of the rest of HIV-1 Env, thereby providing a means to focus the immune response on the scaffolded supersite. 24992528 5 5 theme 100-supersite 1380:1392 arg1 transplants 1394:1404 100-supersite transplants 1380:1404 100-supersite transplants in a 96-well microtiter-plate format 1380:1441 We used a structural alignment algorithm to identify suitable acceptor proteins, and then designed, expressed, and tested antigenically over 100-supersite transplants in a 96-well microtiter-plate format. 24992528 4 6 gly glycopeptide 1173:1184 arg2 glycopeptide 1173:1184 glycopeptide 1173:1184 glycopeptide 1173:1184 To implement our strategy, we chose a single representative antibody against each of the target supersites: antibody 10E8, which recognizes the membrane-proximal external region (MPER) on the HIV-1 gp41 glycoprotein; antibody PG9, which recognizes variable regions one and two (V1V2) on the HIV-1 gp120 glycoprotein; and antibody PGT128 which recognizes a glycopeptide supersite in variable region 3 (glycan V3) on gp120. 24992528 2 7 theme eliciting 602:610 arg1 antibodies 613:622 capable of binding (and potentially eliciting) antibodies 566:622 capable of binding (and potentially eliciting) antibodies 566:622 If the target region is a supersite of HIV-1 vulnerability, recognized by a collection of broadly neutralizing antibodies, this strategy affords the creation of "supersite transplants", capable of binding (and potentially eliciting) antibodies similar to the template collection of effective antibodies. 24992528 7 8 theme supersite 1792:1800 arg1 requirement 1764:1774 the mannose9-N-linked glycan requirement 1735:1774 the mannose9-N-linked glycan requirement of the template supersite 1735:1800 However, seven of the glycan V3-supersite transplants exhibited nanomolar affinity to effective neutralizing antibodies from at least three donors and recapitulated the mannose9-N-linked glycan requirement of the template supersite. 24992528 9 9 theme V3 1944:1945 arg1 supersite 1947:1955 the glycan V3 supersite 1933:1955 the glycan V3 supersite 1933:1955 Essential elements of the glycan V3 supersite, embodied by as few as 3 N-linked glycans and ∼ 25 Env residues, can be segregated into acceptor scaffolds away from the immune-evading capabilities of the rest of HIV-1 Env, thereby providing a means to focus the immune response on the scaffolded supersite. 24992528 3 10 theme vulnerability 729:741 arg1 vulnerability 729:741 HIV-1 vulnerability 723:741 HIV-1 vulnerability 723:741 Here we transplant three supersites of HIV-1 vulnerability, each targeted by effective neutralizing antibodies from multiple donors. 24992528 3 10 theme vulnerability 729:741 arg1 each 744:747 each 744:747 each 744:747 Here we transplant three supersites of HIV-1 vulnerability, each targeted by effective neutralizing antibodies from multiple donors. 24992528 3 10 theme vulnerability 729:741 arg1 supersites 709:718 three supersites 703:718 three supersites of HIV-1 vulnerability 703:741 Here we transplant three supersites of HIV-1 vulnerability, each targeted by effective neutralizing antibodies from multiple donors. 24992528 6 11 theme transplants 1474:1484 arg1 majority 1448:1455 The majority 1444:1455 The majority of the supersite transplants 1444:1484 The majority of the supersite transplants failed to maintain the antigenic properties of their respective template supersite. 24992528 7 12 theme transplants 1612:1622 arg1 seven 1579:1583 seven 1579:1583 seven 1579:1583 However, seven of the glycan V3-supersite transplants exhibited nanomolar affinity to effective neutralizing antibodies from at least three donors and recapitulated the mannose9-N-linked glycan requirement of the template supersite. 24992528 7 12 theme transplants 1612:1622 arg1 transplants 1612:1622 the glycan V3-supersite transplants 1588:1622 the glycan V3-supersite transplants 1588:1622 However, seven of the glycan V3-supersite transplants exhibited nanomolar affinity to effective neutralizing antibodies from at least three donors and recapitulated the mannose9-N-linked glycan requirement of the template supersite. 24992528 4 13 theme target 906:911 arg1 supersites 913:922 the target supersites 902:922 the target supersites 902:922 To implement our strategy, we chose a single representative antibody against each of the target supersites: antibody 10E8, which recognizes the membrane-proximal external region (MPER) on the HIV-1 gp41 glycoprotein; antibody PG9, which recognizes variable regions one and two (V1V2) on the HIV-1 gp120 glycoprotein; and antibody PGT128 which recognizes a glycopeptide supersite in variable region 3 (glycan V3) on gp120. 24992528 1 14 theme immunodeficiency 188:203 arg1 HIV-1 219:223 HIV-1 219:223 HIV-1 219:223 One strategy for isolating or eliciting antibodies against a specific target region on the envelope glycoprotein trimer (Env) of the human immunodeficiency virus type 1 (HIV-1) involves the creation of site transplants, which present the target region on a heterologous protein scaffold with preserved antibody-binding properties. 24992528 1 14 theme immunodeficiency 188:203 arg1 type 211:214 the human immunodeficiency virus type 1 178:216 the human immunodeficiency virus type 1 (HIV-1) 178:224 One strategy for isolating or eliciting antibodies against a specific target region on the envelope glycoprotein trimer (Env) of the human immunodeficiency virus type 1 (HIV-1) involves the creation of site transplants, which present the target region on a heterologous protein scaffold with preserved antibody-binding properties. 24992528 7 15 theme glycan 1592:1597 arg1 transplants 1612:1622 the glycan V3-supersite transplants 1588:1622 the glycan V3-supersite transplants 1588:1622 However, seven of the glycan V3-supersite transplants exhibited nanomolar affinity to effective neutralizing antibodies from at least three donors and recapitulated the mannose9-N-linked glycan requirement of the template supersite. 24992528 1 16 theme type 211:214 arg1 Env 170:172 Env 170:172 Env 170:172 One strategy for isolating or eliciting antibodies against a specific target region on the envelope glycoprotein trimer (Env) of the human immunodeficiency virus type 1 (HIV-1) involves the creation of site transplants, which present the target region on a heterologous protein scaffold with preserved antibody-binding properties. 24992528 1 16 theme type 211:214 arg1 trimer 162:167 the envelope glycoprotein trimer 136:167 the envelope glycoprotein trimer (Env) of the human immunodeficiency virus type 1 (HIV-1) 136:224 One strategy for isolating or eliciting antibodies against a specific target region on the envelope glycoprotein trimer (Env) of the human immunodeficiency virus type 1 (HIV-1) involves the creation of site transplants, which present the target region on a heterologous protein scaffold with preserved antibody-binding properties. 24992528 2 17 theme " 563:563 arg1 creation 529:536 the creation 525:536 the creation of "supersite transplants" 525:563 If the target region is a supersite of HIV-1 vulnerability, recognized by a collection of broadly neutralizing antibodies, this strategy affords the creation of "supersite transplants", capable of binding (and potentially eliciting) antibodies similar to the template collection of effective antibodies. 24992528 4 18 gly glycoprotein 1020:1031 arg1 glycoprotein 1020:1031 the HIV-1 gp41 glycoprotein 1005:1031 the HIV-1 gp41 glycoprotein 1005:1031 To implement our strategy, we chose a single representative antibody against each of the target supersites: antibody 10E8, which recognizes the membrane-proximal external region (MPER) on the HIV-1 gp41 glycoprotein; antibody PG9, which recognizes variable regions one and two (V1V2) on the HIV-1 gp120 glycoprotein; and antibody PGT128 which recognizes a glycopeptide supersite in variable region 3 (glycan V3) on gp120. 24992528 6 19 theme template 1550:1557 arg1 supersite 1559:1567 their respective template supersite 1533:1567 their respective template supersite 1533:1567 The majority of the supersite transplants failed to maintain the antigenic properties of their respective template supersite. 24992528 4 20 theme representative 862:875 arg1 antibody 877:884 a single representative antibody 853:884 a single representative antibody against each of the target supersites 853:922 To implement our strategy, we chose a single representative antibody against each of the target supersites: antibody 10E8, which recognizes the membrane-proximal external region (MPER) on the HIV-1 gp41 glycoprotein; antibody PG9, which recognizes variable regions one and two (V1V2) on the HIV-1 gp120 glycoprotein; and antibody PGT128 which recognizes a glycopeptide supersite in variable region 3 (glycan V3) on gp120. 24992528 2 21 theme supersite 542:550 arg1 transplants 552:562 supersite transplants 542:562 "supersite transplants" 541:563 If the target region is a supersite of HIV-1 vulnerability, recognized by a collection of broadly neutralizing antibodies, this strategy affords the creation of "supersite transplants", capable of binding (and potentially eliciting) antibodies similar to the template collection of effective antibodies. 24992528 2 22 theme effective 662:670 arg1 antibodies 672:681 effective antibodies 662:681 effective antibodies 662:681 If the target region is a supersite of HIV-1 vulnerability, recognized by a collection of broadly neutralizing antibodies, this strategy affords the creation of "supersite transplants", capable of binding (and potentially eliciting) antibodies similar to the template collection of effective antibodies. 24992528 1 23 with scaffold 327:334 arg1 properties 368:377 preserved antibody-binding properties 341:377 preserved antibody-binding properties 341:377 One strategy for isolating or eliciting antibodies against a specific target region on the envelope glycoprotein trimer (Env) of the human immunodeficiency virus type 1 (HIV-1) involves the creation of site transplants, which present the target region on a heterologous protein scaffold with preserved antibody-binding properties. 24992528 2 24 theme neutralizing 478:489 arg1 antibodies 491:500 broadly neutralizing antibodies 470:500 broadly neutralizing antibodies 470:500 If the target region is a supersite of HIV-1 vulnerability, recognized by a collection of broadly neutralizing antibodies, this strategy affords the creation of "supersite transplants", capable of binding (and potentially eliciting) antibodies similar to the template collection of effective antibodies. 24992528 3 25 theme neutralizing 771:782 arg1 antibodies 784:793 effective neutralizing antibodies 761:793 effective neutralizing antibodies from multiple donors 761:814 Here we transplant three supersites of HIV-1 vulnerability, each targeted by effective neutralizing antibodies from multiple donors. 24992528 1 26 theme glycoprotein 149:160 arg1 Env 170:172 Env 170:172 Env 170:172 One strategy for isolating or eliciting antibodies against a specific target region on the envelope glycoprotein trimer (Env) of the human immunodeficiency virus type 1 (HIV-1) involves the creation of site transplants, which present the target region on a heterologous protein scaffold with preserved antibody-binding properties. 24992528 1 26 theme glycoprotein 149:160 arg1 trimer 162:167 the envelope glycoprotein trimer 136:167 the envelope glycoprotein trimer (Env) of the human immunodeficiency virus type 1 (HIV-1) 136:224 One strategy for isolating or eliciting antibodies against a specific target region on the envelope glycoprotein trimer (Env) of the human immunodeficiency virus type 1 (HIV-1) involves the creation of site transplants, which present the target region on a heterologous protein scaffold with preserved antibody-binding properties. 24992528 4 27 theme external 979:986 arg1 MPER 996:999 MPER 996:999 MPER 996:999 To implement our strategy, we chose a single representative antibody against each of the target supersites: antibody 10E8, which recognizes the membrane-proximal external region (MPER) on the HIV-1 gp41 glycoprotein; antibody PG9, which recognizes variable regions one and two (V1V2) on the HIV-1 gp120 glycoprotein; and antibody PGT128 which recognizes a glycopeptide supersite in variable region 3 (glycan V3) on gp120. 24992528 4 27 theme external 979:986 arg1 region 988:993 the membrane-proximal external region 957:993 the membrane-proximal external region (MPER) on the HIV-1 gp41 glycoprotein 957:1031 To implement our strategy, we chose a single representative antibody against each of the target supersites: antibody 10E8, which recognizes the membrane-proximal external region (MPER) on the HIV-1 gp41 glycoprotein; antibody PG9, which recognizes variable regions one and two (V1V2) on the HIV-1 gp120 glycoprotein; and antibody PGT128 which recognizes a glycopeptide supersite in variable region 3 (glycan V3) on gp120. 24992528 4 28 theme gp120 1114:1118 arg1 glycoprotein 1120:1131 the HIV-1 gp120 glycoprotein 1104:1131 the HIV-1 gp120 glycoprotein 1104:1131 To implement our strategy, we chose a single representative antibody against each of the target supersites: antibody 10E8, which recognizes the membrane-proximal external region (MPER) on the HIV-1 gp41 glycoprotein; antibody PG9, which recognizes variable regions one and two (V1V2) on the HIV-1 gp120 glycoprotein; and antibody PGT128 which recognizes a glycopeptide supersite in variable region 3 (glycan V3) on gp120. 24992528 1 29 theme heterologous 306:317 arg1 scaffold 327:334 a heterologous protein scaffold 304:334 a heterologous protein scaffold with preserved antibody-binding properties 304:377 One strategy for isolating or eliciting antibodies against a specific target region on the envelope glycoprotein trimer (Env) of the human immunodeficiency virus type 1 (HIV-1) involves the creation of site transplants, which present the target region on a heterologous protein scaffold with preserved antibody-binding properties. 24992528 9 30 theme Env 2008:2010 arg1 residues 2012:2019 ∼ 25 Env residues 2003:2019 ∼ 25 Env residues 2003:2019 Essential elements of the glycan V3 supersite, embodied by as few as 3 N-linked glycans and ∼ 25 Env residues, can be segregated into acceptor scaffolds away from the immune-evading capabilities of the rest of HIV-1 Env, thereby providing a means to focus the immune response on the scaffolded supersite. 24992528 9 31 theme N-linked 1982:1989 arg1 glycans 1991:1997 as few as 3 N-linked glycans 1970:1997 as few as 3 N-linked glycans 1970:1997 Essential elements of the glycan V3 supersite, embodied by as few as 3 N-linked glycans and ∼ 25 Env residues, can be segregated into acceptor scaffolds away from the immune-evading capabilities of the rest of HIV-1 Env, thereby providing a means to focus the immune response on the scaffolded supersite. 24992528 8 32 theme transplants 1824:1834 arg1 binding 1807:1813 The binding 1803:1813 The binding of these transplants 1803:1834 The binding of these transplants could be further enhanced by placement into self-assembling nanoparticles. 24992528 4 33 theme variable 1199:1206 arg1 V3 1225:1226 glycan V3 1218:1226 glycan V3 1218:1226 To implement our strategy, we chose a single representative antibody against each of the target supersites: antibody 10E8, which recognizes the membrane-proximal external region (MPER) on the HIV-1 gp41 glycoprotein; antibody PG9, which recognizes variable regions one and two (V1V2) on the HIV-1 gp120 glycoprotein; and antibody PGT128 which recognizes a glycopeptide supersite in variable region 3 (glycan V3) on gp120. 24992528 4 33 theme variable 1199:1206 arg1 region 1208:1213 variable region 3 1199:1215 variable region 3 (glycan V3) on gp120 1199:1236 To implement our strategy, we chose a single representative antibody against each of the target supersites: antibody 10E8, which recognizes the membrane-proximal external region (MPER) on the HIV-1 gp41 glycoprotein; antibody PG9, which recognizes variable regions one and two (V1V2) on the HIV-1 gp120 glycoprotein; and antibody PGT128 which recognizes a glycopeptide supersite in variable region 3 (glycan V3) on gp120. 24992528 1 34 theme preserved 341:349 arg1 properties 368:377 preserved antibody-binding properties 341:377 preserved antibody-binding properties 341:377 One strategy for isolating or eliciting antibodies against a specific target region on the envelope glycoprotein trimer (Env) of the human immunodeficiency virus type 1 (HIV-1) involves the creation of site transplants, which present the target region on a heterologous protein scaffold with preserved antibody-binding properties. 24992528 9 35 theme scaffolded 2194:2203 arg1 supersite 2205:2213 the scaffolded supersite 2190:2213 the scaffolded supersite 2190:2213 Essential elements of the glycan V3 supersite, embodied by as few as 3 N-linked glycans and ∼ 25 Env residues, can be segregated into acceptor scaffolds away from the immune-evading capabilities of the rest of HIV-1 Env, thereby providing a means to focus the immune response on the scaffolded supersite. 24992528 7 36 theme effective 1656:1664 arg1 antibodies 1679:1688 effective neutralizing antibodies 1656:1688 effective neutralizing antibodies from at least three donors 1656:1715 However, seven of the glycan V3-supersite transplants exhibited nanomolar affinity to effective neutralizing antibodies from at least three donors and recapitulated the mannose9-N-linked glycan requirement of the template supersite. 24992528 2 37 theme vulnerability 425:437 arg1 region 394:399 the target region 383:399 the target region 383:399 If the target region is a supersite of HIV-1 vulnerability, recognized by a collection of broadly neutralizing antibodies, this strategy affords the creation of "supersite transplants", capable of binding (and potentially eliciting) antibodies similar to the template collection of effective antibodies. 24992528 2 37 theme vulnerability 425:437 arg1 supersite 406:414 a supersite 404:414 a supersite 404:414 If the target region is a supersite of HIV-1 vulnerability, recognized by a collection of broadly neutralizing antibodies, this strategy affords the creation of "supersite transplants", capable of binding (and potentially eliciting) antibodies similar to the template collection of effective antibodies. 24992528 2 37 theme vulnerability 425:437 arg1 vulnerability 425:437 HIV-1 vulnerability 419:437 HIV-1 vulnerability 419:437 If the target region is a supersite of HIV-1 vulnerability, recognized by a collection of broadly neutralizing antibodies, this strategy affords the creation of "supersite transplants", capable of binding (and potentially eliciting) antibodies similar to the template collection of effective antibodies. 24992528 5 38 theme 96-well 1411:1417 arg1 format 1436:1441 a 96-well microtiter-plate format 1409:1441 a 96-well microtiter-plate format 1409:1441 We used a structural alignment algorithm to identify suitable acceptor proteins, and then designed, expressed, and tested antigenically over 100-supersite transplants in a 96-well microtiter-plate format. 24992528 1 39 theme site 251:254 arg1 transplants 256:266 site transplants 251:266 site transplants 251:266 One strategy for isolating or eliciting antibodies against a specific target region on the envelope glycoprotein trimer (Env) of the human immunodeficiency virus type 1 (HIV-1) involves the creation of site transplants, which present the target region on a heterologous protein scaffold with preserved antibody-binding properties. 24992528 4 40 theme gp41 1015:1018 arg1 glycoprotein 1020:1031 the HIV-1 gp41 glycoprotein 1005:1031 the HIV-1 gp41 glycoprotein 1005:1031 To implement our strategy, we chose a single representative antibody against each of the target supersites: antibody 10E8, which recognizes the membrane-proximal external region (MPER) on the HIV-1 gp41 glycoprotein; antibody PG9, which recognizes variable regions one and two (V1V2) on the HIV-1 gp120 glycoprotein; and antibody PGT128 which recognizes a glycopeptide supersite in variable region 3 (glycan V3) on gp120. 24992528 3 41 from donors 809:814 arg1 antibodies 784:793 effective neutralizing antibodies 761:793 effective neutralizing antibodies from multiple donors 761:814 Here we transplant three supersites of HIV-1 vulnerability, each targeted by effective neutralizing antibodies from multiple donors. 24992528 1 42 theme specific 110:117 arg1 region 126:131 a specific target region 108:131 a specific target region on the envelope glycoprotein trimer (Env) of the human immunodeficiency virus type 1 (HIV-1) 108:224 One strategy for isolating or eliciting antibodies against a specific target region on the envelope glycoprotein trimer (Env) of the human immunodeficiency virus type 1 (HIV-1) involves the creation of site transplants, which present the target region on a heterologous protein scaffold with preserved antibody-binding properties. 24992528 5 43 theme structural 1249:1258 arg1 algorithm 1270:1278 a structural alignment algorithm 1247:1278 a structural alignment algorithm 1247:1278 We used a structural alignment algorithm to identify suitable acceptor proteins, and then designed, expressed, and tested antigenically over 100-supersite transplants in a 96-well microtiter-plate format. 24992528 0 44 theme vulnerability 34:46 arg1 supersites 14:23 supersites 14:23 supersites of HIV-1 vulnerability 14:46 Transplanting supersites of HIV-1 vulnerability. 24992528 1 45 theme target 287:292 arg1 region 294:299 the target region 283:299 the target region on a heterologous protein scaffold with preserved antibody-binding properties 283:377 One strategy for isolating or eliciting antibodies against a specific target region on the envelope glycoprotein trimer (Env) of the human immunodeficiency virus type 1 (HIV-1) involves the creation of site transplants, which present the target region on a heterologous protein scaffold with preserved antibody-binding properties. 24992528 9 46 theme immune-evading 2078:2091 arg1 capabilities 2093:2104 the immune-evading capabilities 2074:2104 the immune-evading capabilities of the rest of HIV-1 Env 2074:2129 Essential elements of the glycan V3 supersite, embodied by as few as 3 N-linked glycans and ∼ 25 Env residues, can be segregated into acceptor scaffolds away from the immune-evading capabilities of the rest of HIV-1 Env, thereby providing a means to focus the immune response on the scaffolded supersite. 24992528 4 47 theme variable 1065:1072 arg1 V1V2 1095:1098 V1V2 1095:1098 V1V2 1095:1098 To implement our strategy, we chose a single representative antibody against each of the target supersites: antibody 10E8, which recognizes the membrane-proximal external region (MPER) on the HIV-1 gp41 glycoprotein; antibody PG9, which recognizes variable regions one and two (V1V2) on the HIV-1 gp120 glycoprotein; and antibody PGT128 which recognizes a glycopeptide supersite in variable region 3 (glycan V3) on gp120. 24992528 4 47 theme variable 1065:1072 arg1 regions 1074:1080 variable regions one and two 1065:1092 variable regions one and two (V1V2) 1065:1099 To implement our strategy, we chose a single representative antibody against each of the target supersites: antibody 10E8, which recognizes the membrane-proximal external region (MPER) on the HIV-1 gp41 glycoprotein; antibody PG9, which recognizes variable regions one and two (V1V2) on the HIV-1 gp120 glycoprotein; and antibody PGT128 which recognizes a glycopeptide supersite in variable region 3 (glycan V3) on gp120. 24992528 4 48 theme glycan 1218:1223 arg1 V3 1225:1226 glycan V3 1218:1226 glycan V3 1218:1226 To implement our strategy, we chose a single representative antibody against each of the target supersites: antibody 10E8, which recognizes the membrane-proximal external region (MPER) on the HIV-1 gp41 glycoprotein; antibody PG9, which recognizes variable regions one and two (V1V2) on the HIV-1 gp120 glycoprotein; and antibody PGT128 which recognizes a glycopeptide supersite in variable region 3 (glycan V3) on gp120. 24992528 4 48 theme glycan 1218:1223 arg1 region 1208:1213 variable region 3 1199:1215 variable region 3 (glycan V3) on gp120 1199:1236 To implement our strategy, we chose a single representative antibody against each of the target supersites: antibody 10E8, which recognizes the membrane-proximal external region (MPER) on the HIV-1 gp41 glycoprotein; antibody PG9, which recognizes variable regions one and two (V1V2) on the HIV-1 gp120 glycoprotein; and antibody PGT128 which recognizes a glycopeptide supersite in variable region 3 (glycan V3) on gp120. 24992528 5 49 theme acceptor 1301:1308 arg1 proteins 1310:1317 suitable acceptor proteins 1292:1317 suitable acceptor proteins 1292:1317 We used a structural alignment algorithm to identify suitable acceptor proteins, and then designed, expressed, and tested antigenically over 100-supersite transplants in a 96-well microtiter-plate format. 24992528 4 50 theme glycopeptide 1173:1184 arg1 supersite 1186:1194 a glycopeptide supersite 1171:1194 a glycopeptide supersite 1171:1194 To implement our strategy, we chose a single representative antibody against each of the target supersites: antibody 10E8, which recognizes the membrane-proximal external region (MPER) on the HIV-1 gp41 glycoprotein; antibody PG9, which recognizes variable regions one and two (V1V2) on the HIV-1 gp120 glycoprotein; and antibody PGT128 which recognizes a glycopeptide supersite in variable region 3 (glycan V3) on gp120. 24992528 5 51 from transplants 1394:1404 arg1 format 1436:1441 a 96-well microtiter-plate format 1409:1441 a 96-well microtiter-plate format 1409:1441 We used a structural alignment algorithm to identify suitable acceptor proteins, and then designed, expressed, and tested antigenically over 100-supersite transplants in a 96-well microtiter-plate format. 24992528 9 52 theme rest 2113:2116 arg1 capabilities 2093:2104 the immune-evading capabilities 2074:2104 the immune-evading capabilities of the rest of HIV-1 Env 2074:2129 Essential elements of the glycan V3 supersite, embodied by as few as 3 N-linked glycans and ∼ 25 Env residues, can be segregated into acceptor scaffolds away from the immune-evading capabilities of the rest of HIV-1 Env, thereby providing a means to focus the immune response on the scaffolded supersite. 24992528 9 53 theme Essential 1911:1919 arg1 elements 1921:1928 Essential elements 1911:1928 Essential elements 1911:1928 Essential elements of the glycan V3 supersite, embodied by as few as 3 N-linked glycans and ∼ 25 Env residues, can be segregated into acceptor scaffolds away from the immune-evading capabilities of the rest of HIV-1 Env, thereby providing a means to focus the immune response on the scaffolded supersite. 24992528 9 54 theme HIV-1 2121:2125 arg1 Env 2127:2129 HIV-1 Env 2121:2129 HIV-1 Env 2121:2129 Essential elements of the glycan V3 supersite, embodied by as few as 3 N-linked glycans and ∼ 25 Env residues, can be segregated into acceptor scaffolds away from the immune-evading capabilities of the rest of HIV-1 Env, thereby providing a means to focus the immune response on the scaffolded supersite. 24992528 8 55 theme self-assembling 1880:1894 arg1 nanoparticles 1896:1908 self-assembling nanoparticles 1880:1908 self-assembling nanoparticles 1880:1908 The binding of these transplants could be further enhanced by placement into self-assembling nanoparticles. 24992528 9 56 theme ∼ 2003:2003 arg1 residues 2012:2019 ∼ 25 Env residues 2003:2019 ∼ 25 Env residues 2003:2019 Essential elements of the glycan V3 supersite, embodied by as few as 3 N-linked glycans and ∼ 25 Env residues, can be segregated into acceptor scaffolds away from the immune-evading capabilities of the rest of HIV-1 Env, thereby providing a means to focus the immune response on the scaffolded supersite. 24992528 4 57 theme single 855:860 arg1 antibody 877:884 a single representative antibody 853:884 a single representative antibody against each of the target supersites 853:922 To implement our strategy, we chose a single representative antibody against each of the target supersites: antibody 10E8, which recognizes the membrane-proximal external region (MPER) on the HIV-1 gp41 glycoprotein; antibody PG9, which recognizes variable regions one and two (V1V2) on the HIV-1 gp120 glycoprotein; and antibody PGT128 which recognizes a glycopeptide supersite in variable region 3 (glycan V3) on gp120. 24992528 7 58 theme template 1783:1790 arg1 supersite 1792:1800 the template supersite 1779:1800 the template supersite 1779:1800 However, seven of the glycan V3-supersite transplants exhibited nanomolar affinity to effective neutralizing antibodies from at least three donors and recapitulated the mannose9-N-linked glycan requirement of the template supersite. 24992528 7 59 from donors 1710:1715 arg1 antibodies 1679:1688 effective neutralizing antibodies 1656:1688 effective neutralizing antibodies from at least three donors 1656:1715 However, seven of the glycan V3-supersite transplants exhibited nanomolar affinity to effective neutralizing antibodies from at least three donors and recapitulated the mannose9-N-linked glycan requirement of the template supersite. 24992528 9 60 theme glycan 1937:1942 arg1 supersite 1947:1955 the glycan V3 supersite 1933:1955 the glycan V3 supersite 1933:1955 Essential elements of the glycan V3 supersite, embodied by as few as 3 N-linked glycans and ∼ 25 Env residues, can be segregated into acceptor scaffolds away from the immune-evading capabilities of the rest of HIV-1 Env, thereby providing a means to focus the immune response on the scaffolded supersite. 24992528 7 61 theme V3-supersite 1599:1610 arg1 transplants 1612:1622 the glycan V3-supersite transplants 1588:1622 the glycan V3-supersite transplants 1588:1622 However, seven of the glycan V3-supersite transplants exhibited nanomolar affinity to effective neutralizing antibodies from at least three donors and recapitulated the mannose9-N-linked glycan requirement of the template supersite. 24992528 7 62 theme glycan 1757:1762 arg1 requirement 1764:1774 the mannose9-N-linked glycan requirement 1735:1774 the mannose9-N-linked glycan requirement of the template supersite 1735:1800 However, seven of the glycan V3-supersite transplants exhibited nanomolar affinity to effective neutralizing antibodies from at least three donors and recapitulated the mannose9-N-linked glycan requirement of the template supersite. 24992528 9 63 theme supersite 1947:1955 arg1 elements 1921:1928 Essential elements 1911:1928 Essential elements 1911:1928 Essential elements of the glycan V3 supersite, embodied by as few as 3 N-linked glycans and ∼ 25 Env residues, can be segregated into acceptor scaffolds away from the immune-evading capabilities of the rest of HIV-1 Env, thereby providing a means to focus the immune response on the scaffolded supersite. 24992528 6 64 theme supersite 1464:1472 arg1 transplants 1474:1484 the supersite transplants 1460:1484 the supersite transplants 1460:1484 The majority of the supersite transplants failed to maintain the antigenic properties of their respective template supersite. 24992528 1 65 theme human 182:186 arg1 HIV-1 219:223 HIV-1 219:223 HIV-1 219:223 One strategy for isolating or eliciting antibodies against a specific target region on the envelope glycoprotein trimer (Env) of the human immunodeficiency virus type 1 (HIV-1) involves the creation of site transplants, which present the target region on a heterologous protein scaffold with preserved antibody-binding properties. 24992528 1 65 theme human 182:186 arg1 type 211:214 the human immunodeficiency virus type 1 178:216 the human immunodeficiency virus type 1 (HIV-1) 178:224 One strategy for isolating or eliciting antibodies against a specific target region on the envelope glycoprotein trimer (Env) of the human immunodeficiency virus type 1 (HIV-1) involves the creation of site transplants, which present the target region on a heterologous protein scaffold with preserved antibody-binding properties. 24992528 9 66 link N-linked 1982:1989 arg1 glycans 1991:1997 as few as 3 N-linked glycans 1970:1997 as few as 3 N-linked glycans 1970:1997 Essential elements of the glycan V3 supersite, embodied by as few as 3 N-linked glycans and ∼ 25 Env residues, can be segregated into acceptor scaffolds away from the immune-evading capabilities of the rest of HIV-1 Env, thereby providing a means to focus the immune response on the scaffolded supersite. 24992528 3 67 theme HIV-1 723:727 arg1 vulnerability 729:741 HIV-1 vulnerability 723:741 HIV-1 vulnerability 723:741 Here we transplant three supersites of HIV-1 vulnerability, each targeted by effective neutralizing antibodies from multiple donors. 24992528 1 68 theme virus 205:209 arg1 HIV-1 219:223 HIV-1 219:223 HIV-1 219:223 One strategy for isolating or eliciting antibodies against a specific target region on the envelope glycoprotein trimer (Env) of the human immunodeficiency virus type 1 (HIV-1) involves the creation of site transplants, which present the target region on a heterologous protein scaffold with preserved antibody-binding properties. 24992528 1 68 theme virus 205:209 arg1 type 211:214 the human immunodeficiency virus type 1 178:216 the human immunodeficiency virus type 1 (HIV-1) 178:224 One strategy for isolating or eliciting antibodies against a specific target region on the envelope glycoprotein trimer (Env) of the human immunodeficiency virus type 1 (HIV-1) involves the creation of site transplants, which present the target region on a heterologous protein scaffold with preserved antibody-binding properties. 24992528 4 69 gly glycoprotein 1120:1131 arg1 glycoprotein 1120:1131 the HIV-1 gp120 glycoprotein 1104:1131 the HIV-1 gp120 glycoprotein 1104:1131 To implement our strategy, we chose a single representative antibody against each of the target supersites: antibody 10E8, which recognizes the membrane-proximal external region (MPER) on the HIV-1 gp41 glycoprotein; antibody PG9, which recognizes variable regions one and two (V1V2) on the HIV-1 gp120 glycoprotein; and antibody PGT128 which recognizes a glycopeptide supersite in variable region 3 (glycan V3) on gp120. 24992528 3 70 theme effective 761:769 arg1 antibodies 784:793 effective neutralizing antibodies 761:793 effective neutralizing antibodies from multiple donors 761:814 Here we transplant three supersites of HIV-1 vulnerability, each targeted by effective neutralizing antibodies from multiple donors. 24992528 1 71 gly glycoprotein 149:160 arg1 glycoprotein 149:160 the envelope glycoprotein trimer 136:167 the envelope glycoprotein trimer (Env) of the human immunodeficiency virus type 1 (HIV-1) 136:224 One strategy for isolating or eliciting antibodies against a specific target region on the envelope glycoprotein trimer (Env) of the human immunodeficiency virus type 1 (HIV-1) involves the creation of site transplants, which present the target region on a heterologous protein scaffold with preserved antibody-binding properties. 24992528 6 72 theme supersite 1559:1567 arg1 properties 1519:1528 the antigenic properties 1505:1528 the antigenic properties of their respective template supersite 1505:1567 The majority of the supersite transplants failed to maintain the antigenic properties of their respective template supersite. 24992528 1 73 theme target 119:124 arg1 region 126:131 a specific target region 108:131 a specific target region on the envelope glycoprotein trimer (Env) of the human immunodeficiency virus type 1 (HIV-1) 108:224 One strategy for isolating or eliciting antibodies against a specific target region on the envelope glycoprotein trimer (Env) of the human immunodeficiency virus type 1 (HIV-1) involves the creation of site transplants, which present the target region on a heterologous protein scaffold with preserved antibody-binding properties. 24992528 2 74 theme transplants 552:562 arg1 " 563:563 "supersite transplants" 541:563 "supersite transplants" 541:563 If the target region is a supersite of HIV-1 vulnerability, recognized by a collection of broadly neutralizing antibodies, this strategy affords the creation of "supersite transplants", capable of binding (and potentially eliciting) antibodies similar to the template collection of effective antibodies. 24992528 2 75 theme antibodies 672:681 arg1 collection 648:657 the template collection 635:657 the template collection of effective antibodies 635:681 If the target region is a supersite of HIV-1 vulnerability, recognized by a collection of broadly neutralizing antibodies, this strategy affords the creation of "supersite transplants", capable of binding (and potentially eliciting) antibodies similar to the template collection of effective antibodies. 24992528 6 76 theme respective 1539:1548 arg1 supersite 1559:1567 their respective template supersite 1533:1567 their respective template supersite 1533:1567 The majority of the supersite transplants failed to maintain the antigenic properties of their respective template supersite. 24992528 7 77 theme mannose9-N-linked 1739:1755 arg1 requirement 1764:1774 the mannose9-N-linked glycan requirement 1735:1774 the mannose9-N-linked glycan requirement of the template supersite 1735:1800 However, seven of the glycan V3-supersite transplants exhibited nanomolar affinity to effective neutralizing antibodies from at least three donors and recapitulated the mannose9-N-linked glycan requirement of the template supersite. 24992528 4 78 theme HIV-1 1108:1112 arg1 glycoprotein 1120:1131 the HIV-1 gp120 glycoprotein 1104:1131 the HIV-1 gp120 glycoprotein 1104:1131 To implement our strategy, we chose a single representative antibody against each of the target supersites: antibody 10E8, which recognizes the membrane-proximal external region (MPER) on the HIV-1 gp41 glycoprotein; antibody PG9, which recognizes variable regions one and two (V1V2) on the HIV-1 gp120 glycoprotein; and antibody PGT128 which recognizes a glycopeptide supersite in variable region 3 (glycan V3) on gp120. 24992528 3 79 theme multiple 800:807 arg1 donors 809:814 multiple donors 800:814 multiple donors 800:814 Here we transplant three supersites of HIV-1 vulnerability, each targeted by effective neutralizing antibodies from multiple donors. 24992528 7 80 link mannose9-N-linked 1739:1755 arg1 requirement 1764:1774 the mannose9-N-linked glycan requirement 1735:1774 the mannose9-N-linked glycan requirement of the template supersite 1735:1800 However, seven of the glycan V3-supersite transplants exhibited nanomolar affinity to effective neutralizing antibodies from at least three donors and recapitulated the mannose9-N-linked glycan requirement of the template supersite. 24992528 1 81 theme envelope 140:147 arg1 Env 170:172 Env 170:172 Env 170:172 One strategy for isolating or eliciting antibodies against a specific target region on the envelope glycoprotein trimer (Env) of the human immunodeficiency virus type 1 (HIV-1) involves the creation of site transplants, which present the target region on a heterologous protein scaffold with preserved antibody-binding properties. 24992528 1 81 theme envelope 140:147 arg1 trimer 162:167 the envelope glycoprotein trimer 136:167 the envelope glycoprotein trimer (Env) of the human immunodeficiency virus type 1 (HIV-1) 136:224 One strategy for isolating or eliciting antibodies against a specific target region on the envelope glycoprotein trimer (Env) of the human immunodeficiency virus type 1 (HIV-1) involves the creation of site transplants, which present the target region on a heterologous protein scaffold with preserved antibody-binding properties. 24992528 6 82 theme antigenic 1509:1517 arg1 properties 1519:1528 the antigenic properties 1505:1528 the antigenic properties of their respective template supersite 1505:1567 The majority of the supersite transplants failed to maintain the antigenic properties of their respective template supersite. 24992528 4 83 theme membrane-proximal 961:977 arg1 MPER 996:999 MPER 996:999 MPER 996:999 To implement our strategy, we chose a single representative antibody against each of the target supersites: antibody 10E8, which recognizes the membrane-proximal external region (MPER) on the HIV-1 gp41 glycoprotein; antibody PG9, which recognizes variable regions one and two (V1V2) on the HIV-1 gp120 glycoprotein; and antibody PGT128 which recognizes a glycopeptide supersite in variable region 3 (glycan V3) on gp120. 24992528 4 83 theme membrane-proximal 961:977 arg1 region 988:993 the membrane-proximal external region 957:993 the membrane-proximal external region (MPER) on the HIV-1 gp41 glycoprotein 957:1031 To implement our strategy, we chose a single representative antibody against each of the target supersites: antibody 10E8, which recognizes the membrane-proximal external region (MPER) on the HIV-1 gp41 glycoprotein; antibody PG9, which recognizes variable regions one and two (V1V2) on the HIV-1 gp120 glycoprotein; and antibody PGT128 which recognizes a glycopeptide supersite in variable region 3 (glycan V3) on gp120. 24992528 1 84 theme protein 319:325 arg1 scaffold 327:334 a heterologous protein scaffold 304:334 a heterologous protein scaffold with preserved antibody-binding properties 304:377 One strategy for isolating or eliciting antibodies against a specific target region on the envelope glycoprotein trimer (Env) of the human immunodeficiency virus type 1 (HIV-1) involves the creation of site transplants, which present the target region on a heterologous protein scaffold with preserved antibody-binding properties. 24992528 4 85 from region 1208:1213 arg1 gp120 1232:1236 gp120 1232:1236 gp120 1232:1236 To implement our strategy, we chose a single representative antibody against each of the target supersites: antibody 10E8, which recognizes the membrane-proximal external region (MPER) on the HIV-1 gp41 glycoprotein; antibody PG9, which recognizes variable regions one and two (V1V2) on the HIV-1 gp120 glycoprotein; and antibody PGT128 which recognizes a glycopeptide supersite in variable region 3 (glycan V3) on gp120. 24992528 4 86 theme antibody 925:932 arg1 10E8 934:937 antibody 10E8 925:937 antibody 10E8 925:937 To implement our strategy, we chose a single representative antibody against each of the target supersites: antibody 10E8, which recognizes the membrane-proximal external region (MPER) on the HIV-1 gp41 glycoprotein; antibody PG9, which recognizes variable regions one and two (V1V2) on the HIV-1 gp120 glycoprotein; and antibody PGT128 which recognizes a glycopeptide supersite in variable region 3 (glycan V3) on gp120. 24992528 5 87 used used 1242:1245 arg2 We 1239:1240 We 1239:1240 We 1239:1240 We used a structural alignment algorithm to identify suitable acceptor proteins, and then designed, expressed, and tested antigenically over 100-supersite transplants in a 96-well microtiter-plate format. 24992528 5 88 theme alignment 1260:1268 arg1 algorithm 1270:1278 a structural alignment algorithm 1247:1278 a structural alignment algorithm 1247:1278 We used a structural alignment algorithm to identify suitable acceptor proteins, and then designed, expressed, and tested antigenically over 100-supersite transplants in a 96-well microtiter-plate format. 24992528 2 89 theme antibodies 491:500 arg1 collection 456:465 a collection 454:465 a collection of broadly neutralizing antibodies 454:500 If the target region is a supersite of HIV-1 vulnerability, recognized by a collection of broadly neutralizing antibodies, this strategy affords the creation of "supersite transplants", capable of binding (and potentially eliciting) antibodies similar to the template collection of effective antibodies. 24992528 1 90 theme antibody-binding 351:366 arg1 properties 368:377 preserved antibody-binding properties 341:377 preserved antibody-binding properties 341:377 One strategy for isolating or eliciting antibodies against a specific target region on the envelope glycoprotein trimer (Env) of the human immunodeficiency virus type 1 (HIV-1) involves the creation of site transplants, which present the target region on a heterologous protein scaffold with preserved antibody-binding properties. 24992528 7 91 theme neutralizing 1666:1677 arg1 antibodies 1679:1688 effective neutralizing antibodies 1656:1688 effective neutralizing antibodies from at least three donors 1656:1715 However, seven of the glycan V3-supersite transplants exhibited nanomolar affinity to effective neutralizing antibodies from at least three donors and recapitulated the mannose9-N-linked glycan requirement of the template supersite. 24992528 2 92 theme HIV-1 419:423 arg1 vulnerability 425:437 HIV-1 vulnerability 419:437 HIV-1 vulnerability 419:437 If the target region is a supersite of HIV-1 vulnerability, recognized by a collection of broadly neutralizing antibodies, this strategy affords the creation of "supersite transplants", capable of binding (and potentially eliciting) antibodies similar to the template collection of effective antibodies. 24992528 5 93 theme microtiter-plate 1419:1434 arg1 format 1436:1441 a 96-well microtiter-plate format 1409:1441 a 96-well microtiter-plate format 1409:1441 We used a structural alignment algorithm to identify suitable acceptor proteins, and then designed, expressed, and tested antigenically over 100-supersite transplants in a 96-well microtiter-plate format. 24992528 2 94 theme template 639:646 arg1 collection 648:657 the template collection 635:657 the template collection of effective antibodies 635:681 If the target region is a supersite of HIV-1 vulnerability, recognized by a collection of broadly neutralizing antibodies, this strategy affords the creation of "supersite transplants", capable of binding (and potentially eliciting) antibodies similar to the template collection of effective antibodies. 24992528 0 95 theme HIV-1 28:32 arg1 vulnerability 34:46 HIV-1 vulnerability 28:46 HIV-1 vulnerability 28:46 Transplanting supersites of HIV-1 vulnerability. 24992528 1 96 theme transplants 256:266 arg1 creation 239:246 the creation 235:246 the creation 235:246 One strategy for isolating or eliciting antibodies against a specific target region on the envelope glycoprotein trimer (Env) of the human immunodeficiency virus type 1 (HIV-1) involves the creation of site transplants, which present the target region on a heterologous protein scaffold with preserved antibody-binding properties. 24992528 1 97 from region 126:131 arg1 Env 170:172 Env 170:172 Env 170:172 One strategy for isolating or eliciting antibodies against a specific target region on the envelope glycoprotein trimer (Env) of the human immunodeficiency virus type 1 (HIV-1) involves the creation of site transplants, which present the target region on a heterologous protein scaffold with preserved antibody-binding properties. 24992528 1 97 from region 126:131 arg1 trimer 162:167 the envelope glycoprotein trimer 136:167 the envelope glycoprotein trimer (Env) of the human immunodeficiency virus type 1 (HIV-1) 136:224 One strategy for isolating or eliciting antibodies against a specific target region on the envelope glycoprotein trimer (Env) of the human immunodeficiency virus type 1 (HIV-1) involves the creation of site transplants, which present the target region on a heterologous protein scaffold with preserved antibody-binding properties. 24992528 4 98 theme HIV-1 1009:1013 arg1 glycoprotein 1020:1031 the HIV-1 gp41 glycoprotein 1005:1031 the HIV-1 gp41 glycoprotein 1005:1031 To implement our strategy, we chose a single representative antibody against each of the target supersites: antibody 10E8, which recognizes the membrane-proximal external region (MPER) on the HIV-1 gp41 glycoprotein; antibody PG9, which recognizes variable regions one and two (V1V2) on the HIV-1 gp120 glycoprotein; and antibody PGT128 which recognizes a glycopeptide supersite in variable region 3 (glycan V3) on gp120. 24992528 9 99 theme acceptor 2045:2052 arg1 scaffolds 2054:2062 acceptor scaffolds 2045:2062 acceptor scaffolds 2045:2062 Essential elements of the glycan V3 supersite, embodied by as few as 3 N-linked glycans and ∼ 25 Env residues, can be segregated into acceptor scaffolds away from the immune-evading capabilities of the rest of HIV-1 Env, thereby providing a means to focus the immune response on the scaffolded supersite. 24992528 7 100 theme nanomolar 1634:1642 arg1 affinity 1644:1651 nanomolar affinity 1634:1651 nanomolar affinity to effective neutralizing antibodies from at least three donors 1634:1715 However, seven of the glycan V3-supersite transplants exhibited nanomolar affinity to effective neutralizing antibodies from at least three donors and recapitulated the mannose9-N-linked glycan requirement of the template supersite. 24992528 2 101 theme target 387:392 arg1 region 394:399 the target region 383:399 the target region 383:399 If the target region is a supersite of HIV-1 vulnerability, recognized by a collection of broadly neutralizing antibodies, this strategy affords the creation of "supersite transplants", capable of binding (and potentially eliciting) antibodies similar to the template collection of effective antibodies. 24992528 2 101 theme target 387:392 arg1 supersite 406:414 a supersite 404:414 a supersite 404:414 If the target region is a supersite of HIV-1 vulnerability, recognized by a collection of broadly neutralizing antibodies, this strategy affords the creation of "supersite transplants", capable of binding (and potentially eliciting) antibodies similar to the template collection of effective antibodies. 24992528 2 101 theme target 387:392 arg1 vulnerability 425:437 HIV-1 vulnerability 419:437 HIV-1 vulnerability 419:437 If the target region is a supersite of HIV-1 vulnerability, recognized by a collection of broadly neutralizing antibodies, this strategy affords the creation of "supersite transplants", capable of binding (and potentially eliciting) antibodies similar to the template collection of effective antibodies. 24992528 4 102 from region 988:993 arg1 glycoprotein 1020:1031 the HIV-1 gp41 glycoprotein 1005:1031 the HIV-1 gp41 glycoprotein 1005:1031 To implement our strategy, we chose a single representative antibody against each of the target supersites: antibody 10E8, which recognizes the membrane-proximal external region (MPER) on the HIV-1 gp41 glycoprotein; antibody PG9, which recognizes variable regions one and two (V1V2) on the HIV-1 gp120 glycoprotein; and antibody PGT128 which recognizes a glycopeptide supersite in variable region 3 (glycan V3) on gp120. 24992528 5 103 theme suitable 1292:1299 arg1 proteins 1310:1317 suitable acceptor proteins 1292:1317 suitable acceptor proteins 1292:1317 We used a structural alignment algorithm to identify suitable acceptor proteins, and then designed, expressed, and tested antigenically over 100-supersite transplants in a 96-well microtiter-plate format. 24992528 9 104 theme immune 2171:2176 arg1 response 2178:2185 the immune response 2167:2185 the immune response 2167:2185 Essential elements of the glycan V3 supersite, embodied by as few as 3 N-linked glycans and ∼ 25 Env residues, can be segregated into acceptor scaffolds away from the immune-evading capabilities of the rest of HIV-1 Env, thereby providing a means to focus the immune response on the scaffolded supersite. 28100622 7 0 theme human 1491:1495 arg1 health 1497:1502 human health 1491:1502 human health 1491:1502 These findings further our understanding of the determinants of pathogenicity of H5N1 viruses in mammals.IMPORTANCE Highly pathogenic avian influenza (HPAI) H5N1 viruses continue to evolve in nature and threaten human health. 28100622 7 1 from determinants 1327:1338 arg1 viruses 1441:1447 mammals.IMPORTANCE Highly pathogenic avian influenza (HPAI) H5N1 viruses 1376:1447 mammals.IMPORTANCE Highly pathogenic avian influenza (HPAI) H5N1 viruses 1376:1447 These findings further our understanding of the determinants of pathogenicity of H5N1 viruses in mammals.IMPORTANCE Highly pathogenic avian influenza (HPAI) H5N1 viruses continue to evolve in nature and threaten human health. 28100622 7 2 theme H5N1 1436:1439 arg1 viruses 1441:1447 mammals.IMPORTANCE Highly pathogenic avian influenza (HPAI) H5N1 viruses 1376:1447 mammals.IMPORTANCE Highly pathogenic avian influenza (HPAI) H5N1 viruses 1376:1447 These findings further our understanding of the determinants of pathogenicity of H5N1 viruses in mammals.IMPORTANCE Highly pathogenic avian influenza (HPAI) H5N1 viruses continue to evolve in nature and threaten human health. 28100622 10 3 theme important 2058:2066 arg1 glycosylation 1956:1968 glycosylation 1956:1968 glycosylation at positions 158 to 160 of the HA protein of two naturally occurring H5N1 viruses 1956:2050 In this study, we identified glycosylation at positions 158 to 160 of the HA protein of two naturally occurring H5N1 viruses as an important virulence determinant. 28100622 10 3 theme important 2058:2066 arg1 determinant 2078:2088 an important virulence determinant 2055:2088 an important virulence determinant 2055:2088 In this study, we identified glycosylation at positions 158 to 160 of the HA protein of two naturally occurring H5N1 viruses as an important virulence determinant. 28100622 3 4 from lethality 637:645 arg1 mice 650:653 mice 650:653 mice 650:653 In our previous studies, we characterized two naturally isolated HPAI H5N1 viruses that had similar viral genomes but differed substantially in their lethality in mice. 28100622 3 5 theme isolated 543:550 arg1 viruses 562:568 two naturally isolated HPAI H5N1 viruses 529:568 two naturally isolated HPAI H5N1 viruses that had similar viral genomes but differed substantially in their lethality in mice 529:653 In our previous studies, we characterized two naturally isolated HPAI H5N1 viruses that had similar viral genomes but differed substantially in their lethality in mice. 28100622 7 6 theme HPAI 1430:1433 arg1 viruses 1441:1447 mammals.IMPORTANCE Highly pathogenic avian influenza (HPAI) H5N1 viruses 1376:1447 mammals.IMPORTANCE Highly pathogenic avian influenza (HPAI) H5N1 viruses 1376:1447 These findings further our understanding of the determinants of pathogenicity of H5N1 viruses in mammals.IMPORTANCE Highly pathogenic avian influenza (HPAI) H5N1 viruses continue to evolve in nature and threaten human health. 28100622 6 7 theme inflammatory 1236:1247 arg1 responses 1249:1257 host immune and inflammatory responses 1220:1257 stronger host immune and inflammatory responses to viral infection 1211:1276 We further found that the G158N mutation introduced an N-linked glycosylation at positions 158 to 160 of the HA protein and that this N-linked glycosylation enhanced viral productivity in infected mammalian cells and induced stronger host immune and inflammatory responses to viral infection. 28100622 1 8 theme influenza 169:177 arg1 viruses 191:197 The highly pathogenic avian influenza (HPAI) H5N1 viruses 141:197 The highly pathogenic avian influenza (HPAI) H5N1 viruses 141:197 The highly pathogenic avian influenza (HPAI) H5N1 viruses continue to circulate in nature and threaten public health. 28100622 11 9 theme viral 2125:2129 arg1 productivity 2131:2142 viral productivity 2125:2142 viral productivity 2125:2142 This glycosylation event enhanced viral productivity, exacerbated the host response, and thereby contributed to the high pathogenicity of H5N1 virus in mice. 28100622 7 10 theme influenza 1419:1427 arg1 viruses 1441:1447 mammals.IMPORTANCE Highly pathogenic avian influenza (HPAI) H5N1 viruses 1376:1447 mammals.IMPORTANCE Highly pathogenic avian influenza (HPAI) H5N1 viruses 1376:1447 These findings further our understanding of the determinants of pathogenicity of H5N1 viruses in mammals.IMPORTANCE Highly pathogenic avian influenza (HPAI) H5N1 viruses continue to evolve in nature and threaten human health. 28100622 6 11 theme immune 1225:1230 arg1 responses 1249:1257 host immune and inflammatory responses 1220:1257 stronger host immune and inflammatory responses to viral infection 1211:1276 We further found that the G158N mutation introduced an N-linked glycosylation at positions 158 to 160 of the HA protein and that this N-linked glycosylation enhanced viral productivity in infected mammalian cells and induced stronger host immune and inflammatory responses to viral infection. 28100622 2 12 theme host 299:302 arg1 factors 304:310 host factors 299:310 host factors 299:310 Although several viral determinants and host factors that influence the virulence of HPAI H5N1 viruses in mammals have been identified, the detailed molecular mechanism remains poorly defined and requires further clarification. 28100622 1 13 theme HPAI 180:183 arg1 viruses 191:197 The highly pathogenic avian influenza (HPAI) H5N1 viruses 141:197 The highly pathogenic avian influenza (HPAI) H5N1 viruses 141:197 The highly pathogenic avian influenza (HPAI) H5N1 viruses continue to circulate in nature and threaten public health. 28100622 9 14 theme thorough 1689:1696 arg1 understanding 1698:1710 A thorough understanding 1687:1710 A thorough understanding of the pathogenic mechanisms of these viruses 1687:1756 A thorough understanding of the pathogenic mechanisms of these viruses will help us to develop more effective control strategies; however, such mechanisms and virulent determinants for H5N1 influenza viruses have not been fully elucidated. 28100622 7 15 theme pathogenic 1402:1411 arg1 viruses 1441:1447 mammals.IMPORTANCE Highly pathogenic avian influenza (HPAI) H5N1 viruses 1376:1447 mammals.IMPORTANCE Highly pathogenic avian influenza (HPAI) H5N1 viruses 1376:1447 These findings further our understanding of the determinants of pathogenicity of H5N1 viruses in mammals.IMPORTANCE Highly pathogenic avian influenza (HPAI) H5N1 viruses continue to evolve in nature and threaten human health. 28100622 3 16 theme H5N1 557:560 arg1 viruses 562:568 two naturally isolated HPAI H5N1 viruses 529:568 two naturally isolated HPAI H5N1 viruses that had similar viral genomes but differed substantially in their lethality in mice 529:653 In our previous studies, we characterized two naturally isolated HPAI H5N1 viruses that had similar viral genomes but differed substantially in their lethality in mice. 28100622 5 17 theme amino 818:822 arg1 acid 824:827 a single amino acid 809:827 a single amino acid at position 158 of the hemagglutinin (HA) protein 809:877 By using reverse genetics, we found that a single amino acid at position 158 of the hemagglutinin (HA) protein substantially affected the systemic replication and pathogenicity of these H5N1 influenza viruses in mice. 28100622 6 18 theme host 1220:1223 arg1 responses 1249:1257 host immune and inflammatory responses 1220:1257 stronger host immune and inflammatory responses to viral infection 1211:1276 We further found that the G158N mutation introduced an N-linked glycosylation at positions 158 to 160 of the HA protein and that this N-linked glycosylation enhanced viral productivity in infected mammalian cells and induced stronger host immune and inflammatory responses to viral infection. 28100622 0 19 theme Immune 124:129 arg1 Response 131:138 the Host Immune Response 115:138 the Host Immune Response 115:138 Glycosylation of the Hemagglutinin Protein of H5N1 Influenza Virus Increases Its Virulence in Mice by Exacerbating the Host Immune Response. 28100622 9 20 theme pathogenic 1719:1728 arg1 mechanisms 1730:1739 the pathogenic mechanisms 1715:1739 the pathogenic mechanisms of these viruses 1715:1756 A thorough understanding of the pathogenic mechanisms of these viruses will help us to develop more effective control strategies; however, such mechanisms and virulent determinants for H5N1 influenza viruses have not been fully elucidated. 28100622 7 21 theme viruses 1365:1371 arg1 pathogenicity 1343:1355 pathogenicity 1343:1355 pathogenicity of H5N1 viruses in mammals.IMPORTANCE Highly pathogenic avian influenza (HPAI) H5N1 viruses 1343:1447 These findings further our understanding of the determinants of pathogenicity of H5N1 viruses in mammals.IMPORTANCE Highly pathogenic avian influenza (HPAI) H5N1 viruses continue to evolve in nature and threaten human health. 28100622 3 22 theme similar 579:585 arg1 genomes 593:599 similar viral genomes 579:599 similar viral genomes 579:599 In our previous studies, we characterized two naturally isolated HPAI H5N1 viruses that had similar viral genomes but differed substantially in their lethality in mice. 28100622 4 23 theme potential 714:722 arg1 mechanism 724:732 potential mechanism 714:732 potential mechanism 714:732 In this study, we explored the molecular determinants and potential mechanism for this difference in virulence. 28100622 10 24 theme protein 2004:2010 arg1 glycosylation 1956:1968 glycosylation 1956:1968 glycosylation at positions 158 to 160 of the HA protein of two naturally occurring H5N1 viruses 1956:2050 In this study, we identified glycosylation at positions 158 to 160 of the HA protein of two naturally occurring H5N1 viruses as an important virulence determinant. 28100622 10 24 theme protein 2004:2010 arg1 determinant 2078:2088 an important virulence determinant 2055:2088 an important virulence determinant 2055:2088 In this study, we identified glycosylation at positions 158 to 160 of the HA protein of two naturally occurring H5N1 viruses as an important virulence determinant. 28100622 9 25 theme viruses 1750:1756 arg1 mechanisms 1730:1739 the pathogenic mechanisms 1715:1739 the pathogenic mechanisms of these viruses 1715:1756 A thorough understanding of the pathogenic mechanisms of these viruses will help us to develop more effective control strategies; however, such mechanisms and virulent determinants for H5N1 influenza viruses have not been fully elucidated. 28100622 6 26 theme infected 1174:1181 arg1 cells 1193:1197 infected mammalian cells 1174:1197 infected mammalian cells 1174:1197 We further found that the G158N mutation introduced an N-linked glycosylation at positions 158 to 160 of the HA protein and that this N-linked glycosylation enhanced viral productivity in infected mammalian cells and induced stronger host immune and inflammatory responses to viral infection. 28100622 0 27 theme Virus 61:65 arg1 Protein 35:41 the Hemagglutinin Protein 17:41 the Hemagglutinin Protein of H5N1 Influenza Virus 17:65 Glycosylation of the Hemagglutinin Protein of H5N1 Influenza Virus Increases Its Virulence in Mice by Exacerbating the Host Immune Response. 28100622 11 28 theme host 2161:2164 arg1 response 2166:2173 the host response 2157:2173 the host response 2157:2173 This glycosylation event enhanced viral productivity, exacerbated the host response, and thereby contributed to the high pathogenicity of H5N1 virus in mice. 28100622 5 29 from position 832:839 arg1 acid 824:827 a single amino acid 809:827 a single amino acid at position 158 of the hemagglutinin (HA) protein 809:877 By using reverse genetics, we found that a single amino acid at position 158 of the hemagglutinin (HA) protein substantially affected the systemic replication and pathogenicity of these H5N1 influenza viruses in mice. 28100622 10 30 theme occurring 2029:2037 arg1 viruses 2044:2050 two naturally occurring H5N1 viruses 2015:2050 two naturally occurring H5N1 viruses 2015:2050 In this study, we identified glycosylation at positions 158 to 160 of the HA protein of two naturally occurring H5N1 viruses as an important virulence determinant. 28100622 1 31 theme pathogenic 152:161 arg1 viruses 191:197 The highly pathogenic avian influenza (HPAI) H5N1 viruses 141:197 The highly pathogenic avian influenza (HPAI) H5N1 viruses 141:197 The highly pathogenic avian influenza (HPAI) H5N1 viruses continue to circulate in nature and threaten public health. 28100622 6 32 theme mammalian 1183:1191 arg1 cells 1193:1197 infected mammalian cells 1174:1197 infected mammalian cells 1174:1197 We further found that the G158N mutation introduced an N-linked glycosylation at positions 158 to 160 of the HA protein and that this N-linked glycosylation enhanced viral productivity in infected mammalian cells and induced stronger host immune and inflammatory responses to viral infection. 28100622 8 33 from transmissibility 1658:1673 arg1 mammals 1678:1684 mammals 1678:1684 mammals 1678:1684 Key mutations in the virus hemagglutinin (HA) protein or reassortment with other pandemic viruses endow HPAI H5N1 viruses with the potential for aerosol transmissibility in mammals. 28100622 6 34 link N-linked 1120:1127 arg1 glycosylation 1129:1141 this N-linked glycosylation 1115:1141 this N-linked glycosylation 1115:1141 We further found that the G158N mutation introduced an N-linked glycosylation at positions 158 to 160 of the HA protein and that this N-linked glycosylation enhanced viral productivity in infected mammalian cells and induced stronger host immune and inflammatory responses to viral infection. 28100622 2 35 theme several 268:274 arg1 determinants 282:293 several viral determinants 268:293 several viral determinants 268:293 Although several viral determinants and host factors that influence the virulence of HPAI H5N1 viruses in mammals have been identified, the detailed molecular mechanism remains poorly defined and requires further clarification. 28100622 11 36 theme H5N1 2229:2232 arg1 virus 2234:2238 H5N1 virus 2229:2238 H5N1 virus 2229:2238 This glycosylation event enhanced viral productivity, exacerbated the host response, and thereby contributed to the high pathogenicity of H5N1 virus in mice. 28100622 10 37 from positions 1973:1981 arg1 glycosylation 1956:1968 glycosylation 1956:1968 glycosylation at positions 158 to 160 of the HA protein of two naturally occurring H5N1 viruses 1956:2050 In this study, we identified glycosylation at positions 158 to 160 of the HA protein of two naturally occurring H5N1 viruses as an important virulence determinant. 28100622 10 37 from positions 1973:1981 arg1 determinant 2078:2088 an important virulence determinant 2055:2088 an important virulence determinant 2055:2088 In this study, we identified glycosylation at positions 158 to 160 of the HA protein of two naturally occurring H5N1 viruses as an important virulence determinant. 28100622 4 38 from difference 743:752 arg1 virulence 757:765 virulence 757:765 virulence 757:765 In this study, we explored the molecular determinants and potential mechanism for this difference in virulence. 28100622 5 39 theme influenza 959:967 arg1 viruses 969:975 these H5N1 influenza viruses 948:975 these H5N1 influenza viruses 948:975 By using reverse genetics, we found that a single amino acid at position 158 of the hemagglutinin (HA) protein substantially affected the systemic replication and pathogenicity of these H5N1 influenza viruses in mice. 28100622 7 40 theme determinants 1327:1338 arg1 understanding 1306:1318 our understanding 1302:1318 our understanding of the determinants of pathogenicity of H5N1 viruses in mammals.IMPORTANCE Highly pathogenic avian influenza (HPAI) H5N1 viruses 1302:1447 These findings further our understanding of the determinants of pathogenicity of H5N1 viruses in mammals.IMPORTANCE Highly pathogenic avian influenza (HPAI) H5N1 viruses continue to evolve in nature and threaten human health. 28100622 9 41 theme control 1797:1803 arg1 strategies 1805:1814 more effective control strategies 1782:1814 more effective control strategies 1782:1814 A thorough understanding of the pathogenic mechanisms of these viruses will help us to develop more effective control strategies; however, such mechanisms and virulent determinants for H5N1 influenza viruses have not been fully elucidated. 28100622 8 42 theme virus 1526:1530 arg1 HA 1547:1548 HA 1547:1548 HA 1547:1548 Key mutations in the virus hemagglutinin (HA) protein or reassortment with other pandemic viruses endow HPAI H5N1 viruses with the potential for aerosol transmissibility in mammals. 28100622 8 42 theme virus 1526:1530 arg1 hemagglutinin 1532:1544 the virus hemagglutinin 1522:1544 the virus hemagglutinin (HA) protein 1522:1557 Key mutations in the virus hemagglutinin (HA) protein or reassortment with other pandemic viruses endow HPAI H5N1 viruses with the potential for aerosol transmissibility in mammals. 28100622 10 43 gly glycosylation 1956:1968 arg1 protein 2004:2010 the HA protein 1997:2010 the HA protein of two naturally occurring H5N1 viruses 1997:2050 In this study, we identified glycosylation at positions 158 to 160 of the HA protein of two naturally occurring H5N1 viruses as an important virulence determinant. 28100622 10 43 gly glycosylation 1956:1968 arg1 study 1935:1939 this study 1930:1939 this study 1930:1939 In this study, we identified glycosylation at positions 158 to 160 of the HA protein of two naturally occurring H5N1 viruses as an important virulence determinant. 28100622 10 43 gly glycosylation 1956:1968 arg2 positions 1973:1981 positions 158 to 160 1973:1992 positions 158 to 160 1973:1992 In this study, we identified glycosylation at positions 158 to 160 of the HA protein of two naturally occurring H5N1 viruses as an important virulence determinant. 28100622 10 43 gly glycosylation 1956:1968 arg1 positions 1973:1981 positions 158 to 160 1973:1992 positions 158 to 160 1973:1992 In this study, we identified glycosylation at positions 158 to 160 of the HA protein of two naturally occurring H5N1 viruses as an important virulence determinant. 28100622 2 44 theme detailed 399:406 arg1 mechanism 418:426 the detailed molecular mechanism 395:426 the detailed molecular mechanism 395:426 Although several viral determinants and host factors that influence the virulence of HPAI H5N1 viruses in mammals have been identified, the detailed molecular mechanism remains poorly defined and requires further clarification. 28100622 2 45 theme further 464:470 arg1 clarification 472:484 further clarification 464:484 further clarification 464:484 Although several viral determinants and host factors that influence the virulence of HPAI H5N1 viruses in mammals have been identified, the detailed molecular mechanism remains poorly defined and requires further clarification. 28100622 10 46 theme H5N1 2039:2042 arg1 viruses 2044:2050 two naturally occurring H5N1 viruses 2015:2050 two naturally occurring H5N1 viruses 2015:2050 In this study, we identified glycosylation at positions 158 to 160 of the HA protein of two naturally occurring H5N1 viruses as an important virulence determinant. 28100622 0 47 theme Protein 35:41 arg1 Glycosylation 0:12 Glycosylation 0:12 Glycosylation of the Hemagglutinin Protein of H5N1 Influenza Virus 0:65 Glycosylation of the Hemagglutinin Protein of H5N1 Influenza Virus Increases Its Virulence in Mice by Exacerbating the Host Immune Response. 28100622 5 48 theme reverse 777:783 arg1 genetics 785:792 reverse genetics 777:792 reverse genetics 777:792 By using reverse genetics, we found that a single amino acid at position 158 of the hemagglutinin (HA) protein substantially affected the systemic replication and pathogenicity of these H5N1 influenza viruses in mice. 28100622 6 49 gly glycosylation 1050:1062 arg2 positions 1067:1075 positions 158 to 160 1067:1086 positions 158 to 160 1067:1086 We further found that the G158N mutation introduced an N-linked glycosylation at positions 158 to 160 of the HA protein and that this N-linked glycosylation enhanced viral productivity in infected mammalian cells and induced stronger host immune and inflammatory responses to viral infection. 28100622 6 49 gly glycosylation 1050:1062 arg1 positions 1067:1075 positions 158 to 160 1067:1086 positions 158 to 160 1067:1086 We further found that the G158N mutation introduced an N-linked glycosylation at positions 158 to 160 of the HA protein and that this N-linked glycosylation enhanced viral productivity in infected mammalian cells and induced stronger host immune and inflammatory responses to viral infection. 28100622 6 49 gly glycosylation 1050:1062 arg1 protein 1098:1104 the HA protein 1091:1104 the HA protein 1091:1104 We further found that the G158N mutation introduced an N-linked glycosylation at positions 158 to 160 of the HA protein and that this N-linked glycosylation enhanced viral productivity in infected mammalian cells and induced stronger host immune and inflammatory responses to viral infection. 28100622 6 50 dep 160 1084:1086 arg1 to 1081:1082 to 1081:1082 to 1081:1082 We further found that the G158N mutation introduced an N-linked glycosylation at positions 158 to 160 of the HA protein and that this N-linked glycosylation enhanced viral productivity in infected mammalian cells and induced stronger host immune and inflammatory responses to viral infection. 28100622 0 51 theme H5N1 46:49 arg1 Virus 61:65 H5N1 Influenza Virus 46:65 H5N1 Influenza Virus 46:65 Glycosylation of the Hemagglutinin Protein of H5N1 Influenza Virus Increases Its Virulence in Mice by Exacerbating the Host Immune Response. 28100622 6 52 theme HA 1095:1096 arg1 protein 1098:1104 the HA protein 1091:1104 the HA protein 1091:1104 We further found that the G158N mutation introduced an N-linked glycosylation at positions 158 to 160 of the HA protein and that this N-linked glycosylation enhanced viral productivity in infected mammalian cells and induced stronger host immune and inflammatory responses to viral infection. 28100622 9 53 theme virulent 1846:1853 arg1 determinants 1855:1866 virulent determinants 1846:1866 virulent determinants 1846:1866 A thorough understanding of the pathogenic mechanisms of these viruses will help us to develop more effective control strategies; however, such mechanisms and virulent determinants for H5N1 influenza viruses have not been fully elucidated. 28100622 5 54 from pathogenicity 931:943 arg1 mice 980:983 mice 980:983 mice 980:983 By using reverse genetics, we found that a single amino acid at position 158 of the hemagglutinin (HA) protein substantially affected the systemic replication and pathogenicity of these H5N1 influenza viruses in mice. 28100622 10 55 theme viruses 2044:2050 arg1 protein 2004:2010 the HA protein 1997:2010 the HA protein of two naturally occurring H5N1 viruses 1997:2050 In this study, we identified glycosylation at positions 158 to 160 of the HA protein of two naturally occurring H5N1 viruses as an important virulence determinant. 28100622 8 56 theme pandemic 1586:1593 arg1 viruses 1595:1601 other pandemic viruses 1580:1601 other pandemic viruses 1580:1601 Key mutations in the virus hemagglutinin (HA) protein or reassortment with other pandemic viruses endow HPAI H5N1 viruses with the potential for aerosol transmissibility in mammals. 28100622 6 57 from positions 1067:1075 arg1 glycosylation 1050:1062 an N-linked glycosylation 1038:1062 an N-linked glycosylation at positions 158 to 160 of the HA protein 1038:1104 We further found that the G158N mutation introduced an N-linked glycosylation at positions 158 to 160 of the HA protein and that this N-linked glycosylation enhanced viral productivity in infected mammalian cells and induced stronger host immune and inflammatory responses to viral infection. 28100622 2 58 theme viruses 354:360 arg1 virulence 331:339 the virulence 327:339 the virulence of HPAI H5N1 viruses in mammals 327:371 Although several viral determinants and host factors that influence the virulence of HPAI H5N1 viruses in mammals have been identified, the detailed molecular mechanism remains poorly defined and requires further clarification. 28100622 8 59 theme aerosol 1650:1656 arg1 transmissibility 1658:1673 aerosol transmissibility 1650:1673 aerosol transmissibility in mammals 1650:1684 Key mutations in the virus hemagglutinin (HA) protein or reassortment with other pandemic viruses endow HPAI H5N1 viruses with the potential for aerosol transmissibility in mammals. 28100622 9 60 theme influenza 1877:1885 arg1 viruses 1887:1893 H5N1 influenza viruses 1872:1893 H5N1 influenza viruses 1872:1893 A thorough understanding of the pathogenic mechanisms of these viruses will help us to develop more effective control strategies; however, such mechanisms and virulent determinants for H5N1 influenza viruses have not been fully elucidated. 28100622 2 61 theme HPAI 344:347 arg1 viruses 354:360 HPAI H5N1 viruses 344:360 HPAI H5N1 viruses 344:360 Although several viral determinants and host factors that influence the virulence of HPAI H5N1 viruses in mammals have been identified, the detailed molecular mechanism remains poorly defined and requires further clarification. 28100622 10 62 theme virulence 2068:2076 arg1 glycosylation 1956:1968 glycosylation 1956:1968 glycosylation at positions 158 to 160 of the HA protein of two naturally occurring H5N1 viruses 1956:2050 In this study, we identified glycosylation at positions 158 to 160 of the HA protein of two naturally occurring H5N1 viruses as an important virulence determinant. 28100622 10 62 theme virulence 2068:2076 arg1 determinant 2078:2088 an important virulence determinant 2055:2088 an important virulence determinant 2055:2088 In this study, we identified glycosylation at positions 158 to 160 of the HA protein of two naturally occurring H5N1 viruses as an important virulence determinant. 28100622 3 63 contain had 575:577 arg2 genomes 593:599 similar viral genomes 579:599 similar viral genomes 579:599 In our previous studies, we characterized two naturally isolated HPAI H5N1 viruses that had similar viral genomes but differed substantially in their lethality in mice. 28100622 3 63 contain had 575:577 arg1 viruses 562:568 two naturally isolated HPAI H5N1 viruses 529:568 two naturally isolated HPAI H5N1 viruses that had similar viral genomes but differed substantially in their lethality in mice 529:653 In our previous studies, we characterized two naturally isolated HPAI H5N1 viruses that had similar viral genomes but differed substantially in their lethality in mice. 28100622 6 64 theme viral 1262:1266 arg1 infection 1268:1276 viral infection 1262:1276 viral infection 1262:1276 We further found that the G158N mutation introduced an N-linked glycosylation at positions 158 to 160 of the HA protein and that this N-linked glycosylation enhanced viral productivity in infected mammalian cells and induced stronger host immune and inflammatory responses to viral infection. 28100622 2 65 theme viral 276:280 arg1 determinants 282:293 several viral determinants 268:293 several viral determinants 268:293 Although several viral determinants and host factors that influence the virulence of HPAI H5N1 viruses in mammals have been identified, the detailed molecular mechanism remains poorly defined and requires further clarification. 28100622 1 66 theme public 244:249 arg1 health 251:256 public health 244:256 public health 244:256 The highly pathogenic avian influenza (HPAI) H5N1 viruses continue to circulate in nature and threaten public health. 28100622 6 67 theme N-linked 1120:1127 arg1 glycosylation 1129:1141 this N-linked glycosylation 1115:1141 this N-linked glycosylation 1115:1141 We further found that the G158N mutation introduced an N-linked glycosylation at positions 158 to 160 of the HA protein and that this N-linked glycosylation enhanced viral productivity in infected mammalian cells and induced stronger host immune and inflammatory responses to viral infection. 28100622 11 68 theme glycosylation 2096:2108 arg1 event 2110:2114 This glycosylation event 2091:2114 This glycosylation event 2091:2114 This glycosylation event enhanced viral productivity, exacerbated the host response, and thereby contributed to the high pathogenicity of H5N1 virus in mice. 28100622 2 69 from virulence 331:339 arg1 mammals 365:371 mammals 365:371 mammals 365:371 Although several viral determinants and host factors that influence the virulence of HPAI H5N1 viruses in mammals have been identified, the detailed molecular mechanism remains poorly defined and requires further clarification. 28100622 6 70 theme viral 1152:1156 arg1 productivity 1158:1169 viral productivity 1152:1169 viral productivity in infected mammalian cells 1152:1197 We further found that the G158N mutation introduced an N-linked glycosylation at positions 158 to 160 of the HA protein and that this N-linked glycosylation enhanced viral productivity in infected mammalian cells and induced stronger host immune and inflammatory responses to viral infection. 28100622 1 71 theme avian 163:167 arg1 viruses 191:197 The highly pathogenic avian influenza (HPAI) H5N1 viruses 141:197 The highly pathogenic avian influenza (HPAI) H5N1 viruses 141:197 The highly pathogenic avian influenza (HPAI) H5N1 viruses continue to circulate in nature and threaten public health. 28100622 0 72 theme Host 119:122 arg1 Response 131:138 the Host Immune Response 115:138 the Host Immune Response 115:138 Glycosylation of the Hemagglutinin Protein of H5N1 Influenza Virus Increases Its Virulence in Mice by Exacerbating the Host Immune Response. 28100622 3 73 theme HPAI 552:555 arg1 viruses 562:568 two naturally isolated HPAI H5N1 viruses 529:568 two naturally isolated HPAI H5N1 viruses that had similar viral genomes but differed substantially in their lethality in mice 529:653 In our previous studies, we characterized two naturally isolated HPAI H5N1 viruses that had similar viral genomes but differed substantially in their lethality in mice. 28100622 5 74 theme single 811:816 arg1 acid 824:827 a single amino acid 809:827 a single amino acid at position 158 of the hemagglutinin (HA) protein 809:877 By using reverse genetics, we found that a single amino acid at position 158 of the hemagglutinin (HA) protein substantially affected the systemic replication and pathogenicity of these H5N1 influenza viruses in mice. 28100622 0 75 from Virulence 81:89 arg1 Mice 94:97 Mice 94:97 Mice 94:97 Glycosylation of the Hemagglutinin Protein of H5N1 Influenza Virus Increases Its Virulence in Mice by Exacerbating the Host Immune Response. 28100622 5 76 dep replication 915:925 arg1 the 902:904 the 902:904 the 902:904 By using reverse genetics, we found that a single amino acid at position 158 of the hemagglutinin (HA) protein substantially affected the systemic replication and pathogenicity of these H5N1 influenza viruses in mice. 28100622 3 77 theme previous 494:501 arg1 studies 503:509 our previous studies 490:509 our previous studies 490:509 In our previous studies, we characterized two naturally isolated HPAI H5N1 viruses that had similar viral genomes but differed substantially in their lethality in mice. 28100622 3 78 theme viral 587:591 arg1 genomes 593:599 similar viral genomes 579:599 similar viral genomes 579:599 In our previous studies, we characterized two naturally isolated HPAI H5N1 viruses that had similar viral genomes but differed substantially in their lethality in mice. 28100622 5 79 theme protein 871:877 arg1 position 832:839 position 158 832:843 position 158 of the hemagglutinin (HA) protein 832:877 By using reverse genetics, we found that a single amino acid at position 158 of the hemagglutinin (HA) protein substantially affected the systemic replication and pathogenicity of these H5N1 influenza viruses in mice. 28100622 8 80 theme Key 1505:1507 arg1 mutations 1509:1517 Key mutations 1505:1517 Key mutations in the virus hemagglutinin (HA) protein or reassortment with other pandemic viruses 1505:1601 Key mutations in the virus hemagglutinin (HA) protein or reassortment with other pandemic viruses endow HPAI H5N1 viruses with the potential for aerosol transmissibility in mammals. 28100622 9 81 theme mechanisms 1730:1739 arg1 understanding 1698:1710 A thorough understanding 1687:1710 A thorough understanding of the pathogenic mechanisms of these viruses 1687:1756 A thorough understanding of the pathogenic mechanisms of these viruses will help us to develop more effective control strategies; however, such mechanisms and virulent determinants for H5N1 influenza viruses have not been fully elucidated. 28100622 4 82 theme molecular 687:695 arg1 determinants 697:708 the molecular determinants 683:708 the molecular determinants 683:708 In this study, we explored the molecular determinants and potential mechanism for this difference in virulence. 28100622 8 83 with viruses 1619:1625 arg1 potential 1636:1644 the potential 1632:1644 the potential for aerosol transmissibility in mammals 1632:1684 Key mutations in the virus hemagglutinin (HA) protein or reassortment with other pandemic viruses endow HPAI H5N1 viruses with the potential for aerosol transmissibility in mammals. 28100622 7 84 theme H5N1 1360:1363 arg1 viruses 1365:1371 H5N1 viruses 1360:1371 H5N1 viruses 1360:1371 These findings further our understanding of the determinants of pathogenicity of H5N1 viruses in mammals.IMPORTANCE Highly pathogenic avian influenza (HPAI) H5N1 viruses continue to evolve in nature and threaten human health. 28100622 10 85 theme HA 2001:2002 arg1 protein 2004:2010 the HA protein 1997:2010 the HA protein of two naturally occurring H5N1 viruses 1997:2050 In this study, we identified glycosylation at positions 158 to 160 of the HA protein of two naturally occurring H5N1 viruses as an important virulence determinant. 28100622 7 86 from viruses 1441:1447 arg1 determinants 1327:1338 the determinants 1323:1338 the determinants of pathogenicity of H5N1 viruses in mammals.IMPORTANCE Highly pathogenic avian influenza (HPAI) H5N1 viruses 1323:1447 These findings further our understanding of the determinants of pathogenicity of H5N1 viruses in mammals.IMPORTANCE Highly pathogenic avian influenza (HPAI) H5N1 viruses continue to evolve in nature and threaten human health. 28100622 8 87 with reassortment 1562:1573 arg1 viruses 1595:1601 other pandemic viruses 1580:1601 other pandemic viruses 1580:1601 Key mutations in the virus hemagglutinin (HA) protein or reassortment with other pandemic viruses endow HPAI H5N1 viruses with the potential for aerosol transmissibility in mammals. 28100622 5 88 theme hemagglutinin 852:864 arg1 protein 871:877 the hemagglutinin (HA) protein 848:877 the hemagglutinin (HA) protein 848:877 By using reverse genetics, we found that a single amino acid at position 158 of the hemagglutinin (HA) protein substantially affected the systemic replication and pathogenicity of these H5N1 influenza viruses in mice. 28100622 7 89 theme pathogenicity 1343:1355 arg1 determinants 1327:1338 the determinants 1323:1338 the determinants of pathogenicity of H5N1 viruses in mammals.IMPORTANCE Highly pathogenic avian influenza (HPAI) H5N1 viruses 1323:1447 These findings further our understanding of the determinants of pathogenicity of H5N1 viruses in mammals.IMPORTANCE Highly pathogenic avian influenza (HPAI) H5N1 viruses continue to evolve in nature and threaten human health. 28100622 5 90 theme HA 867:868 arg1 protein 871:877 the hemagglutinin (HA) protein 848:877 the hemagglutinin (HA) protein 848:877 By using reverse genetics, we found that a single amino acid at position 158 of the hemagglutinin (HA) protein substantially affected the systemic replication and pathogenicity of these H5N1 influenza viruses in mice. 28100622 11 91 theme high 2207:2210 arg1 pathogenicity 2212:2224 the high pathogenicity 2203:2224 the high pathogenicity of H5N1 virus in mice 2203:2246 This glycosylation event enhanced viral productivity, exacerbated the host response, and thereby contributed to the high pathogenicity of H5N1 virus in mice. 28100622 10 92 dep 160 1990:1992 arg1 to 1987:1988 to 1987:1988 to 1987:1988 In this study, we identified glycosylation at positions 158 to 160 of the HA protein of two naturally occurring H5N1 viruses as an important virulence determinant. 28100622 6 93 dep stronger 1211:1218 arg1 responses 1249:1257 host immune and inflammatory responses 1220:1257 stronger host immune and inflammatory responses to viral infection 1211:1276 We further found that the G158N mutation introduced an N-linked glycosylation at positions 158 to 160 of the HA protein and that this N-linked glycosylation enhanced viral productivity in infected mammalian cells and induced stronger host immune and inflammatory responses to viral infection. 28100622 7 94 theme avian 1413:1417 arg1 viruses 1441:1447 mammals.IMPORTANCE Highly pathogenic avian influenza (HPAI) H5N1 viruses 1376:1447 mammals.IMPORTANCE Highly pathogenic avian influenza (HPAI) H5N1 viruses 1376:1447 These findings further our understanding of the determinants of pathogenicity of H5N1 viruses in mammals.IMPORTANCE Highly pathogenic avian influenza (HPAI) H5N1 viruses continue to evolve in nature and threaten human health. 28100622 1 95 theme H5N1 186:189 arg1 viruses 191:197 The highly pathogenic avian influenza (HPAI) H5N1 viruses 141:197 The highly pathogenic avian influenza (HPAI) H5N1 viruses 141:197 The highly pathogenic avian influenza (HPAI) H5N1 viruses continue to circulate in nature and threaten public health. 28100622 5 96 theme H5N1 954:957 arg1 viruses 969:975 these H5N1 influenza viruses 948:975 these H5N1 influenza viruses 948:975 By using reverse genetics, we found that a single amino acid at position 158 of the hemagglutinin (HA) protein substantially affected the systemic replication and pathogenicity of these H5N1 influenza viruses in mice. 28100622 7 97 from pathogenicity 1343:1355 arg1 viruses 1441:1447 mammals.IMPORTANCE Highly pathogenic avian influenza (HPAI) H5N1 viruses 1376:1447 mammals.IMPORTANCE Highly pathogenic avian influenza (HPAI) H5N1 viruses 1376:1447 These findings further our understanding of the determinants of pathogenicity of H5N1 viruses in mammals.IMPORTANCE Highly pathogenic avian influenza (HPAI) H5N1 viruses continue to evolve in nature and threaten human health. 28100622 9 98 theme effective 1787:1795 arg1 strategies 1805:1814 more effective control strategies 1782:1814 more effective control strategies 1782:1814 A thorough understanding of the pathogenic mechanisms of these viruses will help us to develop more effective control strategies; however, such mechanisms and virulent determinants for H5N1 influenza viruses have not been fully elucidated. 28100622 8 99 theme hemagglutinin 1532:1544 arg1 protein 1551:1557 the virus hemagglutinin (HA) protein 1522:1557 the virus hemagglutinin (HA) protein 1522:1557 Key mutations in the virus hemagglutinin (HA) protein or reassortment with other pandemic viruses endow HPAI H5N1 viruses with the potential for aerosol transmissibility in mammals. 28100622 6 100 from productivity 1158:1169 arg1 cells 1193:1197 infected mammalian cells 1174:1197 infected mammalian cells 1174:1197 We further found that the G158N mutation introduced an N-linked glycosylation at positions 158 to 160 of the HA protein and that this N-linked glycosylation enhanced viral productivity in infected mammalian cells and induced stronger host immune and inflammatory responses to viral infection. 28100622 8 101 from mutations 1509:1517 arg1 reassortment 1562:1573 reassortment 1562:1573 reassortment 1562:1573 Key mutations in the virus hemagglutinin (HA) protein or reassortment with other pandemic viruses endow HPAI H5N1 viruses with the potential for aerosol transmissibility in mammals. 28100622 8 101 from mutations 1509:1517 arg1 protein 1551:1557 the virus hemagglutinin (HA) protein 1522:1557 the virus hemagglutinin (HA) protein 1522:1557 Key mutations in the virus hemagglutinin (HA) protein or reassortment with other pandemic viruses endow HPAI H5N1 viruses with the potential for aerosol transmissibility in mammals. 28100622 8 102 with protein 1551:1557 arg1 viruses 1595:1601 other pandemic viruses 1580:1601 other pandemic viruses 1580:1601 Key mutations in the virus hemagglutinin (HA) protein or reassortment with other pandemic viruses endow HPAI H5N1 viruses with the potential for aerosol transmissibility in mammals. 28100622 5 103 theme systemic 906:913 arg1 replication 915:925 systemic replication 906:925 systemic replication 906:925 By using reverse genetics, we found that a single amino acid at position 158 of the hemagglutinin (HA) protein substantially affected the systemic replication and pathogenicity of these H5N1 influenza viruses in mice. 28100622 6 104 theme N-linked 1041:1048 arg1 glycosylation 1050:1062 an N-linked glycosylation 1038:1062 an N-linked glycosylation at positions 158 to 160 of the HA protein 1038:1104 We further found that the G158N mutation introduced an N-linked glycosylation at positions 158 to 160 of the HA protein and that this N-linked glycosylation enhanced viral productivity in infected mammalian cells and induced stronger host immune and inflammatory responses to viral infection. 28100622 0 105 theme Hemagglutinin 21:33 arg1 Protein 35:41 the Hemagglutinin Protein 17:41 the Hemagglutinin Protein of H5N1 Influenza Virus 17:65 Glycosylation of the Hemagglutinin Protein of H5N1 Influenza Virus Increases Its Virulence in Mice by Exacerbating the Host Immune Response. 28100622 7 106 theme mammals.IMPORTANCE 1376:1393 arg1 viruses 1441:1447 mammals.IMPORTANCE Highly pathogenic avian influenza (HPAI) H5N1 viruses 1376:1447 mammals.IMPORTANCE Highly pathogenic avian influenza (HPAI) H5N1 viruses 1376:1447 These findings further our understanding of the determinants of pathogenicity of H5N1 viruses in mammals.IMPORTANCE Highly pathogenic avian influenza (HPAI) H5N1 viruses continue to evolve in nature and threaten human health. 28100622 2 107 theme molecular 408:416 arg1 mechanism 418:426 the detailed molecular mechanism 395:426 the detailed molecular mechanism 395:426 Although several viral determinants and host factors that influence the virulence of HPAI H5N1 viruses in mammals have been identified, the detailed molecular mechanism remains poorly defined and requires further clarification. 28100622 0 108 gly Glycosylation 0:12 arg1 Protein 35:41 the Hemagglutinin Protein 17:41 the Hemagglutinin Protein of H5N1 Influenza Virus 17:65 Glycosylation of the Hemagglutinin Protein of H5N1 Influenza Virus Increases Its Virulence in Mice by Exacerbating the Host Immune Response. 28100622 5 109 from replication 915:925 arg1 mice 980:983 mice 980:983 mice 980:983 By using reverse genetics, we found that a single amino acid at position 158 of the hemagglutinin (HA) protein substantially affected the systemic replication and pathogenicity of these H5N1 influenza viruses in mice. 28100622 6 110 theme G158N 1012:1016 arg1 mutation 1018:1025 the G158N mutation 1008:1025 the G158N mutation 1008:1025 We further found that the G158N mutation introduced an N-linked glycosylation at positions 158 to 160 of the HA protein and that this N-linked glycosylation enhanced viral productivity in infected mammalian cells and induced stronger host immune and inflammatory responses to viral infection. 28100622 9 111 theme such 1826:1829 arg1 mechanisms 1831:1840 such mechanisms 1826:1840 such mechanisms 1826:1840 A thorough understanding of the pathogenic mechanisms of these viruses will help us to develop more effective control strategies; however, such mechanisms and virulent determinants for H5N1 influenza viruses have not been fully elucidated. 28100622 11 112 theme virus 2234:2238 arg1 pathogenicity 2212:2224 the high pathogenicity 2203:2224 the high pathogenicity of H5N1 virus in mice 2203:2246 This glycosylation event enhanced viral productivity, exacerbated the host response, and thereby contributed to the high pathogenicity of H5N1 virus in mice. 28100622 0 113 theme Influenza 51:59 arg1 Virus 61:65 H5N1 Influenza Virus 46:65 H5N1 Influenza Virus 46:65 Glycosylation of the Hemagglutinin Protein of H5N1 Influenza Virus Increases Its Virulence in Mice by Exacerbating the Host Immune Response. 28100622 6 114 theme protein 1098:1104 arg1 glycosylation 1050:1062 an N-linked glycosylation 1038:1062 an N-linked glycosylation at positions 158 to 160 of the HA protein 1038:1104 We further found that the G158N mutation introduced an N-linked glycosylation at positions 158 to 160 of the HA protein and that this N-linked glycosylation enhanced viral productivity in infected mammalian cells and induced stronger host immune and inflammatory responses to viral infection. 28100622 8 115 theme other 1580:1584 arg1 viruses 1595:1601 other pandemic viruses 1580:1601 other pandemic viruses 1580:1601 Key mutations in the virus hemagglutinin (HA) protein or reassortment with other pandemic viruses endow HPAI H5N1 viruses with the potential for aerosol transmissibility in mammals. 28100622 8 116 theme H5N1 1614:1617 arg1 viruses 1619:1625 HPAI H5N1 viruses 1609:1625 HPAI H5N1 viruses with the potential for aerosol transmissibility in mammals 1609:1684 Key mutations in the virus hemagglutinin (HA) protein or reassortment with other pandemic viruses endow HPAI H5N1 viruses with the potential for aerosol transmissibility in mammals. 28100622 5 117 theme viruses 969:975 arg1 pathogenicity 931:943 pathogenicity 931:943 pathogenicity 931:943 By using reverse genetics, we found that a single amino acid at position 158 of the hemagglutinin (HA) protein substantially affected the systemic replication and pathogenicity of these H5N1 influenza viruses in mice. 28100622 5 117 theme viruses 969:975 arg1 replication 915:925 systemic replication 906:925 systemic replication 906:925 By using reverse genetics, we found that a single amino acid at position 158 of the hemagglutinin (HA) protein substantially affected the systemic replication and pathogenicity of these H5N1 influenza viruses in mice. 28100622 11 118 from pathogenicity 2212:2224 arg1 mice 2243:2246 mice 2243:2246 mice 2243:2246 This glycosylation event enhanced viral productivity, exacerbated the host response, and thereby contributed to the high pathogenicity of H5N1 virus in mice. 28100622 9 119 theme H5N1 1872:1875 arg1 viruses 1887:1893 H5N1 influenza viruses 1872:1893 H5N1 influenza viruses 1872:1893 A thorough understanding of the pathogenic mechanisms of these viruses will help us to develop more effective control strategies; however, such mechanisms and virulent determinants for H5N1 influenza viruses have not been fully elucidated. 28100622 8 120 theme HPAI 1609:1612 arg1 viruses 1619:1625 HPAI H5N1 viruses 1609:1625 HPAI H5N1 viruses with the potential for aerosol transmissibility in mammals 1609:1684 Key mutations in the virus hemagglutinin (HA) protein or reassortment with other pandemic viruses endow HPAI H5N1 viruses with the potential for aerosol transmissibility in mammals. 28100622 6 121 link N-linked 1041:1048 arg1 glycosylation 1050:1062 an N-linked glycosylation 1038:1062 an N-linked glycosylation at positions 158 to 160 of the HA protein 1038:1104 We further found that the G158N mutation introduced an N-linked glycosylation at positions 158 to 160 of the HA protein and that this N-linked glycosylation enhanced viral productivity in infected mammalian cells and induced stronger host immune and inflammatory responses to viral infection. 28100622 2 122 theme H5N1 349:352 arg1 viruses 354:360 HPAI H5N1 viruses 344:360 HPAI H5N1 viruses 344:360 Although several viral determinants and host factors that influence the virulence of HPAI H5N1 viruses in mammals have been identified, the detailed molecular mechanism remains poorly defined and requires further clarification. 27694802 5 0 theme cell-cycle 935:944 arg1 arrest 946:951 cell-cycle arrest 935:951 cell-cycle arrest accompanied by induction of p21, autofluorescence, and cell morphology changes, all hallmarks of senescence 935:1059 In these cell lines, OST inhibition causes cell-cycle arrest accompanied by induction of p21, autofluorescence, and cell morphology changes, all hallmarks of senescence. 27694802 1 1 link -linked 97:103 arg1 modification 132:143 a protein modification 122:143 a protein modification critical for glycoprotein folding, stability, and cellular localization 122:215 Asparagine (N)-linked glycosylation is a protein modification critical for glycoprotein folding, stability, and cellular localization. 27694802 1 1 link -linked 97:103 arg1 glycosylation 105:117 Asparagine (N)-linked glycosylation 83:117 Asparagine (N)-linked glycosylation 83:117 Asparagine (N)-linked glycosylation is a protein modification critical for glycoprotein folding, stability, and cellular localization. 27694802 6 2 dep potential 1105:1113 arg1 therapeutic 1115:1125 therapeutic 1115:1125 therapeutic 1115:1125 These results identify OST inhibition as a potential therapeutic approach for treating receptor-tyrosine-kinase-dependent tumors and provides a chemical probe for reversibly regulating N-linked glycosylation in mammalian cells. 27694802 6 3 theme N-linked 1247:1254 arg1 glycosylation 1256:1268 N-linked glycosylation 1247:1268 N-linked glycosylation in mammalian cells 1247:1287 These results identify OST inhibition as a potential therapeutic approach for treating receptor-tyrosine-kinase-dependent tumors and provides a chemical probe for reversibly regulating N-linked glycosylation in mammalian cells. 27694802 6 4 theme mammalian 1273:1281 arg1 cells 1283:1287 mammalian cells 1273:1287 mammalian cells 1273:1287 These results identify OST inhibition as a potential therapeutic approach for treating receptor-tyrosine-kinase-dependent tumors and provides a chemical probe for reversibly regulating N-linked glycosylation in mammalian cells. 27694802 6 5 theme OST 1085:1087 arg1 inhibition 1089:1098 OST inhibition 1085:1098 OST inhibition 1085:1098 These results identify OST inhibition as a potential therapeutic approach for treating receptor-tyrosine-kinase-dependent tumors and provides a chemical probe for reversibly regulating N-linked glycosylation in mammalian cells. 27694802 6 5 theme OST 1085:1087 arg1 approach 1127:1134 a potential therapeutic approach 1103:1134 a potential therapeutic approach for treating receptor-tyrosine-kinase-dependent tumors and provides a chemical probe for reversibly regulating N-linked glycosylation in mammalian cells 1103:1287 These results identify OST inhibition as a potential therapeutic approach for treating receptor-tyrosine-kinase-dependent tumors and provides a chemical probe for reversibly regulating N-linked glycosylation in mammalian cells. 27694802 5 6 theme p21 981:983 arg1 induction 968:976 induction 968:976 induction of p21, autofluorescence, and cell morphology changes, all hallmarks of senescence 968:1059 In these cell lines, OST inhibition causes cell-cycle arrest accompanied by induction of p21, autofluorescence, and cell morphology changes, all hallmarks of senescence. 27694802 4 7 gly glycoprotein 738:749 arg1 glycoprotein 738:749 the epidermal growth factor receptor (EGFR) glycoprotein 694:749 the epidermal growth factor receptor (EGFR) glycoprotein 694:749 In non-small-cell lung cancer cells, NGI-1 blocks cell-surface localization and signaling of the epidermal growth factor receptor (EGFR) glycoprotein, but selectively arrests proliferation in only those cell lines that are dependent on EGFR (or fibroblast growth factor, FGFR) for survival. 27694802 5 8 theme cell 1008:1011 arg1 changes 1024:1030 cell morphology changes 1008:1030 cell morphology changes 1008:1030 In these cell lines, OST inhibition causes cell-cycle arrest accompanied by induction of p21, autofluorescence, and cell morphology changes, all hallmarks of senescence. 27694802 6 9 from glycosylation 1256:1268 arg1 cells 1283:1287 mammalian cells 1273:1287 mammalian cells 1273:1287 These results identify OST inhibition as a potential therapeutic approach for treating receptor-tyrosine-kinase-dependent tumors and provides a chemical probe for reversibly regulating N-linked glycosylation in mammalian cells. 27694802 3 10 theme multiple 529:536 arg1 isoforms 538:545 multiple isoforms 529:545 multiple isoforms 529:545 NGI-1 targets oligosaccharyltransferase (OST), a hetero-oligomeric enzyme that exists in multiple isoforms and transfers oligosaccharides to recipient proteins. 27694802 4 11 theme cell 804:807 arg1 lines 809:813 only those cell lines 793:813 only those cell lines that are dependent on EGFR (or fibroblast growth factor, FGFR) for survival 793:889 In non-small-cell lung cancer cells, NGI-1 blocks cell-surface localization and signaling of the epidermal growth factor receptor (EGFR) glycoprotein, but selectively arrests proliferation in only those cell lines that are dependent on EGFR (or fibroblast growth factor, FGFR) for survival. 27694802 5 12 theme morphology 1013:1022 arg1 changes 1024:1030 cell morphology changes 1008:1030 cell morphology changes 1008:1030 In these cell lines, OST inhibition causes cell-cycle arrest accompanied by induction of p21, autofluorescence, and cell morphology changes, all hallmarks of senescence. 27694802 6 13 theme potential 1105:1113 arg1 inhibition 1089:1098 OST inhibition 1085:1098 OST inhibition 1085:1098 These results identify OST inhibition as a potential therapeutic approach for treating receptor-tyrosine-kinase-dependent tumors and provides a chemical probe for reversibly regulating N-linked glycosylation in mammalian cells. 27694802 6 13 theme potential 1105:1113 arg1 approach 1127:1134 a potential therapeutic approach 1103:1134 a potential therapeutic approach for treating receptor-tyrosine-kinase-dependent tumors and provides a chemical probe for reversibly regulating N-linked glycosylation in mammalian cells 1103:1287 These results identify OST inhibition as a potential therapeutic approach for treating receptor-tyrosine-kinase-dependent tumors and provides a chemical probe for reversibly regulating N-linked glycosylation in mammalian cells. 27694802 5 14 theme cell 901:904 arg1 lines 906:910 these cell lines 895:910 these cell lines 895:910 In these cell lines, OST inhibition causes cell-cycle arrest accompanied by induction of p21, autofluorescence, and cell morphology changes, all hallmarks of senescence. 27694802 4 15 theme cell-surface 651:662 arg1 localization 664:675 cell-surface localization 651:675 cell-surface localization 651:675 In non-small-cell lung cancer cells, NGI-1 blocks cell-surface localization and signaling of the epidermal growth factor receptor (EGFR) glycoprotein, but selectively arrests proliferation in only those cell lines that are dependent on EGFR (or fibroblast growth factor, FGFR) for survival. 27694802 2 16 theme biosynthetic 279:290 arg1 pathway 292:298 this biosynthetic pathway 274:298 this biosynthetic pathway 274:298 To identify small molecules that inhibit new targets in this biosynthetic pathway, we initiated a cell-based high-throughput screen and lead-compound-optimization campaign that delivered a cell-permeable inhibitor, NGI-1. 27694802 2 17 theme high-throughput 327:341 arg1 screen 343:348 a cell-based high-throughput screen 314:348 a cell-based high-throughput screen 314:348 To identify small molecules that inhibit new targets in this biosynthetic pathway, we initiated a cell-based high-throughput screen and lead-compound-optimization campaign that delivered a cell-permeable inhibitor, NGI-1. 27694802 4 18 dep EGFR 837:840 arg1 FGFR 872:875 FGFR 872:875 FGFR 872:875 In non-small-cell lung cancer cells, NGI-1 blocks cell-surface localization and signaling of the epidermal growth factor receptor (EGFR) glycoprotein, but selectively arrests proliferation in only those cell lines that are dependent on EGFR (or fibroblast growth factor, FGFR) for survival. 27694802 4 18 dep EGFR 837:840 arg1 factor 864:869 fibroblast growth factor 846:869 fibroblast growth factor 846:869 In non-small-cell lung cancer cells, NGI-1 blocks cell-surface localization and signaling of the epidermal growth factor receptor (EGFR) glycoprotein, but selectively arrests proliferation in only those cell lines that are dependent on EGFR (or fibroblast growth factor, FGFR) for survival. 27694802 4 19 theme glycoprotein 738:749 arg1 signaling 681:689 signaling 681:689 signaling 681:689 In non-small-cell lung cancer cells, NGI-1 blocks cell-surface localization and signaling of the epidermal growth factor receptor (EGFR) glycoprotein, but selectively arrests proliferation in only those cell lines that are dependent on EGFR (or fibroblast growth factor, FGFR) for survival. 27694802 4 19 theme glycoprotein 738:749 arg1 localization 664:675 cell-surface localization 651:675 cell-surface localization 651:675 In non-small-cell lung cancer cells, NGI-1 blocks cell-surface localization and signaling of the epidermal growth factor receptor (EGFR) glycoprotein, but selectively arrests proliferation in only those cell lines that are dependent on EGFR (or fibroblast growth factor, FGFR) for survival. 27694802 0 20 theme Oligosaccharyltransferase 0:24 arg1 inhibition 26:35 Oligosaccharyltransferase inhibition 0:35 Oligosaccharyltransferase inhibition 0:35 Oligosaccharyltransferase inhibition induces senescence in RTK-driven tumor cells. 27694802 4 21 theme cancer 624:629 arg1 cells 631:635 non-small-cell lung cancer cells 604:635 non-small-cell lung cancer cells 604:635 In non-small-cell lung cancer cells, NGI-1 blocks cell-surface localization and signaling of the epidermal growth factor receptor (EGFR) glycoprotein, but selectively arrests proliferation in only those cell lines that are dependent on EGFR (or fibroblast growth factor, FGFR) for survival. 27694802 2 22 theme cell-based 316:325 arg1 screen 343:348 a cell-based high-throughput screen 314:348 a cell-based high-throughput screen 314:348 To identify small molecules that inhibit new targets in this biosynthetic pathway, we initiated a cell-based high-throughput screen and lead-compound-optimization campaign that delivered a cell-permeable inhibitor, NGI-1. 27694802 6 23 gly glycosylation 1256:1268 arg1 cells 1283:1287 mammalian cells 1273:1287 mammalian cells 1273:1287 These results identify OST inhibition as a potential therapeutic approach for treating receptor-tyrosine-kinase-dependent tumors and provides a chemical probe for reversibly regulating N-linked glycosylation in mammalian cells. 27694802 1 24 theme cellular 195:202 arg1 localization 204:215 cellular localization 195:215 cellular localization 195:215 Asparagine (N)-linked glycosylation is a protein modification critical for glycoprotein folding, stability, and cellular localization. 27694802 4 25 theme lung 619:622 arg1 cells 631:635 non-small-cell lung cancer cells 604:635 non-small-cell lung cancer cells 604:635 In non-small-cell lung cancer cells, NGI-1 blocks cell-surface localization and signaling of the epidermal growth factor receptor (EGFR) glycoprotein, but selectively arrests proliferation in only those cell lines that are dependent on EGFR (or fibroblast growth factor, FGFR) for survival. 27694802 2 26 theme small 230:234 arg1 molecules 236:244 small molecules 230:244 small molecules that inhibit new targets in this biosynthetic pathway 230:298 To identify small molecules that inhibit new targets in this biosynthetic pathway, we initiated a cell-based high-throughput screen and lead-compound-optimization campaign that delivered a cell-permeable inhibitor, NGI-1. 27694802 5 27 theme autofluorescence 986:1001 arg1 induction 968:976 induction 968:976 induction of p21, autofluorescence, and cell morphology changes, all hallmarks of senescence 968:1059 In these cell lines, OST inhibition causes cell-cycle arrest accompanied by induction of p21, autofluorescence, and cell morphology changes, all hallmarks of senescence. 27694802 4 28 theme growth 708:713 arg1 EGFR 732:735 EGFR 732:735 EGFR 732:735 In non-small-cell lung cancer cells, NGI-1 blocks cell-surface localization and signaling of the epidermal growth factor receptor (EGFR) glycoprotein, but selectively arrests proliferation in only those cell lines that are dependent on EGFR (or fibroblast growth factor, FGFR) for survival. 27694802 4 28 theme growth 708:713 arg1 receptor 722:729 the epidermal growth factor receptor 694:729 the epidermal growth factor receptor (EGFR) glycoprotein 694:749 In non-small-cell lung cancer cells, NGI-1 blocks cell-surface localization and signaling of the epidermal growth factor receptor (EGFR) glycoprotein, but selectively arrests proliferation in only those cell lines that are dependent on EGFR (or fibroblast growth factor, FGFR) for survival. 27694802 1 29 theme -linked 97:103 arg1 modification 132:143 a protein modification 122:143 a protein modification critical for glycoprotein folding, stability, and cellular localization 122:215 Asparagine (N)-linked glycosylation is a protein modification critical for glycoprotein folding, stability, and cellular localization. 27694802 1 29 theme -linked 97:103 arg1 glycosylation 105:117 Asparagine (N)-linked glycosylation 83:117 Asparagine (N)-linked glycosylation 83:117 Asparagine (N)-linked glycosylation is a protein modification critical for glycoprotein folding, stability, and cellular localization. 27694802 4 30 theme epidermal 698:706 arg1 EGFR 732:735 EGFR 732:735 EGFR 732:735 In non-small-cell lung cancer cells, NGI-1 blocks cell-surface localization and signaling of the epidermal growth factor receptor (EGFR) glycoprotein, but selectively arrests proliferation in only those cell lines that are dependent on EGFR (or fibroblast growth factor, FGFR) for survival. 27694802 4 30 theme epidermal 698:706 arg1 receptor 722:729 the epidermal growth factor receptor 694:729 the epidermal growth factor receptor (EGFR) glycoprotein 694:749 In non-small-cell lung cancer cells, NGI-1 blocks cell-surface localization and signaling of the epidermal growth factor receptor (EGFR) glycoprotein, but selectively arrests proliferation in only those cell lines that are dependent on EGFR (or fibroblast growth factor, FGFR) for survival. 27694802 0 31 theme RTK-driven 59:68 arg1 cells 76:80 RTK-driven tumor cells 59:80 RTK-driven tumor cells 59:80 Oligosaccharyltransferase inhibition induces senescence in RTK-driven tumor cells. 27694802 2 32 theme lead-compound-optimization 354:379 arg1 campaign 381:388 lead-compound-optimization campaign 354:388 lead-compound-optimization campaign 354:388 To identify small molecules that inhibit new targets in this biosynthetic pathway, we initiated a cell-based high-throughput screen and lead-compound-optimization campaign that delivered a cell-permeable inhibitor, NGI-1. 27694802 4 33 theme receptor 722:729 arg1 glycoprotein 738:749 the epidermal growth factor receptor (EGFR) glycoprotein 694:749 the epidermal growth factor receptor (EGFR) glycoprotein 694:749 In non-small-cell lung cancer cells, NGI-1 blocks cell-surface localization and signaling of the epidermal growth factor receptor (EGFR) glycoprotein, but selectively arrests proliferation in only those cell lines that are dependent on EGFR (or fibroblast growth factor, FGFR) for survival. 27694802 5 34 theme senescence 1050:1059 arg1 hallmarks 1037:1045 all hallmarks 1033:1045 all hallmarks of senescence 1033:1059 In these cell lines, OST inhibition causes cell-cycle arrest accompanied by induction of p21, autofluorescence, and cell morphology changes, all hallmarks of senescence. 27694802 5 34 theme senescence 1050:1059 arg1 p21 981:983 p21 981:983 p21 981:983 In these cell lines, OST inhibition causes cell-cycle arrest accompanied by induction of p21, autofluorescence, and cell morphology changes, all hallmarks of senescence. 27694802 5 35 theme OST 913:915 arg1 inhibition 917:926 OST inhibition 913:926 OST inhibition 913:926 In these cell lines, OST inhibition causes cell-cycle arrest accompanied by induction of p21, autofluorescence, and cell morphology changes, all hallmarks of senescence. 27694802 3 36 theme hetero-oligomeric 489:505 arg1 enzyme 507:512 a hetero-oligomeric enzyme 487:512 a hetero-oligomeric enzyme that exists in multiple isoforms and transfers oligosaccharides to recipient proteins 487:598 NGI-1 targets oligosaccharyltransferase (OST), a hetero-oligomeric enzyme that exists in multiple isoforms and transfers oligosaccharides to recipient proteins. 27694802 3 36 theme hetero-oligomeric 489:505 arg1 oligosaccharyltransferase 454:478 oligosaccharyltransferase 454:478 oligosaccharyltransferase (OST) 454:484 NGI-1 targets oligosaccharyltransferase (OST), a hetero-oligomeric enzyme that exists in multiple isoforms and transfers oligosaccharides to recipient proteins. 27694802 4 37 theme factor 715:720 arg1 EGFR 732:735 EGFR 732:735 EGFR 732:735 In non-small-cell lung cancer cells, NGI-1 blocks cell-surface localization and signaling of the epidermal growth factor receptor (EGFR) glycoprotein, but selectively arrests proliferation in only those cell lines that are dependent on EGFR (or fibroblast growth factor, FGFR) for survival. 27694802 4 37 theme factor 715:720 arg1 receptor 722:729 the epidermal growth factor receptor 694:729 the epidermal growth factor receptor (EGFR) glycoprotein 694:749 In non-small-cell lung cancer cells, NGI-1 blocks cell-surface localization and signaling of the epidermal growth factor receptor (EGFR) glycoprotein, but selectively arrests proliferation in only those cell lines that are dependent on EGFR (or fibroblast growth factor, FGFR) for survival. 27694802 1 38 gly glycoprotein 158:169 arg1 glycoprotein 158:169 glycoprotein folding 158:177 glycoprotein folding 158:177 Asparagine (N)-linked glycosylation is a protein modification critical for glycoprotein folding, stability, and cellular localization. 27694802 6 39 theme chemical 1206:1213 arg1 probe 1215:1219 a chemical probe 1204:1219 a chemical probe for reversibly regulating N-linked glycosylation in mammalian cells 1204:1287 These results identify OST inhibition as a potential therapeutic approach for treating receptor-tyrosine-kinase-dependent tumors and provides a chemical probe for reversibly regulating N-linked glycosylation in mammalian cells. 27694802 0 40 theme tumor 70:74 arg1 cells 76:80 RTK-driven tumor cells 59:80 RTK-driven tumor cells 59:80 Oligosaccharyltransferase inhibition induces senescence in RTK-driven tumor cells. 27694802 4 41 theme non-small-cell 604:617 arg1 cells 631:635 non-small-cell lung cancer cells 604:635 non-small-cell lung cancer cells 604:635 In non-small-cell lung cancer cells, NGI-1 blocks cell-surface localization and signaling of the epidermal growth factor receptor (EGFR) glycoprotein, but selectively arrests proliferation in only those cell lines that are dependent on EGFR (or fibroblast growth factor, FGFR) for survival. 27694802 1 42 theme glycoprotein 158:169 arg1 folding 171:177 glycoprotein folding 158:177 glycoprotein folding 158:177 Asparagine (N)-linked glycosylation is a protein modification critical for glycoprotein folding, stability, and cellular localization. 27694802 1 43 theme protein 124:130 arg1 modification 132:143 a protein modification 122:143 a protein modification critical for glycoprotein folding, stability, and cellular localization 122:215 Asparagine (N)-linked glycosylation is a protein modification critical for glycoprotein folding, stability, and cellular localization. 27694802 1 43 theme protein 124:130 arg1 glycosylation 105:117 Asparagine (N)-linked glycosylation 83:117 Asparagine (N)-linked glycosylation 83:117 Asparagine (N)-linked glycosylation is a protein modification critical for glycoprotein folding, stability, and cellular localization. 27694802 4 44 theme growth 857:862 arg1 FGFR 872:875 FGFR 872:875 FGFR 872:875 In non-small-cell lung cancer cells, NGI-1 blocks cell-surface localization and signaling of the epidermal growth factor receptor (EGFR) glycoprotein, but selectively arrests proliferation in only those cell lines that are dependent on EGFR (or fibroblast growth factor, FGFR) for survival. 27694802 4 44 theme growth 857:862 arg1 factor 864:869 fibroblast growth factor 846:869 fibroblast growth factor 846:869 In non-small-cell lung cancer cells, NGI-1 blocks cell-surface localization and signaling of the epidermal growth factor receptor (EGFR) glycoprotein, but selectively arrests proliferation in only those cell lines that are dependent on EGFR (or fibroblast growth factor, FGFR) for survival. 27694802 4 45 theme fibroblast 846:855 arg1 FGFR 872:875 FGFR 872:875 FGFR 872:875 In non-small-cell lung cancer cells, NGI-1 blocks cell-surface localization and signaling of the epidermal growth factor receptor (EGFR) glycoprotein, but selectively arrests proliferation in only those cell lines that are dependent on EGFR (or fibroblast growth factor, FGFR) for survival. 27694802 4 45 theme fibroblast 846:855 arg1 factor 864:869 fibroblast growth factor 846:869 fibroblast growth factor 846:869 In non-small-cell lung cancer cells, NGI-1 blocks cell-surface localization and signaling of the epidermal growth factor receptor (EGFR) glycoprotein, but selectively arrests proliferation in only those cell lines that are dependent on EGFR (or fibroblast growth factor, FGFR) for survival. 27694802 5 46 theme changes 1024:1030 arg1 induction 968:976 induction 968:976 induction of p21, autofluorescence, and cell morphology changes, all hallmarks of senescence 968:1059 In these cell lines, OST inhibition causes cell-cycle arrest accompanied by induction of p21, autofluorescence, and cell morphology changes, all hallmarks of senescence. 27694802 1 47 theme critical 145:152 arg1 modification 132:143 a protein modification 122:143 a protein modification critical for glycoprotein folding, stability, and cellular localization 122:215 Asparagine (N)-linked glycosylation is a protein modification critical for glycoprotein folding, stability, and cellular localization. 27694802 1 47 theme critical 145:152 arg1 glycosylation 105:117 Asparagine (N)-linked glycosylation 83:117 Asparagine (N)-linked glycosylation 83:117 Asparagine (N)-linked glycosylation is a protein modification critical for glycoprotein folding, stability, and cellular localization. 27694802 6 48 link N-linked 1247:1254 arg1 glycosylation 1256:1268 N-linked glycosylation 1247:1268 N-linked glycosylation in mammalian cells 1247:1287 These results identify OST inhibition as a potential therapeutic approach for treating receptor-tyrosine-kinase-dependent tumors and provides a chemical probe for reversibly regulating N-linked glycosylation in mammalian cells. 27694802 6 49 theme receptor-tyrosine-kinase-dependent 1149:1182 arg1 tumors 1184:1189 receptor-tyrosine-kinase-dependent tumors 1149:1189 receptor-tyrosine-kinase-dependent tumors 1149:1189 These results identify OST inhibition as a potential therapeutic approach for treating receptor-tyrosine-kinase-dependent tumors and provides a chemical probe for reversibly regulating N-linked glycosylation in mammalian cells. 27694802 2 50 theme cell-permeable 407:420 arg1 NGI-1 433:437 NGI-1 433:437 NGI-1 433:437 To identify small molecules that inhibit new targets in this biosynthetic pathway, we initiated a cell-based high-throughput screen and lead-compound-optimization campaign that delivered a cell-permeable inhibitor, NGI-1. 27694802 2 50 theme cell-permeable 407:420 arg1 inhibitor 422:430 a cell-permeable inhibitor 405:430 a cell-permeable inhibitor 405:430 To identify small molecules that inhibit new targets in this biosynthetic pathway, we initiated a cell-based high-throughput screen and lead-compound-optimization campaign that delivered a cell-permeable inhibitor, NGI-1. 27694802 2 51 theme new 259:261 arg1 targets 263:269 new targets 259:269 new targets 259:269 To identify small molecules that inhibit new targets in this biosynthetic pathway, we initiated a cell-based high-throughput screen and lead-compound-optimization campaign that delivered a cell-permeable inhibitor, NGI-1. 27694802 3 52 theme recipient 581:589 arg1 proteins 591:598 recipient proteins 581:598 recipient proteins 581:598 NGI-1 targets oligosaccharyltransferase (OST), a hetero-oligomeric enzyme that exists in multiple isoforms and transfers oligosaccharides to recipient proteins. 27486435 10 0 theme protein 1414:1420 arg1 synthesis 1422:1430 protein synthesis 1414:1430 protein synthesis 1414:1430 Nonetheless, when protein synthesis was blocked with cycloheximide, MRAP was rapidly degraded even when MG132 was included and all lysines were replaced by arginines, implicating non-proteasomal degradation pathways. 27486435 1 1 theme melanocortin 150:161 arg1 receptors 171:179 melanocortin 2 (MC2) receptors 150:179 melanocortin 2 (MC2) receptors 150:179 Melanocortin 2 receptor accessory protein (MRAP) facilitates trafficking of melanocortin 2 (MC2) receptors and is essential for ACTH binding and signaling. 27486435 9 2 theme other 1377:1381 arg1 acids 1389:1393 other amino acids 1377:1393 other amino acids 1377:1393 The amount of MRAP was increased by the proteasome inhibitor MG132 and MRAP underwent ubiquitylation on lysine and other amino acids. 27486435 5 3 theme mammalian 941:949 arg1 cells 951:955 mammalian cells 941:955 mammalian cells together with either cytoplasmic or endoplasmic reticulum-targeted biotin ligase 941:1036 We inserted biotin ligase acceptor peptides at the N- or C-terminal ends of MRAP and expressed the modified proteins in mammalian cells together with either cytoplasmic or endoplasmic reticulum-targeted biotin ligase. 27486435 5 4 theme modified 920:927 arg1 proteins 929:936 the modified proteins 916:936 the modified proteins 916:936 We inserted biotin ligase acceptor peptides at the N- or C-terminal ends of MRAP and expressed the modified proteins in mammalian cells together with either cytoplasmic or endoplasmic reticulum-targeted biotin ligase. 27486435 5 5 theme MRAP 897:900 arg1 N- 872:873 N- 872:873 N- 872:873 We inserted biotin ligase acceptor peptides at the N- or C-terminal ends of MRAP and expressed the modified proteins in mammalian cells together with either cytoplasmic or endoplasmic reticulum-targeted biotin ligase. 27486435 5 5 theme MRAP 897:900 arg1 ends 889:892 C-terminal ends 878:892 C-terminal ends 878:892 We inserted biotin ligase acceptor peptides at the N- or C-terminal ends of MRAP and expressed the modified proteins in mammalian cells together with either cytoplasmic or endoplasmic reticulum-targeted biotin ligase. 27486435 4 6 theme orientations 716:727 arg1 protomers 694:702 MRAP protomers 689:702 MRAP protomers of opposite orientations based on their N-linked glycosylation 689:765 To answer these questions, we developed an approach that capitalizes on the specificity of bacterial biotin ligase, which adds biotin to lysine in a short acceptor peptide sequence; the distinct mobility of MRAP protomers of opposite orientations based on their N-linked glycosylation; and the ease of identifying biotin-labeled proteins. 27486435 2 7 theme domain 261:266 arg1 MRAP 230:233 MRAP 230:233 MRAP 230:233 MRAP is a single transmembrane domain protein that forms antiparallel homodimers. 27486435 2 7 theme domain 261:266 arg1 protein 268:274 a single transmembrane domain protein 238:274 a single transmembrane domain protein that forms antiparallel homodimers 238:309 MRAP is a single transmembrane domain protein that forms antiparallel homodimers. 27486435 4 8 theme distinct 668:675 arg1 mobility 677:684 the distinct mobility 664:684 the distinct mobility of MRAP protomers of opposite orientations based on their N-linked glycosylation 664:765 To answer these questions, we developed an approach that capitalizes on the specificity of bacterial biotin ligase, which adds biotin to lysine in a short acceptor peptide sequence; the distinct mobility of MRAP protomers of opposite orientations based on their N-linked glycosylation; and the ease of identifying biotin-labeled proteins. 27486435 2 9 theme transmembrane 247:259 arg1 MRAP 230:233 MRAP 230:233 MRAP 230:233 MRAP is a single transmembrane domain protein that forms antiparallel homodimers. 27486435 2 9 theme transmembrane 247:259 arg1 protein 268:274 a single transmembrane domain protein 238:274 a single transmembrane domain protein that forms antiparallel homodimers 238:309 MRAP is a single transmembrane domain protein that forms antiparallel homodimers. 27486435 5 10 theme ligase 840:845 arg1 peptides 856:863 biotin ligase acceptor peptides 833:863 biotin ligase acceptor peptides 833:863 We inserted biotin ligase acceptor peptides at the N- or C-terminal ends of MRAP and expressed the modified proteins in mammalian cells together with either cytoplasmic or endoplasmic reticulum-targeted biotin ligase. 27486435 0 11 theme Accessory 45:53 arg1 Protein 55:61 the Melanocortin-2 Receptor Accessory Protein 17:61 the Melanocortin-2 Receptor Accessory Protein 17:61 Dual Topology of the Melanocortin-2 Receptor Accessory Protein Is Stable. 27486435 9 12 theme amino 1383:1387 arg1 acids 1389:1393 other amino acids 1377:1393 other amino acids 1377:1393 The amount of MRAP was increased by the proteasome inhibitor MG132 and MRAP underwent ubiquitylation on lysine and other amino acids. 27486435 4 13 theme biotin-labeled 796:809 arg1 proteins 811:818 biotin-labeled proteins 796:818 biotin-labeled proteins 796:818 To answer these questions, we developed an approach that capitalizes on the specificity of bacterial biotin ligase, which adds biotin to lysine in a short acceptor peptide sequence; the distinct mobility of MRAP protomers of opposite orientations based on their N-linked glycosylation; and the ease of identifying biotin-labeled proteins. 27486435 1 14 theme Melanocortin 74:85 arg1 MRAP 117:120 MRAP 117:120 MRAP 117:120 Melanocortin 2 receptor accessory protein (MRAP) facilitates trafficking of melanocortin 2 (MC2) receptors and is essential for ACTH binding and signaling. 27486435 1 14 theme Melanocortin 74:85 arg1 protein 108:114 Melanocortin 2 receptor accessory protein 74:114 Melanocortin 2 receptor accessory protein (MRAP) 74:121 Melanocortin 2 receptor accessory protein (MRAP) facilitates trafficking of melanocortin 2 (MC2) receptors and is essential for ACTH binding and signaling. 27486435 1 15 theme MC2 166:168 arg1 receptors 171:179 melanocortin 2 (MC2) receptors 150:179 melanocortin 2 (MC2) receptors 150:179 Melanocortin 2 receptor accessory protein (MRAP) facilitates trafficking of melanocortin 2 (MC2) receptors and is essential for ACTH binding and signaling. 27486435 2 16 theme antiparallel 287:298 arg1 homodimers 300:309 antiparallel homodimers 287:309 antiparallel homodimers 287:309 MRAP is a single transmembrane domain protein that forms antiparallel homodimers. 27486435 4 17 theme protomers 694:702 arg1 sequence 654:661 a short acceptor peptide sequence 629:661 a short acceptor peptide sequence 629:661 To answer these questions, we developed an approach that capitalizes on the specificity of bacterial biotin ligase, which adds biotin to lysine in a short acceptor peptide sequence; the distinct mobility of MRAP protomers of opposite orientations based on their N-linked glycosylation; and the ease of identifying biotin-labeled proteins. 27486435 4 17 theme protomers 694:702 arg1 ease 776:779 the ease 772:779 the ease of identifying biotin-labeled proteins 772:818 To answer these questions, we developed an approach that capitalizes on the specificity of bacterial biotin ligase, which adds biotin to lysine in a short acceptor peptide sequence; the distinct mobility of MRAP protomers of opposite orientations based on their N-linked glycosylation; and the ease of identifying biotin-labeled proteins. 27486435 4 17 theme protomers 694:702 arg1 mobility 677:684 the distinct mobility 664:684 the distinct mobility of MRAP protomers of opposite orientations based on their N-linked glycosylation 664:765 To answer these questions, we developed an approach that capitalizes on the specificity of bacterial biotin ligase, which adds biotin to lysine in a short acceptor peptide sequence; the distinct mobility of MRAP protomers of opposite orientations based on their N-linked glycosylation; and the ease of identifying biotin-labeled proteins. 27486435 6 18 theme dual 1052:1055 arg1 topology 1057:1064 dual topology 1052:1064 dual topology 1052:1064 MRAP assumed dual topology early in biosynthesis in both CHO and OS3 adrenal cells. 27486435 4 19 theme short 631:635 arg1 sequence 654:661 a short acceptor peptide sequence 629:661 a short acceptor peptide sequence 629:661 To answer these questions, we developed an approach that capitalizes on the specificity of bacterial biotin ligase, which adds biotin to lysine in a short acceptor peptide sequence; the distinct mobility of MRAP protomers of opposite orientations based on their N-linked glycosylation; and the ease of identifying biotin-labeled proteins. 27486435 0 20 theme Dual 0:3 arg1 Topology 5:12 Dual Topology 0:12 Dual Topology of the Melanocortin-2 Receptor Accessory Protein 0:61 Dual Topology of the Melanocortin-2 Receptor Accessory Protein Is Stable. 27486435 10 21 theme non-proteasomal 1575:1589 arg1 pathways 1603:1610 non-proteasomal degradation pathways 1575:1610 non-proteasomal degradation pathways 1575:1610 Nonetheless, when protein synthesis was blocked with cycloheximide, MRAP was rapidly degraded even when MG132 was included and all lysines were replaced by arginines, implicating non-proteasomal degradation pathways. 27486435 1 22 theme receptor 89:96 arg1 MRAP 117:120 MRAP 117:120 MRAP 117:120 Melanocortin 2 receptor accessory protein (MRAP) facilitates trafficking of melanocortin 2 (MC2) receptors and is essential for ACTH binding and signaling. 27486435 1 22 theme receptor 89:96 arg1 protein 108:114 Melanocortin 2 receptor accessory protein 74:114 Melanocortin 2 receptor accessory protein (MRAP) 74:121 Melanocortin 2 receptor accessory protein (MRAP) facilitates trafficking of melanocortin 2 (MC2) receptors and is essential for ACTH binding and signaling. 27486435 1 23 theme receptors 171:179 arg1 trafficking 135:145 trafficking 135:145 trafficking of melanocortin 2 (MC2) receptors 135:179 Melanocortin 2 receptor accessory protein (MRAP) facilitates trafficking of melanocortin 2 (MC2) receptors and is essential for ACTH binding and signaling. 27486435 4 24 theme MRAP 689:692 arg1 protomers 694:702 MRAP protomers 689:702 MRAP protomers of opposite orientations based on their N-linked glycosylation 689:765 To answer these questions, we developed an approach that capitalizes on the specificity of bacterial biotin ligase, which adds biotin to lysine in a short acceptor peptide sequence; the distinct mobility of MRAP protomers of opposite orientations based on their N-linked glycosylation; and the ease of identifying biotin-labeled proteins. 27486435 1 25 theme accessory 98:106 arg1 MRAP 117:120 MRAP 117:120 MRAP 117:120 Melanocortin 2 receptor accessory protein (MRAP) facilitates trafficking of melanocortin 2 (MC2) receptors and is essential for ACTH binding and signaling. 27486435 1 25 theme accessory 98:106 arg1 protein 108:114 Melanocortin 2 receptor accessory protein 74:114 Melanocortin 2 receptor accessory protein (MRAP) 74:121 Melanocortin 2 receptor accessory protein (MRAP) facilitates trafficking of melanocortin 2 (MC2) receptors and is essential for ACTH binding and signaling. 27486435 3 26 theme dual 360:363 arg1 topology 365:372 this dual topology 355:372 this dual topology 355:372 These studies ask when MRAP first acquires this dual topology, whether MRAP architecture is static or stable, and whether the accessory protein undergoes rapid turnover. 27486435 9 27 theme proteasome 1302:1311 arg1 MG132 1323:1327 the proteasome inhibitor MG132 1298:1327 the proteasome inhibitor MG132 1298:1327 The amount of MRAP was increased by the proteasome inhibitor MG132 and MRAP underwent ubiquitylation on lysine and other amino acids. 27486435 3 28 theme accessory 438:446 arg1 protein 448:454 the accessory protein 434:454 the accessory protein 434:454 These studies ask when MRAP first acquires this dual topology, whether MRAP architecture is static or stable, and whether the accessory protein undergoes rapid turnover. 27486435 0 29 theme Receptor 36:43 arg1 Protein 55:61 the Melanocortin-2 Receptor Accessory Protein 17:61 the Melanocortin-2 Receptor Accessory Protein 17:61 Dual Topology of the Melanocortin-2 Receptor Accessory Protein Is Stable. 27486435 9 30 theme inhibitor 1313:1321 arg1 MG132 1323:1327 the proteasome inhibitor MG132 1298:1327 the proteasome inhibitor MG132 1298:1327 The amount of MRAP was increased by the proteasome inhibitor MG132 and MRAP underwent ubiquitylation on lysine and other amino acids. 27486435 9 31 theme MRAP 1276:1279 arg1 MRAP 1276:1279 MRAP 1276:1279 MRAP 1276:1279 The amount of MRAP was increased by the proteasome inhibitor MG132 and MRAP underwent ubiquitylation on lysine and other amino acids. 27486435 9 31 theme MRAP 1276:1279 arg1 amount 1266:1271 The amount 1262:1271 The amount of MRAP 1262:1279 The amount of MRAP was increased by the proteasome inhibitor MG132 and MRAP underwent ubiquitylation on lysine and other amino acids. 27486435 5 32 theme cytoplasmic 978:988 arg1 ligase 1031:1036 either cytoplasmic or endoplasmic reticulum-targeted biotin ligase 971:1036 either cytoplasmic or endoplasmic reticulum-targeted biotin ligase 971:1036 We inserted biotin ligase acceptor peptides at the N- or C-terminal ends of MRAP and expressed the modified proteins in mammalian cells together with either cytoplasmic or endoplasmic reticulum-targeted biotin ligase. 27486435 5 33 theme acceptor 847:854 arg1 peptides 856:863 biotin ligase acceptor peptides 833:863 biotin ligase acceptor peptides 833:863 We inserted biotin ligase acceptor peptides at the N- or C-terminal ends of MRAP and expressed the modified proteins in mammalian cells together with either cytoplasmic or endoplasmic reticulum-targeted biotin ligase. 27486435 8 34 theme CHO 1251:1253 arg1 cells 1255:1259 CHO cells 1251:1259 CHO cells 1251:1259 Despite its conformational stability, MRAP displayed a half-life of under 2 h in CHO cells. 27486435 0 35 theme Melanocortin-2 21:34 arg1 Protein 55:61 the Melanocortin-2 Receptor Accessory Protein 17:61 the Melanocortin-2 Receptor Accessory Protein 17:61 Dual Topology of the Melanocortin-2 Receptor Accessory Protein Is Stable. 27486435 8 36 theme conformational 1182:1195 arg1 stability 1197:1205 its conformational stability 1178:1205 its conformational stability 1178:1205 Despite its conformational stability, MRAP displayed a half-life of under 2 h in CHO cells. 27486435 4 37 link N-linked 744:751 arg1 glycosylation 753:765 their N-linked glycosylation 738:765 their N-linked glycosylation 738:765 To answer these questions, we developed an approach that capitalizes on the specificity of bacterial biotin ligase, which adds biotin to lysine in a short acceptor peptide sequence; the distinct mobility of MRAP protomers of opposite orientations based on their N-linked glycosylation; and the ease of identifying biotin-labeled proteins. 27486435 0 38 theme Protein 55:61 arg1 Topology 5:12 Dual Topology 0:12 Dual Topology of the Melanocortin-2 Receptor Accessory Protein 0:61 Dual Topology of the Melanocortin-2 Receptor Accessory Protein Is Stable. 27486435 6 39 dep both 1091:1094 arg1 CHO 1096:1098 CHO 1096:1098 CHO 1096:1098 MRAP assumed dual topology early in biosynthesis in both CHO and OS3 adrenal cells. 27486435 5 40 dep N- 872:873 arg1 the 868:870 the 868:870 the 868:870 We inserted biotin ligase acceptor peptides at the N- or C-terminal ends of MRAP and expressed the modified proteins in mammalian cells together with either cytoplasmic or endoplasmic reticulum-targeted biotin ligase. 27486435 3 41 theme rapid 466:470 arg1 turnover 472:479 rapid turnover 466:479 rapid turnover 466:479 These studies ask when MRAP first acquires this dual topology, whether MRAP architecture is static or stable, and whether the accessory protein undergoes rapid turnover. 27486435 3 42 theme MRAP 383:386 arg1 architecture 388:399 MRAP architecture 383:399 MRAP architecture 383:399 These studies ask when MRAP first acquires this dual topology, whether MRAP architecture is static or stable, and whether the accessory protein undergoes rapid turnover. 27486435 5 43 theme biotin 1024:1029 arg1 ligase 1031:1036 either cytoplasmic or endoplasmic reticulum-targeted biotin ligase 971:1036 either cytoplasmic or endoplasmic reticulum-targeted biotin ligase 971:1036 We inserted biotin ligase acceptor peptides at the N- or C-terminal ends of MRAP and expressed the modified proteins in mammalian cells together with either cytoplasmic or endoplasmic reticulum-targeted biotin ligase. 27486435 5 44 theme reticulum-targeted 1005:1022 arg1 ligase 1031:1036 either cytoplasmic or endoplasmic reticulum-targeted biotin ligase 971:1036 either cytoplasmic or endoplasmic reticulum-targeted biotin ligase 971:1036 We inserted biotin ligase acceptor peptides at the N- or C-terminal ends of MRAP and expressed the modified proteins in mammalian cells together with either cytoplasmic or endoplasmic reticulum-targeted biotin ligase. 27486435 5 45 theme C-terminal 878:887 arg1 ends 889:892 C-terminal ends 878:892 C-terminal ends 878:892 We inserted biotin ligase acceptor peptides at the N- or C-terminal ends of MRAP and expressed the modified proteins in mammalian cells together with either cytoplasmic or endoplasmic reticulum-targeted biotin ligase. 27486435 4 46 theme opposite 707:714 arg1 orientations 716:727 opposite orientations 707:727 opposite orientations based on their N-linked glycosylation 707:765 To answer these questions, we developed an approach that capitalizes on the specificity of bacterial biotin ligase, which adds biotin to lysine in a short acceptor peptide sequence; the distinct mobility of MRAP protomers of opposite orientations based on their N-linked glycosylation; and the ease of identifying biotin-labeled proteins. 27486435 1 47 theme ACTH 202:205 arg1 binding 207:213 ACTH binding 202:213 ACTH binding 202:213 Melanocortin 2 receptor accessory protein (MRAP) facilitates trafficking of melanocortin 2 (MC2) receptors and is essential for ACTH binding and signaling. 27486435 2 48 theme single 240:245 arg1 MRAP 230:233 MRAP 230:233 MRAP 230:233 MRAP is a single transmembrane domain protein that forms antiparallel homodimers. 27486435 2 48 theme single 240:245 arg1 protein 268:274 a single transmembrane domain protein 238:274 a single transmembrane domain protein that forms antiparallel homodimers 238:309 MRAP is a single transmembrane domain protein that forms antiparallel homodimers. 27486435 6 49 dep cells 1116:1120 arg1 both 1091:1094 both 1091:1094 both 1091:1094 MRAP assumed dual topology early in biosynthesis in both CHO and OS3 adrenal cells. 27486435 6 49 dep cells 1116:1120 arg1 adrenal 1108:1114 adrenal 1108:1114 adrenal 1108:1114 MRAP assumed dual topology early in biosynthesis in both CHO and OS3 adrenal cells. 27486435 4 50 theme N-linked 744:751 arg1 glycosylation 753:765 their N-linked glycosylation 738:765 their N-linked glycosylation 738:765 To answer these questions, we developed an approach that capitalizes on the specificity of bacterial biotin ligase, which adds biotin to lysine in a short acceptor peptide sequence; the distinct mobility of MRAP protomers of opposite orientations based on their N-linked glycosylation; and the ease of identifying biotin-labeled proteins. 27486435 6 51 from biosynthesis 1075:1086 arg1 cells 1116:1120 both CHO and OS3 adrenal cells 1091:1120 both CHO and OS3 adrenal cells 1091:1120 MRAP assumed dual topology early in biosynthesis in both CHO and OS3 adrenal cells. 27486435 4 52 theme acceptor 637:644 arg1 sequence 654:661 a short acceptor peptide sequence 629:661 a short acceptor peptide sequence 629:661 To answer these questions, we developed an approach that capitalizes on the specificity of bacterial biotin ligase, which adds biotin to lysine in a short acceptor peptide sequence; the distinct mobility of MRAP protomers of opposite orientations based on their N-linked glycosylation; and the ease of identifying biotin-labeled proteins. 27486435 4 53 theme bacterial 573:581 arg1 ligase 590:595 bacterial biotin ligase 573:595 bacterial biotin ligase 573:595 To answer these questions, we developed an approach that capitalizes on the specificity of bacterial biotin ligase, which adds biotin to lysine in a short acceptor peptide sequence; the distinct mobility of MRAP protomers of opposite orientations based on their N-linked glycosylation; and the ease of identifying biotin-labeled proteins. 27486435 4 54 theme peptide 646:652 arg1 sequence 654:661 a short acceptor peptide sequence 629:661 a short acceptor peptide sequence 629:661 To answer these questions, we developed an approach that capitalizes on the specificity of bacterial biotin ligase, which adds biotin to lysine in a short acceptor peptide sequence; the distinct mobility of MRAP protomers of opposite orientations based on their N-linked glycosylation; and the ease of identifying biotin-labeled proteins. 27486435 5 55 theme biotin 833:838 arg1 ligase 840:845 biotin ligase 833:845 biotin ligase acceptor peptides 833:863 We inserted biotin ligase acceptor peptides at the N- or C-terminal ends of MRAP and expressed the modified proteins in mammalian cells together with either cytoplasmic or endoplasmic reticulum-targeted biotin ligase. 27486435 10 56 theme degradation 1591:1601 arg1 pathways 1603:1610 non-proteasomal degradation pathways 1575:1610 non-proteasomal degradation pathways 1575:1610 Nonetheless, when protein synthesis was blocked with cycloheximide, MRAP was rapidly degraded even when MG132 was included and all lysines were replaced by arginines, implicating non-proteasomal degradation pathways. 27486435 7 57 theme MRAP 1141:1144 arg1 orientation 1146:1156 MRAP orientation 1141:1156 MRAP orientation 1141:1156 Once established, MRAP orientation was stable. 27486435 8 58 from 2 h 1244:1246 arg1 cells 1255:1259 CHO cells 1251:1259 CHO cells 1251:1259 Despite its conformational stability, MRAP displayed a half-life of under 2 h in CHO cells. 27486435 4 59 theme biotin 583:588 arg1 ligase 590:595 bacterial biotin ligase 573:595 bacterial biotin ligase 573:595 To answer these questions, we developed an approach that capitalizes on the specificity of bacterial biotin ligase, which adds biotin to lysine in a short acceptor peptide sequence; the distinct mobility of MRAP protomers of opposite orientations based on their N-linked glycosylation; and the ease of identifying biotin-labeled proteins. 27486435 4 60 theme ligase 590:595 arg1 specificity 558:568 the specificity 554:568 the specificity of bacterial biotin ligase, which adds biotin to lysine in a short acceptor peptide sequence; the distinct mobility of MRAP protomers of opposite orientations based on their N-linked glycosylation; and the ease of identifying biotin-labeled proteins 554:818 To answer these questions, we developed an approach that capitalizes on the specificity of bacterial biotin ligase, which adds biotin to lysine in a short acceptor peptide sequence; the distinct mobility of MRAP protomers of opposite orientations based on their N-linked glycosylation; and the ease of identifying biotin-labeled proteins. 26992607 5 0 theme such 689:692 arg1 studies 694:700 such studies 689:700 such studies 689:700 Traditional analytical methods, which are used to measure glycans in such studies, do not determine the number of HM glycans per antibody. 26992607 1 1 theme heavy 131:135 arg1 chain 137:141 each heavy chain 126:141 each heavy chain 126:141 IgG antibodies contain N-linked glycans on the Fc portion of each heavy chain. 26992607 6 2 from levels 831:836 arg1 antibodies 887:896 antibodies 887:896 antibodies in human pharmacokinetic serum samples 887:935 With a sensitive method designed to measure HM pairing, we followed the levels of symmetrically and asymmetrically paired HM on antibodies in human pharmacokinetic serum samples to determine the impact of Fc HM glycan pairing on therapeutic human IgG clearance in humans. 26992607 4 3 theme paired 537:542 arg1 forms 547:551 symmetrically vs. asymmetrically paired HM forms 504:551 symmetrically vs. asymmetrically paired HM forms 504:551 Previous studies showing that high mannose forms result in faster mAb clearance in humans were incapable of differentiating the impact of symmetrically vs. asymmetrically paired HM forms, and, therefore, the effect of pairing on clearance was not clear. 26992607 2 4 from glycan 148:153 arg1 chain 168:172 one heavy chain 158:172 one heavy chain 158:172 The glycan on one heavy chain can either match the glycan on the other heavy chain (symmetrical pairing) or be different (asymmetrical pairing). 26992607 7 5 from effect 1101:1106 arg1 clearance 1111:1119 clearance 1111:1119 clearance 1111:1119 The two HM paired forms cleared at the same rate, indicating that the effect on clearance was not proportional to the degree of modification. 26992607 8 6 theme relative 1285:1292 arg1 levels 1294:1299 their relative levels 1279:1299 their relative levels 1279:1299 Since both forms can exist on therapeutic antibodies and the ratio can differ between products, measuring their relative levels is necessary to properly estimate effects on clearance. 26992607 1 7 theme chain 137:141 arg1 portion 115:121 the Fc portion 108:121 the Fc portion of each heavy chain 108:141 IgG antibodies contain N-linked glycans on the Fc portion of each heavy chain. 26992607 3 8 theme Fc 295:296 arg1 glycans 298:304 These Fc glycans 289:304 These Fc glycans 289:304 These Fc glycans influence effector functions and can alter clearance rates. 26992607 0 9 from Effect 0:5 arg1 clearance 54:62 IgG antibody clearance 41:62 IgG antibody clearance 41:62 Effect of high mannose glycan pairing on IgG antibody clearance. 26992607 5 10 used used 662:665 arg2 methods 643:649 Traditional analytical methods 620:649 Traditional analytical methods 620:649 Traditional analytical methods, which are used to measure glycans in such studies, do not determine the number of HM glycans per antibody. 26992607 4 11 theme forms 547:551 arg1 impact 494:499 the impact 490:499 the impact of symmetrically vs. asymmetrically paired HM forms 490:551 Previous studies showing that high mannose forms result in faster mAb clearance in humans were incapable of differentiating the impact of symmetrically vs. asymmetrically paired HM forms, and, therefore, the effect of pairing on clearance was not clear. 26992607 6 12 theme HM 803:804 arg1 pairing 806:812 HM pairing 803:812 HM pairing 803:812 With a sensitive method designed to measure HM pairing, we followed the levels of symmetrically and asymmetrically paired HM on antibodies in human pharmacokinetic serum samples to determine the impact of Fc HM glycan pairing on therapeutic human IgG clearance in humans. 26992607 4 13 from clearance 436:444 arg1 humans 449:454 humans 449:454 humans were incapable of differentiating the impact of symmetrically vs. asymmetrically paired HM forms 449:551 Previous studies showing that high mannose forms result in faster mAb clearance in humans were incapable of differentiating the impact of symmetrically vs. asymmetrically paired HM forms, and, therefore, the effect of pairing on clearance was not clear. 26992607 7 14 theme HM 1039:1040 arg1 forms 1049:1053 The two HM paired forms 1031:1053 The two HM paired forms 1031:1053 The two HM paired forms cleared at the same rate, indicating that the effect on clearance was not proportional to the degree of modification. 26992607 2 15 theme symmetrical 228:238 arg1 chain 221:225 the other heavy chain 205:225 the other heavy chain (symmetrical pairing) 205:247 The glycan on one heavy chain can either match the glycan on the other heavy chain (symmetrical pairing) or be different (asymmetrical pairing). 26992607 2 15 theme symmetrical 228:238 arg1 pairing 240:246 symmetrical pairing 228:246 symmetrical pairing 228:246 The glycan on one heavy chain can either match the glycan on the other heavy chain (symmetrical pairing) or be different (asymmetrical pairing). 26992607 4 16 theme HM 544:545 arg1 forms 547:551 symmetrically vs. asymmetrically paired HM forms 504:551 symmetrically vs. asymmetrically paired HM forms 504:551 Previous studies showing that high mannose forms result in faster mAb clearance in humans were incapable of differentiating the impact of symmetrically vs. asymmetrically paired HM forms, and, therefore, the effect of pairing on clearance was not clear. 26992607 7 17 theme same 1070:1073 arg1 rate 1075:1078 the same rate 1066:1078 the same rate 1066:1078 The two HM paired forms cleared at the same rate, indicating that the effect on clearance was not proportional to the degree of modification. 26992607 6 18 from antibodies 887:896 arg1 samples 929:935 human pharmacokinetic serum samples 901:935 human pharmacokinetic serum samples 901:935 With a sensitive method designed to measure HM pairing, we followed the levels of symmetrically and asymmetrically paired HM on antibodies in human pharmacokinetic serum samples to determine the impact of Fc HM glycan pairing on therapeutic human IgG clearance in humans. 26992607 6 19 theme therapeutic 988:998 arg1 clearance 1010:1018 therapeutic human IgG clearance 988:1018 therapeutic human IgG clearance in humans 988:1028 With a sensitive method designed to measure HM pairing, we followed the levels of symmetrically and asymmetrically paired HM on antibodies in human pharmacokinetic serum samples to determine the impact of Fc HM glycan pairing on therapeutic human IgG clearance in humans. 26992607 6 20 theme pairing 977:983 arg1 impact 954:959 the impact 950:959 the impact of Fc HM glycan pairing on therapeutic human IgG clearance in humans 950:1028 With a sensitive method designed to measure HM pairing, we followed the levels of symmetrically and asymmetrically paired HM on antibodies in human pharmacokinetic serum samples to determine the impact of Fc HM glycan pairing on therapeutic human IgG clearance in humans. 26992607 4 21 theme mAb 432:434 arg1 clearance 436:444 faster mAb clearance 425:444 faster mAb clearance in humans were incapable of differentiating the impact of symmetrically vs. asymmetrically paired HM forms 425:551 Previous studies showing that high mannose forms result in faster mAb clearance in humans were incapable of differentiating the impact of symmetrically vs. asymmetrically paired HM forms, and, therefore, the effect of pairing on clearance was not clear. 26992607 0 22 theme pairing 30:36 arg1 Effect 0:5 Effect 0:5 Effect of high mannose glycan pairing on IgG antibody clearance. 0:63 Effect of high mannose glycan pairing on IgG antibody clearance. 26992607 1 23 theme IgG 65:67 arg1 antibodies 69:78 IgG antibodies 65:78 IgG antibodies 65:78 IgG antibodies contain N-linked glycans on the Fc portion of each heavy chain. 26992607 2 24 from glycan 195:200 arg1 chain 221:225 the other heavy chain 205:225 the other heavy chain (symmetrical pairing) 205:247 The glycan on one heavy chain can either match the glycan on the other heavy chain (symmetrical pairing) or be different (asymmetrical pairing). 26992607 2 24 from glycan 195:200 arg1 pairing 240:246 symmetrical pairing 228:246 symmetrical pairing 228:246 The glycan on one heavy chain can either match the glycan on the other heavy chain (symmetrical pairing) or be different (asymmetrical pairing). 26992607 4 25 theme pairing 584:590 arg1 effect 574:579 the effect 570:579 the effect of pairing on clearance 570:603 Previous studies showing that high mannose forms result in faster mAb clearance in humans were incapable of differentiating the impact of symmetrically vs. asymmetrically paired HM forms, and, therefore, the effect of pairing on clearance was not clear. 26992607 4 25 theme pairing 584:590 arg1 clear 613:617 clear 613:617 clear 613:617 Previous studies showing that high mannose forms result in faster mAb clearance in humans were incapable of differentiating the impact of symmetrically vs. asymmetrically paired HM forms, and, therefore, the effect of pairing on clearance was not clear. 26992607 4 26 theme faster 425:430 arg1 clearance 436:444 faster mAb clearance 425:444 faster mAb clearance in humans were incapable of differentiating the impact of symmetrically vs. asymmetrically paired HM forms 425:551 Previous studies showing that high mannose forms result in faster mAb clearance in humans were incapable of differentiating the impact of symmetrically vs. asymmetrically paired HM forms, and, therefore, the effect of pairing on clearance was not clear. 26992607 8 27 from effects 1335:1341 arg1 clearance 1346:1354 clearance 1346:1354 clearance 1346:1354 Since both forms can exist on therapeutic antibodies and the ratio can differ between products, measuring their relative levels is necessary to properly estimate effects on clearance. 26992607 6 28 theme HM 967:968 arg1 pairing 977:983 Fc HM glycan pairing 964:983 Fc HM glycan pairing 964:983 With a sensitive method designed to measure HM pairing, we followed the levels of symmetrically and asymmetrically paired HM on antibodies in human pharmacokinetic serum samples to determine the impact of Fc HM glycan pairing on therapeutic human IgG clearance in humans. 26992607 6 29 theme HM 881:882 arg1 levels 831:836 the levels 827:836 the levels of symmetrically and asymmetrically paired HM on antibodies in human pharmacokinetic serum samples 827:935 With a sensitive method designed to measure HM pairing, we followed the levels of symmetrically and asymmetrically paired HM on antibodies in human pharmacokinetic serum samples to determine the impact of Fc HM glycan pairing on therapeutic human IgG clearance in humans. 26992607 6 30 theme human 901:905 arg1 samples 929:935 human pharmacokinetic serum samples 901:935 human pharmacokinetic serum samples 901:935 With a sensitive method designed to measure HM pairing, we followed the levels of symmetrically and asymmetrically paired HM on antibodies in human pharmacokinetic serum samples to determine the impact of Fc HM glycan pairing on therapeutic human IgG clearance in humans. 26992607 6 31 theme Fc 964:965 arg1 pairing 977:983 Fc HM glycan pairing 964:983 Fc HM glycan pairing 964:983 With a sensitive method designed to measure HM pairing, we followed the levels of symmetrically and asymmetrically paired HM on antibodies in human pharmacokinetic serum samples to determine the impact of Fc HM glycan pairing on therapeutic human IgG clearance in humans. 26992607 0 32 theme mannose 15:21 arg1 pairing 30:36 high mannose glycan pairing 10:36 high mannose glycan pairing 10:36 Effect of high mannose glycan pairing on IgG antibody clearance. 26992607 6 33 theme paired 874:879 arg1 HM 881:882 symmetrically and asymmetrically paired HM 841:882 symmetrically and asymmetrically paired HM 841:882 With a sensitive method designed to measure HM pairing, we followed the levels of symmetrically and asymmetrically paired HM on antibodies in human pharmacokinetic serum samples to determine the impact of Fc HM glycan pairing on therapeutic human IgG clearance in humans. 26992607 5 34 theme analytical 632:641 arg1 methods 643:649 Traditional analytical methods 620:649 Traditional analytical methods 620:649 Traditional analytical methods, which are used to measure glycans in such studies, do not determine the number of HM glycans per antibody. 26992607 6 35 from impact 954:959 arg1 clearance 1010:1018 therapeutic human IgG clearance 988:1018 therapeutic human IgG clearance in humans 988:1028 With a sensitive method designed to measure HM pairing, we followed the levels of symmetrically and asymmetrically paired HM on antibodies in human pharmacokinetic serum samples to determine the impact of Fc HM glycan pairing on therapeutic human IgG clearance in humans. 26992607 1 36 theme N-linked 88:95 arg1 glycans 97:103 N-linked glycans 88:103 N-linked glycans 88:103 IgG antibodies contain N-linked glycans on the Fc portion of each heavy chain. 26992607 4 37 from effect 574:579 arg1 clearance 595:603 clearance 595:603 clearance 595:603 Previous studies showing that high mannose forms result in faster mAb clearance in humans were incapable of differentiating the impact of symmetrically vs. asymmetrically paired HM forms, and, therefore, the effect of pairing on clearance was not clear. 26992607 5 38 theme glycans 737:743 arg1 number 724:729 the number 720:729 the number of HM glycans per antibody 720:756 Traditional analytical methods, which are used to measure glycans in such studies, do not determine the number of HM glycans per antibody. 26992607 0 39 theme high 10:13 arg1 pairing 30:36 high mannose glycan pairing 10:36 high mannose glycan pairing 10:36 Effect of high mannose glycan pairing on IgG antibody clearance. 26992607 4 40 theme high 396:399 arg1 forms 409:413 high mannose forms 396:413 high mannose forms 396:413 Previous studies showing that high mannose forms result in faster mAb clearance in humans were incapable of differentiating the impact of symmetrically vs. asymmetrically paired HM forms, and, therefore, the effect of pairing on clearance was not clear. 26992607 3 41 theme clearance 349:357 arg1 rates 359:363 clearance rates 349:363 clearance rates 349:363 These Fc glycans influence effector functions and can alter clearance rates. 26992607 6 42 theme sensitive 766:774 arg1 method 776:781 a sensitive method 764:781 a sensitive method designed to measure HM pairing 764:812 With a sensitive method designed to measure HM pairing, we followed the levels of symmetrically and asymmetrically paired HM on antibodies in human pharmacokinetic serum samples to determine the impact of Fc HM glycan pairing on therapeutic human IgG clearance in humans. 26992607 7 43 theme modification 1159:1170 arg1 degree 1149:1154 the degree 1145:1154 the degree of modification 1145:1170 The two HM paired forms cleared at the same rate, indicating that the effect on clearance was not proportional to the degree of modification. 26992607 0 44 theme glycan 23:28 arg1 pairing 30:36 high mannose glycan pairing 10:36 high mannose glycan pairing 10:36 Effect of high mannose glycan pairing on IgG antibody clearance. 26992607 7 45 theme paired 1042:1047 arg1 forms 1049:1053 The two HM paired forms 1031:1053 The two HM paired forms 1031:1053 The two HM paired forms cleared at the same rate, indicating that the effect on clearance was not proportional to the degree of modification. 26992607 0 46 theme IgG 41:43 arg1 clearance 54:62 IgG antibody clearance 41:62 IgG antibody clearance 41:62 Effect of high mannose glycan pairing on IgG antibody clearance. 26992607 5 47 theme HM 734:735 arg1 glycans 737:743 HM glycans 734:743 HM glycans 734:743 Traditional analytical methods, which are used to measure glycans in such studies, do not determine the number of HM glycans per antibody. 26992607 4 48 theme mannose 401:407 arg1 forms 409:413 high mannose forms 396:413 high mannose forms 396:413 Previous studies showing that high mannose forms result in faster mAb clearance in humans were incapable of differentiating the impact of symmetrically vs. asymmetrically paired HM forms, and, therefore, the effect of pairing on clearance was not clear. 26992607 6 49 from clearance 1010:1018 arg1 humans 1023:1028 humans 1023:1028 humans 1023:1028 With a sensitive method designed to measure HM pairing, we followed the levels of symmetrically and asymmetrically paired HM on antibodies in human pharmacokinetic serum samples to determine the impact of Fc HM glycan pairing on therapeutic human IgG clearance in humans. 26992607 1 50 contain contain 80:86 arg2 glycans 97:103 N-linked glycans 88:103 N-linked glycans 88:103 IgG antibodies contain N-linked glycans on the Fc portion of each heavy chain. 26992607 1 50 contain contain 80:86 arg1 portion 115:121 the Fc portion 108:121 the Fc portion of each heavy chain 108:141 IgG antibodies contain N-linked glycans on the Fc portion of each heavy chain. 26992607 1 50 contain contain 80:86 arg2 antibodies 69:78 IgG antibodies 65:78 IgG antibodies 65:78 IgG antibodies contain N-linked glycans on the Fc portion of each heavy chain. 26992607 1 50 contain contain 80:86 arg1 antibodies 69:78 IgG antibodies 65:78 IgG antibodies 65:78 IgG antibodies contain N-linked glycans on the Fc portion of each heavy chain. 26992607 4 51 theme Previous 366:373 arg1 studies 375:381 Previous studies 366:381 Previous studies 366:381 Previous studies showing that high mannose forms result in faster mAb clearance in humans were incapable of differentiating the impact of symmetrically vs. asymmetrically paired HM forms, and, therefore, the effect of pairing on clearance was not clear. 26992607 2 52 theme heavy 215:219 arg1 chain 221:225 the other heavy chain 205:225 the other heavy chain (symmetrical pairing) 205:247 The glycan on one heavy chain can either match the glycan on the other heavy chain (symmetrical pairing) or be different (asymmetrical pairing). 26992607 2 52 theme heavy 215:219 arg1 pairing 240:246 symmetrical pairing 228:246 symmetrical pairing 228:246 The glycan on one heavy chain can either match the glycan on the other heavy chain (symmetrical pairing) or be different (asymmetrical pairing). 26992607 1 53 theme Fc 112:113 arg1 portion 115:121 the Fc portion 108:121 the Fc portion of each heavy chain 108:141 IgG antibodies contain N-linked glycans on the Fc portion of each heavy chain. 26992607 5 54 theme Traditional 620:630 arg1 methods 643:649 Traditional analytical methods 620:649 Traditional analytical methods 620:649 Traditional analytical methods, which are used to measure glycans in such studies, do not determine the number of HM glycans per antibody. 26992607 2 55 theme heavy 162:166 arg1 chain 168:172 one heavy chain 158:172 one heavy chain 158:172 The glycan on one heavy chain can either match the glycan on the other heavy chain (symmetrical pairing) or be different (asymmetrical pairing). 26992607 2 56 theme other 209:213 arg1 chain 221:225 the other heavy chain 205:225 the other heavy chain (symmetrical pairing) 205:247 The glycan on one heavy chain can either match the glycan on the other heavy chain (symmetrical pairing) or be different (asymmetrical pairing). 26992607 2 56 theme other 209:213 arg1 pairing 240:246 symmetrical pairing 228:246 symmetrical pairing 228:246 The glycan on one heavy chain can either match the glycan on the other heavy chain (symmetrical pairing) or be different (asymmetrical pairing). 26992607 8 57 theme therapeutic 1203:1213 arg1 antibodies 1215:1224 therapeutic antibodies 1203:1224 therapeutic antibodies 1203:1224 Since both forms can exist on therapeutic antibodies and the ratio can differ between products, measuring their relative levels is necessary to properly estimate effects on clearance. 26992607 2 58 theme asymmetrical 266:277 arg1 pairing 279:285 asymmetrical pairing 266:285 asymmetrical pairing 266:285 The glycan on one heavy chain can either match the glycan on the other heavy chain (symmetrical pairing) or be different (asymmetrical pairing). 26992607 1 59 link N-linked 88:95 arg1 glycans 97:103 N-linked glycans 88:103 N-linked glycans 88:103 IgG antibodies contain N-linked glycans on the Fc portion of each heavy chain. 26992607 6 60 theme IgG 1006:1008 arg1 clearance 1010:1018 therapeutic human IgG clearance 988:1018 therapeutic human IgG clearance in humans 988:1028 With a sensitive method designed to measure HM pairing, we followed the levels of symmetrically and asymmetrically paired HM on antibodies in human pharmacokinetic serum samples to determine the impact of Fc HM glycan pairing on therapeutic human IgG clearance in humans. 26992607 6 61 theme glycan 970:975 arg1 pairing 977:983 Fc HM glycan pairing 964:983 Fc HM glycan pairing 964:983 With a sensitive method designed to measure HM pairing, we followed the levels of symmetrically and asymmetrically paired HM on antibodies in human pharmacokinetic serum samples to determine the impact of Fc HM glycan pairing on therapeutic human IgG clearance in humans. 26992607 6 62 theme serum 923:927 arg1 samples 929:935 human pharmacokinetic serum samples 901:935 human pharmacokinetic serum samples 901:935 With a sensitive method designed to measure HM pairing, we followed the levels of symmetrically and asymmetrically paired HM on antibodies in human pharmacokinetic serum samples to determine the impact of Fc HM glycan pairing on therapeutic human IgG clearance in humans. 26992607 0 63 theme antibody 45:52 arg1 clearance 54:62 IgG antibody clearance 41:62 IgG antibody clearance 41:62 Effect of high mannose glycan pairing on IgG antibody clearance. 26992607 3 64 theme effector 316:323 arg1 functions 325:333 effector functions 316:333 effector functions 316:333 These Fc glycans influence effector functions and can alter clearance rates. 26992607 6 65 theme human 1000:1004 arg1 clearance 1010:1018 therapeutic human IgG clearance 988:1018 therapeutic human IgG clearance in humans 988:1028 With a sensitive method designed to measure HM pairing, we followed the levels of symmetrically and asymmetrically paired HM on antibodies in human pharmacokinetic serum samples to determine the impact of Fc HM glycan pairing on therapeutic human IgG clearance in humans. 26992607 6 66 theme pharmacokinetic 907:921 arg1 samples 929:935 human pharmacokinetic serum samples 901:935 human pharmacokinetic serum samples 901:935 With a sensitive method designed to measure HM pairing, we followed the levels of symmetrically and asymmetrically paired HM on antibodies in human pharmacokinetic serum samples to determine the impact of Fc HM glycan pairing on therapeutic human IgG clearance in humans. 25293377 3 0 from role 390:393 arg1 stability 422:430 stability 422:430 stability 422:430 Here we have studied the role(s) of glycosylation in the stability, trafficking and vacuolar protein transport of AtVSR1 in Arabidopsis protoplasts. 25293377 3 0 from role 390:393 arg1 transport 466:474 vacuolar protein transport 449:474 vacuolar protein transport 449:474 Here we have studied the role(s) of glycosylation in the stability, trafficking and vacuolar protein transport of AtVSR1 in Arabidopsis protoplasts. 25293377 3 0 from role 390:393 arg1 trafficking 433:443 trafficking 433:443 trafficking 433:443 Here we have studied the role(s) of glycosylation in the stability, trafficking and vacuolar protein transport of AtVSR1 in Arabidopsis protoplasts. 25293377 4 1 theme factor 663:668 arg1 domain 677:682 the C-terminal epidermal growth factor repeat domain 631:682 the C-terminal epidermal growth factor repeat domain 631:682 AtVSR1 harbors three complex-type N-glycans, which are located in the N-terminal 'PA domain', the central region and the C-terminal epidermal growth factor repeat domain, respectively. 25293377 2 2 theme modification 335:346 arg1 significance 312:323 the functional significance 297:323 the functional significance of such a modification 297:346 The VSRs are post-translationally modified by the attachment of N-glycans, but the functional significance of such a modification remains unknown. 25293377 5 3 gly N-glycosylation 857:871 arg1 cargo 958:962 cargo 958:962 cargo 958:962 We have demonstrated that: (i) the N-glycans do not affect the targeting of AtVSR1 to pre-vacuolar compartments (PVCs) and its vacuolar degradation; and (ii) N-glycosylation alters the binding affinity of AtVSR1 to cargo proteins and affects the transport of cargo into the vacuole. 25293377 3 4 dep stability 422:430 arg1 the 418:420 the 418:420 the 418:420 Here we have studied the role(s) of glycosylation in the stability, trafficking and vacuolar protein transport of AtVSR1 in Arabidopsis protoplasts. 25293377 4 5 theme C-terminal 635:644 arg1 domain 677:682 the C-terminal epidermal growth factor repeat domain 631:682 the C-terminal epidermal growth factor repeat domain 631:682 AtVSR1 harbors three complex-type N-glycans, which are located in the N-terminal 'PA domain', the central region and the C-terminal epidermal growth factor repeat domain, respectively. 25293377 2 6 theme N-glycans 282:290 arg1 attachment 268:277 the attachment 264:277 the attachment of N-glycans 264:290 The VSRs are post-translationally modified by the attachment of N-glycans, but the functional significance of such a modification remains unknown. 25293377 5 7 theme cargo 914:918 arg1 proteins 920:927 cargo proteins 914:927 cargo proteins 914:927 We have demonstrated that: (i) the N-glycans do not affect the targeting of AtVSR1 to pre-vacuolar compartments (PVCs) and its vacuolar degradation; and (ii) N-glycosylation alters the binding affinity of AtVSR1 to cargo proteins and affects the transport of cargo into the vacuole. 25293377 4 8 from located 569:575 arg1 region 620:625 the central region 608:625 the central region 608:625 AtVSR1 harbors three complex-type N-glycans, which are located in the N-terminal 'PA domain', the central region and the C-terminal epidermal growth factor repeat domain, respectively. 25293377 4 8 from located 569:575 arg1 domain 599:604 the N-terminal 'PA domain' 580:605 the N-terminal 'PA domain' 580:605 AtVSR1 harbors three complex-type N-glycans, which are located in the N-terminal 'PA domain', the central region and the C-terminal epidermal growth factor repeat domain, respectively. 25293377 4 8 from located 569:575 arg1 domain 677:682 the C-terminal epidermal growth factor repeat domain 631:682 the C-terminal epidermal growth factor repeat domain 631:682 AtVSR1 harbors three complex-type N-glycans, which are located in the N-terminal 'PA domain', the central region and the C-terminal epidermal growth factor repeat domain, respectively. 25293377 5 9 dep affect 751:756 arg1 i 727:727 i 727:727 i 727:727 We have demonstrated that: (i) the N-glycans do not affect the targeting of AtVSR1 to pre-vacuolar compartments (PVCs) and its vacuolar degradation; and (ii) N-glycosylation alters the binding affinity of AtVSR1 to cargo proteins and affects the transport of cargo into the vacuole. 25293377 5 10 theme vacuolar 826:833 arg1 degradation 835:845 its vacuolar degradation 822:845 its vacuolar degradation 822:845 We have demonstrated that: (i) the N-glycans do not affect the targeting of AtVSR1 to pre-vacuolar compartments (PVCs) and its vacuolar degradation; and (ii) N-glycosylation alters the binding affinity of AtVSR1 to cargo proteins and affects the transport of cargo into the vacuole. 25293377 6 11 theme critical 1023:1030 arg1 role 1032:1035 a critical role 1021:1035 a critical role 1021:1035 Hence, N-glycosylation of AtVSR1 plays a critical role in its function as a VSR in plants. 25293377 4 12 theme growth 656:661 arg1 domain 677:682 the C-terminal epidermal growth factor repeat domain 631:682 the C-terminal epidermal growth factor repeat domain 631:682 AtVSR1 harbors three complex-type N-glycans, which are located in the N-terminal 'PA domain', the central region and the C-terminal epidermal growth factor repeat domain, respectively. 25293377 6 13 theme AtVSR1 1008:1013 arg1 N-glycosylation 989:1003 N-glycosylation 989:1003 N-glycosylation of AtVSR1 989:1013 Hence, N-glycosylation of AtVSR1 plays a critical role in its function as a VSR in plants. 25293377 0 14 link N-linked 0:7 arg1 glycosylation 9:21 N-linked glycosylation 0:21 N-linked glycosylation of AtVSR1 0:31 N-linked glycosylation of AtVSR1 is important for vacuolar protein sorting in Arabidopsis. 25293377 3 15 theme glycosylation 401:413 arg1 role 390:393 the role 386:393 the role(s) of glycosylation in the stability, trafficking and vacuolar protein transport of AtVSR1 in Arabidopsis protoplasts 386:511 Here we have studied the role(s) of glycosylation in the stability, trafficking and vacuolar protein transport of AtVSR1 in Arabidopsis protoplasts. 25293377 3 15 theme glycosylation 401:413 arg1 s 395:395 s 395:395 s 395:395 Here we have studied the role(s) of glycosylation in the stability, trafficking and vacuolar protein transport of AtVSR1 in Arabidopsis protoplasts. 25293377 5 16 theme AtVSR1 904:909 arg1 affinity 892:899 the binding affinity 880:899 the binding affinity of AtVSR1 to cargo proteins 880:927 We have demonstrated that: (i) the N-glycans do not affect the targeting of AtVSR1 to pre-vacuolar compartments (PVCs) and its vacuolar degradation; and (ii) N-glycosylation alters the binding affinity of AtVSR1 to cargo proteins and affects the transport of cargo into the vacuole. 25293377 4 17 from region 620:625 arg1 located 569:575 located 569:575 located 569:575 AtVSR1 harbors three complex-type N-glycans, which are located in the N-terminal 'PA domain', the central region and the C-terminal epidermal growth factor repeat domain, respectively. 25293377 1 18 theme soluble 163:169 arg1 proteins 171:178 soluble proteins 163:178 soluble proteins 163:178 Vacuolar sorting receptors (VSRs) in Arabidopsis mediate the sorting of soluble proteins to vacuoles in the secretory pathway. 25293377 2 19 theme functional 301:310 arg1 significance 312:323 the functional significance 297:323 the functional significance of such a modification 297:346 The VSRs are post-translationally modified by the attachment of N-glycans, but the functional significance of such a modification remains unknown. 25293377 1 20 theme proteins 171:178 arg1 sorting 152:158 the sorting 148:158 the sorting of soluble proteins to vacuoles in the secretory pathway 148:215 Vacuolar sorting receptors (VSRs) in Arabidopsis mediate the sorting of soluble proteins to vacuoles in the secretory pathway. 25293377 0 21 theme N-linked 0:7 arg1 glycosylation 9:21 N-linked glycosylation 0:21 N-linked glycosylation of AtVSR1 0:31 N-linked glycosylation of AtVSR1 is important for vacuolar protein sorting in Arabidopsis. 25293377 4 22 theme complex-type 535:546 arg1 N-glycans 548:556 three complex-type N-glycans 529:556 three complex-type N-glycans 529:556 AtVSR1 harbors three complex-type N-glycans, which are located in the N-terminal 'PA domain', the central region and the C-terminal epidermal growth factor repeat domain, respectively. 25293377 1 23 theme Vacuolar 91:98 arg1 VSRs 119:122 VSRs 119:122 VSRs 119:122 Vacuolar sorting receptors (VSRs) in Arabidopsis mediate the sorting of soluble proteins to vacuoles in the secretory pathway. 25293377 1 23 theme Vacuolar 91:98 arg1 receptors 108:116 Vacuolar sorting receptors 91:116 Vacuolar sorting receptors (VSRs) in Arabidopsis 91:138 Vacuolar sorting receptors (VSRs) in Arabidopsis mediate the sorting of soluble proteins to vacuoles in the secretory pathway. 25293377 0 24 theme AtVSR1 26:31 arg1 glycosylation 9:21 N-linked glycosylation 0:21 N-linked glycosylation of AtVSR1 0:31 N-linked glycosylation of AtVSR1 is important for vacuolar protein sorting in Arabidopsis. 25293377 3 25 from transport 466:474 arg1 protoplasts 501:511 Arabidopsis protoplasts 489:511 Arabidopsis protoplasts 489:511 Here we have studied the role(s) of glycosylation in the stability, trafficking and vacuolar protein transport of AtVSR1 in Arabidopsis protoplasts. 25293377 1 26 theme sorting 100:106 arg1 VSRs 119:122 VSRs 119:122 VSRs 119:122 Vacuolar sorting receptors (VSRs) in Arabidopsis mediate the sorting of soluble proteins to vacuoles in the secretory pathway. 25293377 1 26 theme sorting 100:106 arg1 receptors 108:116 Vacuolar sorting receptors 91:116 Vacuolar sorting receptors (VSRs) in Arabidopsis 91:138 Vacuolar sorting receptors (VSRs) in Arabidopsis mediate the sorting of soluble proteins to vacuoles in the secretory pathway. 25293377 5 27 theme binding 884:890 arg1 affinity 892:899 the binding affinity 880:899 the binding affinity of AtVSR1 to cargo proteins 880:927 We have demonstrated that: (i) the N-glycans do not affect the targeting of AtVSR1 to pre-vacuolar compartments (PVCs) and its vacuolar degradation; and (ii) N-glycosylation alters the binding affinity of AtVSR1 to cargo proteins and affects the transport of cargo into the vacuole. 25293377 3 28 theme AtVSR1 479:484 arg1 stability 422:430 stability 422:430 stability 422:430 Here we have studied the role(s) of glycosylation in the stability, trafficking and vacuolar protein transport of AtVSR1 in Arabidopsis protoplasts. 25293377 3 28 theme AtVSR1 479:484 arg1 transport 466:474 vacuolar protein transport 449:474 vacuolar protein transport 449:474 Here we have studied the role(s) of glycosylation in the stability, trafficking and vacuolar protein transport of AtVSR1 in Arabidopsis protoplasts. 25293377 3 28 theme AtVSR1 479:484 arg1 trafficking 433:443 trafficking 433:443 trafficking 433:443 Here we have studied the role(s) of glycosylation in the stability, trafficking and vacuolar protein transport of AtVSR1 in Arabidopsis protoplasts. 25293377 6 29 from VSR 1058:1060 arg1 plants 1065:1070 plants 1065:1070 plants 1065:1070 Hence, N-glycosylation of AtVSR1 plays a critical role in its function as a VSR in plants. 25293377 5 30 theme AtVSR1 775:780 arg1 targeting 762:770 the targeting 758:770 the targeting of AtVSR1 to pre-vacuolar compartments (PVCs) and its vacuolar degradation 758:845 We have demonstrated that: (i) the N-glycans do not affect the targeting of AtVSR1 to pre-vacuolar compartments (PVCs) and its vacuolar degradation; and (ii) N-glycosylation alters the binding affinity of AtVSR1 to cargo proteins and affects the transport of cargo into the vacuole. 25293377 4 31 from domain 599:604 arg1 located 569:575 located 569:575 located 569:575 AtVSR1 harbors three complex-type N-glycans, which are located in the N-terminal 'PA domain', the central region and the C-terminal epidermal growth factor repeat domain, respectively. 25293377 0 32 from sorting 67:73 arg1 Arabidopsis 78:88 Arabidopsis 78:88 Arabidopsis 78:88 N-linked glycosylation of AtVSR1 is important for vacuolar protein sorting in Arabidopsis. 25293377 0 33 gly glycosylation 9:21 arg1 protein 59:65 vacuolar protein sorting 50:73 vacuolar protein sorting in Arabidopsis 50:88 N-linked glycosylation of AtVSR1 is important for vacuolar protein sorting in Arabidopsis. 25293377 0 33 gly glycosylation 9:21 arg1 AtVSR1 26:31 AtVSR1 26:31 AtVSR1 26:31 N-linked glycosylation of AtVSR1 is important for vacuolar protein sorting in Arabidopsis. 25293377 1 34 theme secretory 199:207 arg1 pathway 209:215 the secretory pathway 195:215 the secretory pathway 195:215 Vacuolar sorting receptors (VSRs) in Arabidopsis mediate the sorting of soluble proteins to vacuoles in the secretory pathway. 25293377 0 35 theme vacuolar 50:57 arg1 sorting 67:73 vacuolar protein sorting 50:73 vacuolar protein sorting in Arabidopsis 50:88 N-linked glycosylation of AtVSR1 is important for vacuolar protein sorting in Arabidopsis. 25293377 3 36 from stability 422:430 arg1 protoplasts 501:511 Arabidopsis protoplasts 489:511 Arabidopsis protoplasts 489:511 Here we have studied the role(s) of glycosylation in the stability, trafficking and vacuolar protein transport of AtVSR1 in Arabidopsis protoplasts. 25293377 3 37 theme protein 458:464 arg1 transport 466:474 vacuolar protein transport 449:474 vacuolar protein transport 449:474 Here we have studied the role(s) of glycosylation in the stability, trafficking and vacuolar protein transport of AtVSR1 in Arabidopsis protoplasts. 25293377 5 38 dep N-glycosylation 857:871 arg1 ii 853:854 ii 853:854 ii 853:854 We have demonstrated that: (i) the N-glycans do not affect the targeting of AtVSR1 to pre-vacuolar compartments (PVCs) and its vacuolar degradation; and (ii) N-glycosylation alters the binding affinity of AtVSR1 to cargo proteins and affects the transport of cargo into the vacuole. 25293377 6 39 gly N-glycosylation 989:1003 arg1 AtVSR1 1008:1013 AtVSR1 1008:1013 AtVSR1 1008:1013 Hence, N-glycosylation of AtVSR1 plays a critical role in its function as a VSR in plants. 25293377 5 40 theme cargo 958:962 arg1 transport 945:953 the transport 941:953 the transport of cargo into the vacuole 941:979 We have demonstrated that: (i) the N-glycans do not affect the targeting of AtVSR1 to pre-vacuolar compartments (PVCs) and its vacuolar degradation; and (ii) N-glycosylation alters the binding affinity of AtVSR1 to cargo proteins and affects the transport of cargo into the vacuole. 25293377 1 41 from vacuoles 183:190 arg1 pathway 209:215 the secretory pathway 195:215 the secretory pathway 195:215 Vacuolar sorting receptors (VSRs) in Arabidopsis mediate the sorting of soluble proteins to vacuoles in the secretory pathway. 25293377 4 42 theme repeat 670:675 arg1 domain 677:682 the C-terminal epidermal growth factor repeat domain 631:682 the C-terminal epidermal growth factor repeat domain 631:682 AtVSR1 harbors three complex-type N-glycans, which are located in the N-terminal 'PA domain', the central region and the C-terminal epidermal growth factor repeat domain, respectively. 25293377 3 43 from trafficking 433:443 arg1 protoplasts 501:511 Arabidopsis protoplasts 489:511 Arabidopsis protoplasts 489:511 Here we have studied the role(s) of glycosylation in the stability, trafficking and vacuolar protein transport of AtVSR1 in Arabidopsis protoplasts. 25293377 1 44 from receptors 108:116 arg1 Arabidopsis 128:138 Arabidopsis 128:138 Arabidopsis 128:138 Vacuolar sorting receptors (VSRs) in Arabidopsis mediate the sorting of soluble proteins to vacuoles in the secretory pathway. 25293377 4 45 theme N-terminal 584:593 arg1 domain 599:604 the N-terminal 'PA domain' 580:605 the N-terminal 'PA domain' 580:605 AtVSR1 harbors three complex-type N-glycans, which are located in the N-terminal 'PA domain', the central region and the C-terminal epidermal growth factor repeat domain, respectively. 25293377 3 46 gly glycosylation 401:413 arg1 protein 458:464 vacuolar protein transport 449:474 vacuolar protein transport 449:474 Here we have studied the role(s) of glycosylation in the stability, trafficking and vacuolar protein transport of AtVSR1 in Arabidopsis protoplasts. 25293377 3 46 gly glycosylation 401:413 arg1 AtVSR1 479:484 AtVSR1 479:484 AtVSR1 479:484 Here we have studied the role(s) of glycosylation in the stability, trafficking and vacuolar protein transport of AtVSR1 in Arabidopsis protoplasts. 25293377 3 47 theme vacuolar 449:456 arg1 transport 466:474 vacuolar protein transport 449:474 vacuolar protein transport 449:474 Here we have studied the role(s) of glycosylation in the stability, trafficking and vacuolar protein transport of AtVSR1 in Arabidopsis protoplasts. 25293377 4 48 from domain 677:682 arg1 located 569:575 located 569:575 located 569:575 AtVSR1 harbors three complex-type N-glycans, which are located in the N-terminal 'PA domain', the central region and the C-terminal epidermal growth factor repeat domain, respectively. 25293377 5 49 theme pre-vacuolar 785:796 arg1 PVCs 812:815 PVCs 812:815 PVCs 812:815 We have demonstrated that: (i) the N-glycans do not affect the targeting of AtVSR1 to pre-vacuolar compartments (PVCs) and its vacuolar degradation; and (ii) N-glycosylation alters the binding affinity of AtVSR1 to cargo proteins and affects the transport of cargo into the vacuole. 25293377 5 49 theme pre-vacuolar 785:796 arg1 compartments 798:809 pre-vacuolar compartments 785:809 pre-vacuolar compartments (PVCs) 785:816 We have demonstrated that: (i) the N-glycans do not affect the targeting of AtVSR1 to pre-vacuolar compartments (PVCs) and its vacuolar degradation; and (ii) N-glycosylation alters the binding affinity of AtVSR1 to cargo proteins and affects the transport of cargo into the vacuole. 25293377 4 50 located located 569:575 arg1 region 620:625 the central region 608:625 the central region 608:625 AtVSR1 harbors three complex-type N-glycans, which are located in the N-terminal 'PA domain', the central region and the C-terminal epidermal growth factor repeat domain, respectively. 25293377 4 50 located located 569:575 arg1 domain 599:604 the N-terminal 'PA domain' 580:605 the N-terminal 'PA domain' 580:605 AtVSR1 harbors three complex-type N-glycans, which are located in the N-terminal 'PA domain', the central region and the C-terminal epidermal growth factor repeat domain, respectively. 25293377 4 50 located located 569:575 arg2 N-glycans 548:556 three complex-type N-glycans 529:556 three complex-type N-glycans 529:556 AtVSR1 harbors three complex-type N-glycans, which are located in the N-terminal 'PA domain', the central region and the C-terminal epidermal growth factor repeat domain, respectively. 25293377 4 50 located located 569:575 arg1 domain 677:682 the C-terminal epidermal growth factor repeat domain 631:682 the C-terminal epidermal growth factor repeat domain 631:682 AtVSR1 harbors three complex-type N-glycans, which are located in the N-terminal 'PA domain', the central region and the C-terminal epidermal growth factor repeat domain, respectively. 25293377 4 51 theme epidermal 646:654 arg1 domain 677:682 the C-terminal epidermal growth factor repeat domain 631:682 the C-terminal epidermal growth factor repeat domain 631:682 AtVSR1 harbors three complex-type N-glycans, which are located in the N-terminal 'PA domain', the central region and the C-terminal epidermal growth factor repeat domain, respectively. 25293377 4 52 theme central 612:618 arg1 region 620:625 the central region 608:625 the central region 608:625 AtVSR1 harbors three complex-type N-glycans, which are located in the N-terminal 'PA domain', the central region and the C-terminal epidermal growth factor repeat domain, respectively. 25293377 4 53 theme PA 596:597 arg1 domain 599:604 the N-terminal 'PA domain' 580:605 the N-terminal 'PA domain' 580:605 AtVSR1 harbors three complex-type N-glycans, which are located in the N-terminal 'PA domain', the central region and the C-terminal epidermal growth factor repeat domain, respectively. 25293377 0 54 theme protein 59:65 arg1 sorting 67:73 vacuolar protein sorting 50:73 vacuolar protein sorting in Arabidopsis 50:88 N-linked glycosylation of AtVSR1 is important for vacuolar protein sorting in Arabidopsis. 25293377 2 55 mod modified 252:259 arg1 VSRs 222:225 The VSRs 218:225 The VSRs 218:225 The VSRs are post-translationally modified by the attachment of N-glycans, but the functional significance of such a modification remains unknown. 25293377 2 55 mod modified 252:259 arg3 attachment 268:277 the attachment 264:277 the attachment of N-glycans 264:290 The VSRs are post-translationally modified by the attachment of N-glycans, but the functional significance of such a modification remains unknown. 25293377 3 56 theme Arabidopsis 489:499 arg1 protoplasts 501:511 Arabidopsis protoplasts 489:511 Arabidopsis protoplasts 489:511 Here we have studied the role(s) of glycosylation in the stability, trafficking and vacuolar protein transport of AtVSR1 in Arabidopsis protoplasts. 24660168 4 0 theme cDNA 639:642 arg1 Expression 625:634 Expression 625:634 Expression of cDNA in Pichia pastoris 625:661 Expression of cDNA in Pichia pastoris resulted in the secretion of aLAM activity into the culture medium. 24660168 1 1 theme biosynthesis 240:251 arg1 process 292:298 the biosynthesis and turnover of N-linked glycoproteins process 236:298 the biosynthesis and turnover of N-linked glycoproteins process 236:298 Lysosomal α-Mannosidase (LAM) belongs to the glycoside hydrolyzing enzymes family 38 and is involved in the biosynthesis and turnover of N-linked glycoproteins process. 24660168 0 2 theme site 88:91 arg1 characterization 10:25 Molecular characterization 0:25 Molecular characterization of Capra hircus lysosomal α-mannosidase and potential mutant site for the therapy of locoweed poisoning. 0:130 Molecular characterization of Capra hircus lysosomal α-mannosidase and potential mutant site for the therapy of locoweed poisoning. 24660168 6 3 from sites 946:950 arg1 sites 987:991 the potential mutant sites 966:991 the potential mutant sites for the resistance to SW 966:1016 By homology modeling, molecular docking and mutant analysis, we obtained the probable binding modes of SW at the allosteric sites of chLAM, and the potential mutant sites for the resistance to SW. 24660168 6 3 from sites 946:950 arg1 SW 925:926 SW 925:926 SW at the allosteric sites of chLAM 925:959 By homology modeling, molecular docking and mutant analysis, we obtained the probable binding modes of SW at the allosteric sites of chLAM, and the potential mutant sites for the resistance to SW. 24660168 6 3 from sites 946:950 arg1 modes 916:920 the probable binding modes 895:920 the probable binding modes of SW at the allosteric sites of chLAM 895:959 By homology modeling, molecular docking and mutant analysis, we obtained the probable binding modes of SW at the allosteric sites of chLAM, and the potential mutant sites for the resistance to SW. 24660168 4 4 from Expression 625:634 arg1 pastoris 654:661 Pichia pastoris 647:661 Pichia pastoris 647:661 Expression of cDNA in Pichia pastoris resulted in the secretion of aLAM activity into the culture medium. 24660168 7 5 theme W/G 1055:1057 arg1 chLAM 1075:1079 A28 W/G, D58 Y/G mutant chLAM 1051:1079 chLAM 1075:1079 Prediction of SW sensitivity to A28 W/G, D58 Y/G mutant chLAM is lower than wild type chLAM. 24660168 8 6 theme potential 1235:1243 arg1 strategy 1245:1252 a potential strategy 1233:1252 a potential strategy for a novel therapy for locoweed poisoning 1233:1295 The obtained results lead to a better understanding of not only interactions between substrate/SW and chLAM, but also of a potential strategy for a novel therapy for locoweed poisoning. 24660168 6 7 from modes 916:920 arg1 sites 946:950 the allosteric sites 931:950 the allosteric sites of chLAM 931:959 By homology modeling, molecular docking and mutant analysis, we obtained the probable binding modes of SW at the allosteric sites of chLAM, and the potential mutant sites for the resistance to SW. 24660168 6 7 from modes 916:920 arg1 chLAM 955:959 chLAM 955:959 chLAM 955:959 By homology modeling, molecular docking and mutant analysis, we obtained the probable binding modes of SW at the allosteric sites of chLAM, and the potential mutant sites for the resistance to SW. 24660168 3 8 theme protein 499:505 arg1 conservation 516:527 protein sequence conservation 499:527 protein sequence conservation between LAM from Bos taurus and Homo sapiens 499:572 Based on regions of protein sequence conservation between LAM from Bos taurus and Homo sapiens, we cloned cDNA encoding Capra hircus LAM (chLAM). 24660168 1 9 theme turnover 257:264 arg1 process 292:298 the biosynthesis and turnover of N-linked glycoproteins process 236:298 the biosynthesis and turnover of N-linked glycoproteins process 236:298 Lysosomal α-Mannosidase (LAM) belongs to the glycoside hydrolyzing enzymes family 38 and is involved in the biosynthesis and turnover of N-linked glycoproteins process. 24660168 7 10 theme type 1100:1103 arg1 chLAM 1105:1109 wild type chLAM 1095:1109 wild type chLAM 1095:1109 Prediction of SW sensitivity to A28 W/G, D58 Y/G mutant chLAM is lower than wild type chLAM. 24660168 4 11 theme aLAM 692:695 arg1 activity 697:704 aLAM activity 692:704 aLAM activity 692:704 Expression of cDNA in Pichia pastoris resulted in the secretion of aLAM activity into the culture medium. 24660168 3 12 theme sequence 507:514 arg1 conservation 516:527 protein sequence conservation 499:527 protein sequence conservation between LAM from Bos taurus and Homo sapiens 499:572 Based on regions of protein sequence conservation between LAM from Bos taurus and Homo sapiens, we cloned cDNA encoding Capra hircus LAM (chLAM). 24660168 3 13 from sapiens 566:572 arg1 LAM 537:539 LAM 537:539 LAM from Bos taurus and Homo sapiens 537:572 Based on regions of protein sequence conservation between LAM from Bos taurus and Homo sapiens, we cloned cDNA encoding Capra hircus LAM (chLAM). 24660168 0 14 theme locoweed 112:119 arg1 poisoning 121:129 locoweed poisoning 112:129 locoweed poisoning 112:129 Molecular characterization of Capra hircus lysosomal α-mannosidase and potential mutant site for the therapy of locoweed poisoning. 24660168 6 15 theme chLAM 955:959 arg1 sites 946:950 the allosteric sites 931:950 the allosteric sites of chLAM 931:959 By homology modeling, molecular docking and mutant analysis, we obtained the probable binding modes of SW at the allosteric sites of chLAM, and the potential mutant sites for the resistance to SW. 24660168 6 15 theme chLAM 955:959 arg1 chLAM 955:959 chLAM 955:959 chLAM 955:959 By homology modeling, molecular docking and mutant analysis, we obtained the probable binding modes of SW at the allosteric sites of chLAM, and the potential mutant sites for the resistance to SW. 24660168 2 16 theme poisoning 375:383 arg1 Locoweeds 301:309 Locoweeds 301:309 Locoweeds 301:309 Locoweeds, which contain swainsonine (SW) that inhibits LAM, are the main poisoning plants in many regions of the world, and thereby resulting in animal poisoning or even death. 24660168 2 16 theme poisoning 375:383 arg1 plants 385:390 the main poisoning plants 366:390 the main poisoning plants 366:390 Locoweeds, which contain swainsonine (SW) that inhibits LAM, are the main poisoning plants in many regions of the world, and thereby resulting in animal poisoning or even death. 24660168 7 17 theme A28 1051:1053 arg1 chLAM 1075:1079 A28 W/G, D58 Y/G mutant chLAM 1051:1079 chLAM 1075:1079 Prediction of SW sensitivity to A28 W/G, D58 Y/G mutant chLAM is lower than wild type chLAM. 24660168 8 18 theme better 1143:1148 arg1 understanding 1150:1162 a better understanding 1141:1162 a better understanding of not only interactions between substrate/SW and chLAM, but also of a potential strategy for a novel therapy for locoweed poisoning 1141:1295 The obtained results lead to a better understanding of not only interactions between substrate/SW and chLAM, but also of a potential strategy for a novel therapy for locoweed poisoning. 24660168 2 19 theme world 415:419 arg1 regions 400:406 many regions 395:406 many regions of the world 395:419 Locoweeds, which contain swainsonine (SW) that inhibits LAM, are the main poisoning plants in many regions of the world, and thereby resulting in animal poisoning or even death. 24660168 2 20 theme main 370:373 arg1 Locoweeds 301:309 Locoweeds 301:309 Locoweeds 301:309 Locoweeds, which contain swainsonine (SW) that inhibits LAM, are the main poisoning plants in many regions of the world, and thereby resulting in animal poisoning or even death. 24660168 2 20 theme main 370:373 arg1 plants 385:390 the main poisoning plants 366:390 the main poisoning plants 366:390 Locoweeds, which contain swainsonine (SW) that inhibits LAM, are the main poisoning plants in many regions of the world, and thereby resulting in animal poisoning or even death. 24660168 5 21 theme recombinant 735:745 arg1 chLAM 747:751 The recombinant chLAM 731:751 The recombinant chLAM 731:751 The recombinant chLAM was activated 1.6 and 1.2-fold with Zn(2+) and Ca(2+), respectively. 24660168 5 21 theme recombinant 735:745 arg1 1.6 767:769 1.6 767:769 1.6 767:769 The recombinant chLAM was activated 1.6 and 1.2-fold with Zn(2+) and Ca(2+), respectively. 24660168 2 22 theme animal 447:452 arg1 poisoning 454:462 animal poisoning 447:462 animal poisoning 447:462 Locoweeds, which contain swainsonine (SW) that inhibits LAM, are the main poisoning plants in many regions of the world, and thereby resulting in animal poisoning or even death. 24660168 7 23 theme Y/G 1064:1066 arg1 chLAM 1075:1079 A28 W/G, D58 Y/G mutant chLAM 1051:1079 chLAM 1075:1079 Prediction of SW sensitivity to A28 W/G, D58 Y/G mutant chLAM is lower than wild type chLAM. 24660168 2 24 theme even 467:470 arg1 death 472:476 even death 467:476 even death 467:476 Locoweeds, which contain swainsonine (SW) that inhibits LAM, are the main poisoning plants in many regions of the world, and thereby resulting in animal poisoning or even death. 24660168 1 25 theme glycoside 177:185 arg1 family 207:212 the glycoside hydrolyzing enzymes family 38 173:215 the glycoside hydrolyzing enzymes family 38 173:215 Lysosomal α-Mannosidase (LAM) belongs to the glycoside hydrolyzing enzymes family 38 and is involved in the biosynthesis and turnover of N-linked glycoproteins process. 24660168 0 26 theme Molecular 0:8 arg1 characterization 10:25 Molecular characterization 0:25 Molecular characterization of Capra hircus lysosomal α-mannosidase and potential mutant site for the therapy of locoweed poisoning. 0:130 Molecular characterization of Capra hircus lysosomal α-mannosidase and potential mutant site for the therapy of locoweed poisoning. 24660168 1 27 theme N-linked 269:276 arg1 glycoproteins 278:290 N-linked glycoproteins 269:290 N-linked glycoproteins 269:290 Lysosomal α-Mannosidase (LAM) belongs to the glycoside hydrolyzing enzymes family 38 and is involved in the biosynthesis and turnover of N-linked glycoproteins process. 24660168 3 28 from Bos 546:548 arg1 LAM 537:539 LAM 537:539 LAM from Bos taurus and Homo sapiens 537:572 Based on regions of protein sequence conservation between LAM from Bos taurus and Homo sapiens, we cloned cDNA encoding Capra hircus LAM (chLAM). 24660168 1 29 theme hydrolyzing 187:197 arg1 family 207:212 the glycoside hydrolyzing enzymes family 38 173:215 the glycoside hydrolyzing enzymes family 38 173:215 Lysosomal α-Mannosidase (LAM) belongs to the glycoside hydrolyzing enzymes family 38 and is involved in the biosynthesis and turnover of N-linked glycoproteins process. 24660168 0 30 theme Capra 30:34 arg1 hircus 36:41 Capra hircus lysosomal α-mannosidase and potential mutant site 30:91 hircus 36:41 Molecular characterization of Capra hircus lysosomal α-mannosidase and potential mutant site for the therapy of locoweed poisoning. 24660168 1 31 theme glycoproteins 278:290 arg1 turnover 257:264 turnover 257:264 turnover of N-linked glycoproteins 257:290 Lysosomal α-Mannosidase (LAM) belongs to the glycoside hydrolyzing enzymes family 38 and is involved in the biosynthesis and turnover of N-linked glycoproteins process. 24660168 1 31 theme glycoproteins 278:290 arg1 biosynthesis 240:251 biosynthesis 240:251 biosynthesis 240:251 Lysosomal α-Mannosidase (LAM) belongs to the glycoside hydrolyzing enzymes family 38 and is involved in the biosynthesis and turnover of N-linked glycoproteins process. 24660168 3 32 dep Bos 546:548 arg1 taurus 550:555 Bos taurus 546:555 Bos taurus 546:555 Based on regions of protein sequence conservation between LAM from Bos taurus and Homo sapiens, we cloned cDNA encoding Capra hircus LAM (chLAM). 24660168 3 33 theme conservation 516:527 arg1 regions 488:494 regions 488:494 regions of protein sequence conservation between LAM from Bos taurus and Homo sapiens 488:572 Based on regions of protein sequence conservation between LAM from Bos taurus and Homo sapiens, we cloned cDNA encoding Capra hircus LAM (chLAM). 24660168 1 34 theme enzymes 199:205 arg1 family 207:212 the glycoside hydrolyzing enzymes family 38 173:215 the glycoside hydrolyzing enzymes family 38 173:215 Lysosomal α-Mannosidase (LAM) belongs to the glycoside hydrolyzing enzymes family 38 and is involved in the biosynthesis and turnover of N-linked glycoproteins process. 24660168 0 35 theme poisoning 121:129 arg1 therapy 101:107 the therapy 97:107 the therapy of locoweed poisoning 97:129 Molecular characterization of Capra hircus lysosomal α-mannosidase and potential mutant site for the therapy of locoweed poisoning. 24660168 3 36 theme Capra 599:603 arg1 hircus 605:610 Capra hircus LAM (chLAM) 599:622 Capra hircus LAM (chLAM) 599:622 Based on regions of protein sequence conservation between LAM from Bos taurus and Homo sapiens, we cloned cDNA encoding Capra hircus LAM (chLAM). 24660168 2 37 theme many 395:398 arg1 regions 400:406 many regions 395:406 many regions of the world 395:419 Locoweeds, which contain swainsonine (SW) that inhibits LAM, are the main poisoning plants in many regions of the world, and thereby resulting in animal poisoning or even death. 24660168 0 38 theme lysosomal 43:51 arg1 α-mannosidase 53:65 lysosomal α-mannosidase 43:65 lysosomal α-mannosidase 43:65 Molecular characterization of Capra hircus lysosomal α-mannosidase and potential mutant site for the therapy of locoweed poisoning. 24660168 4 39 theme activity 697:704 arg1 secretion 679:687 the secretion 675:687 the secretion of aLAM activity into the culture medium 675:728 Expression of cDNA in Pichia pastoris resulted in the secretion of aLAM activity into the culture medium. 24660168 7 40 theme sensitivity 1036:1046 arg1 Prediction 1019:1028 Prediction 1019:1028 Prediction of SW sensitivity to A28 W/G, D58 Y/G mutant chLAM 1019:1079 Prediction of SW sensitivity to A28 W/G, D58 Y/G mutant chLAM is lower than wild type chLAM. 24660168 6 41 theme molecular 844:852 arg1 docking 854:860 molecular docking 844:860 molecular docking 844:860 By homology modeling, molecular docking and mutant analysis, we obtained the probable binding modes of SW at the allosteric sites of chLAM, and the potential mutant sites for the resistance to SW. 24660168 6 42 theme allosteric 935:944 arg1 sites 946:950 the allosteric sites 931:950 the allosteric sites of chLAM 931:959 By homology modeling, molecular docking and mutant analysis, we obtained the probable binding modes of SW at the allosteric sites of chLAM, and the potential mutant sites for the resistance to SW. 24660168 6 42 theme allosteric 935:944 arg1 chLAM 955:959 chLAM 955:959 chLAM 955:959 By homology modeling, molecular docking and mutant analysis, we obtained the probable binding modes of SW at the allosteric sites of chLAM, and the potential mutant sites for the resistance to SW. 24660168 6 43 theme SW 925:926 arg1 sites 987:991 the potential mutant sites 966:991 the potential mutant sites for the resistance to SW 966:1016 By homology modeling, molecular docking and mutant analysis, we obtained the probable binding modes of SW at the allosteric sites of chLAM, and the potential mutant sites for the resistance to SW. 24660168 6 43 theme SW 925:926 arg1 SW 925:926 SW 925:926 SW at the allosteric sites of chLAM 925:959 By homology modeling, molecular docking and mutant analysis, we obtained the probable binding modes of SW at the allosteric sites of chLAM, and the potential mutant sites for the resistance to SW. 24660168 6 43 theme SW 925:926 arg1 modes 916:920 the probable binding modes 895:920 the probable binding modes of SW at the allosteric sites of chLAM 895:959 By homology modeling, molecular docking and mutant analysis, we obtained the probable binding modes of SW at the allosteric sites of chLAM, and the potential mutant sites for the resistance to SW. 24660168 0 44 theme hircus 36:41 arg1 characterization 10:25 Molecular characterization 0:25 Molecular characterization of Capra hircus lysosomal α-mannosidase and potential mutant site for the therapy of locoweed poisoning. 0:130 Molecular characterization of Capra hircus lysosomal α-mannosidase and potential mutant site for the therapy of locoweed poisoning. 24660168 7 45 dep chLAM 1075:1079 arg1 D58 1060:1062 A28 W/G, D58 Y/G mutant chLAM 1051:1079 D58 1060:1062 Prediction of SW sensitivity to A28 W/G, D58 Y/G mutant chLAM is lower than wild type chLAM. 24660168 8 46 theme locoweed 1278:1285 arg1 poisoning 1287:1295 locoweed poisoning 1278:1295 locoweed poisoning 1278:1295 The obtained results lead to a better understanding of not only interactions between substrate/SW and chLAM, but also of a potential strategy for a novel therapy for locoweed poisoning. 24660168 3 47 theme Homo 561:564 arg1 sapiens 566:572 Homo sapiens 561:572 Homo sapiens 561:572 Based on regions of protein sequence conservation between LAM from Bos taurus and Homo sapiens, we cloned cDNA encoding Capra hircus LAM (chLAM). 24660168 1 48 gly glycoproteins 278:290 arg1 glycoproteins 278:290 N-linked glycoproteins 269:290 N-linked glycoproteins 269:290 Lysosomal α-Mannosidase (LAM) belongs to the glycoside hydrolyzing enzymes family 38 and is involved in the biosynthesis and turnover of N-linked glycoproteins process. 24660168 6 49 from sites 987:991 arg1 sites 946:950 the allosteric sites 931:950 the allosteric sites of chLAM 931:959 By homology modeling, molecular docking and mutant analysis, we obtained the probable binding modes of SW at the allosteric sites of chLAM, and the potential mutant sites for the resistance to SW. 24660168 6 49 from sites 987:991 arg1 chLAM 955:959 chLAM 955:959 chLAM 955:959 By homology modeling, molecular docking and mutant analysis, we obtained the probable binding modes of SW at the allosteric sites of chLAM, and the potential mutant sites for the resistance to SW. 24660168 8 50 theme only 1171:1174 arg1 interactions 1176:1187 not only interactions 1167:1187 not only interactions between substrate/SW and chLAM 1167:1218 The obtained results lead to a better understanding of not only interactions between substrate/SW and chLAM, but also of a potential strategy for a novel therapy for locoweed poisoning. 24660168 4 51 theme Pichia 647:652 arg1 pastoris 654:661 Pichia pastoris 647:661 Pichia pastoris 647:661 Expression of cDNA in Pichia pastoris resulted in the secretion of aLAM activity into the culture medium. 24660168 6 52 theme homology 825:832 arg1 modeling 834:841 homology modeling 825:841 homology modeling 825:841 By homology modeling, molecular docking and mutant analysis, we obtained the probable binding modes of SW at the allosteric sites of chLAM, and the potential mutant sites for the resistance to SW. 24660168 7 53 theme mutant 1068:1073 arg1 chLAM 1075:1079 A28 W/G, D58 Y/G mutant chLAM 1051:1079 chLAM 1075:1079 Prediction of SW sensitivity to A28 W/G, D58 Y/G mutant chLAM is lower than wild type chLAM. 24660168 0 54 dep hircus 36:41 arg1 α-mannosidase 53:65 lysosomal α-mannosidase 43:65 lysosomal α-mannosidase 43:65 Molecular characterization of Capra hircus lysosomal α-mannosidase and potential mutant site for the therapy of locoweed poisoning. 24660168 8 55 theme obtained 1116:1123 arg1 results 1125:1131 The obtained results 1112:1131 The obtained results 1112:1131 The obtained results lead to a better understanding of not only interactions between substrate/SW and chLAM, but also of a potential strategy for a novel therapy for locoweed poisoning. 24660168 8 56 theme novel 1260:1264 arg1 therapy 1266:1272 a novel therapy 1258:1272 a novel therapy for locoweed poisoning 1258:1295 The obtained results lead to a better understanding of not only interactions between substrate/SW and chLAM, but also of a potential strategy for a novel therapy for locoweed poisoning. 24660168 2 57 contain contain 318:324 arg2 swainsonine 326:336 swainsonine 326:336 swainsonine (SW) that inhibits LAM 326:359 Locoweeds, which contain swainsonine (SW) that inhibits LAM, are the main poisoning plants in many regions of the world, and thereby resulting in animal poisoning or even death. 24660168 2 57 contain contain 318:324 arg1 plants 385:390 the main poisoning plants 366:390 the main poisoning plants 366:390 Locoweeds, which contain swainsonine (SW) that inhibits LAM, are the main poisoning plants in many regions of the world, and thereby resulting in animal poisoning or even death. 24660168 2 57 contain contain 318:324 arg1 Locoweeds 301:309 Locoweeds 301:309 Locoweeds 301:309 Locoweeds, which contain swainsonine (SW) that inhibits LAM, are the main poisoning plants in many regions of the world, and thereby resulting in animal poisoning or even death. 24660168 2 57 contain contain 318:324 arg2 SW 339:340 SW 339:340 SW 339:340 Locoweeds, which contain swainsonine (SW) that inhibits LAM, are the main poisoning plants in many regions of the world, and thereby resulting in animal poisoning or even death. 24660168 8 58 theme strategy 1245:1252 arg1 understanding 1150:1162 a better understanding 1141:1162 a better understanding of not only interactions between substrate/SW and chLAM, but also of a potential strategy for a novel therapy for locoweed poisoning 1141:1295 The obtained results lead to a better understanding of not only interactions between substrate/SW and chLAM, but also of a potential strategy for a novel therapy for locoweed poisoning. 24660168 7 59 theme wild 1095:1098 arg1 chLAM 1105:1109 wild type chLAM 1095:1109 wild type chLAM 1095:1109 Prediction of SW sensitivity to A28 W/G, D58 Y/G mutant chLAM is lower than wild type chLAM. 24660168 1 60 theme Lysosomal 132:140 arg1 LAM 157:159 LAM 157:159 LAM 157:159 Lysosomal α-Mannosidase (LAM) belongs to the glycoside hydrolyzing enzymes family 38 and is involved in the biosynthesis and turnover of N-linked glycoproteins process. 24660168 1 60 theme Lysosomal 132:140 arg1 α-Mannosidase 142:154 Lysosomal α-Mannosidase 132:154 Lysosomal α-Mannosidase (LAM) 132:160 Lysosomal α-Mannosidase (LAM) belongs to the glycoside hydrolyzing enzymes family 38 and is involved in the biosynthesis and turnover of N-linked glycoproteins process. 24660168 8 61 theme interactions 1176:1187 arg1 understanding 1150:1162 a better understanding 1141:1162 a better understanding of not only interactions between substrate/SW and chLAM, but also of a potential strategy for a novel therapy for locoweed poisoning 1141:1295 The obtained results lead to a better understanding of not only interactions between substrate/SW and chLAM, but also of a potential strategy for a novel therapy for locoweed poisoning. 24660168 4 62 theme culture 715:721 arg1 medium 723:728 the culture medium 711:728 the culture medium 711:728 Expression of cDNA in Pichia pastoris resulted in the secretion of aLAM activity into the culture medium. 24660168 6 63 theme mutant 980:985 arg1 sites 987:991 the potential mutant sites 966:991 the potential mutant sites for the resistance to SW 966:1016 By homology modeling, molecular docking and mutant analysis, we obtained the probable binding modes of SW at the allosteric sites of chLAM, and the potential mutant sites for the resistance to SW. 24660168 6 63 theme mutant 980:985 arg1 SW 925:926 SW 925:926 SW at the allosteric sites of chLAM 925:959 By homology modeling, molecular docking and mutant analysis, we obtained the probable binding modes of SW at the allosteric sites of chLAM, and the potential mutant sites for the resistance to SW. 24660168 6 64 theme binding 908:914 arg1 modes 916:920 the probable binding modes 895:920 the probable binding modes of SW at the allosteric sites of chLAM 895:959 By homology modeling, molecular docking and mutant analysis, we obtained the probable binding modes of SW at the allosteric sites of chLAM, and the potential mutant sites for the resistance to SW. 24660168 0 65 theme mutant 81:86 arg1 site 88:91 potential mutant site 71:91 potential mutant site 71:91 Molecular characterization of Capra hircus lysosomal α-mannosidase and potential mutant site for the therapy of locoweed poisoning. 24660168 2 66 from plants 385:390 arg1 regions 400:406 many regions 395:406 many regions of the world 395:419 Locoweeds, which contain swainsonine (SW) that inhibits LAM, are the main poisoning plants in many regions of the world, and thereby resulting in animal poisoning or even death. 24660168 6 67 theme potential 970:978 arg1 sites 987:991 the potential mutant sites 966:991 the potential mutant sites for the resistance to SW 966:1016 By homology modeling, molecular docking and mutant analysis, we obtained the probable binding modes of SW at the allosteric sites of chLAM, and the potential mutant sites for the resistance to SW. 24660168 6 67 theme potential 970:978 arg1 SW 925:926 SW 925:926 SW at the allosteric sites of chLAM 925:959 By homology modeling, molecular docking and mutant analysis, we obtained the probable binding modes of SW at the allosteric sites of chLAM, and the potential mutant sites for the resistance to SW. 24660168 6 68 theme probable 899:906 arg1 modes 916:920 the probable binding modes 895:920 the probable binding modes of SW at the allosteric sites of chLAM 895:959 By homology modeling, molecular docking and mutant analysis, we obtained the probable binding modes of SW at the allosteric sites of chLAM, and the potential mutant sites for the resistance to SW. 24660168 0 69 theme potential 71:79 arg1 site 88:91 potential mutant site 71:91 potential mutant site 71:91 Molecular characterization of Capra hircus lysosomal α-mannosidase and potential mutant site for the therapy of locoweed poisoning. 24660168 6 70 theme mutant 866:871 arg1 analysis 873:880 mutant analysis 866:880 mutant analysis 866:880 By homology modeling, molecular docking and mutant analysis, we obtained the probable binding modes of SW at the allosteric sites of chLAM, and the potential mutant sites for the resistance to SW. 24660168 1 71 link N-linked 269:276 arg1 glycoproteins 278:290 N-linked glycoproteins 269:290 N-linked glycoproteins 269:290 Lysosomal α-Mannosidase (LAM) belongs to the glycoside hydrolyzing enzymes family 38 and is involved in the biosynthesis and turnover of N-linked glycoproteins process. 24660168 7 72 theme SW 1033:1034 arg1 sensitivity 1036:1046 SW sensitivity 1033:1046 SW sensitivity 1033:1046 Prediction of SW sensitivity to A28 W/G, D58 Y/G mutant chLAM is lower than wild type chLAM. 24660168 3 73 dep hircus 605:610 arg1 chLAM 617:621 chLAM 617:621 chLAM 617:621 Based on regions of protein sequence conservation between LAM from Bos taurus and Homo sapiens, we cloned cDNA encoding Capra hircus LAM (chLAM). 24660168 3 73 dep hircus 605:610 arg1 LAM 612:614 LAM 612:614 Capra hircus LAM (chLAM) 599:622 Based on regions of protein sequence conservation between LAM from Bos taurus and Homo sapiens, we cloned cDNA encoding Capra hircus LAM (chLAM). 25900369 4 0 theme NDPKB 564:568 arg1 mice 575:578 NDPKB(-/-) mice 564:578 NDPKB(-/-) mice 564:578 Therefore, we investigated the impact of NDPKB on retinal vascular damage using NDPKB(-/-) mice during development of DR and its possible mechanisms. 25900369 13 1 theme NDPKB-deficient 1784:1798 arg1 mice 1800:1803 NDPKB-deficient mice 1784:1803 NDPKB-deficient mice 1784:1803 NDPKB-deficient mice are a suitable model for studying mechanisms underlying diabetic retinal vascular damage. 25900369 13 1 theme NDPKB-deficient 1784:1798 arg1 model 1820:1824 a suitable model 1809:1824 a suitable model for studying mechanisms underlying diabetic retinal vascular damage 1809:1892 NDPKB-deficient mice are a suitable model for studying mechanisms underlying diabetic retinal vascular damage. 25900369 2 2 from glucose 330:336 arg1 formation 301:309 the formation 297:309 the formation of UDP-GlcNAc from glucose 297:336 It might therefore supply UTP for the formation of UDP-GlcNAc from glucose. 25900369 11 3 with stimulation 1537:1547 arg1 glucose 1559:1565 high glucose 1554:1565 high glucose 1554:1565 In cultured endothelial cells, stimulation with high glucose and NDPKB depletion comparably increased Ang2 expression and protein GlcNAcylation. 25900369 11 3 with stimulation 1537:1547 arg1 depletion 1577:1585 NDPKB depletion 1571:1585 NDPKB depletion 1571:1585 In cultured endothelial cells, stimulation with high glucose and NDPKB depletion comparably increased Ang2 expression and protein GlcNAcylation. 25900369 11 4 theme protein 1628:1634 arg1 GlcNAcylation 1636:1648 protein GlcNAcylation 1628:1648 protein GlcNAcylation 1628:1648 In cultured endothelial cells, stimulation with high glucose and NDPKB depletion comparably increased Ang2 expression and protein GlcNAcylation. 25900369 7 5 theme diabetic 1069:1076 arg1 retinas 1081:1087 diabetic WT retinas 1069:1087 diabetic WT retinas 1069:1087 RESULTS Similar to diabetic WT retinas, non-diabetic NDPKB(-/-) retinas showed a significant decrease in pericyte coverage in comparison with non-diabetic WT retinas. 25900369 12 6 dep CONCLUSIONS 1651:1661 arg1 identify 1672:1679 identify 1672:1679 identify NDPKB as a protective factor in the retina, which controls Ang2 expression and the hexosamine pathway 1672:1781 CONCLUSIONS Our data identify NDPKB as a protective factor in the retina, which controls Ang2 expression and the hexosamine pathway. 25900369 6 7 theme modification 848:859 arg1 Expression 780:789 Expression 780:789 Expression of angiopoietin-2 (Ang2) and protein N-acetylglucosamine modification (GlcNAcylation) 780:875 Expression of angiopoietin-2 (Ang2) and protein N-acetylglucosamine modification (GlcNAcylation) were assessed by western blot and/or immunofluorescence in the diabetic retinas as well as in endothelial cells depleted of NDPKB by siRNA and stimulated with high glucose. 25900369 4 8 theme mechanisms 622:631 arg1 development 587:597 development 587:597 development of DR and its possible mechanisms 587:631 Therefore, we investigated the impact of NDPKB on retinal vascular damage using NDPKB(-/-) mice during development of DR and its possible mechanisms. 25900369 7 9 theme Similar 1058:1064 arg1 RESULTS 1050:1056 RESULTS 1050:1056 RESULTS Similar to diabetic WT retinas 1050:1087 RESULTS Similar to diabetic WT retinas, non-diabetic NDPKB(-/-) retinas showed a significant decrease in pericyte coverage in comparison with non-diabetic WT retinas. 25900369 7 9 theme Similar 1058:1064 arg1 retinas 1114:1120 non-diabetic NDPKB(-/-) retinas 1090:1120 non-diabetic NDPKB(-/-) retinas 1090:1120 RESULTS Similar to diabetic WT retinas, non-diabetic NDPKB(-/-) retinas showed a significant decrease in pericyte coverage in comparison with non-diabetic WT retinas. 25900369 11 10 theme cultured 1509:1516 arg1 cells 1530:1534 cultured endothelial cells 1509:1534 cultured endothelial cells 1509:1534 In cultured endothelial cells, stimulation with high glucose and NDPKB depletion comparably increased Ang2 expression and protein GlcNAcylation. 25900369 0 11 theme Nucleoside 0:9 arg1 kinase 23:28 Nucleoside diphosphate kinase 0:28 Nucleoside diphosphate kinase B deficiency 0:41 Nucleoside diphosphate kinase B deficiency causes a diabetes-like vascular pathology via up-regulation of endothelial angiopoietin-2 in the retina. 25900369 6 12 theme protein 820:826 arg1 modification 848:859 protein N-acetylglucosamine modification (GlcNAcylation) 820:875 protein N-acetylglucosamine modification (GlcNAcylation) 820:875 Expression of angiopoietin-2 (Ang2) and protein N-acetylglucosamine modification (GlcNAcylation) were assessed by western blot and/or immunofluorescence in the diabetic retinas as well as in endothelial cells depleted of NDPKB by siRNA and stimulated with high glucose. 25900369 6 12 theme protein 820:826 arg1 GlcNAcylation 862:874 GlcNAcylation 862:874 GlcNAcylation 862:874 Expression of angiopoietin-2 (Ang2) and protein N-acetylglucosamine modification (GlcNAcylation) were assessed by western blot and/or immunofluorescence in the diabetic retinas as well as in endothelial cells depleted of NDPKB by siRNA and stimulated with high glucose. 25900369 12 13 theme protective 1692:1701 arg1 NDPKB 1681:1685 NDPKB 1681:1685 NDPKB 1681:1685 CONCLUSIONS Our data identify NDPKB as a protective factor in the retina, which controls Ang2 expression and the hexosamine pathway. 25900369 12 13 theme protective 1692:1701 arg1 factor 1703:1708 a protective factor 1690:1708 a protective factor 1690:1708 CONCLUSIONS Our data identify NDPKB as a protective factor in the retina, which controls Ang2 expression and the hexosamine pathway. 25900369 2 14 theme UDP-GlcNAc 314:323 arg1 formation 301:309 the formation 297:309 the formation of UDP-GlcNAc from glucose 297:336 It might therefore supply UTP for the formation of UDP-GlcNAc from glucose. 25900369 4 15 theme DR 602:603 arg1 development 587:597 development 587:597 development of DR and its possible mechanisms 587:631 Therefore, we investigated the impact of NDPKB on retinal vascular damage using NDPKB(-/-) mice during development of DR and its possible mechanisms. 25900369 7 16 from coverage 1164:1171 arg1 comparison 1176:1185 comparison 1176:1185 comparison with non-diabetic WT retinas 1176:1214 RESULTS Similar to diabetic WT retinas, non-diabetic NDPKB(-/-) retinas showed a significant decrease in pericyte coverage in comparison with non-diabetic WT retinas. 25900369 8 17 theme diabetic 1267:1274 arg1 retinas 1287:1293 diabetic NDPKB(-/-) retinas 1267:1293 diabetic NDPKB(-/-) retinas 1267:1293 Hyperglycemia further aggravates pericyte loss in diabetic NDPKB(-/-) retinas. 25900369 5 18 theme acellular 660:668 arg1 formation 685:693 acellular capillary (AC) formation 660:693 acellular capillary (AC) formation 660:693 METHODS Pericyte loss and acellular capillary (AC) formation were assessed in streptozotocin-induced diabetic NDPKB(-/-) and wild-type (WT) mice. 25900369 5 18 theme acellular 660:668 arg1 METHODS 634:640 METHODS 634:640 METHODS Pericyte loss and acellular capillary (AC) formation 634:693 METHODS Pericyte loss and acellular capillary (AC) formation were assessed in streptozotocin-induced diabetic NDPKB(-/-) and wild-type (WT) mice. 25900369 4 19 dep mice 575:578 arg1 -/- 570:572 -/- 570:572 -/- 570:572 Therefore, we investigated the impact of NDPKB on retinal vascular damage using NDPKB(-/-) mice during development of DR and its possible mechanisms. 25900369 0 20 theme vascular 66:73 arg1 pathology 75:83 a diabetes-like vascular pathology 50:83 a diabetes-like vascular pathology 50:83 Nucleoside diphosphate kinase B deficiency causes a diabetes-like vascular pathology via up-regulation of endothelial angiopoietin-2 in the retina. 25900369 1 21 theme diphosphate 164:174 arg1 NDPKB 186:190 NDPKB 186:190 NDPKB 186:190 AIMS Nucleoside diphosphate kinase B (NDPKB) is capable of maintaining the cellular nucleotide triphosphate pools. 25900369 1 21 theme diphosphate 164:174 arg1 B 183:183 Nucleoside diphosphate kinase B 153:183 Nucleoside diphosphate kinase B (NDPKB) 153:191 AIMS Nucleoside diphosphate kinase B (NDPKB) is capable of maintaining the cellular nucleotide triphosphate pools. 25900369 10 22 theme NDPKB 1384:1388 arg1 deficiency 1390:1399 NDPKB deficiency 1384:1399 NDPKB deficiency 1384:1399 Similar to hyperglycemia, NDPKB deficiency induced Ang2 expression and protein GlcNAcylation that were not further altered in the diabetic retinas. 25900369 13 23 theme diabetic 1861:1868 arg1 damage 1887:1892 diabetic retinal vascular damage 1861:1892 diabetic retinal vascular damage 1861:1892 NDPKB-deficient mice are a suitable model for studying mechanisms underlying diabetic retinal vascular damage. 25900369 3 24 theme vascular 363:370 arg1 dysfunction 372:382 vascular dysfunction 363:382 vascular dysfunction 363:382 As NDPKB contributes to vascular dysfunction, we speculate that NDPKB might play a role in microangiopathies, such as diabetic retinopathy (DR). 25900369 13 25 theme vascular 1878:1885 arg1 damage 1887:1892 diabetic retinal vascular damage 1861:1892 diabetic retinal vascular damage 1861:1892 NDPKB-deficient mice are a suitable model for studying mechanisms underlying diabetic retinal vascular damage. 25900369 8 26 from loss 1259:1262 arg1 retinas 1287:1293 diabetic NDPKB(-/-) retinas 1267:1293 diabetic NDPKB(-/-) retinas 1267:1293 Hyperglycemia further aggravates pericyte loss in diabetic NDPKB(-/-) retinas. 25900369 0 27 theme angiopoietin-2 118:131 arg1 up-regulation 89:101 up-regulation 89:101 up-regulation of endothelial angiopoietin-2 in the retina 89:145 Nucleoside diphosphate kinase B deficiency causes a diabetes-like vascular pathology via up-regulation of endothelial angiopoietin-2 in the retina. 25900369 6 28 dep cells 983:987 arg1 stimulated 1020:1029 stimulated 1020:1029 stimulated with high glucose 1020:1047 Expression of angiopoietin-2 (Ang2) and protein N-acetylglucosamine modification (GlcNAcylation) were assessed by western blot and/or immunofluorescence in the diabetic retinas as well as in endothelial cells depleted of NDPKB by siRNA and stimulated with high glucose. 25900369 6 28 dep cells 983:987 arg1 depleted 989:996 depleted 989:996 depleted of NDPKB by siRNA 989:1014 Expression of angiopoietin-2 (Ang2) and protein N-acetylglucosamine modification (GlcNAcylation) were assessed by western blot and/or immunofluorescence in the diabetic retinas as well as in endothelial cells depleted of NDPKB by siRNA and stimulated with high glucose. 25900369 7 29 dep NDPKB 1103:1107 arg1 -/- 1109:1111 -/- 1109:1111 -/- 1109:1111 RESULTS Similar to diabetic WT retinas, non-diabetic NDPKB(-/-) retinas showed a significant decrease in pericyte coverage in comparison with non-diabetic WT retinas. 25900369 5 30 theme WT 770:771 arg1 mice 774:777 streptozotocin-induced diabetic NDPKB(-/-) and wild-type (WT) mice 712:777 mice 774:777 METHODS Pericyte loss and acellular capillary (AC) formation were assessed in streptozotocin-induced diabetic NDPKB(-/-) and wild-type (WT) mice. 25900369 3 31 theme diabetic 457:464 arg1 DR 479:480 DR 479:480 DR 479:480 As NDPKB contributes to vascular dysfunction, we speculate that NDPKB might play a role in microangiopathies, such as diabetic retinopathy (DR). 25900369 3 31 theme diabetic 457:464 arg1 retinopathy 466:476 diabetic retinopathy 457:476 diabetic retinopathy (DR) 457:481 As NDPKB contributes to vascular dysfunction, we speculate that NDPKB might play a role in microangiopathies, such as diabetic retinopathy (DR). 25900369 0 32 theme kinase 23:28 arg1 deficiency 32:41 Nucleoside diphosphate kinase B deficiency 0:41 Nucleoside diphosphate kinase B deficiency 0:41 Nucleoside diphosphate kinase B deficiency causes a diabetes-like vascular pathology via up-regulation of endothelial angiopoietin-2 in the retina. 25900369 9 33 theme AC 1296:1297 arg1 formation 1299:1307 AC formation 1296:1307 AC formation 1296:1307 AC formation was detected in the diabetic NDPKB(-/-) retinas. 25900369 4 34 theme vascular 542:549 arg1 damage 551:556 retinal vascular damage 534:556 retinal vascular damage 534:556 Therefore, we investigated the impact of NDPKB on retinal vascular damage using NDPKB(-/-) mice during development of DR and its possible mechanisms. 25900369 10 35 theme protein 1429:1435 arg1 GlcNAcylation 1437:1449 protein GlcNAcylation 1429:1449 protein GlcNAcylation 1429:1449 Similar to hyperglycemia, NDPKB deficiency induced Ang2 expression and protein GlcNAcylation that were not further altered in the diabetic retinas. 25900369 13 36 theme suitable 1811:1818 arg1 mice 1800:1803 NDPKB-deficient mice 1784:1803 NDPKB-deficient mice 1784:1803 NDPKB-deficient mice are a suitable model for studying mechanisms underlying diabetic retinal vascular damage. 25900369 13 36 theme suitable 1811:1818 arg1 model 1820:1824 a suitable model 1809:1824 a suitable model for studying mechanisms underlying diabetic retinal vascular damage 1809:1892 NDPKB-deficient mice are a suitable model for studying mechanisms underlying diabetic retinal vascular damage. 25900369 5 37 theme wild-type 759:767 arg1 mice 774:777 streptozotocin-induced diabetic NDPKB(-/-) and wild-type (WT) mice 712:777 mice 774:777 METHODS Pericyte loss and acellular capillary (AC) formation were assessed in streptozotocin-induced diabetic NDPKB(-/-) and wild-type (WT) mice. 25900369 6 38 theme angiopoietin-2 794:807 arg1 Expression 780:789 Expression 780:789 Expression of angiopoietin-2 (Ang2) and protein N-acetylglucosamine modification (GlcNAcylation) 780:875 Expression of angiopoietin-2 (Ang2) and protein N-acetylglucosamine modification (GlcNAcylation) were assessed by western blot and/or immunofluorescence in the diabetic retinas as well as in endothelial cells depleted of NDPKB by siRNA and stimulated with high glucose. 25900369 9 39 theme diabetic 1329:1336 arg1 retinas 1349:1355 the diabetic NDPKB(-/-) retinas 1325:1355 the diabetic NDPKB(-/-) retinas 1325:1355 AC formation was detected in the diabetic NDPKB(-/-) retinas. 25900369 8 40 theme NDPKB 1276:1280 arg1 retinas 1287:1293 diabetic NDPKB(-/-) retinas 1267:1293 diabetic NDPKB(-/-) retinas 1267:1293 Hyperglycemia further aggravates pericyte loss in diabetic NDPKB(-/-) retinas. 25900369 11 41 theme NDPKB 1571:1575 arg1 depletion 1577:1585 NDPKB depletion 1571:1585 NDPKB depletion 1571:1585 In cultured endothelial cells, stimulation with high glucose and NDPKB depletion comparably increased Ang2 expression and protein GlcNAcylation. 25900369 1 42 theme triphosphate 243:254 arg1 pools 256:260 the cellular nucleotide triphosphate pools 219:260 the cellular nucleotide triphosphate pools 219:260 AIMS Nucleoside diphosphate kinase B (NDPKB) is capable of maintaining the cellular nucleotide triphosphate pools. 25900369 0 43 theme diabetes-like 52:64 arg1 pathology 75:83 a diabetes-like vascular pathology 50:83 a diabetes-like vascular pathology 50:83 Nucleoside diphosphate kinase B deficiency causes a diabetes-like vascular pathology via up-regulation of endothelial angiopoietin-2 in the retina. 25900369 11 44 theme Ang2 1608:1611 arg1 expression 1613:1622 Ang2 expression 1608:1622 Ang2 expression 1608:1622 In cultured endothelial cells, stimulation with high glucose and NDPKB depletion comparably increased Ang2 expression and protein GlcNAcylation. 25900369 7 45 theme WT 1078:1079 arg1 retinas 1081:1087 diabetic WT retinas 1069:1087 diabetic WT retinas 1069:1087 RESULTS Similar to diabetic WT retinas, non-diabetic NDPKB(-/-) retinas showed a significant decrease in pericyte coverage in comparison with non-diabetic WT retinas. 25900369 7 46 theme non-diabetic 1192:1203 arg1 retinas 1208:1214 non-diabetic WT retinas 1192:1214 non-diabetic WT retinas 1192:1214 RESULTS Similar to diabetic WT retinas, non-diabetic NDPKB(-/-) retinas showed a significant decrease in pericyte coverage in comparison with non-diabetic WT retinas. 25900369 7 47 theme non-diabetic 1090:1101 arg1 RESULTS 1050:1056 RESULTS 1050:1056 RESULTS Similar to diabetic WT retinas 1050:1087 RESULTS Similar to diabetic WT retinas, non-diabetic NDPKB(-/-) retinas showed a significant decrease in pericyte coverage in comparison with non-diabetic WT retinas. 25900369 7 47 theme non-diabetic 1090:1101 arg1 retinas 1114:1120 non-diabetic NDPKB(-/-) retinas 1090:1120 non-diabetic NDPKB(-/-) retinas 1090:1120 RESULTS Similar to diabetic WT retinas, non-diabetic NDPKB(-/-) retinas showed a significant decrease in pericyte coverage in comparison with non-diabetic WT retinas. 25900369 6 48 theme N-acetylglucosamine 828:846 arg1 modification 848:859 protein N-acetylglucosamine modification (GlcNAcylation) 820:875 protein N-acetylglucosamine modification (GlcNAcylation) 820:875 Expression of angiopoietin-2 (Ang2) and protein N-acetylglucosamine modification (GlcNAcylation) were assessed by western blot and/or immunofluorescence in the diabetic retinas as well as in endothelial cells depleted of NDPKB by siRNA and stimulated with high glucose. 25900369 6 48 theme N-acetylglucosamine 828:846 arg1 GlcNAcylation 862:874 GlcNAcylation 862:874 GlcNAcylation 862:874 Expression of angiopoietin-2 (Ang2) and protein N-acetylglucosamine modification (GlcNAcylation) were assessed by western blot and/or immunofluorescence in the diabetic retinas as well as in endothelial cells depleted of NDPKB by siRNA and stimulated with high glucose. 25900369 4 49 theme possible 613:620 arg1 mechanisms 622:631 its possible mechanisms 609:631 its possible mechanisms 609:631 Therefore, we investigated the impact of NDPKB on retinal vascular damage using NDPKB(-/-) mice during development of DR and its possible mechanisms. 25900369 11 50 theme endothelial 1518:1528 arg1 cells 1530:1534 cultured endothelial cells 1509:1534 cultured endothelial cells 1509:1534 In cultured endothelial cells, stimulation with high glucose and NDPKB depletion comparably increased Ang2 expression and protein GlcNAcylation. 25900369 6 51 theme diabetic 940:947 arg1 retinas 949:955 the diabetic retinas 936:955 the diabetic retinas as well as in endothelial cells depleted of NDPKB by siRNA and stimulated with high glucose 936:1047 Expression of angiopoietin-2 (Ang2) and protein N-acetylglucosamine modification (GlcNAcylation) were assessed by western blot and/or immunofluorescence in the diabetic retinas as well as in endothelial cells depleted of NDPKB by siRNA and stimulated with high glucose. 25900369 10 52 gly GlcNAcylation 1437:1449 arg1 retinas 1497:1503 the diabetic retinas 1484:1503 the diabetic retinas 1484:1503 Similar to hyperglycemia, NDPKB deficiency induced Ang2 expression and protein GlcNAcylation that were not further altered in the diabetic retinas. 25900369 5 53 theme capillary 670:678 arg1 formation 685:693 acellular capillary (AC) formation 660:693 acellular capillary (AC) formation 660:693 METHODS Pericyte loss and acellular capillary (AC) formation were assessed in streptozotocin-induced diabetic NDPKB(-/-) and wild-type (WT) mice. 25900369 5 53 theme capillary 670:678 arg1 METHODS 634:640 METHODS 634:640 METHODS Pericyte loss and acellular capillary (AC) formation 634:693 METHODS Pericyte loss and acellular capillary (AC) formation were assessed in streptozotocin-induced diabetic NDPKB(-/-) and wild-type (WT) mice. 25900369 0 54 from up-regulation 89:101 arg1 retina 140:145 the retina 136:145 the retina 136:145 Nucleoside diphosphate kinase B deficiency causes a diabetes-like vascular pathology via up-regulation of endothelial angiopoietin-2 in the retina. 25900369 5 55 theme AC 681:682 arg1 formation 685:693 acellular capillary (AC) formation 660:693 acellular capillary (AC) formation 660:693 METHODS Pericyte loss and acellular capillary (AC) formation were assessed in streptozotocin-induced diabetic NDPKB(-/-) and wild-type (WT) mice. 25900369 5 55 theme AC 681:682 arg1 METHODS 634:640 METHODS 634:640 METHODS Pericyte loss and acellular capillary (AC) formation 634:693 METHODS Pericyte loss and acellular capillary (AC) formation were assessed in streptozotocin-induced diabetic NDPKB(-/-) and wild-type (WT) mice. 25900369 7 56 from decrease 1143:1150 arg1 coverage 1164:1171 pericyte coverage 1155:1171 pericyte coverage in comparison with non-diabetic WT retinas 1155:1214 RESULTS Similar to diabetic WT retinas, non-diabetic NDPKB(-/-) retinas showed a significant decrease in pericyte coverage in comparison with non-diabetic WT retinas. 25900369 5 57 theme Pericyte 642:649 arg1 loss 651:654 Pericyte loss 642:654 Pericyte loss 642:654 METHODS Pericyte loss and acellular capillary (AC) formation were assessed in streptozotocin-induced diabetic NDPKB(-/-) and wild-type (WT) mice. 25900369 5 57 theme Pericyte 642:649 arg1 METHODS 634:640 METHODS 634:640 METHODS Pericyte loss and acellular capillary (AC) formation 634:693 METHODS Pericyte loss and acellular capillary (AC) formation were assessed in streptozotocin-induced diabetic NDPKB(-/-) and wild-type (WT) mice. 25900369 6 58 theme western 894:900 arg1 blot 902:905 western blot 894:905 western blot 894:905 Expression of angiopoietin-2 (Ang2) and protein N-acetylglucosamine modification (GlcNAcylation) were assessed by western blot and/or immunofluorescence in the diabetic retinas as well as in endothelial cells depleted of NDPKB by siRNA and stimulated with high glucose. 25900369 8 59 theme pericyte 1250:1257 arg1 loss 1259:1262 pericyte loss 1250:1262 pericyte loss in diabetic NDPKB(-/-) retinas 1250:1293 Hyperglycemia further aggravates pericyte loss in diabetic NDPKB(-/-) retinas. 25900369 9 60 located detected 1313:1320 arg1 retinas 1349:1355 the diabetic NDPKB(-/-) retinas 1325:1355 the diabetic NDPKB(-/-) retinas 1325:1355 AC formation was detected in the diabetic NDPKB(-/-) retinas. 25900369 9 60 located detected 1313:1320 arg2 formation 1299:1307 AC formation 1296:1307 AC formation 1296:1307 AC formation was detected in the diabetic NDPKB(-/-) retinas. 25900369 1 61 theme Nucleoside 153:162 arg1 NDPKB 186:190 NDPKB 186:190 NDPKB 186:190 AIMS Nucleoside diphosphate kinase B (NDPKB) is capable of maintaining the cellular nucleotide triphosphate pools. 25900369 1 61 theme Nucleoside 153:162 arg1 B 183:183 Nucleoside diphosphate kinase B 153:183 Nucleoside diphosphate kinase B (NDPKB) 153:191 AIMS Nucleoside diphosphate kinase B (NDPKB) is capable of maintaining the cellular nucleotide triphosphate pools. 25900369 6 62 theme endothelial 971:981 arg1 cells 983:987 endothelial cells 971:987 endothelial cells depleted of NDPKB by siRNA and stimulated with high glucose 971:1047 Expression of angiopoietin-2 (Ang2) and protein N-acetylglucosamine modification (GlcNAcylation) were assessed by western blot and/or immunofluorescence in the diabetic retinas as well as in endothelial cells depleted of NDPKB by siRNA and stimulated with high glucose. 25900369 7 63 with comparison 1176:1185 arg1 retinas 1208:1214 non-diabetic WT retinas 1192:1214 non-diabetic WT retinas 1192:1214 RESULTS Similar to diabetic WT retinas, non-diabetic NDPKB(-/-) retinas showed a significant decrease in pericyte coverage in comparison with non-diabetic WT retinas. 25900369 1 64 theme cellular 223:230 arg1 pools 256:260 the cellular nucleotide triphosphate pools 219:260 the cellular nucleotide triphosphate pools 219:260 AIMS Nucleoside diphosphate kinase B (NDPKB) is capable of maintaining the cellular nucleotide triphosphate pools. 25900369 7 65 theme pericyte 1155:1162 arg1 coverage 1164:1171 pericyte coverage 1155:1171 pericyte coverage in comparison with non-diabetic WT retinas 1155:1214 RESULTS Similar to diabetic WT retinas, non-diabetic NDPKB(-/-) retinas showed a significant decrease in pericyte coverage in comparison with non-diabetic WT retinas. 25900369 1 66 theme kinase 176:181 arg1 NDPKB 186:190 NDPKB 186:190 NDPKB 186:190 AIMS Nucleoside diphosphate kinase B (NDPKB) is capable of maintaining the cellular nucleotide triphosphate pools. 25900369 1 66 theme kinase 176:181 arg1 B 183:183 Nucleoside diphosphate kinase B 153:183 Nucleoside diphosphate kinase B (NDPKB) 153:191 AIMS Nucleoside diphosphate kinase B (NDPKB) is capable of maintaining the cellular nucleotide triphosphate pools. 25900369 8 67 theme -/- 1282:1284 arg1 retinas 1287:1293 diabetic NDPKB(-/-) retinas 1267:1293 diabetic NDPKB(-/-) retinas 1267:1293 Hyperglycemia further aggravates pericyte loss in diabetic NDPKB(-/-) retinas. 25900369 13 68 theme retinal 1870:1876 arg1 damage 1887:1892 diabetic retinal vascular damage 1861:1892 diabetic retinal vascular damage 1861:1892 NDPKB-deficient mice are a suitable model for studying mechanisms underlying diabetic retinal vascular damage. 25900369 0 69 theme endothelial 106:116 arg1 angiopoietin-2 118:131 endothelial angiopoietin-2 106:131 endothelial angiopoietin-2 106:131 Nucleoside diphosphate kinase B deficiency causes a diabetes-like vascular pathology via up-regulation of endothelial angiopoietin-2 in the retina. 25900369 1 70 dep AIMS 148:151 arg1 capable 196:202 capable 196:202 capable 196:202 AIMS Nucleoside diphosphate kinase B (NDPKB) is capable of maintaining the cellular nucleotide triphosphate pools. 25900369 6 71 theme high 1036:1039 arg1 glucose 1041:1047 high glucose 1036:1047 high glucose 1036:1047 Expression of angiopoietin-2 (Ang2) and protein N-acetylglucosamine modification (GlcNAcylation) were assessed by western blot and/or immunofluorescence in the diabetic retinas as well as in endothelial cells depleted of NDPKB by siRNA and stimulated with high glucose. 25900369 10 72 theme Ang2 1409:1412 arg1 expression 1414:1423 Ang2 expression 1409:1423 Ang2 expression 1409:1423 Similar to hyperglycemia, NDPKB deficiency induced Ang2 expression and protein GlcNAcylation that were not further altered in the diabetic retinas. 25900369 1 73 theme nucleotide 232:241 arg1 pools 256:260 the cellular nucleotide triphosphate pools 219:260 the cellular nucleotide triphosphate pools 219:260 AIMS Nucleoside diphosphate kinase B (NDPKB) is capable of maintaining the cellular nucleotide triphosphate pools. 25900369 0 74 theme diphosphate 11:21 arg1 kinase 23:28 Nucleoside diphosphate kinase 0:28 Nucleoside diphosphate kinase B deficiency 0:41 Nucleoside diphosphate kinase B deficiency causes a diabetes-like vascular pathology via up-regulation of endothelial angiopoietin-2 in the retina. 25900369 5 75 dep METHODS 634:640 arg1 formation 685:693 acellular capillary (AC) formation 660:693 acellular capillary (AC) formation 660:693 METHODS Pericyte loss and acellular capillary (AC) formation were assessed in streptozotocin-induced diabetic NDPKB(-/-) and wild-type (WT) mice. 25900369 5 75 dep METHODS 634:640 arg1 loss 651:654 Pericyte loss 642:654 Pericyte loss 642:654 METHODS Pericyte loss and acellular capillary (AC) formation were assessed in streptozotocin-induced diabetic NDPKB(-/-) and wild-type (WT) mice. 25900369 5 75 dep METHODS 634:640 arg1 METHODS 634:640 METHODS 634:640 METHODS Pericyte loss and acellular capillary (AC) formation 634:693 METHODS Pericyte loss and acellular capillary (AC) formation were assessed in streptozotocin-induced diabetic NDPKB(-/-) and wild-type (WT) mice. 25900369 4 76 theme retinal 534:540 arg1 damage 551:556 retinal vascular damage 534:556 retinal vascular damage 534:556 Therefore, we investigated the impact of NDPKB on retinal vascular damage using NDPKB(-/-) mice during development of DR and its possible mechanisms. 25900369 0 77 theme B 30:30 arg1 deficiency 32:41 Nucleoside diphosphate kinase B deficiency 0:41 Nucleoside diphosphate kinase B deficiency 0:41 Nucleoside diphosphate kinase B deficiency causes a diabetes-like vascular pathology via up-regulation of endothelial angiopoietin-2 in the retina. 25900369 7 78 theme NDPKB 1103:1107 arg1 RESULTS 1050:1056 RESULTS 1050:1056 RESULTS Similar to diabetic WT retinas 1050:1087 RESULTS Similar to diabetic WT retinas, non-diabetic NDPKB(-/-) retinas showed a significant decrease in pericyte coverage in comparison with non-diabetic WT retinas. 25900369 7 78 theme NDPKB 1103:1107 arg1 retinas 1114:1120 non-diabetic NDPKB(-/-) retinas 1090:1120 non-diabetic NDPKB(-/-) retinas 1090:1120 RESULTS Similar to diabetic WT retinas, non-diabetic NDPKB(-/-) retinas showed a significant decrease in pericyte coverage in comparison with non-diabetic WT retinas. 25900369 12 79 from factor 1703:1708 arg1 retina 1717:1722 the retina 1713:1722 the retina 1713:1722 CONCLUSIONS Our data identify NDPKB as a protective factor in the retina, which controls Ang2 expression and the hexosamine pathway. 25900369 7 80 theme significant 1131:1141 arg1 decrease 1143:1150 a significant decrease 1129:1150 a significant decrease in pericyte coverage in comparison with non-diabetic WT retinas 1129:1214 RESULTS Similar to diabetic WT retinas, non-diabetic NDPKB(-/-) retinas showed a significant decrease in pericyte coverage in comparison with non-diabetic WT retinas. 25900369 4 81 from impact 515:520 arg1 damage 551:556 retinal vascular damage 534:556 retinal vascular damage 534:556 Therefore, we investigated the impact of NDPKB on retinal vascular damage using NDPKB(-/-) mice during development of DR and its possible mechanisms. 25900369 12 82 theme hexosamine 1764:1773 arg1 pathway 1775:1781 the hexosamine pathway 1760:1781 the hexosamine pathway 1760:1781 CONCLUSIONS Our data identify NDPKB as a protective factor in the retina, which controls Ang2 expression and the hexosamine pathway. 25900369 4 83 theme NDPKB 525:529 arg1 impact 515:520 the impact 511:520 the impact of NDPKB on retinal vascular damage 511:556 Therefore, we investigated the impact of NDPKB on retinal vascular damage using NDPKB(-/-) mice during development of DR and its possible mechanisms. 25900369 9 84 theme NDPKB 1338:1342 arg1 retinas 1349:1355 the diabetic NDPKB(-/-) retinas 1325:1355 the diabetic NDPKB(-/-) retinas 1325:1355 AC formation was detected in the diabetic NDPKB(-/-) retinas. 25900369 12 85 theme Ang2 1740:1743 arg1 expression 1745:1754 Ang2 expression 1740:1754 Ang2 expression 1740:1754 CONCLUSIONS Our data identify NDPKB as a protective factor in the retina, which controls Ang2 expression and the hexosamine pathway. 25900369 7 86 theme WT 1205:1206 arg1 retinas 1208:1214 non-diabetic WT retinas 1192:1214 non-diabetic WT retinas 1192:1214 RESULTS Similar to diabetic WT retinas, non-diabetic NDPKB(-/-) retinas showed a significant decrease in pericyte coverage in comparison with non-diabetic WT retinas. 25900369 10 87 theme diabetic 1488:1495 arg1 retinas 1497:1503 the diabetic retinas 1484:1503 the diabetic retinas 1484:1503 Similar to hyperglycemia, NDPKB deficiency induced Ang2 expression and protein GlcNAcylation that were not further altered in the diabetic retinas. 25900369 11 88 theme high 1554:1557 arg1 glucose 1559:1565 high glucose 1554:1565 high glucose 1554:1565 In cultured endothelial cells, stimulation with high glucose and NDPKB depletion comparably increased Ang2 expression and protein GlcNAcylation. 25900369 9 89 theme -/- 1344:1346 arg1 retinas 1349:1355 the diabetic NDPKB(-/-) retinas 1325:1355 the diabetic NDPKB(-/-) retinas 1325:1355 AC formation was detected in the diabetic NDPKB(-/-) retinas. 27477117 3 0 theme collision-induced 688:704 arg1 CID 721:723 CID 721:723 CID 721:723 Some isomers, such as Man3 GlcNAc3 from chicken ovalbumin and Man3 GlcNAc3 Fuc1 from thyroglobulin could be partially resolved and identified by their negative ion fragmentation spectra obtained by collision-induced decomposition (CID). 27477117 3 0 theme collision-induced 688:704 arg1 decomposition 706:718 collision-induced decomposition 688:718 collision-induced decomposition (CID) 688:724 Some isomers, such as Man3 GlcNAc3 from chicken ovalbumin and Man3 GlcNAc3 Fuc1 from thyroglobulin could be partially resolved and identified by their negative ion fragmentation spectra obtained by collision-induced decomposition (CID). 27477117 6 1 theme high-mannose 1241:1252 arg1 glycans 1254:1260 high-mannose glycans 1241:1260 high-mannose glycans 1241:1260 Coincidence in the drift times of all fragment ions with an asymmetric ATD profile in this work, and in the related earlier paper on high-mannose glycans, usually suggested that separations were because of conformers or anomers, whereas symmetrical ATDs of fragments showing differences in drift times indicated isomer separation. 27477117 1 2 theme immunodeficiency 239:254 arg1 virus 256:260 human immunodeficiency virus 233:260 human immunodeficiency virus 233:260 Nitrogen collisional cross sections (CCSs) of hybrid and complex glycans released from the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin were measured with a travelling-wave ion mobility mass spectrometer using dextran as the calibrant. 27477117 9 3 theme core 1886:1889 arg1 fucose 1891:1896 a core fucose 1884:1896 a core fucose 1884:1896 In addition, biantennary glycans containing a core fucose and/or a bisecting GlcNAc residue fell on different mobility-m/z trend lines to those glycans not so substituted with both of these substituents contributing to larger CCSs. 27477117 4 4 theme time 851:854 arg1 distributions 856:868 separated arrival time distributions 833:868 only asymmetric rather than separated arrival time distributions (ATDs) 805:875 Several other larger glycans, however, although existing as isomers, produced only asymmetric rather than separated arrival time distributions (ATDs). 27477117 4 4 theme time 851:854 arg1 ATDs 871:874 ATDs 871:874 ATDs 871:874 Several other larger glycans, however, although existing as isomers, produced only asymmetric rather than separated arrival time distributions (ATDs). 27477117 6 5 theme ions 1155:1158 arg1 times 1133:1137 the drift times 1123:1137 the drift times of all fragment ions with an asymmetric ATD profile in this work 1123:1202 Coincidence in the drift times of all fragment ions with an asymmetric ATD profile in this work, and in the related earlier paper on high-mannose glycans, usually suggested that separations were because of conformers or anomers, whereas symmetrical ATDs of fragments showing differences in drift times indicated isomer separation. 27477117 6 6 theme related 1216:1222 arg1 paper 1232:1236 the related earlier paper 1212:1236 the related earlier paper on high-mannose glycans 1212:1260 Coincidence in the drift times of all fragment ions with an asymmetric ATD profile in this work, and in the related earlier paper on high-mannose glycans, usually suggested that separations were because of conformers or anomers, whereas symmetrical ATDs of fragments showing differences in drift times indicated isomer separation. 27477117 4 7 dep produced 796:803 arg1 existing 775:782 existing 775:782 existing as isomers 775:793 Several other larger glycans, however, although existing as isomers, produced only asymmetric rather than separated arrival time distributions (ATDs). 27477117 9 8 theme bisecting 1907:1915 arg1 residue 1924:1930 a bisecting GlcNAc residue 1905:1930 a bisecting GlcNAc residue 1905:1930 In addition, biantennary glycans containing a core fucose and/or a bisecting GlcNAc residue fell on different mobility-m/z trend lines to those glycans not so substituted with both of these substituents contributing to larger CCSs. 27477117 1 9 gly glycoproteins 202:214 arg1 thyroglobulin 300:312 thyroglobulin 300:312 thyroglobulin 300:312 Nitrogen collisional cross sections (CCSs) of hybrid and complex glycans released from the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin were measured with a travelling-wave ion mobility mass spectrometer using dextran as the calibrant. 27477117 1 9 gly glycoproteins 202:214 arg1 gp120 221:225 gp120 221:225 gp120 (from human immunodeficiency virus) 221:261 Nitrogen collisional cross sections (CCSs) of hybrid and complex glycans released from the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin were measured with a travelling-wave ion mobility mass spectrometer using dextran as the calibrant. 27477117 1 9 gly glycoproteins 202:214 arg1 ovalbumin 264:272 ovalbumin 264:272 ovalbumin 264:272 Nitrogen collisional cross sections (CCSs) of hybrid and complex glycans released from the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin were measured with a travelling-wave ion mobility mass spectrometer using dextran as the calibrant. 27477117 1 9 gly glycoproteins 202:214 arg1 glycoproteins 202:214 the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin 198:312 the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin 198:312 Nitrogen collisional cross sections (CCSs) of hybrid and complex glycans released from the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin were measured with a travelling-wave ion mobility mass spectrometer using dextran as the calibrant. 27477117 1 9 gly glycoproteins 202:214 arg1 IgG 216:218 IgG 216:218 IgG 216:218 Nitrogen collisional cross sections (CCSs) of hybrid and complex glycans released from the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin were measured with a travelling-wave ion mobility mass spectrometer using dextran as the calibrant. 27477117 1 9 gly glycoproteins 202:214 arg1 glycoprotein 283:294 α1-acid glycoprotein 275:294 α1-acid glycoprotein 275:294 Nitrogen collisional cross sections (CCSs) of hybrid and complex glycans released from the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin were measured with a travelling-wave ion mobility mass spectrometer using dextran as the calibrant. 27477117 5 10 theme transfer 1054:1061 arg1 cell 1063:1066 the transfer cell 1050:1066 the transfer cell of the Waters Synapt mass spectrometer 1050:1105 Nevertheless, in these cases, isomers could often be detected by plotting extracted fragment ATDs of diagnostic fragment ions from the negative ion CID spectra obtained in the transfer cell of the Waters Synapt mass spectrometer. 27477117 3 11 theme Man3 552:555 arg1 Fuc1 565:568 Man3 GlcNAc3 Fuc1 552:568 Man3 GlcNAc3 Fuc1 552:568 Some isomers, such as Man3 GlcNAc3 from chicken ovalbumin and Man3 GlcNAc3 Fuc1 from thyroglobulin could be partially resolved and identified by their negative ion fragmentation spectra obtained by collision-induced decomposition (CID). 27477117 9 12 theme mobility-m/z 1950:1961 arg1 lines 1969:1973 different mobility-m/z trend lines 1940:1973 different mobility-m/z trend lines 1940:1973 In addition, biantennary glycans containing a core fucose and/or a bisecting GlcNAc residue fell on different mobility-m/z trend lines to those glycans not so substituted with both of these substituents contributing to larger CCSs. 27477117 1 13 theme cross 132:136 arg1 sections 138:145 Nitrogen collisional cross sections 111:145 Nitrogen collisional cross sections (CCSs) of hybrid and complex glycans released from the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin 111:312 Nitrogen collisional cross sections (CCSs) of hybrid and complex glycans released from the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin were measured with a travelling-wave ion mobility mass spectrometer using dextran as the calibrant. 27477117 1 13 theme cross 132:136 arg1 CCSs 148:151 CCSs 148:151 CCSs 148:151 Nitrogen collisional cross sections (CCSs) of hybrid and complex glycans released from the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin were measured with a travelling-wave ion mobility mass spectrometer using dextran as the calibrant. 27477117 4 14 theme other 735:739 arg1 glycans 748:754 Several other larger glycans 727:754 Several other larger glycans 727:754 Several other larger glycans, however, although existing as isomers, produced only asymmetric rather than separated arrival time distributions (ATDs). 27477117 6 15 theme ATD 1179:1181 arg1 profile 1183:1189 an asymmetric ATD profile 1165:1189 an asymmetric ATD profile in this work 1165:1202 Coincidence in the drift times of all fragment ions with an asymmetric ATD profile in this work, and in the related earlier paper on high-mannose glycans, usually suggested that separations were because of conformers or anomers, whereas symmetrical ATDs of fragments showing differences in drift times indicated isomer separation. 27477117 3 16 from Fuc1 565:568 arg1 GlcNAc3 517:523 Man3 GlcNAc3 512:523 Man3 GlcNAc3 from chicken ovalbumin and Man3 GlcNAc3 Fuc1 from thyroglobulin 512:587 Some isomers, such as Man3 GlcNAc3 from chicken ovalbumin and Man3 GlcNAc3 Fuc1 from thyroglobulin could be partially resolved and identified by their negative ion fragmentation spectra obtained by collision-induced decomposition (CID). 27477117 6 17 theme drift 1398:1402 arg1 times 1404:1408 drift times 1398:1408 drift times 1398:1408 Coincidence in the drift times of all fragment ions with an asymmetric ATD profile in this work, and in the related earlier paper on high-mannose glycans, usually suggested that separations were because of conformers or anomers, whereas symmetrical ATDs of fragments showing differences in drift times indicated isomer separation. 27477117 7 18 theme larger 1560:1565 arg1 compounds 1567:1575 the larger compounds 1556:1575 the larger compounds 1556:1575 Although some significant differences in CCSs were found for the smaller isomeric glycans, the differences found for the larger compounds were usually too small to be analytically useful. 27477117 0 19 theme hybrid 81:86 arg1 N-glycans 100:108 hybrid and complex N-glycans 81:108 N-glycans 100:108 Travelling-wave ion mobility mass spectrometry and negative ion fragmentation of hybrid and complex N-glycans. 27477117 8 20 theme high-mannose 1787:1798 arg1 glycans 1800:1806 high-mannose glycans 1787:1806 high-mannose glycans 1787:1806 Possible correlations between CCSs and structural types were also investigated, and it was found that complex glycans tended to have slightly smaller CCSs than high-mannose glycans of comparable molecular weight. 27477117 1 21 theme hybrid 157:162 arg1 glycans 176:182 hybrid and complex glycans 157:182 glycans 176:182 Nitrogen collisional cross sections (CCSs) of hybrid and complex glycans released from the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin were measured with a travelling-wave ion mobility mass spectrometer using dextran as the calibrant. 27477117 6 22 from profile 1183:1189 arg1 work 1199:1202 this work 1194:1202 this work 1194:1202 Coincidence in the drift times of all fragment ions with an asymmetric ATD profile in this work, and in the related earlier paper on high-mannose glycans, usually suggested that separations were because of conformers or anomers, whereas symmetrical ATDs of fragments showing differences in drift times indicated isomer separation. 27477117 0 23 theme complex 92:98 arg1 N-glycans 100:108 hybrid and complex N-glycans 81:108 N-glycans 100:108 Travelling-wave ion mobility mass spectrometry and negative ion fragmentation of hybrid and complex N-glycans. 27477117 5 24 theme Waters 1075:1080 arg1 spectrometer 1094:1105 the Waters Synapt mass spectrometer 1071:1105 the Waters Synapt mass spectrometer 1071:1105 Nevertheless, in these cases, isomers could often be detected by plotting extracted fragment ATDs of diagnostic fragment ions from the negative ion CID spectra obtained in the transfer cell of the Waters Synapt mass spectrometer. 27477117 5 25 theme fragment 962:969 arg1 ATDs 971:974 extracted fragment ATDs 952:974 extracted fragment ATDs of diagnostic fragment ions from the negative ion CID spectra obtained in the transfer cell of the Waters Synapt mass spectrometer 952:1105 Nevertheless, in these cases, isomers could often be detected by plotting extracted fragment ATDs of diagnostic fragment ions from the negative ion CID spectra obtained in the transfer cell of the Waters Synapt mass spectrometer. 27477117 1 26 theme mass 364:367 arg1 spectrometer 369:380 a travelling-wave ion mobility mass spectrometer 333:380 a travelling-wave ion mobility mass spectrometer using dextran as the calibrant 333:411 Nitrogen collisional cross sections (CCSs) of hybrid and complex glycans released from the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin were measured with a travelling-wave ion mobility mass spectrometer using dextran as the calibrant. 27477117 8 27 theme molecular 1822:1830 arg1 weight 1832:1837 comparable molecular weight 1811:1837 comparable molecular weight 1811:1837 Possible correlations between CCSs and structural types were also investigated, and it was found that complex glycans tended to have slightly smaller CCSs than high-mannose glycans of comparable molecular weight. 27477117 0 28 theme Travelling-wave 0:14 arg1 spectrometry 34:45 Travelling-wave ion mobility mass spectrometry 0:45 Travelling-wave ion mobility mass spectrometry 0:45 Travelling-wave ion mobility mass spectrometry and negative ion fragmentation of hybrid and complex N-glycans. 27477117 9 29 theme larger 2059:2064 arg1 CCSs 2066:2069 larger CCSs 2059:2069 larger CCSs 2059:2069 In addition, biantennary glycans containing a core fucose and/or a bisecting GlcNAc residue fell on different mobility-m/z trend lines to those glycans not so substituted with both of these substituents contributing to larger CCSs. 27477117 3 30 from thyroglobulin 575:587 arg1 ovalbumin 538:546 chicken ovalbumin 530:546 chicken ovalbumin 530:546 Some isomers, such as Man3 GlcNAc3 from chicken ovalbumin and Man3 GlcNAc3 Fuc1 from thyroglobulin could be partially resolved and identified by their negative ion fragmentation spectra obtained by collision-induced decomposition (CID). 27477117 3 30 from thyroglobulin 575:587 arg1 Fuc1 565:568 Man3 GlcNAc3 Fuc1 552:568 Man3 GlcNAc3 Fuc1 552:568 Some isomers, such as Man3 GlcNAc3 from chicken ovalbumin and Man3 GlcNAc3 Fuc1 from thyroglobulin could be partially resolved and identified by their negative ion fragmentation spectra obtained by collision-induced decomposition (CID). 27477117 0 31 theme mobility 20:27 arg1 spectrometry 34:45 Travelling-wave ion mobility mass spectrometry 0:45 Travelling-wave ion mobility mass spectrometry 0:45 Travelling-wave ion mobility mass spectrometry and negative ion fragmentation of hybrid and complex N-glycans. 27477117 8 32 contain have 1755:1758 arg2 CCSs 1777:1780 slightly smaller CCSs 1760:1780 slightly smaller CCSs than high-mannose glycans of comparable molecular weight 1760:1837 Possible correlations between CCSs and structural types were also investigated, and it was found that complex glycans tended to have slightly smaller CCSs than high-mannose glycans of comparable molecular weight. 27477117 8 32 contain have 1755:1758 arg1 glycans 1737:1743 complex glycans 1729:1743 complex glycans 1729:1743 Possible correlations between CCSs and structural types were also investigated, and it was found that complex glycans tended to have slightly smaller CCSs than high-mannose glycans of comparable molecular weight. 27477117 1 33 theme Nitrogen 111:118 arg1 sections 138:145 Nitrogen collisional cross sections 111:145 Nitrogen collisional cross sections (CCSs) of hybrid and complex glycans released from the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin 111:312 Nitrogen collisional cross sections (CCSs) of hybrid and complex glycans released from the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin were measured with a travelling-wave ion mobility mass spectrometer using dextran as the calibrant. 27477117 1 33 theme Nitrogen 111:118 arg1 CCSs 148:151 CCSs 148:151 CCSs 148:151 Nitrogen collisional cross sections (CCSs) of hybrid and complex glycans released from the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin were measured with a travelling-wave ion mobility mass spectrometer using dextran as the calibrant. 27477117 3 34 theme ion 650:652 arg1 spectra 668:674 their negative ion fragmentation spectra 635:674 their negative ion fragmentation spectra obtained by collision-induced decomposition (CID) 635:724 Some isomers, such as Man3 GlcNAc3 from chicken ovalbumin and Man3 GlcNAc3 Fuc1 from thyroglobulin could be partially resolved and identified by their negative ion fragmentation spectra obtained by collision-induced decomposition (CID). 27477117 5 35 located detected 931:938 arg2 isomers 908:914 isomers 908:914 isomers 908:914 Nevertheless, in these cases, isomers could often be detected by plotting extracted fragment ATDs of diagnostic fragment ions from the negative ion CID spectra obtained in the transfer cell of the Waters Synapt mass spectrometer. 27477117 5 35 located detected 931:938 arg1 cases 901:905 these cases 895:905 these cases 895:905 Nevertheless, in these cases, isomers could often be detected by plotting extracted fragment ATDs of diagnostic fragment ions from the negative ion CID spectra obtained in the transfer cell of the Waters Synapt mass spectrometer. 27477117 7 36 theme smaller 1504:1510 arg1 glycans 1521:1527 the smaller isomeric glycans 1500:1527 the smaller isomeric glycans 1500:1527 Although some significant differences in CCSs were found for the smaller isomeric glycans, the differences found for the larger compounds were usually too small to be analytically useful. 27477117 5 37 theme negative 1013:1020 arg1 spectra 1030:1036 the negative ion CID spectra 1009:1036 the negative ion CID spectra obtained in the transfer cell of the Waters Synapt mass spectrometer 1009:1105 Nevertheless, in these cases, isomers could often be detected by plotting extracted fragment ATDs of diagnostic fragment ions from the negative ion CID spectra obtained in the transfer cell of the Waters Synapt mass spectrometer. 27477117 4 38 theme separated 833:841 arg1 distributions 856:868 separated arrival time distributions 833:868 only asymmetric rather than separated arrival time distributions (ATDs) 805:875 Several other larger glycans, however, although existing as isomers, produced only asymmetric rather than separated arrival time distributions (ATDs). 27477117 4 38 theme separated 833:841 arg1 ATDs 871:874 ATDs 871:874 ATDs 871:874 Several other larger glycans, however, although existing as isomers, produced only asymmetric rather than separated arrival time distributions (ATDs). 27477117 0 39 theme negative 51:58 arg1 fragmentation 64:76 negative ion fragmentation 51:76 negative ion fragmentation 51:76 Travelling-wave ion mobility mass spectrometry and negative ion fragmentation of hybrid and complex N-glycans. 27477117 5 40 theme CID 1026:1028 arg1 spectra 1030:1036 the negative ion CID spectra 1009:1036 the negative ion CID spectra obtained in the transfer cell of the Waters Synapt mass spectrometer 1009:1105 Nevertheless, in these cases, isomers could often be detected by plotting extracted fragment ATDs of diagnostic fragment ions from the negative ion CID spectra obtained in the transfer cell of the Waters Synapt mass spectrometer. 27477117 1 41 dep glycoproteins 202:214 arg1 thyroglobulin 300:312 thyroglobulin 300:312 thyroglobulin 300:312 Nitrogen collisional cross sections (CCSs) of hybrid and complex glycans released from the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin were measured with a travelling-wave ion mobility mass spectrometer using dextran as the calibrant. 27477117 1 41 dep glycoproteins 202:214 arg1 gp120 221:225 gp120 221:225 gp120 (from human immunodeficiency virus) 221:261 Nitrogen collisional cross sections (CCSs) of hybrid and complex glycans released from the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin were measured with a travelling-wave ion mobility mass spectrometer using dextran as the calibrant. 27477117 1 41 dep glycoproteins 202:214 arg1 ovalbumin 264:272 ovalbumin 264:272 ovalbumin 264:272 Nitrogen collisional cross sections (CCSs) of hybrid and complex glycans released from the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin were measured with a travelling-wave ion mobility mass spectrometer using dextran as the calibrant. 27477117 1 41 dep glycoproteins 202:214 arg1 glycoproteins 202:214 the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin 198:312 the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin 198:312 Nitrogen collisional cross sections (CCSs) of hybrid and complex glycans released from the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin were measured with a travelling-wave ion mobility mass spectrometer using dextran as the calibrant. 27477117 1 41 dep glycoproteins 202:214 arg1 IgG 216:218 IgG 216:218 IgG 216:218 Nitrogen collisional cross sections (CCSs) of hybrid and complex glycans released from the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin were measured with a travelling-wave ion mobility mass spectrometer using dextran as the calibrant. 27477117 1 41 dep glycoproteins 202:214 arg1 glycoprotein 283:294 α1-acid glycoprotein 275:294 α1-acid glycoprotein 275:294 Nitrogen collisional cross sections (CCSs) of hybrid and complex glycans released from the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin were measured with a travelling-wave ion mobility mass spectrometer using dextran as the calibrant. 27477117 8 42 theme Possible 1627:1634 arg1 correlations 1636:1647 Possible correlations 1627:1647 Possible correlations between CCSs and structural types 1627:1681 Possible correlations between CCSs and structural types were also investigated, and it was found that complex glycans tended to have slightly smaller CCSs than high-mannose glycans of comparable molecular weight. 27477117 5 43 theme fragment 990:997 arg1 ions 999:1002 diagnostic fragment ions 979:1002 diagnostic fragment ions from the negative ion CID spectra obtained in the transfer cell of the Waters Synapt mass spectrometer 979:1105 Nevertheless, in these cases, isomers could often be detected by plotting extracted fragment ATDs of diagnostic fragment ions from the negative ion CID spectra obtained in the transfer cell of the Waters Synapt mass spectrometer. 27477117 10 44 dep & 2100:2100 arg1 Sons 2102:2105 Sons 2102:2105 Sons 2102:2105 Copyright © 2016 John Wiley & Sons, Ltd. 27477117 1 45 theme complex 168:174 arg1 glycans 176:182 hybrid and complex glycans 157:182 glycans 176:182 Nitrogen collisional cross sections (CCSs) of hybrid and complex glycans released from the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin were measured with a travelling-wave ion mobility mass spectrometer using dextran as the calibrant. 27477117 6 46 from glycans 1254:1260 arg1 Coincidence 1108:1118 Coincidence 1108:1118 Coincidence in the drift times of all fragment ions with an asymmetric ATD profile in this work, and in the related earlier paper on high-mannose glycans 1108:1260 Coincidence in the drift times of all fragment ions with an asymmetric ATD profile in this work, and in the related earlier paper on high-mannose glycans, usually suggested that separations were because of conformers or anomers, whereas symmetrical ATDs of fragments showing differences in drift times indicated isomer separation. 27477117 6 47 theme symmetrical 1345:1355 arg1 ATDs 1357:1360 symmetrical ATDs 1345:1360 symmetrical ATDs of fragments showing differences in drift times 1345:1408 Coincidence in the drift times of all fragment ions with an asymmetric ATD profile in this work, and in the related earlier paper on high-mannose glycans, usually suggested that separations were because of conformers or anomers, whereas symmetrical ATDs of fragments showing differences in drift times indicated isomer separation. 27477117 1 48 theme human 233:237 arg1 virus 256:260 human immunodeficiency virus 233:260 human immunodeficiency virus 233:260 Nitrogen collisional cross sections (CCSs) of hybrid and complex glycans released from the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin were measured with a travelling-wave ion mobility mass spectrometer using dextran as the calibrant. 27477117 7 49 theme significant 1453:1463 arg1 differences 1465:1475 some significant differences 1448:1475 some significant differences in CCSs 1448:1483 Although some significant differences in CCSs were found for the smaller isomeric glycans, the differences found for the larger compounds were usually too small to be analytically useful. 27477117 3 50 theme chicken 530:536 arg1 ovalbumin 538:546 chicken ovalbumin 530:546 chicken ovalbumin 530:546 Some isomers, such as Man3 GlcNAc3 from chicken ovalbumin and Man3 GlcNAc3 Fuc1 from thyroglobulin could be partially resolved and identified by their negative ion fragmentation spectra obtained by collision-induced decomposition (CID). 27477117 6 51 theme earlier 1224:1230 arg1 paper 1232:1236 the related earlier paper 1212:1236 the related earlier paper on high-mannose glycans 1212:1260 Coincidence in the drift times of all fragment ions with an asymmetric ATD profile in this work, and in the related earlier paper on high-mannose glycans, usually suggested that separations were because of conformers or anomers, whereas symmetrical ATDs of fragments showing differences in drift times indicated isomer separation. 27477117 6 52 theme fragments 1365:1373 arg1 ATDs 1357:1360 symmetrical ATDs 1345:1360 symmetrical ATDs of fragments showing differences in drift times 1345:1408 Coincidence in the drift times of all fragment ions with an asymmetric ATD profile in this work, and in the related earlier paper on high-mannose glycans, usually suggested that separations were because of conformers or anomers, whereas symmetrical ATDs of fragments showing differences in drift times indicated isomer separation. 27477117 4 53 theme arrival 843:849 arg1 distributions 856:868 separated arrival time distributions 833:868 only asymmetric rather than separated arrival time distributions (ATDs) 805:875 Several other larger glycans, however, although existing as isomers, produced only asymmetric rather than separated arrival time distributions (ATDs). 27477117 4 53 theme arrival 843:849 arg1 ATDs 871:874 ATDs 871:874 ATDs 871:874 Several other larger glycans, however, although existing as isomers, produced only asymmetric rather than separated arrival time distributions (ATDs). 27477117 6 54 theme fragment 1146:1153 arg1 ions 1155:1158 all fragment ions 1142:1158 all fragment ions with an asymmetric ATD profile in this work 1142:1202 Coincidence in the drift times of all fragment ions with an asymmetric ATD profile in this work, and in the related earlier paper on high-mannose glycans, usually suggested that separations were because of conformers or anomers, whereas symmetrical ATDs of fragments showing differences in drift times indicated isomer separation. 27477117 3 55 theme GlcNAc3 557:563 arg1 Fuc1 565:568 Man3 GlcNAc3 Fuc1 552:568 Man3 GlcNAc3 Fuc1 552:568 Some isomers, such as Man3 GlcNAc3 from chicken ovalbumin and Man3 GlcNAc3 Fuc1 from thyroglobulin could be partially resolved and identified by their negative ion fragmentation spectra obtained by collision-induced decomposition (CID). 27477117 1 56 theme glycans 176:182 arg1 sections 138:145 Nitrogen collisional cross sections 111:145 Nitrogen collisional cross sections (CCSs) of hybrid and complex glycans released from the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin 111:312 Nitrogen collisional cross sections (CCSs) of hybrid and complex glycans released from the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin were measured with a travelling-wave ion mobility mass spectrometer using dextran as the calibrant. 27477117 1 56 theme glycans 176:182 arg1 CCSs 148:151 CCSs 148:151 CCSs 148:151 Nitrogen collisional cross sections (CCSs) of hybrid and complex glycans released from the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin were measured with a travelling-wave ion mobility mass spectrometer using dextran as the calibrant. 27477117 6 57 with ions 1155:1158 arg1 profile 1183:1189 an asymmetric ATD profile 1165:1189 an asymmetric ATD profile in this work 1165:1202 Coincidence in the drift times of all fragment ions with an asymmetric ATD profile in this work, and in the related earlier paper on high-mannose glycans, usually suggested that separations were because of conformers or anomers, whereas symmetrical ATDs of fragments showing differences in drift times indicated isomer separation. 27477117 9 58 theme GlcNAc 1917:1922 arg1 residue 1924:1930 a bisecting GlcNAc residue 1905:1930 a bisecting GlcNAc residue 1905:1930 In addition, biantennary glycans containing a core fucose and/or a bisecting GlcNAc residue fell on different mobility-m/z trend lines to those glycans not so substituted with both of these substituents contributing to larger CCSs. 27477117 1 59 from virus 256:260 arg1 thyroglobulin 300:312 thyroglobulin 300:312 thyroglobulin 300:312 Nitrogen collisional cross sections (CCSs) of hybrid and complex glycans released from the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin were measured with a travelling-wave ion mobility mass spectrometer using dextran as the calibrant. 27477117 1 59 from virus 256:260 arg1 gp120 221:225 gp120 221:225 gp120 (from human immunodeficiency virus) 221:261 Nitrogen collisional cross sections (CCSs) of hybrid and complex glycans released from the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin were measured with a travelling-wave ion mobility mass spectrometer using dextran as the calibrant. 27477117 1 59 from virus 256:260 arg1 ovalbumin 264:272 ovalbumin 264:272 ovalbumin 264:272 Nitrogen collisional cross sections (CCSs) of hybrid and complex glycans released from the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin were measured with a travelling-wave ion mobility mass spectrometer using dextran as the calibrant. 27477117 1 59 from virus 256:260 arg1 glycoproteins 202:214 the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin 198:312 the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin 198:312 Nitrogen collisional cross sections (CCSs) of hybrid and complex glycans released from the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin were measured with a travelling-wave ion mobility mass spectrometer using dextran as the calibrant. 27477117 1 59 from virus 256:260 arg1 IgG 216:218 IgG 216:218 IgG 216:218 Nitrogen collisional cross sections (CCSs) of hybrid and complex glycans released from the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin were measured with a travelling-wave ion mobility mass spectrometer using dextran as the calibrant. 27477117 1 59 from virus 256:260 arg1 glycoprotein 283:294 α1-acid glycoprotein 275:294 α1-acid glycoprotein 275:294 Nitrogen collisional cross sections (CCSs) of hybrid and complex glycans released from the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin were measured with a travelling-wave ion mobility mass spectrometer using dextran as the calibrant. 27477117 6 60 theme drift 1127:1131 arg1 times 1133:1137 the drift times 1123:1137 the drift times of all fragment ions with an asymmetric ATD profile in this work 1123:1202 Coincidence in the drift times of all fragment ions with an asymmetric ATD profile in this work, and in the related earlier paper on high-mannose glycans, usually suggested that separations were because of conformers or anomers, whereas symmetrical ATDs of fragments showing differences in drift times indicated isomer separation. 27477117 7 61 from differences 1465:1475 arg1 CCSs 1480:1483 CCSs 1480:1483 CCSs 1480:1483 Although some significant differences in CCSs were found for the smaller isomeric glycans, the differences found for the larger compounds were usually too small to be analytically useful. 27477117 9 62 theme different 1940:1948 arg1 lines 1969:1973 different mobility-m/z trend lines 1940:1973 different mobility-m/z trend lines 1940:1973 In addition, biantennary glycans containing a core fucose and/or a bisecting GlcNAc residue fell on different mobility-m/z trend lines to those glycans not so substituted with both of these substituents contributing to larger CCSs. 27477117 3 63 from ovalbumin 538:546 arg1 GlcNAc3 517:523 Man3 GlcNAc3 512:523 Man3 GlcNAc3 from chicken ovalbumin and Man3 GlcNAc3 Fuc1 from thyroglobulin 512:587 Some isomers, such as Man3 GlcNAc3 from chicken ovalbumin and Man3 GlcNAc3 Fuc1 from thyroglobulin could be partially resolved and identified by their negative ion fragmentation spectra obtained by collision-induced decomposition (CID). 27477117 8 64 theme complex 1729:1735 arg1 glycans 1737:1743 complex glycans 1729:1743 complex glycans 1729:1743 Possible correlations between CCSs and structural types were also investigated, and it was found that complex glycans tended to have slightly smaller CCSs than high-mannose glycans of comparable molecular weight. 27477117 1 65 theme collisional 120:130 arg1 sections 138:145 Nitrogen collisional cross sections 111:145 Nitrogen collisional cross sections (CCSs) of hybrid and complex glycans released from the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin 111:312 Nitrogen collisional cross sections (CCSs) of hybrid and complex glycans released from the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin were measured with a travelling-wave ion mobility mass spectrometer using dextran as the calibrant. 27477117 1 65 theme collisional 120:130 arg1 CCSs 148:151 CCSs 148:151 CCSs 148:151 Nitrogen collisional cross sections (CCSs) of hybrid and complex glycans released from the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin were measured with a travelling-wave ion mobility mass spectrometer using dextran as the calibrant. 27477117 9 66 theme trend 1963:1967 arg1 lines 1969:1973 different mobility-m/z trend lines 1940:1973 different mobility-m/z trend lines 1940:1973 In addition, biantennary glycans containing a core fucose and/or a bisecting GlcNAc residue fell on different mobility-m/z trend lines to those glycans not so substituted with both of these substituents contributing to larger CCSs. 27477117 4 67 theme Several 727:733 arg1 glycans 748:754 Several other larger glycans 727:754 Several other larger glycans 727:754 Several other larger glycans, however, although existing as isomers, produced only asymmetric rather than separated arrival time distributions (ATDs). 27477117 6 68 from differences 1383:1393 arg1 times 1404:1408 drift times 1398:1408 drift times 1398:1408 Coincidence in the drift times of all fragment ions with an asymmetric ATD profile in this work, and in the related earlier paper on high-mannose glycans, usually suggested that separations were because of conformers or anomers, whereas symmetrical ATDs of fragments showing differences in drift times indicated isomer separation. 27477117 1 69 gly glycoprotein 283:294 arg1 glycoproteins 202:214 the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin 198:312 the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin 198:312 Nitrogen collisional cross sections (CCSs) of hybrid and complex glycans released from the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin were measured with a travelling-wave ion mobility mass spectrometer using dextran as the calibrant. 27477117 1 69 gly glycoprotein 283:294 arg1 glycoprotein 283:294 α1-acid glycoprotein 275:294 α1-acid glycoprotein 275:294 Nitrogen collisional cross sections (CCSs) of hybrid and complex glycans released from the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin were measured with a travelling-wave ion mobility mass spectrometer using dextran as the calibrant. 27477117 6 70 theme asymmetric 1168:1177 arg1 profile 1183:1189 an asymmetric ATD profile 1165:1189 an asymmetric ATD profile in this work 1165:1202 Coincidence in the drift times of all fragment ions with an asymmetric ATD profile in this work, and in the related earlier paper on high-mannose glycans, usually suggested that separations were because of conformers or anomers, whereas symmetrical ATDs of fragments showing differences in drift times indicated isomer separation. 27477117 5 71 from spectra 1030:1036 arg1 ions 999:1002 diagnostic fragment ions 979:1002 diagnostic fragment ions from the negative ion CID spectra obtained in the transfer cell of the Waters Synapt mass spectrometer 979:1105 Nevertheless, in these cases, isomers could often be detected by plotting extracted fragment ATDs of diagnostic fragment ions from the negative ion CID spectra obtained in the transfer cell of the Waters Synapt mass spectrometer. 27477117 5 71 from spectra 1030:1036 arg1 ATDs 971:974 extracted fragment ATDs 952:974 extracted fragment ATDs of diagnostic fragment ions from the negative ion CID spectra obtained in the transfer cell of the Waters Synapt mass spectrometer 952:1105 Nevertheless, in these cases, isomers could often be detected by plotting extracted fragment ATDs of diagnostic fragment ions from the negative ion CID spectra obtained in the transfer cell of the Waters Synapt mass spectrometer. 27477117 8 72 theme smaller 1769:1775 arg1 CCSs 1777:1780 slightly smaller CCSs 1760:1780 slightly smaller CCSs than high-mannose glycans of comparable molecular weight 1760:1837 Possible correlations between CCSs and structural types were also investigated, and it was found that complex glycans tended to have slightly smaller CCSs than high-mannose glycans of comparable molecular weight. 27477117 1 73 theme ion 351:353 arg1 spectrometer 369:380 a travelling-wave ion mobility mass spectrometer 333:380 a travelling-wave ion mobility mass spectrometer using dextran as the calibrant 333:411 Nitrogen collisional cross sections (CCSs) of hybrid and complex glycans released from the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin were measured with a travelling-wave ion mobility mass spectrometer using dextran as the calibrant. 27477117 9 74 contain containing 1873:1882 arg2 fucose 1891:1896 a core fucose 1884:1896 a core fucose 1884:1896 In addition, biantennary glycans containing a core fucose and/or a bisecting GlcNAc residue fell on different mobility-m/z trend lines to those glycans not so substituted with both of these substituents contributing to larger CCSs. 27477117 9 74 contain containing 1873:1882 arg2 residue 1924:1930 a bisecting GlcNAc residue 1905:1930 a bisecting GlcNAc residue 1905:1930 In addition, biantennary glycans containing a core fucose and/or a bisecting GlcNAc residue fell on different mobility-m/z trend lines to those glycans not so substituted with both of these substituents contributing to larger CCSs. 27477117 9 74 contain containing 1873:1882 arg1 glycans 1865:1871 biantennary glycans 1853:1871 biantennary glycans containing a core fucose and/or a bisecting GlcNAc residue 1853:1930 In addition, biantennary glycans containing a core fucose and/or a bisecting GlcNAc residue fell on different mobility-m/z trend lines to those glycans not so substituted with both of these substituents contributing to larger CCSs. 27477117 0 75 theme N-glycans 100:108 arg1 fragmentation 64:76 negative ion fragmentation 51:76 negative ion fragmentation 51:76 Travelling-wave ion mobility mass spectrometry and negative ion fragmentation of hybrid and complex N-glycans. 27477117 0 75 theme N-glycans 100:108 arg1 spectrometry 34:45 Travelling-wave ion mobility mass spectrometry 0:45 Travelling-wave ion mobility mass spectrometry 0:45 Travelling-wave ion mobility mass spectrometry and negative ion fragmentation of hybrid and complex N-glycans. 27477117 1 76 theme travelling-wave 335:349 arg1 spectrometer 369:380 a travelling-wave ion mobility mass spectrometer 333:380 a travelling-wave ion mobility mass spectrometer using dextran as the calibrant 333:411 Nitrogen collisional cross sections (CCSs) of hybrid and complex glycans released from the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin were measured with a travelling-wave ion mobility mass spectrometer using dextran as the calibrant. 27477117 5 77 theme extracted 952:960 arg1 ATDs 971:974 extracted fragment ATDs 952:974 extracted fragment ATDs of diagnostic fragment ions from the negative ion CID spectra obtained in the transfer cell of the Waters Synapt mass spectrometer 952:1105 Nevertheless, in these cases, isomers could often be detected by plotting extracted fragment ATDs of diagnostic fragment ions from the negative ion CID spectra obtained in the transfer cell of the Waters Synapt mass spectrometer. 27477117 1 78 theme mobility 355:362 arg1 spectrometer 369:380 a travelling-wave ion mobility mass spectrometer 333:380 a travelling-wave ion mobility mass spectrometer using dextran as the calibrant 333:411 Nitrogen collisional cross sections (CCSs) of hybrid and complex glycans released from the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin were measured with a travelling-wave ion mobility mass spectrometer using dextran as the calibrant. 27477117 0 79 theme ion 16:18 arg1 spectrometry 34:45 Travelling-wave ion mobility mass spectrometry 0:45 Travelling-wave ion mobility mass spectrometry 0:45 Travelling-wave ion mobility mass spectrometry and negative ion fragmentation of hybrid and complex N-glycans. 27477117 5 80 theme spectrometer 1094:1105 arg1 cell 1063:1066 the transfer cell 1050:1066 the transfer cell of the Waters Synapt mass spectrometer 1050:1105 Nevertheless, in these cases, isomers could often be detected by plotting extracted fragment ATDs of diagnostic fragment ions from the negative ion CID spectra obtained in the transfer cell of the Waters Synapt mass spectrometer. 27477117 8 81 theme comparable 1811:1820 arg1 weight 1832:1837 comparable molecular weight 1811:1837 comparable molecular weight 1811:1837 Possible correlations between CCSs and structural types were also investigated, and it was found that complex glycans tended to have slightly smaller CCSs than high-mannose glycans of comparable molecular weight. 27477117 4 82 dep other 735:739 arg1 larger 741:746 larger 741:746 larger 741:746 Several other larger glycans, however, although existing as isomers, produced only asymmetric rather than separated arrival time distributions (ATDs). 27477117 5 83 theme Synapt 1082:1087 arg1 spectrometer 1094:1105 the Waters Synapt mass spectrometer 1071:1105 the Waters Synapt mass spectrometer 1071:1105 Nevertheless, in these cases, isomers could often be detected by plotting extracted fragment ATDs of diagnostic fragment ions from the negative ion CID spectra obtained in the transfer cell of the Waters Synapt mass spectrometer. 27477117 2 84 theme instrument 434:443 arg1 utility 418:424 The utility 414:424 The utility of this instrument for isomer separation 414:465 The utility of this instrument for isomer separation was also investigated. 27477117 0 85 theme mass 29:32 arg1 spectrometry 34:45 Travelling-wave ion mobility mass spectrometry 0:45 Travelling-wave ion mobility mass spectrometry 0:45 Travelling-wave ion mobility mass spectrometry and negative ion fragmentation of hybrid and complex N-glycans. 27477117 8 86 theme weight 1832:1837 arg1 CCSs 1777:1780 slightly smaller CCSs 1760:1780 slightly smaller CCSs than high-mannose glycans of comparable molecular weight 1760:1837 Possible correlations between CCSs and structural types were also investigated, and it was found that complex glycans tended to have slightly smaller CCSs than high-mannose glycans of comparable molecular weight. 27477117 3 87 theme negative 641:648 arg1 spectra 668:674 their negative ion fragmentation spectra 635:674 their negative ion fragmentation spectra obtained by collision-induced decomposition (CID) 635:724 Some isomers, such as Man3 GlcNAc3 from chicken ovalbumin and Man3 GlcNAc3 Fuc1 from thyroglobulin could be partially resolved and identified by their negative ion fragmentation spectra obtained by collision-induced decomposition (CID). 27477117 1 88 theme α1-acid 275:281 arg1 glycoproteins 202:214 the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin 198:312 the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin 198:312 Nitrogen collisional cross sections (CCSs) of hybrid and complex glycans released from the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin were measured with a travelling-wave ion mobility mass spectrometer using dextran as the calibrant. 27477117 1 88 theme α1-acid 275:281 arg1 glycoprotein 283:294 α1-acid glycoprotein 275:294 α1-acid glycoprotein 275:294 Nitrogen collisional cross sections (CCSs) of hybrid and complex glycans released from the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin were measured with a travelling-wave ion mobility mass spectrometer using dextran as the calibrant. 27477117 1 89 attach released 184:191 arg1 thyroglobulin 300:312 thyroglobulin 300:312 thyroglobulin 300:312 Nitrogen collisional cross sections (CCSs) of hybrid and complex glycans released from the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin were measured with a travelling-wave ion mobility mass spectrometer using dextran as the calibrant. 27477117 1 89 attach released 184:191 arg1 gp120 221:225 gp120 221:225 gp120 (from human immunodeficiency virus) 221:261 Nitrogen collisional cross sections (CCSs) of hybrid and complex glycans released from the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin were measured with a travelling-wave ion mobility mass spectrometer using dextran as the calibrant. 27477117 1 89 attach released 184:191 arg2 glycans 176:182 hybrid and complex glycans 157:182 glycans 176:182 Nitrogen collisional cross sections (CCSs) of hybrid and complex glycans released from the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin were measured with a travelling-wave ion mobility mass spectrometer using dextran as the calibrant. 27477117 1 89 attach released 184:191 arg1 ovalbumin 264:272 ovalbumin 264:272 ovalbumin 264:272 Nitrogen collisional cross sections (CCSs) of hybrid and complex glycans released from the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin were measured with a travelling-wave ion mobility mass spectrometer using dextran as the calibrant. 27477117 1 89 attach released 184:191 arg1 glycoproteins 202:214 the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin 198:312 the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin 198:312 Nitrogen collisional cross sections (CCSs) of hybrid and complex glycans released from the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin were measured with a travelling-wave ion mobility mass spectrometer using dextran as the calibrant. 27477117 1 89 attach released 184:191 arg1 IgG 216:218 IgG 216:218 IgG 216:218 Nitrogen collisional cross sections (CCSs) of hybrid and complex glycans released from the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin were measured with a travelling-wave ion mobility mass spectrometer using dextran as the calibrant. 27477117 1 89 attach released 184:191 arg1 glycoprotein 283:294 α1-acid glycoprotein 275:294 α1-acid glycoprotein 275:294 Nitrogen collisional cross sections (CCSs) of hybrid and complex glycans released from the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin were measured with a travelling-wave ion mobility mass spectrometer using dextran as the calibrant. 27477117 6 90 from Coincidence 1108:1118 arg1 times 1133:1137 the drift times 1123:1137 the drift times of all fragment ions with an asymmetric ATD profile in this work 1123:1202 Coincidence in the drift times of all fragment ions with an asymmetric ATD profile in this work, and in the related earlier paper on high-mannose glycans, usually suggested that separations were because of conformers or anomers, whereas symmetrical ATDs of fragments showing differences in drift times indicated isomer separation. 27477117 6 90 from Coincidence 1108:1118 arg1 paper 1232:1236 the related earlier paper 1212:1236 the related earlier paper on high-mannose glycans 1212:1260 Coincidence in the drift times of all fragment ions with an asymmetric ATD profile in this work, and in the related earlier paper on high-mannose glycans, usually suggested that separations were because of conformers or anomers, whereas symmetrical ATDs of fragments showing differences in drift times indicated isomer separation. 27477117 6 90 from Coincidence 1108:1118 arg1 glycans 1254:1260 high-mannose glycans 1241:1260 high-mannose glycans 1241:1260 Coincidence in the drift times of all fragment ions with an asymmetric ATD profile in this work, and in the related earlier paper on high-mannose glycans, usually suggested that separations were because of conformers or anomers, whereas symmetrical ATDs of fragments showing differences in drift times indicated isomer separation. 27477117 0 91 theme ion 60:62 arg1 fragmentation 64:76 negative ion fragmentation 51:76 negative ion fragmentation 51:76 Travelling-wave ion mobility mass spectrometry and negative ion fragmentation of hybrid and complex N-glycans. 27477117 7 92 theme isomeric 1512:1519 arg1 glycans 1521:1527 the smaller isomeric glycans 1500:1527 the smaller isomeric glycans 1500:1527 Although some significant differences in CCSs were found for the smaller isomeric glycans, the differences found for the larger compounds were usually too small to be analytically useful. 27477117 5 93 theme ion 1022:1024 arg1 spectra 1030:1036 the negative ion CID spectra 1009:1036 the negative ion CID spectra obtained in the transfer cell of the Waters Synapt mass spectrometer 1009:1105 Nevertheless, in these cases, isomers could often be detected by plotting extracted fragment ATDs of diagnostic fragment ions from the negative ion CID spectra obtained in the transfer cell of the Waters Synapt mass spectrometer. 27477117 5 94 theme mass 1089:1092 arg1 spectrometer 1094:1105 the Waters Synapt mass spectrometer 1071:1105 the Waters Synapt mass spectrometer 1071:1105 Nevertheless, in these cases, isomers could often be detected by plotting extracted fragment ATDs of diagnostic fragment ions from the negative ion CID spectra obtained in the transfer cell of the Waters Synapt mass spectrometer. 27477117 2 95 theme isomer 449:454 arg1 separation 456:465 isomer separation 449:465 isomer separation 449:465 The utility of this instrument for isomer separation was also investigated. 27477117 5 96 theme diagnostic 979:988 arg1 ions 999:1002 diagnostic fragment ions 979:1002 diagnostic fragment ions from the negative ion CID spectra obtained in the transfer cell of the Waters Synapt mass spectrometer 979:1105 Nevertheless, in these cases, isomers could often be detected by plotting extracted fragment ATDs of diagnostic fragment ions from the negative ion CID spectra obtained in the transfer cell of the Waters Synapt mass spectrometer. 27477117 3 97 theme fragmentation 654:666 arg1 spectra 668:674 their negative ion fragmentation spectra 635:674 their negative ion fragmentation spectra obtained by collision-induced decomposition (CID) 635:724 Some isomers, such as Man3 GlcNAc3 from chicken ovalbumin and Man3 GlcNAc3 Fuc1 from thyroglobulin could be partially resolved and identified by their negative ion fragmentation spectra obtained by collision-induced decomposition (CID). 27477117 3 98 theme Man3 512:515 arg1 GlcNAc3 517:523 Man3 GlcNAc3 512:523 Man3 GlcNAc3 from chicken ovalbumin and Man3 GlcNAc3 Fuc1 from thyroglobulin 512:587 Some isomers, such as Man3 GlcNAc3 from chicken ovalbumin and Man3 GlcNAc3 Fuc1 from thyroglobulin could be partially resolved and identified by their negative ion fragmentation spectra obtained by collision-induced decomposition (CID). 27477117 8 99 theme CCSs 1657:1660 arg1 types 1677:1681 CCSs and structural types 1657:1681 CCSs and structural types 1657:1681 Possible correlations between CCSs and structural types were also investigated, and it was found that complex glycans tended to have slightly smaller CCSs than high-mannose glycans of comparable molecular weight. 27477117 6 100 from paper 1232:1236 arg1 glycans 1254:1260 high-mannose glycans 1241:1260 high-mannose glycans 1241:1260 Coincidence in the drift times of all fragment ions with an asymmetric ATD profile in this work, and in the related earlier paper on high-mannose glycans, usually suggested that separations were because of conformers or anomers, whereas symmetrical ATDs of fragments showing differences in drift times indicated isomer separation. 27477117 5 101 theme ions 999:1002 arg1 ATDs 971:974 extracted fragment ATDs 952:974 extracted fragment ATDs of diagnostic fragment ions from the negative ion CID spectra obtained in the transfer cell of the Waters Synapt mass spectrometer 952:1105 Nevertheless, in these cases, isomers could often be detected by plotting extracted fragment ATDs of diagnostic fragment ions from the negative ion CID spectra obtained in the transfer cell of the Waters Synapt mass spectrometer. 27477117 8 102 theme structural 1666:1675 arg1 types 1677:1681 CCSs and structural types 1657:1681 CCSs and structural types 1657:1681 Possible correlations between CCSs and structural types were also investigated, and it was found that complex glycans tended to have slightly smaller CCSs than high-mannose glycans of comparable molecular weight. 27477117 9 103 theme biantennary 1853:1863 arg1 glycans 1865:1871 biantennary glycans 1853:1871 biantennary glycans containing a core fucose and/or a bisecting GlcNAc residue 1853:1930 In addition, biantennary glycans containing a core fucose and/or a bisecting GlcNAc residue fell on different mobility-m/z trend lines to those glycans not so substituted with both of these substituents contributing to larger CCSs. 27477117 6 104 theme isomer 1420:1425 arg1 separation 1427:1436 isomer separation 1420:1436 isomer separation 1420:1436 Coincidence in the drift times of all fragment ions with an asymmetric ATD profile in this work, and in the related earlier paper on high-mannose glycans, usually suggested that separations were because of conformers or anomers, whereas symmetrical ATDs of fragments showing differences in drift times indicated isomer separation. 27477117 5 105 from ATDs 971:974 arg1 spectra 1030:1036 the negative ion CID spectra 1009:1036 the negative ion CID spectra obtained in the transfer cell of the Waters Synapt mass spectrometer 1009:1105 Nevertheless, in these cases, isomers could often be detected by plotting extracted fragment ATDs of diagnostic fragment ions from the negative ion CID spectra obtained in the transfer cell of the Waters Synapt mass spectrometer. 26347193 0 0 theme Ratio 85:89 arg1 Quantification 9:22 Relative Quantification 0:22 Relative Quantification 0:22 Relative Quantification and Higher-Order Modeling of the Plasma Glycan Cancer Burden Ratio in Ovarian Cancer Case-Control Samples. 26347193 0 0 theme Ratio 85:89 arg1 Modeling 41:48 Higher-Order Modeling 28:48 Higher-Order Modeling 28:48 Relative Quantification and Higher-Order Modeling of the Plasma Glycan Cancer Burden Ratio in Ovarian Cancer Case-Control Samples. 26347193 6 1 theme significant 971:981 arg1 GBR 1017:1019 normalized mean GBR 1001:1019 normalized mean GBR 1001:1019 The final GBR models, built using stepwise forward regression, included three significant terms: OVC stage, normalized mean GBR, and tag chemical purity; glycan class, fucosylation, or sialylation were not significant variables. 26347193 6 1 theme significant 971:981 arg1 terms 983:987 three significant terms 965:987 three significant terms: OVC stage, normalized mean GBR, and tag chemical purity 965:1044 The final GBR models, built using stepwise forward regression, included three significant terms: OVC stage, normalized mean GBR, and tag chemical purity; glycan class, fucosylation, or sialylation were not significant variables. 26347193 6 1 theme significant 971:981 arg1 stage 994:998 OVC stage 990:998 OVC stage 990:998 The final GBR models, built using stepwise forward regression, included three significant terms: OVC stage, normalized mean GBR, and tag chemical purity; glycan class, fucosylation, or sialylation were not significant variables. 26347193 6 1 theme significant 971:981 arg1 purity 1039:1044 tag chemical purity 1026:1044 tag chemical purity 1026:1044 The final GBR models, built using stepwise forward regression, included three significant terms: OVC stage, normalized mean GBR, and tag chemical purity; glycan class, fucosylation, or sialylation were not significant variables. 26347193 5 2 theme chromatogram 822:833 arg1 abundances 835:844 the case-control extracted ion chromatogram abundances 791:844 the case-control extracted ion chromatogram abundances 791:844 Sixty-three glycan cancer burden ratios (GBRs), defined as the log10 ratio of the case-control extracted ion chromatogram abundances, were calculated above the limit of detection. 26347193 7 3 theme p 1315:1315 arg1 glycans 1272:1278 an additional four glycans 1253:1278 an additional four glycans 1253:1278 After Bonferroni correction, seven N-glycans were identified as significant (p < 0.05), and after false discovery rate correction, an additional four glycans were determined to be significant (p < 0.05), with one borderline (p = 0.05). 26347193 7 3 theme p 1315:1315 arg1 significant 1302:1312 significant 1302:1312 significant 1302:1312 After Bonferroni correction, seven N-glycans were identified as significant (p < 0.05), and after false discovery rate correction, an additional four glycans were determined to be significant (p < 0.05), with one borderline (p = 0.05). 26347193 7 3 theme p 1315:1315 arg1 < 1317:1317 p < 0.05 1315:1322 p < 0.05 1315:1322 After Bonferroni correction, seven N-glycans were identified as significant (p < 0.05), and after false discovery rate correction, an additional four glycans were determined to be significant (p < 0.05), with one borderline (p = 0.05). 26347193 8 4 theme potential 1461:1469 arg1 changes 1482:1488 potential biological changes 1461:1488 potential biological changes in OVC morphology or in host response 1461:1526 For all N-glycans, the vectors of the effects from stages II-IV were sequentially reversed, suggesting potential biological changes in OVC morphology or in host response. 26347193 0 5 theme Burden 78:83 arg1 Ratio 85:89 the Plasma Glycan Cancer Burden Ratio 53:89 the Plasma Glycan Cancer Burden Ratio 53:89 Relative Quantification and Higher-Order Modeling of the Plasma Glycan Cancer Burden Ratio in Ovarian Cancer Case-Control Samples. 26347193 0 6 from Quantification 9:22 arg1 Samples 122:128 Ovarian Cancer Case-Control Samples 94:128 Ovarian Cancer Case-Control Samples 94:128 Relative Quantification and Higher-Order Modeling of the Plasma Glycan Cancer Burden Ratio in Ovarian Cancer Case-Control Samples. 26347193 4 7 theme tags 635:638 arg1 strategy 650:657 glycan hydrazide tags (INLIGHT) strategy 618:657 glycan hydrazide tags (INLIGHT) strategy for enhanced electrospray ionization, MS/MS analysis 618:710 For relative quantitation, glycans were analyzed by the individuality normalization when labeling with glycan hydrazide tags (INLIGHT) strategy for enhanced electrospray ionization, MS/MS analysis. 26347193 0 8 theme Ovarian 94:100 arg1 Samples 122:128 Ovarian Cancer Case-Control Samples 94:128 Ovarian Cancer Case-Control Samples 94:128 Relative Quantification and Higher-Order Modeling of the Plasma Glycan Cancer Burden Ratio in Ovarian Cancer Case-Control Samples. 26347193 6 9 theme significant 1099:1109 arg1 variables 1111:1119 significant variables 1099:1119 significant variables 1099:1119 The final GBR models, built using stepwise forward regression, included three significant terms: OVC stage, normalized mean GBR, and tag chemical purity; glycan class, fucosylation, or sialylation were not significant variables. 26347193 8 10 from vectors 1381:1387 arg1 II-IV 1416:1420 stages II-IV 1409:1420 stages II-IV 1409:1420 For all N-glycans, the vectors of the effects from stages II-IV were sequentially reversed, suggesting potential biological changes in OVC morphology or in host response. 26347193 5 11 theme ion 818:820 arg1 abundances 835:844 the case-control extracted ion chromatogram abundances 791:844 the case-control extracted ion chromatogram abundances 791:844 Sixty-three glycan cancer burden ratios (GBRs), defined as the log10 ratio of the case-control extracted ion chromatogram abundances, were calculated above the limit of detection. 26347193 4 12 theme relative 519:526 arg1 quantitation 528:539 relative quantitation 519:539 relative quantitation 519:539 For relative quantitation, glycans were analyzed by the individuality normalization when labeling with glycan hydrazide tags (INLIGHT) strategy for enhanced electrospray ionization, MS/MS analysis. 26347193 4 13 theme MS/MS 697:701 arg1 ionization 685:694 enhanced electrospray ionization 663:694 enhanced electrospray ionization 663:694 For relative quantitation, glycans were analyzed by the individuality normalization when labeling with glycan hydrazide tags (INLIGHT) strategy for enhanced electrospray ionization, MS/MS analysis. 26347193 4 13 theme MS/MS 697:701 arg1 analysis 703:710 MS/MS analysis 697:710 MS/MS analysis 697:710 For relative quantitation, glycans were analyzed by the individuality normalization when labeling with glycan hydrazide tags (INLIGHT) strategy for enhanced electrospray ionization, MS/MS analysis. 26347193 1 14 dep early-stage 134:144 arg1 population-wide 147:161 population-wide 147:161 population-wide 147:161 An early-stage, population-wide biomarker for ovarian cancer (OVC) is essential to reverse its high mortality rate. 26347193 8 15 theme biological 1471:1480 arg1 changes 1482:1488 potential biological changes 1461:1488 potential biological changes in OVC morphology or in host response 1461:1526 For all N-glycans, the vectors of the effects from stages II-IV were sequentially reversed, suggesting potential biological changes in OVC morphology or in host response. 26347193 0 16 theme Case-Control 109:120 arg1 Samples 122:128 Ovarian Cancer Case-Control Samples 94:128 Ovarian Cancer Case-Control Samples 94:128 Relative Quantification and Higher-Order Modeling of the Plasma Glycan Cancer Burden Ratio in Ovarian Cancer Case-Control Samples. 26347193 8 17 from II-IV 1416:1420 arg1 vectors 1381:1387 the vectors 1377:1387 the vectors of the effects from stages II-IV 1377:1420 For all N-glycans, the vectors of the effects from stages II-IV were sequentially reversed, suggesting potential biological changes in OVC morphology or in host response. 26347193 8 17 from II-IV 1416:1420 arg1 effects 1396:1402 the effects 1392:1402 the effects from stages II-IV 1392:1420 For all N-glycans, the vectors of the effects from stages II-IV were sequentially reversed, suggesting potential biological changes in OVC morphology or in host response. 26347193 6 18 theme mean 1012:1015 arg1 GBR 1017:1019 normalized mean GBR 1001:1019 normalized mean GBR 1001:1019 The final GBR models, built using stepwise forward regression, included three significant terms: OVC stage, normalized mean GBR, and tag chemical purity; glycan class, fucosylation, or sialylation were not significant variables. 26347193 6 18 theme mean 1012:1015 arg1 terms 983:987 three significant terms 965:987 three significant terms: OVC stage, normalized mean GBR, and tag chemical purity 965:1044 The final GBR models, built using stepwise forward regression, included three significant terms: OVC stage, normalized mean GBR, and tag chemical purity; glycan class, fucosylation, or sialylation were not significant variables. 26347193 6 19 dep terms 983:987 arg1 GBR 1017:1019 normalized mean GBR 1001:1019 normalized mean GBR 1001:1019 The final GBR models, built using stepwise forward regression, included three significant terms: OVC stage, normalized mean GBR, and tag chemical purity; glycan class, fucosylation, or sialylation were not significant variables. 26347193 6 19 dep terms 983:987 arg1 terms 983:987 three significant terms 965:987 three significant terms: OVC stage, normalized mean GBR, and tag chemical purity 965:1044 The final GBR models, built using stepwise forward regression, included three significant terms: OVC stage, normalized mean GBR, and tag chemical purity; glycan class, fucosylation, or sialylation were not significant variables. 26347193 6 19 dep terms 983:987 arg1 stage 994:998 OVC stage 990:998 OVC stage 990:998 The final GBR models, built using stepwise forward regression, included three significant terms: OVC stage, normalized mean GBR, and tag chemical purity; glycan class, fucosylation, or sialylation were not significant variables. 26347193 6 19 dep terms 983:987 arg1 purity 1039:1044 tag chemical purity 1026:1044 tag chemical purity 1026:1044 The final GBR models, built using stepwise forward regression, included three significant terms: OVC stage, normalized mean GBR, and tag chemical purity; glycan class, fucosylation, or sialylation were not significant variables. 26347193 1 20 theme ovarian 177:183 arg1 OVC 193:195 OVC 193:195 OVC 193:195 An early-stage, population-wide biomarker for ovarian cancer (OVC) is essential to reverse its high mortality rate. 26347193 1 20 theme ovarian 177:183 arg1 cancer 185:190 ovarian cancer 177:190 ovarian cancer (OVC) 177:196 An early-stage, population-wide biomarker for ovarian cancer (OVC) is essential to reverse its high mortality rate. 26347193 0 21 theme Cancer 102:107 arg1 Samples 122:128 Ovarian Cancer Case-Control Samples 94:128 Ovarian Cancer Case-Control Samples 94:128 Relative Quantification and Higher-Order Modeling of the Plasma Glycan Cancer Burden Ratio in Ovarian Cancer Case-Control Samples. 26347193 5 22 theme abundances 835:844 arg1 ratio 782:786 the log10 ratio 772:786 the log10 ratio of the case-control extracted ion chromatogram abundances 772:844 Sixty-three glycan cancer burden ratios (GBRs), defined as the log10 ratio of the case-control extracted ion chromatogram abundances, were calculated above the limit of detection. 26347193 5 23 theme glycan 725:730 arg1 GBRs 754:757 GBRs 754:757 GBRs 754:757 Sixty-three glycan cancer burden ratios (GBRs), defined as the log10 ratio of the case-control extracted ion chromatogram abundances, were calculated above the limit of detection. 26347193 5 23 theme glycan 725:730 arg1 ratios 746:751 Sixty-three glycan cancer burden ratios 713:751 Sixty-three glycan cancer burden ratios (GBRs) 713:758 Sixty-three glycan cancer burden ratios (GBRs), defined as the log10 ratio of the case-control extracted ion chromatogram abundances, were calculated above the limit of detection. 26347193 6 24 theme normalized 1001:1010 arg1 GBR 1017:1019 normalized mean GBR 1001:1019 normalized mean GBR 1001:1019 The final GBR models, built using stepwise forward regression, included three significant terms: OVC stage, normalized mean GBR, and tag chemical purity; glycan class, fucosylation, or sialylation were not significant variables. 26347193 6 24 theme normalized 1001:1010 arg1 terms 983:987 three significant terms 965:987 three significant terms: OVC stage, normalized mean GBR, and tag chemical purity 965:1044 The final GBR models, built using stepwise forward regression, included three significant terms: OVC stage, normalized mean GBR, and tag chemical purity; glycan class, fucosylation, or sialylation were not significant variables. 26347193 3 25 theme plasma 429:434 arg1 samples 436:442 82 case-control plasma samples 413:442 82 case-control plasma samples 413:442 We curated a human biorepository of 82 case-control plasma samples, with 27%, 12%, 46%, and 15% falling across stages I-IV, respectively. 26347193 0 26 from Modeling 41:48 arg1 Samples 122:128 Ovarian Cancer Case-Control Samples 94:128 Ovarian Cancer Case-Control Samples 94:128 Relative Quantification and Higher-Order Modeling of the Plasma Glycan Cancer Burden Ratio in Ovarian Cancer Case-Control Samples. 26347193 7 27 theme p 1199:1199 arg1 < 1201:1201 p < 0.05 1199:1206 p < 0.05 1199:1206 After Bonferroni correction, seven N-glycans were identified as significant (p < 0.05), and after false discovery rate correction, an additional four glycans were determined to be significant (p < 0.05), with one borderline (p = 0.05). 26347193 7 28 theme Bonferroni 1128:1137 arg1 correction 1139:1148 Bonferroni correction 1128:1148 Bonferroni correction 1128:1148 After Bonferroni correction, seven N-glycans were identified as significant (p < 0.05), and after false discovery rate correction, an additional four glycans were determined to be significant (p < 0.05), with one borderline (p = 0.05). 26347193 4 29 theme electrospray 672:683 arg1 ionization 685:694 enhanced electrospray ionization 663:694 enhanced electrospray ionization 663:694 For relative quantitation, glycans were analyzed by the individuality normalization when labeling with glycan hydrazide tags (INLIGHT) strategy for enhanced electrospray ionization, MS/MS analysis. 26347193 4 29 theme electrospray 672:683 arg1 analysis 703:710 MS/MS analysis 697:710 MS/MS analysis 697:710 For relative quantitation, glycans were analyzed by the individuality normalization when labeling with glycan hydrazide tags (INLIGHT) strategy for enhanced electrospray ionization, MS/MS analysis. 26347193 6 30 theme OVC 990:992 arg1 terms 983:987 three significant terms 965:987 three significant terms: OVC stage, normalized mean GBR, and tag chemical purity 965:1044 The final GBR models, built using stepwise forward regression, included three significant terms: OVC stage, normalized mean GBR, and tag chemical purity; glycan class, fucosylation, or sialylation were not significant variables. 26347193 6 30 theme OVC 990:992 arg1 stage 994:998 OVC stage 990:998 OVC stage 990:998 The final GBR models, built using stepwise forward regression, included three significant terms: OVC stage, normalized mean GBR, and tag chemical purity; glycan class, fucosylation, or sialylation were not significant variables. 26347193 0 31 theme Relative 0:7 arg1 Quantification 9:22 Relative Quantification 0:22 Relative Quantification 0:22 Relative Quantification and Higher-Order Modeling of the Plasma Glycan Cancer Burden Ratio in Ovarian Cancer Case-Control Samples. 26347193 6 32 theme GBR 903:905 arg1 models 907:912 The final GBR models 893:912 The final GBR models 893:912 The final GBR models, built using stepwise forward regression, included three significant terms: OVC stage, normalized mean GBR, and tag chemical purity; glycan class, fucosylation, or sialylation were not significant variables. 26347193 4 33 theme enhanced 663:670 arg1 ionization 685:694 enhanced electrospray ionization 663:694 enhanced electrospray ionization 663:694 For relative quantitation, glycans were analyzed by the individuality normalization when labeling with glycan hydrazide tags (INLIGHT) strategy for enhanced electrospray ionization, MS/MS analysis. 26347193 4 33 theme enhanced 663:670 arg1 analysis 703:710 MS/MS analysis 697:710 MS/MS analysis 697:710 For relative quantitation, glycans were analyzed by the individuality normalization when labeling with glycan hydrazide tags (INLIGHT) strategy for enhanced electrospray ionization, MS/MS analysis. 26347193 2 34 theme high 359:362 arg1 specificity 364:374 sufficiently high specificity 346:374 sufficiently high specificity 346:374 Aberrant glycosylation by OVC has been reported, but studies have yet to identify an N-glycan with sufficiently high specificity. 26347193 0 35 theme Higher-Order 28:39 arg1 Modeling 41:48 Higher-Order Modeling 28:48 Higher-Order Modeling 28:48 Relative Quantification and Higher-Order Modeling of the Plasma Glycan Cancer Burden Ratio in Ovarian Cancer Case-Control Samples. 26347193 6 36 theme final 897:901 arg1 models 907:912 The final GBR models 893:912 The final GBR models 893:912 The final GBR models, built using stepwise forward regression, included three significant terms: OVC stage, normalized mean GBR, and tag chemical purity; glycan class, fucosylation, or sialylation were not significant variables. 26347193 5 37 theme burden 739:744 arg1 GBRs 754:757 GBRs 754:757 GBRs 754:757 Sixty-three glycan cancer burden ratios (GBRs), defined as the log10 ratio of the case-control extracted ion chromatogram abundances, were calculated above the limit of detection. 26347193 5 37 theme burden 739:744 arg1 ratios 746:751 Sixty-three glycan cancer burden ratios 713:751 Sixty-three glycan cancer burden ratios (GBRs) 713:758 Sixty-three glycan cancer burden ratios (GBRs), defined as the log10 ratio of the case-control extracted ion chromatogram abundances, were calculated above the limit of detection. 26347193 7 38 dep significant 1186:1196 arg1 < 1201:1201 p < 0.05 1199:1206 p < 0.05 1199:1206 After Bonferroni correction, seven N-glycans were identified as significant (p < 0.05), and after false discovery rate correction, an additional four glycans were determined to be significant (p < 0.05), with one borderline (p = 0.05). 26347193 5 39 theme detection 882:890 arg1 limit 873:877 the limit 869:877 the limit of detection 869:890 Sixty-three glycan cancer burden ratios (GBRs), defined as the log10 ratio of the case-control extracted ion chromatogram abundances, were calculated above the limit of detection. 26347193 5 40 theme extracted 808:816 arg1 abundances 835:844 the case-control extracted ion chromatogram abundances 791:844 the case-control extracted ion chromatogram abundances 791:844 Sixty-three glycan cancer burden ratios (GBRs), defined as the log10 ratio of the case-control extracted ion chromatogram abundances, were calculated above the limit of detection. 26347193 3 41 theme human 390:394 arg1 biorepository 396:408 a human biorepository 388:408 a human biorepository of 82 case-control plasma samples 388:442 We curated a human biorepository of 82 case-control plasma samples, with 27%, 12%, 46%, and 15% falling across stages I-IV, respectively. 26347193 8 42 theme stages 1409:1414 arg1 II-IV 1416:1420 stages II-IV 1409:1420 stages II-IV 1409:1420 For all N-glycans, the vectors of the effects from stages II-IV were sequentially reversed, suggesting potential biological changes in OVC morphology or in host response. 26347193 4 43 theme individuality 571:583 arg1 normalization 585:597 the individuality normalization 567:597 the individuality normalization 567:597 For relative quantitation, glycans were analyzed by the individuality normalization when labeling with glycan hydrazide tags (INLIGHT) strategy for enhanced electrospray ionization, MS/MS analysis. 26347193 5 44 theme case-control 795:806 arg1 abundances 835:844 the case-control extracted ion chromatogram abundances 791:844 the case-control extracted ion chromatogram abundances 791:844 Sixty-three glycan cancer burden ratios (GBRs), defined as the log10 ratio of the case-control extracted ion chromatogram abundances, were calculated above the limit of detection. 26347193 3 45 theme samples 436:442 arg1 biorepository 396:408 a human biorepository 388:408 a human biorepository of 82 case-control plasma samples 388:442 We curated a human biorepository of 82 case-control plasma samples, with 27%, 12%, 46%, and 15% falling across stages I-IV, respectively. 26347193 3 46 theme case-control 416:427 arg1 samples 436:442 82 case-control plasma samples 413:442 82 case-control plasma samples 413:442 We curated a human biorepository of 82 case-control plasma samples, with 27%, 12%, 46%, and 15% falling across stages I-IV, respectively. 26347193 5 47 theme cancer 732:737 arg1 GBRs 754:757 GBRs 754:757 GBRs 754:757 Sixty-three glycan cancer burden ratios (GBRs), defined as the log10 ratio of the case-control extracted ion chromatogram abundances, were calculated above the limit of detection. 26347193 5 47 theme cancer 732:737 arg1 ratios 746:751 Sixty-three glycan cancer burden ratios 713:751 Sixty-three glycan cancer burden ratios (GBRs) 713:758 Sixty-three glycan cancer burden ratios (GBRs), defined as the log10 ratio of the case-control extracted ion chromatogram abundances, were calculated above the limit of detection. 26347193 6 48 theme forward 936:942 arg1 regression 944:953 stepwise forward regression 927:953 stepwise forward regression 927:953 The final GBR models, built using stepwise forward regression, included three significant terms: OVC stage, normalized mean GBR, and tag chemical purity; glycan class, fucosylation, or sialylation were not significant variables. 26347193 5 49 theme log10 776:780 arg1 ratio 782:786 the log10 ratio 772:786 the log10 ratio of the case-control extracted ion chromatogram abundances 772:844 Sixty-three glycan cancer burden ratios (GBRs), defined as the log10 ratio of the case-control extracted ion chromatogram abundances, were calculated above the limit of detection. 26347193 0 50 theme Plasma 57:62 arg1 Ratio 85:89 the Plasma Glycan Cancer Burden Ratio 53:89 the Plasma Glycan Cancer Burden Ratio 53:89 Relative Quantification and Higher-Order Modeling of the Plasma Glycan Cancer Burden Ratio in Ovarian Cancer Case-Control Samples. 26347193 8 51 theme effects 1396:1402 arg1 vectors 1381:1387 the vectors 1377:1387 the vectors of the effects from stages II-IV 1377:1420 For all N-glycans, the vectors of the effects from stages II-IV were sequentially reversed, suggesting potential biological changes in OVC morphology or in host response. 26347193 8 52 from changes 1482:1488 arg1 morphology 1497:1506 OVC morphology 1493:1506 OVC morphology 1493:1506 For all N-glycans, the vectors of the effects from stages II-IV were sequentially reversed, suggesting potential biological changes in OVC morphology or in host response. 26347193 8 52 from changes 1482:1488 arg1 response 1519:1526 host response 1514:1526 host response 1514:1526 For all N-glycans, the vectors of the effects from stages II-IV were sequentially reversed, suggesting potential biological changes in OVC morphology or in host response. 26347193 7 53 dep significant 1302:1312 arg1 glycans 1272:1278 an additional four glycans 1253:1278 an additional four glycans 1253:1278 After Bonferroni correction, seven N-glycans were identified as significant (p < 0.05), and after false discovery rate correction, an additional four glycans were determined to be significant (p < 0.05), with one borderline (p = 0.05). 26347193 7 53 dep significant 1302:1312 arg1 significant 1302:1312 significant 1302:1312 significant 1302:1312 After Bonferroni correction, seven N-glycans were identified as significant (p < 0.05), and after false discovery rate correction, an additional four glycans were determined to be significant (p < 0.05), with one borderline (p = 0.05). 26347193 7 53 dep significant 1302:1312 arg1 < 1317:1317 p < 0.05 1315:1322 p < 0.05 1315:1322 After Bonferroni correction, seven N-glycans were identified as significant (p < 0.05), and after false discovery rate correction, an additional four glycans were determined to be significant (p < 0.05), with one borderline (p = 0.05). 26347193 2 54 with N-glycan 332:339 arg1 specificity 364:374 sufficiently high specificity 346:374 sufficiently high specificity 346:374 Aberrant glycosylation by OVC has been reported, but studies have yet to identify an N-glycan with sufficiently high specificity. 26347193 7 55 theme additional 1256:1265 arg1 < 1317:1317 p < 0.05 1315:1322 p < 0.05 1315:1322 After Bonferroni correction, seven N-glycans were identified as significant (p < 0.05), and after false discovery rate correction, an additional four glycans were determined to be significant (p < 0.05), with one borderline (p = 0.05). 26347193 7 55 theme additional 1256:1265 arg1 significant 1302:1312 significant 1302:1312 significant 1302:1312 After Bonferroni correction, seven N-glycans were identified as significant (p < 0.05), and after false discovery rate correction, an additional four glycans were determined to be significant (p < 0.05), with one borderline (p = 0.05). 26347193 7 55 theme additional 1256:1265 arg1 glycans 1272:1278 an additional four glycans 1253:1278 an additional four glycans 1253:1278 After Bonferroni correction, seven N-glycans were identified as significant (p < 0.05), and after false discovery rate correction, an additional four glycans were determined to be significant (p < 0.05), with one borderline (p = 0.05). 26347193 6 56 theme chemical 1030:1037 arg1 terms 983:987 three significant terms 965:987 three significant terms: OVC stage, normalized mean GBR, and tag chemical purity 965:1044 The final GBR models, built using stepwise forward regression, included three significant terms: OVC stage, normalized mean GBR, and tag chemical purity; glycan class, fucosylation, or sialylation were not significant variables. 26347193 6 56 theme chemical 1030:1037 arg1 purity 1039:1044 tag chemical purity 1026:1044 tag chemical purity 1026:1044 The final GBR models, built using stepwise forward regression, included three significant terms: OVC stage, normalized mean GBR, and tag chemical purity; glycan class, fucosylation, or sialylation were not significant variables. 26347193 8 57 theme OVC 1493:1495 arg1 morphology 1497:1506 OVC morphology 1493:1506 OVC morphology 1493:1506 For all N-glycans, the vectors of the effects from stages II-IV were sequentially reversed, suggesting potential biological changes in OVC morphology or in host response. 26347193 7 58 theme rate 1236:1239 arg1 correction 1241:1250 false discovery rate correction 1220:1250 false discovery rate correction 1220:1250 After Bonferroni correction, seven N-glycans were identified as significant (p < 0.05), and after false discovery rate correction, an additional four glycans were determined to be significant (p < 0.05), with one borderline (p = 0.05). 26347193 4 59 theme glycan 618:623 arg1 tags 635:638 glycan hydrazide tags 618:638 glycan hydrazide tags (INLIGHT) strategy for enhanced electrospray ionization, MS/MS analysis 618:710 For relative quantitation, glycans were analyzed by the individuality normalization when labeling with glycan hydrazide tags (INLIGHT) strategy for enhanced electrospray ionization, MS/MS analysis. 26347193 4 59 theme glycan 618:623 arg1 INLIGHT 641:647 INLIGHT 641:647 INLIGHT 641:647 For relative quantitation, glycans were analyzed by the individuality normalization when labeling with glycan hydrazide tags (INLIGHT) strategy for enhanced electrospray ionization, MS/MS analysis. 26347193 6 60 theme tag 1026:1028 arg1 terms 983:987 three significant terms 965:987 three significant terms: OVC stage, normalized mean GBR, and tag chemical purity 965:1044 The final GBR models, built using stepwise forward regression, included three significant terms: OVC stage, normalized mean GBR, and tag chemical purity; glycan class, fucosylation, or sialylation were not significant variables. 26347193 6 60 theme tag 1026:1028 arg1 purity 1039:1044 tag chemical purity 1026:1044 tag chemical purity 1026:1044 The final GBR models, built using stepwise forward regression, included three significant terms: OVC stage, normalized mean GBR, and tag chemical purity; glycan class, fucosylation, or sialylation were not significant variables. 26347193 6 61 theme glycan 1047:1052 arg1 class 1054:1058 glycan class 1047:1058 glycan class 1047:1058 The final GBR models, built using stepwise forward regression, included three significant terms: OVC stage, normalized mean GBR, and tag chemical purity; glycan class, fucosylation, or sialylation were not significant variables. 26347193 7 62 theme = 1349:1349 arg1 borderline 1335:1344 borderline 1335:1344 borderline 1335:1344 After Bonferroni correction, seven N-glycans were identified as significant (p < 0.05), and after false discovery rate correction, an additional four glycans were determined to be significant (p < 0.05), with one borderline (p = 0.05). 26347193 7 62 theme = 1349:1349 arg1 p 1347:1347 p = 0.05 1347:1354 p = 0.05 1347:1354 After Bonferroni correction, seven N-glycans were identified as significant (p < 0.05), and after false discovery rate correction, an additional four glycans were determined to be significant (p < 0.05), with one borderline (p = 0.05). 26347193 2 63 theme Aberrant 247:254 arg1 glycosylation 256:268 Aberrant glycosylation 247:268 Aberrant glycosylation by OVC 247:275 Aberrant glycosylation by OVC has been reported, but studies have yet to identify an N-glycan with sufficiently high specificity. 26347193 5 64 theme Sixty-three 713:723 arg1 GBRs 754:757 GBRs 754:757 GBRs 754:757 Sixty-three glycan cancer burden ratios (GBRs), defined as the log10 ratio of the case-control extracted ion chromatogram abundances, were calculated above the limit of detection. 26347193 5 64 theme Sixty-three 713:723 arg1 ratios 746:751 Sixty-three glycan cancer burden ratios 713:751 Sixty-three glycan cancer burden ratios (GBRs) 713:758 Sixty-three glycan cancer burden ratios (GBRs), defined as the log10 ratio of the case-control extracted ion chromatogram abundances, were calculated above the limit of detection. 26347193 1 65 theme early-stage 134:144 arg1 essential 201:209 essential 201:209 essential 201:209 An early-stage, population-wide biomarker for ovarian cancer (OVC) is essential to reverse its high mortality rate. 26347193 1 65 theme early-stage 134:144 arg1 biomarker 163:171 An early-stage, population-wide biomarker 131:171 An early-stage, population-wide biomarker for ovarian cancer (OVC) 131:196 An early-stage, population-wide biomarker for ovarian cancer (OVC) is essential to reverse its high mortality rate. 26347193 0 66 theme Cancer 71:76 arg1 Ratio 85:89 the Plasma Glycan Cancer Burden Ratio 53:89 the Plasma Glycan Cancer Burden Ratio 53:89 Relative Quantification and Higher-Order Modeling of the Plasma Glycan Cancer Burden Ratio in Ovarian Cancer Case-Control Samples. 26347193 7 67 theme discovery 1226:1234 arg1 rate 1236:1239 false discovery rate 1220:1239 false discovery rate correction 1220:1250 After Bonferroni correction, seven N-glycans were identified as significant (p < 0.05), and after false discovery rate correction, an additional four glycans were determined to be significant (p < 0.05), with one borderline (p = 0.05). 26347193 4 68 theme hydrazide 625:633 arg1 tags 635:638 glycan hydrazide tags 618:638 glycan hydrazide tags (INLIGHT) strategy for enhanced electrospray ionization, MS/MS analysis 618:710 For relative quantitation, glycans were analyzed by the individuality normalization when labeling with glycan hydrazide tags (INLIGHT) strategy for enhanced electrospray ionization, MS/MS analysis. 26347193 4 68 theme hydrazide 625:633 arg1 INLIGHT 641:647 INLIGHT 641:647 INLIGHT 641:647 For relative quantitation, glycans were analyzed by the individuality normalization when labeling with glycan hydrazide tags (INLIGHT) strategy for enhanced electrospray ionization, MS/MS analysis. 26347193 7 69 theme false 1220:1224 arg1 rate 1236:1239 false discovery rate 1220:1239 false discovery rate correction 1220:1250 After Bonferroni correction, seven N-glycans were identified as significant (p < 0.05), and after false discovery rate correction, an additional four glycans were determined to be significant (p < 0.05), with one borderline (p = 0.05). 26347193 1 70 theme high 226:229 arg1 rate 241:244 its high mortality rate 222:244 its high mortality rate 222:244 An early-stage, population-wide biomarker for ovarian cancer (OVC) is essential to reverse its high mortality rate. 26347193 0 71 theme Glycan 64:69 arg1 Ratio 85:89 the Plasma Glycan Cancer Burden Ratio 53:89 the Plasma Glycan Cancer Burden Ratio 53:89 Relative Quantification and Higher-Order Modeling of the Plasma Glycan Cancer Burden Ratio in Ovarian Cancer Case-Control Samples. 26347193 6 72 theme stepwise 927:934 arg1 regression 944:953 stepwise forward regression 927:953 stepwise forward regression 927:953 The final GBR models, built using stepwise forward regression, included three significant terms: OVC stage, normalized mean GBR, and tag chemical purity; glycan class, fucosylation, or sialylation were not significant variables. 26347193 3 73 dep stages 488:493 arg1 I-IV 495:498 I-IV 495:498 I-IV 495:498 We curated a human biorepository of 82 case-control plasma samples, with 27%, 12%, 46%, and 15% falling across stages I-IV, respectively. 26347193 8 74 theme host 1514:1517 arg1 response 1519:1526 host response 1514:1526 host response 1514:1526 For all N-glycans, the vectors of the effects from stages II-IV were sequentially reversed, suggesting potential biological changes in OVC morphology or in host response. 26347193 1 75 theme mortality 231:239 arg1 rate 241:244 its high mortality rate 222:244 its high mortality rate 222:244 An early-stage, population-wide biomarker for ovarian cancer (OVC) is essential to reverse its high mortality rate. 27913144 8 0 with interaction 1006:1016 arg1 Trn1 1023:1026 Trn1 1023:1026 Trn1 1023:1026 Whereas enhanced O-GlcNAcylation increased hnRNP A1 interaction with Trn1, enhanced phosphorylation reduced the interaction between the proteins. 27913144 5 1 theme C-terminal 645:654 arg1 domain 656:661 hnRNP A1 C-terminal domain 636:661 hnRNP A1 C-terminal domain 636:661 Moreover, phosphorylation of serine residues at hnRNP A1 C-terminal domain affects its translocation. 27913144 11 2 from transcription 1557:1569 arg1 regulation 1504:1513 the regulation 1500:1513 the regulation of the specific activities of hnRNP A1 in transcription and translation 1500:1585 There is a need for further study, to elucidate the role of O-GlcNAcylation in the regulation of the specific activities of hnRNP A1 in transcription and translation. 27913144 7 3 theme phosphorylation 907:921 arg1 sites 923:927 Several putative novel O-GlcNAcylation and phosphorylation sites 864:927 sites 923:927 Several putative novel O-GlcNAcylation and phosphorylation sites in hnRNP A1 were mapped. 27913144 6 4 link O-linked 798:805 arg1 O-GlcNAcylation 834:848 O-GlcNAcylation 834:848 O-GlcNAcylation 834:848 In this study, we found that phosphorylation is not the only modification that hnRNP A1 undergoes, but also O-linked N-acetylglucosaminylation (O-GlcNAcylation) could occur. 27913144 6 4 link O-linked 798:805 arg1 N-acetylglucosaminylation 807:831 O-linked N-acetylglucosaminylation 798:831 also O-linked N-acetylglucosaminylation (O-GlcNAcylation) 793:849 In this study, we found that phosphorylation is not the only modification that hnRNP A1 undergoes, but also O-linked N-acetylglucosaminylation (O-GlcNAcylation) could occur. 27913144 0 5 from effect 4:9 arg1 interaction 60:70 interaction 60:70 interaction with transportin1 60:88 The effect of O-GlcNAcylation on hnRNP A1 translocation and interaction with transportin1. 27913144 0 5 from effect 4:9 arg1 translocation 42:54 hnRNP A1 translocation 33:54 hnRNP A1 translocation 33:54 The effect of O-GlcNAcylation on hnRNP A1 translocation and interaction with transportin1. 27913144 7 6 theme novel 881:885 arg1 O-GlcNAcylation 887:901 Several putative novel O-GlcNAcylation and phosphorylation sites 864:927 O-GlcNAcylation 887:901 Several putative novel O-GlcNAcylation and phosphorylation sites in hnRNP A1 were mapped. 27913144 11 7 theme further 1441:1447 arg1 study 1449:1453 further study 1441:1453 further study 1441:1453 There is a need for further study, to elucidate the role of O-GlcNAcylation in the regulation of the specific activities of hnRNP A1 in transcription and translation. 27913144 6 8 theme O-linked 798:805 arg1 O-GlcNAcylation 834:848 O-GlcNAcylation 834:848 O-GlcNAcylation 834:848 In this study, we found that phosphorylation is not the only modification that hnRNP A1 undergoes, but also O-linked N-acetylglucosaminylation (O-GlcNAcylation) could occur. 27913144 6 8 theme O-linked 798:805 arg1 N-acetylglucosaminylation 807:831 O-linked N-acetylglucosaminylation 798:831 also O-linked N-acetylglucosaminylation (O-GlcNAcylation) 793:849 In this study, we found that phosphorylation is not the only modification that hnRNP A1 undergoes, but also O-linked N-acetylglucosaminylation (O-GlcNAcylation) could occur. 27913144 10 9 theme new 1293:1295 arg1 player 1297:1302 a new player 1291:1302 a new player 1291:1302 These findings suggest that a new player, i.e., O-GlcNAcylation, regulates hnRNP A1 translocation and interaction with Trn1, possibly affecting its function. 27913144 10 10 dep O-GlcNAcylation 1311:1325 arg1 i.e. 1305:1308 i.e. 1305:1308 i.e. 1305:1308 These findings suggest that a new player, i.e., O-GlcNAcylation, regulates hnRNP A1 translocation and interaction with Trn1, possibly affecting its function. 27913144 11 11 from activities 1531:1540 arg1 transcription 1557:1569 transcription 1557:1569 transcription 1557:1569 There is a need for further study, to elucidate the role of O-GlcNAcylation in the regulation of the specific activities of hnRNP A1 in transcription and translation. 27913144 11 11 from activities 1531:1540 arg1 translation 1575:1585 translation 1575:1585 translation 1575:1585 There is a need for further study, to elucidate the role of O-GlcNAcylation in the regulation of the specific activities of hnRNP A1 in transcription and translation. 27913144 0 12 with interaction 60:70 arg1 transportin1 77:88 transportin1 77:88 transportin1 77:88 The effect of O-GlcNAcylation on hnRNP A1 translocation and interaction with transportin1. 27913144 7 13 from O-GlcNAcylation 887:901 arg1 A1 938:939 hnRNP A1 932:939 hnRNP A1 932:939 Several putative novel O-GlcNAcylation and phosphorylation sites in hnRNP A1 were mapped. 27913144 7 14 theme Several 864:870 arg1 O-GlcNAcylation 887:901 Several putative novel O-GlcNAcylation and phosphorylation sites 864:927 O-GlcNAcylation 887:901 Several putative novel O-GlcNAcylation and phosphorylation sites in hnRNP A1 were mapped. 27913144 2 15 theme anchored 338:345 arg1 pre-mRNA 347:354 its anchored pre-mRNA 334:354 its anchored pre-mRNA for further processing 334:377 Although predominantly nuclear, hnRNP A1 shuttles rapidly between the nucleus and the cytosol, delivering its anchored pre-mRNA for further processing. 27913144 5 16 theme residues 624:631 arg1 phosphorylation 598:612 phosphorylation 598:612 phosphorylation of serine residues at hnRNP A1 C-terminal domain 598:661 Moreover, phosphorylation of serine residues at hnRNP A1 C-terminal domain affects its translocation. 27913144 5 17 theme serine 617:622 arg1 residues 624:631 serine residues 617:631 serine residues 617:631 Moreover, phosphorylation of serine residues at hnRNP A1 C-terminal domain affects its translocation. 27913144 7 18 theme putative 872:879 arg1 O-GlcNAcylation 887:901 Several putative novel O-GlcNAcylation and phosphorylation sites 864:927 O-GlcNAcylation 887:901 Several putative novel O-GlcNAcylation and phosphorylation sites in hnRNP A1 were mapped. 27913144 1 19 theme major 154:158 arg1 protein 177:183 a major pre-mRNA binding protein 152:183 a major pre-mRNA binding protein involved in transcription and translation 152:225 The heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is a major pre-mRNA binding protein involved in transcription and translation. 27913144 1 19 theme major 154:158 arg1 A1 135:136 The heterogeneous nuclear ribonucleoprotein A1 91:136 The heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) 91:147 The heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is a major pre-mRNA binding protein involved in transcription and translation. 27913144 0 20 theme A1 39:40 arg1 translocation 42:54 hnRNP A1 translocation 33:54 hnRNP A1 translocation 33:54 The effect of O-GlcNAcylation on hnRNP A1 translocation and interaction with transportin1. 27913144 8 21 theme enhanced 1029:1036 arg1 phosphorylation 1038:1052 enhanced phosphorylation 1029:1052 enhanced phosphorylation 1029:1052 Whereas enhanced O-GlcNAcylation increased hnRNP A1 interaction with Trn1, enhanced phosphorylation reduced the interaction between the proteins. 27913144 1 22 theme pre-mRNA 160:167 arg1 protein 177:183 a major pre-mRNA binding protein 152:183 a major pre-mRNA binding protein involved in transcription and translation 152:225 The heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is a major pre-mRNA binding protein involved in transcription and translation. 27913144 1 22 theme pre-mRNA 160:167 arg1 A1 135:136 The heterogeneous nuclear ribonucleoprotein A1 91:136 The heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) 91:147 The heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is a major pre-mRNA binding protein involved in transcription and translation. 27913144 5 23 theme hnRNP 636:640 arg1 domain 656:661 hnRNP A1 C-terminal domain 636:661 hnRNP A1 C-terminal domain 636:661 Moreover, phosphorylation of serine residues at hnRNP A1 C-terminal domain affects its translocation. 27913144 10 24 theme A1 1344:1345 arg1 translocation 1347:1359 hnRNP A1 translocation 1338:1359 hnRNP A1 translocation 1338:1359 These findings suggest that a new player, i.e., O-GlcNAcylation, regulates hnRNP A1 translocation and interaction with Trn1, possibly affecting its function. 27913144 7 25 from sites 923:927 arg1 A1 938:939 hnRNP A1 932:939 hnRNP A1 932:939 Several putative novel O-GlcNAcylation and phosphorylation sites in hnRNP A1 were mapped. 27913144 1 26 theme binding 169:175 arg1 protein 177:183 a major pre-mRNA binding protein 152:183 a major pre-mRNA binding protein involved in transcription and translation 152:225 The heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is a major pre-mRNA binding protein involved in transcription and translation. 27913144 1 26 theme binding 169:175 arg1 A1 135:136 The heterogeneous nuclear ribonucleoprotein A1 91:136 The heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) 91:147 The heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is a major pre-mRNA binding protein involved in transcription and translation. 27913144 10 27 with interaction 1365:1375 arg1 Trn1 1382:1385 Trn1 1382:1385 Trn1 1382:1385 These findings suggest that a new player, i.e., O-GlcNAcylation, regulates hnRNP A1 translocation and interaction with Trn1, possibly affecting its function. 27913144 4 28 theme A1 564:565 arg1 translocation 541:553 the translocation 537:553 the translocation of hnRNP A1 back to the nucleus 537:585 Transportin1 (Trn1), a translocation protein, facilitates the translocation of hnRNP A1 back to the nucleus. 27913144 5 29 theme A1 642:643 arg1 domain 656:661 hnRNP A1 C-terminal domain 636:661 hnRNP A1 C-terminal domain 636:661 Moreover, phosphorylation of serine residues at hnRNP A1 C-terminal domain affects its translocation. 27913144 11 30 from regulation 1504:1513 arg1 transcription 1557:1569 transcription 1557:1569 transcription 1557:1569 There is a need for further study, to elucidate the role of O-GlcNAcylation in the regulation of the specific activities of hnRNP A1 in transcription and translation. 27913144 11 30 from regulation 1504:1513 arg1 translation 1575:1585 translation 1575:1585 translation 1575:1585 There is a need for further study, to elucidate the role of O-GlcNAcylation in the regulation of the specific activities of hnRNP A1 in transcription and translation. 27913144 11 31 theme O-GlcNAcylation 1481:1495 arg1 role 1473:1476 the role 1469:1476 the role of O-GlcNAcylation in the regulation of the specific activities of hnRNP A1 in transcription and translation 1469:1585 There is a need for further study, to elucidate the role of O-GlcNAcylation in the regulation of the specific activities of hnRNP A1 in transcription and translation. 27913144 11 32 from translation 1575:1585 arg1 regulation 1504:1513 the regulation 1500:1513 the regulation of the specific activities of hnRNP A1 in transcription and translation 1500:1585 There is a need for further study, to elucidate the role of O-GlcNAcylation in the regulation of the specific activities of hnRNP A1 in transcription and translation. 27913144 0 33 theme O-GlcNAcylation 14:28 arg1 effect 4:9 The effect 0:9 The effect of O-GlcNAcylation on hnRNP A1 translocation and interaction with transportin1. 0:89 The effect of O-GlcNAcylation on hnRNP A1 translocation and interaction with transportin1. 27913144 4 34 theme hnRNP 558:562 arg1 A1 564:565 hnRNP A1 558:565 hnRNP A1 558:565 Transportin1 (Trn1), a translocation protein, facilitates the translocation of hnRNP A1 back to the nucleus. 27913144 6 35 theme hnRNP 769:773 arg1 A1 775:776 hnRNP A1 769:776 hnRNP A1 769:776 In this study, we found that phosphorylation is not the only modification that hnRNP A1 undergoes, but also O-linked N-acetylglucosaminylation (O-GlcNAcylation) could occur. 27913144 1 36 theme heterogeneous 95:107 arg1 protein 177:183 a major pre-mRNA binding protein 152:183 a major pre-mRNA binding protein involved in transcription and translation 152:225 The heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is a major pre-mRNA binding protein involved in transcription and translation. 27913144 1 36 theme heterogeneous 95:107 arg1 A1 135:136 The heterogeneous nuclear ribonucleoprotein A1 91:136 The heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) 91:147 The heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is a major pre-mRNA binding protein involved in transcription and translation. 27913144 1 36 theme heterogeneous 95:107 arg1 A1 145:146 hnRNP A1 139:146 hnRNP A1 139:146 The heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is a major pre-mRNA binding protein involved in transcription and translation. 27913144 9 37 theme hnRNP 1150:1154 arg1 A1 1156:1157 hnRNP A1 1150:1157 hnRNP A1 seclusion in the nucleus 1150:1182 In addition, elevated O-GlcNAcylation resulted in hnRNP A1 seclusion in the nucleus, whereas elevated phosphorylation resulted in its accumulation in the cytosol. 27913144 9 38 theme elevated 1193:1200 arg1 phosphorylation 1202:1216 elevated phosphorylation 1193:1216 elevated phosphorylation 1193:1216 In addition, elevated O-GlcNAcylation resulted in hnRNP A1 seclusion in the nucleus, whereas elevated phosphorylation resulted in its accumulation in the cytosol. 27913144 11 39 theme hnRNP 1545:1549 arg1 A1 1551:1552 hnRNP A1 1545:1552 hnRNP A1 1545:1552 There is a need for further study, to elucidate the role of O-GlcNAcylation in the regulation of the specific activities of hnRNP A1 in transcription and translation. 27913144 1 40 theme nuclear 109:115 arg1 protein 177:183 a major pre-mRNA binding protein 152:183 a major pre-mRNA binding protein involved in transcription and translation 152:225 The heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is a major pre-mRNA binding protein involved in transcription and translation. 27913144 1 40 theme nuclear 109:115 arg1 A1 135:136 The heterogeneous nuclear ribonucleoprotein A1 91:136 The heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) 91:147 The heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is a major pre-mRNA binding protein involved in transcription and translation. 27913144 1 40 theme nuclear 109:115 arg1 A1 145:146 hnRNP A1 139:146 hnRNP A1 139:146 The heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is a major pre-mRNA binding protein involved in transcription and translation. 27913144 9 41 theme A1 1156:1157 arg1 seclusion 1159:1167 hnRNP A1 seclusion 1150:1167 hnRNP A1 seclusion in the nucleus 1150:1182 In addition, elevated O-GlcNAcylation resulted in hnRNP A1 seclusion in the nucleus, whereas elevated phosphorylation resulted in its accumulation in the cytosol. 27913144 0 42 theme hnRNP 33:37 arg1 translocation 42:54 hnRNP A1 translocation 33:54 hnRNP A1 translocation 33:54 The effect of O-GlcNAcylation on hnRNP A1 translocation and interaction with transportin1. 27913144 9 43 theme elevated 1113:1120 arg1 O-GlcNAcylation 1122:1136 elevated O-GlcNAcylation 1113:1136 elevated O-GlcNAcylation 1113:1136 In addition, elevated O-GlcNAcylation resulted in hnRNP A1 seclusion in the nucleus, whereas elevated phosphorylation resulted in its accumulation in the cytosol. 27913144 11 44 theme specific 1522:1529 arg1 activities 1531:1540 the specific activities 1518:1540 the specific activities of hnRNP A1 in transcription and translation 1518:1585 There is a need for further study, to elucidate the role of O-GlcNAcylation in the regulation of the specific activities of hnRNP A1 in transcription and translation. 27913144 11 45 from role 1473:1476 arg1 regulation 1504:1513 the regulation 1500:1513 the regulation of the specific activities of hnRNP A1 in transcription and translation 1500:1585 There is a need for further study, to elucidate the role of O-GlcNAcylation in the regulation of the specific activities of hnRNP A1 in transcription and translation. 27913144 10 46 theme hnRNP 1338:1342 arg1 translocation 1347:1359 hnRNP A1 translocation 1338:1359 hnRNP A1 translocation 1338:1359 These findings suggest that a new player, i.e., O-GlcNAcylation, regulates hnRNP A1 translocation and interaction with Trn1, possibly affecting its function. 27913144 3 47 theme translational 458:470 arg1 roles 472:476 its transcriptional and translational roles 434:476 its transcriptional and translational roles 434:476 Translocation is important for hnRNP A1 to accomplish its transcriptional and translational roles. 27913144 3 48 theme transcriptional 438:452 arg1 roles 472:476 its transcriptional and translational roles 434:476 its transcriptional and translational roles 434:476 Translocation is important for hnRNP A1 to accomplish its transcriptional and translational roles. 27913144 9 49 from seclusion 1159:1167 arg1 nucleus 1176:1182 the nucleus 1172:1182 the nucleus 1172:1182 In addition, elevated O-GlcNAcylation resulted in hnRNP A1 seclusion in the nucleus, whereas elevated phosphorylation resulted in its accumulation in the cytosol. 27913144 10 50 with translocation 1347:1359 arg1 Trn1 1382:1385 Trn1 1382:1385 Trn1 1382:1385 These findings suggest that a new player, i.e., O-GlcNAcylation, regulates hnRNP A1 translocation and interaction with Trn1, possibly affecting its function. 27913144 1 51 theme ribonucleoprotein 117:133 arg1 protein 177:183 a major pre-mRNA binding protein 152:183 a major pre-mRNA binding protein involved in transcription and translation 152:225 The heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is a major pre-mRNA binding protein involved in transcription and translation. 27913144 1 51 theme ribonucleoprotein 117:133 arg1 A1 135:136 The heterogeneous nuclear ribonucleoprotein A1 91:136 The heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) 91:147 The heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is a major pre-mRNA binding protein involved in transcription and translation. 27913144 1 51 theme ribonucleoprotein 117:133 arg1 A1 145:146 hnRNP A1 139:146 hnRNP A1 139:146 The heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is a major pre-mRNA binding protein involved in transcription and translation. 27913144 3 52 theme hnRNP 411:415 arg1 A1 417:418 hnRNP A1 411:418 hnRNP A1 411:418 Translocation is important for hnRNP A1 to accomplish its transcriptional and translational roles. 27913144 6 53 theme only 746:749 arg1 modification 751:762 the only modification 742:762 the only modification that hnRNP A1 undergoes 742:786 In this study, we found that phosphorylation is not the only modification that hnRNP A1 undergoes, but also O-linked N-acetylglucosaminylation (O-GlcNAcylation) could occur. 27913144 6 53 theme only 746:749 arg1 phosphorylation 719:733 phosphorylation 719:733 phosphorylation 719:733 In this study, we found that phosphorylation is not the only modification that hnRNP A1 undergoes, but also O-linked N-acetylglucosaminylation (O-GlcNAcylation) could occur. 27913144 7 54 theme hnRNP 932:936 arg1 A1 938:939 hnRNP A1 932:939 hnRNP A1 932:939 Several putative novel O-GlcNAcylation and phosphorylation sites in hnRNP A1 were mapped. 27913144 5 55 from domain 656:661 arg1 phosphorylation 598:612 phosphorylation 598:612 phosphorylation of serine residues at hnRNP A1 C-terminal domain 598:661 Moreover, phosphorylation of serine residues at hnRNP A1 C-terminal domain affects its translocation. 27913144 11 56 theme A1 1551:1552 arg1 activities 1531:1540 the specific activities 1518:1540 the specific activities of hnRNP A1 in transcription and translation 1518:1585 There is a need for further study, to elucidate the role of O-GlcNAcylation in the regulation of the specific activities of hnRNP A1 in transcription and translation. 27913144 8 57 theme A1 1003:1004 arg1 interaction 1006:1016 hnRNP A1 interaction 997:1016 hnRNP A1 interaction with Trn1 997:1026 Whereas enhanced O-GlcNAcylation increased hnRNP A1 interaction with Trn1, enhanced phosphorylation reduced the interaction between the proteins. 27913144 2 58 theme hnRNP 260:264 arg1 A1 266:267 hnRNP A1 260:267 hnRNP A1 260:267 Although predominantly nuclear, hnRNP A1 shuttles rapidly between the nucleus and the cytosol, delivering its anchored pre-mRNA for further processing. 27913144 0 59 with translocation 42:54 arg1 transportin1 77:88 transportin1 77:88 transportin1 77:88 The effect of O-GlcNAcylation on hnRNP A1 translocation and interaction with transportin1. 27913144 1 60 theme hnRNP 139:143 arg1 A1 135:136 The heterogeneous nuclear ribonucleoprotein A1 91:136 The heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) 91:147 The heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is a major pre-mRNA binding protein involved in transcription and translation. 27913144 1 60 theme hnRNP 139:143 arg1 A1 145:146 hnRNP A1 139:146 hnRNP A1 139:146 The heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is a major pre-mRNA binding protein involved in transcription and translation. 27913144 11 61 theme activities 1531:1540 arg1 regulation 1504:1513 the regulation 1500:1513 the regulation of the specific activities of hnRNP A1 in transcription and translation 1500:1585 There is a need for further study, to elucidate the role of O-GlcNAcylation in the regulation of the specific activities of hnRNP A1 in transcription and translation. 27913144 8 62 theme enhanced 962:969 arg1 O-GlcNAcylation 971:985 enhanced O-GlcNAcylation 962:985 enhanced O-GlcNAcylation 962:985 Whereas enhanced O-GlcNAcylation increased hnRNP A1 interaction with Trn1, enhanced phosphorylation reduced the interaction between the proteins. 27913144 9 63 from accumulation 1234:1245 arg1 cytosol 1254:1260 the cytosol 1250:1260 the cytosol 1250:1260 In addition, elevated O-GlcNAcylation resulted in hnRNP A1 seclusion in the nucleus, whereas elevated phosphorylation resulted in its accumulation in the cytosol. 27913144 4 64 theme translocation 502:514 arg1 protein 516:522 a translocation protein 500:522 a translocation protein 500:522 Transportin1 (Trn1), a translocation protein, facilitates the translocation of hnRNP A1 back to the nucleus. 27913144 4 64 theme translocation 502:514 arg1 Transportin1 479:490 Transportin1 479:490 Transportin1 (Trn1) 479:497 Transportin1 (Trn1), a translocation protein, facilitates the translocation of hnRNP A1 back to the nucleus. 27913144 8 65 theme hnRNP 997:1001 arg1 A1 1003:1004 hnRNP A1 997:1004 hnRNP A1 interaction with Trn1 997:1026 Whereas enhanced O-GlcNAcylation increased hnRNP A1 interaction with Trn1, enhanced phosphorylation reduced the interaction between the proteins. 27913144 2 66 theme further 360:366 arg1 processing 368:377 further processing 360:377 further processing 360:377 Although predominantly nuclear, hnRNP A1 shuttles rapidly between the nucleus and the cytosol, delivering its anchored pre-mRNA for further processing. 27558639 6 0 theme Cys 832:834 arg1 modifications 836:848 Such Cys modifications 827:848 Such Cys modifications 827:848 Such Cys modifications have been detected and identified in mouse and rat samples. 27558639 1 1 theme well-known 164:173 arg1 modification 218:229 a well-known and widely investigated post-translational modification 162:229 a well-known and widely investigated post-translational modification 162:229 Intracellular GlcNAcylation of Ser and Thr residues is a well-known and widely investigated post-translational modification. 27558639 1 1 theme well-known 164:173 arg1 GlcNAcylation 121:133 Intracellular GlcNAcylation 107:133 Intracellular GlcNAcylation of Ser and Thr residues 107:157 Intracellular GlcNAcylation of Ser and Thr residues is a well-known and widely investigated post-translational modification. 27558639 5 2 theme responsible 738:748 arg1 O-GlcNAcase 714:724 O-GlcNAcase 714:724 O-GlcNAcase 714:724 We also report that O-GlcNAcase, the enzyme responsible for removal of O-GlcNAcylation does not appear to remove the S-linked sugar. 27558639 5 2 theme responsible 738:748 arg1 enzyme 731:736 the enzyme 727:736 the enzyme responsible for removal of O-GlcNAcylation 727:779 We also report that O-GlcNAcase, the enzyme responsible for removal of O-GlcNAcylation does not appear to remove the S-linked sugar. 27558639 8 3 theme Host 1066:1069 arg1 Factor 1076:1081 human Host Cell Factor 1 1060:1083 human Host Cell Factor 1 isolated from HEK-cells 1060:1107 We have also identified S-GlcNAcylation from human Host Cell Factor 1 isolated from HEK-cells. 27558639 3 4 theme glycosylating 427:439 arg1 proteins 463:470 glycosylating cytosolic and nuclear proteins 427:470 glycosylating cytosolic and nuclear proteins with a single GlcNAc residue on Ser and Thr side-chains 427:526 O-GlcNAc transferase is the enzyme responsible for glycosylating cytosolic and nuclear proteins with a single GlcNAc residue on Ser and Thr side-chains. 27558639 4 5 dep S-GlcNAcylation 593:607 arg1 i.e. 610:613 i.e. 610:613 i.e. 610:613 Here we report that the same enzyme may also be responsible for S-GlcNAcylation, i.e. for linking the GlcNAc unit to the peptide by modifying a cysteine side-chain. 27558639 8 6 theme human 1060:1064 arg1 Factor 1076:1081 human Host Cell Factor 1 1060:1083 human Host Cell Factor 1 isolated from HEK-cells 1060:1107 We have also identified S-GlcNAcylation from human Host Cell Factor 1 isolated from HEK-cells. 27558639 0 7 link S-linked 9:16 arg1 N-acetylglucosamine 18:36 Cysteine S-linked N-acetylglucosamine 0:36 Cysteine S-linked N-acetylglucosamine (S-GlcNAcylation) 0:54 Cysteine S-linked N-acetylglucosamine (S-GlcNAcylation), A New Post-translational Modification in Mammals. 27558639 0 7 link S-linked 9:16 arg1 Modification 82:93 A New Post-translational Modification 57:93 A New Post-translational Modification in Mammals 57:104 Cysteine S-linked N-acetylglucosamine (S-GlcNAcylation), A New Post-translational Modification in Mammals. 27558639 0 7 link S-linked 9:16 arg1 S-GlcNAcylation 39:53 S-GlcNAcylation 39:53 S-GlcNAcylation 39:53 Cysteine S-linked N-acetylglucosamine (S-GlcNAcylation), A New Post-translational Modification in Mammals. 27558639 2 8 theme cell 314:317 arg1 signaling 319:327 cell signaling 314:327 cell signaling 314:327 This post-translational modification has been shown to play a significant role in cell signaling and in many regulatory processes within cells. 27558639 3 9 theme O-GlcNAc 376:383 arg1 transferase 385:395 O-GlcNAc transferase 376:395 O-GlcNAc transferase 376:395 O-GlcNAc transferase is the enzyme responsible for glycosylating cytosolic and nuclear proteins with a single GlcNAc residue on Ser and Thr side-chains. 27558639 3 9 theme O-GlcNAc 376:383 arg1 enzyme 404:409 the enzyme 400:409 the enzyme responsible for glycosylating cytosolic and nuclear proteins with a single GlcNAc residue on Ser and Thr side-chains 400:526 O-GlcNAc transferase is the enzyme responsible for glycosylating cytosolic and nuclear proteins with a single GlcNAc residue on Ser and Thr side-chains. 27558639 3 10 gly glycosylating 427:439 arg0 proteins 463:470 glycosylating cytosolic and nuclear proteins 427:470 glycosylating cytosolic and nuclear proteins with a single GlcNAc residue on Ser and Thr side-chains 427:526 O-GlcNAc transferase is the enzyme responsible for glycosylating cytosolic and nuclear proteins with a single GlcNAc residue on Ser and Thr side-chains. 27558639 7 11 theme sites 970:974 arg1 occurrence 940:949 the occurrence 936:949 the occurrence of 14 modification sites assigned to 11 proteins 936:998 This work has established the occurrence of 14 modification sites assigned to 11 proteins unambiguously. 27558639 3 12 theme single 479:484 arg1 residue 493:499 a single GlcNAc residue 477:499 a single GlcNAc residue on Ser and Thr side-chains 477:526 O-GlcNAc transferase is the enzyme responsible for glycosylating cytosolic and nuclear proteins with a single GlcNAc residue on Ser and Thr side-chains. 27558639 6 13 theme rat 897:899 arg1 samples 901:907 mouse and rat samples 887:907 mouse and rat samples 887:907 Such Cys modifications have been detected and identified in mouse and rat samples. 27558639 8 14 theme Cell 1071:1074 arg1 Factor 1076:1081 human Host Cell Factor 1 1060:1083 human Host Cell Factor 1 isolated from HEK-cells 1060:1107 We have also identified S-GlcNAcylation from human Host Cell Factor 1 isolated from HEK-cells. 27558639 9 15 theme S-linked 1230:1237 arg1 GlcNAc 1239:1244 S-linked GlcNAc 1230:1244 S-linked GlcNAc 1230:1244 Although these site assignments are primarily based on electron-transfer dissociation mass spectra, we also report that S-linked GlcNAc is more stable under collisional activation than O-linked GlcNAc derivatives. 27558639 1 16 dep Ser 138:140 arg1 residues 150:157 residues 150:157 residues 150:157 Intracellular GlcNAcylation of Ser and Thr residues is a well-known and widely investigated post-translational modification. 27558639 3 17 theme GlcNAc 486:491 arg1 residue 493:499 a single GlcNAc residue 477:499 a single GlcNAc residue on Ser and Thr side-chains 477:526 O-GlcNAc transferase is the enzyme responsible for glycosylating cytosolic and nuclear proteins with a single GlcNAc residue on Ser and Thr side-chains. 27558639 0 18 theme S-linked 9:16 arg1 N-acetylglucosamine 18:36 Cysteine S-linked N-acetylglucosamine 0:36 Cysteine S-linked N-acetylglucosamine (S-GlcNAcylation) 0:54 Cysteine S-linked N-acetylglucosamine (S-GlcNAcylation), A New Post-translational Modification in Mammals. 27558639 0 18 theme S-linked 9:16 arg1 Modification 82:93 A New Post-translational Modification 57:93 A New Post-translational Modification in Mammals 57:104 Cysteine S-linked N-acetylglucosamine (S-GlcNAcylation), A New Post-translational Modification in Mammals. 27558639 0 18 theme S-linked 9:16 arg1 S-GlcNAcylation 39:53 S-GlcNAcylation 39:53 S-GlcNAcylation 39:53 Cysteine S-linked N-acetylglucosamine (S-GlcNAcylation), A New Post-translational Modification in Mammals. 27558639 5 19 theme O-GlcNAcylation 765:779 arg1 removal 754:760 removal 754:760 removal of O-GlcNAcylation 754:779 We also report that O-GlcNAcase, the enzyme responsible for removal of O-GlcNAcylation does not appear to remove the S-linked sugar. 27558639 2 20 theme regulatory 341:350 arg1 processes 352:360 many regulatory processes 336:360 many regulatory processes within cells 336:373 This post-translational modification has been shown to play a significant role in cell signaling and in many regulatory processes within cells. 27558639 1 21 theme investigated 186:197 arg1 modification 218:229 a well-known and widely investigated post-translational modification 162:229 a well-known and widely investigated post-translational modification 162:229 Intracellular GlcNAcylation of Ser and Thr residues is a well-known and widely investigated post-translational modification. 27558639 1 21 theme investigated 186:197 arg1 GlcNAcylation 121:133 Intracellular GlcNAcylation 107:133 Intracellular GlcNAcylation of Ser and Thr residues 107:157 Intracellular GlcNAcylation of Ser and Thr residues is a well-known and widely investigated post-translational modification. 27558639 0 22 theme Cysteine 0:7 arg1 N-acetylglucosamine 18:36 Cysteine S-linked N-acetylglucosamine 0:36 Cysteine S-linked N-acetylglucosamine (S-GlcNAcylation) 0:54 Cysteine S-linked N-acetylglucosamine (S-GlcNAcylation), A New Post-translational Modification in Mammals. 27558639 0 22 theme Cysteine 0:7 arg1 Modification 82:93 A New Post-translational Modification 57:93 A New Post-translational Modification in Mammals 57:104 Cysteine S-linked N-acetylglucosamine (S-GlcNAcylation), A New Post-translational Modification in Mammals. 27558639 0 22 theme Cysteine 0:7 arg1 S-GlcNAcylation 39:53 S-GlcNAcylation 39:53 S-GlcNAcylation 39:53 Cysteine S-linked N-acetylglucosamine (S-GlcNAcylation), A New Post-translational Modification in Mammals. 27558639 2 23 theme many 336:339 arg1 processes 352:360 many regulatory processes 336:360 many regulatory processes within cells 336:373 This post-translational modification has been shown to play a significant role in cell signaling and in many regulatory processes within cells. 27558639 1 24 theme post-translational 199:216 arg1 modification 218:229 a well-known and widely investigated post-translational modification 162:229 a well-known and widely investigated post-translational modification 162:229 Intracellular GlcNAcylation of Ser and Thr residues is a well-known and widely investigated post-translational modification. 27558639 1 24 theme post-translational 199:216 arg1 GlcNAcylation 121:133 Intracellular GlcNAcylation 107:133 Intracellular GlcNAcylation of Ser and Thr residues 107:157 Intracellular GlcNAcylation of Ser and Thr residues is a well-known and widely investigated post-translational modification. 27558639 7 25 theme modification 957:968 arg1 sites 970:974 14 modification sites 954:974 14 modification sites assigned to 11 proteins 954:998 This work has established the occurrence of 14 modification sites assigned to 11 proteins unambiguously. 27558639 1 26 theme Intracellular 107:119 arg1 modification 218:229 a well-known and widely investigated post-translational modification 162:229 a well-known and widely investigated post-translational modification 162:229 Intracellular GlcNAcylation of Ser and Thr residues is a well-known and widely investigated post-translational modification. 27558639 1 26 theme Intracellular 107:119 arg1 GlcNAcylation 121:133 Intracellular GlcNAcylation 107:133 Intracellular GlcNAcylation of Ser and Thr residues 107:157 Intracellular GlcNAcylation of Ser and Thr residues is a well-known and widely investigated post-translational modification. 27558639 9 27 theme site 1125:1128 arg1 assignments 1130:1140 these site assignments 1119:1140 these site assignments 1119:1140 Although these site assignments are primarily based on electron-transfer dissociation mass spectra, we also report that S-linked GlcNAc is more stable under collisional activation than O-linked GlcNAc derivatives. 27558639 3 28 theme responsible 411:421 arg1 transferase 385:395 O-GlcNAc transferase 376:395 O-GlcNAc transferase 376:395 O-GlcNAc transferase is the enzyme responsible for glycosylating cytosolic and nuclear proteins with a single GlcNAc residue on Ser and Thr side-chains. 27558639 3 28 theme responsible 411:421 arg1 enzyme 404:409 the enzyme 400:409 the enzyme responsible for glycosylating cytosolic and nuclear proteins with a single GlcNAc residue on Ser and Thr side-chains 400:526 O-GlcNAc transferase is the enzyme responsible for glycosylating cytosolic and nuclear proteins with a single GlcNAc residue on Ser and Thr side-chains. 27558639 6 29 theme mouse 887:891 arg1 samples 901:907 mouse and rat samples 887:907 mouse and rat samples 887:907 Such Cys modifications have been detected and identified in mouse and rat samples. 27558639 3 30 theme nuclear 455:461 arg1 proteins 463:470 glycosylating cytosolic and nuclear proteins 427:470 glycosylating cytosolic and nuclear proteins with a single GlcNAc residue on Ser and Thr side-chains 427:526 O-GlcNAc transferase is the enzyme responsible for glycosylating cytosolic and nuclear proteins with a single GlcNAc residue on Ser and Thr side-chains. 27558639 0 31 from Modification 82:93 arg1 Mammals 98:104 Mammals 98:104 Mammals 98:104 Cysteine S-linked N-acetylglucosamine (S-GlcNAcylation), A New Post-translational Modification in Mammals. 27558639 9 32 theme electron-transfer 1165:1181 arg1 spectra 1201:1207 electron-transfer dissociation mass spectra 1165:1207 electron-transfer dissociation mass spectra 1165:1207 Although these site assignments are primarily based on electron-transfer dissociation mass spectra, we also report that S-linked GlcNAc is more stable under collisional activation than O-linked GlcNAc derivatives. 27558639 4 33 theme cysteine 673:680 arg1 side-chain 682:691 a cysteine side-chain 671:691 a cysteine side-chain 671:691 Here we report that the same enzyme may also be responsible for S-GlcNAcylation, i.e. for linking the GlcNAc unit to the peptide by modifying a cysteine side-chain. 27558639 9 34 theme collisional 1267:1277 arg1 activation 1279:1288 collisional activation 1267:1288 collisional activation than O-linked GlcNAc derivatives 1267:1321 Although these site assignments are primarily based on electron-transfer dissociation mass spectra, we also report that S-linked GlcNAc is more stable under collisional activation than O-linked GlcNAc derivatives. 27558639 5 35 link S-linked 811:818 arg1 sugar 820:824 the S-linked sugar 807:824 the S-linked sugar 807:824 We also report that O-GlcNAcase, the enzyme responsible for removal of O-GlcNAcylation does not appear to remove the S-linked sugar. 27558639 3 36 from residue 493:499 arg1 Thr 512:514 Thr 512:514 Thr 512:514 O-GlcNAc transferase is the enzyme responsible for glycosylating cytosolic and nuclear proteins with a single GlcNAc residue on Ser and Thr side-chains. 27558639 3 36 from residue 493:499 arg1 Ser 504:506 Ser 504:506 Ser 504:506 O-GlcNAc transferase is the enzyme responsible for glycosylating cytosolic and nuclear proteins with a single GlcNAc residue on Ser and Thr side-chains. 27558639 8 37 attach isolated 1085:1092 arg2 Factor 1076:1081 human Host Cell Factor 1 1060:1083 human Host Cell Factor 1 isolated from HEK-cells 1060:1107 We have also identified S-GlcNAcylation from human Host Cell Factor 1 isolated from HEK-cells. 27558639 8 37 attach isolated 1085:1092 arg1 HEK-cells 1099:1107 HEK-cells 1099:1107 HEK-cells 1099:1107 We have also identified S-GlcNAcylation from human Host Cell Factor 1 isolated from HEK-cells. 27558639 3 38 theme cytosolic 441:449 arg1 proteins 463:470 glycosylating cytosolic and nuclear proteins 427:470 glycosylating cytosolic and nuclear proteins with a single GlcNAc residue on Ser and Thr side-chains 427:526 O-GlcNAc transferase is the enzyme responsible for glycosylating cytosolic and nuclear proteins with a single GlcNAc residue on Ser and Thr side-chains. 27558639 4 39 theme same 553:556 arg1 responsible 577:587 responsible 577:587 responsible 577:587 Here we report that the same enzyme may also be responsible for S-GlcNAcylation, i.e. for linking the GlcNAc unit to the peptide by modifying a cysteine side-chain. 27558639 4 39 theme same 553:556 arg1 enzyme 558:563 the same enzyme 549:563 the same enzyme 549:563 Here we report that the same enzyme may also be responsible for S-GlcNAcylation, i.e. for linking the GlcNAc unit to the peptide by modifying a cysteine side-chain. 27558639 5 40 theme S-linked 811:818 arg1 sugar 820:824 the S-linked sugar 807:824 the S-linked sugar 807:824 We also report that O-GlcNAcase, the enzyme responsible for removal of O-GlcNAcylation does not appear to remove the S-linked sugar. 27558639 2 41 theme post-translational 237:254 arg1 modification 256:267 This post-translational modification 232:267 This post-translational modification 232:267 This post-translational modification has been shown to play a significant role in cell signaling and in many regulatory processes within cells. 27558639 1 42 theme Ser 138:140 arg1 modification 218:229 a well-known and widely investigated post-translational modification 162:229 a well-known and widely investigated post-translational modification 162:229 Intracellular GlcNAcylation of Ser and Thr residues is a well-known and widely investigated post-translational modification. 27558639 1 42 theme Ser 138:140 arg1 GlcNAcylation 121:133 Intracellular GlcNAcylation 107:133 Intracellular GlcNAcylation of Ser and Thr residues 107:157 Intracellular GlcNAcylation of Ser and Thr residues is a well-known and widely investigated post-translational modification. 27558639 9 43 theme O-linked 1295:1302 arg1 derivatives 1311:1321 O-linked GlcNAc derivatives 1295:1321 O-linked GlcNAc derivatives 1295:1321 Although these site assignments are primarily based on electron-transfer dissociation mass spectra, we also report that S-linked GlcNAc is more stable under collisional activation than O-linked GlcNAc derivatives. 27558639 2 44 theme significant 294:304 arg1 role 306:309 a significant role 292:309 a significant role 292:309 This post-translational modification has been shown to play a significant role in cell signaling and in many regulatory processes within cells. 27558639 6 45 theme Such 827:830 arg1 modifications 836:848 Such Cys modifications 827:848 Such Cys modifications 827:848 Such Cys modifications have been detected and identified in mouse and rat samples. 27558639 4 46 theme GlcNAc 631:636 arg1 unit 638:641 the GlcNAc unit 627:641 the GlcNAc unit to the peptide 627:656 Here we report that the same enzyme may also be responsible for S-GlcNAcylation, i.e. for linking the GlcNAc unit to the peptide by modifying a cysteine side-chain. 27558639 3 47 with proteins 463:470 arg1 residue 493:499 a single GlcNAc residue 477:499 a single GlcNAc residue on Ser and Thr side-chains 477:526 O-GlcNAc transferase is the enzyme responsible for glycosylating cytosolic and nuclear proteins with a single GlcNAc residue on Ser and Thr side-chains. 27558639 9 48 theme GlcNAc 1304:1309 arg1 derivatives 1311:1321 O-linked GlcNAc derivatives 1295:1321 O-linked GlcNAc derivatives 1295:1321 Although these site assignments are primarily based on electron-transfer dissociation mass spectra, we also report that S-linked GlcNAc is more stable under collisional activation than O-linked GlcNAc derivatives. 27558639 9 49 theme dissociation 1183:1194 arg1 spectra 1201:1207 electron-transfer dissociation mass spectra 1165:1207 electron-transfer dissociation mass spectra 1165:1207 Although these site assignments are primarily based on electron-transfer dissociation mass spectra, we also report that S-linked GlcNAc is more stable under collisional activation than O-linked GlcNAc derivatives. 27558639 1 50 theme Thr 146:148 arg1 modification 218:229 a well-known and widely investigated post-translational modification 162:229 a well-known and widely investigated post-translational modification 162:229 Intracellular GlcNAcylation of Ser and Thr residues is a well-known and widely investigated post-translational modification. 27558639 1 50 theme Thr 146:148 arg1 GlcNAcylation 121:133 Intracellular GlcNAcylation 107:133 Intracellular GlcNAcylation of Ser and Thr residues 107:157 Intracellular GlcNAcylation of Ser and Thr residues is a well-known and widely investigated post-translational modification. 27558639 0 51 theme Post-translational 63:80 arg1 Modification 82:93 A New Post-translational Modification 57:93 A New Post-translational Modification in Mammals 57:104 Cysteine S-linked N-acetylglucosamine (S-GlcNAcylation), A New Post-translational Modification in Mammals. 27558639 0 51 theme Post-translational 63:80 arg1 N-acetylglucosamine 18:36 Cysteine S-linked N-acetylglucosamine 0:36 Cysteine S-linked N-acetylglucosamine (S-GlcNAcylation) 0:54 Cysteine S-linked N-acetylglucosamine (S-GlcNAcylation), A New Post-translational Modification in Mammals. 27558639 3 52 dep Ser 504:506 arg1 side-chains 516:526 side-chains 516:526 side-chains 516:526 O-GlcNAc transferase is the enzyme responsible for glycosylating cytosolic and nuclear proteins with a single GlcNAc residue on Ser and Thr side-chains. 27558639 9 53 theme mass 1196:1199 arg1 spectra 1201:1207 electron-transfer dissociation mass spectra 1165:1207 electron-transfer dissociation mass spectra 1165:1207 Although these site assignments are primarily based on electron-transfer dissociation mass spectra, we also report that S-linked GlcNAc is more stable under collisional activation than O-linked GlcNAc derivatives. 27558639 9 54 link O-linked 1295:1302 arg1 derivatives 1311:1321 O-linked GlcNAc derivatives 1295:1321 O-linked GlcNAc derivatives 1295:1321 Although these site assignments are primarily based on electron-transfer dissociation mass spectra, we also report that S-linked GlcNAc is more stable under collisional activation than O-linked GlcNAc derivatives. 27558639 9 55 link S-linked 1230:1237 arg1 GlcNAc 1239:1244 S-linked GlcNAc 1230:1244 S-linked GlcNAc 1230:1244 Although these site assignments are primarily based on electron-transfer dissociation mass spectra, we also report that S-linked GlcNAc is more stable under collisional activation than O-linked GlcNAc derivatives. 27558639 0 56 theme New 59:61 arg1 Modification 82:93 A New Post-translational Modification 57:93 A New Post-translational Modification in Mammals 57:104 Cysteine S-linked N-acetylglucosamine (S-GlcNAcylation), A New Post-translational Modification in Mammals. 27558639 0 56 theme New 59:61 arg1 N-acetylglucosamine 18:36 Cysteine S-linked N-acetylglucosamine 0:36 Cysteine S-linked N-acetylglucosamine (S-GlcNAcylation) 0:54 Cysteine S-linked N-acetylglucosamine (S-GlcNAcylation), A New Post-translational Modification in Mammals. 26644575 4 0 theme cadherins 920:928 arg1 family 910:915 the large family 900:915 the large family of cadherins and protocadherins 900:947 We previously developed a sensitive lectin enrichment and mass spectrometry workflow for identification of the human O-linked mannose (O-Man) glycoproteome and used this to identify a pleothora of O-Man glycoproteins in human cell lines including the large family of cadherins and protocadherins. 26644575 8 1 theme nucleocytoplasmic 1663:1679 arg1 glycosylations 1687:1700 the nucleocytoplasmic O-Man glycosylations 1659:1700 the nucleocytoplasmic O-Man glycosylations 1659:1700 The discovery opens for exploration of the enzymatic machinery that is predicted to regulate the nucleocytoplasmic O-Man glycosylations. 26644575 4 2 theme protocadherins 934:947 arg1 family 910:915 the large family 900:915 the large family of cadherins and protocadherins 900:947 We previously developed a sensitive lectin enrichment and mass spectrometry workflow for identification of the human O-linked mannose (O-Man) glycoproteome and used this to identify a pleothora of O-Man glycoproteins in human cell lines including the large family of cadherins and protocadherins. 26644575 9 3 contain have 1775:1778 arg2 applications 1785:1796 wide applications 1780:1796 wide applications 1780:1796 It is likely that manipulation of this type of O-Man glycosylation will have wide applications for yeast bioprocessing. 26644575 9 3 contain have 1775:1778 arg1 manipulation 1721:1732 manipulation 1721:1732 manipulation of this type of O-Man glycosylation 1721:1768 It is likely that manipulation of this type of O-Man glycosylation will have wide applications for yeast bioprocessing. 26644575 7 4 theme different 1483:1491 arg1 types 1493:1497 the two different types 1475:1497 the two different types of O-glycosylations 1475:1517 However, the type of yeast O-Man nucleocytoplasmic proteins and the localization of identified O-Man residues mirror that of the O-GlcNAc glycoproteome found in other eukaryotic cells, indicating that the two different types of O-glycosylations serve the same important biological functions. 26644575 6 5 theme Such 1197:1200 arg1 glycoproteins 1208:1220 Such O-Man glycoproteins 1197:1220 Such O-Man glycoproteins 1197:1220 Such O-Man glycoproteins were not found in our analysis of human cell lines. 26644575 6 6 theme cell 1262:1265 arg1 lines 1267:1271 human cell lines 1256:1271 human cell lines 1256:1271 Such O-Man glycoproteins were not found in our analysis of human cell lines. 26644575 2 7 theme cellular 334:341 arg1 processes 343:351 cellular processes 334:351 cellular processes 334:351 O-GlcNAcylation modulates signaling and cellular processes in an intricate interplay with protein phosphorylation and serves as a key sensor of nutrients by linking the hexosamine biosynthetic pathway to cellular signaling. 26644575 9 8 theme type 1742:1745 arg1 manipulation 1721:1732 manipulation 1721:1732 manipulation of this type of O-Man glycosylation 1721:1768 It is likely that manipulation of this type of O-Man glycosylation will have wide applications for yeast bioprocessing. 26644575 4 9 theme lectin 689:694 arg1 enrichment 696:705 a sensitive lectin enrichment 677:705 a sensitive lectin enrichment 677:705 We previously developed a sensitive lectin enrichment and mass spectrometry workflow for identification of the human O-linked mannose (O-Man) glycoproteome and used this to identify a pleothora of O-Man glycoproteins in human cell lines including the large family of cadherins and protocadherins. 26644575 5 10 theme O-Man 1097:1101 arg1 glycosites 1103:1112 hitherto unknown O-Man glycosites 1080:1112 hitherto unknown O-Man glycosites 1080:1112 Here, we applied the workflow to yeast with the aim to characterize the yeast O-Man glycoproteome, and in doing so, we discovered hitherto unknown O-Man glycosites on nuclear, cytoplasmic, and mitochondrial proteins in S. cerevisiae and S. pombe. 26644575 9 11 theme O-Man 1750:1754 arg1 glycosylation 1756:1768 O-Man glycosylation 1750:1768 O-Man glycosylation 1750:1768 It is likely that manipulation of this type of O-Man glycosylation will have wide applications for yeast bioprocessing. 26644575 6 12 theme human 1256:1260 arg1 lines 1267:1271 human cell lines 1256:1271 human cell lines 1256:1271 Such O-Man glycoproteins were not found in our analysis of human cell lines. 26644575 6 13 gly glycoproteins 1208:1220 arg1 glycoproteins 1208:1220 Such O-Man glycoproteins 1197:1220 Such O-Man glycoproteins 1197:1220 Such O-Man glycoproteins were not found in our analysis of human cell lines. 26644575 4 14 theme mannose 779:785 arg1 glycoproteome 795:807 the human O-linked mannose (O-Man) glycoproteome 760:807 the human O-linked mannose (O-Man) glycoproteome 760:807 We previously developed a sensitive lectin enrichment and mass spectrometry workflow for identification of the human O-linked mannose (O-Man) glycoproteome and used this to identify a pleothora of O-Man glycoproteins in human cell lines including the large family of cadherins and protocadherins. 26644575 3 15 theme signaling 635:643 arg1 system 645:650 its similar phosphorylation signaling system 607:650 its similar phosphorylation signaling system 607:650 A longstanding conundrum has been how yeast survives without O-GlcNAcylation in light of its similar phosphorylation signaling system. 26644575 9 16 theme wide 1780:1783 arg1 applications 1785:1796 wide applications 1780:1796 wide applications 1780:1796 It is likely that manipulation of this type of O-Man glycosylation will have wide applications for yeast bioprocessing. 26644575 7 17 theme residues 1375:1382 arg1 localization 1342:1353 the localization 1338:1353 the localization of identified O-Man residues 1338:1382 However, the type of yeast O-Man nucleocytoplasmic proteins and the localization of identified O-Man residues mirror that of the O-GlcNAc glycoproteome found in other eukaryotic cells, indicating that the two different types of O-glycosylations serve the same important biological functions. 26644575 7 17 theme residues 1375:1382 arg1 type 1287:1290 the type 1283:1290 the type of yeast O-Man nucleocytoplasmic proteins 1283:1332 However, the type of yeast O-Man nucleocytoplasmic proteins and the localization of identified O-Man residues mirror that of the O-GlcNAc glycoproteome found in other eukaryotic cells, indicating that the two different types of O-glycosylations serve the same important biological functions. 26644575 4 18 theme O-Man 788:792 arg1 glycoproteome 795:807 the human O-linked mannose (O-Man) glycoproteome 760:807 the human O-linked mannose (O-Man) glycoproteome 760:807 We previously developed a sensitive lectin enrichment and mass spectrometry workflow for identification of the human O-linked mannose (O-Man) glycoproteome and used this to identify a pleothora of O-Man glycoproteins in human cell lines including the large family of cadherins and protocadherins. 26644575 7 19 theme identified 1358:1367 arg1 residues 1375:1382 identified O-Man residues 1358:1382 identified O-Man residues 1358:1382 However, the type of yeast O-Man nucleocytoplasmic proteins and the localization of identified O-Man residues mirror that of the O-GlcNAc glycoproteome found in other eukaryotic cells, indicating that the two different types of O-glycosylations serve the same important biological functions. 26644575 5 20 theme mitochondrial 1143:1155 arg1 proteins 1157:1164 nuclear, cytoplasmic, and mitochondrial proteins 1117:1164 nuclear, cytoplasmic, and mitochondrial proteins in S. cerevisiae and S. pombe 1117:1194 Here, we applied the workflow to yeast with the aim to characterize the yeast O-Man glycoproteome, and in doing so, we discovered hitherto unknown O-Man glycosites on nuclear, cytoplasmic, and mitochondrial proteins in S. cerevisiae and S. pombe. 26644575 4 21 theme human 764:768 arg1 glycoproteome 795:807 the human O-linked mannose (O-Man) glycoproteome 760:807 the human O-linked mannose (O-Man) glycoproteome 760:807 We previously developed a sensitive lectin enrichment and mass spectrometry workflow for identification of the human O-linked mannose (O-Man) glycoproteome and used this to identify a pleothora of O-Man glycoproteins in human cell lines including the large family of cadherins and protocadherins. 26644575 1 22 theme Dynamic 67:73 arg1 cycling 75:81 Dynamic cycling 67:81 Dynamic cycling of N-Acetylglucosamine (GlcNAc) on serine and threonine residues (O-GlcNAcylation) 67:164 Dynamic cycling of N-Acetylglucosamine (GlcNAc) on serine and threonine residues (O-GlcNAcylation) is an essential process in all eukaryotic cells except yeast, including Saccharomyces cerevisiae and Schizosaccharomyces pombe. 26644575 1 22 theme Dynamic 67:73 arg1 process 182:188 an essential process 169:188 an essential process in all eukaryotic cells except yeast, including Saccharomyces cerevisiae and Schizosaccharomyces pombe 169:291 Dynamic cycling of N-Acetylglucosamine (GlcNAc) on serine and threonine residues (O-GlcNAcylation) is an essential process in all eukaryotic cells except yeast, including Saccharomyces cerevisiae and Schizosaccharomyces pombe. 26644575 5 23 with workflow 971:978 arg1 aim 998:1000 the aim to characterize the yeast O-Man glycoproteome 994:1046 the aim to characterize the yeast O-Man glycoproteome 994:1046 Here, we applied the workflow to yeast with the aim to characterize the yeast O-Man glycoproteome, and in doing so, we discovered hitherto unknown O-Man glycosites on nuclear, cytoplasmic, and mitochondrial proteins in S. cerevisiae and S. pombe. 26644575 2 24 theme key 424:426 arg1 O-GlcNAcylation 294:308 O-GlcNAcylation 294:308 O-GlcNAcylation 294:308 O-GlcNAcylation modulates signaling and cellular processes in an intricate interplay with protein phosphorylation and serves as a key sensor of nutrients by linking the hexosamine biosynthetic pathway to cellular signaling. 26644575 2 24 theme key 424:426 arg1 sensor 428:433 a key sensor 422:433 a key sensor of nutrients 422:446 O-GlcNAcylation modulates signaling and cellular processes in an intricate interplay with protein phosphorylation and serves as a key sensor of nutrients by linking the hexosamine biosynthetic pathway to cellular signaling. 26644575 5 25 theme yeast 1022:1026 arg1 glycoproteome 1034:1046 the yeast O-Man glycoproteome 1018:1046 the yeast O-Man glycoproteome 1018:1046 Here, we applied the workflow to yeast with the aim to characterize the yeast O-Man glycoproteome, and in doing so, we discovered hitherto unknown O-Man glycosites on nuclear, cytoplasmic, and mitochondrial proteins in S. cerevisiae and S. pombe. 26644575 2 26 theme biosynthetic 474:485 arg1 pathway 487:493 the hexosamine biosynthetic pathway 459:493 the hexosamine biosynthetic pathway 459:493 O-GlcNAcylation modulates signaling and cellular processes in an intricate interplay with protein phosphorylation and serves as a key sensor of nutrients by linking the hexosamine biosynthetic pathway to cellular signaling. 26644575 4 27 theme glycoproteome 795:807 arg1 identification 742:755 identification 742:755 identification of the human O-linked mannose (O-Man) glycoproteome 742:807 We previously developed a sensitive lectin enrichment and mass spectrometry workflow for identification of the human O-linked mannose (O-Man) glycoproteome and used this to identify a pleothora of O-Man glycoproteins in human cell lines including the large family of cadherins and protocadherins. 26644575 7 28 theme eukaryotic 1441:1450 arg1 cells 1452:1456 other eukaryotic cells 1435:1456 other eukaryotic cells 1435:1456 However, the type of yeast O-Man nucleocytoplasmic proteins and the localization of identified O-Man residues mirror that of the O-GlcNAc glycoproteome found in other eukaryotic cells, indicating that the two different types of O-glycosylations serve the same important biological functions. 26644575 7 29 theme proteins 1325:1332 arg1 localization 1342:1353 the localization 1338:1353 the localization of identified O-Man residues 1338:1382 However, the type of yeast O-Man nucleocytoplasmic proteins and the localization of identified O-Man residues mirror that of the O-GlcNAc glycoproteome found in other eukaryotic cells, indicating that the two different types of O-glycosylations serve the same important biological functions. 26644575 7 29 theme proteins 1325:1332 arg1 type 1287:1290 the type 1283:1290 the type of yeast O-Man nucleocytoplasmic proteins 1283:1332 However, the type of yeast O-Man nucleocytoplasmic proteins and the localization of identified O-Man residues mirror that of the O-GlcNAc glycoproteome found in other eukaryotic cells, indicating that the two different types of O-glycosylations serve the same important biological functions. 26644575 4 30 theme human 873:877 arg1 family 910:915 the large family 900:915 the large family of cadherins and protocadherins 900:947 We previously developed a sensitive lectin enrichment and mass spectrometry workflow for identification of the human O-linked mannose (O-Man) glycoproteome and used this to identify a pleothora of O-Man glycoproteins in human cell lines including the large family of cadherins and protocadherins. 26644575 4 30 theme human 873:877 arg1 lines 884:888 human cell lines 873:888 human cell lines including the large family of cadherins and protocadherins 873:947 We previously developed a sensitive lectin enrichment and mass spectrometry workflow for identification of the human O-linked mannose (O-Man) glycoproteome and used this to identify a pleothora of O-Man glycoproteins in human cell lines including the large family of cadherins and protocadherins. 26644575 0 31 theme O-mannose 33:41 arg1 Discovery 0:8 Discovery 0:8 Discovery of a nucleocytoplasmic O-mannose 0:41 Discovery of a nucleocytoplasmic O-mannose glycoproteome in yeast. 26644575 2 32 with interplay 369:377 arg1 phosphorylation 392:406 protein phosphorylation 384:406 protein phosphorylation 384:406 O-GlcNAcylation modulates signaling and cellular processes in an intricate interplay with protein phosphorylation and serves as a key sensor of nutrients by linking the hexosamine biosynthetic pathway to cellular signaling. 26644575 7 33 theme O-Man 1301:1305 arg1 proteins 1325:1332 yeast O-Man nucleocytoplasmic proteins 1295:1332 yeast O-Man nucleocytoplasmic proteins 1295:1332 However, the type of yeast O-Man nucleocytoplasmic proteins and the localization of identified O-Man residues mirror that of the O-GlcNAc glycoproteome found in other eukaryotic cells, indicating that the two different types of O-glycosylations serve the same important biological functions. 26644575 3 34 theme longstanding 520:531 arg1 conundrum 533:541 A longstanding conundrum 518:541 A longstanding conundrum 518:541 A longstanding conundrum has been how yeast survives without O-GlcNAcylation in light of its similar phosphorylation signaling system. 26644575 5 35 from proteins 1157:1164 arg1 cerevisiae 1172:1181 S. cerevisiae 1169:1181 S. cerevisiae 1169:1181 Here, we applied the workflow to yeast with the aim to characterize the yeast O-Man glycoproteome, and in doing so, we discovered hitherto unknown O-Man glycosites on nuclear, cytoplasmic, and mitochondrial proteins in S. cerevisiae and S. pombe. 26644575 5 35 from proteins 1157:1164 arg1 pombe 1190:1194 S. pombe 1187:1194 S. pombe 1187:1194 Here, we applied the workflow to yeast with the aim to characterize the yeast O-Man glycoproteome, and in doing so, we discovered hitherto unknown O-Man glycosites on nuclear, cytoplasmic, and mitochondrial proteins in S. cerevisiae and S. pombe. 26644575 7 36 theme important 1534:1542 arg1 functions 1555:1563 the same important biological functions 1525:1563 the same important biological functions 1525:1563 However, the type of yeast O-Man nucleocytoplasmic proteins and the localization of identified O-Man residues mirror that of the O-GlcNAc glycoproteome found in other eukaryotic cells, indicating that the two different types of O-glycosylations serve the same important biological functions. 26644575 5 37 gly glycosites 1103:1112 arg2 glycosites 1103:1112 hitherto unknown O-Man glycosites 1080:1112 hitherto unknown O-Man glycosites 1080:1112 Here, we applied the workflow to yeast with the aim to characterize the yeast O-Man glycoproteome, and in doing so, we discovered hitherto unknown O-Man glycosites on nuclear, cytoplasmic, and mitochondrial proteins in S. cerevisiae and S. pombe. 26644575 8 38 theme machinery 1619:1627 arg1 exploration 1590:1600 exploration 1590:1600 exploration of the enzymatic machinery that is predicted to regulate the nucleocytoplasmic O-Man glycosylations 1590:1700 The discovery opens for exploration of the enzymatic machinery that is predicted to regulate the nucleocytoplasmic O-Man glycosylations. 26644575 4 39 theme glycoproteins 856:868 arg1 pleothora 837:845 a pleothora 835:845 a pleothora of O-Man glycoproteins in human cell lines including the large family of cadherins and protocadherins 835:947 We previously developed a sensitive lectin enrichment and mass spectrometry workflow for identification of the human O-linked mannose (O-Man) glycoproteome and used this to identify a pleothora of O-Man glycoproteins in human cell lines including the large family of cadherins and protocadherins. 26644575 7 40 theme O-glycosylations 1502:1517 arg1 types 1493:1497 the two different types 1475:1497 the two different types of O-glycosylations 1475:1517 However, the type of yeast O-Man nucleocytoplasmic proteins and the localization of identified O-Man residues mirror that of the O-GlcNAc glycoproteome found in other eukaryotic cells, indicating that the two different types of O-glycosylations serve the same important biological functions. 26644575 2 41 theme protein 384:390 arg1 phosphorylation 392:406 protein phosphorylation 384:406 protein phosphorylation 384:406 O-GlcNAcylation modulates signaling and cellular processes in an intricate interplay with protein phosphorylation and serves as a key sensor of nutrients by linking the hexosamine biosynthetic pathway to cellular signaling. 26644575 4 42 used used 813:816 arg2 We 653:654 We 653:654 We 653:654 We previously developed a sensitive lectin enrichment and mass spectrometry workflow for identification of the human O-linked mannose (O-Man) glycoproteome and used this to identify a pleothora of O-Man glycoproteins in human cell lines including the large family of cadherins and protocadherins. 26644575 6 43 theme O-Man 1202:1206 arg1 glycoproteins 1208:1220 Such O-Man glycoproteins 1197:1220 Such O-Man glycoproteins 1197:1220 Such O-Man glycoproteins were not found in our analysis of human cell lines. 26644575 8 44 theme O-Man 1681:1685 arg1 glycosylations 1687:1700 the nucleocytoplasmic O-Man glycosylations 1659:1700 the nucleocytoplasmic O-Man glycosylations 1659:1700 The discovery opens for exploration of the enzymatic machinery that is predicted to regulate the nucleocytoplasmic O-Man glycosylations. 26644575 4 45 gly glycoproteins 856:868 arg1 glycoproteins 856:868 O-Man glycoproteins 850:868 O-Man glycoproteins 850:868 We previously developed a sensitive lectin enrichment and mass spectrometry workflow for identification of the human O-linked mannose (O-Man) glycoproteome and used this to identify a pleothora of O-Man glycoproteins in human cell lines including the large family of cadherins and protocadherins. 26644575 4 46 link O-linked 770:777 arg1 glycoproteome 795:807 the human O-linked mannose (O-Man) glycoproteome 760:807 the human O-linked mannose (O-Man) glycoproteome 760:807 We previously developed a sensitive lectin enrichment and mass spectrometry workflow for identification of the human O-linked mannose (O-Man) glycoproteome and used this to identify a pleothora of O-Man glycoproteins in human cell lines including the large family of cadherins and protocadherins. 26644575 4 47 theme mass 711:714 arg1 spectrometry 716:727 mass spectrometry 711:727 mass spectrometry 711:727 We previously developed a sensitive lectin enrichment and mass spectrometry workflow for identification of the human O-linked mannose (O-Man) glycoproteome and used this to identify a pleothora of O-Man glycoproteins in human cell lines including the large family of cadherins and protocadherins. 26644575 6 48 theme lines 1267:1271 arg1 analysis 1244:1251 our analysis 1240:1251 our analysis of human cell lines 1240:1271 Such O-Man glycoproteins were not found in our analysis of human cell lines. 26644575 1 49 theme essential 172:180 arg1 cycling 75:81 Dynamic cycling 67:81 Dynamic cycling of N-Acetylglucosamine (GlcNAc) on serine and threonine residues (O-GlcNAcylation) 67:164 Dynamic cycling of N-Acetylglucosamine (GlcNAc) on serine and threonine residues (O-GlcNAcylation) is an essential process in all eukaryotic cells except yeast, including Saccharomyces cerevisiae and Schizosaccharomyces pombe. 26644575 1 49 theme essential 172:180 arg1 process 182:188 an essential process 169:188 an essential process in all eukaryotic cells except yeast, including Saccharomyces cerevisiae and Schizosaccharomyces pombe 169:291 Dynamic cycling of N-Acetylglucosamine (GlcNAc) on serine and threonine residues (O-GlcNAcylation) is an essential process in all eukaryotic cells except yeast, including Saccharomyces cerevisiae and Schizosaccharomyces pombe. 26644575 4 50 theme large 904:908 arg1 family 910:915 the large family 900:915 the large family of cadherins and protocadherins 900:947 We previously developed a sensitive lectin enrichment and mass spectrometry workflow for identification of the human O-linked mannose (O-Man) glycoproteome and used this to identify a pleothora of O-Man glycoproteins in human cell lines including the large family of cadherins and protocadherins. 26644575 7 51 theme other 1435:1439 arg1 cells 1452:1456 other eukaryotic cells 1435:1456 other eukaryotic cells 1435:1456 However, the type of yeast O-Man nucleocytoplasmic proteins and the localization of identified O-Man residues mirror that of the O-GlcNAc glycoproteome found in other eukaryotic cells, indicating that the two different types of O-glycosylations serve the same important biological functions. 26644575 4 52 theme workflow 729:736 arg1 enrichment 696:705 a sensitive lectin enrichment 677:705 a sensitive lectin enrichment 677:705 We previously developed a sensitive lectin enrichment and mass spectrometry workflow for identification of the human O-linked mannose (O-Man) glycoproteome and used this to identify a pleothora of O-Man glycoproteins in human cell lines including the large family of cadherins and protocadherins. 26644575 3 53 theme similar 611:617 arg1 system 645:650 its similar phosphorylation signaling system 607:650 its similar phosphorylation signaling system 607:650 A longstanding conundrum has been how yeast survives without O-GlcNAcylation in light of its similar phosphorylation signaling system. 26644575 4 54 theme sensitive 679:687 arg1 enrichment 696:705 a sensitive lectin enrichment 677:705 a sensitive lectin enrichment 677:705 We previously developed a sensitive lectin enrichment and mass spectrometry workflow for identification of the human O-linked mannose (O-Man) glycoproteome and used this to identify a pleothora of O-Man glycoproteins in human cell lines including the large family of cadherins and protocadherins. 26644575 3 55 theme system 645:650 arg1 light 598:602 light 598:602 light of its similar phosphorylation signaling system 598:650 A longstanding conundrum has been how yeast survives without O-GlcNAcylation in light of its similar phosphorylation signaling system. 26644575 1 56 theme eukaryotic 197:206 arg1 cerevisiae 252:261 Saccharomyces cerevisiae 238:261 Saccharomyces cerevisiae 238:261 Dynamic cycling of N-Acetylglucosamine (GlcNAc) on serine and threonine residues (O-GlcNAcylation) is an essential process in all eukaryotic cells except yeast, including Saccharomyces cerevisiae and Schizosaccharomyces pombe. 26644575 1 56 theme eukaryotic 197:206 arg1 pombe 287:291 Schizosaccharomyces pombe 267:291 Schizosaccharomyces pombe 267:291 Dynamic cycling of N-Acetylglucosamine (GlcNAc) on serine and threonine residues (O-GlcNAcylation) is an essential process in all eukaryotic cells except yeast, including Saccharomyces cerevisiae and Schizosaccharomyces pombe. 26644575 1 56 theme eukaryotic 197:206 arg1 cells 208:212 all eukaryotic cells 193:212 all eukaryotic cells 193:212 Dynamic cycling of N-Acetylglucosamine (GlcNAc) on serine and threonine residues (O-GlcNAcylation) is an essential process in all eukaryotic cells except yeast, including Saccharomyces cerevisiae and Schizosaccharomyces pombe. 26644575 9 57 theme glycosylation 1756:1768 arg1 type 1742:1745 this type 1737:1745 this type of O-Man glycosylation 1737:1768 It is likely that manipulation of this type of O-Man glycosylation will have wide applications for yeast bioprocessing. 26644575 7 58 theme O-GlcNAc 1403:1410 arg1 glycoproteome 1412:1424 the O-GlcNAc glycoproteome 1399:1424 the O-GlcNAc glycoproteome found in other eukaryotic cells, indicating that the two different types of O-glycosylations serve the same important biological functions 1399:1563 However, the type of yeast O-Man nucleocytoplasmic proteins and the localization of identified O-Man residues mirror that of the O-GlcNAc glycoproteome found in other eukaryotic cells, indicating that the two different types of O-glycosylations serve the same important biological functions. 26644575 5 59 theme nuclear 1117:1123 arg1 proteins 1157:1164 nuclear, cytoplasmic, and mitochondrial proteins 1117:1164 nuclear, cytoplasmic, and mitochondrial proteins in S. cerevisiae and S. pombe 1117:1194 Here, we applied the workflow to yeast with the aim to characterize the yeast O-Man glycoproteome, and in doing so, we discovered hitherto unknown O-Man glycosites on nuclear, cytoplasmic, and mitochondrial proteins in S. cerevisiae and S. pombe. 26644575 3 60 theme phosphorylation 619:633 arg1 system 645:650 its similar phosphorylation signaling system 607:650 its similar phosphorylation signaling system 607:650 A longstanding conundrum has been how yeast survives without O-GlcNAcylation in light of its similar phosphorylation signaling system. 26644575 4 61 theme O-linked 770:777 arg1 glycoproteome 795:807 the human O-linked mannose (O-Man) glycoproteome 760:807 the human O-linked mannose (O-Man) glycoproteome 760:807 We previously developed a sensitive lectin enrichment and mass spectrometry workflow for identification of the human O-linked mannose (O-Man) glycoproteome and used this to identify a pleothora of O-Man glycoproteins in human cell lines including the large family of cadherins and protocadherins. 26644575 5 62 theme unknown 1089:1095 arg1 glycosites 1103:1112 hitherto unknown O-Man glycosites 1080:1112 hitherto unknown O-Man glycosites 1080:1112 Here, we applied the workflow to yeast with the aim to characterize the yeast O-Man glycoproteome, and in doing so, we discovered hitherto unknown O-Man glycosites on nuclear, cytoplasmic, and mitochondrial proteins in S. cerevisiae and S. pombe. 26644575 1 63 from process 182:188 arg1 cerevisiae 252:261 Saccharomyces cerevisiae 238:261 Saccharomyces cerevisiae 238:261 Dynamic cycling of N-Acetylglucosamine (GlcNAc) on serine and threonine residues (O-GlcNAcylation) is an essential process in all eukaryotic cells except yeast, including Saccharomyces cerevisiae and Schizosaccharomyces pombe. 26644575 1 63 from process 182:188 arg1 pombe 287:291 Schizosaccharomyces pombe 267:291 Schizosaccharomyces pombe 267:291 Dynamic cycling of N-Acetylglucosamine (GlcNAc) on serine and threonine residues (O-GlcNAcylation) is an essential process in all eukaryotic cells except yeast, including Saccharomyces cerevisiae and Schizosaccharomyces pombe. 26644575 1 63 from process 182:188 arg1 cells 208:212 all eukaryotic cells 193:212 all eukaryotic cells 193:212 Dynamic cycling of N-Acetylglucosamine (GlcNAc) on serine and threonine residues (O-GlcNAcylation) is an essential process in all eukaryotic cells except yeast, including Saccharomyces cerevisiae and Schizosaccharomyces pombe. 26644575 9 64 theme yeast 1802:1806 arg1 bioprocessing 1808:1820 yeast bioprocessing 1802:1820 yeast bioprocessing 1802:1820 It is likely that manipulation of this type of O-Man glycosylation will have wide applications for yeast bioprocessing. 26644575 7 65 theme O-Man 1369:1373 arg1 residues 1375:1382 identified O-Man residues 1358:1382 identified O-Man residues 1358:1382 However, the type of yeast O-Man nucleocytoplasmic proteins and the localization of identified O-Man residues mirror that of the O-GlcNAc glycoproteome found in other eukaryotic cells, indicating that the two different types of O-glycosylations serve the same important biological functions. 26644575 4 66 from pleothora 837:845 arg1 family 910:915 the large family 900:915 the large family of cadherins and protocadherins 900:947 We previously developed a sensitive lectin enrichment and mass spectrometry workflow for identification of the human O-linked mannose (O-Man) glycoproteome and used this to identify a pleothora of O-Man glycoproteins in human cell lines including the large family of cadherins and protocadherins. 26644575 4 66 from pleothora 837:845 arg1 lines 884:888 human cell lines 873:888 human cell lines including the large family of cadherins and protocadherins 873:947 We previously developed a sensitive lectin enrichment and mass spectrometry workflow for identification of the human O-linked mannose (O-Man) glycoproteome and used this to identify a pleothora of O-Man glycoproteins in human cell lines including the large family of cadherins and protocadherins. 26644575 5 67 theme cytoplasmic 1126:1136 arg1 proteins 1157:1164 nuclear, cytoplasmic, and mitochondrial proteins 1117:1164 nuclear, cytoplasmic, and mitochondrial proteins in S. cerevisiae and S. pombe 1117:1194 Here, we applied the workflow to yeast with the aim to characterize the yeast O-Man glycoproteome, and in doing so, we discovered hitherto unknown O-Man glycosites on nuclear, cytoplasmic, and mitochondrial proteins in S. cerevisiae and S. pombe. 26644575 1 68 dep serine 118:123 arg1 residues 139:146 residues 139:146 residues 139:146 Dynamic cycling of N-Acetylglucosamine (GlcNAc) on serine and threonine residues (O-GlcNAcylation) is an essential process in all eukaryotic cells except yeast, including Saccharomyces cerevisiae and Schizosaccharomyces pombe. 26644575 1 69 from threonine 129:137 arg1 cycling 75:81 Dynamic cycling 67:81 Dynamic cycling of N-Acetylglucosamine (GlcNAc) on serine and threonine residues (O-GlcNAcylation) 67:164 Dynamic cycling of N-Acetylglucosamine (GlcNAc) on serine and threonine residues (O-GlcNAcylation) is an essential process in all eukaryotic cells except yeast, including Saccharomyces cerevisiae and Schizosaccharomyces pombe. 26644575 1 69 from threonine 129:137 arg1 process 182:188 an essential process 169:188 an essential process in all eukaryotic cells except yeast, including Saccharomyces cerevisiae and Schizosaccharomyces pombe 169:291 Dynamic cycling of N-Acetylglucosamine (GlcNAc) on serine and threonine residues (O-GlcNAcylation) is an essential process in all eukaryotic cells except yeast, including Saccharomyces cerevisiae and Schizosaccharomyces pombe. 26644575 1 70 theme N-Acetylglucosamine 86:104 arg1 cycling 75:81 Dynamic cycling 67:81 Dynamic cycling of N-Acetylglucosamine (GlcNAc) on serine and threonine residues (O-GlcNAcylation) 67:164 Dynamic cycling of N-Acetylglucosamine (GlcNAc) on serine and threonine residues (O-GlcNAcylation) is an essential process in all eukaryotic cells except yeast, including Saccharomyces cerevisiae and Schizosaccharomyces pombe. 26644575 1 70 theme N-Acetylglucosamine 86:104 arg1 process 182:188 an essential process 169:188 an essential process in all eukaryotic cells except yeast, including Saccharomyces cerevisiae and Schizosaccharomyces pombe 169:291 Dynamic cycling of N-Acetylglucosamine (GlcNAc) on serine and threonine residues (O-GlcNAcylation) is an essential process in all eukaryotic cells except yeast, including Saccharomyces cerevisiae and Schizosaccharomyces pombe. 26644575 2 71 theme hexosamine 463:472 arg1 pathway 487:493 the hexosamine biosynthetic pathway 459:493 the hexosamine biosynthetic pathway 459:493 O-GlcNAcylation modulates signaling and cellular processes in an intricate interplay with protein phosphorylation and serves as a key sensor of nutrients by linking the hexosamine biosynthetic pathway to cellular signaling. 26644575 6 72 located found 1231:1235 arg2 glycoproteins 1208:1220 Such O-Man glycoproteins 1197:1220 Such O-Man glycoproteins 1197:1220 Such O-Man glycoproteins were not found in our analysis of human cell lines. 26644575 6 72 located found 1231:1235 arg1 analysis 1244:1251 our analysis 1240:1251 our analysis of human cell lines 1240:1271 Such O-Man glycoproteins were not found in our analysis of human cell lines. 26644575 0 73 theme nucleocytoplasmic 15:31 arg1 O-mannose 33:41 a nucleocytoplasmic O-mannose 13:41 a nucleocytoplasmic O-mannose 13:41 Discovery of a nucleocytoplasmic O-mannose glycoproteome in yeast. 26644575 1 74 from serine 118:123 arg1 cycling 75:81 Dynamic cycling 67:81 Dynamic cycling of N-Acetylglucosamine (GlcNAc) on serine and threonine residues (O-GlcNAcylation) 67:164 Dynamic cycling of N-Acetylglucosamine (GlcNAc) on serine and threonine residues (O-GlcNAcylation) is an essential process in all eukaryotic cells except yeast, including Saccharomyces cerevisiae and Schizosaccharomyces pombe. 26644575 1 74 from serine 118:123 arg1 process 182:188 an essential process 169:188 an essential process in all eukaryotic cells except yeast, including Saccharomyces cerevisiae and Schizosaccharomyces pombe 169:291 Dynamic cycling of N-Acetylglucosamine (GlcNAc) on serine and threonine residues (O-GlcNAcylation) is an essential process in all eukaryotic cells except yeast, including Saccharomyces cerevisiae and Schizosaccharomyces pombe. 26644575 7 75 theme nucleocytoplasmic 1307:1323 arg1 proteins 1325:1332 yeast O-Man nucleocytoplasmic proteins 1295:1332 yeast O-Man nucleocytoplasmic proteins 1295:1332 However, the type of yeast O-Man nucleocytoplasmic proteins and the localization of identified O-Man residues mirror that of the O-GlcNAc glycoproteome found in other eukaryotic cells, indicating that the two different types of O-glycosylations serve the same important biological functions. 26644575 2 76 theme nutrients 438:446 arg1 O-GlcNAcylation 294:308 O-GlcNAcylation 294:308 O-GlcNAcylation 294:308 O-GlcNAcylation modulates signaling and cellular processes in an intricate interplay with protein phosphorylation and serves as a key sensor of nutrients by linking the hexosamine biosynthetic pathway to cellular signaling. 26644575 2 76 theme nutrients 438:446 arg1 sensor 428:433 a key sensor 422:433 a key sensor of nutrients 422:446 O-GlcNAcylation modulates signaling and cellular processes in an intricate interplay with protein phosphorylation and serves as a key sensor of nutrients by linking the hexosamine biosynthetic pathway to cellular signaling. 26644575 7 77 theme yeast 1295:1299 arg1 proteins 1325:1332 yeast O-Man nucleocytoplasmic proteins 1295:1332 yeast O-Man nucleocytoplasmic proteins 1295:1332 However, the type of yeast O-Man nucleocytoplasmic proteins and the localization of identified O-Man residues mirror that of the O-GlcNAc glycoproteome found in other eukaryotic cells, indicating that the two different types of O-glycosylations serve the same important biological functions. 26644575 2 78 theme cellular 498:505 arg1 signaling 507:515 cellular signaling 498:515 cellular signaling 498:515 O-GlcNAcylation modulates signaling and cellular processes in an intricate interplay with protein phosphorylation and serves as a key sensor of nutrients by linking the hexosamine biosynthetic pathway to cellular signaling. 26644575 8 79 theme enzymatic 1609:1617 arg1 machinery 1619:1627 the enzymatic machinery 1605:1627 the enzymatic machinery that is predicted to regulate the nucleocytoplasmic O-Man glycosylations 1605:1700 The discovery opens for exploration of the enzymatic machinery that is predicted to regulate the nucleocytoplasmic O-Man glycosylations. 26644575 4 80 theme cell 879:882 arg1 family 910:915 the large family 900:915 the large family of cadherins and protocadherins 900:947 We previously developed a sensitive lectin enrichment and mass spectrometry workflow for identification of the human O-linked mannose (O-Man) glycoproteome and used this to identify a pleothora of O-Man glycoproteins in human cell lines including the large family of cadherins and protocadherins. 26644575 4 80 theme cell 879:882 arg1 lines 884:888 human cell lines 873:888 human cell lines including the large family of cadherins and protocadherins 873:947 We previously developed a sensitive lectin enrichment and mass spectrometry workflow for identification of the human O-linked mannose (O-Man) glycoproteome and used this to identify a pleothora of O-Man glycoproteins in human cell lines including the large family of cadherins and protocadherins. 26644575 2 81 theme intricate 359:367 arg1 interplay 369:377 an intricate interplay 356:377 an intricate interplay with protein phosphorylation 356:406 O-GlcNAcylation modulates signaling and cellular processes in an intricate interplay with protein phosphorylation and serves as a key sensor of nutrients by linking the hexosamine biosynthetic pathway to cellular signaling. 26644575 7 82 theme biological 1544:1553 arg1 functions 1555:1563 the same important biological functions 1525:1563 the same important biological functions 1525:1563 However, the type of yeast O-Man nucleocytoplasmic proteins and the localization of identified O-Man residues mirror that of the O-GlcNAc glycoproteome found in other eukaryotic cells, indicating that the two different types of O-glycosylations serve the same important biological functions. 26644575 5 83 theme O-Man 1028:1032 arg1 glycoproteome 1034:1046 the yeast O-Man glycoproteome 1018:1046 the yeast O-Man glycoproteome 1018:1046 Here, we applied the workflow to yeast with the aim to characterize the yeast O-Man glycoproteome, and in doing so, we discovered hitherto unknown O-Man glycosites on nuclear, cytoplasmic, and mitochondrial proteins in S. cerevisiae and S. pombe. 26644575 1 84 from N-Acetylglucosamine 86:104 arg1 threonine 129:137 threonine 129:137 threonine 129:137 Dynamic cycling of N-Acetylglucosamine (GlcNAc) on serine and threonine residues (O-GlcNAcylation) is an essential process in all eukaryotic cells except yeast, including Saccharomyces cerevisiae and Schizosaccharomyces pombe. 26644575 1 84 from N-Acetylglucosamine 86:104 arg1 serine 118:123 serine 118:123 serine 118:123 Dynamic cycling of N-Acetylglucosamine (GlcNAc) on serine and threonine residues (O-GlcNAcylation) is an essential process in all eukaryotic cells except yeast, including Saccharomyces cerevisiae and Schizosaccharomyces pombe. 26644575 7 85 theme same 1529:1532 arg1 functions 1555:1563 the same important biological functions 1525:1563 the same important biological functions 1525:1563 However, the type of yeast O-Man nucleocytoplasmic proteins and the localization of identified O-Man residues mirror that of the O-GlcNAc glycoproteome found in other eukaryotic cells, indicating that the two different types of O-glycosylations serve the same important biological functions. 26644575 4 86 theme O-Man 850:854 arg1 glycoproteins 856:868 O-Man glycoproteins 850:868 O-Man glycoproteins 850:868 We previously developed a sensitive lectin enrichment and mass spectrometry workflow for identification of the human O-linked mannose (O-Man) glycoproteome and used this to identify a pleothora of O-Man glycoproteins in human cell lines including the large family of cadherins and protocadherins. 26644575 1 87 from cycling 75:81 arg1 threonine 129:137 threonine 129:137 threonine 129:137 Dynamic cycling of N-Acetylglucosamine (GlcNAc) on serine and threonine residues (O-GlcNAcylation) is an essential process in all eukaryotic cells except yeast, including Saccharomyces cerevisiae and Schizosaccharomyces pombe. 26644575 1 87 from cycling 75:81 arg1 serine 118:123 serine 118:123 serine 118:123 Dynamic cycling of N-Acetylglucosamine (GlcNAc) on serine and threonine residues (O-GlcNAcylation) is an essential process in all eukaryotic cells except yeast, including Saccharomyces cerevisiae and Schizosaccharomyces pombe. 26359231 6 0 theme predifferentiation 1144:1161 arg1 A/C 1169:1171 predifferentiation lamin A/C 1144:1171 predifferentiation lamin A/C LADs 1144:1176 Accordingly, whereas predifferentiation lamin A/C LADs are gene-rich, post-differentiation LADs harbor repressive features reminiscent of lamin B1 LADs. 26359231 2 1 theme H2B 379:381 arg1 domains 360:366 domains 360:366 domains of histone H2B modified on serine 112 by the nutrient sensor O-linked N-acetylglucosamine (H2BS112GlcNAc), which we term GADs 360:492 Here, we provide evidence for prepatterning of differentiation-driven formation of lamin A/C LADs by domains of histone H2B modified on serine 112 by the nutrient sensor O-linked N-acetylglucosamine (H2BS112GlcNAc), which we term GADs. 26359231 2 1 theme H2B 379:381 arg1 H2B 379:381 histone H2B 371:381 histone H2B modified on serine 112 by the nutrient sensor O-linked N-acetylglucosamine (H2BS112GlcNAc), which we term GADs 371:492 Here, we provide evidence for prepatterning of differentiation-driven formation of lamin A/C LADs by domains of histone H2B modified on serine 112 by the nutrient sensor O-linked N-acetylglucosamine (H2BS112GlcNAc), which we term GADs. 26359231 6 2 theme lamin 1261:1265 arg1 B1 1267:1268 lamin B1 1261:1268 lamin B1 LADs 1261:1273 Accordingly, whereas predifferentiation lamin A/C LADs are gene-rich, post-differentiation LADs harbor repressive features reminiscent of lamin B1 LADs. 26359231 3 3 theme in 563:564 arg1 adipogenesis 572:583 in vitro adipogenesis 563:583 in vitro adipogenesis 563:583 We demonstrate a two-step process of lamin A/C LAD formation during in vitro adipogenesis, involving spreading of lamin A/C-chromatin interactions in the transition from progenitor cell proliferation to cell-cycle arrest, and genome-scale redistribution of these interactions through a process of LAD exchange within hours of adipogenic induction. 26359231 4 4 theme active 876:881 arg1 contexts 908:915 active and repressive chromatin contexts 876:915 active and repressive chromatin contexts that can be influenced by cell differentiation status 876:969 Lamin A/C LADs are found both in active and repressive chromatin contexts that can be influenced by cell differentiation status. 26359231 6 5 theme reminiscent 1246:1256 arg1 features 1237:1244 repressive features 1226:1244 repressive features reminiscent of lamin B1 LADs 1226:1273 Accordingly, whereas predifferentiation lamin A/C LADs are gene-rich, post-differentiation LADs harbor repressive features reminiscent of lamin B1 LADs. 26359231 3 6 from proliferation 681:693 arg1 interactions 629:640 lamin A/C-chromatin interactions 609:640 lamin A/C-chromatin interactions in the transition from progenitor cell proliferation to cell-cycle arrest 609:714 We demonstrate a two-step process of lamin A/C LAD formation during in vitro adipogenesis, involving spreading of lamin A/C-chromatin interactions in the transition from progenitor cell proliferation to cell-cycle arrest, and genome-scale redistribution of these interactions through a process of LAD exchange within hours of adipogenic induction. 26359231 3 6 from proliferation 681:693 arg1 transition 649:658 the transition 645:658 the transition from progenitor cell proliferation to cell-cycle arrest 645:714 We demonstrate a two-step process of lamin A/C LAD formation during in vitro adipogenesis, involving spreading of lamin A/C-chromatin interactions in the transition from progenitor cell proliferation to cell-cycle arrest, and genome-scale redistribution of these interactions through a process of LAD exchange within hours of adipogenic induction. 26359231 3 7 theme formation 546:554 arg1 process 521:527 a two-step process 510:527 a two-step process of lamin A/C LAD formation 510:554 We demonstrate a two-step process of lamin A/C LAD formation during in vitro adipogenesis, involving spreading of lamin A/C-chromatin interactions in the transition from progenitor cell proliferation to cell-cycle arrest, and genome-scale redistribution of these interactions through a process of LAD exchange within hours of adipogenic induction. 26359231 1 8 with interactions 124:135 arg1 chromatin 160:168 chromatin 160:168 chromatin through lamin-associated domains (LADs) 160:208 Dynamic interactions of nuclear lamins with chromatin through lamin-associated domains (LADs) contribute to spatial arrangement of the genome. 26359231 4 9 theme repressive 887:896 arg1 contexts 908:915 active and repressive chromatin contexts 876:915 active and repressive chromatin contexts that can be influenced by cell differentiation status 876:969 Lamin A/C LADs are found both in active and repressive chromatin contexts that can be influenced by cell differentiation status. 26359231 6 10 theme repressive 1226:1235 arg1 features 1237:1244 repressive features 1226:1244 repressive features reminiscent of lamin B1 LADs 1226:1273 Accordingly, whereas predifferentiation lamin A/C LADs are gene-rich, post-differentiation LADs harbor repressive features reminiscent of lamin B1 LADs. 26359231 3 11 theme LAD 792:794 arg1 exchange 796:803 LAD exchange 792:803 LAD exchange 792:803 We demonstrate a two-step process of lamin A/C LAD formation during in vitro adipogenesis, involving spreading of lamin A/C-chromatin interactions in the transition from progenitor cell proliferation to cell-cycle arrest, and genome-scale redistribution of these interactions through a process of LAD exchange within hours of adipogenic induction. 26359231 2 12 theme A/C 348:350 arg1 formation 329:337 differentiation-driven formation 306:337 differentiation-driven formation of lamin A/C LADs 306:355 Here, we provide evidence for prepatterning of differentiation-driven formation of lamin A/C LADs by domains of histone H2B modified on serine 112 by the nutrient sensor O-linked N-acetylglucosamine (H2BS112GlcNAc), which we term GADs. 26359231 8 13 theme adipogenic 1544:1553 arg1 LADs 1555:1558 adipogenic LADs 1544:1558 adipogenic LADs 1544:1558 Our results unveil an epigenetic prepatterning of adipogenic LADs by GADs, suggesting a coupling of developmentally regulated lamin A/C-genome interactions to a metabolically sensitive chromatin modification. 26359231 7 14 theme O-GlcNAc 1476:1483 arg1 cycling 1485:1491 O-GlcNAc cycling 1476:1491 O-GlcNAc cycling 1476:1491 Release of lamin A/C from genes directly involved in glycolysis concurs with their transcriptional up-regulation after adipogenic induction, and with downstream elevations in H2BS112GlcNAc levels and O-GlcNAc cycling. 26359231 3 15 theme A/C-chromatin 615:627 arg1 interactions 629:640 lamin A/C-chromatin interactions 609:640 lamin A/C-chromatin interactions in the transition from progenitor cell proliferation to cell-cycle arrest 609:714 We demonstrate a two-step process of lamin A/C LAD formation during in vitro adipogenesis, involving spreading of lamin A/C-chromatin interactions in the transition from progenitor cell proliferation to cell-cycle arrest, and genome-scale redistribution of these interactions through a process of LAD exchange within hours of adipogenic induction. 26359231 5 16 theme intergenic 1078:1087 arg1 domains 1114:1120 megabase-size intergenic and repressive chromatin domains 1064:1120 megabase-size intergenic and repressive chromatin domains 1064:1120 De novo formation of adipogenic lamin A/C LADs occurs nonrandomly on GADs, which consist of megabase-size intergenic and repressive chromatin domains. 26359231 1 17 theme lamins 148:153 arg1 interactions 124:135 Dynamic interactions 116:135 Dynamic interactions of nuclear lamins with chromatin through lamin-associated domains (LADs) 116:208 Dynamic interactions of nuclear lamins with chromatin through lamin-associated domains (LADs) contribute to spatial arrangement of the genome. 26359231 4 18 theme cell 943:946 arg1 status 964:969 cell differentiation status 943:969 cell differentiation status 943:969 Lamin A/C LADs are found both in active and repressive chromatin contexts that can be influenced by cell differentiation status. 26359231 5 19 theme repressive 1093:1102 arg1 domains 1114:1120 megabase-size intergenic and repressive chromatin domains 1064:1120 megabase-size intergenic and repressive chromatin domains 1064:1120 De novo formation of adipogenic lamin A/C LADs occurs nonrandomly on GADs, which consist of megabase-size intergenic and repressive chromatin domains. 26359231 3 20 dep in 563:564 arg1 vitro 566:570 vitro 566:570 vitro 566:570 We demonstrate a two-step process of lamin A/C LAD formation during in vitro adipogenesis, involving spreading of lamin A/C-chromatin interactions in the transition from progenitor cell proliferation to cell-cycle arrest, and genome-scale redistribution of these interactions through a process of LAD exchange within hours of adipogenic induction. 26359231 7 21 theme downstream 1426:1435 arg1 elevations 1437:1446 downstream elevations 1426:1446 downstream elevations in H2BS112GlcNAc levels and O-GlcNAc cycling 1426:1491 Release of lamin A/C from genes directly involved in glycolysis concurs with their transcriptional up-regulation after adipogenic induction, and with downstream elevations in H2BS112GlcNAc levels and O-GlcNAc cycling. 26359231 3 22 theme induction 832:840 arg1 hours 812:816 hours 812:816 hours of adipogenic induction 812:840 We demonstrate a two-step process of lamin A/C LAD formation during in vitro adipogenesis, involving spreading of lamin A/C-chromatin interactions in the transition from progenitor cell proliferation to cell-cycle arrest, and genome-scale redistribution of these interactions through a process of LAD exchange within hours of adipogenic induction. 26359231 1 23 theme lamin-associated 178:193 arg1 LADs 204:207 LADs 204:207 LADs 204:207 Dynamic interactions of nuclear lamins with chromatin through lamin-associated domains (LADs) contribute to spatial arrangement of the genome. 26359231 1 23 theme lamin-associated 178:193 arg1 domains 195:201 lamin-associated domains 178:201 lamin-associated domains (LADs) 178:208 Dynamic interactions of nuclear lamins with chromatin through lamin-associated domains (LADs) contribute to spatial arrangement of the genome. 26359231 0 24 theme histone 103:109 arg1 H2B 111:113 GlcNAcylated histone H2B 90:113 GlcNAcylated histone H2B 90:113 Prepatterning of differentiation-driven nuclear lamin A/C-associated chromatin domains by GlcNAcylated histone H2B. 26359231 8 25 theme regulated 1610:1618 arg1 interactions 1637:1648 developmentally regulated lamin A/C-genome interactions 1594:1648 developmentally regulated lamin A/C-genome interactions 1594:1648 Our results unveil an epigenetic prepatterning of adipogenic LADs by GADs, suggesting a coupling of developmentally regulated lamin A/C-genome interactions to a metabolically sensitive chromatin modification. 26359231 2 26 theme differentiation-driven 306:327 arg1 formation 329:337 differentiation-driven formation 306:337 differentiation-driven formation of lamin A/C LADs 306:355 Here, we provide evidence for prepatterning of differentiation-driven formation of lamin A/C LADs by domains of histone H2B modified on serine 112 by the nutrient sensor O-linked N-acetylglucosamine (H2BS112GlcNAc), which we term GADs. 26359231 5 27 theme A/C 1010:1012 arg1 formation 980:988 De novo formation 972:988 De novo formation of adipogenic lamin A/C 972:1012 De novo formation of adipogenic lamin A/C LADs occurs nonrandomly on GADs, which consist of megabase-size intergenic and repressive chromatin domains. 26359231 5 28 theme De 972:973 arg1 formation 980:988 De novo formation 972:988 De novo formation of adipogenic lamin A/C 972:1012 De novo formation of adipogenic lamin A/C LADs occurs nonrandomly on GADs, which consist of megabase-size intergenic and repressive chromatin domains. 26359231 8 29 theme A/C-genome 1626:1635 arg1 interactions 1637:1648 developmentally regulated lamin A/C-genome interactions 1594:1648 developmentally regulated lamin A/C-genome interactions 1594:1648 Our results unveil an epigenetic prepatterning of adipogenic LADs by GADs, suggesting a coupling of developmentally regulated lamin A/C-genome interactions to a metabolically sensitive chromatin modification. 26359231 2 30 theme nutrient 413:420 arg1 H2BS112GlcNAc 459:471 H2BS112GlcNAc 459:471 H2BS112GlcNAc 459:471 Here, we provide evidence for prepatterning of differentiation-driven formation of lamin A/C LADs by domains of histone H2B modified on serine 112 by the nutrient sensor O-linked N-acetylglucosamine (H2BS112GlcNAc), which we term GADs. 26359231 2 30 theme nutrient 413:420 arg1 N-acetylglucosamine 438:456 the nutrient sensor O-linked N-acetylglucosamine 409:456 the nutrient sensor O-linked N-acetylglucosamine (H2BS112GlcNAc) 409:472 Here, we provide evidence for prepatterning of differentiation-driven formation of lamin A/C LADs by domains of histone H2B modified on serine 112 by the nutrient sensor O-linked N-acetylglucosamine (H2BS112GlcNAc), which we term GADs. 26359231 0 31 theme GlcNAcylated 90:101 arg1 H2B 111:113 GlcNAcylated histone H2B 90:113 GlcNAcylated histone H2B 90:113 Prepatterning of differentiation-driven nuclear lamin A/C-associated chromatin domains by GlcNAcylated histone H2B. 26359231 3 32 from transition 649:658 arg1 redistribution 734:747 genome-scale redistribution 721:747 genome-scale redistribution of these interactions 721:769 We demonstrate a two-step process of lamin A/C LAD formation during in vitro adipogenesis, involving spreading of lamin A/C-chromatin interactions in the transition from progenitor cell proliferation to cell-cycle arrest, and genome-scale redistribution of these interactions through a process of LAD exchange within hours of adipogenic induction. 26359231 3 32 from transition 649:658 arg1 spreading 596:604 spreading 596:604 spreading of lamin A/C-chromatin interactions in the transition from progenitor cell proliferation to cell-cycle arrest 596:714 We demonstrate a two-step process of lamin A/C LAD formation during in vitro adipogenesis, involving spreading of lamin A/C-chromatin interactions in the transition from progenitor cell proliferation to cell-cycle arrest, and genome-scale redistribution of these interactions through a process of LAD exchange within hours of adipogenic induction. 26359231 1 33 theme Dynamic 116:122 arg1 interactions 124:135 Dynamic interactions 116:135 Dynamic interactions of nuclear lamins with chromatin through lamin-associated domains (LADs) 116:208 Dynamic interactions of nuclear lamins with chromatin through lamin-associated domains (LADs) contribute to spatial arrangement of the genome. 26359231 6 34 theme LADs 1270:1273 arg1 reminiscent 1246:1256 reminiscent 1246:1256 reminiscent 1246:1256 Accordingly, whereas predifferentiation lamin A/C LADs are gene-rich, post-differentiation LADs harbor repressive features reminiscent of lamin B1 LADs. 26359231 0 35 theme differentiation-driven 17:38 arg1 domains 79:85 differentiation-driven nuclear lamin A/C-associated chromatin domains 17:85 differentiation-driven nuclear lamin A/C-associated chromatin domains 17:85 Prepatterning of differentiation-driven nuclear lamin A/C-associated chromatin domains by GlcNAcylated histone H2B. 26359231 5 36 theme adipogenic 993:1002 arg1 A/C 1010:1012 adipogenic lamin A/C 993:1012 adipogenic lamin A/C 993:1012 De novo formation of adipogenic lamin A/C LADs occurs nonrandomly on GADs, which consist of megabase-size intergenic and repressive chromatin domains. 26359231 7 37 theme adipogenic 1395:1404 arg1 induction 1406:1414 adipogenic induction 1395:1414 adipogenic induction 1395:1414 Release of lamin A/C from genes directly involved in glycolysis concurs with their transcriptional up-regulation after adipogenic induction, and with downstream elevations in H2BS112GlcNAc levels and O-GlcNAc cycling. 26359231 8 38 theme chromatin 1679:1687 arg1 modification 1689:1700 a metabolically sensitive chromatin modification 1653:1700 a metabolically sensitive chromatin modification 1653:1700 Our results unveil an epigenetic prepatterning of adipogenic LADs by GADs, suggesting a coupling of developmentally regulated lamin A/C-genome interactions to a metabolically sensitive chromatin modification. 26359231 2 39 theme O-linked 429:436 arg1 H2BS112GlcNAc 459:471 H2BS112GlcNAc 459:471 H2BS112GlcNAc 459:471 Here, we provide evidence for prepatterning of differentiation-driven formation of lamin A/C LADs by domains of histone H2B modified on serine 112 by the nutrient sensor O-linked N-acetylglucosamine (H2BS112GlcNAc), which we term GADs. 26359231 2 39 theme O-linked 429:436 arg1 N-acetylglucosamine 438:456 the nutrient sensor O-linked N-acetylglucosamine 409:456 the nutrient sensor O-linked N-acetylglucosamine (H2BS112GlcNAc) 409:472 Here, we provide evidence for prepatterning of differentiation-driven formation of lamin A/C LADs by domains of histone H2B modified on serine 112 by the nutrient sensor O-linked N-acetylglucosamine (H2BS112GlcNAc), which we term GADs. 26359231 0 40 theme lamin 48:52 arg1 domains 79:85 differentiation-driven nuclear lamin A/C-associated chromatin domains 17:85 differentiation-driven nuclear lamin A/C-associated chromatin domains 17:85 Prepatterning of differentiation-driven nuclear lamin A/C-associated chromatin domains by GlcNAcylated histone H2B. 26359231 3 41 theme progenitor 665:674 arg1 proliferation 681:693 progenitor cell proliferation 665:693 progenitor cell proliferation 665:693 We demonstrate a two-step process of lamin A/C LAD formation during in vitro adipogenesis, involving spreading of lamin A/C-chromatin interactions in the transition from progenitor cell proliferation to cell-cycle arrest, and genome-scale redistribution of these interactions through a process of LAD exchange within hours of adipogenic induction. 26359231 2 42 theme histone 371:377 arg1 H2B 379:381 histone H2B 371:381 histone H2B modified on serine 112 by the nutrient sensor O-linked N-acetylglucosamine (H2BS112GlcNAc), which we term GADs 371:492 Here, we provide evidence for prepatterning of differentiation-driven formation of lamin A/C LADs by domains of histone H2B modified on serine 112 by the nutrient sensor O-linked N-acetylglucosamine (H2BS112GlcNAc), which we term GADs. 26359231 0 43 theme chromatin 69:77 arg1 domains 79:85 differentiation-driven nuclear lamin A/C-associated chromatin domains 17:85 differentiation-driven nuclear lamin A/C-associated chromatin domains 17:85 Prepatterning of differentiation-driven nuclear lamin A/C-associated chromatin domains by GlcNAcylated histone H2B. 26359231 5 44 theme megabase-size 1064:1076 arg1 domains 1114:1120 megabase-size intergenic and repressive chromatin domains 1064:1120 megabase-size intergenic and repressive chromatin domains 1064:1120 De novo formation of adipogenic lamin A/C LADs occurs nonrandomly on GADs, which consist of megabase-size intergenic and repressive chromatin domains. 26359231 8 45 theme epigenetic 1516:1525 arg1 prepatterning 1527:1539 an epigenetic prepatterning 1513:1539 an epigenetic prepatterning of adipogenic LADs by GADs 1513:1566 Our results unveil an epigenetic prepatterning of adipogenic LADs by GADs, suggesting a coupling of developmentally regulated lamin A/C-genome interactions to a metabolically sensitive chromatin modification. 26359231 1 46 theme genome 251:256 arg1 arrangement 232:242 spatial arrangement 224:242 spatial arrangement of the genome 224:256 Dynamic interactions of nuclear lamins with chromatin through lamin-associated domains (LADs) contribute to spatial arrangement of the genome. 26359231 3 47 theme cell-cycle 698:707 arg1 arrest 709:714 cell-cycle arrest 698:714 cell-cycle arrest 698:714 We demonstrate a two-step process of lamin A/C LAD formation during in vitro adipogenesis, involving spreading of lamin A/C-chromatin interactions in the transition from progenitor cell proliferation to cell-cycle arrest, and genome-scale redistribution of these interactions through a process of LAD exchange within hours of adipogenic induction. 26359231 4 48 theme A/C 849:851 arg1 LADs 853:856 Lamin A/C LADs 843:856 Lamin A/C LADs 843:856 Lamin A/C LADs are found both in active and repressive chromatin contexts that can be influenced by cell differentiation status. 26359231 3 49 theme lamin 532:536 arg1 A/C 538:540 lamin A/C 532:540 lamin A/C LAD formation 532:554 We demonstrate a two-step process of lamin A/C LAD formation during in vitro adipogenesis, involving spreading of lamin A/C-chromatin interactions in the transition from progenitor cell proliferation to cell-cycle arrest, and genome-scale redistribution of these interactions through a process of LAD exchange within hours of adipogenic induction. 26359231 4 50 dep contexts 908:915 arg1 both 868:871 both 868:871 both 868:871 Lamin A/C LADs are found both in active and repressive chromatin contexts that can be influenced by cell differentiation status. 26359231 6 51 theme lamin 1163:1167 arg1 A/C 1169:1171 predifferentiation lamin A/C 1144:1171 predifferentiation lamin A/C LADs 1144:1176 Accordingly, whereas predifferentiation lamin A/C LADs are gene-rich, post-differentiation LADs harbor repressive features reminiscent of lamin B1 LADs. 26359231 4 52 theme chromatin 898:906 arg1 contexts 908:915 active and repressive chromatin contexts 876:915 active and repressive chromatin contexts that can be influenced by cell differentiation status 876:969 Lamin A/C LADs are found both in active and repressive chromatin contexts that can be influenced by cell differentiation status. 26359231 7 53 from genes 1302:1306 arg1 Release 1276:1282 Release 1276:1282 Release of lamin A/C from genes directly involved in glycolysis 1276:1338 Release of lamin A/C from genes directly involved in glycolysis concurs with their transcriptional up-regulation after adipogenic induction, and with downstream elevations in H2BS112GlcNAc levels and O-GlcNAc cycling. 26359231 3 54 theme genome-scale 721:732 arg1 redistribution 734:747 genome-scale redistribution 721:747 genome-scale redistribution of these interactions 721:769 We demonstrate a two-step process of lamin A/C LAD formation during in vitro adipogenesis, involving spreading of lamin A/C-chromatin interactions in the transition from progenitor cell proliferation to cell-cycle arrest, and genome-scale redistribution of these interactions through a process of LAD exchange within hours of adipogenic induction. 26359231 2 55 theme formation 329:337 arg1 prepatterning 289:301 prepatterning 289:301 prepatterning of differentiation-driven formation of lamin A/C LADs by domains of histone H2B modified on serine 112 by the nutrient sensor O-linked N-acetylglucosamine (H2BS112GlcNAc), which we term GADs 289:492 Here, we provide evidence for prepatterning of differentiation-driven formation of lamin A/C LADs by domains of histone H2B modified on serine 112 by the nutrient sensor O-linked N-acetylglucosamine (H2BS112GlcNAc), which we term GADs. 26359231 3 56 theme LAD 542:544 arg1 formation 546:554 lamin A/C LAD formation 532:554 lamin A/C LAD formation 532:554 We demonstrate a two-step process of lamin A/C LAD formation during in vitro adipogenesis, involving spreading of lamin A/C-chromatin interactions in the transition from progenitor cell proliferation to cell-cycle arrest, and genome-scale redistribution of these interactions through a process of LAD exchange within hours of adipogenic induction. 26359231 3 57 theme interactions 758:769 arg1 redistribution 734:747 genome-scale redistribution 721:747 genome-scale redistribution of these interactions 721:769 We demonstrate a two-step process of lamin A/C LAD formation during in vitro adipogenesis, involving spreading of lamin A/C-chromatin interactions in the transition from progenitor cell proliferation to cell-cycle arrest, and genome-scale redistribution of these interactions through a process of LAD exchange within hours of adipogenic induction. 26359231 3 57 theme interactions 758:769 arg1 spreading 596:604 spreading 596:604 spreading of lamin A/C-chromatin interactions in the transition from progenitor cell proliferation to cell-cycle arrest 596:714 We demonstrate a two-step process of lamin A/C LAD formation during in vitro adipogenesis, involving spreading of lamin A/C-chromatin interactions in the transition from progenitor cell proliferation to cell-cycle arrest, and genome-scale redistribution of these interactions through a process of LAD exchange within hours of adipogenic induction. 26359231 7 58 theme lamin 1287:1291 arg1 A/C 1293:1295 lamin A/C 1287:1295 lamin A/C 1287:1295 Release of lamin A/C from genes directly involved in glycolysis concurs with their transcriptional up-regulation after adipogenic induction, and with downstream elevations in H2BS112GlcNAc levels and O-GlcNAc cycling. 26359231 3 59 theme exchange 796:803 arg1 process 781:787 a process 779:787 a process of LAD exchange within hours of adipogenic induction 779:840 We demonstrate a two-step process of lamin A/C LAD formation during in vitro adipogenesis, involving spreading of lamin A/C-chromatin interactions in the transition from progenitor cell proliferation to cell-cycle arrest, and genome-scale redistribution of these interactions through a process of LAD exchange within hours of adipogenic induction. 26359231 2 60 theme lamin 342:346 arg1 A/C 348:350 lamin A/C LADs 342:355 lamin A/C LADs 342:355 Here, we provide evidence for prepatterning of differentiation-driven formation of lamin A/C LADs by domains of histone H2B modified on serine 112 by the nutrient sensor O-linked N-acetylglucosamine (H2BS112GlcNAc), which we term GADs. 26359231 1 61 theme spatial 224:230 arg1 arrangement 232:242 spatial arrangement 224:242 spatial arrangement of the genome 224:256 Dynamic interactions of nuclear lamins with chromatin through lamin-associated domains (LADs) contribute to spatial arrangement of the genome. 26359231 4 62 theme differentiation 948:962 arg1 status 964:969 cell differentiation status 943:969 cell differentiation status 943:969 Lamin A/C LADs are found both in active and repressive chromatin contexts that can be influenced by cell differentiation status. 26359231 8 63 theme LADs 1555:1558 arg1 prepatterning 1527:1539 an epigenetic prepatterning 1513:1539 an epigenetic prepatterning of adipogenic LADs by GADs 1513:1566 Our results unveil an epigenetic prepatterning of adipogenic LADs by GADs, suggesting a coupling of developmentally regulated lamin A/C-genome interactions to a metabolically sensitive chromatin modification. 26359231 6 64 theme post-differentiation 1193:1212 arg1 LADs 1214:1217 post-differentiation LADs 1193:1217 post-differentiation LADs 1193:1217 Accordingly, whereas predifferentiation lamin A/C LADs are gene-rich, post-differentiation LADs harbor repressive features reminiscent of lamin B1 LADs. 26359231 3 65 theme lamin 609:613 arg1 interactions 629:640 lamin A/C-chromatin interactions 609:640 lamin A/C-chromatin interactions in the transition from progenitor cell proliferation to cell-cycle arrest 609:714 We demonstrate a two-step process of lamin A/C LAD formation during in vitro adipogenesis, involving spreading of lamin A/C-chromatin interactions in the transition from progenitor cell proliferation to cell-cycle arrest, and genome-scale redistribution of these interactions through a process of LAD exchange within hours of adipogenic induction. 26359231 3 66 from redistribution 734:747 arg1 transition 649:658 the transition 645:658 the transition from progenitor cell proliferation to cell-cycle arrest 645:714 We demonstrate a two-step process of lamin A/C LAD formation during in vitro adipogenesis, involving spreading of lamin A/C-chromatin interactions in the transition from progenitor cell proliferation to cell-cycle arrest, and genome-scale redistribution of these interactions through a process of LAD exchange within hours of adipogenic induction. 26359231 3 67 theme adipogenic 821:830 arg1 induction 832:840 adipogenic induction 821:840 adipogenic induction 821:840 We demonstrate a two-step process of lamin A/C LAD formation during in vitro adipogenesis, involving spreading of lamin A/C-chromatin interactions in the transition from progenitor cell proliferation to cell-cycle arrest, and genome-scale redistribution of these interactions through a process of LAD exchange within hours of adipogenic induction. 26359231 1 68 theme nuclear 140:146 arg1 lamins 148:153 nuclear lamins 140:153 nuclear lamins 140:153 Dynamic interactions of nuclear lamins with chromatin through lamin-associated domains (LADs) contribute to spatial arrangement of the genome. 26359231 7 69 theme H2BS112GlcNAc 1451:1463 arg1 levels 1465:1470 H2BS112GlcNAc levels 1451:1470 H2BS112GlcNAc levels 1451:1470 Release of lamin A/C from genes directly involved in glycolysis concurs with their transcriptional up-regulation after adipogenic induction, and with downstream elevations in H2BS112GlcNAc levels and O-GlcNAc cycling. 26359231 7 70 theme A/C 1293:1295 arg1 Release 1276:1282 Release 1276:1282 Release of lamin A/C from genes directly involved in glycolysis 1276:1338 Release of lamin A/C from genes directly involved in glycolysis concurs with their transcriptional up-regulation after adipogenic induction, and with downstream elevations in H2BS112GlcNAc levels and O-GlcNAc cycling. 26359231 5 71 theme chromatin 1104:1112 arg1 domains 1114:1120 megabase-size intergenic and repressive chromatin domains 1064:1120 megabase-size intergenic and repressive chromatin domains 1064:1120 De novo formation of adipogenic lamin A/C LADs occurs nonrandomly on GADs, which consist of megabase-size intergenic and repressive chromatin domains. 26359231 3 72 theme interactions 629:640 arg1 redistribution 734:747 genome-scale redistribution 721:747 genome-scale redistribution of these interactions 721:769 We demonstrate a two-step process of lamin A/C LAD formation during in vitro adipogenesis, involving spreading of lamin A/C-chromatin interactions in the transition from progenitor cell proliferation to cell-cycle arrest, and genome-scale redistribution of these interactions through a process of LAD exchange within hours of adipogenic induction. 26359231 3 72 theme interactions 629:640 arg1 spreading 596:604 spreading 596:604 spreading of lamin A/C-chromatin interactions in the transition from progenitor cell proliferation to cell-cycle arrest 596:714 We demonstrate a two-step process of lamin A/C LAD formation during in vitro adipogenesis, involving spreading of lamin A/C-chromatin interactions in the transition from progenitor cell proliferation to cell-cycle arrest, and genome-scale redistribution of these interactions through a process of LAD exchange within hours of adipogenic induction. 26359231 6 73 theme B1 1267:1268 arg1 LADs 1270:1273 lamin B1 LADs 1261:1273 lamin B1 LADs 1261:1273 Accordingly, whereas predifferentiation lamin A/C LADs are gene-rich, post-differentiation LADs harbor repressive features reminiscent of lamin B1 LADs. 26359231 8 74 theme lamin 1620:1624 arg1 interactions 1637:1648 developmentally regulated lamin A/C-genome interactions 1594:1648 developmentally regulated lamin A/C-genome interactions 1594:1648 Our results unveil an epigenetic prepatterning of adipogenic LADs by GADs, suggesting a coupling of developmentally regulated lamin A/C-genome interactions to a metabolically sensitive chromatin modification. 26359231 5 75 theme lamin 1004:1008 arg1 A/C 1010:1012 adipogenic lamin A/C 993:1012 adipogenic lamin A/C 993:1012 De novo formation of adipogenic lamin A/C LADs occurs nonrandomly on GADs, which consist of megabase-size intergenic and repressive chromatin domains. 26359231 8 76 theme interactions 1637:1648 arg1 coupling 1582:1589 a coupling 1580:1589 a coupling of developmentally regulated lamin A/C-genome interactions to a metabolically sensitive chromatin modification 1580:1700 Our results unveil an epigenetic prepatterning of adipogenic LADs by GADs, suggesting a coupling of developmentally regulated lamin A/C-genome interactions to a metabolically sensitive chromatin modification. 26359231 5 77 dep De 972:973 arg1 novo 975:978 novo 975:978 novo 975:978 De novo formation of adipogenic lamin A/C LADs occurs nonrandomly on GADs, which consist of megabase-size intergenic and repressive chromatin domains. 26359231 3 78 from interactions 629:640 arg1 proliferation 681:693 progenitor cell proliferation 665:693 progenitor cell proliferation 665:693 We demonstrate a two-step process of lamin A/C LAD formation during in vitro adipogenesis, involving spreading of lamin A/C-chromatin interactions in the transition from progenitor cell proliferation to cell-cycle arrest, and genome-scale redistribution of these interactions through a process of LAD exchange within hours of adipogenic induction. 26359231 3 78 from interactions 629:640 arg1 transition 649:658 the transition 645:658 the transition from progenitor cell proliferation to cell-cycle arrest 645:714 We demonstrate a two-step process of lamin A/C LAD formation during in vitro adipogenesis, involving spreading of lamin A/C-chromatin interactions in the transition from progenitor cell proliferation to cell-cycle arrest, and genome-scale redistribution of these interactions through a process of LAD exchange within hours of adipogenic induction. 26359231 7 79 from elevations 1437:1446 arg1 levels 1465:1470 H2BS112GlcNAc levels 1451:1470 H2BS112GlcNAc levels 1451:1470 Release of lamin A/C from genes directly involved in glycolysis concurs with their transcriptional up-regulation after adipogenic induction, and with downstream elevations in H2BS112GlcNAc levels and O-GlcNAc cycling. 26359231 7 79 from elevations 1437:1446 arg1 cycling 1485:1491 O-GlcNAc cycling 1476:1491 O-GlcNAc cycling 1476:1491 Release of lamin A/C from genes directly involved in glycolysis concurs with their transcriptional up-regulation after adipogenic induction, and with downstream elevations in H2BS112GlcNAc levels and O-GlcNAc cycling. 26359231 8 80 theme sensitive 1669:1677 arg1 modification 1689:1700 a metabolically sensitive chromatin modification 1653:1700 a metabolically sensitive chromatin modification 1653:1700 Our results unveil an epigenetic prepatterning of adipogenic LADs by GADs, suggesting a coupling of developmentally regulated lamin A/C-genome interactions to a metabolically sensitive chromatin modification. 26359231 3 81 from spreading 596:604 arg1 transition 649:658 the transition 645:658 the transition from progenitor cell proliferation to cell-cycle arrest 645:714 We demonstrate a two-step process of lamin A/C LAD formation during in vitro adipogenesis, involving spreading of lamin A/C-chromatin interactions in the transition from progenitor cell proliferation to cell-cycle arrest, and genome-scale redistribution of these interactions through a process of LAD exchange within hours of adipogenic induction. 26359231 0 82 theme nuclear 40:46 arg1 domains 79:85 differentiation-driven nuclear lamin A/C-associated chromatin domains 17:85 differentiation-driven nuclear lamin A/C-associated chromatin domains 17:85 Prepatterning of differentiation-driven nuclear lamin A/C-associated chromatin domains by GlcNAcylated histone H2B. 26359231 3 83 theme cell 676:679 arg1 proliferation 681:693 progenitor cell proliferation 665:693 progenitor cell proliferation 665:693 We demonstrate a two-step process of lamin A/C LAD formation during in vitro adipogenesis, involving spreading of lamin A/C-chromatin interactions in the transition from progenitor cell proliferation to cell-cycle arrest, and genome-scale redistribution of these interactions through a process of LAD exchange within hours of adipogenic induction. 26359231 0 84 theme A/C-associated 54:67 arg1 domains 79:85 differentiation-driven nuclear lamin A/C-associated chromatin domains 17:85 differentiation-driven nuclear lamin A/C-associated chromatin domains 17:85 Prepatterning of differentiation-driven nuclear lamin A/C-associated chromatin domains by GlcNAcylated histone H2B. 26359231 7 85 theme transcriptional 1359:1373 arg1 up-regulation 1375:1387 their transcriptional up-regulation 1353:1387 their transcriptional up-regulation after adipogenic induction 1353:1414 Release of lamin A/C from genes directly involved in glycolysis concurs with their transcriptional up-regulation after adipogenic induction, and with downstream elevations in H2BS112GlcNAc levels and O-GlcNAc cycling. 26359231 2 86 theme sensor 422:427 arg1 H2BS112GlcNAc 459:471 H2BS112GlcNAc 459:471 H2BS112GlcNAc 459:471 Here, we provide evidence for prepatterning of differentiation-driven formation of lamin A/C LADs by domains of histone H2B modified on serine 112 by the nutrient sensor O-linked N-acetylglucosamine (H2BS112GlcNAc), which we term GADs. 26359231 2 86 theme sensor 422:427 arg1 N-acetylglucosamine 438:456 the nutrient sensor O-linked N-acetylglucosamine 409:456 the nutrient sensor O-linked N-acetylglucosamine (H2BS112GlcNAc) 409:472 Here, we provide evidence for prepatterning of differentiation-driven formation of lamin A/C LADs by domains of histone H2B modified on serine 112 by the nutrient sensor O-linked N-acetylglucosamine (H2BS112GlcNAc), which we term GADs. 26359231 0 87 theme domains 79:85 arg1 Prepatterning 0:12 Prepatterning 0:12 Prepatterning of differentiation-driven nuclear lamin A/C-associated chromatin domains by GlcNAcylated histone H2B. 0:114 Prepatterning of differentiation-driven nuclear lamin A/C-associated chromatin domains by GlcNAcylated histone H2B. 26359231 2 88 link O-linked 429:436 arg1 H2BS112GlcNAc 459:471 H2BS112GlcNAc 459:471 H2BS112GlcNAc 459:471 Here, we provide evidence for prepatterning of differentiation-driven formation of lamin A/C LADs by domains of histone H2B modified on serine 112 by the nutrient sensor O-linked N-acetylglucosamine (H2BS112GlcNAc), which we term GADs. 26359231 2 88 link O-linked 429:436 arg1 N-acetylglucosamine 438:456 the nutrient sensor O-linked N-acetylglucosamine 409:456 the nutrient sensor O-linked N-acetylglucosamine (H2BS112GlcNAc) 409:472 Here, we provide evidence for prepatterning of differentiation-driven formation of lamin A/C LADs by domains of histone H2B modified on serine 112 by the nutrient sensor O-linked N-acetylglucosamine (H2BS112GlcNAc), which we term GADs. 26359231 3 89 theme two-step 512:519 arg1 process 521:527 a two-step process 510:527 a two-step process of lamin A/C LAD formation 510:554 We demonstrate a two-step process of lamin A/C LAD formation during in vitro adipogenesis, involving spreading of lamin A/C-chromatin interactions in the transition from progenitor cell proliferation to cell-cycle arrest, and genome-scale redistribution of these interactions through a process of LAD exchange within hours of adipogenic induction. 26359231 6 90 theme A/C 1169:1171 arg1 LADs 1173:1176 predifferentiation lamin A/C LADs 1144:1176 predifferentiation lamin A/C LADs 1144:1176 Accordingly, whereas predifferentiation lamin A/C LADs are gene-rich, post-differentiation LADs harbor repressive features reminiscent of lamin B1 LADs. 26359231 4 91 located found 862:866 arg1 contexts 908:915 active and repressive chromatin contexts 876:915 active and repressive chromatin contexts that can be influenced by cell differentiation status 876:969 Lamin A/C LADs are found both in active and repressive chromatin contexts that can be influenced by cell differentiation status. 26359231 4 91 located found 862:866 arg2 LADs 853:856 Lamin A/C LADs 843:856 Lamin A/C LADs 843:856 Lamin A/C LADs are found both in active and repressive chromatin contexts that can be influenced by cell differentiation status. 26359231 4 92 theme Lamin 843:847 arg1 LADs 853:856 Lamin A/C LADs 843:856 Lamin A/C LADs 843:856 Lamin A/C LADs are found both in active and repressive chromatin contexts that can be influenced by cell differentiation status. 26359231 3 93 theme A/C 538:540 arg1 formation 546:554 lamin A/C LAD formation 532:554 lamin A/C LAD formation 532:554 We demonstrate a two-step process of lamin A/C LAD formation during in vitro adipogenesis, involving spreading of lamin A/C-chromatin interactions in the transition from progenitor cell proliferation to cell-cycle arrest, and genome-scale redistribution of these interactions through a process of LAD exchange within hours of adipogenic induction. 26192747 0 0 from modifications 23:35 arg1 mice 97:100 wild-type and human amyloid precursor protein transgenic mice 40:100 wild-type and human amyloid precursor protein transgenic mice 40:100 Tau post-translational modifications in wild-type and human amyloid precursor protein transgenic mice. 26192747 7 1 theme modification 1022:1033 arg1 hypothesis 958:967 the hypothesis 954:967 the hypothesis of extensive O-linked N-acetylglucosamine (O-GlcNAc) modification of endogenous tau 954:1051 Our findings refute the hypothesis of extensive O-linked N-acetylglucosamine (O-GlcNAc) modification of endogenous tau. 26192747 2 2 theme precursor 384:392 arg1 hAPP 403:406 hAPP 403:406 hAPP 403:406 Reducing tau levels ameliorates AD-related synaptic, network, and behavioral abnormalities in transgenic mice expressing human amyloid precursor protein (hAPP). 26192747 2 2 theme precursor 384:392 arg1 protein 394:400 human amyloid precursor protein 370:400 human amyloid precursor protein (hAPP) 370:407 Reducing tau levels ameliorates AD-related synaptic, network, and behavioral abnormalities in transgenic mice expressing human amyloid precursor protein (hAPP). 26192747 5 3 theme tau 776:778 arg1 forms 767:771 physiological forms 753:771 physiological forms of tau 753:778 Wild-type and hAPP mice had similar modifications, supporting the hypothesis that neuronal dysfunction in hAPP mice is enabled by physiological forms of tau. 26192747 4 4 theme wild-type 607:615 arg1 mice 617:620 wild-type mice 607:620 wild-type mice 607:620 We identified seven types of tau modifications at 63 sites in wild-type mice. 26192747 0 5 theme transgenic 86:95 arg1 mice 97:100 wild-type and human amyloid precursor protein transgenic mice 40:100 wild-type and human amyloid precursor protein transgenic mice 40:100 Tau post-translational modifications in wild-type and human amyloid precursor protein transgenic mice. 26192747 5 6 contain had 647:649 arg2 modifications 659:671 similar modifications 651:671 similar modifications 651:671 Wild-type and hAPP mice had similar modifications, supporting the hypothesis that neuronal dysfunction in hAPP mice is enabled by physiological forms of tau. 26192747 5 6 contain had 647:649 arg1 mice 642:645 Wild-type and hAPP mice 623:645 Wild-type and hAPP mice 623:645 Wild-type and hAPP mice had similar modifications, supporting the hypothesis that neuronal dysfunction in hAPP mice is enabled by physiological forms of tau. 26192747 8 7 theme post-translational 1066:1083 arg1 modification 1085:1096 The complex post-translational modification 1054:1096 The complex post-translational modification of physiological tau 1054:1117 The complex post-translational modification of physiological tau suggests that tau is regulated by diverse mechanisms. 26192747 3 8 attach isolated 506:513 arg2 tau 502:504 endogenous tau 491:504 endogenous tau isolated from wild-type and hAPP mice 491:542 We used mass spectrometry to characterize the post-translational modification of endogenous tau isolated from wild-type and hAPP mice. 26192747 3 8 attach isolated 506:513 arg1 mice 539:542 wild-type and hAPP mice 520:542 wild-type and hAPP mice 520:542 We used mass spectrometry to characterize the post-translational modification of endogenous tau isolated from wild-type and hAPP mice. 26192747 2 9 theme amyloid 376:382 arg1 hAPP 403:406 hAPP 403:406 hAPP 403:406 Reducing tau levels ameliorates AD-related synaptic, network, and behavioral abnormalities in transgenic mice expressing human amyloid precursor protein (hAPP). 26192747 2 9 theme amyloid 376:382 arg1 protein 394:400 human amyloid precursor protein 370:400 human amyloid precursor protein (hAPP) 370:407 Reducing tau levels ameliorates AD-related synaptic, network, and behavioral abnormalities in transgenic mice expressing human amyloid precursor protein (hAPP). 26192747 5 10 theme physiological 753:765 arg1 forms 767:771 physiological forms 753:771 physiological forms of tau 753:778 Wild-type and hAPP mice had similar modifications, supporting the hypothesis that neuronal dysfunction in hAPP mice is enabled by physiological forms of tau. 26192747 8 11 theme physiological 1101:1113 arg1 tau 1115:1117 physiological tau 1101:1117 physiological tau 1101:1117 The complex post-translational modification of physiological tau suggests that tau is regulated by diverse mechanisms. 26192747 7 12 theme O-linked 982:989 arg1 N-acetylglucosamine 991:1009 O-linked N-acetylglucosamine 982:1009 extensive O-linked N-acetylglucosamine (O-GlcNAc) modification of endogenous tau 972:1051 Our findings refute the hypothesis of extensive O-linked N-acetylglucosamine (O-GlcNAc) modification of endogenous tau. 26192747 7 12 theme O-linked 982:989 arg1 O-GlcNAc 1012:1019 O-GlcNAc 1012:1019 O-GlcNAc 1012:1019 Our findings refute the hypothesis of extensive O-linked N-acetylglucosamine (O-GlcNAc) modification of endogenous tau. 26192747 2 13 from abnormalities 326:338 arg1 mice 354:357 transgenic mice 343:357 transgenic mice expressing human amyloid precursor protein (hAPP) 343:407 Reducing tau levels ameliorates AD-related synaptic, network, and behavioral abnormalities in transgenic mice expressing human amyloid precursor protein (hAPP). 26192747 5 14 theme hAPP 637:640 arg1 mice 642:645 Wild-type and hAPP mice 623:645 Wild-type and hAPP mice 623:645 Wild-type and hAPP mice had similar modifications, supporting the hypothesis that neuronal dysfunction in hAPP mice is enabled by physiological forms of tau. 26192747 3 15 theme wild-type 520:528 arg1 mice 539:542 wild-type and hAPP mice 520:542 wild-type and hAPP mice 520:542 We used mass spectrometry to characterize the post-translational modification of endogenous tau isolated from wild-type and hAPP mice. 26192747 6 16 theme lysine 914:919 arg1 methylation 921:931 lysine methylation 914:931 lysine methylation 914:931 Our findings provide clear evidence for acetylation and ubiquitination of the same lysine residues; some sites were also targeted by lysine methylation. 26192747 7 17 theme N-acetylglucosamine 991:1009 arg1 modification 1022:1033 extensive O-linked N-acetylglucosamine (O-GlcNAc) modification 972:1033 extensive O-linked N-acetylglucosamine (O-GlcNAc) modification of endogenous tau 972:1051 Our findings refute the hypothesis of extensive O-linked N-acetylglucosamine (O-GlcNAc) modification of endogenous tau. 26192747 3 18 theme post-translational 456:473 arg1 modification 475:486 the post-translational modification 452:486 the post-translational modification of endogenous tau isolated from wild-type and hAPP mice 452:542 We used mass spectrometry to characterize the post-translational modification of endogenous tau isolated from wild-type and hAPP mice. 26192747 3 19 theme mass 418:421 arg1 spectrometry 423:434 mass spectrometry 418:434 mass spectrometry 418:434 We used mass spectrometry to characterize the post-translational modification of endogenous tau isolated from wild-type and hAPP mice. 26192747 5 20 theme similar 651:657 arg1 modifications 659:671 similar modifications 651:671 similar modifications 651:671 Wild-type and hAPP mice had similar modifications, supporting the hypothesis that neuronal dysfunction in hAPP mice is enabled by physiological forms of tau. 26192747 2 21 theme synaptic 292:299 arg1 network 302:308 network 302:308 network 302:308 Reducing tau levels ameliorates AD-related synaptic, network, and behavioral abnormalities in transgenic mice expressing human amyloid precursor protein (hAPP). 26192747 0 22 theme post-translational 4:21 arg1 modifications 23:35 post-translational modifications 4:35 post-translational modifications in wild-type and human amyloid precursor protein transgenic mice 4:100 Tau post-translational modifications in wild-type and human amyloid precursor protein transgenic mice. 26192747 7 23 theme extensive 972:980 arg1 modification 1022:1033 extensive O-linked N-acetylglucosamine (O-GlcNAc) modification 972:1033 extensive O-linked N-acetylglucosamine (O-GlcNAc) modification of endogenous tau 972:1051 Our findings refute the hypothesis of extensive O-linked N-acetylglucosamine (O-GlcNAc) modification of endogenous tau. 26192747 1 24 theme disease 197:203 arg1 pathogenesis 169:180 the pathogenesis 165:180 the pathogenesis of Alzheimer's disease (AD) and other neurodegenerative disorders 165:246 The microtubule-associated protein tau has been implicated in the pathogenesis of Alzheimer's disease (AD) and other neurodegenerative disorders. 26192747 6 25 theme same 859:862 arg1 residues 871:878 the same lysine residues 855:878 the same lysine residues; some sites were also targeted by lysine methylation 855:931 Our findings provide clear evidence for acetylation and ubiquitination of the same lysine residues; some sites were also targeted by lysine methylation. 26192747 8 26 theme complex 1058:1064 arg1 modification 1085:1096 The complex post-translational modification 1054:1096 The complex post-translational modification of physiological tau 1054:1117 The complex post-translational modification of physiological tau suggests that tau is regulated by diverse mechanisms. 26192747 4 27 theme modifications 578:590 arg1 types 565:569 seven types 559:569 seven types of tau modifications 559:590 We identified seven types of tau modifications at 63 sites in wild-type mice. 26192747 6 28 theme clear 802:806 arg1 evidence 808:815 clear evidence 802:815 clear evidence for acetylation and ubiquitination of the same lysine residues; some sites were also targeted by lysine methylation 802:931 Our findings provide clear evidence for acetylation and ubiquitination of the same lysine residues; some sites were also targeted by lysine methylation. 26192747 2 29 theme behavioral 315:324 arg1 abnormalities 326:338 behavioral abnormalities 315:338 behavioral abnormalities in transgenic mice expressing human amyloid precursor protein (hAPP) 315:407 Reducing tau levels ameliorates AD-related synaptic, network, and behavioral abnormalities in transgenic mice expressing human amyloid precursor protein (hAPP). 26192747 5 30 theme Wild-type 623:631 arg1 mice 642:645 Wild-type and hAPP mice 623:645 Wild-type and hAPP mice 623:645 Wild-type and hAPP mice had similar modifications, supporting the hypothesis that neuronal dysfunction in hAPP mice is enabled by physiological forms of tau. 26192747 3 31 theme tau 502:504 arg1 modification 475:486 the post-translational modification 452:486 the post-translational modification of endogenous tau isolated from wild-type and hAPP mice 452:542 We used mass spectrometry to characterize the post-translational modification of endogenous tau isolated from wild-type and hAPP mice. 26192747 1 32 theme protein 130:136 arg1 tau 138:140 The microtubule-associated protein tau 103:140 The microtubule-associated protein tau 103:140 The microtubule-associated protein tau has been implicated in the pathogenesis of Alzheimer's disease (AD) and other neurodegenerative disorders. 26192747 6 33 dep residues 871:878 arg1 targeted 902:909 targeted 902:909 were also targeted by lysine methylation 892:931 Our findings provide clear evidence for acetylation and ubiquitination of the same lysine residues; some sites were also targeted by lysine methylation. 26192747 8 34 theme diverse 1153:1159 arg1 mechanisms 1161:1170 diverse mechanisms 1153:1170 diverse mechanisms 1153:1170 The complex post-translational modification of physiological tau suggests that tau is regulated by diverse mechanisms. 26192747 0 35 theme wild-type 40:48 arg1 mice 97:100 wild-type and human amyloid precursor protein transgenic mice 40:100 wild-type and human amyloid precursor protein transgenic mice 40:100 Tau post-translational modifications in wild-type and human amyloid precursor protein transgenic mice. 26192747 1 36 theme other 214:218 arg1 disorders 238:246 other neurodegenerative disorders 214:246 other neurodegenerative disorders 214:246 The microtubule-associated protein tau has been implicated in the pathogenesis of Alzheimer's disease (AD) and other neurodegenerative disorders. 26192747 0 37 theme amyloid 60:66 arg1 protein 78:84 human amyloid precursor protein 54:84 human amyloid precursor protein 54:84 Tau post-translational modifications in wild-type and human amyloid precursor protein transgenic mice. 26192747 5 38 theme neuronal 705:712 arg1 dysfunction 714:724 neuronal dysfunction 705:724 neuronal dysfunction in hAPP mice 705:737 Wild-type and hAPP mice had similar modifications, supporting the hypothesis that neuronal dysfunction in hAPP mice is enabled by physiological forms of tau. 26192747 2 39 theme human 370:374 arg1 hAPP 403:406 hAPP 403:406 hAPP 403:406 Reducing tau levels ameliorates AD-related synaptic, network, and behavioral abnormalities in transgenic mice expressing human amyloid precursor protein (hAPP). 26192747 2 39 theme human 370:374 arg1 protein 394:400 human amyloid precursor protein 370:400 human amyloid precursor protein (hAPP) 370:407 Reducing tau levels ameliorates AD-related synaptic, network, and behavioral abnormalities in transgenic mice expressing human amyloid precursor protein (hAPP). 26192747 0 40 theme human 54:58 arg1 protein 78:84 human amyloid precursor protein 54:84 human amyloid precursor protein 54:84 Tau post-translational modifications in wild-type and human amyloid precursor protein transgenic mice. 26192747 4 41 theme tau 574:576 arg1 modifications 578:590 tau modifications 574:590 tau modifications 574:590 We identified seven types of tau modifications at 63 sites in wild-type mice. 26192747 3 42 used used 413:416 arg2 We 410:411 We 410:411 We 410:411 We used mass spectrometry to characterize the post-translational modification of endogenous tau isolated from wild-type and hAPP mice. 26192747 7 43 link O-linked 982:989 arg1 N-acetylglucosamine 991:1009 O-linked N-acetylglucosamine 982:1009 extensive O-linked N-acetylglucosamine (O-GlcNAc) modification of endogenous tau 972:1051 Our findings refute the hypothesis of extensive O-linked N-acetylglucosamine (O-GlcNAc) modification of endogenous tau. 26192747 7 43 link O-linked 982:989 arg1 O-GlcNAc 1012:1019 O-GlcNAc 1012:1019 O-GlcNAc 1012:1019 Our findings refute the hypothesis of extensive O-linked N-acetylglucosamine (O-GlcNAc) modification of endogenous tau. 26192747 8 44 theme tau 1115:1117 arg1 modification 1085:1096 The complex post-translational modification 1054:1096 The complex post-translational modification of physiological tau 1054:1117 The complex post-translational modification of physiological tau suggests that tau is regulated by diverse mechanisms. 26192747 7 45 theme tau 1049:1051 arg1 modification 1022:1033 extensive O-linked N-acetylglucosamine (O-GlcNAc) modification 972:1033 extensive O-linked N-acetylglucosamine (O-GlcNAc) modification of endogenous tau 972:1051 Our findings refute the hypothesis of extensive O-linked N-acetylglucosamine (O-GlcNAc) modification of endogenous tau. 26192747 3 46 theme hAPP 534:537 arg1 mice 539:542 wild-type and hAPP mice 520:542 wild-type and hAPP mice 520:542 We used mass spectrometry to characterize the post-translational modification of endogenous tau isolated from wild-type and hAPP mice. 26192747 6 47 theme residues 871:878 arg1 ubiquitination 837:850 ubiquitination 837:850 ubiquitination 837:850 Our findings provide clear evidence for acetylation and ubiquitination of the same lysine residues; some sites were also targeted by lysine methylation. 26192747 6 47 theme residues 871:878 arg1 acetylation 821:831 acetylation 821:831 acetylation 821:831 Our findings provide clear evidence for acetylation and ubiquitination of the same lysine residues; some sites were also targeted by lysine methylation. 26192747 2 48 theme AD-related 281:290 arg1 network 302:308 network 302:308 network 302:308 Reducing tau levels ameliorates AD-related synaptic, network, and behavioral abnormalities in transgenic mice expressing human amyloid precursor protein (hAPP). 26192747 1 49 theme microtubule-associated 107:128 arg1 tau 138:140 The microtubule-associated protein tau 103:140 The microtubule-associated protein tau 103:140 The microtubule-associated protein tau has been implicated in the pathogenesis of Alzheimer's disease (AD) and other neurodegenerative disorders. 26192747 1 50 theme neurodegenerative 220:236 arg1 disorders 238:246 other neurodegenerative disorders 214:246 other neurodegenerative disorders 214:246 The microtubule-associated protein tau has been implicated in the pathogenesis of Alzheimer's disease (AD) and other neurodegenerative disorders. 26192747 5 51 theme hAPP 729:732 arg1 mice 734:737 hAPP mice 729:737 hAPP mice 729:737 Wild-type and hAPP mice had similar modifications, supporting the hypothesis that neuronal dysfunction in hAPP mice is enabled by physiological forms of tau. 26192747 6 52 theme lysine 864:869 arg1 residues 871:878 the same lysine residues 855:878 the same lysine residues; some sites were also targeted by lysine methylation 855:931 Our findings provide clear evidence for acetylation and ubiquitination of the same lysine residues; some sites were also targeted by lysine methylation. 26192747 2 53 theme transgenic 343:352 arg1 mice 354:357 transgenic mice 343:357 transgenic mice expressing human amyloid precursor protein (hAPP) 343:407 Reducing tau levels ameliorates AD-related synaptic, network, and behavioral abnormalities in transgenic mice expressing human amyloid precursor protein (hAPP). 26192747 1 54 theme disorders 238:246 arg1 pathogenesis 169:180 the pathogenesis 165:180 the pathogenesis of Alzheimer's disease (AD) and other neurodegenerative disorders 165:246 The microtubule-associated protein tau has been implicated in the pathogenesis of Alzheimer's disease (AD) and other neurodegenerative disorders. 26192747 0 55 theme protein 78:84 arg1 mice 97:100 wild-type and human amyloid precursor protein transgenic mice 40:100 wild-type and human amyloid precursor protein transgenic mice 40:100 Tau post-translational modifications in wild-type and human amyloid precursor protein transgenic mice. 26192747 3 56 theme endogenous 491:500 arg1 tau 502:504 endogenous tau 491:504 endogenous tau isolated from wild-type and hAPP mice 491:542 We used mass spectrometry to characterize the post-translational modification of endogenous tau isolated from wild-type and hAPP mice. 26192747 7 57 theme endogenous 1038:1047 arg1 tau 1049:1051 endogenous tau 1038:1051 endogenous tau 1038:1051 Our findings refute the hypothesis of extensive O-linked N-acetylglucosamine (O-GlcNAc) modification of endogenous tau. 26192747 2 58 from network 302:308 arg1 mice 354:357 transgenic mice 343:357 transgenic mice expressing human amyloid precursor protein (hAPP) 343:407 Reducing tau levels ameliorates AD-related synaptic, network, and behavioral abnormalities in transgenic mice expressing human amyloid precursor protein (hAPP). 26192747 0 59 theme precursor 68:76 arg1 protein 78:84 human amyloid precursor protein 54:84 human amyloid precursor protein 54:84 Tau post-translational modifications in wild-type and human amyloid precursor protein transgenic mice. 26192747 7 60 mod modification 1022:1033 arg3 O-GlcNAc 1012:1019 O-GlcNAc 1012:1019 O-GlcNAc 1012:1019 Our findings refute the hypothesis of extensive O-linked N-acetylglucosamine (O-GlcNAc) modification of endogenous tau. 26192747 7 60 mod modification 1022:1033 arg1 tau 1049:1051 endogenous tau 1038:1051 endogenous tau 1038:1051 Our findings refute the hypothesis of extensive O-linked N-acetylglucosamine (O-GlcNAc) modification of endogenous tau. 26192747 7 60 mod modification 1022:1033 arg3 N-acetylglucosamine 991:1009 O-linked N-acetylglucosamine 982:1009 extensive O-linked N-acetylglucosamine (O-GlcNAc) modification of endogenous tau 972:1051 Our findings refute the hypothesis of extensive O-linked N-acetylglucosamine (O-GlcNAc) modification of endogenous tau. 26192747 2 61 theme tau 258:260 arg1 levels 262:267 tau levels 258:267 tau levels 258:267 Reducing tau levels ameliorates AD-related synaptic, network, and behavioral abnormalities in transgenic mice expressing human amyloid precursor protein (hAPP). 26192747 4 62 from sites 598:602 arg1 mice 617:620 wild-type mice 607:620 wild-type mice 607:620 We identified seven types of tau modifications at 63 sites in wild-type mice. 26192747 5 63 from dysfunction 714:724 arg1 mice 734:737 hAPP mice 729:737 hAPP mice 729:737 Wild-type and hAPP mice had similar modifications, supporting the hypothesis that neuronal dysfunction in hAPP mice is enabled by physiological forms of tau. 24416306 1 0 theme JASMONATE-ZIM 134:146 arg1 proteins 171:178 the JASMONATE-ZIM DOMAIN (JAZ) repressor proteins 130:178 the JASMONATE-ZIM DOMAIN (JAZ) repressor proteins 130:178 Jasmonate (JA) signalling is mediated by the JASMONATE-ZIM DOMAIN (JAZ) repressor proteins, which are degraded upon JA perception to release downstream responses. 24416306 9 1 theme deubiquitination 1027:1042 arg1 regulation 994:1003 regulation 994:1003 regulation of dephosphorylation, deubiquitination and O-linked N-acetylglucosamine modification 994:1088 In contrast, TIFY8 was found in protein complexes involved in regulation of dephosphorylation, deubiquitination and O-linked N-acetylglucosamine modification suggesting an important role in nuclear signal transduction. 24416306 0 2 theme transcriptional 62:76 arg1 repressor 78:86 a transcriptional repressor 60:86 a transcriptional repressor 60:86 The non-JAZ TIFY protein TIFY8 from Arabidopsis thaliana is a transcriptional repressor. 24416306 0 2 theme transcriptional 62:76 arg1 TIFY8 25:29 The non-JAZ TIFY protein TIFY8 0:29 The non-JAZ TIFY protein TIFY8 from Arabidopsis thaliana 0:55 The non-JAZ TIFY protein TIFY8 from Arabidopsis thaliana is a transcriptional repressor. 24416306 1 3 theme DOMAIN 148:153 arg1 proteins 171:178 the JASMONATE-ZIM DOMAIN (JAZ) repressor proteins 130:178 the JASMONATE-ZIM DOMAIN (JAZ) repressor proteins 130:178 Jasmonate (JA) signalling is mediated by the JASMONATE-ZIM DOMAIN (JAZ) repressor proteins, which are degraded upon JA perception to release downstream responses. 24416306 4 4 theme functional 453:462 arg1 interaction 477:487 functional and mediated interaction 453:487 functional and mediated interaction with PEAPOD proteins and NINJA 453:518 Here we show that the TIFY8 ZIM domain is functional and mediated interaction with PEAPOD proteins and NINJA. 24416306 4 4 theme functional 453:462 arg1 domain 443:448 the TIFY8 ZIM domain 429:448 the TIFY8 ZIM domain 429:448 Here we show that the TIFY8 ZIM domain is functional and mediated interaction with PEAPOD proteins and NINJA. 24416306 2 5 theme family 320:325 arg1 characteristic 278:291 characteristic 278:291 characteristic of the larger TIFY protein family 278:325 The ZIM protein domain is characteristic of the larger TIFY protein family. 24416306 2 5 theme family 320:325 arg1 domain 268:273 The ZIM protein domain 252:273 The ZIM protein domain 252:273 The ZIM protein domain is characteristic of the larger TIFY protein family. 24416306 9 6 located found 955:959 arg1 complexes 972:980 protein complexes 964:980 protein complexes involved in regulation of dephosphorylation, deubiquitination and O-linked N-acetylglucosamine modification 964:1088 In contrast, TIFY8 was found in protein complexes involved in regulation of dephosphorylation, deubiquitination and O-linked N-acetylglucosamine modification suggesting an important role in nuclear signal transduction. 24416306 9 6 located found 955:959 arg2 TIFY8 945:949 TIFY8 945:949 TIFY8 945:949 In contrast, TIFY8 was found in protein complexes involved in regulation of dephosphorylation, deubiquitination and O-linked N-acetylglucosamine modification suggesting an important role in nuclear signal transduction. 24416306 9 6 located found 955:959 arg1 contrast 935:942 contrast 935:942 contrast 935:942 In contrast, TIFY8 was found in protein complexes involved in regulation of dephosphorylation, deubiquitination and O-linked N-acetylglucosamine modification suggesting an important role in nuclear signal transduction. 24416306 2 7 theme protein 260:266 arg1 characteristic 278:291 characteristic 278:291 characteristic of the larger TIFY protein family 278:325 The ZIM protein domain is characteristic of the larger TIFY protein family. 24416306 2 7 theme protein 260:266 arg1 domain 268:273 The ZIM protein domain 252:273 The ZIM protein domain 252:273 The ZIM protein domain is characteristic of the larger TIFY protein family. 24416306 9 8 theme O-linked 1048:1055 arg1 N-acetylglucosamine 1057:1075 O-linked N-acetylglucosamine 1048:1075 O-linked N-acetylglucosamine modification 1048:1088 In contrast, TIFY8 was found in protein complexes involved in regulation of dephosphorylation, deubiquitination and O-linked N-acetylglucosamine modification suggesting an important role in nuclear signal transduction. 24416306 1 9 theme downstream 230:239 arg1 responses 241:249 downstream responses 230:249 downstream responses 230:249 Jasmonate (JA) signalling is mediated by the JASMONATE-ZIM DOMAIN (JAZ) repressor proteins, which are degraded upon JA perception to release downstream responses. 24416306 0 10 from thaliana 48:55 arg1 repressor 78:86 a transcriptional repressor 60:86 a transcriptional repressor 60:86 The non-JAZ TIFY protein TIFY8 from Arabidopsis thaliana is a transcriptional repressor. 24416306 0 10 from thaliana 48:55 arg1 TIFY8 25:29 The non-JAZ TIFY protein TIFY8 0:29 The non-JAZ TIFY protein TIFY8 from Arabidopsis thaliana 0:55 The non-JAZ TIFY protein TIFY8 from Arabidopsis thaliana is a transcriptional repressor. 24416306 7 11 with lines 772:776 arg1 expression 797:806 altered TIFY8 expression 783:806 altered TIFY8 expression 783:806 Nevertheless, transgenic lines with altered TIFY8 expression did not show changes in JA sensitivity. 24416306 2 12 theme ZIM 256:258 arg1 characteristic 278:291 characteristic 278:291 characteristic of the larger TIFY protein family 278:325 The ZIM protein domain is characteristic of the larger TIFY protein family. 24416306 2 12 theme ZIM 256:258 arg1 domain 268:273 The ZIM protein domain 252:273 The ZIM protein domain 252:273 The ZIM protein domain is characteristic of the larger TIFY protein family. 24416306 8 13 theme functional 860:869 arg1 domain 875:880 the functional ZIM domain 856:880 the functional ZIM domain 856:880 Despite the functional ZIM domain, no interaction with JAZ proteins could be found. 24416306 8 14 theme ZIM 871:873 arg1 domain 875:880 the functional ZIM domain 856:880 the functional ZIM domain 856:880 Despite the functional ZIM domain, no interaction with JAZ proteins could be found. 24416306 9 15 theme N-acetylglucosamine 1057:1075 arg1 modification 1077:1088 O-linked N-acetylglucosamine modification 1048:1088 O-linked N-acetylglucosamine modification 1048:1088 In contrast, TIFY8 was found in protein complexes involved in regulation of dephosphorylation, deubiquitination and O-linked N-acetylglucosamine modification suggesting an important role in nuclear signal transduction. 24416306 9 16 theme modification 1077:1088 arg1 regulation 994:1003 regulation 994:1003 regulation of dephosphorylation, deubiquitination and O-linked N-acetylglucosamine modification 994:1088 In contrast, TIFY8 was found in protein complexes involved in regulation of dephosphorylation, deubiquitination and O-linked N-acetylglucosamine modification suggesting an important role in nuclear signal transduction. 24416306 3 17 theme JA 396:397 arg1 signalling 399:408 JA signalling 396:408 JA signalling 396:408 It is currently unknown if the atypical member TIFY8 is involved in JA signalling. 24416306 6 18 with infection 710:718 arg1 syringae 737:744 Pseudomonas syringae 725:744 Pseudomonas syringae 725:744 TIFY8 expression was inversely correlated with JAZ expression during development and after infection with Pseudomonas syringae. 24416306 4 19 theme ZIM 439:441 arg1 interaction 477:487 functional and mediated interaction 453:487 functional and mediated interaction with PEAPOD proteins and NINJA 453:518 Here we show that the TIFY8 ZIM domain is functional and mediated interaction with PEAPOD proteins and NINJA. 24416306 4 19 theme ZIM 439:441 arg1 domain 443:448 the TIFY8 ZIM domain 429:448 the TIFY8 ZIM domain 429:448 Here we show that the TIFY8 ZIM domain is functional and mediated interaction with PEAPOD proteins and NINJA. 24416306 8 20 with interaction 886:896 arg1 proteins 907:914 JAZ proteins 903:914 JAZ proteins 903:914 Despite the functional ZIM domain, no interaction with JAZ proteins could be found. 24416306 7 21 theme JA 832:833 arg1 sensitivity 835:845 JA sensitivity 832:845 JA sensitivity 832:845 Nevertheless, transgenic lines with altered TIFY8 expression did not show changes in JA sensitivity. 24416306 1 22 theme JAZ 156:158 arg1 proteins 171:178 the JASMONATE-ZIM DOMAIN (JAZ) repressor proteins 130:178 the JASMONATE-ZIM DOMAIN (JAZ) repressor proteins 130:178 Jasmonate (JA) signalling is mediated by the JASMONATE-ZIM DOMAIN (JAZ) repressor proteins, which are degraded upon JA perception to release downstream responses. 24416306 0 23 theme non-JAZ 4:10 arg1 repressor 78:86 a transcriptional repressor 60:86 a transcriptional repressor 60:86 The non-JAZ TIFY protein TIFY8 from Arabidopsis thaliana is a transcriptional repressor. 24416306 0 23 theme non-JAZ 4:10 arg1 TIFY8 25:29 The non-JAZ TIFY protein TIFY8 0:29 The non-JAZ TIFY protein TIFY8 from Arabidopsis thaliana 0:55 The non-JAZ TIFY protein TIFY8 from Arabidopsis thaliana is a transcriptional repressor. 24416306 4 24 theme TIFY8 433:437 arg1 interaction 477:487 functional and mediated interaction 453:487 functional and mediated interaction with PEAPOD proteins and NINJA 453:518 Here we show that the TIFY8 ZIM domain is functional and mediated interaction with PEAPOD proteins and NINJA. 24416306 4 24 theme TIFY8 433:437 arg1 domain 443:448 the TIFY8 ZIM domain 429:448 the TIFY8 ZIM domain 429:448 Here we show that the TIFY8 ZIM domain is functional and mediated interaction with PEAPOD proteins and NINJA. 24416306 6 25 theme JAZ 666:668 arg1 expression 670:679 JAZ expression 666:679 JAZ expression during development and after infection with Pseudomonas syringae 666:744 TIFY8 expression was inversely correlated with JAZ expression during development and after infection with Pseudomonas syringae. 24416306 5 26 theme transcriptional 592:606 arg1 TIFY8 521:525 TIFY8 521:525 TIFY8 521:525 TIFY8 interacted with TOPLESS through NINJA and accordingly acted as a transcriptional repressor. 24416306 5 26 theme transcriptional 592:606 arg1 repressor 608:616 a transcriptional repressor 590:616 a transcriptional repressor 590:616 TIFY8 interacted with TOPLESS through NINJA and accordingly acted as a transcriptional repressor. 24416306 1 27 theme Jasmonate 89:97 arg1 signalling 104:113 Jasmonate (JA) signalling 89:113 Jasmonate (JA) signalling 89:113 Jasmonate (JA) signalling is mediated by the JASMONATE-ZIM DOMAIN (JAZ) repressor proteins, which are degraded upon JA perception to release downstream responses. 24416306 9 28 theme important 1104:1112 arg1 role 1114:1117 an important role 1101:1117 an important role in nuclear signal transduction 1101:1148 In contrast, TIFY8 was found in protein complexes involved in regulation of dephosphorylation, deubiquitination and O-linked N-acetylglucosamine modification suggesting an important role in nuclear signal transduction. 24416306 1 29 theme repressor 161:169 arg1 proteins 171:178 the JASMONATE-ZIM DOMAIN (JAZ) repressor proteins 130:178 the JASMONATE-ZIM DOMAIN (JAZ) repressor proteins 130:178 Jasmonate (JA) signalling is mediated by the JASMONATE-ZIM DOMAIN (JAZ) repressor proteins, which are degraded upon JA perception to release downstream responses. 24416306 0 30 theme protein 17:23 arg1 repressor 78:86 a transcriptional repressor 60:86 a transcriptional repressor 60:86 The non-JAZ TIFY protein TIFY8 from Arabidopsis thaliana is a transcriptional repressor. 24416306 0 30 theme protein 17:23 arg1 TIFY8 25:29 The non-JAZ TIFY protein TIFY8 0:29 The non-JAZ TIFY protein TIFY8 from Arabidopsis thaliana 0:55 The non-JAZ TIFY protein TIFY8 from Arabidopsis thaliana is a transcriptional repressor. 24416306 4 31 with interaction 477:487 arg1 NINJA 514:518 NINJA 514:518 NINJA 514:518 Here we show that the TIFY8 ZIM domain is functional and mediated interaction with PEAPOD proteins and NINJA. 24416306 4 31 with interaction 477:487 arg1 proteins 501:508 PEAPOD proteins 494:508 PEAPOD proteins 494:508 Here we show that the TIFY8 ZIM domain is functional and mediated interaction with PEAPOD proteins and NINJA. 24416306 0 32 theme TIFY 12:15 arg1 repressor 78:86 a transcriptional repressor 60:86 a transcriptional repressor 60:86 The non-JAZ TIFY protein TIFY8 from Arabidopsis thaliana is a transcriptional repressor. 24416306 0 32 theme TIFY 12:15 arg1 TIFY8 25:29 The non-JAZ TIFY protein TIFY8 0:29 The non-JAZ TIFY protein TIFY8 from Arabidopsis thaliana 0:55 The non-JAZ TIFY protein TIFY8 from Arabidopsis thaliana is a transcriptional repressor. 24416306 7 33 theme altered 783:789 arg1 expression 797:806 altered TIFY8 expression 783:806 altered TIFY8 expression 783:806 Nevertheless, transgenic lines with altered TIFY8 expression did not show changes in JA sensitivity. 24416306 1 34 theme JA 100:101 arg1 signalling 104:113 Jasmonate (JA) signalling 89:113 Jasmonate (JA) signalling 89:113 Jasmonate (JA) signalling is mediated by the JASMONATE-ZIM DOMAIN (JAZ) repressor proteins, which are degraded upon JA perception to release downstream responses. 24416306 7 35 theme TIFY8 791:795 arg1 expression 797:806 altered TIFY8 expression 783:806 altered TIFY8 expression 783:806 Nevertheless, transgenic lines with altered TIFY8 expression did not show changes in JA sensitivity. 24416306 9 36 link O-linked 1048:1055 arg1 N-acetylglucosamine 1057:1075 O-linked N-acetylglucosamine 1048:1075 O-linked N-acetylglucosamine modification 1048:1088 In contrast, TIFY8 was found in protein complexes involved in regulation of dephosphorylation, deubiquitination and O-linked N-acetylglucosamine modification suggesting an important role in nuclear signal transduction. 24416306 9 37 theme nuclear 1122:1128 arg1 transduction 1137:1148 nuclear signal transduction 1122:1148 nuclear signal transduction 1122:1148 In contrast, TIFY8 was found in protein complexes involved in regulation of dephosphorylation, deubiquitination and O-linked N-acetylglucosamine modification suggesting an important role in nuclear signal transduction. 24416306 9 38 theme protein 964:970 arg1 complexes 972:980 protein complexes 964:980 protein complexes involved in regulation of dephosphorylation, deubiquitination and O-linked N-acetylglucosamine modification 964:1088 In contrast, TIFY8 was found in protein complexes involved in regulation of dephosphorylation, deubiquitination and O-linked N-acetylglucosamine modification suggesting an important role in nuclear signal transduction. 24416306 9 39 theme signal 1130:1135 arg1 transduction 1137:1148 nuclear signal transduction 1122:1148 nuclear signal transduction 1122:1148 In contrast, TIFY8 was found in protein complexes involved in regulation of dephosphorylation, deubiquitination and O-linked N-acetylglucosamine modification suggesting an important role in nuclear signal transduction. 24416306 3 40 theme atypical 359:366 arg1 member 368:373 the atypical member 355:373 the atypical member TIFY8 is involved in JA signalling 355:408 It is currently unknown if the atypical member TIFY8 is involved in JA signalling. 24416306 4 41 theme mediated 468:475 arg1 interaction 477:487 functional and mediated interaction 453:487 functional and mediated interaction with PEAPOD proteins and NINJA 453:518 Here we show that the TIFY8 ZIM domain is functional and mediated interaction with PEAPOD proteins and NINJA. 24416306 4 41 theme mediated 468:475 arg1 domain 443:448 the TIFY8 ZIM domain 429:448 the TIFY8 ZIM domain 429:448 Here we show that the TIFY8 ZIM domain is functional and mediated interaction with PEAPOD proteins and NINJA. 24416306 7 42 from changes 821:827 arg1 sensitivity 835:845 JA sensitivity 832:845 JA sensitivity 832:845 Nevertheless, transgenic lines with altered TIFY8 expression did not show changes in JA sensitivity. 24416306 8 43 theme JAZ 903:905 arg1 proteins 907:914 JAZ proteins 903:914 JAZ proteins 903:914 Despite the functional ZIM domain, no interaction with JAZ proteins could be found. 24416306 2 44 theme protein 312:318 arg1 family 320:325 the larger TIFY protein family 296:325 the larger TIFY protein family 296:325 The ZIM protein domain is characteristic of the larger TIFY protein family. 24416306 0 45 theme Arabidopsis 36:46 arg1 thaliana 48:55 Arabidopsis thaliana 36:55 Arabidopsis thaliana 36:55 The non-JAZ TIFY protein TIFY8 from Arabidopsis thaliana is a transcriptional repressor. 24416306 4 46 theme PEAPOD 494:499 arg1 proteins 501:508 PEAPOD proteins 494:508 PEAPOD proteins 494:508 Here we show that the TIFY8 ZIM domain is functional and mediated interaction with PEAPOD proteins and NINJA. 24416306 9 47 from role 1114:1117 arg1 transduction 1137:1148 nuclear signal transduction 1122:1148 nuclear signal transduction 1122:1148 In contrast, TIFY8 was found in protein complexes involved in regulation of dephosphorylation, deubiquitination and O-linked N-acetylglucosamine modification suggesting an important role in nuclear signal transduction. 24416306 2 48 theme TIFY 307:310 arg1 family 320:325 the larger TIFY protein family 296:325 the larger TIFY protein family 296:325 The ZIM protein domain is characteristic of the larger TIFY protein family. 24416306 7 49 theme transgenic 761:770 arg1 lines 772:776 transgenic lines 761:776 transgenic lines with altered TIFY8 expression 761:806 Nevertheless, transgenic lines with altered TIFY8 expression did not show changes in JA sensitivity. 24416306 2 50 theme larger 300:305 arg1 family 320:325 the larger TIFY protein family 296:325 the larger TIFY protein family 296:325 The ZIM protein domain is characteristic of the larger TIFY protein family. 24416306 6 51 theme TIFY8 619:623 arg1 expression 625:634 TIFY8 expression 619:634 TIFY8 expression 619:634 TIFY8 expression was inversely correlated with JAZ expression during development and after infection with Pseudomonas syringae. 24416306 9 52 theme dephosphorylation 1008:1024 arg1 regulation 994:1003 regulation 994:1003 regulation of dephosphorylation, deubiquitination and O-linked N-acetylglucosamine modification 994:1088 In contrast, TIFY8 was found in protein complexes involved in regulation of dephosphorylation, deubiquitination and O-linked N-acetylglucosamine modification suggesting an important role in nuclear signal transduction. 24416306 1 53 theme JA 205:206 arg1 perception 208:217 JA perception 205:217 JA perception 205:217 Jasmonate (JA) signalling is mediated by the JASMONATE-ZIM DOMAIN (JAZ) repressor proteins, which are degraded upon JA perception to release downstream responses. 26584015 0 0 theme Male 101:104 arg1 Rats 106:109 Male Rats 101:109 Male Rats With Testosterone-Deficient Metabolic Syndrome 101:156 Trenbolone Improves Cardiometabolic Risk Factors and Myocardial Tolerance to Ischemia-Reperfusion in Male Rats With Testosterone-Deficient Metabolic Syndrome. 26584015 8 1 theme myocardial 1196:1205 arg1 damage 1207:1212 myocardial damage 1196:1212 myocardial damage 1196:1212 The HF/HS+ORX animals had increased sc and visceral adiposity; circulating triglycerides, cholesterol, and insulin; and myocardial damage, with low circulating TEST compared with CTRLs. 26584015 4 2 theme feeding 660:666 arg1 weeks 651:655 8 weeks 649:655 8 weeks of feeding 649:666 After 8 weeks of feeding, rats underwent sham surgery or an orchiectomy (ORX). 26584015 7 3 theme Infarct 930:936 arg1 size 938:941 Infarct size 930:941 Infarct size 930:941 Infarct size was quantified to assess myocardial damage after in vivo ischaemia reperfusion, before cardiac and prostate histology was performed. 26584015 1 4 theme obesity 188:194 arg1 prevalence 174:183 The increasing prevalence 159:183 The increasing prevalence of obesity 159:194 The increasing prevalence of obesity adds another dimension to the pathophysiology of testosterone (TEST) deficiency (TD) and potentially impairs the therapeutic efficacy of classical TEST replacement therapy. 26584015 10 5 theme myocardial 1505:1514 arg1 damage 1516:1521 myocardial damage 1505:1521 myocardial damage 1505:1521 However, only TREN protected against visceral fat accumulation, hypertriglyceridaemia, and hyperinsulinaemia and reduced myocardial damage relative to CTRLs. 26584015 9 6 theme myocardial 1365:1374 arg1 damage 1376:1381 myocardial damage 1365:1381 myocardial damage 1365:1381 Both TEST and TREN protected HF/HS+ORX animals against sc fat accumulation, hypercholesterolaemia, and myocardial damage. 26584015 2 7 theme metabolic 500:508 arg1 MetS 520:523 MetS 520:523 MetS 520:523 We investigated the therapeutic effects of selective androgen receptor modulation with trenbolone (TREN) in a model of TD with the metabolic syndrome (MetS). 26584015 2 7 theme metabolic 500:508 arg1 syndrome 510:517 the metabolic syndrome 496:517 the metabolic syndrome (MetS) 496:524 We investigated the therapeutic effects of selective androgen receptor modulation with trenbolone (TREN) in a model of TD with the metabolic syndrome (MetS). 26584015 2 8 with modulation 440:449 arg1 trenbolone 456:465 trenbolone 456:465 trenbolone (TREN) 456:472 We investigated the therapeutic effects of selective androgen receptor modulation with trenbolone (TREN) in a model of TD with the metabolic syndrome (MetS). 26584015 2 8 with modulation 440:449 arg1 TREN 468:471 TREN 468:471 TREN 468:471 We investigated the therapeutic effects of selective androgen receptor modulation with trenbolone (TREN) in a model of TD with the metabolic syndrome (MetS). 26584015 10 9 theme only 1393:1396 arg1 TREN 1398:1401 only TREN 1393:1401 only TREN 1393:1401 However, only TREN protected against visceral fat accumulation, hypertriglyceridaemia, and hyperinsulinaemia and reduced myocardial damage relative to CTRLs. 26584015 12 10 with males 1718:1722 arg1 MetS 1752:1755 TD and obesity-related MetS 1729:1755 TD and obesity-related MetS 1729:1755 We propose that TEST replacement therapy may have contraindications for males with TD and obesity-related MetS. 26584015 11 11 theme prostate 1586:1593 arg1 hyperplasia 1595:1605 prostate hyperplasia 1586:1605 prostate hyperplasia 1586:1605 TEST caused widespread cardiac fibrosis and prostate hyperplasia, which were less pronounced with TREN. 26584015 2 12 theme therapeutic 389:399 arg1 effects 401:407 the therapeutic effects 385:407 the therapeutic effects of selective androgen receptor modulation with trenbolone (TREN) in a model of TD with the metabolic syndrome (MetS) 385:524 We investigated the therapeutic effects of selective androgen receptor modulation with trenbolone (TREN) in a model of TD with the metabolic syndrome (MetS). 26584015 8 13 theme HF/HS+ORX 1080:1088 arg1 animals 1090:1096 The HF/HS+ORX animals 1076:1096 The HF/HS+ORX animals 1076:1096 The HF/HS+ORX animals had increased sc and visceral adiposity; circulating triglycerides, cholesterol, and insulin; and myocardial damage, with low circulating TEST compared with CTRLs. 26584015 0 14 theme Metabolic 139:147 arg1 Syndrome 149:156 Testosterone-Deficient Metabolic Syndrome 116:156 Testosterone-Deficient Metabolic Syndrome 116:156 Trenbolone Improves Cardiometabolic Risk Factors and Myocardial Tolerance to Ischemia-Reperfusion in Male Rats With Testosterone-Deficient Metabolic Syndrome. 26584015 6 15 theme Body 840:843 arg1 composition 845:855 Body composition 840:855 Body composition 840:855 Body composition, fat distribution, lipid profile, and insulin sensitivity were assessed. 26584015 7 16 theme prostate 1042:1049 arg1 histology 1051:1059 prostate histology 1042:1059 prostate histology 1042:1059 Infarct size was quantified to assess myocardial damage after in vivo ischaemia reperfusion, before cardiac and prostate histology was performed. 26584015 11 17 with pronounced 1624:1633 arg1 TREN 1640:1643 TREN 1640:1643 TREN 1640:1643 TEST caused widespread cardiac fibrosis and prostate hyperplasia, which were less pronounced with TREN. 26584015 2 18 theme modulation 440:449 arg1 effects 401:407 the therapeutic effects 385:407 the therapeutic effects of selective androgen receptor modulation with trenbolone (TREN) in a model of TD with the metabolic syndrome (MetS) 385:524 We investigated the therapeutic effects of selective androgen receptor modulation with trenbolone (TREN) in a model of TD with the metabolic syndrome (MetS). 26584015 0 19 theme Testosterone-Deficient 116:137 arg1 Syndrome 149:156 Testosterone-Deficient Metabolic Syndrome 116:156 Testosterone-Deficient Metabolic Syndrome 116:156 Trenbolone Improves Cardiometabolic Risk Factors and Myocardial Tolerance to Ischemia-Reperfusion in Male Rats With Testosterone-Deficient Metabolic Syndrome. 26584015 10 20 theme fat 1430:1432 arg1 accumulation 1434:1445 visceral fat accumulation 1421:1445 visceral fat accumulation 1421:1445 However, only TREN protected against visceral fat accumulation, hypertriglyceridaemia, and hyperinsulinaemia and reduced myocardial damage relative to CTRLs. 26584015 12 21 theme TD 1729:1730 arg1 MetS 1752:1755 TD and obesity-related MetS 1729:1755 TD and obesity-related MetS 1729:1755 We propose that TEST replacement therapy may have contraindications for males with TD and obesity-related MetS. 26584015 2 22 theme receptor 431:438 arg1 modulation 440:449 selective androgen receptor modulation 412:449 selective androgen receptor modulation with trenbolone (TREN) 412:472 We investigated the therapeutic effects of selective androgen receptor modulation with trenbolone (TREN) in a model of TD with the metabolic syndrome (MetS). 26584015 8 23 theme circulating 1139:1149 arg1 triglycerides 1151:1163 triglycerides 1151:1163 triglycerides 1151:1163 The HF/HS+ORX animals had increased sc and visceral adiposity; circulating triglycerides, cholesterol, and insulin; and myocardial damage, with low circulating TEST compared with CTRLs. 26584015 10 24 theme visceral 1421:1428 arg1 accumulation 1434:1445 visceral fat accumulation 1421:1445 visceral fat accumulation 1421:1445 However, only TREN protected against visceral fat accumulation, hypertriglyceridaemia, and hyperinsulinaemia and reduced myocardial damage relative to CTRLs. 26584015 11 25 theme widespread 1554:1563 arg1 fibrosis 1573:1580 widespread cardiac fibrosis 1554:1580 widespread cardiac fibrosis 1554:1580 TEST caused widespread cardiac fibrosis and prostate hyperplasia, which were less pronounced with TREN. 26584015 13 26 theme androgen 1808:1815 arg1 status 1817:1822 androgen status 1808:1822 androgen status 1808:1822 TREN treatment may be more effective in restoring androgen status and reducing cardiovascular risk in males with TD and MetS. 26584015 2 27 theme androgen 422:429 arg1 modulation 440:449 selective androgen receptor modulation 412:449 selective androgen receptor modulation with trenbolone (TREN) 412:472 We investigated the therapeutic effects of selective androgen receptor modulation with trenbolone (TREN) in a model of TD with the metabolic syndrome (MetS). 26584015 6 28 theme fat 858:860 arg1 distribution 862:873 fat distribution 858:873 fat distribution 858:873 Body composition, fat distribution, lipid profile, and insulin sensitivity were assessed. 26584015 13 29 with males 1860:1864 arg1 MetS 1878:1881 MetS 1878:1881 MetS 1878:1881 TREN treatment may be more effective in restoring androgen status and reducing cardiovascular risk in males with TD and MetS. 26584015 13 29 with males 1860:1864 arg1 TD 1871:1872 TD 1871:1872 TD 1871:1872 TREN treatment may be more effective in restoring androgen status and reducing cardiovascular risk in males with TD and MetS. 26584015 9 30 theme fat 1320:1322 arg1 accumulation 1324:1335 sc fat accumulation 1317:1335 sc fat accumulation 1317:1335 Both TEST and TREN protected HF/HS+ORX animals against sc fat accumulation, hypercholesterolaemia, and myocardial damage. 26584015 2 31 theme selective 412:420 arg1 modulation 440:449 selective androgen receptor modulation 412:449 selective androgen receptor modulation with trenbolone (TREN) 412:472 We investigated the therapeutic effects of selective androgen receptor modulation with trenbolone (TREN) in a model of TD with the metabolic syndrome (MetS). 26584015 0 32 theme Risk 36:39 arg1 Factors 41:47 Cardiometabolic Risk Factors 20:47 Cardiometabolic Risk Factors 20:47 Trenbolone Improves Cardiometabolic Risk Factors and Myocardial Tolerance to Ischemia-Reperfusion in Male Rats With Testosterone-Deficient Metabolic Syndrome. 26584015 8 33 theme visceral 1119:1126 arg1 adiposity 1128:1136 visceral adiposity 1119:1136 visceral adiposity 1119:1136 The HF/HS+ORX animals had increased sc and visceral adiposity; circulating triglycerides, cholesterol, and insulin; and myocardial damage, with low circulating TEST compared with CTRLs. 26584015 0 34 with Rats 106:109 arg1 Syndrome 149:156 Testosterone-Deficient Metabolic Syndrome 116:156 Testosterone-Deficient Metabolic Syndrome 116:156 Trenbolone Improves Cardiometabolic Risk Factors and Myocardial Tolerance to Ischemia-Reperfusion in Male Rats With Testosterone-Deficient Metabolic Syndrome. 26584015 0 35 theme Cardiometabolic 20:34 arg1 Factors 41:47 Cardiometabolic Risk Factors 20:47 Cardiometabolic Risk Factors 20:47 Trenbolone Improves Cardiometabolic Risk Factors and Myocardial Tolerance to Ischemia-Reperfusion in Male Rats With Testosterone-Deficient Metabolic Syndrome. 26584015 1 36 theme therapeutic 309:319 arg1 efficacy 321:328 the therapeutic efficacy 305:328 the therapeutic efficacy of classical TEST replacement therapy 305:366 The increasing prevalence of obesity adds another dimension to the pathophysiology of testosterone (TEST) deficiency (TD) and potentially impairs the therapeutic efficacy of classical TEST replacement therapy. 26584015 13 37 theme cardiovascular 1837:1850 arg1 risk 1852:1855 cardiovascular risk 1837:1855 cardiovascular risk in males with TD and MetS 1837:1881 TREN treatment may be more effective in restoring androgen status and reducing cardiovascular risk in males with TD and MetS. 26584015 5 38 theme Alzet 722:726 arg1 pumps 740:744 Alzet miniosmotic pumps 722:744 Alzet miniosmotic pumps containing either vehicle, 2-mg/kg·d TEST or 2-mg/kg·d TREN 722:804 Alzet miniosmotic pumps containing either vehicle, 2-mg/kg·d TEST or 2-mg/kg·d TREN were implanted in HF/HS+ORX rats. 26584015 6 39 theme insulin 895:901 arg1 sensitivity 903:913 insulin sensitivity 895:913 insulin sensitivity 895:913 Body composition, fat distribution, lipid profile, and insulin sensitivity were assessed. 26584015 13 40 theme TREN 1758:1761 arg1 treatment 1763:1771 TREN treatment 1758:1771 TREN treatment 1758:1771 TREN treatment may be more effective in restoring androgen status and reducing cardiovascular risk in males with TD and MetS. 26584015 5 41 theme 2-mg/kg·d 791:799 arg1 TREN 801:804 2-mg/kg·d TREN 791:804 2-mg/kg·d TREN 791:804 Alzet miniosmotic pumps containing either vehicle, 2-mg/kg·d TEST or 2-mg/kg·d TREN were implanted in HF/HS+ORX rats. 26584015 3 42 theme rat 586:588 arg1 CTRL 596:599 CTRL 596:599 CTRL 596:599 Male Wistar rats (n=50) were fed either a control standard rat chow (CTRL) or a high-fat/high-sucrose (HF/HS) diet. 26584015 3 42 theme rat 586:588 arg1 chow 590:593 a control standard rat chow 567:593 a control standard rat chow (CTRL) 567:600 Male Wistar rats (n=50) were fed either a control standard rat chow (CTRL) or a high-fat/high-sucrose (HF/HS) diet. 26584015 5 43 theme HF/HS+ORX 824:832 arg1 rats 834:837 HF/HS+ORX rats 824:837 HF/HS+ORX rats 824:837 Alzet miniosmotic pumps containing either vehicle, 2-mg/kg·d TEST or 2-mg/kg·d TREN were implanted in HF/HS+ORX rats. 26584015 1 44 theme testosterone 245:256 arg1 deficiency 265:274 testosterone (TEST) deficiency 245:274 testosterone (TEST) deficiency (TD) 245:279 The increasing prevalence of obesity adds another dimension to the pathophysiology of testosterone (TEST) deficiency (TD) and potentially impairs the therapeutic efficacy of classical TEST replacement therapy. 26584015 1 44 theme testosterone 245:256 arg1 TD 277:278 TD 277:278 TD 277:278 The increasing prevalence of obesity adds another dimension to the pathophysiology of testosterone (TEST) deficiency (TD) and potentially impairs the therapeutic efficacy of classical TEST replacement therapy. 26584015 5 45 theme miniosmotic 728:738 arg1 pumps 740:744 Alzet miniosmotic pumps 722:744 Alzet miniosmotic pumps containing either vehicle, 2-mg/kg·d TEST or 2-mg/kg·d TREN 722:804 Alzet miniosmotic pumps containing either vehicle, 2-mg/kg·d TEST or 2-mg/kg·d TREN were implanted in HF/HS+ORX rats. 26584015 8 46 theme circulating 1224:1234 arg1 TEST 1236:1239 low circulating TEST 1220:1239 low circulating TEST 1220:1239 The HF/HS+ORX animals had increased sc and visceral adiposity; circulating triglycerides, cholesterol, and insulin; and myocardial damage, with low circulating TEST compared with CTRLs. 26584015 2 47 from effects 401:407 arg1 model 479:483 a model 477:483 a model of TD with the metabolic syndrome (MetS) 477:524 We investigated the therapeutic effects of selective androgen receptor modulation with trenbolone (TREN) in a model of TD with the metabolic syndrome (MetS). 26584015 6 48 theme lipid 876:880 arg1 profile 882:888 lipid profile 876:888 lipid profile 876:888 Body composition, fat distribution, lipid profile, and insulin sensitivity were assessed. 26584015 2 49 theme TD 488:489 arg1 model 479:483 a model 477:483 a model of TD with the metabolic syndrome (MetS) 477:524 We investigated the therapeutic effects of selective androgen receptor modulation with trenbolone (TREN) in a model of TD with the metabolic syndrome (MetS). 26584015 1 50 theme classical 333:341 arg1 therapy 360:366 classical TEST replacement therapy 333:366 classical TEST replacement therapy 333:366 The increasing prevalence of obesity adds another dimension to the pathophysiology of testosterone (TEST) deficiency (TD) and potentially impairs the therapeutic efficacy of classical TEST replacement therapy. 26584015 7 51 theme in 992:993 arg1 ischaemia 1000:1008 in vivo ischaemia 992:1008 in vivo ischaemia reperfusion 992:1020 Infarct size was quantified to assess myocardial damage after in vivo ischaemia reperfusion, before cardiac and prostate histology was performed. 26584015 3 52 theme high-fat/high-sucrose 607:627 arg1 diet 637:640 a high-fat/high-sucrose (HF/HS) diet 605:640 a high-fat/high-sucrose (HF/HS) diet 605:640 Male Wistar rats (n=50) were fed either a control standard rat chow (CTRL) or a high-fat/high-sucrose (HF/HS) diet. 26584015 3 52 theme high-fat/high-sucrose 607:627 arg1 HF/HS 630:634 HF/HS 630:634 HF/HS 630:634 Male Wistar rats (n=50) were fed either a control standard rat chow (CTRL) or a high-fat/high-sucrose (HF/HS) diet. 26584015 3 53 theme control 569:575 arg1 CTRL 596:599 CTRL 596:599 CTRL 596:599 Male Wistar rats (n=50) were fed either a control standard rat chow (CTRL) or a high-fat/high-sucrose (HF/HS) diet. 26584015 3 53 theme control 569:575 arg1 chow 590:593 a control standard rat chow 567:593 a control standard rat chow (CTRL) 567:600 Male Wistar rats (n=50) were fed either a control standard rat chow (CTRL) or a high-fat/high-sucrose (HF/HS) diet. 26584015 7 54 theme myocardial 968:977 arg1 damage 979:984 myocardial damage 968:984 myocardial damage 968:984 Infarct size was quantified to assess myocardial damage after in vivo ischaemia reperfusion, before cardiac and prostate histology was performed. 26584015 0 55 theme Myocardial 53:62 arg1 Tolerance 64:72 Myocardial Tolerance 53:72 Myocardial Tolerance to Ischemia-Reperfusion 53:96 Trenbolone Improves Cardiometabolic Risk Factors and Myocardial Tolerance to Ischemia-Reperfusion in Male Rats With Testosterone-Deficient Metabolic Syndrome. 26584015 1 56 theme TEST 343:346 arg1 therapy 360:366 classical TEST replacement therapy 333:366 classical TEST replacement therapy 333:366 The increasing prevalence of obesity adds another dimension to the pathophysiology of testosterone (TEST) deficiency (TD) and potentially impairs the therapeutic efficacy of classical TEST replacement therapy. 26584015 5 57 contain containing 746:755 arg1 pumps 740:744 Alzet miniosmotic pumps 722:744 Alzet miniosmotic pumps containing either vehicle, 2-mg/kg·d TEST or 2-mg/kg·d TREN 722:804 Alzet miniosmotic pumps containing either vehicle, 2-mg/kg·d TEST or 2-mg/kg·d TREN were implanted in HF/HS+ORX rats. 26584015 5 57 contain containing 746:755 arg2 TEST 783:786 2-mg/kg·d TEST 773:786 2-mg/kg·d TEST 773:786 Alzet miniosmotic pumps containing either vehicle, 2-mg/kg·d TEST or 2-mg/kg·d TREN were implanted in HF/HS+ORX rats. 26584015 5 57 contain containing 746:755 arg2 vehicle 764:770 vehicle 764:770 vehicle 764:770 Alzet miniosmotic pumps containing either vehicle, 2-mg/kg·d TEST or 2-mg/kg·d TREN were implanted in HF/HS+ORX rats. 26584015 5 57 contain containing 746:755 arg2 TREN 801:804 2-mg/kg·d TREN 791:804 2-mg/kg·d TREN 791:804 Alzet miniosmotic pumps containing either vehicle, 2-mg/kg·d TEST or 2-mg/kg·d TREN were implanted in HF/HS+ORX rats. 26584015 3 58 theme standard 577:584 arg1 CTRL 596:599 CTRL 596:599 CTRL 596:599 Male Wistar rats (n=50) were fed either a control standard rat chow (CTRL) or a high-fat/high-sucrose (HF/HS) diet. 26584015 3 58 theme standard 577:584 arg1 chow 590:593 a control standard rat chow 567:593 a control standard rat chow (CTRL) 567:600 Male Wistar rats (n=50) were fed either a control standard rat chow (CTRL) or a high-fat/high-sucrose (HF/HS) diet. 26584015 11 59 theme cardiac 1565:1571 arg1 fibrosis 1573:1580 widespread cardiac fibrosis 1554:1580 widespread cardiac fibrosis 1554:1580 TEST caused widespread cardiac fibrosis and prostate hyperplasia, which were less pronounced with TREN. 26584015 1 60 theme replacement 348:358 arg1 therapy 360:366 classical TEST replacement therapy 333:366 classical TEST replacement therapy 333:366 The increasing prevalence of obesity adds another dimension to the pathophysiology of testosterone (TEST) deficiency (TD) and potentially impairs the therapeutic efficacy of classical TEST replacement therapy. 26584015 13 61 from risk 1852:1855 arg1 males 1860:1864 males 1860:1864 males with TD and MetS 1860:1881 TREN treatment may be more effective in restoring androgen status and reducing cardiovascular risk in males with TD and MetS. 26584015 4 62 theme sham 684:687 arg1 surgery 689:695 sham surgery 684:695 sham surgery 684:695 After 8 weeks of feeding, rats underwent sham surgery or an orchiectomy (ORX). 26584015 1 63 theme TEST 259:262 arg1 deficiency 265:274 testosterone (TEST) deficiency 245:274 testosterone (TEST) deficiency (TD) 245:279 The increasing prevalence of obesity adds another dimension to the pathophysiology of testosterone (TEST) deficiency (TD) and potentially impairs the therapeutic efficacy of classical TEST replacement therapy. 26584015 1 63 theme TEST 259:262 arg1 TD 277:278 TD 277:278 TD 277:278 The increasing prevalence of obesity adds another dimension to the pathophysiology of testosterone (TEST) deficiency (TD) and potentially impairs the therapeutic efficacy of classical TEST replacement therapy. 26584015 12 64 contain have 1691:1694 arg1 therapy 1679:1685 TEST replacement therapy 1662:1685 TEST replacement therapy 1662:1685 We propose that TEST replacement therapy may have contraindications for males with TD and obesity-related MetS. 26584015 12 64 contain have 1691:1694 arg2 contraindications 1696:1712 contraindications 1696:1712 contraindications 1696:1712 We propose that TEST replacement therapy may have contraindications for males with TD and obesity-related MetS. 26584015 2 65 with TD 488:489 arg1 MetS 520:523 MetS 520:523 MetS 520:523 We investigated the therapeutic effects of selective androgen receptor modulation with trenbolone (TREN) in a model of TD with the metabolic syndrome (MetS). 26584015 2 65 with TD 488:489 arg1 syndrome 510:517 the metabolic syndrome 496:517 the metabolic syndrome (MetS) 496:524 We investigated the therapeutic effects of selective androgen receptor modulation with trenbolone (TREN) in a model of TD with the metabolic syndrome (MetS). 26584015 1 66 theme increasing 163:172 arg1 prevalence 174:183 The increasing prevalence 159:183 The increasing prevalence of obesity 159:194 The increasing prevalence of obesity adds another dimension to the pathophysiology of testosterone (TEST) deficiency (TD) and potentially impairs the therapeutic efficacy of classical TEST replacement therapy. 26584015 7 67 dep ischaemia 1000:1008 arg1 reperfusion 1010:1020 reperfusion 1010:1020 in vivo ischaemia reperfusion 992:1020 Infarct size was quantified to assess myocardial damage after in vivo ischaemia reperfusion, before cardiac and prostate histology was performed. 26584015 8 68 theme low 1220:1222 arg1 TEST 1236:1239 low circulating TEST 1220:1239 low circulating TEST 1220:1239 The HF/HS+ORX animals had increased sc and visceral adiposity; circulating triglycerides, cholesterol, and insulin; and myocardial damage, with low circulating TEST compared with CTRLs. 26584015 12 69 theme replacement 1667:1677 arg1 therapy 1679:1685 TEST replacement therapy 1662:1685 TEST replacement therapy 1662:1685 We propose that TEST replacement therapy may have contraindications for males with TD and obesity-related MetS. 26584015 3 70 theme Male 527:530 arg1 n=50 545:548 n=50 545:548 n=50 545:548 Male Wistar rats (n=50) were fed either a control standard rat chow (CTRL) or a high-fat/high-sucrose (HF/HS) diet. 26584015 3 70 theme Male 527:530 arg1 rats 539:542 Male Wistar rats 527:542 Male Wistar rats (n=50) 527:549 Male Wistar rats (n=50) were fed either a control standard rat chow (CTRL) or a high-fat/high-sucrose (HF/HS) diet. 26584015 12 71 theme obesity-related 1736:1750 arg1 MetS 1752:1755 TD and obesity-related MetS 1729:1755 TD and obesity-related MetS 1729:1755 We propose that TEST replacement therapy may have contraindications for males with TD and obesity-related MetS. 26584015 1 72 theme deficiency 265:274 arg1 pathophysiology 226:240 the pathophysiology 222:240 the pathophysiology of testosterone (TEST) deficiency (TD) 222:279 The increasing prevalence of obesity adds another dimension to the pathophysiology of testosterone (TEST) deficiency (TD) and potentially impairs the therapeutic efficacy of classical TEST replacement therapy. 26584015 7 73 dep in 992:993 arg1 vivo 995:998 vivo 995:998 vivo 995:998 Infarct size was quantified to assess myocardial damage after in vivo ischaemia reperfusion, before cardiac and prostate histology was performed. 26584015 1 74 theme therapy 360:366 arg1 efficacy 321:328 the therapeutic efficacy 305:328 the therapeutic efficacy of classical TEST replacement therapy 305:366 The increasing prevalence of obesity adds another dimension to the pathophysiology of testosterone (TEST) deficiency (TD) and potentially impairs the therapeutic efficacy of classical TEST replacement therapy. 26584015 5 75 theme 2-mg/kg·d 773:781 arg1 TEST 783:786 2-mg/kg·d TEST 773:786 2-mg/kg·d TEST 773:786 Alzet miniosmotic pumps containing either vehicle, 2-mg/kg·d TEST or 2-mg/kg·d TREN were implanted in HF/HS+ORX rats. 26584015 3 76 theme Wistar 532:537 arg1 n=50 545:548 n=50 545:548 n=50 545:548 Male Wistar rats (n=50) were fed either a control standard rat chow (CTRL) or a high-fat/high-sucrose (HF/HS) diet. 26584015 3 76 theme Wistar 532:537 arg1 rats 539:542 Male Wistar rats 527:542 Male Wistar rats (n=50) 527:549 Male Wistar rats (n=50) were fed either a control standard rat chow (CTRL) or a high-fat/high-sucrose (HF/HS) diet. 26584015 12 77 theme TEST 1662:1665 arg1 therapy 1679:1685 TEST replacement therapy 1662:1685 TEST replacement therapy 1662:1685 We propose that TEST replacement therapy may have contraindications for males with TD and obesity-related MetS. 26584015 9 78 theme sc 1317:1318 arg1 accumulation 1324:1335 sc fat accumulation 1317:1335 sc fat accumulation 1317:1335 Both TEST and TREN protected HF/HS+ORX animals against sc fat accumulation, hypercholesterolaemia, and myocardial damage. 27959934 6 0 theme Recombination 1051:1063 arg1 mapping 1065:1071 Recombination mapping 1051:1071 Recombination mapping 1051:1071 Recombination mapping localized the Kylb locus to a 5.5Mb region on chromosome 15A1, which contained 51 genes, including the natriuretic peptide receptor 3 (Npr3) gene. 27959934 9 1 theme hypertrophic 1818:1829 arg1 chondrocytes 1831:1842 hypertrophic chondrocytes 1818:1842 hypertrophic chondrocytes 1818:1842 NPR3 is a decoy receptor for C-type natriuretic peptide (CNP), which also binds to NPR2 and stimulates mitogen-activated protein kinase (MAPK) signaling, thereby increasing the number and size of hypertrophic chondrocytes. 27959934 8 2 theme plasma 1605:1610 arg1 membrane 1612:1619 the plasma membrane 1601:1619 the plasma membrane 1601:1619 Expression of wild-type NPR3 and the KYLB-associated Tyr209Asn NPR3 mutant in COS-7 cells demonstrated the mutant to be associated with abnormal N-linked glycosylation and retention in the endoplasmic reticulum that resulted in its absence from the plasma membrane. 27959934 8 3 from Expression 1356:1365 arg1 cells 1440:1444 COS-7 cells 1434:1444 COS-7 cells 1434:1444 Expression of wild-type NPR3 and the KYLB-associated Tyr209Asn NPR3 mutant in COS-7 cells demonstrated the mutant to be associated with abnormal N-linked glycosylation and retention in the endoplasmic reticulum that resulted in its absence from the plasma membrane. 27959934 2 4 theme mutagen 583:589 arg1 ENU 614:616 ENU 614:616 ENU 614:616 To overcome these limitations, we investigated 12 week old progeny of mice treated with the chemical mutagen N-ethyl-N-nitrosourea (ENU) using phenotypic assessments including dysmorphology, radiography, and dual-energy X-ray absorptiometry. 27959934 2 4 theme mutagen 583:589 arg1 N-ethyl-N-nitrosourea 591:611 the chemical mutagen N-ethyl-N-nitrosourea 570:611 the chemical mutagen N-ethyl-N-nitrosourea (ENU) 570:617 To overcome these limitations, we investigated 12 week old progeny of mice treated with the chemical mutagen N-ethyl-N-nitrosourea (ENU) using phenotypic assessments including dysmorphology, radiography, and dual-energy X-ray absorptiometry. 27959934 11 5 theme vertebrae 2313:2321 arg1 elongation 2295:2304 elongation 2295:2304 elongation of the vertebrae 2295:2321 Thus, we established a model of kyphosis due to a novel NPR3 mutation, in which loss of plasma membrane NPR3 expression results in increased MAPK pathway activation, causing elongation of the vertebrae and resulting in kyphosis. 27959934 10 6 theme KYLB 2105:2108 arg1 vertebrae 2110:2118 KYLB vertebrae 2105:2118 KYLB vertebrae 2105:2118 Histomorphometric analysis of KYLB vertebrae and tibiae showed delayed endochondral ossification and expansion of the hypertrophic zones of the growth plates, and immunohistochemistry revealed increased p38 MAPK phosphorylation throughout the growth plates of KYLB vertebrae. 27959934 0 7 theme MAPK 172:175 arg1 Pathway 187:193 the MAPK Signaling Pathway 168:193 the MAPK Signaling Pathway 168:193 Mice with an N-Ethyl-N-Nitrosourea (ENU) Induced Tyr209Asn Mutation in Natriuretic Peptide Receptor 3 (NPR3) Provide a Model for Kyphosis Associated with Activation of the MAPK Signaling Pathway. 27959934 4 8 theme unaffected 818:827 arg1 littermates 829:839 unaffected littermates 818:839 unaffected littermates 818:839 KYLB mice, when compared to unaffected littermates, had: thoraco-lumbar kyphosis, larger vertebrae, and increased body length and increased bone area. 27959934 11 9 theme membrane 2216:2223 arg1 expression 2230:2239 plasma membrane NPR3 expression 2209:2239 plasma membrane NPR3 expression 2209:2239 Thus, we established a model of kyphosis due to a novel NPR3 mutation, in which loss of plasma membrane NPR3 expression results in increased MAPK pathway activation, causing elongation of the vertebrae and resulting in kyphosis. 27959934 6 10 theme receptor 1196:1203 arg1 gene 1214:1217 the natriuretic peptide receptor 3 (Npr3) gene 1172:1217 the natriuretic peptide receptor 3 (Npr3) gene 1172:1217 Recombination mapping localized the Kylb locus to a 5.5Mb region on chromosome 15A1, which contained 51 genes, including the natriuretic peptide receptor 3 (Npr3) gene. 27959934 1 11 theme small 433:437 arg1 families 439:446 small families 433:446 small families 433:446 Non-syndromic kyphosis is a common disorder that is associated with significant morbidity and has a strong genetic involvement; however, the causative genes remain to be identified, as such studies are hampered by genetic heterogeneity, small families and various modes of inheritance. 27959934 5 12 from increases 975:983 arg1 content 1001:1007 bone mineral content 988:1007 bone mineral content 988:1007 In addition, female KYLB mice had increases in bone mineral content and plasma alkaline phosphatase activity. 27959934 5 12 from increases 975:983 arg1 activity 1041:1048 plasma alkaline phosphatase activity 1013:1048 plasma alkaline phosphatase activity 1013:1048 In addition, female KYLB mice had increases in bone mineral content and plasma alkaline phosphatase activity. 27959934 9 13 theme C-type 1651:1656 arg1 peptide 1670:1676 C-type natriuretic peptide 1651:1676 C-type natriuretic peptide (CNP) 1651:1682 NPR3 is a decoy receptor for C-type natriuretic peptide (CNP), which also binds to NPR2 and stimulates mitogen-activated protein kinase (MAPK) signaling, thereby increasing the number and size of hypertrophic chondrocytes. 27959934 9 13 theme C-type 1651:1656 arg1 CNP 1679:1681 CNP 1679:1681 CNP 1679:1681 NPR3 is a decoy receptor for C-type natriuretic peptide (CNP), which also binds to NPR2 and stimulates mitogen-activated protein kinase (MAPK) signaling, thereby increasing the number and size of hypertrophic chondrocytes. 27959934 7 14 theme consensus 1336:1344 arg1 sequence 1346:1353 an N-linked glycosylation consensus sequence 1310:1353 an N-linked glycosylation consensus sequence 1310:1353 DNA sequence analysis of Npr3 identified a missense mutation, Tyr209Asn, which introduced an N-linked glycosylation consensus sequence. 27959934 11 15 theme MAPK 2262:2265 arg1 activation 2275:2284 increased MAPK pathway activation 2252:2284 increased MAPK pathway activation 2252:2284 Thus, we established a model of kyphosis due to a novel NPR3 mutation, in which loss of plasma membrane NPR3 expression results in increased MAPK pathway activation, causing elongation of the vertebrae and resulting in kyphosis. 27959934 10 16 theme endochondral 1916:1927 arg1 ossification 1929:1940 delayed endochondral ossification 1908:1940 delayed endochondral ossification 1908:1940 Histomorphometric analysis of KYLB vertebrae and tibiae showed delayed endochondral ossification and expansion of the hypertrophic zones of the growth plates, and immunohistochemistry revealed increased p38 MAPK phosphorylation throughout the growth plates of KYLB vertebrae. 27959934 5 17 theme plasma 1013:1018 arg1 phosphatase 1029:1039 plasma alkaline phosphatase 1013:1039 plasma alkaline phosphatase activity 1013:1048 In addition, female KYLB mice had increases in bone mineral content and plasma alkaline phosphatase activity. 27959934 4 18 theme increased 894:902 arg1 length 909:914 increased body length 894:914 increased body length 894:914 KYLB mice, when compared to unaffected littermates, had: thoraco-lumbar kyphosis, larger vertebrae, and increased body length and increased bone area. 27959934 6 19 theme peptide 1188:1194 arg1 gene 1214:1217 the natriuretic peptide receptor 3 (Npr3) gene 1172:1217 the natriuretic peptide receptor 3 (Npr3) gene 1172:1217 Recombination mapping localized the Kylb locus to a 5.5Mb region on chromosome 15A1, which contained 51 genes, including the natriuretic peptide receptor 3 (Npr3) gene. 27959934 3 20 theme autosomal 753:761 arg1 KYLB 783:786 KYLB 783:786 KYLB 783:786 This identified a mouse with autosomal recessive kyphosis (KYLB). 27959934 3 20 theme autosomal 753:761 arg1 kyphosis 773:780 autosomal recessive kyphosis 753:780 autosomal recessive kyphosis (KYLB) 753:787 This identified a mouse with autosomal recessive kyphosis (KYLB). 27959934 5 21 theme phosphatase 1029:1039 arg1 activity 1041:1048 plasma alkaline phosphatase activity 1013:1048 plasma alkaline phosphatase activity 1013:1048 In addition, female KYLB mice had increases in bone mineral content and plasma alkaline phosphatase activity. 27959934 2 22 theme old 537:539 arg1 progeny 541:547 12 week old progeny 529:547 12 week old progeny of mice treated with the chemical mutagen N-ethyl-N-nitrosourea (ENU) 529:617 To overcome these limitations, we investigated 12 week old progeny of mice treated with the chemical mutagen N-ethyl-N-nitrosourea (ENU) using phenotypic assessments including dysmorphology, radiography, and dual-energy X-ray absorptiometry. 27959934 8 23 theme Tyr209Asn 1409:1417 arg1 mutant 1424:1429 the KYLB-associated Tyr209Asn NPR3 mutant 1389:1429 the KYLB-associated Tyr209Asn NPR3 mutant 1389:1429 Expression of wild-type NPR3 and the KYLB-associated Tyr209Asn NPR3 mutant in COS-7 cells demonstrated the mutant to be associated with abnormal N-linked glycosylation and retention in the endoplasmic reticulum that resulted in its absence from the plasma membrane. 27959934 5 24 theme bone 988:991 arg1 content 1001:1007 bone mineral content 988:1007 bone mineral content 988:1007 In addition, female KYLB mice had increases in bone mineral content and plasma alkaline phosphatase activity. 27959934 4 25 theme larger 872:877 arg1 vertebrae 879:887 larger vertebrae 872:887 larger vertebrae 872:887 KYLB mice, when compared to unaffected littermates, had: thoraco-lumbar kyphosis, larger vertebrae, and increased body length and increased bone area. 27959934 8 26 theme mutant 1424:1429 arg1 Expression 1356:1365 Expression 1356:1365 Expression of wild-type NPR3 and the KYLB-associated Tyr209Asn NPR3 mutant in COS-7 cells 1356:1444 Expression of wild-type NPR3 and the KYLB-associated Tyr209Asn NPR3 mutant in COS-7 cells demonstrated the mutant to be associated with abnormal N-linked glycosylation and retention in the endoplasmic reticulum that resulted in its absence from the plasma membrane. 27959934 10 27 theme growth 1989:1994 arg1 plates 1996:2001 the growth plates 1985:2001 the growth plates 1985:2001 Histomorphometric analysis of KYLB vertebrae and tibiae showed delayed endochondral ossification and expansion of the hypertrophic zones of the growth plates, and immunohistochemistry revealed increased p38 MAPK phosphorylation throughout the growth plates of KYLB vertebrae. 27959934 1 28 theme such 381:384 arg1 studies 386:392 such studies 381:392 such studies 381:392 Non-syndromic kyphosis is a common disorder that is associated with significant morbidity and has a strong genetic involvement; however, the causative genes remain to be identified, as such studies are hampered by genetic heterogeneity, small families and various modes of inheritance. 27959934 8 29 theme COS-7 1434:1438 arg1 cells 1440:1444 COS-7 cells 1434:1444 COS-7 cells 1434:1444 Expression of wild-type NPR3 and the KYLB-associated Tyr209Asn NPR3 mutant in COS-7 cells demonstrated the mutant to be associated with abnormal N-linked glycosylation and retention in the endoplasmic reticulum that resulted in its absence from the plasma membrane. 27959934 2 30 theme X-ray 702:706 arg1 absorptiometry 708:721 dual-energy X-ray absorptiometry 690:721 dual-energy X-ray absorptiometry 690:721 To overcome these limitations, we investigated 12 week old progeny of mice treated with the chemical mutagen N-ethyl-N-nitrosourea (ENU) using phenotypic assessments including dysmorphology, radiography, and dual-energy X-ray absorptiometry. 27959934 0 31 theme Tyr209Asn 49:57 arg1 Mutation 59:66 an N-Ethyl-N-Nitrosourea (ENU) Induced Tyr209Asn Mutation 10:66 an N-Ethyl-N-Nitrosourea (ENU) Induced Tyr209Asn Mutation in Natriuretic Peptide Receptor 3 (NPR3) 10:107 Mice with an N-Ethyl-N-Nitrosourea (ENU) Induced Tyr209Asn Mutation in Natriuretic Peptide Receptor 3 (NPR3) Provide a Model for Kyphosis Associated with Activation of the MAPK Signaling Pathway. 27959934 1 32 theme genetic 303:309 arg1 involvement 311:321 a strong genetic involvement 294:321 a strong genetic involvement 294:321 Non-syndromic kyphosis is a common disorder that is associated with significant morbidity and has a strong genetic involvement; however, the causative genes remain to be identified, as such studies are hampered by genetic heterogeneity, small families and various modes of inheritance. 27959934 4 33 contain had 842:844 arg1 mice 795:798 KYLB mice 790:798 KYLB mice 790:798 KYLB mice, when compared to unaffected littermates, had: thoraco-lumbar kyphosis, larger vertebrae, and increased body length and increased bone area. 27959934 4 33 contain had 842:844 arg2 vertebrae 879:887 larger vertebrae 872:887 larger vertebrae 872:887 KYLB mice, when compared to unaffected littermates, had: thoraco-lumbar kyphosis, larger vertebrae, and increased body length and increased bone area. 27959934 4 33 contain had 842:844 arg2 length 909:914 increased body length 894:914 increased body length 894:914 KYLB mice, when compared to unaffected littermates, had: thoraco-lumbar kyphosis, larger vertebrae, and increased body length and increased bone area. 27959934 4 33 contain had 842:844 arg2 kyphosis 862:869 : thoraco-lumbar kyphosis 845:869 : thoraco-lumbar kyphosis 845:869 KYLB mice, when compared to unaffected littermates, had: thoraco-lumbar kyphosis, larger vertebrae, and increased body length and increased bone area. 27959934 11 34 theme novel 2171:2175 arg1 mutation 2182:2189 a novel NPR3 mutation 2169:2189 a novel NPR3 mutation 2169:2189 Thus, we established a model of kyphosis due to a novel NPR3 mutation, in which loss of plasma membrane NPR3 expression results in increased MAPK pathway activation, causing elongation of the vertebrae and resulting in kyphosis. 27959934 3 35 with mouse 742:746 arg1 KYLB 783:786 KYLB 783:786 KYLB 783:786 This identified a mouse with autosomal recessive kyphosis (KYLB). 27959934 3 35 with mouse 742:746 arg1 kyphosis 773:780 autosomal recessive kyphosis 753:780 autosomal recessive kyphosis (KYLB) 753:787 This identified a mouse with autosomal recessive kyphosis (KYLB). 27959934 1 36 gly heterogeneity 418:430 arg1 inheritance 469:479 inheritance 469:479 inheritance 469:479 Non-syndromic kyphosis is a common disorder that is associated with significant morbidity and has a strong genetic involvement; however, the causative genes remain to be identified, as such studies are hampered by genetic heterogeneity, small families and various modes of inheritance. 27959934 0 37 theme Peptide 83:89 arg1 Receptor 91:98 Natriuretic Peptide Receptor 3 71:100 Natriuretic Peptide Receptor 3 (NPR3) 71:107 Mice with an N-Ethyl-N-Nitrosourea (ENU) Induced Tyr209Asn Mutation in Natriuretic Peptide Receptor 3 (NPR3) Provide a Model for Kyphosis Associated with Activation of the MAPK Signaling Pathway. 27959934 0 37 theme Peptide 83:89 arg1 NPR3 103:106 NPR3 103:106 NPR3 103:106 Mice with an N-Ethyl-N-Nitrosourea (ENU) Induced Tyr209Asn Mutation in Natriuretic Peptide Receptor 3 (NPR3) Provide a Model for Kyphosis Associated with Activation of the MAPK Signaling Pathway. 27959934 8 38 gly glycosylation 1510:1522 arg1 reticulum 1557:1565 the endoplasmic reticulum 1541:1565 the endoplasmic reticulum that resulted in its absence from the plasma membrane 1541:1619 Expression of wild-type NPR3 and the KYLB-associated Tyr209Asn NPR3 mutant in COS-7 cells demonstrated the mutant to be associated with abnormal N-linked glycosylation and retention in the endoplasmic reticulum that resulted in its absence from the plasma membrane. 27959934 4 39 theme increased 920:928 arg1 area 935:938 increased bone area 920:938 increased bone area 920:938 KYLB mice, when compared to unaffected littermates, had: thoraco-lumbar kyphosis, larger vertebrae, and increased body length and increased bone area. 27959934 11 40 theme NPR3 2225:2228 arg1 expression 2230:2239 plasma membrane NPR3 expression 2209:2239 plasma membrane NPR3 expression 2209:2239 Thus, we established a model of kyphosis due to a novel NPR3 mutation, in which loss of plasma membrane NPR3 expression results in increased MAPK pathway activation, causing elongation of the vertebrae and resulting in kyphosis. 27959934 1 41 theme causative 337:345 arg1 genes 347:351 the causative genes 333:351 the causative genes 333:351 Non-syndromic kyphosis is a common disorder that is associated with significant morbidity and has a strong genetic involvement; however, the causative genes remain to be identified, as such studies are hampered by genetic heterogeneity, small families and various modes of inheritance. 27959934 9 42 theme kinase 1751:1756 arg1 signaling 1765:1773 mitogen-activated protein kinase (MAPK) signaling 1725:1773 mitogen-activated protein kinase (MAPK) signaling 1725:1773 NPR3 is a decoy receptor for C-type natriuretic peptide (CNP), which also binds to NPR2 and stimulates mitogen-activated protein kinase (MAPK) signaling, thereby increasing the number and size of hypertrophic chondrocytes. 27959934 6 43 theme Npr3 1208:1211 arg1 gene 1214:1217 the natriuretic peptide receptor 3 (Npr3) gene 1172:1217 the natriuretic peptide receptor 3 (Npr3) gene 1172:1217 Recombination mapping localized the Kylb locus to a 5.5Mb region on chromosome 15A1, which contained 51 genes, including the natriuretic peptide receptor 3 (Npr3) gene. 27959934 8 44 theme N-linked 1501:1508 arg1 glycosylation 1510:1522 abnormal N-linked glycosylation 1492:1522 abnormal N-linked glycosylation 1492:1522 Expression of wild-type NPR3 and the KYLB-associated Tyr209Asn NPR3 mutant in COS-7 cells demonstrated the mutant to be associated with abnormal N-linked glycosylation and retention in the endoplasmic reticulum that resulted in its absence from the plasma membrane. 27959934 1 45 theme significant 264:274 arg1 morbidity 276:284 significant morbidity 264:284 significant morbidity 264:284 Non-syndromic kyphosis is a common disorder that is associated with significant morbidity and has a strong genetic involvement; however, the causative genes remain to be identified, as such studies are hampered by genetic heterogeneity, small families and various modes of inheritance. 27959934 7 46 theme Npr3 1245:1248 arg1 analysis 1233:1240 DNA sequence analysis 1220:1240 DNA sequence analysis of Npr3 1220:1248 DNA sequence analysis of Npr3 identified a missense mutation, Tyr209Asn, which introduced an N-linked glycosylation consensus sequence. 27959934 11 47 theme expression 2230:2239 arg1 loss 2201:2204 loss 2201:2204 loss of plasma membrane NPR3 expression 2201:2239 Thus, we established a model of kyphosis due to a novel NPR3 mutation, in which loss of plasma membrane NPR3 expression results in increased MAPK pathway activation, causing elongation of the vertebrae and resulting in kyphosis. 27959934 4 48 theme KYLB 790:793 arg1 mice 795:798 KYLB mice 790:798 KYLB mice 790:798 KYLB mice, when compared to unaffected littermates, had: thoraco-lumbar kyphosis, larger vertebrae, and increased body length and increased bone area. 27959934 6 49 from region 1109:1114 arg1 15A1 1130:1133 chromosome 15A1 1119:1133 chromosome 15A1 1119:1133 Recombination mapping localized the Kylb locus to a 5.5Mb region on chromosome 15A1, which contained 51 genes, including the natriuretic peptide receptor 3 (Npr3) gene. 27959934 7 50 link N-linked 1313:1320 arg1 sequence 1346:1353 an N-linked glycosylation consensus sequence 1310:1353 an N-linked glycosylation consensus sequence 1310:1353 DNA sequence analysis of Npr3 identified a missense mutation, Tyr209Asn, which introduced an N-linked glycosylation consensus sequence. 27959934 1 51 theme various 452:458 arg1 modes 460:464 various modes 452:464 various modes 452:464 Non-syndromic kyphosis is a common disorder that is associated with significant morbidity and has a strong genetic involvement; however, the causative genes remain to be identified, as such studies are hampered by genetic heterogeneity, small families and various modes of inheritance. 27959934 2 52 theme chemical 574:581 arg1 ENU 614:616 ENU 614:616 ENU 614:616 To overcome these limitations, we investigated 12 week old progeny of mice treated with the chemical mutagen N-ethyl-N-nitrosourea (ENU) using phenotypic assessments including dysmorphology, radiography, and dual-energy X-ray absorptiometry. 27959934 2 52 theme chemical 574:581 arg1 N-ethyl-N-nitrosourea 591:611 the chemical mutagen N-ethyl-N-nitrosourea 570:611 the chemical mutagen N-ethyl-N-nitrosourea (ENU) 570:617 To overcome these limitations, we investigated 12 week old progeny of mice treated with the chemical mutagen N-ethyl-N-nitrosourea (ENU) using phenotypic assessments including dysmorphology, radiography, and dual-energy X-ray absorptiometry. 27959934 7 53 theme DNA 1220:1222 arg1 analysis 1233:1240 DNA sequence analysis 1220:1240 DNA sequence analysis of Npr3 1220:1248 DNA sequence analysis of Npr3 identified a missense mutation, Tyr209Asn, which introduced an N-linked glycosylation consensus sequence. 27959934 10 54 theme MAPK 2052:2055 arg1 phosphorylation 2057:2071 increased p38 MAPK phosphorylation 2038:2071 increased p38 MAPK phosphorylation 2038:2071 Histomorphometric analysis of KYLB vertebrae and tibiae showed delayed endochondral ossification and expansion of the hypertrophic zones of the growth plates, and immunohistochemistry revealed increased p38 MAPK phosphorylation throughout the growth plates of KYLB vertebrae. 27959934 8 55 theme endoplasmic 1545:1555 arg1 reticulum 1557:1565 the endoplasmic reticulum 1541:1565 the endoplasmic reticulum that resulted in its absence from the plasma membrane 1541:1619 Expression of wild-type NPR3 and the KYLB-associated Tyr209Asn NPR3 mutant in COS-7 cells demonstrated the mutant to be associated with abnormal N-linked glycosylation and retention in the endoplasmic reticulum that resulted in its absence from the plasma membrane. 27959934 8 56 theme wild-type 1370:1378 arg1 NPR3 1380:1383 wild-type NPR3 1370:1383 wild-type NPR3 1370:1383 Expression of wild-type NPR3 and the KYLB-associated Tyr209Asn NPR3 mutant in COS-7 cells demonstrated the mutant to be associated with abnormal N-linked glycosylation and retention in the endoplasmic reticulum that resulted in its absence from the plasma membrane. 27959934 0 57 with Mice 0:3 arg1 Mutation 59:66 an N-Ethyl-N-Nitrosourea (ENU) Induced Tyr209Asn Mutation 10:66 an N-Ethyl-N-Nitrosourea (ENU) Induced Tyr209Asn Mutation in Natriuretic Peptide Receptor 3 (NPR3) 10:107 Mice with an N-Ethyl-N-Nitrosourea (ENU) Induced Tyr209Asn Mutation in Natriuretic Peptide Receptor 3 (NPR3) Provide a Model for Kyphosis Associated with Activation of the MAPK Signaling Pathway. 27959934 1 58 theme Non-syndromic 196:208 arg1 disorder 231:238 a common disorder 222:238 a common disorder that is associated with significant morbidity and has a strong genetic involvement 222:321 Non-syndromic kyphosis is a common disorder that is associated with significant morbidity and has a strong genetic involvement; however, the causative genes remain to be identified, as such studies are hampered by genetic heterogeneity, small families and various modes of inheritance. 27959934 1 58 theme Non-syndromic 196:208 arg1 kyphosis 210:217 Non-syndromic kyphosis 196:217 Non-syndromic kyphosis 196:217 Non-syndromic kyphosis is a common disorder that is associated with significant morbidity and has a strong genetic involvement; however, the causative genes remain to be identified, as such studies are hampered by genetic heterogeneity, small families and various modes of inheritance. 27959934 8 59 link N-linked 1501:1508 arg1 glycosylation 1510:1522 abnormal N-linked glycosylation 1492:1522 abnormal N-linked glycosylation 1492:1522 Expression of wild-type NPR3 and the KYLB-associated Tyr209Asn NPR3 mutant in COS-7 cells demonstrated the mutant to be associated with abnormal N-linked glycosylation and retention in the endoplasmic reticulum that resulted in its absence from the plasma membrane. 27959934 5 60 contain had 971:973 arg2 increases 975:983 increases 975:983 increases in bone mineral content and plasma alkaline phosphatase activity 975:1048 In addition, female KYLB mice had increases in bone mineral content and plasma alkaline phosphatase activity. 27959934 5 60 contain had 971:973 arg1 mice 966:969 female KYLB mice 954:969 female KYLB mice 954:969 In addition, female KYLB mice had increases in bone mineral content and plasma alkaline phosphatase activity. 27959934 11 61 theme kyphosis 2153:2160 arg1 model 2144:2148 a model 2142:2148 a model of kyphosis 2142:2160 Thus, we established a model of kyphosis due to a novel NPR3 mutation, in which loss of plasma membrane NPR3 expression results in increased MAPK pathway activation, causing elongation of the vertebrae and resulting in kyphosis. 27959934 5 62 theme KYLB 961:964 arg1 mice 966:969 female KYLB mice 954:969 female KYLB mice 954:969 In addition, female KYLB mice had increases in bone mineral content and plasma alkaline phosphatase activity. 27959934 10 63 theme growth 2088:2093 arg1 plates 2095:2100 the growth plates 2084:2100 the growth plates of KYLB vertebrae 2084:2118 Histomorphometric analysis of KYLB vertebrae and tibiae showed delayed endochondral ossification and expansion of the hypertrophic zones of the growth plates, and immunohistochemistry revealed increased p38 MAPK phosphorylation throughout the growth plates of KYLB vertebrae. 27959934 8 64 from retention 1528:1536 arg1 reticulum 1557:1565 the endoplasmic reticulum 1541:1565 the endoplasmic reticulum that resulted in its absence from the plasma membrane 1541:1619 Expression of wild-type NPR3 and the KYLB-associated Tyr209Asn NPR3 mutant in COS-7 cells demonstrated the mutant to be associated with abnormal N-linked glycosylation and retention in the endoplasmic reticulum that resulted in its absence from the plasma membrane. 27959934 1 65 theme common 224:229 arg1 disorder 231:238 a common disorder 222:238 a common disorder that is associated with significant morbidity and has a strong genetic involvement 222:321 Non-syndromic kyphosis is a common disorder that is associated with significant morbidity and has a strong genetic involvement; however, the causative genes remain to be identified, as such studies are hampered by genetic heterogeneity, small families and various modes of inheritance. 27959934 1 65 theme common 224:229 arg1 kyphosis 210:217 Non-syndromic kyphosis 196:217 Non-syndromic kyphosis 196:217 Non-syndromic kyphosis is a common disorder that is associated with significant morbidity and has a strong genetic involvement; however, the causative genes remain to be identified, as such studies are hampered by genetic heterogeneity, small families and various modes of inheritance. 27959934 2 66 theme mice 552:555 arg1 progeny 541:547 12 week old progeny 529:547 12 week old progeny of mice treated with the chemical mutagen N-ethyl-N-nitrosourea (ENU) 529:617 To overcome these limitations, we investigated 12 week old progeny of mice treated with the chemical mutagen N-ethyl-N-nitrosourea (ENU) using phenotypic assessments including dysmorphology, radiography, and dual-energy X-ray absorptiometry. 27959934 9 67 theme chondrocytes 1831:1842 arg1 size 1810:1813 size 1810:1813 size 1810:1813 NPR3 is a decoy receptor for C-type natriuretic peptide (CNP), which also binds to NPR2 and stimulates mitogen-activated protein kinase (MAPK) signaling, thereby increasing the number and size of hypertrophic chondrocytes. 27959934 9 67 theme chondrocytes 1831:1842 arg1 number 1799:1804 number 1799:1804 number 1799:1804 NPR3 is a decoy receptor for C-type natriuretic peptide (CNP), which also binds to NPR2 and stimulates mitogen-activated protein kinase (MAPK) signaling, thereby increasing the number and size of hypertrophic chondrocytes. 27959934 10 68 theme Histomorphometric 1845:1861 arg1 analysis 1863:1870 Histomorphometric analysis 1845:1870 Histomorphometric analysis of KYLB vertebrae and tibiae 1845:1899 Histomorphometric analysis of KYLB vertebrae and tibiae showed delayed endochondral ossification and expansion of the hypertrophic zones of the growth plates, and immunohistochemistry revealed increased p38 MAPK phosphorylation throughout the growth plates of KYLB vertebrae. 27959934 8 69 from glycosylation 1510:1522 arg1 reticulum 1557:1565 the endoplasmic reticulum 1541:1565 the endoplasmic reticulum that resulted in its absence from the plasma membrane 1541:1619 Expression of wild-type NPR3 and the KYLB-associated Tyr209Asn NPR3 mutant in COS-7 cells demonstrated the mutant to be associated with abnormal N-linked glycosylation and retention in the endoplasmic reticulum that resulted in its absence from the plasma membrane. 27959934 10 70 theme vertebrae 2110:2118 arg1 plates 2095:2100 the growth plates 2084:2100 the growth plates of KYLB vertebrae 2084:2118 Histomorphometric analysis of KYLB vertebrae and tibiae showed delayed endochondral ossification and expansion of the hypertrophic zones of the growth plates, and immunohistochemistry revealed increased p38 MAPK phosphorylation throughout the growth plates of KYLB vertebrae. 27959934 10 71 theme tibiae 1894:1899 arg1 analysis 1863:1870 Histomorphometric analysis 1845:1870 Histomorphometric analysis of KYLB vertebrae and tibiae 1845:1899 Histomorphometric analysis of KYLB vertebrae and tibiae showed delayed endochondral ossification and expansion of the hypertrophic zones of the growth plates, and immunohistochemistry revealed increased p38 MAPK phosphorylation throughout the growth plates of KYLB vertebrae. 27959934 0 72 theme Signaling 177:185 arg1 Pathway 187:193 the MAPK Signaling Pathway 168:193 the MAPK Signaling Pathway 168:193 Mice with an N-Ethyl-N-Nitrosourea (ENU) Induced Tyr209Asn Mutation in Natriuretic Peptide Receptor 3 (NPR3) Provide a Model for Kyphosis Associated with Activation of the MAPK Signaling Pathway. 27959934 1 73 theme genetic 410:416 arg1 heterogeneity 418:430 genetic heterogeneity 410:430 genetic heterogeneity 410:430 Non-syndromic kyphosis is a common disorder that is associated with significant morbidity and has a strong genetic involvement; however, the causative genes remain to be identified, as such studies are hampered by genetic heterogeneity, small families and various modes of inheritance. 27959934 9 74 theme decoy 1632:1636 arg1 NPR3 1622:1625 NPR3 1622:1625 NPR3 1622:1625 NPR3 is a decoy receptor for C-type natriuretic peptide (CNP), which also binds to NPR2 and stimulates mitogen-activated protein kinase (MAPK) signaling, thereby increasing the number and size of hypertrophic chondrocytes. 27959934 9 74 theme decoy 1632:1636 arg1 receptor 1638:1645 a decoy receptor 1630:1645 a decoy receptor for C-type natriuretic peptide (CNP), which also binds to NPR2 and stimulates mitogen-activated protein kinase (MAPK) signaling, thereby increasing the number and size of hypertrophic chondrocytes 1630:1842 NPR3 is a decoy receptor for C-type natriuretic peptide (CNP), which also binds to NPR2 and stimulates mitogen-activated protein kinase (MAPK) signaling, thereby increasing the number and size of hypertrophic chondrocytes. 27959934 6 75 theme chromosome 1119:1128 arg1 15A1 1130:1133 chromosome 15A1 1119:1133 chromosome 15A1 1119:1133 Recombination mapping localized the Kylb locus to a 5.5Mb region on chromosome 15A1, which contained 51 genes, including the natriuretic peptide receptor 3 (Npr3) gene. 27959934 11 76 theme plasma 2209:2214 arg1 expression 2230:2239 plasma membrane NPR3 expression 2209:2239 plasma membrane NPR3 expression 2209:2239 Thus, we established a model of kyphosis due to a novel NPR3 mutation, in which loss of plasma membrane NPR3 expression results in increased MAPK pathway activation, causing elongation of the vertebrae and resulting in kyphosis. 27959934 10 77 theme vertebrae 1880:1888 arg1 analysis 1863:1870 Histomorphometric analysis 1845:1870 Histomorphometric analysis of KYLB vertebrae and tibiae 1845:1899 Histomorphometric analysis of KYLB vertebrae and tibiae showed delayed endochondral ossification and expansion of the hypertrophic zones of the growth plates, and immunohistochemistry revealed increased p38 MAPK phosphorylation throughout the growth plates of KYLB vertebrae. 27959934 0 78 theme Pathway 187:193 arg1 Activation 154:163 Activation 154:163 Activation of the MAPK Signaling Pathway 154:193 Mice with an N-Ethyl-N-Nitrosourea (ENU) Induced Tyr209Asn Mutation in Natriuretic Peptide Receptor 3 (NPR3) Provide a Model for Kyphosis Associated with Activation of the MAPK Signaling Pathway. 27959934 11 79 theme increased 2252:2260 arg1 activation 2275:2284 increased MAPK pathway activation 2252:2284 increased MAPK pathway activation 2252:2284 Thus, we established a model of kyphosis due to a novel NPR3 mutation, in which loss of plasma membrane NPR3 expression results in increased MAPK pathway activation, causing elongation of the vertebrae and resulting in kyphosis. 27959934 1 80 contain has 290:292 arg1 disorder 231:238 a common disorder 222:238 a common disorder that is associated with significant morbidity and has a strong genetic involvement 222:321 Non-syndromic kyphosis is a common disorder that is associated with significant morbidity and has a strong genetic involvement; however, the causative genes remain to be identified, as such studies are hampered by genetic heterogeneity, small families and various modes of inheritance. 27959934 1 80 contain has 290:292 arg1 kyphosis 210:217 Non-syndromic kyphosis 196:217 Non-syndromic kyphosis 196:217 Non-syndromic kyphosis is a common disorder that is associated with significant morbidity and has a strong genetic involvement; however, the causative genes remain to be identified, as such studies are hampered by genetic heterogeneity, small families and various modes of inheritance. 27959934 1 80 contain has 290:292 arg2 involvement 311:321 a strong genetic involvement 294:321 a strong genetic involvement 294:321 Non-syndromic kyphosis is a common disorder that is associated with significant morbidity and has a strong genetic involvement; however, the causative genes remain to be identified, as such studies are hampered by genetic heterogeneity, small families and various modes of inheritance. 27959934 9 81 theme natriuretic 1658:1668 arg1 peptide 1670:1676 C-type natriuretic peptide 1651:1676 C-type natriuretic peptide (CNP) 1651:1682 NPR3 is a decoy receptor for C-type natriuretic peptide (CNP), which also binds to NPR2 and stimulates mitogen-activated protein kinase (MAPK) signaling, thereby increasing the number and size of hypertrophic chondrocytes. 27959934 9 81 theme natriuretic 1658:1668 arg1 CNP 1679:1681 CNP 1679:1681 CNP 1679:1681 NPR3 is a decoy receptor for C-type natriuretic peptide (CNP), which also binds to NPR2 and stimulates mitogen-activated protein kinase (MAPK) signaling, thereby increasing the number and size of hypertrophic chondrocytes. 27959934 8 82 theme KYLB-associated 1393:1407 arg1 mutant 1424:1429 the KYLB-associated Tyr209Asn NPR3 mutant 1389:1429 the KYLB-associated Tyr209Asn NPR3 mutant 1389:1429 Expression of wild-type NPR3 and the KYLB-associated Tyr209Asn NPR3 mutant in COS-7 cells demonstrated the mutant to be associated with abnormal N-linked glycosylation and retention in the endoplasmic reticulum that resulted in its absence from the plasma membrane. 27959934 10 83 theme delayed 1908:1914 arg1 ossification 1929:1940 delayed endochondral ossification 1908:1940 delayed endochondral ossification 1908:1940 Histomorphometric analysis of KYLB vertebrae and tibiae showed delayed endochondral ossification and expansion of the hypertrophic zones of the growth plates, and immunohistochemistry revealed increased p38 MAPK phosphorylation throughout the growth plates of KYLB vertebrae. 27959934 5 84 theme alkaline 1020:1027 arg1 phosphatase 1029:1039 plasma alkaline phosphatase 1013:1039 plasma alkaline phosphatase activity 1013:1048 In addition, female KYLB mice had increases in bone mineral content and plasma alkaline phosphatase activity. 27959934 8 85 theme NPR3 1419:1422 arg1 mutant 1424:1429 the KYLB-associated Tyr209Asn NPR3 mutant 1389:1429 the KYLB-associated Tyr209Asn NPR3 mutant 1389:1429 Expression of wild-type NPR3 and the KYLB-associated Tyr209Asn NPR3 mutant in COS-7 cells demonstrated the mutant to be associated with abnormal N-linked glycosylation and retention in the endoplasmic reticulum that resulted in its absence from the plasma membrane. 27959934 7 86 theme glycosylation 1322:1334 arg1 sequence 1346:1353 an N-linked glycosylation consensus sequence 1310:1353 an N-linked glycosylation consensus sequence 1310:1353 DNA sequence analysis of Npr3 identified a missense mutation, Tyr209Asn, which introduced an N-linked glycosylation consensus sequence. 27959934 3 87 theme recessive 763:771 arg1 KYLB 783:786 KYLB 783:786 KYLB 783:786 This identified a mouse with autosomal recessive kyphosis (KYLB). 27959934 3 87 theme recessive 763:771 arg1 kyphosis 773:780 autosomal recessive kyphosis 753:780 autosomal recessive kyphosis (KYLB) 753:787 This identified a mouse with autosomal recessive kyphosis (KYLB). 27959934 4 88 theme thoraco-lumbar 847:860 arg1 kyphosis 862:869 : thoraco-lumbar kyphosis 845:869 : thoraco-lumbar kyphosis 845:869 KYLB mice, when compared to unaffected littermates, had: thoraco-lumbar kyphosis, larger vertebrae, and increased body length and increased bone area. 27959934 5 89 theme mineral 993:999 arg1 content 1001:1007 bone mineral content 988:1007 bone mineral content 988:1007 In addition, female KYLB mice had increases in bone mineral content and plasma alkaline phosphatase activity. 27959934 6 90 theme 5.5Mb 1103:1107 arg1 region 1109:1114 a 5.5Mb region 1101:1114 a 5.5Mb region 1101:1114 Recombination mapping localized the Kylb locus to a 5.5Mb region on chromosome 15A1, which contained 51 genes, including the natriuretic peptide receptor 3 (Npr3) gene. 27959934 4 91 theme bone 930:933 arg1 area 935:938 increased bone area 920:938 increased bone area 920:938 KYLB mice, when compared to unaffected littermates, had: thoraco-lumbar kyphosis, larger vertebrae, and increased body length and increased bone area. 27959934 2 92 theme dual-energy 690:700 arg1 absorptiometry 708:721 dual-energy X-ray absorptiometry 690:721 dual-energy X-ray absorptiometry 690:721 To overcome these limitations, we investigated 12 week old progeny of mice treated with the chemical mutagen N-ethyl-N-nitrosourea (ENU) using phenotypic assessments including dysmorphology, radiography, and dual-energy X-ray absorptiometry. 27959934 10 93 theme zones 1976:1980 arg1 ossification 1929:1940 delayed endochondral ossification 1908:1940 delayed endochondral ossification 1908:1940 Histomorphometric analysis of KYLB vertebrae and tibiae showed delayed endochondral ossification and expansion of the hypertrophic zones of the growth plates, and immunohistochemistry revealed increased p38 MAPK phosphorylation throughout the growth plates of KYLB vertebrae. 27959934 10 93 theme zones 1976:1980 arg1 expansion 1946:1954 expansion 1946:1954 expansion of the hypertrophic zones of the growth plates 1946:2001 Histomorphometric analysis of KYLB vertebrae and tibiae showed delayed endochondral ossification and expansion of the hypertrophic zones of the growth plates, and immunohistochemistry revealed increased p38 MAPK phosphorylation throughout the growth plates of KYLB vertebrae. 27959934 0 94 theme Natriuretic 71:81 arg1 Receptor 91:98 Natriuretic Peptide Receptor 3 71:100 Natriuretic Peptide Receptor 3 (NPR3) 71:107 Mice with an N-Ethyl-N-Nitrosourea (ENU) Induced Tyr209Asn Mutation in Natriuretic Peptide Receptor 3 (NPR3) Provide a Model for Kyphosis Associated with Activation of the MAPK Signaling Pathway. 27959934 0 94 theme Natriuretic 71:81 arg1 NPR3 103:106 NPR3 103:106 NPR3 103:106 Mice with an N-Ethyl-N-Nitrosourea (ENU) Induced Tyr209Asn Mutation in Natriuretic Peptide Receptor 3 (NPR3) Provide a Model for Kyphosis Associated with Activation of the MAPK Signaling Pathway. 27959934 11 95 theme NPR3 2177:2180 arg1 mutation 2182:2189 a novel NPR3 mutation 2169:2189 a novel NPR3 mutation 2169:2189 Thus, we established a model of kyphosis due to a novel NPR3 mutation, in which loss of plasma membrane NPR3 expression results in increased MAPK pathway activation, causing elongation of the vertebrae and resulting in kyphosis. 27959934 4 96 theme body 904:907 arg1 length 909:914 increased body length 894:914 increased body length 894:914 KYLB mice, when compared to unaffected littermates, had: thoraco-lumbar kyphosis, larger vertebrae, and increased body length and increased bone area. 27959934 10 97 theme plates 1996:2001 arg1 zones 1976:1980 the hypertrophic zones 1959:1980 the hypertrophic zones of the growth plates 1959:2001 Histomorphometric analysis of KYLB vertebrae and tibiae showed delayed endochondral ossification and expansion of the hypertrophic zones of the growth plates, and immunohistochemistry revealed increased p38 MAPK phosphorylation throughout the growth plates of KYLB vertebrae. 27959934 9 98 dep number 1799:1804 arg1 the 1795:1797 the 1795:1797 the 1795:1797 NPR3 is a decoy receptor for C-type natriuretic peptide (CNP), which also binds to NPR2 and stimulates mitogen-activated protein kinase (MAPK) signaling, thereby increasing the number and size of hypertrophic chondrocytes. 27959934 10 99 theme increased 2038:2046 arg1 phosphorylation 2057:2071 increased p38 MAPK phosphorylation 2038:2071 increased p38 MAPK phosphorylation 2038:2071 Histomorphometric analysis of KYLB vertebrae and tibiae showed delayed endochondral ossification and expansion of the hypertrophic zones of the growth plates, and immunohistochemistry revealed increased p38 MAPK phosphorylation throughout the growth plates of KYLB vertebrae. 27959934 7 100 theme missense 1263:1270 arg1 Tyr209Asn 1282:1290 Tyr209Asn 1282:1290 Tyr209Asn 1282:1290 DNA sequence analysis of Npr3 identified a missense mutation, Tyr209Asn, which introduced an N-linked glycosylation consensus sequence. 27959934 7 100 theme missense 1263:1270 arg1 mutation 1272:1279 a missense mutation 1261:1279 a missense mutation 1261:1279 DNA sequence analysis of Npr3 identified a missense mutation, Tyr209Asn, which introduced an N-linked glycosylation consensus sequence. 27959934 9 101 theme protein 1743:1749 arg1 MAPK 1759:1762 MAPK 1759:1762 MAPK 1759:1762 NPR3 is a decoy receptor for C-type natriuretic peptide (CNP), which also binds to NPR2 and stimulates mitogen-activated protein kinase (MAPK) signaling, thereby increasing the number and size of hypertrophic chondrocytes. 27959934 9 101 theme protein 1743:1749 arg1 kinase 1751:1756 mitogen-activated protein kinase 1725:1756 mitogen-activated protein kinase (MAPK) signaling 1725:1773 NPR3 is a decoy receptor for C-type natriuretic peptide (CNP), which also binds to NPR2 and stimulates mitogen-activated protein kinase (MAPK) signaling, thereby increasing the number and size of hypertrophic chondrocytes. 27959934 8 102 theme abnormal 1492:1499 arg1 glycosylation 1510:1522 abnormal N-linked glycosylation 1492:1522 abnormal N-linked glycosylation 1492:1522 Expression of wild-type NPR3 and the KYLB-associated Tyr209Asn NPR3 mutant in COS-7 cells demonstrated the mutant to be associated with abnormal N-linked glycosylation and retention in the endoplasmic reticulum that resulted in its absence from the plasma membrane. 27959934 8 103 from membrane 1612:1619 arg1 absence 1588:1594 its absence 1584:1594 its absence from the plasma membrane 1584:1619 Expression of wild-type NPR3 and the KYLB-associated Tyr209Asn NPR3 mutant in COS-7 cells demonstrated the mutant to be associated with abnormal N-linked glycosylation and retention in the endoplasmic reticulum that resulted in its absence from the plasma membrane. 27959934 9 104 theme mitogen-activated 1725:1741 arg1 MAPK 1759:1762 MAPK 1759:1762 MAPK 1759:1762 NPR3 is a decoy receptor for C-type natriuretic peptide (CNP), which also binds to NPR2 and stimulates mitogen-activated protein kinase (MAPK) signaling, thereby increasing the number and size of hypertrophic chondrocytes. 27959934 9 104 theme mitogen-activated 1725:1741 arg1 kinase 1751:1756 mitogen-activated protein kinase 1725:1756 mitogen-activated protein kinase (MAPK) signaling 1725:1773 NPR3 is a decoy receptor for C-type natriuretic peptide (CNP), which also binds to NPR2 and stimulates mitogen-activated protein kinase (MAPK) signaling, thereby increasing the number and size of hypertrophic chondrocytes. 27959934 2 105 theme phenotypic 625:634 arg1 radiography 673:683 radiography 673:683 radiography 673:683 To overcome these limitations, we investigated 12 week old progeny of mice treated with the chemical mutagen N-ethyl-N-nitrosourea (ENU) using phenotypic assessments including dysmorphology, radiography, and dual-energy X-ray absorptiometry. 27959934 2 105 theme phenotypic 625:634 arg1 dysmorphology 658:670 dysmorphology 658:670 dysmorphology 658:670 To overcome these limitations, we investigated 12 week old progeny of mice treated with the chemical mutagen N-ethyl-N-nitrosourea (ENU) using phenotypic assessments including dysmorphology, radiography, and dual-energy X-ray absorptiometry. 27959934 2 105 theme phenotypic 625:634 arg1 assessments 636:646 phenotypic assessments 625:646 phenotypic assessments including dysmorphology, radiography, and dual-energy X-ray absorptiometry 625:721 To overcome these limitations, we investigated 12 week old progeny of mice treated with the chemical mutagen N-ethyl-N-nitrosourea (ENU) using phenotypic assessments including dysmorphology, radiography, and dual-energy X-ray absorptiometry. 27959934 2 105 theme phenotypic 625:634 arg1 absorptiometry 708:721 dual-energy X-ray absorptiometry 690:721 dual-energy X-ray absorptiometry 690:721 To overcome these limitations, we investigated 12 week old progeny of mice treated with the chemical mutagen N-ethyl-N-nitrosourea (ENU) using phenotypic assessments including dysmorphology, radiography, and dual-energy X-ray absorptiometry. 27959934 7 106 theme N-linked 1313:1320 arg1 sequence 1346:1353 an N-linked glycosylation consensus sequence 1310:1353 an N-linked glycosylation consensus sequence 1310:1353 DNA sequence analysis of Npr3 identified a missense mutation, Tyr209Asn, which introduced an N-linked glycosylation consensus sequence. 27959934 11 107 theme pathway 2267:2273 arg1 activation 2275:2284 increased MAPK pathway activation 2252:2284 increased MAPK pathway activation 2252:2284 Thus, we established a model of kyphosis due to a novel NPR3 mutation, in which loss of plasma membrane NPR3 expression results in increased MAPK pathway activation, causing elongation of the vertebrae and resulting in kyphosis. 27959934 7 108 theme sequence 1224:1231 arg1 analysis 1233:1240 DNA sequence analysis 1220:1240 DNA sequence analysis of Npr3 1220:1248 DNA sequence analysis of Npr3 identified a missense mutation, Tyr209Asn, which introduced an N-linked glycosylation consensus sequence. 27959934 6 109 contain contained 1142:1150 arg1 region 1109:1114 a 5.5Mb region 1101:1114 a 5.5Mb region 1101:1114 Recombination mapping localized the Kylb locus to a 5.5Mb region on chromosome 15A1, which contained 51 genes, including the natriuretic peptide receptor 3 (Npr3) gene. 27959934 6 109 contain contained 1142:1150 arg2 gene 1214:1217 the natriuretic peptide receptor 3 (Npr3) gene 1172:1217 the natriuretic peptide receptor 3 (Npr3) gene 1172:1217 Recombination mapping localized the Kylb locus to a 5.5Mb region on chromosome 15A1, which contained 51 genes, including the natriuretic peptide receptor 3 (Npr3) gene. 27959934 6 109 contain contained 1142:1150 arg2 genes 1155:1159 51 genes 1152:1159 51 genes 1152:1159 Recombination mapping localized the Kylb locus to a 5.5Mb region on chromosome 15A1, which contained 51 genes, including the natriuretic peptide receptor 3 (Npr3) gene. 27959934 0 110 theme Induced 41:47 arg1 Mutation 59:66 an N-Ethyl-N-Nitrosourea (ENU) Induced Tyr209Asn Mutation 10:66 an N-Ethyl-N-Nitrosourea (ENU) Induced Tyr209Asn Mutation in Natriuretic Peptide Receptor 3 (NPR3) 10:107 Mice with an N-Ethyl-N-Nitrosourea (ENU) Induced Tyr209Asn Mutation in Natriuretic Peptide Receptor 3 (NPR3) Provide a Model for Kyphosis Associated with Activation of the MAPK Signaling Pathway. 27959934 10 111 theme hypertrophic 1963:1974 arg1 zones 1976:1980 the hypertrophic zones 1959:1980 the hypertrophic zones of the growth plates 1959:2001 Histomorphometric analysis of KYLB vertebrae and tibiae showed delayed endochondral ossification and expansion of the hypertrophic zones of the growth plates, and immunohistochemistry revealed increased p38 MAPK phosphorylation throughout the growth plates of KYLB vertebrae. 27959934 0 112 from Mutation 59:66 arg1 Receptor 91:98 Natriuretic Peptide Receptor 3 71:100 Natriuretic Peptide Receptor 3 (NPR3) 71:107 Mice with an N-Ethyl-N-Nitrosourea (ENU) Induced Tyr209Asn Mutation in Natriuretic Peptide Receptor 3 (NPR3) Provide a Model for Kyphosis Associated with Activation of the MAPK Signaling Pathway. 27959934 0 112 from Mutation 59:66 arg1 NPR3 103:106 NPR3 103:106 NPR3 103:106 Mice with an N-Ethyl-N-Nitrosourea (ENU) Induced Tyr209Asn Mutation in Natriuretic Peptide Receptor 3 (NPR3) Provide a Model for Kyphosis Associated with Activation of the MAPK Signaling Pathway. 27959934 1 113 theme strong 296:301 arg1 involvement 311:321 a strong genetic involvement 294:321 a strong genetic involvement 294:321 Non-syndromic kyphosis is a common disorder that is associated with significant morbidity and has a strong genetic involvement; however, the causative genes remain to be identified, as such studies are hampered by genetic heterogeneity, small families and various modes of inheritance. 27959934 6 114 theme natriuretic 1176:1186 arg1 gene 1214:1217 the natriuretic peptide receptor 3 (Npr3) gene 1172:1217 the natriuretic peptide receptor 3 (Npr3) gene 1172:1217 Recombination mapping localized the Kylb locus to a 5.5Mb region on chromosome 15A1, which contained 51 genes, including the natriuretic peptide receptor 3 (Npr3) gene. 27959934 6 115 theme Kylb 1087:1090 arg1 locus 1092:1096 the Kylb locus 1083:1096 the Kylb locus 1083:1096 Recombination mapping localized the Kylb locus to a 5.5Mb region on chromosome 15A1, which contained 51 genes, including the natriuretic peptide receptor 3 (Npr3) gene. 27959934 10 116 theme p38 2048:2050 arg1 phosphorylation 2057:2071 increased p38 MAPK phosphorylation 2038:2071 increased p38 MAPK phosphorylation 2038:2071 Histomorphometric analysis of KYLB vertebrae and tibiae showed delayed endochondral ossification and expansion of the hypertrophic zones of the growth plates, and immunohistochemistry revealed increased p38 MAPK phosphorylation throughout the growth plates of KYLB vertebrae. 27959934 1 117 theme inheritance 469:479 arg1 modes 460:464 various modes 452:464 various modes 452:464 Non-syndromic kyphosis is a common disorder that is associated with significant morbidity and has a strong genetic involvement; however, the causative genes remain to be identified, as such studies are hampered by genetic heterogeneity, small families and various modes of inheritance. 27959934 1 117 theme inheritance 469:479 arg1 heterogeneity 418:430 genetic heterogeneity 410:430 genetic heterogeneity 410:430 Non-syndromic kyphosis is a common disorder that is associated with significant morbidity and has a strong genetic involvement; however, the causative genes remain to be identified, as such studies are hampered by genetic heterogeneity, small families and various modes of inheritance. 27959934 1 117 theme inheritance 469:479 arg1 families 439:446 small families 433:446 small families 433:446 Non-syndromic kyphosis is a common disorder that is associated with significant morbidity and has a strong genetic involvement; however, the causative genes remain to be identified, as such studies are hampered by genetic heterogeneity, small families and various modes of inheritance. 27959934 5 118 theme female 954:959 arg1 mice 966:969 female KYLB mice 954:969 female KYLB mice 954:969 In addition, female KYLB mice had increases in bone mineral content and plasma alkaline phosphatase activity. 27959934 10 119 theme KYLB 1875:1878 arg1 vertebrae 1880:1888 KYLB vertebrae 1875:1888 KYLB vertebrae 1875:1888 Histomorphometric analysis of KYLB vertebrae and tibiae showed delayed endochondral ossification and expansion of the hypertrophic zones of the growth plates, and immunohistochemistry revealed increased p38 MAPK phosphorylation throughout the growth plates of KYLB vertebrae. 27959934 8 120 theme NPR3 1380:1383 arg1 Expression 1356:1365 Expression 1356:1365 Expression of wild-type NPR3 and the KYLB-associated Tyr209Asn NPR3 mutant in COS-7 cells 1356:1444 Expression of wild-type NPR3 and the KYLB-associated Tyr209Asn NPR3 mutant in COS-7 cells demonstrated the mutant to be associated with abnormal N-linked glycosylation and retention in the endoplasmic reticulum that resulted in its absence from the plasma membrane. 27316967 2 0 theme proteins 562:569 arg1 presence 525:532 the presence 521:532 the presence 521:532 In the present study, we introduced unmarked in-frame deletions into the corresponding genes of S. gordonii DL1, verified the presence (or absence) of the encoded proteins on the resulting mutant strains, and compared these strains with wild-type strain DL1 for growth and glycan foraging in saliva. 27316967 2 0 theme proteins 562:569 arg1 absence 538:544 absence 538:544 absence 538:544 In the present study, we introduced unmarked in-frame deletions into the corresponding genes of S. gordonii DL1, verified the presence (or absence) of the encoded proteins on the resulting mutant strains, and compared these strains with wild-type strain DL1 for growth and glycan foraging in saliva. 27316967 5 1 theme surface 1324:1330 arg1 BgaA 1332:1335 cell surface BgaA 1319:1335 cell surface BgaA alone or together with either StrH or EndoD 1319:1379 The binding of ECA to PRG was also abolished in saliva cultures of mutants that expressed cell surface BgaA alone or together with either StrH or EndoD. 27316967 1 2 theme cell 233:236 arg1 homologs 270:277 homologs 270:277 homologs of pneumococcal β-galactosidase (BgaA), β-N-acetylglucosaminidase (StrH), and endo-β-N-acetylglucosaminidase D (EndoD) 270:396 UNLABELLED The growth of the oral commensal Streptococcus gordonii in saliva may depend on a number of glycoside hydrolases (GHs), including three cell wall-anchored proteins that are homologs of pneumococcal β-galactosidase (BgaA), β-N-acetylglucosaminidase (StrH), and endo-β-N-acetylglucosaminidase D (EndoD). 27316967 1 2 theme cell 233:236 arg1 proteins 252:259 three cell wall-anchored proteins 227:259 three cell wall-anchored proteins that are homologs of pneumococcal β-galactosidase (BgaA), β-N-acetylglucosaminidase (StrH), and endo-β-N-acetylglucosaminidase D (EndoD) 227:396 UNLABELLED The growth of the oral commensal Streptococcus gordonii in saliva may depend on a number of glycoside hydrolases (GHs), including three cell wall-anchored proteins that are homologs of pneumococcal β-galactosidase (BgaA), β-N-acetylglucosaminidase (StrH), and endo-β-N-acetylglucosaminidase D (EndoD). 27316967 12 3 theme proline-rich 2572:2583 arg1 step 2648:2651 an essential first step 2629:2651 an essential first step in salivary glycan foraging 2629:2679 The results indicate that the growth of S. gordonii DL1 depends to a significant extent on sequential action of these cell surface GHs on N-linked glycans of basic proline-rich salivary glycoproteins, which appears to be an essential first step in salivary glycan foraging. 27316967 12 3 theme proline-rich 2572:2583 arg1 glycoproteins 2594:2606 basic proline-rich salivary glycoproteins 2566:2606 basic proline-rich salivary glycoproteins 2566:2606 The results indicate that the growth of S. gordonii DL1 depends to a significant extent on sequential action of these cell surface GHs on N-linked glycans of basic proline-rich salivary glycoproteins, which appears to be an essential first step in salivary glycan foraging. 27316967 7 4 theme first 1662:1666 arg1 BgaA 1668:1671 first BgaA 1662:1671 first BgaA 1662:1671 The findings indicate that the growth of S. gordonii DL1 in saliva depends to a significant extent on the sequential actions of first BgaA and then StrH and EndoD on N-linked glycans of PRG. 27316967 11 5 theme in-frame 2185:2192 arg1 deletions 2194:2202 unmarked in-frame deletions 2176:2202 unmarked in-frame deletions in the corresponding genes 2176:2229 In the present study, we introduced unmarked in-frame deletions in the corresponding genes, verified the presence (or absence) of encoded proteins on the resulting mutant strains, and compared these strains with wild-type DL1 for growth and glycan foraging in saliva. 27316967 9 6 theme community 1977:1985 arg1 members 1954:1960 different members 1944:1960 different members 1944:1960 Little is known, however, about how specific salivary components are attacked and utilized by different members of the biofilm community, such as Streptococcus gordonii. 27316967 9 6 theme community 1977:1985 arg1 Streptococcus 1996:2008 Streptococcus gordonii 1996:2017 Streptococcus gordonii 1996:2017 Little is known, however, about how specific salivary components are attacked and utilized by different members of the biofilm community, such as Streptococcus gordonii. 27316967 11 7 from DL1 2362:2364 arg1 saliva 2400:2405 saliva 2400:2405 saliva 2400:2405 In the present study, we introduced unmarked in-frame deletions in the corresponding genes, verified the presence (or absence) of encoded proteins on the resulting mutant strains, and compared these strains with wild-type DL1 for growth and glycan foraging in saliva. 27316967 2 8 theme mutant 588:593 arg1 strains 595:601 the resulting mutant strains 574:601 the resulting mutant strains 574:601 In the present study, we introduced unmarked in-frame deletions into the corresponding genes of S. gordonii DL1, verified the presence (or absence) of the encoded proteins on the resulting mutant strains, and compared these strains with wild-type strain DL1 for growth and glycan foraging in saliva. 27316967 2 9 from DL1 653:655 arg1 saliva 691:696 saliva 691:696 saliva 691:696 In the present study, we introduced unmarked in-frame deletions into the corresponding genes of S. gordonii DL1, verified the presence (or absence) of the encoded proteins on the resulting mutant strains, and compared these strains with wild-type strain DL1 for growth and glycan foraging in saliva. 27316967 12 10 theme S. 2448:2449 arg1 DL1 2460:2462 S. gordonii DL1 2448:2462 S. gordonii DL1 2448:2462 The results indicate that the growth of S. gordonii DL1 depends to a significant extent on sequential action of these cell surface GHs on N-linked glycans of basic proline-rich salivary glycoproteins, which appears to be an essential first step in salivary glycan foraging. 27316967 5 11 theme mutants 1296:1302 arg1 cultures 1284:1291 saliva cultures 1277:1291 saliva cultures of mutants that expressed cell surface BgaA alone or together with either StrH or EndoD 1277:1379 The binding of ECA to PRG was also abolished in saliva cultures of mutants that expressed cell surface BgaA alone or together with either StrH or EndoD. 27316967 6 12 theme GNA 1414:1416 arg1 binding 1418:1424 GNA binding 1414:1424 GNA binding 1414:1424 However, the subsequent loss of GNA binding was seen only in saliva cocultures of different mutants that together expressed all three cell surface GHs. 27316967 12 13 theme N-linked 2546:2553 arg1 glycans 2555:2561 N-linked glycans 2546:2561 N-linked glycans of basic proline-rich salivary glycoproteins, which appears to be an essential first step in salivary glycan foraging 2546:2679 The results indicate that the growth of S. gordonii DL1 depends to a significant extent on sequential action of these cell surface GHs on N-linked glycans of basic proline-rich salivary glycoproteins, which appears to be an essential first step in salivary glycan foraging. 27316967 10 14 theme host 2126:2129 arg1 glycans 2131:2137 host glycans 2126:2137 host glycans 2126:2137 Streptococcus gordonii DL1 has three cell wall-anchored glycoside hydrolases that are predicted to act on host glycans. 27316967 11 15 attach presence 2245:2252 arg1 strains 2311:2317 the resulting mutant strains 2290:2317 the resulting mutant strains 2290:2317 In the present study, we introduced unmarked in-frame deletions in the corresponding genes, verified the presence (or absence) of encoded proteins on the resulting mutant strains, and compared these strains with wild-type DL1 for growth and glycan foraging in saliva. 27316967 11 15 attach presence 2245:2252 arg2 proteins 2278:2285 encoded proteins 2270:2285 encoded proteins 2270:2285 In the present study, we introduced unmarked in-frame deletions in the corresponding genes, verified the presence (or absence) of encoded proteins on the resulting mutant strains, and compared these strains with wild-type DL1 for growth and glycan foraging in saliva. 27316967 11 16 theme present 2147:2153 arg1 study 2155:2159 the present study 2143:2159 the present study 2143:2159 In the present study, we introduced unmarked in-frame deletions in the corresponding genes, verified the presence (or absence) of encoded proteins on the resulting mutant strains, and compared these strains with wild-type DL1 for growth and glycan foraging in saliva. 27316967 8 17 theme oral 1751:1754 arg1 bacteria 1756:1763 oral bacteria 1751:1763 oral bacteria 1751:1763 IMPORTANCE The ability of oral bacteria to grow on salivary glycoproteins is critical for dental plaque biofilm development. 27316967 1 18 theme endo-β-N-acetylglucosaminidase 357:386 arg1 EndoD 391:395 EndoD 391:395 EndoD 391:395 UNLABELLED The growth of the oral commensal Streptococcus gordonii in saliva may depend on a number of glycoside hydrolases (GHs), including three cell wall-anchored proteins that are homologs of pneumococcal β-galactosidase (BgaA), β-N-acetylglucosaminidase (StrH), and endo-β-N-acetylglucosaminidase D (EndoD). 27316967 1 18 theme endo-β-N-acetylglucosaminidase 357:386 arg1 D 388:388 endo-β-N-acetylglucosaminidase D 357:388 endo-β-N-acetylglucosaminidase D (EndoD) 357:396 UNLABELLED The growth of the oral commensal Streptococcus gordonii in saliva may depend on a number of glycoside hydrolases (GHs), including three cell wall-anchored proteins that are homologs of pneumococcal β-galactosidase (BgaA), β-N-acetylglucosaminidase (StrH), and endo-β-N-acetylglucosaminidase D (EndoD). 27316967 1 19 theme glycoside 189:197 arg1 GHs 211:213 GHs 211:213 GHs 211:213 UNLABELLED The growth of the oral commensal Streptococcus gordonii in saliva may depend on a number of glycoside hydrolases (GHs), including three cell wall-anchored proteins that are homologs of pneumococcal β-galactosidase (BgaA), β-N-acetylglucosaminidase (StrH), and endo-β-N-acetylglucosaminidase D (EndoD). 27316967 1 19 theme glycoside 189:197 arg1 hydrolases 199:208 glycoside hydrolases 189:208 glycoside hydrolases (GHs) 189:214 UNLABELLED The growth of the oral commensal Streptococcus gordonii in saliva may depend on a number of glycoside hydrolases (GHs), including three cell wall-anchored proteins that are homologs of pneumococcal β-galactosidase (BgaA), β-N-acetylglucosaminidase (StrH), and endo-β-N-acetylglucosaminidase D (EndoD). 27316967 1 19 theme glycoside 189:197 arg1 proteins 252:259 three cell wall-anchored proteins 227:259 three cell wall-anchored proteins that are homologs of pneumococcal β-galactosidase (BgaA), β-N-acetylglucosaminidase (StrH), and endo-β-N-acetylglucosaminidase D (EndoD) 227:396 UNLABELLED The growth of the oral commensal Streptococcus gordonii in saliva may depend on a number of glycoside hydrolases (GHs), including three cell wall-anchored proteins that are homologs of pneumococcal β-galactosidase (BgaA), β-N-acetylglucosaminidase (StrH), and endo-β-N-acetylglucosaminidase D (EndoD). 27316967 12 20 theme cell 2526:2529 arg1 GHs 2539:2541 these cell surface GHs 2520:2541 these cell surface GHs 2520:2541 The results indicate that the growth of S. gordonii DL1 depends to a significant extent on sequential action of these cell surface GHs on N-linked glycans of basic proline-rich salivary glycoproteins, which appears to be an essential first step in salivary glycan foraging. 27316967 4 21 theme proline-rich 1018:1029 arg1 PRG 1046:1048 PRG 1046:1048 PRG 1046:1048 The only notable change in the salivary proteome associated with this reduction of growth was a downward shift in the apparent molecular masses of basic proline-rich glycoproteins (PRG), which was accompanied by the loss of lectin binding sites for galactose-specific Erythrina cristagalli agglutinin (ECA) and mannose-specific Galanthus nivalis agglutinin (GNA). 27316967 4 21 theme proline-rich 1018:1029 arg1 glycoproteins 1031:1043 basic proline-rich glycoproteins 1012:1043 basic proline-rich glycoproteins (PRG) 1012:1049 The only notable change in the salivary proteome associated with this reduction of growth was a downward shift in the apparent molecular masses of basic proline-rich glycoproteins (PRG), which was accompanied by the loss of lectin binding sites for galactose-specific Erythrina cristagalli agglutinin (ECA) and mannose-specific Galanthus nivalis agglutinin (GNA). 27316967 3 22 theme wild-type 723:731 arg1 DL1 733:735 wild-type DL1 723:735 wild-type DL1 723:735 The overnight growth of wild-type DL1 was reduced 3- to 10-fold by the deletion of any one or two genes and approximately 20-fold by the deletion of all three genes. 27316967 3 23 dep 3- 749:750 arg1 to 752:753 to 752:753 to 752:753 The overnight growth of wild-type DL1 was reduced 3- to 10-fold by the deletion of any one or two genes and approximately 20-fold by the deletion of all three genes. 27316967 6 24 theme mutants 1474:1480 arg1 cocultures 1450:1459 saliva cocultures 1443:1459 saliva cocultures of different mutants that together expressed all three cell surface GHs 1443:1531 However, the subsequent loss of GNA binding was seen only in saliva cocultures of different mutants that together expressed all three cell surface GHs. 27316967 11 25 theme wild-type 2352:2360 arg1 DL1 2362:2364 wild-type DL1 2352:2364 wild-type DL1 for growth and glycan foraging in saliva 2352:2405 In the present study, we introduced unmarked in-frame deletions in the corresponding genes, verified the presence (or absence) of encoded proteins on the resulting mutant strains, and compared these strains with wild-type DL1 for growth and glycan foraging in saliva. 27316967 12 26 theme DL1 2460:2462 arg1 growth 2438:2443 the growth 2434:2443 the growth of S. gordonii DL1 2434:2462 The results indicate that the growth of S. gordonii DL1 depends to a significant extent on sequential action of these cell surface GHs on N-linked glycans of basic proline-rich salivary glycoproteins, which appears to be an essential first step in salivary glycan foraging. 27316967 10 27 contain has 2047:2049 arg1 DL1 2043:2045 Streptococcus gordonii DL1 2020:2045 Streptococcus gordonii DL1 2020:2045 Streptococcus gordonii DL1 has three cell wall-anchored glycoside hydrolases that are predicted to act on host glycans. 27316967 10 27 contain has 2047:2049 arg2 hydrolases 2086:2095 three cell wall-anchored glycoside hydrolases 2051:2095 three cell wall-anchored glycoside hydrolases that are predicted to act on host glycans 2051:2137 Streptococcus gordonii DL1 has three cell wall-anchored glycoside hydrolases that are predicted to act on host glycans. 27316967 1 28 theme oral 115:118 arg1 gordonii 144:151 the oral commensal Streptococcus gordonii 111:151 the oral commensal Streptococcus gordonii 111:151 UNLABELLED The growth of the oral commensal Streptococcus gordonii in saliva may depend on a number of glycoside hydrolases (GHs), including three cell wall-anchored proteins that are homologs of pneumococcal β-galactosidase (BgaA), β-N-acetylglucosaminidase (StrH), and endo-β-N-acetylglucosaminidase D (EndoD). 27316967 12 29 theme sequential 2499:2508 arg1 action 2510:2515 sequential action 2499:2515 sequential action of these cell surface GHs on N-linked glycans of basic proline-rich salivary glycoproteins, which appears to be an essential first step in salivary glycan foraging 2499:2679 The results indicate that the growth of S. gordonii DL1 depends to a significant extent on sequential action of these cell surface GHs on N-linked glycans of basic proline-rich salivary glycoproteins, which appears to be an essential first step in salivary glycan foraging. 27316967 2 30 theme strain 646:651 arg1 DL1 653:655 wild-type strain DL1 636:655 wild-type strain DL1 for growth and glycan foraging in saliva 636:696 In the present study, we introduced unmarked in-frame deletions into the corresponding genes of S. gordonii DL1, verified the presence (or absence) of the encoded proteins on the resulting mutant strains, and compared these strains with wild-type strain DL1 for growth and glycan foraging in saliva. 27316967 6 31 theme saliva 1443:1448 arg1 cocultures 1450:1459 saliva cocultures 1443:1459 saliva cocultures of different mutants that together expressed all three cell surface GHs 1443:1531 However, the subsequent loss of GNA binding was seen only in saliva cocultures of different mutants that together expressed all three cell surface GHs. 27316967 1 32 theme Streptococcus 130:142 arg1 gordonii 144:151 the oral commensal Streptococcus gordonii 111:151 the oral commensal Streptococcus gordonii 111:151 UNLABELLED The growth of the oral commensal Streptococcus gordonii in saliva may depend on a number of glycoside hydrolases (GHs), including three cell wall-anchored proteins that are homologs of pneumococcal β-galactosidase (BgaA), β-N-acetylglucosaminidase (StrH), and endo-β-N-acetylglucosaminidase D (EndoD). 27316967 12 33 theme glycan 2665:2670 arg1 foraging 2672:2679 salivary glycan foraging 2656:2679 salivary glycan foraging 2656:2679 The results indicate that the growth of S. gordonii DL1 depends to a significant extent on sequential action of these cell surface GHs on N-linked glycans of basic proline-rich salivary glycoproteins, which appears to be an essential first step in salivary glycan foraging. 27316967 7 34 from growth 1565:1570 arg1 saliva 1594:1599 saliva 1594:1599 saliva 1594:1599 The findings indicate that the growth of S. gordonii DL1 in saliva depends to a significant extent on the sequential actions of first BgaA and then StrH and EndoD on N-linked glycans of PRG. 27316967 2 35 theme present 406:412 arg1 study 414:418 the present study 402:418 the present study 402:418 In the present study, we introduced unmarked in-frame deletions into the corresponding genes of S. gordonii DL1, verified the presence (or absence) of the encoded proteins on the resulting mutant strains, and compared these strains with wild-type strain DL1 for growth and glycan foraging in saliva. 27316967 4 36 from shift 970:974 arg1 masses 1002:1007 the apparent molecular masses 979:1007 the apparent molecular masses of basic proline-rich glycoproteins (PRG) 979:1049 The only notable change in the salivary proteome associated with this reduction of growth was a downward shift in the apparent molecular masses of basic proline-rich glycoproteins (PRG), which was accompanied by the loss of lectin binding sites for galactose-specific Erythrina cristagalli agglutinin (ECA) and mannose-specific Galanthus nivalis agglutinin (GNA). 27316967 7 37 theme DL1 1587:1589 arg1 growth 1565:1570 the growth 1561:1570 the growth of S. gordonii DL1 in saliva 1561:1599 The findings indicate that the growth of S. gordonii DL1 in saliva depends to a significant extent on the sequential actions of first BgaA and then StrH and EndoD on N-linked glycans of PRG. 27316967 4 38 theme salivary 896:903 arg1 proteome 905:912 the salivary proteome 892:912 the salivary proteome associated with this reduction of growth 892:953 The only notable change in the salivary proteome associated with this reduction of growth was a downward shift in the apparent molecular masses of basic proline-rich glycoproteins (PRG), which was accompanied by the loss of lectin binding sites for galactose-specific Erythrina cristagalli agglutinin (ECA) and mannose-specific Galanthus nivalis agglutinin (GNA). 27316967 10 39 theme gordonii 2034:2041 arg1 DL1 2043:2045 Streptococcus gordonii DL1 2020:2045 Streptococcus gordonii DL1 2020:2045 Streptococcus gordonii DL1 has three cell wall-anchored glycoside hydrolases that are predicted to act on host glycans. 27316967 8 40 theme dental 1815:1820 arg1 development 1837:1847 dental plaque biofilm development 1815:1847 dental plaque biofilm development 1815:1847 IMPORTANCE The ability of oral bacteria to grow on salivary glycoproteins is critical for dental plaque biofilm development. 27316967 1 41 theme β-N-acetylglucosaminidase 319:343 arg1 homologs 270:277 homologs 270:277 homologs of pneumococcal β-galactosidase (BgaA), β-N-acetylglucosaminidase (StrH), and endo-β-N-acetylglucosaminidase D (EndoD) 270:396 UNLABELLED The growth of the oral commensal Streptococcus gordonii in saliva may depend on a number of glycoside hydrolases (GHs), including three cell wall-anchored proteins that are homologs of pneumococcal β-galactosidase (BgaA), β-N-acetylglucosaminidase (StrH), and endo-β-N-acetylglucosaminidase D (EndoD). 27316967 1 41 theme β-N-acetylglucosaminidase 319:343 arg1 proteins 252:259 three cell wall-anchored proteins 227:259 three cell wall-anchored proteins that are homologs of pneumococcal β-galactosidase (BgaA), β-N-acetylglucosaminidase (StrH), and endo-β-N-acetylglucosaminidase D (EndoD) 227:396 UNLABELLED The growth of the oral commensal Streptococcus gordonii in saliva may depend on a number of glycoside hydrolases (GHs), including three cell wall-anchored proteins that are homologs of pneumococcal β-galactosidase (BgaA), β-N-acetylglucosaminidase (StrH), and endo-β-N-acetylglucosaminidase D (EndoD). 27316967 7 42 theme S. 1575:1576 arg1 DL1 1587:1589 S. gordonii DL1 1575:1589 S. gordonii DL1 1575:1589 The findings indicate that the growth of S. gordonii DL1 in saliva depends to a significant extent on the sequential actions of first BgaA and then StrH and EndoD on N-linked glycans of PRG. 27316967 9 43 theme salivary 1895:1902 arg1 components 1904:1913 specific salivary components 1886:1913 specific salivary components 1886:1913 Little is known, however, about how specific salivary components are attacked and utilized by different members of the biofilm community, such as Streptococcus gordonii. 27316967 2 44 theme DL1 507:509 arg1 genes 486:490 the corresponding genes 468:490 the corresponding genes of S. gordonii DL1 468:509 In the present study, we introduced unmarked in-frame deletions into the corresponding genes of S. gordonii DL1, verified the presence (or absence) of the encoded proteins on the resulting mutant strains, and compared these strains with wild-type strain DL1 for growth and glycan foraging in saliva. 27316967 11 45 theme mutant 2304:2309 arg1 strains 2311:2317 the resulting mutant strains 2290:2317 the resulting mutant strains 2290:2317 In the present study, we introduced unmarked in-frame deletions in the corresponding genes, verified the presence (or absence) of encoded proteins on the resulting mutant strains, and compared these strains with wild-type DL1 for growth and glycan foraging in saliva. 27316967 4 46 theme Erythrina 1133:1141 arg1 ECA 1167:1169 ECA 1167:1169 ECA 1167:1169 The only notable change in the salivary proteome associated with this reduction of growth was a downward shift in the apparent molecular masses of basic proline-rich glycoproteins (PRG), which was accompanied by the loss of lectin binding sites for galactose-specific Erythrina cristagalli agglutinin (ECA) and mannose-specific Galanthus nivalis agglutinin (GNA). 27316967 4 46 theme Erythrina 1133:1141 arg1 agglutinin 1155:1164 galactose-specific Erythrina cristagalli agglutinin 1114:1164 galactose-specific Erythrina cristagalli agglutinin (ECA) 1114:1170 The only notable change in the salivary proteome associated with this reduction of growth was a downward shift in the apparent molecular masses of basic proline-rich glycoproteins (PRG), which was accompanied by the loss of lectin binding sites for galactose-specific Erythrina cristagalli agglutinin (ECA) and mannose-specific Galanthus nivalis agglutinin (GNA). 27316967 8 47 theme biofilm 1829:1835 arg1 development 1837:1847 dental plaque biofilm development 1815:1847 dental plaque biofilm development 1815:1847 IMPORTANCE The ability of oral bacteria to grow on salivary glycoproteins is critical for dental plaque biofilm development. 27316967 6 48 theme cell 1516:1519 arg1 GHs 1529:1531 all three cell surface GHs 1506:1531 all three cell surface GHs 1506:1531 However, the subsequent loss of GNA binding was seen only in saliva cocultures of different mutants that together expressed all three cell surface GHs. 27316967 2 49 theme S. 495:496 arg1 DL1 507:509 S. gordonii DL1 495:509 S. gordonii DL1 495:509 In the present study, we introduced unmarked in-frame deletions into the corresponding genes of S. gordonii DL1, verified the presence (or absence) of the encoded proteins on the resulting mutant strains, and compared these strains with wild-type strain DL1 for growth and glycan foraging in saliva. 27316967 10 50 theme cell 2057:2060 arg1 hydrolases 2086:2095 three cell wall-anchored glycoside hydrolases 2051:2095 three cell wall-anchored glycoside hydrolases that are predicted to act on host glycans 2051:2137 Streptococcus gordonii DL1 has three cell wall-anchored glycoside hydrolases that are predicted to act on host glycans. 27316967 4 51 theme binding 1096:1102 arg1 sites 1104:1108 lectin binding sites 1089:1108 lectin binding sites for galactose-specific Erythrina cristagalli agglutinin (ECA) and mannose-specific Galanthus nivalis agglutinin (GNA) 1089:1226 The only notable change in the salivary proteome associated with this reduction of growth was a downward shift in the apparent molecular masses of basic proline-rich glycoproteins (PRG), which was accompanied by the loss of lectin binding sites for galactose-specific Erythrina cristagalli agglutinin (ECA) and mannose-specific Galanthus nivalis agglutinin (GNA). 27316967 0 52 theme Cell 0:3 arg1 Hydrolases 23:32 Cell Surface Glycoside Hydrolases 0:32 Cell Surface Glycoside Hydrolases of Streptococcus gordonii 0:58 Cell Surface Glycoside Hydrolases of Streptococcus gordonii Promote Growth in Saliva. 27316967 12 53 theme GHs 2539:2541 arg1 action 2510:2515 sequential action 2499:2515 sequential action of these cell surface GHs on N-linked glycans of basic proline-rich salivary glycoproteins, which appears to be an essential first step in salivary glycan foraging 2499:2679 The results indicate that the growth of S. gordonii DL1 depends to a significant extent on sequential action of these cell surface GHs on N-linked glycans of basic proline-rich salivary glycoproteins, which appears to be an essential first step in salivary glycan foraging. 27316967 9 54 theme specific 1886:1893 arg1 components 1904:1913 specific salivary components 1886:1913 specific salivary components 1886:1913 Little is known, however, about how specific salivary components are attacked and utilized by different members of the biofilm community, such as Streptococcus gordonii. 27316967 0 55 theme Glycoside 13:21 arg1 Hydrolases 23:32 Cell Surface Glycoside Hydrolases 0:32 Cell Surface Glycoside Hydrolases of Streptococcus gordonii 0:58 Cell Surface Glycoside Hydrolases of Streptococcus gordonii Promote Growth in Saliva. 27316967 12 56 theme glycoproteins 2594:2606 arg1 glycans 2555:2561 N-linked glycans 2546:2561 N-linked glycans of basic proline-rich salivary glycoproteins, which appears to be an essential first step in salivary glycan foraging 2546:2679 The results indicate that the growth of S. gordonii DL1 depends to a significant extent on sequential action of these cell surface GHs on N-linked glycans of basic proline-rich salivary glycoproteins, which appears to be an essential first step in salivary glycan foraging. 27316967 4 57 theme Galanthus 1193:1201 arg1 GNA 1223:1225 GNA 1223:1225 GNA 1223:1225 The only notable change in the salivary proteome associated with this reduction of growth was a downward shift in the apparent molecular masses of basic proline-rich glycoproteins (PRG), which was accompanied by the loss of lectin binding sites for galactose-specific Erythrina cristagalli agglutinin (ECA) and mannose-specific Galanthus nivalis agglutinin (GNA). 27316967 4 57 theme Galanthus 1193:1201 arg1 agglutinin 1211:1220 mannose-specific Galanthus nivalis agglutinin 1176:1220 mannose-specific Galanthus nivalis agglutinin (GNA) 1176:1226 The only notable change in the salivary proteome associated with this reduction of growth was a downward shift in the apparent molecular masses of basic proline-rich glycoproteins (PRG), which was accompanied by the loss of lectin binding sites for galactose-specific Erythrina cristagalli agglutinin (ECA) and mannose-specific Galanthus nivalis agglutinin (GNA). 27316967 1 58 theme pneumococcal 282:293 arg1 β-galactosidase 295:309 pneumococcal β-galactosidase 282:309 pneumococcal β-galactosidase (BgaA) 282:316 UNLABELLED The growth of the oral commensal Streptococcus gordonii in saliva may depend on a number of glycoside hydrolases (GHs), including three cell wall-anchored proteins that are homologs of pneumococcal β-galactosidase (BgaA), β-N-acetylglucosaminidase (StrH), and endo-β-N-acetylglucosaminidase D (EndoD). 27316967 1 58 theme pneumococcal 282:293 arg1 BgaA 312:315 BgaA 312:315 BgaA 312:315 UNLABELLED The growth of the oral commensal Streptococcus gordonii in saliva may depend on a number of glycoside hydrolases (GHs), including three cell wall-anchored proteins that are homologs of pneumococcal β-galactosidase (BgaA), β-N-acetylglucosaminidase (StrH), and endo-β-N-acetylglucosaminidase D (EndoD). 27316967 12 59 theme salivary 2585:2592 arg1 step 2648:2651 an essential first step 2629:2651 an essential first step in salivary glycan foraging 2629:2679 The results indicate that the growth of S. gordonii DL1 depends to a significant extent on sequential action of these cell surface GHs on N-linked glycans of basic proline-rich salivary glycoproteins, which appears to be an essential first step in salivary glycan foraging. 27316967 12 59 theme salivary 2585:2592 arg1 glycoproteins 2594:2606 basic proline-rich salivary glycoproteins 2566:2606 basic proline-rich salivary glycoproteins 2566:2606 The results indicate that the growth of S. gordonii DL1 depends to a significant extent on sequential action of these cell surface GHs on N-linked glycans of basic proline-rich salivary glycoproteins, which appears to be an essential first step in salivary glycan foraging. 27316967 2 60 theme unmarked 435:442 arg1 deletions 453:461 unmarked in-frame deletions 435:461 unmarked in-frame deletions 435:461 In the present study, we introduced unmarked in-frame deletions into the corresponding genes of S. gordonii DL1, verified the presence (or absence) of the encoded proteins on the resulting mutant strains, and compared these strains with wild-type strain DL1 for growth and glycan foraging in saliva. 27316967 12 61 theme salivary 2656:2663 arg1 foraging 2672:2679 salivary glycan foraging 2656:2679 salivary glycan foraging 2656:2679 The results indicate that the growth of S. gordonii DL1 depends to a significant extent on sequential action of these cell surface GHs on N-linked glycans of basic proline-rich salivary glycoproteins, which appears to be an essential first step in salivary glycan foraging. 27316967 5 62 theme saliva 1277:1282 arg1 cultures 1284:1291 saliva cultures 1277:1291 saliva cultures of mutants that expressed cell surface BgaA alone or together with either StrH or EndoD 1277:1379 The binding of ECA to PRG was also abolished in saliva cultures of mutants that expressed cell surface BgaA alone or together with either StrH or EndoD. 27316967 0 63 theme gordonii 51:58 arg1 Hydrolases 23:32 Cell Surface Glycoside Hydrolases 0:32 Cell Surface Glycoside Hydrolases of Streptococcus gordonii 0:58 Cell Surface Glycoside Hydrolases of Streptococcus gordonii Promote Growth in Saliva. 27316967 12 64 from extent 2489:2494 arg1 action 2510:2515 sequential action 2499:2515 sequential action of these cell surface GHs on N-linked glycans of basic proline-rich salivary glycoproteins, which appears to be an essential first step in salivary glycan foraging 2499:2679 The results indicate that the growth of S. gordonii DL1 depends to a significant extent on sequential action of these cell surface GHs on N-linked glycans of basic proline-rich salivary glycoproteins, which appears to be an essential first step in salivary glycan foraging. 27316967 12 65 theme surface 2531:2537 arg1 GHs 2539:2541 these cell surface GHs 2520:2541 these cell surface GHs 2520:2541 The results indicate that the growth of S. gordonii DL1 depends to a significant extent on sequential action of these cell surface GHs on N-linked glycans of basic proline-rich salivary glycoproteins, which appears to be an essential first step in salivary glycan foraging. 27316967 7 66 from extent 1626:1631 arg1 actions 1651:1657 the sequential actions 1636:1657 the sequential actions of first BgaA and then StrH and EndoD on N-linked glycans of PRG 1636:1722 The findings indicate that the growth of S. gordonii DL1 in saliva depends to a significant extent on the sequential actions of first BgaA and then StrH and EndoD on N-linked glycans of PRG. 27316967 4 67 theme apparent 983:990 arg1 masses 1002:1007 the apparent molecular masses 979:1007 the apparent molecular masses of basic proline-rich glycoproteins (PRG) 979:1049 The only notable change in the salivary proteome associated with this reduction of growth was a downward shift in the apparent molecular masses of basic proline-rich glycoproteins (PRG), which was accompanied by the loss of lectin binding sites for galactose-specific Erythrina cristagalli agglutinin (ECA) and mannose-specific Galanthus nivalis agglutinin (GNA). 27316967 11 68 from presence 2245:2252 arg1 strains 2311:2317 the resulting mutant strains 2290:2317 the resulting mutant strains 2290:2317 In the present study, we introduced unmarked in-frame deletions in the corresponding genes, verified the presence (or absence) of encoded proteins on the resulting mutant strains, and compared these strains with wild-type DL1 for growth and glycan foraging in saliva. 27316967 11 69 theme encoded 2270:2276 arg1 proteins 2278:2285 encoded proteins 2270:2285 encoded proteins 2270:2285 In the present study, we introduced unmarked in-frame deletions in the corresponding genes, verified the presence (or absence) of encoded proteins on the resulting mutant strains, and compared these strains with wild-type DL1 for growth and glycan foraging in saliva. 27316967 9 70 theme different 1944:1952 arg1 members 1954:1960 different members 1944:1960 different members 1944:1960 Little is known, however, about how specific salivary components are attacked and utilized by different members of the biofilm community, such as Streptococcus gordonii. 27316967 9 70 theme different 1944:1952 arg1 Streptococcus 1996:2008 Streptococcus gordonii 1996:2017 Streptococcus gordonii 1996:2017 Little is known, however, about how specific salivary components are attacked and utilized by different members of the biofilm community, such as Streptococcus gordonii. 27316967 7 71 theme BgaA 1668:1671 arg1 actions 1651:1657 the sequential actions 1636:1657 the sequential actions of first BgaA and then StrH and EndoD on N-linked glycans of PRG 1636:1722 The findings indicate that the growth of S. gordonii DL1 in saliva depends to a significant extent on the sequential actions of first BgaA and then StrH and EndoD on N-linked glycans of PRG. 27316967 7 72 from actions 1651:1657 arg1 glycans 1709:1715 N-linked glycans 1700:1715 N-linked glycans of PRG 1700:1722 The findings indicate that the growth of S. gordonii DL1 in saliva depends to a significant extent on the sequential actions of first BgaA and then StrH and EndoD on N-linked glycans of PRG. 27316967 4 73 theme downward 961:968 arg1 shift 970:974 a downward shift 959:974 a downward shift 959:974 The only notable change in the salivary proteome associated with this reduction of growth was a downward shift in the apparent molecular masses of basic proline-rich glycoproteins (PRG), which was accompanied by the loss of lectin binding sites for galactose-specific Erythrina cristagalli agglutinin (ECA) and mannose-specific Galanthus nivalis agglutinin (GNA). 27316967 4 73 theme downward 961:968 arg1 change 882:887 The only notable change 865:887 The only notable change in the salivary proteome associated with this reduction of growth 865:953 The only notable change in the salivary proteome associated with this reduction of growth was a downward shift in the apparent molecular masses of basic proline-rich glycoproteins (PRG), which was accompanied by the loss of lectin binding sites for galactose-specific Erythrina cristagalli agglutinin (ECA) and mannose-specific Galanthus nivalis agglutinin (GNA). 27316967 2 74 theme encoded 554:560 arg1 proteins 562:569 the encoded proteins 550:569 the encoded proteins 550:569 In the present study, we introduced unmarked in-frame deletions into the corresponding genes of S. gordonii DL1, verified the presence (or absence) of the encoded proteins on the resulting mutant strains, and compared these strains with wild-type strain DL1 for growth and glycan foraging in saliva. 27316967 11 75 theme unmarked 2176:2183 arg1 deletions 2194:2202 unmarked in-frame deletions 2176:2202 unmarked in-frame deletions in the corresponding genes 2176:2229 In the present study, we introduced unmarked in-frame deletions in the corresponding genes, verified the presence (or absence) of encoded proteins on the resulting mutant strains, and compared these strains with wild-type DL1 for growth and glycan foraging in saliva. 27316967 12 76 theme first 2642:2646 arg1 step 2648:2651 an essential first step 2629:2651 an essential first step in salivary glycan foraging 2629:2679 The results indicate that the growth of S. gordonii DL1 depends to a significant extent on sequential action of these cell surface GHs on N-linked glycans of basic proline-rich salivary glycoproteins, which appears to be an essential first step in salivary glycan foraging. 27316967 12 76 theme first 2642:2646 arg1 glycoproteins 2594:2606 basic proline-rich salivary glycoproteins 2566:2606 basic proline-rich salivary glycoproteins 2566:2606 The results indicate that the growth of S. gordonii DL1 depends to a significant extent on sequential action of these cell surface GHs on N-linked glycans of basic proline-rich salivary glycoproteins, which appears to be an essential first step in salivary glycan foraging. 27316967 9 77 theme biofilm 1969:1975 arg1 community 1977:1985 the biofilm community 1965:1985 the biofilm community 1965:1985 Little is known, however, about how specific salivary components are attacked and utilized by different members of the biofilm community, such as Streptococcus gordonii. 27316967 11 78 theme proteins 2278:2285 arg1 presence 2245:2252 the presence 2241:2252 the presence 2241:2252 In the present study, we introduced unmarked in-frame deletions in the corresponding genes, verified the presence (or absence) of encoded proteins on the resulting mutant strains, and compared these strains with wild-type DL1 for growth and glycan foraging in saliva. 27316967 11 78 theme proteins 2278:2285 arg1 absence 2258:2264 absence 2258:2264 absence 2258:2264 In the present study, we introduced unmarked in-frame deletions in the corresponding genes, verified the presence (or absence) of encoded proteins on the resulting mutant strains, and compared these strains with wild-type DL1 for growth and glycan foraging in saliva. 27316967 1 79 theme wall-anchored 238:250 arg1 homologs 270:277 homologs 270:277 homologs of pneumococcal β-galactosidase (BgaA), β-N-acetylglucosaminidase (StrH), and endo-β-N-acetylglucosaminidase D (EndoD) 270:396 UNLABELLED The growth of the oral commensal Streptococcus gordonii in saliva may depend on a number of glycoside hydrolases (GHs), including three cell wall-anchored proteins that are homologs of pneumococcal β-galactosidase (BgaA), β-N-acetylglucosaminidase (StrH), and endo-β-N-acetylglucosaminidase D (EndoD). 27316967 1 79 theme wall-anchored 238:250 arg1 proteins 252:259 three cell wall-anchored proteins 227:259 three cell wall-anchored proteins that are homologs of pneumococcal β-galactosidase (BgaA), β-N-acetylglucosaminidase (StrH), and endo-β-N-acetylglucosaminidase D (EndoD) 227:396 UNLABELLED The growth of the oral commensal Streptococcus gordonii in saliva may depend on a number of glycoside hydrolases (GHs), including three cell wall-anchored proteins that are homologs of pneumococcal β-galactosidase (BgaA), β-N-acetylglucosaminidase (StrH), and endo-β-N-acetylglucosaminidase D (EndoD). 27316967 12 80 theme basic 2566:2570 arg1 step 2648:2651 an essential first step 2629:2651 an essential first step in salivary glycan foraging 2629:2679 The results indicate that the growth of S. gordonii DL1 depends to a significant extent on sequential action of these cell surface GHs on N-linked glycans of basic proline-rich salivary glycoproteins, which appears to be an essential first step in salivary glycan foraging. 27316967 12 80 theme basic 2566:2570 arg1 glycoproteins 2594:2606 basic proline-rich salivary glycoproteins 2566:2606 basic proline-rich salivary glycoproteins 2566:2606 The results indicate that the growth of S. gordonii DL1 depends to a significant extent on sequential action of these cell surface GHs on N-linked glycans of basic proline-rich salivary glycoproteins, which appears to be an essential first step in salivary glycan foraging. 27316967 7 81 theme sequential 1640:1649 arg1 actions 1651:1657 the sequential actions 1636:1657 the sequential actions of first BgaA and then StrH and EndoD on N-linked glycans of PRG 1636:1722 The findings indicate that the growth of S. gordonii DL1 in saliva depends to a significant extent on the sequential actions of first BgaA and then StrH and EndoD on N-linked glycans of PRG. 27316967 11 82 from deletions 2194:2202 arg1 genes 2225:2229 the corresponding genes 2207:2229 the corresponding genes 2207:2229 In the present study, we introduced unmarked in-frame deletions in the corresponding genes, verified the presence (or absence) of encoded proteins on the resulting mutant strains, and compared these strains with wild-type DL1 for growth and glycan foraging in saliva. 27316967 6 83 theme binding 1418:1424 arg1 loss 1406:1409 the subsequent loss 1391:1409 the subsequent loss of GNA binding 1391:1424 However, the subsequent loss of GNA binding was seen only in saliva cocultures of different mutants that together expressed all three cell surface GHs. 27316967 2 84 theme resulting 578:586 arg1 strains 595:601 the resulting mutant strains 574:601 the resulting mutant strains 574:601 In the present study, we introduced unmarked in-frame deletions into the corresponding genes of S. gordonii DL1, verified the presence (or absence) of the encoded proteins on the resulting mutant strains, and compared these strains with wild-type strain DL1 for growth and glycan foraging in saliva. 27316967 7 85 theme significant 1614:1624 arg1 extent 1626:1631 a significant extent 1612:1631 a significant extent on the sequential actions of first BgaA and then StrH and EndoD on N-linked glycans of PRG 1612:1722 The findings indicate that the growth of S. gordonii DL1 in saliva depends to a significant extent on the sequential actions of first BgaA and then StrH and EndoD on N-linked glycans of PRG. 27316967 4 86 theme basic 1012:1016 arg1 PRG 1046:1048 PRG 1046:1048 PRG 1046:1048 The only notable change in the salivary proteome associated with this reduction of growth was a downward shift in the apparent molecular masses of basic proline-rich glycoproteins (PRG), which was accompanied by the loss of lectin binding sites for galactose-specific Erythrina cristagalli agglutinin (ECA) and mannose-specific Galanthus nivalis agglutinin (GNA). 27316967 4 86 theme basic 1012:1016 arg1 glycoproteins 1031:1043 basic proline-rich glycoproteins 1012:1043 basic proline-rich glycoproteins (PRG) 1012:1049 The only notable change in the salivary proteome associated with this reduction of growth was a downward shift in the apparent molecular masses of basic proline-rich glycoproteins (PRG), which was accompanied by the loss of lectin binding sites for galactose-specific Erythrina cristagalli agglutinin (ECA) and mannose-specific Galanthus nivalis agglutinin (GNA). 27316967 3 87 theme overnight 703:711 arg1 growth 713:718 The overnight growth 699:718 The overnight growth of wild-type DL1 699:735 The overnight growth of wild-type DL1 was reduced 3- to 10-fold by the deletion of any one or two genes and approximately 20-fold by the deletion of all three genes. 27316967 8 88 theme bacteria 1756:1763 arg1 ability 1740:1746 The ability 1736:1746 The ability of oral bacteria 1736:1763 IMPORTANCE The ability of oral bacteria to grow on salivary glycoproteins is critical for dental plaque biofilm development. 27316967 5 89 theme cell 1319:1322 arg1 BgaA 1332:1335 cell surface BgaA 1319:1335 cell surface BgaA alone or together with either StrH or EndoD 1319:1379 The binding of ECA to PRG was also abolished in saliva cultures of mutants that expressed cell surface BgaA alone or together with either StrH or EndoD. 27316967 6 90 theme subsequent 1395:1404 arg1 loss 1406:1409 the subsequent loss 1391:1409 the subsequent loss of GNA binding 1391:1424 However, the subsequent loss of GNA binding was seen only in saliva cocultures of different mutants that together expressed all three cell surface GHs. 27316967 4 91 theme glycoproteins 1031:1043 arg1 masses 1002:1007 the apparent molecular masses 979:1007 the apparent molecular masses of basic proline-rich glycoproteins (PRG) 979:1049 The only notable change in the salivary proteome associated with this reduction of growth was a downward shift in the apparent molecular masses of basic proline-rich glycoproteins (PRG), which was accompanied by the loss of lectin binding sites for galactose-specific Erythrina cristagalli agglutinin (ECA) and mannose-specific Galanthus nivalis agglutinin (GNA). 27316967 9 92 used utilized 1932:1939 arg2 components 1904:1913 specific salivary components 1886:1913 specific salivary components 1886:1913 Little is known, however, about how specific salivary components are attacked and utilized by different members of the biofilm community, such as Streptococcus gordonii. 27316967 1 93 theme D 388:388 arg1 homologs 270:277 homologs 270:277 homologs of pneumococcal β-galactosidase (BgaA), β-N-acetylglucosaminidase (StrH), and endo-β-N-acetylglucosaminidase D (EndoD) 270:396 UNLABELLED The growth of the oral commensal Streptococcus gordonii in saliva may depend on a number of glycoside hydrolases (GHs), including three cell wall-anchored proteins that are homologs of pneumococcal β-galactosidase (BgaA), β-N-acetylglucosaminidase (StrH), and endo-β-N-acetylglucosaminidase D (EndoD). 27316967 1 93 theme D 388:388 arg1 proteins 252:259 three cell wall-anchored proteins 227:259 three cell wall-anchored proteins that are homologs of pneumococcal β-galactosidase (BgaA), β-N-acetylglucosaminidase (StrH), and endo-β-N-acetylglucosaminidase D (EndoD) 227:396 UNLABELLED The growth of the oral commensal Streptococcus gordonii in saliva may depend on a number of glycoside hydrolases (GHs), including three cell wall-anchored proteins that are homologs of pneumococcal β-galactosidase (BgaA), β-N-acetylglucosaminidase (StrH), and endo-β-N-acetylglucosaminidase D (EndoD). 27316967 1 94 theme hydrolases 199:208 arg1 number 179:184 a number 177:184 a number of glycoside hydrolases (GHs), including three cell wall-anchored proteins that are homologs of pneumococcal β-galactosidase (BgaA), β-N-acetylglucosaminidase (StrH), and endo-β-N-acetylglucosaminidase D (EndoD) 177:396 UNLABELLED The growth of the oral commensal Streptococcus gordonii in saliva may depend on a number of glycoside hydrolases (GHs), including three cell wall-anchored proteins that are homologs of pneumococcal β-galactosidase (BgaA), β-N-acetylglucosaminidase (StrH), and endo-β-N-acetylglucosaminidase D (EndoD). 27316967 1 94 theme hydrolases 199:208 arg1 proteins 252:259 three cell wall-anchored proteins 227:259 three cell wall-anchored proteins that are homologs of pneumococcal β-galactosidase (BgaA), β-N-acetylglucosaminidase (StrH), and endo-β-N-acetylglucosaminidase D (EndoD) 227:396 UNLABELLED The growth of the oral commensal Streptococcus gordonii in saliva may depend on a number of glycoside hydrolases (GHs), including three cell wall-anchored proteins that are homologs of pneumococcal β-galactosidase (BgaA), β-N-acetylglucosaminidase (StrH), and endo-β-N-acetylglucosaminidase D (EndoD). 27316967 10 95 theme Streptococcus 2020:2032 arg1 DL1 2043:2045 Streptococcus gordonii DL1 2020:2045 Streptococcus gordonii DL1 2020:2045 Streptococcus gordonii DL1 has three cell wall-anchored glycoside hydrolases that are predicted to act on host glycans. 27316967 3 96 theme DL1 733:735 arg1 growth 713:718 The overnight growth 699:718 The overnight growth of wild-type DL1 699:735 The overnight growth of wild-type DL1 was reduced 3- to 10-fold by the deletion of any one or two genes and approximately 20-fold by the deletion of all three genes. 27316967 8 97 theme salivary 1776:1783 arg1 glycoproteins 1785:1797 salivary glycoproteins 1776:1797 salivary glycoproteins 1776:1797 IMPORTANCE The ability of oral bacteria to grow on salivary glycoproteins is critical for dental plaque biofilm development. 27316967 6 98 theme different 1464:1472 arg1 mutants 1474:1480 different mutants 1464:1480 different mutants that together expressed all three cell surface GHs 1464:1531 However, the subsequent loss of GNA binding was seen only in saliva cocultures of different mutants that together expressed all three cell surface GHs. 27316967 12 99 theme significant 2477:2487 arg1 extent 2489:2494 a significant extent 2475:2494 a significant extent on sequential action of these cell surface GHs on N-linked glycans of basic proline-rich salivary glycoproteins, which appears to be an essential first step in salivary glycan foraging 2475:2679 The results indicate that the growth of S. gordonii DL1 depends to a significant extent on sequential action of these cell surface GHs on N-linked glycans of basic proline-rich salivary glycoproteins, which appears to be an essential first step in salivary glycan foraging. 27316967 11 100 theme glycan 2381:2386 arg1 foraging 2388:2395 glycan foraging 2381:2395 glycan foraging 2381:2395 In the present study, we introduced unmarked in-frame deletions in the corresponding genes, verified the presence (or absence) of encoded proteins on the resulting mutant strains, and compared these strains with wild-type DL1 for growth and glycan foraging in saliva. 27316967 4 101 theme lectin 1089:1094 arg1 sites 1104:1108 lectin binding sites 1089:1108 lectin binding sites for galactose-specific Erythrina cristagalli agglutinin (ECA) and mannose-specific Galanthus nivalis agglutinin (GNA) 1089:1226 The only notable change in the salivary proteome associated with this reduction of growth was a downward shift in the apparent molecular masses of basic proline-rich glycoproteins (PRG), which was accompanied by the loss of lectin binding sites for galactose-specific Erythrina cristagalli agglutinin (ECA) and mannose-specific Galanthus nivalis agglutinin (GNA). 27316967 10 102 theme glycoside 2076:2084 arg1 hydrolases 2086:2095 three cell wall-anchored glycoside hydrolases 2051:2095 three cell wall-anchored glycoside hydrolases that are predicted to act on host glycans 2051:2137 Streptococcus gordonii DL1 has three cell wall-anchored glycoside hydrolases that are predicted to act on host glycans. 27316967 1 103 theme commensal 120:128 arg1 gordonii 144:151 the oral commensal Streptococcus gordonii 111:151 the oral commensal Streptococcus gordonii 111:151 UNLABELLED The growth of the oral commensal Streptococcus gordonii in saliva may depend on a number of glycoside hydrolases (GHs), including three cell wall-anchored proteins that are homologs of pneumococcal β-galactosidase (BgaA), β-N-acetylglucosaminidase (StrH), and endo-β-N-acetylglucosaminidase D (EndoD). 27316967 7 104 theme gordonii 1578:1585 arg1 DL1 1587:1589 S. gordonii DL1 1575:1589 S. gordonii DL1 1575:1589 The findings indicate that the growth of S. gordonii DL1 in saliva depends to a significant extent on the sequential actions of first BgaA and then StrH and EndoD on N-linked glycans of PRG. 27316967 1 105 theme gordonii 144:151 arg1 growth 101:106 The growth 97:106 UNLABELLED The growth of the oral commensal Streptococcus gordonii in saliva 86:161 UNLABELLED The growth of the oral commensal Streptococcus gordonii in saliva may depend on a number of glycoside hydrolases (GHs), including three cell wall-anchored proteins that are homologs of pneumococcal β-galactosidase (BgaA), β-N-acetylglucosaminidase (StrH), and endo-β-N-acetylglucosaminidase D (EndoD). 27316967 2 106 theme corresponding 472:484 arg1 genes 486:490 the corresponding genes 468:490 the corresponding genes of S. gordonii DL1 468:509 In the present study, we introduced unmarked in-frame deletions into the corresponding genes of S. gordonii DL1, verified the presence (or absence) of the encoded proteins on the resulting mutant strains, and compared these strains with wild-type strain DL1 for growth and glycan foraging in saliva. 27316967 2 107 theme glycan 672:677 arg1 foraging 679:686 glycan foraging 672:686 glycan foraging 672:686 In the present study, we introduced unmarked in-frame deletions into the corresponding genes of S. gordonii DL1, verified the presence (or absence) of the encoded proteins on the resulting mutant strains, and compared these strains with wild-type strain DL1 for growth and glycan foraging in saliva. 27316967 12 108 theme essential 2632:2640 arg1 step 2648:2651 an essential first step 2629:2651 an essential first step in salivary glycan foraging 2629:2679 The results indicate that the growth of S. gordonii DL1 depends to a significant extent on sequential action of these cell surface GHs on N-linked glycans of basic proline-rich salivary glycoproteins, which appears to be an essential first step in salivary glycan foraging. 27316967 12 108 theme essential 2632:2640 arg1 glycoproteins 2594:2606 basic proline-rich salivary glycoproteins 2566:2606 basic proline-rich salivary glycoproteins 2566:2606 The results indicate that the growth of S. gordonii DL1 depends to a significant extent on sequential action of these cell surface GHs on N-linked glycans of basic proline-rich salivary glycoproteins, which appears to be an essential first step in salivary glycan foraging. 27316967 8 109 theme plaque 1822:1827 arg1 development 1837:1847 dental plaque biofilm development 1815:1847 dental plaque biofilm development 1815:1847 IMPORTANCE The ability of oral bacteria to grow on salivary glycoproteins is critical for dental plaque biofilm development. 27316967 11 110 theme resulting 2294:2302 arg1 strains 2311:2317 the resulting mutant strains 2290:2317 the resulting mutant strains 2290:2317 In the present study, we introduced unmarked in-frame deletions in the corresponding genes, verified the presence (or absence) of encoded proteins on the resulting mutant strains, and compared these strains with wild-type DL1 for growth and glycan foraging in saliva. 27316967 12 111 theme gordonii 2451:2458 arg1 DL1 2460:2462 S. gordonii DL1 2448:2462 S. gordonii DL1 2448:2462 The results indicate that the growth of S. gordonii DL1 depends to a significant extent on sequential action of these cell surface GHs on N-linked glycans of basic proline-rich salivary glycoproteins, which appears to be an essential first step in salivary glycan foraging. 27316967 4 112 theme cristagalli 1143:1153 arg1 ECA 1167:1169 ECA 1167:1169 ECA 1167:1169 The only notable change in the salivary proteome associated with this reduction of growth was a downward shift in the apparent molecular masses of basic proline-rich glycoproteins (PRG), which was accompanied by the loss of lectin binding sites for galactose-specific Erythrina cristagalli agglutinin (ECA) and mannose-specific Galanthus nivalis agglutinin (GNA). 27316967 4 112 theme cristagalli 1143:1153 arg1 agglutinin 1155:1164 galactose-specific Erythrina cristagalli agglutinin 1114:1164 galactose-specific Erythrina cristagalli agglutinin (ECA) 1114:1170 The only notable change in the salivary proteome associated with this reduction of growth was a downward shift in the apparent molecular masses of basic proline-rich glycoproteins (PRG), which was accompanied by the loss of lectin binding sites for galactose-specific Erythrina cristagalli agglutinin (ECA) and mannose-specific Galanthus nivalis agglutinin (GNA). 27316967 6 113 theme surface 1521:1527 arg1 GHs 1529:1531 all three cell surface GHs 1506:1531 all three cell surface GHs 1506:1531 However, the subsequent loss of GNA binding was seen only in saliva cocultures of different mutants that together expressed all three cell surface GHs. 27316967 3 114 theme genes 797:801 arg1 deletion 770:777 the deletion 766:777 the deletion of any one or two genes 766:801 The overnight growth of wild-type DL1 was reduced 3- to 10-fold by the deletion of any one or two genes and approximately 20-fold by the deletion of all three genes. 27316967 2 115 theme gordonii 498:505 arg1 DL1 507:509 S. gordonii DL1 495:509 S. gordonii DL1 495:509 In the present study, we introduced unmarked in-frame deletions into the corresponding genes of S. gordonii DL1, verified the presence (or absence) of the encoded proteins on the resulting mutant strains, and compared these strains with wild-type strain DL1 for growth and glycan foraging in saliva. 27316967 10 116 theme wall-anchored 2062:2074 arg1 hydrolases 2086:2095 three cell wall-anchored glycoside hydrolases 2051:2095 three cell wall-anchored glycoside hydrolases that are predicted to act on host glycans 2051:2137 Streptococcus gordonii DL1 has three cell wall-anchored glycoside hydrolases that are predicted to act on host glycans. 27316967 8 117 gly glycoproteins 1785:1797 arg1 glycoproteins 1785:1797 salivary glycoproteins 1776:1797 salivary glycoproteins 1776:1797 IMPORTANCE The ability of oral bacteria to grow on salivary glycoproteins is critical for dental plaque biofilm development. 27316967 12 118 from step 2648:2651 arg1 foraging 2672:2679 salivary glycan foraging 2656:2679 salivary glycan foraging 2656:2679 The results indicate that the growth of S. gordonii DL1 depends to a significant extent on sequential action of these cell surface GHs on N-linked glycans of basic proline-rich salivary glycoproteins, which appears to be an essential first step in salivary glycan foraging. 27316967 2 119 theme wild-type 636:644 arg1 DL1 653:655 wild-type strain DL1 636:655 wild-type strain DL1 for growth and glycan foraging in saliva 636:696 In the present study, we introduced unmarked in-frame deletions into the corresponding genes of S. gordonii DL1, verified the presence (or absence) of the encoded proteins on the resulting mutant strains, and compared these strains with wild-type strain DL1 for growth and glycan foraging in saliva. 27316967 5 120 theme ECA 1244:1246 arg1 binding 1233:1239 The binding 1229:1239 The binding of ECA to PRG 1229:1253 The binding of ECA to PRG was also abolished in saliva cultures of mutants that expressed cell surface BgaA alone or together with either StrH or EndoD. 27316967 4 121 theme notable 874:880 arg1 shift 970:974 a downward shift 959:974 a downward shift 959:974 The only notable change in the salivary proteome associated with this reduction of growth was a downward shift in the apparent molecular masses of basic proline-rich glycoproteins (PRG), which was accompanied by the loss of lectin binding sites for galactose-specific Erythrina cristagalli agglutinin (ECA) and mannose-specific Galanthus nivalis agglutinin (GNA). 27316967 4 121 theme notable 874:880 arg1 change 882:887 The only notable change 865:887 The only notable change in the salivary proteome associated with this reduction of growth 865:953 The only notable change in the salivary proteome associated with this reduction of growth was a downward shift in the apparent molecular masses of basic proline-rich glycoproteins (PRG), which was accompanied by the loss of lectin binding sites for galactose-specific Erythrina cristagalli agglutinin (ECA) and mannose-specific Galanthus nivalis agglutinin (GNA). 27316967 0 122 theme Surface 5:11 arg1 Hydrolases 23:32 Cell Surface Glycoside Hydrolases 0:32 Cell Surface Glycoside Hydrolases of Streptococcus gordonii 0:58 Cell Surface Glycoside Hydrolases of Streptococcus gordonii Promote Growth in Saliva. 27316967 4 123 gly glycoproteins 1031:1043 arg1 PRG 1046:1048 PRG 1046:1048 PRG 1046:1048 The only notable change in the salivary proteome associated with this reduction of growth was a downward shift in the apparent molecular masses of basic proline-rich glycoproteins (PRG), which was accompanied by the loss of lectin binding sites for galactose-specific Erythrina cristagalli agglutinin (ECA) and mannose-specific Galanthus nivalis agglutinin (GNA). 27316967 4 123 gly glycoproteins 1031:1043 arg1 glycoproteins 1031:1043 basic proline-rich glycoproteins 1012:1043 basic proline-rich glycoproteins (PRG) 1012:1049 The only notable change in the salivary proteome associated with this reduction of growth was a downward shift in the apparent molecular masses of basic proline-rich glycoproteins (PRG), which was accompanied by the loss of lectin binding sites for galactose-specific Erythrina cristagalli agglutinin (ECA) and mannose-specific Galanthus nivalis agglutinin (GNA). 27316967 12 124 gly glycoproteins 2594:2606 arg1 step 2648:2651 an essential first step 2629:2651 an essential first step in salivary glycan foraging 2629:2679 The results indicate that the growth of S. gordonii DL1 depends to a significant extent on sequential action of these cell surface GHs on N-linked glycans of basic proline-rich salivary glycoproteins, which appears to be an essential first step in salivary glycan foraging. 27316967 12 124 gly glycoproteins 2594:2606 arg1 glycoproteins 2594:2606 basic proline-rich salivary glycoproteins 2566:2606 basic proline-rich salivary glycoproteins 2566:2606 The results indicate that the growth of S. gordonii DL1 depends to a significant extent on sequential action of these cell surface GHs on N-linked glycans of basic proline-rich salivary glycoproteins, which appears to be an essential first step in salivary glycan foraging. 27316967 1 125 theme UNLABELLED 86:95 arg1 growth 101:106 The growth 97:106 UNLABELLED The growth of the oral commensal Streptococcus gordonii in saliva 86:161 UNLABELLED The growth of the oral commensal Streptococcus gordonii in saliva may depend on a number of glycoside hydrolases (GHs), including three cell wall-anchored proteins that are homologs of pneumococcal β-galactosidase (BgaA), β-N-acetylglucosaminidase (StrH), and endo-β-N-acetylglucosaminidase D (EndoD). 27316967 4 126 theme galactose-specific 1114:1131 arg1 ECA 1167:1169 ECA 1167:1169 ECA 1167:1169 The only notable change in the salivary proteome associated with this reduction of growth was a downward shift in the apparent molecular masses of basic proline-rich glycoproteins (PRG), which was accompanied by the loss of lectin binding sites for galactose-specific Erythrina cristagalli agglutinin (ECA) and mannose-specific Galanthus nivalis agglutinin (GNA). 27316967 4 126 theme galactose-specific 1114:1131 arg1 agglutinin 1155:1164 galactose-specific Erythrina cristagalli agglutinin 1114:1164 galactose-specific Erythrina cristagalli agglutinin (ECA) 1114:1170 The only notable change in the salivary proteome associated with this reduction of growth was a downward shift in the apparent molecular masses of basic proline-rich glycoproteins (PRG), which was accompanied by the loss of lectin binding sites for galactose-specific Erythrina cristagalli agglutinin (ECA) and mannose-specific Galanthus nivalis agglutinin (GNA). 27316967 12 127 link N-linked 2546:2553 arg1 glycans 2555:2561 N-linked glycans 2546:2561 N-linked glycans of basic proline-rich salivary glycoproteins, which appears to be an essential first step in salivary glycan foraging 2546:2679 The results indicate that the growth of S. gordonii DL1 depends to a significant extent on sequential action of these cell surface GHs on N-linked glycans of basic proline-rich salivary glycoproteins, which appears to be an essential first step in salivary glycan foraging. 27316967 11 128 theme corresponding 2211:2223 arg1 genes 2225:2229 the corresponding genes 2207:2229 the corresponding genes 2207:2229 In the present study, we introduced unmarked in-frame deletions in the corresponding genes, verified the presence (or absence) of encoded proteins on the resulting mutant strains, and compared these strains with wild-type DL1 for growth and glycan foraging in saliva. 27316967 3 129 theme genes 858:862 arg1 deletion 836:843 the deletion 832:843 the deletion of all three genes 832:862 The overnight growth of wild-type DL1 was reduced 3- to 10-fold by the deletion of any one or two genes and approximately 20-fold by the deletion of all three genes. 27316967 4 130 theme growth 948:953 arg1 reduction 935:943 this reduction 930:943 this reduction of growth 930:953 The only notable change in the salivary proteome associated with this reduction of growth was a downward shift in the apparent molecular masses of basic proline-rich glycoproteins (PRG), which was accompanied by the loss of lectin binding sites for galactose-specific Erythrina cristagalli agglutinin (ECA) and mannose-specific Galanthus nivalis agglutinin (GNA). 27316967 4 131 theme nivalis 1203:1209 arg1 GNA 1223:1225 GNA 1223:1225 GNA 1223:1225 The only notable change in the salivary proteome associated with this reduction of growth was a downward shift in the apparent molecular masses of basic proline-rich glycoproteins (PRG), which was accompanied by the loss of lectin binding sites for galactose-specific Erythrina cristagalli agglutinin (ECA) and mannose-specific Galanthus nivalis agglutinin (GNA). 27316967 4 131 theme nivalis 1203:1209 arg1 agglutinin 1211:1220 mannose-specific Galanthus nivalis agglutinin 1176:1220 mannose-specific Galanthus nivalis agglutinin (GNA) 1176:1226 The only notable change in the salivary proteome associated with this reduction of growth was a downward shift in the apparent molecular masses of basic proline-rich glycoproteins (PRG), which was accompanied by the loss of lectin binding sites for galactose-specific Erythrina cristagalli agglutinin (ECA) and mannose-specific Galanthus nivalis agglutinin (GNA). 27316967 11 132 from absence 2258:2264 arg1 strains 2311:2317 the resulting mutant strains 2290:2317 the resulting mutant strains 2290:2317 In the present study, we introduced unmarked in-frame deletions in the corresponding genes, verified the presence (or absence) of encoded proteins on the resulting mutant strains, and compared these strains with wild-type DL1 for growth and glycan foraging in saliva. 27316967 0 133 theme Streptococcus 37:49 arg1 gordonii 51:58 Streptococcus gordonii 37:58 Streptococcus gordonii 37:58 Cell Surface Glycoside Hydrolases of Streptococcus gordonii Promote Growth in Saliva. 27316967 12 134 from action 2510:2515 arg1 glycans 2555:2561 N-linked glycans 2546:2561 N-linked glycans of basic proline-rich salivary glycoproteins, which appears to be an essential first step in salivary glycan foraging 2546:2679 The results indicate that the growth of S. gordonii DL1 depends to a significant extent on sequential action of these cell surface GHs on N-linked glycans of basic proline-rich salivary glycoproteins, which appears to be an essential first step in salivary glycan foraging. 27316967 2 135 theme in-frame 444:451 arg1 deletions 453:461 unmarked in-frame deletions 435:461 unmarked in-frame deletions 435:461 In the present study, we introduced unmarked in-frame deletions into the corresponding genes of S. gordonii DL1, verified the presence (or absence) of the encoded proteins on the resulting mutant strains, and compared these strains with wild-type strain DL1 for growth and glycan foraging in saliva. 27316967 1 136 theme β-galactosidase 295:309 arg1 homologs 270:277 homologs 270:277 homologs of pneumococcal β-galactosidase (BgaA), β-N-acetylglucosaminidase (StrH), and endo-β-N-acetylglucosaminidase D (EndoD) 270:396 UNLABELLED The growth of the oral commensal Streptococcus gordonii in saliva may depend on a number of glycoside hydrolases (GHs), including three cell wall-anchored proteins that are homologs of pneumococcal β-galactosidase (BgaA), β-N-acetylglucosaminidase (StrH), and endo-β-N-acetylglucosaminidase D (EndoD). 27316967 1 136 theme β-galactosidase 295:309 arg1 proteins 252:259 three cell wall-anchored proteins 227:259 three cell wall-anchored proteins that are homologs of pneumococcal β-galactosidase (BgaA), β-N-acetylglucosaminidase (StrH), and endo-β-N-acetylglucosaminidase D (EndoD) 227:396 UNLABELLED The growth of the oral commensal Streptococcus gordonii in saliva may depend on a number of glycoside hydrolases (GHs), including three cell wall-anchored proteins that are homologs of pneumococcal β-galactosidase (BgaA), β-N-acetylglucosaminidase (StrH), and endo-β-N-acetylglucosaminidase D (EndoD). 27316967 7 137 theme PRG 1720:1722 arg1 glycans 1709:1715 N-linked glycans 1700:1715 N-linked glycans of PRG 1700:1722 The findings indicate that the growth of S. gordonii DL1 in saliva depends to a significant extent on the sequential actions of first BgaA and then StrH and EndoD on N-linked glycans of PRG. 27316967 7 138 theme N-linked 1700:1707 arg1 glycans 1709:1715 N-linked glycans 1700:1715 N-linked glycans of PRG 1700:1722 The findings indicate that the growth of S. gordonii DL1 in saliva depends to a significant extent on the sequential actions of first BgaA and then StrH and EndoD on N-linked glycans of PRG. 27316967 1 139 from growth 101:106 arg1 saliva 156:161 saliva 156:161 saliva 156:161 UNLABELLED The growth of the oral commensal Streptococcus gordonii in saliva may depend on a number of glycoside hydrolases (GHs), including three cell wall-anchored proteins that are homologs of pneumococcal β-galactosidase (BgaA), β-N-acetylglucosaminidase (StrH), and endo-β-N-acetylglucosaminidase D (EndoD). 27316967 7 140 link N-linked 1700:1707 arg1 glycans 1709:1715 N-linked glycans 1700:1715 N-linked glycans of PRG 1700:1722 The findings indicate that the growth of S. gordonii DL1 in saliva depends to a significant extent on the sequential actions of first BgaA and then StrH and EndoD on N-linked glycans of PRG. 27316967 4 141 theme sites 1104:1108 arg1 loss 1081:1084 the loss 1077:1084 the loss of lectin binding sites for galactose-specific Erythrina cristagalli agglutinin (ECA) and mannose-specific Galanthus nivalis agglutinin (GNA) 1077:1226 The only notable change in the salivary proteome associated with this reduction of growth was a downward shift in the apparent molecular masses of basic proline-rich glycoproteins (PRG), which was accompanied by the loss of lectin binding sites for galactose-specific Erythrina cristagalli agglutinin (ECA) and mannose-specific Galanthus nivalis agglutinin (GNA). 27316967 7 142 theme EndoD 1691:1695 arg1 actions 1651:1657 the sequential actions 1636:1657 the sequential actions of first BgaA and then StrH and EndoD on N-linked glycans of PRG 1636:1722 The findings indicate that the growth of S. gordonii DL1 in saliva depends to a significant extent on the sequential actions of first BgaA and then StrH and EndoD on N-linked glycans of PRG. 27316967 4 143 theme mannose-specific 1176:1191 arg1 GNA 1223:1225 GNA 1223:1225 GNA 1223:1225 The only notable change in the salivary proteome associated with this reduction of growth was a downward shift in the apparent molecular masses of basic proline-rich glycoproteins (PRG), which was accompanied by the loss of lectin binding sites for galactose-specific Erythrina cristagalli agglutinin (ECA) and mannose-specific Galanthus nivalis agglutinin (GNA). 27316967 4 143 theme mannose-specific 1176:1191 arg1 agglutinin 1211:1220 mannose-specific Galanthus nivalis agglutinin 1176:1220 mannose-specific Galanthus nivalis agglutinin (GNA) 1176:1226 The only notable change in the salivary proteome associated with this reduction of growth was a downward shift in the apparent molecular masses of basic proline-rich glycoproteins (PRG), which was accompanied by the loss of lectin binding sites for galactose-specific Erythrina cristagalli agglutinin (ECA) and mannose-specific Galanthus nivalis agglutinin (GNA). 27316967 7 144 theme StrH 1682:1685 arg1 actions 1651:1657 the sequential actions 1636:1657 the sequential actions of first BgaA and then StrH and EndoD on N-linked glycans of PRG 1636:1722 The findings indicate that the growth of S. gordonii DL1 in saliva depends to a significant extent on the sequential actions of first BgaA and then StrH and EndoD on N-linked glycans of PRG. 27316967 4 145 theme molecular 992:1000 arg1 masses 1002:1007 the apparent molecular masses 979:1007 the apparent molecular masses of basic proline-rich glycoproteins (PRG) 979:1049 The only notable change in the salivary proteome associated with this reduction of growth was a downward shift in the apparent molecular masses of basic proline-rich glycoproteins (PRG), which was accompanied by the loss of lectin binding sites for galactose-specific Erythrina cristagalli agglutinin (ECA) and mannose-specific Galanthus nivalis agglutinin (GNA). 27316967 4 146 from change 882:887 arg1 proteome 905:912 the salivary proteome 892:912 the salivary proteome associated with this reduction of growth 892:953 The only notable change in the salivary proteome associated with this reduction of growth was a downward shift in the apparent molecular masses of basic proline-rich glycoproteins (PRG), which was accompanied by the loss of lectin binding sites for galactose-specific Erythrina cristagalli agglutinin (ECA) and mannose-specific Galanthus nivalis agglutinin (GNA). 27084007 18 0 theme mass 2795:2798 arg1 spectrometry 2800:2811 advanced mass spectrometry 2786:2811 advanced mass spectrometry (nano-liquid chromatography chip-quadrupole time of flight mass spectrometry [nano-LC-Chip-Q-TOF MS]) 2786:2913 The selectivity of consumption of individual N-glycans was determined using advanced mass spectrometry (nano-liquid chromatography chip-quadrupole time of flight mass spectrometry [nano-LC-Chip-Q-TOF MS]) to reveal that B. infantis can consume the range of glycan structures released from whey protein concentrate. 27084007 1 1 theme members 268:274 arg1 enrichment 250:259 a specific enrichment 239:259 a specific enrichment of key members of the gut microbiota in the nursing infant, a consortium known as the milk-oriented microbiome 239:370 UNLABELLED Milk, in addition to nourishing the neonate, provides a range of complex glycans whose construction ensures a specific enrichment of key members of the gut microbiota in the nursing infant, a consortium known as the milk-oriented microbiome. 27084007 6 2 theme rapid 969:973 arg1 growth 975:980 the rapid growth 965:980 the rapid growth of Bifidobacterium longum subsp 965:1012 EndoBI-1-released N-glycans supported the rapid growth of Bifidobacterium longum subsp. 27084007 0 3 attach Released 17:24 arg2 Oligosaccharides 0:15 Oligosaccharides 0:15 Oligosaccharides Released from Milk Glycoproteins 0:48 Oligosaccharides Released from Milk Glycoproteins Are Selective Growth Substrates for Infant-Associated Bifidobacteria. 27084007 0 3 attach Released 17:24 arg1 Glycoproteins 36:48 Milk Glycoproteins 31:48 Milk Glycoproteins 31:48 Oligosaccharides Released from Milk Glycoproteins Are Selective Growth Substrates for Infant-Associated Bifidobacteria. 27084007 10 4 theme Mass 1405:1408 arg1 profiling 1429:1437 Mass spectrometry-based profiling 1405:1437 Mass spectrometry-based profiling 1405:1437 Mass spectrometry-based profiling revealed that B. infantis consumed 73% of neutral and 92% of sialylated N-glycans, while B. lactis degraded only 11% of neutral and virtually no (<1%) sialylated N-glycans. 27084007 13 5 theme milk 2199:2202 arg1 oligosaccharides 2204:2219 human milk oligosaccharides 2193:2219 human milk oligosaccharides 2193:2219 Finally, the variety of N-glycans released from bovine milk glycoproteins suggests that they may serve as novel prebiotic substrates with selective properties similar to those of human milk oligosaccharides. 27084007 11 6 link N-linked 1659:1666 arg1 glycoproteins 1668:1680 N-linked glycoproteins 1659:1680 N-linked glycoproteins from milk 1659:1690 These results provide mechanistic support that N-linked glycoproteins from milk serve as selective substrates for the enrichment of infant-associated bifidobacteria capable of carrying out the initial deglycosylation. 27084007 11 6 link N-linked 1659:1666 arg1 substrates 1711:1720 selective substrates 1701:1720 selective substrates for the enrichment of infant-associated bifidobacteria capable of carrying out the initial deglycosylation 1701:1827 These results provide mechanistic support that N-linked glycoproteins from milk serve as selective substrates for the enrichment of infant-associated bifidobacteria capable of carrying out the initial deglycosylation. 27084007 18 7 attach released 2985:2992 arg1 concentrate 3012:3022 whey protein concentrate 2999:3022 whey protein concentrate 2999:3022 The selectivity of consumption of individual N-glycans was determined using advanced mass spectrometry (nano-liquid chromatography chip-quadrupole time of flight mass spectrometry [nano-LC-Chip-Q-TOF MS]) to reveal that B. infantis can consume the range of glycan structures released from whey protein concentrate. 27084007 18 7 attach released 2985:2992 arg2 structures 2974:2983 glycan structures 2967:2983 glycan structures released from whey protein concentrate 2967:3022 The selectivity of consumption of individual N-glycans was determined using advanced mass spectrometry (nano-liquid chromatography chip-quadrupole time of flight mass spectrometry [nano-LC-Chip-Q-TOF MS]) to reveal that B. infantis can consume the range of glycan structures released from whey protein concentrate. 27084007 10 8 theme neutral 1559:1565 arg1 N-glycans 1601:1609 neutral and virtually no (<1%) sialylated N-glycans 1559:1609 neutral and virtually no (<1%) sialylated N-glycans 1559:1609 Mass spectrometry-based profiling revealed that B. infantis consumed 73% of neutral and 92% of sialylated N-glycans, while B. lactis degraded only 11% of neutral and virtually no (<1%) sialylated N-glycans. 27084007 7 9 theme subsp 1152:1156 arg1 growth 1117:1122 growth 1117:1122 growth of Bifidobacterium animalis subsp 1117:1156 infantis (B. infantis), a species that grows well on human milk oligosaccharides, but did not support growth of Bifidobacterium animalis subsp. 27084007 9 10 theme infantis 1220:1227 arg1 15697 1234:1238 B. infantis ATCC 15697 1217:1238 B. infantis ATCC 15697 1217:1238 Conversely, B. infantis ATCC 15697 did not grow on the deglycosylated milk protein fraction, clearly demonstrating that the glycan portion of milk glycoproteins provided the key substrate for growth. 27084007 3 11 located found 588:592 arg2 EndoBI-1 578:585 EndoBI-1 578:585 EndoBI-1 578:585 Recently, a cell wall-associated endo-β-N-acetylglucosaminidase (EndoBI-1) found in various infant-borne bifidobacteria was shown to remove a range of intact N-linked glycans. 27084007 3 11 located found 588:592 arg1 bifidobacteria 618:631 various infant-borne bifidobacteria 597:631 various infant-borne bifidobacteria 597:631 Recently, a cell wall-associated endo-β-N-acetylglucosaminidase (EndoBI-1) found in various infant-borne bifidobacteria was shown to remove a range of intact N-linked glycans. 27084007 3 11 located found 588:592 arg2 endo-β-N-acetylglucosaminidase 546:575 a cell wall-associated endo-β-N-acetylglucosaminidase 523:575 a cell wall-associated endo-β-N-acetylglucosaminidase (EndoBI-1) found in various infant-borne bifidobacteria 523:631 Recently, a cell wall-associated endo-β-N-acetylglucosaminidase (EndoBI-1) found in various infant-borne bifidobacteria was shown to remove a range of intact N-linked glycans. 27084007 5 12 theme pilot 914:918 arg1 scale 920:924 the pilot scale 910:924 the pilot scale 910:924 We demonstrated that EndoBI-1 released N-glycans from concentrated bovine colostrum at the pilot scale. 27084007 12 13 theme glycoproteins 1999:2011 arg1 consumption 1984:1994 consumption 1984:1994 consumption of glycoproteins 1984:2011 Moreover, released N-glycans were better growth substrates than the intact milk glycoproteins, suggesting that EndoBI-1 cleavage is a key initial step in consumption of glycoproteins. 27084007 6 14 theme EndoBI-1-released 927:943 arg1 N-glycans 945:953 EndoBI-1-released N-glycans 927:953 EndoBI-1-released N-glycans 927:953 EndoBI-1-released N-glycans supported the rapid growth of Bifidobacterium longum subsp. 27084007 1 15 theme gut 283:285 arg1 microbiota 287:296 the gut microbiota 279:296 the gut microbiota 279:296 UNLABELLED Milk, in addition to nourishing the neonate, provides a range of complex glycans whose construction ensures a specific enrichment of key members of the gut microbiota in the nursing infant, a consortium known as the milk-oriented microbiome. 27084007 7 16 theme Bifidobacterium 1127:1141 arg1 subsp 1152:1156 Bifidobacterium animalis subsp 1127:1156 Bifidobacterium animalis subsp 1127:1156 infantis (B. infantis), a species that grows well on human milk oligosaccharides, but did not support growth of Bifidobacterium animalis subsp. 27084007 3 17 theme various 597:603 arg1 bifidobacteria 618:631 various infant-borne bifidobacteria 597:631 various infant-borne bifidobacteria 597:631 Recently, a cell wall-associated endo-β-N-acetylglucosaminidase (EndoBI-1) found in various infant-borne bifidobacteria was shown to remove a range of intact N-linked glycans. 27084007 1 18 theme complex 196:202 arg1 glycans 204:210 complex glycans 196:210 complex glycans 196:210 UNLABELLED Milk, in addition to nourishing the neonate, provides a range of complex glycans whose construction ensures a specific enrichment of key members of the gut microbiota in the nursing infant, a consortium known as the milk-oriented microbiome. 27084007 11 19 theme initial 1805:1811 arg1 deglycosylation 1813:1827 the initial deglycosylation 1801:1827 the initial deglycosylation 1801:1827 These results provide mechanistic support that N-linked glycoproteins from milk serve as selective substrates for the enrichment of infant-associated bifidobacteria capable of carrying out the initial deglycosylation. 27084007 13 20 theme selective 2152:2160 arg1 properties 2162:2171 selective properties 2152:2171 selective properties similar to those of human milk oligosaccharides 2152:2219 Finally, the variety of N-glycans released from bovine milk glycoproteins suggests that they may serve as novel prebiotic substrates with selective properties similar to those of human milk oligosaccharides. 27084007 5 21 theme bovine 890:895 arg1 colostrum 897:905 concentrated bovine colostrum 877:905 concentrated bovine colostrum 877:905 We demonstrated that EndoBI-1 released N-glycans from concentrated bovine colostrum at the pilot scale. 27084007 10 22 gly sialylated 1500:1509 arg1 N-glycans 1511:1519 sialylated N-glycans 1500:1519 sialylated N-glycans 1500:1519 Mass spectrometry-based profiling revealed that B. infantis consumed 73% of neutral and 92% of sialylated N-glycans, while B. lactis degraded only 11% of neutral and virtually no (<1%) sialylated N-glycans. 27084007 13 23 theme novel 2120:2124 arg1 substrates 2136:2145 novel prebiotic substrates 2120:2145 novel prebiotic substrates with selective properties similar to those of human milk oligosaccharides 2120:2219 Finally, the variety of N-glycans released from bovine milk glycoproteins suggests that they may serve as novel prebiotic substrates with selective properties similar to those of human milk oligosaccharides. 27084007 13 23 theme novel 2120:2124 arg1 they 2102:2105 they 2102:2105 they 2102:2105 Finally, the variety of N-glycans released from bovine milk glycoproteins suggests that they may serve as novel prebiotic substrates with selective properties similar to those of human milk oligosaccharides. 27084007 15 24 theme glycoprotein 2353:2364 arg1 part 2343:2346 part 2343:2346 part of a glycoprotein (glycans or polypeptides) 2343:2390 However, which part of a glycoprotein (glycans or polypeptides) is responsible for this function was not known. 27084007 13 25 theme similar 2173:2179 arg1 properties 2162:2171 selective properties 2152:2171 selective properties similar to those of human milk oligosaccharides 2152:2219 Finally, the variety of N-glycans released from bovine milk glycoproteins suggests that they may serve as novel prebiotic substrates with selective properties similar to those of human milk oligosaccharides. 27084007 17 26 theme infant 2690:2695 arg1 growth 2652:2657 the growth 2648:2657 the growth 2648:2657 The results showed that the glycans selectively stimulated the growth of B. infantis, which is a key infant gut microbe. 27084007 17 26 theme infant 2690:2695 arg1 microbe 2701:2707 a key infant gut microbe 2684:2707 a key infant gut microbe 2684:2707 The results showed that the glycans selectively stimulated the growth of B. infantis, which is a key infant gut microbe. 27084007 1 27 theme microbiota 287:296 arg1 members 268:274 key members 264:274 key members of the gut microbiota 264:296 UNLABELLED Milk, in addition to nourishing the neonate, provides a range of complex glycans whose construction ensures a specific enrichment of key members of the gut microbiota in the nursing infant, a consortium known as the milk-oriented microbiome. 27084007 10 28 theme sialylated 1590:1599 arg1 N-glycans 1601:1609 neutral and virtually no (<1%) sialylated N-glycans 1559:1609 neutral and virtually no (<1%) sialylated N-glycans 1559:1609 Mass spectrometry-based profiling revealed that B. infantis consumed 73% of neutral and 92% of sialylated N-glycans, while B. lactis degraded only 11% of neutral and virtually no (<1%) sialylated N-glycans. 27084007 9 29 theme deglycosylated 1260:1273 arg1 fraction 1288:1295 the deglycosylated milk protein fraction 1256:1295 the deglycosylated milk protein fraction 1256:1295 Conversely, B. infantis ATCC 15697 did not grow on the deglycosylated milk protein fraction, clearly demonstrating that the glycan portion of milk glycoproteins provided the key substrate for growth. 27084007 13 30 theme prebiotic 2126:2134 arg1 substrates 2136:2145 novel prebiotic substrates 2120:2145 novel prebiotic substrates with selective properties similar to those of human milk oligosaccharides 2120:2219 Finally, the variety of N-glycans released from bovine milk glycoproteins suggests that they may serve as novel prebiotic substrates with selective properties similar to those of human milk oligosaccharides. 27084007 13 30 theme prebiotic 2126:2134 arg1 they 2102:2105 they 2102:2105 they 2102:2105 Finally, the variety of N-glycans released from bovine milk glycoproteins suggests that they may serve as novel prebiotic substrates with selective properties similar to those of human milk oligosaccharides. 27084007 6 31 theme longum 1001:1006 arg1 subsp 1008:1012 Bifidobacterium longum subsp 985:1012 Bifidobacterium longum subsp 985:1012 EndoBI-1-released N-glycans supported the rapid growth of Bifidobacterium longum subsp. 27084007 12 32 gly glycoproteins 1999:2011 arg1 glycoproteins 1999:2011 glycoproteins 1999:2011 glycoproteins 1999:2011 Moreover, released N-glycans were better growth substrates than the intact milk glycoproteins, suggesting that EndoBI-1 cleavage is a key initial step in consumption of glycoproteins. 27084007 16 33 gly glycoproteins 2519:2531 arg1 glycoproteins 2519:2531 milk glycoproteins 2514:2531 milk glycoproteins 2514:2531 In this study, we used a novel enzyme to cleave conjugated N-glycans from milk glycoproteins and tested their consumption by various bifidobacteria. 27084007 11 34 theme bifidobacteria 1762:1775 arg1 enrichment 1730:1739 the enrichment 1726:1739 the enrichment of infant-associated bifidobacteria capable of carrying out the initial deglycosylation 1726:1827 These results provide mechanistic support that N-linked glycoproteins from milk serve as selective substrates for the enrichment of infant-associated bifidobacteria capable of carrying out the initial deglycosylation. 27084007 9 35 theme protein 1280:1286 arg1 fraction 1288:1295 the deglycosylated milk protein fraction 1256:1295 the deglycosylated milk protein fraction 1256:1295 Conversely, B. infantis ATCC 15697 did not grow on the deglycosylated milk protein fraction, clearly demonstrating that the glycan portion of milk glycoproteins provided the key substrate for growth. 27084007 4 36 theme released 716:723 arg1 structures 741:750 these released oligosaccharide structures 710:750 these released oligosaccharide structures 710:750 We hypothesized that these released oligosaccharide structures can serve as a sole source for the selective growth of bifidobacteria. 27084007 4 36 theme released 716:723 arg1 source 772:777 a sole source 765:777 a sole source for the selective growth of bifidobacteria 765:820 We hypothesized that these released oligosaccharide structures can serve as a sole source for the selective growth of bifidobacteria. 27084007 2 37 theme infant 501:506 arg1 gut 508:510 the breast-fed infant gut 486:510 the breast-fed infant gut 486:510 Milk glycoproteins are thought to function similarly, as specific growth substrates for bifidobacteria common to the breast-fed infant gut. 27084007 18 38 theme N-glycans 2755:2763 arg1 consumption 2729:2739 consumption 2729:2739 consumption of individual N-glycans 2729:2763 The selectivity of consumption of individual N-glycans was determined using advanced mass spectrometry (nano-liquid chromatography chip-quadrupole time of flight mass spectrometry [nano-LC-Chip-Q-TOF MS]) to reveal that B. infantis can consume the range of glycan structures released from whey protein concentrate. 27084007 0 39 theme Infant-Associated 86:102 arg1 Bifidobacteria 104:117 Infant-Associated Bifidobacteria 86:117 Infant-Associated Bifidobacteria 86:117 Oligosaccharides Released from Milk Glycoproteins Are Selective Growth Substrates for Infant-Associated Bifidobacteria. 27084007 18 40 theme structures 2974:2983 arg1 range 2958:2962 the range 2954:2962 the range of glycan structures released from whey protein concentrate 2954:3022 The selectivity of consumption of individual N-glycans was determined using advanced mass spectrometry (nano-liquid chromatography chip-quadrupole time of flight mass spectrometry [nano-LC-Chip-Q-TOF MS]) to reveal that B. infantis can consume the range of glycan structures released from whey protein concentrate. 27084007 11 41 from milk 1687:1690 arg1 glycoproteins 1668:1680 N-linked glycoproteins 1659:1680 N-linked glycoproteins from milk 1659:1690 These results provide mechanistic support that N-linked glycoproteins from milk serve as selective substrates for the enrichment of infant-associated bifidobacteria capable of carrying out the initial deglycosylation. 27084007 11 41 from milk 1687:1690 arg1 substrates 1711:1720 selective substrates 1701:1720 selective substrates for the enrichment of infant-associated bifidobacteria capable of carrying out the initial deglycosylation 1701:1827 These results provide mechanistic support that N-linked glycoproteins from milk serve as selective substrates for the enrichment of infant-associated bifidobacteria capable of carrying out the initial deglycosylation. 27084007 9 42 gly glycoproteins 1352:1364 arg1 glycoproteins 1352:1364 milk glycoproteins 1347:1364 milk glycoproteins 1347:1364 Conversely, B. infantis ATCC 15697 did not grow on the deglycosylated milk protein fraction, clearly demonstrating that the glycan portion of milk glycoproteins provided the key substrate for growth. 27084007 7 43 dep infantis 1015:1022 arg1 infantis 1028:1035 B. infantis 1025:1035 B. infantis 1025:1035 infantis (B. infantis), a species that grows well on human milk oligosaccharides, but did not support growth of Bifidobacterium animalis subsp. 27084007 1 44 theme milk-oriented 347:359 arg1 microbiome 361:370 the milk-oriented microbiome 343:370 the milk-oriented microbiome 343:370 UNLABELLED Milk, in addition to nourishing the neonate, provides a range of complex glycans whose construction ensures a specific enrichment of key members of the gut microbiota in the nursing infant, a consortium known as the milk-oriented microbiome. 27084007 13 45 with substrates 2136:2145 arg1 properties 2162:2171 selective properties 2152:2171 selective properties similar to those of human milk oligosaccharides 2152:2219 Finally, the variety of N-glycans released from bovine milk glycoproteins suggests that they may serve as novel prebiotic substrates with selective properties similar to those of human milk oligosaccharides. 27084007 16 46 used used 2458:2461 arg2 we 2455:2456 we 2455:2456 we 2455:2456 In this study, we used a novel enzyme to cleave conjugated N-glycans from milk glycoproteins and tested their consumption by various bifidobacteria. 27084007 4 47 theme bifidobacteria 807:820 arg1 growth 797:802 the selective growth 783:802 the selective growth of bifidobacteria 783:820 We hypothesized that these released oligosaccharide structures can serve as a sole source for the selective growth of bifidobacteria. 27084007 2 48 gly glycoproteins 378:390 arg1 substrates 446:455 specific growth substrates 430:455 specific growth substrates for bifidobacteria common to the breast-fed infant gut 430:510 Milk glycoproteins are thought to function similarly, as specific growth substrates for bifidobacteria common to the breast-fed infant gut. 27084007 2 48 gly glycoproteins 378:390 arg1 glycoproteins 378:390 Milk glycoproteins 373:390 Milk glycoproteins 373:390 Milk glycoproteins are thought to function similarly, as specific growth substrates for bifidobacteria common to the breast-fed infant gut. 27084007 12 49 gly glycoproteins 1910:1922 arg1 glycoproteins 1910:1922 the intact milk glycoproteins 1894:1922 the intact milk glycoproteins 1894:1922 Moreover, released N-glycans were better growth substrates than the intact milk glycoproteins, suggesting that EndoBI-1 cleavage is a key initial step in consumption of glycoproteins. 27084007 9 50 theme milk 1347:1350 arg1 glycoproteins 1352:1364 milk glycoproteins 1347:1364 milk glycoproteins 1347:1364 Conversely, B. infantis ATCC 15697 did not grow on the deglycosylated milk protein fraction, clearly demonstrating that the glycan portion of milk glycoproteins provided the key substrate for growth. 27084007 1 51 theme UNLABELLED 120:129 arg1 Milk 131:134 UNLABELLED Milk 120:134 UNLABELLED Milk 120:134 UNLABELLED Milk, in addition to nourishing the neonate, provides a range of complex glycans whose construction ensures a specific enrichment of key members of the gut microbiota in the nursing infant, a consortium known as the milk-oriented microbiome. 27084007 11 52 theme selective 1701:1709 arg1 glycoproteins 1668:1680 N-linked glycoproteins 1659:1680 N-linked glycoproteins from milk 1659:1690 These results provide mechanistic support that N-linked glycoproteins from milk serve as selective substrates for the enrichment of infant-associated bifidobacteria capable of carrying out the initial deglycosylation. 27084007 11 52 theme selective 1701:1709 arg1 substrates 1711:1720 selective substrates 1701:1720 selective substrates for the enrichment of infant-associated bifidobacteria capable of carrying out the initial deglycosylation 1701:1827 These results provide mechanistic support that N-linked glycoproteins from milk serve as selective substrates for the enrichment of infant-associated bifidobacteria capable of carrying out the initial deglycosylation. 27084007 2 53 theme growth 439:444 arg1 substrates 446:455 specific growth substrates 430:455 specific growth substrates for bifidobacteria common to the breast-fed infant gut 430:510 Milk glycoproteins are thought to function similarly, as specific growth substrates for bifidobacteria common to the breast-fed infant gut. 27084007 2 53 theme growth 439:444 arg1 glycoproteins 378:390 Milk glycoproteins 373:390 Milk glycoproteins 373:390 Milk glycoproteins are thought to function similarly, as specific growth substrates for bifidobacteria common to the breast-fed infant gut. 27084007 13 54 gly glycoproteins 2074:2086 arg1 glycoproteins 2074:2086 bovine milk glycoproteins 2062:2086 bovine milk glycoproteins 2062:2086 Finally, the variety of N-glycans released from bovine milk glycoproteins suggests that they may serve as novel prebiotic substrates with selective properties similar to those of human milk oligosaccharides. 27084007 10 55 theme sialylated 1500:1509 arg1 N-glycans 1511:1519 sialylated N-glycans 1500:1519 sialylated N-glycans 1500:1519 Mass spectrometry-based profiling revealed that B. infantis consumed 73% of neutral and 92% of sialylated N-glycans, while B. lactis degraded only 11% of neutral and virtually no (<1%) sialylated N-glycans. 27084007 3 56 theme glycans 680:686 arg1 range 655:659 a range 653:659 a range of intact N-linked glycans 653:686 Recently, a cell wall-associated endo-β-N-acetylglucosaminidase (EndoBI-1) found in various infant-borne bifidobacteria was shown to remove a range of intact N-linked glycans. 27084007 14 57 theme growth 2290:2295 arg1 glycoproteins 2267:2279 glycoproteins 2267:2279 glycoproteins 2267:2279 IMPORTANCE It has been previously shown that glycoproteins serve as growth substrates for bifidobacteria. 27084007 14 57 theme growth 2290:2295 arg1 substrates 2297:2306 growth substrates 2290:2306 growth substrates for bifidobacteria 2290:2325 IMPORTANCE It has been previously shown that glycoproteins serve as growth substrates for bifidobacteria. 27084007 1 58 theme nursing 305:311 arg1 infant 313:318 the nursing infant 301:318 the nursing infant 301:318 UNLABELLED Milk, in addition to nourishing the neonate, provides a range of complex glycans whose construction ensures a specific enrichment of key members of the gut microbiota in the nursing infant, a consortium known as the milk-oriented microbiome. 27084007 1 58 theme nursing 305:311 arg1 consortium 323:332 a consortium 321:332 a consortium known as the milk-oriented microbiome 321:370 UNLABELLED Milk, in addition to nourishing the neonate, provides a range of complex glycans whose construction ensures a specific enrichment of key members of the gut microbiota in the nursing infant, a consortium known as the milk-oriented microbiome. 27084007 12 59 theme milk 1905:1908 arg1 glycoproteins 1910:1922 the intact milk glycoproteins 1894:1922 the intact milk glycoproteins 1894:1922 Moreover, released N-glycans were better growth substrates than the intact milk glycoproteins, suggesting that EndoBI-1 cleavage is a key initial step in consumption of glycoproteins. 27084007 12 60 theme released 1840:1847 arg1 N-glycans 1849:1857 released N-glycans 1840:1857 released N-glycans 1840:1857 Moreover, released N-glycans were better growth substrates than the intact milk glycoproteins, suggesting that EndoBI-1 cleavage is a key initial step in consumption of glycoproteins. 27084007 2 61 theme common 476:481 arg1 bifidobacteria 461:474 bifidobacteria 461:474 bifidobacteria common to the breast-fed infant gut 461:510 Milk glycoproteins are thought to function similarly, as specific growth substrates for bifidobacteria common to the breast-fed infant gut. 27084007 9 62 theme key 1379:1381 arg1 substrate 1383:1391 the key substrate 1375:1391 the key substrate for growth 1375:1402 Conversely, B. infantis ATCC 15697 did not grow on the deglycosylated milk protein fraction, clearly demonstrating that the glycan portion of milk glycoproteins provided the key substrate for growth. 27084007 3 63 theme intact 664:669 arg1 glycans 680:686 intact N-linked glycans 664:686 intact N-linked glycans 664:686 Recently, a cell wall-associated endo-β-N-acetylglucosaminidase (EndoBI-1) found in various infant-borne bifidobacteria was shown to remove a range of intact N-linked glycans. 27084007 0 64 theme Selective 54:62 arg1 Substrates 71:80 Selective Growth Substrates 54:80 Selective Growth Substrates for Infant-Associated Bifidobacteria 54:117 Oligosaccharides Released from Milk Glycoproteins Are Selective Growth Substrates for Infant-Associated Bifidobacteria. 27084007 12 65 theme better 1864:1869 arg1 substrates 1878:1887 better growth substrates 1864:1887 better growth substrates 1864:1887 Moreover, released N-glycans were better growth substrates than the intact milk glycoproteins, suggesting that EndoBI-1 cleavage is a key initial step in consumption of glycoproteins. 27084007 18 66 theme chromatography 2826:2839 arg1 time 2857:2860 nano-liquid chromatography chip-quadrupole time 2814:2860 nano-liquid chromatography chip-quadrupole time of flight mass spectrometry [nano-LC-Chip-Q-TOF MS] 2814:2912 The selectivity of consumption of individual N-glycans was determined using advanced mass spectrometry (nano-liquid chromatography chip-quadrupole time of flight mass spectrometry [nano-LC-Chip-Q-TOF MS]) to reveal that B. infantis can consume the range of glycan structures released from whey protein concentrate. 27084007 13 67 theme bovine 2062:2067 arg1 glycoproteins 2074:2086 bovine milk glycoproteins 2062:2086 bovine milk glycoproteins 2062:2086 Finally, the variety of N-glycans released from bovine milk glycoproteins suggests that they may serve as novel prebiotic substrates with selective properties similar to those of human milk oligosaccharides. 27084007 12 68 from step 1976:1979 arg1 consumption 1984:1994 consumption 1984:1994 consumption of glycoproteins 1984:2011 Moreover, released N-glycans were better growth substrates than the intact milk glycoproteins, suggesting that EndoBI-1 cleavage is a key initial step in consumption of glycoproteins. 27084007 18 69 theme flight 2865:2870 arg1 spectrometry 2877:2888 flight mass spectrometry 2865:2888 flight mass spectrometry [nano-LC-Chip-Q-TOF MS] 2865:2912 The selectivity of consumption of individual N-glycans was determined using advanced mass spectrometry (nano-liquid chromatography chip-quadrupole time of flight mass spectrometry [nano-LC-Chip-Q-TOF MS]) to reveal that B. infantis can consume the range of glycan structures released from whey protein concentrate. 27084007 2 70 theme Milk 373:376 arg1 substrates 446:455 specific growth substrates 430:455 specific growth substrates for bifidobacteria common to the breast-fed infant gut 430:510 Milk glycoproteins are thought to function similarly, as specific growth substrates for bifidobacteria common to the breast-fed infant gut. 27084007 2 70 theme Milk 373:376 arg1 glycoproteins 378:390 Milk glycoproteins 373:390 Milk glycoproteins 373:390 Milk glycoproteins are thought to function similarly, as specific growth substrates for bifidobacteria common to the breast-fed infant gut. 27084007 10 71 dep B. 1453:1454 arg1 infantis 1456:1463 B. infantis 1453:1463 B. infantis 1453:1463 Mass spectrometry-based profiling revealed that B. infantis consumed 73% of neutral and 92% of sialylated N-glycans, while B. lactis degraded only 11% of neutral and virtually no (<1%) sialylated N-glycans. 27084007 18 72 theme protein 3004:3010 arg1 concentrate 3012:3022 whey protein concentrate 2999:3022 whey protein concentrate 2999:3022 The selectivity of consumption of individual N-glycans was determined using advanced mass spectrometry (nano-liquid chromatography chip-quadrupole time of flight mass spectrometry [nano-LC-Chip-Q-TOF MS]) to reveal that B. infantis can consume the range of glycan structures released from whey protein concentrate. 27084007 16 73 theme novel 2465:2469 arg1 enzyme 2471:2476 a novel enzyme 2463:2476 a novel enzyme 2463:2476 In this study, we used a novel enzyme to cleave conjugated N-glycans from milk glycoproteins and tested their consumption by various bifidobacteria. 27084007 18 74 theme advanced 2786:2793 arg1 spectrometry 2800:2811 advanced mass spectrometry 2786:2811 advanced mass spectrometry (nano-liquid chromatography chip-quadrupole time of flight mass spectrometry [nano-LC-Chip-Q-TOF MS]) 2786:2913 The selectivity of consumption of individual N-glycans was determined using advanced mass spectrometry (nano-liquid chromatography chip-quadrupole time of flight mass spectrometry [nano-LC-Chip-Q-TOF MS]) to reveal that B. infantis can consume the range of glycan structures released from whey protein concentrate. 27084007 18 75 theme mass 2872:2875 arg1 spectrometry 2877:2888 flight mass spectrometry 2865:2888 flight mass spectrometry [nano-LC-Chip-Q-TOF MS] 2865:2912 The selectivity of consumption of individual N-glycans was determined using advanced mass spectrometry (nano-liquid chromatography chip-quadrupole time of flight mass spectrometry [nano-LC-Chip-Q-TOF MS]) to reveal that B. infantis can consume the range of glycan structures released from whey protein concentrate. 27084007 1 76 theme key 264:266 arg1 members 268:274 key members 264:274 key members of the gut microbiota 264:296 UNLABELLED Milk, in addition to nourishing the neonate, provides a range of complex glycans whose construction ensures a specific enrichment of key members of the gut microbiota in the nursing infant, a consortium known as the milk-oriented microbiome. 27084007 14 77 gly glycoproteins 2267:2279 arg1 glycoproteins 2267:2279 glycoproteins 2267:2279 glycoproteins 2267:2279 IMPORTANCE It has been previously shown that glycoproteins serve as growth substrates for bifidobacteria. 27084007 14 77 gly glycoproteins 2267:2279 arg1 substrates 2297:2306 growth substrates 2290:2306 growth substrates for bifidobacteria 2290:2325 IMPORTANCE It has been previously shown that glycoproteins serve as growth substrates for bifidobacteria. 27084007 3 78 link N-linked 671:678 arg1 glycans 680:686 intact N-linked glycans 664:686 intact N-linked glycans 664:686 Recently, a cell wall-associated endo-β-N-acetylglucosaminidase (EndoBI-1) found in various infant-borne bifidobacteria was shown to remove a range of intact N-linked glycans. 27084007 10 79 theme no 1581:1582 arg1 N-glycans 1601:1609 neutral and virtually no (<1%) sialylated N-glycans 1559:1609 neutral and virtually no (<1%) sialylated N-glycans 1559:1609 Mass spectrometry-based profiling revealed that B. infantis consumed 73% of neutral and 92% of sialylated N-glycans, while B. lactis degraded only 11% of neutral and virtually no (<1%) sialylated N-glycans. 27084007 18 80 theme nano-liquid 2814:2824 arg1 time 2857:2860 nano-liquid chromatography chip-quadrupole time 2814:2860 nano-liquid chromatography chip-quadrupole time of flight mass spectrometry [nano-LC-Chip-Q-TOF MS] 2814:2912 The selectivity of consumption of individual N-glycans was determined using advanced mass spectrometry (nano-liquid chromatography chip-quadrupole time of flight mass spectrometry [nano-LC-Chip-Q-TOF MS]) to reveal that B. infantis can consume the range of glycan structures released from whey protein concentrate. 27084007 10 81 theme spectrometry-based 1410:1427 arg1 profiling 1429:1437 Mass spectrometry-based profiling 1405:1437 Mass spectrometry-based profiling 1405:1437 Mass spectrometry-based profiling revealed that B. infantis consumed 73% of neutral and 92% of sialylated N-glycans, while B. lactis degraded only 11% of neutral and virtually no (<1%) sialylated N-glycans. 27084007 13 82 theme human 2193:2197 arg1 oligosaccharides 2204:2219 human milk oligosaccharides 2193:2219 human milk oligosaccharides 2193:2219 Finally, the variety of N-glycans released from bovine milk glycoproteins suggests that they may serve as novel prebiotic substrates with selective properties similar to those of human milk oligosaccharides. 27084007 16 83 theme conjugated 2488:2497 arg1 N-glycans 2499:2507 conjugated N-glycans 2488:2507 conjugated N-glycans 2488:2507 In this study, we used a novel enzyme to cleave conjugated N-glycans from milk glycoproteins and tested their consumption by various bifidobacteria. 27084007 13 84 attach released 2048:2055 arg2 N-glycans 2038:2046 N-glycans 2038:2046 N-glycans released from bovine milk glycoproteins 2038:2086 Finally, the variety of N-glycans released from bovine milk glycoproteins suggests that they may serve as novel prebiotic substrates with selective properties similar to those of human milk oligosaccharides. 27084007 13 84 attach released 2048:2055 arg1 glycoproteins 2074:2086 bovine milk glycoproteins 2062:2086 bovine milk glycoproteins 2062:2086 Finally, the variety of N-glycans released from bovine milk glycoproteins suggests that they may serve as novel prebiotic substrates with selective properties similar to those of human milk oligosaccharides. 27084007 7 85 theme animalis 1143:1150 arg1 subsp 1152:1156 Bifidobacterium animalis subsp 1127:1156 Bifidobacterium animalis subsp 1127:1156 infantis (B. infantis), a species that grows well on human milk oligosaccharides, but did not support growth of Bifidobacterium animalis subsp. 27084007 9 86 theme B. 1217:1218 arg1 15697 1234:1238 B. infantis ATCC 15697 1217:1238 B. infantis ATCC 15697 1217:1238 Conversely, B. infantis ATCC 15697 did not grow on the deglycosylated milk protein fraction, clearly demonstrating that the glycan portion of milk glycoproteins provided the key substrate for growth. 27084007 3 87 theme wall-associated 530:544 arg1 EndoBI-1 578:585 EndoBI-1 578:585 EndoBI-1 578:585 Recently, a cell wall-associated endo-β-N-acetylglucosaminidase (EndoBI-1) found in various infant-borne bifidobacteria was shown to remove a range of intact N-linked glycans. 27084007 3 87 theme wall-associated 530:544 arg1 endo-β-N-acetylglucosaminidase 546:575 a cell wall-associated endo-β-N-acetylglucosaminidase 523:575 a cell wall-associated endo-β-N-acetylglucosaminidase (EndoBI-1) found in various infant-borne bifidobacteria 523:631 Recently, a cell wall-associated endo-β-N-acetylglucosaminidase (EndoBI-1) found in various infant-borne bifidobacteria was shown to remove a range of intact N-linked glycans. 27084007 11 88 gly glycoproteins 1668:1680 arg1 glycoproteins 1668:1680 N-linked glycoproteins 1659:1680 N-linked glycoproteins from milk 1659:1690 These results provide mechanistic support that N-linked glycoproteins from milk serve as selective substrates for the enrichment of infant-associated bifidobacteria capable of carrying out the initial deglycosylation. 27084007 11 88 gly glycoproteins 1668:1680 arg1 substrates 1711:1720 selective substrates 1701:1720 selective substrates for the enrichment of infant-associated bifidobacteria capable of carrying out the initial deglycosylation 1701:1827 These results provide mechanistic support that N-linked glycoproteins from milk serve as selective substrates for the enrichment of infant-associated bifidobacteria capable of carrying out the initial deglycosylation. 27084007 11 89 theme N-linked 1659:1666 arg1 glycoproteins 1668:1680 N-linked glycoproteins 1659:1680 N-linked glycoproteins from milk 1659:1690 These results provide mechanistic support that N-linked glycoproteins from milk serve as selective substrates for the enrichment of infant-associated bifidobacteria capable of carrying out the initial deglycosylation. 27084007 11 89 theme N-linked 1659:1666 arg1 substrates 1711:1720 selective substrates 1701:1720 selective substrates for the enrichment of infant-associated bifidobacteria capable of carrying out the initial deglycosylation 1701:1827 These results provide mechanistic support that N-linked glycoproteins from milk serve as selective substrates for the enrichment of infant-associated bifidobacteria capable of carrying out the initial deglycosylation. 27084007 9 90 theme ATCC 1229:1232 arg1 15697 1234:1238 B. infantis ATCC 15697 1217:1238 B. infantis ATCC 15697 1217:1238 Conversely, B. infantis ATCC 15697 did not grow on the deglycosylated milk protein fraction, clearly demonstrating that the glycan portion of milk glycoproteins provided the key substrate for growth. 27084007 8 91 dep lactis 1159:1164 arg1 lactis 1170:1175 B. lactis 1167:1175 B. lactis 1167:1175 lactis (B. lactis), a species which does not. 27084007 1 92 theme glycans 204:210 arg1 range 187:191 a range 185:191 a range of complex glycans whose construction ensures a specific enrichment of key members of the gut microbiota in the nursing infant, a consortium known as the milk-oriented microbiome 185:370 UNLABELLED Milk, in addition to nourishing the neonate, provides a range of complex glycans whose construction ensures a specific enrichment of key members of the gut microbiota in the nursing infant, a consortium known as the milk-oriented microbiome. 27084007 9 93 gly deglycosylated 1260:1273 arg1 fraction 1288:1295 the deglycosylated milk protein fraction 1256:1295 the deglycosylated milk protein fraction 1256:1295 Conversely, B. infantis ATCC 15697 did not grow on the deglycosylated milk protein fraction, clearly demonstrating that the glycan portion of milk glycoproteins provided the key substrate for growth. 27084007 12 94 theme initial 1968:1974 arg1 step 1976:1979 a key initial step 1962:1979 a key initial step in consumption of glycoproteins 1962:2011 Moreover, released N-glycans were better growth substrates than the intact milk glycoproteins, suggesting that EndoBI-1 cleavage is a key initial step in consumption of glycoproteins. 27084007 12 94 theme initial 1968:1974 arg1 cleavage 1950:1957 EndoBI-1 cleavage 1941:1957 EndoBI-1 cleavage 1941:1957 Moreover, released N-glycans were better growth substrates than the intact milk glycoproteins, suggesting that EndoBI-1 cleavage is a key initial step in consumption of glycoproteins. 27084007 17 95 theme key 2686:2688 arg1 growth 2652:2657 the growth 2648:2657 the growth 2648:2657 The results showed that the glycans selectively stimulated the growth of B. infantis, which is a key infant gut microbe. 27084007 17 95 theme key 2686:2688 arg1 microbe 2701:2707 a key infant gut microbe 2684:2707 a key infant gut microbe 2684:2707 The results showed that the glycans selectively stimulated the growth of B. infantis, which is a key infant gut microbe. 27084007 10 96 theme N-glycans 1601:1609 arg1 % 1554:1554 only 11% 1547:1554 only 11% of neutral and virtually no (<1%) sialylated N-glycans 1547:1609 Mass spectrometry-based profiling revealed that B. infantis consumed 73% of neutral and 92% of sialylated N-glycans, while B. lactis degraded only 11% of neutral and virtually no (<1%) sialylated N-glycans. 27084007 10 96 theme N-glycans 1601:1609 arg1 N-glycans 1601:1609 neutral and virtually no (<1%) sialylated N-glycans 1559:1609 neutral and virtually no (<1%) sialylated N-glycans 1559:1609 Mass spectrometry-based profiling revealed that B. infantis consumed 73% of neutral and 92% of sialylated N-glycans, while B. lactis degraded only 11% of neutral and virtually no (<1%) sialylated N-glycans. 27084007 1 97 from enrichment 250:259 arg1 infant 313:318 the nursing infant 301:318 the nursing infant 301:318 UNLABELLED Milk, in addition to nourishing the neonate, provides a range of complex glycans whose construction ensures a specific enrichment of key members of the gut microbiota in the nursing infant, a consortium known as the milk-oriented microbiome. 27084007 1 97 from enrichment 250:259 arg1 consortium 323:332 a consortium 321:332 a consortium known as the milk-oriented microbiome 321:370 UNLABELLED Milk, in addition to nourishing the neonate, provides a range of complex glycans whose construction ensures a specific enrichment of key members of the gut microbiota in the nursing infant, a consortium known as the milk-oriented microbiome. 27084007 3 98 theme infant-borne 605:616 arg1 bifidobacteria 618:631 various infant-borne bifidobacteria 597:631 various infant-borne bifidobacteria 597:631 Recently, a cell wall-associated endo-β-N-acetylglucosaminidase (EndoBI-1) found in various infant-borne bifidobacteria was shown to remove a range of intact N-linked glycans. 27084007 7 99 theme human 1068:1072 arg1 oligosaccharides 1079:1094 human milk oligosaccharides 1068:1094 human milk oligosaccharides 1068:1094 infantis (B. infantis), a species that grows well on human milk oligosaccharides, but did not support growth of Bifidobacterium animalis subsp. 27084007 6 100 theme subsp 1008:1012 arg1 growth 975:980 the rapid growth 965:980 the rapid growth of Bifidobacterium longum subsp 965:1012 EndoBI-1-released N-glycans supported the rapid growth of Bifidobacterium longum subsp. 27084007 17 101 theme gut 2697:2699 arg1 growth 2652:2657 the growth 2648:2657 the growth 2648:2657 The results showed that the glycans selectively stimulated the growth of B. infantis, which is a key infant gut microbe. 27084007 17 101 theme gut 2697:2699 arg1 microbe 2701:2707 a key infant gut microbe 2684:2707 a key infant gut microbe 2684:2707 The results showed that the glycans selectively stimulated the growth of B. infantis, which is a key infant gut microbe. 27084007 18 102 theme consumption 2729:2739 arg1 selectivity 2714:2724 The selectivity 2710:2724 The selectivity of consumption of individual N-glycans 2710:2763 The selectivity of consumption of individual N-glycans was determined using advanced mass spectrometry (nano-liquid chromatography chip-quadrupole time of flight mass spectrometry [nano-LC-Chip-Q-TOF MS]) to reveal that B. infantis can consume the range of glycan structures released from whey protein concentrate. 27084007 7 103 theme milk 1074:1077 arg1 oligosaccharides 1079:1094 human milk oligosaccharides 1068:1094 human milk oligosaccharides 1068:1094 infantis (B. infantis), a species that grows well on human milk oligosaccharides, but did not support growth of Bifidobacterium animalis subsp. 27084007 9 104 theme milk 1275:1278 arg1 fraction 1288:1295 the deglycosylated milk protein fraction 1256:1295 the deglycosylated milk protein fraction 1256:1295 Conversely, B. infantis ATCC 15697 did not grow on the deglycosylated milk protein fraction, clearly demonstrating that the glycan portion of milk glycoproteins provided the key substrate for growth. 27084007 18 105 dep spectrometry 2800:2811 arg1 time 2857:2860 nano-liquid chromatography chip-quadrupole time 2814:2860 nano-liquid chromatography chip-quadrupole time of flight mass spectrometry [nano-LC-Chip-Q-TOF MS] 2814:2912 The selectivity of consumption of individual N-glycans was determined using advanced mass spectrometry (nano-liquid chromatography chip-quadrupole time of flight mass spectrometry [nano-LC-Chip-Q-TOF MS]) to reveal that B. infantis can consume the range of glycan structures released from whey protein concentrate. 27084007 18 106 theme chip-quadrupole 2841:2855 arg1 time 2857:2860 nano-liquid chromatography chip-quadrupole time 2814:2860 nano-liquid chromatography chip-quadrupole time of flight mass spectrometry [nano-LC-Chip-Q-TOF MS] 2814:2912 The selectivity of consumption of individual N-glycans was determined using advanced mass spectrometry (nano-liquid chromatography chip-quadrupole time of flight mass spectrometry [nano-LC-Chip-Q-TOF MS]) to reveal that B. infantis can consume the range of glycan structures released from whey protein concentrate. 27084007 11 107 theme capable 1777:1783 arg1 bifidobacteria 1762:1775 infant-associated bifidobacteria 1744:1775 infant-associated bifidobacteria capable of carrying out the initial deglycosylation 1744:1827 These results provide mechanistic support that N-linked glycoproteins from milk serve as selective substrates for the enrichment of infant-associated bifidobacteria capable of carrying out the initial deglycosylation. 27084007 18 108 theme glycan 2967:2972 arg1 structures 2974:2983 glycan structures 2967:2983 glycan structures released from whey protein concentrate 2967:3022 The selectivity of consumption of individual N-glycans was determined using advanced mass spectrometry (nano-liquid chromatography chip-quadrupole time of flight mass spectrometry [nano-LC-Chip-Q-TOF MS]) to reveal that B. infantis can consume the range of glycan structures released from whey protein concentrate. 27084007 5 109 theme concentrated 877:888 arg1 colostrum 897:905 concentrated bovine colostrum 877:905 concentrated bovine colostrum 877:905 We demonstrated that EndoBI-1 released N-glycans from concentrated bovine colostrum at the pilot scale. 27084007 17 110 theme infantis 2665:2672 arg1 growth 2652:2657 the growth 2648:2657 the growth 2648:2657 The results showed that the glycans selectively stimulated the growth of B. infantis, which is a key infant gut microbe. 27084007 17 110 theme infantis 2665:2672 arg1 microbe 2701:2707 a key infant gut microbe 2684:2707 a key infant gut microbe 2684:2707 The results showed that the glycans selectively stimulated the growth of B. infantis, which is a key infant gut microbe. 27084007 11 111 theme infant-associated 1744:1760 arg1 bifidobacteria 1762:1775 infant-associated bifidobacteria 1744:1775 infant-associated bifidobacteria capable of carrying out the initial deglycosylation 1744:1827 These results provide mechanistic support that N-linked glycoproteins from milk serve as selective substrates for the enrichment of infant-associated bifidobacteria capable of carrying out the initial deglycosylation. 27084007 13 112 theme milk 2069:2072 arg1 glycoproteins 2074:2086 bovine milk glycoproteins 2062:2086 bovine milk glycoproteins 2062:2086 Finally, the variety of N-glycans released from bovine milk glycoproteins suggests that they may serve as novel prebiotic substrates with selective properties similar to those of human milk oligosaccharides. 27084007 2 113 theme breast-fed 490:499 arg1 gut 508:510 the breast-fed infant gut 486:510 the breast-fed infant gut 486:510 Milk glycoproteins are thought to function similarly, as specific growth substrates for bifidobacteria common to the breast-fed infant gut. 27084007 16 114 theme various 2565:2571 arg1 bifidobacteria 2573:2586 various bifidobacteria 2565:2586 various bifidobacteria 2565:2586 In this study, we used a novel enzyme to cleave conjugated N-glycans from milk glycoproteins and tested their consumption by various bifidobacteria. 27084007 15 115 gly glycoprotein 2353:2364 arg1 glycoprotein 2353:2364 a glycoprotein 2351:2364 a glycoprotein (glycans or polypeptides) 2351:2390 However, which part of a glycoprotein (glycans or polypeptides) is responsible for this function was not known. 27084007 4 116 theme oligosaccharide 725:739 arg1 structures 741:750 these released oligosaccharide structures 710:750 these released oligosaccharide structures 710:750 We hypothesized that these released oligosaccharide structures can serve as a sole source for the selective growth of bifidobacteria. 27084007 4 116 theme oligosaccharide 725:739 arg1 source 772:777 a sole source 765:777 a sole source for the selective growth of bifidobacteria 765:820 We hypothesized that these released oligosaccharide structures can serve as a sole source for the selective growth of bifidobacteria. 27084007 18 117 theme individual 2744:2753 arg1 N-glycans 2755:2763 individual N-glycans 2744:2763 individual N-glycans 2744:2763 The selectivity of consumption of individual N-glycans was determined using advanced mass spectrometry (nano-liquid chromatography chip-quadrupole time of flight mass spectrometry [nano-LC-Chip-Q-TOF MS]) to reveal that B. infantis can consume the range of glycan structures released from whey protein concentrate. 27084007 12 118 theme key 1964:1966 arg1 step 1976:1979 a key initial step 1962:1979 a key initial step in consumption of glycoproteins 1962:2011 Moreover, released N-glycans were better growth substrates than the intact milk glycoproteins, suggesting that EndoBI-1 cleavage is a key initial step in consumption of glycoproteins. 27084007 12 118 theme key 1964:1966 arg1 cleavage 1950:1957 EndoBI-1 cleavage 1941:1957 EndoBI-1 cleavage 1941:1957 Moreover, released N-glycans were better growth substrates than the intact milk glycoproteins, suggesting that EndoBI-1 cleavage is a key initial step in consumption of glycoproteins. 27084007 18 119 dep spectrometry 2877:2888 arg1 [nano-LC-Chip-Q-TOF 2890:2908 [nano-LC-Chip-Q-TOF 2890:2908 [nano-LC-Chip-Q-TOF 2890:2908 The selectivity of consumption of individual N-glycans was determined using advanced mass spectrometry (nano-liquid chromatography chip-quadrupole time of flight mass spectrometry [nano-LC-Chip-Q-TOF MS]) to reveal that B. infantis can consume the range of glycan structures released from whey protein concentrate. 27084007 1 120 dep nourishing 152:161 arg1 addition 140:147 addition 140:147 addition 140:147 UNLABELLED Milk, in addition to nourishing the neonate, provides a range of complex glycans whose construction ensures a specific enrichment of key members of the gut microbiota in the nursing infant, a consortium known as the milk-oriented microbiome. 27084007 10 121 gly sialylated 1590:1599 arg1 N-glycans 1601:1609 neutral and virtually no (<1%) sialylated N-glycans 1559:1609 neutral and virtually no (<1%) sialylated N-glycans 1559:1609 Mass spectrometry-based profiling revealed that B. infantis consumed 73% of neutral and 92% of sialylated N-glycans, while B. lactis degraded only 11% of neutral and virtually no (<1%) sialylated N-glycans. 27084007 4 122 theme selective 787:795 arg1 growth 797:802 the selective growth 783:802 the selective growth of bifidobacteria 783:820 We hypothesized that these released oligosaccharide structures can serve as a sole source for the selective growth of bifidobacteria. 27084007 9 123 theme glycan 1329:1334 arg1 portion 1336:1342 the glycan portion 1325:1342 the glycan portion of milk glycoproteins 1325:1364 Conversely, B. infantis ATCC 15697 did not grow on the deglycosylated milk protein fraction, clearly demonstrating that the glycan portion of milk glycoproteins provided the key substrate for growth. 27084007 12 124 theme EndoBI-1 1941:1948 arg1 step 1976:1979 a key initial step 1962:1979 a key initial step in consumption of glycoproteins 1962:2011 Moreover, released N-glycans were better growth substrates than the intact milk glycoproteins, suggesting that EndoBI-1 cleavage is a key initial step in consumption of glycoproteins. 27084007 12 124 theme EndoBI-1 1941:1948 arg1 cleavage 1950:1957 EndoBI-1 cleavage 1941:1957 EndoBI-1 cleavage 1941:1957 Moreover, released N-glycans were better growth substrates than the intact milk glycoproteins, suggesting that EndoBI-1 cleavage is a key initial step in consumption of glycoproteins. 27084007 18 125 dep [nano-LC-Chip-Q-TOF 2890:2908 arg1 MS 2910:2911 MS 2910:2911 MS 2910:2911 The selectivity of consumption of individual N-glycans was determined using advanced mass spectrometry (nano-liquid chromatography chip-quadrupole time of flight mass spectrometry [nano-LC-Chip-Q-TOF MS]) to reveal that B. infantis can consume the range of glycan structures released from whey protein concentrate. 27084007 10 126 theme neutral 1481:1487 arg1 % 1476:1476 73% 1474:1476 73% of neutral 1474:1487 Mass spectrometry-based profiling revealed that B. infantis consumed 73% of neutral and 92% of sialylated N-glycans, while B. lactis degraded only 11% of neutral and virtually no (<1%) sialylated N-glycans. 27084007 10 126 theme neutral 1481:1487 arg1 N-glycans 1511:1519 sialylated N-glycans 1500:1519 sialylated N-glycans 1500:1519 Mass spectrometry-based profiling revealed that B. infantis consumed 73% of neutral and 92% of sialylated N-glycans, while B. lactis degraded only 11% of neutral and virtually no (<1%) sialylated N-glycans. 27084007 10 126 theme neutral 1481:1487 arg1 neutral 1481:1487 neutral 1481:1487 neutral 1481:1487 Mass spectrometry-based profiling revealed that B. infantis consumed 73% of neutral and 92% of sialylated N-glycans, while B. lactis degraded only 11% of neutral and virtually no (<1%) sialylated N-glycans. 27084007 10 126 theme neutral 1481:1487 arg1 % 1495:1495 92% 1493:1495 92% of sialylated N-glycans 1493:1519 Mass spectrometry-based profiling revealed that B. infantis consumed 73% of neutral and 92% of sialylated N-glycans, while B. lactis degraded only 11% of neutral and virtually no (<1%) sialylated N-glycans. 27084007 4 127 theme sole 767:770 arg1 structures 741:750 these released oligosaccharide structures 710:750 these released oligosaccharide structures 710:750 We hypothesized that these released oligosaccharide structures can serve as a sole source for the selective growth of bifidobacteria. 27084007 4 127 theme sole 767:770 arg1 source 772:777 a sole source 765:777 a sole source for the selective growth of bifidobacteria 765:820 We hypothesized that these released oligosaccharide structures can serve as a sole source for the selective growth of bifidobacteria. 27084007 0 128 theme Milk 31:34 arg1 Glycoproteins 36:48 Milk Glycoproteins 31:48 Milk Glycoproteins 31:48 Oligosaccharides Released from Milk Glycoproteins Are Selective Growth Substrates for Infant-Associated Bifidobacteria. 27084007 9 129 theme glycoproteins 1352:1364 arg1 portion 1336:1342 the glycan portion 1325:1342 the glycan portion of milk glycoproteins 1325:1364 Conversely, B. infantis ATCC 15697 did not grow on the deglycosylated milk protein fraction, clearly demonstrating that the glycan portion of milk glycoproteins provided the key substrate for growth. 27084007 12 130 theme intact 1898:1903 arg1 glycoproteins 1910:1922 the intact milk glycoproteins 1894:1922 the intact milk glycoproteins 1894:1922 Moreover, released N-glycans were better growth substrates than the intact milk glycoproteins, suggesting that EndoBI-1 cleavage is a key initial step in consumption of glycoproteins. 27084007 2 131 theme specific 430:437 arg1 substrates 446:455 specific growth substrates 430:455 specific growth substrates for bifidobacteria common to the breast-fed infant gut 430:510 Milk glycoproteins are thought to function similarly, as specific growth substrates for bifidobacteria common to the breast-fed infant gut. 27084007 2 131 theme specific 430:437 arg1 glycoproteins 378:390 Milk glycoproteins 373:390 Milk glycoproteins 373:390 Milk glycoproteins are thought to function similarly, as specific growth substrates for bifidobacteria common to the breast-fed infant gut. 27084007 10 132 theme N-glycans 1511:1519 arg1 % 1476:1476 73% 1474:1476 73% of neutral 1474:1487 Mass spectrometry-based profiling revealed that B. infantis consumed 73% of neutral and 92% of sialylated N-glycans, while B. lactis degraded only 11% of neutral and virtually no (<1%) sialylated N-glycans. 27084007 10 132 theme N-glycans 1511:1519 arg1 N-glycans 1511:1519 sialylated N-glycans 1500:1519 sialylated N-glycans 1500:1519 Mass spectrometry-based profiling revealed that B. infantis consumed 73% of neutral and 92% of sialylated N-glycans, while B. lactis degraded only 11% of neutral and virtually no (<1%) sialylated N-glycans. 27084007 10 132 theme N-glycans 1511:1519 arg1 neutral 1481:1487 neutral 1481:1487 neutral 1481:1487 Mass spectrometry-based profiling revealed that B. infantis consumed 73% of neutral and 92% of sialylated N-glycans, while B. lactis degraded only 11% of neutral and virtually no (<1%) sialylated N-glycans. 27084007 10 132 theme N-glycans 1511:1519 arg1 % 1495:1495 92% 1493:1495 92% of sialylated N-glycans 1493:1519 Mass spectrometry-based profiling revealed that B. infantis consumed 73% of neutral and 92% of sialylated N-glycans, while B. lactis degraded only 11% of neutral and virtually no (<1%) sialylated N-glycans. 27084007 3 133 theme N-linked 671:678 arg1 glycans 680:686 intact N-linked glycans 664:686 intact N-linked glycans 664:686 Recently, a cell wall-associated endo-β-N-acetylglucosaminidase (EndoBI-1) found in various infant-borne bifidobacteria was shown to remove a range of intact N-linked glycans. 27084007 16 134 theme milk 2514:2517 arg1 glycoproteins 2519:2531 milk glycoproteins 2514:2531 milk glycoproteins 2514:2531 In this study, we used a novel enzyme to cleave conjugated N-glycans from milk glycoproteins and tested their consumption by various bifidobacteria. 27084007 13 135 theme N-glycans 2038:2046 arg1 variety 2027:2033 the variety 2023:2033 the variety of N-glycans released from bovine milk glycoproteins 2023:2086 Finally, the variety of N-glycans released from bovine milk glycoproteins suggests that they may serve as novel prebiotic substrates with selective properties similar to those of human milk oligosaccharides. 27084007 13 135 theme N-glycans 2038:2046 arg1 N-glycans 2038:2046 N-glycans 2038:2046 N-glycans released from bovine milk glycoproteins 2038:2086 Finally, the variety of N-glycans released from bovine milk glycoproteins suggests that they may serve as novel prebiotic substrates with selective properties similar to those of human milk oligosaccharides. 27084007 0 136 theme Growth 64:69 arg1 Substrates 71:80 Selective Growth Substrates 54:80 Selective Growth Substrates for Infant-Associated Bifidobacteria 54:117 Oligosaccharides Released from Milk Glycoproteins Are Selective Growth Substrates for Infant-Associated Bifidobacteria. 27084007 12 137 theme growth 1871:1876 arg1 substrates 1878:1887 better growth substrates 1864:1887 better growth substrates 1864:1887 Moreover, released N-glycans were better growth substrates than the intact milk glycoproteins, suggesting that EndoBI-1 cleavage is a key initial step in consumption of glycoproteins. 27084007 14 138 dep IMPORTANCE 2222:2231 arg1 It 2233:2234 It 2233:2234 It 2233:2234 IMPORTANCE It has been previously shown that glycoproteins serve as growth substrates for bifidobacteria. 27084007 1 139 theme specific 241:248 arg1 enrichment 250:259 a specific enrichment 239:259 a specific enrichment of key members of the gut microbiota in the nursing infant, a consortium known as the milk-oriented microbiome 239:370 UNLABELLED Milk, in addition to nourishing the neonate, provides a range of complex glycans whose construction ensures a specific enrichment of key members of the gut microbiota in the nursing infant, a consortium known as the milk-oriented microbiome. 27084007 15 140 dep glycoprotein 2353:2364 arg1 glycans 2367:2373 glycans 2367:2373 glycans 2367:2373 However, which part of a glycoprotein (glycans or polypeptides) is responsible for this function was not known. 27084007 15 140 dep glycoprotein 2353:2364 arg1 polypeptides 2378:2389 polypeptides 2378:2389 polypeptides 2378:2389 However, which part of a glycoprotein (glycans or polypeptides) is responsible for this function was not known. 27084007 11 141 theme mechanistic 1634:1644 arg1 support 1646:1652 mechanistic support that N-linked glycoproteins from milk serve as selective substrates for the enrichment of infant-associated bifidobacteria capable of carrying out the initial deglycosylation 1634:1827 mechanistic support that N-linked glycoproteins from milk serve as selective substrates for the enrichment of infant-associated bifidobacteria capable of carrying out the initial deglycosylation 1634:1827 These results provide mechanistic support that N-linked glycoproteins from milk serve as selective substrates for the enrichment of infant-associated bifidobacteria capable of carrying out the initial deglycosylation. 27084007 18 142 theme spectrometry 2877:2888 arg1 time 2857:2860 nano-liquid chromatography chip-quadrupole time 2814:2860 nano-liquid chromatography chip-quadrupole time of flight mass spectrometry [nano-LC-Chip-Q-TOF MS] 2814:2912 The selectivity of consumption of individual N-glycans was determined using advanced mass spectrometry (nano-liquid chromatography chip-quadrupole time of flight mass spectrometry [nano-LC-Chip-Q-TOF MS]) to reveal that B. infantis can consume the range of glycan structures released from whey protein concentrate. 27084007 3 143 theme cell 525:528 arg1 EndoBI-1 578:585 EndoBI-1 578:585 EndoBI-1 578:585 Recently, a cell wall-associated endo-β-N-acetylglucosaminidase (EndoBI-1) found in various infant-borne bifidobacteria was shown to remove a range of intact N-linked glycans. 27084007 3 143 theme cell 525:528 arg1 endo-β-N-acetylglucosaminidase 546:575 a cell wall-associated endo-β-N-acetylglucosaminidase 523:575 a cell wall-associated endo-β-N-acetylglucosaminidase (EndoBI-1) found in various infant-borne bifidobacteria 523:631 Recently, a cell wall-associated endo-β-N-acetylglucosaminidase (EndoBI-1) found in various infant-borne bifidobacteria was shown to remove a range of intact N-linked glycans. 27084007 18 144 theme whey 2999:3002 arg1 concentrate 3012:3022 whey protein concentrate 2999:3022 whey protein concentrate 2999:3022 The selectivity of consumption of individual N-glycans was determined using advanced mass spectrometry (nano-liquid chromatography chip-quadrupole time of flight mass spectrometry [nano-LC-Chip-Q-TOF MS]) to reveal that B. infantis can consume the range of glycan structures released from whey protein concentrate. 24936067 7 0 theme universal 1160:1168 arg1 mechanism 1170:1178 a universal mechanism 1158:1178 a universal mechanism for diverse OGTs that recognize varying acceptor proteins/peptides 1158:1245 These findings suggest that fusion with an add-on domain might be a universal mechanism for diverse OGTs that recognize varying acceptor proteins/peptides. 24936067 7 0 theme universal 1160:1168 arg1 fusion 1120:1125 fusion 1120:1125 fusion with an add-on domain 1120:1147 These findings suggest that fusion with an add-on domain might be a universal mechanism for diverse OGTs that recognize varying acceptor proteins/peptides. 24936067 1 1 theme critical 242:249 arg1 role 251:254 a critical role 240:254 a critical role 240:254 Protein glycosylation catalyzed by the O-GlcNAc transferase (OGT) plays a critical role in various biological processes. 24936067 2 2 theme repeat 467:472 arg1 protein 474:480 pneumococcal serine-rich repeat protein 442:480 pneumococcal serine-rich repeat protein 442:480 In Streptococcus pneumoniae, the core enzyme GtfA and co-activator GtfB form an OGT complex to glycosylate the serine-rich repeat (SRR) of adhesin PsrP (pneumococcal serine-rich repeat protein), which is involved in the infection and pathogenesis. 24936067 2 2 theme repeat 467:472 arg1 PsrP 436:439 adhesin PsrP 428:439 adhesin PsrP (pneumococcal serine-rich repeat protein) 428:481 In Streptococcus pneumoniae, the core enzyme GtfA and co-activator GtfB form an OGT complex to glycosylate the serine-rich repeat (SRR) of adhesin PsrP (pneumococcal serine-rich repeat protein), which is involved in the infection and pathogenesis. 24936067 6 3 dep in 976:977 arg1 vitro 979:983 vitro 979:983 vitro 979:983 In addition, the in vitro glycosylation system enables us to map the O-linkages to the serine residues within the first SRR of PsrP. 24936067 4 4 from repeats 742:748 arg1 OGTs 782:785 the only two structure-known OGTs 753:785 the only two structure-known OGTs 753:785 It represents a novel add-on domain, which is distinct from the all-α-tetratricopeptide repeats in the only two structure-known OGTs. 24936067 4 4 from repeats 742:748 arg1 distinct 700:707 distinct 700:707 distinct 700:707 It represents a novel add-on domain, which is distinct from the all-α-tetratricopeptide repeats in the only two structure-known OGTs. 24936067 4 4 from repeats 742:748 arg1 domain 683:688 a novel add-on domain 668:688 a novel add-on domain 668:688 It represents a novel add-on domain, which is distinct from the all-α-tetratricopeptide repeats in the only two structure-known OGTs. 24936067 2 5 theme co-activator 343:354 arg1 GtfB 356:359 co-activator GtfB 343:359 co-activator GtfB 343:359 In Streptococcus pneumoniae, the core enzyme GtfA and co-activator GtfB form an OGT complex to glycosylate the serine-rich repeat (SRR) of adhesin PsrP (pneumococcal serine-rich repeat protein), which is involved in the infection and pathogenesis. 24936067 2 6 dep infection 509:517 arg1 the 505:507 the 505:507 the 505:507 In Streptococcus pneumoniae, the core enzyme GtfA and co-activator GtfB form an OGT complex to glycosylate the serine-rich repeat (SRR) of adhesin PsrP (pneumococcal serine-rich repeat protein), which is involved in the infection and pathogenesis. 24936067 2 7 theme serine-rich 455:465 arg1 protein 474:480 pneumococcal serine-rich repeat protein 442:480 pneumococcal serine-rich repeat protein 442:480 In Streptococcus pneumoniae, the core enzyme GtfA and co-activator GtfB form an OGT complex to glycosylate the serine-rich repeat (SRR) of adhesin PsrP (pneumococcal serine-rich repeat protein), which is involved in the infection and pathogenesis. 24936067 2 7 theme serine-rich 455:465 arg1 PsrP 436:439 adhesin PsrP 428:439 adhesin PsrP (pneumococcal serine-rich repeat protein) 428:481 In Streptococcus pneumoniae, the core enzyme GtfA and co-activator GtfB form an OGT complex to glycosylate the serine-rich repeat (SRR) of adhesin PsrP (pneumococcal serine-rich repeat protein), which is involved in the infection and pathogenesis. 24936067 5 8 theme acceptor 941:948 arg1 protein 950:956 the acceptor protein 937:956 the acceptor protein 937:956 Structural analyses combined with binding assays indicate that this add-on domain contributes to forming an active GtfA-GtfB complex and recognizing the acceptor protein. 24936067 7 9 theme acceptor 1220:1227 arg1 proteins/peptides 1229:1245 varying acceptor proteins/peptides 1212:1245 varying acceptor proteins/peptides 1212:1245 These findings suggest that fusion with an add-on domain might be a universal mechanism for diverse OGTs that recognize varying acceptor proteins/peptides. 24936067 1 10 theme various 259:265 arg1 processes 278:286 various biological processes 259:286 various biological processes 259:286 Protein glycosylation catalyzed by the O-GlcNAc transferase (OGT) plays a critical role in various biological processes. 24936067 6 11 theme serine 1046:1051 arg1 residues 1053:1060 the serine residues 1042:1060 the serine residues within the first SRR of PsrP 1042:1089 In addition, the in vitro glycosylation system enables us to map the O-linkages to the serine residues within the first SRR of PsrP. 24936067 5 12 theme active 896:901 arg1 complex 913:919 an active GtfA-GtfB complex 893:919 an active GtfA-GtfB complex 893:919 Structural analyses combined with binding assays indicate that this add-on domain contributes to forming an active GtfA-GtfB complex and recognizing the acceptor protein. 24936067 1 13 theme Protein 168:174 arg1 glycosylation 176:188 Protein glycosylation 168:188 Protein glycosylation catalyzed by the O-GlcNAc transferase (OGT) 168:232 Protein glycosylation catalyzed by the O-GlcNAc transferase (OGT) plays a critical role in various biological processes. 24936067 2 14 gly glycosylate 384:394 arg1 SRR 420:422 SRR 420:422 SRR 420:422 In Streptococcus pneumoniae, the core enzyme GtfA and co-activator GtfB form an OGT complex to glycosylate the serine-rich repeat (SRR) of adhesin PsrP (pneumococcal serine-rich repeat protein), which is involved in the infection and pathogenesis. 24936067 2 14 gly glycosylate 384:394 arg1 repeat 412:417 the serine-rich repeat 396:417 the serine-rich repeat (SRR) 396:423 In Streptococcus pneumoniae, the core enzyme GtfA and co-activator GtfB form an OGT complex to glycosylate the serine-rich repeat (SRR) of adhesin PsrP (pneumococcal serine-rich repeat protein), which is involved in the infection and pathogenesis. 24936067 4 15 theme all-α-tetratricopeptide 718:740 arg1 repeats 742:748 the all-α-tetratricopeptide repeats 714:748 the all-α-tetratricopeptide repeats in the only two structure-known OGTs 714:785 It represents a novel add-on domain, which is distinct from the all-α-tetratricopeptide repeats in the only two structure-known OGTs. 24936067 2 16 theme adhesin 428:434 arg1 protein 474:480 pneumococcal serine-rich repeat protein 442:480 pneumococcal serine-rich repeat protein 442:480 In Streptococcus pneumoniae, the core enzyme GtfA and co-activator GtfB form an OGT complex to glycosylate the serine-rich repeat (SRR) of adhesin PsrP (pneumococcal serine-rich repeat protein), which is involved in the infection and pathogenesis. 24936067 2 16 theme adhesin 428:434 arg1 PsrP 436:439 adhesin PsrP 428:439 adhesin PsrP (pneumococcal serine-rich repeat protein) 428:481 In Streptococcus pneumoniae, the core enzyme GtfA and co-activator GtfB form an OGT complex to glycosylate the serine-rich repeat (SRR) of adhesin PsrP (pneumococcal serine-rich repeat protein), which is involved in the infection and pathogenesis. 24936067 7 17 with fusion 1120:1125 arg1 domain 1142:1147 an add-on domain 1132:1147 an add-on domain 1132:1147 These findings suggest that fusion with an add-on domain might be a universal mechanism for diverse OGTs that recognize varying acceptor proteins/peptides. 24936067 7 18 theme add-on 1135:1140 arg1 domain 1142:1147 an add-on domain 1132:1147 an add-on domain 1132:1147 These findings suggest that fusion with an add-on domain might be a universal mechanism for diverse OGTs that recognize varying acceptor proteins/peptides. 24936067 1 19 theme biological 267:276 arg1 processes 278:286 various biological processes 259:286 various biological processes 259:286 Protein glycosylation catalyzed by the O-GlcNAc transferase (OGT) plays a critical role in various biological processes. 24936067 4 20 theme add-on 676:681 arg1 distinct 700:707 distinct 700:707 distinct 700:707 It represents a novel add-on domain, which is distinct from the all-α-tetratricopeptide repeats in the only two structure-known OGTs. 24936067 4 20 theme add-on 676:681 arg1 domain 683:688 a novel add-on domain 668:688 a novel add-on domain 668:688 It represents a novel add-on domain, which is distinct from the all-α-tetratricopeptide repeats in the only two structure-known OGTs. 24936067 6 21 theme in 976:977 arg1 system 999:1004 the in vitro glycosylation system 972:1004 the in vitro glycosylation system 972:1004 In addition, the in vitro glycosylation system enables us to map the O-linkages to the serine residues within the first SRR of PsrP. 24936067 2 22 theme OGT 369:371 arg1 complex 373:379 an OGT complex 366:379 an OGT complex to glycosylate the serine-rich repeat (SRR) of adhesin PsrP (pneumococcal serine-rich repeat protein), which is involved in the infection and pathogenesis 366:534 In Streptococcus pneumoniae, the core enzyme GtfA and co-activator GtfB form an OGT complex to glycosylate the serine-rich repeat (SRR) of adhesin PsrP (pneumococcal serine-rich repeat protein), which is involved in the infection and pathogenesis. 24936067 0 23 theme novel 15:19 arg1 GtfA 77:80 GtfA 77:80 GtfA 77:80 Structure of a novel O-linked N-acetyl-D-glucosamine (O-GlcNAc) transferase, GtfA, reveals insights into the glycosylation of pneumococcal serine-rich repeat adhesins. 24936067 0 23 theme novel 15:19 arg1 transferase 64:74 a novel O-linked N-acetyl-D-glucosamine (O-GlcNAc) transferase 13:74 a novel O-linked N-acetyl-D-glucosamine (O-GlcNAc) transferase 13:74 Structure of a novel O-linked N-acetyl-D-glucosamine (O-GlcNAc) transferase, GtfA, reveals insights into the glycosylation of pneumococcal serine-rich repeat adhesins. 24936067 0 24 link O-linked 21:28 arg1 GtfA 77:80 GtfA 77:80 GtfA 77:80 Structure of a novel O-linked N-acetyl-D-glucosamine (O-GlcNAc) transferase, GtfA, reveals insights into the glycosylation of pneumococcal serine-rich repeat adhesins. 24936067 0 24 link O-linked 21:28 arg1 transferase 64:74 a novel O-linked N-acetyl-D-glucosamine (O-GlcNAc) transferase 13:74 a novel O-linked N-acetyl-D-glucosamine (O-GlcNAc) transferase 13:74 Structure of a novel O-linked N-acetyl-D-glucosamine (O-GlcNAc) transferase, GtfA, reveals insights into the glycosylation of pneumococcal serine-rich repeat adhesins. 24936067 5 25 theme Structural 788:797 arg1 analyses 799:806 Structural analyses 788:806 Structural analyses combined with binding assays 788:835 Structural analyses combined with binding assays indicate that this add-on domain contributes to forming an active GtfA-GtfB complex and recognizing the acceptor protein. 24936067 3 26 theme β-meander 601:609 arg1 domain 618:623 a β-meander add-on domain 599:623 a β-meander add-on domain 599:623 Here we report the 2.0 Å crystal structure of GtfA, revealing a β-meander add-on domain beyond the catalytic domain. 24936067 1 27 theme O-GlcNAc 207:214 arg1 OGT 229:231 OGT 229:231 OGT 229:231 Protein glycosylation catalyzed by the O-GlcNAc transferase (OGT) plays a critical role in various biological processes. 24936067 1 27 theme O-GlcNAc 207:214 arg1 transferase 216:226 O-GlcNAc transferase 207:226 the O-GlcNAc transferase (OGT) 203:232 Protein glycosylation catalyzed by the O-GlcNAc transferase (OGT) plays a critical role in various biological processes. 24936067 0 28 theme N-acetyl-D-glucosamine 30:51 arg1 GtfA 77:80 GtfA 77:80 GtfA 77:80 Structure of a novel O-linked N-acetyl-D-glucosamine (O-GlcNAc) transferase, GtfA, reveals insights into the glycosylation of pneumococcal serine-rich repeat adhesins. 24936067 0 28 theme N-acetyl-D-glucosamine 30:51 arg1 transferase 64:74 a novel O-linked N-acetyl-D-glucosamine (O-GlcNAc) transferase 13:74 a novel O-linked N-acetyl-D-glucosamine (O-GlcNAc) transferase 13:74 Structure of a novel O-linked N-acetyl-D-glucosamine (O-GlcNAc) transferase, GtfA, reveals insights into the glycosylation of pneumococcal serine-rich repeat adhesins. 24936067 6 29 theme PsrP 1086:1089 arg1 SRR 1079:1081 the first SRR 1069:1081 the first SRR of PsrP 1069:1089 In addition, the in vitro glycosylation system enables us to map the O-linkages to the serine residues within the first SRR of PsrP. 24936067 0 30 theme pneumococcal 126:137 arg1 adhesins 158:165 pneumococcal serine-rich repeat adhesins 126:165 pneumococcal serine-rich repeat adhesins 126:165 Structure of a novel O-linked N-acetyl-D-glucosamine (O-GlcNAc) transferase, GtfA, reveals insights into the glycosylation of pneumococcal serine-rich repeat adhesins. 24936067 3 31 theme add-on 611:616 arg1 domain 618:623 a β-meander add-on domain 599:623 a β-meander add-on domain 599:623 Here we report the 2.0 Å crystal structure of GtfA, revealing a β-meander add-on domain beyond the catalytic domain. 24936067 3 32 theme Å 560:560 arg1 structure 570:578 the 2.0 Å crystal structure 552:578 the 2.0 Å crystal structure of GtfA 552:586 Here we report the 2.0 Å crystal structure of GtfA, revealing a β-meander add-on domain beyond the catalytic domain. 24936067 2 33 theme serine-rich 400:410 arg1 SRR 420:422 SRR 420:422 SRR 420:422 In Streptococcus pneumoniae, the core enzyme GtfA and co-activator GtfB form an OGT complex to glycosylate the serine-rich repeat (SRR) of adhesin PsrP (pneumococcal serine-rich repeat protein), which is involved in the infection and pathogenesis. 24936067 2 33 theme serine-rich 400:410 arg1 repeat 412:417 the serine-rich repeat 396:417 the serine-rich repeat (SRR) 396:423 In Streptococcus pneumoniae, the core enzyme GtfA and co-activator GtfB form an OGT complex to glycosylate the serine-rich repeat (SRR) of adhesin PsrP (pneumococcal serine-rich repeat protein), which is involved in the infection and pathogenesis. 24936067 0 34 theme O-linked 21:28 arg1 GtfA 77:80 GtfA 77:80 GtfA 77:80 Structure of a novel O-linked N-acetyl-D-glucosamine (O-GlcNAc) transferase, GtfA, reveals insights into the glycosylation of pneumococcal serine-rich repeat adhesins. 24936067 0 34 theme O-linked 21:28 arg1 transferase 64:74 a novel O-linked N-acetyl-D-glucosamine (O-GlcNAc) transferase 13:74 a novel O-linked N-acetyl-D-glucosamine (O-GlcNAc) transferase 13:74 Structure of a novel O-linked N-acetyl-D-glucosamine (O-GlcNAc) transferase, GtfA, reveals insights into the glycosylation of pneumococcal serine-rich repeat adhesins. 24936067 2 35 theme pneumococcal 442:453 arg1 protein 474:480 pneumococcal serine-rich repeat protein 442:480 pneumococcal serine-rich repeat protein 442:480 In Streptococcus pneumoniae, the core enzyme GtfA and co-activator GtfB form an OGT complex to glycosylate the serine-rich repeat (SRR) of adhesin PsrP (pneumococcal serine-rich repeat protein), which is involved in the infection and pathogenesis. 24936067 2 35 theme pneumococcal 442:453 arg1 PsrP 436:439 adhesin PsrP 428:439 adhesin PsrP (pneumococcal serine-rich repeat protein) 428:481 In Streptococcus pneumoniae, the core enzyme GtfA and co-activator GtfB form an OGT complex to glycosylate the serine-rich repeat (SRR) of adhesin PsrP (pneumococcal serine-rich repeat protein), which is involved in the infection and pathogenesis. 24936067 3 36 theme crystal 562:568 arg1 structure 570:578 the 2.0 Å crystal structure 552:578 the 2.0 Å crystal structure of GtfA 552:586 Here we report the 2.0 Å crystal structure of GtfA, revealing a β-meander add-on domain beyond the catalytic domain. 24936067 5 37 theme binding 822:828 arg1 assays 830:835 binding assays 822:835 binding assays 822:835 Structural analyses combined with binding assays indicate that this add-on domain contributes to forming an active GtfA-GtfB complex and recognizing the acceptor protein. 24936067 0 38 theme O-GlcNAc 54:61 arg1 GtfA 77:80 GtfA 77:80 GtfA 77:80 Structure of a novel O-linked N-acetyl-D-glucosamine (O-GlcNAc) transferase, GtfA, reveals insights into the glycosylation of pneumococcal serine-rich repeat adhesins. 24936067 0 38 theme O-GlcNAc 54:61 arg1 transferase 64:74 a novel O-linked N-acetyl-D-glucosamine (O-GlcNAc) transferase 13:74 a novel O-linked N-acetyl-D-glucosamine (O-GlcNAc) transferase 13:74 Structure of a novel O-linked N-acetyl-D-glucosamine (O-GlcNAc) transferase, GtfA, reveals insights into the glycosylation of pneumococcal serine-rich repeat adhesins. 24936067 0 39 theme repeat 151:156 arg1 adhesins 158:165 pneumococcal serine-rich repeat adhesins 126:165 pneumococcal serine-rich repeat adhesins 126:165 Structure of a novel O-linked N-acetyl-D-glucosamine (O-GlcNAc) transferase, GtfA, reveals insights into the glycosylation of pneumococcal serine-rich repeat adhesins. 24936067 6 40 theme first 1073:1077 arg1 SRR 1079:1081 the first SRR 1069:1081 the first SRR of PsrP 1069:1089 In addition, the in vitro glycosylation system enables us to map the O-linkages to the serine residues within the first SRR of PsrP. 24936067 4 41 theme novel 670:674 arg1 distinct 700:707 distinct 700:707 distinct 700:707 It represents a novel add-on domain, which is distinct from the all-α-tetratricopeptide repeats in the only two structure-known OGTs. 24936067 4 41 theme novel 670:674 arg1 domain 683:688 a novel add-on domain 668:688 a novel add-on domain 668:688 It represents a novel add-on domain, which is distinct from the all-α-tetratricopeptide repeats in the only two structure-known OGTs. 24936067 2 42 theme PsrP 436:439 arg1 SRR 420:422 SRR 420:422 SRR 420:422 In Streptococcus pneumoniae, the core enzyme GtfA and co-activator GtfB form an OGT complex to glycosylate the serine-rich repeat (SRR) of adhesin PsrP (pneumococcal serine-rich repeat protein), which is involved in the infection and pathogenesis. 24936067 2 42 theme PsrP 436:439 arg1 repeat 412:417 the serine-rich repeat 396:417 the serine-rich repeat (SRR) 396:423 In Streptococcus pneumoniae, the core enzyme GtfA and co-activator GtfB form an OGT complex to glycosylate the serine-rich repeat (SRR) of adhesin PsrP (pneumococcal serine-rich repeat protein), which is involved in the infection and pathogenesis. 24936067 0 43 theme serine-rich 139:149 arg1 adhesins 158:165 pneumococcal serine-rich repeat adhesins 126:165 pneumococcal serine-rich repeat adhesins 126:165 Structure of a novel O-linked N-acetyl-D-glucosamine (O-GlcNAc) transferase, GtfA, reveals insights into the glycosylation of pneumococcal serine-rich repeat adhesins. 24936067 3 44 theme 2.0 556:558 arg1 Å 560:560 Å 560:560 Å 560:560 Here we report the 2.0 Å crystal structure of GtfA, revealing a β-meander add-on domain beyond the catalytic domain. 24936067 0 45 gly glycosylation 109:121 arg1 adhesins 158:165 pneumococcal serine-rich repeat adhesins 126:165 pneumococcal serine-rich repeat adhesins 126:165 Structure of a novel O-linked N-acetyl-D-glucosamine (O-GlcNAc) transferase, GtfA, reveals insights into the glycosylation of pneumococcal serine-rich repeat adhesins. 24936067 3 46 theme catalytic 636:644 arg1 domain 646:651 the catalytic domain 632:651 the catalytic domain 632:651 Here we report the 2.0 Å crystal structure of GtfA, revealing a β-meander add-on domain beyond the catalytic domain. 24936067 3 47 theme GtfA 583:586 arg1 structure 570:578 the 2.0 Å crystal structure 552:578 the 2.0 Å crystal structure of GtfA 552:586 Here we report the 2.0 Å crystal structure of GtfA, revealing a β-meander add-on domain beyond the catalytic domain. 24936067 4 48 theme structure-known 766:780 arg1 OGTs 782:785 the only two structure-known OGTs 753:785 the only two structure-known OGTs 753:785 It represents a novel add-on domain, which is distinct from the all-α-tetratricopeptide repeats in the only two structure-known OGTs. 24936067 2 49 theme enzyme 327:332 arg1 GtfA 334:337 the core enzyme GtfA 318:337 the core enzyme GtfA 318:337 In Streptococcus pneumoniae, the core enzyme GtfA and co-activator GtfB form an OGT complex to glycosylate the serine-rich repeat (SRR) of adhesin PsrP (pneumococcal serine-rich repeat protein), which is involved in the infection and pathogenesis. 24936067 0 50 theme adhesins 158:165 arg1 glycosylation 109:121 the glycosylation 105:121 the glycosylation of pneumococcal serine-rich repeat adhesins 105:165 Structure of a novel O-linked N-acetyl-D-glucosamine (O-GlcNAc) transferase, GtfA, reveals insights into the glycosylation of pneumococcal serine-rich repeat adhesins. 24936067 2 51 theme core 322:325 arg1 GtfA 334:337 the core enzyme GtfA 318:337 the core enzyme GtfA 318:337 In Streptococcus pneumoniae, the core enzyme GtfA and co-activator GtfB form an OGT complex to glycosylate the serine-rich repeat (SRR) of adhesin PsrP (pneumococcal serine-rich repeat protein), which is involved in the infection and pathogenesis. 24936067 5 52 theme GtfA-GtfB 903:911 arg1 complex 913:919 an active GtfA-GtfB complex 893:919 an active GtfA-GtfB complex 893:919 Structural analyses combined with binding assays indicate that this add-on domain contributes to forming an active GtfA-GtfB complex and recognizing the acceptor protein. 24936067 0 53 theme transferase 64:74 arg1 Structure 0:8 Structure 0:8 Structure of a novel O-linked N-acetyl-D-glucosamine (O-GlcNAc) transferase, GtfA, 0:81 Structure of a novel O-linked N-acetyl-D-glucosamine (O-GlcNAc) transferase, GtfA, reveals insights into the glycosylation of pneumococcal serine-rich repeat adhesins. 24936067 5 54 theme add-on 856:861 arg1 domain 863:868 this add-on domain 851:868 this add-on domain 851:868 Structural analyses combined with binding assays indicate that this add-on domain contributes to forming an active GtfA-GtfB complex and recognizing the acceptor protein. 24936067 6 55 theme glycosylation 985:997 arg1 system 999:1004 the in vitro glycosylation system 972:1004 the in vitro glycosylation system 972:1004 In addition, the in vitro glycosylation system enables us to map the O-linkages to the serine residues within the first SRR of PsrP. 24936067 7 56 theme diverse 1184:1190 arg1 OGTs 1192:1195 diverse OGTs 1184:1195 diverse OGTs that recognize varying acceptor proteins/peptides 1184:1245 These findings suggest that fusion with an add-on domain might be a universal mechanism for diverse OGTs that recognize varying acceptor proteins/peptides. 24936067 7 57 theme varying 1212:1218 arg1 proteins/peptides 1229:1245 varying acceptor proteins/peptides 1212:1245 varying acceptor proteins/peptides 1212:1245 These findings suggest that fusion with an add-on domain might be a universal mechanism for diverse OGTs that recognize varying acceptor proteins/peptides. 28582574 4 0 theme positional 460:469 arg1 cloning 471:477 the positional cloning 456:477 the positional cloning of the hmn locus 456:494 In this study, we report the positional cloning of the hmn locus and characterization of the defects caused by the mutation. 28582574 9 1 theme O-GlcNAc 1122:1129 arg1 modifications 1131:1143 these O-GlcNAc modifications 1116:1143 these O-GlcNAc modifications 1116:1143 Although some of these O-GlcNAc modifications serve an essential structural role, many others are dynamically generated on signaling molecules, including several impacting insulin signaling. 28582574 1 2 theme penetrant 117:125 arg1 mutant 162:167 a fully penetrant and expressive recessive zebrafish mutant 109:167 a fully penetrant and expressive recessive zebrafish mutant with hepatic steatosis 109:190 Recently, we identified harvest moon (hmn), a fully penetrant and expressive recessive zebrafish mutant with hepatic steatosis. 28582574 1 2 theme penetrant 117:125 arg1 moon 97:100 harvest moon 89:100 harvest moon (hmn) 89:106 Recently, we identified harvest moon (hmn), a fully penetrant and expressive recessive zebrafish mutant with hepatic steatosis. 28582574 11 3 dep mutant 1481:1486 arg1 isolated 1491:1498 isolated 1491:1498 isolated 1491:1498 Taken together with our previously reported work, the gfpt1 mutant we isolated demonstrates that global increase in O-GlcNAc modification causes some severe insulin resistance phenotypes (hepatic steatosis and runting) but does not cause hyperglycemia. 28582574 3 4 from death 395:399 arg1 period 423:428 the early juvenile period 404:428 the early juvenile period 404:428 When we attempted to raise these otherwise normal-appearing mutants to adulthood, we observed a developmental arrest and death in the early juvenile period. 28582574 12 5 theme O-GlcNAc 1735:1742 arg1 modification 1744:1755 O-GlcNAc modification 1735:1755 O-GlcNAc modification 1735:1755 This animal model will provide a platform for dissecting how O-GlcNAc modification alters insulin responsiveness in multiple tissues. 28582574 10 6 theme blood 1397:1401 arg1 glucose 1403:1409 blood glucose 1397:1409 blood glucose in males 1397:1418 We find that gfpt1 mutants show global increase in O-GlcNAc modification, and, surprisingly, lower fasting blood glucose in males. 28582574 9 7 theme insulin 1271:1277 arg1 signaling 1279:1287 insulin signaling 1271:1287 insulin signaling 1271:1287 Although some of these O-GlcNAc modifications serve an essential structural role, many others are dynamically generated on signaling molecules, including several impacting insulin signaling. 28582574 5 8 theme bulk 562:565 arg1 analysis 577:584 bulk segregant analysis 562:584 bulk segregant analysis 562:584 Using bulk segregant analysis and fine mapping, we find that hmn mutants harbor a point mutation in an invariant residue within the sugar isomerase 1 domain of the gene encoding the rate-limiting enzyme of the hexosamine biosynthetic pathway (HBP) glutamine-fructose-6-phosphate transamidase (Gfpt1). 28582574 10 9 theme global 1322:1327 arg1 increase 1329:1336 global increase 1322:1336 global increase in O-GlcNAc modification 1322:1361 We find that gfpt1 mutants show global increase in O-GlcNAc modification, and, surprisingly, lower fasting blood glucose in males. 28582574 5 10 theme hmn 617:619 arg1 mutants 621:627 hmn mutants 617:627 hmn mutants 617:627 Using bulk segregant analysis and fine mapping, we find that hmn mutants harbor a point mutation in an invariant residue within the sugar isomerase 1 domain of the gene encoding the rate-limiting enzyme of the hexosamine biosynthetic pathway (HBP) glutamine-fructose-6-phosphate transamidase (Gfpt1). 28582574 5 11 theme segregant 567:575 arg1 analysis 577:584 bulk segregant analysis 562:584 bulk segregant analysis 562:584 Using bulk segregant analysis and fine mapping, we find that hmn mutants harbor a point mutation in an invariant residue within the sugar isomerase 1 domain of the gene encoding the rate-limiting enzyme of the hexosamine biosynthetic pathway (HBP) glutamine-fructose-6-phosphate transamidase (Gfpt1). 28582574 2 12 theme defects 265:271 arg1 absence 240:246 the absence 236:246 the absence of other obvious defects 236:271 Larvae showed increased triacylglycerol in the absence of other obvious defects. 28582574 5 13 theme biosynthetic 777:788 arg1 pathway 790:796 the hexosamine biosynthetic pathway 762:796 the hexosamine biosynthetic pathway (HBP) glutamine-fructose-6-phosphate transamidase (Gfpt1) 762:854 Using bulk segregant analysis and fine mapping, we find that hmn mutants harbor a point mutation in an invariant residue within the sugar isomerase 1 domain of the gene encoding the rate-limiting enzyme of the hexosamine biosynthetic pathway (HBP) glutamine-fructose-6-phosphate transamidase (Gfpt1). 28582574 5 13 theme biosynthetic 777:788 arg1 HBP 799:801 HBP 799:801 HBP 799:801 Using bulk segregant analysis and fine mapping, we find that hmn mutants harbor a point mutation in an invariant residue within the sugar isomerase 1 domain of the gene encoding the rate-limiting enzyme of the hexosamine biosynthetic pathway (HBP) glutamine-fructose-6-phosphate transamidase (Gfpt1). 28582574 2 14 theme obvious 257:263 arg1 defects 265:271 other obvious defects 251:271 other obvious defects 251:271 Larvae showed increased triacylglycerol in the absence of other obvious defects. 28582574 5 15 theme glutamine-fructose-6-phosphate 804:833 arg1 Gfpt1 849:853 Gfpt1 849:853 Gfpt1 849:853 Using bulk segregant analysis and fine mapping, we find that hmn mutants harbor a point mutation in an invariant residue within the sugar isomerase 1 domain of the gene encoding the rate-limiting enzyme of the hexosamine biosynthetic pathway (HBP) glutamine-fructose-6-phosphate transamidase (Gfpt1). 28582574 5 15 theme glutamine-fructose-6-phosphate 804:833 arg1 transamidase 835:846 glutamine-fructose-6-phosphate transamidase 804:846 the hexosamine biosynthetic pathway (HBP) glutamine-fructose-6-phosphate transamidase (Gfpt1) 762:854 Using bulk segregant analysis and fine mapping, we find that hmn mutants harbor a point mutation in an invariant residue within the sugar isomerase 1 domain of the gene encoding the rate-limiting enzyme of the hexosamine biosynthetic pathway (HBP) glutamine-fructose-6-phosphate transamidase (Gfpt1). 28582574 1 16 theme expressive 131:140 arg1 mutant 162:167 a fully penetrant and expressive recessive zebrafish mutant 109:167 a fully penetrant and expressive recessive zebrafish mutant with hepatic steatosis 109:190 Recently, we identified harvest moon (hmn), a fully penetrant and expressive recessive zebrafish mutant with hepatic steatosis. 28582574 1 16 theme expressive 131:140 arg1 moon 97:100 harvest moon 89:100 harvest moon (hmn) 89:106 Recently, we identified harvest moon (hmn), a fully penetrant and expressive recessive zebrafish mutant with hepatic steatosis. 28582574 5 17 theme sugar 688:692 arg1 domain 706:711 the sugar isomerase 1 domain 684:711 the sugar isomerase 1 domain of the gene encoding the rate-limiting enzyme of the hexosamine biosynthetic pathway (HBP) glutamine-fructose-6-phosphate transamidase (Gfpt1) 684:854 Using bulk segregant analysis and fine mapping, we find that hmn mutants harbor a point mutation in an invariant residue within the sugar isomerase 1 domain of the gene encoding the rate-limiting enzyme of the hexosamine biosynthetic pathway (HBP) glutamine-fructose-6-phosphate transamidase (Gfpt1). 28582574 5 17 theme sugar 688:692 arg1 gene 720:723 the gene 716:723 the gene encoding the rate-limiting enzyme of the hexosamine biosynthetic pathway (HBP) glutamine-fructose-6-phosphate transamidase (Gfpt1) 716:854 Using bulk segregant analysis and fine mapping, we find that hmn mutants harbor a point mutation in an invariant residue within the sugar isomerase 1 domain of the gene encoding the rate-limiting enzyme of the hexosamine biosynthetic pathway (HBP) glutamine-fructose-6-phosphate transamidase (Gfpt1). 28582574 12 18 theme insulin 1764:1770 arg1 responsiveness 1772:1785 insulin responsiveness 1764:1785 insulin responsiveness in multiple tissues 1764:1805 This animal model will provide a platform for dissecting how O-GlcNAc modification alters insulin responsiveness in multiple tissues. 28582574 5 19 theme fine 590:593 arg1 mapping 595:601 fine mapping 590:601 fine mapping 590:601 Using bulk segregant analysis and fine mapping, we find that hmn mutants harbor a point mutation in an invariant residue within the sugar isomerase 1 domain of the gene encoding the rate-limiting enzyme of the hexosamine biosynthetic pathway (HBP) glutamine-fructose-6-phosphate transamidase (Gfpt1). 28582574 9 20 theme structural 1164:1173 arg1 role 1175:1178 an essential structural role 1151:1178 an essential structural role 1151:1178 Although some of these O-GlcNAc modifications serve an essential structural role, many others are dynamically generated on signaling molecules, including several impacting insulin signaling. 28582574 2 21 theme other 251:255 arg1 defects 265:271 other obvious defects 251:271 other obvious defects 251:271 Larvae showed increased triacylglycerol in the absence of other obvious defects. 28582574 1 22 theme recessive 142:150 arg1 mutant 162:167 a fully penetrant and expressive recessive zebrafish mutant 109:167 a fully penetrant and expressive recessive zebrafish mutant with hepatic steatosis 109:190 Recently, we identified harvest moon (hmn), a fully penetrant and expressive recessive zebrafish mutant with hepatic steatosis. 28582574 1 22 theme recessive 142:150 arg1 moon 97:100 harvest moon 89:100 harvest moon (hmn) 89:106 Recently, we identified harvest moon (hmn), a fully penetrant and expressive recessive zebrafish mutant with hepatic steatosis. 28582574 0 23 theme Genetic 2:8 arg1 Model 10:14 A Genetic Model 0:14 A Genetic Model 0:14 A Genetic Model to Study Increased Hexosamine Biosynthetic Flux. 28582574 5 24 theme isomerase 694:702 arg1 domain 706:711 the sugar isomerase 1 domain 684:711 the sugar isomerase 1 domain of the gene encoding the rate-limiting enzyme of the hexosamine biosynthetic pathway (HBP) glutamine-fructose-6-phosphate transamidase (Gfpt1) 684:854 Using bulk segregant analysis and fine mapping, we find that hmn mutants harbor a point mutation in an invariant residue within the sugar isomerase 1 domain of the gene encoding the rate-limiting enzyme of the hexosamine biosynthetic pathway (HBP) glutamine-fructose-6-phosphate transamidase (Gfpt1). 28582574 5 24 theme isomerase 694:702 arg1 gene 720:723 the gene 716:723 the gene encoding the rate-limiting enzyme of the hexosamine biosynthetic pathway (HBP) glutamine-fructose-6-phosphate transamidase (Gfpt1) 716:854 Using bulk segregant analysis and fine mapping, we find that hmn mutants harbor a point mutation in an invariant residue within the sugar isomerase 1 domain of the gene encoding the rate-limiting enzyme of the hexosamine biosynthetic pathway (HBP) glutamine-fructose-6-phosphate transamidase (Gfpt1). 28582574 8 25 theme cellular 1056:1063 arg1 proteins 1065:1072 diverse cellular proteins 1048:1072 diverse cellular proteins (O-GlcNAc modification) 1048:1096 GlcNAc can be O-linked to seryl and threonyl residues of diverse cellular proteins (O-GlcNAc modification). 28582574 8 25 theme cellular 1056:1063 arg1 modification 1084:1095 O-GlcNAc modification 1075:1095 O-GlcNAc modification 1075:1095 GlcNAc can be O-linked to seryl and threonyl residues of diverse cellular proteins (O-GlcNAc modification). 28582574 1 26 theme zebrafish 152:160 arg1 mutant 162:167 a fully penetrant and expressive recessive zebrafish mutant 109:167 a fully penetrant and expressive recessive zebrafish mutant with hepatic steatosis 109:190 Recently, we identified harvest moon (hmn), a fully penetrant and expressive recessive zebrafish mutant with hepatic steatosis. 28582574 1 26 theme zebrafish 152:160 arg1 moon 97:100 harvest moon 89:100 harvest moon (hmn) 89:106 Recently, we identified harvest moon (hmn), a fully penetrant and expressive recessive zebrafish mutant with hepatic steatosis. 28582574 3 27 theme developmental 370:382 arg1 arrest 384:389 a developmental arrest 368:389 a developmental arrest 368:389 When we attempted to raise these otherwise normal-appearing mutants to adulthood, we observed a developmental arrest and death in the early juvenile period. 28582574 10 28 from increase 1329:1336 arg1 modification 1350:1361 O-GlcNAc modification 1341:1361 O-GlcNAc modification 1341:1361 We find that gfpt1 mutants show global increase in O-GlcNAc modification, and, surprisingly, lower fasting blood glucose in males. 28582574 8 29 theme seryl 1017:1021 arg1 proteins 1065:1072 diverse cellular proteins 1048:1072 diverse cellular proteins (O-GlcNAc modification) 1048:1096 GlcNAc can be O-linked to seryl and threonyl residues of diverse cellular proteins (O-GlcNAc modification). 28582574 8 29 theme seryl 1017:1021 arg1 residues 1036:1043 seryl and threonyl residues 1017:1043 residues 1036:1043 GlcNAc can be O-linked to seryl and threonyl residues of diverse cellular proteins (O-GlcNAc modification). 28582574 11 30 theme global 1518:1523 arg1 increase 1525:1532 global increase 1518:1532 global increase in O-GlcNAc modification 1518:1557 Taken together with our previously reported work, the gfpt1 mutant we isolated demonstrates that global increase in O-GlcNAc modification causes some severe insulin resistance phenotypes (hepatic steatosis and runting) but does not cause hyperglycemia. 28582574 10 31 theme gfpt1 1303:1307 arg1 mutants 1309:1315 gfpt1 mutants 1303:1315 gfpt1 mutants 1303:1315 We find that gfpt1 mutants show global increase in O-GlcNAc modification, and, surprisingly, lower fasting blood glucose in males. 28582574 11 32 theme gfpt1 1475:1479 arg1 mutant 1481:1486 the gfpt1 mutant 1471:1486 the gfpt1 mutant we isolated 1471:1498 Taken together with our previously reported work, the gfpt1 mutant we isolated demonstrates that global increase in O-GlcNAc modification causes some severe insulin resistance phenotypes (hepatic steatosis and runting) but does not cause hyperglycemia. 28582574 3 33 theme early 408:412 arg1 period 423:428 the early juvenile period 404:428 the early juvenile period 404:428 When we attempted to raise these otherwise normal-appearing mutants to adulthood, we observed a developmental arrest and death in the early juvenile period. 28582574 11 34 theme hepatic 1609:1615 arg1 phenotypes 1597:1606 some severe insulin resistance phenotypes 1566:1606 some severe insulin resistance phenotypes (hepatic steatosis and runting) 1566:1638 Taken together with our previously reported work, the gfpt1 mutant we isolated demonstrates that global increase in O-GlcNAc modification causes some severe insulin resistance phenotypes (hepatic steatosis and runting) but does not cause hyperglycemia. 28582574 11 34 theme hepatic 1609:1615 arg1 steatosis 1617:1625 hepatic steatosis 1609:1625 hepatic steatosis 1609:1625 Taken together with our previously reported work, the gfpt1 mutant we isolated demonstrates that global increase in O-GlcNAc modification causes some severe insulin resistance phenotypes (hepatic steatosis and runting) but does not cause hyperglycemia. 28582574 9 35 theme many 1181:1184 arg1 others 1186:1191 many others 1181:1191 many others 1181:1191 Although some of these O-GlcNAc modifications serve an essential structural role, many others are dynamically generated on signaling molecules, including several impacting insulin signaling. 28582574 1 36 theme harvest 89:95 arg1 mutant 162:167 a fully penetrant and expressive recessive zebrafish mutant 109:167 a fully penetrant and expressive recessive zebrafish mutant with hepatic steatosis 109:190 Recently, we identified harvest moon (hmn), a fully penetrant and expressive recessive zebrafish mutant with hepatic steatosis. 28582574 1 36 theme harvest 89:95 arg1 hmn 103:105 hmn 103:105 hmn 103:105 Recently, we identified harvest moon (hmn), a fully penetrant and expressive recessive zebrafish mutant with hepatic steatosis. 28582574 1 36 theme harvest 89:95 arg1 moon 97:100 harvest moon 89:100 harvest moon (hmn) 89:106 Recently, we identified harvest moon (hmn), a fully penetrant and expressive recessive zebrafish mutant with hepatic steatosis. 28582574 5 37 theme hexosamine 766:775 arg1 pathway 790:796 the hexosamine biosynthetic pathway 762:796 the hexosamine biosynthetic pathway (HBP) glutamine-fructose-6-phosphate transamidase (Gfpt1) 762:854 Using bulk segregant analysis and fine mapping, we find that hmn mutants harbor a point mutation in an invariant residue within the sugar isomerase 1 domain of the gene encoding the rate-limiting enzyme of the hexosamine biosynthetic pathway (HBP) glutamine-fructose-6-phosphate transamidase (Gfpt1). 28582574 5 37 theme hexosamine 766:775 arg1 HBP 799:801 HBP 799:801 HBP 799:801 Using bulk segregant analysis and fine mapping, we find that hmn mutants harbor a point mutation in an invariant residue within the sugar isomerase 1 domain of the gene encoding the rate-limiting enzyme of the hexosamine biosynthetic pathway (HBP) glutamine-fructose-6-phosphate transamidase (Gfpt1). 28582574 11 38 theme O-GlcNAc 1537:1544 arg1 modification 1546:1557 O-GlcNAc modification 1537:1557 O-GlcNAc modification 1537:1557 Taken together with our previously reported work, the gfpt1 mutant we isolated demonstrates that global increase in O-GlcNAc modification causes some severe insulin resistance phenotypes (hepatic steatosis and runting) but does not cause hyperglycemia. 28582574 8 39 theme threonyl 1027:1034 arg1 proteins 1065:1072 diverse cellular proteins 1048:1072 diverse cellular proteins (O-GlcNAc modification) 1048:1096 GlcNAc can be O-linked to seryl and threonyl residues of diverse cellular proteins (O-GlcNAc modification). 28582574 8 39 theme threonyl 1027:1034 arg1 residues 1036:1043 seryl and threonyl residues 1017:1043 residues 1036:1043 GlcNAc can be O-linked to seryl and threonyl residues of diverse cellular proteins (O-GlcNAc modification). 28582574 11 40 dep phenotypes 1597:1606 arg1 runting 1631:1637 runting 1631:1637 runting 1631:1637 Taken together with our previously reported work, the gfpt1 mutant we isolated demonstrates that global increase in O-GlcNAc modification causes some severe insulin resistance phenotypes (hepatic steatosis and runting) but does not cause hyperglycemia. 28582574 11 40 dep phenotypes 1597:1606 arg1 phenotypes 1597:1606 some severe insulin resistance phenotypes 1566:1606 some severe insulin resistance phenotypes (hepatic steatosis and runting) 1566:1638 Taken together with our previously reported work, the gfpt1 mutant we isolated demonstrates that global increase in O-GlcNAc modification causes some severe insulin resistance phenotypes (hepatic steatosis and runting) but does not cause hyperglycemia. 28582574 11 40 dep phenotypes 1597:1606 arg1 steatosis 1617:1625 hepatic steatosis 1609:1625 hepatic steatosis 1609:1625 Taken together with our previously reported work, the gfpt1 mutant we isolated demonstrates that global increase in O-GlcNAc modification causes some severe insulin resistance phenotypes (hepatic steatosis and runting) but does not cause hyperglycemia. 28582574 1 41 theme hepatic 174:180 arg1 steatosis 182:190 hepatic steatosis 174:190 hepatic steatosis 174:190 Recently, we identified harvest moon (hmn), a fully penetrant and expressive recessive zebrafish mutant with hepatic steatosis. 28582574 0 42 theme Increased 25:33 arg1 Flux 59:62 Increased Hexosamine Biosynthetic Flux 25:62 Increased Hexosamine Biosynthetic Flux 25:62 A Genetic Model to Study Increased Hexosamine Biosynthetic Flux. 28582574 4 43 theme defects 524:530 arg1 cloning 471:477 the positional cloning 456:477 the positional cloning of the hmn locus 456:494 In this study, we report the positional cloning of the hmn locus and characterization of the defects caused by the mutation. 28582574 4 43 theme defects 524:530 arg1 characterization 500:515 characterization 500:515 characterization of the defects caused by the mutation 500:553 In this study, we report the positional cloning of the hmn locus and characterization of the defects caused by the mutation. 28582574 8 44 theme diverse 1048:1054 arg1 proteins 1065:1072 diverse cellular proteins 1048:1072 diverse cellular proteins (O-GlcNAc modification) 1048:1096 GlcNAc can be O-linked to seryl and threonyl residues of diverse cellular proteins (O-GlcNAc modification). 28582574 8 44 theme diverse 1048:1054 arg1 modification 1084:1095 O-GlcNAc modification 1075:1095 O-GlcNAc modification 1075:1095 GlcNAc can be O-linked to seryl and threonyl residues of diverse cellular proteins (O-GlcNAc modification). 28582574 12 45 from responsiveness 1772:1785 arg1 tissues 1799:1805 multiple tissues 1790:1805 multiple tissues 1790:1805 This animal model will provide a platform for dissecting how O-GlcNAc modification alters insulin responsiveness in multiple tissues. 28582574 5 46 theme invariant 659:667 arg1 residue 669:675 an invariant residue 656:675 an invariant residue within the sugar isomerase 1 domain of the gene encoding the rate-limiting enzyme of the hexosamine biosynthetic pathway (HBP) glutamine-fructose-6-phosphate transamidase (Gfpt1) 656:854 Using bulk segregant analysis and fine mapping, we find that hmn mutants harbor a point mutation in an invariant residue within the sugar isomerase 1 domain of the gene encoding the rate-limiting enzyme of the hexosamine biosynthetic pathway (HBP) glutamine-fructose-6-phosphate transamidase (Gfpt1). 28582574 5 47 theme pathway 790:796 arg1 enzyme 752:757 the rate-limiting enzyme 734:757 the rate-limiting enzyme of the hexosamine biosynthetic pathway (HBP) glutamine-fructose-6-phosphate transamidase (Gfpt1) 734:854 Using bulk segregant analysis and fine mapping, we find that hmn mutants harbor a point mutation in an invariant residue within the sugar isomerase 1 domain of the gene encoding the rate-limiting enzyme of the hexosamine biosynthetic pathway (HBP) glutamine-fructose-6-phosphate transamidase (Gfpt1). 28582574 3 48 theme juvenile 414:421 arg1 period 423:428 the early juvenile period 404:428 the early juvenile period 404:428 When we attempted to raise these otherwise normal-appearing mutants to adulthood, we observed a developmental arrest and death in the early juvenile period. 28582574 4 49 theme locus 490:494 arg1 cloning 471:477 the positional cloning 456:477 the positional cloning of the hmn locus 456:494 In this study, we report the positional cloning of the hmn locus and characterization of the defects caused by the mutation. 28582574 4 49 theme locus 490:494 arg1 characterization 500:515 characterization 500:515 characterization of the defects caused by the mutation 500:553 In this study, we report the positional cloning of the hmn locus and characterization of the defects caused by the mutation. 28582574 5 50 theme gene 720:723 arg1 domain 706:711 the sugar isomerase 1 domain 684:711 the sugar isomerase 1 domain of the gene encoding the rate-limiting enzyme of the hexosamine biosynthetic pathway (HBP) glutamine-fructose-6-phosphate transamidase (Gfpt1) 684:854 Using bulk segregant analysis and fine mapping, we find that hmn mutants harbor a point mutation in an invariant residue within the sugar isomerase 1 domain of the gene encoding the rate-limiting enzyme of the hexosamine biosynthetic pathway (HBP) glutamine-fructose-6-phosphate transamidase (Gfpt1). 28582574 5 50 theme gene 720:723 arg1 gene 720:723 the gene 716:723 the gene encoding the rate-limiting enzyme of the hexosamine biosynthetic pathway (HBP) glutamine-fructose-6-phosphate transamidase (Gfpt1) 716:854 Using bulk segregant analysis and fine mapping, we find that hmn mutants harbor a point mutation in an invariant residue within the sugar isomerase 1 domain of the gene encoding the rate-limiting enzyme of the hexosamine biosynthetic pathway (HBP) glutamine-fructose-6-phosphate transamidase (Gfpt1). 28582574 2 51 theme increased 207:215 arg1 triacylglycerol 217:231 increased triacylglycerol 207:231 increased triacylglycerol 207:231 Larvae showed increased triacylglycerol in the absence of other obvious defects. 28582574 7 52 from glucose 982:988 arg1 pathway 969:975 a spillover pathway 957:975 a spillover pathway from glucose 957:988 The HBP generates β-N-acetyl-glucosamine (GlcNAc) as a spillover pathway from glucose. 28582574 7 52 from glucose 982:988 arg1 β-N-acetyl-glucosamine 922:943 β-N-acetyl-glucosamine 922:943 β-N-acetyl-glucosamine (GlcNAc) 922:952 The HBP generates β-N-acetyl-glucosamine (GlcNAc) as a spillover pathway from glucose. 28582574 0 53 theme Biosynthetic 46:57 arg1 Flux 59:62 Increased Hexosamine Biosynthetic Flux 25:62 Increased Hexosamine Biosynthetic Flux 25:62 A Genetic Model to Study Increased Hexosamine Biosynthetic Flux. 28582574 4 54 theme hmn 486:488 arg1 locus 490:494 the hmn locus 482:494 the hmn locus 482:494 In this study, we report the positional cloning of the hmn locus and characterization of the defects caused by the mutation. 28582574 8 55 theme proteins 1065:1072 arg1 proteins 1065:1072 diverse cellular proteins 1048:1072 diverse cellular proteins (O-GlcNAc modification) 1048:1096 GlcNAc can be O-linked to seryl and threonyl residues of diverse cellular proteins (O-GlcNAc modification). 28582574 8 55 theme proteins 1065:1072 arg1 residues 1036:1043 seryl and threonyl residues 1017:1043 residues 1036:1043 GlcNAc can be O-linked to seryl and threonyl residues of diverse cellular proteins (O-GlcNAc modification). 28582574 11 56 theme severe 1571:1576 arg1 runting 1631:1637 runting 1631:1637 runting 1631:1637 Taken together with our previously reported work, the gfpt1 mutant we isolated demonstrates that global increase in O-GlcNAc modification causes some severe insulin resistance phenotypes (hepatic steatosis and runting) but does not cause hyperglycemia. 28582574 11 56 theme severe 1571:1576 arg1 phenotypes 1597:1606 some severe insulin resistance phenotypes 1566:1606 some severe insulin resistance phenotypes (hepatic steatosis and runting) 1566:1638 Taken together with our previously reported work, the gfpt1 mutant we isolated demonstrates that global increase in O-GlcNAc modification causes some severe insulin resistance phenotypes (hepatic steatosis and runting) but does not cause hyperglycemia. 28582574 11 56 theme severe 1571:1576 arg1 steatosis 1617:1625 hepatic steatosis 1609:1625 hepatic steatosis 1609:1625 Taken together with our previously reported work, the gfpt1 mutant we isolated demonstrates that global increase in O-GlcNAc modification causes some severe insulin resistance phenotypes (hepatic steatosis and runting) but does not cause hyperglycemia. 28582574 10 57 from glucose 1403:1409 arg1 males 1414:1418 males 1414:1418 males 1414:1418 We find that gfpt1 mutants show global increase in O-GlcNAc modification, and, surprisingly, lower fasting blood glucose in males. 28582574 0 58 theme Hexosamine 35:44 arg1 Flux 59:62 Increased Hexosamine Biosynthetic Flux 25:62 Increased Hexosamine Biosynthetic Flux 25:62 A Genetic Model to Study Increased Hexosamine Biosynthetic Flux. 28582574 1 59 with mutant 162:167 arg1 steatosis 182:190 hepatic steatosis 174:190 hepatic steatosis 174:190 Recently, we identified harvest moon (hmn), a fully penetrant and expressive recessive zebrafish mutant with hepatic steatosis. 28582574 6 60 theme mutated 861:867 arg1 protein 869:875 The mutated protein 857:875 The mutated protein 857:875 The mutated protein shows increased abundance. 28582574 7 61 theme spillover 959:967 arg1 pathway 969:975 a spillover pathway 957:975 a spillover pathway from glucose 957:988 The HBP generates β-N-acetyl-glucosamine (GlcNAc) as a spillover pathway from glucose. 28582574 7 61 theme spillover 959:967 arg1 β-N-acetyl-glucosamine 922:943 β-N-acetyl-glucosamine 922:943 β-N-acetyl-glucosamine (GlcNAc) 922:952 The HBP generates β-N-acetyl-glucosamine (GlcNAc) as a spillover pathway from glucose. 28582574 11 62 from increase 1525:1532 arg1 modification 1546:1557 O-GlcNAc modification 1537:1557 O-GlcNAc modification 1537:1557 Taken together with our previously reported work, the gfpt1 mutant we isolated demonstrates that global increase in O-GlcNAc modification causes some severe insulin resistance phenotypes (hepatic steatosis and runting) but does not cause hyperglycemia. 28582574 11 63 theme reported 1456:1463 arg1 work 1465:1468 our previously reported work 1441:1468 our previously reported work 1441:1468 Taken together with our previously reported work, the gfpt1 mutant we isolated demonstrates that global increase in O-GlcNAc modification causes some severe insulin resistance phenotypes (hepatic steatosis and runting) but does not cause hyperglycemia. 28582574 6 64 theme increased 883:891 arg1 abundance 893:901 increased abundance 883:901 increased abundance 883:901 The mutated protein shows increased abundance. 28582574 8 65 theme O-GlcNAc 1075:1082 arg1 proteins 1065:1072 diverse cellular proteins 1048:1072 diverse cellular proteins (O-GlcNAc modification) 1048:1096 GlcNAc can be O-linked to seryl and threonyl residues of diverse cellular proteins (O-GlcNAc modification). 28582574 8 65 theme O-GlcNAc 1075:1082 arg1 modification 1084:1095 O-GlcNAc modification 1075:1095 O-GlcNAc modification 1075:1095 GlcNAc can be O-linked to seryl and threonyl residues of diverse cellular proteins (O-GlcNAc modification). 28582574 9 66 theme signaling 1222:1230 arg1 molecules 1232:1240 signaling molecules 1222:1240 signaling molecules 1222:1240 Although some of these O-GlcNAc modifications serve an essential structural role, many others are dynamically generated on signaling molecules, including several impacting insulin signaling. 28582574 9 66 theme signaling 1222:1230 arg1 several 1253:1259 several 1253:1259 several 1253:1259 Although some of these O-GlcNAc modifications serve an essential structural role, many others are dynamically generated on signaling molecules, including several impacting insulin signaling. 28582574 5 67 dep pathway 790:796 arg1 Gfpt1 849:853 Gfpt1 849:853 Gfpt1 849:853 Using bulk segregant analysis and fine mapping, we find that hmn mutants harbor a point mutation in an invariant residue within the sugar isomerase 1 domain of the gene encoding the rate-limiting enzyme of the hexosamine biosynthetic pathway (HBP) glutamine-fructose-6-phosphate transamidase (Gfpt1). 28582574 5 67 dep pathway 790:796 arg1 transamidase 835:846 glutamine-fructose-6-phosphate transamidase 804:846 the hexosamine biosynthetic pathway (HBP) glutamine-fructose-6-phosphate transamidase (Gfpt1) 762:854 Using bulk segregant analysis and fine mapping, we find that hmn mutants harbor a point mutation in an invariant residue within the sugar isomerase 1 domain of the gene encoding the rate-limiting enzyme of the hexosamine biosynthetic pathway (HBP) glutamine-fructose-6-phosphate transamidase (Gfpt1). 28582574 12 68 theme multiple 1790:1797 arg1 tissues 1799:1805 multiple tissues 1790:1805 multiple tissues 1790:1805 This animal model will provide a platform for dissecting how O-GlcNAc modification alters insulin responsiveness in multiple tissues. 28582574 5 69 theme point 638:642 arg1 mutation 644:651 a point mutation 636:651 a point mutation 636:651 Using bulk segregant analysis and fine mapping, we find that hmn mutants harbor a point mutation in an invariant residue within the sugar isomerase 1 domain of the gene encoding the rate-limiting enzyme of the hexosamine biosynthetic pathway (HBP) glutamine-fructose-6-phosphate transamidase (Gfpt1). 28582574 10 70 theme O-GlcNAc 1341:1348 arg1 modification 1350:1361 O-GlcNAc modification 1341:1361 O-GlcNAc modification 1341:1361 We find that gfpt1 mutants show global increase in O-GlcNAc modification, and, surprisingly, lower fasting blood glucose in males. 28582574 9 71 theme essential 1154:1162 arg1 role 1175:1178 an essential structural role 1151:1178 an essential structural role 1151:1178 Although some of these O-GlcNAc modifications serve an essential structural role, many others are dynamically generated on signaling molecules, including several impacting insulin signaling. 28582574 3 72 theme otherwise 307:315 arg1 mutants 334:340 these otherwise normal-appearing mutants 301:340 these otherwise normal-appearing mutants 301:340 When we attempted to raise these otherwise normal-appearing mutants to adulthood, we observed a developmental arrest and death in the early juvenile period. 28582574 8 73 attach O-linked 1005:1012 arg1 proteins 1065:1072 diverse cellular proteins 1048:1072 diverse cellular proteins (O-GlcNAc modification) 1048:1096 GlcNAc can be O-linked to seryl and threonyl residues of diverse cellular proteins (O-GlcNAc modification). 28582574 8 73 attach O-linked 1005:1012 arg1 residues 1036:1043 seryl and threonyl residues 1017:1043 residues 1036:1043 GlcNAc can be O-linked to seryl and threonyl residues of diverse cellular proteins (O-GlcNAc modification). 28582574 8 73 attach O-linked 1005:1012 arg2 GlcNAc 991:996 GlcNAc 991:996 GlcNAc 991:996 GlcNAc can be O-linked to seryl and threonyl residues of diverse cellular proteins (O-GlcNAc modification). 28582574 12 74 theme animal 1679:1684 arg1 model 1686:1690 This animal model 1674:1690 This animal model 1674:1690 This animal model will provide a platform for dissecting how O-GlcNAc modification alters insulin responsiveness in multiple tissues. 28582574 3 75 theme normal-appearing 317:332 arg1 mutants 334:340 these otherwise normal-appearing mutants 301:340 these otherwise normal-appearing mutants 301:340 When we attempted to raise these otherwise normal-appearing mutants to adulthood, we observed a developmental arrest and death in the early juvenile period. 28582574 3 76 from arrest 384:389 arg1 period 423:428 the early juvenile period 404:428 the early juvenile period 404:428 When we attempted to raise these otherwise normal-appearing mutants to adulthood, we observed a developmental arrest and death in the early juvenile period. 28582574 11 77 theme insulin 1578:1584 arg1 runting 1631:1637 runting 1631:1637 runting 1631:1637 Taken together with our previously reported work, the gfpt1 mutant we isolated demonstrates that global increase in O-GlcNAc modification causes some severe insulin resistance phenotypes (hepatic steatosis and runting) but does not cause hyperglycemia. 28582574 11 77 theme insulin 1578:1584 arg1 phenotypes 1597:1606 some severe insulin resistance phenotypes 1566:1606 some severe insulin resistance phenotypes (hepatic steatosis and runting) 1566:1638 Taken together with our previously reported work, the gfpt1 mutant we isolated demonstrates that global increase in O-GlcNAc modification causes some severe insulin resistance phenotypes (hepatic steatosis and runting) but does not cause hyperglycemia. 28582574 11 77 theme insulin 1578:1584 arg1 steatosis 1617:1625 hepatic steatosis 1609:1625 hepatic steatosis 1609:1625 Taken together with our previously reported work, the gfpt1 mutant we isolated demonstrates that global increase in O-GlcNAc modification causes some severe insulin resistance phenotypes (hepatic steatosis and runting) but does not cause hyperglycemia. 28582574 5 78 theme rate-limiting 738:750 arg1 enzyme 752:757 the rate-limiting enzyme 734:757 the rate-limiting enzyme of the hexosamine biosynthetic pathway (HBP) glutamine-fructose-6-phosphate transamidase (Gfpt1) 734:854 Using bulk segregant analysis and fine mapping, we find that hmn mutants harbor a point mutation in an invariant residue within the sugar isomerase 1 domain of the gene encoding the rate-limiting enzyme of the hexosamine biosynthetic pathway (HBP) glutamine-fructose-6-phosphate transamidase (Gfpt1). 28582574 11 79 theme resistance 1586:1595 arg1 runting 1631:1637 runting 1631:1637 runting 1631:1637 Taken together with our previously reported work, the gfpt1 mutant we isolated demonstrates that global increase in O-GlcNAc modification causes some severe insulin resistance phenotypes (hepatic steatosis and runting) but does not cause hyperglycemia. 28582574 11 79 theme resistance 1586:1595 arg1 phenotypes 1597:1606 some severe insulin resistance phenotypes 1566:1606 some severe insulin resistance phenotypes (hepatic steatosis and runting) 1566:1638 Taken together with our previously reported work, the gfpt1 mutant we isolated demonstrates that global increase in O-GlcNAc modification causes some severe insulin resistance phenotypes (hepatic steatosis and runting) but does not cause hyperglycemia. 28582574 11 79 theme resistance 1586:1595 arg1 steatosis 1617:1625 hepatic steatosis 1609:1625 hepatic steatosis 1609:1625 Taken together with our previously reported work, the gfpt1 mutant we isolated demonstrates that global increase in O-GlcNAc modification causes some severe insulin resistance phenotypes (hepatic steatosis and runting) but does not cause hyperglycemia. 28024295 4 0 theme direct 468:473 arg1 sequencing 475:484 direct sequencing 468:484 direct sequencing 468:484 The molecular analysis using direct sequencing revealed two novel mutations in FANCG; 2 novel mutations c.1143+5G>C and c.883dupG, and a reported mutation c.1471_1473delAAAinsG. 28024295 4 1 dep mutations 533:541 arg1 mutations 533:541 2 novel mutations 525:541 2 novel mutations c.1143+5G>C and c.883dupG 525:567 The molecular analysis using direct sequencing revealed two novel mutations in FANCG; 2 novel mutations c.1143+5G>C and c.883dupG, and a reported mutation c.1471_1473delAAAinsG. 28024295 4 1 dep mutations 533:541 arg1 c.883dupG 559:567 c.883dupG 559:567 c.883dupG 559:567 The molecular analysis using direct sequencing revealed two novel mutations in FANCG; 2 novel mutations c.1143+5G>C and c.883dupG, and a reported mutation c.1471_1473delAAAinsG. 28024295 4 1 dep mutations 533:541 arg1 c.1143+5G>C 543:553 c.1143+5G>C 543:553 c.1143+5G>C 543:553 The molecular analysis using direct sequencing revealed two novel mutations in FANCG; 2 novel mutations c.1143+5G>C and c.883dupG, and a reported mutation c.1471_1473delAAAinsG. 28024295 5 2 theme FANCG 652:656 arg1 protein 658:664 FANCG protein 652:664 FANCG protein with fold based template search 652:696 We have for the first time modeled FANCG protein with fold based template search using pGenthreader which revealed sequence fold identical to super helical TPR domain of O linked GLCNAC transferase and have studied the impact of mutations on the function and structure of FANCG. 28024295 1 3 theme X-linked 139:146 arg1 mode 148:151 autosomal or X-linked mode 126:151 mode 148:151 FA is a rare recessive genetic disorder with autosomal or X-linked mode of inheritance and is associated with 19 different FA complementation groups. 28024295 5 4 theme super 759:763 arg1 transferase 803:813 O linked GLCNAC transferase 787:813 O linked GLCNAC transferase 787:813 We have for the first time modeled FANCG protein with fold based template search using pGenthreader which revealed sequence fold identical to super helical TPR domain of O linked GLCNAC transferase and have studied the impact of mutations on the function and structure of FANCG. 28024295 5 4 theme super 759:763 arg1 domain 777:782 super helical TPR domain 759:782 super helical TPR domain of O linked GLCNAC transferase 759:813 We have for the first time modeled FANCG protein with fold based template search using pGenthreader which revealed sequence fold identical to super helical TPR domain of O linked GLCNAC transferase and have studied the impact of mutations on the function and structure of FANCG. 28024295 4 5 theme reported 576:583 arg1 c.1471_1473delAAAinsG 594:614 a reported mutation c.1471_1473delAAAinsG 574:614 a reported mutation c.1471_1473delAAAinsG 574:614 The molecular analysis using direct sequencing revealed two novel mutations in FANCG; 2 novel mutations c.1143+5G>C and c.883dupG, and a reported mutation c.1471_1473delAAAinsG. 28024295 3 6 from non-monoubiquitination 395:416 arg1 cultures 375:382 MMC induced blood cultures 357:382 MMC induced blood cultures 357:382 All three patients showed a high frequency chromosomal breakage in MMC induced blood cultures and FANCD2 non-monoubiquitination by western blotting. 28024295 5 7 with protein 658:664 arg1 search 691:696 fold based template search 671:696 fold based template search 671:696 We have for the first time modeled FANCG protein with fold based template search using pGenthreader which revealed sequence fold identical to super helical TPR domain of O linked GLCNAC transferase and have studied the impact of mutations on the function and structure of FANCG. 28024295 6 8 theme FA 1008:1009 arg1 pathway 1011:1017 FA pathway 1008:1017 FA pathway 1008:1017 All three mutations are potential pathogenic molecular changes which can affect FANCG interactions required for FA pathway, homologous recombination repairs and unhooking step of the ICL repair process. 28024295 4 9 from c.1471_1473delAAAinsG 594:614 arg1 FANCG 518:522 FANCG 518:522 FANCG 518:522 The molecular analysis using direct sequencing revealed two novel mutations in FANCG; 2 novel mutations c.1143+5G>C and c.883dupG, and a reported mutation c.1471_1473delAAAinsG. 28024295 0 10 from Characterization 0:15 arg1 patients 71:78 Indian Fanconi anemia patients 49:78 Indian Fanconi anemia patients 49:78 Characterization of two novel FANCG mutations in Indian Fanconi anemia patients. 28024295 6 11 theme unhooking 1057:1065 arg1 step 1067:1070 unhooking step 1057:1070 unhooking step of the ICL repair process 1057:1096 All three mutations are potential pathogenic molecular changes which can affect FANCG interactions required for FA pathway, homologous recombination repairs and unhooking step of the ICL repair process. 28024295 5 12 theme identical 746:754 arg1 fold 741:744 sequence fold 732:744 sequence fold identical to super helical TPR domain of O linked GLCNAC transferase 732:813 We have for the first time modeled FANCG protein with fold based template search using pGenthreader which revealed sequence fold identical to super helical TPR domain of O linked GLCNAC transferase and have studied the impact of mutations on the function and structure of FANCG. 28024295 4 13 from mutations 505:513 arg1 FANCG 518:522 FANCG 518:522 FANCG 518:522 The molecular analysis using direct sequencing revealed two novel mutations in FANCG; 2 novel mutations c.1143+5G>C and c.883dupG, and a reported mutation c.1471_1473delAAAinsG. 28024295 4 14 theme mutation 585:592 arg1 c.1471_1473delAAAinsG 594:614 a reported mutation c.1471_1473delAAAinsG 574:614 a reported mutation c.1471_1473delAAAinsG 574:614 The molecular analysis using direct sequencing revealed two novel mutations in FANCG; 2 novel mutations c.1143+5G>C and c.883dupG, and a reported mutation c.1471_1473delAAAinsG. 28024295 3 15 theme frequency 323:331 arg1 breakage 345:352 a high frequency chromosomal breakage 316:352 a high frequency chromosomal breakage in MMC induced blood cultures 316:382 All three patients showed a high frequency chromosomal breakage in MMC induced blood cultures and FANCD2 non-monoubiquitination by western blotting. 28024295 1 16 with disorder 112:119 arg1 mode 148:151 autosomal or X-linked mode 126:151 mode 148:151 FA is a rare recessive genetic disorder with autosomal or X-linked mode of inheritance and is associated with 19 different FA complementation groups. 28024295 6 17 theme process 1090:1096 arg1 step 1067:1070 unhooking step 1057:1070 unhooking step of the ICL repair process 1057:1096 All three mutations are potential pathogenic molecular changes which can affect FANCG interactions required for FA pathway, homologous recombination repairs and unhooking step of the ICL repair process. 28024295 6 17 theme process 1090:1096 arg1 pathway 1011:1017 FA pathway 1008:1017 FA pathway 1008:1017 All three mutations are potential pathogenic molecular changes which can affect FANCG interactions required for FA pathway, homologous recombination repairs and unhooking step of the ICL repair process. 28024295 6 17 theme process 1090:1096 arg1 recombination 1031:1043 homologous recombination repairs 1020:1051 homologous recombination repairs 1020:1051 All three mutations are potential pathogenic molecular changes which can affect FANCG interactions required for FA pathway, homologous recombination repairs and unhooking step of the ICL repair process. 28024295 6 18 theme ICL 1079:1081 arg1 process 1090:1096 the ICL repair process 1075:1096 the ICL repair process 1075:1096 All three mutations are potential pathogenic molecular changes which can affect FANCG interactions required for FA pathway, homologous recombination repairs and unhooking step of the ICL repair process. 28024295 5 19 theme linked 789:794 arg1 transferase 803:813 O linked GLCNAC transferase 787:813 O linked GLCNAC transferase 787:813 We have for the first time modeled FANCG protein with fold based template search using pGenthreader which revealed sequence fold identical to super helical TPR domain of O linked GLCNAC transferase and have studied the impact of mutations on the function and structure of FANCG. 28024295 3 20 theme chromosomal 333:343 arg1 breakage 345:352 a high frequency chromosomal breakage 316:352 a high frequency chromosomal breakage in MMC induced blood cultures 316:382 All three patients showed a high frequency chromosomal breakage in MMC induced blood cultures and FANCD2 non-monoubiquitination by western blotting. 28024295 0 21 from mutations 36:44 arg1 patients 71:78 Indian Fanconi anemia patients 49:78 Indian Fanconi anemia patients 49:78 Characterization of two novel FANCG mutations in Indian Fanconi anemia patients. 28024295 5 22 theme first 633:637 arg1 time 639:642 the first time 629:642 the first time 629:642 We have for the first time modeled FANCG protein with fold based template search using pGenthreader which revealed sequence fold identical to super helical TPR domain of O linked GLCNAC transferase and have studied the impact of mutations on the function and structure of FANCG. 28024295 1 23 theme inheritance 156:166 arg1 mode 148:151 autosomal or X-linked mode 126:151 mode 148:151 FA is a rare recessive genetic disorder with autosomal or X-linked mode of inheritance and is associated with 19 different FA complementation groups. 28024295 3 24 theme blood 369:373 arg1 cultures 375:382 MMC induced blood cultures 357:382 MMC induced blood cultures 357:382 All three patients showed a high frequency chromosomal breakage in MMC induced blood cultures and FANCD2 non-monoubiquitination by western blotting. 28024295 6 25 dep recombination 1031:1043 arg1 repairs 1045:1051 repairs 1045:1051 repairs 1045:1051 All three mutations are potential pathogenic molecular changes which can affect FANCG interactions required for FA pathway, homologous recombination repairs and unhooking step of the ICL repair process. 28024295 5 26 theme helical 765:771 arg1 transferase 803:813 O linked GLCNAC transferase 787:813 O linked GLCNAC transferase 787:813 We have for the first time modeled FANCG protein with fold based template search using pGenthreader which revealed sequence fold identical to super helical TPR domain of O linked GLCNAC transferase and have studied the impact of mutations on the function and structure of FANCG. 28024295 5 26 theme helical 765:771 arg1 domain 777:782 super helical TPR domain 759:782 super helical TPR domain of O linked GLCNAC transferase 759:813 We have for the first time modeled FANCG protein with fold based template search using pGenthreader which revealed sequence fold identical to super helical TPR domain of O linked GLCNAC transferase and have studied the impact of mutations on the function and structure of FANCG. 28024295 3 27 theme western 421:427 arg1 blotting 429:436 western blotting 421:436 western blotting 421:436 All three patients showed a high frequency chromosomal breakage in MMC induced blood cultures and FANCD2 non-monoubiquitination by western blotting. 28024295 5 28 dep linked 789:794 arg1 O 787:787 O 787:787 O 787:787 We have for the first time modeled FANCG protein with fold based template search using pGenthreader which revealed sequence fold identical to super helical TPR domain of O linked GLCNAC transferase and have studied the impact of mutations on the function and structure of FANCG. 28024295 4 29 theme molecular 443:451 arg1 analysis 453:460 The molecular analysis 439:460 The molecular analysis using direct sequencing 439:484 The molecular analysis using direct sequencing revealed two novel mutations in FANCG; 2 novel mutations c.1143+5G>C and c.883dupG, and a reported mutation c.1471_1473delAAAinsG. 28024295 0 30 theme novel 24:28 arg1 mutations 36:44 two novel FANCG mutations 20:44 two novel FANCG mutations in Indian Fanconi anemia patients 20:78 Characterization of two novel FANCG mutations in Indian Fanconi anemia patients. 28024295 6 31 theme FANCG 976:980 arg1 interactions 982:993 FANCG interactions 976:993 FANCG interactions required for FA pathway, homologous recombination repairs and unhooking step of the ICL repair process 976:1096 All three mutations are potential pathogenic molecular changes which can affect FANCG interactions required for FA pathway, homologous recombination repairs and unhooking step of the ICL repair process. 28024295 1 32 link X-linked 139:146 arg1 mode 148:151 autosomal or X-linked mode 126:151 mode 148:151 FA is a rare recessive genetic disorder with autosomal or X-linked mode of inheritance and is associated with 19 different FA complementation groups. 28024295 5 33 dep function 863:870 arg1 the 859:861 the 859:861 the 859:861 We have for the first time modeled FANCG protein with fold based template search using pGenthreader which revealed sequence fold identical to super helical TPR domain of O linked GLCNAC transferase and have studied the impact of mutations on the function and structure of FANCG. 28024295 5 34 theme GLCNAC 796:801 arg1 transferase 803:813 O linked GLCNAC transferase 787:813 O linked GLCNAC transferase 787:813 We have for the first time modeled FANCG protein with fold based template search using pGenthreader which revealed sequence fold identical to super helical TPR domain of O linked GLCNAC transferase and have studied the impact of mutations on the function and structure of FANCG. 28024295 3 35 theme induced 361:367 arg1 cultures 375:382 MMC induced blood cultures 357:382 MMC induced blood cultures 357:382 All three patients showed a high frequency chromosomal breakage in MMC induced blood cultures and FANCD2 non-monoubiquitination by western blotting. 28024295 1 36 theme rare 89:92 arg1 disorder 112:119 a rare recessive genetic disorder 87:119 a rare recessive genetic disorder with autosomal or X-linked mode of inheritance 87:166 FA is a rare recessive genetic disorder with autosomal or X-linked mode of inheritance and is associated with 19 different FA complementation groups. 28024295 1 36 theme rare 89:92 arg1 FA 81:82 FA 81:82 FA 81:82 FA is a rare recessive genetic disorder with autosomal or X-linked mode of inheritance and is associated with 19 different FA complementation groups. 28024295 0 37 theme mutations 36:44 arg1 Characterization 0:15 Characterization 0:15 Characterization of two novel FANCG mutations in Indian Fanconi anemia patients. 0:79 Characterization of two novel FANCG mutations in Indian Fanconi anemia patients. 28024295 0 38 from patients 71:78 arg1 Characterization 0:15 Characterization 0:15 Characterization of two novel FANCG mutations in Indian Fanconi anemia patients. 0:79 Characterization of two novel FANCG mutations in Indian Fanconi anemia patients. 28024295 5 39 theme sequence 732:739 arg1 fold 741:744 sequence fold 732:744 sequence fold identical to super helical TPR domain of O linked GLCNAC transferase 732:813 We have for the first time modeled FANCG protein with fold based template search using pGenthreader which revealed sequence fold identical to super helical TPR domain of O linked GLCNAC transferase and have studied the impact of mutations on the function and structure of FANCG. 28024295 5 40 theme mutations 846:854 arg1 impact 836:841 the impact 832:841 the impact of mutations on the function and structure of FANCG 832:893 We have for the first time modeled FANCG protein with fold based template search using pGenthreader which revealed sequence fold identical to super helical TPR domain of O linked GLCNAC transferase and have studied the impact of mutations on the function and structure of FANCG. 28024295 0 41 theme FANCG 30:34 arg1 mutations 36:44 two novel FANCG mutations 20:44 two novel FANCG mutations in Indian Fanconi anemia patients 20:78 Characterization of two novel FANCG mutations in Indian Fanconi anemia patients. 28024295 4 42 theme novel 527:531 arg1 mutations 533:541 2 novel mutations 525:541 2 novel mutations c.1143+5G>C and c.883dupG 525:567 The molecular analysis using direct sequencing revealed two novel mutations in FANCG; 2 novel mutations c.1143+5G>C and c.883dupG, and a reported mutation c.1471_1473delAAAinsG. 28024295 4 42 theme novel 527:531 arg1 c.883dupG 559:567 c.883dupG 559:567 c.883dupG 559:567 The molecular analysis using direct sequencing revealed two novel mutations in FANCG; 2 novel mutations c.1143+5G>C and c.883dupG, and a reported mutation c.1471_1473delAAAinsG. 28024295 4 42 theme novel 527:531 arg1 c.1143+5G>C 543:553 c.1143+5G>C 543:553 c.1143+5G>C 543:553 The molecular analysis using direct sequencing revealed two novel mutations in FANCG; 2 novel mutations c.1143+5G>C and c.883dupG, and a reported mutation c.1471_1473delAAAinsG. 28024295 4 43 from mutations 533:541 arg1 FANCG 518:522 FANCG 518:522 FANCG 518:522 The molecular analysis using direct sequencing revealed two novel mutations in FANCG; 2 novel mutations c.1143+5G>C and c.883dupG, and a reported mutation c.1471_1473delAAAinsG. 28024295 3 44 from breakage 345:352 arg1 cultures 375:382 MMC induced blood cultures 357:382 MMC induced blood cultures 357:382 All three patients showed a high frequency chromosomal breakage in MMC induced blood cultures and FANCD2 non-monoubiquitination by western blotting. 28024295 3 45 theme MMC 357:359 arg1 cultures 375:382 MMC induced blood cultures 357:382 MMC induced blood cultures 357:382 All three patients showed a high frequency chromosomal breakage in MMC induced blood cultures and FANCD2 non-monoubiquitination by western blotting. 28024295 1 46 theme different 194:202 arg1 groups 223:228 19 different FA complementation groups 191:228 19 different FA complementation groups 191:228 FA is a rare recessive genetic disorder with autosomal or X-linked mode of inheritance and is associated with 19 different FA complementation groups. 28024295 0 47 theme Indian 49:54 arg1 anemia 64:69 Indian Fanconi anemia 49:69 Indian Fanconi anemia patients 49:78 Characterization of two novel FANCG mutations in Indian Fanconi anemia patients. 28024295 5 48 theme transferase 803:813 arg1 transferase 803:813 O linked GLCNAC transferase 787:813 O linked GLCNAC transferase 787:813 We have for the first time modeled FANCG protein with fold based template search using pGenthreader which revealed sequence fold identical to super helical TPR domain of O linked GLCNAC transferase and have studied the impact of mutations on the function and structure of FANCG. 28024295 5 48 theme transferase 803:813 arg1 domain 777:782 super helical TPR domain 759:782 super helical TPR domain of O linked GLCNAC transferase 759:813 We have for the first time modeled FANCG protein with fold based template search using pGenthreader which revealed sequence fold identical to super helical TPR domain of O linked GLCNAC transferase and have studied the impact of mutations on the function and structure of FANCG. 28024295 3 49 theme high 318:321 arg1 breakage 345:352 a high frequency chromosomal breakage 316:352 a high frequency chromosomal breakage in MMC induced blood cultures 316:382 All three patients showed a high frequency chromosomal breakage in MMC induced blood cultures and FANCD2 non-monoubiquitination by western blotting. 28024295 4 50 theme novel 499:503 arg1 mutations 505:513 two novel mutations 495:513 two novel mutations in FANCG 495:522 The molecular analysis using direct sequencing revealed two novel mutations in FANCG; 2 novel mutations c.1143+5G>C and c.883dupG, and a reported mutation c.1471_1473delAAAinsG. 28024295 1 51 theme recessive 94:102 arg1 disorder 112:119 a rare recessive genetic disorder 87:119 a rare recessive genetic disorder with autosomal or X-linked mode of inheritance 87:166 FA is a rare recessive genetic disorder with autosomal or X-linked mode of inheritance and is associated with 19 different FA complementation groups. 28024295 1 51 theme recessive 94:102 arg1 FA 81:82 FA 81:82 FA 81:82 FA is a rare recessive genetic disorder with autosomal or X-linked mode of inheritance and is associated with 19 different FA complementation groups. 28024295 3 52 theme FANCD2 388:393 arg1 non-monoubiquitination 395:416 FANCD2 non-monoubiquitination 388:416 FANCD2 non-monoubiquitination 388:416 All three patients showed a high frequency chromosomal breakage in MMC induced blood cultures and FANCD2 non-monoubiquitination by western blotting. 28024295 6 53 theme molecular 941:949 arg1 changes 951:957 potential pathogenic molecular changes 920:957 potential pathogenic molecular changes which can affect FANCG interactions required for FA pathway, homologous recombination repairs and unhooking step of the ICL repair process 920:1096 All three mutations are potential pathogenic molecular changes which can affect FANCG interactions required for FA pathway, homologous recombination repairs and unhooking step of the ICL repair process. 28024295 6 53 theme molecular 941:949 arg1 mutations 906:914 All three mutations 896:914 All three mutations 896:914 All three mutations are potential pathogenic molecular changes which can affect FANCG interactions required for FA pathway, homologous recombination repairs and unhooking step of the ICL repair process. 28024295 5 54 theme template 682:689 arg1 search 691:696 fold based template search 671:696 fold based template search 671:696 We have for the first time modeled FANCG protein with fold based template search using pGenthreader which revealed sequence fold identical to super helical TPR domain of O linked GLCNAC transferase and have studied the impact of mutations on the function and structure of FANCG. 28024295 5 55 link linked 789:794 arg1 transferase 803:813 O linked GLCNAC transferase 787:813 O linked GLCNAC transferase 787:813 We have for the first time modeled FANCG protein with fold based template search using pGenthreader which revealed sequence fold identical to super helical TPR domain of O linked GLCNAC transferase and have studied the impact of mutations on the function and structure of FANCG. 28024295 5 56 from impact 836:841 arg1 function 863:870 function 863:870 function 863:870 We have for the first time modeled FANCG protein with fold based template search using pGenthreader which revealed sequence fold identical to super helical TPR domain of O linked GLCNAC transferase and have studied the impact of mutations on the function and structure of FANCG. 28024295 5 56 from impact 836:841 arg1 structure 876:884 structure 876:884 structure 876:884 We have for the first time modeled FANCG protein with fold based template search using pGenthreader which revealed sequence fold identical to super helical TPR domain of O linked GLCNAC transferase and have studied the impact of mutations on the function and structure of FANCG. 28024295 1 57 theme genetic 104:110 arg1 disorder 112:119 a rare recessive genetic disorder 87:119 a rare recessive genetic disorder with autosomal or X-linked mode of inheritance 87:166 FA is a rare recessive genetic disorder with autosomal or X-linked mode of inheritance and is associated with 19 different FA complementation groups. 28024295 1 57 theme genetic 104:110 arg1 FA 81:82 FA 81:82 FA 81:82 FA is a rare recessive genetic disorder with autosomal or X-linked mode of inheritance and is associated with 19 different FA complementation groups. 28024295 6 58 theme pathogenic 930:939 arg1 changes 951:957 potential pathogenic molecular changes 920:957 potential pathogenic molecular changes which can affect FANCG interactions required for FA pathway, homologous recombination repairs and unhooking step of the ICL repair process 920:1096 All three mutations are potential pathogenic molecular changes which can affect FANCG interactions required for FA pathway, homologous recombination repairs and unhooking step of the ICL repair process. 28024295 6 58 theme pathogenic 930:939 arg1 mutations 906:914 All three mutations 896:914 All three mutations 896:914 All three mutations are potential pathogenic molecular changes which can affect FANCG interactions required for FA pathway, homologous recombination repairs and unhooking step of the ICL repair process. 28024295 5 59 theme based 676:680 arg1 search 691:696 fold based template search 671:696 fold based template search 671:696 We have for the first time modeled FANCG protein with fold based template search using pGenthreader which revealed sequence fold identical to super helical TPR domain of O linked GLCNAC transferase and have studied the impact of mutations on the function and structure of FANCG. 28024295 5 60 theme TPR 773:775 arg1 transferase 803:813 O linked GLCNAC transferase 787:813 O linked GLCNAC transferase 787:813 We have for the first time modeled FANCG protein with fold based template search using pGenthreader which revealed sequence fold identical to super helical TPR domain of O linked GLCNAC transferase and have studied the impact of mutations on the function and structure of FANCG. 28024295 5 60 theme TPR 773:775 arg1 domain 777:782 super helical TPR domain 759:782 super helical TPR domain of O linked GLCNAC transferase 759:813 We have for the first time modeled FANCG protein with fold based template search using pGenthreader which revealed sequence fold identical to super helical TPR domain of O linked GLCNAC transferase and have studied the impact of mutations on the function and structure of FANCG. 28024295 1 61 theme FA 204:205 arg1 groups 223:228 19 different FA complementation groups 191:228 19 different FA complementation groups 191:228 FA is a rare recessive genetic disorder with autosomal or X-linked mode of inheritance and is associated with 19 different FA complementation groups. 28024295 1 62 theme complementation 207:221 arg1 groups 223:228 19 different FA complementation groups 191:228 19 different FA complementation groups 191:228 FA is a rare recessive genetic disorder with autosomal or X-linked mode of inheritance and is associated with 19 different FA complementation groups. 28024295 0 63 theme anemia 64:69 arg1 patients 71:78 Indian Fanconi anemia patients 49:78 Indian Fanconi anemia patients 49:78 Characterization of two novel FANCG mutations in Indian Fanconi anemia patients. 28024295 1 64 theme autosomal 126:134 arg1 mode 148:151 autosomal or X-linked mode 126:151 mode 148:151 FA is a rare recessive genetic disorder with autosomal or X-linked mode of inheritance and is associated with 19 different FA complementation groups. 28024295 6 65 theme repair 1083:1088 arg1 process 1090:1096 the ICL repair process 1075:1096 the ICL repair process 1075:1096 All three mutations are potential pathogenic molecular changes which can affect FANCG interactions required for FA pathway, homologous recombination repairs and unhooking step of the ICL repair process. 28024295 6 66 theme homologous 1020:1029 arg1 recombination 1031:1043 homologous recombination repairs 1020:1051 homologous recombination repairs 1020:1051 All three mutations are potential pathogenic molecular changes which can affect FANCG interactions required for FA pathway, homologous recombination repairs and unhooking step of the ICL repair process. 28024295 0 67 theme Fanconi 56:62 arg1 anemia 64:69 Indian Fanconi anemia 49:69 Indian Fanconi anemia patients 49:78 Characterization of two novel FANCG mutations in Indian Fanconi anemia patients. 28024295 6 68 theme potential 920:928 arg1 changes 951:957 potential pathogenic molecular changes 920:957 potential pathogenic molecular changes which can affect FANCG interactions required for FA pathway, homologous recombination repairs and unhooking step of the ICL repair process 920:1096 All three mutations are potential pathogenic molecular changes which can affect FANCG interactions required for FA pathway, homologous recombination repairs and unhooking step of the ICL repair process. 28024295 6 68 theme potential 920:928 arg1 mutations 906:914 All three mutations 896:914 All three mutations 896:914 All three mutations are potential pathogenic molecular changes which can affect FANCG interactions required for FA pathway, homologous recombination repairs and unhooking step of the ICL repair process. 28024295 5 69 theme FANCG 889:893 arg1 function 863:870 function 863:870 function 863:870 We have for the first time modeled FANCG protein with fold based template search using pGenthreader which revealed sequence fold identical to super helical TPR domain of O linked GLCNAC transferase and have studied the impact of mutations on the function and structure of FANCG. 28024295 5 69 theme FANCG 889:893 arg1 structure 876:884 structure 876:884 structure 876:884 We have for the first time modeled FANCG protein with fold based template search using pGenthreader which revealed sequence fold identical to super helical TPR domain of O linked GLCNAC transferase and have studied the impact of mutations on the function and structure of FANCG. 28013366 6 0 theme major 1316:1320 arg1 impact 1322:1327 a major impact 1314:1327 a major impact of tissue fixation 1314:1346 Flanking cytofluorimetric assays on lectin binding to native cells gave similar grading, excluding a major impact of tissue fixation. 28013366 2 1 theme lectin 365:370 arg1 binding 372:378 lectin binding 365:378 lectin binding 365:378 As a consequence, assays to assess inhibition of lectin binding should necessarily come as close as possible to the physiological situation, to characterize an impact of a synthetic compound on biorelevant binding with pharmaceutical perspective. 28013366 6 2 theme Flanking 1215:1222 arg1 assays 1241:1246 Flanking cytofluorimetric assays 1215:1246 Flanking cytofluorimetric assays on lectin binding to native cells 1215:1280 Flanking cytofluorimetric assays on lectin binding to native cells gave similar grading, excluding a major impact of tissue fixation. 28013366 1 3 theme glycoproteins 285:297 arg1 abundance 263:271 the natural abundance 251:271 the natural abundance of cellular glycoproteins and glycolipids 251:313 A hallmark of endogenous lectins is their ability to select a few distinct glycoconjugates as counterreceptors for functional pairing from the natural abundance of cellular glycoproteins and glycolipids. 28013366 7 4 theme inhibitor 1491:1499 arg1 effect 1478:1483 the effect 1474:1483 the effect of an inhibitor in a certain context 1474:1520 The experiments revealed cell/tissue binding of galectin-8 preferentially via one domain, depending on the cell type so that the effect of an inhibitor in a certain context cannot be extrapolated to other cells/tissues. 28013366 1 5 theme few 174:176 arg1 glycoconjugates 187:201 a few distinct glycoconjugates 172:201 a few distinct glycoconjugates as counterreceptors for functional pairing from the natural abundance of cellular glycoproteins and glycolipids 172:313 A hallmark of endogenous lectins is their ability to select a few distinct glycoconjugates as counterreceptors for functional pairing from the natural abundance of cellular glycoproteins and glycolipids. 28013366 7 6 from effect 1478:1483 arg1 context 1514:1520 a certain context 1504:1520 a certain context 1504:1520 The experiments revealed cell/tissue binding of galectin-8 preferentially via one domain, depending on the cell type so that the effect of an inhibitor in a certain context cannot be extrapolated to other cells/tissues. 28013366 8 7 theme inhibitory 1768:1777 arg1 profiles 1779:1786 inhibitory profiles 1768:1786 inhibitory profiles 1768:1786 Moreover, the work with the other galectins attests that this assay enables comprehensive analysis of the galectin network in serial tissue sections to determine overlaps and regional differences in inhibitory profiles. 28013366 3 8 dep tissue 652:657 arg1 epididymis 669:678 epididymis 669:678 epididymis 669:678 We here introduce in a proof-of-principle manner work with sections of paraffin-embedded tissue (jejunum, epididymis) and labeled adhesion/growth-regulatory galectins, harboring one (galectin-1 and galectin-3) or two (galectin-8) types of lectin domain. 28013366 3 8 dep tissue 652:657 arg1 jejunum 660:666 jejunum 660:666 jejunum 660:666 We here introduce in a proof-of-principle manner work with sections of paraffin-embedded tissue (jejunum, epididymis) and labeled adhesion/growth-regulatory galectins, harboring one (galectin-1 and galectin-3) or two (galectin-8) types of lectin domain. 28013366 4 9 theme O-linked 946:953 arg1 extensions 955:964 O-linked extensions 946:964 O-linked extensions 946:964 Six pairs of synthetic lactosides from tailoring of the headgroup (3'-O-sulfation) and the aglycone (β-methyl to aromatic S- and O-linked extensions) as well as three bi- to tetravalent glycoclusters were used as test compounds. 28013366 3 10 theme lectin 802:807 arg1 domain 809:814 lectin domain 802:814 lectin domain 802:814 We here introduce in a proof-of-principle manner work with sections of paraffin-embedded tissue (jejunum, epididymis) and labeled adhesion/growth-regulatory galectins, harboring one (galectin-1 and galectin-3) or two (galectin-8) types of lectin domain. 28013366 8 11 with work 1583:1586 arg1 galectins 1603:1611 the other galectins 1593:1611 the other galectins 1593:1611 Moreover, the work with the other galectins attests that this assay enables comprehensive analysis of the galectin network in serial tissue sections to determine overlaps and regional differences in inhibitory profiles. 28013366 4 12 from tailoring 856:864 arg1 pairs 821:825 Six pairs 817:825 Six pairs of synthetic lactosides from tailoring of the headgroup (3'-O-sulfation) and the aglycone (β-methyl to aromatic S- and O-linked extensions) as well as three bi- to tetravalent glycoclusters 817:1015 Six pairs of synthetic lactosides from tailoring of the headgroup (3'-O-sulfation) and the aglycone (β-methyl to aromatic S- and O-linked extensions) as well as three bi- to tetravalent glycoclusters were used as test compounds. 28013366 4 12 from tailoring 856:864 arg1 lactosides 840:849 synthetic lactosides 830:849 synthetic lactosides from tailoring of the headgroup (3'-O-sulfation) and the aglycone (β-methyl to aromatic S- and O-linked extensions) as well as three bi- to tetravalent glycoclusters 830:1015 Six pairs of synthetic lactosides from tailoring of the headgroup (3'-O-sulfation) and the aglycone (β-methyl to aromatic S- and O-linked extensions) as well as three bi- to tetravalent glycoclusters were used as test compounds. 28013366 4 12 from tailoring 856:864 arg1 compounds 1035:1043 test compounds 1030:1043 test compounds 1030:1043 Six pairs of synthetic lactosides from tailoring of the headgroup (3'-O-sulfation) and the aglycone (β-methyl to aromatic S- and O-linked extensions) as well as three bi- to tetravalent glycoclusters were used as test compounds. 28013366 1 13 theme functional 227:236 arg1 pairing 238:244 functional pairing 227:244 functional pairing from the natural abundance of cellular glycoproteins and glycolipids 227:313 A hallmark of endogenous lectins is their ability to select a few distinct glycoconjugates as counterreceptors for functional pairing from the natural abundance of cellular glycoproteins and glycolipids. 28013366 3 14 dep one 741:743 arg1 galectin-3 761:770 galectin-3 761:770 galectin-3 761:770 We here introduce in a proof-of-principle manner work with sections of paraffin-embedded tissue (jejunum, epididymis) and labeled adhesion/growth-regulatory galectins, harboring one (galectin-1 and galectin-3) or two (galectin-8) types of lectin domain. 28013366 3 14 dep one 741:743 arg1 galectin-1 746:755 galectin-1 746:755 galectin-1 746:755 We here introduce in a proof-of-principle manner work with sections of paraffin-embedded tissue (jejunum, epididymis) and labeled adhesion/growth-regulatory galectins, harboring one (galectin-1 and galectin-3) or two (galectin-8) types of lectin domain. 28013366 3 14 dep one 741:743 arg1 types 793:797 types 793:797 types of lectin domain 793:814 We here introduce in a proof-of-principle manner work with sections of paraffin-embedded tissue (jejunum, epididymis) and labeled adhesion/growth-regulatory galectins, harboring one (galectin-1 and galectin-3) or two (galectin-8) types of lectin domain. 28013366 8 15 from analysis 1659:1666 arg1 sections 1709:1716 serial tissue sections 1695:1716 serial tissue sections 1695:1716 Moreover, the work with the other galectins attests that this assay enables comprehensive analysis of the galectin network in serial tissue sections to determine overlaps and regional differences in inhibitory profiles. 28013366 6 16 theme fixation 1339:1346 arg1 impact 1322:1327 a major impact 1314:1327 a major impact of tissue fixation 1314:1346 Flanking cytofluorimetric assays on lectin binding to native cells gave similar grading, excluding a major impact of tissue fixation. 28013366 5 17 theme Varying 1046:1052 arg1 extents 1054:1060 Varying extents 1046:1060 Varying extents of reduction in staining intensity by synthetic compounds relative to unsubstituted/free lactose 1046:1157 Varying extents of reduction in staining intensity by synthetic compounds relative to unsubstituted/free lactose proved the applicability and sensitivity of the method. 28013366 1 18 theme endogenous 126:135 arg1 lectins 137:143 endogenous lectins 126:143 endogenous lectins 126:143 A hallmark of endogenous lectins is their ability to select a few distinct glycoconjugates as counterreceptors for functional pairing from the natural abundance of cellular glycoproteins and glycolipids. 28013366 6 19 theme lectin 1251:1256 arg1 binding 1258:1264 lectin binding 1251:1264 lectin binding to native cells 1251:1280 Flanking cytofluorimetric assays on lectin binding to native cells gave similar grading, excluding a major impact of tissue fixation. 28013366 7 20 theme galectin-8 1397:1406 arg1 binding 1386:1392 cell/tissue binding 1374:1392 cell/tissue binding of galectin-8 1374:1406 The experiments revealed cell/tissue binding of galectin-8 preferentially via one domain, depending on the cell type so that the effect of an inhibitor in a certain context cannot be extrapolated to other cells/tissues. 28013366 2 21 dep assays 334:339 arg1 assess 344:349 assess 344:349 to assess inhibition of lectin binding 341:378 As a consequence, assays to assess inhibition of lectin binding should necessarily come as close as possible to the physiological situation, to characterize an impact of a synthetic compound on biorelevant binding with pharmaceutical perspective. 28013366 2 22 theme biorelevant 510:520 arg1 binding 522:528 biorelevant binding 510:528 biorelevant binding with pharmaceutical perspective 510:560 As a consequence, assays to assess inhibition of lectin binding should necessarily come as close as possible to the physiological situation, to characterize an impact of a synthetic compound on biorelevant binding with pharmaceutical perspective. 28013366 5 23 from reduction 1065:1073 arg1 intensity 1087:1095 staining intensity 1078:1095 staining intensity 1078:1095 Varying extents of reduction in staining intensity by synthetic compounds relative to unsubstituted/free lactose proved the applicability and sensitivity of the method. 28013366 5 24 theme unsubstituted/free 1132:1149 arg1 lactose 1151:1157 unsubstituted/free lactose 1132:1157 unsubstituted/free lactose 1132:1157 Varying extents of reduction in staining intensity by synthetic compounds relative to unsubstituted/free lactose proved the applicability and sensitivity of the method. 28013366 3 25 theme tissue 652:657 arg1 sections 622:629 sections 622:629 sections 622:629 We here introduce in a proof-of-principle manner work with sections of paraffin-embedded tissue (jejunum, epididymis) and labeled adhesion/growth-regulatory galectins, harboring one (galectin-1 and galectin-3) or two (galectin-8) types of lectin domain. 28013366 2 26 theme compound 498:505 arg1 impact 476:481 an impact 473:481 an impact of a synthetic compound on biorelevant binding with pharmaceutical perspective 473:560 As a consequence, assays to assess inhibition of lectin binding should necessarily come as close as possible to the physiological situation, to characterize an impact of a synthetic compound on biorelevant binding with pharmaceutical perspective. 28013366 4 27 dep aglycone 908:915 arg1 β-methyl 918:925 β-methyl 918:925 β-methyl 918:925 Six pairs of synthetic lactosides from tailoring of the headgroup (3'-O-sulfation) and the aglycone (β-methyl to aromatic S- and O-linked extensions) as well as three bi- to tetravalent glycoclusters were used as test compounds. 28013366 5 28 theme synthetic 1100:1108 arg1 compounds 1110:1118 synthetic compounds 1100:1118 synthetic compounds relative to unsubstituted/free lactose 1100:1157 Varying extents of reduction in staining intensity by synthetic compounds relative to unsubstituted/free lactose proved the applicability and sensitivity of the method. 28013366 8 29 from network 1684:1690 arg1 sections 1709:1716 serial tissue sections 1695:1716 serial tissue sections 1695:1716 Moreover, the work with the other galectins attests that this assay enables comprehensive analysis of the galectin network in serial tissue sections to determine overlaps and regional differences in inhibitory profiles. 28013366 5 30 theme relative 1120:1127 arg1 compounds 1110:1118 synthetic compounds 1100:1118 synthetic compounds relative to unsubstituted/free lactose 1100:1157 Varying extents of reduction in staining intensity by synthetic compounds relative to unsubstituted/free lactose proved the applicability and sensitivity of the method. 28013366 7 31 theme cell/tissue 1374:1384 arg1 binding 1386:1392 cell/tissue binding 1374:1392 cell/tissue binding of galectin-8 1374:1406 The experiments revealed cell/tissue binding of galectin-8 preferentially via one domain, depending on the cell type so that the effect of an inhibitor in a certain context cannot be extrapolated to other cells/tissues. 28013366 4 32 theme test 1030:1033 arg1 pairs 821:825 Six pairs 817:825 Six pairs of synthetic lactosides from tailoring of the headgroup (3'-O-sulfation) and the aglycone (β-methyl to aromatic S- and O-linked extensions) as well as three bi- to tetravalent glycoclusters 817:1015 Six pairs of synthetic lactosides from tailoring of the headgroup (3'-O-sulfation) and the aglycone (β-methyl to aromatic S- and O-linked extensions) as well as three bi- to tetravalent glycoclusters were used as test compounds. 28013366 4 32 theme test 1030:1033 arg1 compounds 1035:1043 test compounds 1030:1043 test compounds 1030:1043 Six pairs of synthetic lactosides from tailoring of the headgroup (3'-O-sulfation) and the aglycone (β-methyl to aromatic S- and O-linked extensions) as well as three bi- to tetravalent glycoclusters were used as test compounds. 28013366 1 33 gly glycoproteins 285:297 arg1 glycoproteins 285:297 cellular glycoproteins 276:297 cellular glycoproteins 276:297 A hallmark of endogenous lectins is their ability to select a few distinct glycoconjugates as counterreceptors for functional pairing from the natural abundance of cellular glycoproteins and glycolipids. 28013366 8 34 from sections 1709:1716 arg1 analysis 1659:1666 comprehensive analysis 1645:1666 comprehensive analysis of the galectin network in serial tissue sections 1645:1716 Moreover, the work with the other galectins attests that this assay enables comprehensive analysis of the galectin network in serial tissue sections to determine overlaps and regional differences in inhibitory profiles. 28013366 8 35 from differences 1753:1763 arg1 profiles 1779:1786 inhibitory profiles 1768:1786 inhibitory profiles 1768:1786 Moreover, the work with the other galectins attests that this assay enables comprehensive analysis of the galectin network in serial tissue sections to determine overlaps and regional differences in inhibitory profiles. 28013366 2 36 theme physiological 432:444 arg1 situation 446:454 the physiological situation 428:454 the physiological situation 428:454 As a consequence, assays to assess inhibition of lectin binding should necessarily come as close as possible to the physiological situation, to characterize an impact of a synthetic compound on biorelevant binding with pharmaceutical perspective. 28013366 0 37 theme synthetic 11:19 arg1 chemistry 21:29 synthetic chemistry 11:29 synthetic chemistry 11:29 Teaming up synthetic chemistry and histochemistry for activity screening in galectin-directed inhibitor design. 28013366 4 38 theme lactosides 840:849 arg1 pairs 821:825 Six pairs 817:825 Six pairs of synthetic lactosides from tailoring of the headgroup (3'-O-sulfation) and the aglycone (β-methyl to aromatic S- and O-linked extensions) as well as three bi- to tetravalent glycoclusters 817:1015 Six pairs of synthetic lactosides from tailoring of the headgroup (3'-O-sulfation) and the aglycone (β-methyl to aromatic S- and O-linked extensions) as well as three bi- to tetravalent glycoclusters were used as test compounds. 28013366 4 38 theme lactosides 840:849 arg1 compounds 1035:1043 test compounds 1030:1043 test compounds 1030:1043 Six pairs of synthetic lactosides from tailoring of the headgroup (3'-O-sulfation) and the aglycone (β-methyl to aromatic S- and O-linked extensions) as well as three bi- to tetravalent glycoclusters were used as test compounds. 28013366 7 39 theme other 1548:1552 arg1 cells/tissues 1554:1566 other cells/tissues 1548:1566 other cells/tissues 1548:1566 The experiments revealed cell/tissue binding of galectin-8 preferentially via one domain, depending on the cell type so that the effect of an inhibitor in a certain context cannot be extrapolated to other cells/tissues. 28013366 8 40 theme other 1597:1601 arg1 galectins 1603:1611 the other galectins 1593:1611 the other galectins 1593:1611 Moreover, the work with the other galectins attests that this assay enables comprehensive analysis of the galectin network in serial tissue sections to determine overlaps and regional differences in inhibitory profiles. 28013366 8 41 theme galectin 1675:1682 arg1 network 1684:1690 the galectin network 1671:1690 the galectin network in serial tissue sections 1671:1716 Moreover, the work with the other galectins attests that this assay enables comprehensive analysis of the galectin network in serial tissue sections to determine overlaps and regional differences in inhibitory profiles. 28013366 4 42 link O-linked 946:953 arg1 extensions 955:964 O-linked extensions 946:964 O-linked extensions 946:964 Six pairs of synthetic lactosides from tailoring of the headgroup (3'-O-sulfation) and the aglycone (β-methyl to aromatic S- and O-linked extensions) as well as three bi- to tetravalent glycoclusters were used as test compounds. 28013366 3 43 theme adhesion/growth-regulatory 693:718 arg1 galectins 720:728 labeled adhesion/growth-regulatory galectins 685:728 labeled adhesion/growth-regulatory galectins 685:728 We here introduce in a proof-of-principle manner work with sections of paraffin-embedded tissue (jejunum, epididymis) and labeled adhesion/growth-regulatory galectins, harboring one (galectin-1 and galectin-3) or two (galectin-8) types of lectin domain. 28013366 7 44 theme certain 1506:1512 arg1 context 1514:1520 a certain context 1504:1520 a certain context 1504:1520 The experiments revealed cell/tissue binding of galectin-8 preferentially via one domain, depending on the cell type so that the effect of an inhibitor in a certain context cannot be extrapolated to other cells/tissues. 28013366 1 45 theme glycolipids 303:313 arg1 abundance 263:271 the natural abundance 251:271 the natural abundance of cellular glycoproteins and glycolipids 251:313 A hallmark of endogenous lectins is their ability to select a few distinct glycoconjugates as counterreceptors for functional pairing from the natural abundance of cellular glycoproteins and glycolipids. 28013366 2 46 theme binding 372:378 arg1 inhibition 351:360 inhibition 351:360 inhibition of lectin binding 351:378 As a consequence, assays to assess inhibition of lectin binding should necessarily come as close as possible to the physiological situation, to characterize an impact of a synthetic compound on biorelevant binding with pharmaceutical perspective. 28013366 8 47 theme tissue 1702:1707 arg1 sections 1709:1716 serial tissue sections 1695:1716 serial tissue sections 1695:1716 Moreover, the work with the other galectins attests that this assay enables comprehensive analysis of the galectin network in serial tissue sections to determine overlaps and regional differences in inhibitory profiles. 28013366 8 48 theme comprehensive 1645:1657 arg1 analysis 1659:1666 comprehensive analysis 1645:1666 comprehensive analysis of the galectin network in serial tissue sections 1645:1716 Moreover, the work with the other galectins attests that this assay enables comprehensive analysis of the galectin network in serial tissue sections to determine overlaps and regional differences in inhibitory profiles. 28013366 1 49 theme cellular 276:283 arg1 glycoproteins 285:297 cellular glycoproteins 276:297 cellular glycoproteins 276:297 A hallmark of endogenous lectins is their ability to select a few distinct glycoconjugates as counterreceptors for functional pairing from the natural abundance of cellular glycoproteins and glycolipids. 28013366 0 50 from screening 63:71 arg1 design 104:109 galectin-directed inhibitor design 76:109 galectin-directed inhibitor design 76:109 Teaming up synthetic chemistry and histochemistry for activity screening in galectin-directed inhibitor design. 28013366 0 51 theme galectin-directed 76:92 arg1 design 104:109 galectin-directed inhibitor design 76:109 galectin-directed inhibitor design 76:109 Teaming up synthetic chemistry and histochemistry for activity screening in galectin-directed inhibitor design. 28013366 6 52 theme similar 1287:1293 arg1 grading 1295:1301 similar grading 1287:1301 similar grading 1287:1301 Flanking cytofluorimetric assays on lectin binding to native cells gave similar grading, excluding a major impact of tissue fixation. 28013366 3 53 theme proof-of-principle 586:603 arg1 manner 605:610 a proof-of-principle manner 584:610 a proof-of-principle manner 584:610 We here introduce in a proof-of-principle manner work with sections of paraffin-embedded tissue (jejunum, epididymis) and labeled adhesion/growth-regulatory galectins, harboring one (galectin-1 and galectin-3) or two (galectin-8) types of lectin domain. 28013366 8 54 theme regional 1744:1751 arg1 differences 1753:1763 regional differences 1744:1763 regional differences in inhibitory profiles 1744:1786 Moreover, the work with the other galectins attests that this assay enables comprehensive analysis of the galectin network in serial tissue sections to determine overlaps and regional differences in inhibitory profiles. 28013366 1 55 theme distinct 178:185 arg1 glycoconjugates 187:201 a few distinct glycoconjugates 172:201 a few distinct glycoconjugates as counterreceptors for functional pairing from the natural abundance of cellular glycoproteins and glycolipids 172:313 A hallmark of endogenous lectins is their ability to select a few distinct glycoconjugates as counterreceptors for functional pairing from the natural abundance of cellular glycoproteins and glycolipids. 28013366 4 56 theme headgroup 873:881 arg1 tailoring 856:864 tailoring 856:864 tailoring of the headgroup (3'-O-sulfation) and the aglycone (β-methyl to aromatic S- and O-linked extensions) as well as three bi- to tetravalent glycoclusters 856:1015 Six pairs of synthetic lactosides from tailoring of the headgroup (3'-O-sulfation) and the aglycone (β-methyl to aromatic S- and O-linked extensions) as well as three bi- to tetravalent glycoclusters were used as test compounds. 28013366 7 57 theme cell 1456:1459 arg1 type 1461:1464 the cell type 1452:1464 the cell type so that the effect of an inhibitor in a certain context cannot be extrapolated to other cells/tissues 1452:1566 The experiments revealed cell/tissue binding of galectin-8 preferentially via one domain, depending on the cell type so that the effect of an inhibitor in a certain context cannot be extrapolated to other cells/tissues. 28013366 4 58 theme aromatic 930:937 arg1 S- 939:940 aromatic S- 930:940 aromatic S- 930:940 Six pairs of synthetic lactosides from tailoring of the headgroup (3'-O-sulfation) and the aglycone (β-methyl to aromatic S- and O-linked extensions) as well as three bi- to tetravalent glycoclusters were used as test compounds. 28013366 1 59 from abundance 263:271 arg1 pairing 238:244 functional pairing 227:244 functional pairing from the natural abundance of cellular glycoproteins and glycolipids 227:313 A hallmark of endogenous lectins is their ability to select a few distinct glycoconjugates as counterreceptors for functional pairing from the natural abundance of cellular glycoproteins and glycolipids. 28013366 5 60 theme staining 1078:1085 arg1 intensity 1087:1095 staining intensity 1078:1095 staining intensity 1078:1095 Varying extents of reduction in staining intensity by synthetic compounds relative to unsubstituted/free lactose proved the applicability and sensitivity of the method. 28013366 6 61 theme native 1269:1274 arg1 cells 1276:1280 native cells 1269:1280 native cells 1269:1280 Flanking cytofluorimetric assays on lectin binding to native cells gave similar grading, excluding a major impact of tissue fixation. 28013366 3 62 theme domain 809:814 arg1 types 793:797 types 793:797 types of lectin domain 793:814 We here introduce in a proof-of-principle manner work with sections of paraffin-embedded tissue (jejunum, epididymis) and labeled adhesion/growth-regulatory galectins, harboring one (galectin-1 and galectin-3) or two (galectin-8) types of lectin domain. 28013366 4 63 theme aglycone 908:915 arg1 tailoring 856:864 tailoring 856:864 tailoring of the headgroup (3'-O-sulfation) and the aglycone (β-methyl to aromatic S- and O-linked extensions) as well as three bi- to tetravalent glycoclusters 856:1015 Six pairs of synthetic lactosides from tailoring of the headgroup (3'-O-sulfation) and the aglycone (β-methyl to aromatic S- and O-linked extensions) as well as three bi- to tetravalent glycoclusters were used as test compounds. 28013366 6 64 theme tissue 1332:1337 arg1 fixation 1339:1346 tissue fixation 1332:1346 tissue fixation 1332:1346 Flanking cytofluorimetric assays on lectin binding to native cells gave similar grading, excluding a major impact of tissue fixation. 28013366 1 65 theme lectins 137:143 arg1 ability 154:160 their ability to select a few distinct glycoconjugates as counterreceptors for functional pairing from the natural abundance of cellular glycoproteins and glycolipids 148:313 their ability to select a few distinct glycoconjugates as counterreceptors for functional pairing from the natural abundance of cellular glycoproteins and glycolipids 148:313 A hallmark of endogenous lectins is their ability to select a few distinct glycoconjugates as counterreceptors for functional pairing from the natural abundance of cellular glycoproteins and glycolipids. 28013366 1 65 theme lectins 137:143 arg1 hallmark 114:121 A hallmark 112:121 A hallmark of endogenous lectins 112:143 A hallmark of endogenous lectins is their ability to select a few distinct glycoconjugates as counterreceptors for functional pairing from the natural abundance of cellular glycoproteins and glycolipids. 28013366 5 66 theme reduction 1065:1073 arg1 extents 1054:1060 Varying extents 1046:1060 Varying extents of reduction in staining intensity by synthetic compounds relative to unsubstituted/free lactose 1046:1157 Varying extents of reduction in staining intensity by synthetic compounds relative to unsubstituted/free lactose proved the applicability and sensitivity of the method. 28013366 3 67 theme paraffin-embedded 634:650 arg1 tissue 652:657 paraffin-embedded tissue 634:657 paraffin-embedded tissue (jejunum, epididymis) 634:679 We here introduce in a proof-of-principle manner work with sections of paraffin-embedded tissue (jejunum, epididymis) and labeled adhesion/growth-regulatory galectins, harboring one (galectin-1 and galectin-3) or two (galectin-8) types of lectin domain. 28013366 4 68 from pairs 821:825 arg1 tailoring 856:864 tailoring 856:864 tailoring of the headgroup (3'-O-sulfation) and the aglycone (β-methyl to aromatic S- and O-linked extensions) as well as three bi- to tetravalent glycoclusters 856:1015 Six pairs of synthetic lactosides from tailoring of the headgroup (3'-O-sulfation) and the aglycone (β-methyl to aromatic S- and O-linked extensions) as well as three bi- to tetravalent glycoclusters were used as test compounds. 28013366 6 69 theme cytofluorimetric 1224:1239 arg1 assays 1241:1246 Flanking cytofluorimetric assays 1215:1246 Flanking cytofluorimetric assays on lectin binding to native cells 1215:1280 Flanking cytofluorimetric assays on lectin binding to native cells gave similar grading, excluding a major impact of tissue fixation. 28013366 6 70 from assays 1241:1246 arg1 binding 1258:1264 lectin binding 1251:1264 lectin binding to native cells 1251:1280 Flanking cytofluorimetric assays on lectin binding to native cells gave similar grading, excluding a major impact of tissue fixation. 28013366 0 71 theme inhibitor 94:102 arg1 design 104:109 galectin-directed inhibitor design 76:109 galectin-directed inhibitor design 76:109 Teaming up synthetic chemistry and histochemistry for activity screening in galectin-directed inhibitor design. 28013366 2 72 theme synthetic 488:496 arg1 compound 498:505 a synthetic compound 486:505 a synthetic compound 486:505 As a consequence, assays to assess inhibition of lectin binding should necessarily come as close as possible to the physiological situation, to characterize an impact of a synthetic compound on biorelevant binding with pharmaceutical perspective. 28013366 5 73 from intensity 1087:1095 arg1 extents 1054:1060 Varying extents 1046:1060 Varying extents of reduction in staining intensity by synthetic compounds relative to unsubstituted/free lactose 1046:1157 Varying extents of reduction in staining intensity by synthetic compounds relative to unsubstituted/free lactose proved the applicability and sensitivity of the method. 28013366 2 74 theme pharmaceutical 535:548 arg1 perspective 550:560 pharmaceutical perspective 535:560 pharmaceutical perspective 535:560 As a consequence, assays to assess inhibition of lectin binding should necessarily come as close as possible to the physiological situation, to characterize an impact of a synthetic compound on biorelevant binding with pharmaceutical perspective. 28013366 2 75 from impact 476:481 arg1 binding 522:528 biorelevant binding 510:528 biorelevant binding with pharmaceutical perspective 510:560 As a consequence, assays to assess inhibition of lectin binding should necessarily come as close as possible to the physiological situation, to characterize an impact of a synthetic compound on biorelevant binding with pharmaceutical perspective. 28013366 4 76 used used 1022:1025 arg2 compounds 1035:1043 test compounds 1030:1043 test compounds 1030:1043 Six pairs of synthetic lactosides from tailoring of the headgroup (3'-O-sulfation) and the aglycone (β-methyl to aromatic S- and O-linked extensions) as well as three bi- to tetravalent glycoclusters were used as test compounds. 28013366 4 76 used used 1022:1025 arg2 pairs 821:825 Six pairs 817:825 Six pairs of synthetic lactosides from tailoring of the headgroup (3'-O-sulfation) and the aglycone (β-methyl to aromatic S- and O-linked extensions) as well as three bi- to tetravalent glycoclusters 817:1015 Six pairs of synthetic lactosides from tailoring of the headgroup (3'-O-sulfation) and the aglycone (β-methyl to aromatic S- and O-linked extensions) as well as three bi- to tetravalent glycoclusters were used as test compounds. 28013366 5 77 dep applicability 1170:1182 arg1 the 1166:1168 the 1166:1168 the 1166:1168 Varying extents of reduction in staining intensity by synthetic compounds relative to unsubstituted/free lactose proved the applicability and sensitivity of the method. 28013366 2 78 with binding 522:528 arg1 perspective 550:560 pharmaceutical perspective 535:560 pharmaceutical perspective 535:560 As a consequence, assays to assess inhibition of lectin binding should necessarily come as close as possible to the physiological situation, to characterize an impact of a synthetic compound on biorelevant binding with pharmaceutical perspective. 28013366 5 79 theme method 1207:1212 arg1 sensitivity 1188:1198 sensitivity 1188:1198 sensitivity 1188:1198 Varying extents of reduction in staining intensity by synthetic compounds relative to unsubstituted/free lactose proved the applicability and sensitivity of the method. 28013366 5 79 theme method 1207:1212 arg1 applicability 1170:1182 applicability 1170:1182 applicability 1170:1182 Varying extents of reduction in staining intensity by synthetic compounds relative to unsubstituted/free lactose proved the applicability and sensitivity of the method. 28013366 5 80 from extents 1054:1060 arg1 intensity 1087:1095 staining intensity 1078:1095 staining intensity 1078:1095 Varying extents of reduction in staining intensity by synthetic compounds relative to unsubstituted/free lactose proved the applicability and sensitivity of the method. 28013366 4 81 theme tetravalent 991:1001 arg1 glycoclusters 1003:1015 tetravalent glycoclusters 991:1015 tetravalent glycoclusters 991:1015 Six pairs of synthetic lactosides from tailoring of the headgroup (3'-O-sulfation) and the aglycone (β-methyl to aromatic S- and O-linked extensions) as well as three bi- to tetravalent glycoclusters were used as test compounds. 28013366 4 82 theme bi- 984:986 arg1 tailoring 856:864 tailoring 856:864 tailoring of the headgroup (3'-O-sulfation) and the aglycone (β-methyl to aromatic S- and O-linked extensions) as well as three bi- to tetravalent glycoclusters 856:1015 Six pairs of synthetic lactosides from tailoring of the headgroup (3'-O-sulfation) and the aglycone (β-methyl to aromatic S- and O-linked extensions) as well as three bi- to tetravalent glycoclusters were used as test compounds. 28013366 4 83 theme synthetic 830:838 arg1 lactosides 840:849 synthetic lactosides 830:849 synthetic lactosides from tailoring of the headgroup (3'-O-sulfation) and the aglycone (β-methyl to aromatic S- and O-linked extensions) as well as three bi- to tetravalent glycoclusters 830:1015 Six pairs of synthetic lactosides from tailoring of the headgroup (3'-O-sulfation) and the aglycone (β-methyl to aromatic S- and O-linked extensions) as well as three bi- to tetravalent glycoclusters were used as test compounds. 28013366 0 84 theme activity 54:61 arg1 screening 63:71 activity screening 54:71 activity screening in galectin-directed inhibitor design 54:109 Teaming up synthetic chemistry and histochemistry for activity screening in galectin-directed inhibitor design. 28013366 3 85 theme galectins 720:728 arg1 sections 622:629 sections 622:629 sections 622:629 We here introduce in a proof-of-principle manner work with sections of paraffin-embedded tissue (jejunum, epididymis) and labeled adhesion/growth-regulatory galectins, harboring one (galectin-1 and galectin-3) or two (galectin-8) types of lectin domain. 28013366 8 86 theme network 1684:1690 arg1 analysis 1659:1666 comprehensive analysis 1645:1666 comprehensive analysis of the galectin network in serial tissue sections 1645:1716 Moreover, the work with the other galectins attests that this assay enables comprehensive analysis of the galectin network in serial tissue sections to determine overlaps and regional differences in inhibitory profiles. 28013366 3 87 theme labeled 685:691 arg1 galectins 720:728 labeled adhesion/growth-regulatory galectins 685:728 labeled adhesion/growth-regulatory galectins 685:728 We here introduce in a proof-of-principle manner work with sections of paraffin-embedded tissue (jejunum, epididymis) and labeled adhesion/growth-regulatory galectins, harboring one (galectin-1 and galectin-3) or two (galectin-8) types of lectin domain. 28013366 8 88 theme serial 1695:1700 arg1 sections 1709:1716 serial tissue sections 1695:1716 serial tissue sections 1695:1716 Moreover, the work with the other galectins attests that this assay enables comprehensive analysis of the galectin network in serial tissue sections to determine overlaps and regional differences in inhibitory profiles. 28013366 1 89 theme natural 255:261 arg1 abundance 263:271 the natural abundance 251:271 the natural abundance of cellular glycoproteins and glycolipids 251:313 A hallmark of endogenous lectins is their ability to select a few distinct glycoconjugates as counterreceptors for functional pairing from the natural abundance of cellular glycoproteins and glycolipids. 27983978 7 0 theme primed 888:893 arg1 state 895:899 primed state 888:899 primed state 888:899 In the transition from naïve state to primed state, Ogt maintains cell survival, whereas Oga has no function. 27983978 1 1 theme mouse 119:123 arg1 ESCs 147:150 ESCs 147:150 ESCs 147:150 "Naïve" mouse embryonic stem cells (ESCs) are derived from pre-implantation embryos and possess pluripotency, the ability to differentiate into any cell type of the body. 27983978 1 1 theme mouse 119:123 arg1 cells 140:144 "Naïve" mouse embryonic stem cells 111:144 "Naïve" mouse embryonic stem cells (ESCs) 111:151 "Naïve" mouse embryonic stem cells (ESCs) are derived from pre-implantation embryos and possess pluripotency, the ability to differentiate into any cell type of the body. 27983978 0 2 theme cells 65:69 arg1 survival 29:36 the survival 25:36 the survival of primed pluripotent stem cells 25:69 O-GlcNAc is required for the survival of primed pluripotent stem cells and their reversion to the naïve state. 27983978 0 2 theme cells 65:69 arg1 reversion 81:89 their reversion 75:89 their reversion to the naïve state 75:108 O-GlcNAc is required for the survival of primed pluripotent stem cells and their reversion to the naïve state. 27983978 9 3 theme primed 1149:1154 arg1 ESD-EpiSCs 1156:1165 primed ESD-EpiSCs 1149:1165 primed ESD-EpiSCs 1149:1165 Here, we show that Ogt is required for the survival of primed ESD-EpiSCs. 27983978 5 4 attach removed 734:740 arg2 O-GlcNAc 631:638 O-GlcNAc 631:638 O-GlcNAc 631:638 O-GlcNAc is transferred to serine and threonine residues of proteins by O-GlcNAc transferase (Ogt) and removed from them by O-GlcNAcase (Oga). 27983978 5 4 attach removed 734:740 arg1 them 747:750 them 747:750 them 747:750 O-GlcNAc is transferred to serine and threonine residues of proteins by O-GlcNAc transferase (Ogt) and removed from them by O-GlcNAcase (Oga). 27983978 2 5 theme " 289:289 arg1 epiblast 297:304 "Primed" mouse epiblast 282:304 "Primed" mouse epiblast stem cells (EpiSCs) 282:324 "Primed" mouse epiblast stem cells (EpiSCs) are also pluripotent but are derived from post-implantation embryos. 27983978 9 6 theme ESD-EpiSCs 1156:1165 arg1 survival 1137:1144 the survival 1133:1144 the survival of primed ESD-EpiSCs 1133:1165 Here, we show that Ogt is required for the survival of primed ESD-EpiSCs. 27983978 3 7 link ESC-derived 395:405 arg1 ESD-EpiSCs 415:424 ESD-EpiSCs 415:424 ESD-EpiSCs 415:424 ESC-derived EpiSCs (ESD-EpiSCs) are "primed" pluripotent stem cells and can revert to naïve reverted ESCs (rESCs). 27983978 3 7 link ESC-derived 395:405 arg1 EpiSCs 407:412 ESC-derived EpiSCs 395:412 ESC-derived EpiSCs (ESD-EpiSCs) 395:425 ESC-derived EpiSCs (ESD-EpiSCs) are "primed" pluripotent stem cells and can revert to naïve reverted ESCs (rESCs). 27983978 11 8 theme naïve 1371:1375 arg1 rESCs 1377:1381 naïve rESCs 1371:1381 naïve rESCs 1371:1381 Furthermore, both Ogt and Oga were required for the reversion from primed ESD-EpiSCs to naïve rESCs. 27983978 2 9 theme mouse 291:295 arg1 epiblast 297:304 "Primed" mouse epiblast 282:304 "Primed" mouse epiblast stem cells (EpiSCs) 282:324 "Primed" mouse epiblast stem cells (EpiSCs) are also pluripotent but are derived from post-implantation embryos. 27983978 5 10 theme O-GlcNAc 703:710 arg1 Ogt 725:727 Ogt 725:727 Ogt 725:727 O-GlcNAc is transferred to serine and threonine residues of proteins by O-GlcNAc transferase (Ogt) and removed from them by O-GlcNAcase (Oga). 27983978 5 10 theme O-GlcNAc 703:710 arg1 transferase 712:722 O-GlcNAc transferase 703:722 O-GlcNAc transferase (Ogt) 703:728 O-GlcNAc is transferred to serine and threonine residues of proteins by O-GlcNAc transferase (Ogt) and removed from them by O-GlcNAcase (Oga). 27983978 10 11 from ESCs 1256:1259 arg1 induction 1235:1243 induction 1235:1243 induction from naïve ESCs to primed ESD-EpiSCs 1235:1280 The expression of cytosolic Oga was significantly increased during induction from naïve ESCs to primed ESD-EpiSCs. 27983978 10 12 theme naïve 1250:1254 arg1 ESCs 1256:1259 naïve ESCs 1250:1259 naïve ESCs 1250:1259 The expression of cytosolic Oga was significantly increased during induction from naïve ESCs to primed ESD-EpiSCs. 27983978 3 13 theme stem 452:455 arg1 cells 457:461 pluripotent stem cells 440:461 pluripotent stem cells 440:461 ESC-derived EpiSCs (ESD-EpiSCs) are "primed" pluripotent stem cells and can revert to naïve reverted ESCs (rESCs). 27983978 7 14 dep maintains 906:914 arg1 whereas 931:937 whereas 931:937 whereas 931:937 In the transition from naïve state to primed state, Ogt maintains cell survival, whereas Oga has no function. 27983978 1 15 theme stem 135:138 arg1 ESCs 147:150 ESCs 147:150 ESCs 147:150 "Naïve" mouse embryonic stem cells (ESCs) are derived from pre-implantation embryos and possess pluripotency, the ability to differentiate into any cell type of the body. 27983978 1 15 theme stem 135:138 arg1 cells 140:144 "Naïve" mouse embryonic stem cells 111:144 "Naïve" mouse embryonic stem cells (ESCs) 111:151 "Naïve" mouse embryonic stem cells (ESCs) are derived from pre-implantation embryos and possess pluripotency, the ability to differentiate into any cell type of the body. 27983978 8 16 theme primed 1049:1054 arg1 state 1056:1060 the primed state 1045:1060 the primed state 1045:1060 However, the function of O-GlcNAc in primed ESD-EpiSCs and during the reversion from the primed state to naïve rESCs remains unclear. 27983978 8 17 from function 973:980 arg1 ESD-EpiSCs 1004:1013 primed ESD-EpiSCs 997:1013 primed ESD-EpiSCs 997:1013 However, the function of O-GlcNAc in primed ESD-EpiSCs and during the reversion from the primed state to naïve rESCs remains unclear. 27983978 4 18 theme O-linked 510:517 arg1 modification 588:599 a posttranslational modification 568:599 a posttranslational modification in the cytoplasm and nucleus 568:628 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a posttranslational modification in the cytoplasm and nucleus. 27983978 4 18 theme O-linked 510:517 arg1 O-GlcNAcylation 548:562 O-GlcNAcylation 548:562 O-GlcNAcylation 548:562 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a posttranslational modification in the cytoplasm and nucleus. 27983978 4 18 theme O-linked 510:517 arg1 β-N-acetylglucosaminylation 519:545 O-linked β-N-acetylglucosaminylation 510:545 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) 510:563 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a posttranslational modification in the cytoplasm and nucleus. 27983978 4 19 theme posttranslational 570:586 arg1 modification 588:599 a posttranslational modification 568:599 a posttranslational modification in the cytoplasm and nucleus 568:628 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a posttranslational modification in the cytoplasm and nucleus. 27983978 4 19 theme posttranslational 570:586 arg1 β-N-acetylglucosaminylation 519:545 O-linked β-N-acetylglucosaminylation 510:545 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) 510:563 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a posttranslational modification in the cytoplasm and nucleus. 27983978 2 20 theme post-implantation 368:384 arg1 embryos 386:392 post-implantation embryos 368:392 post-implantation embryos 368:392 "Primed" mouse epiblast stem cells (EpiSCs) are also pluripotent but are derived from post-implantation embryos. 27983978 3 21 theme pluripotent 440:450 arg1 cells 457:461 pluripotent stem cells 440:461 pluripotent stem cells 440:461 ESC-derived EpiSCs (ESD-EpiSCs) are "primed" pluripotent stem cells and can revert to naïve reverted ESCs (rESCs). 27983978 3 22 theme naïve 481:485 arg1 rESCs 502:506 rESCs 502:506 rESCs 502:506 ESC-derived EpiSCs (ESD-EpiSCs) are "primed" pluripotent stem cells and can revert to naïve reverted ESCs (rESCs). 27983978 3 22 theme naïve 481:485 arg1 ESCs 496:499 naïve reverted ESCs 481:499 naïve reverted ESCs (rESCs) 481:507 ESC-derived EpiSCs (ESD-EpiSCs) are "primed" pluripotent stem cells and can revert to naïve reverted ESCs (rESCs). 27983978 8 23 theme O-GlcNAc 985:992 arg1 function 973:980 the function 969:980 the function of O-GlcNAc in primed ESD-EpiSCs and during the reversion from the primed state to naïve rESCs 969:1075 However, the function of O-GlcNAc in primed ESD-EpiSCs and during the reversion from the primed state to naïve rESCs remains unclear. 27983978 12 24 theme primed 1472:1477 arg1 ESD-EpiSCs 1479:1488 primed ESD-EpiSCs 1472:1488 primed ESD-EpiSCs 1472:1488 These findings indicate that O-GlcNAcylation plays an important role in the survival of primed ESD-EpiSCs and in their reversion to naïve rESCs. 27983978 3 25 theme reverted 487:494 arg1 rESCs 502:506 rESCs 502:506 rESCs 502:506 ESC-derived EpiSCs (ESD-EpiSCs) are "primed" pluripotent stem cells and can revert to naïve reverted ESCs (rESCs). 27983978 3 25 theme reverted 487:494 arg1 ESCs 496:499 naïve reverted ESCs 481:499 naïve reverted ESCs (rESCs) 481:507 ESC-derived EpiSCs (ESD-EpiSCs) are "primed" pluripotent stem cells and can revert to naïve reverted ESCs (rESCs). 27983978 12 26 theme ESD-EpiSCs 1479:1488 arg1 survival 1460:1467 the survival 1456:1467 the survival of primed ESD-EpiSCs 1456:1488 These findings indicate that O-GlcNAcylation plays an important role in the survival of primed ESD-EpiSCs and in their reversion to naïve rESCs. 27983978 2 27 attach derived 355:361 arg2 cells 311:315 "Primed" mouse epiblast stem cells 282:315 "Primed" mouse epiblast stem cells (EpiSCs) 282:324 "Primed" mouse epiblast stem cells (EpiSCs) are also pluripotent but are derived from post-implantation embryos. 27983978 2 27 attach derived 355:361 arg1 embryos 386:392 post-implantation embryos 368:392 post-implantation embryos 368:392 "Primed" mouse epiblast stem cells (EpiSCs) are also pluripotent but are derived from post-implantation embryos. 27983978 2 27 attach derived 355:361 arg2 EpiSCs 318:323 EpiSCs 318:323 EpiSCs 318:323 "Primed" mouse epiblast stem cells (EpiSCs) are also pluripotent but are derived from post-implantation embryos. 27983978 3 28 dep " 438:438 arg1 primed 432:437 primed 432:437 primed 432:437 ESC-derived EpiSCs (ESD-EpiSCs) are "primed" pluripotent stem cells and can revert to naïve reverted ESCs (rESCs). 27983978 7 29 theme naïve 873:877 arg1 state 879:883 naïve state 873:883 naïve state 873:883 In the transition from naïve state to primed state, Ogt maintains cell survival, whereas Oga has no function. 27983978 3 30 theme ESC-derived 395:405 arg1 ESD-EpiSCs 415:424 ESD-EpiSCs 415:424 ESD-EpiSCs 415:424 ESC-derived EpiSCs (ESD-EpiSCs) are "primed" pluripotent stem cells and can revert to naïve reverted ESCs (rESCs). 27983978 3 30 theme ESC-derived 395:405 arg1 EpiSCs 407:412 ESC-derived EpiSCs 395:412 ESC-derived EpiSCs (ESD-EpiSCs) 395:425 ESC-derived EpiSCs (ESD-EpiSCs) are "primed" pluripotent stem cells and can revert to naïve reverted ESCs (rESCs). 27983978 0 31 theme naïve 98:102 arg1 state 104:108 the naïve state 94:108 the naïve state 94:108 O-GlcNAc is required for the survival of primed pluripotent stem cells and their reversion to the naïve state. 27983978 6 32 theme naïve 777:781 arg1 ESCs 783:786 naïve ESCs 777:786 naïve ESCs 777:786 In naïve ESCs, O-GlcNAc contributes to maintain the undifferentiated state. 27983978 1 33 theme embryonic 125:133 arg1 ESCs 147:150 ESCs 147:150 ESCs 147:150 "Naïve" mouse embryonic stem cells (ESCs) are derived from pre-implantation embryos and possess pluripotency, the ability to differentiate into any cell type of the body. 27983978 1 33 theme embryonic 125:133 arg1 cells 140:144 "Naïve" mouse embryonic stem cells 111:144 "Naïve" mouse embryonic stem cells (ESCs) 111:151 "Naïve" mouse embryonic stem cells (ESCs) are derived from pre-implantation embryos and possess pluripotency, the ability to differentiate into any cell type of the body. 27983978 1 34 theme Naïve 112:116 arg1 ESCs 147:150 ESCs 147:150 ESCs 147:150 "Naïve" mouse embryonic stem cells (ESCs) are derived from pre-implantation embryos and possess pluripotency, the ability to differentiate into any cell type of the body. 27983978 1 34 theme Naïve 112:116 arg1 cells 140:144 "Naïve" mouse embryonic stem cells 111:144 "Naïve" mouse embryonic stem cells (ESCs) 111:151 "Naïve" mouse embryonic stem cells (ESCs) are derived from pre-implantation embryos and possess pluripotency, the ability to differentiate into any cell type of the body. 27983978 10 35 theme primed 1264:1269 arg1 ESD-EpiSCs 1271:1280 primed ESD-EpiSCs 1264:1280 primed ESD-EpiSCs 1264:1280 The expression of cytosolic Oga was significantly increased during induction from naïve ESCs to primed ESD-EpiSCs. 27983978 1 36 contain possess 199:205 arg1 ESCs 147:150 ESCs 147:150 ESCs 147:150 "Naïve" mouse embryonic stem cells (ESCs) are derived from pre-implantation embryos and possess pluripotency, the ability to differentiate into any cell type of the body. 27983978 1 36 contain possess 199:205 arg1 cells 140:144 "Naïve" mouse embryonic stem cells 111:144 "Naïve" mouse embryonic stem cells (ESCs) 111:151 "Naïve" mouse embryonic stem cells (ESCs) are derived from pre-implantation embryos and possess pluripotency, the ability to differentiate into any cell type of the body. 27983978 1 36 contain possess 199:205 arg2 pluripotency 207:218 pluripotency 207:218 pluripotency 207:218 "Naïve" mouse embryonic stem cells (ESCs) are derived from pre-implantation embryos and possess pluripotency, the ability to differentiate into any cell type of the body. 27983978 7 37 from state 879:883 arg1 transition 857:866 the transition 853:866 the transition from naïve state to primed state 853:899 In the transition from naïve state to primed state, Ogt maintains cell survival, whereas Oga has no function. 27983978 1 38 theme cell 259:262 arg1 type 264:267 any cell type 255:267 any cell type of the body 255:279 "Naïve" mouse embryonic stem cells (ESCs) are derived from pre-implantation embryos and possess pluripotency, the ability to differentiate into any cell type of the body. 27983978 4 39 link O-linked 510:517 arg1 modification 588:599 a posttranslational modification 568:599 a posttranslational modification in the cytoplasm and nucleus 568:628 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a posttranslational modification in the cytoplasm and nucleus. 27983978 4 39 link O-linked 510:517 arg1 O-GlcNAcylation 548:562 O-GlcNAcylation 548:562 O-GlcNAcylation 548:562 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a posttranslational modification in the cytoplasm and nucleus. 27983978 4 39 link O-linked 510:517 arg1 β-N-acetylglucosaminylation 519:545 O-linked β-N-acetylglucosaminylation 510:545 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) 510:563 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a posttranslational modification in the cytoplasm and nucleus. 27983978 12 40 theme naïve 1516:1520 arg1 rESCs 1522:1526 naïve rESCs 1516:1526 naïve rESCs 1516:1526 These findings indicate that O-GlcNAcylation plays an important role in the survival of primed ESD-EpiSCs and in their reversion to naïve rESCs. 27983978 7 41 theme cell 916:919 arg1 survival 921:928 cell survival 916:928 cell survival 916:928 In the transition from naïve state to primed state, Ogt maintains cell survival, whereas Oga has no function. 27983978 8 42 theme naïve 1065:1069 arg1 rESCs 1071:1075 naïve rESCs 1065:1075 naïve rESCs 1065:1075 However, the function of O-GlcNAc in primed ESD-EpiSCs and during the reversion from the primed state to naïve rESCs remains unclear. 27983978 0 43 theme primed 41:46 arg1 cells 65:69 primed pluripotent stem cells 41:69 primed pluripotent stem cells 41:69 O-GlcNAc is required for the survival of primed pluripotent stem cells and their reversion to the naïve state. 27983978 11 44 from ESD-EpiSCs 1357:1366 arg1 reversion 1335:1343 the reversion 1331:1343 the reversion from primed ESD-EpiSCs to naïve rESCs 1331:1381 Furthermore, both Ogt and Oga were required for the reversion from primed ESD-EpiSCs to naïve rESCs. 27983978 5 45 theme proteins 691:698 arg1 threonine 669:677 threonine 669:677 threonine 669:677 O-GlcNAc is transferred to serine and threonine residues of proteins by O-GlcNAc transferase (Ogt) and removed from them by O-GlcNAcase (Oga). 27983978 5 45 theme proteins 691:698 arg1 serine 658:663 serine 658:663 serine 658:663 O-GlcNAc is transferred to serine and threonine residues of proteins by O-GlcNAc transferase (Ogt) and removed from them by O-GlcNAcase (Oga). 27983978 2 46 theme Primed 283:288 arg1 epiblast 297:304 "Primed" mouse epiblast 282:304 "Primed" mouse epiblast stem cells (EpiSCs) 282:324 "Primed" mouse epiblast stem cells (EpiSCs) are also pluripotent but are derived from post-implantation embryos. 27983978 6 47 theme undifferentiated 826:841 arg1 state 843:847 the undifferentiated state 822:847 the undifferentiated state 822:847 In naïve ESCs, O-GlcNAc contributes to maintain the undifferentiated state. 27983978 8 48 from state 1056:1060 arg1 reversion 1030:1038 the reversion 1026:1038 the reversion from the primed state to naïve rESCs 1026:1075 However, the function of O-GlcNAc in primed ESD-EpiSCs and during the reversion from the primed state to naïve rESCs remains unclear. 27983978 10 49 theme Oga 1196:1198 arg1 expression 1172:1181 The expression 1168:1181 The expression of cytosolic Oga 1168:1198 The expression of cytosolic Oga was significantly increased during induction from naïve ESCs to primed ESD-EpiSCs. 27983978 11 50 theme primed 1350:1355 arg1 ESD-EpiSCs 1357:1366 primed ESD-EpiSCs 1350:1366 primed ESD-EpiSCs 1350:1366 Furthermore, both Ogt and Oga were required for the reversion from primed ESD-EpiSCs to naïve rESCs. 27983978 7 51 contain has 943:945 arg1 Oga 939:941 Oga 939:941 Oga 939:941 In the transition from naïve state to primed state, Ogt maintains cell survival, whereas Oga has no function. 27983978 7 51 contain has 943:945 arg2 function 950:957 no function 947:957 no function 947:957 In the transition from naïve state to primed state, Ogt maintains cell survival, whereas Oga has no function. 27983978 5 52 dep serine 658:663 arg1 residues 679:686 residues 679:686 residues 679:686 O-GlcNAc is transferred to serine and threonine residues of proteins by O-GlcNAc transferase (Ogt) and removed from them by O-GlcNAcase (Oga). 27983978 10 53 theme cytosolic 1186:1194 arg1 Oga 1196:1198 cytosolic Oga 1186:1198 cytosolic Oga 1186:1198 The expression of cytosolic Oga was significantly increased during induction from naïve ESCs to primed ESD-EpiSCs. 27983978 1 54 theme pre-implantation 170:185 arg1 embryos 187:193 pre-implantation embryos 170:193 pre-implantation embryos 170:193 "Naïve" mouse embryonic stem cells (ESCs) are derived from pre-implantation embryos and possess pluripotency, the ability to differentiate into any cell type of the body. 27983978 8 55 theme primed 997:1002 arg1 ESD-EpiSCs 1004:1013 primed ESD-EpiSCs 997:1013 primed ESD-EpiSCs 997:1013 However, the function of O-GlcNAc in primed ESD-EpiSCs and during the reversion from the primed state to naïve rESCs remains unclear. 27983978 1 56 theme " 117:117 arg1 ESCs 147:150 ESCs 147:150 ESCs 147:150 "Naïve" mouse embryonic stem cells (ESCs) are derived from pre-implantation embryos and possess pluripotency, the ability to differentiate into any cell type of the body. 27983978 1 56 theme " 117:117 arg1 cells 140:144 "Naïve" mouse embryonic stem cells 111:144 "Naïve" mouse embryonic stem cells (ESCs) 111:151 "Naïve" mouse embryonic stem cells (ESCs) are derived from pre-implantation embryos and possess pluripotency, the ability to differentiate into any cell type of the body. 27983978 4 57 from modification 588:599 arg1 nucleus 622:628 nucleus 622:628 nucleus 622:628 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a posttranslational modification in the cytoplasm and nucleus. 27983978 4 57 from modification 588:599 arg1 cytoplasm 608:616 cytoplasm 608:616 cytoplasm 608:616 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a posttranslational modification in the cytoplasm and nucleus. 27983978 0 58 theme stem 60:63 arg1 cells 65:69 primed pluripotent stem cells 41:69 primed pluripotent stem cells 41:69 O-GlcNAc is required for the survival of primed pluripotent stem cells and their reversion to the naïve state. 27983978 1 59 attach derived 157:163 arg2 ESCs 147:150 ESCs 147:150 ESCs 147:150 "Naïve" mouse embryonic stem cells (ESCs) are derived from pre-implantation embryos and possess pluripotency, the ability to differentiate into any cell type of the body. 27983978 1 59 attach derived 157:163 arg1 embryos 187:193 pre-implantation embryos 170:193 pre-implantation embryos 170:193 "Naïve" mouse embryonic stem cells (ESCs) are derived from pre-implantation embryos and possess pluripotency, the ability to differentiate into any cell type of the body. 27983978 1 59 attach derived 157:163 arg2 cells 140:144 "Naïve" mouse embryonic stem cells 111:144 "Naïve" mouse embryonic stem cells (ESCs) 111:151 "Naïve" mouse embryonic stem cells (ESCs) are derived from pre-implantation embryos and possess pluripotency, the ability to differentiate into any cell type of the body. 27983978 2 60 theme stem 306:309 arg1 EpiSCs 318:323 EpiSCs 318:323 EpiSCs 318:323 "Primed" mouse epiblast stem cells (EpiSCs) are also pluripotent but are derived from post-implantation embryos. 27983978 2 60 theme stem 306:309 arg1 cells 311:315 "Primed" mouse epiblast stem cells 282:315 "Primed" mouse epiblast stem cells (EpiSCs) 282:324 "Primed" mouse epiblast stem cells (EpiSCs) are also pluripotent but are derived from post-implantation embryos. 27983978 12 61 theme important 1438:1446 arg1 role 1448:1451 an important role 1435:1451 an important role 1435:1451 These findings indicate that O-GlcNAcylation plays an important role in the survival of primed ESD-EpiSCs and in their reversion to naïve rESCs. 27983978 0 62 theme pluripotent 48:58 arg1 cells 65:69 primed pluripotent stem cells 41:69 primed pluripotent stem cells 41:69 O-GlcNAc is required for the survival of primed pluripotent stem cells and their reversion to the naïve state. 27983978 1 63 theme body 276:279 arg1 type 264:267 any cell type 255:267 any cell type of the body 255:279 "Naïve" mouse embryonic stem cells (ESCs) are derived from pre-implantation embryos and possess pluripotency, the ability to differentiate into any cell type of the body. 27983978 2 64 theme epiblast 297:304 arg1 EpiSCs 318:323 EpiSCs 318:323 EpiSCs 318:323 "Primed" mouse epiblast stem cells (EpiSCs) are also pluripotent but are derived from post-implantation embryos. 27983978 2 64 theme epiblast 297:304 arg1 cells 311:315 "Primed" mouse epiblast stem cells 282:315 "Primed" mouse epiblast stem cells (EpiSCs) 282:324 "Primed" mouse epiblast stem cells (EpiSCs) are also pluripotent but are derived from post-implantation embryos. 26498820 5 0 theme equivalent 1022:1031 arg1 capacity 1045:1052 equivalent antioxidant capacity 1022:1052 equivalent antioxidant capacity 1022:1052 Its antioxidant activity was also confirmed using β-carotene bleaching by linoleic acid assay, reducing sugar test and trolox equivalent antioxidant capacity. 26498820 8 1 theme molecular 1448:1456 arg1 changes 1458:1464 histological and molecular changes 1431:1464 histological and molecular changes 1431:1464 These results were confirmed by the improvement of histological and molecular changes. 26498820 7 2 theme KBrO3-treated 1360:1372 arg1 mice 1374:1377 the KBrO3-treated mice 1356:1377 the KBrO3-treated mice 1356:1377 The coadministration of the red alga associated to the KBrO3 alleviated hepatotoxicity as monitored by the improvement of hepatic oxidative stress biomarkers and plasma biochemical parameters, when compared to the KBrO3-treated mice. 26498820 3 3 dep A. 705:706 arg1 corallinum 708:717 A. corallinum 705:717 A. corallinum 705:717 Then, A. corallinum was tested in vivo for its potential protective effects against damage caused by KBrO3 in mice models divided into four groups: controls, KBrO3, KBrO3 + A. corallinum, and A. corallinum. 26498820 9 4 theme hypercholesterolemia 1614:1633 arg1 risks 1635:1639 inflammation and hypercholesterolemia risks 1597:1639 inflammation and hypercholesterolemia risks 1597:1639 Treatment with A. corallinum prevented liver damage induced by KBrO3, thus protecting the body against free radicals and reducing inflammation and hypercholesterolemia risks. 26498820 9 5 theme liver 1506:1510 arg1 damage 1512:1517 liver damage 1506:1517 liver damage induced by KBrO3 1506:1534 Treatment with A. corallinum prevented liver damage induced by KBrO3, thus protecting the body against free radicals and reducing inflammation and hypercholesterolemia risks. 26498820 1 6 theme chemical 247:254 arg1 constituents 256:267 chemical constituents 247:267 chemical constituents of the marine red alga Alsidium corallinum (A. corallinum) 247:326 In the course of searching for hepatoprotective agents from natural sources, the protective effect of chemical constituents of the marine red alga Alsidium corallinum (A. corallinum) against potassium bromate (KBrO3)-induced liver damage in adult mice was investigated. 26498820 1 7 from damage 376:381 arg1 mice 392:395 adult mice 386:395 adult mice 386:395 In the course of searching for hepatoprotective agents from natural sources, the protective effect of chemical constituents of the marine red alga Alsidium corallinum (A. corallinum) against potassium bromate (KBrO3)-induced liver damage in adult mice was investigated. 26498820 1 8 theme potassium 336:344 arg1 bromate 346:352 potassium bromate 336:352 potassium bromate 336:352 In the course of searching for hepatoprotective agents from natural sources, the protective effect of chemical constituents of the marine red alga Alsidium corallinum (A. corallinum) against potassium bromate (KBrO3)-induced liver damage in adult mice was investigated. 26498820 3 9 theme mice 623:626 arg1 models 628:633 mice models 623:633 mice models divided into four groups: controls, KBrO3, KBrO3 + A. corallinum, and A. corallinum 623:717 Then, A. corallinum was tested in vivo for its potential protective effects against damage caused by KBrO3 in mice models divided into four groups: controls, KBrO3, KBrO3 + A. corallinum, and A. corallinum. 26498820 1 10 theme constituents 256:267 arg1 effect 237:242 the protective effect 222:242 the protective effect of chemical constituents of the marine red alga Alsidium corallinum (A. corallinum) against potassium bromate (KBrO3)-induced liver damage in adult mice 222:395 In the course of searching for hepatoprotective agents from natural sources, the protective effect of chemical constituents of the marine red alga Alsidium corallinum (A. corallinum) against potassium bromate (KBrO3)-induced liver damage in adult mice was investigated. 26498820 7 11 theme alga 1178:1181 arg1 coadministration 1150:1165 The coadministration 1146:1165 The coadministration of the red alga associated to the KBrO3 1146:1205 The coadministration of the red alga associated to the KBrO3 alleviated hepatotoxicity as monitored by the improvement of hepatic oxidative stress biomarkers and plasma biochemical parameters, when compared to the KBrO3-treated mice. 26498820 5 12 theme β-carotene 946:955 arg1 bleaching 957:965 β-carotene bleaching 946:965 β-carotene bleaching 946:965 Its antioxidant activity was also confirmed using β-carotene bleaching by linoleic acid assay, reducing sugar test and trolox equivalent antioxidant capacity. 26498820 9 13 dep prevented 1496:1504 arg1 reducing 1588:1595 reducing 1588:1595 reducing inflammation and hypercholesterolemia risks 1588:1639 Treatment with A. corallinum prevented liver damage induced by KBrO3, thus protecting the body against free radicals and reducing inflammation and hypercholesterolemia risks. 26498820 9 13 dep prevented 1496:1504 arg1 protecting 1542:1551 protecting 1542:1551 protecting the body against free radicals 1542:1582 Treatment with A. corallinum prevented liver damage induced by KBrO3, thus protecting the body against free radicals and reducing inflammation and hypercholesterolemia risks. 26498820 3 14 dep groups 653:658 arg1 A. 705:706 A. 705:706 A. 705:706 Then, A. corallinum was tested in vivo for its potential protective effects against damage caused by KBrO3 in mice models divided into four groups: controls, KBrO3, KBrO3 + A. corallinum, and A. corallinum. 26498820 3 14 dep groups 653:658 arg1 KBrO3 + 678:684 KBrO3 + 678:684 KBrO3 + 678:684 Then, A. corallinum was tested in vivo for its potential protective effects against damage caused by KBrO3 in mice models divided into four groups: controls, KBrO3, KBrO3 + A. corallinum, and A. corallinum. 26498820 3 14 dep groups 653:658 arg1 KBrO3 671:675 KBrO3 671:675 KBrO3 671:675 Then, A. corallinum was tested in vivo for its potential protective effects against damage caused by KBrO3 in mice models divided into four groups: controls, KBrO3, KBrO3 + A. corallinum, and A. corallinum. 26498820 3 14 dep groups 653:658 arg1 controls 661:668 controls 661:668 controls 661:668 Then, A. corallinum was tested in vivo for its potential protective effects against damage caused by KBrO3 in mice models divided into four groups: controls, KBrO3, KBrO3 + A. corallinum, and A. corallinum. 26498820 7 15 theme red 1174:1176 arg1 alga 1178:1181 the red alga 1170:1181 the red alga associated to the KBrO3 1170:1205 The coadministration of the red alga associated to the KBrO3 alleviated hepatotoxicity as monitored by the improvement of hepatic oxidative stress biomarkers and plasma biochemical parameters, when compared to the KBrO3-treated mice. 26498820 1 16 dep A. 313:314 arg1 corallinum 316:325 A. corallinum 313:325 A. corallinum 313:325 In the course of searching for hepatoprotective agents from natural sources, the protective effect of chemical constituents of the marine red alga Alsidium corallinum (A. corallinum) against potassium bromate (KBrO3)-induced liver damage in adult mice was investigated. 26498820 0 17 theme potassium 107:115 arg1 bromate 117:123 potassium bromate 107:123 potassium bromate in the mouse liver 107:142 Biological properties of Alsidium corallinum and its potential protective effects against damage caused by potassium bromate in the mouse liver. 26498820 2 18 theme in 419:420 arg1 properties 458:467 The in vitro antioxidant and antibacterial properties 415:467 The in vitro antioxidant and antibacterial properties of A. corallinum 415:484 The in vitro antioxidant and antibacterial properties of A. corallinum were firstly investigated. 26498820 1 19 theme searching 162:170 arg1 course 152:157 the course 148:157 the course of searching for hepatoprotective agents from natural sources 148:219 In the course of searching for hepatoprotective agents from natural sources, the protective effect of chemical constituents of the marine red alga Alsidium corallinum (A. corallinum) against potassium bromate (KBrO3)-induced liver damage in adult mice was investigated. 26498820 2 20 theme antibacterial 444:456 arg1 properties 458:467 The in vitro antioxidant and antibacterial properties 415:467 The in vitro antioxidant and antibacterial properties of A. corallinum 415:484 The in vitro antioxidant and antibacterial properties of A. corallinum were firstly investigated. 26498820 7 21 theme stress 1286:1291 arg1 biomarkers 1293:1302 hepatic oxidative stress biomarkers 1268:1302 hepatic oxidative stress biomarkers 1268:1302 The coadministration of the red alga associated to the KBrO3 alleviated hepatotoxicity as monitored by the improvement of hepatic oxidative stress biomarkers and plasma biochemical parameters, when compared to the KBrO3-treated mice. 26498820 7 22 theme biochemical 1315:1325 arg1 parameters 1327:1336 plasma biochemical parameters 1308:1336 plasma biochemical parameters 1308:1336 The coadministration of the red alga associated to the KBrO3 alleviated hepatotoxicity as monitored by the improvement of hepatic oxidative stress biomarkers and plasma biochemical parameters, when compared to the KBrO3-treated mice. 26498820 0 23 theme Biological 0:9 arg1 properties 11:20 Biological properties 0:20 Biological properties of Alsidium corallinum 0:43 Biological properties of Alsidium corallinum and its potential protective effects against damage caused by potassium bromate in the mouse liver. 26498820 2 24 dep in 419:420 arg1 vitro 422:426 vitro 422:426 vitro 422:426 The in vitro antioxidant and antibacterial properties of A. corallinum were firstly investigated. 26498820 0 25 from bromate 117:123 arg1 liver 138:142 the mouse liver 128:142 the mouse liver 128:142 Biological properties of Alsidium corallinum and its potential protective effects against damage caused by potassium bromate in the mouse liver. 26498820 1 26 theme hepatoprotective 176:191 arg1 agents 193:198 hepatoprotective agents 176:198 hepatoprotective agents from natural sources 176:219 In the course of searching for hepatoprotective agents from natural sources, the protective effect of chemical constituents of the marine red alga Alsidium corallinum (A. corallinum) against potassium bromate (KBrO3)-induced liver damage in adult mice was investigated. 26498820 0 27 theme Alsidium 25:32 arg1 corallinum 34:43 Alsidium corallinum 25:43 Alsidium corallinum 25:43 Biological properties of Alsidium corallinum and its potential protective effects against damage caused by potassium bromate in the mouse liver. 26498820 1 28 theme marine 276:281 arg1 alga 287:290 the marine red alga 272:290 the marine red alga Alsidium corallinum (A. corallinum) 272:326 In the course of searching for hepatoprotective agents from natural sources, the protective effect of chemical constituents of the marine red alga Alsidium corallinum (A. corallinum) against potassium bromate (KBrO3)-induced liver damage in adult mice was investigated. 26498820 1 28 theme marine 276:281 arg1 A. 313:314 A. 313:314 A. 313:314 In the course of searching for hepatoprotective agents from natural sources, the protective effect of chemical constituents of the marine red alga Alsidium corallinum (A. corallinum) against potassium bromate (KBrO3)-induced liver damage in adult mice was investigated. 26498820 6 29 theme tested 1129:1134 arg1 bacteria 1136:1143 the tested bacteria 1125:1143 the tested bacteria 1125:1143 The ethanolic extract of A. corallinum also showed good inhibition of the tested bacteria. 26498820 4 30 theme corallinum 772:781 arg1 composition 754:764 the rich composition 745:764 the rich composition of A. corallinum in antioxidant compounds like phenolics, flavonoids, anthocyanins, polysaccharides, chlorophyll and carotenoids 745:893 Our results demonstrated the rich composition of A. corallinum in antioxidant compounds like phenolics, flavonoids, anthocyanins, polysaccharides, chlorophyll and carotenoids. 26498820 5 31 dep assay 984:988 arg1 capacity 1045:1052 equivalent antioxidant capacity 1022:1052 equivalent antioxidant capacity 1022:1052 Its antioxidant activity was also confirmed using β-carotene bleaching by linoleic acid assay, reducing sugar test and trolox equivalent antioxidant capacity. 26498820 6 32 theme bacteria 1136:1143 arg1 inhibition 1111:1120 good inhibition 1106:1120 good inhibition of the tested bacteria 1106:1143 The ethanolic extract of A. corallinum also showed good inhibition of the tested bacteria. 26498820 1 33 theme red 283:285 arg1 alga 287:290 the marine red alga 272:290 the marine red alga Alsidium corallinum (A. corallinum) 272:326 In the course of searching for hepatoprotective agents from natural sources, the protective effect of chemical constituents of the marine red alga Alsidium corallinum (A. corallinum) against potassium bromate (KBrO3)-induced liver damage in adult mice was investigated. 26498820 1 33 theme red 283:285 arg1 A. 313:314 A. 313:314 A. 313:314 In the course of searching for hepatoprotective agents from natural sources, the protective effect of chemical constituents of the marine red alga Alsidium corallinum (A. corallinum) against potassium bromate (KBrO3)-induced liver damage in adult mice was investigated. 26498820 1 34 theme -induced 361:368 arg1 damage 376:381 potassium bromate (KBrO3)-induced liver damage 336:381 potassium bromate (KBrO3)-induced liver damage in adult mice 336:395 In the course of searching for hepatoprotective agents from natural sources, the protective effect of chemical constituents of the marine red alga Alsidium corallinum (A. corallinum) against potassium bromate (KBrO3)-induced liver damage in adult mice was investigated. 26498820 9 35 theme inflammation 1597:1608 arg1 risks 1635:1639 inflammation and hypercholesterolemia risks 1597:1639 inflammation and hypercholesterolemia risks 1597:1639 Treatment with A. corallinum prevented liver damage induced by KBrO3, thus protecting the body against free radicals and reducing inflammation and hypercholesterolemia risks. 26498820 7 36 theme plasma 1308:1313 arg1 parameters 1327:1336 plasma biochemical parameters 1308:1336 plasma biochemical parameters 1308:1336 The coadministration of the red alga associated to the KBrO3 alleviated hepatotoxicity as monitored by the improvement of hepatic oxidative stress biomarkers and plasma biochemical parameters, when compared to the KBrO3-treated mice. 26498820 1 37 theme alga 287:290 arg1 constituents 256:267 chemical constituents 247:267 chemical constituents of the marine red alga Alsidium corallinum (A. corallinum) 247:326 In the course of searching for hepatoprotective agents from natural sources, the protective effect of chemical constituents of the marine red alga Alsidium corallinum (A. corallinum) against potassium bromate (KBrO3)-induced liver damage in adult mice was investigated. 26498820 1 38 theme liver 370:374 arg1 damage 376:381 potassium bromate (KBrO3)-induced liver damage 336:381 potassium bromate (KBrO3)-induced liver damage in adult mice 336:395 In the course of searching for hepatoprotective agents from natural sources, the protective effect of chemical constituents of the marine red alga Alsidium corallinum (A. corallinum) against potassium bromate (KBrO3)-induced liver damage in adult mice was investigated. 26498820 3 39 theme protective 570:579 arg1 effects 581:587 its potential protective effects 556:587 its potential protective effects 556:587 Then, A. corallinum was tested in vivo for its potential protective effects against damage caused by KBrO3 in mice models divided into four groups: controls, KBrO3, KBrO3 + A. corallinum, and A. corallinum. 26498820 7 40 theme parameters 1327:1336 arg1 improvement 1253:1263 the improvement 1249:1263 the improvement of hepatic oxidative stress biomarkers and plasma biochemical parameters 1249:1336 The coadministration of the red alga associated to the KBrO3 alleviated hepatotoxicity as monitored by the improvement of hepatic oxidative stress biomarkers and plasma biochemical parameters, when compared to the KBrO3-treated mice. 26498820 1 41 theme natural 205:211 arg1 sources 213:219 natural sources 205:219 natural sources 205:219 In the course of searching for hepatoprotective agents from natural sources, the protective effect of chemical constituents of the marine red alga Alsidium corallinum (A. corallinum) against potassium bromate (KBrO3)-induced liver damage in adult mice was investigated. 26498820 0 42 theme corallinum 34:43 arg1 properties 11:20 Biological properties 0:20 Biological properties of Alsidium corallinum 0:43 Biological properties of Alsidium corallinum and its potential protective effects against damage caused by potassium bromate in the mouse liver. 26498820 0 42 theme corallinum 34:43 arg1 effects 74:80 its potential protective effects 49:80 its potential protective effects against damage 49:95 Biological properties of Alsidium corallinum and its potential protective effects against damage caused by potassium bromate in the mouse liver. 26498820 0 43 theme mouse 132:136 arg1 liver 138:142 the mouse liver 128:142 the mouse liver 128:142 Biological properties of Alsidium corallinum and its potential protective effects against damage caused by potassium bromate in the mouse liver. 26498820 1 44 dep -induced 361:368 arg1 bromate 346:352 potassium bromate 336:352 potassium bromate 336:352 In the course of searching for hepatoprotective agents from natural sources, the protective effect of chemical constituents of the marine red alga Alsidium corallinum (A. corallinum) against potassium bromate (KBrO3)-induced liver damage in adult mice was investigated. 26498820 8 45 theme changes 1458:1464 arg1 improvement 1416:1426 the improvement 1412:1426 the improvement of histological and molecular changes 1412:1464 These results were confirmed by the improvement of histological and molecular changes. 26498820 5 46 theme reducing 991:998 arg1 test 1006:1009 reducing sugar test 991:1009 reducing sugar test 991:1009 Its antioxidant activity was also confirmed using β-carotene bleaching by linoleic acid assay, reducing sugar test and trolox equivalent antioxidant capacity. 26498820 0 47 theme potential 53:61 arg1 effects 74:80 its potential protective effects 49:80 its potential protective effects against damage 49:95 Biological properties of Alsidium corallinum and its potential protective effects against damage caused by potassium bromate in the mouse liver. 26498820 3 48 from KBrO3 614:618 arg1 models 628:633 mice models 623:633 mice models divided into four groups: controls, KBrO3, KBrO3 + A. corallinum, and A. corallinum 623:717 Then, A. corallinum was tested in vivo for its potential protective effects against damage caused by KBrO3 in mice models divided into four groups: controls, KBrO3, KBrO3 + A. corallinum, and A. corallinum. 26498820 2 49 theme corallinum 475:484 arg1 properties 458:467 The in vitro antioxidant and antibacterial properties 415:467 The in vitro antioxidant and antibacterial properties of A. corallinum 415:484 The in vitro antioxidant and antibacterial properties of A. corallinum were firstly investigated. 26498820 4 50 theme antioxidant 786:796 arg1 compounds 798:806 antioxidant compounds 786:806 antioxidant compounds like phenolics, flavonoids, anthocyanins, polysaccharides, chlorophyll and carotenoids 786:893 Our results demonstrated the rich composition of A. corallinum in antioxidant compounds like phenolics, flavonoids, anthocyanins, polysaccharides, chlorophyll and carotenoids. 26498820 1 51 from sources 213:219 arg1 agents 193:198 hepatoprotective agents 176:198 hepatoprotective agents from natural sources 176:219 In the course of searching for hepatoprotective agents from natural sources, the protective effect of chemical constituents of the marine red alga Alsidium corallinum (A. corallinum) against potassium bromate (KBrO3)-induced liver damage in adult mice was investigated. 26498820 7 52 theme hepatic 1268:1274 arg1 biomarkers 1293:1302 hepatic oxidative stress biomarkers 1268:1302 hepatic oxidative stress biomarkers 1268:1302 The coadministration of the red alga associated to the KBrO3 alleviated hepatotoxicity as monitored by the improvement of hepatic oxidative stress biomarkers and plasma biochemical parameters, when compared to the KBrO3-treated mice. 26498820 2 53 theme antioxidant 428:438 arg1 properties 458:467 The in vitro antioxidant and antibacterial properties 415:467 The in vitro antioxidant and antibacterial properties of A. corallinum 415:484 The in vitro antioxidant and antibacterial properties of A. corallinum were firstly investigated. 26498820 9 54 with Treatment 1467:1475 arg1 corallinum 1485:1494 A. corallinum 1482:1494 A. corallinum 1482:1494 Treatment with A. corallinum prevented liver damage induced by KBrO3, thus protecting the body against free radicals and reducing inflammation and hypercholesterolemia risks. 26498820 1 55 theme adult 386:390 arg1 mice 392:395 adult mice 386:395 adult mice 386:395 In the course of searching for hepatoprotective agents from natural sources, the protective effect of chemical constituents of the marine red alga Alsidium corallinum (A. corallinum) against potassium bromate (KBrO3)-induced liver damage in adult mice was investigated. 26498820 3 56 theme potential 560:568 arg1 effects 581:587 its potential protective effects 556:587 its potential protective effects 556:587 Then, A. corallinum was tested in vivo for its potential protective effects against damage caused by KBrO3 in mice models divided into four groups: controls, KBrO3, KBrO3 + A. corallinum, and A. corallinum. 26498820 3 57 dep A. 519:520 arg1 corallinum 522:531 A. corallinum 519:531 A. corallinum 519:531 Then, A. corallinum was tested in vivo for its potential protective effects against damage caused by KBrO3 in mice models divided into four groups: controls, KBrO3, KBrO3 + A. corallinum, and A. corallinum. 26498820 8 58 theme histological 1431:1442 arg1 changes 1458:1464 histological and molecular changes 1431:1464 histological and molecular changes 1431:1464 These results were confirmed by the improvement of histological and molecular changes. 26498820 5 59 theme linoleic 970:977 arg1 acid 979:982 linoleic acid 970:982 linoleic acid assay 970:988 Its antioxidant activity was also confirmed using β-carotene bleaching by linoleic acid assay, reducing sugar test and trolox equivalent antioxidant capacity. 26498820 4 60 theme rich 749:752 arg1 composition 754:764 the rich composition 745:764 the rich composition of A. corallinum in antioxidant compounds like phenolics, flavonoids, anthocyanins, polysaccharides, chlorophyll and carotenoids 745:893 Our results demonstrated the rich composition of A. corallinum in antioxidant compounds like phenolics, flavonoids, anthocyanins, polysaccharides, chlorophyll and carotenoids. 26498820 5 61 theme sugar 1000:1004 arg1 test 1006:1009 reducing sugar test 991:1009 reducing sugar test 991:1009 Its antioxidant activity was also confirmed using β-carotene bleaching by linoleic acid assay, reducing sugar test and trolox equivalent antioxidant capacity. 26498820 6 62 theme good 1106:1109 arg1 inhibition 1111:1120 good inhibition 1106:1120 good inhibition of the tested bacteria 1106:1143 The ethanolic extract of A. corallinum also showed good inhibition of the tested bacteria. 26498820 9 63 theme free 1570:1573 arg1 radicals 1575:1582 free radicals 1570:1582 free radicals 1570:1582 Treatment with A. corallinum prevented liver damage induced by KBrO3, thus protecting the body against free radicals and reducing inflammation and hypercholesterolemia risks. 26498820 5 64 theme antioxidant 1033:1043 arg1 capacity 1045:1052 equivalent antioxidant capacity 1022:1052 equivalent antioxidant capacity 1022:1052 Its antioxidant activity was also confirmed using β-carotene bleaching by linoleic acid assay, reducing sugar test and trolox equivalent antioxidant capacity. 26498820 5 65 theme acid 979:982 arg1 assay 984:988 linoleic acid assay 970:988 linoleic acid assay 970:988 Its antioxidant activity was also confirmed using β-carotene bleaching by linoleic acid assay, reducing sugar test and trolox equivalent antioxidant capacity. 26498820 5 66 theme antioxidant 900:910 arg1 activity 912:919 Its antioxidant activity 896:919 Its antioxidant activity 896:919 Its antioxidant activity was also confirmed using β-carotene bleaching by linoleic acid assay, reducing sugar test and trolox equivalent antioxidant capacity. 26498820 7 67 theme biomarkers 1293:1302 arg1 improvement 1253:1263 the improvement 1249:1263 the improvement of hepatic oxidative stress biomarkers and plasma biochemical parameters 1249:1336 The coadministration of the red alga associated to the KBrO3 alleviated hepatotoxicity as monitored by the improvement of hepatic oxidative stress biomarkers and plasma biochemical parameters, when compared to the KBrO3-treated mice. 26498820 4 68 from composition 754:764 arg1 compounds 798:806 antioxidant compounds 786:806 antioxidant compounds like phenolics, flavonoids, anthocyanins, polysaccharides, chlorophyll and carotenoids 786:893 Our results demonstrated the rich composition of A. corallinum in antioxidant compounds like phenolics, flavonoids, anthocyanins, polysaccharides, chlorophyll and carotenoids. 26498820 6 69 theme ethanolic 1059:1067 arg1 extract 1069:1075 The ethanolic extract 1055:1075 The ethanolic extract of A. corallinum 1055:1092 The ethanolic extract of A. corallinum also showed good inhibition of the tested bacteria. 26498820 1 70 theme protective 226:235 arg1 effect 237:242 the protective effect 222:242 the protective effect of chemical constituents of the marine red alga Alsidium corallinum (A. corallinum) against potassium bromate (KBrO3)-induced liver damage in adult mice 222:395 In the course of searching for hepatoprotective agents from natural sources, the protective effect of chemical constituents of the marine red alga Alsidium corallinum (A. corallinum) against potassium bromate (KBrO3)-induced liver damage in adult mice was investigated. 26498820 0 71 theme protective 63:72 arg1 effects 74:80 its potential protective effects 49:80 its potential protective effects against damage 49:95 Biological properties of Alsidium corallinum and its potential protective effects against damage caused by potassium bromate in the mouse liver. 26498820 7 72 theme oxidative 1276:1284 arg1 biomarkers 1293:1302 hepatic oxidative stress biomarkers 1268:1302 hepatic oxidative stress biomarkers 1268:1302 The coadministration of the red alga associated to the KBrO3 alleviated hepatotoxicity as monitored by the improvement of hepatic oxidative stress biomarkers and plasma biochemical parameters, when compared to the KBrO3-treated mice. 26498820 6 73 theme corallinum 1083:1092 arg1 extract 1069:1075 The ethanolic extract 1055:1075 The ethanolic extract of A. corallinum 1055:1092 The ethanolic extract of A. corallinum also showed good inhibition of the tested bacteria. 26498820 3 74 dep KBrO3 + 678:684 arg1 corallinum 689:698 KBrO3 + A. corallinum 678:698 KBrO3 + A. corallinum 678:698 Then, A. corallinum was tested in vivo for its potential protective effects against damage caused by KBrO3 in mice models divided into four groups: controls, KBrO3, KBrO3 + A. corallinum, and A. corallinum. 26446095 4 0 theme cardiovascular 854:867 arg1 remodelling 869:879 cardiovascular remodelling 854:879 cardiovascular remodelling 854:879 RESULTS H rats developed visceral obesity, hypertension, insulin resistance, cardiovascular remodelling and fatty liver. 26446095 3 1 from diet 656:659 arg1 groups 639:644 Separate groups 630:644 Separate groups from each diet 630:659 Separate groups from each diet were supplemented with either α-, γ-, δ-tocotrienol or α-tocopherol (85 mg/kg/day) for the final 8 of the 16 weeks. 26446095 2 2 theme starch-rich 357:367 arg1 diet 373:376 a corn starch-rich (C) diet 350:376 a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides 350:425 METHODS Five groups of rats were fed a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides, while the other five groups were fed a diet (H) high in simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) and fats (beef tallow, total 24 %) for 16 weeks. 26446095 5 3 theme inflammatory 970:981 arg1 infiltration 988:999 inflammatory cell infiltration 970:999 inflammatory cell infiltration 970:999 α-Tocopherol, α-, γ- and δ-tocotrienols reduced collagen deposition and inflammatory cell infiltration in the heart. 26446095 9 4 theme adipose 1415:1421 arg1 tissue 1423:1428 adipose tissue 1415:1428 adipose tissue 1415:1428 Tocotrienols were measured in heart, liver and adipose tissue showing that chronic oral dosage delivered tocotrienols to these organs despite low or no detection of tocotrienols in plasma. 26446095 2 5 theme corn 352:355 arg1 diet 373:376 a corn starch-rich (C) diet 350:376 a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides 350:425 METHODS Five groups of rats were fed a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides, while the other five groups were fed a diet (H) high in simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) and fats (beef tallow, total 24 %) for 16 weeks. 26446095 2 6 from sucrose 519:525 arg1 food 530:533 food 530:533 food 530:533 METHODS Five groups of rats were fed a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides, while the other five groups were fed a diet (H) high in simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) and fats (beef tallow, total 24 %) for 16 weeks. 26446095 0 7 theme obese 109:113 arg1 rats 115:118 diet-induced obese rats 96:118 diet-induced obese rats 96:118 Anti-inflammatory γ- and δ-tocotrienols improve cardiovascular, liver and metabolic function in diet-induced obese rats. 26446095 2 8 theme % 539:539 arg1 fructose 541:548 25 % fructose 536:548 25 % fructose in drinking water 536:566 METHODS Five groups of rats were fed a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides, while the other five groups were fed a diet (H) high in simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) and fats (beef tallow, total 24 %) for 16 weeks. 26446095 2 8 theme % 539:539 arg1 fructose 506:513 fructose 506:513 fructose 506:513 METHODS Five groups of rats were fed a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides, while the other five groups were fed a diet (H) high in simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) and fats (beef tallow, total 24 %) for 16 weeks. 26446095 6 9 theme normalised 1079:1088 arg1 pressure 1105:1112 normalised systolic blood pressure 1079:1112 normalised systolic blood pressure 1079:1112 Only γ- and δ-tocotrienols improved cardiovascular function and normalised systolic blood pressure compared to H rats. 26446095 1 10 theme diet-induced 272:283 arg1 syndrome 295:302 diet-induced metabolic syndrome 272:302 diet-induced metabolic syndrome in rats 272:310 PURPOSE This study tested the hypothesis that γ- and δ-tocotrienols are more effective than α-tocotrienol and α-tocopherol in attenuating the signs of diet-induced metabolic syndrome in rats. 26446095 0 11 theme diet-induced 96:107 arg1 rats 115:118 diet-induced obese rats 96:118 diet-induced obese rats 96:118 Anti-inflammatory γ- and δ-tocotrienols improve cardiovascular, liver and metabolic function in diet-induced obese rats. 26446095 0 12 from liver 64:68 arg1 rats 115:118 diet-induced obese rats 96:118 diet-induced obese rats 96:118 Anti-inflammatory γ- and δ-tocotrienols improve cardiovascular, liver and metabolic function in diet-induced obese rats. 26446095 2 13 theme 25  536:538 arg1 % 539:539 % 539:539 % 539:539 METHODS Five groups of rats were fed a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides, while the other five groups were fed a diet (H) high in simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) and fats (beef tallow, total 24 %) for 16 weeks. 26446095 9 14 theme chronic 1443:1449 arg1 dosage 1456:1461 chronic oral dosage 1443:1461 chronic oral dosage delivered 1443:1471 Tocotrienols were measured in heart, liver and adipose tissue showing that chronic oral dosage delivered tocotrienols to these organs despite low or no detection of tocotrienols in plasma. 26446095 1 15 theme metabolic 285:293 arg1 syndrome 295:302 diet-induced metabolic syndrome 272:302 diet-induced metabolic syndrome in rats 272:310 PURPOSE This study tested the hypothesis that γ- and δ-tocotrienols are more effective than α-tocotrienol and α-tocopherol in attenuating the signs of diet-induced metabolic syndrome in rats. 26446095 2 16 theme high 476:479 arg1 H 473:473 H 473:473 H 473:473 METHODS Five groups of rats were fed a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides, while the other five groups were fed a diet (H) high in simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) and fats (beef tallow, total 24 %) for 16 weeks. 26446095 2 16 theme high 476:479 arg1 diet 467:470 a diet 465:470 a diet (H) high in simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) and fats (beef tallow, total 24 %) 465:614 METHODS Five groups of rats were fed a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides, while the other five groups were fed a diet (H) high in simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) and fats (beef tallow, total 24 %) for 16 weeks. 26446095 5 17 theme cell 983:986 arg1 infiltration 988:999 inflammatory cell infiltration 970:999 inflammatory cell infiltration 970:999 α-Tocopherol, α-, γ- and δ-tocotrienols reduced collagen deposition and inflammatory cell infiltration in the heart. 26446095 1 18 from rats 307:310 arg1 signs 263:267 the signs 259:267 the signs of diet-induced metabolic syndrome in rats 259:310 PURPOSE This study tested the hypothesis that γ- and δ-tocotrienols are more effective than α-tocotrienol and α-tocopherol in attenuating the signs of diet-induced metabolic syndrome in rats. 26446095 2 19 theme 68  575:577 arg1 fructose 506:513 fructose 506:513 fructose 506:513 METHODS Five groups of rats were fed a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides, while the other five groups were fed a diet (H) high in simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) and fats (beef tallow, total 24 %) for 16 weeks. 26446095 2 19 theme 68  575:577 arg1 % 578:578 total 68 % 569:578 total 68 % 569:578 METHODS Five groups of rats were fed a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides, while the other five groups were fed a diet (H) high in simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) and fats (beef tallow, total 24 %) for 16 weeks. 26446095 1 20 dep PURPOSE 121:127 arg1 tested 140:145 tested 140:145 tested the hypothesis that γ- and δ-tocotrienols are more effective than α-tocotrienol and α-tocopherol in attenuating the signs of diet-induced metabolic syndrome in rats 140:310 PURPOSE This study tested the hypothesis that γ- and δ-tocotrienols are more effective than α-tocotrienol and α-tocopherol in attenuating the signs of diet-induced metabolic syndrome in rats. 26446095 2 21 theme 68  389:391 arg1 % 392:392 % 392:392 % 392:392 METHODS Five groups of rats were fed a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides, while the other five groups were fed a diet (H) high in simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) and fats (beef tallow, total 24 %) for 16 weeks. 26446095 0 22 from cardiovascular 48:61 arg1 rats 115:118 diet-induced obese rats 96:118 diet-induced obese rats 96:118 Anti-inflammatory γ- and δ-tocotrienols improve cardiovascular, liver and metabolic function in diet-induced obese rats. 26446095 6 23 theme cardiovascular 1051:1064 arg1 function 1066:1073 cardiovascular function 1051:1073 cardiovascular function 1051:1073 Only γ- and δ-tocotrienols improved cardiovascular function and normalised systolic blood pressure compared to H rats. 26446095 4 24 theme visceral 802:809 arg1 obesity 811:817 visceral obesity 802:817 visceral obesity 802:817 RESULTS H rats developed visceral obesity, hypertension, insulin resistance, cardiovascular remodelling and fatty liver. 26446095 2 25 theme other 438:442 arg1 groups 449:454 the other five groups 434:454 the other five groups 434:454 METHODS Five groups of rats were fed a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides, while the other five groups were fed a diet (H) high in simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) and fats (beef tallow, total 24 %) for 16 weeks. 26446095 1 26 from syndrome 295:302 arg1 rats 307:310 rats 307:310 rats 307:310 PURPOSE This study tested the hypothesis that γ- and δ-tocotrienols are more effective than α-tocotrienol and α-tocopherol in attenuating the signs of diet-induced metabolic syndrome in rats. 26446095 2 27 theme beef 591:594 arg1 % 613:613 total 24 % 604:613 total 24 % 604:613 METHODS Five groups of rats were fed a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides, while the other five groups were fed a diet (H) high in simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) and fats (beef tallow, total 24 %) for 16 weeks. 26446095 2 27 theme beef 591:594 arg1 tallow 596:601 beef tallow 591:601 beef tallow 591:601 METHODS Five groups of rats were fed a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides, while the other five groups were fed a diet (H) high in simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) and fats (beef tallow, total 24 %) for 16 weeks. 26446095 10 28 theme modest 1712:1717 arg1 improvements 1719:1730 more modest improvements 1707:1730 more modest improvements 1707:1730 CONCLUSION In rats, δ-tocotrienol improved inflammation, heart structure and function, and liver structure and function, while γ-tocotrienol produced more modest improvements, with minimal changes with α-tocotrienol and α-tocopherol. 26446095 3 29 theme 16 weeks 767:774 arg1 8 758:758 8 758:758 8 758:758 Separate groups from each diet were supplemented with either α-, γ-, δ-tocotrienol or α-tocopherol (85 mg/kg/day) for the final 8 of the 16 weeks. 26446095 3 29 theme 16 weeks 767:774 arg1 16 weeks 767:774 the 16 weeks 763:774 the 16 weeks 763:774 Separate groups from each diet were supplemented with either α-, γ-, δ-tocotrienol or α-tocopherol (85 mg/kg/day) for the final 8 of the 16 weeks. 26446095 0 30 theme Anti-inflammatory 0:16 arg1 γ- 18:19 Anti-inflammatory γ- 0:19 Anti-inflammatory γ- 0:19 Anti-inflammatory γ- and δ-tocotrienols improve cardiovascular, liver and metabolic function in diet-induced obese rats. 26446095 1 31 theme syndrome 295:302 arg1 signs 263:267 the signs 259:267 the signs of diet-induced metabolic syndrome in rats 259:310 PURPOSE This study tested the hypothesis that γ- and δ-tocotrienols are more effective than α-tocotrienol and α-tocopherol in attenuating the signs of diet-induced metabolic syndrome in rats. 26446095 2 32 theme drinking 553:560 arg1 water 562:566 drinking water 553:566 drinking water 553:566 METHODS Five groups of rats were fed a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides, while the other five groups were fed a diet (H) high in simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) and fats (beef tallow, total 24 %) for 16 weeks. 26446095 10 33 theme heart 1614:1618 arg1 structure 1620:1628 heart structure 1614:1628 heart structure 1614:1628 CONCLUSION In rats, δ-tocotrienol improved inflammation, heart structure and function, and liver structure and function, while γ-tocotrienol produced more modest improvements, with minimal changes with α-tocotrienol and α-tocopherol. 26446095 2 34 theme total 569:573 arg1 fructose 506:513 fructose 506:513 fructose 506:513 METHODS Five groups of rats were fed a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides, while the other five groups were fed a diet (H) high in simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) and fats (beef tallow, total 24 %) for 16 weeks. 26446095 2 34 theme total 569:573 arg1 % 578:578 total 68 % 569:578 total 68 % 569:578 METHODS Five groups of rats were fed a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides, while the other five groups were fed a diet (H) high in simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) and fats (beef tallow, total 24 %) for 16 weeks. 26446095 9 35 from detection 1520:1528 arg1 plasma 1549:1554 plasma 1549:1554 plasma 1549:1554 Tocotrienols were measured in heart, liver and adipose tissue showing that chronic oral dosage delivered tocotrienols to these organs despite low or no detection of tocotrienols in plasma. 26446095 5 36 theme collagen 946:953 arg1 deposition 955:964 collagen deposition 946:964 collagen deposition 946:964 α-Tocopherol, α-, γ- and δ-tocotrienols reduced collagen deposition and inflammatory cell infiltration in the heart. 26446095 6 37 theme blood 1099:1103 arg1 pressure 1105:1112 normalised systolic blood pressure 1079:1112 normalised systolic blood pressure 1079:1112 Only γ- and δ-tocotrienols improved cardiovascular function and normalised systolic blood pressure compared to H rats. 26446095 10 38 theme liver 1648:1652 arg1 structure 1654:1662 liver structure 1648:1662 liver structure 1648:1662 CONCLUSION In rats, δ-tocotrienol improved inflammation, heart structure and function, and liver structure and function, while γ-tocotrienol produced more modest improvements, with minimal changes with α-tocotrienol and α-tocopherol. 26446095 8 39 theme lipid 1287:1291 arg1 accumulation 1293:1304 lipid accumulation 1287:1304 lipid accumulation 1287:1304 In the liver, these interventions reduced lipid accumulation, inflammatory infiltrates and plasma liver enzyme activities. 26446095 7 40 theme lipid 1206:1210 arg1 profile 1212:1218 lipid profile 1206:1218 lipid profile 1206:1218 Further, δ-tocotrienol improved glucose tolerance, insulin sensitivity, lipid profile and abdominal adiposity. 26446095 10 41 theme more 1707:1710 arg1 improvements 1719:1730 more modest improvements 1707:1730 more modest improvements 1707:1730 CONCLUSION In rats, δ-tocotrienol improved inflammation, heart structure and function, and liver structure and function, while γ-tocotrienol produced more modest improvements, with minimal changes with α-tocotrienol and α-tocopherol. 26446095 3 42 theme Separate 630:637 arg1 groups 639:644 Separate groups 630:644 Separate groups from each diet 630:659 Separate groups from each diet were supplemented with either α-, γ-, δ-tocotrienol or α-tocopherol (85 mg/kg/day) for the final 8 of the 16 weeks. 26446095 4 43 theme H 785:785 arg1 rats 787:790 H rats 785:790 H rats 785:790 RESULTS H rats developed visceral obesity, hypertension, insulin resistance, cardiovascular remodelling and fatty liver. 26446095 10 44 from CONCLUSION 1557:1566 arg1 rats 1571:1574 rats 1571:1574 rats 1571:1574 CONCLUSION In rats, δ-tocotrienol improved inflammation, heart structure and function, and liver structure and function, while γ-tocotrienol produced more modest improvements, with minimal changes with α-tocotrienol and α-tocopherol. 26446095 10 44 from CONCLUSION 1557:1566 arg1 δ-tocotrienol 1577:1589 δ-tocotrienol 1577:1589 δ-tocotrienol 1577:1589 CONCLUSION In rats, δ-tocotrienol improved inflammation, heart structure and function, and liver structure and function, while γ-tocotrienol produced more modest improvements, with minimal changes with α-tocotrienol and α-tocopherol. 26446095 9 45 theme oral 1451:1454 arg1 dosage 1456:1461 chronic oral dosage 1443:1461 chronic oral dosage delivered 1443:1471 Tocotrienols were measured in heart, liver and adipose tissue showing that chronic oral dosage delivered tocotrienols to these organs despite low or no detection of tocotrienols in plasma. 26446095 8 46 theme enzyme 1349:1354 arg1 activities 1356:1365 plasma liver enzyme activities 1336:1365 plasma liver enzyme activities 1336:1365 In the liver, these interventions reduced lipid accumulation, inflammatory infiltrates and plasma liver enzyme activities. 26446095 2 47 from fructose 541:548 arg1 water 562:566 drinking water 553:566 drinking water 553:566 METHODS Five groups of rats were fed a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides, while the other five groups were fed a diet (H) high in simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) and fats (beef tallow, total 24 %) for 16 weeks. 26446095 1 48 from signs 263:267 arg1 rats 307:310 rats 307:310 rats 307:310 PURPOSE This study tested the hypothesis that γ- and δ-tocotrienols are more effective than α-tocotrienol and α-tocopherol in attenuating the signs of diet-induced metabolic syndrome in rats. 26446095 0 49 from function 84:91 arg1 rats 115:118 diet-induced obese rats 96:118 diet-induced obese rats 96:118 Anti-inflammatory γ- and δ-tocotrienols improve cardiovascular, liver and metabolic function in diet-induced obese rats. 26446095 10 50 theme minimal 1738:1744 arg1 changes 1746:1752 minimal changes 1738:1752 minimal changes with α-tocotrienol and α-tocopherol 1738:1788 CONCLUSION In rats, δ-tocotrienol improved inflammation, heart structure and function, and liver structure and function, while γ-tocotrienol produced more modest improvements, with minimal changes with α-tocotrienol and α-tocopherol. 26446095 7 51 theme abdominal 1224:1232 arg1 adiposity 1234:1242 abdominal adiposity 1224:1242 abdominal adiposity 1224:1242 Further, δ-tocotrienol improved glucose tolerance, insulin sensitivity, lipid profile and abdominal adiposity. 26446095 11 52 theme important 1800:1808 arg1 mechanism 1810:1818 The most important mechanism 1791:1818 The most important mechanism of action 1791:1828 The most important mechanism of action is likely to be reduction in organ inflammation. 26446095 11 52 theme important 1800:1808 arg1 likely 1833:1838 likely 1833:1838 likely 1833:1838 The most important mechanism of action is likely to be reduction in organ inflammation. 26446095 11 52 theme important 1800:1808 arg1 reduction 1846:1854 reduction 1846:1854 reduction in organ inflammation 1846:1876 The most important mechanism of action is likely to be reduction in organ inflammation. 26446095 2 53 contain containing 378:387 arg2 polysaccharides 411:425 polysaccharides 411:425 polysaccharides 411:425 METHODS Five groups of rats were fed a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides, while the other five groups were fed a diet (H) high in simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) and fats (beef tallow, total 24 %) for 16 weeks. 26446095 2 53 contain containing 378:387 arg2 carbohydrates 394:406 68 % carbohydrates 389:406 68 % carbohydrates 389:406 METHODS Five groups of rats were fed a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides, while the other five groups were fed a diet (H) high in simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) and fats (beef tallow, total 24 %) for 16 weeks. 26446095 2 53 contain containing 378:387 arg1 diet 373:376 a corn starch-rich (C) diet 350:376 a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides 350:425 METHODS Five groups of rats were fed a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides, while the other five groups were fed a diet (H) high in simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) and fats (beef tallow, total 24 %) for 16 weeks. 26446095 11 54 from reduction 1846:1854 arg1 inflammation 1865:1876 organ inflammation 1859:1876 organ inflammation 1859:1876 The most important mechanism of action is likely to be reduction in organ inflammation. 26446095 2 55 theme % 392:392 arg1 carbohydrates 394:406 68 % carbohydrates 389:406 68 % carbohydrates 389:406 METHODS Five groups of rats were fed a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides, while the other five groups were fed a diet (H) high in simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) and fats (beef tallow, total 24 %) for 16 weeks. 26446095 2 55 theme % 392:392 arg1 polysaccharides 411:425 polysaccharides 411:425 polysaccharides 411:425 METHODS Five groups of rats were fed a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides, while the other five groups were fed a diet (H) high in simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) and fats (beef tallow, total 24 %) for 16 weeks. 26446095 2 56 theme simple 484:489 arg1 fructose 506:513 fructose 506:513 fructose 506:513 METHODS Five groups of rats were fed a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides, while the other five groups were fed a diet (H) high in simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) and fats (beef tallow, total 24 %) for 16 weeks. 26446095 2 56 theme simple 484:489 arg1 carbohydrates 491:503 simple carbohydrates 484:503 simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) 484:579 METHODS Five groups of rats were fed a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides, while the other five groups were fed a diet (H) high in simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) and fats (beef tallow, total 24 %) for 16 weeks. 26446095 2 56 theme simple 484:489 arg1 sucrose 519:525 sucrose 519:525 sucrose 519:525 METHODS Five groups of rats were fed a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides, while the other five groups were fed a diet (H) high in simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) and fats (beef tallow, total 24 %) for 16 weeks. 26446095 6 57 theme H 1126:1126 arg1 rats 1128:1131 H rats 1126:1131 H rats 1126:1131 Only γ- and δ-tocotrienols improved cardiovascular function and normalised systolic blood pressure compared to H rats. 26446095 2 58 theme 24  610:612 arg1 % 613:613 total 24 % 604:613 total 24 % 604:613 METHODS Five groups of rats were fed a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides, while the other five groups were fed a diet (H) high in simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) and fats (beef tallow, total 24 %) for 16 weeks. 26446095 2 58 theme 24  610:612 arg1 tallow 596:601 beef tallow 591:601 beef tallow 591:601 METHODS Five groups of rats were fed a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides, while the other five groups were fed a diet (H) high in simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) and fats (beef tallow, total 24 %) for 16 weeks. 26446095 4 59 theme fatty 885:889 arg1 liver 891:895 fatty liver 885:895 fatty liver 885:895 RESULTS H rats developed visceral obesity, hypertension, insulin resistance, cardiovascular remodelling and fatty liver. 26446095 11 60 theme action 1823:1828 arg1 mechanism 1810:1818 The most important mechanism 1791:1818 The most important mechanism of action 1791:1828 The most important mechanism of action is likely to be reduction in organ inflammation. 26446095 11 60 theme action 1823:1828 arg1 likely 1833:1838 likely 1833:1838 likely 1833:1838 The most important mechanism of action is likely to be reduction in organ inflammation. 26446095 11 60 theme action 1823:1828 arg1 reduction 1846:1854 reduction 1846:1854 reduction in organ inflammation 1846:1876 The most important mechanism of action is likely to be reduction in organ inflammation. 26446095 2 61 from high 476:479 arg1 fructose 506:513 fructose 506:513 fructose 506:513 METHODS Five groups of rats were fed a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides, while the other five groups were fed a diet (H) high in simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) and fats (beef tallow, total 24 %) for 16 weeks. 26446095 2 61 from high 476:479 arg1 carbohydrates 491:503 simple carbohydrates 484:503 simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) 484:579 METHODS Five groups of rats were fed a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides, while the other five groups were fed a diet (H) high in simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) and fats (beef tallow, total 24 %) for 16 weeks. 26446095 2 61 from high 476:479 arg1 sucrose 519:525 sucrose 519:525 sucrose 519:525 METHODS Five groups of rats were fed a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides, while the other five groups were fed a diet (H) high in simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) and fats (beef tallow, total 24 %) for 16 weeks. 26446095 2 61 from high 476:479 arg1 fats 585:588 fats 585:588 fats (beef tallow, total 24 %) 585:614 METHODS Five groups of rats were fed a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides, while the other five groups were fed a diet (H) high in simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) and fats (beef tallow, total 24 %) for 16 weeks. 26446095 8 62 theme inflammatory 1307:1318 arg1 infiltrates 1320:1330 inflammatory infiltrates 1307:1330 inflammatory infiltrates 1307:1330 In the liver, these interventions reduced lipid accumulation, inflammatory infiltrates and plasma liver enzyme activities. 26446095 2 63 theme total 604:608 arg1 % 613:613 total 24 % 604:613 total 24 % 604:613 METHODS Five groups of rats were fed a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides, while the other five groups were fed a diet (H) high in simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) and fats (beef tallow, total 24 %) for 16 weeks. 26446095 2 63 theme total 604:608 arg1 tallow 596:601 beef tallow 591:601 beef tallow 591:601 METHODS Five groups of rats were fed a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides, while the other five groups were fed a diet (H) high in simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) and fats (beef tallow, total 24 %) for 16 weeks. 26446095 2 64 dep METHODS 313:319 arg1 fed 346:348 fed 346:348 fed a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides 346:425 METHODS Five groups of rats were fed a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides, while the other five groups were fed a diet (H) high in simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) and fats (beef tallow, total 24 %) for 16 weeks. 26446095 8 65 theme liver 1343:1347 arg1 activities 1356:1365 plasma liver enzyme activities 1336:1365 plasma liver enzyme activities 1336:1365 In the liver, these interventions reduced lipid accumulation, inflammatory infiltrates and plasma liver enzyme activities. 26446095 9 66 theme tocotrienols 1533:1544 arg1 detection 1520:1528 low or no detection 1510:1528 low or no detection of tocotrienols in plasma 1510:1554 Tocotrienols were measured in heart, liver and adipose tissue showing that chronic oral dosage delivered tocotrienols to these organs despite low or no detection of tocotrienols in plasma. 26446095 8 67 theme plasma 1336:1341 arg1 activities 1356:1365 plasma liver enzyme activities 1336:1365 plasma liver enzyme activities 1336:1365 In the liver, these interventions reduced lipid accumulation, inflammatory infiltrates and plasma liver enzyme activities. 26446095 7 68 theme glucose 1166:1172 arg1 tolerance 1174:1182 glucose tolerance 1166:1182 glucose tolerance 1166:1182 Further, δ-tocotrienol improved glucose tolerance, insulin sensitivity, lipid profile and abdominal adiposity. 26446095 2 69 dep fats 585:588 arg1 % 613:613 total 24 % 604:613 total 24 % 604:613 METHODS Five groups of rats were fed a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides, while the other five groups were fed a diet (H) high in simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) and fats (beef tallow, total 24 %) for 16 weeks. 26446095 2 69 dep fats 585:588 arg1 tallow 596:601 beef tallow 591:601 beef tallow 591:601 METHODS Five groups of rats were fed a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides, while the other five groups were fed a diet (H) high in simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) and fats (beef tallow, total 24 %) for 16 weeks. 26446095 4 70 dep RESULTS 777:783 arg1 developed 792:800 developed 792:800 developed visceral obesity, hypertension, insulin resistance, cardiovascular remodelling and fatty liver 792:895 RESULTS H rats developed visceral obesity, hypertension, insulin resistance, cardiovascular remodelling and fatty liver. 26446095 7 71 theme insulin 1185:1191 arg1 sensitivity 1193:1203 insulin sensitivity 1185:1203 insulin sensitivity 1185:1203 Further, δ-tocotrienol improved glucose tolerance, insulin sensitivity, lipid profile and abdominal adiposity. 26446095 10 72 with changes 1746:1752 arg1 α-tocopherol 1777:1788 α-tocopherol 1777:1788 α-tocopherol 1777:1788 CONCLUSION In rats, δ-tocotrienol improved inflammation, heart structure and function, and liver structure and function, while γ-tocotrienol produced more modest improvements, with minimal changes with α-tocotrienol and α-tocopherol. 26446095 10 72 with changes 1746:1752 arg1 α-tocotrienol 1759:1771 α-tocotrienol 1759:1771 α-tocotrienol 1759:1771 CONCLUSION In rats, δ-tocotrienol improved inflammation, heart structure and function, and liver structure and function, while γ-tocotrienol produced more modest improvements, with minimal changes with α-tocotrienol and α-tocopherol. 26446095 2 73 theme rats 336:339 arg1 rats 336:339 rats 336:339 rats 336:339 METHODS Five groups of rats were fed a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides, while the other five groups were fed a diet (H) high in simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) and fats (beef tallow, total 24 %) for 16 weeks. 26446095 2 73 theme rats 336:339 arg1 groups 326:331 Five groups 321:331 Five groups of rats 321:339 METHODS Five groups of rats were fed a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides, while the other five groups were fed a diet (H) high in simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) and fats (beef tallow, total 24 %) for 16 weeks. 26446095 2 74 from carbohydrates 491:503 arg1 high 476:479 high 476:479 high 476:479 METHODS Five groups of rats were fed a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides, while the other five groups were fed a diet (H) high in simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) and fats (beef tallow, total 24 %) for 16 weeks. 26446095 0 75 theme metabolic 74:82 arg1 function 84:91 metabolic function 74:91 metabolic function 74:91 Anti-inflammatory γ- and δ-tocotrienols improve cardiovascular, liver and metabolic function in diet-induced obese rats. 26446095 2 76 dep carbohydrates 491:503 arg1 fructose 506:513 fructose 506:513 fructose 506:513 METHODS Five groups of rats were fed a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides, while the other five groups were fed a diet (H) high in simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) and fats (beef tallow, total 24 %) for 16 weeks. 26446095 2 76 dep carbohydrates 491:503 arg1 fructose 541:548 25 % fructose 536:548 25 % fructose in drinking water 536:566 METHODS Five groups of rats were fed a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides, while the other five groups were fed a diet (H) high in simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) and fats (beef tallow, total 24 %) for 16 weeks. 26446095 2 76 dep carbohydrates 491:503 arg1 carbohydrates 491:503 simple carbohydrates 484:503 simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) 484:579 METHODS Five groups of rats were fed a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides, while the other five groups were fed a diet (H) high in simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) and fats (beef tallow, total 24 %) for 16 weeks. 26446095 2 76 dep carbohydrates 491:503 arg1 % 578:578 total 68 % 569:578 total 68 % 569:578 METHODS Five groups of rats were fed a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides, while the other five groups were fed a diet (H) high in simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) and fats (beef tallow, total 24 %) for 16 weeks. 26446095 2 76 dep carbohydrates 491:503 arg1 sucrose 519:525 sucrose 519:525 sucrose 519:525 METHODS Five groups of rats were fed a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides, while the other five groups were fed a diet (H) high in simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) and fats (beef tallow, total 24 %) for 16 weeks. 26446095 11 77 theme organ 1859:1863 arg1 inflammation 1865:1876 organ inflammation 1859:1876 organ inflammation 1859:1876 The most important mechanism of action is likely to be reduction in organ inflammation. 26446095 2 78 theme C 370:370 arg1 diet 373:376 a corn starch-rich (C) diet 350:376 a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides 350:425 METHODS Five groups of rats were fed a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides, while the other five groups were fed a diet (H) high in simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) and fats (beef tallow, total 24 %) for 16 weeks. 26446095 4 79 theme insulin 834:840 arg1 resistance 842:851 insulin resistance 834:851 insulin resistance 834:851 RESULTS H rats developed visceral obesity, hypertension, insulin resistance, cardiovascular remodelling and fatty liver. 26446095 6 80 theme systolic 1090:1097 arg1 pressure 1105:1112 normalised systolic blood pressure 1079:1112 normalised systolic blood pressure 1079:1112 Only γ- and δ-tocotrienols improved cardiovascular function and normalised systolic blood pressure compared to H rats. 26446095 2 81 from fats 585:588 arg1 high 476:479 high 476:479 high 476:479 METHODS Five groups of rats were fed a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides, while the other five groups were fed a diet (H) high in simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) and fats (beef tallow, total 24 %) for 16 weeks. 26446095 2 82 from fructose 506:513 arg1 food 530:533 food 530:533 food 530:533 METHODS Five groups of rats were fed a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides, while the other five groups were fed a diet (H) high in simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) and fats (beef tallow, total 24 %) for 16 weeks. 26295400 6 0 dep A. 928:929 arg1 equina 931:936 equina 931:936 equina 931:936 The A. equina mucus is mainly composed by water (96.2% ± 0.3%), whereas its dry weight is made of 24.2% ± 1.3% proteins and 7.8% ± 0.2% carbohydrates, with the smallest and largest components referable to lipids (0.9%) and inorganic matter (67.1%). 26295400 8 1 theme compounds 1630:1638 arg1 source 1610:1615 a source 1608:1615 a source of bioactive compounds of high pharmaceutical and biotechnological interest 1608:1691 The findings from this study improve the available information on the mucus composition in invertebrates and have implications for future investigations related to exploitation of A. equina and other sea anemones' mucus as a source of bioactive compounds of high pharmaceutical and biotechnological interest. 26295400 8 1 theme compounds 1630:1638 arg1 implications 1499:1510 implications 1499:1510 implications for future investigations related to exploitation of A. equina and other sea anemones' mucus 1499:1603 The findings from this study improve the available information on the mucus composition in invertebrates and have implications for future investigations related to exploitation of A. equina and other sea anemones' mucus as a source of bioactive compounds of high pharmaceutical and biotechnological interest. 26295400 7 2 theme tumor 1284:1288 arg1 K562 1300:1303 the tumor cell line K562 1280:1303 the tumor cell line K562 (human erythromyeloblastoid leukemia) 1280:1341 The A. equina mucus matrix exhibited hemolytic activity on rabbit erythrocytes, cytotoxic activity against the tumor cell line K562 (human erythromyeloblastoid leukemia) and antibacterial lysozyme-like activity. 26295400 7 2 theme tumor 1284:1288 arg1 leukemia 1333:1340 human erythromyeloblastoid leukemia 1306:1340 human erythromyeloblastoid leukemia 1306:1340 The A. equina mucus matrix exhibited hemolytic activity on rabbit erythrocytes, cytotoxic activity against the tumor cell line K562 (human erythromyeloblastoid leukemia) and antibacterial lysozyme-like activity. 26295400 1 3 theme weak 216:219 arg1 gel 228:230 a weak watery gel 214:230 a weak watery gel 214:230 The mucus produced by many marine organisms is a complex mixture of proteins and polysaccharides forming a weak watery gel. 26295400 6 4 theme ± 979:979 arg1 % 984:984 96.2% ± 0.3% 973:984 96.2% ± 0.3% 973:984 The A. equina mucus is mainly composed by water (96.2% ± 0.3%), whereas its dry weight is made of 24.2% ± 1.3% proteins and 7.8% ± 0.2% carbohydrates, with the smallest and largest components referable to lipids (0.9%) and inorganic matter (67.1%). 26295400 6 4 theme ± 979:979 arg1 water 966:970 water 966:970 water (96.2% ± 0.3%) 966:985 The A. equina mucus is mainly composed by water (96.2% ± 0.3%), whereas its dry weight is made of 24.2% ± 1.3% proteins and 7.8% ± 0.2% carbohydrates, with the smallest and largest components referable to lipids (0.9%) and inorganic matter (67.1%). 26295400 7 5 theme line 1295:1298 arg1 K562 1300:1303 the tumor cell line K562 1280:1303 the tumor cell line K562 (human erythromyeloblastoid leukemia) 1280:1341 The A. equina mucus matrix exhibited hemolytic activity on rabbit erythrocytes, cytotoxic activity against the tumor cell line K562 (human erythromyeloblastoid leukemia) and antibacterial lysozyme-like activity. 26295400 7 5 theme line 1295:1298 arg1 leukemia 1333:1340 human erythromyeloblastoid leukemia 1306:1340 human erythromyeloblastoid leukemia 1306:1340 The A. equina mucus matrix exhibited hemolytic activity on rabbit erythrocytes, cytotoxic activity against the tumor cell line K562 (human erythromyeloblastoid leukemia) and antibacterial lysozyme-like activity. 26295400 6 6 theme largest 1097:1103 arg1 components 1105:1114 the smallest and largest components 1080:1114 components 1105:1114 The A. equina mucus is mainly composed by water (96.2% ± 0.3%), whereas its dry weight is made of 24.2% ± 1.3% proteins and 7.8% ± 0.2% carbohydrates, with the smallest and largest components referable to lipids (0.9%) and inorganic matter (67.1%). 26295400 8 7 theme pharmaceutical 1648:1661 arg1 compounds 1630:1638 bioactive compounds 1620:1638 bioactive compounds of high pharmaceutical and biotechnological interest 1620:1691 The findings from this study improve the available information on the mucus composition in invertebrates and have implications for future investigations related to exploitation of A. equina and other sea anemones' mucus as a source of bioactive compounds of high pharmaceutical and biotechnological interest. 26295400 1 8 theme many 131:134 arg1 organisms 143:151 many marine organisms 131:151 many marine organisms 131:151 The mucus produced by many marine organisms is a complex mixture of proteins and polysaccharides forming a weak watery gel. 26295400 1 9 theme watery 221:226 arg1 gel 228:230 a weak watery gel 214:230 a weak watery gel 214:230 The mucus produced by many marine organisms is a complex mixture of proteins and polysaccharides forming a weak watery gel. 26295400 7 10 theme A. 1177:1178 arg1 matrix 1193:1198 The A. equina mucus matrix 1173:1198 The A. equina mucus matrix 1173:1198 The A. equina mucus matrix exhibited hemolytic activity on rabbit erythrocytes, cytotoxic activity against the tumor cell line K562 (human erythromyeloblastoid leukemia) and antibacterial lysozyme-like activity. 26295400 6 11 theme % 1051:1051 arg1 % 1058:1058 7.8% ± 0.2% 1048:1058 7.8% ± 0.2% carbohydrates 1048:1072 The A. equina mucus is mainly composed by water (96.2% ± 0.3%), whereas its dry weight is made of 24.2% ± 1.3% proteins and 7.8% ± 0.2% carbohydrates, with the smallest and largest components referable to lipids (0.9%) and inorganic matter (67.1%). 26295400 6 12 theme % 1026:1026 arg1 % 1033:1033 24.2% ± 1.3% 1022:1033 24.2% ± 1.3% proteins 1022:1042 The A. equina mucus is mainly composed by water (96.2% ± 0.3%), whereas its dry weight is made of 24.2% ± 1.3% proteins and 7.8% ± 0.2% carbohydrates, with the smallest and largest components referable to lipids (0.9%) and inorganic matter (67.1%). 26295400 7 13 dep A. 1177:1178 arg1 equina 1180:1185 equina 1180:1185 equina 1180:1185 The A. equina mucus matrix exhibited hemolytic activity on rabbit erythrocytes, cytotoxic activity against the tumor cell line K562 (human erythromyeloblastoid leukemia) and antibacterial lysozyme-like activity. 26295400 0 14 theme Unexplored 53:62 arg1 Resource 64:71 An Unexplored Resource 50:71 The Mucus of Actinia equina (Anthozoa, Cnidaria): An Unexplored Resource for Potential Applicative Purposes. 0:107 The Mucus of Actinia equina (Anthozoa, Cnidaria): An Unexplored Resource for Potential Applicative Purposes. 26295400 6 15 dep composed 954:961 arg1 whereas 988:994 whereas 988:994 whereas 988:994 The A. equina mucus is mainly composed by water (96.2% ± 0.3%), whereas its dry weight is made of 24.2% ± 1.3% proteins and 7.8% ± 0.2% carbohydrates, with the smallest and largest components referable to lipids (0.9%) and inorganic matter (67.1%). 26295400 8 16 theme biotechnological 1667:1682 arg1 interest 1684:1691 high pharmaceutical and biotechnological interest 1643:1691 interest 1684:1691 The findings from this study improve the available information on the mucus composition in invertebrates and have implications for future investigations related to exploitation of A. equina and other sea anemones' mucus as a source of bioactive compounds of high pharmaceutical and biotechnological interest. 26295400 3 17 theme benthic 496:502 arg1 anemone 523:529 the sea anemone 515:529 the sea anemone Actinia equina (Linnaeus, 1758) for preventing burial by excess sedimentation and for protection 515:626 In the present study we focused on mucus produced by a benthic cnidarian, the sea anemone Actinia equina (Linnaeus, 1758) for preventing burial by excess sedimentation and for protection. 26295400 3 17 theme benthic 496:502 arg1 cnidarian 504:512 a benthic cnidarian 494:512 a benthic cnidarian 494:512 In the present study we focused on mucus produced by a benthic cnidarian, the sea anemone Actinia equina (Linnaeus, 1758) for preventing burial by excess sedimentation and for protection. 26295400 6 18 theme A. 928:929 arg1 mucus 938:942 The A. equina mucus 924:942 The A. equina mucus 924:942 The A. equina mucus is mainly composed by water (96.2% ± 0.3%), whereas its dry weight is made of 24.2% ± 1.3% proteins and 7.8% ± 0.2% carbohydrates, with the smallest and largest components referable to lipids (0.9%) and inorganic matter (67.1%). 26295400 0 19 theme Potential 77:85 arg1 Purposes 99:106 Potential Applicative Purposes 77:106 Potential Applicative Purposes 77:106 The Mucus of Actinia equina (Anthozoa, Cnidaria): An Unexplored Resource for Potential Applicative Purposes. 26295400 3 20 theme present 448:454 arg1 study 456:460 the present study 444:460 the present study 444:460 In the present study we focused on mucus produced by a benthic cnidarian, the sea anemone Actinia equina (Linnaeus, 1758) for preventing burial by excess sedimentation and for protection. 26295400 6 21 theme referable 1116:1124 arg1 components 1105:1114 the smallest and largest components 1080:1114 components 1105:1114 The A. equina mucus is mainly composed by water (96.2% ± 0.3%), whereas its dry weight is made of 24.2% ± 1.3% proteins and 7.8% ± 0.2% carbohydrates, with the smallest and largest components referable to lipids (0.9%) and inorganic matter (67.1%). 26295400 6 22 theme % 977:977 arg1 % 984:984 96.2% ± 0.3% 973:984 96.2% ± 0.3% 973:984 The A. equina mucus is mainly composed by water (96.2% ± 0.3%), whereas its dry weight is made of 24.2% ± 1.3% proteins and 7.8% ± 0.2% carbohydrates, with the smallest and largest components referable to lipids (0.9%) and inorganic matter (67.1%). 26295400 6 22 theme % 977:977 arg1 water 966:970 water 966:970 water (96.2% ± 0.3%) 966:985 The A. equina mucus is mainly composed by water (96.2% ± 0.3%), whereas its dry weight is made of 24.2% ± 1.3% proteins and 7.8% ± 0.2% carbohydrates, with the smallest and largest components referable to lipids (0.9%) and inorganic matter (67.1%). 26295400 8 23 theme bioactive 1620:1628 arg1 compounds 1630:1638 bioactive compounds 1620:1638 bioactive compounds of high pharmaceutical and biotechnological interest 1620:1691 The findings from this study improve the available information on the mucus composition in invertebrates and have implications for future investigations related to exploitation of A. equina and other sea anemones' mucus as a source of bioactive compounds of high pharmaceutical and biotechnological interest. 26295400 1 24 theme marine 136:141 arg1 organisms 143:151 many marine organisms 131:151 many marine organisms 131:151 The mucus produced by many marine organisms is a complex mixture of proteins and polysaccharides forming a weak watery gel. 26295400 3 25 dep Linnaeus 547:554 arg1 1758 557:560 1758 557:560 1758 557:560 In the present study we focused on mucus produced by a benthic cnidarian, the sea anemone Actinia equina (Linnaeus, 1758) for preventing burial by excess sedimentation and for protection. 26295400 8 26 from study 1408:1412 arg1 findings 1389:1396 The findings 1385:1396 The findings from this study 1385:1412 The findings from this study improve the available information on the mucus composition in invertebrates and have implications for future investigations related to exploitation of A. equina and other sea anemones' mucus as a source of bioactive compounds of high pharmaceutical and biotechnological interest. 26295400 3 27 dep Actinia 531:537 arg1 equina 539:544 equina 539:544 equina 539:544 In the present study we focused on mucus produced by a benthic cnidarian, the sea anemone Actinia equina (Linnaeus, 1758) for preventing burial by excess sedimentation and for protection. 26295400 3 27 dep Actinia 531:537 arg1 Linnaeus 547:554 Linnaeus 547:554 Linnaeus 547:554 In the present study we focused on mucus produced by a benthic cnidarian, the sea anemone Actinia equina (Linnaeus, 1758) for preventing burial by excess sedimentation and for protection. 26295400 2 28 theme parasites 415:423 arg1 multitude 367:375 a multitude 365:375 a multitude of environmental stresses, predators, parasites, and pathogens 365:438 It is essential for vital processes including locomotion, navigation, structural support, heterotrophic feeding and defence against a multitude of environmental stresses, predators, parasites, and pathogens. 26295400 6 29 theme % 1033:1033 arg1 proteins 1035:1042 24.2% ± 1.3% proteins 1022:1042 24.2% ± 1.3% proteins 1022:1042 The A. equina mucus is mainly composed by water (96.2% ± 0.3%), whereas its dry weight is made of 24.2% ± 1.3% proteins and 7.8% ± 0.2% carbohydrates, with the smallest and largest components referable to lipids (0.9%) and inorganic matter (67.1%). 26295400 4 30 theme lipid 789:793 arg1 contents 795:802 total lipid contents 783:802 total lipid contents 783:802 We investigated some of the physico-chemical properties of this matrix such as viscosity, osmolarity, electrical conductivity, protein, carbohydrate, and total lipid contents. 26295400 8 31 theme interest 1684:1691 arg1 compounds 1630:1638 bioactive compounds 1620:1638 bioactive compounds of high pharmaceutical and biotechnological interest 1620:1691 The findings from this study improve the available information on the mucus composition in invertebrates and have implications for future investigations related to exploitation of A. equina and other sea anemones' mucus as a source of bioactive compounds of high pharmaceutical and biotechnological interest. 26295400 5 32 theme antibacterial 866:878 arg1 activities 894:903 antibacterial lysozyme-like activities 866:903 antibacterial lysozyme-like activities 866:903 Some biological activities such as hemolytic, cytotoxic, and antibacterial lysozyme-like activities were also studied. 26295400 7 33 theme cell 1290:1293 arg1 K562 1300:1303 the tumor cell line K562 1280:1303 the tumor cell line K562 (human erythromyeloblastoid leukemia) 1280:1341 The A. equina mucus matrix exhibited hemolytic activity on rabbit erythrocytes, cytotoxic activity against the tumor cell line K562 (human erythromyeloblastoid leukemia) and antibacterial lysozyme-like activity. 26295400 7 33 theme cell 1290:1293 arg1 leukemia 1333:1340 human erythromyeloblastoid leukemia 1306:1340 human erythromyeloblastoid leukemia 1306:1340 The A. equina mucus matrix exhibited hemolytic activity on rabbit erythrocytes, cytotoxic activity against the tumor cell line K562 (human erythromyeloblastoid leukemia) and antibacterial lysozyme-like activity. 26295400 7 34 theme cytotoxic 1253:1261 arg1 activity 1263:1270 cytotoxic activity 1253:1270 cytotoxic activity against the tumor cell line K562 (human erythromyeloblastoid leukemia) 1253:1341 The A. equina mucus matrix exhibited hemolytic activity on rabbit erythrocytes, cytotoxic activity against the tumor cell line K562 (human erythromyeloblastoid leukemia) and antibacterial lysozyme-like activity. 26295400 4 35 theme total 783:787 arg1 contents 795:802 total lipid contents 783:802 total lipid contents 783:802 We investigated some of the physico-chemical properties of this matrix such as viscosity, osmolarity, electrical conductivity, protein, carbohydrate, and total lipid contents. 26295400 7 36 theme human 1306:1310 arg1 K562 1300:1303 the tumor cell line K562 1280:1303 the tumor cell line K562 (human erythromyeloblastoid leukemia) 1280:1341 The A. equina mucus matrix exhibited hemolytic activity on rabbit erythrocytes, cytotoxic activity against the tumor cell line K562 (human erythromyeloblastoid leukemia) and antibacterial lysozyme-like activity. 26295400 7 36 theme human 1306:1310 arg1 leukemia 1333:1340 human erythromyeloblastoid leukemia 1306:1340 human erythromyeloblastoid leukemia 1306:1340 The A. equina mucus matrix exhibited hemolytic activity on rabbit erythrocytes, cytotoxic activity against the tumor cell line K562 (human erythromyeloblastoid leukemia) and antibacterial lysozyme-like activity. 26295400 3 37 theme sea 519:521 arg1 anemone 523:529 the sea anemone 515:529 the sea anemone Actinia equina (Linnaeus, 1758) for preventing burial by excess sedimentation and for protection 515:626 In the present study we focused on mucus produced by a benthic cnidarian, the sea anemone Actinia equina (Linnaeus, 1758) for preventing burial by excess sedimentation and for protection. 26295400 3 37 theme sea 519:521 arg1 cnidarian 504:512 a benthic cnidarian 494:512 a benthic cnidarian 494:512 In the present study we focused on mucus produced by a benthic cnidarian, the sea anemone Actinia equina (Linnaeus, 1758) for preventing burial by excess sedimentation and for protection. 26295400 8 38 theme sea 1585:1587 arg1 anemones 1589:1596 other sea anemones 1579:1596 other sea anemones 1579:1596 The findings from this study improve the available information on the mucus composition in invertebrates and have implications for future investigations related to exploitation of A. equina and other sea anemones' mucus as a source of bioactive compounds of high pharmaceutical and biotechnological interest. 26295400 5 39 theme biological 810:819 arg1 activities 894:903 antibacterial lysozyme-like activities 866:903 antibacterial lysozyme-like activities 866:903 Some biological activities such as hemolytic, cytotoxic, and antibacterial lysozyme-like activities were also studied. 26295400 5 39 theme biological 810:819 arg1 cytotoxic 851:859 cytotoxic 851:859 cytotoxic 851:859 Some biological activities such as hemolytic, cytotoxic, and antibacterial lysozyme-like activities were also studied. 26295400 5 39 theme biological 810:819 arg1 activities 821:830 Some biological activities 805:830 Some biological activities such as hemolytic, cytotoxic, and antibacterial lysozyme-like activities 805:903 Some biological activities such as hemolytic, cytotoxic, and antibacterial lysozyme-like activities were also studied. 26295400 5 39 theme biological 810:819 arg1 hemolytic 840:848 hemolytic 840:848 hemolytic 840:848 Some biological activities such as hemolytic, cytotoxic, and antibacterial lysozyme-like activities were also studied. 26295400 0 40 theme Actinia 13:19 arg1 equina 21:26 Actinia equina 13:26 Actinia equina 13:26 The Mucus of Actinia equina (Anthozoa, Cnidaria): An Unexplored Resource for Potential Applicative Purposes. 26295400 7 41 theme rabbit 1232:1237 arg1 erythrocytes 1239:1250 rabbit erythrocytes 1232:1250 rabbit erythrocytes 1232:1250 The A. equina mucus matrix exhibited hemolytic activity on rabbit erythrocytes, cytotoxic activity against the tumor cell line K562 (human erythromyeloblastoid leukemia) and antibacterial lysozyme-like activity. 26295400 7 42 theme mucus 1187:1191 arg1 matrix 1193:1198 The A. equina mucus matrix 1173:1198 The A. equina mucus matrix 1173:1198 The A. equina mucus matrix exhibited hemolytic activity on rabbit erythrocytes, cytotoxic activity against the tumor cell line K562 (human erythromyeloblastoid leukemia) and antibacterial lysozyme-like activity. 26295400 4 43 theme matrix 693:698 arg1 conductivity 742:753 electrical conductivity 731:753 electrical conductivity 731:753 We investigated some of the physico-chemical properties of this matrix such as viscosity, osmolarity, electrical conductivity, protein, carbohydrate, and total lipid contents. 26295400 4 43 theme matrix 693:698 arg1 viscosity 708:716 viscosity 708:716 viscosity 708:716 We investigated some of the physico-chemical properties of this matrix such as viscosity, osmolarity, electrical conductivity, protein, carbohydrate, and total lipid contents. 26295400 4 43 theme matrix 693:698 arg1 protein 756:762 protein 756:762 protein 756:762 We investigated some of the physico-chemical properties of this matrix such as viscosity, osmolarity, electrical conductivity, protein, carbohydrate, and total lipid contents. 26295400 4 43 theme matrix 693:698 arg1 properties 674:683 the physico-chemical properties 653:683 the physico-chemical properties of this matrix such as viscosity, osmolarity, electrical conductivity, protein, carbohydrate, and total lipid contents 653:802 We investigated some of the physico-chemical properties of this matrix such as viscosity, osmolarity, electrical conductivity, protein, carbohydrate, and total lipid contents. 26295400 4 43 theme matrix 693:698 arg1 contents 795:802 total lipid contents 783:802 total lipid contents 783:802 We investigated some of the physico-chemical properties of this matrix such as viscosity, osmolarity, electrical conductivity, protein, carbohydrate, and total lipid contents. 26295400 4 43 theme matrix 693:698 arg1 carbohydrate 765:776 carbohydrate 765:776 carbohydrate 765:776 We investigated some of the physico-chemical properties of this matrix such as viscosity, osmolarity, electrical conductivity, protein, carbohydrate, and total lipid contents. 26295400 4 43 theme matrix 693:698 arg1 osmolarity 719:728 osmolarity 719:728 osmolarity 719:728 We investigated some of the physico-chemical properties of this matrix such as viscosity, osmolarity, electrical conductivity, protein, carbohydrate, and total lipid contents. 26295400 8 44 theme other 1579:1583 arg1 anemones 1589:1596 other sea anemones 1579:1596 other sea anemones 1579:1596 The findings from this study improve the available information on the mucus composition in invertebrates and have implications for future investigations related to exploitation of A. equina and other sea anemones' mucus as a source of bioactive compounds of high pharmaceutical and biotechnological interest. 26295400 2 45 theme stresses 394:401 arg1 multitude 367:375 a multitude 365:375 a multitude of environmental stresses, predators, parasites, and pathogens 365:438 It is essential for vital processes including locomotion, navigation, structural support, heterotrophic feeding and defence against a multitude of environmental stresses, predators, parasites, and pathogens. 26295400 5 46 theme lysozyme-like 880:892 arg1 activities 894:903 antibacterial lysozyme-like activities 866:903 antibacterial lysozyme-like activities 866:903 Some biological activities such as hemolytic, cytotoxic, and antibacterial lysozyme-like activities were also studied. 26295400 0 47 theme Applicative 87:97 arg1 Purposes 99:106 Potential Applicative Purposes 77:106 Potential Applicative Purposes 77:106 The Mucus of Actinia equina (Anthozoa, Cnidaria): An Unexplored Resource for Potential Applicative Purposes. 26295400 2 48 theme vital 253:257 arg1 processes 259:267 vital processes 253:267 vital processes including locomotion, navigation, structural support, heterotrophic feeding and defence against a multitude of environmental stresses, predators, parasites, and pathogens 253:438 It is essential for vital processes including locomotion, navigation, structural support, heterotrophic feeding and defence against a multitude of environmental stresses, predators, parasites, and pathogens. 26295400 2 48 theme vital 253:257 arg1 support 314:320 structural support 303:320 structural support 303:320 It is essential for vital processes including locomotion, navigation, structural support, heterotrophic feeding and defence against a multitude of environmental stresses, predators, parasites, and pathogens. 26295400 2 48 theme vital 253:257 arg1 locomotion 279:288 locomotion 279:288 locomotion 279:288 It is essential for vital processes including locomotion, navigation, structural support, heterotrophic feeding and defence against a multitude of environmental stresses, predators, parasites, and pathogens. 26295400 2 48 theme vital 253:257 arg1 feeding 337:343 heterotrophic feeding 323:343 heterotrophic feeding 323:343 It is essential for vital processes including locomotion, navigation, structural support, heterotrophic feeding and defence against a multitude of environmental stresses, predators, parasites, and pathogens. 26295400 2 48 theme vital 253:257 arg1 navigation 291:300 navigation 291:300 navigation 291:300 It is essential for vital processes including locomotion, navigation, structural support, heterotrophic feeding and defence against a multitude of environmental stresses, predators, parasites, and pathogens. 26295400 2 48 theme vital 253:257 arg1 defence 349:355 defence 349:355 defence against a multitude of environmental stresses, predators, parasites, and pathogens 349:438 It is essential for vital processes including locomotion, navigation, structural support, heterotrophic feeding and defence against a multitude of environmental stresses, predators, parasites, and pathogens. 26295400 8 49 contain have 1494:1497 arg2 source 1610:1615 a source 1608:1615 a source of bioactive compounds of high pharmaceutical and biotechnological interest 1608:1691 The findings from this study improve the available information on the mucus composition in invertebrates and have implications for future investigations related to exploitation of A. equina and other sea anemones' mucus as a source of bioactive compounds of high pharmaceutical and biotechnological interest. 26295400 8 49 contain have 1494:1497 arg1 findings 1389:1396 The findings 1385:1396 The findings from this study 1385:1412 The findings from this study improve the available information on the mucus composition in invertebrates and have implications for future investigations related to exploitation of A. equina and other sea anemones' mucus as a source of bioactive compounds of high pharmaceutical and biotechnological interest. 26295400 8 49 contain have 1494:1497 arg2 implications 1499:1510 implications 1499:1510 implications for future investigations related to exploitation of A. equina and other sea anemones' mucus 1499:1603 The findings from this study improve the available information on the mucus composition in invertebrates and have implications for future investigations related to exploitation of A. equina and other sea anemones' mucus as a source of bioactive compounds of high pharmaceutical and biotechnological interest. 26295400 2 50 theme environmental 380:392 arg1 stresses 394:401 environmental stresses 380:401 environmental stresses 380:401 It is essential for vital processes including locomotion, navigation, structural support, heterotrophic feeding and defence against a multitude of environmental stresses, predators, parasites, and pathogens. 26295400 6 51 theme smallest 1084:1091 arg1 components 1105:1114 the smallest and largest components 1080:1114 components 1105:1114 The A. equina mucus is mainly composed by water (96.2% ± 0.3%), whereas its dry weight is made of 24.2% ± 1.3% proteins and 7.8% ± 0.2% carbohydrates, with the smallest and largest components referable to lipids (0.9%) and inorganic matter (67.1%). 26295400 7 52 theme hemolytic 1210:1218 arg1 activity 1220:1227 hemolytic activity 1210:1227 hemolytic activity on rabbit erythrocytes 1210:1250 The A. equina mucus matrix exhibited hemolytic activity on rabbit erythrocytes, cytotoxic activity against the tumor cell line K562 (human erythromyeloblastoid leukemia) and antibacterial lysozyme-like activity. 26295400 2 53 theme pathogens 430:438 arg1 multitude 367:375 a multitude 365:375 a multitude of environmental stresses, predators, parasites, and pathogens 365:438 It is essential for vital processes including locomotion, navigation, structural support, heterotrophic feeding and defence against a multitude of environmental stresses, predators, parasites, and pathogens. 26295400 0 54 theme equina 21:26 arg1 Mucus 4:8 The Mucus 0:8 The Mucus of Actinia equina (Anthozoa, Cnidaria): An Unexplored Resource for Potential Applicative Purposes. 0:107 The Mucus of Actinia equina (Anthozoa, Cnidaria): An Unexplored Resource for Potential Applicative Purposes. 26295400 7 55 theme antibacterial 1347:1359 arg1 activity 1375:1382 antibacterial lysozyme-like activity 1347:1382 antibacterial lysozyme-like activity 1347:1382 The A. equina mucus matrix exhibited hemolytic activity on rabbit erythrocytes, cytotoxic activity against the tumor cell line K562 (human erythromyeloblastoid leukemia) and antibacterial lysozyme-like activity. 26295400 2 56 theme predators 404:412 arg1 multitude 367:375 a multitude 365:375 a multitude of environmental stresses, predators, parasites, and pathogens 365:438 It is essential for vital processes including locomotion, navigation, structural support, heterotrophic feeding and defence against a multitude of environmental stresses, predators, parasites, and pathogens. 26295400 1 57 theme proteins 177:184 arg1 mixture 166:172 a complex mixture 156:172 a complex mixture of proteins and polysaccharides forming a weak watery gel 156:230 The mucus produced by many marine organisms is a complex mixture of proteins and polysaccharides forming a weak watery gel. 26295400 1 57 theme proteins 177:184 arg1 mucus 113:117 The mucus 109:117 The mucus produced by many marine organisms 109:151 The mucus produced by many marine organisms is a complex mixture of proteins and polysaccharides forming a weak watery gel. 26295400 6 58 theme inorganic 1147:1155 arg1 matter 1157:1162 inorganic matter 1147:1162 inorganic matter (67.1%) 1147:1170 The A. equina mucus is mainly composed by water (96.2% ± 0.3%), whereas its dry weight is made of 24.2% ± 1.3% proteins and 7.8% ± 0.2% carbohydrates, with the smallest and largest components referable to lipids (0.9%) and inorganic matter (67.1%). 26295400 6 58 theme inorganic 1147:1155 arg1 % 1169:1169 67.1% 1165:1169 67.1% 1165:1169 The A. equina mucus is mainly composed by water (96.2% ± 0.3%), whereas its dry weight is made of 24.2% ± 1.3% proteins and 7.8% ± 0.2% carbohydrates, with the smallest and largest components referable to lipids (0.9%) and inorganic matter (67.1%). 26295400 7 59 theme lysozyme-like 1361:1373 arg1 activity 1375:1382 antibacterial lysozyme-like activity 1347:1382 antibacterial lysozyme-like activity 1347:1382 The A. equina mucus matrix exhibited hemolytic activity on rabbit erythrocytes, cytotoxic activity against the tumor cell line K562 (human erythromyeloblastoid leukemia) and antibacterial lysozyme-like activity. 26295400 8 60 theme mucus 1599:1603 arg1 exploitation 1549:1560 exploitation 1549:1560 exploitation of A. equina and other sea anemones' mucus 1549:1603 The findings from this study improve the available information on the mucus composition in invertebrates and have implications for future investigations related to exploitation of A. equina and other sea anemones' mucus as a source of bioactive compounds of high pharmaceutical and biotechnological interest. 26295400 2 61 theme structural 303:312 arg1 support 314:320 structural support 303:320 structural support 303:320 It is essential for vital processes including locomotion, navigation, structural support, heterotrophic feeding and defence against a multitude of environmental stresses, predators, parasites, and pathogens. 26295400 8 62 from information 1436:1446 arg1 composition 1461:1471 the mucus composition 1451:1471 the mucus composition in invertebrates 1451:1488 The findings from this study improve the available information on the mucus composition in invertebrates and have implications for future investigations related to exploitation of A. equina and other sea anemones' mucus as a source of bioactive compounds of high pharmaceutical and biotechnological interest. 26295400 8 63 theme available 1426:1434 arg1 information 1436:1446 the available information 1422:1446 the available information on the mucus composition in invertebrates 1422:1488 The findings from this study improve the available information on the mucus composition in invertebrates and have implications for future investigations related to exploitation of A. equina and other sea anemones' mucus as a source of bioactive compounds of high pharmaceutical and biotechnological interest. 26295400 3 64 theme Actinia 531:537 arg1 anemone 523:529 the sea anemone 515:529 the sea anemone Actinia equina (Linnaeus, 1758) for preventing burial by excess sedimentation and for protection 515:626 In the present study we focused on mucus produced by a benthic cnidarian, the sea anemone Actinia equina (Linnaeus, 1758) for preventing burial by excess sedimentation and for protection. 26295400 3 64 theme Actinia 531:537 arg1 cnidarian 504:512 a benthic cnidarian 494:512 a benthic cnidarian 494:512 In the present study we focused on mucus produced by a benthic cnidarian, the sea anemone Actinia equina (Linnaeus, 1758) for preventing burial by excess sedimentation and for protection. 26295400 6 65 theme ± 1053:1053 arg1 % 1058:1058 7.8% ± 0.2% 1048:1058 7.8% ± 0.2% carbohydrates 1048:1072 The A. equina mucus is mainly composed by water (96.2% ± 0.3%), whereas its dry weight is made of 24.2% ± 1.3% proteins and 7.8% ± 0.2% carbohydrates, with the smallest and largest components referable to lipids (0.9%) and inorganic matter (67.1%). 26295400 7 66 theme erythromyeloblastoid 1312:1331 arg1 K562 1300:1303 the tumor cell line K562 1280:1303 the tumor cell line K562 (human erythromyeloblastoid leukemia) 1280:1341 The A. equina mucus matrix exhibited hemolytic activity on rabbit erythrocytes, cytotoxic activity against the tumor cell line K562 (human erythromyeloblastoid leukemia) and antibacterial lysozyme-like activity. 26295400 7 66 theme erythromyeloblastoid 1312:1331 arg1 leukemia 1333:1340 human erythromyeloblastoid leukemia 1306:1340 human erythromyeloblastoid leukemia 1306:1340 The A. equina mucus matrix exhibited hemolytic activity on rabbit erythrocytes, cytotoxic activity against the tumor cell line K562 (human erythromyeloblastoid leukemia) and antibacterial lysozyme-like activity. 26295400 4 67 theme physico-chemical 657:672 arg1 conductivity 742:753 electrical conductivity 731:753 electrical conductivity 731:753 We investigated some of the physico-chemical properties of this matrix such as viscosity, osmolarity, electrical conductivity, protein, carbohydrate, and total lipid contents. 26295400 4 67 theme physico-chemical 657:672 arg1 viscosity 708:716 viscosity 708:716 viscosity 708:716 We investigated some of the physico-chemical properties of this matrix such as viscosity, osmolarity, electrical conductivity, protein, carbohydrate, and total lipid contents. 26295400 4 67 theme physico-chemical 657:672 arg1 protein 756:762 protein 756:762 protein 756:762 We investigated some of the physico-chemical properties of this matrix such as viscosity, osmolarity, electrical conductivity, protein, carbohydrate, and total lipid contents. 26295400 4 67 theme physico-chemical 657:672 arg1 properties 674:683 the physico-chemical properties 653:683 the physico-chemical properties of this matrix such as viscosity, osmolarity, electrical conductivity, protein, carbohydrate, and total lipid contents 653:802 We investigated some of the physico-chemical properties of this matrix such as viscosity, osmolarity, electrical conductivity, protein, carbohydrate, and total lipid contents. 26295400 4 67 theme physico-chemical 657:672 arg1 contents 795:802 total lipid contents 783:802 total lipid contents 783:802 We investigated some of the physico-chemical properties of this matrix such as viscosity, osmolarity, electrical conductivity, protein, carbohydrate, and total lipid contents. 26295400 4 67 theme physico-chemical 657:672 arg1 carbohydrate 765:776 carbohydrate 765:776 carbohydrate 765:776 We investigated some of the physico-chemical properties of this matrix such as viscosity, osmolarity, electrical conductivity, protein, carbohydrate, and total lipid contents. 26295400 4 67 theme physico-chemical 657:672 arg1 osmolarity 719:728 osmolarity 719:728 osmolarity 719:728 We investigated some of the physico-chemical properties of this matrix such as viscosity, osmolarity, electrical conductivity, protein, carbohydrate, and total lipid contents. 26295400 6 68 theme ± 1028:1028 arg1 % 1033:1033 24.2% ± 1.3% 1022:1033 24.2% ± 1.3% proteins 1022:1042 The A. equina mucus is mainly composed by water (96.2% ± 0.3%), whereas its dry weight is made of 24.2% ± 1.3% proteins and 7.8% ± 0.2% carbohydrates, with the smallest and largest components referable to lipids (0.9%) and inorganic matter (67.1%). 26295400 8 69 from composition 1461:1471 arg1 invertebrates 1476:1488 invertebrates 1476:1488 invertebrates 1476:1488 The findings from this study improve the available information on the mucus composition in invertebrates and have implications for future investigations related to exploitation of A. equina and other sea anemones' mucus as a source of bioactive compounds of high pharmaceutical and biotechnological interest. 26295400 3 70 theme excess 588:593 arg1 sedimentation 595:607 excess sedimentation 588:607 excess sedimentation 588:607 In the present study we focused on mucus produced by a benthic cnidarian, the sea anemone Actinia equina (Linnaeus, 1758) for preventing burial by excess sedimentation and for protection. 26295400 6 71 theme % 1058:1058 arg1 carbohydrates 1060:1072 7.8% ± 0.2% carbohydrates 1048:1072 7.8% ± 0.2% carbohydrates 1048:1072 The A. equina mucus is mainly composed by water (96.2% ± 0.3%), whereas its dry weight is made of 24.2% ± 1.3% proteins and 7.8% ± 0.2% carbohydrates, with the smallest and largest components referable to lipids (0.9%) and inorganic matter (67.1%). 26295400 7 72 from activity 1375:1382 arg1 erythrocytes 1239:1250 rabbit erythrocytes 1232:1250 rabbit erythrocytes 1232:1250 The A. equina mucus matrix exhibited hemolytic activity on rabbit erythrocytes, cytotoxic activity against the tumor cell line K562 (human erythromyeloblastoid leukemia) and antibacterial lysozyme-like activity. 26295400 6 73 theme dry 1000:1002 arg1 weight 1004:1009 its dry weight 996:1009 its dry weight 996:1009 The A. equina mucus is mainly composed by water (96.2% ± 0.3%), whereas its dry weight is made of 24.2% ± 1.3% proteins and 7.8% ± 0.2% carbohydrates, with the smallest and largest components referable to lipids (0.9%) and inorganic matter (67.1%). 26295400 8 74 theme future 1516:1521 arg1 investigations 1523:1536 future investigations 1516:1536 future investigations related to exploitation of A. equina and other sea anemones' mucus 1516:1603 The findings from this study improve the available information on the mucus composition in invertebrates and have implications for future investigations related to exploitation of A. equina and other sea anemones' mucus as a source of bioactive compounds of high pharmaceutical and biotechnological interest. 26295400 1 75 theme polysaccharides 190:204 arg1 mixture 166:172 a complex mixture 156:172 a complex mixture of proteins and polysaccharides forming a weak watery gel 156:230 The mucus produced by many marine organisms is a complex mixture of proteins and polysaccharides forming a weak watery gel. 26295400 1 75 theme polysaccharides 190:204 arg1 mucus 113:117 The mucus 109:117 The mucus produced by many marine organisms 109:151 The mucus produced by many marine organisms is a complex mixture of proteins and polysaccharides forming a weak watery gel. 26295400 7 76 from activity 1263:1270 arg1 erythrocytes 1239:1250 rabbit erythrocytes 1232:1250 rabbit erythrocytes 1232:1250 The A. equina mucus matrix exhibited hemolytic activity on rabbit erythrocytes, cytotoxic activity against the tumor cell line K562 (human erythromyeloblastoid leukemia) and antibacterial lysozyme-like activity. 26295400 0 77 dep Mucus 4:8 arg1 Resource 64:71 An Unexplored Resource 50:71 The Mucus of Actinia equina (Anthozoa, Cnidaria): An Unexplored Resource for Potential Applicative Purposes. 0:107 The Mucus of Actinia equina (Anthozoa, Cnidaria): An Unexplored Resource for Potential Applicative Purposes. 26295400 0 77 dep Mucus 4:8 arg1 Cnidaria 39:46 Cnidaria 39:46 Cnidaria 39:46 The Mucus of Actinia equina (Anthozoa, Cnidaria): An Unexplored Resource for Potential Applicative Purposes. 26295400 0 77 dep Mucus 4:8 arg1 Anthozoa 29:36 Anthozoa 29:36 Anthozoa 29:36 The Mucus of Actinia equina (Anthozoa, Cnidaria): An Unexplored Resource for Potential Applicative Purposes. 26295400 1 78 theme complex 158:164 arg1 mixture 166:172 a complex mixture 156:172 a complex mixture of proteins and polysaccharides forming a weak watery gel 156:230 The mucus produced by many marine organisms is a complex mixture of proteins and polysaccharides forming a weak watery gel. 26295400 1 78 theme complex 158:164 arg1 mucus 113:117 The mucus 109:117 The mucus produced by many marine organisms 109:151 The mucus produced by many marine organisms is a complex mixture of proteins and polysaccharides forming a weak watery gel. 26295400 7 79 from activity 1220:1227 arg1 erythrocytes 1239:1250 rabbit erythrocytes 1232:1250 rabbit erythrocytes 1232:1250 The A. equina mucus matrix exhibited hemolytic activity on rabbit erythrocytes, cytotoxic activity against the tumor cell line K562 (human erythromyeloblastoid leukemia) and antibacterial lysozyme-like activity. 26295400 8 80 theme mucus 1455:1459 arg1 composition 1461:1471 the mucus composition 1451:1471 the mucus composition in invertebrates 1451:1488 The findings from this study improve the available information on the mucus composition in invertebrates and have implications for future investigations related to exploitation of A. equina and other sea anemones' mucus as a source of bioactive compounds of high pharmaceutical and biotechnological interest. 26295400 4 81 theme electrical 731:740 arg1 conductivity 742:753 electrical conductivity 731:753 electrical conductivity 731:753 We investigated some of the physico-chemical properties of this matrix such as viscosity, osmolarity, electrical conductivity, protein, carbohydrate, and total lipid contents. 26295400 2 82 theme heterotrophic 323:335 arg1 feeding 337:343 heterotrophic feeding 323:343 heterotrophic feeding 323:343 It is essential for vital processes including locomotion, navigation, structural support, heterotrophic feeding and defence against a multitude of environmental stresses, predators, parasites, and pathogens. 26295400 8 83 theme related 1538:1544 arg1 investigations 1523:1536 future investigations 1516:1536 future investigations related to exploitation of A. equina and other sea anemones' mucus 1516:1603 The findings from this study improve the available information on the mucus composition in invertebrates and have implications for future investigations related to exploitation of A. equina and other sea anemones' mucus as a source of bioactive compounds of high pharmaceutical and biotechnological interest. 25724745 12 0 theme name 1910:1913 arg1 nov. 1947:1950 the name Planctomicrobium piriforme gen. nov. 1906:1950 the name Planctomicrobium piriforme gen. nov. 1906:1950 Based on these data, the novel isolate should be considered as representing a novel genus and species of planctomycetes, for which the name Planctomicrobium piriforme gen. nov., sp. 25724745 6 1 theme Most 942:945 arg1 sugars 947:952 Most sugars 942:952 Most sugars 942:952 Most sugars, a number of polysaccharides and several organic acids were the preferred growth substrates. 25724745 6 1 theme Most 942:945 arg1 number 957:962 a number 955:962 a number of polysaccharides 955:981 Most sugars, a number of polysaccharides and several organic acids were the preferred growth substrates. 25724745 6 1 theme Most 942:945 arg1 substrates 1035:1044 the preferred growth substrates 1014:1044 the preferred growth substrates 1014:1044 Most sugars, a number of polysaccharides and several organic acids were the preferred growth substrates. 25724745 6 1 theme Most 942:945 arg1 acids 1003:1007 several organic acids 987:1007 several organic acids 987:1007 Most sugars, a number of polysaccharides and several organic acids were the preferred growth substrates. 25724745 11 2 theme characteristics 1758:1772 arg1 pattern 1720:1726 substrate utilization pattern 1698:1726 substrate utilization pattern 1698:1726 Strain P3(T) differed from Planctomyces brasiliensis and Planctomyces maris by cell morphology, substrate utilization pattern and a number of physiological characteristics. 25724745 11 2 theme characteristics 1758:1772 arg1 number 1734:1739 a number 1732:1739 a number of physiological characteristics 1732:1772 Strain P3(T) differed from Planctomyces brasiliensis and Planctomyces maris by cell morphology, substrate utilization pattern and a number of physiological characteristics. 25724745 11 2 theme characteristics 1758:1772 arg1 morphology 1686:1695 cell morphology 1681:1695 cell morphology 1681:1695 Strain P3(T) differed from Planctomyces brasiliensis and Planctomyces maris by cell morphology, substrate utilization pattern and a number of physiological characteristics. 25724745 6 3 theme growth 1028:1033 arg1 sugars 947:952 Most sugars 942:952 Most sugars 942:952 Most sugars, a number of polysaccharides and several organic acids were the preferred growth substrates. 25724745 6 3 theme growth 1028:1033 arg1 number 957:962 a number 955:962 a number of polysaccharides 955:981 Most sugars, a number of polysaccharides and several organic acids were the preferred growth substrates. 25724745 6 3 theme growth 1028:1033 arg1 substrates 1035:1044 the preferred growth substrates 1014:1044 the preferred growth substrates 1014:1044 Most sugars, a number of polysaccharides and several organic acids were the preferred growth substrates. 25724745 6 3 theme growth 1028:1033 arg1 acids 1003:1007 several organic acids 987:1007 several organic acids 987:1007 Most sugars, a number of polysaccharides and several organic acids were the preferred growth substrates. 25724745 2 4 theme Valaam 244:249 arg1 Island 251:256 Valaam Island 244:256 Valaam Island 244:256 An aerobic, budding, non-pigmented and rosette-forming bacterium was isolated from a littoral wetland of a boreal lake located in Valaam Island, northern Russia, and designated strain P3(T). 25724745 4 5 with Planctomyces 614:625 arg1 similarity 654:663 89 and 86% sequence similarity 634:663 89 and 86% sequence similarity to Planctomyces brasiliensis and Planctomyces maris , respectively 634:730 16S rRNA gene sequence analysis confirmed that strain P3(T) was a member of the order Planctomycetales and belonged to a phylogenetic lineage defined by the genus Planctomyces , with 89 and 86% sequence similarity to Planctomyces brasiliensis and Planctomyces maris , respectively. 25724745 2 6 theme located 233:239 arg1 lake 228:231 a boreal lake 219:231 a boreal lake located in Valaam Island, northern Russia, and designated strain P3(T) 219:302 An aerobic, budding, non-pigmented and rosette-forming bacterium was isolated from a littoral wetland of a boreal lake located in Valaam Island, northern Russia, and designated strain P3(T). 25724745 8 7 contain contained 1302:1310 arg2 amounts 1324:1330 significant amounts 1312:1330 significant amounts of C18 : 1ω7c and C18 : 0 1312:1356 The major fatty acids were C16 : 0 and C16 : 1ω7c; the cells also contained significant amounts of C18 : 1ω7c and C18 : 0. 25724745 8 7 contain contained 1302:1310 arg2 C18 1350:1352 C18 1350:1352 C18 1350:1352 The major fatty acids were C16 : 0 and C16 : 1ω7c; the cells also contained significant amounts of C18 : 1ω7c and C18 : 0. 25724745 8 7 contain contained 1302:1310 arg1 cells 1291:1295 the cells 1287:1295 the cells 1287:1295 The major fatty acids were C16 : 0 and C16 : 1ω7c; the cells also contained significant amounts of C18 : 1ω7c and C18 : 0. 25724745 8 7 contain contained 1302:1310 arg2 1ω7c 1341:1344 1ω7c 1341:1344 1ω7c 1341:1344 The major fatty acids were C16 : 0 and C16 : 1ω7c; the cells also contained significant amounts of C18 : 1ω7c and C18 : 0. 25724745 8 7 contain contained 1302:1310 arg2 C18 1335:1337 C18 1335:1337 C18 1335:1337 The major fatty acids were C16 : 0 and C16 : 1ω7c; the cells also contained significant amounts of C18 : 1ω7c and C18 : 0. 25724745 5 8 theme capable 792:798 arg1 organism 783:790 a mildly acidophilic, mesophilic organism 750:790 a mildly acidophilic, mesophilic organism capable of growth 750:808 Strain P3(T) was a mildly acidophilic, mesophilic organism capable of growth at pH values between pH 4.2 and 7.1 (with an optimum at pH 6.0-6.5) and at temperatures between 10 and 30 °C (optimum at 20-28 °C). 25724745 5 8 theme capable 792:798 arg1 P3 740:741 Strain P3 733:741 Strain P3(T) 733:744 Strain P3(T) was a mildly acidophilic, mesophilic organism capable of growth at pH values between pH 4.2 and 7.1 (with an optimum at pH 6.0-6.5) and at temperatures between 10 and 30 °C (optimum at 20-28 °C). 25724745 6 9 theme several 987:993 arg1 sugars 947:952 Most sugars 942:952 Most sugars 942:952 Most sugars, a number of polysaccharides and several organic acids were the preferred growth substrates. 25724745 6 9 theme several 987:993 arg1 number 957:962 a number 955:962 a number of polysaccharides 955:981 Most sugars, a number of polysaccharides and several organic acids were the preferred growth substrates. 25724745 6 9 theme several 987:993 arg1 substrates 1035:1044 the preferred growth substrates 1014:1044 the preferred growth substrates 1014:1044 Most sugars, a number of polysaccharides and several organic acids were the preferred growth substrates. 25724745 6 9 theme several 987:993 arg1 acids 1003:1007 several organic acids 987:1007 several organic acids 987:1007 Most sugars, a number of polysaccharides and several organic acids were the preferred growth substrates. 25724745 12 10 theme novel 1853:1857 arg1 genus 1859:1863 a novel genus 1851:1863 a novel genus 1851:1863 Based on these data, the novel isolate should be considered as representing a novel genus and species of planctomycetes, for which the name Planctomicrobium piriforme gen. nov., sp. 25724745 11 11 theme cell 1681:1684 arg1 morphology 1686:1695 cell morphology 1681:1695 cell morphology 1681:1695 Strain P3(T) differed from Planctomyces brasiliensis and Planctomyces maris by cell morphology, substrate utilization pattern and a number of physiological characteristics. 25724745 5 12 from temperatures 885:896 arg1 organism 783:790 a mildly acidophilic, mesophilic organism 750:790 a mildly acidophilic, mesophilic organism capable of growth 750:808 Strain P3(T) was a mildly acidophilic, mesophilic organism capable of growth at pH values between pH 4.2 and 7.1 (with an optimum at pH 6.0-6.5) and at temperatures between 10 and 30 °C (optimum at 20-28 °C). 25724745 5 12 from temperatures 885:896 arg1 P3 740:741 Strain P3 733:741 Strain P3(T) 733:744 Strain P3(T) was a mildly acidophilic, mesophilic organism capable of growth at pH values between pH 4.2 and 7.1 (with an optimum at pH 6.0-6.5) and at temperatures between 10 and 30 °C (optimum at 20-28 °C). 25724745 11 13 theme substrate 1698:1706 arg1 pattern 1720:1726 substrate utilization pattern 1698:1726 substrate utilization pattern 1698:1726 Strain P3(T) differed from Planctomyces brasiliensis and Planctomyces maris by cell morphology, substrate utilization pattern and a number of physiological characteristics. 25724745 4 14 theme phylogenetic 572:583 arg1 lineage 585:591 a phylogenetic lineage 570:591 a phylogenetic lineage defined by the genus Planctomyces , with 89 and 86% sequence similarity to Planctomyces brasiliensis and Planctomyces maris , respectively 570:730 16S rRNA gene sequence analysis confirmed that strain P3(T) was a member of the order Planctomycetales and belonged to a phylogenetic lineage defined by the genus Planctomyces , with 89 and 86% sequence similarity to Planctomyces brasiliensis and Planctomyces maris , respectively. 25724745 9 15 theme C31 1513:1515 arg1 hydrocarbon 1521:1531 C31 : 9 hydrocarbon 1513:1531 C31 : 9 hydrocarbon 1513:1531 The major intact polar lipids were diacylglycerol-O-(N,N,N-trimethyl)homoserine (DGTS) lipids; the major neutral lipids were long-chain 1,(ω-1)-diols and C31 : 9 hydrocarbon. 25724745 5 16 theme acidophilic 759:769 arg1 organism 783:790 a mildly acidophilic, mesophilic organism 750:790 a mildly acidophilic, mesophilic organism capable of growth 750:808 Strain P3(T) was a mildly acidophilic, mesophilic organism capable of growth at pH values between pH 4.2 and 7.1 (with an optimum at pH 6.0-6.5) and at temperatures between 10 and 30 °C (optimum at 20-28 °C). 25724745 5 16 theme acidophilic 759:769 arg1 P3 740:741 Strain P3 733:741 Strain P3(T) 733:744 Strain P3(T) was a mildly acidophilic, mesophilic organism capable of growth at pH values between pH 4.2 and 7.1 (with an optimum at pH 6.0-6.5) and at temperatures between 10 and 30 °C (optimum at 20-28 °C). 25724745 7 17 theme NaCl 1198:1201 arg1 concentrations 1203:1216 NaCl concentrations 1198:1216 NaCl concentrations above 0.5% (w/v) 1198:1233 Compared with Planctomyces brasiliensis and Planctomyces maris , which require NaCl for growth, strain P3(T) was salt-sensitive and did not develop at NaCl concentrations above 0.5% (w/v). 25724745 9 18 theme major 1458:1462 arg1 long-chain 1484:1493 long-chain 1 1484:1495 long-chain 1 1484:1495 The major intact polar lipids were diacylglycerol-O-(N,N,N-trimethyl)homoserine (DGTS) lipids; the major neutral lipids were long-chain 1,(ω-1)-diols and C31 : 9 hydrocarbon. 25724745 9 18 theme major 1458:1462 arg1 lipids 1472:1477 the major neutral lipids 1454:1477 the major neutral lipids 1454:1477 The major intact polar lipids were diacylglycerol-O-(N,N,N-trimethyl)homoserine (DGTS) lipids; the major neutral lipids were long-chain 1,(ω-1)-diols and C31 : 9 hydrocarbon. 25724745 2 19 theme boreal 221:226 arg1 lake 228:231 a boreal lake 219:231 a boreal lake located in Valaam Island, northern Russia, and designated strain P3(T) 219:302 An aerobic, budding, non-pigmented and rosette-forming bacterium was isolated from a littoral wetland of a boreal lake located in Valaam Island, northern Russia, and designated strain P3(T). 25724745 1 20 theme lake 108:111 arg1 wetland 88:94 a littoral wetland 77:94 a littoral wetland of a boreal lake 77:111 nov., a stalked planctomycete from a littoral wetland of a boreal lake. 25724745 2 21 from Island 251:256 arg1 located 233:239 located 233:239 located 233:239 An aerobic, budding, non-pigmented and rosette-forming bacterium was isolated from a littoral wetland of a boreal lake located in Valaam Island, northern Russia, and designated strain P3(T). 25724745 1 22 theme boreal 101:106 arg1 lake 108:111 a boreal lake 99:111 a boreal lake 99:111 nov., a stalked planctomycete from a littoral wetland of a boreal lake. 25724745 5 23 theme growth 803:808 arg1 capable 792:798 capable 792:798 capable 792:798 Strain P3(T) was a mildly acidophilic, mesophilic organism capable of growth at pH values between pH 4.2 and 7.1 (with an optimum at pH 6.0-6.5) and at temperatures between 10 and 30 °C (optimum at 20-28 °C). 25724745 4 24 theme 16S 451:453 arg1 rRNA 455:458 16S rRNA 451:458 16S rRNA gene sequence analysis 451:481 16S rRNA gene sequence analysis confirmed that strain P3(T) was a member of the order Planctomycetales and belonged to a phylogenetic lineage defined by the genus Planctomyces , with 89 and 86% sequence similarity to Planctomyces brasiliensis and Planctomyces maris , respectively. 25724745 5 25 theme pH 813:814 arg1 values 816:821 pH values 813:821 pH values between pH 4.2 and 7.1 (with an optimum at pH 6.0-6.5) 813:876 Strain P3(T) was a mildly acidophilic, mesophilic organism capable of growth at pH values between pH 4.2 and 7.1 (with an optimum at pH 6.0-6.5) and at temperatures between 10 and 30 °C (optimum at 20-28 °C). 25724745 4 26 theme gene 460:463 arg1 analysis 474:481 16S rRNA gene sequence analysis 451:481 16S rRNA gene sequence analysis 451:481 16S rRNA gene sequence analysis confirmed that strain P3(T) was a member of the order Planctomycetales and belonged to a phylogenetic lineage defined by the genus Planctomyces , with 89 and 86% sequence similarity to Planctomyces brasiliensis and Planctomyces maris , respectively. 25724745 12 27 theme planctomycetes 1880:1893 arg1 species 1869:1875 species 1869:1875 species of planctomycetes 1869:1893 Based on these data, the novel isolate should be considered as representing a novel genus and species of planctomycetes, for which the name Planctomicrobium piriforme gen. nov., sp. 25724745 12 27 theme planctomycetes 1880:1893 arg1 genus 1859:1863 a novel genus 1851:1863 a novel genus 1851:1863 Based on these data, the novel isolate should be considered as representing a novel genus and species of planctomycetes, for which the name Planctomicrobium piriforme gen. nov., sp. 25724745 9 28 theme ω-1 1498:1500 arg1 -diols 1502:1507 (ω-1)-diols 1497:1507 (ω-1)-diols 1497:1507 The major intact polar lipids were diacylglycerol-O-(N,N,N-trimethyl)homoserine (DGTS) lipids; the major neutral lipids were long-chain 1,(ω-1)-diols and C31 : 9 hydrocarbon. 25724745 5 29 with pH 831:832 arg1 optimum 855:861 an optimum 852:861 an optimum at pH 6.0-6.5 852:875 Strain P3(T) was a mildly acidophilic, mesophilic organism capable of growth at pH values between pH 4.2 and 7.1 (with an optimum at pH 6.0-6.5) and at temperatures between 10 and 30 °C (optimum at 20-28 °C). 25724745 3 30 theme crateriform 374:384 arg1 pits 386:389 crateriform pits 374:389 crateriform pits 374:389 Ellipsoidal to pear-shaped cells of this bacterium were covered with crateriform pits and possessed stalks suggesting a planctomycete morphotype. 25724745 2 31 attach isolated 183:190 arg2 bacterium 169:177 An aerobic, budding, non-pigmented and rosette-forming bacterium 114:177 An aerobic, budding, non-pigmented and rosette-forming bacterium 114:177 An aerobic, budding, non-pigmented and rosette-forming bacterium was isolated from a littoral wetland of a boreal lake located in Valaam Island, northern Russia, and designated strain P3(T). 25724745 2 31 attach isolated 183:190 arg1 wetland 208:214 a littoral wetland 197:214 a littoral wetland of a boreal lake located in Valaam Island, northern Russia, and designated strain P3(T) 197:302 An aerobic, budding, non-pigmented and rosette-forming bacterium was isolated from a littoral wetland of a boreal lake located in Valaam Island, northern Russia, and designated strain P3(T). 25724745 3 32 theme pear-shaped 320:330 arg1 cells 332:336 Ellipsoidal to pear-shaped cells 305:336 Ellipsoidal to pear-shaped cells of this bacterium 305:354 Ellipsoidal to pear-shaped cells of this bacterium were covered with crateriform pits and possessed stalks suggesting a planctomycete morphotype. 25724745 8 33 theme significant 1312:1322 arg1 C18 1350:1352 C18 1350:1352 C18 1350:1352 The major fatty acids were C16 : 0 and C16 : 1ω7c; the cells also contained significant amounts of C18 : 1ω7c and C18 : 0. 25724745 8 33 theme significant 1312:1322 arg1 1ω7c 1341:1344 1ω7c 1341:1344 1ω7c 1341:1344 The major fatty acids were C16 : 0 and C16 : 1ω7c; the cells also contained significant amounts of C18 : 1ω7c and C18 : 0. 25724745 8 33 theme significant 1312:1322 arg1 C18 1335:1337 C18 1335:1337 C18 1335:1337 The major fatty acids were C16 : 0 and C16 : 1ω7c; the cells also contained significant amounts of C18 : 1ω7c and C18 : 0. 25724745 8 33 theme significant 1312:1322 arg1 amounts 1324:1330 significant amounts 1312:1330 significant amounts of C18 : 1ω7c and C18 : 0 1312:1356 The major fatty acids were C16 : 0 and C16 : 1ω7c; the cells also contained significant amounts of C18 : 1ω7c and C18 : 0. 25724745 5 34 from values 816:821 arg1 organism 783:790 a mildly acidophilic, mesophilic organism 750:790 a mildly acidophilic, mesophilic organism capable of growth 750:808 Strain P3(T) was a mildly acidophilic, mesophilic organism capable of growth at pH values between pH 4.2 and 7.1 (with an optimum at pH 6.0-6.5) and at temperatures between 10 and 30 °C (optimum at 20-28 °C). 25724745 5 34 from values 816:821 arg1 P3 740:741 Strain P3 733:741 Strain P3(T) 733:744 Strain P3(T) was a mildly acidophilic, mesophilic organism capable of growth at pH values between pH 4.2 and 7.1 (with an optimum at pH 6.0-6.5) and at temperatures between 10 and 30 °C (optimum at 20-28 °C). 25724745 3 35 theme Ellipsoidal 305:315 arg1 cells 332:336 Ellipsoidal to pear-shaped cells 305:336 Ellipsoidal to pear-shaped cells of this bacterium 305:354 Ellipsoidal to pear-shaped cells of this bacterium were covered with crateriform pits and possessed stalks suggesting a planctomycete morphotype. 25724745 7 36 dep Planctomyces 1061:1072 arg1 brasiliensis 1074:1085 Planctomyces brasiliensis 1061:1085 Planctomyces brasiliensis 1061:1085 Compared with Planctomyces brasiliensis and Planctomyces maris , which require NaCl for growth, strain P3(T) was salt-sensitive and did not develop at NaCl concentrations above 0.5% (w/v). 25724745 0 37 theme gen. 27:30 arg1 sp 38:39 sp 38:39 sp 38:39 Planctomicrobium piriforme gen. nov., sp. 25724745 0 37 theme gen. 27:30 arg1 nov. 32:35 gen. nov. 27:35 gen. nov. 27:35 Planctomicrobium piriforme gen. nov., sp. 25724745 11 38 dep Planctomyces 1659:1670 arg1 maris 1672:1676 Planctomyces maris 1659:1676 Planctomyces maris 1659:1676 Strain P3(T) differed from Planctomyces brasiliensis and Planctomyces maris by cell morphology, substrate utilization pattern and a number of physiological characteristics. 25724745 3 39 theme bacterium 346:354 arg1 cells 332:336 Ellipsoidal to pear-shaped cells 305:336 Ellipsoidal to pear-shaped cells of this bacterium 305:354 Ellipsoidal to pear-shaped cells of this bacterium were covered with crateriform pits and possessed stalks suggesting a planctomycete morphotype. 25724745 2 40 theme non-pigmented 135:147 arg1 bacterium 169:177 An aerobic, budding, non-pigmented and rosette-forming bacterium 114:177 An aerobic, budding, non-pigmented and rosette-forming bacterium 114:177 An aerobic, budding, non-pigmented and rosette-forming bacterium was isolated from a littoral wetland of a boreal lake located in Valaam Island, northern Russia, and designated strain P3(T). 25724745 2 41 theme budding 126:132 arg1 bacterium 169:177 An aerobic, budding, non-pigmented and rosette-forming bacterium 114:177 An aerobic, budding, non-pigmented and rosette-forming bacterium 114:177 An aerobic, budding, non-pigmented and rosette-forming bacterium was isolated from a littoral wetland of a boreal lake located in Valaam Island, northern Russia, and designated strain P3(T). 25724745 10 42 theme mol 1596:1598 arg1 % 1599:1599 59.0 mol% 1591:1599 59.0 mol% 1591:1599 The quinone was MK-6, and the G+C content of the DNA was 59.0 mol%. 25724745 10 42 theme mol 1596:1598 arg1 content 1568:1574 the G+C content 1560:1574 the G+C content of the DNA 1560:1585 The quinone was MK-6, and the G+C content of the DNA was 59.0 mol%. 25724745 5 43 theme Strain 733:738 arg1 organism 783:790 a mildly acidophilic, mesophilic organism 750:790 a mildly acidophilic, mesophilic organism capable of growth 750:808 Strain P3(T) was a mildly acidophilic, mesophilic organism capable of growth at pH values between pH 4.2 and 7.1 (with an optimum at pH 6.0-6.5) and at temperatures between 10 and 30 °C (optimum at 20-28 °C). 25724745 5 43 theme Strain 733:738 arg1 T 743:743 T 743:743 T 743:743 Strain P3(T) was a mildly acidophilic, mesophilic organism capable of growth at pH values between pH 4.2 and 7.1 (with an optimum at pH 6.0-6.5) and at temperatures between 10 and 30 °C (optimum at 20-28 °C). 25724745 5 43 theme Strain 733:738 arg1 P3 740:741 Strain P3 733:741 Strain P3(T) 733:744 Strain P3(T) was a mildly acidophilic, mesophilic organism capable of growth at pH values between pH 4.2 and 7.1 (with an optimum at pH 6.0-6.5) and at temperatures between 10 and 30 °C (optimum at 20-28 °C). 25724745 12 44 theme gen. 1942:1945 arg1 nov. 1947:1950 the name Planctomicrobium piriforme gen. nov. 1906:1950 the name Planctomicrobium piriforme gen. nov. 1906:1950 Based on these data, the novel isolate should be considered as representing a novel genus and species of planctomycetes, for which the name Planctomicrobium piriforme gen. nov., sp. 25724745 9 45 theme intact 1369:1374 arg1 lipids 1382:1387 The major intact polar lipids 1359:1387 The major intact polar lipids 1359:1387 The major intact polar lipids were diacylglycerol-O-(N,N,N-trimethyl)homoserine (DGTS) lipids; the major neutral lipids were long-chain 1,(ω-1)-diols and C31 : 9 hydrocarbon. 25724745 9 45 theme intact 1369:1374 arg1 lipids 1446:1451 diacylglycerol-O-(N,N,N-trimethyl)homoserine (DGTS) lipids 1394:1451 diacylglycerol-O-(N,N,N-trimethyl)homoserine (DGTS) lipids 1394:1451 The major intact polar lipids were diacylglycerol-O-(N,N,N-trimethyl)homoserine (DGTS) lipids; the major neutral lipids were long-chain 1,(ω-1)-diols and C31 : 9 hydrocarbon. 25724745 10 46 theme G+C 1564:1566 arg1 % 1599:1599 59.0 mol% 1591:1599 59.0 mol% 1591:1599 The quinone was MK-6, and the G+C content of the DNA was 59.0 mol%. 25724745 10 46 theme G+C 1564:1566 arg1 content 1568:1574 the G+C content 1560:1574 the G+C content of the DNA 1560:1585 The quinone was MK-6, and the G+C content of the DNA was 59.0 mol%. 25724745 2 47 theme designated 280:289 arg1 T 301:301 T 301:301 T 301:301 An aerobic, budding, non-pigmented and rosette-forming bacterium was isolated from a littoral wetland of a boreal lake located in Valaam Island, northern Russia, and designated strain P3(T). 25724745 2 47 theme designated 280:289 arg1 P3 298:299 designated strain P3 280:299 designated strain P3(T) 280:302 An aerobic, budding, non-pigmented and rosette-forming bacterium was isolated from a littoral wetland of a boreal lake located in Valaam Island, northern Russia, and designated strain P3(T). 25724745 1 48 from wetland 88:94 arg1 planctomycete 58:70 planctomycete 58:70 planctomycete 58:70 nov., a stalked planctomycete from a littoral wetland of a boreal lake. 25724745 1 48 from wetland 88:94 arg1 nov. 42:45 nov. 42:45 nov. 42:45 nov., a stalked planctomycete from a littoral wetland of a boreal lake. 25724745 8 49 dep amounts 1324:1330 arg1 C18 1350:1352 C18 1350:1352 C18 1350:1352 The major fatty acids were C16 : 0 and C16 : 1ω7c; the cells also contained significant amounts of C18 : 1ω7c and C18 : 0. 25724745 8 49 dep amounts 1324:1330 arg1 1ω7c 1341:1344 1ω7c 1341:1344 1ω7c 1341:1344 The major fatty acids were C16 : 0 and C16 : 1ω7c; the cells also contained significant amounts of C18 : 1ω7c and C18 : 0. 25724745 8 49 dep amounts 1324:1330 arg1 amounts 1324:1330 significant amounts 1312:1330 significant amounts of C18 : 1ω7c and C18 : 0 1312:1356 The major fatty acids were C16 : 0 and C16 : 1ω7c; the cells also contained significant amounts of C18 : 1ω7c and C18 : 0. 25724745 8 49 dep amounts 1324:1330 arg1 C18 1335:1337 C18 1335:1337 C18 1335:1337 The major fatty acids were C16 : 0 and C16 : 1ω7c; the cells also contained significant amounts of C18 : 1ω7c and C18 : 0. 25724745 8 49 dep amounts 1324:1330 arg1 0 1356:1356 0 1356:1356 0 1356:1356 The major fatty acids were C16 : 0 and C16 : 1ω7c; the cells also contained significant amounts of C18 : 1ω7c and C18 : 0. 25724745 2 50 theme rosette-forming 153:167 arg1 bacterium 169:177 An aerobic, budding, non-pigmented and rosette-forming bacterium 114:177 An aerobic, budding, non-pigmented and rosette-forming bacterium 114:177 An aerobic, budding, non-pigmented and rosette-forming bacterium was isolated from a littoral wetland of a boreal lake located in Valaam Island, northern Russia, and designated strain P3(T). 25724745 8 51 theme fatty 1246:1250 arg1 C16 1263:1265 C16 1263:1265 C16 1263:1265 The major fatty acids were C16 : 0 and C16 : 1ω7c; the cells also contained significant amounts of C18 : 1ω7c and C18 : 0. 25724745 8 51 theme fatty 1246:1250 arg1 acids 1252:1256 The major fatty acids 1236:1256 The major fatty acids 1236:1256 The major fatty acids were C16 : 0 and C16 : 1ω7c; the cells also contained significant amounts of C18 : 1ω7c and C18 : 0. 25724745 9 52 theme diacylglycerol-O- 1394:1410 arg1 lipids 1382:1387 The major intact polar lipids 1359:1387 The major intact polar lipids 1359:1387 The major intact polar lipids were diacylglycerol-O-(N,N,N-trimethyl)homoserine (DGTS) lipids; the major neutral lipids were long-chain 1,(ω-1)-diols and C31 : 9 hydrocarbon. 25724745 9 52 theme diacylglycerol-O- 1394:1410 arg1 lipids 1446:1451 diacylglycerol-O-(N,N,N-trimethyl)homoserine (DGTS) lipids 1394:1451 diacylglycerol-O-(N,N,N-trimethyl)homoserine (DGTS) lipids 1394:1451 The major intact polar lipids were diacylglycerol-O-(N,N,N-trimethyl)homoserine (DGTS) lipids; the major neutral lipids were long-chain 1,(ω-1)-diols and C31 : 9 hydrocarbon. 25724745 4 53 theme Planctomycetales 537:552 arg1 member 517:522 a member 515:522 a member of the order Planctomycetales 515:552 16S rRNA gene sequence analysis confirmed that strain P3(T) was a member of the order Planctomycetales and belonged to a phylogenetic lineage defined by the genus Planctomyces , with 89 and 86% sequence similarity to Planctomyces brasiliensis and Planctomyces maris , respectively. 25724745 4 53 theme Planctomycetales 537:552 arg1 P3 505:506 strain P3 498:506 strain P3(T) 498:509 16S rRNA gene sequence analysis confirmed that strain P3(T) was a member of the order Planctomycetales and belonged to a phylogenetic lineage defined by the genus Planctomyces , with 89 and 86% sequence similarity to Planctomyces brasiliensis and Planctomyces maris , respectively. 25724745 10 54 theme DNA 1583:1585 arg1 % 1599:1599 59.0 mol% 1591:1599 59.0 mol% 1591:1599 The quinone was MK-6, and the G+C content of the DNA was 59.0 mol%. 25724745 10 54 theme DNA 1583:1585 arg1 content 1568:1574 the G+C content 1560:1574 the G+C content of the DNA 1560:1585 The quinone was MK-6, and the G+C content of the DNA was 59.0 mol%. 25724745 5 55 from pH 866:867 arg1 optimum 855:861 an optimum 852:861 an optimum at pH 6.0-6.5 852:875 Strain P3(T) was a mildly acidophilic, mesophilic organism capable of growth at pH values between pH 4.2 and 7.1 (with an optimum at pH 6.0-6.5) and at temperatures between 10 and 30 °C (optimum at 20-28 °C). 25724745 12 56 theme piriforme 1932:1940 arg1 nov. 1947:1950 the name Planctomicrobium piriforme gen. nov. 1906:1950 the name Planctomicrobium piriforme gen. nov. 1906:1950 Based on these data, the novel isolate should be considered as representing a novel genus and species of planctomycetes, for which the name Planctomicrobium piriforme gen. nov., sp. 25724745 2 57 from P3 298:299 arg1 located 233:239 located 233:239 located 233:239 An aerobic, budding, non-pigmented and rosette-forming bacterium was isolated from a littoral wetland of a boreal lake located in Valaam Island, northern Russia, and designated strain P3(T). 25724745 6 58 theme preferred 1018:1026 arg1 sugars 947:952 Most sugars 942:952 Most sugars 942:952 Most sugars, a number of polysaccharides and several organic acids were the preferred growth substrates. 25724745 6 58 theme preferred 1018:1026 arg1 number 957:962 a number 955:962 a number of polysaccharides 955:981 Most sugars, a number of polysaccharides and several organic acids were the preferred growth substrates. 25724745 6 58 theme preferred 1018:1026 arg1 substrates 1035:1044 the preferred growth substrates 1014:1044 the preferred growth substrates 1014:1044 Most sugars, a number of polysaccharides and several organic acids were the preferred growth substrates. 25724745 6 58 theme preferred 1018:1026 arg1 acids 1003:1007 several organic acids 987:1007 several organic acids 987:1007 Most sugars, a number of polysaccharides and several organic acids were the preferred growth substrates. 25724745 2 59 theme aerobic 117:123 arg1 bacterium 169:177 An aerobic, budding, non-pigmented and rosette-forming bacterium 114:177 An aerobic, budding, non-pigmented and rosette-forming bacterium 114:177 An aerobic, budding, non-pigmented and rosette-forming bacterium was isolated from a littoral wetland of a boreal lake located in Valaam Island, northern Russia, and designated strain P3(T). 25724745 9 60 theme homoserine 1428:1437 arg1 lipids 1382:1387 The major intact polar lipids 1359:1387 The major intact polar lipids 1359:1387 The major intact polar lipids were diacylglycerol-O-(N,N,N-trimethyl)homoserine (DGTS) lipids; the major neutral lipids were long-chain 1,(ω-1)-diols and C31 : 9 hydrocarbon. 25724745 9 60 theme homoserine 1428:1437 arg1 lipids 1446:1451 diacylglycerol-O-(N,N,N-trimethyl)homoserine (DGTS) lipids 1394:1451 diacylglycerol-O-(N,N,N-trimethyl)homoserine (DGTS) lipids 1394:1451 The major intact polar lipids were diacylglycerol-O-(N,N,N-trimethyl)homoserine (DGTS) lipids; the major neutral lipids were long-chain 1,(ω-1)-diols and C31 : 9 hydrocarbon. 25724745 6 61 theme organic 995:1001 arg1 sugars 947:952 Most sugars 942:952 Most sugars 942:952 Most sugars, a number of polysaccharides and several organic acids were the preferred growth substrates. 25724745 6 61 theme organic 995:1001 arg1 number 957:962 a number 955:962 a number of polysaccharides 955:981 Most sugars, a number of polysaccharides and several organic acids were the preferred growth substrates. 25724745 6 61 theme organic 995:1001 arg1 substrates 1035:1044 the preferred growth substrates 1014:1044 the preferred growth substrates 1014:1044 Most sugars, a number of polysaccharides and several organic acids were the preferred growth substrates. 25724745 6 61 theme organic 995:1001 arg1 acids 1003:1007 several organic acids 987:1007 several organic acids 987:1007 Most sugars, a number of polysaccharides and several organic acids were the preferred growth substrates. 25724745 14 62 theme type 1980:1983 arg1 P3 1995:1996 P3 1995:1996 P3(T) ( =DSM 26348(T) =VKM B-2887(T)) 1995:2031 The type strain is P3(T) ( =DSM 26348(T) =VKM B-2887(T)). 25724745 14 62 theme type 1980:1983 arg1 strain 1985:1990 The type strain 1976:1990 The type strain 1976:1990 The type strain is P3(T) ( =DSM 26348(T) =VKM B-2887(T)). 25724745 2 63 theme northern 259:266 arg1 Russia 268:273 northern Russia 259:273 northern Russia 259:273 An aerobic, budding, non-pigmented and rosette-forming bacterium was isolated from a littoral wetland of a boreal lake located in Valaam Island, northern Russia, and designated strain P3(T). 25724745 9 64 theme DGTS 1440:1443 arg1 lipids 1382:1387 The major intact polar lipids 1359:1387 The major intact polar lipids 1359:1387 The major intact polar lipids were diacylglycerol-O-(N,N,N-trimethyl)homoserine (DGTS) lipids; the major neutral lipids were long-chain 1,(ω-1)-diols and C31 : 9 hydrocarbon. 25724745 9 64 theme DGTS 1440:1443 arg1 lipids 1446:1451 diacylglycerol-O-(N,N,N-trimethyl)homoserine (DGTS) lipids 1394:1451 diacylglycerol-O-(N,N,N-trimethyl)homoserine (DGTS) lipids 1394:1451 The major intact polar lipids were diacylglycerol-O-(N,N,N-trimethyl)homoserine (DGTS) lipids; the major neutral lipids were long-chain 1,(ω-1)-diols and C31 : 9 hydrocarbon. 25724745 9 65 dep diacylglycerol-O- 1394:1410 arg1 N-trimethyl 1416:1426 N-trimethyl 1416:1426 N-trimethyl 1416:1426 The major intact polar lipids were diacylglycerol-O-(N,N,N-trimethyl)homoserine (DGTS) lipids; the major neutral lipids were long-chain 1,(ω-1)-diols and C31 : 9 hydrocarbon. 25724745 9 65 dep diacylglycerol-O- 1394:1410 arg1 N 1414:1414 N 1414:1414 N 1414:1414 The major intact polar lipids were diacylglycerol-O-(N,N,N-trimethyl)homoserine (DGTS) lipids; the major neutral lipids were long-chain 1,(ω-1)-diols and C31 : 9 hydrocarbon. 25724745 9 65 dep diacylglycerol-O- 1394:1410 arg1 N 1412:1412 N 1412:1412 N 1412:1412 The major intact polar lipids were diacylglycerol-O-(N,N,N-trimethyl)homoserine (DGTS) lipids; the major neutral lipids were long-chain 1,(ω-1)-diols and C31 : 9 hydrocarbon. 25724745 11 66 theme utilization 1708:1718 arg1 pattern 1720:1726 substrate utilization pattern 1698:1726 substrate utilization pattern 1698:1726 Strain P3(T) differed from Planctomyces brasiliensis and Planctomyces maris by cell morphology, substrate utilization pattern and a number of physiological characteristics. 25724745 11 67 theme Strain 1602:1607 arg1 T 1612:1612 T 1612:1612 T 1612:1612 Strain P3(T) differed from Planctomyces brasiliensis and Planctomyces maris by cell morphology, substrate utilization pattern and a number of physiological characteristics. 25724745 11 67 theme Strain 1602:1607 arg1 P3 1609:1610 Strain P3 1602:1610 Strain P3(T) 1602:1613 Strain P3(T) differed from Planctomyces brasiliensis and Planctomyces maris by cell morphology, substrate utilization pattern and a number of physiological characteristics. 25724745 11 68 theme physiological 1744:1756 arg1 characteristics 1758:1772 physiological characteristics 1744:1772 physiological characteristics 1744:1772 Strain P3(T) differed from Planctomyces brasiliensis and Planctomyces maris by cell morphology, substrate utilization pattern and a number of physiological characteristics. 25724745 2 69 theme lake 228:231 arg1 wetland 208:214 a littoral wetland 197:214 a littoral wetland of a boreal lake located in Valaam Island, northern Russia, and designated strain P3(T) 197:302 An aerobic, budding, non-pigmented and rosette-forming bacterium was isolated from a littoral wetland of a boreal lake located in Valaam Island, northern Russia, and designated strain P3(T). 25724745 4 70 dep similarity 654:663 arg1 % 643:643 % 643:643 % 643:643 16S rRNA gene sequence analysis confirmed that strain P3(T) was a member of the order Planctomycetales and belonged to a phylogenetic lineage defined by the genus Planctomyces , with 89 and 86% sequence similarity to Planctomyces brasiliensis and Planctomyces maris , respectively. 25724745 2 71 from located 233:239 arg1 P3 298:299 designated strain P3 280:299 designated strain P3(T) 280:302 An aerobic, budding, non-pigmented and rosette-forming bacterium was isolated from a littoral wetland of a boreal lake located in Valaam Island, northern Russia, and designated strain P3(T). 25724745 2 71 from located 233:239 arg1 Island 251:256 Valaam Island 244:256 Valaam Island 244:256 An aerobic, budding, non-pigmented and rosette-forming bacterium was isolated from a littoral wetland of a boreal lake located in Valaam Island, northern Russia, and designated strain P3(T). 25724745 2 71 from located 233:239 arg1 Russia 268:273 northern Russia 259:273 northern Russia 259:273 An aerobic, budding, non-pigmented and rosette-forming bacterium was isolated from a littoral wetland of a boreal lake located in Valaam Island, northern Russia, and designated strain P3(T). 25724745 2 71 from located 233:239 arg1 T 301:301 T 301:301 T 301:301 An aerobic, budding, non-pigmented and rosette-forming bacterium was isolated from a littoral wetland of a boreal lake located in Valaam Island, northern Russia, and designated strain P3(T). 25724745 9 72 theme neutral 1464:1470 arg1 long-chain 1484:1493 long-chain 1 1484:1495 long-chain 1 1484:1495 The major intact polar lipids were diacylglycerol-O-(N,N,N-trimethyl)homoserine (DGTS) lipids; the major neutral lipids were long-chain 1,(ω-1)-diols and C31 : 9 hydrocarbon. 25724745 9 72 theme neutral 1464:1470 arg1 lipids 1472:1477 the major neutral lipids 1454:1477 the major neutral lipids 1454:1477 The major intact polar lipids were diacylglycerol-O-(N,N,N-trimethyl)homoserine (DGTS) lipids; the major neutral lipids were long-chain 1,(ω-1)-diols and C31 : 9 hydrocarbon. 25724745 5 73 theme optimum 920:926 arg1 °C 916:917 10 and 30 °C 906:917 10 and 30 °C (optimum at 20-28 °C) 906:939 Strain P3(T) was a mildly acidophilic, mesophilic organism capable of growth at pH values between pH 4.2 and 7.1 (with an optimum at pH 6.0-6.5) and at temperatures between 10 and 30 °C (optimum at 20-28 °C). 25724745 4 74 theme rRNA 455:458 arg1 analysis 474:481 16S rRNA gene sequence analysis 451:481 16S rRNA gene sequence analysis 451:481 16S rRNA gene sequence analysis confirmed that strain P3(T) was a member of the order Planctomycetales and belonged to a phylogenetic lineage defined by the genus Planctomyces , with 89 and 86% sequence similarity to Planctomyces brasiliensis and Planctomyces maris , respectively. 25724745 4 75 theme genus 608:612 arg1 Planctomyces 614:625 the genus Planctomyces 604:625 the genus Planctomyces 604:625 16S rRNA gene sequence analysis confirmed that strain P3(T) was a member of the order Planctomycetales and belonged to a phylogenetic lineage defined by the genus Planctomyces , with 89 and 86% sequence similarity to Planctomyces brasiliensis and Planctomyces maris , respectively. 25724745 4 76 theme sequence 465:472 arg1 analysis 474:481 16S rRNA gene sequence analysis 451:481 16S rRNA gene sequence analysis 451:481 16S rRNA gene sequence analysis confirmed that strain P3(T) was a member of the order Planctomycetales and belonged to a phylogenetic lineage defined by the genus Planctomyces , with 89 and 86% sequence similarity to Planctomyces brasiliensis and Planctomyces maris , respectively. 25724745 5 77 from °C 937:938 arg1 optimum 920:926 optimum 920:926 optimum 920:926 Strain P3(T) was a mildly acidophilic, mesophilic organism capable of growth at pH values between pH 4.2 and 7.1 (with an optimum at pH 6.0-6.5) and at temperatures between 10 and 30 °C (optimum at 20-28 °C). 25724745 12 78 theme novel 1800:1804 arg1 isolate 1806:1812 the novel isolate 1796:1812 the novel isolate 1796:1812 Based on these data, the novel isolate should be considered as representing a novel genus and species of planctomycetes, for which the name Planctomicrobium piriforme gen. nov., sp. 25724745 2 79 from Russia 268:273 arg1 located 233:239 located 233:239 located 233:239 An aerobic, budding, non-pigmented and rosette-forming bacterium was isolated from a littoral wetland of a boreal lake located in Valaam Island, northern Russia, and designated strain P3(T). 25724745 3 80 dep cells 332:336 arg1 to 317:318 to 317:318 to 317:318 Ellipsoidal to pear-shaped cells of this bacterium were covered with crateriform pits and possessed stalks suggesting a planctomycete morphotype. 25724745 14 81 dep P3 1995:1996 arg1 T 2029:2029 T 2029:2029 T 2029:2029 The type strain is P3(T) ( =DSM 26348(T) =VKM B-2887(T)). 25724745 14 81 dep P3 1995:1996 arg1 B-2887 2022:2027  =DSM 26348(T) =VKM B-2887 2002:2027  =DSM 26348(T) =VKM B-2887(T) 2002:2030 The type strain is P3(T) ( =DSM 26348(T) =VKM B-2887(T)). 25724745 12 82 theme Planctomicrobium 1915:1930 arg1 nov. 1947:1950 the name Planctomicrobium piriforme gen. nov. 1906:1950 the name Planctomicrobium piriforme gen. nov. 1906:1950 Based on these data, the novel isolate should be considered as representing a novel genus and species of planctomycetes, for which the name Planctomicrobium piriforme gen. nov., sp. 25724745 4 83 dep % 643:643 arg1 86 641:642 86 641:642 86 641:642 16S rRNA gene sequence analysis confirmed that strain P3(T) was a member of the order Planctomycetales and belonged to a phylogenetic lineage defined by the genus Planctomyces , with 89 and 86% sequence similarity to Planctomyces brasiliensis and Planctomyces maris , respectively. 25724745 4 83 dep % 643:643 arg1 89 634:635 89 634:635 89 634:635 16S rRNA gene sequence analysis confirmed that strain P3(T) was a member of the order Planctomycetales and belonged to a phylogenetic lineage defined by the genus Planctomyces , with 89 and 86% sequence similarity to Planctomyces brasiliensis and Planctomyces maris , respectively. 25724745 8 84 theme C18 1335:1337 arg1 C18 1350:1352 C18 1350:1352 C18 1350:1352 The major fatty acids were C16 : 0 and C16 : 1ω7c; the cells also contained significant amounts of C18 : 1ω7c and C18 : 0. 25724745 8 84 theme C18 1335:1337 arg1 1ω7c 1341:1344 1ω7c 1341:1344 1ω7c 1341:1344 The major fatty acids were C16 : 0 and C16 : 1ω7c; the cells also contained significant amounts of C18 : 1ω7c and C18 : 0. 25724745 8 84 theme C18 1335:1337 arg1 C18 1335:1337 C18 1335:1337 C18 1335:1337 The major fatty acids were C16 : 0 and C16 : 1ω7c; the cells also contained significant amounts of C18 : 1ω7c and C18 : 0. 25724745 8 84 theme C18 1335:1337 arg1 amounts 1324:1330 significant amounts 1312:1330 significant amounts of C18 : 1ω7c and C18 : 0 1312:1356 The major fatty acids were C16 : 0 and C16 : 1ω7c; the cells also contained significant amounts of C18 : 1ω7c and C18 : 0. 25724745 4 85 theme sequence 645:652 arg1 similarity 654:663 89 and 86% sequence similarity 634:663 89 and 86% sequence similarity to Planctomyces brasiliensis and Planctomyces maris , respectively 634:730 16S rRNA gene sequence analysis confirmed that strain P3(T) was a member of the order Planctomycetales and belonged to a phylogenetic lineage defined by the genus Planctomyces , with 89 and 86% sequence similarity to Planctomyces brasiliensis and Planctomyces maris , respectively. 25724745 1 86 theme littoral 79:86 arg1 wetland 88:94 a littoral wetland 77:94 a littoral wetland of a boreal lake 77:111 nov., a stalked planctomycete from a littoral wetland of a boreal lake. 25724745 7 87 theme strain 1143:1148 arg1 T 1153:1153 T 1153:1153 T 1153:1153 Compared with Planctomyces brasiliensis and Planctomyces maris , which require NaCl for growth, strain P3(T) was salt-sensitive and did not develop at NaCl concentrations above 0.5% (w/v). 25724745 7 87 theme strain 1143:1148 arg1 P3 1150:1151 strain P3 1143:1151 strain P3(T) 1143:1154 Compared with Planctomyces brasiliensis and Planctomyces maris , which require NaCl for growth, strain P3(T) was salt-sensitive and did not develop at NaCl concentrations above 0.5% (w/v). 25724745 7 88 dep Planctomyces 1091:1102 arg1 maris 1104:1108 Planctomyces maris 1091:1108 Planctomyces maris 1091:1108 Compared with Planctomyces brasiliensis and Planctomyces maris , which require NaCl for growth, strain P3(T) was salt-sensitive and did not develop at NaCl concentrations above 0.5% (w/v). 25724745 9 89 theme major 1363:1367 arg1 lipids 1382:1387 The major intact polar lipids 1359:1387 The major intact polar lipids 1359:1387 The major intact polar lipids were diacylglycerol-O-(N,N,N-trimethyl)homoserine (DGTS) lipids; the major neutral lipids were long-chain 1,(ω-1)-diols and C31 : 9 hydrocarbon. 25724745 9 89 theme major 1363:1367 arg1 lipids 1446:1451 diacylglycerol-O-(N,N,N-trimethyl)homoserine (DGTS) lipids 1394:1451 diacylglycerol-O-(N,N,N-trimethyl)homoserine (DGTS) lipids 1394:1451 The major intact polar lipids were diacylglycerol-O-(N,N,N-trimethyl)homoserine (DGTS) lipids; the major neutral lipids were long-chain 1,(ω-1)-diols and C31 : 9 hydrocarbon. 25724745 6 90 theme polysaccharides 967:981 arg1 sugars 947:952 Most sugars 942:952 Most sugars 942:952 Most sugars, a number of polysaccharides and several organic acids were the preferred growth substrates. 25724745 6 90 theme polysaccharides 967:981 arg1 number 957:962 a number 955:962 a number of polysaccharides 955:981 Most sugars, a number of polysaccharides and several organic acids were the preferred growth substrates. 25724745 6 90 theme polysaccharides 967:981 arg1 substrates 1035:1044 the preferred growth substrates 1014:1044 the preferred growth substrates 1014:1044 Most sugars, a number of polysaccharides and several organic acids were the preferred growth substrates. 25724745 6 90 theme polysaccharides 967:981 arg1 acids 1003:1007 several organic acids 987:1007 several organic acids 987:1007 Most sugars, a number of polysaccharides and several organic acids were the preferred growth substrates. 25724745 4 91 theme strain 498:503 arg1 member 517:522 a member 515:522 a member of the order Planctomycetales 515:552 16S rRNA gene sequence analysis confirmed that strain P3(T) was a member of the order Planctomycetales and belonged to a phylogenetic lineage defined by the genus Planctomyces , with 89 and 86% sequence similarity to Planctomyces brasiliensis and Planctomyces maris , respectively. 25724745 4 91 theme strain 498:503 arg1 T 508:508 T 508:508 T 508:508 16S rRNA gene sequence analysis confirmed that strain P3(T) was a member of the order Planctomycetales and belonged to a phylogenetic lineage defined by the genus Planctomyces , with 89 and 86% sequence similarity to Planctomyces brasiliensis and Planctomyces maris , respectively. 25724745 4 91 theme strain 498:503 arg1 P3 505:506 strain P3 498:506 strain P3(T) 498:509 16S rRNA gene sequence analysis confirmed that strain P3(T) was a member of the order Planctomycetales and belonged to a phylogenetic lineage defined by the genus Planctomyces , with 89 and 86% sequence similarity to Planctomyces brasiliensis and Planctomyces maris , respectively. 25724745 14 92 theme  =VKM 2016:2020 arg1 T 2029:2029 T 2029:2029 T 2029:2029 The type strain is P3(T) ( =DSM 26348(T) =VKM B-2887(T)). 25724745 14 92 theme  =VKM 2016:2020 arg1 B-2887 2022:2027  =DSM 26348(T) =VKM B-2887 2002:2027  =DSM 26348(T) =VKM B-2887(T) 2002:2030 The type strain is P3(T) ( =DSM 26348(T) =VKM B-2887(T)). 25724745 2 93 theme strain 291:296 arg1 T 301:301 T 301:301 T 301:301 An aerobic, budding, non-pigmented and rosette-forming bacterium was isolated from a littoral wetland of a boreal lake located in Valaam Island, northern Russia, and designated strain P3(T). 25724745 2 93 theme strain 291:296 arg1 P3 298:299 designated strain P3 280:299 designated strain P3(T) 280:302 An aerobic, budding, non-pigmented and rosette-forming bacterium was isolated from a littoral wetland of a boreal lake located in Valaam Island, northern Russia, and designated strain P3(T). 25724745 9 94 theme polar 1376:1380 arg1 lipids 1382:1387 The major intact polar lipids 1359:1387 The major intact polar lipids 1359:1387 The major intact polar lipids were diacylglycerol-O-(N,N,N-trimethyl)homoserine (DGTS) lipids; the major neutral lipids were long-chain 1,(ω-1)-diols and C31 : 9 hydrocarbon. 25724745 9 94 theme polar 1376:1380 arg1 lipids 1446:1451 diacylglycerol-O-(N,N,N-trimethyl)homoserine (DGTS) lipids 1394:1451 diacylglycerol-O-(N,N,N-trimethyl)homoserine (DGTS) lipids 1394:1451 The major intact polar lipids were diacylglycerol-O-(N,N,N-trimethyl)homoserine (DGTS) lipids; the major neutral lipids were long-chain 1,(ω-1)-diols and C31 : 9 hydrocarbon. 25724745 2 95 theme littoral 199:206 arg1 wetland 208:214 a littoral wetland 197:214 a littoral wetland of a boreal lake located in Valaam Island, northern Russia, and designated strain P3(T) 197:302 An aerobic, budding, non-pigmented and rosette-forming bacterium was isolated from a littoral wetland of a boreal lake located in Valaam Island, northern Russia, and designated strain P3(T). 25724745 4 96 theme order 531:535 arg1 Planctomycetales 537:552 the order Planctomycetales 527:552 the order Planctomycetales 527:552 16S rRNA gene sequence analysis confirmed that strain P3(T) was a member of the order Planctomycetales and belonged to a phylogenetic lineage defined by the genus Planctomyces , with 89 and 86% sequence similarity to Planctomyces brasiliensis and Planctomyces maris , respectively. 25724745 5 97 dep acidophilic 759:769 arg1 mesophilic 772:781 mesophilic 772:781 mesophilic 772:781 Strain P3(T) was a mildly acidophilic, mesophilic organism capable of growth at pH values between pH 4.2 and 7.1 (with an optimum at pH 6.0-6.5) and at temperatures between 10 and 30 °C (optimum at 20-28 °C). 25724745 3 98 theme planctomycete 425:437 arg1 morphotype 439:448 a planctomycete morphotype 423:448 a planctomycete morphotype 423:448 Ellipsoidal to pear-shaped cells of this bacterium were covered with crateriform pits and possessed stalks suggesting a planctomycete morphotype. 25724745 11 99 dep Planctomyces 1629:1640 arg1 brasiliensis 1642:1653 Planctomyces brasiliensis 1629:1653 Planctomyces brasiliensis 1629:1653 Strain P3(T) differed from Planctomyces brasiliensis and Planctomyces maris by cell morphology, substrate utilization pattern and a number of physiological characteristics. 25724745 8 100 theme major 1240:1244 arg1 C16 1263:1265 C16 1263:1265 C16 1263:1265 The major fatty acids were C16 : 0 and C16 : 1ω7c; the cells also contained significant amounts of C18 : 1ω7c and C18 : 0. 25724745 8 100 theme major 1240:1244 arg1 acids 1252:1256 The major fatty acids 1236:1256 The major fatty acids 1236:1256 The major fatty acids were C16 : 0 and C16 : 1ω7c; the cells also contained significant amounts of C18 : 1ω7c and C18 : 0. 25724745 12 101 dep sp 1953:1954 arg1 nov. 1947:1950 the name Planctomicrobium piriforme gen. nov. 1906:1950 the name Planctomicrobium piriforme gen. nov. 1906:1950 Based on these data, the novel isolate should be considered as representing a novel genus and species of planctomycetes, for which the name Planctomicrobium piriforme gen. nov., sp. 25249566 15 0 dep MO-SPC2 1742:1748 arg1 23952 1776:1780  = JCM 17281(T) = DSM 23952 1754:1780  = JCM 17281(T) = DSM 23952(T) 1754:1783 The type strain is MO-SPC2(T) ( = JCM 17281(T) = DSM 23952(T)). 25249566 15 0 dep MO-SPC2 1742:1748 arg1 T 1782:1782 T 1782:1782 T 1782:1782 The type strain is MO-SPC2(T) ( = JCM 17281(T) = DSM 23952(T)). 25249566 2 1 dep anaerobic 165:173 arg1 psychrophilic 176:188 psychrophilic 176:188 psychrophilic 176:188 An anaerobic, psychrophilic bacterium, strain MO-SPC2(T), was isolated from a methanogenic microbial community in a continuous-flow bioreactor that was established from subseafloor sediments collected from off the Shimokita Peninsula of Japan in the north-western Pacific Ocean. 25249566 9 2 theme major 1033:1037 arg1 C14  1065:1068 C14  1065:1068 C14  1065:1068 The major cellular fatty acids were C14 : 0, C16 : 0 and C16 : 1ω9. 25249566 9 2 theme major 1033:1037 arg1 acids 1054:1058 The major cellular fatty acids 1029:1058 The major cellular fatty acids 1029:1058 The major cellular fatty acids were C14 : 0, C16 : 0 and C16 : 1ω9. 25249566 12 3 theme phylogenetic 1198:1209 arg1 analysis 1211:1218 16S rRNA gene-based phylogenetic analysis 1178:1218 16S rRNA gene-based phylogenetic analysis 1178:1218 16S rRNA gene-based phylogenetic analysis showed that strain MO-SPC2(T) was affiliated with the genus Sphaerochaeta within the phylum Spirochaetes, and its closest relatives were Sphaerochaeta pleomorpha Grapes(T) (88.4 % sequence identity), Sphaerochaeta globosa Buddy(T) (86.7 %) and Sphaerochaeta coccoides SPN1(T) (85.4 %). 25249566 9 4 theme fatty 1048:1052 arg1 C14  1065:1068 C14  1065:1068 C14  1065:1068 The major cellular fatty acids were C14 : 0, C16 : 0 and C16 : 1ω9. 25249566 9 4 theme fatty 1048:1052 arg1 acids 1054:1058 The major cellular fatty acids 1029:1058 The major cellular fatty acids 1029:1058 The major cellular fatty acids were C14 : 0, C16 : 0 and C16 : 1ω9. 25249566 13 5 theme phenotypic 1515:1524 arg1 characteristics 1526:1540 phenotypic characteristics 1515:1540 phenotypic characteristics 1515:1540 Based on phenotypic characteristics and phylogenetic traits, strain MO-SPC2(T) is considered to represent a novel species of the genus Sphaerochaeta, for which the name Sphaerochaeta multiformis sp. 25249566 13 6 theme Sphaerochaeta 1641:1653 arg1 species 1620:1626 a novel species 1612:1626 a novel species 1612:1626 Based on phenotypic characteristics and phylogenetic traits, strain MO-SPC2(T) is considered to represent a novel species of the genus Sphaerochaeta, for which the name Sphaerochaeta multiformis sp. 25249566 2 7 theme methanogenic 240:251 arg1 community 263:271 a methanogenic microbial community 238:271 a methanogenic microbial community in a continuous-flow bioreactor that was established from subseafloor sediments collected from off the Shimokita Peninsula of Japan in the north-western Pacific Ocean 238:438 An anaerobic, psychrophilic bacterium, strain MO-SPC2(T), was isolated from a methanogenic microbial community in a continuous-flow bioreactor that was established from subseafloor sediments collected from off the Shimokita Peninsula of Japan in the north-western Pacific Ocean. 25249566 12 8 theme rRNA 1182:1185 arg1 analysis 1211:1218 16S rRNA gene-based phylogenetic analysis 1178:1218 16S rRNA gene-based phylogenetic analysis 1178:1218 16S rRNA gene-based phylogenetic analysis showed that strain MO-SPC2(T) was affiliated with the genus Sphaerochaeta within the phylum Spirochaetes, and its closest relatives were Sphaerochaeta pleomorpha Grapes(T) (88.4 % sequence identity), Sphaerochaeta globosa Buddy(T) (86.7 %) and Sphaerochaeta coccoides SPN1(T) (85.4 %). 25249566 1 9 attach isolated 74:81 arg1 sediment 100:107 subseafloor sediment 88:107 subseafloor sediment 88:107 nov., an anaerobic, psychrophilic bacterium isolated from subseafloor sediment, and emended description of the genus Sphaerochaeta. 25249566 1 9 attach isolated 74:81 arg2 bacterium 64:72 an anaerobic, psychrophilic bacterium 36:72 an anaerobic, psychrophilic bacterium isolated from subseafloor sediment 36:107 nov., an anaerobic, psychrophilic bacterium isolated from subseafloor sediment, and emended description of the genus Sphaerochaeta. 25249566 12 10 theme % 1398:1398 arg1 identity 1409:1416 88.4 % sequence identity 1393:1416 88.4 % sequence identity 1393:1416 16S rRNA gene-based phylogenetic analysis showed that strain MO-SPC2(T) was affiliated with the genus Sphaerochaeta within the phylum Spirochaetes, and its closest relatives were Sphaerochaeta pleomorpha Grapes(T) (88.4 % sequence identity), Sphaerochaeta globosa Buddy(T) (86.7 %) and Sphaerochaeta coccoides SPN1(T) (85.4 %). 25249566 12 10 theme % 1398:1398 arg1 Grapes 1382:1387 Sphaerochaeta pleomorpha Grapes 1357:1387 Sphaerochaeta pleomorpha Grapes(T) (88.4 % sequence identity) 1357:1417 16S rRNA gene-based phylogenetic analysis showed that strain MO-SPC2(T) was affiliated with the genus Sphaerochaeta within the phylum Spirochaetes, and its closest relatives were Sphaerochaeta pleomorpha Grapes(T) (88.4 % sequence identity), Sphaerochaeta globosa Buddy(T) (86.7 %) and Sphaerochaeta coccoides SPN1(T) (85.4 %). 25249566 16 11 theme emended 1790:1796 arg1 description 1798:1808 An emended description 1787:1808 An emended description of the genus Sphaerochaeta 1787:1835 An emended description of the genus Sphaerochaeta is also proposed. 25249566 5 12 theme NaCl 732:735 arg1 l 706:706 20-40 g NaCl l 693:706 20-40 g NaCl l(-1) (optimally at 20-30 NaCl l(-1)) 693:742 Strain MO-SPC2(T) grew at 0-17 °C (optimally at 9 °C), at pH 6.0-8.0 (optimally at pH 6.8-7.2) and in 20-40 g NaCl l(-1) (optimally at 20-30 NaCl l(-1)). 25249566 5 12 theme NaCl 732:735 arg1 l 737:737 optimally at 20-30 NaCl l(-1) 713:741 optimally at 20-30 NaCl l(-1) 713:741 Strain MO-SPC2(T) grew at 0-17 °C (optimally at 9 °C), at pH 6.0-8.0 (optimally at pH 6.8-7.2) and in 20-40 g NaCl l(-1) (optimally at 20-30 NaCl l(-1)). 25249566 7 13 theme carbon 905:910 arg1 dioxide 912:918 carbon dioxide 905:918 carbon dioxide 905:918 The major end products of glucose fermentation were acetate, ethanol, hydrogen and carbon dioxide. 25249566 1 14 theme emended 114:120 arg1 description 122:132 emended description 114:132 emended description of the genus Sphaerochaeta 114:159 nov., an anaerobic, psychrophilic bacterium isolated from subseafloor sediment, and emended description of the genus Sphaerochaeta. 25249566 13 15 theme name 1670:1673 arg1 sp 1701:1702 the name Sphaerochaeta multiformis sp 1666:1702 the name Sphaerochaeta multiformis sp 1666:1702 Based on phenotypic characteristics and phylogenetic traits, strain MO-SPC2(T) is considered to represent a novel species of the genus Sphaerochaeta, for which the name Sphaerochaeta multiformis sp. 25249566 7 16 theme glucose 848:854 arg1 fermentation 856:867 glucose fermentation 848:867 glucose fermentation 848:867 The major end products of glucose fermentation were acetate, ethanol, hydrogen and carbon dioxide. 25249566 12 17 theme coccoides 1478:1486 arg1 T 1493:1493 T 1493:1493 T 1493:1493 16S rRNA gene-based phylogenetic analysis showed that strain MO-SPC2(T) was affiliated with the genus Sphaerochaeta within the phylum Spirochaetes, and its closest relatives were Sphaerochaeta pleomorpha Grapes(T) (88.4 % sequence identity), Sphaerochaeta globosa Buddy(T) (86.7 %) and Sphaerochaeta coccoides SPN1(T) (85.4 %). 25249566 12 17 theme coccoides 1478:1486 arg1 SPN1 1488:1491 Sphaerochaeta coccoides SPN1 1464:1491 Sphaerochaeta coccoides SPN1(T) (85.4 %) 1464:1503 16S rRNA gene-based phylogenetic analysis showed that strain MO-SPC2(T) was affiliated with the genus Sphaerochaeta within the phylum Spirochaetes, and its closest relatives were Sphaerochaeta pleomorpha Grapes(T) (88.4 % sequence identity), Sphaerochaeta globosa Buddy(T) (86.7 %) and Sphaerochaeta coccoides SPN1(T) (85.4 %). 25249566 12 17 theme coccoides 1478:1486 arg1 % 1502:1502 85.4 % 1497:1502 85.4 % 1497:1502 16S rRNA gene-based phylogenetic analysis showed that strain MO-SPC2(T) was affiliated with the genus Sphaerochaeta within the phylum Spirochaetes, and its closest relatives were Sphaerochaeta pleomorpha Grapes(T) (88.4 % sequence identity), Sphaerochaeta globosa Buddy(T) (86.7 %) and Sphaerochaeta coccoides SPN1(T) (85.4 %). 25249566 13 18 theme genus 1635:1639 arg1 Sphaerochaeta 1641:1653 the genus Sphaerochaeta 1631:1653 the genus Sphaerochaeta 1631:1653 Based on phenotypic characteristics and phylogenetic traits, strain MO-SPC2(T) is considered to represent a novel species of the genus Sphaerochaeta, for which the name Sphaerochaeta multiformis sp. 25249566 1 19 theme genus 141:145 arg1 Sphaerochaeta 147:159 the genus Sphaerochaeta 137:159 the genus Sphaerochaeta 137:159 nov., an anaerobic, psychrophilic bacterium isolated from subseafloor sediment, and emended description of the genus Sphaerochaeta. 25249566 12 20 theme Sphaerochaeta 1357:1369 arg1 T 1389:1389 T 1389:1389 T 1389:1389 16S rRNA gene-based phylogenetic analysis showed that strain MO-SPC2(T) was affiliated with the genus Sphaerochaeta within the phylum Spirochaetes, and its closest relatives were Sphaerochaeta pleomorpha Grapes(T) (88.4 % sequence identity), Sphaerochaeta globosa Buddy(T) (86.7 %) and Sphaerochaeta coccoides SPN1(T) (85.4 %). 25249566 12 20 theme Sphaerochaeta 1357:1369 arg1 Grapes 1382:1387 Sphaerochaeta pleomorpha Grapes 1357:1387 Sphaerochaeta pleomorpha Grapes(T) (88.4 % sequence identity) 1357:1417 16S rRNA gene-based phylogenetic analysis showed that strain MO-SPC2(T) was affiliated with the genus Sphaerochaeta within the phylum Spirochaetes, and its closest relatives were Sphaerochaeta pleomorpha Grapes(T) (88.4 % sequence identity), Sphaerochaeta globosa Buddy(T) (86.7 %) and Sphaerochaeta coccoides SPN1(T) (85.4 %). 25249566 12 20 theme Sphaerochaeta 1357:1369 arg1 identity 1409:1416 88.4 % sequence identity 1393:1416 88.4 % sequence identity 1393:1416 16S rRNA gene-based phylogenetic analysis showed that strain MO-SPC2(T) was affiliated with the genus Sphaerochaeta within the phylum Spirochaetes, and its closest relatives were Sphaerochaeta pleomorpha Grapes(T) (88.4 % sequence identity), Sphaerochaeta globosa Buddy(T) (86.7 %) and Sphaerochaeta coccoides SPN1(T) (85.4 %). 25249566 7 21 theme major 826:830 arg1 acetate 874:880 acetate 874:880 acetate 874:880 The major end products of glucose fermentation were acetate, ethanol, hydrogen and carbon dioxide. 25249566 7 21 theme major 826:830 arg1 products 836:843 The major end products 822:843 The major end products of glucose fermentation 822:867 The major end products of glucose fermentation were acetate, ethanol, hydrogen and carbon dioxide. 25249566 13 22 theme Sphaerochaeta 1675:1687 arg1 sp 1701:1702 the name Sphaerochaeta multiformis sp 1666:1702 the name Sphaerochaeta multiformis sp 1666:1702 Based on phenotypic characteristics and phylogenetic traits, strain MO-SPC2(T) is considered to represent a novel species of the genus Sphaerochaeta, for which the name Sphaerochaeta multiformis sp. 25249566 13 23 theme novel 1614:1618 arg1 species 1620:1626 a novel species 1612:1626 a novel species 1612:1626 Based on phenotypic characteristics and phylogenetic traits, strain MO-SPC2(T) is considered to represent a novel species of the genus Sphaerochaeta, for which the name Sphaerochaeta multiformis sp. 25249566 15 24 theme  = JCM 1754:1759 arg1 23952 1776:1780  = JCM 17281(T) = DSM 23952 1754:1780  = JCM 17281(T) = DSM 23952(T) 1754:1783 The type strain is MO-SPC2(T) ( = JCM 17281(T) = DSM 23952(T)). 25249566 15 24 theme  = JCM 1754:1759 arg1 T 1782:1782 T 1782:1782 T 1782:1782 The type strain is MO-SPC2(T) ( = JCM 17281(T) = DSM 23952(T)). 25249566 2 25 theme Shimokita 376:384 arg1 Peninsula 386:394 off the Shimokita Peninsula 368:394 off the Shimokita Peninsula of Japan in the north-western Pacific Ocean 368:438 An anaerobic, psychrophilic bacterium, strain MO-SPC2(T), was isolated from a methanogenic microbial community in a continuous-flow bioreactor that was established from subseafloor sediments collected from off the Shimokita Peninsula of Japan in the north-western Pacific Ocean. 25249566 0 26 theme Sphaerochaeta 0:12 arg1 sp 26:27 Sphaerochaeta multiformis sp 0:27 Sphaerochaeta multiformis sp. 0:28 Sphaerochaeta multiformis sp. 25249566 1 27 theme subseafloor 88:98 arg1 sediment 100:107 subseafloor sediment 88:107 subseafloor sediment 88:107 nov., an anaerobic, psychrophilic bacterium isolated from subseafloor sediment, and emended description of the genus Sphaerochaeta. 25249566 13 28 theme strain 1567:1572 arg1 MO-SPC2 1574:1580 strain MO-SPC2 1567:1580 strain MO-SPC2(T) 1567:1583 Based on phenotypic characteristics and phylogenetic traits, strain MO-SPC2(T) is considered to represent a novel species of the genus Sphaerochaeta, for which the name Sphaerochaeta multiformis sp. 25249566 13 28 theme strain 1567:1572 arg1 T 1582:1582 T 1582:1582 T 1582:1582 Based on phenotypic characteristics and phylogenetic traits, strain MO-SPC2(T) is considered to represent a novel species of the genus Sphaerochaeta, for which the name Sphaerochaeta multiformis sp. 25249566 2 29 theme north-western 412:424 arg1 Ocean 434:438 the north-western Pacific Ocean 408:438 the north-western Pacific Ocean 408:438 An anaerobic, psychrophilic bacterium, strain MO-SPC2(T), was isolated from a methanogenic microbial community in a continuous-flow bioreactor that was established from subseafloor sediments collected from off the Shimokita Peninsula of Japan in the north-western Pacific Ocean. 25249566 8 30 theme polar 934:938 arg1 lipids 940:945 The abundant polar lipids 921:945 The abundant polar lipids of strain MO-SPC2(T) 921:966 The abundant polar lipids of strain MO-SPC2(T) were phosphatidylglycolipids, phospholipids and glycolipids. 25249566 8 30 theme polar 934:938 arg1 phosphatidylglycolipids 973:995 phosphatidylglycolipids 973:995 phosphatidylglycolipids 973:995 The abundant polar lipids of strain MO-SPC2(T) were phosphatidylglycolipids, phospholipids and glycolipids. 25249566 12 31 theme Sphaerochaeta 1420:1432 arg1 Buddy 1442:1446 Sphaerochaeta globosa Buddy 1420:1446 Sphaerochaeta globosa Buddy(T) (86.7 %) 1420:1458 16S rRNA gene-based phylogenetic analysis showed that strain MO-SPC2(T) was affiliated with the genus Sphaerochaeta within the phylum Spirochaetes, and its closest relatives were Sphaerochaeta pleomorpha Grapes(T) (88.4 % sequence identity), Sphaerochaeta globosa Buddy(T) (86.7 %) and Sphaerochaeta coccoides SPN1(T) (85.4 %). 25249566 12 31 theme Sphaerochaeta 1420:1432 arg1 % 1457:1457 86.7 % 1452:1457 86.7 % 1452:1457 16S rRNA gene-based phylogenetic analysis showed that strain MO-SPC2(T) was affiliated with the genus Sphaerochaeta within the phylum Spirochaetes, and its closest relatives were Sphaerochaeta pleomorpha Grapes(T) (88.4 % sequence identity), Sphaerochaeta globosa Buddy(T) (86.7 %) and Sphaerochaeta coccoides SPN1(T) (85.4 %). 25249566 12 31 theme Sphaerochaeta 1420:1432 arg1 T 1448:1448 T 1448:1448 T 1448:1448 16S rRNA gene-based phylogenetic analysis showed that strain MO-SPC2(T) was affiliated with the genus Sphaerochaeta within the phylum Spirochaetes, and its closest relatives were Sphaerochaeta pleomorpha Grapes(T) (88.4 % sequence identity), Sphaerochaeta globosa Buddy(T) (86.7 %) and Sphaerochaeta coccoides SPN1(T) (85.4 %). 25249566 2 32 from community 263:271 arg1 bioreactor 294:303 a continuous-flow bioreactor 276:303 a continuous-flow bioreactor that was established from subseafloor sediments collected from off the Shimokita Peninsula of Japan in the north-western Pacific Ocean 276:438 An anaerobic, psychrophilic bacterium, strain MO-SPC2(T), was isolated from a methanogenic microbial community in a continuous-flow bioreactor that was established from subseafloor sediments collected from off the Shimokita Peninsula of Japan in the north-western Pacific Ocean. 25249566 5 33 theme g 699:699 arg1 -1 708:709 -1 708:709 -1 708:709 Strain MO-SPC2(T) grew at 0-17 °C (optimally at 9 °C), at pH 6.0-8.0 (optimally at pH 6.8-7.2) and in 20-40 g NaCl l(-1) (optimally at 20-30 NaCl l(-1)). 25249566 5 33 theme g 699:699 arg1 l 706:706 20-40 g NaCl l 693:706 20-40 g NaCl l(-1) (optimally at 20-30 NaCl l(-1)) 693:742 Strain MO-SPC2(T) grew at 0-17 °C (optimally at 9 °C), at pH 6.0-8.0 (optimally at pH 6.8-7.2) and in 20-40 g NaCl l(-1) (optimally at 20-30 NaCl l(-1)). 25249566 5 33 theme g 699:699 arg1 l 737:737 optimally at 20-30 NaCl l(-1) 713:741 optimally at 20-30 NaCl l(-1) 713:741 Strain MO-SPC2(T) grew at 0-17 °C (optimally at 9 °C), at pH 6.0-8.0 (optimally at pH 6.8-7.2) and in 20-40 g NaCl l(-1) (optimally at 20-30 NaCl l(-1)). 25249566 2 34 theme subseafloor 331:341 arg1 sediments 343:351 subseafloor sediments 331:351 subseafloor sediments collected from off the Shimokita Peninsula of Japan in the north-western Pacific Ocean 331:438 An anaerobic, psychrophilic bacterium, strain MO-SPC2(T), was isolated from a methanogenic microbial community in a continuous-flow bioreactor that was established from subseafloor sediments collected from off the Shimokita Peninsula of Japan in the north-western Pacific Ocean. 25249566 8 35 theme MO-SPC2 957:963 arg1 lipids 940:945 The abundant polar lipids 921:945 The abundant polar lipids of strain MO-SPC2(T) 921:966 The abundant polar lipids of strain MO-SPC2(T) were phosphatidylglycolipids, phospholipids and glycolipids. 25249566 8 35 theme MO-SPC2 957:963 arg1 phosphatidylglycolipids 973:995 phosphatidylglycolipids 973:995 phosphatidylglycolipids 973:995 The abundant polar lipids of strain MO-SPC2(T) were phosphatidylglycolipids, phospholipids and glycolipids. 25249566 2 36 theme strain 201:206 arg1 T 216:216 T 216:216 T 216:216 An anaerobic, psychrophilic bacterium, strain MO-SPC2(T), was isolated from a methanogenic microbial community in a continuous-flow bioreactor that was established from subseafloor sediments collected from off the Shimokita Peninsula of Japan in the north-western Pacific Ocean. 25249566 2 36 theme strain 201:206 arg1 bacterium 190:198 An anaerobic, psychrophilic bacterium 162:198 An anaerobic, psychrophilic bacterium 162:198 An anaerobic, psychrophilic bacterium, strain MO-SPC2(T), was isolated from a methanogenic microbial community in a continuous-flow bioreactor that was established from subseafloor sediments collected from off the Shimokita Peninsula of Japan in the north-western Pacific Ocean. 25249566 2 36 theme strain 201:206 arg1 MO-SPC2 208:214 strain MO-SPC2 201:214 strain MO-SPC2(T) 201:217 An anaerobic, psychrophilic bacterium, strain MO-SPC2(T), was isolated from a methanogenic microbial community in a continuous-flow bioreactor that was established from subseafloor sediments collected from off the Shimokita Peninsula of Japan in the north-western Pacific Ocean. 25249566 3 37 theme cell 517:520 arg1 morphologies 522:533 spherical, annular, curved rod, helical and coccoid cell morphologies 465:533 spherical, annular, curved rod, helical and coccoid cell morphologies 465:533 Cells were pleomorphic: spherical, annular, curved rod, helical and coccoid cell morphologies were observed. 25249566 16 38 theme Sphaerochaeta 1823:1835 arg1 description 1798:1808 An emended description 1787:1808 An emended description of the genus Sphaerochaeta 1787:1835 An emended description of the genus Sphaerochaeta is also proposed. 25249566 3 39 theme helical 497:503 arg1 morphologies 522:533 spherical, annular, curved rod, helical and coccoid cell morphologies 465:533 spherical, annular, curved rod, helical and coccoid cell morphologies 465:533 Cells were pleomorphic: spherical, annular, curved rod, helical and coccoid cell morphologies were observed. 25249566 3 40 dep spherical 465:473 arg1 curved 485:490 curved 485:490 curved 485:490 Cells were pleomorphic: spherical, annular, curved rod, helical and coccoid cell morphologies were observed. 25249566 3 40 dep spherical 465:473 arg1 annular 476:482 annular 476:482 annular 476:482 Cells were pleomorphic: spherical, annular, curved rod, helical and coccoid cell morphologies were observed. 25249566 13 41 theme phylogenetic 1546:1557 arg1 traits 1559:1564 phylogenetic traits 1546:1564 phylogenetic traits 1546:1564 Based on phenotypic characteristics and phylogenetic traits, strain MO-SPC2(T) is considered to represent a novel species of the genus Sphaerochaeta, for which the name Sphaerochaeta multiformis sp. 25249566 3 42 theme rod 492:494 arg1 morphologies 522:533 spherical, annular, curved rod, helical and coccoid cell morphologies 465:533 spherical, annular, curved rod, helical and coccoid cell morphologies 465:533 Cells were pleomorphic: spherical, annular, curved rod, helical and coccoid cell morphologies were observed. 25249566 9 43 theme cellular 1039:1046 arg1 C14  1065:1068 C14  1065:1068 C14  1065:1068 The major cellular fatty acids were C14 : 0, C16 : 0 and C16 : 1ω9. 25249566 9 43 theme cellular 1039:1046 arg1 acids 1054:1058 The major cellular fatty acids 1029:1058 The major cellular fatty acids 1029:1058 The major cellular fatty acids were C14 : 0, C16 : 0 and C16 : 1ω9. 25249566 12 44 theme strain 1232:1237 arg1 MO-SPC2 1239:1245 strain MO-SPC2 1232:1245 strain MO-SPC2(T) 1232:1248 16S rRNA gene-based phylogenetic analysis showed that strain MO-SPC2(T) was affiliated with the genus Sphaerochaeta within the phylum Spirochaetes, and its closest relatives were Sphaerochaeta pleomorpha Grapes(T) (88.4 % sequence identity), Sphaerochaeta globosa Buddy(T) (86.7 %) and Sphaerochaeta coccoides SPN1(T) (85.4 %). 25249566 12 44 theme strain 1232:1237 arg1 T 1247:1247 T 1247:1247 T 1247:1247 16S rRNA gene-based phylogenetic analysis showed that strain MO-SPC2(T) was affiliated with the genus Sphaerochaeta within the phylum Spirochaetes, and its closest relatives were Sphaerochaeta pleomorpha Grapes(T) (88.4 % sequence identity), Sphaerochaeta globosa Buddy(T) (86.7 %) and Sphaerochaeta coccoides SPN1(T) (85.4 %). 25249566 12 45 theme gene-based 1187:1196 arg1 analysis 1211:1218 16S rRNA gene-based phylogenetic analysis 1178:1218 16S rRNA gene-based phylogenetic analysis 1178:1218 16S rRNA gene-based phylogenetic analysis showed that strain MO-SPC2(T) was affiliated with the genus Sphaerochaeta within the phylum Spirochaetes, and its closest relatives were Sphaerochaeta pleomorpha Grapes(T) (88.4 % sequence identity), Sphaerochaeta globosa Buddy(T) (86.7 %) and Sphaerochaeta coccoides SPN1(T) (85.4 %). 25249566 4 46 theme helical 576:582 arg1 cells 584:588 helical cells 576:588 helical cells 576:588 Motility only occurred in helical cells. 25249566 13 47 theme multiformis 1689:1699 arg1 sp 1701:1702 the name Sphaerochaeta multiformis sp 1666:1702 the name Sphaerochaeta multiformis sp 1666:1702 Based on phenotypic characteristics and phylogenetic traits, strain MO-SPC2(T) is considered to represent a novel species of the genus Sphaerochaeta, for which the name Sphaerochaeta multiformis sp. 25249566 2 48 theme microbial 253:261 arg1 community 263:271 a methanogenic microbial community 238:271 a methanogenic microbial community in a continuous-flow bioreactor that was established from subseafloor sediments collected from off the Shimokita Peninsula of Japan in the north-western Pacific Ocean 238:438 An anaerobic, psychrophilic bacterium, strain MO-SPC2(T), was isolated from a methanogenic microbial community in a continuous-flow bioreactor that was established from subseafloor sediments collected from off the Shimokita Peninsula of Japan in the north-western Pacific Ocean. 25249566 12 49 theme 88.4  1393:1397 arg1 identity 1409:1416 88.4 % sequence identity 1393:1416 88.4 % sequence identity 1393:1416 16S rRNA gene-based phylogenetic analysis showed that strain MO-SPC2(T) was affiliated with the genus Sphaerochaeta within the phylum Spirochaetes, and its closest relatives were Sphaerochaeta pleomorpha Grapes(T) (88.4 % sequence identity), Sphaerochaeta globosa Buddy(T) (86.7 %) and Sphaerochaeta coccoides SPN1(T) (85.4 %). 25249566 12 49 theme 88.4  1393:1397 arg1 Grapes 1382:1387 Sphaerochaeta pleomorpha Grapes 1357:1387 Sphaerochaeta pleomorpha Grapes(T) (88.4 % sequence identity) 1357:1417 16S rRNA gene-based phylogenetic analysis showed that strain MO-SPC2(T) was affiliated with the genus Sphaerochaeta within the phylum Spirochaetes, and its closest relatives were Sphaerochaeta pleomorpha Grapes(T) (88.4 % sequence identity), Sphaerochaeta globosa Buddy(T) (86.7 %) and Sphaerochaeta coccoides SPN1(T) (85.4 %). 25249566 11 50 theme G+C 1140:1142 arg1 % 1175:1175 32.3 mol% 1167:1175 32.3 mol% 1167:1175 The G+C content of the DNA was 32.3 mol%. 25249566 11 50 theme G+C 1140:1142 arg1 content 1144:1150 The G+C content 1136:1150 The G+C content of the DNA 1136:1161 The G+C content of the DNA was 32.3 mol%. 25249566 2 51 theme continuous-flow 278:292 arg1 bioreactor 294:303 a continuous-flow bioreactor 276:303 a continuous-flow bioreactor that was established from subseafloor sediments collected from off the Shimokita Peninsula of Japan in the north-western Pacific Ocean 276:438 An anaerobic, psychrophilic bacterium, strain MO-SPC2(T), was isolated from a methanogenic microbial community in a continuous-flow bioreactor that was established from subseafloor sediments collected from off the Shimokita Peninsula of Japan in the north-western Pacific Ocean. 25249566 12 52 theme sequence 1400:1407 arg1 identity 1409:1416 88.4 % sequence identity 1393:1416 88.4 % sequence identity 1393:1416 16S rRNA gene-based phylogenetic analysis showed that strain MO-SPC2(T) was affiliated with the genus Sphaerochaeta within the phylum Spirochaetes, and its closest relatives were Sphaerochaeta pleomorpha Grapes(T) (88.4 % sequence identity), Sphaerochaeta globosa Buddy(T) (86.7 %) and Sphaerochaeta coccoides SPN1(T) (85.4 %). 25249566 12 52 theme sequence 1400:1407 arg1 Grapes 1382:1387 Sphaerochaeta pleomorpha Grapes 1357:1387 Sphaerochaeta pleomorpha Grapes(T) (88.4 % sequence identity) 1357:1417 16S rRNA gene-based phylogenetic analysis showed that strain MO-SPC2(T) was affiliated with the genus Sphaerochaeta within the phylum Spirochaetes, and its closest relatives were Sphaerochaeta pleomorpha Grapes(T) (88.4 % sequence identity), Sphaerochaeta globosa Buddy(T) (86.7 %) and Sphaerochaeta coccoides SPN1(T) (85.4 %). 25249566 12 53 theme 16S 1178:1180 arg1 rRNA 1182:1185 16S rRNA 1178:1185 16S rRNA gene-based phylogenetic analysis 1178:1218 16S rRNA gene-based phylogenetic analysis showed that strain MO-SPC2(T) was affiliated with the genus Sphaerochaeta within the phylum Spirochaetes, and its closest relatives were Sphaerochaeta pleomorpha Grapes(T) (88.4 % sequence identity), Sphaerochaeta globosa Buddy(T) (86.7 %) and Sphaerochaeta coccoides SPN1(T) (85.4 %). 25249566 1 54 dep anaerobic 39:47 arg1 psychrophilic 50:62 psychrophilic 50:62 psychrophilic 50:62 nov., an anaerobic, psychrophilic bacterium isolated from subseafloor sediment, and emended description of the genus Sphaerochaeta. 25249566 5 55 from pH 674:675 arg1 pH 649:650 pH 6.0-8.0 649:658 pH 6.0-8.0 (optimally at pH 6.8-7.2) 649:684 Strain MO-SPC2(T) grew at 0-17 °C (optimally at 9 °C), at pH 6.0-8.0 (optimally at pH 6.8-7.2) and in 20-40 g NaCl l(-1) (optimally at 20-30 NaCl l(-1)). 25249566 2 56 attach isolated 224:231 arg1 community 263:271 a methanogenic microbial community 238:271 a methanogenic microbial community in a continuous-flow bioreactor that was established from subseafloor sediments collected from off the Shimokita Peninsula of Japan in the north-western Pacific Ocean 238:438 An anaerobic, psychrophilic bacterium, strain MO-SPC2(T), was isolated from a methanogenic microbial community in a continuous-flow bioreactor that was established from subseafloor sediments collected from off the Shimokita Peninsula of Japan in the north-western Pacific Ocean. 25249566 2 56 attach isolated 224:231 arg2 MO-SPC2 208:214 strain MO-SPC2 201:214 strain MO-SPC2(T) 201:217 An anaerobic, psychrophilic bacterium, strain MO-SPC2(T), was isolated from a methanogenic microbial community in a continuous-flow bioreactor that was established from subseafloor sediments collected from off the Shimokita Peninsula of Japan in the north-western Pacific Ocean. 25249566 2 56 attach isolated 224:231 arg2 bacterium 190:198 An anaerobic, psychrophilic bacterium 162:198 An anaerobic, psychrophilic bacterium 162:198 An anaerobic, psychrophilic bacterium, strain MO-SPC2(T), was isolated from a methanogenic microbial community in a continuous-flow bioreactor that was established from subseafloor sediments collected from off the Shimokita Peninsula of Japan in the north-western Pacific Ocean. 25249566 11 57 theme DNA 1159:1161 arg1 % 1175:1175 32.3 mol% 1167:1175 32.3 mol% 1167:1175 The G+C content of the DNA was 32.3 mol%. 25249566 11 57 theme DNA 1159:1161 arg1 content 1144:1150 The G+C content 1136:1150 The G+C content of the DNA 1136:1161 The G+C content of the DNA was 32.3 mol%. 25249566 5 58 dep pH 674:675 arg1 optimally 661:669 optimally 661:669 optimally 661:669 Strain MO-SPC2(T) grew at 0-17 °C (optimally at 9 °C), at pH 6.0-8.0 (optimally at pH 6.8-7.2) and in 20-40 g NaCl l(-1) (optimally at 20-30 NaCl l(-1)). 25249566 5 59 theme Strain 591:596 arg1 T 606:606 T 606:606 T 606:606 Strain MO-SPC2(T) grew at 0-17 °C (optimally at 9 °C), at pH 6.0-8.0 (optimally at pH 6.8-7.2) and in 20-40 g NaCl l(-1) (optimally at 20-30 NaCl l(-1)). 25249566 5 59 theme Strain 591:596 arg1 MO-SPC2 598:604 Strain MO-SPC2 591:604 Strain MO-SPC2(T) 591:607 Strain MO-SPC2(T) grew at 0-17 °C (optimally at 9 °C), at pH 6.0-8.0 (optimally at pH 6.8-7.2) and in 20-40 g NaCl l(-1) (optimally at 20-30 NaCl l(-1)). 25249566 7 60 theme fermentation 856:867 arg1 acetate 874:880 acetate 874:880 acetate 874:880 The major end products of glucose fermentation were acetate, ethanol, hydrogen and carbon dioxide. 25249566 7 60 theme fermentation 856:867 arg1 products 836:843 The major end products 822:843 The major end products of glucose fermentation 822:867 The major end products of glucose fermentation were acetate, ethanol, hydrogen and carbon dioxide. 25249566 12 61 theme Sphaerochaeta 1464:1476 arg1 T 1493:1493 T 1493:1493 T 1493:1493 16S rRNA gene-based phylogenetic analysis showed that strain MO-SPC2(T) was affiliated with the genus Sphaerochaeta within the phylum Spirochaetes, and its closest relatives were Sphaerochaeta pleomorpha Grapes(T) (88.4 % sequence identity), Sphaerochaeta globosa Buddy(T) (86.7 %) and Sphaerochaeta coccoides SPN1(T) (85.4 %). 25249566 12 61 theme Sphaerochaeta 1464:1476 arg1 SPN1 1488:1491 Sphaerochaeta coccoides SPN1 1464:1491 Sphaerochaeta coccoides SPN1(T) (85.4 %) 1464:1503 16S rRNA gene-based phylogenetic analysis showed that strain MO-SPC2(T) was affiliated with the genus Sphaerochaeta within the phylum Spirochaetes, and its closest relatives were Sphaerochaeta pleomorpha Grapes(T) (88.4 % sequence identity), Sphaerochaeta globosa Buddy(T) (86.7 %) and Sphaerochaeta coccoides SPN1(T) (85.4 %). 25249566 12 61 theme Sphaerochaeta 1464:1476 arg1 % 1502:1502 85.4 % 1497:1502 85.4 % 1497:1502 16S rRNA gene-based phylogenetic analysis showed that strain MO-SPC2(T) was affiliated with the genus Sphaerochaeta within the phylum Spirochaetes, and its closest relatives were Sphaerochaeta pleomorpha Grapes(T) (88.4 % sequence identity), Sphaerochaeta globosa Buddy(T) (86.7 %) and Sphaerochaeta coccoides SPN1(T) (85.4 %). 25249566 12 62 theme pleomorpha 1371:1380 arg1 T 1389:1389 T 1389:1389 T 1389:1389 16S rRNA gene-based phylogenetic analysis showed that strain MO-SPC2(T) was affiliated with the genus Sphaerochaeta within the phylum Spirochaetes, and its closest relatives were Sphaerochaeta pleomorpha Grapes(T) (88.4 % sequence identity), Sphaerochaeta globosa Buddy(T) (86.7 %) and Sphaerochaeta coccoides SPN1(T) (85.4 %). 25249566 12 62 theme pleomorpha 1371:1380 arg1 Grapes 1382:1387 Sphaerochaeta pleomorpha Grapes 1357:1387 Sphaerochaeta pleomorpha Grapes(T) (88.4 % sequence identity) 1357:1417 16S rRNA gene-based phylogenetic analysis showed that strain MO-SPC2(T) was affiliated with the genus Sphaerochaeta within the phylum Spirochaetes, and its closest relatives were Sphaerochaeta pleomorpha Grapes(T) (88.4 % sequence identity), Sphaerochaeta globosa Buddy(T) (86.7 %) and Sphaerochaeta coccoides SPN1(T) (85.4 %). 25249566 12 62 theme pleomorpha 1371:1380 arg1 identity 1409:1416 88.4 % sequence identity 1393:1416 88.4 % sequence identity 1393:1416 16S rRNA gene-based phylogenetic analysis showed that strain MO-SPC2(T) was affiliated with the genus Sphaerochaeta within the phylum Spirochaetes, and its closest relatives were Sphaerochaeta pleomorpha Grapes(T) (88.4 % sequence identity), Sphaerochaeta globosa Buddy(T) (86.7 %) and Sphaerochaeta coccoides SPN1(T) (85.4 %). 25249566 1 63 theme Sphaerochaeta 147:159 arg1 description 122:132 emended description 114:132 emended description of the genus Sphaerochaeta 114:159 nov., an anaerobic, psychrophilic bacterium isolated from subseafloor sediment, and emended description of the genus Sphaerochaeta. 25249566 1 63 theme Sphaerochaeta 147:159 arg1 bacterium 64:72 an anaerobic, psychrophilic bacterium 36:72 an anaerobic, psychrophilic bacterium isolated from subseafloor sediment 36:107 nov., an anaerobic, psychrophilic bacterium isolated from subseafloor sediment, and emended description of the genus Sphaerochaeta. 25249566 1 63 theme Sphaerochaeta 147:159 arg1 nov. 30:33 nov. 30:33 nov. 30:33 nov., an anaerobic, psychrophilic bacterium isolated from subseafloor sediment, and emended description of the genus Sphaerochaeta. 25249566 7 64 theme end 832:834 arg1 acetate 874:880 acetate 874:880 acetate 874:880 The major end products of glucose fermentation were acetate, ethanol, hydrogen and carbon dioxide. 25249566 7 64 theme end 832:834 arg1 products 836:843 The major end products 822:843 The major end products of glucose fermentation 822:867 The major end products of glucose fermentation were acetate, ethanol, hydrogen and carbon dioxide. 25249566 12 65 theme closest 1334:1340 arg1 relatives 1342:1350 its closest relatives 1330:1350 its closest relatives 1330:1350 16S rRNA gene-based phylogenetic analysis showed that strain MO-SPC2(T) was affiliated with the genus Sphaerochaeta within the phylum Spirochaetes, and its closest relatives were Sphaerochaeta pleomorpha Grapes(T) (88.4 % sequence identity), Sphaerochaeta globosa Buddy(T) (86.7 %) and Sphaerochaeta coccoides SPN1(T) (85.4 %). 25249566 12 66 theme globosa 1434:1440 arg1 Buddy 1442:1446 Sphaerochaeta globosa Buddy 1420:1446 Sphaerochaeta globosa Buddy(T) (86.7 %) 1420:1458 16S rRNA gene-based phylogenetic analysis showed that strain MO-SPC2(T) was affiliated with the genus Sphaerochaeta within the phylum Spirochaetes, and its closest relatives were Sphaerochaeta pleomorpha Grapes(T) (88.4 % sequence identity), Sphaerochaeta globosa Buddy(T) (86.7 %) and Sphaerochaeta coccoides SPN1(T) (85.4 %). 25249566 12 66 theme globosa 1434:1440 arg1 % 1457:1457 86.7 % 1452:1457 86.7 % 1452:1457 16S rRNA gene-based phylogenetic analysis showed that strain MO-SPC2(T) was affiliated with the genus Sphaerochaeta within the phylum Spirochaetes, and its closest relatives were Sphaerochaeta pleomorpha Grapes(T) (88.4 % sequence identity), Sphaerochaeta globosa Buddy(T) (86.7 %) and Sphaerochaeta coccoides SPN1(T) (85.4 %). 25249566 12 66 theme globosa 1434:1440 arg1 T 1448:1448 T 1448:1448 T 1448:1448 16S rRNA gene-based phylogenetic analysis showed that strain MO-SPC2(T) was affiliated with the genus Sphaerochaeta within the phylum Spirochaetes, and its closest relatives were Sphaerochaeta pleomorpha Grapes(T) (88.4 % sequence identity), Sphaerochaeta globosa Buddy(T) (86.7 %) and Sphaerochaeta coccoides SPN1(T) (85.4 %). 25249566 10 67 theme Isoprenoid 1097:1106 arg1 quinones 1108:1115 Isoprenoid quinones 1097:1115 Isoprenoid quinones 1097:1115 Isoprenoid quinones were not detected. 25249566 0 68 theme multiformis 14:24 arg1 sp 26:27 Sphaerochaeta multiformis sp 0:27 Sphaerochaeta multiformis sp. 0:28 Sphaerochaeta multiformis sp. 25249566 8 69 theme abundant 925:932 arg1 lipids 940:945 The abundant polar lipids 921:945 The abundant polar lipids of strain MO-SPC2(T) 921:966 The abundant polar lipids of strain MO-SPC2(T) were phosphatidylglycolipids, phospholipids and glycolipids. 25249566 8 69 theme abundant 925:932 arg1 phosphatidylglycolipids 973:995 phosphatidylglycolipids 973:995 phosphatidylglycolipids 973:995 The abundant polar lipids of strain MO-SPC2(T) were phosphatidylglycolipids, phospholipids and glycolipids. 25249566 3 70 theme coccoid 509:515 arg1 morphologies 522:533 spherical, annular, curved rod, helical and coccoid cell morphologies 465:533 spherical, annular, curved rod, helical and coccoid cell morphologies 465:533 Cells were pleomorphic: spherical, annular, curved rod, helical and coccoid cell morphologies were observed. 25249566 2 71 theme Pacific 426:432 arg1 Ocean 434:438 the north-western Pacific Ocean 408:438 the north-western Pacific Ocean 408:438 An anaerobic, psychrophilic bacterium, strain MO-SPC2(T), was isolated from a methanogenic microbial community in a continuous-flow bioreactor that was established from subseafloor sediments collected from off the Shimokita Peninsula of Japan in the north-western Pacific Ocean. 25249566 15 72 theme type 1727:1730 arg1 MO-SPC2 1742:1748 MO-SPC2 1742:1748 MO-SPC2(T) ( = JCM 17281(T) = DSM 23952(T)) 1742:1784 The type strain is MO-SPC2(T) ( = JCM 17281(T) = DSM 23952(T)). 25249566 15 72 theme type 1727:1730 arg1 strain 1732:1737 The type strain 1723:1737 The type strain 1723:1737 The type strain is MO-SPC2(T) ( = JCM 17281(T) = DSM 23952(T)). 25249566 3 73 theme spherical 465:473 arg1 morphologies 522:533 spherical, annular, curved rod, helical and coccoid cell morphologies 465:533 spherical, annular, curved rod, helical and coccoid cell morphologies 465:533 Cells were pleomorphic: spherical, annular, curved rod, helical and coccoid cell morphologies were observed. 25249566 8 74 theme strain 950:955 arg1 T 965:965 T 965:965 T 965:965 The abundant polar lipids of strain MO-SPC2(T) were phosphatidylglycolipids, phospholipids and glycolipids. 25249566 8 74 theme strain 950:955 arg1 MO-SPC2 957:963 strain MO-SPC2 950:963 strain MO-SPC2(T) 950:966 The abundant polar lipids of strain MO-SPC2(T) were phosphatidylglycolipids, phospholipids and glycolipids. 25249566 11 75 theme mol 1172:1174 arg1 % 1175:1175 32.3 mol% 1167:1175 32.3 mol% 1167:1175 The G+C content of the DNA was 32.3 mol%. 25249566 11 75 theme mol 1172:1174 arg1 content 1144:1150 The G+C content 1136:1150 The G+C content of the DNA 1136:1161 The G+C content of the DNA was 32.3 mol%. 25249566 2 76 theme anaerobic 165:173 arg1 bacterium 190:198 An anaerobic, psychrophilic bacterium 162:198 An anaerobic, psychrophilic bacterium 162:198 An anaerobic, psychrophilic bacterium, strain MO-SPC2(T), was isolated from a methanogenic microbial community in a continuous-flow bioreactor that was established from subseafloor sediments collected from off the Shimokita Peninsula of Japan in the north-western Pacific Ocean. 25249566 2 76 theme anaerobic 165:173 arg1 MO-SPC2 208:214 strain MO-SPC2 201:214 strain MO-SPC2(T) 201:217 An anaerobic, psychrophilic bacterium, strain MO-SPC2(T), was isolated from a methanogenic microbial community in a continuous-flow bioreactor that was established from subseafloor sediments collected from off the Shimokita Peninsula of Japan in the north-western Pacific Ocean. 25249566 2 77 theme Japan 399:403 arg1 Peninsula 386:394 off the Shimokita Peninsula 368:394 off the Shimokita Peninsula of Japan in the north-western Pacific Ocean 368:438 An anaerobic, psychrophilic bacterium, strain MO-SPC2(T), was isolated from a methanogenic microbial community in a continuous-flow bioreactor that was established from subseafloor sediments collected from off the Shimokita Peninsula of Japan in the north-western Pacific Ocean. 25249566 5 78 theme NaCl 701:704 arg1 -1 708:709 -1 708:709 -1 708:709 Strain MO-SPC2(T) grew at 0-17 °C (optimally at 9 °C), at pH 6.0-8.0 (optimally at pH 6.8-7.2) and in 20-40 g NaCl l(-1) (optimally at 20-30 NaCl l(-1)). 25249566 5 78 theme NaCl 701:704 arg1 l 706:706 20-40 g NaCl l 693:706 20-40 g NaCl l(-1) (optimally at 20-30 NaCl l(-1)) 693:742 Strain MO-SPC2(T) grew at 0-17 °C (optimally at 9 °C), at pH 6.0-8.0 (optimally at pH 6.8-7.2) and in 20-40 g NaCl l(-1) (optimally at 20-30 NaCl l(-1)). 25249566 5 78 theme NaCl 701:704 arg1 l 737:737 optimally at 20-30 NaCl l(-1) 713:741 optimally at 20-30 NaCl l(-1) 713:741 Strain MO-SPC2(T) grew at 0-17 °C (optimally at 9 °C), at pH 6.0-8.0 (optimally at pH 6.8-7.2) and in 20-40 g NaCl l(-1) (optimally at 20-30 NaCl l(-1)). 25249566 12 79 theme phylum 1305:1310 arg1 Spirochaetes 1312:1323 the phylum Spirochaetes 1301:1323 the phylum Spirochaetes 1301:1323 16S rRNA gene-based phylogenetic analysis showed that strain MO-SPC2(T) was affiliated with the genus Sphaerochaeta within the phylum Spirochaetes, and its closest relatives were Sphaerochaeta pleomorpha Grapes(T) (88.4 % sequence identity), Sphaerochaeta globosa Buddy(T) (86.7 %) and Sphaerochaeta coccoides SPN1(T) (85.4 %). 25249566 15 80 theme  = DSM 1769:1774 arg1 23952 1776:1780  = JCM 17281(T) = DSM 23952 1754:1780  = JCM 17281(T) = DSM 23952(T) 1754:1783 The type strain is MO-SPC2(T) ( = JCM 17281(T) = DSM 23952(T)). 25249566 15 80 theme  = DSM 1769:1774 arg1 T 1782:1782 T 1782:1782 T 1782:1782 The type strain is MO-SPC2(T) ( = JCM 17281(T) = DSM 23952(T)). 25249566 1 81 theme anaerobic 39:47 arg1 bacterium 64:72 an anaerobic, psychrophilic bacterium 36:72 an anaerobic, psychrophilic bacterium isolated from subseafloor sediment 36:107 nov., an anaerobic, psychrophilic bacterium isolated from subseafloor sediment, and emended description of the genus Sphaerochaeta. 25249566 15 82 theme T 1767:1767 arg1 23952 1776:1780  = JCM 17281(T) = DSM 23952 1754:1780  = JCM 17281(T) = DSM 23952(T) 1754:1783 The type strain is MO-SPC2(T) ( = JCM 17281(T) = DSM 23952(T)). 25249566 15 82 theme T 1767:1767 arg1 T 1782:1782 T 1782:1782 T 1782:1782 The type strain is MO-SPC2(T) ( = JCM 17281(T) = DSM 23952(T)). 25249566 2 83 from Peninsula 386:394 arg1 Ocean 434:438 the north-western Pacific Ocean 408:438 the north-western Pacific Ocean 408:438 An anaerobic, psychrophilic bacterium, strain MO-SPC2(T), was isolated from a methanogenic microbial community in a continuous-flow bioreactor that was established from subseafloor sediments collected from off the Shimokita Peninsula of Japan in the north-western Pacific Ocean. 25249566 12 84 theme genus 1274:1278 arg1 Sphaerochaeta 1280:1292 the genus Sphaerochaeta 1270:1292 the genus Sphaerochaeta within the phylum Spirochaetes 1270:1323 16S rRNA gene-based phylogenetic analysis showed that strain MO-SPC2(T) was affiliated with the genus Sphaerochaeta within the phylum Spirochaetes, and its closest relatives were Sphaerochaeta pleomorpha Grapes(T) (88.4 % sequence identity), Sphaerochaeta globosa Buddy(T) (86.7 %) and Sphaerochaeta coccoides SPN1(T) (85.4 %). 25249566 15 85 theme 17281 1761:1765 arg1 23952 1776:1780  = JCM 17281(T) = DSM 23952 1754:1780  = JCM 17281(T) = DSM 23952(T) 1754:1783 The type strain is MO-SPC2(T) ( = JCM 17281(T) = DSM 23952(T)). 25249566 15 85 theme 17281 1761:1765 arg1 T 1782:1782 T 1782:1782 T 1782:1782 The type strain is MO-SPC2(T) ( = JCM 17281(T) = DSM 23952(T)). 25249566 16 86 theme genus 1817:1821 arg1 Sphaerochaeta 1823:1835 the genus Sphaerochaeta 1813:1835 the genus Sphaerochaeta 1813:1835 An emended description of the genus Sphaerochaeta is also proposed. 24440253 5 0 theme T-CS 933:936 arg1 group 938:942 the T-CS group 929:942 the T-CS group 929:942 This was followed by 4.6% reduction in rumination time of the T-CS group. 24440253 1 1 from performance 341:351 arg1 TMR 315:317 TMR 315:317 TMR 315:317 This study measured the effects of including 5% NaOH-treated corn straw (T-CS) as a substitute for 15% wheat hay in the control total mixed ration (TMR) of lactating cows on performance, digestibility, and rumen microbial profile. 24440253 1 1 from performance 341:351 arg1 ration 307:312 the control total mixed ration 283:312 the control total mixed ration (TMR) of lactating cows on performance, digestibility, and rumen microbial profile 283:395 This study measured the effects of including 5% NaOH-treated corn straw (T-CS) as a substitute for 15% wheat hay in the control total mixed ration (TMR) of lactating cows on performance, digestibility, and rumen microbial profile. 24440253 11 2 theme lactating 2045:2053 arg1 cow 2055:2057 the lactating cow 2041:2057 the lactating cow 2041:2057 These results illustrate the effect of T-CS on the composition of rumen microbiota, which may play a role in improving the performance of the lactating cow. 24440253 0 3 theme rumen 142:146 arg1 profile 158:164 rumen microbial profile 142:164 rumen microbial profile 142:164 Effects of including NaOH-treated corn straw as a substitute for wheat hay in the ration of lactating cows on performance, digestibility, and rumen microbial profile. 24440253 1 4 theme NaOH-treated 215:226 arg1 T-CS 240:243 T-CS 240:243 T-CS 240:243 This study measured the effects of including 5% NaOH-treated corn straw (T-CS) as a substitute for 15% wheat hay in the control total mixed ration (TMR) of lactating cows on performance, digestibility, and rumen microbial profile. 24440253 1 4 theme NaOH-treated 215:226 arg1 straw 233:237 5% NaOH-treated corn straw 212:237 5% NaOH-treated corn straw (T-CS) 212:244 This study measured the effects of including 5% NaOH-treated corn straw (T-CS) as a substitute for 15% wheat hay in the control total mixed ration (TMR) of lactating cows on performance, digestibility, and rumen microbial profile. 24440253 6 5 theme control 994:1000 arg1 cows 1002:1005 the control cows 990:1005 the control cows 990:1005 A slightly higher milk yield was observed in the control cows compared with the T-CS group; however, milk fat and milk protein content were higher in cows fed the T-CS TMR. 24440253 0 6 from digestibility 123:135 arg1 ration 82:87 the ration 78:87 the ration of lactating cows on performance, digestibility, and rumen microbial profile 78:164 Effects of including NaOH-treated corn straw as a substitute for wheat hay in the ration of lactating cows on performance, digestibility, and rumen microbial profile. 24440253 8 7 theme recumbence 1362:1371 arg1 time 1373:1376 daily recumbence time 1356:1376 daily recumbence time 1356:1376 Welfare of the cows, as assessed by length of daily recumbence time, was improved by feeding the T-CS TMR relative to the control group. 24440253 6 8 theme milk 1059:1062 arg1 content 1072:1078 milk protein content 1059:1078 milk protein content 1059:1078 A slightly higher milk yield was observed in the control cows compared with the T-CS group; however, milk fat and milk protein content were higher in cows fed the T-CS TMR. 24440253 7 9 theme energy-corrected 1230:1245 arg1 yield/intake 1252:1263 energy-corrected milk yield/intake 1230:1263 energy-corrected milk yield/intake 1230:1263 This was reflected in 1.3% increase in energy-corrected milk yield and 5.34% increase in production efficiency (energy-corrected milk yield/intake) of the T-CS cows compared with the control. 24440253 7 9 theme energy-corrected 1230:1245 arg1 efficiency 1218:1227 production efficiency 1207:1227 production efficiency (energy-corrected milk yield/intake) of the T-CS cows compared with the control 1207:1307 This was reflected in 1.3% increase in energy-corrected milk yield and 5.34% increase in production efficiency (energy-corrected milk yield/intake) of the T-CS cows compared with the control. 24440253 7 10 theme 5.34 1189:1192 arg1 % 1193:1193 % 1193:1193 % 1193:1193 This was reflected in 1.3% increase in energy-corrected milk yield and 5.34% increase in production efficiency (energy-corrected milk yield/intake) of the T-CS cows compared with the control. 24440253 9 11 from group 1529:1533 arg1 period 1555:1560 the experimental period 1538:1560 the experimental period compared with the preexperimental period 1538:1601 As a whole, the rumen bacterial community was significantly modulated in the T-CS group in the experimental period compared with the preexperimental period, whereas the bacterial community of the control group remained unchanged during this period. 24440253 4 12 theme Crude 692:696 arg1 digestibility 706:718 Crude protein digestibility 692:718 Crude protein digestibility 692:718 Crude protein digestibility was higher in the control cows but digestibility of neutral detergent fiber polysaccharides (cellulose and hemicelluloses) was higher in the T-CS TMR. 24440253 9 13 theme group 1651:1655 arg1 community 1626:1634 the bacterial community 1612:1634 the bacterial community of the control group 1612:1655 As a whole, the rumen bacterial community was significantly modulated in the T-CS group in the experimental period compared with the preexperimental period, whereas the bacterial community of the control group remained unchanged during this period. 24440253 1 14 theme microbial 379:387 arg1 profile 389:395 rumen microbial profile 373:395 rumen microbial profile 373:395 This study measured the effects of including 5% NaOH-treated corn straw (T-CS) as a substitute for 15% wheat hay in the control total mixed ration (TMR) of lactating cows on performance, digestibility, and rumen microbial profile. 24440253 6 15 theme T-CS 1025:1028 arg1 group 1030:1034 the T-CS group 1021:1034 the T-CS group 1021:1034 A slightly higher milk yield was observed in the control cows compared with the T-CS group; however, milk fat and milk protein content were higher in cows fed the T-CS TMR. 24440253 7 16 theme energy-corrected 1157:1172 arg1 yield 1179:1183 energy-corrected milk yield 1157:1183 energy-corrected milk yield 1157:1183 This was reflected in 1.3% increase in energy-corrected milk yield and 5.34% increase in production efficiency (energy-corrected milk yield/intake) of the T-CS cows compared with the control. 24440253 0 17 theme lactating 92:100 arg1 cows 102:105 lactating cows 92:105 lactating cows on performance, digestibility, and rumen microbial profile 92:164 Effects of including NaOH-treated corn straw as a substitute for wheat hay in the ration of lactating cows on performance, digestibility, and rumen microbial profile. 24440253 5 18 theme % 895:895 arg1 reduction 897:905 4.6% reduction 892:905 4.6% reduction in rumination time of the T-CS group 892:942 This was followed by 4.6% reduction in rumination time of the T-CS group. 24440253 4 19 theme neutral 772:778 arg1 polysaccharides 796:810 neutral detergent fiber polysaccharides 772:810 neutral detergent fiber polysaccharides (cellulose and hemicelluloses) 772:841 Crude protein digestibility was higher in the control cows but digestibility of neutral detergent fiber polysaccharides (cellulose and hemicelluloses) was higher in the T-CS TMR. 24440253 4 19 theme neutral 772:778 arg1 hemicelluloses 827:840 hemicelluloses 827:840 hemicelluloses 827:840 Crude protein digestibility was higher in the control cows but digestibility of neutral detergent fiber polysaccharides (cellulose and hemicelluloses) was higher in the T-CS TMR. 24440253 4 19 theme neutral 772:778 arg1 cellulose 813:821 cellulose 813:821 cellulose 813:821 Crude protein digestibility was higher in the control cows but digestibility of neutral detergent fiber polysaccharides (cellulose and hemicelluloses) was higher in the T-CS TMR. 24440253 10 20 theme T-CS 1833:1836 arg1 group 1838:1842 the T-CS group 1829:1842 the T-CS group 1829:1842 Out of the 8 bacterial species that were quantified using real-time PCR, a notable decrease in cellulolytic bacteria was observed in the T-CS group, as well as an increase in lactic acid-utilizing bacteria. 24440253 7 21 theme 1.3 1140:1142 arg1 % 1143:1143 % 1143:1143 % 1143:1143 This was reflected in 1.3% increase in energy-corrected milk yield and 5.34% increase in production efficiency (energy-corrected milk yield/intake) of the T-CS cows compared with the control. 24440253 10 22 theme lactic 1871:1876 arg1 bacteria 1893:1900 lactic acid-utilizing bacteria 1871:1900 lactic acid-utilizing bacteria 1871:1900 Out of the 8 bacterial species that were quantified using real-time PCR, a notable decrease in cellulolytic bacteria was observed in the T-CS group, as well as an increase in lactic acid-utilizing bacteria. 24440253 0 23 from ration 82:87 arg1 profile 158:164 rumen microbial profile 142:164 rumen microbial profile 142:164 Effects of including NaOH-treated corn straw as a substitute for wheat hay in the ration of lactating cows on performance, digestibility, and rumen microbial profile. 24440253 0 23 from ration 82:87 arg1 digestibility 123:135 digestibility 123:135 digestibility 123:135 Effects of including NaOH-treated corn straw as a substitute for wheat hay in the ration of lactating cows on performance, digestibility, and rumen microbial profile. 24440253 0 23 from ration 82:87 arg1 performance 110:120 performance 110:120 performance 110:120 Effects of including NaOH-treated corn straw as a substitute for wheat hay in the ration of lactating cows on performance, digestibility, and rumen microbial profile. 24440253 3 24 theme organic 632:638 arg1 matter 640:645 organic matter 632:645 organic matter 632:645 Voluntary dry matter intake of cows fed the control TMR was 4.3% higher than that of the T-CS cows, but in vivo dry matter and organic matter digestibilities of both groups were similar. 24440253 1 25 theme cows 333:336 arg1 TMR 315:317 TMR 315:317 TMR 315:317 This study measured the effects of including 5% NaOH-treated corn straw (T-CS) as a substitute for 15% wheat hay in the control total mixed ration (TMR) of lactating cows on performance, digestibility, and rumen microbial profile. 24440253 1 25 theme cows 333:336 arg1 ration 307:312 the control total mixed ration 283:312 the control total mixed ration (TMR) of lactating cows on performance, digestibility, and rumen microbial profile 283:395 This study measured the effects of including 5% NaOH-treated corn straw (T-CS) as a substitute for 15% wheat hay in the control total mixed ration (TMR) of lactating cows on performance, digestibility, and rumen microbial profile. 24440253 3 26 theme Voluntary 505:513 arg1 intake 526:531 Voluntary dry matter intake 505:531 Voluntary dry matter intake of cows fed the control TMR 505:559 Voluntary dry matter intake of cows fed the control TMR was 4.3% higher than that of the T-CS cows, but in vivo dry matter and organic matter digestibilities of both groups were similar. 24440253 9 27 theme rumen 1463:1467 arg1 community 1479:1487 the rumen bacterial community 1459:1487 the rumen bacterial community 1459:1487 As a whole, the rumen bacterial community was significantly modulated in the T-CS group in the experimental period compared with the preexperimental period, whereas the bacterial community of the control group remained unchanged during this period. 24440253 9 27 theme rumen 1463:1467 arg1 whole 1452:1456 whole 1452:1456 whole 1452:1456 As a whole, the rumen bacterial community was significantly modulated in the T-CS group in the experimental period compared with the preexperimental period, whereas the bacterial community of the control group remained unchanged during this period. 24440253 3 28 theme matter 621:626 arg1 digestibilities 647:661 in vivo dry matter and organic matter digestibilities 609:661 in vivo dry matter and organic matter digestibilities of both groups 609:676 Voluntary dry matter intake of cows fed the control TMR was 4.3% higher than that of the T-CS cows, but in vivo dry matter and organic matter digestibilities of both groups were similar. 24440253 6 29 located observed 978:985 arg1 cows 1002:1005 the control cows 990:1005 the control cows 990:1005 A slightly higher milk yield was observed in the control cows compared with the T-CS group; however, milk fat and milk protein content were higher in cows fed the T-CS TMR. 24440253 6 29 located observed 978:985 arg2 yield 968:972 A slightly higher milk yield 945:972 A slightly higher milk yield 945:972 A slightly higher milk yield was observed in the control cows compared with the T-CS group; however, milk fat and milk protein content were higher in cows fed the T-CS TMR. 24440253 5 30 theme group 938:942 arg1 time 921:924 rumination time 910:924 rumination time of the T-CS group 910:942 This was followed by 4.6% reduction in rumination time of the T-CS group. 24440253 0 31 theme wheat 65:69 arg1 hay 71:73 wheat hay 65:73 wheat hay 65:73 Effects of including NaOH-treated corn straw as a substitute for wheat hay in the ration of lactating cows on performance, digestibility, and rumen microbial profile. 24440253 7 32 from increase 1195:1202 arg1 yield 1179:1183 energy-corrected milk yield 1157:1183 energy-corrected milk yield 1157:1183 This was reflected in 1.3% increase in energy-corrected milk yield and 5.34% increase in production efficiency (energy-corrected milk yield/intake) of the T-CS cows compared with the control. 24440253 7 32 from increase 1195:1202 arg1 yield/intake 1252:1263 energy-corrected milk yield/intake 1230:1263 energy-corrected milk yield/intake 1230:1263 This was reflected in 1.3% increase in energy-corrected milk yield and 5.34% increase in production efficiency (energy-corrected milk yield/intake) of the T-CS cows compared with the control. 24440253 7 32 from increase 1195:1202 arg1 efficiency 1218:1227 production efficiency 1207:1227 production efficiency (energy-corrected milk yield/intake) of the T-CS cows compared with the control 1207:1307 This was reflected in 1.3% increase in energy-corrected milk yield and 5.34% increase in production efficiency (energy-corrected milk yield/intake) of the T-CS cows compared with the control. 24440253 4 33 theme fiber 790:794 arg1 polysaccharides 796:810 neutral detergent fiber polysaccharides 772:810 neutral detergent fiber polysaccharides (cellulose and hemicelluloses) 772:841 Crude protein digestibility was higher in the control cows but digestibility of neutral detergent fiber polysaccharides (cellulose and hemicelluloses) was higher in the T-CS TMR. 24440253 4 33 theme fiber 790:794 arg1 hemicelluloses 827:840 hemicelluloses 827:840 hemicelluloses 827:840 Crude protein digestibility was higher in the control cows but digestibility of neutral detergent fiber polysaccharides (cellulose and hemicelluloses) was higher in the T-CS TMR. 24440253 4 33 theme fiber 790:794 arg1 cellulose 813:821 cellulose 813:821 cellulose 813:821 Crude protein digestibility was higher in the control cows but digestibility of neutral detergent fiber polysaccharides (cellulose and hemicelluloses) was higher in the T-CS TMR. 24440253 10 34 from decrease 1779:1786 arg1 bacteria 1804:1811 cellulolytic bacteria 1791:1811 cellulolytic bacteria 1791:1811 Out of the 8 bacterial species that were quantified using real-time PCR, a notable decrease in cellulolytic bacteria was observed in the T-CS group, as well as an increase in lactic acid-utilizing bacteria. 24440253 2 35 theme cows 415:418 arg1 groups 402:407 Two groups 398:407 Two groups of 21 cows each 398:423 Two groups of 21 cows each, similar in initial performance, were fed individually 1 of the 2 TMR examined. 24440253 2 35 theme cows 415:418 arg1 cows 415:418 21 cows 412:418 21 cows 412:418 Two groups of 21 cows each, similar in initial performance, were fed individually 1 of the 2 TMR examined. 24440253 5 36 from reduction 897:905 arg1 time 921:924 rumination time 910:924 rumination time of the T-CS group 910:942 This was followed by 4.6% reduction in rumination time of the T-CS group. 24440253 1 37 theme total 295:299 arg1 TMR 315:317 TMR 315:317 TMR 315:317 This study measured the effects of including 5% NaOH-treated corn straw (T-CS) as a substitute for 15% wheat hay in the control total mixed ration (TMR) of lactating cows on performance, digestibility, and rumen microbial profile. 24440253 1 37 theme total 295:299 arg1 ration 307:312 the control total mixed ration 283:312 the control total mixed ration (TMR) of lactating cows on performance, digestibility, and rumen microbial profile 283:395 This study measured the effects of including 5% NaOH-treated corn straw (T-CS) as a substitute for 15% wheat hay in the control total mixed ration (TMR) of lactating cows on performance, digestibility, and rumen microbial profile. 24440253 9 38 theme T-CS 1524:1527 arg1 group 1529:1533 the T-CS group 1520:1533 the T-CS group in the experimental period compared with the preexperimental period 1520:1601 As a whole, the rumen bacterial community was significantly modulated in the T-CS group in the experimental period compared with the preexperimental period, whereas the bacterial community of the control group remained unchanged during this period. 24440253 0 39 from profile 158:164 arg1 ration 82:87 the ration 78:87 the ration of lactating cows on performance, digestibility, and rumen microbial profile 78:164 Effects of including NaOH-treated corn straw as a substitute for wheat hay in the ration of lactating cows on performance, digestibility, and rumen microbial profile. 24440253 10 40 located observed 1817:1824 arg1 group 1838:1842 the T-CS group 1829:1842 the T-CS group 1829:1842 Out of the 8 bacterial species that were quantified using real-time PCR, a notable decrease in cellulolytic bacteria was observed in the T-CS group, as well as an increase in lactic acid-utilizing bacteria. 24440253 10 40 located observed 1817:1824 arg2 decrease 1779:1786 a notable decrease 1769:1786 a notable decrease in cellulolytic bacteria 1769:1811 Out of the 8 bacterial species that were quantified using real-time PCR, a notable decrease in cellulolytic bacteria was observed in the T-CS group, as well as an increase in lactic acid-utilizing bacteria. 24440253 7 41 from increase 1145:1152 arg1 yield 1179:1183 energy-corrected milk yield 1157:1183 energy-corrected milk yield 1157:1183 This was reflected in 1.3% increase in energy-corrected milk yield and 5.34% increase in production efficiency (energy-corrected milk yield/intake) of the T-CS cows compared with the control. 24440253 7 41 from increase 1145:1152 arg1 yield/intake 1252:1263 energy-corrected milk yield/intake 1230:1263 energy-corrected milk yield/intake 1230:1263 This was reflected in 1.3% increase in energy-corrected milk yield and 5.34% increase in production efficiency (energy-corrected milk yield/intake) of the T-CS cows compared with the control. 24440253 7 41 from increase 1145:1152 arg1 efficiency 1218:1227 production efficiency 1207:1227 production efficiency (energy-corrected milk yield/intake) of the T-CS cows compared with the control 1207:1307 This was reflected in 1.3% increase in energy-corrected milk yield and 5.34% increase in production efficiency (energy-corrected milk yield/intake) of the T-CS cows compared with the control. 24440253 9 42 theme experimental 1542:1553 arg1 period 1555:1560 the experimental period 1538:1560 the experimental period compared with the preexperimental period 1538:1601 As a whole, the rumen bacterial community was significantly modulated in the T-CS group in the experimental period compared with the preexperimental period, whereas the bacterial community of the control group remained unchanged during this period. 24440253 0 43 theme corn 34:37 arg1 straw 39:43 NaOH-treated corn straw 21:43 NaOH-treated corn straw 21:43 Effects of including NaOH-treated corn straw as a substitute for wheat hay in the ration of lactating cows on performance, digestibility, and rumen microbial profile. 24440253 3 44 theme matter 519:524 arg1 intake 526:531 Voluntary dry matter intake 505:531 Voluntary dry matter intake of cows fed the control TMR 505:559 Voluntary dry matter intake of cows fed the control TMR was 4.3% higher than that of the T-CS cows, but in vivo dry matter and organic matter digestibilities of both groups were similar. 24440253 1 45 theme % 268:268 arg1 hay 276:278 15% wheat hay 266:278 15% wheat hay 266:278 This study measured the effects of including 5% NaOH-treated corn straw (T-CS) as a substitute for 15% wheat hay in the control total mixed ration (TMR) of lactating cows on performance, digestibility, and rumen microbial profile. 24440253 7 46 theme cows 1278:1281 arg1 yield/intake 1252:1263 energy-corrected milk yield/intake 1230:1263 energy-corrected milk yield/intake 1230:1263 This was reflected in 1.3% increase in energy-corrected milk yield and 5.34% increase in production efficiency (energy-corrected milk yield/intake) of the T-CS cows compared with the control. 24440253 7 46 theme cows 1278:1281 arg1 efficiency 1218:1227 production efficiency 1207:1227 production efficiency (energy-corrected milk yield/intake) of the T-CS cows compared with the control 1207:1307 This was reflected in 1.3% increase in energy-corrected milk yield and 5.34% increase in production efficiency (energy-corrected milk yield/intake) of the T-CS cows compared with the control. 24440253 1 47 from profile 389:395 arg1 TMR 315:317 TMR 315:317 TMR 315:317 This study measured the effects of including 5% NaOH-treated corn straw (T-CS) as a substitute for 15% wheat hay in the control total mixed ration (TMR) of lactating cows on performance, digestibility, and rumen microbial profile. 24440253 1 47 from profile 389:395 arg1 ration 307:312 the control total mixed ration 283:312 the control total mixed ration (TMR) of lactating cows on performance, digestibility, and rumen microbial profile 283:395 This study measured the effects of including 5% NaOH-treated corn straw (T-CS) as a substitute for 15% wheat hay in the control total mixed ration (TMR) of lactating cows on performance, digestibility, and rumen microbial profile. 24440253 10 48 theme cellulolytic 1791:1802 arg1 bacteria 1804:1811 cellulolytic bacteria 1791:1811 cellulolytic bacteria 1791:1811 Out of the 8 bacterial species that were quantified using real-time PCR, a notable decrease in cellulolytic bacteria was observed in the T-CS group, as well as an increase in lactic acid-utilizing bacteria. 24440253 3 49 theme control 549:555 arg1 TMR 557:559 the control TMR 545:559 the control TMR 545:559 Voluntary dry matter intake of cows fed the control TMR was 4.3% higher than that of the T-CS cows, but in vivo dry matter and organic matter digestibilities of both groups were similar. 24440253 10 50 theme bacterial 1709:1717 arg1 species 1719:1725 the 8 bacterial species 1703:1725 the 8 bacterial species that were quantified using real-time PCR 1703:1766 Out of the 8 bacterial species that were quantified using real-time PCR, a notable decrease in cellulolytic bacteria was observed in the T-CS group, as well as an increase in lactic acid-utilizing bacteria. 24440253 2 51 dep groups 402:407 arg1 each 420:423 each 420:423 each 420:423 Two groups of 21 cows each, similar in initial performance, were fed individually 1 of the 2 TMR examined. 24440253 2 52 from similar 426:432 arg1 performance 445:455 initial performance 437:455 initial performance 437:455 Two groups of 21 cows each, similar in initial performance, were fed individually 1 of the 2 TMR examined. 24440253 8 53 theme daily 1356:1360 arg1 time 1373:1376 daily recumbence time 1356:1376 daily recumbence time 1356:1376 Welfare of the cows, as assessed by length of daily recumbence time, was improved by feeding the T-CS TMR relative to the control group. 24440253 0 54 theme microbial 148:156 arg1 profile 158:164 rumen microbial profile 142:164 rumen microbial profile 142:164 Effects of including NaOH-treated corn straw as a substitute for wheat hay in the ration of lactating cows on performance, digestibility, and rumen microbial profile. 24440253 1 55 theme % 213:213 arg1 T-CS 240:243 T-CS 240:243 T-CS 240:243 This study measured the effects of including 5% NaOH-treated corn straw (T-CS) as a substitute for 15% wheat hay in the control total mixed ration (TMR) of lactating cows on performance, digestibility, and rumen microbial profile. 24440253 1 55 theme % 213:213 arg1 straw 233:237 5% NaOH-treated corn straw 212:237 5% NaOH-treated corn straw (T-CS) 212:244 This study measured the effects of including 5% NaOH-treated corn straw (T-CS) as a substitute for 15% wheat hay in the control total mixed ration (TMR) of lactating cows on performance, digestibility, and rumen microbial profile. 24440253 7 56 theme milk 1247:1250 arg1 yield/intake 1252:1263 energy-corrected milk yield/intake 1230:1263 energy-corrected milk yield/intake 1230:1263 This was reflected in 1.3% increase in energy-corrected milk yield and 5.34% increase in production efficiency (energy-corrected milk yield/intake) of the T-CS cows compared with the control. 24440253 7 56 theme milk 1247:1250 arg1 efficiency 1218:1227 production efficiency 1207:1227 production efficiency (energy-corrected milk yield/intake) of the T-CS cows compared with the control 1207:1307 This was reflected in 1.3% increase in energy-corrected milk yield and 5.34% increase in production efficiency (energy-corrected milk yield/intake) of the T-CS cows compared with the control. 24440253 4 57 theme protein 698:704 arg1 digestibility 706:718 Crude protein digestibility 692:718 Crude protein digestibility 692:718 Crude protein digestibility was higher in the control cows but digestibility of neutral detergent fiber polysaccharides (cellulose and hemicelluloses) was higher in the T-CS TMR. 24440253 9 58 theme bacterial 1616:1624 arg1 community 1626:1634 the bacterial community 1612:1634 the bacterial community of the control group 1612:1655 As a whole, the rumen bacterial community was significantly modulated in the T-CS group in the experimental period compared with the preexperimental period, whereas the bacterial community of the control group remained unchanged during this period. 24440253 8 59 theme time 1373:1376 arg1 length 1346:1351 length 1346:1351 length of daily recumbence time 1346:1376 Welfare of the cows, as assessed by length of daily recumbence time, was improved by feeding the T-CS TMR relative to the control group. 24440253 6 60 theme protein 1064:1070 arg1 content 1072:1078 milk protein content 1059:1078 milk protein content 1059:1078 A slightly higher milk yield was observed in the control cows compared with the T-CS group; however, milk fat and milk protein content were higher in cows fed the T-CS TMR. 24440253 1 61 theme corn 228:231 arg1 T-CS 240:243 T-CS 240:243 T-CS 240:243 This study measured the effects of including 5% NaOH-treated corn straw (T-CS) as a substitute for 15% wheat hay in the control total mixed ration (TMR) of lactating cows on performance, digestibility, and rumen microbial profile. 24440253 1 61 theme corn 228:231 arg1 straw 233:237 5% NaOH-treated corn straw 212:237 5% NaOH-treated corn straw (T-CS) 212:244 This study measured the effects of including 5% NaOH-treated corn straw (T-CS) as a substitute for 15% wheat hay in the control total mixed ration (TMR) of lactating cows on performance, digestibility, and rumen microbial profile. 24440253 11 62 theme microbiota 1975:1984 arg1 composition 1954:1964 the composition 1950:1964 the composition 1950:1964 These results illustrate the effect of T-CS on the composition of rumen microbiota, which may play a role in improving the performance of the lactating cow. 24440253 11 63 theme rumen 1969:1973 arg1 microbiota 1975:1984 rumen microbiota 1969:1984 rumen microbiota 1969:1984 These results illustrate the effect of T-CS on the composition of rumen microbiota, which may play a role in improving the performance of the lactating cow. 24440253 8 64 theme control 1432:1438 arg1 group 1440:1444 the control group 1428:1444 the control group 1428:1444 Welfare of the cows, as assessed by length of daily recumbence time, was improved by feeding the T-CS TMR relative to the control group. 24440253 7 65 theme production 1207:1216 arg1 yield/intake 1252:1263 energy-corrected milk yield/intake 1230:1263 energy-corrected milk yield/intake 1230:1263 This was reflected in 1.3% increase in energy-corrected milk yield and 5.34% increase in production efficiency (energy-corrected milk yield/intake) of the T-CS cows compared with the control. 24440253 7 65 theme production 1207:1216 arg1 efficiency 1218:1227 production efficiency 1207:1227 production efficiency (energy-corrected milk yield/intake) of the T-CS cows compared with the control 1207:1307 This was reflected in 1.3% increase in energy-corrected milk yield and 5.34% increase in production efficiency (energy-corrected milk yield/intake) of the T-CS cows compared with the control. 24440253 7 66 theme % 1193:1193 arg1 increase 1195:1202 5.34% increase 1189:1202 5.34% increase in production efficiency (energy-corrected milk yield/intake) of the T-CS cows compared with the control 1189:1307 This was reflected in 1.3% increase in energy-corrected milk yield and 5.34% increase in production efficiency (energy-corrected milk yield/intake) of the T-CS cows compared with the control. 24440253 9 67 theme control 1643:1649 arg1 group 1651:1655 the control group 1639:1655 the control group 1639:1655 As a whole, the rumen bacterial community was significantly modulated in the T-CS group in the experimental period compared with the preexperimental period, whereas the bacterial community of the control group remained unchanged during this period. 24440253 10 68 from increase 1859:1866 arg1 bacteria 1893:1900 lactic acid-utilizing bacteria 1871:1900 lactic acid-utilizing bacteria 1871:1900 Out of the 8 bacterial species that were quantified using real-time PCR, a notable decrease in cellulolytic bacteria was observed in the T-CS group, as well as an increase in lactic acid-utilizing bacteria. 24440253 6 69 theme milk 1046:1049 arg1 fat 1051:1053 milk fat 1046:1053 milk fat 1046:1053 A slightly higher milk yield was observed in the control cows compared with the T-CS group; however, milk fat and milk protein content were higher in cows fed the T-CS TMR. 24440253 1 70 theme rumen 373:377 arg1 profile 389:395 rumen microbial profile 373:395 rumen microbial profile 373:395 This study measured the effects of including 5% NaOH-treated corn straw (T-CS) as a substitute for 15% wheat hay in the control total mixed ration (TMR) of lactating cows on performance, digestibility, and rumen microbial profile. 24440253 2 71 theme TMR 491:493 arg1 1 480:480 1 480:480 1 480:480 Two groups of 21 cows each, similar in initial performance, were fed individually 1 of the 2 TMR examined. 24440253 2 71 theme TMR 491:493 arg1 TMR 491:493 the 2 TMR 485:493 the 2 TMR examined 485:502 Two groups of 21 cows each, similar in initial performance, were fed individually 1 of the 2 TMR examined. 24440253 0 72 theme cows 102:105 arg1 ration 82:87 the ration 78:87 the ration of lactating cows on performance, digestibility, and rumen microbial profile 78:164 Effects of including NaOH-treated corn straw as a substitute for wheat hay in the ration of lactating cows on performance, digestibility, and rumen microbial profile. 24440253 2 73 theme initial 437:443 arg1 performance 445:455 initial performance 437:455 initial performance 437:455 Two groups of 21 cows each, similar in initial performance, were fed individually 1 of the 2 TMR examined. 24440253 6 74 theme higher 956:961 arg1 yield 968:972 A slightly higher milk yield 945:972 A slightly higher milk yield 945:972 A slightly higher milk yield was observed in the control cows compared with the T-CS group; however, milk fat and milk protein content were higher in cows fed the T-CS TMR. 24440253 3 75 theme T-CS 594:597 arg1 cows 599:602 the T-CS cows 590:602 the T-CS cows 590:602 Voluntary dry matter intake of cows fed the control TMR was 4.3% higher than that of the T-CS cows, but in vivo dry matter and organic matter digestibilities of both groups were similar. 24440253 6 76 theme T-CS 1108:1111 arg1 TMR 1113:1115 the T-CS TMR 1104:1115 the T-CS TMR 1104:1115 A slightly higher milk yield was observed in the control cows compared with the T-CS group; however, milk fat and milk protein content were higher in cows fed the T-CS TMR. 24440253 2 77 theme similar 426:432 arg1 groups 402:407 Two groups 398:407 Two groups of 21 cows each 398:423 Two groups of 21 cows each, similar in initial performance, were fed individually 1 of the 2 TMR examined. 24440253 2 77 theme similar 426:432 arg1 cows 415:418 21 cows 412:418 21 cows 412:418 Two groups of 21 cows each, similar in initial performance, were fed individually 1 of the 2 TMR examined. 24440253 10 78 theme acid-utilizing 1878:1891 arg1 bacteria 1893:1900 lactic acid-utilizing bacteria 1871:1900 lactic acid-utilizing bacteria 1871:1900 Out of the 8 bacterial species that were quantified using real-time PCR, a notable decrease in cellulolytic bacteria was observed in the T-CS group, as well as an increase in lactic acid-utilizing bacteria. 24440253 3 79 theme dry 617:619 arg1 matter 621:626 in vivo dry matter 609:626 in vivo dry matter 609:626 Voluntary dry matter intake of cows fed the control TMR was 4.3% higher than that of the T-CS cows, but in vivo dry matter and organic matter digestibilities of both groups were similar. 24440253 5 80 theme rumination 910:919 arg1 time 921:924 rumination time 910:924 rumination time of the T-CS group 910:942 This was followed by 4.6% reduction in rumination time of the T-CS group. 24440253 7 81 theme % 1143:1143 arg1 increase 1145:1152 1.3% increase 1140:1152 1.3% increase in energy-corrected milk yield 1140:1183 This was reflected in 1.3% increase in energy-corrected milk yield and 5.34% increase in production efficiency (energy-corrected milk yield/intake) of the T-CS cows compared with the control. 24440253 3 82 theme in 609:610 arg1 matter 621:626 in vivo dry matter 609:626 in vivo dry matter 609:626 Voluntary dry matter intake of cows fed the control TMR was 4.3% higher than that of the T-CS cows, but in vivo dry matter and organic matter digestibilities of both groups were similar. 24440253 1 83 theme lactating 323:331 arg1 cows 333:336 lactating cows 323:336 lactating cows on performance, digestibility, and rumen microbial profile 323:395 This study measured the effects of including 5% NaOH-treated corn straw (T-CS) as a substitute for 15% wheat hay in the control total mixed ration (TMR) of lactating cows on performance, digestibility, and rumen microbial profile. 24440253 6 84 theme milk 963:966 arg1 yield 968:972 A slightly higher milk yield 945:972 A slightly higher milk yield 945:972 A slightly higher milk yield was observed in the control cows compared with the T-CS group; however, milk fat and milk protein content were higher in cows fed the T-CS TMR. 24440253 4 85 theme control 738:744 arg1 cows 746:749 the control cows 734:749 the control cows 734:749 Crude protein digestibility was higher in the control cows but digestibility of neutral detergent fiber polysaccharides (cellulose and hemicelluloses) was higher in the T-CS TMR. 24440253 3 86 theme matter 640:645 arg1 digestibilities 647:661 in vivo dry matter and organic matter digestibilities 609:661 in vivo dry matter and organic matter digestibilities of both groups 609:676 Voluntary dry matter intake of cows fed the control TMR was 4.3% higher than that of the T-CS cows, but in vivo dry matter and organic matter digestibilities of both groups were similar. 24440253 1 87 from cows 333:336 arg1 digestibility 354:366 digestibility 354:366 digestibility 354:366 This study measured the effects of including 5% NaOH-treated corn straw (T-CS) as a substitute for 15% wheat hay in the control total mixed ration (TMR) of lactating cows on performance, digestibility, and rumen microbial profile. 24440253 1 87 from cows 333:336 arg1 performance 341:351 performance 341:351 performance 341:351 This study measured the effects of including 5% NaOH-treated corn straw (T-CS) as a substitute for 15% wheat hay in the control total mixed ration (TMR) of lactating cows on performance, digestibility, and rumen microbial profile. 24440253 1 87 from cows 333:336 arg1 profile 389:395 rumen microbial profile 373:395 rumen microbial profile 373:395 This study measured the effects of including 5% NaOH-treated corn straw (T-CS) as a substitute for 15% wheat hay in the control total mixed ration (TMR) of lactating cows on performance, digestibility, and rumen microbial profile. 24440253 8 88 dep Welfare 1310:1316 arg1 assessed 1334:1341 assessed 1334:1341 assessed by length of daily recumbence time 1334:1376 Welfare of the cows, as assessed by length of daily recumbence time, was improved by feeding the T-CS TMR relative to the control group. 24440253 9 89 theme bacterial 1469:1477 arg1 community 1479:1487 the rumen bacterial community 1459:1487 the rumen bacterial community 1459:1487 As a whole, the rumen bacterial community was significantly modulated in the T-CS group in the experimental period compared with the preexperimental period, whereas the bacterial community of the control group remained unchanged during this period. 24440253 9 89 theme bacterial 1469:1477 arg1 whole 1452:1456 whole 1452:1456 whole 1452:1456 As a whole, the rumen bacterial community was significantly modulated in the T-CS group in the experimental period compared with the preexperimental period, whereas the bacterial community of the control group remained unchanged during this period. 24440253 1 90 theme wheat 270:274 arg1 hay 276:278 15% wheat hay 266:278 15% wheat hay 266:278 This study measured the effects of including 5% NaOH-treated corn straw (T-CS) as a substitute for 15% wheat hay in the control total mixed ration (TMR) of lactating cows on performance, digestibility, and rumen microbial profile. 24440253 4 91 dep polysaccharides 796:810 arg1 polysaccharides 796:810 neutral detergent fiber polysaccharides 772:810 neutral detergent fiber polysaccharides (cellulose and hemicelluloses) 772:841 Crude protein digestibility was higher in the control cows but digestibility of neutral detergent fiber polysaccharides (cellulose and hemicelluloses) was higher in the T-CS TMR. 24440253 4 91 dep polysaccharides 796:810 arg1 hemicelluloses 827:840 hemicelluloses 827:840 hemicelluloses 827:840 Crude protein digestibility was higher in the control cows but digestibility of neutral detergent fiber polysaccharides (cellulose and hemicelluloses) was higher in the T-CS TMR. 24440253 4 91 dep polysaccharides 796:810 arg1 cellulose 813:821 cellulose 813:821 cellulose 813:821 Crude protein digestibility was higher in the control cows but digestibility of neutral detergent fiber polysaccharides (cellulose and hemicelluloses) was higher in the T-CS TMR. 24440253 11 92 from effect 1932:1937 arg1 composition 1954:1964 the composition 1950:1964 the composition 1950:1964 These results illustrate the effect of T-CS on the composition of rumen microbiota, which may play a role in improving the performance of the lactating cow. 24440253 3 93 theme groups 671:676 arg1 digestibilities 647:661 in vivo dry matter and organic matter digestibilities 609:661 in vivo dry matter and organic matter digestibilities of both groups 609:676 Voluntary dry matter intake of cows fed the control TMR was 4.3% higher than that of the T-CS cows, but in vivo dry matter and organic matter digestibilities of both groups were similar. 24440253 7 94 theme milk 1174:1177 arg1 yield 1179:1183 energy-corrected milk yield 1157:1183 energy-corrected milk yield 1157:1183 This was reflected in 1.3% increase in energy-corrected milk yield and 5.34% increase in production efficiency (energy-corrected milk yield/intake) of the T-CS cows compared with the control. 24440253 4 95 theme detergent 780:788 arg1 polysaccharides 796:810 neutral detergent fiber polysaccharides 772:810 neutral detergent fiber polysaccharides (cellulose and hemicelluloses) 772:841 Crude protein digestibility was higher in the control cows but digestibility of neutral detergent fiber polysaccharides (cellulose and hemicelluloses) was higher in the T-CS TMR. 24440253 4 95 theme detergent 780:788 arg1 hemicelluloses 827:840 hemicelluloses 827:840 hemicelluloses 827:840 Crude protein digestibility was higher in the control cows but digestibility of neutral detergent fiber polysaccharides (cellulose and hemicelluloses) was higher in the T-CS TMR. 24440253 4 95 theme detergent 780:788 arg1 cellulose 813:821 cellulose 813:821 cellulose 813:821 Crude protein digestibility was higher in the control cows but digestibility of neutral detergent fiber polysaccharides (cellulose and hemicelluloses) was higher in the T-CS TMR. 24440253 11 96 theme cow 2055:2057 arg1 performance 2026:2036 the performance 2022:2036 the performance of the lactating cow 2022:2057 These results illustrate the effect of T-CS on the composition of rumen microbiota, which may play a role in improving the performance of the lactating cow. 24440253 10 97 theme real-time 1754:1762 arg1 PCR 1764:1766 real-time PCR 1754:1766 real-time PCR 1754:1766 Out of the 8 bacterial species that were quantified using real-time PCR, a notable decrease in cellulolytic bacteria was observed in the T-CS group, as well as an increase in lactic acid-utilizing bacteria. 24440253 1 98 from ration 307:312 arg1 digestibility 354:366 digestibility 354:366 digestibility 354:366 This study measured the effects of including 5% NaOH-treated corn straw (T-CS) as a substitute for 15% wheat hay in the control total mixed ration (TMR) of lactating cows on performance, digestibility, and rumen microbial profile. 24440253 1 98 from ration 307:312 arg1 performance 341:351 performance 341:351 performance 341:351 This study measured the effects of including 5% NaOH-treated corn straw (T-CS) as a substitute for 15% wheat hay in the control total mixed ration (TMR) of lactating cows on performance, digestibility, and rumen microbial profile. 24440253 1 98 from ration 307:312 arg1 profile 389:395 rumen microbial profile 373:395 rumen microbial profile 373:395 This study measured the effects of including 5% NaOH-treated corn straw (T-CS) as a substitute for 15% wheat hay in the control total mixed ration (TMR) of lactating cows on performance, digestibility, and rumen microbial profile. 24440253 1 99 theme control 287:293 arg1 TMR 315:317 TMR 315:317 TMR 315:317 This study measured the effects of including 5% NaOH-treated corn straw (T-CS) as a substitute for 15% wheat hay in the control total mixed ration (TMR) of lactating cows on performance, digestibility, and rumen microbial profile. 24440253 1 99 theme control 287:293 arg1 ration 307:312 the control total mixed ration 283:312 the control total mixed ration (TMR) of lactating cows on performance, digestibility, and rumen microbial profile 283:395 This study measured the effects of including 5% NaOH-treated corn straw (T-CS) as a substitute for 15% wheat hay in the control total mixed ration (TMR) of lactating cows on performance, digestibility, and rumen microbial profile. 24440253 4 100 theme polysaccharides 796:810 arg1 digestibility 755:767 digestibility 755:767 digestibility of neutral detergent fiber polysaccharides (cellulose and hemicelluloses) 755:841 Crude protein digestibility was higher in the control cows but digestibility of neutral detergent fiber polysaccharides (cellulose and hemicelluloses) was higher in the T-CS TMR. 24440253 1 101 dep a 249:249 arg1 substitute 251:260 substitute 251:260 substitute for 15% wheat hay in the control total mixed ration (TMR) of lactating cows on performance, digestibility, and rumen microbial profile 251:395 This study measured the effects of including 5% NaOH-treated corn straw (T-CS) as a substitute for 15% wheat hay in the control total mixed ration (TMR) of lactating cows on performance, digestibility, and rumen microbial profile. 24440253 11 102 theme T-CS 1942:1945 arg1 effect 1932:1937 the effect 1928:1937 the effect of T-CS on the composition of rumen microbiota, which may play a role in improving the performance of the lactating cow 1928:2057 These results illustrate the effect of T-CS on the composition of rumen microbiota, which may play a role in improving the performance of the lactating cow. 24440253 1 103 theme mixed 301:305 arg1 TMR 315:317 TMR 315:317 TMR 315:317 This study measured the effects of including 5% NaOH-treated corn straw (T-CS) as a substitute for 15% wheat hay in the control total mixed ration (TMR) of lactating cows on performance, digestibility, and rumen microbial profile. 24440253 1 103 theme mixed 301:305 arg1 ration 307:312 the control total mixed ration 283:312 the control total mixed ration (TMR) of lactating cows on performance, digestibility, and rumen microbial profile 283:395 This study measured the effects of including 5% NaOH-treated corn straw (T-CS) as a substitute for 15% wheat hay in the control total mixed ration (TMR) of lactating cows on performance, digestibility, and rumen microbial profile. 24440253 3 104 dep in 609:610 arg1 vivo 612:615 vivo 612:615 vivo 612:615 Voluntary dry matter intake of cows fed the control TMR was 4.3% higher than that of the T-CS cows, but in vivo dry matter and organic matter digestibilities of both groups were similar. 24440253 4 105 theme T-CS 861:864 arg1 TMR 866:868 the T-CS TMR 857:868 the T-CS TMR 857:868 Crude protein digestibility was higher in the control cows but digestibility of neutral detergent fiber polysaccharides (cellulose and hemicelluloses) was higher in the T-CS TMR. 24440253 0 106 theme NaOH-treated 21:32 arg1 straw 39:43 NaOH-treated corn straw 21:43 NaOH-treated corn straw 21:43 Effects of including NaOH-treated corn straw as a substitute for wheat hay in the ration of lactating cows on performance, digestibility, and rumen microbial profile. 24440253 8 107 theme cows 1325:1328 arg1 Welfare 1310:1316 Welfare 1310:1316 Welfare 1310:1316 Welfare of the cows, as assessed by length of daily recumbence time, was improved by feeding the T-CS TMR relative to the control group. 24440253 3 108 theme dry 515:517 arg1 intake 526:531 Voluntary dry matter intake 505:531 Voluntary dry matter intake of cows fed the control TMR 505:559 Voluntary dry matter intake of cows fed the control TMR was 4.3% higher than that of the T-CS cows, but in vivo dry matter and organic matter digestibilities of both groups were similar. 24440253 0 109 from cows 102:105 arg1 profile 158:164 rumen microbial profile 142:164 rumen microbial profile 142:164 Effects of including NaOH-treated corn straw as a substitute for wheat hay in the ration of lactating cows on performance, digestibility, and rumen microbial profile. 24440253 0 109 from cows 102:105 arg1 digestibility 123:135 digestibility 123:135 digestibility 123:135 Effects of including NaOH-treated corn straw as a substitute for wheat hay in the ration of lactating cows on performance, digestibility, and rumen microbial profile. 24440253 0 109 from cows 102:105 arg1 performance 110:120 performance 110:120 performance 110:120 Effects of including NaOH-treated corn straw as a substitute for wheat hay in the ration of lactating cows on performance, digestibility, and rumen microbial profile. 24440253 1 110 theme 15 266:267 arg1 % 268:268 % 268:268 % 268:268 This study measured the effects of including 5% NaOH-treated corn straw (T-CS) as a substitute for 15% wheat hay in the control total mixed ration (TMR) of lactating cows on performance, digestibility, and rumen microbial profile. 24440253 9 111 theme preexperimental 1580:1594 arg1 period 1596:1601 the preexperimental period 1576:1601 the preexperimental period 1576:1601 As a whole, the rumen bacterial community was significantly modulated in the T-CS group in the experimental period compared with the preexperimental period, whereas the bacterial community of the control group remained unchanged during this period. 24440253 0 112 from performance 110:120 arg1 ration 82:87 the ration 78:87 the ration of lactating cows on performance, digestibility, and rumen microbial profile 78:164 Effects of including NaOH-treated corn straw as a substitute for wheat hay in the ration of lactating cows on performance, digestibility, and rumen microbial profile. 24440253 3 113 theme cows 536:539 arg1 intake 526:531 Voluntary dry matter intake 505:531 Voluntary dry matter intake of cows fed the control TMR 505:559 Voluntary dry matter intake of cows fed the control TMR was 4.3% higher than that of the T-CS cows, but in vivo dry matter and organic matter digestibilities of both groups were similar. 24440253 8 114 theme T-CS 1407:1410 arg1 TMR 1412:1414 the T-CS TMR 1403:1414 the T-CS TMR relative to the control group 1403:1444 Welfare of the cows, as assessed by length of daily recumbence time, was improved by feeding the T-CS TMR relative to the control group. 24440253 7 115 theme T-CS 1273:1276 arg1 cows 1278:1281 the T-CS cows 1269:1281 the T-CS cows compared with the control 1269:1307 This was reflected in 1.3% increase in energy-corrected milk yield and 5.34% increase in production efficiency (energy-corrected milk yield/intake) of the T-CS cows compared with the control. 24440253 1 116 from digestibility 354:366 arg1 TMR 315:317 TMR 315:317 TMR 315:317 This study measured the effects of including 5% NaOH-treated corn straw (T-CS) as a substitute for 15% wheat hay in the control total mixed ration (TMR) of lactating cows on performance, digestibility, and rumen microbial profile. 24440253 1 116 from digestibility 354:366 arg1 ration 307:312 the control total mixed ration 283:312 the control total mixed ration (TMR) of lactating cows on performance, digestibility, and rumen microbial profile 283:395 This study measured the effects of including 5% NaOH-treated corn straw (T-CS) as a substitute for 15% wheat hay in the control total mixed ration (TMR) of lactating cows on performance, digestibility, and rumen microbial profile. 24440253 10 117 theme notable 1771:1777 arg1 decrease 1779:1786 a notable decrease 1769:1786 a notable decrease in cellulolytic bacteria 1769:1811 Out of the 8 bacterial species that were quantified using real-time PCR, a notable decrease in cellulolytic bacteria was observed in the T-CS group, as well as an increase in lactic acid-utilizing bacteria. 24440253 2 118 from performance 445:455 arg1 similar 426:432 similar 426:432 similar 426:432 Two groups of 21 cows each, similar in initial performance, were fed individually 1 of the 2 TMR examined. 24440253 8 119 theme relative 1416:1423 arg1 TMR 1412:1414 the T-CS TMR 1403:1414 the T-CS TMR relative to the control group 1403:1444 Welfare of the cows, as assessed by length of daily recumbence time, was improved by feeding the T-CS TMR relative to the control group. 24440253 1 120 theme 5 212:212 arg1 % 213:213 % 213:213 % 213:213 This study measured the effects of including 5% NaOH-treated corn straw (T-CS) as a substitute for 15% wheat hay in the control total mixed ration (TMR) of lactating cows on performance, digestibility, and rumen microbial profile. 28618655 0 0 theme potential 58:66 arg1 tool 84:87 a potential pharmacological tool 56:87 Eugenia uniflora fruit (red type) standardized extract: a potential pharmacological tool to diet-induced metabolic syndrome damage management. 0:141 Eugenia uniflora fruit (red type) standardized extract: a potential pharmacological tool to diet-induced metabolic syndrome damage management. 28618655 6 1 theme forced 1249:1254 arg1 test 1261:1264 the forced swim test 1245:1264 the forced swim test 1245:1264 The extract prevented increased acetylcholinesterase activity in the prefrontal cortex caused by HPD and the increase in immobility time observed in the forced swim test. 28618655 1 2 from parameters 304:313 arg1 model 328:332 an animal model 318:332 an animal model of metabolic syndrome induced by a highly palatable diet (HPD) 318:395 The aim of this study was to investigate the effect of Eugenia uniflora fruit (red type) extract on metabolic status, as well as on neurochemical and behavioral parameters in an animal model of metabolic syndrome induced by a highly palatable diet (HPD). 28618655 2 3 dep 200mg/kg 533:540 arg1 p.o 549:551 p.o 549:551 p.o 549:551 Rats were treated for 150days and divided into 4 experimental groups: standard chow (SC) and water orally, SC and E. uniflora extract (200mg/kg daily, p.o), HPD and water orally, HPD and extract. 28618655 1 4 theme red 222:224 arg1 extract 232:238 Eugenia uniflora fruit (red type) extract 198:238 Eugenia uniflora fruit (red type) extract 198:238 The aim of this study was to investigate the effect of Eugenia uniflora fruit (red type) extract on metabolic status, as well as on neurochemical and behavioral parameters in an animal model of metabolic syndrome induced by a highly palatable diet (HPD). 28618655 7 5 theme major 1362:1366 arg1 compounds 1368:1376 the major compounds 1358:1376 the major compounds 1358:1376 Regarding chemical composition, LC/MS analysis showed the presence of nine anthocyanins as the major compounds. 28618655 1 6 theme behavioral 293:302 arg1 parameters 304:313 neurochemical and behavioral parameters 275:313 neurochemical and behavioral parameters in an animal model of metabolic syndrome induced by a highly palatable diet (HPD) 275:395 The aim of this study was to investigate the effect of Eugenia uniflora fruit (red type) extract on metabolic status, as well as on neurochemical and behavioral parameters in an animal model of metabolic syndrome induced by a highly palatable diet (HPD). 28618655 6 7 located observed 1233:1240 arg2 time 1228:1231 immobility time 1217:1231 immobility time observed in the forced swim test 1217:1264 The extract prevented increased acetylcholinesterase activity in the prefrontal cortex caused by HPD and the increase in immobility time observed in the forced swim test. 28618655 6 7 located observed 1233:1240 arg1 test 1261:1264 the forced swim test 1245:1264 the forced swim test 1245:1264 The extract prevented increased acetylcholinesterase activity in the prefrontal cortex caused by HPD and the increase in immobility time observed in the forced swim test. 28618655 4 8 theme activities 922:931 arg1 reduction 875:883 the reduction 871:883 the reduction of superoxide dismutase and catalase activities in the prefrontal cortex, hippocampus and striatum of animals submitted to HPD 871:1010 The extract decreased lipid peroxidation and prevented the reduction of superoxide dismutase and catalase activities in the prefrontal cortex, hippocampus and striatum of animals submitted to HPD. 28618655 1 9 theme type 226:229 arg1 extract 232:238 Eugenia uniflora fruit (red type) extract 198:238 Eugenia uniflora fruit (red type) extract 198:238 The aim of this study was to investigate the effect of Eugenia uniflora fruit (red type) extract on metabolic status, as well as on neurochemical and behavioral parameters in an animal model of metabolic syndrome induced by a highly palatable diet (HPD). 28618655 4 10 theme catalase 913:920 arg1 activities 922:931 superoxide dismutase and catalase activities 888:931 superoxide dismutase and catalase activities 888:931 The extract decreased lipid peroxidation and prevented the reduction of superoxide dismutase and catalase activities in the prefrontal cortex, hippocampus and striatum of animals submitted to HPD. 28618655 3 11 theme weight 671:676 arg1 gain 678:681 weight gain 671:681 weight gain 671:681 Our data showed that HPD caused glucose intolerance, increased visceral fat, weight gain, as well as serum glucose, triacylglycerol, total cholesterol and LDL cholesterol; however, E. uniflora prevented these alterations. 28618655 3 11 theme weight 671:676 arg1 intolerance 634:644 glucose intolerance 626:644 glucose intolerance 626:644 Our data showed that HPD caused glucose intolerance, increased visceral fat, weight gain, as well as serum glucose, triacylglycerol, total cholesterol and LDL cholesterol; however, E. uniflora prevented these alterations. 28618655 0 12 theme pharmacological 68:82 arg1 tool 84:87 a potential pharmacological tool 56:87 Eugenia uniflora fruit (red type) standardized extract: a potential pharmacological tool to diet-induced metabolic syndrome damage management. 0:141 Eugenia uniflora fruit (red type) standardized extract: a potential pharmacological tool to diet-induced metabolic syndrome damage management. 28618655 8 13 theme E. 1394:1395 arg1 extract 1406:1412 E. uniflora extract 1394:1412 E. uniflora extract 1394:1412 In conclusion, E. uniflora extract showed benefits against metabolic alterations caused by HPD, as well as exhibited antioxidant and antidepressant-like effects. 28618655 3 14 theme LDL 749:751 arg1 cholesterol 753:763 LDL cholesterol 749:763 LDL cholesterol 749:763 Our data showed that HPD caused glucose intolerance, increased visceral fat, weight gain, as well as serum glucose, triacylglycerol, total cholesterol and LDL cholesterol; however, E. uniflora prevented these alterations. 28618655 3 14 theme LDL 749:751 arg1 intolerance 634:644 glucose intolerance 626:644 glucose intolerance 626:644 Our data showed that HPD caused glucose intolerance, increased visceral fat, weight gain, as well as serum glucose, triacylglycerol, total cholesterol and LDL cholesterol; however, E. uniflora prevented these alterations. 28618655 1 15 theme extract 232:238 arg1 effect 188:193 the effect 184:193 the effect of Eugenia uniflora fruit (red type) extract on metabolic status, as well as on neurochemical and behavioral parameters in an animal model of metabolic syndrome induced by a highly palatable diet (HPD) 184:395 The aim of this study was to investigate the effect of Eugenia uniflora fruit (red type) extract on metabolic status, as well as on neurochemical and behavioral parameters in an animal model of metabolic syndrome induced by a highly palatable diet (HPD). 28618655 0 16 theme diet-induced 92:103 arg1 management 131:140 diet-induced metabolic syndrome damage management 92:140 diet-induced metabolic syndrome damage management 92:140 Eugenia uniflora fruit (red type) standardized extract: a potential pharmacological tool to diet-induced metabolic syndrome damage management. 28618655 4 17 theme animals 987:993 arg1 striatum 975:982 striatum 975:982 striatum 975:982 The extract decreased lipid peroxidation and prevented the reduction of superoxide dismutase and catalase activities in the prefrontal cortex, hippocampus and striatum of animals submitted to HPD. 28618655 4 17 theme animals 987:993 arg1 hippocampus 959:969 hippocampus 959:969 hippocampus 959:969 The extract decreased lipid peroxidation and prevented the reduction of superoxide dismutase and catalase activities in the prefrontal cortex, hippocampus and striatum of animals submitted to HPD. 28618655 4 17 theme animals 987:993 arg1 cortex 951:956 the prefrontal cortex 936:956 the prefrontal cortex 936:956 The extract decreased lipid peroxidation and prevented the reduction of superoxide dismutase and catalase activities in the prefrontal cortex, hippocampus and striatum of animals submitted to HPD. 28618655 5 18 from reduction 1039:1047 arg1 structures 1084:1093 these cerebral structures 1069:1093 these cerebral structures 1069:1093 We observed a HPD-induced reduction of thiol content in these cerebral structures. 28618655 3 19 theme total 727:731 arg1 cholesterol 733:743 total cholesterol 727:743 total cholesterol 727:743 Our data showed that HPD caused glucose intolerance, increased visceral fat, weight gain, as well as serum glucose, triacylglycerol, total cholesterol and LDL cholesterol; however, E. uniflora prevented these alterations. 28618655 3 19 theme total 727:731 arg1 intolerance 634:644 glucose intolerance 626:644 glucose intolerance 626:644 Our data showed that HPD caused glucose intolerance, increased visceral fat, weight gain, as well as serum glucose, triacylglycerol, total cholesterol and LDL cholesterol; however, E. uniflora prevented these alterations. 28618655 6 20 theme immobility 1217:1226 arg1 time 1228:1231 immobility time 1217:1231 immobility time observed in the forced swim test 1217:1264 The extract prevented increased acetylcholinesterase activity in the prefrontal cortex caused by HPD and the increase in immobility time observed in the forced swim test. 28618655 1 21 theme animal 321:326 arg1 model 328:332 an animal model 318:332 an animal model of metabolic syndrome induced by a highly palatable diet (HPD) 318:395 The aim of this study was to investigate the effect of Eugenia uniflora fruit (red type) extract on metabolic status, as well as on neurochemical and behavioral parameters in an animal model of metabolic syndrome induced by a highly palatable diet (HPD). 28618655 5 22 theme thiol 1052:1056 arg1 content 1058:1064 thiol content 1052:1064 thiol content 1052:1064 We observed a HPD-induced reduction of thiol content in these cerebral structures. 28618655 6 23 from activity 1149:1156 arg1 cortex 1176:1181 the prefrontal cortex 1161:1181 the prefrontal cortex caused by HPD and the increase in immobility time observed in the forced swim test 1161:1264 The extract prevented increased acetylcholinesterase activity in the prefrontal cortex caused by HPD and the increase in immobility time observed in the forced swim test. 28618655 1 24 theme study 159:163 arg1 aim 147:149 The aim 143:149 The aim of this study 143:163 The aim of this study was to investigate the effect of Eugenia uniflora fruit (red type) extract on metabolic status, as well as on neurochemical and behavioral parameters in an animal model of metabolic syndrome induced by a highly palatable diet (HPD). 28618655 0 25 theme uniflora 8:15 arg1 extract 47:53 Eugenia uniflora fruit (red type) standardized extract 0:53 Eugenia uniflora fruit (red type) standardized extract: a potential pharmacological tool to diet-induced metabolic syndrome damage management. 0:141 Eugenia uniflora fruit (red type) standardized extract: a potential pharmacological tool to diet-induced metabolic syndrome damage management. 28618655 8 26 theme uniflora 1397:1404 arg1 extract 1406:1412 E. uniflora extract 1394:1412 E. uniflora extract 1394:1412 In conclusion, E. uniflora extract showed benefits against metabolic alterations caused by HPD, as well as exhibited antioxidant and antidepressant-like effects. 28618655 2 27 theme uniflora 515:522 arg1 extract 524:530 uniflora extract 515:530 uniflora extract 515:530 Rats were treated for 150days and divided into 4 experimental groups: standard chow (SC) and water orally, SC and E. uniflora extract (200mg/kg daily, p.o), HPD and water orally, HPD and extract. 28618655 7 28 theme chemical 1277:1284 arg1 composition 1286:1296 chemical composition 1277:1296 chemical composition 1277:1296 Regarding chemical composition, LC/MS analysis showed the presence of nine anthocyanins as the major compounds. 28618655 0 29 theme Eugenia 0:6 arg1 extract 47:53 Eugenia uniflora fruit (red type) standardized extract 0:53 Eugenia uniflora fruit (red type) standardized extract: a potential pharmacological tool to diet-induced metabolic syndrome damage management. 0:141 Eugenia uniflora fruit (red type) standardized extract: a potential pharmacological tool to diet-induced metabolic syndrome damage management. 28618655 6 30 theme acetylcholinesterase 1128:1147 arg1 activity 1149:1156 increased acetylcholinesterase activity 1118:1156 increased acetylcholinesterase activity in the prefrontal cortex caused by HPD and the increase in immobility time observed in the forced swim test 1118:1264 The extract prevented increased acetylcholinesterase activity in the prefrontal cortex caused by HPD and the increase in immobility time observed in the forced swim test. 28618655 8 31 theme antioxidant 1496:1506 arg1 effects 1532:1538 antioxidant and antidepressant-like effects 1496:1538 antioxidant and antidepressant-like effects 1496:1538 In conclusion, E. uniflora extract showed benefits against metabolic alterations caused by HPD, as well as exhibited antioxidant and antidepressant-like effects. 28618655 4 32 theme superoxide 888:897 arg1 dismutase 899:907 superoxide dismutase 888:907 superoxide dismutase 888:907 The extract decreased lipid peroxidation and prevented the reduction of superoxide dismutase and catalase activities in the prefrontal cortex, hippocampus and striatum of animals submitted to HPD. 28618655 1 33 theme metabolic 243:251 arg1 status 253:258 metabolic status 243:258 metabolic status 243:258 The aim of this study was to investigate the effect of Eugenia uniflora fruit (red type) extract on metabolic status, as well as on neurochemical and behavioral parameters in an animal model of metabolic syndrome induced by a highly palatable diet (HPD). 28618655 0 34 theme syndrome 115:122 arg1 management 131:140 diet-induced metabolic syndrome damage management 92:140 diet-induced metabolic syndrome damage management 92:140 Eugenia uniflora fruit (red type) standardized extract: a potential pharmacological tool to diet-induced metabolic syndrome damage management. 28618655 2 35 dep groups 460:465 arg1 SC 505:506 SC 505:506 SC 505:506 Rats were treated for 150days and divided into 4 experimental groups: standard chow (SC) and water orally, SC and E. uniflora extract (200mg/kg daily, p.o), HPD and water orally, HPD and extract. 28618655 2 35 dep groups 460:465 arg1 extract 585:591 extract 585:591 extract 585:591 Rats were treated for 150days and divided into 4 experimental groups: standard chow (SC) and water orally, SC and E. uniflora extract (200mg/kg daily, p.o), HPD and water orally, HPD and extract. 28618655 2 35 dep groups 460:465 arg1 200mg/kg 533:540 200mg/kg 533:540 200mg/kg daily 533:546 Rats were treated for 150days and divided into 4 experimental groups: standard chow (SC) and water orally, SC and E. uniflora extract (200mg/kg daily, p.o), HPD and water orally, HPD and extract. 28618655 2 35 dep groups 460:465 arg1 SC 483:484 SC 483:484 SC 483:484 Rats were treated for 150days and divided into 4 experimental groups: standard chow (SC) and water orally, SC and E. uniflora extract (200mg/kg daily, p.o), HPD and water orally, HPD and extract. 28618655 2 35 dep groups 460:465 arg1 groups 460:465 4 experimental groups 445:465 4 experimental groups: standard chow (SC) and water orally, SC and E. uniflora extract (200mg/kg daily, p.o), HPD and water orally, HPD and extract 445:591 Rats were treated for 150days and divided into 4 experimental groups: standard chow (SC) and water orally, SC and E. uniflora extract (200mg/kg daily, p.o), HPD and water orally, HPD and extract. 28618655 2 35 dep groups 460:465 arg1 water 491:495 water 491:495 water 491:495 Rats were treated for 150days and divided into 4 experimental groups: standard chow (SC) and water orally, SC and E. uniflora extract (200mg/kg daily, p.o), HPD and water orally, HPD and extract. 28618655 2 35 dep groups 460:465 arg1 HPD 577:579 HPD 577:579 HPD 577:579 Rats were treated for 150days and divided into 4 experimental groups: standard chow (SC) and water orally, SC and E. uniflora extract (200mg/kg daily, p.o), HPD and water orally, HPD and extract. 28618655 2 35 dep groups 460:465 arg1 chow 477:480 standard chow 468:480 standard chow (SC) 468:485 Rats were treated for 150days and divided into 4 experimental groups: standard chow (SC) and water orally, SC and E. uniflora extract (200mg/kg daily, p.o), HPD and water orally, HPD and extract. 28618655 2 35 dep groups 460:465 arg1 HPD 555:557 HPD 555:557 HPD 555:557 Rats were treated for 150days and divided into 4 experimental groups: standard chow (SC) and water orally, SC and E. uniflora extract (200mg/kg daily, p.o), HPD and water orally, HPD and extract. 28618655 0 36 theme fruit 17:21 arg1 extract 47:53 Eugenia uniflora fruit (red type) standardized extract 0:53 Eugenia uniflora fruit (red type) standardized extract: a potential pharmacological tool to diet-induced metabolic syndrome damage management. 0:141 Eugenia uniflora fruit (red type) standardized extract: a potential pharmacological tool to diet-induced metabolic syndrome damage management. 28618655 4 37 from reduction 875:883 arg1 striatum 975:982 striatum 975:982 striatum 975:982 The extract decreased lipid peroxidation and prevented the reduction of superoxide dismutase and catalase activities in the prefrontal cortex, hippocampus and striatum of animals submitted to HPD. 28618655 4 37 from reduction 875:883 arg1 hippocampus 959:969 hippocampus 959:969 hippocampus 959:969 The extract decreased lipid peroxidation and prevented the reduction of superoxide dismutase and catalase activities in the prefrontal cortex, hippocampus and striatum of animals submitted to HPD. 28618655 4 37 from reduction 875:883 arg1 cortex 951:956 the prefrontal cortex 936:956 the prefrontal cortex 936:956 The extract decreased lipid peroxidation and prevented the reduction of superoxide dismutase and catalase activities in the prefrontal cortex, hippocampus and striatum of animals submitted to HPD. 28618655 0 38 theme metabolic 105:113 arg1 management 131:140 diet-induced metabolic syndrome damage management 92:140 diet-induced metabolic syndrome damage management 92:140 Eugenia uniflora fruit (red type) standardized extract: a potential pharmacological tool to diet-induced metabolic syndrome damage management. 28618655 0 39 dep extract 47:53 arg1 tool 84:87 a potential pharmacological tool 56:87 Eugenia uniflora fruit (red type) standardized extract: a potential pharmacological tool to diet-induced metabolic syndrome damage management. 0:141 Eugenia uniflora fruit (red type) standardized extract: a potential pharmacological tool to diet-induced metabolic syndrome damage management. 28618655 8 40 theme metabolic 1438:1446 arg1 alterations 1448:1458 metabolic alterations 1438:1458 metabolic alterations caused by HPD 1438:1472 In conclusion, E. uniflora extract showed benefits against metabolic alterations caused by HPD, as well as exhibited antioxidant and antidepressant-like effects. 28618655 0 41 theme type 28:31 arg1 extract 47:53 Eugenia uniflora fruit (red type) standardized extract 0:53 Eugenia uniflora fruit (red type) standardized extract: a potential pharmacological tool to diet-induced metabolic syndrome damage management. 0:141 Eugenia uniflora fruit (red type) standardized extract: a potential pharmacological tool to diet-induced metabolic syndrome damage management. 28618655 6 42 from increase 1205:1212 arg1 time 1228:1231 immobility time 1217:1231 immobility time observed in the forced swim test 1217:1264 The extract prevented increased acetylcholinesterase activity in the prefrontal cortex caused by HPD and the increase in immobility time observed in the forced swim test. 28618655 2 43 theme standard 468:475 arg1 chow 477:480 standard chow 468:480 standard chow (SC) 468:485 Rats were treated for 150days and divided into 4 experimental groups: standard chow (SC) and water orally, SC and E. uniflora extract (200mg/kg daily, p.o), HPD and water orally, HPD and extract. 28618655 2 43 theme standard 468:475 arg1 SC 483:484 SC 483:484 SC 483:484 Rats were treated for 150days and divided into 4 experimental groups: standard chow (SC) and water orally, SC and E. uniflora extract (200mg/kg daily, p.o), HPD and water orally, HPD and extract. 28618655 2 43 theme standard 468:475 arg1 groups 460:465 4 experimental groups 445:465 4 experimental groups: standard chow (SC) and water orally, SC and E. uniflora extract (200mg/kg daily, p.o), HPD and water orally, HPD and extract 445:591 Rats were treated for 150days and divided into 4 experimental groups: standard chow (SC) and water orally, SC and E. uniflora extract (200mg/kg daily, p.o), HPD and water orally, HPD and extract. 28618655 1 44 theme metabolic 337:345 arg1 syndrome 347:354 metabolic syndrome 337:354 metabolic syndrome induced by a highly palatable diet (HPD) 337:395 The aim of this study was to investigate the effect of Eugenia uniflora fruit (red type) extract on metabolic status, as well as on neurochemical and behavioral parameters in an animal model of metabolic syndrome induced by a highly palatable diet (HPD). 28618655 6 45 theme prefrontal 1165:1174 arg1 cortex 1176:1181 the prefrontal cortex 1161:1181 the prefrontal cortex caused by HPD and the increase in immobility time observed in the forced swim test 1161:1264 The extract prevented increased acetylcholinesterase activity in the prefrontal cortex caused by HPD and the increase in immobility time observed in the forced swim test. 28618655 5 46 theme content 1058:1064 arg1 reduction 1039:1047 a HPD-induced reduction 1025:1047 a HPD-induced reduction of thiol content in these cerebral structures 1025:1093 We observed a HPD-induced reduction of thiol content in these cerebral structures. 28618655 0 47 theme red 24:26 arg1 type 28:31 red type 24:31 Eugenia uniflora fruit (red type) standardized extract: a potential pharmacological tool to diet-induced metabolic syndrome damage management. 0:141 Eugenia uniflora fruit (red type) standardized extract: a potential pharmacological tool to diet-induced metabolic syndrome damage management. 28618655 7 48 theme anthocyanins 1342:1353 arg1 presence 1325:1332 the presence 1321:1332 the presence of nine anthocyanins as the major compounds 1321:1376 Regarding chemical composition, LC/MS analysis showed the presence of nine anthocyanins as the major compounds. 28618655 0 49 theme damage 124:129 arg1 management 131:140 diet-induced metabolic syndrome damage management 92:140 diet-induced metabolic syndrome damage management 92:140 Eugenia uniflora fruit (red type) standardized extract: a potential pharmacological tool to diet-induced metabolic syndrome damage management. 28618655 1 50 theme syndrome 347:354 arg1 model 328:332 an animal model 318:332 an animal model of metabolic syndrome induced by a highly palatable diet (HPD) 318:395 The aim of this study was to investigate the effect of Eugenia uniflora fruit (red type) extract on metabolic status, as well as on neurochemical and behavioral parameters in an animal model of metabolic syndrome induced by a highly palatable diet (HPD). 28618655 3 51 theme increased 647:655 arg1 fat 666:668 increased visceral fat 647:668 increased visceral fat 647:668 Our data showed that HPD caused glucose intolerance, increased visceral fat, weight gain, as well as serum glucose, triacylglycerol, total cholesterol and LDL cholesterol; however, E. uniflora prevented these alterations. 28618655 3 51 theme increased 647:655 arg1 intolerance 634:644 glucose intolerance 626:644 glucose intolerance 626:644 Our data showed that HPD caused glucose intolerance, increased visceral fat, weight gain, as well as serum glucose, triacylglycerol, total cholesterol and LDL cholesterol; however, E. uniflora prevented these alterations. 28618655 1 52 from effect 188:193 arg1 status 253:258 metabolic status 243:258 metabolic status 243:258 The aim of this study was to investigate the effect of Eugenia uniflora fruit (red type) extract on metabolic status, as well as on neurochemical and behavioral parameters in an animal model of metabolic syndrome induced by a highly palatable diet (HPD). 28618655 1 52 from effect 188:193 arg1 parameters 304:313 neurochemical and behavioral parameters 275:313 neurochemical and behavioral parameters in an animal model of metabolic syndrome induced by a highly palatable diet (HPD) 275:395 The aim of this study was to investigate the effect of Eugenia uniflora fruit (red type) extract on metabolic status, as well as on neurochemical and behavioral parameters in an animal model of metabolic syndrome induced by a highly palatable diet (HPD). 28618655 0 53 theme standardized 34:45 arg1 extract 47:53 Eugenia uniflora fruit (red type) standardized extract 0:53 Eugenia uniflora fruit (red type) standardized extract: a potential pharmacological tool to diet-induced metabolic syndrome damage management. 0:141 Eugenia uniflora fruit (red type) standardized extract: a potential pharmacological tool to diet-induced metabolic syndrome damage management. 28618655 5 54 theme HPD-induced 1027:1037 arg1 reduction 1039:1047 a HPD-induced reduction 1025:1047 a HPD-induced reduction of thiol content in these cerebral structures 1025:1093 We observed a HPD-induced reduction of thiol content in these cerebral structures. 28618655 2 55 dep SC 505:506 arg1 extract 524:530 uniflora extract 515:530 uniflora extract 515:530 Rats were treated for 150days and divided into 4 experimental groups: standard chow (SC) and water orally, SC and E. uniflora extract (200mg/kg daily, p.o), HPD and water orally, HPD and extract. 28618655 6 56 from HPD 1193:1195 arg1 time 1228:1231 immobility time 1217:1231 immobility time observed in the forced swim test 1217:1264 The extract prevented increased acetylcholinesterase activity in the prefrontal cortex caused by HPD and the increase in immobility time observed in the forced swim test. 28618655 6 57 theme increased 1118:1126 arg1 activity 1149:1156 increased acetylcholinesterase activity 1118:1156 increased acetylcholinesterase activity in the prefrontal cortex caused by HPD and the increase in immobility time observed in the forced swim test 1118:1264 The extract prevented increased acetylcholinesterase activity in the prefrontal cortex caused by HPD and the increase in immobility time observed in the forced swim test. 28618655 3 58 theme serum 695:699 arg1 glucose 701:707 serum glucose 695:707 serum glucose 695:707 Our data showed that HPD caused glucose intolerance, increased visceral fat, weight gain, as well as serum glucose, triacylglycerol, total cholesterol and LDL cholesterol; however, E. uniflora prevented these alterations. 28618655 3 58 theme serum 695:699 arg1 intolerance 634:644 glucose intolerance 626:644 glucose intolerance 626:644 Our data showed that HPD caused glucose intolerance, increased visceral fat, weight gain, as well as serum glucose, triacylglycerol, total cholesterol and LDL cholesterol; however, E. uniflora prevented these alterations. 28618655 3 59 theme glucose 626:632 arg1 fat 666:668 increased visceral fat 647:668 increased visceral fat 647:668 Our data showed that HPD caused glucose intolerance, increased visceral fat, weight gain, as well as serum glucose, triacylglycerol, total cholesterol and LDL cholesterol; however, E. uniflora prevented these alterations. 28618655 3 59 theme glucose 626:632 arg1 cholesterol 733:743 total cholesterol 727:743 total cholesterol 727:743 Our data showed that HPD caused glucose intolerance, increased visceral fat, weight gain, as well as serum glucose, triacylglycerol, total cholesterol and LDL cholesterol; however, E. uniflora prevented these alterations. 28618655 3 59 theme glucose 626:632 arg1 glucose 701:707 serum glucose 695:707 serum glucose 695:707 Our data showed that HPD caused glucose intolerance, increased visceral fat, weight gain, as well as serum glucose, triacylglycerol, total cholesterol and LDL cholesterol; however, E. uniflora prevented these alterations. 28618655 3 59 theme glucose 626:632 arg1 intolerance 634:644 glucose intolerance 626:644 glucose intolerance 626:644 Our data showed that HPD caused glucose intolerance, increased visceral fat, weight gain, as well as serum glucose, triacylglycerol, total cholesterol and LDL cholesterol; however, E. uniflora prevented these alterations. 28618655 3 59 theme glucose 626:632 arg1 gain 678:681 weight gain 671:681 weight gain 671:681 Our data showed that HPD caused glucose intolerance, increased visceral fat, weight gain, as well as serum glucose, triacylglycerol, total cholesterol and LDL cholesterol; however, E. uniflora prevented these alterations. 28618655 3 59 theme glucose 626:632 arg1 cholesterol 753:763 LDL cholesterol 749:763 LDL cholesterol 749:763 Our data showed that HPD caused glucose intolerance, increased visceral fat, weight gain, as well as serum glucose, triacylglycerol, total cholesterol and LDL cholesterol; however, E. uniflora prevented these alterations. 28618655 3 59 theme glucose 626:632 arg1 triacylglycerol 710:724 triacylglycerol 710:724 triacylglycerol 710:724 Our data showed that HPD caused glucose intolerance, increased visceral fat, weight gain, as well as serum glucose, triacylglycerol, total cholesterol and LDL cholesterol; however, E. uniflora prevented these alterations. 28618655 4 60 theme lipid 838:842 arg1 peroxidation 844:855 lipid peroxidation 838:855 lipid peroxidation 838:855 The extract decreased lipid peroxidation and prevented the reduction of superoxide dismutase and catalase activities in the prefrontal cortex, hippocampus and striatum of animals submitted to HPD. 28618655 1 61 theme Eugenia 198:204 arg1 extract 232:238 Eugenia uniflora fruit (red type) extract 198:238 Eugenia uniflora fruit (red type) extract 198:238 The aim of this study was to investigate the effect of Eugenia uniflora fruit (red type) extract on metabolic status, as well as on neurochemical and behavioral parameters in an animal model of metabolic syndrome induced by a highly palatable diet (HPD). 28618655 7 62 theme LC/MS 1299:1303 arg1 analysis 1305:1312 LC/MS analysis 1299:1312 LC/MS analysis 1299:1312 Regarding chemical composition, LC/MS analysis showed the presence of nine anthocyanins as the major compounds. 28618655 4 63 theme dismutase 899:907 arg1 activities 922:931 superoxide dismutase and catalase activities 888:931 superoxide dismutase and catalase activities 888:931 The extract decreased lipid peroxidation and prevented the reduction of superoxide dismutase and catalase activities in the prefrontal cortex, hippocampus and striatum of animals submitted to HPD. 28618655 1 64 theme uniflora 206:213 arg1 extract 232:238 Eugenia uniflora fruit (red type) extract 198:238 Eugenia uniflora fruit (red type) extract 198:238 The aim of this study was to investigate the effect of Eugenia uniflora fruit (red type) extract on metabolic status, as well as on neurochemical and behavioral parameters in an animal model of metabolic syndrome induced by a highly palatable diet (HPD). 28618655 1 65 theme palatable 376:384 arg1 HPD 392:394 HPD 392:394 HPD 392:394 The aim of this study was to investigate the effect of Eugenia uniflora fruit (red type) extract on metabolic status, as well as on neurochemical and behavioral parameters in an animal model of metabolic syndrome induced by a highly palatable diet (HPD). 28618655 1 65 theme palatable 376:384 arg1 diet 386:389 a highly palatable diet 367:389 a highly palatable diet (HPD) 367:395 The aim of this study was to investigate the effect of Eugenia uniflora fruit (red type) extract on metabolic status, as well as on neurochemical and behavioral parameters in an animal model of metabolic syndrome induced by a highly palatable diet (HPD). 28618655 4 66 theme prefrontal 940:949 arg1 cortex 951:956 the prefrontal cortex 936:956 the prefrontal cortex 936:956 The extract decreased lipid peroxidation and prevented the reduction of superoxide dismutase and catalase activities in the prefrontal cortex, hippocampus and striatum of animals submitted to HPD. 28618655 1 67 theme fruit 215:219 arg1 extract 232:238 Eugenia uniflora fruit (red type) extract 198:238 Eugenia uniflora fruit (red type) extract 198:238 The aim of this study was to investigate the effect of Eugenia uniflora fruit (red type) extract on metabolic status, as well as on neurochemical and behavioral parameters in an animal model of metabolic syndrome induced by a highly palatable diet (HPD). 28618655 6 68 theme swim 1256:1259 arg1 test 1261:1264 the forced swim test 1245:1264 the forced swim test 1245:1264 The extract prevented increased acetylcholinesterase activity in the prefrontal cortex caused by HPD and the increase in immobility time observed in the forced swim test. 28618655 1 69 theme neurochemical 275:287 arg1 parameters 304:313 neurochemical and behavioral parameters 275:313 neurochemical and behavioral parameters in an animal model of metabolic syndrome induced by a highly palatable diet (HPD) 275:395 The aim of this study was to investigate the effect of Eugenia uniflora fruit (red type) extract on metabolic status, as well as on neurochemical and behavioral parameters in an animal model of metabolic syndrome induced by a highly palatable diet (HPD). 28618655 3 70 theme visceral 657:664 arg1 fat 666:668 increased visceral fat 647:668 increased visceral fat 647:668 Our data showed that HPD caused glucose intolerance, increased visceral fat, weight gain, as well as serum glucose, triacylglycerol, total cholesterol and LDL cholesterol; however, E. uniflora prevented these alterations. 28618655 3 70 theme visceral 657:664 arg1 intolerance 634:644 glucose intolerance 626:644 glucose intolerance 626:644 Our data showed that HPD caused glucose intolerance, increased visceral fat, weight gain, as well as serum glucose, triacylglycerol, total cholesterol and LDL cholesterol; however, E. uniflora prevented these alterations. 28618655 5 71 theme cerebral 1075:1082 arg1 structures 1084:1093 these cerebral structures 1069:1093 these cerebral structures 1069:1093 We observed a HPD-induced reduction of thiol content in these cerebral structures. 28618655 8 72 theme antidepressant-like 1512:1530 arg1 effects 1532:1538 antioxidant and antidepressant-like effects 1496:1538 antioxidant and antidepressant-like effects 1496:1538 In conclusion, E. uniflora extract showed benefits against metabolic alterations caused by HPD, as well as exhibited antioxidant and antidepressant-like effects. 28618655 2 73 theme experimental 447:458 arg1 SC 505:506 SC 505:506 SC 505:506 Rats were treated for 150days and divided into 4 experimental groups: standard chow (SC) and water orally, SC and E. uniflora extract (200mg/kg daily, p.o), HPD and water orally, HPD and extract. 28618655 2 73 theme experimental 447:458 arg1 extract 585:591 extract 585:591 extract 585:591 Rats were treated for 150days and divided into 4 experimental groups: standard chow (SC) and water orally, SC and E. uniflora extract (200mg/kg daily, p.o), HPD and water orally, HPD and extract. 28618655 2 73 theme experimental 447:458 arg1 groups 460:465 4 experimental groups 445:465 4 experimental groups: standard chow (SC) and water orally, SC and E. uniflora extract (200mg/kg daily, p.o), HPD and water orally, HPD and extract 445:591 Rats were treated for 150days and divided into 4 experimental groups: standard chow (SC) and water orally, SC and E. uniflora extract (200mg/kg daily, p.o), HPD and water orally, HPD and extract. 28618655 2 73 theme experimental 447:458 arg1 water 563:567 water 563:567 water 563:567 Rats were treated for 150days and divided into 4 experimental groups: standard chow (SC) and water orally, SC and E. uniflora extract (200mg/kg daily, p.o), HPD and water orally, HPD and extract. 28618655 2 73 theme experimental 447:458 arg1 E. 512:513 E. 512:513 E. 512:513 Rats were treated for 150days and divided into 4 experimental groups: standard chow (SC) and water orally, SC and E. uniflora extract (200mg/kg daily, p.o), HPD and water orally, HPD and extract. 28618655 2 73 theme experimental 447:458 arg1 water 491:495 water 491:495 water 491:495 Rats were treated for 150days and divided into 4 experimental groups: standard chow (SC) and water orally, SC and E. uniflora extract (200mg/kg daily, p.o), HPD and water orally, HPD and extract. 28618655 2 73 theme experimental 447:458 arg1 HPD 577:579 HPD 577:579 HPD 577:579 Rats were treated for 150days and divided into 4 experimental groups: standard chow (SC) and water orally, SC and E. uniflora extract (200mg/kg daily, p.o), HPD and water orally, HPD and extract. 28618655 2 73 theme experimental 447:458 arg1 chow 477:480 standard chow 468:480 standard chow (SC) 468:485 Rats were treated for 150days and divided into 4 experimental groups: standard chow (SC) and water orally, SC and E. uniflora extract (200mg/kg daily, p.o), HPD and water orally, HPD and extract. 28618655 2 73 theme experimental 447:458 arg1 HPD 555:557 HPD 555:557 HPD 555:557 Rats were treated for 150days and divided into 4 experimental groups: standard chow (SC) and water orally, SC and E. uniflora extract (200mg/kg daily, p.o), HPD and water orally, HPD and extract. 28856812 0 0 from VtgC 148:151 arg1 fishes 172:177 chondrichthyean fishes 156:177 chondrichthyean fishes 156:177 Resolving the complexity of vitellogenins and their receptors in the tetraploid Atlantic salmon (Salmo salar): Ancient origin of the phosvitin-less VtgC in chondrichthyean fishes. 28856812 3 1 from repertoire 624:633 arg1 salmon 680:685 the tetraploid Atlantic salmon 656:685 the tetraploid Atlantic salmon (Salmo salar) 656:699 Here, we clarify the evolutionary history of vertebrate Vtgs, including the teleost VtgC, which lacks phosvitin, and investigate the repertoire of Vtgs and VtgRs in the tetraploid Atlantic salmon (Salmo salar). 28856812 3 1 from repertoire 624:633 arg1 salar 694:698 Salmo salar 688:698 Salmo salar 688:698 Here, we clarify the evolutionary history of vertebrate Vtgs, including the teleost VtgC, which lacks phosvitin, and investigate the repertoire of Vtgs and VtgRs in the tetraploid Atlantic salmon (Salmo salar). 28856812 1 2 from development 288:298 arg1 organisms 313:321 oviparous organisms 303:321 oviparous organisms 303:321 Egg yolk proteins are mainly derived from vitellogenin (Vtg), and serve as essential nutrients during early development in oviparous organisms. 28856812 2 3 theme Vertebrate 324:333 arg1 Vtgs 335:338 Vertebrate Vtgs 324:338 Vertebrate Vtgs 324:338 Vertebrate Vtgs are predominantly synthesized in the liver of maturing females, and are internalized by the oocyte after binding to specific surface receptors (VtgR). 28856812 4 4 theme vtg 804:806 arg1 present 825:831 present 825:831 present 825:831 Conserved synteny of the vtg genes in elephant fish (Callorhinchus milii) strongly indicates that the vtg gene cluster was present in the ancestor of tetrapods and ray-finned fish. 28856812 4 4 theme vtg 804:806 arg1 cluster 813:819 the vtg gene cluster 800:819 the vtg gene cluster 800:819 Conserved synteny of the vtg genes in elephant fish (Callorhinchus milii) strongly indicates that the vtg gene cluster was present in the ancestor of tetrapods and ray-finned fish. 28856812 10 5 theme previtellogenic 1718:1732 arg1 oocytes 1734:1740 the previtellogenic oocytes 1714:1740 the previtellogenic oocytes 1714:1740 Strongly increased vtgAsa1 expression during vitellogenesis contrasted with the peaks of vtgr1 and vtgr2 in the previtellogenic oocytes, which gradually decreased over the same period. 28856812 6 6 theme tandem-duplicated 1099:1115 arg1 VtgCs 1117:1121 the tandem-duplicated VtgCs 1095:1121 the tandem-duplicated VtgCs 1095:1121 In contrast, the tandem-duplicated VtgCs identified in the spotted gar (Lepisosteus oculatus) both contain the phosvitin domain. 28856812 3 7 theme tetraploid 660:669 arg1 salmon 680:685 the tetraploid Atlantic salmon 656:685 the tetraploid Atlantic salmon (Salmo salar) 656:699 Here, we clarify the evolutionary history of vertebrate Vtgs, including the teleost VtgC, which lacks phosvitin, and investigate the repertoire of Vtgs and VtgRs in the tetraploid Atlantic salmon (Salmo salar). 28856812 3 7 theme tetraploid 660:669 arg1 salar 694:698 Salmo salar 688:698 Salmo salar 688:698 Here, we clarify the evolutionary history of vertebrate Vtgs, including the teleost VtgC, which lacks phosvitin, and investigate the repertoire of Vtgs and VtgRs in the tetraploid Atlantic salmon (Salmo salar). 28856812 9 8 link O-linked 1535:1542 arg1 domain 1550:1555 the O-linked sugar domain 1531:1555 the O-linked sugar domain 1531:1555 The splice variant lacking the O-linked sugar domain dominated ovarian expression of vtgr1 and vtgr2. 28856812 7 9 theme VtgAsb 1327:1332 arg1 proteins 1334:1341 the complete VtgAsa1, phosvitin-less VtgC, and truncated VtgAsb proteins 1270:1341 the complete VtgAsa1, phosvitin-less VtgC, and truncated VtgAsb proteins 1270:1341 The Atlantic salmon genome harbors four vtg genes encoding the complete VtgAsa1, phosvitin-less VtgC, and truncated VtgAsb proteins; vtgAsa2 is a pseudogene. 28856812 3 10 theme Salmo 688:692 arg1 salmon 680:685 the tetraploid Atlantic salmon 656:685 the tetraploid Atlantic salmon (Salmo salar) 656:699 Here, we clarify the evolutionary history of vertebrate Vtgs, including the teleost VtgC, which lacks phosvitin, and investigate the repertoire of Vtgs and VtgRs in the tetraploid Atlantic salmon (Salmo salar). 28856812 3 10 theme Salmo 688:692 arg1 salar 694:698 Salmo salar 688:698 Salmo salar 688:698 Here, we clarify the evolutionary history of vertebrate Vtgs, including the teleost VtgC, which lacks phosvitin, and investigate the repertoire of Vtgs and VtgRs in the tetraploid Atlantic salmon (Salmo salar). 28856812 10 11 theme vtgr2 1705:1709 arg1 peaks 1686:1690 the peaks 1682:1690 the peaks of vtgr1 and vtgr2 in the previtellogenic oocytes, which gradually decreased over the same period 1682:1788 Strongly increased vtgAsa1 expression during vitellogenesis contrasted with the peaks of vtgr1 and vtgr2 in the previtellogenic oocytes, which gradually decreased over the same period. 28856812 6 12 theme spotted 1141:1147 arg1 gar 1149:1151 the spotted gar 1137:1151 the spotted gar (Lepisosteus oculatus) 1137:1174 In contrast, the tandem-duplicated VtgCs identified in the spotted gar (Lepisosteus oculatus) both contain the phosvitin domain. 28856812 5 13 theme early 980:984 arg1 events 997:1002 early truncation events 980:1002 early truncation events that eventually allowed the total disappearance of phosvitin in teleost VtgC 980:1079 The shortened phosvitin in the VtgC ortholog of this chondrichthyean fish may have resulted from early truncation events that eventually allowed the total disappearance of phosvitin in teleost VtgC. 28856812 3 14 theme evolutionary 512:523 arg1 history 525:531 the evolutionary history 508:531 the evolutionary history of vertebrate Vtgs, including the teleost VtgC, which lacks phosvitin 508:601 Here, we clarify the evolutionary history of vertebrate Vtgs, including the teleost VtgC, which lacks phosvitin, and investigate the repertoire of Vtgs and VtgRs in the tetraploid Atlantic salmon (Salmo salar). 28856812 1 15 theme yolk 184:187 arg1 proteins 189:196 Egg yolk proteins 180:196 Egg yolk proteins 180:196 Egg yolk proteins are mainly derived from vitellogenin (Vtg), and serve as essential nutrients during early development in oviparous organisms. 28856812 1 15 theme yolk 184:187 arg1 nutrients 265:273 essential nutrients 255:273 essential nutrients 255:273 Egg yolk proteins are mainly derived from vitellogenin (Vtg), and serve as essential nutrients during early development in oviparous organisms. 28856812 7 16 theme VtgC 1307:1310 arg1 proteins 1334:1341 the complete VtgAsa1, phosvitin-less VtgC, and truncated VtgAsb proteins 1270:1341 the complete VtgAsa1, phosvitin-less VtgC, and truncated VtgAsb proteins 1270:1341 The Atlantic salmon genome harbors four vtg genes encoding the complete VtgAsa1, phosvitin-less VtgC, and truncated VtgAsb proteins; vtgAsa2 is a pseudogene. 28856812 4 17 located present 825:831 arg2 present 825:831 present 825:831 present 825:831 Conserved synteny of the vtg genes in elephant fish (Callorhinchus milii) strongly indicates that the vtg gene cluster was present in the ancestor of tetrapods and ray-finned fish. 28856812 4 17 located present 825:831 arg1 ancestor 840:847 the ancestor 836:847 the ancestor of tetrapods and ray-finned fish 836:880 Conserved synteny of the vtg genes in elephant fish (Callorhinchus milii) strongly indicates that the vtg gene cluster was present in the ancestor of tetrapods and ray-finned fish. 28856812 4 17 located present 825:831 arg2 cluster 813:819 the vtg gene cluster 800:819 the vtg gene cluster 800:819 Conserved synteny of the vtg genes in elephant fish (Callorhinchus milii) strongly indicates that the vtg gene cluster was present in the ancestor of tetrapods and ray-finned fish. 28856812 0 18 theme Ancient 111:117 arg1 origin 119:124 Ancient origin 111:124 Ancient origin of the phosvitin-less VtgC in chondrichthyean fishes 111:177 Resolving the complexity of vitellogenins and their receptors in the tetraploid Atlantic salmon (Salmo salar): Ancient origin of the phosvitin-less VtgC in chondrichthyean fishes. 28856812 6 19 dep identified 1123:1132 arg1 both 1176:1179 both 1176:1179 both 1176:1179 In contrast, the tandem-duplicated VtgCs identified in the spotted gar (Lepisosteus oculatus) both contain the phosvitin domain. 28856812 4 20 from present 825:831 arg1 ancestor 840:847 the ancestor 836:847 the ancestor of tetrapods and ray-finned fish 836:880 Conserved synteny of the vtg genes in elephant fish (Callorhinchus milii) strongly indicates that the vtg gene cluster was present in the ancestor of tetrapods and ray-finned fish. 28856812 3 21 theme Vtgs 547:550 arg1 history 525:531 the evolutionary history 508:531 the evolutionary history of vertebrate Vtgs, including the teleost VtgC, which lacks phosvitin 508:601 Here, we clarify the evolutionary history of vertebrate Vtgs, including the teleost VtgC, which lacks phosvitin, and investigate the repertoire of Vtgs and VtgRs in the tetraploid Atlantic salmon (Salmo salar). 28856812 9 22 theme ovarian 1567:1573 arg1 expression 1575:1584 ovarian expression 1567:1584 ovarian expression of vtgr1 and vtgr2 1567:1603 The splice variant lacking the O-linked sugar domain dominated ovarian expression of vtgr1 and vtgr2. 28856812 8 23 theme vtg 1379:1381 arg1 genes 1383:1387 The three vtg genes 1369:1387 The three vtg genes 1369:1387 The three vtg genes were mainly expressed in the liver of maturing females, and the vtgAsa1 transcript predominated prior to spawning. 28856812 7 24 theme complete 1274:1281 arg1 VtgAsa1 1283:1289 complete VtgAsa1 1274:1289 complete VtgAsa1 1274:1289 The Atlantic salmon genome harbors four vtg genes encoding the complete VtgAsa1, phosvitin-less VtgC, and truncated VtgAsb proteins; vtgAsa2 is a pseudogene. 28856812 0 25 theme phosvitin-less 133:146 arg1 VtgC 148:151 the phosvitin-less VtgC 129:151 the phosvitin-less VtgC in chondrichthyean fishes 129:177 Resolving the complexity of vitellogenins and their receptors in the tetraploid Atlantic salmon (Salmo salar): Ancient origin of the phosvitin-less VtgC in chondrichthyean fishes. 28856812 6 26 dep gar 1149:1151 arg1 oculatus 1166:1173 Lepisosteus oculatus 1154:1173 Lepisosteus oculatus 1154:1173 In contrast, the tandem-duplicated VtgCs identified in the spotted gar (Lepisosteus oculatus) both contain the phosvitin domain. 28856812 3 27 theme teleost 567:573 arg1 VtgC 575:578 the teleost VtgC 563:578 the teleost VtgC 563:578 Here, we clarify the evolutionary history of vertebrate Vtgs, including the teleost VtgC, which lacks phosvitin, and investigate the repertoire of Vtgs and VtgRs in the tetraploid Atlantic salmon (Salmo salar). 28856812 2 28 theme specific 456:463 arg1 VtgR 484:487 VtgR 484:487 VtgR 484:487 Vertebrate Vtgs are predominantly synthesized in the liver of maturing females, and are internalized by the oocyte after binding to specific surface receptors (VtgR). 28856812 2 28 theme specific 456:463 arg1 receptors 473:481 specific surface receptors 456:481 specific surface receptors (VtgR) 456:488 Vertebrate Vtgs are predominantly synthesized in the liver of maturing females, and are internalized by the oocyte after binding to specific surface receptors (VtgR). 28856812 0 29 theme tetraploid 69:78 arg1 salmon 89:94 the tetraploid Atlantic salmon 65:94 the tetraploid Atlantic salmon (Salmo salar) 65:108 Resolving the complexity of vitellogenins and their receptors in the tetraploid Atlantic salmon (Salmo salar): Ancient origin of the phosvitin-less VtgC in chondrichthyean fishes. 28856812 0 29 theme tetraploid 69:78 arg1 salar 103:107 Salmo salar 97:107 Salmo salar 97:107 Resolving the complexity of vitellogenins and their receptors in the tetraploid Atlantic salmon (Salmo salar): Ancient origin of the phosvitin-less VtgC in chondrichthyean fishes. 28856812 5 30 theme phosvitin 1055:1063 arg1 disappearance 1038:1050 the total disappearance 1028:1050 the total disappearance of phosvitin in teleost VtgC 1028:1079 The shortened phosvitin in the VtgC ortholog of this chondrichthyean fish may have resulted from early truncation events that eventually allowed the total disappearance of phosvitin in teleost VtgC. 28856812 4 31 from synteny 712:718 arg1 fish 749:752 elephant fish 740:752 elephant fish (Callorhinchus milii) 740:774 Conserved synteny of the vtg genes in elephant fish (Callorhinchus milii) strongly indicates that the vtg gene cluster was present in the ancestor of tetrapods and ray-finned fish. 28856812 4 32 theme fish 877:880 arg1 ancestor 840:847 the ancestor 836:847 the ancestor of tetrapods and ray-finned fish 836:880 Conserved synteny of the vtg genes in elephant fish (Callorhinchus milii) strongly indicates that the vtg gene cluster was present in the ancestor of tetrapods and ray-finned fish. 28856812 11 33 theme receptor 1860:1867 arg1 number 1869:1874 receptor number 1860:1874 receptor number 1860:1874 Recycling of the oocyte VtgRs is probably not sufficient to maintain receptor number during vitellogenesis. 28856812 0 34 theme Salmo 97:101 arg1 salmon 89:94 the tetraploid Atlantic salmon 65:94 the tetraploid Atlantic salmon (Salmo salar) 65:108 Resolving the complexity of vitellogenins and their receptors in the tetraploid Atlantic salmon (Salmo salar): Ancient origin of the phosvitin-less VtgC in chondrichthyean fishes. 28856812 0 34 theme Salmo 97:101 arg1 salar 103:107 Salmo salar 97:107 Salmo salar 97:107 Resolving the complexity of vitellogenins and their receptors in the tetraploid Atlantic salmon (Salmo salar): Ancient origin of the phosvitin-less VtgC in chondrichthyean fishes. 28856812 8 35 theme females 1436:1442 arg1 liver 1418:1422 the liver 1414:1422 the liver of maturing females 1414:1442 The three vtg genes were mainly expressed in the liver of maturing females, and the vtgAsa1 transcript predominated prior to spawning. 28856812 11 36 theme VtgRs 1815:1819 arg1 Recycling 1791:1799 Recycling 1791:1799 Recycling of the oocyte VtgRs 1791:1819 Recycling of the oocyte VtgRs is probably not sufficient to maintain receptor number during vitellogenesis. 28856812 0 37 from fishes 172:177 arg1 origin 119:124 Ancient origin 111:124 Ancient origin of the phosvitin-less VtgC in chondrichthyean fishes 111:177 Resolving the complexity of vitellogenins and their receptors in the tetraploid Atlantic salmon (Salmo salar): Ancient origin of the phosvitin-less VtgC in chondrichthyean fishes. 28856812 8 38 theme vtgAsa1 1453:1459 arg1 transcript 1461:1470 the vtgAsa1 transcript 1449:1470 the vtgAsa1 transcript 1449:1470 The three vtg genes were mainly expressed in the liver of maturing females, and the vtgAsa1 transcript predominated prior to spawning. 28856812 4 39 theme elephant 740:747 arg1 fish 749:752 elephant fish 740:752 elephant fish (Callorhinchus milii) 740:774 Conserved synteny of the vtg genes in elephant fish (Callorhinchus milii) strongly indicates that the vtg gene cluster was present in the ancestor of tetrapods and ray-finned fish. 28856812 2 40 theme maturing 386:393 arg1 females 395:401 maturing females 386:401 maturing females 386:401 Vertebrate Vtgs are predominantly synthesized in the liver of maturing females, and are internalized by the oocyte after binding to specific surface receptors (VtgR). 28856812 0 41 theme vitellogenins 28:40 arg1 complexity 14:23 the complexity 10:23 the complexity of vitellogenins and their receptors 10:60 Resolving the complexity of vitellogenins and their receptors in the tetraploid Atlantic salmon (Salmo salar): Ancient origin of the phosvitin-less VtgC in chondrichthyean fishes. 28856812 5 42 theme teleost 1068:1074 arg1 VtgC 1076:1079 teleost VtgC 1068:1079 teleost VtgC 1068:1079 The shortened phosvitin in the VtgC ortholog of this chondrichthyean fish may have resulted from early truncation events that eventually allowed the total disappearance of phosvitin in teleost VtgC. 28856812 7 43 theme Atlantic 1215:1222 arg1 genome 1231:1236 The Atlantic salmon genome 1211:1236 The Atlantic salmon genome 1211:1236 The Atlantic salmon genome harbors four vtg genes encoding the complete VtgAsa1, phosvitin-less VtgC, and truncated VtgAsb proteins; vtgAsa2 is a pseudogene. 28856812 10 44 theme vtgAsa1 1625:1631 arg1 expression 1633:1642 Strongly increased vtgAsa1 expression 1606:1642 Strongly increased vtgAsa1 expression during vitellogenesis 1606:1664 Strongly increased vtgAsa1 expression during vitellogenesis contrasted with the peaks of vtgr1 and vtgr2 in the previtellogenic oocytes, which gradually decreased over the same period. 28856812 1 45 theme early 282:286 arg1 development 288:298 early development 282:298 early development in oviparous organisms 282:321 Egg yolk proteins are mainly derived from vitellogenin (Vtg), and serve as essential nutrients during early development in oviparous organisms. 28856812 5 46 theme fish 952:955 arg1 ortholog 919:926 the VtgC ortholog 910:926 the VtgC ortholog of this chondrichthyean fish 910:955 The shortened phosvitin in the VtgC ortholog of this chondrichthyean fish may have resulted from early truncation events that eventually allowed the total disappearance of phosvitin in teleost VtgC. 28856812 4 47 theme genes 731:735 arg1 synteny 712:718 Conserved synteny 702:718 Conserved synteny of the vtg genes in elephant fish (Callorhinchus milii) 702:774 Conserved synteny of the vtg genes in elephant fish (Callorhinchus milii) strongly indicates that the vtg gene cluster was present in the ancestor of tetrapods and ray-finned fish. 28856812 0 48 theme receptors 52:60 arg1 complexity 14:23 the complexity 10:23 the complexity of vitellogenins and their receptors 10:60 Resolving the complexity of vitellogenins and their receptors in the tetraploid Atlantic salmon (Salmo salar): Ancient origin of the phosvitin-less VtgC in chondrichthyean fishes. 28856812 9 49 theme sugar 1544:1548 arg1 domain 1550:1555 the O-linked sugar domain 1531:1555 the O-linked sugar domain 1531:1555 The splice variant lacking the O-linked sugar domain dominated ovarian expression of vtgr1 and vtgr2. 28856812 3 50 theme VtgRs 647:651 arg1 VtgRs 647:651 VtgRs 647:651 VtgRs 647:651 Here, we clarify the evolutionary history of vertebrate Vtgs, including the teleost VtgC, which lacks phosvitin, and investigate the repertoire of Vtgs and VtgRs in the tetraploid Atlantic salmon (Salmo salar). 28856812 3 50 theme VtgRs 647:651 arg1 Vtgs 638:641 Vtgs 638:641 Vtgs 638:641 Here, we clarify the evolutionary history of vertebrate Vtgs, including the teleost VtgC, which lacks phosvitin, and investigate the repertoire of Vtgs and VtgRs in the tetraploid Atlantic salmon (Salmo salar). 28856812 3 50 theme VtgRs 647:651 arg1 repertoire 624:633 the repertoire 620:633 the repertoire of Vtgs and VtgRs in the tetraploid Atlantic salmon (Salmo salar) 620:699 Here, we clarify the evolutionary history of vertebrate Vtgs, including the teleost VtgC, which lacks phosvitin, and investigate the repertoire of Vtgs and VtgRs in the tetraploid Atlantic salmon (Salmo salar). 28856812 0 51 theme chondrichthyean 156:170 arg1 fishes 172:177 chondrichthyean fishes 156:177 chondrichthyean fishes 156:177 Resolving the complexity of vitellogenins and their receptors in the tetraploid Atlantic salmon (Salmo salar): Ancient origin of the phosvitin-less VtgC in chondrichthyean fishes. 28856812 5 52 from phosvitin 897:905 arg1 ortholog 919:926 the VtgC ortholog 910:926 the VtgC ortholog of this chondrichthyean fish 910:955 The shortened phosvitin in the VtgC ortholog of this chondrichthyean fish may have resulted from early truncation events that eventually allowed the total disappearance of phosvitin in teleost VtgC. 28856812 3 53 theme Vtgs 638:641 arg1 VtgRs 647:651 VtgRs 647:651 VtgRs 647:651 Here, we clarify the evolutionary history of vertebrate Vtgs, including the teleost VtgC, which lacks phosvitin, and investigate the repertoire of Vtgs and VtgRs in the tetraploid Atlantic salmon (Salmo salar). 28856812 3 53 theme Vtgs 638:641 arg1 Vtgs 638:641 Vtgs 638:641 Vtgs 638:641 Here, we clarify the evolutionary history of vertebrate Vtgs, including the teleost VtgC, which lacks phosvitin, and investigate the repertoire of Vtgs and VtgRs in the tetraploid Atlantic salmon (Salmo salar). 28856812 3 53 theme Vtgs 638:641 arg1 repertoire 624:633 the repertoire 620:633 the repertoire of Vtgs and VtgRs in the tetraploid Atlantic salmon (Salmo salar) 620:699 Here, we clarify the evolutionary history of vertebrate Vtgs, including the teleost VtgC, which lacks phosvitin, and investigate the repertoire of Vtgs and VtgRs in the tetraploid Atlantic salmon (Salmo salar). 28856812 6 54 theme phosvitin 1193:1201 arg1 domain 1203:1208 the phosvitin domain 1189:1208 the phosvitin domain 1189:1208 In contrast, the tandem-duplicated VtgCs identified in the spotted gar (Lepisosteus oculatus) both contain the phosvitin domain. 28856812 9 55 theme splice 1508:1513 arg1 variant 1515:1521 The splice variant 1504:1521 The splice variant lacking the O-linked sugar domain 1504:1555 The splice variant lacking the O-linked sugar domain dominated ovarian expression of vtgr1 and vtgr2. 28856812 3 56 theme Atlantic 671:678 arg1 salmon 680:685 the tetraploid Atlantic salmon 656:685 the tetraploid Atlantic salmon (Salmo salar) 656:699 Here, we clarify the evolutionary history of vertebrate Vtgs, including the teleost VtgC, which lacks phosvitin, and investigate the repertoire of Vtgs and VtgRs in the tetraploid Atlantic salmon (Salmo salar). 28856812 3 56 theme Atlantic 671:678 arg1 salar 694:698 Salmo salar 688:698 Salmo salar 688:698 Here, we clarify the evolutionary history of vertebrate Vtgs, including the teleost VtgC, which lacks phosvitin, and investigate the repertoire of Vtgs and VtgRs in the tetraploid Atlantic salmon (Salmo salar). 28856812 9 57 theme vtgr1 1589:1593 arg1 expression 1575:1584 ovarian expression 1567:1584 ovarian expression of vtgr1 and vtgr2 1567:1603 The splice variant lacking the O-linked sugar domain dominated ovarian expression of vtgr1 and vtgr2. 28856812 9 58 theme vtgr2 1599:1603 arg1 expression 1575:1584 ovarian expression 1567:1584 ovarian expression of vtgr1 and vtgr2 1567:1603 The splice variant lacking the O-linked sugar domain dominated ovarian expression of vtgr1 and vtgr2. 28856812 1 59 theme Egg 180:182 arg1 proteins 189:196 Egg yolk proteins 180:196 Egg yolk proteins 180:196 Egg yolk proteins are mainly derived from vitellogenin (Vtg), and serve as essential nutrients during early development in oviparous organisms. 28856812 1 59 theme Egg 180:182 arg1 nutrients 265:273 essential nutrients 255:273 essential nutrients 255:273 Egg yolk proteins are mainly derived from vitellogenin (Vtg), and serve as essential nutrients during early development in oviparous organisms. 28856812 7 60 theme truncated 1317:1325 arg1 VtgAsb 1327:1332 truncated VtgAsb 1317:1332 truncated VtgAsb 1317:1332 The Atlantic salmon genome harbors four vtg genes encoding the complete VtgAsa1, phosvitin-less VtgC, and truncated VtgAsb proteins; vtgAsa2 is a pseudogene. 28856812 5 61 theme truncation 986:995 arg1 events 997:1002 early truncation events 980:1002 early truncation events that eventually allowed the total disappearance of phosvitin in teleost VtgC 980:1079 The shortened phosvitin in the VtgC ortholog of this chondrichthyean fish may have resulted from early truncation events that eventually allowed the total disappearance of phosvitin in teleost VtgC. 28856812 1 62 attach derived 209:215 arg1 Vtg 236:238 Vtg 236:238 Vtg 236:238 Egg yolk proteins are mainly derived from vitellogenin (Vtg), and serve as essential nutrients during early development in oviparous organisms. 28856812 1 62 attach derived 209:215 arg2 proteins 189:196 Egg yolk proteins 180:196 Egg yolk proteins 180:196 Egg yolk proteins are mainly derived from vitellogenin (Vtg), and serve as essential nutrients during early development in oviparous organisms. 28856812 1 62 attach derived 209:215 arg2 nutrients 265:273 essential nutrients 255:273 essential nutrients 255:273 Egg yolk proteins are mainly derived from vitellogenin (Vtg), and serve as essential nutrients during early development in oviparous organisms. 28856812 1 62 attach derived 209:215 arg1 vitellogenin 222:233 vitellogenin 222:233 vitellogenin (Vtg) 222:239 Egg yolk proteins are mainly derived from vitellogenin (Vtg), and serve as essential nutrients during early development in oviparous organisms. 28856812 3 63 theme vertebrate 536:545 arg1 VtgC 575:578 the teleost VtgC 563:578 the teleost VtgC 563:578 Here, we clarify the evolutionary history of vertebrate Vtgs, including the teleost VtgC, which lacks phosvitin, and investigate the repertoire of Vtgs and VtgRs in the tetraploid Atlantic salmon (Salmo salar). 28856812 3 63 theme vertebrate 536:545 arg1 Vtgs 547:550 vertebrate Vtgs 536:550 vertebrate Vtgs 536:550 Here, we clarify the evolutionary history of vertebrate Vtgs, including the teleost VtgC, which lacks phosvitin, and investigate the repertoire of Vtgs and VtgRs in the tetraploid Atlantic salmon (Salmo salar). 28856812 4 64 theme gene 808:811 arg1 present 825:831 present 825:831 present 825:831 Conserved synteny of the vtg genes in elephant fish (Callorhinchus milii) strongly indicates that the vtg gene cluster was present in the ancestor of tetrapods and ray-finned fish. 28856812 4 64 theme gene 808:811 arg1 cluster 813:819 the vtg gene cluster 800:819 the vtg gene cluster 800:819 Conserved synteny of the vtg genes in elephant fish (Callorhinchus milii) strongly indicates that the vtg gene cluster was present in the ancestor of tetrapods and ray-finned fish. 28856812 7 65 theme phosvitin-less 1292:1305 arg1 VtgC 1307:1310 phosvitin-less VtgC 1292:1310 phosvitin-less VtgC 1292:1310 The Atlantic salmon genome harbors four vtg genes encoding the complete VtgAsa1, phosvitin-less VtgC, and truncated VtgAsb proteins; vtgAsa2 is a pseudogene. 28856812 0 66 theme VtgC 148:151 arg1 origin 119:124 Ancient origin 111:124 Ancient origin of the phosvitin-less VtgC in chondrichthyean fishes 111:177 Resolving the complexity of vitellogenins and their receptors in the tetraploid Atlantic salmon (Salmo salar): Ancient origin of the phosvitin-less VtgC in chondrichthyean fishes. 28856812 7 67 theme VtgAsa1 1283:1289 arg1 proteins 1334:1341 the complete VtgAsa1, phosvitin-less VtgC, and truncated VtgAsb proteins 1270:1341 the complete VtgAsa1, phosvitin-less VtgC, and truncated VtgAsb proteins 1270:1341 The Atlantic salmon genome harbors four vtg genes encoding the complete VtgAsa1, phosvitin-less VtgC, and truncated VtgAsb proteins; vtgAsa2 is a pseudogene. 28856812 10 68 from peaks 1686:1690 arg1 oocytes 1734:1740 the previtellogenic oocytes 1714:1740 the previtellogenic oocytes 1714:1740 Strongly increased vtgAsa1 expression during vitellogenesis contrasted with the peaks of vtgr1 and vtgr2 in the previtellogenic oocytes, which gradually decreased over the same period. 28856812 2 69 theme surface 465:471 arg1 VtgR 484:487 VtgR 484:487 VtgR 484:487 Vertebrate Vtgs are predominantly synthesized in the liver of maturing females, and are internalized by the oocyte after binding to specific surface receptors (VtgR). 28856812 2 69 theme surface 465:471 arg1 receptors 473:481 specific surface receptors 456:481 specific surface receptors (VtgR) 456:488 Vertebrate Vtgs are predominantly synthesized in the liver of maturing females, and are internalized by the oocyte after binding to specific surface receptors (VtgR). 28856812 0 70 theme Atlantic 80:87 arg1 salmon 89:94 the tetraploid Atlantic salmon 65:94 the tetraploid Atlantic salmon (Salmo salar) 65:108 Resolving the complexity of vitellogenins and their receptors in the tetraploid Atlantic salmon (Salmo salar): Ancient origin of the phosvitin-less VtgC in chondrichthyean fishes. 28856812 0 70 theme Atlantic 80:87 arg1 salar 103:107 Salmo salar 97:107 Salmo salar 97:107 Resolving the complexity of vitellogenins and their receptors in the tetraploid Atlantic salmon (Salmo salar): Ancient origin of the phosvitin-less VtgC in chondrichthyean fishes. 28856812 1 71 theme oviparous 303:311 arg1 organisms 313:321 oviparous organisms 303:321 oviparous organisms 303:321 Egg yolk proteins are mainly derived from vitellogenin (Vtg), and serve as essential nutrients during early development in oviparous organisms. 28856812 10 72 theme vtgr1 1695:1699 arg1 peaks 1686:1690 the peaks 1682:1690 the peaks of vtgr1 and vtgr2 in the previtellogenic oocytes, which gradually decreased over the same period 1682:1788 Strongly increased vtgAsa1 expression during vitellogenesis contrasted with the peaks of vtgr1 and vtgr2 in the previtellogenic oocytes, which gradually decreased over the same period. 28856812 4 73 theme tetrapods 852:860 arg1 ancestor 840:847 the ancestor 836:847 the ancestor of tetrapods and ray-finned fish 836:880 Conserved synteny of the vtg genes in elephant fish (Callorhinchus milii) strongly indicates that the vtg gene cluster was present in the ancestor of tetrapods and ray-finned fish. 28856812 8 74 theme maturing 1427:1434 arg1 females 1436:1442 maturing females 1427:1442 maturing females 1427:1442 The three vtg genes were mainly expressed in the liver of maturing females, and the vtgAsa1 transcript predominated prior to spawning. 28856812 4 75 dep fish 749:752 arg1 milii 769:773 Callorhinchus milii 755:773 Callorhinchus milii 755:773 Conserved synteny of the vtg genes in elephant fish (Callorhinchus milii) strongly indicates that the vtg gene cluster was present in the ancestor of tetrapods and ray-finned fish. 28856812 5 76 theme shortened 887:895 arg1 phosvitin 897:905 The shortened phosvitin 883:905 The shortened phosvitin in the VtgC ortholog of this chondrichthyean fish 883:955 The shortened phosvitin in the VtgC ortholog of this chondrichthyean fish may have resulted from early truncation events that eventually allowed the total disappearance of phosvitin in teleost VtgC. 28856812 7 77 theme vtg 1251:1253 arg1 genes 1255:1259 four vtg genes 1246:1259 four vtg genes encoding the complete VtgAsa1, phosvitin-less VtgC, and truncated VtgAsb proteins 1246:1341 The Atlantic salmon genome harbors four vtg genes encoding the complete VtgAsa1, phosvitin-less VtgC, and truncated VtgAsb proteins; vtgAsa2 is a pseudogene. 28856812 4 78 theme ray-finned 866:875 arg1 fish 877:880 ray-finned fish 866:880 ray-finned fish 866:880 Conserved synteny of the vtg genes in elephant fish (Callorhinchus milii) strongly indicates that the vtg gene cluster was present in the ancestor of tetrapods and ray-finned fish. 28856812 4 79 theme Conserved 702:710 arg1 synteny 712:718 Conserved synteny 702:718 Conserved synteny of the vtg genes in elephant fish (Callorhinchus milii) 702:774 Conserved synteny of the vtg genes in elephant fish (Callorhinchus milii) strongly indicates that the vtg gene cluster was present in the ancestor of tetrapods and ray-finned fish. 28856812 5 80 theme total 1032:1036 arg1 disappearance 1038:1050 the total disappearance 1028:1050 the total disappearance of phosvitin in teleost VtgC 1028:1079 The shortened phosvitin in the VtgC ortholog of this chondrichthyean fish may have resulted from early truncation events that eventually allowed the total disappearance of phosvitin in teleost VtgC. 28856812 4 81 from ancestor 840:847 arg1 present 825:831 present 825:831 present 825:831 Conserved synteny of the vtg genes in elephant fish (Callorhinchus milii) strongly indicates that the vtg gene cluster was present in the ancestor of tetrapods and ray-finned fish. 28856812 4 81 from ancestor 840:847 arg1 cluster 813:819 the vtg gene cluster 800:819 the vtg gene cluster 800:819 Conserved synteny of the vtg genes in elephant fish (Callorhinchus milii) strongly indicates that the vtg gene cluster was present in the ancestor of tetrapods and ray-finned fish. 28856812 9 82 theme O-linked 1535:1542 arg1 domain 1550:1555 the O-linked sugar domain 1531:1555 the O-linked sugar domain 1531:1555 The splice variant lacking the O-linked sugar domain dominated ovarian expression of vtgr1 and vtgr2. 28856812 7 83 theme salmon 1224:1229 arg1 genome 1231:1236 The Atlantic salmon genome 1211:1236 The Atlantic salmon genome 1211:1236 The Atlantic salmon genome harbors four vtg genes encoding the complete VtgAsa1, phosvitin-less VtgC, and truncated VtgAsb proteins; vtgAsa2 is a pseudogene. 28856812 2 84 theme females 395:401 arg1 liver 377:381 the liver 373:381 the liver of maturing females 373:401 Vertebrate Vtgs are predominantly synthesized in the liver of maturing females, and are internalized by the oocyte after binding to specific surface receptors (VtgR). 28856812 1 85 theme essential 255:263 arg1 proteins 189:196 Egg yolk proteins 180:196 Egg yolk proteins 180:196 Egg yolk proteins are mainly derived from vitellogenin (Vtg), and serve as essential nutrients during early development in oviparous organisms. 28856812 1 85 theme essential 255:263 arg1 nutrients 265:273 essential nutrients 255:273 essential nutrients 255:273 Egg yolk proteins are mainly derived from vitellogenin (Vtg), and serve as essential nutrients during early development in oviparous organisms. 28856812 4 86 attach present 825:831 arg2 present 825:831 present 825:831 present 825:831 Conserved synteny of the vtg genes in elephant fish (Callorhinchus milii) strongly indicates that the vtg gene cluster was present in the ancestor of tetrapods and ray-finned fish. 28856812 4 86 attach present 825:831 arg1 ancestor 840:847 the ancestor 836:847 the ancestor of tetrapods and ray-finned fish 836:880 Conserved synteny of the vtg genes in elephant fish (Callorhinchus milii) strongly indicates that the vtg gene cluster was present in the ancestor of tetrapods and ray-finned fish. 28856812 4 86 attach present 825:831 arg2 cluster 813:819 the vtg gene cluster 800:819 the vtg gene cluster 800:819 Conserved synteny of the vtg genes in elephant fish (Callorhinchus milii) strongly indicates that the vtg gene cluster was present in the ancestor of tetrapods and ray-finned fish. 28856812 10 87 theme same 1778:1781 arg1 period 1783:1788 the same period 1774:1788 the same period 1774:1788 Strongly increased vtgAsa1 expression during vitellogenesis contrasted with the peaks of vtgr1 and vtgr2 in the previtellogenic oocytes, which gradually decreased over the same period. 28856812 5 88 from disappearance 1038:1050 arg1 VtgC 1076:1079 teleost VtgC 1068:1079 teleost VtgC 1068:1079 The shortened phosvitin in the VtgC ortholog of this chondrichthyean fish may have resulted from early truncation events that eventually allowed the total disappearance of phosvitin in teleost VtgC. 28856812 5 89 theme chondrichthyean 936:950 arg1 fish 952:955 this chondrichthyean fish 931:955 this chondrichthyean fish 931:955 The shortened phosvitin in the VtgC ortholog of this chondrichthyean fish may have resulted from early truncation events that eventually allowed the total disappearance of phosvitin in teleost VtgC. 28856812 10 90 theme increased 1615:1623 arg1 expression 1633:1642 Strongly increased vtgAsa1 expression 1606:1642 Strongly increased vtgAsa1 expression during vitellogenesis 1606:1664 Strongly increased vtgAsa1 expression during vitellogenesis contrasted with the peaks of vtgr1 and vtgr2 in the previtellogenic oocytes, which gradually decreased over the same period. 28856812 0 91 dep Resolving 0:8 arg1 origin 119:124 Ancient origin 111:124 Ancient origin of the phosvitin-less VtgC in chondrichthyean fishes 111:177 Resolving the complexity of vitellogenins and their receptors in the tetraploid Atlantic salmon (Salmo salar): Ancient origin of the phosvitin-less VtgC in chondrichthyean fishes. 28856812 0 92 from origin 119:124 arg1 fishes 172:177 chondrichthyean fishes 156:177 chondrichthyean fishes 156:177 Resolving the complexity of vitellogenins and their receptors in the tetraploid Atlantic salmon (Salmo salar): Ancient origin of the phosvitin-less VtgC in chondrichthyean fishes. 28856812 5 93 theme VtgC 914:917 arg1 ortholog 919:926 the VtgC ortholog 910:926 the VtgC ortholog of this chondrichthyean fish 910:955 The shortened phosvitin in the VtgC ortholog of this chondrichthyean fish may have resulted from early truncation events that eventually allowed the total disappearance of phosvitin in teleost VtgC. 28856812 4 94 theme vtg 727:729 arg1 genes 731:735 the vtg genes 723:735 the vtg genes 723:735 Conserved synteny of the vtg genes in elephant fish (Callorhinchus milii) strongly indicates that the vtg gene cluster was present in the ancestor of tetrapods and ray-finned fish. 28856812 11 95 theme oocyte 1808:1813 arg1 VtgRs 1815:1819 the oocyte VtgRs 1804:1819 the oocyte VtgRs 1804:1819 Recycling of the oocyte VtgRs is probably not sufficient to maintain receptor number during vitellogenesis. 27615797 4 0 theme L1 576:577 arg1 structure 584:592 the L1 loop structure 572:592 the L1 loop structure where two H2A molecules interact in the nucleosome 572:643 The H2AS40Gc site is in the L1 loop structure where two H2A molecules interact in the nucleosome. 27615797 1 1 theme O-GlcNAc 145:152 arg1 modification 155:166 newly discovered O-linked-N-acetylglucosamine (O-GlcNAc) modification 98:166 newly discovered O-linked-N-acetylglucosamine (O-GlcNAc) modification of histone H2A at Ser(40) (H2AS40Gc) 98:203 We report here newly discovered O-linked-N-acetylglucosamine (O-GlcNAc) modification of histone H2A at Ser(40) (H2AS40Gc). 27615797 0 2 from O-GlcNAcylation 6:20 arg1 40 29:30 40 29:30 40 29:30 Novel O-GlcNAcylation on Ser(40) of canonical H2A isoforms specific to viviparity. 27615797 0 2 from O-GlcNAcylation 6:20 arg1 Ser 25:27 Ser 25:27 Ser(40) 25:31 Novel O-GlcNAcylation on Ser(40) of canonical H2A isoforms specific to viviparity. 27615797 3 3 theme RP 412:413 arg1 chromatography 440:453 reverse-phase (RP)-high performance liquid chromatography 397:453 reverse-phase (RP)-high performance liquid chromatography (HPLC) 397:460 The combination of production of monoclonal antibody and mass spectrometric analyses with reverse-phase (RP)-high performance liquid chromatography (HPLC) fractionation indicated that the O-GlcNAcylation is specific to the Ser(40) isoforms. 27615797 3 3 theme RP 412:413 arg1 HPLC 456:459 HPLC 456:459 HPLC 456:459 The combination of production of monoclonal antibody and mass spectrometric analyses with reverse-phase (RP)-high performance liquid chromatography (HPLC) fractionation indicated that the O-GlcNAcylation is specific to the Ser(40) isoforms. 27615797 2 4 theme mouse 210:214 arg1 genome 216:221 The mouse genome 206:221 The mouse genome 206:221 The mouse genome contains 18 H2A isoforms, of which 13 have Ser(40) and the other five have Ala(40). 27615797 5 5 theme stem 782:785 arg1 cells 787:791 mouse trophoblast stem cells 764:791 mouse trophoblast stem cells 764:791 Targets of H2AS40Gc are distributed genome-wide and are dramatically changed during the process of differentiation in mouse trophoblast stem cells. 27615797 6 6 contain possessing 907:916 arg2 isoforms 935:942 only the Ala(40) isoforms 918:942 only the Ala(40) isoforms 918:942 In addition to the mouse, H2AS40Gc was also detected in humans, macaques and cows, whereas non-mammalian species possessing only the Ala(40) isoforms, such as silkworms, zebrafish and Xenopus showed no signal. 27615797 6 6 contain possessing 907:916 arg1 silkworms 953:961 silkworms 953:961 silkworms 953:961 In addition to the mouse, H2AS40Gc was also detected in humans, macaques and cows, whereas non-mammalian species possessing only the Ala(40) isoforms, such as silkworms, zebrafish and Xenopus showed no signal. 27615797 6 6 contain possessing 907:916 arg1 species 899:905 non-mammalian species 885:905 non-mammalian species 885:905 In addition to the mouse, H2AS40Gc was also detected in humans, macaques and cows, whereas non-mammalian species possessing only the Ala(40) isoforms, such as silkworms, zebrafish and Xenopus showed no signal. 27615797 8 7 theme Ser 1163:1165 arg1 emergence 1146:1154 the emergence 1142:1154 the emergence of H2A Ser(40) and its O-GlcNAcylation 1142:1193 We propose that the emergence of H2A Ser(40) and its O-GlcNAcylation linked a genetic event to genome-wide epigenetic events that correlate with the evolution of placental animals. 27615797 2 8 theme H2A 235:237 arg1 isoforms 239:246 18 H2A isoforms 232:246 18 H2A isoforms 232:246 The mouse genome contains 18 H2A isoforms, of which 13 have Ser(40) and the other five have Ala(40). 27615797 1 9 theme discovered 104:113 arg1 modification 155:166 newly discovered O-linked-N-acetylglucosamine (O-GlcNAc) modification 98:166 newly discovered O-linked-N-acetylglucosamine (O-GlcNAc) modification of histone H2A at Ser(40) (H2AS40Gc) 98:203 We report here newly discovered O-linked-N-acetylglucosamine (O-GlcNAc) modification of histone H2A at Ser(40) (H2AS40Gc). 27615797 3 10 theme performance 421:431 arg1 chromatography 440:453 reverse-phase (RP)-high performance liquid chromatography 397:453 reverse-phase (RP)-high performance liquid chromatography (HPLC) 397:460 The combination of production of monoclonal antibody and mass spectrometric analyses with reverse-phase (RP)-high performance liquid chromatography (HPLC) fractionation indicated that the O-GlcNAcylation is specific to the Ser(40) isoforms. 27615797 3 10 theme performance 421:431 arg1 HPLC 456:459 HPLC 456:459 HPLC 456:459 The combination of production of monoclonal antibody and mass spectrometric analyses with reverse-phase (RP)-high performance liquid chromatography (HPLC) fractionation indicated that the O-GlcNAcylation is specific to the Ser(40) isoforms. 27615797 3 11 theme production 326:335 arg1 combination 311:321 The combination 307:321 The combination of production of monoclonal antibody 307:358 The combination of production of monoclonal antibody and mass spectrometric analyses with reverse-phase (RP)-high performance liquid chromatography (HPLC) fractionation indicated that the O-GlcNAcylation is specific to the Ser(40) isoforms. 27615797 3 11 theme production 326:335 arg1 analyses 383:390 mass spectrometric analyses 364:390 mass spectrometric analyses with reverse-phase (RP)-high performance liquid chromatography (HPLC) 364:460 The combination of production of monoclonal antibody and mass spectrometric analyses with reverse-phase (RP)-high performance liquid chromatography (HPLC) fractionation indicated that the O-GlcNAcylation is specific to the Ser(40) isoforms. 27615797 7 12 theme Ser 1042:1044 arg1 isoforms 1050:1057 Ser(40) isoforms 1042:1057 Ser(40) isoforms of H2A 1042:1064 Genome database surveys revealed that Ser(40) isoforms of H2A emerged in Marsupialia and persisted thereafter in mammals. 27615797 3 13 with analyses 383:390 arg1 chromatography 440:453 reverse-phase (RP)-high performance liquid chromatography 397:453 reverse-phase (RP)-high performance liquid chromatography (HPLC) 397:460 The combination of production of monoclonal antibody and mass spectrometric analyses with reverse-phase (RP)-high performance liquid chromatography (HPLC) fractionation indicated that the O-GlcNAcylation is specific to the Ser(40) isoforms. 27615797 3 13 with analyses 383:390 arg1 HPLC 456:459 HPLC 456:459 HPLC 456:459 The combination of production of monoclonal antibody and mass spectrometric analyses with reverse-phase (RP)-high performance liquid chromatography (HPLC) fractionation indicated that the O-GlcNAcylation is specific to the Ser(40) isoforms. 27615797 3 14 theme liquid 433:438 arg1 chromatography 440:453 reverse-phase (RP)-high performance liquid chromatography 397:453 reverse-phase (RP)-high performance liquid chromatography (HPLC) 397:460 The combination of production of monoclonal antibody and mass spectrometric analyses with reverse-phase (RP)-high performance liquid chromatography (HPLC) fractionation indicated that the O-GlcNAcylation is specific to the Ser(40) isoforms. 27615797 3 14 theme liquid 433:438 arg1 HPLC 456:459 HPLC 456:459 HPLC 456:459 The combination of production of monoclonal antibody and mass spectrometric analyses with reverse-phase (RP)-high performance liquid chromatography (HPLC) fractionation indicated that the O-GlcNAcylation is specific to the Ser(40) isoforms. 27615797 5 15 theme differentiation 745:759 arg1 process 734:740 the process 730:740 the process of differentiation in mouse trophoblast stem cells 730:791 Targets of H2AS40Gc are distributed genome-wide and are dramatically changed during the process of differentiation in mouse trophoblast stem cells. 27615797 8 16 theme genome-wide 1221:1231 arg1 events 1244:1249 genome-wide epigenetic events 1221:1249 genome-wide epigenetic events that correlate with the evolution of placental animals 1221:1304 We propose that the emergence of H2A Ser(40) and its O-GlcNAcylation linked a genetic event to genome-wide epigenetic events that correlate with the evolution of placental animals. 27615797 1 17 theme histone 171:177 arg1 H2A 179:181 histone H2A 171:181 histone H2A 171:181 We report here newly discovered O-linked-N-acetylglucosamine (O-GlcNAc) modification of histone H2A at Ser(40) (H2AS40Gc). 27615797 0 18 theme Novel 0:4 arg1 O-GlcNAcylation 6:20 Novel O-GlcNAcylation 0:20 Novel O-GlcNAcylation on Ser(40) of canonical H2A 0:48 Novel O-GlcNAcylation on Ser(40) of canonical H2A isoforms specific to viviparity. 27615797 2 19 contain contains 223:230 arg2 isoforms 239:246 18 H2A isoforms 232:246 18 H2A isoforms 232:246 The mouse genome contains 18 H2A isoforms, of which 13 have Ser(40) and the other five have Ala(40). 27615797 2 19 contain contains 223:230 arg1 genome 216:221 The mouse genome 206:221 The mouse genome 206:221 The mouse genome contains 18 H2A isoforms, of which 13 have Ser(40) and the other five have Ala(40). 27615797 4 20 theme H2A 604:606 arg1 molecules 608:616 two H2A molecules 600:616 two H2A molecules 600:616 The H2AS40Gc site is in the L1 loop structure where two H2A molecules interact in the nucleosome. 27615797 1 21 theme H2A 179:181 arg1 modification 155:166 newly discovered O-linked-N-acetylglucosamine (O-GlcNAc) modification 98:166 newly discovered O-linked-N-acetylglucosamine (O-GlcNAc) modification of histone H2A at Ser(40) (H2AS40Gc) 98:203 We report here newly discovered O-linked-N-acetylglucosamine (O-GlcNAc) modification of histone H2A at Ser(40) (H2AS40Gc). 27615797 7 22 theme Genome 1004:1009 arg1 surveys 1020:1026 Genome database surveys 1004:1026 Genome database surveys 1004:1026 Genome database surveys revealed that Ser(40) isoforms of H2A emerged in Marsupialia and persisted thereafter in mammals. 27615797 8 23 theme genetic 1204:1210 arg1 event 1212:1216 a genetic event 1202:1216 a genetic event 1202:1216 We propose that the emergence of H2A Ser(40) and its O-GlcNAcylation linked a genetic event to genome-wide epigenetic events that correlate with the evolution of placental animals. 27615797 6 24 theme Ala 927:929 arg1 isoforms 935:942 only the Ala(40) isoforms 918:942 only the Ala(40) isoforms 918:942 In addition to the mouse, H2AS40Gc was also detected in humans, macaques and cows, whereas non-mammalian species possessing only the Ala(40) isoforms, such as silkworms, zebrafish and Xenopus showed no signal. 27615797 7 25 theme database 1011:1018 arg1 surveys 1020:1026 Genome database surveys 1004:1026 Genome database surveys 1004:1026 Genome database surveys revealed that Ser(40) isoforms of H2A emerged in Marsupialia and persisted thereafter in mammals. 27615797 6 26 dep mouse 813:817 arg1 addition 797:804 addition 797:804 addition 797:804 In addition to the mouse, H2AS40Gc was also detected in humans, macaques and cows, whereas non-mammalian species possessing only the Ala(40) isoforms, such as silkworms, zebrafish and Xenopus showed no signal. 27615797 8 27 theme O-GlcNAcylation 1179:1193 arg1 emergence 1146:1154 the emergence 1142:1154 the emergence of H2A Ser(40) and its O-GlcNAcylation 1142:1193 We propose that the emergence of H2A Ser(40) and its O-GlcNAcylation linked a genetic event to genome-wide epigenetic events that correlate with the evolution of placental animals. 27615797 3 28 theme mass 364:367 arg1 analyses 383:390 mass spectrometric analyses 364:390 mass spectrometric analyses with reverse-phase (RP)-high performance liquid chromatography (HPLC) 364:460 The combination of production of monoclonal antibody and mass spectrometric analyses with reverse-phase (RP)-high performance liquid chromatography (HPLC) fractionation indicated that the O-GlcNAcylation is specific to the Ser(40) isoforms. 27615797 4 29 theme loop 579:582 arg1 structure 584:592 the L1 loop structure 572:592 the L1 loop structure where two H2A molecules interact in the nucleosome 572:643 The H2AS40Gc site is in the L1 loop structure where two H2A molecules interact in the nucleosome. 27615797 2 30 contain have 293:296 arg1 five 288:291 five 288:291 five 288:291 The mouse genome contains 18 H2A isoforms, of which 13 have Ser(40) and the other five have Ala(40). 27615797 2 30 contain have 293:296 arg2 Ala 298:300 Ala(40) 298:304 Ala(40) 298:304 The mouse genome contains 18 H2A isoforms, of which 13 have Ser(40) and the other five have Ala(40). 27615797 3 31 dep combination 311:321 arg1 fractionation 462:474 fractionation 462:474 fractionation 462:474 The combination of production of monoclonal antibody and mass spectrometric analyses with reverse-phase (RP)-high performance liquid chromatography (HPLC) fractionation indicated that the O-GlcNAcylation is specific to the Ser(40) isoforms. 27615797 4 32 theme H2AS40Gc 552:559 arg1 site 561:564 The H2AS40Gc site 548:564 The H2AS40Gc site 548:564 The H2AS40Gc site is in the L1 loop structure where two H2A molecules interact in the nucleosome. 27615797 3 33 theme monoclonal 340:349 arg1 antibody 351:358 monoclonal antibody 340:358 monoclonal antibody 340:358 The combination of production of monoclonal antibody and mass spectrometric analyses with reverse-phase (RP)-high performance liquid chromatography (HPLC) fractionation indicated that the O-GlcNAcylation is specific to the Ser(40) isoforms. 27615797 5 34 theme H2AS40Gc 657:664 arg1 Targets 646:652 Targets 646:652 Targets of H2AS40Gc 646:664 Targets of H2AS40Gc are distributed genome-wide and are dramatically changed during the process of differentiation in mouse trophoblast stem cells. 27615797 3 35 theme antibody 351:358 arg1 production 326:335 production 326:335 production of monoclonal antibody 326:358 The combination of production of monoclonal antibody and mass spectrometric analyses with reverse-phase (RP)-high performance liquid chromatography (HPLC) fractionation indicated that the O-GlcNAcylation is specific to the Ser(40) isoforms. 27615797 5 36 theme trophoblast 770:780 arg1 cells 787:791 mouse trophoblast stem cells 764:791 mouse trophoblast stem cells 764:791 Targets of H2AS40Gc are distributed genome-wide and are dramatically changed during the process of differentiation in mouse trophoblast stem cells. 27615797 3 37 with combination 311:321 arg1 chromatography 440:453 reverse-phase (RP)-high performance liquid chromatography 397:453 reverse-phase (RP)-high performance liquid chromatography (HPLC) 397:460 The combination of production of monoclonal antibody and mass spectrometric analyses with reverse-phase (RP)-high performance liquid chromatography (HPLC) fractionation indicated that the O-GlcNAcylation is specific to the Ser(40) isoforms. 27615797 3 37 with combination 311:321 arg1 HPLC 456:459 HPLC 456:459 HPLC 456:459 The combination of production of monoclonal antibody and mass spectrometric analyses with reverse-phase (RP)-high performance liquid chromatography (HPLC) fractionation indicated that the O-GlcNAcylation is specific to the Ser(40) isoforms. 27615797 7 38 theme H2A 1062:1064 arg1 isoforms 1050:1057 Ser(40) isoforms 1042:1057 Ser(40) isoforms of H2A 1042:1064 Genome database surveys revealed that Ser(40) isoforms of H2A emerged in Marsupialia and persisted thereafter in mammals. 27615797 5 39 from process 734:740 arg1 cells 787:791 mouse trophoblast stem cells 764:791 mouse trophoblast stem cells 764:791 Targets of H2AS40Gc are distributed genome-wide and are dramatically changed during the process of differentiation in mouse trophoblast stem cells. 27615797 8 40 theme placental 1288:1296 arg1 animals 1298:1304 placental animals 1288:1304 placental animals 1288:1304 We propose that the emergence of H2A Ser(40) and its O-GlcNAcylation linked a genetic event to genome-wide epigenetic events that correlate with the evolution of placental animals. 27615797 3 41 theme reverse-phase 397:409 arg1 chromatography 440:453 reverse-phase (RP)-high performance liquid chromatography 397:453 reverse-phase (RP)-high performance liquid chromatography (HPLC) 397:460 The combination of production of monoclonal antibody and mass spectrometric analyses with reverse-phase (RP)-high performance liquid chromatography (HPLC) fractionation indicated that the O-GlcNAcylation is specific to the Ser(40) isoforms. 27615797 3 41 theme reverse-phase 397:409 arg1 HPLC 456:459 HPLC 456:459 HPLC 456:459 The combination of production of monoclonal antibody and mass spectrometric analyses with reverse-phase (RP)-high performance liquid chromatography (HPLC) fractionation indicated that the O-GlcNAcylation is specific to the Ser(40) isoforms. 27615797 8 42 theme epigenetic 1233:1242 arg1 events 1244:1249 genome-wide epigenetic events 1221:1249 genome-wide epigenetic events that correlate with the evolution of placental animals 1221:1304 We propose that the emergence of H2A Ser(40) and its O-GlcNAcylation linked a genetic event to genome-wide epigenetic events that correlate with the evolution of placental animals. 27615797 1 43 from Ser 186:188 arg1 modification 155:166 newly discovered O-linked-N-acetylglucosamine (O-GlcNAc) modification 98:166 newly discovered O-linked-N-acetylglucosamine (O-GlcNAc) modification of histone H2A at Ser(40) (H2AS40Gc) 98:203 We report here newly discovered O-linked-N-acetylglucosamine (O-GlcNAc) modification of histone H2A at Ser(40) (H2AS40Gc). 27615797 3 44 theme spectrometric 369:381 arg1 analyses 383:390 mass spectrometric analyses 364:390 mass spectrometric analyses with reverse-phase (RP)-high performance liquid chromatography (HPLC) 364:460 The combination of production of monoclonal antibody and mass spectrometric analyses with reverse-phase (RP)-high performance liquid chromatography (HPLC) fractionation indicated that the O-GlcNAcylation is specific to the Ser(40) isoforms. 27615797 5 45 theme mouse 764:768 arg1 cells 787:791 mouse trophoblast stem cells 764:791 mouse trophoblast stem cells 764:791 Targets of H2AS40Gc are distributed genome-wide and are dramatically changed during the process of differentiation in mouse trophoblast stem cells. 27615797 3 46 theme Ser 530:532 arg1 isoforms 538:545 the Ser(40) isoforms 526:545 the Ser(40) isoforms 526:545 The combination of production of monoclonal antibody and mass spectrometric analyses with reverse-phase (RP)-high performance liquid chromatography (HPLC) fractionation indicated that the O-GlcNAcylation is specific to the Ser(40) isoforms. 27615797 1 47 mod modification 155:166 arg1 H2A 179:181 histone H2A 171:181 histone H2A 171:181 We report here newly discovered O-linked-N-acetylglucosamine (O-GlcNAc) modification of histone H2A at Ser(40) (H2AS40Gc). 27615797 1 47 mod modification 155:166 arg3 O-linked-N-acetylglucosamine 115:142 newly discovered O-linked-N-acetylglucosamine (O-GlcNAc) modification 98:166 newly discovered O-linked-N-acetylglucosamine (O-GlcNAc) modification of histone H2A at Ser(40) (H2AS40Gc) 98:203 We report here newly discovered O-linked-N-acetylglucosamine (O-GlcNAc) modification of histone H2A at Ser(40) (H2AS40Gc). 27615797 1 47 mod modification 155:166 arg3 O-GlcNAc 145:152 newly discovered O-linked-N-acetylglucosamine (O-GlcNAc) modification 98:166 newly discovered O-linked-N-acetylglucosamine (O-GlcNAc) modification of histone H2A at Ser(40) (H2AS40Gc) 98:203 We report here newly discovered O-linked-N-acetylglucosamine (O-GlcNAc) modification of histone H2A at Ser(40) (H2AS40Gc). 27615797 8 48 theme H2A 1159:1161 arg1 40 1167:1168 40 1167:1168 40 1167:1168 We propose that the emergence of H2A Ser(40) and its O-GlcNAcylation linked a genetic event to genome-wide epigenetic events that correlate with the evolution of placental animals. 27615797 8 48 theme H2A 1159:1161 arg1 Ser 1163:1165 H2A Ser 1159:1165 H2A Ser(40) 1159:1169 We propose that the emergence of H2A Ser(40) and its O-GlcNAcylation linked a genetic event to genome-wide epigenetic events that correlate with the evolution of placental animals. 27615797 6 49 theme non-mammalian 885:897 arg1 silkworms 953:961 silkworms 953:961 silkworms 953:961 In addition to the mouse, H2AS40Gc was also detected in humans, macaques and cows, whereas non-mammalian species possessing only the Ala(40) isoforms, such as silkworms, zebrafish and Xenopus showed no signal. 27615797 6 49 theme non-mammalian 885:897 arg1 species 899:905 non-mammalian species 885:905 non-mammalian species 885:905 In addition to the mouse, H2AS40Gc was also detected in humans, macaques and cows, whereas non-mammalian species possessing only the Ala(40) isoforms, such as silkworms, zebrafish and Xenopus showed no signal. 27615797 0 50 theme H2A 46:48 arg1 O-GlcNAcylation 6:20 Novel O-GlcNAcylation 0:20 Novel O-GlcNAcylation on Ser(40) of canonical H2A 0:48 Novel O-GlcNAcylation on Ser(40) of canonical H2A isoforms specific to viviparity. 27615797 8 51 theme animals 1298:1304 arg1 evolution 1275:1283 the evolution 1271:1283 the evolution of placental animals 1271:1304 We propose that the emergence of H2A Ser(40) and its O-GlcNAcylation linked a genetic event to genome-wide epigenetic events that correlate with the evolution of placental animals. 27615797 8 52 attach linked 1195:1200 arg2 emergence 1146:1154 the emergence 1142:1154 the emergence of H2A Ser(40) and its O-GlcNAcylation 1142:1193 We propose that the emergence of H2A Ser(40) and its O-GlcNAcylation linked a genetic event to genome-wide epigenetic events that correlate with the evolution of placental animals. 27615797 8 52 attach linked 1195:1200 arg1 events 1244:1249 genome-wide epigenetic events 1221:1249 genome-wide epigenetic events that correlate with the evolution of placental animals 1221:1304 We propose that the emergence of H2A Ser(40) and its O-GlcNAcylation linked a genetic event to genome-wide epigenetic events that correlate with the evolution of placental animals. 27615797 1 53 theme O-linked-N-acetylglucosamine 115:142 arg1 modification 155:166 newly discovered O-linked-N-acetylglucosamine (O-GlcNAc) modification 98:166 newly discovered O-linked-N-acetylglucosamine (O-GlcNAc) modification of histone H2A at Ser(40) (H2AS40Gc) 98:203 We report here newly discovered O-linked-N-acetylglucosamine (O-GlcNAc) modification of histone H2A at Ser(40) (H2AS40Gc). 27615797 0 54 theme canonical 36:44 arg1 H2A 46:48 canonical H2A 36:48 canonical H2A 36:48 Novel O-GlcNAcylation on Ser(40) of canonical H2A isoforms specific to viviparity. 27615797 2 55 contain have 261:264 arg2 Ser 266:268 Ser(40) 266:272 Ser(40) 266:272 The mouse genome contains 18 H2A isoforms, of which 13 have Ser(40) and the other five have Ala(40). 27615797 2 55 contain have 261:264 arg1 13 258:259 13 258:259 13 258:259 The mouse genome contains 18 H2A isoforms, of which 13 have Ser(40) and the other five have Ala(40). 27615797 6 56 located detected 838:845 arg1 cows 871:874 cows 871:874 cows 871:874 In addition to the mouse, H2AS40Gc was also detected in humans, macaques and cows, whereas non-mammalian species possessing only the Ala(40) isoforms, such as silkworms, zebrafish and Xenopus showed no signal. 27615797 6 56 located detected 838:845 arg1 humans 850:855 humans 850:855 humans 850:855 In addition to the mouse, H2AS40Gc was also detected in humans, macaques and cows, whereas non-mammalian species possessing only the Ala(40) isoforms, such as silkworms, zebrafish and Xenopus showed no signal. 27615797 6 56 located detected 838:845 arg1 macaques 858:865 macaques 858:865 macaques 858:865 In addition to the mouse, H2AS40Gc was also detected in humans, macaques and cows, whereas non-mammalian species possessing only the Ala(40) isoforms, such as silkworms, zebrafish and Xenopus showed no signal. 27615797 6 56 located detected 838:845 arg2 H2AS40Gc 820:827 H2AS40Gc 820:827 H2AS40Gc 820:827 In addition to the mouse, H2AS40Gc was also detected in humans, macaques and cows, whereas non-mammalian species possessing only the Ala(40) isoforms, such as silkworms, zebrafish and Xenopus showed no signal. 27615797 3 57 theme -high 415:419 arg1 chromatography 440:453 reverse-phase (RP)-high performance liquid chromatography 397:453 reverse-phase (RP)-high performance liquid chromatography (HPLC) 397:460 The combination of production of monoclonal antibody and mass spectrometric analyses with reverse-phase (RP)-high performance liquid chromatography (HPLC) fractionation indicated that the O-GlcNAcylation is specific to the Ser(40) isoforms. 27615797 3 57 theme -high 415:419 arg1 HPLC 456:459 HPLC 456:459 HPLC 456:459 The combination of production of monoclonal antibody and mass spectrometric analyses with reverse-phase (RP)-high performance liquid chromatography (HPLC) fractionation indicated that the O-GlcNAcylation is specific to the Ser(40) isoforms. 26431879 0 0 theme transcriptional 86:100 arg1 activities 102:111 their transcriptional activities 80:111 their transcriptional activities 80:111 O-GlcNAc modification of Sp3 and Sp4 transcription factors negatively regulates their transcriptional activities. 26431879 4 1 theme O-GlcNAc 782:789 arg1 residues 791:798 O-GlcNAc residues 782:798 O-GlcNAc residues 782:798 We highlight the presence of O-GlcNAc residues in Sp3 and Sp4, but not Sp2, as demonstrated by their enrichment in GlcNAc positive protein fractions and by detection of O-GlcNAc residues on Sp3 and Sp4 co-expressed in Escherichia coli together with O-GlcNAc transferase (OGT) using an O-GlcNAc-specific antibody. 26431879 3 2 theme transcription 528:540 arg1 factors 542:548 transcription factors 528:548 transcription factors 528:548 In this study, we demonstrate the O-GlcNAc status of the Sp family members of transcription factors and the functional impact on their transcriptional activities. 26431879 3 3 from impact 569:574 arg1 activities 601:610 their transcriptional activities 579:610 their transcriptional activities 579:610 In this study, we demonstrate the O-GlcNAc status of the Sp family members of transcription factors and the functional impact on their transcriptional activities. 26431879 5 4 theme O-GlcNAc 988:995 arg1 sites 997:1001 O-GlcNAc sites 988:1001 O-GlcNAc sites 988:1001 Deletion mutants of Sp3 and Sp4 indicate that the majority of O-GlcNAc sites reside in their N-terminal transactivation domain. 26431879 4 5 from presence 630:637 arg1 Sp4 671:673 Sp4 671:673 Sp4 671:673 We highlight the presence of O-GlcNAc residues in Sp3 and Sp4, but not Sp2, as demonstrated by their enrichment in GlcNAc positive protein fractions and by detection of O-GlcNAc residues on Sp3 and Sp4 co-expressed in Escherichia coli together with O-GlcNAc transferase (OGT) using an O-GlcNAc-specific antibody. 26431879 4 5 from presence 630:637 arg1 Sp3 663:665 Sp3 663:665 Sp3 663:665 We highlight the presence of O-GlcNAc residues in Sp3 and Sp4, but not Sp2, as demonstrated by their enrichment in GlcNAc positive protein fractions and by detection of O-GlcNAc residues on Sp3 and Sp4 co-expressed in Escherichia coli together with O-GlcNAc transferase (OGT) using an O-GlcNAc-specific antibody. 26431879 3 6 theme transcriptional 585:599 arg1 activities 601:610 their transcriptional activities 579:610 their transcriptional activities 579:610 In this study, we demonstrate the O-GlcNAc status of the Sp family members of transcription factors and the functional impact on their transcriptional activities. 26431879 6 7 theme transcription 1204:1216 arg1 factors 1218:1224 transcription factors 1204:1224 transcription factors 1204:1224 Overall, using reporter gene assays and co-immunoprecipitations, we demonstrate a functional inhibitory role of O-GlcNAc modifications in Sp3 and Sp4 transcription factors. 26431879 5 8 theme Sp3 946:948 arg1 mutants 935:941 Deletion mutants 926:941 Deletion mutants of Sp3 and Sp4 926:956 Deletion mutants of Sp3 and Sp4 indicate that the majority of O-GlcNAc sites reside in their N-terminal transactivation domain. 26431879 5 9 theme Deletion 926:933 arg1 mutants 935:941 Deletion mutants 926:941 Deletion mutants of Sp3 and Sp4 926:956 Deletion mutants of Sp3 and Sp4 indicate that the majority of O-GlcNAc sites reside in their N-terminal transactivation domain. 26431879 4 10 theme residues 791:798 arg1 detection 769:777 detection 769:777 detection of O-GlcNAc residues on Sp3 and Sp4 co-expressed in Escherichia coli together with O-GlcNAc transferase (OGT) using an O-GlcNAc-specific antibody 769:923 We highlight the presence of O-GlcNAc residues in Sp3 and Sp4, but not Sp2, as demonstrated by their enrichment in GlcNAc positive protein fractions and by detection of O-GlcNAc residues on Sp3 and Sp4 co-expressed in Escherichia coli together with O-GlcNAc transferase (OGT) using an O-GlcNAc-specific antibody. 26431879 2 11 theme expression 427:436 arg1 regulation 438:447 gene expression regulation 422:447 gene expression regulation 422:447 O-GlcNAc modification is common among chromosome-associated proteins, such as transcription factors, suggesting its extensive involvement in gene expression regulation. 26431879 6 12 theme inhibitory 1147:1156 arg1 role 1158:1161 a functional inhibitory role 1134:1161 a functional inhibitory role of O-GlcNAc modifications in Sp3 and Sp4 transcription factors 1134:1224 Overall, using reporter gene assays and co-immunoprecipitations, we demonstrate a functional inhibitory role of O-GlcNAc modifications in Sp3 and Sp4 transcription factors. 26431879 2 13 theme O-GlcNAc 281:288 arg1 modification 290:301 O-GlcNAc modification 281:301 O-GlcNAc modification 281:301 O-GlcNAc modification is common among chromosome-associated proteins, such as transcription factors, suggesting its extensive involvement in gene expression regulation. 26431879 2 14 theme gene 422:425 arg1 regulation 438:447 gene expression regulation 422:447 gene expression regulation 422:447 O-GlcNAc modification is common among chromosome-associated proteins, such as transcription factors, suggesting its extensive involvement in gene expression regulation. 26431879 7 15 dep notion 1270:1275 arg1 modification 1291:1302 O-GlcNAc modification 1282:1302 O-GlcNAc modification 1282:1302 Thereby, our study strengthens the current notion that O-GlcNAc modification is an important regulator of protein interactome. 26431879 7 15 dep notion 1270:1275 arg1 regulator 1320:1328 an important regulator 1307:1328 an important regulator of protein interactome 1307:1351 Thereby, our study strengthens the current notion that O-GlcNAc modification is an important regulator of protein interactome. 26431879 6 16 dep Sp3 1192:1194 arg1 factors 1218:1224 transcription factors 1204:1224 transcription factors 1204:1224 Overall, using reporter gene assays and co-immunoprecipitations, we demonstrate a functional inhibitory role of O-GlcNAc modifications in Sp3 and Sp4 transcription factors. 26431879 0 17 theme O-GlcNAc 0:7 arg1 modification 9:20 O-GlcNAc modification 0:20 O-GlcNAc modification of Sp3 and Sp4 transcription factors 0:57 O-GlcNAc modification of Sp3 and Sp4 transcription factors negatively regulates their transcriptional activities. 26431879 4 18 theme O-GlcNAc 862:869 arg1 OGT 884:886 OGT 884:886 OGT 884:886 We highlight the presence of O-GlcNAc residues in Sp3 and Sp4, but not Sp2, as demonstrated by their enrichment in GlcNAc positive protein fractions and by detection of O-GlcNAc residues on Sp3 and Sp4 co-expressed in Escherichia coli together with O-GlcNAc transferase (OGT) using an O-GlcNAc-specific antibody. 26431879 4 18 theme O-GlcNAc 862:869 arg1 transferase 871:881 O-GlcNAc transferase 862:881 O-GlcNAc transferase (OGT) using an O-GlcNAc-specific antibody 862:923 We highlight the presence of O-GlcNAc residues in Sp3 and Sp4, but not Sp2, as demonstrated by their enrichment in GlcNAc positive protein fractions and by detection of O-GlcNAc residues on Sp3 and Sp4 co-expressed in Escherichia coli together with O-GlcNAc transferase (OGT) using an O-GlcNAc-specific antibody. 26431879 4 19 theme protein 744:750 arg1 fractions 752:760 GlcNAc positive protein fractions 728:760 GlcNAc positive protein fractions 728:760 We highlight the presence of O-GlcNAc residues in Sp3 and Sp4, but not Sp2, as demonstrated by their enrichment in GlcNAc positive protein fractions and by detection of O-GlcNAc residues on Sp3 and Sp4 co-expressed in Escherichia coli together with O-GlcNAc transferase (OGT) using an O-GlcNAc-specific antibody. 26431879 6 20 theme gene 1078:1081 arg1 assays 1083:1088 reporter gene assays 1069:1088 reporter gene assays 1069:1088 Overall, using reporter gene assays and co-immunoprecipitations, we demonstrate a functional inhibitory role of O-GlcNAc modifications in Sp3 and Sp4 transcription factors. 26431879 0 21 theme Sp3 25:27 arg1 modification 9:20 O-GlcNAc modification 0:20 O-GlcNAc modification of Sp3 and Sp4 transcription factors 0:57 O-GlcNAc modification of Sp3 and Sp4 transcription factors negatively regulates their transcriptional activities. 26431879 7 22 theme O-GlcNAc 1282:1289 arg1 modification 1291:1302 O-GlcNAc modification 1282:1302 O-GlcNAc modification 1282:1302 Thereby, our study strengthens the current notion that O-GlcNAc modification is an important regulator of protein interactome. 26431879 7 22 theme O-GlcNAc 1282:1289 arg1 regulator 1320:1328 an important regulator 1307:1328 an important regulator of protein interactome 1307:1351 Thereby, our study strengthens the current notion that O-GlcNAc modification is an important regulator of protein interactome. 26431879 2 23 theme chromosome-associated 319:339 arg1 factors 373:379 transcription factors 359:379 transcription factors 359:379 O-GlcNAc modification is common among chromosome-associated proteins, such as transcription factors, suggesting its extensive involvement in gene expression regulation. 26431879 2 23 theme chromosome-associated 319:339 arg1 proteins 341:348 chromosome-associated proteins 319:348 chromosome-associated proteins 319:348 O-GlcNAc modification is common among chromosome-associated proteins, such as transcription factors, suggesting its extensive involvement in gene expression regulation. 26431879 6 24 theme reporter 1069:1076 arg1 assays 1083:1088 reporter gene assays 1069:1088 reporter gene assays 1069:1088 Overall, using reporter gene assays and co-immunoprecipitations, we demonstrate a functional inhibitory role of O-GlcNAc modifications in Sp3 and Sp4 transcription factors. 26431879 5 25 theme Sp4 954:956 arg1 mutants 935:941 Deletion mutants 926:941 Deletion mutants of Sp3 and Sp4 926:956 Deletion mutants of Sp3 and Sp4 indicate that the majority of O-GlcNAc sites reside in their N-terminal transactivation domain. 26431879 3 26 theme members 517:523 arg1 impact 569:574 the functional impact 554:574 the functional impact on their transcriptional activities 554:610 In this study, we demonstrate the O-GlcNAc status of the Sp family members of transcription factors and the functional impact on their transcriptional activities. 26431879 3 26 theme members 517:523 arg1 status 493:498 the O-GlcNAc status 480:498 the O-GlcNAc status of the Sp family members of transcription factors 480:548 In this study, we demonstrate the O-GlcNAc status of the Sp family members of transcription factors and the functional impact on their transcriptional activities. 26431879 3 27 theme factors 542:548 arg1 members 517:523 the Sp family members 503:523 the Sp family members of transcription factors 503:548 In this study, we demonstrate the O-GlcNAc status of the Sp family members of transcription factors and the functional impact on their transcriptional activities. 26431879 0 28 theme Sp4 33:35 arg1 modification 9:20 O-GlcNAc modification 0:20 O-GlcNAc modification of Sp3 and Sp4 transcription factors 0:57 O-GlcNAc modification of Sp3 and Sp4 transcription factors negatively regulates their transcriptional activities. 26431879 2 29 theme transcription 359:371 arg1 factors 373:379 transcription factors 359:379 transcription factors 359:379 O-GlcNAc modification is common among chromosome-associated proteins, such as transcription factors, suggesting its extensive involvement in gene expression regulation. 26431879 3 30 theme functional 558:567 arg1 impact 569:574 the functional impact 554:574 the functional impact on their transcriptional activities 554:610 In this study, we demonstrate the O-GlcNAc status of the Sp family members of transcription factors and the functional impact on their transcriptional activities. 26431879 5 31 theme N-terminal 1019:1028 arg1 domain 1046:1051 their N-terminal transactivation domain 1013:1051 their N-terminal transactivation domain 1013:1051 Deletion mutants of Sp3 and Sp4 indicate that the majority of O-GlcNAc sites reside in their N-terminal transactivation domain. 26431879 1 32 theme proteins 214:221 arg1 myriad 204:209 a myriad 202:209 a myriad of proteins 202:221 The addition of O-linked N-acetylglucosamine (O-GlcNAc) on serine or threonine modifies a myriad of proteins and regulates their function, stability and localization. 26431879 5 33 theme transactivation 1030:1044 arg1 domain 1046:1051 their N-terminal transactivation domain 1013:1051 their N-terminal transactivation domain 1013:1051 Deletion mutants of Sp3 and Sp4 indicate that the majority of O-GlcNAc sites reside in their N-terminal transactivation domain. 26431879 3 34 theme O-GlcNAc 484:491 arg1 status 493:498 the O-GlcNAc status 480:498 the O-GlcNAc status of the Sp family members of transcription factors 480:548 In this study, we demonstrate the O-GlcNAc status of the Sp family members of transcription factors and the functional impact on their transcriptional activities. 26431879 4 35 theme O-GlcNAc-specific 898:914 arg1 antibody 916:923 an O-GlcNAc-specific antibody 895:923 an O-GlcNAc-specific antibody 895:923 We highlight the presence of O-GlcNAc residues in Sp3 and Sp4, but not Sp2, as demonstrated by their enrichment in GlcNAc positive protein fractions and by detection of O-GlcNAc residues on Sp3 and Sp4 co-expressed in Escherichia coli together with O-GlcNAc transferase (OGT) using an O-GlcNAc-specific antibody. 26431879 7 36 theme important 1310:1318 arg1 modification 1291:1302 O-GlcNAc modification 1282:1302 O-GlcNAc modification 1282:1302 Thereby, our study strengthens the current notion that O-GlcNAc modification is an important regulator of protein interactome. 26431879 7 36 theme important 1310:1318 arg1 regulator 1320:1328 an important regulator 1307:1328 an important regulator of protein interactome 1307:1351 Thereby, our study strengthens the current notion that O-GlcNAc modification is an important regulator of protein interactome. 26431879 2 37 from involvement 407:417 arg1 regulation 438:447 gene expression regulation 422:447 gene expression regulation 422:447 O-GlcNAc modification is common among chromosome-associated proteins, such as transcription factors, suggesting its extensive involvement in gene expression regulation. 26431879 3 38 theme family 510:515 arg1 members 517:523 the Sp family members 503:523 the Sp family members of transcription factors 503:548 In this study, we demonstrate the O-GlcNAc status of the Sp family members of transcription factors and the functional impact on their transcriptional activities. 26431879 0 39 theme transcription 37:49 arg1 factors 51:57 transcription factors 37:57 transcription factors 37:57 O-GlcNAc modification of Sp3 and Sp4 transcription factors negatively regulates their transcriptional activities. 26431879 6 40 theme functional 1136:1145 arg1 role 1158:1161 a functional inhibitory role 1134:1161 a functional inhibitory role of O-GlcNAc modifications in Sp3 and Sp4 transcription factors 1134:1224 Overall, using reporter gene assays and co-immunoprecipitations, we demonstrate a functional inhibitory role of O-GlcNAc modifications in Sp3 and Sp4 transcription factors. 26431879 6 41 theme modifications 1175:1187 arg1 role 1158:1161 a functional inhibitory role 1134:1161 a functional inhibitory role of O-GlcNAc modifications in Sp3 and Sp4 transcription factors 1134:1224 Overall, using reporter gene assays and co-immunoprecipitations, we demonstrate a functional inhibitory role of O-GlcNAc modifications in Sp3 and Sp4 transcription factors. 26431879 3 42 from status 493:498 arg1 activities 601:610 their transcriptional activities 579:610 their transcriptional activities 579:610 In this study, we demonstrate the O-GlcNAc status of the Sp family members of transcription factors and the functional impact on their transcriptional activities. 26431879 1 43 theme O-linked 130:137 arg1 N-acetylglucosamine 139:157 O-linked N-acetylglucosamine 130:157 O-linked N-acetylglucosamine (O-GlcNAc) 130:168 The addition of O-linked N-acetylglucosamine (O-GlcNAc) on serine or threonine modifies a myriad of proteins and regulates their function, stability and localization. 26431879 1 43 theme O-linked 130:137 arg1 O-GlcNAc 160:167 O-GlcNAc 160:167 O-GlcNAc 160:167 The addition of O-linked N-acetylglucosamine (O-GlcNAc) on serine or threonine modifies a myriad of proteins and regulates their function, stability and localization. 26431879 5 44 theme sites 997:1001 arg1 majority 976:983 the majority 972:983 the majority of O-GlcNAc sites 972:1001 Deletion mutants of Sp3 and Sp4 indicate that the majority of O-GlcNAc sites reside in their N-terminal transactivation domain. 26431879 0 45 dep Sp3 25:27 arg1 factors 51:57 transcription factors 37:57 transcription factors 37:57 O-GlcNAc modification of Sp3 and Sp4 transcription factors negatively regulates their transcriptional activities. 26431879 6 46 from role 1158:1161 arg1 Sp4 1200:1202 Sp4 1200:1202 Sp4 1200:1202 Overall, using reporter gene assays and co-immunoprecipitations, we demonstrate a functional inhibitory role of O-GlcNAc modifications in Sp3 and Sp4 transcription factors. 26431879 6 46 from role 1158:1161 arg1 Sp3 1192:1194 Sp3 1192:1194 Sp3 1192:1194 Overall, using reporter gene assays and co-immunoprecipitations, we demonstrate a functional inhibitory role of O-GlcNAc modifications in Sp3 and Sp4 transcription factors. 26431879 1 47 theme N-acetylglucosamine 139:157 arg1 addition 118:125 The addition 114:125 The addition of O-linked N-acetylglucosamine (O-GlcNAc) on serine or threonine 114:191 The addition of O-linked N-acetylglucosamine (O-GlcNAc) on serine or threonine modifies a myriad of proteins and regulates their function, stability and localization. 26431879 1 48 from addition 118:125 arg1 threonine 183:191 threonine 183:191 threonine 183:191 The addition of O-linked N-acetylglucosamine (O-GlcNAc) on serine or threonine modifies a myriad of proteins and regulates their function, stability and localization. 26431879 1 48 from addition 118:125 arg1 serine 173:178 serine 173:178 serine 173:178 The addition of O-linked N-acetylglucosamine (O-GlcNAc) on serine or threonine modifies a myriad of proteins and regulates their function, stability and localization. 26431879 4 49 theme O-GlcNAc 642:649 arg1 residues 651:658 O-GlcNAc residues 642:658 O-GlcNAc residues 642:658 We highlight the presence of O-GlcNAc residues in Sp3 and Sp4, but not Sp2, as demonstrated by their enrichment in GlcNAc positive protein fractions and by detection of O-GlcNAc residues on Sp3 and Sp4 co-expressed in Escherichia coli together with O-GlcNAc transferase (OGT) using an O-GlcNAc-specific antibody. 26431879 1 50 link O-linked 130:137 arg1 N-acetylglucosamine 139:157 O-linked N-acetylglucosamine 130:157 O-linked N-acetylglucosamine (O-GlcNAc) 130:168 The addition of O-linked N-acetylglucosamine (O-GlcNAc) on serine or threonine modifies a myriad of proteins and regulates their function, stability and localization. 26431879 1 50 link O-linked 130:137 arg1 O-GlcNAc 160:167 O-GlcNAc 160:167 O-GlcNAc 160:167 The addition of O-linked N-acetylglucosamine (O-GlcNAc) on serine or threonine modifies a myriad of proteins and regulates their function, stability and localization. 26431879 3 51 theme Sp 507:508 arg1 members 517:523 the Sp family members 503:523 the Sp family members of transcription factors 503:548 In this study, we demonstrate the O-GlcNAc status of the Sp family members of transcription factors and the functional impact on their transcriptional activities. 26431879 4 52 theme positive 735:742 arg1 fractions 752:760 GlcNAc positive protein fractions 728:760 GlcNAc positive protein fractions 728:760 We highlight the presence of O-GlcNAc residues in Sp3 and Sp4, but not Sp2, as demonstrated by their enrichment in GlcNAc positive protein fractions and by detection of O-GlcNAc residues on Sp3 and Sp4 co-expressed in Escherichia coli together with O-GlcNAc transferase (OGT) using an O-GlcNAc-specific antibody. 26431879 7 53 theme protein 1333:1339 arg1 interactome 1341:1351 protein interactome 1333:1351 protein interactome 1333:1351 Thereby, our study strengthens the current notion that O-GlcNAc modification is an important regulator of protein interactome. 26431879 7 54 theme interactome 1341:1351 arg1 modification 1291:1302 O-GlcNAc modification 1282:1302 O-GlcNAc modification 1282:1302 Thereby, our study strengthens the current notion that O-GlcNAc modification is an important regulator of protein interactome. 26431879 7 54 theme interactome 1341:1351 arg1 regulator 1320:1328 an important regulator 1307:1328 an important regulator of protein interactome 1307:1351 Thereby, our study strengthens the current notion that O-GlcNAc modification is an important regulator of protein interactome. 26431879 2 55 theme extensive 397:405 arg1 involvement 407:417 its extensive involvement 393:417 its extensive involvement in gene expression regulation 393:447 O-GlcNAc modification is common among chromosome-associated proteins, such as transcription factors, suggesting its extensive involvement in gene expression regulation. 26431879 4 56 from enrichment 714:723 arg1 fractions 752:760 GlcNAc positive protein fractions 728:760 GlcNAc positive protein fractions 728:760 We highlight the presence of O-GlcNAc residues in Sp3 and Sp4, but not Sp2, as demonstrated by their enrichment in GlcNAc positive protein fractions and by detection of O-GlcNAc residues on Sp3 and Sp4 co-expressed in Escherichia coli together with O-GlcNAc transferase (OGT) using an O-GlcNAc-specific antibody. 26431879 7 57 theme current 1262:1268 arg1 notion 1270:1275 the current notion 1258:1275 the current notion that O-GlcNAc modification is an important regulator of protein interactome 1258:1351 Thereby, our study strengthens the current notion that O-GlcNAc modification is an important regulator of protein interactome. 26431879 6 58 theme O-GlcNAc 1166:1173 arg1 modifications 1175:1187 O-GlcNAc modifications 1166:1187 O-GlcNAc modifications 1166:1187 Overall, using reporter gene assays and co-immunoprecipitations, we demonstrate a functional inhibitory role of O-GlcNAc modifications in Sp3 and Sp4 transcription factors. 26431879 4 59 attach presence 630:637 arg1 Sp4 671:673 Sp4 671:673 Sp4 671:673 We highlight the presence of O-GlcNAc residues in Sp3 and Sp4, but not Sp2, as demonstrated by their enrichment in GlcNAc positive protein fractions and by detection of O-GlcNAc residues on Sp3 and Sp4 co-expressed in Escherichia coli together with O-GlcNAc transferase (OGT) using an O-GlcNAc-specific antibody. 26431879 4 59 attach presence 630:637 arg1 Sp3 663:665 Sp3 663:665 Sp3 663:665 We highlight the presence of O-GlcNAc residues in Sp3 and Sp4, but not Sp2, as demonstrated by their enrichment in GlcNAc positive protein fractions and by detection of O-GlcNAc residues on Sp3 and Sp4 co-expressed in Escherichia coli together with O-GlcNAc transferase (OGT) using an O-GlcNAc-specific antibody. 26431879 4 59 attach presence 630:637 arg2 residues 651:658 O-GlcNAc residues 642:658 O-GlcNAc residues 642:658 We highlight the presence of O-GlcNAc residues in Sp3 and Sp4, but not Sp2, as demonstrated by their enrichment in GlcNAc positive protein fractions and by detection of O-GlcNAc residues on Sp3 and Sp4 co-expressed in Escherichia coli together with O-GlcNAc transferase (OGT) using an O-GlcNAc-specific antibody. 26431879 4 60 theme residues 651:658 arg1 presence 630:637 the presence 626:637 the presence of O-GlcNAc residues in Sp3 and Sp4 626:673 We highlight the presence of O-GlcNAc residues in Sp3 and Sp4, but not Sp2, as demonstrated by their enrichment in GlcNAc positive protein fractions and by detection of O-GlcNAc residues on Sp3 and Sp4 co-expressed in Escherichia coli together with O-GlcNAc transferase (OGT) using an O-GlcNAc-specific antibody. 25416863 0 0 theme skeletal 87:94 arg1 muscle 96:101 rat skeletal muscle 83:101 rat skeletal muscle 83:101 Glutathione depletion and acute exercise increase O-GlcNAc protein modification in rat skeletal muscle. 25416863 5 1 theme O-GlcNAcase 847:857 arg1 O-GlcNAc 763:770 O-GlcNAc 763:770 O-GlcNAc 763:770 White gastrocnemius and soleus muscles were analyzed for glutathione status, O-GlcNAc and O-GlcNAc transferase (OGT) protein levels, and mRNA expression of OGT, O-GlcNAcase and glutamine:fructose-6-phosphate amidotransferase. 25416863 5 1 theme O-GlcNAcase 847:857 arg1 status 755:760 glutathione status 743:760 glutathione status 743:760 White gastrocnemius and soleus muscles were analyzed for glutathione status, O-GlcNAc and O-GlcNAc transferase (OGT) protein levels, and mRNA expression of OGT, O-GlcNAcase and glutamine:fructose-6-phosphate amidotransferase. 25416863 5 1 theme O-GlcNAcase 847:857 arg1 levels 811:816 O-GlcNAc transferase (OGT) protein levels 776:816 O-GlcNAc transferase (OGT) protein levels 776:816 White gastrocnemius and soleus muscles were analyzed for glutathione status, O-GlcNAc and O-GlcNAc transferase (OGT) protein levels, and mRNA expression of OGT, O-GlcNAcase and glutamine:fructose-6-phosphate amidotransferase. 25416863 5 1 theme O-GlcNAcase 847:857 arg1 expression 828:837 mRNA expression 823:837 mRNA expression of OGT, O-GlcNAcase and glutamine:fructose-6-phosphate amidotransferase 823:909 White gastrocnemius and soleus muscles were analyzed for glutathione status, O-GlcNAc and O-GlcNAc transferase (OGT) protein levels, and mRNA expression of OGT, O-GlcNAcase and glutamine:fructose-6-phosphate amidotransferase. 25416863 5 2 theme soleus 710:715 arg1 muscles 717:723 White gastrocnemius and soleus muscles 686:723 White gastrocnemius and soleus muscles 686:723 White gastrocnemius and soleus muscles were analyzed for glutathione status, O-GlcNAc and O-GlcNAc transferase (OGT) protein levels, and mRNA expression of OGT, O-GlcNAcase and glutamine:fructose-6-phosphate amidotransferase. 25416863 0 3 theme rat 83:85 arg1 muscle 96:101 rat skeletal muscle 83:101 rat skeletal muscle 83:101 Glutathione depletion and acute exercise increase O-GlcNAc protein modification in rat skeletal muscle. 25416863 4 4 used used 600:603 arg2 DEM 591:593 DEM 591:593 DEM 591:593 Diethyl maleate (DEM) was used to deplete intracellular glutathione and rats were subjected to a treadmill run. 25416863 4 4 used used 600:603 arg2 maleate 582:588 Diethyl maleate 574:588 Diethyl maleate (DEM) 574:594 Diethyl maleate (DEM) was used to deplete intracellular glutathione and rats were subjected to a treadmill run. 25416863 3 5 theme rat 553:555 arg1 muscle 566:571 rat skeletal muscle 553:571 rat skeletal muscle 553:571 This study investigated the effects of glutathione depletion and acute exercise on O-GlcNAc protein modification in rat skeletal muscle. 25416863 11 6 theme cellular 1548:1555 arg1 adaptation 1557:1566 cellular adaptation 1548:1566 cellular adaptation to oxidative stress 1548:1586 This could represent one mechanism underlying cellular adaptation to oxidative stress and health benefits of exercise. 25416863 6 7 theme intracellular 942:954 arg1 glutathione 956:966 intracellular glutathione 942:966 intracellular glutathione 942:966 DEM and exercise both reduced intracellular glutathione and increased O-GlcNAc. 25416863 5 8 theme gastrocnemius 692:704 arg1 muscles 717:723 White gastrocnemius and soleus muscles 686:723 White gastrocnemius and soleus muscles 686:723 White gastrocnemius and soleus muscles were analyzed for glutathione status, O-GlcNAc and O-GlcNAc transferase (OGT) protein levels, and mRNA expression of OGT, O-GlcNAcase and glutamine:fructose-6-phosphate amidotransferase. 25416863 3 9 theme skeletal 557:564 arg1 muscle 566:571 rat skeletal muscle 553:571 rat skeletal muscle 553:571 This study investigated the effects of glutathione depletion and acute exercise on O-GlcNAc protein modification in rat skeletal muscle. 25416863 11 10 theme health 1592:1597 arg1 benefits 1599:1606 health benefits 1592:1606 health benefits of exercise 1592:1618 This could represent one mechanism underlying cellular adaptation to oxidative stress and health benefits of exercise. 25416863 9 11 from different 1169:1177 arg1 muscles 1190:1196 the two muscles 1182:1196 the two muscles 1182:1196 The changes in the mRNA levels of O-GlcNAc enzymes were different in the two muscles, potentially resulting from different rates of oxidative stress and metabolic demands between the muscle types. 25416863 10 12 theme skeletal 1389:1396 arg1 muscle 1398:1403 skeletal muscle 1389:1403 skeletal muscle 1389:1403 These findings indicate that oxidative environment promotes O-GlcNAcylation in skeletal muscle and suggest an interrelationship between cellular redox state and O-GlcNAc protein modification. 25416863 7 13 theme OGT 1008:1010 arg1 expression 1020:1029 OGT protein expression 1008:1029 OGT protein expression 1008:1029 DEM upregulated OGT protein expression. 25416863 10 14 theme oxidative 1339:1347 arg1 environment 1349:1359 oxidative environment 1339:1359 oxidative environment 1339:1359 These findings indicate that oxidative environment promotes O-GlcNAcylation in skeletal muscle and suggest an interrelationship between cellular redox state and O-GlcNAc protein modification. 25416863 4 15 theme intracellular 616:628 arg1 glutathione 630:640 intracellular glutathione 616:640 intracellular glutathione 616:640 Diethyl maleate (DEM) was used to deplete intracellular glutathione and rats were subjected to a treadmill run. 25416863 5 16 theme O-GlcNAc 776:783 arg1 OGT 798:800 OGT 798:800 OGT 798:800 White gastrocnemius and soleus muscles were analyzed for glutathione status, O-GlcNAc and O-GlcNAc transferase (OGT) protein levels, and mRNA expression of OGT, O-GlcNAcase and glutamine:fructose-6-phosphate amidotransferase. 25416863 5 16 theme O-GlcNAc 776:783 arg1 transferase 785:795 O-GlcNAc transferase 776:795 O-GlcNAc transferase (OGT) protein levels 776:816 White gastrocnemius and soleus muscles were analyzed for glutathione status, O-GlcNAc and O-GlcNAc transferase (OGT) protein levels, and mRNA expression of OGT, O-GlcNAcase and glutamine:fructose-6-phosphate amidotransferase. 25416863 10 17 theme protein 1480:1486 arg1 modification 1488:1499 O-GlcNAc protein modification 1471:1499 O-GlcNAc protein modification 1471:1499 These findings indicate that oxidative environment promotes O-GlcNAcylation in skeletal muscle and suggest an interrelationship between cellular redox state and O-GlcNAc protein modification. 25416863 7 18 theme protein 1012:1018 arg1 expression 1020:1029 OGT protein expression 1008:1029 OGT protein expression 1008:1029 DEM upregulated OGT protein expression. 25416863 8 19 dep significant 1070:1080 arg1 < 1104:1104 P < 0.05 1102:1109 P < 0.05 1102:1109 The effects of the interventions were significant 4 h after exercise (P < 0.05). 25416863 8 19 dep significant 1070:1080 arg1 significant 1070:1080 significant 1070:1080 significant 1070:1080 The effects of the interventions were significant 4 h after exercise (P < 0.05). 25416863 8 19 dep significant 1070:1080 arg1 effects 1036:1042 The effects 1032:1042 The effects of the interventions 1032:1063 The effects of the interventions were significant 4 h after exercise (P < 0.05). 25416863 2 20 theme exercise 427:434 arg1 context 416:422 the context 412:422 the context of exercise 412:434 Although many skeletal muscle proteins are O-GlcNAcylated, the modification has not been extensively studied in this tissue, especially in the context of exercise. 25416863 5 21 theme transferase 785:795 arg1 levels 811:816 O-GlcNAc transferase (OGT) protein levels 776:816 O-GlcNAc transferase (OGT) protein levels 776:816 White gastrocnemius and soleus muscles were analyzed for glutathione status, O-GlcNAc and O-GlcNAc transferase (OGT) protein levels, and mRNA expression of OGT, O-GlcNAcase and glutamine:fructose-6-phosphate amidotransferase. 25416863 8 22 theme P 1102:1102 arg1 < 1104:1104 P < 0.05 1102:1109 P < 0.05 1102:1109 The effects of the interventions were significant 4 h after exercise (P < 0.05). 25416863 8 22 theme P 1102:1102 arg1 significant 1070:1080 significant 1070:1080 significant 1070:1080 The effects of the interventions were significant 4 h after exercise (P < 0.05). 25416863 8 22 theme P 1102:1102 arg1 effects 1036:1042 The effects 1032:1042 The effects of the interventions 1032:1063 The effects of the interventions were significant 4 h after exercise (P < 0.05). 25416863 9 23 theme different 1226:1234 arg1 rates 1236:1240 different rates 1226:1240 different rates of oxidative stress and metabolic demands between the muscle types 1226:1307 The changes in the mRNA levels of O-GlcNAc enzymes were different in the two muscles, potentially resulting from different rates of oxidative stress and metabolic demands between the muscle types. 25416863 0 24 theme Glutathione 0:10 arg1 depletion 12:20 Glutathione depletion 0:20 Glutathione depletion 0:20 Glutathione depletion and acute exercise increase O-GlcNAc protein modification in rat skeletal muscle. 25416863 3 25 theme glutathione 476:486 arg1 depletion 488:496 glutathione depletion 476:496 glutathione depletion 476:496 This study investigated the effects of glutathione depletion and acute exercise on O-GlcNAc protein modification in rat skeletal muscle. 25416863 5 26 theme protein 803:809 arg1 levels 811:816 O-GlcNAc transferase (OGT) protein levels 776:816 O-GlcNAc transferase (OGT) protein levels 776:816 White gastrocnemius and soleus muscles were analyzed for glutathione status, O-GlcNAc and O-GlcNAc transferase (OGT) protein levels, and mRNA expression of OGT, O-GlcNAcase and glutamine:fructose-6-phosphate amidotransferase. 25416863 8 27 theme interventions 1051:1063 arg1 < 1104:1104 P < 0.05 1102:1109 P < 0.05 1102:1109 The effects of the interventions were significant 4 h after exercise (P < 0.05). 25416863 8 27 theme interventions 1051:1063 arg1 significant 1070:1080 significant 1070:1080 significant 1070:1080 The effects of the interventions were significant 4 h after exercise (P < 0.05). 25416863 8 27 theme interventions 1051:1063 arg1 effects 1036:1042 The effects 1032:1042 The effects of the interventions 1032:1063 The effects of the interventions were significant 4 h after exercise (P < 0.05). 25416863 1 28 with modification 123:134 arg1 β-N-acetylglucosamine 176:196 O-linked β-N-acetylglucosamine 167:196 O-linked β-N-acetylglucosamine (O-GlcNAc) 167:207 Post-translational modification of intracellular proteins with O-linked β-N-acetylglucosamine (O-GlcNAc) profoundly affects protein structure, function, and metabolism. 25416863 1 28 with modification 123:134 arg1 O-GlcNAc 199:206 O-GlcNAc 199:206 O-GlcNAc 199:206 Post-translational modification of intracellular proteins with O-linked β-N-acetylglucosamine (O-GlcNAc) profoundly affects protein structure, function, and metabolism. 25416863 10 29 theme O-GlcNAc 1471:1478 arg1 modification 1488:1499 O-GlcNAc protein modification 1471:1499 O-GlcNAc protein modification 1471:1499 These findings indicate that oxidative environment promotes O-GlcNAcylation in skeletal muscle and suggest an interrelationship between cellular redox state and O-GlcNAc protein modification. 25416863 10 30 theme cellular 1446:1453 arg1 state 1461:1465 cellular redox state 1446:1465 cellular redox state 1446:1465 These findings indicate that oxidative environment promotes O-GlcNAcylation in skeletal muscle and suggest an interrelationship between cellular redox state and O-GlcNAc protein modification. 25416863 1 31 theme protein 228:234 arg1 structure 236:244 protein structure 228:244 protein structure 228:244 Post-translational modification of intracellular proteins with O-linked β-N-acetylglucosamine (O-GlcNAc) profoundly affects protein structure, function, and metabolism. 25416863 0 32 theme acute 26:30 arg1 exercise 32:39 acute exercise 26:39 acute exercise 26:39 Glutathione depletion and acute exercise increase O-GlcNAc protein modification in rat skeletal muscle. 25416863 3 33 from modification 537:548 arg1 muscle 566:571 rat skeletal muscle 553:571 rat skeletal muscle 553:571 This study investigated the effects of glutathione depletion and acute exercise on O-GlcNAc protein modification in rat skeletal muscle. 25416863 1 34 theme Post-translational 104:121 arg1 modification 123:134 Post-translational modification 104:134 Post-translational modification of intracellular proteins with O-linked β-N-acetylglucosamine (O-GlcNAc) 104:207 Post-translational modification of intracellular proteins with O-linked β-N-acetylglucosamine (O-GlcNAc) profoundly affects protein structure, function, and metabolism. 25416863 9 35 theme mRNA 1132:1135 arg1 levels 1137:1142 the mRNA levels 1128:1142 the mRNA levels of O-GlcNAc enzymes 1128:1162 The changes in the mRNA levels of O-GlcNAc enzymes were different in the two muscles, potentially resulting from different rates of oxidative stress and metabolic demands between the muscle types. 25416863 3 36 theme acute 502:506 arg1 exercise 508:515 acute exercise 502:515 acute exercise 502:515 This study investigated the effects of glutathione depletion and acute exercise on O-GlcNAc protein modification in rat skeletal muscle. 25416863 5 37 theme glutathione 743:753 arg1 status 755:760 glutathione status 743:760 glutathione status 743:760 White gastrocnemius and soleus muscles were analyzed for glutathione status, O-GlcNAc and O-GlcNAc transferase (OGT) protein levels, and mRNA expression of OGT, O-GlcNAcase and glutamine:fructose-6-phosphate amidotransferase. 25416863 9 38 theme stress 1255:1260 arg1 rates 1236:1240 different rates 1226:1240 different rates of oxidative stress and metabolic demands between the muscle types 1226:1307 The changes in the mRNA levels of O-GlcNAc enzymes were different in the two muscles, potentially resulting from different rates of oxidative stress and metabolic demands between the muscle types. 25416863 5 39 theme White 686:690 arg1 muscles 717:723 White gastrocnemius and soleus muscles 686:723 White gastrocnemius and soleus muscles 686:723 White gastrocnemius and soleus muscles were analyzed for glutathione status, O-GlcNAc and O-GlcNAc transferase (OGT) protein levels, and mRNA expression of OGT, O-GlcNAcase and glutamine:fructose-6-phosphate amidotransferase. 25416863 3 40 theme exercise 508:515 arg1 effects 465:471 the effects 461:471 the effects of glutathione depletion and acute exercise on O-GlcNAc protein modification in rat skeletal muscle 461:571 This study investigated the effects of glutathione depletion and acute exercise on O-GlcNAc protein modification in rat skeletal muscle. 25416863 8 41 dep h 1084:1084 arg1 exercise 1092:1099 exercise 1092:1099 exercise 1092:1099 The effects of the interventions were significant 4 h after exercise (P < 0.05). 25416863 1 42 link O-linked 167:174 arg1 β-N-acetylglucosamine 176:196 O-linked β-N-acetylglucosamine 167:196 O-linked β-N-acetylglucosamine (O-GlcNAc) 167:207 Post-translational modification of intracellular proteins with O-linked β-N-acetylglucosamine (O-GlcNAc) profoundly affects protein structure, function, and metabolism. 25416863 1 42 link O-linked 167:174 arg1 O-GlcNAc 199:206 O-GlcNAc 199:206 O-GlcNAc 199:206 Post-translational modification of intracellular proteins with O-linked β-N-acetylglucosamine (O-GlcNAc) profoundly affects protein structure, function, and metabolism. 25416863 5 43 theme glutamine 863:871 arg1 O-GlcNAc 763:770 O-GlcNAc 763:770 O-GlcNAc 763:770 White gastrocnemius and soleus muscles were analyzed for glutathione status, O-GlcNAc and O-GlcNAc transferase (OGT) protein levels, and mRNA expression of OGT, O-GlcNAcase and glutamine:fructose-6-phosphate amidotransferase. 25416863 5 43 theme glutamine 863:871 arg1 status 755:760 glutathione status 743:760 glutathione status 743:760 White gastrocnemius and soleus muscles were analyzed for glutathione status, O-GlcNAc and O-GlcNAc transferase (OGT) protein levels, and mRNA expression of OGT, O-GlcNAcase and glutamine:fructose-6-phosphate amidotransferase. 25416863 5 43 theme glutamine 863:871 arg1 levels 811:816 O-GlcNAc transferase (OGT) protein levels 776:816 O-GlcNAc transferase (OGT) protein levels 776:816 White gastrocnemius and soleus muscles were analyzed for glutathione status, O-GlcNAc and O-GlcNAc transferase (OGT) protein levels, and mRNA expression of OGT, O-GlcNAcase and glutamine:fructose-6-phosphate amidotransferase. 25416863 5 43 theme glutamine 863:871 arg1 expression 828:837 mRNA expression 823:837 mRNA expression of OGT, O-GlcNAcase and glutamine:fructose-6-phosphate amidotransferase 823:909 White gastrocnemius and soleus muscles were analyzed for glutathione status, O-GlcNAc and O-GlcNAc transferase (OGT) protein levels, and mRNA expression of OGT, O-GlcNAcase and glutamine:fructose-6-phosphate amidotransferase. 25416863 3 44 theme depletion 488:496 arg1 effects 465:471 the effects 461:471 the effects of glutathione depletion and acute exercise on O-GlcNAc protein modification in rat skeletal muscle 461:571 This study investigated the effects of glutathione depletion and acute exercise on O-GlcNAc protein modification in rat skeletal muscle. 25416863 5 45 theme fructose-6-phosphate 873:892 arg1 amidotransferase 894:909 fructose-6-phosphate amidotransferase 873:909 glutamine:fructose-6-phosphate amidotransferase 863:909 White gastrocnemius and soleus muscles were analyzed for glutathione status, O-GlcNAc and O-GlcNAc transferase (OGT) protein levels, and mRNA expression of OGT, O-GlcNAcase and glutamine:fructose-6-phosphate amidotransferase. 25416863 4 46 theme Diethyl 574:580 arg1 maleate 582:588 Diethyl maleate 574:588 Diethyl maleate (DEM) 574:594 Diethyl maleate (DEM) was used to deplete intracellular glutathione and rats were subjected to a treadmill run. 25416863 4 46 theme Diethyl 574:580 arg1 DEM 591:593 DEM 591:593 DEM 591:593 Diethyl maleate (DEM) was used to deplete intracellular glutathione and rats were subjected to a treadmill run. 25416863 9 47 theme metabolic 1266:1274 arg1 demands 1276:1282 metabolic demands 1266:1282 metabolic demands 1266:1282 The changes in the mRNA levels of O-GlcNAc enzymes were different in the two muscles, potentially resulting from different rates of oxidative stress and metabolic demands between the muscle types. 25416863 5 48 theme OGT 842:844 arg1 O-GlcNAc 763:770 O-GlcNAc 763:770 O-GlcNAc 763:770 White gastrocnemius and soleus muscles were analyzed for glutathione status, O-GlcNAc and O-GlcNAc transferase (OGT) protein levels, and mRNA expression of OGT, O-GlcNAcase and glutamine:fructose-6-phosphate amidotransferase. 25416863 5 48 theme OGT 842:844 arg1 status 755:760 glutathione status 743:760 glutathione status 743:760 White gastrocnemius and soleus muscles were analyzed for glutathione status, O-GlcNAc and O-GlcNAc transferase (OGT) protein levels, and mRNA expression of OGT, O-GlcNAcase and glutamine:fructose-6-phosphate amidotransferase. 25416863 5 48 theme OGT 842:844 arg1 levels 811:816 O-GlcNAc transferase (OGT) protein levels 776:816 O-GlcNAc transferase (OGT) protein levels 776:816 White gastrocnemius and soleus muscles were analyzed for glutathione status, O-GlcNAc and O-GlcNAc transferase (OGT) protein levels, and mRNA expression of OGT, O-GlcNAcase and glutamine:fructose-6-phosphate amidotransferase. 25416863 5 48 theme OGT 842:844 arg1 expression 828:837 mRNA expression 823:837 mRNA expression of OGT, O-GlcNAcase and glutamine:fructose-6-phosphate amidotransferase 823:909 White gastrocnemius and soleus muscles were analyzed for glutathione status, O-GlcNAc and O-GlcNAc transferase (OGT) protein levels, and mRNA expression of OGT, O-GlcNAcase and glutamine:fructose-6-phosphate amidotransferase. 25416863 9 49 theme O-GlcNAc 1147:1154 arg1 enzymes 1156:1162 O-GlcNAc enzymes 1147:1162 O-GlcNAc enzymes 1147:1162 The changes in the mRNA levels of O-GlcNAc enzymes were different in the two muscles, potentially resulting from different rates of oxidative stress and metabolic demands between the muscle types. 25416863 4 50 theme treadmill 671:679 arg1 run 681:683 a treadmill run 669:683 a treadmill run 669:683 Diethyl maleate (DEM) was used to deplete intracellular glutathione and rats were subjected to a treadmill run. 25416863 0 51 theme protein 59:65 arg1 modification 67:78 O-GlcNAc protein modification 50:78 O-GlcNAc protein modification 50:78 Glutathione depletion and acute exercise increase O-GlcNAc protein modification in rat skeletal muscle. 25416863 5 52 theme mRNA 823:826 arg1 expression 828:837 mRNA expression 823:837 mRNA expression of OGT, O-GlcNAcase and glutamine:fructose-6-phosphate amidotransferase 823:909 White gastrocnemius and soleus muscles were analyzed for glutathione status, O-GlcNAc and O-GlcNAc transferase (OGT) protein levels, and mRNA expression of OGT, O-GlcNAcase and glutamine:fructose-6-phosphate amidotransferase. 25416863 9 53 theme demands 1276:1282 arg1 rates 1236:1240 different rates 1226:1240 different rates of oxidative stress and metabolic demands between the muscle types 1226:1307 The changes in the mRNA levels of O-GlcNAc enzymes were different in the two muscles, potentially resulting from different rates of oxidative stress and metabolic demands between the muscle types. 25416863 9 54 theme enzymes 1156:1162 arg1 levels 1137:1142 the mRNA levels 1128:1142 the mRNA levels of O-GlcNAc enzymes 1128:1162 The changes in the mRNA levels of O-GlcNAc enzymes were different in the two muscles, potentially resulting from different rates of oxidative stress and metabolic demands between the muscle types. 25416863 3 55 theme protein 529:535 arg1 modification 537:548 O-GlcNAc protein modification 520:548 O-GlcNAc protein modification in rat skeletal muscle 520:571 This study investigated the effects of glutathione depletion and acute exercise on O-GlcNAc protein modification in rat skeletal muscle. 25416863 0 56 theme O-GlcNAc 50:57 arg1 modification 67:78 O-GlcNAc protein modification 50:78 O-GlcNAc protein modification 50:78 Glutathione depletion and acute exercise increase O-GlcNAc protein modification in rat skeletal muscle. 25416863 1 57 theme intracellular 139:151 arg1 proteins 153:160 intracellular proteins 139:160 intracellular proteins 139:160 Post-translational modification of intracellular proteins with O-linked β-N-acetylglucosamine (O-GlcNAc) profoundly affects protein structure, function, and metabolism. 25416863 11 58 theme oxidative 1571:1579 arg1 stress 1581:1586 oxidative stress 1571:1586 oxidative stress 1571:1586 This could represent one mechanism underlying cellular adaptation to oxidative stress and health benefits of exercise. 25416863 9 59 theme oxidative 1245:1253 arg1 stress 1255:1260 oxidative stress 1245:1260 oxidative stress 1245:1260 The changes in the mRNA levels of O-GlcNAc enzymes were different in the two muscles, potentially resulting from different rates of oxidative stress and metabolic demands between the muscle types. 25416863 9 60 from changes 1117:1123 arg1 levels 1137:1142 the mRNA levels 1128:1142 the mRNA levels of O-GlcNAc enzymes 1128:1162 The changes in the mRNA levels of O-GlcNAc enzymes were different in the two muscles, potentially resulting from different rates of oxidative stress and metabolic demands between the muscle types. 25416863 5 61 dep glutamine 863:871 arg1 amidotransferase 894:909 fructose-6-phosphate amidotransferase 873:909 glutamine:fructose-6-phosphate amidotransferase 863:909 White gastrocnemius and soleus muscles were analyzed for glutathione status, O-GlcNAc and O-GlcNAc transferase (OGT) protein levels, and mRNA expression of OGT, O-GlcNAcase and glutamine:fructose-6-phosphate amidotransferase. 25416863 10 62 theme redox 1455:1459 arg1 state 1461:1465 cellular redox state 1446:1465 cellular redox state 1446:1465 These findings indicate that oxidative environment promotes O-GlcNAcylation in skeletal muscle and suggest an interrelationship between cellular redox state and O-GlcNAc protein modification. 25416863 1 63 theme proteins 153:160 arg1 modification 123:134 Post-translational modification 104:134 Post-translational modification of intracellular proteins with O-linked β-N-acetylglucosamine (O-GlcNAc) 104:207 Post-translational modification of intracellular proteins with O-linked β-N-acetylglucosamine (O-GlcNAc) profoundly affects protein structure, function, and metabolism. 25416863 9 64 theme muscle 1296:1301 arg1 types 1303:1307 the muscle types 1292:1307 the muscle types 1292:1307 The changes in the mRNA levels of O-GlcNAc enzymes were different in the two muscles, potentially resulting from different rates of oxidative stress and metabolic demands between the muscle types. 25416863 2 65 theme muscle 296:301 arg1 proteins 303:310 many skeletal muscle proteins 282:310 many skeletal muscle proteins 282:310 Although many skeletal muscle proteins are O-GlcNAcylated, the modification has not been extensively studied in this tissue, especially in the context of exercise. 25416863 3 66 theme O-GlcNAc 520:527 arg1 modification 537:548 O-GlcNAc protein modification 520:548 O-GlcNAc protein modification in rat skeletal muscle 520:571 This study investigated the effects of glutathione depletion and acute exercise on O-GlcNAc protein modification in rat skeletal muscle. 25416863 2 67 theme skeletal 287:294 arg1 proteins 303:310 many skeletal muscle proteins 282:310 many skeletal muscle proteins 282:310 Although many skeletal muscle proteins are O-GlcNAcylated, the modification has not been extensively studied in this tissue, especially in the context of exercise. 25416863 3 68 from effects 465:471 arg1 modification 537:548 O-GlcNAc protein modification 520:548 O-GlcNAc protein modification in rat skeletal muscle 520:571 This study investigated the effects of glutathione depletion and acute exercise on O-GlcNAc protein modification in rat skeletal muscle. 25416863 1 69 theme O-linked 167:174 arg1 β-N-acetylglucosamine 176:196 O-linked β-N-acetylglucosamine 167:196 O-linked β-N-acetylglucosamine (O-GlcNAc) 167:207 Post-translational modification of intracellular proteins with O-linked β-N-acetylglucosamine (O-GlcNAc) profoundly affects protein structure, function, and metabolism. 25416863 1 69 theme O-linked 167:174 arg1 O-GlcNAc 199:206 O-GlcNAc 199:206 O-GlcNAc 199:206 Post-translational modification of intracellular proteins with O-linked β-N-acetylglucosamine (O-GlcNAc) profoundly affects protein structure, function, and metabolism. 25416863 9 70 from muscles 1190:1196 arg1 changes 1117:1123 The changes 1113:1123 The changes in the mRNA levels of O-GlcNAc enzymes 1113:1162 The changes in the mRNA levels of O-GlcNAc enzymes were different in the two muscles, potentially resulting from different rates of oxidative stress and metabolic demands between the muscle types. 25416863 9 70 from muscles 1190:1196 arg1 different 1169:1177 different 1169:1177 different 1169:1177 The changes in the mRNA levels of O-GlcNAc enzymes were different in the two muscles, potentially resulting from different rates of oxidative stress and metabolic demands between the muscle types. 25416863 11 71 theme exercise 1611:1618 arg1 adaptation 1557:1566 cellular adaptation 1548:1566 cellular adaptation to oxidative stress 1548:1586 This could represent one mechanism underlying cellular adaptation to oxidative stress and health benefits of exercise. 25416863 11 71 theme exercise 1611:1618 arg1 benefits 1599:1606 health benefits 1592:1606 health benefits of exercise 1592:1618 This could represent one mechanism underlying cellular adaptation to oxidative stress and health benefits of exercise. 25416863 2 72 theme many 282:285 arg1 proteins 303:310 many skeletal muscle proteins 282:310 many skeletal muscle proteins 282:310 Although many skeletal muscle proteins are O-GlcNAcylated, the modification has not been extensively studied in this tissue, especially in the context of exercise. 24865644 0 0 theme prostate 83:90 arg1 cells 99:103 prostate cancer cells 83:103 prostate cancer cells 83:103 O-GlcNAcylation is increased in prostate cancer tissues and enhances malignancy of prostate cancer cells. 24865644 6 1 theme direct 897:902 arg1 evidence 904:911 direct evidence that increased O-GlcNAcylation induces malignant transformation of nontumorigenic (BPH) cells 897:1005 direct evidence that increased O-GlcNAcylation induces malignant transformation of nontumorigenic (BPH) cells 897:1005 More importantly, we provide here, for the first time to the best of our knowledge, direct evidence that increased O-GlcNAcylation induces malignant transformation of nontumorigenic (BPH) cells. 24865644 7 2 theme prostate 1151:1158 arg1 progression 1167:1177 the O-GlcNAc-induced prostate cancer progression 1130:1177 the O-GlcNAc-induced prostate cancer progression 1130:1177 Furthermore, our study suggested that inhibiting the formation of the E-cadherin/catenin/cytoskeleton complex may underly the O-GlcNAc-induced prostate cancer progression. 24865644 3 3 theme cancer 490:495 arg1 tissues 497:503 prostate cancer tissues 481:503 prostate cancer tissues 481:503 In this study, we detected the level of O-GlcNAc in prostate, liver and pancreatic cancer tissues, and found that the global O-GlcNAc modification also known as O-GlcNAcylation, is specifically increased in prostate cancer tissues compared to corresponding adjacent tissues. 24865644 6 4 theme cells 1001:1005 arg1 transformation 962:975 malignant transformation 952:975 malignant transformation of nontumorigenic (BPH) cells 952:1005 More importantly, we provide here, for the first time to the best of our knowledge, direct evidence that increased O-GlcNAcylation induces malignant transformation of nontumorigenic (BPH) cells. 24865644 2 5 from hydroxyl 186:193 arg1 proteins 264:271 numerous cytoplasmic and nuclear proteins 231:271 numerous cytoplasmic and nuclear proteins 231:271 -N-acetylglucosamine moiety attached to the side-chain hydroxyl of a serine or threonine residue in numerous cytoplasmic and nuclear proteins. 24865644 7 6 theme cancer 1160:1165 arg1 progression 1167:1177 the O-GlcNAc-induced prostate cancer progression 1130:1177 the O-GlcNAc-induced prostate cancer progression 1130:1177 Furthermore, our study suggested that inhibiting the formation of the E-cadherin/catenin/cytoskeleton complex may underly the O-GlcNAc-induced prostate cancer progression. 24865644 8 7 gly O-GlcNAcylation 1219:1233 arg1 cancer 1293:1298 pancreatic cancer 1282:1298 pancreatic cancer 1282:1298 Overall, these findings indicated that O-GlcNAcylation is increased in prostate, but not in liver and pancreatic cancer tissues, and that O-GlcNAc can enhance the malignancy of prostate cancer cells. 24865644 8 7 gly O-GlcNAcylation 1219:1233 arg1 liver 1272:1276 liver 1272:1276 liver 1272:1276 Overall, these findings indicated that O-GlcNAcylation is increased in prostate, but not in liver and pancreatic cancer tissues, and that O-GlcNAc can enhance the malignancy of prostate cancer cells. 24865644 8 7 gly O-GlcNAcylation 1219:1233 arg1 prostate 1251:1258 prostate 1251:1258 prostate 1251:1258 Overall, these findings indicated that O-GlcNAcylation is increased in prostate, but not in liver and pancreatic cancer tissues, and that O-GlcNAc can enhance the malignancy of prostate cancer cells. 24865644 6 8 theme first 856:860 arg1 time 862:865 the first time 852:865 the first time to the best of our knowledge 852:894 More importantly, we provide here, for the first time to the best of our knowledge, direct evidence that increased O-GlcNAcylation induces malignant transformation of nontumorigenic (BPH) cells. 24865644 0 9 theme cells 99:103 arg1 malignancy 69:78 malignancy 69:78 malignancy of prostate cancer cells 69:103 O-GlcNAcylation is increased in prostate cancer tissues and enhances malignancy of prostate cancer cells. 24865644 8 10 theme cells 1373:1377 arg1 malignancy 1343:1352 the malignancy 1339:1352 the malignancy of prostate cancer cells 1339:1377 Overall, these findings indicated that O-GlcNAcylation is increased in prostate, but not in liver and pancreatic cancer tissues, and that O-GlcNAc can enhance the malignancy of prostate cancer cells. 24865644 6 11 theme BPH 996:998 arg1 cells 1001:1005 nontumorigenic (BPH) cells 980:1005 nontumorigenic (BPH) cells 980:1005 More importantly, we provide here, for the first time to the best of our knowledge, direct evidence that increased O-GlcNAcylation induces malignant transformation of nontumorigenic (BPH) cells. 24865644 0 12 theme cancer 92:97 arg1 cells 99:103 prostate cancer cells 83:103 prostate cancer cells 83:103 O-GlcNAcylation is increased in prostate cancer tissues and enhances malignancy of prostate cancer cells. 24865644 7 13 theme O-GlcNAc-induced 1134:1149 arg1 progression 1167:1177 the O-GlcNAc-induced prostate cancer progression 1130:1177 the O-GlcNAc-induced prostate cancer progression 1130:1177 Furthermore, our study suggested that inhibiting the formation of the E-cadherin/catenin/cytoskeleton complex may underly the O-GlcNAc-induced prostate cancer progression. 24865644 8 14 theme cancer 1366:1371 arg1 cells 1373:1377 prostate cancer cells 1357:1377 prostate cancer cells 1357:1377 Overall, these findings indicated that O-GlcNAcylation is increased in prostate, but not in liver and pancreatic cancer tissues, and that O-GlcNAc can enhance the malignancy of prostate cancer cells. 24865644 4 15 theme epithelial 683:692 arg1 cells 694:698 benign prostatic hyperplasia (BPH) epithelial cells 648:698 benign prostatic hyperplasia (BPH) epithelial cells 648:698 In addition, we found that global O-GlcNAcylation is increased in prostate cancer cells and not in benign prostatic hyperplasia (BPH) epithelial cells. 24865644 4 16 theme global 576:581 arg1 O-GlcNAcylation 583:597 global O-GlcNAcylation 576:597 global O-GlcNAcylation 576:597 In addition, we found that global O-GlcNAcylation is increased in prostate cancer cells and not in benign prostatic hyperplasia (BPH) epithelial cells. 24865644 2 17 from threonine 210:218 arg1 proteins 264:271 numerous cytoplasmic and nuclear proteins 231:271 numerous cytoplasmic and nuclear proteins 231:271 -N-acetylglucosamine moiety attached to the side-chain hydroxyl of a serine or threonine residue in numerous cytoplasmic and nuclear proteins. 24865644 3 18 theme corresponding 517:529 arg1 tissues 540:546 corresponding adjacent tissues 517:546 corresponding adjacent tissues 517:546 In this study, we detected the level of O-GlcNAc in prostate, liver and pancreatic cancer tissues, and found that the global O-GlcNAc modification also known as O-GlcNAcylation, is specifically increased in prostate cancer tissues compared to corresponding adjacent tissues. 24865644 4 19 theme hyperplasia 665:675 arg1 cells 694:698 benign prostatic hyperplasia (BPH) epithelial cells 648:698 benign prostatic hyperplasia (BPH) epithelial cells 648:698 In addition, we found that global O-GlcNAcylation is increased in prostate cancer cells and not in benign prostatic hyperplasia (BPH) epithelial cells. 24865644 4 20 theme benign 648:653 arg1 BPH 678:680 BPH 678:680 BPH 678:680 In addition, we found that global O-GlcNAcylation is increased in prostate cancer cells and not in benign prostatic hyperplasia (BPH) epithelial cells. 24865644 4 20 theme benign 648:653 arg1 hyperplasia 665:675 benign prostatic hyperplasia 648:675 benign prostatic hyperplasia (BPH) epithelial cells 648:698 In addition, we found that global O-GlcNAcylation is increased in prostate cancer cells and not in benign prostatic hyperplasia (BPH) epithelial cells. 24865644 3 21 theme liver 336:340 arg1 tissues 364:370 prostate, liver and pancreatic cancer tissues 326:370 prostate, liver and pancreatic cancer tissues 326:370 In this study, we detected the level of O-GlcNAc in prostate, liver and pancreatic cancer tissues, and found that the global O-GlcNAc modification also known as O-GlcNAcylation, is specifically increased in prostate cancer tissues compared to corresponding adjacent tissues. 24865644 5 22 theme prostate 790:797 arg1 cells 806:810 prostate cancer cells 790:810 prostate cancer cells 790:810 O-GlcNAc enhanced the anchorage-independent growth and the migratory/invasive ability of prostate cancer cells. 24865644 3 23 theme adjacent 531:538 arg1 tissues 540:546 corresponding adjacent tissues 517:546 corresponding adjacent tissues 517:546 In this study, we detected the level of O-GlcNAc in prostate, liver and pancreatic cancer tissues, and found that the global O-GlcNAc modification also known as O-GlcNAcylation, is specifically increased in prostate cancer tissues compared to corresponding adjacent tissues. 24865644 3 24 theme O-GlcNAc 314:321 arg1 level 305:309 the level 301:309 the level of O-GlcNAc in prostate, liver and pancreatic cancer tissues 301:370 In this study, we detected the level of O-GlcNAc in prostate, liver and pancreatic cancer tissues, and found that the global O-GlcNAc modification also known as O-GlcNAcylation, is specifically increased in prostate cancer tissues compared to corresponding adjacent tissues. 24865644 2 25 theme -N-acetylglucosamine 131:150 arg1 moiety 152:157 -N-acetylglucosamine moiety 131:157 -N-acetylglucosamine moiety 131:157 -N-acetylglucosamine moiety attached to the side-chain hydroxyl of a serine or threonine residue in numerous cytoplasmic and nuclear proteins. 24865644 7 26 theme E-cadherin/catenin/cytoskeleton 1078:1108 arg1 complex 1110:1116 the E-cadherin/catenin/cytoskeleton complex 1074:1116 the E-cadherin/catenin/cytoskeleton complex 1074:1116 Furthermore, our study suggested that inhibiting the formation of the E-cadherin/catenin/cytoskeleton complex may underly the O-GlcNAc-induced prostate cancer progression. 24865644 3 27 theme O-GlcNAc 399:406 arg1 modification 408:419 the global O-GlcNAc modification 388:419 the global O-GlcNAc modification 388:419 In this study, we detected the level of O-GlcNAc in prostate, liver and pancreatic cancer tissues, and found that the global O-GlcNAc modification also known as O-GlcNAcylation, is specifically increased in prostate cancer tissues compared to corresponding adjacent tissues. 24865644 6 28 theme nontumorigenic 980:993 arg1 cells 1001:1005 nontumorigenic (BPH) cells 980:1005 nontumorigenic (BPH) cells 980:1005 More importantly, we provide here, for the first time to the best of our knowledge, direct evidence that increased O-GlcNAcylation induces malignant transformation of nontumorigenic (BPH) cells. 24865644 7 29 theme complex 1110:1116 arg1 formation 1061:1069 the formation 1057:1069 the formation of the E-cadherin/catenin/cytoskeleton complex 1057:1116 Furthermore, our study suggested that inhibiting the formation of the E-cadherin/catenin/cytoskeleton complex may underly the O-GlcNAc-induced prostate cancer progression. 24865644 4 30 theme prostatic 655:663 arg1 BPH 678:680 BPH 678:680 BPH 678:680 In addition, we found that global O-GlcNAcylation is increased in prostate cancer cells and not in benign prostatic hyperplasia (BPH) epithelial cells. 24865644 4 30 theme prostatic 655:663 arg1 hyperplasia 665:675 benign prostatic hyperplasia 648:675 benign prostatic hyperplasia (BPH) epithelial cells 648:698 In addition, we found that global O-GlcNAcylation is increased in prostate cancer cells and not in benign prostatic hyperplasia (BPH) epithelial cells. 24865644 3 31 theme cancer 357:362 arg1 tissues 364:370 prostate, liver and pancreatic cancer tissues 326:370 prostate, liver and pancreatic cancer tissues 326:370 In this study, we detected the level of O-GlcNAc in prostate, liver and pancreatic cancer tissues, and found that the global O-GlcNAc modification also known as O-GlcNAcylation, is specifically increased in prostate cancer tissues compared to corresponding adjacent tissues. 24865644 4 32 gly O-GlcNAcylation 583:597 arg1 cells 631:635 prostate cancer cells 615:635 prostate cancer cells 615:635 In addition, we found that global O-GlcNAcylation is increased in prostate cancer cells and not in benign prostatic hyperplasia (BPH) epithelial cells. 24865644 4 32 gly O-GlcNAcylation 583:597 arg1 cells 694:698 benign prostatic hyperplasia (BPH) epithelial cells 648:698 benign prostatic hyperplasia (BPH) epithelial cells 648:698 In addition, we found that global O-GlcNAcylation is increased in prostate cancer cells and not in benign prostatic hyperplasia (BPH) epithelial cells. 24865644 8 33 dep liver 1272:1276 arg1 tissues 1300:1306 tissues 1300:1306 tissues 1300:1306 Overall, these findings indicated that O-GlcNAcylation is increased in prostate, but not in liver and pancreatic cancer tissues, and that O-GlcNAc can enhance the malignancy of prostate cancer cells. 24865644 2 34 theme cytoplasmic 240:250 arg1 proteins 264:271 numerous cytoplasmic and nuclear proteins 231:271 numerous cytoplasmic and nuclear proteins 231:271 -N-acetylglucosamine moiety attached to the side-chain hydroxyl of a serine or threonine residue in numerous cytoplasmic and nuclear proteins. 24865644 4 35 theme cancer 624:629 arg1 cells 631:635 prostate cancer cells 615:635 prostate cancer cells 615:635 In addition, we found that global O-GlcNAcylation is increased in prostate cancer cells and not in benign prostatic hyperplasia (BPH) epithelial cells. 24865644 0 36 theme cancer 41:46 arg1 tissues 48:54 prostate cancer tissues 32:54 prostate cancer tissues 32:54 O-GlcNAcylation is increased in prostate cancer tissues and enhances malignancy of prostate cancer cells. 24865644 6 37 theme malignant 952:960 arg1 transformation 962:975 malignant transformation 952:975 malignant transformation of nontumorigenic (BPH) cells 952:1005 More importantly, we provide here, for the first time to the best of our knowledge, direct evidence that increased O-GlcNAcylation induces malignant transformation of nontumorigenic (BPH) cells. 24865644 0 38 gly O-GlcNAcylation 0:14 arg1 tissues 48:54 prostate cancer tissues 32:54 prostate cancer tissues 32:54 O-GlcNAcylation is increased in prostate cancer tissues and enhances malignancy of prostate cancer cells. 24865644 2 39 from proteins 264:271 arg1 hydroxyl 186:193 the side-chain hydroxyl 171:193 the side-chain hydroxyl of a serine or threonine residue in numerous cytoplasmic and nuclear proteins 171:271 -N-acetylglucosamine moiety attached to the side-chain hydroxyl of a serine or threonine residue in numerous cytoplasmic and nuclear proteins. 24865644 0 40 theme prostate 32:39 arg1 tissues 48:54 prostate cancer tissues 32:54 prostate cancer tissues 32:54 O-GlcNAcylation is increased in prostate cancer tissues and enhances malignancy of prostate cancer cells. 24865644 3 41 theme global 392:397 arg1 modification 408:419 the global O-GlcNAc modification 388:419 the global O-GlcNAc modification 388:419 In this study, we detected the level of O-GlcNAc in prostate, liver and pancreatic cancer tissues, and found that the global O-GlcNAc modification also known as O-GlcNAcylation, is specifically increased in prostate cancer tissues compared to corresponding adjacent tissues. 24865644 2 42 theme side-chain 175:184 arg1 hydroxyl 186:193 the side-chain hydroxyl 171:193 the side-chain hydroxyl of a serine or threonine residue in numerous cytoplasmic and nuclear proteins 171:271 -N-acetylglucosamine moiety attached to the side-chain hydroxyl of a serine or threonine residue in numerous cytoplasmic and nuclear proteins. 24865644 2 43 theme numerous 231:238 arg1 proteins 264:271 numerous cytoplasmic and nuclear proteins 231:271 numerous cytoplasmic and nuclear proteins 231:271 -N-acetylglucosamine moiety attached to the side-chain hydroxyl of a serine or threonine residue in numerous cytoplasmic and nuclear proteins. 24865644 5 44 theme cells 806:810 arg1 growth 745:750 the anchorage-independent growth 719:750 the anchorage-independent growth 719:750 O-GlcNAc enhanced the anchorage-independent growth and the migratory/invasive ability of prostate cancer cells. 24865644 5 44 theme cells 806:810 arg1 ability 779:785 the migratory/invasive ability 756:785 the migratory/invasive ability 756:785 O-GlcNAc enhanced the anchorage-independent growth and the migratory/invasive ability of prostate cancer cells. 24865644 2 45 from serine 200:205 arg1 proteins 264:271 numerous cytoplasmic and nuclear proteins 231:271 numerous cytoplasmic and nuclear proteins 231:271 -N-acetylglucosamine moiety attached to the side-chain hydroxyl of a serine or threonine residue in numerous cytoplasmic and nuclear proteins. 24865644 5 46 theme migratory/invasive 760:777 arg1 ability 779:785 the migratory/invasive ability 756:785 the migratory/invasive ability 756:785 O-GlcNAc enhanced the anchorage-independent growth and the migratory/invasive ability of prostate cancer cells. 24865644 2 47 attach attached 159:166 arg1 hydroxyl 186:193 the side-chain hydroxyl 171:193 the side-chain hydroxyl of a serine or threonine residue in numerous cytoplasmic and nuclear proteins 171:271 -N-acetylglucosamine moiety attached to the side-chain hydroxyl of a serine or threonine residue in numerous cytoplasmic and nuclear proteins. 24865644 2 47 attach attached 159:166 arg2 moiety 152:157 -N-acetylglucosamine moiety 131:157 -N-acetylglucosamine moiety 131:157 -N-acetylglucosamine moiety attached to the side-chain hydroxyl of a serine or threonine residue in numerous cytoplasmic and nuclear proteins. 24865644 6 48 theme increased 918:926 arg1 O-GlcNAcylation 928:942 increased O-GlcNAcylation 918:942 increased O-GlcNAcylation 918:942 More importantly, we provide here, for the first time to the best of our knowledge, direct evidence that increased O-GlcNAcylation induces malignant transformation of nontumorigenic (BPH) cells. 24865644 2 49 theme threonine 210:218 arg1 hydroxyl 186:193 the side-chain hydroxyl 171:193 the side-chain hydroxyl of a serine or threonine residue in numerous cytoplasmic and nuclear proteins 171:271 -N-acetylglucosamine moiety attached to the side-chain hydroxyl of a serine or threonine residue in numerous cytoplasmic and nuclear proteins. 24865644 3 50 theme prostate 481:488 arg1 tissues 497:503 prostate cancer tissues 481:503 prostate cancer tissues 481:503 In this study, we detected the level of O-GlcNAc in prostate, liver and pancreatic cancer tissues, and found that the global O-GlcNAc modification also known as O-GlcNAcylation, is specifically increased in prostate cancer tissues compared to corresponding adjacent tissues. 24865644 5 51 theme cancer 799:804 arg1 cells 806:810 prostate cancer cells 790:810 prostate cancer cells 790:810 O-GlcNAc enhanced the anchorage-independent growth and the migratory/invasive ability of prostate cancer cells. 24865644 8 52 theme pancreatic 1282:1291 arg1 cancer 1293:1298 pancreatic cancer 1282:1298 pancreatic cancer 1282:1298 Overall, these findings indicated that O-GlcNAcylation is increased in prostate, but not in liver and pancreatic cancer tissues, and that O-GlcNAc can enhance the malignancy of prostate cancer cells. 24865644 2 53 dep serine 200:205 arg1 residue 220:226 residue 220:226 residue 220:226 -N-acetylglucosamine moiety attached to the side-chain hydroxyl of a serine or threonine residue in numerous cytoplasmic and nuclear proteins. 24865644 2 53 dep serine 200:205 arg1 a 198:198 a 198:198 a 198:198 -N-acetylglucosamine moiety attached to the side-chain hydroxyl of a serine or threonine residue in numerous cytoplasmic and nuclear proteins. 24865644 2 54 theme serine 200:205 arg1 hydroxyl 186:193 the side-chain hydroxyl 171:193 the side-chain hydroxyl of a serine or threonine residue in numerous cytoplasmic and nuclear proteins 171:271 -N-acetylglucosamine moiety attached to the side-chain hydroxyl of a serine or threonine residue in numerous cytoplasmic and nuclear proteins. 24865644 5 55 theme anchorage-independent 723:743 arg1 growth 745:750 the anchorage-independent growth 719:750 the anchorage-independent growth 719:750 O-GlcNAc enhanced the anchorage-independent growth and the migratory/invasive ability of prostate cancer cells. 24865644 8 56 theme prostate 1357:1364 arg1 cells 1373:1377 prostate cancer cells 1357:1377 prostate cancer cells 1357:1377 Overall, these findings indicated that O-GlcNAcylation is increased in prostate, but not in liver and pancreatic cancer tissues, and that O-GlcNAc can enhance the malignancy of prostate cancer cells. 24865644 2 57 theme nuclear 256:262 arg1 proteins 264:271 numerous cytoplasmic and nuclear proteins 231:271 numerous cytoplasmic and nuclear proteins 231:271 -N-acetylglucosamine moiety attached to the side-chain hydroxyl of a serine or threonine residue in numerous cytoplasmic and nuclear proteins. 24865644 4 58 theme prostate 615:622 arg1 cells 631:635 prostate cancer cells 615:635 prostate cancer cells 615:635 In addition, we found that global O-GlcNAcylation is increased in prostate cancer cells and not in benign prostatic hyperplasia (BPH) epithelial cells. 24865644 3 59 theme prostate 326:333 arg1 tissues 364:370 prostate, liver and pancreatic cancer tissues 326:370 prostate, liver and pancreatic cancer tissues 326:370 In this study, we detected the level of O-GlcNAc in prostate, liver and pancreatic cancer tissues, and found that the global O-GlcNAc modification also known as O-GlcNAcylation, is specifically increased in prostate cancer tissues compared to corresponding adjacent tissues. 24865644 3 60 from level 305:309 arg1 tissues 364:370 prostate, liver and pancreatic cancer tissues 326:370 prostate, liver and pancreatic cancer tissues 326:370 In this study, we detected the level of O-GlcNAc in prostate, liver and pancreatic cancer tissues, and found that the global O-GlcNAc modification also known as O-GlcNAcylation, is specifically increased in prostate cancer tissues compared to corresponding adjacent tissues. 24865644 3 61 theme pancreatic 346:355 arg1 cancer 357:362 pancreatic cancer 346:362 pancreatic cancer 346:362 In this study, we detected the level of O-GlcNAc in prostate, liver and pancreatic cancer tissues, and found that the global O-GlcNAc modification also known as O-GlcNAcylation, is specifically increased in prostate cancer tissues compared to corresponding adjacent tissues. 28510447 10 0 from enrichment 1809:1818 arg1 cell 1900:1903 HeLa cell 1895:1903 HeLa cell using mass spectrometry 1895:1927 This novel immobilized triarylphosphine reagent enables efficient enrichment and sensitive detection of more than 1700 potential O-GlcNAc proteins from HeLa cell using mass spectrometry, demonstrating its potential as a general strategy for low-abundance target enrichment. 28510447 9 1 from solution 1733:1740 arg1 conjugates 1717:1726 the polymer-O-GlcNAc protein conjugates 1688:1726 the polymer-O-GlcNAc protein conjugates from solution 1688:1740 Therefore, facile sample recovery can be achieved by increasing the temperature to precipitate the polymer-O-GlcNAc protein conjugates from solution. 28510447 4 2 theme proteins 631:638 arg1 stoichiometry 605:617 the extremely low stoichiometry 587:617 the extremely low stoichiometry of O-GlcNAc proteins 587:638 Because of the extremely low stoichiometry of O-GlcNAc proteins, enrichment is required before mass spectrometry analysis for large-scale identification and in-depth understanding of their cellular function. 28510447 1 3 from modification 255:266 arg1 cells 294:298 eukaryotic cells 283:298 eukaryotic cells 283:298 O-linked β-N-acetylglucosamine (O-GlcNAc) is a ubiquitous post-translational modification of proteins in eukaryotic cells. 28510447 10 4 theme low-abundance 1984:1996 arg1 enrichment 2005:2014 low-abundance target enrichment 1984:2014 low-abundance target enrichment 1984:2014 This novel immobilized triarylphosphine reagent enables efficient enrichment and sensitive detection of more than 1700 potential O-GlcNAc proteins from HeLa cell using mass spectrometry, demonstrating its potential as a general strategy for low-abundance target enrichment. 28510447 9 5 theme sample 1611:1616 arg1 recovery 1618:1625 facile sample recovery 1604:1625 facile sample recovery 1604:1625 Therefore, facile sample recovery can be achieved by increasing the temperature to precipitate the polymer-O-GlcNAc protein conjugates from solution. 28510447 10 6 theme proteins 1881:1888 arg1 enrichment 1809:1818 efficient enrichment 1799:1818 efficient enrichment 1799:1818 This novel immobilized triarylphosphine reagent enables efficient enrichment and sensitive detection of more than 1700 potential O-GlcNAc proteins from HeLa cell using mass spectrometry, demonstrating its potential as a general strategy for low-abundance target enrichment. 28510447 10 6 theme proteins 1881:1888 arg1 detection 1834:1842 sensitive detection 1824:1842 sensitive detection 1824:1842 This novel immobilized triarylphosphine reagent enables efficient enrichment and sensitive detection of more than 1700 potential O-GlcNAc proteins from HeLa cell using mass spectrometry, demonstrating its potential as a general strategy for low-abundance target enrichment. 28510447 4 7 theme large-scale 702:712 arg1 identification 714:727 large-scale identification 702:727 large-scale identification 702:727 Because of the extremely low stoichiometry of O-GlcNAc proteins, enrichment is required before mass spectrometry analysis for large-scale identification and in-depth understanding of their cellular function. 28510447 10 8 theme triarylphosphine 1766:1781 arg1 reagent 1783:1789 This novel immobilized triarylphosphine reagent 1743:1789 This novel immobilized triarylphosphine reagent 1743:1789 This novel immobilized triarylphosphine reagent enables efficient enrichment and sensitive detection of more than 1700 potential O-GlcNAc proteins from HeLa cell using mass spectrometry, demonstrating its potential as a general strategy for low-abundance target enrichment. 28510447 7 9 theme O-GlcNAc 1242:1249 arg1 proteins 1251:1258 azide-labeled O-GlcNAc proteins 1228:1258 azide-labeled O-GlcNAc proteins 1228:1258 As a result, facilitated coupling is achieved between triarylphosphine and azide-labeled O-GlcNAc proteins via Staudinger ligation, due to the increased triarylphosphine concentration, reduced interfacial mass transfer resistance, and steric hindrance in homogeneous reaction. 28510447 2 10 theme low 315:317 arg1 abundance 319:327 their low abundance 309:327 their low abundance 309:327 Despite their low abundance, O-GlcNAc-modified proteins play many important roles in regulating gene expression, signal transduction, and cell cycle. 28510447 5 11 theme azide-labeled 936:948 arg1 proteins 959:966 azide-labeled O-GlcNAc proteins 936:966 azide-labeled O-GlcNAc proteins from complex biological samples 936:998 In this work, we designed and synthesized a novel thermosensitive immobilized triarylphosphine reagent as a convenient tool for efficient enrichment of azide-labeled O-GlcNAc proteins from complex biological samples. 28510447 10 12 theme sensitive 1824:1832 arg1 detection 1834:1842 sensitive detection 1824:1842 sensitive detection 1824:1842 This novel immobilized triarylphosphine reagent enables efficient enrichment and sensitive detection of more than 1700 potential O-GlcNAc proteins from HeLa cell using mass spectrometry, demonstrating its potential as a general strategy for low-abundance target enrichment. 28510447 2 13 theme many 362:365 arg1 roles 377:381 many important roles 362:381 many important roles 362:381 Despite their low abundance, O-GlcNAc-modified proteins play many important roles in regulating gene expression, signal transduction, and cell cycle. 28510447 5 14 theme proteins 959:966 arg1 enrichment 922:931 efficient enrichment 912:931 efficient enrichment of azide-labeled O-GlcNAc proteins from complex biological samples 912:998 In this work, we designed and synthesized a novel thermosensitive immobilized triarylphosphine reagent as a convenient tool for efficient enrichment of azide-labeled O-GlcNAc proteins from complex biological samples. 28510447 4 15 theme mass 671:674 arg1 analysis 689:696 mass spectrometry analysis 671:696 mass spectrometry analysis 671:696 Because of the extremely low stoichiometry of O-GlcNAc proteins, enrichment is required before mass spectrometry analysis for large-scale identification and in-depth understanding of their cellular function. 28510447 0 16 theme O-GlcNAc 138:145 arg1 Proteins 147:154 O-GlcNAc Proteins 138:154 O-GlcNAc Proteins 138:154 Synthesis of a Highly Azide-Reactive and Thermosensitive Biofunctional Reagent for Efficient Enrichment and Large-Scale Identification of O-GlcNAc Proteins by Mass Spectrometry. 28510447 1 17 theme ubiquitous 225:234 arg1 β-N-acetylglucosamine 187:207 O-linked β-N-acetylglucosamine 178:207 O-linked β-N-acetylglucosamine (O-GlcNAc) 178:218 O-linked β-N-acetylglucosamine (O-GlcNAc) is a ubiquitous post-translational modification of proteins in eukaryotic cells. 28510447 1 17 theme ubiquitous 225:234 arg1 modification 255:266 a ubiquitous post-translational modification 223:266 a ubiquitous post-translational modification of proteins in eukaryotic cells 223:298 O-linked β-N-acetylglucosamine (O-GlcNAc) is a ubiquitous post-translational modification of proteins in eukaryotic cells. 28510447 6 18 theme water-soluble 1046:1058 arg1 polymer 1076:1082 highly water-soluble thermosensitive polymer 1039:1082 highly water-soluble thermosensitive polymer 1039:1082 Immobilization of triarylphosphine on highly water-soluble thermosensitive polymer largely increases its solubility and reactivity in aqueous solution. 28510447 4 19 theme function 774:781 arg1 identification 714:727 large-scale identification 702:727 large-scale identification 702:727 Because of the extremely low stoichiometry of O-GlcNAc proteins, enrichment is required before mass spectrometry analysis for large-scale identification and in-depth understanding of their cellular function. 28510447 4 19 theme function 774:781 arg1 understanding 742:754 in-depth understanding 733:754 in-depth understanding of their cellular function 733:781 Because of the extremely low stoichiometry of O-GlcNAc proteins, enrichment is required before mass spectrometry analysis for large-scale identification and in-depth understanding of their cellular function. 28510447 7 20 theme facilitated 1166:1176 arg1 result 1158:1163 a result 1156:1163 a result 1156:1163 As a result, facilitated coupling is achieved between triarylphosphine and azide-labeled O-GlcNAc proteins via Staudinger ligation, due to the increased triarylphosphine concentration, reduced interfacial mass transfer resistance, and steric hindrance in homogeneous reaction. 28510447 7 20 theme facilitated 1166:1176 arg1 coupling 1178:1185 facilitated coupling 1166:1185 facilitated coupling 1166:1185 As a result, facilitated coupling is achieved between triarylphosphine and azide-labeled O-GlcNAc proteins via Staudinger ligation, due to the increased triarylphosphine concentration, reduced interfacial mass transfer resistance, and steric hindrance in homogeneous reaction. 28510447 7 21 theme due 1285:1287 arg1 ligation 1275:1282 Staudinger ligation 1264:1282 Staudinger ligation 1264:1282 As a result, facilitated coupling is achieved between triarylphosphine and azide-labeled O-GlcNAc proteins via Staudinger ligation, due to the increased triarylphosphine concentration, reduced interfacial mass transfer resistance, and steric hindrance in homogeneous reaction. 28510447 10 22 theme target 1998:2003 arg1 enrichment 2005:2014 low-abundance target enrichment 1984:2014 low-abundance target enrichment 1984:2014 This novel immobilized triarylphosphine reagent enables efficient enrichment and sensitive detection of more than 1700 potential O-GlcNAc proteins from HeLa cell using mass spectrometry, demonstrating its potential as a general strategy for low-abundance target enrichment. 28510447 9 23 theme polymer-O-GlcNAc 1692:1707 arg1 conjugates 1717:1726 the polymer-O-GlcNAc protein conjugates 1688:1726 the polymer-O-GlcNAc protein conjugates from solution 1688:1740 Therefore, facile sample recovery can be achieved by increasing the temperature to precipitate the polymer-O-GlcNAc protein conjugates from solution. 28510447 7 24 theme steric 1388:1393 arg1 hindrance 1395:1403 steric hindrance 1388:1403 steric hindrance 1388:1403 As a result, facilitated coupling is achieved between triarylphosphine and azide-labeled O-GlcNAc proteins via Staudinger ligation, due to the increased triarylphosphine concentration, reduced interfacial mass transfer resistance, and steric hindrance in homogeneous reaction. 28510447 5 25 theme convenient 892:901 arg1 tool 903:906 a convenient tool 890:906 a convenient tool for efficient enrichment of azide-labeled O-GlcNAc proteins from complex biological samples 890:998 In this work, we designed and synthesized a novel thermosensitive immobilized triarylphosphine reagent as a convenient tool for efficient enrichment of azide-labeled O-GlcNAc proteins from complex biological samples. 28510447 5 25 theme convenient 892:901 arg1 reagent 879:885 a novel thermosensitive immobilized triarylphosphine reagent 826:885 a novel thermosensitive immobilized triarylphosphine reagent 826:885 In this work, we designed and synthesized a novel thermosensitive immobilized triarylphosphine reagent as a convenient tool for efficient enrichment of azide-labeled O-GlcNAc proteins from complex biological samples. 28510447 5 26 theme complex 973:979 arg1 samples 992:998 complex biological samples 973:998 complex biological samples 973:998 In this work, we designed and synthesized a novel thermosensitive immobilized triarylphosphine reagent as a convenient tool for efficient enrichment of azide-labeled O-GlcNAc proteins from complex biological samples. 28510447 6 27 theme aqueous 1135:1141 arg1 solution 1143:1150 aqueous solution 1135:1150 aqueous solution 1135:1150 Immobilization of triarylphosphine on highly water-soluble thermosensitive polymer largely increases its solubility and reactivity in aqueous solution. 28510447 8 28 theme full 1498:1501 arg1 precipitation 1503:1515 full precipitation 1498:1515 full precipitation 1498:1515 Furthermore, solubility of the polymer from complete dissolution to full precipitation can be easily controlled by simply adjusting the environmental temperature. 28510447 0 29 theme Efficient 83:91 arg1 Enrichment 93:102 Efficient Enrichment 83:102 Efficient Enrichment 83:102 Synthesis of a Highly Azide-Reactive and Thermosensitive Biofunctional Reagent for Efficient Enrichment and Large-Scale Identification of O-GlcNAc Proteins by Mass Spectrometry. 28510447 7 30 theme transfer 1363:1370 arg1 resistance 1372:1381 reduced interfacial mass transfer resistance 1338:1381 reduced interfacial mass transfer resistance 1338:1381 As a result, facilitated coupling is achieved between triarylphosphine and azide-labeled O-GlcNAc proteins via Staudinger ligation, due to the increased triarylphosphine concentration, reduced interfacial mass transfer resistance, and steric hindrance in homogeneous reaction. 28510447 7 31 theme interfacial 1346:1356 arg1 resistance 1372:1381 reduced interfacial mass transfer resistance 1338:1381 reduced interfacial mass transfer resistance 1338:1381 As a result, facilitated coupling is achieved between triarylphosphine and azide-labeled O-GlcNAc proteins via Staudinger ligation, due to the increased triarylphosphine concentration, reduced interfacial mass transfer resistance, and steric hindrance in homogeneous reaction. 28510447 10 32 theme O-GlcNAc 1872:1879 arg1 proteins 1881:1888 more than 1700 potential O-GlcNAc proteins 1847:1888 more than 1700 potential O-GlcNAc proteins from HeLa cell using mass spectrometry 1847:1927 This novel immobilized triarylphosphine reagent enables efficient enrichment and sensitive detection of more than 1700 potential O-GlcNAc proteins from HeLa cell using mass spectrometry, demonstrating its potential as a general strategy for low-abundance target enrichment. 28510447 8 33 from dissolution 1483:1493 arg1 solubility 1443:1452 solubility 1443:1452 solubility of the polymer from complete dissolution to full precipitation 1443:1515 Furthermore, solubility of the polymer from complete dissolution to full precipitation can be easily controlled by simply adjusting the environmental temperature. 28510447 1 34 link O-linked 178:185 arg1 modification 255:266 a ubiquitous post-translational modification 223:266 a ubiquitous post-translational modification of proteins in eukaryotic cells 223:298 O-linked β-N-acetylglucosamine (O-GlcNAc) is a ubiquitous post-translational modification of proteins in eukaryotic cells. 28510447 1 34 link O-linked 178:185 arg1 O-GlcNAc 210:217 O-GlcNAc 210:217 O-GlcNAc 210:217 O-linked β-N-acetylglucosamine (O-GlcNAc) is a ubiquitous post-translational modification of proteins in eukaryotic cells. 28510447 1 34 link O-linked 178:185 arg1 β-N-acetylglucosamine 187:207 O-linked β-N-acetylglucosamine 178:207 O-linked β-N-acetylglucosamine (O-GlcNAc) 178:218 O-linked β-N-acetylglucosamine (O-GlcNAc) is a ubiquitous post-translational modification of proteins in eukaryotic cells. 28510447 10 35 theme mass 1911:1914 arg1 spectrometry 1916:1927 mass spectrometry 1911:1927 mass spectrometry 1911:1927 This novel immobilized triarylphosphine reagent enables efficient enrichment and sensitive detection of more than 1700 potential O-GlcNAc proteins from HeLa cell using mass spectrometry, demonstrating its potential as a general strategy for low-abundance target enrichment. 28510447 7 36 theme triarylphosphine 1306:1321 arg1 concentration 1323:1335 the increased triarylphosphine concentration 1292:1335 the increased triarylphosphine concentration 1292:1335 As a result, facilitated coupling is achieved between triarylphosphine and azide-labeled O-GlcNAc proteins via Staudinger ligation, due to the increased triarylphosphine concentration, reduced interfacial mass transfer resistance, and steric hindrance in homogeneous reaction. 28510447 3 37 theme O-GlcNAc 460:467 arg1 proteins 469:476 Aberrant O-GlcNAc proteins 451:476 Aberrant O-GlcNAc proteins 451:476 Aberrant O-GlcNAc proteins are correlated with many major human diseases, such as Alzheimer's disease, diabetes, and cancer. 28510447 8 38 theme environmental 1566:1578 arg1 temperature 1580:1590 the environmental temperature 1562:1590 the environmental temperature 1562:1590 Furthermore, solubility of the polymer from complete dissolution to full precipitation can be easily controlled by simply adjusting the environmental temperature. 28510447 3 39 theme major 503:507 arg1 diabetes 554:561 diabetes 554:561 diabetes 554:561 Aberrant O-GlcNAc proteins are correlated with many major human diseases, such as Alzheimer's disease, diabetes, and cancer. 28510447 3 39 theme major 503:507 arg1 diseases 515:522 many major human diseases 498:522 many major human diseases 498:522 Aberrant O-GlcNAc proteins are correlated with many major human diseases, such as Alzheimer's disease, diabetes, and cancer. 28510447 3 39 theme major 503:507 arg1 cancer 568:573 cancer 568:573 cancer 568:573 Aberrant O-GlcNAc proteins are correlated with many major human diseases, such as Alzheimer's disease, diabetes, and cancer. 28510447 3 39 theme major 503:507 arg1 disease 545:551 Alzheimer's disease 533:551 Alzheimer's disease 533:551 Aberrant O-GlcNAc proteins are correlated with many major human diseases, such as Alzheimer's disease, diabetes, and cancer. 28510447 0 40 theme Azide-Reactive 22:35 arg1 Reagent 71:77 a Highly Azide-Reactive and Thermosensitive Biofunctional Reagent 13:77 a Highly Azide-Reactive and Thermosensitive Biofunctional Reagent for Efficient Enrichment and Large-Scale Identification of O-GlcNAc Proteins 13:154 Synthesis of a Highly Azide-Reactive and Thermosensitive Biofunctional Reagent for Efficient Enrichment and Large-Scale Identification of O-GlcNAc Proteins by Mass Spectrometry. 28510447 5 41 theme thermosensitive 834:848 arg1 tool 903:906 a convenient tool 890:906 a convenient tool for efficient enrichment of azide-labeled O-GlcNAc proteins from complex biological samples 890:998 In this work, we designed and synthesized a novel thermosensitive immobilized triarylphosphine reagent as a convenient tool for efficient enrichment of azide-labeled O-GlcNAc proteins from complex biological samples. 28510447 5 41 theme thermosensitive 834:848 arg1 reagent 879:885 a novel thermosensitive immobilized triarylphosphine reagent 826:885 a novel thermosensitive immobilized triarylphosphine reagent 826:885 In this work, we designed and synthesized a novel thermosensitive immobilized triarylphosphine reagent as a convenient tool for efficient enrichment of azide-labeled O-GlcNAc proteins from complex biological samples. 28510447 0 42 theme Reagent 71:77 arg1 Synthesis 0:8 Synthesis 0:8 Synthesis of a Highly Azide-Reactive and Thermosensitive Biofunctional Reagent for Efficient Enrichment and Large-Scale Identification of O-GlcNAc Proteins by Mass Spectrometry. 0:176 Synthesis of a Highly Azide-Reactive and Thermosensitive Biofunctional Reagent for Efficient Enrichment and Large-Scale Identification of O-GlcNAc Proteins by Mass Spectrometry. 28510447 2 43 theme gene 397:400 arg1 expression 402:411 gene expression 397:411 gene expression 397:411 Despite their low abundance, O-GlcNAc-modified proteins play many important roles in regulating gene expression, signal transduction, and cell cycle. 28510447 5 44 theme triarylphosphine 862:877 arg1 tool 903:906 a convenient tool 890:906 a convenient tool for efficient enrichment of azide-labeled O-GlcNAc proteins from complex biological samples 890:998 In this work, we designed and synthesized a novel thermosensitive immobilized triarylphosphine reagent as a convenient tool for efficient enrichment of azide-labeled O-GlcNAc proteins from complex biological samples. 28510447 5 44 theme triarylphosphine 862:877 arg1 reagent 879:885 a novel thermosensitive immobilized triarylphosphine reagent 826:885 a novel thermosensitive immobilized triarylphosphine reagent 826:885 In this work, we designed and synthesized a novel thermosensitive immobilized triarylphosphine reagent as a convenient tool for efficient enrichment of azide-labeled O-GlcNAc proteins from complex biological samples. 28510447 10 45 from cell 1900:1903 arg1 proteins 1881:1888 more than 1700 potential O-GlcNAc proteins 1847:1888 more than 1700 potential O-GlcNAc proteins from HeLa cell using mass spectrometry 1847:1927 This novel immobilized triarylphosphine reagent enables efficient enrichment and sensitive detection of more than 1700 potential O-GlcNAc proteins from HeLa cell using mass spectrometry, demonstrating its potential as a general strategy for low-abundance target enrichment. 28510447 10 45 from cell 1900:1903 arg1 enrichment 1809:1818 efficient enrichment 1799:1818 efficient enrichment 1799:1818 This novel immobilized triarylphosphine reagent enables efficient enrichment and sensitive detection of more than 1700 potential O-GlcNAc proteins from HeLa cell using mass spectrometry, demonstrating its potential as a general strategy for low-abundance target enrichment. 28510447 10 45 from cell 1900:1903 arg1 detection 1834:1842 sensitive detection 1824:1842 sensitive detection 1824:1842 This novel immobilized triarylphosphine reagent enables efficient enrichment and sensitive detection of more than 1700 potential O-GlcNAc proteins from HeLa cell using mass spectrometry, demonstrating its potential as a general strategy for low-abundance target enrichment. 28510447 4 46 theme in-depth 733:740 arg1 understanding 742:754 in-depth understanding 733:754 in-depth understanding of their cellular function 733:781 Because of the extremely low stoichiometry of O-GlcNAc proteins, enrichment is required before mass spectrometry analysis for large-scale identification and in-depth understanding of their cellular function. 28510447 6 47 from Immobilization 1001:1014 arg1 polymer 1076:1082 highly water-soluble thermosensitive polymer 1039:1082 highly water-soluble thermosensitive polymer 1039:1082 Immobilization of triarylphosphine on highly water-soluble thermosensitive polymer largely increases its solubility and reactivity in aqueous solution. 28510447 10 48 theme HeLa 1895:1898 arg1 cell 1900:1903 HeLa cell 1895:1903 HeLa cell using mass spectrometry 1895:1927 This novel immobilized triarylphosphine reagent enables efficient enrichment and sensitive detection of more than 1700 potential O-GlcNAc proteins from HeLa cell using mass spectrometry, demonstrating its potential as a general strategy for low-abundance target enrichment. 28510447 10 49 theme general 1963:1969 arg1 strategy 1971:1978 a general strategy 1961:1978 a general strategy for low-abundance target enrichment 1961:2014 This novel immobilized triarylphosphine reagent enables efficient enrichment and sensitive detection of more than 1700 potential O-GlcNAc proteins from HeLa cell using mass spectrometry, demonstrating its potential as a general strategy for low-abundance target enrichment. 28510447 10 49 theme general 1963:1969 arg1 potential 1948:1956 its potential 1944:1956 its potential 1944:1956 This novel immobilized triarylphosphine reagent enables efficient enrichment and sensitive detection of more than 1700 potential O-GlcNAc proteins from HeLa cell using mass spectrometry, demonstrating its potential as a general strategy for low-abundance target enrichment. 28510447 0 50 theme Biofunctional 57:69 arg1 Reagent 71:77 a Highly Azide-Reactive and Thermosensitive Biofunctional Reagent 13:77 a Highly Azide-Reactive and Thermosensitive Biofunctional Reagent for Efficient Enrichment and Large-Scale Identification of O-GlcNAc Proteins 13:154 Synthesis of a Highly Azide-Reactive and Thermosensitive Biofunctional Reagent for Efficient Enrichment and Large-Scale Identification of O-GlcNAc Proteins by Mass Spectrometry. 28510447 6 51 theme triarylphosphine 1019:1034 arg1 Immobilization 1001:1014 Immobilization 1001:1014 Immobilization of triarylphosphine on highly water-soluble thermosensitive polymer 1001:1082 Immobilization of triarylphosphine on highly water-soluble thermosensitive polymer largely increases its solubility and reactivity in aqueous solution. 28510447 7 52 theme Staudinger 1264:1273 arg1 ligation 1275:1282 Staudinger ligation 1264:1282 Staudinger ligation 1264:1282 As a result, facilitated coupling is achieved between triarylphosphine and azide-labeled O-GlcNAc proteins via Staudinger ligation, due to the increased triarylphosphine concentration, reduced interfacial mass transfer resistance, and steric hindrance in homogeneous reaction. 28510447 10 53 from detection 1834:1842 arg1 cell 1900:1903 HeLa cell 1895:1903 HeLa cell using mass spectrometry 1895:1927 This novel immobilized triarylphosphine reagent enables efficient enrichment and sensitive detection of more than 1700 potential O-GlcNAc proteins from HeLa cell using mass spectrometry, demonstrating its potential as a general strategy for low-abundance target enrichment. 28510447 7 54 from hindrance 1395:1403 arg1 reaction 1420:1427 homogeneous reaction 1408:1427 homogeneous reaction 1408:1427 As a result, facilitated coupling is achieved between triarylphosphine and azide-labeled O-GlcNAc proteins via Staudinger ligation, due to the increased triarylphosphine concentration, reduced interfacial mass transfer resistance, and steric hindrance in homogeneous reaction. 28510447 10 55 theme efficient 1799:1807 arg1 enrichment 1809:1818 efficient enrichment 1799:1818 efficient enrichment 1799:1818 This novel immobilized triarylphosphine reagent enables efficient enrichment and sensitive detection of more than 1700 potential O-GlcNAc proteins from HeLa cell using mass spectrometry, demonstrating its potential as a general strategy for low-abundance target enrichment. 28510447 2 56 theme O-GlcNAc-modified 330:346 arg1 proteins 348:355 O-GlcNAc-modified proteins 330:355 O-GlcNAc-modified proteins 330:355 Despite their low abundance, O-GlcNAc-modified proteins play many important roles in regulating gene expression, signal transduction, and cell cycle. 28510447 9 57 theme facile 1604:1609 arg1 recovery 1618:1625 facile sample recovery 1604:1625 facile sample recovery 1604:1625 Therefore, facile sample recovery can be achieved by increasing the temperature to precipitate the polymer-O-GlcNAc protein conjugates from solution. 28510447 5 58 theme biological 981:990 arg1 samples 992:998 complex biological samples 973:998 complex biological samples 973:998 In this work, we designed and synthesized a novel thermosensitive immobilized triarylphosphine reagent as a convenient tool for efficient enrichment of azide-labeled O-GlcNAc proteins from complex biological samples. 28510447 4 59 theme O-GlcNAc 622:629 arg1 proteins 631:638 O-GlcNAc proteins 622:638 O-GlcNAc proteins 622:638 Because of the extremely low stoichiometry of O-GlcNAc proteins, enrichment is required before mass spectrometry analysis for large-scale identification and in-depth understanding of their cellular function. 28510447 7 60 theme azide-labeled 1228:1240 arg1 proteins 1251:1258 azide-labeled O-GlcNAc proteins 1228:1258 azide-labeled O-GlcNAc proteins 1228:1258 As a result, facilitated coupling is achieved between triarylphosphine and azide-labeled O-GlcNAc proteins via Staudinger ligation, due to the increased triarylphosphine concentration, reduced interfacial mass transfer resistance, and steric hindrance in homogeneous reaction. 28510447 0 61 theme Thermosensitive 41:55 arg1 Reagent 71:77 a Highly Azide-Reactive and Thermosensitive Biofunctional Reagent 13:77 a Highly Azide-Reactive and Thermosensitive Biofunctional Reagent for Efficient Enrichment and Large-Scale Identification of O-GlcNAc Proteins 13:154 Synthesis of a Highly Azide-Reactive and Thermosensitive Biofunctional Reagent for Efficient Enrichment and Large-Scale Identification of O-GlcNAc Proteins by Mass Spectrometry. 28510447 2 62 theme important 367:375 arg1 roles 377:381 many important roles 362:381 many important roles 362:381 Despite their low abundance, O-GlcNAc-modified proteins play many important roles in regulating gene expression, signal transduction, and cell cycle. 28510447 5 63 theme O-GlcNAc 950:957 arg1 proteins 959:966 azide-labeled O-GlcNAc proteins 936:966 azide-labeled O-GlcNAc proteins from complex biological samples 936:998 In this work, we designed and synthesized a novel thermosensitive immobilized triarylphosphine reagent as a convenient tool for efficient enrichment of azide-labeled O-GlcNAc proteins from complex biological samples. 28510447 0 64 theme Proteins 147:154 arg1 Enrichment 93:102 Efficient Enrichment 83:102 Efficient Enrichment 83:102 Synthesis of a Highly Azide-Reactive and Thermosensitive Biofunctional Reagent for Efficient Enrichment and Large-Scale Identification of O-GlcNAc Proteins by Mass Spectrometry. 28510447 0 64 theme Proteins 147:154 arg1 Identification 120:133 Large-Scale Identification 108:133 Large-Scale Identification 108:133 Synthesis of a Highly Azide-Reactive and Thermosensitive Biofunctional Reagent for Efficient Enrichment and Large-Scale Identification of O-GlcNAc Proteins by Mass Spectrometry. 28510447 0 65 theme Mass 159:162 arg1 Spectrometry 164:175 Mass Spectrometry 159:175 Mass Spectrometry 159:175 Synthesis of a Highly Azide-Reactive and Thermosensitive Biofunctional Reagent for Efficient Enrichment and Large-Scale Identification of O-GlcNAc Proteins by Mass Spectrometry. 28510447 5 66 theme efficient 912:920 arg1 enrichment 922:931 efficient enrichment 912:931 efficient enrichment of azide-labeled O-GlcNAc proteins from complex biological samples 912:998 In this work, we designed and synthesized a novel thermosensitive immobilized triarylphosphine reagent as a convenient tool for efficient enrichment of azide-labeled O-GlcNAc proteins from complex biological samples. 28510447 6 67 theme thermosensitive 1060:1074 arg1 polymer 1076:1082 highly water-soluble thermosensitive polymer 1039:1082 highly water-soluble thermosensitive polymer 1039:1082 Immobilization of triarylphosphine on highly water-soluble thermosensitive polymer largely increases its solubility and reactivity in aqueous solution. 28510447 4 68 theme spectrometry 676:687 arg1 analysis 689:696 mass spectrometry analysis 671:696 mass spectrometry analysis 671:696 Because of the extremely low stoichiometry of O-GlcNAc proteins, enrichment is required before mass spectrometry analysis for large-scale identification and in-depth understanding of their cellular function. 28510447 7 69 theme mass 1358:1361 arg1 resistance 1372:1381 reduced interfacial mass transfer resistance 1338:1381 reduced interfacial mass transfer resistance 1338:1381 As a result, facilitated coupling is achieved between triarylphosphine and azide-labeled O-GlcNAc proteins via Staudinger ligation, due to the increased triarylphosphine concentration, reduced interfacial mass transfer resistance, and steric hindrance in homogeneous reaction. 28510447 5 70 from enrichment 922:931 arg1 samples 992:998 complex biological samples 973:998 complex biological samples 973:998 In this work, we designed and synthesized a novel thermosensitive immobilized triarylphosphine reagent as a convenient tool for efficient enrichment of azide-labeled O-GlcNAc proteins from complex biological samples. 28510447 7 71 from resistance 1372:1381 arg1 reaction 1420:1427 homogeneous reaction 1408:1427 homogeneous reaction 1408:1427 As a result, facilitated coupling is achieved between triarylphosphine and azide-labeled O-GlcNAc proteins via Staudinger ligation, due to the increased triarylphosphine concentration, reduced interfacial mass transfer resistance, and steric hindrance in homogeneous reaction. 28510447 4 72 theme cellular 765:772 arg1 function 774:781 their cellular function 759:781 their cellular function 759:781 Because of the extremely low stoichiometry of O-GlcNAc proteins, enrichment is required before mass spectrometry analysis for large-scale identification and in-depth understanding of their cellular function. 28510447 8 73 theme polymer 1461:1467 arg1 solubility 1443:1452 solubility 1443:1452 solubility of the polymer from complete dissolution to full precipitation 1443:1515 Furthermore, solubility of the polymer from complete dissolution to full precipitation can be easily controlled by simply adjusting the environmental temperature. 28510447 9 74 theme protein 1709:1715 arg1 conjugates 1717:1726 the polymer-O-GlcNAc protein conjugates 1688:1726 the polymer-O-GlcNAc protein conjugates from solution 1688:1740 Therefore, facile sample recovery can be achieved by increasing the temperature to precipitate the polymer-O-GlcNAc protein conjugates from solution. 28510447 8 75 theme complete 1474:1481 arg1 dissolution 1483:1493 complete dissolution 1474:1493 complete dissolution to full precipitation 1474:1515 Furthermore, solubility of the polymer from complete dissolution to full precipitation can be easily controlled by simply adjusting the environmental temperature. 28510447 1 76 theme O-linked 178:185 arg1 modification 255:266 a ubiquitous post-translational modification 223:266 a ubiquitous post-translational modification of proteins in eukaryotic cells 223:298 O-linked β-N-acetylglucosamine (O-GlcNAc) is a ubiquitous post-translational modification of proteins in eukaryotic cells. 28510447 1 76 theme O-linked 178:185 arg1 O-GlcNAc 210:217 O-GlcNAc 210:217 O-GlcNAc 210:217 O-linked β-N-acetylglucosamine (O-GlcNAc) is a ubiquitous post-translational modification of proteins in eukaryotic cells. 28510447 1 76 theme O-linked 178:185 arg1 β-N-acetylglucosamine 187:207 O-linked β-N-acetylglucosamine 178:207 O-linked β-N-acetylglucosamine (O-GlcNAc) 178:218 O-linked β-N-acetylglucosamine (O-GlcNAc) is a ubiquitous post-translational modification of proteins in eukaryotic cells. 28510447 0 77 theme Large-Scale 108:118 arg1 Identification 120:133 Large-Scale Identification 108:133 Large-Scale Identification 108:133 Synthesis of a Highly Azide-Reactive and Thermosensitive Biofunctional Reagent for Efficient Enrichment and Large-Scale Identification of O-GlcNAc Proteins by Mass Spectrometry. 28510447 5 78 from samples 992:998 arg1 enrichment 922:931 efficient enrichment 912:931 efficient enrichment of azide-labeled O-GlcNAc proteins from complex biological samples 912:998 In this work, we designed and synthesized a novel thermosensitive immobilized triarylphosphine reagent as a convenient tool for efficient enrichment of azide-labeled O-GlcNAc proteins from complex biological samples. 28510447 5 78 from samples 992:998 arg1 proteins 959:966 azide-labeled O-GlcNAc proteins 936:966 azide-labeled O-GlcNAc proteins from complex biological samples 936:998 In this work, we designed and synthesized a novel thermosensitive immobilized triarylphosphine reagent as a convenient tool for efficient enrichment of azide-labeled O-GlcNAc proteins from complex biological samples. 28510447 7 79 theme reduced 1338:1344 arg1 resistance 1372:1381 reduced interfacial mass transfer resistance 1338:1381 reduced interfacial mass transfer resistance 1338:1381 As a result, facilitated coupling is achieved between triarylphosphine and azide-labeled O-GlcNAc proteins via Staudinger ligation, due to the increased triarylphosphine concentration, reduced interfacial mass transfer resistance, and steric hindrance in homogeneous reaction. 28510447 7 80 from concentration 1323:1335 arg1 reaction 1420:1427 homogeneous reaction 1408:1427 homogeneous reaction 1408:1427 As a result, facilitated coupling is achieved between triarylphosphine and azide-labeled O-GlcNAc proteins via Staudinger ligation, due to the increased triarylphosphine concentration, reduced interfacial mass transfer resistance, and steric hindrance in homogeneous reaction. 28510447 6 81 from solubility 1106:1115 arg1 solution 1143:1150 aqueous solution 1135:1150 aqueous solution 1135:1150 Immobilization of triarylphosphine on highly water-soluble thermosensitive polymer largely increases its solubility and reactivity in aqueous solution. 28510447 2 82 theme cell 439:442 arg1 cycle 444:448 cell cycle 439:448 cell cycle 439:448 Despite their low abundance, O-GlcNAc-modified proteins play many important roles in regulating gene expression, signal transduction, and cell cycle. 28510447 10 83 theme immobilized 1754:1764 arg1 reagent 1783:1789 This novel immobilized triarylphosphine reagent 1743:1789 This novel immobilized triarylphosphine reagent 1743:1789 This novel immobilized triarylphosphine reagent enables efficient enrichment and sensitive detection of more than 1700 potential O-GlcNAc proteins from HeLa cell using mass spectrometry, demonstrating its potential as a general strategy for low-abundance target enrichment. 28510447 6 84 from reactivity 1121:1130 arg1 solution 1143:1150 aqueous solution 1135:1150 aqueous solution 1135:1150 Immobilization of triarylphosphine on highly water-soluble thermosensitive polymer largely increases its solubility and reactivity in aqueous solution. 28510447 10 85 theme potential 1862:1870 arg1 proteins 1881:1888 more than 1700 potential O-GlcNAc proteins 1847:1888 more than 1700 potential O-GlcNAc proteins from HeLa cell using mass spectrometry 1847:1927 This novel immobilized triarylphosphine reagent enables efficient enrichment and sensitive detection of more than 1700 potential O-GlcNAc proteins from HeLa cell using mass spectrometry, demonstrating its potential as a general strategy for low-abundance target enrichment. 28510447 7 86 theme increased 1296:1304 arg1 concentration 1323:1335 the increased triarylphosphine concentration 1292:1335 the increased triarylphosphine concentration 1292:1335 As a result, facilitated coupling is achieved between triarylphosphine and azide-labeled O-GlcNAc proteins via Staudinger ligation, due to the increased triarylphosphine concentration, reduced interfacial mass transfer resistance, and steric hindrance in homogeneous reaction. 28510447 4 87 theme low 601:603 arg1 stoichiometry 605:617 the extremely low stoichiometry 587:617 the extremely low stoichiometry of O-GlcNAc proteins 587:638 Because of the extremely low stoichiometry of O-GlcNAc proteins, enrichment is required before mass spectrometry analysis for large-scale identification and in-depth understanding of their cellular function. 28510447 5 88 theme novel 828:832 arg1 tool 903:906 a convenient tool 890:906 a convenient tool for efficient enrichment of azide-labeled O-GlcNAc proteins from complex biological samples 890:998 In this work, we designed and synthesized a novel thermosensitive immobilized triarylphosphine reagent as a convenient tool for efficient enrichment of azide-labeled O-GlcNAc proteins from complex biological samples. 28510447 5 88 theme novel 828:832 arg1 reagent 879:885 a novel thermosensitive immobilized triarylphosphine reagent 826:885 a novel thermosensitive immobilized triarylphosphine reagent 826:885 In this work, we designed and synthesized a novel thermosensitive immobilized triarylphosphine reagent as a convenient tool for efficient enrichment of azide-labeled O-GlcNAc proteins from complex biological samples. 28510447 1 89 theme post-translational 236:253 arg1 β-N-acetylglucosamine 187:207 O-linked β-N-acetylglucosamine 178:207 O-linked β-N-acetylglucosamine (O-GlcNAc) 178:218 O-linked β-N-acetylglucosamine (O-GlcNAc) is a ubiquitous post-translational modification of proteins in eukaryotic cells. 28510447 1 89 theme post-translational 236:253 arg1 modification 255:266 a ubiquitous post-translational modification 223:266 a ubiquitous post-translational modification of proteins in eukaryotic cells 223:298 O-linked β-N-acetylglucosamine (O-GlcNAc) is a ubiquitous post-translational modification of proteins in eukaryotic cells. 28510447 3 90 theme human 509:513 arg1 diabetes 554:561 diabetes 554:561 diabetes 554:561 Aberrant O-GlcNAc proteins are correlated with many major human diseases, such as Alzheimer's disease, diabetes, and cancer. 28510447 3 90 theme human 509:513 arg1 diseases 515:522 many major human diseases 498:522 many major human diseases 498:522 Aberrant O-GlcNAc proteins are correlated with many major human diseases, such as Alzheimer's disease, diabetes, and cancer. 28510447 3 90 theme human 509:513 arg1 cancer 568:573 cancer 568:573 cancer 568:573 Aberrant O-GlcNAc proteins are correlated with many major human diseases, such as Alzheimer's disease, diabetes, and cancer. 28510447 3 90 theme human 509:513 arg1 disease 545:551 Alzheimer's disease 533:551 Alzheimer's disease 533:551 Aberrant O-GlcNAc proteins are correlated with many major human diseases, such as Alzheimer's disease, diabetes, and cancer. 28510447 5 91 theme immobilized 850:860 arg1 tool 903:906 a convenient tool 890:906 a convenient tool for efficient enrichment of azide-labeled O-GlcNAc proteins from complex biological samples 890:998 In this work, we designed and synthesized a novel thermosensitive immobilized triarylphosphine reagent as a convenient tool for efficient enrichment of azide-labeled O-GlcNAc proteins from complex biological samples. 28510447 5 91 theme immobilized 850:860 arg1 reagent 879:885 a novel thermosensitive immobilized triarylphosphine reagent 826:885 a novel thermosensitive immobilized triarylphosphine reagent 826:885 In this work, we designed and synthesized a novel thermosensitive immobilized triarylphosphine reagent as a convenient tool for efficient enrichment of azide-labeled O-GlcNAc proteins from complex biological samples. 28510447 3 92 theme Aberrant 451:458 arg1 proteins 469:476 Aberrant O-GlcNAc proteins 451:476 Aberrant O-GlcNAc proteins 451:476 Aberrant O-GlcNAc proteins are correlated with many major human diseases, such as Alzheimer's disease, diabetes, and cancer. 28510447 1 93 theme proteins 271:278 arg1 β-N-acetylglucosamine 187:207 O-linked β-N-acetylglucosamine 178:207 O-linked β-N-acetylglucosamine (O-GlcNAc) 178:218 O-linked β-N-acetylglucosamine (O-GlcNAc) is a ubiquitous post-translational modification of proteins in eukaryotic cells. 28510447 1 93 theme proteins 271:278 arg1 modification 255:266 a ubiquitous post-translational modification 223:266 a ubiquitous post-translational modification of proteins in eukaryotic cells 223:298 O-linked β-N-acetylglucosamine (O-GlcNAc) is a ubiquitous post-translational modification of proteins in eukaryotic cells. 28510447 7 94 theme homogeneous 1408:1418 arg1 reaction 1420:1427 homogeneous reaction 1408:1427 homogeneous reaction 1408:1427 As a result, facilitated coupling is achieved between triarylphosphine and azide-labeled O-GlcNAc proteins via Staudinger ligation, due to the increased triarylphosphine concentration, reduced interfacial mass transfer resistance, and steric hindrance in homogeneous reaction. 28510447 3 95 theme many 498:501 arg1 diabetes 554:561 diabetes 554:561 diabetes 554:561 Aberrant O-GlcNAc proteins are correlated with many major human diseases, such as Alzheimer's disease, diabetes, and cancer. 28510447 3 95 theme many 498:501 arg1 diseases 515:522 many major human diseases 498:522 many major human diseases 498:522 Aberrant O-GlcNAc proteins are correlated with many major human diseases, such as Alzheimer's disease, diabetes, and cancer. 28510447 3 95 theme many 498:501 arg1 cancer 568:573 cancer 568:573 cancer 568:573 Aberrant O-GlcNAc proteins are correlated with many major human diseases, such as Alzheimer's disease, diabetes, and cancer. 28510447 3 95 theme many 498:501 arg1 disease 545:551 Alzheimer's disease 533:551 Alzheimer's disease 533:551 Aberrant O-GlcNAc proteins are correlated with many major human diseases, such as Alzheimer's disease, diabetes, and cancer. 28510447 10 96 theme novel 1748:1752 arg1 reagent 1783:1789 This novel immobilized triarylphosphine reagent 1743:1789 This novel immobilized triarylphosphine reagent 1743:1789 This novel immobilized triarylphosphine reagent enables efficient enrichment and sensitive detection of more than 1700 potential O-GlcNAc proteins from HeLa cell using mass spectrometry, demonstrating its potential as a general strategy for low-abundance target enrichment. 28510447 2 97 theme signal 414:419 arg1 transduction 421:432 signal transduction 414:432 signal transduction 414:432 Despite their low abundance, O-GlcNAc-modified proteins play many important roles in regulating gene expression, signal transduction, and cell cycle. 28510447 1 98 theme eukaryotic 283:292 arg1 cells 294:298 eukaryotic cells 283:298 eukaryotic cells 283:298 O-linked β-N-acetylglucosamine (O-GlcNAc) is a ubiquitous post-translational modification of proteins in eukaryotic cells. 27341820 1 0 contain have 115:118 arg1 Glycoconjugates 99:113 Glycoconjugates 99:113 Glycoconjugates 99:113 Glycoconjugates have various functions in differentiation, development, aging and in all aspects of normal functioning of organisms. 27341820 1 0 contain have 115:118 arg2 functions 128:136 various functions 120:136 various functions 120:136 Glycoconjugates have various functions in differentiation, development, aging and in all aspects of normal functioning of organisms. 27341820 6 1 theme oldest 1187:1192 arg1 prepupa 1174:1180 motionless prepupa 1163:1180 motionless prepupa (the oldest sample) 1163:1200 Developmental stages were selected as 3rd (the youngest sample), 5th (young) larval instar, motionless prepupa (the oldest sample), and pupa (adult development). 27341820 6 1 theme oldest 1187:1192 arg1 sample 1194:1199 the oldest sample 1183:1199 the oldest sample 1183:1199 Developmental stages were selected as 3rd (the youngest sample), 5th (young) larval instar, motionless prepupa (the oldest sample), and pupa (adult development). 27341820 3 2 from roles 484:488 arg1 system 505:510 the nervous system 493:510 the nervous system 493:510 Considering their roles in the nervous system, information about their existence in the insect nervous system is rather sparse. 27341820 11 3 theme pupa 1766:1769 arg1 stage 1771:1775 the pupa stage 1762:1775 the pupa stage 1762:1775 It was observed that amounts of monosaccharides increased again in the pupa stage. 27341820 12 4 theme glycoprotein 1894:1905 arg1 differences 1918:1928 some specific glycoprotein expression differences 1880:1928 some specific glycoprotein expression differences between stages 1880:1943 According to lectin blotting, N- and O-linked glycoproteins expressions were different and there were some specific glycoprotein expression differences between stages. 27341820 4 5 theme fucose 841:846 arg1 changes 739:745 the concentration changes 721:745 the concentration changes of glucose, mannose, galactose, N-acetylglucosamine (GlcNAc), N-acetylgalactosamine (GalNAc), fucose, xylose, arabinose, and ribose monosaccharides in the nervous system of Bombyx mori 721:930 Therefore, in order to detect monosaccharide content of N- and O-glycans, we carried out capLC-ESI-MS/MS analysis to determine the concentration changes of glucose, mannose, galactose, N-acetylglucosamine (GlcNAc), N-acetylgalactosamine (GalNAc), fucose, xylose, arabinose, and ribose monosaccharides in the nervous system of Bombyx mori during development and aging processes. 27341820 6 6 theme youngest 1118:1125 arg1 sample 1127:1132 the youngest sample 1114:1132 the youngest sample 1114:1132 Developmental stages were selected as 3rd (the youngest sample), 5th (young) larval instar, motionless prepupa (the oldest sample), and pupa (adult development). 27341820 6 6 theme youngest 1118:1125 arg1 3rd 1109:1111 3rd 1109:1111 3rd (the youngest sample) 1109:1133 Developmental stages were selected as 3rd (the youngest sample), 5th (young) larval instar, motionless prepupa (the oldest sample), and pupa (adult development). 27341820 12 7 link O-linked 1815:1822 arg1 glycoproteins 1824:1836 O-linked glycoproteins 1815:1836 O-linked glycoproteins 1815:1836 According to lectin blotting, N- and O-linked glycoproteins expressions were different and there were some specific glycoprotein expression differences between stages. 27341820 10 8 from stage 1612:1616 arg1 present 1572:1578 present 1572:1578 present 1572:1578 Although all monosaccharides were present most abundantly in the youngest stage (3rd instar), they are generally reduced gradually during the aging process. 27341820 4 9 theme monosaccharide 624:637 arg1 content 639:645 monosaccharide content 624:645 monosaccharide content of N- and O-glycans 624:665 Therefore, in order to detect monosaccharide content of N- and O-glycans, we carried out capLC-ESI-MS/MS analysis to determine the concentration changes of glucose, mannose, galactose, N-acetylglucosamine (GlcNAc), N-acetylgalactosamine (GalNAc), fucose, xylose, arabinose, and ribose monosaccharides in the nervous system of Bombyx mori during development and aging processes. 27341820 6 10 theme motionless 1163:1172 arg1 stages 1085:1090 Developmental stages 1071:1090 Developmental stages 1071:1090 Developmental stages were selected as 3rd (the youngest sample), 5th (young) larval instar, motionless prepupa (the oldest sample), and pupa (adult development). 27341820 6 10 theme motionless 1163:1172 arg1 prepupa 1174:1180 motionless prepupa 1163:1180 motionless prepupa (the oldest sample) 1163:1200 Developmental stages were selected as 3rd (the youngest sample), 5th (young) larval instar, motionless prepupa (the oldest sample), and pupa (adult development). 27341820 6 10 theme motionless 1163:1172 arg1 sample 1194:1199 the oldest sample 1183:1199 the oldest sample 1183:1199 Developmental stages were selected as 3rd (the youngest sample), 5th (young) larval instar, motionless prepupa (the oldest sample), and pupa (adult development). 27341820 12 11 gly glycoproteins 1824:1836 arg1 glycoproteins 1824:1836 O-linked glycoproteins 1815:1836 O-linked glycoproteins 1815:1836 According to lectin blotting, N- and O-linked glycoproteins expressions were different and there were some specific glycoprotein expression differences between stages. 27341820 7 12 theme PMP 1300:1302 arg1 agent 1304:1308 PMP agent 1300:1308 PMP agent 1300:1308 Derivatization of monosaccharides was performed with a solution of PMP agent and analyzed with capLC-ESI-MS/MS. 27341820 4 13 theme monosaccharides 879:893 arg1 changes 739:745 the concentration changes 721:745 the concentration changes of glucose, mannose, galactose, N-acetylglucosamine (GlcNAc), N-acetylgalactosamine (GalNAc), fucose, xylose, arabinose, and ribose monosaccharides in the nervous system of Bombyx mori 721:930 Therefore, in order to detect monosaccharide content of N- and O-glycans, we carried out capLC-ESI-MS/MS analysis to determine the concentration changes of glucose, mannose, galactose, N-acetylglucosamine (GlcNAc), N-acetylgalactosamine (GalNAc), fucose, xylose, arabinose, and ribose monosaccharides in the nervous system of Bombyx mori during development and aging processes. 27341820 6 14 theme larval 1148:1153 arg1 instar 1155:1160 5th (young) larval instar 1136:1160 5th (young) larval instar 1136:1160 Developmental stages were selected as 3rd (the youngest sample), 5th (young) larval instar, motionless prepupa (the oldest sample), and pupa (adult development). 27341820 6 14 theme larval 1148:1153 arg1 stages 1085:1090 Developmental stages 1071:1090 Developmental stages 1071:1090 Developmental stages were selected as 3rd (the youngest sample), 5th (young) larval instar, motionless prepupa (the oldest sample), and pupa (adult development). 27341820 1 15 theme normal 199:204 arg1 aspects 188:194 all aspects 184:194 all aspects of normal functioning of organisms 184:229 Glycoconjugates have various functions in differentiation, development, aging and in all aspects of normal functioning of organisms. 27341820 4 16 theme xylose 849:854 arg1 changes 739:745 the concentration changes 721:745 the concentration changes of glucose, mannose, galactose, N-acetylglucosamine (GlcNAc), N-acetylgalactosamine (GalNAc), fucose, xylose, arabinose, and ribose monosaccharides in the nervous system of Bombyx mori 721:930 Therefore, in order to detect monosaccharide content of N- and O-glycans, we carried out capLC-ESI-MS/MS analysis to determine the concentration changes of glucose, mannose, galactose, N-acetylglucosamine (GlcNAc), N-acetylgalactosamine (GalNAc), fucose, xylose, arabinose, and ribose monosaccharides in the nervous system of Bombyx mori during development and aging processes. 27341820 8 17 theme lectin 1349:1354 arg1 blotting 1356:1363 lectin blotting 1349:1363 lectin blotting 1349:1363 For lectin blotting, determination of glycan types was carried out with Galanthus nivalis agglutinin and Peanut agglutinin lectins. 27341820 6 18 theme young 1141:1145 arg1 instar 1155:1160 5th (young) larval instar 1136:1160 5th (young) larval instar 1136:1160 Developmental stages were selected as 3rd (the youngest sample), 5th (young) larval instar, motionless prepupa (the oldest sample), and pupa (adult development). 27341820 6 18 theme young 1141:1145 arg1 stages 1085:1090 Developmental stages 1071:1090 Developmental stages 1071:1090 Developmental stages were selected as 3rd (the youngest sample), 5th (young) larval instar, motionless prepupa (the oldest sample), and pupa (adult development). 27341820 13 19 from state 1992:1996 arg1 system 2025:2030 the nervous system 2013:2030 the nervous system 2013:2030 These findings suggest that the glycosylation state of proteins in the nervous system changes during development and aging in insects in a similar fashion to that reported for vertebrates. 27341820 3 20 theme nervous 561:567 arg1 system 569:574 the insect nervous system 550:574 the insect nervous system 550:574 Considering their roles in the nervous system, information about their existence in the insect nervous system is rather sparse. 27341820 4 21 theme arabinose 857:865 arg1 changes 739:745 the concentration changes 721:745 the concentration changes of glucose, mannose, galactose, N-acetylglucosamine (GlcNAc), N-acetylgalactosamine (GalNAc), fucose, xylose, arabinose, and ribose monosaccharides in the nervous system of Bombyx mori 721:930 Therefore, in order to detect monosaccharide content of N- and O-glycans, we carried out capLC-ESI-MS/MS analysis to determine the concentration changes of glucose, mannose, galactose, N-acetylglucosamine (GlcNAc), N-acetylgalactosamine (GalNAc), fucose, xylose, arabinose, and ribose monosaccharides in the nervous system of Bombyx mori during development and aging processes. 27341820 6 22 theme 5th 1136:1138 arg1 instar 1155:1160 5th (young) larval instar 1136:1160 5th (young) larval instar 1136:1160 Developmental stages were selected as 3rd (the youngest sample), 5th (young) larval instar, motionless prepupa (the oldest sample), and pupa (adult development). 27341820 6 22 theme 5th 1136:1138 arg1 stages 1085:1090 Developmental stages 1071:1090 Developmental stages 1071:1090 Developmental stages were selected as 3rd (the youngest sample), 5th (young) larval instar, motionless prepupa (the oldest sample), and pupa (adult development). 27341820 4 23 theme capLC-ESI-MS/MS 683:697 arg1 analysis 699:706 capLC-ESI-MS/MS analysis 683:706 capLC-ESI-MS/MS analysis 683:706 Therefore, in order to detect monosaccharide content of N- and O-glycans, we carried out capLC-ESI-MS/MS analysis to determine the concentration changes of glucose, mannose, galactose, N-acetylglucosamine (GlcNAc), N-acetylgalactosamine (GalNAc), fucose, xylose, arabinose, and ribose monosaccharides in the nervous system of Bombyx mori during development and aging processes. 27341820 5 24 theme lectin 994:999 arg1 blotting 1001:1008 lectin blotting 994:1008 lectin blotting 994:1008 In addition to LC-MS, lectin blotting was done to detect quantitative changes in N- and O-glycans. 27341820 4 25 theme Bombyx 920:925 arg1 mori 927:930 Bombyx mori 920:930 Bombyx mori 920:930 Therefore, in order to detect monosaccharide content of N- and O-glycans, we carried out capLC-ESI-MS/MS analysis to determine the concentration changes of glucose, mannose, galactose, N-acetylglucosamine (GlcNAc), N-acetylgalactosamine (GalNAc), fucose, xylose, arabinose, and ribose monosaccharides in the nervous system of Bombyx mori during development and aging processes. 27341820 13 26 theme glycosylation 1978:1990 arg1 state 1992:1996 the glycosylation state 1974:1996 the glycosylation state of proteins in the nervous system 1974:2030 These findings suggest that the glycosylation state of proteins in the nervous system changes during development and aging in insects in a similar fashion to that reported for vertebrates. 27341820 8 27 theme types 1390:1394 arg1 determination 1366:1378 determination 1366:1378 determination of glycan types 1366:1394 For lectin blotting, determination of glycan types was carried out with Galanthus nivalis agglutinin and Peanut agglutinin lectins. 27341820 0 28 theme system 62:67 arg1 profiling 15:23 Monosaccharide profiling 0:23 Monosaccharide profiling of silkworm (Bombyx mori L.) nervous system during development and aging 0:96 Monosaccharide profiling of silkworm (Bombyx mori L.) nervous system during development and aging. 27341820 13 29 theme nervous 2017:2023 arg1 system 2025:2030 the nervous system 2013:2030 the nervous system 2013:2030 These findings suggest that the glycosylation state of proteins in the nervous system changes during development and aging in insects in a similar fashion to that reported for vertebrates. 27341820 10 30 attach present 1572:1578 arg1 stage 1612:1616 the youngest stage 1599:1616 the youngest stage (3rd instar) 1599:1629 Although all monosaccharides were present most abundantly in the youngest stage (3rd instar), they are generally reduced gradually during the aging process. 27341820 10 30 attach present 1572:1578 arg1 instar 1623:1628 3rd instar 1619:1628 3rd instar 1619:1628 Although all monosaccharides were present most abundantly in the youngest stage (3rd instar), they are generally reduced gradually during the aging process. 27341820 10 30 attach present 1572:1578 arg2 monosaccharides 1551:1565 all monosaccharides 1547:1565 all monosaccharides 1547:1565 Although all monosaccharides were present most abundantly in the youngest stage (3rd instar), they are generally reduced gradually during the aging process. 27341820 5 31 theme quantitative 1029:1040 arg1 changes 1042:1048 quantitative changes 1029:1048 quantitative changes in N- and O-glycans 1029:1068 In addition to LC-MS, lectin blotting was done to detect quantitative changes in N- and O-glycans. 27341820 4 32 from changes 739:745 arg1 system 910:915 the nervous system 898:915 the nervous system of Bombyx mori 898:930 Therefore, in order to detect monosaccharide content of N- and O-glycans, we carried out capLC-ESI-MS/MS analysis to determine the concentration changes of glucose, mannose, galactose, N-acetylglucosamine (GlcNAc), N-acetylgalactosamine (GalNAc), fucose, xylose, arabinose, and ribose monosaccharides in the nervous system of Bombyx mori during development and aging processes. 27341820 9 33 from glucose 1529:1535 arg1 stages 1484:1489 all stages 1480:1489 all stages 1480:1489 In all stages, the most abundant monosaccharide was glucose. 27341820 4 34 theme glucose 750:756 arg1 changes 739:745 the concentration changes 721:745 the concentration changes of glucose, mannose, galactose, N-acetylglucosamine (GlcNAc), N-acetylgalactosamine (GalNAc), fucose, xylose, arabinose, and ribose monosaccharides in the nervous system of Bombyx mori 721:930 Therefore, in order to detect monosaccharide content of N- and O-glycans, we carried out capLC-ESI-MS/MS analysis to determine the concentration changes of glucose, mannose, galactose, N-acetylglucosamine (GlcNAc), N-acetylgalactosamine (GalNAc), fucose, xylose, arabinose, and ribose monosaccharides in the nervous system of Bombyx mori during development and aging processes. 27341820 8 35 theme nivalis 1427:1433 arg1 agglutinin 1435:1444 Galanthus nivalis agglutinin 1417:1444 Galanthus nivalis agglutinin 1417:1444 For lectin blotting, determination of glycan types was carried out with Galanthus nivalis agglutinin and Peanut agglutinin lectins. 27341820 0 36 theme Monosaccharide 0:13 arg1 profiling 15:23 Monosaccharide profiling 0:23 Monosaccharide profiling of silkworm (Bombyx mori L.) nervous system during development and aging 0:96 Monosaccharide profiling of silkworm (Bombyx mori L.) nervous system during development and aging. 27341820 12 37 theme lectin 1791:1796 arg1 blotting 1798:1805 lectin blotting 1791:1805 lectin blotting 1791:1805 According to lectin blotting, N- and O-linked glycoproteins expressions were different and there were some specific glycoprotein expression differences between stages. 27341820 2 38 theme brain 404:408 arg1 development 410:420 brain development 404:420 brain development 404:420 The reason for increased research on this topic is that glycoconjugates locate mostly on the cell surface and play crucial biological roles in the nervous system including brain development, synaptic plasticity, learning, and memory. 27341820 5 39 from changes 1042:1048 arg1 O-glycans 1060:1068 O-glycans 1060:1068 O-glycans 1060:1068 In addition to LC-MS, lectin blotting was done to detect quantitative changes in N- and O-glycans. 27341820 5 39 from changes 1042:1048 arg1 N- 1053:1054 N- 1053:1054 N- 1053:1054 In addition to LC-MS, lectin blotting was done to detect quantitative changes in N- and O-glycans. 27341820 8 40 theme agglutinin 1457:1466 arg1 lectins 1468:1474 Galanthus nivalis agglutinin and Peanut agglutinin lectins 1417:1474 Galanthus nivalis agglutinin and Peanut agglutinin lectins 1417:1474 For lectin blotting, determination of glycan types was carried out with Galanthus nivalis agglutinin and Peanut agglutinin lectins. 27341820 13 41 from aging 2063:2067 arg1 insects 2072:2078 insects 2072:2078 insects 2072:2078 These findings suggest that the glycosylation state of proteins in the nervous system changes during development and aging in insects in a similar fashion to that reported for vertebrates. 27341820 4 42 theme N-acetylglucosamine 779:797 arg1 changes 739:745 the concentration changes 721:745 the concentration changes of glucose, mannose, galactose, N-acetylglucosamine (GlcNAc), N-acetylgalactosamine (GalNAc), fucose, xylose, arabinose, and ribose monosaccharides in the nervous system of Bombyx mori 721:930 Therefore, in order to detect monosaccharide content of N- and O-glycans, we carried out capLC-ESI-MS/MS analysis to determine the concentration changes of glucose, mannose, galactose, N-acetylglucosamine (GlcNAc), N-acetylgalactosamine (GalNAc), fucose, xylose, arabinose, and ribose monosaccharides in the nervous system of Bombyx mori during development and aging processes. 27341820 4 43 dep order 608:612 arg1 detect 617:622 detect 617:622 to detect monosaccharide content of N- and O-glycans 614:665 Therefore, in order to detect monosaccharide content of N- and O-glycans, we carried out capLC-ESI-MS/MS analysis to determine the concentration changes of glucose, mannose, galactose, N-acetylglucosamine (GlcNAc), N-acetylgalactosamine (GalNAc), fucose, xylose, arabinose, and ribose monosaccharides in the nervous system of Bombyx mori during development and aging processes. 27341820 2 44 theme cell 325:328 arg1 surface 330:336 the cell surface 321:336 the cell surface 321:336 The reason for increased research on this topic is that glycoconjugates locate mostly on the cell surface and play crucial biological roles in the nervous system including brain development, synaptic plasticity, learning, and memory. 27341820 9 45 theme abundant 1501:1508 arg1 glucose 1529:1535 glucose 1529:1535 glucose 1529:1535 In all stages, the most abundant monosaccharide was glucose. 27341820 9 45 theme abundant 1501:1508 arg1 monosaccharide 1510:1523 the most abundant monosaccharide 1492:1523 the most abundant monosaccharide 1492:1523 In all stages, the most abundant monosaccharide was glucose. 27341820 4 46 theme mannose 759:765 arg1 changes 739:745 the concentration changes 721:745 the concentration changes of glucose, mannose, galactose, N-acetylglucosamine (GlcNAc), N-acetylgalactosamine (GalNAc), fucose, xylose, arabinose, and ribose monosaccharides in the nervous system of Bombyx mori 721:930 Therefore, in order to detect monosaccharide content of N- and O-glycans, we carried out capLC-ESI-MS/MS analysis to determine the concentration changes of glucose, mannose, galactose, N-acetylglucosamine (GlcNAc), N-acetylgalactosamine (GalNAc), fucose, xylose, arabinose, and ribose monosaccharides in the nervous system of Bombyx mori during development and aging processes. 27341820 11 47 theme monosaccharides 1727:1741 arg1 monosaccharides 1727:1741 monosaccharides 1727:1741 monosaccharides 1727:1741 It was observed that amounts of monosaccharides increased again in the pupa stage. 27341820 11 47 theme monosaccharides 1727:1741 arg1 amounts 1716:1722 amounts 1716:1722 amounts of monosaccharides 1716:1741 It was observed that amounts of monosaccharides increased again in the pupa stage. 27341820 4 48 theme galactose 768:776 arg1 changes 739:745 the concentration changes 721:745 the concentration changes of glucose, mannose, galactose, N-acetylglucosamine (GlcNAc), N-acetylgalactosamine (GalNAc), fucose, xylose, arabinose, and ribose monosaccharides in the nervous system of Bombyx mori 721:930 Therefore, in order to detect monosaccharide content of N- and O-glycans, we carried out capLC-ESI-MS/MS analysis to determine the concentration changes of glucose, mannose, galactose, N-acetylglucosamine (GlcNAc), N-acetylgalactosamine (GalNAc), fucose, xylose, arabinose, and ribose monosaccharides in the nervous system of Bombyx mori during development and aging processes. 27341820 12 49 gly glycoprotein 1894:1905 arg1 glycoprotein 1894:1905 some specific glycoprotein expression differences 1880:1928 some specific glycoprotein expression differences between stages 1880:1943 According to lectin blotting, N- and O-linked glycoproteins expressions were different and there were some specific glycoprotein expression differences between stages. 27341820 2 50 theme crucial 347:353 arg1 roles 366:370 crucial biological roles 347:370 crucial biological roles 347:370 The reason for increased research on this topic is that glycoconjugates locate mostly on the cell surface and play crucial biological roles in the nervous system including brain development, synaptic plasticity, learning, and memory. 27341820 1 51 theme organisms 221:229 arg1 normal 199:204 normal 199:204 normal 199:204 Glycoconjugates have various functions in differentiation, development, aging and in all aspects of normal functioning of organisms. 27341820 13 52 from development 2047:2057 arg1 insects 2072:2078 insects 2072:2078 insects 2072:2078 These findings suggest that the glycosylation state of proteins in the nervous system changes during development and aging in insects in a similar fashion to that reported for vertebrates. 27341820 10 53 located present 1572:1578 arg1 stage 1612:1616 the youngest stage 1599:1616 the youngest stage (3rd instar) 1599:1629 Although all monosaccharides were present most abundantly in the youngest stage (3rd instar), they are generally reduced gradually during the aging process. 27341820 10 53 located present 1572:1578 arg1 instar 1623:1628 3rd instar 1619:1628 3rd instar 1619:1628 Although all monosaccharides were present most abundantly in the youngest stage (3rd instar), they are generally reduced gradually during the aging process. 27341820 10 53 located present 1572:1578 arg2 monosaccharides 1551:1565 all monosaccharides 1547:1565 all monosaccharides 1547:1565 Although all monosaccharides were present most abundantly in the youngest stage (3rd instar), they are generally reduced gradually during the aging process. 27341820 12 54 theme specific 1885:1892 arg1 differences 1918:1928 some specific glycoprotein expression differences 1880:1928 some specific glycoprotein expression differences between stages 1880:1943 According to lectin blotting, N- and O-linked glycoproteins expressions were different and there were some specific glycoprotein expression differences between stages. 27341820 12 55 theme expression 1907:1916 arg1 differences 1918:1928 some specific glycoprotein expression differences 1880:1928 some specific glycoprotein expression differences between stages 1880:1943 According to lectin blotting, N- and O-linked glycoproteins expressions were different and there were some specific glycoprotein expression differences between stages. 27341820 4 56 contain carried 671:677 arg2 analysis 699:706 capLC-ESI-MS/MS analysis 683:706 capLC-ESI-MS/MS analysis 683:706 Therefore, in order to detect monosaccharide content of N- and O-glycans, we carried out capLC-ESI-MS/MS analysis to determine the concentration changes of glucose, mannose, galactose, N-acetylglucosamine (GlcNAc), N-acetylgalactosamine (GalNAc), fucose, xylose, arabinose, and ribose monosaccharides in the nervous system of Bombyx mori during development and aging processes. 27341820 4 56 contain carried 671:677 arg3 order 608:612 order 608:612 order to detect monosaccharide content of N- and O-glycans 608:665 Therefore, in order to detect monosaccharide content of N- and O-glycans, we carried out capLC-ESI-MS/MS analysis to determine the concentration changes of glucose, mannose, galactose, N-acetylglucosamine (GlcNAc), N-acetylgalactosamine (GalNAc), fucose, xylose, arabinose, and ribose monosaccharides in the nervous system of Bombyx mori during development and aging processes. 27341820 4 56 contain carried 671:677 arg1 we 668:669 we 668:669 we 668:669 Therefore, in order to detect monosaccharide content of N- and O-glycans, we carried out capLC-ESI-MS/MS analysis to determine the concentration changes of glucose, mannose, galactose, N-acetylglucosamine (GlcNAc), N-acetylgalactosamine (GalNAc), fucose, xylose, arabinose, and ribose monosaccharides in the nervous system of Bombyx mori during development and aging processes. 27341820 10 57 theme aging 1680:1684 arg1 process 1686:1692 the aging process 1676:1692 the aging process 1676:1692 Although all monosaccharides were present most abundantly in the youngest stage (3rd instar), they are generally reduced gradually during the aging process. 27341820 4 58 theme N-acetylgalactosamine 809:829 arg1 changes 739:745 the concentration changes 721:745 the concentration changes of glucose, mannose, galactose, N-acetylglucosamine (GlcNAc), N-acetylgalactosamine (GalNAc), fucose, xylose, arabinose, and ribose monosaccharides in the nervous system of Bombyx mori 721:930 Therefore, in order to detect monosaccharide content of N- and O-glycans, we carried out capLC-ESI-MS/MS analysis to determine the concentration changes of glucose, mannose, galactose, N-acetylglucosamine (GlcNAc), N-acetylgalactosamine (GalNAc), fucose, xylose, arabinose, and ribose monosaccharides in the nervous system of Bombyx mori during development and aging processes. 27341820 7 59 theme agent 1304:1308 arg1 solution 1288:1295 a solution 1286:1295 a solution of PMP agent 1286:1308 Derivatization of monosaccharides was performed with a solution of PMP agent and analyzed with capLC-ESI-MS/MS. 27341820 6 60 theme adult 1213:1217 arg1 pupa 1207:1210 pupa 1207:1210 pupa (adult development) 1207:1230 Developmental stages were selected as 3rd (the youngest sample), 5th (young) larval instar, motionless prepupa (the oldest sample), and pupa (adult development). 27341820 6 60 theme adult 1213:1217 arg1 development 1219:1229 adult development 1213:1229 adult development 1213:1229 Developmental stages were selected as 3rd (the youngest sample), 5th (young) larval instar, motionless prepupa (the oldest sample), and pupa (adult development). 27341820 4 61 theme ribose 872:877 arg1 monosaccharides 879:893 ribose monosaccharides 872:893 ribose monosaccharides 872:893 Therefore, in order to detect monosaccharide content of N- and O-glycans, we carried out capLC-ESI-MS/MS analysis to determine the concentration changes of glucose, mannose, galactose, N-acetylglucosamine (GlcNAc), N-acetylgalactosamine (GalNAc), fucose, xylose, arabinose, and ribose monosaccharides in the nervous system of Bombyx mori during development and aging processes. 27341820 12 62 dep N- 1808:1809 arg1 expressions 1838:1848 expressions 1838:1848 expressions 1838:1848 According to lectin blotting, N- and O-linked glycoproteins expressions were different and there were some specific glycoprotein expression differences between stages. 27341820 3 63 theme insect 554:559 arg1 system 569:574 the insect nervous system 550:574 the insect nervous system 550:574 Considering their roles in the nervous system, information about their existence in the insect nervous system is rather sparse. 27341820 13 64 gly glycosylation 1978:1990 arg1 proteins 2001:2008 proteins 2001:2008 proteins 2001:2008 These findings suggest that the glycosylation state of proteins in the nervous system changes during development and aging in insects in a similar fashion to that reported for vertebrates. 27341820 2 65 theme increased 247:255 arg1 research 257:264 increased research 247:264 increased research on this topic 247:278 The reason for increased research on this topic is that glycoconjugates locate mostly on the cell surface and play crucial biological roles in the nervous system including brain development, synaptic plasticity, learning, and memory. 27341820 1 66 theme various 120:126 arg1 functions 128:136 various functions 120:136 various functions 120:136 Glycoconjugates have various functions in differentiation, development, aging and in all aspects of normal functioning of organisms. 27341820 2 67 from research 257:264 arg1 topic 274:278 this topic 269:278 this topic 269:278 The reason for increased research on this topic is that glycoconjugates locate mostly on the cell surface and play crucial biological roles in the nervous system including brain development, synaptic plasticity, learning, and memory. 27341820 8 68 theme glycan 1383:1388 arg1 types 1390:1394 glycan types 1383:1394 glycan types 1383:1394 For lectin blotting, determination of glycan types was carried out with Galanthus nivalis agglutinin and Peanut agglutinin lectins. 27341820 7 69 theme monosaccharides 1251:1265 arg1 Derivatization 1233:1246 Derivatization 1233:1246 Derivatization of monosaccharides 1233:1265 Derivatization of monosaccharides was performed with a solution of PMP agent and analyzed with capLC-ESI-MS/MS. 27341820 10 70 theme youngest 1603:1610 arg1 stage 1612:1616 the youngest stage 1599:1616 the youngest stage (3rd instar) 1599:1629 Although all monosaccharides were present most abundantly in the youngest stage (3rd instar), they are generally reduced gradually during the aging process. 27341820 10 70 theme youngest 1603:1610 arg1 instar 1623:1628 3rd instar 1619:1628 3rd instar 1619:1628 Although all monosaccharides were present most abundantly in the youngest stage (3rd instar), they are generally reduced gradually during the aging process. 27341820 0 71 theme nervous 54:60 arg1 system 62:67 silkworm (Bombyx mori L.) nervous system 28:67 silkworm (Bombyx mori L.) nervous system 28:67 Monosaccharide profiling of silkworm (Bombyx mori L.) nervous system during development and aging. 27341820 0 71 theme nervous 54:60 arg1 Bombyx 38:43 Bombyx 38:43 Bombyx 38:43 Monosaccharide profiling of silkworm (Bombyx mori L.) nervous system during development and aging. 27341820 4 72 theme N- 650:651 arg1 content 639:645 monosaccharide content 624:645 monosaccharide content of N- and O-glycans 624:665 Therefore, in order to detect monosaccharide content of N- and O-glycans, we carried out capLC-ESI-MS/MS analysis to determine the concentration changes of glucose, mannose, galactose, N-acetylglucosamine (GlcNAc), N-acetylgalactosamine (GalNAc), fucose, xylose, arabinose, and ribose monosaccharides in the nervous system of Bombyx mori during development and aging processes. 27341820 4 73 theme mori 927:930 arg1 system 910:915 the nervous system 898:915 the nervous system of Bombyx mori 898:930 Therefore, in order to detect monosaccharide content of N- and O-glycans, we carried out capLC-ESI-MS/MS analysis to determine the concentration changes of glucose, mannose, galactose, N-acetylglucosamine (GlcNAc), N-acetylgalactosamine (GalNAc), fucose, xylose, arabinose, and ribose monosaccharides in the nervous system of Bombyx mori during development and aging processes. 27341820 4 74 theme O-glycans 657:665 arg1 content 639:645 monosaccharide content 624:645 monosaccharide content of N- and O-glycans 624:665 Therefore, in order to detect monosaccharide content of N- and O-glycans, we carried out capLC-ESI-MS/MS analysis to determine the concentration changes of glucose, mannose, galactose, N-acetylglucosamine (GlcNAc), N-acetylgalactosamine (GalNAc), fucose, xylose, arabinose, and ribose monosaccharides in the nervous system of Bombyx mori during development and aging processes. 27341820 3 75 from information 513:523 arg1 system 569:574 the insect nervous system 550:574 the insect nervous system 550:574 Considering their roles in the nervous system, information about their existence in the insect nervous system is rather sparse. 27341820 13 76 theme proteins 2001:2008 arg1 state 1992:1996 the glycosylation state 1974:1996 the glycosylation state of proteins in the nervous system 1974:2030 These findings suggest that the glycosylation state of proteins in the nervous system changes during development and aging in insects in a similar fashion to that reported for vertebrates. 27341820 12 77 theme O-linked 1815:1822 arg1 glycoproteins 1824:1836 O-linked glycoproteins 1815:1836 O-linked glycoproteins 1815:1836 According to lectin blotting, N- and O-linked glycoproteins expressions were different and there were some specific glycoprotein expression differences between stages. 27341820 8 78 theme Galanthus 1417:1425 arg1 agglutinin 1435:1444 Galanthus nivalis agglutinin 1417:1444 Galanthus nivalis agglutinin 1417:1444 For lectin blotting, determination of glycan types was carried out with Galanthus nivalis agglutinin and Peanut agglutinin lectins. 27341820 4 79 theme concentration 725:737 arg1 changes 739:745 the concentration changes 721:745 the concentration changes of glucose, mannose, galactose, N-acetylglucosamine (GlcNAc), N-acetylgalactosamine (GalNAc), fucose, xylose, arabinose, and ribose monosaccharides in the nervous system of Bombyx mori 721:930 Therefore, in order to detect monosaccharide content of N- and O-glycans, we carried out capLC-ESI-MS/MS analysis to determine the concentration changes of glucose, mannose, galactose, N-acetylglucosamine (GlcNAc), N-acetylgalactosamine (GalNAc), fucose, xylose, arabinose, and ribose monosaccharides in the nervous system of Bombyx mori during development and aging processes. 27341820 4 80 theme nervous 902:908 arg1 system 910:915 the nervous system 898:915 the nervous system of Bombyx mori 898:930 Therefore, in order to detect monosaccharide content of N- and O-glycans, we carried out capLC-ESI-MS/MS analysis to determine the concentration changes of glucose, mannose, galactose, N-acetylglucosamine (GlcNAc), N-acetylgalactosamine (GalNAc), fucose, xylose, arabinose, and ribose monosaccharides in the nervous system of Bombyx mori during development and aging processes. 27341820 8 81 theme agglutinin 1435:1444 arg1 lectins 1468:1474 Galanthus nivalis agglutinin and Peanut agglutinin lectins 1417:1474 Galanthus nivalis agglutinin and Peanut agglutinin lectins 1417:1474 For lectin blotting, determination of glycan types was carried out with Galanthus nivalis agglutinin and Peanut agglutinin lectins. 27341820 2 82 theme synaptic 423:430 arg1 plasticity 432:441 synaptic plasticity 423:441 synaptic plasticity 423:441 The reason for increased research on this topic is that glycoconjugates locate mostly on the cell surface and play crucial biological roles in the nervous system including brain development, synaptic plasticity, learning, and memory. 27341820 8 83 theme Peanut 1450:1455 arg1 agglutinin 1457:1466 Peanut agglutinin 1450:1466 Peanut agglutinin 1450:1466 For lectin blotting, determination of glycan types was carried out with Galanthus nivalis agglutinin and Peanut agglutinin lectins. 27341820 2 84 theme biological 355:364 arg1 roles 366:370 crucial biological roles 347:370 crucial biological roles 347:370 The reason for increased research on this topic is that glycoconjugates locate mostly on the cell surface and play crucial biological roles in the nervous system including brain development, synaptic plasticity, learning, and memory. 27341820 0 85 theme silkworm 28:35 arg1 system 62:67 silkworm (Bombyx mori L.) nervous system 28:67 silkworm (Bombyx mori L.) nervous system 28:67 Monosaccharide profiling of silkworm (Bombyx mori L.) nervous system during development and aging. 27341820 0 85 theme silkworm 28:35 arg1 Bombyx 38:43 Bombyx 38:43 Bombyx 38:43 Monosaccharide profiling of silkworm (Bombyx mori L.) nervous system during development and aging. 27341820 2 86 theme nervous 379:385 arg1 system 387:392 the nervous system 375:392 the nervous system including brain development, synaptic plasticity, learning, and memory 375:463 The reason for increased research on this topic is that glycoconjugates locate mostly on the cell surface and play crucial biological roles in the nervous system including brain development, synaptic plasticity, learning, and memory. 27341820 0 87 dep Bombyx 38:43 arg1 L. 50:51 Bombyx mori L. 38:51 Bombyx mori L. 38:51 Monosaccharide profiling of silkworm (Bombyx mori L.) nervous system during development and aging. 27341820 6 88 theme Developmental 1071:1083 arg1 pupa 1207:1210 pupa 1207:1210 pupa (adult development) 1207:1230 Developmental stages were selected as 3rd (the youngest sample), 5th (young) larval instar, motionless prepupa (the oldest sample), and pupa (adult development). 27341820 6 88 theme Developmental 1071:1083 arg1 stages 1085:1090 Developmental stages 1071:1090 Developmental stages 1071:1090 Developmental stages were selected as 3rd (the youngest sample), 5th (young) larval instar, motionless prepupa (the oldest sample), and pupa (adult development). 27341820 6 88 theme Developmental 1071:1083 arg1 prepupa 1174:1180 motionless prepupa 1163:1180 motionless prepupa (the oldest sample) 1163:1200 Developmental stages were selected as 3rd (the youngest sample), 5th (young) larval instar, motionless prepupa (the oldest sample), and pupa (adult development). 27341820 6 88 theme Developmental 1071:1083 arg1 instar 1155:1160 5th (young) larval instar 1136:1160 5th (young) larval instar 1136:1160 Developmental stages were selected as 3rd (the youngest sample), 5th (young) larval instar, motionless prepupa (the oldest sample), and pupa (adult development). 27341820 6 88 theme Developmental 1071:1083 arg1 3rd 1109:1111 3rd 1109:1111 3rd (the youngest sample) 1109:1133 Developmental stages were selected as 3rd (the youngest sample), 5th (young) larval instar, motionless prepupa (the oldest sample), and pupa (adult development). 27341820 4 89 theme aging 955:959 arg1 processes 961:969 aging processes 955:969 aging processes 955:969 Therefore, in order to detect monosaccharide content of N- and O-glycans, we carried out capLC-ESI-MS/MS analysis to determine the concentration changes of glucose, mannose, galactose, N-acetylglucosamine (GlcNAc), N-acetylgalactosamine (GalNAc), fucose, xylose, arabinose, and ribose monosaccharides in the nervous system of Bombyx mori during development and aging processes. 27341820 13 90 theme similar 2085:2091 arg1 fashion 2093:2099 a similar fashion 2083:2099 a similar fashion to that reported for vertebrates 2083:2132 These findings suggest that the glycosylation state of proteins in the nervous system changes during development and aging in insects in a similar fashion to that reported for vertebrates. 27341820 10 91 from present 1572:1578 arg1 stage 1612:1616 the youngest stage 1599:1616 the youngest stage (3rd instar) 1599:1629 Although all monosaccharides were present most abundantly in the youngest stage (3rd instar), they are generally reduced gradually during the aging process. 27341820 10 91 from present 1572:1578 arg1 instar 1623:1628 3rd instar 1619:1628 3rd instar 1619:1628 Although all monosaccharides were present most abundantly in the youngest stage (3rd instar), they are generally reduced gradually during the aging process. 27341820 3 92 theme nervous 497:503 arg1 system 505:510 the nervous system 493:510 the nervous system 493:510 Considering their roles in the nervous system, information about their existence in the insect nervous system is rather sparse. 29997861 9 0 theme useful 1602:1607 arg1 tools 1609:1613 generally useful tools 1592:1613 generally useful tools for the study of O-GlcNAc 1592:1639 Inhibitors from this series will prove generally useful tools for the study of O-GlcNAc. 29997861 5 1 with complex 881:887 arg1 homologue 902:910 an hOGA homologue 894:910 an hOGA homologue 894:910 Structural data of inhibitors in complex with an hOGA homologue reveals the basis for variation in binding among these compounds. 29997861 3 2 theme carbohydrate-based 555:572 arg1 inhibitors 574:583 tight binding carbohydrate-based inhibitors 541:583 tight binding carbohydrate-based inhibitors of human OGA (hOGA) 541:603 Here we synthesize and study a series of tight binding carbohydrate-based inhibitors of human OGA (hOGA). 29997861 2 3 from proteins 353:360 arg1 O-GlcNAc 339:346 O-GlcNAc 339:346 O-GlcNAc from proteins 339:360 Inhibitors of O-GlcNAc hydrolase (OGA), the enzyme that removes O-GlcNAc from proteins, lead to increased O-GlcNAc levels in cells and are seeing widespread adoption in the field as a research tool used in cells and in vivo. 29997861 6 4 theme protonation 1137:1147 arg1 driver 1181:1186 a key driver 1175:1186 a key driver of binding 1175:1197 Using linear free energy analyses, we show binding of these 2'-aminothiazoline inhibitors depends on the pKa of the aminothiazoline ring system, revealing the protonation state of the inhibitor is a key driver of binding. 29997861 6 4 theme protonation 1137:1147 arg1 state 1149:1153 the protonation state 1133:1153 the protonation state of the inhibitor 1133:1170 Using linear free energy analyses, we show binding of these 2'-aminothiazoline inhibitors depends on the pKa of the aminothiazoline ring system, revealing the protonation state of the inhibitor is a key driver of binding. 29997861 10 5 theme catalytic 1681:1689 arg1 mechanism 1691:1699 the catalytic mechanism 1677:1699 the catalytic mechanism of hOGA 1677:1707 The new insights gained here, into the catalytic mechanism of hOGA and the fundamental drivers of potency and selectivity of OGA inhibitors, should enable tuning of hOGA inhibitors with desirable properties. 29997861 4 6 theme human 814:818 arg1 β-hexosaminidase 830:845 mechanistically related human lysosomal β-hexosaminidase 790:845 mechanistically related human lysosomal β-hexosaminidase 790:845 The most potent of these 2'-aminothiazolines binds with a sub-nanomolar Ki value to hOGA (510 ± 50 pM) and the most selective has greater than 1 800 000-fold selectivity for hOGA over mechanistically related human lysosomal β-hexosaminidase. 29997861 3 7 theme binding 547:553 arg1 inhibitors 574:583 tight binding carbohydrate-based inhibitors 541:583 tight binding carbohydrate-based inhibitors of human OGA (hOGA) 541:603 Here we synthesize and study a series of tight binding carbohydrate-based inhibitors of human OGA (hOGA). 29997861 4 8 theme lysosomal 820:828 arg1 β-hexosaminidase 830:845 mechanistically related human lysosomal β-hexosaminidase 790:845 mechanistically related human lysosomal β-hexosaminidase 790:845 The most potent of these 2'-aminothiazolines binds with a sub-nanomolar Ki value to hOGA (510 ± 50 pM) and the most selective has greater than 1 800 000-fold selectivity for hOGA over mechanistically related human lysosomal β-hexosaminidase. 29997861 6 9 theme system 1115:1120 arg1 pKa 1083:1085 the pKa 1079:1085 the pKa of the aminothiazoline ring system 1079:1120 Using linear free energy analyses, we show binding of these 2'-aminothiazoline inhibitors depends on the pKa of the aminothiazoline ring system, revealing the protonation state of the inhibitor is a key driver of binding. 29997861 6 10 theme binding 1191:1197 arg1 driver 1181:1186 a key driver 1175:1186 a key driver of binding 1175:1197 Using linear free energy analyses, we show binding of these 2'-aminothiazoline inhibitors depends on the pKa of the aminothiazoline ring system, revealing the protonation state of the inhibitor is a key driver of binding. 29997861 6 10 theme binding 1191:1197 arg1 state 1149:1153 the protonation state 1133:1153 the protonation state of the inhibitor 1133:1170 Using linear free energy analyses, we show binding of these 2'-aminothiazoline inhibitors depends on the pKa of the aminothiazoline ring system, revealing the protonation state of the inhibitor is a key driver of binding. 29997861 3 11 theme human 588:592 arg1 hOGA 599:602 hOGA 599:602 hOGA 599:602 Here we synthesize and study a series of tight binding carbohydrate-based inhibitors of human OGA (hOGA). 29997861 3 11 theme human 588:592 arg1 OGA 594:596 human OGA 588:596 human OGA (hOGA) 588:603 Here we synthesize and study a series of tight binding carbohydrate-based inhibitors of human OGA (hOGA). 29997861 3 12 theme inhibitors 574:583 arg1 series 531:536 a series 529:536 a series of tight binding carbohydrate-based inhibitors of human OGA (hOGA) 529:603 Here we synthesize and study a series of tight binding carbohydrate-based inhibitors of human OGA (hOGA). 29997861 8 13 theme collective 1419:1428 arg1 data 1430:1433 These collective data 1413:1433 These collective data 1413:1433 These collective data support an oxazoline, rather than a protonated oxazolinium ion, intermediate being formed along the reaction pathway. 29997861 10 14 theme inhibitors 1771:1780 arg1 selectivity 1752:1762 selectivity 1752:1762 selectivity 1752:1762 The new insights gained here, into the catalytic mechanism of hOGA and the fundamental drivers of potency and selectivity of OGA inhibitors, should enable tuning of hOGA inhibitors with desirable properties. 29997861 10 14 theme inhibitors 1771:1780 arg1 potency 1740:1746 potency 1740:1746 potency 1740:1746 The new insights gained here, into the catalytic mechanism of hOGA and the fundamental drivers of potency and selectivity of OGA inhibitors, should enable tuning of hOGA inhibitors with desirable properties. 29997861 5 15 theme hOGA 897:900 arg1 homologue 902:910 an hOGA homologue 894:910 an hOGA homologue 894:910 Structural data of inhibitors in complex with an hOGA homologue reveals the basis for variation in binding among these compounds. 29997861 6 16 theme free 991:994 arg1 analyses 1003:1010 linear free energy analyses 984:1010 linear free energy analyses 984:1010 Using linear free energy analyses, we show binding of these 2'-aminothiazoline inhibitors depends on the pKa of the aminothiazoline ring system, revealing the protonation state of the inhibitor is a key driver of binding. 29997861 7 17 theme state 1311:1315 arg1 inhibitors 1285:1294 2'-aminothiazoline inhibitors 1266:1294 2'-aminothiazoline inhibitors 1266:1294 Using series of inhibitors and synthetic substrates, we show that 2'-aminothiazoline inhibitors are transition state analogues of hOGA that bind to the enzyme up to 1-million fold more tightly than the substrate. 29997861 7 17 theme state 1311:1315 arg1 analogues 1317:1325 transition state analogues 1300:1325 transition state analogues of hOGA that bind to the enzyme up to 1-million fold more tightly than the substrate 1300:1410 Using series of inhibitors and synthetic substrates, we show that 2'-aminothiazoline inhibitors are transition state analogues of hOGA that bind to the enzyme up to 1-million fold more tightly than the substrate. 29997861 0 18 theme aminothiazoline 54:68 arg1 inhibitors 70:79 tight binding aminothiazoline inhibitors 40:79 tight binding aminothiazoline inhibitors 40:79 Analysis of transition state mimicry by tight binding aminothiazoline inhibitors provides insight into catalysis by human O-GlcNAcase. 29997861 1 19 theme nucleocytoplasmic 155:171 arg1 proteins 173:180 nucleocytoplasmic proteins 155:180 nucleocytoplasmic proteins 155:180 The modification of nucleocytoplasmic proteins with O-linked N-acetylglucosamine (O-GlcNAc) plays diverse roles in multicellular organisms. 29997861 4 20 theme Ki 678:679 arg1 value 681:685 a sub-nanomolar Ki value 662:685 a sub-nanomolar Ki value 662:685 The most potent of these 2'-aminothiazolines binds with a sub-nanomolar Ki value to hOGA (510 ± 50 pM) and the most selective has greater than 1 800 000-fold selectivity for hOGA over mechanistically related human lysosomal β-hexosaminidase. 29997861 5 21 from inhibitors 867:876 arg1 complex 881:887 complex 881:887 complex with an hOGA homologue 881:910 Structural data of inhibitors in complex with an hOGA homologue reveals the basis for variation in binding among these compounds. 29997861 2 22 theme O-GlcNAc 289:296 arg1 enzyme 319:324 the enzyme 315:324 the enzyme that removes O-GlcNAc from proteins 315:360 Inhibitors of O-GlcNAc hydrolase (OGA), the enzyme that removes O-GlcNAc from proteins, lead to increased O-GlcNAc levels in cells and are seeing widespread adoption in the field as a research tool used in cells and in vivo. 29997861 2 22 theme O-GlcNAc 289:296 arg1 OGA 309:311 OGA 309:311 OGA 309:311 Inhibitors of O-GlcNAc hydrolase (OGA), the enzyme that removes O-GlcNAc from proteins, lead to increased O-GlcNAc levels in cells and are seeing widespread adoption in the field as a research tool used in cells and in vivo. 29997861 2 22 theme O-GlcNAc 289:296 arg1 hydrolase 298:306 O-GlcNAc hydrolase 289:306 O-GlcNAc hydrolase (OGA) 289:312 Inhibitors of O-GlcNAc hydrolase (OGA), the enzyme that removes O-GlcNAc from proteins, lead to increased O-GlcNAc levels in cells and are seeing widespread adoption in the field as a research tool used in cells and in vivo. 29997861 5 23 from data 859:862 arg1 complex 881:887 complex 881:887 complex with an hOGA homologue 881:910 Structural data of inhibitors in complex with an hOGA homologue reveals the basis for variation in binding among these compounds. 29997861 6 24 dep show 1016:1019 arg1 depends 1068:1074 depends 1068:1074 depends on the pKa of the aminothiazoline ring system 1068:1120 Using linear free energy analyses, we show binding of these 2'-aminothiazoline inhibitors depends on the pKa of the aminothiazoline ring system, revealing the protonation state of the inhibitor is a key driver of binding. 29997861 1 25 with modification 139:150 arg1 O-GlcNAc 217:224 O-GlcNAc 217:224 O-GlcNAc 217:224 The modification of nucleocytoplasmic proteins with O-linked N-acetylglucosamine (O-GlcNAc) plays diverse roles in multicellular organisms. 29997861 1 25 with modification 139:150 arg1 N-acetylglucosamine 196:214 O-linked N-acetylglucosamine 187:214 O-linked N-acetylglucosamine (O-GlcNAc) 187:225 The modification of nucleocytoplasmic proteins with O-linked N-acetylglucosamine (O-GlcNAc) plays diverse roles in multicellular organisms. 29997861 9 26 from series 1574:1579 arg1 Inhibitors 1553:1562 Inhibitors 1553:1562 Inhibitors from this series 1553:1579 Inhibitors from this series will prove generally useful tools for the study of O-GlcNAc. 29997861 7 27 theme transition 1300:1309 arg1 inhibitors 1285:1294 2'-aminothiazoline inhibitors 1266:1294 2'-aminothiazoline inhibitors 1266:1294 Using series of inhibitors and synthetic substrates, we show that 2'-aminothiazoline inhibitors are transition state analogues of hOGA that bind to the enzyme up to 1-million fold more tightly than the substrate. 29997861 7 27 theme transition 1300:1309 arg1 analogues 1317:1325 transition state analogues 1300:1325 transition state analogues of hOGA that bind to the enzyme up to 1-million fold more tightly than the substrate 1300:1410 Using series of inhibitors and synthetic substrates, we show that 2'-aminothiazoline inhibitors are transition state analogues of hOGA that bind to the enzyme up to 1-million fold more tightly than the substrate. 29997861 8 28 theme oxazolinium 1482:1492 arg1 ion 1494:1496 a protonated oxazolinium ion 1469:1496 a protonated oxazolinium ion 1469:1496 These collective data support an oxazoline, rather than a protonated oxazolinium ion, intermediate being formed along the reaction pathway. 29997861 1 29 link O-linked 187:194 arg1 O-GlcNAc 217:224 O-GlcNAc 217:224 O-GlcNAc 217:224 The modification of nucleocytoplasmic proteins with O-linked N-acetylglucosamine (O-GlcNAc) plays diverse roles in multicellular organisms. 29997861 1 29 link O-linked 187:194 arg1 N-acetylglucosamine 196:214 O-linked N-acetylglucosamine 187:214 O-linked N-acetylglucosamine (O-GlcNAc) 187:225 The modification of nucleocytoplasmic proteins with O-linked N-acetylglucosamine (O-GlcNAc) plays diverse roles in multicellular organisms. 29997861 5 30 from complex 881:887 arg1 data 859:862 Structural data 848:862 Structural data of inhibitors in complex with an hOGA homologue 848:910 Structural data of inhibitors in complex with an hOGA homologue reveals the basis for variation in binding among these compounds. 29997861 6 31 theme inhibitor 1162:1170 arg1 driver 1181:1186 a key driver 1175:1186 a key driver of binding 1175:1197 Using linear free energy analyses, we show binding of these 2'-aminothiazoline inhibitors depends on the pKa of the aminothiazoline ring system, revealing the protonation state of the inhibitor is a key driver of binding. 29997861 6 31 theme inhibitor 1162:1170 arg1 state 1149:1153 the protonation state 1133:1153 the protonation state of the inhibitor 1133:1170 Using linear free energy analyses, we show binding of these 2'-aminothiazoline inhibitors depends on the pKa of the aminothiazoline ring system, revealing the protonation state of the inhibitor is a key driver of binding. 29997861 0 32 theme transition 12:21 arg1 mimicry 29:35 transition state mimicry 12:35 transition state mimicry 12:35 Analysis of transition state mimicry by tight binding aminothiazoline inhibitors provides insight into catalysis by human O-GlcNAcase. 29997861 0 33 theme mimicry 29:35 arg1 Analysis 0:7 Analysis 0:7 Analysis of transition state mimicry by tight binding aminothiazoline inhibitors 0:79 Analysis of transition state mimicry by tight binding aminothiazoline inhibitors provides insight into catalysis by human O-GlcNAcase. 29997861 2 34 theme research 459:466 arg1 tool 468:471 a research tool 457:471 a research tool used in cells and in vivo 457:497 Inhibitors of O-GlcNAc hydrolase (OGA), the enzyme that removes O-GlcNAc from proteins, lead to increased O-GlcNAc levels in cells and are seeing widespread adoption in the field as a research tool used in cells and in vivo. 29997861 2 34 theme research 459:466 arg1 cells 481:485 cells 481:485 cells 481:485 Inhibitors of O-GlcNAc hydrolase (OGA), the enzyme that removes O-GlcNAc from proteins, lead to increased O-GlcNAc levels in cells and are seeing widespread adoption in the field as a research tool used in cells and in vivo. 29997861 2 34 theme research 459:466 arg1 vivo 494:497 vivo 494:497 vivo 494:497 Inhibitors of O-GlcNAc hydrolase (OGA), the enzyme that removes O-GlcNAc from proteins, lead to increased O-GlcNAc levels in cells and are seeing widespread adoption in the field as a research tool used in cells and in vivo. 29997861 2 34 theme research 459:466 arg1 adoption 432:439 widespread adoption 421:439 widespread adoption in the field 421:452 Inhibitors of O-GlcNAc hydrolase (OGA), the enzyme that removes O-GlcNAc from proteins, lead to increased O-GlcNAc levels in cells and are seeing widespread adoption in the field as a research tool used in cells and in vivo. 29997861 0 35 theme tight 40:44 arg1 inhibitors 70:79 tight binding aminothiazoline inhibitors 40:79 tight binding aminothiazoline inhibitors 40:79 Analysis of transition state mimicry by tight binding aminothiazoline inhibitors provides insight into catalysis by human O-GlcNAcase. 29997861 7 36 theme substrates 1241:1250 arg1 series 1206:1211 series 1206:1211 series of inhibitors and synthetic substrates 1206:1250 Using series of inhibitors and synthetic substrates, we show that 2'-aminothiazoline inhibitors are transition state analogues of hOGA that bind to the enzyme up to 1-million fold more tightly than the substrate. 29997861 8 37 theme reaction 1535:1542 arg1 pathway 1544:1550 the reaction pathway 1531:1550 the reaction pathway 1531:1550 These collective data support an oxazoline, rather than a protonated oxazolinium ion, intermediate being formed along the reaction pathway. 29997861 10 38 theme new 1646:1648 arg1 insights 1650:1657 The new insights 1642:1657 The new insights 1642:1657 The new insights gained here, into the catalytic mechanism of hOGA and the fundamental drivers of potency and selectivity of OGA inhibitors, should enable tuning of hOGA inhibitors with desirable properties. 29997861 3 39 theme OGA 594:596 arg1 inhibitors 574:583 tight binding carbohydrate-based inhibitors 541:583 tight binding carbohydrate-based inhibitors of human OGA (hOGA) 541:603 Here we synthesize and study a series of tight binding carbohydrate-based inhibitors of human OGA (hOGA). 29997861 10 40 with tuning 1797:1802 arg1 properties 1838:1847 desirable properties 1828:1847 desirable properties 1828:1847 The new insights gained here, into the catalytic mechanism of hOGA and the fundamental drivers of potency and selectivity of OGA inhibitors, should enable tuning of hOGA inhibitors with desirable properties. 29997861 10 41 theme hOGA 1807:1810 arg1 inhibitors 1812:1821 hOGA inhibitors 1807:1821 hOGA inhibitors 1807:1821 The new insights gained here, into the catalytic mechanism of hOGA and the fundamental drivers of potency and selectivity of OGA inhibitors, should enable tuning of hOGA inhibitors with desirable properties. 29997861 4 42 theme than 744:747 arg1 selectivity 764:774 greater than 1 800 000-fold selectivity 736:774 greater than 1 800 000-fold selectivity for hOGA over mechanistically related human lysosomal β-hexosaminidase 736:845 The most potent of these 2'-aminothiazolines binds with a sub-nanomolar Ki value to hOGA (510 ± 50 pM) and the most selective has greater than 1 800 000-fold selectivity for hOGA over mechanistically related human lysosomal β-hexosaminidase. 29997861 2 43 theme O-GlcNAc 381:388 arg1 levels 390:395 increased O-GlcNAc levels 371:395 increased O-GlcNAc levels in cells 371:404 Inhibitors of O-GlcNAc hydrolase (OGA), the enzyme that removes O-GlcNAc from proteins, lead to increased O-GlcNAc levels in cells and are seeing widespread adoption in the field as a research tool used in cells and in vivo. 29997861 2 44 from adoption 432:439 arg1 field 448:452 the field 444:452 the field 444:452 Inhibitors of O-GlcNAc hydrolase (OGA), the enzyme that removes O-GlcNAc from proteins, lead to increased O-GlcNAc levels in cells and are seeing widespread adoption in the field as a research tool used in cells and in vivo. 29997861 9 45 theme O-GlcNAc 1632:1639 arg1 study 1623:1627 the study 1619:1627 the study of O-GlcNAc 1619:1639 Inhibitors from this series will prove generally useful tools for the study of O-GlcNAc. 29997861 6 46 theme inhibitors 1057:1066 arg1 binding 1021:1027 binding 1021:1027 binding of these 2'-aminothiazoline inhibitors 1021:1066 Using linear free energy analyses, we show binding of these 2'-aminothiazoline inhibitors depends on the pKa of the aminothiazoline ring system, revealing the protonation state of the inhibitor is a key driver of binding. 29997861 10 47 theme hOGA 1704:1707 arg1 mechanism 1691:1699 the catalytic mechanism 1677:1699 the catalytic mechanism of hOGA 1677:1707 The new insights gained here, into the catalytic mechanism of hOGA and the fundamental drivers of potency and selectivity of OGA inhibitors, should enable tuning of hOGA inhibitors with desirable properties. 29997861 10 47 theme hOGA 1704:1707 arg1 drivers 1729:1735 the fundamental drivers 1713:1735 the fundamental drivers of potency and selectivity of OGA inhibitors 1713:1780 The new insights gained here, into the catalytic mechanism of hOGA and the fundamental drivers of potency and selectivity of OGA inhibitors, should enable tuning of hOGA inhibitors with desirable properties. 29997861 5 48 from variation 934:942 arg1 binding 947:953 binding 947:953 binding 947:953 Structural data of inhibitors in complex with an hOGA homologue reveals the basis for variation in binding among these compounds. 29997861 5 49 theme inhibitors 867:876 arg1 data 859:862 Structural data 848:862 Structural data of inhibitors in complex with an hOGA homologue 848:910 Structural data of inhibitors in complex with an hOGA homologue reveals the basis for variation in binding among these compounds. 29997861 6 50 theme aminothiazoline 1094:1108 arg1 system 1115:1120 the aminothiazoline ring system 1090:1120 the aminothiazoline ring system 1090:1120 Using linear free energy analyses, we show binding of these 2'-aminothiazoline inhibitors depends on the pKa of the aminothiazoline ring system, revealing the protonation state of the inhibitor is a key driver of binding. 29997861 1 51 theme O-linked 187:194 arg1 O-GlcNAc 217:224 O-GlcNAc 217:224 O-GlcNAc 217:224 The modification of nucleocytoplasmic proteins with O-linked N-acetylglucosamine (O-GlcNAc) plays diverse roles in multicellular organisms. 29997861 1 51 theme O-linked 187:194 arg1 N-acetylglucosamine 196:214 O-linked N-acetylglucosamine 187:214 O-linked N-acetylglucosamine (O-GlcNAc) 187:225 The modification of nucleocytoplasmic proteins with O-linked N-acetylglucosamine (O-GlcNAc) plays diverse roles in multicellular organisms. 29997861 3 52 theme tight 541:545 arg1 inhibitors 574:583 tight binding carbohydrate-based inhibitors 541:583 tight binding carbohydrate-based inhibitors of human OGA (hOGA) 541:603 Here we synthesize and study a series of tight binding carbohydrate-based inhibitors of human OGA (hOGA). 29997861 4 53 theme related 806:812 arg1 β-hexosaminidase 830:845 mechanistically related human lysosomal β-hexosaminidase 790:845 mechanistically related human lysosomal β-hexosaminidase 790:845 The most potent of these 2'-aminothiazolines binds with a sub-nanomolar Ki value to hOGA (510 ± 50 pM) and the most selective has greater than 1 800 000-fold selectivity for hOGA over mechanistically related human lysosomal β-hexosaminidase. 29997861 7 54 theme 1-million 1365:1373 arg1 fold 1375:1378 1-million fold 1365:1378 1-million fold 1365:1378 Using series of inhibitors and synthetic substrates, we show that 2'-aminothiazoline inhibitors are transition state analogues of hOGA that bind to the enzyme up to 1-million fold more tightly than the substrate. 29997861 4 55 theme 2'-aminothiazolines 631:649 arg1 potent 615:620 potent 615:620 potent 615:620 The most potent of these 2'-aminothiazolines binds with a sub-nanomolar Ki value to hOGA (510 ± 50 pM) and the most selective has greater than 1 800 000-fold selectivity for hOGA over mechanistically related human lysosomal β-hexosaminidase. 29997861 10 56 theme fundamental 1717:1727 arg1 drivers 1729:1735 the fundamental drivers 1713:1735 the fundamental drivers of potency and selectivity of OGA inhibitors 1713:1780 The new insights gained here, into the catalytic mechanism of hOGA and the fundamental drivers of potency and selectivity of OGA inhibitors, should enable tuning of hOGA inhibitors with desirable properties. 29997861 6 57 theme ring 1110:1113 arg1 system 1115:1120 the aminothiazoline ring system 1090:1120 the aminothiazoline ring system 1090:1120 Using linear free energy analyses, we show binding of these 2'-aminothiazoline inhibitors depends on the pKa of the aminothiazoline ring system, revealing the protonation state of the inhibitor is a key driver of binding. 29997861 10 58 theme selectivity 1752:1762 arg1 mechanism 1691:1699 the catalytic mechanism 1677:1699 the catalytic mechanism of hOGA 1677:1707 The new insights gained here, into the catalytic mechanism of hOGA and the fundamental drivers of potency and selectivity of OGA inhibitors, should enable tuning of hOGA inhibitors with desirable properties. 29997861 10 58 theme selectivity 1752:1762 arg1 drivers 1729:1735 the fundamental drivers 1713:1735 the fundamental drivers of potency and selectivity of OGA inhibitors 1713:1780 The new insights gained here, into the catalytic mechanism of hOGA and the fundamental drivers of potency and selectivity of OGA inhibitors, should enable tuning of hOGA inhibitors with desirable properties. 29997861 5 59 theme Structural 848:857 arg1 data 859:862 Structural data 848:862 Structural data of inhibitors in complex with an hOGA homologue 848:910 Structural data of inhibitors in complex with an hOGA homologue reveals the basis for variation in binding among these compounds. 29997861 1 60 theme diverse 233:239 arg1 roles 241:245 diverse roles 233:245 diverse roles 233:245 The modification of nucleocytoplasmic proteins with O-linked N-acetylglucosamine (O-GlcNAc) plays diverse roles in multicellular organisms. 29997861 10 61 theme potency 1740:1746 arg1 mechanism 1691:1699 the catalytic mechanism 1677:1699 the catalytic mechanism of hOGA 1677:1707 The new insights gained here, into the catalytic mechanism of hOGA and the fundamental drivers of potency and selectivity of OGA inhibitors, should enable tuning of hOGA inhibitors with desirable properties. 29997861 10 61 theme potency 1740:1746 arg1 drivers 1729:1735 the fundamental drivers 1713:1735 the fundamental drivers of potency and selectivity of OGA inhibitors 1713:1780 The new insights gained here, into the catalytic mechanism of hOGA and the fundamental drivers of potency and selectivity of OGA inhibitors, should enable tuning of hOGA inhibitors with desirable properties. 29997861 6 62 theme key 1177:1179 arg1 driver 1181:1186 a key driver 1175:1186 a key driver of binding 1175:1197 Using linear free energy analyses, we show binding of these 2'-aminothiazoline inhibitors depends on the pKa of the aminothiazoline ring system, revealing the protonation state of the inhibitor is a key driver of binding. 29997861 6 62 theme key 1177:1179 arg1 state 1149:1153 the protonation state 1133:1153 the protonation state of the inhibitor 1133:1170 Using linear free energy analyses, we show binding of these 2'-aminothiazoline inhibitors depends on the pKa of the aminothiazoline ring system, revealing the protonation state of the inhibitor is a key driver of binding. 29997861 2 63 theme hydrolase 298:306 arg1 Inhibitors 275:284 Inhibitors 275:284 Inhibitors of O-GlcNAc hydrolase (OGA), the enzyme that removes O-GlcNAc from proteins, 275:361 Inhibitors of O-GlcNAc hydrolase (OGA), the enzyme that removes O-GlcNAc from proteins, lead to increased O-GlcNAc levels in cells and are seeing widespread adoption in the field as a research tool used in cells and in vivo. 29997861 7 64 theme enzyme 1352:1357 arg1 up 1359:1360 the enzyme up 1348:1360 the enzyme up to 1-million fold 1348:1378 Using series of inhibitors and synthetic substrates, we show that 2'-aminothiazoline inhibitors are transition state analogues of hOGA that bind to the enzyme up to 1-million fold more tightly than the substrate. 29997861 6 65 theme energy 996:1001 arg1 analyses 1003:1010 linear free energy analyses 984:1010 linear free energy analyses 984:1010 Using linear free energy analyses, we show binding of these 2'-aminothiazoline inhibitors depends on the pKa of the aminothiazoline ring system, revealing the protonation state of the inhibitor is a key driver of binding. 29997861 7 66 theme hOGA 1330:1333 arg1 inhibitors 1285:1294 2'-aminothiazoline inhibitors 1266:1294 2'-aminothiazoline inhibitors 1266:1294 Using series of inhibitors and synthetic substrates, we show that 2'-aminothiazoline inhibitors are transition state analogues of hOGA that bind to the enzyme up to 1-million fold more tightly than the substrate. 29997861 7 66 theme hOGA 1330:1333 arg1 analogues 1317:1325 transition state analogues 1300:1325 transition state analogues of hOGA that bind to the enzyme up to 1-million fold more tightly than the substrate 1300:1410 Using series of inhibitors and synthetic substrates, we show that 2'-aminothiazoline inhibitors are transition state analogues of hOGA that bind to the enzyme up to 1-million fold more tightly than the substrate. 29997861 10 67 theme OGA 1767:1769 arg1 inhibitors 1771:1780 OGA inhibitors 1767:1780 OGA inhibitors 1767:1780 The new insights gained here, into the catalytic mechanism of hOGA and the fundamental drivers of potency and selectivity of OGA inhibitors, should enable tuning of hOGA inhibitors with desirable properties. 29997861 6 68 theme linear 984:989 arg1 analyses 1003:1010 linear free energy analyses 984:1010 linear free energy analyses 984:1010 Using linear free energy analyses, we show binding of these 2'-aminothiazoline inhibitors depends on the pKa of the aminothiazoline ring system, revealing the protonation state of the inhibitor is a key driver of binding. 29997861 4 69 contain has 732:734 arg1 selective 722:730 selective 722:730 selective 722:730 The most potent of these 2'-aminothiazolines binds with a sub-nanomolar Ki value to hOGA (510 ± 50 pM) and the most selective has greater than 1 800 000-fold selectivity for hOGA over mechanistically related human lysosomal β-hexosaminidase. 29997861 4 69 contain has 732:734 arg2 selectivity 764:774 greater than 1 800 000-fold selectivity 736:774 greater than 1 800 000-fold selectivity for hOGA over mechanistically related human lysosomal β-hexosaminidase 736:845 The most potent of these 2'-aminothiazolines binds with a sub-nanomolar Ki value to hOGA (510 ± 50 pM) and the most selective has greater than 1 800 000-fold selectivity for hOGA over mechanistically related human lysosomal β-hexosaminidase. 29997861 1 70 theme proteins 173:180 arg1 modification 139:150 The modification 135:150 The modification of nucleocytoplasmic proteins with O-linked N-acetylglucosamine (O-GlcNAc) 135:225 The modification of nucleocytoplasmic proteins with O-linked N-acetylglucosamine (O-GlcNAc) plays diverse roles in multicellular organisms. 29997861 4 71 theme sub-nanomolar 664:676 arg1 value 681:685 a sub-nanomolar Ki value 662:685 a sub-nanomolar Ki value 662:685 The most potent of these 2'-aminothiazolines binds with a sub-nanomolar Ki value to hOGA (510 ± 50 pM) and the most selective has greater than 1 800 000-fold selectivity for hOGA over mechanistically related human lysosomal β-hexosaminidase. 29997861 2 72 dep used 473:476 arg1 tool 468:471 a research tool 457:471 a research tool used in cells and in vivo 457:497 Inhibitors of O-GlcNAc hydrolase (OGA), the enzyme that removes O-GlcNAc from proteins, lead to increased O-GlcNAc levels in cells and are seeing widespread adoption in the field as a research tool used in cells and in vivo. 29997861 2 72 dep used 473:476 arg1 cells 481:485 cells 481:485 cells 481:485 Inhibitors of O-GlcNAc hydrolase (OGA), the enzyme that removes O-GlcNAc from proteins, lead to increased O-GlcNAc levels in cells and are seeing widespread adoption in the field as a research tool used in cells and in vivo. 29997861 2 72 dep used 473:476 arg1 vivo 494:497 vivo 494:497 vivo 494:497 Inhibitors of O-GlcNAc hydrolase (OGA), the enzyme that removes O-GlcNAc from proteins, lead to increased O-GlcNAc levels in cells and are seeing widespread adoption in the field as a research tool used in cells and in vivo. 29997861 8 73 theme protonated 1471:1480 arg1 ion 1494:1496 a protonated oxazolinium ion 1469:1496 a protonated oxazolinium ion 1469:1496 These collective data support an oxazoline, rather than a protonated oxazolinium ion, intermediate being formed along the reaction pathway. 29997861 0 74 theme human 116:120 arg1 O-GlcNAcase 122:132 human O-GlcNAcase 116:132 human O-GlcNAcase 116:132 Analysis of transition state mimicry by tight binding aminothiazoline inhibitors provides insight into catalysis by human O-GlcNAcase. 29997861 6 75 theme 2'-aminothiazoline 1038:1055 arg1 inhibitors 1057:1066 these 2'-aminothiazoline inhibitors 1032:1066 these 2'-aminothiazoline inhibitors 1032:1066 Using linear free energy analyses, we show binding of these 2'-aminothiazoline inhibitors depends on the pKa of the aminothiazoline ring system, revealing the protonation state of the inhibitor is a key driver of binding. 29997861 7 76 theme 2'-aminothiazoline 1266:1283 arg1 inhibitors 1285:1294 2'-aminothiazoline inhibitors 1266:1294 2'-aminothiazoline inhibitors 1266:1294 Using series of inhibitors and synthetic substrates, we show that 2'-aminothiazoline inhibitors are transition state analogues of hOGA that bind to the enzyme up to 1-million fold more tightly than the substrate. 29997861 7 76 theme 2'-aminothiazoline 1266:1283 arg1 analogues 1317:1325 transition state analogues 1300:1325 transition state analogues of hOGA that bind to the enzyme up to 1-million fold more tightly than the substrate 1300:1410 Using series of inhibitors and synthetic substrates, we show that 2'-aminothiazoline inhibitors are transition state analogues of hOGA that bind to the enzyme up to 1-million fold more tightly than the substrate. 29997861 4 77 theme 510 696:698 arg1 ± 700:700 ± 700:700 ± 700:700 The most potent of these 2'-aminothiazolines binds with a sub-nanomolar Ki value to hOGA (510 ± 50 pM) and the most selective has greater than 1 800 000-fold selectivity for hOGA over mechanistically related human lysosomal β-hexosaminidase. 29997861 0 78 theme state 23:27 arg1 mimicry 29:35 transition state mimicry 12:35 transition state mimicry 12:35 Analysis of transition state mimicry by tight binding aminothiazoline inhibitors provides insight into catalysis by human O-GlcNAcase. 29997861 4 79 theme 50 702:703 arg1 ± 700:700 ± 700:700 ± 700:700 The most potent of these 2'-aminothiazolines binds with a sub-nanomolar Ki value to hOGA (510 ± 50 pM) and the most selective has greater than 1 800 000-fold selectivity for hOGA over mechanistically related human lysosomal β-hexosaminidase. 29997861 2 80 theme widespread 421:430 arg1 tool 468:471 a research tool 457:471 a research tool used in cells and in vivo 457:497 Inhibitors of O-GlcNAc hydrolase (OGA), the enzyme that removes O-GlcNAc from proteins, lead to increased O-GlcNAc levels in cells and are seeing widespread adoption in the field as a research tool used in cells and in vivo. 29997861 2 80 theme widespread 421:430 arg1 adoption 432:439 widespread adoption 421:439 widespread adoption in the field 421:452 Inhibitors of O-GlcNAc hydrolase (OGA), the enzyme that removes O-GlcNAc from proteins, lead to increased O-GlcNAc levels in cells and are seeing widespread adoption in the field as a research tool used in cells and in vivo. 29997861 4 81 theme 1 800 000-fold 749:762 arg1 selectivity 764:774 greater than 1 800 000-fold selectivity 736:774 greater than 1 800 000-fold selectivity for hOGA over mechanistically related human lysosomal β-hexosaminidase 736:845 The most potent of these 2'-aminothiazolines binds with a sub-nanomolar Ki value to hOGA (510 ± 50 pM) and the most selective has greater than 1 800 000-fold selectivity for hOGA over mechanistically related human lysosomal β-hexosaminidase. 29997861 0 82 theme binding 46:52 arg1 inhibitors 70:79 tight binding aminothiazoline inhibitors 40:79 tight binding aminothiazoline inhibitors 40:79 Analysis of transition state mimicry by tight binding aminothiazoline inhibitors provides insight into catalysis by human O-GlcNAcase. 29997861 2 83 from levels 390:395 arg1 cells 400:404 cells 400:404 cells 400:404 Inhibitors of O-GlcNAc hydrolase (OGA), the enzyme that removes O-GlcNAc from proteins, lead to increased O-GlcNAc levels in cells and are seeing widespread adoption in the field as a research tool used in cells and in vivo. 29997861 7 84 theme synthetic 1231:1239 arg1 substrates 1241:1250 synthetic substrates 1231:1250 synthetic substrates 1231:1250 Using series of inhibitors and synthetic substrates, we show that 2'-aminothiazoline inhibitors are transition state analogues of hOGA that bind to the enzyme up to 1-million fold more tightly than the substrate. 29997861 10 85 theme desirable 1828:1836 arg1 properties 1838:1847 desirable properties 1828:1847 desirable properties 1828:1847 The new insights gained here, into the catalytic mechanism of hOGA and the fundamental drivers of potency and selectivity of OGA inhibitors, should enable tuning of hOGA inhibitors with desirable properties. 29997861 7 86 theme inhibitors 1216:1225 arg1 series 1206:1211 series 1206:1211 series of inhibitors and synthetic substrates 1206:1250 Using series of inhibitors and synthetic substrates, we show that 2'-aminothiazoline inhibitors are transition state analogues of hOGA that bind to the enzyme up to 1-million fold more tightly than the substrate. 29997861 10 87 theme inhibitors 1812:1821 arg1 tuning 1797:1802 tuning 1797:1802 tuning of hOGA inhibitors with desirable properties 1797:1847 The new insights gained here, into the catalytic mechanism of hOGA and the fundamental drivers of potency and selectivity of OGA inhibitors, should enable tuning of hOGA inhibitors with desirable properties. 29997861 1 88 theme multicellular 250:262 arg1 organisms 264:272 multicellular organisms 250:272 multicellular organisms 250:272 The modification of nucleocytoplasmic proteins with O-linked N-acetylglucosamine (O-GlcNAc) plays diverse roles in multicellular organisms. 29997861 4 89 theme greater 736:742 arg1 selectivity 764:774 greater than 1 800 000-fold selectivity 736:774 greater than 1 800 000-fold selectivity for hOGA over mechanistically related human lysosomal β-hexosaminidase 736:845 The most potent of these 2'-aminothiazolines binds with a sub-nanomolar Ki value to hOGA (510 ± 50 pM) and the most selective has greater than 1 800 000-fold selectivity for hOGA over mechanistically related human lysosomal β-hexosaminidase. 29997861 2 90 theme increased 371:379 arg1 levels 390:395 increased O-GlcNAc levels 371:395 increased O-GlcNAc levels in cells 371:404 Inhibitors of O-GlcNAc hydrolase (OGA), the enzyme that removes O-GlcNAc from proteins, lead to increased O-GlcNAc levels in cells and are seeing widespread adoption in the field as a research tool used in cells and in vivo. 28209512 0 0 theme lipid 105:109 arg1 rafts 111:115 lipid rafts 105:115 lipid rafts 105:115 N-glycan-dependent cell-surface expression of the P2Y2 receptor and N-glycan-independent distribution to lipid rafts. 28209512 5 1 from blotting 610:617 arg1 cells 692:696 COS-7 cells 686:696 COS-7 cells 686:696 Western blotting of the wild type (WT) protein and mutants (N9Q, N13Q, N9Q/N13Q) in COS-7 cells showed that both Asn residues were glycosylated in the WT. 28209512 5 2 theme type 631:634 arg1 protein 641:647 the wild type (WT) protein 622:647 the wild type (WT) protein 622:647 Western blotting of the wild type (WT) protein and mutants (N9Q, N13Q, N9Q/N13Q) in COS-7 cells showed that both Asn residues were glycosylated in the WT. 28209512 6 3 theme endoplasmic 840:850 arg1 ER 863:864 ER 863:864 ER 863:864 Fluorescent microscopy analysis showed that WT, N9Q and N13Q were expressed in the endoplasmic reticulum (ER), Golgi body, and cell membrane, but N9Q/N13Q was only found in the ER. 28209512 6 3 theme endoplasmic 840:850 arg1 reticulum 852:860 the endoplasmic reticulum 836:860 the endoplasmic reticulum (ER) 836:865 Fluorescent microscopy analysis showed that WT, N9Q and N13Q were expressed in the endoplasmic reticulum (ER), Golgi body, and cell membrane, but N9Q/N13Q was only found in the ER. 28209512 4 4 theme Asn 490:492 arg1 residues 494:501 the two consensus Asn residues 472:501 the two consensus Asn residues for N-glycosylation 472:521 In this study, we prepared N-glycan-deficient mutants by mutating the two consensus Asn residues for N-glycosylation to Gln to examine intracellular localization and association with lipid rafts. 28209512 9 5 theme subsequent 1285:1294 arg1 expression 1296:1305 subsequent expression 1285:1305 subsequent expression in the cell membrane 1285:1326 These findings suggest that P2Y2R is localized in lipid rafts in the ER during biosynthesis, and that N-glycosylation is required for subsequent expression in the cell membrane. 28209512 10 6 theme N9Q/N13Q 1433:1440 arg1 level 1424:1428 the level 1420:1428 the level of N9Q/N13Q 1420:1440 In the presence of epoxomicin, a proteasome inhibitor, there was a significant increase in the level of N9Q/N13Q, which suggests that N-glycan-deficient P2Y2R undergoes proteasomal degradation. 28209512 4 7 theme consensus 480:488 arg1 residues 494:501 the two consensus Asn residues 472:501 the two consensus Asn residues for N-glycosylation 472:521 In this study, we prepared N-glycan-deficient mutants by mutating the two consensus Asn residues for N-glycosylation to Gln to examine intracellular localization and association with lipid rafts. 28209512 7 8 theme cell 970:973 arg1 surface 975:981 the cell surface 966:981 the cell surface 966:981 WT, N9Q and N13Q moved from the cell surface to endosomes within 15 min after UTP stimulation. 28209512 3 9 with interaction 362:372 arg1 molecules 395:403 other signaling molecules 379:403 other signaling molecules 379:403 Some GPCRs are localized in lipid rafts for interaction with other signaling molecules. 28209512 10 10 dep epoxomicin 1348:1357 arg1 the 1332:1334 the 1332:1334 the 1332:1334 In the presence of epoxomicin, a proteasome inhibitor, there was a significant increase in the level of N9Q/N13Q, which suggests that N-glycan-deficient P2Y2R undergoes proteasomal degradation. 28209512 10 10 dep epoxomicin 1348:1357 arg1 presence 1336:1343 presence 1336:1343 presence 1336:1343 In the presence of epoxomicin, a proteasome inhibitor, there was a significant increase in the level of N9Q/N13Q, which suggests that N-glycan-deficient P2Y2R undergoes proteasomal degradation. 28209512 6 11 theme cell 884:887 arg1 membrane 889:896 cell membrane 884:896 cell membrane 884:896 Fluorescent microscopy analysis showed that WT, N9Q and N13Q were expressed in the endoplasmic reticulum (ER), Golgi body, and cell membrane, but N9Q/N13Q was only found in the ER. 28209512 4 12 theme N-glycan-deficient 433:450 arg1 mutants 452:458 N-glycan-deficient mutants 433:458 N-glycan-deficient mutants 433:458 In this study, we prepared N-glycan-deficient mutants by mutating the two consensus Asn residues for N-glycosylation to Gln to examine intracellular localization and association with lipid rafts. 28209512 5 13 theme Western 602:608 arg1 blotting 610:617 Western blotting 602:617 Western blotting of the wild type (WT) protein 602:647 Western blotting of the wild type (WT) protein and mutants (N9Q, N13Q, N9Q/N13Q) in COS-7 cells showed that both Asn residues were glycosylated in the WT. 28209512 8 14 theme glycosylation-deficient 1053:1075 arg1 mutant 1077:1082 the N9Q/N13Q glycosylation-deficient mutant 1040:1082 the N9Q/N13Q glycosylation-deficient mutant 1040:1082 WT and the N9Q/N13Q glycosylation-deficient mutant appeared in the detergent insoluble membrane fraction, lipid raft. 28209512 8 15 theme membrane 1120:1127 arg1 fraction 1129:1136 the detergent insoluble membrane fraction 1096:1136 the detergent insoluble membrane fraction 1096:1136 WT and the N9Q/N13Q glycosylation-deficient mutant appeared in the detergent insoluble membrane fraction, lipid raft. 28209512 8 15 theme membrane 1120:1127 arg1 raft 1145:1148 lipid raft 1139:1148 lipid raft 1139:1148 WT and the N9Q/N13Q glycosylation-deficient mutant appeared in the detergent insoluble membrane fraction, lipid raft. 28209512 5 16 theme COS-7 686:690 arg1 cells 692:696 COS-7 cells 686:696 COS-7 cells 686:696 Western blotting of the wild type (WT) protein and mutants (N9Q, N13Q, N9Q/N13Q) in COS-7 cells showed that both Asn residues were glycosylated in the WT. 28209512 0 17 theme P2Y2 50:53 arg1 receptor 55:62 the P2Y2 receptor 46:62 the P2Y2 receptor 46:62 N-glycan-dependent cell-surface expression of the P2Y2 receptor and N-glycan-independent distribution to lipid rafts. 28209512 8 18 theme insoluble 1110:1118 arg1 fraction 1129:1136 the detergent insoluble membrane fraction 1096:1136 the detergent insoluble membrane fraction 1096:1136 WT and the N9Q/N13Q glycosylation-deficient mutant appeared in the detergent insoluble membrane fraction, lipid raft. 28209512 8 18 theme insoluble 1110:1118 arg1 raft 1145:1148 lipid raft 1139:1148 lipid raft 1139:1148 WT and the N9Q/N13Q glycosylation-deficient mutant appeared in the detergent insoluble membrane fraction, lipid raft. 28209512 0 19 theme cell-surface 19:30 arg1 expression 32:41 N-glycan-dependent cell-surface expression 0:41 N-glycan-dependent cell-surface expression of the P2Y2 receptor 0:62 N-glycan-dependent cell-surface expression of the P2Y2 receptor and N-glycan-independent distribution to lipid rafts. 28209512 9 20 theme lipid 1201:1205 arg1 rafts 1207:1211 lipid rafts 1201:1211 lipid rafts in the ER during biosynthesis 1201:1241 These findings suggest that P2Y2R is localized in lipid rafts in the ER during biosynthesis, and that N-glycosylation is required for subsequent expression in the cell membrane. 28209512 9 21 from rafts 1207:1211 arg1 localized 1188:1196 localized 1188:1196 localized 1188:1196 These findings suggest that P2Y2R is localized in lipid rafts in the ER during biosynthesis, and that N-glycosylation is required for subsequent expression in the cell membrane. 28209512 9 21 from rafts 1207:1211 arg1 ER 1220:1221 the ER 1216:1221 the ER during biosynthesis 1216:1241 These findings suggest that P2Y2R is localized in lipid rafts in the ER during biosynthesis, and that N-glycosylation is required for subsequent expression in the cell membrane. 28209512 9 22 from localized 1188:1196 arg1 rafts 1207:1211 lipid rafts 1201:1211 lipid rafts in the ER during biosynthesis 1201:1241 These findings suggest that P2Y2R is localized in lipid rafts in the ER during biosynthesis, and that N-glycosylation is required for subsequent expression in the cell membrane. 28209512 0 23 theme N-glycan-dependent 0:17 arg1 expression 32:41 N-glycan-dependent cell-surface expression 0:41 N-glycan-dependent cell-surface expression of the P2Y2 receptor 0:62 N-glycan-dependent cell-surface expression of the P2Y2 receptor and N-glycan-independent distribution to lipid rafts. 28209512 10 24 theme N-glycan-deficient 1463:1480 arg1 P2Y2R 1482:1486 N-glycan-deficient P2Y2R 1463:1486 N-glycan-deficient P2Y2R 1463:1486 In the presence of epoxomicin, a proteasome inhibitor, there was a significant increase in the level of N9Q/N13Q, which suggests that N-glycan-deficient P2Y2R undergoes proteasomal degradation. 28209512 5 25 theme wild 626:629 arg1 WT 637:638 WT 637:638 WT 637:638 Western blotting of the wild type (WT) protein and mutants (N9Q, N13Q, N9Q/N13Q) in COS-7 cells showed that both Asn residues were glycosylated in the WT. 28209512 5 25 theme wild 626:629 arg1 type 631:634 wild type 626:634 the wild type (WT) protein 622:647 Western blotting of the wild type (WT) protein and mutants (N9Q, N13Q, N9Q/N13Q) in COS-7 cells showed that both Asn residues were glycosylated in the WT. 28209512 6 26 located found 921:925 arg1 ER 934:935 the ER 930:935 the ER 930:935 Fluorescent microscopy analysis showed that WT, N9Q and N13Q were expressed in the endoplasmic reticulum (ER), Golgi body, and cell membrane, but N9Q/N13Q was only found in the ER. 28209512 6 26 located found 921:925 arg2 N9Q/N13Q 903:910 N9Q/N13Q 903:910 N9Q/N13Q 903:910 Fluorescent microscopy analysis showed that WT, N9Q and N13Q were expressed in the endoplasmic reticulum (ER), Golgi body, and cell membrane, but N9Q/N13Q was only found in the ER. 28209512 9 27 from expression 1296:1305 arg1 membrane 1319:1326 the cell membrane 1310:1326 the cell membrane 1310:1326 These findings suggest that P2Y2R is localized in lipid rafts in the ER during biosynthesis, and that N-glycosylation is required for subsequent expression in the cell membrane. 28209512 1 28 theme P2Y2 118:121 arg1 receptor 163:170 a G-protein-coupled receptor 143:170 a G-protein-coupled receptor (GPCR) that couples with Gαq/11 and is stimulated by ATP and UTP 143:235 P2Y2 receptor (P2Y2R) is a G-protein-coupled receptor (GPCR) that couples with Gαq/11 and is stimulated by ATP and UTP. 28209512 1 28 theme P2Y2 118:121 arg1 P2Y2R 133:137 P2Y2R 133:137 P2Y2R 133:137 P2Y2 receptor (P2Y2R) is a G-protein-coupled receptor (GPCR) that couples with Gαq/11 and is stimulated by ATP and UTP. 28209512 1 28 theme P2Y2 118:121 arg1 receptor 123:130 P2Y2 receptor 118:130 P2Y2 receptor (P2Y2R) 118:138 P2Y2 receptor (P2Y2R) is a G-protein-coupled receptor (GPCR) that couples with Gαq/11 and is stimulated by ATP and UTP. 28209512 3 29 theme lipid 346:350 arg1 rafts 352:356 lipid rafts 346:356 lipid rafts for interaction with other signaling molecules 346:403 Some GPCRs are localized in lipid rafts for interaction with other signaling molecules. 28209512 4 30 theme intracellular 541:553 arg1 localization 555:566 intracellular localization 541:566 intracellular localization 541:566 In this study, we prepared N-glycan-deficient mutants by mutating the two consensus Asn residues for N-glycosylation to Gln to examine intracellular localization and association with lipid rafts. 28209512 2 31 theme proinflammatory 265:279 arg1 changes 281:287 proinflammatory changes 265:287 proinflammatory changes 265:287 P2Y2R is involved in pain, proinflammatory changes, and blood pressure control. 28209512 8 32 theme lipid 1139:1143 arg1 fraction 1129:1136 the detergent insoluble membrane fraction 1096:1136 the detergent insoluble membrane fraction 1096:1136 WT and the N9Q/N13Q glycosylation-deficient mutant appeared in the detergent insoluble membrane fraction, lipid raft. 28209512 8 32 theme lipid 1139:1143 arg1 raft 1145:1148 lipid raft 1139:1148 lipid raft 1139:1148 WT and the N9Q/N13Q glycosylation-deficient mutant appeared in the detergent insoluble membrane fraction, lipid raft. 28209512 3 33 theme other 379:383 arg1 molecules 395:403 other signaling molecules 379:403 other signaling molecules 379:403 Some GPCRs are localized in lipid rafts for interaction with other signaling molecules. 28209512 6 34 theme Golgi 868:872 arg1 body 874:877 Golgi body 868:877 Golgi body 868:877 Fluorescent microscopy analysis showed that WT, N9Q and N13Q were expressed in the endoplasmic reticulum (ER), Golgi body, and cell membrane, but N9Q/N13Q was only found in the ER. 28209512 3 35 theme signaling 385:393 arg1 molecules 395:403 other signaling molecules 379:403 other signaling molecules 379:403 Some GPCRs are localized in lipid rafts for interaction with other signaling molecules. 28209512 7 36 theme UTP 1016:1018 arg1 stimulation 1020:1030 UTP stimulation 1016:1030 UTP stimulation 1016:1030 WT, N9Q and N13Q moved from the cell surface to endosomes within 15 min after UTP stimulation. 28209512 8 37 theme N9Q/N13Q 1044:1051 arg1 mutant 1077:1082 the N9Q/N13Q glycosylation-deficient mutant 1040:1082 the N9Q/N13Q glycosylation-deficient mutant 1040:1082 WT and the N9Q/N13Q glycosylation-deficient mutant appeared in the detergent insoluble membrane fraction, lipid raft. 28209512 8 38 theme detergent 1100:1108 arg1 fraction 1129:1136 the detergent insoluble membrane fraction 1096:1136 the detergent insoluble membrane fraction 1096:1136 WT and the N9Q/N13Q glycosylation-deficient mutant appeared in the detergent insoluble membrane fraction, lipid raft. 28209512 8 38 theme detergent 1100:1108 arg1 raft 1145:1148 lipid raft 1139:1148 lipid raft 1139:1148 WT and the N9Q/N13Q glycosylation-deficient mutant appeared in the detergent insoluble membrane fraction, lipid raft. 28209512 5 39 theme protein 641:647 arg1 mutants 653:659 mutants 653:659 mutants (N9Q, N13Q, N9Q/N13Q) in COS-7 cells 653:696 Western blotting of the wild type (WT) protein and mutants (N9Q, N13Q, N9Q/N13Q) in COS-7 cells showed that both Asn residues were glycosylated in the WT. 28209512 5 39 theme protein 641:647 arg1 blotting 610:617 Western blotting 602:617 Western blotting of the wild type (WT) protein 602:647 Western blotting of the wild type (WT) protein and mutants (N9Q, N13Q, N9Q/N13Q) in COS-7 cells showed that both Asn residues were glycosylated in the WT. 28209512 5 39 theme protein 641:647 arg1 N9Q/N13Q 673:680 N9Q/N13Q 673:680 N9Q/N13Q 673:680 Western blotting of the wild type (WT) protein and mutants (N9Q, N13Q, N9Q/N13Q) in COS-7 cells showed that both Asn residues were glycosylated in the WT. 28209512 10 40 from increase 1408:1415 arg1 level 1424:1428 the level 1420:1428 the level of N9Q/N13Q 1420:1440 In the presence of epoxomicin, a proteasome inhibitor, there was a significant increase in the level of N9Q/N13Q, which suggests that N-glycan-deficient P2Y2R undergoes proteasomal degradation. 28209512 0 41 theme receptor 55:62 arg1 expression 32:41 N-glycan-dependent cell-surface expression 0:41 N-glycan-dependent cell-surface expression of the P2Y2 receptor 0:62 N-glycan-dependent cell-surface expression of the P2Y2 receptor and N-glycan-independent distribution to lipid rafts. 28209512 0 41 theme receptor 55:62 arg1 distribution 89:100 N-glycan-independent distribution 68:100 N-glycan-independent distribution to lipid rafts 68:115 N-glycan-dependent cell-surface expression of the P2Y2 receptor and N-glycan-independent distribution to lipid rafts. 28209512 10 42 theme proteasome 1362:1371 arg1 epoxomicin 1348:1357 epoxomicin 1348:1357 epoxomicin 1348:1357 In the presence of epoxomicin, a proteasome inhibitor, there was a significant increase in the level of N9Q/N13Q, which suggests that N-glycan-deficient P2Y2R undergoes proteasomal degradation. 28209512 10 42 theme proteasome 1362:1371 arg1 inhibitor 1373:1381 a proteasome inhibitor 1360:1381 a proteasome inhibitor 1360:1381 In the presence of epoxomicin, a proteasome inhibitor, there was a significant increase in the level of N9Q/N13Q, which suggests that N-glycan-deficient P2Y2R undergoes proteasomal degradation. 28209512 10 43 theme significant 1396:1406 arg1 increase 1408:1415 a significant increase 1394:1415 a significant increase 1394:1415 In the presence of epoxomicin, a proteasome inhibitor, there was a significant increase in the level of N9Q/N13Q, which suggests that N-glycan-deficient P2Y2R undergoes proteasomal degradation. 28209512 10 44 theme proteasomal 1498:1508 arg1 degradation 1510:1520 proteasomal degradation 1498:1520 proteasomal degradation 1498:1520 In the presence of epoxomicin, a proteasome inhibitor, there was a significant increase in the level of N9Q/N13Q, which suggests that N-glycan-deficient P2Y2R undergoes proteasomal degradation. 28209512 2 45 theme pressure 300:307 arg1 control 309:315 blood pressure control 294:315 blood pressure control 294:315 P2Y2R is involved in pain, proinflammatory changes, and blood pressure control. 28209512 5 46 from mutants 653:659 arg1 cells 692:696 COS-7 cells 686:696 COS-7 cells 686:696 Western blotting of the wild type (WT) protein and mutants (N9Q, N13Q, N9Q/N13Q) in COS-7 cells showed that both Asn residues were glycosylated in the WT. 28209512 5 47 theme Asn 715:717 arg1 residues 719:726 both Asn residues 710:726 both Asn residues 710:726 Western blotting of the wild type (WT) protein and mutants (N9Q, N13Q, N9Q/N13Q) in COS-7 cells showed that both Asn residues were glycosylated in the WT. 28209512 6 48 theme microscopy 769:778 arg1 analysis 780:787 Fluorescent microscopy analysis 757:787 Fluorescent microscopy analysis 757:787 Fluorescent microscopy analysis showed that WT, N9Q and N13Q were expressed in the endoplasmic reticulum (ER), Golgi body, and cell membrane, but N9Q/N13Q was only found in the ER. 28209512 4 49 with association 572:582 arg1 rafts 595:599 lipid rafts 589:599 lipid rafts 589:599 In this study, we prepared N-glycan-deficient mutants by mutating the two consensus Asn residues for N-glycosylation to Gln to examine intracellular localization and association with lipid rafts. 28209512 2 50 theme blood 294:298 arg1 control 309:315 blood pressure control 294:315 blood pressure control 294:315 P2Y2R is involved in pain, proinflammatory changes, and blood pressure control. 28209512 4 51 theme lipid 589:593 arg1 rafts 595:599 lipid rafts 589:599 lipid rafts 589:599 In this study, we prepared N-glycan-deficient mutants by mutating the two consensus Asn residues for N-glycosylation to Gln to examine intracellular localization and association with lipid rafts. 28209512 6 52 theme Fluorescent 757:767 arg1 microscopy 769:778 Fluorescent microscopy 757:778 Fluorescent microscopy analysis 757:787 Fluorescent microscopy analysis showed that WT, N9Q and N13Q were expressed in the endoplasmic reticulum (ER), Golgi body, and cell membrane, but N9Q/N13Q was only found in the ER. 28209512 5 53 gly glycosylated 733:744 arg1 WT 753:754 the WT 749:754 the WT 749:754 Western blotting of the wild type (WT) protein and mutants (N9Q, N13Q, N9Q/N13Q) in COS-7 cells showed that both Asn residues were glycosylated in the WT. 28209512 5 53 gly glycosylated 733:744 arg1 residues 719:726 both Asn residues 710:726 both Asn residues 710:726 Western blotting of the wild type (WT) protein and mutants (N9Q, N13Q, N9Q/N13Q) in COS-7 cells showed that both Asn residues were glycosylated in the WT. 28209512 5 53 gly glycosylated 733:744 arg2 residues 719:726 both Asn residues 710:726 both Asn residues 710:726 Western blotting of the wild type (WT) protein and mutants (N9Q, N13Q, N9Q/N13Q) in COS-7 cells showed that both Asn residues were glycosylated in the WT. 28209512 9 54 theme cell 1314:1317 arg1 membrane 1319:1326 the cell membrane 1310:1326 the cell membrane 1310:1326 These findings suggest that P2Y2R is localized in lipid rafts in the ER during biosynthesis, and that N-glycosylation is required for subsequent expression in the cell membrane. 28209512 0 55 theme N-glycan-independent 68:87 arg1 distribution 89:100 N-glycan-independent distribution 68:100 N-glycan-independent distribution to lipid rafts 68:115 N-glycan-dependent cell-surface expression of the P2Y2 receptor and N-glycan-independent distribution to lipid rafts. 28209512 3 56 located localized 333:341 arg1 rafts 352:356 lipid rafts 346:356 lipid rafts for interaction with other signaling molecules 346:403 Some GPCRs are localized in lipid rafts for interaction with other signaling molecules. 28209512 3 56 located localized 333:341 arg2 GPCRs 323:327 Some GPCRs 318:327 Some GPCRs 318:327 Some GPCRs are localized in lipid rafts for interaction with other signaling molecules. 28209512 4 57 with localization 555:566 arg1 rafts 595:599 lipid rafts 589:599 lipid rafts 589:599 In this study, we prepared N-glycan-deficient mutants by mutating the two consensus Asn residues for N-glycosylation to Gln to examine intracellular localization and association with lipid rafts. 28209512 1 58 theme G-protein-coupled 145:161 arg1 GPCR 173:176 GPCR 173:176 GPCR 173:176 P2Y2 receptor (P2Y2R) is a G-protein-coupled receptor (GPCR) that couples with Gαq/11 and is stimulated by ATP and UTP. 28209512 1 58 theme G-protein-coupled 145:161 arg1 receptor 163:170 a G-protein-coupled receptor 143:170 a G-protein-coupled receptor (GPCR) that couples with Gαq/11 and is stimulated by ATP and UTP 143:235 P2Y2 receptor (P2Y2R) is a G-protein-coupled receptor (GPCR) that couples with Gαq/11 and is stimulated by ATP and UTP. 28209512 1 58 theme G-protein-coupled 145:161 arg1 receptor 123:130 P2Y2 receptor 118:130 P2Y2 receptor (P2Y2R) 118:138 P2Y2 receptor (P2Y2R) is a G-protein-coupled receptor (GPCR) that couples with Gαq/11 and is stimulated by ATP and UTP. 24530578 8 0 from glycosylation 1353:1365 arg1 α3β1 1370:1373 α3β1 1370:1373 α3β1 1370:1373 Here we show that glycosylation on α3β1 impedes its association with CD151 and modulates spreading and motility of cells apparently to reach an optimum required for invasion of BM. 24530578 3 1 theme invasive 643:650 arg1 cells 659:663 highly invasive B16BL6 cells 636:663 highly invasive B16BL6 cells 636:663 To explore the mechanism and to evaluate the significance of these observations in terms of invasion, highly invasive B16BL6 cells were compared with the parent (B16F10) cells or B16BL6 cells in which glycosylation was inhibited. 24530578 7 2 theme integrin 1283:1290 arg1 function 1292:1299 integrin function 1283:1299 integrin function 1283:1299 Absence of correlation between invasiveness and expression of most tetraspanins (major regulators of integrin function) hints at an alternate mechanism. 24530578 8 3 gly glycosylation 1353:1365 arg1 α3β1 1370:1373 α3β1 1370:1373 α3β1 1370:1373 Here we show that glycosylation on α3β1 impedes its association with CD151 and modulates spreading and motility of cells apparently to reach an optimum required for invasion of BM. 24530578 2 4 theme haptotactic 438:448 arg1 motility 450:457 haptotactic motility 438:457 haptotactic motility on ECM (fibronectin) 438:478 Expression of β1,6 branched N-oligosaccharides associated with invasiveness, has been shown to promote adhesion to most Extra Cellular Matrix (ECM) and basement membrane (BM) components and haptotactic motility on ECM (fibronectin) but attenuate it on BM (laminin/matrigel) components. 24530578 3 5 theme invasion 626:633 arg1 terms 617:621 terms 617:621 terms of invasion 617:633 To explore the mechanism and to evaluate the significance of these observations in terms of invasion, highly invasive B16BL6 cells were compared with the parent (B16F10) cells or B16BL6 cells in which glycosylation was inhibited. 24530578 4 6 theme matrix 806:811 arg1 components 813:822 matrix components 806:822 matrix components 806:822 We demonstrate that increased adhesion to matrix components induced secretion of MMP-9, important for invasion. 24530578 5 7 theme B16BL6 970:975 arg1 cells 977:981 B16BL6 cells 970:981 B16BL6 cells 970:981 Further, both the subunits of integrin receptors for fibronectin (α5β1) and laminin (α3β1) on B16BL6 cells were shown to carry these oligosaccharides. 24530578 7 8 theme most 1244:1247 arg1 tetraspanins 1249:1260 most tetraspanins 1244:1260 most tetraspanins (major regulators of integrin function) 1244:1300 Absence of correlation between invasiveness and expression of most tetraspanins (major regulators of integrin function) hints at an alternate mechanism. 24530578 0 9 theme membrane 168:175 arg1 spreading 110:118 cell spreading 105:118 cell spreading 105:118 Glycosylation of the laminin receptor (α3β1) regulates its association with tetraspanin CD151: Impact on cell spreading, motility, degradation and invasion of basement membrane by tumor cells. 24530578 0 9 theme membrane 168:175 arg1 invasion 147:154 invasion 147:154 invasion 147:154 Glycosylation of the laminin receptor (α3β1) regulates its association with tetraspanin CD151: Impact on cell spreading, motility, degradation and invasion of basement membrane by tumor cells. 24530578 0 9 theme membrane 168:175 arg1 degradation 131:141 degradation 131:141 degradation 131:141 Glycosylation of the laminin receptor (α3β1) regulates its association with tetraspanin CD151: Impact on cell spreading, motility, degradation and invasion of basement membrane by tumor cells. 24530578 0 10 with association 59:69 arg1 CD151 88:92 tetraspanin CD151 76:92 tetraspanin CD151 76:92 Glycosylation of the laminin receptor (α3β1) regulates its association with tetraspanin CD151: Impact on cell spreading, motility, degradation and invasion of basement membrane by tumor cells. 24530578 6 11 theme surface 1087:1093 arg1 expression 1095:1104 their surface expression 1081:1104 their surface expression 1081:1104 Although, glycosylation of receptors had no effect on their surface expression, it had same differential effect on cell spreading as haptotactic motility. 24530578 2 12 theme branched 267:274 arg1 N-oligosaccharides 276:293 β1,6 branched N-oligosaccharides 262:293 β1,6 branched N-oligosaccharides associated with invasiveness 262:322 Expression of β1,6 branched N-oligosaccharides associated with invasiveness, has been shown to promote adhesion to most Extra Cellular Matrix (ECM) and basement membrane (BM) components and haptotactic motility on ECM (fibronectin) but attenuate it on BM (laminin/matrigel) components. 24530578 1 13 theme cancer 229:234 arg1 metastasis 236:245 cancer metastasis 229:245 cancer metastasis 229:245 Invasion is the key requirement for cancer metastasis. 24530578 0 14 theme tetraspanin 76:86 arg1 CD151 88:92 tetraspanin CD151 76:92 tetraspanin CD151 76:92 Glycosylation of the laminin receptor (α3β1) regulates its association with tetraspanin CD151: Impact on cell spreading, motility, degradation and invasion of basement membrane by tumor cells. 24530578 0 15 theme basement 159:166 arg1 membrane 168:175 basement membrane 159:175 basement membrane 159:175 Glycosylation of the laminin receptor (α3β1) regulates its association with tetraspanin CD151: Impact on cell spreading, motility, degradation and invasion of basement membrane by tumor cells. 24530578 5 16 contain carry 997:1001 arg1 subunits 894:901 both the subunits 885:901 both the subunits of integrin receptors for fibronectin (α5β1) and laminin (α3β1) on B16BL6 cells 885:981 Further, both the subunits of integrin receptors for fibronectin (α5β1) and laminin (α3β1) on B16BL6 cells were shown to carry these oligosaccharides. 24530578 5 16 contain carry 997:1001 arg2 oligosaccharides 1009:1024 these oligosaccharides 1003:1024 these oligosaccharides 1003:1024 Further, both the subunits of integrin receptors for fibronectin (α5β1) and laminin (α3β1) on B16BL6 cells were shown to carry these oligosaccharides. 24530578 0 17 theme tumor 180:184 arg1 cells 186:190 tumor cells 180:190 tumor cells 180:190 Glycosylation of the laminin receptor (α3β1) regulates its association with tetraspanin CD151: Impact on cell spreading, motility, degradation and invasion of basement membrane by tumor cells. 24530578 2 18 theme Cellular 374:381 arg1 ECM 391:393 ECM 391:393 ECM 391:393 Expression of β1,6 branched N-oligosaccharides associated with invasiveness, has been shown to promote adhesion to most Extra Cellular Matrix (ECM) and basement membrane (BM) components and haptotactic motility on ECM (fibronectin) but attenuate it on BM (laminin/matrigel) components. 24530578 2 18 theme Cellular 374:381 arg1 Matrix 383:388 most Extra Cellular Matrix 363:388 most Extra Cellular Matrix (ECM) 363:394 Expression of β1,6 branched N-oligosaccharides associated with invasiveness, has been shown to promote adhesion to most Extra Cellular Matrix (ECM) and basement membrane (BM) components and haptotactic motility on ECM (fibronectin) but attenuate it on BM (laminin/matrigel) components. 24530578 5 19 from cells 977:981 arg1 subunits 894:901 both the subunits 885:901 both the subunits of integrin receptors for fibronectin (α5β1) and laminin (α3β1) on B16BL6 cells 885:981 Further, both the subunits of integrin receptors for fibronectin (α5β1) and laminin (α3β1) on B16BL6 cells were shown to carry these oligosaccharides. 24530578 3 20 theme B16BL6 652:657 arg1 cells 659:663 highly invasive B16BL6 cells 636:663 highly invasive B16BL6 cells 636:663 To explore the mechanism and to evaluate the significance of these observations in terms of invasion, highly invasive B16BL6 cells were compared with the parent (B16F10) cells or B16BL6 cells in which glycosylation was inhibited. 24530578 6 21 gly glycosylation 1037:1049 arg1 receptors 1054:1062 receptors 1054:1062 receptors 1054:1062 Although, glycosylation of receptors had no effect on their surface expression, it had same differential effect on cell spreading as haptotactic motility. 24530578 5 22 theme integrin 906:913 arg1 receptors 915:923 integrin receptors 906:923 integrin receptors for fibronectin (α5β1) and laminin (α3β1) on B16BL6 cells 906:981 Further, both the subunits of integrin receptors for fibronectin (α5β1) and laminin (α3β1) on B16BL6 cells were shown to carry these oligosaccharides. 24530578 5 23 from receptors 915:923 arg1 cells 977:981 B16BL6 cells 970:981 B16BL6 cells 970:981 Further, both the subunits of integrin receptors for fibronectin (α5β1) and laminin (α3β1) on B16BL6 cells were shown to carry these oligosaccharides. 24530578 2 24 theme Extra 368:372 arg1 ECM 391:393 ECM 391:393 ECM 391:393 Expression of β1,6 branched N-oligosaccharides associated with invasiveness, has been shown to promote adhesion to most Extra Cellular Matrix (ECM) and basement membrane (BM) components and haptotactic motility on ECM (fibronectin) but attenuate it on BM (laminin/matrigel) components. 24530578 2 24 theme Extra 368:372 arg1 Matrix 383:388 most Extra Cellular Matrix 363:388 most Extra Cellular Matrix (ECM) 363:394 Expression of β1,6 branched N-oligosaccharides associated with invasiveness, has been shown to promote adhesion to most Extra Cellular Matrix (ECM) and basement membrane (BM) components and haptotactic motility on ECM (fibronectin) but attenuate it on BM (laminin/matrigel) components. 24530578 7 25 dep tetraspanins 1249:1260 arg1 regulators 1269:1278 major regulators 1263:1278 major regulators of integrin function 1263:1299 Absence of correlation between invasiveness and expression of most tetraspanins (major regulators of integrin function) hints at an alternate mechanism. 24530578 4 26 theme increased 784:792 arg1 adhesion 794:801 increased adhesion 784:801 increased adhesion to matrix components 784:822 We demonstrate that increased adhesion to matrix components induced secretion of MMP-9, important for invasion. 24530578 7 27 theme alternate 1314:1322 arg1 mechanism 1324:1332 an alternate mechanism 1311:1332 an alternate mechanism 1311:1332 Absence of correlation between invasiveness and expression of most tetraspanins (major regulators of integrin function) hints at an alternate mechanism. 24530578 3 28 theme parent 688:693 arg1 cells 704:708 the parent (B16F10) cells 684:708 the parent (B16F10) cells 684:708 To explore the mechanism and to evaluate the significance of these observations in terms of invasion, highly invasive B16BL6 cells were compared with the parent (B16F10) cells or B16BL6 cells in which glycosylation was inhibited. 24530578 6 29 theme cell 1142:1145 arg1 spreading 1147:1155 cell spreading 1142:1155 cell spreading as haptotactic motility 1142:1179 Although, glycosylation of receptors had no effect on their surface expression, it had same differential effect on cell spreading as haptotactic motility. 24530578 2 30 from adhesion 351:358 arg1 fibronectin 467:477 ECM (fibronectin) 462:478 ECM (fibronectin) 462:478 Expression of β1,6 branched N-oligosaccharides associated with invasiveness, has been shown to promote adhesion to most Extra Cellular Matrix (ECM) and basement membrane (BM) components and haptotactic motility on ECM (fibronectin) but attenuate it on BM (laminin/matrigel) components. 24530578 6 31 theme haptotactic 1160:1170 arg1 motility 1172:1179 haptotactic motility 1160:1179 haptotactic motility 1160:1179 Although, glycosylation of receptors had no effect on their surface expression, it had same differential effect on cell spreading as haptotactic motility. 24530578 0 32 theme laminin 21:27 arg1 α3β1 39:42 α3β1 39:42 α3β1 39:42 Glycosylation of the laminin receptor (α3β1) regulates its association with tetraspanin CD151: Impact on cell spreading, motility, degradation and invasion of basement membrane by tumor cells. 24530578 0 32 theme laminin 21:27 arg1 receptor 29:36 laminin receptor 21:36 the laminin receptor (α3β1) 17:43 Glycosylation of the laminin receptor (α3β1) regulates its association with tetraspanin CD151: Impact on cell spreading, motility, degradation and invasion of basement membrane by tumor cells. 24530578 0 33 theme cell 105:108 arg1 spreading 110:118 cell spreading 105:118 cell spreading 105:118 Glycosylation of the laminin receptor (α3β1) regulates its association with tetraspanin CD151: Impact on cell spreading, motility, degradation and invasion of basement membrane by tumor cells. 24530578 0 33 theme cell 105:108 arg1 invasion 147:154 invasion 147:154 invasion 147:154 Glycosylation of the laminin receptor (α3β1) regulates its association with tetraspanin CD151: Impact on cell spreading, motility, degradation and invasion of basement membrane by tumor cells. 24530578 0 33 theme cell 105:108 arg1 degradation 131:141 degradation 131:141 degradation 131:141 Glycosylation of the laminin receptor (α3β1) regulates its association with tetraspanin CD151: Impact on cell spreading, motility, degradation and invasion of basement membrane by tumor cells. 24530578 0 33 theme cell 105:108 arg1 motility 121:128 motility 121:128 motility 121:128 Glycosylation of the laminin receptor (α3β1) regulates its association with tetraspanin CD151: Impact on cell spreading, motility, degradation and invasion of basement membrane by tumor cells. 24530578 7 34 theme function 1292:1299 arg1 regulators 1269:1278 major regulators 1263:1278 major regulators of integrin function 1263:1299 Absence of correlation between invasiveness and expression of most tetraspanins (major regulators of integrin function) hints at an alternate mechanism. 24530578 2 35 theme N-oligosaccharides 276:293 arg1 Expression 248:257 Expression 248:257 Expression 248:257 Expression of β1,6 branched N-oligosaccharides associated with invasiveness, has been shown to promote adhesion to most Extra Cellular Matrix (ECM) and basement membrane (BM) components and haptotactic motility on ECM (fibronectin) but attenuate it on BM (laminin/matrigel) components. 24530578 2 36 from motility 450:457 arg1 fibronectin 467:477 ECM (fibronectin) 462:478 ECM (fibronectin) 462:478 Expression of β1,6 branched N-oligosaccharides associated with invasiveness, has been shown to promote adhesion to most Extra Cellular Matrix (ECM) and basement membrane (BM) components and haptotactic motility on ECM (fibronectin) but attenuate it on BM (laminin/matrigel) components. 24530578 0 37 dep regulates 45:53 arg1 Impact 95:100 Impact 95:100 Impact on cell spreading, motility, degradation and invasion of basement membrane by tumor cells 95:190 Glycosylation of the laminin receptor (α3β1) regulates its association with tetraspanin CD151: Impact on cell spreading, motility, degradation and invasion of basement membrane by tumor cells. 24530578 5 38 from subunits 894:901 arg1 cells 977:981 B16BL6 cells 970:981 B16BL6 cells 970:981 Further, both the subunits of integrin receptors for fibronectin (α5β1) and laminin (α3β1) on B16BL6 cells were shown to carry these oligosaccharides. 24530578 0 39 gly Glycosylation 0:12 arg1 α3β1 39:42 α3β1 39:42 α3β1 39:42 Glycosylation of the laminin receptor (α3β1) regulates its association with tetraspanin CD151: Impact on cell spreading, motility, degradation and invasion of basement membrane by tumor cells. 24530578 0 39 gly Glycosylation 0:12 arg1 receptor 29:36 laminin receptor 21:36 the laminin receptor (α3β1) 17:43 Glycosylation of the laminin receptor (α3β1) regulates its association with tetraspanin CD151: Impact on cell spreading, motility, degradation and invasion of basement membrane by tumor cells. 24530578 7 40 theme correlation 1193:1203 arg1 Absence 1182:1188 Absence 1182:1188 Absence of correlation between invasiveness and expression of most tetraspanins (major regulators of integrin function) 1182:1300 Absence of correlation between invasiveness and expression of most tetraspanins (major regulators of integrin function) hints at an alternate mechanism. 24530578 0 41 theme receptor 29:36 arg1 Glycosylation 0:12 Glycosylation 0:12 Glycosylation of the laminin receptor (α3β1) 0:43 Glycosylation of the laminin receptor (α3β1) regulates its association with tetraspanin CD151: Impact on cell spreading, motility, degradation and invasion of basement membrane by tumor cells. 24530578 2 42 theme basement 400:407 arg1 membrane 409:416 basement membrane 400:416 basement membrane (BM) 400:421 Expression of β1,6 branched N-oligosaccharides associated with invasiveness, has been shown to promote adhesion to most Extra Cellular Matrix (ECM) and basement membrane (BM) components and haptotactic motility on ECM (fibronectin) but attenuate it on BM (laminin/matrigel) components. 24530578 2 42 theme basement 400:407 arg1 BM 419:420 BM 419:420 BM 419:420 Expression of β1,6 branched N-oligosaccharides associated with invasiveness, has been shown to promote adhesion to most Extra Cellular Matrix (ECM) and basement membrane (BM) components and haptotactic motility on ECM (fibronectin) but attenuate it on BM (laminin/matrigel) components. 24530578 3 43 gly glycosylation 735:747 arg1 cells 704:708 the parent (B16F10) cells 684:708 the parent (B16F10) cells 684:708 To explore the mechanism and to evaluate the significance of these observations in terms of invasion, highly invasive B16BL6 cells were compared with the parent (B16F10) cells or B16BL6 cells in which glycosylation was inhibited. 24530578 3 43 gly glycosylation 735:747 arg1 cells 720:724 B16BL6 cells 713:724 B16BL6 cells 713:724 To explore the mechanism and to evaluate the significance of these observations in terms of invasion, highly invasive B16BL6 cells were compared with the parent (B16F10) cells or B16BL6 cells in which glycosylation was inhibited. 24530578 6 44 theme differential 1119:1130 arg1 effect 1132:1137 same differential effect 1114:1137 same differential effect 1114:1137 Although, glycosylation of receptors had no effect on their surface expression, it had same differential effect on cell spreading as haptotactic motility. 24530578 4 45 theme MMP-9 845:849 arg1 secretion 832:840 secretion 832:840 secretion 832:840 We demonstrate that increased adhesion to matrix components induced secretion of MMP-9, important for invasion. 24530578 8 46 theme cells 1450:1454 arg1 motility 1438:1445 motility 1438:1445 motility 1438:1445 Here we show that glycosylation on α3β1 impedes its association with CD151 and modulates spreading and motility of cells apparently to reach an optimum required for invasion of BM. 24530578 8 46 theme cells 1450:1454 arg1 spreading 1424:1432 spreading 1424:1432 spreading 1424:1432 Here we show that glycosylation on α3β1 impedes its association with CD151 and modulates spreading and motility of cells apparently to reach an optimum required for invasion of BM. 24530578 3 47 theme B16F10 696:701 arg1 cells 704:708 the parent (B16F10) cells 684:708 the parent (B16F10) cells 684:708 To explore the mechanism and to evaluate the significance of these observations in terms of invasion, highly invasive B16BL6 cells were compared with the parent (B16F10) cells or B16BL6 cells in which glycosylation was inhibited. 24530578 2 48 theme BM 500:501 arg1 components 522:531 BM (laminin/matrigel) components 500:531 BM (laminin/matrigel) components 500:531 Expression of β1,6 branched N-oligosaccharides associated with invasiveness, has been shown to promote adhesion to most Extra Cellular Matrix (ECM) and basement membrane (BM) components and haptotactic motility on ECM (fibronectin) but attenuate it on BM (laminin/matrigel) components. 24530578 0 49 from Impact 95:100 arg1 spreading 110:118 cell spreading 105:118 cell spreading 105:118 Glycosylation of the laminin receptor (α3β1) regulates its association with tetraspanin CD151: Impact on cell spreading, motility, degradation and invasion of basement membrane by tumor cells. 24530578 0 49 from Impact 95:100 arg1 invasion 147:154 invasion 147:154 invasion 147:154 Glycosylation of the laminin receptor (α3β1) regulates its association with tetraspanin CD151: Impact on cell spreading, motility, degradation and invasion of basement membrane by tumor cells. 24530578 0 49 from Impact 95:100 arg1 degradation 131:141 degradation 131:141 degradation 131:141 Glycosylation of the laminin receptor (α3β1) regulates its association with tetraspanin CD151: Impact on cell spreading, motility, degradation and invasion of basement membrane by tumor cells. 24530578 0 49 from Impact 95:100 arg1 motility 121:128 motility 121:128 motility 121:128 Glycosylation of the laminin receptor (α3β1) regulates its association with tetraspanin CD151: Impact on cell spreading, motility, degradation and invasion of basement membrane by tumor cells. 24530578 6 50 theme same 1114:1117 arg1 effect 1132:1137 same differential effect 1114:1137 same differential effect 1114:1137 Although, glycosylation of receptors had no effect on their surface expression, it had same differential effect on cell spreading as haptotactic motility. 24530578 9 51 theme cancer 1573:1578 arg1 cells 1580:1584 cancer cells 1573:1584 cancer cells 1573:1584 These studies demonstrate the complex mechanisms used by cancer cells to be invasive. 24530578 6 52 contain had 1110:1112 arg1 it 1107:1108 it 1107:1108 it 1107:1108 Although, glycosylation of receptors had no effect on their surface expression, it had same differential effect on cell spreading as haptotactic motility. 24530578 6 52 contain had 1110:1112 arg2 effect 1132:1137 same differential effect 1114:1137 same differential effect 1114:1137 Although, glycosylation of receptors had no effect on their surface expression, it had same differential effect on cell spreading as haptotactic motility. 24530578 2 53 theme laminin/matrigel 504:519 arg1 components 522:531 BM (laminin/matrigel) components 500:531 BM (laminin/matrigel) components 500:531 Expression of β1,6 branched N-oligosaccharides associated with invasiveness, has been shown to promote adhesion to most Extra Cellular Matrix (ECM) and basement membrane (BM) components and haptotactic motility on ECM (fibronectin) but attenuate it on BM (laminin/matrigel) components. 24530578 5 54 theme receptors 915:923 arg1 subunits 894:901 both the subunits 885:901 both the subunits of integrin receptors for fibronectin (α5β1) and laminin (α3β1) on B16BL6 cells 885:981 Further, both the subunits of integrin receptors for fibronectin (α5β1) and laminin (α3β1) on B16BL6 cells were shown to carry these oligosaccharides. 24530578 2 55 dep Matrix 383:388 arg1 components 423:432 components 423:432 components 423:432 Expression of β1,6 branched N-oligosaccharides associated with invasiveness, has been shown to promote adhesion to most Extra Cellular Matrix (ECM) and basement membrane (BM) components and haptotactic motility on ECM (fibronectin) but attenuate it on BM (laminin/matrigel) components. 24530578 6 56 theme receptors 1054:1062 arg1 glycosylation 1037:1049 glycosylation 1037:1049 glycosylation of receptors 1037:1062 Although, glycosylation of receptors had no effect on their surface expression, it had same differential effect on cell spreading as haptotactic motility. 24530578 8 57 theme BM 1512:1513 arg1 invasion 1500:1507 invasion 1500:1507 invasion of BM 1500:1513 Here we show that glycosylation on α3β1 impedes its association with CD151 and modulates spreading and motility of cells apparently to reach an optimum required for invasion of BM. 24530578 3 58 theme observations 601:612 arg1 significance 579:590 the significance 575:590 the significance of these observations in terms of invasion 575:633 To explore the mechanism and to evaluate the significance of these observations in terms of invasion, highly invasive B16BL6 cells were compared with the parent (B16F10) cells or B16BL6 cells in which glycosylation was inhibited. 24530578 9 59 theme complex 1546:1552 arg1 mechanisms 1554:1563 the complex mechanisms 1542:1563 the complex mechanisms used by cancer cells to be invasive 1542:1599 These studies demonstrate the complex mechanisms used by cancer cells to be invasive. 24530578 2 60 theme ECM 462:464 arg1 fibronectin 467:477 ECM (fibronectin) 462:478 ECM (fibronectin) 462:478 Expression of β1,6 branched N-oligosaccharides associated with invasiveness, has been shown to promote adhesion to most Extra Cellular Matrix (ECM) and basement membrane (BM) components and haptotactic motility on ECM (fibronectin) but attenuate it on BM (laminin/matrigel) components. 24530578 4 61 theme important 852:860 arg1 secretion 832:840 secretion 832:840 secretion 832:840 We demonstrate that increased adhesion to matrix components induced secretion of MMP-9, important for invasion. 24530578 7 62 theme tetraspanins 1249:1260 arg1 invasiveness 1213:1224 invasiveness 1213:1224 invasiveness 1213:1224 Absence of correlation between invasiveness and expression of most tetraspanins (major regulators of integrin function) hints at an alternate mechanism. 24530578 7 62 theme tetraspanins 1249:1260 arg1 expression 1230:1239 expression 1230:1239 expression of most tetraspanins (major regulators of integrin function) 1230:1300 Absence of correlation between invasiveness and expression of most tetraspanins (major regulators of integrin function) hints at an alternate mechanism. 24530578 3 63 theme B16BL6 713:718 arg1 cells 720:724 B16BL6 cells 713:724 B16BL6 cells 713:724 To explore the mechanism and to evaluate the significance of these observations in terms of invasion, highly invasive B16BL6 cells were compared with the parent (B16F10) cells or B16BL6 cells in which glycosylation was inhibited. 24530578 6 64 contain had 1064:1066 arg2 effect 1071:1076 no effect 1068:1076 no effect 1068:1076 Although, glycosylation of receptors had no effect on their surface expression, it had same differential effect on cell spreading as haptotactic motility. 24530578 6 64 contain had 1064:1066 arg1 glycosylation 1037:1049 glycosylation 1037:1049 glycosylation of receptors 1037:1062 Although, glycosylation of receptors had no effect on their surface expression, it had same differential effect on cell spreading as haptotactic motility. 24530578 7 65 theme major 1263:1267 arg1 regulators 1269:1278 major regulators 1263:1278 major regulators of integrin function 1263:1299 Absence of correlation between invasiveness and expression of most tetraspanins (major regulators of integrin function) hints at an alternate mechanism. 24530578 3 66 from significance 579:590 arg1 terms 617:621 terms 617:621 terms of invasion 617:633 To explore the mechanism and to evaluate the significance of these observations in terms of invasion, highly invasive B16BL6 cells were compared with the parent (B16F10) cells or B16BL6 cells in which glycosylation was inhibited. 24530578 8 67 with association 1387:1397 arg1 CD151 1404:1408 CD151 1404:1408 CD151 1404:1408 Here we show that glycosylation on α3β1 impedes its association with CD151 and modulates spreading and motility of cells apparently to reach an optimum required for invasion of BM. 24530578 1 68 theme key 209:211 arg1 Invasion 193:200 Invasion 193:200 Invasion 193:200 Invasion is the key requirement for cancer metastasis. 24530578 1 68 theme key 209:211 arg1 requirement 213:223 the key requirement 205:223 the key requirement for cancer metastasis 205:245 Invasion is the key requirement for cancer metastasis. 26486590 2 0 attach isolated 98:105 arg2 acidobacteria 84:96 acidobacteria 84:96 acidobacteria isolated from Namibian soils 84:125 nov., acidobacteria isolated from Namibian soils, and emended description of the family Acidobacteriaceae. 26486590 2 0 attach isolated 98:105 arg1 soils 121:125 Namibian soils 112:125 Namibian soils 112:125 nov., acidobacteria isolated from Namibian soils, and emended description of the family Acidobacteriaceae. 26486590 12 1 theme strain 1396:1401 arg1 A2-1cT 1403:1408 strain A2-1cT 1396:1408 strain A2-1cT 1396:1408 The major quinone in all three strains was MK-8; MK-7 occurred in strain A2-1cT as a minor compound. 26486590 4 2 theme rRNA 366:369 arg1 analyses 385:392 16S rRNA gene sequence analyses 362:392 16S rRNA gene sequence analyses 362:392 16S rRNA gene sequence analyses placed them within subdivision 1 of the Acidobacteria and revealed 100 % similarity between strains 277T and 307 and 98.2 % similarity between A2-1cT and the former two strains. 26486590 9 3 theme broad 1132:1136 arg1 range 1150:1154 a broad temperature range 1130:1154 a broad temperature range for growth and a moderately acidic pH optimum 1130:1200 All three strains were aerobic, chemoheterotrophic mesophiles with a broad temperature range for growth and a moderately acidic pH optimum. 26486590 4 4 theme sequence 376:383 arg1 analyses 385:392 16S rRNA gene sequence analyses 362:392 16S rRNA gene sequence analyses 362:392 16S rRNA gene sequence analyses placed them within subdivision 1 of the Acidobacteria and revealed 100 % similarity between strains 277T and 307 and 98.2 % similarity between A2-1cT and the former two strains. 26486590 5 5 theme published 607:615 arg1 names 617:621 validly published names 599:621 validly published names 599:621 The closest relatives with validly published names were Telmatobacter bradus, Acidicapsa borealis and Acidicapsa ligni (94.7-95.9 % similarity to the type strains). 26486590 16 6 theme genus 1740:1744 arg1 nov. 1767:1770 the novel genus Occallatibacter gen. nov. 1730:1770 the novel genus Occallatibacter gen. nov. 1730:1770 Based on these characteristics, the three isolates are assigned to two novel species of the novel genus Occallatibacter gen. nov., Occallatibacter riparius sp. 26486590 16 6 theme genus 1740:1744 arg1 sp 1798:1799 Occallatibacter riparius sp 1773:1799 Occallatibacter riparius sp 1773:1799 Based on these characteristics, the three isolates are assigned to two novel species of the novel genus Occallatibacter gen. nov., Occallatibacter riparius sp. 26486590 8 7 theme strains 940:946 arg1 Colonies 928:935 Colonies 928:935 Colonies of strains 277T and 307 928:959 Colonies of strains 277T and 307 were white to cream and light pink, respectively, while strain A2-1cT displayed a bright pink colour. 26486590 19 8 theme described 2033:2041 arg1 taxa 2043:2046 several other recently described taxa 2010:2046 several other recently described taxa 2010:2046 Together with several other recently described taxa, the novel isolates provide the basis for an emended description of the established family Acidobacteriaceae. 26486590 16 9 theme gen. 1762:1765 arg1 nov. 1767:1770 the novel genus Occallatibacter gen. nov. 1730:1770 the novel genus Occallatibacter gen. nov. 1730:1770 Based on these characteristics, the three isolates are assigned to two novel species of the novel genus Occallatibacter gen. nov., Occallatibacter riparius sp. 26486590 16 9 theme gen. 1762:1765 arg1 sp 1798:1799 Occallatibacter riparius sp 1773:1799 Occallatibacter riparius sp 1773:1799 Based on these characteristics, the three isolates are assigned to two novel species of the novel genus Occallatibacter gen. nov., Occallatibacter riparius sp. 26486590 17 10 theme [type 1807:1811 arg1 25169 = LMG 1887:1897  = DSM 25169 = LMG 26947 1880:1903  = DSM 25169 = LMG 26947 1880:1903 nov. [type strain 277T ( = DSM 25168T = LMG 26948T) and reference strain 307 ( = DSM 25169 = LMG 26947)] and Occallatibacter savannae sp. 26486590 17 10 theme [type 1807:1811 arg1 strain 1813:1818 nov. [type strain 277T 1802:1823 nov. [type strain 277T ( = DSM 25168T = LMG 26948T) 1802:1852 nov. [type strain 277T ( = DSM 25168T = LMG 26948T) and reference strain 307 ( = DSM 25169 = LMG 26947)] and Occallatibacter savannae sp. 26486590 17 10 theme [type 1807:1811 arg1 26948T 1846:1851  = DSM 25168T = LMG 26948T 1826:1851  = DSM 25168T = LMG 26948T 1826:1851 nov. [type strain 277T ( = DSM 25168T = LMG 26948T) and reference strain 307 ( = DSM 25169 = LMG 26947)] and Occallatibacter savannae sp. 26486590 17 11 theme  = DSM 1880:1885 arg1 25169 = LMG 1887:1897  = DSM 25169 = LMG 26947 1880:1903  = DSM 25169 = LMG 26947 1880:1903 nov. [type strain 277T ( = DSM 25168T = LMG 26948T) and reference strain 307 ( = DSM 25169 = LMG 26947)] and Occallatibacter savannae sp. 26486590 17 11 theme  = DSM 1880:1885 arg1 strain 1813:1818 nov. [type strain 277T 1802:1823 nov. [type strain 277T ( = DSM 25168T = LMG 26948T) 1802:1852 nov. [type strain 277T ( = DSM 25168T = LMG 26948T) and reference strain 307 ( = DSM 25169 = LMG 26947)] and Occallatibacter savannae sp. 26486590 3 12 theme Namibian 268:275 arg1 soil 288:291 a Namibian river-bank soil 266:291 a Namibian river-bank soil (strains 277T and 307) 266:314 Three Gram-negative, non-spore-forming, encapsulated bacteria were isolated from a Namibian river-bank soil (strains 277T and 307) and a semiarid savannah soil (strain A2-1cT). 26486590 3 12 theme Namibian 268:275 arg1 strains 294:300 strains 277T and 307 294:313 strains 277T and 307 294:313 Three Gram-negative, non-spore-forming, encapsulated bacteria were isolated from a Namibian river-bank soil (strains 277T and 307) and a semiarid savannah soil (strain A2-1cT). 26486590 5 13 theme 94.7-95.9  692:701 arg1 % 702:702 % 702:702 % 702:702 The closest relatives with validly published names were Telmatobacter bradus, Acidicapsa borealis and Acidicapsa ligni (94.7-95.9 % similarity to the type strains). 26486590 9 14 theme acidic 1184:1189 arg1 optimum 1194:1200 a moderately acidic pH optimum 1171:1200 a moderately acidic pH optimum 1171:1200 All three strains were aerobic, chemoheterotrophic mesophiles with a broad temperature range for growth and a moderately acidic pH optimum. 26486590 19 15 theme novel 2053:2057 arg1 isolates 2059:2066 the novel isolates 2049:2066 the novel isolates 2049:2066 Together with several other recently described taxa, the novel isolates provide the basis for an emended description of the established family Acidobacteriaceae. 26486590 19 16 theme emended 2093:2099 arg1 description 2101:2111 an emended description 2090:2111 an emended description of the established family Acidobacteriaceae 2090:2155 Together with several other recently described taxa, the novel isolates provide the basis for an emended description of the established family Acidobacteriaceae. 26486590 18 17 theme  = DSM 1966:1971 arg1 26946T 1986:1991  = DSM 25170T = LMG 26946T 1966:1991  = DSM 25170T = LMG 26946T 1966:1991 nov. [type strain A2-1cT ( = DSM 25170T = LMG 26946T)]. 26486590 18 17 theme  = DSM 1966:1971 arg1 A2-1cT 1958:1963 nov. [type strain A2-1cT 1940:1963 nov. [type strain A2-1cT ( = DSM 25170T = LMG 26946T) 1940:1992 nov. [type strain A2-1cT ( = DSM 25170T = LMG 26946T)]. 26486590 19 18 theme established 2120:2130 arg1 Acidobacteriaceae 2139:2155 the established family Acidobacteriaceae 2116:2155 the established family Acidobacteriaceae 2116:2155 Together with several other recently described taxa, the novel isolates provide the basis for an emended description of the established family Acidobacteriaceae. 26486590 7 19 theme periplasmic 909:919 arg1 space 921:925 a thick periplasmic space 901:925 a thick periplasmic space 901:925 Ultrastructural analyses revealed a thick cell envelope, resulting mainly from a thick periplasmic space. 26486590 8 20 dep strains 940:946 arg1 277T 948:951 277T 948:951 277T 948:951 Colonies of strains 277T and 307 were white to cream and light pink, respectively, while strain A2-1cT displayed a bright pink colour. 26486590 8 20 dep strains 940:946 arg1 307 957:959 307 957:959 307 957:959 Colonies of strains 277T and 307 were white to cream and light pink, respectively, while strain A2-1cT displayed a bright pink colour. 26486590 3 21 theme savannah 331:338 arg1 soil 340:343 a semiarid savannah soil 320:343 a semiarid savannah soil (strain A2-1cT) 320:359 Three Gram-negative, non-spore-forming, encapsulated bacteria were isolated from a Namibian river-bank soil (strains 277T and 307) and a semiarid savannah soil (strain A2-1cT). 26486590 3 21 theme savannah 331:338 arg1 A2-1cT 353:358 strain A2-1cT 346:358 strain A2-1cT 346:358 Three Gram-negative, non-spore-forming, encapsulated bacteria were isolated from a Namibian river-bank soil (strains 277T and 307) and a semiarid savannah soil (strain A2-1cT). 26486590 4 22 dep similarity 518:527 arg1 % 516:516 % 516:516 % 516:516 16S rRNA gene sequence analyses placed them within subdivision 1 of the Acidobacteria and revealed 100 % similarity between strains 277T and 307 and 98.2 % similarity between A2-1cT and the former two strains. 26486590 5 23 dep Telmatobacter 628:640 arg1 similarity 704:713 94.7-95.9 % similarity 692:713 94.7-95.9 % similarity to the type strains 692:733 The closest relatives with validly published names were Telmatobacter bradus, Acidicapsa borealis and Acidicapsa ligni (94.7-95.9 % similarity to the type strains). 26486590 5 23 dep Telmatobacter 628:640 arg1 bradus 642:647 Telmatobacter bradus 628:647 Telmatobacter bradus 628:647 The closest relatives with validly published names were Telmatobacter bradus, Acidicapsa borealis and Acidicapsa ligni (94.7-95.9 % similarity to the type strains). 26486590 4 24 theme 100  461:464 arg1 % 465:465 % 465:465 % 465:465 16S rRNA gene sequence analyses placed them within subdivision 1 of the Acidobacteria and revealed 100 % similarity between strains 277T and 307 and 98.2 % similarity between A2-1cT and the former two strains. 26486590 10 25 theme complex 1214:1220 arg1 substrates 1236:1245 complex proteinaceous substrates 1214:1245 complex proteinaceous substrates 1214:1245 Sugars and complex proteinaceous substrates were the preferred carbon and energy sources. 26486590 10 25 theme complex 1214:1220 arg1 Sugars 1203:1208 Sugars 1203:1208 Sugars 1203:1208 Sugars and complex proteinaceous substrates were the preferred carbon and energy sources. 26486590 10 25 theme complex 1214:1220 arg1 carbon 1266:1271 the preferred carbon and energy sources 1252:1290 carbon 1266:1271 Sugars and complex proteinaceous substrates were the preferred carbon and energy sources. 26486590 13 26 theme fatty 1437:1441 arg1 acids 1443:1447 Major fatty acids 1431:1447 Major fatty acids 1431:1447 Major fatty acids were iso-C15 : 0 and iso-C17 : 1ω7c. 26486590 0 27 theme Occallatibacter 0:14 arg1 nov. 30:33 Occallatibacter riparius gen. nov. 0:33 Occallatibacter riparius gen. nov. 0:33 Occallatibacter riparius gen. nov., sp. 26486590 19 28 theme Acidobacteriaceae 2139:2155 arg1 description 2101:2111 an emended description 2090:2111 an emended description of the established family Acidobacteriaceae 2090:2155 Together with several other recently described taxa, the novel isolates provide the basis for an emended description of the established family Acidobacteriaceae. 26486590 12 29 from quinone 1340:1346 arg1 strains 1361:1367 all three strains 1351:1367 all three strains 1351:1367 The major quinone in all three strains was MK-8; MK-7 occurred in strain A2-1cT as a minor compound. 26486590 6 30 theme strains 756:762 arg1 Cells 737:741 Cells 737:741 Cells of all three strains 737:762 Cells of all three strains were rod-shaped and motile and divided by binary fission. 26486590 0 31 theme gen. 25:28 arg1 nov. 30:33 Occallatibacter riparius gen. nov. 0:33 Occallatibacter riparius gen. nov. 0:33 Occallatibacter riparius gen. nov., sp. 26486590 8 32 theme strain 1017:1022 arg1 A2-1cT 1024:1029 strain A2-1cT 1017:1029 strain A2-1cT 1017:1029 Colonies of strains 277T and 307 were white to cream and light pink, respectively, while strain A2-1cT displayed a bright pink colour. 26486590 18 33 theme nov. 1940:1943 arg1 26946T 1986:1991  = DSM 25170T = LMG 26946T 1966:1991  = DSM 25170T = LMG 26946T 1966:1991 nov. [type strain A2-1cT ( = DSM 25170T = LMG 26946T)]. 26486590 18 33 theme nov. 1940:1943 arg1 A2-1cT 1958:1963 nov. [type strain A2-1cT 1940:1963 nov. [type strain A2-1cT ( = DSM 25170T = LMG 26946T) 1940:1992 nov. [type strain A2-1cT ( = DSM 25170T = LMG 26946T)]. 26486590 9 34 dep aerobic 1086:1092 arg1 chemoheterotrophic 1095:1112 chemoheterotrophic 1095:1112 chemoheterotrophic 1095:1112 All three strains were aerobic, chemoheterotrophic mesophiles with a broad temperature range for growth and a moderately acidic pH optimum. 26486590 2 35 theme family 159:164 arg1 Acidobacteriaceae 166:182 the family Acidobacteriaceae 155:182 the family Acidobacteriaceae 155:182 nov., acidobacteria isolated from Namibian soils, and emended description of the family Acidobacteriaceae. 26486590 16 36 theme riparius 1789:1796 arg1 nov. 1767:1770 the novel genus Occallatibacter gen. nov. 1730:1770 the novel genus Occallatibacter gen. nov. 1730:1770 Based on these characteristics, the three isolates are assigned to two novel species of the novel genus Occallatibacter gen. nov., Occallatibacter riparius sp. 26486590 16 36 theme riparius 1789:1796 arg1 sp 1798:1799 Occallatibacter riparius sp 1773:1799 Occallatibacter riparius sp 1773:1799 Based on these characteristics, the three isolates are assigned to two novel species of the novel genus Occallatibacter gen. nov., Occallatibacter riparius sp. 26486590 8 37 theme bright 1043:1048 arg1 colour 1055:1060 a bright pink colour 1041:1060 a bright pink colour 1041:1060 Colonies of strains 277T and 307 were white to cream and light pink, respectively, while strain A2-1cT displayed a bright pink colour. 26486590 10 38 theme energy 1277:1282 arg1 sources 1284:1290 the preferred carbon and energy sources 1252:1290 sources 1284:1290 Sugars and complex proteinaceous substrates were the preferred carbon and energy sources. 26486590 18 39 theme strain 1951:1956 arg1 26946T 1986:1991  = DSM 25170T = LMG 26946T 1966:1991  = DSM 25170T = LMG 26946T 1966:1991 nov. [type strain A2-1cT ( = DSM 25170T = LMG 26946T)]. 26486590 18 39 theme strain 1951:1956 arg1 A2-1cT 1958:1963 nov. [type strain A2-1cT 1940:1963 nov. [type strain A2-1cT ( = DSM 25170T = LMG 26946T) 1940:1992 nov. [type strain A2-1cT ( = DSM 25170T = LMG 26946T)]. 26486590 17 40 theme 25168T = LMG 1833:1844 arg1 26948T 1846:1851  = DSM 25168T = LMG 26948T 1826:1851  = DSM 25168T = LMG 26948T 1826:1851 nov. [type strain 277T ( = DSM 25168T = LMG 26948T) and reference strain 307 ( = DSM 25169 = LMG 26947)] and Occallatibacter savannae sp. 26486590 17 40 theme 25168T = LMG 1833:1844 arg1 strain 1813:1818 nov. [type strain 277T 1802:1823 nov. [type strain 277T ( = DSM 25168T = LMG 26948T) 1802:1852 nov. [type strain 277T ( = DSM 25168T = LMG 26948T) and reference strain 307 ( = DSM 25169 = LMG 26947)] and Occallatibacter savannae sp. 26486590 2 41 theme Namibian 112:119 arg1 soils 121:125 Namibian soils 112:125 Namibian soils 112:125 nov., acidobacteria isolated from Namibian soils, and emended description of the family Acidobacteriaceae. 26486590 7 42 theme thick 858:862 arg1 envelope 869:876 a thick cell envelope 856:876 a thick cell envelope 856:876 Ultrastructural analyses revealed a thick cell envelope, resulting mainly from a thick periplasmic space. 26486590 4 43 theme gene 371:374 arg1 analyses 385:392 16S rRNA gene sequence analyses 362:392 16S rRNA gene sequence analyses 362:392 16S rRNA gene sequence analyses placed them within subdivision 1 of the Acidobacteria and revealed 100 % similarity between strains 277T and 307 and 98.2 % similarity between A2-1cT and the former two strains. 26486590 17 44 theme reference 1858:1866 arg1 strain 1868:1873 reference strain 307 1858:1877 reference strain 307 1858:1877 nov. [type strain 277T ( = DSM 25168T = LMG 26948T) and reference strain 307 ( = DSM 25169 = LMG 26947)] and Occallatibacter savannae sp. 26486590 4 45 theme former 552:557 arg1 strains 563:569 the former two strains 548:569 the former two strains 548:569 16S rRNA gene sequence analyses placed them within subdivision 1 of the Acidobacteria and revealed 100 % similarity between strains 277T and 307 and 98.2 % similarity between A2-1cT and the former two strains. 26486590 2 46 theme emended 132:138 arg1 description 140:150 emended description 132:150 emended description of the family Acidobacteriaceae 132:182 nov., acidobacteria isolated from Namibian soils, and emended description of the family Acidobacteriaceae. 26486590 9 47 theme temperature 1138:1148 arg1 range 1150:1154 a broad temperature range 1130:1154 a broad temperature range for growth and a moderately acidic pH optimum 1130:1200 All three strains were aerobic, chemoheterotrophic mesophiles with a broad temperature range for growth and a moderately acidic pH optimum. 26486590 7 48 theme Ultrastructural 822:836 arg1 analyses 838:845 Ultrastructural analyses 822:845 Ultrastructural analyses 822:845 Ultrastructural analyses revealed a thick cell envelope, resulting mainly from a thick periplasmic space. 26486590 16 49 theme novel 1734:1738 arg1 nov. 1767:1770 the novel genus Occallatibacter gen. nov. 1730:1770 the novel genus Occallatibacter gen. nov. 1730:1770 Based on these characteristics, the three isolates are assigned to two novel species of the novel genus Occallatibacter gen. nov., Occallatibacter riparius sp. 26486590 16 49 theme novel 1734:1738 arg1 sp 1798:1799 Occallatibacter riparius sp 1773:1799 Occallatibacter riparius sp 1773:1799 Based on these characteristics, the three isolates are assigned to two novel species of the novel genus Occallatibacter gen. nov., Occallatibacter riparius sp. 26486590 15 50 dep strains 1568:1574 arg1 277T 1576:1579 277T 1576:1579 277T 1576:1579 The DNA G+C contents of strains 277T, 307 and A2-1cT were 59.6, 59.9 and 58.5 mol%, respectively. 26486590 15 50 dep strains 1568:1574 arg1 A2-1cT 1590:1595 A2-1cT 1590:1595 A2-1cT 1590:1595 The DNA G+C contents of strains 277T, 307 and A2-1cT were 59.6, 59.9 and 58.5 mol%, respectively. 26486590 15 50 dep strains 1568:1574 arg1 strains 1568:1574 strains 277T, 307 and A2-1cT 1568:1595 strains 277T, 307 and A2-1cT 1568:1595 The DNA G+C contents of strains 277T, 307 and A2-1cT were 59.6, 59.9 and 58.5 mol%, respectively. 26486590 15 50 dep strains 1568:1574 arg1 307 1582:1584 307 1582:1584 307 1582:1584 The DNA G+C contents of strains 277T, 307 and A2-1cT were 59.6, 59.9 and 58.5 mol%, respectively. 26486590 16 51 theme Occallatibacter 1746:1760 arg1 nov. 1767:1770 the novel genus Occallatibacter gen. nov. 1730:1770 the novel genus Occallatibacter gen. nov. 1730:1770 Based on these characteristics, the three isolates are assigned to two novel species of the novel genus Occallatibacter gen. nov., Occallatibacter riparius sp. 26486590 16 51 theme Occallatibacter 1746:1760 arg1 sp 1798:1799 Occallatibacter riparius sp 1773:1799 Occallatibacter riparius sp 1773:1799 Based on these characteristics, the three isolates are assigned to two novel species of the novel genus Occallatibacter gen. nov., Occallatibacter riparius sp. 26486590 4 52 theme 16S 362:364 arg1 analyses 385:392 16S rRNA gene sequence analyses 362:392 16S rRNA gene sequence analyses 362:392 16S rRNA gene sequence analyses placed them within subdivision 1 of the Acidobacteria and revealed 100 % similarity between strains 277T and 307 and 98.2 % similarity between A2-1cT and the former two strains. 26486590 15 53 theme strains 1568:1574 arg1 % 1625:1625 59.6, 59.9 and 58.5 mol% 1602:1625 % 1625:1625 The DNA G+C contents of strains 277T, 307 and A2-1cT were 59.6, 59.9 and 58.5 mol%, respectively. 26486590 15 53 theme strains 1568:1574 arg1 contents 1556:1563 The DNA G+C contents 1544:1563 The DNA G+C contents of strains 277T, 307 and A2-1cT 1544:1595 The DNA G+C contents of strains 277T, 307 and A2-1cT were 59.6, 59.9 and 58.5 mol%, respectively. 26486590 16 54 theme nov. 1767:1770 arg1 species 1719:1725 two novel species 1709:1725 two novel species of the novel genus Occallatibacter gen. nov., Occallatibacter riparius sp 1709:1799 Based on these characteristics, the three isolates are assigned to two novel species of the novel genus Occallatibacter gen. nov., Occallatibacter riparius sp. 26486590 17 55 theme nov. 1802:1805 arg1 25169 = LMG 1887:1897  = DSM 25169 = LMG 26947 1880:1903  = DSM 25169 = LMG 26947 1880:1903 nov. [type strain 277T ( = DSM 25168T = LMG 26948T) and reference strain 307 ( = DSM 25169 = LMG 26947)] and Occallatibacter savannae sp. 26486590 17 55 theme nov. 1802:1805 arg1 strain 1813:1818 nov. [type strain 277T 1802:1823 nov. [type strain 277T ( = DSM 25168T = LMG 26948T) 1802:1852 nov. [type strain 277T ( = DSM 25168T = LMG 26948T) and reference strain 307 ( = DSM 25169 = LMG 26947)] and Occallatibacter savannae sp. 26486590 17 55 theme nov. 1802:1805 arg1 26948T 1846:1851  = DSM 25168T = LMG 26948T 1826:1851  = DSM 25168T = LMG 26948T 1826:1851 nov. [type strain 277T ( = DSM 25168T = LMG 26948T) and reference strain 307 ( = DSM 25169 = LMG 26947)] and Occallatibacter savannae sp. 26486590 12 56 theme major 1334:1338 arg1 MK-7 1379:1382 MK-7 1379:1382 MK-7 1379:1382 The major quinone in all three strains was MK-8; MK-7 occurred in strain A2-1cT as a minor compound. 26486590 12 56 theme major 1334:1338 arg1 quinone 1340:1346 The major quinone 1330:1346 The major quinone in all three strains 1330:1367 The major quinone in all three strains was MK-8; MK-7 occurred in strain A2-1cT as a minor compound. 26486590 19 57 theme several 2010:2016 arg1 taxa 2043:2046 several other recently described taxa 2010:2046 several other recently described taxa 2010:2046 Together with several other recently described taxa, the novel isolates provide the basis for an emended description of the established family Acidobacteriaceae. 26486590 15 58 theme 59.6 1602:1605 arg1 % 1625:1625 59.6, 59.9 and 58.5 mol% 1602:1625 % 1625:1625 The DNA G+C contents of strains 277T, 307 and A2-1cT were 59.6, 59.9 and 58.5 mol%, respectively. 26486590 15 58 theme 59.6 1602:1605 arg1 contents 1556:1563 The DNA G+C contents 1544:1563 The DNA G+C contents of strains 277T, 307 and A2-1cT 1544:1595 The DNA G+C contents of strains 277T, 307 and A2-1cT were 59.6, 59.9 and 58.5 mol%, respectively. 26486590 16 59 theme Occallatibacter 1773:1787 arg1 nov. 1767:1770 the novel genus Occallatibacter gen. nov. 1730:1770 the novel genus Occallatibacter gen. nov. 1730:1770 Based on these characteristics, the three isolates are assigned to two novel species of the novel genus Occallatibacter gen. nov., Occallatibacter riparius sp. 26486590 16 59 theme Occallatibacter 1773:1787 arg1 sp 1798:1799 Occallatibacter riparius sp 1773:1799 Occallatibacter riparius sp 1773:1799 Based on these characteristics, the three isolates are assigned to two novel species of the novel genus Occallatibacter gen. nov., Occallatibacter riparius sp. 26486590 3 60 theme river-bank 277:286 arg1 soil 288:291 a Namibian river-bank soil 266:291 a Namibian river-bank soil (strains 277T and 307) 266:314 Three Gram-negative, non-spore-forming, encapsulated bacteria were isolated from a Namibian river-bank soil (strains 277T and 307) and a semiarid savannah soil (strain A2-1cT). 26486590 3 60 theme river-bank 277:286 arg1 strains 294:300 strains 277T and 307 294:313 strains 277T and 307 294:313 Three Gram-negative, non-spore-forming, encapsulated bacteria were isolated from a Namibian river-bank soil (strains 277T and 307) and a semiarid savannah soil (strain A2-1cT). 26486590 4 61 theme Acidobacteria 434:446 arg1 subdivision 413:423 subdivision 1 413:425 subdivision 1 of the Acidobacteria 413:446 16S rRNA gene sequence analyses placed them within subdivision 1 of the Acidobacteria and revealed 100 % similarity between strains 277T and 307 and 98.2 % similarity between A2-1cT and the former two strains. 26486590 11 62 theme few 1295:1297 arg1 polysaccharides 1299:1313 A few polysaccharides 1293:1313 A few polysaccharides 1293:1313 A few polysaccharides were degraded. 26486590 9 63 theme pH 1191:1192 arg1 optimum 1194:1200 a moderately acidic pH optimum 1171:1200 a moderately acidic pH optimum 1171:1200 All three strains were aerobic, chemoheterotrophic mesophiles with a broad temperature range for growth and a moderately acidic pH optimum. 26486590 17 64 dep sp 1936:1937 arg1 25169 = LMG 1887:1897  = DSM 25169 = LMG 26947 1880:1903  = DSM 25169 = LMG 26947 1880:1903 nov. [type strain 277T ( = DSM 25168T = LMG 26948T) and reference strain 307 ( = DSM 25169 = LMG 26947)] and Occallatibacter savannae sp. 26486590 17 64 dep sp 1936:1937 arg1 strain 1813:1818 nov. [type strain 277T 1802:1823 nov. [type strain 277T ( = DSM 25168T = LMG 26948T) 1802:1852 nov. [type strain 277T ( = DSM 25168T = LMG 26948T) and reference strain 307 ( = DSM 25169 = LMG 26947)] and Occallatibacter savannae sp. 26486590 17 64 dep sp 1936:1937 arg1 savannae 1927:1934 savannae 1927:1934 savannae 1927:1934 nov. [type strain 277T ( = DSM 25168T = LMG 26948T) and reference strain 307 ( = DSM 25169 = LMG 26947)] and Occallatibacter savannae sp. 26486590 17 64 dep sp 1936:1937 arg1 strain 1868:1873 reference strain 307 1858:1877 reference strain 307 1858:1877 nov. [type strain 277T ( = DSM 25168T = LMG 26948T) and reference strain 307 ( = DSM 25169 = LMG 26947)] and Occallatibacter savannae sp. 26486590 17 64 dep sp 1936:1937 arg1 26948T 1846:1851  = DSM 25168T = LMG 26948T 1826:1851  = DSM 25168T = LMG 26948T 1826:1851 nov. [type strain 277T ( = DSM 25168T = LMG 26948T) and reference strain 307 ( = DSM 25169 = LMG 26947)] and Occallatibacter savannae sp. 26486590 1 65 dep sp 74:75 arg1 Occallatibacter 49:63 Occallatibacter 49:63 Occallatibacter 49:63 nov. and Occallatibacter savannae sp. 26486590 1 65 dep sp 74:75 arg1 nov. 40:43 nov. 40:43 nov. 40:43 nov. and Occallatibacter savannae sp. 26486590 15 66 theme DNA 1548:1550 arg1 % 1625:1625 59.6, 59.9 and 58.5 mol% 1602:1625 % 1625:1625 The DNA G+C contents of strains 277T, 307 and A2-1cT were 59.6, 59.9 and 58.5 mol%, respectively. 26486590 15 66 theme DNA 1548:1550 arg1 contents 1556:1563 The DNA G+C contents 1544:1563 The DNA G+C contents of strains 277T, 307 and A2-1cT 1544:1595 The DNA G+C contents of strains 277T, 307 and A2-1cT were 59.6, 59.9 and 58.5 mol%, respectively. 26486590 15 67 theme 58.5 mol 1617:1624 arg1 % 1625:1625 59.6, 59.9 and 58.5 mol% 1602:1625 % 1625:1625 The DNA G+C contents of strains 277T, 307 and A2-1cT were 59.6, 59.9 and 58.5 mol%, respectively. 26486590 15 67 theme 58.5 mol 1617:1624 arg1 contents 1556:1563 The DNA G+C contents 1544:1563 The DNA G+C contents of strains 277T, 307 and A2-1cT 1544:1595 The DNA G+C contents of strains 277T, 307 and A2-1cT were 59.6, 59.9 and 58.5 mol%, respectively. 26486590 5 68 theme type 722:725 arg1 strains 727:733 the type strains 718:733 the type strains 718:733 The closest relatives with validly published names were Telmatobacter bradus, Acidicapsa borealis and Acidicapsa ligni (94.7-95.9 % similarity to the type strains). 26486590 16 69 theme novel 1713:1717 arg1 species 1719:1725 two novel species 1709:1725 two novel species of the novel genus Occallatibacter gen. nov., Occallatibacter riparius sp 1709:1799 Based on these characteristics, the three isolates are assigned to two novel species of the novel genus Occallatibacter gen. nov., Occallatibacter riparius sp. 26486590 18 70 theme 25170T = LMG 1973:1984 arg1 26946T 1986:1991  = DSM 25170T = LMG 26946T 1966:1991  = DSM 25170T = LMG 26946T 1966:1991 nov. [type strain A2-1cT ( = DSM 25170T = LMG 26946T)]. 26486590 18 70 theme 25170T = LMG 1973:1984 arg1 A2-1cT 1958:1963 nov. [type strain A2-1cT 1940:1963 nov. [type strain A2-1cT ( = DSM 25170T = LMG 26946T) 1940:1992 nov. [type strain A2-1cT ( = DSM 25170T = LMG 26946T)]. 26486590 3 71 theme semiarid 322:329 arg1 soil 340:343 a semiarid savannah soil 320:343 a semiarid savannah soil (strain A2-1cT) 320:359 Three Gram-negative, non-spore-forming, encapsulated bacteria were isolated from a Namibian river-bank soil (strains 277T and 307) and a semiarid savannah soil (strain A2-1cT). 26486590 3 71 theme semiarid 322:329 arg1 A2-1cT 353:358 strain A2-1cT 346:358 strain A2-1cT 346:358 Three Gram-negative, non-spore-forming, encapsulated bacteria were isolated from a Namibian river-bank soil (strains 277T and 307) and a semiarid savannah soil (strain A2-1cT). 26486590 3 72 dep Gram-negative 191:203 arg1 encapsulated 225:236 encapsulated 225:236 encapsulated 225:236 Three Gram-negative, non-spore-forming, encapsulated bacteria were isolated from a Namibian river-bank soil (strains 277T and 307) and a semiarid savannah soil (strain A2-1cT). 26486590 3 72 dep Gram-negative 191:203 arg1 non-spore-forming 206:222 non-spore-forming 206:222 non-spore-forming 206:222 Three Gram-negative, non-spore-forming, encapsulated bacteria were isolated from a Namibian river-bank soil (strains 277T and 307) and a semiarid savannah soil (strain A2-1cT). 26486590 5 73 theme % 702:702 arg1 similarity 704:713 94.7-95.9 % similarity 692:713 94.7-95.9 % similarity to the type strains 692:733 The closest relatives with validly published names were Telmatobacter bradus, Acidicapsa borealis and Acidicapsa ligni (94.7-95.9 % similarity to the type strains). 26486590 19 74 theme family 2132:2137 arg1 Acidobacteriaceae 2139:2155 the established family Acidobacteriaceae 2116:2155 the established family Acidobacteriaceae 2116:2155 Together with several other recently described taxa, the novel isolates provide the basis for an emended description of the established family Acidobacteriaceae. 26486590 3 75 theme strain 346:351 arg1 soil 340:343 a semiarid savannah soil 320:343 a semiarid savannah soil (strain A2-1cT) 320:359 Three Gram-negative, non-spore-forming, encapsulated bacteria were isolated from a Namibian river-bank soil (strains 277T and 307) and a semiarid savannah soil (strain A2-1cT). 26486590 3 75 theme strain 346:351 arg1 A2-1cT 353:358 strain A2-1cT 346:358 strain A2-1cT 346:358 Three Gram-negative, non-spore-forming, encapsulated bacteria were isolated from a Namibian river-bank soil (strains 277T and 307) and a semiarid savannah soil (strain A2-1cT). 26486590 5 76 theme closest 576:582 arg1 relatives 584:592 The closest relatives 572:592 The closest relatives with validly published names 572:621 The closest relatives with validly published names were Telmatobacter bradus, Acidicapsa borealis and Acidicapsa ligni (94.7-95.9 % similarity to the type strains). 26486590 5 76 theme closest 576:582 arg1 Telmatobacter 628:640 Telmatobacter 628:640 Telmatobacter 628:640 The closest relatives with validly published names were Telmatobacter bradus, Acidicapsa borealis and Acidicapsa ligni (94.7-95.9 % similarity to the type strains). 26486590 1 77 theme savannae 65:72 arg1 sp 74:75 savannae sp 65:75 savannae sp 65:75 nov. and Occallatibacter savannae sp. 26486590 5 78 dep Acidicapsa 650:659 arg1 borealis 661:668 borealis 661:668 Acidicapsa borealis 650:668 The closest relatives with validly published names were Telmatobacter bradus, Acidicapsa borealis and Acidicapsa ligni (94.7-95.9 % similarity to the type strains). 26486590 4 79 theme % 465:465 arg1 similarity 467:476 100 % similarity 461:476 100 % similarity between strains 277T and 307 and 98.2 % similarity between A2-1cT and the former two strains 461:569 16S rRNA gene sequence analyses placed them within subdivision 1 of the Acidobacteria and revealed 100 % similarity between strains 277T and 307 and 98.2 % similarity between A2-1cT and the former two strains. 26486590 3 80 theme Gram-negative 191:203 arg1 bacteria 238:245 Three Gram-negative, non-spore-forming, encapsulated bacteria 185:245 Three Gram-negative, non-spore-forming, encapsulated bacteria 185:245 Three Gram-negative, non-spore-forming, encapsulated bacteria were isolated from a Namibian river-bank soil (strains 277T and 307) and a semiarid savannah soil (strain A2-1cT). 26486590 10 81 theme proteinaceous 1222:1234 arg1 substrates 1236:1245 complex proteinaceous substrates 1214:1245 complex proteinaceous substrates 1214:1245 Sugars and complex proteinaceous substrates were the preferred carbon and energy sources. 26486590 10 81 theme proteinaceous 1222:1234 arg1 Sugars 1203:1208 Sugars 1203:1208 Sugars 1203:1208 Sugars and complex proteinaceous substrates were the preferred carbon and energy sources. 26486590 10 81 theme proteinaceous 1222:1234 arg1 carbon 1266:1271 the preferred carbon and energy sources 1252:1290 carbon 1266:1271 Sugars and complex proteinaceous substrates were the preferred carbon and energy sources. 26486590 13 82 theme Major 1431:1435 arg1 acids 1443:1447 Major fatty acids 1431:1447 Major fatty acids 1431:1447 Major fatty acids were iso-C15 : 0 and iso-C17 : 1ω7c. 26486590 0 83 theme riparius 16:23 arg1 nov. 30:33 Occallatibacter riparius gen. nov. 0:33 Occallatibacter riparius gen. nov. 0:33 Occallatibacter riparius gen. nov., sp. 26486590 4 84 dep % 516:516 arg1 98.2  511:515 98.2  511:515 98.2  511:515 16S rRNA gene sequence analyses placed them within subdivision 1 of the Acidobacteria and revealed 100 % similarity between strains 277T and 307 and 98.2 % similarity between A2-1cT and the former two strains. 26486590 4 84 dep % 516:516 arg1 307 503:505 307 503:505 307 503:505 16S rRNA gene sequence analyses placed them within subdivision 1 of the Acidobacteria and revealed 100 % similarity between strains 277T and 307 and 98.2 % similarity between A2-1cT and the former two strains. 26486590 7 85 theme thick 903:907 arg1 space 921:925 a thick periplasmic space 901:925 a thick periplasmic space 901:925 Ultrastructural analyses revealed a thick cell envelope, resulting mainly from a thick periplasmic space. 26486590 18 86 theme [type 1945:1949 arg1 26946T 1986:1991  = DSM 25170T = LMG 26946T 1966:1991  = DSM 25170T = LMG 26946T 1966:1991 nov. [type strain A2-1cT ( = DSM 25170T = LMG 26946T)]. 26486590 18 86 theme [type 1945:1949 arg1 A2-1cT 1958:1963 nov. [type strain A2-1cT 1940:1963 nov. [type strain A2-1cT ( = DSM 25170T = LMG 26946T) 1940:1992 nov. [type strain A2-1cT ( = DSM 25170T = LMG 26946T)]. 26486590 2 87 theme Acidobacteriaceae 166:182 arg1 nov. 78:81 nov. 78:81 nov. 78:81 nov., acidobacteria isolated from Namibian soils, and emended description of the family Acidobacteriaceae. 26486590 2 87 theme Acidobacteriaceae 166:182 arg1 acidobacteria 84:96 acidobacteria 84:96 acidobacteria isolated from Namibian soils 84:125 nov., acidobacteria isolated from Namibian soils, and emended description of the family Acidobacteriaceae. 26486590 2 87 theme Acidobacteriaceae 166:182 arg1 description 140:150 emended description 132:150 emended description of the family Acidobacteriaceae 132:182 nov., acidobacteria isolated from Namibian soils, and emended description of the family Acidobacteriaceae. 26486590 10 88 theme preferred 1256:1264 arg1 substrates 1236:1245 complex proteinaceous substrates 1214:1245 complex proteinaceous substrates 1214:1245 Sugars and complex proteinaceous substrates were the preferred carbon and energy sources. 26486590 10 88 theme preferred 1256:1264 arg1 Sugars 1203:1208 Sugars 1203:1208 Sugars 1203:1208 Sugars and complex proteinaceous substrates were the preferred carbon and energy sources. 26486590 10 88 theme preferred 1256:1264 arg1 carbon 1266:1271 the preferred carbon and energy sources 1252:1290 carbon 1266:1271 Sugars and complex proteinaceous substrates were the preferred carbon and energy sources. 26486590 15 89 theme G+C 1552:1554 arg1 % 1625:1625 59.6, 59.9 and 58.5 mol% 1602:1625 % 1625:1625 The DNA G+C contents of strains 277T, 307 and A2-1cT were 59.6, 59.9 and 58.5 mol%, respectively. 26486590 15 89 theme G+C 1552:1554 arg1 contents 1556:1563 The DNA G+C contents 1544:1563 The DNA G+C contents of strains 277T, 307 and A2-1cT 1544:1595 The DNA G+C contents of strains 277T, 307 and A2-1cT were 59.6, 59.9 and 58.5 mol%, respectively. 26486590 4 90 dep strains 486:492 arg1 similarity 518:527 307 and 98.2 % similarity 503:527 307 and 98.2 % similarity 503:527 16S rRNA gene sequence analyses placed them within subdivision 1 of the Acidobacteria and revealed 100 % similarity between strains 277T and 307 and 98.2 % similarity between A2-1cT and the former two strains. 26486590 4 90 dep strains 486:492 arg1 strains 486:492 strains 277T and 307 and 98.2 % similarity 486:527 strains 277T and 307 and 98.2 % similarity 486:527 16S rRNA gene sequence analyses placed them within subdivision 1 of the Acidobacteria and revealed 100 % similarity between strains 277T and 307 and 98.2 % similarity between A2-1cT and the former two strains. 26486590 4 90 dep strains 486:492 arg1 277T 494:497 277T 494:497 277T 494:497 16S rRNA gene sequence analyses placed them within subdivision 1 of the Acidobacteria and revealed 100 % similarity between strains 277T and 307 and 98.2 % similarity between A2-1cT and the former two strains. 26486590 8 91 theme pink 1050:1053 arg1 colour 1055:1060 a bright pink colour 1041:1060 a bright pink colour 1041:1060 Colonies of strains 277T and 307 were white to cream and light pink, respectively, while strain A2-1cT displayed a bright pink colour. 26486590 6 92 theme binary 806:811 arg1 fission 813:819 binary fission 806:819 binary fission 806:819 Cells of all three strains were rod-shaped and motile and divided by binary fission. 26486590 0 93 dep sp 36:37 arg1 nov. 30:33 Occallatibacter riparius gen. nov. 0:33 Occallatibacter riparius gen. nov. 0:33 Occallatibacter riparius gen. nov., sp. 26486590 14 94 theme significant 1523:1533 arg1 amounts 1535:1541 significant amounts 1523:1541 significant amounts 1523:1541 In addition, iso-C17 : 0 occurred in significant amounts. 26486590 19 95 theme other 2018:2022 arg1 taxa 2043:2046 several other recently described taxa 2010:2046 several other recently described taxa 2010:2046 Together with several other recently described taxa, the novel isolates provide the basis for an emended description of the established family Acidobacteriaceae. 26486590 5 96 with relatives 584:592 arg1 names 617:621 validly published names 599:621 validly published names 599:621 The closest relatives with validly published names were Telmatobacter bradus, Acidicapsa borealis and Acidicapsa ligni (94.7-95.9 % similarity to the type strains). 26486590 9 97 theme aerobic 1086:1092 arg1 mesophiles 1114:1123 aerobic, chemoheterotrophic mesophiles 1086:1123 aerobic, chemoheterotrophic mesophiles 1086:1123 All three strains were aerobic, chemoheterotrophic mesophiles with a broad temperature range for growth and a moderately acidic pH optimum. 26486590 7 98 theme cell 864:867 arg1 envelope 869:876 a thick cell envelope 856:876 a thick cell envelope 856:876 Ultrastructural analyses revealed a thick cell envelope, resulting mainly from a thick periplasmic space. 26486590 9 99 with mesophiles 1114:1123 arg1 range 1150:1154 a broad temperature range 1130:1154 a broad temperature range for growth and a moderately acidic pH optimum 1130:1200 All three strains were aerobic, chemoheterotrophic mesophiles with a broad temperature range for growth and a moderately acidic pH optimum. 26486590 17 100 theme  = DSM 1826:1831 arg1 26948T 1846:1851  = DSM 25168T = LMG 26948T 1826:1851  = DSM 25168T = LMG 26948T 1826:1851 nov. [type strain 277T ( = DSM 25168T = LMG 26948T) and reference strain 307 ( = DSM 25169 = LMG 26947)] and Occallatibacter savannae sp. 26486590 17 100 theme  = DSM 1826:1831 arg1 strain 1813:1818 nov. [type strain 277T 1802:1823 nov. [type strain 277T ( = DSM 25168T = LMG 26948T) 1802:1852 nov. [type strain 277T ( = DSM 25168T = LMG 26948T) and reference strain 307 ( = DSM 25169 = LMG 26947)] and Occallatibacter savannae sp. 26486590 12 101 theme minor 1415:1419 arg1 compound 1421:1428 a minor compound 1413:1428 a minor compound 1413:1428 The major quinone in all three strains was MK-8; MK-7 occurred in strain A2-1cT as a minor compound. 26486590 3 102 attach isolated 252:259 arg1 soil 288:291 a Namibian river-bank soil 266:291 a Namibian river-bank soil (strains 277T and 307) 266:314 Three Gram-negative, non-spore-forming, encapsulated bacteria were isolated from a Namibian river-bank soil (strains 277T and 307) and a semiarid savannah soil (strain A2-1cT). 26486590 3 102 attach isolated 252:259 arg1 soil 340:343 a semiarid savannah soil 320:343 a semiarid savannah soil (strain A2-1cT) 320:359 Three Gram-negative, non-spore-forming, encapsulated bacteria were isolated from a Namibian river-bank soil (strains 277T and 307) and a semiarid savannah soil (strain A2-1cT). 26486590 3 102 attach isolated 252:259 arg1 A2-1cT 353:358 strain A2-1cT 346:358 strain A2-1cT 346:358 Three Gram-negative, non-spore-forming, encapsulated bacteria were isolated from a Namibian river-bank soil (strains 277T and 307) and a semiarid savannah soil (strain A2-1cT). 26486590 3 102 attach isolated 252:259 arg2 bacteria 238:245 Three Gram-negative, non-spore-forming, encapsulated bacteria 185:245 Three Gram-negative, non-spore-forming, encapsulated bacteria 185:245 Three Gram-negative, non-spore-forming, encapsulated bacteria were isolated from a Namibian river-bank soil (strains 277T and 307) and a semiarid savannah soil (strain A2-1cT). 26486590 3 102 attach isolated 252:259 arg1 strains 294:300 strains 277T and 307 294:313 strains 277T and 307 294:313 Three Gram-negative, non-spore-forming, encapsulated bacteria were isolated from a Namibian river-bank soil (strains 277T and 307) and a semiarid savannah soil (strain A2-1cT). 29132358 4 0 theme substrate 938:946 arg1 consumption 948:958 substrate consumption 938:958 substrate consumption 938:958 As a continuation of that research, in the present study HTS FTIR was evaluated as a unified method for simultaneous quantification of intra- and extracellular metabolites and substrate consumption. 29132358 9 1 theme citric 1897:1902 arg1 acid 1904:1907 citric acid 1897:1907 citric acid 1897:1907 PLSR results for HTS measurements were very similar to the results obtained with ATR methodology, with high coefficients of determination (0.91-0.98) and low error values (4.9-8.6%) for both glucose and citric acid estimates. 29132358 12 2 theme single-cell 2357:2367 arg1 production 2373:2382 single-cell oil production 2357:2382 single-cell oil production 2357:2382 It can be anticipated that the approach, demonstrated here on single-cell oil production by filamentous fungi, can find general application in screening studies of microbial bioprocesses, such as production of single-cell proteins, biopolymers, polysaccharides, carboxylic acids, and other type of metabolites. 29132358 2 3 theme high 382:385 arg1 micro-bioreactors 398:414 high throughput micro-bioreactors 382:414 high throughput micro-bioreactors 382:414 We have assessed Fourier transform infrared spectroscopy (FTIR), in combination with high throughput micro-bioreactors and multivariate statistical analyses, for analysis of metabolites in high-throughput screening of microbial bioprocesses. 29132358 7 4 theme performance 1491:1501 arg1 HPLC 1526:1529 HPLC 1526:1529 HPLC 1526:1529 Glucose and citric acid content of growth media was quantified by high performance liquid chromatography (HPLC). 29132358 7 4 theme performance 1491:1501 arg1 chromatography 1510:1523 high performance liquid chromatography 1486:1523 high performance liquid chromatography (HPLC) 1486:1530 Glucose and citric acid content of growth media was quantified by high performance liquid chromatography (HPLC). 29132358 12 5 theme biopolymers 2527:2537 arg1 production 2491:2500 production 2491:2500 production of single-cell proteins, biopolymers, polysaccharides, carboxylic acids, and other type of metabolites 2491:2603 It can be anticipated that the approach, demonstrated here on single-cell oil production by filamentous fungi, can find general application in screening studies of microbial bioprocesses, such as production of single-cell proteins, biopolymers, polysaccharides, carboxylic acids, and other type of metabolites. 29132358 10 6 theme intra- 1964:1969 arg1 metabolites 1989:1999 intra- and extracellular metabolites 1964:1999 intra- and extracellular metabolites 1964:1999 CONCLUSIONS The study has demonstrated that intra- and extracellular metabolites, as well as nutrients in the cultivation medium, can be monitored by a unified approach by HTS FTIR. 29132358 9 7 theme HTS 1711:1713 arg1 measurements 1715:1726 HTS measurements 1711:1726 HTS measurements 1711:1726 PLSR results for HTS measurements were very similar to the results obtained with ATR methodology, with high coefficients of determination (0.91-0.98) and low error values (4.9-8.6%) for both glucose and citric acid estimates. 29132358 12 8 theme proteins 2517:2524 arg1 production 2491:2500 production 2491:2500 production of single-cell proteins, biopolymers, polysaccharides, carboxylic acids, and other type of metabolites 2491:2603 It can be anticipated that the approach, demonstrated here on single-cell oil production by filamentous fungi, can find general application in screening studies of microbial bioprocesses, such as production of single-cell proteins, biopolymers, polysaccharides, carboxylic acids, and other type of metabolites. 29132358 11 9 theme microbial 2271:2279 arg1 bioprocesses 2281:2292 microbial bioprocesses 2271:2292 microbial bioprocesses 2271:2292 The proof-of-concept study has validated that HTS FTIR, in combination with Duetz microtiter plate system and chemometrics, can be used for high throughput screening of microbial bioprocesses. 29132358 3 10 from accumulation 716:727 arg1 fungi 755:759 oleaginous filamentous fungi 732:759 oleaginous filamentous fungi 732:759 In our previous study, we have demonstrated that high-throughput (HTS) FTIR can be used for estimating content and composition of intracellular metabolites, namely triglyceride accumulation in oleaginous filamentous fungi. 29132358 6 11 theme total 1333:1337 arg1 ATR 1351:1353 ATR 1351:1353 ATR 1351:1353 RESULTS HTS FTIR analyses of supernatant samples was compared with an attenuated total reflection (ATR) FTIR, which is an established method for bioprocess monitoring. 29132358 6 11 theme total 1333:1337 arg1 reflection 1339:1348 total reflection 1333:1348 an attenuated total reflection (ATR) FTIR 1319:1359 RESULTS HTS FTIR analyses of supernatant samples was compared with an attenuated total reflection (ATR) FTIR, which is an established method for bioprocess monitoring. 29132358 4 12 theme metabolites 922:932 arg1 quantification 879:892 simultaneous quantification 866:892 simultaneous quantification of intra- and extracellular metabolites and substrate consumption 866:958 As a continuation of that research, in the present study HTS FTIR was evaluated as a unified method for simultaneous quantification of intra- and extracellular metabolites and substrate consumption. 29132358 12 13 theme screening 2438:2446 arg1 studies 2448:2454 screening studies 2438:2454 screening studies of microbial bioprocesses, such as production of single-cell proteins, biopolymers, polysaccharides, carboxylic acids, and other type of metabolites 2438:2603 It can be anticipated that the approach, demonstrated here on single-cell oil production by filamentous fungi, can find general application in screening studies of microbial bioprocesses, such as production of single-cell proteins, biopolymers, polysaccharides, carboxylic acids, and other type of metabolites. 29132358 11 14 used used 2233:2236 arg2 FTIR 2152:2155 HTS FTIR 2148:2155 HTS FTIR 2148:2155 The proof-of-concept study has validated that HTS FTIR, in combination with Duetz microtiter plate system and chemometrics, can be used for high throughput screening of microbial bioprocesses. 29132358 7 15 theme acid 1439:1442 arg1 content 1444:1450 Glucose and citric acid content 1420:1450 Glucose and citric acid content of growth media 1420:1466 Glucose and citric acid content of growth media was quantified by high performance liquid chromatography (HPLC). 29132358 7 16 theme growth 1455:1460 arg1 media 1462:1466 growth media 1455:1466 growth media 1455:1466 Glucose and citric acid content of growth media was quantified by high performance liquid chromatography (HPLC). 29132358 12 17 theme microbial 2459:2467 arg1 production 2491:2500 production 2491:2500 production of single-cell proteins, biopolymers, polysaccharides, carboxylic acids, and other type of metabolites 2491:2603 It can be anticipated that the approach, demonstrated here on single-cell oil production by filamentous fungi, can find general application in screening studies of microbial bioprocesses, such as production of single-cell proteins, biopolymers, polysaccharides, carboxylic acids, and other type of metabolites. 29132358 12 17 theme microbial 2459:2467 arg1 bioprocesses 2469:2480 microbial bioprocesses 2459:2480 microbial bioprocesses 2459:2480 It can be anticipated that the approach, demonstrated here on single-cell oil production by filamentous fungi, can find general application in screening studies of microbial bioprocesses, such as production of single-cell proteins, biopolymers, polysaccharides, carboxylic acids, and other type of metabolites. 29132358 10 18 theme extracellular 1975:1987 arg1 metabolites 1989:1999 intra- and extracellular metabolites 1964:1999 intra- and extracellular metabolites 1964:1999 CONCLUSIONS The study has demonstrated that intra- and extracellular metabolites, as well as nutrients in the cultivation medium, can be monitored by a unified approach by HTS FTIR. 29132358 5 19 theme triglyceride 1142:1153 arg1 lipids 1155:1160 triglyceride lipids 1142:1160 triglyceride lipids 1142:1160 As a proof of concept, a high-throughput microcultivation of oleaginous filamentous fungi was conducted in order to monitor production of citric acid (extracellular metabolite) and triglyceride lipids (intracellular metabolites), as well as consumption of glucose in the cultivation medium. 29132358 1 20 theme bottleneck 219:228 arg1 Analyses 171:178 BACKGROUND Analyses 160:178 BACKGROUND Analyses of substrate and metabolites 160:207 BACKGROUND Analyses of substrate and metabolites are often bottleneck activities in high-throughput screening of microbial bioprocesses. 29132358 1 20 theme bottleneck 219:228 arg1 activities 230:239 bottleneck activities 219:239 bottleneck activities in high-throughput screening of microbial bioprocesses 219:294 BACKGROUND Analyses of substrate and metabolites are often bottleneck activities in high-throughput screening of microbial bioprocesses. 29132358 10 21 theme HTS 2092:2094 arg1 FTIR 2096:2099 HTS FTIR 2092:2099 HTS FTIR 2092:2099 CONCLUSIONS The study has demonstrated that intra- and extracellular metabolites, as well as nutrients in the cultivation medium, can be monitored by a unified approach by HTS FTIR. 29132358 3 22 used used 622:625 arg2 FTIR 610:613 high-throughput (HTS) FTIR 588:613 high-throughput (HTS) FTIR 588:613 In our previous study, we have demonstrated that high-throughput (HTS) FTIR can be used for estimating content and composition of intracellular metabolites, namely triglyceride accumulation in oleaginous filamentous fungi. 29132358 0 23 theme microbial 136:144 arg1 bioprocesses 146:157 microbial bioprocesses 136:157 microbial bioprocesses 136:157 FTIR spectroscopy as a unified method for simultaneous analysis of intra- and extracellular metabolites in high-throughput screening of microbial bioprocesses. 29132358 9 24 theme low 1848:1850 arg1 values 1858:1863 low error values 1848:1863 low error values (4.9-8.6%) 1848:1874 PLSR results for HTS measurements were very similar to the results obtained with ATR methodology, with high coefficients of determination (0.91-0.98) and low error values (4.9-8.6%) for both glucose and citric acid estimates. 29132358 9 24 theme low 1848:1850 arg1 % 1873:1873 4.9-8.6% 1866:1873 4.9-8.6% 1866:1873 PLSR results for HTS measurements were very similar to the results obtained with ATR methodology, with high coefficients of determination (0.91-0.98) and low error values (4.9-8.6%) for both glucose and citric acid estimates. 29132358 1 25 from activities 230:239 arg1 screening 260:268 high-throughput screening 244:268 high-throughput screening of microbial bioprocesses 244:294 BACKGROUND Analyses of substrate and metabolites are often bottleneck activities in high-throughput screening of microbial bioprocesses. 29132358 0 26 from analysis 55:62 arg1 screening 123:131 high-throughput screening 107:131 high-throughput screening of microbial bioprocesses 107:157 FTIR spectroscopy as a unified method for simultaneous analysis of intra- and extracellular metabolites in high-throughput screening of microbial bioprocesses. 29132358 7 27 theme citric 1432:1437 arg1 acid 1439:1442 citric acid 1432:1442 citric acid 1432:1442 Glucose and citric acid content of growth media was quantified by high performance liquid chromatography (HPLC). 29132358 5 28 theme extracellular 1112:1124 arg1 acid 1106:1109 citric acid 1099:1109 citric acid (extracellular metabolite) 1099:1136 As a proof of concept, a high-throughput microcultivation of oleaginous filamentous fungi was conducted in order to monitor production of citric acid (extracellular metabolite) and triglyceride lipids (intracellular metabolites), as well as consumption of glucose in the cultivation medium. 29132358 5 28 theme extracellular 1112:1124 arg1 metabolite 1126:1135 extracellular metabolite 1112:1135 extracellular metabolite 1112:1135 As a proof of concept, a high-throughput microcultivation of oleaginous filamentous fungi was conducted in order to monitor production of citric acid (extracellular metabolite) and triglyceride lipids (intracellular metabolites), as well as consumption of glucose in the cultivation medium. 29132358 9 29 theme ATR 1775:1777 arg1 methodology 1779:1789 ATR methodology 1775:1789 ATR methodology 1775:1789 PLSR results for HTS measurements were very similar to the results obtained with ATR methodology, with high coefficients of determination (0.91-0.98) and low error values (4.9-8.6%) for both glucose and citric acid estimates. 29132358 7 30 theme Glucose 1420:1426 arg1 content 1444:1450 Glucose and citric acid content 1420:1450 Glucose and citric acid content of growth media 1420:1466 Glucose and citric acid content of growth media was quantified by high performance liquid chromatography (HPLC). 29132358 6 31 theme supernatant 1281:1291 arg1 samples 1293:1299 supernatant samples 1281:1299 supernatant samples 1281:1299 RESULTS HTS FTIR analyses of supernatant samples was compared with an attenuated total reflection (ATR) FTIR, which is an established method for bioprocess monitoring. 29132358 6 32 theme HTS 1260:1262 arg1 analyses 1269:1276 HTS FTIR analyses 1260:1276 HTS FTIR analyses of supernatant samples 1260:1299 RESULTS HTS FTIR analyses of supernatant samples was compared with an attenuated total reflection (ATR) FTIR, which is an established method for bioprocess monitoring. 29132358 5 33 theme high-throughput 986:1000 arg1 proof 966:970 a proof 964:970 a proof of concept 964:981 As a proof of concept, a high-throughput microcultivation of oleaginous filamentous fungi was conducted in order to monitor production of citric acid (extracellular metabolite) and triglyceride lipids (intracellular metabolites), as well as consumption of glucose in the cultivation medium. 29132358 5 33 theme high-throughput 986:1000 arg1 microcultivation 1002:1017 a high-throughput microcultivation 984:1017 a high-throughput microcultivation of oleaginous filamentous fungi 984:1049 As a proof of concept, a high-throughput microcultivation of oleaginous filamentous fungi was conducted in order to monitor production of citric acid (extracellular metabolite) and triglyceride lipids (intracellular metabolites), as well as consumption of glucose in the cultivation medium. 29132358 8 34 theme least 1541:1545 arg1 PLSR 1566:1569 PLSR 1566:1569 PLSR 1566:1569 Partial least square regression (PLSR) between HPLC glucose and citric acid data and the corresponding FTIR spectral data was used to set up calibration models. 29132358 8 34 theme least 1541:1545 arg1 regression 1554:1563 Partial least square regression 1533:1563 Partial least square regression (PLSR) between HPLC glucose and citric acid data and the corresponding FTIR spectral data 1533:1653 Partial least square regression (PLSR) between HPLC glucose and citric acid data and the corresponding FTIR spectral data was used to set up calibration models. 29132358 2 35 dep Fourier 314:320 arg1 transform 322:330 transform 322:330 transform infrared spectroscopy (FTIR), in combination with high throughput micro-bioreactors and multivariate statistical analyses, for analysis of metabolites in high-throughput screening of microbial bioprocesses 322:536 We have assessed Fourier transform infrared spectroscopy (FTIR), in combination with high throughput micro-bioreactors and multivariate statistical analyses, for analysis of metabolites in high-throughput screening of microbial bioprocesses. 29132358 1 36 theme BACKGROUND 160:169 arg1 activities 230:239 bottleneck activities 219:239 bottleneck activities in high-throughput screening of microbial bioprocesses 219:294 BACKGROUND Analyses of substrate and metabolites are often bottleneck activities in high-throughput screening of microbial bioprocesses. 29132358 1 36 theme BACKGROUND 160:169 arg1 Analyses 171:178 BACKGROUND Analyses 160:178 BACKGROUND Analyses of substrate and metabolites 160:207 BACKGROUND Analyses of substrate and metabolites are often bottleneck activities in high-throughput screening of microbial bioprocesses. 29132358 9 37 theme high 1797:1800 arg1 coefficients 1802:1813 high coefficients 1797:1813 high coefficients of determination (0.91-0.98) 1797:1842 PLSR results for HTS measurements were very similar to the results obtained with ATR methodology, with high coefficients of determination (0.91-0.98) and low error values (4.9-8.6%) for both glucose and citric acid estimates. 29132358 0 38 theme intra- 67:72 arg1 metabolites 92:102 intra- and extracellular metabolites 67:102 intra- and extracellular metabolites in high-throughput screening of microbial bioprocesses 67:157 FTIR spectroscopy as a unified method for simultaneous analysis of intra- and extracellular metabolites in high-throughput screening of microbial bioprocesses. 29132358 8 39 theme square 1547:1552 arg1 PLSR 1566:1569 PLSR 1566:1569 PLSR 1566:1569 Partial least square regression (PLSR) between HPLC glucose and citric acid data and the corresponding FTIR spectral data was used to set up calibration models. 29132358 8 39 theme square 1547:1552 arg1 regression 1554:1563 Partial least square regression 1533:1563 Partial least square regression (PLSR) between HPLC glucose and citric acid data and the corresponding FTIR spectral data 1533:1653 Partial least square regression (PLSR) between HPLC glucose and citric acid data and the corresponding FTIR spectral data was used to set up calibration models. 29132358 11 40 theme proof-of-concept 2106:2121 arg1 study 2123:2127 The proof-of-concept study 2102:2127 The proof-of-concept study 2102:2127 The proof-of-concept study has validated that HTS FTIR, in combination with Duetz microtiter plate system and chemometrics, can be used for high throughput screening of microbial bioprocesses. 29132358 2 41 from screening 502:510 arg1 analysis 459:466 analysis 459:466 analysis of metabolites in high-throughput screening of microbial bioprocesses 459:536 We have assessed Fourier transform infrared spectroscopy (FTIR), in combination with high throughput micro-bioreactors and multivariate statistical analyses, for analysis of metabolites in high-throughput screening of microbial bioprocesses. 29132358 0 42 theme extracellular 78:90 arg1 metabolites 92:102 intra- and extracellular metabolites 67:102 intra- and extracellular metabolites in high-throughput screening of microbial bioprocesses 67:157 FTIR spectroscopy as a unified method for simultaneous analysis of intra- and extracellular metabolites in high-throughput screening of microbial bioprocesses. 29132358 5 43 theme metabolites 1177:1187 arg1 production 1085:1094 production 1085:1094 production of citric acid (extracellular metabolite) and triglyceride lipids (intracellular metabolites) 1085:1188 As a proof of concept, a high-throughput microcultivation of oleaginous filamentous fungi was conducted in order to monitor production of citric acid (extracellular metabolite) and triglyceride lipids (intracellular metabolites), as well as consumption of glucose in the cultivation medium. 29132358 5 43 theme metabolites 1177:1187 arg1 consumption 1202:1212 consumption 1202:1212 consumption of glucose 1202:1223 As a proof of concept, a high-throughput microcultivation of oleaginous filamentous fungi was conducted in order to monitor production of citric acid (extracellular metabolite) and triglyceride lipids (intracellular metabolites), as well as consumption of glucose in the cultivation medium. 29132358 10 44 from metabolites 1989:1999 arg1 medium 2042:2047 the cultivation medium 2026:2047 the cultivation medium 2026:2047 CONCLUSIONS The study has demonstrated that intra- and extracellular metabolites, as well as nutrients in the cultivation medium, can be monitored by a unified approach by HTS FTIR. 29132358 12 45 theme oil 2369:2371 arg1 production 2373:2382 single-cell oil production 2357:2382 single-cell oil production 2357:2382 It can be anticipated that the approach, demonstrated here on single-cell oil production by filamentous fungi, can find general application in screening studies of microbial bioprocesses, such as production of single-cell proteins, biopolymers, polysaccharides, carboxylic acids, and other type of metabolites. 29132358 8 46 theme glucose 1585:1591 arg1 data 1609:1612 HPLC glucose and citric acid data 1580:1612 HPLC glucose and citric acid data 1580:1612 Partial least square regression (PLSR) between HPLC glucose and citric acid data and the corresponding FTIR spectral data was used to set up calibration models. 29132358 2 47 theme statistical 433:443 arg1 analyses 445:452 multivariate statistical analyses 420:452 multivariate statistical analyses 420:452 We have assessed Fourier transform infrared spectroscopy (FTIR), in combination with high throughput micro-bioreactors and multivariate statistical analyses, for analysis of metabolites in high-throughput screening of microbial bioprocesses. 29132358 0 48 theme FTIR 0:3 arg1 spectroscopy 5:16 FTIR spectroscopy 0:16 FTIR spectroscopy 0:16 FTIR spectroscopy as a unified method for simultaneous analysis of intra- and extracellular metabolites in high-throughput screening of microbial bioprocesses. 29132358 11 49 theme HTS 2148:2150 arg1 FTIR 2152:2155 HTS FTIR 2148:2155 HTS FTIR 2148:2155 The proof-of-concept study has validated that HTS FTIR, in combination with Duetz microtiter plate system and chemometrics, can be used for high throughput screening of microbial bioprocesses. 29132358 2 50 theme high-throughput 486:500 arg1 screening 502:510 high-throughput screening 486:510 high-throughput screening of microbial bioprocesses 486:536 We have assessed Fourier transform infrared spectroscopy (FTIR), in combination with high throughput micro-bioreactors and multivariate statistical analyses, for analysis of metabolites in high-throughput screening of microbial bioprocesses. 29132358 8 51 theme citric 1597:1602 arg1 acid 1604:1607 citric acid 1597:1607 citric acid 1597:1607 Partial least square regression (PLSR) between HPLC glucose and citric acid data and the corresponding FTIR spectral data was used to set up calibration models. 29132358 12 52 theme other 2579:2583 arg1 type 2585:2588 other type 2579:2588 other type of metabolites 2579:2603 It can be anticipated that the approach, demonstrated here on single-cell oil production by filamentous fungi, can find general application in screening studies of microbial bioprocesses, such as production of single-cell proteins, biopolymers, polysaccharides, carboxylic acids, and other type of metabolites. 29132358 2 53 theme metabolites 471:481 arg1 analysis 459:466 analysis 459:466 analysis of metabolites in high-throughput screening of microbial bioprocesses 459:536 We have assessed Fourier transform infrared spectroscopy (FTIR), in combination with high throughput micro-bioreactors and multivariate statistical analyses, for analysis of metabolites in high-throughput screening of microbial bioprocesses. 29132358 5 54 theme filamentous 1033:1043 arg1 fungi 1045:1049 oleaginous filamentous fungi 1022:1049 oleaginous filamentous fungi 1022:1049 As a proof of concept, a high-throughput microcultivation of oleaginous filamentous fungi was conducted in order to monitor production of citric acid (extracellular metabolite) and triglyceride lipids (intracellular metabolites), as well as consumption of glucose in the cultivation medium. 29132358 11 55 theme plate 2195:2199 arg1 system 2201:2206 Duetz microtiter plate system 2178:2206 Duetz microtiter plate system 2178:2206 The proof-of-concept study has validated that HTS FTIR, in combination with Duetz microtiter plate system and chemometrics, can be used for high throughput screening of microbial bioprocesses. 29132358 4 56 theme simultaneous 866:877 arg1 quantification 879:892 simultaneous quantification 866:892 simultaneous quantification of intra- and extracellular metabolites and substrate consumption 866:958 As a continuation of that research, in the present study HTS FTIR was evaluated as a unified method for simultaneous quantification of intra- and extracellular metabolites and substrate consumption. 29132358 9 57 with similar 1738:1744 arg1 coefficients 1802:1813 high coefficients 1797:1813 high coefficients of determination (0.91-0.98) 1797:1842 PLSR results for HTS measurements were very similar to the results obtained with ATR methodology, with high coefficients of determination (0.91-0.98) and low error values (4.9-8.6%) for both glucose and citric acid estimates. 29132358 9 57 with similar 1738:1744 arg1 values 1858:1863 low error values 1848:1863 low error values (4.9-8.6%) 1848:1874 PLSR results for HTS measurements were very similar to the results obtained with ATR methodology, with high coefficients of determination (0.91-0.98) and low error values (4.9-8.6%) for both glucose and citric acid estimates. 29132358 9 57 with similar 1738:1744 arg1 % 1873:1873 4.9-8.6% 1866:1873 4.9-8.6% 1866:1873 PLSR results for HTS measurements were very similar to the results obtained with ATR methodology, with high coefficients of determination (0.91-0.98) and low error values (4.9-8.6%) for both glucose and citric acid estimates. 29132358 0 58 theme unified 23:29 arg1 method 31:36 a unified method 21:36 a unified method for simultaneous analysis of intra- and extracellular metabolites in high-throughput screening of microbial bioprocesses 21:157 FTIR spectroscopy as a unified method for simultaneous analysis of intra- and extracellular metabolites in high-throughput screening of microbial bioprocesses. 29132358 5 59 theme glucose 1217:1223 arg1 production 1085:1094 production 1085:1094 production of citric acid (extracellular metabolite) and triglyceride lipids (intracellular metabolites) 1085:1188 As a proof of concept, a high-throughput microcultivation of oleaginous filamentous fungi was conducted in order to monitor production of citric acid (extracellular metabolite) and triglyceride lipids (intracellular metabolites), as well as consumption of glucose in the cultivation medium. 29132358 5 59 theme glucose 1217:1223 arg1 consumption 1202:1212 consumption 1202:1212 consumption of glucose 1202:1223 As a proof of concept, a high-throughput microcultivation of oleaginous filamentous fungi was conducted in order to monitor production of citric acid (extracellular metabolite) and triglyceride lipids (intracellular metabolites), as well as consumption of glucose in the cultivation medium. 29132358 5 60 theme citric 1099:1104 arg1 acid 1106:1109 citric acid 1099:1109 citric acid (extracellular metabolite) 1099:1136 As a proof of concept, a high-throughput microcultivation of oleaginous filamentous fungi was conducted in order to monitor production of citric acid (extracellular metabolite) and triglyceride lipids (intracellular metabolites), as well as consumption of glucose in the cultivation medium. 29132358 5 60 theme citric 1099:1104 arg1 metabolite 1126:1135 extracellular metabolite 1112:1135 extracellular metabolite 1112:1135 As a proof of concept, a high-throughput microcultivation of oleaginous filamentous fungi was conducted in order to monitor production of citric acid (extracellular metabolite) and triglyceride lipids (intracellular metabolites), as well as consumption of glucose in the cultivation medium. 29132358 2 61 theme bioprocesses 525:536 arg1 screening 502:510 high-throughput screening 486:510 high-throughput screening of microbial bioprocesses 486:536 We have assessed Fourier transform infrared spectroscopy (FTIR), in combination with high throughput micro-bioreactors and multivariate statistical analyses, for analysis of metabolites in high-throughput screening of microbial bioprocesses. 29132358 10 62 dep CONCLUSIONS 1920:1930 arg1 demonstrated 1946:1957 demonstrated 1946:1957 has demonstrated that intra- and extracellular metabolites, as well as nutrients in the cultivation medium, can be monitored by a unified approach by HTS FTIR 1942:2099 CONCLUSIONS The study has demonstrated that intra- and extracellular metabolites, as well as nutrients in the cultivation medium, can be monitored by a unified approach by HTS FTIR. 29132358 8 63 theme FTIR 1636:1639 arg1 data 1650:1653 the corresponding FTIR spectral data 1618:1653 the corresponding FTIR spectral data 1618:1653 Partial least square regression (PLSR) between HPLC glucose and citric acid data and the corresponding FTIR spectral data was used to set up calibration models. 29132358 1 64 theme high-throughput 244:258 arg1 screening 260:268 high-throughput screening 244:268 high-throughput screening of microbial bioprocesses 244:294 BACKGROUND Analyses of substrate and metabolites are often bottleneck activities in high-throughput screening of microbial bioprocesses. 29132358 2 65 from analysis 459:466 arg1 screening 502:510 high-throughput screening 486:510 high-throughput screening of microbial bioprocesses 486:536 We have assessed Fourier transform infrared spectroscopy (FTIR), in combination with high throughput micro-bioreactors and multivariate statistical analyses, for analysis of metabolites in high-throughput screening of microbial bioprocesses. 29132358 12 66 theme acids 2568:2572 arg1 production 2491:2500 production 2491:2500 production of single-cell proteins, biopolymers, polysaccharides, carboxylic acids, and other type of metabolites 2491:2603 It can be anticipated that the approach, demonstrated here on single-cell oil production by filamentous fungi, can find general application in screening studies of microbial bioprocesses, such as production of single-cell proteins, biopolymers, polysaccharides, carboxylic acids, and other type of metabolites. 29132358 12 67 theme single-cell 2505:2515 arg1 proteins 2517:2524 single-cell proteins 2505:2524 single-cell proteins 2505:2524 It can be anticipated that the approach, demonstrated here on single-cell oil production by filamentous fungi, can find general application in screening studies of microbial bioprocesses, such as production of single-cell proteins, biopolymers, polysaccharides, carboxylic acids, and other type of metabolites. 29132358 3 68 theme oleaginous 732:741 arg1 fungi 755:759 oleaginous filamentous fungi 732:759 oleaginous filamentous fungi 732:759 In our previous study, we have demonstrated that high-throughput (HTS) FTIR can be used for estimating content and composition of intracellular metabolites, namely triglyceride accumulation in oleaginous filamentous fungi. 29132358 11 69 theme Duetz 2178:2182 arg1 system 2201:2206 Duetz microtiter plate system 2178:2206 Duetz microtiter plate system 2178:2206 The proof-of-concept study has validated that HTS FTIR, in combination with Duetz microtiter plate system and chemometrics, can be used for high throughput screening of microbial bioprocesses. 29132358 2 70 from metabolites 471:481 arg1 screening 502:510 high-throughput screening 486:510 high-throughput screening of microbial bioprocesses 486:536 We have assessed Fourier transform infrared spectroscopy (FTIR), in combination with high throughput micro-bioreactors and multivariate statistical analyses, for analysis of metabolites in high-throughput screening of microbial bioprocesses. 29132358 0 71 from screening 123:131 arg1 analysis 55:62 simultaneous analysis 42:62 simultaneous analysis of intra- and extracellular metabolites in high-throughput screening of microbial bioprocesses 42:157 FTIR spectroscopy as a unified method for simultaneous analysis of intra- and extracellular metabolites in high-throughput screening of microbial bioprocesses. 29132358 2 72 theme throughput 387:396 arg1 micro-bioreactors 398:414 high throughput micro-bioreactors 382:414 high throughput micro-bioreactors 382:414 We have assessed Fourier transform infrared spectroscopy (FTIR), in combination with high throughput micro-bioreactors and multivariate statistical analyses, for analysis of metabolites in high-throughput screening of microbial bioprocesses. 29132358 1 73 theme bioprocesses 283:294 arg1 screening 260:268 high-throughput screening 244:268 high-throughput screening of microbial bioprocesses 244:294 BACKGROUND Analyses of substrate and metabolites are often bottleneck activities in high-throughput screening of microbial bioprocesses. 29132358 9 74 theme PLSR 1694:1697 arg1 results 1699:1705 PLSR results 1694:1705 PLSR results for HTS measurements 1694:1726 PLSR results for HTS measurements were very similar to the results obtained with ATR methodology, with high coefficients of determination (0.91-0.98) and low error values (4.9-8.6%) for both glucose and citric acid estimates. 29132358 9 75 theme acid 1904:1907 arg1 estimates 1909:1917 both glucose and citric acid estimates 1880:1917 both glucose and citric acid estimates 1880:1917 PLSR results for HTS measurements were very similar to the results obtained with ATR methodology, with high coefficients of determination (0.91-0.98) and low error values (4.9-8.6%) for both glucose and citric acid estimates. 29132358 3 76 theme HTS 605:607 arg1 FTIR 610:613 high-throughput (HTS) FTIR 588:613 high-throughput (HTS) FTIR 588:613 In our previous study, we have demonstrated that high-throughput (HTS) FTIR can be used for estimating content and composition of intracellular metabolites, namely triglyceride accumulation in oleaginous filamentous fungi. 29132358 12 77 theme general 2415:2421 arg1 application 2423:2433 general application 2415:2433 general application in screening studies of microbial bioprocesses, such as production of single-cell proteins, biopolymers, polysaccharides, carboxylic acids, and other type of metabolites 2415:2603 It can be anticipated that the approach, demonstrated here on single-cell oil production by filamentous fungi, can find general application in screening studies of microbial bioprocesses, such as production of single-cell proteins, biopolymers, polysaccharides, carboxylic acids, and other type of metabolites. 29132358 4 78 theme consumption 948:958 arg1 quantification 879:892 simultaneous quantification 866:892 simultaneous quantification of intra- and extracellular metabolites and substrate consumption 866:958 As a continuation of that research, in the present study HTS FTIR was evaluated as a unified method for simultaneous quantification of intra- and extracellular metabolites and substrate consumption. 29132358 7 79 theme liquid 1503:1508 arg1 HPLC 1526:1529 HPLC 1526:1529 HPLC 1526:1529 Glucose and citric acid content of growth media was quantified by high performance liquid chromatography (HPLC). 29132358 7 79 theme liquid 1503:1508 arg1 chromatography 1510:1523 high performance liquid chromatography 1486:1523 high performance liquid chromatography (HPLC) 1486:1530 Glucose and citric acid content of growth media was quantified by high performance liquid chromatography (HPLC). 29132358 8 80 theme calibration 1674:1684 arg1 models 1686:1691 calibration models 1674:1691 calibration models 1674:1691 Partial least square regression (PLSR) between HPLC glucose and citric acid data and the corresponding FTIR spectral data was used to set up calibration models. 29132358 6 81 theme reflection 1339:1348 arg1 method 1386:1391 an established method 1371:1391 an established method for bioprocess monitoring 1371:1417 RESULTS HTS FTIR analyses of supernatant samples was compared with an attenuated total reflection (ATR) FTIR, which is an established method for bioprocess monitoring. 29132358 6 81 theme reflection 1339:1348 arg1 FTIR 1356:1359 an attenuated total reflection (ATR) FTIR 1319:1359 an attenuated total reflection (ATR) FTIR 1319:1359 RESULTS HTS FTIR analyses of supernatant samples was compared with an attenuated total reflection (ATR) FTIR, which is an established method for bioprocess monitoring. 29132358 3 82 theme high-throughput 588:602 arg1 FTIR 610:613 high-throughput (HTS) FTIR 588:613 high-throughput (HTS) FTIR 588:613 In our previous study, we have demonstrated that high-throughput (HTS) FTIR can be used for estimating content and composition of intracellular metabolites, namely triglyceride accumulation in oleaginous filamentous fungi. 29132358 1 83 theme substrate 183:191 arg1 activities 230:239 bottleneck activities 219:239 bottleneck activities in high-throughput screening of microbial bioprocesses 219:294 BACKGROUND Analyses of substrate and metabolites are often bottleneck activities in high-throughput screening of microbial bioprocesses. 29132358 1 83 theme substrate 183:191 arg1 Analyses 171:178 BACKGROUND Analyses 160:178 BACKGROUND Analyses of substrate and metabolites 160:207 BACKGROUND Analyses of substrate and metabolites are often bottleneck activities in high-throughput screening of microbial bioprocesses. 29132358 11 84 theme microtiter 2184:2193 arg1 system 2201:2206 Duetz microtiter plate system 2178:2206 Duetz microtiter plate system 2178:2206 The proof-of-concept study has validated that HTS FTIR, in combination with Duetz microtiter plate system and chemometrics, can be used for high throughput screening of microbial bioprocesses. 29132358 4 85 theme intra- 897:902 arg1 metabolites 922:932 intra- and extracellular metabolites 897:932 intra- and extracellular metabolites 897:932 As a continuation of that research, in the present study HTS FTIR was evaluated as a unified method for simultaneous quantification of intra- and extracellular metabolites and substrate consumption. 29132358 7 86 theme high 1486:1489 arg1 HPLC 1526:1529 HPLC 1526:1529 HPLC 1526:1529 Glucose and citric acid content of growth media was quantified by high performance liquid chromatography (HPLC). 29132358 7 86 theme high 1486:1489 arg1 chromatography 1510:1523 high performance liquid chromatography 1486:1523 high performance liquid chromatography (HPLC) 1486:1530 Glucose and citric acid content of growth media was quantified by high performance liquid chromatography (HPLC). 29132358 11 87 theme throughput 2247:2256 arg1 screening 2258:2266 high throughput screening 2242:2266 high throughput screening of microbial bioprocesses 2242:2292 The proof-of-concept study has validated that HTS FTIR, in combination with Duetz microtiter plate system and chemometrics, can be used for high throughput screening of microbial bioprocesses. 29132358 6 88 theme attenuated 1322:1331 arg1 method 1386:1391 an established method 1371:1391 an established method for bioprocess monitoring 1371:1417 RESULTS HTS FTIR analyses of supernatant samples was compared with an attenuated total reflection (ATR) FTIR, which is an established method for bioprocess monitoring. 29132358 6 88 theme attenuated 1322:1331 arg1 FTIR 1356:1359 an attenuated total reflection (ATR) FTIR 1319:1359 an attenuated total reflection (ATR) FTIR 1319:1359 RESULTS HTS FTIR analyses of supernatant samples was compared with an attenuated total reflection (ATR) FTIR, which is an established method for bioprocess monitoring. 29132358 1 89 theme metabolites 197:207 arg1 activities 230:239 bottleneck activities 219:239 bottleneck activities in high-throughput screening of microbial bioprocesses 219:294 BACKGROUND Analyses of substrate and metabolites are often bottleneck activities in high-throughput screening of microbial bioprocesses. 29132358 1 89 theme metabolites 197:207 arg1 Analyses 171:178 BACKGROUND Analyses 160:178 BACKGROUND Analyses of substrate and metabolites 160:207 BACKGROUND Analyses of substrate and metabolites are often bottleneck activities in high-throughput screening of microbial bioprocesses. 29132358 4 90 theme extracellular 908:920 arg1 metabolites 922:932 intra- and extracellular metabolites 897:932 intra- and extracellular metabolites 897:932 As a continuation of that research, in the present study HTS FTIR was evaluated as a unified method for simultaneous quantification of intra- and extracellular metabolites and substrate consumption. 29132358 12 91 theme bioprocesses 2469:2480 arg1 studies 2448:2454 screening studies 2438:2454 screening studies of microbial bioprocesses, such as production of single-cell proteins, biopolymers, polysaccharides, carboxylic acids, and other type of metabolites 2438:2603 It can be anticipated that the approach, demonstrated here on single-cell oil production by filamentous fungi, can find general application in screening studies of microbial bioprocesses, such as production of single-cell proteins, biopolymers, polysaccharides, carboxylic acids, and other type of metabolites. 29132358 6 92 theme bioprocess 1397:1406 arg1 monitoring 1408:1417 bioprocess monitoring 1397:1417 bioprocess monitoring 1397:1417 RESULTS HTS FTIR analyses of supernatant samples was compared with an attenuated total reflection (ATR) FTIR, which is an established method for bioprocess monitoring. 29132358 3 93 theme metabolites 683:693 arg1 content 642:648 content 642:648 content 642:648 In our previous study, we have demonstrated that high-throughput (HTS) FTIR can be used for estimating content and composition of intracellular metabolites, namely triglyceride accumulation in oleaginous filamentous fungi. 29132358 3 93 theme metabolites 683:693 arg1 composition 654:664 composition 654:664 composition 654:664 In our previous study, we have demonstrated that high-throughput (HTS) FTIR can be used for estimating content and composition of intracellular metabolites, namely triglyceride accumulation in oleaginous filamentous fungi. 29132358 7 94 theme media 1462:1466 arg1 content 1444:1450 Glucose and citric acid content 1420:1450 Glucose and citric acid content of growth media 1420:1466 Glucose and citric acid content of growth media was quantified by high performance liquid chromatography (HPLC). 29132358 11 95 theme bioprocesses 2281:2292 arg1 screening 2258:2266 high throughput screening 2242:2266 high throughput screening of microbial bioprocesses 2242:2292 The proof-of-concept study has validated that HTS FTIR, in combination with Duetz microtiter plate system and chemometrics, can be used for high throughput screening of microbial bioprocesses. 29132358 0 96 theme bioprocesses 146:157 arg1 screening 123:131 high-throughput screening 107:131 high-throughput screening of microbial bioprocesses 107:157 FTIR spectroscopy as a unified method for simultaneous analysis of intra- and extracellular metabolites in high-throughput screening of microbial bioprocesses. 29132358 5 97 theme lipids 1155:1160 arg1 production 1085:1094 production 1085:1094 production of citric acid (extracellular metabolite) and triglyceride lipids (intracellular metabolites) 1085:1188 As a proof of concept, a high-throughput microcultivation of oleaginous filamentous fungi was conducted in order to monitor production of citric acid (extracellular metabolite) and triglyceride lipids (intracellular metabolites), as well as consumption of glucose in the cultivation medium. 29132358 5 97 theme lipids 1155:1160 arg1 consumption 1202:1212 consumption 1202:1212 consumption of glucose 1202:1223 As a proof of concept, a high-throughput microcultivation of oleaginous filamentous fungi was conducted in order to monitor production of citric acid (extracellular metabolite) and triglyceride lipids (intracellular metabolites), as well as consumption of glucose in the cultivation medium. 29132358 6 98 dep RESULTS 1252:1258 arg1 compared 1305:1312 compared 1305:1312 was compared with an attenuated total reflection (ATR) FTIR, which is an established method for bioprocess monitoring 1301:1417 RESULTS HTS FTIR analyses of supernatant samples was compared with an attenuated total reflection (ATR) FTIR, which is an established method for bioprocess monitoring. 29132358 12 99 from application 2423:2433 arg1 studies 2448:2454 screening studies 2438:2454 screening studies of microbial bioprocesses, such as production of single-cell proteins, biopolymers, polysaccharides, carboxylic acids, and other type of metabolites 2438:2603 It can be anticipated that the approach, demonstrated here on single-cell oil production by filamentous fungi, can find general application in screening studies of microbial bioprocesses, such as production of single-cell proteins, biopolymers, polysaccharides, carboxylic acids, and other type of metabolites. 29132358 5 100 theme intracellular 1163:1175 arg1 metabolites 1177:1187 intracellular metabolites 1163:1187 intracellular metabolites 1163:1187 As a proof of concept, a high-throughput microcultivation of oleaginous filamentous fungi was conducted in order to monitor production of citric acid (extracellular metabolite) and triglyceride lipids (intracellular metabolites), as well as consumption of glucose in the cultivation medium. 29132358 5 101 theme concept 975:981 arg1 proof 966:970 a proof 964:970 a proof of concept 964:981 As a proof of concept, a high-throughput microcultivation of oleaginous filamentous fungi was conducted in order to monitor production of citric acid (extracellular metabolite) and triglyceride lipids (intracellular metabolites), as well as consumption of glucose in the cultivation medium. 29132358 5 101 theme concept 975:981 arg1 microcultivation 1002:1017 a high-throughput microcultivation 984:1017 a high-throughput microcultivation of oleaginous filamentous fungi 984:1049 As a proof of concept, a high-throughput microcultivation of oleaginous filamentous fungi was conducted in order to monitor production of citric acid (extracellular metabolite) and triglyceride lipids (intracellular metabolites), as well as consumption of glucose in the cultivation medium. 29132358 8 102 theme Partial 1533:1539 arg1 PLSR 1566:1569 PLSR 1566:1569 PLSR 1566:1569 Partial least square regression (PLSR) between HPLC glucose and citric acid data and the corresponding FTIR spectral data was used to set up calibration models. 29132358 8 102 theme Partial 1533:1539 arg1 regression 1554:1563 Partial least square regression 1533:1563 Partial least square regression (PLSR) between HPLC glucose and citric acid data and the corresponding FTIR spectral data 1533:1653 Partial least square regression (PLSR) between HPLC glucose and citric acid data and the corresponding FTIR spectral data was used to set up calibration models. 29132358 6 103 theme samples 1293:1299 arg1 analyses 1269:1276 HTS FTIR analyses 1260:1276 HTS FTIR analyses of supernatant samples 1260:1299 RESULTS HTS FTIR analyses of supernatant samples was compared with an attenuated total reflection (ATR) FTIR, which is an established method for bioprocess monitoring. 29132358 3 104 theme intracellular 669:681 arg1 metabolites 683:693 intracellular metabolites 669:693 intracellular metabolites 669:693 In our previous study, we have demonstrated that high-throughput (HTS) FTIR can be used for estimating content and composition of intracellular metabolites, namely triglyceride accumulation in oleaginous filamentous fungi. 29132358 11 105 with combination 2161:2171 arg1 chemometrics 2212:2223 chemometrics 2212:2223 chemometrics 2212:2223 The proof-of-concept study has validated that HTS FTIR, in combination with Duetz microtiter plate system and chemometrics, can be used for high throughput screening of microbial bioprocesses. 29132358 11 105 with combination 2161:2171 arg1 system 2201:2206 Duetz microtiter plate system 2178:2206 Duetz microtiter plate system 2178:2206 The proof-of-concept study has validated that HTS FTIR, in combination with Duetz microtiter plate system and chemometrics, can be used for high throughput screening of microbial bioprocesses. 29132358 0 106 from metabolites 92:102 arg1 screening 123:131 high-throughput screening 107:131 high-throughput screening of microbial bioprocesses 107:157 FTIR spectroscopy as a unified method for simultaneous analysis of intra- and extracellular metabolites in high-throughput screening of microbial bioprocesses. 29132358 4 107 theme research 788:795 arg1 FTIR 823:826 HTS FTIR 819:826 HTS FTIR 819:826 As a continuation of that research, in the present study HTS FTIR was evaluated as a unified method for simultaneous quantification of intra- and extracellular metabolites and substrate consumption. 29132358 4 107 theme research 788:795 arg1 continuation 767:778 a continuation 765:778 a continuation of that research 765:795 As a continuation of that research, in the present study HTS FTIR was evaluated as a unified method for simultaneous quantification of intra- and extracellular metabolites and substrate consumption. 29132358 10 108 theme cultivation 2030:2040 arg1 medium 2042:2047 the cultivation medium 2026:2047 the cultivation medium 2026:2047 CONCLUSIONS The study has demonstrated that intra- and extracellular metabolites, as well as nutrients in the cultivation medium, can be monitored by a unified approach by HTS FTIR. 29132358 12 109 theme polysaccharides 2540:2554 arg1 production 2491:2500 production 2491:2500 production of single-cell proteins, biopolymers, polysaccharides, carboxylic acids, and other type of metabolites 2491:2603 It can be anticipated that the approach, demonstrated here on single-cell oil production by filamentous fungi, can find general application in screening studies of microbial bioprocesses, such as production of single-cell proteins, biopolymers, polysaccharides, carboxylic acids, and other type of metabolites. 29132358 6 110 theme FTIR 1264:1267 arg1 analyses 1269:1276 HTS FTIR analyses 1260:1276 HTS FTIR analyses of supernatant samples 1260:1299 RESULTS HTS FTIR analyses of supernatant samples was compared with an attenuated total reflection (ATR) FTIR, which is an established method for bioprocess monitoring. 29132358 12 111 theme filamentous 2387:2397 arg1 fungi 2399:2403 filamentous fungi 2387:2403 filamentous fungi 2387:2403 It can be anticipated that the approach, demonstrated here on single-cell oil production by filamentous fungi, can find general application in screening studies of microbial bioprocesses, such as production of single-cell proteins, biopolymers, polysaccharides, carboxylic acids, and other type of metabolites. 29132358 11 112 theme high 2242:2245 arg1 screening 2258:2266 high throughput screening 2242:2266 high throughput screening of microbial bioprocesses 2242:2292 The proof-of-concept study has validated that HTS FTIR, in combination with Duetz microtiter plate system and chemometrics, can be used for high throughput screening of microbial bioprocesses. 29132358 12 113 theme metabolites 2593:2603 arg1 biopolymers 2527:2537 biopolymers 2527:2537 biopolymers 2527:2537 It can be anticipated that the approach, demonstrated here on single-cell oil production by filamentous fungi, can find general application in screening studies of microbial bioprocesses, such as production of single-cell proteins, biopolymers, polysaccharides, carboxylic acids, and other type of metabolites. 29132358 12 113 theme metabolites 2593:2603 arg1 proteins 2517:2524 single-cell proteins 2505:2524 single-cell proteins 2505:2524 It can be anticipated that the approach, demonstrated here on single-cell oil production by filamentous fungi, can find general application in screening studies of microbial bioprocesses, such as production of single-cell proteins, biopolymers, polysaccharides, carboxylic acids, and other type of metabolites. 29132358 12 113 theme metabolites 2593:2603 arg1 type 2585:2588 other type 2579:2588 other type of metabolites 2579:2603 It can be anticipated that the approach, demonstrated here on single-cell oil production by filamentous fungi, can find general application in screening studies of microbial bioprocesses, such as production of single-cell proteins, biopolymers, polysaccharides, carboxylic acids, and other type of metabolites. 29132358 12 113 theme metabolites 2593:2603 arg1 polysaccharides 2540:2554 polysaccharides 2540:2554 polysaccharides 2540:2554 It can be anticipated that the approach, demonstrated here on single-cell oil production by filamentous fungi, can find general application in screening studies of microbial bioprocesses, such as production of single-cell proteins, biopolymers, polysaccharides, carboxylic acids, and other type of metabolites. 29132358 12 113 theme metabolites 2593:2603 arg1 acids 2568:2572 carboxylic acids 2557:2572 carboxylic acids 2557:2572 It can be anticipated that the approach, demonstrated here on single-cell oil production by filamentous fungi, can find general application in screening studies of microbial bioprocesses, such as production of single-cell proteins, biopolymers, polysaccharides, carboxylic acids, and other type of metabolites. 29132358 2 114 dep transform 322:330 arg1 infrared 332:339 infrared 332:339 infrared 332:339 We have assessed Fourier transform infrared spectroscopy (FTIR), in combination with high throughput micro-bioreactors and multivariate statistical analyses, for analysis of metabolites in high-throughput screening of microbial bioprocesses. 29132358 0 115 theme metabolites 92:102 arg1 analysis 55:62 simultaneous analysis 42:62 simultaneous analysis of intra- and extracellular metabolites in high-throughput screening of microbial bioprocesses 42:157 FTIR spectroscopy as a unified method for simultaneous analysis of intra- and extracellular metabolites in high-throughput screening of microbial bioprocesses. 29132358 5 116 theme fungi 1045:1049 arg1 proof 966:970 a proof 964:970 a proof of concept 964:981 As a proof of concept, a high-throughput microcultivation of oleaginous filamentous fungi was conducted in order to monitor production of citric acid (extracellular metabolite) and triglyceride lipids (intracellular metabolites), as well as consumption of glucose in the cultivation medium. 29132358 5 116 theme fungi 1045:1049 arg1 microcultivation 1002:1017 a high-throughput microcultivation 984:1017 a high-throughput microcultivation of oleaginous filamentous fungi 984:1049 As a proof of concept, a high-throughput microcultivation of oleaginous filamentous fungi was conducted in order to monitor production of citric acid (extracellular metabolite) and triglyceride lipids (intracellular metabolites), as well as consumption of glucose in the cultivation medium. 29132358 9 117 theme determination 1818:1830 arg1 coefficients 1802:1813 high coefficients 1797:1813 high coefficients of determination (0.91-0.98) 1797:1842 PLSR results for HTS measurements were very similar to the results obtained with ATR methodology, with high coefficients of determination (0.91-0.98) and low error values (4.9-8.6%) for both glucose and citric acid estimates. 29132358 9 117 theme determination 1818:1830 arg1 values 1858:1863 low error values 1848:1863 low error values (4.9-8.6%) 1848:1874 PLSR results for HTS measurements were very similar to the results obtained with ATR methodology, with high coefficients of determination (0.91-0.98) and low error values (4.9-8.6%) for both glucose and citric acid estimates. 29132358 9 117 theme determination 1818:1830 arg1 % 1873:1873 4.9-8.6% 1866:1873 4.9-8.6% 1866:1873 PLSR results for HTS measurements were very similar to the results obtained with ATR methodology, with high coefficients of determination (0.91-0.98) and low error values (4.9-8.6%) for both glucose and citric acid estimates. 29132358 8 118 theme HPLC 1580:1583 arg1 glucose 1585:1591 HPLC glucose 1580:1591 HPLC glucose 1580:1591 Partial least square regression (PLSR) between HPLC glucose and citric acid data and the corresponding FTIR spectral data was used to set up calibration models. 29132358 4 119 theme HTS 819:821 arg1 FTIR 823:826 HTS FTIR 819:826 HTS FTIR 819:826 As a continuation of that research, in the present study HTS FTIR was evaluated as a unified method for simultaneous quantification of intra- and extracellular metabolites and substrate consumption. 29132358 4 119 theme HTS 819:821 arg1 continuation 767:778 a continuation 765:778 a continuation of that research 765:795 As a continuation of that research, in the present study HTS FTIR was evaluated as a unified method for simultaneous quantification of intra- and extracellular metabolites and substrate consumption. 29132358 4 119 theme HTS 819:821 arg1 method 855:860 a unified method 845:860 a unified method for simultaneous quantification of intra- and extracellular metabolites and substrate consumption 845:958 As a continuation of that research, in the present study HTS FTIR was evaluated as a unified method for simultaneous quantification of intra- and extracellular metabolites and substrate consumption. 29132358 0 120 theme high-throughput 107:121 arg1 screening 123:131 high-throughput screening 107:131 high-throughput screening of microbial bioprocesses 107:157 FTIR spectroscopy as a unified method for simultaneous analysis of intra- and extracellular metabolites in high-throughput screening of microbial bioprocesses. 29132358 10 121 from nutrients 2013:2021 arg1 medium 2042:2047 the cultivation medium 2026:2047 the cultivation medium 2026:2047 CONCLUSIONS The study has demonstrated that intra- and extracellular metabolites, as well as nutrients in the cultivation medium, can be monitored by a unified approach by HTS FTIR. 29132358 8 122 theme acid 1604:1607 arg1 data 1609:1612 HPLC glucose and citric acid data 1580:1612 HPLC glucose and citric acid data 1580:1612 Partial least square regression (PLSR) between HPLC glucose and citric acid data and the corresponding FTIR spectral data was used to set up calibration models. 29132358 12 123 theme type 2585:2588 arg1 production 2491:2500 production 2491:2500 production of single-cell proteins, biopolymers, polysaccharides, carboxylic acids, and other type of metabolites 2491:2603 It can be anticipated that the approach, demonstrated here on single-cell oil production by filamentous fungi, can find general application in screening studies of microbial bioprocesses, such as production of single-cell proteins, biopolymers, polysaccharides, carboxylic acids, and other type of metabolites. 29132358 2 124 theme multivariate 420:431 arg1 analyses 445:452 multivariate statistical analyses 420:452 multivariate statistical analyses 420:452 We have assessed Fourier transform infrared spectroscopy (FTIR), in combination with high throughput micro-bioreactors and multivariate statistical analyses, for analysis of metabolites in high-throughput screening of microbial bioprocesses. 29132358 5 125 theme oleaginous 1022:1031 arg1 fungi 1045:1049 oleaginous filamentous fungi 1022:1049 oleaginous filamentous fungi 1022:1049 As a proof of concept, a high-throughput microcultivation of oleaginous filamentous fungi was conducted in order to monitor production of citric acid (extracellular metabolite) and triglyceride lipids (intracellular metabolites), as well as consumption of glucose in the cultivation medium. 29132358 9 126 theme error 1852:1856 arg1 values 1858:1863 low error values 1848:1863 low error values (4.9-8.6%) 1848:1874 PLSR results for HTS measurements were very similar to the results obtained with ATR methodology, with high coefficients of determination (0.91-0.98) and low error values (4.9-8.6%) for both glucose and citric acid estimates. 29132358 9 126 theme error 1852:1856 arg1 % 1873:1873 4.9-8.6% 1866:1873 4.9-8.6% 1866:1873 PLSR results for HTS measurements were very similar to the results obtained with ATR methodology, with high coefficients of determination (0.91-0.98) and low error values (4.9-8.6%) for both glucose and citric acid estimates. 29132358 3 127 theme triglyceride 703:714 arg1 accumulation 716:727 triglyceride accumulation 703:727 triglyceride accumulation in oleaginous filamentous fungi 703:759 In our previous study, we have demonstrated that high-throughput (HTS) FTIR can be used for estimating content and composition of intracellular metabolites, namely triglyceride accumulation in oleaginous filamentous fungi. 29132358 4 128 theme present 805:811 arg1 study 813:817 the present study 801:817 the present study 801:817 As a continuation of that research, in the present study HTS FTIR was evaluated as a unified method for simultaneous quantification of intra- and extracellular metabolites and substrate consumption. 29132358 12 129 theme carboxylic 2557:2566 arg1 acids 2568:2572 carboxylic acids 2557:2572 carboxylic acids 2557:2572 It can be anticipated that the approach, demonstrated here on single-cell oil production by filamentous fungi, can find general application in screening studies of microbial bioprocesses, such as production of single-cell proteins, biopolymers, polysaccharides, carboxylic acids, and other type of metabolites. 29132358 8 130 theme corresponding 1622:1634 arg1 data 1650:1653 the corresponding FTIR spectral data 1618:1653 the corresponding FTIR spectral data 1618:1653 Partial least square regression (PLSR) between HPLC glucose and citric acid data and the corresponding FTIR spectral data was used to set up calibration models. 29132358 0 131 theme simultaneous 42:53 arg1 analysis 55:62 simultaneous analysis 42:62 simultaneous analysis of intra- and extracellular metabolites in high-throughput screening of microbial bioprocesses 42:157 FTIR spectroscopy as a unified method for simultaneous analysis of intra- and extracellular metabolites in high-throughput screening of microbial bioprocesses. 29132358 2 132 with combination 365:375 arg1 analyses 445:452 multivariate statistical analyses 420:452 multivariate statistical analyses 420:452 We have assessed Fourier transform infrared spectroscopy (FTIR), in combination with high throughput micro-bioreactors and multivariate statistical analyses, for analysis of metabolites in high-throughput screening of microbial bioprocesses. 29132358 2 132 with combination 365:375 arg1 micro-bioreactors 398:414 high throughput micro-bioreactors 382:414 high throughput micro-bioreactors 382:414 We have assessed Fourier transform infrared spectroscopy (FTIR), in combination with high throughput micro-bioreactors and multivariate statistical analyses, for analysis of metabolites in high-throughput screening of microbial bioprocesses. 29132358 5 133 theme acid 1106:1109 arg1 production 1085:1094 production 1085:1094 production of citric acid (extracellular metabolite) and triglyceride lipids (intracellular metabolites) 1085:1188 As a proof of concept, a high-throughput microcultivation of oleaginous filamentous fungi was conducted in order to monitor production of citric acid (extracellular metabolite) and triglyceride lipids (intracellular metabolites), as well as consumption of glucose in the cultivation medium. 29132358 5 133 theme acid 1106:1109 arg1 consumption 1202:1212 consumption 1202:1212 consumption of glucose 1202:1223 As a proof of concept, a high-throughput microcultivation of oleaginous filamentous fungi was conducted in order to monitor production of citric acid (extracellular metabolite) and triglyceride lipids (intracellular metabolites), as well as consumption of glucose in the cultivation medium. 29132358 2 134 theme microbial 515:523 arg1 bioprocesses 525:536 microbial bioprocesses 515:536 microbial bioprocesses 515:536 We have assessed Fourier transform infrared spectroscopy (FTIR), in combination with high throughput micro-bioreactors and multivariate statistical analyses, for analysis of metabolites in high-throughput screening of microbial bioprocesses. 29132358 8 135 theme spectral 1641:1648 arg1 data 1650:1653 the corresponding FTIR spectral data 1618:1653 the corresponding FTIR spectral data 1618:1653 Partial least square regression (PLSR) between HPLC glucose and citric acid data and the corresponding FTIR spectral data was used to set up calibration models. 29132358 3 136 theme filamentous 743:753 arg1 fungi 755:759 oleaginous filamentous fungi 732:759 oleaginous filamentous fungi 732:759 In our previous study, we have demonstrated that high-throughput (HTS) FTIR can be used for estimating content and composition of intracellular metabolites, namely triglyceride accumulation in oleaginous filamentous fungi. 29132358 5 137 theme cultivation 1232:1242 arg1 medium 1244:1249 the cultivation medium 1228:1249 the cultivation medium 1228:1249 As a proof of concept, a high-throughput microcultivation of oleaginous filamentous fungi was conducted in order to monitor production of citric acid (extracellular metabolite) and triglyceride lipids (intracellular metabolites), as well as consumption of glucose in the cultivation medium. 29132358 10 138 theme unified 2072:2078 arg1 approach 2080:2087 a unified approach 2070:2087 a unified approach by HTS FTIR 2070:2099 CONCLUSIONS The study has demonstrated that intra- and extracellular metabolites, as well as nutrients in the cultivation medium, can be monitored by a unified approach by HTS FTIR. 29132358 6 139 theme established 1374:1384 arg1 method 1386:1391 an established method 1371:1391 an established method for bioprocess monitoring 1371:1417 RESULTS HTS FTIR analyses of supernatant samples was compared with an attenuated total reflection (ATR) FTIR, which is an established method for bioprocess monitoring. 29132358 6 139 theme established 1374:1384 arg1 FTIR 1356:1359 an attenuated total reflection (ATR) FTIR 1319:1359 an attenuated total reflection (ATR) FTIR 1319:1359 RESULTS HTS FTIR analyses of supernatant samples was compared with an attenuated total reflection (ATR) FTIR, which is an established method for bioprocess monitoring. 29132358 3 140 theme previous 546:553 arg1 study 555:559 our previous study 542:559 our previous study 542:559 In our previous study, we have demonstrated that high-throughput (HTS) FTIR can be used for estimating content and composition of intracellular metabolites, namely triglyceride accumulation in oleaginous filamentous fungi. 29132358 0 141 dep spectroscopy 5:16 arg1 method 31:36 a unified method 21:36 a unified method for simultaneous analysis of intra- and extracellular metabolites in high-throughput screening of microbial bioprocesses 21:157 FTIR spectroscopy as a unified method for simultaneous analysis of intra- and extracellular metabolites in high-throughput screening of microbial bioprocesses. 29132358 9 142 theme glucose 1885:1891 arg1 estimates 1909:1917 both glucose and citric acid estimates 1880:1917 both glucose and citric acid estimates 1880:1917 PLSR results for HTS measurements were very similar to the results obtained with ATR methodology, with high coefficients of determination (0.91-0.98) and low error values (4.9-8.6%) for both glucose and citric acid estimates. 29132358 8 143 used used 1659:1662 arg2 regression 1554:1563 Partial least square regression 1533:1563 Partial least square regression (PLSR) between HPLC glucose and citric acid data and the corresponding FTIR spectral data 1533:1653 Partial least square regression (PLSR) between HPLC glucose and citric acid data and the corresponding FTIR spectral data was used to set up calibration models. 29132358 8 143 used used 1659:1662 arg2 PLSR 1566:1569 PLSR 1566:1569 PLSR 1566:1569 Partial least square regression (PLSR) between HPLC glucose and citric acid data and the corresponding FTIR spectral data was used to set up calibration models. 29132358 4 144 theme unified 847:853 arg1 FTIR 823:826 HTS FTIR 819:826 HTS FTIR 819:826 As a continuation of that research, in the present study HTS FTIR was evaluated as a unified method for simultaneous quantification of intra- and extracellular metabolites and substrate consumption. 29132358 4 144 theme unified 847:853 arg1 method 855:860 a unified method 845:860 a unified method for simultaneous quantification of intra- and extracellular metabolites and substrate consumption 845:958 As a continuation of that research, in the present study HTS FTIR was evaluated as a unified method for simultaneous quantification of intra- and extracellular metabolites and substrate consumption. 29132358 1 145 theme microbial 273:281 arg1 bioprocesses 283:294 microbial bioprocesses 273:294 microbial bioprocesses 273:294 BACKGROUND Analyses of substrate and metabolites are often bottleneck activities in high-throughput screening of microbial bioprocesses. 28586386 7 0 theme different 1889:1897 arg1 response 1899:1906 a different response 1887:1906 a different response of adaptive immunity 1887:1927 Altogether, present results suggest that CG258-KP of the two clades are capable of inducing a different response of adaptive immunity in the human host. 28586386 5 1 theme HLA-DR 1300:1305 arg1 expression 1277:1286 the bacteria-induced expression 1256:1286 the bacteria-induced expression of CD86 and HLA-DR by monocytes and myeloid dendritic cells 1256:1346 While no differences in the rate of bacterial internalization or in the bacteria-induced expression of CD86 and HLA-DR by monocytes and myeloid dendritic cells were revealed, we found that the two strains significantly differ in inducing the production of cytokines involved in the adaptive immune response, as IL-1β, IL-23 and TNF-α, by antigen-presenting cells, with KKBO-1 being a more efficient inducer than KK207-1. 28586386 3 2 theme PBMC 887:890 arg1 vivo-stimulation 867:882 ex vivo-stimulation 864:882 ex vivo-stimulation of PBMC from normal donors 864:909 In this paper, we investigated the ability of two ST258-KP strains, KKBO-1 and KK207-1, selected as representatives of ST258-KP clade 2 and clade 1, respectively, to activate an adaptive immune response using ex vivo-stimulation of PBMC from normal donors as an experimental model. 28586386 3 2 theme PBMC 887:890 arg1 model 930:934 an experimental model 914:934 an experimental model 914:934 In this paper, we investigated the ability of two ST258-KP strains, KKBO-1 and KK207-1, selected as representatives of ST258-KP clade 2 and clade 1, respectively, to activate an adaptive immune response using ex vivo-stimulation of PBMC from normal donors as an experimental model. 28586386 6 3 theme immune-inflammatory 1764:1782 arg1 responses 1784:1792 immune-inflammatory responses 1764:1792 immune-inflammatory responses 1764:1792 The immune responses elicited by KK207-1 were comparable to those elicited by CIP 52.145, a highly virulent K. pneumoniae reference strain known to escape immune-inflammatory responses. 28586386 6 4 theme K. 1717:1718 arg1 strain 1741:1746 a highly virulent K. pneumoniae reference strain 1699:1746 a highly virulent K. pneumoniae reference strain known to escape immune-inflammatory responses 1699:1792 The immune responses elicited by KK207-1 were comparable to those elicited by CIP 52.145, a highly virulent K. pneumoniae reference strain known to escape immune-inflammatory responses. 28586386 6 4 theme K. 1717:1718 arg1 52.145 1691:1696 CIP 52.145 1687:1696 CIP 52.145 1687:1696 The immune responses elicited by KK207-1 were comparable to those elicited by CIP 52.145, a highly virulent K. pneumoniae reference strain known to escape immune-inflammatory responses. 28586386 0 5 theme pandemic 60:67 arg1 lineages 104:111 the pandemic ST258 Klebsiella pneumoniae clonal lineages 56:111 the pandemic ST258 Klebsiella pneumoniae clonal lineages producing KPC-type carbapenemase 56:144 Differential Th17 response induced by the two clades of the pandemic ST258 Klebsiella pneumoniae clonal lineages producing KPC-type carbapenemase. 28586386 1 6 theme sequence 322:329 arg1 type 331:334 sequence type (ST) 258 322:343 sequence type (ST) 258 322:343 The spread of KPC-type carbapenemases is mainly attributed to the global dissemination of Klebsiella pneumoniae (KP) strains belonging to the clonal group (CG) 258, including sequence type (ST) 258 and other related STs. 28586386 2 7 theme fragment 596:603 arg1 recombination 569:581 recombination 569:581 recombination of a genomic fragment carrying the capsular polysaccharide (cps) locus 569:652 Two distinct clades of CG258-KP have evolved, which differ mainly for the composition of their capsular polysaccharides, and recent studies indicate that clade 1 evolved from an ancestor of clade 2 by recombination of a genomic fragment carrying the capsular polysaccharide (cps) locus. 28586386 1 8 theme KPC-type 161:168 arg1 carbapenemases 170:183 KPC-type carbapenemases 161:183 KPC-type carbapenemases 161:183 The spread of KPC-type carbapenemases is mainly attributed to the global dissemination of Klebsiella pneumoniae (KP) strains belonging to the clonal group (CG) 258, including sequence type (ST) 258 and other related STs. 28586386 7 9 theme present 1807:1813 arg1 results 1815:1821 present results 1807:1821 present results 1807:1821 Altogether, present results suggest that CG258-KP of the two clades are capable of inducing a different response of adaptive immunity in the human host. 28586386 4 10 theme cells 1068:1072 arg1 percentage 1044:1053 the percentage 1040:1053 the percentage of CD4+IL17+ cells 1040:1072 Our data showed that KKBO-1 (clade 2) induces a Th17 response more efficiently than KK207-1 (clade 1): the percentage of CD4+IL17+ cells and the production of IL-17A were significantly higher in cultures with KKBO-1 compared to cultures with KK207-1. 28586386 4 10 theme cells 1068:1072 arg1 higher 1122:1127 higher 1122:1127 higher 1122:1127 Our data showed that KKBO-1 (clade 2) induces a Th17 response more efficiently than KK207-1 (clade 1): the percentage of CD4+IL17+ cells and the production of IL-17A were significantly higher in cultures with KKBO-1 compared to cultures with KK207-1. 28586386 4 10 theme cells 1068:1072 arg1 production 1082:1091 the production 1078:1091 the production of IL-17A 1078:1101 Our data showed that KKBO-1 (clade 2) induces a Th17 response more efficiently than KK207-1 (clade 1): the percentage of CD4+IL17+ cells and the production of IL-17A were significantly higher in cultures with KKBO-1 compared to cultures with KK207-1. 28586386 2 11 theme genomic 588:594 arg1 fragment 596:603 a genomic fragment 586:603 a genomic fragment carrying the capsular polysaccharide (cps) locus 586:652 Two distinct clades of CG258-KP have evolved, which differ mainly for the composition of their capsular polysaccharides, and recent studies indicate that clade 1 evolved from an ancestor of clade 2 by recombination of a genomic fragment carrying the capsular polysaccharide (cps) locus. 28586386 5 12 theme internalization 1234:1248 arg1 rate 1216:1219 the rate 1212:1219 the rate of bacterial internalization 1212:1248 While no differences in the rate of bacterial internalization or in the bacteria-induced expression of CD86 and HLA-DR by monocytes and myeloid dendritic cells were revealed, we found that the two strains significantly differ in inducing the production of cytokines involved in the adaptive immune response, as IL-1β, IL-23 and TNF-α, by antigen-presenting cells, with KKBO-1 being a more efficient inducer than KK207-1. 28586386 1 13 theme strains 264:270 arg1 dissemination 220:232 the global dissemination 209:232 the global dissemination of Klebsiella pneumoniae (KP) strains belonging to the clonal group (CG) 258, including sequence type (ST) 258 and other related STs 209:365 The spread of KPC-type carbapenemases is mainly attributed to the global dissemination of Klebsiella pneumoniae (KP) strains belonging to the clonal group (CG) 258, including sequence type (ST) 258 and other related STs. 28586386 0 14 theme Klebsiella 75:84 arg1 lineages 104:111 the pandemic ST258 Klebsiella pneumoniae clonal lineages 56:111 the pandemic ST258 Klebsiella pneumoniae clonal lineages producing KPC-type carbapenemase 56:144 Differential Th17 response induced by the two clades of the pandemic ST258 Klebsiella pneumoniae clonal lineages producing KPC-type carbapenemase. 28586386 7 15 theme immunity 1920:1927 arg1 response 1899:1906 a different response 1887:1906 a different response of adaptive immunity 1887:1927 Altogether, present results suggest that CG258-KP of the two clades are capable of inducing a different response of adaptive immunity in the human host. 28586386 0 16 theme lineages 104:111 arg1 clades 46:51 the two clades 38:51 the two clades of the pandemic ST258 Klebsiella pneumoniae clonal lineages producing KPC-type carbapenemase 38:144 Differential Th17 response induced by the two clades of the pandemic ST258 Klebsiella pneumoniae clonal lineages producing KPC-type carbapenemase. 28586386 5 17 theme myeloid 1324:1330 arg1 cells 1342:1346 myeloid dendritic cells 1324:1346 myeloid dendritic cells 1324:1346 While no differences in the rate of bacterial internalization or in the bacteria-induced expression of CD86 and HLA-DR by monocytes and myeloid dendritic cells were revealed, we found that the two strains significantly differ in inducing the production of cytokines involved in the adaptive immune response, as IL-1β, IL-23 and TNF-α, by antigen-presenting cells, with KKBO-1 being a more efficient inducer than KK207-1. 28586386 4 18 with cultures 1132:1139 arg1 KKBO-1 1146:1151 KKBO-1 1146:1151 KKBO-1 1146:1151 Our data showed that KKBO-1 (clade 2) induces a Th17 response more efficiently than KK207-1 (clade 1): the percentage of CD4+IL17+ cells and the production of IL-17A were significantly higher in cultures with KKBO-1 compared to cultures with KK207-1. 28586386 6 19 theme virulent 1708:1715 arg1 strain 1741:1746 a highly virulent K. pneumoniae reference strain 1699:1746 a highly virulent K. pneumoniae reference strain known to escape immune-inflammatory responses 1699:1792 The immune responses elicited by KK207-1 were comparable to those elicited by CIP 52.145, a highly virulent K. pneumoniae reference strain known to escape immune-inflammatory responses. 28586386 6 19 theme virulent 1708:1715 arg1 52.145 1691:1696 CIP 52.145 1687:1696 CIP 52.145 1687:1696 The immune responses elicited by KK207-1 were comparable to those elicited by CIP 52.145, a highly virulent K. pneumoniae reference strain known to escape immune-inflammatory responses. 28586386 5 20 theme cytokines 1444:1452 arg1 production 1430:1439 the production 1426:1439 the production of cytokines involved in the adaptive immune response 1426:1493 While no differences in the rate of bacterial internalization or in the bacteria-induced expression of CD86 and HLA-DR by monocytes and myeloid dendritic cells were revealed, we found that the two strains significantly differ in inducing the production of cytokines involved in the adaptive immune response, as IL-1β, IL-23 and TNF-α, by antigen-presenting cells, with KKBO-1 being a more efficient inducer than KK207-1. 28586386 1 21 theme carbapenemases 170:183 arg1 spread 151:156 The spread 147:156 The spread of KPC-type carbapenemases 147:183 The spread of KPC-type carbapenemases is mainly attributed to the global dissemination of Klebsiella pneumoniae (KP) strains belonging to the clonal group (CG) 258, including sequence type (ST) 258 and other related STs. 28586386 0 22 theme clonal 97:102 arg1 lineages 104:111 the pandemic ST258 Klebsiella pneumoniae clonal lineages 56:111 the pandemic ST258 Klebsiella pneumoniae clonal lineages producing KPC-type carbapenemase 56:144 Differential Th17 response induced by the two clades of the pandemic ST258 Klebsiella pneumoniae clonal lineages producing KPC-type carbapenemase. 28586386 6 23 theme CIP 1687:1689 arg1 52.145 1691:1696 CIP 52.145 1687:1696 CIP 52.145 1687:1696 The immune responses elicited by KK207-1 were comparable to those elicited by CIP 52.145, a highly virulent K. pneumoniae reference strain known to escape immune-inflammatory responses. 28586386 6 23 theme CIP 1687:1689 arg1 strain 1741:1746 a highly virulent K. pneumoniae reference strain 1699:1746 a highly virulent K. pneumoniae reference strain known to escape immune-inflammatory responses 1699:1792 The immune responses elicited by KK207-1 were comparable to those elicited by CIP 52.145, a highly virulent K. pneumoniae reference strain known to escape immune-inflammatory responses. 28586386 5 24 theme immune 1479:1484 arg1 response 1486:1493 the adaptive immune response 1466:1493 the adaptive immune response 1466:1493 While no differences in the rate of bacterial internalization or in the bacteria-induced expression of CD86 and HLA-DR by monocytes and myeloid dendritic cells were revealed, we found that the two strains significantly differ in inducing the production of cytokines involved in the adaptive immune response, as IL-1β, IL-23 and TNF-α, by antigen-presenting cells, with KKBO-1 being a more efficient inducer than KK207-1. 28586386 2 25 theme polysaccharide 627:640 arg1 locus 648:652 the capsular polysaccharide (cps) locus 614:652 the capsular polysaccharide (cps) locus 614:652 Two distinct clades of CG258-KP have evolved, which differ mainly for the composition of their capsular polysaccharides, and recent studies indicate that clade 1 evolved from an ancestor of clade 2 by recombination of a genomic fragment carrying the capsular polysaccharide (cps) locus. 28586386 0 26 dep Klebsiella 75:84 arg1 pneumoniae 86:95 pneumoniae 86:95 pneumoniae 86:95 Differential Th17 response induced by the two clades of the pandemic ST258 Klebsiella pneumoniae clonal lineages producing KPC-type carbapenemase. 28586386 2 27 theme capsular 463:470 arg1 polysaccharides 472:486 their capsular polysaccharides 457:486 their capsular polysaccharides 457:486 Two distinct clades of CG258-KP have evolved, which differ mainly for the composition of their capsular polysaccharides, and recent studies indicate that clade 1 evolved from an ancestor of clade 2 by recombination of a genomic fragment carrying the capsular polysaccharide (cps) locus. 28586386 0 28 theme Th17 13:16 arg1 response 18:25 Differential Th17 response 0:25 Differential Th17 response 0:25 Differential Th17 response induced by the two clades of the pandemic ST258 Klebsiella pneumoniae clonal lineages producing KPC-type carbapenemase. 28586386 5 29 theme adaptive 1470:1477 arg1 response 1486:1493 the adaptive immune response 1466:1493 the adaptive immune response 1466:1493 While no differences in the rate of bacterial internalization or in the bacteria-induced expression of CD86 and HLA-DR by monocytes and myeloid dendritic cells were revealed, we found that the two strains significantly differ in inducing the production of cytokines involved in the adaptive immune response, as IL-1β, IL-23 and TNF-α, by antigen-presenting cells, with KKBO-1 being a more efficient inducer than KK207-1. 28586386 2 30 theme capsular 618:625 arg1 cps 643:645 cps 643:645 cps 643:645 Two distinct clades of CG258-KP have evolved, which differ mainly for the composition of their capsular polysaccharides, and recent studies indicate that clade 1 evolved from an ancestor of clade 2 by recombination of a genomic fragment carrying the capsular polysaccharide (cps) locus. 28586386 2 30 theme capsular 618:625 arg1 polysaccharide 627:640 the capsular polysaccharide 614:640 the capsular polysaccharide (cps) locus 614:652 Two distinct clades of CG258-KP have evolved, which differ mainly for the composition of their capsular polysaccharides, and recent studies indicate that clade 1 evolved from an ancestor of clade 2 by recombination of a genomic fragment carrying the capsular polysaccharide (cps) locus. 28586386 0 31 theme Differential 0:11 arg1 response 18:25 Differential Th17 response 0:25 Differential Th17 response 0:25 Differential Th17 response induced by the two clades of the pandemic ST258 Klebsiella pneumoniae clonal lineages producing KPC-type carbapenemase. 28586386 2 32 theme clade 558:562 arg1 ancestor 546:553 an ancestor 543:553 an ancestor of clade 2 543:564 Two distinct clades of CG258-KP have evolved, which differ mainly for the composition of their capsular polysaccharides, and recent studies indicate that clade 1 evolved from an ancestor of clade 2 by recombination of a genomic fragment carrying the capsular polysaccharide (cps) locus. 28586386 5 33 theme CD86 1291:1294 arg1 expression 1277:1286 the bacteria-induced expression 1256:1286 the bacteria-induced expression of CD86 and HLA-DR by monocytes and myeloid dendritic cells 1256:1346 While no differences in the rate of bacterial internalization or in the bacteria-induced expression of CD86 and HLA-DR by monocytes and myeloid dendritic cells were revealed, we found that the two strains significantly differ in inducing the production of cytokines involved in the adaptive immune response, as IL-1β, IL-23 and TNF-α, by antigen-presenting cells, with KKBO-1 being a more efficient inducer than KK207-1. 28586386 3 34 theme adaptive 833:840 arg1 response 849:856 an adaptive immune response 830:856 an adaptive immune response 830:856 In this paper, we investigated the ability of two ST258-KP strains, KKBO-1 and KK207-1, selected as representatives of ST258-KP clade 2 and clade 1, respectively, to activate an adaptive immune response using ex vivo-stimulation of PBMC from normal donors as an experimental model. 28586386 6 35 theme reference 1731:1739 arg1 strain 1741:1746 a highly virulent K. pneumoniae reference strain 1699:1746 a highly virulent K. pneumoniae reference strain known to escape immune-inflammatory responses 1699:1792 The immune responses elicited by KK207-1 were comparable to those elicited by CIP 52.145, a highly virulent K. pneumoniae reference strain known to escape immune-inflammatory responses. 28586386 6 35 theme reference 1731:1739 arg1 52.145 1691:1696 CIP 52.145 1687:1696 CIP 52.145 1687:1696 The immune responses elicited by KK207-1 were comparable to those elicited by CIP 52.145, a highly virulent K. pneumoniae reference strain known to escape immune-inflammatory responses. 28586386 2 36 theme CG258-KP 391:398 arg1 clades 381:386 Two distinct clades 368:386 Two distinct clades of CG258-KP 368:398 Two distinct clades of CG258-KP have evolved, which differ mainly for the composition of their capsular polysaccharides, and recent studies indicate that clade 1 evolved from an ancestor of clade 2 by recombination of a genomic fragment carrying the capsular polysaccharide (cps) locus. 28586386 1 37 dep type 331:334 arg1 ST 337:338 ST 337:338 ST 337:338 The spread of KPC-type carbapenemases is mainly attributed to the global dissemination of Klebsiella pneumoniae (KP) strains belonging to the clonal group (CG) 258, including sequence type (ST) 258 and other related STs. 28586386 0 38 theme KPC-type 123:130 arg1 carbapenemase 132:144 KPC-type carbapenemase 123:144 KPC-type carbapenemase 123:144 Differential Th17 response induced by the two clades of the pandemic ST258 Klebsiella pneumoniae clonal lineages producing KPC-type carbapenemase. 28586386 3 39 theme immune 842:847 arg1 response 849:856 an adaptive immune response 830:856 an adaptive immune response 830:856 In this paper, we investigated the ability of two ST258-KP strains, KKBO-1 and KK207-1, selected as representatives of ST258-KP clade 2 and clade 1, respectively, to activate an adaptive immune response using ex vivo-stimulation of PBMC from normal donors as an experimental model. 28586386 6 40 theme pneumoniae 1720:1729 arg1 strain 1741:1746 a highly virulent K. pneumoniae reference strain 1699:1746 a highly virulent K. pneumoniae reference strain known to escape immune-inflammatory responses 1699:1792 The immune responses elicited by KK207-1 were comparable to those elicited by CIP 52.145, a highly virulent K. pneumoniae reference strain known to escape immune-inflammatory responses. 28586386 6 40 theme pneumoniae 1720:1729 arg1 52.145 1691:1696 CIP 52.145 1687:1696 CIP 52.145 1687:1696 The immune responses elicited by KK207-1 were comparable to those elicited by CIP 52.145, a highly virulent K. pneumoniae reference strain known to escape immune-inflammatory responses. 28586386 1 41 theme clonal 289:294 arg1 CG 303:304 the clonal group (CG) 258 285:309 the clonal group (CG) 258 285:309 The spread of KPC-type carbapenemases is mainly attributed to the global dissemination of Klebsiella pneumoniae (KP) strains belonging to the clonal group (CG) 258, including sequence type (ST) 258 and other related STs. 28586386 5 42 theme efficient 1577:1585 arg1 inducer 1587:1593 a more efficient inducer 1570:1593 a more efficient inducer than KK207-1 1570:1606 While no differences in the rate of bacterial internalization or in the bacteria-induced expression of CD86 and HLA-DR by monocytes and myeloid dendritic cells were revealed, we found that the two strains significantly differ in inducing the production of cytokines involved in the adaptive immune response, as IL-1β, IL-23 and TNF-α, by antigen-presenting cells, with KKBO-1 being a more efficient inducer than KK207-1. 28586386 5 42 theme efficient 1577:1585 arg1 KKBO-1 1557:1562 KKBO-1 1557:1562 KKBO-1 1557:1562 While no differences in the rate of bacterial internalization or in the bacteria-induced expression of CD86 and HLA-DR by monocytes and myeloid dendritic cells were revealed, we found that the two strains significantly differ in inducing the production of cytokines involved in the adaptive immune response, as IL-1β, IL-23 and TNF-α, by antigen-presenting cells, with KKBO-1 being a more efficient inducer than KK207-1. 28586386 2 43 theme distinct 372:379 arg1 clades 381:386 Two distinct clades 368:386 Two distinct clades of CG258-KP 368:398 Two distinct clades of CG258-KP have evolved, which differ mainly for the composition of their capsular polysaccharides, and recent studies indicate that clade 1 evolved from an ancestor of clade 2 by recombination of a genomic fragment carrying the capsular polysaccharide (cps) locus. 28586386 2 44 contain carrying 605:612 arg1 fragment 596:603 a genomic fragment 586:603 a genomic fragment carrying the capsular polysaccharide (cps) locus 586:652 Two distinct clades of CG258-KP have evolved, which differ mainly for the composition of their capsular polysaccharides, and recent studies indicate that clade 1 evolved from an ancestor of clade 2 by recombination of a genomic fragment carrying the capsular polysaccharide (cps) locus. 28586386 2 44 contain carrying 605:612 arg2 locus 648:652 the capsular polysaccharide (cps) locus 614:652 the capsular polysaccharide (cps) locus 614:652 Two distinct clades of CG258-KP have evolved, which differ mainly for the composition of their capsular polysaccharides, and recent studies indicate that clade 1 evolved from an ancestor of clade 2 by recombination of a genomic fragment carrying the capsular polysaccharide (cps) locus. 28586386 1 45 theme group 296:300 arg1 CG 303:304 the clonal group (CG) 258 285:309 the clonal group (CG) 258 285:309 The spread of KPC-type carbapenemases is mainly attributed to the global dissemination of Klebsiella pneumoniae (KP) strains belonging to the clonal group (CG) 258, including sequence type (ST) 258 and other related STs. 28586386 2 46 theme recent 493:498 arg1 studies 500:506 recent studies 493:506 recent studies 493:506 Two distinct clades of CG258-KP have evolved, which differ mainly for the composition of their capsular polysaccharides, and recent studies indicate that clade 1 evolved from an ancestor of clade 2 by recombination of a genomic fragment carrying the capsular polysaccharide (cps) locus. 28586386 1 47 theme other 349:353 arg1 STs 363:365 other related STs 349:365 other related STs 349:365 The spread of KPC-type carbapenemases is mainly attributed to the global dissemination of Klebsiella pneumoniae (KP) strains belonging to the clonal group (CG) 258, including sequence type (ST) 258 and other related STs. 28586386 1 48 theme global 213:218 arg1 dissemination 220:232 the global dissemination 209:232 the global dissemination of Klebsiella pneumoniae (KP) strains belonging to the clonal group (CG) 258, including sequence type (ST) 258 and other related STs 209:365 The spread of KPC-type carbapenemases is mainly attributed to the global dissemination of Klebsiella pneumoniae (KP) strains belonging to the clonal group (CG) 258, including sequence type (ST) 258 and other related STs. 28586386 4 49 with cultures 1165:1172 arg1 KK207-1 1179:1185 KK207-1 1179:1185 KK207-1 1179:1185 Our data showed that KKBO-1 (clade 2) induces a Th17 response more efficiently than KK207-1 (clade 1): the percentage of CD4+IL17+ cells and the production of IL-17A were significantly higher in cultures with KKBO-1 compared to cultures with KK207-1. 28586386 1 50 theme related 355:361 arg1 STs 363:365 other related STs 349:365 other related STs 349:365 The spread of KPC-type carbapenemases is mainly attributed to the global dissemination of Klebsiella pneumoniae (KP) strains belonging to the clonal group (CG) 258, including sequence type (ST) 258 and other related STs. 28586386 3 51 theme ex 864:865 arg1 vivo-stimulation 867:882 ex vivo-stimulation 864:882 ex vivo-stimulation of PBMC from normal donors 864:909 In this paper, we investigated the ability of two ST258-KP strains, KKBO-1 and KK207-1, selected as representatives of ST258-KP clade 2 and clade 1, respectively, to activate an adaptive immune response using ex vivo-stimulation of PBMC from normal donors as an experimental model. 28586386 3 51 theme ex 864:865 arg1 model 930:934 an experimental model 914:934 an experimental model 914:934 In this paper, we investigated the ability of two ST258-KP strains, KKBO-1 and KK207-1, selected as representatives of ST258-KP clade 2 and clade 1, respectively, to activate an adaptive immune response using ex vivo-stimulation of PBMC from normal donors as an experimental model. 28586386 3 52 from vivo-stimulation 867:882 arg1 donors 904:909 normal donors 897:909 normal donors 897:909 In this paper, we investigated the ability of two ST258-KP strains, KKBO-1 and KK207-1, selected as representatives of ST258-KP clade 2 and clade 1, respectively, to activate an adaptive immune response using ex vivo-stimulation of PBMC from normal donors as an experimental model. 28586386 3 53 theme ST258-KP 705:712 arg1 KKBO-1 723:728 KKBO-1 723:728 KKBO-1 723:728 In this paper, we investigated the ability of two ST258-KP strains, KKBO-1 and KK207-1, selected as representatives of ST258-KP clade 2 and clade 1, respectively, to activate an adaptive immune response using ex vivo-stimulation of PBMC from normal donors as an experimental model. 28586386 3 53 theme ST258-KP 705:712 arg1 strains 714:720 two ST258-KP strains 701:720 two ST258-KP strains 701:720 In this paper, we investigated the ability of two ST258-KP strains, KKBO-1 and KK207-1, selected as representatives of ST258-KP clade 2 and clade 1, respectively, to activate an adaptive immune response using ex vivo-stimulation of PBMC from normal donors as an experimental model. 28586386 3 53 theme ST258-KP 705:712 arg1 KK207-1 734:740 KK207-1 734:740 KK207-1 734:740 In this paper, we investigated the ability of two ST258-KP strains, KKBO-1 and KK207-1, selected as representatives of ST258-KP clade 2 and clade 1, respectively, to activate an adaptive immune response using ex vivo-stimulation of PBMC from normal donors as an experimental model. 28586386 1 54 dep Klebsiella 237:246 arg1 pneumoniae 248:257 Klebsiella pneumoniae 237:257 Klebsiella pneumoniae (KP) strains 237:270 The spread of KPC-type carbapenemases is mainly attributed to the global dissemination of Klebsiella pneumoniae (KP) strains belonging to the clonal group (CG) 258, including sequence type (ST) 258 and other related STs. 28586386 6 55 theme immune 1613:1618 arg1 responses 1620:1628 The immune responses 1609:1628 The immune responses elicited by KK207-1 1609:1648 The immune responses elicited by KK207-1 were comparable to those elicited by CIP 52.145, a highly virulent K. pneumoniae reference strain known to escape immune-inflammatory responses. 28586386 6 55 theme immune 1613:1618 arg1 comparable 1655:1664 comparable 1655:1664 comparable 1655:1664 The immune responses elicited by KK207-1 were comparable to those elicited by CIP 52.145, a highly virulent K. pneumoniae reference strain known to escape immune-inflammatory responses. 28586386 4 56 theme IL-17A 1096:1101 arg1 percentage 1044:1053 the percentage 1040:1053 the percentage of CD4+IL17+ cells 1040:1072 Our data showed that KKBO-1 (clade 2) induces a Th17 response more efficiently than KK207-1 (clade 1): the percentage of CD4+IL17+ cells and the production of IL-17A were significantly higher in cultures with KKBO-1 compared to cultures with KK207-1. 28586386 4 56 theme IL-17A 1096:1101 arg1 higher 1122:1127 higher 1122:1127 higher 1122:1127 Our data showed that KKBO-1 (clade 2) induces a Th17 response more efficiently than KK207-1 (clade 1): the percentage of CD4+IL17+ cells and the production of IL-17A were significantly higher in cultures with KKBO-1 compared to cultures with KK207-1. 28586386 4 56 theme IL-17A 1096:1101 arg1 production 1082:1091 the production 1078:1091 the production of IL-17A 1078:1101 Our data showed that KKBO-1 (clade 2) induces a Th17 response more efficiently than KK207-1 (clade 1): the percentage of CD4+IL17+ cells and the production of IL-17A were significantly higher in cultures with KKBO-1 compared to cultures with KK207-1. 28586386 5 57 theme dendritic 1332:1340 arg1 cells 1342:1346 myeloid dendritic cells 1324:1346 myeloid dendritic cells 1324:1346 While no differences in the rate of bacterial internalization or in the bacteria-induced expression of CD86 and HLA-DR by monocytes and myeloid dendritic cells were revealed, we found that the two strains significantly differ in inducing the production of cytokines involved in the adaptive immune response, as IL-1β, IL-23 and TNF-α, by antigen-presenting cells, with KKBO-1 being a more efficient inducer than KK207-1. 28586386 4 58 theme CD4+IL17+ 1058:1066 arg1 cells 1068:1072 CD4+IL17+ cells 1058:1072 CD4+IL17+ cells 1058:1072 Our data showed that KKBO-1 (clade 2) induces a Th17 response more efficiently than KK207-1 (clade 1): the percentage of CD4+IL17+ cells and the production of IL-17A were significantly higher in cultures with KKBO-1 compared to cultures with KK207-1. 28586386 4 59 theme Th17 985:988 arg1 response 990:997 a Th17 response 983:997 a Th17 response 983:997 Our data showed that KKBO-1 (clade 2) induces a Th17 response more efficiently than KK207-1 (clade 1): the percentage of CD4+IL17+ cells and the production of IL-17A were significantly higher in cultures with KKBO-1 compared to cultures with KK207-1. 28586386 3 60 theme ST258-KP 774:781 arg1 clade 783:787 ST258-KP clade 2 774:789 ST258-KP clade 2 774:789 In this paper, we investigated the ability of two ST258-KP strains, KKBO-1 and KK207-1, selected as representatives of ST258-KP clade 2 and clade 1, respectively, to activate an adaptive immune response using ex vivo-stimulation of PBMC from normal donors as an experimental model. 28586386 3 61 theme experimental 917:928 arg1 vivo-stimulation 867:882 ex vivo-stimulation 864:882 ex vivo-stimulation of PBMC from normal donors 864:909 In this paper, we investigated the ability of two ST258-KP strains, KKBO-1 and KK207-1, selected as representatives of ST258-KP clade 2 and clade 1, respectively, to activate an adaptive immune response using ex vivo-stimulation of PBMC from normal donors as an experimental model. 28586386 3 61 theme experimental 917:928 arg1 model 930:934 an experimental model 914:934 an experimental model 914:934 In this paper, we investigated the ability of two ST258-KP strains, KKBO-1 and KK207-1, selected as representatives of ST258-KP clade 2 and clade 1, respectively, to activate an adaptive immune response using ex vivo-stimulation of PBMC from normal donors as an experimental model. 28586386 3 62 theme clade 783:787 arg1 representatives 755:769 representatives 755:769 representatives of ST258-KP clade 2 and clade 1, respectively 755:815 In this paper, we investigated the ability of two ST258-KP strains, KKBO-1 and KK207-1, selected as representatives of ST258-KP clade 2 and clade 1, respectively, to activate an adaptive immune response using ex vivo-stimulation of PBMC from normal donors as an experimental model. 28586386 5 63 theme bacteria-induced 1260:1275 arg1 expression 1277:1286 the bacteria-induced expression 1256:1286 the bacteria-induced expression of CD86 and HLA-DR by monocytes and myeloid dendritic cells 1256:1346 While no differences in the rate of bacterial internalization or in the bacteria-induced expression of CD86 and HLA-DR by monocytes and myeloid dendritic cells were revealed, we found that the two strains significantly differ in inducing the production of cytokines involved in the adaptive immune response, as IL-1β, IL-23 and TNF-α, by antigen-presenting cells, with KKBO-1 being a more efficient inducer than KK207-1. 28586386 7 64 theme human 1936:1940 arg1 host 1942:1945 the human host 1932:1945 the human host 1932:1945 Altogether, present results suggest that CG258-KP of the two clades are capable of inducing a different response of adaptive immunity in the human host. 28586386 1 65 theme Klebsiella 237:246 arg1 STs 363:365 other related STs 349:365 other related STs 349:365 The spread of KPC-type carbapenemases is mainly attributed to the global dissemination of Klebsiella pneumoniae (KP) strains belonging to the clonal group (CG) 258, including sequence type (ST) 258 and other related STs. 28586386 1 65 theme Klebsiella 237:246 arg1 type 331:334 sequence type (ST) 258 322:343 sequence type (ST) 258 322:343 The spread of KPC-type carbapenemases is mainly attributed to the global dissemination of Klebsiella pneumoniae (KP) strains belonging to the clonal group (CG) 258, including sequence type (ST) 258 and other related STs. 28586386 1 65 theme Klebsiella 237:246 arg1 strains 264:270 Klebsiella pneumoniae (KP) strains 237:270 Klebsiella pneumoniae (KP) strains 237:270 The spread of KPC-type carbapenemases is mainly attributed to the global dissemination of Klebsiella pneumoniae (KP) strains belonging to the clonal group (CG) 258, including sequence type (ST) 258 and other related STs. 28586386 1 65 theme Klebsiella 237:246 arg1 KP 260:261 KP 260:261 KP 260:261 The spread of KPC-type carbapenemases is mainly attributed to the global dissemination of Klebsiella pneumoniae (KP) strains belonging to the clonal group (CG) 258, including sequence type (ST) 258 and other related STs. 28586386 5 66 theme antigen-presenting 1526:1543 arg1 cells 1545:1549 antigen-presenting cells 1526:1549 antigen-presenting cells 1526:1549 While no differences in the rate of bacterial internalization or in the bacteria-induced expression of CD86 and HLA-DR by monocytes and myeloid dendritic cells were revealed, we found that the two strains significantly differ in inducing the production of cytokines involved in the adaptive immune response, as IL-1β, IL-23 and TNF-α, by antigen-presenting cells, with KKBO-1 being a more efficient inducer than KK207-1. 28586386 3 67 theme normal 897:902 arg1 donors 904:909 normal donors 897:909 normal donors 897:909 In this paper, we investigated the ability of two ST258-KP strains, KKBO-1 and KK207-1, selected as representatives of ST258-KP clade 2 and clade 1, respectively, to activate an adaptive immune response using ex vivo-stimulation of PBMC from normal donors as an experimental model. 28586386 3 68 from donors 904:909 arg1 PBMC 887:890 PBMC 887:890 PBMC from normal donors 887:909 In this paper, we investigated the ability of two ST258-KP strains, KKBO-1 and KK207-1, selected as representatives of ST258-KP clade 2 and clade 1, respectively, to activate an adaptive immune response using ex vivo-stimulation of PBMC from normal donors as an experimental model. 28586386 3 68 from donors 904:909 arg1 vivo-stimulation 867:882 ex vivo-stimulation 864:882 ex vivo-stimulation of PBMC from normal donors 864:909 In this paper, we investigated the ability of two ST258-KP strains, KKBO-1 and KK207-1, selected as representatives of ST258-KP clade 2 and clade 1, respectively, to activate an adaptive immune response using ex vivo-stimulation of PBMC from normal donors as an experimental model. 28586386 3 68 from donors 904:909 arg1 model 930:934 an experimental model 914:934 an experimental model 914:934 In this paper, we investigated the ability of two ST258-KP strains, KKBO-1 and KK207-1, selected as representatives of ST258-KP clade 2 and clade 1, respectively, to activate an adaptive immune response using ex vivo-stimulation of PBMC from normal donors as an experimental model. 28586386 3 69 theme strains 714:720 arg1 ability 690:696 the ability 686:696 the ability of two ST258-KP strains, KKBO-1 and KK207-1, selected as representatives of ST258-KP clade 2 and clade 1, respectively, to activate an adaptive immune response 686:856 In this paper, we investigated the ability of two ST258-KP strains, KKBO-1 and KK207-1, selected as representatives of ST258-KP clade 2 and clade 1, respectively, to activate an adaptive immune response using ex vivo-stimulation of PBMC from normal donors as an experimental model. 28586386 7 70 theme adaptive 1911:1918 arg1 immunity 1920:1927 adaptive immunity 1911:1927 adaptive immunity 1911:1927 Altogether, present results suggest that CG258-KP of the two clades are capable of inducing a different response of adaptive immunity in the human host. 28586386 5 71 from differences 1197:1207 arg1 rate 1216:1219 the rate 1212:1219 the rate of bacterial internalization 1212:1248 While no differences in the rate of bacterial internalization or in the bacteria-induced expression of CD86 and HLA-DR by monocytes and myeloid dendritic cells were revealed, we found that the two strains significantly differ in inducing the production of cytokines involved in the adaptive immune response, as IL-1β, IL-23 and TNF-α, by antigen-presenting cells, with KKBO-1 being a more efficient inducer than KK207-1. 28586386 5 71 from differences 1197:1207 arg1 expression 1277:1286 the bacteria-induced expression 1256:1286 the bacteria-induced expression of CD86 and HLA-DR by monocytes and myeloid dendritic cells 1256:1346 While no differences in the rate of bacterial internalization or in the bacteria-induced expression of CD86 and HLA-DR by monocytes and myeloid dendritic cells were revealed, we found that the two strains significantly differ in inducing the production of cytokines involved in the adaptive immune response, as IL-1β, IL-23 and TNF-α, by antigen-presenting cells, with KKBO-1 being a more efficient inducer than KK207-1. 28586386 5 72 theme bacterial 1224:1232 arg1 internalization 1234:1248 bacterial internalization 1224:1248 bacterial internalization 1224:1248 While no differences in the rate of bacterial internalization or in the bacteria-induced expression of CD86 and HLA-DR by monocytes and myeloid dendritic cells were revealed, we found that the two strains significantly differ in inducing the production of cytokines involved in the adaptive immune response, as IL-1β, IL-23 and TNF-α, by antigen-presenting cells, with KKBO-1 being a more efficient inducer than KK207-1. 28586386 7 73 theme clades 1856:1861 arg1 CG258-KP 1836:1843 CG258-KP 1836:1843 CG258-KP of the two clades 1836:1861 Altogether, present results suggest that CG258-KP of the two clades are capable of inducing a different response of adaptive immunity in the human host. 28586386 3 74 theme clade 795:799 arg1 representatives 755:769 representatives 755:769 representatives of ST258-KP clade 2 and clade 1, respectively 755:815 In this paper, we investigated the ability of two ST258-KP strains, KKBO-1 and KK207-1, selected as representatives of ST258-KP clade 2 and clade 1, respectively, to activate an adaptive immune response using ex vivo-stimulation of PBMC from normal donors as an experimental model. 28586386 2 75 theme polysaccharides 472:486 arg1 composition 442:452 the composition 438:452 the composition of their capsular polysaccharides 438:486 Two distinct clades of CG258-KP have evolved, which differ mainly for the composition of their capsular polysaccharides, and recent studies indicate that clade 1 evolved from an ancestor of clade 2 by recombination of a genomic fragment carrying the capsular polysaccharide (cps) locus. 26950937 1 0 theme extraordinary 172:184 arg1 arsenal 186:192 an extraordinary arsenal 169:192 an extraordinary arsenal of parasite-specific organelles including the inner membrane complex (IMC), rhoptries, micronemes, and dense granules 169:310 Toxoplasma gondii maintains its intracellular life cycle using an extraordinary arsenal of parasite-specific organelles including the inner membrane complex (IMC), rhoptries, micronemes, and dense granules. 26950937 3 1 from present 535:541 arg1 organelles 552:561 these organelles 546:561 these organelles 546:561 We exploited the Vicia villosa lectin (VVL) to identify new glycosylated proteins that are present in these organelles. 26950937 4 2 theme proteins 592:599 arg1 Purification 564:575 Purification 564:575 Purification of VVL-binding proteins by lectin affinity chromatography 564:633 Purification of VVL-binding proteins by lectin affinity chromatography yielded a number of novel proteins that were subjected to further study, resulting in the identification of proteins from the dense granules, micronemes, rhoptries and IMC. 26950937 0 3 theme Lectin 83:88 arg1 Chromatography 90:103 Vicia villosa Lectin Chromatography 69:103 Vicia villosa Lectin Chromatography 69:103 Identification of Novel O-Linked Glycosylated Toxoplasma Proteins by Vicia villosa Lectin Chromatography. 26950937 5 4 theme SAG1 882:885 arg1 proteins 840:847 three proteins 834:847 three proteins identified by this approach 834:875 We then chose to focus on three proteins identified by this approach, the SAG1 repeat containing protein SRS44, the rhoptry neck protein RON11 as well as a novel IMC protein we named IMC25. 26950937 5 4 theme SAG1 882:885 arg1 repeat 887:892 the SAG1 repeat 878:892 the SAG1 repeat containing protein SRS44, the rhoptry neck protein RON11 as well as a novel IMC protein we named IMC25 878:995 We then chose to focus on three proteins identified by this approach, the SAG1 repeat containing protein SRS44, the rhoptry neck protein RON11 as well as a novel IMC protein we named IMC25. 26950937 3 5 theme glycosylated 504:515 arg1 proteins 517:524 new glycosylated proteins 500:524 new glycosylated proteins that are present in these organelles 500:561 We exploited the Vicia villosa lectin (VVL) to identify new glycosylated proteins that are present in these organelles. 26950937 4 6 theme VVL-binding 580:590 arg1 proteins 592:599 VVL-binding proteins 580:599 VVL-binding proteins 580:599 Purification of VVL-binding proteins by lectin affinity chromatography yielded a number of novel proteins that were subjected to further study, resulting in the identification of proteins from the dense granules, micronemes, rhoptries and IMC. 26950937 6 7 theme homologous 1046:1055 arg1 recombination 1057:1069 homologous recombination 1046:1069 homologous recombination 1046:1069 To assess function, we disrupted their genes by homologous recombination or CRISPR/Cas9. 26950937 8 8 from site 1353:1356 arg1 domain 1313:1318 the C-terminal domain 1298:1318 the C-terminal domain from the predicted glycosylation site 1298:1356 We also show that IMC25 undergoes substantial proteolytic processing that separates the C-terminal domain from the predicted glycosylation site. 26950937 8 9 theme predicted 1329:1337 arg1 site 1353:1356 the predicted glycosylation site 1325:1356 the predicted glycosylation site 1325:1356 We also show that IMC25 undergoes substantial proteolytic processing that separates the C-terminal domain from the predicted glycosylation site. 26950937 4 10 theme lectin 604:609 arg1 chromatography 620:633 lectin affinity chromatography 604:633 lectin affinity chromatography 604:633 Purification of VVL-binding proteins by lectin affinity chromatography yielded a number of novel proteins that were subjected to further study, resulting in the identification of proteins from the dense granules, micronemes, rhoptries and IMC. 26950937 3 11 located present 535:541 arg2 proteins 517:524 new glycosylated proteins 500:524 new glycosylated proteins that are present in these organelles 500:561 We exploited the Vicia villosa lectin (VVL) to identify new glycosylated proteins that are present in these organelles. 26950937 3 11 located present 535:541 arg1 organelles 552:561 these organelles 546:561 these organelles 546:561 We exploited the Vicia villosa lectin (VVL) to identify new glycosylated proteins that are present in these organelles. 26950937 4 12 theme proteins 661:668 arg1 number 645:650 a number 643:650 a number of novel proteins that were subjected to further study 643:705 Purification of VVL-binding proteins by lectin affinity chromatography yielded a number of novel proteins that were subjected to further study, resulting in the identification of proteins from the dense granules, micronemes, rhoptries and IMC. 26950937 4 13 theme proteins 743:750 arg1 identification 725:738 the identification 721:738 the identification of proteins from the dense granules, micronemes, rhoptries and IMC 721:805 Purification of VVL-binding proteins by lectin affinity chromatography yielded a number of novel proteins that were subjected to further study, resulting in the identification of proteins from the dense granules, micronemes, rhoptries and IMC. 26950937 4 14 from granules 767:774 arg1 proteins 743:750 proteins 743:750 proteins from the dense granules, micronemes, rhoptries and IMC 743:805 Purification of VVL-binding proteins by lectin affinity chromatography yielded a number of novel proteins that were subjected to further study, resulting in the identification of proteins from the dense granules, micronemes, rhoptries and IMC. 26950937 4 14 from granules 767:774 arg1 identification 725:738 the identification 721:738 the identification of proteins from the dense granules, micronemes, rhoptries and IMC 721:805 Purification of VVL-binding proteins by lectin affinity chromatography yielded a number of novel proteins that were subjected to further study, resulting in the identification of proteins from the dense granules, micronemes, rhoptries and IMC. 26950937 3 15 gly glycosylated 504:515 arg1 proteins 517:524 new glycosylated proteins 500:524 new glycosylated proteins that are present in these organelles 500:561 We exploited the Vicia villosa lectin (VVL) to identify new glycosylated proteins that are present in these organelles. 26950937 2 16 theme protein 396:402 arg1 constituents 404:415 their protein constituents 390:415 their protein constituents 390:415 While these unique compartments play critical roles in pathogenesis, many of their protein constituents have yet to be identified. 26950937 9 17 theme efficient 1432:1440 arg1 chromatography 1411:1424 lectin affinity chromatography 1395:1424 lectin affinity chromatography 1395:1424 Together, we have demonstrated that lectin affinity chromatography is an efficient method of identifying new glycosylated parasite-specific proteins. 26950937 9 17 theme efficient 1432:1440 arg1 method 1442:1447 an efficient method 1429:1447 an efficient method of identifying new glycosylated parasite-specific proteins 1429:1506 Together, we have demonstrated that lectin affinity chromatography is an efficient method of identifying new glycosylated parasite-specific proteins. 26950937 9 18 theme affinity 1402:1409 arg1 chromatography 1411:1424 lectin affinity chromatography 1395:1424 lectin affinity chromatography 1395:1424 Together, we have demonstrated that lectin affinity chromatography is an efficient method of identifying new glycosylated parasite-specific proteins. 26950937 9 18 theme affinity 1402:1409 arg1 method 1442:1447 an efficient method 1429:1447 an efficient method of identifying new glycosylated parasite-specific proteins 1429:1506 Together, we have demonstrated that lectin affinity chromatography is an efficient method of identifying new glycosylated parasite-specific proteins. 26950937 4 19 theme affinity 611:618 arg1 chromatography 620:633 lectin affinity chromatography 604:633 lectin affinity chromatography 604:633 Purification of VVL-binding proteins by lectin affinity chromatography yielded a number of novel proteins that were subjected to further study, resulting in the identification of proteins from the dense granules, micronemes, rhoptries and IMC. 26950937 2 20 theme constituents 404:415 arg1 constituents 404:415 their protein constituents 390:415 their protein constituents 390:415 While these unique compartments play critical roles in pathogenesis, many of their protein constituents have yet to be identified. 26950937 2 20 theme constituents 404:415 arg1 many 382:385 many 382:385 many 382:385 While these unique compartments play critical roles in pathogenesis, many of their protein constituents have yet to be identified. 26950937 7 21 theme intracellular 1190:1202 arg1 survival 1204:1211 intracellular survival 1190:1211 intracellular survival 1190:1211 The knockouts were all successful, demonstrating that these proteins are not essential for invasion or intracellular survival. 26950937 5 22 theme neck 932:935 arg1 protein 905:911 protein SRS44 905:917 protein SRS44 905:917 We then chose to focus on three proteins identified by this approach, the SAG1 repeat containing protein SRS44, the rhoptry neck protein RON11 as well as a novel IMC protein we named IMC25. 26950937 5 22 theme neck 932:935 arg1 RON11 945:949 the rhoptry neck protein RON11 920:949 the rhoptry neck protein RON11 920:949 We then chose to focus on three proteins identified by this approach, the SAG1 repeat containing protein SRS44, the rhoptry neck protein RON11 as well as a novel IMC protein we named IMC25. 26950937 1 23 theme organelles 215:224 arg1 arsenal 186:192 an extraordinary arsenal 169:192 an extraordinary arsenal of parasite-specific organelles including the inner membrane complex (IMC), rhoptries, micronemes, and dense granules 169:310 Toxoplasma gondii maintains its intracellular life cycle using an extraordinary arsenal of parasite-specific organelles including the inner membrane complex (IMC), rhoptries, micronemes, and dense granules. 26950937 2 24 theme unique 325:330 arg1 compartments 332:343 these unique compartments 319:343 these unique compartments 319:343 While these unique compartments play critical roles in pathogenesis, many of their protein constituents have yet to be identified. 26950937 5 25 dep protein 974:980 arg1 we 982:983 we 982:983 we 982:983 We then chose to focus on three proteins identified by this approach, the SAG1 repeat containing protein SRS44, the rhoptry neck protein RON11 as well as a novel IMC protein we named IMC25. 26950937 0 26 theme O-Linked 24:31 arg1 Proteins 57:64 Novel O-Linked Glycosylated Toxoplasma Proteins 18:64 Novel O-Linked Glycosylated Toxoplasma Proteins 18:64 Identification of Novel O-Linked Glycosylated Toxoplasma Proteins by Vicia villosa Lectin Chromatography. 26950937 1 27 theme dense 297:301 arg1 granules 303:310 dense granules 297:310 dense granules 297:310 Toxoplasma gondii maintains its intracellular life cycle using an extraordinary arsenal of parasite-specific organelles including the inner membrane complex (IMC), rhoptries, micronemes, and dense granules. 26950937 4 28 theme dense 761:765 arg1 IMC 803:805 IMC 803:805 IMC 803:805 Purification of VVL-binding proteins by lectin affinity chromatography yielded a number of novel proteins that were subjected to further study, resulting in the identification of proteins from the dense granules, micronemes, rhoptries and IMC. 26950937 4 28 theme dense 761:765 arg1 rhoptries 789:797 rhoptries 789:797 rhoptries 789:797 Purification of VVL-binding proteins by lectin affinity chromatography yielded a number of novel proteins that were subjected to further study, resulting in the identification of proteins from the dense granules, micronemes, rhoptries and IMC. 26950937 4 28 theme dense 761:765 arg1 micronemes 777:786 micronemes 777:786 micronemes 777:786 Purification of VVL-binding proteins by lectin affinity chromatography yielded a number of novel proteins that were subjected to further study, resulting in the identification of proteins from the dense granules, micronemes, rhoptries and IMC. 26950937 4 28 theme dense 761:765 arg1 granules 767:774 the dense granules 757:774 the dense granules 757:774 Purification of VVL-binding proteins by lectin affinity chromatography yielded a number of novel proteins that were subjected to further study, resulting in the identification of proteins from the dense granules, micronemes, rhoptries and IMC. 26950937 9 29 theme new 1464:1466 arg1 proteins 1499:1506 new glycosylated parasite-specific proteins 1464:1506 new glycosylated parasite-specific proteins 1464:1506 Together, we have demonstrated that lectin affinity chromatography is an efficient method of identifying new glycosylated parasite-specific proteins. 26950937 1 30 theme Toxoplasma 106:115 arg1 gondii 117:122 Toxoplasma gondii 106:122 Toxoplasma gondii 106:122 Toxoplasma gondii maintains its intracellular life cycle using an extraordinary arsenal of parasite-specific organelles including the inner membrane complex (IMC), rhoptries, micronemes, and dense granules. 26950937 8 31 gly glycosylation 1339:1351 arg2 site 1353:1356 the predicted glycosylation site 1325:1356 the predicted glycosylation site 1325:1356 We also show that IMC25 undergoes substantial proteolytic processing that separates the C-terminal domain from the predicted glycosylation site. 26950937 5 32 theme rhoptry 924:930 arg1 protein 905:911 protein SRS44 905:917 protein SRS44 905:917 We then chose to focus on three proteins identified by this approach, the SAG1 repeat containing protein SRS44, the rhoptry neck protein RON11 as well as a novel IMC protein we named IMC25. 26950937 5 32 theme rhoptry 924:930 arg1 RON11 945:949 the rhoptry neck protein RON11 920:949 the rhoptry neck protein RON11 920:949 We then chose to focus on three proteins identified by this approach, the SAG1 repeat containing protein SRS44, the rhoptry neck protein RON11 as well as a novel IMC protein we named IMC25. 26950937 5 33 theme protein 937:943 arg1 protein 905:911 protein SRS44 905:917 protein SRS44 905:917 We then chose to focus on three proteins identified by this approach, the SAG1 repeat containing protein SRS44, the rhoptry neck protein RON11 as well as a novel IMC protein we named IMC25. 26950937 5 33 theme protein 937:943 arg1 RON11 945:949 the rhoptry neck protein RON11 920:949 the rhoptry neck protein RON11 920:949 We then chose to focus on three proteins identified by this approach, the SAG1 repeat containing protein SRS44, the rhoptry neck protein RON11 as well as a novel IMC protein we named IMC25. 26950937 3 34 attach present 535:541 arg2 proteins 517:524 new glycosylated proteins 500:524 new glycosylated proteins that are present in these organelles 500:561 We exploited the Vicia villosa lectin (VVL) to identify new glycosylated proteins that are present in these organelles. 26950937 3 34 attach present 535:541 arg1 organelles 552:561 these organelles 546:561 these organelles 546:561 We exploited the Vicia villosa lectin (VVL) to identify new glycosylated proteins that are present in these organelles. 26950937 1 35 theme inner 240:244 arg1 IMC 264:266 IMC 264:266 IMC 264:266 Toxoplasma gondii maintains its intracellular life cycle using an extraordinary arsenal of parasite-specific organelles including the inner membrane complex (IMC), rhoptries, micronemes, and dense granules. 26950937 1 35 theme inner 240:244 arg1 complex 255:261 the inner membrane complex 236:261 the inner membrane complex (IMC) 236:267 Toxoplasma gondii maintains its intracellular life cycle using an extraordinary arsenal of parasite-specific organelles including the inner membrane complex (IMC), rhoptries, micronemes, and dense granules. 26950937 0 36 theme Toxoplasma 46:55 arg1 Proteins 57:64 Novel O-Linked Glycosylated Toxoplasma Proteins 18:64 Novel O-Linked Glycosylated Toxoplasma Proteins 18:64 Identification of Novel O-Linked Glycosylated Toxoplasma Proteins by Vicia villosa Lectin Chromatography. 26950937 8 37 theme proteolytic 1260:1270 arg1 processing 1272:1281 substantial proteolytic processing 1248:1281 substantial proteolytic processing that separates the C-terminal domain from the predicted glycosylation site 1248:1356 We also show that IMC25 undergoes substantial proteolytic processing that separates the C-terminal domain from the predicted glycosylation site. 26950937 3 38 theme Vicia 461:465 arg1 VVL 483:485 VVL 483:485 VVL 483:485 We exploited the Vicia villosa lectin (VVL) to identify new glycosylated proteins that are present in these organelles. 26950937 3 38 theme Vicia 461:465 arg1 lectin 475:480 the Vicia villosa lectin 457:480 the Vicia villosa lectin (VVL) 457:486 We exploited the Vicia villosa lectin (VVL) to identify new glycosylated proteins that are present in these organelles. 26950937 1 39 theme membrane 246:253 arg1 IMC 264:266 IMC 264:266 IMC 264:266 Toxoplasma gondii maintains its intracellular life cycle using an extraordinary arsenal of parasite-specific organelles including the inner membrane complex (IMC), rhoptries, micronemes, and dense granules. 26950937 1 39 theme membrane 246:253 arg1 complex 255:261 the inner membrane complex 236:261 the inner membrane complex (IMC) 236:267 Toxoplasma gondii maintains its intracellular life cycle using an extraordinary arsenal of parasite-specific organelles including the inner membrane complex (IMC), rhoptries, micronemes, and dense granules. 26950937 0 40 theme Glycosylated 33:44 arg1 Proteins 57:64 Novel O-Linked Glycosylated Toxoplasma Proteins 18:64 Novel O-Linked Glycosylated Toxoplasma Proteins 18:64 Identification of Novel O-Linked Glycosylated Toxoplasma Proteins by Vicia villosa Lectin Chromatography. 26950937 8 41 theme substantial 1248:1258 arg1 processing 1272:1281 substantial proteolytic processing 1248:1281 substantial proteolytic processing that separates the C-terminal domain from the predicted glycosylation site 1248:1356 We also show that IMC25 undergoes substantial proteolytic processing that separates the C-terminal domain from the predicted glycosylation site. 26950937 3 42 theme villosa 467:473 arg1 VVL 483:485 VVL 483:485 VVL 483:485 We exploited the Vicia villosa lectin (VVL) to identify new glycosylated proteins that are present in these organelles. 26950937 3 42 theme villosa 467:473 arg1 lectin 475:480 the Vicia villosa lectin 457:480 the Vicia villosa lectin (VVL) 457:486 We exploited the Vicia villosa lectin (VVL) to identify new glycosylated proteins that are present in these organelles. 26950937 3 43 theme new 500:502 arg1 proteins 517:524 new glycosylated proteins 500:524 new glycosylated proteins that are present in these organelles 500:561 We exploited the Vicia villosa lectin (VVL) to identify new glycosylated proteins that are present in these organelles. 26950937 9 44 theme parasite-specific 1481:1497 arg1 proteins 1499:1506 new glycosylated parasite-specific proteins 1464:1506 new glycosylated parasite-specific proteins 1464:1506 Together, we have demonstrated that lectin affinity chromatography is an efficient method of identifying new glycosylated parasite-specific proteins. 26950937 0 45 theme Proteins 57:64 arg1 Identification 0:13 Identification 0:13 Identification of Novel O-Linked Glycosylated Toxoplasma Proteins by Vicia villosa Lectin Chromatography. 0:104 Identification of Novel O-Linked Glycosylated Toxoplasma Proteins by Vicia villosa Lectin Chromatography. 26950937 9 46 gly glycosylated 1468:1479 arg1 proteins 1499:1506 new glycosylated parasite-specific proteins 1464:1506 new glycosylated parasite-specific proteins 1464:1506 Together, we have demonstrated that lectin affinity chromatography is an efficient method of identifying new glycosylated parasite-specific proteins. 26950937 9 47 theme glycosylated 1468:1479 arg1 proteins 1499:1506 new glycosylated parasite-specific proteins 1464:1506 new glycosylated parasite-specific proteins 1464:1506 Together, we have demonstrated that lectin affinity chromatography is an efficient method of identifying new glycosylated parasite-specific proteins. 26950937 1 48 theme intracellular 138:150 arg1 cycle 157:161 its intracellular life cycle 134:161 its intracellular life cycle using an extraordinary arsenal of parasite-specific organelles including the inner membrane complex (IMC), rhoptries, micronemes, and dense granules 134:310 Toxoplasma gondii maintains its intracellular life cycle using an extraordinary arsenal of parasite-specific organelles including the inner membrane complex (IMC), rhoptries, micronemes, and dense granules. 26950937 3 49 from organelles 552:561 arg1 present 535:541 present 535:541 present 535:541 We exploited the Vicia villosa lectin (VVL) to identify new glycosylated proteins that are present in these organelles. 26950937 5 50 contain containing 894:903 arg1 proteins 840:847 three proteins 834:847 three proteins identified by this approach 834:875 We then chose to focus on three proteins identified by this approach, the SAG1 repeat containing protein SRS44, the rhoptry neck protein RON11 as well as a novel IMC protein we named IMC25. 26950937 5 50 contain containing 894:903 arg2 protein 905:911 protein SRS44 905:917 protein SRS44 905:917 We then chose to focus on three proteins identified by this approach, the SAG1 repeat containing protein SRS44, the rhoptry neck protein RON11 as well as a novel IMC protein we named IMC25. 26950937 5 50 contain containing 894:903 arg1 repeat 887:892 the SAG1 repeat 878:892 the SAG1 repeat containing protein SRS44, the rhoptry neck protein RON11 as well as a novel IMC protein we named IMC25 878:995 We then chose to focus on three proteins identified by this approach, the SAG1 repeat containing protein SRS44, the rhoptry neck protein RON11 as well as a novel IMC protein we named IMC25. 26950937 5 50 contain containing 894:903 arg2 protein 974:980 a novel IMC protein 962:980 protein SRS44, the rhoptry neck protein RON11 as well as a novel IMC protein we named IMC25 905:995 We then chose to focus on three proteins identified by this approach, the SAG1 repeat containing protein SRS44, the rhoptry neck protein RON11 as well as a novel IMC protein we named IMC25. 26950937 5 50 contain containing 894:903 arg2 RON11 945:949 the rhoptry neck protein RON11 920:949 the rhoptry neck protein RON11 920:949 We then chose to focus on three proteins identified by this approach, the SAG1 repeat containing protein SRS44, the rhoptry neck protein RON11 as well as a novel IMC protein we named IMC25. 26950937 1 51 theme life 152:155 arg1 cycle 157:161 its intracellular life cycle 134:161 its intracellular life cycle using an extraordinary arsenal of parasite-specific organelles including the inner membrane complex (IMC), rhoptries, micronemes, and dense granules 134:310 Toxoplasma gondii maintains its intracellular life cycle using an extraordinary arsenal of parasite-specific organelles including the inner membrane complex (IMC), rhoptries, micronemes, and dense granules. 26950937 4 52 from identification 725:738 arg1 IMC 803:805 IMC 803:805 IMC 803:805 Purification of VVL-binding proteins by lectin affinity chromatography yielded a number of novel proteins that were subjected to further study, resulting in the identification of proteins from the dense granules, micronemes, rhoptries and IMC. 26950937 4 52 from identification 725:738 arg1 rhoptries 789:797 rhoptries 789:797 rhoptries 789:797 Purification of VVL-binding proteins by lectin affinity chromatography yielded a number of novel proteins that were subjected to further study, resulting in the identification of proteins from the dense granules, micronemes, rhoptries and IMC. 26950937 4 52 from identification 725:738 arg1 micronemes 777:786 micronemes 777:786 micronemes 777:786 Purification of VVL-binding proteins by lectin affinity chromatography yielded a number of novel proteins that were subjected to further study, resulting in the identification of proteins from the dense granules, micronemes, rhoptries and IMC. 26950937 4 52 from identification 725:738 arg1 granules 767:774 the dense granules 757:774 the dense granules 757:774 Purification of VVL-binding proteins by lectin affinity chromatography yielded a number of novel proteins that were subjected to further study, resulting in the identification of proteins from the dense granules, micronemes, rhoptries and IMC. 26950937 8 53 theme glycosylation 1339:1351 arg1 site 1353:1356 the predicted glycosylation site 1325:1356 the predicted glycosylation site 1325:1356 We also show that IMC25 undergoes substantial proteolytic processing that separates the C-terminal domain from the predicted glycosylation site. 26950937 5 54 theme novel 964:968 arg1 protein 974:980 a novel IMC protein 962:980 protein SRS44, the rhoptry neck protein RON11 as well as a novel IMC protein we named IMC25 905:995 We then chose to focus on three proteins identified by this approach, the SAG1 repeat containing protein SRS44, the rhoptry neck protein RON11 as well as a novel IMC protein we named IMC25. 26950937 2 55 theme critical 350:357 arg1 roles 359:363 critical roles 350:363 critical roles 350:363 While these unique compartments play critical roles in pathogenesis, many of their protein constituents have yet to be identified. 26950937 0 56 theme villosa 75:81 arg1 Chromatography 90:103 Vicia villosa Lectin Chromatography 69:103 Vicia villosa Lectin Chromatography 69:103 Identification of Novel O-Linked Glycosylated Toxoplasma Proteins by Vicia villosa Lectin Chromatography. 26950937 4 57 theme novel 655:659 arg1 proteins 661:668 novel proteins 655:668 novel proteins that were subjected to further study 655:705 Purification of VVL-binding proteins by lectin affinity chromatography yielded a number of novel proteins that were subjected to further study, resulting in the identification of proteins from the dense granules, micronemes, rhoptries and IMC. 26950937 5 58 theme IMC 970:972 arg1 protein 974:980 a novel IMC protein 962:980 protein SRS44, the rhoptry neck protein RON11 as well as a novel IMC protein we named IMC25 905:995 We then chose to focus on three proteins identified by this approach, the SAG1 repeat containing protein SRS44, the rhoptry neck protein RON11 as well as a novel IMC protein we named IMC25. 26950937 8 59 theme C-terminal 1302:1311 arg1 domain 1313:1318 the C-terminal domain 1298:1318 the C-terminal domain from the predicted glycosylation site 1298:1356 We also show that IMC25 undergoes substantial proteolytic processing that separates the C-terminal domain from the predicted glycosylation site. 26950937 1 60 theme parasite-specific 197:213 arg1 organelles 215:224 parasite-specific organelles 197:224 parasite-specific organelles including the inner membrane complex (IMC), rhoptries, micronemes, and dense granules 197:310 Toxoplasma gondii maintains its intracellular life cycle using an extraordinary arsenal of parasite-specific organelles including the inner membrane complex (IMC), rhoptries, micronemes, and dense granules. 26950937 1 60 theme parasite-specific 197:213 arg1 granules 303:310 dense granules 297:310 dense granules 297:310 Toxoplasma gondii maintains its intracellular life cycle using an extraordinary arsenal of parasite-specific organelles including the inner membrane complex (IMC), rhoptries, micronemes, and dense granules. 26950937 1 60 theme parasite-specific 197:213 arg1 micronemes 281:290 micronemes 281:290 micronemes 281:290 Toxoplasma gondii maintains its intracellular life cycle using an extraordinary arsenal of parasite-specific organelles including the inner membrane complex (IMC), rhoptries, micronemes, and dense granules. 26950937 1 60 theme parasite-specific 197:213 arg1 rhoptries 270:278 rhoptries 270:278 rhoptries 270:278 Toxoplasma gondii maintains its intracellular life cycle using an extraordinary arsenal of parasite-specific organelles including the inner membrane complex (IMC), rhoptries, micronemes, and dense granules. 26950937 1 60 theme parasite-specific 197:213 arg1 complex 255:261 the inner membrane complex 236:261 the inner membrane complex (IMC) 236:267 Toxoplasma gondii maintains its intracellular life cycle using an extraordinary arsenal of parasite-specific organelles including the inner membrane complex (IMC), rhoptries, micronemes, and dense granules. 26950937 0 61 theme Vicia 69:73 arg1 Chromatography 90:103 Vicia villosa Lectin Chromatography 69:103 Vicia villosa Lectin Chromatography 69:103 Identification of Novel O-Linked Glycosylated Toxoplasma Proteins by Vicia villosa Lectin Chromatography. 26950937 0 62 theme Novel 18:22 arg1 Proteins 57:64 Novel O-Linked Glycosylated Toxoplasma Proteins 18:64 Novel O-Linked Glycosylated Toxoplasma Proteins 18:64 Identification of Novel O-Linked Glycosylated Toxoplasma Proteins by Vicia villosa Lectin Chromatography. 26950937 4 63 theme further 693:699 arg1 study 701:705 further study 693:705 further study 693:705 Purification of VVL-binding proteins by lectin affinity chromatography yielded a number of novel proteins that were subjected to further study, resulting in the identification of proteins from the dense granules, micronemes, rhoptries and IMC. 26950937 9 64 theme lectin 1395:1400 arg1 chromatography 1411:1424 lectin affinity chromatography 1395:1424 lectin affinity chromatography 1395:1424 Together, we have demonstrated that lectin affinity chromatography is an efficient method of identifying new glycosylated parasite-specific proteins. 26950937 9 64 theme lectin 1395:1400 arg1 method 1442:1447 an efficient method 1429:1447 an efficient method of identifying new glycosylated parasite-specific proteins 1429:1506 Together, we have demonstrated that lectin affinity chromatography is an efficient method of identifying new glycosylated parasite-specific proteins. 26412745 5 0 theme continuous 720:729 arg1 decline 731:737 continuous decline 720:737 continuous decline after middle cerebral artery occlusion (MCAO) in the mouse brain 720:802 We also found a dynamic elevation of protein O-GlcNAcylation during the first four hours of cerebral ischemia, followed by continuous decline after middle cerebral artery occlusion (MCAO) in the mouse brain. 26412745 7 1 theme ischemic 975:982 arg1 tissue 990:995 ischemic brain tissue 975:995 ischemic brain tissue 975:995 Finally, we found a negative correlation between AKT phosphorylation and O-GlcNAcylation in ischemic brain tissue. 26412745 8 2 theme activity 1143:1150 arg1 down-regulation 1120:1134 down-regulation 1120:1134 down-regulation of AKT activity 1120:1150 These results indicate that cerebral ischemia induces a rapid increase of O-GlcNAcylation that promotes apoptosis through down-regulation of AKT activity. 26412745 2 3 link O-linked 268:275 arg1 β-N-acetylglucosamine 277:297 O-linked β-N-acetylglucosamine 268:297 O-linked β-N-acetylglucosamine (GlcNAc) 268:306 In this study, we found that O-GlcNAcylation, a unique protein posttranslational modification with O-linked β-N-acetylglucosamine (GlcNAc), promoted apoptosis through attenuating phosphorylation/activation of AKT and Bad. 26412745 2 3 link O-linked 268:275 arg1 GlcNAc 300:305 GlcNAc 300:305 GlcNAc 300:305 In this study, we found that O-GlcNAcylation, a unique protein posttranslational modification with O-linked β-N-acetylglucosamine (GlcNAc), promoted apoptosis through attenuating phosphorylation/activation of AKT and Bad. 26412745 3 4 theme co-immunoprecipitation 400:421 arg1 techniques 439:448 co-immunoprecipitation and mutagenesis techniques 400:448 co-immunoprecipitation and mutagenesis techniques 400:448 By using co-immunoprecipitation and mutagenesis techniques, we identified O-GlcNAc modification at both Thr308 and Ser473 of AKT. 26412745 4 5 theme AKT 592:594 arg1 over-expression 573:587 over-expression 573:587 over-expression of AKT 573:594 O-GlcNAcylation-induced apoptosis was attenuated by over-expression of AKT. 26412745 5 6 theme middle 745:750 arg1 occlusion 768:776 middle cerebral artery occlusion 745:776 middle cerebral artery occlusion (MCAO) 745:783 We also found a dynamic elevation of protein O-GlcNAcylation during the first four hours of cerebral ischemia, followed by continuous decline after middle cerebral artery occlusion (MCAO) in the mouse brain. 26412745 5 6 theme middle 745:750 arg1 MCAO 779:782 MCAO 779:782 MCAO 779:782 We also found a dynamic elevation of protein O-GlcNAcylation during the first four hours of cerebral ischemia, followed by continuous decline after middle cerebral artery occlusion (MCAO) in the mouse brain. 26412745 7 7 from O-GlcNAcylation 956:970 arg1 tissue 990:995 ischemic brain tissue 975:995 ischemic brain tissue 975:995 Finally, we found a negative correlation between AKT phosphorylation and O-GlcNAcylation in ischemic brain tissue. 26412745 9 8 theme novel 1178:1182 arg1 mechanism 1184:1192 a novel mechanism 1176:1192 a novel mechanism through which O-GlcNAcylation regulates ischemia-induced neuronal apoptosis through AKT signaling 1176:1290 These findings provide a novel mechanism through which O-GlcNAcylation regulates ischemia-induced neuronal apoptosis through AKT signaling. 26412745 5 9 theme ischemia 698:705 arg1 hours 680:684 the first four hours 665:684 the first four hours of cerebral ischemia 665:705 We also found a dynamic elevation of protein O-GlcNAcylation during the first four hours of cerebral ischemia, followed by continuous decline after middle cerebral artery occlusion (MCAO) in the mouse brain. 26412745 5 10 theme cerebral 689:696 arg1 ischemia 698:705 cerebral ischemia 689:705 cerebral ischemia 689:705 We also found a dynamic elevation of protein O-GlcNAcylation during the first four hours of cerebral ischemia, followed by continuous decline after middle cerebral artery occlusion (MCAO) in the mouse brain. 26412745 7 11 theme brain 984:988 arg1 tissue 990:995 ischemic brain tissue 975:995 ischemic brain tissue 975:995 Finally, we found a negative correlation between AKT phosphorylation and O-GlcNAcylation in ischemic brain tissue. 26412745 0 12 theme AKT 70:72 arg1 signaling 74:82 AKT signaling 70:82 AKT signaling 70:82 O-GlcNAcylation regulates ischemia-induced neuronal apoptosis through AKT signaling. 26412745 5 13 theme O-GlcNAcylation 642:656 arg1 elevation 621:629 a dynamic elevation 611:629 a dynamic elevation of protein O-GlcNAcylation 611:656 We also found a dynamic elevation of protein O-GlcNAcylation during the first four hours of cerebral ischemia, followed by continuous decline after middle cerebral artery occlusion (MCAO) in the mouse brain. 26412745 9 14 theme AKT 1278:1280 arg1 signaling 1282:1290 AKT signaling 1278:1290 AKT signaling 1278:1290 These findings provide a novel mechanism through which O-GlcNAcylation regulates ischemia-induced neuronal apoptosis through AKT signaling. 26412745 1 15 theme important 104:112 arg1 role 114:117 an important role 101:117 an important role 101:117 Apoptosis plays an important role in neural development and neurological disorders. 26412745 3 16 theme mutagenesis 427:437 arg1 techniques 439:448 co-immunoprecipitation and mutagenesis techniques 400:448 co-immunoprecipitation and mutagenesis techniques 400:448 By using co-immunoprecipitation and mutagenesis techniques, we identified O-GlcNAc modification at both Thr308 and Ser473 of AKT. 26412745 5 17 theme first 669:673 arg1 hours 680:684 the first four hours 665:684 the first four hours of cerebral ischemia 665:705 We also found a dynamic elevation of protein O-GlcNAcylation during the first four hours of cerebral ischemia, followed by continuous decline after middle cerebral artery occlusion (MCAO) in the mouse brain. 26412745 7 18 theme negative 903:910 arg1 correlation 912:922 a negative correlation 901:922 a negative correlation between AKT phosphorylation and O-GlcNAcylation in ischemic brain tissue 901:995 Finally, we found a negative correlation between AKT phosphorylation and O-GlcNAcylation in ischemic brain tissue. 26412745 0 19 theme ischemia-induced 26:41 arg1 apoptosis 52:60 ischemia-induced neuronal apoptosis 26:60 ischemia-induced neuronal apoptosis 26:60 O-GlcNAcylation regulates ischemia-induced neuronal apoptosis through AKT signaling. 26412745 8 20 theme cerebral 1026:1033 arg1 ischemia 1035:1042 cerebral ischemia 1026:1042 cerebral ischemia 1026:1042 These results indicate that cerebral ischemia induces a rapid increase of O-GlcNAcylation that promotes apoptosis through down-regulation of AKT activity. 26412745 1 21 theme neural 122:127 arg1 development 129:139 neural development 122:139 neural development 122:139 Apoptosis plays an important role in neural development and neurological disorders. 26412745 9 22 theme ischemia-induced 1234:1249 arg1 apoptosis 1260:1268 ischemia-induced neuronal apoptosis 1234:1268 ischemia-induced neuronal apoptosis 1234:1268 These findings provide a novel mechanism through which O-GlcNAcylation regulates ischemia-induced neuronal apoptosis through AKT signaling. 26412745 2 23 with modification 250:261 arg1 β-N-acetylglucosamine 277:297 O-linked β-N-acetylglucosamine 268:297 O-linked β-N-acetylglucosamine (GlcNAc) 268:306 In this study, we found that O-GlcNAcylation, a unique protein posttranslational modification with O-linked β-N-acetylglucosamine (GlcNAc), promoted apoptosis through attenuating phosphorylation/activation of AKT and Bad. 26412745 2 23 with modification 250:261 arg1 GlcNAc 300:305 GlcNAc 300:305 GlcNAc 300:305 In this study, we found that O-GlcNAcylation, a unique protein posttranslational modification with O-linked β-N-acetylglucosamine (GlcNAc), promoted apoptosis through attenuating phosphorylation/activation of AKT and Bad. 26412745 9 24 theme neuronal 1251:1258 arg1 apoptosis 1260:1268 ischemia-induced neuronal apoptosis 1234:1268 ischemia-induced neuronal apoptosis 1234:1268 These findings provide a novel mechanism through which O-GlcNAcylation regulates ischemia-induced neuronal apoptosis through AKT signaling. 26412745 4 25 theme O-GlcNAcylation-induced 521:543 arg1 apoptosis 545:553 O-GlcNAcylation-induced apoptosis 521:553 O-GlcNAcylation-induced apoptosis 521:553 O-GlcNAcylation-induced apoptosis was attenuated by over-expression of AKT. 26412745 0 26 theme neuronal 43:50 arg1 apoptosis 52:60 ischemia-induced neuronal apoptosis 26:60 ischemia-induced neuronal apoptosis 26:60 O-GlcNAcylation regulates ischemia-induced neuronal apoptosis through AKT signaling. 26412745 5 27 theme dynamic 613:619 arg1 elevation 621:629 a dynamic elevation 611:629 a dynamic elevation of protein O-GlcNAcylation 611:656 We also found a dynamic elevation of protein O-GlcNAcylation during the first four hours of cerebral ischemia, followed by continuous decline after middle cerebral artery occlusion (MCAO) in the mouse brain. 26412745 3 28 theme AKT 516:518 arg1 Ser473 506:511 Ser473 506:511 Ser473 of AKT 506:518 By using co-immunoprecipitation and mutagenesis techniques, we identified O-GlcNAc modification at both Thr308 and Ser473 of AKT. 26412745 5 29 theme mouse 792:796 arg1 brain 798:802 the mouse brain 788:802 the mouse brain 788:802 We also found a dynamic elevation of protein O-GlcNAcylation during the first four hours of cerebral ischemia, followed by continuous decline after middle cerebral artery occlusion (MCAO) in the mouse brain. 26412745 5 30 theme cerebral 752:759 arg1 occlusion 768:776 middle cerebral artery occlusion 745:776 middle cerebral artery occlusion (MCAO) 745:783 We also found a dynamic elevation of protein O-GlcNAcylation during the first four hours of cerebral ischemia, followed by continuous decline after middle cerebral artery occlusion (MCAO) in the mouse brain. 26412745 5 30 theme cerebral 752:759 arg1 MCAO 779:782 MCAO 779:782 MCAO 779:782 We also found a dynamic elevation of protein O-GlcNAcylation during the first four hours of cerebral ischemia, followed by continuous decline after middle cerebral artery occlusion (MCAO) in the mouse brain. 26412745 2 31 theme posttranslational 232:248 arg1 modification 250:261 a unique protein posttranslational modification 215:261 a unique protein posttranslational modification with O-linked β-N-acetylglucosamine (GlcNAc) 215:306 In this study, we found that O-GlcNAcylation, a unique protein posttranslational modification with O-linked β-N-acetylglucosamine (GlcNAc), promoted apoptosis through attenuating phosphorylation/activation of AKT and Bad. 26412745 2 31 theme posttranslational 232:248 arg1 O-GlcNAcylation 198:212 O-GlcNAcylation 198:212 O-GlcNAcylation 198:212 In this study, we found that O-GlcNAcylation, a unique protein posttranslational modification with O-linked β-N-acetylglucosamine (GlcNAc), promoted apoptosis through attenuating phosphorylation/activation of AKT and Bad. 26412745 6 32 theme O-GlcNAcylation 822:836 arg1 elevation 809:817 The elevation 805:817 The elevation of O-GlcNAcylation 805:836 The elevation of O-GlcNAcylation coincided with activation of cell apoptosis. 26412745 3 33 theme O-GlcNAc 465:472 arg1 modification 474:485 O-GlcNAc modification 465:485 O-GlcNAc modification 465:485 By using co-immunoprecipitation and mutagenesis techniques, we identified O-GlcNAc modification at both Thr308 and Ser473 of AKT. 26412745 5 34 theme artery 761:766 arg1 occlusion 768:776 middle cerebral artery occlusion 745:776 middle cerebral artery occlusion (MCAO) 745:783 We also found a dynamic elevation of protein O-GlcNAcylation during the first four hours of cerebral ischemia, followed by continuous decline after middle cerebral artery occlusion (MCAO) in the mouse brain. 26412745 5 34 theme artery 761:766 arg1 MCAO 779:782 MCAO 779:782 MCAO 779:782 We also found a dynamic elevation of protein O-GlcNAcylation during the first four hours of cerebral ischemia, followed by continuous decline after middle cerebral artery occlusion (MCAO) in the mouse brain. 26412745 2 35 theme unique 217:222 arg1 modification 250:261 a unique protein posttranslational modification 215:261 a unique protein posttranslational modification with O-linked β-N-acetylglucosamine (GlcNAc) 215:306 In this study, we found that O-GlcNAcylation, a unique protein posttranslational modification with O-linked β-N-acetylglucosamine (GlcNAc), promoted apoptosis through attenuating phosphorylation/activation of AKT and Bad. 26412745 2 35 theme unique 217:222 arg1 O-GlcNAcylation 198:212 O-GlcNAcylation 198:212 O-GlcNAcylation 198:212 In this study, we found that O-GlcNAcylation, a unique protein posttranslational modification with O-linked β-N-acetylglucosamine (GlcNAc), promoted apoptosis through attenuating phosphorylation/activation of AKT and Bad. 26412745 2 36 theme protein 224:230 arg1 modification 250:261 a unique protein posttranslational modification 215:261 a unique protein posttranslational modification with O-linked β-N-acetylglucosamine (GlcNAc) 215:306 In this study, we found that O-GlcNAcylation, a unique protein posttranslational modification with O-linked β-N-acetylglucosamine (GlcNAc), promoted apoptosis through attenuating phosphorylation/activation of AKT and Bad. 26412745 2 36 theme protein 224:230 arg1 O-GlcNAcylation 198:212 O-GlcNAcylation 198:212 O-GlcNAcylation 198:212 In this study, we found that O-GlcNAcylation, a unique protein posttranslational modification with O-linked β-N-acetylglucosamine (GlcNAc), promoted apoptosis through attenuating phosphorylation/activation of AKT and Bad. 26412745 7 37 dep AKT 932:934 arg1 phosphorylation 936:950 phosphorylation 936:950 phosphorylation 936:950 Finally, we found a negative correlation between AKT phosphorylation and O-GlcNAcylation in ischemic brain tissue. 26412745 2 38 theme Bad 386:388 arg1 phosphorylation/activation 348:373 phosphorylation/activation 348:373 phosphorylation/activation of AKT and Bad 348:388 In this study, we found that O-GlcNAcylation, a unique protein posttranslational modification with O-linked β-N-acetylglucosamine (GlcNAc), promoted apoptosis through attenuating phosphorylation/activation of AKT and Bad. 26412745 5 39 from decline 731:737 arg1 brain 798:802 the mouse brain 788:802 the mouse brain 788:802 We also found a dynamic elevation of protein O-GlcNAcylation during the first four hours of cerebral ischemia, followed by continuous decline after middle cerebral artery occlusion (MCAO) in the mouse brain. 26412745 6 40 theme cell 867:870 arg1 apoptosis 872:880 cell apoptosis 867:880 cell apoptosis 867:880 The elevation of O-GlcNAcylation coincided with activation of cell apoptosis. 26412745 5 41 theme protein 634:640 arg1 O-GlcNAcylation 642:656 protein O-GlcNAcylation 634:656 protein O-GlcNAcylation 634:656 We also found a dynamic elevation of protein O-GlcNAcylation during the first four hours of cerebral ischemia, followed by continuous decline after middle cerebral artery occlusion (MCAO) in the mouse brain. 26412745 1 42 theme neurological 145:156 arg1 disorders 158:166 neurological disorders 145:166 neurological disorders 145:166 Apoptosis plays an important role in neural development and neurological disorders. 26412745 2 43 theme AKT 378:380 arg1 phosphorylation/activation 348:373 phosphorylation/activation 348:373 phosphorylation/activation of AKT and Bad 348:388 In this study, we found that O-GlcNAcylation, a unique protein posttranslational modification with O-linked β-N-acetylglucosamine (GlcNAc), promoted apoptosis through attenuating phosphorylation/activation of AKT and Bad. 26412745 6 44 theme apoptosis 872:880 arg1 activation 853:862 activation 853:862 activation of cell apoptosis 853:880 The elevation of O-GlcNAcylation coincided with activation of cell apoptosis. 26412745 8 45 theme AKT 1139:1141 arg1 activity 1143:1150 AKT activity 1139:1150 AKT activity 1139:1150 These results indicate that cerebral ischemia induces a rapid increase of O-GlcNAcylation that promotes apoptosis through down-regulation of AKT activity. 26412745 7 46 from AKT 932:934 arg1 tissue 990:995 ischemic brain tissue 975:995 ischemic brain tissue 975:995 Finally, we found a negative correlation between AKT phosphorylation and O-GlcNAcylation in ischemic brain tissue. 26412745 8 47 theme O-GlcNAcylation 1072:1086 arg1 increase 1060:1067 a rapid increase 1052:1067 a rapid increase of O-GlcNAcylation that promotes apoptosis through down-regulation of AKT activity 1052:1150 These results indicate that cerebral ischemia induces a rapid increase of O-GlcNAcylation that promotes apoptosis through down-regulation of AKT activity. 26412745 2 48 theme O-linked 268:275 arg1 β-N-acetylglucosamine 277:297 O-linked β-N-acetylglucosamine 268:297 O-linked β-N-acetylglucosamine (GlcNAc) 268:306 In this study, we found that O-GlcNAcylation, a unique protein posttranslational modification with O-linked β-N-acetylglucosamine (GlcNAc), promoted apoptosis through attenuating phosphorylation/activation of AKT and Bad. 26412745 2 48 theme O-linked 268:275 arg1 GlcNAc 300:305 GlcNAc 300:305 GlcNAc 300:305 In this study, we found that O-GlcNAcylation, a unique protein posttranslational modification with O-linked β-N-acetylglucosamine (GlcNAc), promoted apoptosis through attenuating phosphorylation/activation of AKT and Bad. 26412745 8 49 theme rapid 1054:1058 arg1 increase 1060:1067 a rapid increase 1052:1067 a rapid increase of O-GlcNAcylation that promotes apoptosis through down-regulation of AKT activity 1052:1150 These results indicate that cerebral ischemia induces a rapid increase of O-GlcNAcylation that promotes apoptosis through down-regulation of AKT activity. 25703305 4 0 theme based 602:606 arg1 approach 619:626 a [3+3] nitrilium based convergent approach 584:626 a [3+3] nitrilium based convergent approach 584:626 Hexasaccharide 10 was chemically synthesized for the first time by a [3+3] nitrilium based convergent approach, using the trichloroacetimidate method of glycosylation. 25703305 2 1 theme β-D-Galp- 208:216 arg1 carbohydrates 369:381 the largest carbohydrates 357:381 the largest carbohydrates in mucins of some strains of Trypanosoma cruzi 357:428 The hexasaccharide β-D-Galp-(1→2)-[β-D-Galp-(1→3)]-β-D-Galp-(1→6)-[β-D-Galp(1→2)-β-D-Galf(1→4)]-D-GlcNAc (10) and its β-D-Galf-(1→2)-β-D-Galf containing isomer (7) are the largest carbohydrates in mucins of some strains of Trypanosoma cruzi. 25703305 2 1 theme β-D-Galp- 208:216 arg1 -[β-D-Galp- 222:232 The hexasaccharide β-D-Galp-(1→2)-[β-D-Galp-(1→3)]-β-D-Galp-(1→6)-[β-D-Galp(1→2)-β-D-Galf(1→4)]-D-GlcNAc (10) and its β-D-Galf-(1→2)-β-D-Galf containing isomer (7) 189:351 The hexasaccharide β-D-Galp-(1→2)-[β-D-Galp-(1→3)]-β-D-Galp-(1→6)-[β-D-Galp(1→2)-β-D-Galf(1→4)]-D-GlcNAc (10) and its β-D-Galf-(1→2)-β-D-Galf containing isomer (7) 189:351 The hexasaccharide β-D-Galp-(1→2)-[β-D-Galp-(1→3)]-β-D-Galp-(1→6)-[β-D-Galp(1→2)-β-D-Galf(1→4)]-D-GlcNAc (10) and its β-D-Galf-(1→2)-β-D-Galf containing isomer (7) are the largest carbohydrates in mucins of some strains of Trypanosoma cruzi. 25703305 0 2 link O-linked 17:24 arg1 hexasaccharide 26:39 the O-linked hexasaccharide 13:39 the O-linked hexasaccharide 13:39 Synthesis of the O-linked hexasaccharide containing β-D-Galp-(1→2)-D-Galf in Trypanosoma cruzi mucins. 25703305 5 3 theme H 692:692 arg1 identical 726:734 identical 726:734 identical 726:734 The (1)H NMR spectrum of its alditol was identical to the spectrum of the product released by β-elimination from the parasite mucin. 25703305 5 3 theme H 692:692 arg1 spectrum 698:705 The (1)H NMR spectrum 685:705 The (1)H NMR spectrum of its alditol 685:720 The (1)H NMR spectrum of its alditol was identical to the spectrum of the product released by β-elimination from the parasite mucin. 25703305 3 4 theme β-D-Galp 444:451 arg1 sites 463:467 sites 463:467 sites of sialylation 463:482 The terminal β-D-Galp units are sites of sialylation by the parasite trans-sialidase. 25703305 3 4 theme β-D-Galp 444:451 arg1 units 453:457 The terminal β-D-Galp units 431:457 The terminal β-D-Galp units 431:457 The terminal β-D-Galp units are sites of sialylation by the parasite trans-sialidase. 25703305 3 4 theme β-D-Galp 444:451 arg1 sialylation 472:482 sialylation 472:482 sialylation 472:482 The terminal β-D-Galp units are sites of sialylation by the parasite trans-sialidase. 25703305 6 5 theme 10 884:885 arg1 glycoside 871:879 the benzyl glycoside 860:879 the benzyl glycoside of 10 860:885 The trans-sialylation reaction studied on the benzyl glycoside of 10 showed two monosialylated products whose relative abundance changed with time. 25703305 2 6 theme cruzi 424:428 arg1 strains 401:407 some strains 396:407 some strains of Trypanosoma cruzi 396:428 The hexasaccharide β-D-Galp-(1→2)-[β-D-Galp-(1→3)]-β-D-Galp-(1→6)-[β-D-Galp(1→2)-β-D-Galf(1→4)]-D-GlcNAc (10) and its β-D-Galf-(1→2)-β-D-Galf containing isomer (7) are the largest carbohydrates in mucins of some strains of Trypanosoma cruzi. 25703305 4 7 theme glycosylation 670:682 arg1 method 660:665 the trichloroacetimidate method 635:665 the trichloroacetimidate method of glycosylation 635:682 Hexasaccharide 10 was chemically synthesized for the first time by a [3+3] nitrilium based convergent approach, using the trichloroacetimidate method of glycosylation. 25703305 2 8 theme -[β-D-Galp 254:263 arg1 -D-GlcNAc 284:292 -β-D-Galp-(1→6)-[β-D-Galp(1→2)-β-D-Galf(1→4)]-D-GlcNAc (10) 239:297 -β-D-Galp-(1→6)-[β-D-Galp(1→2)-β-D-Galf(1→4)]-D-GlcNAc (10) 239:297 The hexasaccharide β-D-Galp-(1→2)-[β-D-Galp-(1→3)]-β-D-Galp-(1→6)-[β-D-Galp(1→2)-β-D-Galf(1→4)]-D-GlcNAc (10) and its β-D-Galf-(1→2)-β-D-Galf containing isomer (7) are the largest carbohydrates in mucins of some strains of Trypanosoma cruzi. 25703305 5 9 attach released 767:774 arg2 product 759:765 the product 755:765 the product released by β-elimination from the parasite mucin 755:815 The (1)H NMR spectrum of its alditol was identical to the spectrum of the product released by β-elimination from the parasite mucin. 25703305 5 9 attach released 767:774 arg1 mucin 811:815 the parasite mucin 798:815 the parasite mucin 798:815 The (1)H NMR spectrum of its alditol was identical to the spectrum of the product released by β-elimination from the parasite mucin. 25703305 8 10 theme product 1132:1138 arg1 synthesis 1074:1082 A preparative synthesis 1060:1082 A preparative synthesis of the latter 1060:1096 A preparative synthesis of the latter and spectroscopic analysis of the product unequivocally established the sialylation site at the less hindered (1→3)-linked galactopyranose. 25703305 8 10 theme product 1132:1138 arg1 analysis 1116:1123 spectroscopic analysis 1102:1123 spectroscopic analysis of the product 1102:1138 A preparative synthesis of the latter and spectroscopic analysis of the product unequivocally established the sialylation site at the less hindered (1→3)-linked galactopyranose. 25703305 1 11 theme constituent 160:170 arg1 hexasaccharides 172:186 the two constituent hexasaccharides 152:186 the two constituent hexasaccharides 152:186 Differences on sialylation by trans-sialidase of the two constituent hexasaccharides. 25703305 5 12 theme NMR 694:696 arg1 identical 726:734 identical 726:734 identical 726:734 The (1)H NMR spectrum of its alditol was identical to the spectrum of the product released by β-elimination from the parasite mucin. 25703305 5 12 theme NMR 694:696 arg1 spectrum 698:705 The (1)H NMR spectrum 685:705 The (1)H NMR spectrum of its alditol 685:720 The (1)H NMR spectrum of its alditol was identical to the spectrum of the product released by β-elimination from the parasite mucin. 25703305 2 13 theme 1→6 250:252 arg1 -D-GlcNAc 284:292 -β-D-Galp-(1→6)-[β-D-Galp(1→2)-β-D-Galf(1→4)]-D-GlcNAc (10) 239:297 -β-D-Galp-(1→6)-[β-D-Galp(1→2)-β-D-Galf(1→4)]-D-GlcNAc (10) 239:297 The hexasaccharide β-D-Galp-(1→2)-[β-D-Galp-(1→3)]-β-D-Galp-(1→6)-[β-D-Galp(1→2)-β-D-Galf(1→4)]-D-GlcNAc (10) and its β-D-Galf-(1→2)-β-D-Galf containing isomer (7) are the largest carbohydrates in mucins of some strains of Trypanosoma cruzi. 25703305 1 14 theme hexasaccharides 172:186 arg1 trans-sialidase 133:147 trans-sialidase 133:147 trans-sialidase of the two constituent hexasaccharides 133:186 Differences on sialylation by trans-sialidase of the two constituent hexasaccharides. 25703305 7 15 theme 7 1057:1057 arg1 glycoside 1044:1052 the benzyl glycoside 1033:1052 the benzyl glycoside of 7 1033:1057 On the other hand, only one product was produced by sialylation of the benzyl glycoside of 7. 25703305 2 16 from carbohydrates 369:381 arg1 mucins 386:391 mucins 386:391 mucins of some strains of Trypanosoma cruzi 386:428 The hexasaccharide β-D-Galp-(1→2)-[β-D-Galp-(1→3)]-β-D-Galp-(1→6)-[β-D-Galp(1→2)-β-D-Galf(1→4)]-D-GlcNAc (10) and its β-D-Galf-(1→2)-β-D-Galf containing isomer (7) are the largest carbohydrates in mucins of some strains of Trypanosoma cruzi. 25703305 4 17 theme trichloroacetimidate 639:658 arg1 method 660:665 the trichloroacetimidate method 635:665 the trichloroacetimidate method of glycosylation 635:682 Hexasaccharide 10 was chemically synthesized for the first time by a [3+3] nitrilium based convergent approach, using the trichloroacetimidate method of glycosylation. 25703305 2 18 theme β-D-Galf- 307:315 arg1 -β-D-Galf 321:329 its β-D-Galf-(1→2)-β-D-Galf 303:329 its β-D-Galf-(1→2)-β-D-Galf 303:329 The hexasaccharide β-D-Galp-(1→2)-[β-D-Galp-(1→3)]-β-D-Galp-(1→6)-[β-D-Galp(1→2)-β-D-Galf(1→4)]-D-GlcNAc (10) and its β-D-Galf-(1→2)-β-D-Galf containing isomer (7) are the largest carbohydrates in mucins of some strains of Trypanosoma cruzi. 25703305 8 19 gly sialylation 1170:1180 arg2 site 1182:1185 the sialylation site 1166:1185 the sialylation site 1166:1185 A preparative synthesis of the latter and spectroscopic analysis of the product unequivocally established the sialylation site at the less hindered (1→3)-linked galactopyranose. 25703305 1 20 from Differences 103:113 arg1 sialylation 118:128 sialylation 118:128 sialylation by trans-sialidase of the two constituent hexasaccharides 118:186 Differences on sialylation by trans-sialidase of the two constituent hexasaccharides. 25703305 2 21 theme -β-D-Galf 269:277 arg1 -D-GlcNAc 284:292 -β-D-Galp-(1→6)-[β-D-Galp(1→2)-β-D-Galf(1→4)]-D-GlcNAc (10) 239:297 -β-D-Galp-(1→6)-[β-D-Galp(1→2)-β-D-Galf(1→4)]-D-GlcNAc (10) 239:297 The hexasaccharide β-D-Galp-(1→2)-[β-D-Galp-(1→3)]-β-D-Galp-(1→6)-[β-D-Galp(1→2)-β-D-Galf(1→4)]-D-GlcNAc (10) and its β-D-Galf-(1→2)-β-D-Galf containing isomer (7) are the largest carbohydrates in mucins of some strains of Trypanosoma cruzi. 25703305 5 22 theme product 759:765 arg1 spectrum 743:750 the spectrum 739:750 the spectrum of the product released by β-elimination from the parasite mucin 739:815 The (1)H NMR spectrum of its alditol was identical to the spectrum of the product released by β-elimination from the parasite mucin. 25703305 0 23 theme O-linked 17:24 arg1 hexasaccharide 26:39 the O-linked hexasaccharide 13:39 the O-linked hexasaccharide 13:39 Synthesis of the O-linked hexasaccharide containing β-D-Galp-(1→2)-D-Galf in Trypanosoma cruzi mucins. 25703305 6 24 theme benzyl 864:869 arg1 glycoside 871:879 the benzyl glycoside 860:879 the benzyl glycoside of 10 860:885 The trans-sialylation reaction studied on the benzyl glycoside of 10 showed two monosialylated products whose relative abundance changed with time. 25703305 8 25 dep hindered 1199:1206 arg1 -linked 1213:1219 -linked 1213:1219 -linked 1213:1219 A preparative synthesis of the latter and spectroscopic analysis of the product unequivocally established the sialylation site at the less hindered (1→3)-linked galactopyranose. 25703305 2 26 dep -D-GlcNAc 284:292 arg1 1→4 279:281 1→4 279:281 1→4 279:281 The hexasaccharide β-D-Galp-(1→2)-[β-D-Galp-(1→3)]-β-D-Galp-(1→6)-[β-D-Galp(1→2)-β-D-Galf(1→4)]-D-GlcNAc (10) and its β-D-Galf-(1→2)-β-D-Galf containing isomer (7) are the largest carbohydrates in mucins of some strains of Trypanosoma cruzi. 25703305 2 26 dep -D-GlcNAc 284:292 arg1 1→2 265:267 1→2 265:267 1→2 265:267 The hexasaccharide β-D-Galp-(1→2)-[β-D-Galp-(1→3)]-β-D-Galp-(1→6)-[β-D-Galp(1→2)-β-D-Galf(1→4)]-D-GlcNAc (10) and its β-D-Galf-(1→2)-β-D-Galf containing isomer (7) are the largest carbohydrates in mucins of some strains of Trypanosoma cruzi. 25703305 3 27 theme parasite 491:498 arg1 trans-sialidase 500:514 the parasite trans-sialidase 487:514 the parasite trans-sialidase 487:514 The terminal β-D-Galp units are sites of sialylation by the parasite trans-sialidase. 25703305 2 28 dep -[β-D-Galp- 222:232 arg1 -β-D-Galf 321:329 its β-D-Galf-(1→2)-β-D-Galf 303:329 its β-D-Galf-(1→2)-β-D-Galf 303:329 The hexasaccharide β-D-Galp-(1→2)-[β-D-Galp-(1→3)]-β-D-Galp-(1→6)-[β-D-Galp(1→2)-β-D-Galf(1→4)]-D-GlcNAc (10) and its β-D-Galf-(1→2)-β-D-Galf containing isomer (7) are the largest carbohydrates in mucins of some strains of Trypanosoma cruzi. 25703305 2 28 dep -[β-D-Galp- 222:232 arg1 1→3 234:236 1→3 234:236 1→3 234:236 The hexasaccharide β-D-Galp-(1→2)-[β-D-Galp-(1→3)]-β-D-Galp-(1→6)-[β-D-Galp(1→2)-β-D-Galf(1→4)]-D-GlcNAc (10) and its β-D-Galf-(1→2)-β-D-Galf containing isomer (7) are the largest carbohydrates in mucins of some strains of Trypanosoma cruzi. 25703305 2 28 dep -[β-D-Galp- 222:232 arg1 -D-GlcNAc 284:292 -β-D-Galp-(1→6)-[β-D-Galp(1→2)-β-D-Galf(1→4)]-D-GlcNAc (10) 239:297 -β-D-Galp-(1→6)-[β-D-Galp(1→2)-β-D-Galf(1→4)]-D-GlcNAc (10) 239:297 The hexasaccharide β-D-Galp-(1→2)-[β-D-Galp-(1→3)]-β-D-Galp-(1→6)-[β-D-Galp(1→2)-β-D-Galf(1→4)]-D-GlcNAc (10) and its β-D-Galf-(1→2)-β-D-Galf containing isomer (7) are the largest carbohydrates in mucins of some strains of Trypanosoma cruzi. 25703305 3 29 theme sialylation 472:482 arg1 sites 463:467 sites 463:467 sites of sialylation 463:482 The terminal β-D-Galp units are sites of sialylation by the parasite trans-sialidase. 25703305 3 29 theme sialylation 472:482 arg1 units 453:457 The terminal β-D-Galp units 431:457 The terminal β-D-Galp units 431:457 The terminal β-D-Galp units are sites of sialylation by the parasite trans-sialidase. 25703305 3 29 theme sialylation 472:482 arg1 sialylation 472:482 sialylation 472:482 sialylation 472:482 The terminal β-D-Galp units are sites of sialylation by the parasite trans-sialidase. 25703305 7 30 theme other 973:977 arg1 hand 979:982 the other hand 969:982 the other hand 969:982 On the other hand, only one product was produced by sialylation of the benzyl glycoside of 7. 25703305 8 31 theme latter 1091:1096 arg1 synthesis 1074:1082 A preparative synthesis 1060:1082 A preparative synthesis of the latter 1060:1096 A preparative synthesis of the latter and spectroscopic analysis of the product unequivocally established the sialylation site at the less hindered (1→3)-linked galactopyranose. 25703305 8 31 theme latter 1091:1096 arg1 analysis 1116:1123 spectroscopic analysis 1102:1123 spectroscopic analysis of the product 1102:1138 A preparative synthesis of the latter and spectroscopic analysis of the product unequivocally established the sialylation site at the less hindered (1→3)-linked galactopyranose. 25703305 5 32 theme parasite 802:809 arg1 mucin 811:815 the parasite mucin 798:815 the parasite mucin 798:815 The (1)H NMR spectrum of its alditol was identical to the spectrum of the product released by β-elimination from the parasite mucin. 25703305 0 33 from -D-Galf 66:72 arg1 mucins 95:100 mucins 95:100 mucins 95:100 Synthesis of the O-linked hexasaccharide containing β-D-Galp-(1→2)-D-Galf in Trypanosoma cruzi mucins. 25703305 0 33 from -D-Galf 66:72 arg1 Trypanosoma 77:87 Trypanosoma 77:87 Trypanosoma 77:87 Synthesis of the O-linked hexasaccharide containing β-D-Galp-(1→2)-D-Galf in Trypanosoma cruzi mucins. 25703305 2 34 dep -β-D-Galf 321:329 arg1 1→2 317:319 1→2 317:319 1→2 317:319 The hexasaccharide β-D-Galp-(1→2)-[β-D-Galp-(1→3)]-β-D-Galp-(1→6)-[β-D-Galp(1→2)-β-D-Galf(1→4)]-D-GlcNAc (10) and its β-D-Galf-(1→2)-β-D-Galf containing isomer (7) are the largest carbohydrates in mucins of some strains of Trypanosoma cruzi. 25703305 8 35 theme sialylation 1170:1180 arg1 site 1182:1185 the sialylation site 1166:1185 the sialylation site 1166:1185 A preparative synthesis of the latter and spectroscopic analysis of the product unequivocally established the sialylation site at the less hindered (1→3)-linked galactopyranose. 25703305 0 36 theme hexasaccharide 26:39 arg1 Synthesis 0:8 Synthesis 0:8 Synthesis of the O-linked hexasaccharide 0:39 Synthesis of the O-linked hexasaccharide containing β-D-Galp-(1→2)-D-Galf in Trypanosoma cruzi mucins. 25703305 7 37 theme benzyl 1037:1042 arg1 glycoside 1044:1052 the benzyl glycoside 1033:1052 the benzyl glycoside of 7 1033:1057 On the other hand, only one product was produced by sialylation of the benzyl glycoside of 7. 25703305 7 38 theme glycoside 1044:1052 arg1 sialylation 1018:1028 sialylation 1018:1028 sialylation of the benzyl glycoside of 7 1018:1057 On the other hand, only one product was produced by sialylation of the benzyl glycoside of 7. 25703305 8 39 theme preparative 1062:1072 arg1 synthesis 1074:1082 A preparative synthesis 1060:1082 A preparative synthesis of the latter 1060:1096 A preparative synthesis of the latter and spectroscopic analysis of the product unequivocally established the sialylation site at the less hindered (1→3)-linked galactopyranose. 25703305 2 40 theme largest 361:367 arg1 carbohydrates 369:381 the largest carbohydrates 357:381 the largest carbohydrates in mucins of some strains of Trypanosoma cruzi 357:428 The hexasaccharide β-D-Galp-(1→2)-[β-D-Galp-(1→3)]-β-D-Galp-(1→6)-[β-D-Galp(1→2)-β-D-Galf(1→4)]-D-GlcNAc (10) and its β-D-Galf-(1→2)-β-D-Galf containing isomer (7) are the largest carbohydrates in mucins of some strains of Trypanosoma cruzi. 25703305 2 40 theme largest 361:367 arg1 -[β-D-Galp- 222:232 The hexasaccharide β-D-Galp-(1→2)-[β-D-Galp-(1→3)]-β-D-Galp-(1→6)-[β-D-Galp(1→2)-β-D-Galf(1→4)]-D-GlcNAc (10) and its β-D-Galf-(1→2)-β-D-Galf containing isomer (7) 189:351 The hexasaccharide β-D-Galp-(1→2)-[β-D-Galp-(1→3)]-β-D-Galp-(1→6)-[β-D-Galp(1→2)-β-D-Galf(1→4)]-D-GlcNAc (10) and its β-D-Galf-(1→2)-β-D-Galf containing isomer (7) 189:351 The hexasaccharide β-D-Galp-(1→2)-[β-D-Galp-(1→3)]-β-D-Galp-(1→6)-[β-D-Galp(1→2)-β-D-Galf(1→4)]-D-GlcNAc (10) and its β-D-Galf-(1→2)-β-D-Galf containing isomer (7) are the largest carbohydrates in mucins of some strains of Trypanosoma cruzi. 25703305 0 41 theme β-D-Galp- 52:60 arg1 -D-Galf 66:72 β-D-Galp-(1→2)-D-Galf 52:72 β-D-Galp-(1→2)-D-Galf in Trypanosoma cruzi mucins 52:100 Synthesis of the O-linked hexasaccharide containing β-D-Galp-(1→2)-D-Galf in Trypanosoma cruzi mucins. 25703305 6 42 theme trans-sialylation 822:838 arg1 reaction 840:847 The trans-sialylation reaction 818:847 The trans-sialylation reaction studied on the benzyl glycoside of 10 818:885 The trans-sialylation reaction studied on the benzyl glycoside of 10 showed two monosialylated products whose relative abundance changed with time. 25703305 2 43 theme 1→2 218:220 arg1 carbohydrates 369:381 the largest carbohydrates 357:381 the largest carbohydrates in mucins of some strains of Trypanosoma cruzi 357:428 The hexasaccharide β-D-Galp-(1→2)-[β-D-Galp-(1→3)]-β-D-Galp-(1→6)-[β-D-Galp(1→2)-β-D-Galf(1→4)]-D-GlcNAc (10) and its β-D-Galf-(1→2)-β-D-Galf containing isomer (7) are the largest carbohydrates in mucins of some strains of Trypanosoma cruzi. 25703305 2 43 theme 1→2 218:220 arg1 -[β-D-Galp- 222:232 The hexasaccharide β-D-Galp-(1→2)-[β-D-Galp-(1→3)]-β-D-Galp-(1→6)-[β-D-Galp(1→2)-β-D-Galf(1→4)]-D-GlcNAc (10) and its β-D-Galf-(1→2)-β-D-Galf containing isomer (7) 189:351 The hexasaccharide β-D-Galp-(1→2)-[β-D-Galp-(1→3)]-β-D-Galp-(1→6)-[β-D-Galp(1→2)-β-D-Galf(1→4)]-D-GlcNAc (10) and its β-D-Galf-(1→2)-β-D-Galf containing isomer (7) 189:351 The hexasaccharide β-D-Galp-(1→2)-[β-D-Galp-(1→3)]-β-D-Galp-(1→6)-[β-D-Galp(1→2)-β-D-Galf(1→4)]-D-GlcNAc (10) and its β-D-Galf-(1→2)-β-D-Galf containing isomer (7) are the largest carbohydrates in mucins of some strains of Trypanosoma cruzi. 25703305 7 44 gly sialylation 1018:1028 arg1 glycoside 1044:1052 the benzyl glycoside 1033:1052 the benzyl glycoside of 7 1033:1057 On the other hand, only one product was produced by sialylation of the benzyl glycoside of 7. 25703305 4 45 theme convergent 608:617 arg1 approach 619:626 a [3+3] nitrilium based convergent approach 584:626 a [3+3] nitrilium based convergent approach 584:626 Hexasaccharide 10 was chemically synthesized for the first time by a [3+3] nitrilium based convergent approach, using the trichloroacetimidate method of glycosylation. 25703305 6 46 theme relative 928:935 arg1 abundance 937:945 abundance 937:945 abundance 937:945 The trans-sialylation reaction studied on the benzyl glycoside of 10 showed two monosialylated products whose relative abundance changed with time. 25703305 3 47 theme terminal 435:442 arg1 sites 463:467 sites 463:467 sites of sialylation 463:482 The terminal β-D-Galp units are sites of sialylation by the parasite trans-sialidase. 25703305 3 47 theme terminal 435:442 arg1 units 453:457 The terminal β-D-Galp units 431:457 The terminal β-D-Galp units 431:457 The terminal β-D-Galp units are sites of sialylation by the parasite trans-sialidase. 25703305 3 47 theme terminal 435:442 arg1 sialylation 472:482 sialylation 472:482 sialylation 472:482 The terminal β-D-Galp units are sites of sialylation by the parasite trans-sialidase. 25703305 2 48 contain containing 331:340 arg2 isomer 342:347 isomer (7) 342:351 isomer (7) 342:351 The hexasaccharide β-D-Galp-(1→2)-[β-D-Galp-(1→3)]-β-D-Galp-(1→6)-[β-D-Galp(1→2)-β-D-Galf(1→4)]-D-GlcNAc (10) and its β-D-Galf-(1→2)-β-D-Galf containing isomer (7) are the largest carbohydrates in mucins of some strains of Trypanosoma cruzi. 25703305 2 48 contain containing 331:340 arg1 carbohydrates 369:381 the largest carbohydrates 357:381 the largest carbohydrates in mucins of some strains of Trypanosoma cruzi 357:428 The hexasaccharide β-D-Galp-(1→2)-[β-D-Galp-(1→3)]-β-D-Galp-(1→6)-[β-D-Galp(1→2)-β-D-Galf(1→4)]-D-GlcNAc (10) and its β-D-Galf-(1→2)-β-D-Galf containing isomer (7) are the largest carbohydrates in mucins of some strains of Trypanosoma cruzi. 25703305 2 48 contain containing 331:340 arg1 -[β-D-Galp- 222:232 The hexasaccharide β-D-Galp-(1→2)-[β-D-Galp-(1→3)]-β-D-Galp-(1→6)-[β-D-Galp(1→2)-β-D-Galf(1→4)]-D-GlcNAc (10) and its β-D-Galf-(1→2)-β-D-Galf containing isomer (7) 189:351 The hexasaccharide β-D-Galp-(1→2)-[β-D-Galp-(1→3)]-β-D-Galp-(1→6)-[β-D-Galp(1→2)-β-D-Galf(1→4)]-D-GlcNAc (10) and its β-D-Galf-(1→2)-β-D-Galf containing isomer (7) 189:351 The hexasaccharide β-D-Galp-(1→2)-[β-D-Galp-(1→3)]-β-D-Galp-(1→6)-[β-D-Galp(1→2)-β-D-Galf(1→4)]-D-GlcNAc (10) and its β-D-Galf-(1→2)-β-D-Galf containing isomer (7) are the largest carbohydrates in mucins of some strains of Trypanosoma cruzi. 25703305 2 49 theme -β-D-Galp- 239:248 arg1 -D-GlcNAc 284:292 -β-D-Galp-(1→6)-[β-D-Galp(1→2)-β-D-Galf(1→4)]-D-GlcNAc (10) 239:297 -β-D-Galp-(1→6)-[β-D-Galp(1→2)-β-D-Galf(1→4)]-D-GlcNAc (10) 239:297 The hexasaccharide β-D-Galp-(1→2)-[β-D-Galp-(1→3)]-β-D-Galp-(1→6)-[β-D-Galp(1→2)-β-D-Galf(1→4)]-D-GlcNAc (10) and its β-D-Galf-(1→2)-β-D-Galf containing isomer (7) are the largest carbohydrates in mucins of some strains of Trypanosoma cruzi. 25703305 8 50 theme spectroscopic 1102:1114 arg1 analysis 1116:1123 spectroscopic analysis 1102:1123 spectroscopic analysis of the product 1102:1138 A preparative synthesis of the latter and spectroscopic analysis of the product unequivocally established the sialylation site at the less hindered (1→3)-linked galactopyranose. 25703305 2 51 theme strains 401:407 arg1 mucins 386:391 mucins 386:391 mucins of some strains of Trypanosoma cruzi 386:428 The hexasaccharide β-D-Galp-(1→2)-[β-D-Galp-(1→3)]-β-D-Galp-(1→6)-[β-D-Galp(1→2)-β-D-Galf(1→4)]-D-GlcNAc (10) and its β-D-Galf-(1→2)-β-D-Galf containing isomer (7) are the largest carbohydrates in mucins of some strains of Trypanosoma cruzi. 25703305 2 52 theme hexasaccharide 193:206 arg1 carbohydrates 369:381 the largest carbohydrates 357:381 the largest carbohydrates in mucins of some strains of Trypanosoma cruzi 357:428 The hexasaccharide β-D-Galp-(1→2)-[β-D-Galp-(1→3)]-β-D-Galp-(1→6)-[β-D-Galp(1→2)-β-D-Galf(1→4)]-D-GlcNAc (10) and its β-D-Galf-(1→2)-β-D-Galf containing isomer (7) are the largest carbohydrates in mucins of some strains of Trypanosoma cruzi. 25703305 2 52 theme hexasaccharide 193:206 arg1 -[β-D-Galp- 222:232 The hexasaccharide β-D-Galp-(1→2)-[β-D-Galp-(1→3)]-β-D-Galp-(1→6)-[β-D-Galp(1→2)-β-D-Galf(1→4)]-D-GlcNAc (10) and its β-D-Galf-(1→2)-β-D-Galf containing isomer (7) 189:351 The hexasaccharide β-D-Galp-(1→2)-[β-D-Galp-(1→3)]-β-D-Galp-(1→6)-[β-D-Galp(1→2)-β-D-Galf(1→4)]-D-GlcNAc (10) and its β-D-Galf-(1→2)-β-D-Galf containing isomer (7) 189:351 The hexasaccharide β-D-Galp-(1→2)-[β-D-Galp-(1→3)]-β-D-Galp-(1→6)-[β-D-Galp(1→2)-β-D-Galf(1→4)]-D-GlcNAc (10) and its β-D-Galf-(1→2)-β-D-Galf containing isomer (7) are the largest carbohydrates in mucins of some strains of Trypanosoma cruzi. 25703305 4 53 theme first 570:574 arg1 time 576:579 the first time 566:579 the first time 566:579 Hexasaccharide 10 was chemically synthesized for the first time by a [3+3] nitrilium based convergent approach, using the trichloroacetimidate method of glycosylation. 25703305 0 54 theme 1→2 62:64 arg1 -D-Galf 66:72 β-D-Galp-(1→2)-D-Galf 52:72 β-D-Galp-(1→2)-D-Galf in Trypanosoma cruzi mucins 52:100 Synthesis of the O-linked hexasaccharide containing β-D-Galp-(1→2)-D-Galf in Trypanosoma cruzi mucins. 25703305 5 55 theme alditol 714:720 arg1 identical 726:734 identical 726:734 identical 726:734 The (1)H NMR spectrum of its alditol was identical to the spectrum of the product released by β-elimination from the parasite mucin. 25703305 5 55 theme alditol 714:720 arg1 spectrum 698:705 The (1)H NMR spectrum 685:705 The (1)H NMR spectrum of its alditol 685:720 The (1)H NMR spectrum of its alditol was identical to the spectrum of the product released by β-elimination from the parasite mucin. 25703305 6 56 gly monosialylated 898:911 arg1 products 913:920 two monosialylated products 894:920 two monosialylated products whose relative abundance changed with time 894:963 The trans-sialylation reaction studied on the benzyl glycoside of 10 showed two monosialylated products whose relative abundance changed with time. 25703305 8 57 theme hindered 1199:1206 arg1 galactopyranose 1221:1235 the less hindered (1→3)-linked galactopyranose 1190:1235 the less hindered (1→3)-linked galactopyranose 1190:1235 A preparative synthesis of the latter and spectroscopic analysis of the product unequivocally established the sialylation site at the less hindered (1→3)-linked galactopyranose. 25703305 4 58 dep based 602:606 arg1 nitrilium 592:600 nitrilium 592:600 nitrilium 592:600 Hexasaccharide 10 was chemically synthesized for the first time by a [3+3] nitrilium based convergent approach, using the trichloroacetimidate method of glycosylation. 25703305 4 58 dep based 602:606 arg1 [3+3 586:589 [3+3 586:589 [3+3 586:589 Hexasaccharide 10 was chemically synthesized for the first time by a [3+3] nitrilium based convergent approach, using the trichloroacetimidate method of glycosylation. 25703305 6 59 theme monosialylated 898:911 arg1 products 913:920 two monosialylated products 894:920 two monosialylated products whose relative abundance changed with time 894:963 The trans-sialylation reaction studied on the benzyl glycoside of 10 showed two monosialylated products whose relative abundance changed with time. 25474640 4 0 with concert 689:695 arg1 PMK-1 712:716 PMK-1 712:716 PMK-1 712:716 Genetic interaction studies revealed that nutrient-responsive OGT-1 acts through the conserved β-catenin (BAR-1) pathway and in concert with p38 MAPK (PMK-1) to modulate the immune response to S. aureus. 25474640 4 0 with concert 689:695 arg1 MAPK 706:709 p38 MAPK 702:709 p38 MAPK (PMK-1) 702:717 Genetic interaction studies revealed that nutrient-responsive OGT-1 acts through the conserved β-catenin (BAR-1) pathway and in concert with p38 MAPK (PMK-1) to modulate the immune response to S. aureus. 25474640 3 1 theme human 510:514 arg1 pathogen 516:523 the human pathogen 506:523 the human pathogen S. aureus 506:533 Genetic analysis showed that deletion of O-GlcNAc transferase (ogt-1) yielded animals hypersensitive to the human pathogen S. aureus but not to P. aeruginosa. 25474640 2 2 link O-linked 257:264 arg1 O-GlcNAc 287:294 O-GlcNAc 287:294 O-GlcNAc 287:294 Using mutants defective in the enzymes of O-linked N-acetylglucosamine (O-GlcNAc) cycling, we examined the role of this nutrient-sensing pathway in the C. elegans innate immune response. 25474640 2 2 link O-linked 257:264 arg1 N-acetylglucosamine 266:284 O-linked N-acetylglucosamine 257:284 O-linked N-acetylglucosamine (O-GlcNAc) cycling 257:303 Using mutants defective in the enzymes of O-linked N-acetylglucosamine (O-GlcNAc) cycling, we examined the role of this nutrient-sensing pathway in the C. elegans innate immune response. 25474640 5 3 theme genes 916:920 arg1 deregulation 863:874 deregulation 863:874 deregulation of unique stress- and immune-responsive genes 863:920 Moreover, whole genome transcriptional profiling revealed that O-GlcNAc cycling mutants exhibited deregulation of unique stress- and immune-responsive genes. 25474640 4 4 theme p38 702:704 arg1 PMK-1 712:716 PMK-1 712:716 PMK-1 712:716 Genetic interaction studies revealed that nutrient-responsive OGT-1 acts through the conserved β-catenin (BAR-1) pathway and in concert with p38 MAPK (PMK-1) to modulate the immune response to S. aureus. 25474640 4 4 theme p38 702:704 arg1 MAPK 706:709 p38 MAPK 702:709 p38 MAPK (PMK-1) 702:717 Genetic interaction studies revealed that nutrient-responsive OGT-1 acts through the conserved β-catenin (BAR-1) pathway and in concert with p38 MAPK (PMK-1) to modulate the immune response to S. aureus. 25474640 2 5 from role 322:325 arg1 response 392:399 the C. elegans innate immune response 363:399 the C. elegans innate immune response 363:399 Using mutants defective in the enzymes of O-linked N-acetylglucosamine (O-GlcNAc) cycling, we examined the role of this nutrient-sensing pathway in the C. elegans innate immune response. 25474640 5 6 theme immune-responsive 898:914 arg1 genes 916:920 unique stress- and immune-responsive genes 879:920 unique stress- and immune-responsive genes 879:920 Moreover, whole genome transcriptional profiling revealed that O-GlcNAc cycling mutants exhibited deregulation of unique stress- and immune-responsive genes. 25474640 4 7 theme immune 735:740 arg1 response 742:749 the immune response 731:749 the immune response to S. aureus 731:762 Genetic interaction studies revealed that nutrient-responsive OGT-1 acts through the conserved β-catenin (BAR-1) pathway and in concert with p38 MAPK (PMK-1) to modulate the immune response to S. aureus. 25474640 4 8 theme nutrient-responsive 603:621 arg1 OGT-1 623:627 nutrient-responsive OGT-1 603:627 nutrient-responsive OGT-1 603:627 Genetic interaction studies revealed that nutrient-responsive OGT-1 acts through the conserved β-catenin (BAR-1) pathway and in concert with p38 MAPK (PMK-1) to modulate the immune response to S. aureus. 25474640 2 9 theme cycling 297:303 arg1 enzymes 246:252 the enzymes 242:252 the enzymes of O-linked N-acetylglucosamine (O-GlcNAc) cycling 242:303 Using mutants defective in the enzymes of O-linked N-acetylglucosamine (O-GlcNAc) cycling, we examined the role of this nutrient-sensing pathway in the C. elegans innate immune response. 25474640 3 10 theme hypersensitive 488:501 arg1 animals 480:486 animals 480:486 animals hypersensitive to the human pathogen S. aureus but not to P. aeruginosa 480:558 Genetic analysis showed that deletion of O-GlcNAc transferase (ogt-1) yielded animals hypersensitive to the human pathogen S. aureus but not to P. aeruginosa. 25474640 5 11 theme cycling 837:843 arg1 mutants 845:851 O-GlcNAc cycling mutants 828:851 O-GlcNAc cycling mutants 828:851 Moreover, whole genome transcriptional profiling revealed that O-GlcNAc cycling mutants exhibited deregulation of unique stress- and immune-responsive genes. 25474640 1 12 theme Caenorhabidits 182:195 arg1 immunity 205:212 Caenorhabidits elegans immunity 182:212 Caenorhabidits elegans immunity 182:212 Discriminating pathogenic bacteria from bacteria used as a food source is key to Caenorhabidits elegans immunity. 25474640 3 13 theme O-GlcNAc 443:450 arg1 ogt-1 465:469 ogt-1 465:469 ogt-1 465:469 Genetic analysis showed that deletion of O-GlcNAc transferase (ogt-1) yielded animals hypersensitive to the human pathogen S. aureus but not to P. aeruginosa. 25474640 3 13 theme O-GlcNAc 443:450 arg1 transferase 452:462 O-GlcNAc transferase 443:462 O-GlcNAc transferase (ogt-1) 443:470 Genetic analysis showed that deletion of O-GlcNAc transferase (ogt-1) yielded animals hypersensitive to the human pathogen S. aureus but not to P. aeruginosa. 25474640 5 14 theme transcriptional 788:802 arg1 profiling 804:812 whole genome transcriptional profiling 775:812 whole genome transcriptional profiling 775:812 Moreover, whole genome transcriptional profiling revealed that O-GlcNAc cycling mutants exhibited deregulation of unique stress- and immune-responsive genes. 25474640 2 15 dep C. 367:368 arg1 elegans 370:376 elegans 370:376 elegans 370:376 Using mutants defective in the enzymes of O-linked N-acetylglucosamine (O-GlcNAc) cycling, we examined the role of this nutrient-sensing pathway in the C. elegans innate immune response. 25474640 2 16 from enzymes 246:252 arg1 defective 229:237 defective 229:237 defective 229:237 Using mutants defective in the enzymes of O-linked N-acetylglucosamine (O-GlcNAc) cycling, we examined the role of this nutrient-sensing pathway in the C. elegans innate immune response. 25474640 3 17 theme transferase 452:462 arg1 deletion 431:438 deletion 431:438 deletion of O-GlcNAc transferase (ogt-1) 431:470 Genetic analysis showed that deletion of O-GlcNAc transferase (ogt-1) yielded animals hypersensitive to the human pathogen S. aureus but not to P. aeruginosa. 25474640 0 18 theme nutrient 10:17 arg1 transferase 35:45 Conserved nutrient sensor O-GlcNAc transferase 0:45 Conserved nutrient sensor O-GlcNAc transferase 0:45 Conserved nutrient sensor O-GlcNAc transferase is integral to C. elegans pathogen-specific immunity. 25474640 4 19 theme Genetic 561:567 arg1 studies 581:587 Genetic interaction studies 561:587 Genetic interaction studies 561:587 Genetic interaction studies revealed that nutrient-responsive OGT-1 acts through the conserved β-catenin (BAR-1) pathway and in concert with p38 MAPK (PMK-1) to modulate the immune response to S. aureus. 25474640 2 20 theme immune 385:390 arg1 response 392:399 the C. elegans innate immune response 363:399 the C. elegans innate immune response 363:399 Using mutants defective in the enzymes of O-linked N-acetylglucosamine (O-GlcNAc) cycling, we examined the role of this nutrient-sensing pathway in the C. elegans innate immune response. 25474640 0 21 theme Conserved 0:8 arg1 transferase 35:45 Conserved nutrient sensor O-GlcNAc transferase 0:45 Conserved nutrient sensor O-GlcNAc transferase 0:45 Conserved nutrient sensor O-GlcNAc transferase is integral to C. elegans pathogen-specific immunity. 25474640 2 22 theme innate 378:383 arg1 response 392:399 the C. elegans innate immune response 363:399 the C. elegans innate immune response 363:399 Using mutants defective in the enzymes of O-linked N-acetylglucosamine (O-GlcNAc) cycling, we examined the role of this nutrient-sensing pathway in the C. elegans innate immune response. 25474640 0 23 theme O-GlcNAc 26:33 arg1 transferase 35:45 Conserved nutrient sensor O-GlcNAc transferase 0:45 Conserved nutrient sensor O-GlcNAc transferase 0:45 Conserved nutrient sensor O-GlcNAc transferase is integral to C. elegans pathogen-specific immunity. 25474640 1 24 theme pathogenic 116:125 arg1 bacteria 127:134 pathogenic bacteria 116:134 pathogenic bacteria 116:134 Discriminating pathogenic bacteria from bacteria used as a food source is key to Caenorhabidits elegans immunity. 25474640 4 25 theme β-catenin 656:664 arg1 pathway 674:680 the conserved β-catenin (BAR-1) pathway 642:680 the conserved β-catenin (BAR-1) pathway 642:680 Genetic interaction studies revealed that nutrient-responsive OGT-1 acts through the conserved β-catenin (BAR-1) pathway and in concert with p38 MAPK (PMK-1) to modulate the immune response to S. aureus. 25474640 0 26 theme sensor 19:24 arg1 transferase 35:45 Conserved nutrient sensor O-GlcNAc transferase 0:45 Conserved nutrient sensor O-GlcNAc transferase 0:45 Conserved nutrient sensor O-GlcNAc transferase is integral to C. elegans pathogen-specific immunity. 25474640 4 27 theme interaction 569:579 arg1 studies 581:587 Genetic interaction studies 561:587 Genetic interaction studies 561:587 Genetic interaction studies revealed that nutrient-responsive OGT-1 acts through the conserved β-catenin (BAR-1) pathway and in concert with p38 MAPK (PMK-1) to modulate the immune response to S. aureus. 25474640 0 28 dep C. 62:63 arg1 pathogen-specific 73:89 pathogen-specific 73:89 pathogen-specific 73:89 Conserved nutrient sensor O-GlcNAc transferase is integral to C. elegans pathogen-specific immunity. 25474640 0 28 dep C. 62:63 arg1 elegans 65:71 elegans 65:71 elegans 65:71 Conserved nutrient sensor O-GlcNAc transferase is integral to C. elegans pathogen-specific immunity. 25474640 4 29 theme conserved 646:654 arg1 pathway 674:680 the conserved β-catenin (BAR-1) pathway 642:680 the conserved β-catenin (BAR-1) pathway 642:680 Genetic interaction studies revealed that nutrient-responsive OGT-1 acts through the conserved β-catenin (BAR-1) pathway and in concert with p38 MAPK (PMK-1) to modulate the immune response to S. aureus. 25474640 2 30 from defective 229:237 arg1 enzymes 246:252 the enzymes 242:252 the enzymes of O-linked N-acetylglucosamine (O-GlcNAc) cycling 242:303 Using mutants defective in the enzymes of O-linked N-acetylglucosamine (O-GlcNAc) cycling, we examined the role of this nutrient-sensing pathway in the C. elegans innate immune response. 25474640 6 31 theme immunity 972:979 arg1 module 981:986 an immunity module 969:986 an immunity module evolutionarily conserved from C. elegans to humans 969:1037 The participation of nutrient sensor OGT-1 in an immunity module evolutionarily conserved from C. elegans to humans reveals an unexplored nexus between nutrient availability and a pathogen-specific immune response. 25474640 1 32 theme elegans 197:203 arg1 immunity 205:212 Caenorhabidits elegans immunity 182:212 Caenorhabidits elegans immunity 182:212 Discriminating pathogenic bacteria from bacteria used as a food source is key to Caenorhabidits elegans immunity. 25474640 6 33 theme immune 1121:1126 arg1 response 1128:1135 a pathogen-specific immune response 1101:1135 a pathogen-specific immune response 1101:1135 The participation of nutrient sensor OGT-1 in an immunity module evolutionarily conserved from C. elegans to humans reveals an unexplored nexus between nutrient availability and a pathogen-specific immune response. 25474640 5 34 theme unique 879:884 arg1 genes 916:920 unique stress- and immune-responsive genes 879:920 unique stress- and immune-responsive genes 879:920 Moreover, whole genome transcriptional profiling revealed that O-GlcNAc cycling mutants exhibited deregulation of unique stress- and immune-responsive genes. 25474640 6 35 theme nutrient 1075:1082 arg1 availability 1084:1095 nutrient availability 1075:1095 nutrient availability 1075:1095 The participation of nutrient sensor OGT-1 in an immunity module evolutionarily conserved from C. elegans to humans reveals an unexplored nexus between nutrient availability and a pathogen-specific immune response. 25474640 3 36 theme Genetic 402:408 arg1 analysis 410:417 Genetic analysis 402:417 Genetic analysis 402:417 Genetic analysis showed that deletion of O-GlcNAc transferase (ogt-1) yielded animals hypersensitive to the human pathogen S. aureus but not to P. aeruginosa. 25474640 2 37 theme pathway 352:358 arg1 role 322:325 the role 318:325 the role of this nutrient-sensing pathway in the C. elegans innate immune response 318:399 Using mutants defective in the enzymes of O-linked N-acetylglucosamine (O-GlcNAc) cycling, we examined the role of this nutrient-sensing pathway in the C. elegans innate immune response. 25474640 5 38 theme genome 781:786 arg1 profiling 804:812 whole genome transcriptional profiling 775:812 whole genome transcriptional profiling 775:812 Moreover, whole genome transcriptional profiling revealed that O-GlcNAc cycling mutants exhibited deregulation of unique stress- and immune-responsive genes. 25474640 6 39 theme OGT-1 960:964 arg1 participation 927:939 The participation 923:939 The participation of nutrient sensor OGT-1 in an immunity module evolutionarily conserved from C. elegans to humans 923:1037 The participation of nutrient sensor OGT-1 in an immunity module evolutionarily conserved from C. elegans to humans reveals an unexplored nexus between nutrient availability and a pathogen-specific immune response. 25474640 2 40 theme defective 229:237 arg1 mutants 221:227 mutants 221:227 mutants defective in the enzymes of O-linked N-acetylglucosamine (O-GlcNAc) cycling 221:303 Using mutants defective in the enzymes of O-linked N-acetylglucosamine (O-GlcNAc) cycling, we examined the role of this nutrient-sensing pathway in the C. elegans innate immune response. 25474640 2 41 theme nutrient-sensing 335:350 arg1 pathway 352:358 this nutrient-sensing pathway 330:358 this nutrient-sensing pathway 330:358 Using mutants defective in the enzymes of O-linked N-acetylglucosamine (O-GlcNAc) cycling, we examined the role of this nutrient-sensing pathway in the C. elegans innate immune response. 25474640 6 42 theme sensor 953:958 arg1 OGT-1 960:964 nutrient sensor OGT-1 944:964 nutrient sensor OGT-1 944:964 The participation of nutrient sensor OGT-1 in an immunity module evolutionarily conserved from C. elegans to humans reveals an unexplored nexus between nutrient availability and a pathogen-specific immune response. 25474640 5 43 theme whole 775:779 arg1 profiling 804:812 whole genome transcriptional profiling 775:812 whole genome transcriptional profiling 775:812 Moreover, whole genome transcriptional profiling revealed that O-GlcNAc cycling mutants exhibited deregulation of unique stress- and immune-responsive genes. 25474640 5 44 theme stress- 886:892 arg1 genes 916:920 unique stress- and immune-responsive genes 879:920 unique stress- and immune-responsive genes 879:920 Moreover, whole genome transcriptional profiling revealed that O-GlcNAc cycling mutants exhibited deregulation of unique stress- and immune-responsive genes. 25474640 6 45 theme unexplored 1050:1059 arg1 nexus 1061:1065 an unexplored nexus 1047:1065 an unexplored nexus between nutrient availability and a pathogen-specific immune response 1047:1135 The participation of nutrient sensor OGT-1 in an immunity module evolutionarily conserved from C. elegans to humans reveals an unexplored nexus between nutrient availability and a pathogen-specific immune response. 25474640 2 46 theme N-acetylglucosamine 266:284 arg1 cycling 297:303 O-linked N-acetylglucosamine (O-GlcNAc) cycling 257:303 O-linked N-acetylglucosamine (O-GlcNAc) cycling 257:303 Using mutants defective in the enzymes of O-linked N-acetylglucosamine (O-GlcNAc) cycling, we examined the role of this nutrient-sensing pathway in the C. elegans innate immune response. 25474640 1 47 theme food 160:163 arg1 source 165:170 a food source 158:170 a food source 158:170 Discriminating pathogenic bacteria from bacteria used as a food source is key to Caenorhabidits elegans immunity. 25474640 6 48 from participation 927:939 arg1 module 981:986 an immunity module 969:986 an immunity module evolutionarily conserved from C. elegans to humans 969:1037 The participation of nutrient sensor OGT-1 in an immunity module evolutionarily conserved from C. elegans to humans reveals an unexplored nexus between nutrient availability and a pathogen-specific immune response. 25474640 2 49 theme O-linked 257:264 arg1 O-GlcNAc 287:294 O-GlcNAc 287:294 O-GlcNAc 287:294 Using mutants defective in the enzymes of O-linked N-acetylglucosamine (O-GlcNAc) cycling, we examined the role of this nutrient-sensing pathway in the C. elegans innate immune response. 25474640 2 49 theme O-linked 257:264 arg1 N-acetylglucosamine 266:284 O-linked N-acetylglucosamine 257:284 O-linked N-acetylglucosamine (O-GlcNAc) cycling 257:303 Using mutants defective in the enzymes of O-linked N-acetylglucosamine (O-GlcNAc) cycling, we examined the role of this nutrient-sensing pathway in the C. elegans innate immune response. 25474640 5 50 theme O-GlcNAc 828:835 arg1 mutants 845:851 O-GlcNAc cycling mutants 828:851 O-GlcNAc cycling mutants 828:851 Moreover, whole genome transcriptional profiling revealed that O-GlcNAc cycling mutants exhibited deregulation of unique stress- and immune-responsive genes. 25474640 6 51 theme pathogen-specific 1103:1119 arg1 response 1128:1135 a pathogen-specific immune response 1101:1135 a pathogen-specific immune response 1101:1135 The participation of nutrient sensor OGT-1 in an immunity module evolutionarily conserved from C. elegans to humans reveals an unexplored nexus between nutrient availability and a pathogen-specific immune response. 25474640 0 52 theme C. 62:63 arg1 immunity 91:98 C. elegans pathogen-specific immunity 62:98 C. elegans pathogen-specific immunity 62:98 Conserved nutrient sensor O-GlcNAc transferase is integral to C. elegans pathogen-specific immunity. 25474640 6 53 theme nutrient 944:951 arg1 OGT-1 960:964 nutrient sensor OGT-1 944:964 nutrient sensor OGT-1 944:964 The participation of nutrient sensor OGT-1 in an immunity module evolutionarily conserved from C. elegans to humans reveals an unexplored nexus between nutrient availability and a pathogen-specific immune response. 25474640 2 54 theme C. 367:368 arg1 response 392:399 the C. elegans innate immune response 363:399 the C. elegans innate immune response 363:399 Using mutants defective in the enzymes of O-linked N-acetylglucosamine (O-GlcNAc) cycling, we examined the role of this nutrient-sensing pathway in the C. elegans innate immune response. 25305670 7 0 theme elevated 1019:1026 arg1 levels 1041:1046 elevated triglyceride levels 1019:1046 elevated triglyceride levels 1019:1046 CONCLUSIONS Our study indicates that the 1-deoxySL formation is not per-se caused by hyperglycemia but rather specifically associated with metabolic changes in T2DM, such as elevated triglyceride levels. 25305670 2 1 with patients 295:302 arg1 MetS 329:332 MetS 329:332 MetS 329:332 Recently we reported significant elevations of 1-deoxysphingolipids (1-deoxySL) - an atypical class of sphingolipids in patients with metabolic syndrome (MetS) and diabetes type 2 (T2DM). 25305670 2 1 with patients 295:302 arg1 diabetes 339:346 diabetes type 2 339:353 diabetes type 2 (T2DM) 339:360 Recently we reported significant elevations of 1-deoxysphingolipids (1-deoxySL) - an atypical class of sphingolipids in patients with metabolic syndrome (MetS) and diabetes type 2 (T2DM). 25305670 2 1 with patients 295:302 arg1 syndrome 319:326 metabolic syndrome 309:326 metabolic syndrome (MetS) 309:333 Recently we reported significant elevations of 1-deoxysphingolipids (1-deoxySL) - an atypical class of sphingolipids in patients with metabolic syndrome (MetS) and diabetes type 2 (T2DM). 25305670 2 1 with patients 295:302 arg1 T2DM 356:359 T2DM 356:359 T2DM 356:359 Recently we reported significant elevations of 1-deoxysphingolipids (1-deoxySL) - an atypical class of sphingolipids in patients with metabolic syndrome (MetS) and diabetes type 2 (T2DM). 25305670 7 2 theme triglyceride 1028:1039 arg1 levels 1041:1046 elevated triglyceride levels 1019:1046 elevated triglyceride levels 1019:1046 CONCLUSIONS Our study indicates that the 1-deoxySL formation is not per-se caused by hyperglycemia but rather specifically associated with metabolic changes in T2DM, such as elevated triglyceride levels. 25305670 1 3 theme insulin 142:148 arg1 resistance 150:159 insulin resistance 142:159 insulin resistance 142:159 BACKGROUND Sphingolipids are increasingly recognized to play a role in insulin resistance and diabetes. 25305670 6 4 theme 1-deoxSL 803:810 arg1 levels 812:817 1-deoxSL levels 803:817 1-deoxSL levels 803:817 In contrast to patients with T2DM, 1-deoxSL levels are not elevated in T1DM. 25305670 2 5 dep diabetes 339:346 arg1 type 348:351 type 2 348:353 diabetes type 2 (T2DM) 339:360 Recently we reported significant elevations of 1-deoxysphingolipids (1-deoxySL) - an atypical class of sphingolipids in patients with metabolic syndrome (MetS) and diabetes type 2 (T2DM). 25305670 4 6 theme N-acyl 539:544 arg1 headgroups 559:568 the N-acyl and O-linked headgroups 535:568 the N-acyl and O-linked headgroups in plasma from individuals with T1DM (N = 27), T2DM (N = 30) and healthy controls (N = 23) 535:659 FINDINGS We analyzed the long chain base profile by LC-MS after hydrolyzing the N-acyl and O-linked headgroups in plasma from individuals with T1DM (N = 27), T2DM (N = 30) and healthy controls (N = 23). 25305670 7 7 theme 1-deoxySL 886:894 arg1 formation 896:904 the 1-deoxySL formation 882:904 the 1-deoxySL formation 882:904 CONCLUSIONS Our study indicates that the 1-deoxySL formation is not per-se caused by hyperglycemia but rather specifically associated with metabolic changes in T2DM, such as elevated triglyceride levels. 25305670 2 8 theme atypical 260:267 arg1 class 269:273 an atypical class 257:273 1-deoxysphingolipids (1-deoxySL) - an atypical class of sphingolipids in patients with metabolic syndrome (MetS) and diabetes type 2 (T2DM) 222:360 Recently we reported significant elevations of 1-deoxysphingolipids (1-deoxySL) - an atypical class of sphingolipids in patients with metabolic syndrome (MetS) and diabetes type 2 (T2DM). 25305670 0 9 theme sphingoid 8:16 arg1 profiles 23:30 Altered sphingoid base profiles 0:30 Altered sphingoid base profiles in type 1 0:40 Altered sphingoid base profiles in type 1 compared to type 2 diabetes. 25305670 2 10 theme metabolic 309:317 arg1 MetS 329:332 MetS 329:332 MetS 329:332 Recently we reported significant elevations of 1-deoxysphingolipids (1-deoxySL) - an atypical class of sphingolipids in patients with metabolic syndrome (MetS) and diabetes type 2 (T2DM). 25305670 2 10 theme metabolic 309:317 arg1 syndrome 319:326 metabolic syndrome 309:326 metabolic syndrome (MetS) 309:333 Recently we reported significant elevations of 1-deoxysphingolipids (1-deoxySL) - an atypical class of sphingolipids in patients with metabolic syndrome (MetS) and diabetes type 2 (T2DM). 25305670 0 11 theme Altered 0:6 arg1 profiles 23:30 Altered sphingoid base profiles 0:30 Altered sphingoid base profiles in type 1 0:40 Altered sphingoid base profiles in type 1 compared to type 2 diabetes. 25305670 7 12 from changes 994:1000 arg1 T2DM 1005:1008 T2DM 1005:1008 T2DM 1005:1008 CONCLUSIONS Our study indicates that the 1-deoxySL formation is not per-se caused by hyperglycemia but rather specifically associated with metabolic changes in T2DM, such as elevated triglyceride levels. 25305670 1 13 theme BACKGROUND 71:80 arg1 Sphingolipids 82:94 BACKGROUND Sphingolipids 71:94 BACKGROUND Sphingolipids 71:94 BACKGROUND Sphingolipids are increasingly recognized to play a role in insulin resistance and diabetes. 25305670 4 14 theme base 495:498 arg1 profile 500:506 the long chain base profile 480:506 the long chain base profile by LC-MS 480:515 FINDINGS We analyzed the long chain base profile by LC-MS after hydrolyzing the N-acyl and O-linked headgroups in plasma from individuals with T1DM (N = 27), T2DM (N = 30) and healthy controls (N = 23). 25305670 4 15 from individuals 585:595 arg1 plasma 573:578 plasma 573:578 plasma from individuals with T1DM (N = 27), T2DM (N = 30) and healthy controls (N = 23) 573:659 FINDINGS We analyzed the long chain base profile by LC-MS after hydrolyzing the N-acyl and O-linked headgroups in plasma from individuals with T1DM (N = 27), T2DM (N = 30) and healthy controls (N = 23). 25305670 4 15 from individuals 585:595 arg1 headgroups 559:568 the N-acyl and O-linked headgroups 535:568 the N-acyl and O-linked headgroups in plasma from individuals with T1DM (N = 27), T2DM (N = 30) and healthy controls (N = 23) 535:659 FINDINGS We analyzed the long chain base profile by LC-MS after hydrolyzing the N-acyl and O-linked headgroups in plasma from individuals with T1DM (N = 27), T2DM (N = 30) and healthy controls (N = 23). 25305670 0 16 theme base 18:21 arg1 profiles 23:30 Altered sphingoid base profiles 0:30 Altered sphingoid base profiles in type 1 0:40 Altered sphingoid base profiles in type 1 compared to type 2 diabetes. 25305670 7 17 theme metabolic 984:992 arg1 changes 994:1000 metabolic changes 984:1000 metabolic changes 984:1000 CONCLUSIONS Our study indicates that the 1-deoxySL formation is not per-se caused by hyperglycemia but rather specifically associated with metabolic changes in T2DM, such as elevated triglyceride levels. 25305670 7 17 theme metabolic 984:992 arg1 levels 1041:1046 elevated triglyceride levels 1019:1046 elevated triglyceride levels 1019:1046 CONCLUSIONS Our study indicates that the 1-deoxySL formation is not per-se caused by hyperglycemia but rather specifically associated with metabolic changes in T2DM, such as elevated triglyceride levels. 25305670 3 18 theme diabetes 412:419 arg1 type 421:424 diabetes type 1 412:426 diabetes type 1 (T1DM) 412:433 It is unknown whether 1-deoxySL in patients with diabetes type 1 (T1DM) are similarly elevated. 25305670 3 18 theme diabetes 412:419 arg1 T1DM 429:432 T1DM 429:432 T1DM 429:432 It is unknown whether 1-deoxySL in patients with diabetes type 1 (T1DM) are similarly elevated. 25305670 7 19 dep CONCLUSIONS 845:855 arg1 indicates 867:875 indicates 867:875 indicates that the 1-deoxySL formation is not per-se caused by hyperglycemia but rather specifically associated with metabolic changes in T2DM, such as elevated triglyceride levels 867:1046 CONCLUSIONS Our study indicates that the 1-deoxySL formation is not per-se caused by hyperglycemia but rather specifically associated with metabolic changes in T2DM, such as elevated triglyceride levels. 25305670 4 20 link O-linked 550:557 arg1 headgroups 559:568 the N-acyl and O-linked headgroups 535:568 the N-acyl and O-linked headgroups in plasma from individuals with T1DM (N = 27), T2DM (N = 30) and healthy controls (N = 23) 535:659 FINDINGS We analyzed the long chain base profile by LC-MS after hydrolyzing the N-acyl and O-linked headgroups in plasma from individuals with T1DM (N = 27), T2DM (N = 30) and healthy controls (N = 23). 25305670 2 21 theme 1-deoxysphingolipids 222:241 arg1 elevations 208:217 significant elevations 196:217 significant elevations of 1-deoxysphingolipids (1-deoxySL) - an atypical class of sphingolipids in patients with metabolic syndrome (MetS) and diabetes type 2 (T2DM) 196:360 Recently we reported significant elevations of 1-deoxysphingolipids (1-deoxySL) - an atypical class of sphingolipids in patients with metabolic syndrome (MetS) and diabetes type 2 (T2DM). 25305670 2 22 dep 1-deoxysphingolipids 222:241 arg1 class 269:273 an atypical class 257:273 1-deoxysphingolipids (1-deoxySL) - an atypical class of sphingolipids in patients with metabolic syndrome (MetS) and diabetes type 2 (T2DM) 222:360 Recently we reported significant elevations of 1-deoxysphingolipids (1-deoxySL) - an atypical class of sphingolipids in patients with metabolic syndrome (MetS) and diabetes type 2 (T2DM). 25305670 4 23 dep FINDINGS 459:466 arg1 analyzed 471:478 analyzed 471:478 analyzed the long chain base profile by LC-MS after hydrolyzing the N-acyl and O-linked headgroups in plasma from individuals with T1DM (N = 27), T2DM (N = 30) and healthy controls (N = 23) 471:659 FINDINGS We analyzed the long chain base profile by LC-MS after hydrolyzing the N-acyl and O-linked headgroups in plasma from individuals with T1DM (N = 27), T2DM (N = 30) and healthy controls (N = 23). 25305670 4 24 theme chain 489:493 arg1 profile 500:506 the long chain base profile 480:506 the long chain base profile by LC-MS 480:515 FINDINGS We analyzed the long chain base profile by LC-MS after hydrolyzing the N-acyl and O-linked headgroups in plasma from individuals with T1DM (N = 27), T2DM (N = 30) and healthy controls (N = 23). 25305670 2 25 theme significant 196:206 arg1 elevations 208:217 significant elevations 196:217 significant elevations of 1-deoxysphingolipids (1-deoxySL) - an atypical class of sphingolipids in patients with metabolic syndrome (MetS) and diabetes type 2 (T2DM) 196:360 Recently we reported significant elevations of 1-deoxysphingolipids (1-deoxySL) - an atypical class of sphingolipids in patients with metabolic syndrome (MetS) and diabetes type 2 (T2DM). 25305670 2 26 from class 269:273 arg1 patients 295:302 patients 295:302 patients with metabolic syndrome (MetS) and diabetes type 2 (T2DM) 295:360 Recently we reported significant elevations of 1-deoxysphingolipids (1-deoxySL) - an atypical class of sphingolipids in patients with metabolic syndrome (MetS) and diabetes type 2 (T2DM). 25305670 4 27 theme long 484:487 arg1 profile 500:506 the long chain base profile 480:506 the long chain base profile by LC-MS 480:515 FINDINGS We analyzed the long chain base profile by LC-MS after hydrolyzing the N-acyl and O-linked headgroups in plasma from individuals with T1DM (N = 27), T2DM (N = 30) and healthy controls (N = 23). 25305670 3 28 with patients 398:405 arg1 type 421:424 diabetes type 1 412:426 diabetes type 1 (T1DM) 412:433 It is unknown whether 1-deoxySL in patients with diabetes type 1 (T1DM) are similarly elevated. 25305670 3 28 with patients 398:405 arg1 T1DM 429:432 T1DM 429:432 T1DM 429:432 It is unknown whether 1-deoxySL in patients with diabetes type 1 (T1DM) are similarly elevated. 25305670 4 29 with individuals 585:595 arg1 controls 643:650 healthy controls 635:650 healthy controls (N = 23) 635:659 FINDINGS We analyzed the long chain base profile by LC-MS after hydrolyzing the N-acyl and O-linked headgroups in plasma from individuals with T1DM (N = 27), T2DM (N = 30) and healthy controls (N = 23). 25305670 4 29 with individuals 585:595 arg1 T2DM 617:620 T2DM 617:620 T2DM (N = 30) 617:629 FINDINGS We analyzed the long chain base profile by LC-MS after hydrolyzing the N-acyl and O-linked headgroups in plasma from individuals with T1DM (N = 27), T2DM (N = 30) and healthy controls (N = 23). 25305670 4 29 with individuals 585:595 arg1 N = 30 623:628 N = 30 623:628 N = 30 623:628 FINDINGS We analyzed the long chain base profile by LC-MS after hydrolyzing the N-acyl and O-linked headgroups in plasma from individuals with T1DM (N = 27), T2DM (N = 30) and healthy controls (N = 23). 25305670 4 29 with individuals 585:595 arg1 N = 23 653:658 N = 23 653:658 N = 23 653:658 FINDINGS We analyzed the long chain base profile by LC-MS after hydrolyzing the N-acyl and O-linked headgroups in plasma from individuals with T1DM (N = 27), T2DM (N = 30) and healthy controls (N = 23). 25305670 4 29 with individuals 585:595 arg1 T1DM 602:605 T1DM 602:605 T1DM (N = 27) 602:614 FINDINGS We analyzed the long chain base profile by LC-MS after hydrolyzing the N-acyl and O-linked headgroups in plasma from individuals with T1DM (N = 27), T2DM (N = 30) and healthy controls (N = 23). 25305670 4 29 with individuals 585:595 arg1 N = 27 608:613 N = 27 608:613 N = 27 608:613 FINDINGS We analyzed the long chain base profile by LC-MS after hydrolyzing the N-acyl and O-linked headgroups in plasma from individuals with T1DM (N = 27), T2DM (N = 30) and healthy controls (N = 23). 25305670 4 30 theme O-linked 550:557 arg1 headgroups 559:568 the N-acyl and O-linked headgroups 535:568 the N-acyl and O-linked headgroups in plasma from individuals with T1DM (N = 27), T2DM (N = 30) and healthy controls (N = 23) 535:659 FINDINGS We analyzed the long chain base profile by LC-MS after hydrolyzing the N-acyl and O-linked headgroups in plasma from individuals with T1DM (N = 27), T2DM (N = 30) and healthy controls (N = 23). 25305670 2 31 theme sphingolipids 278:290 arg1 class 269:273 an atypical class 257:273 1-deoxysphingolipids (1-deoxySL) - an atypical class of sphingolipids in patients with metabolic syndrome (MetS) and diabetes type 2 (T2DM) 222:360 Recently we reported significant elevations of 1-deoxysphingolipids (1-deoxySL) - an atypical class of sphingolipids in patients with metabolic syndrome (MetS) and diabetes type 2 (T2DM). 25305670 3 32 from 1-deoxySL 385:393 arg1 patients 398:405 patients 398:405 patients with diabetes type 1 (T1DM) 398:433 It is unknown whether 1-deoxySL in patients with diabetes type 1 (T1DM) are similarly elevated. 25305670 4 33 theme healthy 635:641 arg1 N = 23 653:658 N = 23 653:658 N = 23 653:658 FINDINGS We analyzed the long chain base profile by LC-MS after hydrolyzing the N-acyl and O-linked headgroups in plasma from individuals with T1DM (N = 27), T2DM (N = 30) and healthy controls (N = 23). 25305670 4 33 theme healthy 635:641 arg1 controls 643:650 healthy controls 635:650 healthy controls (N = 23) 635:659 FINDINGS We analyzed the long chain base profile by LC-MS after hydrolyzing the N-acyl and O-linked headgroups in plasma from individuals with T1DM (N = 27), T2DM (N = 30) and healthy controls (N = 23). 25305670 6 34 dep patients 783:790 arg1 contrast 771:778 contrast 771:778 contrast 771:778 In contrast to patients with T2DM, 1-deoxSL levels are not elevated in T1DM. 25305670 0 35 theme type 54:57 arg1 diabetes 61:68 type 2 diabetes 54:68 type 2 diabetes 54:68 Altered sphingoid base profiles in type 1 compared to type 2 diabetes. 25305670 4 36 from headgroups 559:568 arg1 individuals 585:595 individuals 585:595 individuals with T1DM (N = 27), T2DM (N = 30) and healthy controls (N = 23) 585:659 FINDINGS We analyzed the long chain base profile by LC-MS after hydrolyzing the N-acyl and O-linked headgroups in plasma from individuals with T1DM (N = 27), T2DM (N = 30) and healthy controls (N = 23). 25305670 4 36 from headgroups 559:568 arg1 plasma 573:578 plasma 573:578 plasma from individuals with T1DM (N = 27), T2DM (N = 30) and healthy controls (N = 23) 573:659 FINDINGS We analyzed the long chain base profile by LC-MS after hydrolyzing the N-acyl and O-linked headgroups in plasma from individuals with T1DM (N = 27), T2DM (N = 30) and healthy controls (N = 23). 25305670 0 37 from profiles 23:30 arg1 type 35:38 type 1 35:40 type 1 35:40 Altered sphingoid base profiles in type 1 compared to type 2 diabetes. 25305670 6 38 with patients 783:790 arg1 T2DM 797:800 T2DM 797:800 T2DM 797:800 In contrast to patients with T2DM, 1-deoxSL levels are not elevated in T1DM. 24474760 6 0 theme methylation 830:840 arg1 products 842:849 other H3 methylation products 821:849 other H3 methylation products 821:849 We found that the level of H3K27me3, but not other H3 methylation products, was greatly reduced upon OGT depletion. 24474760 4 1 theme repressive 637:646 arg1 complex 648:654 polycomb repressive complex 2 628:656 the polycomb repressive complex 2 (PRC2) 624:663 Here we show that OGT is required for the trimethylation of histone 3 at K27 to form the product H3K27me3, a process catalyzed by the histone methyltransferase enhancer of zeste homolog 2 (EZH2) in the polycomb repressive complex 2 (PRC2). 24474760 4 1 theme repressive 637:646 arg1 PRC2 659:662 PRC2 659:662 PRC2 659:662 Here we show that OGT is required for the trimethylation of histone 3 at K27 to form the product H3K27me3, a process catalyzed by the histone methyltransferase enhancer of zeste homolog 2 (EZH2) in the polycomb repressive complex 2 (PRC2). 24474760 9 2 from reduction 1315:1323 arg1 stability 1328:1336 stability 1328:1336 stability 1328:1336 Importantly, we identified that serine 75 is the site for EZH2 O-GlcNAcylation, and the EZH2 mutant S75A exhibited reduction in stability. 24474760 8 3 theme OGT 1111:1113 arg1 interaction 1096:1106 the interaction 1092:1106 the interaction of OGT and EZH2/PRC2 1092:1127 Furthermore, the interaction of OGT and EZH2/PRC2 was detected by coimmunoprecipitation and cosedimentation experiments. 24474760 4 4 theme histone 486:492 arg1 trimethylation 468:481 the trimethylation 464:481 the trimethylation of histone 3 at K27 to form the product H3K27me3, a process catalyzed by the histone methyltransferase enhancer of zeste homolog 2 (EZH2) in the polycomb repressive complex 2 (PRC2) 464:663 Here we show that OGT is required for the trimethylation of histone 3 at K27 to form the product H3K27me3, a process catalyzed by the histone methyltransferase enhancer of zeste homolog 2 (EZH2) in the polycomb repressive complex 2 (PRC2). 24474760 10 5 theme ChIP 1363:1366 arg1 analysis 1368:1375 ChIP analysis 1363:1375 ChIP analysis 1363:1375 Finally, microarray and ChIP analysis have characterized a specific subset of potential tumor suppressor genes subject to repression via the OGT-EZH2 axis. 24474760 4 6 theme polycomb 628:635 arg1 complex 648:654 polycomb repressive complex 2 628:656 the polycomb repressive complex 2 (PRC2) 624:663 Here we show that OGT is required for the trimethylation of histone 3 at K27 to form the product H3K27me3, a process catalyzed by the histone methyltransferase enhancer of zeste homolog 2 (EZH2) in the polycomb repressive complex 2 (PRC2). 24474760 4 6 theme polycomb 628:635 arg1 PRC2 659:662 PRC2 659:662 PRC2 659:662 Here we show that OGT is required for the trimethylation of histone 3 at K27 to form the product H3K27me3, a process catalyzed by the histone methyltransferase enhancer of zeste homolog 2 (EZH2) in the polycomb repressive complex 2 (PRC2). 24474760 6 7 theme other 821:825 arg1 products 842:849 other H3 methylation products 821:849 other H3 methylation products 821:849 We found that the level of H3K27me3, but not other H3 methylation products, was greatly reduced upon OGT depletion. 24474760 4 8 from trimethylation 468:481 arg1 K27 499:501 K27 499:501 K27 499:501 Here we show that OGT is required for the trimethylation of histone 3 at K27 to form the product H3K27me3, a process catalyzed by the histone methyltransferase enhancer of zeste homolog 2 (EZH2) in the polycomb repressive complex 2 (PRC2). 24474760 2 9 theme epigenetic 276:285 arg1 regulation 287:296 transcriptional and epigenetic regulation 256:296 transcriptional and epigenetic regulation 256:296 OGT participates in transcriptional and epigenetic regulation, and dysregulation of OGT has been implicated in diseases such as cancer. 24474760 11 10 theme OGT-mediated 1532:1543 arg1 O-GlcNAcylation 1545:1559 OGT-mediated O-GlcNAcylation 1532:1559 OGT-mediated O-GlcNAcylation at S75 1532:1566 Together these results indicate that OGT-mediated O-GlcNAcylation at S75 stabilizes EZH2 and hence facilitates the formation of H3K27me3. 24474760 1 11 theme N-acetylglucosamine 72:90 arg1 transferase 101:111 O-linked N-acetylglucosamine (GlcNAc) transferase 63:111 O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) 63:117 O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) is the only known enzyme that catalyzes the O-GlcNAcylation of proteins at the Ser or Thr side chain hydroxyl group. 24474760 1 11 theme N-acetylglucosamine 72:90 arg1 enzyme 137:142 the only known enzyme 122:142 the only known enzyme that catalyzes the O-GlcNAcylation of proteins at the Ser or Thr side chain hydroxyl group 122:233 O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) is the only known enzyme that catalyzes the O-GlcNAcylation of proteins at the Ser or Thr side chain hydroxyl group. 24474760 1 11 theme N-acetylglucosamine 72:90 arg1 OGT 114:116 OGT 114:116 OGT 114:116 O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) is the only known enzyme that catalyzes the O-GlcNAcylation of proteins at the Ser or Thr side chain hydroxyl group. 24474760 1 12 link O-linked 63:70 arg1 GlcNAc 93:98 GlcNAc 93:98 GlcNAc 93:98 O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) is the only known enzyme that catalyzes the O-GlcNAcylation of proteins at the Ser or Thr side chain hydroxyl group. 24474760 1 12 link O-linked 63:70 arg1 N-acetylglucosamine 72:90 O-linked N-acetylglucosamine 63:90 O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) 63:117 O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) is the only known enzyme that catalyzes the O-GlcNAcylation of proteins at the Ser or Thr side chain hydroxyl group. 24474760 9 13 dep mutant 1293:1298 arg1 S75A 1300:1303 S75A 1300:1303 S75A 1300:1303 Importantly, we identified that serine 75 is the site for EZH2 O-GlcNAcylation, and the EZH2 mutant S75A exhibited reduction in stability. 24474760 10 14 theme specific 1398:1405 arg1 subset 1407:1412 a specific subset 1396:1412 a specific subset of potential tumor suppressor genes subject to repression via the OGT-EZH2 axis 1396:1492 Finally, microarray and ChIP analysis have characterized a specific subset of potential tumor suppressor genes subject to repression via the OGT-EZH2 axis. 24474760 2 15 theme transcriptional 256:270 arg1 regulation 287:296 transcriptional and epigenetic regulation 256:296 transcriptional and epigenetic regulation 256:296 OGT participates in transcriptional and epigenetic regulation, and dysregulation of OGT has been implicated in diseases such as cancer. 24474760 11 16 from S75 1564:1566 arg1 O-GlcNAcylation 1545:1559 OGT-mediated O-GlcNAcylation 1532:1559 OGT-mediated O-GlcNAcylation at S75 1532:1566 Together these results indicate that OGT-mediated O-GlcNAcylation at S75 stabilizes EZH2 and hence facilitates the formation of H3K27me3. 24474760 12 17 theme OGT 1758:1760 arg1 role 1750:1753 a unique epigenetic role 1730:1753 a unique epigenetic role of OGT in regulating histone methylation 1730:1794 The study not only uncovers a functional posttranslational modification of EZH2 but also reveals a unique epigenetic role of OGT in regulating histone methylation. 24474760 5 18 theme important 694:702 arg1 modifications 712:724 the most important histone modifications 685:724 the most important histone modifications 685:724 H3K27me3 is one of the most important histone modifications to mark the transcriptionally silenced chromatin. 24474760 6 19 theme H3K27me3 803:810 arg1 level 794:798 the level 790:798 the level of H3K27me3, but not other H3 methylation products, 790:850 We found that the level of H3K27me3, but not other H3 methylation products, was greatly reduced upon OGT depletion. 24474760 7 20 theme demethylases 1002:1013 arg1 levels 986:991 the levels 982:991 the levels of H3K27 demethylases UTX and JMJD3 982:1027 OGT knockdown specifically down-regulated the protein stability of EZH2, without altering the levels of H3K27 demethylases UTX and JMJD3, and disrupted the integrity of the PRC2 complex. 24474760 10 21 theme OGT-EZH2 1480:1487 arg1 axis 1489:1492 the OGT-EZH2 axis 1476:1492 the OGT-EZH2 axis 1476:1492 Finally, microarray and ChIP analysis have characterized a specific subset of potential tumor suppressor genes subject to repression via the OGT-EZH2 axis. 24474760 11 22 theme H3K27me3 1623:1630 arg1 formation 1610:1618 the formation 1606:1618 the formation of H3K27me3 1606:1630 Together these results indicate that OGT-mediated O-GlcNAcylation at S75 stabilizes EZH2 and hence facilitates the formation of H3K27me3. 24474760 8 23 theme cosedimentation 1171:1185 arg1 experiments 1187:1197 cosedimentation experiments 1171:1197 cosedimentation experiments 1171:1197 Furthermore, the interaction of OGT and EZH2/PRC2 was detected by coimmunoprecipitation and cosedimentation experiments. 24474760 6 24 theme H3 827:828 arg1 products 842:849 other H3 methylation products 821:849 other H3 methylation products 821:849 We found that the level of H3K27me3, but not other H3 methylation products, was greatly reduced upon OGT depletion. 24474760 7 25 theme PRC2 1065:1068 arg1 complex 1070:1076 the PRC2 complex 1061:1076 the PRC2 complex 1061:1076 OGT knockdown specifically down-regulated the protein stability of EZH2, without altering the levels of H3K27 demethylases UTX and JMJD3, and disrupted the integrity of the PRC2 complex. 24474760 12 26 theme EZH2 1708:1711 arg1 modification 1692:1703 a functional posttranslational modification 1661:1703 a functional posttranslational modification of EZH2 1661:1711 The study not only uncovers a functional posttranslational modification of EZH2 but also reveals a unique epigenetic role of OGT in regulating histone methylation. 24474760 1 27 theme proteins 182:189 arg1 O-GlcNAcylation 163:177 the O-GlcNAcylation 159:177 the O-GlcNAcylation of proteins 159:189 O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) is the only known enzyme that catalyzes the O-GlcNAcylation of proteins at the Ser or Thr side chain hydroxyl group. 24474760 0 28 theme protein 31:37 arg1 stability 39:47 EZH2 protein stability 26:47 EZH2 protein stability 26:47 O-GlcNAcylation regulates EZH2 protein stability and function. 24474760 9 29 theme EZH2 1258:1261 arg1 O-GlcNAcylation 1263:1277 EZH2 O-GlcNAcylation 1258:1277 EZH2 O-GlcNAcylation 1258:1277 Importantly, we identified that serine 75 is the site for EZH2 O-GlcNAcylation, and the EZH2 mutant S75A exhibited reduction in stability. 24474760 10 30 theme tumor 1427:1431 arg1 genes 1444:1448 potential tumor suppressor genes 1417:1448 potential tumor suppressor genes subject to repression via the OGT-EZH2 axis 1417:1492 Finally, microarray and ChIP analysis have characterized a specific subset of potential tumor suppressor genes subject to repression via the OGT-EZH2 axis. 24474760 8 31 theme EZH2/PRC2 1119:1127 arg1 interaction 1096:1106 the interaction 1092:1106 the interaction of OGT and EZH2/PRC2 1092:1127 Furthermore, the interaction of OGT and EZH2/PRC2 was detected by coimmunoprecipitation and cosedimentation experiments. 24474760 0 32 theme EZH2 26:29 arg1 stability 39:47 EZH2 protein stability 26:47 EZH2 protein stability 26:47 O-GlcNAcylation regulates EZH2 protein stability and function. 24474760 6 33 theme OGT 877:879 arg1 depletion 881:889 OGT depletion 877:889 OGT depletion 877:889 We found that the level of H3K27me3, but not other H3 methylation products, was greatly reduced upon OGT depletion. 24474760 7 34 theme H3K27 996:1000 arg1 demethylases 1002:1013 H3K27 demethylases UTX and JMJD3 996:1027 H3K27 demethylases UTX and JMJD3 996:1027 OGT knockdown specifically down-regulated the protein stability of EZH2, without altering the levels of H3K27 demethylases UTX and JMJD3, and disrupted the integrity of the PRC2 complex. 24474760 7 34 theme H3K27 996:1000 arg1 JMJD3 1023:1027 JMJD3 1023:1027 JMJD3 1023:1027 OGT knockdown specifically down-regulated the protein stability of EZH2, without altering the levels of H3K27 demethylases UTX and JMJD3, and disrupted the integrity of the PRC2 complex. 24474760 7 34 theme H3K27 996:1000 arg1 UTX 1015:1017 UTX 1015:1017 UTX 1015:1017 OGT knockdown specifically down-regulated the protein stability of EZH2, without altering the levels of H3K27 demethylases UTX and JMJD3, and disrupted the integrity of the PRC2 complex. 24474760 3 35 theme underlying 385:394 arg1 unknown 417:423 unknown 417:423 unknown 417:423 However, the underlying mechanism is largely unknown. 24474760 3 35 theme underlying 385:394 arg1 mechanism 396:404 the underlying mechanism 381:404 the underlying mechanism 381:404 However, the underlying mechanism is largely unknown. 24474760 4 36 theme product 515:521 arg1 process 535:541 a process 533:541 a process catalyzed by the histone methyltransferase enhancer of zeste homolog 2 (EZH2) in the polycomb repressive complex 2 (PRC2) 533:663 Here we show that OGT is required for the trimethylation of histone 3 at K27 to form the product H3K27me3, a process catalyzed by the histone methyltransferase enhancer of zeste homolog 2 (EZH2) in the polycomb repressive complex 2 (PRC2). 24474760 4 36 theme product 515:521 arg1 H3K27me3 523:530 the product H3K27me3 511:530 the product H3K27me3 511:530 Here we show that OGT is required for the trimethylation of histone 3 at K27 to form the product H3K27me3, a process catalyzed by the histone methyltransferase enhancer of zeste homolog 2 (EZH2) in the polycomb repressive complex 2 (PRC2). 24474760 4 37 from enhancer 586:593 arg1 complex 648:654 polycomb repressive complex 2 628:656 the polycomb repressive complex 2 (PRC2) 624:663 Here we show that OGT is required for the trimethylation of histone 3 at K27 to form the product H3K27me3, a process catalyzed by the histone methyltransferase enhancer of zeste homolog 2 (EZH2) in the polycomb repressive complex 2 (PRC2). 24474760 4 37 from enhancer 586:593 arg1 PRC2 659:662 PRC2 659:662 PRC2 659:662 Here we show that OGT is required for the trimethylation of histone 3 at K27 to form the product H3K27me3, a process catalyzed by the histone methyltransferase enhancer of zeste homolog 2 (EZH2) in the polycomb repressive complex 2 (PRC2). 24474760 4 38 theme homolog 604:610 arg1 enhancer 586:593 the histone methyltransferase enhancer 556:593 the histone methyltransferase enhancer of zeste homolog 2 (EZH2) in the polycomb repressive complex 2 (PRC2) 556:663 Here we show that OGT is required for the trimethylation of histone 3 at K27 to form the product H3K27me3, a process catalyzed by the histone methyltransferase enhancer of zeste homolog 2 (EZH2) in the polycomb repressive complex 2 (PRC2). 24474760 4 39 from K27 499:501 arg1 trimethylation 468:481 the trimethylation 464:481 the trimethylation of histone 3 at K27 to form the product H3K27me3, a process catalyzed by the histone methyltransferase enhancer of zeste homolog 2 (EZH2) in the polycomb repressive complex 2 (PRC2) 464:663 Here we show that OGT is required for the trimethylation of histone 3 at K27 to form the product H3K27me3, a process catalyzed by the histone methyltransferase enhancer of zeste homolog 2 (EZH2) in the polycomb repressive complex 2 (PRC2). 24474760 4 39 from K27 499:501 arg1 histone 486:492 histone 3 486:494 histone 3 at K27 to form the product H3K27me3, a process catalyzed by the histone methyltransferase enhancer of zeste homolog 2 (EZH2) in the polycomb repressive complex 2 (PRC2) 486:663 Here we show that OGT is required for the trimethylation of histone 3 at K27 to form the product H3K27me3, a process catalyzed by the histone methyltransferase enhancer of zeste homolog 2 (EZH2) in the polycomb repressive complex 2 (PRC2). 24474760 5 40 theme histone 704:710 arg1 modifications 712:724 the most important histone modifications 685:724 the most important histone modifications 685:724 H3K27me3 is one of the most important histone modifications to mark the transcriptionally silenced chromatin. 24474760 4 41 theme methyltransferase 568:584 arg1 enhancer 586:593 the histone methyltransferase enhancer 556:593 the histone methyltransferase enhancer of zeste homolog 2 (EZH2) in the polycomb repressive complex 2 (PRC2) 556:663 Here we show that OGT is required for the trimethylation of histone 3 at K27 to form the product H3K27me3, a process catalyzed by the histone methyltransferase enhancer of zeste homolog 2 (EZH2) in the polycomb repressive complex 2 (PRC2). 24474760 4 42 theme zeste 598:602 arg1 homolog 604:610 zeste homolog 2 598:612 zeste homolog 2 (EZH2) 598:619 Here we show that OGT is required for the trimethylation of histone 3 at K27 to form the product H3K27me3, a process catalyzed by the histone methyltransferase enhancer of zeste homolog 2 (EZH2) in the polycomb repressive complex 2 (PRC2). 24474760 4 42 theme zeste 598:602 arg1 EZH2 615:618 EZH2 615:618 EZH2 615:618 Here we show that OGT is required for the trimethylation of histone 3 at K27 to form the product H3K27me3, a process catalyzed by the histone methyltransferase enhancer of zeste homolog 2 (EZH2) in the polycomb repressive complex 2 (PRC2). 24474760 5 43 theme modifications 712:724 arg1 modifications 712:724 the most important histone modifications 685:724 the most important histone modifications 685:724 H3K27me3 is one of the most important histone modifications to mark the transcriptionally silenced chromatin. 24474760 5 43 theme modifications 712:724 arg1 one 678:680 one 678:680 one 678:680 H3K27me3 is one of the most important histone modifications to mark the transcriptionally silenced chromatin. 24474760 5 44 theme silenced 756:763 arg1 chromatin 765:773 the transcriptionally silenced chromatin 734:773 the transcriptionally silenced chromatin 734:773 H3K27me3 is one of the most important histone modifications to mark the transcriptionally silenced chromatin. 24474760 10 45 theme genes 1444:1448 arg1 subset 1407:1412 a specific subset 1396:1412 a specific subset of potential tumor suppressor genes subject to repression via the OGT-EZH2 axis 1396:1492 Finally, microarray and ChIP analysis have characterized a specific subset of potential tumor suppressor genes subject to repression via the OGT-EZH2 axis. 24474760 9 46 theme EZH2 1288:1291 arg1 mutant 1293:1298 the EZH2 mutant S75A 1284:1303 the EZH2 mutant S75A 1284:1303 Importantly, we identified that serine 75 is the site for EZH2 O-GlcNAcylation, and the EZH2 mutant S75A exhibited reduction in stability. 24474760 10 47 theme subject 1450:1456 arg1 genes 1444:1448 potential tumor suppressor genes 1417:1448 potential tumor suppressor genes subject to repression via the OGT-EZH2 axis 1417:1492 Finally, microarray and ChIP analysis have characterized a specific subset of potential tumor suppressor genes subject to repression via the OGT-EZH2 axis. 24474760 12 48 theme histone 1776:1782 arg1 methylation 1784:1794 histone methylation 1776:1794 histone methylation 1776:1794 The study not only uncovers a functional posttranslational modification of EZH2 but also reveals a unique epigenetic role of OGT in regulating histone methylation. 24474760 7 49 theme complex 1070:1076 arg1 integrity 1048:1056 the integrity 1044:1056 the integrity of the PRC2 complex 1044:1076 OGT knockdown specifically down-regulated the protein stability of EZH2, without altering the levels of H3K27 demethylases UTX and JMJD3, and disrupted the integrity of the PRC2 complex. 24474760 7 50 theme EZH2 959:962 arg1 stability 946:954 the protein stability 934:954 the protein stability of EZH2 934:962 OGT knockdown specifically down-regulated the protein stability of EZH2, without altering the levels of H3K27 demethylases UTX and JMJD3, and disrupted the integrity of the PRC2 complex. 24474760 1 51 dep Ser 198:200 arg1 the 194:196 the 194:196 the 194:196 O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) is the only known enzyme that catalyzes the O-GlcNAcylation of proteins at the Ser or Thr side chain hydroxyl group. 24474760 1 51 dep Ser 198:200 arg1 group 229:233 side chain hydroxyl group 209:233 side chain hydroxyl group 209:233 O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) is the only known enzyme that catalyzes the O-GlcNAcylation of proteins at the Ser or Thr side chain hydroxyl group. 24474760 7 52 theme protein 938:944 arg1 stability 946:954 the protein stability 934:954 the protein stability of EZH2 934:962 OGT knockdown specifically down-regulated the protein stability of EZH2, without altering the levels of H3K27 demethylases UTX and JMJD3, and disrupted the integrity of the PRC2 complex. 24474760 2 53 theme OGT 320:322 arg1 dysregulation 303:315 dysregulation 303:315 dysregulation of OGT 303:322 OGT participates in transcriptional and epigenetic regulation, and dysregulation of OGT has been implicated in diseases such as cancer. 24474760 10 54 theme suppressor 1433:1442 arg1 genes 1444:1448 potential tumor suppressor genes 1417:1448 potential tumor suppressor genes subject to repression via the OGT-EZH2 axis 1417:1492 Finally, microarray and ChIP analysis have characterized a specific subset of potential tumor suppressor genes subject to repression via the OGT-EZH2 axis. 24474760 1 55 theme O-linked 63:70 arg1 GlcNAc 93:98 GlcNAc 93:98 GlcNAc 93:98 O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) is the only known enzyme that catalyzes the O-GlcNAcylation of proteins at the Ser or Thr side chain hydroxyl group. 24474760 1 55 theme O-linked 63:70 arg1 N-acetylglucosamine 72:90 O-linked N-acetylglucosamine 63:90 O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) 63:117 O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) is the only known enzyme that catalyzes the O-GlcNAcylation of proteins at the Ser or Thr side chain hydroxyl group. 24474760 12 56 theme epigenetic 1739:1748 arg1 role 1750:1753 a unique epigenetic role 1730:1753 a unique epigenetic role of OGT in regulating histone methylation 1730:1794 The study not only uncovers a functional posttranslational modification of EZH2 but also reveals a unique epigenetic role of OGT in regulating histone methylation. 24474760 12 57 theme functional 1663:1672 arg1 modification 1692:1703 a functional posttranslational modification 1661:1703 a functional posttranslational modification of EZH2 1661:1711 The study not only uncovers a functional posttranslational modification of EZH2 but also reveals a unique epigenetic role of OGT in regulating histone methylation. 24474760 1 58 theme side 209:212 arg1 chain 214:218 side chain 209:218 side chain hydroxyl group 209:233 O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) is the only known enzyme that catalyzes the O-GlcNAcylation of proteins at the Ser or Thr side chain hydroxyl group. 24474760 10 59 theme potential 1417:1425 arg1 genes 1444:1448 potential tumor suppressor genes 1417:1448 potential tumor suppressor genes subject to repression via the OGT-EZH2 axis 1417:1492 Finally, microarray and ChIP analysis have characterized a specific subset of potential tumor suppressor genes subject to repression via the OGT-EZH2 axis. 24474760 7 60 dep demethylases 1002:1013 arg1 demethylases 1002:1013 H3K27 demethylases UTX and JMJD3 996:1027 H3K27 demethylases UTX and JMJD3 996:1027 OGT knockdown specifically down-regulated the protein stability of EZH2, without altering the levels of H3K27 demethylases UTX and JMJD3, and disrupted the integrity of the PRC2 complex. 24474760 7 60 dep demethylases 1002:1013 arg1 JMJD3 1023:1027 JMJD3 1023:1027 JMJD3 1023:1027 OGT knockdown specifically down-regulated the protein stability of EZH2, without altering the levels of H3K27 demethylases UTX and JMJD3, and disrupted the integrity of the PRC2 complex. 24474760 7 60 dep demethylases 1002:1013 arg1 UTX 1015:1017 UTX 1015:1017 UTX 1015:1017 OGT knockdown specifically down-regulated the protein stability of EZH2, without altering the levels of H3K27 demethylases UTX and JMJD3, and disrupted the integrity of the PRC2 complex. 24474760 12 61 theme unique 1732:1737 arg1 role 1750:1753 a unique epigenetic role 1730:1753 a unique epigenetic role of OGT in regulating histone methylation 1730:1794 The study not only uncovers a functional posttranslational modification of EZH2 but also reveals a unique epigenetic role of OGT in regulating histone methylation. 24474760 1 62 theme known 131:135 arg1 enzyme 137:142 the only known enzyme 122:142 the only known enzyme that catalyzes the O-GlcNAcylation of proteins at the Ser or Thr side chain hydroxyl group 122:233 O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) is the only known enzyme that catalyzes the O-GlcNAcylation of proteins at the Ser or Thr side chain hydroxyl group. 24474760 1 62 theme known 131:135 arg1 transferase 101:111 O-linked N-acetylglucosamine (GlcNAc) transferase 63:111 O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) 63:117 O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) is the only known enzyme that catalyzes the O-GlcNAcylation of proteins at the Ser or Thr side chain hydroxyl group. 24474760 1 63 theme chain 214:218 arg1 group 229:233 side chain hydroxyl group 209:233 side chain hydroxyl group 209:233 O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) is the only known enzyme that catalyzes the O-GlcNAcylation of proteins at the Ser or Thr side chain hydroxyl group. 24474760 6 64 theme products 842:849 arg1 level 794:798 the level 790:798 the level of H3K27me3, but not other H3 methylation products, 790:850 We found that the level of H3K27me3, but not other H3 methylation products, was greatly reduced upon OGT depletion. 24474760 1 65 theme hydroxyl 220:227 arg1 group 229:233 side chain hydroxyl group 209:233 side chain hydroxyl group 209:233 O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) is the only known enzyme that catalyzes the O-GlcNAcylation of proteins at the Ser or Thr side chain hydroxyl group. 24474760 7 66 theme OGT 892:894 arg1 knockdown 896:904 OGT knockdown 892:904 OGT knockdown 892:904 OGT knockdown specifically down-regulated the protein stability of EZH2, without altering the levels of H3K27 demethylases UTX and JMJD3, and disrupted the integrity of the PRC2 complex. 24474760 12 67 theme posttranslational 1674:1690 arg1 modification 1692:1703 a functional posttranslational modification 1661:1703 a functional posttranslational modification of EZH2 1661:1711 The study not only uncovers a functional posttranslational modification of EZH2 but also reveals a unique epigenetic role of OGT in regulating histone methylation. 24474760 4 68 theme histone 560:566 arg1 enhancer 586:593 the histone methyltransferase enhancer 556:593 the histone methyltransferase enhancer of zeste homolog 2 (EZH2) in the polycomb repressive complex 2 (PRC2) 556:663 Here we show that OGT is required for the trimethylation of histone 3 at K27 to form the product H3K27me3, a process catalyzed by the histone methyltransferase enhancer of zeste homolog 2 (EZH2) in the polycomb repressive complex 2 (PRC2). 28837623 9 0 theme candidate 1411:1419 arg1 genes 1421:1425 novel candidate genes 1405:1425 novel candidate genes regulating macrophage polarization in humans 1405:1470 Our approach offers a possible avenue to utilize comprehensive genetic tools to identify novel candidate genes regulating macrophage polarization in humans. 28837623 8 1 theme Validation 1121:1130 arg1 experiments 1132:1142 Validation experiments 1121:1142 Validation experiments 1121:1142 Validation experiments confirmed the primary screening results and identified OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) as a novel mediator of M2 polarization in human macrophages. 28837623 8 2 link O-linked 1204:1211 arg1 N-acetylglucosamine 1213:1231 O-linked N-acetylglucosamine 1204:1231 O-linked N-acetylglucosamine (GlcNAc) transferase 1204:1252 Validation experiments confirmed the primary screening results and identified OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) as a novel mediator of M2 polarization in human macrophages. 28837623 8 2 link O-linked 1204:1211 arg1 GlcNAc 1234:1239 GlcNAc 1234:1239 GlcNAc 1234:1239 Validation experiments confirmed the primary screening results and identified OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) as a novel mediator of M2 polarization in human macrophages. 28837623 1 3 theme innate 155:160 arg1 system 169:174 the innate immune system 151:174 the innate immune system regulating host defense, inflammation, tissue homeostasis and cancer 151:243 Macrophages are key cell types of the innate immune system regulating host defense, inflammation, tissue homeostasis and cancer. 28837623 5 4 theme screening 730:738 arg1 loss 713:716 Systematic loss 702:716 Systematic loss of function screening in human primary macrophages 702:767 Systematic loss of function screening in human primary macrophages is limited due to lack of robust gene delivery methods and limited sample availability. 28837623 6 5 theme genetic 954:960 arg1 screens 962:968 genetic screens 954:968 genetic screens 954:968 To overcome these hurdles we developed cell-autonomous assays using the THP-1 cell line allowing genetic screens for human macrophage phenotypes. 28837623 1 6 theme immune 162:167 arg1 system 169:174 the innate immune system 151:174 the innate immune system regulating host defense, inflammation, tissue homeostasis and cancer 151:243 Macrophages are key cell types of the innate immune system regulating host defense, inflammation, tissue homeostasis and cancer. 28837623 8 7 theme M2 1278:1279 arg1 polarization 1281:1292 M2 polarization 1278:1292 M2 polarization 1278:1292 Validation experiments confirmed the primary screening results and identified OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) as a novel mediator of M2 polarization in human macrophages. 28837623 0 8 theme polarization 103:114 arg1 modulators 78:87 candidate modulators 68:87 candidate modulators of macrophage polarization 68:114 Multidimensional pooled shRNA screens in human THP-1 cells identify candidate modulators of macrophage polarization. 28837623 6 9 theme cell 935:938 arg1 line 940:943 the THP-1 cell line 925:943 the THP-1 cell line allowing genetic screens for human macrophage phenotypes 925:1000 To overcome these hurdles we developed cell-autonomous assays using the THP-1 cell line allowing genetic screens for human macrophage phenotypes. 28837623 2 10 theme opposing 296:303 arg1 phenotypes 305:314 diverse and often opposing phenotypes 278:314 diverse and often opposing phenotypes 278:314 Within this functional spectrum diverse and often opposing phenotypes are displayed which are dictated by environmental clues and depend on highly plastic transcriptional programs. 28837623 8 11 theme N-acetylglucosamine 1213:1231 arg1 OGT 1199:1201 OGT 1199:1201 OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) 1199:1253 Validation experiments confirmed the primary screening results and identified OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) as a novel mediator of M2 polarization in human macrophages. 28837623 8 11 theme N-acetylglucosamine 1213:1231 arg1 transferase 1242:1252 O-linked N-acetylglucosamine (GlcNAc) transferase 1204:1252 O-linked N-acetylglucosamine (GlcNAc) transferase 1204:1252 Validation experiments confirmed the primary screening results and identified OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) as a novel mediator of M2 polarization in human macrophages. 28837623 0 12 theme macrophage 92:101 arg1 polarization 103:114 macrophage polarization 92:114 macrophage polarization 92:114 Multidimensional pooled shRNA screens in human THP-1 cells identify candidate modulators of macrophage polarization. 28837623 6 13 theme THP-1 929:933 arg1 line 940:943 the THP-1 cell line 925:943 the THP-1 cell line allowing genetic screens for human macrophage phenotypes 925:1000 To overcome these hurdles we developed cell-autonomous assays using the THP-1 cell line allowing genetic screens for human macrophage phenotypes. 28837623 8 14 from mediator 1266:1273 arg1 macrophages 1303:1313 human macrophages 1297:1313 human macrophages 1297:1313 Validation experiments confirmed the primary screening results and identified OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) as a novel mediator of M2 polarization in human macrophages. 28837623 9 15 theme possible 1338:1345 arg1 avenue 1347:1352 a possible avenue 1336:1352 a possible avenue to utilize comprehensive genetic tools to identify novel candidate genes regulating macrophage polarization in humans 1336:1470 Our approach offers a possible avenue to utilize comprehensive genetic tools to identify novel candidate genes regulating macrophage polarization in humans. 28837623 2 16 theme plastic 393:399 arg1 programs 417:424 highly plastic transcriptional programs 386:424 highly plastic transcriptional programs 386:424 Within this functional spectrum diverse and often opposing phenotypes are displayed which are dictated by environmental clues and depend on highly plastic transcriptional programs. 28837623 1 17 theme system 169:174 arg1 types 142:146 key cell types 133:146 key cell types of the innate immune system regulating host defense, inflammation, tissue homeostasis and cancer 133:243 Macrophages are key cell types of the innate immune system regulating host defense, inflammation, tissue homeostasis and cancer. 28837623 1 17 theme system 169:174 arg1 Macrophages 117:127 Macrophages 117:127 Macrophages 117:127 Macrophages are key cell types of the innate immune system regulating host defense, inflammation, tissue homeostasis and cancer. 28837623 5 18 theme methods 816:822 arg1 lack 787:790 lack 787:790 lack of robust gene delivery methods 787:822 Systematic loss of function screening in human primary macrophages is limited due to lack of robust gene delivery methods and limited sample availability. 28837623 5 18 theme methods 816:822 arg1 availability 843:854 limited sample availability 828:854 limited sample availability 828:854 Systematic loss of function screening in human primary macrophages is limited due to lack of robust gene delivery methods and limited sample availability. 28837623 9 19 theme comprehensive 1365:1377 arg1 tools 1387:1391 comprehensive genetic tools 1365:1391 comprehensive genetic tools 1365:1391 Our approach offers a possible avenue to utilize comprehensive genetic tools to identify novel candidate genes regulating macrophage polarization in humans. 28837623 5 20 theme robust 795:800 arg1 methods 816:822 robust gene delivery methods 795:822 robust gene delivery methods 795:822 Systematic loss of function screening in human primary macrophages is limited due to lack of robust gene delivery methods and limited sample availability. 28837623 2 21 theme diverse 278:284 arg1 phenotypes 305:314 diverse and often opposing phenotypes 278:314 diverse and often opposing phenotypes 278:314 Within this functional spectrum diverse and often opposing phenotypes are displayed which are dictated by environmental clues and depend on highly plastic transcriptional programs. 28837623 2 22 theme transcriptional 401:415 arg1 programs 417:424 highly plastic transcriptional programs 386:424 highly plastic transcriptional programs 386:424 Within this functional spectrum diverse and often opposing phenotypes are displayed which are dictated by environmental clues and depend on highly plastic transcriptional programs. 28837623 0 23 theme pooled 17:22 arg1 screens 30:36 Multidimensional pooled shRNA screens 0:36 Multidimensional pooled shRNA screens in human THP-1 cells 0:57 Multidimensional pooled shRNA screens in human THP-1 cells identify candidate modulators of macrophage polarization. 28837623 9 24 theme novel 1405:1409 arg1 genes 1421:1425 novel candidate genes 1405:1425 novel candidate genes regulating macrophage polarization in humans 1405:1470 Our approach offers a possible avenue to utilize comprehensive genetic tools to identify novel candidate genes regulating macrophage polarization in humans. 28837623 9 25 from polarization 1449:1460 arg1 humans 1465:1470 humans 1465:1470 humans 1465:1470 Our approach offers a possible avenue to utilize comprehensive genetic tools to identify novel candidate genes regulating macrophage polarization in humans. 28837623 7 26 theme M1 1086:1087 arg1 modulators 1109:1118 M1 and M2 polarization modulators 1086:1118 M1 and M2 polarization modulators 1086:1118 We screened 648 chromatin and signaling regulators with a pooled shRNA library for M1 and M2 polarization modulators. 28837623 1 27 theme host 187:190 arg1 defense 192:198 host defense 187:198 host defense 187:198 Macrophages are key cell types of the innate immune system regulating host defense, inflammation, tissue homeostasis and cancer. 28837623 0 28 theme Multidimensional 0:15 arg1 screens 30:36 Multidimensional pooled shRNA screens 0:36 Multidimensional pooled shRNA screens in human THP-1 cells 0:57 Multidimensional pooled shRNA screens in human THP-1 cells identify candidate modulators of macrophage polarization. 28837623 8 29 theme polarization 1281:1292 arg1 OGT 1199:1201 OGT 1199:1201 OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) 1199:1253 Validation experiments confirmed the primary screening results and identified OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) as a novel mediator of M2 polarization in human macrophages. 28837623 8 29 theme polarization 1281:1292 arg1 mediator 1266:1273 a novel mediator 1258:1273 a novel mediator of M2 polarization in human macrophages 1258:1313 Validation experiments confirmed the primary screening results and identified OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) as a novel mediator of M2 polarization in human macrophages. 28837623 7 30 theme M2 1093:1094 arg1 modulators 1109:1118 M1 and M2 polarization modulators 1086:1118 M1 and M2 polarization modulators 1086:1118 We screened 648 chromatin and signaling regulators with a pooled shRNA library for M1 and M2 polarization modulators. 28837623 7 31 theme polarization 1096:1107 arg1 modulators 1109:1118 M1 and M2 polarization modulators 1086:1118 M1 and M2 polarization modulators 1086:1118 We screened 648 chromatin and signaling regulators with a pooled shRNA library for M1 and M2 polarization modulators. 28837623 3 32 theme classical 444:452 arg1 phenotypes 507:516 the 'classical' (M1) and 'alternative' (M2) macrophage polarization phenotypes 439:516 the 'classical' (M1) and 'alternative' (M2) macrophage polarization phenotypes 439:516 Among these the 'classical' (M1) and 'alternative' (M2) macrophage polarization phenotypes are the best characterized. 28837623 4 33 theme novel 605:609 arg1 possibilities 636:648 novel therapeutic intervention possibilities 605:648 novel therapeutic intervention possibilities for chronic inflammation, wound healing and cancer 605:699 Understanding macrophage polarization in humans may reveal novel therapeutic intervention possibilities for chronic inflammation, wound healing and cancer. 28837623 5 34 theme limited 828:834 arg1 availability 843:854 limited sample availability 828:854 limited sample availability 828:854 Systematic loss of function screening in human primary macrophages is limited due to lack of robust gene delivery methods and limited sample availability. 28837623 5 35 theme function 721:728 arg1 screening 730:738 function screening 721:738 function screening 721:738 Systematic loss of function screening in human primary macrophages is limited due to lack of robust gene delivery methods and limited sample availability. 28837623 8 36 theme novel 1260:1264 arg1 OGT 1199:1201 OGT 1199:1201 OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) 1199:1253 Validation experiments confirmed the primary screening results and identified OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) as a novel mediator of M2 polarization in human macrophages. 28837623 8 36 theme novel 1260:1264 arg1 mediator 1266:1273 a novel mediator 1258:1273 a novel mediator of M2 polarization in human macrophages 1258:1313 Validation experiments confirmed the primary screening results and identified OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) as a novel mediator of M2 polarization in human macrophages. 28837623 9 37 theme macrophage 1438:1447 arg1 polarization 1449:1460 macrophage polarization 1438:1460 macrophage polarization in humans 1438:1470 Our approach offers a possible avenue to utilize comprehensive genetic tools to identify novel candidate genes regulating macrophage polarization in humans. 28837623 4 38 theme chronic 654:660 arg1 inflammation 662:673 chronic inflammation 654:673 chronic inflammation 654:673 Understanding macrophage polarization in humans may reveal novel therapeutic intervention possibilities for chronic inflammation, wound healing and cancer. 28837623 0 39 theme shRNA 24:28 arg1 screens 30:36 Multidimensional pooled shRNA screens 0:36 Multidimensional pooled shRNA screens in human THP-1 cells 0:57 Multidimensional pooled shRNA screens in human THP-1 cells identify candidate modulators of macrophage polarization. 28837623 3 40 dep best 526:529 arg1 are 518:520 are 518:520 are the best characterized 518:543 Among these the 'classical' (M1) and 'alternative' (M2) macrophage polarization phenotypes are the best characterized. 28837623 6 41 theme cell-autonomous 896:910 arg1 assays 912:917 cell-autonomous assays 896:917 cell-autonomous assays using the THP-1 cell line allowing genetic screens for human macrophage phenotypes 896:1000 To overcome these hurdles we developed cell-autonomous assays using the THP-1 cell line allowing genetic screens for human macrophage phenotypes. 28837623 3 42 theme macrophage 483:492 arg1 phenotypes 507:516 the 'classical' (M1) and 'alternative' (M2) macrophage polarization phenotypes 439:516 the 'classical' (M1) and 'alternative' (M2) macrophage polarization phenotypes 439:516 Among these the 'classical' (M1) and 'alternative' (M2) macrophage polarization phenotypes are the best characterized. 28837623 5 43 theme sample 836:841 arg1 availability 843:854 limited sample availability 828:854 limited sample availability 828:854 Systematic loss of function screening in human primary macrophages is limited due to lack of robust gene delivery methods and limited sample availability. 28837623 0 44 theme human 41:45 arg1 cells 53:57 human THP-1 cells 41:57 human THP-1 cells 41:57 Multidimensional pooled shRNA screens in human THP-1 cells identify candidate modulators of macrophage polarization. 28837623 4 45 theme macrophage 560:569 arg1 polarization 571:582 macrophage polarization 560:582 macrophage polarization in humans 560:592 Understanding macrophage polarization in humans may reveal novel therapeutic intervention possibilities for chronic inflammation, wound healing and cancer. 28837623 5 46 theme gene 802:805 arg1 methods 816:822 robust gene delivery methods 795:822 robust gene delivery methods 795:822 Systematic loss of function screening in human primary macrophages is limited due to lack of robust gene delivery methods and limited sample availability. 28837623 6 47 theme macrophage 980:989 arg1 phenotypes 991:1000 human macrophage phenotypes 974:1000 human macrophage phenotypes 974:1000 To overcome these hurdles we developed cell-autonomous assays using the THP-1 cell line allowing genetic screens for human macrophage phenotypes. 28837623 5 48 theme human 743:747 arg1 macrophages 757:767 human primary macrophages 743:767 human primary macrophages 743:767 Systematic loss of function screening in human primary macrophages is limited due to lack of robust gene delivery methods and limited sample availability. 28837623 3 49 dep classical 444:452 arg1 M2 479:480 M2 479:480 M2 479:480 Among these the 'classical' (M1) and 'alternative' (M2) macrophage polarization phenotypes are the best characterized. 28837623 3 49 dep classical 444:452 arg1 M1 456:457 M1 456:457 M1 456:457 Among these the 'classical' (M1) and 'alternative' (M2) macrophage polarization phenotypes are the best characterized. 28837623 1 50 theme tissue 215:220 arg1 homeostasis 222:232 tissue homeostasis 215:232 tissue homeostasis 215:232 Macrophages are key cell types of the innate immune system regulating host defense, inflammation, tissue homeostasis and cancer. 28837623 5 51 theme delivery 807:814 arg1 methods 816:822 robust gene delivery methods 795:822 robust gene delivery methods 795:822 Systematic loss of function screening in human primary macrophages is limited due to lack of robust gene delivery methods and limited sample availability. 28837623 5 52 theme primary 749:755 arg1 macrophages 757:767 human primary macrophages 743:767 human primary macrophages 743:767 Systematic loss of function screening in human primary macrophages is limited due to lack of robust gene delivery methods and limited sample availability. 28837623 8 53 theme primary 1158:1164 arg1 results 1176:1182 the primary screening results 1154:1182 the primary screening results 1154:1182 Validation experiments confirmed the primary screening results and identified OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) as a novel mediator of M2 polarization in human macrophages. 28837623 7 54 theme pooled 1061:1066 arg1 library 1074:1080 a pooled shRNA library 1059:1080 a pooled shRNA library for M1 and M2 polarization modulators 1059:1118 We screened 648 chromatin and signaling regulators with a pooled shRNA library for M1 and M2 polarization modulators. 28837623 2 55 theme environmental 352:364 arg1 clues 366:370 environmental clues 352:370 environmental clues 352:370 Within this functional spectrum diverse and often opposing phenotypes are displayed which are dictated by environmental clues and depend on highly plastic transcriptional programs. 28837623 0 56 theme THP-1 47:51 arg1 cells 53:57 human THP-1 cells 41:57 human THP-1 cells 41:57 Multidimensional pooled shRNA screens in human THP-1 cells identify candidate modulators of macrophage polarization. 28837623 5 57 theme Systematic 702:711 arg1 loss 713:716 Systematic loss 702:716 Systematic loss of function screening in human primary macrophages 702:767 Systematic loss of function screening in human primary macrophages is limited due to lack of robust gene delivery methods and limited sample availability. 28837623 1 58 theme key 133:135 arg1 types 142:146 key cell types 133:146 key cell types of the innate immune system regulating host defense, inflammation, tissue homeostasis and cancer 133:243 Macrophages are key cell types of the innate immune system regulating host defense, inflammation, tissue homeostasis and cancer. 28837623 1 58 theme key 133:135 arg1 Macrophages 117:127 Macrophages 117:127 Macrophages 117:127 Macrophages are key cell types of the innate immune system regulating host defense, inflammation, tissue homeostasis and cancer. 28837623 6 59 dep developed 886:894 arg1 overcome 860:867 overcome 860:867 To overcome these hurdles 857:881 To overcome these hurdles we developed cell-autonomous assays using the THP-1 cell line allowing genetic screens for human macrophage phenotypes. 28837623 7 60 theme shRNA 1068:1072 arg1 library 1074:1080 a pooled shRNA library 1059:1080 a pooled shRNA library for M1 and M2 polarization modulators 1059:1118 We screened 648 chromatin and signaling regulators with a pooled shRNA library for M1 and M2 polarization modulators. 28837623 8 61 theme O-linked 1204:1211 arg1 N-acetylglucosamine 1213:1231 O-linked N-acetylglucosamine 1204:1231 O-linked N-acetylglucosamine (GlcNAc) transferase 1204:1252 Validation experiments confirmed the primary screening results and identified OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) as a novel mediator of M2 polarization in human macrophages. 28837623 8 61 theme O-linked 1204:1211 arg1 GlcNAc 1234:1239 GlcNAc 1234:1239 GlcNAc 1234:1239 Validation experiments confirmed the primary screening results and identified OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) as a novel mediator of M2 polarization in human macrophages. 28837623 8 62 theme human 1297:1301 arg1 macrophages 1303:1313 human macrophages 1297:1313 human macrophages 1297:1313 Validation experiments confirmed the primary screening results and identified OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) as a novel mediator of M2 polarization in human macrophages. 28837623 1 63 theme cell 137:140 arg1 types 142:146 key cell types 133:146 key cell types of the innate immune system regulating host defense, inflammation, tissue homeostasis and cancer 133:243 Macrophages are key cell types of the innate immune system regulating host defense, inflammation, tissue homeostasis and cancer. 28837623 1 63 theme cell 137:140 arg1 Macrophages 117:127 Macrophages 117:127 Macrophages 117:127 Macrophages are key cell types of the innate immune system regulating host defense, inflammation, tissue homeostasis and cancer. 28837623 5 64 from loss 713:716 arg1 macrophages 757:767 human primary macrophages 743:767 human primary macrophages 743:767 Systematic loss of function screening in human primary macrophages is limited due to lack of robust gene delivery methods and limited sample availability. 28837623 4 65 theme therapeutic 611:621 arg1 possibilities 636:648 novel therapeutic intervention possibilities 605:648 novel therapeutic intervention possibilities for chronic inflammation, wound healing and cancer 605:699 Understanding macrophage polarization in humans may reveal novel therapeutic intervention possibilities for chronic inflammation, wound healing and cancer. 28837623 8 66 theme screening 1166:1174 arg1 results 1176:1182 the primary screening results 1154:1182 the primary screening results 1154:1182 Validation experiments confirmed the primary screening results and identified OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) as a novel mediator of M2 polarization in human macrophages. 28837623 2 67 theme functional 258:267 arg1 spectrum 269:276 this functional spectrum 253:276 this functional spectrum 253:276 Within this functional spectrum diverse and often opposing phenotypes are displayed which are dictated by environmental clues and depend on highly plastic transcriptional programs. 28837623 3 68 theme alternative 465:475 arg1 phenotypes 507:516 the 'classical' (M1) and 'alternative' (M2) macrophage polarization phenotypes 439:516 the 'classical' (M1) and 'alternative' (M2) macrophage polarization phenotypes 439:516 Among these the 'classical' (M1) and 'alternative' (M2) macrophage polarization phenotypes are the best characterized. 28837623 0 69 theme candidate 68:76 arg1 modulators 78:87 candidate modulators 68:87 candidate modulators of macrophage polarization 68:114 Multidimensional pooled shRNA screens in human THP-1 cells identify candidate modulators of macrophage polarization. 28837623 9 70 theme genetic 1379:1385 arg1 tools 1387:1391 comprehensive genetic tools 1365:1391 comprehensive genetic tools 1365:1391 Our approach offers a possible avenue to utilize comprehensive genetic tools to identify novel candidate genes regulating macrophage polarization in humans. 28837623 7 71 theme signaling 1033:1041 arg1 regulators 1043:1052 648 chromatin and signaling regulators 1015:1052 regulators 1043:1052 We screened 648 chromatin and signaling regulators with a pooled shRNA library for M1 and M2 polarization modulators. 28837623 3 72 theme polarization 494:505 arg1 phenotypes 507:516 the 'classical' (M1) and 'alternative' (M2) macrophage polarization phenotypes 439:516 the 'classical' (M1) and 'alternative' (M2) macrophage polarization phenotypes 439:516 Among these the 'classical' (M1) and 'alternative' (M2) macrophage polarization phenotypes are the best characterized. 28837623 4 73 theme wound 676:680 arg1 healing 682:688 wound healing 676:688 wound healing 676:688 Understanding macrophage polarization in humans may reveal novel therapeutic intervention possibilities for chronic inflammation, wound healing and cancer. 28837623 0 74 from screens 30:36 arg1 cells 53:57 human THP-1 cells 41:57 human THP-1 cells 41:57 Multidimensional pooled shRNA screens in human THP-1 cells identify candidate modulators of macrophage polarization. 28837623 7 75 theme 648 1015:1017 arg1 chromatin 1019:1027 648 chromatin and signaling regulators 1015:1052 chromatin 1019:1027 We screened 648 chromatin and signaling regulators with a pooled shRNA library for M1 and M2 polarization modulators. 28837623 4 76 from polarization 571:582 arg1 humans 587:592 humans 587:592 humans 587:592 Understanding macrophage polarization in humans may reveal novel therapeutic intervention possibilities for chronic inflammation, wound healing and cancer. 28837623 6 77 theme human 974:978 arg1 phenotypes 991:1000 human macrophage phenotypes 974:1000 human macrophage phenotypes 974:1000 To overcome these hurdles we developed cell-autonomous assays using the THP-1 cell line allowing genetic screens for human macrophage phenotypes. 28837623 4 78 theme intervention 623:634 arg1 possibilities 636:648 novel therapeutic intervention possibilities 605:648 novel therapeutic intervention possibilities for chronic inflammation, wound healing and cancer 605:699 Understanding macrophage polarization in humans may reveal novel therapeutic intervention possibilities for chronic inflammation, wound healing and cancer. 28427939 8 0 theme β-catenin/Arm 1083:1095 arg1 modification 1067:1078 the modification 1063:1078 the modification of β-catenin/Arm with O-linked beta-N-acetylglucosamine (O-GlcNAc), and failure of the association between β-catenin/Arm and pygopus(pygo) protein, which is required for transcriptional activation of Wnt target genes 1063:1295 Further studies reveal that NRAGE leads to the modification of β-catenin/Arm with O-linked beta-N-acetylglucosamine (O-GlcNAc), and failure of the association between β-catenin/Arm and pygopus(pygo) protein, which is required for transcriptional activation of Wnt target genes. 28427939 3 1 dep signals 354:360 arg1 response 338:345 response 338:345 response 338:345 It is generally accepted that in response to Wnt signals, β-catenin accumulates in the cytoplasm and is imported into the nucleus where it recruits LEF/TCF transcription factors to activate the expression of target genes. 28427939 7 2 theme β-catenin 971:979 arg1 localization 955:966 nuclear localization 947:966 nuclear localization of β-catenin 947:979 To our surprise, NRAGE induces nuclear localization of β-catenin and increases its DNA binding ability. 28427939 1 3 theme tumor 146:150 arg1 formation 152:160 tumor formation 146:160 tumor formation 146:160 The Wnt pathway is crucial for animal development, as well as tumor formation. 28427939 5 4 theme function 736:743 arg1 loss 728:731 loss 728:731 loss of function of NRAGE by RNA interference (RNAi) 728:779 Consistent with this finding, loss of function of NRAGE by RNA interference (RNAi) activates the Wnt pathway. 28427939 8 5 theme O-linked 1102:1109 arg1 O-GlcNAc 1137:1144 O-GlcNAc 1137:1144 O-GlcNAc 1137:1144 Further studies reveal that NRAGE leads to the modification of β-catenin/Arm with O-linked beta-N-acetylglucosamine (O-GlcNAc), and failure of the association between β-catenin/Arm and pygopus(pygo) protein, which is required for transcriptional activation of Wnt target genes. 28427939 8 5 theme O-linked 1102:1109 arg1 beta-N-acetylglucosamine 1111:1134 O-linked beta-N-acetylglucosamine 1102:1134 O-linked beta-N-acetylglucosamine (O-GlcNAc) 1102:1145 Further studies reveal that NRAGE leads to the modification of β-catenin/Arm with O-linked beta-N-acetylglucosamine (O-GlcNAc), and failure of the association between β-catenin/Arm and pygopus(pygo) protein, which is required for transcriptional activation of Wnt target genes. 28427939 2 6 theme differentiation 270:284 arg1 mechanism 236:244 the mechanism 232:244 the mechanism of the cell cycle, cell differentiation and tumorigenesis 232:302 Understanding the regulation of Wnt signaling will help to elucidate the mechanism of the cell cycle, cell differentiation and tumorigenesis. 28427939 9 7 theme Wnt 1363:1365 arg1 signaling 1367:1375 Wnt signaling 1363:1375 Wnt signaling 1363:1375 Therefore, our findings suggest a novel mechanism for regulating Wnt signaling. 28427939 3 8 theme Wnt 350:352 arg1 signals 354:360 Wnt signals 350:360 Wnt signals 350:360 It is generally accepted that in response to Wnt signals, β-catenin accumulates in the cytoplasm and is imported into the nucleus where it recruits LEF/TCF transcription factors to activate the expression of target genes. 28427939 8 9 theme Wnt 1280:1282 arg1 genes 1291:1295 Wnt target genes 1280:1295 Wnt target genes 1280:1295 Further studies reveal that NRAGE leads to the modification of β-catenin/Arm with O-linked beta-N-acetylglucosamine (O-GlcNAc), and failure of the association between β-catenin/Arm and pygopus(pygo) protein, which is required for transcriptional activation of Wnt target genes. 28427939 8 10 with modification 1067:1078 arg1 O-GlcNAc 1137:1144 O-GlcNAc 1137:1144 O-GlcNAc 1137:1144 Further studies reveal that NRAGE leads to the modification of β-catenin/Arm with O-linked beta-N-acetylglucosamine (O-GlcNAc), and failure of the association between β-catenin/Arm and pygopus(pygo) protein, which is required for transcriptional activation of Wnt target genes. 28427939 8 10 with modification 1067:1078 arg1 beta-N-acetylglucosamine 1111:1134 O-linked beta-N-acetylglucosamine 1102:1134 O-linked beta-N-acetylglucosamine (O-GlcNAc) 1102:1145 Further studies reveal that NRAGE leads to the modification of β-catenin/Arm with O-linked beta-N-acetylglucosamine (O-GlcNAc), and failure of the association between β-catenin/Arm and pygopus(pygo) protein, which is required for transcriptional activation of Wnt target genes. 28427939 8 10 with modification 1067:1078 arg1 failure 1152:1158 failure 1152:1158 failure of the association between β-catenin/Arm and pygopus(pygo) protein, which is required for transcriptional activation of Wnt target genes 1152:1295 Further studies reveal that NRAGE leads to the modification of β-catenin/Arm with O-linked beta-N-acetylglucosamine (O-GlcNAc), and failure of the association between β-catenin/Arm and pygopus(pygo) protein, which is required for transcriptional activation of Wnt target genes. 28427939 2 11 theme cell 265:268 arg1 differentiation 270:284 cell differentiation 265:284 cell differentiation 265:284 Understanding the regulation of Wnt signaling will help to elucidate the mechanism of the cell cycle, cell differentiation and tumorigenesis. 28427939 4 12 theme human 557:561 arg1 protein 615:621 a neurotrophin receptor p75 (p75NTR) binding protein 570:621 a neurotrophin receptor p75 (p75NTR) binding protein 570:621 In this study, we report that human NRAGE, a neurotrophin receptor p75 (p75NTR) binding protein, markedly suppresses the expression of genes activated by the Wnt pathway. 28427939 4 12 theme human 557:561 arg1 NRAGE 563:567 human NRAGE 557:567 human NRAGE 557:567 In this study, we report that human NRAGE, a neurotrophin receptor p75 (p75NTR) binding protein, markedly suppresses the expression of genes activated by the Wnt pathway. 28427939 9 13 theme novel 1332:1336 arg1 mechanism 1338:1346 a novel mechanism 1330:1346 a novel mechanism for regulating Wnt signaling 1330:1375 Therefore, our findings suggest a novel mechanism for regulating Wnt signaling. 28427939 3 14 theme target 513:518 arg1 genes 520:524 target genes 513:524 target genes 513:524 It is generally accepted that in response to Wnt signals, β-catenin accumulates in the cytoplasm and is imported into the nucleus where it recruits LEF/TCF transcription factors to activate the expression of target genes. 28427939 8 15 theme genes 1291:1295 arg1 activation 1266:1275 transcriptional activation 1250:1275 transcriptional activation of Wnt target genes 1250:1295 Further studies reveal that NRAGE leads to the modification of β-catenin/Arm with O-linked beta-N-acetylglucosamine (O-GlcNAc), and failure of the association between β-catenin/Arm and pygopus(pygo) protein, which is required for transcriptional activation of Wnt target genes. 28427939 1 16 theme Wnt 88:90 arg1 crucial 103:109 crucial 103:109 crucial 103:109 The Wnt pathway is crucial for animal development, as well as tumor formation. 28427939 1 16 theme Wnt 88:90 arg1 pathway 92:98 The Wnt pathway 84:98 The Wnt pathway 84:98 The Wnt pathway is crucial for animal development, as well as tumor formation. 28427939 4 17 theme binding 607:613 arg1 protein 615:621 a neurotrophin receptor p75 (p75NTR) binding protein 570:621 a neurotrophin receptor p75 (p75NTR) binding protein 570:621 In this study, we report that human NRAGE, a neurotrophin receptor p75 (p75NTR) binding protein, markedly suppresses the expression of genes activated by the Wnt pathway. 28427939 4 17 theme binding 607:613 arg1 NRAGE 563:567 human NRAGE 557:567 human NRAGE 557:567 In this study, we report that human NRAGE, a neurotrophin receptor p75 (p75NTR) binding protein, markedly suppresses the expression of genes activated by the Wnt pathway. 28427939 5 18 theme NRAGE 748:752 arg1 function 736:743 function 736:743 function of NRAGE 736:752 Consistent with this finding, loss of function of NRAGE by RNA interference (RNAi) activates the Wnt pathway. 28427939 4 19 theme Wnt 685:687 arg1 pathway 689:695 the Wnt pathway 681:695 the Wnt pathway 681:695 In this study, we report that human NRAGE, a neurotrophin receptor p75 (p75NTR) binding protein, markedly suppresses the expression of genes activated by the Wnt pathway. 28427939 5 20 theme RNA 757:759 arg1 RNAi 775:778 RNAi 775:778 RNAi 775:778 Consistent with this finding, loss of function of NRAGE by RNA interference (RNAi) activates the Wnt pathway. 28427939 5 20 theme RNA 757:759 arg1 interference 761:772 RNA interference 757:772 RNA interference (RNAi) 757:779 Consistent with this finding, loss of function of NRAGE by RNA interference (RNAi) activates the Wnt pathway. 28427939 7 21 theme binding 1003:1009 arg1 ability 1011:1017 its DNA binding ability 995:1017 its DNA binding ability 995:1017 To our surprise, NRAGE induces nuclear localization of β-catenin and increases its DNA binding ability. 28427939 2 22 theme tumorigenesis 290:302 arg1 mechanism 236:244 the mechanism 232:244 the mechanism of the cell cycle, cell differentiation and tumorigenesis 232:302 Understanding the regulation of Wnt signaling will help to elucidate the mechanism of the cell cycle, cell differentiation and tumorigenesis. 28427939 0 23 theme β-catenin/Arm 14:26 arg1 O-GlcNAcylation 28:42 β-catenin/Arm O-GlcNAcylation 14:42 β-catenin/Arm O-GlcNAcylation 14:42 NRAGE induces β-catenin/Arm O-GlcNAcylation and negatively regulates Wnt signaling. 28427939 6 24 theme Xenopus 899:905 arg1 embryos 907:913 Xenopus embryos 899:913 Xenopus embryos 899:913 Moreover, NRAGE suppresses the induction of axis duplication by microinjected β-catenin in Xenopus embryos. 28427939 4 25 theme p75 594:596 arg1 protein 615:621 a neurotrophin receptor p75 (p75NTR) binding protein 570:621 a neurotrophin receptor p75 (p75NTR) binding protein 570:621 In this study, we report that human NRAGE, a neurotrophin receptor p75 (p75NTR) binding protein, markedly suppresses the expression of genes activated by the Wnt pathway. 28427939 4 25 theme p75 594:596 arg1 NRAGE 563:567 human NRAGE 557:567 human NRAGE 557:567 In this study, we report that human NRAGE, a neurotrophin receptor p75 (p75NTR) binding protein, markedly suppresses the expression of genes activated by the Wnt pathway. 28427939 7 26 theme DNA 999:1001 arg1 ability 1011:1017 its DNA binding ability 995:1017 its DNA binding ability 995:1017 To our surprise, NRAGE induces nuclear localization of β-catenin and increases its DNA binding ability. 28427939 5 27 with Consistent 698:707 arg1 finding 719:725 this finding 714:725 this finding 714:725 Consistent with this finding, loss of function of NRAGE by RNA interference (RNAi) activates the Wnt pathway. 28427939 7 28 theme nuclear 947:953 arg1 localization 955:966 nuclear localization 947:966 nuclear localization of β-catenin 947:979 To our surprise, NRAGE induces nuclear localization of β-catenin and increases its DNA binding ability. 28427939 0 29 theme Wnt 69:71 arg1 signaling 73:81 Wnt signaling 69:81 Wnt signaling 69:81 NRAGE induces β-catenin/Arm O-GlcNAcylation and negatively regulates Wnt signaling. 28427939 6 30 theme microinjected 872:884 arg1 β-catenin 886:894 microinjected β-catenin 872:894 microinjected β-catenin in Xenopus embryos 872:913 Moreover, NRAGE suppresses the induction of axis duplication by microinjected β-catenin in Xenopus embryos. 28427939 1 31 theme animal 115:120 arg1 development 122:132 animal development 115:132 animal development 115:132 The Wnt pathway is crucial for animal development, as well as tumor formation. 28427939 8 32 theme Further 1020:1026 arg1 studies 1028:1034 Further studies 1020:1034 Further studies 1020:1034 Further studies reveal that NRAGE leads to the modification of β-catenin/Arm with O-linked beta-N-acetylglucosamine (O-GlcNAc), and failure of the association between β-catenin/Arm and pygopus(pygo) protein, which is required for transcriptional activation of Wnt target genes. 28427939 4 33 theme genes 662:666 arg1 expression 648:657 the expression 644:657 the expression of genes activated by the Wnt pathway 644:695 In this study, we report that human NRAGE, a neurotrophin receptor p75 (p75NTR) binding protein, markedly suppresses the expression of genes activated by the Wnt pathway. 28427939 6 34 theme duplication 857:867 arg1 induction 839:847 the induction 835:847 the induction of axis duplication by microinjected β-catenin in Xenopus embryos 835:913 Moreover, NRAGE suppresses the induction of axis duplication by microinjected β-catenin in Xenopus embryos. 28427939 6 35 from β-catenin 886:894 arg1 embryos 907:913 Xenopus embryos 899:913 Xenopus embryos 899:913 Moreover, NRAGE suppresses the induction of axis duplication by microinjected β-catenin in Xenopus embryos. 28427939 2 36 theme signaling 199:207 arg1 regulation 181:190 the regulation 177:190 the regulation of Wnt signaling 177:207 Understanding the regulation of Wnt signaling will help to elucidate the mechanism of the cell cycle, cell differentiation and tumorigenesis. 28427939 2 37 theme cell 253:256 arg1 cycle 258:262 cell cycle 253:262 cell cycle 253:262 Understanding the regulation of Wnt signaling will help to elucidate the mechanism of the cell cycle, cell differentiation and tumorigenesis. 28427939 3 38 theme LEF/TCF 453:459 arg1 factors 475:481 LEF/TCF transcription factors 453:481 LEF/TCF transcription factors 453:481 It is generally accepted that in response to Wnt signals, β-catenin accumulates in the cytoplasm and is imported into the nucleus where it recruits LEF/TCF transcription factors to activate the expression of target genes. 28427939 8 39 dep β-catenin/Arm 1187:1199 arg1 protein 1219:1225 protein 1219:1225 protein 1219:1225 Further studies reveal that NRAGE leads to the modification of β-catenin/Arm with O-linked beta-N-acetylglucosamine (O-GlcNAc), and failure of the association between β-catenin/Arm and pygopus(pygo) protein, which is required for transcriptional activation of Wnt target genes. 28427939 3 40 theme genes 520:524 arg1 expression 499:508 the expression 495:508 the expression of target genes 495:524 It is generally accepted that in response to Wnt signals, β-catenin accumulates in the cytoplasm and is imported into the nucleus where it recruits LEF/TCF transcription factors to activate the expression of target genes. 28427939 2 41 theme Wnt 195:197 arg1 signaling 199:207 Wnt signaling 195:207 Wnt signaling 195:207 Understanding the regulation of Wnt signaling will help to elucidate the mechanism of the cell cycle, cell differentiation and tumorigenesis. 28427939 8 42 theme target 1284:1289 arg1 genes 1291:1295 Wnt target genes 1280:1295 Wnt target genes 1280:1295 Further studies reveal that NRAGE leads to the modification of β-catenin/Arm with O-linked beta-N-acetylglucosamine (O-GlcNAc), and failure of the association between β-catenin/Arm and pygopus(pygo) protein, which is required for transcriptional activation of Wnt target genes. 28427939 3 43 theme transcription 461:473 arg1 factors 475:481 LEF/TCF transcription factors 453:481 LEF/TCF transcription factors 453:481 It is generally accepted that in response to Wnt signals, β-catenin accumulates in the cytoplasm and is imported into the nucleus where it recruits LEF/TCF transcription factors to activate the expression of target genes. 28427939 8 44 theme association 1167:1177 arg1 O-GlcNAc 1137:1144 O-GlcNAc 1137:1144 O-GlcNAc 1137:1144 Further studies reveal that NRAGE leads to the modification of β-catenin/Arm with O-linked beta-N-acetylglucosamine (O-GlcNAc), and failure of the association between β-catenin/Arm and pygopus(pygo) protein, which is required for transcriptional activation of Wnt target genes. 28427939 8 44 theme association 1167:1177 arg1 beta-N-acetylglucosamine 1111:1134 O-linked beta-N-acetylglucosamine 1102:1134 O-linked beta-N-acetylglucosamine (O-GlcNAc) 1102:1145 Further studies reveal that NRAGE leads to the modification of β-catenin/Arm with O-linked beta-N-acetylglucosamine (O-GlcNAc), and failure of the association between β-catenin/Arm and pygopus(pygo) protein, which is required for transcriptional activation of Wnt target genes. 28427939 8 44 theme association 1167:1177 arg1 failure 1152:1158 failure 1152:1158 failure of the association between β-catenin/Arm and pygopus(pygo) protein, which is required for transcriptional activation of Wnt target genes 1152:1295 Further studies reveal that NRAGE leads to the modification of β-catenin/Arm with O-linked beta-N-acetylglucosamine (O-GlcNAc), and failure of the association between β-catenin/Arm and pygopus(pygo) protein, which is required for transcriptional activation of Wnt target genes. 28427939 8 45 theme transcriptional 1250:1264 arg1 activation 1266:1275 transcriptional activation 1250:1275 transcriptional activation of Wnt target genes 1250:1295 Further studies reveal that NRAGE leads to the modification of β-catenin/Arm with O-linked beta-N-acetylglucosamine (O-GlcNAc), and failure of the association between β-catenin/Arm and pygopus(pygo) protein, which is required for transcriptional activation of Wnt target genes. 28427939 5 46 theme Wnt 795:797 arg1 pathway 799:805 the Wnt pathway 791:805 the Wnt pathway 791:805 Consistent with this finding, loss of function of NRAGE by RNA interference (RNAi) activates the Wnt pathway. 28427939 4 47 theme receptor 585:592 arg1 p75NTR 599:604 p75NTR 599:604 p75NTR 599:604 In this study, we report that human NRAGE, a neurotrophin receptor p75 (p75NTR) binding protein, markedly suppresses the expression of genes activated by the Wnt pathway. 28427939 4 47 theme receptor 585:592 arg1 p75 594:596 neurotrophin receptor p75 572:596 a neurotrophin receptor p75 (p75NTR) binding protein 570:621 In this study, we report that human NRAGE, a neurotrophin receptor p75 (p75NTR) binding protein, markedly suppresses the expression of genes activated by the Wnt pathway. 28427939 2 48 theme cycle 258:262 arg1 mechanism 236:244 the mechanism 232:244 the mechanism of the cell cycle, cell differentiation and tumorigenesis 232:302 Understanding the regulation of Wnt signaling will help to elucidate the mechanism of the cell cycle, cell differentiation and tumorigenesis. 28427939 6 49 theme axis 852:855 arg1 duplication 857:867 axis duplication 852:867 axis duplication 852:867 Moreover, NRAGE suppresses the induction of axis duplication by microinjected β-catenin in Xenopus embryos. 28427939 8 50 link O-linked 1102:1109 arg1 O-GlcNAc 1137:1144 O-GlcNAc 1137:1144 O-GlcNAc 1137:1144 Further studies reveal that NRAGE leads to the modification of β-catenin/Arm with O-linked beta-N-acetylglucosamine (O-GlcNAc), and failure of the association between β-catenin/Arm and pygopus(pygo) protein, which is required for transcriptional activation of Wnt target genes. 28427939 8 50 link O-linked 1102:1109 arg1 beta-N-acetylglucosamine 1111:1134 O-linked beta-N-acetylglucosamine 1102:1134 O-linked beta-N-acetylglucosamine (O-GlcNAc) 1102:1145 Further studies reveal that NRAGE leads to the modification of β-catenin/Arm with O-linked beta-N-acetylglucosamine (O-GlcNAc), and failure of the association between β-catenin/Arm and pygopus(pygo) protein, which is required for transcriptional activation of Wnt target genes. 28427939 4 51 theme neurotrophin 572:583 arg1 p75NTR 599:604 p75NTR 599:604 p75NTR 599:604 In this study, we report that human NRAGE, a neurotrophin receptor p75 (p75NTR) binding protein, markedly suppresses the expression of genes activated by the Wnt pathway. 28427939 4 51 theme neurotrophin 572:583 arg1 p75 594:596 neurotrophin receptor p75 572:596 a neurotrophin receptor p75 (p75NTR) binding protein 570:621 In this study, we report that human NRAGE, a neurotrophin receptor p75 (p75NTR) binding protein, markedly suppresses the expression of genes activated by the Wnt pathway. 27812179 8 0 theme cadherin 1232:1239 arg1 superfamilies 1252:1264 the cadherin and plexin superfamilies 1228:1264 the cadherin and plexin superfamilies 1228:1264 Among the candidates identified are members of the cadherin and plexin superfamilies and the perineural net protein neurocan. 27812179 6 1 theme inhibitory 987:996 arg1 neurons 1008:1014 inhibitory GABAergic neurons 987:1014 inhibitory GABAergic neurons 987:1014 Using this tool, we observed that mono-O-mannosyl glycans occur ubiquitously throughout the murine brain but are especially enriched at inhibitory GABAergic neurons and at the perineural nets. 27812179 7 2 theme mass 1052:1055 arg1 approach 1076:1083 a mass spectrometry-based approach 1050:1083 a mass spectrometry-based approach 1050:1083 Using a mass spectrometry-based approach, we further identified glycoproteins from the murine brain that bear single O-mannose residues. 27812179 7 3 from brain 1138:1142 arg1 glycoproteins 1108:1120 glycoproteins 1108:1120 glycoproteins from the murine brain that bear single O-mannose residues 1108:1178 Using a mass spectrometry-based approach, we further identified glycoproteins from the murine brain that bear single O-mannose residues. 27812179 0 4 theme Glycans 75:81 arg1 Identification 87:100 Identification 87:100 Identification of New Substrates 87:118 Protein O-Mannosylation in the Murine Brain: Occurrence of Mono-O-Mannosyl Glycans and Identification of New Substrates. 27812179 0 4 theme Glycans 75:81 arg1 Occurrence 45:54 Occurrence 45:54 Occurrence of Mono-O-Mannosyl Glycans 45:81 Protein O-Mannosylation in the Murine Brain: Occurrence of Mono-O-Mannosyl Glycans and Identification of New Substrates. 27812179 0 5 from O-Mannosylation 8:22 arg1 Brain 38:42 the Murine Brain 27:42 the Murine Brain 27:42 Protein O-Mannosylation in the Murine Brain: Occurrence of Mono-O-Mannosyl Glycans and Identification of New Substrates. 27812179 5 6 theme Detailed 691:698 arg1 characterization 700:715 Detailed characterization 691:715 Detailed characterization of clone RKU-1-3-5 691:734 Detailed characterization of clone RKU-1-3-5 revealed that this monoclonal antibody recognizes O-linked mannose also in different peptide and protein contexts. 27812179 8 7 theme superfamilies 1252:1264 arg1 members 1217:1223 members 1217:1223 members of the cadherin and plexin superfamilies 1217:1264 Among the candidates identified are members of the cadherin and plexin superfamilies and the perineural net protein neurocan. 27812179 8 7 theme superfamilies 1252:1264 arg1 neurocan 1297:1304 the perineural net protein neurocan 1270:1304 the perineural net protein neurocan 1270:1304 Among the candidates identified are members of the cadherin and plexin superfamilies and the perineural net protein neurocan. 27812179 1 8 theme essential 182:190 arg1 O-mannosylation 129:143 Protein O-mannosylation 121:143 Protein O-mannosylation 121:143 Protein O-mannosylation is a post-translational modification essential for correct development of mammals. 27812179 1 8 theme essential 182:190 arg1 modification 169:180 a post-translational modification 148:180 a post-translational modification essential for correct development of mammals 148:225 Protein O-mannosylation is a post-translational modification essential for correct development of mammals. 27812179 6 9 theme murine 943:948 arg1 brain 950:954 the murine brain 939:954 the murine brain 939:954 Using this tool, we observed that mono-O-mannosyl glycans occur ubiquitously throughout the murine brain but are especially enriched at inhibitory GABAergic neurons and at the perineural nets. 27812179 5 10 theme O-linked 786:793 arg1 mannose 795:801 O-linked mannose 786:801 O-linked mannose 786:801 Detailed characterization of clone RKU-1-3-5 revealed that this monoclonal antibody recognizes O-linked mannose also in different peptide and protein contexts. 27812179 3 11 from distribution 460:471 arg1 brain 512:516 the mammalian brain 498:516 the mammalian brain 498:516 Although various O-mannosylated proteins have been identified in the recent years, the distribution of O-mannosyl glycans in the mammalian brain and target proteins are still not well defined. 27812179 4 12 theme O-mannosylated 638:651 arg1 AV 672:673 the O-mannosylated peptide YAT(α1-Man)AV 634:673 the O-mannosylated peptide YAT(α1-Man)AV 634:673 In the present study, rabbit monoclonal antibodies directed against the O-mannosylated peptide YAT(α1-Man)AV were generated. 27812179 9 13 theme synaptic 1382:1389 arg1 plasticity 1391:1400 synaptic plasticity 1382:1400 synaptic plasticity 1382:1400 In addition, we identified neurexin 3, a cell adhesion protein involved in synaptic plasticity, and inter-alpha-trypsin inhibitor 5, a protease inhibitor important in stabilizing the extracellular matrix, as new O-mannosylated glycoproteins. 27812179 9 14 theme inter-alpha-trypsin 1407:1425 arg1 neurexin 1334:1341 neurexin 3 1334:1343 neurexin 3 1334:1343 In addition, we identified neurexin 3, a cell adhesion protein involved in synaptic plasticity, and inter-alpha-trypsin inhibitor 5, a protease inhibitor important in stabilizing the extracellular matrix, as new O-mannosylated glycoproteins. 27812179 9 14 theme inter-alpha-trypsin 1407:1425 arg1 inhibitor 1451:1459 a protease inhibitor 1440:1459 a protease inhibitor important in stabilizing the extracellular matrix 1440:1509 In addition, we identified neurexin 3, a cell adhesion protein involved in synaptic plasticity, and inter-alpha-trypsin inhibitor 5, a protease inhibitor important in stabilizing the extracellular matrix, as new O-mannosylated glycoproteins. 27812179 9 14 theme inter-alpha-trypsin 1407:1425 arg1 inhibitor 1427:1435 inter-alpha-trypsin inhibitor 5 1407:1437 inter-alpha-trypsin inhibitor 5 1407:1437 In addition, we identified neurexin 3, a cell adhesion protein involved in synaptic plasticity, and inter-alpha-trypsin inhibitor 5, a protease inhibitor important in stabilizing the extracellular matrix, as new O-mannosylated glycoproteins. 27812179 9 14 theme inter-alpha-trypsin 1407:1425 arg1 glycoproteins 1534:1546 new O-mannosylated glycoproteins 1515:1546 new O-mannosylated glycoproteins 1515:1546 In addition, we identified neurexin 3, a cell adhesion protein involved in synaptic plasticity, and inter-alpha-trypsin inhibitor 5, a protease inhibitor important in stabilizing the extracellular matrix, as new O-mannosylated glycoproteins. 27812179 5 15 theme different 811:819 arg1 peptide 821:827 different peptide and protein contexts 811:848 peptide 821:827 Detailed characterization of clone RKU-1-3-5 revealed that this monoclonal antibody recognizes O-linked mannose also in different peptide and protein contexts. 27812179 9 16 theme new 1515:1517 arg1 neurexin 1334:1341 neurexin 3 1334:1343 neurexin 3 1334:1343 In addition, we identified neurexin 3, a cell adhesion protein involved in synaptic plasticity, and inter-alpha-trypsin inhibitor 5, a protease inhibitor important in stabilizing the extracellular matrix, as new O-mannosylated glycoproteins. 27812179 9 16 theme new 1515:1517 arg1 glycoproteins 1534:1546 new O-mannosylated glycoproteins 1515:1546 new O-mannosylated glycoproteins 1515:1546 In addition, we identified neurexin 3, a cell adhesion protein involved in synaptic plasticity, and inter-alpha-trypsin inhibitor 5, a protease inhibitor important in stabilizing the extracellular matrix, as new O-mannosylated glycoproteins. 27812179 9 16 theme new 1515:1517 arg1 inhibitor 1427:1435 inter-alpha-trypsin inhibitor 5 1407:1437 inter-alpha-trypsin inhibitor 5 1407:1437 In addition, we identified neurexin 3, a cell adhesion protein involved in synaptic plasticity, and inter-alpha-trypsin inhibitor 5, a protease inhibitor important in stabilizing the extracellular matrix, as new O-mannosylated glycoproteins. 27812179 0 17 theme Substrates 109:118 arg1 Identification 87:100 Identification 87:100 Identification of New Substrates 87:118 Protein O-Mannosylation in the Murine Brain: Occurrence of Mono-O-Mannosyl Glycans and Identification of New Substrates. 27812179 0 17 theme Substrates 109:118 arg1 Occurrence 45:54 Occurrence 45:54 Occurrence of Mono-O-Mannosyl Glycans 45:81 Protein O-Mannosylation in the Murine Brain: Occurrence of Mono-O-Mannosyl Glycans and Identification of New Substrates. 27812179 5 18 link O-linked 786:793 arg1 mannose 795:801 O-linked mannose 786:801 O-linked mannose 786:801 Detailed characterization of clone RKU-1-3-5 revealed that this monoclonal antibody recognizes O-linked mannose also in different peptide and protein contexts. 27812179 3 19 theme glycans 487:493 arg1 proteins 529:536 target proteins 522:536 target proteins 522:536 Although various O-mannosylated proteins have been identified in the recent years, the distribution of O-mannosyl glycans in the mammalian brain and target proteins are still not well defined. 27812179 3 19 theme glycans 487:493 arg1 distribution 460:471 the distribution 456:471 the distribution of O-mannosyl glycans in the mammalian brain 456:516 Although various O-mannosylated proteins have been identified in the recent years, the distribution of O-mannosyl glycans in the mammalian brain and target proteins are still not well defined. 27812179 0 20 theme New 105:107 arg1 Substrates 109:118 New Substrates 105:118 New Substrates 105:118 Protein O-Mannosylation in the Murine Brain: Occurrence of Mono-O-Mannosyl Glycans and Identification of New Substrates. 27812179 7 21 theme single 1154:1159 arg1 residues 1171:1178 single O-mannose residues 1154:1178 single O-mannose residues 1154:1178 Using a mass spectrometry-based approach, we further identified glycoproteins from the murine brain that bear single O-mannose residues. 27812179 3 22 theme recent 442:447 arg1 years 449:453 the recent years 438:453 the recent years 438:453 Although various O-mannosylated proteins have been identified in the recent years, the distribution of O-mannosyl glycans in the mammalian brain and target proteins are still not well defined. 27812179 1 23 theme correct 196:202 arg1 development 204:214 correct development 196:214 correct development of mammals 196:225 Protein O-mannosylation is a post-translational modification essential for correct development of mammals. 27812179 8 24 theme perineural 1274:1283 arg1 neurocan 1297:1304 the perineural net protein neurocan 1270:1304 the perineural net protein neurocan 1270:1304 Among the candidates identified are members of the cadherin and plexin superfamilies and the perineural net protein neurocan. 27812179 5 25 theme protein 833:839 arg1 contexts 841:848 different peptide and protein contexts 811:848 contexts 841:848 Detailed characterization of clone RKU-1-3-5 revealed that this monoclonal antibody recognizes O-linked mannose also in different peptide and protein contexts. 27812179 7 26 theme O-mannose 1161:1169 arg1 residues 1171:1178 single O-mannose residues 1154:1178 single O-mannose residues 1154:1178 Using a mass spectrometry-based approach, we further identified glycoproteins from the murine brain that bear single O-mannose residues. 27812179 3 27 from proteins 529:536 arg1 brain 512:516 the mammalian brain 498:516 the mammalian brain 498:516 Although various O-mannosylated proteins have been identified in the recent years, the distribution of O-mannosyl glycans in the mammalian brain and target proteins are still not well defined. 27812179 2 28 theme eye 356:358 arg1 development 360:370 impaired brain and eye development 337:370 development 360:370 In humans, deficient O-mannosylation results in severe congenital muscular dystrophies often associated with impaired brain and eye development. 27812179 7 29 theme murine 1131:1136 arg1 brain 1138:1142 the murine brain 1127:1142 the murine brain 1127:1142 Using a mass spectrometry-based approach, we further identified glycoproteins from the murine brain that bear single O-mannose residues. 27812179 0 30 theme Protein 0:6 arg1 O-Mannosylation 8:22 Protein O-Mannosylation 0:22 Protein O-Mannosylation in the Murine Brain: Occurrence of Mono-O-Mannosyl Glycans and Identification of New Substrates. 0:119 Protein O-Mannosylation in the Murine Brain: Occurrence of Mono-O-Mannosyl Glycans and Identification of New Substrates. 27812179 4 31 theme rabbit 588:593 arg1 antibodies 606:615 rabbit monoclonal antibodies 588:615 rabbit monoclonal antibodies directed against the O-mannosylated peptide YAT(α1-Man)AV 588:673 In the present study, rabbit monoclonal antibodies directed against the O-mannosylated peptide YAT(α1-Man)AV were generated. 27812179 3 32 theme O-mannosyl 476:485 arg1 glycans 487:493 O-mannosyl glycans 476:493 O-mannosyl glycans 476:493 Although various O-mannosylated proteins have been identified in the recent years, the distribution of O-mannosyl glycans in the mammalian brain and target proteins are still not well defined. 27812179 8 33 theme protein 1289:1295 arg1 neurocan 1297:1304 the perineural net protein neurocan 1270:1304 the perineural net protein neurocan 1270:1304 Among the candidates identified are members of the cadherin and plexin superfamilies and the perineural net protein neurocan. 27812179 2 34 theme severe 276:281 arg1 dystrophies 303:313 severe congenital muscular dystrophies 276:313 severe congenital muscular dystrophies often associated with impaired brain and eye development 276:370 In humans, deficient O-mannosylation results in severe congenital muscular dystrophies often associated with impaired brain and eye development. 27812179 6 35 from nets 1038:1041 arg1 enriched 975:982 enriched 975:982 enriched 975:982 Using this tool, we observed that mono-O-mannosyl glycans occur ubiquitously throughout the murine brain but are especially enriched at inhibitory GABAergic neurons and at the perineural nets. 27812179 4 36 gly O-mannosylated 638:651 arg1 AV 672:673 the O-mannosylated peptide YAT(α1-Man)AV 634:673 the O-mannosylated peptide YAT(α1-Man)AV 634:673 In the present study, rabbit monoclonal antibodies directed against the O-mannosylated peptide YAT(α1-Man)AV were generated. 27812179 9 37 gly glycoproteins 1534:1546 arg1 neurexin 1334:1341 neurexin 3 1334:1343 neurexin 3 1334:1343 In addition, we identified neurexin 3, a cell adhesion protein involved in synaptic plasticity, and inter-alpha-trypsin inhibitor 5, a protease inhibitor important in stabilizing the extracellular matrix, as new O-mannosylated glycoproteins. 27812179 9 37 gly glycoproteins 1534:1546 arg1 glycoproteins 1534:1546 new O-mannosylated glycoproteins 1515:1546 new O-mannosylated glycoproteins 1515:1546 In addition, we identified neurexin 3, a cell adhesion protein involved in synaptic plasticity, and inter-alpha-trypsin inhibitor 5, a protease inhibitor important in stabilizing the extracellular matrix, as new O-mannosylated glycoproteins. 27812179 9 37 gly glycoproteins 1534:1546 arg1 inhibitor 1427:1435 inter-alpha-trypsin inhibitor 5 1407:1437 inter-alpha-trypsin inhibitor 5 1407:1437 In addition, we identified neurexin 3, a cell adhesion protein involved in synaptic plasticity, and inter-alpha-trypsin inhibitor 5, a protease inhibitor important in stabilizing the extracellular matrix, as new O-mannosylated glycoproteins. 27812179 9 38 theme important 1461:1469 arg1 inhibitor 1451:1459 a protease inhibitor 1440:1459 a protease inhibitor important in stabilizing the extracellular matrix 1440:1509 In addition, we identified neurexin 3, a cell adhesion protein involved in synaptic plasticity, and inter-alpha-trypsin inhibitor 5, a protease inhibitor important in stabilizing the extracellular matrix, as new O-mannosylated glycoproteins. 27812179 9 38 theme important 1461:1469 arg1 inhibitor 1427:1435 inter-alpha-trypsin inhibitor 5 1407:1437 inter-alpha-trypsin inhibitor 5 1407:1437 In addition, we identified neurexin 3, a cell adhesion protein involved in synaptic plasticity, and inter-alpha-trypsin inhibitor 5, a protease inhibitor important in stabilizing the extracellular matrix, as new O-mannosylated glycoproteins. 27812179 1 39 theme mammals 219:225 arg1 development 204:214 correct development 196:214 correct development of mammals 196:225 Protein O-mannosylation is a post-translational modification essential for correct development of mammals. 27812179 8 40 theme net 1285:1287 arg1 neurocan 1297:1304 the perineural net protein neurocan 1270:1304 the perineural net protein neurocan 1270:1304 Among the candidates identified are members of the cadherin and plexin superfamilies and the perineural net protein neurocan. 27812179 5 41 theme monoclonal 755:764 arg1 antibody 766:773 this monoclonal antibody 750:773 this monoclonal antibody 750:773 Detailed characterization of clone RKU-1-3-5 revealed that this monoclonal antibody recognizes O-linked mannose also in different peptide and protein contexts. 27812179 3 42 theme O-mannosylated 390:403 arg1 proteins 405:412 various O-mannosylated proteins 382:412 various O-mannosylated proteins 382:412 Although various O-mannosylated proteins have been identified in the recent years, the distribution of O-mannosyl glycans in the mammalian brain and target proteins are still not well defined. 27812179 2 43 theme impaired 337:344 arg1 brain 346:350 impaired brain and eye development 337:370 brain 346:350 In humans, deficient O-mannosylation results in severe congenital muscular dystrophies often associated with impaired brain and eye development. 27812179 9 44 theme adhesion 1353:1360 arg1 neurexin 1334:1341 neurexin 3 1334:1343 neurexin 3 1334:1343 In addition, we identified neurexin 3, a cell adhesion protein involved in synaptic plasticity, and inter-alpha-trypsin inhibitor 5, a protease inhibitor important in stabilizing the extracellular matrix, as new O-mannosylated glycoproteins. 27812179 9 44 theme adhesion 1353:1360 arg1 protein 1362:1368 a cell adhesion protein 1346:1368 a cell adhesion protein involved in synaptic plasticity 1346:1400 In addition, we identified neurexin 3, a cell adhesion protein involved in synaptic plasticity, and inter-alpha-trypsin inhibitor 5, a protease inhibitor important in stabilizing the extracellular matrix, as new O-mannosylated glycoproteins. 27812179 4 45 theme monoclonal 595:604 arg1 antibodies 606:615 rabbit monoclonal antibodies 588:615 rabbit monoclonal antibodies directed against the O-mannosylated peptide YAT(α1-Man)AV 588:673 In the present study, rabbit monoclonal antibodies directed against the O-mannosylated peptide YAT(α1-Man)AV were generated. 27812179 9 46 gly O-mannosylated 1519:1532 arg1 neurexin 1334:1341 neurexin 3 1334:1343 neurexin 3 1334:1343 In addition, we identified neurexin 3, a cell adhesion protein involved in synaptic plasticity, and inter-alpha-trypsin inhibitor 5, a protease inhibitor important in stabilizing the extracellular matrix, as new O-mannosylated glycoproteins. 27812179 9 46 gly O-mannosylated 1519:1532 arg1 glycoproteins 1534:1546 new O-mannosylated glycoproteins 1515:1546 new O-mannosylated glycoproteins 1515:1546 In addition, we identified neurexin 3, a cell adhesion protein involved in synaptic plasticity, and inter-alpha-trypsin inhibitor 5, a protease inhibitor important in stabilizing the extracellular matrix, as new O-mannosylated glycoproteins. 27812179 9 46 gly O-mannosylated 1519:1532 arg1 inhibitor 1427:1435 inter-alpha-trypsin inhibitor 5 1407:1437 inter-alpha-trypsin inhibitor 5 1407:1437 In addition, we identified neurexin 3, a cell adhesion protein involved in synaptic plasticity, and inter-alpha-trypsin inhibitor 5, a protease inhibitor important in stabilizing the extracellular matrix, as new O-mannosylated glycoproteins. 27812179 6 47 theme perineural 1027:1036 arg1 nets 1038:1041 the perineural nets 1023:1041 the perineural nets 1023:1041 Using this tool, we observed that mono-O-mannosyl glycans occur ubiquitously throughout the murine brain but are especially enriched at inhibitory GABAergic neurons and at the perineural nets. 27812179 7 48 contain bear 1149:1152 arg1 glycoproteins 1108:1120 glycoproteins 1108:1120 glycoproteins from the murine brain that bear single O-mannose residues 1108:1178 Using a mass spectrometry-based approach, we further identified glycoproteins from the murine brain that bear single O-mannose residues. 27812179 7 48 contain bear 1149:1152 arg2 residues 1171:1178 single O-mannose residues 1154:1178 single O-mannose residues 1154:1178 Using a mass spectrometry-based approach, we further identified glycoproteins from the murine brain that bear single O-mannose residues. 27812179 0 49 theme Murine 31:36 arg1 Brain 38:42 the Murine Brain 27:42 the Murine Brain 27:42 Protein O-Mannosylation in the Murine Brain: Occurrence of Mono-O-Mannosyl Glycans and Identification of New Substrates. 27812179 3 50 gly O-mannosylated 390:403 arg1 proteins 405:412 various O-mannosylated proteins 382:412 various O-mannosylated proteins 382:412 Although various O-mannosylated proteins have been identified in the recent years, the distribution of O-mannosyl glycans in the mammalian brain and target proteins are still not well defined. 27812179 3 51 theme mammalian 502:510 arg1 brain 512:516 the mammalian brain 498:516 the mammalian brain 498:516 Although various O-mannosylated proteins have been identified in the recent years, the distribution of O-mannosyl glycans in the mammalian brain and target proteins are still not well defined. 27812179 8 52 theme plexin 1245:1250 arg1 superfamilies 1252:1264 the cadherin and plexin superfamilies 1228:1264 the cadherin and plexin superfamilies 1228:1264 Among the candidates identified are members of the cadherin and plexin superfamilies and the perineural net protein neurocan. 27812179 5 53 theme clone 720:724 arg1 characterization 700:715 Detailed characterization 691:715 Detailed characterization of clone RKU-1-3-5 691:734 Detailed characterization of clone RKU-1-3-5 revealed that this monoclonal antibody recognizes O-linked mannose also in different peptide and protein contexts. 27812179 2 54 theme deficient 239:247 arg1 O-mannosylation 249:263 deficient O-mannosylation 239:263 deficient O-mannosylation 239:263 In humans, deficient O-mannosylation results in severe congenital muscular dystrophies often associated with impaired brain and eye development. 27812179 9 55 theme O-mannosylated 1519:1532 arg1 neurexin 1334:1341 neurexin 3 1334:1343 neurexin 3 1334:1343 In addition, we identified neurexin 3, a cell adhesion protein involved in synaptic plasticity, and inter-alpha-trypsin inhibitor 5, a protease inhibitor important in stabilizing the extracellular matrix, as new O-mannosylated glycoproteins. 27812179 9 55 theme O-mannosylated 1519:1532 arg1 glycoproteins 1534:1546 new O-mannosylated glycoproteins 1515:1546 new O-mannosylated glycoproteins 1515:1546 In addition, we identified neurexin 3, a cell adhesion protein involved in synaptic plasticity, and inter-alpha-trypsin inhibitor 5, a protease inhibitor important in stabilizing the extracellular matrix, as new O-mannosylated glycoproteins. 27812179 9 55 theme O-mannosylated 1519:1532 arg1 inhibitor 1427:1435 inter-alpha-trypsin inhibitor 5 1407:1437 inter-alpha-trypsin inhibitor 5 1407:1437 In addition, we identified neurexin 3, a cell adhesion protein involved in synaptic plasticity, and inter-alpha-trypsin inhibitor 5, a protease inhibitor important in stabilizing the extracellular matrix, as new O-mannosylated glycoproteins. 27812179 6 56 from neurons 1008:1014 arg1 enriched 975:982 enriched 975:982 enriched 975:982 Using this tool, we observed that mono-O-mannosyl glycans occur ubiquitously throughout the murine brain but are especially enriched at inhibitory GABAergic neurons and at the perineural nets. 27812179 1 57 theme Protein 121:127 arg1 O-mannosylation 129:143 Protein O-mannosylation 121:143 Protein O-mannosylation 121:143 Protein O-mannosylation is a post-translational modification essential for correct development of mammals. 27812179 1 57 theme Protein 121:127 arg1 modification 169:180 a post-translational modification 148:180 a post-translational modification essential for correct development of mammals 148:225 Protein O-mannosylation is a post-translational modification essential for correct development of mammals. 27812179 4 58 theme present 573:579 arg1 study 581:585 the present study 569:585 the present study 569:585 In the present study, rabbit monoclonal antibodies directed against the O-mannosylated peptide YAT(α1-Man)AV were generated. 27812179 2 59 theme muscular 294:301 arg1 dystrophies 303:313 severe congenital muscular dystrophies 276:313 severe congenital muscular dystrophies often associated with impaired brain and eye development 276:370 In humans, deficient O-mannosylation results in severe congenital muscular dystrophies often associated with impaired brain and eye development. 27812179 3 60 theme target 522:527 arg1 proteins 529:536 target proteins 522:536 target proteins 522:536 Although various O-mannosylated proteins have been identified in the recent years, the distribution of O-mannosyl glycans in the mammalian brain and target proteins are still not well defined. 27812179 4 61 theme YAT 661:663 arg1 AV 672:673 the O-mannosylated peptide YAT(α1-Man)AV 634:673 the O-mannosylated peptide YAT(α1-Man)AV 634:673 In the present study, rabbit monoclonal antibodies directed against the O-mannosylated peptide YAT(α1-Man)AV were generated. 27812179 6 62 theme mono-O-mannosyl 885:899 arg1 glycans 901:907 mono-O-mannosyl glycans 885:907 mono-O-mannosyl glycans 885:907 Using this tool, we observed that mono-O-mannosyl glycans occur ubiquitously throughout the murine brain but are especially enriched at inhibitory GABAergic neurons and at the perineural nets. 27812179 2 63 theme congenital 283:292 arg1 dystrophies 303:313 severe congenital muscular dystrophies 276:313 severe congenital muscular dystrophies often associated with impaired brain and eye development 276:370 In humans, deficient O-mannosylation results in severe congenital muscular dystrophies often associated with impaired brain and eye development. 27812179 7 64 theme spectrometry-based 1057:1074 arg1 approach 1076:1083 a mass spectrometry-based approach 1050:1083 a mass spectrometry-based approach 1050:1083 Using a mass spectrometry-based approach, we further identified glycoproteins from the murine brain that bear single O-mannose residues. 27812179 7 65 gly glycoproteins 1108:1120 arg1 glycoproteins 1108:1120 glycoproteins 1108:1120 glycoproteins from the murine brain that bear single O-mannose residues 1108:1178 Using a mass spectrometry-based approach, we further identified glycoproteins from the murine brain that bear single O-mannose residues. 27812179 4 66 theme peptide 653:659 arg1 AV 672:673 the O-mannosylated peptide YAT(α1-Man)AV 634:673 the O-mannosylated peptide YAT(α1-Man)AV 634:673 In the present study, rabbit monoclonal antibodies directed against the O-mannosylated peptide YAT(α1-Man)AV were generated. 27812179 0 67 theme Mono-O-Mannosyl 59:73 arg1 Glycans 75:81 Mono-O-Mannosyl Glycans 59:81 Mono-O-Mannosyl Glycans 59:81 Protein O-Mannosylation in the Murine Brain: Occurrence of Mono-O-Mannosyl Glycans and Identification of New Substrates. 27812179 9 68 theme cell 1348:1351 arg1 neurexin 1334:1341 neurexin 3 1334:1343 neurexin 3 1334:1343 In addition, we identified neurexin 3, a cell adhesion protein involved in synaptic plasticity, and inter-alpha-trypsin inhibitor 5, a protease inhibitor important in stabilizing the extracellular matrix, as new O-mannosylated glycoproteins. 27812179 9 68 theme cell 1348:1351 arg1 protein 1362:1368 a cell adhesion protein 1346:1368 a cell adhesion protein involved in synaptic plasticity 1346:1400 In addition, we identified neurexin 3, a cell adhesion protein involved in synaptic plasticity, and inter-alpha-trypsin inhibitor 5, a protease inhibitor important in stabilizing the extracellular matrix, as new O-mannosylated glycoproteins. 27812179 0 69 dep O-Mannosylation 8:22 arg1 Identification 87:100 Identification 87:100 Identification of New Substrates 87:118 Protein O-Mannosylation in the Murine Brain: Occurrence of Mono-O-Mannosyl Glycans and Identification of New Substrates. 27812179 0 69 dep O-Mannosylation 8:22 arg1 Occurrence 45:54 Occurrence 45:54 Occurrence of Mono-O-Mannosyl Glycans 45:81 Protein O-Mannosylation in the Murine Brain: Occurrence of Mono-O-Mannosyl Glycans and Identification of New Substrates. 27812179 4 70 theme α1-Man 665:670 arg1 AV 672:673 the O-mannosylated peptide YAT(α1-Man)AV 634:673 the O-mannosylated peptide YAT(α1-Man)AV 634:673 In the present study, rabbit monoclonal antibodies directed against the O-mannosylated peptide YAT(α1-Man)AV were generated. 27812179 3 71 theme various 382:388 arg1 proteins 405:412 various O-mannosylated proteins 382:412 various O-mannosylated proteins 382:412 Although various O-mannosylated proteins have been identified in the recent years, the distribution of O-mannosyl glycans in the mammalian brain and target proteins are still not well defined. 27812179 6 72 theme GABAergic 998:1006 arg1 neurons 1008:1014 inhibitory GABAergic neurons 987:1014 inhibitory GABAergic neurons 987:1014 Using this tool, we observed that mono-O-mannosyl glycans occur ubiquitously throughout the murine brain but are especially enriched at inhibitory GABAergic neurons and at the perineural nets. 27812179 9 73 theme extracellular 1490:1502 arg1 matrix 1504:1509 the extracellular matrix 1486:1509 the extracellular matrix 1486:1509 In addition, we identified neurexin 3, a cell adhesion protein involved in synaptic plasticity, and inter-alpha-trypsin inhibitor 5, a protease inhibitor important in stabilizing the extracellular matrix, as new O-mannosylated glycoproteins. 27812179 1 74 theme post-translational 150:167 arg1 O-mannosylation 129:143 Protein O-mannosylation 121:143 Protein O-mannosylation 121:143 Protein O-mannosylation is a post-translational modification essential for correct development of mammals. 27812179 1 74 theme post-translational 150:167 arg1 modification 169:180 a post-translational modification 148:180 a post-translational modification essential for correct development of mammals 148:225 Protein O-mannosylation is a post-translational modification essential for correct development of mammals. 27812179 9 75 theme protease 1442:1449 arg1 inhibitor 1451:1459 a protease inhibitor 1440:1459 a protease inhibitor important in stabilizing the extracellular matrix 1440:1509 In addition, we identified neurexin 3, a cell adhesion protein involved in synaptic plasticity, and inter-alpha-trypsin inhibitor 5, a protease inhibitor important in stabilizing the extracellular matrix, as new O-mannosylated glycoproteins. 27812179 9 75 theme protease 1442:1449 arg1 inhibitor 1427:1435 inter-alpha-trypsin inhibitor 5 1407:1437 inter-alpha-trypsin inhibitor 5 1407:1437 In addition, we identified neurexin 3, a cell adhesion protein involved in synaptic plasticity, and inter-alpha-trypsin inhibitor 5, a protease inhibitor important in stabilizing the extracellular matrix, as new O-mannosylated glycoproteins. 26640786 2 0 with modification 419:430 arg1 N-acetylglucosamine 458:476 O-linked N-acetylglucosamine 449:476 O-linked N-acetylglucosamine (O-GlcNAcylation) 449:494 This study aims to characterize cellular senescence at the level of global protein expression profiles and modification of proteins with O-linked N-acetylglucosamine (O-GlcNAcylation). 26640786 2 0 with modification 419:430 arg1 O-GlcNAcylation 479:493 O-GlcNAcylation 479:493 O-GlcNAcylation 479:493 This study aims to characterize cellular senescence at the level of global protein expression profiles and modification of proteins with O-linked N-acetylglucosamine (O-GlcNAcylation). 26640786 4 1 theme O-GlcNAc 666:673 arg1 status 675:680 O-GlcNAc status 666:680 O-GlcNAc status 666:680 O-GlcNAc status was assessed by Western blot under normal conditions and after modulation with 6-diazo-5-oxo-L-norleucine (DON) to decrease O-GlcNAcylation or O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc) to increase O-GlcNAcylation. 26640786 2 2 theme protein 387:393 arg1 profiles 406:413 global protein expression profiles 380:413 global protein expression profiles 380:413 This study aims to characterize cellular senescence at the level of global protein expression profiles and modification of proteins with O-linked N-acetylglucosamine (O-GlcNAcylation). 26640786 1 3 theme peritoneal 291:300 arg1 dialysis 302:309 peritoneal dialysis 291:309 peritoneal dialysis 291:309 INTRODUCTION Senescence of peritoneal mesothelial cells represents a biological program defined by arrested cell growth and altered cell secretory phenotype with potential impact in peritoneal dialysis. 26640786 7 4 theme regulation 1499:1508 arg1 proteome 1457:1464 proteome 1457:1464 proteome 1457:1464 DISCUSSION This study identified changes of the proteome and altered dynamics of O-GlcNAc regulation in senescent mesothelial cells. 26640786 7 4 theme regulation 1499:1508 arg1 dynamics 1478:1485 altered dynamics 1470:1485 altered dynamics 1470:1485 DISCUSSION This study identified changes of the proteome and altered dynamics of O-GlcNAc regulation in senescent mesothelial cells. 26640786 3 5 theme peritoneal 573:582 arg1 HPMC 603:606 HPMC 603:606 HPMC 603:606 METHODS A comparative proteomics analysis between young and senescent human peritoneal mesothelial cells (HPMC) was performed using two-dimensional gel electrophoresis. 26640786 3 5 theme peritoneal 573:582 arg1 cells 596:600 human peritoneal mesothelial cells 567:600 human peritoneal mesothelial cells (HPMC) 567:607 METHODS A comparative proteomics analysis between young and senescent human peritoneal mesothelial cells (HPMC) was performed using two-dimensional gel electrophoresis. 26640786 5 6 theme spots 1044:1048 arg1 11 1051:1052 11 1051:1052 11 1051:1052 RESULTS Comparison of protein pattern of senescent and young HPMC revealed 29 differentially abundant protein spots, 11 of which were identified to be actin (cytoplasmic 1 and 2), cytokeratin-7, cofilin-2, transgelin-2, Hsp60, Hsc70, proteasome β-subunits (type-2 and type-3), nucleoside diphosphate kinase A, and cytosolic 5'(3')-deoxyribonucleotidase. 26640786 5 6 theme spots 1044:1048 arg1 spots 1044:1048 29 differentially abundant protein spots 1009:1048 29 differentially abundant protein spots 1009:1048 RESULTS Comparison of protein pattern of senescent and young HPMC revealed 29 differentially abundant protein spots, 11 of which were identified to be actin (cytoplasmic 1 and 2), cytokeratin-7, cofilin-2, transgelin-2, Hsp60, Hsc70, proteasome β-subunits (type-2 and type-3), nucleoside diphosphate kinase A, and cytosolic 5'(3')-deoxyribonucleotidase. 26640786 1 7 theme arrested 208:215 arg1 growth 222:227 arrested cell growth 208:227 arrested cell growth 208:227 INTRODUCTION Senescence of peritoneal mesothelial cells represents a biological program defined by arrested cell growth and altered cell secretory phenotype with potential impact in peritoneal dialysis. 26640786 7 8 theme mesothelial 1523:1533 arg1 cells 1535:1539 senescent mesothelial cells 1513:1539 senescent mesothelial cells 1513:1539 DISCUSSION This study identified changes of the proteome and altered dynamics of O-GlcNAc regulation in senescent mesothelial cells. 26640786 7 9 theme altered 1470:1476 arg1 dynamics 1478:1485 altered dynamics 1470:1485 altered dynamics 1470:1485 DISCUSSION This study identified changes of the proteome and altered dynamics of O-GlcNAc regulation in senescent mesothelial cells. 26640786 6 10 theme global 1301:1306 arg1 comparable 1337:1346 comparable 1337:1346 comparable 1337:1346 Although the global level of O-GlcNAcylation was comparable, senescent cells were not sensitive to modulation by PUGNAc. 26640786 6 10 theme global 1301:1306 arg1 level 1308:1312 the global level 1297:1312 the global level of O-GlcNAcylation 1297:1331 Although the global level of O-GlcNAcylation was comparable, senescent cells were not sensitive to modulation by PUGNAc. 26640786 7 11 theme proteome 1457:1464 arg1 changes 1442:1448 changes 1442:1448 changes of the proteome and altered dynamics of O-GlcNAc regulation in senescent mesothelial cells 1442:1539 DISCUSSION This study identified changes of the proteome and altered dynamics of O-GlcNAc regulation in senescent mesothelial cells. 26640786 4 12 theme normal 717:722 arg1 conditions 724:733 normal conditions 717:733 normal conditions 717:733 O-GlcNAc status was assessed by Western blot under normal conditions and after modulation with 6-diazo-5-oxo-L-norleucine (DON) to decrease O-GlcNAcylation or O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc) to increase O-GlcNAcylation. 26640786 1 13 theme secretory 246:254 arg1 phenotype 256:264 altered cell secretory phenotype 233:264 altered cell secretory phenotype 233:264 INTRODUCTION Senescence of peritoneal mesothelial cells represents a biological program defined by arrested cell growth and altered cell secretory phenotype with potential impact in peritoneal dialysis. 26640786 3 14 theme two-dimensional 629:643 arg1 electrophoresis 649:663 two-dimensional gel electrophoresis 629:663 two-dimensional gel electrophoresis 629:663 METHODS A comparative proteomics analysis between young and senescent human peritoneal mesothelial cells (HPMC) was performed using two-dimensional gel electrophoresis. 26640786 5 15 theme pattern 964:970 arg1 Comparison 942:951 Comparison 942:951 Comparison of protein pattern of senescent and young HPMC 942:998 RESULTS Comparison of protein pattern of senescent and young HPMC revealed 29 differentially abundant protein spots, 11 of which were identified to be actin (cytoplasmic 1 and 2), cytokeratin-7, cofilin-2, transgelin-2, Hsp60, Hsc70, proteasome β-subunits (type-2 and type-3), nucleoside diphosphate kinase A, and cytosolic 5'(3')-deoxyribonucleotidase. 26640786 5 16 theme senescent 975:983 arg1 HPMC 995:998 senescent and young HPMC 975:998 senescent and young HPMC 975:998 RESULTS Comparison of protein pattern of senescent and young HPMC revealed 29 differentially abundant protein spots, 11 of which were identified to be actin (cytoplasmic 1 and 2), cytokeratin-7, cofilin-2, transgelin-2, Hsp60, Hsc70, proteasome β-subunits (type-2 and type-3), nucleoside diphosphate kinase A, and cytosolic 5'(3')-deoxyribonucleotidase. 26640786 1 17 from impact 281:286 arg1 dialysis 302:309 peritoneal dialysis 291:309 peritoneal dialysis 291:309 INTRODUCTION Senescence of peritoneal mesothelial cells represents a biological program defined by arrested cell growth and altered cell secretory phenotype with potential impact in peritoneal dialysis. 26640786 1 18 theme mesothelial 147:157 arg1 cells 159:163 peritoneal mesothelial cells 136:163 peritoneal mesothelial cells 136:163 INTRODUCTION Senescence of peritoneal mesothelial cells represents a biological program defined by arrested cell growth and altered cell secretory phenotype with potential impact in peritoneal dialysis. 26640786 4 19 theme O- 825:826 arg1 carbamate 886:894 O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate 825:894 O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc) 825:903 O-GlcNAc status was assessed by Western blot under normal conditions and after modulation with 6-diazo-5-oxo-L-norleucine (DON) to decrease O-GlcNAcylation or O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc) to increase O-GlcNAcylation. 26640786 4 19 theme O- 825:826 arg1 PUGNAc 897:902 PUGNAc 897:902 PUGNAc 897:902 O-GlcNAc status was assessed by Western blot under normal conditions and after modulation with 6-diazo-5-oxo-L-norleucine (DON) to decrease O-GlcNAcylation or O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc) to increase O-GlcNAcylation. 26640786 8 20 from response 1729:1736 arg1 dialysis 1752:1759 peritoneal dialysis 1741:1759 peritoneal dialysis 1741:1759 Whereas changes in cytoskeleton-associated proteins likely reflect altered cell morphology, changes in chaperoning and housekeeping proteins may have functional impact on cellular stress response in peritoneal dialysis. 26640786 7 21 dep DISCUSSION 1409:1418 arg1 identified 1431:1440 identified 1431:1440 identified changes of the proteome and altered dynamics of O-GlcNAc regulation in senescent mesothelial cells 1431:1539 DISCUSSION This study identified changes of the proteome and altered dynamics of O-GlcNAc regulation in senescent mesothelial cells. 26640786 0 22 theme Human 73:77 arg1 Cells 102:106 Human Peritoneal Mesothelial Cells 73:106 Human Peritoneal Mesothelial Cells 73:106 Senescence-Associated Changes in Proteome and O-GlcNAcylation Pattern in Human Peritoneal Mesothelial Cells. 26640786 1 23 theme biological 178:187 arg1 program 189:195 a biological program 176:195 a biological program defined by arrested cell growth and altered cell secretory phenotype with potential impact in peritoneal dialysis 176:309 INTRODUCTION Senescence of peritoneal mesothelial cells represents a biological program defined by arrested cell growth and altered cell secretory phenotype with potential impact in peritoneal dialysis. 26640786 0 24 theme Mesothelial 90:100 arg1 Cells 102:106 Human Peritoneal Mesothelial Cells 73:106 Human Peritoneal Mesothelial Cells 73:106 Senescence-Associated Changes in Proteome and O-GlcNAcylation Pattern in Human Peritoneal Mesothelial Cells. 26640786 5 25 theme protein 1036:1042 arg1 spots 1044:1048 29 differentially abundant protein spots 1009:1048 29 differentially abundant protein spots 1009:1048 RESULTS Comparison of protein pattern of senescent and young HPMC revealed 29 differentially abundant protein spots, 11 of which were identified to be actin (cytoplasmic 1 and 2), cytokeratin-7, cofilin-2, transgelin-2, Hsp60, Hsc70, proteasome β-subunits (type-2 and type-3), nucleoside diphosphate kinase A, and cytosolic 5'(3')-deoxyribonucleotidase. 26640786 8 26 theme cell 1617:1620 arg1 morphology 1622:1631 altered cell morphology 1609:1631 altered cell morphology 1609:1631 Whereas changes in cytoskeleton-associated proteins likely reflect altered cell morphology, changes in chaperoning and housekeeping proteins may have functional impact on cellular stress response in peritoneal dialysis. 26640786 4 27 theme 2-acetamido-2-deoxy-D-glucopyranosylidene 828:868 arg1 carbamate 886:894 O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate 825:894 O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc) 825:903 O-GlcNAc status was assessed by Western blot under normal conditions and after modulation with 6-diazo-5-oxo-L-norleucine (DON) to decrease O-GlcNAcylation or O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc) to increase O-GlcNAcylation. 26640786 4 27 theme 2-acetamido-2-deoxy-D-glucopyranosylidene 828:868 arg1 PUGNAc 897:902 PUGNAc 897:902 PUGNAc 897:902 O-GlcNAc status was assessed by Western blot under normal conditions and after modulation with 6-diazo-5-oxo-L-norleucine (DON) to decrease O-GlcNAcylation or O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc) to increase O-GlcNAcylation. 26640786 0 28 theme Senescence-Associated 0:20 arg1 Changes 22:28 Senescence-Associated Changes 0:28 Senescence-Associated Changes in Proteome and O-GlcNAcylation Pattern in Human Peritoneal Mesothelial Cells. 0:107 Senescence-Associated Changes in Proteome and O-GlcNAcylation Pattern in Human Peritoneal Mesothelial Cells. 26640786 1 29 theme INTRODUCTION 109:120 arg1 Senescence 122:131 INTRODUCTION Senescence 109:131 INTRODUCTION Senescence of peritoneal mesothelial cells 109:163 INTRODUCTION Senescence of peritoneal mesothelial cells represents a biological program defined by arrested cell growth and altered cell secretory phenotype with potential impact in peritoneal dialysis. 26640786 4 30 theme amino 871:875 arg1 carbamate 886:894 O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate 825:894 O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc) 825:903 O-GlcNAc status was assessed by Western blot under normal conditions and after modulation with 6-diazo-5-oxo-L-norleucine (DON) to decrease O-GlcNAcylation or O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc) to increase O-GlcNAcylation. 26640786 4 30 theme amino 871:875 arg1 PUGNAc 897:902 PUGNAc 897:902 PUGNAc 897:902 O-GlcNAc status was assessed by Western blot under normal conditions and after modulation with 6-diazo-5-oxo-L-norleucine (DON) to decrease O-GlcNAcylation or O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc) to increase O-GlcNAcylation. 26640786 5 31 theme 5 1258:1258 arg1 actin 1085:1089 actin 1085:1089 actin (cytoplasmic 1 and 2) 1085:1111 RESULTS Comparison of protein pattern of senescent and young HPMC revealed 29 differentially abundant protein spots, 11 of which were identified to be actin (cytoplasmic 1 and 2), cytokeratin-7, cofilin-2, transgelin-2, Hsp60, Hsc70, proteasome β-subunits (type-2 and type-3), nucleoside diphosphate kinase A, and cytosolic 5'(3')-deoxyribonucleotidase. 26640786 5 31 theme 5 1258:1258 arg1 -deoxyribonucleotidase 1264:1285 cytosolic 5'(3')-deoxyribonucleotidase 1248:1285 cytosolic 5'(3')-deoxyribonucleotidase 1248:1285 RESULTS Comparison of protein pattern of senescent and young HPMC revealed 29 differentially abundant protein spots, 11 of which were identified to be actin (cytoplasmic 1 and 2), cytokeratin-7, cofilin-2, transgelin-2, Hsp60, Hsc70, proteasome β-subunits (type-2 and type-3), nucleoside diphosphate kinase A, and cytosolic 5'(3')-deoxyribonucleotidase. 26640786 3 32 theme comparative 507:517 arg1 analysis 530:537 A comparative proteomics analysis 505:537 METHODS A comparative proteomics analysis between young and senescent human peritoneal mesothelial cells (HPMC) 497:607 METHODS A comparative proteomics analysis between young and senescent human peritoneal mesothelial cells (HPMC) was performed using two-dimensional gel electrophoresis. 26640786 5 33 theme diphosphate 1222:1232 arg1 A 1241:1241 nucleoside diphosphate kinase A 1211:1241 nucleoside diphosphate kinase A 1211:1241 RESULTS Comparison of protein pattern of senescent and young HPMC revealed 29 differentially abundant protein spots, 11 of which were identified to be actin (cytoplasmic 1 and 2), cytokeratin-7, cofilin-2, transgelin-2, Hsp60, Hsc70, proteasome β-subunits (type-2 and type-3), nucleoside diphosphate kinase A, and cytosolic 5'(3')-deoxyribonucleotidase. 26640786 5 33 theme diphosphate 1222:1232 arg1 actin 1085:1089 actin 1085:1089 actin (cytoplasmic 1 and 2) 1085:1111 RESULTS Comparison of protein pattern of senescent and young HPMC revealed 29 differentially abundant protein spots, 11 of which were identified to be actin (cytoplasmic 1 and 2), cytokeratin-7, cofilin-2, transgelin-2, Hsp60, Hsc70, proteasome β-subunits (type-2 and type-3), nucleoside diphosphate kinase A, and cytosolic 5'(3')-deoxyribonucleotidase. 26640786 2 34 theme global 380:385 arg1 profiles 406:413 global protein expression profiles 380:413 global protein expression profiles 380:413 This study aims to characterize cellular senescence at the level of global protein expression profiles and modification of proteins with O-linked N-acetylglucosamine (O-GlcNAcylation). 26640786 1 35 with growth 222:227 arg1 impact 281:286 potential impact 271:286 potential impact in peritoneal dialysis 271:309 INTRODUCTION Senescence of peritoneal mesothelial cells represents a biological program defined by arrested cell growth and altered cell secretory phenotype with potential impact in peritoneal dialysis. 26640786 2 36 link O-linked 449:456 arg1 N-acetylglucosamine 458:476 O-linked N-acetylglucosamine 449:476 O-linked N-acetylglucosamine (O-GlcNAcylation) 449:494 This study aims to characterize cellular senescence at the level of global protein expression profiles and modification of proteins with O-linked N-acetylglucosamine (O-GlcNAcylation). 26640786 2 36 link O-linked 449:456 arg1 O-GlcNAcylation 479:493 O-GlcNAcylation 479:493 O-GlcNAcylation 479:493 This study aims to characterize cellular senescence at the level of global protein expression profiles and modification of proteins with O-linked N-acetylglucosamine (O-GlcNAcylation). 26640786 2 37 theme O-linked 449:456 arg1 N-acetylglucosamine 458:476 O-linked N-acetylglucosamine 449:476 O-linked N-acetylglucosamine (O-GlcNAcylation) 449:494 This study aims to characterize cellular senescence at the level of global protein expression profiles and modification of proteins with O-linked N-acetylglucosamine (O-GlcNAcylation). 26640786 2 37 theme O-linked 449:456 arg1 O-GlcNAcylation 479:493 O-GlcNAcylation 479:493 O-GlcNAcylation 479:493 This study aims to characterize cellular senescence at the level of global protein expression profiles and modification of proteins with O-linked N-acetylglucosamine (O-GlcNAcylation). 26640786 5 38 theme young 989:993 arg1 HPMC 995:998 senescent and young HPMC 975:998 senescent and young HPMC 975:998 RESULTS Comparison of protein pattern of senescent and young HPMC revealed 29 differentially abundant protein spots, 11 of which were identified to be actin (cytoplasmic 1 and 2), cytokeratin-7, cofilin-2, transgelin-2, Hsp60, Hsc70, proteasome β-subunits (type-2 and type-3), nucleoside diphosphate kinase A, and cytosolic 5'(3')-deoxyribonucleotidase. 26640786 1 39 theme potential 271:279 arg1 impact 281:286 potential impact 271:286 potential impact in peritoneal dialysis 271:309 INTRODUCTION Senescence of peritoneal mesothelial cells represents a biological program defined by arrested cell growth and altered cell secretory phenotype with potential impact in peritoneal dialysis. 26640786 1 40 with phenotype 256:264 arg1 impact 281:286 potential impact 271:286 potential impact in peritoneal dialysis 271:309 INTRODUCTION Senescence of peritoneal mesothelial cells represents a biological program defined by arrested cell growth and altered cell secretory phenotype with potential impact in peritoneal dialysis. 26640786 8 41 theme cellular 1713:1720 arg1 response 1729:1736 cellular stress response 1713:1736 cellular stress response in peritoneal dialysis 1713:1759 Whereas changes in cytoskeleton-associated proteins likely reflect altered cell morphology, changes in chaperoning and housekeeping proteins may have functional impact on cellular stress response in peritoneal dialysis. 26640786 6 42 theme senescent 1349:1357 arg1 cells 1359:1363 senescent cells 1349:1363 senescent cells 1349:1363 Although the global level of O-GlcNAcylation was comparable, senescent cells were not sensitive to modulation by PUGNAc. 26640786 2 43 theme expression 395:404 arg1 profiles 406:413 global protein expression profiles 380:413 global protein expression profiles 380:413 This study aims to characterize cellular senescence at the level of global protein expression profiles and modification of proteins with O-linked N-acetylglucosamine (O-GlcNAcylation). 26640786 5 44 dep RESULTS 934:940 arg1 revealed 1000:1007 revealed 1000:1007 revealed 29 differentially abundant protein spots, 11 of which were identified to be actin (cytoplasmic 1 and 2), cytokeratin-7, cofilin-2, transgelin-2, Hsp60, Hsc70, proteasome β-subunits (type-2 and type-3), nucleoside diphosphate kinase A, and cytosolic 5'(3')-deoxyribonucleotidase 1000:1285 RESULTS Comparison of protein pattern of senescent and young HPMC revealed 29 differentially abundant protein spots, 11 of which were identified to be actin (cytoplasmic 1 and 2), cytokeratin-7, cofilin-2, transgelin-2, Hsp60, Hsc70, proteasome β-subunits (type-2 and type-3), nucleoside diphosphate kinase A, and cytosolic 5'(3')-deoxyribonucleotidase. 26640786 8 45 theme peritoneal 1741:1750 arg1 dialysis 1752:1759 peritoneal dialysis 1741:1759 peritoneal dialysis 1741:1759 Whereas changes in cytoskeleton-associated proteins likely reflect altered cell morphology, changes in chaperoning and housekeeping proteins may have functional impact on cellular stress response in peritoneal dialysis. 26640786 6 46 theme O-GlcNAcylation 1317:1331 arg1 comparable 1337:1346 comparable 1337:1346 comparable 1337:1346 Although the global level of O-GlcNAcylation was comparable, senescent cells were not sensitive to modulation by PUGNAc. 26640786 6 46 theme O-GlcNAcylation 1317:1331 arg1 level 1308:1312 the global level 1297:1312 the global level of O-GlcNAcylation 1297:1331 Although the global level of O-GlcNAcylation was comparable, senescent cells were not sensitive to modulation by PUGNAc. 26640786 1 47 theme cell 217:220 arg1 growth 222:227 arrested cell growth 208:227 arrested cell growth 208:227 INTRODUCTION Senescence of peritoneal mesothelial cells represents a biological program defined by arrested cell growth and altered cell secretory phenotype with potential impact in peritoneal dialysis. 26640786 7 48 theme senescent 1513:1521 arg1 cells 1535:1539 senescent mesothelial cells 1513:1539 senescent mesothelial cells 1513:1539 DISCUSSION This study identified changes of the proteome and altered dynamics of O-GlcNAc regulation in senescent mesothelial cells. 26640786 7 49 theme O-GlcNAc 1490:1497 arg1 regulation 1499:1508 O-GlcNAc regulation 1490:1508 O-GlcNAc regulation 1490:1508 DISCUSSION This study identified changes of the proteome and altered dynamics of O-GlcNAc regulation in senescent mesothelial cells. 26640786 5 50 dep β-subunits 1179:1188 arg1 type-2 1191:1196 type-2 1191:1196 type-2 1191:1196 RESULTS Comparison of protein pattern of senescent and young HPMC revealed 29 differentially abundant protein spots, 11 of which were identified to be actin (cytoplasmic 1 and 2), cytokeratin-7, cofilin-2, transgelin-2, Hsp60, Hsc70, proteasome β-subunits (type-2 and type-3), nucleoside diphosphate kinase A, and cytosolic 5'(3')-deoxyribonucleotidase. 26640786 5 50 dep β-subunits 1179:1188 arg1 type-3 1202:1207 type-3 1202:1207 type-3 1202:1207 RESULTS Comparison of protein pattern of senescent and young HPMC revealed 29 differentially abundant protein spots, 11 of which were identified to be actin (cytoplasmic 1 and 2), cytokeratin-7, cofilin-2, transgelin-2, Hsp60, Hsc70, proteasome β-subunits (type-2 and type-3), nucleoside diphosphate kinase A, and cytosolic 5'(3')-deoxyribonucleotidase. 26640786 3 51 theme gel 645:647 arg1 electrophoresis 649:663 two-dimensional gel electrophoresis 629:663 two-dimensional gel electrophoresis 629:663 METHODS A comparative proteomics analysis between young and senescent human peritoneal mesothelial cells (HPMC) was performed using two-dimensional gel electrophoresis. 26640786 5 52 theme HPMC 995:998 arg1 Comparison 942:951 Comparison 942:951 Comparison of protein pattern of senescent and young HPMC 942:998 RESULTS Comparison of protein pattern of senescent and young HPMC revealed 29 differentially abundant protein spots, 11 of which were identified to be actin (cytoplasmic 1 and 2), cytokeratin-7, cofilin-2, transgelin-2, Hsp60, Hsc70, proteasome β-subunits (type-2 and type-3), nucleoside diphosphate kinase A, and cytosolic 5'(3')-deoxyribonucleotidase. 26640786 8 53 theme altered 1609:1615 arg1 morphology 1622:1631 altered cell morphology 1609:1631 altered cell morphology 1609:1631 Whereas changes in cytoskeleton-associated proteins likely reflect altered cell morphology, changes in chaperoning and housekeeping proteins may have functional impact on cellular stress response in peritoneal dialysis. 26640786 7 54 theme dynamics 1478:1485 arg1 changes 1442:1448 changes 1442:1448 changes of the proteome and altered dynamics of O-GlcNAc regulation in senescent mesothelial cells 1442:1539 DISCUSSION This study identified changes of the proteome and altered dynamics of O-GlcNAc regulation in senescent mesothelial cells. 26640786 2 55 theme cellular 344:351 arg1 senescence 353:362 cellular senescence 344:362 cellular senescence 344:362 This study aims to characterize cellular senescence at the level of global protein expression profiles and modification of proteins with O-linked N-acetylglucosamine (O-GlcNAcylation). 26640786 5 56 theme protein 956:962 arg1 pattern 964:970 protein pattern 956:970 protein pattern 956:970 RESULTS Comparison of protein pattern of senescent and young HPMC revealed 29 differentially abundant protein spots, 11 of which were identified to be actin (cytoplasmic 1 and 2), cytokeratin-7, cofilin-2, transgelin-2, Hsp60, Hsc70, proteasome β-subunits (type-2 and type-3), nucleoside diphosphate kinase A, and cytosolic 5'(3')-deoxyribonucleotidase. 26640786 1 57 theme cell 241:244 arg1 phenotype 256:264 altered cell secretory phenotype 233:264 altered cell secretory phenotype 233:264 INTRODUCTION Senescence of peritoneal mesothelial cells represents a biological program defined by arrested cell growth and altered cell secretory phenotype with potential impact in peritoneal dialysis. 26640786 8 58 contain have 1687:1690 arg2 impact 1703:1708 functional impact 1692:1708 functional impact 1692:1708 Whereas changes in cytoskeleton-associated proteins likely reflect altered cell morphology, changes in chaperoning and housekeeping proteins may have functional impact on cellular stress response in peritoneal dialysis. 26640786 8 58 contain have 1687:1690 arg1 changes 1634:1640 changes 1634:1640 changes in chaperoning and housekeeping proteins 1634:1681 Whereas changes in cytoskeleton-associated proteins likely reflect altered cell morphology, changes in chaperoning and housekeeping proteins may have functional impact on cellular stress response in peritoneal dialysis. 26640786 5 59 theme proteasome 1168:1177 arg1 actin 1085:1089 actin 1085:1089 actin (cytoplasmic 1 and 2) 1085:1111 RESULTS Comparison of protein pattern of senescent and young HPMC revealed 29 differentially abundant protein spots, 11 of which were identified to be actin (cytoplasmic 1 and 2), cytokeratin-7, cofilin-2, transgelin-2, Hsp60, Hsc70, proteasome β-subunits (type-2 and type-3), nucleoside diphosphate kinase A, and cytosolic 5'(3')-deoxyribonucleotidase. 26640786 5 59 theme proteasome 1168:1177 arg1 β-subunits 1179:1188 proteasome β-subunits 1168:1188 proteasome β-subunits (type-2 and type-3) 1168:1208 RESULTS Comparison of protein pattern of senescent and young HPMC revealed 29 differentially abundant protein spots, 11 of which were identified to be actin (cytoplasmic 1 and 2), cytokeratin-7, cofilin-2, transgelin-2, Hsp60, Hsc70, proteasome β-subunits (type-2 and type-3), nucleoside diphosphate kinase A, and cytosolic 5'(3')-deoxyribonucleotidase. 26640786 1 60 theme peritoneal 136:145 arg1 cells 159:163 peritoneal mesothelial cells 136:163 peritoneal mesothelial cells 136:163 INTRODUCTION Senescence of peritoneal mesothelial cells represents a biological program defined by arrested cell growth and altered cell secretory phenotype with potential impact in peritoneal dialysis. 26640786 1 61 theme cells 159:163 arg1 Senescence 122:131 INTRODUCTION Senescence 109:131 INTRODUCTION Senescence of peritoneal mesothelial cells 109:163 INTRODUCTION Senescence of peritoneal mesothelial cells represents a biological program defined by arrested cell growth and altered cell secretory phenotype with potential impact in peritoneal dialysis. 26640786 8 62 theme cytoskeleton-associated 1561:1583 arg1 proteins 1585:1592 cytoskeleton-associated proteins 1561:1592 cytoskeleton-associated proteins 1561:1592 Whereas changes in cytoskeleton-associated proteins likely reflect altered cell morphology, changes in chaperoning and housekeeping proteins may have functional impact on cellular stress response in peritoneal dialysis. 26640786 0 63 theme Peritoneal 79:88 arg1 Cells 102:106 Human Peritoneal Mesothelial Cells 73:106 Human Peritoneal Mesothelial Cells 73:106 Senescence-Associated Changes in Proteome and O-GlcNAcylation Pattern in Human Peritoneal Mesothelial Cells. 26640786 7 64 dep proteome 1457:1464 arg1 the 1453:1455 the 1453:1455 the 1453:1455 DISCUSSION This study identified changes of the proteome and altered dynamics of O-GlcNAc regulation in senescent mesothelial cells. 26640786 5 65 theme abundant 1027:1034 arg1 spots 1044:1048 29 differentially abundant protein spots 1009:1048 29 differentially abundant protein spots 1009:1048 RESULTS Comparison of protein pattern of senescent and young HPMC revealed 29 differentially abundant protein spots, 11 of which were identified to be actin (cytoplasmic 1 and 2), cytokeratin-7, cofilin-2, transgelin-2, Hsp60, Hsc70, proteasome β-subunits (type-2 and type-3), nucleoside diphosphate kinase A, and cytosolic 5'(3')-deoxyribonucleotidase. 26640786 0 66 from Changes 22:28 arg1 O-GlcNAcylation 46:60 O-GlcNAcylation 46:60 O-GlcNAcylation 46:60 Senescence-Associated Changes in Proteome and O-GlcNAcylation Pattern in Human Peritoneal Mesothelial Cells. 26640786 0 66 from Changes 22:28 arg1 Proteome 33:40 Proteome 33:40 Proteome 33:40 Senescence-Associated Changes in Proteome and O-GlcNAcylation Pattern in Human Peritoneal Mesothelial Cells. 26640786 0 66 from Changes 22:28 arg1 Cells 102:106 Human Peritoneal Mesothelial Cells 73:106 Human Peritoneal Mesothelial Cells 73:106 Senescence-Associated Changes in Proteome and O-GlcNAcylation Pattern in Human Peritoneal Mesothelial Cells. 26640786 5 67 theme nucleoside 1211:1220 arg1 A 1241:1241 nucleoside diphosphate kinase A 1211:1241 nucleoside diphosphate kinase A 1211:1241 RESULTS Comparison of protein pattern of senescent and young HPMC revealed 29 differentially abundant protein spots, 11 of which were identified to be actin (cytoplasmic 1 and 2), cytokeratin-7, cofilin-2, transgelin-2, Hsp60, Hsc70, proteasome β-subunits (type-2 and type-3), nucleoside diphosphate kinase A, and cytosolic 5'(3')-deoxyribonucleotidase. 26640786 5 67 theme nucleoside 1211:1220 arg1 actin 1085:1089 actin 1085:1089 actin (cytoplasmic 1 and 2) 1085:1111 RESULTS Comparison of protein pattern of senescent and young HPMC revealed 29 differentially abundant protein spots, 11 of which were identified to be actin (cytoplasmic 1 and 2), cytokeratin-7, cofilin-2, transgelin-2, Hsp60, Hsc70, proteasome β-subunits (type-2 and type-3), nucleoside diphosphate kinase A, and cytosolic 5'(3')-deoxyribonucleotidase. 26640786 4 68 theme N-phenyl 877:884 arg1 carbamate 886:894 O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate 825:894 O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc) 825:903 O-GlcNAc status was assessed by Western blot under normal conditions and after modulation with 6-diazo-5-oxo-L-norleucine (DON) to decrease O-GlcNAcylation or O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc) to increase O-GlcNAcylation. 26640786 4 68 theme N-phenyl 877:884 arg1 PUGNAc 897:902 PUGNAc 897:902 PUGNAc 897:902 O-GlcNAc status was assessed by Western blot under normal conditions and after modulation with 6-diazo-5-oxo-L-norleucine (DON) to decrease O-GlcNAcylation or O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc) to increase O-GlcNAcylation. 26640786 8 69 from changes 1550:1556 arg1 proteins 1585:1592 cytoskeleton-associated proteins 1561:1592 cytoskeleton-associated proteins 1561:1592 Whereas changes in cytoskeleton-associated proteins likely reflect altered cell morphology, changes in chaperoning and housekeeping proteins may have functional impact on cellular stress response in peritoneal dialysis. 26640786 1 70 theme altered 233:239 arg1 phenotype 256:264 altered cell secretory phenotype 233:264 altered cell secretory phenotype 233:264 INTRODUCTION Senescence of peritoneal mesothelial cells represents a biological program defined by arrested cell growth and altered cell secretory phenotype with potential impact in peritoneal dialysis. 26640786 3 71 dep senescent 557:565 arg1 HPMC 603:606 HPMC 603:606 HPMC 603:606 METHODS A comparative proteomics analysis between young and senescent human peritoneal mesothelial cells (HPMC) was performed using two-dimensional gel electrophoresis. 26640786 3 71 dep senescent 557:565 arg1 cells 596:600 human peritoneal mesothelial cells 567:600 human peritoneal mesothelial cells (HPMC) 567:607 METHODS A comparative proteomics analysis between young and senescent human peritoneal mesothelial cells (HPMC) was performed using two-dimensional gel electrophoresis. 26640786 2 72 theme proteins 435:442 arg1 modification 419:430 modification 419:430 modification of proteins with O-linked N-acetylglucosamine (O-GlcNAcylation) 419:494 This study aims to characterize cellular senescence at the level of global protein expression profiles and modification of proteins with O-linked N-acetylglucosamine (O-GlcNAcylation). 26640786 2 72 theme proteins 435:442 arg1 profiles 406:413 global protein expression profiles 380:413 global protein expression profiles 380:413 This study aims to characterize cellular senescence at the level of global protein expression profiles and modification of proteins with O-linked N-acetylglucosamine (O-GlcNAcylation). 26640786 2 73 theme modification 419:430 arg1 level 371:375 the level 367:375 the level of global protein expression profiles and modification of proteins with O-linked N-acetylglucosamine (O-GlcNAcylation) 367:494 This study aims to characterize cellular senescence at the level of global protein expression profiles and modification of proteins with O-linked N-acetylglucosamine (O-GlcNAcylation). 26640786 5 74 theme cytosolic 1248:1256 arg1 actin 1085:1089 actin 1085:1089 actin (cytoplasmic 1 and 2) 1085:1111 RESULTS Comparison of protein pattern of senescent and young HPMC revealed 29 differentially abundant protein spots, 11 of which were identified to be actin (cytoplasmic 1 and 2), cytokeratin-7, cofilin-2, transgelin-2, Hsp60, Hsc70, proteasome β-subunits (type-2 and type-3), nucleoside diphosphate kinase A, and cytosolic 5'(3')-deoxyribonucleotidase. 26640786 5 74 theme cytosolic 1248:1256 arg1 -deoxyribonucleotidase 1264:1285 cytosolic 5'(3')-deoxyribonucleotidase 1248:1285 cytosolic 5'(3')-deoxyribonucleotidase 1248:1285 RESULTS Comparison of protein pattern of senescent and young HPMC revealed 29 differentially abundant protein spots, 11 of which were identified to be actin (cytoplasmic 1 and 2), cytokeratin-7, cofilin-2, transgelin-2, Hsp60, Hsc70, proteasome β-subunits (type-2 and type-3), nucleoside diphosphate kinase A, and cytosolic 5'(3')-deoxyribonucleotidase. 26640786 7 75 from changes 1442:1448 arg1 cells 1535:1539 senescent mesothelial cells 1513:1539 senescent mesothelial cells 1513:1539 DISCUSSION This study identified changes of the proteome and altered dynamics of O-GlcNAc regulation in senescent mesothelial cells. 26640786 8 76 theme housekeeping 1661:1672 arg1 proteins 1674:1681 housekeeping proteins 1661:1681 housekeeping proteins 1661:1681 Whereas changes in cytoskeleton-associated proteins likely reflect altered cell morphology, changes in chaperoning and housekeeping proteins may have functional impact on cellular stress response in peritoneal dialysis. 26640786 8 77 from changes 1634:1640 arg1 chaperoning 1645:1655 chaperoning 1645:1655 chaperoning 1645:1655 Whereas changes in cytoskeleton-associated proteins likely reflect altered cell morphology, changes in chaperoning and housekeeping proteins may have functional impact on cellular stress response in peritoneal dialysis. 26640786 8 77 from changes 1634:1640 arg1 proteins 1674:1681 housekeeping proteins 1661:1681 housekeeping proteins 1661:1681 Whereas changes in cytoskeleton-associated proteins likely reflect altered cell morphology, changes in chaperoning and housekeeping proteins may have functional impact on cellular stress response in peritoneal dialysis. 26640786 4 78 with modulation 745:754 arg1 DON 789:791 DON 789:791 DON 789:791 O-GlcNAc status was assessed by Western blot under normal conditions and after modulation with 6-diazo-5-oxo-L-norleucine (DON) to decrease O-GlcNAcylation or O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc) to increase O-GlcNAcylation. 26640786 4 78 with modulation 745:754 arg1 6-diazo-5-oxo-L-norleucine 761:786 6-diazo-5-oxo-L-norleucine 761:786 6-diazo-5-oxo-L-norleucine (DON) 761:792 O-GlcNAc status was assessed by Western blot under normal conditions and after modulation with 6-diazo-5-oxo-L-norleucine (DON) to decrease O-GlcNAcylation or O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc) to increase O-GlcNAcylation. 26640786 3 79 theme proteomics 519:528 arg1 analysis 530:537 A comparative proteomics analysis 505:537 METHODS A comparative proteomics analysis between young and senescent human peritoneal mesothelial cells (HPMC) 497:607 METHODS A comparative proteomics analysis between young and senescent human peritoneal mesothelial cells (HPMC) was performed using two-dimensional gel electrophoresis. 26640786 5 80 theme kinase 1234:1239 arg1 A 1241:1241 nucleoside diphosphate kinase A 1211:1241 nucleoside diphosphate kinase A 1211:1241 RESULTS Comparison of protein pattern of senescent and young HPMC revealed 29 differentially abundant protein spots, 11 of which were identified to be actin (cytoplasmic 1 and 2), cytokeratin-7, cofilin-2, transgelin-2, Hsp60, Hsc70, proteasome β-subunits (type-2 and type-3), nucleoside diphosphate kinase A, and cytosolic 5'(3')-deoxyribonucleotidase. 26640786 5 80 theme kinase 1234:1239 arg1 actin 1085:1089 actin 1085:1089 actin (cytoplasmic 1 and 2) 1085:1111 RESULTS Comparison of protein pattern of senescent and young HPMC revealed 29 differentially abundant protein spots, 11 of which were identified to be actin (cytoplasmic 1 and 2), cytokeratin-7, cofilin-2, transgelin-2, Hsp60, Hsc70, proteasome β-subunits (type-2 and type-3), nucleoside diphosphate kinase A, and cytosolic 5'(3')-deoxyribonucleotidase. 26640786 3 81 dep METHODS 497:503 arg1 analysis 530:537 A comparative proteomics analysis 505:537 METHODS A comparative proteomics analysis between young and senescent human peritoneal mesothelial cells (HPMC) 497:607 METHODS A comparative proteomics analysis between young and senescent human peritoneal mesothelial cells (HPMC) was performed using two-dimensional gel electrophoresis. 26640786 8 82 theme functional 1692:1701 arg1 impact 1703:1708 functional impact 1692:1708 functional impact 1692:1708 Whereas changes in cytoskeleton-associated proteins likely reflect altered cell morphology, changes in chaperoning and housekeeping proteins may have functional impact on cellular stress response in peritoneal dialysis. 26640786 3 83 theme mesothelial 584:594 arg1 HPMC 603:606 HPMC 603:606 HPMC 603:606 METHODS A comparative proteomics analysis between young and senescent human peritoneal mesothelial cells (HPMC) was performed using two-dimensional gel electrophoresis. 26640786 3 83 theme mesothelial 584:594 arg1 cells 596:600 human peritoneal mesothelial cells 567:600 human peritoneal mesothelial cells (HPMC) 567:607 METHODS A comparative proteomics analysis between young and senescent human peritoneal mesothelial cells (HPMC) was performed using two-dimensional gel electrophoresis. 26640786 3 84 theme human 567:571 arg1 HPMC 603:606 HPMC 603:606 HPMC 603:606 METHODS A comparative proteomics analysis between young and senescent human peritoneal mesothelial cells (HPMC) was performed using two-dimensional gel electrophoresis. 26640786 3 84 theme human 567:571 arg1 cells 596:600 human peritoneal mesothelial cells 567:600 human peritoneal mesothelial cells (HPMC) 567:607 METHODS A comparative proteomics analysis between young and senescent human peritoneal mesothelial cells (HPMC) was performed using two-dimensional gel electrophoresis. 26640786 0 85 dep Proteome 33:40 arg1 Pattern 62:68 Pattern 62:68 Pattern 62:68 Senescence-Associated Changes in Proteome and O-GlcNAcylation Pattern in Human Peritoneal Mesothelial Cells. 26640786 2 86 with profiles 406:413 arg1 N-acetylglucosamine 458:476 O-linked N-acetylglucosamine 449:476 O-linked N-acetylglucosamine (O-GlcNAcylation) 449:494 This study aims to characterize cellular senescence at the level of global protein expression profiles and modification of proteins with O-linked N-acetylglucosamine (O-GlcNAcylation). 26640786 2 86 with profiles 406:413 arg1 O-GlcNAcylation 479:493 O-GlcNAcylation 479:493 O-GlcNAcylation 479:493 This study aims to characterize cellular senescence at the level of global protein expression profiles and modification of proteins with O-linked N-acetylglucosamine (O-GlcNAcylation). 26640786 8 87 theme stress 1722:1727 arg1 response 1729:1736 cellular stress response 1713:1736 cellular stress response in peritoneal dialysis 1713:1759 Whereas changes in cytoskeleton-associated proteins likely reflect altered cell morphology, changes in chaperoning and housekeeping proteins may have functional impact on cellular stress response in peritoneal dialysis. 26640786 4 88 theme Western 698:704 arg1 blot 706:709 Western blot 698:709 Western blot 698:709 O-GlcNAc status was assessed by Western blot under normal conditions and after modulation with 6-diazo-5-oxo-L-norleucine (DON) to decrease O-GlcNAcylation or O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc) to increase O-GlcNAcylation. 26640786 2 89 theme profiles 406:413 arg1 level 371:375 the level 367:375 the level of global protein expression profiles and modification of proteins with O-linked N-acetylglucosamine (O-GlcNAcylation) 367:494 This study aims to characterize cellular senescence at the level of global protein expression profiles and modification of proteins with O-linked N-acetylglucosamine (O-GlcNAcylation). 26304035 9 0 theme chitin 1642:1647 arg1 deacetylase 1649:1659 chitin deacetylase 1642:1659 chitin deacetylase 1642:1659 A better understanding of chitin metabolism in the hemimetabolous insect, N. lugens, would be achieved by considering three chitinolytic enzyme families: chitinase, chitin deacetylase and β-N-acetylhexosaminidase. 26304035 9 0 theme chitin 1642:1647 arg1 families 1621:1628 three chitinolytic enzyme families 1595:1628 three chitinolytic enzyme families: chitinase, chitin deacetylase and β-N-acetylhexosaminidase 1595:1688 A better understanding of chitin metabolism in the hemimetabolous insect, N. lugens, would be achieved by considering three chitinolytic enzyme families: chitinase, chitin deacetylase and β-N-acetylhexosaminidase. 26304035 1 1 theme chitin 153:158 arg1 oligosaccharides 160:175 the chitin oligosaccharides 149:175 the chitin oligosaccharides that are produced by the activity of chitinases on chitin in insects 149:244 β-N-Acetylhexosaminidases (HEXs) are enzymes that can degrade the chitin oligosaccharides that are produced by the activity of chitinases on chitin in insects. 26304035 7 2 theme other 1248:1252 arg1 NlHexs 1257:1262 the other 10 NlHexs 1244:1262 the other 10 NlHexs 1244:1262 RNA interference (RNAi) demonstrated failure to shed the old cuticle only in the nymphs treated with double-stranded RNA (dsRNA) targeting NlHex4, and these nymphs eventually died; no observable morphological abnormalities were found in insects treated with dsRNAs targeting the other 10 NlHexs. 26304035 5 3 theme different 684:692 arg1 stages 708:713 different developmental stages 684:713 different developmental stages 684:713 Observations of the expression of NlHexs during different developmental stages revealed that NlHex4 is expressed with periodicity during moulting. 26304035 2 4 from genes 348:352 arg1 lugens 378:383 Nilaparvata lugens 366:383 Nilaparvata lugens 366:383 Using bioinformatic methods based on genome and transcriptome databases, 11 β-N-acetylhexosaminidase genes (NlHexs) in Nilaparvata lugens were identified and characterized. 26304035 2 5 dep genome 284:289 arg1 databases 309:317 databases 309:317 databases 309:317 Using bioinformatic methods based on genome and transcriptome databases, 11 β-N-acetylhexosaminidase genes (NlHexs) in Nilaparvata lugens were identified and characterized. 26304035 9 6 from insect 1543:1548 arg1 understanding 1486:1498 A better understanding 1477:1498 A better understanding of chitin metabolism in the hemimetabolous insect, N. lugens, 1477:1560 A better understanding of chitin metabolism in the hemimetabolous insect, N. lugens, would be achieved by considering three chitinolytic enzyme families: chitinase, chitin deacetylase and β-N-acetylhexosaminidase. 26304035 5 7 theme developmental 694:706 arg1 stages 708:713 different developmental stages 684:713 different developmental stages 684:713 Observations of the expression of NlHexs during different developmental stages revealed that NlHex4 is expressed with periodicity during moulting. 26304035 8 8 theme enzymes 1350:1356 arg1 pattern 1326:1332 a '5 + 1 + 3' pattern 1312:1332 a '5 + 1 + 3' pattern of chitinolytic enzymes 1312:1356 Based on this study and our previous analyses, a '5 + 1 + 3' pattern of chitinolytic enzymes is proposed, in which five chitinases, one NlHEX and three chitin deacetylases are required for moulting in N. lugens. 26304035 7 9 theme RNA 969:971 arg1 RNAi 987:990 RNAi 987:990 RNAi 987:990 RNA interference (RNAi) demonstrated failure to shed the old cuticle only in the nymphs treated with double-stranded RNA (dsRNA) targeting NlHex4, and these nymphs eventually died; no observable morphological abnormalities were found in insects treated with dsRNAs targeting the other 10 NlHexs. 26304035 7 9 theme RNA 969:971 arg1 interference 973:984 RNA interference 969:984 RNA interference (RNAi) 969:991 RNA interference (RNAi) demonstrated failure to shed the old cuticle only in the nymphs treated with double-stranded RNA (dsRNA) targeting NlHex4, and these nymphs eventually died; no observable morphological abnormalities were found in insects treated with dsRNAs targeting the other 10 NlHexs. 26304035 4 10 theme O-GlcNAcase 518:528 arg1 group 531:535 The O-Linked N-acetylglucosaminidase (O-GlcNAcase) group 480:535 The O-Linked N-acetylglucosaminidase (O-GlcNAcase) group 480:535 The O-Linked N-acetylglucosaminidase (O-GlcNAcase) group includes NlHex11, which harbours a catalytic domain that differs from that of the other 10 NlHexs. 26304035 9 11 from metabolism 1510:1519 arg1 N. lugens 1551:1559 N. lugens 1551:1559 N. lugens 1551:1559 A better understanding of chitin metabolism in the hemimetabolous insect, N. lugens, would be achieved by considering three chitinolytic enzyme families: chitinase, chitin deacetylase and β-N-acetylhexosaminidase. 26304035 9 11 from metabolism 1510:1519 arg1 insect 1543:1548 the hemimetabolous insect 1524:1548 the hemimetabolous insect 1524:1548 A better understanding of chitin metabolism in the hemimetabolous insect, N. lugens, would be achieved by considering three chitinolytic enzyme families: chitinase, chitin deacetylase and β-N-acetylhexosaminidase. 26304035 8 12 theme chitinolytic 1337:1348 arg1 enzymes 1350:1356 chitinolytic enzymes 1337:1356 chitinolytic enzymes 1337:1356 Based on this study and our previous analyses, a '5 + 1 + 3' pattern of chitinolytic enzymes is proposed, in which five chitinases, one NlHEX and three chitin deacetylases are required for moulting in N. lugens. 26304035 4 13 theme other 619:623 arg1 NlHexs 628:633 the other 10 NlHexs 615:633 the other 10 NlHexs 615:633 The O-Linked N-acetylglucosaminidase (O-GlcNAcase) group includes NlHex11, which harbours a catalytic domain that differs from that of the other 10 NlHexs. 26304035 9 14 theme better 1479:1484 arg1 understanding 1486:1498 A better understanding 1477:1498 A better understanding of chitin metabolism in the hemimetabolous insect, N. lugens, 1477:1560 A better understanding of chitin metabolism in the hemimetabolous insect, N. lugens, would be achieved by considering three chitinolytic enzyme families: chitinase, chitin deacetylase and β-N-acetylhexosaminidase. 26304035 6 15 theme tissue-specific 796:810 arg1 nonspecific 852:862 nonspecific 852:862 nonspecific 852:862 Although the tissue-specific expression patterns of most NlHexs were nonspecific, NlHex4 was found to be expressed mainly in the female reproductive system as well as in the integument. 26304035 6 15 theme tissue-specific 796:810 arg1 patterns 823:830 the tissue-specific expression patterns 792:830 the tissue-specific expression patterns of most NlHexs 792:845 Although the tissue-specific expression patterns of most NlHexs were nonspecific, NlHex4 was found to be expressed mainly in the female reproductive system as well as in the integument. 26304035 3 16 theme tree 465:468 arg1 topology 470:477 a six-grouped tree topology 451:477 a six-grouped tree topology 451:477 Phylogenetic analysis revealed a six-grouped tree topology. 26304035 7 17 theme observable 1153:1162 arg1 abnormalities 1178:1190 no observable morphological abnormalities 1150:1190 no observable morphological abnormalities 1150:1190 RNA interference (RNAi) demonstrated failure to shed the old cuticle only in the nymphs treated with double-stranded RNA (dsRNA) targeting NlHex4, and these nymphs eventually died; no observable morphological abnormalities were found in insects treated with dsRNAs targeting the other 10 NlHexs. 26304035 5 18 theme expression 656:665 arg1 Observations 636:647 Observations 636:647 Observations of the expression of NlHexs during different developmental stages 636:713 Observations of the expression of NlHexs during different developmental stages revealed that NlHex4 is expressed with periodicity during moulting. 26304035 0 19 theme β-N-acetylhexosaminidase 4:27 arg1 family 34:39 The β-N-acetylhexosaminidase gene family 0:39 The β-N-acetylhexosaminidase gene family in the brown 0:52 The β-N-acetylhexosaminidase gene family in the brown planthopper, Nilaparvata lugens. 26304035 9 20 from understanding 1486:1498 arg1 N. lugens 1551:1559 N. lugens 1551:1559 N. lugens 1551:1559 A better understanding of chitin metabolism in the hemimetabolous insect, N. lugens, would be achieved by considering three chitinolytic enzyme families: chitinase, chitin deacetylase and β-N-acetylhexosaminidase. 26304035 9 20 from understanding 1486:1498 arg1 insect 1543:1548 the hemimetabolous insect 1524:1548 the hemimetabolous insect 1524:1548 A better understanding of chitin metabolism in the hemimetabolous insect, N. lugens, would be achieved by considering three chitinolytic enzyme families: chitinase, chitin deacetylase and β-N-acetylhexosaminidase. 26304035 5 21 theme NlHexs 670:675 arg1 expression 656:665 the expression 652:665 the expression of NlHexs during different developmental stages 652:713 Observations of the expression of NlHexs during different developmental stages revealed that NlHex4 is expressed with periodicity during moulting. 26304035 6 22 theme NlHexs 840:845 arg1 nonspecific 852:862 nonspecific 852:862 nonspecific 852:862 Although the tissue-specific expression patterns of most NlHexs were nonspecific, NlHex4 was found to be expressed mainly in the female reproductive system as well as in the integument. 26304035 6 22 theme NlHexs 840:845 arg1 patterns 823:830 the tissue-specific expression patterns 792:830 the tissue-specific expression patterns of most NlHexs 792:845 Although the tissue-specific expression patterns of most NlHexs were nonspecific, NlHex4 was found to be expressed mainly in the female reproductive system as well as in the integument. 26304035 0 23 dep lugens 79:84 arg1 family 34:39 The β-N-acetylhexosaminidase gene family 0:39 The β-N-acetylhexosaminidase gene family in the brown 0:52 The β-N-acetylhexosaminidase gene family in the brown planthopper, Nilaparvata lugens. 26304035 3 24 theme six-grouped 453:463 arg1 topology 470:477 a six-grouped tree topology 451:477 a six-grouped tree topology 451:477 Phylogenetic analysis revealed a six-grouped tree topology. 26304035 7 25 located found 1197:1201 arg2 abnormalities 1178:1190 no observable morphological abnormalities 1150:1190 no observable morphological abnormalities 1150:1190 RNA interference (RNAi) demonstrated failure to shed the old cuticle only in the nymphs treated with double-stranded RNA (dsRNA) targeting NlHex4, and these nymphs eventually died; no observable morphological abnormalities were found in insects treated with dsRNAs targeting the other 10 NlHexs. 26304035 7 25 located found 1197:1201 arg1 insects 1206:1212 insects 1206:1212 insects treated with dsRNAs targeting the other 10 NlHexs 1206:1262 RNA interference (RNAi) demonstrated failure to shed the old cuticle only in the nymphs treated with double-stranded RNA (dsRNA) targeting NlHex4, and these nymphs eventually died; no observable morphological abnormalities were found in insects treated with dsRNAs targeting the other 10 NlHexs. 26304035 6 26 theme most 835:838 arg1 NlHexs 840:845 most NlHexs 835:845 most NlHexs 835:845 Although the tissue-specific expression patterns of most NlHexs were nonspecific, NlHex4 was found to be expressed mainly in the female reproductive system as well as in the integument. 26304035 0 27 theme gene 29:32 arg1 family 34:39 The β-N-acetylhexosaminidase gene family 0:39 The β-N-acetylhexosaminidase gene family in the brown 0:52 The β-N-acetylhexosaminidase gene family in the brown planthopper, Nilaparvata lugens. 26304035 9 28 dep families 1621:1628 arg1 β-N-acetylhexosaminidase 1665:1688 β-N-acetylhexosaminidase 1665:1688 β-N-acetylhexosaminidase 1665:1688 A better understanding of chitin metabolism in the hemimetabolous insect, N. lugens, would be achieved by considering three chitinolytic enzyme families: chitinase, chitin deacetylase and β-N-acetylhexosaminidase. 26304035 9 28 dep families 1621:1628 arg1 chitinase 1631:1639 chitinase 1631:1639 chitinase 1631:1639 A better understanding of chitin metabolism in the hemimetabolous insect, N. lugens, would be achieved by considering three chitinolytic enzyme families: chitinase, chitin deacetylase and β-N-acetylhexosaminidase. 26304035 9 28 dep families 1621:1628 arg1 deacetylase 1649:1659 chitin deacetylase 1642:1659 chitin deacetylase 1642:1659 A better understanding of chitin metabolism in the hemimetabolous insect, N. lugens, would be achieved by considering three chitinolytic enzyme families: chitinase, chitin deacetylase and β-N-acetylhexosaminidase. 26304035 9 28 dep families 1621:1628 arg1 families 1621:1628 three chitinolytic enzyme families 1595:1628 three chitinolytic enzyme families: chitinase, chitin deacetylase and β-N-acetylhexosaminidase 1595:1688 A better understanding of chitin metabolism in the hemimetabolous insect, N. lugens, would be achieved by considering three chitinolytic enzyme families: chitinase, chitin deacetylase and β-N-acetylhexosaminidase. 26304035 6 29 theme reproductive 919:930 arg1 system 932:937 the female reproductive system 908:937 the female reproductive system 908:937 Although the tissue-specific expression patterns of most NlHexs were nonspecific, NlHex4 was found to be expressed mainly in the female reproductive system as well as in the integument. 26304035 9 30 theme hemimetabolous 1528:1541 arg1 N. lugens 1551:1559 N. lugens 1551:1559 N. lugens 1551:1559 A better understanding of chitin metabolism in the hemimetabolous insect, N. lugens, would be achieved by considering three chitinolytic enzyme families: chitinase, chitin deacetylase and β-N-acetylhexosaminidase. 26304035 9 30 theme hemimetabolous 1528:1541 arg1 insect 1543:1548 the hemimetabolous insect 1524:1548 the hemimetabolous insect 1524:1548 A better understanding of chitin metabolism in the hemimetabolous insect, N. lugens, would be achieved by considering three chitinolytic enzyme families: chitinase, chitin deacetylase and β-N-acetylhexosaminidase. 26304035 7 31 theme morphological 1164:1176 arg1 abnormalities 1178:1190 no observable morphological abnormalities 1150:1190 no observable morphological abnormalities 1150:1190 RNA interference (RNAi) demonstrated failure to shed the old cuticle only in the nymphs treated with double-stranded RNA (dsRNA) targeting NlHex4, and these nymphs eventually died; no observable morphological abnormalities were found in insects treated with dsRNAs targeting the other 10 NlHexs. 26304035 6 32 theme female 912:917 arg1 system 932:937 the female reproductive system 908:937 the female reproductive system 908:937 Although the tissue-specific expression patterns of most NlHexs were nonspecific, NlHex4 was found to be expressed mainly in the female reproductive system as well as in the integument. 26304035 8 33 theme previous 1293:1300 arg1 analyses 1302:1309 our previous analyses 1289:1309 our previous analyses 1289:1309 Based on this study and our previous analyses, a '5 + 1 + 3' pattern of chitinolytic enzymes is proposed, in which five chitinases, one NlHEX and three chitin deacetylases are required for moulting in N. lugens. 26304035 4 34 theme N-acetylglucosaminidase 493:515 arg1 group 531:535 The O-Linked N-acetylglucosaminidase (O-GlcNAcase) group 480:535 The O-Linked N-acetylglucosaminidase (O-GlcNAcase) group 480:535 The O-Linked N-acetylglucosaminidase (O-GlcNAcase) group includes NlHex11, which harbours a catalytic domain that differs from that of the other 10 NlHexs. 26304035 1 35 theme chitinases 214:223 arg1 activity 202:209 the activity 198:209 the activity of chitinases on chitin in insects 198:244 β-N-Acetylhexosaminidases (HEXs) are enzymes that can degrade the chitin oligosaccharides that are produced by the activity of chitinases on chitin in insects. 26304035 7 36 theme double-stranded 1070:1084 arg1 dsRNA 1091:1095 dsRNA 1091:1095 dsRNA 1091:1095 RNA interference (RNAi) demonstrated failure to shed the old cuticle only in the nymphs treated with double-stranded RNA (dsRNA) targeting NlHex4, and these nymphs eventually died; no observable morphological abnormalities were found in insects treated with dsRNAs targeting the other 10 NlHexs. 26304035 7 36 theme double-stranded 1070:1084 arg1 RNA 1086:1088 double-stranded RNA 1070:1088 double-stranded RNA (dsRNA) targeting NlHex4 1070:1113 RNA interference (RNAi) demonstrated failure to shed the old cuticle only in the nymphs treated with double-stranded RNA (dsRNA) targeting NlHex4, and these nymphs eventually died; no observable morphological abnormalities were found in insects treated with dsRNAs targeting the other 10 NlHexs. 26304035 4 37 theme O-Linked 484:491 arg1 group 531:535 The O-Linked N-acetylglucosaminidase (O-GlcNAcase) group 480:535 The O-Linked N-acetylglucosaminidase (O-GlcNAcase) group 480:535 The O-Linked N-acetylglucosaminidase (O-GlcNAcase) group includes NlHex11, which harbours a catalytic domain that differs from that of the other 10 NlHexs. 26304035 9 38 theme chitinolytic 1601:1612 arg1 β-N-acetylhexosaminidase 1665:1688 β-N-acetylhexosaminidase 1665:1688 β-N-acetylhexosaminidase 1665:1688 A better understanding of chitin metabolism in the hemimetabolous insect, N. lugens, would be achieved by considering three chitinolytic enzyme families: chitinase, chitin deacetylase and β-N-acetylhexosaminidase. 26304035 9 38 theme chitinolytic 1601:1612 arg1 chitinase 1631:1639 chitinase 1631:1639 chitinase 1631:1639 A better understanding of chitin metabolism in the hemimetabolous insect, N. lugens, would be achieved by considering three chitinolytic enzyme families: chitinase, chitin deacetylase and β-N-acetylhexosaminidase. 26304035 9 38 theme chitinolytic 1601:1612 arg1 deacetylase 1649:1659 chitin deacetylase 1642:1659 chitin deacetylase 1642:1659 A better understanding of chitin metabolism in the hemimetabolous insect, N. lugens, would be achieved by considering three chitinolytic enzyme families: chitinase, chitin deacetylase and β-N-acetylhexosaminidase. 26304035 9 38 theme chitinolytic 1601:1612 arg1 families 1621:1628 three chitinolytic enzyme families 1595:1628 three chitinolytic enzyme families: chitinase, chitin deacetylase and β-N-acetylhexosaminidase 1595:1688 A better understanding of chitin metabolism in the hemimetabolous insect, N. lugens, would be achieved by considering three chitinolytic enzyme families: chitinase, chitin deacetylase and β-N-acetylhexosaminidase. 26304035 1 39 from chitinases 214:223 arg1 chitin 228:233 chitin 228:233 chitin 228:233 β-N-Acetylhexosaminidases (HEXs) are enzymes that can degrade the chitin oligosaccharides that are produced by the activity of chitinases on chitin in insects. 26304035 8 40 theme 5 + 1 + 3 1315:1323 arg1 pattern 1326:1332 a '5 + 1 + 3' pattern 1312:1332 a '5 + 1 + 3' pattern of chitinolytic enzymes 1312:1356 Based on this study and our previous analyses, a '5 + 1 + 3' pattern of chitinolytic enzymes is proposed, in which five chitinases, one NlHEX and three chitin deacetylases are required for moulting in N. lugens. 26304035 3 41 theme Phylogenetic 420:431 arg1 analysis 433:440 Phylogenetic analysis 420:440 Phylogenetic analysis 420:440 Phylogenetic analysis revealed a six-grouped tree topology. 26304035 9 42 theme enzyme 1614:1619 arg1 β-N-acetylhexosaminidase 1665:1688 β-N-acetylhexosaminidase 1665:1688 β-N-acetylhexosaminidase 1665:1688 A better understanding of chitin metabolism in the hemimetabolous insect, N. lugens, would be achieved by considering three chitinolytic enzyme families: chitinase, chitin deacetylase and β-N-acetylhexosaminidase. 26304035 9 42 theme enzyme 1614:1619 arg1 chitinase 1631:1639 chitinase 1631:1639 chitinase 1631:1639 A better understanding of chitin metabolism in the hemimetabolous insect, N. lugens, would be achieved by considering three chitinolytic enzyme families: chitinase, chitin deacetylase and β-N-acetylhexosaminidase. 26304035 9 42 theme enzyme 1614:1619 arg1 deacetylase 1649:1659 chitin deacetylase 1642:1659 chitin deacetylase 1642:1659 A better understanding of chitin metabolism in the hemimetabolous insect, N. lugens, would be achieved by considering three chitinolytic enzyme families: chitinase, chitin deacetylase and β-N-acetylhexosaminidase. 26304035 9 42 theme enzyme 1614:1619 arg1 families 1621:1628 three chitinolytic enzyme families 1595:1628 three chitinolytic enzyme families: chitinase, chitin deacetylase and β-N-acetylhexosaminidase 1595:1688 A better understanding of chitin metabolism in the hemimetabolous insect, N. lugens, would be achieved by considering three chitinolytic enzyme families: chitinase, chitin deacetylase and β-N-acetylhexosaminidase. 26304035 6 43 theme expression 812:821 arg1 nonspecific 852:862 nonspecific 852:862 nonspecific 852:862 Although the tissue-specific expression patterns of most NlHexs were nonspecific, NlHex4 was found to be expressed mainly in the female reproductive system as well as in the integument. 26304035 6 43 theme expression 812:821 arg1 patterns 823:830 the tissue-specific expression patterns 792:830 the tissue-specific expression patterns of most NlHexs 792:845 Although the tissue-specific expression patterns of most NlHexs were nonspecific, NlHex4 was found to be expressed mainly in the female reproductive system as well as in the integument. 26304035 4 44 theme catalytic 572:580 arg1 domain 582:587 a catalytic domain 570:587 a catalytic domain that differs from that of the other 10 NlHexs 570:633 The O-Linked N-acetylglucosaminidase (O-GlcNAcase) group includes NlHex11, which harbours a catalytic domain that differs from that of the other 10 NlHexs. 26304035 1 45 from activity 202:209 arg1 insects 238:244 insects 238:244 insects 238:244 β-N-Acetylhexosaminidases (HEXs) are enzymes that can degrade the chitin oligosaccharides that are produced by the activity of chitinases on chitin in insects. 26304035 1 45 from activity 202:209 arg1 chitin 228:233 chitin 228:233 chitin 228:233 β-N-Acetylhexosaminidases (HEXs) are enzymes that can degrade the chitin oligosaccharides that are produced by the activity of chitinases on chitin in insects. 26304035 1 46 from chitin 228:233 arg1 activity 202:209 the activity 198:209 the activity of chitinases on chitin in insects 198:244 β-N-Acetylhexosaminidases (HEXs) are enzymes that can degrade the chitin oligosaccharides that are produced by the activity of chitinases on chitin in insects. 26304035 2 47 theme bioinformatic 253:265 arg1 methods 267:273 bioinformatic methods 253:273 bioinformatic methods based on genome and transcriptome databases 253:317 Using bioinformatic methods based on genome and transcriptome databases, 11 β-N-acetylhexosaminidase genes (NlHexs) in Nilaparvata lugens were identified and characterized. 26304035 7 48 theme old 1026:1028 arg1 cuticle 1030:1036 the old cuticle 1022:1036 the old cuticle 1022:1036 RNA interference (RNAi) demonstrated failure to shed the old cuticle only in the nymphs treated with double-stranded RNA (dsRNA) targeting NlHex4, and these nymphs eventually died; no observable morphological abnormalities were found in insects treated with dsRNAs targeting the other 10 NlHexs. 26304035 2 49 theme β-N-acetylhexosaminidase 323:346 arg1 NlHexs 355:360 NlHexs 355:360 NlHexs 355:360 Using bioinformatic methods based on genome and transcriptome databases, 11 β-N-acetylhexosaminidase genes (NlHexs) in Nilaparvata lugens were identified and characterized. 26304035 2 49 theme β-N-acetylhexosaminidase 323:346 arg1 genes 348:352 11 β-N-acetylhexosaminidase genes 320:352 11 β-N-acetylhexosaminidase genes (NlHexs) in Nilaparvata lugens 320:383 Using bioinformatic methods based on genome and transcriptome databases, 11 β-N-acetylhexosaminidase genes (NlHexs) in Nilaparvata lugens were identified and characterized. 26304035 8 50 from moulting 1454:1461 arg1 N. lugens 1466:1474 N. lugens 1466:1474 N. lugens 1466:1474 Based on this study and our previous analyses, a '5 + 1 + 3' pattern of chitinolytic enzymes is proposed, in which five chitinases, one NlHEX and three chitin deacetylases are required for moulting in N. lugens. 26304035 9 51 theme metabolism 1510:1519 arg1 understanding 1486:1498 A better understanding 1477:1498 A better understanding of chitin metabolism in the hemimetabolous insect, N. lugens, 1477:1560 A better understanding of chitin metabolism in the hemimetabolous insect, N. lugens, would be achieved by considering three chitinolytic enzyme families: chitinase, chitin deacetylase and β-N-acetylhexosaminidase. 26304035 9 52 theme chitin 1503:1508 arg1 metabolism 1510:1519 chitin metabolism 1503:1519 chitin metabolism in the hemimetabolous insect, N. lugens, 1503:1560 A better understanding of chitin metabolism in the hemimetabolous insect, N. lugens, would be achieved by considering three chitinolytic enzyme families: chitinase, chitin deacetylase and β-N-acetylhexosaminidase. 26304035 0 53 from family 34:39 arg1 brown 48:52 the brown 44:52 the brown 44:52 The β-N-acetylhexosaminidase gene family in the brown planthopper, Nilaparvata lugens. 26304035 8 54 theme chitin 1417:1422 arg1 chitinases 1385:1394 five chitinases 1380:1394 five chitinases 1380:1394 Based on this study and our previous analyses, a '5 + 1 + 3' pattern of chitinolytic enzymes is proposed, in which five chitinases, one NlHEX and three chitin deacetylases are required for moulting in N. lugens. 26304035 8 54 theme chitin 1417:1422 arg1 deacetylases 1424:1435 three chitin deacetylases 1411:1435 three chitin deacetylases 1411:1435 Based on this study and our previous analyses, a '5 + 1 + 3' pattern of chitinolytic enzymes is proposed, in which five chitinases, one NlHEX and three chitin deacetylases are required for moulting in N. lugens. 26304035 2 55 theme Nilaparvata 366:376 arg1 lugens 378:383 Nilaparvata lugens 366:383 Nilaparvata lugens 366:383 Using bioinformatic methods based on genome and transcriptome databases, 11 β-N-acetylhexosaminidase genes (NlHexs) in Nilaparvata lugens were identified and characterized. 26299246 5 0 theme C. 634:635 arg1 strains 646:652 The C. albicans strains 630:652 The C. albicans strains with controlled expression of DPM genes 630:692 The C. albicans strains with controlled expression of DPM genes were constructed and analyzed. 26299246 3 1 theme cell 482:485 arg1 wall 487:490 the cell wall composition and morphogenesis 478:520 wall 487:490 Here we describe the role of DPMS for Candida albicans physiology with emphasis on the cell wall composition and morphogenesis. 26299246 1 2 theme -anchor 245:251 arg1 synthesis 253:261 glycosylphosphatidylinositol (GPI)-anchor synthesis 211:261 glycosylphosphatidylinositol (GPI)-anchor synthesis 211:261 BACKGROUND Dolichol phosphate mannose synthase (DPMS) is a key enzyme in N- and O-linked glycosylations and glycosylphosphatidylinositol (GPI)-anchor synthesis. 26299246 9 3 theme Glycosylation 950:962 arg1 status 964:969 Glycosylation status 950:969 Glycosylation status of the marker protein 950:991 Glycosylation status of the marker protein was analyzed by Western blot. 26299246 6 4 theme radioactive 794:804 arg1 substrate 806:814 radioactive substrate 794:814 radioactive substrate 794:814 Gene expression and enzyme activities were measured using RT-PCR and radioactive substrate. 26299246 12 5 theme altered 1444:1450 arg1 composition 1462:1472 in altered cell wall composition 1441:1472 in altered cell wall composition 1441:1472 Lowered expression of DPMS genes results in decreased DPMS activity, increased susceptibility to cell wall perturbing agents and in altered cell wall composition. 26299246 12 6 theme in 1441:1442 arg1 composition 1462:1472 in altered cell wall composition 1441:1472 in altered cell wall composition 1441:1472 Lowered expression of DPMS genes results in decreased DPMS activity, increased susceptibility to cell wall perturbing agents and in altered cell wall composition. 26299246 15 7 theme yeast 1881:1885 arg1 albicans 1890:1897 pathogenic yeast C. albicans 1870:1897 pathogenic yeast C. albicans 1870:1897 GENERAL SIGNIFICANCE This work provides important data about factors required for a proper protein glycosylation and for morphogenesis of pathogenic yeast C. albicans. 26299246 1 8 theme key 162:164 arg1 enzyme 166:171 a key enzyme 160:171 a key enzyme in N- and O-linked glycosylations and glycosylphosphatidylinositol (GPI)-anchor synthesis 160:261 BACKGROUND Dolichol phosphate mannose synthase (DPMS) is a key enzyme in N- and O-linked glycosylations and glycosylphosphatidylinositol (GPI)-anchor synthesis. 26299246 1 8 theme key 162:164 arg1 synthase 141:148 BACKGROUND Dolichol phosphate mannose synthase 103:148 BACKGROUND Dolichol phosphate mannose synthase (DPMS) 103:155 BACKGROUND Dolichol phosphate mannose synthase (DPMS) is a key enzyme in N- and O-linked glycosylations and glycosylphosphatidylinositol (GPI)-anchor synthesis. 26299246 12 9 theme wall 1457:1460 arg1 composition 1462:1472 in altered cell wall composition 1441:1472 in altered cell wall composition 1441:1472 Lowered expression of DPMS genes results in decreased DPMS activity, increased susceptibility to cell wall perturbing agents and in altered cell wall composition. 26299246 13 10 from hyphae 1564:1569 arg1 impaired 1552:1559 impaired 1552:1559 impaired 1552:1559 Mutants Tetp-DPM1 and Tetp-DPM3 show defective protein glycosylation and are impaired in hyphae and chlamydospore formation. 26299246 9 11 theme marker 978:983 arg1 protein 985:991 the marker protein 974:991 the marker protein 974:991 Glycosylation status of the marker protein was analyzed by Western blot. 26299246 3 12 from emphasis 466:473 arg1 wall 487:490 the cell wall composition and morphogenesis 478:520 wall 487:490 Here we describe the role of DPMS for Candida albicans physiology with emphasis on the cell wall composition and morphogenesis. 26299246 3 12 from emphasis 466:473 arg1 morphogenesis 508:520 morphogenesis 508:520 morphogenesis 508:520 Here we describe the role of DPMS for Candida albicans physiology with emphasis on the cell wall composition and morphogenesis. 26299246 7 13 theme chemical 839:846 arg1 agents 848:853 chemical agents 839:853 chemical agents 839:853 Sensitivities against chemical agents were tested with microdilution method. 26299246 4 14 theme Saccharomyces 604:616 arg1 cerevisiae 618:627 Saccharomyces cerevisiae 604:627 Saccharomyces cerevisiae 604:627 METHODS C. albicans genes for DPMS subunits were cloned, tagged and expressed in Saccharomyces cerevisiae. 26299246 5 15 theme genes 688:692 arg1 expression 670:679 controlled expression 659:679 controlled expression of DPM genes 659:692 The C. albicans strains with controlled expression of DPM genes were constructed and analyzed. 26299246 10 16 theme Morphological 1023:1035 arg1 differentiation 1037:1051 Morphological differentiation 1023:1051 Morphological differentiation of the strains 1023:1066 Morphological differentiation of the strains was checked on the media promoting hyphae and chlamydospore formation. 26299246 12 17 theme increased 1381:1389 arg1 susceptibility 1391:1404 increased susceptibility 1381:1404 increased susceptibility to cell wall perturbing agents 1381:1435 Lowered expression of DPMS genes results in decreased DPMS activity, increased susceptibility to cell wall perturbing agents and in altered cell wall composition. 26299246 5 18 theme controlled 659:668 arg1 expression 670:679 controlled expression 659:679 controlled expression of DPM genes 659:692 The C. albicans strains with controlled expression of DPM genes were constructed and analyzed. 26299246 1 19 theme phosphate 123:131 arg1 enzyme 166:171 a key enzyme 160:171 a key enzyme in N- and O-linked glycosylations and glycosylphosphatidylinositol (GPI)-anchor synthesis 160:261 BACKGROUND Dolichol phosphate mannose synthase (DPMS) is a key enzyme in N- and O-linked glycosylations and glycosylphosphatidylinositol (GPI)-anchor synthesis. 26299246 1 19 theme phosphate 123:131 arg1 DPMS 151:154 DPMS 151:154 DPMS 151:154 BACKGROUND Dolichol phosphate mannose synthase (DPMS) is a key enzyme in N- and O-linked glycosylations and glycosylphosphatidylinositol (GPI)-anchor synthesis. 26299246 1 19 theme phosphate 123:131 arg1 synthase 141:148 BACKGROUND Dolichol phosphate mannose synthase 103:148 BACKGROUND Dolichol phosphate mannose synthase (DPMS) 103:155 BACKGROUND Dolichol phosphate mannose synthase (DPMS) is a key enzyme in N- and O-linked glycosylations and glycosylphosphatidylinositol (GPI)-anchor synthesis. 26299246 14 20 theme multimeric 1702:1711 arg1 structure 1721:1729 multimeric protein structure 1702:1729 multimeric protein structure 1702:1729 MAJOR CONCLUSION DPMS from C. albicans, opposite to S. cerevisiae, belongs to the family of DPMS with multimeric protein structure. 26299246 1 21 from enzyme 166:171 arg1 synthesis 253:261 glycosylphosphatidylinositol (GPI)-anchor synthesis 211:261 glycosylphosphatidylinositol (GPI)-anchor synthesis 211:261 BACKGROUND Dolichol phosphate mannose synthase (DPMS) is a key enzyme in N- and O-linked glycosylations and glycosylphosphatidylinositol (GPI)-anchor synthesis. 26299246 1 21 from enzyme 166:171 arg1 N- 176:177 N- 176:177 N- 176:177 BACKGROUND Dolichol phosphate mannose synthase (DPMS) is a key enzyme in N- and O-linked glycosylations and glycosylphosphatidylinositol (GPI)-anchor synthesis. 26299246 1 21 from enzyme 166:171 arg1 glycosylations 192:205 O-linked glycosylations 183:205 O-linked glycosylations 183:205 BACKGROUND Dolichol phosphate mannose synthase (DPMS) is a key enzyme in N- and O-linked glycosylations and glycosylphosphatidylinositol (GPI)-anchor synthesis. 26299246 12 22 theme decreased 1356:1364 arg1 activity 1371:1378 decreased DPMS activity 1356:1378 decreased DPMS activity 1356:1378 Lowered expression of DPMS genes results in decreased DPMS activity, increased susceptibility to cell wall perturbing agents and in altered cell wall composition. 26299246 13 23 from impaired 1552:1559 arg1 hyphae 1564:1569 hyphae 1564:1569 hyphae 1564:1569 Mutants Tetp-DPM1 and Tetp-DPM3 show defective protein glycosylation and are impaired in hyphae and chlamydospore formation. 26299246 13 23 from impaired 1552:1559 arg1 formation 1589:1597 chlamydospore formation 1575:1597 chlamydospore formation 1575:1597 Mutants Tetp-DPM1 and Tetp-DPM3 show defective protein glycosylation and are impaired in hyphae and chlamydospore formation. 26299246 0 24 theme Candida 62:68 arg1 albicans 70:77 the pathogenic yeast Candida albicans 41:77 the pathogenic yeast Candida albicans 41:77 Dolichol phosphate mannose synthase from the pathogenic yeast Candida albicans is a multimeric enzyme. 26299246 14 25 theme DPMS 1692:1695 arg1 family 1682:1687 the family 1678:1687 the family of DPMS with multimeric protein structure 1678:1729 MAJOR CONCLUSION DPMS from C. albicans, opposite to S. cerevisiae, belongs to the family of DPMS with multimeric protein structure. 26299246 13 26 theme chlamydospore 1575:1587 arg1 formation 1589:1597 chlamydospore formation 1575:1597 chlamydospore formation 1575:1597 Mutants Tetp-DPM1 and Tetp-DPM3 show defective protein glycosylation and are impaired in hyphae and chlamydospore formation. 26299246 15 27 theme albicans 1890:1897 arg1 morphogenesis 1853:1865 morphogenesis 1853:1865 morphogenesis of pathogenic yeast C. albicans 1853:1897 GENERAL SIGNIFICANCE This work provides important data about factors required for a proper protein glycosylation and for morphogenesis of pathogenic yeast C. albicans. 26299246 1 28 link O-linked 183:190 arg1 glycosylations 192:205 O-linked glycosylations 183:205 O-linked glycosylations 183:205 BACKGROUND Dolichol phosphate mannose synthase (DPMS) is a key enzyme in N- and O-linked glycosylations and glycosylphosphatidylinositol (GPI)-anchor synthesis. 26299246 10 29 theme strains 1060:1066 arg1 differentiation 1037:1051 Morphological differentiation 1023:1051 Morphological differentiation of the strains 1023:1066 Morphological differentiation of the strains was checked on the media promoting hyphae and chlamydospore formation. 26299246 14 30 theme MAJOR 1600:1604 arg1 DPMS 1617:1620 MAJOR CONCLUSION DPMS 1600:1620 MAJOR CONCLUSION DPMS 1600:1620 MAJOR CONCLUSION DPMS from C. albicans, opposite to S. cerevisiae, belongs to the family of DPMS with multimeric protein structure. 26299246 0 31 theme multimeric 84:93 arg1 enzyme 95:100 a multimeric enzyme 82:100 a multimeric enzyme 82:100 Dolichol phosphate mannose synthase from the pathogenic yeast Candida albicans is a multimeric enzyme. 26299246 0 31 theme multimeric 84:93 arg1 synthase 27:34 Dolichol phosphate mannose synthase 0:34 Dolichol phosphate mannose synthase from the pathogenic yeast Candida albicans 0:77 Dolichol phosphate mannose synthase from the pathogenic yeast Candida albicans is a multimeric enzyme. 26299246 11 32 theme interacting 1202:1212 arg1 subunits 1214:1221 three interacting subunits 1196:1221 three interacting subunits 1196:1221 RESULTS We demonstrate that C. albicans DPMS consists of three interacting subunits, among which Dpm1 and Dpm3 are indispensable, whereas Dpm2 increases enzymatic activity. 26299246 3 33 theme albicans 441:448 arg1 physiology 450:459 Candida albicans physiology 433:459 Candida albicans physiology 433:459 Here we describe the role of DPMS for Candida albicans physiology with emphasis on the cell wall composition and morphogenesis. 26299246 2 34 theme dolichol 375:382 arg1 phosphate 384:392 dolichol phosphate 375:392 dolichol phosphate 375:392 DPMS generates DPM, the substrate for mentioned processes, by the transfer of mannosyl residue from GDP-Man to dolichol phosphate. 26299246 12 35 theme Lowered 1312:1318 arg1 expression 1320:1329 Lowered expression 1312:1329 Lowered expression of DPMS genes 1312:1343 Lowered expression of DPMS genes results in decreased DPMS activity, increased susceptibility to cell wall perturbing agents and in altered cell wall composition. 26299246 0 36 theme Dolichol 0:7 arg1 enzyme 95:100 a multimeric enzyme 82:100 a multimeric enzyme 82:100 Dolichol phosphate mannose synthase from the pathogenic yeast Candida albicans is a multimeric enzyme. 26299246 0 36 theme Dolichol 0:7 arg1 synthase 27:34 Dolichol phosphate mannose synthase 0:34 Dolichol phosphate mannose synthase from the pathogenic yeast Candida albicans 0:77 Dolichol phosphate mannose synthase from the pathogenic yeast Candida albicans is a multimeric enzyme. 26299246 3 37 theme Candida 433:439 arg1 albicans 441:448 Candida albicans 433:448 Candida albicans physiology 433:459 Here we describe the role of DPMS for Candida albicans physiology with emphasis on the cell wall composition and morphogenesis. 26299246 0 38 theme mannose 19:25 arg1 enzyme 95:100 a multimeric enzyme 82:100 a multimeric enzyme 82:100 Dolichol phosphate mannose synthase from the pathogenic yeast Candida albicans is a multimeric enzyme. 26299246 0 38 theme mannose 19:25 arg1 synthase 27:34 Dolichol phosphate mannose synthase 0:34 Dolichol phosphate mannose synthase from the pathogenic yeast Candida albicans 0:77 Dolichol phosphate mannose synthase from the pathogenic yeast Candida albicans is a multimeric enzyme. 26299246 1 39 theme BACKGROUND 103:112 arg1 enzyme 166:171 a key enzyme 160:171 a key enzyme in N- and O-linked glycosylations and glycosylphosphatidylinositol (GPI)-anchor synthesis 160:261 BACKGROUND Dolichol phosphate mannose synthase (DPMS) is a key enzyme in N- and O-linked glycosylations and glycosylphosphatidylinositol (GPI)-anchor synthesis. 26299246 1 39 theme BACKGROUND 103:112 arg1 DPMS 151:154 DPMS 151:154 DPMS 151:154 BACKGROUND Dolichol phosphate mannose synthase (DPMS) is a key enzyme in N- and O-linked glycosylations and glycosylphosphatidylinositol (GPI)-anchor synthesis. 26299246 1 39 theme BACKGROUND 103:112 arg1 synthase 141:148 BACKGROUND Dolichol phosphate mannose synthase 103:148 BACKGROUND Dolichol phosphate mannose synthase (DPMS) 103:155 BACKGROUND Dolichol phosphate mannose synthase (DPMS) is a key enzyme in N- and O-linked glycosylations and glycosylphosphatidylinositol (GPI)-anchor synthesis. 26299246 8 40 theme wall 922:925 arg1 composition 898:908 The composition 894:908 The composition of the cell wall 894:925 The composition of the cell wall was estimated by HPLC. 26299246 3 41 theme DPMS 424:427 arg1 role 416:419 the role 412:419 the role of DPMS for Candida albicans physiology 412:459 Here we describe the role of DPMS for Candida albicans physiology with emphasis on the cell wall composition and morphogenesis. 26299246 15 42 theme proper 1816:1821 arg1 glycosylation 1831:1843 a proper protein glycosylation 1814:1843 a proper protein glycosylation 1814:1843 GENERAL SIGNIFICANCE This work provides important data about factors required for a proper protein glycosylation and for morphogenesis of pathogenic yeast C. albicans. 26299246 13 43 theme defective 1512:1520 arg1 glycosylation 1530:1542 defective protein glycosylation 1512:1542 defective protein glycosylation 1512:1542 Mutants Tetp-DPM1 and Tetp-DPM3 show defective protein glycosylation and are impaired in hyphae and chlamydospore formation. 26299246 2 44 from GDP-Man 364:370 arg1 transfer 330:337 the transfer 326:337 the transfer of mannosyl residue from GDP-Man to dolichol phosphate 326:392 DPMS generates DPM, the substrate for mentioned processes, by the transfer of mannosyl residue from GDP-Man to dolichol phosphate. 26299246 6 45 theme enzyme 745:750 arg1 activities 752:761 enzyme activities 745:761 enzyme activities 745:761 Gene expression and enzyme activities were measured using RT-PCR and radioactive substrate. 26299246 0 46 theme pathogenic 45:54 arg1 albicans 70:77 the pathogenic yeast Candida albicans 41:77 the pathogenic yeast Candida albicans 41:77 Dolichol phosphate mannose synthase from the pathogenic yeast Candida albicans is a multimeric enzyme. 26299246 4 47 dep METHODS 523:529 arg1 genes 543:547 C. albicans genes 531:547 METHODS C. albicans genes for DPMS subunits 523:565 METHODS C. albicans genes for DPMS subunits were cloned, tagged and expressed in Saccharomyces cerevisiae. 26299246 14 48 from albicans 1630:1637 arg1 DPMS 1617:1620 MAJOR CONCLUSION DPMS 1600:1620 MAJOR CONCLUSION DPMS 1600:1620 MAJOR CONCLUSION DPMS from C. albicans, opposite to S. cerevisiae, belongs to the family of DPMS with multimeric protein structure. 26299246 2 49 theme residue 351:357 arg1 transfer 330:337 the transfer 326:337 the transfer of mannosyl residue from GDP-Man to dolichol phosphate 326:392 DPMS generates DPM, the substrate for mentioned processes, by the transfer of mannosyl residue from GDP-Man to dolichol phosphate. 26299246 11 50 theme C. 1167:1168 arg1 DPMS 1179:1182 C. albicans DPMS 1167:1182 C. albicans DPMS 1167:1182 RESULTS We demonstrate that C. albicans DPMS consists of three interacting subunits, among which Dpm1 and Dpm3 are indispensable, whereas Dpm2 increases enzymatic activity. 26299246 5 51 with strains 646:652 arg1 expression 670:679 controlled expression 659:679 controlled expression of DPM genes 659:692 The C. albicans strains with controlled expression of DPM genes were constructed and analyzed. 26299246 4 52 theme DPMS 553:556 arg1 subunits 558:565 DPMS subunits 553:565 DPMS subunits 553:565 METHODS C. albicans genes for DPMS subunits were cloned, tagged and expressed in Saccharomyces cerevisiae. 26299246 15 53 theme C. 1887:1888 arg1 albicans 1890:1897 pathogenic yeast C. albicans 1870:1897 pathogenic yeast C. albicans 1870:1897 GENERAL SIGNIFICANCE This work provides important data about factors required for a proper protein glycosylation and for morphogenesis of pathogenic yeast C. albicans. 26299246 12 54 theme cell 1452:1455 arg1 composition 1462:1472 in altered cell wall composition 1441:1472 in altered cell wall composition 1441:1472 Lowered expression of DPMS genes results in decreased DPMS activity, increased susceptibility to cell wall perturbing agents and in altered cell wall composition. 26299246 15 55 theme pathogenic 1870:1879 arg1 albicans 1890:1897 pathogenic yeast C. albicans 1870:1897 pathogenic yeast C. albicans 1870:1897 GENERAL SIGNIFICANCE This work provides important data about factors required for a proper protein glycosylation and for morphogenesis of pathogenic yeast C. albicans. 26299246 15 56 theme GENERAL 1732:1738 arg1 SIGNIFICANCE 1740:1751 GENERAL SIGNIFICANCE 1732:1751 GENERAL SIGNIFICANCE This work provides important data about factors required for a proper protein glycosylation and for morphogenesis of pathogenic yeast C. albicans 1732:1897 GENERAL SIGNIFICANCE This work provides important data about factors required for a proper protein glycosylation and for morphogenesis of pathogenic yeast C. albicans. 26299246 7 57 theme microdilution 872:884 arg1 method 886:891 microdilution method 872:891 microdilution method 872:891 Sensitivities against chemical agents were tested with microdilution method. 26299246 13 58 dep Mutants 1475:1481 arg1 Mutants 1475:1481 Mutants Tetp-DPM1 and Tetp-DPM3 1475:1505 Mutants Tetp-DPM1 and Tetp-DPM3 1475:1505 Mutants Tetp-DPM1 and Tetp-DPM3 show defective protein glycosylation and are impaired in hyphae and chlamydospore formation. 26299246 13 58 dep Mutants 1475:1481 arg1 Tetp-DPM3 1497:1505 Tetp-DPM3 1497:1505 Tetp-DPM3 1497:1505 Mutants Tetp-DPM1 and Tetp-DPM3 show defective protein glycosylation and are impaired in hyphae and chlamydospore formation. 26299246 13 58 dep Mutants 1475:1481 arg1 Tetp-DPM1 1483:1491 Tetp-DPM1 1483:1491 Tetp-DPM1 1483:1491 Mutants Tetp-DPM1 and Tetp-DPM3 show defective protein glycosylation and are impaired in hyphae and chlamydospore formation. 26299246 2 59 theme mentioned 302:310 arg1 processes 312:320 mentioned processes 302:320 mentioned processes 302:320 DPMS generates DPM, the substrate for mentioned processes, by the transfer of mannosyl residue from GDP-Man to dolichol phosphate. 26299246 14 60 theme C. 1627:1628 arg1 albicans 1630:1637 C. albicans 1627:1637 C. albicans 1627:1637 MAJOR CONCLUSION DPMS from C. albicans, opposite to S. cerevisiae, belongs to the family of DPMS with multimeric protein structure. 26299246 9 61 theme protein 985:991 arg1 status 964:969 Glycosylation status 950:969 Glycosylation status of the marker protein 950:991 Glycosylation status of the marker protein was analyzed by Western blot. 26299246 5 62 theme DPM 684:686 arg1 genes 688:692 DPM genes 684:692 DPM genes 684:692 The C. albicans strains with controlled expression of DPM genes were constructed and analyzed. 26299246 12 63 theme cell 1409:1412 arg1 wall 1414:1417 cell wall 1409:1417 cell wall perturbing agents 1409:1435 Lowered expression of DPMS genes results in decreased DPMS activity, increased susceptibility to cell wall perturbing agents and in altered cell wall composition. 26299246 13 64 from formation 1589:1597 arg1 impaired 1552:1559 impaired 1552:1559 impaired 1552:1559 Mutants Tetp-DPM1 and Tetp-DPM3 show defective protein glycosylation and are impaired in hyphae and chlamydospore formation. 26299246 1 65 theme O-linked 183:190 arg1 glycosylations 192:205 O-linked glycosylations 183:205 O-linked glycosylations 183:205 BACKGROUND Dolichol phosphate mannose synthase (DPMS) is a key enzyme in N- and O-linked glycosylations and glycosylphosphatidylinositol (GPI)-anchor synthesis. 26299246 0 66 from albicans 70:77 arg1 enzyme 95:100 a multimeric enzyme 82:100 a multimeric enzyme 82:100 Dolichol phosphate mannose synthase from the pathogenic yeast Candida albicans is a multimeric enzyme. 26299246 0 66 from albicans 70:77 arg1 synthase 27:34 Dolichol phosphate mannose synthase 0:34 Dolichol phosphate mannose synthase from the pathogenic yeast Candida albicans 0:77 Dolichol phosphate mannose synthase from the pathogenic yeast Candida albicans is a multimeric enzyme. 26299246 12 67 theme DPMS 1366:1369 arg1 activity 1371:1378 decreased DPMS activity 1356:1378 decreased DPMS activity 1356:1378 Lowered expression of DPMS genes results in decreased DPMS activity, increased susceptibility to cell wall perturbing agents and in altered cell wall composition. 26299246 9 68 theme Western 1009:1015 arg1 blot 1017:1020 Western blot 1009:1020 Western blot 1009:1020 Glycosylation status of the marker protein was analyzed by Western blot. 26299246 1 69 theme Dolichol 114:121 arg1 enzyme 166:171 a key enzyme 160:171 a key enzyme in N- and O-linked glycosylations and glycosylphosphatidylinositol (GPI)-anchor synthesis 160:261 BACKGROUND Dolichol phosphate mannose synthase (DPMS) is a key enzyme in N- and O-linked glycosylations and glycosylphosphatidylinositol (GPI)-anchor synthesis. 26299246 1 69 theme Dolichol 114:121 arg1 DPMS 151:154 DPMS 151:154 DPMS 151:154 BACKGROUND Dolichol phosphate mannose synthase (DPMS) is a key enzyme in N- and O-linked glycosylations and glycosylphosphatidylinositol (GPI)-anchor synthesis. 26299246 1 69 theme Dolichol 114:121 arg1 synthase 141:148 BACKGROUND Dolichol phosphate mannose synthase 103:148 BACKGROUND Dolichol phosphate mannose synthase (DPMS) 103:155 BACKGROUND Dolichol phosphate mannose synthase (DPMS) is a key enzyme in N- and O-linked glycosylations and glycosylphosphatidylinositol (GPI)-anchor synthesis. 26299246 14 70 theme opposite 1640:1647 arg1 DPMS 1617:1620 MAJOR CONCLUSION DPMS 1600:1620 MAJOR CONCLUSION DPMS 1600:1620 MAJOR CONCLUSION DPMS from C. albicans, opposite to S. cerevisiae, belongs to the family of DPMS with multimeric protein structure. 26299246 14 71 theme protein 1713:1719 arg1 structure 1721:1729 multimeric protein structure 1702:1729 multimeric protein structure 1702:1729 MAJOR CONCLUSION DPMS from C. albicans, opposite to S. cerevisiae, belongs to the family of DPMS with multimeric protein structure. 26299246 1 72 theme mannose 133:139 arg1 enzyme 166:171 a key enzyme 160:171 a key enzyme in N- and O-linked glycosylations and glycosylphosphatidylinositol (GPI)-anchor synthesis 160:261 BACKGROUND Dolichol phosphate mannose synthase (DPMS) is a key enzyme in N- and O-linked glycosylations and glycosylphosphatidylinositol (GPI)-anchor synthesis. 26299246 1 72 theme mannose 133:139 arg1 DPMS 151:154 DPMS 151:154 DPMS 151:154 BACKGROUND Dolichol phosphate mannose synthase (DPMS) is a key enzyme in N- and O-linked glycosylations and glycosylphosphatidylinositol (GPI)-anchor synthesis. 26299246 1 72 theme mannose 133:139 arg1 synthase 141:148 BACKGROUND Dolichol phosphate mannose synthase 103:148 BACKGROUND Dolichol phosphate mannose synthase (DPMS) 103:155 BACKGROUND Dolichol phosphate mannose synthase (DPMS) is a key enzyme in N- and O-linked glycosylations and glycosylphosphatidylinositol (GPI)-anchor synthesis. 26299246 12 73 theme genes 1339:1343 arg1 expression 1320:1329 Lowered expression 1312:1329 Lowered expression of DPMS genes 1312:1343 Lowered expression of DPMS genes results in decreased DPMS activity, increased susceptibility to cell wall perturbing agents and in altered cell wall composition. 26299246 15 74 theme important 1772:1780 arg1 data 1782:1785 important data 1772:1785 important data about factors required for a proper protein glycosylation and for morphogenesis of pathogenic yeast C. albicans 1772:1897 GENERAL SIGNIFICANCE This work provides important data about factors required for a proper protein glycosylation and for morphogenesis of pathogenic yeast C. albicans. 26299246 14 75 theme CONCLUSION 1606:1615 arg1 DPMS 1617:1620 MAJOR CONCLUSION DPMS 1600:1620 MAJOR CONCLUSION DPMS 1600:1620 MAJOR CONCLUSION DPMS from C. albicans, opposite to S. cerevisiae, belongs to the family of DPMS with multimeric protein structure. 26299246 11 76 theme enzymatic 1292:1300 arg1 activity 1302:1309 enzymatic activity 1292:1309 enzymatic activity 1292:1309 RESULTS We demonstrate that C. albicans DPMS consists of three interacting subunits, among which Dpm1 and Dpm3 are indispensable, whereas Dpm2 increases enzymatic activity. 26299246 10 77 theme chlamydospore 1114:1126 arg1 formation 1128:1136 chlamydospore formation 1114:1136 chlamydospore formation 1114:1136 Morphological differentiation of the strains was checked on the media promoting hyphae and chlamydospore formation. 26299246 11 78 dep RESULTS 1139:1145 arg1 demonstrate 1150:1160 demonstrate 1150:1160 demonstrate that C. albicans DPMS consists of three interacting subunits, among which Dpm1 and Dpm3 are indispensable, whereas Dpm2 increases enzymatic activity 1150:1309 RESULTS We demonstrate that C. albicans DPMS consists of three interacting subunits, among which Dpm1 and Dpm3 are indispensable, whereas Dpm2 increases enzymatic activity. 26299246 0 79 theme phosphate 9:17 arg1 enzyme 95:100 a multimeric enzyme 82:100 a multimeric enzyme 82:100 Dolichol phosphate mannose synthase from the pathogenic yeast Candida albicans is a multimeric enzyme. 26299246 0 79 theme phosphate 9:17 arg1 synthase 27:34 Dolichol phosphate mannose synthase 0:34 Dolichol phosphate mannose synthase from the pathogenic yeast Candida albicans 0:77 Dolichol phosphate mannose synthase from the pathogenic yeast Candida albicans is a multimeric enzyme. 26299246 12 80 theme DPMS 1334:1337 arg1 genes 1339:1343 DPMS genes 1334:1343 DPMS genes 1334:1343 Lowered expression of DPMS genes results in decreased DPMS activity, increased susceptibility to cell wall perturbing agents and in altered cell wall composition. 26299246 4 81 theme albicans 534:541 arg1 genes 543:547 C. albicans genes 531:547 METHODS C. albicans genes for DPMS subunits 523:565 METHODS C. albicans genes for DPMS subunits were cloned, tagged and expressed in Saccharomyces cerevisiae. 26299246 15 82 theme protein 1823:1829 arg1 glycosylation 1831:1843 a proper protein glycosylation 1814:1843 a proper protein glycosylation 1814:1843 GENERAL SIGNIFICANCE This work provides important data about factors required for a proper protein glycosylation and for morphogenesis of pathogenic yeast C. albicans. 26299246 3 83 dep wall 487:490 arg1 composition 492:502 composition 492:502 composition 492:502 Here we describe the role of DPMS for Candida albicans physiology with emphasis on the cell wall composition and morphogenesis. 26299246 5 84 dep C. 634:635 arg1 albicans 637:644 albicans 637:644 albicans 637:644 The C. albicans strains with controlled expression of DPM genes were constructed and analyzed. 26299246 11 85 dep C. 1167:1168 arg1 albicans 1170:1177 albicans 1170:1177 albicans 1170:1177 RESULTS We demonstrate that C. albicans DPMS consists of three interacting subunits, among which Dpm1 and Dpm3 are indispensable, whereas Dpm2 increases enzymatic activity. 26299246 8 86 theme cell 917:920 arg1 wall 922:925 the cell wall 913:925 the cell wall 913:925 The composition of the cell wall was estimated by HPLC. 26299246 13 87 theme protein 1522:1528 arg1 glycosylation 1530:1542 defective protein glycosylation 1512:1542 defective protein glycosylation 1512:1542 Mutants Tetp-DPM1 and Tetp-DPM3 show defective protein glycosylation and are impaired in hyphae and chlamydospore formation. 26299246 0 88 theme yeast 56:60 arg1 albicans 70:77 the pathogenic yeast Candida albicans 41:77 the pathogenic yeast Candida albicans 41:77 Dolichol phosphate mannose synthase from the pathogenic yeast Candida albicans is a multimeric enzyme. 26299246 14 89 with DPMS 1692:1695 arg1 structure 1721:1729 multimeric protein structure 1702:1729 multimeric protein structure 1702:1729 MAJOR CONCLUSION DPMS from C. albicans, opposite to S. cerevisiae, belongs to the family of DPMS with multimeric protein structure. 26299246 6 90 theme Gene 725:728 arg1 expression 730:739 Gene expression 725:739 Gene expression 725:739 Gene expression and enzyme activities were measured using RT-PCR and radioactive substrate. 26299246 15 91 dep SIGNIFICANCE 1740:1751 arg1 provides 1763:1770 provides 1763:1770 provides important data about factors required for a proper protein glycosylation and for morphogenesis of pathogenic yeast C. albicans 1763:1897 GENERAL SIGNIFICANCE This work provides important data about factors required for a proper protein glycosylation and for morphogenesis of pathogenic yeast C. albicans. 26299246 1 92 theme glycosylphosphatidylinositol 211:238 arg1 synthesis 253:261 glycosylphosphatidylinositol (GPI)-anchor synthesis 211:261 glycosylphosphatidylinositol (GPI)-anchor synthesis 211:261 BACKGROUND Dolichol phosphate mannose synthase (DPMS) is a key enzyme in N- and O-linked glycosylations and glycosylphosphatidylinositol (GPI)-anchor synthesis. 26299246 2 93 theme mannosyl 342:349 arg1 residue 351:357 mannosyl residue 342:357 mannosyl residue 342:357 DPMS generates DPM, the substrate for mentioned processes, by the transfer of mannosyl residue from GDP-Man to dolichol phosphate. 26148948 10 0 theme therapeutic 1657:1667 arg1 approach 1669:1676 an adequate and targeted therapeutic approach 1632:1676 an adequate and targeted therapeutic approach for MLT 1632:1684 Because of its antiangiogenic properties, including anti-lymphangiogenesis, sirolimus offers an adequate and targeted therapeutic approach for MLT. 26148948 8 1 attach presents 1286:1293 arg2 MLT 1271:1273 MLT 1271:1273 MLT 1271:1273 MLT clinically presents in various forms, and when complicated by widespread or severe extracutaneous involvement, initial aggressive therapeutic intervention is justified. 26148948 8 1 attach presents 1286:1293 arg1 forms 1306:1310 various forms 1298:1310 various forms 1298:1310 MLT clinically presents in various forms, and when complicated by widespread or severe extracutaneous involvement, initial aggressive therapeutic intervention is justified. 26148948 5 2 theme various 715:721 arg1 phenotypes 747:756 various clinical and biological phenotypes 715:756 various clinical and biological phenotypes of MLT 715:763 We report 3 newborn cases featuring various clinical and biological phenotypes of MLT: 1 patient had severe brain involvement and died early; another had no thrombocytopenia; and the third had nearly no skin involvement. 26148948 1 3 theme described 188:196 arg1 lymphangioendotheliomatosis 118:144 Multifocal lymphangioendotheliomatosis 107:144 Multifocal lymphangioendotheliomatosis with thrombocytopenia (MLT) 107:172 Multifocal lymphangioendotheliomatosis with thrombocytopenia (MLT) is a recently described glucose transporter 1-negative multifocal vascular disorder with significant morbidity and mortality. 26148948 1 3 theme described 188:196 arg1 disorder 249:256 a recently described glucose transporter 1-negative multifocal vascular disorder 177:256 a recently described glucose transporter 1-negative multifocal vascular disorder with significant morbidity and mortality 177:297 Multifocal lymphangioendotheliomatosis with thrombocytopenia (MLT) is a recently described glucose transporter 1-negative multifocal vascular disorder with significant morbidity and mortality. 26148948 9 4 theme lymphatic 1489:1497 arg1 differentiation 1499:1513 lymphatic differentiation 1489:1513 lymphatic differentiation 1489:1513 The pathogenesis of MLT remains unclear, but lymphatic differentiation is widely acknowledged. 26148948 10 5 theme targeted 1648:1655 arg1 approach 1669:1676 an adequate and targeted therapeutic approach 1632:1676 an adequate and targeted therapeutic approach for MLT 1632:1684 Because of its antiangiogenic properties, including anti-lymphangiogenesis, sirolimus offers an adequate and targeted therapeutic approach for MLT. 26148948 5 6 theme clinical 723:730 arg1 phenotypes 747:756 various clinical and biological phenotypes 715:756 various clinical and biological phenotypes of MLT 715:763 We report 3 newborn cases featuring various clinical and biological phenotypes of MLT: 1 patient had severe brain involvement and died early; another had no thrombocytopenia; and the third had nearly no skin involvement. 26148948 1 7 theme glucose 198:204 arg1 lymphangioendotheliomatosis 118:144 Multifocal lymphangioendotheliomatosis 107:144 Multifocal lymphangioendotheliomatosis with thrombocytopenia (MLT) 107:172 Multifocal lymphangioendotheliomatosis with thrombocytopenia (MLT) is a recently described glucose transporter 1-negative multifocal vascular disorder with significant morbidity and mortality. 26148948 1 7 theme glucose 198:204 arg1 disorder 249:256 a recently described glucose transporter 1-negative multifocal vascular disorder 177:256 a recently described glucose transporter 1-negative multifocal vascular disorder with significant morbidity and mortality 177:297 Multifocal lymphangioendotheliomatosis with thrombocytopenia (MLT) is a recently described glucose transporter 1-negative multifocal vascular disorder with significant morbidity and mortality. 26148948 4 8 theme infantile 635:643 arg1 hemangioma 645:654 infantile hemangioma 635:654 infantile hemangioma 635:654 Treatments for MLT have been disappointing, and the treatments classically used for infantile hemangioma are often ineffective. 26148948 5 9 theme brain 787:791 arg1 involvement 793:803 severe brain involvement 780:803 severe brain involvement 780:803 We report 3 newborn cases featuring various clinical and biological phenotypes of MLT: 1 patient had severe brain involvement and died early; another had no thrombocytopenia; and the third had nearly no skin involvement. 26148948 7 10 theme sirolimus 1187:1195 arg1 mg/k 1201:1204 sirolimus 0.1 mg/k 1187:1204 sirolimus 0.1 mg/k 1187:1204 Two cases with severe gastrointestinal bleeding were treated with sirolimus 0.1 mg/k per day, which was efficient after the first month of treatment. 26148948 6 11 link O-linked 1067:1074 arg1 D2-40 1052:1056 D2-40 1052:1056 D2-40 (∼38-kDa O-linked transmembrane sialoglycoprotein podoplanin) 1052:1118 Histologically, all were negative for glucose transporter 1 and positive for the lymphatic marker lymphatic vessel endothelial hyaluronan receptor 1 or D2-40 (∼38-kDa O-linked transmembrane sialoglycoprotein podoplanin). 26148948 6 11 link O-linked 1067:1074 arg1 podoplanin 1108:1117 ∼38-kDa O-linked transmembrane sialoglycoprotein podoplanin 1059:1117 ∼38-kDa O-linked transmembrane sialoglycoprotein podoplanin 1059:1117 Histologically, all were negative for glucose transporter 1 and positive for the lymphatic marker lymphatic vessel endothelial hyaluronan receptor 1 or D2-40 (∼38-kDa O-linked transmembrane sialoglycoprotein podoplanin). 26148948 2 12 theme clinical 333:340 arg1 spectrum 342:349 clinical spectrum 333:349 clinical spectrum 333:349 However, data are lacking on the clinical spectrum, long-term prognosis, and treatment of MLT. 26148948 2 13 dep spectrum 342:349 arg1 the 329:331 the 329:331 the 329:331 However, data are lacking on the clinical spectrum, long-term prognosis, and treatment of MLT. 26148948 6 14 theme glucose 938:944 arg1 transporter 946:956 glucose transporter 1 938:958 glucose transporter 1 938:958 Histologically, all were negative for glucose transporter 1 and positive for the lymphatic marker lymphatic vessel endothelial hyaluronan receptor 1 or D2-40 (∼38-kDa O-linked transmembrane sialoglycoprotein podoplanin). 26148948 5 15 dep cases 699:703 arg1 had 868:870 had 868:870 had nearly no skin involvement 868:897 We report 3 newborn cases featuring various clinical and biological phenotypes of MLT: 1 patient had severe brain involvement and died early; another had no thrombocytopenia; and the third had nearly no skin involvement. 26148948 5 15 dep cases 699:703 arg1 died 809:812 died 809:812 died early 809:818 We report 3 newborn cases featuring various clinical and biological phenotypes of MLT: 1 patient had severe brain involvement and died early; another had no thrombocytopenia; and the third had nearly no skin involvement. 26148948 5 15 dep cases 699:703 arg1 had 776:778 had 776:778 had severe brain involvement 776:803 We report 3 newborn cases featuring various clinical and biological phenotypes of MLT: 1 patient had severe brain involvement and died early; another had no thrombocytopenia; and the third had nearly no skin involvement. 26148948 5 15 dep cases 699:703 arg1 had 829:831 had 829:831 had no thrombocytopenia 829:851 We report 3 newborn cases featuring various clinical and biological phenotypes of MLT: 1 patient had severe brain involvement and died early; another had no thrombocytopenia; and the third had nearly no skin involvement. 26148948 1 16 theme transporter 206:216 arg1 lymphangioendotheliomatosis 118:144 Multifocal lymphangioendotheliomatosis 107:144 Multifocal lymphangioendotheliomatosis with thrombocytopenia (MLT) 107:172 Multifocal lymphangioendotheliomatosis with thrombocytopenia (MLT) is a recently described glucose transporter 1-negative multifocal vascular disorder with significant morbidity and mortality. 26148948 1 16 theme transporter 206:216 arg1 disorder 249:256 a recently described glucose transporter 1-negative multifocal vascular disorder 177:256 a recently described glucose transporter 1-negative multifocal vascular disorder with significant morbidity and mortality 177:297 Multifocal lymphangioendotheliomatosis with thrombocytopenia (MLT) is a recently described glucose transporter 1-negative multifocal vascular disorder with significant morbidity and mortality. 26148948 5 17 theme newborn 691:697 arg1 cases 699:703 3 newborn cases 689:703 3 newborn cases featuring various clinical and biological phenotypes of MLT: 1 patient had severe brain involvement and died early; another had no thrombocytopenia; and the third had nearly no skin involvement 689:897 We report 3 newborn cases featuring various clinical and biological phenotypes of MLT: 1 patient had severe brain involvement and died early; another had no thrombocytopenia; and the third had nearly no skin involvement. 26148948 7 18 theme treatment 1260:1268 arg1 month 1251:1255 the first month 1241:1255 the first month of treatment 1241:1268 Two cases with severe gastrointestinal bleeding were treated with sirolimus 0.1 mg/k per day, which was efficient after the first month of treatment. 26148948 0 19 theme Multifocal 0:9 arg1 Lymphangioendotheliomatosis 11:37 Multifocal Lymphangioendotheliomatosis 0:37 Multifocal Lymphangioendotheliomatosis With Thrombocytopenia: Clinical Features and Response to Sirolimus. 0:105 Multifocal Lymphangioendotheliomatosis With Thrombocytopenia: Clinical Features and Response to Sirolimus. 26148948 1 20 theme 1-negative 218:227 arg1 lymphangioendotheliomatosis 118:144 Multifocal lymphangioendotheliomatosis 107:144 Multifocal lymphangioendotheliomatosis with thrombocytopenia (MLT) 107:172 Multifocal lymphangioendotheliomatosis with thrombocytopenia (MLT) is a recently described glucose transporter 1-negative multifocal vascular disorder with significant morbidity and mortality. 26148948 1 20 theme 1-negative 218:227 arg1 disorder 249:256 a recently described glucose transporter 1-negative multifocal vascular disorder 177:256 a recently described glucose transporter 1-negative multifocal vascular disorder with significant morbidity and mortality 177:297 Multifocal lymphangioendotheliomatosis with thrombocytopenia (MLT) is a recently described glucose transporter 1-negative multifocal vascular disorder with significant morbidity and mortality. 26148948 3 21 theme multifocal 421:430 arg1 hemangioma 442:451 multifocal infantile hemangioma 421:451 multifocal infantile hemangioma 421:451 It is often confused with multifocal infantile hemangioma, but the conditions must be differentiated for appropriate assessment and therapeutic management. 26148948 10 22 theme antiangiogenic 1554:1567 arg1 properties 1569:1578 its antiangiogenic properties 1550:1578 its antiangiogenic properties 1550:1578 Because of its antiangiogenic properties, including anti-lymphangiogenesis, sirolimus offers an adequate and targeted therapeutic approach for MLT. 26148948 10 22 theme antiangiogenic 1554:1567 arg1 anti-lymphangiogenesis 1591:1612 anti-lymphangiogenesis 1591:1612 anti-lymphangiogenesis 1591:1612 Because of its antiangiogenic properties, including anti-lymphangiogenesis, sirolimus offers an adequate and targeted therapeutic approach for MLT. 26148948 1 23 theme Multifocal 107:116 arg1 lymphangioendotheliomatosis 118:144 Multifocal lymphangioendotheliomatosis 107:144 Multifocal lymphangioendotheliomatosis with thrombocytopenia (MLT) 107:172 Multifocal lymphangioendotheliomatosis with thrombocytopenia (MLT) is a recently described glucose transporter 1-negative multifocal vascular disorder with significant morbidity and mortality. 26148948 1 23 theme Multifocal 107:116 arg1 disorder 249:256 a recently described glucose transporter 1-negative multifocal vascular disorder 177:256 a recently described glucose transporter 1-negative multifocal vascular disorder with significant morbidity and mortality 177:297 Multifocal lymphangioendotheliomatosis with thrombocytopenia (MLT) is a recently described glucose transporter 1-negative multifocal vascular disorder with significant morbidity and mortality. 26148948 1 24 theme multifocal 229:238 arg1 lymphangioendotheliomatosis 118:144 Multifocal lymphangioendotheliomatosis 107:144 Multifocal lymphangioendotheliomatosis with thrombocytopenia (MLT) 107:172 Multifocal lymphangioendotheliomatosis with thrombocytopenia (MLT) is a recently described glucose transporter 1-negative multifocal vascular disorder with significant morbidity and mortality. 26148948 1 24 theme multifocal 229:238 arg1 disorder 249:256 a recently described glucose transporter 1-negative multifocal vascular disorder 177:256 a recently described glucose transporter 1-negative multifocal vascular disorder with significant morbidity and mortality 177:297 Multifocal lymphangioendotheliomatosis with thrombocytopenia (MLT) is a recently described glucose transporter 1-negative multifocal vascular disorder with significant morbidity and mortality. 26148948 3 25 theme infantile 432:440 arg1 hemangioma 442:451 multifocal infantile hemangioma 421:451 multifocal infantile hemangioma 421:451 It is often confused with multifocal infantile hemangioma, but the conditions must be differentiated for appropriate assessment and therapeutic management. 26148948 1 26 theme vascular 240:247 arg1 lymphangioendotheliomatosis 118:144 Multifocal lymphangioendotheliomatosis 107:144 Multifocal lymphangioendotheliomatosis with thrombocytopenia (MLT) 107:172 Multifocal lymphangioendotheliomatosis with thrombocytopenia (MLT) is a recently described glucose transporter 1-negative multifocal vascular disorder with significant morbidity and mortality. 26148948 1 26 theme vascular 240:247 arg1 disorder 249:256 a recently described glucose transporter 1-negative multifocal vascular disorder 177:256 a recently described glucose transporter 1-negative multifocal vascular disorder with significant morbidity and mortality 177:297 Multifocal lymphangioendotheliomatosis with thrombocytopenia (MLT) is a recently described glucose transporter 1-negative multifocal vascular disorder with significant morbidity and mortality. 26148948 5 27 contain had 776:778 arg1 patient 768:774 1 patient 766:774 1 patient 766:774 We report 3 newborn cases featuring various clinical and biological phenotypes of MLT: 1 patient had severe brain involvement and died early; another had no thrombocytopenia; and the third had nearly no skin involvement. 26148948 5 27 contain had 776:778 arg2 involvement 793:803 severe brain involvement 780:803 severe brain involvement 780:803 We report 3 newborn cases featuring various clinical and biological phenotypes of MLT: 1 patient had severe brain involvement and died early; another had no thrombocytopenia; and the third had nearly no skin involvement. 26148948 2 28 theme long-term 352:360 arg1 prognosis 362:370 long-term prognosis 352:370 long-term prognosis 352:370 However, data are lacking on the clinical spectrum, long-term prognosis, and treatment of MLT. 26148948 7 29 with cases 1125:1129 arg1 bleeding 1160:1167 bleeding 1160:1167 bleeding 1160:1167 Two cases with severe gastrointestinal bleeding were treated with sirolimus 0.1 mg/k per day, which was efficient after the first month of treatment. 26148948 1 30 with lymphangioendotheliomatosis 118:144 arg1 MLT 169:171 MLT 169:171 MLT 169:171 Multifocal lymphangioendotheliomatosis with thrombocytopenia (MLT) is a recently described glucose transporter 1-negative multifocal vascular disorder with significant morbidity and mortality. 26148948 1 30 with lymphangioendotheliomatosis 118:144 arg1 thrombocytopenia 151:166 thrombocytopenia 151:166 thrombocytopenia (MLT) 151:172 Multifocal lymphangioendotheliomatosis with thrombocytopenia (MLT) is a recently described glucose transporter 1-negative multifocal vascular disorder with significant morbidity and mortality. 26148948 6 31 theme endothelial 1015:1025 arg1 receptor 1038:1045 endothelial hyaluronan receptor 1 1015:1047 endothelial hyaluronan receptor 1 1015:1047 Histologically, all were negative for glucose transporter 1 and positive for the lymphatic marker lymphatic vessel endothelial hyaluronan receptor 1 or D2-40 (∼38-kDa O-linked transmembrane sialoglycoprotein podoplanin). 26148948 8 32 theme aggressive 1394:1403 arg1 intervention 1417:1428 initial aggressive therapeutic intervention 1386:1428 initial aggressive therapeutic intervention 1386:1428 MLT clinically presents in various forms, and when complicated by widespread or severe extracutaneous involvement, initial aggressive therapeutic intervention is justified. 26148948 5 33 theme skin 882:885 arg1 involvement 887:897 nearly no skin involvement 872:897 nearly no skin involvement 872:897 We report 3 newborn cases featuring various clinical and biological phenotypes of MLT: 1 patient had severe brain involvement and died early; another had no thrombocytopenia; and the third had nearly no skin involvement. 26148948 0 34 theme Clinical 62:69 arg1 Features 71:78 Clinical Features 62:78 Clinical Features 62:78 Multifocal Lymphangioendotheliomatosis With Thrombocytopenia: Clinical Features and Response to Sirolimus. 26148948 1 35 with disorder 249:256 arg1 mortality 289:297 mortality 289:297 mortality 289:297 Multifocal lymphangioendotheliomatosis with thrombocytopenia (MLT) is a recently described glucose transporter 1-negative multifocal vascular disorder with significant morbidity and mortality. 26148948 1 35 with disorder 249:256 arg1 morbidity 275:283 significant morbidity 263:283 significant morbidity 263:283 Multifocal lymphangioendotheliomatosis with thrombocytopenia (MLT) is a recently described glucose transporter 1-negative multifocal vascular disorder with significant morbidity and mortality. 26148948 5 36 contain had 868:870 arg1 third 862:866 third 862:866 third 862:866 We report 3 newborn cases featuring various clinical and biological phenotypes of MLT: 1 patient had severe brain involvement and died early; another had no thrombocytopenia; and the third had nearly no skin involvement. 26148948 5 36 contain had 868:870 arg2 involvement 887:897 nearly no skin involvement 872:897 nearly no skin involvement 872:897 We report 3 newborn cases featuring various clinical and biological phenotypes of MLT: 1 patient had severe brain involvement and died early; another had no thrombocytopenia; and the third had nearly no skin involvement. 26148948 6 37 dep negative 925:932 arg1 D2-40 1052:1056 D2-40 1052:1056 D2-40 (∼38-kDa O-linked transmembrane sialoglycoprotein podoplanin) 1052:1118 Histologically, all were negative for glucose transporter 1 and positive for the lymphatic marker lymphatic vessel endothelial hyaluronan receptor 1 or D2-40 (∼38-kDa O-linked transmembrane sialoglycoprotein podoplanin). 26148948 6 37 dep negative 925:932 arg1 podoplanin 1108:1117 ∼38-kDa O-linked transmembrane sialoglycoprotein podoplanin 1059:1117 ∼38-kDa O-linked transmembrane sialoglycoprotein podoplanin 1059:1117 Histologically, all were negative for glucose transporter 1 and positive for the lymphatic marker lymphatic vessel endothelial hyaluronan receptor 1 or D2-40 (∼38-kDa O-linked transmembrane sialoglycoprotein podoplanin). 26148948 6 37 dep negative 925:932 arg1 receptor 1038:1045 endothelial hyaluronan receptor 1 1015:1047 endothelial hyaluronan receptor 1 1015:1047 Histologically, all were negative for glucose transporter 1 and positive for the lymphatic marker lymphatic vessel endothelial hyaluronan receptor 1 or D2-40 (∼38-kDa O-linked transmembrane sialoglycoprotein podoplanin). 26148948 1 38 theme significant 263:273 arg1 morbidity 275:283 significant morbidity 263:283 significant morbidity 263:283 Multifocal lymphangioendotheliomatosis with thrombocytopenia (MLT) is a recently described glucose transporter 1-negative multifocal vascular disorder with significant morbidity and mortality. 26148948 6 39 theme lymphatic 998:1006 arg1 vessel 1008:1013 the lymphatic marker lymphatic vessel 977:1013 the lymphatic marker lymphatic vessel 977:1013 Histologically, all were negative for glucose transporter 1 and positive for the lymphatic marker lymphatic vessel endothelial hyaluronan receptor 1 or D2-40 (∼38-kDa O-linked transmembrane sialoglycoprotein podoplanin). 26148948 5 40 theme severe 780:785 arg1 involvement 793:803 severe brain involvement 780:803 severe brain involvement 780:803 We report 3 newborn cases featuring various clinical and biological phenotypes of MLT: 1 patient had severe brain involvement and died early; another had no thrombocytopenia; and the third had nearly no skin involvement. 26148948 8 41 theme widespread 1337:1346 arg1 involvement 1373:1383 widespread or severe extracutaneous involvement 1337:1383 widespread or severe extracutaneous involvement 1337:1383 MLT clinically presents in various forms, and when complicated by widespread or severe extracutaneous involvement, initial aggressive therapeutic intervention is justified. 26148948 6 42 theme O-linked 1067:1074 arg1 D2-40 1052:1056 D2-40 1052:1056 D2-40 (∼38-kDa O-linked transmembrane sialoglycoprotein podoplanin) 1052:1118 Histologically, all were negative for glucose transporter 1 and positive for the lymphatic marker lymphatic vessel endothelial hyaluronan receptor 1 or D2-40 (∼38-kDa O-linked transmembrane sialoglycoprotein podoplanin). 26148948 6 42 theme O-linked 1067:1074 arg1 podoplanin 1108:1117 ∼38-kDa O-linked transmembrane sialoglycoprotein podoplanin 1059:1117 ∼38-kDa O-linked transmembrane sialoglycoprotein podoplanin 1059:1117 Histologically, all were negative for glucose transporter 1 and positive for the lymphatic marker lymphatic vessel endothelial hyaluronan receptor 1 or D2-40 (∼38-kDa O-linked transmembrane sialoglycoprotein podoplanin). 26148948 3 43 theme appropriate 500:510 arg1 assessment 512:521 appropriate assessment 500:521 appropriate assessment 500:521 It is often confused with multifocal infantile hemangioma, but the conditions must be differentiated for appropriate assessment and therapeutic management. 26148948 8 44 theme severe 1351:1356 arg1 involvement 1373:1383 widespread or severe extracutaneous involvement 1337:1383 widespread or severe extracutaneous involvement 1337:1383 MLT clinically presents in various forms, and when complicated by widespread or severe extracutaneous involvement, initial aggressive therapeutic intervention is justified. 26148948 6 45 theme marker 991:996 arg1 vessel 1008:1013 the lymphatic marker lymphatic vessel 977:1013 the lymphatic marker lymphatic vessel 977:1013 Histologically, all were negative for glucose transporter 1 and positive for the lymphatic marker lymphatic vessel endothelial hyaluronan receptor 1 or D2-40 (∼38-kDa O-linked transmembrane sialoglycoprotein podoplanin). 26148948 6 46 theme hyaluronan 1027:1036 arg1 receptor 1038:1045 endothelial hyaluronan receptor 1 1015:1047 endothelial hyaluronan receptor 1 1015:1047 Histologically, all were negative for glucose transporter 1 and positive for the lymphatic marker lymphatic vessel endothelial hyaluronan receptor 1 or D2-40 (∼38-kDa O-linked transmembrane sialoglycoprotein podoplanin). 26148948 2 47 theme MLT 390:392 arg1 spectrum 342:349 clinical spectrum 333:349 clinical spectrum 333:349 However, data are lacking on the clinical spectrum, long-term prognosis, and treatment of MLT. 26148948 2 47 theme MLT 390:392 arg1 prognosis 362:370 long-term prognosis 352:370 long-term prognosis 352:370 However, data are lacking on the clinical spectrum, long-term prognosis, and treatment of MLT. 26148948 2 47 theme MLT 390:392 arg1 treatment 377:385 treatment 377:385 treatment 377:385 However, data are lacking on the clinical spectrum, long-term prognosis, and treatment of MLT. 26148948 6 48 theme lymphatic 981:989 arg1 vessel 1008:1013 the lymphatic marker lymphatic vessel 977:1013 the lymphatic marker lymphatic vessel 977:1013 Histologically, all were negative for glucose transporter 1 and positive for the lymphatic marker lymphatic vessel endothelial hyaluronan receptor 1 or D2-40 (∼38-kDa O-linked transmembrane sialoglycoprotein podoplanin). 26148948 10 49 theme adequate 1635:1642 arg1 approach 1669:1676 an adequate and targeted therapeutic approach 1632:1676 an adequate and targeted therapeutic approach for MLT 1632:1684 Because of its antiangiogenic properties, including anti-lymphangiogenesis, sirolimus offers an adequate and targeted therapeutic approach for MLT. 26148948 0 50 with Lymphangioendotheliomatosis 11:37 arg1 Thrombocytopenia 44:59 Thrombocytopenia 44:59 Thrombocytopenia 44:59 Multifocal Lymphangioendotheliomatosis With Thrombocytopenia: Clinical Features and Response to Sirolimus. 26148948 9 51 theme MLT 1464:1466 arg1 pathogenesis 1448:1459 The pathogenesis 1444:1459 The pathogenesis of MLT 1444:1466 The pathogenesis of MLT remains unclear, but lymphatic differentiation is widely acknowledged. 26148948 5 52 theme MLT 761:763 arg1 phenotypes 747:756 various clinical and biological phenotypes 715:756 various clinical and biological phenotypes of MLT 715:763 We report 3 newborn cases featuring various clinical and biological phenotypes of MLT: 1 patient had severe brain involvement and died early; another had no thrombocytopenia; and the third had nearly no skin involvement. 26148948 3 53 theme therapeutic 527:537 arg1 management 539:548 therapeutic management 527:548 therapeutic management 527:548 It is often confused with multifocal infantile hemangioma, but the conditions must be differentiated for appropriate assessment and therapeutic management. 26148948 6 54 theme sialoglycoprotein 1090:1106 arg1 D2-40 1052:1056 D2-40 1052:1056 D2-40 (∼38-kDa O-linked transmembrane sialoglycoprotein podoplanin) 1052:1118 Histologically, all were negative for glucose transporter 1 and positive for the lymphatic marker lymphatic vessel endothelial hyaluronan receptor 1 or D2-40 (∼38-kDa O-linked transmembrane sialoglycoprotein podoplanin). 26148948 6 54 theme sialoglycoprotein 1090:1106 arg1 podoplanin 1108:1117 ∼38-kDa O-linked transmembrane sialoglycoprotein podoplanin 1059:1117 ∼38-kDa O-linked transmembrane sialoglycoprotein podoplanin 1059:1117 Histologically, all were negative for glucose transporter 1 and positive for the lymphatic marker lymphatic vessel endothelial hyaluronan receptor 1 or D2-40 (∼38-kDa O-linked transmembrane sialoglycoprotein podoplanin). 26148948 8 55 theme extracutaneous 1358:1371 arg1 involvement 1373:1383 widespread or severe extracutaneous involvement 1337:1383 widespread or severe extracutaneous involvement 1337:1383 MLT clinically presents in various forms, and when complicated by widespread or severe extracutaneous involvement, initial aggressive therapeutic intervention is justified. 26148948 8 56 theme therapeutic 1405:1415 arg1 intervention 1417:1428 initial aggressive therapeutic intervention 1386:1428 initial aggressive therapeutic intervention 1386:1428 MLT clinically presents in various forms, and when complicated by widespread or severe extracutaneous involvement, initial aggressive therapeutic intervention is justified. 26148948 6 57 theme transmembrane 1076:1088 arg1 D2-40 1052:1056 D2-40 1052:1056 D2-40 (∼38-kDa O-linked transmembrane sialoglycoprotein podoplanin) 1052:1118 Histologically, all were negative for glucose transporter 1 and positive for the lymphatic marker lymphatic vessel endothelial hyaluronan receptor 1 or D2-40 (∼38-kDa O-linked transmembrane sialoglycoprotein podoplanin). 26148948 6 57 theme transmembrane 1076:1088 arg1 podoplanin 1108:1117 ∼38-kDa O-linked transmembrane sialoglycoprotein podoplanin 1059:1117 ∼38-kDa O-linked transmembrane sialoglycoprotein podoplanin 1059:1117 Histologically, all were negative for glucose transporter 1 and positive for the lymphatic marker lymphatic vessel endothelial hyaluronan receptor 1 or D2-40 (∼38-kDa O-linked transmembrane sialoglycoprotein podoplanin). 26148948 0 58 dep Lymphangioendotheliomatosis 11:37 arg1 Response 84:91 Response 84:91 Response to Sirolimus 84:104 Multifocal Lymphangioendotheliomatosis With Thrombocytopenia: Clinical Features and Response to Sirolimus. 26148948 0 58 dep Lymphangioendotheliomatosis 11:37 arg1 Features 71:78 Clinical Features 62:78 Clinical Features 62:78 Multifocal Lymphangioendotheliomatosis With Thrombocytopenia: Clinical Features and Response to Sirolimus. 26148948 6 59 gly sialoglycoprotein 1090:1106 arg1 sialoglycoprotein 1090:1106 ∼38-kDa O-linked transmembrane sialoglycoprotein podoplanin 1059:1117 ∼38-kDa O-linked transmembrane sialoglycoprotein podoplanin 1059:1117 Histologically, all were negative for glucose transporter 1 and positive for the lymphatic marker lymphatic vessel endothelial hyaluronan receptor 1 or D2-40 (∼38-kDa O-linked transmembrane sialoglycoprotein podoplanin). 26148948 8 60 theme initial 1386:1392 arg1 intervention 1417:1428 initial aggressive therapeutic intervention 1386:1428 initial aggressive therapeutic intervention 1386:1428 MLT clinically presents in various forms, and when complicated by widespread or severe extracutaneous involvement, initial aggressive therapeutic intervention is justified. 26148948 8 61 theme various 1298:1304 arg1 forms 1306:1310 various forms 1298:1310 various forms 1298:1310 MLT clinically presents in various forms, and when complicated by widespread or severe extracutaneous involvement, initial aggressive therapeutic intervention is justified. 26148948 5 62 theme biological 736:745 arg1 phenotypes 747:756 various clinical and biological phenotypes 715:756 various clinical and biological phenotypes of MLT 715:763 We report 3 newborn cases featuring various clinical and biological phenotypes of MLT: 1 patient had severe brain involvement and died early; another had no thrombocytopenia; and the third had nearly no skin involvement. 26148948 5 63 contain had 829:831 arg1 another 821:827 another 821:827 another 821:827 We report 3 newborn cases featuring various clinical and biological phenotypes of MLT: 1 patient had severe brain involvement and died early; another had no thrombocytopenia; and the third had nearly no skin involvement. 26148948 5 63 contain had 829:831 arg2 thrombocytopenia 836:851 no thrombocytopenia 833:851 no thrombocytopenia 833:851 We report 3 newborn cases featuring various clinical and biological phenotypes of MLT: 1 patient had severe brain involvement and died early; another had no thrombocytopenia; and the third had nearly no skin involvement. 26148948 7 64 theme first 1245:1249 arg1 month 1251:1255 the first month 1241:1255 the first month of treatment 1241:1268 Two cases with severe gastrointestinal bleeding were treated with sirolimus 0.1 mg/k per day, which was efficient after the first month of treatment. 26148948 6 65 theme ∼38-kDa 1059:1065 arg1 D2-40 1052:1056 D2-40 1052:1056 D2-40 (∼38-kDa O-linked transmembrane sialoglycoprotein podoplanin) 1052:1118 Histologically, all were negative for glucose transporter 1 and positive for the lymphatic marker lymphatic vessel endothelial hyaluronan receptor 1 or D2-40 (∼38-kDa O-linked transmembrane sialoglycoprotein podoplanin). 26148948 6 65 theme ∼38-kDa 1059:1065 arg1 podoplanin 1108:1117 ∼38-kDa O-linked transmembrane sialoglycoprotein podoplanin 1059:1117 ∼38-kDa O-linked transmembrane sialoglycoprotein podoplanin 1059:1117 Histologically, all were negative for glucose transporter 1 and positive for the lymphatic marker lymphatic vessel endothelial hyaluronan receptor 1 or D2-40 (∼38-kDa O-linked transmembrane sialoglycoprotein podoplanin). 25657638 4 0 theme protein 907:913 arg1 expression 915:924 secreted protein expression 898:924 secreted protein expression 898:924 Since adipocytokines levels are regulated primarily at the level of transcription and O-GlcNAc alters the function of many transcription factors, we hypothesized that elevated O-GlcNAc levels on key transcription factors are modulating secreted protein expression. 25657638 0 1 theme Global 0:5 arg1 Levels 16:21 Global O-GlcNAc Levels 0:21 Global O-GlcNAc Levels 0:21 Global O-GlcNAc Levels Modulate Transcription of the Adipocyte Secretome during Chronic Insulin Resistance. 25657638 9 2 theme modified 1677:1684 arg1 proteins 1686:1693 Sp1 and O-GlcNAc modified proteins 1660:1693 Sp1 and O-GlcNAc modified proteins 1660:1693 Furthermore, we show that the LPL and SPARC promoters are enriched for Sp1 and O-GlcNAc modified proteins during insulin resistance in adipocytes. 25657638 6 3 theme diabetes 1204:1211 arg1 models 1194:1199 male mouse models 1183:1199 male mouse models of diabetes 1183:1211 We validate the transcript levels in male mouse models of diabetes. 25657638 10 4 attach linked 1818:1823 arg1 transcription 1842:1854 adipocytokine transcription 1828:1854 adipocytokine transcription 1828:1854 Thus, the O-GlcNAc modification of proteins bound to promoters, including Sp1, is linked to adipocytokine transcription during insulin resistance. 25657638 10 4 attach linked 1818:1823 arg2 modification 1755:1766 the O-GlcNAc modification 1742:1766 the O-GlcNAc modification of proteins bound to promoters, including Sp1, 1742:1813 Thus, the O-GlcNAc modification of proteins bound to promoters, including Sp1, is linked to adipocytokine transcription during insulin resistance. 25657638 3 5 theme relative 596:603 arg1 levels 605:610 the relative levels 592:610 the relative levels of several of these factors 592:638 We have validated the relative levels of several of these factors using immunoblotting. 25657638 1 6 theme proteins 232:239 arg1 glycosylation 215:227 intracellular glycosylation 201:227 intracellular glycosylation of proteins 201:239 Increased flux through the hexosamine biosynthetic pathway and the corresponding increase in intracellular glycosylation of proteins via O-linked β-N-acetylglucosamine (O-GlcNAc) is sufficient to induce insulin resistance (IR) in multiple systems. 25657638 5 7 theme protein 1131:1137 arg1 level 1139:1143 the protein level 1127:1143 the protein level 1127:1143 Here, we show that upon the elevation of O-GlcNAc levels and the induction of IR in mature 3T3-F442a adipocytes, the transcript levels of multiple secreted proteins reflect the modulation observed at the protein level. 25657638 3 8 theme factors 632:638 arg1 several 615:621 several 615:621 several 615:621 We have validated the relative levels of several of these factors using immunoblotting. 25657638 1 9 theme O-linked 245:252 arg1 O-GlcNAc 277:284 O-GlcNAc 277:284 O-GlcNAc 277:284 Increased flux through the hexosamine biosynthetic pathway and the corresponding increase in intracellular glycosylation of proteins via O-linked β-N-acetylglucosamine (O-GlcNAc) is sufficient to induce insulin resistance (IR) in multiple systems. 25657638 1 9 theme O-linked 245:252 arg1 β-N-acetylglucosamine 254:274 O-linked β-N-acetylglucosamine 245:274 O-linked β-N-acetylglucosamine (O-GlcNAc) 245:285 Increased flux through the hexosamine biosynthetic pathway and the corresponding increase in intracellular glycosylation of proteins via O-linked β-N-acetylglucosamine (O-GlcNAc) is sufficient to induce insulin resistance (IR) in multiple systems. 25657638 7 10 theme cell 1402:1405 arg1 culture 1407:1413 cell culture 1402:1413 cell culture 1402:1413 Using inguinal fat pads from the severely IR db/db mouse model and the mildly IR diet-induced mouse model, we have confirmed that the secreted proteins regulated by O-GlcNAc modulation in cell culture are likewise modulated in the whole animal upon a shift to IR. 25657638 5 11 theme O-GlcNAc 968:975 arg1 levels 977:982 O-GlcNAc levels 968:982 O-GlcNAc levels 968:982 Here, we show that upon the elevation of O-GlcNAc levels and the induction of IR in mature 3T3-F442a adipocytes, the transcript levels of multiple secreted proteins reflect the modulation observed at the protein level. 25657638 1 12 theme biosynthetic 146:157 arg1 pathway 159:165 the hexosamine biosynthetic pathway 131:165 the hexosamine biosynthetic pathway 131:165 Increased flux through the hexosamine biosynthetic pathway and the corresponding increase in intracellular glycosylation of proteins via O-linked β-N-acetylglucosamine (O-GlcNAc) is sufficient to induce insulin resistance (IR) in multiple systems. 25657638 5 13 theme levels 977:982 arg1 elevation 955:963 the elevation 951:963 the elevation of O-GlcNAc levels 951:982 Here, we show that upon the elevation of O-GlcNAc levels and the induction of IR in mature 3T3-F442a adipocytes, the transcript levels of multiple secreted proteins reflect the modulation observed at the protein level. 25657638 5 13 theme levels 977:982 arg1 induction 992:1000 the induction 988:1000 the induction of IR in mature 3T3-F442a adipocytes 988:1037 Here, we show that upon the elevation of O-GlcNAc levels and the induction of IR in mature 3T3-F442a adipocytes, the transcript levels of multiple secreted proteins reflect the modulation observed at the protein level. 25657638 7 14 from model 1271:1275 arg1 pads 1233:1236 inguinal fat pads 1220:1236 inguinal fat pads from the severely IR db/db mouse model and the mildly IR diet-induced mouse model 1220:1318 Using inguinal fat pads from the severely IR db/db mouse model and the mildly IR diet-induced mouse model, we have confirmed that the secreted proteins regulated by O-GlcNAc modulation in cell culture are likewise modulated in the whole animal upon a shift to IR. 25657638 4 15 theme transcription 730:742 arg1 level 721:725 the level 717:725 the level of transcription and O-GlcNAc alters the function of many transcription factors 717:805 Since adipocytokines levels are regulated primarily at the level of transcription and O-GlcNAc alters the function of many transcription factors, we hypothesized that elevated O-GlcNAc levels on key transcription factors are modulating secreted protein expression. 25657638 0 16 theme Secretome 63:71 arg1 Transcription 32:44 Transcription 32:44 Transcription of the Adipocyte Secretome 32:71 Global O-GlcNAc Levels Modulate Transcription of the Adipocyte Secretome during Chronic Insulin Resistance. 25657638 4 17 from levels 847:852 arg1 factors 875:881 key transcription factors 857:881 key transcription factors 857:881 Since adipocytokines levels are regulated primarily at the level of transcription and O-GlcNAc alters the function of many transcription factors, we hypothesized that elevated O-GlcNAc levels on key transcription factors are modulating secreted protein expression. 25657638 4 18 theme O-GlcNAc 748:755 arg1 level 721:725 the level 717:725 the level of transcription and O-GlcNAc alters the function of many transcription factors 717:805 Since adipocytokines levels are regulated primarily at the level of transcription and O-GlcNAc alters the function of many transcription factors, we hypothesized that elevated O-GlcNAc levels on key transcription factors are modulating secreted protein expression. 25657638 0 19 theme Chronic 80:86 arg1 Resistance 96:105 Chronic Insulin Resistance 80:105 Chronic Insulin Resistance 80:105 Global O-GlcNAc Levels Modulate Transcription of the Adipocyte Secretome during Chronic Insulin Resistance. 25657638 1 20 theme corresponding 175:187 arg1 sufficient 290:299 sufficient 290:299 sufficient 290:299 Increased flux through the hexosamine biosynthetic pathway and the corresponding increase in intracellular glycosylation of proteins via O-linked β-N-acetylglucosamine (O-GlcNAc) is sufficient to induce insulin resistance (IR) in multiple systems. 25657638 1 20 theme corresponding 175:187 arg1 increase 189:196 the corresponding increase 171:196 the corresponding increase in intracellular glycosylation of proteins 171:239 Increased flux through the hexosamine biosynthetic pathway and the corresponding increase in intracellular glycosylation of proteins via O-linked β-N-acetylglucosamine (O-GlcNAc) is sufficient to induce insulin resistance (IR) in multiple systems. 25657638 8 21 theme genes 1528:1532 arg1 promoters 1495:1503 the promoters 1491:1503 the promoters of similarly regulated genes 1491:1532 By comparing the promoters of similarly regulated genes, we determine that Sp1 is a common cis-acting element. 25657638 2 22 used used 378:381 arg2 group 372:376 our group 368:376 our group 368:376 Previously, our group used shotgun proteomics to identify multiple rodent adipocytokines and secreted proteins whose levels are modulated upon the induction of IR by indirectly and directly modulating O-GlcNAc levels. 25657638 5 23 theme mature 1011:1016 arg1 adipocytes 1028:1037 mature 3T3-F442a adipocytes 1011:1037 mature 3T3-F442a adipocytes 1011:1037 Here, we show that upon the elevation of O-GlcNAc levels and the induction of IR in mature 3T3-F442a adipocytes, the transcript levels of multiple secreted proteins reflect the modulation observed at the protein level. 25657638 4 24 theme elevated 829:836 arg1 levels 847:852 elevated O-GlcNAc levels 829:852 elevated O-GlcNAc levels on key transcription factors 829:881 Since adipocytokines levels are regulated primarily at the level of transcription and O-GlcNAc alters the function of many transcription factors, we hypothesized that elevated O-GlcNAc levels on key transcription factors are modulating secreted protein expression. 25657638 2 25 theme rodent 423:428 arg1 adipocytokines 430:443 multiple rodent adipocytokines 414:443 multiple rodent adipocytokines 414:443 Previously, our group used shotgun proteomics to identify multiple rodent adipocytokines and secreted proteins whose levels are modulated upon the induction of IR by indirectly and directly modulating O-GlcNAc levels. 25657638 4 26 theme transcription 785:797 arg1 factors 799:805 many transcription factors 780:805 many transcription factors 780:805 Since adipocytokines levels are regulated primarily at the level of transcription and O-GlcNAc alters the function of many transcription factors, we hypothesized that elevated O-GlcNAc levels on key transcription factors are modulating secreted protein expression. 25657638 7 27 theme fat 1229:1231 arg1 pads 1233:1236 inguinal fat pads 1220:1236 inguinal fat pads from the severely IR db/db mouse model and the mildly IR diet-induced mouse model 1220:1318 Using inguinal fat pads from the severely IR db/db mouse model and the mildly IR diet-induced mouse model, we have confirmed that the secreted proteins regulated by O-GlcNAc modulation in cell culture are likewise modulated in the whole animal upon a shift to IR. 25657638 1 28 theme insulin 311:317 arg1 IR 331:332 IR 331:332 IR 331:332 Increased flux through the hexosamine biosynthetic pathway and the corresponding increase in intracellular glycosylation of proteins via O-linked β-N-acetylglucosamine (O-GlcNAc) is sufficient to induce insulin resistance (IR) in multiple systems. 25657638 1 28 theme insulin 311:317 arg1 resistance 319:328 insulin resistance 311:328 insulin resistance (IR) 311:333 Increased flux through the hexosamine biosynthetic pathway and the corresponding increase in intracellular glycosylation of proteins via O-linked β-N-acetylglucosamine (O-GlcNAc) is sufficient to induce insulin resistance (IR) in multiple systems. 25657638 7 29 theme secreted 1348:1355 arg1 proteins 1357:1364 the secreted proteins 1344:1364 the secreted proteins regulated by O-GlcNAc modulation in cell culture 1344:1413 Using inguinal fat pads from the severely IR db/db mouse model and the mildly IR diet-induced mouse model, we have confirmed that the secreted proteins regulated by O-GlcNAc modulation in cell culture are likewise modulated in the whole animal upon a shift to IR. 25657638 5 30 theme IR 1005:1006 arg1 elevation 955:963 the elevation 951:963 the elevation of O-GlcNAc levels 951:982 Here, we show that upon the elevation of O-GlcNAc levels and the induction of IR in mature 3T3-F442a adipocytes, the transcript levels of multiple secreted proteins reflect the modulation observed at the protein level. 25657638 5 30 theme IR 1005:1006 arg1 induction 992:1000 the induction 988:1000 the induction of IR in mature 3T3-F442a adipocytes 988:1037 Here, we show that upon the elevation of O-GlcNAc levels and the induction of IR in mature 3T3-F442a adipocytes, the transcript levels of multiple secreted proteins reflect the modulation observed at the protein level. 25657638 8 31 theme common 1562:1567 arg1 element 1580:1586 a common cis-acting element 1560:1586 a common cis-acting element 1560:1586 By comparing the promoters of similarly regulated genes, we determine that Sp1 is a common cis-acting element. 25657638 8 31 theme common 1562:1567 arg1 Sp1 1553:1555 Sp1 1553:1555 Sp1 1553:1555 By comparing the promoters of similarly regulated genes, we determine that Sp1 is a common cis-acting element. 25657638 10 32 theme insulin 1863:1869 arg1 resistance 1871:1880 insulin resistance 1863:1880 insulin resistance 1863:1880 Thus, the O-GlcNAc modification of proteins bound to promoters, including Sp1, is linked to adipocytokine transcription during insulin resistance. 25657638 5 33 theme multiple 1065:1072 arg1 proteins 1083:1090 multiple secreted proteins 1065:1090 multiple secreted proteins 1065:1090 Here, we show that upon the elevation of O-GlcNAc levels and the induction of IR in mature 3T3-F442a adipocytes, the transcript levels of multiple secreted proteins reflect the modulation observed at the protein level. 25657638 1 34 theme multiple 338:345 arg1 systems 347:353 multiple systems 338:353 multiple systems 338:353 Increased flux through the hexosamine biosynthetic pathway and the corresponding increase in intracellular glycosylation of proteins via O-linked β-N-acetylglucosamine (O-GlcNAc) is sufficient to induce insulin resistance (IR) in multiple systems. 25657638 9 35 theme O-GlcNAc 1668:1675 arg1 proteins 1686:1693 Sp1 and O-GlcNAc modified proteins 1660:1693 Sp1 and O-GlcNAc modified proteins 1660:1693 Furthermore, we show that the LPL and SPARC promoters are enriched for Sp1 and O-GlcNAc modified proteins during insulin resistance in adipocytes. 25657638 1 36 from flux 118:121 arg1 glycosylation 215:227 intracellular glycosylation 201:227 intracellular glycosylation of proteins 201:239 Increased flux through the hexosamine biosynthetic pathway and the corresponding increase in intracellular glycosylation of proteins via O-linked β-N-acetylglucosamine (O-GlcNAc) is sufficient to induce insulin resistance (IR) in multiple systems. 25657638 6 37 theme transcript 1162:1171 arg1 levels 1173:1178 the transcript levels 1158:1178 the transcript levels in male mouse models of diabetes 1158:1211 We validate the transcript levels in male mouse models of diabetes. 25657638 4 38 theme key 857:859 arg1 factors 875:881 key transcription factors 857:881 key transcription factors 857:881 Since adipocytokines levels are regulated primarily at the level of transcription and O-GlcNAc alters the function of many transcription factors, we hypothesized that elevated O-GlcNAc levels on key transcription factors are modulating secreted protein expression. 25657638 5 39 from induction 992:1000 arg1 adipocytes 1028:1037 mature 3T3-F442a adipocytes 1011:1037 mature 3T3-F442a adipocytes 1011:1037 Here, we show that upon the elevation of O-GlcNAc levels and the induction of IR in mature 3T3-F442a adipocytes, the transcript levels of multiple secreted proteins reflect the modulation observed at the protein level. 25657638 7 40 theme IR 1292:1293 arg1 model 1314:1318 the mildly IR diet-induced mouse model 1281:1318 the mildly IR diet-induced mouse model 1281:1318 Using inguinal fat pads from the severely IR db/db mouse model and the mildly IR diet-induced mouse model, we have confirmed that the secreted proteins regulated by O-GlcNAc modulation in cell culture are likewise modulated in the whole animal upon a shift to IR. 25657638 7 41 theme IR 1256:1257 arg1 model 1271:1275 the severely IR db/db mouse model 1243:1275 the severely IR db/db mouse model 1243:1275 Using inguinal fat pads from the severely IR db/db mouse model and the mildly IR diet-induced mouse model, we have confirmed that the secreted proteins regulated by O-GlcNAc modulation in cell culture are likewise modulated in the whole animal upon a shift to IR. 25657638 1 42 gly glycosylation 215:227 arg1 proteins 232:239 proteins 232:239 proteins 232:239 Increased flux through the hexosamine biosynthetic pathway and the corresponding increase in intracellular glycosylation of proteins via O-linked β-N-acetylglucosamine (O-GlcNAc) is sufficient to induce insulin resistance (IR) in multiple systems. 25657638 1 43 from increase 189:196 arg1 glycosylation 215:227 intracellular glycosylation 201:227 intracellular glycosylation of proteins 201:239 Increased flux through the hexosamine biosynthetic pathway and the corresponding increase in intracellular glycosylation of proteins via O-linked β-N-acetylglucosamine (O-GlcNAc) is sufficient to induce insulin resistance (IR) in multiple systems. 25657638 9 44 theme Sp1 1660:1662 arg1 proteins 1686:1693 Sp1 and O-GlcNAc modified proteins 1660:1693 Sp1 and O-GlcNAc modified proteins 1660:1693 Furthermore, we show that the LPL and SPARC promoters are enriched for Sp1 and O-GlcNAc modified proteins during insulin resistance in adipocytes. 25657638 10 45 theme O-GlcNAc 1746:1753 arg1 modification 1755:1766 the O-GlcNAc modification 1742:1766 the O-GlcNAc modification of proteins bound to promoters, including Sp1, 1742:1813 Thus, the O-GlcNAc modification of proteins bound to promoters, including Sp1, is linked to adipocytokine transcription during insulin resistance. 25657638 4 46 theme secreted 898:905 arg1 expression 915:924 secreted protein expression 898:924 secreted protein expression 898:924 Since adipocytokines levels are regulated primarily at the level of transcription and O-GlcNAc alters the function of many transcription factors, we hypothesized that elevated O-GlcNAc levels on key transcription factors are modulating secreted protein expression. 25657638 7 47 theme db/db 1259:1263 arg1 model 1271:1275 the severely IR db/db mouse model 1243:1275 the severely IR db/db mouse model 1243:1275 Using inguinal fat pads from the severely IR db/db mouse model and the mildly IR diet-induced mouse model, we have confirmed that the secreted proteins regulated by O-GlcNAc modulation in cell culture are likewise modulated in the whole animal upon a shift to IR. 25657638 1 48 theme intracellular 201:213 arg1 glycosylation 215:227 intracellular glycosylation 201:227 intracellular glycosylation of proteins 201:239 Increased flux through the hexosamine biosynthetic pathway and the corresponding increase in intracellular glycosylation of proteins via O-linked β-N-acetylglucosamine (O-GlcNAc) is sufficient to induce insulin resistance (IR) in multiple systems. 25657638 7 49 from model 1314:1318 arg1 pads 1233:1236 inguinal fat pads 1220:1236 inguinal fat pads from the severely IR db/db mouse model and the mildly IR diet-induced mouse model 1220:1318 Using inguinal fat pads from the severely IR db/db mouse model and the mildly IR diet-induced mouse model, we have confirmed that the secreted proteins regulated by O-GlcNAc modulation in cell culture are likewise modulated in the whole animal upon a shift to IR. 25657638 7 50 theme whole 1445:1449 arg1 animal 1451:1456 the whole animal 1441:1456 the whole animal 1441:1456 Using inguinal fat pads from the severely IR db/db mouse model and the mildly IR diet-induced mouse model, we have confirmed that the secreted proteins regulated by O-GlcNAc modulation in cell culture are likewise modulated in the whole animal upon a shift to IR. 25657638 5 51 theme proteins 1083:1090 arg1 levels 1055:1060 the transcript levels 1040:1060 the transcript levels of multiple secreted proteins 1040:1090 Here, we show that upon the elevation of O-GlcNAc levels and the induction of IR in mature 3T3-F442a adipocytes, the transcript levels of multiple secreted proteins reflect the modulation observed at the protein level. 25657638 9 52 theme insulin 1702:1708 arg1 resistance 1710:1719 insulin resistance 1702:1719 insulin resistance in adipocytes 1702:1733 Furthermore, we show that the LPL and SPARC promoters are enriched for Sp1 and O-GlcNAc modified proteins during insulin resistance in adipocytes. 25657638 6 53 theme mouse 1188:1192 arg1 models 1194:1199 male mouse models 1183:1199 male mouse models of diabetes 1183:1211 We validate the transcript levels in male mouse models of diabetes. 25657638 4 54 theme adipocytokines 668:681 arg1 levels 683:688 adipocytokines levels 668:688 adipocytokines levels 668:688 Since adipocytokines levels are regulated primarily at the level of transcription and O-GlcNAc alters the function of many transcription factors, we hypothesized that elevated O-GlcNAc levels on key transcription factors are modulating secreted protein expression. 25657638 5 55 located observed 1115:1122 arg2 modulation 1104:1113 the modulation 1100:1113 the modulation observed at the protein level 1100:1143 Here, we show that upon the elevation of O-GlcNAc levels and the induction of IR in mature 3T3-F442a adipocytes, the transcript levels of multiple secreted proteins reflect the modulation observed at the protein level. 25657638 5 55 located observed 1115:1122 arg1 level 1139:1143 the protein level 1127:1143 the protein level 1127:1143 Here, we show that upon the elevation of O-GlcNAc levels and the induction of IR in mature 3T3-F442a adipocytes, the transcript levels of multiple secreted proteins reflect the modulation observed at the protein level. 25657638 3 56 theme several 615:621 arg1 levels 605:610 the relative levels 592:610 the relative levels of several of these factors 592:638 We have validated the relative levels of several of these factors using immunoblotting. 25657638 4 57 dep level 721:725 arg1 alters 757:762 alters 757:762 alters the function of many transcription factors 757:805 Since adipocytokines levels are regulated primarily at the level of transcription and O-GlcNAc alters the function of many transcription factors, we hypothesized that elevated O-GlcNAc levels on key transcription factors are modulating secreted protein expression. 25657638 10 58 theme adipocytokine 1828:1840 arg1 transcription 1842:1854 adipocytokine transcription 1828:1854 adipocytokine transcription 1828:1854 Thus, the O-GlcNAc modification of proteins bound to promoters, including Sp1, is linked to adipocytokine transcription during insulin resistance. 25657638 1 59 theme hexosamine 135:144 arg1 pathway 159:165 the hexosamine biosynthetic pathway 131:165 the hexosamine biosynthetic pathway 131:165 Increased flux through the hexosamine biosynthetic pathway and the corresponding increase in intracellular glycosylation of proteins via O-linked β-N-acetylglucosamine (O-GlcNAc) is sufficient to induce insulin resistance (IR) in multiple systems. 25657638 7 60 theme mouse 1265:1269 arg1 model 1271:1275 the severely IR db/db mouse model 1243:1275 the severely IR db/db mouse model 1243:1275 Using inguinal fat pads from the severely IR db/db mouse model and the mildly IR diet-induced mouse model, we have confirmed that the secreted proteins regulated by O-GlcNAc modulation in cell culture are likewise modulated in the whole animal upon a shift to IR. 25657638 8 61 theme regulated 1518:1526 arg1 genes 1528:1532 similarly regulated genes 1508:1532 similarly regulated genes 1508:1532 By comparing the promoters of similarly regulated genes, we determine that Sp1 is a common cis-acting element. 25657638 7 62 theme O-GlcNAc 1379:1386 arg1 modulation 1388:1397 O-GlcNAc modulation 1379:1397 O-GlcNAc modulation 1379:1397 Using inguinal fat pads from the severely IR db/db mouse model and the mildly IR diet-induced mouse model, we have confirmed that the secreted proteins regulated by O-GlcNAc modulation in cell culture are likewise modulated in the whole animal upon a shift to IR. 25657638 0 63 theme Insulin 88:94 arg1 Resistance 96:105 Chronic Insulin Resistance 80:105 Chronic Insulin Resistance 80:105 Global O-GlcNAc Levels Modulate Transcription of the Adipocyte Secretome during Chronic Insulin Resistance. 25657638 9 64 from resistance 1710:1719 arg1 adipocytes 1724:1733 adipocytes 1724:1733 adipocytes 1724:1733 Furthermore, we show that the LPL and SPARC promoters are enriched for Sp1 and O-GlcNAc modified proteins during insulin resistance in adipocytes. 25657638 2 65 theme IR 516:517 arg1 induction 503:511 the induction 499:511 the induction of IR 499:517 Previously, our group used shotgun proteomics to identify multiple rodent adipocytokines and secreted proteins whose levels are modulated upon the induction of IR by indirectly and directly modulating O-GlcNAc levels. 25657638 1 66 link O-linked 245:252 arg1 O-GlcNAc 277:284 O-GlcNAc 277:284 O-GlcNAc 277:284 Increased flux through the hexosamine biosynthetic pathway and the corresponding increase in intracellular glycosylation of proteins via O-linked β-N-acetylglucosamine (O-GlcNAc) is sufficient to induce insulin resistance (IR) in multiple systems. 25657638 1 66 link O-linked 245:252 arg1 β-N-acetylglucosamine 254:274 O-linked β-N-acetylglucosamine 245:274 O-linked β-N-acetylglucosamine (O-GlcNAc) 245:285 Increased flux through the hexosamine biosynthetic pathway and the corresponding increase in intracellular glycosylation of proteins via O-linked β-N-acetylglucosamine (O-GlcNAc) is sufficient to induce insulin resistance (IR) in multiple systems. 25657638 5 67 from elevation 955:963 arg1 adipocytes 1028:1037 mature 3T3-F442a adipocytes 1011:1037 mature 3T3-F442a adipocytes 1011:1037 Here, we show that upon the elevation of O-GlcNAc levels and the induction of IR in mature 3T3-F442a adipocytes, the transcript levels of multiple secreted proteins reflect the modulation observed at the protein level. 25657638 10 68 theme proteins 1771:1778 arg1 modification 1755:1766 the O-GlcNAc modification 1742:1766 the O-GlcNAc modification of proteins bound to promoters, including Sp1, 1742:1813 Thus, the O-GlcNAc modification of proteins bound to promoters, including Sp1, is linked to adipocytokine transcription during insulin resistance. 25657638 2 69 theme O-GlcNAc 557:564 arg1 levels 566:571 O-GlcNAc levels 557:571 O-GlcNAc levels 557:571 Previously, our group used shotgun proteomics to identify multiple rodent adipocytokines and secreted proteins whose levels are modulated upon the induction of IR by indirectly and directly modulating O-GlcNAc levels. 25657638 7 70 theme mouse 1308:1312 arg1 model 1314:1318 the mildly IR diet-induced mouse model 1281:1318 the mildly IR diet-induced mouse model 1281:1318 Using inguinal fat pads from the severely IR db/db mouse model and the mildly IR diet-induced mouse model, we have confirmed that the secreted proteins regulated by O-GlcNAc modulation in cell culture are likewise modulated in the whole animal upon a shift to IR. 25657638 5 71 theme 3T3-F442a 1018:1026 arg1 adipocytes 1028:1037 mature 3T3-F442a adipocytes 1011:1037 mature 3T3-F442a adipocytes 1011:1037 Here, we show that upon the elevation of O-GlcNAc levels and the induction of IR in mature 3T3-F442a adipocytes, the transcript levels of multiple secreted proteins reflect the modulation observed at the protein level. 25657638 2 72 theme multiple 414:421 arg1 adipocytokines 430:443 multiple rodent adipocytokines 414:443 multiple rodent adipocytokines 414:443 Previously, our group used shotgun proteomics to identify multiple rodent adipocytokines and secreted proteins whose levels are modulated upon the induction of IR by indirectly and directly modulating O-GlcNAc levels. 25657638 0 73 theme O-GlcNAc 7:14 arg1 Levels 16:21 Global O-GlcNAc Levels 0:21 Global O-GlcNAc Levels 0:21 Global O-GlcNAc Levels Modulate Transcription of the Adipocyte Secretome during Chronic Insulin Resistance. 25657638 4 74 theme many 780:783 arg1 factors 799:805 many transcription factors 780:805 many transcription factors 780:805 Since adipocytokines levels are regulated primarily at the level of transcription and O-GlcNAc alters the function of many transcription factors, we hypothesized that elevated O-GlcNAc levels on key transcription factors are modulating secreted protein expression. 25657638 9 75 theme SPARC 1627:1631 arg1 promoters 1633:1641 the LPL and SPARC promoters 1615:1641 the LPL and SPARC promoters 1615:1641 Furthermore, we show that the LPL and SPARC promoters are enriched for Sp1 and O-GlcNAc modified proteins during insulin resistance in adipocytes. 25657638 1 76 theme Increased 108:116 arg1 flux 118:121 Increased flux 108:121 Increased flux through the hexosamine biosynthetic pathway 108:165 Increased flux through the hexosamine biosynthetic pathway and the corresponding increase in intracellular glycosylation of proteins via O-linked β-N-acetylglucosamine (O-GlcNAc) is sufficient to induce insulin resistance (IR) in multiple systems. 25657638 8 77 theme cis-acting 1569:1578 arg1 element 1580:1586 a common cis-acting element 1560:1586 a common cis-acting element 1560:1586 By comparing the promoters of similarly regulated genes, we determine that Sp1 is a common cis-acting element. 25657638 8 77 theme cis-acting 1569:1578 arg1 Sp1 1553:1555 Sp1 1553:1555 Sp1 1553:1555 By comparing the promoters of similarly regulated genes, we determine that Sp1 is a common cis-acting element. 25657638 4 78 theme factors 799:805 arg1 function 768:775 the function 764:775 the function of many transcription factors 764:805 Since adipocytokines levels are regulated primarily at the level of transcription and O-GlcNAc alters the function of many transcription factors, we hypothesized that elevated O-GlcNAc levels on key transcription factors are modulating secreted protein expression. 25657638 2 79 theme secreted 449:456 arg1 proteins 458:465 secreted proteins 449:465 secreted proteins 449:465 Previously, our group used shotgun proteomics to identify multiple rodent adipocytokines and secreted proteins whose levels are modulated upon the induction of IR by indirectly and directly modulating O-GlcNAc levels. 25657638 4 80 theme transcription 861:873 arg1 factors 875:881 key transcription factors 857:881 key transcription factors 857:881 Since adipocytokines levels are regulated primarily at the level of transcription and O-GlcNAc alters the function of many transcription factors, we hypothesized that elevated O-GlcNAc levels on key transcription factors are modulating secreted protein expression. 25657638 6 81 from levels 1173:1178 arg1 models 1194:1199 male mouse models 1183:1199 male mouse models of diabetes 1183:1211 We validate the transcript levels in male mouse models of diabetes. 25657638 0 82 theme Adipocyte 53:61 arg1 Secretome 63:71 the Adipocyte Secretome 49:71 the Adipocyte Secretome 49:71 Global O-GlcNAc Levels Modulate Transcription of the Adipocyte Secretome during Chronic Insulin Resistance. 25657638 5 83 theme secreted 1074:1081 arg1 proteins 1083:1090 multiple secreted proteins 1065:1090 multiple secreted proteins 1065:1090 Here, we show that upon the elevation of O-GlcNAc levels and the induction of IR in mature 3T3-F442a adipocytes, the transcript levels of multiple secreted proteins reflect the modulation observed at the protein level. 25657638 6 84 theme male 1183:1186 arg1 models 1194:1199 male mouse models 1183:1199 male mouse models of diabetes 1183:1211 We validate the transcript levels in male mouse models of diabetes. 25657638 9 85 theme LPL 1619:1621 arg1 promoters 1633:1641 the LPL and SPARC promoters 1615:1641 the LPL and SPARC promoters 1615:1641 Furthermore, we show that the LPL and SPARC promoters are enriched for Sp1 and O-GlcNAc modified proteins during insulin resistance in adipocytes. 25657638 7 86 theme diet-induced 1295:1306 arg1 model 1314:1318 the mildly IR diet-induced mouse model 1281:1318 the mildly IR diet-induced mouse model 1281:1318 Using inguinal fat pads from the severely IR db/db mouse model and the mildly IR diet-induced mouse model, we have confirmed that the secreted proteins regulated by O-GlcNAc modulation in cell culture are likewise modulated in the whole animal upon a shift to IR. 25657638 4 87 theme O-GlcNAc 838:845 arg1 levels 847:852 elevated O-GlcNAc levels 829:852 elevated O-GlcNAc levels on key transcription factors 829:881 Since adipocytokines levels are regulated primarily at the level of transcription and O-GlcNAc alters the function of many transcription factors, we hypothesized that elevated O-GlcNAc levels on key transcription factors are modulating secreted protein expression. 25657638 2 88 theme shotgun 383:389 arg1 proteomics 391:400 shotgun proteomics 383:400 shotgun proteomics 383:400 Previously, our group used shotgun proteomics to identify multiple rodent adipocytokines and secreted proteins whose levels are modulated upon the induction of IR by indirectly and directly modulating O-GlcNAc levels. 25657638 5 89 theme transcript 1044:1053 arg1 levels 1055:1060 the transcript levels 1040:1060 the transcript levels of multiple secreted proteins 1040:1090 Here, we show that upon the elevation of O-GlcNAc levels and the induction of IR in mature 3T3-F442a adipocytes, the transcript levels of multiple secreted proteins reflect the modulation observed at the protein level. 25657638 7 90 theme inguinal 1220:1227 arg1 pads 1233:1236 inguinal fat pads 1220:1236 inguinal fat pads from the severely IR db/db mouse model and the mildly IR diet-induced mouse model 1220:1318 Using inguinal fat pads from the severely IR db/db mouse model and the mildly IR diet-induced mouse model, we have confirmed that the secreted proteins regulated by O-GlcNAc modulation in cell culture are likewise modulated in the whole animal upon a shift to IR. 24418849 7 0 theme novel 1172:1176 arg1 modifications 1218:1230 novel and diverse pannexin post-translational modifications 1172:1230 novel and diverse pannexin post-translational modifications suggesting that they may be differentially regulated for distinct or overlapping cellular and physiological functions 1172:1348 Taken together, our findings uncover novel and diverse pannexin post-translational modifications suggesting that they may be differentially regulated for distinct or overlapping cellular and physiological functions. 24418849 2 1 theme release 358:364 arg1 channels 366:373 ATP release channels 354:373 ATP release channels 354:373 Pannexins have been implicated in many physiological processes as well as pathological conditions, primarily through their function as ATP release channels. 24418849 1 2 theme related 171:177 arg1 members 179:185 3 distinct but related members 156:185 3 distinct but related members called Panx1, Panx2, and Panx3 156:216 The pannexin family of channel-forming proteins is composed of 3 distinct but related members called Panx1, Panx2, and Panx3. 24418849 4 3 from pannexins 613:621 arg1 cells 635:639 HEK-293T cells 626:639 HEK-293T cells 626:639 Using in vitro biochemical assays performed on ectopically expressed pannexins in HEK-293T cells, we confirmed that all 3 pannexins are N-glycosylated to different degrees, but they are not modified by sialylation or O-linked glycosylation in a manner that changes their apparent molecular weight. 24418849 2 4 theme ATP 354:356 arg1 channels 366:373 ATP release channels 354:373 ATP release channels 354:373 Pannexins have been implicated in many physiological processes as well as pathological conditions, primarily through their function as ATP release channels. 24418849 2 5 theme pathological 293:304 arg1 conditions 306:315 pathological conditions 293:315 many physiological processes as well as pathological conditions 253:315 Pannexins have been implicated in many physiological processes as well as pathological conditions, primarily through their function as ATP release channels. 24418849 5 6 theme Panx2 934:938 arg1 substrate 945:953 a substrate 943:953 a substrate for caspase cleavage 943:974 Using cell-free caspase assays, we also discovered that similar to Panx1, the C-terminus of Panx2 is a substrate for caspase cleavage. 24418849 5 6 theme Panx2 934:938 arg1 C-terminus 920:929 the C-terminus 916:929 the C-terminus of Panx2 916:938 Using cell-free caspase assays, we also discovered that similar to Panx1, the C-terminus of Panx2 is a substrate for caspase cleavage. 24418849 4 7 gly N-glycosylated 680:693 arg1 pannexins 666:674 all 3 pannexins 660:674 all 3 pannexins 660:674 Using in vitro biochemical assays performed on ectopically expressed pannexins in HEK-293T cells, we confirmed that all 3 pannexins are N-glycosylated to different degrees, but they are not modified by sialylation or O-linked glycosylation in a manner that changes their apparent molecular weight. 24418849 4 8 mod modified 734:741 arg1 they 721:724 they 721:724 they 721:724 Using in vitro biochemical assays performed on ectopically expressed pannexins in HEK-293T cells, we confirmed that all 3 pannexins are N-glycosylated to different degrees, but they are not modified by sialylation or O-linked glycosylation in a manner that changes their apparent molecular weight. 24418849 4 8 mod modified 734:741 arg3 sialylation 746:756 sialylation 746:756 sialylation 746:756 Using in vitro biochemical assays performed on ectopically expressed pannexins in HEK-293T cells, we confirmed that all 3 pannexins are N-glycosylated to different degrees, but they are not modified by sialylation or O-linked glycosylation in a manner that changes their apparent molecular weight. 24418849 4 8 mod modified 734:741 arg3 glycosylation 770:782 O-linked glycosylation 761:782 O-linked glycosylation 761:782 Using in vitro biochemical assays performed on ectopically expressed pannexins in HEK-293T cells, we confirmed that all 3 pannexins are N-glycosylated to different degrees, but they are not modified by sialylation or O-linked glycosylation in a manner that changes their apparent molecular weight. 24418849 4 9 theme O-linked 761:768 arg1 glycosylation 770:782 O-linked glycosylation 761:782 O-linked glycosylation 761:782 Using in vitro biochemical assays performed on ectopically expressed pannexins in HEK-293T cells, we confirmed that all 3 pannexins are N-glycosylated to different degrees, but they are not modified by sialylation or O-linked glycosylation in a manner that changes their apparent molecular weight. 24418849 4 10 theme expressed 603:611 arg1 pannexins 613:621 ectopically expressed pannexins 591:621 ectopically expressed pannexins in HEK-293T cells 591:639 Using in vitro biochemical assays performed on ectopically expressed pannexins in HEK-293T cells, we confirmed that all 3 pannexins are N-glycosylated to different degrees, but they are not modified by sialylation or O-linked glycosylation in a manner that changes their apparent molecular weight. 24418849 1 11 theme proteins 132:139 arg1 family 106:111 The pannexin family 93:111 The pannexin family of channel-forming proteins 93:139 The pannexin family of channel-forming proteins is composed of 3 distinct but related members called Panx1, Panx2, and Panx3. 24418849 6 12 theme biotin 1055:1060 arg1 assay 1069:1073 an in vitro biotin switch assay 1043:1073 an in vitro biotin switch assay 1043:1073 Panx3, on the other hand, is not subject to caspase digestion but an in vitro biotin switch assay revealed that it was S-nitrosylated by nitric oxide donors. 24418849 5 13 theme cell-free 848:856 arg1 assays 866:871 cell-free caspase assays 848:871 cell-free caspase assays 848:871 Using cell-free caspase assays, we also discovered that similar to Panx1, the C-terminus of Panx2 is a substrate for caspase cleavage. 24418849 6 14 theme in 1046:1047 arg1 assay 1069:1073 an in vitro biotin switch assay 1043:1073 an in vitro biotin switch assay 1043:1073 Panx3, on the other hand, is not subject to caspase digestion but an in vitro biotin switch assay revealed that it was S-nitrosylated by nitric oxide donors. 24418849 6 15 from Panx3 977:981 arg1 hand 997:1000 the other hand 987:1000 the other hand 987:1000 Panx3, on the other hand, is not subject to caspase digestion but an in vitro biotin switch assay revealed that it was S-nitrosylated by nitric oxide donors. 24418849 7 16 theme physiological 1326:1338 arg1 functions 1340:1348 distinct or overlapping cellular and physiological functions 1289:1348 distinct or overlapping cellular and physiological functions 1289:1348 Taken together, our findings uncover novel and diverse pannexin post-translational modifications suggesting that they may be differentially regulated for distinct or overlapping cellular and physiological functions. 24418849 0 17 theme post-translational 8:25 arg1 modifications 27:39 Diverse post-translational modifications 0:39 Diverse post-translational modifications of the pannexin family of channel-forming proteins 0:90 Diverse post-translational modifications of the pannexin family of channel-forming proteins. 24418849 6 18 theme oxide 1121:1125 arg1 donors 1127:1132 nitric oxide donors 1114:1132 nitric oxide donors 1114:1132 Panx3, on the other hand, is not subject to caspase digestion but an in vitro biotin switch assay revealed that it was S-nitrosylated by nitric oxide donors. 24418849 7 19 theme diverse 1182:1188 arg1 modifications 1218:1230 novel and diverse pannexin post-translational modifications 1172:1230 novel and diverse pannexin post-translational modifications suggesting that they may be differentially regulated for distinct or overlapping cellular and physiological functions 1172:1348 Taken together, our findings uncover novel and diverse pannexin post-translational modifications suggesting that they may be differentially regulated for distinct or overlapping cellular and physiological functions. 24418849 1 20 theme pannexin 97:104 arg1 family 106:111 The pannexin family 93:111 The pannexin family of channel-forming proteins 93:139 The pannexin family of channel-forming proteins is composed of 3 distinct but related members called Panx1, Panx2, and Panx3. 24418849 7 21 theme overlapping 1301:1311 arg1 functions 1340:1348 distinct or overlapping cellular and physiological functions 1289:1348 distinct or overlapping cellular and physiological functions 1289:1348 Taken together, our findings uncover novel and diverse pannexin post-translational modifications suggesting that they may be differentially regulated for distinct or overlapping cellular and physiological functions. 24418849 0 22 theme Diverse 0:6 arg1 modifications 27:39 Diverse post-translational modifications 0:39 Diverse post-translational modifications of the pannexin family of channel-forming proteins 0:90 Diverse post-translational modifications of the pannexin family of channel-forming proteins. 24418849 4 23 theme biochemical 559:569 arg1 assays 571:576 in vitro biochemical assays 550:576 in vitro biochemical assays performed on ectopically expressed pannexins in HEK-293T cells 550:639 Using in vitro biochemical assays performed on ectopically expressed pannexins in HEK-293T cells, we confirmed that all 3 pannexins are N-glycosylated to different degrees, but they are not modified by sialylation or O-linked glycosylation in a manner that changes their apparent molecular weight. 24418849 6 24 theme nitric 1114:1119 arg1 donors 1127:1132 nitric oxide donors 1114:1132 nitric oxide donors 1114:1132 Panx3, on the other hand, is not subject to caspase digestion but an in vitro biotin switch assay revealed that it was S-nitrosylated by nitric oxide donors. 24418849 7 25 theme cellular 1313:1320 arg1 functions 1340:1348 distinct or overlapping cellular and physiological functions 1289:1348 distinct or overlapping cellular and physiological functions 1289:1348 Taken together, our findings uncover novel and diverse pannexin post-translational modifications suggesting that they may be differentially regulated for distinct or overlapping cellular and physiological functions. 24418849 6 26 dep in 1046:1047 arg1 vitro 1049:1053 vitro 1049:1053 vitro 1049:1053 Panx3, on the other hand, is not subject to caspase digestion but an in vitro biotin switch assay revealed that it was S-nitrosylated by nitric oxide donors. 24418849 3 27 theme different 452:460 arg1 modifications 481:493 similar or different post-translational modifications 441:493 similar or different post-translational modifications 441:493 However, it is currently unclear if all pannexins are subject to similar or different post-translational modifications as most studies have focused primarily on Panx1. 24418849 1 28 theme channel-forming 116:130 arg1 proteins 132:139 channel-forming proteins 116:139 channel-forming proteins 116:139 The pannexin family of channel-forming proteins is composed of 3 distinct but related members called Panx1, Panx2, and Panx3. 24418849 3 29 theme post-translational 462:479 arg1 modifications 481:493 similar or different post-translational modifications 441:493 similar or different post-translational modifications 441:493 However, it is currently unclear if all pannexins are subject to similar or different post-translational modifications as most studies have focused primarily on Panx1. 24418849 0 30 theme pannexin 48:55 arg1 family 57:62 the pannexin family 44:62 the pannexin family of channel-forming proteins 44:90 Diverse post-translational modifications of the pannexin family of channel-forming proteins. 24418849 5 31 theme caspase 858:864 arg1 assays 866:871 cell-free caspase assays 848:871 cell-free caspase assays 848:871 Using cell-free caspase assays, we also discovered that similar to Panx1, the C-terminus of Panx2 is a substrate for caspase cleavage. 24418849 4 32 theme molecular 824:832 arg1 weight 834:839 their apparent molecular weight 809:839 their apparent molecular weight 809:839 Using in vitro biochemical assays performed on ectopically expressed pannexins in HEK-293T cells, we confirmed that all 3 pannexins are N-glycosylated to different degrees, but they are not modified by sialylation or O-linked glycosylation in a manner that changes their apparent molecular weight. 24418849 3 33 theme similar 441:447 arg1 modifications 481:493 similar or different post-translational modifications 441:493 similar or different post-translational modifications 441:493 However, it is currently unclear if all pannexins are subject to similar or different post-translational modifications as most studies have focused primarily on Panx1. 24418849 4 34 theme apparent 815:822 arg1 weight 834:839 their apparent molecular weight 809:839 their apparent molecular weight 809:839 Using in vitro biochemical assays performed on ectopically expressed pannexins in HEK-293T cells, we confirmed that all 3 pannexins are N-glycosylated to different degrees, but they are not modified by sialylation or O-linked glycosylation in a manner that changes their apparent molecular weight. 24418849 7 35 theme pannexin 1190:1197 arg1 modifications 1218:1230 novel and diverse pannexin post-translational modifications 1172:1230 novel and diverse pannexin post-translational modifications suggesting that they may be differentially regulated for distinct or overlapping cellular and physiological functions 1172:1348 Taken together, our findings uncover novel and diverse pannexin post-translational modifications suggesting that they may be differentially regulated for distinct or overlapping cellular and physiological functions. 24418849 5 36 theme caspase 959:965 arg1 cleavage 967:974 caspase cleavage 959:974 caspase cleavage 959:974 Using cell-free caspase assays, we also discovered that similar to Panx1, the C-terminus of Panx2 is a substrate for caspase cleavage. 24418849 3 37 theme most 498:501 arg1 studies 503:509 most studies 498:509 most studies 498:509 However, it is currently unclear if all pannexins are subject to similar or different post-translational modifications as most studies have focused primarily on Panx1. 24418849 0 38 theme family 57:62 arg1 modifications 27:39 Diverse post-translational modifications 0:39 Diverse post-translational modifications of the pannexin family of channel-forming proteins 0:90 Diverse post-translational modifications of the pannexin family of channel-forming proteins. 24418849 4 39 theme in 550:551 arg1 assays 571:576 in vitro biochemical assays 550:576 in vitro biochemical assays performed on ectopically expressed pannexins in HEK-293T cells 550:639 Using in vitro biochemical assays performed on ectopically expressed pannexins in HEK-293T cells, we confirmed that all 3 pannexins are N-glycosylated to different degrees, but they are not modified by sialylation or O-linked glycosylation in a manner that changes their apparent molecular weight. 24418849 2 40 theme physiological 258:270 arg1 processes 272:280 many physiological processes 253:280 many physiological processes as well as pathological conditions 253:315 Pannexins have been implicated in many physiological processes as well as pathological conditions, primarily through their function as ATP release channels. 24418849 4 41 theme HEK-293T 626:633 arg1 cells 635:639 HEK-293T cells 626:639 HEK-293T cells 626:639 Using in vitro biochemical assays performed on ectopically expressed pannexins in HEK-293T cells, we confirmed that all 3 pannexins are N-glycosylated to different degrees, but they are not modified by sialylation or O-linked glycosylation in a manner that changes their apparent molecular weight. 24418849 2 42 theme many 253:256 arg1 processes 272:280 many physiological processes 253:280 many physiological processes as well as pathological conditions 253:315 Pannexins have been implicated in many physiological processes as well as pathological conditions, primarily through their function as ATP release channels. 24418849 4 43 link O-linked 761:768 arg1 glycosylation 770:782 O-linked glycosylation 761:782 O-linked glycosylation 761:782 Using in vitro biochemical assays performed on ectopically expressed pannexins in HEK-293T cells, we confirmed that all 3 pannexins are N-glycosylated to different degrees, but they are not modified by sialylation or O-linked glycosylation in a manner that changes their apparent molecular weight. 24418849 0 44 theme proteins 83:90 arg1 family 57:62 the pannexin family 44:62 the pannexin family of channel-forming proteins 44:90 Diverse post-translational modifications of the pannexin family of channel-forming proteins. 24418849 6 45 theme switch 1062:1067 arg1 assay 1069:1073 an in vitro biotin switch assay 1043:1073 an in vitro biotin switch assay 1043:1073 Panx3, on the other hand, is not subject to caspase digestion but an in vitro biotin switch assay revealed that it was S-nitrosylated by nitric oxide donors. 24418849 6 46 theme caspase 1021:1027 arg1 digestion 1029:1037 caspase digestion 1021:1037 caspase digestion 1021:1037 Panx3, on the other hand, is not subject to caspase digestion but an in vitro biotin switch assay revealed that it was S-nitrosylated by nitric oxide donors. 24418849 4 47 theme different 698:706 arg1 degrees 708:714 different degrees 698:714 different degrees 698:714 Using in vitro biochemical assays performed on ectopically expressed pannexins in HEK-293T cells, we confirmed that all 3 pannexins are N-glycosylated to different degrees, but they are not modified by sialylation or O-linked glycosylation in a manner that changes their apparent molecular weight. 24418849 7 48 theme distinct 1289:1296 arg1 functions 1340:1348 distinct or overlapping cellular and physiological functions 1289:1348 distinct or overlapping cellular and physiological functions 1289:1348 Taken together, our findings uncover novel and diverse pannexin post-translational modifications suggesting that they may be differentially regulated for distinct or overlapping cellular and physiological functions. 24418849 0 49 theme channel-forming 67:81 arg1 proteins 83:90 channel-forming proteins 67:90 channel-forming proteins 67:90 Diverse post-translational modifications of the pannexin family of channel-forming proteins. 24418849 4 50 dep in 550:551 arg1 vitro 553:557 vitro 553:557 vitro 553:557 Using in vitro biochemical assays performed on ectopically expressed pannexins in HEK-293T cells, we confirmed that all 3 pannexins are N-glycosylated to different degrees, but they are not modified by sialylation or O-linked glycosylation in a manner that changes their apparent molecular weight. 24418849 1 51 theme distinct 158:165 arg1 members 179:185 3 distinct but related members 156:185 3 distinct but related members called Panx1, Panx2, and Panx3 156:216 The pannexin family of channel-forming proteins is composed of 3 distinct but related members called Panx1, Panx2, and Panx3. 24418849 7 52 theme post-translational 1199:1216 arg1 modifications 1218:1230 novel and diverse pannexin post-translational modifications 1172:1230 novel and diverse pannexin post-translational modifications suggesting that they may be differentially regulated for distinct or overlapping cellular and physiological functions 1172:1348 Taken together, our findings uncover novel and diverse pannexin post-translational modifications suggesting that they may be differentially regulated for distinct or overlapping cellular and physiological functions. 24418849 6 53 theme other 991:995 arg1 hand 997:1000 the other hand 987:1000 the other hand 987:1000 Panx3, on the other hand, is not subject to caspase digestion but an in vitro biotin switch assay revealed that it was S-nitrosylated by nitric oxide donors. 29201936 3 0 theme B-derived 350:358 arg1 molecules 370:378 granzyme B-derived chaperone molecules 341:378 granzyme B-derived chaperone molecules fused to a fluorescent protein payload and expressed these constructs in natural killer (NK) cells 341:477 We designed and constructed granzyme B-derived chaperone molecules fused to a fluorescent protein payload and expressed these constructs in natural killer (NK) cells. 29201936 6 1 theme necessary 1094:1102 arg1 functional 1224:1233 functional 1224:1233 functional 1224:1233 Combining our functional data with an analysis of the crystal structure of granzyme B suggests that the necessary motifs for granzyme B loading into lytic granules are dispersed throughout the primary amino acid sequence and are only functional when contiguous in the tertiary structure. 29201936 6 1 theme necessary 1094:1102 arg1 motifs 1104:1109 the necessary motifs 1090:1109 the necessary motifs for granzyme B loading into lytic granules 1090:1152 Combining our functional data with an analysis of the crystal structure of granzyme B suggests that the necessary motifs for granzyme B loading into lytic granules are dispersed throughout the primary amino acid sequence and are only functional when contiguous in the tertiary structure. 29201936 7 2 theme cell-based 1448:1457 arg1 therapies 1459:1467 cell-based therapies 1448:1467 cell-based therapies 1448:1467 These results illustrate that by using granzyme B as a molecular chaperone the granzyme-perforin pathway can be exploited as a programmable molecular delivery system for cell-based therapies. 29201936 6 3 theme structure 1052:1060 arg1 analysis 1028:1035 an analysis 1025:1035 an analysis of the crystal structure of granzyme B 1025:1074 Combining our functional data with an analysis of the crystal structure of granzyme B suggests that the necessary motifs for granzyme B loading into lytic granules are dispersed throughout the primary amino acid sequence and are only functional when contiguous in the tertiary structure. 29201936 3 4 theme chaperone 360:368 arg1 molecules 370:378 granzyme B-derived chaperone molecules 341:378 granzyme B-derived chaperone molecules fused to a fluorescent protein payload and expressed these constructs in natural killer (NK) cells 341:477 We designed and constructed granzyme B-derived chaperone molecules fused to a fluorescent protein payload and expressed these constructs in natural killer (NK) cells. 29201936 5 5 theme N-linked 826:833 arg1 sites 849:853 putative N-linked glycosylation sites 817:853 putative N-linked glycosylation sites in granzyme B 817:867 A synthetic chaperone consisting of the granzyme B ER signal peptide and a domain encompassing putative N-linked glycosylation sites in granzyme B is insufficient for payload transfer to target cells, whereas full-length granzyme B is sufficient for payload delivery. 29201936 5 6 dep insufficient 872:883 arg1 chaperone 734:742 A synthetic chaperone 722:742 A synthetic chaperone consisting of the granzyme B ER signal peptide and a domain encompassing putative N-linked glycosylation sites in granzyme B 722:867 A synthetic chaperone consisting of the granzyme B ER signal peptide and a domain encompassing putative N-linked glycosylation sites in granzyme B is insufficient for payload transfer to target cells, whereas full-length granzyme B is sufficient for payload delivery. 29201936 5 6 dep insufficient 872:883 arg1 insufficient 872:883 insufficient 872:883 insufficient 872:883 A synthetic chaperone consisting of the granzyme B ER signal peptide and a domain encompassing putative N-linked glycosylation sites in granzyme B is insufficient for payload transfer to target cells, whereas full-length granzyme B is sufficient for payload delivery. 29201936 5 6 dep insufficient 872:883 arg1 whereas 923:929 whereas 923:929 whereas 923:929 A synthetic chaperone consisting of the granzyme B ER signal peptide and a domain encompassing putative N-linked glycosylation sites in granzyme B is insufficient for payload transfer to target cells, whereas full-length granzyme B is sufficient for payload delivery. 29201936 6 7 theme lytic 1139:1143 arg1 granules 1145:1152 lytic granules 1139:1152 lytic granules 1139:1152 Combining our functional data with an analysis of the crystal structure of granzyme B suggests that the necessary motifs for granzyme B loading into lytic granules are dispersed throughout the primary amino acid sequence and are only functional when contiguous in the tertiary structure. 29201936 6 8 from structure 1267:1275 arg1 contiguous 1240:1249 contiguous 1240:1249 contiguous 1240:1249 Combining our functional data with an analysis of the crystal structure of granzyme B suggests that the necessary motifs for granzyme B loading into lytic granules are dispersed throughout the primary amino acid sequence and are only functional when contiguous in the tertiary structure. 29201936 4 9 theme chaperone-mediated 608:625 arg1 transfer 627:634 the chaperone-mediated transfer 604:634 the chaperone-mediated transfer of the fluorescent protein payload from NK to target cells in co-culture experiments 604:719 Using confocal microscopy and flow cytometry, we investigated the co-localization of the chaperones with lytic granules and the chaperone-mediated transfer of the fluorescent protein payload from NK to target cells in co-culture experiments. 29201936 3 10 theme fluorescent 391:401 arg1 protein 403:409 a fluorescent protein 389:409 a fluorescent protein payload and expressed these constructs in natural killer (NK) cells 389:477 We designed and constructed granzyme B-derived chaperone molecules fused to a fluorescent protein payload and expressed these constructs in natural killer (NK) cells. 29201936 6 11 theme tertiary 1258:1265 arg1 structure 1267:1275 the tertiary structure 1254:1275 the tertiary structure 1254:1275 Combining our functional data with an analysis of the crystal structure of granzyme B suggests that the necessary motifs for granzyme B loading into lytic granules are dispersed throughout the primary amino acid sequence and are only functional when contiguous in the tertiary structure. 29201936 5 12 theme signal 776:781 arg1 peptide 783:789 the granzyme B ER signal peptide 758:789 the granzyme B ER signal peptide 758:789 A synthetic chaperone consisting of the granzyme B ER signal peptide and a domain encompassing putative N-linked glycosylation sites in granzyme B is insufficient for payload transfer to target cells, whereas full-length granzyme B is sufficient for payload delivery. 29201936 4 13 theme flow 510:513 arg1 cytometry 515:523 flow cytometry 510:523 flow cytometry 510:523 Using confocal microscopy and flow cytometry, we investigated the co-localization of the chaperones with lytic granules and the chaperone-mediated transfer of the fluorescent protein payload from NK to target cells in co-culture experiments. 29201936 5 14 theme target 909:914 arg1 cells 916:920 target cells 909:920 target cells 909:920 A synthetic chaperone consisting of the granzyme B ER signal peptide and a domain encompassing putative N-linked glycosylation sites in granzyme B is insufficient for payload transfer to target cells, whereas full-length granzyme B is sufficient for payload delivery. 29201936 6 15 theme amino 1191:1195 arg1 sequence 1202:1209 the primary amino acid sequence 1179:1209 the primary amino acid sequence 1179:1209 Combining our functional data with an analysis of the crystal structure of granzyme B suggests that the necessary motifs for granzyme B loading into lytic granules are dispersed throughout the primary amino acid sequence and are only functional when contiguous in the tertiary structure. 29201936 5 16 theme payload 889:895 arg1 transfer 897:904 payload transfer 889:904 payload transfer to target cells 889:920 A synthetic chaperone consisting of the granzyme B ER signal peptide and a domain encompassing putative N-linked glycosylation sites in granzyme B is insufficient for payload transfer to target cells, whereas full-length granzyme B is sufficient for payload delivery. 29201936 4 17 theme co-culture 698:707 arg1 experiments 709:719 co-culture experiments 698:719 co-culture experiments 698:719 Using confocal microscopy and flow cytometry, we investigated the co-localization of the chaperones with lytic granules and the chaperone-mediated transfer of the fluorescent protein payload from NK to target cells in co-culture experiments. 29201936 5 18 theme granzyme 858:865 arg1 B 867:867 granzyme B 858:867 granzyme B 858:867 A synthetic chaperone consisting of the granzyme B ER signal peptide and a domain encompassing putative N-linked glycosylation sites in granzyme B is insufficient for payload transfer to target cells, whereas full-length granzyme B is sufficient for payload delivery. 29201936 3 19 theme natural 453:459 arg1 NK 469:470 NK 469:470 NK 469:470 We designed and constructed granzyme B-derived chaperone molecules fused to a fluorescent protein payload and expressed these constructs in natural killer (NK) cells. 29201936 3 19 theme natural 453:459 arg1 killer 461:466 natural killer 453:466 natural killer (NK) cells 453:477 We designed and constructed granzyme B-derived chaperone molecules fused to a fluorescent protein payload and expressed these constructs in natural killer (NK) cells. 29201936 2 20 theme delivery 296:303 arg1 module 305:310 a cell-to-cell protein delivery module 273:310 a cell-to-cell protein delivery module 273:310 Here, we report utilization of the granzyme-perforin pathway of cytotoxic lymphocytes as a cell-to-cell protein delivery module. 29201936 6 21 from contiguous 1240:1249 arg1 structure 1267:1275 the tertiary structure 1254:1275 the tertiary structure 1254:1275 Combining our functional data with an analysis of the crystal structure of granzyme B suggests that the necessary motifs for granzyme B loading into lytic granules are dispersed throughout the primary amino acid sequence and are only functional when contiguous in the tertiary structure. 29201936 0 22 theme Cell-to-Cell 9:20 arg1 Delivery 22:29 Targeted Cell-to-Cell Delivery 0:29 Targeted Cell-to-Cell Delivery of Protein Payloads via the Granzyme-Perforin Pathway. 0:84 Targeted Cell-to-Cell Delivery of Protein Payloads via the Granzyme-Perforin Pathway. 29201936 5 23 theme putative 817:824 arg1 sites 849:853 putative N-linked glycosylation sites 817:853 putative N-linked glycosylation sites in granzyme B 817:867 A synthetic chaperone consisting of the granzyme B ER signal peptide and a domain encompassing putative N-linked glycosylation sites in granzyme B is insufficient for payload transfer to target cells, whereas full-length granzyme B is sufficient for payload delivery. 29201936 7 24 theme granzyme 1317:1324 arg1 chaperone 1343:1351 a molecular chaperone 1331:1351 a molecular chaperone 1331:1351 These results illustrate that by using granzyme B as a molecular chaperone the granzyme-perforin pathway can be exploited as a programmable molecular delivery system for cell-based therapies. 29201936 7 24 theme granzyme 1317:1324 arg1 B 1326:1326 granzyme B 1317:1326 granzyme B 1317:1326 These results illustrate that by using granzyme B as a molecular chaperone the granzyme-perforin pathway can be exploited as a programmable molecular delivery system for cell-based therapies. 29201936 3 25 link B-derived 350:358 arg1 molecules 370:378 granzyme B-derived chaperone molecules 341:378 granzyme B-derived chaperone molecules fused to a fluorescent protein payload and expressed these constructs in natural killer (NK) cells 341:477 We designed and constructed granzyme B-derived chaperone molecules fused to a fluorescent protein payload and expressed these constructs in natural killer (NK) cells. 29201936 5 26 theme synthetic 724:732 arg1 chaperone 734:742 A synthetic chaperone 722:742 A synthetic chaperone consisting of the granzyme B ER signal peptide and a domain encompassing putative N-linked glycosylation sites in granzyme B 722:867 A synthetic chaperone consisting of the granzyme B ER signal peptide and a domain encompassing putative N-linked glycosylation sites in granzyme B is insufficient for payload transfer to target cells, whereas full-length granzyme B is sufficient for payload delivery. 29201936 5 26 theme synthetic 724:732 arg1 insufficient 872:883 insufficient 872:883 insufficient 872:883 A synthetic chaperone consisting of the granzyme B ER signal peptide and a domain encompassing putative N-linked glycosylation sites in granzyme B is insufficient for payload transfer to target cells, whereas full-length granzyme B is sufficient for payload delivery. 29201936 5 26 theme synthetic 724:732 arg1 whereas 923:929 whereas 923:929 whereas 923:929 A synthetic chaperone consisting of the granzyme B ER signal peptide and a domain encompassing putative N-linked glycosylation sites in granzyme B is insufficient for payload transfer to target cells, whereas full-length granzyme B is sufficient for payload delivery. 29201936 6 27 theme granzyme 1115:1122 arg1 B loading 1124:1132 granzyme B loading 1115:1132 granzyme B loading into lytic granules 1115:1152 Combining our functional data with an analysis of the crystal structure of granzyme B suggests that the necessary motifs for granzyme B loading into lytic granules are dispersed throughout the primary amino acid sequence and are only functional when contiguous in the tertiary structure. 29201936 0 28 theme Targeted 0:7 arg1 Delivery 22:29 Targeted Cell-to-Cell Delivery 0:29 Targeted Cell-to-Cell Delivery of Protein Payloads via the Granzyme-Perforin Pathway. 0:84 Targeted Cell-to-Cell Delivery of Protein Payloads via the Granzyme-Perforin Pathway. 29201936 1 29 theme great 95:99 arg1 potential 101:109 great potential 95:109 great potential for engineering cellular therapeutics by repurposing biological systems 95:181 There is great potential for engineering cellular therapeutics by repurposing biological systems. 29201936 7 30 theme delivery 1428:1435 arg1 pathway 1375:1381 the granzyme-perforin pathway 1353:1381 the granzyme-perforin pathway 1353:1381 These results illustrate that by using granzyme B as a molecular chaperone the granzyme-perforin pathway can be exploited as a programmable molecular delivery system for cell-based therapies. 29201936 7 30 theme delivery 1428:1435 arg1 system 1437:1442 a programmable molecular delivery system 1403:1442 a programmable molecular delivery system for cell-based therapies 1403:1467 These results illustrate that by using granzyme B as a molecular chaperone the granzyme-perforin pathway can be exploited as a programmable molecular delivery system for cell-based therapies. 29201936 4 31 theme lytic 585:589 arg1 granules 591:598 lytic granules 585:598 lytic granules 585:598 Using confocal microscopy and flow cytometry, we investigated the co-localization of the chaperones with lytic granules and the chaperone-mediated transfer of the fluorescent protein payload from NK to target cells in co-culture experiments. 29201936 7 32 theme programmable 1405:1416 arg1 pathway 1375:1381 the granzyme-perforin pathway 1353:1381 the granzyme-perforin pathway 1353:1381 These results illustrate that by using granzyme B as a molecular chaperone the granzyme-perforin pathway can be exploited as a programmable molecular delivery system for cell-based therapies. 29201936 7 32 theme programmable 1405:1416 arg1 system 1437:1442 a programmable molecular delivery system 1403:1442 a programmable molecular delivery system for cell-based therapies 1403:1467 These results illustrate that by using granzyme B as a molecular chaperone the granzyme-perforin pathway can be exploited as a programmable molecular delivery system for cell-based therapies. 29201936 4 33 dep cells 689:693 arg1 to 679:680 to 679:680 to 679:680 Using confocal microscopy and flow cytometry, we investigated the co-localization of the chaperones with lytic granules and the chaperone-mediated transfer of the fluorescent protein payload from NK to target cells in co-culture experiments. 29201936 7 34 theme granzyme-perforin 1357:1373 arg1 pathway 1375:1381 the granzyme-perforin pathway 1353:1381 the granzyme-perforin pathway 1353:1381 These results illustrate that by using granzyme B as a molecular chaperone the granzyme-perforin pathway can be exploited as a programmable molecular delivery system for cell-based therapies. 29201936 7 34 theme granzyme-perforin 1357:1373 arg1 system 1437:1442 a programmable molecular delivery system 1403:1442 a programmable molecular delivery system for cell-based therapies 1403:1467 These results illustrate that by using granzyme B as a molecular chaperone the granzyme-perforin pathway can be exploited as a programmable molecular delivery system for cell-based therapies. 29201936 6 35 theme acid 1197:1200 arg1 sequence 1202:1209 the primary amino acid sequence 1179:1209 the primary amino acid sequence 1179:1209 Combining our functional data with an analysis of the crystal structure of granzyme B suggests that the necessary motifs for granzyme B loading into lytic granules are dispersed throughout the primary amino acid sequence and are only functional when contiguous in the tertiary structure. 29201936 4 36 theme NK 676:677 arg1 cells 689:693 NK to target cells 676:693 NK to target cells 676:693 Using confocal microscopy and flow cytometry, we investigated the co-localization of the chaperones with lytic granules and the chaperone-mediated transfer of the fluorescent protein payload from NK to target cells in co-culture experiments. 29201936 0 37 theme Payloads 42:49 arg1 Delivery 22:29 Targeted Cell-to-Cell Delivery 0:29 Targeted Cell-to-Cell Delivery of Protein Payloads via the Granzyme-Perforin Pathway. 0:84 Targeted Cell-to-Cell Delivery of Protein Payloads via the Granzyme-Perforin Pathway. 29201936 6 38 theme primary 1183:1189 arg1 sequence 1202:1209 the primary amino acid sequence 1179:1209 the primary amino acid sequence 1179:1209 Combining our functional data with an analysis of the crystal structure of granzyme B suggests that the necessary motifs for granzyme B loading into lytic granules are dispersed throughout the primary amino acid sequence and are only functional when contiguous in the tertiary structure. 29201936 5 39 theme granzyme 762:769 arg1 peptide 783:789 the granzyme B ER signal peptide 758:789 the granzyme B ER signal peptide 758:789 A synthetic chaperone consisting of the granzyme B ER signal peptide and a domain encompassing putative N-linked glycosylation sites in granzyme B is insufficient for payload transfer to target cells, whereas full-length granzyme B is sufficient for payload delivery. 29201936 2 40 theme lymphocytes 258:268 arg1 pathway 237:243 the granzyme-perforin pathway 215:243 the granzyme-perforin pathway of cytotoxic lymphocytes 215:268 Here, we report utilization of the granzyme-perforin pathway of cytotoxic lymphocytes as a cell-to-cell protein delivery module. 29201936 0 41 theme Protein 34:40 arg1 Payloads 42:49 Protein Payloads 34:49 Protein Payloads 34:49 Targeted Cell-to-Cell Delivery of Protein Payloads via the Granzyme-Perforin Pathway. 29201936 6 42 theme functional 1004:1013 arg1 data 1015:1018 our functional data 1000:1018 our functional data 1000:1018 Combining our functional data with an analysis of the crystal structure of granzyme B suggests that the necessary motifs for granzyme B loading into lytic granules are dispersed throughout the primary amino acid sequence and are only functional when contiguous in the tertiary structure. 29201936 3 43 theme killer 461:466 arg1 cells 473:477 natural killer (NK) cells 453:477 natural killer (NK) cells 453:477 We designed and constructed granzyme B-derived chaperone molecules fused to a fluorescent protein payload and expressed these constructs in natural killer (NK) cells. 29201936 6 44 theme crystal 1044:1050 arg1 structure 1052:1060 the crystal structure 1040:1060 the crystal structure of granzyme B 1040:1074 Combining our functional data with an analysis of the crystal structure of granzyme B suggests that the necessary motifs for granzyme B loading into lytic granules are dispersed throughout the primary amino acid sequence and are only functional when contiguous in the tertiary structure. 29201936 2 45 theme cytotoxic 248:256 arg1 lymphocytes 258:268 cytotoxic lymphocytes 248:268 cytotoxic lymphocytes 248:268 Here, we report utilization of the granzyme-perforin pathway of cytotoxic lymphocytes as a cell-to-cell protein delivery module. 29201936 4 46 theme target 682:687 arg1 cells 689:693 NK to target cells 676:693 NK to target cells 676:693 Using confocal microscopy and flow cytometry, we investigated the co-localization of the chaperones with lytic granules and the chaperone-mediated transfer of the fluorescent protein payload from NK to target cells in co-culture experiments. 29201936 5 47 theme ER 773:774 arg1 peptide 783:789 the granzyme B ER signal peptide 758:789 the granzyme B ER signal peptide 758:789 A synthetic chaperone consisting of the granzyme B ER signal peptide and a domain encompassing putative N-linked glycosylation sites in granzyme B is insufficient for payload transfer to target cells, whereas full-length granzyme B is sufficient for payload delivery. 29201936 7 48 theme molecular 1418:1426 arg1 pathway 1375:1381 the granzyme-perforin pathway 1353:1381 the granzyme-perforin pathway 1353:1381 These results illustrate that by using granzyme B as a molecular chaperone the granzyme-perforin pathway can be exploited as a programmable molecular delivery system for cell-based therapies. 29201936 7 48 theme molecular 1418:1426 arg1 system 1437:1442 a programmable molecular delivery system 1403:1442 a programmable molecular delivery system for cell-based therapies 1403:1467 These results illustrate that by using granzyme B as a molecular chaperone the granzyme-perforin pathway can be exploited as a programmable molecular delivery system for cell-based therapies. 29201936 4 49 theme confocal 486:493 arg1 microscopy 495:504 confocal microscopy 486:504 confocal microscopy 486:504 Using confocal microscopy and flow cytometry, we investigated the co-localization of the chaperones with lytic granules and the chaperone-mediated transfer of the fluorescent protein payload from NK to target cells in co-culture experiments. 29201936 5 50 link N-linked 826:833 arg1 sites 849:853 putative N-linked glycosylation sites 817:853 putative N-linked glycosylation sites in granzyme B 817:867 A synthetic chaperone consisting of the granzyme B ER signal peptide and a domain encompassing putative N-linked glycosylation sites in granzyme B is insufficient for payload transfer to target cells, whereas full-length granzyme B is sufficient for payload delivery. 29201936 4 51 with co-localization 546:560 arg1 granules 591:598 lytic granules 585:598 lytic granules 585:598 Using confocal microscopy and flow cytometry, we investigated the co-localization of the chaperones with lytic granules and the chaperone-mediated transfer of the fluorescent protein payload from NK to target cells in co-culture experiments. 29201936 5 52 theme B 771:771 arg1 peptide 783:789 the granzyme B ER signal peptide 758:789 the granzyme B ER signal peptide 758:789 A synthetic chaperone consisting of the granzyme B ER signal peptide and a domain encompassing putative N-linked glycosylation sites in granzyme B is insufficient for payload transfer to target cells, whereas full-length granzyme B is sufficient for payload delivery. 29201936 3 53 theme granzyme 341:348 arg1 molecules 370:378 granzyme B-derived chaperone molecules 341:378 granzyme B-derived chaperone molecules fused to a fluorescent protein payload and expressed these constructs in natural killer (NK) cells 341:477 We designed and constructed granzyme B-derived chaperone molecules fused to a fluorescent protein payload and expressed these constructs in natural killer (NK) cells. 29201936 2 54 theme granzyme-perforin 219:235 arg1 pathway 237:243 the granzyme-perforin pathway 215:243 the granzyme-perforin pathway of cytotoxic lymphocytes 215:268 Here, we report utilization of the granzyme-perforin pathway of cytotoxic lymphocytes as a cell-to-cell protein delivery module. 29201936 2 55 theme pathway 237:243 arg1 utilization 200:210 utilization 200:210 utilization of the granzyme-perforin pathway of cytotoxic lymphocytes as a cell-to-cell protein delivery module 200:310 Here, we report utilization of the granzyme-perforin pathway of cytotoxic lymphocytes as a cell-to-cell protein delivery module. 29201936 1 56 theme cellular 127:134 arg1 therapeutics 136:147 cellular therapeutics 127:147 cellular therapeutics 127:147 There is great potential for engineering cellular therapeutics by repurposing biological systems. 29201936 4 57 theme chaperones 569:578 arg1 transfer 627:634 the chaperone-mediated transfer 604:634 the chaperone-mediated transfer of the fluorescent protein payload from NK to target cells in co-culture experiments 604:719 Using confocal microscopy and flow cytometry, we investigated the co-localization of the chaperones with lytic granules and the chaperone-mediated transfer of the fluorescent protein payload from NK to target cells in co-culture experiments. 29201936 4 57 theme chaperones 569:578 arg1 co-localization 546:560 the co-localization 542:560 the co-localization of the chaperones with lytic granules 542:598 Using confocal microscopy and flow cytometry, we investigated the co-localization of the chaperones with lytic granules and the chaperone-mediated transfer of the fluorescent protein payload from NK to target cells in co-culture experiments. 29201936 5 58 gly glycosylation 835:847 arg2 sites 849:853 putative N-linked glycosylation sites 817:853 putative N-linked glycosylation sites in granzyme B 817:867 A synthetic chaperone consisting of the granzyme B ER signal peptide and a domain encompassing putative N-linked glycosylation sites in granzyme B is insufficient for payload transfer to target cells, whereas full-length granzyme B is sufficient for payload delivery. 29201936 2 59 theme protein 288:294 arg1 module 305:310 a cell-to-cell protein delivery module 273:310 a cell-to-cell protein delivery module 273:310 Here, we report utilization of the granzyme-perforin pathway of cytotoxic lymphocytes as a cell-to-cell protein delivery module. 29201936 6 60 theme B 1074:1074 arg1 structure 1052:1060 the crystal structure 1040:1060 the crystal structure of granzyme B 1040:1074 Combining our functional data with an analysis of the crystal structure of granzyme B suggests that the necessary motifs for granzyme B loading into lytic granules are dispersed throughout the primary amino acid sequence and are only functional when contiguous in the tertiary structure. 29201936 5 61 theme payload 972:978 arg1 delivery 980:987 payload delivery 972:987 payload delivery 972:987 A synthetic chaperone consisting of the granzyme B ER signal peptide and a domain encompassing putative N-linked glycosylation sites in granzyme B is insufficient for payload transfer to target cells, whereas full-length granzyme B is sufficient for payload delivery. 29201936 4 62 theme protein 655:661 arg1 transfer 627:634 the chaperone-mediated transfer 604:634 the chaperone-mediated transfer of the fluorescent protein payload from NK to target cells in co-culture experiments 604:719 Using confocal microscopy and flow cytometry, we investigated the co-localization of the chaperones with lytic granules and the chaperone-mediated transfer of the fluorescent protein payload from NK to target cells in co-culture experiments. 29201936 4 62 theme protein 655:661 arg1 co-localization 546:560 the co-localization 542:560 the co-localization of the chaperones with lytic granules 542:598 Using confocal microscopy and flow cytometry, we investigated the co-localization of the chaperones with lytic granules and the chaperone-mediated transfer of the fluorescent protein payload from NK to target cells in co-culture experiments. 29201936 3 63 dep protein 403:409 arg1 expressed 423:431 expressed 423:431 expressed these constructs in natural killer (NK) cells 423:477 We designed and constructed granzyme B-derived chaperone molecules fused to a fluorescent protein payload and expressed these constructs in natural killer (NK) cells. 29201936 3 63 dep protein 403:409 arg1 payload 411:417 payload 411:417 payload 411:417 We designed and constructed granzyme B-derived chaperone molecules fused to a fluorescent protein payload and expressed these constructs in natural killer (NK) cells. 29201936 7 64 theme molecular 1333:1341 arg1 chaperone 1343:1351 a molecular chaperone 1331:1351 a molecular chaperone 1331:1351 These results illustrate that by using granzyme B as a molecular chaperone the granzyme-perforin pathway can be exploited as a programmable molecular delivery system for cell-based therapies. 29201936 7 64 theme molecular 1333:1341 arg1 B 1326:1326 granzyme B 1317:1326 granzyme B 1317:1326 These results illustrate that by using granzyme B as a molecular chaperone the granzyme-perforin pathway can be exploited as a programmable molecular delivery system for cell-based therapies. 29201936 2 65 theme cell-to-cell 275:286 arg1 module 305:310 a cell-to-cell protein delivery module 273:310 a cell-to-cell protein delivery module 273:310 Here, we report utilization of the granzyme-perforin pathway of cytotoxic lymphocytes as a cell-to-cell protein delivery module. 29201936 5 66 theme granzyme 943:950 arg1 B 952:952 full-length granzyme B 931:952 full-length granzyme B 931:952 A synthetic chaperone consisting of the granzyme B ER signal peptide and a domain encompassing putative N-linked glycosylation sites in granzyme B is insufficient for payload transfer to target cells, whereas full-length granzyme B is sufficient for payload delivery. 29201936 4 67 theme fluorescent 643:653 arg1 protein 655:661 the fluorescent protein 639:661 the fluorescent protein payload from NK to target cells in co-culture experiments 639:719 Using confocal microscopy and flow cytometry, we investigated the co-localization of the chaperones with lytic granules and the chaperone-mediated transfer of the fluorescent protein payload from NK to target cells in co-culture experiments. 29201936 4 68 with transfer 627:634 arg1 granules 591:598 lytic granules 585:598 lytic granules 585:598 Using confocal microscopy and flow cytometry, we investigated the co-localization of the chaperones with lytic granules and the chaperone-mediated transfer of the fluorescent protein payload from NK to target cells in co-culture experiments. 29201936 5 69 theme full-length 931:941 arg1 B 952:952 full-length granzyme B 931:952 full-length granzyme B 931:952 A synthetic chaperone consisting of the granzyme B ER signal peptide and a domain encompassing putative N-linked glycosylation sites in granzyme B is insufficient for payload transfer to target cells, whereas full-length granzyme B is sufficient for payload delivery. 29201936 6 70 theme granzyme 1065:1072 arg1 B 1074:1074 granzyme B 1065:1074 granzyme B 1065:1074 Combining our functional data with an analysis of the crystal structure of granzyme B suggests that the necessary motifs for granzyme B loading into lytic granules are dispersed throughout the primary amino acid sequence and are only functional when contiguous in the tertiary structure. 29201936 0 71 theme Granzyme-Perforin 59:75 arg1 Pathway 77:83 the Granzyme-Perforin Pathway 55:83 the Granzyme-Perforin Pathway 55:83 Targeted Cell-to-Cell Delivery of Protein Payloads via the Granzyme-Perforin Pathway. 29201936 5 72 from sites 849:853 arg1 B 867:867 granzyme B 858:867 granzyme B 858:867 A synthetic chaperone consisting of the granzyme B ER signal peptide and a domain encompassing putative N-linked glycosylation sites in granzyme B is insufficient for payload transfer to target cells, whereas full-length granzyme B is sufficient for payload delivery. 29201936 5 73 theme glycosylation 835:847 arg1 sites 849:853 putative N-linked glycosylation sites 817:853 putative N-linked glycosylation sites in granzyme B 817:867 A synthetic chaperone consisting of the granzyme B ER signal peptide and a domain encompassing putative N-linked glycosylation sites in granzyme B is insufficient for payload transfer to target cells, whereas full-length granzyme B is sufficient for payload delivery. 29201936 1 74 theme biological 164:173 arg1 systems 175:181 biological systems 164:181 biological systems 164:181 There is great potential for engineering cellular therapeutics by repurposing biological systems. 28842020 0 0 theme selective 101:109 arg1 enrichment 111:120 highly selective enrichment 94:120 highly selective enrichment of N-linked glycopeptides 94:146 One-step synthesis of carboxyl-functionalized metal-organic framework with binary ligands for highly selective enrichment of N-linked glycopeptides. 28842020 4 1 theme samples 791:797 arg1 digests 732:738 tryptic digests 724:738 tryptic digests of standard glycoproteins and practical biological samples 724:797 The as-prepared material demonstrated excellent performance for selective enrichment of glycopeptides from tryptic digests of standard glycoproteins and practical biological samples. 28842020 1 2 theme glycopeptides 194:206 arg1 enrichment 180:189 Highly efficient and selective enrichment 149:189 Highly efficient and selective enrichment of glycopeptides from complex biosamples 149:230 Highly efficient and selective enrichment of glycopeptides from complex biosamples is vital prior to mass spectrometry analysis. 28842020 4 3 theme as-prepared 621:631 arg1 material 633:640 The as-prepared material 617:640 The as-prepared material 617:640 The as-prepared material demonstrated excellent performance for selective enrichment of glycopeptides from tryptic digests of standard glycoproteins and practical biological samples. 28842020 3 4 theme selective 578:586 arg1 enrichment 588:597 selective enrichment 578:597 selective enrichment of glycopeptides 578:614 Compared with pure UiO-66 with one ligand, UiO-66-COOH containing binary ligands demonstrated greater hydrophilicity and performed much better in selective enrichment of glycopeptides. 28842020 3 5 theme glycopeptides 602:614 arg1 enrichment 588:597 selective enrichment 578:597 selective enrichment of glycopeptides 578:614 Compared with pure UiO-66 with one ligand, UiO-66-COOH containing binary ligands demonstrated greater hydrophilicity and performed much better in selective enrichment of glycopeptides. 28842020 4 6 theme excellent 655:663 arg1 performance 665:675 excellent performance 655:675 excellent performance for selective enrichment of glycopeptides from tryptic digests of standard glycoproteins and practical biological samples 655:797 The as-prepared material demonstrated excellent performance for selective enrichment of glycopeptides from tryptic digests of standard glycoproteins and practical biological samples. 28842020 4 7 gly glycoproteins 752:764 arg1 glycoproteins 752:764 standard glycoproteins 743:764 standard glycoproteins 743:764 The as-prepared material demonstrated excellent performance for selective enrichment of glycopeptides from tryptic digests of standard glycoproteins and practical biological samples. 28842020 2 8 theme organic 312:318 arg1 framework 320:328 a hydrophilic metal organic framework 292:328 a hydrophilic metal organic framework with free carboxylic groups (denoted as UiO-66-COOH) 292:381 In this work, a hydrophilic metal organic framework with free carboxylic groups (denoted as UiO-66-COOH) was synthesized in one step with binary ligands. 28842020 4 9 from digests 732:738 arg1 enrichment 691:700 selective enrichment 681:700 selective enrichment of glycopeptides from tryptic digests of standard glycoproteins and practical biological samples 681:797 The as-prepared material demonstrated excellent performance for selective enrichment of glycopeptides from tryptic digests of standard glycoproteins and practical biological samples. 28842020 0 10 theme glycopeptides 134:146 arg1 enrichment 111:120 highly selective enrichment 94:120 highly selective enrichment of N-linked glycopeptides 94:146 One-step synthesis of carboxyl-functionalized metal-organic framework with binary ligands for highly selective enrichment of N-linked glycopeptides. 28842020 2 11 theme metal 306:310 arg1 framework 320:328 a hydrophilic metal organic framework 292:328 a hydrophilic metal organic framework with free carboxylic groups (denoted as UiO-66-COOH) 292:381 In this work, a hydrophilic metal organic framework with free carboxylic groups (denoted as UiO-66-COOH) was synthesized in one step with binary ligands. 28842020 4 12 theme glycoproteins 752:764 arg1 digests 732:738 tryptic digests 724:738 tryptic digests of standard glycoproteins and practical biological samples 724:797 The as-prepared material demonstrated excellent performance for selective enrichment of glycopeptides from tryptic digests of standard glycoproteins and practical biological samples. 28842020 2 13 theme binary 416:421 arg1 ligands 423:429 binary ligands 416:429 binary ligands 416:429 In this work, a hydrophilic metal organic framework with free carboxylic groups (denoted as UiO-66-COOH) was synthesized in one step with binary ligands. 28842020 0 14 theme N-linked 125:132 arg1 glycopeptides 134:146 N-linked glycopeptides 125:146 N-linked glycopeptides 125:146 One-step synthesis of carboxyl-functionalized metal-organic framework with binary ligands for highly selective enrichment of N-linked glycopeptides. 28842020 4 15 gly glycopeptides 705:717 arg2 glycopeptides 705:717 glycopeptides 705:717 glycopeptides 705:717 The as-prepared material demonstrated excellent performance for selective enrichment of glycopeptides from tryptic digests of standard glycoproteins and practical biological samples. 28842020 2 16 theme hydrophilic 294:304 arg1 framework 320:328 a hydrophilic metal organic framework 292:328 a hydrophilic metal organic framework with free carboxylic groups (denoted as UiO-66-COOH) 292:381 In this work, a hydrophilic metal organic framework with free carboxylic groups (denoted as UiO-66-COOH) was synthesized in one step with binary ligands. 28842020 1 17 theme complex 213:219 arg1 biosamples 221:230 complex biosamples 213:230 complex biosamples 213:230 Highly efficient and selective enrichment of glycopeptides from complex biosamples is vital prior to mass spectrometry analysis. 28842020 3 18 with UiO-66 451:456 arg1 ligand 467:472 one ligand 463:472 one ligand 463:472 Compared with pure UiO-66 with one ligand, UiO-66-COOH containing binary ligands demonstrated greater hydrophilicity and performed much better in selective enrichment of glycopeptides. 28842020 3 19 theme pure 446:449 arg1 UiO-66 451:456 pure UiO-66 446:456 pure UiO-66 with one ligand 446:472 Compared with pure UiO-66 with one ligand, UiO-66-COOH containing binary ligands demonstrated greater hydrophilicity and performed much better in selective enrichment of glycopeptides. 28842020 0 20 theme One-step 0:7 arg1 synthesis 9:17 One-step synthesis 0:17 One-step synthesis of carboxyl-functionalized metal-organic framework with binary ligands for highly selective enrichment of N-linked glycopeptides. 0:147 One-step synthesis of carboxyl-functionalized metal-organic framework with binary ligands for highly selective enrichment of N-linked glycopeptides. 28842020 2 21 theme carboxylic 340:349 arg1 groups 351:356 free carboxylic groups 335:356 free carboxylic groups (denoted as UiO-66-COOH) 335:381 In this work, a hydrophilic metal organic framework with free carboxylic groups (denoted as UiO-66-COOH) was synthesized in one step with binary ligands. 28842020 4 22 theme standard 743:750 arg1 glycoproteins 752:764 standard glycoproteins 743:764 standard glycoproteins 743:764 The as-prepared material demonstrated excellent performance for selective enrichment of glycopeptides from tryptic digests of standard glycoproteins and practical biological samples. 28842020 0 23 theme carboxyl-functionalized 22:44 arg1 framework 60:68 carboxyl-functionalized metal-organic framework 22:68 carboxyl-functionalized metal-organic framework 22:68 One-step synthesis of carboxyl-functionalized metal-organic framework with binary ligands for highly selective enrichment of N-linked glycopeptides. 28842020 2 24 theme free 335:338 arg1 groups 351:356 free carboxylic groups 335:356 free carboxylic groups (denoted as UiO-66-COOH) 335:381 In this work, a hydrophilic metal organic framework with free carboxylic groups (denoted as UiO-66-COOH) was synthesized in one step with binary ligands. 28842020 4 25 theme glycopeptides 705:717 arg1 enrichment 691:700 selective enrichment 681:700 selective enrichment of glycopeptides from tryptic digests of standard glycoproteins and practical biological samples 681:797 The as-prepared material demonstrated excellent performance for selective enrichment of glycopeptides from tryptic digests of standard glycoproteins and practical biological samples. 28842020 0 26 gly glycopeptides 134:146 arg2 glycopeptides 134:146 N-linked glycopeptides 125:146 N-linked glycopeptides 125:146 One-step synthesis of carboxyl-functionalized metal-organic framework with binary ligands for highly selective enrichment of N-linked glycopeptides. 28842020 4 27 theme practical 770:778 arg1 samples 791:797 practical biological samples 770:797 practical biological samples 770:797 The as-prepared material demonstrated excellent performance for selective enrichment of glycopeptides from tryptic digests of standard glycoproteins and practical biological samples. 28842020 0 28 theme framework 60:68 arg1 synthesis 9:17 One-step synthesis 0:17 One-step synthesis of carboxyl-functionalized metal-organic framework with binary ligands for highly selective enrichment of N-linked glycopeptides. 0:147 One-step synthesis of carboxyl-functionalized metal-organic framework with binary ligands for highly selective enrichment of N-linked glycopeptides. 28842020 4 29 theme biological 780:789 arg1 samples 791:797 practical biological samples 770:797 practical biological samples 770:797 The as-prepared material demonstrated excellent performance for selective enrichment of glycopeptides from tryptic digests of standard glycoproteins and practical biological samples. 28842020 4 30 theme tryptic 724:730 arg1 digests 732:738 tryptic digests 724:738 tryptic digests of standard glycoproteins and practical biological samples 724:797 The as-prepared material demonstrated excellent performance for selective enrichment of glycopeptides from tryptic digests of standard glycoproteins and practical biological samples. 28842020 0 31 theme metal-organic 46:58 arg1 framework 60:68 carboxyl-functionalized metal-organic framework 22:68 carboxyl-functionalized metal-organic framework 22:68 One-step synthesis of carboxyl-functionalized metal-organic framework with binary ligands for highly selective enrichment of N-linked glycopeptides. 28842020 3 32 contain containing 487:496 arg1 UiO-66-COOH 475:485 UiO-66-COOH 475:485 UiO-66-COOH containing binary ligands 475:511 Compared with pure UiO-66 with one ligand, UiO-66-COOH containing binary ligands demonstrated greater hydrophilicity and performed much better in selective enrichment of glycopeptides. 28842020 3 32 contain containing 487:496 arg2 ligands 505:511 binary ligands 498:511 binary ligands 498:511 Compared with pure UiO-66 with one ligand, UiO-66-COOH containing binary ligands demonstrated greater hydrophilicity and performed much better in selective enrichment of glycopeptides. 28842020 1 33 theme mass 250:253 arg1 analysis 268:275 mass spectrometry analysis 250:275 mass spectrometry analysis 250:275 Highly efficient and selective enrichment of glycopeptides from complex biosamples is vital prior to mass spectrometry analysis. 28842020 0 34 theme binary 75:80 arg1 ligands 82:88 binary ligands 75:88 binary ligands for highly selective enrichment of N-linked glycopeptides 75:146 One-step synthesis of carboxyl-functionalized metal-organic framework with binary ligands for highly selective enrichment of N-linked glycopeptides. 28842020 3 35 theme binary 498:503 arg1 ligands 505:511 binary ligands 498:511 binary ligands 498:511 Compared with pure UiO-66 with one ligand, UiO-66-COOH containing binary ligands demonstrated greater hydrophilicity and performed much better in selective enrichment of glycopeptides. 28842020 0 36 with synthesis 9:17 arg1 ligands 82:88 binary ligands 75:88 binary ligands for highly selective enrichment of N-linked glycopeptides 75:146 One-step synthesis of carboxyl-functionalized metal-organic framework with binary ligands for highly selective enrichment of N-linked glycopeptides. 28842020 3 37 theme greater 526:532 arg1 hydrophilicity 534:547 greater hydrophilicity 526:547 greater hydrophilicity 526:547 Compared with pure UiO-66 with one ligand, UiO-66-COOH containing binary ligands demonstrated greater hydrophilicity and performed much better in selective enrichment of glycopeptides. 28842020 1 38 gly glycopeptides 194:206 arg2 glycopeptides 194:206 glycopeptides 194:206 glycopeptides 194:206 Highly efficient and selective enrichment of glycopeptides from complex biosamples is vital prior to mass spectrometry analysis. 28842020 1 39 theme efficient 156:164 arg1 enrichment 180:189 Highly efficient and selective enrichment 149:189 Highly efficient and selective enrichment of glycopeptides from complex biosamples 149:230 Highly efficient and selective enrichment of glycopeptides from complex biosamples is vital prior to mass spectrometry analysis. 28842020 3 40 gly glycopeptides 602:614 arg2 glycopeptides 602:614 glycopeptides 602:614 glycopeptides 602:614 Compared with pure UiO-66 with one ligand, UiO-66-COOH containing binary ligands demonstrated greater hydrophilicity and performed much better in selective enrichment of glycopeptides. 28842020 1 41 theme spectrometry 255:266 arg1 analysis 268:275 mass spectrometry analysis 250:275 mass spectrometry analysis 250:275 Highly efficient and selective enrichment of glycopeptides from complex biosamples is vital prior to mass spectrometry analysis. 28842020 1 42 from biosamples 221:230 arg1 enrichment 180:189 Highly efficient and selective enrichment 149:189 Highly efficient and selective enrichment of glycopeptides from complex biosamples 149:230 Highly efficient and selective enrichment of glycopeptides from complex biosamples is vital prior to mass spectrometry analysis. 28842020 2 43 dep groups 351:356 arg1 denoted 359:365 denoted 359:365 denoted as UiO-66-COOH 359:380 In this work, a hydrophilic metal organic framework with free carboxylic groups (denoted as UiO-66-COOH) was synthesized in one step with binary ligands. 28842020 0 44 link N-linked 125:132 arg1 glycopeptides 134:146 N-linked glycopeptides 125:146 N-linked glycopeptides 125:146 One-step synthesis of carboxyl-functionalized metal-organic framework with binary ligands for highly selective enrichment of N-linked glycopeptides. 28842020 1 45 theme selective 170:178 arg1 enrichment 180:189 Highly efficient and selective enrichment 149:189 Highly efficient and selective enrichment of glycopeptides from complex biosamples 149:230 Highly efficient and selective enrichment of glycopeptides from complex biosamples is vital prior to mass spectrometry analysis. 28842020 2 46 with framework 320:328 arg1 groups 351:356 free carboxylic groups 335:356 free carboxylic groups (denoted as UiO-66-COOH) 335:381 In this work, a hydrophilic metal organic framework with free carboxylic groups (denoted as UiO-66-COOH) was synthesized in one step with binary ligands. 28842020 2 47 with step 406:409 arg1 ligands 423:429 binary ligands 416:429 binary ligands 416:429 In this work, a hydrophilic metal organic framework with free carboxylic groups (denoted as UiO-66-COOH) was synthesized in one step with binary ligands. 28842020 4 48 theme selective 681:689 arg1 enrichment 691:700 selective enrichment 681:700 selective enrichment of glycopeptides from tryptic digests of standard glycoproteins and practical biological samples 681:797 The as-prepared material demonstrated excellent performance for selective enrichment of glycopeptides from tryptic digests of standard glycoproteins and practical biological samples. 27144524 4 0 with interaction 1102:1112 arg1 number 1121:1126 a number 1119:1126 a number of miRNAs regulating spine restructuring 1119:1167 These responses may be epigenetically modulated by the interaction with a number of miRNAs regulating spine restructuring, Aβ expression and neuroinflammation.We suggest that these changes could be associated with development of cognitive dysfunction in early disease states in patients with Alzheimer's disease. 27144524 3 1 theme argyrophilic 941:952 arg1 structures 966:975 argyrophilic tangle-like structures 941:975 argyrophilic tangle-like structures 941:975 This was associated with cerebral amyloidosis as well as formation of argyrophilic tangle-like structures and microglial clustering in all brain regions, except for brainstem. 27144524 1 2 theme APPswe/PS1ΔE9 241:253 arg1 model 276:280 a widely used model 262:280 a widely used model of cerebral amyloidosis 262:304 The aim of this study was to elucidate the molecular signature of Alzheimer's disease-associated amyloid pathology.We used the double APPswe/PS1ΔE9 mouse, a widely used model of cerebral amyloidosis, to compare changes in proteome, including global phosphorylation and sialylated N-linked glycosylation patterns, pathway-focused transcriptome and neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem. 27144524 1 2 theme APPswe/PS1ΔE9 241:253 arg1 mouse 255:259 the double APPswe/PS1ΔE9 mouse 230:259 the double APPswe/PS1ΔE9 mouse 230:259 The aim of this study was to elucidate the molecular signature of Alzheimer's disease-associated amyloid pathology.We used the double APPswe/PS1ΔE9 mouse, a widely used model of cerebral amyloidosis, to compare changes in proteome, including global phosphorylation and sialylated N-linked glycosylation patterns, pathway-focused transcriptome and neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem. 27144524 0 3 theme APP/PS1 74:80 arg1 Alzheimer 82:90 APP/PS1 Alzheimer's 74:92 an APP/PS1 Alzheimer's mouse model 71:104 An integrated proteomics approach shows synaptic plasticity changes in an APP/PS1 Alzheimer's mouse model. 27144524 2 4 theme long-term 706:714 arg1 potentiation 716:727 long-term potentiation 706:727 long-term potentiation 706:727 We report that signalling pathways related to synaptic functions associated with dendritic spine morphology, neurite outgrowth, long-term potentiation, CREB signalling and cytoskeletal dynamics were altered in 12 month old APPswe/PS1ΔE9 mice, particularly in the neocortex and olfactory bulb. 27144524 4 5 theme miRNAs 1131:1136 arg1 number 1121:1126 a number 1119:1126 a number of miRNAs regulating spine restructuring 1119:1167 These responses may be epigenetically modulated by the interaction with a number of miRNAs regulating spine restructuring, Aβ expression and neuroinflammation.We suggest that these changes could be associated with development of cognitive dysfunction in early disease states in patients with Alzheimer's disease. 27144524 0 6 theme mouse 94:98 arg1 model 100:104 an APP/PS1 Alzheimer's mouse model 71:104 an APP/PS1 Alzheimer's mouse model 71:104 An integrated proteomics approach shows synaptic plasticity changes in an APP/PS1 Alzheimer's mouse model. 27144524 2 7 theme CREB 730:733 arg1 signalling 735:744 CREB signalling 730:744 CREB signalling 730:744 We report that signalling pathways related to synaptic functions associated with dendritic spine morphology, neurite outgrowth, long-term potentiation, CREB signalling and cytoskeletal dynamics were altered in 12 month old APPswe/PS1ΔE9 mice, particularly in the neocortex and olfactory bulb. 27144524 1 8 theme neurological 454:465 arg1 miRNAome 486:493 neurological disease-associated miRNAome 454:493 neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem 454:575 The aim of this study was to elucidate the molecular signature of Alzheimer's disease-associated amyloid pathology.We used the double APPswe/PS1ΔE9 mouse, a widely used model of cerebral amyloidosis, to compare changes in proteome, including global phosphorylation and sialylated N-linked glycosylation patterns, pathway-focused transcriptome and neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem. 27144524 1 8 theme neurological 454:465 arg1 patterns 410:417 sialylated N-linked glycosylation patterns 376:417 sialylated N-linked glycosylation patterns 376:417 The aim of this study was to elucidate the molecular signature of Alzheimer's disease-associated amyloid pathology.We used the double APPswe/PS1ΔE9 mouse, a widely used model of cerebral amyloidosis, to compare changes in proteome, including global phosphorylation and sialylated N-linked glycosylation patterns, pathway-focused transcriptome and neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem. 27144524 1 9 with miRNAome 486:493 arg1 controls 512:519 age-matched controls 500:519 age-matched controls 500:519 The aim of this study was to elucidate the molecular signature of Alzheimer's disease-associated amyloid pathology.We used the double APPswe/PS1ΔE9 mouse, a widely used model of cerebral amyloidosis, to compare changes in proteome, including global phosphorylation and sialylated N-linked glycosylation patterns, pathway-focused transcriptome and neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem. 27144524 2 10 theme month 791:795 arg1 mice 815:818 12 month old APPswe/PS1ΔE9 mice 788:818 12 month old APPswe/PS1ΔE9 mice 788:818 We report that signalling pathways related to synaptic functions associated with dendritic spine morphology, neurite outgrowth, long-term potentiation, CREB signalling and cytoskeletal dynamics were altered in 12 month old APPswe/PS1ΔE9 mice, particularly in the neocortex and olfactory bulb. 27144524 2 11 theme synaptic 624:631 arg1 functions 633:641 synaptic functions 624:641 synaptic functions associated with dendritic spine morphology, neurite outgrowth, long-term potentiation, CREB signalling and cytoskeletal dynamics 624:770 We report that signalling pathways related to synaptic functions associated with dendritic spine morphology, neurite outgrowth, long-term potentiation, CREB signalling and cytoskeletal dynamics were altered in 12 month old APPswe/PS1ΔE9 mice, particularly in the neocortex and olfactory bulb. 27144524 1 12 theme disease-associated 467:484 arg1 miRNAome 486:493 neurological disease-associated miRNAome 454:493 neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem 454:575 The aim of this study was to elucidate the molecular signature of Alzheimer's disease-associated amyloid pathology.We used the double APPswe/PS1ΔE9 mouse, a widely used model of cerebral amyloidosis, to compare changes in proteome, including global phosphorylation and sialylated N-linked glycosylation patterns, pathway-focused transcriptome and neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem. 27144524 1 12 theme disease-associated 467:484 arg1 patterns 410:417 sialylated N-linked glycosylation patterns 376:417 sialylated N-linked glycosylation patterns 376:417 The aim of this study was to elucidate the molecular signature of Alzheimer's disease-associated amyloid pathology.We used the double APPswe/PS1ΔE9 mouse, a widely used model of cerebral amyloidosis, to compare changes in proteome, including global phosphorylation and sialylated N-linked glycosylation patterns, pathway-focused transcriptome and neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem. 27144524 3 13 theme cerebral 896:903 arg1 amyloidosis 905:915 cerebral amyloidosis 896:915 cerebral amyloidosis as well as formation of argyrophilic tangle-like structures and microglial clustering in all brain regions, except for brainstem 896:1044 This was associated with cerebral amyloidosis as well as formation of argyrophilic tangle-like structures and microglial clustering in all brain regions, except for brainstem. 27144524 3 14 theme structures 966:975 arg1 formation 928:936 formation 928:936 cerebral amyloidosis as well as formation of argyrophilic tangle-like structures and microglial clustering in all brain regions, except for brainstem 896:1044 This was associated with cerebral amyloidosis as well as formation of argyrophilic tangle-like structures and microglial clustering in all brain regions, except for brainstem. 27144524 3 14 theme structures 966:975 arg1 amyloidosis 905:915 cerebral amyloidosis 896:915 cerebral amyloidosis as well as formation of argyrophilic tangle-like structures and microglial clustering in all brain regions, except for brainstem 896:1044 This was associated with cerebral amyloidosis as well as formation of argyrophilic tangle-like structures and microglial clustering in all brain regions, except for brainstem. 27144524 2 15 theme neurite 687:693 arg1 outgrowth 695:703 neurite outgrowth 687:703 neurite outgrowth 687:703 We report that signalling pathways related to synaptic functions associated with dendritic spine morphology, neurite outgrowth, long-term potentiation, CREB signalling and cytoskeletal dynamics were altered in 12 month old APPswe/PS1ΔE9 mice, particularly in the neocortex and olfactory bulb. 27144524 1 16 with transcriptome 436:448 arg1 controls 512:519 age-matched controls 500:519 age-matched controls 500:519 The aim of this study was to elucidate the molecular signature of Alzheimer's disease-associated amyloid pathology.We used the double APPswe/PS1ΔE9 mouse, a widely used model of cerebral amyloidosis, to compare changes in proteome, including global phosphorylation and sialylated N-linked glycosylation patterns, pathway-focused transcriptome and neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem. 27144524 1 17 theme global 349:354 arg1 phosphorylation 356:370 global phosphorylation 349:370 global phosphorylation 349:370 The aim of this study was to elucidate the molecular signature of Alzheimer's disease-associated amyloid pathology.We used the double APPswe/PS1ΔE9 mouse, a widely used model of cerebral amyloidosis, to compare changes in proteome, including global phosphorylation and sialylated N-linked glycosylation patterns, pathway-focused transcriptome and neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem. 27144524 4 18 theme early 1301:1305 arg1 states 1315:1320 early disease states 1301:1320 early disease states in patients with Alzheimer's disease 1301:1357 These responses may be epigenetically modulated by the interaction with a number of miRNAs regulating spine restructuring, Aβ expression and neuroinflammation.We suggest that these changes could be associated with development of cognitive dysfunction in early disease states in patients with Alzheimer's disease. 27144524 2 19 theme APPswe/PS1ΔE9 801:813 arg1 mice 815:818 12 month old APPswe/PS1ΔE9 mice 788:818 12 month old APPswe/PS1ΔE9 mice 788:818 We report that signalling pathways related to synaptic functions associated with dendritic spine morphology, neurite outgrowth, long-term potentiation, CREB signalling and cytoskeletal dynamics were altered in 12 month old APPswe/PS1ΔE9 mice, particularly in the neocortex and olfactory bulb. 27144524 1 20 theme molecular 150:158 arg1 signature 160:168 the molecular signature 146:168 the molecular signature of Alzheimer's disease-associated amyloid pathology.We used the double APPswe/PS1ΔE9 mouse, a widely used model of cerebral amyloidosis, to compare changes in proteome, including global phosphorylation and sialylated N-linked glycosylation patterns, pathway-focused transcriptome and neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem 146:575 The aim of this study was to elucidate the molecular signature of Alzheimer's disease-associated amyloid pathology.We used the double APPswe/PS1ΔE9 mouse, a widely used model of cerebral amyloidosis, to compare changes in proteome, including global phosphorylation and sialylated N-linked glycosylation patterns, pathway-focused transcriptome and neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem. 27144524 0 21 theme integrated 3:12 arg1 approach 25:32 An integrated proteomics approach 0:32 An integrated proteomics approach 0:32 An integrated proteomics approach shows synaptic plasticity changes in an APP/PS1 Alzheimer's mouse model. 27144524 2 22 theme spine 669:673 arg1 morphology 675:684 dendritic spine morphology 659:684 dendritic spine morphology 659:684 We report that signalling pathways related to synaptic functions associated with dendritic spine morphology, neurite outgrowth, long-term potentiation, CREB signalling and cytoskeletal dynamics were altered in 12 month old APPswe/PS1ΔE9 mice, particularly in the neocortex and olfactory bulb. 27144524 1 23 theme age-matched 500:510 arg1 controls 512:519 age-matched controls 500:519 age-matched controls 500:519 The aim of this study was to elucidate the molecular signature of Alzheimer's disease-associated amyloid pathology.We used the double APPswe/PS1ΔE9 mouse, a widely used model of cerebral amyloidosis, to compare changes in proteome, including global phosphorylation and sialylated N-linked glycosylation patterns, pathway-focused transcriptome and neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem. 27144524 4 24 from states 1315:1320 arg1 patients 1325:1332 patients 1325:1332 patients with Alzheimer's disease 1325:1357 These responses may be epigenetically modulated by the interaction with a number of miRNAs regulating spine restructuring, Aβ expression and neuroinflammation.We suggest that these changes could be associated with development of cognitive dysfunction in early disease states in patients with Alzheimer's disease. 27144524 4 24 from states 1315:1320 arg1 development 1261:1271 development 1261:1271 development of cognitive dysfunction in early disease states in patients with Alzheimer's disease 1261:1357 These responses may be epigenetically modulated by the interaction with a number of miRNAs regulating spine restructuring, Aβ expression and neuroinflammation.We suggest that these changes could be associated with development of cognitive dysfunction in early disease states in patients with Alzheimer's disease. 27144524 2 25 theme old 797:799 arg1 mice 815:818 12 month old APPswe/PS1ΔE9 mice 788:818 12 month old APPswe/PS1ΔE9 mice 788:818 We report that signalling pathways related to synaptic functions associated with dendritic spine morphology, neurite outgrowth, long-term potentiation, CREB signalling and cytoskeletal dynamics were altered in 12 month old APPswe/PS1ΔE9 mice, particularly in the neocortex and olfactory bulb. 27144524 2 26 theme dendritic 659:667 arg1 morphology 675:684 dendritic spine morphology 659:684 dendritic spine morphology 659:684 We report that signalling pathways related to synaptic functions associated with dendritic spine morphology, neurite outgrowth, long-term potentiation, CREB signalling and cytoskeletal dynamics were altered in 12 month old APPswe/PS1ΔE9 mice, particularly in the neocortex and olfactory bulb. 27144524 3 27 from amyloidosis 905:915 arg1 regions 1016:1022 all brain regions 1006:1022 all brain regions 1006:1022 This was associated with cerebral amyloidosis as well as formation of argyrophilic tangle-like structures and microglial clustering in all brain regions, except for brainstem. 27144524 1 28 theme used 271:274 arg1 model 276:280 a widely used model 262:280 a widely used model of cerebral amyloidosis 262:304 The aim of this study was to elucidate the molecular signature of Alzheimer's disease-associated amyloid pathology.We used the double APPswe/PS1ΔE9 mouse, a widely used model of cerebral amyloidosis, to compare changes in proteome, including global phosphorylation and sialylated N-linked glycosylation patterns, pathway-focused transcriptome and neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem. 27144524 1 28 theme used 271:274 arg1 mouse 255:259 the double APPswe/PS1ΔE9 mouse 230:259 the double APPswe/PS1ΔE9 mouse 230:259 The aim of this study was to elucidate the molecular signature of Alzheimer's disease-associated amyloid pathology.We used the double APPswe/PS1ΔE9 mouse, a widely used model of cerebral amyloidosis, to compare changes in proteome, including global phosphorylation and sialylated N-linked glycosylation patterns, pathway-focused transcriptome and neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem. 27144524 4 29 theme disease 1307:1313 arg1 states 1315:1320 early disease states 1301:1320 early disease states in patients with Alzheimer's disease 1301:1357 These responses may be epigenetically modulated by the interaction with a number of miRNAs regulating spine restructuring, Aβ expression and neuroinflammation.We suggest that these changes could be associated with development of cognitive dysfunction in early disease states in patients with Alzheimer's disease. 27144524 3 30 theme brain 1010:1014 arg1 regions 1016:1022 all brain regions 1006:1022 all brain regions 1006:1022 This was associated with cerebral amyloidosis as well as formation of argyrophilic tangle-like structures and microglial clustering in all brain regions, except for brainstem. 27144524 0 31 theme proteomics 14:23 arg1 approach 25:32 An integrated proteomics approach 0:32 An integrated proteomics approach 0:32 An integrated proteomics approach shows synaptic plasticity changes in an APP/PS1 Alzheimer's mouse model. 27144524 2 32 dep neocortex 841:849 arg1 the 837:839 the 837:839 the 837:839 We report that signalling pathways related to synaptic functions associated with dendritic spine morphology, neurite outgrowth, long-term potentiation, CREB signalling and cytoskeletal dynamics were altered in 12 month old APPswe/PS1ΔE9 mice, particularly in the neocortex and olfactory bulb. 27144524 3 33 theme clustering 992:1001 arg1 formation 928:936 formation 928:936 cerebral amyloidosis as well as formation of argyrophilic tangle-like structures and microglial clustering in all brain regions, except for brainstem 896:1044 This was associated with cerebral amyloidosis as well as formation of argyrophilic tangle-like structures and microglial clustering in all brain regions, except for brainstem. 27144524 3 33 theme clustering 992:1001 arg1 amyloidosis 905:915 cerebral amyloidosis 896:915 cerebral amyloidosis as well as formation of argyrophilic tangle-like structures and microglial clustering in all brain regions, except for brainstem 896:1044 This was associated with cerebral amyloidosis as well as formation of argyrophilic tangle-like structures and microglial clustering in all brain regions, except for brainstem. 27144524 0 34 theme synaptic 40:47 arg1 plasticity 49:58 synaptic plasticity changes 40:66 synaptic plasticity changes 40:66 An integrated proteomics approach shows synaptic plasticity changes in an APP/PS1 Alzheimer's mouse model. 27144524 3 35 theme microglial 981:990 arg1 clustering 992:1001 microglial clustering 981:1001 microglial clustering 981:1001 This was associated with cerebral amyloidosis as well as formation of argyrophilic tangle-like structures and microglial clustering in all brain regions, except for brainstem. 27144524 1 36 theme sialylated 376:385 arg1 miRNAome 486:493 neurological disease-associated miRNAome 454:493 neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem 454:575 The aim of this study was to elucidate the molecular signature of Alzheimer's disease-associated amyloid pathology.We used the double APPswe/PS1ΔE9 mouse, a widely used model of cerebral amyloidosis, to compare changes in proteome, including global phosphorylation and sialylated N-linked glycosylation patterns, pathway-focused transcriptome and neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem. 27144524 1 36 theme sialylated 376:385 arg1 patterns 410:417 sialylated N-linked glycosylation patterns 376:417 sialylated N-linked glycosylation patterns 376:417 The aim of this study was to elucidate the molecular signature of Alzheimer's disease-associated amyloid pathology.We used the double APPswe/PS1ΔE9 mouse, a widely used model of cerebral amyloidosis, to compare changes in proteome, including global phosphorylation and sialylated N-linked glycosylation patterns, pathway-focused transcriptome and neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem. 27144524 1 36 theme sialylated 376:385 arg1 transcriptome 436:448 pathway-focused transcriptome 420:448 pathway-focused transcriptome 420:448 The aim of this study was to elucidate the molecular signature of Alzheimer's disease-associated amyloid pathology.We used the double APPswe/PS1ΔE9 mouse, a widely used model of cerebral amyloidosis, to compare changes in proteome, including global phosphorylation and sialylated N-linked glycosylation patterns, pathway-focused transcriptome and neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem. 27144524 4 37 from dysfunction 1286:1296 arg1 states 1315:1320 early disease states 1301:1320 early disease states in patients with Alzheimer's disease 1301:1357 These responses may be epigenetically modulated by the interaction with a number of miRNAs regulating spine restructuring, Aβ expression and neuroinflammation.We suggest that these changes could be associated with development of cognitive dysfunction in early disease states in patients with Alzheimer's disease. 27144524 3 38 from formation 928:936 arg1 regions 1016:1022 all brain regions 1006:1022 all brain regions 1006:1022 This was associated with cerebral amyloidosis as well as formation of argyrophilic tangle-like structures and microglial clustering in all brain regions, except for brainstem. 27144524 1 39 theme disease-associated 185:202 arg1 amyloid 204:210 Alzheimer's disease-associated amyloid 173:210 Alzheimer's disease-associated amyloid pathology.We used the double APPswe/PS1ΔE9 mouse, a widely used model of cerebral amyloidosis, to compare changes in proteome, including global phosphorylation and sialylated N-linked glycosylation patterns, pathway-focused transcriptome and neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem 173:575 The aim of this study was to elucidate the molecular signature of Alzheimer's disease-associated amyloid pathology.We used the double APPswe/PS1ΔE9 mouse, a widely used model of cerebral amyloidosis, to compare changes in proteome, including global phosphorylation and sialylated N-linked glycosylation patterns, pathway-focused transcriptome and neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem. 27144524 4 40 theme spine 1149:1153 arg1 restructuring 1155:1167 spine restructuring 1149:1167 spine restructuring 1149:1167 These responses may be epigenetically modulated by the interaction with a number of miRNAs regulating spine restructuring, Aβ expression and neuroinflammation.We suggest that these changes could be associated with development of cognitive dysfunction in early disease states in patients with Alzheimer's disease. 27144524 1 41 theme cerebral 285:292 arg1 amyloidosis 294:304 cerebral amyloidosis 285:304 cerebral amyloidosis 285:304 The aim of this study was to elucidate the molecular signature of Alzheimer's disease-associated amyloid pathology.We used the double APPswe/PS1ΔE9 mouse, a widely used model of cerebral amyloidosis, to compare changes in proteome, including global phosphorylation and sialylated N-linked glycosylation patterns, pathway-focused transcriptome and neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem. 27144524 1 42 theme N-linked 387:394 arg1 glycosylation 396:408 N-linked glycosylation 387:408 sialylated N-linked glycosylation patterns 376:417 The aim of this study was to elucidate the molecular signature of Alzheimer's disease-associated amyloid pathology.We used the double APPswe/PS1ΔE9 mouse, a widely used model of cerebral amyloidosis, to compare changes in proteome, including global phosphorylation and sialylated N-linked glycosylation patterns, pathway-focused transcriptome and neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem. 27144524 0 43 dep plasticity 49:58 arg1 changes 60:66 changes 60:66 changes 60:66 An integrated proteomics approach shows synaptic plasticity changes in an APP/PS1 Alzheimer's mouse model. 27144524 1 44 theme amyloidosis 294:304 arg1 model 276:280 a widely used model 262:280 a widely used model of cerebral amyloidosis 262:304 The aim of this study was to elucidate the molecular signature of Alzheimer's disease-associated amyloid pathology.We used the double APPswe/PS1ΔE9 mouse, a widely used model of cerebral amyloidosis, to compare changes in proteome, including global phosphorylation and sialylated N-linked glycosylation patterns, pathway-focused transcriptome and neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem. 27144524 1 44 theme amyloidosis 294:304 arg1 mouse 255:259 the double APPswe/PS1ΔE9 mouse 230:259 the double APPswe/PS1ΔE9 mouse 230:259 The aim of this study was to elucidate the molecular signature of Alzheimer's disease-associated amyloid pathology.We used the double APPswe/PS1ΔE9 mouse, a widely used model of cerebral amyloidosis, to compare changes in proteome, including global phosphorylation and sialylated N-linked glycosylation patterns, pathway-focused transcriptome and neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem. 27144524 1 45 theme glycosylation 396:408 arg1 miRNAome 486:493 neurological disease-associated miRNAome 454:493 neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem 454:575 The aim of this study was to elucidate the molecular signature of Alzheimer's disease-associated amyloid pathology.We used the double APPswe/PS1ΔE9 mouse, a widely used model of cerebral amyloidosis, to compare changes in proteome, including global phosphorylation and sialylated N-linked glycosylation patterns, pathway-focused transcriptome and neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem. 27144524 1 45 theme glycosylation 396:408 arg1 patterns 410:417 sialylated N-linked glycosylation patterns 376:417 sialylated N-linked glycosylation patterns 376:417 The aim of this study was to elucidate the molecular signature of Alzheimer's disease-associated amyloid pathology.We used the double APPswe/PS1ΔE9 mouse, a widely used model of cerebral amyloidosis, to compare changes in proteome, including global phosphorylation and sialylated N-linked glycosylation patterns, pathway-focused transcriptome and neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem. 27144524 1 45 theme glycosylation 396:408 arg1 transcriptome 436:448 pathway-focused transcriptome 420:448 pathway-focused transcriptome 420:448 The aim of this study was to elucidate the molecular signature of Alzheimer's disease-associated amyloid pathology.We used the double APPswe/PS1ΔE9 mouse, a widely used model of cerebral amyloidosis, to compare changes in proteome, including global phosphorylation and sialylated N-linked glycosylation patterns, pathway-focused transcriptome and neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem. 27144524 1 46 from changes 318:324 arg1 proteome 329:336 proteome 329:336 proteome 329:336 The aim of this study was to elucidate the molecular signature of Alzheimer's disease-associated amyloid pathology.We used the double APPswe/PS1ΔE9 mouse, a widely used model of cerebral amyloidosis, to compare changes in proteome, including global phosphorylation and sialylated N-linked glycosylation patterns, pathway-focused transcriptome and neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem. 27144524 2 47 theme related 613:619 arg1 pathways 604:611 signalling pathways 593:611 signalling pathways related to synaptic functions associated with dendritic spine morphology, neurite outgrowth, long-term potentiation, CREB signalling and cytoskeletal dynamics 593:770 We report that signalling pathways related to synaptic functions associated with dendritic spine morphology, neurite outgrowth, long-term potentiation, CREB signalling and cytoskeletal dynamics were altered in 12 month old APPswe/PS1ΔE9 mice, particularly in the neocortex and olfactory bulb. 27144524 4 48 from development 1261:1271 arg1 states 1315:1320 early disease states 1301:1320 early disease states in patients with Alzheimer's disease 1301:1357 These responses may be epigenetically modulated by the interaction with a number of miRNAs regulating spine restructuring, Aβ expression and neuroinflammation.We suggest that these changes could be associated with development of cognitive dysfunction in early disease states in patients with Alzheimer's disease. 27144524 2 49 theme cytoskeletal 750:761 arg1 dynamics 763:770 cytoskeletal dynamics 750:770 cytoskeletal dynamics 750:770 We report that signalling pathways related to synaptic functions associated with dendritic spine morphology, neurite outgrowth, long-term potentiation, CREB signalling and cytoskeletal dynamics were altered in 12 month old APPswe/PS1ΔE9 mice, particularly in the neocortex and olfactory bulb. 27144524 1 50 dep pathology.We 212:223 arg1 used 225:228 used 225:228 pathology.We used the double APPswe/PS1ΔE9 mouse, a widely used model of cerebral amyloidosis, to compare changes in proteome, including global phosphorylation and sialylated N-linked glycosylation patterns, pathway-focused transcriptome and neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem 212:575 The aim of this study was to elucidate the molecular signature of Alzheimer's disease-associated amyloid pathology.We used the double APPswe/PS1ΔE9 mouse, a widely used model of cerebral amyloidosis, to compare changes in proteome, including global phosphorylation and sialylated N-linked glycosylation patterns, pathway-focused transcriptome and neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem. 27144524 1 51 gly sialylated 376:385 arg1 miRNAome 486:493 neurological disease-associated miRNAome 454:493 neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem 454:575 The aim of this study was to elucidate the molecular signature of Alzheimer's disease-associated amyloid pathology.We used the double APPswe/PS1ΔE9 mouse, a widely used model of cerebral amyloidosis, to compare changes in proteome, including global phosphorylation and sialylated N-linked glycosylation patterns, pathway-focused transcriptome and neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem. 27144524 1 51 gly sialylated 376:385 arg1 patterns 410:417 sialylated N-linked glycosylation patterns 376:417 sialylated N-linked glycosylation patterns 376:417 The aim of this study was to elucidate the molecular signature of Alzheimer's disease-associated amyloid pathology.We used the double APPswe/PS1ΔE9 mouse, a widely used model of cerebral amyloidosis, to compare changes in proteome, including global phosphorylation and sialylated N-linked glycosylation patterns, pathway-focused transcriptome and neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem. 27144524 1 51 gly sialylated 376:385 arg1 transcriptome 436:448 pathway-focused transcriptome 420:448 pathway-focused transcriptome 420:448 The aim of this study was to elucidate the molecular signature of Alzheimer's disease-associated amyloid pathology.We used the double APPswe/PS1ΔE9 mouse, a widely used model of cerebral amyloidosis, to compare changes in proteome, including global phosphorylation and sialylated N-linked glycosylation patterns, pathway-focused transcriptome and neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem. 27144524 4 52 theme cognitive 1276:1284 arg1 dysfunction 1286:1296 cognitive dysfunction 1276:1296 cognitive dysfunction in early disease states in patients with Alzheimer's disease 1276:1357 These responses may be epigenetically modulated by the interaction with a number of miRNAs regulating spine restructuring, Aβ expression and neuroinflammation.We suggest that these changes could be associated with development of cognitive dysfunction in early disease states in patients with Alzheimer's disease. 27144524 4 53 theme dysfunction 1286:1296 arg1 development 1261:1271 development 1261:1271 development of cognitive dysfunction in early disease states in patients with Alzheimer's disease 1261:1357 These responses may be epigenetically modulated by the interaction with a number of miRNAs regulating spine restructuring, Aβ expression and neuroinflammation.We suggest that these changes could be associated with development of cognitive dysfunction in early disease states in patients with Alzheimer's disease. 27144524 2 54 theme signalling 593:602 arg1 pathways 604:611 signalling pathways 593:611 signalling pathways related to synaptic functions associated with dendritic spine morphology, neurite outgrowth, long-term potentiation, CREB signalling and cytoskeletal dynamics 593:770 We report that signalling pathways related to synaptic functions associated with dendritic spine morphology, neurite outgrowth, long-term potentiation, CREB signalling and cytoskeletal dynamics were altered in 12 month old APPswe/PS1ΔE9 mice, particularly in the neocortex and olfactory bulb. 27144524 1 55 theme pathway-focused 420:434 arg1 patterns 410:417 sialylated N-linked glycosylation patterns 376:417 sialylated N-linked glycosylation patterns 376:417 The aim of this study was to elucidate the molecular signature of Alzheimer's disease-associated amyloid pathology.We used the double APPswe/PS1ΔE9 mouse, a widely used model of cerebral amyloidosis, to compare changes in proteome, including global phosphorylation and sialylated N-linked glycosylation patterns, pathway-focused transcriptome and neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem. 27144524 1 55 theme pathway-focused 420:434 arg1 transcriptome 436:448 pathway-focused transcriptome 420:448 pathway-focused transcriptome 420:448 The aim of this study was to elucidate the molecular signature of Alzheimer's disease-associated amyloid pathology.We used the double APPswe/PS1ΔE9 mouse, a widely used model of cerebral amyloidosis, to compare changes in proteome, including global phosphorylation and sialylated N-linked glycosylation patterns, pathway-focused transcriptome and neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem. 27144524 1 56 theme olfactory 548:556 arg1 bulb 558:561 olfactory bulb 548:561 olfactory bulb 548:561 The aim of this study was to elucidate the molecular signature of Alzheimer's disease-associated amyloid pathology.We used the double APPswe/PS1ΔE9 mouse, a widely used model of cerebral amyloidosis, to compare changes in proteome, including global phosphorylation and sialylated N-linked glycosylation patterns, pathway-focused transcriptome and neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem. 27144524 4 57 theme Aβ 1170:1171 arg1 expression 1173:1182 Aβ expression 1170:1182 Aβ expression 1170:1182 These responses may be epigenetically modulated by the interaction with a number of miRNAs regulating spine restructuring, Aβ expression and neuroinflammation.We suggest that these changes could be associated with development of cognitive dysfunction in early disease states in patients with Alzheimer's disease. 27144524 2 58 theme olfactory 855:863 arg1 bulb 865:868 olfactory bulb 855:868 olfactory bulb 855:868 We report that signalling pathways related to synaptic functions associated with dendritic spine morphology, neurite outgrowth, long-term potentiation, CREB signalling and cytoskeletal dynamics were altered in 12 month old APPswe/PS1ΔE9 mice, particularly in the neocortex and olfactory bulb. 27144524 3 59 theme tangle-like 954:964 arg1 structures 966:975 argyrophilic tangle-like structures 941:975 argyrophilic tangle-like structures 941:975 This was associated with cerebral amyloidosis as well as formation of argyrophilic tangle-like structures and microglial clustering in all brain regions, except for brainstem. 27144524 2 60 theme 12 788:789 arg1 month 791:795 month 791:795 month 791:795 We report that signalling pathways related to synaptic functions associated with dendritic spine morphology, neurite outgrowth, long-term potentiation, CREB signalling and cytoskeletal dynamics were altered in 12 month old APPswe/PS1ΔE9 mice, particularly in the neocortex and olfactory bulb. 27144524 1 61 theme study 123:127 arg1 aim 111:113 The aim 107:113 The aim of this study 107:127 The aim of this study was to elucidate the molecular signature of Alzheimer's disease-associated amyloid pathology.We used the double APPswe/PS1ΔE9 mouse, a widely used model of cerebral amyloidosis, to compare changes in proteome, including global phosphorylation and sialylated N-linked glycosylation patterns, pathway-focused transcriptome and neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem. 27144524 1 62 from transcriptome 436:448 arg1 hippocampus 535:545 hippocampus 535:545 hippocampus 535:545 The aim of this study was to elucidate the molecular signature of Alzheimer's disease-associated amyloid pathology.We used the double APPswe/PS1ΔE9 mouse, a widely used model of cerebral amyloidosis, to compare changes in proteome, including global phosphorylation and sialylated N-linked glycosylation patterns, pathway-focused transcriptome and neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem. 27144524 1 62 from transcriptome 436:448 arg1 bulb 558:561 olfactory bulb 548:561 olfactory bulb 548:561 The aim of this study was to elucidate the molecular signature of Alzheimer's disease-associated amyloid pathology.We used the double APPswe/PS1ΔE9 mouse, a widely used model of cerebral amyloidosis, to compare changes in proteome, including global phosphorylation and sialylated N-linked glycosylation patterns, pathway-focused transcriptome and neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem. 27144524 1 62 from transcriptome 436:448 arg1 neocortex 524:532 neocortex 524:532 neocortex 524:532 The aim of this study was to elucidate the molecular signature of Alzheimer's disease-associated amyloid pathology.We used the double APPswe/PS1ΔE9 mouse, a widely used model of cerebral amyloidosis, to compare changes in proteome, including global phosphorylation and sialylated N-linked glycosylation patterns, pathway-focused transcriptome and neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem. 27144524 1 62 from transcriptome 436:448 arg1 brainstem 567:575 brainstem 567:575 brainstem 567:575 The aim of this study was to elucidate the molecular signature of Alzheimer's disease-associated amyloid pathology.We used the double APPswe/PS1ΔE9 mouse, a widely used model of cerebral amyloidosis, to compare changes in proteome, including global phosphorylation and sialylated N-linked glycosylation patterns, pathway-focused transcriptome and neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem. 27144524 1 63 from miRNAome 486:493 arg1 hippocampus 535:545 hippocampus 535:545 hippocampus 535:545 The aim of this study was to elucidate the molecular signature of Alzheimer's disease-associated amyloid pathology.We used the double APPswe/PS1ΔE9 mouse, a widely used model of cerebral amyloidosis, to compare changes in proteome, including global phosphorylation and sialylated N-linked glycosylation patterns, pathway-focused transcriptome and neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem. 27144524 1 63 from miRNAome 486:493 arg1 bulb 558:561 olfactory bulb 548:561 olfactory bulb 548:561 The aim of this study was to elucidate the molecular signature of Alzheimer's disease-associated amyloid pathology.We used the double APPswe/PS1ΔE9 mouse, a widely used model of cerebral amyloidosis, to compare changes in proteome, including global phosphorylation and sialylated N-linked glycosylation patterns, pathway-focused transcriptome and neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem. 27144524 1 63 from miRNAome 486:493 arg1 neocortex 524:532 neocortex 524:532 neocortex 524:532 The aim of this study was to elucidate the molecular signature of Alzheimer's disease-associated amyloid pathology.We used the double APPswe/PS1ΔE9 mouse, a widely used model of cerebral amyloidosis, to compare changes in proteome, including global phosphorylation and sialylated N-linked glycosylation patterns, pathway-focused transcriptome and neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem. 27144524 1 63 from miRNAome 486:493 arg1 brainstem 567:575 brainstem 567:575 brainstem 567:575 The aim of this study was to elucidate the molecular signature of Alzheimer's disease-associated amyloid pathology.We used the double APPswe/PS1ΔE9 mouse, a widely used model of cerebral amyloidosis, to compare changes in proteome, including global phosphorylation and sialylated N-linked glycosylation patterns, pathway-focused transcriptome and neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem. 27144524 1 64 link N-linked 387:394 arg1 glycosylation 396:408 N-linked glycosylation 387:408 sialylated N-linked glycosylation patterns 376:417 The aim of this study was to elucidate the molecular signature of Alzheimer's disease-associated amyloid pathology.We used the double APPswe/PS1ΔE9 mouse, a widely used model of cerebral amyloidosis, to compare changes in proteome, including global phosphorylation and sialylated N-linked glycosylation patterns, pathway-focused transcriptome and neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem. 27144524 1 65 theme double 234:239 arg1 model 276:280 a widely used model 262:280 a widely used model of cerebral amyloidosis 262:304 The aim of this study was to elucidate the molecular signature of Alzheimer's disease-associated amyloid pathology.We used the double APPswe/PS1ΔE9 mouse, a widely used model of cerebral amyloidosis, to compare changes in proteome, including global phosphorylation and sialylated N-linked glycosylation patterns, pathway-focused transcriptome and neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem. 27144524 1 65 theme double 234:239 arg1 mouse 255:259 the double APPswe/PS1ΔE9 mouse 230:259 the double APPswe/PS1ΔE9 mouse 230:259 The aim of this study was to elucidate the molecular signature of Alzheimer's disease-associated amyloid pathology.We used the double APPswe/PS1ΔE9 mouse, a widely used model of cerebral amyloidosis, to compare changes in proteome, including global phosphorylation and sialylated N-linked glycosylation patterns, pathway-focused transcriptome and neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem. 26388377 3 0 theme glycopeptide 342:353 arg1 level 355:359 the glycopeptide level 338:359 the glycopeptide level 338:359 Studying these molecules at the glycopeptide level however, offers distinct advantages, namely the ability to characterize both the glycan and peptide fragments simultaneously, and moreover the ability to assign site specific heterogeneity. 26388377 10 1 theme liquid 1447:1452 arg1 HILIC 1470:1474 HILIC 1470:1474 HILIC 1470:1474 This corroborated that this stationary phase was exhibiting a mixed-mode enrichment through both hydrophilic interaction liquid chromatography (HILIC) and weak anion exchange (WAX) principles. 26388377 10 1 theme liquid 1447:1452 arg1 chromatography 1454:1467 hydrophilic interaction liquid chromatography 1423:1467 hydrophilic interaction liquid chromatography (HILIC) 1423:1475 This corroborated that this stationary phase was exhibiting a mixed-mode enrichment through both hydrophilic interaction liquid chromatography (HILIC) and weak anion exchange (WAX) principles. 26388377 3 2 theme specific 527:534 arg1 heterogeneity 536:548 site specific heterogeneity 522:548 site specific heterogeneity 522:548 Studying these molecules at the glycopeptide level however, offers distinct advantages, namely the ability to characterize both the glycan and peptide fragments simultaneously, and moreover the ability to assign site specific heterogeneity. 26388377 5 3 theme enrichment 678:687 arg1 protocols 689:697 enrichment protocols 678:697 enrichment protocols prior to downstream MS analysis 678:729 For this reason, enrichment protocols prior to downstream MS analysis need to be developed. 26388377 1 4 theme human 161:165 arg1 physiology 167:176 human physiology 161:176 human physiology 161:176 Glycans are known to be involved in a variety of biological processes throughout human physiology. 26388377 10 5 theme interaction 1435:1445 arg1 HILIC 1470:1474 HILIC 1470:1474 HILIC 1470:1474 This corroborated that this stationary phase was exhibiting a mixed-mode enrichment through both hydrophilic interaction liquid chromatography (HILIC) and weak anion exchange (WAX) principles. 26388377 10 5 theme interaction 1435:1445 arg1 chromatography 1454:1467 hydrophilic interaction liquid chromatography 1423:1467 hydrophilic interaction liquid chromatography (HILIC) 1423:1475 This corroborated that this stationary phase was exhibiting a mixed-mode enrichment through both hydrophilic interaction liquid chromatography (HILIC) and weak anion exchange (WAX) principles. 26388377 7 6 theme glycopeptide 947:958 arg1 kit 971:973 a commercially available glycopeptide enrichment kit 922:973 a commercially available glycopeptide enrichment kit offered by EMD Millipore through the use of tandem mass tags (TMT) for relative quantification 922:1068 This protocol was compared to a commercially available glycopeptide enrichment kit offered by EMD Millipore through the use of tandem mass tags (TMT) for relative quantification. 26388377 10 7 theme hydrophilic 1423:1433 arg1 HILIC 1470:1474 HILIC 1470:1474 HILIC 1470:1474 This corroborated that this stationary phase was exhibiting a mixed-mode enrichment through both hydrophilic interaction liquid chromatography (HILIC) and weak anion exchange (WAX) principles. 26388377 10 7 theme hydrophilic 1423:1433 arg1 chromatography 1454:1467 hydrophilic interaction liquid chromatography 1423:1467 hydrophilic interaction liquid chromatography (HILIC) 1423:1475 This corroborated that this stationary phase was exhibiting a mixed-mode enrichment through both hydrophilic interaction liquid chromatography (HILIC) and weak anion exchange (WAX) principles. 26388377 9 8 theme reporter 1270:1277 arg1 ratios 1279:1284 TMT reporter ratios 1266:1284 TMT reporter ratios with respect to increasing sialylation 1266:1323 In addition, we observed a trend based on TMT reporter ratios with respect to increasing sialylation. 26388377 5 9 theme prior 699:703 arg1 protocols 689:697 enrichment protocols 678:697 enrichment protocols prior to downstream MS analysis 678:729 For this reason, enrichment protocols prior to downstream MS analysis need to be developed. 26388377 7 10 theme enrichment 960:969 arg1 kit 971:973 a commercially available glycopeptide enrichment kit 922:973 a commercially available glycopeptide enrichment kit offered by EMD Millipore through the use of tandem mass tags (TMT) for relative quantification 922:1068 This protocol was compared to a commercially available glycopeptide enrichment kit offered by EMD Millipore through the use of tandem mass tags (TMT) for relative quantification. 26388377 8 11 gly glycopeptides 1125:1137 arg2 glycopeptides 1125:1137 98 unique N-linked glycopeptides 1106:1137 98 unique N-linked glycopeptides 1106:1137 Using this approach, we identified 98 unique N-linked glycopeptides and observed, that CMCH was able to enrich more sialylation than the commercial kit. 26388377 4 12 gly glycopeptides 646:658 arg2 glycopeptides 646:658 glycopeptides 646:658 glycopeptides 646:658 In light of this, peptides often dominate the spectrum and hinder the ionization efficiency of glycopeptides. 26388377 2 13 theme glycans 301:307 arg1 characterization 281:296 quantitative and structural characterization 253:296 quantitative and structural characterization of glycans 253:307 Mass spectrometry has demonstrated itself as powerful analytical tool for quantitative and structural characterization of glycans. 26388377 3 14 theme distinct 377:384 arg1 advantages 386:395 distinct advantages 377:395 distinct advantages 377:395 Studying these molecules at the glycopeptide level however, offers distinct advantages, namely the ability to characterize both the glycan and peptide fragments simultaneously, and moreover the ability to assign site specific heterogeneity. 26388377 6 15 theme chitosan 809:816 arg1 use 788:790 the synthesis and use 770:790 use 788:790 Here, we discuss the synthesis and use of carboxymethyl chitosan (CMCH) to enrich glycopeptides from a 12 protein mixture for MS analysis. 26388377 6 15 theme chitosan 809:816 arg1 synthesis 774:782 the synthesis and use 770:790 synthesis 774:782 Here, we discuss the synthesis and use of carboxymethyl chitosan (CMCH) to enrich glycopeptides from a 12 protein mixture for MS analysis. 26388377 7 16 theme tags 1031:1034 arg1 use 1012:1014 the use 1008:1014 the use of tandem mass tags (TMT) for relative quantification 1008:1068 This protocol was compared to a commercially available glycopeptide enrichment kit offered by EMD Millipore through the use of tandem mass tags (TMT) for relative quantification. 26388377 6 17 theme MS 879:880 arg1 analysis 882:889 MS analysis 879:889 MS analysis 879:889 Here, we discuss the synthesis and use of carboxymethyl chitosan (CMCH) to enrich glycopeptides from a 12 protein mixture for MS analysis. 26388377 6 18 theme carboxymethyl 795:807 arg1 CMCH 819:822 CMCH 819:822 CMCH 819:822 Here, we discuss the synthesis and use of carboxymethyl chitosan (CMCH) to enrich glycopeptides from a 12 protein mixture for MS analysis. 26388377 6 18 theme carboxymethyl 795:807 arg1 chitosan 809:816 carboxymethyl chitosan 795:816 carboxymethyl chitosan (CMCH) 795:823 Here, we discuss the synthesis and use of carboxymethyl chitosan (CMCH) to enrich glycopeptides from a 12 protein mixture for MS analysis. 26388377 6 19 gly glycopeptides 835:847 arg1 mixture 867:873 a 12 protein mixture 854:873 a 12 protein mixture 854:873 Here, we discuss the synthesis and use of carboxymethyl chitosan (CMCH) to enrich glycopeptides from a 12 protein mixture for MS analysis. 26388377 6 19 gly glycopeptides 835:847 arg2 glycopeptides 835:847 glycopeptides 835:847 glycopeptides from a 12 protein mixture 835:873 Here, we discuss the synthesis and use of carboxymethyl chitosan (CMCH) to enrich glycopeptides from a 12 protein mixture for MS analysis. 26388377 10 20 dep chromatography 1454:1467 arg1 principles 1507:1516 principles 1507:1516 principles 1507:1516 This corroborated that this stationary phase was exhibiting a mixed-mode enrichment through both hydrophilic interaction liquid chromatography (HILIC) and weak anion exchange (WAX) principles. 26388377 10 21 theme mixed-mode 1388:1397 arg1 enrichment 1399:1408 a mixed-mode enrichment 1386:1408 a mixed-mode enrichment 1386:1408 This corroborated that this stationary phase was exhibiting a mixed-mode enrichment through both hydrophilic interaction liquid chromatography (HILIC) and weak anion exchange (WAX) principles. 26388377 3 22 theme peptide 453:459 arg1 fragments 461:469 peptide fragments 453:469 peptide fragments 453:469 Studying these molecules at the glycopeptide level however, offers distinct advantages, namely the ability to characterize both the glycan and peptide fragments simultaneously, and moreover the ability to assign site specific heterogeneity. 26388377 8 23 theme more 1182:1185 arg1 sialylation 1187:1197 more sialylation 1182:1197 more sialylation 1182:1197 Using this approach, we identified 98 unique N-linked glycopeptides and observed, that CMCH was able to enrich more sialylation than the commercial kit. 26388377 10 24 theme stationary 1354:1363 arg1 phase 1365:1369 this stationary phase 1349:1369 this stationary phase 1349:1369 This corroborated that this stationary phase was exhibiting a mixed-mode enrichment through both hydrophilic interaction liquid chromatography (HILIC) and weak anion exchange (WAX) principles. 26388377 6 25 from mixture 867:873 arg1 glycopeptides 835:847 glycopeptides 835:847 glycopeptides from a 12 protein mixture 835:873 Here, we discuss the synthesis and use of carboxymethyl chitosan (CMCH) to enrich glycopeptides from a 12 protein mixture for MS analysis. 26388377 10 26 theme anion 1486:1490 arg1 WAX 1502:1504 WAX 1502:1504 WAX 1502:1504 This corroborated that this stationary phase was exhibiting a mixed-mode enrichment through both hydrophilic interaction liquid chromatography (HILIC) and weak anion exchange (WAX) principles. 26388377 10 26 theme anion 1486:1490 arg1 exchange 1492:1499 weak anion exchange 1481:1499 weak anion exchange (WAX) 1481:1505 This corroborated that this stationary phase was exhibiting a mixed-mode enrichment through both hydrophilic interaction liquid chromatography (HILIC) and weak anion exchange (WAX) principles. 26388377 8 27 link N-linked 1116:1123 arg1 glycopeptides 1125:1137 98 unique N-linked glycopeptides 1106:1137 98 unique N-linked glycopeptides 1106:1137 Using this approach, we identified 98 unique N-linked glycopeptides and observed, that CMCH was able to enrich more sialylation than the commercial kit. 26388377 0 28 theme chitosan 42:49 arg1 evaluation 14:23 evaluation 14:23 evaluation 14:23 Synthesis and evaluation of carboxymethyl chitosan for glycopeptide enrichment. 26388377 0 28 theme chitosan 42:49 arg1 Synthesis 0:8 Synthesis 0:8 Synthesis 0:8 Synthesis and evaluation of carboxymethyl chitosan for glycopeptide enrichment. 26388377 10 29 theme weak 1481:1484 arg1 WAX 1502:1504 WAX 1502:1504 WAX 1502:1504 This corroborated that this stationary phase was exhibiting a mixed-mode enrichment through both hydrophilic interaction liquid chromatography (HILIC) and weak anion exchange (WAX) principles. 26388377 10 29 theme weak 1481:1484 arg1 exchange 1492:1499 weak anion exchange 1481:1499 weak anion exchange (WAX) 1481:1505 This corroborated that this stationary phase was exhibiting a mixed-mode enrichment through both hydrophilic interaction liquid chromatography (HILIC) and weak anion exchange (WAX) principles. 26388377 2 30 theme Mass 179:182 arg1 spectrometry 184:195 Mass spectrometry 179:195 Mass spectrometry 179:195 Mass spectrometry has demonstrated itself as powerful analytical tool for quantitative and structural characterization of glycans. 26388377 0 31 theme carboxymethyl 28:40 arg1 chitosan 42:49 carboxymethyl chitosan 28:49 carboxymethyl chitosan 28:49 Synthesis and evaluation of carboxymethyl chitosan for glycopeptide enrichment. 26388377 7 32 theme relative 1046:1053 arg1 quantification 1055:1068 relative quantification 1046:1068 relative quantification 1046:1068 This protocol was compared to a commercially available glycopeptide enrichment kit offered by EMD Millipore through the use of tandem mass tags (TMT) for relative quantification. 26388377 6 33 theme protein 859:865 arg1 mixture 867:873 a 12 protein mixture 854:873 a 12 protein mixture 854:873 Here, we discuss the synthesis and use of carboxymethyl chitosan (CMCH) to enrich glycopeptides from a 12 protein mixture for MS analysis. 26388377 7 34 theme tandem 1019:1024 arg1 TMT 1037:1039 TMT 1037:1039 TMT 1037:1039 This protocol was compared to a commercially available glycopeptide enrichment kit offered by EMD Millipore through the use of tandem mass tags (TMT) for relative quantification. 26388377 7 34 theme tandem 1019:1024 arg1 tags 1031:1034 tandem mass tags 1019:1034 tandem mass tags (TMT) for relative quantification 1019:1068 This protocol was compared to a commercially available glycopeptide enrichment kit offered by EMD Millipore through the use of tandem mass tags (TMT) for relative quantification. 26388377 0 35 theme glycopeptide 55:66 arg1 enrichment 68:77 glycopeptide enrichment 55:77 glycopeptide enrichment 55:77 Synthesis and evaluation of carboxymethyl chitosan for glycopeptide enrichment. 26388377 8 36 theme N-linked 1116:1123 arg1 glycopeptides 1125:1137 98 unique N-linked glycopeptides 1106:1137 98 unique N-linked glycopeptides 1106:1137 Using this approach, we identified 98 unique N-linked glycopeptides and observed, that CMCH was able to enrich more sialylation than the commercial kit. 26388377 2 37 theme analytical 233:242 arg1 tool 244:247 powerful analytical tool 224:247 powerful analytical tool for quantitative and structural characterization of glycans 224:307 Mass spectrometry has demonstrated itself as powerful analytical tool for quantitative and structural characterization of glycans. 26388377 7 38 theme mass 1026:1029 arg1 TMT 1037:1039 TMT 1037:1039 TMT 1037:1039 This protocol was compared to a commercially available glycopeptide enrichment kit offered by EMD Millipore through the use of tandem mass tags (TMT) for relative quantification. 26388377 7 38 theme mass 1026:1029 arg1 tags 1031:1034 tandem mass tags 1019:1034 tandem mass tags (TMT) for relative quantification 1019:1068 This protocol was compared to a commercially available glycopeptide enrichment kit offered by EMD Millipore through the use of tandem mass tags (TMT) for relative quantification. 26388377 9 39 theme TMT 1266:1268 arg1 ratios 1279:1284 TMT reporter ratios 1266:1284 TMT reporter ratios with respect to increasing sialylation 1266:1323 In addition, we observed a trend based on TMT reporter ratios with respect to increasing sialylation. 26388377 5 40 theme downstream 708:717 arg1 analysis 722:729 downstream MS analysis 708:729 downstream MS analysis 708:729 For this reason, enrichment protocols prior to downstream MS analysis need to be developed. 26388377 2 41 theme powerful 224:231 arg1 tool 244:247 powerful analytical tool 224:247 powerful analytical tool for quantitative and structural characterization of glycans 224:307 Mass spectrometry has demonstrated itself as powerful analytical tool for quantitative and structural characterization of glycans. 26388377 4 42 theme this 563:566 arg1 light 554:558 light 554:558 light of this 554:566 In light of this, peptides often dominate the spectrum and hinder the ionization efficiency of glycopeptides. 26388377 5 43 theme MS 719:720 arg1 analysis 722:729 downstream MS analysis 708:729 downstream MS analysis 708:729 For this reason, enrichment protocols prior to downstream MS analysis need to be developed. 26388377 7 44 theme available 937:945 arg1 kit 971:973 a commercially available glycopeptide enrichment kit 922:973 a commercially available glycopeptide enrichment kit offered by EMD Millipore through the use of tandem mass tags (TMT) for relative quantification 922:1068 This protocol was compared to a commercially available glycopeptide enrichment kit offered by EMD Millipore through the use of tandem mass tags (TMT) for relative quantification. 26388377 0 45 gly glycopeptide 55:66 arg2 glycopeptide 55:66 glycopeptide enrichment 55:77 glycopeptide enrichment 55:77 Synthesis and evaluation of carboxymethyl chitosan for glycopeptide enrichment. 26388377 7 46 gly glycopeptide 947:958 arg2 glycopeptide 947:958 a commercially available glycopeptide enrichment kit 922:973 a commercially available glycopeptide enrichment kit offered by EMD Millipore through the use of tandem mass tags (TMT) for relative quantification 922:1068 This protocol was compared to a commercially available glycopeptide enrichment kit offered by EMD Millipore through the use of tandem mass tags (TMT) for relative quantification. 26388377 3 47 gly glycopeptide 342:353 arg2 glycopeptide 342:353 the glycopeptide level 338:359 the glycopeptide level 338:359 Studying these molecules at the glycopeptide level however, offers distinct advantages, namely the ability to characterize both the glycan and peptide fragments simultaneously, and moreover the ability to assign site specific heterogeneity. 26388377 2 48 theme structural 270:279 arg1 characterization 281:296 quantitative and structural characterization 253:296 quantitative and structural characterization of glycans 253:307 Mass spectrometry has demonstrated itself as powerful analytical tool for quantitative and structural characterization of glycans. 26388377 8 49 theme unique 1109:1114 arg1 glycopeptides 1125:1137 98 unique N-linked glycopeptides 1106:1137 98 unique N-linked glycopeptides 1106:1137 Using this approach, we identified 98 unique N-linked glycopeptides and observed, that CMCH was able to enrich more sialylation than the commercial kit. 26388377 4 50 theme ionization 621:630 arg1 efficiency 632:641 the ionization efficiency 617:641 the ionization efficiency of glycopeptides 617:658 In light of this, peptides often dominate the spectrum and hinder the ionization efficiency of glycopeptides. 26388377 1 51 theme biological 129:138 arg1 processes 140:148 biological processes 129:148 biological processes throughout human physiology 129:176 Glycans are known to be involved in a variety of biological processes throughout human physiology. 26388377 4 52 theme glycopeptides 646:658 arg1 efficiency 632:641 the ionization efficiency 617:641 the ionization efficiency of glycopeptides 617:658 In light of this, peptides often dominate the spectrum and hinder the ionization efficiency of glycopeptides. 26388377 8 53 theme commercial 1208:1217 arg1 kit 1219:1221 the commercial kit 1204:1221 the commercial kit 1204:1221 Using this approach, we identified 98 unique N-linked glycopeptides and observed, that CMCH was able to enrich more sialylation than the commercial kit. 26388377 2 54 theme quantitative 253:264 arg1 characterization 281:296 quantitative and structural characterization 253:296 quantitative and structural characterization of glycans 253:307 Mass spectrometry has demonstrated itself as powerful analytical tool for quantitative and structural characterization of glycans. 26388377 1 55 theme processes 140:148 arg1 variety 118:124 a variety 116:124 a variety of biological processes throughout human physiology 116:176 Glycans are known to be involved in a variety of biological processes throughout human physiology. 26388377 1 55 theme processes 140:148 arg1 processes 140:148 biological processes 129:148 biological processes throughout human physiology 129:176 Glycans are known to be involved in a variety of biological processes throughout human physiology. 26241493 3 0 dep lines 725:729 arg1 MCF10A 753:758 MCF10A 753:758 MCF10A 753:758 A route for the biosynthesis of this new bioactive macrocycle is proposed and the cytotoxicity of the compound was evaluated against two ATCC cell lines - one normal-derived (MCF10A) and one cancer-derived cell line (MCF7) - using the MTT assay. 26241493 3 0 dep lines 725:729 arg1 normal-derived 737:750 normal-derived 737:750 normal-derived 737:750 A route for the biosynthesis of this new bioactive macrocycle is proposed and the cytotoxicity of the compound was evaluated against two ATCC cell lines - one normal-derived (MCF10A) and one cancer-derived cell line (MCF7) - using the MTT assay. 26241493 3 0 dep lines 725:729 arg1 MCF7 795:798 MCF7 795:798 MCF7 795:798 A route for the biosynthesis of this new bioactive macrocycle is proposed and the cytotoxicity of the compound was evaluated against two ATCC cell lines - one normal-derived (MCF10A) and one cancer-derived cell line (MCF7) - using the MTT assay. 26241493 3 0 dep lines 725:729 arg1 using 803:807 using 803:807 using the MTT assay 803:821 A route for the biosynthesis of this new bioactive macrocycle is proposed and the cytotoxicity of the compound was evaluated against two ATCC cell lines - one normal-derived (MCF10A) and one cancer-derived cell line (MCF7) - using the MTT assay. 26241493 3 0 dep lines 725:729 arg1 line 789:792 one cancer-derived cell line 765:792 one cancer-derived cell line (MCF7) 765:799 A route for the biosynthesis of this new bioactive macrocycle is proposed and the cytotoxicity of the compound was evaluated against two ATCC cell lines - one normal-derived (MCF10A) and one cancer-derived cell line (MCF7) - using the MTT assay. 26241493 1 1 dep isolation 84:92 arg1 The 80:82 The 80:82 The 80:82 The isolation and structural elucidation of a macrocyclic alkaloid, characterized by the presence of a 13-membered macrolactam ring containing a spermidine unit N-linked to a benzoyl group is hereby reported. 26241493 2 2 theme NMR 446:448 arg1 spectroscopy 450:461 (13)C NMR spectroscopy 440:461 (13)C NMR spectroscopy (including bidimensional analysis) 440:496 The structure of this previously unknown spermidine alkaloid isolated from Gymnosporia arenicola (Celastraceae) leaves has been elucidated by (1)H and (13)C NMR spectroscopy (including bidimensional analysis) and further characterized by high-resolution mass spectrometry and polarimetry. 26241493 1 3 theme benzoyl 255:261 arg1 group 263:267 a benzoyl group 253:267 a benzoyl group 253:267 The isolation and structural elucidation of a macrocyclic alkaloid, characterized by the presence of a 13-membered macrolactam ring containing a spermidine unit N-linked to a benzoyl group is hereby reported. 26241493 2 4 theme unknown 322:328 arg1 alkaloid 341:348 this previously unknown spermidine alkaloid 306:348 this previously unknown spermidine alkaloid isolated from Gymnosporia arenicola (Celastraceae) 306:399 The structure of this previously unknown spermidine alkaloid isolated from Gymnosporia arenicola (Celastraceae) leaves has been elucidated by (1)H and (13)C NMR spectroscopy (including bidimensional analysis) and further characterized by high-resolution mass spectrometry and polarimetry. 26241493 2 5 attach isolated 350:357 arg1 Celastraceae 387:398 Celastraceae 387:398 Celastraceae 387:398 The structure of this previously unknown spermidine alkaloid isolated from Gymnosporia arenicola (Celastraceae) leaves has been elucidated by (1)H and (13)C NMR spectroscopy (including bidimensional analysis) and further characterized by high-resolution mass spectrometry and polarimetry. 26241493 2 5 attach isolated 350:357 arg1 arenicola 376:384 arenicola 376:384 arenicola 376:384 The structure of this previously unknown spermidine alkaloid isolated from Gymnosporia arenicola (Celastraceae) leaves has been elucidated by (1)H and (13)C NMR spectroscopy (including bidimensional analysis) and further characterized by high-resolution mass spectrometry and polarimetry. 26241493 2 5 attach isolated 350:357 arg2 alkaloid 341:348 this previously unknown spermidine alkaloid 306:348 this previously unknown spermidine alkaloid isolated from Gymnosporia arenicola (Celastraceae) 306:399 The structure of this previously unknown spermidine alkaloid isolated from Gymnosporia arenicola (Celastraceae) leaves has been elucidated by (1)H and (13)C NMR spectroscopy (including bidimensional analysis) and further characterized by high-resolution mass spectrometry and polarimetry. 26241493 2 6 theme bidimensional 474:486 arg1 analysis 488:495 bidimensional analysis 474:495 bidimensional analysis 474:495 The structure of this previously unknown spermidine alkaloid isolated from Gymnosporia arenicola (Celastraceae) leaves has been elucidated by (1)H and (13)C NMR spectroscopy (including bidimensional analysis) and further characterized by high-resolution mass spectrometry and polarimetry. 26241493 1 7 link N-linked 241:248 arg1 unit 236:239 a spermidine unit 223:239 a spermidine unit N-linked to a benzoyl group 223:267 The isolation and structural elucidation of a macrocyclic alkaloid, characterized by the presence of a 13-membered macrolactam ring containing a spermidine unit N-linked to a benzoyl group is hereby reported. 26241493 3 8 theme cell 784:787 arg1 MCF7 795:798 MCF7 795:798 MCF7 795:798 A route for the biosynthesis of this new bioactive macrocycle is proposed and the cytotoxicity of the compound was evaluated against two ATCC cell lines - one normal-derived (MCF10A) and one cancer-derived cell line (MCF7) - using the MTT assay. 26241493 3 8 theme cell 784:787 arg1 line 789:792 one cancer-derived cell line 765:792 one cancer-derived cell line (MCF7) 765:799 A route for the biosynthesis of this new bioactive macrocycle is proposed and the cytotoxicity of the compound was evaluated against two ATCC cell lines - one normal-derived (MCF10A) and one cancer-derived cell line (MCF7) - using the MTT assay. 26241493 0 9 theme new 2:4 arg1 alkaloid 29:36 A new spermidine macrocyclic alkaloid 0:36 A new spermidine macrocyclic alkaloid 0:36 A new spermidine macrocyclic alkaloid isolated from Gymnosporia arenicola leaf. 26241493 3 10 theme ATCC 715:718 arg1 lines 725:729 two ATCC cell lines 711:729 two ATCC cell lines - one normal-derived (MCF10A) and one cancer-derived cell line (MCF7) - using the MTT assay 711:821 A route for the biosynthesis of this new bioactive macrocycle is proposed and the cytotoxicity of the compound was evaluated against two ATCC cell lines - one normal-derived (MCF10A) and one cancer-derived cell line (MCF7) - using the MTT assay. 26241493 2 11 dep H 434:434 arg1 1 432:432 1 432:432 1 432:432 The structure of this previously unknown spermidine alkaloid isolated from Gymnosporia arenicola (Celastraceae) leaves has been elucidated by (1)H and (13)C NMR spectroscopy (including bidimensional analysis) and further characterized by high-resolution mass spectrometry and polarimetry. 26241493 3 12 link cancer-derived 769:782 arg1 MCF7 795:798 MCF7 795:798 MCF7 795:798 A route for the biosynthesis of this new bioactive macrocycle is proposed and the cytotoxicity of the compound was evaluated against two ATCC cell lines - one normal-derived (MCF10A) and one cancer-derived cell line (MCF7) - using the MTT assay. 26241493 3 12 link cancer-derived 769:782 arg1 line 789:792 one cancer-derived cell line 765:792 one cancer-derived cell line (MCF7) 765:799 A route for the biosynthesis of this new bioactive macrocycle is proposed and the cytotoxicity of the compound was evaluated against two ATCC cell lines - one normal-derived (MCF10A) and one cancer-derived cell line (MCF7) - using the MTT assay. 26241493 1 13 theme 13-membered 183:193 arg1 ring 207:210 a 13-membered macrolactam ring 181:210 a 13-membered macrolactam ring 181:210 The isolation and structural elucidation of a macrocyclic alkaloid, characterized by the presence of a 13-membered macrolactam ring containing a spermidine unit N-linked to a benzoyl group is hereby reported. 26241493 0 14 theme macrocyclic 17:27 arg1 alkaloid 29:36 A new spermidine macrocyclic alkaloid 0:36 A new spermidine macrocyclic alkaloid 0:36 A new spermidine macrocyclic alkaloid isolated from Gymnosporia arenicola leaf. 26241493 2 15 theme high-resolution 527:541 arg1 spectrometry 548:559 high-resolution mass spectrometry 527:559 high-resolution mass spectrometry 527:559 The structure of this previously unknown spermidine alkaloid isolated from Gymnosporia arenicola (Celastraceae) leaves has been elucidated by (1)H and (13)C NMR spectroscopy (including bidimensional analysis) and further characterized by high-resolution mass spectrometry and polarimetry. 26241493 1 16 theme structural 98:107 arg1 elucidation 109:119 structural elucidation 98:119 structural elucidation of a macrocyclic alkaloid, characterized by the presence of a 13-membered macrolactam ring 98:210 The isolation and structural elucidation of a macrocyclic alkaloid, characterized by the presence of a 13-membered macrolactam ring containing a spermidine unit N-linked to a benzoyl group is hereby reported. 26241493 1 17 theme macrolactam 195:205 arg1 ring 207:210 a 13-membered macrolactam ring 181:210 a 13-membered macrolactam ring 181:210 The isolation and structural elucidation of a macrocyclic alkaloid, characterized by the presence of a 13-membered macrolactam ring containing a spermidine unit N-linked to a benzoyl group is hereby reported. 26241493 0 18 theme spermidine 6:15 arg1 alkaloid 29:36 A new spermidine macrocyclic alkaloid 0:36 A new spermidine macrocyclic alkaloid 0:36 A new spermidine macrocyclic alkaloid isolated from Gymnosporia arenicola leaf. 26241493 3 19 theme cell 720:723 arg1 lines 725:729 two ATCC cell lines 711:729 two ATCC cell lines - one normal-derived (MCF10A) and one cancer-derived cell line (MCF7) - using the MTT assay 711:821 A route for the biosynthesis of this new bioactive macrocycle is proposed and the cytotoxicity of the compound was evaluated against two ATCC cell lines - one normal-derived (MCF10A) and one cancer-derived cell line (MCF7) - using the MTT assay. 26241493 3 20 theme macrocycle 629:638 arg1 biosynthesis 594:605 the biosynthesis 590:605 the biosynthesis of this new bioactive macrocycle 590:638 A route for the biosynthesis of this new bioactive macrocycle is proposed and the cytotoxicity of the compound was evaluated against two ATCC cell lines - one normal-derived (MCF10A) and one cancer-derived cell line (MCF7) - using the MTT assay. 26241493 1 21 theme ring 207:210 arg1 presence 169:176 the presence 165:176 the presence of a 13-membered macrolactam ring 165:210 The isolation and structural elucidation of a macrocyclic alkaloid, characterized by the presence of a 13-membered macrolactam ring containing a spermidine unit N-linked to a benzoyl group is hereby reported. 26241493 2 22 theme C 444:444 arg1 spectroscopy 450:461 (13)C NMR spectroscopy 440:461 (13)C NMR spectroscopy (including bidimensional analysis) 440:496 The structure of this previously unknown spermidine alkaloid isolated from Gymnosporia arenicola (Celastraceae) leaves has been elucidated by (1)H and (13)C NMR spectroscopy (including bidimensional analysis) and further characterized by high-resolution mass spectrometry and polarimetry. 26241493 4 23 theme cell 879:882 arg1 lines 884:888 both cell lines 874:888 both cell lines 874:888 The alkaloid revealed to be non-cytotoxic against both cell lines. 26241493 3 24 theme new 615:617 arg1 macrocycle 629:638 this new bioactive macrocycle 610:638 this new bioactive macrocycle 610:638 A route for the biosynthesis of this new bioactive macrocycle is proposed and the cytotoxicity of the compound was evaluated against two ATCC cell lines - one normal-derived (MCF10A) and one cancer-derived cell line (MCF7) - using the MTT assay. 26241493 0 25 theme Gymnosporia 52:62 arg1 leaf 74:77 Gymnosporia arenicola leaf 52:77 Gymnosporia arenicola leaf 52:77 A new spermidine macrocyclic alkaloid isolated from Gymnosporia arenicola leaf. 26241493 2 26 dep spectroscopy 450:461 arg1 including 464:472 including 464:472 including bidimensional analysis 464:495 The structure of this previously unknown spermidine alkaloid isolated from Gymnosporia arenicola (Celastraceae) leaves has been elucidated by (1)H and (13)C NMR spectroscopy (including bidimensional analysis) and further characterized by high-resolution mass spectrometry and polarimetry. 26241493 3 27 theme bioactive 619:627 arg1 macrocycle 629:638 this new bioactive macrocycle 610:638 this new bioactive macrocycle 610:638 A route for the biosynthesis of this new bioactive macrocycle is proposed and the cytotoxicity of the compound was evaluated against two ATCC cell lines - one normal-derived (MCF10A) and one cancer-derived cell line (MCF7) - using the MTT assay. 26241493 5 28 theme IC50 895:898 arg1 values 900:905 The IC50 values 891:905 The IC50 values from the cells 891:920 The IC50 values from the cells were also determined. 26241493 2 29 theme alkaloid 341:348 arg1 structure 293:301 The structure 289:301 The structure of this previously unknown spermidine alkaloid isolated from Gymnosporia arenicola (Celastraceae) 289:399 The structure of this previously unknown spermidine alkaloid isolated from Gymnosporia arenicola (Celastraceae) leaves has been elucidated by (1)H and (13)C NMR spectroscopy (including bidimensional analysis) and further characterized by high-resolution mass spectrometry and polarimetry. 26241493 1 30 contain containing 212:221 arg2 unit 236:239 a spermidine unit 223:239 a spermidine unit N-linked to a benzoyl group 223:267 The isolation and structural elucidation of a macrocyclic alkaloid, characterized by the presence of a 13-membered macrolactam ring containing a spermidine unit N-linked to a benzoyl group is hereby reported. 26241493 1 30 contain containing 212:221 arg1 isolation 84:92 isolation 84:92 isolation 84:92 The isolation and structural elucidation of a macrocyclic alkaloid, characterized by the presence of a 13-membered macrolactam ring containing a spermidine unit N-linked to a benzoyl group is hereby reported. 26241493 1 31 theme macrocyclic 126:136 arg1 alkaloid 138:145 a macrocyclic alkaloid 124:145 a macrocyclic alkaloid 124:145 The isolation and structural elucidation of a macrocyclic alkaloid, characterized by the presence of a 13-membered macrolactam ring containing a spermidine unit N-linked to a benzoyl group is hereby reported. 26241493 3 32 theme MTT 813:815 arg1 assay 817:821 the MTT assay 809:821 the MTT assay 809:821 A route for the biosynthesis of this new bioactive macrocycle is proposed and the cytotoxicity of the compound was evaluated against two ATCC cell lines - one normal-derived (MCF10A) and one cancer-derived cell line (MCF7) - using the MTT assay. 26241493 1 33 theme spermidine 225:234 arg1 unit 236:239 a spermidine unit 223:239 a spermidine unit N-linked to a benzoyl group 223:267 The isolation and structural elucidation of a macrocyclic alkaloid, characterized by the presence of a 13-membered macrolactam ring containing a spermidine unit N-linked to a benzoyl group is hereby reported. 26241493 2 34 theme mass 543:546 arg1 spectrometry 548:559 high-resolution mass spectrometry 527:559 high-resolution mass spectrometry 527:559 The structure of this previously unknown spermidine alkaloid isolated from Gymnosporia arenicola (Celastraceae) leaves has been elucidated by (1)H and (13)C NMR spectroscopy (including bidimensional analysis) and further characterized by high-resolution mass spectrometry and polarimetry. 26241493 1 35 theme alkaloid 138:145 arg1 isolation 84:92 isolation 84:92 isolation 84:92 The isolation and structural elucidation of a macrocyclic alkaloid, characterized by the presence of a 13-membered macrolactam ring containing a spermidine unit N-linked to a benzoyl group is hereby reported. 26241493 1 35 theme alkaloid 138:145 arg1 elucidation 109:119 structural elucidation 98:119 structural elucidation of a macrocyclic alkaloid, characterized by the presence of a 13-membered macrolactam ring 98:210 The isolation and structural elucidation of a macrocyclic alkaloid, characterized by the presence of a 13-membered macrolactam ring containing a spermidine unit N-linked to a benzoyl group is hereby reported. 26241493 2 36 theme spermidine 330:339 arg1 alkaloid 341:348 this previously unknown spermidine alkaloid 306:348 this previously unknown spermidine alkaloid isolated from Gymnosporia arenicola (Celastraceae) 306:399 The structure of this previously unknown spermidine alkaloid isolated from Gymnosporia arenicola (Celastraceae) leaves has been elucidated by (1)H and (13)C NMR spectroscopy (including bidimensional analysis) and further characterized by high-resolution mass spectrometry and polarimetry. 26241493 1 37 theme N-linked 241:248 arg1 unit 236:239 a spermidine unit 223:239 a spermidine unit N-linked to a benzoyl group 223:267 The isolation and structural elucidation of a macrocyclic alkaloid, characterized by the presence of a 13-membered macrolactam ring containing a spermidine unit N-linked to a benzoyl group is hereby reported. 26241493 0 38 theme arenicola 64:72 arg1 leaf 74:77 Gymnosporia arenicola leaf 52:77 Gymnosporia arenicola leaf 52:77 A new spermidine macrocyclic alkaloid isolated from Gymnosporia arenicola leaf. 26241493 3 39 theme compound 680:687 arg1 cytotoxicity 660:671 the cytotoxicity 656:671 the cytotoxicity of the compound 656:687 A route for the biosynthesis of this new bioactive macrocycle is proposed and the cytotoxicity of the compound was evaluated against two ATCC cell lines - one normal-derived (MCF10A) and one cancer-derived cell line (MCF7) - using the MTT assay. 26241493 2 40 dep leaves 401:406 arg1 elucidated 417:426 elucidated 417:426 elucidated by (1)H and (13)C NMR spectroscopy (including bidimensional analysis) 417:496 The structure of this previously unknown spermidine alkaloid isolated from Gymnosporia arenicola (Celastraceae) leaves has been elucidated by (1)H and (13)C NMR spectroscopy (including bidimensional analysis) and further characterized by high-resolution mass spectrometry and polarimetry. 26241493 2 40 dep leaves 401:406 arg1 characterized 510:522 characterized 510:522 further characterized by high-resolution mass spectrometry and polarimetry 502:575 The structure of this previously unknown spermidine alkaloid isolated from Gymnosporia arenicola (Celastraceae) leaves has been elucidated by (1)H and (13)C NMR spectroscopy (including bidimensional analysis) and further characterized by high-resolution mass spectrometry and polarimetry. 26241493 3 41 theme cancer-derived 769:782 arg1 MCF7 795:798 MCF7 795:798 MCF7 795:798 A route for the biosynthesis of this new bioactive macrocycle is proposed and the cytotoxicity of the compound was evaluated against two ATCC cell lines - one normal-derived (MCF10A) and one cancer-derived cell line (MCF7) - using the MTT assay. 26241493 3 41 theme cancer-derived 769:782 arg1 line 789:792 one cancer-derived cell line 765:792 one cancer-derived cell line (MCF7) 765:799 A route for the biosynthesis of this new bioactive macrocycle is proposed and the cytotoxicity of the compound was evaluated against two ATCC cell lines - one normal-derived (MCF10A) and one cancer-derived cell line (MCF7) - using the MTT assay. 26241493 5 42 from cells 916:920 arg1 values 900:905 The IC50 values 891:905 The IC50 values from the cells 891:920 The IC50 values from the cells were also determined. 28071783 5 0 theme silver 869:874 arg1 nanoparticles 876:888 silver nanoparticles 869:888 silver nanoparticles 869:888 GO/Fe3O4/PEI/Ag nanocomposites offered excellent enrichment ability, which was attributed to the synergistic effect of polyethylenimine and silver nanoparticles. 28071783 8 1 gly glycopeptides 1268:1280 arg2 glycopeptides 1268:1280 136 N-linked glycopeptides 1255:1280 136 N-linked glycopeptides 1255:1280 Using these nanocomposites, 91 different glycoproteins and 136 N-linked glycopeptides were identified from among 20 μg tryptic human serum proteins and this demonstrated the superior performance of the nanocomposites for glycopeptides enrichment. 28071783 2 2 theme silver 382:387 arg1 nanocomposites 441:454 silver nanoparticle-functionalized magnetic graphene oxide nanocomposites 382:454 silver nanoparticle-functionalized magnetic graphene oxide nanocomposites (GO/Fe3O4/PEI/Ag) 382:472 In this study, silver nanoparticle-functionalized magnetic graphene oxide nanocomposites (GO/Fe3O4/PEI/Ag) were synthesized. 28071783 2 2 theme silver 382:387 arg1 GO/Fe3O4/PEI/Ag 457:471 GO/Fe3O4/PEI/Ag 457:471 GO/Fe3O4/PEI/Ag 457:471 In this study, silver nanoparticle-functionalized magnetic graphene oxide nanocomposites (GO/Fe3O4/PEI/Ag) were synthesized. 28071783 5 3 theme nanoparticles 876:888 arg1 effect 838:843 the synergistic effect 822:843 the synergistic effect of polyethylenimine and silver nanoparticles 822:888 GO/Fe3O4/PEI/Ag nanocomposites offered excellent enrichment ability, which was attributed to the synergistic effect of polyethylenimine and silver nanoparticles. 28071783 5 4 theme GO/Fe3O4/PEI/Ag 729:743 arg1 nanocomposites 745:758 GO/Fe3O4/PEI/Ag nanocomposites 729:758 GO/Fe3O4/PEI/Ag nanocomposites 729:758 GO/Fe3O4/PEI/Ag nanocomposites offered excellent enrichment ability, which was attributed to the synergistic effect of polyethylenimine and silver nanoparticles. 28071783 1 5 theme mass 206:209 arg1 MS 225:226 MS 225:226 MS 225:226 Although selective enrichment of glycopeptides from complex biological samples is indispensable for mass spectrometry (MS)-based glycoproteomics, it still remains a great challenge due to the low abundance of glycoproteins and suppression of non-glycopeptides. 28071783 1 5 theme mass 206:209 arg1 spectrometry 211:222 mass spectrometry 206:222 mass spectrometry (MS)-based glycoproteomics 206:249 Although selective enrichment of glycopeptides from complex biological samples is indispensable for mass spectrometry (MS)-based glycoproteomics, it still remains a great challenge due to the low abundance of glycoproteins and suppression of non-glycopeptides. 28071783 1 6 theme due 287:289 arg1 challenge 277:285 a great challenge 269:285 a great challenge due to the low abundance of glycoproteins and suppression of non-glycopeptides 269:364 Although selective enrichment of glycopeptides from complex biological samples is indispensable for mass spectrometry (MS)-based glycoproteomics, it still remains a great challenge due to the low abundance of glycoproteins and suppression of non-glycopeptides. 28071783 7 7 theme low 1113:1115 arg1 limit 1127:1131 low detection limit 1113:1131 low detection limit (25 fmol) 1113:1141 The nanocomposites displayed advantages including rapid adsorption (1 min), low detection limit (25 fmol), repeatability (6 times), and high recovery (77.8%). 28071783 7 7 theme low 1113:1115 arg1 fmol 1137:1140 25 fmol 1134:1140 25 fmol 1134:1140 The nanocomposites displayed advantages including rapid adsorption (1 min), low detection limit (25 fmol), repeatability (6 times), and high recovery (77.8%). 28071783 3 8 theme reducing 606:613 arg1 agent 631:635 a reducing and stabilizing agent 604:635 a reducing and stabilizing agent 604:635 Silver nanoparticles were generated in situ on the surface of magnetic graphene oxide using polyethylenimine as a reducing and stabilizing agent. 28071783 3 8 theme reducing 606:613 arg1 polyethylenimine 584:599 polyethylenimine 584:599 polyethylenimine 584:599 Silver nanoparticles were generated in situ on the surface of magnetic graphene oxide using polyethylenimine as a reducing and stabilizing agent. 28071783 5 9 theme synergistic 826:836 arg1 effect 838:843 the synergistic effect 822:843 the synergistic effect of polyethylenimine and silver nanoparticles 822:888 GO/Fe3O4/PEI/Ag nanocomposites offered excellent enrichment ability, which was attributed to the synergistic effect of polyethylenimine and silver nanoparticles. 28071783 8 10 gly glycopeptides 1417:1429 arg2 glycopeptides 1417:1429 glycopeptides enrichment 1417:1440 glycopeptides enrichment 1417:1440 Using these nanocomposites, 91 different glycoproteins and 136 N-linked glycopeptides were identified from among 20 μg tryptic human serum proteins and this demonstrated the superior performance of the nanocomposites for glycopeptides enrichment. 28071783 3 11 theme graphene 563:570 arg1 oxide 572:576 magnetic graphene oxide 554:576 magnetic graphene oxide using polyethylenimine as a reducing and stabilizing agent 554:635 Silver nanoparticles were generated in situ on the surface of magnetic graphene oxide using polyethylenimine as a reducing and stabilizing agent. 28071783 6 12 gly non-glycopeptides 966:982 arg2 non-glycopeptides 966:982 non-glycopeptides 966:982 non-glycopeptides 966:982 The nanocomposites showed superior specificity for glycopeptides even when non-glycopeptides were 100 times more concentrated than glycopeptides. 28071783 8 13 theme nanocomposites 1398:1411 arg1 performance 1379:1389 the superior performance 1366:1389 the superior performance of the nanocomposites for glycopeptides enrichment 1366:1440 Using these nanocomposites, 91 different glycoproteins and 136 N-linked glycopeptides were identified from among 20 μg tryptic human serum proteins and this demonstrated the superior performance of the nanocomposites for glycopeptides enrichment. 28071783 1 14 gly glycopeptides 139:151 arg2 glycopeptides 139:151 glycopeptides 139:151 glycopeptides 139:151 Although selective enrichment of glycopeptides from complex biological samples is indispensable for mass spectrometry (MS)-based glycoproteomics, it still remains a great challenge due to the low abundance of glycoproteins and suppression of non-glycopeptides. 28071783 6 15 theme superior 917:924 arg1 specificity 926:936 superior specificity 917:936 superior specificity for glycopeptides 917:954 The nanocomposites showed superior specificity for glycopeptides even when non-glycopeptides were 100 times more concentrated than glycopeptides. 28071783 1 16 theme spectrometry 211:222 arg1 glycoproteomics 235:249 mass spectrometry (MS)-based glycoproteomics 206:249 mass spectrometry (MS)-based glycoproteomics 206:249 Although selective enrichment of glycopeptides from complex biological samples is indispensable for mass spectrometry (MS)-based glycoproteomics, it still remains a great challenge due to the low abundance of glycoproteins and suppression of non-glycopeptides. 28071783 8 17 theme tryptic 1315:1321 arg1 serum 1329:1333 20 μg tryptic human serum 1309:1333 20 μg tryptic human serum proteins 1309:1342 Using these nanocomposites, 91 different glycoproteins and 136 N-linked glycopeptides were identified from among 20 μg tryptic human serum proteins and this demonstrated the superior performance of the nanocomposites for glycopeptides enrichment. 28071783 8 18 theme serum 1329:1333 arg1 proteins 1335:1342 20 μg tryptic human serum proteins 1309:1342 20 μg tryptic human serum proteins 1309:1342 Using these nanocomposites, 91 different glycoproteins and 136 N-linked glycopeptides were identified from among 20 μg tryptic human serum proteins and this demonstrated the superior performance of the nanocomposites for glycopeptides enrichment. 28071783 8 19 theme different 1227:1235 arg1 glycoproteins 1237:1249 91 different glycoproteins 1224:1249 91 different glycoproteins 1224:1249 Using these nanocomposites, 91 different glycoproteins and 136 N-linked glycopeptides were identified from among 20 μg tryptic human serum proteins and this demonstrated the superior performance of the nanocomposites for glycopeptides enrichment. 28071783 1 20 from samples 177:183 arg1 enrichment 125:134 selective enrichment 115:134 selective enrichment of glycopeptides from complex biological samples 115:183 Although selective enrichment of glycopeptides from complex biological samples is indispensable for mass spectrometry (MS)-based glycoproteomics, it still remains a great challenge due to the low abundance of glycoproteins and suppression of non-glycopeptides. 28071783 1 21 theme selective 115:123 arg1 enrichment 125:134 selective enrichment 115:134 selective enrichment of glycopeptides from complex biological samples 115:183 Although selective enrichment of glycopeptides from complex biological samples is indispensable for mass spectrometry (MS)-based glycoproteomics, it still remains a great challenge due to the low abundance of glycoproteins and suppression of non-glycopeptides. 28071783 5 22 theme enrichment 778:787 arg1 ability 789:795 excellent enrichment ability 768:795 excellent enrichment ability 768:795 GO/Fe3O4/PEI/Ag nanocomposites offered excellent enrichment ability, which was attributed to the synergistic effect of polyethylenimine and silver nanoparticles. 28071783 2 23 theme oxide 435:439 arg1 nanocomposites 441:454 silver nanoparticle-functionalized magnetic graphene oxide nanocomposites 382:454 silver nanoparticle-functionalized magnetic graphene oxide nanocomposites (GO/Fe3O4/PEI/Ag) 382:472 In this study, silver nanoparticle-functionalized magnetic graphene oxide nanocomposites (GO/Fe3O4/PEI/Ag) were synthesized. 28071783 2 23 theme oxide 435:439 arg1 GO/Fe3O4/PEI/Ag 457:471 GO/Fe3O4/PEI/Ag 457:471 GO/Fe3O4/PEI/Ag 457:471 In this study, silver nanoparticle-functionalized magnetic graphene oxide nanocomposites (GO/Fe3O4/PEI/Ag) were synthesized. 28071783 1 24 theme low 298:300 arg1 abundance 302:310 the low abundance 294:310 the low abundance of glycoproteins 294:327 Although selective enrichment of glycopeptides from complex biological samples is indispensable for mass spectrometry (MS)-based glycoproteomics, it still remains a great challenge due to the low abundance of glycoproteins and suppression of non-glycopeptides. 28071783 4 25 gly glycopeptides 714:726 arg2 glycopeptides 714:726 glycopeptides 714:726 glycopeptides 714:726 The resulting material was used as an adsorbent for selective enrichment of glycopeptides. 28071783 7 26 theme rapid 1087:1091 arg1 adsorption 1093:1102 rapid adsorption 1087:1102 rapid adsorption (1 min) 1087:1110 The nanocomposites displayed advantages including rapid adsorption (1 min), low detection limit (25 fmol), repeatability (6 times), and high recovery (77.8%). 28071783 7 26 theme rapid 1087:1091 arg1 min 1107:1109 1 min 1105:1109 1 min 1105:1109 The nanocomposites displayed advantages including rapid adsorption (1 min), low detection limit (25 fmol), repeatability (6 times), and high recovery (77.8%). 28071783 2 27 theme graphene 426:433 arg1 nanocomposites 441:454 silver nanoparticle-functionalized magnetic graphene oxide nanocomposites 382:454 silver nanoparticle-functionalized magnetic graphene oxide nanocomposites (GO/Fe3O4/PEI/Ag) 382:472 In this study, silver nanoparticle-functionalized magnetic graphene oxide nanocomposites (GO/Fe3O4/PEI/Ag) were synthesized. 28071783 2 27 theme graphene 426:433 arg1 GO/Fe3O4/PEI/Ag 457:471 GO/Fe3O4/PEI/Ag 457:471 GO/Fe3O4/PEI/Ag 457:471 In this study, silver nanoparticle-functionalized magnetic graphene oxide nanocomposites (GO/Fe3O4/PEI/Ag) were synthesized. 28071783 8 28 theme N-linked 1259:1266 arg1 glycopeptides 1268:1280 136 N-linked glycopeptides 1255:1280 136 N-linked glycopeptides 1255:1280 Using these nanocomposites, 91 different glycoproteins and 136 N-linked glycopeptides were identified from among 20 μg tryptic human serum proteins and this demonstrated the superior performance of the nanocomposites for glycopeptides enrichment. 28071783 7 29 theme high 1173:1176 arg1 % 1192:1192 77.8% 1188:1192 77.8% 1188:1192 The nanocomposites displayed advantages including rapid adsorption (1 min), low detection limit (25 fmol), repeatability (6 times), and high recovery (77.8%). 28071783 7 29 theme high 1173:1176 arg1 recovery 1178:1185 high recovery 1173:1185 high recovery (77.8%) 1173:1193 The nanocomposites displayed advantages including rapid adsorption (1 min), low detection limit (25 fmol), repeatability (6 times), and high recovery (77.8%). 28071783 3 30 theme stabilizing 619:629 arg1 agent 631:635 a reducing and stabilizing agent 604:635 a reducing and stabilizing agent 604:635 Silver nanoparticles were generated in situ on the surface of magnetic graphene oxide using polyethylenimine as a reducing and stabilizing agent. 28071783 3 30 theme stabilizing 619:629 arg1 polyethylenimine 584:599 polyethylenimine 584:599 polyethylenimine 584:599 Silver nanoparticles were generated in situ on the surface of magnetic graphene oxide using polyethylenimine as a reducing and stabilizing agent. 28071783 1 31 theme -based 228:233 arg1 glycoproteomics 235:249 mass spectrometry (MS)-based glycoproteomics 206:249 mass spectrometry (MS)-based glycoproteomics 206:249 Although selective enrichment of glycopeptides from complex biological samples is indispensable for mass spectrometry (MS)-based glycoproteomics, it still remains a great challenge due to the low abundance of glycoproteins and suppression of non-glycopeptides. 28071783 1 32 theme glycopeptides 139:151 arg1 enrichment 125:134 selective enrichment 115:134 selective enrichment of glycopeptides from complex biological samples 115:183 Although selective enrichment of glycopeptides from complex biological samples is indispensable for mass spectrometry (MS)-based glycoproteomics, it still remains a great challenge due to the low abundance of glycoproteins and suppression of non-glycopeptides. 28071783 4 33 theme selective 690:698 arg1 enrichment 700:709 selective enrichment 690:709 selective enrichment of glycopeptides 690:726 The resulting material was used as an adsorbent for selective enrichment of glycopeptides. 28071783 8 34 theme μg 1312:1313 arg1 serum 1329:1333 20 μg tryptic human serum 1309:1333 20 μg tryptic human serum proteins 1309:1342 Using these nanocomposites, 91 different glycoproteins and 136 N-linked glycopeptides were identified from among 20 μg tryptic human serum proteins and this demonstrated the superior performance of the nanocomposites for glycopeptides enrichment. 28071783 1 35 theme glycoproteins 315:327 arg1 suppression 333:343 suppression 333:343 suppression of non-glycopeptides 333:364 Although selective enrichment of glycopeptides from complex biological samples is indispensable for mass spectrometry (MS)-based glycoproteomics, it still remains a great challenge due to the low abundance of glycoproteins and suppression of non-glycopeptides. 28071783 1 35 theme glycoproteins 315:327 arg1 abundance 302:310 the low abundance 294:310 the low abundance of glycoproteins 294:327 Although selective enrichment of glycopeptides from complex biological samples is indispensable for mass spectrometry (MS)-based glycoproteomics, it still remains a great challenge due to the low abundance of glycoproteins and suppression of non-glycopeptides. 28071783 3 36 theme Silver 492:497 arg1 nanoparticles 499:511 Silver nanoparticles 492:511 Silver nanoparticles 492:511 Silver nanoparticles were generated in situ on the surface of magnetic graphene oxide using polyethylenimine as a reducing and stabilizing agent. 28071783 4 37 theme glycopeptides 714:726 arg1 enrichment 700:709 selective enrichment 690:709 selective enrichment of glycopeptides 690:726 The resulting material was used as an adsorbent for selective enrichment of glycopeptides. 28071783 0 38 theme silver 31:36 arg1 application 16:26 application 16:26 application 16:26 Preparation and application of silver nanoparticle-functionalized magnetic graphene oxide nanocomposites. 28071783 0 38 theme silver 31:36 arg1 Preparation 0:10 Preparation 0:10 Preparation 0:10 Preparation and application of silver nanoparticle-functionalized magnetic graphene oxide nanocomposites. 28071783 4 39 theme resulting 642:650 arg1 adsorbent 676:684 adsorbent 676:684 adsorbent 676:684 The resulting material was used as an adsorbent for selective enrichment of glycopeptides. 28071783 4 39 theme resulting 642:650 arg1 material 652:659 The resulting material 638:659 The resulting material 638:659 The resulting material was used as an adsorbent for selective enrichment of glycopeptides. 28071783 8 40 theme superior 1370:1377 arg1 performance 1379:1389 the superior performance 1366:1389 the superior performance of the nanocomposites for glycopeptides enrichment 1366:1440 Using these nanocomposites, 91 different glycoproteins and 136 N-linked glycopeptides were identified from among 20 μg tryptic human serum proteins and this demonstrated the superior performance of the nanocomposites for glycopeptides enrichment. 28071783 0 41 theme graphene 75:82 arg1 nanocomposites 90:103 magnetic graphene oxide nanocomposites 66:103 magnetic graphene oxide nanocomposites 66:103 Preparation and application of silver nanoparticle-functionalized magnetic graphene oxide nanocomposites. 28071783 6 42 gly glycopeptides 942:954 arg2 glycopeptides 942:954 glycopeptides 942:954 glycopeptides 942:954 The nanocomposites showed superior specificity for glycopeptides even when non-glycopeptides were 100 times more concentrated than glycopeptides. 28071783 5 43 theme excellent 768:776 arg1 ability 789:795 excellent enrichment ability 768:795 excellent enrichment ability 768:795 GO/Fe3O4/PEI/Ag nanocomposites offered excellent enrichment ability, which was attributed to the synergistic effect of polyethylenimine and silver nanoparticles. 28071783 0 44 theme magnetic 66:73 arg1 nanocomposites 90:103 magnetic graphene oxide nanocomposites 66:103 magnetic graphene oxide nanocomposites 66:103 Preparation and application of silver nanoparticle-functionalized magnetic graphene oxide nanocomposites. 28071783 4 45 used used 665:668 arg2 adsorbent 676:684 adsorbent 676:684 adsorbent 676:684 The resulting material was used as an adsorbent for selective enrichment of glycopeptides. 28071783 4 45 used used 665:668 arg2 material 652:659 The resulting material 638:659 The resulting material 638:659 The resulting material was used as an adsorbent for selective enrichment of glycopeptides. 28071783 1 46 gly glycoproteins 315:327 arg1 glycoproteins 315:327 glycoproteins 315:327 glycoproteins 315:327 Although selective enrichment of glycopeptides from complex biological samples is indispensable for mass spectrometry (MS)-based glycoproteomics, it still remains a great challenge due to the low abundance of glycoproteins and suppression of non-glycopeptides. 28071783 1 47 theme complex 158:164 arg1 samples 177:183 complex biological samples 158:183 complex biological samples 158:183 Although selective enrichment of glycopeptides from complex biological samples is indispensable for mass spectrometry (MS)-based glycoproteomics, it still remains a great challenge due to the low abundance of glycoproteins and suppression of non-glycopeptides. 28071783 1 48 theme non-glycopeptides 348:364 arg1 suppression 333:343 suppression 333:343 suppression of non-glycopeptides 333:364 Although selective enrichment of glycopeptides from complex biological samples is indispensable for mass spectrometry (MS)-based glycoproteomics, it still remains a great challenge due to the low abundance of glycoproteins and suppression of non-glycopeptides. 28071783 1 48 theme non-glycopeptides 348:364 arg1 abundance 302:310 the low abundance 294:310 the low abundance of glycoproteins 294:327 Although selective enrichment of glycopeptides from complex biological samples is indispensable for mass spectrometry (MS)-based glycoproteomics, it still remains a great challenge due to the low abundance of glycoproteins and suppression of non-glycopeptides. 28071783 3 49 theme oxide 572:576 arg1 surface 543:549 the surface 539:549 the surface of magnetic graphene oxide using polyethylenimine as a reducing and stabilizing agent 539:635 Silver nanoparticles were generated in situ on the surface of magnetic graphene oxide using polyethylenimine as a reducing and stabilizing agent. 28071783 8 50 gly glycoproteins 1237:1249 arg1 glycoproteins 1237:1249 91 different glycoproteins 1224:1249 91 different glycoproteins 1224:1249 Using these nanocomposites, 91 different glycoproteins and 136 N-linked glycopeptides were identified from among 20 μg tryptic human serum proteins and this demonstrated the superior performance of the nanocomposites for glycopeptides enrichment. 28071783 1 51 theme biological 166:175 arg1 samples 177:183 complex biological samples 158:183 complex biological samples 158:183 Although selective enrichment of glycopeptides from complex biological samples is indispensable for mass spectrometry (MS)-based glycoproteomics, it still remains a great challenge due to the low abundance of glycoproteins and suppression of non-glycopeptides. 28071783 7 52 theme detection 1117:1125 arg1 limit 1127:1131 low detection limit 1113:1131 low detection limit (25 fmol) 1113:1141 The nanocomposites displayed advantages including rapid adsorption (1 min), low detection limit (25 fmol), repeatability (6 times), and high recovery (77.8%). 28071783 7 52 theme detection 1117:1125 arg1 fmol 1137:1140 25 fmol 1134:1140 25 fmol 1134:1140 The nanocomposites displayed advantages including rapid adsorption (1 min), low detection limit (25 fmol), repeatability (6 times), and high recovery (77.8%). 28071783 8 53 theme glycopeptides 1417:1429 arg1 enrichment 1431:1440 glycopeptides enrichment 1417:1440 glycopeptides enrichment 1417:1440 Using these nanocomposites, 91 different glycoproteins and 136 N-linked glycopeptides were identified from among 20 μg tryptic human serum proteins and this demonstrated the superior performance of the nanocomposites for glycopeptides enrichment. 28071783 8 54 theme human 1323:1327 arg1 serum 1329:1333 20 μg tryptic human serum 1309:1333 20 μg tryptic human serum proteins 1309:1342 Using these nanocomposites, 91 different glycoproteins and 136 N-linked glycopeptides were identified from among 20 μg tryptic human serum proteins and this demonstrated the superior performance of the nanocomposites for glycopeptides enrichment. 28071783 8 55 theme 20 1309:1310 arg1 μg 1312:1313 μg 1312:1313 μg 1312:1313 Using these nanocomposites, 91 different glycoproteins and 136 N-linked glycopeptides were identified from among 20 μg tryptic human serum proteins and this demonstrated the superior performance of the nanocomposites for glycopeptides enrichment. 28071783 5 56 theme polyethylenimine 848:863 arg1 effect 838:843 the synergistic effect 822:843 the synergistic effect of polyethylenimine and silver nanoparticles 822:888 GO/Fe3O4/PEI/Ag nanocomposites offered excellent enrichment ability, which was attributed to the synergistic effect of polyethylenimine and silver nanoparticles. 28071783 8 57 link N-linked 1259:1266 arg1 glycopeptides 1268:1280 136 N-linked glycopeptides 1255:1280 136 N-linked glycopeptides 1255:1280 Using these nanocomposites, 91 different glycoproteins and 136 N-linked glycopeptides were identified from among 20 μg tryptic human serum proteins and this demonstrated the superior performance of the nanocomposites for glycopeptides enrichment. 28071783 2 58 theme magnetic 417:424 arg1 nanocomposites 441:454 silver nanoparticle-functionalized magnetic graphene oxide nanocomposites 382:454 silver nanoparticle-functionalized magnetic graphene oxide nanocomposites (GO/Fe3O4/PEI/Ag) 382:472 In this study, silver nanoparticle-functionalized magnetic graphene oxide nanocomposites (GO/Fe3O4/PEI/Ag) were synthesized. 28071783 2 58 theme magnetic 417:424 arg1 GO/Fe3O4/PEI/Ag 457:471 GO/Fe3O4/PEI/Ag 457:471 GO/Fe3O4/PEI/Ag 457:471 In this study, silver nanoparticle-functionalized magnetic graphene oxide nanocomposites (GO/Fe3O4/PEI/Ag) were synthesized. 28071783 6 59 gly glycopeptides 1022:1034 arg2 glycopeptides 1022:1034 glycopeptides 1022:1034 glycopeptides 1022:1034 The nanocomposites showed superior specificity for glycopeptides even when non-glycopeptides were 100 times more concentrated than glycopeptides. 28071783 0 60 theme oxide 84:88 arg1 nanocomposites 90:103 magnetic graphene oxide nanocomposites 66:103 magnetic graphene oxide nanocomposites 66:103 Preparation and application of silver nanoparticle-functionalized magnetic graphene oxide nanocomposites. 28071783 1 61 gly non-glycopeptides 348:364 arg2 non-glycopeptides 348:364 non-glycopeptides 348:364 non-glycopeptides 348:364 Although selective enrichment of glycopeptides from complex biological samples is indispensable for mass spectrometry (MS)-based glycoproteomics, it still remains a great challenge due to the low abundance of glycoproteins and suppression of non-glycopeptides. 28071783 2 62 theme nanoparticle-functionalized 389:415 arg1 nanocomposites 441:454 silver nanoparticle-functionalized magnetic graphene oxide nanocomposites 382:454 silver nanoparticle-functionalized magnetic graphene oxide nanocomposites (GO/Fe3O4/PEI/Ag) 382:472 In this study, silver nanoparticle-functionalized magnetic graphene oxide nanocomposites (GO/Fe3O4/PEI/Ag) were synthesized. 28071783 2 62 theme nanoparticle-functionalized 389:415 arg1 GO/Fe3O4/PEI/Ag 457:471 GO/Fe3O4/PEI/Ag 457:471 GO/Fe3O4/PEI/Ag 457:471 In this study, silver nanoparticle-functionalized magnetic graphene oxide nanocomposites (GO/Fe3O4/PEI/Ag) were synthesized. 28071783 3 63 theme magnetic 554:561 arg1 oxide 572:576 magnetic graphene oxide 554:576 magnetic graphene oxide using polyethylenimine as a reducing and stabilizing agent 554:635 Silver nanoparticles were generated in situ on the surface of magnetic graphene oxide using polyethylenimine as a reducing and stabilizing agent. 28071783 1 64 theme great 271:275 arg1 challenge 277:285 a great challenge 269:285 a great challenge due to the low abundance of glycoproteins and suppression of non-glycopeptides 269:364 Although selective enrichment of glycopeptides from complex biological samples is indispensable for mass spectrometry (MS)-based glycoproteomics, it still remains a great challenge due to the low abundance of glycoproteins and suppression of non-glycopeptides. 26786635 5 0 theme spectrometer 748:759 arg1 analysis 761:768 Gas chromatography-mass spectrometer analysis 724:768 Gas chromatography-mass spectrometer analysis 724:768 Gas chromatography-mass spectrometer analysis showed that its sugar component was galactose. 26786635 1 1 theme sulfate 225:231 arg1 precipitation 233:245 ammonium sulfate precipitation 216:245 ammonium sulfate precipitation 216:245 A soluble glycoprotein was purified to homogeneity from ripe garlic (Allium sativum) bulbs using ammonium sulfate precipitation, Sephadex G-100 gel filtration, and diethylaminoethyl-52 cellulose anion-exchange chromatography. 26786635 7 2 contain has 1018:1020 arg2 potential 1022:1030 potential 1022:1030 potential for food additives, functional foods, and even biotechnological and medical applications 1022:1119 These results indicated that the glycoprotein has potential for food additives, functional foods, and even biotechnological and medical applications. 26786635 7 2 contain has 1018:1020 arg1 glycoprotein 1005:1016 the glycoprotein 1001:1016 the glycoprotein 1001:1016 These results indicated that the glycoprotein has potential for food additives, functional foods, and even biotechnological and medical applications. 26786635 5 3 theme Gas 724:726 arg1 analysis 761:768 Gas chromatography-mass spectrometer analysis 724:768 Gas chromatography-mass spectrometer analysis 724:768 Gas chromatography-mass spectrometer analysis showed that its sugar component was galactose. 26786635 7 4 theme even 1074:1077 arg1 applications 1108:1119 even biotechnological and medical applications 1074:1119 even biotechnological and medical applications 1074:1119 These results indicated that the glycoprotein has potential for food additives, functional foods, and even biotechnological and medical applications. 26786635 0 5 dep in 97:98 arg1 vitro 100:104 vitro 100:104 vitro 100:104 Purification and characterization of a soluble glycoprotein from garlic (Allium sativum) and its in vitro bioactivity. 26786635 5 6 theme chromatography-mass 728:746 arg1 analysis 761:768 Gas chromatography-mass spectrometer analysis 724:768 Gas chromatography-mass spectrometer analysis 724:768 Gas chromatography-mass spectrometer analysis showed that its sugar component was galactose. 26786635 6 7 theme inhibition 922:931 arg1 ability 933:939 the peroxidation inhibition ability 905:939 the peroxidation inhibition ability to polyunsaturated fatty acid 905:969 The glycoprotein has 1,1-diphenyl-2-picrylhydrazil free radical scavenging activity and the peroxidation inhibition ability to polyunsaturated fatty acid. 26786635 1 8 theme Sephadex 248:255 arg1 filtration 267:276 Sephadex G-100 gel filtration 248:276 Sephadex G-100 gel filtration 248:276 A soluble glycoprotein was purified to homogeneity from ripe garlic (Allium sativum) bulbs using ammonium sulfate precipitation, Sephadex G-100 gel filtration, and diethylaminoethyl-52 cellulose anion-exchange chromatography. 26786635 0 9 theme in 97:98 arg1 bioactivity 106:116 its in vitro bioactivity 93:116 its in vitro bioactivity 93:116 Purification and characterization of a soluble glycoprotein from garlic (Allium sativum) and its in vitro bioactivity. 26786635 3 10 gly glycoprotein 619:630 arg1 type 647:650 an N-linked type 635:650 an N-linked type 635:650 β-Elimination reaction result suggested that the glycoprotein is an N-linked type. 26786635 3 10 gly glycoprotein 619:630 arg1 glycoprotein 619:630 the glycoprotein 615:630 the glycoprotein 615:630 β-Elimination reaction result suggested that the glycoprotein is an N-linked type. 26786635 6 11 theme peroxidation 909:920 arg1 ability 933:939 the peroxidation inhibition ability 905:939 the peroxidation inhibition ability to polyunsaturated fatty acid 905:969 The glycoprotein has 1,1-diphenyl-2-picrylhydrazil free radical scavenging activity and the peroxidation inhibition ability to polyunsaturated fatty acid. 26786635 2 12 gly glycoprotein 538:549 arg1 glycoprotein 538:549 the glycoprotein 534:549 the glycoprotein 534:549 A native mass of 55.7 kDa estimated on gel permeation chromatography and a molecular weight of 13.2 kDa observed on sodium dodecyl sulfate-polyacrylamide gel electrophoresis supported that the glycoprotein is a homotetramer. 26786635 2 12 gly glycoprotein 538:549 arg1 homotetramer 556:567 a homotetramer 554:567 a homotetramer 554:567 A native mass of 55.7 kDa estimated on gel permeation chromatography and a molecular weight of 13.2 kDa observed on sodium dodecyl sulfate-polyacrylamide gel electrophoresis supported that the glycoprotein is a homotetramer. 26786635 0 13 theme soluble 39:45 arg1 glycoprotein 47:58 a soluble glycoprotein 37:58 a soluble glycoprotein 37:58 Purification and characterization of a soluble glycoprotein from garlic (Allium sativum) and its in vitro bioactivity. 26786635 2 14 located observed 449:456 arg1 electrophoresis 503:517 sodium dodecyl sulfate-polyacrylamide gel electrophoresis 461:517 sodium dodecyl sulfate-polyacrylamide gel electrophoresis 461:517 A native mass of 55.7 kDa estimated on gel permeation chromatography and a molecular weight of 13.2 kDa observed on sodium dodecyl sulfate-polyacrylamide gel electrophoresis supported that the glycoprotein is a homotetramer. 26786635 2 14 located observed 449:456 arg2 13.2 kDa 440:447 13.2 kDa 440:447 13.2 kDa observed on sodium dodecyl sulfate-polyacrylamide gel electrophoresis 440:517 A native mass of 55.7 kDa estimated on gel permeation chromatography and a molecular weight of 13.2 kDa observed on sodium dodecyl sulfate-polyacrylamide gel electrophoresis supported that the glycoprotein is a homotetramer. 26786635 3 15 theme β-Elimination 570:582 arg1 result 593:598 β-Elimination reaction result 570:598 β-Elimination reaction result 570:598 β-Elimination reaction result suggested that the glycoprotein is an N-linked type. 26786635 2 16 theme permeation 388:397 arg1 chromatography 399:412 gel permeation chromatography 384:412 gel permeation chromatography 384:412 A native mass of 55.7 kDa estimated on gel permeation chromatography and a molecular weight of 13.2 kDa observed on sodium dodecyl sulfate-polyacrylamide gel electrophoresis supported that the glycoprotein is a homotetramer. 26786635 6 17 contain has 834:836 arg1 glycoprotein 821:832 The glycoprotein 817:832 The glycoprotein 817:832 The glycoprotein has 1,1-diphenyl-2-picrylhydrazil free radical scavenging activity and the peroxidation inhibition ability to polyunsaturated fatty acid. 26786635 6 17 contain has 834:836 arg2 ability 933:939 the peroxidation inhibition ability 905:939 the peroxidation inhibition ability to polyunsaturated fatty acid 905:969 The glycoprotein has 1,1-diphenyl-2-picrylhydrazil free radical scavenging activity and the peroxidation inhibition ability to polyunsaturated fatty acid. 26786635 6 17 contain has 834:836 arg2 activity 892:899 1,1-diphenyl-2-picrylhydrazil free radical scavenging activity 838:899 1,1-diphenyl-2-picrylhydrazil free radical scavenging activity 838:899 The glycoprotein has 1,1-diphenyl-2-picrylhydrazil free radical scavenging activity and the peroxidation inhibition ability to polyunsaturated fatty acid. 26786635 2 18 theme gel 384:386 arg1 chromatography 399:412 gel permeation chromatography 384:412 gel permeation chromatography 384:412 A native mass of 55.7 kDa estimated on gel permeation chromatography and a molecular weight of 13.2 kDa observed on sodium dodecyl sulfate-polyacrylamide gel electrophoresis supported that the glycoprotein is a homotetramer. 26786635 1 19 theme G-100 257:261 arg1 filtration 267:276 Sephadex G-100 gel filtration 248:276 Sephadex G-100 gel filtration 248:276 A soluble glycoprotein was purified to homogeneity from ripe garlic (Allium sativum) bulbs using ammonium sulfate precipitation, Sephadex G-100 gel filtration, and diethylaminoethyl-52 cellulose anion-exchange chromatography. 26786635 7 20 theme functional 1052:1061 arg1 foods 1063:1067 functional foods 1052:1067 functional foods 1052:1067 These results indicated that the glycoprotein has potential for food additives, functional foods, and even biotechnological and medical applications. 26786635 0 21 dep Allium 73:78 arg1 sativum 80:86 Allium sativum 73:86 Allium sativum 73:86 Purification and characterization of a soluble glycoprotein from garlic (Allium sativum) and its in vitro bioactivity. 26786635 1 22 theme ripe 175:178 arg1 Allium 188:193 Allium 188:193 Allium 188:193 A soluble glycoprotein was purified to homogeneity from ripe garlic (Allium sativum) bulbs using ammonium sulfate precipitation, Sephadex G-100 gel filtration, and diethylaminoethyl-52 cellulose anion-exchange chromatography. 26786635 1 22 theme ripe 175:178 arg1 garlic 180:185 ripe garlic 175:185 ripe garlic (Allium sativum) bulbs using ammonium sulfate precipitation, Sephadex G-100 gel filtration, and diethylaminoethyl-52 cellulose anion-exchange chromatography 175:342 A soluble glycoprotein was purified to homogeneity from ripe garlic (Allium sativum) bulbs using ammonium sulfate precipitation, Sephadex G-100 gel filtration, and diethylaminoethyl-52 cellulose anion-exchange chromatography. 26786635 2 23 theme 13.2 kDa 440:447 arg1 mass 354:357 A native mass 345:357 A native mass of 55.7 kDa estimated on gel permeation chromatography 345:412 A native mass of 55.7 kDa estimated on gel permeation chromatography and a molecular weight of 13.2 kDa observed on sodium dodecyl sulfate-polyacrylamide gel electrophoresis supported that the glycoprotein is a homotetramer. 26786635 2 23 theme 13.2 kDa 440:447 arg1 weight 430:435 a molecular weight 418:435 a molecular weight of 13.2 kDa observed on sodium dodecyl sulfate-polyacrylamide gel electrophoresis 418:517 A native mass of 55.7 kDa estimated on gel permeation chromatography and a molecular weight of 13.2 kDa observed on sodium dodecyl sulfate-polyacrylamide gel electrophoresis supported that the glycoprotein is a homotetramer. 26786635 1 24 theme gel 263:265 arg1 filtration 267:276 Sephadex G-100 gel filtration 248:276 Sephadex G-100 gel filtration 248:276 A soluble glycoprotein was purified to homogeneity from ripe garlic (Allium sativum) bulbs using ammonium sulfate precipitation, Sephadex G-100 gel filtration, and diethylaminoethyl-52 cellulose anion-exchange chromatography. 26786635 6 25 theme scavenging 881:890 arg1 activity 892:899 1,1-diphenyl-2-picrylhydrazil free radical scavenging activity 838:899 1,1-diphenyl-2-picrylhydrazil free radical scavenging activity 838:899 The glycoprotein has 1,1-diphenyl-2-picrylhydrazil free radical scavenging activity and the peroxidation inhibition ability to polyunsaturated fatty acid. 26786635 1 26 theme garlic 180:185 arg1 bulbs 204:208 ripe garlic (Allium sativum) bulbs 175:208 ripe garlic (Allium sativum) bulbs using ammonium sulfate precipitation, Sephadex G-100 gel filtration, and diethylaminoethyl-52 cellulose anion-exchange chromatography 175:342 A soluble glycoprotein was purified to homogeneity from ripe garlic (Allium sativum) bulbs using ammonium sulfate precipitation, Sephadex G-100 gel filtration, and diethylaminoethyl-52 cellulose anion-exchange chromatography. 26786635 5 27 theme sugar 786:790 arg1 component 792:800 its sugar component 782:800 its sugar component 782:800 Gas chromatography-mass spectrometer analysis showed that its sugar component was galactose. 26786635 7 28 theme biotechnological 1079:1094 arg1 applications 1108:1119 even biotechnological and medical applications 1074:1119 even biotechnological and medical applications 1074:1119 These results indicated that the glycoprotein has potential for food additives, functional foods, and even biotechnological and medical applications. 26786635 2 29 theme molecular 420:428 arg1 weight 430:435 a molecular weight 418:435 a molecular weight of 13.2 kDa observed on sodium dodecyl sulfate-polyacrylamide gel electrophoresis 418:517 A native mass of 55.7 kDa estimated on gel permeation chromatography and a molecular weight of 13.2 kDa observed on sodium dodecyl sulfate-polyacrylamide gel electrophoresis supported that the glycoprotein is a homotetramer. 26786635 2 30 theme gel 499:501 arg1 electrophoresis 503:517 sodium dodecyl sulfate-polyacrylamide gel electrophoresis 461:517 sodium dodecyl sulfate-polyacrylamide gel electrophoresis 461:517 A native mass of 55.7 kDa estimated on gel permeation chromatography and a molecular weight of 13.2 kDa observed on sodium dodecyl sulfate-polyacrylamide gel electrophoresis supported that the glycoprotein is a homotetramer. 26786635 4 31 contain contains 708:715 arg1 it 705:706 it 705:706 it 705:706 Fourier-transform infrared spectroscopy proved that it contains sugar. 26786635 4 31 contain contains 708:715 arg2 sugar 717:721 sugar 717:721 sugar 717:721 Fourier-transform infrared spectroscopy proved that it contains sugar. 26786635 3 32 theme N-linked 638:645 arg1 type 647:650 an N-linked type 635:650 an N-linked type 635:650 β-Elimination reaction result suggested that the glycoprotein is an N-linked type. 26786635 3 32 theme N-linked 638:645 arg1 glycoprotein 619:630 the glycoprotein 615:630 the glycoprotein 615:630 β-Elimination reaction result suggested that the glycoprotein is an N-linked type. 26786635 2 33 theme sulfate-polyacrylamide 476:497 arg1 electrophoresis 503:517 sodium dodecyl sulfate-polyacrylamide gel electrophoresis 461:517 sodium dodecyl sulfate-polyacrylamide gel electrophoresis 461:517 A native mass of 55.7 kDa estimated on gel permeation chromatography and a molecular weight of 13.2 kDa observed on sodium dodecyl sulfate-polyacrylamide gel electrophoresis supported that the glycoprotein is a homotetramer. 26786635 7 34 gly glycoprotein 1005:1016 arg1 glycoprotein 1005:1016 the glycoprotein 1001:1016 the glycoprotein 1001:1016 These results indicated that the glycoprotein has potential for food additives, functional foods, and even biotechnological and medical applications. 26786635 6 35 theme radical 873:879 arg1 activity 892:899 1,1-diphenyl-2-picrylhydrazil free radical scavenging activity 838:899 1,1-diphenyl-2-picrylhydrazil free radical scavenging activity 838:899 The glycoprotein has 1,1-diphenyl-2-picrylhydrazil free radical scavenging activity and the peroxidation inhibition ability to polyunsaturated fatty acid. 26786635 3 36 link N-linked 638:645 arg1 type 647:650 an N-linked type 635:650 an N-linked type 635:650 β-Elimination reaction result suggested that the glycoprotein is an N-linked type. 26786635 3 36 link N-linked 638:645 arg1 glycoprotein 619:630 the glycoprotein 615:630 the glycoprotein 615:630 β-Elimination reaction result suggested that the glycoprotein is an N-linked type. 26786635 1 37 gly glycoprotein 129:140 arg1 glycoprotein 129:140 A soluble glycoprotein 119:140 A soluble glycoprotein 119:140 A soluble glycoprotein was purified to homogeneity from ripe garlic (Allium sativum) bulbs using ammonium sulfate precipitation, Sephadex G-100 gel filtration, and diethylaminoethyl-52 cellulose anion-exchange chromatography. 26786635 0 38 from garlic 65:70 arg1 characterization 17:32 characterization 17:32 characterization 17:32 Purification and characterization of a soluble glycoprotein from garlic (Allium sativum) and its in vitro bioactivity. 26786635 0 38 from garlic 65:70 arg1 Purification 0:11 Purification 0:11 Purification 0:11 Purification and characterization of a soluble glycoprotein from garlic (Allium sativum) and its in vitro bioactivity. 26786635 0 38 from garlic 65:70 arg1 bioactivity 106:116 its in vitro bioactivity 93:116 its in vitro bioactivity 93:116 Purification and characterization of a soluble glycoprotein from garlic (Allium sativum) and its in vitro bioactivity. 26786635 6 39 theme free 868:871 arg1 radical 873:879 1,1-diphenyl-2-picrylhydrazil free radical 838:879 1,1-diphenyl-2-picrylhydrazil free radical scavenging activity 838:899 The glycoprotein has 1,1-diphenyl-2-picrylhydrazil free radical scavenging activity and the peroxidation inhibition ability to polyunsaturated fatty acid. 26786635 2 40 theme native 347:352 arg1 mass 354:357 A native mass 345:357 A native mass of 55.7 kDa estimated on gel permeation chromatography 345:412 A native mass of 55.7 kDa estimated on gel permeation chromatography and a molecular weight of 13.2 kDa observed on sodium dodecyl sulfate-polyacrylamide gel electrophoresis supported that the glycoprotein is a homotetramer. 26786635 0 41 theme glycoprotein 47:58 arg1 characterization 17:32 characterization 17:32 characterization 17:32 Purification and characterization of a soluble glycoprotein from garlic (Allium sativum) and its in vitro bioactivity. 26786635 0 41 theme glycoprotein 47:58 arg1 Purification 0:11 Purification 0:11 Purification 0:11 Purification and characterization of a soluble glycoprotein from garlic (Allium sativum) and its in vitro bioactivity. 26786635 0 41 theme glycoprotein 47:58 arg1 bioactivity 106:116 its in vitro bioactivity 93:116 its in vitro bioactivity 93:116 Purification and characterization of a soluble glycoprotein from garlic (Allium sativum) and its in vitro bioactivity. 26786635 1 42 theme cellulose 304:312 arg1 chromatography 329:342 diethylaminoethyl-52 cellulose anion-exchange chromatography 283:342 diethylaminoethyl-52 cellulose anion-exchange chromatography 283:342 A soluble glycoprotein was purified to homogeneity from ripe garlic (Allium sativum) bulbs using ammonium sulfate precipitation, Sephadex G-100 gel filtration, and diethylaminoethyl-52 cellulose anion-exchange chromatography. 26786635 6 43 theme 1,1-diphenyl-2-picrylhydrazil 838:866 arg1 radical 873:879 1,1-diphenyl-2-picrylhydrazil free radical 838:879 1,1-diphenyl-2-picrylhydrazil free radical scavenging activity 838:899 The glycoprotein has 1,1-diphenyl-2-picrylhydrazil free radical scavenging activity and the peroxidation inhibition ability to polyunsaturated fatty acid. 26786635 1 44 theme anion-exchange 314:327 arg1 chromatography 329:342 diethylaminoethyl-52 cellulose anion-exchange chromatography 283:342 diethylaminoethyl-52 cellulose anion-exchange chromatography 283:342 A soluble glycoprotein was purified to homogeneity from ripe garlic (Allium sativum) bulbs using ammonium sulfate precipitation, Sephadex G-100 gel filtration, and diethylaminoethyl-52 cellulose anion-exchange chromatography. 26786635 1 45 dep Allium 188:193 arg1 sativum 195:201 Allium sativum 188:201 Allium sativum 188:201 A soluble glycoprotein was purified to homogeneity from ripe garlic (Allium sativum) bulbs using ammonium sulfate precipitation, Sephadex G-100 gel filtration, and diethylaminoethyl-52 cellulose anion-exchange chromatography. 26786635 7 46 theme medical 1100:1106 arg1 applications 1108:1119 even biotechnological and medical applications 1074:1119 even biotechnological and medical applications 1074:1119 These results indicated that the glycoprotein has potential for food additives, functional foods, and even biotechnological and medical applications. 26786635 4 47 theme Fourier-transform 653:669 arg1 spectroscopy 680:691 Fourier-transform infrared spectroscopy 653:691 Fourier-transform infrared spectroscopy 653:691 Fourier-transform infrared spectroscopy proved that it contains sugar. 26786635 6 48 theme fatty 960:964 arg1 acid 966:969 polyunsaturated fatty acid 944:969 polyunsaturated fatty acid 944:969 The glycoprotein has 1,1-diphenyl-2-picrylhydrazil free radical scavenging activity and the peroxidation inhibition ability to polyunsaturated fatty acid. 26786635 3 49 theme reaction 584:591 arg1 result 593:598 β-Elimination reaction result 570:598 β-Elimination reaction result 570:598 β-Elimination reaction result suggested that the glycoprotein is an N-linked type. 26786635 6 50 gly glycoprotein 821:832 arg1 glycoprotein 821:832 The glycoprotein 817:832 The glycoprotein 817:832 The glycoprotein has 1,1-diphenyl-2-picrylhydrazil free radical scavenging activity and the peroxidation inhibition ability to polyunsaturated fatty acid. 26786635 6 51 theme polyunsaturated 944:958 arg1 acid 966:969 polyunsaturated fatty acid 944:969 polyunsaturated fatty acid 944:969 The glycoprotein has 1,1-diphenyl-2-picrylhydrazil free radical scavenging activity and the peroxidation inhibition ability to polyunsaturated fatty acid. 26786635 0 52 gly glycoprotein 47:58 arg1 glycoprotein 47:58 a soluble glycoprotein 37:58 a soluble glycoprotein 37:58 Purification and characterization of a soluble glycoprotein from garlic (Allium sativum) and its in vitro bioactivity. 26786635 1 53 theme soluble 121:127 arg1 glycoprotein 129:140 A soluble glycoprotein 119:140 A soluble glycoprotein 119:140 A soluble glycoprotein was purified to homogeneity from ripe garlic (Allium sativum) bulbs using ammonium sulfate precipitation, Sephadex G-100 gel filtration, and diethylaminoethyl-52 cellulose anion-exchange chromatography. 26786635 7 54 theme food 1036:1039 arg1 additives 1041:1049 food additives 1036:1049 food additives 1036:1049 These results indicated that the glycoprotein has potential for food additives, functional foods, and even biotechnological and medical applications. 26786635 4 55 theme infrared 671:678 arg1 spectroscopy 680:691 Fourier-transform infrared spectroscopy 653:691 Fourier-transform infrared spectroscopy 653:691 Fourier-transform infrared spectroscopy proved that it contains sugar. 26786635 2 56 theme 55.7 kDa 362:369 arg1 mass 354:357 A native mass 345:357 A native mass of 55.7 kDa estimated on gel permeation chromatography 345:412 A native mass of 55.7 kDa estimated on gel permeation chromatography and a molecular weight of 13.2 kDa observed on sodium dodecyl sulfate-polyacrylamide gel electrophoresis supported that the glycoprotein is a homotetramer. 26786635 2 56 theme 55.7 kDa 362:369 arg1 weight 430:435 a molecular weight 418:435 a molecular weight of 13.2 kDa observed on sodium dodecyl sulfate-polyacrylamide gel electrophoresis 418:517 A native mass of 55.7 kDa estimated on gel permeation chromatography and a molecular weight of 13.2 kDa observed on sodium dodecyl sulfate-polyacrylamide gel electrophoresis supported that the glycoprotein is a homotetramer. 26786635 1 57 theme ammonium 216:223 arg1 precipitation 233:245 ammonium sulfate precipitation 216:245 ammonium sulfate precipitation 216:245 A soluble glycoprotein was purified to homogeneity from ripe garlic (Allium sativum) bulbs using ammonium sulfate precipitation, Sephadex G-100 gel filtration, and diethylaminoethyl-52 cellulose anion-exchange chromatography. 25598792 8 0 theme genotype 1565:1572 arg1 5a 1574:1575 genotype 5a 1565:1575 genotype 5a 1565:1575 CONCLUSIONS This study provided conserved B-cell epitopes and peptides that can be useful for designing entry inhibitors and vaccines able to cover a global population, especially where genotype 5a is common. 25598792 6 1 theme RESULTS 1121:1127 arg1 Differences 1129:1139 RESULTS Differences 1121:1139 RESULTS Differences in the probability of glycosylation in E1 and E2 regions 1121:1196 RESULTS Differences in the probability of glycosylation in E1 and E2 regions were observed in this study. 25598792 1 2 with people 260:265 arg1 infection 272:280 infection 272:280 infection 272:280 BACKGROUND Hepatitis C virus (HCV) is one of the major causes of cirrhosis and hepatocellular carcinoma with an estimation of 185 million people with infection. 25598792 1 3 theme causes 177:182 arg1 causes 177:182 the major causes 167:182 the major causes of cirrhosis and hepatocellular carcinoma with an estimation of 185 million people with infection 167:280 BACKGROUND Hepatitis C virus (HCV) is one of the major causes of cirrhosis and hepatocellular carcinoma with an estimation of 185 million people with infection. 25598792 1 3 theme causes 177:182 arg1 one 160:162 one 160:162 one 160:162 BACKGROUND Hepatitis C virus (HCV) is one of the major causes of cirrhosis and hepatocellular carcinoma with an estimation of 185 million people with infection. 25598792 6 4 theme E1 1180:1181 arg1 regions 1190:1196 E1 and E2 regions 1180:1196 E1 and E2 regions 1180:1196 RESULTS Differences in the probability of glycosylation in E1 and E2 regions were observed in this study. 25598792 1 5 theme cirrhosis 187:195 arg1 causes 177:182 the major causes 167:182 the major causes of cirrhosis and hepatocellular carcinoma with an estimation of 185 million people with infection 167:280 BACKGROUND Hepatitis C virus (HCV) is one of the major causes of cirrhosis and hepatocellular carcinoma with an estimation of 185 million people with infection. 25598792 4 6 theme vaccine 847:853 arg1 design 837:842 design 837:842 design of vaccine and entry inhibitors 837:874 OBJECTIVES The objective of this study was to characterize genotype 5a E1 and E2 sequences to determine possible glycosylation sites, conserved B-cell epitopes and peptides in HCV that could be useful targets in design of vaccine and entry inhibitors. 25598792 6 7 theme glycosylation 1163:1175 arg1 probability 1148:1158 the probability 1144:1158 the probability of glycosylation in E1 and E2 regions 1144:1196 RESULTS Differences in the probability of glycosylation in E1 and E2 regions were observed in this study. 25598792 1 8 theme BACKGROUND 122:131 arg1 HCV 152:154 HCV 152:154 HCV 152:154 BACKGROUND Hepatitis C virus (HCV) is one of the major causes of cirrhosis and hepatocellular carcinoma with an estimation of 185 million people with infection. 25598792 1 8 theme BACKGROUND 122:131 arg1 virus 145:149 BACKGROUND Hepatitis C virus 122:149 BACKGROUND Hepatitis C virus (HCV) 122:155 BACKGROUND Hepatitis C virus (HCV) is one of the major causes of cirrhosis and hepatocellular carcinoma with an estimation of 185 million people with infection. 25598792 4 9 theme entry 859:863 arg1 inhibitors 865:874 entry inhibitors 859:874 entry inhibitors 859:874 OBJECTIVES The objective of this study was to characterize genotype 5a E1 and E2 sequences to determine possible glycosylation sites, conserved B-cell epitopes and peptides in HCV that could be useful targets in design of vaccine and entry inhibitors. 25598792 7 10 theme E2 1291:1292 arg1 regions 1294:1300 the E2 regions 1287:1300 the E2 regions 1287:1300 Three conserved antigenic B-cell epitopes were predicted in the E2 regions and also 11 short peptides were designed from the highly conserved residues. 25598792 4 11 theme 5a 693:694 arg1 E1 696:697 genotype 5a E1 684:697 genotype 5a E1 684:697 OBJECTIVES The objective of this study was to characterize genotype 5a E1 and E2 sequences to determine possible glycosylation sites, conserved B-cell epitopes and peptides in HCV that could be useful targets in design of vaccine and entry inhibitors. 25598792 3 12 from hypervariable 530:542 arg1 nature 547:552 nature 547:552 nature 547:552 While both E1 and E2 are hypervariable in nature, it is difficult to design vaccines or therapeutic drugs against them. 25598792 5 13 theme B-cell 997:1002 arg1 epitopes 1004:1011 B-cell epitopes 997:1011 B-cell epitopes 997:1011 PATIENTS AND METHODS This study was conducted through PCR amplification of E1 and E2 regions, sequencing, prediction of B-cell epitopes, analysis of N-linked glycosylation and peptide design in 18 samples of HCV genotype 5a from South African. 25598792 7 14 theme conserved 1359:1367 arg1 residues 1369:1376 the highly conserved residues 1348:1376 the highly conserved residues 1348:1376 Three conserved antigenic B-cell epitopes were predicted in the E2 regions and also 11 short peptides were designed from the highly conserved residues. 25598792 1 15 theme C 143:143 arg1 HCV 152:154 HCV 152:154 HCV 152:154 BACKGROUND Hepatitis C virus (HCV) is one of the major causes of cirrhosis and hepatocellular carcinoma with an estimation of 185 million people with infection. 25598792 1 15 theme C 143:143 arg1 virus 145:149 BACKGROUND Hepatitis C virus 122:149 BACKGROUND Hepatitis C virus (HCV) 122:155 BACKGROUND Hepatitis C virus (HCV) is one of the major causes of cirrhosis and hepatocellular carcinoma with an estimation of 185 million people with infection. 25598792 8 16 theme B-cell 1421:1426 arg1 epitopes 1428:1435 conserved B-cell epitopes 1411:1435 conserved B-cell epitopes 1411:1435 CONCLUSIONS This study provided conserved B-cell epitopes and peptides that can be useful for designing entry inhibitors and vaccines able to cover a global population, especially where genotype 5a is common. 25598792 3 17 from nature 547:552 arg1 hypervariable 530:542 hypervariable 530:542 hypervariable 530:542 While both E1 and E2 are hypervariable in nature, it is difficult to design vaccines or therapeutic drugs against them. 25598792 3 18 theme design 574:579 arg1 vaccines 581:588 design vaccines 574:588 design vaccines 574:588 While both E1 and E2 are hypervariable in nature, it is difficult to design vaccines or therapeutic drugs against them. 25598792 2 19 theme subsequent 460:469 arg1 development 471:481 subsequent development 460:481 subsequent development of chronic infection 460:502 The E2 is the main target for neutralizing antibody responses and the variation of this region is related to maintenance of persistent infection by emerging escape variants and subsequent development of chronic infection. 25598792 6 20 from Differences 1129:1139 arg1 probability 1148:1158 the probability 1144:1158 the probability of glycosylation in E1 and E2 regions 1144:1196 RESULTS Differences in the probability of glycosylation in E1 and E2 regions were observed in this study. 25598792 0 21 theme vaccine 72:78 arg1 development 80:90 vaccine development 72:90 vaccine development 72:90 Characterization of HCV genotype 5a envelope proteins: implications for vaccine development and therapeutic entry target. 25598792 4 22 from targets 826:832 arg1 design 837:842 design 837:842 design of vaccine and entry inhibitors 837:874 OBJECTIVES The objective of this study was to characterize genotype 5a E1 and E2 sequences to determine possible glycosylation sites, conserved B-cell epitopes and peptides in HCV that could be useful targets in design of vaccine and entry inhibitors. 25598792 5 23 dep PATIENTS 877:884 arg1 study 903:907 This study 898:907 PATIENTS AND METHODS This study 877:907 PATIENTS AND METHODS This study was conducted through PCR amplification of E1 and E2 regions, sequencing, prediction of B-cell epitopes, analysis of N-linked glycosylation and peptide design in 18 samples of HCV genotype 5a from South African. 25598792 5 24 theme glycosylation 1035:1047 arg1 analysis 1014:1021 analysis 1014:1021 analysis of N-linked glycosylation 1014:1047 PATIENTS AND METHODS This study was conducted through PCR amplification of E1 and E2 regions, sequencing, prediction of B-cell epitopes, analysis of N-linked glycosylation and peptide design in 18 samples of HCV genotype 5a from South African. 25598792 5 24 theme glycosylation 1035:1047 arg1 prediction 983:992 prediction 983:992 prediction of B-cell epitopes 983:1011 PATIENTS AND METHODS This study was conducted through PCR amplification of E1 and E2 regions, sequencing, prediction of B-cell epitopes, analysis of N-linked glycosylation and peptide design in 18 samples of HCV genotype 5a from South African. 25598792 5 24 theme glycosylation 1035:1047 arg1 design 1061:1066 peptide design 1053:1066 peptide design 1053:1066 PATIENTS AND METHODS This study was conducted through PCR amplification of E1 and E2 regions, sequencing, prediction of B-cell epitopes, analysis of N-linked glycosylation and peptide design in 18 samples of HCV genotype 5a from South African. 25598792 5 24 theme glycosylation 1035:1047 arg1 sequencing 971:980 sequencing 971:980 sequencing 971:980 PATIENTS AND METHODS This study was conducted through PCR amplification of E1 and E2 regions, sequencing, prediction of B-cell epitopes, analysis of N-linked glycosylation and peptide design in 18 samples of HCV genotype 5a from South African. 25598792 5 24 theme glycosylation 1035:1047 arg1 amplification 935:947 PCR amplification 931:947 PCR amplification of E1 and E2 regions 931:968 PATIENTS AND METHODS This study was conducted through PCR amplification of E1 and E2 regions, sequencing, prediction of B-cell epitopes, analysis of N-linked glycosylation and peptide design in 18 samples of HCV genotype 5a from South African. 25598792 2 25 theme infection 494:502 arg1 development 471:481 subsequent development 460:481 subsequent development of chronic infection 460:502 The E2 is the main target for neutralizing antibody responses and the variation of this region is related to maintenance of persistent infection by emerging escape variants and subsequent development of chronic infection. 25598792 2 25 theme infection 494:502 arg1 infection 418:426 persistent infection 407:426 persistent infection by emerging escape variants 407:454 The E2 is the main target for neutralizing antibody responses and the variation of this region is related to maintenance of persistent infection by emerging escape variants and subsequent development of chronic infection. 25598792 4 26 theme glycosylation 738:750 arg1 sites 752:756 possible glycosylation sites 729:756 possible glycosylation sites 729:756 OBJECTIVES The objective of this study was to characterize genotype 5a E1 and E2 sequences to determine possible glycosylation sites, conserved B-cell epitopes and peptides in HCV that could be useful targets in design of vaccine and entry inhibitors. 25598792 0 27 theme entry 108:112 arg1 target 114:119 therapeutic entry target 96:119 therapeutic entry target 96:119 Characterization of HCV genotype 5a envelope proteins: implications for vaccine development and therapeutic entry target. 25598792 5 28 theme peptide 1053:1059 arg1 design 1061:1066 peptide design 1053:1066 peptide design 1053:1066 PATIENTS AND METHODS This study was conducted through PCR amplification of E1 and E2 regions, sequencing, prediction of B-cell epitopes, analysis of N-linked glycosylation and peptide design in 18 samples of HCV genotype 5a from South African. 25598792 2 29 theme infection 418:426 arg1 maintenance 392:402 maintenance 392:402 maintenance of persistent infection by emerging escape variants and subsequent development of chronic infection 392:502 The E2 is the main target for neutralizing antibody responses and the variation of this region is related to maintenance of persistent infection by emerging escape variants and subsequent development of chronic infection. 25598792 1 30 theme million 252:258 arg1 people 260:265 185 million people 248:265 185 million people with infection 248:280 BACKGROUND Hepatitis C virus (HCV) is one of the major causes of cirrhosis and hepatocellular carcinoma with an estimation of 185 million people with infection. 25598792 8 31 theme entry 1483:1487 arg1 inhibitors 1489:1498 entry inhibitors 1483:1498 entry inhibitors 1483:1498 CONCLUSIONS This study provided conserved B-cell epitopes and peptides that can be useful for designing entry inhibitors and vaccines able to cover a global population, especially where genotype 5a is common. 25598792 0 32 theme HCV 20:22 arg1 proteins 45:52 HCV genotype 5a envelope proteins 20:52 HCV genotype 5a envelope proteins 20:52 Characterization of HCV genotype 5a envelope proteins: implications for vaccine development and therapeutic entry target. 25598792 6 33 located observed 1203:1210 arg2 Differences 1129:1139 RESULTS Differences 1121:1139 RESULTS Differences in the probability of glycosylation in E1 and E2 regions 1121:1196 RESULTS Differences in the probability of glycosylation in E1 and E2 regions were observed in this study. 25598792 6 33 located observed 1203:1210 arg1 study 1220:1224 this study 1215:1224 this study 1215:1224 RESULTS Differences in the probability of glycosylation in E1 and E2 regions were observed in this study. 25598792 7 34 theme antigenic 1243:1251 arg1 epitopes 1260:1267 Three conserved antigenic B-cell epitopes 1227:1267 Three conserved antigenic B-cell epitopes 1227:1267 Three conserved antigenic B-cell epitopes were predicted in the E2 regions and also 11 short peptides were designed from the highly conserved residues. 25598792 0 35 theme 5a 33:34 arg1 proteins 45:52 HCV genotype 5a envelope proteins 20:52 HCV genotype 5a envelope proteins 20:52 Characterization of HCV genotype 5a envelope proteins: implications for vaccine development and therapeutic entry target. 25598792 5 36 theme HCV 1085:1087 arg1 5a 1098:1099 HCV genotype 5a 1085:1099 HCV genotype 5a 1085:1099 PATIENTS AND METHODS This study was conducted through PCR amplification of E1 and E2 regions, sequencing, prediction of B-cell epitopes, analysis of N-linked glycosylation and peptide design in 18 samples of HCV genotype 5a from South African. 25598792 1 37 with causes 177:182 arg1 estimation 234:243 an estimation 231:243 an estimation of 185 million people with infection 231:280 BACKGROUND Hepatitis C virus (HCV) is one of the major causes of cirrhosis and hepatocellular carcinoma with an estimation of 185 million people with infection. 25598792 2 38 theme emerging 431:438 arg1 variants 447:454 emerging escape variants 431:454 emerging escape variants 431:454 The E2 is the main target for neutralizing antibody responses and the variation of this region is related to maintenance of persistent infection by emerging escape variants and subsequent development of chronic infection. 25598792 8 39 theme able 1513:1516 arg1 inhibitors 1489:1498 entry inhibitors 1483:1498 entry inhibitors 1483:1498 CONCLUSIONS This study provided conserved B-cell epitopes and peptides that can be useful for designing entry inhibitors and vaccines able to cover a global population, especially where genotype 5a is common. 25598792 0 40 theme proteins 45:52 arg1 Characterization 0:15 Characterization 0:15 Characterization of HCV genotype 5a envelope proteins: implications for vaccine development and therapeutic entry target. 0:120 Characterization of HCV genotype 5a envelope proteins: implications for vaccine development and therapeutic entry target. 25598792 5 41 theme 5a 1098:1099 arg1 samples 1074:1080 18 samples 1071:1080 18 samples of HCV genotype 5a from South African 1071:1118 PATIENTS AND METHODS This study was conducted through PCR amplification of E1 and E2 regions, sequencing, prediction of B-cell epitopes, analysis of N-linked glycosylation and peptide design in 18 samples of HCV genotype 5a from South African. 25598792 2 42 theme main 297:300 arg1 target 302:307 the main target 293:307 the main target for neutralizing antibody responses 293:343 The E2 is the main target for neutralizing antibody responses and the variation of this region is related to maintenance of persistent infection by emerging escape variants and subsequent development of chronic infection. 25598792 2 42 theme main 297:300 arg1 E2 287:288 The E2 283:288 The E2 283:288 The E2 is the main target for neutralizing antibody responses and the variation of this region is related to maintenance of persistent infection by emerging escape variants and subsequent development of chronic infection. 25598792 5 43 theme E1 952:953 arg1 regions 962:968 E1 and E2 regions 952:968 E1 and E2 regions 952:968 PATIENTS AND METHODS This study was conducted through PCR amplification of E1 and E2 regions, sequencing, prediction of B-cell epitopes, analysis of N-linked glycosylation and peptide design in 18 samples of HCV genotype 5a from South African. 25598792 8 44 theme global 1529:1534 arg1 population 1536:1545 a global population 1527:1545 a global population 1527:1545 CONCLUSIONS This study provided conserved B-cell epitopes and peptides that can be useful for designing entry inhibitors and vaccines able to cover a global population, especially where genotype 5a is common. 25598792 4 45 theme B-cell 769:774 arg1 epitopes 776:783 conserved B-cell epitopes 759:783 conserved B-cell epitopes 759:783 OBJECTIVES The objective of this study was to characterize genotype 5a E1 and E2 sequences to determine possible glycosylation sites, conserved B-cell epitopes and peptides in HCV that could be useful targets in design of vaccine and entry inhibitors. 25598792 1 46 theme carcinoma 216:224 arg1 causes 177:182 the major causes 167:182 the major causes of cirrhosis and hepatocellular carcinoma with an estimation of 185 million people with infection 167:280 BACKGROUND Hepatitis C virus (HCV) is one of the major causes of cirrhosis and hepatocellular carcinoma with an estimation of 185 million people with infection. 25598792 5 47 theme E2 959:960 arg1 regions 962:968 E1 and E2 regions 952:968 E1 and E2 regions 952:968 PATIENTS AND METHODS This study was conducted through PCR amplification of E1 and E2 regions, sequencing, prediction of B-cell epitopes, analysis of N-linked glycosylation and peptide design in 18 samples of HCV genotype 5a from South African. 25598792 2 48 theme antibody 326:333 arg1 responses 335:343 antibody responses 326:343 antibody responses 326:343 The E2 is the main target for neutralizing antibody responses and the variation of this region is related to maintenance of persistent infection by emerging escape variants and subsequent development of chronic infection. 25598792 4 49 theme useful 819:824 arg1 targets 826:832 useful targets 819:832 useful targets 819:832 OBJECTIVES The objective of this study was to characterize genotype 5a E1 and E2 sequences to determine possible glycosylation sites, conserved B-cell epitopes and peptides in HCV that could be useful targets in design of vaccine and entry inhibitors. 25598792 8 50 dep CONCLUSIONS 1379:1389 arg1 provided 1402:1409 provided 1402:1409 provided conserved B-cell epitopes and peptides that can be useful for designing entry inhibitors and vaccines able to cover a global population, especially where genotype 5a is common 1402:1585 CONCLUSIONS This study provided conserved B-cell epitopes and peptides that can be useful for designing entry inhibitors and vaccines able to cover a global population, especially where genotype 5a is common. 25598792 4 51 gly glycosylation 738:750 arg2 sites 752:756 possible glycosylation sites 729:756 possible glycosylation sites 729:756 OBJECTIVES The objective of this study was to characterize genotype 5a E1 and E2 sequences to determine possible glycosylation sites, conserved B-cell epitopes and peptides in HCV that could be useful targets in design of vaccine and entry inhibitors. 25598792 6 52 theme E2 1187:1188 arg1 regions 1190:1196 E1 and E2 regions 1180:1196 E1 and E2 regions 1180:1196 RESULTS Differences in the probability of glycosylation in E1 and E2 regions were observed in this study. 25598792 1 53 theme major 171:175 arg1 causes 177:182 the major causes 167:182 the major causes of cirrhosis and hepatocellular carcinoma with an estimation of 185 million people with infection 167:280 BACKGROUND Hepatitis C virus (HCV) is one of the major causes of cirrhosis and hepatocellular carcinoma with an estimation of 185 million people with infection. 25598792 4 54 theme inhibitors 865:874 arg1 design 837:842 design 837:842 design of vaccine and entry inhibitors 837:874 OBJECTIVES The objective of this study was to characterize genotype 5a E1 and E2 sequences to determine possible glycosylation sites, conserved B-cell epitopes and peptides in HCV that could be useful targets in design of vaccine and entry inhibitors. 25598792 7 55 theme short 1314:1318 arg1 peptides 1320:1327 11 short peptides 1311:1327 11 short peptides 1311:1327 Three conserved antigenic B-cell epitopes were predicted in the E2 regions and also 11 short peptides were designed from the highly conserved residues. 25598792 5 56 theme N-linked 1026:1033 arg1 glycosylation 1035:1047 N-linked glycosylation 1026:1047 N-linked glycosylation 1026:1047 PATIENTS AND METHODS This study was conducted through PCR amplification of E1 and E2 regions, sequencing, prediction of B-cell epitopes, analysis of N-linked glycosylation and peptide design in 18 samples of HCV genotype 5a from South African. 25598792 4 57 from peptides 789:796 arg1 HCV 801:803 HCV 801:803 HCV 801:803 OBJECTIVES The objective of this study was to characterize genotype 5a E1 and E2 sequences to determine possible glycosylation sites, conserved B-cell epitopes and peptides in HCV that could be useful targets in design of vaccine and entry inhibitors. 25598792 8 58 theme conserved 1411:1419 arg1 epitopes 1428:1435 conserved B-cell epitopes 1411:1435 conserved B-cell epitopes 1411:1435 CONCLUSIONS This study provided conserved B-cell epitopes and peptides that can be useful for designing entry inhibitors and vaccines able to cover a global population, especially where genotype 5a is common. 25598792 4 59 from epitopes 776:783 arg1 HCV 801:803 HCV 801:803 HCV 801:803 OBJECTIVES The objective of this study was to characterize genotype 5a E1 and E2 sequences to determine possible glycosylation sites, conserved B-cell epitopes and peptides in HCV that could be useful targets in design of vaccine and entry inhibitors. 25598792 1 60 theme Hepatitis 133:141 arg1 HCV 152:154 HCV 152:154 HCV 152:154 BACKGROUND Hepatitis C virus (HCV) is one of the major causes of cirrhosis and hepatocellular carcinoma with an estimation of 185 million people with infection. 25598792 1 60 theme Hepatitis 133:141 arg1 virus 145:149 BACKGROUND Hepatitis C virus 122:149 BACKGROUND Hepatitis C virus (HCV) 122:155 BACKGROUND Hepatitis C virus (HCV) is one of the major causes of cirrhosis and hepatocellular carcinoma with an estimation of 185 million people with infection. 25598792 4 61 theme genotype 684:691 arg1 E1 696:697 genotype 5a E1 684:697 genotype 5a E1 684:697 OBJECTIVES The objective of this study was to characterize genotype 5a E1 and E2 sequences to determine possible glycosylation sites, conserved B-cell epitopes and peptides in HCV that could be useful targets in design of vaccine and entry inhibitors. 25598792 5 62 theme epitopes 1004:1011 arg1 analysis 1014:1021 analysis 1014:1021 analysis of N-linked glycosylation 1014:1047 PATIENTS AND METHODS This study was conducted through PCR amplification of E1 and E2 regions, sequencing, prediction of B-cell epitopes, analysis of N-linked glycosylation and peptide design in 18 samples of HCV genotype 5a from South African. 25598792 5 62 theme epitopes 1004:1011 arg1 prediction 983:992 prediction 983:992 prediction of B-cell epitopes 983:1011 PATIENTS AND METHODS This study was conducted through PCR amplification of E1 and E2 regions, sequencing, prediction of B-cell epitopes, analysis of N-linked glycosylation and peptide design in 18 samples of HCV genotype 5a from South African. 25598792 5 62 theme epitopes 1004:1011 arg1 design 1061:1066 peptide design 1053:1066 peptide design 1053:1066 PATIENTS AND METHODS This study was conducted through PCR amplification of E1 and E2 regions, sequencing, prediction of B-cell epitopes, analysis of N-linked glycosylation and peptide design in 18 samples of HCV genotype 5a from South African. 25598792 5 62 theme epitopes 1004:1011 arg1 sequencing 971:980 sequencing 971:980 sequencing 971:980 PATIENTS AND METHODS This study was conducted through PCR amplification of E1 and E2 regions, sequencing, prediction of B-cell epitopes, analysis of N-linked glycosylation and peptide design in 18 samples of HCV genotype 5a from South African. 25598792 5 62 theme epitopes 1004:1011 arg1 amplification 935:947 PCR amplification 931:947 PCR amplification of E1 and E2 regions 931:968 PATIENTS AND METHODS This study was conducted through PCR amplification of E1 and E2 regions, sequencing, prediction of B-cell epitopes, analysis of N-linked glycosylation and peptide design in 18 samples of HCV genotype 5a from South African. 25598792 2 63 theme development 471:481 arg1 maintenance 392:402 maintenance 392:402 maintenance of persistent infection by emerging escape variants and subsequent development of chronic infection 392:502 The E2 is the main target for neutralizing antibody responses and the variation of this region is related to maintenance of persistent infection by emerging escape variants and subsequent development of chronic infection. 25598792 4 64 from sites 752:756 arg1 HCV 801:803 HCV 801:803 HCV 801:803 OBJECTIVES The objective of this study was to characterize genotype 5a E1 and E2 sequences to determine possible glycosylation sites, conserved B-cell epitopes and peptides in HCV that could be useful targets in design of vaccine and entry inhibitors. 25598792 5 65 link N-linked 1026:1033 arg1 glycosylation 1035:1047 N-linked glycosylation 1026:1047 N-linked glycosylation 1026:1047 PATIENTS AND METHODS This study was conducted through PCR amplification of E1 and E2 regions, sequencing, prediction of B-cell epitopes, analysis of N-linked glycosylation and peptide design in 18 samples of HCV genotype 5a from South African. 25598792 4 66 theme study 658:662 arg1 objective 640:648 The objective 636:648 The objective of this study 636:662 OBJECTIVES The objective of this study was to characterize genotype 5a E1 and E2 sequences to determine possible glycosylation sites, conserved B-cell epitopes and peptides in HCV that could be useful targets in design of vaccine and entry inhibitors. 25598792 6 67 from probability 1148:1158 arg1 regions 1190:1196 E1 and E2 regions 1180:1196 E1 and E2 regions 1180:1196 RESULTS Differences in the probability of glycosylation in E1 and E2 regions were observed in this study. 25598792 0 68 theme therapeutic 96:106 arg1 target 114:119 therapeutic entry target 96:119 therapeutic entry target 96:119 Characterization of HCV genotype 5a envelope proteins: implications for vaccine development and therapeutic entry target. 25598792 5 69 theme PCR 931:933 arg1 amplification 935:947 PCR amplification 931:947 PCR amplification of E1 and E2 regions 931:968 PATIENTS AND METHODS This study was conducted through PCR amplification of E1 and E2 regions, sequencing, prediction of B-cell epitopes, analysis of N-linked glycosylation and peptide design in 18 samples of HCV genotype 5a from South African. 25598792 2 70 theme chronic 486:492 arg1 infection 494:502 chronic infection 486:502 chronic infection 486:502 The E2 is the main target for neutralizing antibody responses and the variation of this region is related to maintenance of persistent infection by emerging escape variants and subsequent development of chronic infection. 25598792 4 71 theme possible 729:736 arg1 sites 752:756 possible glycosylation sites 729:756 possible glycosylation sites 729:756 OBJECTIVES The objective of this study was to characterize genotype 5a E1 and E2 sequences to determine possible glycosylation sites, conserved B-cell epitopes and peptides in HCV that could be useful targets in design of vaccine and entry inhibitors. 25598792 7 72 theme B-cell 1253:1258 arg1 epitopes 1260:1267 Three conserved antigenic B-cell epitopes 1227:1267 Three conserved antigenic B-cell epitopes 1227:1267 Three conserved antigenic B-cell epitopes were predicted in the E2 regions and also 11 short peptides were designed from the highly conserved residues. 25598792 2 73 theme persistent 407:416 arg1 infection 418:426 persistent infection 407:426 persistent infection by emerging escape variants 407:454 The E2 is the main target for neutralizing antibody responses and the variation of this region is related to maintenance of persistent infection by emerging escape variants and subsequent development of chronic infection. 25598792 4 74 theme E1 696:697 arg1 sequences 706:714 genotype 5a E1 and E2 sequences 684:714 genotype 5a E1 and E2 sequences 684:714 OBJECTIVES The objective of this study was to characterize genotype 5a E1 and E2 sequences to determine possible glycosylation sites, conserved B-cell epitopes and peptides in HCV that could be useful targets in design of vaccine and entry inhibitors. 25598792 0 75 theme genotype 24:31 arg1 proteins 45:52 HCV genotype 5a envelope proteins 20:52 HCV genotype 5a envelope proteins 20:52 Characterization of HCV genotype 5a envelope proteins: implications for vaccine development and therapeutic entry target. 25598792 1 76 theme people 260:265 arg1 estimation 234:243 an estimation 231:243 an estimation of 185 million people with infection 231:280 BACKGROUND Hepatitis C virus (HCV) is one of the major causes of cirrhosis and hepatocellular carcinoma with an estimation of 185 million people with infection. 25598792 7 77 theme conserved 1233:1241 arg1 epitopes 1260:1267 Three conserved antigenic B-cell epitopes 1227:1267 Three conserved antigenic B-cell epitopes 1227:1267 Three conserved antigenic B-cell epitopes were predicted in the E2 regions and also 11 short peptides were designed from the highly conserved residues. 25598792 4 78 theme E2 703:704 arg1 sequences 706:714 genotype 5a E1 and E2 sequences 684:714 genotype 5a E1 and E2 sequences 684:714 OBJECTIVES The objective of this study was to characterize genotype 5a E1 and E2 sequences to determine possible glycosylation sites, conserved B-cell epitopes and peptides in HCV that could be useful targets in design of vaccine and entry inhibitors. 25598792 0 79 theme envelope 36:43 arg1 proteins 45:52 HCV genotype 5a envelope proteins 20:52 HCV genotype 5a envelope proteins 20:52 Characterization of HCV genotype 5a envelope proteins: implications for vaccine development and therapeutic entry target. 25598792 5 80 theme regions 962:968 arg1 analysis 1014:1021 analysis 1014:1021 analysis of N-linked glycosylation 1014:1047 PATIENTS AND METHODS This study was conducted through PCR amplification of E1 and E2 regions, sequencing, prediction of B-cell epitopes, analysis of N-linked glycosylation and peptide design in 18 samples of HCV genotype 5a from South African. 25598792 5 80 theme regions 962:968 arg1 prediction 983:992 prediction 983:992 prediction of B-cell epitopes 983:1011 PATIENTS AND METHODS This study was conducted through PCR amplification of E1 and E2 regions, sequencing, prediction of B-cell epitopes, analysis of N-linked glycosylation and peptide design in 18 samples of HCV genotype 5a from South African. 25598792 5 80 theme regions 962:968 arg1 design 1061:1066 peptide design 1053:1066 peptide design 1053:1066 PATIENTS AND METHODS This study was conducted through PCR amplification of E1 and E2 regions, sequencing, prediction of B-cell epitopes, analysis of N-linked glycosylation and peptide design in 18 samples of HCV genotype 5a from South African. 25598792 5 80 theme regions 962:968 arg1 sequencing 971:980 sequencing 971:980 sequencing 971:980 PATIENTS AND METHODS This study was conducted through PCR amplification of E1 and E2 regions, sequencing, prediction of B-cell epitopes, analysis of N-linked glycosylation and peptide design in 18 samples of HCV genotype 5a from South African. 25598792 5 80 theme regions 962:968 arg1 amplification 935:947 PCR amplification 931:947 PCR amplification of E1 and E2 regions 931:968 PATIENTS AND METHODS This study was conducted through PCR amplification of E1 and E2 regions, sequencing, prediction of B-cell epitopes, analysis of N-linked glycosylation and peptide design in 18 samples of HCV genotype 5a from South African. 25598792 2 81 theme escape 440:445 arg1 variants 447:454 emerging escape variants 431:454 emerging escape variants 431:454 The E2 is the main target for neutralizing antibody responses and the variation of this region is related to maintenance of persistent infection by emerging escape variants and subsequent development of chronic infection. 25598792 3 82 theme therapeutic 593:603 arg1 drugs 605:609 therapeutic drugs 593:609 therapeutic drugs 593:609 While both E1 and E2 are hypervariable in nature, it is difficult to design vaccines or therapeutic drugs against them. 25598792 2 83 theme region 371:376 arg1 related 381:387 related 381:387 related 381:387 The E2 is the main target for neutralizing antibody responses and the variation of this region is related to maintenance of persistent infection by emerging escape variants and subsequent development of chronic infection. 25598792 2 83 theme region 371:376 arg1 variation 353:361 the variation 349:361 the variation of this region 349:376 The E2 is the main target for neutralizing antibody responses and the variation of this region is related to maintenance of persistent infection by emerging escape variants and subsequent development of chronic infection. 25598792 5 84 theme genotype 1089:1096 arg1 5a 1098:1099 HCV genotype 5a 1085:1099 HCV genotype 5a 1085:1099 PATIENTS AND METHODS This study was conducted through PCR amplification of E1 and E2 regions, sequencing, prediction of B-cell epitopes, analysis of N-linked glycosylation and peptide design in 18 samples of HCV genotype 5a from South African. 25598792 0 85 dep Characterization 0:15 arg1 implications 55:66 implications 55:66 Characterization of HCV genotype 5a envelope proteins: implications for vaccine development and therapeutic entry target. 0:120 Characterization of HCV genotype 5a envelope proteins: implications for vaccine development and therapeutic entry target. 25598792 5 86 from South 1106:1110 arg1 samples 1074:1080 18 samples 1071:1080 18 samples of HCV genotype 5a from South African 1071:1118 PATIENTS AND METHODS This study was conducted through PCR amplification of E1 and E2 regions, sequencing, prediction of B-cell epitopes, analysis of N-linked glycosylation and peptide design in 18 samples of HCV genotype 5a from South African. 25598792 1 87 theme hepatocellular 201:214 arg1 carcinoma 216:224 hepatocellular carcinoma 201:224 hepatocellular carcinoma 201:224 BACKGROUND Hepatitis C virus (HCV) is one of the major causes of cirrhosis and hepatocellular carcinoma with an estimation of 185 million people with infection. 25598792 4 88 dep OBJECTIVES 625:634 arg1 was 664:666 was 664:666 was to characterize genotype 5a E1 and E2 sequences to determine possible glycosylation sites, conserved B-cell epitopes and peptides in HCV that could be useful targets in design of vaccine and entry inhibitors 664:874 OBJECTIVES The objective of this study was to characterize genotype 5a E1 and E2 sequences to determine possible glycosylation sites, conserved B-cell epitopes and peptides in HCV that could be useful targets in design of vaccine and entry inhibitors. 25598792 4 89 theme conserved 759:767 arg1 epitopes 776:783 conserved B-cell epitopes 759:783 conserved B-cell epitopes 759:783 OBJECTIVES The objective of this study was to characterize genotype 5a E1 and E2 sequences to determine possible glycosylation sites, conserved B-cell epitopes and peptides in HCV that could be useful targets in design of vaccine and entry inhibitors. 24818024 5 0 theme 38 kDa 632:637 arg1 polypeptide 651:661 The 38 kDa RCA binding polypeptide 628:661 The 38 kDa RCA binding polypeptide of cauda sperm PM 628:679 The 38 kDa RCA binding polypeptide of cauda sperm PM was purified and exhibited a charge train of three distinct spots with isoelectric points (pH 5.3 and 5.8). 24818024 10 1 theme bovine 1393:1398 arg1 membranes 1424:1432 bovine epididymal sperm plasma membranes 1393:1432 bovine epididymal sperm plasma membranes 1393:1432 Our biochemical results provide evidence on the presence of TEX101 in bovine epididymal sperm plasma membranes and may have a potential role in sperm-egg interaction. 24818024 8 2 theme sperm 1129:1133 arg1 membrane 1135:1142 sperm membrane 1129:1142 sperm membrane 1129:1142 The native TEX101 polypeptide contains ~17 kDa N-linked oligosaccharides and the polypeptide is anchored to sperm membrane via a glycosylphosphatidylinositol lipid linkage. 24818024 6 3 theme Testis 864:869 arg1 TEX101 894:899 TEX101 894:899 TEX101 894:899 Proteomic identification yielded ten peptides that matched the sequence of Testis Expressed 101 protein (TEX101). 24818024 6 3 theme Testis 864:869 arg1 protein 885:891 Testis Expressed 101 protein 864:891 Testis Expressed 101 protein (TEX101) 864:900 Proteomic identification yielded ten peptides that matched the sequence of Testis Expressed 101 protein (TEX101). 24818024 5 4 theme binding 643:649 arg1 polypeptide 651:661 The 38 kDa RCA binding polypeptide 628:661 The 38 kDa RCA binding polypeptide of cauda sperm PM 628:679 The 38 kDa RCA binding polypeptide of cauda sperm PM was purified and exhibited a charge train of three distinct spots with isoelectric points (pH 5.3 and 5.8). 24818024 10 5 theme TEX101 1383:1388 arg1 presence 1371:1378 the presence 1367:1378 the presence of TEX101 in bovine epididymal sperm plasma membranes 1367:1432 Our biochemical results provide evidence on the presence of TEX101 in bovine epididymal sperm plasma membranes and may have a potential role in sperm-egg interaction. 24818024 9 6 located localized 1285:1293 arg2 polypeptide 1270:1280 the polypeptide 1266:1280 the polypeptide 1266:1280 Immunofluorescence staining of sperm with anti-TEX101 demonstrated that the polypeptide is localized at the head of cauda sperm. 24818024 9 6 located localized 1285:1293 arg1 head 1302:1305 the head 1298:1305 the head of cauda sperm 1298:1320 Immunofluorescence staining of sperm with anti-TEX101 demonstrated that the polypeptide is localized at the head of cauda sperm. 24818024 8 7 theme glycosylphosphatidylinositol 1150:1177 arg1 linkage 1185:1191 a glycosylphosphatidylinositol lipid linkage 1148:1191 a glycosylphosphatidylinositol lipid linkage 1148:1191 The native TEX101 polypeptide contains ~17 kDa N-linked oligosaccharides and the polypeptide is anchored to sperm membrane via a glycosylphosphatidylinositol lipid linkage. 24818024 10 8 theme sperm 1411:1415 arg1 membranes 1424:1432 bovine epididymal sperm plasma membranes 1393:1432 bovine epididymal sperm plasma membranes 1393:1432 Our biochemical results provide evidence on the presence of TEX101 in bovine epididymal sperm plasma membranes and may have a potential role in sperm-egg interaction. 24818024 4 9 theme binding 606:612 arg1 polypeptides 614:625 the several major RCA binding polypeptides 584:625 the several major RCA binding polypeptides 584:625 Lectin blots of caput and cauda sperm PM revealed a 38 kDa polypeptide exhibiting the highest affinity to RCA among the several major RCA binding polypeptides. 24818024 9 10 theme sperm 1225:1229 arg1 staining 1213:1220 Immunofluorescence staining 1194:1220 Immunofluorescence staining of sperm with anti-TEX101 1194:1246 Immunofluorescence staining of sperm with anti-TEX101 demonstrated that the polypeptide is localized at the head of cauda sperm. 24818024 8 11 link N-linked 1068:1075 arg1 oligosaccharides 1077:1092 ~17 kDa N-linked oligosaccharides 1060:1092 ~17 kDa N-linked oligosaccharides 1060:1092 The native TEX101 polypeptide contains ~17 kDa N-linked oligosaccharides and the polypeptide is anchored to sperm membrane via a glycosylphosphatidylinositol lipid linkage. 24818024 7 12 from fractions 1010:1018 arg1 present 959:965 present 959:965 present 959:965 Western blots data revealed that bovine sperm TEX101 is present in both testicular and epididymal sperm PM fractions. 24818024 5 13 theme cauda 666:670 arg1 sperm 672:676 cauda sperm 666:676 cauda sperm PM 666:679 The 38 kDa RCA binding polypeptide of cauda sperm PM was purified and exhibited a charge train of three distinct spots with isoelectric points (pH 5.3 and 5.8). 24818024 7 14 theme sperm 1001:1005 arg1 fractions 1010:1018 both testicular and epididymal sperm PM fractions 970:1018 both testicular and epididymal sperm PM fractions 970:1018 Western blots data revealed that bovine sperm TEX101 is present in both testicular and epididymal sperm PM fractions. 24818024 2 15 theme molecular 214:222 arg1 characterization 224:239 the molecular characterization 210:239 the molecular characterization of RCA binding glycocalyx in sperm membranes 210:284 However, the molecular characterization of RCA binding glycocalyx in sperm membranes and its mechanism of action are poorly understood. 24818024 1 16 theme Communis 128:135 arg1 Agglutinin 137:146 Ricinus Communis Agglutinin I 120:148 Ricinus Communis Agglutinin I (RCA) binding glycocalyx 120:173 Several studies exhibit the presence of Ricinus Communis Agglutinin I (RCA) binding glycocalyx in mammalian spermatozoa. 24818024 1 16 theme Communis 128:135 arg1 RCA 151:153 RCA 151:153 RCA 151:153 Several studies exhibit the presence of Ricinus Communis Agglutinin I (RCA) binding glycocalyx in mammalian spermatozoa. 24818024 7 17 dep blots 911:915 arg1 data 917:920 data 917:920 Western blots data 903:920 Western blots data revealed that bovine sperm TEX101 is present in both testicular and epididymal sperm PM fractions. 24818024 5 18 theme sperm 672:676 arg1 PM 678:679 cauda sperm PM 666:679 cauda sperm PM 666:679 The 38 kDa RCA binding polypeptide of cauda sperm PM was purified and exhibited a charge train of three distinct spots with isoelectric points (pH 5.3 and 5.8). 24818024 7 19 theme sperm 943:947 arg1 TEX101 949:954 bovine sperm TEX101 936:954 bovine sperm TEX101 936:954 Western blots data revealed that bovine sperm TEX101 is present in both testicular and epididymal sperm PM fractions. 24818024 2 20 from mechanism 294:302 arg1 membranes 276:284 sperm membranes 270:284 sperm membranes 270:284 However, the molecular characterization of RCA binding glycocalyx in sperm membranes and its mechanism of action are poorly understood. 24818024 2 21 theme binding 248:254 arg1 glycocalyx 256:265 RCA binding glycocalyx 244:265 RCA binding glycocalyx in sperm membranes 244:284 However, the molecular characterization of RCA binding glycocalyx in sperm membranes and its mechanism of action are poorly understood. 24818024 0 22 from Characterization 19:34 arg1 Spermatozoa 67:77 Bovine Epididymal Spermatozoa 49:77 Bovine Epididymal Spermatozoa 49:77 Identification and Characterization of TEX101 in Bovine Epididymal Spermatozoa. 24818024 5 23 theme spots 741:745 arg1 train 717:721 a charge train 708:721 a charge train of three distinct spots 708:745 The 38 kDa RCA binding polypeptide of cauda sperm PM was purified and exhibited a charge train of three distinct spots with isoelectric points (pH 5.3 and 5.8). 24818024 1 24 theme binding 156:162 arg1 glycocalyx 164:173 Ricinus Communis Agglutinin I (RCA) binding glycocalyx 120:173 Ricinus Communis Agglutinin I (RCA) binding glycocalyx 120:173 Several studies exhibit the presence of Ricinus Communis Agglutinin I (RCA) binding glycocalyx in mammalian spermatozoa. 24818024 3 25 theme study 358:362 arg1 objective 341:349 The objective 337:349 The objective of the study 337:362 The objective of the study was to identify and to characterize RCA binding glycoprotein of the bovine sperm plasma membranes (PM). 24818024 0 26 from Identification 0:13 arg1 Spermatozoa 67:77 Bovine Epididymal Spermatozoa 49:77 Bovine Epididymal Spermatozoa 49:77 Identification and Characterization of TEX101 in Bovine Epididymal Spermatozoa. 24818024 7 27 theme Western 903:909 arg1 blots 911:915 Western blots data 903:920 Western blots data 903:920 Western blots data revealed that bovine sperm TEX101 is present in both testicular and epididymal sperm PM fractions. 24818024 2 28 from characterization 224:239 arg1 membranes 276:284 sperm membranes 270:284 sperm membranes 270:284 However, the molecular characterization of RCA binding glycocalyx in sperm membranes and its mechanism of action are poorly understood. 24818024 7 29 attach present 959:965 arg1 fractions 1010:1018 both testicular and epididymal sperm PM fractions 970:1018 both testicular and epididymal sperm PM fractions 970:1018 Western blots data revealed that bovine sperm TEX101 is present in both testicular and epididymal sperm PM fractions. 24818024 7 29 attach present 959:965 arg2 TEX101 949:954 bovine sperm TEX101 936:954 bovine sperm TEX101 936:954 Western blots data revealed that bovine sperm TEX101 is present in both testicular and epididymal sperm PM fractions. 24818024 10 30 theme sperm-egg 1467:1475 arg1 interaction 1477:1487 sperm-egg interaction 1467:1487 sperm-egg interaction 1467:1487 Our biochemical results provide evidence on the presence of TEX101 in bovine epididymal sperm plasma membranes and may have a potential role in sperm-egg interaction. 24818024 3 31 theme bovine 432:437 arg1 membranes 452:460 the bovine sperm plasma membranes 428:460 the bovine sperm plasma membranes (PM) 428:465 The objective of the study was to identify and to characterize RCA binding glycoprotein of the bovine sperm plasma membranes (PM). 24818024 3 31 theme bovine 432:437 arg1 PM 463:464 PM 463:464 PM 463:464 The objective of the study was to identify and to characterize RCA binding glycoprotein of the bovine sperm plasma membranes (PM). 24818024 9 32 theme sperm 1316:1320 arg1 head 1302:1305 the head 1298:1305 the head of cauda sperm 1298:1320 Immunofluorescence staining of sperm with anti-TEX101 demonstrated that the polypeptide is localized at the head of cauda sperm. 24818024 4 33 theme Lectin 468:473 arg1 blots 475:479 Lectin blots 468:479 Lectin blots of caput and cauda sperm PM 468:507 Lectin blots of caput and cauda sperm PM revealed a 38 kDa polypeptide exhibiting the highest affinity to RCA among the several major RCA binding polypeptides. 24818024 9 34 with staining 1213:1220 arg1 anti-TEX101 1236:1246 anti-TEX101 1236:1246 anti-TEX101 1236:1246 Immunofluorescence staining of sperm with anti-TEX101 demonstrated that the polypeptide is localized at the head of cauda sperm. 24818024 2 35 from glycocalyx 256:265 arg1 membranes 276:284 sperm membranes 270:284 sperm membranes 270:284 However, the molecular characterization of RCA binding glycocalyx in sperm membranes and its mechanism of action are poorly understood. 24818024 4 36 theme 38 kDa 520:525 arg1 polypeptide 527:537 a 38 kDa polypeptide 518:537 a 38 kDa polypeptide exhibiting the highest affinity to RCA among the several major RCA binding polypeptides 518:625 Lectin blots of caput and cauda sperm PM revealed a 38 kDa polypeptide exhibiting the highest affinity to RCA among the several major RCA binding polypeptides. 24818024 8 37 theme native 1025:1030 arg1 polypeptide 1039:1049 The native TEX101 polypeptide 1021:1049 The native TEX101 polypeptide 1021:1049 The native TEX101 polypeptide contains ~17 kDa N-linked oligosaccharides and the polypeptide is anchored to sperm membrane via a glycosylphosphatidylinositol lipid linkage. 24818024 10 38 from evidence 1355:1362 arg1 presence 1371:1378 the presence 1367:1378 the presence of TEX101 in bovine epididymal sperm plasma membranes 1367:1432 Our biochemical results provide evidence on the presence of TEX101 in bovine epididymal sperm plasma membranes and may have a potential role in sperm-egg interaction. 24818024 3 39 theme binding 404:410 arg1 glycoprotein 412:423 RCA binding glycoprotein 400:423 RCA binding glycoprotein of the bovine sperm plasma membranes (PM) 400:465 The objective of the study was to identify and to characterize RCA binding glycoprotein of the bovine sperm plasma membranes (PM). 24818024 3 40 theme plasma 445:450 arg1 membranes 452:460 the bovine sperm plasma membranes 428:460 the bovine sperm plasma membranes (PM) 428:465 The objective of the study was to identify and to characterize RCA binding glycoprotein of the bovine sperm plasma membranes (PM). 24818024 3 40 theme plasma 445:450 arg1 PM 463:464 PM 463:464 PM 463:464 The objective of the study was to identify and to characterize RCA binding glycoprotein of the bovine sperm plasma membranes (PM). 24818024 0 41 theme TEX101 39:44 arg1 Characterization 19:34 Characterization 19:34 Characterization 19:34 Identification and Characterization of TEX101 in Bovine Epididymal Spermatozoa. 24818024 0 41 theme TEX101 39:44 arg1 Identification 0:13 Identification 0:13 Identification 0:13 Identification and Characterization of TEX101 in Bovine Epididymal Spermatozoa. 24818024 5 42 theme isoelectric 752:762 arg1 points 764:769 isoelectric points 752:769 isoelectric points (pH 5.3 and 5.8) 752:786 The 38 kDa RCA binding polypeptide of cauda sperm PM was purified and exhibited a charge train of three distinct spots with isoelectric points (pH 5.3 and 5.8). 24818024 5 42 theme isoelectric 752:762 arg1 pH 772:773 pH 5.3 and 5.8 772:785 pH 772:773 The 38 kDa RCA binding polypeptide of cauda sperm PM was purified and exhibited a charge train of three distinct spots with isoelectric points (pH 5.3 and 5.8). 24818024 5 42 theme isoelectric 752:762 arg1 5.8 783:785 5.8 783:785 5.8 783:785 The 38 kDa RCA binding polypeptide of cauda sperm PM was purified and exhibited a charge train of three distinct spots with isoelectric points (pH 5.3 and 5.8). 24818024 4 43 theme sperm 500:504 arg1 PM 506:507 caput and cauda sperm PM 484:507 caput and cauda sperm PM 484:507 Lectin blots of caput and cauda sperm PM revealed a 38 kDa polypeptide exhibiting the highest affinity to RCA among the several major RCA binding polypeptides. 24818024 0 44 theme Bovine 49:54 arg1 Spermatozoa 67:77 Bovine Epididymal Spermatozoa 49:77 Bovine Epididymal Spermatozoa 49:77 Identification and Characterization of TEX101 in Bovine Epididymal Spermatozoa. 24818024 8 45 theme ~17 kDa 1060:1066 arg1 oligosaccharides 1077:1092 ~17 kDa N-linked oligosaccharides 1060:1092 ~17 kDa N-linked oligosaccharides 1060:1092 The native TEX101 polypeptide contains ~17 kDa N-linked oligosaccharides and the polypeptide is anchored to sperm membrane via a glycosylphosphatidylinositol lipid linkage. 24818024 6 46 theme protein 885:891 arg1 sequence 852:859 the sequence 848:859 the sequence of Testis Expressed 101 protein (TEX101) 848:900 Proteomic identification yielded ten peptides that matched the sequence of Testis Expressed 101 protein (TEX101). 24818024 4 47 theme several 588:594 arg1 polypeptides 614:625 the several major RCA binding polypeptides 584:625 the several major RCA binding polypeptides 584:625 Lectin blots of caput and cauda sperm PM revealed a 38 kDa polypeptide exhibiting the highest affinity to RCA among the several major RCA binding polypeptides. 24818024 6 48 theme Expressed 871:879 arg1 TEX101 894:899 TEX101 894:899 TEX101 894:899 Proteomic identification yielded ten peptides that matched the sequence of Testis Expressed 101 protein (TEX101). 24818024 6 48 theme Expressed 871:879 arg1 protein 885:891 Testis Expressed 101 protein 864:891 Testis Expressed 101 protein (TEX101) 864:900 Proteomic identification yielded ten peptides that matched the sequence of Testis Expressed 101 protein (TEX101). 24818024 4 49 theme highest 554:560 arg1 affinity 562:569 the highest affinity 550:569 the highest affinity 550:569 Lectin blots of caput and cauda sperm PM revealed a 38 kDa polypeptide exhibiting the highest affinity to RCA among the several major RCA binding polypeptides. 24818024 10 50 theme plasma 1417:1422 arg1 membranes 1424:1432 bovine epididymal sperm plasma membranes 1393:1432 bovine epididymal sperm plasma membranes 1393:1432 Our biochemical results provide evidence on the presence of TEX101 in bovine epididymal sperm plasma membranes and may have a potential role in sperm-egg interaction. 24818024 5 51 theme RCA 639:641 arg1 polypeptide 651:661 The 38 kDa RCA binding polypeptide 628:661 The 38 kDa RCA binding polypeptide of cauda sperm PM 628:679 The 38 kDa RCA binding polypeptide of cauda sperm PM was purified and exhibited a charge train of three distinct spots with isoelectric points (pH 5.3 and 5.8). 24818024 7 52 located present 959:965 arg1 fractions 1010:1018 both testicular and epididymal sperm PM fractions 970:1018 both testicular and epididymal sperm PM fractions 970:1018 Western blots data revealed that bovine sperm TEX101 is present in both testicular and epididymal sperm PM fractions. 24818024 7 52 located present 959:965 arg2 TEX101 949:954 bovine sperm TEX101 936:954 bovine sperm TEX101 936:954 Western blots data revealed that bovine sperm TEX101 is present in both testicular and epididymal sperm PM fractions. 24818024 1 53 theme mammalian 178:186 arg1 spermatozoa 188:198 mammalian spermatozoa 178:198 mammalian spermatozoa 178:198 Several studies exhibit the presence of Ricinus Communis Agglutinin I (RCA) binding glycocalyx in mammalian spermatozoa. 24818024 1 54 theme glycocalyx 164:173 arg1 presence 108:115 the presence 104:115 the presence of Ricinus Communis Agglutinin I (RCA) binding glycocalyx in mammalian spermatozoa 104:198 Several studies exhibit the presence of Ricinus Communis Agglutinin I (RCA) binding glycocalyx in mammalian spermatozoa. 24818024 9 55 theme Immunofluorescence 1194:1211 arg1 staining 1213:1220 Immunofluorescence staining 1194:1220 Immunofluorescence staining of sperm with anti-TEX101 1194:1246 Immunofluorescence staining of sperm with anti-TEX101 demonstrated that the polypeptide is localized at the head of cauda sperm. 24818024 10 56 contain have 1442:1445 arg1 results 1339:1345 Our biochemical results 1323:1345 Our biochemical results 1323:1345 Our biochemical results provide evidence on the presence of TEX101 in bovine epididymal sperm plasma membranes and may have a potential role in sperm-egg interaction. 24818024 10 56 contain have 1442:1445 arg2 role 1459:1462 a potential role 1447:1462 a potential role 1447:1462 Our biochemical results provide evidence on the presence of TEX101 in bovine epididymal sperm plasma membranes and may have a potential role in sperm-egg interaction. 24818024 10 57 attach presence 1371:1378 arg2 TEX101 1383:1388 TEX101 1383:1388 TEX101 1383:1388 Our biochemical results provide evidence on the presence of TEX101 in bovine epididymal sperm plasma membranes and may have a potential role in sperm-egg interaction. 24818024 10 57 attach presence 1371:1378 arg1 membranes 1424:1432 bovine epididymal sperm plasma membranes 1393:1432 bovine epididymal sperm plasma membranes 1393:1432 Our biochemical results provide evidence on the presence of TEX101 in bovine epididymal sperm plasma membranes and may have a potential role in sperm-egg interaction. 24818024 5 58 theme PM 678:679 arg1 polypeptide 651:661 The 38 kDa RCA binding polypeptide 628:661 The 38 kDa RCA binding polypeptide of cauda sperm PM 628:679 The 38 kDa RCA binding polypeptide of cauda sperm PM was purified and exhibited a charge train of three distinct spots with isoelectric points (pH 5.3 and 5.8). 24818024 10 59 theme epididymal 1400:1409 arg1 membranes 1424:1432 bovine epididymal sperm plasma membranes 1393:1432 bovine epididymal sperm plasma membranes 1393:1432 Our biochemical results provide evidence on the presence of TEX101 in bovine epididymal sperm plasma membranes and may have a potential role in sperm-egg interaction. 24818024 2 60 theme action 307:312 arg1 mechanism 294:302 its mechanism 290:302 its mechanism of action 290:312 However, the molecular characterization of RCA binding glycocalyx in sperm membranes and its mechanism of action are poorly understood. 24818024 2 60 theme action 307:312 arg1 characterization 224:239 the molecular characterization 210:239 the molecular characterization of RCA binding glycocalyx in sperm membranes 210:284 However, the molecular characterization of RCA binding glycocalyx in sperm membranes and its mechanism of action are poorly understood. 24818024 8 61 theme lipid 1179:1183 arg1 linkage 1185:1191 a glycosylphosphatidylinositol lipid linkage 1148:1191 a glycosylphosphatidylinositol lipid linkage 1148:1191 The native TEX101 polypeptide contains ~17 kDa N-linked oligosaccharides and the polypeptide is anchored to sperm membrane via a glycosylphosphatidylinositol lipid linkage. 24818024 7 62 from present 959:965 arg1 fractions 1010:1018 both testicular and epididymal sperm PM fractions 970:1018 both testicular and epididymal sperm PM fractions 970:1018 Western blots data revealed that bovine sperm TEX101 is present in both testicular and epididymal sperm PM fractions. 24818024 7 63 theme PM 1007:1008 arg1 fractions 1010:1018 both testicular and epididymal sperm PM fractions 970:1018 both testicular and epididymal sperm PM fractions 970:1018 Western blots data revealed that bovine sperm TEX101 is present in both testicular and epididymal sperm PM fractions. 24818024 2 64 theme RCA 244:246 arg1 glycocalyx 256:265 RCA binding glycocalyx 244:265 RCA binding glycocalyx in sperm membranes 244:284 However, the molecular characterization of RCA binding glycocalyx in sperm membranes and its mechanism of action are poorly understood. 24818024 7 65 theme epididymal 990:999 arg1 fractions 1010:1018 both testicular and epididymal sperm PM fractions 970:1018 both testicular and epididymal sperm PM fractions 970:1018 Western blots data revealed that bovine sperm TEX101 is present in both testicular and epididymal sperm PM fractions. 24818024 1 66 theme Ricinus 120:126 arg1 Agglutinin 137:146 Ricinus Communis Agglutinin I 120:148 Ricinus Communis Agglutinin I (RCA) binding glycocalyx 120:173 Several studies exhibit the presence of Ricinus Communis Agglutinin I (RCA) binding glycocalyx in mammalian spermatozoa. 24818024 1 66 theme Ricinus 120:126 arg1 RCA 151:153 RCA 151:153 RCA 151:153 Several studies exhibit the presence of Ricinus Communis Agglutinin I (RCA) binding glycocalyx in mammalian spermatozoa. 24818024 1 67 attach presence 108:115 arg2 glycocalyx 164:173 Ricinus Communis Agglutinin I (RCA) binding glycocalyx 120:173 Ricinus Communis Agglutinin I (RCA) binding glycocalyx 120:173 Several studies exhibit the presence of Ricinus Communis Agglutinin I (RCA) binding glycocalyx in mammalian spermatozoa. 24818024 1 67 attach presence 108:115 arg1 spermatozoa 188:198 mammalian spermatozoa 178:198 mammalian spermatozoa 178:198 Several studies exhibit the presence of Ricinus Communis Agglutinin I (RCA) binding glycocalyx in mammalian spermatozoa. 24818024 7 68 theme testicular 975:984 arg1 fractions 1010:1018 both testicular and epididymal sperm PM fractions 970:1018 both testicular and epididymal sperm PM fractions 970:1018 Western blots data revealed that bovine sperm TEX101 is present in both testicular and epididymal sperm PM fractions. 24818024 2 69 theme sperm 270:274 arg1 membranes 276:284 sperm membranes 270:284 sperm membranes 270:284 However, the molecular characterization of RCA binding glycocalyx in sperm membranes and its mechanism of action are poorly understood. 24818024 1 70 theme Agglutinin 137:146 arg1 glycocalyx 164:173 Ricinus Communis Agglutinin I (RCA) binding glycocalyx 120:173 Ricinus Communis Agglutinin I (RCA) binding glycocalyx 120:173 Several studies exhibit the presence of Ricinus Communis Agglutinin I (RCA) binding glycocalyx in mammalian spermatozoa. 24818024 2 71 from membranes 276:284 arg1 mechanism 294:302 its mechanism 290:302 its mechanism of action 290:312 However, the molecular characterization of RCA binding glycocalyx in sperm membranes and its mechanism of action are poorly understood. 24818024 2 71 from membranes 276:284 arg1 characterization 224:239 the molecular characterization 210:239 the molecular characterization of RCA binding glycocalyx in sperm membranes 210:284 However, the molecular characterization of RCA binding glycocalyx in sperm membranes and its mechanism of action are poorly understood. 24818024 2 72 theme glycocalyx 256:265 arg1 mechanism 294:302 its mechanism 290:302 its mechanism of action 290:312 However, the molecular characterization of RCA binding glycocalyx in sperm membranes and its mechanism of action are poorly understood. 24818024 2 72 theme glycocalyx 256:265 arg1 characterization 224:239 the molecular characterization 210:239 the molecular characterization of RCA binding glycocalyx in sperm membranes 210:284 However, the molecular characterization of RCA binding glycocalyx in sperm membranes and its mechanism of action are poorly understood. 24818024 4 73 theme caput 484:488 arg1 PM 506:507 caput and cauda sperm PM 484:507 caput and cauda sperm PM 484:507 Lectin blots of caput and cauda sperm PM revealed a 38 kDa polypeptide exhibiting the highest affinity to RCA among the several major RCA binding polypeptides. 24818024 5 74 theme distinct 732:739 arg1 spots 741:745 three distinct spots 726:745 three distinct spots 726:745 The 38 kDa RCA binding polypeptide of cauda sperm PM was purified and exhibited a charge train of three distinct spots with isoelectric points (pH 5.3 and 5.8). 24818024 3 75 gly glycoprotein 412:423 arg1 glycoprotein 412:423 RCA binding glycoprotein 400:423 RCA binding glycoprotein of the bovine sperm plasma membranes (PM) 400:465 The objective of the study was to identify and to characterize RCA binding glycoprotein of the bovine sperm plasma membranes (PM). 24818024 7 76 theme bovine 936:941 arg1 TEX101 949:954 bovine sperm TEX101 936:954 bovine sperm TEX101 936:954 Western blots data revealed that bovine sperm TEX101 is present in both testicular and epididymal sperm PM fractions. 24818024 4 77 theme cauda 494:498 arg1 PM 506:507 caput and cauda sperm PM 484:507 caput and cauda sperm PM 484:507 Lectin blots of caput and cauda sperm PM revealed a 38 kDa polypeptide exhibiting the highest affinity to RCA among the several major RCA binding polypeptides. 24818024 5 78 theme charge 710:715 arg1 train 717:721 a charge train 708:721 a charge train of three distinct spots 708:745 The 38 kDa RCA binding polypeptide of cauda sperm PM was purified and exhibited a charge train of three distinct spots with isoelectric points (pH 5.3 and 5.8). 24818024 9 79 theme cauda 1310:1314 arg1 sperm 1316:1320 cauda sperm 1310:1320 cauda sperm 1310:1320 Immunofluorescence staining of sperm with anti-TEX101 demonstrated that the polypeptide is localized at the head of cauda sperm. 24818024 4 80 theme RCA 602:604 arg1 polypeptides 614:625 the several major RCA binding polypeptides 584:625 the several major RCA binding polypeptides 584:625 Lectin blots of caput and cauda sperm PM revealed a 38 kDa polypeptide exhibiting the highest affinity to RCA among the several major RCA binding polypeptides. 24818024 1 81 theme Several 80:86 arg1 studies 88:94 Several studies 80:94 Several studies 80:94 Several studies exhibit the presence of Ricinus Communis Agglutinin I (RCA) binding glycocalyx in mammalian spermatozoa. 24818024 3 82 theme sperm 439:443 arg1 membranes 452:460 the bovine sperm plasma membranes 428:460 the bovine sperm plasma membranes (PM) 428:465 The objective of the study was to identify and to characterize RCA binding glycoprotein of the bovine sperm plasma membranes (PM). 24818024 3 82 theme sperm 439:443 arg1 PM 463:464 PM 463:464 PM 463:464 The objective of the study was to identify and to characterize RCA binding glycoprotein of the bovine sperm plasma membranes (PM). 24818024 10 83 theme potential 1449:1457 arg1 role 1459:1462 a potential role 1447:1462 a potential role 1447:1462 Our biochemical results provide evidence on the presence of TEX101 in bovine epididymal sperm plasma membranes and may have a potential role in sperm-egg interaction. 24818024 8 84 theme TEX101 1032:1037 arg1 polypeptide 1039:1049 The native TEX101 polypeptide 1021:1049 The native TEX101 polypeptide 1021:1049 The native TEX101 polypeptide contains ~17 kDa N-linked oligosaccharides and the polypeptide is anchored to sperm membrane via a glycosylphosphatidylinositol lipid linkage. 24818024 10 85 from presence 1371:1378 arg1 membranes 1424:1432 bovine epididymal sperm plasma membranes 1393:1432 bovine epididymal sperm plasma membranes 1393:1432 Our biochemical results provide evidence on the presence of TEX101 in bovine epididymal sperm plasma membranes and may have a potential role in sperm-egg interaction. 24818024 4 86 theme PM 506:507 arg1 blots 475:479 Lectin blots 468:479 Lectin blots of caput and cauda sperm PM 468:507 Lectin blots of caput and cauda sperm PM revealed a 38 kDa polypeptide exhibiting the highest affinity to RCA among the several major RCA binding polypeptides. 24818024 3 87 theme membranes 452:460 arg1 glycoprotein 412:423 RCA binding glycoprotein 400:423 RCA binding glycoprotein of the bovine sperm plasma membranes (PM) 400:465 The objective of the study was to identify and to characterize RCA binding glycoprotein of the bovine sperm plasma membranes (PM). 24818024 0 88 theme Epididymal 56:65 arg1 Spermatozoa 67:77 Bovine Epididymal Spermatozoa 49:77 Bovine Epididymal Spermatozoa 49:77 Identification and Characterization of TEX101 in Bovine Epididymal Spermatozoa. 24818024 8 89 theme N-linked 1068:1075 arg1 oligosaccharides 1077:1092 ~17 kDa N-linked oligosaccharides 1060:1092 ~17 kDa N-linked oligosaccharides 1060:1092 The native TEX101 polypeptide contains ~17 kDa N-linked oligosaccharides and the polypeptide is anchored to sperm membrane via a glycosylphosphatidylinositol lipid linkage. 24818024 3 90 theme RCA 400:402 arg1 glycoprotein 412:423 RCA binding glycoprotein 400:423 RCA binding glycoprotein of the bovine sperm plasma membranes (PM) 400:465 The objective of the study was to identify and to characterize RCA binding glycoprotein of the bovine sperm plasma membranes (PM). 24818024 10 91 theme biochemical 1327:1337 arg1 results 1339:1345 Our biochemical results 1323:1345 Our biochemical results 1323:1345 Our biochemical results provide evidence on the presence of TEX101 in bovine epididymal sperm plasma membranes and may have a potential role in sperm-egg interaction. 24818024 1 92 from presence 108:115 arg1 spermatozoa 188:198 mammalian spermatozoa 178:198 mammalian spermatozoa 178:198 Several studies exhibit the presence of Ricinus Communis Agglutinin I (RCA) binding glycocalyx in mammalian spermatozoa. 24818024 6 93 theme Proteomic 789:797 arg1 identification 799:812 Proteomic identification 789:812 Proteomic identification 789:812 Proteomic identification yielded ten peptides that matched the sequence of Testis Expressed 101 protein (TEX101). 24818024 4 94 theme major 596:600 arg1 polypeptides 614:625 the several major RCA binding polypeptides 584:625 the several major RCA binding polypeptides 584:625 Lectin blots of caput and cauda sperm PM revealed a 38 kDa polypeptide exhibiting the highest affinity to RCA among the several major RCA binding polypeptides. 24818024 8 95 contain contains 1051:1058 arg1 polypeptide 1039:1049 The native TEX101 polypeptide 1021:1049 The native TEX101 polypeptide 1021:1049 The native TEX101 polypeptide contains ~17 kDa N-linked oligosaccharides and the polypeptide is anchored to sperm membrane via a glycosylphosphatidylinositol lipid linkage. 24818024 8 95 contain contains 1051:1058 arg2 oligosaccharides 1077:1092 ~17 kDa N-linked oligosaccharides 1060:1092 ~17 kDa N-linked oligosaccharides 1060:1092 The native TEX101 polypeptide contains ~17 kDa N-linked oligosaccharides and the polypeptide is anchored to sperm membrane via a glycosylphosphatidylinositol lipid linkage. 24357164 0 0 theme N 80:80 arg1 direction 87:95 the N to C direction 76:95 the N to C direction 76:95 A novel post-ligation thioesterification device enables peptide ligation in the N to C direction: synthetic study of human glycodelin. 24357164 6 1 theme N-ethylcysteine 878:892 arg1 residue 894:900 the N-ethylcysteine residue 874:900 the N-ethylcysteine residue 874:900 After deprotection of acetamidomethyl group on the N-ethylcysteine residue, the peptide was thioesterified by N-alkylcysteine-assisted method. 24357164 1 2 link N-linked 196:203 arg1 glycans 205:211 two N-linked glycans 192:211 two N-linked glycans 192:211 Human glycodelin consists of 162 amino acid residues and two N-linked glycans at Asn(28) and Asn(63) . 24357164 4 3 theme thioesterification 637:654 arg1 device 656:661 a post-ligation thioesterification device 621:661 a post-ligation thioesterification device 621:661 At the C-terminus of the second segment, N-ethyl-S-acetamidomethyl-cysteine was attached as a post-ligation thioesterification device. 24357164 4 3 theme thioesterification 637:654 arg1 N-ethyl-S-acetamidomethyl-cysteine 570:603 N-ethyl-S-acetamidomethyl-cysteine 570:603 N-ethyl-S-acetamidomethyl-cysteine 570:603 At the C-terminus of the second segment, N-ethyl-S-acetamidomethyl-cysteine was attached as a post-ligation thioesterification device. 24357164 5 4 from site 751:754 arg1 NCL 736:738 the homocysteine-mediated NCL 710:738 the homocysteine-mediated NCL at Leu-Met site 710:754 The N-terminal two segments were condensed by the homocysteine-mediated NCL at Leu-Met site, and the product was methylated to convert homocysteine to methionine. 24357164 7 5 theme segments 1075:1082 arg1 NCL 1051:1053 the NCL 1047:1053 the NCL of third and fourth segments 1047:1082 The product was then ligated with the C-terminal half, which was obtained by the NCL of third and fourth segments, to give the full-length glycodelin. 24357164 3 6 theme solid-phase 498:508 arg1 synthesis 518:526 9-fluorenylmethoxycarbonyl based solid-phase peptide synthesis 465:526 9-fluorenylmethoxycarbonyl based solid-phase peptide synthesis 465:526 The four peptide segments corresponding to 1-31, 32-65, 66-105 and 106-162 sequences were synthesized by 9-fluorenylmethoxycarbonyl based solid-phase peptide synthesis. 24357164 0 7 theme C 85:85 arg1 direction 87:95 the N to C direction 76:95 the N to C direction 76:95 A novel post-ligation thioesterification device enables peptide ligation in the N to C direction: synthetic study of human glycodelin. 24357164 0 8 theme synthetic 98:106 arg1 study 108:112 synthetic study 98:112 synthetic study of human glycodelin 98:132 A novel post-ligation thioesterification device enables peptide ligation in the N to C direction: synthetic study of human glycodelin. 24357164 6 9 theme group 865:869 arg1 deprotection 833:844 deprotection 833:844 deprotection of acetamidomethyl group on the N-ethylcysteine residue 833:900 After deprotection of acetamidomethyl group on the N-ethylcysteine residue, the peptide was thioesterified by N-alkylcysteine-assisted method. 24357164 0 10 dep direction 87:95 arg1 to 82:83 to 82:83 to 82:83 A novel post-ligation thioesterification device enables peptide ligation in the N to C direction: synthetic study of human glycodelin. 24357164 1 11 theme amino 168:172 arg1 residues 179:186 162 amino acid residues 164:186 162 amino acid residues 164:186 Human glycodelin consists of 162 amino acid residues and two N-linked glycans at Asn(28) and Asn(63) . 24357164 7 12 theme full-length 1097:1107 arg1 glycodelin 1109:1118 the full-length glycodelin 1093:1118 the full-length glycodelin 1093:1118 The product was then ligated with the C-terminal half, which was obtained by the NCL of third and fourth segments, to give the full-length glycodelin. 24357164 6 13 theme acetamidomethyl 849:863 arg1 group 865:869 acetamidomethyl group 849:869 acetamidomethyl group 849:869 After deprotection of acetamidomethyl group on the N-ethylcysteine residue, the peptide was thioesterified by N-alkylcysteine-assisted method. 24357164 7 14 theme fourth 1068:1073 arg1 segments 1075:1082 third and fourth segments 1058:1082 third and fourth segments 1058:1082 The product was then ligated with the C-terminal half, which was obtained by the NCL of third and fourth segments, to give the full-length glycodelin. 24357164 2 15 theme chemical 315:322 arg1 NCL 334:336 NCL 334:336 NCL 334:336 In this study, we synthesized it by a fully convergent strategy using native chemical ligation (NCL) in N to C direction. 24357164 2 15 theme chemical 315:322 arg1 ligation 324:331 native chemical ligation 308:331 native chemical ligation (NCL) 308:337 In this study, we synthesized it by a fully convergent strategy using native chemical ligation (NCL) in N to C direction. 24357164 0 16 theme novel 2:6 arg1 device 41:46 A novel post-ligation thioesterification device 0:46 A novel post-ligation thioesterification device 0:46 A novel post-ligation thioesterification device enables peptide ligation in the N to C direction: synthetic study of human glycodelin. 24357164 2 17 dep direction 349:357 arg1 N 342:342 N 342:342 N 342:342 In this study, we synthesized it by a fully convergent strategy using native chemical ligation (NCL) in N to C direction. 24357164 3 18 theme 9-fluorenylmethoxycarbonyl 465:490 arg1 synthesis 518:526 9-fluorenylmethoxycarbonyl based solid-phase peptide synthesis 465:526 9-fluorenylmethoxycarbonyl based solid-phase peptide synthesis 465:526 The four peptide segments corresponding to 1-31, 32-65, 66-105 and 106-162 sequences were synthesized by 9-fluorenylmethoxycarbonyl based solid-phase peptide synthesis. 24357164 2 19 theme native 308:313 arg1 NCL 334:336 NCL 334:336 NCL 334:336 In this study, we synthesized it by a fully convergent strategy using native chemical ligation (NCL) in N to C direction. 24357164 2 19 theme native 308:313 arg1 ligation 324:331 native chemical ligation 308:331 native chemical ligation (NCL) 308:337 In this study, we synthesized it by a fully convergent strategy using native chemical ligation (NCL) in N to C direction. 24357164 2 20 theme C 347:347 arg1 direction 349:357 C direction 347:357 C direction 347:357 In this study, we synthesized it by a fully convergent strategy using native chemical ligation (NCL) in N to C direction. 24357164 5 21 theme N-terminal 668:677 arg1 segments 683:690 The N-terminal two segments 664:690 The N-terminal two segments 664:690 The N-terminal two segments were condensed by the homocysteine-mediated NCL at Leu-Met site, and the product was methylated to convert homocysteine to methionine. 24357164 7 22 theme third 1058:1062 arg1 segments 1075:1082 third and fourth segments 1058:1082 third and fourth segments 1058:1082 The product was then ligated with the C-terminal half, which was obtained by the NCL of third and fourth segments, to give the full-length glycodelin. 24357164 3 23 theme based 492:496 arg1 synthesis 518:526 9-fluorenylmethoxycarbonyl based solid-phase peptide synthesis 465:526 9-fluorenylmethoxycarbonyl based solid-phase peptide synthesis 465:526 The four peptide segments corresponding to 1-31, 32-65, 66-105 and 106-162 sequences were synthesized by 9-fluorenylmethoxycarbonyl based solid-phase peptide synthesis. 24357164 1 24 theme acid 174:177 arg1 residues 179:186 162 amino acid residues 164:186 162 amino acid residues 164:186 Human glycodelin consists of 162 amino acid residues and two N-linked glycans at Asn(28) and Asn(63) . 24357164 0 25 theme thioesterification 22:39 arg1 device 41:46 A novel post-ligation thioesterification device 0:46 A novel post-ligation thioesterification device 0:46 A novel post-ligation thioesterification device enables peptide ligation in the N to C direction: synthetic study of human glycodelin. 24357164 4 26 theme second 554:559 arg1 segment 561:567 the second segment 550:567 the second segment 550:567 At the C-terminus of the second segment, N-ethyl-S-acetamidomethyl-cysteine was attached as a post-ligation thioesterification device. 24357164 0 27 theme post-ligation 8:20 arg1 device 41:46 A novel post-ligation thioesterification device 0:46 A novel post-ligation thioesterification device 0:46 A novel post-ligation thioesterification device enables peptide ligation in the N to C direction: synthetic study of human glycodelin. 24357164 6 28 theme N-alkylcysteine-assisted 937:960 arg1 method 962:967 N-alkylcysteine-assisted method 937:967 N-alkylcysteine-assisted method 937:967 After deprotection of acetamidomethyl group on the N-ethylcysteine residue, the peptide was thioesterified by N-alkylcysteine-assisted method. 24357164 1 29 from Asn 228:230 arg1 glycans 205:211 two N-linked glycans 192:211 two N-linked glycans 192:211 Human glycodelin consists of 162 amino acid residues and two N-linked glycans at Asn(28) and Asn(63) . 24357164 1 29 from Asn 228:230 arg1 residues 179:186 162 amino acid residues 164:186 162 amino acid residues 164:186 Human glycodelin consists of 162 amino acid residues and two N-linked glycans at Asn(28) and Asn(63) . 24357164 3 30 theme peptide 369:375 arg1 segments 377:384 The four peptide segments 360:384 The four peptide segments corresponding to 1-31, 32-65, 66-105 and 106-162 sequences 360:443 The four peptide segments corresponding to 1-31, 32-65, 66-105 and 106-162 sequences were synthesized by 9-fluorenylmethoxycarbonyl based solid-phase peptide synthesis. 24357164 5 31 theme Leu-Met 743:749 arg1 site 751:754 Leu-Met site 743:754 Leu-Met site 743:754 The N-terminal two segments were condensed by the homocysteine-mediated NCL at Leu-Met site, and the product was methylated to convert homocysteine to methionine. 24357164 0 32 theme glycodelin 123:132 arg1 study 108:112 synthetic study 98:112 synthetic study of human glycodelin 98:132 A novel post-ligation thioesterification device enables peptide ligation in the N to C direction: synthetic study of human glycodelin. 24357164 0 33 theme human 117:121 arg1 glycodelin 123:132 human glycodelin 117:132 human glycodelin 117:132 A novel post-ligation thioesterification device enables peptide ligation in the N to C direction: synthetic study of human glycodelin. 24357164 4 34 attach attached 609:616 arg2 device 656:661 a post-ligation thioesterification device 621:661 a post-ligation thioesterification device 621:661 At the C-terminus of the second segment, N-ethyl-S-acetamidomethyl-cysteine was attached as a post-ligation thioesterification device. 24357164 4 34 attach attached 609:616 arg2 N-ethyl-S-acetamidomethyl-cysteine 570:603 N-ethyl-S-acetamidomethyl-cysteine 570:603 N-ethyl-S-acetamidomethyl-cysteine 570:603 At the C-terminus of the second segment, N-ethyl-S-acetamidomethyl-cysteine was attached as a post-ligation thioesterification device. 24357164 4 34 attach attached 609:616 arg3 C-terminus 536:545 the C-terminus 532:545 the C-terminus of the second segment 532:567 At the C-terminus of the second segment, N-ethyl-S-acetamidomethyl-cysteine was attached as a post-ligation thioesterification device. 24357164 6 35 from deprotection 833:844 arg1 residue 894:900 the N-ethylcysteine residue 874:900 the N-ethylcysteine residue 874:900 After deprotection of acetamidomethyl group on the N-ethylcysteine residue, the peptide was thioesterified by N-alkylcysteine-assisted method. 24357164 1 36 theme N-linked 196:203 arg1 glycans 205:211 two N-linked glycans 192:211 two N-linked glycans 192:211 Human glycodelin consists of 162 amino acid residues and two N-linked glycans at Asn(28) and Asn(63) . 24357164 1 37 from Asn 216:218 arg1 glycans 205:211 two N-linked glycans 192:211 two N-linked glycans 192:211 Human glycodelin consists of 162 amino acid residues and two N-linked glycans at Asn(28) and Asn(63) . 24357164 1 37 from Asn 216:218 arg1 residues 179:186 162 amino acid residues 164:186 162 amino acid residues 164:186 Human glycodelin consists of 162 amino acid residues and two N-linked glycans at Asn(28) and Asn(63) . 24357164 0 38 dep enables 48:54 arg1 study 108:112 synthetic study 98:112 synthetic study of human glycodelin 98:132 A novel post-ligation thioesterification device enables peptide ligation in the N to C direction: synthetic study of human glycodelin. 24357164 7 39 theme C-terminal 1008:1017 arg1 half 1019:1022 the C-terminal half 1004:1022 the C-terminal half 1004:1022 The product was then ligated with the C-terminal half, which was obtained by the NCL of third and fourth segments, to give the full-length glycodelin. 24357164 0 40 theme peptide 56:62 arg1 ligation 64:71 peptide ligation 56:71 peptide ligation 56:71 A novel post-ligation thioesterification device enables peptide ligation in the N to C direction: synthetic study of human glycodelin. 24357164 3 41 theme peptide 510:516 arg1 synthesis 518:526 9-fluorenylmethoxycarbonyl based solid-phase peptide synthesis 465:526 9-fluorenylmethoxycarbonyl based solid-phase peptide synthesis 465:526 The four peptide segments corresponding to 1-31, 32-65, 66-105 and 106-162 sequences were synthesized by 9-fluorenylmethoxycarbonyl based solid-phase peptide synthesis. 24357164 1 42 theme Human 135:139 arg1 glycodelin 141:150 Human glycodelin 135:150 Human glycodelin 135:150 Human glycodelin consists of 162 amino acid residues and two N-linked glycans at Asn(28) and Asn(63) . 24357164 4 43 theme segment 561:567 arg1 C-terminus 536:545 the C-terminus 532:545 the C-terminus of the second segment 532:567 At the C-terminus of the second segment, N-ethyl-S-acetamidomethyl-cysteine was attached as a post-ligation thioesterification device. 24357164 4 44 theme post-ligation 623:635 arg1 device 656:661 a post-ligation thioesterification device 621:661 a post-ligation thioesterification device 621:661 At the C-terminus of the second segment, N-ethyl-S-acetamidomethyl-cysteine was attached as a post-ligation thioesterification device. 24357164 4 44 theme post-ligation 623:635 arg1 N-ethyl-S-acetamidomethyl-cysteine 570:603 N-ethyl-S-acetamidomethyl-cysteine 570:603 N-ethyl-S-acetamidomethyl-cysteine 570:603 At the C-terminus of the second segment, N-ethyl-S-acetamidomethyl-cysteine was attached as a post-ligation thioesterification device. 24357164 5 45 theme homocysteine-mediated 714:734 arg1 NCL 736:738 the homocysteine-mediated NCL 710:738 the homocysteine-mediated NCL at Leu-Met site 710:754 The N-terminal two segments were condensed by the homocysteine-mediated NCL at Leu-Met site, and the product was methylated to convert homocysteine to methionine. 24357164 2 46 theme convergent 282:291 arg1 strategy 293:300 a fully convergent strategy 274:300 a fully convergent strategy using native chemical ligation (NCL) 274:337 In this study, we synthesized it by a fully convergent strategy using native chemical ligation (NCL) in N to C direction. 29085762 2 0 theme polymerase 460:469 arg1 RT-PCR 487:492 RT-PCR 487:492 RT-PCR 487:492 To investigate the RSV burden in Thailand over four consecutive years (January 2012 to December 2015), we screened 3,306 samples obtained from children ≤5 years old with acute respiratory tract infection using semi-nested reverse-transcription polymerase chain reaction (RT-PCR). 29085762 2 0 theme polymerase 460:469 arg1 reaction 477:484 semi-nested reverse-transcription polymerase chain reaction 426:484 semi-nested reverse-transcription polymerase chain reaction (RT-PCR) 426:493 To investigate the RSV burden in Thailand over four consecutive years (January 2012 to December 2015), we screened 3,306 samples obtained from children ≤5 years old with acute respiratory tract infection using semi-nested reverse-transcription polymerase chain reaction (RT-PCR). 29085762 7 1 theme N-linked 1163:1170 arg1 site 1186:1189 highly conserved N-linked glycosylation site 1146:1189 highly conserved N-linked glycosylation site 1146:1189 Predicted amino acid sequence from the partial G region showed highly conserved N-linked glycosylation site at residue N237 among all RSV-A ON1 strains (68/68), and at residues N296 (86/87) and N310 (87/87) among RSV-B BA9 strains. 29085762 8 2 from variations 1381:1390 arg1 gene 1401:1404 the G gene 1395:1404 the G gene 1395:1404 Positive selection of key residues combined with notable sequence variations on the G gene contributed to the continued circulation of this rapidly evolving virus. 29085762 7 3 theme RSV-B 1296:1300 arg1 strains 1306:1312 RSV-B BA9 strains 1296:1312 RSV-B BA9 strains 1296:1312 Predicted amino acid sequence from the partial G region showed highly conserved N-linked glycosylation site at residue N237 among all RSV-A ON1 strains (68/68), and at residues N296 (86/87) and N310 (87/87) among RSV-B BA9 strains. 29085762 2 4 theme reverse-transcription 438:458 arg1 RT-PCR 487:492 RT-PCR 487:492 RT-PCR 487:492 To investigate the RSV burden in Thailand over four consecutive years (January 2012 to December 2015), we screened 3,306 samples obtained from children ≤5 years old with acute respiratory tract infection using semi-nested reverse-transcription polymerase chain reaction (RT-PCR). 29085762 2 4 theme reverse-transcription 438:458 arg1 reaction 477:484 semi-nested reverse-transcription polymerase chain reaction 426:484 semi-nested reverse-transcription polymerase chain reaction (RT-PCR) 426:493 To investigate the RSV burden in Thailand over four consecutive years (January 2012 to December 2015), we screened 3,306 samples obtained from children ≤5 years old with acute respiratory tract infection using semi-nested reverse-transcription polymerase chain reaction (RT-PCR). 29085762 8 5 theme continued 1425:1433 arg1 circulation 1435:1445 the continued circulation 1421:1445 the continued circulation of this rapidly evolving virus 1421:1476 Positive selection of key residues combined with notable sequence variations on the G gene contributed to the continued circulation of this rapidly evolving virus. 29085762 7 6 theme BA9 1302:1304 arg1 strains 1306:1312 RSV-B BA9 strains 1296:1312 RSV-B BA9 strains 1296:1312 Predicted amino acid sequence from the partial G region showed highly conserved N-linked glycosylation site at residue N237 among all RSV-A ON1 strains (68/68), and at residues N296 (86/87) and N310 (87/87) among RSV-B BA9 strains. 29085762 5 7 theme ON1 893:895 arg1 genotype 897:904 ON1 genotype 893:904 ON1 genotype 893:904 The majority (57.4%, 159/277) of the RSV belonged to subgroup A (RSV-A), of which NA1 genotype was the most common in 2012 while ON1 genotype became prevalent the following year. 29085762 3 8 theme July 609:612 arg1 months 599:604 the rainy months 589:604 the rainy months of July to November 589:624 In all, 8.4% (277/3,306) of the specimens tested positive for RSV, most of which appeared in the rainy months of July to November. 29085762 4 9 theme glycoprotein 669:680 arg1 gene 682:685 the G glycoprotein gene 663:685 the G glycoprotein gene 663:685 We then genotyped RSV by sequencing the G glycoprotein gene and performed phylogenetic analysis to determine the RSV antigenic subgroup. 29085762 8 10 theme evolving 1463:1470 arg1 virus 1472:1476 this rapidly evolving virus 1450:1476 this rapidly evolving virus 1450:1476 Positive selection of key residues combined with notable sequence variations on the G gene contributed to the continued circulation of this rapidly evolving virus. 29085762 7 11 theme ON1 1223:1225 arg1 68/68 1236:1240 68/68 1236:1240 68/68 1236:1240 Predicted amino acid sequence from the partial G region showed highly conserved N-linked glycosylation site at residue N237 among all RSV-A ON1 strains (68/68), and at residues N296 (86/87) and N310 (87/87) among RSV-B BA9 strains. 29085762 7 11 theme ON1 1223:1225 arg1 strains 1227:1233 all RSV-A ON1 strains 1213:1233 all RSV-A ON1 strains (68/68) 1213:1241 Predicted amino acid sequence from the partial G region showed highly conserved N-linked glycosylation site at residue N237 among all RSV-A ON1 strains (68/68), and at residues N296 (86/87) and N310 (87/87) among RSV-B BA9 strains. 29085762 8 12 theme sequence 1372:1379 arg1 variations 1381:1390 notable sequence variations 1364:1390 notable sequence variations on the G gene 1364:1404 Positive selection of key residues combined with notable sequence variations on the G gene contributed to the continued circulation of this rapidly evolving virus. 29085762 4 13 theme G 667:667 arg1 gene 682:685 the G glycoprotein gene 663:685 the G glycoprotein gene 663:685 We then genotyped RSV by sequencing the G glycoprotein gene and performed phylogenetic analysis to determine the RSV antigenic subgroup. 29085762 5 14 theme subgroup 817:824 arg1 RSV-A 829:833 RSV-A 829:833 RSV-A 829:833 The majority (57.4%, 159/277) of the RSV belonged to subgroup A (RSV-A), of which NA1 genotype was the most common in 2012 while ON1 genotype became prevalent the following year. 29085762 5 14 theme subgroup 817:824 arg1 A 826:826 subgroup A 817:826 subgroup A (RSV-A) 817:834 The majority (57.4%, 159/277) of the RSV belonged to subgroup A (RSV-A), of which NA1 genotype was the most common in 2012 while ON1 genotype became prevalent the following year. 29085762 7 15 theme acid 1099:1102 arg1 sequence 1104:1111 Predicted amino acid sequence 1083:1111 Predicted amino acid sequence from the partial G region 1083:1137 Predicted amino acid sequence from the partial G region showed highly conserved N-linked glycosylation site at residue N237 among all RSV-A ON1 strains (68/68), and at residues N296 (86/87) and N310 (87/87) among RSV-B BA9 strains. 29085762 1 16 theme acute 135:139 arg1 infection 165:173 acute lower respiratory tract infection 135:173 acute lower respiratory tract infection in infants and young children worldwide 135:213 Respiratory syncytial virus (RSV) causes acute lower respiratory tract infection in infants and young children worldwide. 29085762 6 17 dep BA10 1068:1071 arg1 some 1063:1066 some 1063:1066 some 1063:1066 Among samples tested positive for RSV-B subgroup B (RSV-B) (42.6%, 118/277), most were genotype BA9 (92.6%, 87/94) with some BA10 and BA-C. 29085762 6 18 theme RSV-B 977:981 arg1 RSV-B 995:999 RSV-B 995:999 RSV-B 995:999 Among samples tested positive for RSV-B subgroup B (RSV-B) (42.6%, 118/277), most were genotype BA9 (92.6%, 87/94) with some BA10 and BA-C. 29085762 6 18 theme RSV-B 977:981 arg1 B 992:992 RSV-B subgroup B 977:992 RSV-B subgroup B (RSV-B) (42.6%, 118/277) 977:1017 Among samples tested positive for RSV-B subgroup B (RSV-B) (42.6%, 118/277), most were genotype BA9 (92.6%, 87/94) with some BA10 and BA-C. 29085762 2 19 theme acute 386:390 arg1 infection 410:418 acute respiratory tract infection 386:418 acute respiratory tract infection using semi-nested reverse-transcription polymerase chain reaction (RT-PCR) 386:493 To investigate the RSV burden in Thailand over four consecutive years (January 2012 to December 2015), we screened 3,306 samples obtained from children ≤5 years old with acute respiratory tract infection using semi-nested reverse-transcription polymerase chain reaction (RT-PCR). 29085762 7 20 from region 1132:1137 arg1 sequence 1104:1111 Predicted amino acid sequence 1083:1111 Predicted amino acid sequence from the partial G region 1083:1137 Predicted amino acid sequence from the partial G region showed highly conserved N-linked glycosylation site at residue N237 among all RSV-A ON1 strains (68/68), and at residues N296 (86/87) and N310 (87/87) among RSV-B BA9 strains. 29085762 1 21 theme lower 141:145 arg1 tract 159:163 lower respiratory tract 141:163 acute lower respiratory tract infection in infants and young children worldwide 135:213 Respiratory syncytial virus (RSV) causes acute lower respiratory tract infection in infants and young children worldwide. 29085762 2 22 theme respiratory 392:402 arg1 infection 410:418 acute respiratory tract infection 386:418 acute respiratory tract infection using semi-nested reverse-transcription polymerase chain reaction (RT-PCR) 386:493 To investigate the RSV burden in Thailand over four consecutive years (January 2012 to December 2015), we screened 3,306 samples obtained from children ≤5 years old with acute respiratory tract infection using semi-nested reverse-transcription polymerase chain reaction (RT-PCR). 29085762 7 23 dep residues 1251:1258 arg1 86/87 1266:1270 86/87 1266:1270 86/87 1266:1270 Predicted amino acid sequence from the partial G region showed highly conserved N-linked glycosylation site at residue N237 among all RSV-A ON1 strains (68/68), and at residues N296 (86/87) and N310 (87/87) among RSV-B BA9 strains. 29085762 7 23 dep residues 1251:1258 arg1 N310 1277:1280 N310 1277:1280 N310 1277:1280 Predicted amino acid sequence from the partial G region showed highly conserved N-linked glycosylation site at residue N237 among all RSV-A ON1 strains (68/68), and at residues N296 (86/87) and N310 (87/87) among RSV-B BA9 strains. 29085762 7 23 dep residues 1251:1258 arg1 N296 1260:1263 N296 1260:1263 N296 1260:1263 Predicted amino acid sequence from the partial G region showed highly conserved N-linked glycosylation site at residue N237 among all RSV-A ON1 strains (68/68), and at residues N296 (86/87) and N310 (87/87) among RSV-B BA9 strains. 29085762 7 23 dep residues 1251:1258 arg1 residues 1251:1258 residues N296 (86/87) and N310 (87/87) 1251:1288 residues N296 (86/87) and N310 (87/87) 1251:1288 Predicted amino acid sequence from the partial G region showed highly conserved N-linked glycosylation site at residue N237 among all RSV-A ON1 strains (68/68), and at residues N296 (86/87) and N310 (87/87) among RSV-B BA9 strains. 29085762 7 23 dep residues 1251:1258 arg1 87/87 1283:1287 87/87 1283:1287 87/87 1283:1287 Predicted amino acid sequence from the partial G region showed highly conserved N-linked glycosylation site at residue N237 among all RSV-A ON1 strains (68/68), and at residues N296 (86/87) and N310 (87/87) among RSV-B BA9 strains. 29085762 6 24 with BA9 1039:1041 arg1 BA-C 1077:1080 BA-C 1077:1080 BA-C 1077:1080 Among samples tested positive for RSV-B subgroup B (RSV-B) (42.6%, 118/277), most were genotype BA9 (92.6%, 87/94) with some BA10 and BA-C. 29085762 6 24 with BA9 1039:1041 arg1 BA10 1068:1071 BA10 1068:1071 BA10 1068:1071 Among samples tested positive for RSV-B subgroup B (RSV-B) (42.6%, 118/277), most were genotype BA9 (92.6%, 87/94) with some BA10 and BA-C. 29085762 5 25 theme A 826:826 arg1 genotype 850:857 NA1 genotype 846:857 NA1 genotype 846:857 The majority (57.4%, 159/277) of the RSV belonged to subgroup A (RSV-A), of which NA1 genotype was the most common in 2012 while ON1 genotype became prevalent the following year. 29085762 5 25 theme A 826:826 arg1 common 872:877 common 872:877 common 872:877 The majority (57.4%, 159/277) of the RSV belonged to subgroup A (RSV-A), of which NA1 genotype was the most common in 2012 while ON1 genotype became prevalent the following year. 29085762 1 26 theme respiratory 147:157 arg1 tract 159:163 lower respiratory tract 141:163 acute lower respiratory tract infection in infants and young children worldwide 135:213 Respiratory syncytial virus (RSV) causes acute lower respiratory tract infection in infants and young children worldwide. 29085762 0 27 theme Respiratory 0:10 arg1 genotypes 28:36 Respiratory syncytial virus genotypes 0:36 Respiratory syncytial virus genotypes NA1, ON1, and BA9 0:54 Respiratory syncytial virus genotypes NA1, ON1, and BA9 are prevalent in Thailand, 2012-2015. 29085762 0 27 theme Respiratory 0:10 arg1 ON1 43:45 ON1 43:45 ON1 43:45 Respiratory syncytial virus genotypes NA1, ON1, and BA9 are prevalent in Thailand, 2012-2015. 29085762 0 27 theme Respiratory 0:10 arg1 BA9 52:54 BA9 52:54 BA9 52:54 Respiratory syncytial virus genotypes NA1, ON1, and BA9 are prevalent in Thailand, 2012-2015. 29085762 0 27 theme Respiratory 0:10 arg1 NA1 38:40 NA1 38:40 NA1 38:40 Respiratory syncytial virus genotypes NA1, ON1, and BA9 are prevalent in Thailand, 2012-2015. 29085762 7 28 theme RSV-A 1217:1221 arg1 68/68 1236:1240 68/68 1236:1240 68/68 1236:1240 Predicted amino acid sequence from the partial G region showed highly conserved N-linked glycosylation site at residue N237 among all RSV-A ON1 strains (68/68), and at residues N296 (86/87) and N310 (87/87) among RSV-B BA9 strains. 29085762 7 28 theme RSV-A 1217:1221 arg1 strains 1227:1233 all RSV-A ON1 strains 1213:1233 all RSV-A ON1 strains (68/68) 1213:1241 Predicted amino acid sequence from the partial G region showed highly conserved N-linked glycosylation site at residue N237 among all RSV-A ON1 strains (68/68), and at residues N296 (86/87) and N310 (87/87) among RSV-B BA9 strains. 29085762 2 29 dep January 287:293 arg1 to 300:301 to 300:301 to 300:301 To investigate the RSV burden in Thailand over four consecutive years (January 2012 to December 2015), we screened 3,306 samples obtained from children ≤5 years old with acute respiratory tract infection using semi-nested reverse-transcription polymerase chain reaction (RT-PCR). 29085762 2 29 dep January 287:293 arg1 December 303:310 December 303:310 December 303:310 To investigate the RSV burden in Thailand over four consecutive years (January 2012 to December 2015), we screened 3,306 samples obtained from children ≤5 years old with acute respiratory tract infection using semi-nested reverse-transcription polymerase chain reaction (RT-PCR). 29085762 5 30 from 2012 882:885 arg1 genotype 850:857 NA1 genotype 846:857 NA1 genotype 846:857 The majority (57.4%, 159/277) of the RSV belonged to subgroup A (RSV-A), of which NA1 genotype was the most common in 2012 while ON1 genotype became prevalent the following year. 29085762 5 30 from 2012 882:885 arg1 common 872:877 common 872:877 common 872:877 The majority (57.4%, 159/277) of the RSV belonged to subgroup A (RSV-A), of which NA1 genotype was the most common in 2012 while ON1 genotype became prevalent the following year. 29085762 1 31 theme tract 159:163 arg1 infection 165:173 acute lower respiratory tract infection 135:173 acute lower respiratory tract infection in infants and young children worldwide 135:213 Respiratory syncytial virus (RSV) causes acute lower respiratory tract infection in infants and young children worldwide. 29085762 3 32 dep July 609:612 arg1 to 614:615 to 614:615 to 614:615 In all, 8.4% (277/3,306) of the specimens tested positive for RSV, most of which appeared in the rainy months of July to November. 29085762 3 32 dep July 609:612 arg1 November 617:624 November 617:624 November 617:624 In all, 8.4% (277/3,306) of the specimens tested positive for RSV, most of which appeared in the rainy months of July to November. 29085762 6 33 theme genotype 1030:1037 arg1 BA9 1039:1041 genotype BA9 1030:1041 genotype BA9 (92.6%, 87/94) 1030:1056 Among samples tested positive for RSV-B subgroup B (RSV-B) (42.6%, 118/277), most were genotype BA9 (92.6%, 87/94) with some BA10 and BA-C. 29085762 2 34 theme consecutive 268:278 arg1 years 280:284 four consecutive years 263:284 four consecutive years (January 2012 to December 2015) 263:316 To investigate the RSV burden in Thailand over four consecutive years (January 2012 to December 2015), we screened 3,306 samples obtained from children ≤5 years old with acute respiratory tract infection using semi-nested reverse-transcription polymerase chain reaction (RT-PCR). 29085762 5 35 dep % 782:782 arg1 159/277 785:791 159/277 785:791 159/277 785:791 The majority (57.4%, 159/277) of the RSV belonged to subgroup A (RSV-A), of which NA1 genotype was the most common in 2012 while ON1 genotype became prevalent the following year. 29085762 7 36 theme Predicted 1083:1091 arg1 sequence 1104:1111 Predicted amino acid sequence 1083:1111 Predicted amino acid sequence from the partial G region 1083:1137 Predicted amino acid sequence from the partial G region showed highly conserved N-linked glycosylation site at residue N237 among all RSV-A ON1 strains (68/68), and at residues N296 (86/87) and N310 (87/87) among RSV-B BA9 strains. 29085762 2 37 theme old 377:379 arg1 children 359:366 children 359:366 children ≤5 years old 359:379 To investigate the RSV burden in Thailand over four consecutive years (January 2012 to December 2015), we screened 3,306 samples obtained from children ≤5 years old with acute respiratory tract infection using semi-nested reverse-transcription polymerase chain reaction (RT-PCR). 29085762 0 38 from prevalent 60:68 arg1 Thailand 73:80 Thailand 73:80 Thailand 73:80 Respiratory syncytial virus genotypes NA1, ON1, and BA9 are prevalent in Thailand, 2012-2015. 29085762 5 39 from common 872:877 arg1 2012 882:885 2012 882:885 2012 882:885 The majority (57.4%, 159/277) of the RSV belonged to subgroup A (RSV-A), of which NA1 genotype was the most common in 2012 while ON1 genotype became prevalent the following year. 29085762 7 40 theme amino 1093:1097 arg1 sequence 1104:1111 Predicted amino acid sequence 1083:1111 Predicted amino acid sequence from the partial G region 1083:1137 Predicted amino acid sequence from the partial G region showed highly conserved N-linked glycosylation site at residue N237 among all RSV-A ON1 strains (68/68), and at residues N296 (86/87) and N310 (87/87) among RSV-B BA9 strains. 29085762 2 41 theme semi-nested 426:436 arg1 RT-PCR 487:492 RT-PCR 487:492 RT-PCR 487:492 To investigate the RSV burden in Thailand over four consecutive years (January 2012 to December 2015), we screened 3,306 samples obtained from children ≤5 years old with acute respiratory tract infection using semi-nested reverse-transcription polymerase chain reaction (RT-PCR). 29085762 2 41 theme semi-nested 426:436 arg1 reaction 477:484 semi-nested reverse-transcription polymerase chain reaction 426:484 semi-nested reverse-transcription polymerase chain reaction (RT-PCR) 426:493 To investigate the RSV burden in Thailand over four consecutive years (January 2012 to December 2015), we screened 3,306 samples obtained from children ≤5 years old with acute respiratory tract infection using semi-nested reverse-transcription polymerase chain reaction (RT-PCR). 29085762 6 42 theme subgroup 983:990 arg1 RSV-B 995:999 RSV-B 995:999 RSV-B 995:999 Among samples tested positive for RSV-B subgroup B (RSV-B) (42.6%, 118/277), most were genotype BA9 (92.6%, 87/94) with some BA10 and BA-C. 29085762 6 42 theme subgroup 983:990 arg1 B 992:992 RSV-B subgroup B 977:992 RSV-B subgroup B (RSV-B) (42.6%, 118/277) 977:1017 Among samples tested positive for RSV-B subgroup B (RSV-B) (42.6%, 118/277), most were genotype BA9 (92.6%, 87/94) with some BA10 and BA-C. 29085762 5 43 theme following 927:935 arg1 year 937:940 the following year 923:940 the following year 923:940 The majority (57.4%, 159/277) of the RSV belonged to subgroup A (RSV-A), of which NA1 genotype was the most common in 2012 while ON1 genotype became prevalent the following year. 29085762 3 44 theme specimens 528:536 arg1 specimens 528:536 the specimens 524:536 the specimens 524:536 In all, 8.4% (277/3,306) of the specimens tested positive for RSV, most of which appeared in the rainy months of July to November. 29085762 3 44 theme specimens 528:536 arg1 277/3,306 510:518 277/3,306 510:518 277/3,306 510:518 In all, 8.4% (277/3,306) of the specimens tested positive for RSV, most of which appeared in the rainy months of July to November. 29085762 3 44 theme specimens 528:536 arg1 % 507:507 8.4% 504:507 8.4% (277/3,306) of the specimens 504:536 In all, 8.4% (277/3,306) of the specimens tested positive for RSV, most of which appeared in the rainy months of July to November. 29085762 7 45 theme glycosylation 1172:1184 arg1 site 1186:1189 highly conserved N-linked glycosylation site 1146:1189 highly conserved N-linked glycosylation site 1146:1189 Predicted amino acid sequence from the partial G region showed highly conserved N-linked glycosylation site at residue N237 among all RSV-A ON1 strains (68/68), and at residues N296 (86/87) and N310 (87/87) among RSV-B BA9 strains. 29085762 7 46 theme conserved 1153:1161 arg1 site 1186:1189 highly conserved N-linked glycosylation site 1146:1189 highly conserved N-linked glycosylation site 1146:1189 Predicted amino acid sequence from the partial G region showed highly conserved N-linked glycosylation site at residue N237 among all RSV-A ON1 strains (68/68), and at residues N296 (86/87) and N310 (87/87) among RSV-B BA9 strains. 29085762 8 47 theme Positive 1315:1322 arg1 selection 1324:1332 Positive selection 1315:1332 Positive selection of key residues combined with notable sequence variations on the G gene 1315:1404 Positive selection of key residues combined with notable sequence variations on the G gene contributed to the continued circulation of this rapidly evolving virus. 29085762 7 48 link N-linked 1163:1170 arg1 site 1186:1189 highly conserved N-linked glycosylation site 1146:1189 highly conserved N-linked glycosylation site 1146:1189 Predicted amino acid sequence from the partial G region showed highly conserved N-linked glycosylation site at residue N237 among all RSV-A ON1 strains (68/68), and at residues N296 (86/87) and N310 (87/87) among RSV-B BA9 strains. 29085762 7 49 theme partial 1122:1128 arg1 region 1132:1137 the partial G region 1118:1137 the partial G region 1118:1137 Predicted amino acid sequence from the partial G region showed highly conserved N-linked glycosylation site at residue N237 among all RSV-A ON1 strains (68/68), and at residues N296 (86/87) and N310 (87/87) among RSV-B BA9 strains. 29085762 4 50 gly glycoprotein 669:680 arg1 glycoprotein 669:680 the G glycoprotein gene 663:685 the G glycoprotein gene 663:685 We then genotyped RSV by sequencing the G glycoprotein gene and performed phylogenetic analysis to determine the RSV antigenic subgroup. 29085762 4 51 theme antigenic 744:752 arg1 subgroup 754:761 the RSV antigenic subgroup 736:761 the RSV antigenic subgroup 736:761 We then genotyped RSV by sequencing the G glycoprotein gene and performed phylogenetic analysis to determine the RSV antigenic subgroup. 29085762 5 52 theme RSV 801:803 arg1 majority 768:775 The majority 764:775 The majority (57.4%, 159/277) of the RSV 764:803 The majority (57.4%, 159/277) of the RSV belonged to subgroup A (RSV-A), of which NA1 genotype was the most common in 2012 while ON1 genotype became prevalent the following year. 29085762 5 52 theme RSV 801:803 arg1 % 782:782 57.4% 778:782 57.4% 778:782 The majority (57.4%, 159/277) of the RSV belonged to subgroup A (RSV-A), of which NA1 genotype was the most common in 2012 while ON1 genotype became prevalent the following year. 29085762 2 53 theme tract 404:408 arg1 infection 410:418 acute respiratory tract infection 386:418 acute respiratory tract infection using semi-nested reverse-transcription polymerase chain reaction (RT-PCR) 386:493 To investigate the RSV burden in Thailand over four consecutive years (January 2012 to December 2015), we screened 3,306 samples obtained from children ≤5 years old with acute respiratory tract infection using semi-nested reverse-transcription polymerase chain reaction (RT-PCR). 29085762 7 54 gly glycosylation 1172:1184 arg2 site 1186:1189 highly conserved N-linked glycosylation site 1146:1189 highly conserved N-linked glycosylation site 1146:1189 Predicted amino acid sequence from the partial G region showed highly conserved N-linked glycosylation site at residue N237 among all RSV-A ON1 strains (68/68), and at residues N296 (86/87) and N310 (87/87) among RSV-B BA9 strains. 29085762 3 55 theme rainy 593:597 arg1 months 599:604 the rainy months 589:604 the rainy months of July to November 589:624 In all, 8.4% (277/3,306) of the specimens tested positive for RSV, most of which appeared in the rainy months of July to November. 29085762 4 56 theme RSV 740:742 arg1 subgroup 754:761 the RSV antigenic subgroup 736:761 the RSV antigenic subgroup 736:761 We then genotyped RSV by sequencing the G glycoprotein gene and performed phylogenetic analysis to determine the RSV antigenic subgroup. 29085762 1 57 from infection 165:173 arg1 infants 178:184 infants 178:184 infants 178:184 Respiratory syncytial virus (RSV) causes acute lower respiratory tract infection in infants and young children worldwide. 29085762 1 57 from infection 165:173 arg1 children 196:203 young children 190:203 young children worldwide 190:213 Respiratory syncytial virus (RSV) causes acute lower respiratory tract infection in infants and young children worldwide. 29085762 1 58 theme Respiratory 94:104 arg1 RSV 123:125 RSV 123:125 RSV 123:125 Respiratory syncytial virus (RSV) causes acute lower respiratory tract infection in infants and young children worldwide. 29085762 1 58 theme Respiratory 94:104 arg1 virus 116:120 Respiratory syncytial virus 94:120 Respiratory syncytial virus (RSV) 94:126 Respiratory syncytial virus (RSV) causes acute lower respiratory tract infection in infants and young children worldwide. 29085762 7 59 theme G 1130:1130 arg1 region 1132:1137 the partial G region 1118:1137 the partial G region 1118:1137 Predicted amino acid sequence from the partial G region showed highly conserved N-linked glycosylation site at residue N237 among all RSV-A ON1 strains (68/68), and at residues N296 (86/87) and N310 (87/87) among RSV-B BA9 strains. 29085762 0 60 dep genotypes 28:36 arg1 genotypes 28:36 Respiratory syncytial virus genotypes 0:36 Respiratory syncytial virus genotypes NA1, ON1, and BA9 0:54 Respiratory syncytial virus genotypes NA1, ON1, and BA9 are prevalent in Thailand, 2012-2015. 29085762 0 60 dep genotypes 28:36 arg1 ON1 43:45 ON1 43:45 ON1 43:45 Respiratory syncytial virus genotypes NA1, ON1, and BA9 are prevalent in Thailand, 2012-2015. 29085762 0 60 dep genotypes 28:36 arg1 BA9 52:54 BA9 52:54 BA9 52:54 Respiratory syncytial virus genotypes NA1, ON1, and BA9 are prevalent in Thailand, 2012-2015. 29085762 0 60 dep genotypes 28:36 arg1 NA1 38:40 NA1 38:40 NA1 38:40 Respiratory syncytial virus genotypes NA1, ON1, and BA9 are prevalent in Thailand, 2012-2015. 29085762 2 61 theme RSV 235:237 arg1 burden 239:244 the RSV burden 231:244 the RSV burden in Thailand 231:256 To investigate the RSV burden in Thailand over four consecutive years (January 2012 to December 2015), we screened 3,306 samples obtained from children ≤5 years old with acute respiratory tract infection using semi-nested reverse-transcription polymerase chain reaction (RT-PCR). 29085762 1 62 theme syncytial 106:114 arg1 RSV 123:125 RSV 123:125 RSV 123:125 Respiratory syncytial virus (RSV) causes acute lower respiratory tract infection in infants and young children worldwide. 29085762 1 62 theme syncytial 106:114 arg1 virus 116:120 Respiratory syncytial virus 94:120 Respiratory syncytial virus (RSV) 94:126 Respiratory syncytial virus (RSV) causes acute lower respiratory tract infection in infants and young children worldwide. 29085762 2 63 from burden 239:244 arg1 Thailand 249:256 Thailand 249:256 Thailand 249:256 To investigate the RSV burden in Thailand over four consecutive years (January 2012 to December 2015), we screened 3,306 samples obtained from children ≤5 years old with acute respiratory tract infection using semi-nested reverse-transcription polymerase chain reaction (RT-PCR). 29085762 1 64 theme young 190:194 arg1 children 196:203 young children 190:203 young children worldwide 190:213 Respiratory syncytial virus (RSV) causes acute lower respiratory tract infection in infants and young children worldwide. 29085762 5 65 theme NA1 846:848 arg1 genotype 850:857 NA1 genotype 846:857 NA1 genotype 846:857 The majority (57.4%, 159/277) of the RSV belonged to subgroup A (RSV-A), of which NA1 genotype was the most common in 2012 while ON1 genotype became prevalent the following year. 29085762 5 65 theme NA1 846:848 arg1 common 872:877 common 872:877 common 872:877 The majority (57.4%, 159/277) of the RSV belonged to subgroup A (RSV-A), of which NA1 genotype was the most common in 2012 while ON1 genotype became prevalent the following year. 29085762 0 66 from Thailand 73:80 arg1 prevalent 60:68 prevalent 60:68 prevalent 60:68 Respiratory syncytial virus genotypes NA1, ON1, and BA9 are prevalent in Thailand, 2012-2015. 29085762 6 67 theme 118/277 1010:1016 arg1 % 1007:1007 42.6% 1003:1007 42.6% 1003:1007 Among samples tested positive for RSV-B subgroup B (RSV-B) (42.6%, 118/277), most were genotype BA9 (92.6%, 87/94) with some BA10 and BA-C. 29085762 2 68 dep years 280:284 arg1 January 287:293 January 287:293 January 287:293 To investigate the RSV burden in Thailand over four consecutive years (January 2012 to December 2015), we screened 3,306 samples obtained from children ≤5 years old with acute respiratory tract infection using semi-nested reverse-transcription polymerase chain reaction (RT-PCR). 29085762 4 69 theme phylogenetic 701:712 arg1 analysis 714:721 phylogenetic analysis 701:721 phylogenetic analysis 701:721 We then genotyped RSV by sequencing the G glycoprotein gene and performed phylogenetic analysis to determine the RSV antigenic subgroup. 29085762 8 70 theme virus 1472:1476 arg1 circulation 1435:1445 the continued circulation 1421:1445 the continued circulation of this rapidly evolving virus 1421:1476 Positive selection of key residues combined with notable sequence variations on the G gene contributed to the continued circulation of this rapidly evolving virus. 29085762 6 71 dep B 992:992 arg1 % 1007:1007 42.6% 1003:1007 42.6% 1003:1007 Among samples tested positive for RSV-B subgroup B (RSV-B) (42.6%, 118/277), most were genotype BA9 (92.6%, 87/94) with some BA10 and BA-C. 29085762 6 72 dep BA9 1039:1041 arg1 87/94 1051:1055 87/94 1051:1055 87/94 1051:1055 Among samples tested positive for RSV-B subgroup B (RSV-B) (42.6%, 118/277), most were genotype BA9 (92.6%, 87/94) with some BA10 and BA-C. 29085762 6 72 dep BA9 1039:1041 arg1 % 1048:1048 92.6% 1044:1048 92.6% 1044:1048 Among samples tested positive for RSV-B subgroup B (RSV-B) (42.6%, 118/277), most were genotype BA9 (92.6%, 87/94) with some BA10 and BA-C. 29085762 8 73 theme G 1399:1399 arg1 gene 1401:1404 the G gene 1395:1404 the G gene 1395:1404 Positive selection of key residues combined with notable sequence variations on the G gene contributed to the continued circulation of this rapidly evolving virus. 29085762 1 74 theme worldwide 205:213 arg1 children 196:203 young children 190:203 young children worldwide 190:213 Respiratory syncytial virus (RSV) causes acute lower respiratory tract infection in infants and young children worldwide. 29085762 2 75 theme chain 471:475 arg1 RT-PCR 487:492 RT-PCR 487:492 RT-PCR 487:492 To investigate the RSV burden in Thailand over four consecutive years (January 2012 to December 2015), we screened 3,306 samples obtained from children ≤5 years old with acute respiratory tract infection using semi-nested reverse-transcription polymerase chain reaction (RT-PCR). 29085762 2 75 theme chain 471:475 arg1 reaction 477:484 semi-nested reverse-transcription polymerase chain reaction 426:484 semi-nested reverse-transcription polymerase chain reaction (RT-PCR) 426:493 To investigate the RSV burden in Thailand over four consecutive years (January 2012 to December 2015), we screened 3,306 samples obtained from children ≤5 years old with acute respiratory tract infection using semi-nested reverse-transcription polymerase chain reaction (RT-PCR). 29085762 8 76 theme key 1337:1339 arg1 residues 1341:1348 key residues 1337:1348 key residues combined with notable sequence variations on the G gene 1337:1404 Positive selection of key residues combined with notable sequence variations on the G gene contributed to the continued circulation of this rapidly evolving virus. 29085762 0 77 theme virus 22:26 arg1 genotypes 28:36 Respiratory syncytial virus genotypes 0:36 Respiratory syncytial virus genotypes NA1, ON1, and BA9 0:54 Respiratory syncytial virus genotypes NA1, ON1, and BA9 are prevalent in Thailand, 2012-2015. 29085762 0 77 theme virus 22:26 arg1 ON1 43:45 ON1 43:45 ON1 43:45 Respiratory syncytial virus genotypes NA1, ON1, and BA9 are prevalent in Thailand, 2012-2015. 29085762 0 77 theme virus 22:26 arg1 BA9 52:54 BA9 52:54 BA9 52:54 Respiratory syncytial virus genotypes NA1, ON1, and BA9 are prevalent in Thailand, 2012-2015. 29085762 0 77 theme virus 22:26 arg1 NA1 38:40 NA1 38:40 NA1 38:40 Respiratory syncytial virus genotypes NA1, ON1, and BA9 are prevalent in Thailand, 2012-2015. 29085762 0 78 theme syncytial 12:20 arg1 genotypes 28:36 Respiratory syncytial virus genotypes 0:36 Respiratory syncytial virus genotypes NA1, ON1, and BA9 0:54 Respiratory syncytial virus genotypes NA1, ON1, and BA9 are prevalent in Thailand, 2012-2015. 29085762 0 78 theme syncytial 12:20 arg1 ON1 43:45 ON1 43:45 ON1 43:45 Respiratory syncytial virus genotypes NA1, ON1, and BA9 are prevalent in Thailand, 2012-2015. 29085762 0 78 theme syncytial 12:20 arg1 BA9 52:54 BA9 52:54 BA9 52:54 Respiratory syncytial virus genotypes NA1, ON1, and BA9 are prevalent in Thailand, 2012-2015. 29085762 0 78 theme syncytial 12:20 arg1 NA1 38:40 NA1 38:40 NA1 38:40 Respiratory syncytial virus genotypes NA1, ON1, and BA9 are prevalent in Thailand, 2012-2015. 29085762 8 79 theme notable 1364:1370 arg1 variations 1381:1390 notable sequence variations 1364:1390 notable sequence variations on the G gene 1364:1404 Positive selection of key residues combined with notable sequence variations on the G gene contributed to the continued circulation of this rapidly evolving virus. 29085762 8 80 theme residues 1341:1348 arg1 selection 1324:1332 Positive selection 1315:1332 Positive selection of key residues combined with notable sequence variations on the G gene 1315:1404 Positive selection of key residues combined with notable sequence variations on the G gene contributed to the continued circulation of this rapidly evolving virus. 28916753 4 0 theme exoglycosidase 651:664 arg1 enzymes 666:672 the appropriate exoglycosidase enzymes 635:672 the appropriate exoglycosidase enzymes in conjunction with the utilization of some of the features of a capillary electrophoresis (CE) instrument to speed up the process 635:803 In this paper we introduce an automated carbohydrate sequencing approach using the appropriate exoglycosidase enzymes in conjunction with the utilization of some of the features of a capillary electrophoresis (CE) instrument to speed up the process. 28916753 1 1 link N-linked 119:126 arg1 carbohydrates 128:140 the N-linked carbohydrates 115:140 the N-linked carbohydrates of glycoproteins 115:157 Comprehensive analysis of the N-linked carbohydrates of glycoproteins is gaining high recent interest in both the biopharmaceutical and biomedical fields. 28916753 6 2 from 60 1160:1161 arg1 methods 1219:1225 the fully-automated methods 1199:1225 the fully-automated methods 1199:1225 CE analysis was conducted after each digestion step obtaining in this way the sequence information of N-glycans in 60 and 128 minutes using the semi- and the fully-automated methods, respectively. 28916753 6 2 from 60 1160:1161 arg1 information 1132:1142 the sequence information 1119:1142 the sequence information of N-glycans in 60 1119:1161 CE analysis was conducted after each digestion step obtaining in this way the sequence information of N-glycans in 60 and 128 minutes using the semi- and the fully-automated methods, respectively. 28916753 6 2 from 60 1160:1161 arg1 128 minutes 1167:1177 128 minutes 1167:1177 128 minutes using the semi- 1167:1193 CE analysis was conducted after each digestion step obtaining in this way the sequence information of N-glycans in 60 and 128 minutes using the semi- and the fully-automated methods, respectively. 28916753 2 3 theme carbohydrate 402:413 arg1 sequencing 415:424 carbohydrate sequencing 402:424 carbohydrate sequencing 402:424 In addition to high resolution glycosylation profiling, sugar residue and linkage specific enzymes are also routinely used for exoglycosidase digestion based carbohydrate sequencing. 28916753 4 4 theme appropriate 639:649 arg1 enzymes 666:672 the appropriate exoglycosidase enzymes 635:672 the appropriate exoglycosidase enzymes in conjunction with the utilization of some of the features of a capillary electrophoresis (CE) instrument to speed up the process 635:803 In this paper we introduce an automated carbohydrate sequencing approach using the appropriate exoglycosidase enzymes in conjunction with the utilization of some of the features of a capillary electrophoresis (CE) instrument to speed up the process. 28916753 3 5 dep practiced 488:496 arg1 introduced 451:460 introduced 451:460 introduced decades ago 451:472 This latter one, albeit introduced decades ago, still mostly practiced by following tedious and time consuming manual processes. 28916753 6 6 theme digestion 1082:1090 arg1 step 1092:1095 each digestion step 1077:1095 each digestion step 1077:1095 CE analysis was conducted after each digestion step obtaining in this way the sequence information of N-glycans in 60 and 128 minutes using the semi- and the fully-automated methods, respectively. 28916753 4 7 from enzymes 666:672 arg1 conjunction 677:687 conjunction 677:687 conjunction with the utilization of some of the features of a capillary electrophoresis (CE) instrument to speed up the process 677:803 In this paper we introduce an automated carbohydrate sequencing approach using the appropriate exoglycosidase enzymes in conjunction with the utilization of some of the features of a capillary electrophoresis (CE) instrument to speed up the process. 28916753 1 8 theme Comprehensive 89:101 arg1 analysis 103:110 Comprehensive analysis 89:110 Comprehensive analysis of the N-linked carbohydrates of glycoproteins 89:157 Comprehensive analysis of the N-linked carbohydrates of glycoproteins is gaining high recent interest in both the biopharmaceutical and biomedical fields. 28916753 6 9 from 128 minutes 1167:1177 arg1 60 1160:1161 60 1160:1161 60 1160:1161 CE analysis was conducted after each digestion step obtaining in this way the sequence information of N-glycans in 60 and 128 minutes using the semi- and the fully-automated methods, respectively. 28916753 2 10 theme specific 326:333 arg1 enzymes 335:341 linkage specific enzymes 318:341 linkage specific enzymes 318:341 In addition to high resolution glycosylation profiling, sugar residue and linkage specific enzymes are also routinely used for exoglycosidase digestion based carbohydrate sequencing. 28916753 3 11 theme manual 538:543 arg1 processes 545:553 tedious and time consuming manual processes 511:553 tedious and time consuming manual processes 511:553 This latter one, albeit introduced decades ago, still mostly practiced by following tedious and time consuming manual processes. 28916753 5 12 theme accurate 996:1003 arg1 delivery 1005:1012 accurate delivery 996:1012 accurate delivery of the exoglycosidase enzymes 996:1042 The enzymatic reactions were accomplished within the temperature controlled sample storage compartment of a capillary electrophoresis unit and the separation capillary was also utilized for accurate delivery of the exoglycosidase enzymes. 28916753 5 13 theme sample 882:887 arg1 compartment 897:907 the temperature controlled sample storage compartment 855:907 the temperature controlled sample storage compartment of a capillary electrophoresis unit 855:943 The enzymatic reactions were accomplished within the temperature controlled sample storage compartment of a capillary electrophoresis unit and the separation capillary was also utilized for accurate delivery of the exoglycosidase enzymes. 28916753 2 14 theme linkage 318:324 arg1 enzymes 335:341 linkage specific enzymes 318:341 linkage specific enzymes 318:341 In addition to high resolution glycosylation profiling, sugar residue and linkage specific enzymes are also routinely used for exoglycosidase digestion based carbohydrate sequencing. 28916753 5 15 theme separation 953:962 arg1 capillary 964:972 the separation capillary 949:972 the separation capillary 949:972 The enzymatic reactions were accomplished within the temperature controlled sample storage compartment of a capillary electrophoresis unit and the separation capillary was also utilized for accurate delivery of the exoglycosidase enzymes. 28916753 5 16 theme controlled 871:880 arg1 compartment 897:907 the temperature controlled sample storage compartment 855:907 the temperature controlled sample storage compartment of a capillary electrophoresis unit 855:943 The enzymatic reactions were accomplished within the temperature controlled sample storage compartment of a capillary electrophoresis unit and the separation capillary was also utilized for accurate delivery of the exoglycosidase enzymes. 28916753 6 17 theme fully-automated 1203:1217 arg1 methods 1219:1225 the fully-automated methods 1199:1225 the fully-automated methods 1199:1225 CE analysis was conducted after each digestion step obtaining in this way the sequence information of N-glycans in 60 and 128 minutes using the semi- and the fully-automated methods, respectively. 28916753 6 18 from information 1132:1142 arg1 60 1160:1161 60 1160:1161 60 1160:1161 CE analysis was conducted after each digestion step obtaining in this way the sequence information of N-glycans in 60 and 128 minutes using the semi- and the fully-automated methods, respectively. 28916753 5 19 theme storage 889:895 arg1 compartment 897:907 the temperature controlled sample storage compartment 855:907 the temperature controlled sample storage compartment of a capillary electrophoresis unit 855:943 The enzymatic reactions were accomplished within the temperature controlled sample storage compartment of a capillary electrophoresis unit and the separation capillary was also utilized for accurate delivery of the exoglycosidase enzymes. 28916753 1 20 theme biopharmaceutical 203:219 arg1 fields 236:241 both the biopharmaceutical and biomedical fields 194:241 fields 236:241 Comprehensive analysis of the N-linked carbohydrates of glycoproteins is gaining high recent interest in both the biopharmaceutical and biomedical fields. 28916753 0 21 theme N-Glycosylation 10:24 arg1 Sequencing 26:35 Automated N-Glycosylation Sequencing 0:35 Automated N-Glycosylation Sequencing Of Biopharmaceuticals By Capillary Electrophoresis 0:86 Automated N-Glycosylation Sequencing Of Biopharmaceuticals By Capillary Electrophoresis. 28916753 5 22 theme exoglycosidase 1021:1034 arg1 enzymes 1036:1042 the exoglycosidase enzymes 1017:1042 the exoglycosidase enzymes 1017:1042 The enzymatic reactions were accomplished within the temperature controlled sample storage compartment of a capillary electrophoresis unit and the separation capillary was also utilized for accurate delivery of the exoglycosidase enzymes. 28916753 4 23 theme capillary 739:747 arg1 CE 766:767 CE 766:767 CE 766:767 In this paper we introduce an automated carbohydrate sequencing approach using the appropriate exoglycosidase enzymes in conjunction with the utilization of some of the features of a capillary electrophoresis (CE) instrument to speed up the process. 28916753 4 23 theme capillary 739:747 arg1 electrophoresis 749:763 a capillary electrophoresis 737:763 a capillary electrophoresis (CE) instrument to speed up the process 737:803 In this paper we introduce an automated carbohydrate sequencing approach using the appropriate exoglycosidase enzymes in conjunction with the utilization of some of the features of a capillary electrophoresis (CE) instrument to speed up the process. 28916753 0 24 theme Automated 0:8 arg1 Sequencing 26:35 Automated N-Glycosylation Sequencing 0:35 Automated N-Glycosylation Sequencing Of Biopharmaceuticals By Capillary Electrophoresis 0:86 Automated N-Glycosylation Sequencing Of Biopharmaceuticals By Capillary Electrophoresis. 28916753 6 25 from N-glycans 1147:1155 arg1 60 1160:1161 60 1160:1161 60 1160:1161 CE analysis was conducted after each digestion step obtaining in this way the sequence information of N-glycans in 60 and 128 minutes using the semi- and the fully-automated methods, respectively. 28916753 1 26 theme N-linked 119:126 arg1 carbohydrates 128:140 the N-linked carbohydrates 115:140 the N-linked carbohydrates of glycoproteins 115:157 Comprehensive analysis of the N-linked carbohydrates of glycoproteins is gaining high recent interest in both the biopharmaceutical and biomedical fields. 28916753 1 27 theme biomedical 225:234 arg1 fields 236:241 both the biopharmaceutical and biomedical fields 194:241 fields 236:241 Comprehensive analysis of the N-linked carbohydrates of glycoproteins is gaining high recent interest in both the biopharmaceutical and biomedical fields. 28916753 4 28 theme sequencing 609:618 arg1 approach 620:627 an automated carbohydrate sequencing approach 583:627 an automated carbohydrate sequencing approach using the appropriate exoglycosidase enzymes in conjunction with the utilization of some of the features of a capillary electrophoresis (CE) instrument to speed up the process 583:803 In this paper we introduce an automated carbohydrate sequencing approach using the appropriate exoglycosidase enzymes in conjunction with the utilization of some of the features of a capillary electrophoresis (CE) instrument to speed up the process. 28916753 1 29 theme carbohydrates 128:140 arg1 analysis 103:110 Comprehensive analysis 89:110 Comprehensive analysis of the N-linked carbohydrates of glycoproteins 89:157 Comprehensive analysis of the N-linked carbohydrates of glycoproteins is gaining high recent interest in both the biopharmaceutical and biomedical fields. 28916753 4 30 theme some 713:716 arg1 utilization 698:708 the utilization 694:708 the utilization of some of the features of a capillary electrophoresis (CE) instrument to speed up the process 694:803 In this paper we introduce an automated carbohydrate sequencing approach using the appropriate exoglycosidase enzymes in conjunction with the utilization of some of the features of a capillary electrophoresis (CE) instrument to speed up the process. 28916753 5 31 theme enzymes 1036:1042 arg1 delivery 1005:1012 accurate delivery 996:1012 accurate delivery of the exoglycosidase enzymes 996:1042 The enzymatic reactions were accomplished within the temperature controlled sample storage compartment of a capillary electrophoresis unit and the separation capillary was also utilized for accurate delivery of the exoglycosidase enzymes. 28916753 1 32 gly glycoproteins 145:157 arg1 glycoproteins 145:157 glycoproteins 145:157 glycoproteins 145:157 Comprehensive analysis of the N-linked carbohydrates of glycoproteins is gaining high recent interest in both the biopharmaceutical and biomedical fields. 28916753 5 33 theme capillary 914:922 arg1 unit 940:943 a capillary electrophoresis unit 912:943 a capillary electrophoresis unit 912:943 The enzymatic reactions were accomplished within the temperature controlled sample storage compartment of a capillary electrophoresis unit and the separation capillary was also utilized for accurate delivery of the exoglycosidase enzymes. 28916753 2 34 theme glycosylation 275:287 arg1 profiling 289:297 glycosylation profiling 275:297 glycosylation profiling 275:297 In addition to high resolution glycosylation profiling, sugar residue and linkage specific enzymes are also routinely used for exoglycosidase digestion based carbohydrate sequencing. 28916753 5 35 theme electrophoresis 924:938 arg1 unit 940:943 a capillary electrophoresis unit 912:943 a capillary electrophoresis unit 912:943 The enzymatic reactions were accomplished within the temperature controlled sample storage compartment of a capillary electrophoresis unit and the separation capillary was also utilized for accurate delivery of the exoglycosidase enzymes. 28916753 0 36 theme Biopharmaceuticals 40:57 arg1 Sequencing 26:35 Automated N-Glycosylation Sequencing 0:35 Automated N-Glycosylation Sequencing Of Biopharmaceuticals By Capillary Electrophoresis 0:86 Automated N-Glycosylation Sequencing Of Biopharmaceuticals By Capillary Electrophoresis. 28916753 6 37 theme CE 1045:1046 arg1 analysis 1048:1055 CE analysis 1045:1055 CE analysis 1045:1055 CE analysis was conducted after each digestion step obtaining in this way the sequence information of N-glycans in 60 and 128 minutes using the semi- and the fully-automated methods, respectively. 28916753 5 38 used utilized 983:990 arg2 capillary 964:972 the separation capillary 949:972 the separation capillary 949:972 The enzymatic reactions were accomplished within the temperature controlled sample storage compartment of a capillary electrophoresis unit and the separation capillary was also utilized for accurate delivery of the exoglycosidase enzymes. 28916753 5 39 theme unit 940:943 arg1 compartment 897:907 the temperature controlled sample storage compartment 855:907 the temperature controlled sample storage compartment of a capillary electrophoresis unit 855:943 The enzymatic reactions were accomplished within the temperature controlled sample storage compartment of a capillary electrophoresis unit and the separation capillary was also utilized for accurate delivery of the exoglycosidase enzymes. 28916753 2 40 dep resolution 264:273 arg1 addition 247:254 addition 247:254 addition 247:254 In addition to high resolution glycosylation profiling, sugar residue and linkage specific enzymes are also routinely used for exoglycosidase digestion based carbohydrate sequencing. 28916753 6 41 theme sequence 1123:1130 arg1 information 1132:1142 the sequence information 1119:1142 the sequence information of N-glycans in 60 1119:1161 CE analysis was conducted after each digestion step obtaining in this way the sequence information of N-glycans in 60 and 128 minutes using the semi- and the fully-automated methods, respectively. 28916753 2 42 theme high 259:262 arg1 resolution 264:273 high resolution 259:273 high resolution 259:273 In addition to high resolution glycosylation profiling, sugar residue and linkage specific enzymes are also routinely used for exoglycosidase digestion based carbohydrate sequencing. 28916753 1 43 theme glycoproteins 145:157 arg1 carbohydrates 128:140 the N-linked carbohydrates 115:140 the N-linked carbohydrates of glycoproteins 115:157 Comprehensive analysis of the N-linked carbohydrates of glycoproteins is gaining high recent interest in both the biopharmaceutical and biomedical fields. 28916753 0 44 theme Capillary 62:70 arg1 Electrophoresis 72:86 Capillary Electrophoresis 62:86 Capillary Electrophoresis 62:86 Automated N-Glycosylation Sequencing Of Biopharmaceuticals By Capillary Electrophoresis. 28916753 4 45 theme carbohydrate 596:607 arg1 approach 620:627 an automated carbohydrate sequencing approach 583:627 an automated carbohydrate sequencing approach using the appropriate exoglycosidase enzymes in conjunction with the utilization of some of the features of a capillary electrophoresis (CE) instrument to speed up the process 583:803 In this paper we introduce an automated carbohydrate sequencing approach using the appropriate exoglycosidase enzymes in conjunction with the utilization of some of the features of a capillary electrophoresis (CE) instrument to speed up the process. 28916753 4 46 with conjunction 677:687 arg1 utilization 698:708 the utilization 694:708 the utilization of some of the features of a capillary electrophoresis (CE) instrument to speed up the process 694:803 In this paper we introduce an automated carbohydrate sequencing approach using the appropriate exoglycosidase enzymes in conjunction with the utilization of some of the features of a capillary electrophoresis (CE) instrument to speed up the process. 28916753 4 47 theme instrument 770:779 arg1 features 725:732 the features 721:732 the features of a capillary electrophoresis (CE) instrument to speed up the process 721:803 In this paper we introduce an automated carbohydrate sequencing approach using the appropriate exoglycosidase enzymes in conjunction with the utilization of some of the features of a capillary electrophoresis (CE) instrument to speed up the process. 28916753 4 48 theme automated 586:594 arg1 approach 620:627 an automated carbohydrate sequencing approach 583:627 an automated carbohydrate sequencing approach using the appropriate exoglycosidase enzymes in conjunction with the utilization of some of the features of a capillary electrophoresis (CE) instrument to speed up the process 583:803 In this paper we introduce an automated carbohydrate sequencing approach using the appropriate exoglycosidase enzymes in conjunction with the utilization of some of the features of a capillary electrophoresis (CE) instrument to speed up the process. 28916753 6 49 from methods 1219:1225 arg1 60 1160:1161 60 1160:1161 60 1160:1161 CE analysis was conducted after each digestion step obtaining in this way the sequence information of N-glycans in 60 and 128 minutes using the semi- and the fully-automated methods, respectively. 28916753 2 50 theme exoglycosidase 371:384 arg1 digestion 386:394 exoglycosidase digestion 371:394 exoglycosidase digestion based carbohydrate sequencing 371:424 In addition to high resolution glycosylation profiling, sugar residue and linkage specific enzymes are also routinely used for exoglycosidase digestion based carbohydrate sequencing. 28916753 2 51 theme sugar 300:304 arg1 residue 306:312 sugar residue 300:312 sugar residue 300:312 In addition to high resolution glycosylation profiling, sugar residue and linkage specific enzymes are also routinely used for exoglycosidase digestion based carbohydrate sequencing. 28916753 1 52 theme high 170:173 arg1 interest 182:189 high recent interest 170:189 high recent interest 170:189 Comprehensive analysis of the N-linked carbohydrates of glycoproteins is gaining high recent interest in both the biopharmaceutical and biomedical fields. 28916753 3 53 theme consuming 528:536 arg1 processes 545:553 tedious and time consuming manual processes 511:553 tedious and time consuming manual processes 511:553 This latter one, albeit introduced decades ago, still mostly practiced by following tedious and time consuming manual processes. 28916753 5 54 theme enzymatic 810:818 arg1 reactions 820:828 The enzymatic reactions 806:828 The enzymatic reactions 806:828 The enzymatic reactions were accomplished within the temperature controlled sample storage compartment of a capillary electrophoresis unit and the separation capillary was also utilized for accurate delivery of the exoglycosidase enzymes. 28916753 3 55 theme tedious 511:517 arg1 processes 545:553 tedious and time consuming manual processes 511:553 tedious and time consuming manual processes 511:553 This latter one, albeit introduced decades ago, still mostly practiced by following tedious and time consuming manual processes. 28916753 1 56 dep fields 236:241 arg1 both 194:197 both 194:197 both 194:197 Comprehensive analysis of the N-linked carbohydrates of glycoproteins is gaining high recent interest in both the biopharmaceutical and biomedical fields. 28916753 6 57 theme N-glycans 1147:1155 arg1 methods 1219:1225 the fully-automated methods 1199:1225 the fully-automated methods 1199:1225 CE analysis was conducted after each digestion step obtaining in this way the sequence information of N-glycans in 60 and 128 minutes using the semi- and the fully-automated methods, respectively. 28916753 6 57 theme N-glycans 1147:1155 arg1 information 1132:1142 the sequence information 1119:1142 the sequence information of N-glycans in 60 1119:1161 CE analysis was conducted after each digestion step obtaining in this way the sequence information of N-glycans in 60 and 128 minutes using the semi- and the fully-automated methods, respectively. 28916753 6 57 theme N-glycans 1147:1155 arg1 128 minutes 1167:1177 128 minutes 1167:1177 128 minutes using the semi- 1167:1193 CE analysis was conducted after each digestion step obtaining in this way the sequence information of N-glycans in 60 and 128 minutes using the semi- and the fully-automated methods, respectively. 28916753 1 58 theme recent 175:180 arg1 interest 182:189 high recent interest 170:189 high recent interest 170:189 Comprehensive analysis of the N-linked carbohydrates of glycoproteins is gaining high recent interest in both the biopharmaceutical and biomedical fields. 28916753 2 59 used used 362:365 arg2 residue 306:312 sugar residue 300:312 sugar residue 300:312 In addition to high resolution glycosylation profiling, sugar residue and linkage specific enzymes are also routinely used for exoglycosidase digestion based carbohydrate sequencing. 28916753 2 59 used used 362:365 arg2 enzymes 335:341 linkage specific enzymes 318:341 linkage specific enzymes 318:341 In addition to high resolution glycosylation profiling, sugar residue and linkage specific enzymes are also routinely used for exoglycosidase digestion based carbohydrate sequencing. 28916753 2 59 used used 362:365 arg2 profiling 289:297 glycosylation profiling 275:297 glycosylation profiling 275:297 In addition to high resolution glycosylation profiling, sugar residue and linkage specific enzymes are also routinely used for exoglycosidase digestion based carbohydrate sequencing. 28916753 4 60 theme electrophoresis 749:763 arg1 instrument 770:779 a capillary electrophoresis (CE) instrument 737:779 a capillary electrophoresis (CE) instrument to speed up the process 737:803 In this paper we introduce an automated carbohydrate sequencing approach using the appropriate exoglycosidase enzymes in conjunction with the utilization of some of the features of a capillary electrophoresis (CE) instrument to speed up the process. 28069378 1 0 theme Guillain-Barré 324:337 arg1 syndrome 339:346 Guillain-Barré syndrome 324:346 Guillain-Barré syndrome 324:346 Zika virus has rapidly spread reaching a global distribution pattern similar to that of dengue virus, and has been associated with serious neurological and developmental pathologies, like congenital malformation during pregnancy and Guillain-Barré syndrome. 28069378 6 1 theme Nile 1063:1066 arg1 virus 1068:1072 a West Nile virus 1056:1072 a West Nile virus replicon packaged with the Zika virus structural proteins C-PrM-E 1056:1138 Production of pseudoviral particles with a West Nile virus replicon packaged with the Zika virus structural proteins C-PrM-E was significantly reduced with the non-glycosylated E. Similarly, glycosylation-negative pseudoviral particles showed impaired infectivity of Vero cells and reduced ability to infect K562 cells upon particles opsonisation with anti-E antibodies. 28069378 6 2 theme particles 1041:1049 arg1 Production 1015:1024 Production 1015:1024 Production of pseudoviral particles with a West Nile virus replicon packaged with the Zika virus structural proteins C-PrM-E 1015:1138 Production of pseudoviral particles with a West Nile virus replicon packaged with the Zika virus structural proteins C-PrM-E was significantly reduced with the non-glycosylated E. Similarly, glycosylation-negative pseudoviral particles showed impaired infectivity of Vero cells and reduced ability to infect K562 cells upon particles opsonisation with anti-E antibodies. 28069378 1 3 theme global 132:137 arg1 pattern 152:158 a global distribution pattern 130:158 a global distribution pattern similar to that of dengue virus 130:190 Zika virus has rapidly spread reaching a global distribution pattern similar to that of dengue virus, and has been associated with serious neurological and developmental pathologies, like congenital malformation during pregnancy and Guillain-Barré syndrome. 28069378 0 4 theme viral 59:63 arg1 secretion 48:56 Zika virus E protein secretion 27:56 Zika virus E protein secretion 27:56 Role of N-glycosylation on Zika virus E protein secretion, viral assembly and infectivity. 28069378 0 4 theme viral 59:63 arg1 assembly 65:72 viral assembly 59:72 viral assembly 59:72 Role of N-glycosylation on Zika virus E protein secretion, viral assembly and infectivity. 28069378 3 5 theme mammalian 672:680 arg1 cells 682:686 mammalian cells 672:686 mammalian cells 672:686 We found that loss of E N-linked glycosylation leads to compromised expression and secretion of E ectodomain from mammalian cells. 28069378 1 6 theme distribution 139:150 arg1 pattern 152:158 a global distribution pattern 130:158 a global distribution pattern similar to that of dengue virus 130:190 Zika virus has rapidly spread reaching a global distribution pattern similar to that of dengue virus, and has been associated with serious neurological and developmental pathologies, like congenital malformation during pregnancy and Guillain-Barré syndrome. 28069378 1 7 theme serious 222:228 arg1 pathologies 261:271 serious neurological and developmental pathologies 222:271 serious neurological and developmental pathologies 222:271 Zika virus has rapidly spread reaching a global distribution pattern similar to that of dengue virus, and has been associated with serious neurological and developmental pathologies, like congenital malformation during pregnancy and Guillain-Barré syndrome. 28069378 0 8 from Role 0:3 arg1 infectivity 78:88 infectivity 78:88 infectivity 78:88 Role of N-glycosylation on Zika virus E protein secretion, viral assembly and infectivity. 28069378 0 8 from Role 0:3 arg1 secretion 48:56 Zika virus E protein secretion 27:56 Zika virus E protein secretion 27:56 Role of N-glycosylation on Zika virus E protein secretion, viral assembly and infectivity. 28069378 0 8 from Role 0:3 arg1 assembly 65:72 viral assembly 59:72 viral assembly 59:72 Role of N-glycosylation on Zika virus E protein secretion, viral assembly and infectivity. 28069378 2 9 theme Sequence 349:356 arg1 analysis 358:365 Sequence analysis 349:365 Sequence analysis of different clinical and laboratory isolates 349:411 Sequence analysis of different clinical and laboratory isolates has shown the existence of mutants with loss of the conserved N-glycosylation motif on domain I of protein E that is common to all flaviviruses. 28069378 5 10 theme impaired 948:955 arg1 secretion 957:965 impaired secretion 948:965 impaired secretion 948:965 Low temperature (28 °C) favoured secretion, although the glycosylation mutant E ectodomain showed impaired secretion and membrane display compared to the wild type. 28069378 1 11 theme neurological 230:241 arg1 pathologies 261:271 serious neurological and developmental pathologies 222:271 serious neurological and developmental pathologies 222:271 Zika virus has rapidly spread reaching a global distribution pattern similar to that of dengue virus, and has been associated with serious neurological and developmental pathologies, like congenital malformation during pregnancy and Guillain-Barré syndrome. 28069378 2 12 theme E 520:520 arg1 domain 500:505 domain I 500:507 domain I of protein E that is common to all flaviviruses 500:555 Sequence analysis of different clinical and laboratory isolates has shown the existence of mutants with loss of the conserved N-glycosylation motif on domain I of protein E that is common to all flaviviruses. 28069378 2 12 theme E 520:520 arg1 E 520:520 protein E 512:520 protein E that is common to all flaviviruses 512:555 Sequence analysis of different clinical and laboratory isolates has shown the existence of mutants with loss of the conserved N-glycosylation motif on domain I of protein E that is common to all flaviviruses. 28069378 6 13 theme glycosylation-negative 1206:1227 arg1 particles 1241:1249 glycosylation-negative pseudoviral particles 1206:1249 glycosylation-negative pseudoviral particles 1206:1249 Production of pseudoviral particles with a West Nile virus replicon packaged with the Zika virus structural proteins C-PrM-E was significantly reduced with the non-glycosylated E. Similarly, glycosylation-negative pseudoviral particles showed impaired infectivity of Vero cells and reduced ability to infect K562 cells upon particles opsonisation with anti-E antibodies. 28069378 6 14 theme reduced 1297:1303 arg1 ability 1305:1311 reduced ability 1297:1311 reduced ability to infect K562 cells upon particles opsonisation with anti-E antibodies 1297:1383 Production of pseudoviral particles with a West Nile virus replicon packaged with the Zika virus structural proteins C-PrM-E was significantly reduced with the non-glycosylated E. Similarly, glycosylation-negative pseudoviral particles showed impaired infectivity of Vero cells and reduced ability to infect K562 cells upon particles opsonisation with anti-E antibodies. 28069378 5 15 theme glycosylation 907:919 arg1 ectodomain 930:939 the glycosylation mutant E ectodomain 903:939 the glycosylation mutant E ectodomain 903:939 Low temperature (28 °C) favoured secretion, although the glycosylation mutant E ectodomain showed impaired secretion and membrane display compared to the wild type. 28069378 2 16 theme protein 512:518 arg1 E 520:520 protein E 512:520 protein E that is common to all flaviviruses 512:555 Sequence analysis of different clinical and laboratory isolates has shown the existence of mutants with loss of the conserved N-glycosylation motif on domain I of protein E that is common to all flaviviruses. 28069378 5 17 theme Low 850:852 arg1 28 °C 867:871 28 °C 867:871 28 °C 867:871 Low temperature (28 °C) favoured secretion, although the glycosylation mutant E ectodomain showed impaired secretion and membrane display compared to the wild type. 28069378 5 17 theme Low 850:852 arg1 temperature 854:864 Low temperature 850:864 Low temperature (28 °C) 850:872 Low temperature (28 °C) favoured secretion, although the glycosylation mutant E ectodomain showed impaired secretion and membrane display compared to the wild type. 28069378 2 18 theme isolates 404:411 arg1 analysis 358:365 Sequence analysis 349:365 Sequence analysis of different clinical and laboratory isolates 349:411 Sequence analysis of different clinical and laboratory isolates has shown the existence of mutants with loss of the conserved N-glycosylation motif on domain I of protein E that is common to all flaviviruses. 28069378 3 19 from secretion 641:649 arg1 cells 682:686 mammalian cells 672:686 mammalian cells 672:686 We found that loss of E N-linked glycosylation leads to compromised expression and secretion of E ectodomain from mammalian cells. 28069378 2 20 theme N-glycosylation 475:489 arg1 motif 491:495 the conserved N-glycosylation motif 461:495 the conserved N-glycosylation motif 461:495 Sequence analysis of different clinical and laboratory isolates has shown the existence of mutants with loss of the conserved N-glycosylation motif on domain I of protein E that is common to all flaviviruses. 28069378 5 21 theme membrane 971:978 arg1 display 980:986 membrane display 971:986 membrane display 971:986 Low temperature (28 °C) favoured secretion, although the glycosylation mutant E ectodomain showed impaired secretion and membrane display compared to the wild type. 28069378 1 22 theme similar 160:166 arg1 pattern 152:158 a global distribution pattern 130:158 a global distribution pattern similar to that of dengue virus 130:190 Zika virus has rapidly spread reaching a global distribution pattern similar to that of dengue virus, and has been associated with serious neurological and developmental pathologies, like congenital malformation during pregnancy and Guillain-Barré syndrome. 28069378 3 23 link N-linked 582:589 arg1 glycosylation 591:603 E N-linked glycosylation 580:603 E N-linked glycosylation 580:603 We found that loss of E N-linked glycosylation leads to compromised expression and secretion of E ectodomain from mammalian cells. 28069378 2 24 theme motif 491:495 arg1 loss 453:456 loss 453:456 loss of the conserved N-glycosylation motif 453:495 Sequence analysis of different clinical and laboratory isolates has shown the existence of mutants with loss of the conserved N-glycosylation motif on domain I of protein E that is common to all flaviviruses. 28069378 6 25 theme Vero 1282:1285 arg1 cells 1287:1291 Vero cells 1282:1291 Vero cells 1282:1291 Production of pseudoviral particles with a West Nile virus replicon packaged with the Zika virus structural proteins C-PrM-E was significantly reduced with the non-glycosylated E. Similarly, glycosylation-negative pseudoviral particles showed impaired infectivity of Vero cells and reduced ability to infect K562 cells upon particles opsonisation with anti-E antibodies. 28069378 6 26 dep proteins 1123:1130 arg1 C-PrM-E 1132:1138 C-PrM-E 1132:1138 C-PrM-E 1132:1138 Production of pseudoviral particles with a West Nile virus replicon packaged with the Zika virus structural proteins C-PrM-E was significantly reduced with the non-glycosylated E. Similarly, glycosylation-negative pseudoviral particles showed impaired infectivity of Vero cells and reduced ability to infect K562 cells upon particles opsonisation with anti-E antibodies. 28069378 4 27 theme glycosylation-negative 713:734 arg1 mutant 736:741 glycosylation-negative mutant 713:741 glycosylation-negative mutant 713:741 For both, wild type and glycosylation-negative mutant, secretion was independent of co-expression of the PrM viral protein, but highly dependent on temperature. 28069378 6 28 theme West 1058:1061 arg1 virus 1068:1072 a West Nile virus 1056:1072 a West Nile virus replicon packaged with the Zika virus structural proteins C-PrM-E 1056:1138 Production of pseudoviral particles with a West Nile virus replicon packaged with the Zika virus structural proteins C-PrM-E was significantly reduced with the non-glycosylated E. Similarly, glycosylation-negative pseudoviral particles showed impaired infectivity of Vero cells and reduced ability to infect K562 cells upon particles opsonisation with anti-E antibodies. 28069378 1 29 theme developmental 247:259 arg1 pathologies 261:271 serious neurological and developmental pathologies 222:271 serious neurological and developmental pathologies 222:271 Zika virus has rapidly spread reaching a global distribution pattern similar to that of dengue virus, and has been associated with serious neurological and developmental pathologies, like congenital malformation during pregnancy and Guillain-Barré syndrome. 28069378 6 30 with particles 1041:1049 arg1 replicon 1074:1081 a West Nile virus replicon 1056:1081 a West Nile virus replicon packaged with the Zika virus structural proteins C-PrM-E 1056:1138 Production of pseudoviral particles with a West Nile virus replicon packaged with the Zika virus structural proteins C-PrM-E was significantly reduced with the non-glycosylated E. Similarly, glycosylation-negative pseudoviral particles showed impaired infectivity of Vero cells and reduced ability to infect K562 cells upon particles opsonisation with anti-E antibodies. 28069378 5 31 theme E 928:928 arg1 ectodomain 930:939 the glycosylation mutant E ectodomain 903:939 the glycosylation mutant E ectodomain 903:939 Low temperature (28 °C) favoured secretion, although the glycosylation mutant E ectodomain showed impaired secretion and membrane display compared to the wild type. 28069378 6 32 theme virus 1068:1072 arg1 replicon 1074:1081 a West Nile virus replicon 1056:1081 a West Nile virus replicon packaged with the Zika virus structural proteins C-PrM-E 1056:1138 Production of pseudoviral particles with a West Nile virus replicon packaged with the Zika virus structural proteins C-PrM-E was significantly reduced with the non-glycosylated E. Similarly, glycosylation-negative pseudoviral particles showed impaired infectivity of Vero cells and reduced ability to infect K562 cells upon particles opsonisation with anti-E antibodies. 28069378 2 33 theme clinical 380:387 arg1 isolates 404:411 different clinical and laboratory isolates 370:411 different clinical and laboratory isolates 370:411 Sequence analysis of different clinical and laboratory isolates has shown the existence of mutants with loss of the conserved N-glycosylation motif on domain I of protein E that is common to all flaviviruses. 28069378 2 34 theme mutants 440:446 arg1 existence 427:435 the existence 423:435 the existence of mutants with loss of the conserved N-glycosylation motif on domain I of protein E that is common to all flaviviruses 423:555 Sequence analysis of different clinical and laboratory isolates has shown the existence of mutants with loss of the conserved N-glycosylation motif on domain I of protein E that is common to all flaviviruses. 28069378 4 35 theme PrM 794:796 arg1 protein 804:810 the PrM viral protein 790:810 the PrM viral protein 790:810 For both, wild type and glycosylation-negative mutant, secretion was independent of co-expression of the PrM viral protein, but highly dependent on temperature. 28069378 5 36 theme wild 1004:1007 arg1 type 1009:1012 the wild type 1000:1012 the wild type 1000:1012 Low temperature (28 °C) favoured secretion, although the glycosylation mutant E ectodomain showed impaired secretion and membrane display compared to the wild type. 28069378 0 37 theme N-glycosylation 8:22 arg1 Role 0:3 Role 0:3 Role of N-glycosylation on Zika virus E protein secretion, viral assembly and infectivity. 0:89 Role of N-glycosylation on Zika virus E protein secretion, viral assembly and infectivity. 28069378 1 38 theme Zika 91:94 arg1 virus 96:100 Zika virus 91:100 Zika virus 91:100 Zika virus has rapidly spread reaching a global distribution pattern similar to that of dengue virus, and has been associated with serious neurological and developmental pathologies, like congenital malformation during pregnancy and Guillain-Barré syndrome. 28069378 6 39 with opsonisation 1349:1360 arg1 antibodies 1374:1383 anti-E antibodies 1367:1383 anti-E antibodies 1367:1383 Production of pseudoviral particles with a West Nile virus replicon packaged with the Zika virus structural proteins C-PrM-E was significantly reduced with the non-glycosylated E. Similarly, glycosylation-negative pseudoviral particles showed impaired infectivity of Vero cells and reduced ability to infect K562 cells upon particles opsonisation with anti-E antibodies. 28069378 1 40 theme dengue 179:184 arg1 virus 186:190 dengue virus 179:190 dengue virus 179:190 Zika virus has rapidly spread reaching a global distribution pattern similar to that of dengue virus, and has been associated with serious neurological and developmental pathologies, like congenital malformation during pregnancy and Guillain-Barré syndrome. 28069378 0 41 theme virus 32:36 arg1 infectivity 78:88 infectivity 78:88 infectivity 78:88 Role of N-glycosylation on Zika virus E protein secretion, viral assembly and infectivity. 28069378 0 41 theme virus 32:36 arg1 secretion 48:56 Zika virus E protein secretion 27:56 Zika virus E protein secretion 27:56 Role of N-glycosylation on Zika virus E protein secretion, viral assembly and infectivity. 28069378 0 41 theme virus 32:36 arg1 assembly 65:72 viral assembly 59:72 viral assembly 59:72 Role of N-glycosylation on Zika virus E protein secretion, viral assembly and infectivity. 28069378 3 42 from cells 682:686 arg1 secretion 641:649 secretion 641:649 secretion 641:649 We found that loss of E N-linked glycosylation leads to compromised expression and secretion of E ectodomain from mammalian cells. 28069378 3 42 from cells 682:686 arg1 ectodomain 656:665 E ectodomain 654:665 E ectodomain from mammalian cells 654:686 We found that loss of E N-linked glycosylation leads to compromised expression and secretion of E ectodomain from mammalian cells. 28069378 3 42 from cells 682:686 arg1 expression 626:635 expression 626:635 expression 626:635 We found that loss of E N-linked glycosylation leads to compromised expression and secretion of E ectodomain from mammalian cells. 28069378 4 43 theme protein 804:810 arg1 co-expression 773:785 co-expression 773:785 co-expression of the PrM viral protein 773:810 For both, wild type and glycosylation-negative mutant, secretion was independent of co-expression of the PrM viral protein, but highly dependent on temperature. 28069378 6 44 theme pseudoviral 1029:1039 arg1 particles 1041:1049 pseudoviral particles 1029:1049 pseudoviral particles with a West Nile virus replicon packaged with the Zika virus structural proteins C-PrM-E 1029:1138 Production of pseudoviral particles with a West Nile virus replicon packaged with the Zika virus structural proteins C-PrM-E was significantly reduced with the non-glycosylated E. Similarly, glycosylation-negative pseudoviral particles showed impaired infectivity of Vero cells and reduced ability to infect K562 cells upon particles opsonisation with anti-E antibodies. 28069378 0 45 theme Zika 27:30 arg1 infectivity 78:88 infectivity 78:88 infectivity 78:88 Role of N-glycosylation on Zika virus E protein secretion, viral assembly and infectivity. 28069378 0 45 theme Zika 27:30 arg1 secretion 48:56 Zika virus E protein secretion 27:56 Zika virus E protein secretion 27:56 Role of N-glycosylation on Zika virus E protein secretion, viral assembly and infectivity. 28069378 0 45 theme Zika 27:30 arg1 assembly 65:72 viral assembly 59:72 viral assembly 59:72 Role of N-glycosylation on Zika virus E protein secretion, viral assembly and infectivity. 28069378 1 46 theme congenital 279:288 arg1 malformation 290:301 congenital malformation 279:301 congenital malformation during pregnancy and Guillain-Barré syndrome 279:346 Zika virus has rapidly spread reaching a global distribution pattern similar to that of dengue virus, and has been associated with serious neurological and developmental pathologies, like congenital malformation during pregnancy and Guillain-Barré syndrome. 28069378 2 47 theme conserved 465:473 arg1 motif 491:495 the conserved N-glycosylation motif 461:495 the conserved N-glycosylation motif 461:495 Sequence analysis of different clinical and laboratory isolates has shown the existence of mutants with loss of the conserved N-glycosylation motif on domain I of protein E that is common to all flaviviruses. 28069378 3 48 theme compromised 614:624 arg1 expression 626:635 expression 626:635 expression 626:635 We found that loss of E N-linked glycosylation leads to compromised expression and secretion of E ectodomain from mammalian cells. 28069378 2 49 gly N-glycosylation 475:489 arg2 motif 491:495 the conserved N-glycosylation motif 461:495 the conserved N-glycosylation motif 461:495 Sequence analysis of different clinical and laboratory isolates has shown the existence of mutants with loss of the conserved N-glycosylation motif on domain I of protein E that is common to all flaviviruses. 28069378 2 50 with mutants 440:446 arg1 loss 453:456 loss 453:456 loss of the conserved N-glycosylation motif 453:495 Sequence analysis of different clinical and laboratory isolates has shown the existence of mutants with loss of the conserved N-glycosylation motif on domain I of protein E that is common to all flaviviruses. 28069378 0 51 theme protein 40:46 arg1 infectivity 78:88 infectivity 78:88 infectivity 78:88 Role of N-glycosylation on Zika virus E protein secretion, viral assembly and infectivity. 28069378 0 51 theme protein 40:46 arg1 secretion 48:56 Zika virus E protein secretion 27:56 Zika virus E protein secretion 27:56 Role of N-glycosylation on Zika virus E protein secretion, viral assembly and infectivity. 28069378 0 51 theme protein 40:46 arg1 assembly 65:72 viral assembly 59:72 viral assembly 59:72 Role of N-glycosylation on Zika virus E protein secretion, viral assembly and infectivity. 28069378 0 52 theme E 38:38 arg1 infectivity 78:88 infectivity 78:88 infectivity 78:88 Role of N-glycosylation on Zika virus E protein secretion, viral assembly and infectivity. 28069378 0 52 theme E 38:38 arg1 secretion 48:56 Zika virus E protein secretion 27:56 Zika virus E protein secretion 27:56 Role of N-glycosylation on Zika virus E protein secretion, viral assembly and infectivity. 28069378 0 52 theme E 38:38 arg1 assembly 65:72 viral assembly 59:72 viral assembly 59:72 Role of N-glycosylation on Zika virus E protein secretion, viral assembly and infectivity. 28069378 6 53 theme impaired 1258:1265 arg1 infectivity 1267:1277 impaired infectivity 1258:1277 impaired infectivity of Vero cells 1258:1291 Production of pseudoviral particles with a West Nile virus replicon packaged with the Zika virus structural proteins C-PrM-E was significantly reduced with the non-glycosylated E. Similarly, glycosylation-negative pseudoviral particles showed impaired infectivity of Vero cells and reduced ability to infect K562 cells upon particles opsonisation with anti-E antibodies. 28069378 6 54 theme particles 1339:1347 arg1 opsonisation 1349:1360 particles opsonisation 1339:1360 particles opsonisation with anti-E antibodies 1339:1383 Production of pseudoviral particles with a West Nile virus replicon packaged with the Zika virus structural proteins C-PrM-E was significantly reduced with the non-glycosylated E. Similarly, glycosylation-negative pseudoviral particles showed impaired infectivity of Vero cells and reduced ability to infect K562 cells upon particles opsonisation with anti-E antibodies. 28069378 3 55 theme ectodomain 656:665 arg1 secretion 641:649 secretion 641:649 secretion 641:649 We found that loss of E N-linked glycosylation leads to compromised expression and secretion of E ectodomain from mammalian cells. 28069378 3 55 theme ectodomain 656:665 arg1 expression 626:635 expression 626:635 expression 626:635 We found that loss of E N-linked glycosylation leads to compromised expression and secretion of E ectodomain from mammalian cells. 28069378 6 56 theme cells 1287:1291 arg1 ability 1305:1311 reduced ability 1297:1311 reduced ability to infect K562 cells upon particles opsonisation with anti-E antibodies 1297:1383 Production of pseudoviral particles with a West Nile virus replicon packaged with the Zika virus structural proteins C-PrM-E was significantly reduced with the non-glycosylated E. Similarly, glycosylation-negative pseudoviral particles showed impaired infectivity of Vero cells and reduced ability to infect K562 cells upon particles opsonisation with anti-E antibodies. 28069378 6 56 theme cells 1287:1291 arg1 infectivity 1267:1277 impaired infectivity 1258:1277 impaired infectivity of Vero cells 1258:1291 Production of pseudoviral particles with a West Nile virus replicon packaged with the Zika virus structural proteins C-PrM-E was significantly reduced with the non-glycosylated E. Similarly, glycosylation-negative pseudoviral particles showed impaired infectivity of Vero cells and reduced ability to infect K562 cells upon particles opsonisation with anti-E antibodies. 28069378 6 57 theme structural 1112:1121 arg1 proteins 1123:1130 the Zika virus structural proteins C-PrM-E 1097:1138 the Zika virus structural proteins C-PrM-E 1097:1138 Production of pseudoviral particles with a West Nile virus replicon packaged with the Zika virus structural proteins C-PrM-E was significantly reduced with the non-glycosylated E. Similarly, glycosylation-negative pseudoviral particles showed impaired infectivity of Vero cells and reduced ability to infect K562 cells upon particles opsonisation with anti-E antibodies. 28069378 4 58 theme viral 798:802 arg1 protein 804:810 the PrM viral protein 790:810 the PrM viral protein 790:810 For both, wild type and glycosylation-negative mutant, secretion was independent of co-expression of the PrM viral protein, but highly dependent on temperature. 28069378 5 59 theme mutant 921:926 arg1 ectodomain 930:939 the glycosylation mutant E ectodomain 903:939 the glycosylation mutant E ectodomain 903:939 Low temperature (28 °C) favoured secretion, although the glycosylation mutant E ectodomain showed impaired secretion and membrane display compared to the wild type. 28069378 6 60 theme pseudoviral 1229:1239 arg1 particles 1241:1249 glycosylation-negative pseudoviral particles 1206:1249 glycosylation-negative pseudoviral particles 1206:1249 Production of pseudoviral particles with a West Nile virus replicon packaged with the Zika virus structural proteins C-PrM-E was significantly reduced with the non-glycosylated E. Similarly, glycosylation-negative pseudoviral particles showed impaired infectivity of Vero cells and reduced ability to infect K562 cells upon particles opsonisation with anti-E antibodies. 28069378 3 61 theme E 580:580 arg1 glycosylation 591:603 E N-linked glycosylation 580:603 E N-linked glycosylation 580:603 We found that loss of E N-linked glycosylation leads to compromised expression and secretion of E ectodomain from mammalian cells. 28069378 6 62 theme virus 1106:1110 arg1 proteins 1123:1130 the Zika virus structural proteins C-PrM-E 1097:1138 the Zika virus structural proteins C-PrM-E 1097:1138 Production of pseudoviral particles with a West Nile virus replicon packaged with the Zika virus structural proteins C-PrM-E was significantly reduced with the non-glycosylated E. Similarly, glycosylation-negative pseudoviral particles showed impaired infectivity of Vero cells and reduced ability to infect K562 cells upon particles opsonisation with anti-E antibodies. 28069378 6 63 theme Zika 1101:1104 arg1 proteins 1123:1130 the Zika virus structural proteins C-PrM-E 1097:1138 the Zika virus structural proteins C-PrM-E 1097:1138 Production of pseudoviral particles with a West Nile virus replicon packaged with the Zika virus structural proteins C-PrM-E was significantly reduced with the non-glycosylated E. Similarly, glycosylation-negative pseudoviral particles showed impaired infectivity of Vero cells and reduced ability to infect K562 cells upon particles opsonisation with anti-E antibodies. 28069378 4 64 theme co-expression 773:785 arg1 independent 758:768 independent 758:768 independent 758:768 For both, wild type and glycosylation-negative mutant, secretion was independent of co-expression of the PrM viral protein, but highly dependent on temperature. 28069378 4 65 theme wild 699:702 arg1 type 704:707 wild type 699:707 wild type 699:707 For both, wild type and glycosylation-negative mutant, secretion was independent of co-expression of the PrM viral protein, but highly dependent on temperature. 28069378 3 66 theme E 654:654 arg1 ectodomain 656:665 E ectodomain 654:665 E ectodomain from mammalian cells 654:686 We found that loss of E N-linked glycosylation leads to compromised expression and secretion of E ectodomain from mammalian cells. 28069378 3 67 theme N-linked 582:589 arg1 glycosylation 591:603 E N-linked glycosylation 580:603 E N-linked glycosylation 580:603 We found that loss of E N-linked glycosylation leads to compromised expression and secretion of E ectodomain from mammalian cells. 28069378 2 68 theme different 370:378 arg1 isolates 404:411 different clinical and laboratory isolates 370:411 different clinical and laboratory isolates 370:411 Sequence analysis of different clinical and laboratory isolates has shown the existence of mutants with loss of the conserved N-glycosylation motif on domain I of protein E that is common to all flaviviruses. 28069378 2 69 theme laboratory 393:402 arg1 isolates 404:411 different clinical and laboratory isolates 370:411 different clinical and laboratory isolates 370:411 Sequence analysis of different clinical and laboratory isolates has shown the existence of mutants with loss of the conserved N-glycosylation motif on domain I of protein E that is common to all flaviviruses. 28069378 3 70 theme glycosylation 591:603 arg1 loss 572:575 loss 572:575 loss of E N-linked glycosylation 572:603 We found that loss of E N-linked glycosylation leads to compromised expression and secretion of E ectodomain from mammalian cells. 28069378 2 71 from existence 427:435 arg1 domain 500:505 domain I 500:507 domain I of protein E that is common to all flaviviruses 500:555 Sequence analysis of different clinical and laboratory isolates has shown the existence of mutants with loss of the conserved N-glycosylation motif on domain I of protein E that is common to all flaviviruses. 28069378 2 71 from existence 427:435 arg1 E 520:520 protein E 512:520 protein E that is common to all flaviviruses 512:555 Sequence analysis of different clinical and laboratory isolates has shown the existence of mutants with loss of the conserved N-glycosylation motif on domain I of protein E that is common to all flaviviruses. 28069378 3 72 from expression 626:635 arg1 cells 682:686 mammalian cells 672:686 mammalian cells 672:686 We found that loss of E N-linked glycosylation leads to compromised expression and secretion of E ectodomain from mammalian cells. 32624756 7 0 theme activity 1123:1130 arg1 inhibition 1081:1090 dose-dependent inhibition 1066:1090 dose-dependent inhibition of APRIL-induced proliferative activity 1066:1130 The purified functional rhBCMA-Fc possessed high-binding affinity to APRIL and dose-dependent inhibition of APRIL-induced proliferative activity in vitro through three-step purification. 32624756 7 0 theme activity 1123:1130 arg1 affinity 1044:1051 high-binding affinity 1031:1051 high-binding affinity to APRIL 1031:1060 The purified functional rhBCMA-Fc possessed high-binding affinity to APRIL and dose-dependent inhibition of APRIL-induced proliferative activity in vitro through three-step purification. 32624756 8 1 from production 1270:1279 arg1 lines 1312:1316 mammalian cell lines 1297:1316 mammalian cell lines 1297:1316 Thus, this yeast-derived expression method could be a low-cost and effective alternative to the production of rhBCMA-Fc in mammalian cell lines. 32624756 1 2 dep -mediated 290:298 arg1 ligand 276:281 proliferation-inducing ligand 253:281 proliferation-inducing ligand 253:281 B-cell maturation antigen (BCMA) fused at the C-terminus to the Fc portion of human IgG1 (BCMA-Fc) blocks B-cell activating factor (BAFF) and proliferation-inducing ligand (APRIL)-mediated B-cell activation, leading to immune disorders. 32624756 1 2 dep -mediated 290:298 arg1 BAFF 243:246 BAFF 243:246 BAFF 243:246 B-cell maturation antigen (BCMA) fused at the C-terminus to the Fc portion of human IgG1 (BCMA-Fc) blocks B-cell activating factor (BAFF) and proliferation-inducing ligand (APRIL)-mediated B-cell activation, leading to immune disorders. 32624756 1 2 dep -mediated 290:298 arg1 factor 235:240 B-cell activating factor 217:240 B-cell activating factor (BAFF) 217:247 B-cell maturation antigen (BCMA) fused at the C-terminus to the Fc portion of human IgG1 (BCMA-Fc) blocks B-cell activating factor (BAFF) and proliferation-inducing ligand (APRIL)-mediated B-cell activation, leading to immune disorders. 32624756 0 3 theme Pichia 94:99 arg1 pastoris 101:108 Pichia pastoris 94:108 Pichia pastoris 94:108 Characterization and high-yield production of non-N-glycosylated recombinant human BCMA-Fc in Pichia pastoris. 32624756 5 4 theme secretory 757:765 arg1 yield 767:771 The secretory yield 753:771 The secretory yield 753:771 The secretory yield was improved by codon optimization of the target gene sequence. 32624756 3 5 from BCMA-Fc 512:518 arg1 pastoris 542:549 Pichia pastoris 535:549 Pichia pastoris 535:549 To reduce cost and enhance production, we attempted to express recombinant human BCMA-Fc (rhBCMA-Fc) in Pichia pastoris under the control of the AOX1 methanol-inducible promoter. 32624756 0 6 from Characterization 0:15 arg1 pastoris 101:108 Pichia pastoris 94:108 Pichia pastoris 94:108 Characterization and high-yield production of non-N-glycosylated recombinant human BCMA-Fc in Pichia pastoris. 32624756 7 7 theme APRIL-induced 1095:1107 arg1 activity 1123:1130 APRIL-induced proliferative activity 1095:1130 APRIL-induced proliferative activity 1095:1130 The purified functional rhBCMA-Fc possessed high-binding affinity to APRIL and dose-dependent inhibition of APRIL-induced proliferative activity in vitro through three-step purification. 32624756 6 8 theme fed-batch 843:851 arg1 fermentation 853:864 fed-batch fermentation 843:864 fed-batch fermentation under optimized conditions 843:891 After fed-batch fermentation under optimized conditions, the highest yield (207 mg/L) of rhBCMA-Fc was obtained with high productivity (3.45 mg/L/h). 32624756 1 9 theme immune 330:335 arg1 disorders 337:345 immune disorders 330:345 immune disorders 330:345 B-cell maturation antigen (BCMA) fused at the C-terminus to the Fc portion of human IgG1 (BCMA-Fc) blocks B-cell activating factor (BAFF) and proliferation-inducing ligand (APRIL)-mediated B-cell activation, leading to immune disorders. 32624756 7 10 theme proliferative 1109:1121 arg1 activity 1123:1130 APRIL-induced proliferative activity 1095:1130 APRIL-induced proliferative activity 1095:1130 The purified functional rhBCMA-Fc possessed high-binding affinity to APRIL and dose-dependent inhibition of APRIL-induced proliferative activity in vitro through three-step purification. 32624756 7 11 theme three-step 1149:1158 arg1 purification 1160:1171 three-step purification 1149:1171 three-step purification 1149:1171 The purified functional rhBCMA-Fc possessed high-binding affinity to APRIL and dose-dependent inhibition of APRIL-induced proliferative activity in vitro through three-step purification. 32624756 4 12 theme glycosylation 732:744 arg1 sites 746:750 two predicted N-linked glycosylation sites 709:750 two predicted N-linked glycosylation sites 709:750 To produce the target protein with uniform molecular weight and reduced immunogenicity, we mutated two predicted N-linked glycosylation sites. 32624756 6 13 theme high 954:957 arg1 productivity 959:970 high productivity 954:970 high productivity (3.45 mg/L/h) 954:984 After fed-batch fermentation under optimized conditions, the highest yield (207 mg/L) of rhBCMA-Fc was obtained with high productivity (3.45 mg/L/h). 32624756 6 13 theme high 954:957 arg1 mg/L/h 978:983 3.45 mg/L/h 973:983 3.45 mg/L/h 973:983 After fed-batch fermentation under optimized conditions, the highest yield (207 mg/L) of rhBCMA-Fc was obtained with high productivity (3.45 mg/L/h). 32624756 5 14 theme target 815:820 arg1 sequence 827:834 the target gene sequence 811:834 the target gene sequence 811:834 The secretory yield was improved by codon optimization of the target gene sequence. 32624756 3 15 theme recombinant 494:504 arg1 BCMA-Fc 512:518 recombinant human BCMA-Fc 494:518 recombinant human BCMA-Fc (rhBCMA-Fc) in Pichia pastoris 494:549 To reduce cost and enhance production, we attempted to express recombinant human BCMA-Fc (rhBCMA-Fc) in Pichia pastoris under the control of the AOX1 methanol-inducible promoter. 32624756 3 15 theme recombinant 494:504 arg1 rhBCMA-Fc 521:529 rhBCMA-Fc 521:529 rhBCMA-Fc 521:529 To reduce cost and enhance production, we attempted to express recombinant human BCMA-Fc (rhBCMA-Fc) in Pichia pastoris under the control of the AOX1 methanol-inducible promoter. 32624756 4 16 theme target 625:630 arg1 protein 632:638 the target protein 621:638 the target protein with uniform molecular weight and reduced immunogenicity 621:695 To produce the target protein with uniform molecular weight and reduced immunogenicity, we mutated two predicted N-linked glycosylation sites. 32624756 8 17 theme low-cost 1228:1235 arg1 method 1210:1215 this yeast-derived expression method 1180:1215 this yeast-derived expression method 1180:1215 Thus, this yeast-derived expression method could be a low-cost and effective alternative to the production of rhBCMA-Fc in mammalian cell lines. 32624756 8 17 theme low-cost 1228:1235 arg1 alternative 1251:1261 a low-cost and effective alternative 1226:1261 a low-cost and effective alternative to the production of rhBCMA-Fc in mammalian cell lines 1226:1316 Thus, this yeast-derived expression method could be a low-cost and effective alternative to the production of rhBCMA-Fc in mammalian cell lines. 32624756 6 18 theme optimized 872:880 arg1 conditions 882:891 optimized conditions 872:891 optimized conditions 872:891 After fed-batch fermentation under optimized conditions, the highest yield (207 mg/L) of rhBCMA-Fc was obtained with high productivity (3.45 mg/L/h). 32624756 5 19 theme codon 789:793 arg1 optimization 795:806 codon optimization 789:806 codon optimization of the target gene sequence 789:834 The secretory yield was improved by codon optimization of the target gene sequence. 32624756 3 20 theme human 506:510 arg1 BCMA-Fc 512:518 recombinant human BCMA-Fc 494:518 recombinant human BCMA-Fc (rhBCMA-Fc) in Pichia pastoris 494:549 To reduce cost and enhance production, we attempted to express recombinant human BCMA-Fc (rhBCMA-Fc) in Pichia pastoris under the control of the AOX1 methanol-inducible promoter. 32624756 3 20 theme human 506:510 arg1 rhBCMA-Fc 521:529 rhBCMA-Fc 521:529 rhBCMA-Fc 521:529 To reduce cost and enhance production, we attempted to express recombinant human BCMA-Fc (rhBCMA-Fc) in Pichia pastoris under the control of the AOX1 methanol-inducible promoter. 32624756 7 21 contain possessed 1021:1029 arg1 rhBCMA-Fc 1011:1019 The purified functional rhBCMA-Fc 987:1019 The purified functional rhBCMA-Fc 987:1019 The purified functional rhBCMA-Fc possessed high-binding affinity to APRIL and dose-dependent inhibition of APRIL-induced proliferative activity in vitro through three-step purification. 32624756 7 21 contain possessed 1021:1029 arg2 affinity 1044:1051 high-binding affinity 1031:1051 high-binding affinity to APRIL 1031:1060 The purified functional rhBCMA-Fc possessed high-binding affinity to APRIL and dose-dependent inhibition of APRIL-induced proliferative activity in vitro through three-step purification. 32624756 7 21 contain possessed 1021:1029 arg2 inhibition 1081:1090 dose-dependent inhibition 1066:1090 dose-dependent inhibition of APRIL-induced proliferative activity 1066:1130 The purified functional rhBCMA-Fc possessed high-binding affinity to APRIL and dose-dependent inhibition of APRIL-induced proliferative activity in vitro through three-step purification. 32624756 1 22 theme Fc 175:176 arg1 portion 178:184 the Fc portion 171:184 the Fc portion of human IgG1 (BCMA-Fc) 171:208 B-cell maturation antigen (BCMA) fused at the C-terminus to the Fc portion of human IgG1 (BCMA-Fc) blocks B-cell activating factor (BAFF) and proliferation-inducing ligand (APRIL)-mediated B-cell activation, leading to immune disorders. 32624756 8 23 theme expression 1199:1208 arg1 method 1210:1215 this yeast-derived expression method 1180:1215 this yeast-derived expression method 1180:1215 Thus, this yeast-derived expression method could be a low-cost and effective alternative to the production of rhBCMA-Fc in mammalian cell lines. 32624756 8 23 theme expression 1199:1208 arg1 alternative 1251:1261 a low-cost and effective alternative 1226:1261 a low-cost and effective alternative to the production of rhBCMA-Fc in mammalian cell lines 1226:1316 Thus, this yeast-derived expression method could be a low-cost and effective alternative to the production of rhBCMA-Fc in mammalian cell lines. 32624756 8 24 theme yeast-derived 1185:1197 arg1 method 1210:1215 this yeast-derived expression method 1180:1215 this yeast-derived expression method 1180:1215 Thus, this yeast-derived expression method could be a low-cost and effective alternative to the production of rhBCMA-Fc in mammalian cell lines. 32624756 8 24 theme yeast-derived 1185:1197 arg1 alternative 1251:1261 a low-cost and effective alternative 1226:1261 a low-cost and effective alternative to the production of rhBCMA-Fc in mammalian cell lines 1226:1316 Thus, this yeast-derived expression method could be a low-cost and effective alternative to the production of rhBCMA-Fc in mammalian cell lines. 32624756 2 25 theme cell 419:422 arg1 lines 424:428 several engineering cell lines 399:428 several engineering cell lines 399:428 The fusion protein has been cloned and produced by several engineering cell lines. 32624756 7 26 theme dose-dependent 1066:1079 arg1 inhibition 1081:1090 dose-dependent inhibition 1066:1090 dose-dependent inhibition of APRIL-induced proliferative activity 1066:1130 The purified functional rhBCMA-Fc possessed high-binding affinity to APRIL and dose-dependent inhibition of APRIL-induced proliferative activity in vitro through three-step purification. 32624756 1 27 theme B-cell 111:116 arg1 BCMA 138:141 BCMA 138:141 BCMA 138:141 B-cell maturation antigen (BCMA) fused at the C-terminus to the Fc portion of human IgG1 (BCMA-Fc) blocks B-cell activating factor (BAFF) and proliferation-inducing ligand (APRIL)-mediated B-cell activation, leading to immune disorders. 32624756 1 27 theme B-cell 111:116 arg1 antigen 129:135 B-cell maturation antigen 111:135 B-cell maturation antigen (BCMA) fused at the C-terminus to the Fc portion of human IgG1 (BCMA-Fc) 111:208 B-cell maturation antigen (BCMA) fused at the C-terminus to the Fc portion of human IgG1 (BCMA-Fc) blocks B-cell activating factor (BAFF) and proliferation-inducing ligand (APRIL)-mediated B-cell activation, leading to immune disorders. 32624756 2 28 theme fusion 352:357 arg1 protein 359:365 The fusion protein 348:365 The fusion protein 348:365 The fusion protein has been cloned and produced by several engineering cell lines. 32624756 2 29 theme engineering 407:417 arg1 lines 424:428 several engineering cell lines 399:428 several engineering cell lines 399:428 The fusion protein has been cloned and produced by several engineering cell lines. 32624756 1 30 theme proliferation-inducing 253:274 arg1 ligand 276:281 proliferation-inducing ligand 253:281 proliferation-inducing ligand 253:281 B-cell maturation antigen (BCMA) fused at the C-terminus to the Fc portion of human IgG1 (BCMA-Fc) blocks B-cell activating factor (BAFF) and proliferation-inducing ligand (APRIL)-mediated B-cell activation, leading to immune disorders. 32624756 8 31 link yeast-derived 1185:1197 arg1 method 1210:1215 this yeast-derived expression method 1180:1215 this yeast-derived expression method 1180:1215 Thus, this yeast-derived expression method could be a low-cost and effective alternative to the production of rhBCMA-Fc in mammalian cell lines. 32624756 8 31 link yeast-derived 1185:1197 arg1 alternative 1251:1261 a low-cost and effective alternative 1226:1261 a low-cost and effective alternative to the production of rhBCMA-Fc in mammalian cell lines 1226:1316 Thus, this yeast-derived expression method could be a low-cost and effective alternative to the production of rhBCMA-Fc in mammalian cell lines. 32624756 1 32 theme maturation 118:127 arg1 BCMA 138:141 BCMA 138:141 BCMA 138:141 B-cell maturation antigen (BCMA) fused at the C-terminus to the Fc portion of human IgG1 (BCMA-Fc) blocks B-cell activating factor (BAFF) and proliferation-inducing ligand (APRIL)-mediated B-cell activation, leading to immune disorders. 32624756 1 32 theme maturation 118:127 arg1 antigen 129:135 B-cell maturation antigen 111:135 B-cell maturation antigen (BCMA) fused at the C-terminus to the Fc portion of human IgG1 (BCMA-Fc) 111:208 B-cell maturation antigen (BCMA) fused at the C-terminus to the Fc portion of human IgG1 (BCMA-Fc) blocks B-cell activating factor (BAFF) and proliferation-inducing ligand (APRIL)-mediated B-cell activation, leading to immune disorders. 32624756 1 33 theme human 189:193 arg1 IgG1 195:198 human IgG1 189:198 human IgG1 (BCMA-Fc) 189:208 B-cell maturation antigen (BCMA) fused at the C-terminus to the Fc portion of human IgG1 (BCMA-Fc) blocks B-cell activating factor (BAFF) and proliferation-inducing ligand (APRIL)-mediated B-cell activation, leading to immune disorders. 32624756 1 33 theme human 189:193 arg1 BCMA-Fc 201:207 BCMA-Fc 201:207 BCMA-Fc 201:207 B-cell maturation antigen (BCMA) fused at the C-terminus to the Fc portion of human IgG1 (BCMA-Fc) blocks B-cell activating factor (BAFF) and proliferation-inducing ligand (APRIL)-mediated B-cell activation, leading to immune disorders. 32624756 0 34 theme high-yield 21:30 arg1 production 32:41 high-yield production 21:41 high-yield production 21:41 Characterization and high-yield production of non-N-glycosylated recombinant human BCMA-Fc in Pichia pastoris. 32624756 0 35 from pastoris 101:108 arg1 Characterization 0:15 Characterization 0:15 Characterization 0:15 Characterization and high-yield production of non-N-glycosylated recombinant human BCMA-Fc in Pichia pastoris. 32624756 0 35 from pastoris 101:108 arg1 production 32:41 high-yield production 21:41 high-yield production 21:41 Characterization and high-yield production of non-N-glycosylated recombinant human BCMA-Fc in Pichia pastoris. 32624756 4 36 theme predicted 713:721 arg1 sites 746:750 two predicted N-linked glycosylation sites 709:750 two predicted N-linked glycosylation sites 709:750 To produce the target protein with uniform molecular weight and reduced immunogenicity, we mutated two predicted N-linked glycosylation sites. 32624756 1 37 theme IgG1 195:198 arg1 portion 178:184 the Fc portion 171:184 the Fc portion of human IgG1 (BCMA-Fc) 171:208 B-cell maturation antigen (BCMA) fused at the C-terminus to the Fc portion of human IgG1 (BCMA-Fc) blocks B-cell activating factor (BAFF) and proliferation-inducing ligand (APRIL)-mediated B-cell activation, leading to immune disorders. 32624756 0 38 theme non-N-glycosylated 46:63 arg1 BCMA-Fc 83:89 non-N-glycosylated recombinant human BCMA-Fc 46:89 non-N-glycosylated recombinant human BCMA-Fc in Pichia pastoris 46:108 Characterization and high-yield production of non-N-glycosylated recombinant human BCMA-Fc in Pichia pastoris. 32624756 6 39 theme rhBCMA-Fc 926:934 arg1 yield 906:910 the highest yield 894:910 the highest yield (207 mg/L) of rhBCMA-Fc 894:934 After fed-batch fermentation under optimized conditions, the highest yield (207 mg/L) of rhBCMA-Fc was obtained with high productivity (3.45 mg/L/h). 32624756 6 39 theme rhBCMA-Fc 926:934 arg1 mg/L 917:920 207 mg/L 913:920 207 mg/L 913:920 After fed-batch fermentation under optimized conditions, the highest yield (207 mg/L) of rhBCMA-Fc was obtained with high productivity (3.45 mg/L/h). 32624756 7 40 theme high-binding 1031:1042 arg1 affinity 1044:1051 high-binding affinity 1031:1051 high-binding affinity to APRIL 1031:1060 The purified functional rhBCMA-Fc possessed high-binding affinity to APRIL and dose-dependent inhibition of APRIL-induced proliferative activity in vitro through three-step purification. 32624756 4 41 with protein 632:638 arg1 weight 663:668 uniform molecular weight 645:668 uniform molecular weight 645:668 To produce the target protein with uniform molecular weight and reduced immunogenicity, we mutated two predicted N-linked glycosylation sites. 32624756 4 41 with protein 632:638 arg1 immunogenicity 682:695 reduced immunogenicity 674:695 reduced immunogenicity 674:695 To produce the target protein with uniform molecular weight and reduced immunogenicity, we mutated two predicted N-linked glycosylation sites. 32624756 5 42 theme gene 822:825 arg1 sequence 827:834 the target gene sequence 811:834 the target gene sequence 811:834 The secretory yield was improved by codon optimization of the target gene sequence. 32624756 4 43 theme molecular 653:661 arg1 weight 663:668 uniform molecular weight 645:668 uniform molecular weight 645:668 To produce the target protein with uniform molecular weight and reduced immunogenicity, we mutated two predicted N-linked glycosylation sites. 32624756 3 44 theme methanol-inducible 581:598 arg1 promoter 600:607 the AOX1 methanol-inducible promoter 572:607 the AOX1 methanol-inducible promoter 572:607 To reduce cost and enhance production, we attempted to express recombinant human BCMA-Fc (rhBCMA-Fc) in Pichia pastoris under the control of the AOX1 methanol-inducible promoter. 32624756 3 45 theme promoter 600:607 arg1 control 561:567 the control 557:567 the control of the AOX1 methanol-inducible promoter 557:607 To reduce cost and enhance production, we attempted to express recombinant human BCMA-Fc (rhBCMA-Fc) in Pichia pastoris under the control of the AOX1 methanol-inducible promoter. 32624756 5 46 theme sequence 827:834 arg1 optimization 795:806 codon optimization 789:806 codon optimization of the target gene sequence 789:834 The secretory yield was improved by codon optimization of the target gene sequence. 32624756 0 47 theme human 77:81 arg1 BCMA-Fc 83:89 non-N-glycosylated recombinant human BCMA-Fc 46:89 non-N-glycosylated recombinant human BCMA-Fc in Pichia pastoris 46:108 Characterization and high-yield production of non-N-glycosylated recombinant human BCMA-Fc in Pichia pastoris. 32624756 0 48 from BCMA-Fc 83:89 arg1 pastoris 101:108 Pichia pastoris 94:108 Pichia pastoris 94:108 Characterization and high-yield production of non-N-glycosylated recombinant human BCMA-Fc in Pichia pastoris. 32624756 8 49 theme cell 1307:1310 arg1 lines 1312:1316 mammalian cell lines 1297:1316 mammalian cell lines 1297:1316 Thus, this yeast-derived expression method could be a low-cost and effective alternative to the production of rhBCMA-Fc in mammalian cell lines. 32624756 0 50 theme recombinant 65:75 arg1 BCMA-Fc 83:89 non-N-glycosylated recombinant human BCMA-Fc 46:89 non-N-glycosylated recombinant human BCMA-Fc in Pichia pastoris 46:108 Characterization and high-yield production of non-N-glycosylated recombinant human BCMA-Fc in Pichia pastoris. 32624756 1 51 theme -mediated 290:298 arg1 activation 307:316 B-cell activating factor (BAFF) and proliferation-inducing ligand (APRIL)-mediated B-cell activation 217:316 B-cell activating factor (BAFF) and proliferation-inducing ligand (APRIL)-mediated B-cell activation 217:316 B-cell maturation antigen (BCMA) fused at the C-terminus to the Fc portion of human IgG1 (BCMA-Fc) blocks B-cell activating factor (BAFF) and proliferation-inducing ligand (APRIL)-mediated B-cell activation, leading to immune disorders. 32624756 6 52 theme highest 898:904 arg1 yield 906:910 the highest yield 894:910 the highest yield (207 mg/L) of rhBCMA-Fc 894:934 After fed-batch fermentation under optimized conditions, the highest yield (207 mg/L) of rhBCMA-Fc was obtained with high productivity (3.45 mg/L/h). 32624756 6 52 theme highest 898:904 arg1 mg/L 917:920 207 mg/L 913:920 207 mg/L 913:920 After fed-batch fermentation under optimized conditions, the highest yield (207 mg/L) of rhBCMA-Fc was obtained with high productivity (3.45 mg/L/h). 32624756 4 53 theme reduced 674:680 arg1 immunogenicity 682:695 reduced immunogenicity 674:695 reduced immunogenicity 674:695 To produce the target protein with uniform molecular weight and reduced immunogenicity, we mutated two predicted N-linked glycosylation sites. 32624756 1 54 theme B-cell 300:305 arg1 activation 307:316 B-cell activating factor (BAFF) and proliferation-inducing ligand (APRIL)-mediated B-cell activation 217:316 B-cell activating factor (BAFF) and proliferation-inducing ligand (APRIL)-mediated B-cell activation 217:316 B-cell maturation antigen (BCMA) fused at the C-terminus to the Fc portion of human IgG1 (BCMA-Fc) blocks B-cell activating factor (BAFF) and proliferation-inducing ligand (APRIL)-mediated B-cell activation, leading to immune disorders. 32624756 7 55 theme purified 991:998 arg1 rhBCMA-Fc 1011:1019 The purified functional rhBCMA-Fc 987:1019 The purified functional rhBCMA-Fc 987:1019 The purified functional rhBCMA-Fc possessed high-binding affinity to APRIL and dose-dependent inhibition of APRIL-induced proliferative activity in vitro through three-step purification. 32624756 3 56 theme AOX1 576:579 arg1 promoter 600:607 the AOX1 methanol-inducible promoter 572:607 the AOX1 methanol-inducible promoter 572:607 To reduce cost and enhance production, we attempted to express recombinant human BCMA-Fc (rhBCMA-Fc) in Pichia pastoris under the control of the AOX1 methanol-inducible promoter. 32624756 4 57 theme N-linked 723:730 arg1 sites 746:750 two predicted N-linked glycosylation sites 709:750 two predicted N-linked glycosylation sites 709:750 To produce the target protein with uniform molecular weight and reduced immunogenicity, we mutated two predicted N-linked glycosylation sites. 32624756 7 58 theme functional 1000:1009 arg1 rhBCMA-Fc 1011:1019 The purified functional rhBCMA-Fc 987:1019 The purified functional rhBCMA-Fc 987:1019 The purified functional rhBCMA-Fc possessed high-binding affinity to APRIL and dose-dependent inhibition of APRIL-induced proliferative activity in vitro through three-step purification. 32624756 0 59 gly non-N-glycosylated 46:63 arg1 BCMA-Fc 83:89 non-N-glycosylated recombinant human BCMA-Fc 46:89 non-N-glycosylated recombinant human BCMA-Fc in Pichia pastoris 46:108 Characterization and high-yield production of non-N-glycosylated recombinant human BCMA-Fc in Pichia pastoris. 32624756 4 60 theme uniform 645:651 arg1 weight 663:668 uniform molecular weight 645:668 uniform molecular weight 645:668 To produce the target protein with uniform molecular weight and reduced immunogenicity, we mutated two predicted N-linked glycosylation sites. 32624756 4 61 gly glycosylation 732:744 arg2 sites 746:750 two predicted N-linked glycosylation sites 709:750 two predicted N-linked glycosylation sites 709:750 To produce the target protein with uniform molecular weight and reduced immunogenicity, we mutated two predicted N-linked glycosylation sites. 32624756 4 61 gly glycosylation 732:744 arg2 two 709:711 two 709:711 two 709:711 To produce the target protein with uniform molecular weight and reduced immunogenicity, we mutated two predicted N-linked glycosylation sites. 32624756 8 62 theme rhBCMA-Fc 1284:1292 arg1 production 1270:1279 the production 1266:1279 the production of rhBCMA-Fc in mammalian cell lines 1266:1316 Thus, this yeast-derived expression method could be a low-cost and effective alternative to the production of rhBCMA-Fc in mammalian cell lines. 32624756 4 63 link N-linked 723:730 arg1 sites 746:750 two predicted N-linked glycosylation sites 709:750 two predicted N-linked glycosylation sites 709:750 To produce the target protein with uniform molecular weight and reduced immunogenicity, we mutated two predicted N-linked glycosylation sites. 32624756 8 64 theme effective 1241:1249 arg1 method 1210:1215 this yeast-derived expression method 1180:1215 this yeast-derived expression method 1180:1215 Thus, this yeast-derived expression method could be a low-cost and effective alternative to the production of rhBCMA-Fc in mammalian cell lines. 32624756 8 64 theme effective 1241:1249 arg1 alternative 1251:1261 a low-cost and effective alternative 1226:1261 a low-cost and effective alternative to the production of rhBCMA-Fc in mammalian cell lines 1226:1316 Thus, this yeast-derived expression method could be a low-cost and effective alternative to the production of rhBCMA-Fc in mammalian cell lines. 32624756 1 65 theme B-cell 217:222 arg1 BAFF 243:246 BAFF 243:246 BAFF 243:246 B-cell maturation antigen (BCMA) fused at the C-terminus to the Fc portion of human IgG1 (BCMA-Fc) blocks B-cell activating factor (BAFF) and proliferation-inducing ligand (APRIL)-mediated B-cell activation, leading to immune disorders. 32624756 1 65 theme B-cell 217:222 arg1 factor 235:240 B-cell activating factor 217:240 B-cell activating factor (BAFF) 217:247 B-cell maturation antigen (BCMA) fused at the C-terminus to the Fc portion of human IgG1 (BCMA-Fc) blocks B-cell activating factor (BAFF) and proliferation-inducing ligand (APRIL)-mediated B-cell activation, leading to immune disorders. 32624756 0 66 theme BCMA-Fc 83:89 arg1 Characterization 0:15 Characterization 0:15 Characterization 0:15 Characterization and high-yield production of non-N-glycosylated recombinant human BCMA-Fc in Pichia pastoris. 32624756 0 66 theme BCMA-Fc 83:89 arg1 production 32:41 high-yield production 21:41 high-yield production 21:41 Characterization and high-yield production of non-N-glycosylated recombinant human BCMA-Fc in Pichia pastoris. 32624756 0 67 from production 32:41 arg1 pastoris 101:108 Pichia pastoris 94:108 Pichia pastoris 94:108 Characterization and high-yield production of non-N-glycosylated recombinant human BCMA-Fc in Pichia pastoris. 32624756 2 68 theme several 399:405 arg1 lines 424:428 several engineering cell lines 399:428 several engineering cell lines 399:428 The fusion protein has been cloned and produced by several engineering cell lines. 32624756 3 69 theme Pichia 535:540 arg1 pastoris 542:549 Pichia pastoris 535:549 Pichia pastoris 535:549 To reduce cost and enhance production, we attempted to express recombinant human BCMA-Fc (rhBCMA-Fc) in Pichia pastoris under the control of the AOX1 methanol-inducible promoter. 32624756 8 70 theme mammalian 1297:1305 arg1 lines 1312:1316 mammalian cell lines 1297:1316 mammalian cell lines 1297:1316 Thus, this yeast-derived expression method could be a low-cost and effective alternative to the production of rhBCMA-Fc in mammalian cell lines. 32624756 1 71 theme activating 224:233 arg1 BAFF 243:246 BAFF 243:246 BAFF 243:246 B-cell maturation antigen (BCMA) fused at the C-terminus to the Fc portion of human IgG1 (BCMA-Fc) blocks B-cell activating factor (BAFF) and proliferation-inducing ligand (APRIL)-mediated B-cell activation, leading to immune disorders. 32624756 1 71 theme activating 224:233 arg1 factor 235:240 B-cell activating factor 217:240 B-cell activating factor (BAFF) 217:247 B-cell maturation antigen (BCMA) fused at the C-terminus to the Fc portion of human IgG1 (BCMA-Fc) blocks B-cell activating factor (BAFF) and proliferation-inducing ligand (APRIL)-mediated B-cell activation, leading to immune disorders. 26888493 5 0 theme high 909:912 arg1 fmol 931:934 0.1 fmol 927:934 0.1 fmol 927:934 By virtue of the features contributed by different ingredients, the prepared composites demonstrated superior performance for glycopeptide enrichment with high sensitivity (0.1 fmol), efficiency, selectivity (1:100), and repeatability (at least ten times). 26888493 5 0 theme high 909:912 arg1 sensitivity 914:924 high sensitivity 909:924 high sensitivity (0.1 fmol) 909:935 By virtue of the features contributed by different ingredients, the prepared composites demonstrated superior performance for glycopeptide enrichment with high sensitivity (0.1 fmol), efficiency, selectivity (1:100), and repeatability (at least ten times). 26888493 1 1 theme biological 186:195 arg1 samples 197:203 complex biological samples 178:203 complex biological samples 178:203 Highly selective and efficient enrichment of glycopeptides from complex biological samples is necessary. 26888493 6 2 gly glycoproteins 1183:1195 arg1 glycoproteins 1183:1195 31 different N-linked glycoproteins 1161:1195 31 different N-linked glycoproteins 1161:1195 In addition, the composites were successfully applied to the enrichment of glycopeptides from human serum and 40 unique N-glycosylation peptides from 31 different N-linked glycoproteins were identified. 26888493 4 3 theme good 677:680 arg1 property 715:722 good biocompatibility easy separation property 677:722 good biocompatibility easy separation property 677:722 The composites possessed a number of desirable characteristics, including good biocompatibility easy separation property and excellent hydrophilicity. 26888493 0 4 theme magG/PDA/Au/l-Cys 84:100 arg1 composites 102:111 easily synthesized magG/PDA/Au/l-Cys composites 65:111 easily synthesized magG/PDA/Au/l-Cys composites 65:111 Highly efficient and selective enrichment of glycopeptides using easily synthesized magG/PDA/Au/l-Cys composites. 26888493 6 5 from serum 1111:1115 arg1 glycopeptides 1086:1098 glycopeptides 1086:1098 glycopeptides from human serum 1086:1115 In addition, the composites were successfully applied to the enrichment of glycopeptides from human serum and 40 unique N-glycosylation peptides from 31 different N-linked glycoproteins were identified. 26888493 6 5 from serum 1111:1115 arg1 enrichment 1072:1081 the enrichment 1068:1081 the enrichment of glycopeptides from human serum 1068:1115 In addition, the composites were successfully applied to the enrichment of glycopeptides from human serum and 40 unique N-glycosylation peptides from 31 different N-linked glycoproteins were identified. 26888493 7 6 theme great 1254:1258 arg1 potential 1260:1268 great potential 1254:1268 great potential 1254:1268 The superior hydrophilic material is of great potential for the analysis of glycoproteins. 26888493 5 7 theme superior 855:862 arg1 performance 864:874 superior performance 855:874 superior performance for glycopeptide enrichment with high sensitivity (0.1 fmol), efficiency, selectivity (1:100), and repeatability (at least ten times) 855:1008 By virtue of the features contributed by different ingredients, the prepared composites demonstrated superior performance for glycopeptide enrichment with high sensitivity (0.1 fmol), efficiency, selectivity (1:100), and repeatability (at least ten times). 26888493 5 8 theme features 771:778 arg1 virtue 757:762 virtue 757:762 virtue of the features contributed by different ingredients 757:815 By virtue of the features contributed by different ingredients, the prepared composites demonstrated superior performance for glycopeptide enrichment with high sensitivity (0.1 fmol), efficiency, selectivity (1:100), and repeatability (at least ten times). 26888493 1 9 from samples 197:203 arg1 enrichment 145:154 Highly selective and efficient enrichment 114:154 Highly selective and efficient enrichment of glycopeptides from complex biological samples 114:203 Highly selective and efficient enrichment of glycopeptides from complex biological samples is necessary. 26888493 4 10 theme easy 699:702 arg1 property 715:722 good biocompatibility easy separation property 677:722 good biocompatibility easy separation property 677:722 The composites possessed a number of desirable characteristics, including good biocompatibility easy separation property and excellent hydrophilicity. 26888493 3 11 theme X-ray 584:588 arg1 diffraction 590:600 X-ray diffraction 584:600 X-ray diffraction 584:600 The size, morphology, and composition of magG/PDA/Au/l-Cys composites were investigated by transmission electron microscopy, scanning electron microscopy, FT-infrared spectroscopy, and X-ray diffraction. 26888493 4 12 theme biocompatibility 682:697 arg1 property 715:722 good biocompatibility easy separation property 677:722 good biocompatibility easy separation property 677:722 The composites possessed a number of desirable characteristics, including good biocompatibility easy separation property and excellent hydrophilicity. 26888493 6 13 from glycoproteins 1183:1195 arg1 peptides 1147:1154 40 unique N-glycosylation peptides 1121:1154 40 unique N-glycosylation peptides from 31 different N-linked glycoproteins 1121:1195 In addition, the composites were successfully applied to the enrichment of glycopeptides from human serum and 40 unique N-glycosylation peptides from 31 different N-linked glycoproteins were identified. 26888493 6 14 theme N-linked 1174:1181 arg1 glycoproteins 1183:1195 31 different N-linked glycoproteins 1161:1195 31 different N-linked glycoproteins 1161:1195 In addition, the composites were successfully applied to the enrichment of glycopeptides from human serum and 40 unique N-glycosylation peptides from 31 different N-linked glycoproteins were identified. 26888493 5 15 theme glycopeptide 880:891 arg1 enrichment 893:902 glycopeptide enrichment 880:902 glycopeptide enrichment with high sensitivity (0.1 fmol), efficiency, selectivity (1:100), and repeatability (at least ten times) 880:1008 By virtue of the features contributed by different ingredients, the prepared composites demonstrated superior performance for glycopeptide enrichment with high sensitivity (0.1 fmol), efficiency, selectivity (1:100), and repeatability (at least ten times). 26888493 6 16 theme human 1105:1109 arg1 serum 1111:1115 human serum 1105:1115 human serum 1105:1115 In addition, the composites were successfully applied to the enrichment of glycopeptides from human serum and 40 unique N-glycosylation peptides from 31 different N-linked glycoproteins were identified. 26888493 4 17 contain possessed 618:626 arg2 hydrophilicity 738:751 excellent hydrophilicity 728:751 excellent hydrophilicity 728:751 The composites possessed a number of desirable characteristics, including good biocompatibility easy separation property and excellent hydrophilicity. 26888493 4 17 contain possessed 618:626 arg1 composites 607:616 The composites 603:616 The composites 603:616 The composites possessed a number of desirable characteristics, including good biocompatibility easy separation property and excellent hydrophilicity. 26888493 4 17 contain possessed 618:626 arg2 number 630:635 a number 628:635 a number of desirable characteristics, including good biocompatibility easy separation property and excellent hydrophilicity 628:751 The composites possessed a number of desirable characteristics, including good biocompatibility easy separation property and excellent hydrophilicity. 26888493 4 17 contain possessed 618:626 arg2 property 715:722 good biocompatibility easy separation property 677:722 good biocompatibility easy separation property 677:722 The composites possessed a number of desirable characteristics, including good biocompatibility easy separation property and excellent hydrophilicity. 26888493 0 18 theme efficient 7:15 arg1 enrichment 31:40 Highly efficient and selective enrichment 0:40 Highly efficient and selective enrichment of glycopeptides 0:57 Highly efficient and selective enrichment of glycopeptides using easily synthesized magG/PDA/Au/l-Cys composites. 26888493 6 19 from enrichment 1072:1081 arg1 serum 1111:1115 human serum 1105:1115 human serum 1105:1115 In addition, the composites were successfully applied to the enrichment of glycopeptides from human serum and 40 unique N-glycosylation peptides from 31 different N-linked glycoproteins were identified. 26888493 7 20 theme glycoproteins 1290:1302 arg1 analysis 1278:1285 the analysis 1274:1285 the analysis of glycoproteins 1274:1302 The superior hydrophilic material is of great potential for the analysis of glycoproteins. 26888493 3 21 theme transmission 490:501 arg1 microscopy 512:521 transmission electron microscopy 490:521 transmission electron microscopy 490:521 The size, morphology, and composition of magG/PDA/Au/l-Cys composites were investigated by transmission electron microscopy, scanning electron microscopy, FT-infrared spectroscopy, and X-ray diffraction. 26888493 3 22 theme magG/PDA/Au/l-Cys 440:456 arg1 composites 458:467 magG/PDA/Au/l-Cys composites 440:467 magG/PDA/Au/l-Cys composites 440:467 The size, morphology, and composition of magG/PDA/Au/l-Cys composites were investigated by transmission electron microscopy, scanning electron microscopy, FT-infrared spectroscopy, and X-ray diffraction. 26888493 4 23 theme desirable 640:648 arg1 property 715:722 good biocompatibility easy separation property 677:722 good biocompatibility easy separation property 677:722 The composites possessed a number of desirable characteristics, including good biocompatibility easy separation property and excellent hydrophilicity. 26888493 4 23 theme desirable 640:648 arg1 hydrophilicity 738:751 excellent hydrophilicity 728:751 excellent hydrophilicity 728:751 The composites possessed a number of desirable characteristics, including good biocompatibility easy separation property and excellent hydrophilicity. 26888493 4 23 theme desirable 640:648 arg1 characteristics 650:664 desirable characteristics 640:664 desirable characteristics 640:664 The composites possessed a number of desirable characteristics, including good biocompatibility easy separation property and excellent hydrophilicity. 26888493 3 24 theme electron 503:510 arg1 microscopy 512:521 transmission electron microscopy 490:521 transmission electron microscopy 490:521 The size, morphology, and composition of magG/PDA/Au/l-Cys composites were investigated by transmission electron microscopy, scanning electron microscopy, FT-infrared spectroscopy, and X-ray diffraction. 26888493 0 25 theme selective 21:29 arg1 enrichment 31:40 Highly efficient and selective enrichment 0:40 Highly efficient and selective enrichment of glycopeptides 0:57 Highly efficient and selective enrichment of glycopeptides using easily synthesized magG/PDA/Au/l-Cys composites. 26888493 5 26 with enrichment 893:902 arg1 fmol 931:934 0.1 fmol 927:934 0.1 fmol 927:934 By virtue of the features contributed by different ingredients, the prepared composites demonstrated superior performance for glycopeptide enrichment with high sensitivity (0.1 fmol), efficiency, selectivity (1:100), and repeatability (at least ten times). 26888493 5 26 with enrichment 893:902 arg1 1:100 963:967 1:100 963:967 1:100 963:967 By virtue of the features contributed by different ingredients, the prepared composites demonstrated superior performance for glycopeptide enrichment with high sensitivity (0.1 fmol), efficiency, selectivity (1:100), and repeatability (at least ten times). 26888493 5 26 with enrichment 893:902 arg1 sensitivity 914:924 high sensitivity 909:924 high sensitivity (0.1 fmol) 909:935 By virtue of the features contributed by different ingredients, the prepared composites demonstrated superior performance for glycopeptide enrichment with high sensitivity (0.1 fmol), efficiency, selectivity (1:100), and repeatability (at least ten times). 26888493 5 26 with enrichment 893:902 arg1 times 1003:1007 at least ten times 990:1007 at least ten times 990:1007 By virtue of the features contributed by different ingredients, the prepared composites demonstrated superior performance for glycopeptide enrichment with high sensitivity (0.1 fmol), efficiency, selectivity (1:100), and repeatability (at least ten times). 26888493 5 26 with enrichment 893:902 arg1 efficiency 938:947 efficiency 938:947 efficiency 938:947 By virtue of the features contributed by different ingredients, the prepared composites demonstrated superior performance for glycopeptide enrichment with high sensitivity (0.1 fmol), efficiency, selectivity (1:100), and repeatability (at least ten times). 26888493 5 26 with enrichment 893:902 arg1 selectivity 950:960 selectivity 950:960 selectivity (1:100) 950:968 By virtue of the features contributed by different ingredients, the prepared composites demonstrated superior performance for glycopeptide enrichment with high sensitivity (0.1 fmol), efficiency, selectivity (1:100), and repeatability (at least ten times). 26888493 5 26 with enrichment 893:902 arg1 repeatability 975:987 repeatability 975:987 repeatability (at least ten times) 975:1008 By virtue of the features contributed by different ingredients, the prepared composites demonstrated superior performance for glycopeptide enrichment with high sensitivity (0.1 fmol), efficiency, selectivity (1:100), and repeatability (at least ten times). 26888493 1 27 theme selective 121:129 arg1 enrichment 145:154 Highly selective and efficient enrichment 114:154 Highly selective and efficient enrichment of glycopeptides from complex biological samples 114:203 Highly selective and efficient enrichment of glycopeptides from complex biological samples is necessary. 26888493 7 28 theme superior 1218:1225 arg1 material 1239:1246 The superior hydrophilic material 1214:1246 The superior hydrophilic material 1214:1246 The superior hydrophilic material is of great potential for the analysis of glycoproteins. 26888493 5 29 theme prepared 822:829 arg1 composites 831:840 the prepared composites 818:840 the prepared composites 818:840 By virtue of the features contributed by different ingredients, the prepared composites demonstrated superior performance for glycopeptide enrichment with high sensitivity (0.1 fmol), efficiency, selectivity (1:100), and repeatability (at least ten times). 26888493 4 30 theme characteristics 650:664 arg1 property 715:722 good biocompatibility easy separation property 677:722 good biocompatibility easy separation property 677:722 The composites possessed a number of desirable characteristics, including good biocompatibility easy separation property and excellent hydrophilicity. 26888493 4 30 theme characteristics 650:664 arg1 hydrophilicity 738:751 excellent hydrophilicity 728:751 excellent hydrophilicity 728:751 The composites possessed a number of desirable characteristics, including good biocompatibility easy separation property and excellent hydrophilicity. 26888493 4 30 theme characteristics 650:664 arg1 number 630:635 a number 628:635 a number of desirable characteristics, including good biocompatibility easy separation property and excellent hydrophilicity 628:751 The composites possessed a number of desirable characteristics, including good biocompatibility easy separation property and excellent hydrophilicity. 26888493 1 31 gly glycopeptides 159:171 arg2 glycopeptides 159:171 glycopeptides 159:171 glycopeptides 159:171 Highly selective and efficient enrichment of glycopeptides from complex biological samples is necessary. 26888493 2 32 theme magnetic 285:292 arg1 composites 303:312 novel zwitterionic hydrophilic polydopamine-coated magnetic graphene composites 234:312 novel zwitterionic hydrophilic polydopamine-coated magnetic graphene composites (magG/PDA/Au/l-Cys) 234:332 In this study, novel zwitterionic hydrophilic polydopamine-coated magnetic graphene composites (magG/PDA/Au/l-Cys) were synthesized and applied to the enrichment of glycopeptides. 26888493 2 32 theme magnetic 285:292 arg1 magG/PDA/Au/l-Cys 315:331 magG/PDA/Au/l-Cys 315:331 magG/PDA/Au/l-Cys 315:331 In this study, novel zwitterionic hydrophilic polydopamine-coated magnetic graphene composites (magG/PDA/Au/l-Cys) were synthesized and applied to the enrichment of glycopeptides. 26888493 6 33 theme different 1164:1172 arg1 glycoproteins 1183:1195 31 different N-linked glycoproteins 1161:1195 31 different N-linked glycoproteins 1161:1195 In addition, the composites were successfully applied to the enrichment of glycopeptides from human serum and 40 unique N-glycosylation peptides from 31 different N-linked glycoproteins were identified. 26888493 3 34 theme scanning 524:531 arg1 microscopy 542:551 scanning electron microscopy 524:551 scanning electron microscopy 524:551 The size, morphology, and composition of magG/PDA/Au/l-Cys composites were investigated by transmission electron microscopy, scanning electron microscopy, FT-infrared spectroscopy, and X-ray diffraction. 26888493 2 35 theme polydopamine-coated 265:283 arg1 composites 303:312 novel zwitterionic hydrophilic polydopamine-coated magnetic graphene composites 234:312 novel zwitterionic hydrophilic polydopamine-coated magnetic graphene composites (magG/PDA/Au/l-Cys) 234:332 In this study, novel zwitterionic hydrophilic polydopamine-coated magnetic graphene composites (magG/PDA/Au/l-Cys) were synthesized and applied to the enrichment of glycopeptides. 26888493 2 35 theme polydopamine-coated 265:283 arg1 magG/PDA/Au/l-Cys 315:331 magG/PDA/Au/l-Cys 315:331 magG/PDA/Au/l-Cys 315:331 In this study, novel zwitterionic hydrophilic polydopamine-coated magnetic graphene composites (magG/PDA/Au/l-Cys) were synthesized and applied to the enrichment of glycopeptides. 26888493 3 36 theme electron 533:540 arg1 microscopy 542:551 scanning electron microscopy 524:551 scanning electron microscopy 524:551 The size, morphology, and composition of magG/PDA/Au/l-Cys composites were investigated by transmission electron microscopy, scanning electron microscopy, FT-infrared spectroscopy, and X-ray diffraction. 26888493 3 37 theme composites 458:467 arg1 morphology 409:418 morphology 409:418 morphology 409:418 The size, morphology, and composition of magG/PDA/Au/l-Cys composites were investigated by transmission electron microscopy, scanning electron microscopy, FT-infrared spectroscopy, and X-ray diffraction. 26888493 3 37 theme composites 458:467 arg1 composition 425:435 composition 425:435 composition 425:435 The size, morphology, and composition of magG/PDA/Au/l-Cys composites were investigated by transmission electron microscopy, scanning electron microscopy, FT-infrared spectroscopy, and X-ray diffraction. 26888493 3 37 theme composites 458:467 arg1 size 403:406 size 403:406 size 403:406 The size, morphology, and composition of magG/PDA/Au/l-Cys composites were investigated by transmission electron microscopy, scanning electron microscopy, FT-infrared spectroscopy, and X-ray diffraction. 26888493 3 38 dep size 403:406 arg1 The 399:401 The 399:401 The 399:401 The size, morphology, and composition of magG/PDA/Au/l-Cys composites were investigated by transmission electron microscopy, scanning electron microscopy, FT-infrared spectroscopy, and X-ray diffraction. 26888493 2 39 theme hydrophilic 253:263 arg1 composites 303:312 novel zwitterionic hydrophilic polydopamine-coated magnetic graphene composites 234:312 novel zwitterionic hydrophilic polydopamine-coated magnetic graphene composites (magG/PDA/Au/l-Cys) 234:332 In this study, novel zwitterionic hydrophilic polydopamine-coated magnetic graphene composites (magG/PDA/Au/l-Cys) were synthesized and applied to the enrichment of glycopeptides. 26888493 2 39 theme hydrophilic 253:263 arg1 magG/PDA/Au/l-Cys 315:331 magG/PDA/Au/l-Cys 315:331 magG/PDA/Au/l-Cys 315:331 In this study, novel zwitterionic hydrophilic polydopamine-coated magnetic graphene composites (magG/PDA/Au/l-Cys) were synthesized and applied to the enrichment of glycopeptides. 26888493 1 40 theme efficient 135:143 arg1 enrichment 145:154 Highly selective and efficient enrichment 114:154 Highly selective and efficient enrichment of glycopeptides from complex biological samples 114:203 Highly selective and efficient enrichment of glycopeptides from complex biological samples is necessary. 26888493 0 41 theme glycopeptides 45:57 arg1 enrichment 31:40 Highly efficient and selective enrichment 0:40 Highly efficient and selective enrichment of glycopeptides 0:57 Highly efficient and selective enrichment of glycopeptides using easily synthesized magG/PDA/Au/l-Cys composites. 26888493 5 42 theme different 795:803 arg1 ingredients 805:815 different ingredients 795:815 different ingredients 795:815 By virtue of the features contributed by different ingredients, the prepared composites demonstrated superior performance for glycopeptide enrichment with high sensitivity (0.1 fmol), efficiency, selectivity (1:100), and repeatability (at least ten times). 26888493 2 43 theme novel 234:238 arg1 composites 303:312 novel zwitterionic hydrophilic polydopamine-coated magnetic graphene composites 234:312 novel zwitterionic hydrophilic polydopamine-coated magnetic graphene composites (magG/PDA/Au/l-Cys) 234:332 In this study, novel zwitterionic hydrophilic polydopamine-coated magnetic graphene composites (magG/PDA/Au/l-Cys) were synthesized and applied to the enrichment of glycopeptides. 26888493 2 43 theme novel 234:238 arg1 magG/PDA/Au/l-Cys 315:331 magG/PDA/Au/l-Cys 315:331 magG/PDA/Au/l-Cys 315:331 In this study, novel zwitterionic hydrophilic polydopamine-coated magnetic graphene composites (magG/PDA/Au/l-Cys) were synthesized and applied to the enrichment of glycopeptides. 26888493 2 44 theme zwitterionic 240:251 arg1 composites 303:312 novel zwitterionic hydrophilic polydopamine-coated magnetic graphene composites 234:312 novel zwitterionic hydrophilic polydopamine-coated magnetic graphene composites (magG/PDA/Au/l-Cys) 234:332 In this study, novel zwitterionic hydrophilic polydopamine-coated magnetic graphene composites (magG/PDA/Au/l-Cys) were synthesized and applied to the enrichment of glycopeptides. 26888493 2 44 theme zwitterionic 240:251 arg1 magG/PDA/Au/l-Cys 315:331 magG/PDA/Au/l-Cys 315:331 magG/PDA/Au/l-Cys 315:331 In this study, novel zwitterionic hydrophilic polydopamine-coated magnetic graphene composites (magG/PDA/Au/l-Cys) were synthesized and applied to the enrichment of glycopeptides. 26888493 7 45 theme hydrophilic 1227:1237 arg1 material 1239:1246 The superior hydrophilic material 1214:1246 The superior hydrophilic material 1214:1246 The superior hydrophilic material is of great potential for the analysis of glycoproteins. 26888493 6 46 gly glycopeptides 1086:1098 arg1 serum 1111:1115 human serum 1105:1115 human serum 1105:1115 In addition, the composites were successfully applied to the enrichment of glycopeptides from human serum and 40 unique N-glycosylation peptides from 31 different N-linked glycoproteins were identified. 26888493 6 46 gly glycopeptides 1086:1098 arg2 glycopeptides 1086:1098 glycopeptides 1086:1098 glycopeptides from human serum 1086:1115 In addition, the composites were successfully applied to the enrichment of glycopeptides from human serum and 40 unique N-glycosylation peptides from 31 different N-linked glycoproteins were identified. 26888493 2 47 theme glycopeptides 384:396 arg1 enrichment 370:379 the enrichment 366:379 the enrichment of glycopeptides 366:396 In this study, novel zwitterionic hydrophilic polydopamine-coated magnetic graphene composites (magG/PDA/Au/l-Cys) were synthesized and applied to the enrichment of glycopeptides. 26888493 5 48 gly glycopeptide 880:891 arg2 glycopeptide 880:891 glycopeptide enrichment 880:902 glycopeptide enrichment with high sensitivity (0.1 fmol), efficiency, selectivity (1:100), and repeatability (at least ten times) 880:1008 By virtue of the features contributed by different ingredients, the prepared composites demonstrated superior performance for glycopeptide enrichment with high sensitivity (0.1 fmol), efficiency, selectivity (1:100), and repeatability (at least ten times). 26888493 6 49 theme unique 1124:1129 arg1 peptides 1147:1154 40 unique N-glycosylation peptides 1121:1154 40 unique N-glycosylation peptides from 31 different N-linked glycoproteins 1121:1195 In addition, the composites were successfully applied to the enrichment of glycopeptides from human serum and 40 unique N-glycosylation peptides from 31 different N-linked glycoproteins were identified. 26888493 2 50 gly glycopeptides 384:396 arg2 glycopeptides 384:396 glycopeptides 384:396 glycopeptides 384:396 In this study, novel zwitterionic hydrophilic polydopamine-coated magnetic graphene composites (magG/PDA/Au/l-Cys) were synthesized and applied to the enrichment of glycopeptides. 26888493 7 51 gly glycoproteins 1290:1302 arg1 glycoproteins 1290:1302 glycoproteins 1290:1302 glycoproteins 1290:1302 The superior hydrophilic material is of great potential for the analysis of glycoproteins. 26888493 1 52 theme glycopeptides 159:171 arg1 enrichment 145:154 Highly selective and efficient enrichment 114:154 Highly selective and efficient enrichment of glycopeptides from complex biological samples 114:203 Highly selective and efficient enrichment of glycopeptides from complex biological samples is necessary. 26888493 3 53 theme FT-infrared 554:564 arg1 spectroscopy 566:577 FT-infrared spectroscopy 554:577 FT-infrared spectroscopy 554:577 The size, morphology, and composition of magG/PDA/Au/l-Cys composites were investigated by transmission electron microscopy, scanning electron microscopy, FT-infrared spectroscopy, and X-ray diffraction. 26888493 0 54 theme synthesized 72:82 arg1 composites 102:111 easily synthesized magG/PDA/Au/l-Cys composites 65:111 easily synthesized magG/PDA/Au/l-Cys composites 65:111 Highly efficient and selective enrichment of glycopeptides using easily synthesized magG/PDA/Au/l-Cys composites. 26888493 6 55 theme N-glycosylation 1131:1145 arg1 peptides 1147:1154 40 unique N-glycosylation peptides 1121:1154 40 unique N-glycosylation peptides from 31 different N-linked glycoproteins 1121:1195 In addition, the composites were successfully applied to the enrichment of glycopeptides from human serum and 40 unique N-glycosylation peptides from 31 different N-linked glycoproteins were identified. 26888493 0 56 gly glycopeptides 45:57 arg2 glycopeptides 45:57 glycopeptides 45:57 glycopeptides 45:57 Highly efficient and selective enrichment of glycopeptides using easily synthesized magG/PDA/Au/l-Cys composites. 26888493 4 57 theme excellent 728:736 arg1 hydrophilicity 738:751 excellent hydrophilicity 728:751 excellent hydrophilicity 728:751 The composites possessed a number of desirable characteristics, including good biocompatibility easy separation property and excellent hydrophilicity. 26888493 6 58 theme glycopeptides 1086:1098 arg1 enrichment 1072:1081 the enrichment 1068:1081 the enrichment of glycopeptides from human serum 1068:1115 In addition, the composites were successfully applied to the enrichment of glycopeptides from human serum and 40 unique N-glycosylation peptides from 31 different N-linked glycoproteins were identified. 26888493 6 59 link N-linked 1174:1181 arg1 glycoproteins 1183:1195 31 different N-linked glycoproteins 1161:1195 31 different N-linked glycoproteins 1161:1195 In addition, the composites were successfully applied to the enrichment of glycopeptides from human serum and 40 unique N-glycosylation peptides from 31 different N-linked glycoproteins were identified. 26888493 2 60 theme graphene 294:301 arg1 composites 303:312 novel zwitterionic hydrophilic polydopamine-coated magnetic graphene composites 234:312 novel zwitterionic hydrophilic polydopamine-coated magnetic graphene composites (magG/PDA/Au/l-Cys) 234:332 In this study, novel zwitterionic hydrophilic polydopamine-coated magnetic graphene composites (magG/PDA/Au/l-Cys) were synthesized and applied to the enrichment of glycopeptides. 26888493 2 60 theme graphene 294:301 arg1 magG/PDA/Au/l-Cys 315:331 magG/PDA/Au/l-Cys 315:331 magG/PDA/Au/l-Cys 315:331 In this study, novel zwitterionic hydrophilic polydopamine-coated magnetic graphene composites (magG/PDA/Au/l-Cys) were synthesized and applied to the enrichment of glycopeptides. 26888493 4 61 theme separation 704:713 arg1 property 715:722 good biocompatibility easy separation property 677:722 good biocompatibility easy separation property 677:722 The composites possessed a number of desirable characteristics, including good biocompatibility easy separation property and excellent hydrophilicity. 26888493 1 62 theme complex 178:184 arg1 samples 197:203 complex biological samples 178:203 complex biological samples 178:203 Highly selective and efficient enrichment of glycopeptides from complex biological samples is necessary. 25006806 0 0 theme first 53:57 arg1 compilation 92:102 a compilation 90:102 a compilation of glycan maps for a whole organism 90:138 Improved method for drawing of a glycan map, and the first page of glycan atlas, which is a compilation of glycan maps for a whole organism. 25006806 0 0 theme first 53:57 arg1 page 59:62 the first page 49:62 the first page of glycan atlas 49:78 Improved method for drawing of a glycan map, and the first page of glycan atlas, which is a compilation of glycan maps for a whole organism. 25006806 0 0 theme first 53:57 arg1 map 40:42 a glycan map 31:42 a glycan map 31:42 Improved method for drawing of a glycan map, and the first page of glycan atlas, which is a compilation of glycan maps for a whole organism. 25006806 8 1 theme mapping 1023:1029 arg1 tool 1076:1079 a powerful tool 1065:1079 a powerful tool for describing the micro-heterogeneity of the glycans 1065:1133 The comprehensive mapping method developed in this study is a powerful tool for describing the micro-heterogeneity of the glycans. 25006806 8 1 theme mapping 1023:1029 arg1 method 1031:1036 The comprehensive mapping method 1005:1036 The comprehensive mapping method developed in this study 1005:1060 The comprehensive mapping method developed in this study is a powerful tool for describing the micro-heterogeneity of the glycans. 25006806 7 2 theme monosaccharide 981:994 arg1 residue 996:1002 each monosaccharide residue 976:1002 each monosaccharide residue 976:1002 The adapted rule is that the elution time of pyridylamino glycans on high performance liquid chromatography (HPLC) is expected to be the simple sum of the partial elution times assigned to each monosaccharide residue. 25006806 7 3 theme performance 861:871 arg1 HPLC 896:899 HPLC 896:899 HPLC 896:899 The adapted rule is that the elution time of pyridylamino glycans on high performance liquid chromatography (HPLC) is expected to be the simple sum of the partial elution times assigned to each monosaccharide residue. 25006806 7 3 theme performance 861:871 arg1 chromatography 880:893 high performance liquid chromatography 856:893 high performance liquid chromatography (HPLC) 856:900 The adapted rule is that the elution time of pyridylamino glycans on high performance liquid chromatography (HPLC) is expected to be the simple sum of the partial elution times assigned to each monosaccharide residue. 25006806 2 4 theme structure 258:266 arg1 data 243:246 data 243:246 data of glycan structure and quantity 243:279 The glycan map that includes data of glycan structure and quantity displays micro-heterogeneity of the glycans in a tissue, an organ, or cells. 25006806 5 5 theme pyridylaminated 632:646 arg1 glycans 648:654 150 standard pyridylaminated glycans 619:654 150 standard pyridylaminated glycans 619:654 The mapping data of 150 standard pyridylaminated glycans were collected. 25006806 1 6 theme maps 173:176 arg1 Atlas 148:152 Glycan Atlas 141:152 Glycan Atlas 141:152 Glycan Atlas is a set of glycan maps over the whole body of an organism. 25006806 1 6 theme maps 173:176 arg1 set 159:161 a set 157:161 a set of glycan maps 157:176 Glycan Atlas is a set of glycan maps over the whole body of an organism. 25006806 1 6 theme maps 173:176 arg1 maps 173:176 glycan maps 166:176 glycan maps 166:176 Glycan Atlas is a set of glycan maps over the whole body of an organism. 25006806 8 7 theme comprehensive 1009:1021 arg1 tool 1076:1079 a powerful tool 1065:1079 a powerful tool for describing the micro-heterogeneity of the glycans 1065:1133 The comprehensive mapping method developed in this study is a powerful tool for describing the micro-heterogeneity of the glycans. 25006806 8 7 theme comprehensive 1009:1021 arg1 method 1031:1036 The comprehensive mapping method 1005:1036 The comprehensive mapping method developed in this study 1005:1060 The comprehensive mapping method developed in this study is a powerful tool for describing the micro-heterogeneity of the glycans. 25006806 9 8 theme pyridylamino 1164:1175 arg1 glycans 1183:1189 42 pyridylamino (PA-) glycans 1161:1189 42 pyridylamino (PA-) glycans 1161:1189 Furthermore, we prepared 42 pyridylamino (PA-) glycans from human serum and were able to draw the map of human serum N- and O-glycans as an initial step of Glycan Atlas editing. 25006806 7 9 theme elution 950:956 arg1 times 958:962 the partial elution times 938:962 the partial elution times assigned to each monosaccharide residue 938:1002 The adapted rule is that the elution time of pyridylamino glycans on high performance liquid chromatography (HPLC) is expected to be the simple sum of the partial elution times assigned to each monosaccharide residue. 25006806 2 10 theme glycan 251:256 arg1 structure 258:266 glycan structure 251:266 glycan structure 251:266 The glycan map that includes data of glycan structure and quantity displays micro-heterogeneity of the glycans in a tissue, an organ, or cells. 25006806 2 11 from organ 341:345 arg1 micro-heterogeneity 290:308 micro-heterogeneity 290:308 micro-heterogeneity of the glycans in a tissue, an organ, or cells 290:355 The glycan map that includes data of glycan structure and quantity displays micro-heterogeneity of the glycans in a tissue, an organ, or cells. 25006806 3 12 theme N-linked 434:441 arg1 oligosaccharides 443:458 N-linked oligosaccharides 434:458 N-linked oligosaccharides on glycoproteins 434:475 The two-dimensional glycan mapping is widely used for structure analysis of N-linked oligosaccharides on glycoproteins. 25006806 3 13 from oligosaccharides 443:458 arg1 glycoproteins 463:475 glycoproteins 463:475 glycoproteins 463:475 The two-dimensional glycan mapping is widely used for structure analysis of N-linked oligosaccharides on glycoproteins. 25006806 0 14 theme page 59:62 arg1 method 9:14 Improved method 0:14 Improved method for drawing of a glycan map, and the first page of glycan atlas, which is a compilation of glycan maps for a whole organism. 0:139 Improved method for drawing of a glycan map, and the first page of glycan atlas, which is a compilation of glycan maps for a whole organism. 25006806 2 15 from cells 351:355 arg1 micro-heterogeneity 290:308 micro-heterogeneity 290:308 micro-heterogeneity of the glycans in a tissue, an organ, or cells 290:355 The glycan map that includes data of glycan structure and quantity displays micro-heterogeneity of the glycans in a tissue, an organ, or cells. 25006806 0 16 theme whole 125:129 arg1 organism 131:138 a whole organism 123:138 a whole organism 123:138 Improved method for drawing of a glycan map, and the first page of glycan atlas, which is a compilation of glycan maps for a whole organism. 25006806 3 17 theme oligosaccharides 443:458 arg1 analysis 422:429 structure analysis 412:429 structure analysis of N-linked oligosaccharides on glycoproteins 412:475 The two-dimensional glycan mapping is widely used for structure analysis of N-linked oligosaccharides on glycoproteins. 25006806 1 18 theme whole 187:191 arg1 body 193:196 the whole body 183:196 the whole body of an organism 183:211 Glycan Atlas is a set of glycan maps over the whole body of an organism. 25006806 0 19 theme atlas 74:78 arg1 compilation 92:102 a compilation 90:102 a compilation of glycan maps for a whole organism 90:138 Improved method for drawing of a glycan map, and the first page of glycan atlas, which is a compilation of glycan maps for a whole organism. 25006806 0 19 theme atlas 74:78 arg1 page 59:62 the first page 49:62 the first page of glycan atlas 49:78 Improved method for drawing of a glycan map, and the first page of glycan atlas, which is a compilation of glycan maps for a whole organism. 25006806 0 19 theme atlas 74:78 arg1 map 40:42 a glycan map 31:42 a glycan map 31:42 Improved method for drawing of a glycan map, and the first page of glycan atlas, which is a compilation of glycan maps for a whole organism. 25006806 7 20 theme times 958:962 arg1 sum 931:933 the simple sum 920:933 the simple sum of the partial elution times assigned to each monosaccharide residue 920:1002 The adapted rule is that the elution time of pyridylamino glycans on high performance liquid chromatography (HPLC) is expected to be the simple sum of the partial elution times assigned to each monosaccharide residue. 25006806 7 20 theme times 958:962 arg1 time 824:827 the elution time 812:827 the elution time of pyridylamino glycans on high performance liquid chromatography (HPLC) 812:900 The adapted rule is that the elution time of pyridylamino glycans on high performance liquid chromatography (HPLC) is expected to be the simple sum of the partial elution times assigned to each monosaccharide residue. 25006806 7 21 theme pyridylamino 832:843 arg1 glycans 845:851 pyridylamino glycans 832:851 pyridylamino glycans 832:851 The adapted rule is that the elution time of pyridylamino glycans on high performance liquid chromatography (HPLC) is expected to be the simple sum of the partial elution times assigned to each monosaccharide residue. 25006806 0 22 theme glycan 67:72 arg1 atlas 74:78 glycan atlas 67:78 glycan atlas 67:78 Improved method for drawing of a glycan map, and the first page of glycan atlas, which is a compilation of glycan maps for a whole organism. 25006806 6 23 theme glycan 775:780 arg1 map 782:784 this extended glycan map 761:784 this extended glycan map 761:784 The empirical additivity rule which was proposed in former reports was able to adapt for this extended glycan map. 25006806 7 24 theme elution 816:822 arg1 sum 931:933 the simple sum 920:933 the simple sum of the partial elution times assigned to each monosaccharide residue 920:1002 The adapted rule is that the elution time of pyridylamino glycans on high performance liquid chromatography (HPLC) is expected to be the simple sum of the partial elution times assigned to each monosaccharide residue. 25006806 7 24 theme elution 816:822 arg1 time 824:827 the elution time 812:827 the elution time of pyridylamino glycans on high performance liquid chromatography (HPLC) 812:900 The adapted rule is that the elution time of pyridylamino glycans on high performance liquid chromatography (HPLC) is expected to be the simple sum of the partial elution times assigned to each monosaccharide residue. 25006806 3 25 link N-linked 434:441 arg1 oligosaccharides 443:458 N-linked oligosaccharides 434:458 N-linked oligosaccharides on glycoproteins 434:475 The two-dimensional glycan mapping is widely used for structure analysis of N-linked oligosaccharides on glycoproteins. 25006806 6 26 theme extended 766:773 arg1 map 782:784 this extended glycan map 761:784 this extended glycan map 761:784 The empirical additivity rule which was proposed in former reports was able to adapt for this extended glycan map. 25006806 7 27 theme partial 942:948 arg1 times 958:962 the partial elution times 938:962 the partial elution times assigned to each monosaccharide residue 938:1002 The adapted rule is that the elution time of pyridylamino glycans on high performance liquid chromatography (HPLC) is expected to be the simple sum of the partial elution times assigned to each monosaccharide residue. 25006806 6 28 theme additivity 686:695 arg1 able 743:746 able 743:746 able 743:746 The empirical additivity rule which was proposed in former reports was able to adapt for this extended glycan map. 25006806 6 28 theme additivity 686:695 arg1 rule 697:700 The empirical additivity rule 672:700 The empirical additivity rule which was proposed in former reports 672:737 The empirical additivity rule which was proposed in former reports was able to adapt for this extended glycan map. 25006806 8 29 theme glycans 1127:1133 arg1 micro-heterogeneity 1100:1118 the micro-heterogeneity 1096:1118 the micro-heterogeneity of the glycans 1096:1133 The comprehensive mapping method developed in this study is a powerful tool for describing the micro-heterogeneity of the glycans. 25006806 0 30 theme Improved 0:7 arg1 method 9:14 Improved method 0:14 Improved method for drawing of a glycan map, and the first page of glycan atlas, which is a compilation of glycan maps for a whole organism. 0:139 Improved method for drawing of a glycan map, and the first page of glycan atlas, which is a compilation of glycan maps for a whole organism. 25006806 9 31 theme human 1196:1200 arg1 serum 1202:1206 human serum 1196:1206 human serum 1196:1206 Furthermore, we prepared 42 pyridylamino (PA-) glycans from human serum and were able to draw the map of human serum N- and O-glycans as an initial step of Glycan Atlas editing. 25006806 2 32 gly micro-heterogeneity 290:308 arg1 glycans 317:323 the glycans 313:323 the glycans in a tissue, an organ, or cells 313:355 The glycan map that includes data of glycan structure and quantity displays micro-heterogeneity of the glycans in a tissue, an organ, or cells. 25006806 6 33 theme empirical 676:684 arg1 able 743:746 able 743:746 able 743:746 The empirical additivity rule which was proposed in former reports was able to adapt for this extended glycan map. 25006806 6 33 theme empirical 676:684 arg1 rule 697:700 The empirical additivity rule 672:700 The empirical additivity rule which was proposed in former reports 672:737 The empirical additivity rule which was proposed in former reports was able to adapt for this extended glycan map. 25006806 2 34 theme glycan 218:223 arg1 map 225:227 The glycan map 214:227 The glycan map that includes data of glycan structure and quantity 214:279 The glycan map that includes data of glycan structure and quantity displays micro-heterogeneity of the glycans in a tissue, an organ, or cells. 25006806 4 35 theme O-glycans 559:567 arg1 mapping 536:542 the mapping 532:542 the mapping of both N- and O-glycans with and without sialic acid 532:596 In this study we developed a comprehensive method for the mapping of both N- and O-glycans with and without sialic acid. 25006806 8 36 theme powerful 1067:1074 arg1 method 1031:1036 The comprehensive mapping method 1005:1036 The comprehensive mapping method developed in this study 1005:1060 The comprehensive mapping method developed in this study is a powerful tool for describing the micro-heterogeneity of the glycans. 25006806 8 36 theme powerful 1067:1074 arg1 tool 1076:1079 a powerful tool 1065:1079 a powerful tool for describing the micro-heterogeneity of the glycans 1065:1133 The comprehensive mapping method developed in this study is a powerful tool for describing the micro-heterogeneity of the glycans. 25006806 7 37 theme glycans 845:851 arg1 sum 931:933 the simple sum 920:933 the simple sum of the partial elution times assigned to each monosaccharide residue 920:1002 The adapted rule is that the elution time of pyridylamino glycans on high performance liquid chromatography (HPLC) is expected to be the simple sum of the partial elution times assigned to each monosaccharide residue. 25006806 7 37 theme glycans 845:851 arg1 time 824:827 the elution time 812:827 the elution time of pyridylamino glycans on high performance liquid chromatography (HPLC) 812:900 The adapted rule is that the elution time of pyridylamino glycans on high performance liquid chromatography (HPLC) is expected to be the simple sum of the partial elution times assigned to each monosaccharide residue. 25006806 9 38 theme Glycan 1292:1297 arg1 editing 1305:1311 Glycan Atlas editing 1292:1311 Glycan Atlas editing 1292:1311 Furthermore, we prepared 42 pyridylamino (PA-) glycans from human serum and were able to draw the map of human serum N- and O-glycans as an initial step of Glycan Atlas editing. 25006806 7 39 theme simple 924:929 arg1 sum 931:933 the simple sum 920:933 the simple sum of the partial elution times assigned to each monosaccharide residue 920:1002 The adapted rule is that the elution time of pyridylamino glycans on high performance liquid chromatography (HPLC) is expected to be the simple sum of the partial elution times assigned to each monosaccharide residue. 25006806 7 39 theme simple 924:929 arg1 time 824:827 the elution time 812:827 the elution time of pyridylamino glycans on high performance liquid chromatography (HPLC) 812:900 The adapted rule is that the elution time of pyridylamino glycans on high performance liquid chromatography (HPLC) is expected to be the simple sum of the partial elution times assigned to each monosaccharide residue. 25006806 7 40 theme high 856:859 arg1 HPLC 896:899 HPLC 896:899 HPLC 896:899 The adapted rule is that the elution time of pyridylamino glycans on high performance liquid chromatography (HPLC) is expected to be the simple sum of the partial elution times assigned to each monosaccharide residue. 25006806 7 40 theme high 856:859 arg1 chromatography 880:893 high performance liquid chromatography 856:893 high performance liquid chromatography (HPLC) 856:900 The adapted rule is that the elution time of pyridylamino glycans on high performance liquid chromatography (HPLC) is expected to be the simple sum of the partial elution times assigned to each monosaccharide residue. 25006806 8 41 gly micro-heterogeneity 1100:1118 arg1 glycans 1127:1133 the glycans 1123:1133 the glycans 1123:1133 The comprehensive mapping method developed in this study is a powerful tool for describing the micro-heterogeneity of the glycans. 25006806 4 42 theme sialic 586:591 arg1 acid 593:596 sialic acid 586:596 sialic acid 586:596 In this study we developed a comprehensive method for the mapping of both N- and O-glycans with and without sialic acid. 25006806 1 43 theme Glycan 141:146 arg1 Atlas 148:152 Glycan Atlas 141:152 Glycan Atlas 141:152 Glycan Atlas is a set of glycan maps over the whole body of an organism. 25006806 1 43 theme Glycan 141:146 arg1 set 159:161 a set 157:161 a set of glycan maps 157:176 Glycan Atlas is a set of glycan maps over the whole body of an organism. 25006806 1 43 theme Glycan 141:146 arg1 maps 173:176 glycan maps 166:176 glycan maps 166:176 Glycan Atlas is a set of glycan maps over the whole body of an organism. 25006806 1 44 theme organism 204:211 arg1 body 193:196 the whole body 183:196 the whole body of an organism 183:211 Glycan Atlas is a set of glycan maps over the whole body of an organism. 25006806 5 45 theme mapping 603:609 arg1 data 611:614 The mapping data 599:614 The mapping data of 150 standard pyridylaminated glycans 599:654 The mapping data of 150 standard pyridylaminated glycans were collected. 25006806 9 46 dep serum 1247:1251 arg1 O-glycans 1260:1268 O-glycans 1260:1268 O-glycans 1260:1268 Furthermore, we prepared 42 pyridylamino (PA-) glycans from human serum and were able to draw the map of human serum N- and O-glycans as an initial step of Glycan Atlas editing. 25006806 9 46 dep serum 1247:1251 arg1 N- 1253:1254 N- 1253:1254 N- 1253:1254 Furthermore, we prepared 42 pyridylamino (PA-) glycans from human serum and were able to draw the map of human serum N- and O-glycans as an initial step of Glycan Atlas editing. 25006806 7 47 theme adapted 791:797 arg1 rule 799:802 The adapted rule 787:802 The adapted rule 787:802 The adapted rule is that the elution time of pyridylamino glycans on high performance liquid chromatography (HPLC) is expected to be the simple sum of the partial elution times assigned to each monosaccharide residue. 25006806 9 48 theme editing 1305:1311 arg1 step 1284:1287 an initial step 1273:1287 an initial step of Glycan Atlas editing 1273:1311 Furthermore, we prepared 42 pyridylamino (PA-) glycans from human serum and were able to draw the map of human serum N- and O-glycans as an initial step of Glycan Atlas editing. 25006806 9 48 theme editing 1305:1311 arg1 map 1234:1236 the map 1230:1236 the map of human serum N- and O-glycans 1230:1268 Furthermore, we prepared 42 pyridylamino (PA-) glycans from human serum and were able to draw the map of human serum N- and O-glycans as an initial step of Glycan Atlas editing. 25006806 9 49 theme human 1241:1245 arg1 serum 1247:1251 human serum N- and O-glycans 1241:1268 human serum N- and O-glycans 1241:1268 Furthermore, we prepared 42 pyridylamino (PA-) glycans from human serum and were able to draw the map of human serum N- and O-glycans as an initial step of Glycan Atlas editing. 25006806 2 50 from micro-heterogeneity 290:308 arg1 organ 341:345 an organ 338:345 an organ 338:345 The glycan map that includes data of glycan structure and quantity displays micro-heterogeneity of the glycans in a tissue, an organ, or cells. 25006806 2 50 from micro-heterogeneity 290:308 arg1 cells 351:355 cells 351:355 cells 351:355 The glycan map that includes data of glycan structure and quantity displays micro-heterogeneity of the glycans in a tissue, an organ, or cells. 25006806 2 50 from micro-heterogeneity 290:308 arg1 tissue 330:335 a tissue 328:335 a tissue 328:335 The glycan map that includes data of glycan structure and quantity displays micro-heterogeneity of the glycans in a tissue, an organ, or cells. 25006806 2 51 theme glycans 317:323 arg1 micro-heterogeneity 290:308 micro-heterogeneity 290:308 micro-heterogeneity of the glycans in a tissue, an organ, or cells 290:355 The glycan map that includes data of glycan structure and quantity displays micro-heterogeneity of the glycans in a tissue, an organ, or cells. 25006806 0 52 theme map 40:42 arg1 method 9:14 Improved method 0:14 Improved method for drawing of a glycan map, and the first page of glycan atlas, which is a compilation of glycan maps for a whole organism. 0:139 Improved method for drawing of a glycan map, and the first page of glycan atlas, which is a compilation of glycan maps for a whole organism. 25006806 9 53 theme initial 1276:1282 arg1 step 1284:1287 an initial step 1273:1287 an initial step of Glycan Atlas editing 1273:1311 Furthermore, we prepared 42 pyridylamino (PA-) glycans from human serum and were able to draw the map of human serum N- and O-glycans as an initial step of Glycan Atlas editing. 25006806 9 53 theme initial 1276:1282 arg1 map 1234:1236 the map 1230:1236 the map of human serum N- and O-glycans 1230:1268 Furthermore, we prepared 42 pyridylamino (PA-) glycans from human serum and were able to draw the map of human serum N- and O-glycans as an initial step of Glycan Atlas editing. 25006806 0 54 theme glycan 33:38 arg1 page 59:62 the first page 49:62 the first page of glycan atlas 49:78 Improved method for drawing of a glycan map, and the first page of glycan atlas, which is a compilation of glycan maps for a whole organism. 25006806 0 54 theme glycan 33:38 arg1 compilation 92:102 a compilation 90:102 a compilation of glycan maps for a whole organism 90:138 Improved method for drawing of a glycan map, and the first page of glycan atlas, which is a compilation of glycan maps for a whole organism. 25006806 0 54 theme glycan 33:38 arg1 map 40:42 a glycan map 31:42 a glycan map 31:42 Improved method for drawing of a glycan map, and the first page of glycan atlas, which is a compilation of glycan maps for a whole organism. 25006806 9 55 theme Atlas 1299:1303 arg1 editing 1305:1311 Glycan Atlas editing 1292:1311 Glycan Atlas editing 1292:1311 Furthermore, we prepared 42 pyridylamino (PA-) glycans from human serum and were able to draw the map of human serum N- and O-glycans as an initial step of Glycan Atlas editing. 25006806 7 56 from time 824:827 arg1 HPLC 896:899 HPLC 896:899 HPLC 896:899 The adapted rule is that the elution time of pyridylamino glycans on high performance liquid chromatography (HPLC) is expected to be the simple sum of the partial elution times assigned to each monosaccharide residue. 25006806 7 56 from time 824:827 arg1 chromatography 880:893 high performance liquid chromatography 856:893 high performance liquid chromatography (HPLC) 856:900 The adapted rule is that the elution time of pyridylamino glycans on high performance liquid chromatography (HPLC) is expected to be the simple sum of the partial elution times assigned to each monosaccharide residue. 25006806 0 57 theme maps 114:117 arg1 page 59:62 the first page 49:62 the first page of glycan atlas 49:78 Improved method for drawing of a glycan map, and the first page of glycan atlas, which is a compilation of glycan maps for a whole organism. 25006806 0 57 theme maps 114:117 arg1 compilation 92:102 a compilation 90:102 a compilation of glycan maps for a whole organism 90:138 Improved method for drawing of a glycan map, and the first page of glycan atlas, which is a compilation of glycan maps for a whole organism. 25006806 0 57 theme maps 114:117 arg1 map 40:42 a glycan map 31:42 a glycan map 31:42 Improved method for drawing of a glycan map, and the first page of glycan atlas, which is a compilation of glycan maps for a whole organism. 25006806 3 58 used used 403:406 arg2 mapping 385:391 The two-dimensional glycan mapping 358:391 The two-dimensional glycan mapping 358:391 The two-dimensional glycan mapping is widely used for structure analysis of N-linked oligosaccharides on glycoproteins. 25006806 3 59 gly glycoproteins 463:475 arg1 glycoproteins 463:475 glycoproteins 463:475 glycoproteins 463:475 The two-dimensional glycan mapping is widely used for structure analysis of N-linked oligosaccharides on glycoproteins. 25006806 3 60 from glycoproteins 463:475 arg1 analysis 422:429 structure analysis 412:429 structure analysis of N-linked oligosaccharides on glycoproteins 412:475 The two-dimensional glycan mapping is widely used for structure analysis of N-linked oligosaccharides on glycoproteins. 25006806 4 61 theme comprehensive 507:519 arg1 method 521:526 a comprehensive method 505:526 a comprehensive method for the mapping of both N- and O-glycans with and without sialic acid 505:596 In this study we developed a comprehensive method for the mapping of both N- and O-glycans with and without sialic acid. 25006806 0 62 theme glycan 107:112 arg1 maps 114:117 glycan maps 107:117 glycan maps for a whole organism 107:138 Improved method for drawing of a glycan map, and the first page of glycan atlas, which is a compilation of glycan maps for a whole organism. 25006806 7 63 theme liquid 873:878 arg1 HPLC 896:899 HPLC 896:899 HPLC 896:899 The adapted rule is that the elution time of pyridylamino glycans on high performance liquid chromatography (HPLC) is expected to be the simple sum of the partial elution times assigned to each monosaccharide residue. 25006806 7 63 theme liquid 873:878 arg1 chromatography 880:893 high performance liquid chromatography 856:893 high performance liquid chromatography (HPLC) 856:900 The adapted rule is that the elution time of pyridylamino glycans on high performance liquid chromatography (HPLC) is expected to be the simple sum of the partial elution times assigned to each monosaccharide residue. 25006806 3 64 theme glycan 378:383 arg1 mapping 385:391 The two-dimensional glycan mapping 358:391 The two-dimensional glycan mapping 358:391 The two-dimensional glycan mapping is widely used for structure analysis of N-linked oligosaccharides on glycoproteins. 25006806 3 65 theme two-dimensional 362:376 arg1 mapping 385:391 The two-dimensional glycan mapping 358:391 The two-dimensional glycan mapping 358:391 The two-dimensional glycan mapping is widely used for structure analysis of N-linked oligosaccharides on glycoproteins. 25006806 5 66 theme glycans 648:654 arg1 data 611:614 The mapping data 599:614 The mapping data of 150 standard pyridylaminated glycans 599:654 The mapping data of 150 standard pyridylaminated glycans were collected. 25006806 5 67 theme standard 623:630 arg1 glycans 648:654 150 standard pyridylaminated glycans 619:654 150 standard pyridylaminated glycans 619:654 The mapping data of 150 standard pyridylaminated glycans were collected. 25006806 2 68 from glycans 317:323 arg1 organ 341:345 an organ 338:345 an organ 338:345 The glycan map that includes data of glycan structure and quantity displays micro-heterogeneity of the glycans in a tissue, an organ, or cells. 25006806 2 68 from glycans 317:323 arg1 cells 351:355 cells 351:355 cells 351:355 The glycan map that includes data of glycan structure and quantity displays micro-heterogeneity of the glycans in a tissue, an organ, or cells. 25006806 2 68 from glycans 317:323 arg1 tissue 330:335 a tissue 328:335 a tissue 328:335 The glycan map that includes data of glycan structure and quantity displays micro-heterogeneity of the glycans in a tissue, an organ, or cells. 25006806 2 69 theme quantity 272:279 arg1 data 243:246 data 243:246 data of glycan structure and quantity 243:279 The glycan map that includes data of glycan structure and quantity displays micro-heterogeneity of the glycans in a tissue, an organ, or cells. 25006806 4 70 theme N- 552:553 arg1 mapping 536:542 the mapping 532:542 the mapping of both N- and O-glycans with and without sialic acid 532:596 In this study we developed a comprehensive method for the mapping of both N- and O-glycans with and without sialic acid. 25006806 6 71 theme former 724:729 arg1 reports 731:737 former reports 724:737 former reports 724:737 The empirical additivity rule which was proposed in former reports was able to adapt for this extended glycan map. 25006806 9 72 theme serum 1247:1251 arg1 step 1284:1287 an initial step 1273:1287 an initial step of Glycan Atlas editing 1273:1311 Furthermore, we prepared 42 pyridylamino (PA-) glycans from human serum and were able to draw the map of human serum N- and O-glycans as an initial step of Glycan Atlas editing. 25006806 9 72 theme serum 1247:1251 arg1 map 1234:1236 the map 1230:1236 the map of human serum N- and O-glycans 1230:1268 Furthermore, we prepared 42 pyridylamino (PA-) glycans from human serum and were able to draw the map of human serum N- and O-glycans as an initial step of Glycan Atlas editing. 25006806 2 73 from tissue 330:335 arg1 micro-heterogeneity 290:308 micro-heterogeneity 290:308 micro-heterogeneity of the glycans in a tissue, an organ, or cells 290:355 The glycan map that includes data of glycan structure and quantity displays micro-heterogeneity of the glycans in a tissue, an organ, or cells. 25006806 3 74 theme structure 412:420 arg1 analysis 422:429 structure analysis 412:429 structure analysis of N-linked oligosaccharides on glycoproteins 412:475 The two-dimensional glycan mapping is widely used for structure analysis of N-linked oligosaccharides on glycoproteins. 25006806 3 75 from analysis 422:429 arg1 glycoproteins 463:475 glycoproteins 463:475 glycoproteins 463:475 The two-dimensional glycan mapping is widely used for structure analysis of N-linked oligosaccharides on glycoproteins. 25006806 1 76 theme glycan 166:171 arg1 maps 173:176 glycan maps 166:176 glycan maps 166:176 Glycan Atlas is a set of glycan maps over the whole body of an organism. 24994967 10 0 from role 1521:1524 arg1 maintenance 1559:1569 the maintenance 1555:1569 the maintenance of oral health and homeostasis 1555:1600 This study reveals the important role of salivary glycoproteins in the maintenance of oral health and homeostasis and the great potential of saliva for biomarker discovery and disease diagnosis. 24994967 10 1 theme saliva 1629:1634 arg1 potential 1616:1624 the great potential 1606:1624 the great potential of saliva for biomarker discovery and disease diagnosis 1606:1680 This study reveals the important role of salivary glycoproteins in the maintenance of oral health and homeostasis and the great potential of saliva for biomarker discovery and disease diagnosis. 24994967 10 1 theme saliva 1629:1634 arg1 role 1521:1524 the important role 1507:1524 the important role of salivary glycoproteins in the maintenance of oral health and homeostasis 1507:1600 This study reveals the important role of salivary glycoproteins in the maintenance of oral health and homeostasis and the great potential of saliva for biomarker discovery and disease diagnosis. 24994967 1 2 theme great 161:165 arg1 potential 167:175 great potential 161:175 great potential for biomarker discovery and disease diagnosis 161:221 BACKGROUND Glycoproteins comprise a large portion of the salivary proteome and have great potential for biomarker discovery and disease diagnosis. 24994967 8 3 theme potential 1225:1233 arg1 age- 1235:1238 potential age- 1225:1238 potential age- 1225:1238 Fifteen salivary glycoproteins were identified as potential age- or gender-associated glycoproteins, and many of them have functions related to innate immunity against microorganisms and oral cavity protection. 24994967 8 3 theme potential 1225:1233 arg1 glycoproteins 1192:1204 Fifteen salivary glycoproteins 1175:1204 Fifteen salivary glycoproteins 1175:1204 Fifteen salivary glycoproteins were identified as potential age- or gender-associated glycoproteins, and many of them have functions related to innate immunity against microorganisms and oral cavity protection. 24994967 1 4 contain have 156:159 arg1 Glycoproteins 88:100 BACKGROUND Glycoproteins 77:100 BACKGROUND Glycoproteins 77:100 BACKGROUND Glycoproteins comprise a large portion of the salivary proteome and have great potential for biomarker discovery and disease diagnosis. 24994967 1 4 contain have 156:159 arg2 potential 167:175 great potential 161:175 great potential for biomarker discovery and disease diagnosis 161:221 BACKGROUND Glycoproteins comprise a large portion of the salivary proteome and have great potential for biomarker discovery and disease diagnosis. 24994967 8 5 theme related 1308:1314 arg1 functions 1298:1306 functions 1298:1306 functions related to innate immunity against microorganisms and oral cavity protection 1298:1383 Fifteen salivary glycoproteins were identified as potential age- or gender-associated glycoproteins, and many of them have functions related to innate immunity against microorganisms and oral cavity protection. 24994967 8 5 theme related 1308:1314 arg1 glycoproteins 1261:1273 gender-associated glycoproteins 1243:1273 gender-associated glycoproteins 1243:1273 Fifteen salivary glycoproteins were identified as potential age- or gender-associated glycoproteins, and many of them have functions related to innate immunity against microorganisms and oral cavity protection. 24994967 8 5 theme related 1308:1314 arg1 glycoproteins 1192:1204 Fifteen salivary glycoproteins 1175:1204 Fifteen salivary glycoproteins 1175:1204 Fifteen salivary glycoproteins were identified as potential age- or gender-associated glycoproteins, and many of them have functions related to innate immunity against microorganisms and oral cavity protection. 24994967 5 6 theme groups 891:896 arg1 glycoproteomes 848:861 the salivary glycoproteomes 835:861 the salivary glycoproteomes of different age and gender groups 835:896 Selected physiochemical characteristics of salivary glycoproteins were analyzed, and the salivary glycoproteomes of different age and gender groups were compared based on their glycoprotein components and gene ontology. 24994967 8 7 theme innate 1319:1324 arg1 immunity 1326:1333 innate immunity 1319:1333 innate immunity against microorganisms 1319:1356 Fifteen salivary glycoproteins were identified as potential age- or gender-associated glycoproteins, and many of them have functions related to innate immunity against microorganisms and oral cavity protection. 24994967 7 8 theme salivary 1130:1137 arg1 N-glycoproteins 1139:1153 salivary N-glycoproteins 1130:1153 salivary N-glycoproteins 1130:1153 The numbers of salivary N-glycoproteins increased with age. 24994967 1 9 theme biomarker 181:189 arg1 discovery 191:199 biomarker discovery 181:199 biomarker discovery 181:199 BACKGROUND Glycoproteins comprise a large portion of the salivary proteome and have great potential for biomarker discovery and disease diagnosis. 24994967 2 10 theme saliva 287:292 arg1 concentration 264:276 the concentration 260:276 the concentration of whole saliva 260:292 However, the rate of production and the concentration of whole saliva change with age, gender and physiological states of the human body. 24994967 2 10 theme saliva 287:292 arg1 rate 237:240 the rate 233:240 the rate of production 233:254 However, the rate of production and the concentration of whole saliva change with age, gender and physiological states of the human body. 24994967 5 11 theme different 866:874 arg1 groups 891:896 different age and gender groups 866:896 different age and gender groups 866:896 Selected physiochemical characteristics of salivary glycoproteins were analyzed, and the salivary glycoproteomes of different age and gender groups were compared based on their glycoprotein components and gene ontology. 24994967 2 12 theme body 356:359 arg1 gender 311:316 gender 311:316 gender 311:316 However, the rate of production and the concentration of whole saliva change with age, gender and physiological states of the human body. 24994967 2 12 theme body 356:359 arg1 states 336:341 physiological states 322:341 physiological states of the human body 322:359 However, the rate of production and the concentration of whole saliva change with age, gender and physiological states of the human body. 24994967 2 12 theme body 356:359 arg1 age 306:308 age 306:308 age 306:308 However, the rate of production and the concentration of whole saliva change with age, gender and physiological states of the human body. 24994967 8 13 contain have 1293:1296 arg2 functions 1298:1306 functions 1298:1306 functions related to innate immunity against microorganisms and oral cavity protection 1298:1383 Fifteen salivary glycoproteins were identified as potential age- or gender-associated glycoproteins, and many of them have functions related to innate immunity against microorganisms and oral cavity protection. 24994967 8 13 contain have 1293:1296 arg1 them 1288:1291 them 1288:1291 them 1288:1291 Fifteen salivary glycoproteins were identified as potential age- or gender-associated glycoproteins, and many of them have functions related to innate immunity against microorganisms and oral cavity protection. 24994967 8 13 contain have 1293:1296 arg2 glycoproteins 1261:1273 gender-associated glycoproteins 1243:1273 gender-associated glycoproteins 1243:1273 Fifteen salivary glycoproteins were identified as potential age- or gender-associated glycoproteins, and many of them have functions related to innate immunity against microorganisms and oral cavity protection. 24994967 8 13 contain have 1293:1296 arg1 many 1280:1283 many 1280:1283 many 1280:1283 Fifteen salivary glycoproteins were identified as potential age- or gender-associated glycoproteins, and many of them have functions related to innate immunity against microorganisms and oral cavity protection. 24994967 8 13 contain have 1293:1296 arg2 glycoproteins 1192:1204 Fifteen salivary glycoproteins 1175:1204 Fifteen salivary glycoproteins 1175:1204 Fifteen salivary glycoproteins were identified as potential age- or gender-associated glycoproteins, and many of them have functions related to innate immunity against microorganisms and oral cavity protection. 24994967 8 14 theme cavity 1367:1372 arg1 protection 1374:1383 oral cavity protection 1362:1383 oral cavity protection 1362:1383 Fifteen salivary glycoproteins were identified as potential age- or gender-associated glycoproteins, and many of them have functions related to innate immunity against microorganisms and oral cavity protection. 24994967 5 15 gly glycoprotein 927:938 arg1 glycoprotein 927:938 their glycoprotein components 921:949 their glycoprotein components 921:949 Selected physiochemical characteristics of salivary glycoproteins were analyzed, and the salivary glycoproteomes of different age and gender groups were compared based on their glycoprotein components and gene ontology. 24994967 4 16 theme mass 716:719 arg1 identification 734:747 mass spectrometry identification 716:747 mass spectrometry identification 716:747 METHODS Formerly N-linked glycopeptides were isolated from the pooled whole saliva of six age and gender groups by hydrazide chemistry and hydrophilic affinity methods followed by mass spectrometry identification. 24994967 2 17 theme production 245:254 arg1 concentration 264:276 the concentration 260:276 the concentration of whole saliva 260:292 However, the rate of production and the concentration of whole saliva change with age, gender and physiological states of the human body. 24994967 2 17 theme production 245:254 arg1 rate 237:240 the rate 233:240 the rate of production 233:254 However, the rate of production and the concentration of whole saliva change with age, gender and physiological states of the human body. 24994967 0 18 theme human 57:61 arg1 saliva 69:74 human whole saliva 57:74 human whole saliva 57:74 Analysis of age and gender associated N-glycoproteome in human whole saliva. 24994967 3 19 theme clinical 518:525 arg1 utility 527:533 clinical utility 518:533 clinical utility 518:533 Therefore, a thorough understanding of the salivary glycoproteome of healthy individuals of different ages and genders is a prerequisite for saliva to have clinical utility. 24994967 1 20 theme proteome 143:150 arg1 portion 119:125 a large portion 111:125 a large portion of the salivary proteome 111:150 BACKGROUND Glycoproteins comprise a large portion of the salivary proteome and have great potential for biomarker discovery and disease diagnosis. 24994967 4 21 theme affinity 687:694 arg1 methods 696:702 hydrazide chemistry and hydrophilic affinity methods 651:702 hydrazide chemistry and hydrophilic affinity methods followed by mass spectrometry identification 651:747 METHODS Formerly N-linked glycopeptides were isolated from the pooled whole saliva of six age and gender groups by hydrazide chemistry and hydrophilic affinity methods followed by mass spectrometry identification. 24994967 5 22 theme salivary 793:800 arg1 glycoproteins 802:814 salivary glycoproteins 793:814 salivary glycoproteins 793:814 Selected physiochemical characteristics of salivary glycoproteins were analyzed, and the salivary glycoproteomes of different age and gender groups were compared based on their glycoprotein components and gene ontology. 24994967 5 23 theme glycoprotein 927:938 arg1 components 940:949 their glycoprotein components 921:949 their glycoprotein components 921:949 Selected physiochemical characteristics of salivary glycoproteins were analyzed, and the salivary glycoproteomes of different age and gender groups were compared based on their glycoprotein components and gene ontology. 24994967 10 24 theme salivary 1529:1536 arg1 glycoproteins 1538:1550 salivary glycoproteins 1529:1550 salivary glycoproteins 1529:1550 This study reveals the important role of salivary glycoproteins in the maintenance of oral health and homeostasis and the great potential of saliva for biomarker discovery and disease diagnosis. 24994967 6 25 theme healthy 1032:1038 arg1 saliva 1046:1051 healthy human saliva 1032:1051 healthy human saliva 1032:1051 RESULTS AND DISCUSSION Among 85 N-glycoproteins identified in healthy human saliva, the majority were acidic proteins with low molecular weight. 24994967 10 26 theme oral 1574:1577 arg1 health 1579:1584 oral health 1574:1584 oral health 1574:1584 This study reveals the important role of salivary glycoproteins in the maintenance of oral health and homeostasis and the great potential of saliva for biomarker discovery and disease diagnosis. 24994967 3 27 theme glycoproteome 414:426 arg1 prerequisite 486:497 a prerequisite 484:497 a prerequisite for saliva to have clinical utility 484:533 Therefore, a thorough understanding of the salivary glycoproteome of healthy individuals of different ages and genders is a prerequisite for saliva to have clinical utility. 24994967 3 27 theme glycoproteome 414:426 arg1 understanding 384:396 a thorough understanding 373:396 a thorough understanding of the salivary glycoproteome of healthy individuals of different ages and genders 373:479 Therefore, a thorough understanding of the salivary glycoproteome of healthy individuals of different ages and genders is a prerequisite for saliva to have clinical utility. 24994967 5 28 theme Selected 750:757 arg1 characteristics 774:788 Selected physiochemical characteristics 750:788 Selected physiochemical characteristics of salivary glycoproteins 750:814 Selected physiochemical characteristics of salivary glycoproteins were analyzed, and the salivary glycoproteomes of different age and gender groups were compared based on their glycoprotein components and gene ontology. 24994967 4 29 dep METHODS 536:542 arg1 glycopeptides 562:574 Formerly N-linked glycopeptides 544:574 METHODS Formerly N-linked glycopeptides 536:574 METHODS Formerly N-linked glycopeptides were isolated from the pooled whole saliva of six age and gender groups by hydrazide chemistry and hydrophilic affinity methods followed by mass spectrometry identification. 24994967 4 30 gly glycopeptides 562:574 arg2 glycopeptides 562:574 Formerly N-linked glycopeptides 544:574 METHODS Formerly N-linked glycopeptides 536:574 METHODS Formerly N-linked glycopeptides were isolated from the pooled whole saliva of six age and gender groups by hydrazide chemistry and hydrophilic affinity methods followed by mass spectrometry identification. 24994967 0 31 theme whole 63:67 arg1 saliva 69:74 human whole saliva 57:74 human whole saliva 57:74 Analysis of age and gender associated N-glycoproteome in human whole saliva. 24994967 0 32 theme age 12:14 arg1 Analysis 0:7 Analysis 0:7 Analysis of age and gender 0:25 Analysis of age and gender associated N-glycoproteome in human whole saliva. 24994967 6 33 theme low 1093:1095 arg1 weight 1107:1112 low molecular weight 1093:1112 low molecular weight 1093:1112 RESULTS AND DISCUSSION Among 85 N-glycoproteins identified in healthy human saliva, the majority were acidic proteins with low molecular weight. 24994967 3 34 theme healthy 431:437 arg1 individuals 439:449 healthy individuals 431:449 healthy individuals 431:449 Therefore, a thorough understanding of the salivary glycoproteome of healthy individuals of different ages and genders is a prerequisite for saliva to have clinical utility. 24994967 4 35 theme groups 641:646 arg1 saliva 612:617 the pooled whole saliva 595:617 the pooled whole saliva of six age and gender groups 595:646 METHODS Formerly N-linked glycopeptides were isolated from the pooled whole saliva of six age and gender groups by hydrazide chemistry and hydrophilic affinity methods followed by mass spectrometry identification. 24994967 0 36 theme gender 20:25 arg1 Analysis 0:7 Analysis 0:7 Analysis of age and gender 0:25 Analysis of age and gender associated N-glycoproteome in human whole saliva. 24994967 8 37 gly glycoproteins 1192:1204 arg1 functions 1298:1306 functions 1298:1306 functions related to innate immunity against microorganisms and oral cavity protection 1298:1383 Fifteen salivary glycoproteins were identified as potential age- or gender-associated glycoproteins, and many of them have functions related to innate immunity against microorganisms and oral cavity protection. 24994967 8 37 gly glycoproteins 1192:1204 arg1 age- 1235:1238 potential age- 1225:1238 potential age- 1225:1238 Fifteen salivary glycoproteins were identified as potential age- or gender-associated glycoproteins, and many of them have functions related to innate immunity against microorganisms and oral cavity protection. 24994967 8 37 gly glycoproteins 1192:1204 arg1 glycoproteins 1192:1204 Fifteen salivary glycoproteins 1175:1204 Fifteen salivary glycoproteins 1175:1204 Fifteen salivary glycoproteins were identified as potential age- or gender-associated glycoproteins, and many of them have functions related to innate immunity against microorganisms and oral cavity protection. 24994967 8 37 gly glycoproteins 1192:1204 arg1 glycoproteins 1261:1273 gender-associated glycoproteins 1243:1273 gender-associated glycoproteins 1243:1273 Fifteen salivary glycoproteins were identified as potential age- or gender-associated glycoproteins, and many of them have functions related to innate immunity against microorganisms and oral cavity protection. 24994967 2 38 theme physiological 322:334 arg1 states 336:341 physiological states 322:341 physiological states of the human body 322:359 However, the rate of production and the concentration of whole saliva change with age, gender and physiological states of the human body. 24994967 9 39 theme disease 1457:1463 arg1 glycoproteins 1473:1485 disease related glycoproteins 1457:1485 disease related glycoproteins 1457:1485 Moreover, many salivary glycoproteins have been previously reported as disease related glycoproteins. 24994967 9 39 theme disease 1457:1463 arg1 glycoproteins 1410:1422 many salivary glycoproteins 1396:1422 many salivary glycoproteins 1396:1422 Moreover, many salivary glycoproteins have been previously reported as disease related glycoproteins. 24994967 10 40 theme great 1610:1614 arg1 potential 1616:1624 the great potential 1606:1624 the great potential of saliva for biomarker discovery and disease diagnosis 1606:1680 This study reveals the important role of salivary glycoproteins in the maintenance of oral health and homeostasis and the great potential of saliva for biomarker discovery and disease diagnosis. 24994967 3 41 theme ages 464:467 arg1 glycoproteome 414:426 the salivary glycoproteome 401:426 the salivary glycoproteome of healthy individuals of different ages and genders 401:479 Therefore, a thorough understanding of the salivary glycoproteome of healthy individuals of different ages and genders is a prerequisite for saliva to have clinical utility. 24994967 2 42 theme human 350:354 arg1 body 356:359 the human body 346:359 the human body 346:359 However, the rate of production and the concentration of whole saliva change with age, gender and physiological states of the human body. 24994967 4 43 theme gender 634:639 arg1 groups 641:646 six age and gender groups 622:646 groups 641:646 METHODS Formerly N-linked glycopeptides were isolated from the pooled whole saliva of six age and gender groups by hydrazide chemistry and hydrophilic affinity methods followed by mass spectrometry identification. 24994967 8 44 theme salivary 1183:1190 arg1 functions 1298:1306 functions 1298:1306 functions related to innate immunity against microorganisms and oral cavity protection 1298:1383 Fifteen salivary glycoproteins were identified as potential age- or gender-associated glycoproteins, and many of them have functions related to innate immunity against microorganisms and oral cavity protection. 24994967 8 44 theme salivary 1183:1190 arg1 age- 1235:1238 potential age- 1225:1238 potential age- 1225:1238 Fifteen salivary glycoproteins were identified as potential age- or gender-associated glycoproteins, and many of them have functions related to innate immunity against microorganisms and oral cavity protection. 24994967 8 44 theme salivary 1183:1190 arg1 glycoproteins 1192:1204 Fifteen salivary glycoproteins 1175:1204 Fifteen salivary glycoproteins 1175:1204 Fifteen salivary glycoproteins were identified as potential age- or gender-associated glycoproteins, and many of them have functions related to innate immunity against microorganisms and oral cavity protection. 24994967 8 44 theme salivary 1183:1190 arg1 glycoproteins 1261:1273 gender-associated glycoproteins 1243:1273 gender-associated glycoproteins 1243:1273 Fifteen salivary glycoproteins were identified as potential age- or gender-associated glycoproteins, and many of them have functions related to innate immunity against microorganisms and oral cavity protection. 24994967 4 45 link N-linked 553:560 arg1 glycopeptides 562:574 Formerly N-linked glycopeptides 544:574 METHODS Formerly N-linked glycopeptides 536:574 METHODS Formerly N-linked glycopeptides were isolated from the pooled whole saliva of six age and gender groups by hydrazide chemistry and hydrophilic affinity methods followed by mass spectrometry identification. 24994967 10 46 gly glycoproteins 1538:1550 arg1 glycoproteins 1538:1550 salivary glycoproteins 1529:1550 salivary glycoproteins 1529:1550 This study reveals the important role of salivary glycoproteins in the maintenance of oral health and homeostasis and the great potential of saliva for biomarker discovery and disease diagnosis. 24994967 4 47 theme whole 606:610 arg1 saliva 612:617 the pooled whole saliva 595:617 the pooled whole saliva of six age and gender groups 595:646 METHODS Formerly N-linked glycopeptides were isolated from the pooled whole saliva of six age and gender groups by hydrazide chemistry and hydrophilic affinity methods followed by mass spectrometry identification. 24994967 8 48 gly glycoproteins 1261:1273 arg1 functions 1298:1306 functions 1298:1306 functions related to innate immunity against microorganisms and oral cavity protection 1298:1383 Fifteen salivary glycoproteins were identified as potential age- or gender-associated glycoproteins, and many of them have functions related to innate immunity against microorganisms and oral cavity protection. 24994967 8 48 gly glycoproteins 1261:1273 arg1 glycoproteins 1261:1273 gender-associated glycoproteins 1243:1273 gender-associated glycoproteins 1243:1273 Fifteen salivary glycoproteins were identified as potential age- or gender-associated glycoproteins, and many of them have functions related to innate immunity against microorganisms and oral cavity protection. 24994967 8 48 gly glycoproteins 1261:1273 arg1 glycoproteins 1192:1204 Fifteen salivary glycoproteins 1175:1204 Fifteen salivary glycoproteins 1175:1204 Fifteen salivary glycoproteins were identified as potential age- or gender-associated glycoproteins, and many of them have functions related to innate immunity against microorganisms and oral cavity protection. 24994967 2 49 theme whole 281:285 arg1 saliva 287:292 whole saliva 281:292 whole saliva 281:292 However, the rate of production and the concentration of whole saliva change with age, gender and physiological states of the human body. 24994967 10 50 theme disease 1664:1670 arg1 diagnosis 1672:1680 disease diagnosis 1664:1680 disease diagnosis 1664:1680 This study reveals the important role of salivary glycoproteins in the maintenance of oral health and homeostasis and the great potential of saliva for biomarker discovery and disease diagnosis. 24994967 3 51 theme genders 473:479 arg1 glycoproteome 414:426 the salivary glycoproteome 401:426 the salivary glycoproteome of healthy individuals of different ages and genders 401:479 Therefore, a thorough understanding of the salivary glycoproteome of healthy individuals of different ages and genders is a prerequisite for saliva to have clinical utility. 24994967 7 52 theme N-glycoproteins 1139:1153 arg1 numbers 1119:1125 The numbers 1115:1125 The numbers of salivary N-glycoproteins 1115:1153 The numbers of salivary N-glycoproteins increased with age. 24994967 5 53 theme gender 884:889 arg1 groups 891:896 different age and gender groups 866:896 different age and gender groups 866:896 Selected physiochemical characteristics of salivary glycoproteins were analyzed, and the salivary glycoproteomes of different age and gender groups were compared based on their glycoprotein components and gene ontology. 24994967 7 54 gly N-glycoproteins 1139:1153 arg1 N-glycoproteins 1139:1153 salivary N-glycoproteins 1130:1153 salivary N-glycoproteins 1130:1153 The numbers of salivary N-glycoproteins increased with age. 24994967 10 55 theme important 1511:1519 arg1 role 1521:1524 the important role 1507:1524 the important role of salivary glycoproteins in the maintenance of oral health and homeostasis 1507:1600 This study reveals the important role of salivary glycoproteins in the maintenance of oral health and homeostasis and the great potential of saliva for biomarker discovery and disease diagnosis. 24994967 8 56 theme gender-associated 1243:1259 arg1 functions 1298:1306 functions 1298:1306 functions related to innate immunity against microorganisms and oral cavity protection 1298:1383 Fifteen salivary glycoproteins were identified as potential age- or gender-associated glycoproteins, and many of them have functions related to innate immunity against microorganisms and oral cavity protection. 24994967 8 56 theme gender-associated 1243:1259 arg1 glycoproteins 1261:1273 gender-associated glycoproteins 1243:1273 gender-associated glycoproteins 1243:1273 Fifteen salivary glycoproteins were identified as potential age- or gender-associated glycoproteins, and many of them have functions related to innate immunity against microorganisms and oral cavity protection. 24994967 8 56 theme gender-associated 1243:1259 arg1 glycoproteins 1192:1204 Fifteen salivary glycoproteins 1175:1204 Fifteen salivary glycoproteins 1175:1204 Fifteen salivary glycoproteins were identified as potential age- or gender-associated glycoproteins, and many of them have functions related to innate immunity against microorganisms and oral cavity protection. 24994967 6 57 gly 85 N-glycoproteins 999:1016 arg1 85 N-glycoproteins 999:1016 85 N-glycoproteins 999:1016 85 N-glycoproteins identified in healthy human saliva 999:1051 RESULTS AND DISCUSSION Among 85 N-glycoproteins identified in healthy human saliva, the majority were acidic proteins with low molecular weight. 24994967 5 58 theme age 876:878 arg1 groups 891:896 different age and gender groups 866:896 different age and gender groups 866:896 Selected physiochemical characteristics of salivary glycoproteins were analyzed, and the salivary glycoproteomes of different age and gender groups were compared based on their glycoprotein components and gene ontology. 24994967 4 59 theme age 626:628 arg1 saliva 612:617 the pooled whole saliva 595:617 the pooled whole saliva of six age and gender groups 595:646 METHODS Formerly N-linked glycopeptides were isolated from the pooled whole saliva of six age and gender groups by hydrazide chemistry and hydrophilic affinity methods followed by mass spectrometry identification. 24994967 1 60 theme large 113:117 arg1 portion 119:125 a large portion 111:125 a large portion of the salivary proteome 111:150 BACKGROUND Glycoproteins comprise a large portion of the salivary proteome and have great potential for biomarker discovery and disease diagnosis. 24994967 8 61 theme them 1288:1291 arg1 them 1288:1291 them 1288:1291 them 1288:1291 Fifteen salivary glycoproteins were identified as potential age- or gender-associated glycoproteins, and many of them have functions related to innate immunity against microorganisms and oral cavity protection. 24994967 8 61 theme them 1288:1291 arg1 many 1280:1283 many 1280:1283 many 1280:1283 Fifteen salivary glycoproteins were identified as potential age- or gender-associated glycoproteins, and many of them have functions related to innate immunity against microorganisms and oral cavity protection. 24994967 8 62 theme oral 1362:1365 arg1 protection 1374:1383 oral cavity protection 1362:1383 oral cavity protection 1362:1383 Fifteen salivary glycoproteins were identified as potential age- or gender-associated glycoproteins, and many of them have functions related to innate immunity against microorganisms and oral cavity protection. 24994967 5 63 theme gene 955:958 arg1 ontology 960:967 gene ontology 955:967 gene ontology 955:967 Selected physiochemical characteristics of salivary glycoproteins were analyzed, and the salivary glycoproteomes of different age and gender groups were compared based on their glycoprotein components and gene ontology. 24994967 6 64 theme acidic 1072:1077 arg1 proteins 1079:1086 acidic proteins 1072:1086 acidic proteins with low molecular weight 1072:1112 RESULTS AND DISCUSSION Among 85 N-glycoproteins identified in healthy human saliva, the majority were acidic proteins with low molecular weight. 24994967 5 65 theme physiochemical 759:772 arg1 characteristics 774:788 Selected physiochemical characteristics 750:788 Selected physiochemical characteristics of salivary glycoproteins 750:814 Selected physiochemical characteristics of salivary glycoproteins were analyzed, and the salivary glycoproteomes of different age and gender groups were compared based on their glycoprotein components and gene ontology. 24994967 4 66 attach isolated 581:588 arg2 METHODS 536:542 METHODS 536:542 METHODS Formerly N-linked glycopeptides 536:574 METHODS Formerly N-linked glycopeptides were isolated from the pooled whole saliva of six age and gender groups by hydrazide chemistry and hydrophilic affinity methods followed by mass spectrometry identification. 24994967 4 66 attach isolated 581:588 arg1 saliva 612:617 the pooled whole saliva 595:617 the pooled whole saliva of six age and gender groups 595:646 METHODS Formerly N-linked glycopeptides were isolated from the pooled whole saliva of six age and gender groups by hydrazide chemistry and hydrophilic affinity methods followed by mass spectrometry identification. 24994967 1 67 theme salivary 134:141 arg1 proteome 143:150 the salivary proteome 130:150 the salivary proteome 130:150 BACKGROUND Glycoproteins comprise a large portion of the salivary proteome and have great potential for biomarker discovery and disease diagnosis. 24994967 4 68 theme chemistry 661:669 arg1 methods 696:702 hydrazide chemistry and hydrophilic affinity methods 651:702 hydrazide chemistry and hydrophilic affinity methods followed by mass spectrometry identification 651:747 METHODS Formerly N-linked glycopeptides were isolated from the pooled whole saliva of six age and gender groups by hydrazide chemistry and hydrophilic affinity methods followed by mass spectrometry identification. 24994967 10 69 theme glycoproteins 1538:1550 arg1 potential 1616:1624 the great potential 1606:1624 the great potential of saliva for biomarker discovery and disease diagnosis 1606:1680 This study reveals the important role of salivary glycoproteins in the maintenance of oral health and homeostasis and the great potential of saliva for biomarker discovery and disease diagnosis. 24994967 10 69 theme glycoproteins 1538:1550 arg1 role 1521:1524 the important role 1507:1524 the important role of salivary glycoproteins in the maintenance of oral health and homeostasis 1507:1600 This study reveals the important role of salivary glycoproteins in the maintenance of oral health and homeostasis and the great potential of saliva for biomarker discovery and disease diagnosis. 24994967 4 70 theme hydrophilic 675:685 arg1 methods 696:702 hydrazide chemistry and hydrophilic affinity methods 651:702 hydrazide chemistry and hydrophilic affinity methods followed by mass spectrometry identification 651:747 METHODS Formerly N-linked glycopeptides were isolated from the pooled whole saliva of six age and gender groups by hydrazide chemistry and hydrophilic affinity methods followed by mass spectrometry identification. 24994967 6 71 theme human 1040:1044 arg1 saliva 1046:1051 healthy human saliva 1032:1051 healthy human saliva 1032:1051 RESULTS AND DISCUSSION Among 85 N-glycoproteins identified in healthy human saliva, the majority were acidic proteins with low molecular weight. 24994967 9 72 gly glycoproteins 1410:1422 arg1 glycoproteins 1410:1422 many salivary glycoproteins 1396:1422 many salivary glycoproteins 1396:1422 Moreover, many salivary glycoproteins have been previously reported as disease related glycoproteins. 24994967 9 72 gly glycoproteins 1410:1422 arg1 glycoproteins 1473:1485 disease related glycoproteins 1457:1485 disease related glycoproteins 1457:1485 Moreover, many salivary glycoproteins have been previously reported as disease related glycoproteins. 24994967 10 73 from potential 1616:1624 arg1 maintenance 1559:1569 the maintenance 1555:1569 the maintenance of oral health and homeostasis 1555:1600 This study reveals the important role of salivary glycoproteins in the maintenance of oral health and homeostasis and the great potential of saliva for biomarker discovery and disease diagnosis. 24994967 9 74 theme salivary 1401:1408 arg1 glycoproteins 1410:1422 many salivary glycoproteins 1396:1422 many salivary glycoproteins 1396:1422 Moreover, many salivary glycoproteins have been previously reported as disease related glycoproteins. 24994967 9 74 theme salivary 1401:1408 arg1 glycoproteins 1473:1485 disease related glycoproteins 1457:1485 disease related glycoproteins 1457:1485 Moreover, many salivary glycoproteins have been previously reported as disease related glycoproteins. 24994967 1 75 theme BACKGROUND 77:86 arg1 Glycoproteins 88:100 BACKGROUND Glycoproteins 77:100 BACKGROUND Glycoproteins 77:100 BACKGROUND Glycoproteins comprise a large portion of the salivary proteome and have great potential for biomarker discovery and disease diagnosis. 24994967 4 76 theme spectrometry 721:732 arg1 identification 734:747 mass spectrometry identification 716:747 mass spectrometry identification 716:747 METHODS Formerly N-linked glycopeptides were isolated from the pooled whole saliva of six age and gender groups by hydrazide chemistry and hydrophilic affinity methods followed by mass spectrometry identification. 24994967 3 77 theme salivary 405:412 arg1 glycoproteome 414:426 the salivary glycoproteome 401:426 the salivary glycoproteome of healthy individuals of different ages and genders 401:479 Therefore, a thorough understanding of the salivary glycoproteome of healthy individuals of different ages and genders is a prerequisite for saliva to have clinical utility. 24994967 5 78 theme salivary 839:846 arg1 glycoproteomes 848:861 the salivary glycoproteomes 835:861 the salivary glycoproteomes of different age and gender groups 835:896 Selected physiochemical characteristics of salivary glycoproteins were analyzed, and the salivary glycoproteomes of different age and gender groups were compared based on their glycoprotein components and gene ontology. 24994967 6 79 theme molecular 1097:1105 arg1 weight 1107:1112 low molecular weight 1093:1112 low molecular weight 1093:1112 RESULTS AND DISCUSSION Among 85 N-glycoproteins identified in healthy human saliva, the majority were acidic proteins with low molecular weight. 24994967 4 80 theme N-linked 553:560 arg1 glycopeptides 562:574 Formerly N-linked glycopeptides 544:574 METHODS Formerly N-linked glycopeptides 536:574 METHODS Formerly N-linked glycopeptides were isolated from the pooled whole saliva of six age and gender groups by hydrazide chemistry and hydrophilic affinity methods followed by mass spectrometry identification. 24994967 10 81 theme homeostasis 1590:1600 arg1 maintenance 1559:1569 the maintenance 1555:1569 the maintenance of oral health and homeostasis 1555:1600 This study reveals the important role of salivary glycoproteins in the maintenance of oral health and homeostasis and the great potential of saliva for biomarker discovery and disease diagnosis. 24994967 3 82 theme different 454:462 arg1 ages 464:467 different ages 454:467 different ages 454:467 Therefore, a thorough understanding of the salivary glycoproteome of healthy individuals of different ages and genders is a prerequisite for saliva to have clinical utility. 24994967 5 83 theme glycoproteins 802:814 arg1 characteristics 774:788 Selected physiochemical characteristics 750:788 Selected physiochemical characteristics of salivary glycoproteins 750:814 Selected physiochemical characteristics of salivary glycoproteins were analyzed, and the salivary glycoproteomes of different age and gender groups were compared based on their glycoprotein components and gene ontology. 24994967 1 84 theme disease 205:211 arg1 diagnosis 213:221 disease diagnosis 205:221 disease diagnosis 205:221 BACKGROUND Glycoproteins comprise a large portion of the salivary proteome and have great potential for biomarker discovery and disease diagnosis. 24994967 10 85 theme health 1579:1584 arg1 maintenance 1559:1569 the maintenance 1555:1569 the maintenance of oral health and homeostasis 1555:1600 This study reveals the important role of salivary glycoproteins in the maintenance of oral health and homeostasis and the great potential of saliva for biomarker discovery and disease diagnosis. 24994967 9 86 gly glycoproteins 1473:1485 arg1 glycoproteins 1473:1485 disease related glycoproteins 1457:1485 disease related glycoproteins 1457:1485 Moreover, many salivary glycoproteins have been previously reported as disease related glycoproteins. 24994967 9 86 gly glycoproteins 1473:1485 arg1 glycoproteins 1410:1422 many salivary glycoproteins 1396:1422 many salivary glycoproteins 1396:1422 Moreover, many salivary glycoproteins have been previously reported as disease related glycoproteins. 24994967 3 87 theme individuals 439:449 arg1 glycoproteome 414:426 the salivary glycoproteome 401:426 the salivary glycoproteome of healthy individuals of different ages and genders 401:479 Therefore, a thorough understanding of the salivary glycoproteome of healthy individuals of different ages and genders is a prerequisite for saliva to have clinical utility. 24994967 9 88 theme many 1396:1399 arg1 glycoproteins 1410:1422 many salivary glycoproteins 1396:1422 many salivary glycoproteins 1396:1422 Moreover, many salivary glycoproteins have been previously reported as disease related glycoproteins. 24994967 9 88 theme many 1396:1399 arg1 glycoproteins 1473:1485 disease related glycoproteins 1457:1485 disease related glycoproteins 1457:1485 Moreover, many salivary glycoproteins have been previously reported as disease related glycoproteins. 24994967 3 89 theme thorough 375:382 arg1 prerequisite 486:497 a prerequisite 484:497 a prerequisite for saliva to have clinical utility 484:533 Therefore, a thorough understanding of the salivary glycoproteome of healthy individuals of different ages and genders is a prerequisite for saliva to have clinical utility. 24994967 3 89 theme thorough 375:382 arg1 understanding 384:396 a thorough understanding 373:396 a thorough understanding of the salivary glycoproteome of healthy individuals of different ages and genders 373:479 Therefore, a thorough understanding of the salivary glycoproteome of healthy individuals of different ages and genders is a prerequisite for saliva to have clinical utility. 24994967 9 90 theme related 1465:1471 arg1 glycoproteins 1473:1485 disease related glycoproteins 1457:1485 disease related glycoproteins 1457:1485 Moreover, many salivary glycoproteins have been previously reported as disease related glycoproteins. 24994967 9 90 theme related 1465:1471 arg1 glycoproteins 1410:1422 many salivary glycoproteins 1396:1422 many salivary glycoproteins 1396:1422 Moreover, many salivary glycoproteins have been previously reported as disease related glycoproteins. 24994967 6 91 with proteins 1079:1086 arg1 weight 1107:1112 low molecular weight 1093:1112 low molecular weight 1093:1112 RESULTS AND DISCUSSION Among 85 N-glycoproteins identified in healthy human saliva, the majority were acidic proteins with low molecular weight. 24994967 4 92 theme pooled 599:604 arg1 saliva 612:617 the pooled whole saliva 595:617 the pooled whole saliva of six age and gender groups 595:646 METHODS Formerly N-linked glycopeptides were isolated from the pooled whole saliva of six age and gender groups by hydrazide chemistry and hydrophilic affinity methods followed by mass spectrometry identification. 24994967 5 93 gly glycoproteins 802:814 arg1 glycoproteins 802:814 salivary glycoproteins 793:814 salivary glycoproteins 793:814 Selected physiochemical characteristics of salivary glycoproteins were analyzed, and the salivary glycoproteomes of different age and gender groups were compared based on their glycoprotein components and gene ontology. 24994967 10 94 theme biomarker 1640:1648 arg1 discovery 1650:1658 biomarker discovery 1640:1658 biomarker discovery 1640:1658 This study reveals the important role of salivary glycoproteins in the maintenance of oral health and homeostasis and the great potential of saliva for biomarker discovery and disease diagnosis. 29128356 4 0 theme homolog 498:504 arg1 potential 472:480 the protective potential 457:480 the protective potential of a novel ApoD homolog, BmApoD1, in Bombyx mori 457:529 In this study, we investigated the protective potential of a novel ApoD homolog, BmApoD1, in Bombyx mori. 29128356 10 1 from tissues 1384:1390 arg1 up-regulation 1348:1360 the transcriptional up-regulation 1328:1360 the transcriptional up-regulation of BmApoD1 in several tissues upon oxidative insult 1328:1412 These observations, together with the transcriptional up-regulation of BmApoD1 in several tissues upon oxidative insult, identify BmApoD1 as a potent antioxidant. 29128356 7 2 link N-linked 879:886 arg1 glycans 888:894 N-linked glycans 879:894 N-linked glycans of BmApoD1 879:905 In addition, we provided evidence that N-linked glycans of BmApoD1 are essential to BmApoD1 secretion, and three residues, namely, Asp69, Asp104, and Asp196, are the glycosylation sites of BmApoD1. 29128356 8 3 theme oxidant 1124:1130 arg1 treatment 1146:1154 oxidant or starvation treatment 1124:1154 treatment 1146:1154 Furthermore, we showed that BmApoD1 is significantly up-regulated in the larvae after oxidant or starvation treatment. 29128356 9 4 theme recombinant 1161:1171 arg1 protein 1181:1187 The recombinant BmApoD1 protein 1157:1187 The recombinant BmApoD1 protein 1157:1187 The recombinant BmApoD1 protein can protect cells from oxidative stress induced by H2O2 and reduce actinomycin D-induced cell apoptosis. 29128356 4 5 theme protective 461:470 arg1 potential 472:480 the protective potential 457:480 the protective potential of a novel ApoD homolog, BmApoD1, in Bombyx mori 457:529 In this study, we investigated the protective potential of a novel ApoD homolog, BmApoD1, in Bombyx mori. 29128356 9 6 theme BmApoD1 1173:1179 arg1 protein 1181:1187 The recombinant BmApoD1 protein 1157:1187 The recombinant BmApoD1 protein 1157:1187 The recombinant BmApoD1 protein can protect cells from oxidative stress induced by H2O2 and reduce actinomycin D-induced cell apoptosis. 29128356 10 7 theme BmApoD1 1365:1371 arg1 up-regulation 1348:1360 the transcriptional up-regulation 1328:1360 the transcriptional up-regulation of BmApoD1 in several tissues upon oxidative insult 1328:1412 These observations, together with the transcriptional up-regulation of BmApoD1 in several tissues upon oxidative insult, identify BmApoD1 as a potent antioxidant. 29128356 0 8 theme Bombyx 92:97 arg1 mori 99:102 Bombyx mori 92:102 Bombyx mori 92:102 Secreted glycoprotein BmApoD1 plays a critical role in anti-oxidation and anti-apoptosis in Bombyx mori. 29128356 3 9 from functions 377:385 arg1 insects 403:409 lepidopteran insects 390:409 lepidopteran insects 390:409 However, few information on their functions in lepidopteran insects are available. 29128356 6 10 theme recombinant 773:783 arg1 protein 793:799 recombinant BmApoD1 protein 773:799 recombinant BmApoD1 protein 773:799 Tryptophan fluorescence titration demonstrated that recombinant BmApoD1 protein can bind retinoic acid and ergosterol. 29128356 5 11 theme low 612:614 arg1 levels 616:621 low levels 612:621 low levels 612:621 Quantitative PCR analyses demonstrated that BmApoD1 is extensively expressed at low levels during the larval stage but abundantly expressed in the testis during the pupal and adult stages. 29128356 2 12 theme lepidopteran 284:295 arg1 insects 297:303 lepidopteran insects 284:303 lepidopteran insects 284:303 Unlike mammals and Drosophila, lepidopteran insects possess three distinct ApoD homologs. 29128356 7 13 gly glycosylation 1006:1018 arg2 BmApoD1 1029:1035 BmApoD1 1029:1035 BmApoD1 1029:1035 In addition, we provided evidence that N-linked glycans of BmApoD1 are essential to BmApoD1 secretion, and three residues, namely, Asp69, Asp104, and Asp196, are the glycosylation sites of BmApoD1. 29128356 7 13 gly glycosylation 1006:1018 arg1 BmApoD1 1029:1035 BmApoD1 1029:1035 BmApoD1 1029:1035 In addition, we provided evidence that N-linked glycans of BmApoD1 are essential to BmApoD1 secretion, and three residues, namely, Asp69, Asp104, and Asp196, are the glycosylation sites of BmApoD1. 29128356 7 13 gly glycosylation 1006:1018 arg2 residues 953:960 three residues 947:960 three residues 947:960 In addition, we provided evidence that N-linked glycans of BmApoD1 are essential to BmApoD1 secretion, and three residues, namely, Asp69, Asp104, and Asp196, are the glycosylation sites of BmApoD1. 29128356 7 13 gly glycosylation 1006:1018 arg2 sites 1020:1024 the glycosylation sites 1002:1024 the glycosylation sites of BmApoD1 1002:1035 In addition, we provided evidence that N-linked glycans of BmApoD1 are essential to BmApoD1 secretion, and three residues, namely, Asp69, Asp104, and Asp196, are the glycosylation sites of BmApoD1. 29128356 3 14 theme few 352:354 arg1 information 356:366 few information 352:366 few information on their functions in lepidopteran insects 352:409 However, few information on their functions in lepidopteran insects are available. 29128356 7 15 theme N-linked 879:886 arg1 glycans 888:894 N-linked glycans 879:894 N-linked glycans of BmApoD1 879:905 In addition, we provided evidence that N-linked glycans of BmApoD1 are essential to BmApoD1 secretion, and three residues, namely, Asp69, Asp104, and Asp196, are the glycosylation sites of BmApoD1. 29128356 4 16 theme ApoD 493:496 arg1 BmApoD1 507:513 BmApoD1 507:513 BmApoD1 507:513 In this study, we investigated the protective potential of a novel ApoD homolog, BmApoD1, in Bombyx mori. 29128356 4 16 theme ApoD 493:496 arg1 homolog 498:504 a novel ApoD homolog 485:504 a novel ApoD homolog 485:504 In this study, we investigated the protective potential of a novel ApoD homolog, BmApoD1, in Bombyx mori. 29128356 11 17 theme B. mori 1534:1540 arg1 adaptation 1520:1529 metabolic adaptation 1510:1529 metabolic adaptation of B. mori to environmental challenges 1510:1568 Our results demonstrate that BmApoD1 is critical for metabolic adaptation of B. mori to environmental challenges. 29128356 6 18 theme retinoic 810:817 arg1 acid 819:822 retinoic acid 810:822 retinoic acid 810:822 Tryptophan fluorescence titration demonstrated that recombinant BmApoD1 protein can bind retinoic acid and ergosterol. 29128356 9 19 from stress 1222:1227 arg1 cells 1201:1205 cells 1201:1205 cells from oxidative stress induced by H2O2 1201:1243 The recombinant BmApoD1 protein can protect cells from oxidative stress induced by H2O2 and reduce actinomycin D-induced cell apoptosis. 29128356 0 20 theme glycoprotein 9:20 arg1 BmApoD1 22:28 Secreted glycoprotein BmApoD1 0:28 Secreted glycoprotein BmApoD1 0:28 Secreted glycoprotein BmApoD1 plays a critical role in anti-oxidation and anti-apoptosis in Bombyx mori. 29128356 4 21 theme novel 487:491 arg1 BmApoD1 507:513 BmApoD1 507:513 BmApoD1 507:513 In this study, we investigated the protective potential of a novel ApoD homolog, BmApoD1, in Bombyx mori. 29128356 4 21 theme novel 487:491 arg1 homolog 498:504 a novel ApoD homolog 485:504 a novel ApoD homolog 485:504 In this study, we investigated the protective potential of a novel ApoD homolog, BmApoD1, in Bombyx mori. 29128356 5 22 theme larval 634:639 arg1 stage 641:645 the larval stage 630:645 the larval stage 630:645 Quantitative PCR analyses demonstrated that BmApoD1 is extensively expressed at low levels during the larval stage but abundantly expressed in the testis during the pupal and adult stages. 29128356 2 23 theme ApoD 328:331 arg1 homologs 333:340 three distinct ApoD homologs 313:340 three distinct ApoD homologs 313:340 Unlike mammals and Drosophila, lepidopteran insects possess three distinct ApoD homologs. 29128356 7 24 theme BmApoD1 1029:1035 arg1 residues 953:960 three residues 947:960 three residues 947:960 In addition, we provided evidence that N-linked glycans of BmApoD1 are essential to BmApoD1 secretion, and three residues, namely, Asp69, Asp104, and Asp196, are the glycosylation sites of BmApoD1. 29128356 7 24 theme BmApoD1 1029:1035 arg1 sites 1020:1024 the glycosylation sites 1002:1024 the glycosylation sites of BmApoD1 1002:1035 In addition, we provided evidence that N-linked glycans of BmApoD1 are essential to BmApoD1 secretion, and three residues, namely, Asp69, Asp104, and Asp196, are the glycosylation sites of BmApoD1. 29128356 7 24 theme BmApoD1 1029:1035 arg1 BmApoD1 1029:1035 BmApoD1 1029:1035 BmApoD1 1029:1035 In addition, we provided evidence that N-linked glycans of BmApoD1 are essential to BmApoD1 secretion, and three residues, namely, Asp69, Asp104, and Asp196, are the glycosylation sites of BmApoD1. 29128356 0 25 theme Secreted 0:7 arg1 BmApoD1 22:28 Secreted glycoprotein BmApoD1 0:28 Secreted glycoprotein BmApoD1 0:28 Secreted glycoprotein BmApoD1 plays a critical role in anti-oxidation and anti-apoptosis in Bombyx mori. 29128356 2 26 theme distinct 319:326 arg1 homologs 333:340 three distinct ApoD homologs 313:340 three distinct ApoD homologs 313:340 Unlike mammals and Drosophila, lepidopteran insects possess three distinct ApoD homologs. 29128356 3 27 from information 356:366 arg1 functions 377:385 their functions 371:385 their functions in lepidopteran insects 371:409 However, few information on their functions in lepidopteran insects are available. 29128356 4 28 from potential 472:480 arg1 mori 526:529 Bombyx mori 519:529 Bombyx mori 519:529 In this study, we investigated the protective potential of a novel ApoD homolog, BmApoD1, in Bombyx mori. 29128356 9 29 theme oxidative 1212:1220 arg1 stress 1222:1227 oxidative stress 1212:1227 oxidative stress induced by H2O2 1212:1243 The recombinant BmApoD1 protein can protect cells from oxidative stress induced by H2O2 and reduce actinomycin D-induced cell apoptosis. 29128356 1 30 theme neuroprotective 184:198 arg1 functions 216:224 neuroprotective and antioxidant functions 184:224 neuroprotective and antioxidant functions 184:224 Recent studies highlighted that apolipoprotein D (ApoD) and its homologs exert neuroprotective and antioxidant functions in mammals and Drosophila. 29128356 10 31 theme several 1376:1382 arg1 tissues 1384:1390 several tissues 1376:1390 several tissues 1376:1390 These observations, together with the transcriptional up-regulation of BmApoD1 in several tissues upon oxidative insult, identify BmApoD1 as a potent antioxidant. 29128356 1 32 theme Recent 105:110 arg1 studies 112:118 Recent studies 105:118 Recent studies highlighted that apolipoprotein D (ApoD) and its homologs 105:176 Recent studies highlighted that apolipoprotein D (ApoD) and its homologs exert neuroprotective and antioxidant functions in mammals and Drosophila. 29128356 10 33 from BmApoD1 1365:1371 arg1 tissues 1384:1390 several tissues 1376:1390 several tissues 1376:1390 These observations, together with the transcriptional up-regulation of BmApoD1 in several tissues upon oxidative insult, identify BmApoD1 as a potent antioxidant. 29128356 0 34 theme critical 38:45 arg1 role 47:50 a critical role 36:50 a critical role 36:50 Secreted glycoprotein BmApoD1 plays a critical role in anti-oxidation and anti-apoptosis in Bombyx mori. 29128356 5 35 theme adult 707:711 arg1 stages 713:718 the pupal and adult stages 693:718 stages 713:718 Quantitative PCR analyses demonstrated that BmApoD1 is extensively expressed at low levels during the larval stage but abundantly expressed in the testis during the pupal and adult stages. 29128356 0 36 from anti-apoptosis 74:87 arg1 mori 99:102 Bombyx mori 92:102 Bombyx mori 92:102 Secreted glycoprotein BmApoD1 plays a critical role in anti-oxidation and anti-apoptosis in Bombyx mori. 29128356 10 37 from up-regulation 1348:1360 arg1 tissues 1384:1390 several tissues 1376:1390 several tissues 1376:1390 These observations, together with the transcriptional up-regulation of BmApoD1 in several tissues upon oxidative insult, identify BmApoD1 as a potent antioxidant. 29128356 1 38 theme antioxidant 204:214 arg1 functions 216:224 neuroprotective and antioxidant functions 184:224 neuroprotective and antioxidant functions 184:224 Recent studies highlighted that apolipoprotein D (ApoD) and its homologs exert neuroprotective and antioxidant functions in mammals and Drosophila. 29128356 2 39 contain possess 305:311 arg2 homologs 333:340 three distinct ApoD homologs 313:340 three distinct ApoD homologs 313:340 Unlike mammals and Drosophila, lepidopteran insects possess three distinct ApoD homologs. 29128356 2 39 contain possess 305:311 arg1 insects 297:303 lepidopteran insects 284:303 lepidopteran insects 284:303 Unlike mammals and Drosophila, lepidopteran insects possess three distinct ApoD homologs. 29128356 0 40 gly glycoprotein 9:20 arg1 glycoprotein 9:20 Secreted glycoprotein BmApoD1 0:28 Secreted glycoprotein BmApoD1 0:28 Secreted glycoprotein BmApoD1 plays a critical role in anti-oxidation and anti-apoptosis in Bombyx mori. 29128356 5 41 theme Quantitative 532:543 arg1 analyses 549:556 Quantitative PCR analyses 532:556 Quantitative PCR analyses 532:556 Quantitative PCR analyses demonstrated that BmApoD1 is extensively expressed at low levels during the larval stage but abundantly expressed in the testis during the pupal and adult stages. 29128356 10 42 theme potent 1437:1442 arg1 BmApoD1 1424:1430 BmApoD1 1424:1430 BmApoD1 1424:1430 These observations, together with the transcriptional up-regulation of BmApoD1 in several tissues upon oxidative insult, identify BmApoD1 as a potent antioxidant. 29128356 10 42 theme potent 1437:1442 arg1 antioxidant 1444:1454 a potent antioxidant 1435:1454 a potent antioxidant 1435:1454 These observations, together with the transcriptional up-regulation of BmApoD1 in several tissues upon oxidative insult, identify BmApoD1 as a potent antioxidant. 29128356 4 43 theme Bombyx 519:524 arg1 mori 526:529 Bombyx mori 519:529 Bombyx mori 519:529 In this study, we investigated the protective potential of a novel ApoD homolog, BmApoD1, in Bombyx mori. 29128356 0 44 from anti-oxidation 55:68 arg1 mori 99:102 Bombyx mori 92:102 Bombyx mori 92:102 Secreted glycoprotein BmApoD1 plays a critical role in anti-oxidation and anti-apoptosis in Bombyx mori. 29128356 5 45 theme PCR 545:547 arg1 analyses 549:556 Quantitative PCR analyses 532:556 Quantitative PCR analyses 532:556 Quantitative PCR analyses demonstrated that BmApoD1 is extensively expressed at low levels during the larval stage but abundantly expressed in the testis during the pupal and adult stages. 29128356 5 46 theme pupal 697:701 arg1 stages 713:718 the pupal and adult stages 693:718 stages 713:718 Quantitative PCR analyses demonstrated that BmApoD1 is extensively expressed at low levels during the larval stage but abundantly expressed in the testis during the pupal and adult stages. 29128356 10 47 theme transcriptional 1332:1346 arg1 up-regulation 1348:1360 the transcriptional up-regulation 1328:1360 the transcriptional up-regulation of BmApoD1 in several tissues upon oxidative insult 1328:1412 These observations, together with the transcriptional up-regulation of BmApoD1 in several tissues upon oxidative insult, identify BmApoD1 as a potent antioxidant. 29128356 7 48 theme BmApoD1 924:930 arg1 secretion 932:940 BmApoD1 secretion 924:940 BmApoD1 secretion 924:940 In addition, we provided evidence that N-linked glycans of BmApoD1 are essential to BmApoD1 secretion, and three residues, namely, Asp69, Asp104, and Asp196, are the glycosylation sites of BmApoD1. 29128356 7 49 theme glycosylation 1006:1018 arg1 residues 953:960 three residues 947:960 three residues 947:960 In addition, we provided evidence that N-linked glycans of BmApoD1 are essential to BmApoD1 secretion, and three residues, namely, Asp69, Asp104, and Asp196, are the glycosylation sites of BmApoD1. 29128356 7 49 theme glycosylation 1006:1018 arg1 sites 1020:1024 the glycosylation sites 1002:1024 the glycosylation sites of BmApoD1 1002:1035 In addition, we provided evidence that N-linked glycans of BmApoD1 are essential to BmApoD1 secretion, and three residues, namely, Asp69, Asp104, and Asp196, are the glycosylation sites of BmApoD1. 29128356 7 49 theme glycosylation 1006:1018 arg1 BmApoD1 1029:1035 BmApoD1 1029:1035 BmApoD1 1029:1035 In addition, we provided evidence that N-linked glycans of BmApoD1 are essential to BmApoD1 secretion, and three residues, namely, Asp69, Asp104, and Asp196, are the glycosylation sites of BmApoD1. 29128356 11 50 theme environmental 1545:1557 arg1 challenges 1559:1568 environmental challenges 1545:1568 environmental challenges 1545:1568 Our results demonstrate that BmApoD1 is critical for metabolic adaptation of B. mori to environmental challenges. 29128356 11 51 theme metabolic 1510:1518 arg1 adaptation 1520:1529 metabolic adaptation 1510:1529 metabolic adaptation of B. mori to environmental challenges 1510:1568 Our results demonstrate that BmApoD1 is critical for metabolic adaptation of B. mori to environmental challenges. 29128356 9 52 theme actinomycin 1256:1266 arg1 apoptosis 1283:1291 actinomycin D-induced cell apoptosis 1256:1291 actinomycin D-induced cell apoptosis 1256:1291 The recombinant BmApoD1 protein can protect cells from oxidative stress induced by H2O2 and reduce actinomycin D-induced cell apoptosis. 29128356 6 53 theme BmApoD1 785:791 arg1 protein 793:799 recombinant BmApoD1 protein 773:799 recombinant BmApoD1 protein 773:799 Tryptophan fluorescence titration demonstrated that recombinant BmApoD1 protein can bind retinoic acid and ergosterol. 29128356 1 54 theme apolipoprotein 137:150 arg1 ApoD 155:158 ApoD 155:158 ApoD 155:158 Recent studies highlighted that apolipoprotein D (ApoD) and its homologs exert neuroprotective and antioxidant functions in mammals and Drosophila. 29128356 1 54 theme apolipoprotein 137:150 arg1 D 152:152 apolipoprotein D 137:152 apolipoprotein D (ApoD) 137:159 Recent studies highlighted that apolipoprotein D (ApoD) and its homologs exert neuroprotective and antioxidant functions in mammals and Drosophila. 29128356 9 55 theme D-induced 1268:1276 arg1 apoptosis 1283:1291 actinomycin D-induced cell apoptosis 1256:1291 actinomycin D-induced cell apoptosis 1256:1291 The recombinant BmApoD1 protein can protect cells from oxidative stress induced by H2O2 and reduce actinomycin D-induced cell apoptosis. 29128356 6 56 theme fluorescence 732:743 arg1 titration 745:753 Tryptophan fluorescence titration 721:753 Tryptophan fluorescence titration 721:753 Tryptophan fluorescence titration demonstrated that recombinant BmApoD1 protein can bind retinoic acid and ergosterol. 29128356 10 57 theme oxidative 1397:1405 arg1 insult 1407:1412 oxidative insult 1397:1412 oxidative insult 1397:1412 These observations, together with the transcriptional up-regulation of BmApoD1 in several tissues upon oxidative insult, identify BmApoD1 as a potent antioxidant. 29128356 9 58 theme cell 1278:1281 arg1 apoptosis 1283:1291 actinomycin D-induced cell apoptosis 1256:1291 actinomycin D-induced cell apoptosis 1256:1291 The recombinant BmApoD1 protein can protect cells from oxidative stress induced by H2O2 and reduce actinomycin D-induced cell apoptosis. 29128356 6 59 theme Tryptophan 721:730 arg1 titration 745:753 Tryptophan fluorescence titration 721:753 Tryptophan fluorescence titration 721:753 Tryptophan fluorescence titration demonstrated that recombinant BmApoD1 protein can bind retinoic acid and ergosterol. 29128356 3 60 theme lepidopteran 390:401 arg1 insects 403:409 lepidopteran insects 390:409 lepidopteran insects 390:409 However, few information on their functions in lepidopteran insects are available. 29128356 7 61 theme BmApoD1 899:905 arg1 glycans 888:894 N-linked glycans 879:894 N-linked glycans of BmApoD1 879:905 In addition, we provided evidence that N-linked glycans of BmApoD1 are essential to BmApoD1 secretion, and three residues, namely, Asp69, Asp104, and Asp196, are the glycosylation sites of BmApoD1. 29128356 8 62 theme starvation 1135:1144 arg1 treatment 1146:1154 oxidant or starvation treatment 1124:1154 treatment 1146:1154 Furthermore, we showed that BmApoD1 is significantly up-regulated in the larvae after oxidant or starvation treatment. 26650734 0 0 theme Trichuris 79:87 arg1 suis 89:92 Trichuris suis 79:92 Trichuris suis 79:92 Sweet secrets of a therapeutic worm: mass-spectrometric N-glycomic analysis of Trichuris suis. 26650734 3 1 theme chemical 491:498 arg1 treatments 514:523 chemical and enzymatic treatments 491:523 chemical and enzymatic treatments 491:523 Using an off-line LC-MS approach in combination with chemical and enzymatic treatments, we have examined the N-linked oligosaccharides of T. suis. 26650734 6 2 theme glycome 1070:1076 arg1 knowledge 1053:1061 Exact knowledge 1047:1061 Exact knowledge of the glycome of T. suis 1047:1087 Exact knowledge of the glycome of T. suis will facilitate more targeted studies on glycan receptors in the host as well as the engineering of cell lines to produce correctly glycosylated recombinant forms of candidate proteins for future studies on immunomodulation. 26650734 5 3 theme subterminal 997:1007 arg1 N-acetylglucosamine 1026:1044 subterminal α1,3-fucosylated N-acetylglucosamine 997:1044 subterminal α1,3-fucosylated N-acetylglucosamine 997:1044 Such antennal epitopes are similar to ones previously associated with immunomodulation by helminths; here we propose phosphorylcholine modifications predominantly of terminal N-acetylgalactosamine but also of subterminal α1,3-fucosylated N-acetylglucosamine. 26650734 5 4 theme phosphorylcholine 905:921 arg1 modifications 923:935 phosphorylcholine modifications 905:935 phosphorylcholine modifications predominantly of terminal N-acetylgalactosamine but also of subterminal α1,3-fucosylated N-acetylglucosamine 905:1044 Such antennal epitopes are similar to ones previously associated with immunomodulation by helminths; here we propose phosphorylcholine modifications predominantly of terminal N-acetylgalactosamine but also of subterminal α1,3-fucosylated N-acetylglucosamine. 26650734 5 5 theme antennal 793:800 arg1 epitopes 802:809 Such antennal epitopes 788:809 Such antennal epitopes 788:809 Such antennal epitopes are similar to ones previously associated with immunomodulation by helminths; here we propose phosphorylcholine modifications predominantly of terminal N-acetylgalactosamine but also of subterminal α1,3-fucosylated N-acetylglucosamine. 26650734 1 6 theme potential 222:230 arg1 therapy 232:238 a potential therapy 220:238 a potential therapy for inflammatory diseases 220:264 Trichuris suis, a nematode parasite of pigs, has attracted attention as its eggs have been administered to human patients as a potential therapy for inflammatory diseases. 26650734 1 6 theme potential 222:230 arg1 eggs 171:174 its eggs 167:174 its eggs 167:174 Trichuris suis, a nematode parasite of pigs, has attracted attention as its eggs have been administered to human patients as a potential therapy for inflammatory diseases. 26650734 6 7 from receptors 1137:1145 arg1 host 1154:1157 the host 1150:1157 the host 1150:1157 Exact knowledge of the glycome of T. suis will facilitate more targeted studies on glycan receptors in the host as well as the engineering of cell lines to produce correctly glycosylated recombinant forms of candidate proteins for future studies on immunomodulation. 26650734 5 8 theme α1,3-fucosylated 1009:1024 arg1 N-acetylglucosamine 1026:1044 subterminal α1,3-fucosylated N-acetylglucosamine 997:1044 subterminal α1,3-fucosylated N-acetylglucosamine 997:1044 Such antennal epitopes are similar to ones previously associated with immunomodulation by helminths; here we propose phosphorylcholine modifications predominantly of terminal N-acetylgalactosamine but also of subterminal α1,3-fucosylated N-acetylglucosamine. 26650734 3 9 theme N-linked 547:554 arg1 oligosaccharides 556:571 the N-linked oligosaccharides 543:571 the N-linked oligosaccharides of T. suis 543:582 Using an off-line LC-MS approach in combination with chemical and enzymatic treatments, we have examined the N-linked oligosaccharides of T. suis. 26650734 0 10 theme suis 89:92 arg1 analysis 67:74 mass-spectrometric N-glycomic analysis 37:74 Sweet secrets of a therapeutic worm: mass-spectrometric N-glycomic analysis of Trichuris suis. 0:93 Sweet secrets of a therapeutic worm: mass-spectrometric N-glycomic analysis of Trichuris suis. 26650734 6 11 theme recombinant 1234:1244 arg1 forms 1246:1250 correctly glycosylated recombinant forms 1211:1250 correctly glycosylated recombinant forms of candidate proteins 1211:1272 Exact knowledge of the glycome of T. suis will facilitate more targeted studies on glycan receptors in the host as well as the engineering of cell lines to produce correctly glycosylated recombinant forms of candidate proteins for future studies on immunomodulation. 26650734 4 12 theme glycans 693:699 arg1 number 683:688 a number 681:688 a number of glycans 681:699 In addition to the paucimannosidic and oligomannosidic N-glycans typical of many invertebrates, a number of glycans carry N,N'-diacetyllactosamine (LacdiNAc) modified by fucose and/or phosphorylcholine. 26650734 6 13 theme targeted 1110:1117 arg1 studies 1119:1125 more targeted studies 1105:1125 more targeted studies on glycan receptors in the host as well as the engineering of cell lines to produce correctly glycosylated recombinant forms of candidate proteins for future studies on immunomodulation 1105:1311 Exact knowledge of the glycome of T. suis will facilitate more targeted studies on glycan receptors in the host as well as the engineering of cell lines to produce correctly glycosylated recombinant forms of candidate proteins for future studies on immunomodulation. 26650734 6 14 theme glycosylated 1221:1232 arg1 forms 1246:1250 correctly glycosylated recombinant forms 1211:1250 correctly glycosylated recombinant forms of candidate proteins 1211:1272 Exact knowledge of the glycome of T. suis will facilitate more targeted studies on glycan receptors in the host as well as the engineering of cell lines to produce correctly glycosylated recombinant forms of candidate proteins for future studies on immunomodulation. 26650734 5 15 theme terminal 954:961 arg1 N-acetylgalactosamine 963:983 terminal N-acetylgalactosamine 954:983 terminal N-acetylgalactosamine 954:983 Such antennal epitopes are similar to ones previously associated with immunomodulation by helminths; here we propose phosphorylcholine modifications predominantly of terminal N-acetylgalactosamine but also of subterminal α1,3-fucosylated N-acetylglucosamine. 26650734 4 16 theme many 661:664 arg1 invertebrates 666:678 many invertebrates 661:678 many invertebrates 661:678 In addition to the paucimannosidic and oligomannosidic N-glycans typical of many invertebrates, a number of glycans carry N,N'-diacetyllactosamine (LacdiNAc) modified by fucose and/or phosphorylcholine. 26650734 4 17 contain carry 701:705 arg2 N'-diacetyllactosamine 709:730 N'-diacetyllactosamine 709:730 N'-diacetyllactosamine (LacdiNAc) modified by fucose and/or phosphorylcholine 709:785 In addition to the paucimannosidic and oligomannosidic N-glycans typical of many invertebrates, a number of glycans carry N,N'-diacetyllactosamine (LacdiNAc) modified by fucose and/or phosphorylcholine. 26650734 4 17 contain carry 701:705 arg2 N 707:707 N 707:707 N 707:707 In addition to the paucimannosidic and oligomannosidic N-glycans typical of many invertebrates, a number of glycans carry N,N'-diacetyllactosamine (LacdiNAc) modified by fucose and/or phosphorylcholine. 26650734 4 17 contain carry 701:705 arg1 number 683:688 a number 681:688 a number of glycans 681:699 In addition to the paucimannosidic and oligomannosidic N-glycans typical of many invertebrates, a number of glycans carry N,N'-diacetyllactosamine (LacdiNAc) modified by fucose and/or phosphorylcholine. 26650734 6 18 theme lines 1194:1198 arg1 engineering 1174:1184 the engineering 1170:1184 the engineering of cell lines to produce correctly glycosylated recombinant forms of candidate proteins for future studies on immunomodulation 1170:1311 Exact knowledge of the glycome of T. suis will facilitate more targeted studies on glycan receptors in the host as well as the engineering of cell lines to produce correctly glycosylated recombinant forms of candidate proteins for future studies on immunomodulation. 26650734 6 18 theme lines 1194:1198 arg1 receptors 1137:1145 glycan receptors 1130:1145 glycan receptors in the host 1130:1157 Exact knowledge of the glycome of T. suis will facilitate more targeted studies on glycan receptors in the host as well as the engineering of cell lines to produce correctly glycosylated recombinant forms of candidate proteins for future studies on immunomodulation. 26650734 3 19 from approach 462:469 arg1 combination 474:484 combination 474:484 combination with chemical and enzymatic treatments 474:523 Using an off-line LC-MS approach in combination with chemical and enzymatic treatments, we have examined the N-linked oligosaccharides of T. suis. 26650734 6 20 theme suis 1084:1087 arg1 glycome 1070:1076 the glycome 1066:1076 the glycome of T. suis 1066:1087 Exact knowledge of the glycome of T. suis will facilitate more targeted studies on glycan receptors in the host as well as the engineering of cell lines to produce correctly glycosylated recombinant forms of candidate proteins for future studies on immunomodulation. 26650734 3 21 with combination 474:484 arg1 treatments 514:523 chemical and enzymatic treatments 491:523 chemical and enzymatic treatments 491:523 Using an off-line LC-MS approach in combination with chemical and enzymatic treatments, we have examined the N-linked oligosaccharides of T. suis. 26650734 6 22 theme Exact 1047:1051 arg1 knowledge 1053:1061 Exact knowledge 1047:1061 Exact knowledge of the glycome of T. suis 1047:1087 Exact knowledge of the glycome of T. suis will facilitate more targeted studies on glycan receptors in the host as well as the engineering of cell lines to produce correctly glycosylated recombinant forms of candidate proteins for future studies on immunomodulation. 26650734 6 23 theme glycan 1130:1135 arg1 receptors 1137:1145 glycan receptors 1130:1145 glycan receptors in the host 1130:1157 Exact knowledge of the glycome of T. suis will facilitate more targeted studies on glycan receptors in the host as well as the engineering of cell lines to produce correctly glycosylated recombinant forms of candidate proteins for future studies on immunomodulation. 26650734 0 24 theme Sweet 0:4 arg1 secrets 6:12 Sweet secrets 0:12 Sweet secrets of a therapeutic worm: mass-spectrometric N-glycomic analysis of Trichuris suis. 0:93 Sweet secrets of a therapeutic worm: mass-spectrometric N-glycomic analysis of Trichuris suis. 26650734 1 25 theme inflammatory 244:255 arg1 diseases 257:264 inflammatory diseases 244:264 inflammatory diseases 244:264 Trichuris suis, a nematode parasite of pigs, has attracted attention as its eggs have been administered to human patients as a potential therapy for inflammatory diseases. 26650734 6 26 from studies 1119:1125 arg1 engineering 1174:1184 the engineering 1170:1184 the engineering of cell lines to produce correctly glycosylated recombinant forms of candidate proteins for future studies on immunomodulation 1170:1311 Exact knowledge of the glycome of T. suis will facilitate more targeted studies on glycan receptors in the host as well as the engineering of cell lines to produce correctly glycosylated recombinant forms of candidate proteins for future studies on immunomodulation. 26650734 6 26 from studies 1119:1125 arg1 receptors 1137:1145 glycan receptors 1130:1145 glycan receptors in the host 1130:1157 Exact knowledge of the glycome of T. suis will facilitate more targeted studies on glycan receptors in the host as well as the engineering of cell lines to produce correctly glycosylated recombinant forms of candidate proteins for future studies on immunomodulation. 26650734 4 27 theme invertebrates 666:678 arg1 typical 650:656 typical 650:656 typical 650:656 In addition to the paucimannosidic and oligomannosidic N-glycans typical of many invertebrates, a number of glycans carry N,N'-diacetyllactosamine (LacdiNAc) modified by fucose and/or phosphorylcholine. 26650734 6 28 theme candidate 1255:1263 arg1 proteins 1265:1272 candidate proteins 1255:1272 candidate proteins 1255:1272 Exact knowledge of the glycome of T. suis will facilitate more targeted studies on glycan receptors in the host as well as the engineering of cell lines to produce correctly glycosylated recombinant forms of candidate proteins for future studies on immunomodulation. 26650734 6 29 theme future 1278:1283 arg1 studies 1285:1291 future studies 1278:1291 future studies on immunomodulation 1278:1311 Exact knowledge of the glycome of T. suis will facilitate more targeted studies on glycan receptors in the host as well as the engineering of cell lines to produce correctly glycosylated recombinant forms of candidate proteins for future studies on immunomodulation. 26650734 2 30 dep in 336:337 arg1 vitro 339:343 vitro 339:343 vitro 339:343 The immunomodulatory factors remain molecularly uncharacterised, but in vitro studies suggest that glycans on the parasite's excretory/secretory proteins may play a role. 26650734 3 31 theme off-line 447:454 arg1 approach 462:469 an off-line LC-MS approach 444:469 an off-line LC-MS approach in combination with chemical and enzymatic treatments 444:523 Using an off-line LC-MS approach in combination with chemical and enzymatic treatments, we have examined the N-linked oligosaccharides of T. suis. 26650734 2 32 theme immunomodulatory 271:286 arg1 factors 288:294 The immunomodulatory factors 267:294 The immunomodulatory factors 267:294 The immunomodulatory factors remain molecularly uncharacterised, but in vitro studies suggest that glycans on the parasite's excretory/secretory proteins may play a role. 26650734 3 33 theme LC-MS 456:460 arg1 approach 462:469 an off-line LC-MS approach 444:469 an off-line LC-MS approach in combination with chemical and enzymatic treatments 444:523 Using an off-line LC-MS approach in combination with chemical and enzymatic treatments, we have examined the N-linked oligosaccharides of T. suis. 26650734 0 34 theme worm 31:34 arg1 secrets 6:12 Sweet secrets 0:12 Sweet secrets of a therapeutic worm: mass-spectrometric N-glycomic analysis of Trichuris suis. 0:93 Sweet secrets of a therapeutic worm: mass-spectrometric N-glycomic analysis of Trichuris suis. 26650734 4 35 theme typical 650:656 arg1 N-glycans 640:648 the paucimannosidic and oligomannosidic N-glycans 600:648 N-glycans 640:648 In addition to the paucimannosidic and oligomannosidic N-glycans typical of many invertebrates, a number of glycans carry N,N'-diacetyllactosamine (LacdiNAc) modified by fucose and/or phosphorylcholine. 26650734 2 36 theme excretory/secretory 392:410 arg1 proteins 412:419 the parasite's excretory/secretory proteins 377:419 the parasite's excretory/secretory proteins 377:419 The immunomodulatory factors remain molecularly uncharacterised, but in vitro studies suggest that glycans on the parasite's excretory/secretory proteins may play a role. 26650734 0 37 theme therapeutic 19:29 arg1 worm 31:34 a therapeutic worm 17:34 a therapeutic worm 17:34 Sweet secrets of a therapeutic worm: mass-spectrometric N-glycomic analysis of Trichuris suis. 26650734 5 38 theme Such 788:791 arg1 epitopes 802:809 Such antennal epitopes 788:809 Such antennal epitopes 788:809 Such antennal epitopes are similar to ones previously associated with immunomodulation by helminths; here we propose phosphorylcholine modifications predominantly of terminal N-acetylgalactosamine but also of subterminal α1,3-fucosylated N-acetylglucosamine. 26650734 0 39 theme mass-spectrometric 37:54 arg1 analysis 67:74 mass-spectrometric N-glycomic analysis 37:74 Sweet secrets of a therapeutic worm: mass-spectrometric N-glycomic analysis of Trichuris suis. 0:93 Sweet secrets of a therapeutic worm: mass-spectrometric N-glycomic analysis of Trichuris suis. 26650734 0 40 theme N-glycomic 56:65 arg1 analysis 67:74 mass-spectrometric N-glycomic analysis 37:74 Sweet secrets of a therapeutic worm: mass-spectrometric N-glycomic analysis of Trichuris suis. 0:93 Sweet secrets of a therapeutic worm: mass-spectrometric N-glycomic analysis of Trichuris suis. 26650734 2 41 from glycans 366:372 arg1 proteins 412:419 the parasite's excretory/secretory proteins 377:419 the parasite's excretory/secretory proteins 377:419 The immunomodulatory factors remain molecularly uncharacterised, but in vitro studies suggest that glycans on the parasite's excretory/secretory proteins may play a role. 26650734 2 42 theme in 336:337 arg1 studies 345:351 in vitro studies 336:351 in vitro studies 336:351 The immunomodulatory factors remain molecularly uncharacterised, but in vitro studies suggest that glycans on the parasite's excretory/secretory proteins may play a role. 26650734 6 43 gly glycosylated 1221:1232 arg1 proteins 1265:1272 candidate proteins 1255:1272 candidate proteins 1255:1272 Exact knowledge of the glycome of T. suis will facilitate more targeted studies on glycan receptors in the host as well as the engineering of cell lines to produce correctly glycosylated recombinant forms of candidate proteins for future studies on immunomodulation. 26650734 6 43 gly glycosylated 1221:1232 arg1 forms 1246:1250 correctly glycosylated recombinant forms 1211:1250 correctly glycosylated recombinant forms of candidate proteins 1211:1272 Exact knowledge of the glycome of T. suis will facilitate more targeted studies on glycan receptors in the host as well as the engineering of cell lines to produce correctly glycosylated recombinant forms of candidate proteins for future studies on immunomodulation. 26650734 3 44 theme suis 579:582 arg1 oligosaccharides 556:571 the N-linked oligosaccharides 543:571 the N-linked oligosaccharides of T. suis 543:582 Using an off-line LC-MS approach in combination with chemical and enzymatic treatments, we have examined the N-linked oligosaccharides of T. suis. 26650734 6 45 from studies 1285:1291 arg1 immunomodulation 1296:1311 immunomodulation 1296:1311 immunomodulation 1296:1311 Exact knowledge of the glycome of T. suis will facilitate more targeted studies on glycan receptors in the host as well as the engineering of cell lines to produce correctly glycosylated recombinant forms of candidate proteins for future studies on immunomodulation. 26650734 6 46 from engineering 1174:1184 arg1 host 1154:1157 the host 1150:1157 the host 1150:1157 Exact knowledge of the glycome of T. suis will facilitate more targeted studies on glycan receptors in the host as well as the engineering of cell lines to produce correctly glycosylated recombinant forms of candidate proteins for future studies on immunomodulation. 26650734 1 47 theme nematode 113:120 arg1 pigs 134:137 pigs 134:137 pigs 134:137 Trichuris suis, a nematode parasite of pigs, has attracted attention as its eggs have been administered to human patients as a potential therapy for inflammatory diseases. 26650734 1 47 theme nematode 113:120 arg1 parasite 122:129 a nematode parasite 111:129 a nematode parasite of pigs 111:137 Trichuris suis, a nematode parasite of pigs, has attracted attention as its eggs have been administered to human patients as a potential therapy for inflammatory diseases. 26650734 1 47 theme nematode 113:120 arg1 suis 105:108 Trichuris suis 95:108 Trichuris suis 95:108 Trichuris suis, a nematode parasite of pigs, has attracted attention as its eggs have been administered to human patients as a potential therapy for inflammatory diseases. 26650734 1 48 theme Trichuris 95:103 arg1 pigs 134:137 pigs 134:137 pigs 134:137 Trichuris suis, a nematode parasite of pigs, has attracted attention as its eggs have been administered to human patients as a potential therapy for inflammatory diseases. 26650734 1 48 theme Trichuris 95:103 arg1 parasite 122:129 a nematode parasite 111:129 a nematode parasite of pigs 111:137 Trichuris suis, a nematode parasite of pigs, has attracted attention as its eggs have been administered to human patients as a potential therapy for inflammatory diseases. 26650734 1 48 theme Trichuris 95:103 arg1 suis 105:108 Trichuris suis 95:108 Trichuris suis 95:108 Trichuris suis, a nematode parasite of pigs, has attracted attention as its eggs have been administered to human patients as a potential therapy for inflammatory diseases. 26650734 6 49 theme proteins 1265:1272 arg1 forms 1246:1250 correctly glycosylated recombinant forms 1211:1250 correctly glycosylated recombinant forms of candidate proteins 1211:1272 Exact knowledge of the glycome of T. suis will facilitate more targeted studies on glycan receptors in the host as well as the engineering of cell lines to produce correctly glycosylated recombinant forms of candidate proteins for future studies on immunomodulation. 26650734 5 50 gly α1,3-fucosylated 1009:1024 arg1 N-acetylglucosamine 1026:1044 subterminal α1,3-fucosylated N-acetylglucosamine 997:1044 subterminal α1,3-fucosylated N-acetylglucosamine 997:1044 Such antennal epitopes are similar to ones previously associated with immunomodulation by helminths; here we propose phosphorylcholine modifications predominantly of terminal N-acetylgalactosamine but also of subterminal α1,3-fucosylated N-acetylglucosamine. 26650734 1 51 theme human 202:206 arg1 patients 208:215 human patients 202:215 human patients 202:215 Trichuris suis, a nematode parasite of pigs, has attracted attention as its eggs have been administered to human patients as a potential therapy for inflammatory diseases. 26650734 0 52 dep secrets 6:12 arg1 analysis 67:74 mass-spectrometric N-glycomic analysis 37:74 Sweet secrets of a therapeutic worm: mass-spectrometric N-glycomic analysis of Trichuris suis. 0:93 Sweet secrets of a therapeutic worm: mass-spectrometric N-glycomic analysis of Trichuris suis. 26650734 4 53 theme oligomannosidic 624:638 arg1 N-glycans 640:648 the paucimannosidic and oligomannosidic N-glycans 600:648 N-glycans 640:648 In addition to the paucimannosidic and oligomannosidic N-glycans typical of many invertebrates, a number of glycans carry N,N'-diacetyllactosamine (LacdiNAc) modified by fucose and/or phosphorylcholine. 26650734 3 54 theme enzymatic 504:512 arg1 treatments 514:523 chemical and enzymatic treatments 491:523 chemical and enzymatic treatments 491:523 Using an off-line LC-MS approach in combination with chemical and enzymatic treatments, we have examined the N-linked oligosaccharides of T. suis. 26650734 4 55 theme paucimannosidic 604:618 arg1 N-glycans 640:648 the paucimannosidic and oligomannosidic N-glycans 600:648 N-glycans 640:648 In addition to the paucimannosidic and oligomannosidic N-glycans typical of many invertebrates, a number of glycans carry N,N'-diacetyllactosamine (LacdiNAc) modified by fucose and/or phosphorylcholine. 26650734 3 56 link N-linked 547:554 arg1 oligosaccharides 556:571 the N-linked oligosaccharides 543:571 the N-linked oligosaccharides of T. suis 543:582 Using an off-line LC-MS approach in combination with chemical and enzymatic treatments, we have examined the N-linked oligosaccharides of T. suis. 26650734 6 57 theme cell 1189:1192 arg1 lines 1194:1198 cell lines 1189:1198 cell lines 1189:1198 Exact knowledge of the glycome of T. suis will facilitate more targeted studies on glycan receptors in the host as well as the engineering of cell lines to produce correctly glycosylated recombinant forms of candidate proteins for future studies on immunomodulation. 26650734 1 58 theme pigs 134:137 arg1 pigs 134:137 pigs 134:137 pigs 134:137 Trichuris suis, a nematode parasite of pigs, has attracted attention as its eggs have been administered to human patients as a potential therapy for inflammatory diseases. 26650734 1 58 theme pigs 134:137 arg1 parasite 122:129 a nematode parasite 111:129 a nematode parasite of pigs 111:137 Trichuris suis, a nematode parasite of pigs, has attracted attention as its eggs have been administered to human patients as a potential therapy for inflammatory diseases. 26650734 1 58 theme pigs 134:137 arg1 suis 105:108 Trichuris suis 95:108 Trichuris suis 95:108 Trichuris suis, a nematode parasite of pigs, has attracted attention as its eggs have been administered to human patients as a potential therapy for inflammatory diseases. 24962352 1 0 dep BITS 329:332 arg1 Pilani 334:339 Pilani 334:339 Pilani 334:339 In this study, we explored the pharmaceutically underexploited mycobacterial gyrase ATPase (GyrB) domain as a template for a structure-based virtual screening of our in-house (BITS Pilani) compound collection to discover new inhibitors targeting Mycobacterium tuberculosis (M.tb.) 24962352 5 1 dep toxicity 854:861 arg1 limitation 872:881 a major limitation 864:881 a major limitation among the previously reported N-linked aminopiperidine analogues 864:946 Further evaluation of the hERG toxicity (a major limitation among the previously reported N-linked aminopiperidine analogues) indicated these molecules to be completely devoid of cardiotoxicity, a significant achievement within this class. 24962352 1 2 theme collection 351:360 arg1 screening 302:310 a structure-based virtual screening 276:310 a structure-based virtual screening of our in-house (BITS Pilani) compound collection 276:360 In this study, we explored the pharmaceutically underexploited mycobacterial gyrase ATPase (GyrB) domain as a template for a structure-based virtual screening of our in-house (BITS Pilani) compound collection to discover new inhibitors targeting Mycobacterium tuberculosis (M.tb.) 24962352 0 3 theme structure-based 67:81 arg1 design 83:88 structure-based design 67:88 structure-based design 67:88 Gyrase ATPase domain as an antitubercular drug discovery platform: structure-based design and lead optimization of nitrothiazolyl carboxamide analogues. 24962352 2 4 theme enzyme 620:625 arg1 efficacy 627:634 considerable in vitro enzyme efficacy 598:634 considerable in vitro enzyme efficacy 598:634 The hit identified was further customized by using a combination of molecular docking and medicinal chemistry strategies to obtain an optimized analogue displaying considerable in vitro enzyme efficacy and bactericidal properties against the M.tb. 24962352 2 5 theme chemistry 534:542 arg1 strategies 544:553 molecular docking and medicinal chemistry strategies 502:553 molecular docking and medicinal chemistry strategies 502:553 The hit identified was further customized by using a combination of molecular docking and medicinal chemistry strategies to obtain an optimized analogue displaying considerable in vitro enzyme efficacy and bactericidal properties against the M.tb. 24962352 1 6 theme compound 342:349 arg1 collection 351:360 our in-house (BITS Pilani) compound collection 315:360 our in-house (BITS Pilani) compound collection 315:360 In this study, we explored the pharmaceutically underexploited mycobacterial gyrase ATPase (GyrB) domain as a template for a structure-based virtual screening of our in-house (BITS Pilani) compound collection to discover new inhibitors targeting Mycobacterium tuberculosis (M.tb.) 24962352 4 7 theme scanning 789:796 arg1 experiments 810:820 differential scanning fluorimetry experiments 776:820 differential scanning fluorimetry experiments 776:820 The binding affinity of the ligand toward the GyrB domain was reascertained by differential scanning fluorimetry experiments. 24962352 2 8 theme medicinal 524:532 arg1 chemistry 534:542 medicinal chemistry 524:542 medicinal chemistry 524:542 The hit identified was further customized by using a combination of molecular docking and medicinal chemistry strategies to obtain an optimized analogue displaying considerable in vitro enzyme efficacy and bactericidal properties against the M.tb. 24962352 1 9 dep in-house 319:326 arg1 BITS 329:332 BITS Pilani 329:339 BITS Pilani 329:339 In this study, we explored the pharmaceutically underexploited mycobacterial gyrase ATPase (GyrB) domain as a template for a structure-based virtual screening of our in-house (BITS Pilani) compound collection to discover new inhibitors targeting Mycobacterium tuberculosis (M.tb.) 24962352 2 10 theme in 611:612 arg1 efficacy 627:634 considerable in vitro enzyme efficacy 598:634 considerable in vitro enzyme efficacy 598:634 The hit identified was further customized by using a combination of molecular docking and medicinal chemistry strategies to obtain an optimized analogue displaying considerable in vitro enzyme efficacy and bactericidal properties against the M.tb. 24962352 4 11 theme differential 776:787 arg1 experiments 810:820 differential scanning fluorimetry experiments 776:820 differential scanning fluorimetry experiments 776:820 The binding affinity of the ligand toward the GyrB domain was reascertained by differential scanning fluorimetry experiments. 24962352 5 12 theme major 866:870 arg1 limitation 872:881 a major limitation 864:881 a major limitation among the previously reported N-linked aminopiperidine analogues 864:946 Further evaluation of the hERG toxicity (a major limitation among the previously reported N-linked aminopiperidine analogues) indicated these molecules to be completely devoid of cardiotoxicity, a significant achievement within this class. 24962352 5 13 theme significant 1020:1030 arg1 cardiotoxicity 1002:1015 cardiotoxicity 1002:1015 cardiotoxicity 1002:1015 Further evaluation of the hERG toxicity (a major limitation among the previously reported N-linked aminopiperidine analogues) indicated these molecules to be completely devoid of cardiotoxicity, a significant achievement within this class. 24962352 5 13 theme significant 1020:1030 arg1 achievement 1032:1042 a significant achievement 1018:1042 a significant achievement within this class 1018:1060 Further evaluation of the hERG toxicity (a major limitation among the previously reported N-linked aminopiperidine analogues) indicated these molecules to be completely devoid of cardiotoxicity, a significant achievement within this class. 24962352 5 14 theme Further 823:829 arg1 evaluation 831:840 Further evaluation 823:840 Further evaluation of the hERG toxicity (a major limitation among the previously reported N-linked aminopiperidine analogues) 823:947 Further evaluation of the hERG toxicity (a major limitation among the previously reported N-linked aminopiperidine analogues) indicated these molecules to be completely devoid of cardiotoxicity, a significant achievement within this class. 24962352 2 15 theme docking 512:518 arg1 strategies 544:553 molecular docking and medicinal chemistry strategies 502:553 molecular docking and medicinal chemistry strategies 502:553 The hit identified was further customized by using a combination of molecular docking and medicinal chemistry strategies to obtain an optimized analogue displaying considerable in vitro enzyme efficacy and bactericidal properties against the M.tb. 24962352 5 16 link N-linked 913:920 arg1 analogues 938:946 the previously reported N-linked aminopiperidine analogues 889:946 the previously reported N-linked aminopiperidine analogues 889:946 Further evaluation of the hERG toxicity (a major limitation among the previously reported N-linked aminopiperidine analogues) indicated these molecules to be completely devoid of cardiotoxicity, a significant achievement within this class. 24962352 4 17 theme fluorimetry 798:808 arg1 experiments 810:820 differential scanning fluorimetry experiments 776:820 differential scanning fluorimetry experiments 776:820 The binding affinity of the ligand toward the GyrB domain was reascertained by differential scanning fluorimetry experiments. 24962352 0 18 theme ATPase 7:12 arg1 domain 14:19 Gyrase ATPase domain 0:19 Gyrase ATPase domain as an antitubercular drug discovery 0:55 Gyrase ATPase domain as an antitubercular drug discovery platform: structure-based design and lead optimization of nitrothiazolyl carboxamide analogues. 24962352 1 19 theme new 374:376 arg1 inhibitors 378:387 new inhibitors 374:387 new inhibitors targeting Mycobacterium tuberculosis 374:424 In this study, we explored the pharmaceutically underexploited mycobacterial gyrase ATPase (GyrB) domain as a template for a structure-based virtual screening of our in-house (BITS Pilani) compound collection to discover new inhibitors targeting Mycobacterium tuberculosis (M.tb.) 24962352 2 20 theme bactericidal 640:651 arg1 properties 653:662 bactericidal properties 640:662 bactericidal properties 640:662 The hit identified was further customized by using a combination of molecular docking and medicinal chemistry strategies to obtain an optimized analogue displaying considerable in vitro enzyme efficacy and bactericidal properties against the M.tb. 24962352 5 21 theme reported 904:911 arg1 analogues 938:946 the previously reported N-linked aminopiperidine analogues 889:946 the previously reported N-linked aminopiperidine analogues 889:946 Further evaluation of the hERG toxicity (a major limitation among the previously reported N-linked aminopiperidine analogues) indicated these molecules to be completely devoid of cardiotoxicity, a significant achievement within this class. 24962352 0 22 theme Gyrase 0:5 arg1 domain 14:19 Gyrase ATPase domain 0:19 Gyrase ATPase domain as an antitubercular drug discovery 0:55 Gyrase ATPase domain as an antitubercular drug discovery platform: structure-based design and lead optimization of nitrothiazolyl carboxamide analogues. 24962352 5 23 theme hERG 849:852 arg1 toxicity 854:861 the hERG toxicity 845:861 the hERG toxicity (a major limitation among the previously reported N-linked aminopiperidine analogues) 845:947 Further evaluation of the hERG toxicity (a major limitation among the previously reported N-linked aminopiperidine analogues) indicated these molecules to be completely devoid of cardiotoxicity, a significant achievement within this class. 24962352 5 24 theme N-linked 913:920 arg1 analogues 938:946 the previously reported N-linked aminopiperidine analogues 889:946 the previously reported N-linked aminopiperidine analogues 889:946 Further evaluation of the hERG toxicity (a major limitation among the previously reported N-linked aminopiperidine analogues) indicated these molecules to be completely devoid of cardiotoxicity, a significant achievement within this class. 24962352 5 25 theme toxicity 854:861 arg1 evaluation 831:840 Further evaluation 823:840 Further evaluation of the hERG toxicity (a major limitation among the previously reported N-linked aminopiperidine analogues) 823:947 Further evaluation of the hERG toxicity (a major limitation among the previously reported N-linked aminopiperidine analogues) indicated these molecules to be completely devoid of cardiotoxicity, a significant achievement within this class. 24962352 1 26 theme structure-based 278:292 arg1 screening 302:310 a structure-based virtual screening 276:310 a structure-based virtual screening of our in-house (BITS Pilani) compound collection 276:360 In this study, we explored the pharmaceutically underexploited mycobacterial gyrase ATPase (GyrB) domain as a template for a structure-based virtual screening of our in-house (BITS Pilani) compound collection to discover new inhibitors targeting Mycobacterium tuberculosis (M.tb.) 24962352 0 27 theme carboxamide 130:140 arg1 analogues 142:150 nitrothiazolyl carboxamide analogues 115:150 nitrothiazolyl carboxamide analogues 115:150 Gyrase ATPase domain as an antitubercular drug discovery platform: structure-based design and lead optimization of nitrothiazolyl carboxamide analogues. 24962352 1 28 theme underexploited 201:214 arg1 domain 251:256 the pharmaceutically underexploited mycobacterial gyrase ATPase (GyrB) domain 180:256 the pharmaceutically underexploited mycobacterial gyrase ATPase (GyrB) domain 180:256 In this study, we explored the pharmaceutically underexploited mycobacterial gyrase ATPase (GyrB) domain as a template for a structure-based virtual screening of our in-house (BITS Pilani) compound collection to discover new inhibitors targeting Mycobacterium tuberculosis (M.tb.) 24962352 1 28 theme underexploited 201:214 arg1 template 263:270 a template 261:270 a template for a structure-based virtual screening of our in-house (BITS Pilani) compound collection 261:360 In this study, we explored the pharmaceutically underexploited mycobacterial gyrase ATPase (GyrB) domain as a template for a structure-based virtual screening of our in-house (BITS Pilani) compound collection to discover new inhibitors targeting Mycobacterium tuberculosis (M.tb.) 24962352 1 29 theme virtual 294:300 arg1 screening 302:310 a structure-based virtual screening 276:310 a structure-based virtual screening of our in-house (BITS Pilani) compound collection 276:360 In this study, we explored the pharmaceutically underexploited mycobacterial gyrase ATPase (GyrB) domain as a template for a structure-based virtual screening of our in-house (BITS Pilani) compound collection to discover new inhibitors targeting Mycobacterium tuberculosis (M.tb.) 24962352 0 30 theme nitrothiazolyl 115:128 arg1 analogues 142:150 nitrothiazolyl carboxamide analogues 115:150 nitrothiazolyl carboxamide analogues 115:150 Gyrase ATPase domain as an antitubercular drug discovery platform: structure-based design and lead optimization of nitrothiazolyl carboxamide analogues. 24962352 5 31 theme cardiotoxicity 1002:1015 arg1 devoid 992:997 devoid 992:997 devoid 992:997 Further evaluation of the hERG toxicity (a major limitation among the previously reported N-linked aminopiperidine analogues) indicated these molecules to be completely devoid of cardiotoxicity, a significant achievement within this class. 24962352 1 32 theme mycobacterial 216:228 arg1 domain 251:256 the pharmaceutically underexploited mycobacterial gyrase ATPase (GyrB) domain 180:256 the pharmaceutically underexploited mycobacterial gyrase ATPase (GyrB) domain 180:256 In this study, we explored the pharmaceutically underexploited mycobacterial gyrase ATPase (GyrB) domain as a template for a structure-based virtual screening of our in-house (BITS Pilani) compound collection to discover new inhibitors targeting Mycobacterium tuberculosis (M.tb.) 24962352 1 32 theme mycobacterial 216:228 arg1 template 263:270 a template 261:270 a template for a structure-based virtual screening of our in-house (BITS Pilani) compound collection 261:360 In this study, we explored the pharmaceutically underexploited mycobacterial gyrase ATPase (GyrB) domain as a template for a structure-based virtual screening of our in-house (BITS Pilani) compound collection to discover new inhibitors targeting Mycobacterium tuberculosis (M.tb.) 24962352 0 33 theme antitubercular 27:40 arg1 discovery 47:55 an antitubercular drug discovery 24:55 an antitubercular drug discovery 24:55 Gyrase ATPase domain as an antitubercular drug discovery platform: structure-based design and lead optimization of nitrothiazolyl carboxamide analogues. 24962352 1 34 theme gyrase 230:235 arg1 domain 251:256 the pharmaceutically underexploited mycobacterial gyrase ATPase (GyrB) domain 180:256 the pharmaceutically underexploited mycobacterial gyrase ATPase (GyrB) domain 180:256 In this study, we explored the pharmaceutically underexploited mycobacterial gyrase ATPase (GyrB) domain as a template for a structure-based virtual screening of our in-house (BITS Pilani) compound collection to discover new inhibitors targeting Mycobacterium tuberculosis (M.tb.) 24962352 1 34 theme gyrase 230:235 arg1 template 263:270 a template 261:270 a template for a structure-based virtual screening of our in-house (BITS Pilani) compound collection 261:360 In this study, we explored the pharmaceutically underexploited mycobacterial gyrase ATPase (GyrB) domain as a template for a structure-based virtual screening of our in-house (BITS Pilani) compound collection to discover new inhibitors targeting Mycobacterium tuberculosis (M.tb.) 24962352 2 35 dep in 611:612 arg1 vitro 614:618 vitro 614:618 vitro 614:618 The hit identified was further customized by using a combination of molecular docking and medicinal chemistry strategies to obtain an optimized analogue displaying considerable in vitro enzyme efficacy and bactericidal properties against the M.tb. 24962352 1 36 dep discover 365:372 arg1 M.tb 427:430 M.tb 427:430 M.tb 427:430 In this study, we explored the pharmaceutically underexploited mycobacterial gyrase ATPase (GyrB) domain as a template for a structure-based virtual screening of our in-house (BITS Pilani) compound collection to discover new inhibitors targeting Mycobacterium tuberculosis (M.tb.) 24962352 0 37 theme analogues 142:150 arg1 optimization 99:110 optimization 99:110 optimization of nitrothiazolyl carboxamide analogues 99:150 Gyrase ATPase domain as an antitubercular drug discovery platform: structure-based design and lead optimization of nitrothiazolyl carboxamide analogues. 24962352 2 38 theme strategies 544:553 arg1 combination 487:497 a combination 485:497 a combination of molecular docking and medicinal chemistry strategies 485:553 The hit identified was further customized by using a combination of molecular docking and medicinal chemistry strategies to obtain an optimized analogue displaying considerable in vitro enzyme efficacy and bactericidal properties against the M.tb. 24962352 1 39 theme ATPase 237:242 arg1 domain 251:256 the pharmaceutically underexploited mycobacterial gyrase ATPase (GyrB) domain 180:256 the pharmaceutically underexploited mycobacterial gyrase ATPase (GyrB) domain 180:256 In this study, we explored the pharmaceutically underexploited mycobacterial gyrase ATPase (GyrB) domain as a template for a structure-based virtual screening of our in-house (BITS Pilani) compound collection to discover new inhibitors targeting Mycobacterium tuberculosis (M.tb.) 24962352 1 39 theme ATPase 237:242 arg1 template 263:270 a template 261:270 a template for a structure-based virtual screening of our in-house (BITS Pilani) compound collection 261:360 In this study, we explored the pharmaceutically underexploited mycobacterial gyrase ATPase (GyrB) domain as a template for a structure-based virtual screening of our in-house (BITS Pilani) compound collection to discover new inhibitors targeting Mycobacterium tuberculosis (M.tb.) 24962352 2 40 theme considerable 598:609 arg1 efficacy 627:634 considerable in vitro enzyme efficacy 598:634 considerable in vitro enzyme efficacy 598:634 The hit identified was further customized by using a combination of molecular docking and medicinal chemistry strategies to obtain an optimized analogue displaying considerable in vitro enzyme efficacy and bactericidal properties against the M.tb. 24962352 0 41 theme drug 42:45 arg1 discovery 47:55 an antitubercular drug discovery 24:55 an antitubercular drug discovery 24:55 Gyrase ATPase domain as an antitubercular drug discovery platform: structure-based design and lead optimization of nitrothiazolyl carboxamide analogues. 24962352 1 42 theme in-house 319:326 arg1 collection 351:360 our in-house (BITS Pilani) compound collection 315:360 our in-house (BITS Pilani) compound collection 315:360 In this study, we explored the pharmaceutically underexploited mycobacterial gyrase ATPase (GyrB) domain as a template for a structure-based virtual screening of our in-house (BITS Pilani) compound collection to discover new inhibitors targeting Mycobacterium tuberculosis (M.tb.) 24962352 4 43 theme ligand 725:730 arg1 affinity 709:716 The binding affinity 697:716 The binding affinity of the ligand toward the GyrB domain 697:753 The binding affinity of the ligand toward the GyrB domain was reascertained by differential scanning fluorimetry experiments. 24962352 4 44 theme GyrB 743:746 arg1 domain 748:753 the GyrB domain 739:753 the GyrB domain 739:753 The binding affinity of the ligand toward the GyrB domain was reascertained by differential scanning fluorimetry experiments. 24962352 2 45 theme optimized 568:576 arg1 analogue 578:585 an optimized analogue 565:585 an optimized analogue displaying considerable in vitro enzyme efficacy and bactericidal properties against the M.tb 565:679 The hit identified was further customized by using a combination of molecular docking and medicinal chemistry strategies to obtain an optimized analogue displaying considerable in vitro enzyme efficacy and bactericidal properties against the M.tb. 24962352 3 46 theme Rv 686:687 arg1 strain 689:694 Rv strain 686:694 Rv strain 686:694 H37 Rv strain. 24962352 1 47 theme GyrB 245:248 arg1 domain 251:256 the pharmaceutically underexploited mycobacterial gyrase ATPase (GyrB) domain 180:256 the pharmaceutically underexploited mycobacterial gyrase ATPase (GyrB) domain 180:256 In this study, we explored the pharmaceutically underexploited mycobacterial gyrase ATPase (GyrB) domain as a template for a structure-based virtual screening of our in-house (BITS Pilani) compound collection to discover new inhibitors targeting Mycobacterium tuberculosis (M.tb.) 24962352 1 47 theme GyrB 245:248 arg1 template 263:270 a template 261:270 a template for a structure-based virtual screening of our in-house (BITS Pilani) compound collection 261:360 In this study, we explored the pharmaceutically underexploited mycobacterial gyrase ATPase (GyrB) domain as a template for a structure-based virtual screening of our in-house (BITS Pilani) compound collection to discover new inhibitors targeting Mycobacterium tuberculosis (M.tb.) 24962352 2 48 theme molecular 502:510 arg1 docking 512:518 molecular docking 502:518 molecular docking 502:518 The hit identified was further customized by using a combination of molecular docking and medicinal chemistry strategies to obtain an optimized analogue displaying considerable in vitro enzyme efficacy and bactericidal properties against the M.tb. 24962352 5 49 theme aminopiperidine 922:936 arg1 analogues 938:946 the previously reported N-linked aminopiperidine analogues 889:946 the previously reported N-linked aminopiperidine analogues 889:946 Further evaluation of the hERG toxicity (a major limitation among the previously reported N-linked aminopiperidine analogues) indicated these molecules to be completely devoid of cardiotoxicity, a significant achievement within this class. 24962352 4 50 theme binding 701:707 arg1 affinity 709:716 The binding affinity 697:716 The binding affinity of the ligand toward the GyrB domain 697:753 The binding affinity of the ligand toward the GyrB domain was reascertained by differential scanning fluorimetry experiments. 26823725 5 0 theme trophoblast 803:813 arg1 proliferation 815:827 trophoblast proliferation 803:827 trophoblast proliferation 803:827 In this study, we demonstrated that OPN is constitutively expressed in highly invasive phenotype of human choriocarcinoma cell lines of JAR and JEG-3 cells, and OPN could promote trophoblast proliferation and invasion, partly through promoting MMP-9 secretion. 26823725 0 1 from invasion 24:31 arg1 cells 56:60 human trophoblastic cells 36:60 human trophoblastic cells 36:60 Osteopontin facilitates invasion in human trophoblastic cells via promoting matrix metalloproteinase-9 in vitro. 26823725 1 2 theme proper 174:179 arg1 proliferation 193:205 proper trophoblast proliferation 174:205 proper trophoblast proliferation 174:205 Successful implantation of embryo and placentation depend on proper trophoblast proliferation and differentiated into specialized invasive trophoblast. 26823725 7 3 theme OPN 1083:1085 arg1 defects 1098:1104 OPN expression defects 1083:1104 OPN expression defects 1083:1104 Our data showed that the expression of OPN in trophoblast may participate in placentation, OPN expression defects may be involved in gestational trophoblastic diseases. 26823725 6 4 theme JAR 966:968 arg1 lines 985:989 JAR and JEG-3 cell lines 966:989 lines 985:989 Inhibition of OPN will compromise the abilities of proliferation and invasion in JAR and JEG-3 cell lines. 26823725 3 5 gly glycoprotein 460:471 arg1 glycoprotein 460:471 the small integrin-binding ligand N-linked glycoprotein family 417:478 the small integrin-binding ligand N-linked glycoprotein family 417:478 Osteopontin (OPN) is a member of the small integrin-binding ligand N-linked glycoprotein family and participates in cell adhesion and invasion. 26823725 1 6 theme trophoblast 181:191 arg1 proliferation 193:205 proper trophoblast proliferation 174:205 proper trophoblast proliferation 174:205 Successful implantation of embryo and placentation depend on proper trophoblast proliferation and differentiated into specialized invasive trophoblast. 26823725 5 7 theme cells 774:778 arg1 lines 751:755 human choriocarcinoma cell lines 724:755 human choriocarcinoma cell lines of JAR and JEG-3 cells 724:778 In this study, we demonstrated that OPN is constitutively expressed in highly invasive phenotype of human choriocarcinoma cell lines of JAR and JEG-3 cells, and OPN could promote trophoblast proliferation and invasion, partly through promoting MMP-9 secretion. 26823725 6 8 theme invasion 954:961 arg1 abilities 923:931 the abilities 919:931 the abilities of proliferation and invasion in JAR and JEG-3 cell lines 919:989 Inhibition of OPN will compromise the abilities of proliferation and invasion in JAR and JEG-3 cell lines. 26823725 7 9 theme trophoblastic 1137:1149 arg1 diseases 1151:1158 gestational trophoblastic diseases 1125:1158 gestational trophoblastic diseases 1125:1158 Our data showed that the expression of OPN in trophoblast may participate in placentation, OPN expression defects may be involved in gestational trophoblastic diseases. 26823725 7 10 from expression 1017:1026 arg1 trophoblast 1038:1048 trophoblast 1038:1048 trophoblast 1038:1048 Our data showed that the expression of OPN in trophoblast may participate in placentation, OPN expression defects may be involved in gestational trophoblastic diseases. 26823725 6 11 theme proliferation 936:948 arg1 abilities 923:931 the abilities 919:931 the abilities of proliferation and invasion in JAR and JEG-3 cell lines 919:989 Inhibition of OPN will compromise the abilities of proliferation and invasion in JAR and JEG-3 cell lines. 26823725 0 12 theme trophoblastic 42:54 arg1 cells 56:60 human trophoblastic cells 36:60 human trophoblastic cells 36:60 Osteopontin facilitates invasion in human trophoblastic cells via promoting matrix metalloproteinase-9 in vitro. 26823725 3 13 theme cell 500:503 arg1 adhesion 505:512 cell adhesion 500:512 cell adhesion 500:512 Osteopontin (OPN) is a member of the small integrin-binding ligand N-linked glycoprotein family and participates in cell adhesion and invasion. 26823725 3 14 theme small 421:425 arg1 family 473:478 the small integrin-binding ligand N-linked glycoprotein family 417:478 the small integrin-binding ligand N-linked glycoprotein family 417:478 Osteopontin (OPN) is a member of the small integrin-binding ligand N-linked glycoprotein family and participates in cell adhesion and invasion. 26823725 7 15 theme expression 1087:1096 arg1 defects 1098:1104 OPN expression defects 1083:1104 OPN expression defects 1083:1104 Our data showed that the expression of OPN in trophoblast may participate in placentation, OPN expression defects may be involved in gestational trophoblastic diseases. 26823725 3 16 theme integrin-binding 427:442 arg1 family 473:478 the small integrin-binding ligand N-linked glycoprotein family 417:478 the small integrin-binding ligand N-linked glycoprotein family 417:478 Osteopontin (OPN) is a member of the small integrin-binding ligand N-linked glycoprotein family and participates in cell adhesion and invasion. 26823725 4 17 theme human 608:612 arg1 placenta 614:621 human placenta 608:621 human placenta 608:621 It has been identified that OPN is highly expressed in invasive trophoblasts in human placenta. 26823725 7 18 theme gestational 1125:1135 arg1 diseases 1151:1158 gestational trophoblastic diseases 1125:1158 gestational trophoblastic diseases 1125:1158 Our data showed that the expression of OPN in trophoblast may participate in placentation, OPN expression defects may be involved in gestational trophoblastic diseases. 26823725 5 19 theme invasive 702:709 arg1 phenotype 711:719 highly invasive phenotype 695:719 highly invasive phenotype of human choriocarcinoma cell lines of JAR and JEG-3 cells 695:778 In this study, we demonstrated that OPN is constitutively expressed in highly invasive phenotype of human choriocarcinoma cell lines of JAR and JEG-3 cells, and OPN could promote trophoblast proliferation and invasion, partly through promoting MMP-9 secretion. 26823725 5 20 theme MMP-9 868:872 arg1 secretion 874:882 MMP-9 secretion 868:882 MMP-9 secretion 868:882 In this study, we demonstrated that OPN is constitutively expressed in highly invasive phenotype of human choriocarcinoma cell lines of JAR and JEG-3 cells, and OPN could promote trophoblast proliferation and invasion, partly through promoting MMP-9 secretion. 26823725 1 21 theme Successful 113:122 arg1 implantation 124:135 Successful implantation 113:135 Successful implantation of embryo and placentation 113:162 Successful implantation of embryo and placentation depend on proper trophoblast proliferation and differentiated into specialized invasive trophoblast. 26823725 1 22 theme specialized 231:241 arg1 trophoblast 252:262 specialized invasive trophoblast 231:262 specialized invasive trophoblast 231:262 Successful implantation of embryo and placentation depend on proper trophoblast proliferation and differentiated into specialized invasive trophoblast. 26823725 5 23 theme JAR 760:762 arg1 cells 774:778 JAR and JEG-3 cells 760:778 cells 774:778 In this study, we demonstrated that OPN is constitutively expressed in highly invasive phenotype of human choriocarcinoma cell lines of JAR and JEG-3 cells, and OPN could promote trophoblast proliferation and invasion, partly through promoting MMP-9 secretion. 26823725 1 24 theme invasive 243:250 arg1 trophoblast 252:262 specialized invasive trophoblast 231:262 specialized invasive trophoblast 231:262 Successful implantation of embryo and placentation depend on proper trophoblast proliferation and differentiated into specialized invasive trophoblast. 26823725 3 25 theme glycoprotein 460:471 arg1 family 473:478 the small integrin-binding ligand N-linked glycoprotein family 417:478 the small integrin-binding ligand N-linked glycoprotein family 417:478 Osteopontin (OPN) is a member of the small integrin-binding ligand N-linked glycoprotein family and participates in cell adhesion and invasion. 26823725 2 26 dep trophoblast 337:347 arg1 proliferation 349:361 proliferation 349:361 proliferation 349:361 However, little is known about the regulatory factors and mechanisms in trophoblast proliferation and differentiation. 26823725 2 26 dep trophoblast 337:347 arg1 differentiation 367:381 differentiation 367:381 differentiation 367:381 However, little is known about the regulatory factors and mechanisms in trophoblast proliferation and differentiation. 26823725 5 27 theme JEG-3 768:772 arg1 cells 774:778 JAR and JEG-3 cells 760:778 cells 774:778 In this study, we demonstrated that OPN is constitutively expressed in highly invasive phenotype of human choriocarcinoma cell lines of JAR and JEG-3 cells, and OPN could promote trophoblast proliferation and invasion, partly through promoting MMP-9 secretion. 26823725 0 28 theme human 36:40 arg1 cells 56:60 human trophoblastic cells 36:60 human trophoblastic cells 36:60 Osteopontin facilitates invasion in human trophoblastic cells via promoting matrix metalloproteinase-9 in vitro. 26823725 3 29 theme family 473:478 arg1 Osteopontin 384:394 Osteopontin 384:394 Osteopontin (OPN) 384:400 Osteopontin (OPN) is a member of the small integrin-binding ligand N-linked glycoprotein family and participates in cell adhesion and invasion. 26823725 3 29 theme family 473:478 arg1 member 407:412 a member 405:412 a member of the small integrin-binding ligand N-linked glycoprotein family 405:478 Osteopontin (OPN) is a member of the small integrin-binding ligand N-linked glycoprotein family and participates in cell adhesion and invasion. 26823725 3 30 link N-linked 451:458 arg1 family 473:478 the small integrin-binding ligand N-linked glycoprotein family 417:478 the small integrin-binding ligand N-linked glycoprotein family 417:478 Osteopontin (OPN) is a member of the small integrin-binding ligand N-linked glycoprotein family and participates in cell adhesion and invasion. 26823725 6 31 theme cell 980:983 arg1 lines 985:989 JAR and JEG-3 cell lines 966:989 lines 985:989 Inhibition of OPN will compromise the abilities of proliferation and invasion in JAR and JEG-3 cell lines. 26823725 3 32 theme ligand 444:449 arg1 family 473:478 the small integrin-binding ligand N-linked glycoprotein family 417:478 the small integrin-binding ligand N-linked glycoprotein family 417:478 Osteopontin (OPN) is a member of the small integrin-binding ligand N-linked glycoprotein family and participates in cell adhesion and invasion. 26823725 6 33 from abilities 923:931 arg1 lines 985:989 JAR and JEG-3 cell lines 966:989 lines 985:989 Inhibition of OPN will compromise the abilities of proliferation and invasion in JAR and JEG-3 cell lines. 26823725 5 34 theme human 724:728 arg1 lines 751:755 human choriocarcinoma cell lines 724:755 human choriocarcinoma cell lines of JAR and JEG-3 cells 724:778 In this study, we demonstrated that OPN is constitutively expressed in highly invasive phenotype of human choriocarcinoma cell lines of JAR and JEG-3 cells, and OPN could promote trophoblast proliferation and invasion, partly through promoting MMP-9 secretion. 26823725 3 35 theme N-linked 451:458 arg1 family 473:478 the small integrin-binding ligand N-linked glycoprotein family 417:478 the small integrin-binding ligand N-linked glycoprotein family 417:478 Osteopontin (OPN) is a member of the small integrin-binding ligand N-linked glycoprotein family and participates in cell adhesion and invasion. 26823725 5 36 theme choriocarcinoma 730:744 arg1 lines 751:755 human choriocarcinoma cell lines 724:755 human choriocarcinoma cell lines of JAR and JEG-3 cells 724:778 In this study, we demonstrated that OPN is constitutively expressed in highly invasive phenotype of human choriocarcinoma cell lines of JAR and JEG-3 cells, and OPN could promote trophoblast proliferation and invasion, partly through promoting MMP-9 secretion. 26823725 6 37 theme OPN 899:901 arg1 Inhibition 885:894 Inhibition 885:894 Inhibition of OPN 885:901 Inhibition of OPN will compromise the abilities of proliferation and invasion in JAR and JEG-3 cell lines. 26823725 1 38 theme embryo 140:145 arg1 implantation 124:135 Successful implantation 113:135 Successful implantation of embryo and placentation 113:162 Successful implantation of embryo and placentation depend on proper trophoblast proliferation and differentiated into specialized invasive trophoblast. 26823725 4 39 theme invasive 583:590 arg1 trophoblasts 592:603 invasive trophoblasts 583:603 invasive trophoblasts 583:603 It has been identified that OPN is highly expressed in invasive trophoblasts in human placenta. 26823725 5 40 theme cell 746:749 arg1 lines 751:755 human choriocarcinoma cell lines 724:755 human choriocarcinoma cell lines of JAR and JEG-3 cells 724:778 In this study, we demonstrated that OPN is constitutively expressed in highly invasive phenotype of human choriocarcinoma cell lines of JAR and JEG-3 cells, and OPN could promote trophoblast proliferation and invasion, partly through promoting MMP-9 secretion. 26823725 2 41 theme regulatory 300:309 arg1 factors 311:317 regulatory factors 300:317 regulatory factors 300:317 However, little is known about the regulatory factors and mechanisms in trophoblast proliferation and differentiation. 26823725 2 42 from factors 311:317 arg1 trophoblast 337:347 trophoblast proliferation and differentiation 337:381 trophoblast proliferation and differentiation 337:381 However, little is known about the regulatory factors and mechanisms in trophoblast proliferation and differentiation. 26823725 5 43 theme lines 751:755 arg1 phenotype 711:719 highly invasive phenotype 695:719 highly invasive phenotype of human choriocarcinoma cell lines of JAR and JEG-3 cells 695:778 In this study, we demonstrated that OPN is constitutively expressed in highly invasive phenotype of human choriocarcinoma cell lines of JAR and JEG-3 cells, and OPN could promote trophoblast proliferation and invasion, partly through promoting MMP-9 secretion. 26823725 7 44 theme OPN 1031:1033 arg1 expression 1017:1026 the expression 1013:1026 the expression of OPN in trophoblast 1013:1048 Our data showed that the expression of OPN in trophoblast may participate in placentation, OPN expression defects may be involved in gestational trophoblastic diseases. 26823725 1 45 theme placentation 151:162 arg1 implantation 124:135 Successful implantation 113:135 Successful implantation of embryo and placentation 113:162 Successful implantation of embryo and placentation depend on proper trophoblast proliferation and differentiated into specialized invasive trophoblast. 26823725 0 46 theme matrix 76:81 arg1 metalloproteinase-9 83:101 matrix metalloproteinase-9 76:101 matrix metalloproteinase-9 76:101 Osteopontin facilitates invasion in human trophoblastic cells via promoting matrix metalloproteinase-9 in vitro. 26823725 2 47 from mechanisms 323:332 arg1 trophoblast 337:347 trophoblast proliferation and differentiation 337:381 trophoblast proliferation and differentiation 337:381 However, little is known about the regulatory factors and mechanisms in trophoblast proliferation and differentiation. 26823725 6 48 theme JEG-3 974:978 arg1 lines 985:989 JAR and JEG-3 cell lines 966:989 lines 985:989 Inhibition of OPN will compromise the abilities of proliferation and invasion in JAR and JEG-3 cell lines. 26823725 2 49 dep factors 311:317 arg1 the 296:298 the 296:298 the 296:298 However, little is known about the regulatory factors and mechanisms in trophoblast proliferation and differentiation. 26643118 4 0 theme °C. 817:819 arg1 microscopy 830:839 42 °C. Electron microscopy 814:839 42 °C. Electron microscopy 814:839 Whilst the amount of FlaB2 was similar for cells grown at < 35 °C, protein levels decreased at 38 °C and were barely detectable at 42 °C. Quantitative reverse transcription PCR experiments demonstrated that the flaB2 transcript levels were almost undetectable at 42 °C. Electron microscopy confirmed that the FlaB2 levels detected by Western blots corresponded to the state of archaellation, with cells grown at 42 °C being mostly non-archaellated. 26643118 3 1 theme archaellin 469:478 arg1 levels 486:491 major archaellin FlaB2 levels 463:491 major archaellin FlaB2 levels 463:491 Of the conditions tested, Western blot results showed that major archaellin FlaB2 levels only varied detectably as a result of growth temperature. 26643118 5 2 theme suggestive 1125:1134 arg1 °C 1121:1122 temperatures >38 °C 1104:1122 temperatures >38 °C 1104:1122 Unexpectedly, a lower apparent molecular mass for FlaB2 was observed in Western blots of cells grown at temperatures >38 °C, suggestive of a truncation in the attached N-linked tetrasaccharide at higher growth temperatures. 26643118 4 3 theme archaellation 928:940 arg1 state 919:923 the state 915:923 the state of archaellation 915:940 Whilst the amount of FlaB2 was similar for cells grown at < 35 °C, protein levels decreased at 38 °C and were barely detectable at 42 °C. Quantitative reverse transcription PCR experiments demonstrated that the flaB2 transcript levels were almost undetectable at 42 °C. Electron microscopy confirmed that the FlaB2 levels detected by Western blots corresponded to the state of archaellation, with cells grown at 42 °C being mostly non-archaellated. 26643118 5 4 theme Western 1072:1078 arg1 blots 1080:1084 Western blots 1072:1084 Western blots of cells grown at temperatures >38 °C, suggestive of a truncation in the attached N-linked tetrasaccharide at higher growth temperatures 1072:1221 Unexpectedly, a lower apparent molecular mass for FlaB2 was observed in Western blots of cells grown at temperatures >38 °C, suggestive of a truncation in the attached N-linked tetrasaccharide at higher growth temperatures. 26643118 4 5 theme 42 814:815 arg1 °C. 817:819 °C. 817:819 °C. 817:819 Whilst the amount of FlaB2 was similar for cells grown at < 35 °C, protein levels decreased at 38 °C and were barely detectable at 42 °C. Quantitative reverse transcription PCR experiments demonstrated that the flaB2 transcript levels were almost undetectable at 42 °C. Electron microscopy confirmed that the FlaB2 levels detected by Western blots corresponded to the state of archaellation, with cells grown at 42 °C being mostly non-archaellated. 26643118 1 6 from archaellation 147:159 arg1 maripaludis 178:188 Methanococcus maripaludis 164:188 Methanococcus maripaludis 164:188 In this study, the effects of growth conditions on archaellation in Methanococcus maripaludis were examined. 26643118 3 7 theme FlaB2 480:484 arg1 levels 486:491 major archaellin FlaB2 levels 463:491 major archaellin FlaB2 levels 463:491 Of the conditions tested, Western blot results showed that major archaellin FlaB2 levels only varied detectably as a result of growth temperature. 26643118 5 8 theme higher 1196:1201 arg1 temperatures 1210:1221 higher growth temperatures 1196:1221 higher growth temperatures 1196:1221 Unexpectedly, a lower apparent molecular mass for FlaB2 was observed in Western blots of cells grown at temperatures >38 °C, suggestive of a truncation in the attached N-linked tetrasaccharide at higher growth temperatures. 26643118 0 9 from Effects 0:6 arg1 archaellation 32:44 archaellation 32:44 archaellation 32:44 Effects of growth conditions on archaellation and N-glycosylation in Methanococcus maripaludis. 26643118 0 9 from Effects 0:6 arg1 N-glycosylation 50:64 N-glycosylation 50:64 N-glycosylation 50:64 Effects of growth conditions on archaellation and N-glycosylation in Methanococcus maripaludis. 26643118 6 10 located found 1439:1443 arg2 modifications 1425:1437 the attached threonine and acetamidino modifications 1386:1437 the attached threonine and acetamidino modifications found in the WT glycan 1386:1460 MS analysis of archaella isolated from cells grown at 40 °C confirmed that FlaB2 was now decorated with a trisaccharide in which the third sugar was also lacking the attached threonine and acetamidino modifications found in the WT glycan. 26643118 6 10 located found 1439:1443 arg1 glycan 1455:1460 the WT glycan 1448:1460 the WT glycan 1448:1460 MS analysis of archaella isolated from cells grown at 40 °C confirmed that FlaB2 was now decorated with a trisaccharide in which the third sugar was also lacking the attached threonine and acetamidino modifications found in the WT glycan. 26643118 4 11 theme Quantitative 689:700 arg1 experiments 728:738 Quantitative reverse transcription PCR experiments 689:738 Quantitative reverse transcription PCR experiments 689:738 Whilst the amount of FlaB2 was similar for cells grown at < 35 °C, protein levels decreased at 38 °C and were barely detectable at 42 °C. Quantitative reverse transcription PCR experiments demonstrated that the flaB2 transcript levels were almost undetectable at 42 °C. Electron microscopy confirmed that the FlaB2 levels detected by Western blots corresponded to the state of archaellation, with cells grown at 42 °C being mostly non-archaellated. 26643118 5 12 theme growth 1203:1208 arg1 temperatures 1210:1221 higher growth temperatures 1196:1221 higher growth temperatures 1196:1221 Unexpectedly, a lower apparent molecular mass for FlaB2 was observed in Western blots of cells grown at temperatures >38 °C, suggestive of a truncation in the attached N-linked tetrasaccharide at higher growth temperatures. 26643118 3 13 theme growth 531:536 arg1 temperature 538:548 growth temperature 531:548 growth temperature 531:548 Of the conditions tested, Western blot results showed that major archaellin FlaB2 levels only varied detectably as a result of growth temperature. 26643118 0 14 from N-glycosylation 50:64 arg1 maripaludis 83:93 Methanococcus maripaludis 69:93 Methanococcus maripaludis 69:93 Effects of growth conditions on archaellation and N-glycosylation in Methanococcus maripaludis. 26643118 4 15 theme Electron 821:828 arg1 microscopy 830:839 42 °C. Electron microscopy 814:839 42 °C. Electron microscopy 814:839 Whilst the amount of FlaB2 was similar for cells grown at < 35 °C, protein levels decreased at 38 °C and were barely detectable at 42 °C. Quantitative reverse transcription PCR experiments demonstrated that the flaB2 transcript levels were almost undetectable at 42 °C. Electron microscopy confirmed that the FlaB2 levels detected by Western blots corresponded to the state of archaellation, with cells grown at 42 °C being mostly non-archaellated. 26643118 5 16 theme truncation 1141:1150 arg1 suggestive 1125:1134 suggestive 1125:1134 suggestive 1125:1134 Unexpectedly, a lower apparent molecular mass for FlaB2 was observed in Western blots of cells grown at temperatures >38 °C, suggestive of a truncation in the attached N-linked tetrasaccharide at higher growth temperatures. 26643118 2 17 theme growth 383:388 arg1 temperatures 390:401 growth temperatures 383:401 growth temperatures 383:401 Cells were grown in a variety of media, including complex, minimal and with formate as the electron donor, with different nitrogen sources, varied salinities and at a variety of growth temperatures. 26643118 2 18 theme minimal 264:270 arg1 complex 255:261 complex 255:261 complex 255:261 Cells were grown in a variety of media, including complex, minimal and with formate as the electron donor, with different nitrogen sources, varied salinities and at a variety of growth temperatures. 26643118 3 19 theme Western 430:436 arg1 results 443:449 Western blot results 430:449 Western blot results 430:449 Of the conditions tested, Western blot results showed that major archaellin FlaB2 levels only varied detectably as a result of growth temperature. 26643118 0 20 from archaellation 32:44 arg1 maripaludis 83:93 Methanococcus maripaludis 69:93 Methanococcus maripaludis 69:93 Effects of growth conditions on archaellation and N-glycosylation in Methanococcus maripaludis. 26643118 4 21 theme reverse 702:708 arg1 experiments 728:738 Quantitative reverse transcription PCR experiments 689:738 Quantitative reverse transcription PCR experiments 689:738 Whilst the amount of FlaB2 was similar for cells grown at < 35 °C, protein levels decreased at 38 °C and were barely detectable at 42 °C. Quantitative reverse transcription PCR experiments demonstrated that the flaB2 transcript levels were almost undetectable at 42 °C. Electron microscopy confirmed that the FlaB2 levels detected by Western blots corresponded to the state of archaellation, with cells grown at 42 °C being mostly non-archaellated. 26643118 4 22 theme FlaB2 572:576 arg1 FlaB2 572:576 FlaB2 572:576 FlaB2 572:576 Whilst the amount of FlaB2 was similar for cells grown at < 35 °C, protein levels decreased at 38 °C and were barely detectable at 42 °C. Quantitative reverse transcription PCR experiments demonstrated that the flaB2 transcript levels were almost undetectable at 42 °C. Electron microscopy confirmed that the FlaB2 levels detected by Western blots corresponded to the state of archaellation, with cells grown at 42 °C being mostly non-archaellated. 26643118 4 22 theme FlaB2 572:576 arg1 amount 562:567 the amount 558:567 the amount of FlaB2 558:576 Whilst the amount of FlaB2 was similar for cells grown at < 35 °C, protein levels decreased at 38 °C and were barely detectable at 42 °C. Quantitative reverse transcription PCR experiments demonstrated that the flaB2 transcript levels were almost undetectable at 42 °C. Electron microscopy confirmed that the FlaB2 levels detected by Western blots corresponded to the state of archaellation, with cells grown at 42 °C being mostly non-archaellated. 26643118 4 22 theme FlaB2 572:576 arg1 similar 582:588 similar 582:588 similar 582:588 Whilst the amount of FlaB2 was similar for cells grown at < 35 °C, protein levels decreased at 38 °C and were barely detectable at 42 °C. Quantitative reverse transcription PCR experiments demonstrated that the flaB2 transcript levels were almost undetectable at 42 °C. Electron microscopy confirmed that the FlaB2 levels detected by Western blots corresponded to the state of archaellation, with cells grown at 42 °C being mostly non-archaellated. 26643118 5 23 link N-linked 1168:1175 arg1 tetrasaccharide 1177:1191 the attached N-linked tetrasaccharide 1155:1191 the attached N-linked tetrasaccharide 1155:1191 Unexpectedly, a lower apparent molecular mass for FlaB2 was observed in Western blots of cells grown at temperatures >38 °C, suggestive of a truncation in the attached N-linked tetrasaccharide at higher growth temperatures. 26643118 2 24 theme electron 296:303 arg1 donor 305:309 the electron donor 292:309 the electron donor 292:309 Cells were grown in a variety of media, including complex, minimal and with formate as the electron donor, with different nitrogen sources, varied salinities and at a variety of growth temperatures. 26643118 4 25 from °C. 685:687 arg1 detectable 668:677 detectable 668:677 detectable 668:677 Whilst the amount of FlaB2 was similar for cells grown at < 35 °C, protein levels decreased at 38 °C and were barely detectable at 42 °C. Quantitative reverse transcription PCR experiments demonstrated that the flaB2 transcript levels were almost undetectable at 42 °C. Electron microscopy confirmed that the FlaB2 levels detected by Western blots corresponded to the state of archaellation, with cells grown at 42 °C being mostly non-archaellated. 26643118 3 26 theme temperature 538:548 arg1 result 521:526 a result 519:526 a result of growth temperature 519:548 Of the conditions tested, Western blot results showed that major archaellin FlaB2 levels only varied detectably as a result of growth temperature. 26643118 5 27 from truncation 1141:1150 arg1 tetrasaccharide 1177:1191 the attached N-linked tetrasaccharide 1155:1191 the attached N-linked tetrasaccharide 1155:1191 Unexpectedly, a lower apparent molecular mass for FlaB2 was observed in Western blots of cells grown at temperatures >38 °C, suggestive of a truncation in the attached N-linked tetrasaccharide at higher growth temperatures. 26643118 6 28 theme MS 1224:1225 arg1 analysis 1227:1234 MS analysis 1224:1234 MS analysis of archaella isolated from cells grown at 40 °C 1224:1282 MS analysis of archaella isolated from cells grown at 40 °C confirmed that FlaB2 was now decorated with a trisaccharide in which the third sugar was also lacking the attached threonine and acetamidino modifications found in the WT glycan. 26643118 0 29 theme conditions 18:27 arg1 Effects 0:6 Effects 0:6 Effects of growth conditions on archaellation and N-glycosylation in Methanococcus maripaludis 0:93 Effects of growth conditions on archaellation and N-glycosylation in Methanococcus maripaludis. 26643118 1 30 from effects 115:121 arg1 archaellation 147:159 archaellation 147:159 archaellation in Methanococcus maripaludis 147:188 In this study, the effects of growth conditions on archaellation in Methanococcus maripaludis were examined. 26643118 5 31 from temperatures 1210:1221 arg1 truncation 1141:1150 a truncation 1139:1150 a truncation in the attached N-linked tetrasaccharide at higher growth temperatures 1139:1221 Unexpectedly, a lower apparent molecular mass for FlaB2 was observed in Western blots of cells grown at temperatures >38 °C, suggestive of a truncation in the attached N-linked tetrasaccharide at higher growth temperatures. 26643118 2 32 theme temperatures 390:401 arg1 variety 372:378 a variety 370:378 a variety of growth temperatures 370:401 Cells were grown in a variety of media, including complex, minimal and with formate as the electron donor, with different nitrogen sources, varied salinities and at a variety of growth temperatures. 26643118 2 32 theme temperatures 390:401 arg1 temperatures 390:401 growth temperatures 383:401 growth temperatures 383:401 Cells were grown in a variety of media, including complex, minimal and with formate as the electron donor, with different nitrogen sources, varied salinities and at a variety of growth temperatures. 26643118 0 33 theme growth 11:16 arg1 conditions 18:27 growth conditions 11:27 growth conditions 11:27 Effects of growth conditions on archaellation and N-glycosylation in Methanococcus maripaludis. 26643118 4 34 theme transcription 710:722 arg1 experiments 728:738 Quantitative reverse transcription PCR experiments 689:738 Quantitative reverse transcription PCR experiments 689:738 Whilst the amount of FlaB2 was similar for cells grown at < 35 °C, protein levels decreased at 38 °C and were barely detectable at 42 °C. Quantitative reverse transcription PCR experiments demonstrated that the flaB2 transcript levels were almost undetectable at 42 °C. Electron microscopy confirmed that the FlaB2 levels detected by Western blots corresponded to the state of archaellation, with cells grown at 42 °C being mostly non-archaellated. 26643118 2 35 theme nitrogen 327:334 arg1 sources 336:342 different nitrogen sources 317:342 different nitrogen sources 317:342 Cells were grown in a variety of media, including complex, minimal and with formate as the electron donor, with different nitrogen sources, varied salinities and at a variety of growth temperatures. 26643118 2 35 theme nitrogen 327:334 arg1 salinities 352:361 varied salinities 345:361 varied salinities 345:361 Cells were grown in a variety of media, including complex, minimal and with formate as the electron donor, with different nitrogen sources, varied salinities and at a variety of growth temperatures. 26643118 1 36 theme conditions 133:142 arg1 effects 115:121 the effects 111:121 the effects of growth conditions on archaellation in Methanococcus maripaludis 111:188 In this study, the effects of growth conditions on archaellation in Methanococcus maripaludis were examined. 26643118 5 37 located observed 1060:1067 arg2 mass 1041:1044 a lower apparent molecular mass 1014:1044 a lower apparent molecular mass for FlaB2 1014:1054 Unexpectedly, a lower apparent molecular mass for FlaB2 was observed in Western blots of cells grown at temperatures >38 °C, suggestive of a truncation in the attached N-linked tetrasaccharide at higher growth temperatures. 26643118 5 37 located observed 1060:1067 arg1 blots 1080:1084 Western blots 1072:1084 Western blots of cells grown at temperatures >38 °C, suggestive of a truncation in the attached N-linked tetrasaccharide at higher growth temperatures 1072:1221 Unexpectedly, a lower apparent molecular mass for FlaB2 was observed in Western blots of cells grown at temperatures >38 °C, suggestive of a truncation in the attached N-linked tetrasaccharide at higher growth temperatures. 26643118 4 38 theme Western 885:891 arg1 blots 893:897 Western blots 885:897 Western blots 885:897 Whilst the amount of FlaB2 was similar for cells grown at < 35 °C, protein levels decreased at 38 °C and were barely detectable at 42 °C. Quantitative reverse transcription PCR experiments demonstrated that the flaB2 transcript levels were almost undetectable at 42 °C. Electron microscopy confirmed that the FlaB2 levels detected by Western blots corresponded to the state of archaellation, with cells grown at 42 °C being mostly non-archaellated. 26643118 5 39 theme lower 1016:1020 arg1 mass 1041:1044 a lower apparent molecular mass 1014:1044 a lower apparent molecular mass for FlaB2 1014:1054 Unexpectedly, a lower apparent molecular mass for FlaB2 was observed in Western blots of cells grown at temperatures >38 °C, suggestive of a truncation in the attached N-linked tetrasaccharide at higher growth temperatures. 26643118 4 40 theme flaB2 762:766 arg1 undetectable 798:809 undetectable 798:809 undetectable 798:809 Whilst the amount of FlaB2 was similar for cells grown at < 35 °C, protein levels decreased at 38 °C and were barely detectable at 42 °C. Quantitative reverse transcription PCR experiments demonstrated that the flaB2 transcript levels were almost undetectable at 42 °C. Electron microscopy confirmed that the FlaB2 levels detected by Western blots corresponded to the state of archaellation, with cells grown at 42 °C being mostly non-archaellated. 26643118 4 40 theme flaB2 762:766 arg1 levels 779:784 the flaB2 transcript levels 758:784 the flaB2 transcript levels 758:784 Whilst the amount of FlaB2 was similar for cells grown at < 35 °C, protein levels decreased at 38 °C and were barely detectable at 42 °C. Quantitative reverse transcription PCR experiments demonstrated that the flaB2 transcript levels were almost undetectable at 42 °C. Electron microscopy confirmed that the FlaB2 levels detected by Western blots corresponded to the state of archaellation, with cells grown at 42 °C being mostly non-archaellated. 26643118 6 41 theme WT 1452:1453 arg1 glycan 1455:1460 the WT glycan 1448:1460 the WT glycan 1448:1460 MS analysis of archaella isolated from cells grown at 40 °C confirmed that FlaB2 was now decorated with a trisaccharide in which the third sugar was also lacking the attached threonine and acetamidino modifications found in the WT glycan. 26643118 5 42 theme apparent 1022:1029 arg1 mass 1041:1044 a lower apparent molecular mass 1014:1044 a lower apparent molecular mass for FlaB2 1014:1054 Unexpectedly, a lower apparent molecular mass for FlaB2 was observed in Western blots of cells grown at temperatures >38 °C, suggestive of a truncation in the attached N-linked tetrasaccharide at higher growth temperatures. 26643118 6 43 theme third 1357:1361 arg1 sugar 1363:1367 the third sugar 1353:1367 the third sugar 1353:1367 MS analysis of archaella isolated from cells grown at 40 °C confirmed that FlaB2 was now decorated with a trisaccharide in which the third sugar was also lacking the attached threonine and acetamidino modifications found in the WT glycan. 26643118 5 44 theme cells 1089:1093 arg1 blots 1080:1084 Western blots 1072:1084 Western blots of cells grown at temperatures >38 °C, suggestive of a truncation in the attached N-linked tetrasaccharide at higher growth temperatures 1072:1221 Unexpectedly, a lower apparent molecular mass for FlaB2 was observed in Western blots of cells grown at temperatures >38 °C, suggestive of a truncation in the attached N-linked tetrasaccharide at higher growth temperatures. 26643118 5 45 theme molecular 1031:1039 arg1 mass 1041:1044 a lower apparent molecular mass 1014:1044 a lower apparent molecular mass for FlaB2 1014:1054 Unexpectedly, a lower apparent molecular mass for FlaB2 was observed in Western blots of cells grown at temperatures >38 °C, suggestive of a truncation in the attached N-linked tetrasaccharide at higher growth temperatures. 26643118 6 46 theme archaella 1239:1247 arg1 analysis 1227:1234 MS analysis 1224:1234 MS analysis of archaella isolated from cells grown at 40 °C 1224:1282 MS analysis of archaella isolated from cells grown at 40 °C confirmed that FlaB2 was now decorated with a trisaccharide in which the third sugar was also lacking the attached threonine and acetamidino modifications found in the WT glycan. 26643118 2 47 theme different 317:325 arg1 sources 336:342 different nitrogen sources 317:342 different nitrogen sources 317:342 Cells were grown in a variety of media, including complex, minimal and with formate as the electron donor, with different nitrogen sources, varied salinities and at a variety of growth temperatures. 26643118 2 47 theme different 317:325 arg1 salinities 352:361 varied salinities 345:361 varied salinities 345:361 Cells were grown in a variety of media, including complex, minimal and with formate as the electron donor, with different nitrogen sources, varied salinities and at a variety of growth temperatures. 26643118 4 48 theme transcript 768:777 arg1 undetectable 798:809 undetectable 798:809 undetectable 798:809 Whilst the amount of FlaB2 was similar for cells grown at < 35 °C, protein levels decreased at 38 °C and were barely detectable at 42 °C. Quantitative reverse transcription PCR experiments demonstrated that the flaB2 transcript levels were almost undetectable at 42 °C. Electron microscopy confirmed that the FlaB2 levels detected by Western blots corresponded to the state of archaellation, with cells grown at 42 °C being mostly non-archaellated. 26643118 4 48 theme transcript 768:777 arg1 levels 779:784 the flaB2 transcript levels 758:784 the flaB2 transcript levels 758:784 Whilst the amount of FlaB2 was similar for cells grown at < 35 °C, protein levels decreased at 38 °C and were barely detectable at 42 °C. Quantitative reverse transcription PCR experiments demonstrated that the flaB2 transcript levels were almost undetectable at 42 °C. Electron microscopy confirmed that the FlaB2 levels detected by Western blots corresponded to the state of archaellation, with cells grown at 42 °C being mostly non-archaellated. 26643118 3 49 theme major 463:467 arg1 levels 486:491 major archaellin FlaB2 levels 463:491 major archaellin FlaB2 levels 463:491 Of the conditions tested, Western blot results showed that major archaellin FlaB2 levels only varied detectably as a result of growth temperature. 26643118 6 50 attach isolated 1249:1256 arg1 cells 1263:1267 cells 1263:1267 cells grown at 40 °C 1263:1282 MS analysis of archaella isolated from cells grown at 40 °C confirmed that FlaB2 was now decorated with a trisaccharide in which the third sugar was also lacking the attached threonine and acetamidino modifications found in the WT glycan. 26643118 6 50 attach isolated 1249:1256 arg2 archaella 1239:1247 archaella 1239:1247 archaella isolated from cells grown at 40 °C 1239:1282 MS analysis of archaella isolated from cells grown at 40 °C confirmed that FlaB2 was now decorated with a trisaccharide in which the third sugar was also lacking the attached threonine and acetamidino modifications found in the WT glycan. 26643118 0 51 gly N-glycosylation 50:64 arg1 maripaludis 83:93 Methanococcus maripaludis 69:93 Methanococcus maripaludis 69:93 Effects of growth conditions on archaellation and N-glycosylation in Methanococcus maripaludis. 26643118 4 52 theme FlaB2 860:864 arg1 levels 866:871 the FlaB2 levels 856:871 the FlaB2 levels detected by Western blots 856:897 Whilst the amount of FlaB2 was similar for cells grown at < 35 °C, protein levels decreased at 38 °C and were barely detectable at 42 °C. Quantitative reverse transcription PCR experiments demonstrated that the flaB2 transcript levels were almost undetectable at 42 °C. Electron microscopy confirmed that the FlaB2 levels detected by Western blots corresponded to the state of archaellation, with cells grown at 42 °C being mostly non-archaellated. 26643118 6 53 theme acetamidino 1413:1423 arg1 modifications 1425:1437 the attached threonine and acetamidino modifications 1386:1437 the attached threonine and acetamidino modifications found in the WT glycan 1386:1460 MS analysis of archaella isolated from cells grown at 40 °C confirmed that FlaB2 was now decorated with a trisaccharide in which the third sugar was also lacking the attached threonine and acetamidino modifications found in the WT glycan. 26643118 2 54 with minimal 264:270 arg1 sources 336:342 different nitrogen sources 317:342 different nitrogen sources 317:342 Cells were grown in a variety of media, including complex, minimal and with formate as the electron donor, with different nitrogen sources, varied salinities and at a variety of growth temperatures. 26643118 2 54 with minimal 264:270 arg1 salinities 352:361 varied salinities 345:361 varied salinities 345:361 Cells were grown in a variety of media, including complex, minimal and with formate as the electron donor, with different nitrogen sources, varied salinities and at a variety of growth temperatures. 26643118 2 54 with minimal 264:270 arg1 formate 281:287 formate 281:287 formate as the electron donor 281:309 Cells were grown in a variety of media, including complex, minimal and with formate as the electron donor, with different nitrogen sources, varied salinities and at a variety of growth temperatures. 26643118 4 55 theme PCR 724:726 arg1 experiments 728:738 Quantitative reverse transcription PCR experiments 689:738 Quantitative reverse transcription PCR experiments 689:738 Whilst the amount of FlaB2 was similar for cells grown at < 35 °C, protein levels decreased at 38 °C and were barely detectable at 42 °C. Quantitative reverse transcription PCR experiments demonstrated that the flaB2 transcript levels were almost undetectable at 42 °C. Electron microscopy confirmed that the FlaB2 levels detected by Western blots corresponded to the state of archaellation, with cells grown at 42 °C being mostly non-archaellated. 26643118 1 56 theme growth 126:131 arg1 conditions 133:142 growth conditions 126:142 growth conditions 126:142 In this study, the effects of growth conditions on archaellation in Methanococcus maripaludis were examined. 26643118 3 57 theme blot 438:441 arg1 results 443:449 Western blot results 430:449 Western blot results 430:449 Of the conditions tested, Western blot results showed that major archaellin FlaB2 levels only varied detectably as a result of growth temperature. 26643118 2 58 from variety 372:378 arg1 minimal 264:270 minimal 264:270 minimal 264:270 Cells were grown in a variety of media, including complex, minimal and with formate as the electron donor, with different nitrogen sources, varied salinities and at a variety of growth temperatures. 26643118 2 59 theme varied 345:350 arg1 sources 336:342 different nitrogen sources 317:342 different nitrogen sources 317:342 Cells were grown in a variety of media, including complex, minimal and with formate as the electron donor, with different nitrogen sources, varied salinities and at a variety of growth temperatures. 26643118 2 59 theme varied 345:350 arg1 salinities 352:361 varied salinities 345:361 varied salinities 345:361 Cells were grown in a variety of media, including complex, minimal and with formate as the electron donor, with different nitrogen sources, varied salinities and at a variety of growth temperatures. 26643118 6 60 theme threonine 1399:1407 arg1 modifications 1425:1437 the attached threonine and acetamidino modifications 1386:1437 the attached threonine and acetamidino modifications found in the WT glycan 1386:1460 MS analysis of archaella isolated from cells grown at 40 °C confirmed that FlaB2 was now decorated with a trisaccharide in which the third sugar was also lacking the attached threonine and acetamidino modifications found in the WT glycan. 26643118 5 61 theme attached 1159:1166 arg1 tetrasaccharide 1177:1191 the attached N-linked tetrasaccharide 1155:1191 the attached N-linked tetrasaccharide 1155:1191 Unexpectedly, a lower apparent molecular mass for FlaB2 was observed in Western blots of cells grown at temperatures >38 °C, suggestive of a truncation in the attached N-linked tetrasaccharide at higher growth temperatures. 26643118 2 62 theme media 238:242 arg1 variety 227:233 a variety 225:233 a variety 225:233 Cells were grown in a variety of media, including complex, minimal and with formate as the electron donor, with different nitrogen sources, varied salinities and at a variety of growth temperatures. 26643118 2 62 theme media 238:242 arg1 media 238:242 media 238:242 media 238:242 Cells were grown in a variety of media, including complex, minimal and with formate as the electron donor, with different nitrogen sources, varied salinities and at a variety of growth temperatures. 26643118 2 62 theme media 238:242 arg1 complex 255:261 complex 255:261 complex 255:261 Cells were grown in a variety of media, including complex, minimal and with formate as the electron donor, with different nitrogen sources, varied salinities and at a variety of growth temperatures. 26643118 4 63 theme protein 618:624 arg1 levels 626:631 protein levels 618:631 protein levels 618:631 Whilst the amount of FlaB2 was similar for cells grown at < 35 °C, protein levels decreased at 38 °C and were barely detectable at 42 °C. Quantitative reverse transcription PCR experiments demonstrated that the flaB2 transcript levels were almost undetectable at 42 °C. Electron microscopy confirmed that the FlaB2 levels detected by Western blots corresponded to the state of archaellation, with cells grown at 42 °C being mostly non-archaellated. 26643118 6 64 theme attached 1390:1397 arg1 modifications 1425:1437 the attached threonine and acetamidino modifications 1386:1437 the attached threonine and acetamidino modifications found in the WT glycan 1386:1460 MS analysis of archaella isolated from cells grown at 40 °C confirmed that FlaB2 was now decorated with a trisaccharide in which the third sugar was also lacking the attached threonine and acetamidino modifications found in the WT glycan. 26643118 5 65 theme N-linked 1168:1175 arg1 tetrasaccharide 1177:1191 the attached N-linked tetrasaccharide 1155:1191 the attached N-linked tetrasaccharide 1155:1191 Unexpectedly, a lower apparent molecular mass for FlaB2 was observed in Western blots of cells grown at temperatures >38 °C, suggestive of a truncation in the attached N-linked tetrasaccharide at higher growth temperatures. 25379385 8 0 theme N-glycosylation 1039:1053 arg1 defect 1029:1034 the defect 1025:1034 the defect of N-glycosylation in ECM1 1025:1061 These results indicate that the defect of N-glycosylation in ECM1 is not involved in the aberration of secretion of LP-derived mutated ECM1. 25379385 5 1 from defective 646:654 arg1 sites 681:685 these N-glycosylation sites 659:685 these N-glycosylation sites 659:685 As ECM1 has three putative N-glycosylation sites and most of mutated ECM1 observed in LP patients are defective in these N-glycosylation sites, we investigated the correlation between LP and N-glycosylation of ECM1. 25379385 8 2 theme mutated 1124:1130 arg1 ECM1 1132:1135 LP-derived mutated ECM1 1113:1135 LP-derived mutated ECM1 1113:1135 These results indicate that the defect of N-glycosylation in ECM1 is not involved in the aberration of secretion of LP-derived mutated ECM1. 25379385 1 3 theme important 214:222 arg1 roles 224:228 important roles 214:228 important roles 214:228 Extracellular matrix protein 1 (ECM1) is expressed in a wide variety of tissues and plays important roles in extracellular matrix formation. 25379385 4 4 located observed 480:487 arg2 mutation 471:478 ECM1 gene mutation 461:478 ECM1 gene mutation observed in LP patients 461:502 Here, we showed that ECM1 gene mutation observed in LP patients significantly suppresses its secretion. 25379385 4 4 located observed 480:487 arg1 patients 495:502 LP patients 492:502 LP patients 492:502 Here, we showed that ECM1 gene mutation observed in LP patients significantly suppresses its secretion. 25379385 5 5 gly N-glycosylation 665:679 arg2 sites 681:685 these N-glycosylation sites 659:685 these N-glycosylation sites 659:685 As ECM1 has three putative N-glycosylation sites and most of mutated ECM1 observed in LP patients are defective in these N-glycosylation sites, we investigated the correlation between LP and N-glycosylation of ECM1. 25379385 5 6 theme mutated 605:611 arg1 ECM1 613:616 mutated ECM1 605:616 mutated ECM1 observed in LP patients 605:640 As ECM1 has three putative N-glycosylation sites and most of mutated ECM1 observed in LP patients are defective in these N-glycosylation sites, we investigated the correlation between LP and N-glycosylation of ECM1. 25379385 6 7 gly N-glycosylated 827:840 arg1 N-glycosylated 827:840 N-glycosylated 827:840 N-glycosylated 827:840 We identified that the Asn(354) and Asn(444) residues in ECM1 were N-glycosylated by mass spectrometry analysis. 25379385 6 7 gly N-glycosylated 827:840 arg1 residues 805:812 the Asn(354) and Asn(444) residues 779:812 the Asn(354) and Asn(444) residues in ECM1 779:820 We identified that the Asn(354) and Asn(444) residues in ECM1 were N-glycosylated by mass spectrometry analysis. 25379385 7 8 theme patient-derived 972:986 arg1 mutants 988:994 LP patient-derived mutants 969:994 LP patient-derived mutants 969:994 In addition, an N-linked glycan at Asn(354) negatively regulated secretion of ECM1, contrary to LP patient-derived mutants. 25379385 3 9 theme LP 417:418 arg1 approach 405:412 an effective therapeutic approach 380:412 an effective therapeutic approach of LP 380:418 However, an effective therapeutic approach of LP is not established. 25379385 7 10 link patient-derived 972:986 arg1 mutants 988:994 LP patient-derived mutants 969:994 LP patient-derived mutants 969:994 In addition, an N-linked glycan at Asn(354) negatively regulated secretion of ECM1, contrary to LP patient-derived mutants. 25379385 5 11 contain has 552:554 arg2 sites 587:591 three putative N-glycosylation sites 556:591 three putative N-glycosylation sites 556:591 As ECM1 has three putative N-glycosylation sites and most of mutated ECM1 observed in LP patients are defective in these N-glycosylation sites, we investigated the correlation between LP and N-glycosylation of ECM1. 25379385 5 11 contain has 552:554 arg1 ECM1 547:550 ECM1 547:550 ECM1 547:550 As ECM1 has three putative N-glycosylation sites and most of mutated ECM1 observed in LP patients are defective in these N-glycosylation sites, we investigated the correlation between LP and N-glycosylation of ECM1. 25379385 5 12 theme putative 562:569 arg1 sites 587:591 three putative N-glycosylation sites 556:591 three putative N-glycosylation sites 556:591 As ECM1 has three putative N-glycosylation sites and most of mutated ECM1 observed in LP patients are defective in these N-glycosylation sites, we investigated the correlation between LP and N-glycosylation of ECM1. 25379385 2 13 theme skin 337:340 arg1 condition 342:350 a rare skin condition 330:350 a rare skin condition of genetic origin 330:368 Additionally, ECM1 gene mutations cause lipoid proteinosis (LP), a rare skin condition of genetic origin. 25379385 2 13 theme skin 337:340 arg1 proteinosis 312:322 lipoid proteinosis 305:322 lipoid proteinosis (LP) 305:327 Additionally, ECM1 gene mutations cause lipoid proteinosis (LP), a rare skin condition of genetic origin. 25379385 6 14 theme Asn 796:798 arg1 N-glycosylated 827:840 N-glycosylated 827:840 N-glycosylated 827:840 We identified that the Asn(354) and Asn(444) residues in ECM1 were N-glycosylated by mass spectrometry analysis. 25379385 6 14 theme Asn 796:798 arg1 residues 805:812 the Asn(354) and Asn(444) residues 779:812 the Asn(354) and Asn(444) residues in ECM1 779:820 We identified that the Asn(354) and Asn(444) residues in ECM1 were N-glycosylated by mass spectrometry analysis. 25379385 5 15 theme N-glycosylation 571:585 arg1 sites 587:591 three putative N-glycosylation sites 556:591 three putative N-glycosylation sites 556:591 As ECM1 has three putative N-glycosylation sites and most of mutated ECM1 observed in LP patients are defective in these N-glycosylation sites, we investigated the correlation between LP and N-glycosylation of ECM1. 25379385 2 16 theme gene 284:287 arg1 mutations 289:297 ECM1 gene mutations 279:297 ECM1 gene mutations 279:297 Additionally, ECM1 gene mutations cause lipoid proteinosis (LP), a rare skin condition of genetic origin. 25379385 2 17 theme rare 332:335 arg1 condition 342:350 a rare skin condition 330:350 a rare skin condition of genetic origin 330:368 Additionally, ECM1 gene mutations cause lipoid proteinosis (LP), a rare skin condition of genetic origin. 25379385 2 17 theme rare 332:335 arg1 proteinosis 312:322 lipoid proteinosis 305:322 lipoid proteinosis (LP) 305:327 Additionally, ECM1 gene mutations cause lipoid proteinosis (LP), a rare skin condition of genetic origin. 25379385 5 18 theme ECM1 754:757 arg1 N-glycosylation 735:749 N-glycosylation 735:749 N-glycosylation of ECM1 735:757 As ECM1 has three putative N-glycosylation sites and most of mutated ECM1 observed in LP patients are defective in these N-glycosylation sites, we investigated the correlation between LP and N-glycosylation of ECM1. 25379385 5 18 theme ECM1 754:757 arg1 LP 728:729 LP 728:729 LP 728:729 As ECM1 has three putative N-glycosylation sites and most of mutated ECM1 observed in LP patients are defective in these N-glycosylation sites, we investigated the correlation between LP and N-glycosylation of ECM1. 25379385 1 19 theme extracellular 233:245 arg1 formation 254:262 extracellular matrix formation 233:262 extracellular matrix formation 233:262 Extracellular matrix protein 1 (ECM1) is expressed in a wide variety of tissues and plays important roles in extracellular matrix formation. 25379385 7 20 theme LP 969:970 arg1 mutants 988:994 LP patient-derived mutants 969:994 LP patient-derived mutants 969:994 In addition, an N-linked glycan at Asn(354) negatively regulated secretion of ECM1, contrary to LP patient-derived mutants. 25379385 2 21 theme ECM1 279:282 arg1 mutations 289:297 ECM1 gene mutations 279:297 ECM1 gene mutations 279:297 Additionally, ECM1 gene mutations cause lipoid proteinosis (LP), a rare skin condition of genetic origin. 25379385 5 22 located observed 618:625 arg2 ECM1 613:616 mutated ECM1 605:616 mutated ECM1 observed in LP patients 605:640 As ECM1 has three putative N-glycosylation sites and most of mutated ECM1 observed in LP patients are defective in these N-glycosylation sites, we investigated the correlation between LP and N-glycosylation of ECM1. 25379385 5 22 located observed 618:625 arg1 patients 633:640 LP patients 630:640 LP patients 630:640 As ECM1 has three putative N-glycosylation sites and most of mutated ECM1 observed in LP patients are defective in these N-glycosylation sites, we investigated the correlation between LP and N-glycosylation of ECM1. 25379385 8 23 theme ECM1 1132:1135 arg1 secretion 1100:1108 secretion 1100:1108 secretion of LP-derived mutated ECM1 1100:1135 These results indicate that the defect of N-glycosylation in ECM1 is not involved in the aberration of secretion of LP-derived mutated ECM1. 25379385 0 24 theme matrix 33:38 arg1 protein 40:46 extracellular matrix protein 1 19:48 extracellular matrix protein 1 (ECM1) 19:55 N-Glycosylation of extracellular matrix protein 1 (ECM1) regulates its secretion, which is unrelated to lipoid proteinosis. 25379385 0 24 theme matrix 33:38 arg1 ECM1 51:54 ECM1 51:54 ECM1 51:54 N-Glycosylation of extracellular matrix protein 1 (ECM1) regulates its secretion, which is unrelated to lipoid proteinosis. 25379385 1 25 theme matrix 247:252 arg1 formation 254:262 extracellular matrix formation 233:262 extracellular matrix formation 233:262 Extracellular matrix protein 1 (ECM1) is expressed in a wide variety of tissues and plays important roles in extracellular matrix formation. 25379385 0 26 theme lipoid 104:109 arg1 proteinosis 111:121 lipoid proteinosis 104:121 lipoid proteinosis 104:121 N-Glycosylation of extracellular matrix protein 1 (ECM1) regulates its secretion, which is unrelated to lipoid proteinosis. 25379385 0 27 theme extracellular 19:31 arg1 protein 40:46 extracellular matrix protein 1 19:48 extracellular matrix protein 1 (ECM1) 19:55 N-Glycosylation of extracellular matrix protein 1 (ECM1) regulates its secretion, which is unrelated to lipoid proteinosis. 25379385 0 27 theme extracellular 19:31 arg1 ECM1 51:54 ECM1 51:54 ECM1 51:54 N-Glycosylation of extracellular matrix protein 1 (ECM1) regulates its secretion, which is unrelated to lipoid proteinosis. 25379385 7 28 link N-linked 889:896 arg1 glycan 898:903 an N-linked glycan 886:903 an N-linked glycan at Asn(354) 886:915 In addition, an N-linked glycan at Asn(354) negatively regulated secretion of ECM1, contrary to LP patient-derived mutants. 25379385 5 29 from sites 681:685 arg1 defective 646:654 defective 646:654 defective 646:654 As ECM1 has three putative N-glycosylation sites and most of mutated ECM1 observed in LP patients are defective in these N-glycosylation sites, we investigated the correlation between LP and N-glycosylation of ECM1. 25379385 2 30 theme origin 363:368 arg1 condition 342:350 a rare skin condition 330:350 a rare skin condition of genetic origin 330:368 Additionally, ECM1 gene mutations cause lipoid proteinosis (LP), a rare skin condition of genetic origin. 25379385 2 30 theme origin 363:368 arg1 proteinosis 312:322 lipoid proteinosis 305:322 lipoid proteinosis (LP) 305:327 Additionally, ECM1 gene mutations cause lipoid proteinosis (LP), a rare skin condition of genetic origin. 25379385 7 31 from Asn 908:910 arg1 glycan 898:903 an N-linked glycan 886:903 an N-linked glycan at Asn(354) 886:915 In addition, an N-linked glycan at Asn(354) negatively regulated secretion of ECM1, contrary to LP patient-derived mutants. 25379385 4 32 theme LP 492:493 arg1 patients 495:502 LP patients 492:502 LP patients 492:502 Here, we showed that ECM1 gene mutation observed in LP patients significantly suppresses its secretion. 25379385 3 33 theme therapeutic 393:403 arg1 approach 405:412 an effective therapeutic approach 380:412 an effective therapeutic approach of LP 380:418 However, an effective therapeutic approach of LP is not established. 25379385 0 34 gly N-Glycosylation 0:14 arg1 protein 40:46 extracellular matrix protein 1 19:48 extracellular matrix protein 1 (ECM1) 19:55 N-Glycosylation of extracellular matrix protein 1 (ECM1) regulates its secretion, which is unrelated to lipoid proteinosis. 25379385 0 34 gly N-Glycosylation 0:14 arg1 ECM1 51:54 ECM1 51:54 ECM1 51:54 N-Glycosylation of extracellular matrix protein 1 (ECM1) regulates its secretion, which is unrelated to lipoid proteinosis. 25379385 2 35 theme genetic 355:361 arg1 origin 363:368 genetic origin 355:368 genetic origin 355:368 Additionally, ECM1 gene mutations cause lipoid proteinosis (LP), a rare skin condition of genetic origin. 25379385 0 36 theme protein 40:46 arg1 N-Glycosylation 0:14 N-Glycosylation 0:14 N-Glycosylation of extracellular matrix protein 1 (ECM1) 0:55 N-Glycosylation of extracellular matrix protein 1 (ECM1) regulates its secretion, which is unrelated to lipoid proteinosis. 25379385 4 37 theme ECM1 461:464 arg1 mutation 471:478 ECM1 gene mutation 461:478 ECM1 gene mutation observed in LP patients 461:502 Here, we showed that ECM1 gene mutation observed in LP patients significantly suppresses its secretion. 25379385 7 38 theme ECM1 951:954 arg1 secretion 938:946 secretion 938:946 secretion of ECM1 938:954 In addition, an N-linked glycan at Asn(354) negatively regulated secretion of ECM1, contrary to LP patient-derived mutants. 25379385 1 39 theme wide 180:183 arg1 tissues 196:202 tissues 196:202 tissues 196:202 Extracellular matrix protein 1 (ECM1) is expressed in a wide variety of tissues and plays important roles in extracellular matrix formation. 25379385 1 39 theme wide 180:183 arg1 variety 185:191 a wide variety 178:191 a wide variety of tissues 178:202 Extracellular matrix protein 1 (ECM1) is expressed in a wide variety of tissues and plays important roles in extracellular matrix formation. 25379385 6 40 theme spectrometry 850:861 arg1 analysis 863:870 mass spectrometry analysis 845:870 mass spectrometry analysis 845:870 We identified that the Asn(354) and Asn(444) residues in ECM1 were N-glycosylated by mass spectrometry analysis. 25379385 8 41 link LP-derived 1113:1122 arg1 ECM1 1132:1135 LP-derived mutated ECM1 1113:1135 LP-derived mutated ECM1 1113:1135 These results indicate that the defect of N-glycosylation in ECM1 is not involved in the aberration of secretion of LP-derived mutated ECM1. 25379385 8 42 theme secretion 1100:1108 arg1 aberration 1086:1095 the aberration 1082:1095 the aberration of secretion of LP-derived mutated ECM1 1082:1135 These results indicate that the defect of N-glycosylation in ECM1 is not involved in the aberration of secretion of LP-derived mutated ECM1. 25379385 6 43 theme Asn 783:785 arg1 N-glycosylated 827:840 N-glycosylated 827:840 N-glycosylated 827:840 We identified that the Asn(354) and Asn(444) residues in ECM1 were N-glycosylated by mass spectrometry analysis. 25379385 6 43 theme Asn 783:785 arg1 residues 805:812 the Asn(354) and Asn(444) residues 779:812 the Asn(354) and Asn(444) residues in ECM1 779:820 We identified that the Asn(354) and Asn(444) residues in ECM1 were N-glycosylated by mass spectrometry analysis. 25379385 2 44 theme lipoid 305:310 arg1 LP 325:326 LP 325:326 LP 325:326 Additionally, ECM1 gene mutations cause lipoid proteinosis (LP), a rare skin condition of genetic origin. 25379385 2 44 theme lipoid 305:310 arg1 proteinosis 312:322 lipoid proteinosis 305:322 lipoid proteinosis (LP) 305:327 Additionally, ECM1 gene mutations cause lipoid proteinosis (LP), a rare skin condition of genetic origin. 25379385 2 44 theme lipoid 305:310 arg1 condition 342:350 a rare skin condition 330:350 a rare skin condition of genetic origin 330:368 Additionally, ECM1 gene mutations cause lipoid proteinosis (LP), a rare skin condition of genetic origin. 25379385 4 45 theme gene 466:469 arg1 mutation 471:478 ECM1 gene mutation 461:478 ECM1 gene mutation observed in LP patients 461:502 Here, we showed that ECM1 gene mutation observed in LP patients significantly suppresses its secretion. 25379385 5 46 theme LP 630:631 arg1 patients 633:640 LP patients 630:640 LP patients 630:640 As ECM1 has three putative N-glycosylation sites and most of mutated ECM1 observed in LP patients are defective in these N-glycosylation sites, we investigated the correlation between LP and N-glycosylation of ECM1. 25379385 7 47 theme N-linked 889:896 arg1 glycan 898:903 an N-linked glycan 886:903 an N-linked glycan at Asn(354) 886:915 In addition, an N-linked glycan at Asn(354) negatively regulated secretion of ECM1, contrary to LP patient-derived mutants. 25379385 8 48 from defect 1029:1034 arg1 ECM1 1058:1061 ECM1 1058:1061 ECM1 1058:1061 These results indicate that the defect of N-glycosylation in ECM1 is not involved in the aberration of secretion of LP-derived mutated ECM1. 25379385 5 49 gly N-glycosylation 571:585 arg2 three 556:560 three 556:560 three 556:560 As ECM1 has three putative N-glycosylation sites and most of mutated ECM1 observed in LP patients are defective in these N-glycosylation sites, we investigated the correlation between LP and N-glycosylation of ECM1. 25379385 5 49 gly N-glycosylation 571:585 arg2 sites 587:591 three putative N-glycosylation sites 556:591 three putative N-glycosylation sites 556:591 As ECM1 has three putative N-glycosylation sites and most of mutated ECM1 observed in LP patients are defective in these N-glycosylation sites, we investigated the correlation between LP and N-glycosylation of ECM1. 25379385 5 50 gly N-glycosylation 735:749 arg1 ECM1 754:757 ECM1 754:757 ECM1 754:757 As ECM1 has three putative N-glycosylation sites and most of mutated ECM1 observed in LP patients are defective in these N-glycosylation sites, we investigated the correlation between LP and N-glycosylation of ECM1. 25379385 1 51 theme Extracellular 124:136 arg1 protein 145:151 Extracellular matrix protein 1 124:153 Extracellular matrix protein 1 (ECM1) 124:160 Extracellular matrix protein 1 (ECM1) is expressed in a wide variety of tissues and plays important roles in extracellular matrix formation. 25379385 1 51 theme Extracellular 124:136 arg1 ECM1 156:159 ECM1 156:159 ECM1 156:159 Extracellular matrix protein 1 (ECM1) is expressed in a wide variety of tissues and plays important roles in extracellular matrix formation. 25379385 3 52 theme effective 383:391 arg1 approach 405:412 an effective therapeutic approach 380:412 an effective therapeutic approach of LP 380:418 However, an effective therapeutic approach of LP is not established. 25379385 1 53 theme tissues 196:202 arg1 tissues 196:202 tissues 196:202 tissues 196:202 Extracellular matrix protein 1 (ECM1) is expressed in a wide variety of tissues and plays important roles in extracellular matrix formation. 25379385 1 53 theme tissues 196:202 arg1 variety 185:191 a wide variety 178:191 a wide variety of tissues 178:202 Extracellular matrix protein 1 (ECM1) is expressed in a wide variety of tissues and plays important roles in extracellular matrix formation. 25379385 6 54 from residues 805:812 arg1 ECM1 817:820 ECM1 817:820 ECM1 817:820 We identified that the Asn(354) and Asn(444) residues in ECM1 were N-glycosylated by mass spectrometry analysis. 25379385 8 55 theme LP-derived 1113:1122 arg1 ECM1 1132:1135 LP-derived mutated ECM1 1113:1135 LP-derived mutated ECM1 1113:1135 These results indicate that the defect of N-glycosylation in ECM1 is not involved in the aberration of secretion of LP-derived mutated ECM1. 25379385 1 56 theme matrix 138:143 arg1 protein 145:151 Extracellular matrix protein 1 124:153 Extracellular matrix protein 1 (ECM1) 124:160 Extracellular matrix protein 1 (ECM1) is expressed in a wide variety of tissues and plays important roles in extracellular matrix formation. 25379385 1 56 theme matrix 138:143 arg1 ECM1 156:159 ECM1 156:159 ECM1 156:159 Extracellular matrix protein 1 (ECM1) is expressed in a wide variety of tissues and plays important roles in extracellular matrix formation. 25379385 6 57 theme mass 845:848 arg1 spectrometry 850:861 mass spectrometry 845:861 mass spectrometry analysis 845:870 We identified that the Asn(354) and Asn(444) residues in ECM1 were N-glycosylated by mass spectrometry analysis. 25379385 5 58 theme N-glycosylation 665:679 arg1 sites 681:685 these N-glycosylation sites 659:685 these N-glycosylation sites 659:685 As ECM1 has three putative N-glycosylation sites and most of mutated ECM1 observed in LP patients are defective in these N-glycosylation sites, we investigated the correlation between LP and N-glycosylation of ECM1. 25036124 0 0 theme enzyme 74:79 arg1 activity 81:88 enzyme activity 74:88 enzyme activity 74:88 Crystal structure of α-amylase from Oryza sativa: molecular insights into enzyme activity and thermostability. 25036124 4 1 from α-amylases 544:553 arg1 hydrolase 572:580 the glycoside hydrolase family-13 558:590 the glycoside hydrolase family-13 558:590 The structure consists of a typical (β/α)8-barrel, which is well-conserved among most α-amylases in the glycoside hydrolase family-13. 25036124 5 2 theme Structural 593:602 arg1 superimposition 604:618 Structural superimposition 593:618 Structural superimposition 593:618 Structural superimposition indicated small variations in the catalytic domain and carbohydrate-binding sites between AmyI-1 and barley α-amylases. 25036124 1 3 from sativa 145:150 arg1 AmyI-1 111:116 AmyI-1 111:116 AmyI-1 111:116 AmyI-1 is an α-amylase from Oryza sativa (rice) and plays a crucial role in degrading starch in various tissues and at various growth stages. 25036124 1 3 from sativa 145:150 arg1 α-amylase 124:132 an α-amylase 121:132 an α-amylase from Oryza sativa (rice) 121:157 AmyI-1 is an α-amylase from Oryza sativa (rice) and plays a crucial role in degrading starch in various tissues and at various growth stages. 25036124 6 4 theme acid 839:842 arg1 residues 844:851 amino acid residues 833:851 amino acid residues 833:851 By contrast, regions around the N-linked glycosylation sites displayed lower conservation of amino acid residues, including Asn-263, Asn-265, Thr-307, Asn-342, Pro-373, and Ala-374 in AmyI-1, which are not conserved in barley α-amylases, suggesting that these residues may contribute to the construction of the structure of glycosylated AmyI-1. 25036124 6 4 theme acid 839:842 arg1 Pro-373 900:906 Pro-373 900:906 Pro-373 900:906 By contrast, regions around the N-linked glycosylation sites displayed lower conservation of amino acid residues, including Asn-263, Asn-265, Thr-307, Asn-342, Pro-373, and Ala-374 in AmyI-1, which are not conserved in barley α-amylases, suggesting that these residues may contribute to the construction of the structure of glycosylated AmyI-1. 25036124 6 4 theme acid 839:842 arg1 Ala-374 913:919 Ala-374 913:919 Ala-374 913:919 By contrast, regions around the N-linked glycosylation sites displayed lower conservation of amino acid residues, including Asn-263, Asn-265, Thr-307, Asn-342, Pro-373, and Ala-374 in AmyI-1, which are not conserved in barley α-amylases, suggesting that these residues may contribute to the construction of the structure of glycosylated AmyI-1. 25036124 7 5 theme functions 1158:1166 arg1 understanding 1126:1138 our understanding 1122:1138 our understanding of the biological functions of AmyI-1 1122:1176 These results increase the depths of our understanding of the biological functions of AmyI-1. 25036124 7 6 theme AmyI-1 1171:1176 arg1 functions 1158:1166 the biological functions 1143:1166 the biological functions of AmyI-1 1143:1176 These results increase the depths of our understanding of the biological functions of AmyI-1. 25036124 2 7 with glycoprotein 270:281 arg1 characteristic 335:348 a unique characteristic 326:348 a unique characteristic among plant α-amylases 326:371 This enzyme is a glycoprotein with an N-glycosylated carbohydrate chain, a unique characteristic among plant α-amylases. 25036124 2 7 with glycoprotein 270:281 arg1 chain 319:323 an N-glycosylated carbohydrate chain 288:323 an N-glycosylated carbohydrate chain 288:323 This enzyme is a glycoprotein with an N-glycosylated carbohydrate chain, a unique characteristic among plant α-amylases. 25036124 7 8 theme biological 1147:1156 arg1 functions 1158:1166 the biological functions 1143:1166 the biological functions of AmyI-1 1143:1176 These results increase the depths of our understanding of the biological functions of AmyI-1. 25036124 5 9 theme small 630:634 arg1 variations 636:645 small variations 630:645 small variations in the catalytic domain and carbohydrate-binding sites between AmyI-1 and barley α-amylases 630:737 Structural superimposition indicated small variations in the catalytic domain and carbohydrate-binding sites between AmyI-1 and barley α-amylases. 25036124 6 10 theme glycosylation 781:793 arg1 sites 795:799 the N-linked glycosylation sites 768:799 the N-linked glycosylation sites 768:799 By contrast, regions around the N-linked glycosylation sites displayed lower conservation of amino acid residues, including Asn-263, Asn-265, Thr-307, Asn-342, Pro-373, and Ala-374 in AmyI-1, which are not conserved in barley α-amylases, suggesting that these residues may contribute to the construction of the structure of glycosylated AmyI-1. 25036124 1 11 theme various 230:236 arg1 stages 245:250 various growth stages 230:250 various growth stages 230:250 AmyI-1 is an α-amylase from Oryza sativa (rice) and plays a crucial role in degrading starch in various tissues and at various growth stages. 25036124 0 12 from sativa 42:47 arg1 structure 8:16 Crystal structure 0:16 Crystal structure of α-amylase from Oryza sativa: molecular insights into enzyme activity and thermostability. 0:109 Crystal structure of α-amylase from Oryza sativa: molecular insights into enzyme activity and thermostability. 25036124 4 13 theme glycoside 562:570 arg1 hydrolase 572:580 the glycoside hydrolase family-13 558:590 the glycoside hydrolase family-13 558:590 The structure consists of a typical (β/α)8-barrel, which is well-conserved among most α-amylases in the glycoside hydrolase family-13. 25036124 5 14 theme barley 721:726 arg1 α-amylases 728:737 barley α-amylases 721:737 barley α-amylases 721:737 Structural superimposition indicated small variations in the catalytic domain and carbohydrate-binding sites between AmyI-1 and barley α-amylases. 25036124 6 15 theme AmyI-1 1077:1082 arg1 structure 1051:1059 the structure 1047:1059 the structure of glycosylated AmyI-1 1047:1082 By contrast, regions around the N-linked glycosylation sites displayed lower conservation of amino acid residues, including Asn-263, Asn-265, Thr-307, Asn-342, Pro-373, and Ala-374 in AmyI-1, which are not conserved in barley α-amylases, suggesting that these residues may contribute to the construction of the structure of glycosylated AmyI-1. 25036124 3 16 theme 2.2-Å 440:444 arg1 resolution 446:455 2.2-Å resolution 440:455 2.2-Å resolution 440:455 In this study, we report the first crystal structure of AmyI-1 at 2.2-Å resolution. 25036124 2 17 theme plant 356:360 arg1 α-amylases 362:371 plant α-amylases 356:371 plant α-amylases 356:371 This enzyme is a glycoprotein with an N-glycosylated carbohydrate chain, a unique characteristic among plant α-amylases. 25036124 7 18 theme understanding 1126:1138 arg1 depths 1112:1117 the depths 1108:1117 the depths of our understanding of the biological functions of AmyI-1 1108:1176 These results increase the depths of our understanding of the biological functions of AmyI-1. 25036124 6 19 link N-linked 772:779 arg1 sites 795:799 the N-linked glycosylation sites 768:799 the N-linked glycosylation sites 768:799 By contrast, regions around the N-linked glycosylation sites displayed lower conservation of amino acid residues, including Asn-263, Asn-265, Thr-307, Asn-342, Pro-373, and Ala-374 in AmyI-1, which are not conserved in barley α-amylases, suggesting that these residues may contribute to the construction of the structure of glycosylated AmyI-1. 25036124 6 20 gly glycosylated 1064:1075 arg1 AmyI-1 1077:1082 glycosylated AmyI-1 1064:1082 glycosylated AmyI-1 1064:1082 By contrast, regions around the N-linked glycosylation sites displayed lower conservation of amino acid residues, including Asn-263, Asn-265, Thr-307, Asn-342, Pro-373, and Ala-374 in AmyI-1, which are not conserved in barley α-amylases, suggesting that these residues may contribute to the construction of the structure of glycosylated AmyI-1. 25036124 0 21 theme Crystal 0:6 arg1 structure 8:16 Crystal structure 0:16 Crystal structure of α-amylase from Oryza sativa: molecular insights into enzyme activity and thermostability. 0:109 Crystal structure of α-amylase from Oryza sativa: molecular insights into enzyme activity and thermostability. 25036124 1 22 theme growth 238:243 arg1 stages 245:250 various growth stages 230:250 various growth stages 230:250 AmyI-1 is an α-amylase from Oryza sativa (rice) and plays a crucial role in degrading starch in various tissues and at various growth stages. 25036124 0 23 theme α-amylase 21:29 arg1 structure 8:16 Crystal structure 0:16 Crystal structure of α-amylase from Oryza sativa: molecular insights into enzyme activity and thermostability. 0:109 Crystal structure of α-amylase from Oryza sativa: molecular insights into enzyme activity and thermostability. 25036124 3 24 from resolution 446:455 arg1 structure 417:425 the first crystal structure 399:425 the first crystal structure of AmyI-1 at 2.2-Å resolution 399:455 In this study, we report the first crystal structure of AmyI-1 at 2.2-Å resolution. 25036124 6 25 theme glycosylated 1064:1075 arg1 AmyI-1 1077:1082 glycosylated AmyI-1 1064:1082 glycosylated AmyI-1 1064:1082 By contrast, regions around the N-linked glycosylation sites displayed lower conservation of amino acid residues, including Asn-263, Asn-265, Thr-307, Asn-342, Pro-373, and Ala-374 in AmyI-1, which are not conserved in barley α-amylases, suggesting that these residues may contribute to the construction of the structure of glycosylated AmyI-1. 25036124 6 26 gly glycosylation 781:793 arg2 sites 795:799 the N-linked glycosylation sites 768:799 the N-linked glycosylation sites 768:799 By contrast, regions around the N-linked glycosylation sites displayed lower conservation of amino acid residues, including Asn-263, Asn-265, Thr-307, Asn-342, Pro-373, and Ala-374 in AmyI-1, which are not conserved in barley α-amylases, suggesting that these residues may contribute to the construction of the structure of glycosylated AmyI-1. 25036124 1 27 theme crucial 171:177 arg1 role 179:182 a crucial role 169:182 a crucial role 169:182 AmyI-1 is an α-amylase from Oryza sativa (rice) and plays a crucial role in degrading starch in various tissues and at various growth stages. 25036124 0 28 theme Oryza 36:40 arg1 sativa 42:47 Oryza sativa 36:47 Oryza sativa 36:47 Crystal structure of α-amylase from Oryza sativa: molecular insights into enzyme activity and thermostability. 25036124 5 29 theme carbohydrate-binding 675:694 arg1 sites 696:700 carbohydrate-binding sites 675:700 carbohydrate-binding sites between AmyI-1 and barley α-amylases 675:737 Structural superimposition indicated small variations in the catalytic domain and carbohydrate-binding sites between AmyI-1 and barley α-amylases. 25036124 3 30 theme first 403:407 arg1 structure 417:425 the first crystal structure 399:425 the first crystal structure of AmyI-1 at 2.2-Å resolution 399:455 In this study, we report the first crystal structure of AmyI-1 at 2.2-Å resolution. 25036124 6 31 theme residues 844:851 arg1 conservation 817:828 lower conservation 811:828 lower conservation of amino acid residues, including Asn-263, Asn-265, Thr-307, Asn-342, Pro-373, and Ala-374 in AmyI-1, which are not conserved in barley α-amylases 811:975 By contrast, regions around the N-linked glycosylation sites displayed lower conservation of amino acid residues, including Asn-263, Asn-265, Thr-307, Asn-342, Pro-373, and Ala-374 in AmyI-1, which are not conserved in barley α-amylases, suggesting that these residues may contribute to the construction of the structure of glycosylated AmyI-1. 25036124 3 32 theme crystal 409:415 arg1 structure 417:425 the first crystal structure 399:425 the first crystal structure of AmyI-1 at 2.2-Å resolution 399:455 In this study, we report the first crystal structure of AmyI-1 at 2.2-Å resolution. 25036124 2 33 gly N-glycosylated 291:304 arg1 characteristic 335:348 a unique characteristic 326:348 a unique characteristic among plant α-amylases 326:371 This enzyme is a glycoprotein with an N-glycosylated carbohydrate chain, a unique characteristic among plant α-amylases. 25036124 2 33 gly N-glycosylated 291:304 arg1 chain 319:323 an N-glycosylated carbohydrate chain 288:323 an N-glycosylated carbohydrate chain 288:323 This enzyme is a glycoprotein with an N-glycosylated carbohydrate chain, a unique characteristic among plant α-amylases. 25036124 0 34 theme molecular 50:58 arg1 insights 60:67 molecular insights 50:67 Crystal structure of α-amylase from Oryza sativa: molecular insights into enzyme activity and thermostability. 0:109 Crystal structure of α-amylase from Oryza sativa: molecular insights into enzyme activity and thermostability. 25036124 2 35 theme carbohydrate 306:317 arg1 characteristic 335:348 a unique characteristic 326:348 a unique characteristic among plant α-amylases 326:371 This enzyme is a glycoprotein with an N-glycosylated carbohydrate chain, a unique characteristic among plant α-amylases. 25036124 2 35 theme carbohydrate 306:317 arg1 chain 319:323 an N-glycosylated carbohydrate chain 288:323 an N-glycosylated carbohydrate chain 288:323 This enzyme is a glycoprotein with an N-glycosylated carbohydrate chain, a unique characteristic among plant α-amylases. 25036124 6 36 from Pro-373 900:906 arg1 AmyI-1 924:929 AmyI-1 924:929 AmyI-1 924:929 By contrast, regions around the N-linked glycosylation sites displayed lower conservation of amino acid residues, including Asn-263, Asn-265, Thr-307, Asn-342, Pro-373, and Ala-374 in AmyI-1, which are not conserved in barley α-amylases, suggesting that these residues may contribute to the construction of the structure of glycosylated AmyI-1. 25036124 6 37 theme amino 833:837 arg1 residues 844:851 amino acid residues 833:851 amino acid residues 833:851 By contrast, regions around the N-linked glycosylation sites displayed lower conservation of amino acid residues, including Asn-263, Asn-265, Thr-307, Asn-342, Pro-373, and Ala-374 in AmyI-1, which are not conserved in barley α-amylases, suggesting that these residues may contribute to the construction of the structure of glycosylated AmyI-1. 25036124 6 37 theme amino 833:837 arg1 Pro-373 900:906 Pro-373 900:906 Pro-373 900:906 By contrast, regions around the N-linked glycosylation sites displayed lower conservation of amino acid residues, including Asn-263, Asn-265, Thr-307, Asn-342, Pro-373, and Ala-374 in AmyI-1, which are not conserved in barley α-amylases, suggesting that these residues may contribute to the construction of the structure of glycosylated AmyI-1. 25036124 6 37 theme amino 833:837 arg1 Ala-374 913:919 Ala-374 913:919 Ala-374 913:919 By contrast, regions around the N-linked glycosylation sites displayed lower conservation of amino acid residues, including Asn-263, Asn-265, Thr-307, Asn-342, Pro-373, and Ala-374 in AmyI-1, which are not conserved in barley α-amylases, suggesting that these residues may contribute to the construction of the structure of glycosylated AmyI-1. 25036124 2 38 theme N-glycosylated 291:304 arg1 characteristic 335:348 a unique characteristic 326:348 a unique characteristic among plant α-amylases 326:371 This enzyme is a glycoprotein with an N-glycosylated carbohydrate chain, a unique characteristic among plant α-amylases. 25036124 2 38 theme N-glycosylated 291:304 arg1 chain 319:323 an N-glycosylated carbohydrate chain 288:323 an N-glycosylated carbohydrate chain 288:323 This enzyme is a glycoprotein with an N-glycosylated carbohydrate chain, a unique characteristic among plant α-amylases. 25036124 4 39 theme typical 486:492 arg1 well-conserved 518:531 well-conserved 518:531 well-conserved 518:531 The structure consists of a typical (β/α)8-barrel, which is well-conserved among most α-amylases in the glycoside hydrolase family-13. 25036124 4 39 theme typical 486:492 arg1 8-barrel 499:506 a typical (β/α)8-barrel 484:506 a typical (β/α)8-barrel 484:506 The structure consists of a typical (β/α)8-barrel, which is well-conserved among most α-amylases in the glycoside hydrolase family-13. 25036124 4 39 theme typical 486:492 arg1 β/α 495:497 β/α 495:497 β/α 495:497 The structure consists of a typical (β/α)8-barrel, which is well-conserved among most α-amylases in the glycoside hydrolase family-13. 25036124 3 40 theme AmyI-1 430:435 arg1 structure 417:425 the first crystal structure 399:425 the first crystal structure of AmyI-1 at 2.2-Å resolution 399:455 In this study, we report the first crystal structure of AmyI-1 at 2.2-Å resolution. 25036124 5 41 theme catalytic 654:662 arg1 domain 664:669 the catalytic domain 650:669 the catalytic domain 650:669 Structural superimposition indicated small variations in the catalytic domain and carbohydrate-binding sites between AmyI-1 and barley α-amylases. 25036124 6 42 theme structure 1051:1059 arg1 construction 1031:1042 the construction 1027:1042 the construction of the structure of glycosylated AmyI-1 1027:1082 By contrast, regions around the N-linked glycosylation sites displayed lower conservation of amino acid residues, including Asn-263, Asn-265, Thr-307, Asn-342, Pro-373, and Ala-374 in AmyI-1, which are not conserved in barley α-amylases, suggesting that these residues may contribute to the construction of the structure of glycosylated AmyI-1. 25036124 6 43 theme N-linked 772:779 arg1 sites 795:799 the N-linked glycosylation sites 768:799 the N-linked glycosylation sites 768:799 By contrast, regions around the N-linked glycosylation sites displayed lower conservation of amino acid residues, including Asn-263, Asn-265, Thr-307, Asn-342, Pro-373, and Ala-374 in AmyI-1, which are not conserved in barley α-amylases, suggesting that these residues may contribute to the construction of the structure of glycosylated AmyI-1. 25036124 4 44 theme most 539:542 arg1 α-amylases 544:553 most α-amylases 539:553 most α-amylases in the glycoside hydrolase family-13 539:590 The structure consists of a typical (β/α)8-barrel, which is well-conserved among most α-amylases in the glycoside hydrolase family-13. 25036124 6 45 theme lower 811:815 arg1 conservation 817:828 lower conservation 811:828 lower conservation of amino acid residues, including Asn-263, Asn-265, Thr-307, Asn-342, Pro-373, and Ala-374 in AmyI-1, which are not conserved in barley α-amylases 811:975 By contrast, regions around the N-linked glycosylation sites displayed lower conservation of amino acid residues, including Asn-263, Asn-265, Thr-307, Asn-342, Pro-373, and Ala-374 in AmyI-1, which are not conserved in barley α-amylases, suggesting that these residues may contribute to the construction of the structure of glycosylated AmyI-1. 25036124 0 46 dep structure 8:16 arg1 insights 60:67 molecular insights 50:67 Crystal structure of α-amylase from Oryza sativa: molecular insights into enzyme activity and thermostability. 0:109 Crystal structure of α-amylase from Oryza sativa: molecular insights into enzyme activity and thermostability. 25036124 2 47 theme unique 328:333 arg1 characteristic 335:348 a unique characteristic 326:348 a unique characteristic among plant α-amylases 326:371 This enzyme is a glycoprotein with an N-glycosylated carbohydrate chain, a unique characteristic among plant α-amylases. 25036124 2 47 theme unique 328:333 arg1 chain 319:323 an N-glycosylated carbohydrate chain 288:323 an N-glycosylated carbohydrate chain 288:323 This enzyme is a glycoprotein with an N-glycosylated carbohydrate chain, a unique characteristic among plant α-amylases. 25036124 5 48 from variations 636:645 arg1 domain 664:669 the catalytic domain 650:669 the catalytic domain 650:669 Structural superimposition indicated small variations in the catalytic domain and carbohydrate-binding sites between AmyI-1 and barley α-amylases. 25036124 5 48 from variations 636:645 arg1 sites 696:700 carbohydrate-binding sites 675:700 carbohydrate-binding sites between AmyI-1 and barley α-amylases 675:737 Structural superimposition indicated small variations in the catalytic domain and carbohydrate-binding sites between AmyI-1 and barley α-amylases. 25036124 2 49 gly glycoprotein 270:281 arg1 enzyme 258:263 This enzyme 253:263 This enzyme 253:263 This enzyme is a glycoprotein with an N-glycosylated carbohydrate chain, a unique characteristic among plant α-amylases. 25036124 2 49 gly glycoprotein 270:281 arg1 glycoprotein 270:281 a glycoprotein 268:281 a glycoprotein with an N-glycosylated carbohydrate chain, a unique characteristic among plant α-amylases 268:371 This enzyme is a glycoprotein with an N-glycosylated carbohydrate chain, a unique characteristic among plant α-amylases. 25036124 6 50 theme barley 959:964 arg1 α-amylases 966:975 barley α-amylases 959:975 barley α-amylases 959:975 By contrast, regions around the N-linked glycosylation sites displayed lower conservation of amino acid residues, including Asn-263, Asn-265, Thr-307, Asn-342, Pro-373, and Ala-374 in AmyI-1, which are not conserved in barley α-amylases, suggesting that these residues may contribute to the construction of the structure of glycosylated AmyI-1. 25036124 1 51 theme Oryza 139:143 arg1 rice 153:156 rice 153:156 rice 153:156 AmyI-1 is an α-amylase from Oryza sativa (rice) and plays a crucial role in degrading starch in various tissues and at various growth stages. 25036124 1 51 theme Oryza 139:143 arg1 sativa 145:150 Oryza sativa 139:150 Oryza sativa (rice) 139:157 AmyI-1 is an α-amylase from Oryza sativa (rice) and plays a crucial role in degrading starch in various tissues and at various growth stages. 25036124 1 52 theme various 207:213 arg1 tissues 215:221 various tissues 207:221 various tissues 207:221 AmyI-1 is an α-amylase from Oryza sativa (rice) and plays a crucial role in degrading starch in various tissues and at various growth stages. 29232605 0 0 theme ion 88:90 arg1 chromatography 101:114 ion exchange chromatography 88:114 ion exchange chromatography 88:114 Correlating charge heterogeneity data generated by agarose gel isoelectric focusing and ion exchange chromatography methods. 29232605 4 1 theme IEC 676:678 arg1 fractions 688:696 the IEC and IEF fractions 672:696 fractions 688:696 Tryptic peptide mapping and N- linked oligosaccharide profile analyses of the IEC and IEF fractions indicated a structural correlation between the charge variants separated by these two methods. 29232605 5 2 from variation 854:862 arg1 structure 894:902 the sialyated carbohydrate structure 867:902 the sialyated carbohydrate structure 867:902 The major sources of molecular heterogeneity were due to the variation in the sialyated carbohydrate structure and heavy chain C-terminal lysine truncation. 29232605 5 2 from variation 854:862 arg1 truncation 938:947 heavy chain C-terminal lysine truncation 908:947 heavy chain C-terminal lysine truncation 908:947 The major sources of molecular heterogeneity were due to the variation in the sialyated carbohydrate structure and heavy chain C-terminal lysine truncation. 29232605 4 3 theme IEF 684:686 arg1 fractions 688:696 the IEC and IEF fractions 672:696 fractions 688:696 Tryptic peptide mapping and N- linked oligosaccharide profile analyses of the IEC and IEF fractions indicated a structural correlation between the charge variants separated by these two methods. 29232605 6 4 theme heterogeneity 998:1010 arg1 profiles 1012:1019 the charge heterogeneity profiles 987:1019 the charge heterogeneity profiles of the monoclonal antibody stored at elevated temperatures by the IEC and IEF methods 987:1105 By monitoring the rates of change in the charge heterogeneity profiles of the monoclonal antibody stored at elevated temperatures by the IEC and IEF methods, a positive correlation between the two methods was established. 29232605 5 5 theme chain 914:918 arg1 truncation 938:947 heavy chain C-terminal lysine truncation 908:947 heavy chain C-terminal lysine truncation 908:947 The major sources of molecular heterogeneity were due to the variation in the sialyated carbohydrate structure and heavy chain C-terminal lysine truncation. 29232605 6 6 from profiles 1012:1019 arg1 rates 968:972 the rates 964:972 the rates of change in the charge heterogeneity profiles of the monoclonal antibody stored at elevated temperatures by the IEC and IEF methods 964:1105 By monitoring the rates of change in the charge heterogeneity profiles of the monoclonal antibody stored at elevated temperatures by the IEC and IEF methods, a positive correlation between the two methods was established. 29232605 7 7 theme precise 1238:1244 arg1 method 1250:1255 the more precise IEC method 1229:1255 the more precise IEC method 1229:1255 This approach enabled replacement of the IEF method with the more precise IEC method. 29232605 6 8 theme charge 991:996 arg1 profiles 1012:1019 the charge heterogeneity profiles 987:1019 the charge heterogeneity profiles of the monoclonal antibody stored at elevated temperatures by the IEC and IEF methods 987:1105 By monitoring the rates of change in the charge heterogeneity profiles of the monoclonal antibody stored at elevated temperatures by the IEC and IEF methods, a positive correlation between the two methods was established. 29232605 6 9 theme IEF 1095:1097 arg1 methods 1099:1105 the IEC and IEF methods 1083:1105 methods 1099:1105 By monitoring the rates of change in the charge heterogeneity profiles of the monoclonal antibody stored at elevated temperatures by the IEC and IEF methods, a positive correlation between the two methods was established. 29232605 1 10 dep focusing 140:147 arg1 isoelectric 128:138 isoelectric 128:138 isoelectric 128:138 An isoelectric focusing method (IEF) has been used to assess the charge heterogeneity profile of a monoclonal antibody during the early stages of product development. 29232605 1 11 theme early 255:259 arg1 stages 261:266 the early stages 251:266 the early stages of product development 251:289 An isoelectric focusing method (IEF) has been used to assess the charge heterogeneity profile of a monoclonal antibody during the early stages of product development. 29232605 0 12 theme exchange 92:99 arg1 chromatography 101:114 ion exchange chromatography 88:114 ion exchange chromatography 88:114 Correlating charge heterogeneity data generated by agarose gel isoelectric focusing and ion exchange chromatography methods. 29232605 4 13 theme structural 710:719 arg1 correlation 721:731 a structural correlation 708:731 a structural correlation between the charge variants separated by these two methods 708:790 Tryptic peptide mapping and N- linked oligosaccharide profile analyses of the IEC and IEF fractions indicated a structural correlation between the charge variants separated by these two methods. 29232605 3 14 dep methods 543:549 arg1 IEC 552:554 IEC 552:554 IEC 552:554 Charge variants resolved by both methods (IEC and IEF) were purified and characterized. 29232605 3 14 dep methods 543:549 arg1 methods 543:549 both methods 538:549 both methods (IEC and IEF) 538:563 Charge variants resolved by both methods (IEC and IEF) were purified and characterized. 29232605 3 14 dep methods 543:549 arg1 IEF 560:562 IEF 560:562 IEF 560:562 Charge variants resolved by both methods (IEC and IEF) were purified and characterized. 29232605 2 15 used used 430:433 arg2 method 359:364 A more precise and sensitive ion exchange chromatography (IEC/CEX) method 292:364 A more precise and sensitive ion exchange chromatography (IEC/CEX) method 292:364 A more precise and sensitive ion exchange chromatography (IEC/CEX) method was developed and implemented as development progressed and was used concurrently with IEF for lot release and to monitor charge heterogeneity. 29232605 2 15 used used 430:433 arg2 progressed 411:420 development progressed 399:420 development progressed 399:420 A more precise and sensitive ion exchange chromatography (IEC/CEX) method was developed and implemented as development progressed and was used concurrently with IEF for lot release and to monitor charge heterogeneity. 29232605 5 16 theme major 797:801 arg1 due 843:845 due 843:845 due 843:845 The major sources of molecular heterogeneity were due to the variation in the sialyated carbohydrate structure and heavy chain C-terminal lysine truncation. 29232605 5 16 theme major 797:801 arg1 sources 803:809 The major sources 793:809 The major sources of molecular heterogeneity 793:836 The major sources of molecular heterogeneity were due to the variation in the sialyated carbohydrate structure and heavy chain C-terminal lysine truncation. 29232605 5 17 theme C-terminal 920:929 arg1 truncation 938:947 heavy chain C-terminal lysine truncation 908:947 heavy chain C-terminal lysine truncation 908:947 The major sources of molecular heterogeneity were due to the variation in the sialyated carbohydrate structure and heavy chain C-terminal lysine truncation. 29232605 4 18 theme profile 652:658 arg1 analyses 660:667 linked oligosaccharide profile analyses 629:667 linked oligosaccharide profile analyses 629:667 Tryptic peptide mapping and N- linked oligosaccharide profile analyses of the IEC and IEF fractions indicated a structural correlation between the charge variants separated by these two methods. 29232605 6 19 theme positive 1110:1117 arg1 correlation 1119:1129 a positive correlation 1108:1129 a positive correlation between the two methods 1108:1153 By monitoring the rates of change in the charge heterogeneity profiles of the monoclonal antibody stored at elevated temperatures by the IEC and IEF methods, a positive correlation between the two methods was established. 29232605 4 20 theme oligosaccharide 636:650 arg1 analyses 660:667 linked oligosaccharide profile analyses 629:667 linked oligosaccharide profile analyses 629:667 Tryptic peptide mapping and N- linked oligosaccharide profile analyses of the IEC and IEF fractions indicated a structural correlation between the charge variants separated by these two methods. 29232605 0 21 theme charge 12:17 arg1 data 33:36 charge heterogeneity data 12:36 charge heterogeneity data generated by agarose gel isoelectric focusing and ion exchange chromatography methods 12:122 Correlating charge heterogeneity data generated by agarose gel isoelectric focusing and ion exchange chromatography methods. 29232605 7 22 theme method 1217:1222 arg1 replacement 1194:1204 replacement 1194:1204 replacement of the IEF method with the more precise IEC method 1194:1255 This approach enabled replacement of the IEF method with the more precise IEC method. 29232605 6 23 theme IEC 1087:1089 arg1 methods 1099:1105 the IEC and IEF methods 1083:1105 methods 1099:1105 By monitoring the rates of change in the charge heterogeneity profiles of the monoclonal antibody stored at elevated temperatures by the IEC and IEF methods, a positive correlation between the two methods was established. 29232605 7 24 theme IEC 1246:1248 arg1 method 1250:1255 the more precise IEC method 1229:1255 the more precise IEC method 1229:1255 This approach enabled replacement of the IEF method with the more precise IEC method. 29232605 4 25 theme linked 629:634 arg1 analyses 660:667 linked oligosaccharide profile analyses 629:667 linked oligosaccharide profile analyses 629:667 Tryptic peptide mapping and N- linked oligosaccharide profile analyses of the IEC and IEF fractions indicated a structural correlation between the charge variants separated by these two methods. 29232605 6 26 theme change 977:982 arg1 rates 968:972 the rates 964:972 the rates of change in the charge heterogeneity profiles of the monoclonal antibody stored at elevated temperatures by the IEC and IEF methods 964:1105 By monitoring the rates of change in the charge heterogeneity profiles of the monoclonal antibody stored at elevated temperatures by the IEC and IEF methods, a positive correlation between the two methods was established. 29232605 2 27 theme precise 299:305 arg1 IEC/CEX 350:356 IEC/CEX 350:356 IEC/CEX 350:356 A more precise and sensitive ion exchange chromatography (IEC/CEX) method was developed and implemented as development progressed and was used concurrently with IEF for lot release and to monitor charge heterogeneity. 29232605 2 27 theme precise 299:305 arg1 chromatography 334:347 A more precise and sensitive ion exchange chromatography 292:347 A more precise and sensitive ion exchange chromatography (IEC/CEX) method 292:364 A more precise and sensitive ion exchange chromatography (IEC/CEX) method was developed and implemented as development progressed and was used concurrently with IEF for lot release and to monitor charge heterogeneity. 29232605 1 28 theme product 271:277 arg1 development 279:289 product development 271:289 product development 271:289 An isoelectric focusing method (IEF) has been used to assess the charge heterogeneity profile of a monoclonal antibody during the early stages of product development. 29232605 6 29 from rates 968:972 arg1 profiles 1012:1019 the charge heterogeneity profiles 987:1019 the charge heterogeneity profiles of the monoclonal antibody stored at elevated temperatures by the IEC and IEF methods 987:1105 By monitoring the rates of change in the charge heterogeneity profiles of the monoclonal antibody stored at elevated temperatures by the IEC and IEF methods, a positive correlation between the two methods was established. 29232605 5 30 theme lysine 931:936 arg1 truncation 938:947 heavy chain C-terminal lysine truncation 908:947 heavy chain C-terminal lysine truncation 908:947 The major sources of molecular heterogeneity were due to the variation in the sialyated carbohydrate structure and heavy chain C-terminal lysine truncation. 29232605 4 31 theme charge 745:750 arg1 variants 752:759 the charge variants 741:759 the charge variants separated by these two methods 741:790 Tryptic peptide mapping and N- linked oligosaccharide profile analyses of the IEC and IEF fractions indicated a structural correlation between the charge variants separated by these two methods. 29232605 5 32 theme heterogeneity 824:836 arg1 due 843:845 due 843:845 due 843:845 The major sources of molecular heterogeneity were due to the variation in the sialyated carbohydrate structure and heavy chain C-terminal lysine truncation. 29232605 5 32 theme heterogeneity 824:836 arg1 sources 803:809 The major sources 793:809 The major sources of molecular heterogeneity 793:836 The major sources of molecular heterogeneity were due to the variation in the sialyated carbohydrate structure and heavy chain C-terminal lysine truncation. 29232605 0 33 theme heterogeneity 19:31 arg1 data 33:36 charge heterogeneity data 12:36 charge heterogeneity data generated by agarose gel isoelectric focusing and ion exchange chromatography methods 12:122 Correlating charge heterogeneity data generated by agarose gel isoelectric focusing and ion exchange chromatography methods. 29232605 1 34 theme development 279:289 arg1 stages 261:266 the early stages 251:266 the early stages of product development 251:289 An isoelectric focusing method (IEF) has been used to assess the charge heterogeneity profile of a monoclonal antibody during the early stages of product development. 29232605 0 35 dep isoelectric 63:73 arg1 methods 116:122 methods 116:122 methods 116:122 Correlating charge heterogeneity data generated by agarose gel isoelectric focusing and ion exchange chromatography methods. 29232605 1 36 theme charge 190:195 arg1 profile 211:217 the charge heterogeneity profile 186:217 the charge heterogeneity profile of a monoclonal antibody 186:242 An isoelectric focusing method (IEF) has been used to assess the charge heterogeneity profile of a monoclonal antibody during the early stages of product development. 29232605 4 37 theme fractions 688:696 arg1 N- 626:627 N- 626:627 N- 626:627 Tryptic peptide mapping and N- linked oligosaccharide profile analyses of the IEC and IEF fractions indicated a structural correlation between the charge variants separated by these two methods. 29232605 4 37 theme fractions 688:696 arg1 mapping 614:620 Tryptic peptide mapping 598:620 Tryptic peptide mapping 598:620 Tryptic peptide mapping and N- linked oligosaccharide profile analyses of the IEC and IEF fractions indicated a structural correlation between the charge variants separated by these two methods. 29232605 6 38 from change 977:982 arg1 profiles 1012:1019 the charge heterogeneity profiles 987:1019 the charge heterogeneity profiles of the monoclonal antibody stored at elevated temperatures by the IEC and IEF methods 987:1105 By monitoring the rates of change in the charge heterogeneity profiles of the monoclonal antibody stored at elevated temperatures by the IEC and IEF methods, a positive correlation between the two methods was established. 29232605 1 39 theme heterogeneity 197:209 arg1 profile 211:217 the charge heterogeneity profile 186:217 the charge heterogeneity profile of a monoclonal antibody 186:242 An isoelectric focusing method (IEF) has been used to assess the charge heterogeneity profile of a monoclonal antibody during the early stages of product development. 29232605 2 40 theme development 399:409 arg1 progressed 411:420 development progressed 399:420 development progressed 399:420 A more precise and sensitive ion exchange chromatography (IEC/CEX) method was developed and implemented as development progressed and was used concurrently with IEF for lot release and to monitor charge heterogeneity. 29232605 2 40 theme development 399:409 arg1 method 359:364 A more precise and sensitive ion exchange chromatography (IEC/CEX) method 292:364 A more precise and sensitive ion exchange chromatography (IEC/CEX) method 292:364 A more precise and sensitive ion exchange chromatography (IEC/CEX) method was developed and implemented as development progressed and was used concurrently with IEF for lot release and to monitor charge heterogeneity. 29232605 2 41 theme lot 461:463 arg1 release 465:471 lot release 461:471 lot release 461:471 A more precise and sensitive ion exchange chromatography (IEC/CEX) method was developed and implemented as development progressed and was used concurrently with IEF for lot release and to monitor charge heterogeneity. 29232605 4 42 theme peptide 606:612 arg1 mapping 614:620 Tryptic peptide mapping 598:620 Tryptic peptide mapping 598:620 Tryptic peptide mapping and N- linked oligosaccharide profile analyses of the IEC and IEF fractions indicated a structural correlation between the charge variants separated by these two methods. 29232605 6 43 theme antibody 1039:1046 arg1 profiles 1012:1019 the charge heterogeneity profiles 987:1019 the charge heterogeneity profiles of the monoclonal antibody stored at elevated temperatures by the IEC and IEF methods 987:1105 By monitoring the rates of change in the charge heterogeneity profiles of the monoclonal antibody stored at elevated temperatures by the IEC and IEF methods, a positive correlation between the two methods was established. 29232605 5 44 theme sialyated 871:879 arg1 structure 894:902 the sialyated carbohydrate structure 867:902 the sialyated carbohydrate structure 867:902 The major sources of molecular heterogeneity were due to the variation in the sialyated carbohydrate structure and heavy chain C-terminal lysine truncation. 29232605 2 45 theme chromatography 334:347 arg1 progressed 411:420 development progressed 399:420 development progressed 399:420 A more precise and sensitive ion exchange chromatography (IEC/CEX) method was developed and implemented as development progressed and was used concurrently with IEF for lot release and to monitor charge heterogeneity. 29232605 2 45 theme chromatography 334:347 arg1 method 359:364 A more precise and sensitive ion exchange chromatography (IEC/CEX) method 292:364 A more precise and sensitive ion exchange chromatography (IEC/CEX) method 292:364 A more precise and sensitive ion exchange chromatography (IEC/CEX) method was developed and implemented as development progressed and was used concurrently with IEF for lot release and to monitor charge heterogeneity. 29232605 4 46 dep mapping 614:620 arg1 analyses 660:667 linked oligosaccharide profile analyses 629:667 linked oligosaccharide profile analyses 629:667 Tryptic peptide mapping and N- linked oligosaccharide profile analyses of the IEC and IEF fractions indicated a structural correlation between the charge variants separated by these two methods. 29232605 2 47 theme exchange 325:332 arg1 IEC/CEX 350:356 IEC/CEX 350:356 IEC/CEX 350:356 A more precise and sensitive ion exchange chromatography (IEC/CEX) method was developed and implemented as development progressed and was used concurrently with IEF for lot release and to monitor charge heterogeneity. 29232605 2 47 theme exchange 325:332 arg1 chromatography 334:347 A more precise and sensitive ion exchange chromatography 292:347 A more precise and sensitive ion exchange chromatography (IEC/CEX) method 292:364 A more precise and sensitive ion exchange chromatography (IEC/CEX) method was developed and implemented as development progressed and was used concurrently with IEF for lot release and to monitor charge heterogeneity. 29232605 4 48 link linked 629:634 arg1 analyses 660:667 linked oligosaccharide profile analyses 629:667 linked oligosaccharide profile analyses 629:667 Tryptic peptide mapping and N- linked oligosaccharide profile analyses of the IEC and IEF fractions indicated a structural correlation between the charge variants separated by these two methods. 29232605 7 49 with replacement 1194:1204 arg1 method 1250:1255 the more precise IEC method 1229:1255 the more precise IEC method 1229:1255 This approach enabled replacement of the IEF method with the more precise IEC method. 29232605 1 50 theme focusing 140:147 arg1 IEF 157:159 IEF 157:159 IEF 157:159 An isoelectric focusing method (IEF) has been used to assess the charge heterogeneity profile of a monoclonal antibody during the early stages of product development. 29232605 1 50 theme focusing 140:147 arg1 method 149:154 An isoelectric focusing method 125:154 An isoelectric focusing method (IEF) 125:160 An isoelectric focusing method (IEF) has been used to assess the charge heterogeneity profile of a monoclonal antibody during the early stages of product development. 29232605 6 51 theme monoclonal 1028:1037 arg1 antibody 1039:1046 the monoclonal antibody 1024:1046 the monoclonal antibody stored at elevated temperatures by the IEC and IEF methods 1024:1105 By monitoring the rates of change in the charge heterogeneity profiles of the monoclonal antibody stored at elevated temperatures by the IEC and IEF methods, a positive correlation between the two methods was established. 29232605 7 52 theme IEF 1213:1215 arg1 method 1217:1222 the IEF method 1209:1222 the IEF method 1209:1222 This approach enabled replacement of the IEF method with the more precise IEC method. 29232605 5 53 theme heavy 908:912 arg1 truncation 938:947 heavy chain C-terminal lysine truncation 908:947 heavy chain C-terminal lysine truncation 908:947 The major sources of molecular heterogeneity were due to the variation in the sialyated carbohydrate structure and heavy chain C-terminal lysine truncation. 29232605 5 54 theme molecular 814:822 arg1 heterogeneity 824:836 molecular heterogeneity 814:836 molecular heterogeneity 814:836 The major sources of molecular heterogeneity were due to the variation in the sialyated carbohydrate structure and heavy chain C-terminal lysine truncation. 29232605 2 55 theme sensitive 311:319 arg1 IEC/CEX 350:356 IEC/CEX 350:356 IEC/CEX 350:356 A more precise and sensitive ion exchange chromatography (IEC/CEX) method was developed and implemented as development progressed and was used concurrently with IEF for lot release and to monitor charge heterogeneity. 29232605 2 55 theme sensitive 311:319 arg1 chromatography 334:347 A more precise and sensitive ion exchange chromatography 292:347 A more precise and sensitive ion exchange chromatography (IEC/CEX) method 292:364 A more precise and sensitive ion exchange chromatography (IEC/CEX) method was developed and implemented as development progressed and was used concurrently with IEF for lot release and to monitor charge heterogeneity. 29232605 2 56 theme ion 321:323 arg1 IEC/CEX 350:356 IEC/CEX 350:356 IEC/CEX 350:356 A more precise and sensitive ion exchange chromatography (IEC/CEX) method was developed and implemented as development progressed and was used concurrently with IEF for lot release and to monitor charge heterogeneity. 29232605 2 56 theme ion 321:323 arg1 chromatography 334:347 A more precise and sensitive ion exchange chromatography 292:347 A more precise and sensitive ion exchange chromatography (IEC/CEX) method 292:364 A more precise and sensitive ion exchange chromatography (IEC/CEX) method was developed and implemented as development progressed and was used concurrently with IEF for lot release and to monitor charge heterogeneity. 29232605 2 57 theme charge 488:493 arg1 heterogeneity 495:507 charge heterogeneity 488:507 charge heterogeneity 488:507 A more precise and sensitive ion exchange chromatography (IEC/CEX) method was developed and implemented as development progressed and was used concurrently with IEF for lot release and to monitor charge heterogeneity. 29232605 1 58 used used 171:174 arg2 IEF 157:159 IEF 157:159 IEF 157:159 An isoelectric focusing method (IEF) has been used to assess the charge heterogeneity profile of a monoclonal antibody during the early stages of product development. 29232605 1 58 used used 171:174 arg2 method 149:154 An isoelectric focusing method 125:154 An isoelectric focusing method (IEF) 125:160 An isoelectric focusing method (IEF) has been used to assess the charge heterogeneity profile of a monoclonal antibody during the early stages of product development. 29232605 6 59 theme elevated 1058:1065 arg1 temperatures 1067:1078 elevated temperatures 1058:1078 elevated temperatures 1058:1078 By monitoring the rates of change in the charge heterogeneity profiles of the monoclonal antibody stored at elevated temperatures by the IEC and IEF methods, a positive correlation between the two methods was established. 29232605 3 60 theme Charge 510:515 arg1 variants 517:524 Charge variants 510:524 Charge variants resolved by both methods (IEC and IEF) 510:563 Charge variants resolved by both methods (IEC and IEF) were purified and characterized. 29232605 1 61 theme monoclonal 224:233 arg1 antibody 235:242 a monoclonal antibody 222:242 a monoclonal antibody 222:242 An isoelectric focusing method (IEF) has been used to assess the charge heterogeneity profile of a monoclonal antibody during the early stages of product development. 29232605 4 62 theme Tryptic 598:604 arg1 mapping 614:620 Tryptic peptide mapping 598:620 Tryptic peptide mapping 598:620 Tryptic peptide mapping and N- linked oligosaccharide profile analyses of the IEC and IEF fractions indicated a structural correlation between the charge variants separated by these two methods. 29232605 5 63 theme carbohydrate 881:892 arg1 structure 894:902 the sialyated carbohydrate structure 867:902 the sialyated carbohydrate structure 867:902 The major sources of molecular heterogeneity were due to the variation in the sialyated carbohydrate structure and heavy chain C-terminal lysine truncation. 29232605 1 64 theme antibody 235:242 arg1 profile 211:217 the charge heterogeneity profile 186:217 the charge heterogeneity profile of a monoclonal antibody 186:242 An isoelectric focusing method (IEF) has been used to assess the charge heterogeneity profile of a monoclonal antibody during the early stages of product development. 28834292 6 0 theme B 983:983 arg1 cells 990:994 B or T cells 983:994 B or T cells within the Cell Surface Protein Atlas 983:1032 Altogether, 404 cell surface N-glycoproteins were identified as markers for specific cell types involved in lymphocytic malignancies, including 82 N-glycoproteins that had not been previously been described for B or T cells within the Cell Surface Protein Atlas. 28834292 5 1 theme approach 654:661 arg1 use 623:625 the use 619:625 the use of an antibody independent approach known as Cell Surface Capture Technology 619:702 Specifically, this manuscript details the use of an antibody independent approach known as Cell Surface Capture Technology, to assess the N-glycoproteome of four human lymphocyte cell lines. 28834292 8 2 theme lymphoma 1361:1368 arg1 treatment 1335:1343 treatment 1335:1343 treatment 1335:1343 Undoubtedly, the characterization of the cell surface proteome of lymphoid malignancies is a first step toward improving personalized diagnosis and treatment of leukemia and lymphoma. 28834292 8 2 theme lymphoma 1361:1368 arg1 diagnosis 1321:1329 personalized diagnosis 1308:1329 personalized diagnosis 1308:1329 Undoubtedly, the characterization of the cell surface proteome of lymphoid malignancies is a first step toward improving personalized diagnosis and treatment of leukemia and lymphoma. 28834292 5 3 theme Surface 677:683 arg1 Technology 693:702 Cell Surface Capture Technology 672:702 Cell Surface Capture Technology 672:702 Specifically, this manuscript details the use of an antibody independent approach known as Cell Surface Capture Technology, to assess the N-glycoproteome of four human lymphocyte cell lines. 28834292 6 4 theme Cell 1007:1010 arg1 Atlas 1028:1032 the Cell Surface Protein Atlas 1003:1032 the Cell Surface Protein Atlas 1003:1032 Altogether, 404 cell surface N-glycoproteins were identified as markers for specific cell types involved in lymphocytic malignancies, including 82 N-glycoproteins that had not been previously been described for B or T cells within the Cell Surface Protein Atlas. 28834292 0 5 theme Lymphocytes 70:80 arg1 Typing 54:59 Typing 54:59 Typing of Human Lymphocytes 54:80 Cell Surface Proteomics of N-Linked Glycoproteins for Typing of Human Lymphocytes. 28834292 7 6 theme label-free 1097:1106 arg1 quantitation 1108:1119 label-free quantitation 1097:1119 label-free quantitation 1097:1119 Comparative analysis, hierarchical clustering techniques, and label-free quantitation were used to reveal proteins most informative for each cell type. 28834292 1 7 theme adaptive 153:160 arg1 immunity 162:169 adaptive immunity 153:169 adaptive immunity 153:169 Lymphocytes are immune cells that are critical for the maintenance of adaptive immunity. 28834292 6 8 gly N-glycoproteins 919:933 arg1 N-glycoproteins 919:933 82 N-glycoproteins 916:933 82 N-glycoproteins that had not been previously been described for B or T cells within the Cell Surface Protein Atlas 916:1032 Altogether, 404 cell surface N-glycoproteins were identified as markers for specific cell types involved in lymphocytic malignancies, including 82 N-glycoproteins that had not been previously been described for B or T cells within the Cell Surface Protein Atlas. 28834292 6 9 theme cell 788:791 arg1 markers 836:842 markers 836:842 markers for specific cell types involved in lymphocytic malignancies, including 82 N-glycoproteins that had not been previously been described for B or T cells within the Cell Surface Protein Atlas 836:1032 Altogether, 404 cell surface N-glycoproteins were identified as markers for specific cell types involved in lymphocytic malignancies, including 82 N-glycoproteins that had not been previously been described for B or T cells within the Cell Surface Protein Atlas. 28834292 6 9 theme cell 788:791 arg1 N-glycoproteins 801:815 404 cell surface N-glycoproteins 784:815 404 cell surface N-glycoproteins 784:815 Altogether, 404 cell surface N-glycoproteins were identified as markers for specific cell types involved in lymphocytic malignancies, including 82 N-glycoproteins that had not been previously been described for B or T cells within the Cell Surface Protein Atlas. 28834292 3 10 theme precise 351:357 arg1 method 359:364 a precise method 349:364 a precise method of cell categorization 349:387 Therefore, it is imperative a precise method of cell categorization is utilized to detect differences in distinct disease states present in patients. 28834292 5 11 theme Cell 672:675 arg1 Technology 693:702 Cell Surface Capture Technology 672:702 Cell Surface Capture Technology 672:702 Specifically, this manuscript details the use of an antibody independent approach known as Cell Surface Capture Technology, to assess the N-glycoproteome of four human lymphocyte cell lines. 28834292 3 12 attach present 450:456 arg2 states 443:448 distinct disease states 426:448 distinct disease states present in patients 426:468 Therefore, it is imperative a precise method of cell categorization is utilized to detect differences in distinct disease states present in patients. 28834292 3 12 attach present 450:456 arg1 patients 461:468 patients 461:468 patients 461:468 Therefore, it is imperative a precise method of cell categorization is utilized to detect differences in distinct disease states present in patients. 28834292 2 13 theme specific 281:288 arg1 forms 290:294 specific forms 281:294 specific forms of leukemia or lymphoma 281:318 Differentiation of lymphoid progenitors yields B-, T-, and NK-cell subtypes that individually correlate with specific forms of leukemia or lymphoma. 28834292 5 14 theme human 743:747 arg1 lines 765:769 four human lymphocyte cell lines 738:769 four human lymphocyte cell lines 738:769 Specifically, this manuscript details the use of an antibody independent approach known as Cell Surface Capture Technology, to assess the N-glycoproteome of four human lymphocyte cell lines. 28834292 1 15 theme immunity 162:169 arg1 maintenance 138:148 the maintenance 134:148 the maintenance of adaptive immunity 134:169 Lymphocytes are immune cells that are critical for the maintenance of adaptive immunity. 28834292 5 16 theme lymphocyte 749:758 arg1 lines 765:769 four human lymphocyte cell lines 738:769 four human lymphocyte cell lines 738:769 Specifically, this manuscript details the use of an antibody independent approach known as Cell Surface Capture Technology, to assess the N-glycoproteome of four human lymphocyte cell lines. 28834292 8 17 theme surface 1233:1239 arg1 proteome 1241:1248 the cell surface proteome 1224:1248 the cell surface proteome of lymphoid malignancies 1224:1273 Undoubtedly, the characterization of the cell surface proteome of lymphoid malignancies is a first step toward improving personalized diagnosis and treatment of leukemia and lymphoma. 28834292 6 18 theme surface 793:799 arg1 markers 836:842 markers 836:842 markers for specific cell types involved in lymphocytic malignancies, including 82 N-glycoproteins that had not been previously been described for B or T cells within the Cell Surface Protein Atlas 836:1032 Altogether, 404 cell surface N-glycoproteins were identified as markers for specific cell types involved in lymphocytic malignancies, including 82 N-glycoproteins that had not been previously been described for B or T cells within the Cell Surface Protein Atlas. 28834292 6 18 theme surface 793:799 arg1 N-glycoproteins 801:815 404 cell surface N-glycoproteins 784:815 404 cell surface N-glycoproteins 784:815 Altogether, 404 cell surface N-glycoproteins were identified as markers for specific cell types involved in lymphocytic malignancies, including 82 N-glycoproteins that had not been previously been described for B or T cells within the Cell Surface Protein Atlas. 28834292 0 19 theme Cell 0:3 arg1 Proteomics 13:22 Cell Surface Proteomics 0:22 Cell Surface Proteomics of N-Linked Glycoproteins for Typing of Human Lymphocytes. 0:81 Cell Surface Proteomics of N-Linked Glycoproteins for Typing of Human Lymphocytes. 28834292 6 20 gly N-glycoproteins 801:815 arg1 markers 836:842 markers 836:842 markers for specific cell types involved in lymphocytic malignancies, including 82 N-glycoproteins that had not been previously been described for B or T cells within the Cell Surface Protein Atlas 836:1032 Altogether, 404 cell surface N-glycoproteins were identified as markers for specific cell types involved in lymphocytic malignancies, including 82 N-glycoproteins that had not been previously been described for B or T cells within the Cell Surface Protein Atlas. 28834292 6 20 gly N-glycoproteins 801:815 arg1 N-glycoproteins 801:815 404 cell surface N-glycoproteins 784:815 404 cell surface N-glycoproteins 784:815 Altogether, 404 cell surface N-glycoproteins were identified as markers for specific cell types involved in lymphocytic malignancies, including 82 N-glycoproteins that had not been previously been described for B or T cells within the Cell Surface Protein Atlas. 28834292 3 21 theme disease 435:441 arg1 states 443:448 distinct disease states 426:448 distinct disease states present in patients 426:468 Therefore, it is imperative a precise method of cell categorization is utilized to detect differences in distinct disease states present in patients. 28834292 0 22 theme Surface 5:11 arg1 Proteomics 13:22 Cell Surface Proteomics 0:22 Cell Surface Proteomics of N-Linked Glycoproteins for Typing of Human Lymphocytes. 0:81 Cell Surface Proteomics of N-Linked Glycoproteins for Typing of Human Lymphocytes. 28834292 4 23 theme viable 475:480 arg1 means 482:486 One viable means 471:486 One viable means of classification 471:504 One viable means of classification involves evaluation of the cell surface proteome of lymphoid malignancies. 28834292 5 24 theme antibody 633:640 arg1 approach 654:661 an antibody independent approach 630:661 an antibody independent approach known as Cell Surface Capture Technology 630:702 Specifically, this manuscript details the use of an antibody independent approach known as Cell Surface Capture Technology, to assess the N-glycoproteome of four human lymphocyte cell lines. 28834292 5 25 theme cell 760:763 arg1 lines 765:769 four human lymphocyte cell lines 738:769 four human lymphocyte cell lines 738:769 Specifically, this manuscript details the use of an antibody independent approach known as Cell Surface Capture Technology, to assess the N-glycoproteome of four human lymphocyte cell lines. 28834292 2 26 theme lymphoma 311:318 arg1 forms 290:294 specific forms 281:294 specific forms of leukemia or lymphoma 281:318 Differentiation of lymphoid progenitors yields B-, T-, and NK-cell subtypes that individually correlate with specific forms of leukemia or lymphoma. 28834292 7 27 theme hierarchical 1057:1068 arg1 techniques 1081:1090 hierarchical clustering techniques 1057:1090 hierarchical clustering techniques 1057:1090 Comparative analysis, hierarchical clustering techniques, and label-free quantitation were used to reveal proteins most informative for each cell type. 28834292 3 28 theme categorization 374:387 arg1 method 359:364 a precise method 349:364 a precise method of cell categorization 349:387 Therefore, it is imperative a precise method of cell categorization is utilized to detect differences in distinct disease states present in patients. 28834292 6 29 theme T 988:988 arg1 cells 990:994 B or T cells 983:994 B or T cells within the Cell Surface Protein Atlas 983:1032 Altogether, 404 cell surface N-glycoproteins were identified as markers for specific cell types involved in lymphocytic malignancies, including 82 N-glycoproteins that had not been previously been described for B or T cells within the Cell Surface Protein Atlas. 28834292 5 30 theme independent 642:652 arg1 approach 654:661 an antibody independent approach 630:661 an antibody independent approach known as Cell Surface Capture Technology 630:702 Specifically, this manuscript details the use of an antibody independent approach known as Cell Surface Capture Technology, to assess the N-glycoproteome of four human lymphocyte cell lines. 28834292 6 31 theme cell 857:860 arg1 types 862:866 specific cell types 848:866 specific cell types involved in lymphocytic malignancies, including 82 N-glycoproteins that had not been previously been described for B or T cells within the Cell Surface Protein Atlas 848:1032 Altogether, 404 cell surface N-glycoproteins were identified as markers for specific cell types involved in lymphocytic malignancies, including 82 N-glycoproteins that had not been previously been described for B or T cells within the Cell Surface Protein Atlas. 28834292 4 32 theme proteome 546:553 arg1 evaluation 515:524 evaluation 515:524 evaluation of the cell surface proteome of lymphoid malignancies 515:578 One viable means of classification involves evaluation of the cell surface proteome of lymphoid malignancies. 28834292 2 33 theme leukemia 299:306 arg1 forms 290:294 specific forms 281:294 specific forms of leukemia or lymphoma 281:318 Differentiation of lymphoid progenitors yields B-, T-, and NK-cell subtypes that individually correlate with specific forms of leukemia or lymphoma. 28834292 4 34 theme malignancies 567:578 arg1 proteome 546:553 the cell surface proteome 529:553 the cell surface proteome of lymphoid malignancies 529:578 One viable means of classification involves evaluation of the cell surface proteome of lymphoid malignancies. 28834292 6 35 theme lymphocytic 880:890 arg1 malignancies 892:903 lymphocytic malignancies 880:903 lymphocytic malignancies 880:903 Altogether, 404 cell surface N-glycoproteins were identified as markers for specific cell types involved in lymphocytic malignancies, including 82 N-glycoproteins that had not been previously been described for B or T cells within the Cell Surface Protein Atlas. 28834292 6 35 theme lymphocytic 880:890 arg1 N-glycoproteins 919:933 82 N-glycoproteins 916:933 82 N-glycoproteins that had not been previously been described for B or T cells within the Cell Surface Protein Atlas 916:1032 Altogether, 404 cell surface N-glycoproteins were identified as markers for specific cell types involved in lymphocytic malignancies, including 82 N-glycoproteins that had not been previously been described for B or T cells within the Cell Surface Protein Atlas. 28834292 8 36 theme first 1280:1284 arg1 step 1286:1289 a first step 1278:1289 a first step toward improving personalized diagnosis and treatment of leukemia and lymphoma 1278:1368 Undoubtedly, the characterization of the cell surface proteome of lymphoid malignancies is a first step toward improving personalized diagnosis and treatment of leukemia and lymphoma. 28834292 8 36 theme first 1280:1284 arg1 characterization 1204:1219 the characterization 1200:1219 the characterization of the cell surface proteome of lymphoid malignancies 1200:1273 Undoubtedly, the characterization of the cell surface proteome of lymphoid malignancies is a first step toward improving personalized diagnosis and treatment of leukemia and lymphoma. 28834292 0 37 theme Glycoproteins 36:48 arg1 Proteomics 13:22 Cell Surface Proteomics 0:22 Cell Surface Proteomics of N-Linked Glycoproteins for Typing of Human Lymphocytes. 0:81 Cell Surface Proteomics of N-Linked Glycoproteins for Typing of Human Lymphocytes. 28834292 4 38 theme lymphoid 558:565 arg1 malignancies 567:578 lymphoid malignancies 558:578 lymphoid malignancies 558:578 One viable means of classification involves evaluation of the cell surface proteome of lymphoid malignancies. 28834292 7 39 theme clustering 1070:1079 arg1 techniques 1081:1090 hierarchical clustering techniques 1057:1090 hierarchical clustering techniques 1057:1090 Comparative analysis, hierarchical clustering techniques, and label-free quantitation were used to reveal proteins most informative for each cell type. 28834292 0 40 theme N-Linked 27:34 arg1 Glycoproteins 36:48 N-Linked Glycoproteins 27:48 N-Linked Glycoproteins 27:48 Cell Surface Proteomics of N-Linked Glycoproteins for Typing of Human Lymphocytes. 28834292 7 41 theme cell 1176:1179 arg1 type 1181:1184 each cell type 1171:1184 each cell type 1171:1184 Comparative analysis, hierarchical clustering techniques, and label-free quantitation were used to reveal proteins most informative for each cell type. 28834292 3 42 theme present 450:456 arg1 states 443:448 distinct disease states 426:448 distinct disease states present in patients 426:468 Therefore, it is imperative a precise method of cell categorization is utilized to detect differences in distinct disease states present in patients. 28834292 7 43 theme informative 1155:1165 arg1 proteins 1141:1148 proteins 1141:1148 proteins most informative for each cell type 1141:1184 Comparative analysis, hierarchical clustering techniques, and label-free quantitation were used to reveal proteins most informative for each cell type. 28834292 3 44 used utilized 392:399 arg2 method 359:364 a precise method 349:364 a precise method of cell categorization 349:387 Therefore, it is imperative a precise method of cell categorization is utilized to detect differences in distinct disease states present in patients. 28834292 3 45 theme distinct 426:433 arg1 states 443:448 distinct disease states 426:448 distinct disease states present in patients 426:468 Therefore, it is imperative a precise method of cell categorization is utilized to detect differences in distinct disease states present in patients. 28834292 2 46 theme T- 223:224 arg1 subtypes 239:246 B-, T-, and NK-cell subtypes 219:246 B-, T-, and NK-cell subtypes that individually correlate with specific forms of leukemia or lymphoma 219:318 Differentiation of lymphoid progenitors yields B-, T-, and NK-cell subtypes that individually correlate with specific forms of leukemia or lymphoma. 28834292 3 47 from present 450:456 arg1 patients 461:468 patients 461:468 patients 461:468 Therefore, it is imperative a precise method of cell categorization is utilized to detect differences in distinct disease states present in patients. 28834292 8 48 theme proteome 1241:1248 arg1 step 1286:1289 a first step 1278:1289 a first step toward improving personalized diagnosis and treatment of leukemia and lymphoma 1278:1368 Undoubtedly, the characterization of the cell surface proteome of lymphoid malignancies is a first step toward improving personalized diagnosis and treatment of leukemia and lymphoma. 28834292 8 48 theme proteome 1241:1248 arg1 characterization 1204:1219 the characterization 1200:1219 the characterization of the cell surface proteome of lymphoid malignancies 1200:1273 Undoubtedly, the characterization of the cell surface proteome of lymphoid malignancies is a first step toward improving personalized diagnosis and treatment of leukemia and lymphoma. 28834292 4 49 theme surface 538:544 arg1 proteome 546:553 the cell surface proteome 529:553 the cell surface proteome of lymphoid malignancies 529:578 One viable means of classification involves evaluation of the cell surface proteome of lymphoid malignancies. 28834292 5 50 theme Capture 685:691 arg1 Technology 693:702 Cell Surface Capture Technology 672:702 Cell Surface Capture Technology 672:702 Specifically, this manuscript details the use of an antibody independent approach known as Cell Surface Capture Technology, to assess the N-glycoproteome of four human lymphocyte cell lines. 28834292 2 51 theme B- 219:220 arg1 subtypes 239:246 B-, T-, and NK-cell subtypes 219:246 B-, T-, and NK-cell subtypes that individually correlate with specific forms of leukemia or lymphoma 219:318 Differentiation of lymphoid progenitors yields B-, T-, and NK-cell subtypes that individually correlate with specific forms of leukemia or lymphoma. 28834292 8 52 theme personalized 1308:1319 arg1 diagnosis 1321:1329 personalized diagnosis 1308:1329 personalized diagnosis 1308:1329 Undoubtedly, the characterization of the cell surface proteome of lymphoid malignancies is a first step toward improving personalized diagnosis and treatment of leukemia and lymphoma. 28834292 4 53 theme cell 533:536 arg1 proteome 546:553 the cell surface proteome 529:553 the cell surface proteome of lymphoid malignancies 529:578 One viable means of classification involves evaluation of the cell surface proteome of lymphoid malignancies. 28834292 7 54 theme Comparative 1035:1045 arg1 analysis 1047:1054 Comparative analysis 1035:1054 Comparative analysis 1035:1054 Comparative analysis, hierarchical clustering techniques, and label-free quantitation were used to reveal proteins most informative for each cell type. 28834292 6 55 theme specific 848:855 arg1 types 862:866 specific cell types 848:866 specific cell types involved in lymphocytic malignancies, including 82 N-glycoproteins that had not been previously been described for B or T cells within the Cell Surface Protein Atlas 848:1032 Altogether, 404 cell surface N-glycoproteins were identified as markers for specific cell types involved in lymphocytic malignancies, including 82 N-glycoproteins that had not been previously been described for B or T cells within the Cell Surface Protein Atlas. 28834292 3 56 from patients 461:468 arg1 present 450:456 present 450:456 present 450:456 Therefore, it is imperative a precise method of cell categorization is utilized to detect differences in distinct disease states present in patients. 28834292 1 57 theme immune 99:104 arg1 Lymphocytes 83:93 Lymphocytes 83:93 Lymphocytes 83:93 Lymphocytes are immune cells that are critical for the maintenance of adaptive immunity. 28834292 1 57 theme immune 99:104 arg1 cells 106:110 immune cells 99:110 immune cells that are critical for the maintenance of adaptive immunity 99:169 Lymphocytes are immune cells that are critical for the maintenance of adaptive immunity. 28834292 7 58 used used 1126:1129 arg2 techniques 1081:1090 hierarchical clustering techniques 1057:1090 hierarchical clustering techniques 1057:1090 Comparative analysis, hierarchical clustering techniques, and label-free quantitation were used to reveal proteins most informative for each cell type. 28834292 7 58 used used 1126:1129 arg2 quantitation 1108:1119 label-free quantitation 1097:1119 label-free quantitation 1097:1119 Comparative analysis, hierarchical clustering techniques, and label-free quantitation were used to reveal proteins most informative for each cell type. 28834292 7 58 used used 1126:1129 arg2 analysis 1047:1054 Comparative analysis 1035:1054 Comparative analysis 1035:1054 Comparative analysis, hierarchical clustering techniques, and label-free quantitation were used to reveal proteins most informative for each cell type. 28834292 2 59 theme progenitors 200:210 arg1 Differentiation 172:186 Differentiation 172:186 Differentiation of lymphoid progenitors 172:210 Differentiation of lymphoid progenitors yields B-, T-, and NK-cell subtypes that individually correlate with specific forms of leukemia or lymphoma. 28834292 3 60 from differences 411:421 arg1 states 443:448 distinct disease states 426:448 distinct disease states present in patients 426:468 Therefore, it is imperative a precise method of cell categorization is utilized to detect differences in distinct disease states present in patients. 28834292 8 61 theme cell 1228:1231 arg1 proteome 1241:1248 the cell surface proteome 1224:1248 the cell surface proteome of lymphoid malignancies 1224:1273 Undoubtedly, the characterization of the cell surface proteome of lymphoid malignancies is a first step toward improving personalized diagnosis and treatment of leukemia and lymphoma. 28834292 0 62 theme Human 64:68 arg1 Lymphocytes 70:80 Human Lymphocytes 64:80 Human Lymphocytes 64:80 Cell Surface Proteomics of N-Linked Glycoproteins for Typing of Human Lymphocytes. 28834292 2 63 theme lymphoid 191:198 arg1 progenitors 200:210 lymphoid progenitors 191:210 lymphoid progenitors 191:210 Differentiation of lymphoid progenitors yields B-, T-, and NK-cell subtypes that individually correlate with specific forms of leukemia or lymphoma. 28834292 8 64 theme leukemia 1348:1355 arg1 treatment 1335:1343 treatment 1335:1343 treatment 1335:1343 Undoubtedly, the characterization of the cell surface proteome of lymphoid malignancies is a first step toward improving personalized diagnosis and treatment of leukemia and lymphoma. 28834292 8 64 theme leukemia 1348:1355 arg1 diagnosis 1321:1329 personalized diagnosis 1308:1329 personalized diagnosis 1308:1329 Undoubtedly, the characterization of the cell surface proteome of lymphoid malignancies is a first step toward improving personalized diagnosis and treatment of leukemia and lymphoma. 28834292 8 65 theme lymphoid 1253:1260 arg1 malignancies 1262:1273 lymphoid malignancies 1253:1273 lymphoid malignancies 1253:1273 Undoubtedly, the characterization of the cell surface proteome of lymphoid malignancies is a first step toward improving personalized diagnosis and treatment of leukemia and lymphoma. 28834292 6 66 theme Protein 1020:1026 arg1 Atlas 1028:1032 the Cell Surface Protein Atlas 1003:1032 the Cell Surface Protein Atlas 1003:1032 Altogether, 404 cell surface N-glycoproteins were identified as markers for specific cell types involved in lymphocytic malignancies, including 82 N-glycoproteins that had not been previously been described for B or T cells within the Cell Surface Protein Atlas. 28834292 5 67 theme lines 765:769 arg1 N-glycoproteome 719:733 the N-glycoproteome 715:733 the N-glycoproteome of four human lymphocyte cell lines 715:769 Specifically, this manuscript details the use of an antibody independent approach known as Cell Surface Capture Technology, to assess the N-glycoproteome of four human lymphocyte cell lines. 28834292 4 68 theme classification 491:504 arg1 means 482:486 One viable means 471:486 One viable means of classification 471:504 One viable means of classification involves evaluation of the cell surface proteome of lymphoid malignancies. 28834292 2 69 theme NK-cell 231:237 arg1 subtypes 239:246 B-, T-, and NK-cell subtypes 219:246 B-, T-, and NK-cell subtypes that individually correlate with specific forms of leukemia or lymphoma 219:318 Differentiation of lymphoid progenitors yields B-, T-, and NK-cell subtypes that individually correlate with specific forms of leukemia or lymphoma. 28834292 8 70 theme malignancies 1262:1273 arg1 proteome 1241:1248 the cell surface proteome 1224:1248 the cell surface proteome of lymphoid malignancies 1224:1273 Undoubtedly, the characterization of the cell surface proteome of lymphoid malignancies is a first step toward improving personalized diagnosis and treatment of leukemia and lymphoma. 28834292 3 71 theme cell 369:372 arg1 categorization 374:387 cell categorization 369:387 cell categorization 369:387 Therefore, it is imperative a precise method of cell categorization is utilized to detect differences in distinct disease states present in patients. 28834292 6 72 theme Surface 1012:1018 arg1 Atlas 1028:1032 the Cell Surface Protein Atlas 1003:1032 the Cell Surface Protein Atlas 1003:1032 Altogether, 404 cell surface N-glycoproteins were identified as markers for specific cell types involved in lymphocytic malignancies, including 82 N-glycoproteins that had not been previously been described for B or T cells within the Cell Surface Protein Atlas. 28145111 1 0 gly glycoproteins 314:326 arg1 glycoproteins 314:326 MFGM glycoproteins 309:326 MFGM glycoproteins 309:326 The health-promoting effects of milk fat globule membrane (MFGM) glycoconjugates has attracted curiosity especially with regard to the challenges encountered to unravel the glycan complexities of MFGM glycoproteins and glycosphingolipids. 28145111 1 1 theme fat 150:152 arg1 glycoconjugates 178:192 milk fat globule membrane (MFGM) glycoconjugates 145:192 milk fat globule membrane (MFGM) glycoconjugates 145:192 The health-promoting effects of milk fat globule membrane (MFGM) glycoconjugates has attracted curiosity especially with regard to the challenges encountered to unravel the glycan complexities of MFGM glycoproteins and glycosphingolipids. 28145111 6 2 theme Core 1038:1041 arg1 O-glycans 1045:1053 Core 1 O-glycans 1038:1053 Core 1 O-glycans 1038:1053 Core 1 O-glycans were more common in both samples, and the major glycosphingolipids were GM3 and GD3 irrespective of the samples analyzed. 28145111 2 3 theme MALDI-TOF 517:525 arg1 analysis 531:538 matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS analysis 457:538 matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS analysis 457:538 In this context, we characterized glycans present in buffalo milk and colostrum fat globule membranes by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS analysis by adopting chemoselective glycoblotting technique. 28145111 4 4 theme disialyl 888:895 arg1 glycans 897:903 mono- and disialyl glycans 878:903 mono- and disialyl glycans 878:903 Among N-linked glycans, mono-, di-, and trisialyl glycans were apparent in colostrum, while MFGM predominantly contained mono- and disialyl glycans, in addition to neutral and high-mannose glycoforms. 28145111 1 5 theme globule 154:160 arg1 glycoconjugates 178:192 milk fat globule membrane (MFGM) glycoconjugates 145:192 milk fat globule membrane (MFGM) glycoconjugates 145:192 The health-promoting effects of milk fat globule membrane (MFGM) glycoconjugates has attracted curiosity especially with regard to the challenges encountered to unravel the glycan complexities of MFGM glycoproteins and glycosphingolipids. 28145111 2 6 theme glycoblotting 567:579 arg1 technique 581:589 chemoselective glycoblotting technique 552:589 chemoselective glycoblotting technique 552:589 In this context, we characterized glycans present in buffalo milk and colostrum fat globule membranes by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS analysis by adopting chemoselective glycoblotting technique. 28145111 7 7 from relationship 1293:1304 arg1 milk 1335:1338 early milk 1329:1338 early milk 1329:1338 The colostrum N-glycans, being effective antibacterials against human pathogens, established the structure-function relationship of oligosaccharides in early milk in providing innate protection to the newborn. 28145111 4 8 link N-linked 763:770 arg1 glycans 772:778 N-linked glycans 763:778 N-linked glycans 763:778 Among N-linked glycans, mono-, di-, and trisialyl glycans were apparent in colostrum, while MFGM predominantly contained mono- and disialyl glycans, in addition to neutral and high-mannose glycoforms. 28145111 3 9 theme bovine 609:614 arg1 glycoproteins 621:633 human and bovine MFGM glycoproteins 599:633 human and bovine MFGM glycoproteins 599:633 Unlike human and bovine MFGM glycoproteins, the variations were obvious with respect to their number, size, heterogeneity, and abundance among the samples analyzed. 28145111 2 10 theme chemoselective 552:565 arg1 technique 581:589 chemoselective glycoblotting technique 552:589 chemoselective glycoblotting technique 552:589 In this context, we characterized glycans present in buffalo milk and colostrum fat globule membranes by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS analysis by adopting chemoselective glycoblotting technique. 28145111 4 11 theme di- 788:790 arg1 glycans 807:813 mono-, di-, and trisialyl glycans 781:813 mono-, di-, and trisialyl glycans 781:813 Among N-linked glycans, mono-, di-, and trisialyl glycans were apparent in colostrum, while MFGM predominantly contained mono- and disialyl glycans, in addition to neutral and high-mannose glycoforms. 28145111 3 12 theme human 599:603 arg1 glycoproteins 621:633 human and bovine MFGM glycoproteins 599:633 human and bovine MFGM glycoproteins 599:633 Unlike human and bovine MFGM glycoproteins, the variations were obvious with respect to their number, size, heterogeneity, and abundance among the samples analyzed. 28145111 7 13 theme early 1329:1333 arg1 milk 1335:1338 early milk 1329:1338 early milk 1329:1338 The colostrum N-glycans, being effective antibacterials against human pathogens, established the structure-function relationship of oligosaccharides in early milk in providing innate protection to the newborn. 28145111 4 14 dep glycoforms 946:955 arg1 addition 909:916 addition 909:916 addition 909:916 Among N-linked glycans, mono-, di-, and trisialyl glycans were apparent in colostrum, while MFGM predominantly contained mono- and disialyl glycans, in addition to neutral and high-mannose glycoforms. 28145111 6 15 theme major 1097:1101 arg1 GM3 1127:1129 GM3 1127:1129 GM3 1127:1129 Core 1 O-glycans were more common in both samples, and the major glycosphingolipids were GM3 and GD3 irrespective of the samples analyzed. 28145111 6 15 theme major 1097:1101 arg1 glycosphingolipids 1103:1120 the major glycosphingolipids 1093:1120 the major glycosphingolipids 1093:1120 Core 1 O-glycans were more common in both samples, and the major glycosphingolipids were GM3 and GD3 irrespective of the samples analyzed. 28145111 4 16 theme trisialyl 797:805 arg1 glycans 807:813 mono-, di-, and trisialyl glycans 781:813 mono-, di-, and trisialyl glycans 781:813 Among N-linked glycans, mono-, di-, and trisialyl glycans were apparent in colostrum, while MFGM predominantly contained mono- and disialyl glycans, in addition to neutral and high-mannose glycoforms. 28145111 2 17 theme present 394:400 arg1 glycans 386:392 glycans 386:392 glycans present in buffalo milk and colostrum fat globule membranes 386:452 In this context, we characterized glycans present in buffalo milk and colostrum fat globule membranes by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS analysis by adopting chemoselective glycoblotting technique. 28145111 1 18 theme membrane 162:169 arg1 glycoconjugates 178:192 milk fat globule membrane (MFGM) glycoconjugates 145:192 milk fat globule membrane (MFGM) glycoconjugates 145:192 The health-promoting effects of milk fat globule membrane (MFGM) glycoconjugates has attracted curiosity especially with regard to the challenges encountered to unravel the glycan complexities of MFGM glycoproteins and glycosphingolipids. 28145111 2 19 theme laser 473:477 arg1 desorption/ionization 479:499 matrix-assisted laser desorption/ionization 457:499 matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS analysis 457:538 In this context, we characterized glycans present in buffalo milk and colostrum fat globule membranes by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS analysis by adopting chemoselective glycoblotting technique. 28145111 5 20 theme structural 962:971 arg1 assignments 973:983 The structural assignments 958:983 The structural assignments of major glycans 958:1000 The structural assignments of major glycans were confirmed by TOF/TOF analysis. 28145111 7 21 theme effective 1208:1216 arg1 antibacterials 1218:1231 effective antibacterials 1208:1231 effective antibacterials 1208:1231 The colostrum N-glycans, being effective antibacterials against human pathogens, established the structure-function relationship of oligosaccharides in early milk in providing innate protection to the newborn. 28145111 2 22 theme matrix-assisted 457:471 arg1 desorption/ionization 479:499 matrix-assisted laser desorption/ionization 457:499 matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS analysis 457:538 In this context, we characterized glycans present in buffalo milk and colostrum fat globule membranes by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS analysis by adopting chemoselective glycoblotting technique. 28145111 6 23 from common 1065:1070 arg1 samples 1080:1086 both samples 1075:1086 both samples 1075:1086 Core 1 O-glycans were more common in both samples, and the major glycosphingolipids were GM3 and GD3 irrespective of the samples analyzed. 28145111 3 24 theme MFGM 616:619 arg1 glycoproteins 621:633 human and bovine MFGM glycoproteins 599:633 human and bovine MFGM glycoproteins 599:633 Unlike human and bovine MFGM glycoproteins, the variations were obvious with respect to their number, size, heterogeneity, and abundance among the samples analyzed. 28145111 1 25 theme MFGM 172:175 arg1 glycoconjugates 178:192 milk fat globule membrane (MFGM) glycoconjugates 145:192 milk fat globule membrane (MFGM) glycoconjugates 145:192 The health-promoting effects of milk fat globule membrane (MFGM) glycoconjugates has attracted curiosity especially with regard to the challenges encountered to unravel the glycan complexities of MFGM glycoproteins and glycosphingolipids. 28145111 0 26 theme Comparative 0:10 arg1 Glycomics 12:20 Comparative Glycomics 0:20 Comparative Glycomics of Fat Globule Membrane Glycoconjugates from Buffalo (Bubalus bubalis) Milk and Colostrum. 0:111 Comparative Glycomics of Fat Globule Membrane Glycoconjugates from Buffalo (Bubalus bubalis) Milk and Colostrum. 28145111 4 27 theme mono- 878:882 arg1 glycans 897:903 mono- and disialyl glycans 878:903 mono- and disialyl glycans 878:903 Among N-linked glycans, mono-, di-, and trisialyl glycans were apparent in colostrum, while MFGM predominantly contained mono- and disialyl glycans, in addition to neutral and high-mannose glycoforms. 28145111 6 28 from samples 1080:1086 arg1 common 1065:1070 common 1065:1070 common 1065:1070 Core 1 O-glycans were more common in both samples, and the major glycosphingolipids were GM3 and GD3 irrespective of the samples analyzed. 28145111 2 29 theme buffalo 405:411 arg1 milk 413:416 buffalo milk 405:416 buffalo milk 405:416 In this context, we characterized glycans present in buffalo milk and colostrum fat globule membranes by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS analysis by adopting chemoselective glycoblotting technique. 28145111 0 30 theme Fat 25:27 arg1 Glycoconjugates 46:60 Fat Globule Membrane Glycoconjugates 25:60 Fat Globule Membrane Glycoconjugates 25:60 Comparative Glycomics of Fat Globule Membrane Glycoconjugates from Buffalo (Bubalus bubalis) Milk and Colostrum. 28145111 1 31 theme glycoconjugates 178:192 arg1 effects 134:140 The health-promoting effects 113:140 The health-promoting effects of milk fat globule membrane (MFGM) glycoconjugates 113:192 The health-promoting effects of milk fat globule membrane (MFGM) glycoconjugates has attracted curiosity especially with regard to the challenges encountered to unravel the glycan complexities of MFGM glycoproteins and glycosphingolipids. 28145111 2 32 theme globule 436:442 arg1 membranes 444:452 globule membranes 436:452 globule membranes 436:452 In this context, we characterized glycans present in buffalo milk and colostrum fat globule membranes by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS analysis by adopting chemoselective glycoblotting technique. 28145111 1 33 theme glycan 286:291 arg1 complexities 293:304 the glycan complexities 282:304 the glycan complexities of MFGM glycoproteins and glycosphingolipids 282:349 The health-promoting effects of milk fat globule membrane (MFGM) glycoconjugates has attracted curiosity especially with regard to the challenges encountered to unravel the glycan complexities of MFGM glycoproteins and glycosphingolipids. 28145111 4 34 theme high-mannose 933:944 arg1 glycoforms 946:955 neutral and high-mannose glycoforms 921:955 neutral and high-mannose glycoforms 921:955 Among N-linked glycans, mono-, di-, and trisialyl glycans were apparent in colostrum, while MFGM predominantly contained mono- and disialyl glycans, in addition to neutral and high-mannose glycoforms. 28145111 0 35 dep Buffalo 67:73 arg1 Milk 93:96 Milk 93:96 Milk 93:96 Comparative Glycomics of Fat Globule Membrane Glycoconjugates from Buffalo (Bubalus bubalis) Milk and Colostrum. 28145111 0 35 dep Buffalo 67:73 arg1 Colostrum 102:110 Colostrum 102:110 Colostrum 102:110 Comparative Glycomics of Fat Globule Membrane Glycoconjugates from Buffalo (Bubalus bubalis) Milk and Colostrum. 28145111 2 36 theme colostrum 422:430 arg1 fat 432:434 colostrum fat 422:434 colostrum fat 422:434 In this context, we characterized glycans present in buffalo milk and colostrum fat globule membranes by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS analysis by adopting chemoselective glycoblotting technique. 28145111 0 37 theme Membrane 37:44 arg1 Glycoconjugates 46:60 Fat Globule Membrane Glycoconjugates 25:60 Fat Globule Membrane Glycoconjugates 25:60 Comparative Glycomics of Fat Globule Membrane Glycoconjugates from Buffalo (Bubalus bubalis) Milk and Colostrum. 28145111 0 38 theme Globule 29:35 arg1 Glycoconjugates 46:60 Fat Globule Membrane Glycoconjugates 25:60 Fat Globule Membrane Glycoconjugates 25:60 Comparative Glycomics of Fat Globule Membrane Glycoconjugates from Buffalo (Bubalus bubalis) Milk and Colostrum. 28145111 2 39 theme time-of-flight 501:514 arg1 analysis 531:538 matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS analysis 457:538 matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS analysis 457:538 In this context, we characterized glycans present in buffalo milk and colostrum fat globule membranes by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS analysis by adopting chemoselective glycoblotting technique. 28145111 2 40 dep milk 413:416 arg1 membranes 444:452 globule membranes 436:452 globule membranes 436:452 In this context, we characterized glycans present in buffalo milk and colostrum fat globule membranes by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS analysis by adopting chemoselective glycoblotting technique. 28145111 2 41 from present 394:400 arg1 milk 413:416 buffalo milk 405:416 buffalo milk 405:416 In this context, we characterized glycans present in buffalo milk and colostrum fat globule membranes by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS analysis by adopting chemoselective glycoblotting technique. 28145111 2 41 from present 394:400 arg1 fat 432:434 colostrum fat 422:434 colostrum fat 422:434 In this context, we characterized glycans present in buffalo milk and colostrum fat globule membranes by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS analysis by adopting chemoselective glycoblotting technique. 28145111 7 42 theme innate 1353:1358 arg1 protection 1360:1369 innate protection 1353:1369 innate protection 1353:1369 The colostrum N-glycans, being effective antibacterials against human pathogens, established the structure-function relationship of oligosaccharides in early milk in providing innate protection to the newborn. 28145111 2 43 theme desorption/ionization 479:499 arg1 analysis 531:538 matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS analysis 457:538 matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS analysis 457:538 In this context, we characterized glycans present in buffalo milk and colostrum fat globule membranes by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS analysis by adopting chemoselective glycoblotting technique. 28145111 1 44 theme MFGM 309:312 arg1 glycoproteins 314:326 MFGM glycoproteins 309:326 MFGM glycoproteins 309:326 The health-promoting effects of milk fat globule membrane (MFGM) glycoconjugates has attracted curiosity especially with regard to the challenges encountered to unravel the glycan complexities of MFGM glycoproteins and glycosphingolipids. 28145111 0 45 from Buffalo 67:73 arg1 Glycomics 12:20 Comparative Glycomics 0:20 Comparative Glycomics of Fat Globule Membrane Glycoconjugates from Buffalo (Bubalus bubalis) Milk and Colostrum. 0:111 Comparative Glycomics of Fat Globule Membrane Glycoconjugates from Buffalo (Bubalus bubalis) Milk and Colostrum. 28145111 3 46 gly glycoproteins 621:633 arg1 glycoproteins 621:633 human and bovine MFGM glycoproteins 599:633 human and bovine MFGM glycoproteins 599:633 Unlike human and bovine MFGM glycoproteins, the variations were obvious with respect to their number, size, heterogeneity, and abundance among the samples analyzed. 28145111 0 47 theme Glycoconjugates 46:60 arg1 Glycomics 12:20 Comparative Glycomics 0:20 Comparative Glycomics of Fat Globule Membrane Glycoconjugates from Buffalo (Bubalus bubalis) Milk and Colostrum. 0:111 Comparative Glycomics of Fat Globule Membrane Glycoconjugates from Buffalo (Bubalus bubalis) Milk and Colostrum. 28145111 1 48 theme glycoproteins 314:326 arg1 complexities 293:304 the glycan complexities 282:304 the glycan complexities of MFGM glycoproteins and glycosphingolipids 282:349 The health-promoting effects of milk fat globule membrane (MFGM) glycoconjugates has attracted curiosity especially with regard to the challenges encountered to unravel the glycan complexities of MFGM glycoproteins and glycosphingolipids. 28145111 4 49 from apparent 820:827 arg1 colostrum 832:840 colostrum 832:840 colostrum 832:840 Among N-linked glycans, mono-, di-, and trisialyl glycans were apparent in colostrum, while MFGM predominantly contained mono- and disialyl glycans, in addition to neutral and high-mannose glycoforms. 28145111 7 50 theme colostrum 1181:1189 arg1 N-glycans 1191:1199 The colostrum N-glycans 1177:1199 The colostrum N-glycans 1177:1199 The colostrum N-glycans, being effective antibacterials against human pathogens, established the structure-function relationship of oligosaccharides in early milk in providing innate protection to the newborn. 28145111 5 51 theme TOF/TOF 1020:1026 arg1 analysis 1028:1035 TOF/TOF analysis 1020:1035 TOF/TOF analysis 1020:1035 The structural assignments of major glycans were confirmed by TOF/TOF analysis. 28145111 4 52 from colostrum 832:840 arg1 apparent 820:827 apparent 820:827 apparent 820:827 Among N-linked glycans, mono-, di-, and trisialyl glycans were apparent in colostrum, while MFGM predominantly contained mono- and disialyl glycans, in addition to neutral and high-mannose glycoforms. 28145111 1 53 theme health-promoting 117:132 arg1 effects 134:140 The health-promoting effects 113:140 The health-promoting effects of milk fat globule membrane (MFGM) glycoconjugates 113:192 The health-promoting effects of milk fat globule membrane (MFGM) glycoconjugates has attracted curiosity especially with regard to the challenges encountered to unravel the glycan complexities of MFGM glycoproteins and glycosphingolipids. 28145111 4 54 theme neutral 921:927 arg1 glycoforms 946:955 neutral and high-mannose glycoforms 921:955 neutral and high-mannose glycoforms 921:955 Among N-linked glycans, mono-, di-, and trisialyl glycans were apparent in colostrum, while MFGM predominantly contained mono- and disialyl glycans, in addition to neutral and high-mannose glycoforms. 28145111 5 55 theme glycans 994:1000 arg1 assignments 973:983 The structural assignments 958:983 The structural assignments of major glycans 958:1000 The structural assignments of major glycans were confirmed by TOF/TOF analysis. 28145111 4 56 theme mono- 781:785 arg1 glycans 807:813 mono-, di-, and trisialyl glycans 781:813 mono-, di-, and trisialyl glycans 781:813 Among N-linked glycans, mono-, di-, and trisialyl glycans were apparent in colostrum, while MFGM predominantly contained mono- and disialyl glycans, in addition to neutral and high-mannose glycoforms. 28145111 7 57 theme oligosaccharides 1309:1324 arg1 relationship 1293:1304 the structure-function relationship 1270:1304 the structure-function relationship of oligosaccharides in early milk 1270:1338 The colostrum N-glycans, being effective antibacterials against human pathogens, established the structure-function relationship of oligosaccharides in early milk in providing innate protection to the newborn. 28145111 4 58 theme N-linked 763:770 arg1 glycans 772:778 N-linked glycans 763:778 N-linked glycans 763:778 Among N-linked glycans, mono-, di-, and trisialyl glycans were apparent in colostrum, while MFGM predominantly contained mono- and disialyl glycans, in addition to neutral and high-mannose glycoforms. 28145111 2 59 attach present 394:400 arg2 glycans 386:392 glycans 386:392 glycans present in buffalo milk and colostrum fat globule membranes 386:452 In this context, we characterized glycans present in buffalo milk and colostrum fat globule membranes by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS analysis by adopting chemoselective glycoblotting technique. 28145111 2 59 attach present 394:400 arg1 milk 413:416 buffalo milk 405:416 buffalo milk 405:416 In this context, we characterized glycans present in buffalo milk and colostrum fat globule membranes by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS analysis by adopting chemoselective glycoblotting technique. 28145111 2 59 attach present 394:400 arg1 fat 432:434 colostrum fat 422:434 colostrum fat 422:434 In this context, we characterized glycans present in buffalo milk and colostrum fat globule membranes by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS analysis by adopting chemoselective glycoblotting technique. 28145111 2 60 from milk 413:416 arg1 present 394:400 present 394:400 present 394:400 In this context, we characterized glycans present in buffalo milk and colostrum fat globule membranes by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS analysis by adopting chemoselective glycoblotting technique. 28145111 5 61 theme major 988:992 arg1 glycans 994:1000 major glycans 988:1000 major glycans 988:1000 The structural assignments of major glycans were confirmed by TOF/TOF analysis. 28145111 4 62 contain contained 868:876 arg2 glycans 897:903 mono- and disialyl glycans 878:903 mono- and disialyl glycans 878:903 Among N-linked glycans, mono-, di-, and trisialyl glycans were apparent in colostrum, while MFGM predominantly contained mono- and disialyl glycans, in addition to neutral and high-mannose glycoforms. 28145111 4 62 contain contained 868:876 arg1 MFGM 849:852 MFGM 849:852 MFGM 849:852 Among N-linked glycans, mono-, di-, and trisialyl glycans were apparent in colostrum, while MFGM predominantly contained mono- and disialyl glycans, in addition to neutral and high-mannose glycoforms. 28145111 2 63 theme MS 528:529 arg1 analysis 531:538 matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS analysis 457:538 matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS analysis 457:538 In this context, we characterized glycans present in buffalo milk and colostrum fat globule membranes by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS analysis by adopting chemoselective glycoblotting technique. 28145111 1 64 theme glycosphingolipids 332:349 arg1 complexities 293:304 the glycan complexities 282:304 the glycan complexities of MFGM glycoproteins and glycosphingolipids 282:349 The health-promoting effects of milk fat globule membrane (MFGM) glycoconjugates has attracted curiosity especially with regard to the challenges encountered to unravel the glycan complexities of MFGM glycoproteins and glycosphingolipids. 28145111 2 65 from fat 432:434 arg1 present 394:400 present 394:400 present 394:400 In this context, we characterized glycans present in buffalo milk and colostrum fat globule membranes by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS analysis by adopting chemoselective glycoblotting technique. 28145111 1 66 theme milk 145:148 arg1 glycoconjugates 178:192 milk fat globule membrane (MFGM) glycoconjugates 145:192 milk fat globule membrane (MFGM) glycoconjugates 145:192 The health-promoting effects of milk fat globule membrane (MFGM) glycoconjugates has attracted curiosity especially with regard to the challenges encountered to unravel the glycan complexities of MFGM glycoproteins and glycosphingolipids. 28145111 7 67 theme structure-function 1274:1291 arg1 relationship 1293:1304 the structure-function relationship 1270:1304 the structure-function relationship of oligosaccharides in early milk 1270:1338 The colostrum N-glycans, being effective antibacterials against human pathogens, established the structure-function relationship of oligosaccharides in early milk in providing innate protection to the newborn. 28145111 7 68 theme human 1241:1245 arg1 pathogens 1247:1255 human pathogens 1241:1255 human pathogens 1241:1255 The colostrum N-glycans, being effective antibacterials against human pathogens, established the structure-function relationship of oligosaccharides in early milk in providing innate protection to the newborn. 26021314 6 0 theme O-linked 1122:1129 arg1 glycoproteins 1131:1143 O-linked glycoproteins 1122:1143 O-linked glycoproteins 1122:1143 METHODS Forced expression of Tn antigen on O-glycosylated proteins in pancreatic cancer cells was induced by lentiviral-mediated knockdown of the COSMC chaperone, which prevented O-glycan elongation beyond the initial GalNAcα1- residue on O-linked glycoproteins. 26021314 10 1 dep derived 1707:1713 arg1 patient 1699:1705 patient 1699:1705 patient 1699:1705 Expression of Tn antigen bearing Nucleolin in patient derived PDAC tumor specimens was evaluated and correlated with clinicopathological data. 26021314 2 2 theme truncated 346:354 arg1 glycosylation 396:408 a truncated O-linked N-acetylgalactosamine (GalNAc) glycosylation 344:408 a truncated O-linked N-acetylgalactosamine (GalNAc) glycosylation with expression of the Tn antigen 344:442 A frequently detected alteration in PDACs is a truncated O-linked N-acetylgalactosamine (GalNAc) glycosylation with expression of the Tn antigen. 26021314 2 2 theme truncated 346:354 arg1 alteration 321:330 A frequently detected alteration 299:330 A frequently detected alteration in PDACs 299:339 A frequently detected alteration in PDACs is a truncated O-linked N-acetylgalactosamine (GalNAc) glycosylation with expression of the Tn antigen. 26021314 1 3 theme research 255:262 arg1 types 264:268 research types 255:268 research types of treatment 255:281 BACKGROUND Human pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal malignancies in the world and despite great efforts in research types of treatment remain limited. 26021314 2 4 with glycosylation 396:408 arg1 expression 415:424 expression 415:424 expression of the Tn antigen 415:442 A frequently detected alteration in PDACs is a truncated O-linked N-acetylgalactosamine (GalNAc) glycosylation with expression of the Tn antigen. 26021314 13 5 from protein 2239:2245 arg1 lines 2276:2280 COSMC deficient PDAC cell lines 2250:2280 COSMC deficient PDAC cell lines 2250:2280 Nucleolin was identified as O-GalNAc modified protein in COSMC deficient PDAC cell lines. 26021314 6 6 from METHODS 883:889 arg1 expression 898:907 Forced expression 891:907 Forced expression of Tn antigen 891:921 METHODS Forced expression of Tn antigen on O-glycosylated proteins in pancreatic cancer cells was induced by lentiviral-mediated knockdown of the COSMC chaperone, which prevented O-glycan elongation beyond the initial GalNAcα1- residue on O-linked glycoproteins. 26021314 2 7 link O-linked 356:363 arg1 glycosylation 396:408 a truncated O-linked N-acetylgalactosamine (GalNAc) glycosylation 344:408 a truncated O-linked N-acetylgalactosamine (GalNAc) glycosylation with expression of the Tn antigen 344:442 A frequently detected alteration in PDACs is a truncated O-linked N-acetylgalactosamine (GalNAc) glycosylation with expression of the Tn antigen. 26021314 2 7 link O-linked 356:363 arg1 alteration 321:330 A frequently detected alteration 299:330 A frequently detected alteration in PDACs 299:339 A frequently detected alteration in PDACs is a truncated O-linked N-acetylgalactosamine (GalNAc) glycosylation with expression of the Tn antigen. 26021314 7 8 theme O-GalNAc 1154:1161 arg1 glycosylation 1163:1175 Altered O-GalNAc glycosylation 1146:1175 Altered O-GalNAc glycosylation 1146:1175 Altered O-GalNAc glycosylation was analyzed in human pancreatic cancer cell lines Panc-1 and L3.6pl using Western and Far-Western blot as well as immunocytochemical techniques. 26021314 6 9 from residue 1111:1117 arg1 glycoproteins 1131:1143 O-linked glycoproteins 1122:1143 O-linked glycoproteins 1122:1143 METHODS Forced expression of Tn antigen on O-glycosylated proteins in pancreatic cancer cells was induced by lentiviral-mediated knockdown of the COSMC chaperone, which prevented O-glycan elongation beyond the initial GalNAcα1- residue on O-linked glycoproteins. 26021314 3 10 theme profound 539:546 arg1 alterations 557:567 profound cellular alterations 539:567 profound cellular alterations 539:567 Changes in O-glycosylation affect posttranslationally modified O-GalNAc proteins resulting in profound cellular alterations. 26021314 12 11 theme antigen 2109:2115 arg1 expression 2117:2126 Tn antigen expression 2106:2126 Tn antigen expression 2106:2126 Proliferation was reduced (p < 0.001) in COSMC knockdown cells, whereas migration was increased (p < 0.001) and apoptosis was decreased (p = 0.03), highlighting the importance of Tn antigen expression on metastatic and anti-apoptotic behavior of PDAC derived cells. 26021314 15 12 from properties 2588:2597 arg1 cancer 2613:2618 pancreatic cancer 2602:2618 pancreatic cancer 2602:2618 CONCLUSION This study substantiates the influence of altered O-glycan (Tn/STn) expression on oncogenic properties in pancreatic cancer and identifies O-GalNAc modified Nucleolin as novel prognostic marker. 26021314 10 13 theme derived 1707:1713 arg1 specimens 1726:1734 patient derived PDAC tumor specimens 1699:1734 patient derived PDAC tumor specimens 1699:1734 Expression of Tn antigen bearing Nucleolin in patient derived PDAC tumor specimens was evaluated and correlated with clinicopathological data. 26021314 1 14 theme aggressive 178:187 arg1 malignancies 200:211 the most aggressive and lethal malignancies 169:211 the most aggressive and lethal malignancies in the world and despite great efforts in research types of treatment 169:281 BACKGROUND Human pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal malignancies in the world and despite great efforts in research types of treatment remain limited. 26021314 12 15 from importance 2092:2101 arg1 behavior 2161:2168 metastatic and anti-apoptotic behavior 2131:2168 metastatic and anti-apoptotic behavior of PDAC derived cells 2131:2190 Proliferation was reduced (p < 0.001) in COSMC knockdown cells, whereas migration was increased (p < 0.001) and apoptosis was decreased (p = 0.03), highlighting the importance of Tn antigen expression on metastatic and anti-apoptotic behavior of PDAC derived cells. 26021314 12 16 dep increased 2013:2021 arg1 p < 0.001 2024:2032 p < 0.001 2024:2032 p < 0.001 2024:2032 Proliferation was reduced (p < 0.001) in COSMC knockdown cells, whereas migration was increased (p < 0.001) and apoptosis was decreased (p = 0.03), highlighting the importance of Tn antigen expression on metastatic and anti-apoptotic behavior of PDAC derived cells. 26021314 2 17 theme detected 312:319 arg1 glycosylation 396:408 a truncated O-linked N-acetylgalactosamine (GalNAc) glycosylation 344:408 a truncated O-linked N-acetylgalactosamine (GalNAc) glycosylation with expression of the Tn antigen 344:442 A frequently detected alteration in PDACs is a truncated O-linked N-acetylgalactosamine (GalNAc) glycosylation with expression of the Tn antigen. 26021314 2 17 theme detected 312:319 arg1 alteration 321:330 A frequently detected alteration 299:330 A frequently detected alteration in PDACs 299:339 A frequently detected alteration in PDACs is a truncated O-linked N-acetylgalactosamine (GalNAc) glycosylation with expression of the Tn antigen. 26021314 1 18 theme lethal 193:198 arg1 malignancies 200:211 the most aggressive and lethal malignancies 169:211 the most aggressive and lethal malignancies in the world and despite great efforts in research types of treatment 169:281 BACKGROUND Human pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal malignancies in the world and despite great efforts in research types of treatment remain limited. 26021314 12 19 dep decreased 2053:2061 arg1 p = 0.03 2064:2071 p = 0.03 2064:2071 p = 0.03 2064:2071 Proliferation was reduced (p < 0.001) in COSMC knockdown cells, whereas migration was increased (p < 0.001) and apoptosis was decreased (p = 0.03), highlighting the importance of Tn antigen expression on metastatic and anti-apoptotic behavior of PDAC derived cells. 26021314 5 20 theme expression 709:718 arg1 role 690:693 the role 686:693 the role of Tn antigen expression in PDAC 686:726 Since the role of Tn antigen expression in PDAC is insufficiently understood we analyzed the impact of COSMC mediated Tn antigen expression in two human PDAC cell lines on cellular oncogenic properties. 26021314 13 21 theme modified 2230:2237 arg1 protein 2239:2245 O-GalNAc modified protein 2221:2245 O-GalNAc modified protein in COSMC deficient PDAC cell lines 2221:2280 Nucleolin was identified as O-GalNAc modified protein in COSMC deficient PDAC cell lines. 26021314 13 21 theme modified 2230:2237 arg1 Nucleolin 2193:2201 Nucleolin 2193:2201 Nucleolin 2193:2201 Nucleolin was identified as O-GalNAc modified protein in COSMC deficient PDAC cell lines. 26021314 3 22 theme cellular 548:555 arg1 alterations 557:567 profound cellular alterations 539:567 profound cellular alterations 539:567 Changes in O-glycosylation affect posttranslationally modified O-GalNAc proteins resulting in profound cellular alterations. 26021314 4 23 from % 652:652 arg1 lesions 671:677 its precursor lesions 657:677 its precursor lesions 657:677 Tn antigen is a tumor associated glycan detected in 75-90 % of PDACs and up to 67 % in its precursor lesions. 26021314 5 24 theme cell 838:841 arg1 lines 843:847 two human PDAC cell lines 823:847 two human PDAC cell lines 823:847 Since the role of Tn antigen expression in PDAC is insufficiently understood we analyzed the impact of COSMC mediated Tn antigen expression in two human PDAC cell lines on cellular oncogenic properties. 26021314 12 25 theme derived 2178:2184 arg1 cells 2186:2190 PDAC derived cells 2173:2190 PDAC derived cells 2173:2190 Proliferation was reduced (p < 0.001) in COSMC knockdown cells, whereas migration was increased (p < 0.001) and apoptosis was decreased (p = 0.03), highlighting the importance of Tn antigen expression on metastatic and anti-apoptotic behavior of PDAC derived cells. 26021314 10 26 theme tumor 1720:1724 arg1 specimens 1726:1734 patient derived PDAC tumor specimens 1699:1734 patient derived PDAC tumor specimens 1699:1734 Expression of Tn antigen bearing Nucleolin in patient derived PDAC tumor specimens was evaluated and correlated with clinicopathological data. 26021314 13 27 theme PDAC 2266:2269 arg1 lines 2276:2280 COSMC deficient PDAC cell lines 2250:2280 COSMC deficient PDAC cell lines 2250:2280 Nucleolin was identified as O-GalNAc modified protein in COSMC deficient PDAC cell lines. 26021314 7 28 theme cancer 1210:1215 arg1 lines 1222:1226 human pancreatic cancer cell lines Panc-1 and L3.6pl 1193:1244 human pancreatic cancer cell lines Panc-1 and L3.6pl 1193:1244 Altered O-GalNAc glycosylation was analyzed in human pancreatic cancer cell lines Panc-1 and L3.6pl using Western and Far-Western blot as well as immunocytochemical techniques. 26021314 7 28 theme cancer 1210:1215 arg1 L3.6pl 1239:1244 L3.6pl 1239:1244 L3.6pl 1239:1244 Altered O-GalNAc glycosylation was analyzed in human pancreatic cancer cell lines Panc-1 and L3.6pl using Western and Far-Western blot as well as immunocytochemical techniques. 26021314 7 28 theme cancer 1210:1215 arg1 Panc-1 1228:1233 Panc-1 1228:1233 Panc-1 1228:1233 Altered O-GalNAc glycosylation was analyzed in human pancreatic cancer cell lines Panc-1 and L3.6pl using Western and Far-Western blot as well as immunocytochemical techniques. 26021314 5 29 from lines 843:847 arg1 impact 773:778 the impact 769:778 the impact of COSMC mediated Tn antigen expression in two human PDAC cell lines on cellular oncogenic properties 769:880 Since the role of Tn antigen expression in PDAC is insufficiently understood we analyzed the impact of COSMC mediated Tn antigen expression in two human PDAC cell lines on cellular oncogenic properties. 26021314 6 30 theme pancreatic 953:962 arg1 cells 971:975 pancreatic cancer cells 953:975 pancreatic cancer cells 953:975 METHODS Forced expression of Tn antigen on O-glycosylated proteins in pancreatic cancer cells was induced by lentiviral-mediated knockdown of the COSMC chaperone, which prevented O-glycan elongation beyond the initial GalNAcα1- residue on O-linked glycoproteins. 26021314 12 31 theme cells 2186:2190 arg1 behavior 2161:2168 metastatic and anti-apoptotic behavior 2131:2168 metastatic and anti-apoptotic behavior of PDAC derived cells 2131:2190 Proliferation was reduced (p < 0.001) in COSMC knockdown cells, whereas migration was increased (p < 0.001) and apoptosis was decreased (p = 0.03), highlighting the importance of Tn antigen expression on metastatic and anti-apoptotic behavior of PDAC derived cells. 26021314 6 32 theme Tn 912:913 arg1 antigen 915:921 Tn antigen 912:921 Tn antigen 912:921 METHODS Forced expression of Tn antigen on O-glycosylated proteins in pancreatic cancer cells was induced by lentiviral-mediated knockdown of the COSMC chaperone, which prevented O-glycan elongation beyond the initial GalNAcα1- residue on O-linked glycoproteins. 26021314 1 33 from efforts 244:250 arg1 types 264:268 research types 255:268 research types of treatment 255:281 BACKGROUND Human pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal malignancies in the world and despite great efforts in research types of treatment remain limited. 26021314 5 34 from impact 773:778 arg1 lines 843:847 two human PDAC cell lines 823:847 two human PDAC cell lines 823:847 Since the role of Tn antigen expression in PDAC is insufficiently understood we analyzed the impact of COSMC mediated Tn antigen expression in two human PDAC cell lines on cellular oncogenic properties. 26021314 5 34 from impact 773:778 arg1 properties 871:880 cellular oncogenic properties 852:880 cellular oncogenic properties 852:880 Since the role of Tn antigen expression in PDAC is insufficiently understood we analyzed the impact of COSMC mediated Tn antigen expression in two human PDAC cell lines on cellular oncogenic properties. 26021314 1 35 from malignancies 200:211 arg1 world 220:224 the world 216:224 the world 216:224 BACKGROUND Human pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal malignancies in the world and despite great efforts in research types of treatment remain limited. 26021314 9 36 theme subsequent 1564:1573 arg1 analysis 1594:1601 subsequent mass spectrometric analysis 1564:1601 subsequent mass spectrometric analysis 1564:1601 Lectin based glycoprotein enrichment with subsequent mass spectrometric analysis identified new cancer O-GalNAc modified proteins. 26021314 8 37 theme COSMC 1364:1368 arg1 function 1370:1377 COSMC function 1364:1377 COSMC function 1364:1377 To assess the biological implications of COSMC function on oncogenic properties, cell viability assays, scratch assays combined with live cell imaging, migration and apoptosis assays were performed. 26021314 5 38 theme Tn 698:699 arg1 expression 709:718 Tn antigen expression 698:718 Tn antigen expression 698:718 Since the role of Tn antigen expression in PDAC is insufficiently understood we analyzed the impact of COSMC mediated Tn antigen expression in two human PDAC cell lines on cellular oncogenic properties. 26021314 15 39 theme pancreatic 2602:2611 arg1 cancer 2613:2618 pancreatic cancer 2602:2618 pancreatic cancer 2602:2618 CONCLUSION This study substantiates the influence of altered O-glycan (Tn/STn) expression on oncogenic properties in pancreatic cancer and identifies O-GalNAc modified Nucleolin as novel prognostic marker. 26021314 9 40 theme spectrometric 1580:1592 arg1 analysis 1594:1601 subsequent mass spectrometric analysis 1564:1601 subsequent mass spectrometric analysis 1564:1601 Lectin based glycoprotein enrichment with subsequent mass spectrometric analysis identified new cancer O-GalNAc modified proteins. 26021314 14 41 theme staining 2318:2325 arg1 studies 2347:2353 immunohistochemical staining and co-localization studies 2298:2353 immunohistochemical staining and co-localization studies of patient derived PDACs 2298:2378 Interestingly, immunohistochemical staining and co-localization studies of patient derived PDACs revealed poor survival for patients with strong co-localization of Tn antigen and Nucleolin (p = 0.037). 26021314 9 42 gly glycoprotein 1535:1546 arg1 glycoprotein 1535:1546 Lectin based glycoprotein enrichment 1522:1557 Lectin based glycoprotein enrichment with subsequent mass spectrometric analysis 1522:1601 Lectin based glycoprotein enrichment with subsequent mass spectrometric analysis identified new cancer O-GalNAc modified proteins. 26021314 14 43 theme Nucleolin 2462:2470 arg1 co-localization 2428:2442 strong co-localization 2421:2442 strong co-localization of Tn antigen and Nucleolin (p = 0.037) 2421:2482 Interestingly, immunohistochemical staining and co-localization studies of patient derived PDACs revealed poor survival for patients with strong co-localization of Tn antigen and Nucleolin (p = 0.037). 26021314 11 44 theme O-GalNAc 1849:1856 arg1 glycoproteins 1858:1870 various O-GalNAc glycoproteins 1841:1870 various O-GalNAc glycoproteins in COSMC deficient cell lines 1841:1900 RESULTS Tn antigen expression was induced on various O-GalNAc glycoproteins in COSMC deficient cell lines compared to the control. 26021314 5 45 theme human 827:831 arg1 lines 843:847 two human PDAC cell lines 823:847 two human PDAC cell lines 823:847 Since the role of Tn antigen expression in PDAC is insufficiently understood we analyzed the impact of COSMC mediated Tn antigen expression in two human PDAC cell lines on cellular oncogenic properties. 26021314 6 46 theme COSMC 1029:1033 arg1 chaperone 1035:1043 the COSMC chaperone 1025:1043 the COSMC chaperone 1025:1043 METHODS Forced expression of Tn antigen on O-glycosylated proteins in pancreatic cancer cells was induced by lentiviral-mediated knockdown of the COSMC chaperone, which prevented O-glycan elongation beyond the initial GalNAcα1- residue on O-linked glycoproteins. 26021314 6 47 gly glycoproteins 1131:1143 arg1 glycoproteins 1131:1143 O-linked glycoproteins 1122:1143 O-linked glycoproteins 1122:1143 METHODS Forced expression of Tn antigen on O-glycosylated proteins in pancreatic cancer cells was induced by lentiviral-mediated knockdown of the COSMC chaperone, which prevented O-glycan elongation beyond the initial GalNAcα1- residue on O-linked glycoproteins. 26021314 1 48 dep BACKGROUND 102:111 arg1 one 162:164 one 162:164 one 162:164 BACKGROUND Human pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal malignancies in the world and despite great efforts in research types of treatment remain limited. 26021314 1 48 dep BACKGROUND 102:111 arg1 malignancies 200:211 the most aggressive and lethal malignancies 169:211 the most aggressive and lethal malignancies in the world and despite great efforts in research types of treatment 169:281 BACKGROUND Human pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal malignancies in the world and despite great efforts in research types of treatment remain limited. 26021314 6 49 gly O-glycosylated 926:939 arg1 proteins 941:948 O-glycosylated proteins 926:948 O-glycosylated proteins in pancreatic cancer cells 926:975 METHODS Forced expression of Tn antigen on O-glycosylated proteins in pancreatic cancer cells was induced by lentiviral-mediated knockdown of the COSMC chaperone, which prevented O-glycan elongation beyond the initial GalNAcα1- residue on O-linked glycoproteins. 26021314 7 50 theme Far-Western 1264:1274 arg1 techniques 1311:1320 Western and Far-Western blot as well as immunocytochemical techniques 1252:1320 Western and Far-Western blot as well as immunocytochemical techniques 1252:1320 Altered O-GalNAc glycosylation was analyzed in human pancreatic cancer cell lines Panc-1 and L3.6pl using Western and Far-Western blot as well as immunocytochemical techniques. 26021314 9 51 theme cancer 1618:1623 arg1 proteins 1643:1650 new cancer O-GalNAc modified proteins 1614:1650 new cancer O-GalNAc modified proteins 1614:1650 Lectin based glycoprotein enrichment with subsequent mass spectrometric analysis identified new cancer O-GalNAc modified proteins. 26021314 2 52 from alteration 321:330 arg1 PDACs 335:339 PDACs 335:339 PDACs 335:339 A frequently detected alteration in PDACs is a truncated O-linked N-acetylgalactosamine (GalNAc) glycosylation with expression of the Tn antigen. 26021314 15 53 dep CONCLUSION 2485:2494 arg1 identifies 2624:2633 identifies 2624:2633 identifies O-GalNAc modified Nucleolin as novel prognostic marker 2624:2688 CONCLUSION This study substantiates the influence of altered O-glycan (Tn/STn) expression on oncogenic properties in pancreatic cancer and identifies O-GalNAc modified Nucleolin as novel prognostic marker. 26021314 15 53 dep CONCLUSION 2485:2494 arg1 substantiates 2507:2519 substantiates 2507:2519 substantiates the influence of altered O-glycan (Tn/STn) expression on oncogenic properties in pancreatic cancer 2507:2618 CONCLUSION This study substantiates the influence of altered O-glycan (Tn/STn) expression on oncogenic properties in pancreatic cancer and identifies O-GalNAc modified Nucleolin as novel prognostic marker. 26021314 7 54 dep lines 1222:1226 arg1 lines 1222:1226 human pancreatic cancer cell lines Panc-1 and L3.6pl 1193:1244 human pancreatic cancer cell lines Panc-1 and L3.6pl 1193:1244 Altered O-GalNAc glycosylation was analyzed in human pancreatic cancer cell lines Panc-1 and L3.6pl using Western and Far-Western blot as well as immunocytochemical techniques. 26021314 7 54 dep lines 1222:1226 arg1 L3.6pl 1239:1244 L3.6pl 1239:1244 L3.6pl 1239:1244 Altered O-GalNAc glycosylation was analyzed in human pancreatic cancer cell lines Panc-1 and L3.6pl using Western and Far-Western blot as well as immunocytochemical techniques. 26021314 7 54 dep lines 1222:1226 arg1 Panc-1 1228:1233 Panc-1 1228:1233 Panc-1 1228:1233 Altered O-GalNAc glycosylation was analyzed in human pancreatic cancer cell lines Panc-1 and L3.6pl using Western and Far-Western blot as well as immunocytochemical techniques. 26021314 8 55 theme cell 1404:1407 arg1 assays 1499:1504 migration and apoptosis assays 1475:1504 migration and apoptosis assays 1475:1504 To assess the biological implications of COSMC function on oncogenic properties, cell viability assays, scratch assays combined with live cell imaging, migration and apoptosis assays were performed. 26021314 8 55 theme cell 1404:1407 arg1 assays 1419:1424 cell viability assays 1404:1424 cell viability assays 1404:1424 To assess the biological implications of COSMC function on oncogenic properties, cell viability assays, scratch assays combined with live cell imaging, migration and apoptosis assays were performed. 26021314 8 55 theme cell 1404:1407 arg1 assays 1435:1440 scratch assays 1427:1440 scratch assays combined with live cell imaging 1427:1472 To assess the biological implications of COSMC function on oncogenic properties, cell viability assays, scratch assays combined with live cell imaging, migration and apoptosis assays were performed. 26021314 12 56 dep derived 2178:2184 arg1 PDAC 2173:2176 PDAC 2173:2176 PDAC 2173:2176 Proliferation was reduced (p < 0.001) in COSMC knockdown cells, whereas migration was increased (p < 0.001) and apoptosis was decreased (p = 0.03), highlighting the importance of Tn antigen expression on metastatic and anti-apoptotic behavior of PDAC derived cells. 26021314 11 57 theme deficient 1881:1889 arg1 lines 1896:1900 COSMC deficient cell lines 1875:1900 COSMC deficient cell lines 1875:1900 RESULTS Tn antigen expression was induced on various O-GalNAc glycoproteins in COSMC deficient cell lines compared to the control. 26021314 4 58 from % 628:628 arg1 lesions 671:677 its precursor lesions 657:677 its precursor lesions 657:677 Tn antigen is a tumor associated glycan detected in 75-90 % of PDACs and up to 67 % in its precursor lesions. 26021314 8 59 from implications 1348:1359 arg1 properties 1392:1401 oncogenic properties 1382:1401 oncogenic properties 1382:1401 To assess the biological implications of COSMC function on oncogenic properties, cell viability assays, scratch assays combined with live cell imaging, migration and apoptosis assays were performed. 26021314 9 60 theme modified 1634:1641 arg1 proteins 1643:1650 new cancer O-GalNAc modified proteins 1614:1650 new cancer O-GalNAc modified proteins 1614:1650 Lectin based glycoprotein enrichment with subsequent mass spectrometric analysis identified new cancer O-GalNAc modified proteins. 26021314 6 61 theme lentiviral-mediated 992:1010 arg1 knockdown 1012:1020 lentiviral-mediated knockdown 992:1020 lentiviral-mediated knockdown of the COSMC chaperone, which prevented O-glycan elongation beyond the initial GalNAcα1- residue on O-linked glycoproteins 992:1143 METHODS Forced expression of Tn antigen on O-glycosylated proteins in pancreatic cancer cells was induced by lentiviral-mediated knockdown of the COSMC chaperone, which prevented O-glycan elongation beyond the initial GalNAcα1- residue on O-linked glycoproteins. 26021314 15 62 from influence 2525:2533 arg1 properties 2588:2597 oncogenic properties 2578:2597 oncogenic properties in pancreatic cancer 2578:2618 CONCLUSION This study substantiates the influence of altered O-glycan (Tn/STn) expression on oncogenic properties in pancreatic cancer and identifies O-GalNAc modified Nucleolin as novel prognostic marker. 26021314 14 63 theme strong 2421:2426 arg1 co-localization 2428:2442 strong co-localization 2421:2442 strong co-localization of Tn antigen and Nucleolin (p = 0.037) 2421:2482 Interestingly, immunohistochemical staining and co-localization studies of patient derived PDACs revealed poor survival for patients with strong co-localization of Tn antigen and Nucleolin (p = 0.037). 26021314 9 64 theme Lectin 1522:1527 arg1 enrichment 1548:1557 Lectin based glycoprotein enrichment 1522:1557 Lectin based glycoprotein enrichment with subsequent mass spectrometric analysis 1522:1601 Lectin based glycoprotein enrichment with subsequent mass spectrometric analysis identified new cancer O-GalNAc modified proteins. 26021314 5 65 from expression 809:818 arg1 lines 843:847 two human PDAC cell lines 823:847 two human PDAC cell lines 823:847 Since the role of Tn antigen expression in PDAC is insufficiently understood we analyzed the impact of COSMC mediated Tn antigen expression in two human PDAC cell lines on cellular oncogenic properties. 26021314 7 66 theme human 1193:1197 arg1 lines 1222:1226 human pancreatic cancer cell lines Panc-1 and L3.6pl 1193:1244 human pancreatic cancer cell lines Panc-1 and L3.6pl 1193:1244 Altered O-GalNAc glycosylation was analyzed in human pancreatic cancer cell lines Panc-1 and L3.6pl using Western and Far-Western blot as well as immunocytochemical techniques. 26021314 7 66 theme human 1193:1197 arg1 L3.6pl 1239:1244 L3.6pl 1239:1244 L3.6pl 1239:1244 Altered O-GalNAc glycosylation was analyzed in human pancreatic cancer cell lines Panc-1 and L3.6pl using Western and Far-Western blot as well as immunocytochemical techniques. 26021314 7 66 theme human 1193:1197 arg1 Panc-1 1228:1233 Panc-1 1228:1233 Panc-1 1228:1233 Altered O-GalNAc glycosylation was analyzed in human pancreatic cancer cell lines Panc-1 and L3.6pl using Western and Far-Western blot as well as immunocytochemical techniques. 26021314 15 67 theme novel 2666:2670 arg1 marker 2683:2688 novel prognostic marker 2666:2688 novel prognostic marker 2666:2688 CONCLUSION This study substantiates the influence of altered O-glycan (Tn/STn) expression on oncogenic properties in pancreatic cancer and identifies O-GalNAc modified Nucleolin as novel prognostic marker. 26021314 6 68 theme GalNAcα1- 1101:1109 arg1 residue 1111:1117 the initial GalNAcα1- residue 1089:1117 the initial GalNAcα1- residue on O-linked glycoproteins 1089:1143 METHODS Forced expression of Tn antigen on O-glycosylated proteins in pancreatic cancer cells was induced by lentiviral-mediated knockdown of the COSMC chaperone, which prevented O-glycan elongation beyond the initial GalNAcα1- residue on O-linked glycoproteins. 26021314 0 69 theme pancreatic 83:92 arg1 cancer 94:99 pancreatic cancer 83:99 pancreatic cancer 83:99 COSMC knockdown mediated aberrant O-glycosylation promotes oncogenic properties in pancreatic cancer. 26021314 8 70 theme scratch 1427:1433 arg1 assays 1419:1424 cell viability assays 1404:1424 cell viability assays 1404:1424 To assess the biological implications of COSMC function on oncogenic properties, cell viability assays, scratch assays combined with live cell imaging, migration and apoptosis assays were performed. 26021314 8 70 theme scratch 1427:1433 arg1 assays 1435:1440 scratch assays 1427:1440 scratch assays combined with live cell imaging 1427:1472 To assess the biological implications of COSMC function on oncogenic properties, cell viability assays, scratch assays combined with live cell imaging, migration and apoptosis assays were performed. 26021314 0 71 theme COSMC 0:4 arg1 knockdown 6:14 COSMC knockdown 0:14 COSMC knockdown 0:14 COSMC knockdown mediated aberrant O-glycosylation promotes oncogenic properties in pancreatic cancer. 26021314 1 72 theme treatment 273:281 arg1 types 264:268 research types 255:268 research types of treatment 255:281 BACKGROUND Human pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal malignancies in the world and despite great efforts in research types of treatment remain limited. 26021314 1 73 theme Human 113:117 arg1 PDAC 153:156 PDAC 153:156 PDAC 153:156 BACKGROUND Human pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal malignancies in the world and despite great efforts in research types of treatment remain limited. 26021314 1 73 theme Human 113:117 arg1 adenocarcinoma 137:150 Human pancreatic ductal adenocarcinoma 113:150 Human pancreatic ductal adenocarcinoma (PDAC) 113:157 BACKGROUND Human pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal malignancies in the world and despite great efforts in research types of treatment remain limited. 26021314 4 74 theme tumor 586:590 arg1 glycan 603:608 a tumor associated glycan 584:608 a tumor associated glycan detected in 75-90 % of PDACs and up to 67 % in its precursor lesions 584:677 Tn antigen is a tumor associated glycan detected in 75-90 % of PDACs and up to 67 % in its precursor lesions. 26021314 4 74 theme tumor 586:590 arg1 antigen 573:579 Tn antigen 570:579 Tn antigen 570:579 Tn antigen is a tumor associated glycan detected in 75-90 % of PDACs and up to 67 % in its precursor lesions. 26021314 11 75 gly glycoproteins 1858:1870 arg1 glycoproteins 1858:1870 various O-GalNAc glycoproteins 1841:1870 various O-GalNAc glycoproteins in COSMC deficient cell lines 1841:1900 RESULTS Tn antigen expression was induced on various O-GalNAc glycoproteins in COSMC deficient cell lines compared to the control. 26021314 12 76 dep reduced 1945:1951 arg1 p < 0.001 1954:1962 p < 0.001 1954:1962 p < 0.001 1954:1962 Proliferation was reduced (p < 0.001) in COSMC knockdown cells, whereas migration was increased (p < 0.001) and apoptosis was decreased (p = 0.03), highlighting the importance of Tn antigen expression on metastatic and anti-apoptotic behavior of PDAC derived cells. 26021314 12 76 dep reduced 1945:1951 arg1 whereas 1991:1997 whereas 1991:1997 whereas 1991:1997 Proliferation was reduced (p < 0.001) in COSMC knockdown cells, whereas migration was increased (p < 0.001) and apoptosis was decreased (p = 0.03), highlighting the importance of Tn antigen expression on metastatic and anti-apoptotic behavior of PDAC derived cells. 26021314 2 77 theme Tn 433:434 arg1 antigen 436:442 the Tn antigen 429:442 the Tn antigen 429:442 A frequently detected alteration in PDACs is a truncated O-linked N-acetylgalactosamine (GalNAc) glycosylation with expression of the Tn antigen. 26021314 7 78 theme cell 1217:1220 arg1 lines 1222:1226 human pancreatic cancer cell lines Panc-1 and L3.6pl 1193:1244 human pancreatic cancer cell lines Panc-1 and L3.6pl 1193:1244 Altered O-GalNAc glycosylation was analyzed in human pancreatic cancer cell lines Panc-1 and L3.6pl using Western and Far-Western blot as well as immunocytochemical techniques. 26021314 7 78 theme cell 1217:1220 arg1 L3.6pl 1239:1244 L3.6pl 1239:1244 L3.6pl 1239:1244 Altered O-GalNAc glycosylation was analyzed in human pancreatic cancer cell lines Panc-1 and L3.6pl using Western and Far-Western blot as well as immunocytochemical techniques. 26021314 7 78 theme cell 1217:1220 arg1 Panc-1 1228:1233 Panc-1 1228:1233 Panc-1 1228:1233 Altered O-GalNAc glycosylation was analyzed in human pancreatic cancer cell lines Panc-1 and L3.6pl using Western and Far-Western blot as well as immunocytochemical techniques. 26021314 12 79 theme knockdown 1974:1982 arg1 cells 1984:1988 COSMC knockdown cells 1968:1988 COSMC knockdown cells 1968:1988 Proliferation was reduced (p < 0.001) in COSMC knockdown cells, whereas migration was increased (p < 0.001) and apoptosis was decreased (p = 0.03), highlighting the importance of Tn antigen expression on metastatic and anti-apoptotic behavior of PDAC derived cells. 26021314 1 80 theme ductal 130:135 arg1 PDAC 153:156 PDAC 153:156 PDAC 153:156 BACKGROUND Human pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal malignancies in the world and despite great efforts in research types of treatment remain limited. 26021314 1 80 theme ductal 130:135 arg1 adenocarcinoma 137:150 Human pancreatic ductal adenocarcinoma 113:150 Human pancreatic ductal adenocarcinoma (PDAC) 113:157 BACKGROUND Human pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal malignancies in the world and despite great efforts in research types of treatment remain limited. 26021314 8 81 theme live 1456:1459 arg1 imaging 1466:1472 live cell imaging 1456:1472 live cell imaging 1456:1472 To assess the biological implications of COSMC function on oncogenic properties, cell viability assays, scratch assays combined with live cell imaging, migration and apoptosis assays were performed. 26021314 10 82 theme clinicopathological 1770:1788 arg1 data 1790:1793 clinicopathological data 1770:1793 clinicopathological data 1770:1793 Expression of Tn antigen bearing Nucleolin in patient derived PDAC tumor specimens was evaluated and correlated with clinicopathological data. 26021314 5 83 theme mediated 789:796 arg1 expression 809:818 COSMC mediated Tn antigen expression 783:818 COSMC mediated Tn antigen expression in two human PDAC cell lines 783:847 Since the role of Tn antigen expression in PDAC is insufficiently understood we analyzed the impact of COSMC mediated Tn antigen expression in two human PDAC cell lines on cellular oncogenic properties. 26021314 7 84 theme pancreatic 1199:1208 arg1 lines 1222:1226 human pancreatic cancer cell lines Panc-1 and L3.6pl 1193:1244 human pancreatic cancer cell lines Panc-1 and L3.6pl 1193:1244 Altered O-GalNAc glycosylation was analyzed in human pancreatic cancer cell lines Panc-1 and L3.6pl using Western and Far-Western blot as well as immunocytochemical techniques. 26021314 7 84 theme pancreatic 1199:1208 arg1 L3.6pl 1239:1244 L3.6pl 1239:1244 L3.6pl 1239:1244 Altered O-GalNAc glycosylation was analyzed in human pancreatic cancer cell lines Panc-1 and L3.6pl using Western and Far-Western blot as well as immunocytochemical techniques. 26021314 7 84 theme pancreatic 1199:1208 arg1 Panc-1 1228:1233 Panc-1 1228:1233 Panc-1 1228:1233 Altered O-GalNAc glycosylation was analyzed in human pancreatic cancer cell lines Panc-1 and L3.6pl using Western and Far-Western blot as well as immunocytochemical techniques. 26021314 12 85 theme Tn 2106:2107 arg1 expression 2117:2126 Tn antigen expression 2106:2126 Tn antigen expression 2106:2126 Proliferation was reduced (p < 0.001) in COSMC knockdown cells, whereas migration was increased (p < 0.001) and apoptosis was decreased (p = 0.03), highlighting the importance of Tn antigen expression on metastatic and anti-apoptotic behavior of PDAC derived cells. 26021314 4 86 theme Tn 570:571 arg1 glycan 603:608 a tumor associated glycan 584:608 a tumor associated glycan detected in 75-90 % of PDACs and up to 67 % in its precursor lesions 584:677 Tn antigen is a tumor associated glycan detected in 75-90 % of PDACs and up to 67 % in its precursor lesions. 26021314 4 86 theme Tn 570:571 arg1 antigen 573:579 Tn antigen 570:579 Tn antigen 570:579 Tn antigen is a tumor associated glycan detected in 75-90 % of PDACs and up to 67 % in its precursor lesions. 26021314 11 87 theme Tn 1804:1805 arg1 expression 1815:1824 Tn antigen expression 1804:1824 Tn antigen expression 1804:1824 RESULTS Tn antigen expression was induced on various O-GalNAc glycoproteins in COSMC deficient cell lines compared to the control. 26021314 5 88 theme antigen 801:807 arg1 expression 809:818 COSMC mediated Tn antigen expression 783:818 COSMC mediated Tn antigen expression in two human PDAC cell lines 783:847 Since the role of Tn antigen expression in PDAC is insufficiently understood we analyzed the impact of COSMC mediated Tn antigen expression in two human PDAC cell lines on cellular oncogenic properties. 26021314 4 89 dep 67 649:650 arg1 to 646:647 to 646:647 to 646:647 Tn antigen is a tumor associated glycan detected in 75-90 % of PDACs and up to 67 % in its precursor lesions. 26021314 11 90 theme various 1841:1847 arg1 glycoproteins 1858:1870 various O-GalNAc glycoproteins 1841:1870 various O-GalNAc glycoproteins in COSMC deficient cell lines 1841:1900 RESULTS Tn antigen expression was induced on various O-GalNAc glycoproteins in COSMC deficient cell lines compared to the control. 26021314 8 91 theme migration 1475:1483 arg1 assays 1499:1504 migration and apoptosis assays 1475:1504 migration and apoptosis assays 1475:1504 To assess the biological implications of COSMC function on oncogenic properties, cell viability assays, scratch assays combined with live cell imaging, migration and apoptosis assays were performed. 26021314 8 91 theme migration 1475:1483 arg1 assays 1419:1424 cell viability assays 1404:1424 cell viability assays 1404:1424 To assess the biological implications of COSMC function on oncogenic properties, cell viability assays, scratch assays combined with live cell imaging, migration and apoptosis assays were performed. 26021314 3 92 theme O-GalNAc 508:515 arg1 proteins 517:524 posttranslationally modified O-GalNAc proteins 479:524 posttranslationally modified O-GalNAc proteins resulting in profound cellular alterations 479:567 Changes in O-glycosylation affect posttranslationally modified O-GalNAc proteins resulting in profound cellular alterations. 26021314 11 93 dep RESULTS 1796:1802 arg1 induced 1830:1836 induced 1830:1836 was induced on various O-GalNAc glycoproteins in COSMC deficient cell lines compared to the control 1826:1924 RESULTS Tn antigen expression was induced on various O-GalNAc glycoproteins in COSMC deficient cell lines compared to the control. 26021314 12 94 theme anti-apoptotic 2146:2159 arg1 behavior 2161:2168 metastatic and anti-apoptotic behavior 2131:2168 metastatic and anti-apoptotic behavior of PDAC derived cells 2131:2190 Proliferation was reduced (p < 0.001) in COSMC knockdown cells, whereas migration was increased (p < 0.001) and apoptosis was decreased (p = 0.03), highlighting the importance of Tn antigen expression on metastatic and anti-apoptotic behavior of PDAC derived cells. 26021314 4 95 theme PDACs 633:637 arg1 % 628:628 75-90 % 622:628 75-90 % of PDACs 622:637 Tn antigen is a tumor associated glycan detected in 75-90 % of PDACs and up to 67 % in its precursor lesions. 26021314 4 95 theme PDACs 633:637 arg1 % 652:652 up to 67 % 643:652 up to 67 % in its precursor lesions 643:677 Tn antigen is a tumor associated glycan detected in 75-90 % of PDACs and up to 67 % in its precursor lesions. 26021314 4 95 theme PDACs 633:637 arg1 PDACs 633:637 PDACs 633:637 PDACs 633:637 Tn antigen is a tumor associated glycan detected in 75-90 % of PDACs and up to 67 % in its precursor lesions. 26021314 14 96 theme PDACs 2374:2378 arg1 studies 2347:2353 immunohistochemical staining and co-localization studies 2298:2353 immunohistochemical staining and co-localization studies of patient derived PDACs 2298:2378 Interestingly, immunohistochemical staining and co-localization studies of patient derived PDACs revealed poor survival for patients with strong co-localization of Tn antigen and Nucleolin (p = 0.037). 26021314 8 97 theme apoptosis 1489:1497 arg1 assays 1499:1504 migration and apoptosis assays 1475:1504 migration and apoptosis assays 1475:1504 To assess the biological implications of COSMC function on oncogenic properties, cell viability assays, scratch assays combined with live cell imaging, migration and apoptosis assays were performed. 26021314 8 97 theme apoptosis 1489:1497 arg1 assays 1419:1424 cell viability assays 1404:1424 cell viability assays 1404:1424 To assess the biological implications of COSMC function on oncogenic properties, cell viability assays, scratch assays combined with live cell imaging, migration and apoptosis assays were performed. 26021314 5 98 theme oncogenic 861:869 arg1 properties 871:880 cellular oncogenic properties 852:880 cellular oncogenic properties 852:880 Since the role of Tn antigen expression in PDAC is insufficiently understood we analyzed the impact of COSMC mediated Tn antigen expression in two human PDAC cell lines on cellular oncogenic properties. 26021314 1 99 theme great 238:242 arg1 efforts 244:250 great efforts 238:250 great efforts in research types of treatment 238:281 BACKGROUND Human pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal malignancies in the world and despite great efforts in research types of treatment remain limited. 26021314 12 100 theme expression 2117:2126 arg1 importance 2092:2101 the importance 2088:2101 the importance of Tn antigen expression on metastatic and anti-apoptotic behavior of PDAC derived cells 2088:2190 Proliferation was reduced (p < 0.001) in COSMC knockdown cells, whereas migration was increased (p < 0.001) and apoptosis was decreased (p = 0.03), highlighting the importance of Tn antigen expression on metastatic and anti-apoptotic behavior of PDAC derived cells. 26021314 6 101 theme O-glycosylated 926:939 arg1 proteins 941:948 O-glycosylated proteins 926:948 O-glycosylated proteins in pancreatic cancer cells 926:975 METHODS Forced expression of Tn antigen on O-glycosylated proteins in pancreatic cancer cells was induced by lentiviral-mediated knockdown of the COSMC chaperone, which prevented O-glycan elongation beyond the initial GalNAcα1- residue on O-linked glycoproteins. 26021314 6 102 dep expression 898:907 arg1 proteins 941:948 O-glycosylated proteins 926:948 O-glycosylated proteins in pancreatic cancer cells 926:975 METHODS Forced expression of Tn antigen on O-glycosylated proteins in pancreatic cancer cells was induced by lentiviral-mediated knockdown of the COSMC chaperone, which prevented O-glycan elongation beyond the initial GalNAcα1- residue on O-linked glycoproteins. 26021314 2 103 theme O-linked 356:363 arg1 glycosylation 396:408 a truncated O-linked N-acetylgalactosamine (GalNAc) glycosylation 344:408 a truncated O-linked N-acetylgalactosamine (GalNAc) glycosylation with expression of the Tn antigen 344:442 A frequently detected alteration in PDACs is a truncated O-linked N-acetylgalactosamine (GalNAc) glycosylation with expression of the Tn antigen. 26021314 2 103 theme O-linked 356:363 arg1 alteration 321:330 A frequently detected alteration 299:330 A frequently detected alteration in PDACs 299:339 A frequently detected alteration in PDACs is a truncated O-linked N-acetylgalactosamine (GalNAc) glycosylation with expression of the Tn antigen. 26021314 13 104 theme deficient 2256:2264 arg1 lines 2276:2280 COSMC deficient PDAC cell lines 2250:2280 COSMC deficient PDAC cell lines 2250:2280 Nucleolin was identified as O-GalNAc modified protein in COSMC deficient PDAC cell lines. 26021314 12 105 theme metastatic 2131:2140 arg1 behavior 2161:2168 metastatic and anti-apoptotic behavior 2131:2168 metastatic and anti-apoptotic behavior of PDAC derived cells 2131:2190 Proliferation was reduced (p < 0.001) in COSMC knockdown cells, whereas migration was increased (p < 0.001) and apoptosis was decreased (p = 0.03), highlighting the importance of Tn antigen expression on metastatic and anti-apoptotic behavior of PDAC derived cells. 26021314 6 106 theme antigen 915:921 arg1 expression 898:907 Forced expression 891:907 Forced expression of Tn antigen 891:921 METHODS Forced expression of Tn antigen on O-glycosylated proteins in pancreatic cancer cells was induced by lentiviral-mediated knockdown of the COSMC chaperone, which prevented O-glycan elongation beyond the initial GalNAcα1- residue on O-linked glycoproteins. 26021314 10 107 theme antigen 1670:1676 arg1 Expression 1653:1662 Expression 1653:1662 Expression of Tn antigen bearing Nucleolin in patient derived PDAC tumor specimens 1653:1734 Expression of Tn antigen bearing Nucleolin in patient derived PDAC tumor specimens was evaluated and correlated with clinicopathological data. 26021314 7 108 theme Altered 1146:1152 arg1 glycosylation 1163:1175 Altered O-GalNAc glycosylation 1146:1175 Altered O-GalNAc glycosylation 1146:1175 Altered O-GalNAc glycosylation was analyzed in human pancreatic cancer cell lines Panc-1 and L3.6pl using Western and Far-Western blot as well as immunocytochemical techniques. 26021314 13 109 theme cell 2271:2274 arg1 lines 2276:2280 COSMC deficient PDAC cell lines 2250:2280 COSMC deficient PDAC cell lines 2250:2280 Nucleolin was identified as O-GalNAc modified protein in COSMC deficient PDAC cell lines. 26021314 14 110 theme antigen 2450:2456 arg1 co-localization 2428:2442 strong co-localization 2421:2442 strong co-localization of Tn antigen and Nucleolin (p = 0.037) 2421:2482 Interestingly, immunohistochemical staining and co-localization studies of patient derived PDACs revealed poor survival for patients with strong co-localization of Tn antigen and Nucleolin (p = 0.037). 26021314 5 111 theme cellular 852:859 arg1 properties 871:880 cellular oncogenic properties 852:880 cellular oncogenic properties 852:880 Since the role of Tn antigen expression in PDAC is insufficiently understood we analyzed the impact of COSMC mediated Tn antigen expression in two human PDAC cell lines on cellular oncogenic properties. 26021314 0 112 theme oncogenic 59:67 arg1 properties 69:78 oncogenic properties 59:78 oncogenic properties 59:78 COSMC knockdown mediated aberrant O-glycosylation promotes oncogenic properties in pancreatic cancer. 26021314 6 113 theme Forced 891:896 arg1 expression 898:907 Forced expression 891:907 Forced expression of Tn antigen 891:921 METHODS Forced expression of Tn antigen on O-glycosylated proteins in pancreatic cancer cells was induced by lentiviral-mediated knockdown of the COSMC chaperone, which prevented O-glycan elongation beyond the initial GalNAcα1- residue on O-linked glycoproteins. 26021314 14 114 with patients 2407:2414 arg1 co-localization 2428:2442 strong co-localization 2421:2442 strong co-localization of Tn antigen and Nucleolin (p = 0.037) 2421:2482 Interestingly, immunohistochemical staining and co-localization studies of patient derived PDACs revealed poor survival for patients with strong co-localization of Tn antigen and Nucleolin (p = 0.037). 26021314 4 115 theme precursor 661:669 arg1 lesions 671:677 its precursor lesions 657:677 its precursor lesions 657:677 Tn antigen is a tumor associated glycan detected in 75-90 % of PDACs and up to 67 % in its precursor lesions. 26021314 14 116 theme immunohistochemical 2298:2316 arg1 staining 2318:2325 immunohistochemical staining 2298:2325 immunohistochemical staining 2298:2325 Interestingly, immunohistochemical staining and co-localization studies of patient derived PDACs revealed poor survival for patients with strong co-localization of Tn antigen and Nucleolin (p = 0.037). 26021314 10 117 link derived 1707:1713 arg1 specimens 1726:1734 patient derived PDAC tumor specimens 1699:1734 patient derived PDAC tumor specimens 1699:1734 Expression of Tn antigen bearing Nucleolin in patient derived PDAC tumor specimens was evaluated and correlated with clinicopathological data. 26021314 5 118 theme antigen 701:707 arg1 expression 709:718 Tn antigen expression 698:718 Tn antigen expression 698:718 Since the role of Tn antigen expression in PDAC is insufficiently understood we analyzed the impact of COSMC mediated Tn antigen expression in two human PDAC cell lines on cellular oncogenic properties. 26021314 0 119 dep O-glycosylation 34:48 arg1 promotes 50:57 promotes 50:57 promotes oncogenic properties in pancreatic cancer 50:99 COSMC knockdown mediated aberrant O-glycosylation promotes oncogenic properties in pancreatic cancer. 26021314 14 120 theme co-localization 2331:2345 arg1 studies 2347:2353 immunohistochemical staining and co-localization studies 2298:2353 immunohistochemical staining and co-localization studies of patient derived PDACs 2298:2378 Interestingly, immunohistochemical staining and co-localization studies of patient derived PDACs revealed poor survival for patients with strong co-localization of Tn antigen and Nucleolin (p = 0.037). 26021314 5 121 theme PDAC 833:836 arg1 lines 843:847 two human PDAC cell lines 823:847 two human PDAC cell lines 823:847 Since the role of Tn antigen expression in PDAC is insufficiently understood we analyzed the impact of COSMC mediated Tn antigen expression in two human PDAC cell lines on cellular oncogenic properties. 26021314 7 122 gly glycosylation 1163:1175 arg1 lines 1222:1226 human pancreatic cancer cell lines Panc-1 and L3.6pl 1193:1244 human pancreatic cancer cell lines Panc-1 and L3.6pl 1193:1244 Altered O-GalNAc glycosylation was analyzed in human pancreatic cancer cell lines Panc-1 and L3.6pl using Western and Far-Western blot as well as immunocytochemical techniques. 26021314 7 122 gly glycosylation 1163:1175 arg1 L3.6pl 1239:1244 L3.6pl 1239:1244 L3.6pl 1239:1244 Altered O-GalNAc glycosylation was analyzed in human pancreatic cancer cell lines Panc-1 and L3.6pl using Western and Far-Western blot as well as immunocytochemical techniques. 26021314 7 122 gly glycosylation 1163:1175 arg1 Panc-1 1228:1233 Panc-1 1228:1233 Panc-1 1228:1233 Altered O-GalNAc glycosylation was analyzed in human pancreatic cancer cell lines Panc-1 and L3.6pl using Western and Far-Western blot as well as immunocytochemical techniques. 26021314 9 123 theme glycoprotein 1535:1546 arg1 enrichment 1548:1557 Lectin based glycoprotein enrichment 1522:1557 Lectin based glycoprotein enrichment with subsequent mass spectrometric analysis 1522:1601 Lectin based glycoprotein enrichment with subsequent mass spectrometric analysis identified new cancer O-GalNAc modified proteins. 26021314 6 124 theme cancer 964:969 arg1 cells 971:975 pancreatic cancer cells 953:975 pancreatic cancer cells 953:975 METHODS Forced expression of Tn antigen on O-glycosylated proteins in pancreatic cancer cells was induced by lentiviral-mediated knockdown of the COSMC chaperone, which prevented O-glycan elongation beyond the initial GalNAcα1- residue on O-linked glycoproteins. 26021314 10 125 theme PDAC 1715:1718 arg1 specimens 1726:1734 patient derived PDAC tumor specimens 1699:1734 patient derived PDAC tumor specimens 1699:1734 Expression of Tn antigen bearing Nucleolin in patient derived PDAC tumor specimens was evaluated and correlated with clinicopathological data. 26021314 13 126 theme COSMC 2250:2254 arg1 lines 2276:2280 COSMC deficient PDAC cell lines 2250:2280 COSMC deficient PDAC cell lines 2250:2280 Nucleolin was identified as O-GalNAc modified protein in COSMC deficient PDAC cell lines. 26021314 15 127 theme modified 2644:2651 arg1 Nucleolin 2653:2661 O-GalNAc modified Nucleolin 2635:2661 O-GalNAc modified Nucleolin 2635:2661 CONCLUSION This study substantiates the influence of altered O-glycan (Tn/STn) expression on oncogenic properties in pancreatic cancer and identifies O-GalNAc modified Nucleolin as novel prognostic marker. 26021314 11 128 from glycoproteins 1858:1870 arg1 lines 1896:1900 COSMC deficient cell lines 1875:1900 COSMC deficient cell lines 1875:1900 RESULTS Tn antigen expression was induced on various O-GalNAc glycoproteins in COSMC deficient cell lines compared to the control. 26021314 8 129 theme biological 1337:1346 arg1 implications 1348:1359 the biological implications 1333:1359 the biological implications of COSMC function on oncogenic properties 1333:1401 To assess the biological implications of COSMC function on oncogenic properties, cell viability assays, scratch assays combined with live cell imaging, migration and apoptosis assays were performed. 26021314 9 130 theme mass 1575:1578 arg1 analysis 1594:1601 subsequent mass spectrometric analysis 1564:1601 subsequent mass spectrometric analysis 1564:1601 Lectin based glycoprotein enrichment with subsequent mass spectrometric analysis identified new cancer O-GalNAc modified proteins. 26021314 11 131 theme COSMC 1875:1879 arg1 lines 1896:1900 COSMC deficient cell lines 1875:1900 COSMC deficient cell lines 1875:1900 RESULTS Tn antigen expression was induced on various O-GalNAc glycoproteins in COSMC deficient cell lines compared to the control. 26021314 7 132 theme blot 1276:1279 arg1 techniques 1311:1320 Western and Far-Western blot as well as immunocytochemical techniques 1252:1320 Western and Far-Western blot as well as immunocytochemical techniques 1252:1320 Altered O-GalNAc glycosylation was analyzed in human pancreatic cancer cell lines Panc-1 and L3.6pl using Western and Far-Western blot as well as immunocytochemical techniques. 26021314 13 133 theme O-GalNAc 2221:2228 arg1 protein 2239:2245 O-GalNAc modified protein 2221:2245 O-GalNAc modified protein in COSMC deficient PDAC cell lines 2221:2280 Nucleolin was identified as O-GalNAc modified protein in COSMC deficient PDAC cell lines. 26021314 13 133 theme O-GalNAc 2221:2228 arg1 Nucleolin 2193:2201 Nucleolin 2193:2201 Nucleolin 2193:2201 Nucleolin was identified as O-GalNAc modified protein in COSMC deficient PDAC cell lines. 26021314 1 134 theme malignancies 200:211 arg1 one 162:164 one 162:164 one 162:164 BACKGROUND Human pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal malignancies in the world and despite great efforts in research types of treatment remain limited. 26021314 1 134 theme malignancies 200:211 arg1 malignancies 200:211 the most aggressive and lethal malignancies 169:211 the most aggressive and lethal malignancies in the world and despite great efforts in research types of treatment 169:281 BACKGROUND Human pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal malignancies in the world and despite great efforts in research types of treatment remain limited. 26021314 6 135 theme chaperone 1035:1043 arg1 knockdown 1012:1020 lentiviral-mediated knockdown 992:1020 lentiviral-mediated knockdown of the COSMC chaperone, which prevented O-glycan elongation beyond the initial GalNAcα1- residue on O-linked glycoproteins 992:1143 METHODS Forced expression of Tn antigen on O-glycosylated proteins in pancreatic cancer cells was induced by lentiviral-mediated knockdown of the COSMC chaperone, which prevented O-glycan elongation beyond the initial GalNAcα1- residue on O-linked glycoproteins. 26021314 8 136 theme function 1370:1377 arg1 implications 1348:1359 the biological implications 1333:1359 the biological implications of COSMC function on oncogenic properties 1333:1401 To assess the biological implications of COSMC function on oncogenic properties, cell viability assays, scratch assays combined with live cell imaging, migration and apoptosis assays were performed. 26021314 7 137 theme Western 1252:1258 arg1 techniques 1311:1320 Western and Far-Western blot as well as immunocytochemical techniques 1252:1320 Western and Far-Western blot as well as immunocytochemical techniques 1252:1320 Altered O-GalNAc glycosylation was analyzed in human pancreatic cancer cell lines Panc-1 and L3.6pl using Western and Far-Western blot as well as immunocytochemical techniques. 26021314 15 138 theme oncogenic 2578:2586 arg1 properties 2588:2597 oncogenic properties 2578:2597 oncogenic properties in pancreatic cancer 2578:2618 CONCLUSION This study substantiates the influence of altered O-glycan (Tn/STn) expression on oncogenic properties in pancreatic cancer and identifies O-GalNAc modified Nucleolin as novel prognostic marker. 26021314 9 139 theme new 1614:1616 arg1 proteins 1643:1650 new cancer O-GalNAc modified proteins 1614:1650 new cancer O-GalNAc modified proteins 1614:1650 Lectin based glycoprotein enrichment with subsequent mass spectrometric analysis identified new cancer O-GalNAc modified proteins. 26021314 8 140 theme oncogenic 1382:1390 arg1 properties 1392:1401 oncogenic properties 1382:1401 oncogenic properties 1382:1401 To assess the biological implications of COSMC function on oncogenic properties, cell viability assays, scratch assays combined with live cell imaging, migration and apoptosis assays were performed. 26021314 14 141 theme Tn 2447:2448 arg1 antigen 2450:2456 Tn antigen 2447:2456 Tn antigen 2447:2456 Interestingly, immunohistochemical staining and co-localization studies of patient derived PDACs revealed poor survival for patients with strong co-localization of Tn antigen and Nucleolin (p = 0.037). 26021314 15 142 theme expression 2564:2573 arg1 influence 2525:2533 the influence 2521:2533 the influence of altered O-glycan (Tn/STn) expression on oncogenic properties in pancreatic cancer 2521:2618 CONCLUSION This study substantiates the influence of altered O-glycan (Tn/STn) expression on oncogenic properties in pancreatic cancer and identifies O-GalNAc modified Nucleolin as novel prognostic marker. 26021314 9 143 theme O-GalNAc 1625:1632 arg1 proteins 1643:1650 new cancer O-GalNAc modified proteins 1614:1650 new cancer O-GalNAc modified proteins 1614:1650 Lectin based glycoprotein enrichment with subsequent mass spectrometric analysis identified new cancer O-GalNAc modified proteins. 26021314 11 144 theme cell 1891:1894 arg1 lines 1896:1900 COSMC deficient cell lines 1875:1900 COSMC deficient cell lines 1875:1900 RESULTS Tn antigen expression was induced on various O-GalNAc glycoproteins in COSMC deficient cell lines compared to the control. 26021314 15 145 theme Tn/STn 2556:2561 arg1 expression 2564:2573 altered O-glycan (Tn/STn) expression 2538:2573 altered O-glycan (Tn/STn) expression 2538:2573 CONCLUSION This study substantiates the influence of altered O-glycan (Tn/STn) expression on oncogenic properties in pancreatic cancer and identifies O-GalNAc modified Nucleolin as novel prognostic marker. 26021314 9 146 theme based 1529:1533 arg1 enrichment 1548:1557 Lectin based glycoprotein enrichment 1522:1557 Lectin based glycoprotein enrichment with subsequent mass spectrometric analysis 1522:1601 Lectin based glycoprotein enrichment with subsequent mass spectrometric analysis identified new cancer O-GalNAc modified proteins. 26021314 14 147 dep derived 2366:2372 arg1 patient 2358:2364 patient 2358:2364 patient 2358:2364 Interestingly, immunohistochemical staining and co-localization studies of patient derived PDACs revealed poor survival for patients with strong co-localization of Tn antigen and Nucleolin (p = 0.037). 26021314 4 148 located detected 610:617 arg1 % 628:628 75-90 % 622:628 75-90 % of PDACs 622:637 Tn antigen is a tumor associated glycan detected in 75-90 % of PDACs and up to 67 % in its precursor lesions. 26021314 4 148 located detected 610:617 arg2 glycan 603:608 a tumor associated glycan 584:608 a tumor associated glycan detected in 75-90 % of PDACs and up to 67 % in its precursor lesions 584:677 Tn antigen is a tumor associated glycan detected in 75-90 % of PDACs and up to 67 % in its precursor lesions. 26021314 4 148 located detected 610:617 arg2 antigen 573:579 Tn antigen 570:579 Tn antigen 570:579 Tn antigen is a tumor associated glycan detected in 75-90 % of PDACs and up to 67 % in its precursor lesions. 26021314 4 148 located detected 610:617 arg1 % 652:652 up to 67 % 643:652 up to 67 % in its precursor lesions 643:677 Tn antigen is a tumor associated glycan detected in 75-90 % of PDACs and up to 67 % in its precursor lesions. 26021314 4 148 located detected 610:617 arg1 PDACs 633:637 PDACs 633:637 PDACs 633:637 Tn antigen is a tumor associated glycan detected in 75-90 % of PDACs and up to 67 % in its precursor lesions. 26021314 5 149 theme expression 809:818 arg1 impact 773:778 the impact 769:778 the impact of COSMC mediated Tn antigen expression in two human PDAC cell lines on cellular oncogenic properties 769:880 Since the role of Tn antigen expression in PDAC is insufficiently understood we analyzed the impact of COSMC mediated Tn antigen expression in two human PDAC cell lines on cellular oncogenic properties. 26021314 15 150 theme O-glycan 2546:2553 arg1 expression 2564:2573 altered O-glycan (Tn/STn) expression 2538:2573 altered O-glycan (Tn/STn) expression 2538:2573 CONCLUSION This study substantiates the influence of altered O-glycan (Tn/STn) expression on oncogenic properties in pancreatic cancer and identifies O-GalNAc modified Nucleolin as novel prognostic marker. 26021314 10 151 theme Tn 1667:1668 arg1 antigen 1670:1676 Tn antigen 1667:1676 Tn antigen bearing Nucleolin in patient derived PDAC tumor specimens 1667:1734 Expression of Tn antigen bearing Nucleolin in patient derived PDAC tumor specimens was evaluated and correlated with clinicopathological data. 26021314 15 152 theme prognostic 2672:2681 arg1 marker 2683:2688 novel prognostic marker 2666:2688 novel prognostic marker 2666:2688 CONCLUSION This study substantiates the influence of altered O-glycan (Tn/STn) expression on oncogenic properties in pancreatic cancer and identifies O-GalNAc modified Nucleolin as novel prognostic marker. 26021314 14 153 link derived 2366:2372 arg1 PDACs 2374:2378 patient derived PDACs 2358:2378 patient derived PDACs 2358:2378 Interestingly, immunohistochemical staining and co-localization studies of patient derived PDACs revealed poor survival for patients with strong co-localization of Tn antigen and Nucleolin (p = 0.037). 26021314 6 154 theme initial 1093:1099 arg1 residue 1111:1117 the initial GalNAcα1- residue 1089:1117 the initial GalNAcα1- residue on O-linked glycoproteins 1089:1143 METHODS Forced expression of Tn antigen on O-glycosylated proteins in pancreatic cancer cells was induced by lentiviral-mediated knockdown of the COSMC chaperone, which prevented O-glycan elongation beyond the initial GalNAcα1- residue on O-linked glycoproteins. 26021314 4 155 theme associated 592:601 arg1 glycan 603:608 a tumor associated glycan 584:608 a tumor associated glycan detected in 75-90 % of PDACs and up to 67 % in its precursor lesions 584:677 Tn antigen is a tumor associated glycan detected in 75-90 % of PDACs and up to 67 % in its precursor lesions. 26021314 4 155 theme associated 592:601 arg1 antigen 573:579 Tn antigen 570:579 Tn antigen 570:579 Tn antigen is a tumor associated glycan detected in 75-90 % of PDACs and up to 67 % in its precursor lesions. 26021314 2 156 theme GalNAc 388:393 arg1 glycosylation 396:408 a truncated O-linked N-acetylgalactosamine (GalNAc) glycosylation 344:408 a truncated O-linked N-acetylgalactosamine (GalNAc) glycosylation with expression of the Tn antigen 344:442 A frequently detected alteration in PDACs is a truncated O-linked N-acetylgalactosamine (GalNAc) glycosylation with expression of the Tn antigen. 26021314 2 156 theme GalNAc 388:393 arg1 alteration 321:330 A frequently detected alteration 299:330 A frequently detected alteration in PDACs 299:339 A frequently detected alteration in PDACs is a truncated O-linked N-acetylgalactosamine (GalNAc) glycosylation with expression of the Tn antigen. 26021314 0 157 theme aberrant 25:32 arg1 O-glycosylation 34:48 aberrant O-glycosylation 25:48 aberrant O-glycosylation promotes oncogenic properties in pancreatic cancer 25:99 COSMC knockdown mediated aberrant O-glycosylation promotes oncogenic properties in pancreatic cancer. 26021314 1 158 theme pancreatic 119:128 arg1 PDAC 153:156 PDAC 153:156 PDAC 153:156 BACKGROUND Human pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal malignancies in the world and despite great efforts in research types of treatment remain limited. 26021314 1 158 theme pancreatic 119:128 arg1 adenocarcinoma 137:150 Human pancreatic ductal adenocarcinoma 113:150 Human pancreatic ductal adenocarcinoma (PDAC) 113:157 BACKGROUND Human pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal malignancies in the world and despite great efforts in research types of treatment remain limited. 26021314 2 159 theme antigen 436:442 arg1 expression 415:424 expression 415:424 expression of the Tn antigen 415:442 A frequently detected alteration in PDACs is a truncated O-linked N-acetylgalactosamine (GalNAc) glycosylation with expression of the Tn antigen. 26021314 9 160 with enrichment 1548:1557 arg1 analysis 1594:1601 subsequent mass spectrometric analysis 1564:1601 subsequent mass spectrometric analysis 1564:1601 Lectin based glycoprotein enrichment with subsequent mass spectrometric analysis identified new cancer O-GalNAc modified proteins. 26021314 11 161 theme antigen 1807:1813 arg1 expression 1815:1824 Tn antigen expression 1804:1824 Tn antigen expression 1804:1824 RESULTS Tn antigen expression was induced on various O-GalNAc glycoproteins in COSMC deficient cell lines compared to the control. 26021314 14 162 theme poor 2389:2392 arg1 survival 2394:2401 poor survival 2389:2401 poor survival for patients with strong co-localization of Tn antigen and Nucleolin (p = 0.037) 2389:2482 Interestingly, immunohistochemical staining and co-localization studies of patient derived PDACs revealed poor survival for patients with strong co-localization of Tn antigen and Nucleolin (p = 0.037). 26021314 3 163 theme modified 499:506 arg1 proteins 517:524 posttranslationally modified O-GalNAc proteins 479:524 posttranslationally modified O-GalNAc proteins resulting in profound cellular alterations 479:567 Changes in O-glycosylation affect posttranslationally modified O-GalNAc proteins resulting in profound cellular alterations. 26021314 5 164 theme COSMC 783:787 arg1 expression 809:818 COSMC mediated Tn antigen expression 783:818 COSMC mediated Tn antigen expression in two human PDAC cell lines 783:847 Since the role of Tn antigen expression in PDAC is insufficiently understood we analyzed the impact of COSMC mediated Tn antigen expression in two human PDAC cell lines on cellular oncogenic properties. 26021314 6 165 theme O-glycan 1062:1069 arg1 elongation 1071:1080 O-glycan elongation 1062:1080 O-glycan elongation 1062:1080 METHODS Forced expression of Tn antigen on O-glycosylated proteins in pancreatic cancer cells was induced by lentiviral-mediated knockdown of the COSMC chaperone, which prevented O-glycan elongation beyond the initial GalNAcα1- residue on O-linked glycoproteins. 26021314 5 166 theme Tn 798:799 arg1 expression 809:818 COSMC mediated Tn antigen expression 783:818 COSMC mediated Tn antigen expression in two human PDAC cell lines 783:847 Since the role of Tn antigen expression in PDAC is insufficiently understood we analyzed the impact of COSMC mediated Tn antigen expression in two human PDAC cell lines on cellular oncogenic properties. 26021314 12 167 link derived 2178:2184 arg1 cells 2186:2190 PDAC derived cells 2173:2190 PDAC derived cells 2173:2190 Proliferation was reduced (p < 0.001) in COSMC knockdown cells, whereas migration was increased (p < 0.001) and apoptosis was decreased (p = 0.03), highlighting the importance of Tn antigen expression on metastatic and anti-apoptotic behavior of PDAC derived cells. 26021314 15 168 theme altered 2538:2544 arg1 expression 2564:2573 altered O-glycan (Tn/STn) expression 2538:2573 altered O-glycan (Tn/STn) expression 2538:2573 CONCLUSION This study substantiates the influence of altered O-glycan (Tn/STn) expression on oncogenic properties in pancreatic cancer and identifies O-GalNAc modified Nucleolin as novel prognostic marker. 26021314 6 169 from proteins 941:948 arg1 cells 971:975 pancreatic cancer cells 953:975 pancreatic cancer cells 953:975 METHODS Forced expression of Tn antigen on O-glycosylated proteins in pancreatic cancer cells was induced by lentiviral-mediated knockdown of the COSMC chaperone, which prevented O-glycan elongation beyond the initial GalNAcα1- residue on O-linked glycoproteins. 26021314 6 170 link O-linked 1122:1129 arg1 glycoproteins 1131:1143 O-linked glycoproteins 1122:1143 O-linked glycoproteins 1122:1143 METHODS Forced expression of Tn antigen on O-glycosylated proteins in pancreatic cancer cells was induced by lentiviral-mediated knockdown of the COSMC chaperone, which prevented O-glycan elongation beyond the initial GalNAcα1- residue on O-linked glycoproteins. 26021314 8 171 theme cell 1461:1464 arg1 imaging 1466:1472 live cell imaging 1456:1472 live cell imaging 1456:1472 To assess the biological implications of COSMC function on oncogenic properties, cell viability assays, scratch assays combined with live cell imaging, migration and apoptosis assays were performed. 26021314 12 172 theme COSMC 1968:1972 arg1 cells 1984:1988 COSMC knockdown cells 1968:1988 COSMC knockdown cells 1968:1988 Proliferation was reduced (p < 0.001) in COSMC knockdown cells, whereas migration was increased (p < 0.001) and apoptosis was decreased (p = 0.03), highlighting the importance of Tn antigen expression on metastatic and anti-apoptotic behavior of PDAC derived cells. 26021314 8 173 theme viability 1409:1417 arg1 assays 1499:1504 migration and apoptosis assays 1475:1504 migration and apoptosis assays 1475:1504 To assess the biological implications of COSMC function on oncogenic properties, cell viability assays, scratch assays combined with live cell imaging, migration and apoptosis assays were performed. 26021314 8 173 theme viability 1409:1417 arg1 assays 1419:1424 cell viability assays 1404:1424 cell viability assays 1404:1424 To assess the biological implications of COSMC function on oncogenic properties, cell viability assays, scratch assays combined with live cell imaging, migration and apoptosis assays were performed. 26021314 8 173 theme viability 1409:1417 arg1 assays 1435:1440 scratch assays 1427:1440 scratch assays combined with live cell imaging 1427:1472 To assess the biological implications of COSMC function on oncogenic properties, cell viability assays, scratch assays combined with live cell imaging, migration and apoptosis assays were performed. 26021314 15 174 theme O-GalNAc 2635:2642 arg1 Nucleolin 2653:2661 O-GalNAc modified Nucleolin 2635:2661 O-GalNAc modified Nucleolin 2635:2661 CONCLUSION This study substantiates the influence of altered O-glycan (Tn/STn) expression on oncogenic properties in pancreatic cancer and identifies O-GalNAc modified Nucleolin as novel prognostic marker. 26021314 7 175 theme immunocytochemical 1292:1309 arg1 techniques 1311:1320 Western and Far-Western blot as well as immunocytochemical techniques 1252:1320 Western and Far-Western blot as well as immunocytochemical techniques 1252:1320 Altered O-GalNAc glycosylation was analyzed in human pancreatic cancer cell lines Panc-1 and L3.6pl using Western and Far-Western blot as well as immunocytochemical techniques. 26021314 14 176 theme derived 2366:2372 arg1 PDACs 2374:2378 patient derived PDACs 2358:2378 patient derived PDACs 2358:2378 Interestingly, immunohistochemical staining and co-localization studies of patient derived PDACs revealed poor survival for patients with strong co-localization of Tn antigen and Nucleolin (p = 0.037). 26021314 3 177 from Changes 445:451 arg1 O-glycosylation 456:470 O-glycosylation 456:470 O-glycosylation 456:470 Changes in O-glycosylation affect posttranslationally modified O-GalNAc proteins resulting in profound cellular alterations. 26021314 2 178 theme N-acetylgalactosamine 365:385 arg1 glycosylation 396:408 a truncated O-linked N-acetylgalactosamine (GalNAc) glycosylation 344:408 a truncated O-linked N-acetylgalactosamine (GalNAc) glycosylation with expression of the Tn antigen 344:442 A frequently detected alteration in PDACs is a truncated O-linked N-acetylgalactosamine (GalNAc) glycosylation with expression of the Tn antigen. 26021314 2 178 theme N-acetylgalactosamine 365:385 arg1 alteration 321:330 A frequently detected alteration 299:330 A frequently detected alteration in PDACs 299:339 A frequently detected alteration in PDACs is a truncated O-linked N-acetylgalactosamine (GalNAc) glycosylation with expression of the Tn antigen. 26021314 5 179 from role 690:693 arg1 PDAC 723:726 PDAC 723:726 PDAC 723:726 Since the role of Tn antigen expression in PDAC is insufficiently understood we analyzed the impact of COSMC mediated Tn antigen expression in two human PDAC cell lines on cellular oncogenic properties. 28728943 8 0 theme Ost3p/Ost6p 997:1007 arg1 subunit 1009:1015 Ost3p/Ost6p subunit 997:1015 Ost3p/Ost6p subunit 997:1015 It bridges catalytic subunit Stt3p to Ost3p/Ost6p subunit. 28728943 3 1 theme asparagine 530:539 arg1 residue 541:547 a consensus asparagine residue 518:547 a consensus asparagine residue in the newly synthesized protein 518:580 In the central reaction, a carbohydrate group is transferred to the side chain of a consensus asparagine residue in the newly synthesized protein. 28728943 10 2 theme Ost4p 1225:1229 arg1 characterization 1205:1220 characterization 1205:1220 characterization of Ost4p 1205:1229 To understand the structure, function and role of Ost4p in N-glycosylation, characterization of Ost4p and its functionally important mutant/s are critical. 28728943 10 2 theme Ost4p 1225:1229 arg1 mutant/s 1262:1269 its functionally important mutant/s 1235:1269 its functionally important mutant/s 1235:1269 To understand the structure, function and role of Ost4p in N-glycosylation, characterization of Ost4p and its functionally important mutant/s are critical. 28728943 12 3 theme CD 1502:1503 arg1 data 1513:1516 CD and NMR data 1502:1516 CD and NMR data 1502:1516 CD and NMR data suggest that mutation of Val23 to Asp impacts the secondary structure and conformation of Ost4p. 28728943 3 4 theme residue 541:547 arg1 chain 509:513 the side chain 500:513 the side chain of a consensus asparagine residue in the newly synthesized protein 500:580 In the central reaction, a carbohydrate group is transferred to the side chain of a consensus asparagine residue in the newly synthesized protein. 28728943 3 5 from protein 574:580 arg1 chain 509:513 the side chain 500:513 the side chain of a consensus asparagine residue in the newly synthesized protein 500:580 In the central reaction, a carbohydrate group is transferred to the side chain of a consensus asparagine residue in the newly synthesized protein. 28728943 0 6 theme important 97:105 arg1 mutant 107:112 A functionally important mutant 82:112 Production and biophysical characterization of a mini-membrane protein, Ost4V23D: A functionally important mutant of yeast oligosaccharyltransferase subunit Ost4p. 0:162 Production and biophysical characterization of a mini-membrane protein, Ost4V23D: A functionally important mutant of yeast oligosaccharyltransferase subunit Ost4p. 28728943 5 7 from organisms 812:820 arg1 lethal 798:803 lethal 798:803 lethal 798:803 Complete loss of N-glycosylation is lethal in all organisms. 28728943 10 8 from structure 1147:1155 arg1 N-glycosylation 1188:1202 N-glycosylation 1188:1202 N-glycosylation 1188:1202 To understand the structure, function and role of Ost4p in N-glycosylation, characterization of Ost4p and its functionally important mutant/s are critical. 28728943 3 9 from residue 541:547 arg1 protein 574:580 the newly synthesized protein 552:580 the newly synthesized protein 552:580 In the central reaction, a carbohydrate group is transferred to the side chain of a consensus asparagine residue in the newly synthesized protein. 28728943 10 10 theme Ost4p 1179:1183 arg1 function 1158:1165 function 1158:1165 function 1158:1165 To understand the structure, function and role of Ost4p in N-glycosylation, characterization of Ost4p and its functionally important mutant/s are critical. 28728943 10 10 theme Ost4p 1179:1183 arg1 structure 1147:1155 structure 1147:1155 structure 1147:1155 To understand the structure, function and role of Ost4p in N-glycosylation, characterization of Ost4p and its functionally important mutant/s are critical. 28728943 10 10 theme Ost4p 1179:1183 arg1 role 1171:1174 role 1171:1174 role 1171:1174 To understand the structure, function and role of Ost4p in N-glycosylation, characterization of Ost4p and its functionally important mutant/s are critical. 28728943 5 11 theme Complete 762:769 arg1 loss 771:774 Complete loss 762:774 Complete loss of N-glycosylation 762:793 Complete loss of N-glycosylation is lethal in all organisms. 28728943 11 12 from purification 1341:1352 arg1 micelles 1377:1384 DPC micelles 1373:1384 DPC micelles 1373:1384 We report the mutagenesis, heterologous overexpression, purification, reconstitution in DPC micelles and biophysical characterization of Ost4V23D and compare its secondary structure and conformation to that of Ost4p. 28728943 8 13 theme catalytic 970:978 arg1 Stt3p 988:992 catalytic subunit Stt3p 970:992 catalytic subunit Stt3p 970:992 It bridges catalytic subunit Stt3p to Ost3p/Ost6p subunit. 28728943 4 14 theme developmental 723:735 arg1 retardation 710:720 mental retardation 703:720 mental retardation 703:720 Genetic defects in humans cause a series of disorders known as congenital disorders of glycosylation (CDG) that include mental retardation, developmental delay, hypoglycemia etc. 28728943 4 14 theme developmental 723:735 arg1 delay 737:741 developmental delay 723:741 developmental delay 723:741 Genetic defects in humans cause a series of disorders known as congenital disorders of glycosylation (CDG) that include mental retardation, developmental delay, hypoglycemia etc. 28728943 11 15 from characterization 1402:1417 arg1 micelles 1377:1384 DPC micelles 1373:1384 DPC micelles 1373:1384 We report the mutagenesis, heterologous overexpression, purification, reconstitution in DPC micelles and biophysical characterization of Ost4V23D and compare its secondary structure and conformation to that of Ost4p. 28728943 10 16 from function 1158:1165 arg1 N-glycosylation 1188:1202 N-glycosylation 1188:1202 N-glycosylation 1188:1202 To understand the structure, function and role of Ost4p in N-glycosylation, characterization of Ost4p and its functionally important mutant/s are critical. 28728943 1 17 theme proteins 190:197 arg1 glycosylation 173:185 N-linked glycosylation 164:185 N-linked glycosylation of proteins 164:197 N-linked glycosylation of proteins is an essential and highly conserved co- and post-translational protein modification reaction that occurs in all eukaryotes. 28728943 1 17 theme proteins 190:197 arg1 reaction 284:291 an essential and highly conserved co- and post-translational protein modification reaction 202:291 an essential and highly conserved co- and post-translational protein modification reaction that occurs in all eukaryotes 202:321 N-linked glycosylation of proteins is an essential and highly conserved co- and post-translational protein modification reaction that occurs in all eukaryotes. 28728943 0 18 theme mini-membrane 49:61 arg1 Ost4V23D 72:79 Ost4V23D 72:79 Ost4V23D 72:79 Production and biophysical characterization of a mini-membrane protein, Ost4V23D: A functionally important mutant of yeast oligosaccharyltransferase subunit Ost4p. 28728943 0 18 theme mini-membrane 49:61 arg1 protein 63:69 a mini-membrane protein 47:69 a mini-membrane protein 47:69 Production and biophysical characterization of a mini-membrane protein, Ost4V23D: A functionally important mutant of yeast oligosaccharyltransferase subunit Ost4p. 28728943 10 19 dep structure 1147:1155 arg1 the 1143:1145 the 1143:1145 the 1143:1145 To understand the structure, function and role of Ost4p in N-glycosylation, characterization of Ost4p and its functionally important mutant/s are critical. 28728943 7 20 contain containing 935:944 arg1 subunit 927:933 the smallest subunit 914:933 the smallest subunit containing 36 residues 914:956 Ost4p is the smallest subunit containing 36 residues. 28728943 7 20 contain containing 935:944 arg1 Ost4p 905:909 Ost4p 905:909 Ost4p 905:909 Ost4p is the smallest subunit containing 36 residues. 28728943 7 20 contain containing 935:944 arg2 residues 949:956 36 residues 946:956 36 residues 946:956 Ost4p is the smallest subunit containing 36 residues. 28728943 3 21 from chain 509:513 arg1 protein 574:580 the newly synthesized protein 552:580 the newly synthesized protein 552:580 In the central reaction, a carbohydrate group is transferred to the side chain of a consensus asparagine residue in the newly synthesized protein. 28728943 3 22 theme synthesized 562:572 arg1 protein 574:580 the newly synthesized protein 552:580 the newly synthesized protein 552:580 In the central reaction, a carbohydrate group is transferred to the side chain of a consensus asparagine residue in the newly synthesized protein. 28728943 9 23 theme Valine 1030:1035 arg1 Mutation 1018:1025 Mutation 1018:1025 Mutation of Valine (V) at position 23 in Ost4p to Aspartate (D) 1018:1080 Mutation of Valine (V) at position 23 in Ost4p to Aspartate (D) causes defects in the N-glycosylation process. 28728943 9 24 from Mutation 1018:1025 arg1 position 1044:1051 position 23 1044:1054 position 23 1044:1054 Mutation of Valine (V) at position 23 in Ost4p to Aspartate (D) causes defects in the N-glycosylation process. 28728943 9 24 from Mutation 1018:1025 arg1 Ost4p 1059:1063 Ost4p 1059:1063 Ost4p 1059:1063 Mutation of Valine (V) at position 23 in Ost4p to Aspartate (D) causes defects in the N-glycosylation process. 28728943 10 25 from role 1171:1174 arg1 N-glycosylation 1188:1202 N-glycosylation 1188:1202 N-glycosylation 1188:1202 To understand the structure, function and role of Ost4p in N-glycosylation, characterization of Ost4p and its functionally important mutant/s are critical. 28728943 11 26 theme Ost4V23D 1422:1429 arg1 reconstitution 1355:1368 reconstitution 1355:1368 reconstitution in DPC micelles 1355:1384 We report the mutagenesis, heterologous overexpression, purification, reconstitution in DPC micelles and biophysical characterization of Ost4V23D and compare its secondary structure and conformation to that of Ost4p. 28728943 11 26 theme Ost4V23D 1422:1429 arg1 purification 1341:1352 purification 1341:1352 purification 1341:1352 We report the mutagenesis, heterologous overexpression, purification, reconstitution in DPC micelles and biophysical characterization of Ost4V23D and compare its secondary structure and conformation to that of Ost4p. 28728943 11 26 theme Ost4V23D 1422:1429 arg1 mutagenesis 1299:1309 the mutagenesis 1295:1309 the mutagenesis 1295:1309 We report the mutagenesis, heterologous overexpression, purification, reconstitution in DPC micelles and biophysical characterization of Ost4V23D and compare its secondary structure and conformation to that of Ost4p. 28728943 11 26 theme Ost4V23D 1422:1429 arg1 overexpression 1325:1338 heterologous overexpression 1312:1338 heterologous overexpression 1312:1338 We report the mutagenesis, heterologous overexpression, purification, reconstitution in DPC micelles and biophysical characterization of Ost4V23D and compare its secondary structure and conformation to that of Ost4p. 28728943 11 26 theme Ost4V23D 1422:1429 arg1 characterization 1402:1417 biophysical characterization 1390:1417 biophysical characterization of Ost4V23D 1390:1429 We report the mutagenesis, heterologous overexpression, purification, reconstitution in DPC micelles and biophysical characterization of Ost4V23D and compare its secondary structure and conformation to that of Ost4p. 28728943 3 27 theme central 443:449 arg1 reaction 451:458 the central reaction 439:458 the central reaction 439:458 In the central reaction, a carbohydrate group is transferred to the side chain of a consensus asparagine residue in the newly synthesized protein. 28728943 12 28 theme NMR 1509:1511 arg1 data 1513:1516 CD and NMR data 1502:1516 CD and NMR data 1502:1516 CD and NMR data suggest that mutation of Val23 to Asp impacts the secondary structure and conformation of Ost4p. 28728943 11 29 theme heterologous 1312:1323 arg1 mutagenesis 1299:1309 the mutagenesis 1295:1309 the mutagenesis 1295:1309 We report the mutagenesis, heterologous overexpression, purification, reconstitution in DPC micelles and biophysical characterization of Ost4V23D and compare its secondary structure and conformation to that of Ost4p. 28728943 11 29 theme heterologous 1312:1323 arg1 overexpression 1325:1338 heterologous overexpression 1312:1338 heterologous overexpression 1312:1338 We report the mutagenesis, heterologous overexpression, purification, reconstitution in DPC micelles and biophysical characterization of Ost4V23D and compare its secondary structure and conformation to that of Ost4p. 28728943 6 30 theme non-identical 873:885 arg1 subunits 895:902 nine non-identical protein subunits 868:902 nine non-identical protein subunits 868:902 In Saccharomyces cerevisiae, OST consists of nine non-identical protein subunits. 28728943 1 31 theme essential 205:213 arg1 glycosylation 173:185 N-linked glycosylation 164:185 N-linked glycosylation of proteins 164:197 N-linked glycosylation of proteins is an essential and highly conserved co- and post-translational protein modification reaction that occurs in all eukaryotes. 28728943 1 31 theme essential 205:213 arg1 reaction 284:291 an essential and highly conserved co- and post-translational protein modification reaction 202:291 an essential and highly conserved co- and post-translational protein modification reaction that occurs in all eukaryotes 202:321 N-linked glycosylation of proteins is an essential and highly conserved co- and post-translational protein modification reaction that occurs in all eukaryotes. 28728943 4 32 from defects 591:597 arg1 humans 602:607 humans 602:607 humans 602:607 Genetic defects in humans cause a series of disorders known as congenital disorders of glycosylation (CDG) that include mental retardation, developmental delay, hypoglycemia etc. 28728943 4 33 theme Genetic 583:589 arg1 defects 591:597 Genetic defects 583:597 Genetic defects in humans 583:607 Genetic defects in humans cause a series of disorders known as congenital disorders of glycosylation (CDG) that include mental retardation, developmental delay, hypoglycemia etc. 28728943 0 34 theme oligosaccharyltransferase 123:147 arg1 Ost4p 157:161 yeast oligosaccharyltransferase subunit Ost4p 117:161 yeast oligosaccharyltransferase subunit Ost4p 117:161 Production and biophysical characterization of a mini-membrane protein, Ost4V23D: A functionally important mutant of yeast oligosaccharyltransferase subunit Ost4p. 28728943 9 35 from position 1044:1051 arg1 V 1038:1038 V 1038:1038 V 1038:1038 Mutation of Valine (V) at position 23 in Ost4p to Aspartate (D) causes defects in the N-glycosylation process. 28728943 9 35 from position 1044:1051 arg1 Valine 1030:1035 Valine 1030:1035 Valine (V) at position 23 1030:1054 Mutation of Valine (V) at position 23 in Ost4p to Aspartate (D) causes defects in the N-glycosylation process. 28728943 9 35 from position 1044:1051 arg1 Mutation 1018:1025 Mutation 1018:1025 Mutation of Valine (V) at position 23 in Ost4p to Aspartate (D) 1018:1080 Mutation of Valine (V) at position 23 in Ost4p to Aspartate (D) causes defects in the N-glycosylation process. 28728943 9 36 theme N-glycosylation 1104:1118 arg1 process 1120:1126 the N-glycosylation process 1100:1126 the N-glycosylation process 1100:1126 Mutation of Valine (V) at position 23 in Ost4p to Aspartate (D) causes defects in the N-glycosylation process. 28728943 0 37 theme biophysical 15:25 arg1 characterization 27:42 biophysical characterization 15:42 biophysical characterization 15:42 Production and biophysical characterization of a mini-membrane protein, Ost4V23D: A functionally important mutant of yeast oligosaccharyltransferase subunit Ost4p. 28728943 11 38 from overexpression 1325:1338 arg1 micelles 1377:1384 DPC micelles 1373:1384 DPC micelles 1373:1384 We report the mutagenesis, heterologous overexpression, purification, reconstitution in DPC micelles and biophysical characterization of Ost4V23D and compare its secondary structure and conformation to that of Ost4p. 28728943 0 39 theme yeast 117:121 arg1 Ost4p 157:161 yeast oligosaccharyltransferase subunit Ost4p 117:161 yeast oligosaccharyltransferase subunit Ost4p 117:161 Production and biophysical characterization of a mini-membrane protein, Ost4V23D: A functionally important mutant of yeast oligosaccharyltransferase subunit Ost4p. 28728943 3 40 theme side 504:507 arg1 chain 509:513 the side chain 500:513 the side chain of a consensus asparagine residue in the newly synthesized protein 500:580 In the central reaction, a carbohydrate group is transferred to the side chain of a consensus asparagine residue in the newly synthesized protein. 28728943 3 41 theme consensus 520:528 arg1 residue 541:547 a consensus asparagine residue 518:547 a consensus asparagine residue in the newly synthesized protein 518:580 In the central reaction, a carbohydrate group is transferred to the side chain of a consensus asparagine residue in the newly synthesized protein. 28728943 0 42 theme Ost4p 157:161 arg1 mutant 107:112 A functionally important mutant 82:112 Production and biophysical characterization of a mini-membrane protein, Ost4V23D: A functionally important mutant of yeast oligosaccharyltransferase subunit Ost4p. 0:162 Production and biophysical characterization of a mini-membrane protein, Ost4V23D: A functionally important mutant of yeast oligosaccharyltransferase subunit Ost4p. 28728943 3 43 theme carbohydrate 463:474 arg1 group 476:480 a carbohydrate group 461:480 a carbohydrate group 461:480 In the central reaction, a carbohydrate group is transferred to the side chain of a consensus asparagine residue in the newly synthesized protein. 28728943 1 44 theme conserved 226:234 arg1 glycosylation 173:185 N-linked glycosylation 164:185 N-linked glycosylation of proteins 164:197 N-linked glycosylation of proteins is an essential and highly conserved co- and post-translational protein modification reaction that occurs in all eukaryotes. 28728943 1 44 theme conserved 226:234 arg1 reaction 284:291 an essential and highly conserved co- and post-translational protein modification reaction 202:291 an essential and highly conserved co- and post-translational protein modification reaction that occurs in all eukaryotes 202:321 N-linked glycosylation of proteins is an essential and highly conserved co- and post-translational protein modification reaction that occurs in all eukaryotes. 28728943 11 45 theme biophysical 1390:1400 arg1 characterization 1402:1417 biophysical characterization 1390:1417 biophysical characterization of Ost4V23D 1390:1429 We report the mutagenesis, heterologous overexpression, purification, reconstitution in DPC micelles and biophysical characterization of Ost4V23D and compare its secondary structure and conformation to that of Ost4p. 28728943 11 45 theme biophysical 1390:1400 arg1 mutagenesis 1299:1309 the mutagenesis 1295:1309 the mutagenesis 1295:1309 We report the mutagenesis, heterologous overexpression, purification, reconstitution in DPC micelles and biophysical characterization of Ost4V23D and compare its secondary structure and conformation to that of Ost4p. 28728943 12 46 theme Ost4p 1608:1612 arg1 structure 1578:1586 secondary structure 1568:1586 secondary structure 1568:1586 CD and NMR data suggest that mutation of Val23 to Asp impacts the secondary structure and conformation of Ost4p. 28728943 12 46 theme Ost4p 1608:1612 arg1 conformation 1592:1603 conformation 1592:1603 conformation 1592:1603 CD and NMR data suggest that mutation of Val23 to Asp impacts the secondary structure and conformation of Ost4p. 28728943 1 47 link N-linked 164:171 arg1 glycosylation 173:185 N-linked glycosylation 164:185 N-linked glycosylation of proteins 164:197 N-linked glycosylation of proteins is an essential and highly conserved co- and post-translational protein modification reaction that occurs in all eukaryotes. 28728943 1 47 link N-linked 164:171 arg1 reaction 284:291 an essential and highly conserved co- and post-translational protein modification reaction 202:291 an essential and highly conserved co- and post-translational protein modification reaction that occurs in all eukaryotes 202:321 N-linked glycosylation of proteins is an essential and highly conserved co- and post-translational protein modification reaction that occurs in all eukaryotes. 28728943 12 48 theme Val23 1543:1547 arg1 mutation 1531:1538 mutation 1531:1538 mutation of Val23 to Asp 1531:1554 CD and NMR data suggest that mutation of Val23 to Asp impacts the secondary structure and conformation of Ost4p. 28728943 4 49 theme congenital 646:655 arg1 disorders 657:665 congenital disorders 646:665 congenital disorders of glycosylation (CDG) that include mental retardation, developmental delay, hypoglycemia etc 646:759 Genetic defects in humans cause a series of disorders known as congenital disorders of glycosylation (CDG) that include mental retardation, developmental delay, hypoglycemia etc. 28728943 4 50 theme glycosylation 670:682 arg1 disorders 657:665 congenital disorders 646:665 congenital disorders of glycosylation (CDG) that include mental retardation, developmental delay, hypoglycemia etc 646:759 Genetic defects in humans cause a series of disorders known as congenital disorders of glycosylation (CDG) that include mental retardation, developmental delay, hypoglycemia etc. 28728943 0 51 theme protein 63:69 arg1 Production 0:9 Production 0:9 Production 0:9 Production and biophysical characterization of a mini-membrane protein, Ost4V23D: A functionally important mutant of yeast oligosaccharyltransferase subunit Ost4p. 28728943 0 51 theme protein 63:69 arg1 characterization 27:42 biophysical characterization 15:42 biophysical characterization 15:42 Production and biophysical characterization of a mini-membrane protein, Ost4V23D: A functionally important mutant of yeast oligosaccharyltransferase subunit Ost4p. 28728943 11 52 theme secondary 1447:1455 arg1 structure 1457:1465 its secondary structure 1443:1465 its secondary structure 1443:1465 We report the mutagenesis, heterologous overexpression, purification, reconstitution in DPC micelles and biophysical characterization of Ost4V23D and compare its secondary structure and conformation to that of Ost4p. 28728943 6 53 theme protein 887:893 arg1 subunits 895:902 nine non-identical protein subunits 868:902 nine non-identical protein subunits 868:902 In Saccharomyces cerevisiae, OST consists of nine non-identical protein subunits. 28728943 11 54 from reconstitution 1355:1368 arg1 micelles 1377:1384 DPC micelles 1373:1384 DPC micelles 1373:1384 We report the mutagenesis, heterologous overexpression, purification, reconstitution in DPC micelles and biophysical characterization of Ost4V23D and compare its secondary structure and conformation to that of Ost4p. 28728943 2 55 theme enzyme 393:398 arg1 Oligosaccharyltransferase 324:348 Oligosaccharyltransferase 324:348 Oligosaccharyltransferase (OST) 324:354 Oligosaccharyltransferase (OST), a multi-subunit membrane-associated enzyme complex, carries out this reaction. 28728943 2 55 theme enzyme 393:398 arg1 complex 400:406 a multi-subunit membrane-associated enzyme complex 357:406 a multi-subunit membrane-associated enzyme complex 357:406 Oligosaccharyltransferase (OST), a multi-subunit membrane-associated enzyme complex, carries out this reaction. 28728943 0 56 theme subunit 149:155 arg1 Ost4p 157:161 yeast oligosaccharyltransferase subunit Ost4p 117:161 yeast oligosaccharyltransferase subunit Ost4p 117:161 Production and biophysical characterization of a mini-membrane protein, Ost4V23D: A functionally important mutant of yeast oligosaccharyltransferase subunit Ost4p. 28728943 5 57 from lethal 798:803 arg1 organisms 812:820 all organisms 808:820 all organisms 808:820 Complete loss of N-glycosylation is lethal in all organisms. 28728943 8 58 theme subunit 980:986 arg1 Stt3p 988:992 catalytic subunit Stt3p 970:992 catalytic subunit Stt3p 970:992 It bridges catalytic subunit Stt3p to Ost3p/Ost6p subunit. 28728943 2 59 theme membrane-associated 373:391 arg1 Oligosaccharyltransferase 324:348 Oligosaccharyltransferase 324:348 Oligosaccharyltransferase (OST) 324:354 Oligosaccharyltransferase (OST), a multi-subunit membrane-associated enzyme complex, carries out this reaction. 28728943 2 59 theme membrane-associated 373:391 arg1 complex 400:406 a multi-subunit membrane-associated enzyme complex 357:406 a multi-subunit membrane-associated enzyme complex 357:406 Oligosaccharyltransferase (OST), a multi-subunit membrane-associated enzyme complex, carries out this reaction. 28728943 10 60 theme important 1252:1260 arg1 mutant/s 1262:1269 its functionally important mutant/s 1235:1269 its functionally important mutant/s 1235:1269 To understand the structure, function and role of Ost4p in N-glycosylation, characterization of Ost4p and its functionally important mutant/s are critical. 28728943 9 61 from defects 1089:1095 arg1 process 1120:1126 the N-glycosylation process 1100:1126 the N-glycosylation process 1100:1126 Mutation of Valine (V) at position 23 in Ost4p to Aspartate (D) causes defects in the N-glycosylation process. 28728943 1 62 dep conserved 226:234 arg1 post-translational 244:261 post-translational 244:261 post-translational 244:261 N-linked glycosylation of proteins is an essential and highly conserved co- and post-translational protein modification reaction that occurs in all eukaryotes. 28728943 1 62 dep conserved 226:234 arg1 co- 236:238 co- 236:238 co- 236:238 N-linked glycosylation of proteins is an essential and highly conserved co- and post-translational protein modification reaction that occurs in all eukaryotes. 28728943 4 63 theme mental 703:708 arg1 retardation 710:720 mental retardation 703:720 mental retardation 703:720 Genetic defects in humans cause a series of disorders known as congenital disorders of glycosylation (CDG) that include mental retardation, developmental delay, hypoglycemia etc. 28728943 4 63 theme mental 703:708 arg1 delay 737:741 developmental delay 723:741 developmental delay 723:741 Genetic defects in humans cause a series of disorders known as congenital disorders of glycosylation (CDG) that include mental retardation, developmental delay, hypoglycemia etc. 28728943 4 63 theme mental 703:708 arg1 etc 757:759 hypoglycemia etc 744:759 hypoglycemia etc 744:759 Genetic defects in humans cause a series of disorders known as congenital disorders of glycosylation (CDG) that include mental retardation, developmental delay, hypoglycemia etc. 28728943 2 64 theme multi-subunit 359:371 arg1 Oligosaccharyltransferase 324:348 Oligosaccharyltransferase 324:348 Oligosaccharyltransferase (OST) 324:354 Oligosaccharyltransferase (OST), a multi-subunit membrane-associated enzyme complex, carries out this reaction. 28728943 2 64 theme multi-subunit 359:371 arg1 complex 400:406 a multi-subunit membrane-associated enzyme complex 357:406 a multi-subunit membrane-associated enzyme complex 357:406 Oligosaccharyltransferase (OST), a multi-subunit membrane-associated enzyme complex, carries out this reaction. 28728943 1 65 gly glycosylation 173:185 arg1 proteins 190:197 proteins 190:197 proteins 190:197 N-linked glycosylation of proteins is an essential and highly conserved co- and post-translational protein modification reaction that occurs in all eukaryotes. 28728943 12 66 dep structure 1578:1586 arg1 the 1564:1566 the 1564:1566 the 1564:1566 CD and NMR data suggest that mutation of Val23 to Asp impacts the secondary structure and conformation of Ost4p. 28728943 4 67 theme hypoglycemia 744:755 arg1 retardation 710:720 mental retardation 703:720 mental retardation 703:720 Genetic defects in humans cause a series of disorders known as congenital disorders of glycosylation (CDG) that include mental retardation, developmental delay, hypoglycemia etc. 28728943 4 67 theme hypoglycemia 744:755 arg1 etc 757:759 hypoglycemia etc 744:759 hypoglycemia etc 744:759 Genetic defects in humans cause a series of disorders known as congenital disorders of glycosylation (CDG) that include mental retardation, developmental delay, hypoglycemia etc. 28728943 4 68 theme disorders 627:635 arg1 series 617:622 a series 615:622 a series of disorders known as congenital disorders of glycosylation (CDG) that include mental retardation, developmental delay, hypoglycemia etc 615:759 Genetic defects in humans cause a series of disorders known as congenital disorders of glycosylation (CDG) that include mental retardation, developmental delay, hypoglycemia etc. 28728943 5 69 theme N-glycosylation 779:793 arg1 loss 771:774 Complete loss 762:774 Complete loss of N-glycosylation 762:793 Complete loss of N-glycosylation is lethal in all organisms. 28728943 12 70 theme secondary 1568:1576 arg1 structure 1578:1586 secondary structure 1568:1586 secondary structure 1568:1586 CD and NMR data suggest that mutation of Val23 to Asp impacts the secondary structure and conformation of Ost4p. 28728943 1 71 theme protein 263:269 arg1 glycosylation 173:185 N-linked glycosylation 164:185 N-linked glycosylation of proteins 164:197 N-linked glycosylation of proteins is an essential and highly conserved co- and post-translational protein modification reaction that occurs in all eukaryotes. 28728943 1 71 theme protein 263:269 arg1 reaction 284:291 an essential and highly conserved co- and post-translational protein modification reaction 202:291 an essential and highly conserved co- and post-translational protein modification reaction that occurs in all eukaryotes 202:321 N-linked glycosylation of proteins is an essential and highly conserved co- and post-translational protein modification reaction that occurs in all eukaryotes. 28728943 11 72 theme DPC 1373:1375 arg1 micelles 1377:1384 DPC micelles 1373:1384 DPC micelles 1373:1384 We report the mutagenesis, heterologous overexpression, purification, reconstitution in DPC micelles and biophysical characterization of Ost4V23D and compare its secondary structure and conformation to that of Ost4p. 28728943 0 73 dep Production 0:9 arg1 mutant 107:112 A functionally important mutant 82:112 Production and biophysical characterization of a mini-membrane protein, Ost4V23D: A functionally important mutant of yeast oligosaccharyltransferase subunit Ost4p. 0:162 Production and biophysical characterization of a mini-membrane protein, Ost4V23D: A functionally important mutant of yeast oligosaccharyltransferase subunit Ost4p. 28728943 1 74 theme N-linked 164:171 arg1 glycosylation 173:185 N-linked glycosylation 164:185 N-linked glycosylation of proteins 164:197 N-linked glycosylation of proteins is an essential and highly conserved co- and post-translational protein modification reaction that occurs in all eukaryotes. 28728943 1 74 theme N-linked 164:171 arg1 reaction 284:291 an essential and highly conserved co- and post-translational protein modification reaction 202:291 an essential and highly conserved co- and post-translational protein modification reaction that occurs in all eukaryotes 202:321 N-linked glycosylation of proteins is an essential and highly conserved co- and post-translational protein modification reaction that occurs in all eukaryotes. 28728943 7 75 theme smallest 918:925 arg1 subunit 927:933 the smallest subunit 914:933 the smallest subunit containing 36 residues 914:956 Ost4p is the smallest subunit containing 36 residues. 28728943 7 75 theme smallest 918:925 arg1 Ost4p 905:909 Ost4p 905:909 Ost4p 905:909 Ost4p is the smallest subunit containing 36 residues. 28728943 1 76 theme modification 271:282 arg1 glycosylation 173:185 N-linked glycosylation 164:185 N-linked glycosylation of proteins 164:197 N-linked glycosylation of proteins is an essential and highly conserved co- and post-translational protein modification reaction that occurs in all eukaryotes. 28728943 1 76 theme modification 271:282 arg1 reaction 284:291 an essential and highly conserved co- and post-translational protein modification reaction 202:291 an essential and highly conserved co- and post-translational protein modification reaction that occurs in all eukaryotes 202:321 N-linked glycosylation of proteins is an essential and highly conserved co- and post-translational protein modification reaction that occurs in all eukaryotes. 28451135 4 0 theme anti-rhamnosyl 899:912 arg1 anti-ArgRha 942:952 anti-ArgRha 942:952 anti-ArgRha 942:952 Based on this finding we describe the synthesis of an α-rhamnosylated arginine containing peptide antigen in order to raise the first anti-rhamnosyl arginine specific antibody (anti-ArgRha). 28451135 4 0 theme anti-rhamnosyl 899:912 arg1 antibody 932:939 the first anti-rhamnosyl arginine specific antibody 889:939 the first anti-rhamnosyl arginine specific antibody (anti-ArgRha) 889:953 Based on this finding we describe the synthesis of an α-rhamnosylated arginine containing peptide antigen in order to raise the first anti-rhamnosyl arginine specific antibody (anti-ArgRha). 28451135 8 1 theme drug 1486:1489 arg1 discovery 1491:1499 drug discovery 1486:1499 drug discovery 1486:1499 As EF-P rhamnosylation is essential for pathogenicity, our antibody might also be a powerful tool in drug discovery. 28451135 1 2 theme posttranslational 176:192 arg1 modification 194:205 A previously discovered posttranslational modification 152:205 A previously discovered posttranslational modification strategy - arginine rhamnosylation - 152:242 A previously discovered posttranslational modification strategy - arginine rhamnosylation - is essential for elongation factor P (EF-P) dependent rescue of polyproline stalled ribosomes in clinically relevant species such as Pseudomonas aeruginosa and Neisseria meningitidis. 28451135 5 3 gly N-glycosylated 1087:1100 arg1 proteins 1102:1109 other N-glycosylated proteins 1081:1109 other N-glycosylated proteins 1081:1109 Using ELISA and Western Blot analyses we demonstrated both its high affinity and specificity without any cross-reactivity to other N-glycosylated proteins. 28451135 1 4 from rescue 298:303 arg1 aeruginosa 389:398 Pseudomonas aeruginosa 377:398 Pseudomonas aeruginosa 377:398 A previously discovered posttranslational modification strategy - arginine rhamnosylation - is essential for elongation factor P (EF-P) dependent rescue of polyproline stalled ribosomes in clinically relevant species such as Pseudomonas aeruginosa and Neisseria meningitidis. 28451135 1 4 from rescue 298:303 arg1 meningitidis 414:425 Neisseria meningitidis 404:425 Neisseria meningitidis 404:425 A previously discovered posttranslational modification strategy - arginine rhamnosylation - is essential for elongation factor P (EF-P) dependent rescue of polyproline stalled ribosomes in clinically relevant species such as Pseudomonas aeruginosa and Neisseria meningitidis. 28451135 1 4 from rescue 298:303 arg1 species 361:367 clinically relevant species 341:367 clinically relevant species such as Pseudomonas aeruginosa and Neisseria meningitidis 341:425 A previously discovered posttranslational modification strategy - arginine rhamnosylation - is essential for elongation factor P (EF-P) dependent rescue of polyproline stalled ribosomes in clinically relevant species such as Pseudomonas aeruginosa and Neisseria meningitidis. 28451135 4 5 theme first 893:897 arg1 anti-ArgRha 942:952 anti-ArgRha 942:952 anti-ArgRha 942:952 Based on this finding we describe the synthesis of an α-rhamnosylated arginine containing peptide antigen in order to raise the first anti-rhamnosyl arginine specific antibody (anti-ArgRha). 28451135 4 5 theme first 893:897 arg1 antibody 932:939 the first anti-rhamnosyl arginine specific antibody 889:939 the first anti-rhamnosyl arginine specific antibody (anti-ArgRha) 889:953 Based on this finding we describe the synthesis of an α-rhamnosylated arginine containing peptide antigen in order to raise the first anti-rhamnosyl arginine specific antibody (anti-ArgRha). 28451135 1 6 theme modification 194:205 arg1 strategy 207:214 A previously discovered posttranslational modification strategy 152:214 A previously discovered posttranslational modification strategy - arginine rhamnosylation - 152:242 A previously discovered posttranslational modification strategy - arginine rhamnosylation - is essential for elongation factor P (EF-P) dependent rescue of polyproline stalled ribosomes in clinically relevant species such as Pseudomonas aeruginosa and Neisseria meningitidis. 28451135 8 7 theme powerful 1469:1476 arg1 tool 1478:1481 a powerful tool 1467:1481 a powerful tool in drug discovery 1467:1499 As EF-P rhamnosylation is essential for pathogenicity, our antibody might also be a powerful tool in drug discovery. 28451135 8 7 theme powerful 1469:1476 arg1 antibody 1444:1451 our antibody 1440:1451 our antibody 1440:1451 As EF-P rhamnosylation is essential for pathogenicity, our antibody might also be a powerful tool in drug discovery. 28451135 4 8 theme specific 923:930 arg1 anti-ArgRha 942:952 anti-ArgRha 942:952 anti-ArgRha 942:952 Based on this finding we describe the synthesis of an α-rhamnosylated arginine containing peptide antigen in order to raise the first anti-rhamnosyl arginine specific antibody (anti-ArgRha). 28451135 4 8 theme specific 923:930 arg1 antibody 932:939 the first anti-rhamnosyl arginine specific antibody 889:939 the first anti-rhamnosyl arginine specific antibody (anti-ArgRha) 889:953 Based on this finding we describe the synthesis of an α-rhamnosylated arginine containing peptide antigen in order to raise the first anti-rhamnosyl arginine specific antibody (anti-ArgRha). 28451135 3 9 used used 532:535 arg2 we 529:530 we 529:530 we 529:530 In the present study we used NMR spectroscopy to show for the first time that the α anomer of rhamnose is attached to Arg32 of EF-P, demonstrating that the corresponding glycosyltransferase EarP inverts the sugar of its cognate substrate dTDP-β-l-rhamnose. 28451135 3 10 theme first 570:574 arg1 time 576:579 the first time 566:579 the first time 566:579 In the present study we used NMR spectroscopy to show for the first time that the α anomer of rhamnose is attached to Arg32 of EF-P, demonstrating that the corresponding glycosyltransferase EarP inverts the sugar of its cognate substrate dTDP-β-l-rhamnose. 28451135 1 11 theme dependent 288:296 arg1 rescue 298:303 elongation factor P (EF-P) dependent rescue 261:303 elongation factor P (EF-P) dependent rescue of polyproline stalled ribosomes in clinically relevant species such as Pseudomonas aeruginosa and Neisseria meningitidis 261:425 A previously discovered posttranslational modification strategy - arginine rhamnosylation - is essential for elongation factor P (EF-P) dependent rescue of polyproline stalled ribosomes in clinically relevant species such as Pseudomonas aeruginosa and Neisseria meningitidis. 28451135 5 12 theme Western 972:978 arg1 analyses 985:992 Western Blot analyses 972:992 Western Blot analyses 972:992 Using ELISA and Western Blot analyses we demonstrated both its high affinity and specificity without any cross-reactivity to other N-glycosylated proteins. 28451135 3 13 theme dTDP-β-l-rhamnose 746:762 arg1 sugar 715:719 the sugar 711:719 the sugar of its cognate substrate dTDP-β-l-rhamnose 711:762 In the present study we used NMR spectroscopy to show for the first time that the α anomer of rhamnose is attached to Arg32 of EF-P, demonstrating that the corresponding glycosyltransferase EarP inverts the sugar of its cognate substrate dTDP-β-l-rhamnose. 28451135 4 14 theme arginine 914:921 arg1 anti-ArgRha 942:952 anti-ArgRha 942:952 anti-ArgRha 942:952 Based on this finding we describe the synthesis of an α-rhamnosylated arginine containing peptide antigen in order to raise the first anti-rhamnosyl arginine specific antibody (anti-ArgRha). 28451135 4 14 theme arginine 914:921 arg1 antibody 932:939 the first anti-rhamnosyl arginine specific antibody 889:939 the first anti-rhamnosyl arginine specific antibody (anti-ArgRha) 889:953 Based on this finding we describe the synthesis of an α-rhamnosylated arginine containing peptide antigen in order to raise the first anti-rhamnosyl arginine specific antibody (anti-ArgRha). 28451135 2 15 link N-linked 484:491 arg1 glycosylation 493:505 N-linked glycosylation 484:505 N-linked glycosylation 484:505 However, almost nothing is known about this new type of N-linked glycosylation. 28451135 3 16 theme NMR 537:539 arg1 spectroscopy 541:552 NMR spectroscopy 537:552 NMR spectroscopy 537:552 In the present study we used NMR spectroscopy to show for the first time that the α anomer of rhamnose is attached to Arg32 of EF-P, demonstrating that the corresponding glycosyltransferase EarP inverts the sugar of its cognate substrate dTDP-β-l-rhamnose. 28451135 0 17 theme ArgRha 126:131 arg1 antibody 142:149 the first ArgRha specific antibody 116:149 the first ArgRha specific antibody 116:149 Resolving the α-glycosidic linkage of arginine-rhamnosylated translation elongation factor P triggers generation of the first ArgRha specific antibody. 28451135 8 18 theme EF-P 1388:1391 arg1 rhamnosylation 1393:1406 EF-P rhamnosylation 1388:1406 EF-P rhamnosylation 1388:1406 As EF-P rhamnosylation is essential for pathogenicity, our antibody might also be a powerful tool in drug discovery. 28451135 0 19 theme first 120:124 arg1 antibody 142:149 the first ArgRha specific antibody 116:149 the first ArgRha specific antibody 116:149 Resolving the α-glycosidic linkage of arginine-rhamnosylated translation elongation factor P triggers generation of the first ArgRha specific antibody. 28451135 3 20 theme cognate 728:734 arg1 dTDP-β-l-rhamnose 746:762 its cognate substrate dTDP-β-l-rhamnose 724:762 its cognate substrate dTDP-β-l-rhamnose 724:762 In the present study we used NMR spectroscopy to show for the first time that the α anomer of rhamnose is attached to Arg32 of EF-P, demonstrating that the corresponding glycosyltransferase EarP inverts the sugar of its cognate substrate dTDP-β-l-rhamnose. 28451135 5 21 theme high 1019:1022 arg1 affinity 1024:1031 its high affinity 1015:1031 its high affinity 1015:1031 Using ELISA and Western Blot analyses we demonstrated both its high affinity and specificity without any cross-reactivity to other N-glycosylated proteins. 28451135 2 22 theme N-linked 484:491 arg1 glycosylation 493:505 N-linked glycosylation 484:505 N-linked glycosylation 484:505 However, almost nothing is known about this new type of N-linked glycosylation. 28451135 3 23 theme substrate 736:744 arg1 dTDP-β-l-rhamnose 746:762 its cognate substrate dTDP-β-l-rhamnose 724:762 its cognate substrate dTDP-β-l-rhamnose 724:762 In the present study we used NMR spectroscopy to show for the first time that the α anomer of rhamnose is attached to Arg32 of EF-P, demonstrating that the corresponding glycosyltransferase EarP inverts the sugar of its cognate substrate dTDP-β-l-rhamnose. 28451135 3 24 theme α 590:590 arg1 anomer 592:597 the α anomer 586:597 the α anomer of rhamnose 586:609 In the present study we used NMR spectroscopy to show for the first time that the α anomer of rhamnose is attached to Arg32 of EF-P, demonstrating that the corresponding glycosyltransferase EarP inverts the sugar of its cognate substrate dTDP-β-l-rhamnose. 28451135 1 25 theme arginine 218:225 arg1 rhamnosylation 227:240 arginine rhamnosylation 218:240 A previously discovered posttranslational modification strategy - arginine rhamnosylation - 152:242 A previously discovered posttranslational modification strategy - arginine rhamnosylation - is essential for elongation factor P (EF-P) dependent rescue of polyproline stalled ribosomes in clinically relevant species such as Pseudomonas aeruginosa and Neisseria meningitidis. 28451135 5 26 theme Blot 980:983 arg1 analyses 985:992 Western Blot analyses 972:992 Western Blot analyses 972:992 Using ELISA and Western Blot analyses we demonstrated both its high affinity and specificity without any cross-reactivity to other N-glycosylated proteins. 28451135 1 27 theme polyproline 308:318 arg1 ribosomes 328:336 polyproline stalled ribosomes 308:336 polyproline stalled ribosomes 308:336 A previously discovered posttranslational modification strategy - arginine rhamnosylation - is essential for elongation factor P (EF-P) dependent rescue of polyproline stalled ribosomes in clinically relevant species such as Pseudomonas aeruginosa and Neisseria meningitidis. 28451135 0 28 theme antibody 142:149 arg1 generation 102:111 generation 102:111 generation of the first ArgRha specific antibody 102:149 Resolving the α-glycosidic linkage of arginine-rhamnosylated translation elongation factor P triggers generation of the first ArgRha specific antibody. 28451135 5 29 theme other 1081:1085 arg1 proteins 1102:1109 other N-glycosylated proteins 1081:1109 other N-glycosylated proteins 1081:1109 Using ELISA and Western Blot analyses we demonstrated both its high affinity and specificity without any cross-reactivity to other N-glycosylated proteins. 28451135 5 30 theme N-glycosylated 1087:1100 arg1 proteins 1102:1109 other N-glycosylated proteins 1081:1109 other N-glycosylated proteins 1081:1109 Using ELISA and Western Blot analyses we demonstrated both its high affinity and specificity without any cross-reactivity to other N-glycosylated proteins. 28451135 7 31 theme arginine 1355:1362 arg1 proteins 1375:1382 rhamnosyl arginine containing proteins 1345:1382 rhamnosyl arginine containing proteins 1345:1382 Thus, we expect the antibody to be not only important to monitor EF-P rhamnosylation in diverse bacteria but also to identify further rhamnosyl arginine containing proteins. 28451135 0 32 theme α-glycosidic 14:25 arg1 linkage 27:33 the α-glycosidic linkage 10:33 the α-glycosidic linkage of arginine-rhamnosylated translation elongation factor P 10:91 Resolving the α-glycosidic linkage of arginine-rhamnosylated translation elongation factor P triggers generation of the first ArgRha specific antibody. 28451135 1 33 theme stalled 320:326 arg1 ribosomes 328:336 polyproline stalled ribosomes 308:336 polyproline stalled ribosomes 308:336 A previously discovered posttranslational modification strategy - arginine rhamnosylation - is essential for elongation factor P (EF-P) dependent rescue of polyproline stalled ribosomes in clinically relevant species such as Pseudomonas aeruginosa and Neisseria meningitidis. 28451135 0 34 theme specific 133:140 arg1 antibody 142:149 the first ArgRha specific antibody 116:149 the first ArgRha specific antibody 116:149 Resolving the α-glycosidic linkage of arginine-rhamnosylated translation elongation factor P triggers generation of the first ArgRha specific antibody. 28451135 6 35 dep able 1151:1154 arg1 Having 1112:1117 Having 1112:1117 Having the anti-ArgRha at hand 1112:1141 Having the anti-ArgRha at hand we were able to visualize endogenously produced rhamnosylated EF-P. 28451135 8 36 from tool 1478:1481 arg1 discovery 1491:1499 drug discovery 1486:1499 drug discovery 1486:1499 As EF-P rhamnosylation is essential for pathogenicity, our antibody might also be a powerful tool in drug discovery. 28451135 7 37 theme containing 1364:1373 arg1 proteins 1375:1382 rhamnosyl arginine containing proteins 1345:1382 rhamnosyl arginine containing proteins 1345:1382 Thus, we expect the antibody to be not only important to monitor EF-P rhamnosylation in diverse bacteria but also to identify further rhamnosyl arginine containing proteins. 28451135 0 38 theme arginine-rhamnosylated 38:59 arg1 factor 84:89 arginine-rhamnosylated translation elongation factor 38:89 arginine-rhamnosylated translation elongation factor P 38:91 Resolving the α-glycosidic linkage of arginine-rhamnosylated translation elongation factor P triggers generation of the first ArgRha specific antibody. 28451135 1 39 theme ribosomes 328:336 arg1 rescue 298:303 elongation factor P (EF-P) dependent rescue 261:303 elongation factor P (EF-P) dependent rescue of polyproline stalled ribosomes in clinically relevant species such as Pseudomonas aeruginosa and Neisseria meningitidis 261:425 A previously discovered posttranslational modification strategy - arginine rhamnosylation - is essential for elongation factor P (EF-P) dependent rescue of polyproline stalled ribosomes in clinically relevant species such as Pseudomonas aeruginosa and Neisseria meningitidis. 28451135 4 40 theme peptide 855:861 arg1 antigen 863:869 peptide antigen 855:869 peptide antigen in order to raise the first anti-rhamnosyl arginine specific antibody (anti-ArgRha) 855:953 Based on this finding we describe the synthesis of an α-rhamnosylated arginine containing peptide antigen in order to raise the first anti-rhamnosyl arginine specific antibody (anti-ArgRha). 28451135 4 41 contain containing 844:853 arg1 arginine 835:842 an α-rhamnosylated arginine 816:842 an α-rhamnosylated arginine containing peptide antigen in order to raise the first anti-rhamnosyl arginine specific antibody (anti-ArgRha) 816:953 Based on this finding we describe the synthesis of an α-rhamnosylated arginine containing peptide antigen in order to raise the first anti-rhamnosyl arginine specific antibody (anti-ArgRha). 28451135 4 41 contain containing 844:853 arg2 antigen 863:869 peptide antigen 855:869 peptide antigen in order to raise the first anti-rhamnosyl arginine specific antibody (anti-ArgRha) 855:953 Based on this finding we describe the synthesis of an α-rhamnosylated arginine containing peptide antigen in order to raise the first anti-rhamnosyl arginine specific antibody (anti-ArgRha). 28451135 7 42 theme rhamnosyl 1345:1353 arg1 proteins 1375:1382 rhamnosyl arginine containing proteins 1345:1382 rhamnosyl arginine containing proteins 1345:1382 Thus, we expect the antibody to be not only important to monitor EF-P rhamnosylation in diverse bacteria but also to identify further rhamnosyl arginine containing proteins. 28451135 0 43 theme elongation 73:82 arg1 factor 84:89 arginine-rhamnosylated translation elongation factor 38:89 arginine-rhamnosylated translation elongation factor P 38:91 Resolving the α-glycosidic linkage of arginine-rhamnosylated translation elongation factor P triggers generation of the first ArgRha specific antibody. 28451135 7 44 theme EF-P 1276:1279 arg1 rhamnosylation 1281:1294 EF-P rhamnosylation 1276:1294 EF-P rhamnosylation 1276:1294 Thus, we expect the antibody to be not only important to monitor EF-P rhamnosylation in diverse bacteria but also to identify further rhamnosyl arginine containing proteins. 28451135 1 45 dep strategy 207:214 arg1 rhamnosylation 227:240 arginine rhamnosylation 218:240 A previously discovered posttranslational modification strategy - arginine rhamnosylation - 152:242 A previously discovered posttranslational modification strategy - arginine rhamnosylation - is essential for elongation factor P (EF-P) dependent rescue of polyproline stalled ribosomes in clinically relevant species such as Pseudomonas aeruginosa and Neisseria meningitidis. 28451135 6 46 theme rhamnosylated 1191:1203 arg1 EF-P 1205:1208 endogenously produced rhamnosylated EF-P 1169:1208 endogenously produced rhamnosylated EF-P 1169:1208 Having the anti-ArgRha at hand we were able to visualize endogenously produced rhamnosylated EF-P. 28451135 0 47 theme translation 61:71 arg1 factor 84:89 arginine-rhamnosylated translation elongation factor 38:89 arginine-rhamnosylated translation elongation factor P 38:91 Resolving the α-glycosidic linkage of arginine-rhamnosylated translation elongation factor P triggers generation of the first ArgRha specific antibody. 28451135 1 48 theme relevant 352:359 arg1 aeruginosa 389:398 Pseudomonas aeruginosa 377:398 Pseudomonas aeruginosa 377:398 A previously discovered posttranslational modification strategy - arginine rhamnosylation - is essential for elongation factor P (EF-P) dependent rescue of polyproline stalled ribosomes in clinically relevant species such as Pseudomonas aeruginosa and Neisseria meningitidis. 28451135 1 48 theme relevant 352:359 arg1 meningitidis 414:425 Neisseria meningitidis 404:425 Neisseria meningitidis 404:425 A previously discovered posttranslational modification strategy - arginine rhamnosylation - is essential for elongation factor P (EF-P) dependent rescue of polyproline stalled ribosomes in clinically relevant species such as Pseudomonas aeruginosa and Neisseria meningitidis. 28451135 1 48 theme relevant 352:359 arg1 species 361:367 clinically relevant species 341:367 clinically relevant species such as Pseudomonas aeruginosa and Neisseria meningitidis 341:425 A previously discovered posttranslational modification strategy - arginine rhamnosylation - is essential for elongation factor P (EF-P) dependent rescue of polyproline stalled ribosomes in clinically relevant species such as Pseudomonas aeruginosa and Neisseria meningitidis. 28451135 2 49 theme glycosylation 493:505 arg1 type 476:479 this new type 467:479 this new type of N-linked glycosylation 467:505 However, almost nothing is known about this new type of N-linked glycosylation. 28451135 3 50 theme rhamnose 602:609 arg1 anomer 592:597 the α anomer 586:597 the α anomer of rhamnose 586:609 In the present study we used NMR spectroscopy to show for the first time that the α anomer of rhamnose is attached to Arg32 of EF-P, demonstrating that the corresponding glycosyltransferase EarP inverts the sugar of its cognate substrate dTDP-β-l-rhamnose. 28451135 6 51 theme produced 1182:1189 arg1 EF-P 1205:1208 endogenously produced rhamnosylated EF-P 1169:1208 endogenously produced rhamnosylated EF-P 1169:1208 Having the anti-ArgRha at hand we were able to visualize endogenously produced rhamnosylated EF-P. 28451135 4 52 theme α-rhamnosylated 819:833 arg1 arginine 835:842 an α-rhamnosylated arginine 816:842 an α-rhamnosylated arginine containing peptide antigen in order to raise the first anti-rhamnosyl arginine specific antibody (anti-ArgRha) 816:953 Based on this finding we describe the synthesis of an α-rhamnosylated arginine containing peptide antigen in order to raise the first anti-rhamnosyl arginine specific antibody (anti-ArgRha). 28451135 3 53 theme present 515:521 arg1 study 523:527 the present study 511:527 the present study 511:527 In the present study we used NMR spectroscopy to show for the first time that the α anomer of rhamnose is attached to Arg32 of EF-P, demonstrating that the corresponding glycosyltransferase EarP inverts the sugar of its cognate substrate dTDP-β-l-rhamnose. 28451135 7 54 dep only 1250:1253 arg1 not 1246:1248 not 1246:1248 not 1246:1248 Thus, we expect the antibody to be not only important to monitor EF-P rhamnosylation in diverse bacteria but also to identify further rhamnosyl arginine containing proteins. 28451135 3 55 theme corresponding 664:676 arg1 EarP 698:701 the corresponding glycosyltransferase EarP 660:701 the corresponding glycosyltransferase EarP 660:701 In the present study we used NMR spectroscopy to show for the first time that the α anomer of rhamnose is attached to Arg32 of EF-P, demonstrating that the corresponding glycosyltransferase EarP inverts the sugar of its cognate substrate dTDP-β-l-rhamnose. 28451135 3 56 theme EF-P 635:638 arg1 Arg32 626:630 Arg32 626:630 Arg32 of EF-P 626:638 In the present study we used NMR spectroscopy to show for the first time that the α anomer of rhamnose is attached to Arg32 of EF-P, demonstrating that the corresponding glycosyltransferase EarP inverts the sugar of its cognate substrate dTDP-β-l-rhamnose. 28451135 5 57 dep demonstrated 997:1008 arg1 Using 956:960 Using 956:960 Using ELISA and Western Blot analyses 956:992 Using ELISA and Western Blot analyses we demonstrated both its high affinity and specificity without any cross-reactivity to other N-glycosylated proteins. 28451135 0 58 theme P 91:91 arg1 linkage 27:33 the α-glycosidic linkage 10:33 the α-glycosidic linkage of arginine-rhamnosylated translation elongation factor P 10:91 Resolving the α-glycosidic linkage of arginine-rhamnosylated translation elongation factor P triggers generation of the first ArgRha specific antibody. 28451135 3 59 theme glycosyltransferase 678:696 arg1 EarP 698:701 the corresponding glycosyltransferase EarP 660:701 the corresponding glycosyltransferase EarP 660:701 In the present study we used NMR spectroscopy to show for the first time that the α anomer of rhamnose is attached to Arg32 of EF-P, demonstrating that the corresponding glycosyltransferase EarP inverts the sugar of its cognate substrate dTDP-β-l-rhamnose. 28451135 4 60 theme arginine 835:842 arg1 synthesis 803:811 the synthesis 799:811 the synthesis of an α-rhamnosylated arginine containing peptide antigen in order to raise the first anti-rhamnosyl arginine specific antibody (anti-ArgRha) 799:953 Based on this finding we describe the synthesis of an α-rhamnosylated arginine containing peptide antigen in order to raise the first anti-rhamnosyl arginine specific antibody (anti-ArgRha). 28451135 7 61 theme diverse 1299:1305 arg1 bacteria 1307:1314 diverse bacteria 1299:1314 diverse bacteria 1299:1314 Thus, we expect the antibody to be not only important to monitor EF-P rhamnosylation in diverse bacteria but also to identify further rhamnosyl arginine containing proteins. 28451135 0 62 theme factor 84:89 arg1 P 91:91 arginine-rhamnosylated translation elongation factor P 38:91 arginine-rhamnosylated translation elongation factor P 38:91 Resolving the α-glycosidic linkage of arginine-rhamnosylated translation elongation factor P triggers generation of the first ArgRha specific antibody. 28451135 2 63 theme new 472:474 arg1 type 476:479 this new type 467:479 this new type of N-linked glycosylation 467:505 However, almost nothing is known about this new type of N-linked glycosylation. 28451135 1 64 theme discovered 165:174 arg1 modification 194:205 A previously discovered posttranslational modification 152:205 A previously discovered posttranslational modification strategy - arginine rhamnosylation - 152:242 A previously discovered posttranslational modification strategy - arginine rhamnosylation - is essential for elongation factor P (EF-P) dependent rescue of polyproline stalled ribosomes in clinically relevant species such as Pseudomonas aeruginosa and Neisseria meningitidis. 28451135 3 65 attach attached 614:621 arg2 anomer 592:597 the α anomer 586:597 the α anomer of rhamnose 586:609 In the present study we used NMR spectroscopy to show for the first time that the α anomer of rhamnose is attached to Arg32 of EF-P, demonstrating that the corresponding glycosyltransferase EarP inverts the sugar of its cognate substrate dTDP-β-l-rhamnose. 28451135 3 65 attach attached 614:621 arg1 Arg32 626:630 Arg32 626:630 Arg32 of EF-P 626:638 In the present study we used NMR spectroscopy to show for the first time that the α anomer of rhamnose is attached to Arg32 of EF-P, demonstrating that the corresponding glycosyltransferase EarP inverts the sugar of its cognate substrate dTDP-β-l-rhamnose. 27315169 1 0 from loss 165:168 arg1 cancer 179:184 human cancer 173:184 human cancer 173:184 p53 is a central factor in tumor suppression as exemplified by its frequent loss in human cancer. 27315169 3 1 theme cell 451:454 arg1 machinery 462:470 the cell death machinery 447:470 the cell death machinery 447:470 The ways in which p53 promotes cell death can involve direct activation or engagement of the cell death machinery, or can be via indirect mechanisms, for example though regulation of ER stress and autophagy. 27315169 3 2 theme death 456:460 arg1 machinery 462:470 the cell death machinery 447:470 the cell death machinery 447:470 The ways in which p53 promotes cell death can involve direct activation or engagement of the cell death machinery, or can be via indirect mechanisms, for example though regulation of ER stress and autophagy. 27315169 8 3 theme cell 1357:1360 arg1 death 1362:1366 programmed cell death 1346:1366 programmed cell death that could potentially be exploited for cancer therapy 1346:1421 In summary, these findings add an additional component to p53s tumor suppressive response and highlight another mechanism by which the tumor suppressor controls programmed cell death that could potentially be exploited for cancer therapy. 27315169 7 4 theme apoptotic 1168:1176 arg1 death 1178:1182 p53-dependent, chemotherapy-induced apoptotic death 1132:1182 p53-dependent, chemotherapy-induced apoptotic death 1132:1182 In this context, while we found that over-expression of FUCA1 does not induce cell death, RNAi-mediated knockdown of endogenous FUCA1 significantly attenuates p53-dependent, chemotherapy-induced apoptotic death. 27315169 2 5 theme cell 319:322 arg1 death 324:328 programmed cell death 308:328 programmed cell death 308:328 p53 exerts its tumor suppressive effects in multiple ways, but the ability to invoke the eradication of damaged cells by programmed cell death is considered a key factor. 27315169 4 6 theme glycosidase 675:685 arg1 FUCA1 688:692 the glycosidase, FUCA1 671:692 FUCA1 688:692 We present here another level of control in p53-mediated tumor suppression by showing that p53 activates the glycosidase, FUCA1, a modulator of N-linked glycosylation. 27315169 4 6 theme glycosidase 675:685 arg1 modulator 697:705 a modulator 695:705 a modulator of N-linked glycosylation 695:731 We present here another level of control in p53-mediated tumor suppression by showing that p53 activates the glycosidase, FUCA1, a modulator of N-linked glycosylation. 27315169 7 7 theme cell 1051:1054 arg1 death 1056:1060 cell death 1051:1060 cell death 1051:1060 In this context, while we found that over-expression of FUCA1 does not induce cell death, RNAi-mediated knockdown of endogenous FUCA1 significantly attenuates p53-dependent, chemotherapy-induced apoptotic death. 27315169 5 8 theme FUCA1 832:836 arg1 up-regulation 838:850 FUCA1 up-regulation 832:850 FUCA1 up-regulation 832:850 We show that p53 transcriptionally activates FUCA1 and that p53 modulates fucosidase activity via FUCA1 up-regulation. 27315169 4 9 from control 599:605 arg1 suppression 629:639 p53-mediated tumor suppression 610:639 p53-mediated tumor suppression by showing that p53 activates the glycosidase, FUCA1, a modulator of N-linked glycosylation 610:731 We present here another level of control in p53-mediated tumor suppression by showing that p53 activates the glycosidase, FUCA1, a modulator of N-linked glycosylation. 27315169 6 10 theme fucosidase 926:935 arg1 activity 937:944 fucosidase activity 926:944 fucosidase activity 926:944 Importantly, we also report that chemotherapeutic drugs induce FUCA1 and fucosidase activity in a p53-dependent manner. 27315169 4 11 theme tumor 623:627 arg1 suppression 629:639 p53-mediated tumor suppression 610:639 p53-mediated tumor suppression by showing that p53 activates the glycosidase, FUCA1, a modulator of N-linked glycosylation 610:731 We present here another level of control in p53-mediated tumor suppression by showing that p53 activates the glycosidase, FUCA1, a modulator of N-linked glycosylation. 27315169 8 12 theme suppressive 1254:1264 arg1 response 1266:1273 p53s tumor suppressive response 1243:1273 p53s tumor suppressive response 1243:1273 In summary, these findings add an additional component to p53s tumor suppressive response and highlight another mechanism by which the tumor suppressor controls programmed cell death that could potentially be exploited for cancer therapy. 27315169 8 13 theme additional 1219:1228 arg1 component 1230:1238 an additional component 1216:1238 an additional component to p53s tumor suppressive response 1216:1273 In summary, these findings add an additional component to p53s tumor suppressive response and highlight another mechanism by which the tumor suppressor controls programmed cell death that could potentially be exploited for cancer therapy. 27315169 4 14 theme control 599:605 arg1 level 590:594 another level 582:594 another level of control in p53-mediated tumor suppression by showing that p53 activates the glycosidase, FUCA1, a modulator of N-linked glycosylation 582:731 We present here another level of control in p53-mediated tumor suppression by showing that p53 activates the glycosidase, FUCA1, a modulator of N-linked glycosylation. 27315169 1 15 theme frequent 156:163 arg1 loss 165:168 its frequent loss 152:168 its frequent loss in human cancer 152:184 p53 is a central factor in tumor suppression as exemplified by its frequent loss in human cancer. 27315169 8 16 theme tumor 1320:1324 arg1 suppressor 1326:1335 the tumor suppressor 1316:1335 the tumor suppressor 1316:1335 In summary, these findings add an additional component to p53s tumor suppressive response and highlight another mechanism by which the tumor suppressor controls programmed cell death that could potentially be exploited for cancer therapy. 27315169 4 17 from level 590:594 arg1 suppression 629:639 p53-mediated tumor suppression 610:639 p53-mediated tumor suppression by showing that p53 activates the glycosidase, FUCA1, a modulator of N-linked glycosylation 610:731 We present here another level of control in p53-mediated tumor suppression by showing that p53 activates the glycosidase, FUCA1, a modulator of N-linked glycosylation. 27315169 8 18 theme programmed 1346:1355 arg1 death 1362:1366 programmed cell death 1346:1366 programmed cell death that could potentially be exploited for cancer therapy 1346:1421 In summary, these findings add an additional component to p53s tumor suppressive response and highlight another mechanism by which the tumor suppressor controls programmed cell death that could potentially be exploited for cancer therapy. 27315169 2 19 theme key 346:348 arg1 factor 350:355 a key factor 344:355 a key factor 344:355 p53 exerts its tumor suppressive effects in multiple ways, but the ability to invoke the eradication of damaged cells by programmed cell death is considered a key factor. 27315169 7 20 theme p53-dependent 1132:1144 arg1 death 1178:1182 p53-dependent, chemotherapy-induced apoptotic death 1132:1182 p53-dependent, chemotherapy-induced apoptotic death 1132:1182 In this context, while we found that over-expression of FUCA1 does not induce cell death, RNAi-mediated knockdown of endogenous FUCA1 significantly attenuates p53-dependent, chemotherapy-induced apoptotic death. 27315169 7 21 theme endogenous 1090:1099 arg1 FUCA1 1101:1105 endogenous FUCA1 1090:1105 endogenous FUCA1 1090:1105 In this context, while we found that over-expression of FUCA1 does not induce cell death, RNAi-mediated knockdown of endogenous FUCA1 significantly attenuates p53-dependent, chemotherapy-induced apoptotic death. 27315169 7 22 theme FUCA1 1029:1033 arg1 over-expression 1010:1024 over-expression 1010:1024 over-expression of FUCA1 1010:1033 In this context, while we found that over-expression of FUCA1 does not induce cell death, RNAi-mediated knockdown of endogenous FUCA1 significantly attenuates p53-dependent, chemotherapy-induced apoptotic death. 27315169 1 23 from factor 106:111 arg1 suppression 122:132 tumor suppression 116:132 tumor suppression 116:132 p53 is a central factor in tumor suppression as exemplified by its frequent loss in human cancer. 27315169 1 24 theme human 173:177 arg1 cancer 179:184 human cancer 173:184 human cancer 173:184 p53 is a central factor in tumor suppression as exemplified by its frequent loss in human cancer. 27315169 7 25 theme FUCA1 1101:1105 arg1 knockdown 1077:1085 RNAi-mediated knockdown 1063:1085 RNAi-mediated knockdown of endogenous FUCA1 1063:1105 In this context, while we found that over-expression of FUCA1 does not induce cell death, RNAi-mediated knockdown of endogenous FUCA1 significantly attenuates p53-dependent, chemotherapy-induced apoptotic death. 27315169 3 26 theme ER 541:542 arg1 stress 544:549 ER stress 541:549 ER stress 541:549 The ways in which p53 promotes cell death can involve direct activation or engagement of the cell death machinery, or can be via indirect mechanisms, for example though regulation of ER stress and autophagy. 27315169 3 27 theme indirect 487:494 arg1 mechanisms 496:505 indirect mechanisms 487:505 indirect mechanisms 487:505 The ways in which p53 promotes cell death can involve direct activation or engagement of the cell death machinery, or can be via indirect mechanisms, for example though regulation of ER stress and autophagy. 27315169 3 28 theme direct 412:417 arg1 activation 419:428 direct activation 412:428 direct activation 412:428 The ways in which p53 promotes cell death can involve direct activation or engagement of the cell death machinery, or can be via indirect mechanisms, for example though regulation of ER stress and autophagy. 27315169 1 29 theme central 98:104 arg1 factor 106:111 a central factor 96:111 a central factor 96:111 p53 is a central factor in tumor suppression as exemplified by its frequent loss in human cancer. 27315169 1 29 theme central 98:104 arg1 p53 89:91 p53 89:91 p53 89:91 p53 is a central factor in tumor suppression as exemplified by its frequent loss in human cancer. 27315169 4 30 theme p53-mediated 610:621 arg1 suppression 629:639 p53-mediated tumor suppression 610:639 p53-mediated tumor suppression by showing that p53 activates the glycosidase, FUCA1, a modulator of N-linked glycosylation 610:731 We present here another level of control in p53-mediated tumor suppression by showing that p53 activates the glycosidase, FUCA1, a modulator of N-linked glycosylation. 27315169 8 31 theme p53s 1243:1246 arg1 response 1266:1273 p53s tumor suppressive response 1243:1273 p53s tumor suppressive response 1243:1273 In summary, these findings add an additional component to p53s tumor suppressive response and highlight another mechanism by which the tumor suppressor controls programmed cell death that could potentially be exploited for cancer therapy. 27315169 5 32 theme fucosidase 808:817 arg1 activity 819:826 fucosidase activity 808:826 fucosidase activity 808:826 We show that p53 transcriptionally activates FUCA1 and that p53 modulates fucosidase activity via FUCA1 up-regulation. 27315169 4 33 link N-linked 710:717 arg1 glycosylation 719:731 N-linked glycosylation 710:731 N-linked glycosylation 710:731 We present here another level of control in p53-mediated tumor suppression by showing that p53 activates the glycosidase, FUCA1, a modulator of N-linked glycosylation. 27315169 3 34 theme cell 389:392 arg1 death 394:398 cell death 389:398 cell death 389:398 The ways in which p53 promotes cell death can involve direct activation or engagement of the cell death machinery, or can be via indirect mechanisms, for example though regulation of ER stress and autophagy. 27315169 6 35 theme chemotherapeutic 886:901 arg1 drugs 903:907 chemotherapeutic drugs 886:907 chemotherapeutic drugs 886:907 Importantly, we also report that chemotherapeutic drugs induce FUCA1 and fucosidase activity in a p53-dependent manner. 27315169 0 36 theme glycosidase 27:37 arg1 FUCA1 39:43 the glycosidase FUCA1 23:43 the glycosidase FUCA1 to promote chemotherapy-induced cell death 23:86 p53 directly regulates the glycosidase FUCA1 to promote chemotherapy-induced cell death. 27315169 2 37 theme suppressive 208:218 arg1 effects 220:226 its tumor suppressive effects 198:226 its tumor suppressive effects 198:226 p53 exerts its tumor suppressive effects in multiple ways, but the ability to invoke the eradication of damaged cells by programmed cell death is considered a key factor. 27315169 7 38 theme RNAi-mediated 1063:1075 arg1 knockdown 1077:1085 RNAi-mediated knockdown 1063:1085 RNAi-mediated knockdown of endogenous FUCA1 1063:1105 In this context, while we found that over-expression of FUCA1 does not induce cell death, RNAi-mediated knockdown of endogenous FUCA1 significantly attenuates p53-dependent, chemotherapy-induced apoptotic death. 27315169 2 39 theme tumor 202:206 arg1 effects 220:226 its tumor suppressive effects 198:226 its tumor suppressive effects 198:226 p53 exerts its tumor suppressive effects in multiple ways, but the ability to invoke the eradication of damaged cells by programmed cell death is considered a key factor. 27315169 2 40 theme programmed 308:317 arg1 death 324:328 programmed cell death 308:328 programmed cell death 308:328 p53 exerts its tumor suppressive effects in multiple ways, but the ability to invoke the eradication of damaged cells by programmed cell death is considered a key factor. 27315169 8 41 theme cancer 1408:1413 arg1 therapy 1415:1421 cancer therapy 1408:1421 cancer therapy 1408:1421 In summary, these findings add an additional component to p53s tumor suppressive response and highlight another mechanism by which the tumor suppressor controls programmed cell death that could potentially be exploited for cancer therapy. 27315169 8 42 theme tumor 1248:1252 arg1 response 1266:1273 p53s tumor suppressive response 1243:1273 p53s tumor suppressive response 1243:1273 In summary, these findings add an additional component to p53s tumor suppressive response and highlight another mechanism by which the tumor suppressor controls programmed cell death that could potentially be exploited for cancer therapy. 27315169 4 43 theme glycosylation 719:731 arg1 FUCA1 688:692 the glycosidase, FUCA1 671:692 FUCA1 688:692 We present here another level of control in p53-mediated tumor suppression by showing that p53 activates the glycosidase, FUCA1, a modulator of N-linked glycosylation. 27315169 4 43 theme glycosylation 719:731 arg1 modulator 697:705 a modulator 695:705 a modulator of N-linked glycosylation 695:731 We present here another level of control in p53-mediated tumor suppression by showing that p53 activates the glycosidase, FUCA1, a modulator of N-linked glycosylation. 27315169 7 44 dep p53-dependent 1132:1144 arg1 chemotherapy-induced 1147:1166 chemotherapy-induced 1147:1166 chemotherapy-induced 1147:1166 In this context, while we found that over-expression of FUCA1 does not induce cell death, RNAi-mediated knockdown of endogenous FUCA1 significantly attenuates p53-dependent, chemotherapy-induced apoptotic death. 27315169 4 45 theme N-linked 710:717 arg1 glycosylation 719:731 N-linked glycosylation 710:731 N-linked glycosylation 710:731 We present here another level of control in p53-mediated tumor suppression by showing that p53 activates the glycosidase, FUCA1, a modulator of N-linked glycosylation. 27315169 1 46 theme tumor 116:120 arg1 suppression 122:132 tumor suppression 116:132 tumor suppression 116:132 p53 is a central factor in tumor suppression as exemplified by its frequent loss in human cancer. 27315169 3 47 theme autophagy 555:563 arg1 regulation 527:536 regulation 527:536 regulation of ER stress and autophagy 527:563 The ways in which p53 promotes cell death can involve direct activation or engagement of the cell death machinery, or can be via indirect mechanisms, for example though regulation of ER stress and autophagy. 27315169 2 48 theme damaged 291:297 arg1 cells 299:303 damaged cells 291:303 damaged cells 291:303 p53 exerts its tumor suppressive effects in multiple ways, but the ability to invoke the eradication of damaged cells by programmed cell death is considered a key factor. 27315169 2 49 theme cells 299:303 arg1 eradication 276:286 the eradication 272:286 the eradication of damaged cells by programmed cell death 272:328 p53 exerts its tumor suppressive effects in multiple ways, but the ability to invoke the eradication of damaged cells by programmed cell death is considered a key factor. 27315169 0 50 theme cell 77:80 arg1 death 82:86 chemotherapy-induced cell death 56:86 chemotherapy-induced cell death 56:86 p53 directly regulates the glycosidase FUCA1 to promote chemotherapy-induced cell death. 27315169 2 51 theme multiple 231:238 arg1 ways 240:243 multiple ways 231:243 multiple ways 231:243 p53 exerts its tumor suppressive effects in multiple ways, but the ability to invoke the eradication of damaged cells by programmed cell death is considered a key factor. 27315169 3 52 theme machinery 462:470 arg1 engagement 433:442 engagement 433:442 engagement of the cell death machinery 433:470 The ways in which p53 promotes cell death can involve direct activation or engagement of the cell death machinery, or can be via indirect mechanisms, for example though regulation of ER stress and autophagy. 27315169 3 52 theme machinery 462:470 arg1 activation 419:428 direct activation 412:428 direct activation 412:428 The ways in which p53 promotes cell death can involve direct activation or engagement of the cell death machinery, or can be via indirect mechanisms, for example though regulation of ER stress and autophagy. 27315169 0 53 theme chemotherapy-induced 56:75 arg1 death 82:86 chemotherapy-induced cell death 56:86 chemotherapy-induced cell death 56:86 p53 directly regulates the glycosidase FUCA1 to promote chemotherapy-induced cell death. 27315169 3 54 theme stress 544:549 arg1 regulation 527:536 regulation 527:536 regulation of ER stress and autophagy 527:563 The ways in which p53 promotes cell death can involve direct activation or engagement of the cell death machinery, or can be via indirect mechanisms, for example though regulation of ER stress and autophagy. 27315169 4 55 from suppression 629:639 arg1 level 590:594 another level 582:594 another level of control in p53-mediated tumor suppression by showing that p53 activates the glycosidase, FUCA1, a modulator of N-linked glycosylation 582:731 We present here another level of control in p53-mediated tumor suppression by showing that p53 activates the glycosidase, FUCA1, a modulator of N-linked glycosylation. 27315169 6 56 theme p53-dependent 951:963 arg1 manner 965:970 a p53-dependent manner 949:970 a p53-dependent manner 949:970 Importantly, we also report that chemotherapeutic drugs induce FUCA1 and fucosidase activity in a p53-dependent manner. 27157597 0 0 theme antiviral 62:70 arg1 IFNa 0:3 IFNa 0:3 IFNa of triploid hybrid of gold fish and allotetraploid 0:54 IFNa of triploid hybrid of gold fish and allotetraploid is an antiviral cytokine against SVCV and GCRV. 27157597 0 0 theme antiviral 62:70 arg1 cytokine 72:79 an antiviral cytokine 59:79 an antiviral cytokine against SVCV and GCRV 59:101 IFNa of triploid hybrid of gold fish and allotetraploid is an antiviral cytokine against SVCV and GCRV. 27157597 1 1 theme fish 128:131 arg1 hybrid 113:118 Triploid hybrid 104:118 Triploid hybrid of gold fish (Carassius auratus red var., ♀, 2n = 100) and allotetroploid (♂, 2n = 100) 104:206 Triploid hybrid of gold fish (Carassius auratus red var., ♀, 2n = 100) and allotetroploid (♂, 2n = 100) displays much improved disease resistance than its parents. 27157597 6 2 theme signal 893:898 arg1 peptide 900:906 the N-terminal signal peptide 878:906 the N-terminal signal peptide 878:906 It is interesting that the pre-matured 3nIFNa is modified with N-linked glycosylation, which is located within the N-terminal signal peptide. 27157597 6 3 theme pre-matured 794:804 arg1 3nIFNa 806:811 the pre-matured 3nIFNa 790:811 the pre-matured 3nIFNa 790:811 It is interesting that the pre-matured 3nIFNa is modified with N-linked glycosylation, which is located within the N-terminal signal peptide. 27157597 3 4 theme predicted 436:444 arg1 protein 453:459 the predicted 3nIFNa protein 432:459 the predicted 3nIFNa protein 432:459 The full-length cDNA of 3nIFNa consists of 740 nucleotides and the predicted 3nIFNa protein contains 183 amino acids. 27157597 4 5 theme mRNA 491:494 arg1 transcription 496:508 The mRNA transcription 487:508 The mRNA transcription of 3nIFNa 487:518 The mRNA transcription of 3nIFNa was detected in all the selected tissues of triploid hybrid and was obviously enhanced after SVCV or GCRV infection. 27157597 7 6 theme control 1156:1162 arg1 cells 1168:1172 the control EPC cells 1152:1172 the control EPC cells 1152:1172 EPC cells showed much-decreased cytopathic effect when treated with 3nIFNa-containing media or transfected with plasmid expressing 3nIFNa at 24 h before SVCV or GCRV infection; and the virus titers in these cells were much lower than those of the control EPC cells. 27157597 8 7 theme above 1183:1187 arg1 data 1189:1192 All the above data 1175:1192 All the above data 1175:1192 All the above data support the conclusion that 3nIFNa is a secreted cytokine functioning in host innate immune response against virus invasion. 27157597 3 8 theme 3nIFNa 446:451 arg1 protein 453:459 the predicted 3nIFNa protein 432:459 the predicted 3nIFNa protein 432:459 The full-length cDNA of 3nIFNa consists of 740 nucleotides and the predicted 3nIFNa protein contains 183 amino acids. 27157597 7 9 theme EPC 1164:1166 arg1 cells 1168:1172 the control EPC cells 1152:1172 the control EPC cells 1152:1172 EPC cells showed much-decreased cytopathic effect when treated with 3nIFNa-containing media or transfected with plasmid expressing 3nIFNa at 24 h before SVCV or GCRV infection; and the virus titers in these cells were much lower than those of the control EPC cells. 27157597 7 10 theme virus 1094:1098 arg1 titers 1100:1105 the virus titers 1090:1105 the virus titers in these cells 1090:1120 EPC cells showed much-decreased cytopathic effect when treated with 3nIFNa-containing media or transfected with plasmid expressing 3nIFNa at 24 h before SVCV or GCRV infection; and the virus titers in these cells were much lower than those of the control EPC cells. 27157597 7 10 theme virus 1094:1098 arg1 lower 1132:1136 lower 1132:1136 lower 1132:1136 EPC cells showed much-decreased cytopathic effect when treated with 3nIFNa-containing media or transfected with plasmid expressing 3nIFNa at 24 h before SVCV or GCRV infection; and the virus titers in these cells were much lower than those of the control EPC cells. 27157597 8 11 theme secreted 1234:1241 arg1 3nIFNa 1222:1227 3nIFNa 1222:1227 3nIFNa 1222:1227 All the above data support the conclusion that 3nIFNa is a secreted cytokine functioning in host innate immune response against virus invasion. 27157597 8 11 theme secreted 1234:1241 arg1 cytokine 1243:1250 a secreted cytokine 1232:1250 a secreted cytokine functioning in host innate immune response against virus invasion 1232:1316 All the above data support the conclusion that 3nIFNa is a secreted cytokine functioning in host innate immune response against virus invasion. 27157597 2 12 theme I 299:299 arg1 IFNs 301:304 the type I IFNs 290:304 the type I IFNs of triploid hybrid (3nIFNa) 290:332 In this paper, one of the type I IFNs of triploid hybrid (3nIFNa) has been cloned and characterized. 27157597 1 13 theme Carassius 134:142 arg1 ♀ 162:162 ♀ 162:162 ♀ 162:162 Triploid hybrid of gold fish (Carassius auratus red var., ♀, 2n = 100) and allotetroploid (♂, 2n = 100) displays much improved disease resistance than its parents. 27157597 1 13 theme Carassius 134:142 arg1 var. 156:159 Carassius auratus red var. 134:159 Carassius auratus red var. 134:159 Triploid hybrid of gold fish (Carassius auratus red var., ♀, 2n = 100) and allotetroploid (♂, 2n = 100) displays much improved disease resistance than its parents. 27157597 1 13 theme Carassius 134:142 arg1 2n = 100 165:172 2n = 100 165:172 2n = 100 165:172 Triploid hybrid of gold fish (Carassius auratus red var., ♀, 2n = 100) and allotetroploid (♂, 2n = 100) displays much improved disease resistance than its parents. 27157597 5 14 theme whole 665:669 arg1 lysate 676:681 whole cell lysate 665:681 whole cell lysate 665:681 bcIFNa was detected in both whole cell lysate and supernatant media of HEK293T cells transfected with plasmids expressing bcIFNa. 27157597 2 15 theme IFNs 301:304 arg1 IFNs 301:304 the type I IFNs 290:304 the type I IFNs of triploid hybrid (3nIFNa) 290:332 In this paper, one of the type I IFNs of triploid hybrid (3nIFNa) has been cloned and characterized. 27157597 2 15 theme IFNs 301:304 arg1 one 283:285 one 283:285 one 283:285 In this paper, one of the type I IFNs of triploid hybrid (3nIFNa) has been cloned and characterized. 27157597 5 16 theme supernatant 687:697 arg1 media 699:703 supernatant media 687:703 supernatant media 687:703 bcIFNa was detected in both whole cell lysate and supernatant media of HEK293T cells transfected with plasmids expressing bcIFNa. 27157597 1 17 dep fish 128:131 arg1 ♀ 162:162 ♀ 162:162 ♀ 162:162 Triploid hybrid of gold fish (Carassius auratus red var., ♀, 2n = 100) and allotetroploid (♂, 2n = 100) displays much improved disease resistance than its parents. 27157597 1 17 dep fish 128:131 arg1 var. 156:159 Carassius auratus red var. 134:159 Carassius auratus red var. 134:159 Triploid hybrid of gold fish (Carassius auratus red var., ♀, 2n = 100) and allotetroploid (♂, 2n = 100) displays much improved disease resistance than its parents. 27157597 1 17 dep fish 128:131 arg1 2n = 100 165:172 2n = 100 165:172 2n = 100 165:172 Triploid hybrid of gold fish (Carassius auratus red var., ♀, 2n = 100) and allotetroploid (♂, 2n = 100) displays much improved disease resistance than its parents. 27157597 1 18 theme red 152:154 arg1 ♀ 162:162 ♀ 162:162 ♀ 162:162 Triploid hybrid of gold fish (Carassius auratus red var., ♀, 2n = 100) and allotetroploid (♂, 2n = 100) displays much improved disease resistance than its parents. 27157597 1 18 theme red 152:154 arg1 var. 156:159 Carassius auratus red var. 134:159 Carassius auratus red var. 134:159 Triploid hybrid of gold fish (Carassius auratus red var., ♀, 2n = 100) and allotetroploid (♂, 2n = 100) displays much improved disease resistance than its parents. 27157597 1 18 theme red 152:154 arg1 2n = 100 165:172 2n = 100 165:172 2n = 100 165:172 Triploid hybrid of gold fish (Carassius auratus red var., ♀, 2n = 100) and allotetroploid (♂, 2n = 100) displays much improved disease resistance than its parents. 27157597 3 19 contain contains 461:468 arg2 acids 480:484 183 amino acids 470:484 183 amino acids 470:484 The full-length cDNA of 3nIFNa consists of 740 nucleotides and the predicted 3nIFNa protein contains 183 amino acids. 27157597 3 19 contain contains 461:468 arg1 protein 453:459 the predicted 3nIFNa protein 432:459 the predicted 3nIFNa protein 432:459 The full-length cDNA of 3nIFNa consists of 740 nucleotides and the predicted 3nIFNa protein contains 183 amino acids. 27157597 3 20 theme amino 474:478 arg1 acids 480:484 183 amino acids 470:484 183 amino acids 470:484 The full-length cDNA of 3nIFNa consists of 740 nucleotides and the predicted 3nIFNa protein contains 183 amino acids. 27157597 2 21 theme type 294:297 arg1 IFNs 301:304 the type I IFNs 290:304 the type I IFNs of triploid hybrid (3nIFNa) 290:332 In this paper, one of the type I IFNs of triploid hybrid (3nIFNa) has been cloned and characterized. 27157597 0 22 theme hybrid 17:22 arg1 IFNa 0:3 IFNa 0:3 IFNa of triploid hybrid of gold fish and allotetraploid 0:54 IFNa of triploid hybrid of gold fish and allotetraploid is an antiviral cytokine against SVCV and GCRV. 27157597 0 22 theme hybrid 17:22 arg1 cytokine 72:79 an antiviral cytokine 59:79 an antiviral cytokine against SVCV and GCRV 59:101 IFNa of triploid hybrid of gold fish and allotetraploid is an antiviral cytokine against SVCV and GCRV. 27157597 4 23 theme GCRV 621:624 arg1 infection 626:634 GCRV infection 621:634 GCRV infection 621:634 The mRNA transcription of 3nIFNa was detected in all the selected tissues of triploid hybrid and was obviously enhanced after SVCV or GCRV infection. 27157597 7 24 theme 3nIFNa-containing 977:993 arg1 media 995:999 3nIFNa-containing media 977:999 3nIFNa-containing media 977:999 EPC cells showed much-decreased cytopathic effect when treated with 3nIFNa-containing media or transfected with plasmid expressing 3nIFNa at 24 h before SVCV or GCRV infection; and the virus titers in these cells were much lower than those of the control EPC cells. 27157597 8 25 theme host 1267:1270 arg1 response 1286:1293 host innate immune response 1267:1293 host innate immune response against virus invasion 1267:1316 All the above data support the conclusion that 3nIFNa is a secreted cytokine functioning in host innate immune response against virus invasion. 27157597 5 26 theme cells 716:720 arg1 lysate 676:681 whole cell lysate 665:681 whole cell lysate 665:681 bcIFNa was detected in both whole cell lysate and supernatant media of HEK293T cells transfected with plasmids expressing bcIFNa. 27157597 5 26 theme cells 716:720 arg1 media 699:703 supernatant media 687:703 supernatant media 687:703 bcIFNa was detected in both whole cell lysate and supernatant media of HEK293T cells transfected with plasmids expressing bcIFNa. 27157597 0 27 theme triploid 8:15 arg1 hybrid 17:22 triploid hybrid 8:22 triploid hybrid of gold fish and allotetraploid 8:54 IFNa of triploid hybrid of gold fish and allotetraploid is an antiviral cytokine against SVCV and GCRV. 27157597 1 28 theme improved 222:229 arg1 resistance 239:248 much improved disease resistance 217:248 much improved disease resistance than its parents 217:265 Triploid hybrid of gold fish (Carassius auratus red var., ♀, 2n = 100) and allotetroploid (♂, 2n = 100) displays much improved disease resistance than its parents. 27157597 1 29 dep allotetroploid 179:192 arg1 ♂ 195:195 ♂ 195:195 ♂ 195:195 Triploid hybrid of gold fish (Carassius auratus red var., ♀, 2n = 100) and allotetroploid (♂, 2n = 100) displays much improved disease resistance than its parents. 27157597 7 30 theme GCRV 1070:1073 arg1 infection 1075:1083 GCRV infection 1070:1083 GCRV infection 1070:1083 EPC cells showed much-decreased cytopathic effect when treated with 3nIFNa-containing media or transfected with plasmid expressing 3nIFNa at 24 h before SVCV or GCRV infection; and the virus titers in these cells were much lower than those of the control EPC cells. 27157597 0 31 theme gold 27:30 arg1 fish 32:35 gold fish 27:35 gold fish 27:35 IFNa of triploid hybrid of gold fish and allotetraploid is an antiviral cytokine against SVCV and GCRV. 27157597 1 32 theme disease 231:237 arg1 resistance 239:248 much improved disease resistance 217:248 much improved disease resistance than its parents 217:265 Triploid hybrid of gold fish (Carassius auratus red var., ♀, 2n = 100) and allotetroploid (♂, 2n = 100) displays much improved disease resistance than its parents. 27157597 7 33 from titers 1100:1105 arg1 cells 1116:1120 these cells 1110:1120 these cells 1110:1120 EPC cells showed much-decreased cytopathic effect when treated with 3nIFNa-containing media or transfected with plasmid expressing 3nIFNa at 24 h before SVCV or GCRV infection; and the virus titers in these cells were much lower than those of the control EPC cells. 27157597 8 34 theme immune 1279:1284 arg1 response 1286:1293 host innate immune response 1267:1293 host innate immune response against virus invasion 1267:1316 All the above data support the conclusion that 3nIFNa is a secreted cytokine functioning in host innate immune response against virus invasion. 27157597 2 35 theme hybrid 318:323 arg1 IFNs 301:304 the type I IFNs 290:304 the type I IFNs of triploid hybrid (3nIFNa) 290:332 In this paper, one of the type I IFNs of triploid hybrid (3nIFNa) has been cloned and characterized. 27157597 5 36 theme cell 671:674 arg1 lysate 676:681 whole cell lysate 665:681 whole cell lysate 665:681 bcIFNa was detected in both whole cell lysate and supernatant media of HEK293T cells transfected with plasmids expressing bcIFNa. 27157597 6 37 mod modified 816:823 arg1 3nIFNa 806:811 the pre-matured 3nIFNa 790:811 the pre-matured 3nIFNa 790:811 It is interesting that the pre-matured 3nIFNa is modified with N-linked glycosylation, which is located within the N-terminal signal peptide. 27157597 6 37 mod modified 816:823 arg3 glycosylation 839:851 N-linked glycosylation 830:851 N-linked glycosylation 830:851 It is interesting that the pre-matured 3nIFNa is modified with N-linked glycosylation, which is located within the N-terminal signal peptide. 27157597 8 38 theme innate 1272:1277 arg1 response 1286:1293 host innate immune response 1267:1293 host innate immune response against virus invasion 1267:1316 All the above data support the conclusion that 3nIFNa is a secreted cytokine functioning in host innate immune response against virus invasion. 27157597 5 39 located detected 648:655 arg1 lysate 676:681 whole cell lysate 665:681 whole cell lysate 665:681 bcIFNa was detected in both whole cell lysate and supernatant media of HEK293T cells transfected with plasmids expressing bcIFNa. 27157597 5 39 located detected 648:655 arg1 media 699:703 supernatant media 687:703 supernatant media 687:703 bcIFNa was detected in both whole cell lysate and supernatant media of HEK293T cells transfected with plasmids expressing bcIFNa. 27157597 5 39 located detected 648:655 arg2 bcIFNa 637:642 bcIFNa 637:642 bcIFNa 637:642 bcIFNa was detected in both whole cell lysate and supernatant media of HEK293T cells transfected with plasmids expressing bcIFNa. 27157597 2 40 theme triploid 309:316 arg1 hybrid 318:323 triploid hybrid 309:323 triploid hybrid (3nIFNa) 309:332 In this paper, one of the type I IFNs of triploid hybrid (3nIFNa) has been cloned and characterized. 27157597 2 40 theme triploid 309:316 arg1 3nIFNa 326:331 3nIFNa 326:331 3nIFNa 326:331 In this paper, one of the type I IFNs of triploid hybrid (3nIFNa) has been cloned and characterized. 27157597 4 41 theme triploid 564:571 arg1 hybrid 573:578 triploid hybrid 564:578 triploid hybrid 564:578 The mRNA transcription of 3nIFNa was detected in all the selected tissues of triploid hybrid and was obviously enhanced after SVCV or GCRV infection. 27157597 1 42 dep Carassius 134:142 arg1 auratus 144:150 auratus 144:150 auratus 144:150 Triploid hybrid of gold fish (Carassius auratus red var., ♀, 2n = 100) and allotetroploid (♂, 2n = 100) displays much improved disease resistance than its parents. 27157597 0 43 theme fish 32:35 arg1 hybrid 17:22 triploid hybrid 8:22 triploid hybrid of gold fish and allotetraploid 8:54 IFNa of triploid hybrid of gold fish and allotetraploid is an antiviral cytokine against SVCV and GCRV. 27157597 6 44 theme N-linked 830:837 arg1 glycosylation 839:851 N-linked glycosylation 830:851 N-linked glycosylation 830:851 It is interesting that the pre-matured 3nIFNa is modified with N-linked glycosylation, which is located within the N-terminal signal peptide. 27157597 4 45 located detected 524:531 arg1 tissues 553:559 all the selected tissues 536:559 all the selected tissues of triploid hybrid 536:578 The mRNA transcription of 3nIFNa was detected in all the selected tissues of triploid hybrid and was obviously enhanced after SVCV or GCRV infection. 27157597 4 45 located detected 524:531 arg2 transcription 496:508 The mRNA transcription 487:508 The mRNA transcription of 3nIFNa 487:518 The mRNA transcription of 3nIFNa was detected in all the selected tissues of triploid hybrid and was obviously enhanced after SVCV or GCRV infection. 27157597 3 46 theme 3nIFNa 393:398 arg1 cDNA 385:388 The full-length cDNA 369:388 The full-length cDNA of 3nIFNa 369:398 The full-length cDNA of 3nIFNa consists of 740 nucleotides and the predicted 3nIFNa protein contains 183 amino acids. 27157597 7 47 theme much-decreased 926:939 arg1 effect 952:957 much-decreased cytopathic effect 926:957 much-decreased cytopathic effect 926:957 EPC cells showed much-decreased cytopathic effect when treated with 3nIFNa-containing media or transfected with plasmid expressing 3nIFNa at 24 h before SVCV or GCRV infection; and the virus titers in these cells were much lower than those of the control EPC cells. 27157597 6 48 located located 863:869 arg1 peptide 900:906 the N-terminal signal peptide 878:906 the N-terminal signal peptide 878:906 It is interesting that the pre-matured 3nIFNa is modified with N-linked glycosylation, which is located within the N-terminal signal peptide. 27157597 6 48 located located 863:869 arg2 glycosylation 839:851 N-linked glycosylation 830:851 N-linked glycosylation 830:851 It is interesting that the pre-matured 3nIFNa is modified with N-linked glycosylation, which is located within the N-terminal signal peptide. 27157597 6 49 link N-linked 830:837 arg1 glycosylation 839:851 N-linked glycosylation 830:851 N-linked glycosylation 830:851 It is interesting that the pre-matured 3nIFNa is modified with N-linked glycosylation, which is located within the N-terminal signal peptide. 27157597 7 50 theme EPC 909:911 arg1 cells 913:917 EPC cells 909:917 EPC cells 909:917 EPC cells showed much-decreased cytopathic effect when treated with 3nIFNa-containing media or transfected with plasmid expressing 3nIFNa at 24 h before SVCV or GCRV infection; and the virus titers in these cells were much lower than those of the control EPC cells. 27157597 1 51 theme Triploid 104:111 arg1 hybrid 113:118 Triploid hybrid 104:118 Triploid hybrid of gold fish (Carassius auratus red var., ♀, 2n = 100) and allotetroploid (♂, 2n = 100) 104:206 Triploid hybrid of gold fish (Carassius auratus red var., ♀, 2n = 100) and allotetroploid (♂, 2n = 100) displays much improved disease resistance than its parents. 27157597 6 52 theme N-terminal 882:891 arg1 peptide 900:906 the N-terminal signal peptide 878:906 the N-terminal signal peptide 878:906 It is interesting that the pre-matured 3nIFNa is modified with N-linked glycosylation, which is located within the N-terminal signal peptide. 27157597 7 53 theme cytopathic 941:950 arg1 effect 952:957 much-decreased cytopathic effect 926:957 much-decreased cytopathic effect 926:957 EPC cells showed much-decreased cytopathic effect when treated with 3nIFNa-containing media or transfected with plasmid expressing 3nIFNa at 24 h before SVCV or GCRV infection; and the virus titers in these cells were much lower than those of the control EPC cells. 27157597 8 54 theme virus 1303:1307 arg1 invasion 1309:1316 virus invasion 1303:1316 virus invasion 1303:1316 All the above data support the conclusion that 3nIFNa is a secreted cytokine functioning in host innate immune response against virus invasion. 27157597 4 55 theme hybrid 573:578 arg1 tissues 553:559 all the selected tissues 536:559 all the selected tissues of triploid hybrid 536:578 The mRNA transcription of 3nIFNa was detected in all the selected tissues of triploid hybrid and was obviously enhanced after SVCV or GCRV infection. 27157597 3 56 theme full-length 373:383 arg1 cDNA 385:388 The full-length cDNA 369:388 The full-length cDNA of 3nIFNa 369:398 The full-length cDNA of 3nIFNa consists of 740 nucleotides and the predicted 3nIFNa protein contains 183 amino acids. 27157597 4 57 theme selected 544:551 arg1 tissues 553:559 all the selected tissues 536:559 all the selected tissues of triploid hybrid 536:578 The mRNA transcription of 3nIFNa was detected in all the selected tissues of triploid hybrid and was obviously enhanced after SVCV or GCRV infection. 27157597 1 58 theme allotetroploid 179:192 arg1 hybrid 113:118 Triploid hybrid 104:118 Triploid hybrid of gold fish (Carassius auratus red var., ♀, 2n = 100) and allotetroploid (♂, 2n = 100) 104:206 Triploid hybrid of gold fish (Carassius auratus red var., ♀, 2n = 100) and allotetroploid (♂, 2n = 100) displays much improved disease resistance than its parents. 27157597 0 59 theme allotetraploid 41:54 arg1 hybrid 17:22 triploid hybrid 8:22 triploid hybrid of gold fish and allotetraploid 8:54 IFNa of triploid hybrid of gold fish and allotetraploid is an antiviral cytokine against SVCV and GCRV. 27157597 5 60 theme HEK293T 708:714 arg1 cells 716:720 HEK293T cells 708:720 HEK293T cells transfected with plasmids expressing bcIFNa 708:764 bcIFNa was detected in both whole cell lysate and supernatant media of HEK293T cells transfected with plasmids expressing bcIFNa. 27157597 1 61 theme gold 123:126 arg1 fish 128:131 gold fish 123:131 gold fish (Carassius auratus red var., ♀, 2n = 100) 123:173 Triploid hybrid of gold fish (Carassius auratus red var., ♀, 2n = 100) and allotetroploid (♂, 2n = 100) displays much improved disease resistance than its parents. 27157597 4 62 theme 3nIFNa 513:518 arg1 transcription 496:508 The mRNA transcription 487:508 The mRNA transcription of 3nIFNa 487:518 The mRNA transcription of 3nIFNa was detected in all the selected tissues of triploid hybrid and was obviously enhanced after SVCV or GCRV infection. 27012235 8 0 theme other 1452:1456 arg1 enzymes 1458:1464 other enzymes 1452:1464 other enzymes 1452:1464 In conclusion, we obtained the thermostability-improved enzyme N84S mutant, and the strategy used to design this mutant based on its structural information and N-linked glycosylation modification could be applied to engineer other enzymes to meet the needs of the biotechnological industry. 27012235 4 1 theme potential 661:669 arg1 sites 687:691 its potential N-glycosylation sites 657:691 its potential N-glycosylation sites (Asn-Xaa-Ser/Thr consensus sequences) 657:729 Subsequently, glycosylation site-directed mutations (A73S, N84S, and R104S) were introduced within the Ω-loop region and its wing chain based on its potential N-glycosylation sites (Asn-Xaa-Ser/Thr consensus sequences) and structure information to improve the thermostability of trypsin. 27012235 4 1 theme potential 661:669 arg1 sequences 720:728 Asn-Xaa-Ser/Thr consensus sequences 694:728 Asn-Xaa-Ser/Thr consensus sequences 694:728 Subsequently, glycosylation site-directed mutations (A73S, N84S, and R104S) were introduced within the Ω-loop region and its wing chain based on its potential N-glycosylation sites (Asn-Xaa-Ser/Thr consensus sequences) and structure information to improve the thermostability of trypsin. 27012235 1 2 theme flexible 142:149 arg1 Ω-loop 115:120 The Ω-loop 111:120 The Ω-loop 111:120 The Ω-loop is a nonregular and flexible structure that plays an important role in molecular recognition, protein folding, and thermostability. 27012235 1 2 theme flexible 142:149 arg1 structure 151:159 a nonregular and flexible structure 125:159 a nonregular and flexible structure that plays an important role in molecular recognition, protein folding, and thermostability 125:251 The Ω-loop is a nonregular and flexible structure that plays an important role in molecular recognition, protein folding, and thermostability. 27012235 8 3 theme N-linked 1387:1394 arg1 glycosylation 1396:1408 N-linked glycosylation 1387:1408 N-linked glycosylation 1387:1408 In conclusion, we obtained the thermostability-improved enzyme N84S mutant, and the strategy used to design this mutant based on its structural information and N-linked glycosylation modification could be applied to engineer other enzymes to meet the needs of the biotechnological industry. 27012235 8 4 theme enzyme 1283:1288 arg1 mutant 1295:1300 the thermostability-improved enzyme N84S mutant 1254:1300 the thermostability-improved enzyme N84S mutant 1254:1300 In conclusion, we obtained the thermostability-improved enzyme N84S mutant, and the strategy used to design this mutant based on its structural information and N-linked glycosylation modification could be applied to engineer other enzymes to meet the needs of the biotechnological industry. 27012235 0 5 theme Ω-Loop 96:101 arg1 Region 103:108 the Ω-Loop Region 92:108 the Ω-Loop Region 92:108 A Novel Strategy for Thermostability Improvement of Trypsin Based on N-Glycosylation within the Ω-Loop Region. 27012235 5 6 theme wildtype 924:931 arg1 enzyme 933:938 the wildtype enzyme 920:938 the wildtype enzyme 920:938 The result demonstrated that the halflife of the N84S mutant at 50°C increased by 177.89 min when compared with that of the wildtype enzyme. 27012235 6 7 theme significant 958:968 arg1 increase 970:977 the significant increase 954:977 the significant increase in the thermal stability of the N84S mutant 954:1021 Furthermore, the significant increase in the thermal stability of the N84S mutant has also been proven by an increase in the Tm values determined by circular dichroism. 27012235 7 8 theme enzyme 1166:1171 arg1 mutant 1186:1191 the N84S mutant 1177:1191 the N84S mutant 1177:1191 Additionally, the optimum temperatures of the wild-type enzyme and the N84S mutant were 75°C and 80°C, respectively. 27012235 7 8 theme enzyme 1166:1171 arg1 75°C 1198:1201 75°C 1198:1201 75°C 1198:1201 Additionally, the optimum temperatures of the wild-type enzyme and the N84S mutant were 75°C and 80°C, respectively. 27012235 7 8 theme enzyme 1166:1171 arg1 temperatures 1136:1147 the optimum temperatures 1124:1147 the optimum temperatures of the wild-type enzyme 1124:1171 Additionally, the optimum temperatures of the wild-type enzyme and the N84S mutant were 75°C and 80°C, respectively. 27012235 4 9 theme structure 735:743 arg1 information 745:755 structure information 735:755 structure information to improve the thermostability of trypsin 735:797 Subsequently, glycosylation site-directed mutations (A73S, N84S, and R104S) were introduced within the Ω-loop region and its wing chain based on its potential N-glycosylation sites (Asn-Xaa-Ser/Thr consensus sequences) and structure information to improve the thermostability of trypsin. 27012235 5 10 from 50°C 864:867 arg1 halflife 833:840 the halflife 829:840 the halflife of the N84S mutant at 50°C 829:867 The result demonstrated that the halflife of the N84S mutant at 50°C increased by 177.89 min when compared with that of the wildtype enzyme. 27012235 2 11 theme molecular 336:344 arg1 profile 372:378 the molecular stability and flexibility profile 332:378 the molecular stability and flexibility profile of the porcine trypsin structures 332:412 In the present study, molecular dynamics simulation was carried out to assess the molecular stability and flexibility profile of the porcine trypsin structures. 27012235 6 12 theme mutant 1016:1021 arg1 stability 994:1002 the thermal stability 982:1002 the thermal stability of the N84S mutant 982:1021 Furthermore, the significant increase in the thermal stability of the N84S mutant has also been proven by an increase in the Tm values determined by circular dichroism. 27012235 2 13 theme present 261:267 arg1 study 269:273 the present study 257:273 the present study 257:273 In the present study, molecular dynamics simulation was carried out to assess the molecular stability and flexibility profile of the porcine trypsin structures. 27012235 8 14 theme N84S 1290:1293 arg1 mutant 1295:1300 the thermostability-improved enzyme N84S mutant 1254:1300 the thermostability-improved enzyme N84S mutant 1254:1300 In conclusion, we obtained the thermostability-improved enzyme N84S mutant, and the strategy used to design this mutant based on its structural information and N-linked glycosylation modification could be applied to engineer other enzymes to meet the needs of the biotechnological industry. 27012235 4 15 dep mutations 554:562 arg1 mutations 554:562 glycosylation site-directed mutations 526:562 glycosylation site-directed mutations (A73S, N84S, and R104S) 526:586 Subsequently, glycosylation site-directed mutations (A73S, N84S, and R104S) were introduced within the Ω-loop region and its wing chain based on its potential N-glycosylation sites (Asn-Xaa-Ser/Thr consensus sequences) and structure information to improve the thermostability of trypsin. 27012235 4 15 dep mutations 554:562 arg1 N84S 571:574 N84S 571:574 N84S 571:574 Subsequently, glycosylation site-directed mutations (A73S, N84S, and R104S) were introduced within the Ω-loop region and its wing chain based on its potential N-glycosylation sites (Asn-Xaa-Ser/Thr consensus sequences) and structure information to improve the thermostability of trypsin. 27012235 4 15 dep mutations 554:562 arg1 R104S 581:585 R104S 581:585 R104S 581:585 Subsequently, glycosylation site-directed mutations (A73S, N84S, and R104S) were introduced within the Ω-loop region and its wing chain based on its potential N-glycosylation sites (Asn-Xaa-Ser/Thr consensus sequences) and structure information to improve the thermostability of trypsin. 27012235 4 15 dep mutations 554:562 arg1 A73S 565:568 A73S 565:568 A73S 565:568 Subsequently, glycosylation site-directed mutations (A73S, N84S, and R104S) were introduced within the Ω-loop region and its wing chain based on its potential N-glycosylation sites (Asn-Xaa-Ser/Thr consensus sequences) and structure information to improve the thermostability of trypsin. 27012235 3 16 theme fragment 428:435 arg1 57-67 437:441 fragment 57-67 428:441 fragment 57-67 428:441 Two Ω-Loops (fragment 57-67 and fragment 78-91) were confirmed to represent the flexible region. 27012235 0 17 theme Novel 2:6 arg1 Strategy 8:15 A Novel Strategy 0:15 A Novel Strategy for Thermostability Improvement of Trypsin 0:58 A Novel Strategy for Thermostability Improvement of Trypsin Based on N-Glycosylation within the Ω-Loop Region. 27012235 8 18 link N-linked 1387:1394 arg1 glycosylation 1396:1408 N-linked glycosylation 1387:1408 N-linked glycosylation 1387:1408 In conclusion, we obtained the thermostability-improved enzyme N84S mutant, and the strategy used to design this mutant based on its structural information and N-linked glycosylation modification could be applied to engineer other enzymes to meet the needs of the biotechnological industry. 27012235 7 19 theme optimum 1128:1134 arg1 75°C 1198:1201 75°C 1198:1201 75°C 1198:1201 Additionally, the optimum temperatures of the wild-type enzyme and the N84S mutant were 75°C and 80°C, respectively. 27012235 7 19 theme optimum 1128:1134 arg1 temperatures 1136:1147 the optimum temperatures 1124:1147 the optimum temperatures of the wild-type enzyme 1124:1171 Additionally, the optimum temperatures of the wild-type enzyme and the N84S mutant were 75°C and 80°C, respectively. 27012235 5 20 theme mutant 854:859 arg1 halflife 833:840 the halflife 829:840 the halflife of the N84S mutant at 50°C 829:867 The result demonstrated that the halflife of the N84S mutant at 50°C increased by 177.89 min when compared with that of the wildtype enzyme. 27012235 6 21 from increase 970:977 arg1 stability 994:1002 the thermal stability 982:1002 the thermal stability of the N84S mutant 982:1021 Furthermore, the significant increase in the thermal stability of the N84S mutant has also been proven by an increase in the Tm values determined by circular dichroism. 27012235 4 22 theme consensus 710:718 arg1 sites 687:691 its potential N-glycosylation sites 657:691 its potential N-glycosylation sites (Asn-Xaa-Ser/Thr consensus sequences) 657:729 Subsequently, glycosylation site-directed mutations (A73S, N84S, and R104S) were introduced within the Ω-loop region and its wing chain based on its potential N-glycosylation sites (Asn-Xaa-Ser/Thr consensus sequences) and structure information to improve the thermostability of trypsin. 27012235 4 22 theme consensus 710:718 arg1 sequences 720:728 Asn-Xaa-Ser/Thr consensus sequences 694:728 Asn-Xaa-Ser/Thr consensus sequences 694:728 Subsequently, glycosylation site-directed mutations (A73S, N84S, and R104S) were introduced within the Ω-loop region and its wing chain based on its potential N-glycosylation sites (Asn-Xaa-Ser/Thr consensus sequences) and structure information to improve the thermostability of trypsin. 27012235 2 23 theme flexibility 360:370 arg1 profile 372:378 the molecular stability and flexibility profile 332:378 the molecular stability and flexibility profile of the porcine trypsin structures 332:412 In the present study, molecular dynamics simulation was carried out to assess the molecular stability and flexibility profile of the porcine trypsin structures. 27012235 4 24 theme site-directed 540:552 arg1 mutations 554:562 glycosylation site-directed mutations 526:562 glycosylation site-directed mutations (A73S, N84S, and R104S) 526:586 Subsequently, glycosylation site-directed mutations (A73S, N84S, and R104S) were introduced within the Ω-loop region and its wing chain based on its potential N-glycosylation sites (Asn-Xaa-Ser/Thr consensus sequences) and structure information to improve the thermostability of trypsin. 27012235 4 24 theme site-directed 540:552 arg1 N84S 571:574 N84S 571:574 N84S 571:574 Subsequently, glycosylation site-directed mutations (A73S, N84S, and R104S) were introduced within the Ω-loop region and its wing chain based on its potential N-glycosylation sites (Asn-Xaa-Ser/Thr consensus sequences) and structure information to improve the thermostability of trypsin. 27012235 4 24 theme site-directed 540:552 arg1 R104S 581:585 R104S 581:585 R104S 581:585 Subsequently, glycosylation site-directed mutations (A73S, N84S, and R104S) were introduced within the Ω-loop region and its wing chain based on its potential N-glycosylation sites (Asn-Xaa-Ser/Thr consensus sequences) and structure information to improve the thermostability of trypsin. 27012235 4 24 theme site-directed 540:552 arg1 A73S 565:568 A73S 565:568 A73S 565:568 Subsequently, glycosylation site-directed mutations (A73S, N84S, and R104S) were introduced within the Ω-loop region and its wing chain based on its potential N-glycosylation sites (Asn-Xaa-Ser/Thr consensus sequences) and structure information to improve the thermostability of trypsin. 27012235 4 25 gly N-glycosylation 671:685 arg2 sites 687:691 its potential N-glycosylation sites 657:691 its potential N-glycosylation sites (Asn-Xaa-Ser/Thr consensus sequences) 657:729 Subsequently, glycosylation site-directed mutations (A73S, N84S, and R104S) were introduced within the Ω-loop region and its wing chain based on its potential N-glycosylation sites (Asn-Xaa-Ser/Thr consensus sequences) and structure information to improve the thermostability of trypsin. 27012235 4 25 gly N-glycosylation 671:685 arg2 sequences 720:728 Asn-Xaa-Ser/Thr consensus sequences 694:728 Asn-Xaa-Ser/Thr consensus sequences 694:728 Subsequently, glycosylation site-directed mutations (A73S, N84S, and R104S) were introduced within the Ω-loop region and its wing chain based on its potential N-glycosylation sites (Asn-Xaa-Ser/Thr consensus sequences) and structure information to improve the thermostability of trypsin. 27012235 2 26 theme dynamics 286:293 arg1 simulation 295:304 molecular dynamics simulation 276:304 molecular dynamics simulation 276:304 In the present study, molecular dynamics simulation was carried out to assess the molecular stability and flexibility profile of the porcine trypsin structures. 27012235 3 27 theme fragment 447:454 arg1 78-91 456:460 fragment 78-91 447:460 fragment 78-91 447:460 Two Ω-Loops (fragment 57-67 and fragment 78-91) were confirmed to represent the flexible region. 27012235 2 28 theme molecular 276:284 arg1 dynamics 286:293 molecular dynamics 276:293 molecular dynamics simulation 276:304 In the present study, molecular dynamics simulation was carried out to assess the molecular stability and flexibility profile of the porcine trypsin structures. 27012235 2 29 theme structures 403:412 arg1 profile 372:378 the molecular stability and flexibility profile 332:378 the molecular stability and flexibility profile of the porcine trypsin structures 332:412 In the present study, molecular dynamics simulation was carried out to assess the molecular stability and flexibility profile of the porcine trypsin structures. 27012235 8 30 dep information 1371:1381 arg1 modification 1410:1421 modification 1410:1421 modification 1410:1421 In conclusion, we obtained the thermostability-improved enzyme N84S mutant, and the strategy used to design this mutant based on its structural information and N-linked glycosylation modification could be applied to engineer other enzymes to meet the needs of the biotechnological industry. 27012235 1 31 theme molecular 193:201 arg1 recognition 203:213 molecular recognition 193:213 molecular recognition 193:213 The Ω-loop is a nonregular and flexible structure that plays an important role in molecular recognition, protein folding, and thermostability. 27012235 1 32 theme important 175:183 arg1 role 185:188 an important role 172:188 an important role 172:188 The Ω-loop is a nonregular and flexible structure that plays an important role in molecular recognition, protein folding, and thermostability. 27012235 2 33 theme trypsin 395:401 arg1 structures 403:412 the porcine trypsin structures 383:412 the porcine trypsin structures 383:412 In the present study, molecular dynamics simulation was carried out to assess the molecular stability and flexibility profile of the porcine trypsin structures. 27012235 0 34 theme Thermostability 21:35 arg1 Improvement 37:47 Thermostability Improvement 21:47 Thermostability Improvement of Trypsin 21:58 A Novel Strategy for Thermostability Improvement of Trypsin Based on N-Glycosylation within the Ω-Loop Region. 27012235 3 35 dep Ω-Loops 419:425 arg1 57-67 437:441 fragment 57-67 428:441 fragment 57-67 428:441 Two Ω-Loops (fragment 57-67 and fragment 78-91) were confirmed to represent the flexible region. 27012235 3 35 dep Ω-Loops 419:425 arg1 78-91 456:460 fragment 78-91 447:460 fragment 78-91 447:460 Two Ω-Loops (fragment 57-67 and fragment 78-91) were confirmed to represent the flexible region. 27012235 2 36 theme porcine 387:393 arg1 trypsin 395:401 porcine trypsin 387:401 the porcine trypsin structures 383:412 In the present study, molecular dynamics simulation was carried out to assess the molecular stability and flexibility profile of the porcine trypsin structures. 27012235 0 37 theme Trypsin 52:58 arg1 Improvement 37:47 Thermostability Improvement 21:47 Thermostability Improvement of Trypsin 21:58 A Novel Strategy for Thermostability Improvement of Trypsin Based on N-Glycosylation within the Ω-Loop Region. 27012235 7 38 theme wild-type 1156:1164 arg1 enzyme 1166:1171 the wild-type enzyme 1152:1171 the wild-type enzyme 1152:1171 Additionally, the optimum temperatures of the wild-type enzyme and the N84S mutant were 75°C and 80°C, respectively. 27012235 8 39 theme biotechnological 1491:1506 arg1 industry 1508:1515 the biotechnological industry 1487:1515 the biotechnological industry 1487:1515 In conclusion, we obtained the thermostability-improved enzyme N84S mutant, and the strategy used to design this mutant based on its structural information and N-linked glycosylation modification could be applied to engineer other enzymes to meet the needs of the biotechnological industry. 27012235 4 40 theme glycosylation 526:538 arg1 mutations 554:562 glycosylation site-directed mutations 526:562 glycosylation site-directed mutations (A73S, N84S, and R104S) 526:586 Subsequently, glycosylation site-directed mutations (A73S, N84S, and R104S) were introduced within the Ω-loop region and its wing chain based on its potential N-glycosylation sites (Asn-Xaa-Ser/Thr consensus sequences) and structure information to improve the thermostability of trypsin. 27012235 4 40 theme glycosylation 526:538 arg1 N84S 571:574 N84S 571:574 N84S 571:574 Subsequently, glycosylation site-directed mutations (A73S, N84S, and R104S) were introduced within the Ω-loop region and its wing chain based on its potential N-glycosylation sites (Asn-Xaa-Ser/Thr consensus sequences) and structure information to improve the thermostability of trypsin. 27012235 4 40 theme glycosylation 526:538 arg1 R104S 581:585 R104S 581:585 R104S 581:585 Subsequently, glycosylation site-directed mutations (A73S, N84S, and R104S) were introduced within the Ω-loop region and its wing chain based on its potential N-glycosylation sites (Asn-Xaa-Ser/Thr consensus sequences) and structure information to improve the thermostability of trypsin. 27012235 4 40 theme glycosylation 526:538 arg1 A73S 565:568 A73S 565:568 A73S 565:568 Subsequently, glycosylation site-directed mutations (A73S, N84S, and R104S) were introduced within the Ω-loop region and its wing chain based on its potential N-glycosylation sites (Asn-Xaa-Ser/Thr consensus sequences) and structure information to improve the thermostability of trypsin. 27012235 4 41 theme N-glycosylation 671:685 arg1 sites 687:691 its potential N-glycosylation sites 657:691 its potential N-glycosylation sites (Asn-Xaa-Ser/Thr consensus sequences) 657:729 Subsequently, glycosylation site-directed mutations (A73S, N84S, and R104S) were introduced within the Ω-loop region and its wing chain based on its potential N-glycosylation sites (Asn-Xaa-Ser/Thr consensus sequences) and structure information to improve the thermostability of trypsin. 27012235 4 41 theme N-glycosylation 671:685 arg1 sequences 720:728 Asn-Xaa-Ser/Thr consensus sequences 694:728 Asn-Xaa-Ser/Thr consensus sequences 694:728 Subsequently, glycosylation site-directed mutations (A73S, N84S, and R104S) were introduced within the Ω-loop region and its wing chain based on its potential N-glycosylation sites (Asn-Xaa-Ser/Thr consensus sequences) and structure information to improve the thermostability of trypsin. 27012235 1 42 theme nonregular 127:136 arg1 Ω-loop 115:120 The Ω-loop 111:120 The Ω-loop 111:120 The Ω-loop is a nonregular and flexible structure that plays an important role in molecular recognition, protein folding, and thermostability. 27012235 1 42 theme nonregular 127:136 arg1 structure 151:159 a nonregular and flexible structure 125:159 a nonregular and flexible structure that plays an important role in molecular recognition, protein folding, and thermostability 125:251 The Ω-loop is a nonregular and flexible structure that plays an important role in molecular recognition, protein folding, and thermostability. 27012235 8 43 theme structural 1360:1369 arg1 information 1371:1381 its structural information 1356:1381 its structural information 1356:1381 In conclusion, we obtained the thermostability-improved enzyme N84S mutant, and the strategy used to design this mutant based on its structural information and N-linked glycosylation modification could be applied to engineer other enzymes to meet the needs of the biotechnological industry. 27012235 4 44 theme Asn-Xaa-Ser/Thr 694:708 arg1 sites 687:691 its potential N-glycosylation sites 657:691 its potential N-glycosylation sites (Asn-Xaa-Ser/Thr consensus sequences) 657:729 Subsequently, glycosylation site-directed mutations (A73S, N84S, and R104S) were introduced within the Ω-loop region and its wing chain based on its potential N-glycosylation sites (Asn-Xaa-Ser/Thr consensus sequences) and structure information to improve the thermostability of trypsin. 27012235 4 44 theme Asn-Xaa-Ser/Thr 694:708 arg1 sequences 720:728 Asn-Xaa-Ser/Thr consensus sequences 694:728 Asn-Xaa-Ser/Thr consensus sequences 694:728 Subsequently, glycosylation site-directed mutations (A73S, N84S, and R104S) were introduced within the Ω-loop region and its wing chain based on its potential N-glycosylation sites (Asn-Xaa-Ser/Thr consensus sequences) and structure information to improve the thermostability of trypsin. 27012235 8 45 theme thermostability-improved 1258:1281 arg1 mutant 1295:1300 the thermostability-improved enzyme N84S mutant 1254:1300 the thermostability-improved enzyme N84S mutant 1254:1300 In conclusion, we obtained the thermostability-improved enzyme N84S mutant, and the strategy used to design this mutant based on its structural information and N-linked glycosylation modification could be applied to engineer other enzymes to meet the needs of the biotechnological industry. 27012235 6 46 from increase 1050:1057 arg1 values 1069:1074 the Tm values 1062:1074 the Tm values determined by circular dichroism 1062:1107 Furthermore, the significant increase in the thermal stability of the N84S mutant has also been proven by an increase in the Tm values determined by circular dichroism. 27012235 6 47 theme Tm 1066:1067 arg1 values 1069:1074 the Tm values 1062:1074 the Tm values determined by circular dichroism 1062:1107 Furthermore, the significant increase in the thermal stability of the N84S mutant has also been proven by an increase in the Tm values determined by circular dichroism. 27012235 1 48 theme protein 216:222 arg1 folding 224:230 protein folding 216:230 protein folding 216:230 The Ω-loop is a nonregular and flexible structure that plays an important role in molecular recognition, protein folding, and thermostability. 27012235 7 49 theme N84S 1181:1184 arg1 75°C 1198:1201 75°C 1198:1201 75°C 1198:1201 Additionally, the optimum temperatures of the wild-type enzyme and the N84S mutant were 75°C and 80°C, respectively. 27012235 7 49 theme N84S 1181:1184 arg1 mutant 1186:1191 the N84S mutant 1177:1191 the N84S mutant 1177:1191 Additionally, the optimum temperatures of the wild-type enzyme and the N84S mutant were 75°C and 80°C, respectively. 27012235 4 50 theme Ω-loop 615:620 arg1 region 622:627 the Ω-loop region 611:627 the Ω-loop region 611:627 Subsequently, glycosylation site-directed mutations (A73S, N84S, and R104S) were introduced within the Ω-loop region and its wing chain based on its potential N-glycosylation sites (Asn-Xaa-Ser/Thr consensus sequences) and structure information to improve the thermostability of trypsin. 27012235 4 51 theme trypsin 791:797 arg1 thermostability 772:786 the thermostability 768:786 the thermostability of trypsin 768:797 Subsequently, glycosylation site-directed mutations (A73S, N84S, and R104S) were introduced within the Ω-loop region and its wing chain based on its potential N-glycosylation sites (Asn-Xaa-Ser/Thr consensus sequences) and structure information to improve the thermostability of trypsin. 27012235 3 52 theme flexible 495:502 arg1 region 504:509 the flexible region 491:509 the flexible region 491:509 Two Ω-Loops (fragment 57-67 and fragment 78-91) were confirmed to represent the flexible region. 27012235 5 53 theme N84S 849:852 arg1 mutant 854:859 the N84S mutant 845:859 the N84S mutant 845:859 The result demonstrated that the halflife of the N84S mutant at 50°C increased by 177.89 min when compared with that of the wildtype enzyme. 27012235 6 54 theme thermal 986:992 arg1 stability 994:1002 the thermal stability 982:1002 the thermal stability of the N84S mutant 982:1021 Furthermore, the significant increase in the thermal stability of the N84S mutant has also been proven by an increase in the Tm values determined by circular dichroism. 27012235 4 55 theme wing 637:640 arg1 chain 642:646 its wing chain 633:646 its wing chain 633:646 Subsequently, glycosylation site-directed mutations (A73S, N84S, and R104S) were introduced within the Ω-loop region and its wing chain based on its potential N-glycosylation sites (Asn-Xaa-Ser/Thr consensus sequences) and structure information to improve the thermostability of trypsin. 27012235 6 56 theme circular 1090:1097 arg1 dichroism 1099:1107 circular dichroism 1090:1107 circular dichroism 1090:1107 Furthermore, the significant increase in the thermal stability of the N84S mutant has also been proven by an increase in the Tm values determined by circular dichroism. 27012235 8 57 dep the 1474:1476 arg1 needs 1478:1482 needs 1478:1482 needs 1478:1482 In conclusion, we obtained the thermostability-improved enzyme N84S mutant, and the strategy used to design this mutant based on its structural information and N-linked glycosylation modification could be applied to engineer other enzymes to meet the needs of the biotechnological industry. 27012235 2 58 theme stability 346:354 arg1 profile 372:378 the molecular stability and flexibility profile 332:378 the molecular stability and flexibility profile of the porcine trypsin structures 332:412 In the present study, molecular dynamics simulation was carried out to assess the molecular stability and flexibility profile of the porcine trypsin structures. 27012235 6 59 theme N84S 1011:1014 arg1 mutant 1016:1021 the N84S mutant 1007:1021 the N84S mutant 1007:1021 Furthermore, the significant increase in the thermal stability of the N84S mutant has also been proven by an increase in the Tm values determined by circular dichroism. 26847925 0 0 theme ER 77:78 arg1 control 101:107 ER glycoprotein quality control 77:107 ER glycoprotein quality control 77:107 Structural basis for two-step glucose trimming by glucosidase II involved in ER glycoprotein quality control. 26847925 1 1 theme proteins 239:246 arg1 folding 210:216 the efficient folding 196:216 the efficient folding of newly synthesized proteins 196:246 The endoplasmic reticulum (ER) has a sophisticated protein quality control system for the efficient folding of newly synthesized proteins. 26847925 5 2 theme substrates 954:963 arg1 kinds 945:949 the two kinds 937:949 the two kinds of substrates 937:963 Our structural data revealed that the nonreducing terminal disaccharide moieties of the two kinds of substrates can be accommodated in a gourd-shaped bilocular pocket, thereby providing a structural basis for substrate-binding specificity in the two-step deglucosylation catalyzed by this enzyme. 26847925 3 3 theme quality 538:544 arg1 tag 562:564 a quality control protein tag 536:564 a quality control protein tag that is transiently expressed on glycoproteins and recognized by ER chaperones 536:643 Glucosidase II catalyzes two-step hydrolysis at α1,3-linked glucose-glucose and glucose-mannose residues of high-mannose-type glycans to generate a quality control protein tag that is transiently expressed on glycoproteins and recognized by ER chaperones. 26847925 0 4 theme quality 93:99 arg1 control 101:107 ER glycoprotein quality control 77:107 ER glycoprotein quality control 77:107 Structural basis for two-step glucose trimming by glucosidase II involved in ER glycoprotein quality control. 26847925 5 5 theme bilocular 1003:1011 arg1 pocket 1013:1018 a gourd-shaped bilocular pocket 988:1018 a gourd-shaped bilocular pocket 988:1018 Our structural data revealed that the nonreducing terminal disaccharide moieties of the two kinds of substrates can be accommodated in a gourd-shaped bilocular pocket, thereby providing a structural basis for substrate-binding specificity in the two-step deglucosylation catalyzed by this enzyme. 26847925 4 6 theme catalytic 695:703 arg1 GIIα 734:737 GIIα 734:737 GIIα 734:737 Here we determined the crystal structures of the catalytic α subunit of glucosidase II (GIIα) complexed with two different glucosyl ligands containing the scissile bonds of first- and second-step reactions. 26847925 4 6 theme catalytic 695:703 arg1 subunit 707:713 the catalytic α subunit 691:713 the catalytic α subunit of glucosidase II (GIIα) complexed with two different glucosyl ligands containing the scissile bonds of first- and second-step reactions 691:850 Here we determined the crystal structures of the catalytic α subunit of glucosidase II (GIIα) complexed with two different glucosyl ligands containing the scissile bonds of first- and second-step reactions. 26847925 0 7 theme glycoprotein 80:91 arg1 control 101:107 ER glycoprotein quality control 77:107 ER glycoprotein quality control 77:107 Structural basis for two-step glucose trimming by glucosidase II involved in ER glycoprotein quality control. 26847925 5 8 theme nonreducing 891:901 arg1 moieties 925:932 the nonreducing terminal disaccharide moieties 887:932 the nonreducing terminal disaccharide moieties of the two kinds of substrates 887:963 Our structural data revealed that the nonreducing terminal disaccharide moieties of the two kinds of substrates can be accommodated in a gourd-shaped bilocular pocket, thereby providing a structural basis for substrate-binding specificity in the two-step deglucosylation catalyzed by this enzyme. 26847925 1 9 contain has 141:143 arg1 reticulum 126:134 The endoplasmic reticulum 110:134 The endoplasmic reticulum (ER) 110:139 The endoplasmic reticulum (ER) has a sophisticated protein quality control system for the efficient folding of newly synthesized proteins. 26847925 1 9 contain has 141:143 arg2 system 185:190 a sophisticated protein quality control system 145:190 a sophisticated protein quality control system for the efficient folding of newly synthesized proteins 145:246 The endoplasmic reticulum (ER) has a sophisticated protein quality control system for the efficient folding of newly synthesized proteins. 26847925 1 9 contain has 141:143 arg1 ER 137:138 ER 137:138 ER 137:138 The endoplasmic reticulum (ER) has a sophisticated protein quality control system for the efficient folding of newly synthesized proteins. 26847925 4 10 theme different 759:767 arg1 ligands 778:784 two different glucosyl ligands 755:784 two different glucosyl ligands containing the scissile bonds of first- and second-step reactions 755:850 Here we determined the crystal structures of the catalytic α subunit of glucosidase II (GIIα) complexed with two different glucosyl ligands containing the scissile bonds of first- and second-step reactions. 26847925 2 11 theme intracellular 367:379 arg1 lectins 381:387 intracellular lectins 367:387 intracellular lectins 367:387 In this system, a variety of N-linked oligosaccharides displayed on proteins serve as signals recognized by series of intracellular lectins. 26847925 1 12 theme sophisticated 147:159 arg1 system 185:190 a sophisticated protein quality control system 145:190 a sophisticated protein quality control system for the efficient folding of newly synthesized proteins 145:246 The endoplasmic reticulum (ER) has a sophisticated protein quality control system for the efficient folding of newly synthesized proteins. 26847925 5 13 theme kinds 945:949 arg1 moieties 925:932 the nonreducing terminal disaccharide moieties 887:932 the nonreducing terminal disaccharide moieties of the two kinds of substrates 887:963 Our structural data revealed that the nonreducing terminal disaccharide moieties of the two kinds of substrates can be accommodated in a gourd-shaped bilocular pocket, thereby providing a structural basis for substrate-binding specificity in the two-step deglucosylation catalyzed by this enzyme. 26847925 4 14 theme scissile 801:808 arg1 bonds 810:814 the scissile bonds 797:814 the scissile bonds of first- and second-step reactions 797:850 Here we determined the crystal structures of the catalytic α subunit of glucosidase II (GIIα) complexed with two different glucosyl ligands containing the scissile bonds of first- and second-step reactions. 26847925 1 15 theme protein 161:167 arg1 system 185:190 a sophisticated protein quality control system 145:190 a sophisticated protein quality control system for the efficient folding of newly synthesized proteins 145:246 The endoplasmic reticulum (ER) has a sophisticated protein quality control system for the efficient folding of newly synthesized proteins. 26847925 3 16 link α1,3-linked 438:448 arg1 residues 486:493 α1,3-linked glucose-glucose and glucose-mannose residues 438:493 α1,3-linked glucose-glucose and glucose-mannose residues of high-mannose-type glycans 438:522 Glucosidase II catalyzes two-step hydrolysis at α1,3-linked glucose-glucose and glucose-mannose residues of high-mannose-type glycans to generate a quality control protein tag that is transiently expressed on glycoproteins and recognized by ER chaperones. 26847925 3 16 link α1,3-linked 438:448 arg1 glycans 516:522 high-mannose-type glycans 498:522 high-mannose-type glycans 498:522 Glucosidase II catalyzes two-step hydrolysis at α1,3-linked glucose-glucose and glucose-mannose residues of high-mannose-type glycans to generate a quality control protein tag that is transiently expressed on glycoproteins and recognized by ER chaperones. 26847925 0 17 gly glycoprotein 80:91 arg1 glycoprotein 80:91 ER glycoprotein quality control 77:107 ER glycoprotein quality control 77:107 Structural basis for two-step glucose trimming by glucosidase II involved in ER glycoprotein quality control. 26847925 1 18 theme quality 169:175 arg1 system 185:190 a sophisticated protein quality control system 145:190 a sophisticated protein quality control system for the efficient folding of newly synthesized proteins 145:246 The endoplasmic reticulum (ER) has a sophisticated protein quality control system for the efficient folding of newly synthesized proteins. 26847925 0 19 theme Structural 0:9 arg1 basis 11:15 Structural basis 0:15 Structural basis for two-step glucose trimming by glucosidase II 0:63 Structural basis for two-step glucose trimming by glucosidase II involved in ER glycoprotein quality control. 26847925 2 20 theme oligosaccharides 287:302 arg1 variety 267:273 a variety 265:273 a variety of N-linked oligosaccharides displayed on proteins 265:324 In this system, a variety of N-linked oligosaccharides displayed on proteins serve as signals recognized by series of intracellular lectins. 26847925 2 20 theme oligosaccharides 287:302 arg1 oligosaccharides 287:302 N-linked oligosaccharides 278:302 N-linked oligosaccharides displayed on proteins 278:324 In this system, a variety of N-linked oligosaccharides displayed on proteins serve as signals recognized by series of intracellular lectins. 26847925 2 20 theme oligosaccharides 287:302 arg1 signals 335:341 signals 335:341 signals recognized by series of intracellular lectins 335:387 In this system, a variety of N-linked oligosaccharides displayed on proteins serve as signals recognized by series of intracellular lectins. 26847925 1 21 theme control 177:183 arg1 system 185:190 a sophisticated protein quality control system 145:190 a sophisticated protein quality control system for the efficient folding of newly synthesized proteins 145:246 The endoplasmic reticulum (ER) has a sophisticated protein quality control system for the efficient folding of newly synthesized proteins. 26847925 0 22 theme two-step 21:28 arg1 trimming 38:45 two-step glucose trimming 21:45 two-step glucose trimming 21:45 Structural basis for two-step glucose trimming by glucosidase II involved in ER glycoprotein quality control. 26847925 5 23 theme structural 1041:1050 arg1 basis 1052:1056 a structural basis 1039:1056 a structural basis for substrate-binding specificity 1039:1090 Our structural data revealed that the nonreducing terminal disaccharide moieties of the two kinds of substrates can be accommodated in a gourd-shaped bilocular pocket, thereby providing a structural basis for substrate-binding specificity in the two-step deglucosylation catalyzed by this enzyme. 26847925 2 24 theme N-linked 278:285 arg1 oligosaccharides 287:302 N-linked oligosaccharides 278:302 N-linked oligosaccharides displayed on proteins 278:324 In this system, a variety of N-linked oligosaccharides displayed on proteins serve as signals recognized by series of intracellular lectins. 26847925 5 25 theme gourd-shaped 990:1001 arg1 pocket 1013:1018 a gourd-shaped bilocular pocket 988:1018 a gourd-shaped bilocular pocket 988:1018 Our structural data revealed that the nonreducing terminal disaccharide moieties of the two kinds of substrates can be accommodated in a gourd-shaped bilocular pocket, thereby providing a structural basis for substrate-binding specificity in the two-step deglucosylation catalyzed by this enzyme. 26847925 4 26 theme crystal 669:675 arg1 structures 677:686 the crystal structures 665:686 the crystal structures of the catalytic α subunit of glucosidase II (GIIα) complexed with two different glucosyl ligands containing the scissile bonds of first- and second-step reactions 665:850 Here we determined the crystal structures of the catalytic α subunit of glucosidase II (GIIα) complexed with two different glucosyl ligands containing the scissile bonds of first- and second-step reactions. 26847925 5 27 theme structural 857:866 arg1 data 868:871 Our structural data 853:871 Our structural data 853:871 Our structural data revealed that the nonreducing terminal disaccharide moieties of the two kinds of substrates can be accommodated in a gourd-shaped bilocular pocket, thereby providing a structural basis for substrate-binding specificity in the two-step deglucosylation catalyzed by this enzyme. 26847925 4 28 theme glucosyl 769:776 arg1 ligands 778:784 two different glucosyl ligands 755:784 two different glucosyl ligands containing the scissile bonds of first- and second-step reactions 755:850 Here we determined the crystal structures of the catalytic α subunit of glucosidase II (GIIα) complexed with two different glucosyl ligands containing the scissile bonds of first- and second-step reactions. 26847925 4 29 theme glucosidase 718:728 arg1 GIIα 734:737 GIIα 734:737 GIIα 734:737 Here we determined the crystal structures of the catalytic α subunit of glucosidase II (GIIα) complexed with two different glucosyl ligands containing the scissile bonds of first- and second-step reactions. 26847925 4 29 theme glucosidase 718:728 arg1 subunit 707:713 the catalytic α subunit 691:713 the catalytic α subunit of glucosidase II (GIIα) complexed with two different glucosyl ligands containing the scissile bonds of first- and second-step reactions 691:850 Here we determined the crystal structures of the catalytic α subunit of glucosidase II (GIIα) complexed with two different glucosyl ligands containing the scissile bonds of first- and second-step reactions. 26847925 3 30 gly glycoproteins 599:611 arg1 glycoproteins 599:611 glycoproteins 599:611 glycoproteins 599:611 Glucosidase II catalyzes two-step hydrolysis at α1,3-linked glucose-glucose and glucose-mannose residues of high-mannose-type glycans to generate a quality control protein tag that is transiently expressed on glycoproteins and recognized by ER chaperones. 26847925 3 31 theme ER 631:632 arg1 chaperones 634:643 ER chaperones 631:643 ER chaperones 631:643 Glucosidase II catalyzes two-step hydrolysis at α1,3-linked glucose-glucose and glucose-mannose residues of high-mannose-type glycans to generate a quality control protein tag that is transiently expressed on glycoproteins and recognized by ER chaperones. 26847925 4 32 theme α 705:705 arg1 GIIα 734:737 GIIα 734:737 GIIα 734:737 Here we determined the crystal structures of the catalytic α subunit of glucosidase II (GIIα) complexed with two different glucosyl ligands containing the scissile bonds of first- and second-step reactions. 26847925 4 32 theme α 705:705 arg1 subunit 707:713 the catalytic α subunit 691:713 the catalytic α subunit of glucosidase II (GIIα) complexed with two different glucosyl ligands containing the scissile bonds of first- and second-step reactions 691:850 Here we determined the crystal structures of the catalytic α subunit of glucosidase II (GIIα) complexed with two different glucosyl ligands containing the scissile bonds of first- and second-step reactions. 26847925 5 33 theme disaccharide 912:923 arg1 moieties 925:932 the nonreducing terminal disaccharide moieties 887:932 the nonreducing terminal disaccharide moieties of the two kinds of substrates 887:963 Our structural data revealed that the nonreducing terminal disaccharide moieties of the two kinds of substrates can be accommodated in a gourd-shaped bilocular pocket, thereby providing a structural basis for substrate-binding specificity in the two-step deglucosylation catalyzed by this enzyme. 26847925 0 34 theme glucose 30:36 arg1 trimming 38:45 two-step glucose trimming 21:45 two-step glucose trimming 21:45 Structural basis for two-step glucose trimming by glucosidase II involved in ER glycoprotein quality control. 26847925 2 35 link N-linked 278:285 arg1 oligosaccharides 287:302 N-linked oligosaccharides 278:302 N-linked oligosaccharides displayed on proteins 278:324 In this system, a variety of N-linked oligosaccharides displayed on proteins serve as signals recognized by series of intracellular lectins. 26847925 3 36 theme two-step 415:422 arg1 hydrolysis 424:433 two-step hydrolysis 415:433 two-step hydrolysis at α1,3-linked glucose-glucose and glucose-mannose residues of high-mannose-type glycans 415:522 Glucosidase II catalyzes two-step hydrolysis at α1,3-linked glucose-glucose and glucose-mannose residues of high-mannose-type glycans to generate a quality control protein tag that is transiently expressed on glycoproteins and recognized by ER chaperones. 26847925 4 37 theme reactions 842:850 arg1 bonds 810:814 the scissile bonds 797:814 the scissile bonds of first- and second-step reactions 797:850 Here we determined the crystal structures of the catalytic α subunit of glucosidase II (GIIα) complexed with two different glucosyl ligands containing the scissile bonds of first- and second-step reactions. 26847925 1 38 theme efficient 200:208 arg1 folding 210:216 the efficient folding 196:216 the efficient folding of newly synthesized proteins 196:246 The endoplasmic reticulum (ER) has a sophisticated protein quality control system for the efficient folding of newly synthesized proteins. 26847925 4 39 theme subunit 707:713 arg1 structures 677:686 the crystal structures 665:686 the crystal structures of the catalytic α subunit of glucosidase II (GIIα) complexed with two different glucosyl ligands containing the scissile bonds of first- and second-step reactions 665:850 Here we determined the crystal structures of the catalytic α subunit of glucosidase II (GIIα) complexed with two different glucosyl ligands containing the scissile bonds of first- and second-step reactions. 26847925 3 40 theme α1,3-linked 438:448 arg1 residues 486:493 α1,3-linked glucose-glucose and glucose-mannose residues 438:493 α1,3-linked glucose-glucose and glucose-mannose residues of high-mannose-type glycans 438:522 Glucosidase II catalyzes two-step hydrolysis at α1,3-linked glucose-glucose and glucose-mannose residues of high-mannose-type glycans to generate a quality control protein tag that is transiently expressed on glycoproteins and recognized by ER chaperones. 26847925 3 40 theme α1,3-linked 438:448 arg1 glycans 516:522 high-mannose-type glycans 498:522 high-mannose-type glycans 498:522 Glucosidase II catalyzes two-step hydrolysis at α1,3-linked glucose-glucose and glucose-mannose residues of high-mannose-type glycans to generate a quality control protein tag that is transiently expressed on glycoproteins and recognized by ER chaperones. 26847925 4 41 contain containing 786:795 arg2 bonds 810:814 the scissile bonds 797:814 the scissile bonds of first- and second-step reactions 797:850 Here we determined the crystal structures of the catalytic α subunit of glucosidase II (GIIα) complexed with two different glucosyl ligands containing the scissile bonds of first- and second-step reactions. 26847925 4 41 contain containing 786:795 arg1 ligands 778:784 two different glucosyl ligands 755:784 two different glucosyl ligands containing the scissile bonds of first- and second-step reactions 755:850 Here we determined the crystal structures of the catalytic α subunit of glucosidase II (GIIα) complexed with two different glucosyl ligands containing the scissile bonds of first- and second-step reactions. 26847925 3 42 from residues 486:493 arg1 hydrolysis 424:433 two-step hydrolysis 415:433 two-step hydrolysis at α1,3-linked glucose-glucose and glucose-mannose residues of high-mannose-type glycans 415:522 Glucosidase II catalyzes two-step hydrolysis at α1,3-linked glucose-glucose and glucose-mannose residues of high-mannose-type glycans to generate a quality control protein tag that is transiently expressed on glycoproteins and recognized by ER chaperones. 26847925 1 43 theme endoplasmic 114:124 arg1 reticulum 126:134 The endoplasmic reticulum 110:134 The endoplasmic reticulum (ER) 110:139 The endoplasmic reticulum (ER) has a sophisticated protein quality control system for the efficient folding of newly synthesized proteins. 26847925 1 43 theme endoplasmic 114:124 arg1 ER 137:138 ER 137:138 ER 137:138 The endoplasmic reticulum (ER) has a sophisticated protein quality control system for the efficient folding of newly synthesized proteins. 26847925 5 44 theme two-step 1099:1106 arg1 deglucosylation 1108:1122 the two-step deglucosylation 1095:1122 the two-step deglucosylation catalyzed by this enzyme 1095:1147 Our structural data revealed that the nonreducing terminal disaccharide moieties of the two kinds of substrates can be accommodated in a gourd-shaped bilocular pocket, thereby providing a structural basis for substrate-binding specificity in the two-step deglucosylation catalyzed by this enzyme. 26847925 4 45 theme first- 819:824 arg1 reactions 842:850 first- and second-step reactions 819:850 first- and second-step reactions 819:850 Here we determined the crystal structures of the catalytic α subunit of glucosidase II (GIIα) complexed with two different glucosyl ligands containing the scissile bonds of first- and second-step reactions. 26847925 5 46 theme substrate-binding 1062:1078 arg1 specificity 1080:1090 substrate-binding specificity 1062:1090 substrate-binding specificity 1062:1090 Our structural data revealed that the nonreducing terminal disaccharide moieties of the two kinds of substrates can be accommodated in a gourd-shaped bilocular pocket, thereby providing a structural basis for substrate-binding specificity in the two-step deglucosylation catalyzed by this enzyme. 26847925 3 47 theme high-mannose-type 498:514 arg1 glycans 516:522 high-mannose-type glycans 498:522 high-mannose-type glycans 498:522 Glucosidase II catalyzes two-step hydrolysis at α1,3-linked glucose-glucose and glucose-mannose residues of high-mannose-type glycans to generate a quality control protein tag that is transiently expressed on glycoproteins and recognized by ER chaperones. 26847925 3 48 theme glycans 516:522 arg1 residues 486:493 α1,3-linked glucose-glucose and glucose-mannose residues 438:493 α1,3-linked glucose-glucose and glucose-mannose residues of high-mannose-type glycans 438:522 Glucosidase II catalyzes two-step hydrolysis at α1,3-linked glucose-glucose and glucose-mannose residues of high-mannose-type glycans to generate a quality control protein tag that is transiently expressed on glycoproteins and recognized by ER chaperones. 26847925 3 48 theme glycans 516:522 arg1 glycans 516:522 high-mannose-type glycans 498:522 high-mannose-type glycans 498:522 Glucosidase II catalyzes two-step hydrolysis at α1,3-linked glucose-glucose and glucose-mannose residues of high-mannose-type glycans to generate a quality control protein tag that is transiently expressed on glycoproteins and recognized by ER chaperones. 26847925 3 49 theme glucose-glucose 450:464 arg1 residues 486:493 α1,3-linked glucose-glucose and glucose-mannose residues 438:493 α1,3-linked glucose-glucose and glucose-mannose residues of high-mannose-type glycans 438:522 Glucosidase II catalyzes two-step hydrolysis at α1,3-linked glucose-glucose and glucose-mannose residues of high-mannose-type glycans to generate a quality control protein tag that is transiently expressed on glycoproteins and recognized by ER chaperones. 26847925 3 49 theme glucose-glucose 450:464 arg1 glycans 516:522 high-mannose-type glycans 498:522 high-mannose-type glycans 498:522 Glucosidase II catalyzes two-step hydrolysis at α1,3-linked glucose-glucose and glucose-mannose residues of high-mannose-type glycans to generate a quality control protein tag that is transiently expressed on glycoproteins and recognized by ER chaperones. 26847925 3 50 theme glucose-mannose 470:484 arg1 residues 486:493 α1,3-linked glucose-glucose and glucose-mannose residues 438:493 α1,3-linked glucose-glucose and glucose-mannose residues of high-mannose-type glycans 438:522 Glucosidase II catalyzes two-step hydrolysis at α1,3-linked glucose-glucose and glucose-mannose residues of high-mannose-type glycans to generate a quality control protein tag that is transiently expressed on glycoproteins and recognized by ER chaperones. 26847925 3 50 theme glucose-mannose 470:484 arg1 glycans 516:522 high-mannose-type glycans 498:522 high-mannose-type glycans 498:522 Glucosidase II catalyzes two-step hydrolysis at α1,3-linked glucose-glucose and glucose-mannose residues of high-mannose-type glycans to generate a quality control protein tag that is transiently expressed on glycoproteins and recognized by ER chaperones. 26847925 4 51 theme second-step 830:840 arg1 reactions 842:850 first- and second-step reactions 819:850 first- and second-step reactions 819:850 Here we determined the crystal structures of the catalytic α subunit of glucosidase II (GIIα) complexed with two different glucosyl ligands containing the scissile bonds of first- and second-step reactions. 26847925 3 52 theme control 546:552 arg1 tag 562:564 a quality control protein tag 536:564 a quality control protein tag that is transiently expressed on glycoproteins and recognized by ER chaperones 536:643 Glucosidase II catalyzes two-step hydrolysis at α1,3-linked glucose-glucose and glucose-mannose residues of high-mannose-type glycans to generate a quality control protein tag that is transiently expressed on glycoproteins and recognized by ER chaperones. 26847925 2 53 theme lectins 381:387 arg1 series 357:362 series 357:362 series of intracellular lectins 357:387 In this system, a variety of N-linked oligosaccharides displayed on proteins serve as signals recognized by series of intracellular lectins. 26847925 5 54 theme terminal 903:910 arg1 moieties 925:932 the nonreducing terminal disaccharide moieties 887:932 the nonreducing terminal disaccharide moieties of the two kinds of substrates 887:963 Our structural data revealed that the nonreducing terminal disaccharide moieties of the two kinds of substrates can be accommodated in a gourd-shaped bilocular pocket, thereby providing a structural basis for substrate-binding specificity in the two-step deglucosylation catalyzed by this enzyme. 26847925 3 55 theme protein 554:560 arg1 tag 562:564 a quality control protein tag 536:564 a quality control protein tag that is transiently expressed on glycoproteins and recognized by ER chaperones 536:643 Glucosidase II catalyzes two-step hydrolysis at α1,3-linked glucose-glucose and glucose-mannose residues of high-mannose-type glycans to generate a quality control protein tag that is transiently expressed on glycoproteins and recognized by ER chaperones. 26847925 1 56 theme synthesized 227:237 arg1 proteins 239:246 newly synthesized proteins 221:246 newly synthesized proteins 221:246 The endoplasmic reticulum (ER) has a sophisticated protein quality control system for the efficient folding of newly synthesized proteins. 26257013 6 0 gly N-glycosites 1119:1130 arg2 N-glycosites 1119:1130 N-glycosites 1119:1130 N-glycosites 1119:1130 It was found that this new method led to significant increase in the identification of N-glycosites compared with the conventional hydrazide chemistry method. 26257013 5 1 theme proteome 1014:1021 arg1 samples 1023:1029 proteome samples 1014:1029 glycoprotein standards as well as proteome samples 980:1029 This new method was validated by analysis of glycoprotein standards as well as proteome samples. 26257013 0 2 theme Glycoproteomics 78:92 arg1 Analysis 94:101 Glycoproteomics Analysis 78:101 Glycoproteomics Analysis 78:101 Amine Chemistry Method for Selective Enrichment of N-Linked Glycopeptides for Glycoproteomics Analysis. 26257013 3 3 theme cyanoborohydride 708:723 arg1 presence 689:696 the presence 685:696 the presence of sodium cyanoborohydride 685:723 The first one was to block the primary amines in the peptides by addition of formaldehyde and sodium cyanoborohydride into the peptide sample, and the second one was to couple the glycopeptides onto solid phase beads by incubating the glycopeptides containing aldehyde groups (oxidized by periodate) with the amine-functionalized beads in the presence of sodium cyanoborohydride. 26257013 4 4 theme chemistry 888:896 arg1 method 898:903 the amine chemistry method 878:903 the amine chemistry method 878:903 It was demonstrated that the blocking of primary amines in the peptides by the first reductive amination reaction prior to the periodate oxidation made the amine chemistry method very efficient and sensitive. 26257013 6 5 from increase 1085:1092 arg1 identification 1101:1114 the identification 1097:1114 the identification of N-glycosites 1097:1130 It was found that this new method led to significant increase in the identification of N-glycosites compared with the conventional hydrazide chemistry method. 26257013 1 6 theme N-glycopeptides 166:180 arg1 extraction 152:161 the extraction 148:161 the extraction of N-glycopeptides using amine-functionalized beads for glycoproteomics analysis 148:242 An amine chemistry method was developed for the extraction of N-glycopeptides using amine-functionalized beads for glycoproteomics analysis. 26257013 5 7 theme samples 1023:1029 arg1 analysis 968:975 analysis 968:975 analysis of glycoprotein standards as well as proteome samples 968:1029 This new method was validated by analysis of glycoprotein standards as well as proteome samples. 26257013 2 8 theme amination 259:267 arg1 reactions 269:277 Two reductive amination reactions 245:277 Two reductive amination reactions between primary amine and aldehyde 245:312 Two reductive amination reactions between primary amine and aldehyde were employed in this approach. 26257013 5 9 theme standards 993:1001 arg1 analysis 968:975 analysis 968:975 analysis of glycoprotein standards as well as proteome samples 968:1029 This new method was validated by analysis of glycoprotein standards as well as proteome samples. 26257013 4 10 theme amines 775:780 arg1 blocking 755:762 the blocking 751:762 the blocking of primary amines in the peptides by the first reductive amination reaction prior to the periodate oxidation 751:871 It was demonstrated that the blocking of primary amines in the peptides by the first reductive amination reaction prior to the periodate oxidation made the amine chemistry method very efficient and sensitive. 26257013 3 11 gly glycopeptides 526:538 arg2 glycopeptides 526:538 the glycopeptides 522:538 the glycopeptides onto solid phase beads 522:561 The first one was to block the primary amines in the peptides by addition of formaldehyde and sodium cyanoborohydride into the peptide sample, and the second one was to couple the glycopeptides onto solid phase beads by incubating the glycopeptides containing aldehyde groups (oxidized by periodate) with the amine-functionalized beads in the presence of sodium cyanoborohydride. 26257013 3 12 from beads 676:680 arg1 presence 689:696 the presence 685:696 the presence of sodium cyanoborohydride 685:723 The first one was to block the primary amines in the peptides by addition of formaldehyde and sodium cyanoborohydride into the peptide sample, and the second one was to couple the glycopeptides onto solid phase beads by incubating the glycopeptides containing aldehyde groups (oxidized by periodate) with the amine-functionalized beads in the presence of sodium cyanoborohydride. 26257013 6 13 theme hydrazide 1163:1171 arg1 method 1183:1188 the conventional hydrazide chemistry method 1146:1188 the conventional hydrazide chemistry method 1146:1188 It was found that this new method led to significant increase in the identification of N-glycosites compared with the conventional hydrazide chemistry method. 26257013 3 14 theme solid 545:549 arg1 beads 557:561 solid phase beads 545:561 solid phase beads 545:561 The first one was to block the primary amines in the peptides by addition of formaldehyde and sodium cyanoborohydride into the peptide sample, and the second one was to couple the glycopeptides onto solid phase beads by incubating the glycopeptides containing aldehyde groups (oxidized by periodate) with the amine-functionalized beads in the presence of sodium cyanoborohydride. 26257013 3 15 theme primary 377:383 arg1 amines 385:390 the primary amines 373:390 the primary amines in the peptides 373:406 The first one was to block the primary amines in the peptides by addition of formaldehyde and sodium cyanoborohydride into the peptide sample, and the second one was to couple the glycopeptides onto solid phase beads by incubating the glycopeptides containing aldehyde groups (oxidized by periodate) with the amine-functionalized beads in the presence of sodium cyanoborohydride. 26257013 3 16 theme phase 551:555 arg1 beads 557:561 solid phase beads 545:561 solid phase beads 545:561 The first one was to block the primary amines in the peptides by addition of formaldehyde and sodium cyanoborohydride into the peptide sample, and the second one was to couple the glycopeptides onto solid phase beads by incubating the glycopeptides containing aldehyde groups (oxidized by periodate) with the amine-functionalized beads in the presence of sodium cyanoborohydride. 26257013 1 17 theme amine-functionalized 188:207 arg1 beads 209:213 amine-functionalized beads 188:213 amine-functionalized beads 188:213 An amine chemistry method was developed for the extraction of N-glycopeptides using amine-functionalized beads for glycoproteomics analysis. 26257013 0 18 theme Chemistry 6:14 arg1 Method 16:21 Amine Chemistry Method 0:21 Amine Chemistry Method for Selective Enrichment of N-Linked Glycopeptides for Glycoproteomics Analysis. 0:102 Amine Chemistry Method for Selective Enrichment of N-Linked Glycopeptides for Glycoproteomics Analysis. 26257013 4 19 theme amine 882:886 arg1 method 898:903 the amine chemistry method 878:903 the amine chemistry method 878:903 It was demonstrated that the blocking of primary amines in the peptides by the first reductive amination reaction prior to the periodate oxidation made the amine chemistry method very efficient and sensitive. 26257013 4 20 theme primary 767:773 arg1 amines 775:780 primary amines 767:780 primary amines 767:780 It was demonstrated that the blocking of primary amines in the peptides by the first reductive amination reaction prior to the periodate oxidation made the amine chemistry method very efficient and sensitive. 26257013 3 21 theme cyanoborohydride 447:462 arg1 addition 411:418 addition 411:418 addition of formaldehyde and sodium cyanoborohydride 411:462 The first one was to block the primary amines in the peptides by addition of formaldehyde and sodium cyanoborohydride into the peptide sample, and the second one was to couple the glycopeptides onto solid phase beads by incubating the glycopeptides containing aldehyde groups (oxidized by periodate) with the amine-functionalized beads in the presence of sodium cyanoborohydride. 26257013 0 22 theme Amine 0:4 arg1 Method 16:21 Amine Chemistry Method 0:21 Amine Chemistry Method for Selective Enrichment of N-Linked Glycopeptides for Glycoproteomics Analysis. 0:102 Amine Chemistry Method for Selective Enrichment of N-Linked Glycopeptides for Glycoproteomics Analysis. 26257013 6 23 theme significant 1073:1083 arg1 increase 1085:1092 significant increase 1073:1092 significant increase in the identification of N-glycosites 1073:1130 It was found that this new method led to significant increase in the identification of N-glycosites compared with the conventional hydrazide chemistry method. 26257013 1 24 theme amine 107:111 arg1 method 123:128 An amine chemistry method 104:128 An amine chemistry method 104:128 An amine chemistry method was developed for the extraction of N-glycopeptides using amine-functionalized beads for glycoproteomics analysis. 26257013 1 25 theme glycoproteomics 219:233 arg1 analysis 235:242 glycoproteomics analysis 219:242 glycoproteomics analysis 219:242 An amine chemistry method was developed for the extraction of N-glycopeptides using amine-functionalized beads for glycoproteomics analysis. 26257013 3 26 contain containing 595:604 arg1 glycopeptides 581:593 the glycopeptides 577:593 the glycopeptides containing aldehyde groups (oxidized by periodate) 577:644 The first one was to block the primary amines in the peptides by addition of formaldehyde and sodium cyanoborohydride into the peptide sample, and the second one was to couple the glycopeptides onto solid phase beads by incubating the glycopeptides containing aldehyde groups (oxidized by periodate) with the amine-functionalized beads in the presence of sodium cyanoborohydride. 26257013 3 26 contain containing 595:604 arg2 groups 615:620 aldehyde groups (oxidized by periodate) 606:644 aldehyde groups (oxidized by periodate) 606:644 The first one was to block the primary amines in the peptides by addition of formaldehyde and sodium cyanoborohydride into the peptide sample, and the second one was to couple the glycopeptides onto solid phase beads by incubating the glycopeptides containing aldehyde groups (oxidized by periodate) with the amine-functionalized beads in the presence of sodium cyanoborohydride. 26257013 1 27 theme chemistry 113:121 arg1 method 123:128 An amine chemistry method 104:128 An amine chemistry method 104:128 An amine chemistry method was developed for the extraction of N-glycopeptides using amine-functionalized beads for glycoproteomics analysis. 26257013 6 28 theme conventional 1150:1161 arg1 method 1183:1188 the conventional hydrazide chemistry method 1146:1188 the conventional hydrazide chemistry method 1146:1188 It was found that this new method led to significant increase in the identification of N-glycosites compared with the conventional hydrazide chemistry method. 26257013 0 29 theme Selective 27:35 arg1 Enrichment 37:46 Selective Enrichment 27:46 Selective Enrichment of N-Linked Glycopeptides 27:72 Amine Chemistry Method for Selective Enrichment of N-Linked Glycopeptides for Glycoproteomics Analysis. 26257013 3 30 theme sodium 440:445 arg1 cyanoborohydride 447:462 sodium cyanoborohydride 440:462 sodium cyanoborohydride 440:462 The first one was to block the primary amines in the peptides by addition of formaldehyde and sodium cyanoborohydride into the peptide sample, and the second one was to couple the glycopeptides onto solid phase beads by incubating the glycopeptides containing aldehyde groups (oxidized by periodate) with the amine-functionalized beads in the presence of sodium cyanoborohydride. 26257013 3 31 from amines 385:390 arg1 peptides 399:406 the peptides 395:406 the peptides 395:406 The first one was to block the primary amines in the peptides by addition of formaldehyde and sodium cyanoborohydride into the peptide sample, and the second one was to couple the glycopeptides onto solid phase beads by incubating the glycopeptides containing aldehyde groups (oxidized by periodate) with the amine-functionalized beads in the presence of sodium cyanoborohydride. 26257013 4 32 theme prior 840:844 arg1 amination 821:829 the first reductive amination reaction 801:838 the first reductive amination reaction prior to the periodate oxidation 801:871 It was demonstrated that the blocking of primary amines in the peptides by the first reductive amination reaction prior to the periodate oxidation made the amine chemistry method very efficient and sensitive. 26257013 6 33 theme new 1055:1057 arg1 method 1059:1064 this new method 1050:1064 this new method 1050:1064 It was found that this new method led to significant increase in the identification of N-glycosites compared with the conventional hydrazide chemistry method. 26257013 0 34 theme N-Linked 51:58 arg1 Glycopeptides 60:72 N-Linked Glycopeptides 51:72 N-Linked Glycopeptides 51:72 Amine Chemistry Method for Selective Enrichment of N-Linked Glycopeptides for Glycoproteomics Analysis. 26257013 3 35 dep groups 615:620 arg1 oxidized 623:630 oxidized 623:630 oxidized by periodate 623:643 The first one was to block the primary amines in the peptides by addition of formaldehyde and sodium cyanoborohydride into the peptide sample, and the second one was to couple the glycopeptides onto solid phase beads by incubating the glycopeptides containing aldehyde groups (oxidized by periodate) with the amine-functionalized beads in the presence of sodium cyanoborohydride. 26257013 3 36 theme amine-functionalized 655:674 arg1 beads 676:680 the amine-functionalized beads 651:680 the amine-functionalized beads in the presence of sodium cyanoborohydride 651:723 The first one was to block the primary amines in the peptides by addition of formaldehyde and sodium cyanoborohydride into the peptide sample, and the second one was to couple the glycopeptides onto solid phase beads by incubating the glycopeptides containing aldehyde groups (oxidized by periodate) with the amine-functionalized beads in the presence of sodium cyanoborohydride. 26257013 3 37 theme aldehyde 606:613 arg1 groups 615:620 aldehyde groups (oxidized by periodate) 606:644 aldehyde groups (oxidized by periodate) 606:644 The first one was to block the primary amines in the peptides by addition of formaldehyde and sodium cyanoborohydride into the peptide sample, and the second one was to couple the glycopeptides onto solid phase beads by incubating the glycopeptides containing aldehyde groups (oxidized by periodate) with the amine-functionalized beads in the presence of sodium cyanoborohydride. 26257013 5 38 theme new 940:942 arg1 method 944:949 This new method 935:949 This new method 935:949 This new method was validated by analysis of glycoprotein standards as well as proteome samples. 26257013 3 39 theme formaldehyde 423:434 arg1 addition 411:418 addition 411:418 addition of formaldehyde and sodium cyanoborohydride 411:462 The first one was to block the primary amines in the peptides by addition of formaldehyde and sodium cyanoborohydride into the peptide sample, and the second one was to couple the glycopeptides onto solid phase beads by incubating the glycopeptides containing aldehyde groups (oxidized by periodate) with the amine-functionalized beads in the presence of sodium cyanoborohydride. 26257013 2 40 theme reductive 249:257 arg1 reactions 269:277 Two reductive amination reactions 245:277 Two reductive amination reactions between primary amine and aldehyde 245:312 Two reductive amination reactions between primary amine and aldehyde were employed in this approach. 26257013 3 41 gly glycopeptides 581:593 arg2 glycopeptides 581:593 the glycopeptides 577:593 the glycopeptides containing aldehyde groups (oxidized by periodate) 577:644 The first one was to block the primary amines in the peptides by addition of formaldehyde and sodium cyanoborohydride into the peptide sample, and the second one was to couple the glycopeptides onto solid phase beads by incubating the glycopeptides containing aldehyde groups (oxidized by periodate) with the amine-functionalized beads in the presence of sodium cyanoborohydride. 26257013 4 42 from blocking 755:762 arg1 peptides 789:796 the peptides 785:796 the peptides 785:796 It was demonstrated that the blocking of primary amines in the peptides by the first reductive amination reaction prior to the periodate oxidation made the amine chemistry method very efficient and sensitive. 26257013 1 43 gly N-glycopeptides 166:180 arg2 N-glycopeptides 166:180 N-glycopeptides 166:180 N-glycopeptides using amine-functionalized beads for glycoproteomics analysis 166:242 An amine chemistry method was developed for the extraction of N-glycopeptides using amine-functionalized beads for glycoproteomics analysis. 26257013 3 44 theme sodium 701:706 arg1 cyanoborohydride 708:723 sodium cyanoborohydride 701:723 sodium cyanoborohydride 701:723 The first one was to block the primary amines in the peptides by addition of formaldehyde and sodium cyanoborohydride into the peptide sample, and the second one was to couple the glycopeptides onto solid phase beads by incubating the glycopeptides containing aldehyde groups (oxidized by periodate) with the amine-functionalized beads in the presence of sodium cyanoborohydride. 26257013 4 45 theme reductive 811:819 arg1 amination 821:829 the first reductive amination reaction 801:838 the first reductive amination reaction prior to the periodate oxidation 801:871 It was demonstrated that the blocking of primary amines in the peptides by the first reductive amination reaction prior to the periodate oxidation made the amine chemistry method very efficient and sensitive. 26257013 4 46 theme first 805:809 arg1 amination 821:829 the first reductive amination reaction 801:838 the first reductive amination reaction prior to the periodate oxidation 801:871 It was demonstrated that the blocking of primary amines in the peptides by the first reductive amination reaction prior to the periodate oxidation made the amine chemistry method very efficient and sensitive. 26257013 5 47 gly glycoprotein 980:991 arg1 glycoprotein 980:991 glycoprotein standards 980:1001 glycoprotein standards as well as proteome samples 980:1029 This new method was validated by analysis of glycoprotein standards as well as proteome samples. 26257013 4 48 theme periodate 853:861 arg1 oxidation 863:871 the periodate oxidation 849:871 the periodate oxidation 849:871 It was demonstrated that the blocking of primary amines in the peptides by the first reductive amination reaction prior to the periodate oxidation made the amine chemistry method very efficient and sensitive. 26257013 4 49 dep amination 821:829 arg1 reaction 831:838 reaction 831:838 the first reductive amination reaction prior to the periodate oxidation 801:871 It was demonstrated that the blocking of primary amines in the peptides by the first reductive amination reaction prior to the periodate oxidation made the amine chemistry method very efficient and sensitive. 26257013 5 50 theme glycoprotein 980:991 arg1 standards 993:1001 glycoprotein standards 980:1001 glycoprotein standards as well as proteome samples 980:1029 This new method was validated by analysis of glycoprotein standards as well as proteome samples. 26257013 3 51 theme peptide 473:479 arg1 sample 481:486 the peptide sample 469:486 the peptide sample 469:486 The first one was to block the primary amines in the peptides by addition of formaldehyde and sodium cyanoborohydride into the peptide sample, and the second one was to couple the glycopeptides onto solid phase beads by incubating the glycopeptides containing aldehyde groups (oxidized by periodate) with the amine-functionalized beads in the presence of sodium cyanoborohydride. 26257013 0 52 theme Glycopeptides 60:72 arg1 Enrichment 37:46 Selective Enrichment 27:46 Selective Enrichment of N-Linked Glycopeptides 27:72 Amine Chemistry Method for Selective Enrichment of N-Linked Glycopeptides for Glycoproteomics Analysis. 26257013 6 53 theme chemistry 1173:1181 arg1 method 1183:1188 the conventional hydrazide chemistry method 1146:1188 the conventional hydrazide chemistry method 1146:1188 It was found that this new method led to significant increase in the identification of N-glycosites compared with the conventional hydrazide chemistry method. 26257013 2 54 theme primary 287:293 arg1 amine 295:299 primary amine 287:299 primary amine 287:299 Two reductive amination reactions between primary amine and aldehyde were employed in this approach. 26257013 6 55 theme N-glycosites 1119:1130 arg1 identification 1101:1114 the identification 1097:1114 the identification of N-glycosites 1097:1130 It was found that this new method led to significant increase in the identification of N-glycosites compared with the conventional hydrazide chemistry method. 28924033 14 0 theme important 2477:2485 arg1 link 2487:2490 an important link 2474:2490 an important link between the RGP and cell wall physiology of S. mutans 2474:2544 Our data demonstrate an important link between the RGP and cell wall physiology of S. mutans, affecting critical features used by the organism to cause disease and providing a potential novel target for inhibiting the pathogenesis of S. mutans. 28924033 12 1 theme loss 2251:2254 arg1 consequences 2231:2242 the consequences 2227:2242 the consequences of the loss of RgpF, a rhamnosyltransferase involved in RGP construction 2227:2315 The present study describes the consequences of the loss of RgpF, a rhamnosyltransferase involved in RGP construction. 28924033 6 2 theme tolerance 1066:1074 arg1 perturbation 953:964 a perturbation 951:964 a perturbation of membrane-associated functions known to be critical for aciduricity 951:1034 The loss of rgpF caused a perturbation of membrane-associated functions known to be critical for aciduricity, a hallmark of S. mutans acid tolerance. 28924033 6 2 theme tolerance 1066:1074 arg1 hallmark 1039:1046 a hallmark 1037:1046 a hallmark of S. mutans acid tolerance 1037:1074 The loss of rgpF caused a perturbation of membrane-associated functions known to be critical for aciduricity, a hallmark of S. mutans acid tolerance. 28924033 7 3 theme F1Fo 1197:1200 arg1 ATPase 1202:1207 the F1Fo ATPase 1193:1207 the F1Fo ATPase 1193:1207 The proton gradient across the membrane was disrupted, and the ΔrgpF mutant strain was unable to induce activity of the F1Fo ATPase in cultures grown under low-pH conditions. 28924033 2 4 attach linked 329:334 arg2 polysaccharide 308:321 a rhamnose-glucose polysaccharide 289:321 a rhamnose-glucose polysaccharide (RGP) linked to the peptidoglycan 289:355 In Streptococcus mutans, the cell wall is composed primarily of a rhamnose-glucose polysaccharide (RGP) linked to the peptidoglycan. 28924033 2 4 attach linked 329:334 arg1 peptidoglycan 343:355 the peptidoglycan 339:355 the peptidoglycan 339:355 In Streptococcus mutans, the cell wall is composed primarily of a rhamnose-glucose polysaccharide (RGP) linked to the peptidoglycan. 28924033 2 4 attach linked 329:334 arg2 RGP 324:326 RGP 324:326 RGP 324:326 In Streptococcus mutans, the cell wall is composed primarily of a rhamnose-glucose polysaccharide (RGP) linked to the peptidoglycan. 28924033 1 5 theme cellular 171:178 arg1 physiology 180:189 cellular physiology 171:189 cellular physiology 171:189 Bacterial cell wall dynamics have been implicated as important determinants of cellular physiology, stress tolerance, and virulence. 28924033 2 6 theme rhamnose-glucose 291:306 arg1 RGP 324:326 RGP 324:326 RGP 324:326 In Streptococcus mutans, the cell wall is composed primarily of a rhamnose-glucose polysaccharide (RGP) linked to the peptidoglycan. 28924033 2 6 theme rhamnose-glucose 291:306 arg1 polysaccharide 308:321 a rhamnose-glucose polysaccharide 289:321 a rhamnose-glucose polysaccharide (RGP) linked to the peptidoglycan 289:355 In Streptococcus mutans, the cell wall is composed primarily of a rhamnose-glucose polysaccharide (RGP) linked to the peptidoglycan. 28924033 5 7 theme stress-inducing 847:861 arg1 conditions 871:880 various stress-inducing culture conditions 839:880 various stress-inducing culture conditions 839:880 The ΔrgpF mutant strain displayed an overall reduced fitness compared to the wild type, with heightened sensitivities to various stress-inducing culture conditions and an inability to tolerate acid challenge. 28924033 9 8 theme infection 1685:1693 arg1 model 1695:1699 an in vivoGalleria mellonella infection model 1655:1699 an in vivoGalleria mellonella infection model 1655:1699 Additionally, the ΔrgpF mutant lost competitive fitness against oral peroxigenic streptococci, and it displayed significantly attenuated virulence in an in vivoGalleria mellonella infection model. 28924033 7 9 theme ATPase 1202:1207 arg1 activity 1181:1188 activity 1181:1188 activity of the F1Fo ATPase in cultures grown under low-pH conditions 1181:1249 The proton gradient across the membrane was disrupted, and the ΔrgpF mutant strain was unable to induce activity of the F1Fo ATPase in cultures grown under low-pH conditions. 28924033 1 10 theme tolerance 199:207 arg1 dynamics 112:119 Bacterial cell wall dynamics 92:119 Bacterial cell wall dynamics 92:119 Bacterial cell wall dynamics have been implicated as important determinants of cellular physiology, stress tolerance, and virulence. 28924033 1 10 theme tolerance 199:207 arg1 determinants 155:166 important determinants 145:166 important determinants of cellular physiology, stress tolerance, and virulence 145:222 Bacterial cell wall dynamics have been implicated as important determinants of cellular physiology, stress tolerance, and virulence. 28924033 8 11 theme less 1405:1408 arg1 biofilms 1417:1424 significantly less robust biofilms 1391:1424 significantly less robust biofilms 1391:1424 Further, the virulence potential of S. mutans was also drastically reduced following the deletion of rgpF The ΔrgpF mutant strain produced significantly less robust biofilms, indicating an impairment in its ability to adhere to hydroxyapatite surfaces. 28924033 10 12 theme overall 1793:1799 arg1 tolerance 1808:1816 overall stress tolerance 1793:1816 overall stress tolerance 1793:1816 Collectively, these results highlight a critical function of the RGP in the maintenance of overall stress tolerance and virulence traits in S. mutansIMPORTANCE The cell wall of Streptococcus mutans, the bacterium most commonly associated with tooth decay, is abundant in rhamnose-glucose polysaccharides (RGP). 28924033 5 13 theme heightened 811:820 arg1 sensitivities 822:834 heightened sensitivities 811:834 heightened sensitivities to various stress-inducing culture conditions 811:880 The ΔrgpF mutant strain displayed an overall reduced fitness compared to the wild type, with heightened sensitivities to various stress-inducing culture conditions and an inability to tolerate acid challenge. 28924033 14 14 theme potential 2629:2637 arg1 target 2645:2650 a potential novel target 2627:2650 a potential novel target for inhibiting the pathogenesis of S. mutans 2627:2695 Our data demonstrate an important link between the RGP and cell wall physiology of S. mutans, affecting critical features used by the organism to cause disease and providing a potential novel target for inhibiting the pathogenesis of S. mutans. 28924033 4 15 theme core 683:686 arg1 backbone 701:708 the core polyrhamnose backbone 679:708 the core polyrhamnose backbone of RGP 679:715 The present study characterizes the impact of RGP disruption as a result of the deletion of rgpF, the gene encoding a rhamnosyltransferase involved in the construction of the core polyrhamnose backbone of RGP. 28924033 7 16 from activity 1181:1188 arg1 cultures 1212:1219 cultures 1212:1219 cultures grown under low-pH conditions 1212:1249 The proton gradient across the membrane was disrupted, and the ΔrgpF mutant strain was unable to induce activity of the F1Fo ATPase in cultures grown under low-pH conditions. 28924033 4 17 theme backbone 701:708 arg1 construction 663:674 the construction 659:674 the construction of the core polyrhamnose backbone of RGP 659:715 The present study characterizes the impact of RGP disruption as a result of the deletion of rgpF, the gene encoding a rhamnosyltransferase involved in the construction of the core polyrhamnose backbone of RGP. 28924033 9 18 theme competitive 1541:1551 arg1 fitness 1553:1559 competitive fitness 1541:1559 competitive fitness against oral peroxigenic streptococci 1541:1597 Additionally, the ΔrgpF mutant lost competitive fitness against oral peroxigenic streptococci, and it displayed significantly attenuated virulence in an in vivoGalleria mellonella infection model. 28924033 13 19 theme fitness 2393:2399 arg1 ablation 2358:2365 severe ablation 2351:2365 severe ablation of the organism's overall fitness 2351:2399 The deletion of rgpF resulted in severe ablation of the organism's overall fitness, culminating in significantly attenuated virulence. 28924033 10 20 theme virulence 1822:1830 arg1 maintenance 1778:1788 the maintenance 1774:1788 the maintenance of overall stress tolerance and virulence traits in S. mutansIMPORTANCE 1774:1860 Collectively, these results highlight a critical function of the RGP in the maintenance of overall stress tolerance and virulence traits in S. mutansIMPORTANCE The cell wall of Streptococcus mutans, the bacterium most commonly associated with tooth decay, is abundant in rhamnose-glucose polysaccharides (RGP). 28924033 5 21 theme acid 911:914 arg1 challenge 916:924 acid challenge 911:924 acid challenge 911:924 The ΔrgpF mutant strain displayed an overall reduced fitness compared to the wild type, with heightened sensitivities to various stress-inducing culture conditions and an inability to tolerate acid challenge. 28924033 12 22 theme RGP 2300:2302 arg1 construction 2304:2315 RGP construction 2300:2315 RGP construction 2300:2315 The present study describes the consequences of the loss of RgpF, a rhamnosyltransferase involved in RGP construction. 28924033 5 23 theme mutant 728:733 arg1 strain 735:740 The ΔrgpF mutant strain 718:740 The ΔrgpF mutant strain 718:740 The ΔrgpF mutant strain displayed an overall reduced fitness compared to the wild type, with heightened sensitivities to various stress-inducing culture conditions and an inability to tolerate acid challenge. 28924033 10 24 theme tolerance 1808:1816 arg1 maintenance 1778:1788 the maintenance 1774:1788 the maintenance of overall stress tolerance and virulence traits in S. mutansIMPORTANCE 1774:1860 Collectively, these results highlight a critical function of the RGP in the maintenance of overall stress tolerance and virulence traits in S. mutansIMPORTANCE The cell wall of Streptococcus mutans, the bacterium most commonly associated with tooth decay, is abundant in rhamnose-glucose polysaccharides (RGP). 28924033 14 25 theme critical 2557:2564 arg1 features 2566:2573 critical features 2557:2573 critical features used by the organism to cause disease 2557:2611 Our data demonstrate an important link between the RGP and cell wall physiology of S. mutans, affecting critical features used by the organism to cause disease and providing a potential novel target for inhibiting the pathogenesis of S. mutans. 28924033 12 26 theme RgpF 2259:2262 arg1 loss 2251:2254 the loss 2247:2254 the loss of RgpF, a rhamnosyltransferase involved in RGP construction 2247:2315 The present study describes the consequences of the loss of RgpF, a rhamnosyltransferase involved in RGP construction. 28924033 6 27 theme membrane-associated 969:987 arg1 functions 989:997 membrane-associated functions 969:997 membrane-associated functions known to be critical for aciduricity 969:1034 The loss of rgpF caused a perturbation of membrane-associated functions known to be critical for aciduricity, a hallmark of S. mutans acid tolerance. 28924033 8 28 from impairment 1441:1450 arg1 ability 1459:1465 its ability to adhere to hydroxyapatite surfaces 1455:1502 its ability to adhere to hydroxyapatite surfaces 1455:1502 Further, the virulence potential of S. mutans was also drastically reduced following the deletion of rgpF The ΔrgpF mutant strain produced significantly less robust biofilms, indicating an impairment in its ability to adhere to hydroxyapatite surfaces. 28924033 14 29 dep demonstrate 2462:2472 arg1 affecting 2547:2555 affecting 2547:2555 affecting critical features used by the organism to cause disease 2547:2611 Our data demonstrate an important link between the RGP and cell wall physiology of S. mutans, affecting critical features used by the organism to cause disease and providing a potential novel target for inhibiting the pathogenesis of S. mutans. 28924033 14 29 dep demonstrate 2462:2472 arg1 providing 2617:2625 providing 2617:2625 providing a potential novel target for inhibiting the pathogenesis of S. mutans 2617:2695 Our data demonstrate an important link between the RGP and cell wall physiology of S. mutans, affecting critical features used by the organism to cause disease and providing a potential novel target for inhibiting the pathogenesis of S. mutans. 28924033 10 30 dep highlight 1730:1738 arg1 wall 1871:1874 The cell wall 1862:1874 The cell wall of Streptococcus mutans, the bacterium most commonly associated with tooth decay, 1862:1956 Collectively, these results highlight a critical function of the RGP in the maintenance of overall stress tolerance and virulence traits in S. mutansIMPORTANCE The cell wall of Streptococcus mutans, the bacterium most commonly associated with tooth decay, is abundant in rhamnose-glucose polysaccharides (RGP). 28924033 10 30 dep highlight 1730:1738 arg1 abundant 1961:1968 abundant 1961:1968 abundant 1961:1968 Collectively, these results highlight a critical function of the RGP in the maintenance of overall stress tolerance and virulence traits in S. mutansIMPORTANCE The cell wall of Streptococcus mutans, the bacterium most commonly associated with tooth decay, is abundant in rhamnose-glucose polysaccharides (RGP). 28924033 3 31 theme potential 430:438 arg1 roles 440:444 the potential roles 426:444 the potential roles for RGP in S. mutans biology 426:473 Despite extensive studies describing its formation and composition, the potential roles for RGP in S. mutans biology have not been well investigated. 28924033 10 32 from abundant 1961:1968 arg1 RGP 2007:2009 RGP 2007:2009 RGP 2007:2009 Collectively, these results highlight a critical function of the RGP in the maintenance of overall stress tolerance and virulence traits in S. mutansIMPORTANCE The cell wall of Streptococcus mutans, the bacterium most commonly associated with tooth decay, is abundant in rhamnose-glucose polysaccharides (RGP). 28924033 10 32 from abundant 1961:1968 arg1 polysaccharides 1990:2004 rhamnose-glucose polysaccharides 1973:2004 rhamnose-glucose polysaccharides (RGP) 1973:2010 Collectively, these results highlight a critical function of the RGP in the maintenance of overall stress tolerance and virulence traits in S. mutansIMPORTANCE The cell wall of Streptococcus mutans, the bacterium most commonly associated with tooth decay, is abundant in rhamnose-glucose polysaccharides (RGP). 28924033 9 33 theme ΔrgpF 1523:1527 arg1 mutant 1529:1534 the ΔrgpF mutant 1519:1534 the ΔrgpF mutant 1519:1534 Additionally, the ΔrgpF mutant lost competitive fitness against oral peroxigenic streptococci, and it displayed significantly attenuated virulence in an in vivoGalleria mellonella infection model. 28924033 6 34 theme S. 1051:1052 arg1 tolerance 1066:1074 S. mutans acid tolerance 1051:1074 S. mutans acid tolerance 1051:1074 The loss of rgpF caused a perturbation of membrane-associated functions known to be critical for aciduricity, a hallmark of S. mutans acid tolerance. 28924033 0 35 from Maintenance 21:31 arg1 mutans 84:89 Streptococcus mutans 70:89 Streptococcus mutans 70:89 RgpF Is Required for Maintenance of Stress Tolerance and Virulence in Streptococcus mutans. 28924033 0 36 theme Virulence 57:65 arg1 Maintenance 21:31 Maintenance 21:31 Maintenance of Stress Tolerance and Virulence in Streptococcus mutans 21:89 RgpF Is Required for Maintenance of Stress Tolerance and Virulence in Streptococcus mutans. 28924033 4 37 theme RGP 713:715 arg1 backbone 701:708 the core polyrhamnose backbone 679:708 the core polyrhamnose backbone of RGP 679:715 The present study characterizes the impact of RGP disruption as a result of the deletion of rgpF, the gene encoding a rhamnosyltransferase involved in the construction of the core polyrhamnose backbone of RGP. 28924033 7 38 theme mutant 1146:1151 arg1 unable 1164:1169 unable 1164:1169 unable 1164:1169 The proton gradient across the membrane was disrupted, and the ΔrgpF mutant strain was unable to induce activity of the F1Fo ATPase in cultures grown under low-pH conditions. 28924033 7 38 theme mutant 1146:1151 arg1 strain 1153:1158 the ΔrgpF mutant strain 1136:1158 the ΔrgpF mutant strain 1136:1158 The proton gradient across the membrane was disrupted, and the ΔrgpF mutant strain was unable to induce activity of the F1Fo ATPase in cultures grown under low-pH conditions. 28924033 13 39 theme overall 2385:2391 arg1 fitness 2393:2399 the organism's overall fitness 2370:2399 the organism's overall fitness 2370:2399 The deletion of rgpF resulted in severe ablation of the organism's overall fitness, culminating in significantly attenuated virulence. 28924033 12 40 theme present 2203:2209 arg1 study 2211:2215 The present study 2199:2215 The present study 2199:2215 The present study describes the consequences of the loss of RgpF, a rhamnosyltransferase involved in RGP construction. 28924033 5 41 theme wild 795:798 arg1 type 800:803 the wild type 791:803 the wild type 791:803 The ΔrgpF mutant strain displayed an overall reduced fitness compared to the wild type, with heightened sensitivities to various stress-inducing culture conditions and an inability to tolerate acid challenge. 28924033 1 42 theme cell 102:105 arg1 dynamics 112:119 Bacterial cell wall dynamics 92:119 Bacterial cell wall dynamics 92:119 Bacterial cell wall dynamics have been implicated as important determinants of cellular physiology, stress tolerance, and virulence. 28924033 1 42 theme cell 102:105 arg1 determinants 155:166 important determinants 145:166 important determinants of cellular physiology, stress tolerance, and virulence 145:222 Bacterial cell wall dynamics have been implicated as important determinants of cellular physiology, stress tolerance, and virulence. 28924033 8 43 theme rgpF 1353:1356 arg1 deletion 1341:1348 the deletion 1337:1348 the deletion of rgpF 1337:1356 Further, the virulence potential of S. mutans was also drastically reduced following the deletion of rgpF The ΔrgpF mutant strain produced significantly less robust biofilms, indicating an impairment in its ability to adhere to hydroxyapatite surfaces. 28924033 5 44 theme overall 755:761 arg1 fitness 771:777 an overall reduced fitness 752:777 an overall reduced fitness 752:777 The ΔrgpF mutant strain displayed an overall reduced fitness compared to the wild type, with heightened sensitivities to various stress-inducing culture conditions and an inability to tolerate acid challenge. 28924033 14 45 theme wall 2517:2520 arg1 physiology 2522:2531 the RGP and cell wall physiology 2500:2531 physiology 2522:2531 Our data demonstrate an important link between the RGP and cell wall physiology of S. mutans, affecting critical features used by the organism to cause disease and providing a potential novel target for inhibiting the pathogenesis of S. mutans. 28924033 9 46 theme oral 1569:1572 arg1 streptococci 1586:1597 oral peroxigenic streptococci 1569:1597 oral peroxigenic streptococci 1569:1597 Additionally, the ΔrgpF mutant lost competitive fitness against oral peroxigenic streptococci, and it displayed significantly attenuated virulence in an in vivoGalleria mellonella infection model. 28924033 8 47 theme ΔrgpF 1362:1366 arg1 strain 1375:1380 The ΔrgpF mutant strain 1358:1380 The ΔrgpF mutant strain 1358:1380 Further, the virulence potential of S. mutans was also drastically reduced following the deletion of rgpF The ΔrgpF mutant strain produced significantly less robust biofilms, indicating an impairment in its ability to adhere to hydroxyapatite surfaces. 28924033 9 48 dep in 1658:1659 arg1 vivoGalleria 1661:1672 vivoGalleria 1661:1672 vivoGalleria 1661:1672 Additionally, the ΔrgpF mutant lost competitive fitness against oral peroxigenic streptococci, and it displayed significantly attenuated virulence in an in vivoGalleria mellonella infection model. 28924033 3 49 theme mutans 460:465 arg1 biology 467:473 S. mutans biology 457:473 S. mutans biology 457:473 Despite extensive studies describing its formation and composition, the potential roles for RGP in S. mutans biology have not been well investigated. 28924033 1 50 theme virulence 214:222 arg1 dynamics 112:119 Bacterial cell wall dynamics 92:119 Bacterial cell wall dynamics 92:119 Bacterial cell wall dynamics have been implicated as important determinants of cellular physiology, stress tolerance, and virulence. 28924033 1 50 theme virulence 214:222 arg1 determinants 155:166 important determinants 145:166 important determinants of cellular physiology, stress tolerance, and virulence 145:222 Bacterial cell wall dynamics have been implicated as important determinants of cellular physiology, stress tolerance, and virulence. 28924033 10 51 theme cell 1866:1869 arg1 wall 1871:1874 The cell wall 1862:1874 The cell wall of Streptococcus mutans, the bacterium most commonly associated with tooth decay, 1862:1956 Collectively, these results highlight a critical function of the RGP in the maintenance of overall stress tolerance and virulence traits in S. mutansIMPORTANCE The cell wall of Streptococcus mutans, the bacterium most commonly associated with tooth decay, is abundant in rhamnose-glucose polysaccharides (RGP). 28924033 10 51 theme cell 1866:1869 arg1 abundant 1961:1968 abundant 1961:1968 abundant 1961:1968 Collectively, these results highlight a critical function of the RGP in the maintenance of overall stress tolerance and virulence traits in S. mutansIMPORTANCE The cell wall of Streptococcus mutans, the bacterium most commonly associated with tooth decay, is abundant in rhamnose-glucose polysaccharides (RGP). 28924033 5 52 theme reduced 763:769 arg1 fitness 771:777 an overall reduced fitness 752:777 an overall reduced fitness 752:777 The ΔrgpF mutant strain displayed an overall reduced fitness compared to the wild type, with heightened sensitivities to various stress-inducing culture conditions and an inability to tolerate acid challenge. 28924033 13 53 theme severe 2351:2356 arg1 ablation 2358:2365 severe ablation 2351:2365 severe ablation of the organism's overall fitness 2351:2399 The deletion of rgpF resulted in severe ablation of the organism's overall fitness, culminating in significantly attenuated virulence. 28924033 4 54 theme deletion 588:595 arg1 impact 544:549 the impact 540:549 the impact of RGP disruption 540:567 The present study characterizes the impact of RGP disruption as a result of the deletion of rgpF, the gene encoding a rhamnosyltransferase involved in the construction of the core polyrhamnose backbone of RGP. 28924033 4 54 theme deletion 588:595 arg1 result 574:579 a result 572:579 a result of the deletion of rgpF, the gene encoding a rhamnosyltransferase involved in the construction of the core polyrhamnose backbone of RGP 572:715 The present study characterizes the impact of RGP disruption as a result of the deletion of rgpF, the gene encoding a rhamnosyltransferase involved in the construction of the core polyrhamnose backbone of RGP. 28924033 3 55 from roles 440:444 arg1 biology 467:473 S. mutans biology 457:473 S. mutans biology 457:473 Despite extensive studies describing its formation and composition, the potential roles for RGP in S. mutans biology have not been well investigated. 28924033 9 56 theme attenuated 1631:1640 arg1 virulence 1642:1650 significantly attenuated virulence 1617:1650 significantly attenuated virulence 1617:1650 Additionally, the ΔrgpF mutant lost competitive fitness against oral peroxigenic streptococci, and it displayed significantly attenuated virulence in an in vivoGalleria mellonella infection model. 28924033 6 57 theme acid 1061:1064 arg1 tolerance 1066:1074 S. mutans acid tolerance 1051:1074 S. mutans acid tolerance 1051:1074 The loss of rgpF caused a perturbation of membrane-associated functions known to be critical for aciduricity, a hallmark of S. mutans acid tolerance. 28924033 4 58 theme disruption 558:567 arg1 impact 544:549 the impact 540:549 the impact of RGP disruption 540:567 The present study characterizes the impact of RGP disruption as a result of the deletion of rgpF, the gene encoding a rhamnosyltransferase involved in the construction of the core polyrhamnose backbone of RGP. 28924033 4 58 theme disruption 558:567 arg1 result 574:579 a result 572:579 a result of the deletion of rgpF, the gene encoding a rhamnosyltransferase involved in the construction of the core polyrhamnose backbone of RGP 572:715 The present study characterizes the impact of RGP disruption as a result of the deletion of rgpF, the gene encoding a rhamnosyltransferase involved in the construction of the core polyrhamnose backbone of RGP. 28924033 10 59 theme mutans 1893:1898 arg1 wall 1871:1874 The cell wall 1862:1874 The cell wall of Streptococcus mutans, the bacterium most commonly associated with tooth decay, 1862:1956 Collectively, these results highlight a critical function of the RGP in the maintenance of overall stress tolerance and virulence traits in S. mutansIMPORTANCE The cell wall of Streptococcus mutans, the bacterium most commonly associated with tooth decay, is abundant in rhamnose-glucose polysaccharides (RGP). 28924033 10 59 theme mutans 1893:1898 arg1 abundant 1961:1968 abundant 1961:1968 abundant 1961:1968 Collectively, these results highlight a critical function of the RGP in the maintenance of overall stress tolerance and virulence traits in S. mutansIMPORTANCE The cell wall of Streptococcus mutans, the bacterium most commonly associated with tooth decay, is abundant in rhamnose-glucose polysaccharides (RGP). 28924033 7 60 theme proton 1081:1086 arg1 gradient 1088:1095 The proton gradient 1077:1095 The proton gradient across the membrane 1077:1115 The proton gradient across the membrane was disrupted, and the ΔrgpF mutant strain was unable to induce activity of the F1Fo ATPase in cultures grown under low-pH conditions. 28924033 10 61 theme critical 1742:1749 arg1 function 1751:1758 a critical function 1740:1758 a critical function of the RGP 1740:1769 Collectively, these results highlight a critical function of the RGP in the maintenance of overall stress tolerance and virulence traits in S. mutansIMPORTANCE The cell wall of Streptococcus mutans, the bacterium most commonly associated with tooth decay, is abundant in rhamnose-glucose polysaccharides (RGP). 28924033 1 62 theme physiology 180:189 arg1 dynamics 112:119 Bacterial cell wall dynamics 92:119 Bacterial cell wall dynamics 92:119 Bacterial cell wall dynamics have been implicated as important determinants of cellular physiology, stress tolerance, and virulence. 28924033 1 62 theme physiology 180:189 arg1 determinants 155:166 important determinants 145:166 important determinants of cellular physiology, stress tolerance, and virulence 145:222 Bacterial cell wall dynamics have been implicated as important determinants of cellular physiology, stress tolerance, and virulence. 28924033 0 63 theme Stress 36:41 arg1 Tolerance 43:51 Stress Tolerance 36:51 Stress Tolerance 36:51 RgpF Is Required for Maintenance of Stress Tolerance and Virulence in Streptococcus mutans. 28924033 9 64 theme in 1658:1659 arg1 model 1695:1699 an in vivoGalleria mellonella infection model 1655:1699 an in vivoGalleria mellonella infection model 1655:1699 Additionally, the ΔrgpF mutant lost competitive fitness against oral peroxigenic streptococci, and it displayed significantly attenuated virulence in an in vivoGalleria mellonella infection model. 28924033 10 65 dep tolerance 1808:1816 arg1 traits 1832:1837 traits 1832:1837 traits 1832:1837 Collectively, these results highlight a critical function of the RGP in the maintenance of overall stress tolerance and virulence traits in S. mutansIMPORTANCE The cell wall of Streptococcus mutans, the bacterium most commonly associated with tooth decay, is abundant in rhamnose-glucose polysaccharides (RGP). 28924033 5 66 theme various 839:845 arg1 conditions 871:880 various stress-inducing culture conditions 839:880 various stress-inducing culture conditions 839:880 The ΔrgpF mutant strain displayed an overall reduced fitness compared to the wild type, with heightened sensitivities to various stress-inducing culture conditions and an inability to tolerate acid challenge. 28924033 9 67 theme mellonella 1674:1683 arg1 model 1695:1699 an in vivoGalleria mellonella infection model 1655:1699 an in vivoGalleria mellonella infection model 1655:1699 Additionally, the ΔrgpF mutant lost competitive fitness against oral peroxigenic streptococci, and it displayed significantly attenuated virulence in an in vivoGalleria mellonella infection model. 28924033 10 68 theme RGP 1767:1769 arg1 function 1751:1758 a critical function 1740:1758 a critical function of the RGP 1740:1769 Collectively, these results highlight a critical function of the RGP in the maintenance of overall stress tolerance and virulence traits in S. mutansIMPORTANCE The cell wall of Streptococcus mutans, the bacterium most commonly associated with tooth decay, is abundant in rhamnose-glucose polysaccharides (RGP). 28924033 1 69 theme stress 192:197 arg1 tolerance 199:207 stress tolerance 192:207 stress tolerance 192:207 Bacterial cell wall dynamics have been implicated as important determinants of cellular physiology, stress tolerance, and virulence. 28924033 6 70 theme rgpF 939:942 arg1 loss 931:934 The loss 927:934 The loss of rgpF 927:942 The loss of rgpF caused a perturbation of membrane-associated functions known to be critical for aciduricity, a hallmark of S. mutans acid tolerance. 28924033 8 71 theme robust 1410:1415 arg1 biofilms 1417:1424 significantly less robust biofilms 1391:1424 significantly less robust biofilms 1391:1424 Further, the virulence potential of S. mutans was also drastically reduced following the deletion of rgpF The ΔrgpF mutant strain produced significantly less robust biofilms, indicating an impairment in its ability to adhere to hydroxyapatite surfaces. 28924033 4 72 theme rgpF 600:603 arg1 deletion 588:595 the deletion 584:595 the deletion of rgpF, the gene encoding a rhamnosyltransferase involved in the construction of the core polyrhamnose backbone of RGP 584:715 The present study characterizes the impact of RGP disruption as a result of the deletion of rgpF, the gene encoding a rhamnosyltransferase involved in the construction of the core polyrhamnose backbone of RGP. 28924033 10 73 theme tooth 1945:1949 arg1 decay 1951:1955 tooth decay 1945:1955 tooth decay 1945:1955 Collectively, these results highlight a critical function of the RGP in the maintenance of overall stress tolerance and virulence traits in S. mutansIMPORTANCE The cell wall of Streptococcus mutans, the bacterium most commonly associated with tooth decay, is abundant in rhamnose-glucose polysaccharides (RGP). 28924033 2 74 theme Streptococcus 228:240 arg1 mutans 242:247 Streptococcus mutans 228:247 Streptococcus mutans 228:247 In Streptococcus mutans, the cell wall is composed primarily of a rhamnose-glucose polysaccharide (RGP) linked to the peptidoglycan. 28924033 10 75 theme rhamnose-glucose 1973:1988 arg1 RGP 2007:2009 RGP 2007:2009 RGP 2007:2009 Collectively, these results highlight a critical function of the RGP in the maintenance of overall stress tolerance and virulence traits in S. mutansIMPORTANCE The cell wall of Streptococcus mutans, the bacterium most commonly associated with tooth decay, is abundant in rhamnose-glucose polysaccharides (RGP). 28924033 10 75 theme rhamnose-glucose 1973:1988 arg1 polysaccharides 1990:2004 rhamnose-glucose polysaccharides 1973:2004 rhamnose-glucose polysaccharides (RGP) 1973:2010 Collectively, these results highlight a critical function of the RGP in the maintenance of overall stress tolerance and virulence traits in S. mutansIMPORTANCE The cell wall of Streptococcus mutans, the bacterium most commonly associated with tooth decay, is abundant in rhamnose-glucose polysaccharides (RGP). 28924033 1 76 theme wall 107:110 arg1 dynamics 112:119 Bacterial cell wall dynamics 92:119 Bacterial cell wall dynamics 92:119 Bacterial cell wall dynamics have been implicated as important determinants of cellular physiology, stress tolerance, and virulence. 28924033 1 76 theme wall 107:110 arg1 determinants 155:166 important determinants 145:166 important determinants of cellular physiology, stress tolerance, and virulence 145:222 Bacterial cell wall dynamics have been implicated as important determinants of cellular physiology, stress tolerance, and virulence. 28924033 2 77 theme cell 254:257 arg1 wall 259:262 the cell wall 250:262 the cell wall 250:262 In Streptococcus mutans, the cell wall is composed primarily of a rhamnose-glucose polysaccharide (RGP) linked to the peptidoglycan. 28924033 4 78 theme polyrhamnose 688:699 arg1 backbone 701:708 the core polyrhamnose backbone 679:708 the core polyrhamnose backbone of RGP 679:715 The present study characterizes the impact of RGP disruption as a result of the deletion of rgpF, the gene encoding a rhamnosyltransferase involved in the construction of the core polyrhamnose backbone of RGP. 28924033 5 79 theme ΔrgpF 722:726 arg1 strain 735:740 The ΔrgpF mutant strain 718:740 The ΔrgpF mutant strain 718:740 The ΔrgpF mutant strain displayed an overall reduced fitness compared to the wild type, with heightened sensitivities to various stress-inducing culture conditions and an inability to tolerate acid challenge. 28924033 5 80 theme culture 863:869 arg1 conditions 871:880 various stress-inducing culture conditions 839:880 various stress-inducing culture conditions 839:880 The ΔrgpF mutant strain displayed an overall reduced fitness compared to the wild type, with heightened sensitivities to various stress-inducing culture conditions and an inability to tolerate acid challenge. 28924033 8 81 theme virulence 1265:1273 arg1 potential 1275:1283 the virulence potential 1261:1283 the virulence potential of S. mutans 1261:1296 Further, the virulence potential of S. mutans was also drastically reduced following the deletion of rgpF The ΔrgpF mutant strain produced significantly less robust biofilms, indicating an impairment in its ability to adhere to hydroxyapatite surfaces. 28924033 0 82 theme Streptococcus 70:82 arg1 mutans 84:89 Streptococcus mutans 70:89 Streptococcus mutans 70:89 RgpF Is Required for Maintenance of Stress Tolerance and Virulence in Streptococcus mutans. 28924033 1 83 theme important 145:153 arg1 dynamics 112:119 Bacterial cell wall dynamics 92:119 Bacterial cell wall dynamics 92:119 Bacterial cell wall dynamics have been implicated as important determinants of cellular physiology, stress tolerance, and virulence. 28924033 1 83 theme important 145:153 arg1 determinants 155:166 important determinants 145:166 important determinants of cellular physiology, stress tolerance, and virulence 145:222 Bacterial cell wall dynamics have been implicated as important determinants of cellular physiology, stress tolerance, and virulence. 28924033 6 84 theme functions 989:997 arg1 perturbation 953:964 a perturbation 951:964 a perturbation of membrane-associated functions known to be critical for aciduricity 951:1034 The loss of rgpF caused a perturbation of membrane-associated functions known to be critical for aciduricity, a hallmark of S. mutans acid tolerance. 28924033 6 84 theme functions 989:997 arg1 hallmark 1039:1046 a hallmark 1037:1046 a hallmark of S. mutans acid tolerance 1037:1074 The loss of rgpF caused a perturbation of membrane-associated functions known to be critical for aciduricity, a hallmark of S. mutans acid tolerance. 28924033 14 85 theme mutans 2539:2544 arg1 RGP 2504:2506 the RGP and cell wall physiology 2500:2531 RGP 2504:2506 Our data demonstrate an important link between the RGP and cell wall physiology of S. mutans, affecting critical features used by the organism to cause disease and providing a potential novel target for inhibiting the pathogenesis of S. mutans. 28924033 14 85 theme mutans 2539:2544 arg1 physiology 2522:2531 the RGP and cell wall physiology 2500:2531 physiology 2522:2531 Our data demonstrate an important link between the RGP and cell wall physiology of S. mutans, affecting critical features used by the organism to cause disease and providing a potential novel target for inhibiting the pathogenesis of S. mutans. 28924033 8 86 theme hydroxyapatite 1480:1493 arg1 surfaces 1495:1502 hydroxyapatite surfaces 1480:1502 hydroxyapatite surfaces 1480:1502 Further, the virulence potential of S. mutans was also drastically reduced following the deletion of rgpF The ΔrgpF mutant strain produced significantly less robust biofilms, indicating an impairment in its ability to adhere to hydroxyapatite surfaces. 28924033 8 87 theme mutans 1291:1296 arg1 potential 1275:1283 the virulence potential 1261:1283 the virulence potential of S. mutans 1261:1296 Further, the virulence potential of S. mutans was also drastically reduced following the deletion of rgpF The ΔrgpF mutant strain produced significantly less robust biofilms, indicating an impairment in its ability to adhere to hydroxyapatite surfaces. 28924033 10 88 from maintenance 1778:1788 arg1 mutansIMPORTANCE 1845:1860 S. mutansIMPORTANCE 1842:1860 S. mutansIMPORTANCE 1842:1860 Collectively, these results highlight a critical function of the RGP in the maintenance of overall stress tolerance and virulence traits in S. mutansIMPORTANCE The cell wall of Streptococcus mutans, the bacterium most commonly associated with tooth decay, is abundant in rhamnose-glucose polysaccharides (RGP). 28924033 6 89 theme mutans 1054:1059 arg1 tolerance 1066:1074 S. mutans acid tolerance 1051:1074 S. mutans acid tolerance 1051:1074 The loss of rgpF caused a perturbation of membrane-associated functions known to be critical for aciduricity, a hallmark of S. mutans acid tolerance. 28924033 7 90 theme ΔrgpF 1140:1144 arg1 unable 1164:1169 unable 1164:1169 unable 1164:1169 The proton gradient across the membrane was disrupted, and the ΔrgpF mutant strain was unable to induce activity of the F1Fo ATPase in cultures grown under low-pH conditions. 28924033 7 90 theme ΔrgpF 1140:1144 arg1 strain 1153:1158 the ΔrgpF mutant strain 1136:1158 the ΔrgpF mutant strain 1136:1158 The proton gradient across the membrane was disrupted, and the ΔrgpF mutant strain was unable to induce activity of the F1Fo ATPase in cultures grown under low-pH conditions. 28924033 10 91 from polysaccharides 1990:2004 arg1 wall 1871:1874 The cell wall 1862:1874 The cell wall of Streptococcus mutans, the bacterium most commonly associated with tooth decay, 1862:1956 Collectively, these results highlight a critical function of the RGP in the maintenance of overall stress tolerance and virulence traits in S. mutansIMPORTANCE The cell wall of Streptococcus mutans, the bacterium most commonly associated with tooth decay, is abundant in rhamnose-glucose polysaccharides (RGP). 28924033 10 91 from polysaccharides 1990:2004 arg1 abundant 1961:1968 abundant 1961:1968 abundant 1961:1968 Collectively, these results highlight a critical function of the RGP in the maintenance of overall stress tolerance and virulence traits in S. mutansIMPORTANCE The cell wall of Streptococcus mutans, the bacterium most commonly associated with tooth decay, is abundant in rhamnose-glucose polysaccharides (RGP). 28924033 1 92 theme Bacterial 92:100 arg1 dynamics 112:119 Bacterial cell wall dynamics 92:119 Bacterial cell wall dynamics 92:119 Bacterial cell wall dynamics have been implicated as important determinants of cellular physiology, stress tolerance, and virulence. 28924033 1 92 theme Bacterial 92:100 arg1 determinants 155:166 important determinants 145:166 important determinants of cellular physiology, stress tolerance, and virulence 145:222 Bacterial cell wall dynamics have been implicated as important determinants of cellular physiology, stress tolerance, and virulence. 28924033 10 93 theme stress 1801:1806 arg1 tolerance 1808:1816 overall stress tolerance 1793:1816 overall stress tolerance 1793:1816 Collectively, these results highlight a critical function of the RGP in the maintenance of overall stress tolerance and virulence traits in S. mutansIMPORTANCE The cell wall of Streptococcus mutans, the bacterium most commonly associated with tooth decay, is abundant in rhamnose-glucose polysaccharides (RGP). 28924033 14 94 theme novel 2639:2643 arg1 target 2645:2650 a potential novel target 2627:2650 a potential novel target for inhibiting the pathogenesis of S. mutans 2627:2695 Our data demonstrate an important link between the RGP and cell wall physiology of S. mutans, affecting critical features used by the organism to cause disease and providing a potential novel target for inhibiting the pathogenesis of S. mutans. 28924033 3 95 theme extensive 366:374 arg1 studies 376:382 extensive studies 366:382 extensive studies describing its formation and composition 366:423 Despite extensive studies describing its formation and composition, the potential roles for RGP in S. mutans biology have not been well investigated. 28924033 4 96 theme RGP 554:556 arg1 disruption 558:567 RGP disruption 554:567 RGP disruption 554:567 The present study characterizes the impact of RGP disruption as a result of the deletion of rgpF, the gene encoding a rhamnosyltransferase involved in the construction of the core polyrhamnose backbone of RGP. 28924033 3 97 theme S. 457:458 arg1 biology 467:473 S. mutans biology 457:473 S. mutans biology 457:473 Despite extensive studies describing its formation and composition, the potential roles for RGP in S. mutans biology have not been well investigated. 28924033 14 98 theme mutans 2690:2695 arg1 pathogenesis 2671:2682 the pathogenesis 2667:2682 the pathogenesis of S. mutans 2667:2695 Our data demonstrate an important link between the RGP and cell wall physiology of S. mutans, affecting critical features used by the organism to cause disease and providing a potential novel target for inhibiting the pathogenesis of S. mutans. 28924033 4 99 theme present 512:518 arg1 study 520:524 The present study 508:524 The present study 508:524 The present study characterizes the impact of RGP disruption as a result of the deletion of rgpF, the gene encoding a rhamnosyltransferase involved in the construction of the core polyrhamnose backbone of RGP. 28924033 10 100 theme S. 1842:1843 arg1 mutansIMPORTANCE 1845:1860 S. mutansIMPORTANCE 1842:1860 S. mutansIMPORTANCE 1842:1860 Collectively, these results highlight a critical function of the RGP in the maintenance of overall stress tolerance and virulence traits in S. mutansIMPORTANCE The cell wall of Streptococcus mutans, the bacterium most commonly associated with tooth decay, is abundant in rhamnose-glucose polysaccharides (RGP). 28924033 0 101 theme Tolerance 43:51 arg1 Maintenance 21:31 Maintenance 21:31 Maintenance of Stress Tolerance and Virulence in Streptococcus mutans 21:89 RgpF Is Required for Maintenance of Stress Tolerance and Virulence in Streptococcus mutans. 28924033 14 102 theme cell 2512:2515 arg1 physiology 2522:2531 the RGP and cell wall physiology 2500:2531 physiology 2522:2531 Our data demonstrate an important link between the RGP and cell wall physiology of S. mutans, affecting critical features used by the organism to cause disease and providing a potential novel target for inhibiting the pathogenesis of S. mutans. 28924033 9 103 theme peroxigenic 1574:1584 arg1 streptococci 1586:1597 oral peroxigenic streptococci 1569:1597 oral peroxigenic streptococci 1569:1597 Additionally, the ΔrgpF mutant lost competitive fitness against oral peroxigenic streptococci, and it displayed significantly attenuated virulence in an in vivoGalleria mellonella infection model. 28924033 7 104 theme low-pH 1233:1238 arg1 conditions 1240:1249 low-pH conditions 1233:1249 low-pH conditions 1233:1249 The proton gradient across the membrane was disrupted, and the ΔrgpF mutant strain was unable to induce activity of the F1Fo ATPase in cultures grown under low-pH conditions. 28924033 13 105 theme rgpF 2334:2337 arg1 deletion 2322:2329 The deletion 2318:2329 The deletion of rgpF 2318:2337 The deletion of rgpF resulted in severe ablation of the organism's overall fitness, culminating in significantly attenuated virulence. 28924033 13 106 theme attenuated 2431:2440 arg1 virulence 2442:2450 significantly attenuated virulence 2417:2450 significantly attenuated virulence 2417:2450 The deletion of rgpF resulted in severe ablation of the organism's overall fitness, culminating in significantly attenuated virulence. 28924033 8 107 theme mutant 1368:1373 arg1 strain 1375:1380 The ΔrgpF mutant strain 1358:1380 The ΔrgpF mutant strain 1358:1380 Further, the virulence potential of S. mutans was also drastically reduced following the deletion of rgpF The ΔrgpF mutant strain produced significantly less robust biofilms, indicating an impairment in its ability to adhere to hydroxyapatite surfaces. 28924033 11 108 dep distinct 2054:2061 arg1 While 2013:2017 While 2013:2017 While 2013:2017 While these structures are antigenically distinct to S. mutans, the process by which they are formed and the enzymes leading to their construction are well conserved among streptococci. 28428822 5 0 theme wood 845:848 arg1 mass 837:840 unit mass 832:840 unit mass of wood (dry weight) than wild-type plants 832:883 Without pretreatment, their lignocellulose yielded over 25% more glucose per unit mass of wood (dry weight) than wild-type plants. 28428822 10 1 theme associated 1639:1648 arg1 oligomers 1657:1665 their associated lignin oligomers 1633:1665 their associated lignin oligomers 1633:1665 We propose that deacetylated xylan is partially hydrolyzed in the cell walls, liberating xylo-oligosaccharides and their associated lignin oligomers from the cell wall network. 28428822 10 2 theme deacetylated 1534:1545 arg1 xylan 1547:1551 deacetylated xylan 1534:1551 deacetylated xylan 1534:1551 We propose that deacetylated xylan is partially hydrolyzed in the cell walls, liberating xylo-oligosaccharides and their associated lignin oligomers from the cell wall network. 28428822 7 3 theme molecular 1036:1044 arg1 weight 1046:1051 the molecular weight 1032:1051 the molecular weight of xylan, and xylan-lignin complexes and/or lignin co-extracted with xylan, increased cellulose crystallinity 1032:1161 The results indicate that AnAXE1 expression also reduced the molecular weight of xylan, and xylan-lignin complexes and/or lignin co-extracted with xylan, increased cellulose crystallinity, altered the lignin composition, reducing its syringyl to guaiacyl ratio, and increased lignin solubility in dioxane and hot water. 28428822 3 4 theme xylan 568:572 arg1 AnAXE1 583:588 an acetyl xylan esterase AnAXE1 558:588 an acetyl xylan esterase AnAXE1 from Aspergillus niger 558:611 To optimize lignocellulose for cost-effective saccharification and biofuel production, an acetyl xylan esterase AnAXE1 from Aspergillus niger was introduced into aspen and targeted to cell walls. 28428822 3 5 from niger 607:611 arg1 AnAXE1 583:588 an acetyl xylan esterase AnAXE1 558:588 an acetyl xylan esterase AnAXE1 from Aspergillus niger 558:611 To optimize lignocellulose for cost-effective saccharification and biofuel production, an acetyl xylan esterase AnAXE1 from Aspergillus niger was introduced into aspen and targeted to cell walls. 28428822 7 6 theme increased 1129:1137 arg1 crystallinity 1149:1161 increased cellulose crystallinity 1129:1161 increased cellulose crystallinity 1129:1161 The results indicate that AnAXE1 expression also reduced the molecular weight of xylan, and xylan-lignin complexes and/or lignin co-extracted with xylan, increased cellulose crystallinity, altered the lignin composition, reducing its syringyl to guaiacyl ratio, and increased lignin solubility in dioxane and hot water. 28428822 7 6 theme increased 1129:1137 arg1 xylan 1056:1060 xylan 1056:1060 xylan 1056:1060 The results indicate that AnAXE1 expression also reduced the molecular weight of xylan, and xylan-lignin complexes and/or lignin co-extracted with xylan, increased cellulose crystallinity, altered the lignin composition, reducing its syringyl to guaiacyl ratio, and increased lignin solubility in dioxane and hot water. 28428822 9 7 dep CONCLUSIONS 1417:1427 arg1 revealed 1439:1446 revealed 1439:1446 revealed several changes in plant cell walls caused by deacetylation of xylan 1439:1515 CONCLUSIONS This work revealed several changes in plant cell walls caused by deacetylation of xylan. 28428822 6 8 theme Glucose 886:892 arg1 yields 894:899 Glucose yields 886:899 Glucose yields 886:899 Glucose yields were less improved (+7%) after acid pretreatment, which hydrolyses xylan. 28428822 3 9 theme esterase 574:581 arg1 AnAXE1 583:588 an acetyl xylan esterase AnAXE1 558:588 an acetyl xylan esterase AnAXE1 from Aspergillus niger 558:611 To optimize lignocellulose for cost-effective saccharification and biofuel production, an acetyl xylan esterase AnAXE1 from Aspergillus niger was introduced into aspen and targeted to cell walls. 28428822 9 10 from changes 1456:1462 arg1 walls 1478:1482 plant cell walls 1467:1482 plant cell walls caused by deacetylation of xylan 1467:1515 CONCLUSIONS This work revealed several changes in plant cell walls caused by deacetylation of xylan. 28428822 0 11 theme wood 96:99 arg1 saccharification 70:85 saccharification 70:85 saccharification of aspen wood 70:99 In muro deacetylation of xylan affects lignin properties and improves saccharification of aspen wood. 28428822 2 12 theme hardwood 287:294 arg1 xylan 296:300 hardwood xylan 287:300 hardwood xylan 287:300 However, the extensive acetylation of hardwood xylan hinders lignocellulose saccharification by obstructing enzymatic xylan hydrolysis and causing inhibitory acetic acid concentrations during microbial sugar fermentation. 28428822 1 13 theme BACKGROUND 102:111 arg1 Lignocellulose 113:126 BACKGROUND Lignocellulose 102:126 BACKGROUND Lignocellulose from fast growing hardwood species 102:161 BACKGROUND Lignocellulose from fast growing hardwood species is a preferred source of polysaccharides for advanced biofuels and "green" chemicals. 28428822 1 13 theme BACKGROUND 102:111 arg1 source 178:183 a preferred source 166:183 a preferred source of polysaccharides for advanced biofuels and "green" chemicals 166:246 BACKGROUND Lignocellulose from fast growing hardwood species is a preferred source of polysaccharides for advanced biofuels and "green" chemicals. 28428822 9 14 theme xylan 1511:1515 arg1 deacetylation 1494:1506 deacetylation 1494:1506 deacetylation of xylan 1494:1515 CONCLUSIONS This work revealed several changes in plant cell walls caused by deacetylation of xylan. 28428822 0 15 theme aspen 90:94 arg1 wood 96:99 aspen wood 90:99 aspen wood 90:99 In muro deacetylation of xylan affects lignin properties and improves saccharification of aspen wood. 28428822 4 16 theme reduced 710:716 arg1 acetylation 724:734 reduced xylan acetylation 710:734 reduced xylan acetylation 710:734 RESULTS AnAXE1-expressing plants exhibited reduced xylan acetylation and grew normally. 28428822 7 17 theme lignin 1176:1181 arg1 composition 1183:1193 the lignin composition 1172:1193 the lignin composition 1172:1193 The results indicate that AnAXE1 expression also reduced the molecular weight of xylan, and xylan-lignin complexes and/or lignin co-extracted with xylan, increased cellulose crystallinity, altered the lignin composition, reducing its syringyl to guaiacyl ratio, and increased lignin solubility in dioxane and hot water. 28428822 7 18 theme AnAXE1 1001:1006 arg1 expression 1008:1017 AnAXE1 expression 1001:1017 AnAXE1 expression 1001:1017 The results indicate that AnAXE1 expression also reduced the molecular weight of xylan, and xylan-lignin complexes and/or lignin co-extracted with xylan, increased cellulose crystallinity, altered the lignin composition, reducing its syringyl to guaiacyl ratio, and increased lignin solubility in dioxane and hot water. 28428822 10 19 theme cell 1584:1587 arg1 walls 1589:1593 the cell walls 1580:1593 the cell walls 1580:1593 We propose that deacetylated xylan is partially hydrolyzed in the cell walls, liberating xylo-oligosaccharides and their associated lignin oligomers from the cell wall network. 28428822 11 20 theme xylan 1893:1897 arg1 extractability 1864:1877 the extractability 1860:1877 the extractability of lignin and xylan 1860:1897 Deacetylating xylan thus not only increases its susceptibility to hydrolytic enzymes during saccharification but also changes the cell wall architecture, increasing the extractability of lignin and xylan and facilitating saccharification. 28428822 11 21 theme hydrolytic 1761:1770 arg1 enzymes 1772:1778 hydrolytic enzymes 1761:1778 hydrolytic enzymes 1761:1778 Deacetylating xylan thus not only increases its susceptibility to hydrolytic enzymes during saccharification but also changes the cell wall architecture, increasing the extractability of lignin and xylan and facilitating saccharification. 28428822 1 22 from species 155:161 arg1 Lignocellulose 113:126 BACKGROUND Lignocellulose 102:126 BACKGROUND Lignocellulose from fast growing hardwood species 102:161 BACKGROUND Lignocellulose from fast growing hardwood species is a preferred source of polysaccharides for advanced biofuels and "green" chemicals. 28428822 1 22 from species 155:161 arg1 source 178:183 a preferred source 166:183 a preferred source of polysaccharides for advanced biofuels and "green" chemicals 166:246 BACKGROUND Lignocellulose from fast growing hardwood species is a preferred source of polysaccharides for advanced biofuels and "green" chemicals. 28428822 3 23 theme Aspergillus 595:605 arg1 niger 607:611 Aspergillus niger 595:611 Aspergillus niger 595:611 To optimize lignocellulose for cost-effective saccharification and biofuel production, an acetyl xylan esterase AnAXE1 from Aspergillus niger was introduced into aspen and targeted to cell walls. 28428822 1 24 theme preferred 168:176 arg1 Lignocellulose 113:126 BACKGROUND Lignocellulose 102:126 BACKGROUND Lignocellulose from fast growing hardwood species 102:161 BACKGROUND Lignocellulose from fast growing hardwood species is a preferred source of polysaccharides for advanced biofuels and "green" chemicals. 28428822 1 24 theme preferred 168:176 arg1 source 178:183 a preferred source 166:183 a preferred source of polysaccharides for advanced biofuels and "green" chemicals 166:246 BACKGROUND Lignocellulose from fast growing hardwood species is a preferred source of polysaccharides for advanced biofuels and "green" chemicals. 28428822 5 25 theme unit 832:835 arg1 mass 837:840 unit mass 832:840 unit mass of wood (dry weight) than wild-type plants 832:883 Without pretreatment, their lignocellulose yielded over 25% more glucose per unit mass of wood (dry weight) than wild-type plants. 28428822 6 26 theme acid 932:935 arg1 pretreatment 937:948 acid pretreatment 932:948 acid pretreatment 932:948 Glucose yields were less improved (+7%) after acid pretreatment, which hydrolyses xylan. 28428822 2 27 theme extensive 262:270 arg1 acetylation 272:282 the extensive acetylation 258:282 the extensive acetylation of hardwood xylan 258:300 However, the extensive acetylation of hardwood xylan hinders lignocellulose saccharification by obstructing enzymatic xylan hydrolysis and causing inhibitory acetic acid concentrations during microbial sugar fermentation. 28428822 5 28 theme wild-type 868:876 arg1 plants 878:883 wild-type plants 868:883 wild-type plants 868:883 Without pretreatment, their lignocellulose yielded over 25% more glucose per unit mass of wood (dry weight) than wild-type plants. 28428822 7 29 theme cellulose 1139:1147 arg1 crystallinity 1149:1161 increased cellulose crystallinity 1129:1161 increased cellulose crystallinity 1129:1161 The results indicate that AnAXE1 expression also reduced the molecular weight of xylan, and xylan-lignin complexes and/or lignin co-extracted with xylan, increased cellulose crystallinity, altered the lignin composition, reducing its syringyl to guaiacyl ratio, and increased lignin solubility in dioxane and hot water. 28428822 7 29 theme cellulose 1139:1147 arg1 xylan 1056:1060 xylan 1056:1060 xylan 1056:1060 The results indicate that AnAXE1 expression also reduced the molecular weight of xylan, and xylan-lignin complexes and/or lignin co-extracted with xylan, increased cellulose crystallinity, altered the lignin composition, reducing its syringyl to guaiacyl ratio, and increased lignin solubility in dioxane and hot water. 28428822 7 30 theme co-extracted 1104:1115 arg1 complexes 1080:1088 xylan-lignin complexes 1067:1088 xylan-lignin complexes 1067:1088 The results indicate that AnAXE1 expression also reduced the molecular weight of xylan, and xylan-lignin complexes and/or lignin co-extracted with xylan, increased cellulose crystallinity, altered the lignin composition, reducing its syringyl to guaiacyl ratio, and increased lignin solubility in dioxane and hot water. 28428822 7 30 theme co-extracted 1104:1115 arg1 xylan 1056:1060 xylan 1056:1060 xylan 1056:1060 The results indicate that AnAXE1 expression also reduced the molecular weight of xylan, and xylan-lignin complexes and/or lignin co-extracted with xylan, increased cellulose crystallinity, altered the lignin composition, reducing its syringyl to guaiacyl ratio, and increased lignin solubility in dioxane and hot water. 28428822 2 31 theme acid 414:417 arg1 concentrations 419:432 inhibitory acetic acid concentrations 396:432 inhibitory acetic acid concentrations 396:432 However, the extensive acetylation of hardwood xylan hinders lignocellulose saccharification by obstructing enzymatic xylan hydrolysis and causing inhibitory acetic acid concentrations during microbial sugar fermentation. 28428822 0 32 theme In 0:1 arg1 deacetylation 8:20 In muro deacetylation 0:20 In muro deacetylation of xylan 0:29 In muro deacetylation of xylan affects lignin properties and improves saccharification of aspen wood. 28428822 8 33 theme Lignin-associated 1295:1311 arg1 carbohydrates 1313:1325 Lignin-associated carbohydrates 1295:1325 Lignin-associated carbohydrates 1295:1325 Lignin-associated carbohydrates became enriched in xylose residues, indicating a higher content of xylo-oligosaccharides. 28428822 2 34 theme lignocellulose 310:323 arg1 saccharification 325:340 lignocellulose saccharification 310:340 lignocellulose saccharification 310:340 However, the extensive acetylation of hardwood xylan hinders lignocellulose saccharification by obstructing enzymatic xylan hydrolysis and causing inhibitory acetic acid concentrations during microbial sugar fermentation. 28428822 1 35 theme polysaccharides 188:202 arg1 Lignocellulose 113:126 BACKGROUND Lignocellulose 102:126 BACKGROUND Lignocellulose from fast growing hardwood species 102:161 BACKGROUND Lignocellulose from fast growing hardwood species is a preferred source of polysaccharides for advanced biofuels and "green" chemicals. 28428822 1 35 theme polysaccharides 188:202 arg1 source 178:183 a preferred source 166:183 a preferred source of polysaccharides for advanced biofuels and "green" chemicals 166:246 BACKGROUND Lignocellulose from fast growing hardwood species is a preferred source of polysaccharides for advanced biofuels and "green" chemicals. 28428822 3 36 theme biofuel 538:544 arg1 production 546:555 biofuel production 538:555 biofuel production 538:555 To optimize lignocellulose for cost-effective saccharification and biofuel production, an acetyl xylan esterase AnAXE1 from Aspergillus niger was introduced into aspen and targeted to cell walls. 28428822 8 37 theme higher 1376:1381 arg1 content 1383:1389 a higher content 1374:1389 a higher content of xylo-oligosaccharides 1374:1414 Lignin-associated carbohydrates became enriched in xylose residues, indicating a higher content of xylo-oligosaccharides. 28428822 8 38 theme xylo-oligosaccharides 1394:1414 arg1 content 1383:1389 a higher content 1374:1389 a higher content of xylo-oligosaccharides 1374:1414 Lignin-associated carbohydrates became enriched in xylose residues, indicating a higher content of xylo-oligosaccharides. 28428822 4 39 theme xylan 718:722 arg1 acetylation 724:734 reduced xylan acetylation 710:734 reduced xylan acetylation 710:734 RESULTS AnAXE1-expressing plants exhibited reduced xylan acetylation and grew normally. 28428822 11 40 theme lignin 1882:1887 arg1 extractability 1864:1877 the extractability 1860:1877 the extractability of lignin and xylan 1860:1897 Deacetylating xylan thus not only increases its susceptibility to hydrolytic enzymes during saccharification but also changes the cell wall architecture, increasing the extractability of lignin and xylan and facilitating saccharification. 28428822 6 41 dep improved 911:918 arg1 % 923:923 +7% 921:923 +7% 921:923 Glucose yields were less improved (+7%) after acid pretreatment, which hydrolyses xylan. 28428822 2 42 theme inhibitory 396:405 arg1 concentrations 419:432 inhibitory acetic acid concentrations 396:432 inhibitory acetic acid concentrations 396:432 However, the extensive acetylation of hardwood xylan hinders lignocellulose saccharification by obstructing enzymatic xylan hydrolysis and causing inhibitory acetic acid concentrations during microbial sugar fermentation. 28428822 2 43 theme xylan 296:300 arg1 acetylation 272:282 the extensive acetylation 258:282 the extensive acetylation of hardwood xylan 258:300 However, the extensive acetylation of hardwood xylan hinders lignocellulose saccharification by obstructing enzymatic xylan hydrolysis and causing inhibitory acetic acid concentrations during microbial sugar fermentation. 28428822 1 44 theme advanced 208:215 arg1 biofuels 217:224 advanced biofuels 208:224 advanced biofuels 208:224 BACKGROUND Lignocellulose from fast growing hardwood species is a preferred source of polysaccharides for advanced biofuels and "green" chemicals. 28428822 5 45 theme dry 851:853 arg1 wood 845:848 wood 845:848 wood (dry weight) than wild-type plants 845:883 Without pretreatment, their lignocellulose yielded over 25% more glucose per unit mass of wood (dry weight) than wild-type plants. 28428822 5 45 theme dry 851:853 arg1 weight 855:860 dry weight 851:860 dry weight 851:860 Without pretreatment, their lignocellulose yielded over 25% more glucose per unit mass of wood (dry weight) than wild-type plants. 28428822 3 46 theme acetyl 561:566 arg1 AnAXE1 583:588 an acetyl xylan esterase AnAXE1 558:588 an acetyl xylan esterase AnAXE1 from Aspergillus niger 558:611 To optimize lignocellulose for cost-effective saccharification and biofuel production, an acetyl xylan esterase AnAXE1 from Aspergillus niger was introduced into aspen and targeted to cell walls. 28428822 3 47 theme cost-effective 502:515 arg1 saccharification 517:532 cost-effective saccharification 502:532 cost-effective saccharification 502:532 To optimize lignocellulose for cost-effective saccharification and biofuel production, an acetyl xylan esterase AnAXE1 from Aspergillus niger was introduced into aspen and targeted to cell walls. 28428822 11 48 theme cell 1825:1828 arg1 architecture 1835:1846 the cell wall architecture 1821:1846 the cell wall architecture 1821:1846 Deacetylating xylan thus not only increases its susceptibility to hydrolytic enzymes during saccharification but also changes the cell wall architecture, increasing the extractability of lignin and xylan and facilitating saccharification. 28428822 2 49 theme acetic 407:412 arg1 acid 414:417 acetic acid 407:417 inhibitory acetic acid concentrations 396:432 However, the extensive acetylation of hardwood xylan hinders lignocellulose saccharification by obstructing enzymatic xylan hydrolysis and causing inhibitory acetic acid concentrations during microbial sugar fermentation. 28428822 2 50 theme sugar 451:455 arg1 fermentation 457:468 microbial sugar fermentation 441:468 microbial sugar fermentation 441:468 However, the extensive acetylation of hardwood xylan hinders lignocellulose saccharification by obstructing enzymatic xylan hydrolysis and causing inhibitory acetic acid concentrations during microbial sugar fermentation. 28428822 0 51 theme xylan 25:29 arg1 deacetylation 8:20 In muro deacetylation 0:20 In muro deacetylation of xylan 0:29 In muro deacetylation of xylan affects lignin properties and improves saccharification of aspen wood. 28428822 9 52 theme several 1448:1454 arg1 changes 1456:1462 several changes 1448:1462 several changes in plant cell walls caused by deacetylation of xylan 1448:1515 CONCLUSIONS This work revealed several changes in plant cell walls caused by deacetylation of xylan. 28428822 7 53 theme guaiacyl 1221:1228 arg1 ratio 1230:1234 guaiacyl ratio 1221:1234 guaiacyl ratio 1221:1234 The results indicate that AnAXE1 expression also reduced the molecular weight of xylan, and xylan-lignin complexes and/or lignin co-extracted with xylan, increased cellulose crystallinity, altered the lignin composition, reducing its syringyl to guaiacyl ratio, and increased lignin solubility in dioxane and hot water. 28428822 11 54 theme Deacetylating 1695:1707 arg1 xylan 1709:1713 Deacetylating xylan 1695:1713 Deacetylating xylan 1695:1713 Deacetylating xylan thus not only increases its susceptibility to hydrolytic enzymes during saccharification but also changes the cell wall architecture, increasing the extractability of lignin and xylan and facilitating saccharification. 28428822 2 55 theme microbial 441:449 arg1 fermentation 457:468 microbial sugar fermentation 441:468 microbial sugar fermentation 441:468 However, the extensive acetylation of hardwood xylan hinders lignocellulose saccharification by obstructing enzymatic xylan hydrolysis and causing inhibitory acetic acid concentrations during microbial sugar fermentation. 28428822 5 56 theme more 815:818 arg1 glucose 820:826 over 25% more glucose 806:826 over 25% more glucose 806:826 Without pretreatment, their lignocellulose yielded over 25% more glucose per unit mass of wood (dry weight) than wild-type plants. 28428822 10 57 theme wall 1681:1684 arg1 network 1686:1692 the cell wall network 1672:1692 the cell wall network 1672:1692 We propose that deacetylated xylan is partially hydrolyzed in the cell walls, liberating xylo-oligosaccharides and their associated lignin oligomers from the cell wall network. 28428822 11 58 dep changes 1813:1819 arg1 facilitating 1903:1914 facilitating 1903:1914 facilitating saccharification 1903:1931 Deacetylating xylan thus not only increases its susceptibility to hydrolytic enzymes during saccharification but also changes the cell wall architecture, increasing the extractability of lignin and xylan and facilitating saccharification. 28428822 11 58 dep changes 1813:1819 arg1 increasing 1849:1858 increasing 1849:1858 increasing the extractability of lignin and xylan 1849:1897 Deacetylating xylan thus not only increases its susceptibility to hydrolytic enzymes during saccharification but also changes the cell wall architecture, increasing the extractability of lignin and xylan and facilitating saccharification. 28428822 7 59 theme xylan-lignin 1067:1078 arg1 complexes 1080:1088 xylan-lignin complexes 1067:1088 xylan-lignin complexes 1067:1088 The results indicate that AnAXE1 expression also reduced the molecular weight of xylan, and xylan-lignin complexes and/or lignin co-extracted with xylan, increased cellulose crystallinity, altered the lignin composition, reducing its syringyl to guaiacyl ratio, and increased lignin solubility in dioxane and hot water. 28428822 7 59 theme xylan-lignin 1067:1078 arg1 xylan 1056:1060 xylan 1056:1060 xylan 1056:1060 The results indicate that AnAXE1 expression also reduced the molecular weight of xylan, and xylan-lignin complexes and/or lignin co-extracted with xylan, increased cellulose crystallinity, altered the lignin composition, reducing its syringyl to guaiacyl ratio, and increased lignin solubility in dioxane and hot water. 28428822 2 60 theme xylan 367:371 arg1 hydrolysis 373:382 enzymatic xylan hydrolysis 357:382 enzymatic xylan hydrolysis 357:382 However, the extensive acetylation of hardwood xylan hinders lignocellulose saccharification by obstructing enzymatic xylan hydrolysis and causing inhibitory acetic acid concentrations during microbial sugar fermentation. 28428822 0 61 theme lignin 39:44 arg1 properties 46:55 lignin properties 39:55 lignin properties 39:55 In muro deacetylation of xylan affects lignin properties and improves saccharification of aspen wood. 28428822 7 62 theme lignin 1251:1256 arg1 solubility 1258:1267 lignin solubility 1251:1267 lignin solubility 1251:1267 The results indicate that AnAXE1 expression also reduced the molecular weight of xylan, and xylan-lignin complexes and/or lignin co-extracted with xylan, increased cellulose crystallinity, altered the lignin composition, reducing its syringyl to guaiacyl ratio, and increased lignin solubility in dioxane and hot water. 28428822 3 63 theme cell 655:658 arg1 walls 660:664 cell walls 655:664 cell walls 655:664 To optimize lignocellulose for cost-effective saccharification and biofuel production, an acetyl xylan esterase AnAXE1 from Aspergillus niger was introduced into aspen and targeted to cell walls. 28428822 7 64 theme xylan 1056:1060 arg1 weight 1046:1051 the molecular weight 1032:1051 the molecular weight of xylan, and xylan-lignin complexes and/or lignin co-extracted with xylan, increased cellulose crystallinity 1032:1161 The results indicate that AnAXE1 expression also reduced the molecular weight of xylan, and xylan-lignin complexes and/or lignin co-extracted with xylan, increased cellulose crystallinity, altered the lignin composition, reducing its syringyl to guaiacyl ratio, and increased lignin solubility in dioxane and hot water. 28428822 2 65 theme enzymatic 357:365 arg1 hydrolysis 373:382 enzymatic xylan hydrolysis 357:382 enzymatic xylan hydrolysis 357:382 However, the extensive acetylation of hardwood xylan hinders lignocellulose saccharification by obstructing enzymatic xylan hydrolysis and causing inhibitory acetic acid concentrations during microbial sugar fermentation. 28428822 9 66 theme plant 1467:1471 arg1 walls 1478:1482 plant cell walls 1467:1482 plant cell walls caused by deacetylation of xylan 1467:1515 CONCLUSIONS This work revealed several changes in plant cell walls caused by deacetylation of xylan. 28428822 1 67 theme fast 133:136 arg1 species 155:161 fast growing hardwood species 133:161 fast growing hardwood species 133:161 BACKGROUND Lignocellulose from fast growing hardwood species is a preferred source of polysaccharides for advanced biofuels and "green" chemicals. 28428822 4 68 theme AnAXE1-expressing 675:691 arg1 plants 693:698 RESULTS AnAXE1-expressing plants 667:698 RESULTS AnAXE1-expressing plants 667:698 RESULTS AnAXE1-expressing plants exhibited reduced xylan acetylation and grew normally. 28428822 11 69 theme wall 1830:1833 arg1 architecture 1835:1846 the cell wall architecture 1821:1846 the cell wall architecture 1821:1846 Deacetylating xylan thus not only increases its susceptibility to hydrolytic enzymes during saccharification but also changes the cell wall architecture, increasing the extractability of lignin and xylan and facilitating saccharification. 28428822 7 70 with co-extracted 1104:1115 arg1 xylan 1122:1126 xylan 1122:1126 xylan 1122:1126 The results indicate that AnAXE1 expression also reduced the molecular weight of xylan, and xylan-lignin complexes and/or lignin co-extracted with xylan, increased cellulose crystallinity, altered the lignin composition, reducing its syringyl to guaiacyl ratio, and increased lignin solubility in dioxane and hot water. 28428822 1 71 theme growing 138:144 arg1 species 155:161 fast growing hardwood species 133:161 fast growing hardwood species 133:161 BACKGROUND Lignocellulose from fast growing hardwood species is a preferred source of polysaccharides for advanced biofuels and "green" chemicals. 28428822 4 72 theme RESULTS 667:673 arg1 plants 693:698 RESULTS AnAXE1-expressing plants 667:698 RESULTS AnAXE1-expressing plants 667:698 RESULTS AnAXE1-expressing plants exhibited reduced xylan acetylation and grew normally. 28428822 7 73 theme hot 1284:1286 arg1 water 1288:1292 hot water 1284:1292 hot water 1284:1292 The results indicate that AnAXE1 expression also reduced the molecular weight of xylan, and xylan-lignin complexes and/or lignin co-extracted with xylan, increased cellulose crystallinity, altered the lignin composition, reducing its syringyl to guaiacyl ratio, and increased lignin solubility in dioxane and hot water. 28428822 8 74 theme xylose 1346:1351 arg1 residues 1353:1360 xylose residues 1346:1360 xylose residues 1346:1360 Lignin-associated carbohydrates became enriched in xylose residues, indicating a higher content of xylo-oligosaccharides. 28428822 1 75 theme hardwood 146:153 arg1 species 155:161 fast growing hardwood species 133:161 fast growing hardwood species 133:161 BACKGROUND Lignocellulose from fast growing hardwood species is a preferred source of polysaccharides for advanced biofuels and "green" chemicals. 28428822 1 76 theme " 236:236 arg1 chemicals 238:246 "green" chemicals 230:246 "green" chemicals 230:246 BACKGROUND Lignocellulose from fast growing hardwood species is a preferred source of polysaccharides for advanced biofuels and "green" chemicals. 28428822 10 77 theme lignin 1650:1655 arg1 oligomers 1657:1665 their associated lignin oligomers 1633:1665 their associated lignin oligomers 1633:1665 We propose that deacetylated xylan is partially hydrolyzed in the cell walls, liberating xylo-oligosaccharides and their associated lignin oligomers from the cell wall network. 28428822 0 78 dep In 0:1 arg1 muro 3:6 muro 3:6 muro 3:6 In muro deacetylation of xylan affects lignin properties and improves saccharification of aspen wood. 28428822 9 79 theme cell 1473:1476 arg1 walls 1478:1482 plant cell walls 1467:1482 plant cell walls caused by deacetylation of xylan 1467:1515 CONCLUSIONS This work revealed several changes in plant cell walls caused by deacetylation of xylan. 28428822 10 80 theme cell 1676:1679 arg1 network 1686:1692 the cell wall network 1672:1692 the cell wall network 1672:1692 We propose that deacetylated xylan is partially hydrolyzed in the cell walls, liberating xylo-oligosaccharides and their associated lignin oligomers from the cell wall network. 24860115 14 0 theme novel 1831:1835 arg1 species 1837:1843 a novel species 1829:1843 a novel species 1829:1843 Based on its phenotypic characteristics and phylogenetic traits, strain MO-SPC1(T) is placed in a separate taxon at the level of a novel species within the genus Spirochaeta, for which the name Spirochaeta psychrophila sp. 24860115 5 1 from pH 657:658 arg1 pH 632:633 pH 6.0-7.5 632:641 pH 6.0-7.5 (optimally at pH 6.8-7.0) 632:667 Strain MO-SPC1(T) grew at 0-18 °C (optimally at 15 °C), at pH 6.0-7.5 (optimally at pH 6.8-7.0) and in 20-70 g NaCl l(-1) (optimally at 30-40 NaCl l(-1)). 24860115 8 2 theme unknown 1031:1037 arg1 lipid 1039:1043 an unknown lipid 1028:1043 an unknown lipid 1028:1043 The abundant polar lipids of strain MO-SPC1(T) were diphosphatidylglycerol, phosphatidylglycerol, unknown phospholipids and an unknown lipid. 24860115 7 3 theme end 815:817 arg1 acetate 857:863 acetate 857:863 acetate 857:863 The major end products of glucose fermentation were acetate, ethanol, hydrogen and carbon dioxide. 24860115 7 3 theme end 815:817 arg1 products 819:826 The major end products 805:826 The major end products of glucose fermentation 805:850 The major end products of glucose fermentation were acetate, ethanol, hydrogen and carbon dioxide. 24860115 9 4 theme cellular 1056:1063 arg1 C 1101:1101 C(14 : 0) 1101:1109 C(14 : 0) 1101:1109 The major cellular fatty acids (>5% of the total) were C(14 : 0), C(16 : 0), iso-C(13 : 0), iso-C(14 : 0), iso-C(15 : 0), anteiso-C(13 : 0) and anteiso-C(15 : 0). 24860115 9 4 theme cellular 1056:1063 arg1 acids 1071:1075 The major cellular fatty acids 1046:1075 The major cellular fatty acids (>5% of the total) 1046:1094 The major cellular fatty acids (>5% of the total) were C(14 : 0), C(16 : 0), iso-C(13 : 0), iso-C(14 : 0), iso-C(15 : 0), anteiso-C(13 : 0) and anteiso-C(15 : 0). 24860115 13 5 theme Spirochaeta 1663:1673 arg1 R1 1685:1686 Spirochaeta litoralis R1 1663:1686 Spirochaeta litoralis R1(T) (89.4%) 1663:1697 16S rRNA gene sequence-based phylogenetic analysis showed that strain MO-SPC1(T) was affiliated with the genus Spirochaeta, and its closest relatives were Spirochaeta isovalerica MA-2(T) (95.6% sequence identity) and Spirochaeta litoralis R1(T) (89.4%). 24860115 13 5 theme Spirochaeta 1663:1673 arg1 % 1696:1696 89.4% 1692:1696 89.4% 1692:1696 16S rRNA gene sequence-based phylogenetic analysis showed that strain MO-SPC1(T) was affiliated with the genus Spirochaeta, and its closest relatives were Spirochaeta isovalerica MA-2(T) (95.6% sequence identity) and Spirochaeta litoralis R1(T) (89.4%). 24860115 13 5 theme Spirochaeta 1663:1673 arg1 T 1688:1688 T 1688:1688 T 1688:1688 16S rRNA gene sequence-based phylogenetic analysis showed that strain MO-SPC1(T) was affiliated with the genus Spirochaeta, and its closest relatives were Spirochaeta isovalerica MA-2(T) (95.6% sequence identity) and Spirochaeta litoralis R1(T) (89.4%). 24860115 14 6 theme Spirochaeta 1894:1904 arg1 sp 1919:1920 the name Spirochaeta psychrophila sp 1885:1920 the name Spirochaeta psychrophila sp 1885:1920 Based on its phenotypic characteristics and phylogenetic traits, strain MO-SPC1(T) is placed in a separate taxon at the level of a novel species within the genus Spirochaeta, for which the name Spirochaeta psychrophila sp. 24860115 17 7 theme first 2081:2085 arg1 report 2087:2092 the first report 2077:2092 the first report of an isolate of the phylum Spirochaetes from a deep-sea sedimentary environment, and of an obligately psychrophilic nature 2077:2216 To our knowledge, this is the first report of an isolate of the phylum Spirochaetes from a deep-sea sedimentary environment, and of an obligately psychrophilic nature. 24860115 17 7 theme first 2081:2085 arg1 this 2069:2072 this 2069:2072 this 2069:2072 To our knowledge, this is the first report of an isolate of the phylum Spirochaetes from a deep-sea sedimentary environment, and of an obligately psychrophilic nature. 24860115 13 8 theme sequence-based 1460:1473 arg1 analysis 1488:1495 16S rRNA gene sequence-based phylogenetic analysis 1446:1495 16S rRNA gene sequence-based phylogenetic analysis 1446:1495 16S rRNA gene sequence-based phylogenetic analysis showed that strain MO-SPC1(T) was affiliated with the genus Spirochaeta, and its closest relatives were Spirochaeta isovalerica MA-2(T) (95.6% sequence identity) and Spirochaeta litoralis R1(T) (89.4%). 24860115 2 9 theme microbial 253:261 arg1 community 263:271 a methanogenic microbial community 238:271 a methanogenic microbial community grown in a continuous-flow bioreactor 238:309 An obligately anaerobic, psychrophilic spirochaete, strain MO-SPC1(T), was isolated from a methanogenic microbial community grown in a continuous-flow bioreactor. 24860115 1 10 attach isolated 63:70 arg2 spirochaete 51:61 a psychrophilic spirochaete 35:61 a psychrophilic spirochaete isolated from subseafloor sediment 35:96 nov., a psychrophilic spirochaete isolated from subseafloor sediment, and emended description of the genus Spirochaeta. 24860115 1 10 attach isolated 63:70 arg1 sediment 89:96 subseafloor sediment 77:96 subseafloor sediment 77:96 nov., a psychrophilic spirochaete isolated from subseafloor sediment, and emended description of the genus Spirochaeta. 24860115 16 11 theme 17280 2025:2029 arg1 T 2046:2046 T 2046:2046 T 2046:2046 The type strain is MO-SPC1(T) ( = JCM 17280(T) = DSM 23951(T)). 24860115 16 11 theme 17280 2025:2029 arg1 23951 2040:2044  = JCM 17280(T) = DSM 23951 2018:2044  = JCM 17280(T) = DSM 23951(T) 2018:2047 The type strain is MO-SPC1(T) ( = JCM 17280(T) = DSM 23951(T)). 24860115 10 12 theme first 1251:1255 arg1 this 1239:1242 this 1239:1242 this 1239:1242 To the best of our knowledge, this is the first report of the fatty acids iso-C(13 : 0) and anteiso-C(13 : 0) from a species of the genus Spirochaeta. 24860115 10 12 theme first 1251:1255 arg1 report 1257:1262 the first report 1247:1262 the first report of the fatty acids iso-C(13 : 0) and anteiso-C(13 : 0) from a species of the genus Spirochaeta 1247:1357 To the best of our knowledge, this is the first report of the fatty acids iso-C(13 : 0) and anteiso-C(13 : 0) from a species of the genus Spirochaeta. 24860115 9 13 theme total 1089:1093 arg1 total 1089:1093 total 1089:1093 total 1089:1093 The major cellular fatty acids (>5% of the total) were C(14 : 0), C(16 : 0), iso-C(13 : 0), iso-C(14 : 0), iso-C(15 : 0), anteiso-C(13 : 0) and anteiso-C(15 : 0). 24860115 9 13 theme total 1089:1093 arg1 % 1080:1080 >5% 1078:1080 >5% 1078:1080 The major cellular fatty acids (>5% of the total) were C(14 : 0), C(16 : 0), iso-C(13 : 0), iso-C(14 : 0), iso-C(15 : 0), anteiso-C(13 : 0) and anteiso-C(15 : 0). 24860115 16 14 theme T 2031:2031 arg1 T 2046:2046 T 2046:2046 T 2046:2046 The type strain is MO-SPC1(T) ( = JCM 17280(T) = DSM 23951(T)). 24860115 16 14 theme T 2031:2031 arg1 23951 2040:2044  = JCM 17280(T) = DSM 23951 2018:2044  = JCM 17280(T) = DSM 23951(T) 2018:2047 The type strain is MO-SPC1(T) ( = JCM 17280(T) = DSM 23951(T)). 24860115 10 15 theme genus 1341:1345 arg1 Spirochaeta 1347:1357 the genus Spirochaeta 1337:1357 the genus Spirochaeta 1337:1357 To the best of our knowledge, this is the first report of the fatty acids iso-C(13 : 0) and anteiso-C(13 : 0) from a species of the genus Spirochaeta. 24860115 16 16 theme  = DSM 2033:2038 arg1 T 2046:2046 T 2046:2046 T 2046:2046 The type strain is MO-SPC1(T) ( = JCM 17280(T) = DSM 23951(T)). 24860115 16 16 theme  = DSM 2033:2038 arg1 23951 2040:2044  = JCM 17280(T) = DSM 23951 2018:2044  = JCM 17280(T) = DSM 23951(T) 2018:2047 The type strain is MO-SPC1(T) ( = JCM 17280(T) = DSM 23951(T)). 24860115 9 17 theme major 1050:1054 arg1 C 1101:1101 C(14 : 0) 1101:1109 C(14 : 0) 1101:1109 The major cellular fatty acids (>5% of the total) were C(14 : 0), C(16 : 0), iso-C(13 : 0), iso-C(14 : 0), iso-C(15 : 0), anteiso-C(13 : 0) and anteiso-C(15 : 0). 24860115 9 17 theme major 1050:1054 arg1 acids 1071:1075 The major cellular fatty acids 1046:1075 The major cellular fatty acids (>5% of the total) 1046:1094 The major cellular fatty acids (>5% of the total) were C(14 : 0), C(16 : 0), iso-C(13 : 0), iso-C(14 : 0), iso-C(15 : 0), anteiso-C(13 : 0) and anteiso-C(15 : 0). 24860115 13 18 theme 16S 1446:1448 arg1 analysis 1488:1495 16S rRNA gene sequence-based phylogenetic analysis 1446:1495 16S rRNA gene sequence-based phylogenetic analysis 1446:1495 16S rRNA gene sequence-based phylogenetic analysis showed that strain MO-SPC1(T) was affiliated with the genus Spirochaeta, and its closest relatives were Spirochaeta isovalerica MA-2(T) (95.6% sequence identity) and Spirochaeta litoralis R1(T) (89.4%). 24860115 1 19 theme genus 130:134 arg1 Spirochaeta 136:146 the genus Spirochaeta 126:146 the genus Spirochaeta 126:146 nov., a psychrophilic spirochaete isolated from subseafloor sediment, and emended description of the genus Spirochaeta. 24860115 17 20 theme sedimentary 2151:2161 arg1 environment 2163:2173 a deep-sea sedimentary environment 2140:2173 a deep-sea sedimentary environment 2140:2173 To our knowledge, this is the first report of an isolate of the phylum Spirochaetes from a deep-sea sedimentary environment, and of an obligately psychrophilic nature. 24860115 13 21 theme gene 1455:1458 arg1 analysis 1488:1495 16S rRNA gene sequence-based phylogenetic analysis 1446:1495 16S rRNA gene sequence-based phylogenetic analysis 1446:1495 16S rRNA gene sequence-based phylogenetic analysis showed that strain MO-SPC1(T) was affiliated with the genus Spirochaeta, and its closest relatives were Spirochaeta isovalerica MA-2(T) (95.6% sequence identity) and Spirochaeta litoralis R1(T) (89.4%). 24860115 5 22 theme g 682:682 arg1 l 720:720 optimally at 30-40 NaCl l(-1) 696:724 optimally at 30-40 NaCl l(-1) 696:724 Strain MO-SPC1(T) grew at 0-18 °C (optimally at 15 °C), at pH 6.0-7.5 (optimally at pH 6.8-7.0) and in 20-70 g NaCl l(-1) (optimally at 30-40 NaCl l(-1)). 24860115 5 22 theme g 682:682 arg1 -1 691:692 -1 691:692 -1 691:692 Strain MO-SPC1(T) grew at 0-18 °C (optimally at 15 °C), at pH 6.0-7.5 (optimally at pH 6.8-7.0) and in 20-70 g NaCl l(-1) (optimally at 30-40 NaCl l(-1)). 24860115 5 22 theme g 682:682 arg1 l 689:689 20-70 g NaCl l 676:689 20-70 g NaCl l(-1) (optimally at 30-40 NaCl l(-1)) 676:725 Strain MO-SPC1(T) grew at 0-18 °C (optimally at 15 °C), at pH 6.0-7.5 (optimally at pH 6.8-7.0) and in 20-70 g NaCl l(-1) (optimally at 30-40 NaCl l(-1)). 24860115 3 23 from Peninsula 397:405 arg1 Ocean 445:449 the north-western Pacific Ocean 419:449 the north-western Pacific Ocean 419:449 Originally, this community was obtained from subseafloor sediments off the Shimokita Peninsula of Japan in the north-western Pacific Ocean. 24860115 10 24 from species 1326:1332 arg1 this 1239:1242 this 1239:1242 this 1239:1242 To the best of our knowledge, this is the first report of the fatty acids iso-C(13 : 0) and anteiso-C(13 : 0) from a species of the genus Spirochaeta. 24860115 10 24 from species 1326:1332 arg1 report 1257:1262 the first report 1247:1262 the first report of the fatty acids iso-C(13 : 0) and anteiso-C(13 : 0) from a species of the genus Spirochaeta 1247:1357 To the best of our knowledge, this is the first report of the fatty acids iso-C(13 : 0) and anteiso-C(13 : 0) from a species of the genus Spirochaeta. 24860115 13 25 theme Spirochaeta 1601:1611 arg1 T 1630:1630 T 1630:1630 T 1630:1630 16S rRNA gene sequence-based phylogenetic analysis showed that strain MO-SPC1(T) was affiliated with the genus Spirochaeta, and its closest relatives were Spirochaeta isovalerica MA-2(T) (95.6% sequence identity) and Spirochaeta litoralis R1(T) (89.4%). 24860115 13 25 theme Spirochaeta 1601:1611 arg1 MA-2 1625:1628 Spirochaeta isovalerica MA-2 1601:1628 Spirochaeta isovalerica MA-2(T) (95.6% sequence identity) 1601:1657 16S rRNA gene sequence-based phylogenetic analysis showed that strain MO-SPC1(T) was affiliated with the genus Spirochaeta, and its closest relatives were Spirochaeta isovalerica MA-2(T) (95.6% sequence identity) and Spirochaeta litoralis R1(T) (89.4%). 24860115 13 25 theme Spirochaeta 1601:1611 arg1 identity 1649:1656 95.6% sequence identity 1634:1656 95.6% sequence identity 1634:1656 16S rRNA gene sequence-based phylogenetic analysis showed that strain MO-SPC1(T) was affiliated with the genus Spirochaeta, and its closest relatives were Spirochaeta isovalerica MA-2(T) (95.6% sequence identity) and Spirochaeta litoralis R1(T) (89.4%). 24860115 7 26 theme glucose 831:837 arg1 fermentation 839:850 glucose fermentation 831:850 glucose fermentation 831:850 The major end products of glucose fermentation were acetate, ethanol, hydrogen and carbon dioxide. 24860115 9 27 dep acids 1071:1075 arg1 total 1089:1093 total 1089:1093 total 1089:1093 The major cellular fatty acids (>5% of the total) were C(14 : 0), C(16 : 0), iso-C(13 : 0), iso-C(14 : 0), iso-C(15 : 0), anteiso-C(13 : 0) and anteiso-C(15 : 0). 24860115 9 27 dep acids 1071:1075 arg1 % 1080:1080 >5% 1078:1080 >5% 1078:1080 The major cellular fatty acids (>5% of the total) were C(14 : 0), C(16 : 0), iso-C(13 : 0), iso-C(14 : 0), iso-C(15 : 0), anteiso-C(13 : 0) and anteiso-C(15 : 0). 24860115 4 28 theme 0.25-0.55×3.6-15 505:520 arg1 cells 456:460 The cells 452:460 The cells 452:460 The cells were motile, Gram-stain-negative, helical, 0.25-0.55×3.6-15 µm, with a wavelength of approximately 0.5-0.6 µm. 24860115 4 28 theme 0.25-0.55×3.6-15 505:520 arg1 µm 522:523 motile, Gram-stain-negative, helical, 0.25-0.55×3.6-15 µm 467:523 motile, Gram-stain-negative, helical, 0.25-0.55×3.6-15 µm 467:523 The cells were motile, Gram-stain-negative, helical, 0.25-0.55×3.6-15 µm, with a wavelength of approximately 0.5-0.6 µm. 24860115 15 29 theme true 1956:1959 arg1 physiology 1975:1984 its true psychrophilic physiology 1952:1984 its true psychrophilic physiology 1952:1984 nov. is proposed, reflecting its true psychrophilic physiology. 24860115 4 30 theme motile 467:472 arg1 cells 456:460 The cells 452:460 The cells 452:460 The cells were motile, Gram-stain-negative, helical, 0.25-0.55×3.6-15 µm, with a wavelength of approximately 0.5-0.6 µm. 24860115 4 30 theme motile 467:472 arg1 µm 522:523 motile, Gram-stain-negative, helical, 0.25-0.55×3.6-15 µm 467:523 motile, Gram-stain-negative, helical, 0.25-0.55×3.6-15 µm 467:523 The cells were motile, Gram-stain-negative, helical, 0.25-0.55×3.6-15 µm, with a wavelength of approximately 0.5-0.6 µm. 24860115 3 31 dep Peninsula 397:405 arg1 off 379:381 off 379:381 off 379:381 Originally, this community was obtained from subseafloor sediments off the Shimokita Peninsula of Japan in the north-western Pacific Ocean. 24860115 3 32 theme Pacific 437:443 arg1 Ocean 445:449 the north-western Pacific Ocean 419:449 the north-western Pacific Ocean 419:449 Originally, this community was obtained from subseafloor sediments off the Shimokita Peninsula of Japan in the north-western Pacific Ocean. 24860115 8 33 theme polar 917:921 arg1 lipids 923:928 The abundant polar lipids 904:928 The abundant polar lipids of strain MO-SPC1(T) 904:949 The abundant polar lipids of strain MO-SPC1(T) were diphosphatidylglycerol, phosphatidylglycerol, unknown phospholipids and an unknown lipid. 24860115 8 33 theme polar 917:921 arg1 diphosphatidylglycerol 956:977 diphosphatidylglycerol 956:977 diphosphatidylglycerol 956:977 The abundant polar lipids of strain MO-SPC1(T) were diphosphatidylglycerol, phosphatidylglycerol, unknown phospholipids and an unknown lipid. 24860115 7 34 theme major 809:813 arg1 acetate 857:863 acetate 857:863 acetate 857:863 The major end products of glucose fermentation were acetate, ethanol, hydrogen and carbon dioxide. 24860115 7 34 theme major 809:813 arg1 products 819:826 The major end products 805:826 The major end products of glucose fermentation 805:850 The major end products of glucose fermentation were acetate, ethanol, hydrogen and carbon dioxide. 24860115 1 35 theme subseafloor 77:87 arg1 sediment 89:96 subseafloor sediment 77:96 subseafloor sediment 77:96 nov., a psychrophilic spirochaete isolated from subseafloor sediment, and emended description of the genus Spirochaeta. 24860115 5 36 dep °C 624:625 arg1 optimally 608:616 optimally 608:616 optimally 608:616 Strain MO-SPC1(T) grew at 0-18 °C (optimally at 15 °C), at pH 6.0-7.5 (optimally at pH 6.8-7.0) and in 20-70 g NaCl l(-1) (optimally at 30-40 NaCl l(-1)). 24860115 14 37 theme phylogenetic 1744:1755 arg1 traits 1757:1762 phylogenetic traits 1744:1762 phylogenetic traits 1744:1762 Based on its phenotypic characteristics and phylogenetic traits, strain MO-SPC1(T) is placed in a separate taxon at the level of a novel species within the genus Spirochaeta, for which the name Spirochaeta psychrophila sp. 24860115 0 38 theme Spirochaeta 0:10 arg1 sp 25:26 Spirochaeta psychrophila sp 0:26 Spirochaeta psychrophila sp. 0:27 Spirochaeta psychrophila sp. 24860115 12 39 theme mol 1440:1442 arg1 % 1443:1443 39.8 mol% 1435:1443 39.8 mol% 1435:1443 The G+C content of the genomic DNA was 39.8 mol%. 24860115 12 39 theme mol 1440:1442 arg1 content 1404:1410 The G+C content 1396:1410 The G+C content of the genomic DNA 1396:1429 The G+C content of the genomic DNA was 39.8 mol%. 24860115 5 40 theme NaCl 715:718 arg1 l 720:720 optimally at 30-40 NaCl l(-1) 696:724 optimally at 30-40 NaCl l(-1) 696:724 Strain MO-SPC1(T) grew at 0-18 °C (optimally at 15 °C), at pH 6.0-7.5 (optimally at pH 6.8-7.0) and in 20-70 g NaCl l(-1) (optimally at 30-40 NaCl l(-1)). 24860115 5 40 theme NaCl 715:718 arg1 l 689:689 20-70 g NaCl l 676:689 20-70 g NaCl l(-1) (optimally at 30-40 NaCl l(-1)) 676:725 Strain MO-SPC1(T) grew at 0-18 °C (optimally at 15 °C), at pH 6.0-7.5 (optimally at pH 6.8-7.0) and in 20-70 g NaCl l(-1) (optimally at 30-40 NaCl l(-1)). 24860115 8 41 theme MO-SPC1 940:946 arg1 lipids 923:928 The abundant polar lipids 904:928 The abundant polar lipids of strain MO-SPC1(T) 904:949 The abundant polar lipids of strain MO-SPC1(T) were diphosphatidylglycerol, phosphatidylglycerol, unknown phospholipids and an unknown lipid. 24860115 8 41 theme MO-SPC1 940:946 arg1 diphosphatidylglycerol 956:977 diphosphatidylglycerol 956:977 diphosphatidylglycerol 956:977 The abundant polar lipids of strain MO-SPC1(T) were diphosphatidylglycerol, phosphatidylglycerol, unknown phospholipids and an unknown lipid. 24860115 1 42 theme emended 103:109 arg1 description 111:121 emended description 103:121 emended description of the genus Spirochaeta 103:146 nov., a psychrophilic spirochaete isolated from subseafloor sediment, and emended description of the genus Spirochaeta. 24860115 3 43 theme Japan 410:414 arg1 Peninsula 397:405 the Shimokita Peninsula 383:405 the Shimokita Peninsula of Japan in the north-western Pacific Ocean 383:449 Originally, this community was obtained from subseafloor sediments off the Shimokita Peninsula of Japan in the north-western Pacific Ocean. 24860115 2 44 theme psychrophilic 174:186 arg1 spirochaete 188:198 An obligately anaerobic, psychrophilic spirochaete 149:198 spirochaete 188:198 An obligately anaerobic, psychrophilic spirochaete, strain MO-SPC1(T), was isolated from a methanogenic microbial community grown in a continuous-flow bioreactor. 24860115 2 44 theme psychrophilic 174:186 arg1 MO-SPC1 208:214 strain MO-SPC1 201:214 strain MO-SPC1(T) 201:217 An obligately anaerobic, psychrophilic spirochaete, strain MO-SPC1(T), was isolated from a methanogenic microbial community grown in a continuous-flow bioreactor. 24860115 10 45 dep acids 1277:1281 arg1  0 1293:1294  0 1293:1294  0 1293:1294 To the best of our knowledge, this is the first report of the fatty acids iso-C(13 : 0) and anteiso-C(13 : 0) from a species of the genus Spirochaeta. 24860115 10 45 dep acids 1277:1281 arg1 anteiso-C 1301:1309 anteiso-C 1301:1309 anteiso-C 1301:1309 To the best of our knowledge, this is the first report of the fatty acids iso-C(13 : 0) and anteiso-C(13 : 0) from a species of the genus Spirochaeta. 24860115 10 45 dep acids 1277:1281 arg1 iso-C 1283:1287 iso-C 1283:1287 iso-C 1283:1287 To the best of our knowledge, this is the first report of the fatty acids iso-C(13 : 0) and anteiso-C(13 : 0) from a species of the genus Spirochaeta. 24860115 10 45 dep acids 1277:1281 arg1  0 1315:1316  0 1315:1316  0 1315:1316 To the best of our knowledge, this is the first report of the fatty acids iso-C(13 : 0) and anteiso-C(13 : 0) from a species of the genus Spirochaeta. 24860115 10 45 dep acids 1277:1281 arg1 acids 1277:1281 the fatty acids iso-C(13 : 0) and anteiso-C(13 : 0) 1267:1317 the fatty acids iso-C(13 : 0) and anteiso-C(13 : 0) 1267:1317 To the best of our knowledge, this is the first report of the fatty acids iso-C(13 : 0) and anteiso-C(13 : 0) from a species of the genus Spirochaeta. 24860115 10 46 theme acids 1277:1281 arg1 this 1239:1242 this 1239:1242 this 1239:1242 To the best of our knowledge, this is the first report of the fatty acids iso-C(13 : 0) and anteiso-C(13 : 0) from a species of the genus Spirochaeta. 24860115 10 46 theme acids 1277:1281 arg1 report 1257:1262 the first report 1247:1262 the first report of the fatty acids iso-C(13 : 0) and anteiso-C(13 : 0) from a species of the genus Spirochaeta 1247:1357 To the best of our knowledge, this is the first report of the fatty acids iso-C(13 : 0) and anteiso-C(13 : 0) from a species of the genus Spirochaeta. 24860115 5 47 from °C 624:625 arg1 °C 604:605 0-18 °C 599:605 0-18 °C (optimally at 15 °C) 599:626 Strain MO-SPC1(T) grew at 0-18 °C (optimally at 15 °C), at pH 6.0-7.5 (optimally at pH 6.8-7.0) and in 20-70 g NaCl l(-1) (optimally at 30-40 NaCl l(-1)). 24860115 12 48 theme genomic 1419:1425 arg1 DNA 1427:1429 the genomic DNA 1415:1429 the genomic DNA 1415:1429 The G+C content of the genomic DNA was 39.8 mol%. 24860115 2 49 theme anaerobic 163:171 arg1 spirochaete 188:198 An obligately anaerobic, psychrophilic spirochaete 149:198 spirochaete 188:198 An obligately anaerobic, psychrophilic spirochaete, strain MO-SPC1(T), was isolated from a methanogenic microbial community grown in a continuous-flow bioreactor. 24860115 2 49 theme anaerobic 163:171 arg1 MO-SPC1 208:214 strain MO-SPC1 201:214 strain MO-SPC1(T) 201:217 An obligately anaerobic, psychrophilic spirochaete, strain MO-SPC1(T), was isolated from a methanogenic microbial community grown in a continuous-flow bioreactor. 24860115 17 50 from isolate 2100:2106 arg1 environment 2163:2173 a deep-sea sedimentary environment 2140:2173 a deep-sea sedimentary environment 2140:2173 To our knowledge, this is the first report of an isolate of the phylum Spirochaetes from a deep-sea sedimentary environment, and of an obligately psychrophilic nature. 24860115 4 51 with µm 522:523 arg1 wavelength 533:542 a wavelength 531:542 a wavelength of approximately 0.5-0.6 µm 531:570 The cells were motile, Gram-stain-negative, helical, 0.25-0.55×3.6-15 µm, with a wavelength of approximately 0.5-0.6 µm. 24860115 13 52 theme litoralis 1675:1683 arg1 R1 1685:1686 Spirochaeta litoralis R1 1663:1686 Spirochaeta litoralis R1(T) (89.4%) 1663:1697 16S rRNA gene sequence-based phylogenetic analysis showed that strain MO-SPC1(T) was affiliated with the genus Spirochaeta, and its closest relatives were Spirochaeta isovalerica MA-2(T) (95.6% sequence identity) and Spirochaeta litoralis R1(T) (89.4%). 24860115 13 52 theme litoralis 1675:1683 arg1 % 1696:1696 89.4% 1692:1696 89.4% 1692:1696 16S rRNA gene sequence-based phylogenetic analysis showed that strain MO-SPC1(T) was affiliated with the genus Spirochaeta, and its closest relatives were Spirochaeta isovalerica MA-2(T) (95.6% sequence identity) and Spirochaeta litoralis R1(T) (89.4%). 24860115 13 52 theme litoralis 1675:1683 arg1 T 1688:1688 T 1688:1688 T 1688:1688 16S rRNA gene sequence-based phylogenetic analysis showed that strain MO-SPC1(T) was affiliated with the genus Spirochaeta, and its closest relatives were Spirochaeta isovalerica MA-2(T) (95.6% sequence identity) and Spirochaeta litoralis R1(T) (89.4%). 24860115 12 53 theme G+C 1400:1402 arg1 % 1443:1443 39.8 mol% 1435:1443 39.8 mol% 1435:1443 The G+C content of the genomic DNA was 39.8 mol%. 24860115 12 53 theme G+C 1400:1402 arg1 content 1404:1410 The G+C content 1396:1410 The G+C content of the genomic DNA 1396:1429 The G+C content of the genomic DNA was 39.8 mol%. 24860115 1 54 theme psychrophilic 37:49 arg1 spirochaete 51:61 a psychrophilic spirochaete 35:61 a psychrophilic spirochaete isolated from subseafloor sediment 35:96 nov., a psychrophilic spirochaete isolated from subseafloor sediment, and emended description of the genus Spirochaeta. 24860115 14 55 theme species 1837:1843 arg1 level 1820:1824 the level 1816:1824 the level of a novel species within the genus Spirochaeta, for which the name Spirochaeta psychrophila sp 1816:1920 Based on its phenotypic characteristics and phylogenetic traits, strain MO-SPC1(T) is placed in a separate taxon at the level of a novel species within the genus Spirochaeta, for which the name Spirochaeta psychrophila sp. 24860115 17 56 theme Spirochaetes 2122:2133 arg1 isolate 2100:2106 an isolate 2097:2106 an isolate of the phylum Spirochaetes from a deep-sea sedimentary environment 2097:2173 To our knowledge, this is the first report of an isolate of the phylum Spirochaetes from a deep-sea sedimentary environment, and of an obligately psychrophilic nature. 24860115 13 57 theme strain 1509:1514 arg1 T 1524:1524 T 1524:1524 T 1524:1524 16S rRNA gene sequence-based phylogenetic analysis showed that strain MO-SPC1(T) was affiliated with the genus Spirochaeta, and its closest relatives were Spirochaeta isovalerica MA-2(T) (95.6% sequence identity) and Spirochaeta litoralis R1(T) (89.4%). 24860115 13 57 theme strain 1509:1514 arg1 MO-SPC1 1516:1522 strain MO-SPC1 1509:1522 strain MO-SPC1(T) 1509:1525 16S rRNA gene sequence-based phylogenetic analysis showed that strain MO-SPC1(T) was affiliated with the genus Spirochaeta, and its closest relatives were Spirochaeta isovalerica MA-2(T) (95.6% sequence identity) and Spirochaeta litoralis R1(T) (89.4%). 24860115 14 58 theme psychrophila 1906:1917 arg1 sp 1919:1920 the name Spirochaeta psychrophila sp 1885:1920 the name Spirochaeta psychrophila sp 1885:1920 Based on its phenotypic characteristics and phylogenetic traits, strain MO-SPC1(T) is placed in a separate taxon at the level of a novel species within the genus Spirochaeta, for which the name Spirochaeta psychrophila sp. 24860115 17 59 theme nature 2211:2216 arg1 report 2087:2092 the first report 2077:2092 the first report of an isolate of the phylum Spirochaetes from a deep-sea sedimentary environment, and of an obligately psychrophilic nature 2077:2216 To our knowledge, this is the first report of an isolate of the phylum Spirochaetes from a deep-sea sedimentary environment, and of an obligately psychrophilic nature. 24860115 17 59 theme nature 2211:2216 arg1 this 2069:2072 this 2069:2072 this 2069:2072 To our knowledge, this is the first report of an isolate of the phylum Spirochaetes from a deep-sea sedimentary environment, and of an obligately psychrophilic nature. 24860115 9 60 theme fatty 1065:1069 arg1 C 1101:1101 C(14 : 0) 1101:1109 C(14 : 0) 1101:1109 The major cellular fatty acids (>5% of the total) were C(14 : 0), C(16 : 0), iso-C(13 : 0), iso-C(14 : 0), iso-C(15 : 0), anteiso-C(13 : 0) and anteiso-C(15 : 0). 24860115 9 60 theme fatty 1065:1069 arg1 acids 1071:1075 The major cellular fatty acids 1046:1075 The major cellular fatty acids (>5% of the total) 1046:1094 The major cellular fatty acids (>5% of the total) were C(14 : 0), C(16 : 0), iso-C(13 : 0), iso-C(14 : 0), iso-C(15 : 0), anteiso-C(13 : 0) and anteiso-C(15 : 0). 24860115 14 61 theme name 1889:1892 arg1 sp 1919:1920 the name Spirochaeta psychrophila sp 1885:1920 the name Spirochaeta psychrophila sp 1885:1920 Based on its phenotypic characteristics and phylogenetic traits, strain MO-SPC1(T) is placed in a separate taxon at the level of a novel species within the genus Spirochaeta, for which the name Spirochaeta psychrophila sp. 24860115 13 62 theme phylogenetic 1475:1486 arg1 analysis 1488:1495 16S rRNA gene sequence-based phylogenetic analysis 1446:1495 16S rRNA gene sequence-based phylogenetic analysis 1446:1495 16S rRNA gene sequence-based phylogenetic analysis showed that strain MO-SPC1(T) was affiliated with the genus Spirochaeta, and its closest relatives were Spirochaeta isovalerica MA-2(T) (95.6% sequence identity) and Spirochaeta litoralis R1(T) (89.4%). 24860115 16 63 theme  = JCM 2018:2023 arg1 T 2046:2046 T 2046:2046 T 2046:2046 The type strain is MO-SPC1(T) ( = JCM 17280(T) = DSM 23951(T)). 24860115 16 63 theme  = JCM 2018:2023 arg1 23951 2040:2044  = JCM 17280(T) = DSM 23951 2018:2044  = JCM 17280(T) = DSM 23951(T) 2018:2047 The type strain is MO-SPC1(T) ( = JCM 17280(T) = DSM 23951(T)). 24860115 11 64 theme Isoprenoid 1360:1369 arg1 quinones 1371:1378 Isoprenoid quinones 1360:1378 Isoprenoid quinones 1360:1378 Isoprenoid quinones were not found. 24860115 14 65 theme separate 1798:1805 arg1 taxon 1807:1811 a separate taxon 1796:1811 a separate taxon 1796:1811 Based on its phenotypic characteristics and phylogenetic traits, strain MO-SPC1(T) is placed in a separate taxon at the level of a novel species within the genus Spirochaeta, for which the name Spirochaeta psychrophila sp. 24860115 2 66 theme continuous-flow 284:298 arg1 bioreactor 300:309 a continuous-flow bioreactor 282:309 a continuous-flow bioreactor 282:309 An obligately anaerobic, psychrophilic spirochaete, strain MO-SPC1(T), was isolated from a methanogenic microbial community grown in a continuous-flow bioreactor. 24860115 13 67 theme sequence 1640:1647 arg1 identity 1649:1656 95.6% sequence identity 1634:1656 95.6% sequence identity 1634:1656 16S rRNA gene sequence-based phylogenetic analysis showed that strain MO-SPC1(T) was affiliated with the genus Spirochaeta, and its closest relatives were Spirochaeta isovalerica MA-2(T) (95.6% sequence identity) and Spirochaeta litoralis R1(T) (89.4%). 24860115 13 67 theme sequence 1640:1647 arg1 MA-2 1625:1628 Spirochaeta isovalerica MA-2 1601:1628 Spirochaeta isovalerica MA-2(T) (95.6% sequence identity) 1601:1657 16S rRNA gene sequence-based phylogenetic analysis showed that strain MO-SPC1(T) was affiliated with the genus Spirochaeta, and its closest relatives were Spirochaeta isovalerica MA-2(T) (95.6% sequence identity) and Spirochaeta litoralis R1(T) (89.4%). 24860115 10 68 theme Spirochaeta 1347:1357 arg1 species 1326:1332 a species 1324:1332 a species of the genus Spirochaeta 1324:1357 To the best of our knowledge, this is the first report of the fatty acids iso-C(13 : 0) and anteiso-C(13 : 0) from a species of the genus Spirochaeta. 24860115 7 69 theme carbon 888:893 arg1 dioxide 895:901 carbon dioxide 888:901 carbon dioxide 888:901 The major end products of glucose fermentation were acetate, ethanol, hydrogen and carbon dioxide. 24860115 2 70 theme methanogenic 240:251 arg1 community 263:271 a methanogenic microbial community 238:271 a methanogenic microbial community grown in a continuous-flow bioreactor 238:309 An obligately anaerobic, psychrophilic spirochaete, strain MO-SPC1(T), was isolated from a methanogenic microbial community grown in a continuous-flow bioreactor. 24860115 16 71 theme type 1991:1994 arg1 strain 1996:2001 The type strain 1987:2001 The type strain 1987:2001 The type strain is MO-SPC1(T) ( = JCM 17280(T) = DSM 23951(T)). 24860115 16 71 theme type 1991:1994 arg1 MO-SPC1 2006:2012 MO-SPC1 2006:2012 MO-SPC1(T) ( = JCM 17280(T) = DSM 23951(T)) 2006:2048 The type strain is MO-SPC1(T) ( = JCM 17280(T) = DSM 23951(T)). 24860115 13 72 theme rRNA 1450:1453 arg1 analysis 1488:1495 16S rRNA gene sequence-based phylogenetic analysis 1446:1495 16S rRNA gene sequence-based phylogenetic analysis 1446:1495 16S rRNA gene sequence-based phylogenetic analysis showed that strain MO-SPC1(T) was affiliated with the genus Spirochaeta, and its closest relatives were Spirochaeta isovalerica MA-2(T) (95.6% sequence identity) and Spirochaeta litoralis R1(T) (89.4%). 24860115 1 73 theme Spirochaeta 136:146 arg1 description 111:121 emended description 103:121 emended description of the genus Spirochaeta 103:146 nov., a psychrophilic spirochaete isolated from subseafloor sediment, and emended description of the genus Spirochaeta. 24860115 1 73 theme Spirochaeta 136:146 arg1 spirochaete 51:61 a psychrophilic spirochaete 35:61 a psychrophilic spirochaete isolated from subseafloor sediment 35:96 nov., a psychrophilic spirochaete isolated from subseafloor sediment, and emended description of the genus Spirochaeta. 24860115 1 73 theme Spirochaeta 136:146 arg1 nov. 29:32 nov. 29:32 nov. 29:32 nov., a psychrophilic spirochaete isolated from subseafloor sediment, and emended description of the genus Spirochaeta. 24860115 2 74 attach isolated 224:231 arg2 MO-SPC1 208:214 strain MO-SPC1 201:214 strain MO-SPC1(T) 201:217 An obligately anaerobic, psychrophilic spirochaete, strain MO-SPC1(T), was isolated from a methanogenic microbial community grown in a continuous-flow bioreactor. 24860115 2 74 attach isolated 224:231 arg2 spirochaete 188:198 An obligately anaerobic, psychrophilic spirochaete 149:198 spirochaete 188:198 An obligately anaerobic, psychrophilic spirochaete, strain MO-SPC1(T), was isolated from a methanogenic microbial community grown in a continuous-flow bioreactor. 24860115 2 74 attach isolated 224:231 arg1 community 263:271 a methanogenic microbial community 238:271 a methanogenic microbial community grown in a continuous-flow bioreactor 238:309 An obligately anaerobic, psychrophilic spirochaete, strain MO-SPC1(T), was isolated from a methanogenic microbial community grown in a continuous-flow bioreactor. 24860115 5 75 dep pH 657:658 arg1 optimally 644:652 optimally 644:652 optimally 644:652 Strain MO-SPC1(T) grew at 0-18 °C (optimally at 15 °C), at pH 6.0-7.5 (optimally at pH 6.8-7.0) and in 20-70 g NaCl l(-1) (optimally at 30-40 NaCl l(-1)). 24860115 5 76 theme NaCl 684:687 arg1 l 720:720 optimally at 30-40 NaCl l(-1) 696:724 optimally at 30-40 NaCl l(-1) 696:724 Strain MO-SPC1(T) grew at 0-18 °C (optimally at 15 °C), at pH 6.0-7.5 (optimally at pH 6.8-7.0) and in 20-70 g NaCl l(-1) (optimally at 30-40 NaCl l(-1)). 24860115 5 76 theme NaCl 684:687 arg1 -1 691:692 -1 691:692 -1 691:692 Strain MO-SPC1(T) grew at 0-18 °C (optimally at 15 °C), at pH 6.0-7.5 (optimally at pH 6.8-7.0) and in 20-70 g NaCl l(-1) (optimally at 30-40 NaCl l(-1)). 24860115 5 76 theme NaCl 684:687 arg1 l 689:689 20-70 g NaCl l 676:689 20-70 g NaCl l(-1) (optimally at 30-40 NaCl l(-1)) 676:725 Strain MO-SPC1(T) grew at 0-18 °C (optimally at 15 °C), at pH 6.0-7.5 (optimally at pH 6.8-7.0) and in 20-70 g NaCl l(-1) (optimally at 30-40 NaCl l(-1)). 24860115 13 77 theme isovalerica 1613:1623 arg1 T 1630:1630 T 1630:1630 T 1630:1630 16S rRNA gene sequence-based phylogenetic analysis showed that strain MO-SPC1(T) was affiliated with the genus Spirochaeta, and its closest relatives were Spirochaeta isovalerica MA-2(T) (95.6% sequence identity) and Spirochaeta litoralis R1(T) (89.4%). 24860115 13 77 theme isovalerica 1613:1623 arg1 MA-2 1625:1628 Spirochaeta isovalerica MA-2 1601:1628 Spirochaeta isovalerica MA-2(T) (95.6% sequence identity) 1601:1657 16S rRNA gene sequence-based phylogenetic analysis showed that strain MO-SPC1(T) was affiliated with the genus Spirochaeta, and its closest relatives were Spirochaeta isovalerica MA-2(T) (95.6% sequence identity) and Spirochaeta litoralis R1(T) (89.4%). 24860115 13 77 theme isovalerica 1613:1623 arg1 identity 1649:1656 95.6% sequence identity 1634:1656 95.6% sequence identity 1634:1656 16S rRNA gene sequence-based phylogenetic analysis showed that strain MO-SPC1(T) was affiliated with the genus Spirochaeta, and its closest relatives were Spirochaeta isovalerica MA-2(T) (95.6% sequence identity) and Spirochaeta litoralis R1(T) (89.4%). 24860115 8 78 theme abundant 908:915 arg1 lipids 923:928 The abundant polar lipids 904:928 The abundant polar lipids of strain MO-SPC1(T) 904:949 The abundant polar lipids of strain MO-SPC1(T) were diphosphatidylglycerol, phosphatidylglycerol, unknown phospholipids and an unknown lipid. 24860115 8 78 theme abundant 908:915 arg1 diphosphatidylglycerol 956:977 diphosphatidylglycerol 956:977 diphosphatidylglycerol 956:977 The abundant polar lipids of strain MO-SPC1(T) were diphosphatidylglycerol, phosphatidylglycerol, unknown phospholipids and an unknown lipid. 24860115 7 79 theme fermentation 839:850 arg1 acetate 857:863 acetate 857:863 acetate 857:863 The major end products of glucose fermentation were acetate, ethanol, hydrogen and carbon dioxide. 24860115 7 79 theme fermentation 839:850 arg1 products 819:826 The major end products 805:826 The major end products of glucose fermentation 805:850 The major end products of glucose fermentation were acetate, ethanol, hydrogen and carbon dioxide. 24860115 3 80 theme subseafloor 357:367 arg1 sediments 369:377 subseafloor sediments 357:377 subseafloor sediments off the Shimokita Peninsula of Japan in the north-western Pacific Ocean 357:449 Originally, this community was obtained from subseafloor sediments off the Shimokita Peninsula of Japan in the north-western Pacific Ocean. 24860115 14 81 theme strain 1765:1770 arg1 T 1780:1780 T 1780:1780 T 1780:1780 Based on its phenotypic characteristics and phylogenetic traits, strain MO-SPC1(T) is placed in a separate taxon at the level of a novel species within the genus Spirochaeta, for which the name Spirochaeta psychrophila sp. 24860115 14 81 theme strain 1765:1770 arg1 MO-SPC1 1772:1778 strain MO-SPC1 1765:1778 strain MO-SPC1(T) 1765:1781 Based on its phenotypic characteristics and phylogenetic traits, strain MO-SPC1(T) is placed in a separate taxon at the level of a novel species within the genus Spirochaeta, for which the name Spirochaeta psychrophila sp. 24860115 15 82 theme psychrophilic 1961:1973 arg1 physiology 1975:1984 its true psychrophilic physiology 1952:1984 its true psychrophilic physiology 1952:1984 nov. is proposed, reflecting its true psychrophilic physiology. 24860115 17 83 theme psychrophilic 2197:2209 arg1 nature 2211:2216 an obligately psychrophilic nature 2183:2216 an obligately psychrophilic nature 2183:2216 To our knowledge, this is the first report of an isolate of the phylum Spirochaetes from a deep-sea sedimentary environment, and of an obligately psychrophilic nature. 24860115 0 84 theme psychrophila 12:23 arg1 sp 25:26 Spirochaeta psychrophila sp 0:26 Spirochaeta psychrophila sp. 0:27 Spirochaeta psychrophila sp. 24860115 13 85 theme closest 1578:1584 arg1 relatives 1586:1594 its closest relatives 1574:1594 its closest relatives 1574:1594 16S rRNA gene sequence-based phylogenetic analysis showed that strain MO-SPC1(T) was affiliated with the genus Spirochaeta, and its closest relatives were Spirochaeta isovalerica MA-2(T) (95.6% sequence identity) and Spirochaeta litoralis R1(T) (89.4%). 24860115 8 86 theme strain 933:938 arg1 T 948:948 T 948:948 T 948:948 The abundant polar lipids of strain MO-SPC1(T) were diphosphatidylglycerol, phosphatidylglycerol, unknown phospholipids and an unknown lipid. 24860115 8 86 theme strain 933:938 arg1 MO-SPC1 940:946 strain MO-SPC1 933:946 strain MO-SPC1(T) 933:949 The abundant polar lipids of strain MO-SPC1(T) were diphosphatidylglycerol, phosphatidylglycerol, unknown phospholipids and an unknown lipid. 24860115 5 87 theme Strain 573:578 arg1 MO-SPC1 580:586 Strain MO-SPC1 573:586 Strain MO-SPC1(T) 573:589 Strain MO-SPC1(T) grew at 0-18 °C (optimally at 15 °C), at pH 6.0-7.5 (optimally at pH 6.8-7.0) and in 20-70 g NaCl l(-1) (optimally at 30-40 NaCl l(-1)). 24860115 5 87 theme Strain 573:578 arg1 T 588:588 T 588:588 T 588:588 Strain MO-SPC1(T) grew at 0-18 °C (optimally at 15 °C), at pH 6.0-7.5 (optimally at pH 6.8-7.0) and in 20-70 g NaCl l(-1) (optimally at 30-40 NaCl l(-1)). 24860115 3 88 theme Shimokita 387:395 arg1 Peninsula 397:405 the Shimokita Peninsula 383:405 the Shimokita Peninsula of Japan in the north-western Pacific Ocean 383:449 Originally, this community was obtained from subseafloor sediments off the Shimokita Peninsula of Japan in the north-western Pacific Ocean. 24860115 3 89 theme north-western 423:435 arg1 Ocean 445:449 the north-western Pacific Ocean 419:449 the north-western Pacific Ocean 419:449 Originally, this community was obtained from subseafloor sediments off the Shimokita Peninsula of Japan in the north-western Pacific Ocean. 24860115 17 90 theme phylum 2115:2120 arg1 Spirochaetes 2122:2133 the phylum Spirochaetes 2111:2133 the phylum Spirochaetes from a deep-sea sedimentary environment 2111:2173 To our knowledge, this is the first report of an isolate of the phylum Spirochaetes from a deep-sea sedimentary environment, and of an obligately psychrophilic nature. 24860115 4 91 theme µm 569:570 arg1 wavelength 533:542 a wavelength 531:542 a wavelength of approximately 0.5-0.6 µm 531:570 The cells were motile, Gram-stain-negative, helical, 0.25-0.55×3.6-15 µm, with a wavelength of approximately 0.5-0.6 µm. 24860115 14 92 theme phenotypic 1713:1722 arg1 characteristics 1724:1738 its phenotypic characteristics 1709:1738 its phenotypic characteristics 1709:1738 Based on its phenotypic characteristics and phylogenetic traits, strain MO-SPC1(T) is placed in a separate taxon at the level of a novel species within the genus Spirochaeta, for which the name Spirochaeta psychrophila sp. 24860115 4 93 dep motile 467:472 arg1 Gram-stain-negative 475:493 Gram-stain-negative 475:493 Gram-stain-negative 475:493 The cells were motile, Gram-stain-negative, helical, 0.25-0.55×3.6-15 µm, with a wavelength of approximately 0.5-0.6 µm. 24860115 4 93 dep motile 467:472 arg1 helical 496:502 helical 496:502 helical 496:502 The cells were motile, Gram-stain-negative, helical, 0.25-0.55×3.6-15 µm, with a wavelength of approximately 0.5-0.6 µm. 24860115 12 94 theme DNA 1427:1429 arg1 % 1443:1443 39.8 mol% 1435:1443 39.8 mol% 1435:1443 The G+C content of the genomic DNA was 39.8 mol%. 24860115 12 94 theme DNA 1427:1429 arg1 content 1404:1410 The G+C content 1396:1410 The G+C content of the genomic DNA 1396:1429 The G+C content of the genomic DNA was 39.8 mol%. 24860115 10 95 theme fatty 1271:1275 arg1 acids 1277:1281 the fatty acids iso-C(13 : 0) and anteiso-C(13 : 0) 1267:1317 the fatty acids iso-C(13 : 0) and anteiso-C(13 : 0) 1267:1317 To the best of our knowledge, this is the first report of the fatty acids iso-C(13 : 0) and anteiso-C(13 : 0) from a species of the genus Spirochaeta. 24860115 10 95 theme fatty 1271:1275 arg1 iso-C 1283:1287 iso-C 1283:1287 iso-C 1283:1287 To the best of our knowledge, this is the first report of the fatty acids iso-C(13 : 0) and anteiso-C(13 : 0) from a species of the genus Spirochaeta. 24860115 10 95 theme fatty 1271:1275 arg1 anteiso-C 1301:1309 anteiso-C 1301:1309 anteiso-C 1301:1309 To the best of our knowledge, this is the first report of the fatty acids iso-C(13 : 0) and anteiso-C(13 : 0) from a species of the genus Spirochaeta. 24860115 17 96 theme deep-sea 2142:2149 arg1 environment 2163:2173 a deep-sea sedimentary environment 2140:2173 a deep-sea sedimentary environment 2140:2173 To our knowledge, this is the first report of an isolate of the phylum Spirochaetes from a deep-sea sedimentary environment, and of an obligately psychrophilic nature. 24860115 13 97 theme genus 1551:1555 arg1 Spirochaeta 1557:1567 the genus Spirochaeta 1547:1567 the genus Spirochaeta 1547:1567 16S rRNA gene sequence-based phylogenetic analysis showed that strain MO-SPC1(T) was affiliated with the genus Spirochaeta, and its closest relatives were Spirochaeta isovalerica MA-2(T) (95.6% sequence identity) and Spirochaeta litoralis R1(T) (89.4%). 24860115 13 98 theme % 1638:1638 arg1 identity 1649:1656 95.6% sequence identity 1634:1656 95.6% sequence identity 1634:1656 16S rRNA gene sequence-based phylogenetic analysis showed that strain MO-SPC1(T) was affiliated with the genus Spirochaeta, and its closest relatives were Spirochaeta isovalerica MA-2(T) (95.6% sequence identity) and Spirochaeta litoralis R1(T) (89.4%). 24860115 13 98 theme % 1638:1638 arg1 MA-2 1625:1628 Spirochaeta isovalerica MA-2 1601:1628 Spirochaeta isovalerica MA-2(T) (95.6% sequence identity) 1601:1657 16S rRNA gene sequence-based phylogenetic analysis showed that strain MO-SPC1(T) was affiliated with the genus Spirochaeta, and its closest relatives were Spirochaeta isovalerica MA-2(T) (95.6% sequence identity) and Spirochaeta litoralis R1(T) (89.4%). 24860115 2 99 theme strain 201:206 arg1 T 216:216 T 216:216 T 216:216 An obligately anaerobic, psychrophilic spirochaete, strain MO-SPC1(T), was isolated from a methanogenic microbial community grown in a continuous-flow bioreactor. 24860115 2 99 theme strain 201:206 arg1 spirochaete 188:198 An obligately anaerobic, psychrophilic spirochaete 149:198 spirochaete 188:198 An obligately anaerobic, psychrophilic spirochaete, strain MO-SPC1(T), was isolated from a methanogenic microbial community grown in a continuous-flow bioreactor. 24860115 2 99 theme strain 201:206 arg1 MO-SPC1 208:214 strain MO-SPC1 201:214 strain MO-SPC1(T) 201:217 An obligately anaerobic, psychrophilic spirochaete, strain MO-SPC1(T), was isolated from a methanogenic microbial community grown in a continuous-flow bioreactor. 24860115 14 100 theme genus 1856:1860 arg1 Spirochaeta 1862:1872 the genus Spirochaeta 1852:1872 the genus Spirochaeta 1852:1872 Based on its phenotypic characteristics and phylogenetic traits, strain MO-SPC1(T) is placed in a separate taxon at the level of a novel species within the genus Spirochaeta, for which the name Spirochaeta psychrophila sp. 24860115 8 101 theme unknown 1002:1008 arg1 phospholipids 1010:1022 unknown phospholipids 1002:1022 unknown phospholipids 1002:1022 The abundant polar lipids of strain MO-SPC1(T) were diphosphatidylglycerol, phosphatidylglycerol, unknown phospholipids and an unknown lipid. 24860115 17 102 from environment 2163:2173 arg1 isolate 2100:2106 an isolate 2097:2106 an isolate of the phylum Spirochaetes from a deep-sea sedimentary environment 2097:2173 To our knowledge, this is the first report of an isolate of the phylum Spirochaetes from a deep-sea sedimentary environment, and of an obligately psychrophilic nature. 24860115 17 102 from environment 2163:2173 arg1 Spirochaetes 2122:2133 the phylum Spirochaetes 2111:2133 the phylum Spirochaetes from a deep-sea sedimentary environment 2111:2173 To our knowledge, this is the first report of an isolate of the phylum Spirochaetes from a deep-sea sedimentary environment, and of an obligately psychrophilic nature. 24860115 17 103 theme isolate 2100:2106 arg1 report 2087:2092 the first report 2077:2092 the first report of an isolate of the phylum Spirochaetes from a deep-sea sedimentary environment, and of an obligately psychrophilic nature 2077:2216 To our knowledge, this is the first report of an isolate of the phylum Spirochaetes from a deep-sea sedimentary environment, and of an obligately psychrophilic nature. 24860115 17 103 theme isolate 2100:2106 arg1 this 2069:2072 this 2069:2072 this 2069:2072 To our knowledge, this is the first report of an isolate of the phylum Spirochaetes from a deep-sea sedimentary environment, and of an obligately psychrophilic nature. 24860115 16 104 dep MO-SPC1 2006:2012 arg1 T 2046:2046 T 2046:2046 T 2046:2046 The type strain is MO-SPC1(T) ( = JCM 17280(T) = DSM 23951(T)). 24860115 16 104 dep MO-SPC1 2006:2012 arg1 23951 2040:2044  = JCM 17280(T) = DSM 23951 2018:2044  = JCM 17280(T) = DSM 23951(T) 2018:2047 The type strain is MO-SPC1(T) ( = JCM 17280(T) = DSM 23951(T)). 26407813 4 0 theme Gallionella-like 766:781 arg1 oxides 758:763 biogenic iron oxides 744:763 biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM) 744:912 We (i) identified and quantified FeOB in water and sediment at the outflow, terraces, and creek, (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM), and (iii) examined the metal distribution in sediments. 26407813 4 0 theme Gallionella-like 766:781 arg1 stalks 791:796 Gallionella-like twisted stalks 766:796 Gallionella-like twisted stalks 766:796 We (i) identified and quantified FeOB in water and sediment at the outflow, terraces, and creek, (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM), and (iii) examined the metal distribution in sediments. 26407813 2 1 theme microoxic 331:339 arg1 groundwater 341:351 microoxic groundwater 331:351 microoxic groundwater with ~5 mm Fe(II) 331:369 The transition from microoxic groundwater with ~5 mm Fe(II) to oxic surface water may provide a suitable habitat for microaerobic iron-oxidizing bacteria (FeOB). 26407813 1 2 theme creek 243:247 arg1 bank 249:252 a creek bank 241:252 a creek bank in a former uranium-mining area near Ronneburg, Germany 241:308 Heavy metal-contaminated, pH 6 mine water discharge created new streams and iron-rich terraces at a creek bank in a former uranium-mining area near Ronneburg, Germany. 26407813 9 3 theme stalk 1464:1468 arg1 formers 1470:1476 known stalk formers 1458:1476 known stalk formers such as Gallionella ferruginea and Gallionellaceae strain R-1 1458:1538 Classical 16S rRNA gene cloning showed that 96% of the Gallionella-related sequences had ≥ 97% identity to the putatively metal-tolerant 'Gallionella capsiferriformans ES-2', in addition to known stalk formers such as Gallionella ferruginea and Gallionellaceae strain R-1. 26407813 9 3 theme stalk 1464:1468 arg1 Gallionellaceae 1513:1527 Gallionellaceae 1513:1527 Gallionellaceae 1513:1527 Classical 16S rRNA gene cloning showed that 96% of the Gallionella-related sequences had ≥ 97% identity to the putatively metal-tolerant 'Gallionella capsiferriformans ES-2', in addition to known stalk formers such as Gallionella ferruginea and Gallionellaceae strain R-1. 26407813 9 3 theme stalk 1464:1468 arg1 ferruginea 1498:1507 ferruginea 1498:1507 ferruginea 1498:1507 Classical 16S rRNA gene cloning showed that 96% of the Gallionella-related sequences had ≥ 97% identity to the putatively metal-tolerant 'Gallionella capsiferriformans ES-2', in addition to known stalk formers such as Gallionella ferruginea and Gallionellaceae strain R-1. 26407813 0 4 with association 61:71 arg1 stalks 95:100 Gallionella-like stalks 78:100 Gallionella-like stalks in metal-rich pH 6 mine water discharge 78:140 Dominance of 'Gallionella capsiferriformans' and heavy metal association with Gallionella-like stalks in metal-rich pH 6 mine water discharge. 26407813 11 5 theme metals 1837:1842 arg1 association 1816:1826 the association 1812:1826 the association of heavy metals with biogenic iron oxides and the potential for metal retention by these stalks 1812:1922 SEM and scanning TEM-energy-dispersive X-ray spectroscopy revealed that stalk material contained Cu and Sn, demonstrating the association of heavy metals with biogenic iron oxides and the potential for metal retention by these stalks. 26407813 5 6 theme 6-month 1062:1068 arg1 period 1076:1081 a 6-month study period 1060:1081 a 6-month study period 1060:1081 Using quantitative PCR, a very high abundance of FeOB was demonstrated at all sites over a 6-month study period. 26407813 4 7 theme biogenic 744:751 arg1 oxides 758:763 biogenic iron oxides 744:763 biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM) 744:912 We (i) identified and quantified FeOB in water and sediment at the outflow, terraces, and creek, (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM), and (iii) examined the metal distribution in sediments. 26407813 4 7 theme biogenic 744:751 arg1 stalks 791:796 Gallionella-like twisted stalks 766:796 Gallionella-like twisted stalks 766:796 We (i) identified and quantified FeOB in water and sediment at the outflow, terraces, and creek, (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM), and (iii) examined the metal distribution in sediments. 26407813 12 8 theme sediments 1950:1958 arg1 extraction 1936:1945 Sequential extraction 1925:1945 Sequential extraction of sediments 1925:1958 Sequential extraction of sediments suggested that Cu (52-61% of total sediment Cu) and other heavy metals were primarily bound to the iron oxide fractions. 26407813 7 9 with communities 1123:1133 arg1 contribution 1187:1198 a minor contribution 1179:1198 a minor contribution of other FeOB such as Sideroxydans spp 1179:1237 clearly dominated the communities, accounting for up to 88% of Bacteria, with a minor contribution of other FeOB such as Sideroxydans spp. 26407813 10 10 theme glass 1561:1565 arg1 slides 1567:1572 glass slides 1561:1572 glass slides incubated in water and sediment 1561:1604 Twisted stalks from glass slides incubated in water and sediment were composed of the Fe(III) oxyhydroxide ferrihydrite, as well as polysaccharides. 26407813 13 11 theme G. 2119:2120 arg1 capsiferriformans 2122:2138 G. capsiferriformans 2119:2138 'G. capsiferriformans' 2118:2139 These results show the importance of 'G. capsiferriformans' and biogenic iron oxides in slightly acidic but highly metal-contaminated freshwater environments. 26407813 4 12 theme oxides 758:763 arg1 terraces 691:698 terraces 691:698 terraces 691:698 We (i) identified and quantified FeOB in water and sediment at the outflow, terraces, and creek, (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM), and (iii) examined the metal distribution in sediments. 26407813 4 12 theme oxides 758:763 arg1 creek 705:709 creek 705:709 creek 705:709 We (i) identified and quantified FeOB in water and sediment at the outflow, terraces, and creek, (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM), and (iii) examined the metal distribution in sediments. 26407813 4 12 theme oxides 758:763 arg1 FeOB 648:651 quantified FeOB 637:651 quantified FeOB in water and sediment at the outflow 637:688 We (i) identified and quantified FeOB in water and sediment at the outflow, terraces, and creek, (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM), and (iii) examined the metal distribution in sediments. 26407813 4 12 theme oxides 758:763 arg1 composition 729:739 the composition 725:739 (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM) 712:912 We (i) identified and quantified FeOB in water and sediment at the outflow, terraces, and creek, (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM), and (iii) examined the metal distribution in sediments. 26407813 1 13 theme water 179:183 arg1 metal-contaminated 149:166 metal-contaminated 149:166 metal-contaminated 149:166 Heavy metal-contaminated, pH 6 mine water discharge created new streams and iron-rich terraces at a creek bank in a former uranium-mining area near Ronneburg, Germany. 26407813 1 13 theme water 179:183 arg1 discharge 185:193 pH 6 mine water discharge 169:193 pH 6 mine water discharge 169:193 Heavy metal-contaminated, pH 6 mine water discharge created new streams and iron-rich terraces at a creek bank in a former uranium-mining area near Ronneburg, Germany. 26407813 4 14 theme electron 830:837 arg1 SEM 851:853 SEM 851:853 SEM 851:853 We (i) identified and quantified FeOB in water and sediment at the outflow, terraces, and creek, (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM), and (iii) examined the metal distribution in sediments. 26407813 4 14 theme electron 830:837 arg1 microscopy 839:848 scanning and transmission electron microscopy 804:848 microscopy 839:848 We (i) identified and quantified FeOB in water and sediment at the outflow, terraces, and creek, (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM), and (iii) examined the metal distribution in sediments. 26407813 3 15 theme potential 508:516 arg1 contribution 518:529 the potential contribution 504:529 the potential contribution of these FeOB to iron oxidation and metal retention in this high-metal environment 504:612 In this study, we investigated the potential contribution of these FeOB to iron oxidation and metal retention in this high-metal environment. 26407813 9 16 theme gene 1287:1290 arg1 cloning 1292:1298 Classical 16S rRNA gene cloning 1268:1298 Classical 16S rRNA gene cloning 1268:1298 Classical 16S rRNA gene cloning showed that 96% of the Gallionella-related sequences had ≥ 97% identity to the putatively metal-tolerant 'Gallionella capsiferriformans ES-2', in addition to known stalk formers such as Gallionella ferruginea and Gallionellaceae strain R-1. 26407813 11 17 contain contained 1777:1785 arg1 material 1768:1775 stalk material 1762:1775 stalk material 1762:1775 SEM and scanning TEM-energy-dispersive X-ray spectroscopy revealed that stalk material contained Cu and Sn, demonstrating the association of heavy metals with biogenic iron oxides and the potential for metal retention by these stalks. 26407813 11 17 contain contained 1777:1785 arg2 Sn 1794:1795 Sn 1794:1795 Sn 1794:1795 SEM and scanning TEM-energy-dispersive X-ray spectroscopy revealed that stalk material contained Cu and Sn, demonstrating the association of heavy metals with biogenic iron oxides and the potential for metal retention by these stalks. 26407813 11 17 contain contained 1777:1785 arg2 Cu 1787:1788 Cu 1787:1788 Cu 1787:1788 SEM and scanning TEM-energy-dispersive X-ray spectroscopy revealed that stalk material contained Cu and Sn, demonstrating the association of heavy metals with biogenic iron oxides and the potential for metal retention by these stalks. 26407813 9 18 theme strain 1529:1534 arg1 R-1 1536:1538 strain R-1 1529:1538 strain R-1 1529:1538 Classical 16S rRNA gene cloning showed that 96% of the Gallionella-related sequences had ≥ 97% identity to the putatively metal-tolerant 'Gallionella capsiferriformans ES-2', in addition to known stalk formers such as Gallionella ferruginea and Gallionellaceae strain R-1. 26407813 7 19 theme FeOB 1209:1212 arg1 contribution 1187:1198 a minor contribution 1179:1198 a minor contribution of other FeOB such as Sideroxydans spp 1179:1237 clearly dominated the communities, accounting for up to 88% of Bacteria, with a minor contribution of other FeOB such as Sideroxydans spp. 26407813 11 20 theme scanning 1698:1705 arg1 spectroscopy 1735:1746 SEM and scanning TEM-energy-dispersive X-ray spectroscopy 1690:1746 spectroscopy 1735:1746 SEM and scanning TEM-energy-dispersive X-ray spectroscopy revealed that stalk material contained Cu and Sn, demonstrating the association of heavy metals with biogenic iron oxides and the potential for metal retention by these stalks. 26407813 4 21 dep SEM 851:853 arg1 TEM 856:858 TEM 856:858 TEM 856:858 We (i) identified and quantified FeOB in water and sediment at the outflow, terraces, and creek, (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM), and (iii) examined the metal distribution in sediments. 26407813 3 22 theme iron 548:551 arg1 oxidation 553:561 iron oxidation 548:561 iron oxidation 548:561 In this study, we investigated the potential contribution of these FeOB to iron oxidation and metal retention in this high-metal environment. 26407813 4 23 from composition 729:739 arg1 sediment 666:673 sediment 666:673 sediment 666:673 We (i) identified and quantified FeOB in water and sediment at the outflow, terraces, and creek, (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM), and (iii) examined the metal distribution in sediments. 26407813 4 23 from composition 729:739 arg1 outflow 682:688 the outflow 678:688 the outflow 678:688 We (i) identified and quantified FeOB in water and sediment at the outflow, terraces, and creek, (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM), and (iii) examined the metal distribution in sediments. 26407813 4 23 from composition 729:739 arg1 water 656:660 water 656:660 water 656:660 We (i) identified and quantified FeOB in water and sediment at the outflow, terraces, and creek, (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM), and (iii) examined the metal distribution in sediments. 26407813 3 24 theme FeOB 540:543 arg1 contribution 518:529 the potential contribution 504:529 the potential contribution of these FeOB to iron oxidation and metal retention in this high-metal environment 504:612 In this study, we investigated the potential contribution of these FeOB to iron oxidation and metal retention in this high-metal environment. 26407813 4 25 from distribution 944:955 arg1 sediments 960:968 sediments 960:968 sediments 960:968 We (i) identified and quantified FeOB in water and sediment at the outflow, terraces, and creek, (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM), and (iii) examined the metal distribution in sediments. 26407813 10 26 from slides 1567:1572 arg1 stalks 1549:1554 Twisted stalks 1541:1554 Twisted stalks from glass slides incubated in water and sediment 1541:1604 Twisted stalks from glass slides incubated in water and sediment were composed of the Fe(III) oxyhydroxide ferrihydrite, as well as polysaccharides. 26407813 11 27 theme metal 1892:1896 arg1 retention 1898:1906 metal retention 1892:1906 metal retention by these stalks 1892:1922 SEM and scanning TEM-energy-dispersive X-ray spectroscopy revealed that stalk material contained Cu and Sn, demonstrating the association of heavy metals with biogenic iron oxides and the potential for metal retention by these stalks. 26407813 10 28 theme oxyhydroxide 1635:1646 arg1 ferrihydrite 1648:1659 the Fe(III) oxyhydroxide ferrihydrite 1623:1659 the Fe(III) oxyhydroxide ferrihydrite 1623:1659 Twisted stalks from glass slides incubated in water and sediment were composed of the Fe(III) oxyhydroxide ferrihydrite, as well as polysaccharides. 26407813 7 29 theme minor 1181:1185 arg1 contribution 1187:1198 a minor contribution 1179:1198 a minor contribution of other FeOB such as Sideroxydans spp 1179:1237 clearly dominated the communities, accounting for up to 88% of Bacteria, with a minor contribution of other FeOB such as Sideroxydans spp. 26407813 0 30 from stalks 95:100 arg1 discharge 132:140 metal-rich pH 6 mine water discharge 105:140 metal-rich pH 6 mine water discharge 105:140 Dominance of 'Gallionella capsiferriformans' and heavy metal association with Gallionella-like stalks in metal-rich pH 6 mine water discharge. 26407813 0 31 theme metal 55:59 arg1 association 61:71 heavy metal association 49:71 heavy metal association with Gallionella-like stalks in metal-rich pH 6 mine water discharge 49:140 Dominance of 'Gallionella capsiferriformans' and heavy metal association with Gallionella-like stalks in metal-rich pH 6 mine water discharge. 26407813 9 32 theme Gallionella-related 1323:1341 arg1 sequences 1343:1351 the Gallionella-related sequences 1319:1351 the Gallionella-related sequences 1319:1351 Classical 16S rRNA gene cloning showed that 96% of the Gallionella-related sequences had ≥ 97% identity to the putatively metal-tolerant 'Gallionella capsiferriformans ES-2', in addition to known stalk formers such as Gallionella ferruginea and Gallionellaceae strain R-1. 26407813 4 33 with oxides 758:763 arg1 microscopy 896:905 confocal laser scanning microscopy 872:905 scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM) 804:912 We (i) identified and quantified FeOB in water and sediment at the outflow, terraces, and creek, (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM), and (iii) examined the metal distribution in sediments. 26407813 4 33 with oxides 758:763 arg1 SEM 851:853 SEM 851:853 SEM 851:853 We (i) identified and quantified FeOB in water and sediment at the outflow, terraces, and creek, (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM), and (iii) examined the metal distribution in sediments. 26407813 4 33 with oxides 758:763 arg1 microscopy 839:848 scanning and transmission electron microscopy 804:848 microscopy 839:848 We (i) identified and quantified FeOB in water and sediment at the outflow, terraces, and creek, (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM), and (iii) examined the metal distribution in sediments. 26407813 4 33 with oxides 758:763 arg1 CLSM 908:911 CLSM 908:911 CLSM 908:911 We (i) identified and quantified FeOB in water and sediment at the outflow, terraces, and creek, (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM), and (iii) examined the metal distribution in sediments. 26407813 4 34 theme confocal 872:879 arg1 microscopy 896:905 confocal laser scanning microscopy 872:905 scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM) 804:912 We (i) identified and quantified FeOB in water and sediment at the outflow, terraces, and creek, (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM), and (iii) examined the metal distribution in sediments. 26407813 4 34 theme confocal 872:879 arg1 CLSM 908:911 CLSM 908:911 CLSM 908:911 We (i) identified and quantified FeOB in water and sediment at the outflow, terraces, and creek, (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM), and (iii) examined the metal distribution in sediments. 26407813 4 35 theme quantified 637:646 arg1 FeOB 648:651 quantified FeOB 637:651 quantified FeOB in water and sediment at the outflow 637:688 We (i) identified and quantified FeOB in water and sediment at the outflow, terraces, and creek, (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM), and (iii) examined the metal distribution in sediments. 26407813 4 36 dep examined 925:932 arg1 iii 920:922 iii 920:922 iii 920:922 We (i) identified and quantified FeOB in water and sediment at the outflow, terraces, and creek, (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM), and (iii) examined the metal distribution in sediments. 26407813 4 37 from terraces 691:698 arg1 sediment 666:673 sediment 666:673 sediment 666:673 We (i) identified and quantified FeOB in water and sediment at the outflow, terraces, and creek, (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM), and (iii) examined the metal distribution in sediments. 26407813 4 37 from terraces 691:698 arg1 outflow 682:688 the outflow 678:688 the outflow 678:688 We (i) identified and quantified FeOB in water and sediment at the outflow, terraces, and creek, (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM), and (iii) examined the metal distribution in sediments. 26407813 4 37 from terraces 691:698 arg1 water 656:660 water 656:660 water 656:660 We (i) identified and quantified FeOB in water and sediment at the outflow, terraces, and creek, (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM), and (iii) examined the metal distribution in sediments. 26407813 9 38 theme 97 1359:1360 arg1 % 1361:1361 % 1361:1361 % 1361:1361 Classical 16S rRNA gene cloning showed that 96% of the Gallionella-related sequences had ≥ 97% identity to the putatively metal-tolerant 'Gallionella capsiferriformans ES-2', in addition to known stalk formers such as Gallionella ferruginea and Gallionellaceae strain R-1. 26407813 11 39 theme stalk 1762:1766 arg1 material 1768:1775 stalk material 1762:1775 stalk material 1762:1775 SEM and scanning TEM-energy-dispersive X-ray spectroscopy revealed that stalk material contained Cu and Sn, demonstrating the association of heavy metals with biogenic iron oxides and the potential for metal retention by these stalks. 26407813 11 40 theme TEM-energy-dispersive 1707:1727 arg1 spectroscopy 1735:1746 SEM and scanning TEM-energy-dispersive X-ray spectroscopy 1690:1746 spectroscopy 1735:1746 SEM and scanning TEM-energy-dispersive X-ray spectroscopy revealed that stalk material contained Cu and Sn, demonstrating the association of heavy metals with biogenic iron oxides and the potential for metal retention by these stalks. 26407813 0 41 theme metal-rich 105:114 arg1 discharge 132:140 metal-rich pH 6 mine water discharge 105:140 metal-rich pH 6 mine water discharge 105:140 Dominance of 'Gallionella capsiferriformans' and heavy metal association with Gallionella-like stalks in metal-rich pH 6 mine water discharge. 26407813 2 42 theme microaerobic 428:439 arg1 FeOB 466:469 FeOB 466:469 FeOB 466:469 The transition from microoxic groundwater with ~5 mm Fe(II) to oxic surface water may provide a suitable habitat for microaerobic iron-oxidizing bacteria (FeOB). 26407813 2 42 theme microaerobic 428:439 arg1 bacteria 456:463 microaerobic iron-oxidizing bacteria 428:463 microaerobic iron-oxidizing bacteria (FeOB) 428:470 The transition from microoxic groundwater with ~5 mm Fe(II) to oxic surface water may provide a suitable habitat for microaerobic iron-oxidizing bacteria (FeOB). 26407813 4 43 from outflow 682:688 arg1 water 656:660 water 656:660 water 656:660 We (i) identified and quantified FeOB in water and sediment at the outflow, terraces, and creek, (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM), and (iii) examined the metal distribution in sediments. 26407813 4 43 from outflow 682:688 arg1 terraces 691:698 terraces 691:698 terraces 691:698 We (i) identified and quantified FeOB in water and sediment at the outflow, terraces, and creek, (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM), and (iii) examined the metal distribution in sediments. 26407813 4 43 from outflow 682:688 arg1 sediment 666:673 sediment 666:673 sediment 666:673 We (i) identified and quantified FeOB in water and sediment at the outflow, terraces, and creek, (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM), and (iii) examined the metal distribution in sediments. 26407813 4 43 from outflow 682:688 arg1 composition 729:739 the composition 725:739 (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM) 712:912 We (i) identified and quantified FeOB in water and sediment at the outflow, terraces, and creek, (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM), and (iii) examined the metal distribution in sediments. 26407813 4 43 from outflow 682:688 arg1 creek 705:709 creek 705:709 creek 705:709 We (i) identified and quantified FeOB in water and sediment at the outflow, terraces, and creek, (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM), and (iii) examined the metal distribution in sediments. 26407813 4 43 from outflow 682:688 arg1 FeOB 648:651 quantified FeOB 637:651 quantified FeOB in water and sediment at the outflow 637:688 We (i) identified and quantified FeOB in water and sediment at the outflow, terraces, and creek, (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM), and (iii) examined the metal distribution in sediments. 26407813 12 44 dep Cu 1975:1976 arg1 % 1984:1984 52-61% 1979:1984 52-61% of total sediment Cu 1979:2005 Sequential extraction of sediments suggested that Cu (52-61% of total sediment Cu) and other heavy metals were primarily bound to the iron oxide fractions. 26407813 12 44 dep Cu 1975:1976 arg1 Cu 2004:2005 total sediment Cu 1989:2005 total sediment Cu 1989:2005 Sequential extraction of sediments suggested that Cu (52-61% of total sediment Cu) and other heavy metals were primarily bound to the iron oxide fractions. 26407813 12 45 theme iron 2059:2062 arg1 fractions 2070:2078 the iron oxide fractions 2055:2078 the iron oxide fractions 2055:2078 Sequential extraction of sediments suggested that Cu (52-61% of total sediment Cu) and other heavy metals were primarily bound to the iron oxide fractions. 26407813 9 46 dep formers 1470:1476 arg1 addition 1446:1453 addition 1446:1453 addition 1446:1453 Classical 16S rRNA gene cloning showed that 96% of the Gallionella-related sequences had ≥ 97% identity to the putatively metal-tolerant 'Gallionella capsiferriformans ES-2', in addition to known stalk formers such as Gallionella ferruginea and Gallionellaceae strain R-1. 26407813 13 47 theme metal-contaminated 2196:2213 arg1 environments 2226:2237 slightly acidic but highly metal-contaminated freshwater environments 2169:2237 slightly acidic but highly metal-contaminated freshwater environments 2169:2237 These results show the importance of 'G. capsiferriformans' and biogenic iron oxides in slightly acidic but highly metal-contaminated freshwater environments. 26407813 12 48 theme heavy 2018:2022 arg1 metals 2024:2029 other heavy metals 2012:2029 other heavy metals 2012:2029 Sequential extraction of sediments suggested that Cu (52-61% of total sediment Cu) and other heavy metals were primarily bound to the iron oxide fractions. 26407813 12 49 theme total 1989:1993 arg1 Cu 2004:2005 total sediment Cu 1989:2005 total sediment Cu 1989:2005 Sequential extraction of sediments suggested that Cu (52-61% of total sediment Cu) and other heavy metals were primarily bound to the iron oxide fractions. 26407813 2 50 theme surface 379:385 arg1 water 387:391 oxic surface water 374:391 oxic surface water 374:391 The transition from microoxic groundwater with ~5 mm Fe(II) to oxic surface water may provide a suitable habitat for microaerobic iron-oxidizing bacteria (FeOB). 26407813 1 51 theme uranium-mining 266:279 arg1 area 281:284 a former uranium-mining area 257:284 a former uranium-mining area near Ronneburg, Germany 257:308 Heavy metal-contaminated, pH 6 mine water discharge created new streams and iron-rich terraces at a creek bank in a former uranium-mining area near Ronneburg, Germany. 26407813 13 52 theme capsiferriformans 2122:2138 arg1 importance 2104:2113 the importance 2100:2113 the importance of 'G. capsiferriformans' and biogenic iron oxides in slightly acidic but highly metal-contaminated freshwater environments 2100:2237 These results show the importance of 'G. capsiferriformans' and biogenic iron oxides in slightly acidic but highly metal-contaminated freshwater environments. 26407813 9 53 theme metal-tolerant 1390:1403 arg1 ES-2 1436:1439 the putatively metal-tolerant 'Gallionella capsiferriformans ES-2' 1375:1440 the putatively metal-tolerant 'Gallionella capsiferriformans ES-2' 1375:1440 Classical 16S rRNA gene cloning showed that 96% of the Gallionella-related sequences had ≥ 97% identity to the putatively metal-tolerant 'Gallionella capsiferriformans ES-2', in addition to known stalk formers such as Gallionella ferruginea and Gallionellaceae strain R-1. 26407813 4 54 theme scanning 887:894 arg1 microscopy 896:905 confocal laser scanning microscopy 872:905 scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM) 804:912 We (i) identified and quantified FeOB in water and sediment at the outflow, terraces, and creek, (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM), and (iii) examined the metal distribution in sediments. 26407813 4 54 theme scanning 887:894 arg1 CLSM 908:911 CLSM 908:911 CLSM 908:911 We (i) identified and quantified FeOB in water and sediment at the outflow, terraces, and creek, (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM), and (iii) examined the metal distribution in sediments. 26407813 4 55 theme studied 717:723 arg1 composition 729:739 the composition 725:739 (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM) 712:912 We (i) identified and quantified FeOB in water and sediment at the outflow, terraces, and creek, (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM), and (iii) examined the metal distribution in sediments. 26407813 0 56 theme capsiferriformans 26:42 arg1 Dominance 0:8 Dominance 0:8 Dominance of 'Gallionella capsiferriformans' 0:43 Dominance of 'Gallionella capsiferriformans' and heavy metal association with Gallionella-like stalks in metal-rich pH 6 mine water discharge. 26407813 0 56 theme capsiferriformans 26:42 arg1 association 61:71 heavy metal association 49:71 heavy metal association with Gallionella-like stalks in metal-rich pH 6 mine water discharge 49:140 Dominance of 'Gallionella capsiferriformans' and heavy metal association with Gallionella-like stalks in metal-rich pH 6 mine water discharge. 26407813 5 57 theme high 1002:1005 arg1 abundance 1007:1015 a very high abundance 995:1015 a very high abundance of FeOB 995:1023 Using quantitative PCR, a very high abundance of FeOB was demonstrated at all sites over a 6-month study period. 26407813 9 58 dep ferruginea 1498:1507 arg1 R-1 1536:1538 strain R-1 1529:1538 strain R-1 1529:1538 Classical 16S rRNA gene cloning showed that 96% of the Gallionella-related sequences had ≥ 97% identity to the putatively metal-tolerant 'Gallionella capsiferriformans ES-2', in addition to known stalk formers such as Gallionella ferruginea and Gallionellaceae strain R-1. 26407813 9 59 theme Gallionella 1406:1416 arg1 ES-2 1436:1439 the putatively metal-tolerant 'Gallionella capsiferriformans ES-2' 1375:1440 the putatively metal-tolerant 'Gallionella capsiferriformans ES-2' 1375:1440 Classical 16S rRNA gene cloning showed that 96% of the Gallionella-related sequences had ≥ 97% identity to the putatively metal-tolerant 'Gallionella capsiferriformans ES-2', in addition to known stalk formers such as Gallionella ferruginea and Gallionellaceae strain R-1. 26407813 9 60 contain had 1353:1355 arg1 % 1314:1314 96% 1312:1314 96% of the Gallionella-related sequences 1312:1351 Classical 16S rRNA gene cloning showed that 96% of the Gallionella-related sequences had ≥ 97% identity to the putatively metal-tolerant 'Gallionella capsiferriformans ES-2', in addition to known stalk formers such as Gallionella ferruginea and Gallionellaceae strain R-1. 26407813 9 60 contain had 1353:1355 arg1 sequences 1343:1351 the Gallionella-related sequences 1319:1351 the Gallionella-related sequences 1319:1351 Classical 16S rRNA gene cloning showed that 96% of the Gallionella-related sequences had ≥ 97% identity to the putatively metal-tolerant 'Gallionella capsiferriformans ES-2', in addition to known stalk formers such as Gallionella ferruginea and Gallionellaceae strain R-1. 26407813 9 60 contain had 1353:1355 arg2 identity 1363:1370 ≥ 97% identity 1357:1370 ≥ 97% identity to the putatively metal-tolerant 'Gallionella capsiferriformans ES-2' 1357:1440 Classical 16S rRNA gene cloning showed that 96% of the Gallionella-related sequences had ≥ 97% identity to the putatively metal-tolerant 'Gallionella capsiferriformans ES-2', in addition to known stalk formers such as Gallionella ferruginea and Gallionellaceae strain R-1. 26407813 12 61 theme Cu 2004:2005 arg1 % 1984:1984 52-61% 1979:1984 52-61% of total sediment Cu 1979:2005 Sequential extraction of sediments suggested that Cu (52-61% of total sediment Cu) and other heavy metals were primarily bound to the iron oxide fractions. 26407813 12 61 theme Cu 2004:2005 arg1 Cu 2004:2005 total sediment Cu 1989:2005 total sediment Cu 1989:2005 Sequential extraction of sediments suggested that Cu (52-61% of total sediment Cu) and other heavy metals were primarily bound to the iron oxide fractions. 26407813 2 62 with groundwater 341:351 arg1 II 367:368 II 367:368 II 367:368 The transition from microoxic groundwater with ~5 mm Fe(II) to oxic surface water may provide a suitable habitat for microaerobic iron-oxidizing bacteria (FeOB). 26407813 2 62 with groundwater 341:351 arg1 Fe 364:365 ~5 mm Fe 358:365 ~5 mm Fe(II) 358:369 The transition from microoxic groundwater with ~5 mm Fe(II) to oxic surface water may provide a suitable habitat for microaerobic iron-oxidizing bacteria (FeOB). 26407813 4 63 theme metal 938:942 arg1 distribution 944:955 the metal distribution 934:955 the metal distribution in sediments 934:968 We (i) identified and quantified FeOB in water and sediment at the outflow, terraces, and creek, (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM), and (iii) examined the metal distribution in sediments. 26407813 0 64 with Dominance 0:8 arg1 stalks 95:100 Gallionella-like stalks 78:100 Gallionella-like stalks in metal-rich pH 6 mine water discharge 78:140 Dominance of 'Gallionella capsiferriformans' and heavy metal association with Gallionella-like stalks in metal-rich pH 6 mine water discharge. 26407813 5 65 theme study 1070:1074 arg1 period 1076:1081 a 6-month study period 1060:1081 a 6-month study period 1060:1081 Using quantitative PCR, a very high abundance of FeOB was demonstrated at all sites over a 6-month study period. 26407813 13 66 theme biogenic 2145:2152 arg1 oxides 2159:2164 biogenic iron oxides 2145:2164 biogenic iron oxides 2145:2164 These results show the importance of 'G. capsiferriformans' and biogenic iron oxides in slightly acidic but highly metal-contaminated freshwater environments. 26407813 2 67 theme ~5 358:359 arg1 mm 361:362 mm 361:362 mm 361:362 The transition from microoxic groundwater with ~5 mm Fe(II) to oxic surface water may provide a suitable habitat for microaerobic iron-oxidizing bacteria (FeOB). 26407813 4 68 from FeOB 648:651 arg1 sediment 666:673 sediment 666:673 sediment 666:673 We (i) identified and quantified FeOB in water and sediment at the outflow, terraces, and creek, (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM), and (iii) examined the metal distribution in sediments. 26407813 4 68 from FeOB 648:651 arg1 outflow 682:688 the outflow 678:688 the outflow 678:688 We (i) identified and quantified FeOB in water and sediment at the outflow, terraces, and creek, (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM), and (iii) examined the metal distribution in sediments. 26407813 4 68 from FeOB 648:651 arg1 water 656:660 water 656:660 water 656:660 We (i) identified and quantified FeOB in water and sediment at the outflow, terraces, and creek, (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM), and (iii) examined the metal distribution in sediments. 26407813 7 69 dep 88 1157:1158 arg1 to 1154:1155 to 1154:1155 to 1154:1155 clearly dominated the communities, accounting for up to 88% of Bacteria, with a minor contribution of other FeOB such as Sideroxydans spp. 26407813 10 70 theme Twisted 1541:1547 arg1 stalks 1549:1554 Twisted stalks 1541:1554 Twisted stalks from glass slides incubated in water and sediment 1541:1604 Twisted stalks from glass slides incubated in water and sediment were composed of the Fe(III) oxyhydroxide ferrihydrite, as well as polysaccharides. 26407813 9 71 theme known 1458:1462 arg1 formers 1470:1476 known stalk formers 1458:1476 known stalk formers such as Gallionella ferruginea and Gallionellaceae strain R-1 1458:1538 Classical 16S rRNA gene cloning showed that 96% of the Gallionella-related sequences had ≥ 97% identity to the putatively metal-tolerant 'Gallionella capsiferriformans ES-2', in addition to known stalk formers such as Gallionella ferruginea and Gallionellaceae strain R-1. 26407813 9 71 theme known 1458:1462 arg1 Gallionellaceae 1513:1527 Gallionellaceae 1513:1527 Gallionellaceae 1513:1527 Classical 16S rRNA gene cloning showed that 96% of the Gallionella-related sequences had ≥ 97% identity to the putatively metal-tolerant 'Gallionella capsiferriformans ES-2', in addition to known stalk formers such as Gallionella ferruginea and Gallionellaceae strain R-1. 26407813 9 71 theme known 1458:1462 arg1 ferruginea 1498:1507 ferruginea 1498:1507 ferruginea 1498:1507 Classical 16S rRNA gene cloning showed that 96% of the Gallionella-related sequences had ≥ 97% identity to the putatively metal-tolerant 'Gallionella capsiferriformans ES-2', in addition to known stalk formers such as Gallionella ferruginea and Gallionellaceae strain R-1. 26407813 13 72 theme acidic 2178:2183 arg1 environments 2226:2237 slightly acidic but highly metal-contaminated freshwater environments 2169:2237 slightly acidic but highly metal-contaminated freshwater environments 2169:2237 These results show the importance of 'G. capsiferriformans' and biogenic iron oxides in slightly acidic but highly metal-contaminated freshwater environments. 26407813 11 73 theme heavy 1831:1835 arg1 metals 1837:1842 heavy metals 1831:1842 heavy metals 1831:1842 SEM and scanning TEM-energy-dispersive X-ray spectroscopy revealed that stalk material contained Cu and Sn, demonstrating the association of heavy metals with biogenic iron oxides and the potential for metal retention by these stalks. 26407813 4 74 theme twisted 783:789 arg1 oxides 758:763 biogenic iron oxides 744:763 biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM) 744:912 We (i) identified and quantified FeOB in water and sediment at the outflow, terraces, and creek, (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM), and (iii) examined the metal distribution in sediments. 26407813 4 74 theme twisted 783:789 arg1 stalks 791:796 Gallionella-like twisted stalks 766:796 Gallionella-like twisted stalks 766:796 We (i) identified and quantified FeOB in water and sediment at the outflow, terraces, and creek, (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM), and (iii) examined the metal distribution in sediments. 26407813 9 75 theme Classical 1268:1276 arg1 rRNA 1282:1285 Classical 16S rRNA 1268:1285 Classical 16S rRNA gene cloning 1268:1298 Classical 16S rRNA gene cloning showed that 96% of the Gallionella-related sequences had ≥ 97% identity to the putatively metal-tolerant 'Gallionella capsiferriformans ES-2', in addition to known stalk formers such as Gallionella ferruginea and Gallionellaceae strain R-1. 26407813 1 76 theme pH 169:170 arg1 metal-contaminated 149:166 metal-contaminated 149:166 metal-contaminated 149:166 Heavy metal-contaminated, pH 6 mine water discharge created new streams and iron-rich terraces at a creek bank in a former uranium-mining area near Ronneburg, Germany. 26407813 1 76 theme pH 169:170 arg1 discharge 185:193 pH 6 mine water discharge 169:193 pH 6 mine water discharge 169:193 Heavy metal-contaminated, pH 6 mine water discharge created new streams and iron-rich terraces at a creek bank in a former uranium-mining area near Ronneburg, Germany. 26407813 2 77 theme suitable 407:414 arg1 habitat 416:422 a suitable habitat 405:422 a suitable habitat for microaerobic iron-oxidizing bacteria (FeOB) 405:470 The transition from microoxic groundwater with ~5 mm Fe(II) to oxic surface water may provide a suitable habitat for microaerobic iron-oxidizing bacteria (FeOB). 26407813 2 78 from groundwater 341:351 arg1 transition 315:324 The transition 311:324 The transition from microoxic groundwater with ~5 mm Fe(II) to oxic surface water 311:391 The transition from microoxic groundwater with ~5 mm Fe(II) to oxic surface water may provide a suitable habitat for microaerobic iron-oxidizing bacteria (FeOB). 26407813 11 79 theme iron 1858:1861 arg1 oxides 1863:1868 biogenic iron oxides 1849:1868 biogenic iron oxides 1849:1868 SEM and scanning TEM-energy-dispersive X-ray spectroscopy revealed that stalk material contained Cu and Sn, demonstrating the association of heavy metals with biogenic iron oxides and the potential for metal retention by these stalks. 26407813 1 80 theme mine 174:177 arg1 metal-contaminated 149:166 metal-contaminated 149:166 metal-contaminated 149:166 Heavy metal-contaminated, pH 6 mine water discharge created new streams and iron-rich terraces at a creek bank in a former uranium-mining area near Ronneburg, Germany. 26407813 1 80 theme mine 174:177 arg1 discharge 185:193 pH 6 mine water discharge 169:193 pH 6 mine water discharge 169:193 Heavy metal-contaminated, pH 6 mine water discharge created new streams and iron-rich terraces at a creek bank in a former uranium-mining area near Ronneburg, Germany. 26407813 4 81 theme iron 753:756 arg1 oxides 758:763 biogenic iron oxides 744:763 biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM) 744:912 We (i) identified and quantified FeOB in water and sediment at the outflow, terraces, and creek, (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM), and (iii) examined the metal distribution in sediments. 26407813 4 81 theme iron 753:756 arg1 stalks 791:796 Gallionella-like twisted stalks 766:796 Gallionella-like twisted stalks 766:796 We (i) identified and quantified FeOB in water and sediment at the outflow, terraces, and creek, (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM), and (iii) examined the metal distribution in sediments. 26407813 0 82 theme mine 121:124 arg1 discharge 132:140 metal-rich pH 6 mine water discharge 105:140 metal-rich pH 6 mine water discharge 105:140 Dominance of 'Gallionella capsiferriformans' and heavy metal association with Gallionella-like stalks in metal-rich pH 6 mine water discharge. 26407813 9 83 theme rRNA 1282:1285 arg1 cloning 1292:1298 Classical 16S rRNA gene cloning 1268:1298 Classical 16S rRNA gene cloning 1268:1298 Classical 16S rRNA gene cloning showed that 96% of the Gallionella-related sequences had ≥ 97% identity to the putatively metal-tolerant 'Gallionella capsiferriformans ES-2', in addition to known stalk formers such as Gallionella ferruginea and Gallionellaceae strain R-1. 26407813 4 84 theme transmission 817:828 arg1 SEM 851:853 SEM 851:853 SEM 851:853 We (i) identified and quantified FeOB in water and sediment at the outflow, terraces, and creek, (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM), and (iii) examined the metal distribution in sediments. 26407813 4 84 theme transmission 817:828 arg1 microscopy 839:848 scanning and transmission electron microscopy 804:848 microscopy 839:848 We (i) identified and quantified FeOB in water and sediment at the outflow, terraces, and creek, (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM), and (iii) examined the metal distribution in sediments. 26407813 7 85 theme Sideroxydans 1222:1233 arg1 spp 1235:1237 Sideroxydans spp 1222:1237 Sideroxydans spp 1222:1237 clearly dominated the communities, accounting for up to 88% of Bacteria, with a minor contribution of other FeOB such as Sideroxydans spp. 26407813 10 86 theme Fe 1627:1628 arg1 ferrihydrite 1648:1659 the Fe(III) oxyhydroxide ferrihydrite 1623:1659 the Fe(III) oxyhydroxide ferrihydrite 1623:1659 Twisted stalks from glass slides incubated in water and sediment were composed of the Fe(III) oxyhydroxide ferrihydrite, as well as polysaccharides. 26407813 9 87 theme 16S 1278:1280 arg1 rRNA 1282:1285 Classical 16S rRNA 1268:1285 Classical 16S rRNA gene cloning 1268:1298 Classical 16S rRNA gene cloning showed that 96% of the Gallionella-related sequences had ≥ 97% identity to the putatively metal-tolerant 'Gallionella capsiferriformans ES-2', in addition to known stalk formers such as Gallionella ferruginea and Gallionellaceae strain R-1. 26407813 1 88 theme new 203:205 arg1 streams 207:213 new streams 203:213 new streams 203:213 Heavy metal-contaminated, pH 6 mine water discharge created new streams and iron-rich terraces at a creek bank in a former uranium-mining area near Ronneburg, Germany. 26407813 12 89 theme Sequential 1925:1934 arg1 extraction 1936:1945 Sequential extraction 1925:1945 Sequential extraction of sediments 1925:1958 Sequential extraction of sediments suggested that Cu (52-61% of total sediment Cu) and other heavy metals were primarily bound to the iron oxide fractions. 26407813 1 90 from bank 249:252 arg1 area 281:284 a former uranium-mining area 257:284 a former uranium-mining area near Ronneburg, Germany 257:308 Heavy metal-contaminated, pH 6 mine water discharge created new streams and iron-rich terraces at a creek bank in a former uranium-mining area near Ronneburg, Germany. 26407813 7 91 theme other 1203:1207 arg1 FeOB 1209:1212 other FeOB 1203:1212 other FeOB 1203:1212 clearly dominated the communities, accounting for up to 88% of Bacteria, with a minor contribution of other FeOB such as Sideroxydans spp. 26407813 3 92 theme metal 567:571 arg1 retention 573:581 metal retention 567:581 metal retention 567:581 In this study, we investigated the potential contribution of these FeOB to iron oxidation and metal retention in this high-metal environment. 26407813 4 93 theme scanning 804:811 arg1 SEM 851:853 SEM 851:853 SEM 851:853 We (i) identified and quantified FeOB in water and sediment at the outflow, terraces, and creek, (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM), and (iii) examined the metal distribution in sediments. 26407813 4 93 theme scanning 804:811 arg1 microscopy 839:848 scanning and transmission electron microscopy 804:848 microscopy 839:848 We (i) identified and quantified FeOB in water and sediment at the outflow, terraces, and creek, (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM), and (iii) examined the metal distribution in sediments. 26407813 3 94 from contribution 518:529 arg1 environment 602:612 this high-metal environment 586:612 this high-metal environment 586:612 In this study, we investigated the potential contribution of these FeOB to iron oxidation and metal retention in this high-metal environment. 26407813 4 95 dep composition 729:739 arg1 ii 713:714 ii 713:714 ii 713:714 We (i) identified and quantified FeOB in water and sediment at the outflow, terraces, and creek, (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM), and (iii) examined the metal distribution in sediments. 26407813 0 96 theme Gallionella-like 78:93 arg1 stalks 95:100 Gallionella-like stalks 78:100 Gallionella-like stalks in metal-rich pH 6 mine water discharge 78:140 Dominance of 'Gallionella capsiferriformans' and heavy metal association with Gallionella-like stalks in metal-rich pH 6 mine water discharge. 26407813 4 97 from creek 705:709 arg1 sediment 666:673 sediment 666:673 sediment 666:673 We (i) identified and quantified FeOB in water and sediment at the outflow, terraces, and creek, (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM), and (iii) examined the metal distribution in sediments. 26407813 4 97 from creek 705:709 arg1 outflow 682:688 the outflow 678:688 the outflow 678:688 We (i) identified and quantified FeOB in water and sediment at the outflow, terraces, and creek, (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM), and (iii) examined the metal distribution in sediments. 26407813 4 97 from creek 705:709 arg1 water 656:660 water 656:660 water 656:660 We (i) identified and quantified FeOB in water and sediment at the outflow, terraces, and creek, (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM), and (iii) examined the metal distribution in sediments. 26407813 9 98 theme sequences 1343:1351 arg1 % 1314:1314 96% 1312:1314 96% of the Gallionella-related sequences 1312:1351 Classical 16S rRNA gene cloning showed that 96% of the Gallionella-related sequences had ≥ 97% identity to the putatively metal-tolerant 'Gallionella capsiferriformans ES-2', in addition to known stalk formers such as Gallionella ferruginea and Gallionellaceae strain R-1. 26407813 9 98 theme sequences 1343:1351 arg1 sequences 1343:1351 the Gallionella-related sequences 1319:1351 the Gallionella-related sequences 1319:1351 Classical 16S rRNA gene cloning showed that 96% of the Gallionella-related sequences had ≥ 97% identity to the putatively metal-tolerant 'Gallionella capsiferriformans ES-2', in addition to known stalk formers such as Gallionella ferruginea and Gallionellaceae strain R-1. 26407813 2 99 theme iron-oxidizing 441:454 arg1 FeOB 466:469 FeOB 466:469 FeOB 466:469 The transition from microoxic groundwater with ~5 mm Fe(II) to oxic surface water may provide a suitable habitat for microaerobic iron-oxidizing bacteria (FeOB). 26407813 2 99 theme iron-oxidizing 441:454 arg1 bacteria 456:463 microaerobic iron-oxidizing bacteria 428:463 microaerobic iron-oxidizing bacteria (FeOB) 428:470 The transition from microoxic groundwater with ~5 mm Fe(II) to oxic surface water may provide a suitable habitat for microaerobic iron-oxidizing bacteria (FeOB). 26407813 9 100 theme ≥ 1357:1357 arg1 % 1361:1361 % 1361:1361 % 1361:1361 Classical 16S rRNA gene cloning showed that 96% of the Gallionella-related sequences had ≥ 97% identity to the putatively metal-tolerant 'Gallionella capsiferriformans ES-2', in addition to known stalk formers such as Gallionella ferruginea and Gallionellaceae strain R-1. 26407813 11 101 theme biogenic 1849:1856 arg1 oxides 1863:1868 biogenic iron oxides 1849:1868 biogenic iron oxides 1849:1868 SEM and scanning TEM-energy-dispersive X-ray spectroscopy revealed that stalk material contained Cu and Sn, demonstrating the association of heavy metals with biogenic iron oxides and the potential for metal retention by these stalks. 26407813 0 102 theme pH 116:117 arg1 discharge 132:140 metal-rich pH 6 mine water discharge 105:140 metal-rich pH 6 mine water discharge 105:140 Dominance of 'Gallionella capsiferriformans' and heavy metal association with Gallionella-like stalks in metal-rich pH 6 mine water discharge. 26407813 4 103 dep identified 622:631 arg1 i 619:619 i 619:619 i 619:619 We (i) identified and quantified FeOB in water and sediment at the outflow, terraces, and creek, (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM), and (iii) examined the metal distribution in sediments. 26407813 7 104 theme Bacteria 1164:1171 arg1 Bacteria 1164:1171 Bacteria 1164:1171 Bacteria 1164:1171 clearly dominated the communities, accounting for up to 88% of Bacteria, with a minor contribution of other FeOB such as Sideroxydans spp. 26407813 7 104 theme Bacteria 1164:1171 arg1 % 1159:1159 up to 88% 1151:1159 up to 88% of Bacteria 1151:1171 clearly dominated the communities, accounting for up to 88% of Bacteria, with a minor contribution of other FeOB such as Sideroxydans spp. 26407813 12 105 theme oxide 2064:2068 arg1 fractions 2070:2078 the iron oxide fractions 2055:2078 the iron oxide fractions 2055:2078 Sequential extraction of sediments suggested that Cu (52-61% of total sediment Cu) and other heavy metals were primarily bound to the iron oxide fractions. 26407813 11 106 theme X-ray 1729:1733 arg1 spectroscopy 1735:1746 SEM and scanning TEM-energy-dispersive X-ray spectroscopy 1690:1746 spectroscopy 1735:1746 SEM and scanning TEM-energy-dispersive X-ray spectroscopy revealed that stalk material contained Cu and Sn, demonstrating the association of heavy metals with biogenic iron oxides and the potential for metal retention by these stalks. 26407813 5 107 theme quantitative 977:988 arg1 PCR 990:992 quantitative PCR 977:992 quantitative PCR 977:992 Using quantitative PCR, a very high abundance of FeOB was demonstrated at all sites over a 6-month study period. 26407813 2 108 theme mm 361:362 arg1 II 367:368 II 367:368 II 367:368 The transition from microoxic groundwater with ~5 mm Fe(II) to oxic surface water may provide a suitable habitat for microaerobic iron-oxidizing bacteria (FeOB). 26407813 2 108 theme mm 361:362 arg1 Fe 364:365 ~5 mm Fe 358:365 ~5 mm Fe(II) 358:369 The transition from microoxic groundwater with ~5 mm Fe(II) to oxic surface water may provide a suitable habitat for microaerobic iron-oxidizing bacteria (FeOB). 26407813 0 109 theme Gallionella 14:24 arg1 capsiferriformans 26:42 Gallionella capsiferriformans 14:42 'Gallionella capsiferriformans' 13:43 Dominance of 'Gallionella capsiferriformans' and heavy metal association with Gallionella-like stalks in metal-rich pH 6 mine water discharge. 26407813 1 110 theme former 259:264 arg1 area 281:284 a former uranium-mining area 257:284 a former uranium-mining area near Ronneburg, Germany 257:308 Heavy metal-contaminated, pH 6 mine water discharge created new streams and iron-rich terraces at a creek bank in a former uranium-mining area near Ronneburg, Germany. 26407813 13 111 theme freshwater 2215:2224 arg1 environments 2226:2237 slightly acidic but highly metal-contaminated freshwater environments 2169:2237 slightly acidic but highly metal-contaminated freshwater environments 2169:2237 These results show the importance of 'G. capsiferriformans' and biogenic iron oxides in slightly acidic but highly metal-contaminated freshwater environments. 26407813 9 112 theme % 1361:1361 arg1 identity 1363:1370 ≥ 97% identity 1357:1370 ≥ 97% identity to the putatively metal-tolerant 'Gallionella capsiferriformans ES-2' 1357:1440 Classical 16S rRNA gene cloning showed that 96% of the Gallionella-related sequences had ≥ 97% identity to the putatively metal-tolerant 'Gallionella capsiferriformans ES-2', in addition to known stalk formers such as Gallionella ferruginea and Gallionellaceae strain R-1. 26407813 3 113 theme high-metal 591:600 arg1 environment 602:612 this high-metal environment 586:612 this high-metal environment 586:612 In this study, we investigated the potential contribution of these FeOB to iron oxidation and metal retention in this high-metal environment. 26407813 12 114 theme other 2012:2016 arg1 metals 2024:2029 other heavy metals 2012:2029 other heavy metals 2012:2029 Sequential extraction of sediments suggested that Cu (52-61% of total sediment Cu) and other heavy metals were primarily bound to the iron oxide fractions. 26407813 2 115 theme oxic 374:377 arg1 water 387:391 oxic surface water 374:391 oxic surface water 374:391 The transition from microoxic groundwater with ~5 mm Fe(II) to oxic surface water may provide a suitable habitat for microaerobic iron-oxidizing bacteria (FeOB). 26407813 11 116 with association 1816:1826 arg1 potential 1878:1886 the potential 1874:1886 the potential for metal retention by these stalks 1874:1922 SEM and scanning TEM-energy-dispersive X-ray spectroscopy revealed that stalk material contained Cu and Sn, demonstrating the association of heavy metals with biogenic iron oxides and the potential for metal retention by these stalks. 26407813 11 116 with association 1816:1826 arg1 oxides 1863:1868 biogenic iron oxides 1849:1868 biogenic iron oxides 1849:1868 SEM and scanning TEM-energy-dispersive X-ray spectroscopy revealed that stalk material contained Cu and Sn, demonstrating the association of heavy metals with biogenic iron oxides and the potential for metal retention by these stalks. 26407813 4 117 theme laser 881:885 arg1 microscopy 896:905 confocal laser scanning microscopy 872:905 scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM) 804:912 We (i) identified and quantified FeOB in water and sediment at the outflow, terraces, and creek, (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM), and (iii) examined the metal distribution in sediments. 26407813 4 117 theme laser 881:885 arg1 CLSM 908:911 CLSM 908:911 CLSM 908:911 We (i) identified and quantified FeOB in water and sediment at the outflow, terraces, and creek, (ii) studied the composition of biogenic iron oxides (Gallionella-like twisted stalks) with scanning and transmission electron microscopy (SEM, TEM) as well as confocal laser scanning microscopy (CLSM), and (iii) examined the metal distribution in sediments. 26407813 13 118 from importance 2104:2113 arg1 environments 2226:2237 slightly acidic but highly metal-contaminated freshwater environments 2169:2237 slightly acidic but highly metal-contaminated freshwater environments 2169:2237 These results show the importance of 'G. capsiferriformans' and biogenic iron oxides in slightly acidic but highly metal-contaminated freshwater environments. 26407813 0 119 theme heavy 49:53 arg1 association 61:71 heavy metal association 49:71 heavy metal association with Gallionella-like stalks in metal-rich pH 6 mine water discharge 49:140 Dominance of 'Gallionella capsiferriformans' and heavy metal association with Gallionella-like stalks in metal-rich pH 6 mine water discharge. 26407813 13 120 theme oxides 2159:2164 arg1 importance 2104:2113 the importance 2100:2113 the importance of 'G. capsiferriformans' and biogenic iron oxides in slightly acidic but highly metal-contaminated freshwater environments 2100:2237 These results show the importance of 'G. capsiferriformans' and biogenic iron oxides in slightly acidic but highly metal-contaminated freshwater environments. 26407813 9 121 theme capsiferriformans 1418:1434 arg1 ES-2 1436:1439 the putatively metal-tolerant 'Gallionella capsiferriformans ES-2' 1375:1440 the putatively metal-tolerant 'Gallionella capsiferriformans ES-2' 1375:1440 Classical 16S rRNA gene cloning showed that 96% of the Gallionella-related sequences had ≥ 97% identity to the putatively metal-tolerant 'Gallionella capsiferriformans ES-2', in addition to known stalk formers such as Gallionella ferruginea and Gallionellaceae strain R-1. 26407813 0 122 theme water 126:130 arg1 discharge 132:140 metal-rich pH 6 mine water discharge 105:140 metal-rich pH 6 mine water discharge 105:140 Dominance of 'Gallionella capsiferriformans' and heavy metal association with Gallionella-like stalks in metal-rich pH 6 mine water discharge. 26407813 12 123 theme sediment 1995:2002 arg1 Cu 2004:2005 total sediment Cu 1989:2005 total sediment Cu 1989:2005 Sequential extraction of sediments suggested that Cu (52-61% of total sediment Cu) and other heavy metals were primarily bound to the iron oxide fractions. 26407813 5 124 theme FeOB 1020:1023 arg1 abundance 1007:1015 a very high abundance 995:1015 a very high abundance of FeOB 995:1023 Using quantitative PCR, a very high abundance of FeOB was demonstrated at all sites over a 6-month study period. 26407813 1 125 theme iron-rich 219:227 arg1 terraces 229:236 iron-rich terraces 219:236 iron-rich terraces 219:236 Heavy metal-contaminated, pH 6 mine water discharge created new streams and iron-rich terraces at a creek bank in a former uranium-mining area near Ronneburg, Germany. 26407813 13 126 theme iron 2154:2157 arg1 oxides 2159:2164 biogenic iron oxides 2145:2164 biogenic iron oxides 2145:2164 These results show the importance of 'G. capsiferriformans' and biogenic iron oxides in slightly acidic but highly metal-contaminated freshwater environments. 26407813 8 127 theme Ferrovum 1245:1252 arg1 myxofaciens 1254:1264 Ferrovum myxofaciens 1245:1264 Ferrovum myxofaciens 1245:1264 and 'Ferrovum myxofaciens'. 26407813 11 128 theme SEM 1690:1692 arg1 spectroscopy 1735:1746 SEM and scanning TEM-energy-dispersive X-ray spectroscopy 1690:1746 spectroscopy 1735:1746 SEM and scanning TEM-energy-dispersive X-ray spectroscopy revealed that stalk material contained Cu and Sn, demonstrating the association of heavy metals with biogenic iron oxides and the potential for metal retention by these stalks. 25636842 5 0 dep biofouling 780:789 arg1 rise 801:804 pressure rise 792:804 pressure rise over a given period 792:824 The addition of 40 μM PROLI NONOate at 24-h intervals to a laboratory-scale RO system led to a 92% reduction in the rate of biofouling (pressure rise over a given period) by a bacterial community cultured from an industrial RO membrane. 25636842 8 1 theme transmembrane 1452:1464 arg1 TMP 1476:1478 TMP 1476:1478 TMP 1476:1478 The addition of PROLI NONOate led to a 22% increase in the time required for the RO module to reach its maximum transmembrane pressure (TMP), further indicating that NO treatment delayed fouling. 25636842 8 1 theme transmembrane 1452:1464 arg1 pressure 1466:1473 its maximum transmembrane pressure 1440:1473 its maximum transmembrane pressure (TMP) 1440:1479 The addition of PROLI NONOate led to a 22% increase in the time required for the RO module to reach its maximum transmembrane pressure (TMP), further indicating that NO treatment delayed fouling. 25636842 10 2 theme NONOate 1747:1753 arg1 application 1726:1736 the application 1722:1736 the application of PROLI NONOate for prevention of RO biofouling 1722:1785 These results present strong evidence for the application of PROLI NONOate for prevention of RO biofouling. 25636842 2 3 theme industrial 333:342 arg1 bioreactor 353:362 industrial membrane bioreactor 333:362 industrial membrane bioreactor 333:362 This study investigated the dispersal potential of the nitric oxide (NO) donor compound, PROLI NONOate, on single- and mixed-species biofilms formed by bacteria isolated from industrial membrane bioreactor and reverse osmosis (RO) membranes. 25636842 6 4 theme microbial 1102:1110 arg1 cells 1112:1116 microbial cells 1102:1116 microbial cells 1102:1116 Confocal microscopy and extracellular polymeric substances (EPS) extraction revealed that PROLI NONOate treatment led to a 48% reduction in polysaccharides, a 66% reduction in proteins, and a 29% reduction in microbial cells compared to the untreated control. 25636842 8 5 from increase 1383:1390 arg1 time 1399:1402 the time 1395:1402 the time required for the RO module to reach its maximum transmembrane pressure (TMP) 1395:1479 The addition of PROLI NONOate led to a 22% increase in the time required for the RO module to reach its maximum transmembrane pressure (TMP), further indicating that NO treatment delayed fouling. 25636842 10 6 theme RO 1773:1774 arg1 biofouling 1776:1785 RO biofouling 1773:1785 RO biofouling 1773:1785 These results present strong evidence for the application of PROLI NONOate for prevention of RO biofouling. 25636842 6 7 theme 29 1085:1086 arg1 % 1087:1087 % 1087:1087 % 1087:1087 Confocal microscopy and extracellular polymeric substances (EPS) extraction revealed that PROLI NONOate treatment led to a 48% reduction in polysaccharides, a 66% reduction in proteins, and a 29% reduction in microbial cells compared to the untreated control. 25636842 6 8 theme polymeric 931:939 arg1 EPS 953:955 EPS 953:955 EPS 953:955 Confocal microscopy and extracellular polymeric substances (EPS) extraction revealed that PROLI NONOate treatment led to a 48% reduction in polysaccharides, a 66% reduction in proteins, and a 29% reduction in microbial cells compared to the untreated control. 25636842 6 8 theme polymeric 931:939 arg1 substances 941:950 extracellular polymeric substances 917:950 extracellular polymeric substances (EPS) 917:956 Confocal microscopy and extracellular polymeric substances (EPS) extraction revealed that PROLI NONOate treatment led to a 48% reduction in polysaccharides, a 66% reduction in proteins, and a 29% reduction in microbial cells compared to the untreated control. 25636842 4 9 theme dispersed 622:630 arg1 biofilms 646:653 successfully dispersed mixed-species biofilms 609:653 successfully dispersed mixed-species biofilms 609:653 Confocal microscopy revealed that PROLI NONOate exposure induced biofilm dispersal in all but two of the bacteria tested and successfully dispersed mixed-species biofilms. 25636842 5 10 theme 24-h 695:698 arg1 intervals 700:708 24-h intervals 695:708 24-h intervals 695:708 The addition of 40 μM PROLI NONOate at 24-h intervals to a laboratory-scale RO system led to a 92% reduction in the rate of biofouling (pressure rise over a given period) by a bacterial community cultured from an industrial RO membrane. 25636842 6 11 theme Confocal 893:900 arg1 microscopy 902:911 Confocal microscopy 893:911 Confocal microscopy 893:911 Confocal microscopy and extracellular polymeric substances (EPS) extraction revealed that PROLI NONOate treatment led to a 48% reduction in polysaccharides, a 66% reduction in proteins, and a 29% reduction in microbial cells compared to the untreated control. 25636842 6 12 theme 66 1052:1053 arg1 % 1054:1054 % 1054:1054 % 1054:1054 Confocal microscopy and extracellular polymeric substances (EPS) extraction revealed that PROLI NONOate treatment led to a 48% reduction in polysaccharides, a 66% reduction in proteins, and a 29% reduction in microbial cells compared to the untreated control. 25636842 5 13 theme μM 675:676 arg1 NONOate 684:690 40 μM PROLI NONOate 672:690 40 μM PROLI NONOate 672:690 The addition of 40 μM PROLI NONOate at 24-h intervals to a laboratory-scale RO system led to a 92% reduction in the rate of biofouling (pressure rise over a given period) by a bacterial community cultured from an industrial RO membrane. 25636842 2 14 theme oxide 220:224 arg1 potential 196:204 the dispersal potential 182:204 the dispersal potential of the nitric oxide (NO) donor compound, PROLI NONOate, on single- and mixed-species biofilms formed by bacteria isolated from industrial membrane bioreactor and reverse osmosis (RO) membranes 182:397 This study investigated the dispersal potential of the nitric oxide (NO) donor compound, PROLI NONOate, on single- and mixed-species biofilms formed by bacteria isolated from industrial membrane bioreactor and reverse osmosis (RO) membranes. 25636842 5 15 theme NONOate 684:690 arg1 addition 660:667 The addition 656:667 The addition of 40 μM PROLI NONOate at 24-h intervals to a laboratory-scale RO system 656:740 The addition of 40 μM PROLI NONOate at 24-h intervals to a laboratory-scale RO system led to a 92% reduction in the rate of biofouling (pressure rise over a given period) by a bacterial community cultured from an industrial RO membrane. 25636842 5 16 theme RO 880:881 arg1 membrane 883:890 an industrial RO membrane 866:890 an industrial RO membrane 866:890 The addition of 40 μM PROLI NONOate at 24-h intervals to a laboratory-scale RO system led to a 92% reduction in the rate of biofouling (pressure rise over a given period) by a bacterial community cultured from an industrial RO membrane. 25636842 6 17 theme PROLI 983:987 arg1 treatment 997:1005 PROLI NONOate treatment 983:1005 PROLI NONOate treatment 983:1005 Confocal microscopy and extracellular polymeric substances (EPS) extraction revealed that PROLI NONOate treatment led to a 48% reduction in polysaccharides, a 66% reduction in proteins, and a 29% reduction in microbial cells compared to the untreated control. 25636842 9 18 theme NO 1578:1579 arg1 treatment 1581:1589 the NO treatment 1574:1589 the NO treatment 1574:1589 Pyrosequencing analysis revealed that the NO treatment did not significantly alter the microbial community composition of the membrane biofilm. 25636842 0 19 theme osmosis 50:56 arg1 biofouling 67:76 reverse osmosis membrane biofouling 42:76 reverse osmosis membrane biofouling 42:76 Nitric oxide treatment for the control of reverse osmosis membrane biofouling. 25636842 2 20 theme donor 231:235 arg1 compound 237:244 donor compound 231:244 the nitric oxide (NO) donor compound 209:244 This study investigated the dispersal potential of the nitric oxide (NO) donor compound, PROLI NONOate, on single- and mixed-species biofilms formed by bacteria isolated from industrial membrane bioreactor and reverse osmosis (RO) membranes. 25636842 5 21 theme bacterial 832:840 arg1 community 842:850 a bacterial community 830:850 a bacterial community cultured from an industrial RO membrane 830:890 The addition of 40 μM PROLI NONOate at 24-h intervals to a laboratory-scale RO system led to a 92% reduction in the rate of biofouling (pressure rise over a given period) by a bacterial community cultured from an industrial RO membrane. 25636842 0 22 theme biofouling 67:76 arg1 control 31:37 the control 27:37 the control of reverse osmosis membrane biofouling 27:76 Nitric oxide treatment for the control of reverse osmosis membrane biofouling. 25636842 8 23 theme NONOate 1362:1368 arg1 addition 1344:1351 The addition 1340:1351 The addition of PROLI NONOate 1340:1368 The addition of PROLI NONOate led to a 22% increase in the time required for the RO module to reach its maximum transmembrane pressure (TMP), further indicating that NO treatment delayed fouling. 25636842 5 24 theme laboratory-scale 715:730 arg1 system 735:740 a laboratory-scale RO system 713:740 a laboratory-scale RO system 713:740 The addition of 40 μM PROLI NONOate at 24-h intervals to a laboratory-scale RO system led to a 92% reduction in the rate of biofouling (pressure rise over a given period) by a bacterial community cultured from an industrial RO membrane. 25636842 1 25 theme water 133:137 arg1 systems 149:155 membrane-based water treatment systems 118:155 membrane-based water treatment systems 118:155 Biofouling remains a key challenge for membrane-based water treatment systems. 25636842 3 26 theme PROLI 417:421 arg1 NONOate 423:429 PROLI NONOate 417:429 PROLI NONOate 417:429 The potential of PROLI NONOate to control RO membrane biofouling was also examined. 25636842 7 27 dep % 1196:1196 arg1 compared 1198:1205 compared 1198:1205 compared to 98% 1198:1212 A reduction in biofilm surface coverage (59% compared to 98%, treated compared to control) and average thickness (20 μm compared to 26 μm, treated compared to control) was also observed. 25636842 9 28 theme community 1633:1641 arg1 composition 1643:1653 the microbial community composition 1619:1653 the microbial community composition of the membrane biofilm 1619:1677 Pyrosequencing analysis revealed that the NO treatment did not significantly alter the microbial community composition of the membrane biofilm. 25636842 8 29 theme 22 1379:1380 arg1 % 1381:1381 % 1381:1381 % 1381:1381 The addition of PROLI NONOate led to a 22% increase in the time required for the RO module to reach its maximum transmembrane pressure (TMP), further indicating that NO treatment delayed fouling. 25636842 2 30 theme osmosis 376:382 arg1 membranes 389:397 industrial membrane bioreactor and reverse osmosis (RO) membranes 333:397 industrial membrane bioreactor and reverse osmosis (RO) membranes 333:397 This study investigated the dispersal potential of the nitric oxide (NO) donor compound, PROLI NONOate, on single- and mixed-species biofilms formed by bacteria isolated from industrial membrane bioreactor and reverse osmosis (RO) membranes. 25636842 0 31 theme Nitric 0:5 arg1 oxide 7:11 Nitric oxide 0:11 Nitric oxide 0:11 Nitric oxide treatment for the control of reverse osmosis membrane biofouling. 25636842 6 32 theme 48 1016:1017 arg1 % 1018:1018 % 1018:1018 % 1018:1018 Confocal microscopy and extracellular polymeric substances (EPS) extraction revealed that PROLI NONOate treatment led to a 48% reduction in polysaccharides, a 66% reduction in proteins, and a 29% reduction in microbial cells compared to the untreated control. 25636842 3 33 theme RO 442:443 arg1 biofouling 454:463 control RO membrane biofouling 434:463 control RO membrane biofouling 434:463 The potential of PROLI NONOate to control RO membrane biofouling was also examined. 25636842 1 34 theme key 100:102 arg1 challenge 104:112 a key challenge 98:112 a key challenge for membrane-based water treatment systems 98:155 Biofouling remains a key challenge for membrane-based water treatment systems. 25636842 9 35 theme membrane 1662:1669 arg1 biofilm 1671:1677 the membrane biofilm 1658:1677 the membrane biofilm 1658:1677 Pyrosequencing analysis revealed that the NO treatment did not significantly alter the microbial community composition of the membrane biofilm. 25636842 10 36 theme strong 1702:1707 arg1 evidence 1709:1716 strong evidence 1702:1716 strong evidence for the application of PROLI NONOate for prevention of RO biofouling 1702:1785 These results present strong evidence for the application of PROLI NONOate for prevention of RO biofouling. 25636842 7 37 dep thickness 1256:1264 arg1 μm 1270:1271 20 μm 1267:1271 20 μm compared to 26 μm, treated compared to control 1267:1318 A reduction in biofilm surface coverage (59% compared to 98%, treated compared to control) and average thickness (20 μm compared to 26 μm, treated compared to control) was also observed. 25636842 4 38 theme Confocal 484:491 arg1 microscopy 493:502 Confocal microscopy 484:502 Confocal microscopy 484:502 Confocal microscopy revealed that PROLI NONOate exposure induced biofilm dispersal in all but two of the bacteria tested and successfully dispersed mixed-species biofilms. 25636842 4 39 theme NONOate 524:530 arg1 exposure 532:539 PROLI NONOate exposure 518:539 PROLI NONOate exposure 518:539 Confocal microscopy revealed that PROLI NONOate exposure induced biofilm dispersal in all but two of the bacteria tested and successfully dispersed mixed-species biofilms. 25636842 6 40 theme % 1054:1054 arg1 reduction 1056:1064 a 66% reduction 1050:1064 a 66% reduction in proteins 1050:1076 Confocal microscopy and extracellular polymeric substances (EPS) extraction revealed that PROLI NONOate treatment led to a 48% reduction in polysaccharides, a 66% reduction in proteins, and a 29% reduction in microbial cells compared to the untreated control. 25636842 7 41 theme surface 1176:1182 arg1 coverage 1184:1191 biofilm surface coverage 1168:1191 biofilm surface coverage (59% compared to 98%, treated compared to control) 1168:1242 A reduction in biofilm surface coverage (59% compared to 98%, treated compared to control) and average thickness (20 μm compared to 26 μm, treated compared to control) was also observed. 25636842 2 42 theme membrane 344:351 arg1 bioreactor 353:362 industrial membrane bioreactor 333:362 industrial membrane bioreactor 333:362 This study investigated the dispersal potential of the nitric oxide (NO) donor compound, PROLI NONOate, on single- and mixed-species biofilms formed by bacteria isolated from industrial membrane bioreactor and reverse osmosis (RO) membranes. 25636842 5 43 from intervals 700:708 arg1 addition 660:667 The addition 656:667 The addition of 40 μM PROLI NONOate at 24-h intervals to a laboratory-scale RO system 656:740 The addition of 40 μM PROLI NONOate at 24-h intervals to a laboratory-scale RO system led to a 92% reduction in the rate of biofouling (pressure rise over a given period) by a bacterial community cultured from an industrial RO membrane. 25636842 7 44 from reduction 1155:1163 arg1 thickness 1256:1264 average thickness 1248:1264 average thickness (20 μm compared to 26 μm, treated compared to control) 1248:1319 A reduction in biofilm surface coverage (59% compared to 98%, treated compared to control) and average thickness (20 μm compared to 26 μm, treated compared to control) was also observed. 25636842 7 44 from reduction 1155:1163 arg1 coverage 1184:1191 biofilm surface coverage 1168:1191 biofilm surface coverage (59% compared to 98%, treated compared to control) 1168:1242 A reduction in biofilm surface coverage (59% compared to 98%, treated compared to control) and average thickness (20 μm compared to 26 μm, treated compared to control) was also observed. 25636842 8 45 theme maximum 1444:1450 arg1 TMP 1476:1478 TMP 1476:1478 TMP 1476:1478 The addition of PROLI NONOate led to a 22% increase in the time required for the RO module to reach its maximum transmembrane pressure (TMP), further indicating that NO treatment delayed fouling. 25636842 8 45 theme maximum 1444:1450 arg1 pressure 1466:1473 its maximum transmembrane pressure 1440:1473 its maximum transmembrane pressure (TMP) 1440:1479 The addition of PROLI NONOate led to a 22% increase in the time required for the RO module to reach its maximum transmembrane pressure (TMP), further indicating that NO treatment delayed fouling. 25636842 10 46 theme PROLI 1741:1745 arg1 NONOate 1747:1753 PROLI NONOate 1741:1753 PROLI NONOate 1741:1753 These results present strong evidence for the application of PROLI NONOate for prevention of RO biofouling. 25636842 2 47 theme single- 265:271 arg1 biofilms 291:298 single- and mixed-species biofilms 265:298 single- and mixed-species biofilms formed by bacteria isolated from industrial membrane bioreactor and reverse osmosis (RO) membranes 265:397 This study investigated the dispersal potential of the nitric oxide (NO) donor compound, PROLI NONOate, on single- and mixed-species biofilms formed by bacteria isolated from industrial membrane bioreactor and reverse osmosis (RO) membranes. 25636842 2 48 from potential 196:204 arg1 biofilms 291:298 single- and mixed-species biofilms 265:298 single- and mixed-species biofilms formed by bacteria isolated from industrial membrane bioreactor and reverse osmosis (RO) membranes 265:397 This study investigated the dispersal potential of the nitric oxide (NO) donor compound, PROLI NONOate, on single- and mixed-species biofilms formed by bacteria isolated from industrial membrane bioreactor and reverse osmosis (RO) membranes. 25636842 2 49 attach isolated 319:326 arg1 membranes 389:397 industrial membrane bioreactor and reverse osmosis (RO) membranes 333:397 industrial membrane bioreactor and reverse osmosis (RO) membranes 333:397 This study investigated the dispersal potential of the nitric oxide (NO) donor compound, PROLI NONOate, on single- and mixed-species biofilms formed by bacteria isolated from industrial membrane bioreactor and reverse osmosis (RO) membranes. 25636842 2 49 attach isolated 319:326 arg2 bacteria 310:317 bacteria 310:317 bacteria isolated from industrial membrane bioreactor and reverse osmosis (RO) membranes 310:397 This study investigated the dispersal potential of the nitric oxide (NO) donor compound, PROLI NONOate, on single- and mixed-species biofilms formed by bacteria isolated from industrial membrane bioreactor and reverse osmosis (RO) membranes. 25636842 10 50 theme biofouling 1776:1785 arg1 prevention 1759:1768 prevention 1759:1768 prevention of RO biofouling 1759:1785 These results present strong evidence for the application of PROLI NONOate for prevention of RO biofouling. 25636842 6 51 from reduction 1020:1028 arg1 polysaccharides 1033:1047 polysaccharides 1033:1047 polysaccharides 1033:1047 Confocal microscopy and extracellular polymeric substances (EPS) extraction revealed that PROLI NONOate treatment led to a 48% reduction in polysaccharides, a 66% reduction in proteins, and a 29% reduction in microbial cells compared to the untreated control. 25636842 6 51 from reduction 1020:1028 arg1 cells 1112:1116 microbial cells 1102:1116 microbial cells 1102:1116 Confocal microscopy and extracellular polymeric substances (EPS) extraction revealed that PROLI NONOate treatment led to a 48% reduction in polysaccharides, a 66% reduction in proteins, and a 29% reduction in microbial cells compared to the untreated control. 25636842 6 51 from reduction 1020:1028 arg1 proteins 1069:1076 proteins 1069:1076 proteins 1069:1076 Confocal microscopy and extracellular polymeric substances (EPS) extraction revealed that PROLI NONOate treatment led to a 48% reduction in polysaccharides, a 66% reduction in proteins, and a 29% reduction in microbial cells compared to the untreated control. 25636842 5 52 theme given 813:817 arg1 period 819:824 a given period 811:824 a given period 811:824 The addition of 40 μM PROLI NONOate at 24-h intervals to a laboratory-scale RO system led to a 92% reduction in the rate of biofouling (pressure rise over a given period) by a bacterial community cultured from an industrial RO membrane. 25636842 6 53 theme % 1087:1087 arg1 reduction 1089:1097 a 29% reduction 1083:1097 a 29% reduction in microbial cells 1083:1116 Confocal microscopy and extracellular polymeric substances (EPS) extraction revealed that PROLI NONOate treatment led to a 48% reduction in polysaccharides, a 66% reduction in proteins, and a 29% reduction in microbial cells compared to the untreated control. 25636842 2 54 theme mixed-species 277:289 arg1 biofilms 291:298 single- and mixed-species biofilms 265:298 single- and mixed-species biofilms formed by bacteria isolated from industrial membrane bioreactor and reverse osmosis (RO) membranes 265:397 This study investigated the dispersal potential of the nitric oxide (NO) donor compound, PROLI NONOate, on single- and mixed-species biofilms formed by bacteria isolated from industrial membrane bioreactor and reverse osmosis (RO) membranes. 25636842 5 55 theme pressure 792:799 arg1 rise 801:804 pressure rise 792:804 pressure rise over a given period 792:824 The addition of 40 μM PROLI NONOate at 24-h intervals to a laboratory-scale RO system led to a 92% reduction in the rate of biofouling (pressure rise over a given period) by a bacterial community cultured from an industrial RO membrane. 25636842 6 56 theme extracellular 917:929 arg1 EPS 953:955 EPS 953:955 EPS 953:955 Confocal microscopy and extracellular polymeric substances (EPS) extraction revealed that PROLI NONOate treatment led to a 48% reduction in polysaccharides, a 66% reduction in proteins, and a 29% reduction in microbial cells compared to the untreated control. 25636842 6 56 theme extracellular 917:929 arg1 substances 941:950 extracellular polymeric substances 917:950 extracellular polymeric substances (EPS) 917:956 Confocal microscopy and extracellular polymeric substances (EPS) extraction revealed that PROLI NONOate treatment led to a 48% reduction in polysaccharides, a 66% reduction in proteins, and a 29% reduction in microbial cells compared to the untreated control. 25636842 2 57 dep oxide 220:224 arg1 compound 237:244 donor compound 231:244 the nitric oxide (NO) donor compound 209:244 This study investigated the dispersal potential of the nitric oxide (NO) donor compound, PROLI NONOate, on single- and mixed-species biofilms formed by bacteria isolated from industrial membrane bioreactor and reverse osmosis (RO) membranes. 25636842 9 58 theme Pyrosequencing 1536:1549 arg1 analysis 1551:1558 Pyrosequencing analysis 1536:1558 Pyrosequencing analysis 1536:1558 Pyrosequencing analysis revealed that the NO treatment did not significantly alter the microbial community composition of the membrane biofilm. 25636842 6 59 dep microscopy 902:911 arg1 extraction 958:967 extraction 958:967 extraction 958:967 Confocal microscopy and extracellular polymeric substances (EPS) extraction revealed that PROLI NONOate treatment led to a 48% reduction in polysaccharides, a 66% reduction in proteins, and a 29% reduction in microbial cells compared to the untreated control. 25636842 4 60 theme mixed-species 632:644 arg1 biofilms 646:653 successfully dispersed mixed-species biofilms 609:653 successfully dispersed mixed-species biofilms 609:653 Confocal microscopy revealed that PROLI NONOate exposure induced biofilm dispersal in all but two of the bacteria tested and successfully dispersed mixed-species biofilms. 25636842 5 61 theme 40 672:673 arg1 μM 675:676 μM 675:676 μM 675:676 The addition of 40 μM PROLI NONOate at 24-h intervals to a laboratory-scale RO system led to a 92% reduction in the rate of biofouling (pressure rise over a given period) by a bacterial community cultured from an industrial RO membrane. 25636842 6 62 theme untreated 1134:1142 arg1 control 1144:1150 the untreated control 1130:1150 the untreated control 1130:1150 Confocal microscopy and extracellular polymeric substances (EPS) extraction revealed that PROLI NONOate treatment led to a 48% reduction in polysaccharides, a 66% reduction in proteins, and a 29% reduction in microbial cells compared to the untreated control. 25636842 5 63 theme PROLI 678:682 arg1 NONOate 684:690 40 μM PROLI NONOate 672:690 40 μM PROLI NONOate 672:690 The addition of 40 μM PROLI NONOate at 24-h intervals to a laboratory-scale RO system led to a 92% reduction in the rate of biofouling (pressure rise over a given period) by a bacterial community cultured from an industrial RO membrane. 25636842 2 64 theme PROLI 247:251 arg1 NONOate 253:259 PROLI NONOate 247:259 PROLI NONOate 247:259 This study investigated the dispersal potential of the nitric oxide (NO) donor compound, PROLI NONOate, on single- and mixed-species biofilms formed by bacteria isolated from industrial membrane bioreactor and reverse osmosis (RO) membranes. 25636842 2 64 theme PROLI 247:251 arg1 oxide 220:224 the nitric oxide 209:224 the nitric oxide (NO) donor compound 209:244 This study investigated the dispersal potential of the nitric oxide (NO) donor compound, PROLI NONOate, on single- and mixed-species biofilms formed by bacteria isolated from industrial membrane bioreactor and reverse osmosis (RO) membranes. 25636842 1 65 theme membrane-based 118:131 arg1 systems 149:155 membrane-based water treatment systems 118:155 membrane-based water treatment systems 118:155 Biofouling remains a key challenge for membrane-based water treatment systems. 25636842 6 66 theme NONOate 989:995 arg1 treatment 997:1005 PROLI NONOate treatment 983:1005 PROLI NONOate treatment 983:1005 Confocal microscopy and extracellular polymeric substances (EPS) extraction revealed that PROLI NONOate treatment led to a 48% reduction in polysaccharides, a 66% reduction in proteins, and a 29% reduction in microbial cells compared to the untreated control. 25636842 7 67 theme average 1248:1254 arg1 thickness 1256:1264 average thickness 1248:1264 average thickness (20 μm compared to 26 μm, treated compared to control) 1248:1319 A reduction in biofilm surface coverage (59% compared to 98%, treated compared to control) and average thickness (20 μm compared to 26 μm, treated compared to control) was also observed. 25636842 0 68 theme membrane 58:65 arg1 biofouling 67:76 reverse osmosis membrane biofouling 42:76 reverse osmosis membrane biofouling 42:76 Nitric oxide treatment for the control of reverse osmosis membrane biofouling. 25636842 1 69 theme treatment 139:147 arg1 systems 149:155 membrane-based water treatment systems 118:155 membrane-based water treatment systems 118:155 Biofouling remains a key challenge for membrane-based water treatment systems. 25636842 8 70 theme PROLI 1356:1360 arg1 NONOate 1362:1368 PROLI NONOate 1356:1368 PROLI NONOate 1356:1368 The addition of PROLI NONOate led to a 22% increase in the time required for the RO module to reach its maximum transmembrane pressure (TMP), further indicating that NO treatment delayed fouling. 25636842 5 71 from reduction 755:763 arg1 rate 772:775 the rate 768:775 the rate of biofouling (pressure rise over a given period) by a bacterial community cultured from an industrial RO membrane 768:890 The addition of 40 μM PROLI NONOate at 24-h intervals to a laboratory-scale RO system led to a 92% reduction in the rate of biofouling (pressure rise over a given period) by a bacterial community cultured from an industrial RO membrane. 25636842 7 72 dep coverage 1184:1191 arg1 % 1196:1196 59% 1194:1196 59% compared to 98%, treated compared to control 1194:1241 A reduction in biofilm surface coverage (59% compared to 98%, treated compared to control) and average thickness (20 μm compared to 26 μm, treated compared to control) was also observed. 25636842 6 73 from reduction 1089:1097 arg1 cells 1112:1116 microbial cells 1102:1116 microbial cells 1102:1116 Confocal microscopy and extracellular polymeric substances (EPS) extraction revealed that PROLI NONOate treatment led to a 48% reduction in polysaccharides, a 66% reduction in proteins, and a 29% reduction in microbial cells compared to the untreated control. 25636842 6 73 from reduction 1089:1097 arg1 polysaccharides 1033:1047 polysaccharides 1033:1047 polysaccharides 1033:1047 Confocal microscopy and extracellular polymeric substances (EPS) extraction revealed that PROLI NONOate treatment led to a 48% reduction in polysaccharides, a 66% reduction in proteins, and a 29% reduction in microbial cells compared to the untreated control. 25636842 6 73 from reduction 1089:1097 arg1 proteins 1069:1076 proteins 1069:1076 proteins 1069:1076 Confocal microscopy and extracellular polymeric substances (EPS) extraction revealed that PROLI NONOate treatment led to a 48% reduction in polysaccharides, a 66% reduction in proteins, and a 29% reduction in microbial cells compared to the untreated control. 25636842 5 74 theme RO 732:733 arg1 system 735:740 a laboratory-scale RO system 713:740 a laboratory-scale RO system 713:740 The addition of 40 μM PROLI NONOate at 24-h intervals to a laboratory-scale RO system led to a 92% reduction in the rate of biofouling (pressure rise over a given period) by a bacterial community cultured from an industrial RO membrane. 25636842 5 75 theme industrial 869:878 arg1 membrane 883:890 an industrial RO membrane 866:890 an industrial RO membrane 866:890 The addition of 40 μM PROLI NONOate at 24-h intervals to a laboratory-scale RO system led to a 92% reduction in the rate of biofouling (pressure rise over a given period) by a bacterial community cultured from an industrial RO membrane. 25636842 9 76 theme microbial 1623:1631 arg1 composition 1643:1653 the microbial community composition 1619:1653 the microbial community composition of the membrane biofilm 1619:1677 Pyrosequencing analysis revealed that the NO treatment did not significantly alter the microbial community composition of the membrane biofilm. 25636842 8 77 theme % 1381:1381 arg1 increase 1383:1390 a 22% increase 1377:1390 a 22% increase in the time required for the RO module to reach its maximum transmembrane pressure (TMP) 1377:1479 The addition of PROLI NONOate led to a 22% increase in the time required for the RO module to reach its maximum transmembrane pressure (TMP), further indicating that NO treatment delayed fouling. 25636842 3 78 theme NONOate 423:429 arg1 potential 404:412 The potential 400:412 The potential of PROLI NONOate to control RO membrane biofouling 400:463 The potential of PROLI NONOate to control RO membrane biofouling was also examined. 25636842 6 79 theme % 1018:1018 arg1 reduction 1020:1028 a 48% reduction 1014:1028 a 48% reduction in polysaccharides 1014:1047 Confocal microscopy and extracellular polymeric substances (EPS) extraction revealed that PROLI NONOate treatment led to a 48% reduction in polysaccharides, a 66% reduction in proteins, and a 29% reduction in microbial cells compared to the untreated control. 25636842 4 80 theme biofilm 549:555 arg1 dispersal 557:565 biofilm dispersal 549:565 biofilm dispersal 549:565 Confocal microscopy revealed that PROLI NONOate exposure induced biofilm dispersal in all but two of the bacteria tested and successfully dispersed mixed-species biofilms. 25636842 2 81 theme reverse 368:374 arg1 RO 385:386 RO 385:386 RO 385:386 This study investigated the dispersal potential of the nitric oxide (NO) donor compound, PROLI NONOate, on single- and mixed-species biofilms formed by bacteria isolated from industrial membrane bioreactor and reverse osmosis (RO) membranes. 25636842 2 81 theme reverse 368:374 arg1 osmosis 376:382 reverse osmosis 368:382 reverse osmosis (RO) 368:387 This study investigated the dispersal potential of the nitric oxide (NO) donor compound, PROLI NONOate, on single- and mixed-species biofilms formed by bacteria isolated from industrial membrane bioreactor and reverse osmosis (RO) membranes. 25636842 5 82 theme biofouling 780:789 arg1 rate 772:775 the rate 768:775 the rate of biofouling (pressure rise over a given period) by a bacterial community cultured from an industrial RO membrane 768:890 The addition of 40 μM PROLI NONOate at 24-h intervals to a laboratory-scale RO system led to a 92% reduction in the rate of biofouling (pressure rise over a given period) by a bacterial community cultured from an industrial RO membrane. 25636842 2 83 theme dispersal 186:194 arg1 potential 196:204 the dispersal potential 182:204 the dispersal potential of the nitric oxide (NO) donor compound, PROLI NONOate, on single- and mixed-species biofilms formed by bacteria isolated from industrial membrane bioreactor and reverse osmosis (RO) membranes 182:397 This study investigated the dispersal potential of the nitric oxide (NO) donor compound, PROLI NONOate, on single- and mixed-species biofilms formed by bacteria isolated from industrial membrane bioreactor and reverse osmosis (RO) membranes. 25636842 3 84 theme membrane 445:452 arg1 biofouling 454:463 control RO membrane biofouling 434:463 control RO membrane biofouling 434:463 The potential of PROLI NONOate to control RO membrane biofouling was also examined. 25636842 5 85 theme % 753:753 arg1 reduction 755:763 a 92% reduction 749:763 a 92% reduction in the rate of biofouling (pressure rise over a given period) by a bacterial community cultured from an industrial RO membrane 749:890 The addition of 40 μM PROLI NONOate at 24-h intervals to a laboratory-scale RO system led to a 92% reduction in the rate of biofouling (pressure rise over a given period) by a bacterial community cultured from an industrial RO membrane. 25636842 9 86 theme biofilm 1671:1677 arg1 composition 1643:1653 the microbial community composition 1619:1653 the microbial community composition of the membrane biofilm 1619:1677 Pyrosequencing analysis revealed that the NO treatment did not significantly alter the microbial community composition of the membrane biofilm. 25636842 4 87 theme PROLI 518:522 arg1 exposure 532:539 PROLI NONOate exposure 518:539 PROLI NONOate exposure 518:539 Confocal microscopy revealed that PROLI NONOate exposure induced biofilm dispersal in all but two of the bacteria tested and successfully dispersed mixed-species biofilms. 25636842 6 88 from reduction 1056:1064 arg1 polysaccharides 1033:1047 polysaccharides 1033:1047 polysaccharides 1033:1047 Confocal microscopy and extracellular polymeric substances (EPS) extraction revealed that PROLI NONOate treatment led to a 48% reduction in polysaccharides, a 66% reduction in proteins, and a 29% reduction in microbial cells compared to the untreated control. 25636842 6 88 from reduction 1056:1064 arg1 cells 1112:1116 microbial cells 1102:1116 microbial cells 1102:1116 Confocal microscopy and extracellular polymeric substances (EPS) extraction revealed that PROLI NONOate treatment led to a 48% reduction in polysaccharides, a 66% reduction in proteins, and a 29% reduction in microbial cells compared to the untreated control. 25636842 6 88 from reduction 1056:1064 arg1 proteins 1069:1076 proteins 1069:1076 proteins 1069:1076 Confocal microscopy and extracellular polymeric substances (EPS) extraction revealed that PROLI NONOate treatment led to a 48% reduction in polysaccharides, a 66% reduction in proteins, and a 29% reduction in microbial cells compared to the untreated control. 25636842 3 89 theme control 434:440 arg1 biofouling 454:463 control RO membrane biofouling 434:463 control RO membrane biofouling 434:463 The potential of PROLI NONOate to control RO membrane biofouling was also examined. 25636842 0 90 theme reverse 42:48 arg1 biofouling 67:76 reverse osmosis membrane biofouling 42:76 reverse osmosis membrane biofouling 42:76 Nitric oxide treatment for the control of reverse osmosis membrane biofouling. 25636842 8 91 theme RO 1421:1422 arg1 module 1424:1429 the RO module 1417:1429 the RO module 1417:1429 The addition of PROLI NONOate led to a 22% increase in the time required for the RO module to reach its maximum transmembrane pressure (TMP), further indicating that NO treatment delayed fouling. 25636842 2 92 theme nitric 213:218 arg1 NO 227:228 NO 227:228 NO 227:228 This study investigated the dispersal potential of the nitric oxide (NO) donor compound, PROLI NONOate, on single- and mixed-species biofilms formed by bacteria isolated from industrial membrane bioreactor and reverse osmosis (RO) membranes. 25636842 2 92 theme nitric 213:218 arg1 oxide 220:224 the nitric oxide 209:224 the nitric oxide (NO) donor compound 209:244 This study investigated the dispersal potential of the nitric oxide (NO) donor compound, PROLI NONOate, on single- and mixed-species biofilms formed by bacteria isolated from industrial membrane bioreactor and reverse osmosis (RO) membranes. 25636842 2 92 theme nitric 213:218 arg1 NONOate 253:259 PROLI NONOate 247:259 PROLI NONOate 247:259 This study investigated the dispersal potential of the nitric oxide (NO) donor compound, PROLI NONOate, on single- and mixed-species biofilms formed by bacteria isolated from industrial membrane bioreactor and reverse osmosis (RO) membranes. 25636842 7 93 dep compared 1198:1205 arg1 treated 1215:1221 treated 1215:1221 treated compared to control 1215:1241 A reduction in biofilm surface coverage (59% compared to 98%, treated compared to control) and average thickness (20 μm compared to 26 μm, treated compared to control) was also observed. 25636842 7 94 theme biofilm 1168:1174 arg1 coverage 1184:1191 biofilm surface coverage 1168:1191 biofilm surface coverage (59% compared to 98%, treated compared to control) 1168:1242 A reduction in biofilm surface coverage (59% compared to 98%, treated compared to control) and average thickness (20 μm compared to 26 μm, treated compared to control) was also observed. 25636842 2 95 theme bioreactor 353:362 arg1 membranes 389:397 industrial membrane bioreactor and reverse osmosis (RO) membranes 333:397 industrial membrane bioreactor and reverse osmosis (RO) membranes 333:397 This study investigated the dispersal potential of the nitric oxide (NO) donor compound, PROLI NONOate, on single- and mixed-species biofilms formed by bacteria isolated from industrial membrane bioreactor and reverse osmosis (RO) membranes. 24410900 13 0 theme same 1455:1458 arg1 effects 1471:1477 the same modulatory effects 1451:1477 the same modulatory effects on UPR signaling 1451:1494 CONCLUSIONS SARS-CoV and HCoV-HKU1 S proteins use distinct UPR-activating domains to exert the same modulatory effects on UPR signaling. 24410900 10 1 theme UPR 1160:1162 arg1 activation 1142:1151 the activation 1138:1151 the activation of the UPR by S proteins 1138:1176 N-linked glycosylation was not required for the activation of the UPR by S proteins. 24410900 0 2 theme spike 71:75 arg1 proteins 77:84 spike proteins 71:84 spike proteins of severe acute respiratory syndrome coronavirus and human coronavirus HKU1 71:160 Comparative analysis of the activation of unfolded protein response by spike proteins of severe acute respiratory syndrome coronavirus and human coronavirus HKU1. 24410900 8 3 theme activity 978:985 arg1 pattern 952:958 a similar pattern 942:958 a similar pattern of UPR-activating activity 942:985 Both S proteins showed a similar pattern of UPR-activating activity. 24410900 13 4 theme UPR-activating 1419:1432 arg1 domains 1434:1440 distinct UPR-activating domains 1410:1440 distinct UPR-activating domains 1410:1440 CONCLUSIONS SARS-CoV and HCoV-HKU1 S proteins use distinct UPR-activating domains to exert the same modulatory effects on UPR signaling. 24410900 0 5 theme severe 89:94 arg1 coronavirus 123:133 severe acute respiratory syndrome coronavirus 89:133 severe acute respiratory syndrome coronavirus 89:133 Comparative analysis of the activation of unfolded protein response by spike proteins of severe acute respiratory syndrome coronavirus and human coronavirus HKU1. 24410900 11 6 theme counterpart 1214:1224 arg1 subunit 1182:1188 S1 subunit 1179:1188 S1 subunit of SARS-CoV but not its counterpart in HCoV-HKU1 1179:1237 S1 subunit of SARS-CoV but not its counterpart in HCoV-HKU1 was capable of activating the UPR. 24410900 8 7 theme S 924:924 arg1 proteins 926:933 Both S proteins 919:933 Both S proteins 919:933 Both S proteins showed a similar pattern of UPR-activating activity. 24410900 10 8 gly glycosylation 1103:1115 arg1 UPR 1160:1162 the UPR 1156:1162 the UPR 1156:1162 N-linked glycosylation was not required for the activation of the UPR by S proteins. 24410900 4 9 theme UPR-activating 560:573 arg1 domain 575:580 the UPR-activating domain 556:580 the UPR-activating domain in SARS-CoV S protein 556:602 In addition, the UPR-activating domain in SARS-CoV S protein remains to be identified. 24410900 5 10 theme HCoV-HKU1 691:699 arg1 proteins 666:673 S proteins 664:673 S proteins of SARS-CoV and HCoV-HKU1 664:699 RESULTS In this study we compared S proteins of SARS-CoV and HCoV-HKU1 for their ability to activate the UPR. 24410900 1 11 theme human 343:347 arg1 populations 349:359 the human populations 339:359 the human populations causing generally milder illness 339:392 BACKGROUND Whereas severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) is associated with severe disease, human coronavirus HKU1 (HCoV-HKU1) commonly circulates in the human populations causing generally milder illness. 24410900 7 12 theme protease 818:825 arg1 TMPRSS2 827:833 Transmembrane serine protease TMPRSS2 797:833 Transmembrane serine protease TMPRSS2 797:833 Transmembrane serine protease TMPRSS2 catalyzed the cleavage of SARS-CoV S protein, but not the counterpart in HCoV-HKU1. 24410900 1 13 theme severe 265:270 arg1 disease 272:278 severe disease 265:278 severe disease 265:278 BACKGROUND Whereas severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) is associated with severe disease, human coronavirus HKU1 (HCoV-HKU1) commonly circulates in the human populations causing generally milder illness. 24410900 0 14 theme respiratory 102:112 arg1 coronavirus 123:133 severe acute respiratory syndrome coronavirus 89:133 severe acute respiratory syndrome coronavirus 89:133 Comparative analysis of the activation of unfolded protein response by spike proteins of severe acute respiratory syndrome coronavirus and human coronavirus HKU1. 24410900 3 15 theme HCoV-HKU1 501:509 arg1 protein 513:519 HCoV-HKU1 S protein 501:519 HCoV-HKU1 S protein 501:519 It is not understood whether HCoV-HKU1 S protein has similar activity. 24410900 10 16 theme S 1167:1167 arg1 proteins 1169:1176 S proteins 1167:1176 S proteins 1167:1176 N-linked glycosylation was not required for the activation of the UPR by S proteins. 24410900 2 17 theme Spike 395:399 arg1 protein 405:411 Spike (S) protein 395:411 Spike (S) protein of SARS-CoV 395:423 Spike (S) protein of SARS-CoV activates the unfolded protein response (UPR). 24410900 0 18 theme acute 96:100 arg1 coronavirus 123:133 severe acute respiratory syndrome coronavirus 89:133 severe acute respiratory syndrome coronavirus 89:133 Comparative analysis of the activation of unfolded protein response by spike proteins of severe acute respiratory syndrome coronavirus and human coronavirus HKU1. 24410900 13 19 from effects 1471:1477 arg1 signaling 1486:1494 UPR signaling 1482:1494 UPR signaling 1482:1494 CONCLUSIONS SARS-CoV and HCoV-HKU1 S proteins use distinct UPR-activating domains to exert the same modulatory effects on UPR signaling. 24410900 6 20 theme S 745:745 arg1 proteins 747:754 Both S proteins 740:754 Both S proteins 740:754 Both S proteins were found in the endoplasmic reticulum. 24410900 3 21 theme S 511:511 arg1 protein 513:519 HCoV-HKU1 S protein 501:519 HCoV-HKU1 S protein 501:519 It is not understood whether HCoV-HKU1 S protein has similar activity. 24410900 7 22 theme Transmembrane 797:809 arg1 TMPRSS2 827:833 Transmembrane serine protease TMPRSS2 797:833 Transmembrane serine protease TMPRSS2 797:833 Transmembrane serine protease TMPRSS2 catalyzed the cleavage of SARS-CoV S protein, but not the counterpart in HCoV-HKU1. 24410900 1 23 theme severe 182:187 arg1 SARS-CoV 236:243 SARS-CoV 236:243 SARS-CoV 236:243 BACKGROUND Whereas severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) is associated with severe disease, human coronavirus HKU1 (HCoV-HKU1) commonly circulates in the human populations causing generally milder illness. 24410900 1 23 theme severe 182:187 arg1 coronavirus 223:233 severe acute respiratory syndrome (SARS) coronavirus 182:233 severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) 182:244 BACKGROUND Whereas severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) is associated with severe disease, human coronavirus HKU1 (HCoV-HKU1) commonly circulates in the human populations causing generally milder illness. 24410900 5 24 dep RESULTS 630:636 arg1 study 646:650 this study 641:650 this study 641:650 RESULTS In this study we compared S proteins of SARS-CoV and HCoV-HKU1 for their ability to activate the UPR. 24410900 4 25 from domain 575:580 arg1 protein 596:602 SARS-CoV S protein 585:602 SARS-CoV S protein 585:602 In addition, the UPR-activating domain in SARS-CoV S protein remains to be identified. 24410900 8 26 theme similar 944:950 arg1 pattern 952:958 a similar pattern 942:958 a similar pattern of UPR-activating activity 942:985 Both S proteins showed a similar pattern of UPR-activating activity. 24410900 10 27 link N-linked 1094:1101 arg1 glycosylation 1103:1115 N-linked glycosylation 1094:1115 N-linked glycosylation 1094:1115 N-linked glycosylation was not required for the activation of the UPR by S proteins. 24410900 7 28 theme serine 811:816 arg1 TMPRSS2 827:833 Transmembrane serine protease TMPRSS2 797:833 Transmembrane serine protease TMPRSS2 797:833 Transmembrane serine protease TMPRSS2 catalyzed the cleavage of SARS-CoV S protein, but not the counterpart in HCoV-HKU1. 24410900 1 29 theme acute 189:193 arg1 SARS-CoV 236:243 SARS-CoV 236:243 SARS-CoV 236:243 BACKGROUND Whereas severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) is associated with severe disease, human coronavirus HKU1 (HCoV-HKU1) commonly circulates in the human populations causing generally milder illness. 24410900 1 29 theme acute 189:193 arg1 coronavirus 223:233 severe acute respiratory syndrome (SARS) coronavirus 182:233 severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) 182:244 BACKGROUND Whereas severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) is associated with severe disease, human coronavirus HKU1 (HCoV-HKU1) commonly circulates in the human populations causing generally milder illness. 24410900 0 30 theme Comparative 0:10 arg1 analysis 12:19 Comparative analysis 0:19 Comparative analysis of the activation of unfolded protein response by spike proteins of severe acute respiratory syndrome coronavirus and human coronavirus HKU1. 0:161 Comparative analysis of the activation of unfolded protein response by spike proteins of severe acute respiratory syndrome coronavirus and human coronavirus HKU1. 24410900 10 31 theme N-linked 1094:1101 arg1 glycosylation 1103:1115 N-linked glycosylation 1094:1115 N-linked glycosylation 1094:1115 N-linked glycosylation was not required for the activation of the UPR by S proteins. 24410900 8 32 theme UPR-activating 963:976 arg1 activity 978:985 UPR-activating activity 963:985 UPR-activating activity 963:985 Both S proteins showed a similar pattern of UPR-activating activity. 24410900 9 33 theme genes 1057:1061 arg1 transcription 1027:1039 the transcription 1023:1039 the transcription of UPR effector genes such as Grp78, Grp94 and CHOP 1023:1091 Through PERK kinase they activated the transcription of UPR effector genes such as Grp78, Grp94 and CHOP. 24410900 1 34 theme respiratory 195:205 arg1 SARS-CoV 236:243 SARS-CoV 236:243 SARS-CoV 236:243 BACKGROUND Whereas severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) is associated with severe disease, human coronavirus HKU1 (HCoV-HKU1) commonly circulates in the human populations causing generally milder illness. 24410900 1 34 theme respiratory 195:205 arg1 coronavirus 223:233 severe acute respiratory syndrome (SARS) coronavirus 182:233 severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) 182:244 BACKGROUND Whereas severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) is associated with severe disease, human coronavirus HKU1 (HCoV-HKU1) commonly circulates in the human populations causing generally milder illness. 24410900 2 35 theme SARS-CoV 416:423 arg1 protein 405:411 Spike (S) protein 395:411 Spike (S) protein of SARS-CoV 395:423 Spike (S) protein of SARS-CoV activates the unfolded protein response (UPR). 24410900 11 36 from HCoV-HKU1 1229:1237 arg1 subunit 1182:1188 S1 subunit 1179:1188 S1 subunit of SARS-CoV but not its counterpart in HCoV-HKU1 1179:1237 S1 subunit of SARS-CoV but not its counterpart in HCoV-HKU1 was capable of activating the UPR. 24410900 0 37 theme coronavirus 123:133 arg1 proteins 77:84 spike proteins 71:84 spike proteins of severe acute respiratory syndrome coronavirus and human coronavirus HKU1 71:160 Comparative analysis of the activation of unfolded protein response by spike proteins of severe acute respiratory syndrome coronavirus and human coronavirus HKU1. 24410900 13 38 theme UPR 1482:1484 arg1 signaling 1486:1494 UPR signaling 1482:1494 UPR signaling 1482:1494 CONCLUSIONS SARS-CoV and HCoV-HKU1 S proteins use distinct UPR-activating domains to exert the same modulatory effects on UPR signaling. 24410900 3 39 theme similar 525:531 arg1 activity 533:540 similar activity 525:540 similar activity 525:540 It is not understood whether HCoV-HKU1 S protein has similar activity. 24410900 13 40 theme modulatory 1460:1469 arg1 effects 1471:1477 the same modulatory effects 1451:1477 the same modulatory effects on UPR signaling 1451:1494 CONCLUSIONS SARS-CoV and HCoV-HKU1 S proteins use distinct UPR-activating domains to exert the same modulatory effects on UPR signaling. 24410900 1 41 theme syndrome 207:214 arg1 SARS-CoV 236:243 SARS-CoV 236:243 SARS-CoV 236:243 BACKGROUND Whereas severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) is associated with severe disease, human coronavirus HKU1 (HCoV-HKU1) commonly circulates in the human populations causing generally milder illness. 24410900 1 41 theme syndrome 207:214 arg1 coronavirus 223:233 severe acute respiratory syndrome (SARS) coronavirus 182:233 severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) 182:244 BACKGROUND Whereas severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) is associated with severe disease, human coronavirus HKU1 (HCoV-HKU1) commonly circulates in the human populations causing generally milder illness. 24410900 1 42 theme human 281:285 arg1 HCoV-HKU1 305:313 HCoV-HKU1 305:313 HCoV-HKU1 305:313 BACKGROUND Whereas severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) is associated with severe disease, human coronavirus HKU1 (HCoV-HKU1) commonly circulates in the human populations causing generally milder illness. 24410900 1 42 theme human 281:285 arg1 HKU1 299:302 human coronavirus HKU1 281:302 human coronavirus HKU1 (HCoV-HKU1) 281:314 BACKGROUND Whereas severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) is associated with severe disease, human coronavirus HKU1 (HCoV-HKU1) commonly circulates in the human populations causing generally milder illness. 24410900 0 43 theme syndrome 114:121 arg1 coronavirus 123:133 severe acute respiratory syndrome coronavirus 89:133 severe acute respiratory syndrome coronavirus 89:133 Comparative analysis of the activation of unfolded protein response by spike proteins of severe acute respiratory syndrome coronavirus and human coronavirus HKU1. 24410900 1 44 theme milder 379:384 arg1 illness 386:392 generally milder illness 369:392 generally milder illness 369:392 BACKGROUND Whereas severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) is associated with severe disease, human coronavirus HKU1 (HCoV-HKU1) commonly circulates in the human populations causing generally milder illness. 24410900 11 45 from subunit 1182:1188 arg1 HCoV-HKU1 1229:1237 HCoV-HKU1 1229:1237 HCoV-HKU1 1229:1237 S1 subunit of SARS-CoV but not its counterpart in HCoV-HKU1 was capable of activating the UPR. 24410900 2 46 theme protein 448:454 arg1 UPR 466:468 UPR 466:468 UPR 466:468 Spike (S) protein of SARS-CoV activates the unfolded protein response (UPR). 24410900 2 46 theme protein 448:454 arg1 response 456:463 the unfolded protein response 435:463 the unfolded protein response (UPR) 435:469 Spike (S) protein of SARS-CoV activates the unfolded protein response (UPR). 24410900 13 47 theme HCoV-HKU1 1385:1393 arg1 proteins 1397:1404 HCoV-HKU1 S proteins 1385:1404 HCoV-HKU1 S proteins 1385:1404 CONCLUSIONS SARS-CoV and HCoV-HKU1 S proteins use distinct UPR-activating domains to exert the same modulatory effects on UPR signaling. 24410900 1 48 theme coronavirus 287:297 arg1 HCoV-HKU1 305:313 HCoV-HKU1 305:313 HCoV-HKU1 305:313 BACKGROUND Whereas severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) is associated with severe disease, human coronavirus HKU1 (HCoV-HKU1) commonly circulates in the human populations causing generally milder illness. 24410900 1 48 theme coronavirus 287:297 arg1 HKU1 299:302 human coronavirus HKU1 281:302 human coronavirus HKU1 (HCoV-HKU1) 281:314 BACKGROUND Whereas severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) is associated with severe disease, human coronavirus HKU1 (HCoV-HKU1) commonly circulates in the human populations causing generally milder illness. 24410900 0 49 theme human 139:143 arg1 HKU1 157:160 human coronavirus HKU1 139:160 human coronavirus HKU1 139:160 Comparative analysis of the activation of unfolded protein response by spike proteins of severe acute respiratory syndrome coronavirus and human coronavirus HKU1. 24410900 2 50 theme S 402:402 arg1 protein 405:411 Spike (S) protein 395:411 Spike (S) protein of SARS-CoV 395:423 Spike (S) protein of SARS-CoV activates the unfolded protein response (UPR). 24410900 11 51 theme SARS-CoV 1193:1200 arg1 subunit 1182:1188 S1 subunit 1179:1188 S1 subunit of SARS-CoV but not its counterpart in HCoV-HKU1 1179:1237 S1 subunit of SARS-CoV but not its counterpart in HCoV-HKU1 was capable of activating the UPR. 24410900 9 52 theme PERK 996:999 arg1 kinase 1001:1006 PERK kinase 996:1006 PERK kinase 996:1006 Through PERK kinase they activated the transcription of UPR effector genes such as Grp78, Grp94 and CHOP. 24410900 1 53 theme SARS 217:220 arg1 SARS-CoV 236:243 SARS-CoV 236:243 SARS-CoV 236:243 BACKGROUND Whereas severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) is associated with severe disease, human coronavirus HKU1 (HCoV-HKU1) commonly circulates in the human populations causing generally milder illness. 24410900 1 53 theme SARS 217:220 arg1 coronavirus 223:233 severe acute respiratory syndrome (SARS) coronavirus 182:233 severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) 182:244 BACKGROUND Whereas severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) is associated with severe disease, human coronavirus HKU1 (HCoV-HKU1) commonly circulates in the human populations causing generally milder illness. 24410900 0 54 theme activation 28:37 arg1 analysis 12:19 Comparative analysis 0:19 Comparative analysis of the activation of unfolded protein response by spike proteins of severe acute respiratory syndrome coronavirus and human coronavirus HKU1. 0:161 Comparative analysis of the activation of unfolded protein response by spike proteins of severe acute respiratory syndrome coronavirus and human coronavirus HKU1. 24410900 13 55 theme distinct 1410:1417 arg1 domains 1434:1440 distinct UPR-activating domains 1410:1440 distinct UPR-activating domains 1410:1440 CONCLUSIONS SARS-CoV and HCoV-HKU1 S proteins use distinct UPR-activating domains to exert the same modulatory effects on UPR signaling. 24410900 5 56 theme SARS-CoV 678:685 arg1 proteins 666:673 S proteins 664:673 S proteins of SARS-CoV and HCoV-HKU1 664:699 RESULTS In this study we compared S proteins of SARS-CoV and HCoV-HKU1 for their ability to activate the UPR. 24410900 9 57 theme effector 1048:1055 arg1 CHOP 1088:1091 CHOP 1088:1091 CHOP 1088:1091 Through PERK kinase they activated the transcription of UPR effector genes such as Grp78, Grp94 and CHOP. 24410900 9 57 theme effector 1048:1055 arg1 Grp94 1078:1082 Grp94 1078:1082 Grp94 1078:1082 Through PERK kinase they activated the transcription of UPR effector genes such as Grp78, Grp94 and CHOP. 24410900 9 57 theme effector 1048:1055 arg1 genes 1057:1061 UPR effector genes 1044:1061 UPR effector genes such as Grp78, Grp94 and CHOP 1044:1091 Through PERK kinase they activated the transcription of UPR effector genes such as Grp78, Grp94 and CHOP. 24410900 9 57 theme effector 1048:1055 arg1 Grp78 1071:1075 Grp78 1071:1075 Grp78 1071:1075 Through PERK kinase they activated the transcription of UPR effector genes such as Grp78, Grp94 and CHOP. 24410900 0 58 theme protein 51:57 arg1 response 59:66 unfolded protein response 42:66 unfolded protein response 42:66 Comparative analysis of the activation of unfolded protein response by spike proteins of severe acute respiratory syndrome coronavirus and human coronavirus HKU1. 24410900 6 59 located found 761:765 arg1 reticulum 786:794 the endoplasmic reticulum 770:794 the endoplasmic reticulum 770:794 Both S proteins were found in the endoplasmic reticulum. 24410900 6 59 located found 761:765 arg2 proteins 747:754 Both S proteins 740:754 Both S proteins 740:754 Both S proteins were found in the endoplasmic reticulum. 24410900 0 60 theme HKU1 157:160 arg1 proteins 77:84 spike proteins 71:84 spike proteins of severe acute respiratory syndrome coronavirus and human coronavirus HKU1 71:160 Comparative analysis of the activation of unfolded protein response by spike proteins of severe acute respiratory syndrome coronavirus and human coronavirus HKU1. 24410900 0 61 theme unfolded 42:49 arg1 response 59:66 unfolded protein response 42:66 unfolded protein response 42:66 Comparative analysis of the activation of unfolded protein response by spike proteins of severe acute respiratory syndrome coronavirus and human coronavirus HKU1. 24410900 3 62 contain has 521:523 arg1 protein 513:519 HCoV-HKU1 S protein 501:519 HCoV-HKU1 S protein 501:519 It is not understood whether HCoV-HKU1 S protein has similar activity. 24410900 3 62 contain has 521:523 arg2 activity 533:540 similar activity 525:540 similar activity 525:540 It is not understood whether HCoV-HKU1 S protein has similar activity. 24410900 0 63 theme coronavirus 145:155 arg1 HKU1 157:160 human coronavirus HKU1 139:160 human coronavirus HKU1 139:160 Comparative analysis of the activation of unfolded protein response by spike proteins of severe acute respiratory syndrome coronavirus and human coronavirus HKU1. 24410900 2 64 theme unfolded 439:446 arg1 UPR 466:468 UPR 466:468 UPR 466:468 Spike (S) protein of SARS-CoV activates the unfolded protein response (UPR). 24410900 2 64 theme unfolded 439:446 arg1 response 456:463 the unfolded protein response 435:463 the unfolded protein response (UPR) 435:469 Spike (S) protein of SARS-CoV activates the unfolded protein response (UPR). 24410900 12 65 theme central 1276:1282 arg1 acids 1298:1302 amino acids 201-400 1292:1310 amino acids 201-400 1292:1310 A central region (amino acids 201-400) of SARS-CoV S1 was required for this activity. 24410900 12 65 theme central 1276:1282 arg1 region 1284:1289 A central region 1274:1289 A central region (amino acids 201-400) of SARS-CoV S1 1274:1326 A central region (amino acids 201-400) of SARS-CoV S1 was required for this activity. 24410900 7 66 theme protein 872:878 arg1 cleavage 849:856 the cleavage 845:856 the cleavage of SARS-CoV S protein 845:878 Transmembrane serine protease TMPRSS2 catalyzed the cleavage of SARS-CoV S protein, but not the counterpart in HCoV-HKU1. 24410900 11 67 from counterpart 1214:1224 arg1 HCoV-HKU1 1229:1237 HCoV-HKU1 1229:1237 HCoV-HKU1 1229:1237 S1 subunit of SARS-CoV but not its counterpart in HCoV-HKU1 was capable of activating the UPR. 24410900 11 68 theme S1 1179:1180 arg1 subunit 1182:1188 S1 subunit 1179:1188 S1 subunit of SARS-CoV but not its counterpart in HCoV-HKU1 1179:1237 S1 subunit of SARS-CoV but not its counterpart in HCoV-HKU1 was capable of activating the UPR. 24410900 12 69 theme amino 1292:1296 arg1 acids 1298:1302 amino acids 201-400 1292:1310 amino acids 201-400 1292:1310 A central region (amino acids 201-400) of SARS-CoV S1 was required for this activity. 24410900 12 69 theme amino 1292:1296 arg1 region 1284:1289 A central region 1274:1289 A central region (amino acids 201-400) of SARS-CoV S1 1274:1326 A central region (amino acids 201-400) of SARS-CoV S1 was required for this activity. 24410900 12 70 theme S1 1325:1326 arg1 acids 1298:1302 amino acids 201-400 1292:1310 amino acids 201-400 1292:1310 A central region (amino acids 201-400) of SARS-CoV S1 was required for this activity. 24410900 12 70 theme S1 1325:1326 arg1 region 1284:1289 A central region 1274:1289 A central region (amino acids 201-400) of SARS-CoV S1 1274:1326 A central region (amino acids 201-400) of SARS-CoV S1 was required for this activity. 24410900 12 71 theme SARS-CoV 1316:1323 arg1 S1 1325:1326 SARS-CoV S1 1316:1326 SARS-CoV S1 1316:1326 A central region (amino acids 201-400) of SARS-CoV S1 was required for this activity. 24410900 6 72 theme endoplasmic 774:784 arg1 reticulum 786:794 the endoplasmic reticulum 770:794 the endoplasmic reticulum 770:794 Both S proteins were found in the endoplasmic reticulum. 24410900 13 73 dep CONCLUSIONS 1360:1370 arg1 proteins 1397:1404 HCoV-HKU1 S proteins 1385:1404 HCoV-HKU1 S proteins 1385:1404 CONCLUSIONS SARS-CoV and HCoV-HKU1 S proteins use distinct UPR-activating domains to exert the same modulatory effects on UPR signaling. 24410900 13 73 dep CONCLUSIONS 1360:1370 arg1 SARS-CoV 1372:1379 SARS-CoV 1372:1379 SARS-CoV 1372:1379 CONCLUSIONS SARS-CoV and HCoV-HKU1 S proteins use distinct UPR-activating domains to exert the same modulatory effects on UPR signaling. 24410900 7 74 from counterpart 893:903 arg1 HCoV-HKU1 908:916 HCoV-HKU1 908:916 HCoV-HKU1 908:916 Transmembrane serine protease TMPRSS2 catalyzed the cleavage of SARS-CoV S protein, but not the counterpart in HCoV-HKU1. 24410900 7 75 theme SARS-CoV 861:868 arg1 protein 872:878 SARS-CoV S protein 861:878 SARS-CoV S protein 861:878 Transmembrane serine protease TMPRSS2 catalyzed the cleavage of SARS-CoV S protein, but not the counterpart in HCoV-HKU1. 24410900 9 76 theme UPR 1044:1046 arg1 CHOP 1088:1091 CHOP 1088:1091 CHOP 1088:1091 Through PERK kinase they activated the transcription of UPR effector genes such as Grp78, Grp94 and CHOP. 24410900 9 76 theme UPR 1044:1046 arg1 Grp94 1078:1082 Grp94 1078:1082 Grp94 1078:1082 Through PERK kinase they activated the transcription of UPR effector genes such as Grp78, Grp94 and CHOP. 24410900 9 76 theme UPR 1044:1046 arg1 genes 1057:1061 UPR effector genes 1044:1061 UPR effector genes such as Grp78, Grp94 and CHOP 1044:1091 Through PERK kinase they activated the transcription of UPR effector genes such as Grp78, Grp94 and CHOP. 24410900 9 76 theme UPR 1044:1046 arg1 Grp78 1071:1075 Grp78 1071:1075 Grp78 1071:1075 Through PERK kinase they activated the transcription of UPR effector genes such as Grp78, Grp94 and CHOP. 24410900 13 77 theme S 1395:1395 arg1 proteins 1397:1404 HCoV-HKU1 S proteins 1385:1404 HCoV-HKU1 S proteins 1385:1404 CONCLUSIONS SARS-CoV and HCoV-HKU1 S proteins use distinct UPR-activating domains to exert the same modulatory effects on UPR signaling. 24410900 7 78 theme S 870:870 arg1 protein 872:878 SARS-CoV S protein 861:878 SARS-CoV S protein 861:878 Transmembrane serine protease TMPRSS2 catalyzed the cleavage of SARS-CoV S protein, but not the counterpart in HCoV-HKU1. 24410900 4 79 theme S 594:594 arg1 protein 596:602 SARS-CoV S protein 585:602 SARS-CoV S protein 585:602 In addition, the UPR-activating domain in SARS-CoV S protein remains to be identified. 24410900 0 80 theme response 59:66 arg1 activation 28:37 the activation 24:37 the activation of unfolded protein response 24:66 Comparative analysis of the activation of unfolded protein response by spike proteins of severe acute respiratory syndrome coronavirus and human coronavirus HKU1. 24410900 5 81 theme S 664:664 arg1 proteins 666:673 S proteins 664:673 S proteins of SARS-CoV and HCoV-HKU1 664:699 RESULTS In this study we compared S proteins of SARS-CoV and HCoV-HKU1 for their ability to activate the UPR. 24410900 4 82 theme SARS-CoV 585:592 arg1 protein 596:602 SARS-CoV S protein 585:602 SARS-CoV S protein 585:602 In addition, the UPR-activating domain in SARS-CoV S protein remains to be identified. 24328033 8 0 theme new 1089:1091 arg1 particles 1093:1101 The new particles 1085:1101 The new particles 1085:1101 The new particles enabled the highly sensitive and selective enrichment of glycopeptides from a digestion mixture of fetuin, even from a background mixture of non-glycosylated protein that was 100-fold more abundant. 24328033 10 1 gly glycopeptides 1565:1577 arg2 glycopeptides 1565:1577 N-linked glycopeptides 1556:1577 N-linked glycopeptides from mouse liver tissues, which resulted in the assignment of 511 unique glycopeptides belonging to 372 different glycoproteins 1556:1705 Finally, the novel multivalent hydrazide-functionalized particles were applied in the enrichment of N-linked glycopeptides from mouse liver tissues, which resulted in the assignment of 511 unique glycopeptides belonging to 372 different glycoproteins. 24328033 10 1 gly glycopeptides 1565:1577 arg1 tissues 1596:1602 mouse liver tissues 1584:1602 mouse liver tissues 1584:1602 Finally, the novel multivalent hydrazide-functionalized particles were applied in the enrichment of N-linked glycopeptides from mouse liver tissues, which resulted in the assignment of 511 unique glycopeptides belonging to 372 different glycoproteins. 24328033 10 2 theme unique 1645:1650 arg1 glycopeptides 1652:1664 511 unique glycopeptides 1641:1664 511 unique glycopeptides belonging to 372 different glycoproteins 1641:1705 Finally, the novel multivalent hydrazide-functionalized particles were applied in the enrichment of N-linked glycopeptides from mouse liver tissues, which resulted in the assignment of 511 unique glycopeptides belonging to 372 different glycoproteins. 24328033 11 3 theme multivalent 1762:1772 arg1 particles 1774:1782 the multivalent particles 1758:1782 the multivalent particles 1758:1782 The results further demonstrated the potential of the multivalent particles for glycopeptide enrichment in complex proteomics samples. 24328033 5 4 theme nanoparticle 709:720 arg1 coating 722:728 a new functionalized magnetic nanoparticle coating 679:728 a new functionalized magnetic nanoparticle coating with hydrazide-modified non-crosslinked polymer chains 679:783 Here, we introduce a new functionalized magnetic nanoparticle coating with hydrazide-modified non-crosslinked polymer chains. 24328033 4 5 theme glycosylation 645:657 arg1 microheterogeneities 621:640 the microheterogeneities 617:640 the microheterogeneities of glycosylation 617:657 Therefore, these materials can only provide a limited reaction rate with glycopeptides in complex protein samples, which is exacerbated by the microheterogeneities of glycosylation. 24328033 11 6 theme complex 1815:1821 arg1 samples 1834:1840 complex proteomics samples 1815:1840 complex proteomics samples 1815:1840 The results further demonstrated the potential of the multivalent particles for glycopeptide enrichment in complex proteomics samples. 24328033 9 7 theme glycopeptides 1324:1336 arg1 ratio 1315:1319 The recovery ratio 1302:1319 The recovery ratio of glycopeptides 1302:1336 The recovery ratio of glycopeptides was determined to be 77.8%, and the glycopeptide binding capacity of the materials was determined to be 25 μg mg(-1). 24328033 9 7 theme glycopeptides 1324:1336 arg1 % 1363:1363 77.8% 1359:1363 77.8% 1359:1363 The recovery ratio of glycopeptides was determined to be 77.8%, and the glycopeptide binding capacity of the materials was determined to be 25 μg mg(-1). 24328033 6 8 theme SI-ATRP 917:923 arg1 technique 926:934 the surface-initiated atom transfer radical polymerization (SI-ATRP) technique 857:934 the surface-initiated atom transfer radical polymerization (SI-ATRP) technique 857:934 The multivalent hydrazide-functionalized particles were synthesized by the surface-initiated atom transfer radical polymerization (SI-ATRP) technique. 24328033 4 9 gly glycopeptides 551:563 arg2 glycopeptides 551:563 glycopeptides 551:563 glycopeptides 551:563 Therefore, these materials can only provide a limited reaction rate with glycopeptides in complex protein samples, which is exacerbated by the microheterogeneities of glycosylation. 24328033 5 10 theme functionalized 685:698 arg1 coating 722:728 a new functionalized magnetic nanoparticle coating 679:728 a new functionalized magnetic nanoparticle coating with hydrazide-modified non-crosslinked polymer chains 679:783 Here, we introduce a new functionalized magnetic nanoparticle coating with hydrazide-modified non-crosslinked polymer chains. 24328033 6 11 theme polymerization 901:914 arg1 technique 926:934 the surface-initiated atom transfer radical polymerization (SI-ATRP) technique 857:934 the surface-initiated atom transfer radical polymerization (SI-ATRP) technique 857:934 The multivalent hydrazide-functionalized particles were synthesized by the surface-initiated atom transfer radical polymerization (SI-ATRP) technique. 24328033 10 12 from enrichment 1542:1551 arg1 tissues 1596:1602 mouse liver tissues 1584:1602 mouse liver tissues 1584:1602 Finally, the novel multivalent hydrazide-functionalized particles were applied in the enrichment of N-linked glycopeptides from mouse liver tissues, which resulted in the assignment of 511 unique glycopeptides belonging to 372 different glycoproteins. 24328033 11 13 gly glycopeptide 1788:1799 arg2 glycopeptide 1788:1799 glycopeptide enrichment 1788:1810 glycopeptide enrichment in complex proteomics samples 1788:1840 The results further demonstrated the potential of the multivalent particles for glycopeptide enrichment in complex proteomics samples. 24328033 1 14 gly glycopeptide 147:158 arg2 glycopeptide 147:158 global glycopeptide enrichment 140:169 global glycopeptide enrichment 140:169 Among the common approaches for global glycopeptide enrichment, hydrazide chemistry is well recognized. 24328033 2 15 theme single 286:291 arg1 layer 293:297 a single layer 284:297 a single layer of hydrazide functional groups 284:328 However, conventional hydrazide-functionalized products are composed of a single layer of hydrazide functional groups. 24328033 3 16 theme surface 359:365 arg1 area 367:370 the limited specific surface area 338:370 the limited specific surface area of such a structure 338:390 Due to the limited specific surface area of such a structure, the loading amount of hydrazide groups immobilized on these materials is restricted. 24328033 5 17 theme non-crosslinked 754:768 arg1 chains 778:783 hydrazide-modified non-crosslinked polymer chains 735:783 hydrazide-modified non-crosslinked polymer chains 735:783 Here, we introduce a new functionalized magnetic nanoparticle coating with hydrazide-modified non-crosslinked polymer chains. 24328033 9 18 theme glycopeptide 1374:1385 arg1 mg 1448:1449 25 μg mg 1442:1449 25 μg mg(-1) 1442:1453 The recovery ratio of glycopeptides was determined to be 77.8%, and the glycopeptide binding capacity of the materials was determined to be 25 μg mg(-1). 24328033 9 18 theme glycopeptide 1374:1385 arg1 capacity 1395:1402 the glycopeptide binding capacity 1370:1402 the glycopeptide binding capacity of the materials 1370:1419 The recovery ratio of glycopeptides was determined to be 77.8%, and the glycopeptide binding capacity of the materials was determined to be 25 μg mg(-1). 24328033 8 19 from mixture 1191:1197 arg1 glycopeptides 1160:1172 glycopeptides 1160:1172 glycopeptides from a digestion mixture of fetuin 1160:1207 The new particles enabled the highly sensitive and selective enrichment of glycopeptides from a digestion mixture of fetuin, even from a background mixture of non-glycosylated protein that was 100-fold more abundant. 24328033 8 19 from mixture 1191:1197 arg1 enrichment 1146:1155 the highly sensitive and selective enrichment 1111:1155 the highly sensitive and selective enrichment of glycopeptides from a digestion mixture of fetuin 1111:1207 The new particles enabled the highly sensitive and selective enrichment of glycopeptides from a digestion mixture of fetuin, even from a background mixture of non-glycosylated protein that was 100-fold more abundant. 24328033 3 20 theme limited 342:348 arg1 area 367:370 the limited specific surface area 338:370 the limited specific surface area of such a structure 338:390 Due to the limited specific surface area of such a structure, the loading amount of hydrazide groups immobilized on these materials is restricted. 24328033 2 21 theme functional 312:321 arg1 groups 323:328 hydrazide functional groups 302:328 hydrazide functional groups 302:328 However, conventional hydrazide-functionalized products are composed of a single layer of hydrazide functional groups. 24328033 1 22 theme hydrazide 172:180 arg1 chemistry 182:190 hydrazide chemistry 172:190 hydrazide chemistry 172:190 Among the common approaches for global glycopeptide enrichment, hydrazide chemistry is well recognized. 24328033 10 23 link N-linked 1556:1563 arg1 glycopeptides 1565:1577 N-linked glycopeptides 1556:1577 N-linked glycopeptides from mouse liver tissues, which resulted in the assignment of 511 unique glycopeptides belonging to 372 different glycoproteins 1556:1705 Finally, the novel multivalent hydrazide-functionalized particles were applied in the enrichment of N-linked glycopeptides from mouse liver tissues, which resulted in the assignment of 511 unique glycopeptides belonging to 372 different glycoproteins. 24328033 10 24 theme glycopeptides 1565:1577 arg1 enrichment 1542:1551 the enrichment 1538:1551 the enrichment of N-linked glycopeptides from mouse liver tissues, which resulted in the assignment of 511 unique glycopeptides belonging to 372 different glycoproteins 1538:1705 Finally, the novel multivalent hydrazide-functionalized particles were applied in the enrichment of N-linked glycopeptides from mouse liver tissues, which resulted in the assignment of 511 unique glycopeptides belonging to 372 different glycoproteins. 24328033 10 25 gly glycopeptides 1652:1664 arg2 glycopeptides 1652:1664 511 unique glycopeptides 1641:1664 511 unique glycopeptides belonging to 372 different glycoproteins 1641:1705 Finally, the novel multivalent hydrazide-functionalized particles were applied in the enrichment of N-linked glycopeptides from mouse liver tissues, which resulted in the assignment of 511 unique glycopeptides belonging to 372 different glycoproteins. 24328033 8 26 theme glycopeptides 1160:1172 arg1 enrichment 1146:1155 the highly sensitive and selective enrichment 1111:1155 the highly sensitive and selective enrichment of glycopeptides from a digestion mixture of fetuin 1111:1207 The new particles enabled the highly sensitive and selective enrichment of glycopeptides from a digestion mixture of fetuin, even from a background mixture of non-glycosylated protein that was 100-fold more abundant. 24328033 3 27 theme loading 397:403 arg1 groups 425:430 hydrazide groups 415:430 hydrazide groups 415:430 Due to the limited specific surface area of such a structure, the loading amount of hydrazide groups immobilized on these materials is restricted. 24328033 3 27 theme loading 397:403 arg1 amount 405:410 the loading amount 393:410 the loading amount of hydrazide groups immobilized on these materials 393:461 Due to the limited specific surface area of such a structure, the loading amount of hydrazide groups immobilized on these materials is restricted. 24328033 10 28 theme multivalent 1475:1485 arg1 particles 1512:1520 the novel multivalent hydrazide-functionalized particles 1465:1520 the novel multivalent hydrazide-functionalized particles 1465:1520 Finally, the novel multivalent hydrazide-functionalized particles were applied in the enrichment of N-linked glycopeptides from mouse liver tissues, which resulted in the assignment of 511 unique glycopeptides belonging to 372 different glycoproteins. 24328033 6 29 theme multivalent 790:800 arg1 particles 827:835 The multivalent hydrazide-functionalized particles 786:835 The multivalent hydrazide-functionalized particles 786:835 The multivalent hydrazide-functionalized particles were synthesized by the surface-initiated atom transfer radical polymerization (SI-ATRP) technique. 24328033 7 30 theme single-layered 1059:1072 arg1 materials 1074:1082 conventional single-layered materials 1046:1082 conventional single-layered materials 1046:1082 The density of the hydrazide groups on the surface of these nanoparticles was three-fold higher than that of conventional single-layered materials. 24328033 3 31 theme groups 425:430 arg1 groups 425:430 hydrazide groups 415:430 hydrazide groups 415:430 Due to the limited specific surface area of such a structure, the loading amount of hydrazide groups immobilized on these materials is restricted. 24328033 3 31 theme groups 425:430 arg1 amount 405:410 the loading amount 393:410 the loading amount of hydrazide groups immobilized on these materials 393:461 Due to the limited specific surface area of such a structure, the loading amount of hydrazide groups immobilized on these materials is restricted. 24328033 4 32 theme limited 524:530 arg1 rate 541:544 a limited reaction rate 522:544 a limited reaction rate with glycopeptides 522:563 Therefore, these materials can only provide a limited reaction rate with glycopeptides in complex protein samples, which is exacerbated by the microheterogeneities of glycosylation. 24328033 10 33 theme mouse 1584:1588 arg1 tissues 1596:1602 mouse liver tissues 1584:1602 mouse liver tissues 1584:1602 Finally, the novel multivalent hydrazide-functionalized particles were applied in the enrichment of N-linked glycopeptides from mouse liver tissues, which resulted in the assignment of 511 unique glycopeptides belonging to 372 different glycoproteins. 24328033 0 34 theme Multivalent 0:10 arg1 nanoparticles 46:58 Multivalent hydrazide-functionalized magnetic nanoparticles 0:58 Multivalent hydrazide-functionalized magnetic nanoparticles for glycopeptide enrichment and identification 0:105 Multivalent hydrazide-functionalized magnetic nanoparticles for glycopeptide enrichment and identification. 24328033 8 35 theme fetuin 1202:1207 arg1 mixture 1191:1197 a digestion mixture 1179:1197 a digestion mixture of fetuin 1179:1207 The new particles enabled the highly sensitive and selective enrichment of glycopeptides from a digestion mixture of fetuin, even from a background mixture of non-glycosylated protein that was 100-fold more abundant. 24328033 0 36 theme magnetic 37:44 arg1 nanoparticles 46:58 Multivalent hydrazide-functionalized magnetic nanoparticles 0:58 Multivalent hydrazide-functionalized magnetic nanoparticles for glycopeptide enrichment and identification 0:105 Multivalent hydrazide-functionalized magnetic nanoparticles for glycopeptide enrichment and identification. 24328033 1 37 theme global 140:145 arg1 enrichment 160:169 global glycopeptide enrichment 140:169 global glycopeptide enrichment 140:169 Among the common approaches for global glycopeptide enrichment, hydrazide chemistry is well recognized. 24328033 7 38 from density 941:947 arg1 surface 980:986 the surface 976:986 the surface of these nanoparticles 976:1009 The density of the hydrazide groups on the surface of these nanoparticles was three-fold higher than that of conventional single-layered materials. 24328033 4 39 theme complex 568:574 arg1 samples 584:590 complex protein samples 568:590 complex protein samples 568:590 Therefore, these materials can only provide a limited reaction rate with glycopeptides in complex protein samples, which is exacerbated by the microheterogeneities of glycosylation. 24328033 6 40 theme atom 879:882 arg1 technique 926:934 the surface-initiated atom transfer radical polymerization (SI-ATRP) technique 857:934 the surface-initiated atom transfer radical polymerization (SI-ATRP) technique 857:934 The multivalent hydrazide-functionalized particles were synthesized by the surface-initiated atom transfer radical polymerization (SI-ATRP) technique. 24328033 8 41 theme non-glycosylated 1244:1259 arg1 protein 1261:1267 non-glycosylated protein 1244:1267 non-glycosylated protein that was 100-fold more abundant 1244:1299 The new particles enabled the highly sensitive and selective enrichment of glycopeptides from a digestion mixture of fetuin, even from a background mixture of non-glycosylated protein that was 100-fold more abundant. 24328033 0 42 gly glycopeptide 64:75 arg2 glycopeptide 64:75 glycopeptide enrichment 64:86 glycopeptide enrichment 64:86 Multivalent hydrazide-functionalized magnetic nanoparticles for glycopeptide enrichment and identification. 24328033 7 43 theme groups 966:971 arg1 higher 1026:1031 higher 1026:1031 higher 1026:1031 The density of the hydrazide groups on the surface of these nanoparticles was three-fold higher than that of conventional single-layered materials. 24328033 7 43 theme groups 966:971 arg1 density 941:947 The density 937:947 The density of the hydrazide groups on the surface of these nanoparticles 937:1009 The density of the hydrazide groups on the surface of these nanoparticles was three-fold higher than that of conventional single-layered materials. 24328033 2 44 theme hydrazide-functionalized 234:257 arg1 products 259:266 conventional hydrazide-functionalized products 221:266 conventional hydrazide-functionalized products 221:266 However, conventional hydrazide-functionalized products are composed of a single layer of hydrazide functional groups. 24328033 8 45 from enrichment 1146:1155 arg1 mixture 1191:1197 a digestion mixture 1179:1197 a digestion mixture of fetuin 1179:1207 The new particles enabled the highly sensitive and selective enrichment of glycopeptides from a digestion mixture of fetuin, even from a background mixture of non-glycosylated protein that was 100-fold more abundant. 24328033 10 46 theme glycopeptides 1652:1664 arg1 assignment 1627:1636 the assignment 1623:1636 the assignment of 511 unique glycopeptides belonging to 372 different glycoproteins 1623:1705 Finally, the novel multivalent hydrazide-functionalized particles were applied in the enrichment of N-linked glycopeptides from mouse liver tissues, which resulted in the assignment of 511 unique glycopeptides belonging to 372 different glycoproteins. 24328033 11 47 theme glycopeptide 1788:1799 arg1 enrichment 1801:1810 glycopeptide enrichment 1788:1810 glycopeptide enrichment in complex proteomics samples 1788:1840 The results further demonstrated the potential of the multivalent particles for glycopeptide enrichment in complex proteomics samples. 24328033 5 48 theme magnetic 700:707 arg1 coating 722:728 a new functionalized magnetic nanoparticle coating 679:728 a new functionalized magnetic nanoparticle coating with hydrazide-modified non-crosslinked polymer chains 679:783 Here, we introduce a new functionalized magnetic nanoparticle coating with hydrazide-modified non-crosslinked polymer chains. 24328033 9 49 theme recovery 1306:1313 arg1 ratio 1315:1319 The recovery ratio 1302:1319 The recovery ratio of glycopeptides 1302:1336 The recovery ratio of glycopeptides was determined to be 77.8%, and the glycopeptide binding capacity of the materials was determined to be 25 μg mg(-1). 24328033 9 49 theme recovery 1306:1313 arg1 % 1363:1363 77.8% 1359:1363 77.8% 1359:1363 The recovery ratio of glycopeptides was determined to be 77.8%, and the glycopeptide binding capacity of the materials was determined to be 25 μg mg(-1). 24328033 11 50 theme particles 1774:1782 arg1 potential 1745:1753 the potential 1741:1753 the potential of the multivalent particles for glycopeptide enrichment in complex proteomics samples 1741:1840 The results further demonstrated the potential of the multivalent particles for glycopeptide enrichment in complex proteomics samples. 24328033 10 51 theme hydrazide-functionalized 1487:1510 arg1 particles 1512:1520 the novel multivalent hydrazide-functionalized particles 1465:1520 the novel multivalent hydrazide-functionalized particles 1465:1520 Finally, the novel multivalent hydrazide-functionalized particles were applied in the enrichment of N-linked glycopeptides from mouse liver tissues, which resulted in the assignment of 511 unique glycopeptides belonging to 372 different glycoproteins. 24328033 8 52 theme sensitive 1122:1130 arg1 enrichment 1146:1155 the highly sensitive and selective enrichment 1111:1155 the highly sensitive and selective enrichment of glycopeptides from a digestion mixture of fetuin 1111:1207 The new particles enabled the highly sensitive and selective enrichment of glycopeptides from a digestion mixture of fetuin, even from a background mixture of non-glycosylated protein that was 100-fold more abundant. 24328033 10 53 theme different 1683:1691 arg1 glycoproteins 1693:1705 372 different glycoproteins 1679:1705 372 different glycoproteins 1679:1705 Finally, the novel multivalent hydrazide-functionalized particles were applied in the enrichment of N-linked glycopeptides from mouse liver tissues, which resulted in the assignment of 511 unique glycopeptides belonging to 372 different glycoproteins. 24328033 11 54 theme proteomics 1823:1832 arg1 samples 1834:1840 complex proteomics samples 1815:1840 complex proteomics samples 1815:1840 The results further demonstrated the potential of the multivalent particles for glycopeptide enrichment in complex proteomics samples. 24328033 10 55 theme novel 1469:1473 arg1 particles 1512:1520 the novel multivalent hydrazide-functionalized particles 1465:1520 the novel multivalent hydrazide-functionalized particles 1465:1520 Finally, the novel multivalent hydrazide-functionalized particles were applied in the enrichment of N-linked glycopeptides from mouse liver tissues, which resulted in the assignment of 511 unique glycopeptides belonging to 372 different glycoproteins. 24328033 8 56 theme selective 1136:1144 arg1 enrichment 1146:1155 the highly sensitive and selective enrichment 1111:1155 the highly sensitive and selective enrichment of glycopeptides from a digestion mixture of fetuin 1111:1207 The new particles enabled the highly sensitive and selective enrichment of glycopeptides from a digestion mixture of fetuin, even from a background mixture of non-glycosylated protein that was 100-fold more abundant. 24328033 5 57 theme new 681:683 arg1 coating 722:728 a new functionalized magnetic nanoparticle coating 679:728 a new functionalized magnetic nanoparticle coating with hydrazide-modified non-crosslinked polymer chains 679:783 Here, we introduce a new functionalized magnetic nanoparticle coating with hydrazide-modified non-crosslinked polymer chains. 24328033 6 58 theme radical 893:899 arg1 technique 926:934 the surface-initiated atom transfer radical polymerization (SI-ATRP) technique 857:934 the surface-initiated atom transfer radical polymerization (SI-ATRP) technique 857:934 The multivalent hydrazide-functionalized particles were synthesized by the surface-initiated atom transfer radical polymerization (SI-ATRP) technique. 24328033 7 59 theme hydrazide 956:964 arg1 groups 966:971 the hydrazide groups 952:971 the hydrazide groups 952:971 The density of the hydrazide groups on the surface of these nanoparticles was three-fold higher than that of conventional single-layered materials. 24328033 9 60 gly glycopeptides 1324:1336 arg2 glycopeptides 1324:1336 glycopeptides 1324:1336 glycopeptides 1324:1336 The recovery ratio of glycopeptides was determined to be 77.8%, and the glycopeptide binding capacity of the materials was determined to be 25 μg mg(-1). 24328033 9 61 gly glycopeptide 1374:1385 arg2 glycopeptide 1374:1385 the glycopeptide binding capacity 1370:1402 the glycopeptide binding capacity of the materials 1370:1419 The recovery ratio of glycopeptides was determined to be 77.8%, and the glycopeptide binding capacity of the materials was determined to be 25 μg mg(-1). 24328033 10 62 gly glycoproteins 1693:1705 arg1 glycoproteins 1693:1705 372 different glycoproteins 1679:1705 372 different glycoproteins 1679:1705 Finally, the novel multivalent hydrazide-functionalized particles were applied in the enrichment of N-linked glycopeptides from mouse liver tissues, which resulted in the assignment of 511 unique glycopeptides belonging to 372 different glycoproteins. 24328033 5 63 theme hydrazide-modified 735:752 arg1 chains 778:783 hydrazide-modified non-crosslinked polymer chains 735:783 hydrazide-modified non-crosslinked polymer chains 735:783 Here, we introduce a new functionalized magnetic nanoparticle coating with hydrazide-modified non-crosslinked polymer chains. 24328033 1 64 theme glycopeptide 147:158 arg1 enrichment 160:169 global glycopeptide enrichment 140:169 global glycopeptide enrichment 140:169 Among the common approaches for global glycopeptide enrichment, hydrazide chemistry is well recognized. 24328033 10 65 from tissues 1596:1602 arg1 enrichment 1542:1551 the enrichment 1538:1551 the enrichment of N-linked glycopeptides from mouse liver tissues, which resulted in the assignment of 511 unique glycopeptides belonging to 372 different glycoproteins 1538:1705 Finally, the novel multivalent hydrazide-functionalized particles were applied in the enrichment of N-linked glycopeptides from mouse liver tissues, which resulted in the assignment of 511 unique glycopeptides belonging to 372 different glycoproteins. 24328033 10 65 from tissues 1596:1602 arg1 glycopeptides 1565:1577 N-linked glycopeptides 1556:1577 N-linked glycopeptides from mouse liver tissues, which resulted in the assignment of 511 unique glycopeptides belonging to 372 different glycoproteins 1556:1705 Finally, the novel multivalent hydrazide-functionalized particles were applied in the enrichment of N-linked glycopeptides from mouse liver tissues, which resulted in the assignment of 511 unique glycopeptides belonging to 372 different glycoproteins. 24328033 8 66 gly glycopeptides 1160:1172 arg2 glycopeptides 1160:1172 glycopeptides 1160:1172 glycopeptides from a digestion mixture of fetuin 1160:1207 The new particles enabled the highly sensitive and selective enrichment of glycopeptides from a digestion mixture of fetuin, even from a background mixture of non-glycosylated protein that was 100-fold more abundant. 24328033 8 66 gly glycopeptides 1160:1172 arg1 mixture 1191:1197 a digestion mixture 1179:1197 a digestion mixture of fetuin 1179:1207 The new particles enabled the highly sensitive and selective enrichment of glycopeptides from a digestion mixture of fetuin, even from a background mixture of non-glycosylated protein that was 100-fold more abundant. 24328033 5 67 theme polymer 770:776 arg1 chains 778:783 hydrazide-modified non-crosslinked polymer chains 735:783 hydrazide-modified non-crosslinked polymer chains 735:783 Here, we introduce a new functionalized magnetic nanoparticle coating with hydrazide-modified non-crosslinked polymer chains. 24328033 9 68 theme binding 1387:1393 arg1 mg 1448:1449 25 μg mg 1442:1449 25 μg mg(-1) 1442:1453 The recovery ratio of glycopeptides was determined to be 77.8%, and the glycopeptide binding capacity of the materials was determined to be 25 μg mg(-1). 24328033 9 68 theme binding 1387:1393 arg1 capacity 1395:1402 the glycopeptide binding capacity 1370:1402 the glycopeptide binding capacity of the materials 1370:1419 The recovery ratio of glycopeptides was determined to be 77.8%, and the glycopeptide binding capacity of the materials was determined to be 25 μg mg(-1). 24328033 2 69 theme groups 323:328 arg1 layer 293:297 a single layer 284:297 a single layer of hydrazide functional groups 284:328 However, conventional hydrazide-functionalized products are composed of a single layer of hydrazide functional groups. 24328033 3 70 theme specific 350:357 arg1 area 367:370 the limited specific surface area 338:370 the limited specific surface area of such a structure 338:390 Due to the limited specific surface area of such a structure, the loading amount of hydrazide groups immobilized on these materials is restricted. 24328033 2 71 theme hydrazide 302:310 arg1 groups 323:328 hydrazide functional groups 302:328 hydrazide functional groups 302:328 However, conventional hydrazide-functionalized products are composed of a single layer of hydrazide functional groups. 24328033 3 72 theme structure 382:390 arg1 area 367:370 the limited specific surface area 338:370 the limited specific surface area of such a structure 338:390 Due to the limited specific surface area of such a structure, the loading amount of hydrazide groups immobilized on these materials is restricted. 24328033 9 73 theme materials 1411:1419 arg1 mg 1448:1449 25 μg mg 1442:1449 25 μg mg(-1) 1442:1453 The recovery ratio of glycopeptides was determined to be 77.8%, and the glycopeptide binding capacity of the materials was determined to be 25 μg mg(-1). 24328033 9 73 theme materials 1411:1419 arg1 capacity 1395:1402 the glycopeptide binding capacity 1370:1402 the glycopeptide binding capacity of the materials 1370:1419 The recovery ratio of glycopeptides was determined to be 77.8%, and the glycopeptide binding capacity of the materials was determined to be 25 μg mg(-1). 24328033 10 74 theme N-linked 1556:1563 arg1 glycopeptides 1565:1577 N-linked glycopeptides 1556:1577 N-linked glycopeptides from mouse liver tissues, which resulted in the assignment of 511 unique glycopeptides belonging to 372 different glycoproteins 1556:1705 Finally, the novel multivalent hydrazide-functionalized particles were applied in the enrichment of N-linked glycopeptides from mouse liver tissues, which resulted in the assignment of 511 unique glycopeptides belonging to 372 different glycoproteins. 24328033 8 75 theme digestion 1181:1189 arg1 mixture 1191:1197 a digestion mixture 1179:1197 a digestion mixture of fetuin 1179:1207 The new particles enabled the highly sensitive and selective enrichment of glycopeptides from a digestion mixture of fetuin, even from a background mixture of non-glycosylated protein that was 100-fold more abundant. 24328033 6 76 theme hydrazide-functionalized 802:825 arg1 particles 827:835 The multivalent hydrazide-functionalized particles 786:835 The multivalent hydrazide-functionalized particles 786:835 The multivalent hydrazide-functionalized particles were synthesized by the surface-initiated atom transfer radical polymerization (SI-ATRP) technique. 24328033 5 77 link non-crosslinked 754:768 arg1 chains 778:783 hydrazide-modified non-crosslinked polymer chains 735:783 hydrazide-modified non-crosslinked polymer chains 735:783 Here, we introduce a new functionalized magnetic nanoparticle coating with hydrazide-modified non-crosslinked polymer chains. 24328033 4 78 theme reaction 532:539 arg1 rate 541:544 a limited reaction rate 522:544 a limited reaction rate with glycopeptides 522:563 Therefore, these materials can only provide a limited reaction rate with glycopeptides in complex protein samples, which is exacerbated by the microheterogeneities of glycosylation. 24328033 10 79 theme liver 1590:1594 arg1 tissues 1596:1602 mouse liver tissues 1584:1602 mouse liver tissues 1584:1602 Finally, the novel multivalent hydrazide-functionalized particles were applied in the enrichment of N-linked glycopeptides from mouse liver tissues, which resulted in the assignment of 511 unique glycopeptides belonging to 372 different glycoproteins. 24328033 0 80 theme hydrazide-functionalized 12:35 arg1 nanoparticles 46:58 Multivalent hydrazide-functionalized magnetic nanoparticles 0:58 Multivalent hydrazide-functionalized magnetic nanoparticles for glycopeptide enrichment and identification 0:105 Multivalent hydrazide-functionalized magnetic nanoparticles for glycopeptide enrichment and identification. 24328033 9 81 theme μg 1445:1446 arg1 -1 1451:1452 -1 1451:1452 -1 1451:1452 The recovery ratio of glycopeptides was determined to be 77.8%, and the glycopeptide binding capacity of the materials was determined to be 25 μg mg(-1). 24328033 9 81 theme μg 1445:1446 arg1 mg 1448:1449 25 μg mg 1442:1449 25 μg mg(-1) 1442:1453 The recovery ratio of glycopeptides was determined to be 77.8%, and the glycopeptide binding capacity of the materials was determined to be 25 μg mg(-1). 24328033 9 81 theme μg 1445:1446 arg1 capacity 1395:1402 the glycopeptide binding capacity 1370:1402 the glycopeptide binding capacity of the materials 1370:1419 The recovery ratio of glycopeptides was determined to be 77.8%, and the glycopeptide binding capacity of the materials was determined to be 25 μg mg(-1). 24328033 1 82 theme common 118:123 arg1 approaches 125:134 the common approaches 114:134 the common approaches for global glycopeptide enrichment 114:169 Among the common approaches for global glycopeptide enrichment, hydrazide chemistry is well recognized. 24328033 7 83 theme conventional 1046:1057 arg1 materials 1074:1082 conventional single-layered materials 1046:1082 conventional single-layered materials 1046:1082 The density of the hydrazide groups on the surface of these nanoparticles was three-fold higher than that of conventional single-layered materials. 24328033 3 84 theme hydrazide 415:423 arg1 groups 425:430 hydrazide groups 415:430 hydrazide groups 415:430 Due to the limited specific surface area of such a structure, the loading amount of hydrazide groups immobilized on these materials is restricted. 24328033 2 85 theme conventional 221:232 arg1 products 259:266 conventional hydrazide-functionalized products 221:266 conventional hydrazide-functionalized products 221:266 However, conventional hydrazide-functionalized products are composed of a single layer of hydrazide functional groups. 24328033 8 86 gly non-glycosylated 1244:1259 arg1 protein 1261:1267 non-glycosylated protein 1244:1267 non-glycosylated protein that was 100-fold more abundant 1244:1299 The new particles enabled the highly sensitive and selective enrichment of glycopeptides from a digestion mixture of fetuin, even from a background mixture of non-glycosylated protein that was 100-fold more abundant. 24328033 0 87 theme glycopeptide 64:75 arg1 enrichment 77:86 glycopeptide enrichment 64:86 glycopeptide enrichment 64:86 Multivalent hydrazide-functionalized magnetic nanoparticles for glycopeptide enrichment and identification. 24328033 8 88 theme background 1222:1231 arg1 mixture 1233:1239 a background mixture 1220:1239 a background mixture of non-glycosylated protein that was 100-fold more abundant 1220:1299 The new particles enabled the highly sensitive and selective enrichment of glycopeptides from a digestion mixture of fetuin, even from a background mixture of non-glycosylated protein that was 100-fold more abundant. 24328033 4 89 theme protein 576:582 arg1 samples 584:590 complex protein samples 568:590 complex protein samples 568:590 Therefore, these materials can only provide a limited reaction rate with glycopeptides in complex protein samples, which is exacerbated by the microheterogeneities of glycosylation. 24328033 6 90 theme transfer 884:891 arg1 technique 926:934 the surface-initiated atom transfer radical polymerization (SI-ATRP) technique 857:934 the surface-initiated atom transfer radical polymerization (SI-ATRP) technique 857:934 The multivalent hydrazide-functionalized particles were synthesized by the surface-initiated atom transfer radical polymerization (SI-ATRP) technique. 24328033 6 91 theme surface-initiated 861:877 arg1 technique 926:934 the surface-initiated atom transfer radical polymerization (SI-ATRP) technique 857:934 the surface-initiated atom transfer radical polymerization (SI-ATRP) technique 857:934 The multivalent hydrazide-functionalized particles were synthesized by the surface-initiated atom transfer radical polymerization (SI-ATRP) technique. 24328033 8 92 theme protein 1261:1267 arg1 mixture 1233:1239 a background mixture 1220:1239 a background mixture of non-glycosylated protein that was 100-fold more abundant 1220:1299 The new particles enabled the highly sensitive and selective enrichment of glycopeptides from a digestion mixture of fetuin, even from a background mixture of non-glycosylated protein that was 100-fold more abundant. 24328033 4 93 with rate 541:544 arg1 glycopeptides 551:563 glycopeptides 551:563 glycopeptides 551:563 Therefore, these materials can only provide a limited reaction rate with glycopeptides in complex protein samples, which is exacerbated by the microheterogeneities of glycosylation. 24328033 5 94 with coating 722:728 arg1 chains 778:783 hydrazide-modified non-crosslinked polymer chains 735:783 hydrazide-modified non-crosslinked polymer chains 735:783 Here, we introduce a new functionalized magnetic nanoparticle coating with hydrazide-modified non-crosslinked polymer chains. 24328033 11 95 from enrichment 1801:1810 arg1 samples 1834:1840 complex proteomics samples 1815:1840 complex proteomics samples 1815:1840 The results further demonstrated the potential of the multivalent particles for glycopeptide enrichment in complex proteomics samples. 24328033 7 96 theme nanoparticles 997:1009 arg1 surface 980:986 the surface 976:986 the surface of these nanoparticles 976:1009 The density of the hydrazide groups on the surface of these nanoparticles was three-fold higher than that of conventional single-layered materials. 28944095 2 0 theme numerous 360:367 arg1 cases 369:373 numerous cases 360:373 numerous cases of intracellular Ig crystallization 360:409 However, numerous cases of intracellular Ig crystallization are reported in plasma cell dyscrasias. 28944095 5 1 from inclusions 1024:1033 arg1 cells 1057:1061 transfected HEK293 cells 1038:1061 transfected HEK293 cells 1038:1061 By testing various subunit combinations through mixing and matching of individual subunit chains derived from a panel of human IgG clones, we identified one secretion competent IgG2λ that induced needle-like crystalline inclusions in transfected HEK293 cells. 28944095 3 2 theme biological 559:568 arg1 requirements 570:581 the biochemical and cell biological requirements 534:581 the biochemical and cell biological requirements for this cryptic event 534:604 What makes some Ig clones more prone to crystallize during biosynthesis as well as the biochemical and cell biological requirements for this cryptic event are poorly understood. 28944095 1 3 theme large 288:292 arg1 size 294:297 their large size 282:297 their large size 282:297 Full-length immunoglobulins (Igs) are widely considered difficult to crystallize because of their large size, N-linked glycosylation, and flexible hinge region. 28944095 4 4 theme crystallization 687:701 arg1 process 659:665 the underlying process 644:665 the underlying process of intracellular Ig crystallization 644:701 To investigate the underlying process of intracellular Ig crystallization we searched for model IgGs that can induce crystalline inclusions during recombinant overexpression. 28944095 7 5 theme patch 1293:1297 arg1 presence 1250:1257 the presence 1246:1257 the presence of a prominent negatively-charged patch on the variable domain surface 1246:1328 Homology modeling revealed the presence of a prominent negatively-charged patch on the variable domain surface. 28944095 1 6 theme Full-length 190:200 arg1 immunoglobulins 202:216 Full-length immunoglobulins 190:216 Full-length immunoglobulins (Igs) 190:222 Full-length immunoglobulins (Igs) are widely considered difficult to crystallize because of their large size, N-linked glycosylation, and flexible hinge region. 28944095 1 6 theme Full-length 190:200 arg1 Igs 219:221 Igs 219:221 Igs 219:221 Full-length immunoglobulins (Igs) are widely considered difficult to crystallize because of their large size, N-linked glycosylation, and flexible hinge region. 28944095 10 7 theme patch 1702:1706 arg1 IgG1 1655:1658 IgG1 1655:1658 IgG1 1655:1658 Furthermore, subtype switching from IgG2 to IgG1 and stepwise neutralization of the acidic patch independently abrogated Ig crystallization events. 28944095 10 7 theme patch 1702:1706 arg1 neutralization 1673:1686 stepwise neutralization 1664:1686 stepwise neutralization 1664:1686 Furthermore, subtype switching from IgG2 to IgG1 and stepwise neutralization of the acidic patch independently abrogated Ig crystallization events. 28944095 3 8 theme cryptic 592:598 arg1 event 600:604 this cryptic event 587:604 this cryptic event 587:604 What makes some Ig clones more prone to crystallize during biosynthesis as well as the biochemical and cell biological requirements for this cryptic event are poorly understood. 28944095 5 9 theme IgG 931:933 arg1 clones 935:940 human IgG clones 925:940 human IgG clones 925:940 By testing various subunit combinations through mixing and matching of individual subunit chains derived from a panel of human IgG clones, we identified one secretion competent IgG2λ that induced needle-like crystalline inclusions in transfected HEK293 cells. 28944095 8 10 theme acids 1372:1376 arg1 chain 1461:1465 the light chain 1451:1465 the light chain 1451:1465 The patch was composed of eight aspartic acids, of which five were in the heavy chain variable region and three were in the light chain. 28944095 0 11 theme crystalline 123:133 arg1 formation 150:158 crystalline inclusion body formation 123:158 crystalline inclusion body formation 123:158 Intermolecular interactions involving an acidic patch on immunoglobulin variable domain and the γ2 constant region mediate crystalline inclusion body formation in the endoplasmic reticulum. 28944095 5 12 theme secretion 961:969 arg1 IgG2λ 981:985 one secretion competent IgG2λ 957:985 one secretion competent IgG2λ that induced needle-like crystalline inclusions in transfected HEK293 cells 957:1061 By testing various subunit combinations through mixing and matching of individual subunit chains derived from a panel of human IgG clones, we identified one secretion competent IgG2λ that induced needle-like crystalline inclusions in transfected HEK293 cells. 28944095 4 13 theme intracellular 670:682 arg1 crystallization 687:701 intracellular Ig crystallization 670:701 intracellular Ig crystallization 670:701 To investigate the underlying process of intracellular Ig crystallization we searched for model IgGs that can induce crystalline inclusions during recombinant overexpression. 28944095 10 14 theme crystallization 1735:1749 arg1 events 1751:1756 Ig crystallization events 1732:1756 Ig crystallization events 1732:1756 Furthermore, subtype switching from IgG2 to IgG1 and stepwise neutralization of the acidic patch independently abrogated Ig crystallization events. 28944095 11 15 theme γ2 1975:1976 arg1 region 1995:2000 the γ2 subunit constant region 1971:2000 the γ2 subunit constant region 1971:2000 The evidence supported that the formation of needle-like crystalline inclusions in the ER was underscored by multivalent intermolecular interactions between the acidic patch and undefined determinants present on the γ2 subunit constant region. 28944095 0 16 theme body 145:148 arg1 formation 150:158 crystalline inclusion body formation 123:158 crystalline inclusion body formation 123:158 Intermolecular interactions involving an acidic patch on immunoglobulin variable domain and the γ2 constant region mediate crystalline inclusion body formation in the endoplasmic reticulum. 28944095 9 17 theme resident 1592:1599 arg1 proteins 1601:1608 ER resident proteins 1589:1608 ER resident proteins 1589:1608 Crystallization occurred only when the two subunits were co-transfected and the intracellular crystals co-localized with ER resident proteins. 28944095 11 18 theme intermolecular 1880:1893 arg1 interactions 1895:1906 multivalent intermolecular interactions 1868:1906 multivalent intermolecular interactions between the acidic patch and undefined determinants present on the γ2 subunit constant region 1868:2000 The evidence supported that the formation of needle-like crystalline inclusions in the ER was underscored by multivalent intermolecular interactions between the acidic patch and undefined determinants present on the γ2 subunit constant region. 28944095 0 19 theme endoplasmic 167:177 arg1 reticulum 179:187 the endoplasmic reticulum 163:187 the endoplasmic reticulum 163:187 Intermolecular interactions involving an acidic patch on immunoglobulin variable domain and the γ2 constant region mediate crystalline inclusion body formation in the endoplasmic reticulum. 28944095 4 20 theme model 719:723 arg1 IgGs 725:728 model IgGs 719:728 model IgGs that can induce crystalline inclusions during recombinant overexpression 719:801 To investigate the underlying process of intracellular Ig crystallization we searched for model IgGs that can induce crystalline inclusions during recombinant overexpression. 28944095 0 21 theme variable 72:79 arg1 domain 81:86 immunoglobulin variable domain 57:86 immunoglobulin variable domain 57:86 Intermolecular interactions involving an acidic patch on immunoglobulin variable domain and the γ2 constant region mediate crystalline inclusion body formation in the endoplasmic reticulum. 28944095 7 22 theme prominent 1264:1272 arg1 patch 1293:1297 a prominent negatively-charged patch 1262:1297 a prominent negatively-charged patch 1262:1297 Homology modeling revealed the presence of a prominent negatively-charged patch on the variable domain surface. 28944095 8 23 theme variable 1417:1424 arg1 region 1426:1431 the heavy chain variable region 1401:1431 the heavy chain variable region 1401:1431 The patch was composed of eight aspartic acids, of which five were in the heavy chain variable region and three were in the light chain. 28944095 11 24 theme acidic 1920:1925 arg1 determinants 1947:1958 the acidic patch and undefined determinants 1916:1958 the acidic patch and undefined determinants present on the γ2 subunit constant region 1916:2000 The evidence supported that the formation of needle-like crystalline inclusions in the ER was underscored by multivalent intermolecular interactions between the acidic patch and undefined determinants present on the γ2 subunit constant region. 28944095 5 25 theme subunit 823:829 arg1 combinations 831:842 various subunit combinations 815:842 various subunit combinations 815:842 By testing various subunit combinations through mixing and matching of individual subunit chains derived from a panel of human IgG clones, we identified one secretion competent IgG2λ that induced needle-like crystalline inclusions in transfected HEK293 cells. 28944095 6 26 theme Ig 1064:1065 arg1 crystallization 1067:1081 Ig crystallization 1064:1081 Ig crystallization 1064:1081 Ig crystallization rarely occurred at steady-state cell growth conditions but was easily induced when ER-to-Golgi transport was pharmacologically blocked. 28944095 7 27 attach presence 1250:1257 arg2 patch 1293:1297 a prominent negatively-charged patch 1262:1297 a prominent negatively-charged patch 1262:1297 Homology modeling revealed the presence of a prominent negatively-charged patch on the variable domain surface. 28944095 7 27 attach presence 1250:1257 arg1 surface 1322:1328 the variable domain surface 1302:1328 the variable domain surface 1302:1328 Homology modeling revealed the presence of a prominent negatively-charged patch on the variable domain surface. 28944095 0 28 theme γ2 96:97 arg1 region 108:113 the γ2 constant region 92:113 the γ2 constant region 92:113 Intermolecular interactions involving an acidic patch on immunoglobulin variable domain and the γ2 constant region mediate crystalline inclusion body formation in the endoplasmic reticulum. 28944095 3 29 dep crystallize 491:501 arg1 prone 482:486 prone 482:486 prone 482:486 What makes some Ig clones more prone to crystallize during biosynthesis as well as the biochemical and cell biological requirements for this cryptic event are poorly understood. 28944095 11 30 attach present 1960:1966 arg1 region 1995:2000 the γ2 subunit constant region 1971:2000 the γ2 subunit constant region 1971:2000 The evidence supported that the formation of needle-like crystalline inclusions in the ER was underscored by multivalent intermolecular interactions between the acidic patch and undefined determinants present on the γ2 subunit constant region. 28944095 11 30 attach present 1960:1966 arg2 determinants 1947:1958 the acidic patch and undefined determinants 1916:1958 the acidic patch and undefined determinants present on the γ2 subunit constant region 1916:2000 The evidence supported that the formation of needle-like crystalline inclusions in the ER was underscored by multivalent intermolecular interactions between the acidic patch and undefined determinants present on the γ2 subunit constant region. 28944095 5 31 theme HEK293 1050:1055 arg1 cells 1057:1061 transfected HEK293 cells 1038:1061 transfected HEK293 cells 1038:1061 By testing various subunit combinations through mixing and matching of individual subunit chains derived from a panel of human IgG clones, we identified one secretion competent IgG2λ that induced needle-like crystalline inclusions in transfected HEK293 cells. 28944095 4 32 theme recombinant 776:786 arg1 overexpression 788:801 recombinant overexpression 776:801 recombinant overexpression 776:801 To investigate the underlying process of intracellular Ig crystallization we searched for model IgGs that can induce crystalline inclusions during recombinant overexpression. 28944095 2 33 theme crystallization 395:409 arg1 cases 369:373 numerous cases 360:373 numerous cases of intracellular Ig crystallization 360:409 However, numerous cases of intracellular Ig crystallization are reported in plasma cell dyscrasias. 28944095 0 34 theme Intermolecular 0:13 arg1 interactions 15:26 Intermolecular interactions 0:26 Intermolecular interactions involving an acidic patch on immunoglobulin variable domain and the γ2 constant region 0:113 Intermolecular interactions involving an acidic patch on immunoglobulin variable domain and the γ2 constant region mediate crystalline inclusion body formation in the endoplasmic reticulum. 28944095 11 35 from formation 1791:1799 arg1 ER 1846:1847 the ER 1842:1847 the ER 1842:1847 The evidence supported that the formation of needle-like crystalline inclusions in the ER was underscored by multivalent intermolecular interactions between the acidic patch and undefined determinants present on the γ2 subunit constant region. 28944095 5 36 theme subunit 886:892 arg1 chains 894:899 individual subunit chains 875:899 individual subunit chains derived from a panel of human IgG clones 875:940 By testing various subunit combinations through mixing and matching of individual subunit chains derived from a panel of human IgG clones, we identified one secretion competent IgG2λ that induced needle-like crystalline inclusions in transfected HEK293 cells. 28944095 1 37 theme N-linked 300:307 arg1 glycosylation 309:321 N-linked glycosylation 300:321 N-linked glycosylation 300:321 Full-length immunoglobulins (Igs) are widely considered difficult to crystallize because of their large size, N-linked glycosylation, and flexible hinge region. 28944095 10 38 from IgG2 1647:1650 arg1 switching 1632:1640 subtype switching 1624:1640 subtype switching from IgG2 to IgG1 and stepwise neutralization of the acidic patch 1624:1706 Furthermore, subtype switching from IgG2 to IgG1 and stepwise neutralization of the acidic patch independently abrogated Ig crystallization events. 28944095 5 39 theme crystalline 1012:1022 arg1 inclusions 1024:1033 needle-like crystalline inclusions 1000:1033 needle-like crystalline inclusions in transfected HEK293 cells 1000:1061 By testing various subunit combinations through mixing and matching of individual subunit chains derived from a panel of human IgG clones, we identified one secretion competent IgG2λ that induced needle-like crystalline inclusions in transfected HEK293 cells. 28944095 8 40 theme heavy 1405:1409 arg1 region 1426:1431 the heavy chain variable region 1401:1431 the heavy chain variable region 1401:1431 The patch was composed of eight aspartic acids, of which five were in the heavy chain variable region and three were in the light chain. 28944095 2 41 theme plasma 427:432 arg1 dyscrasias 439:448 plasma cell dyscrasias 427:448 plasma cell dyscrasias 427:448 However, numerous cases of intracellular Ig crystallization are reported in plasma cell dyscrasias. 28944095 3 42 theme Ig 467:468 arg1 clones 470:475 some Ig clones 462:475 some Ig clones 462:475 What makes some Ig clones more prone to crystallize during biosynthesis as well as the biochemical and cell biological requirements for this cryptic event are poorly understood. 28944095 0 43 theme acidic 41:46 arg1 patch 48:52 an acidic patch 38:52 an acidic patch on immunoglobulin variable domain and the γ2 constant region 38:113 Intermolecular interactions involving an acidic patch on immunoglobulin variable domain and the γ2 constant region mediate crystalline inclusion body formation in the endoplasmic reticulum. 28944095 6 44 theme cell 1115:1118 arg1 conditions 1127:1136 steady-state cell growth conditions 1102:1136 steady-state cell growth conditions 1102:1136 Ig crystallization rarely occurred at steady-state cell growth conditions but was easily induced when ER-to-Golgi transport was pharmacologically blocked. 28944095 11 45 theme crystalline 1816:1826 arg1 inclusions 1828:1837 needle-like crystalline inclusions 1804:1837 needle-like crystalline inclusions 1804:1837 The evidence supported that the formation of needle-like crystalline inclusions in the ER was underscored by multivalent intermolecular interactions between the acidic patch and undefined determinants present on the γ2 subunit constant region. 28944095 1 46 theme flexible 328:335 arg1 region 343:348 flexible hinge region 328:348 flexible hinge region 328:348 Full-length immunoglobulins (Igs) are widely considered difficult to crystallize because of their large size, N-linked glycosylation, and flexible hinge region. 28944095 5 47 attach derived 901:907 arg2 chains 894:899 individual subunit chains 875:899 individual subunit chains derived from a panel of human IgG clones 875:940 By testing various subunit combinations through mixing and matching of individual subunit chains derived from a panel of human IgG clones, we identified one secretion competent IgG2λ that induced needle-like crystalline inclusions in transfected HEK293 cells. 28944095 5 47 attach derived 901:907 arg1 panel 916:920 a panel 914:920 a panel of human IgG clones 914:940 By testing various subunit combinations through mixing and matching of individual subunit chains derived from a panel of human IgG clones, we identified one secretion competent IgG2λ that induced needle-like crystalline inclusions in transfected HEK293 cells. 28944095 11 48 theme constant 1986:1993 arg1 region 1995:2000 the γ2 subunit constant region 1971:2000 the γ2 subunit constant region 1971:2000 The evidence supported that the formation of needle-like crystalline inclusions in the ER was underscored by multivalent intermolecular interactions between the acidic patch and undefined determinants present on the γ2 subunit constant region. 28944095 2 49 theme intracellular 378:390 arg1 crystallization 395:409 intracellular Ig crystallization 378:409 intracellular Ig crystallization 378:409 However, numerous cases of intracellular Ig crystallization are reported in plasma cell dyscrasias. 28944095 11 50 theme multivalent 1868:1878 arg1 interactions 1895:1906 multivalent intermolecular interactions 1868:1906 multivalent intermolecular interactions between the acidic patch and undefined determinants present on the γ2 subunit constant region 1868:2000 The evidence supported that the formation of needle-like crystalline inclusions in the ER was underscored by multivalent intermolecular interactions between the acidic patch and undefined determinants present on the γ2 subunit constant region. 28944095 7 51 theme Homology 1219:1226 arg1 modeling 1228:1235 Homology modeling 1219:1235 Homology modeling 1219:1235 Homology modeling revealed the presence of a prominent negatively-charged patch on the variable domain surface. 28944095 6 52 theme ER-to-Golgi 1166:1176 arg1 transport 1178:1186 ER-to-Golgi transport 1166:1186 ER-to-Golgi transport 1166:1186 Ig crystallization rarely occurred at steady-state cell growth conditions but was easily induced when ER-to-Golgi transport was pharmacologically blocked. 28944095 10 53 theme stepwise 1664:1671 arg1 neutralization 1673:1686 stepwise neutralization 1664:1686 stepwise neutralization 1664:1686 Furthermore, subtype switching from IgG2 to IgG1 and stepwise neutralization of the acidic patch independently abrogated Ig crystallization events. 28944095 3 54 theme biochemical 538:548 arg1 requirements 570:581 the biochemical and cell biological requirements 534:581 the biochemical and cell biological requirements for this cryptic event 534:604 What makes some Ig clones more prone to crystallize during biosynthesis as well as the biochemical and cell biological requirements for this cryptic event are poorly understood. 28944095 4 55 theme Ig 684:685 arg1 crystallization 687:701 intracellular Ig crystallization 670:701 intracellular Ig crystallization 670:701 To investigate the underlying process of intracellular Ig crystallization we searched for model IgGs that can induce crystalline inclusions during recombinant overexpression. 28944095 5 56 theme human 925:929 arg1 clones 935:940 human IgG clones 925:940 human IgG clones 925:940 By testing various subunit combinations through mixing and matching of individual subunit chains derived from a panel of human IgG clones, we identified one secretion competent IgG2λ that induced needle-like crystalline inclusions in transfected HEK293 cells. 28944095 10 57 theme acidic 1695:1700 arg1 patch 1702:1706 the acidic patch 1691:1706 the acidic patch 1691:1706 Furthermore, subtype switching from IgG2 to IgG1 and stepwise neutralization of the acidic patch independently abrogated Ig crystallization events. 28944095 11 58 theme present 1960:1966 arg1 determinants 1947:1958 the acidic patch and undefined determinants 1916:1958 the acidic patch and undefined determinants present on the γ2 subunit constant region 1916:2000 The evidence supported that the formation of needle-like crystalline inclusions in the ER was underscored by multivalent intermolecular interactions between the acidic patch and undefined determinants present on the γ2 subunit constant region. 28944095 0 59 theme inclusion 135:143 arg1 formation 150:158 crystalline inclusion body formation 123:158 crystalline inclusion body formation 123:158 Intermolecular interactions involving an acidic patch on immunoglobulin variable domain and the γ2 constant region mediate crystalline inclusion body formation in the endoplasmic reticulum. 28944095 9 60 theme intracellular 1548:1560 arg1 crystals 1562:1569 the intracellular crystals 1544:1569 the intracellular crystals 1544:1569 Crystallization occurred only when the two subunits were co-transfected and the intracellular crystals co-localized with ER resident proteins. 28944095 4 61 theme underlying 648:657 arg1 process 659:665 the underlying process 644:665 the underlying process of intracellular Ig crystallization 644:701 To investigate the underlying process of intracellular Ig crystallization we searched for model IgGs that can induce crystalline inclusions during recombinant overexpression. 28944095 11 62 theme undefined 1937:1945 arg1 determinants 1947:1958 the acidic patch and undefined determinants 1916:1958 the acidic patch and undefined determinants present on the γ2 subunit constant region 1916:2000 The evidence supported that the formation of needle-like crystalline inclusions in the ER was underscored by multivalent intermolecular interactions between the acidic patch and undefined determinants present on the γ2 subunit constant region. 28944095 10 63 theme Ig 1732:1733 arg1 events 1751:1756 Ig crystallization events 1732:1756 Ig crystallization events 1732:1756 Furthermore, subtype switching from IgG2 to IgG1 and stepwise neutralization of the acidic patch independently abrogated Ig crystallization events. 28944095 7 64 theme variable 1306:1313 arg1 surface 1322:1328 the variable domain surface 1302:1328 the variable domain surface 1302:1328 Homology modeling revealed the presence of a prominent negatively-charged patch on the variable domain surface. 28944095 9 65 theme ER 1589:1590 arg1 proteins 1601:1608 ER resident proteins 1589:1608 ER resident proteins 1589:1608 Crystallization occurred only when the two subunits were co-transfected and the intracellular crystals co-localized with ER resident proteins. 28944095 5 66 theme competent 971:979 arg1 IgG2λ 981:985 one secretion competent IgG2λ 957:985 one secretion competent IgG2λ that induced needle-like crystalline inclusions in transfected HEK293 cells 957:1061 By testing various subunit combinations through mixing and matching of individual subunit chains derived from a panel of human IgG clones, we identified one secretion competent IgG2λ that induced needle-like crystalline inclusions in transfected HEK293 cells. 28944095 6 67 theme steady-state 1102:1113 arg1 conditions 1127:1136 steady-state cell growth conditions 1102:1136 steady-state cell growth conditions 1102:1136 Ig crystallization rarely occurred at steady-state cell growth conditions but was easily induced when ER-to-Golgi transport was pharmacologically blocked. 28944095 4 68 theme crystalline 746:756 arg1 inclusions 758:767 crystalline inclusions 746:767 crystalline inclusions 746:767 To investigate the underlying process of intracellular Ig crystallization we searched for model IgGs that can induce crystalline inclusions during recombinant overexpression. 28944095 5 69 theme chains 894:899 arg1 mixing 852:857 mixing 852:857 mixing 852:857 By testing various subunit combinations through mixing and matching of individual subunit chains derived from a panel of human IgG clones, we identified one secretion competent IgG2λ that induced needle-like crystalline inclusions in transfected HEK293 cells. 28944095 5 70 theme clones 935:940 arg1 panel 916:920 a panel 914:920 a panel of human IgG clones 914:940 By testing various subunit combinations through mixing and matching of individual subunit chains derived from a panel of human IgG clones, we identified one secretion competent IgG2λ that induced needle-like crystalline inclusions in transfected HEK293 cells. 28944095 7 71 theme domain 1315:1320 arg1 surface 1322:1328 the variable domain surface 1302:1328 the variable domain surface 1302:1328 Homology modeling revealed the presence of a prominent negatively-charged patch on the variable domain surface. 28944095 5 72 theme various 815:821 arg1 combinations 831:842 various subunit combinations 815:842 various subunit combinations 815:842 By testing various subunit combinations through mixing and matching of individual subunit chains derived from a panel of human IgG clones, we identified one secretion competent IgG2λ that induced needle-like crystalline inclusions in transfected HEK293 cells. 28944095 7 73 from presence 1250:1257 arg1 surface 1322:1328 the variable domain surface 1302:1328 the variable domain surface 1302:1328 Homology modeling revealed the presence of a prominent negatively-charged patch on the variable domain surface. 28944095 8 74 theme chain 1411:1415 arg1 region 1426:1431 the heavy chain variable region 1401:1431 the heavy chain variable region 1401:1431 The patch was composed of eight aspartic acids, of which five were in the heavy chain variable region and three were in the light chain. 28944095 11 75 theme patch 1927:1931 arg1 determinants 1947:1958 the acidic patch and undefined determinants 1916:1958 the acidic patch and undefined determinants present on the γ2 subunit constant region 1916:2000 The evidence supported that the formation of needle-like crystalline inclusions in the ER was underscored by multivalent intermolecular interactions between the acidic patch and undefined determinants present on the γ2 subunit constant region. 28944095 0 76 theme constant 99:106 arg1 region 108:113 the γ2 constant region 92:113 the γ2 constant region 92:113 Intermolecular interactions involving an acidic patch on immunoglobulin variable domain and the γ2 constant region mediate crystalline inclusion body formation in the endoplasmic reticulum. 28944095 8 77 theme aspartic 1363:1370 arg1 acids 1372:1376 eight aspartic acids 1357:1376 eight aspartic acids 1357:1376 The patch was composed of eight aspartic acids, of which five were in the heavy chain variable region and three were in the light chain. 28944095 5 78 theme transfected 1038:1048 arg1 cells 1057:1061 transfected HEK293 cells 1038:1061 transfected HEK293 cells 1038:1061 By testing various subunit combinations through mixing and matching of individual subunit chains derived from a panel of human IgG clones, we identified one secretion competent IgG2λ that induced needle-like crystalline inclusions in transfected HEK293 cells. 28944095 0 79 from patch 48:52 arg1 region 108:113 the γ2 constant region 92:113 the γ2 constant region 92:113 Intermolecular interactions involving an acidic patch on immunoglobulin variable domain and the γ2 constant region mediate crystalline inclusion body formation in the endoplasmic reticulum. 28944095 0 79 from patch 48:52 arg1 domain 81:86 immunoglobulin variable domain 57:86 immunoglobulin variable domain 57:86 Intermolecular interactions involving an acidic patch on immunoglobulin variable domain and the γ2 constant region mediate crystalline inclusion body formation in the endoplasmic reticulum. 28944095 7 80 theme negatively-charged 1274:1291 arg1 patch 1293:1297 a prominent negatively-charged patch 1262:1297 a prominent negatively-charged patch 1262:1297 Homology modeling revealed the presence of a prominent negatively-charged patch on the variable domain surface. 28944095 2 81 theme Ig 392:393 arg1 crystallization 395:409 intracellular Ig crystallization 378:409 intracellular Ig crystallization 378:409 However, numerous cases of intracellular Ig crystallization are reported in plasma cell dyscrasias. 28944095 5 82 theme individual 875:884 arg1 chains 894:899 individual subunit chains 875:899 individual subunit chains derived from a panel of human IgG clones 875:940 By testing various subunit combinations through mixing and matching of individual subunit chains derived from a panel of human IgG clones, we identified one secretion competent IgG2λ that induced needle-like crystalline inclusions in transfected HEK293 cells. 28944095 5 83 theme needle-like 1000:1010 arg1 inclusions 1024:1033 needle-like crystalline inclusions 1000:1033 needle-like crystalline inclusions in transfected HEK293 cells 1000:1061 By testing various subunit combinations through mixing and matching of individual subunit chains derived from a panel of human IgG clones, we identified one secretion competent IgG2λ that induced needle-like crystalline inclusions in transfected HEK293 cells. 28944095 11 84 theme inclusions 1828:1837 arg1 formation 1791:1799 the formation 1787:1799 the formation of needle-like crystalline inclusions in the ER 1787:1847 The evidence supported that the formation of needle-like crystalline inclusions in the ER was underscored by multivalent intermolecular interactions between the acidic patch and undefined determinants present on the γ2 subunit constant region. 28944095 8 85 theme light 1455:1459 arg1 chain 1461:1465 the light chain 1451:1465 the light chain 1451:1465 The patch was composed of eight aspartic acids, of which five were in the heavy chain variable region and three were in the light chain. 28944095 2 86 theme cell 434:437 arg1 dyscrasias 439:448 plasma cell dyscrasias 427:448 plasma cell dyscrasias 427:448 However, numerous cases of intracellular Ig crystallization are reported in plasma cell dyscrasias. 28944095 6 87 theme growth 1120:1125 arg1 conditions 1127:1136 steady-state cell growth conditions 1102:1136 steady-state cell growth conditions 1102:1136 Ig crystallization rarely occurred at steady-state cell growth conditions but was easily induced when ER-to-Golgi transport was pharmacologically blocked. 28944095 11 88 theme needle-like 1804:1814 arg1 inclusions 1828:1837 needle-like crystalline inclusions 1804:1837 needle-like crystalline inclusions 1804:1837 The evidence supported that the formation of needle-like crystalline inclusions in the ER was underscored by multivalent intermolecular interactions between the acidic patch and undefined determinants present on the γ2 subunit constant region. 28944095 0 89 theme immunoglobulin 57:70 arg1 domain 81:86 immunoglobulin variable domain 57:86 immunoglobulin variable domain 57:86 Intermolecular interactions involving an acidic patch on immunoglobulin variable domain and the γ2 constant region mediate crystalline inclusion body formation in the endoplasmic reticulum. 28944095 10 90 theme subtype 1624:1630 arg1 switching 1632:1640 subtype switching 1624:1640 subtype switching from IgG2 to IgG1 and stepwise neutralization of the acidic patch 1624:1706 Furthermore, subtype switching from IgG2 to IgG1 and stepwise neutralization of the acidic patch independently abrogated Ig crystallization events. 28944095 1 91 theme hinge 337:341 arg1 region 343:348 flexible hinge region 328:348 flexible hinge region 328:348 Full-length immunoglobulins (Igs) are widely considered difficult to crystallize because of their large size, N-linked glycosylation, and flexible hinge region. 28944095 4 92 dep searched 706:713 arg1 investigate 632:642 investigate 632:642 To investigate the underlying process of intracellular Ig crystallization 629:701 To investigate the underlying process of intracellular Ig crystallization we searched for model IgGs that can induce crystalline inclusions during recombinant overexpression. 28944095 1 93 link N-linked 300:307 arg1 glycosylation 309:321 N-linked glycosylation 300:321 N-linked glycosylation 300:321 Full-length immunoglobulins (Igs) are widely considered difficult to crystallize because of their large size, N-linked glycosylation, and flexible hinge region. 28944095 11 94 theme subunit 1978:1984 arg1 region 1995:2000 the γ2 subunit constant region 1971:2000 the γ2 subunit constant region 1971:2000 The evidence supported that the formation of needle-like crystalline inclusions in the ER was underscored by multivalent intermolecular interactions between the acidic patch and undefined determinants present on the γ2 subunit constant region. 26547982 0 0 theme Rsp5 80:83 arg1 substrates 85:94 yeast E3 ubiquitin ligase Rsp5 substrates 54:94 yeast E3 ubiquitin ligase Rsp5 substrates 54:94 In silico identification and functional annotation of yeast E3 ubiquitin ligase Rsp5 substrates. 26547982 3 1 theme in 272:273 arg1 method 282:287 an in silico method 269:287 an in silico method to recognise new substrates of Rsp5 269:323 Therefore we proposed an in silico method to recognise new substrates of Rsp5. 26547982 7 2 theme new 945:947 arg1 substrates 954:963 -66 new Rsp5 substrates 941:963 -66 new Rsp5 substrates 941:963 We also applied the model on the whole yeast proteome, and identified -66 new Rsp5 substrates. 26547982 0 3 theme ligase 73:78 arg1 substrates 85:94 yeast E3 ubiquitin ligase Rsp5 substrates 54:94 yeast E3 ubiquitin ligase Rsp5 substrates 54:94 In silico identification and functional annotation of yeast E3 ubiquitin ligase Rsp5 substrates. 26547982 5 4 theme N-linked 606:613 arg1 motif 557:561 PPxY motif 552:561 PPxY motif 552:561 It is found that PPxY motif, transmembrane region, disorder region and N-linked glycosylation modification are the most important features for substrate recognition. 26547982 5 4 theme N-linked 606:613 arg1 region 578:583 transmembrane region 564:583 transmembrane region 564:583 It is found that PPxY motif, transmembrane region, disorder region and N-linked glycosylation modification are the most important features for substrate recognition. 26547982 5 4 theme N-linked 606:613 arg1 region 595:600 disorder region 586:600 disorder region 586:600 It is found that PPxY motif, transmembrane region, disorder region and N-linked glycosylation modification are the most important features for substrate recognition. 26547982 5 4 theme N-linked 606:613 arg1 glycosylation 615:627 N-linked glycosylation 606:627 N-linked glycosylation 606:627 It is found that PPxY motif, transmembrane region, disorder region and N-linked glycosylation modification are the most important features for substrate recognition. 26547982 5 4 theme N-linked 606:613 arg1 features 665:672 the most important features 646:672 the most important features for substrate recognition 646:698 It is found that PPxY motif, transmembrane region, disorder region and N-linked glycosylation modification are the most important features for substrate recognition. 26547982 4 5 theme molecular 345:353 arg1 determinants 355:366 the molecular determinants 341:366 the molecular determinants that affect the interaction between Rsp5 and its substrate 341:425 To investigate the molecular determinants that affect the interaction between Rsp5 and its substrate, we have systematically analysed many features that perhaps correlated with the Rsp5 substrate recognition. 26547982 8 6 theme Functional 966:975 arg1 annotation 977:986 Functional annotation 966:986 Functional annotation 966:986 Functional annotation reveals that half of these novel substrates function in the Rsp5 involved cell processes as Rsp5-interacting proteins. 26547982 6 7 theme % 789:789 arg1 sensitivity 791:801 81.5% sensitivity 785:801 81.5% sensitivity 785:801 We have constructed an SVM-based classifier to recognise Rsp5 substrates, obtaining 81.5% sensitivity and 74.1% specificity averagely on ten independent testing dataset. 26547982 0 8 theme substrates 85:94 arg1 identification 10:23 In silico identification 0:23 In silico identification 0:23 In silico identification and functional annotation of yeast E3 ubiquitin ligase Rsp5 substrates. 26547982 0 8 theme substrates 85:94 arg1 annotation 40:49 functional annotation 29:49 functional annotation 29:49 In silico identification and functional annotation of yeast E3 ubiquitin ligase Rsp5 substrates. 26547982 6 9 theme 81.5 785:788 arg1 % 789:789 % 789:789 % 789:789 We have constructed an SVM-based classifier to recognise Rsp5 substrates, obtaining 81.5% sensitivity and 74.1% specificity averagely on ten independent testing dataset. 26547982 8 10 theme substrates 1021:1030 arg1 half 1001:1004 half 1001:1004 half of these novel substrates 1001:1030 Functional annotation reveals that half of these novel substrates function in the Rsp5 involved cell processes as Rsp5-interacting proteins. 26547982 8 10 theme substrates 1021:1030 arg1 proteins 1097:1104 Rsp5-interacting proteins 1080:1104 Rsp5-interacting proteins 1080:1104 Functional annotation reveals that half of these novel substrates function in the Rsp5 involved cell processes as Rsp5-interacting proteins. 26547982 5 11 theme transmembrane 564:576 arg1 motif 557:561 PPxY motif 552:561 PPxY motif 552:561 It is found that PPxY motif, transmembrane region, disorder region and N-linked glycosylation modification are the most important features for substrate recognition. 26547982 5 11 theme transmembrane 564:576 arg1 region 578:583 transmembrane region 564:583 transmembrane region 564:583 It is found that PPxY motif, transmembrane region, disorder region and N-linked glycosylation modification are the most important features for substrate recognition. 26547982 5 11 theme transmembrane 564:576 arg1 region 595:600 disorder region 586:600 disorder region 586:600 It is found that PPxY motif, transmembrane region, disorder region and N-linked glycosylation modification are the most important features for substrate recognition. 26547982 5 11 theme transmembrane 564:576 arg1 glycosylation 615:627 N-linked glycosylation 606:627 N-linked glycosylation 606:627 It is found that PPxY motif, transmembrane region, disorder region and N-linked glycosylation modification are the most important features for substrate recognition. 26547982 5 11 theme transmembrane 564:576 arg1 features 665:672 the most important features 646:672 the most important features for substrate recognition 646:698 It is found that PPxY motif, transmembrane region, disorder region and N-linked glycosylation modification are the most important features for substrate recognition. 26547982 3 12 theme new 302:304 arg1 substrates 306:315 new substrates 302:315 new substrates of Rsp5 302:323 Therefore we proposed an in silico method to recognise new substrates of Rsp5. 26547982 8 13 theme novel 1015:1019 arg1 substrates 1021:1030 these novel substrates 1009:1030 these novel substrates 1009:1030 Functional annotation reveals that half of these novel substrates function in the Rsp5 involved cell processes as Rsp5-interacting proteins. 26547982 7 14 theme whole 904:908 arg1 proteome 916:923 the whole yeast proteome 900:923 the whole yeast proteome 900:923 We also applied the model on the whole yeast proteome, and identified -66 new Rsp5 substrates. 26547982 6 15 theme testing 854:860 arg1 dataset 862:868 ten independent testing dataset 838:868 ten independent testing dataset 838:868 We have constructed an SVM-based classifier to recognise Rsp5 substrates, obtaining 81.5% sensitivity and 74.1% specificity averagely on ten independent testing dataset. 26547982 5 16 theme disorder 586:593 arg1 motif 557:561 PPxY motif 552:561 PPxY motif 552:561 It is found that PPxY motif, transmembrane region, disorder region and N-linked glycosylation modification are the most important features for substrate recognition. 26547982 5 16 theme disorder 586:593 arg1 region 578:583 transmembrane region 564:583 transmembrane region 564:583 It is found that PPxY motif, transmembrane region, disorder region and N-linked glycosylation modification are the most important features for substrate recognition. 26547982 5 16 theme disorder 586:593 arg1 region 595:600 disorder region 586:600 disorder region 586:600 It is found that PPxY motif, transmembrane region, disorder region and N-linked glycosylation modification are the most important features for substrate recognition. 26547982 5 16 theme disorder 586:593 arg1 glycosylation 615:627 N-linked glycosylation 606:627 N-linked glycosylation 606:627 It is found that PPxY motif, transmembrane region, disorder region and N-linked glycosylation modification are the most important features for substrate recognition. 26547982 5 16 theme disorder 586:593 arg1 features 665:672 the most important features 646:672 the most important features for substrate recognition 646:698 It is found that PPxY motif, transmembrane region, disorder region and N-linked glycosylation modification are the most important features for substrate recognition. 26547982 7 17 theme yeast 910:914 arg1 proteome 916:923 the whole yeast proteome 900:923 the whole yeast proteome 900:923 We also applied the model on the whole yeast proteome, and identified -66 new Rsp5 substrates. 26547982 1 18 theme key 155:157 arg1 role 159:162 a key role 153:162 a key role 153:162 Rsp5, E3 ligases conserved from yeast to mammals, plays a key role in diverse processes in yeast. 26547982 0 19 theme In 0:1 arg1 identification 10:23 In silico identification 0:23 In silico identification 0:23 In silico identification and functional annotation of yeast E3 ubiquitin ligase Rsp5 substrates. 26547982 4 20 theme substrate 512:520 arg1 recognition 522:532 the Rsp5 substrate recognition 503:532 the Rsp5 substrate recognition 503:532 To investigate the molecular determinants that affect the interaction between Rsp5 and its substrate, we have systematically analysed many features that perhaps correlated with the Rsp5 substrate recognition. 26547982 6 21 theme Rsp5 758:761 arg1 substrates 763:772 Rsp5 substrates 758:772 Rsp5 substrates 758:772 We have constructed an SVM-based classifier to recognise Rsp5 substrates, obtaining 81.5% sensitivity and 74.1% specificity averagely on ten independent testing dataset. 26547982 3 22 theme Rsp5 320:323 arg1 substrates 306:315 new substrates 302:315 new substrates of Rsp5 302:323 Therefore we proposed an in silico method to recognise new substrates of Rsp5. 26547982 4 23 theme Rsp5 507:510 arg1 recognition 522:532 the Rsp5 substrate recognition 503:532 the Rsp5 substrate recognition 503:532 To investigate the molecular determinants that affect the interaction between Rsp5 and its substrate, we have systematically analysed many features that perhaps correlated with the Rsp5 substrate recognition. 26547982 3 24 dep in 272:273 arg1 silico 275:280 silico 275:280 silico 275:280 Therefore we proposed an in silico method to recognise new substrates of Rsp5. 26547982 5 25 theme PPxY 552:555 arg1 motif 557:561 PPxY motif 552:561 PPxY motif 552:561 It is found that PPxY motif, transmembrane region, disorder region and N-linked glycosylation modification are the most important features for substrate recognition. 26547982 5 25 theme PPxY 552:555 arg1 region 578:583 transmembrane region 564:583 transmembrane region 564:583 It is found that PPxY motif, transmembrane region, disorder region and N-linked glycosylation modification are the most important features for substrate recognition. 26547982 5 25 theme PPxY 552:555 arg1 region 595:600 disorder region 586:600 disorder region 586:600 It is found that PPxY motif, transmembrane region, disorder region and N-linked glycosylation modification are the most important features for substrate recognition. 26547982 5 25 theme PPxY 552:555 arg1 glycosylation 615:627 N-linked glycosylation 606:627 N-linked glycosylation 606:627 It is found that PPxY motif, transmembrane region, disorder region and N-linked glycosylation modification are the most important features for substrate recognition. 26547982 5 25 theme PPxY 552:555 arg1 features 665:672 the most important features 646:672 the most important features for substrate recognition 646:698 It is found that PPxY motif, transmembrane region, disorder region and N-linked glycosylation modification are the most important features for substrate recognition. 26547982 6 26 theme independent 842:852 arg1 dataset 862:868 ten independent testing dataset 838:868 ten independent testing dataset 838:868 We have constructed an SVM-based classifier to recognise Rsp5 substrates, obtaining 81.5% sensitivity and 74.1% specificity averagely on ten independent testing dataset. 26547982 7 27 from model 891:895 arg1 proteome 916:923 the whole yeast proteome 900:923 the whole yeast proteome 900:923 We also applied the model on the whole yeast proteome, and identified -66 new Rsp5 substrates. 26547982 1 28 theme diverse 167:173 arg1 processes 175:183 diverse processes 167:183 diverse processes in yeast 167:192 Rsp5, E3 ligases conserved from yeast to mammals, plays a key role in diverse processes in yeast. 26547982 5 29 theme substrate 678:686 arg1 recognition 688:698 substrate recognition 678:698 substrate recognition 678:698 It is found that PPxY motif, transmembrane region, disorder region and N-linked glycosylation modification are the most important features for substrate recognition. 26547982 0 30 theme functional 29:38 arg1 annotation 40:49 functional annotation 29:49 functional annotation 29:49 In silico identification and functional annotation of yeast E3 ubiquitin ligase Rsp5 substrates. 26547982 8 31 theme involved 1053:1060 arg1 processes 1067:1075 the Rsp5 involved cell processes 1044:1075 the Rsp5 involved cell processes 1044:1075 Functional annotation reveals that half of these novel substrates function in the Rsp5 involved cell processes as Rsp5-interacting proteins. 26547982 1 32 from processes 175:183 arg1 yeast 188:192 yeast 188:192 yeast 188:192 Rsp5, E3 ligases conserved from yeast to mammals, plays a key role in diverse processes in yeast. 26547982 5 33 link N-linked 606:613 arg1 motif 557:561 PPxY motif 552:561 PPxY motif 552:561 It is found that PPxY motif, transmembrane region, disorder region and N-linked glycosylation modification are the most important features for substrate recognition. 26547982 5 33 link N-linked 606:613 arg1 region 578:583 transmembrane region 564:583 transmembrane region 564:583 It is found that PPxY motif, transmembrane region, disorder region and N-linked glycosylation modification are the most important features for substrate recognition. 26547982 5 33 link N-linked 606:613 arg1 region 595:600 disorder region 586:600 disorder region 586:600 It is found that PPxY motif, transmembrane region, disorder region and N-linked glycosylation modification are the most important features for substrate recognition. 26547982 5 33 link N-linked 606:613 arg1 glycosylation 615:627 N-linked glycosylation 606:627 N-linked glycosylation 606:627 It is found that PPxY motif, transmembrane region, disorder region and N-linked glycosylation modification are the most important features for substrate recognition. 26547982 5 33 link N-linked 606:613 arg1 features 665:672 the most important features 646:672 the most important features for substrate recognition 646:698 It is found that PPxY motif, transmembrane region, disorder region and N-linked glycosylation modification are the most important features for substrate recognition. 26547982 0 34 theme yeast 54:58 arg1 ligase 73:78 yeast E3 ubiquitin ligase 54:78 yeast E3 ubiquitin ligase Rsp5 substrates 54:94 In silico identification and functional annotation of yeast E3 ubiquitin ligase Rsp5 substrates. 26547982 1 35 theme E3 103:104 arg1 Rsp5 97:100 Rsp5 97:100 Rsp5 97:100 Rsp5, E3 ligases conserved from yeast to mammals, plays a key role in diverse processes in yeast. 26547982 1 35 theme E3 103:104 arg1 ligases 106:112 E3 ligases 103:112 E3 ligases conserved from yeast to mammals 103:144 Rsp5, E3 ligases conserved from yeast to mammals, plays a key role in diverse processes in yeast. 26547982 8 36 theme Rsp5 1048:1051 arg1 processes 1067:1075 the Rsp5 involved cell processes 1044:1075 the Rsp5 involved cell processes 1044:1075 Functional annotation reveals that half of these novel substrates function in the Rsp5 involved cell processes as Rsp5-interacting proteins. 26547982 6 37 theme SVM-based 724:732 arg1 classifier 734:743 an SVM-based classifier 721:743 an SVM-based classifier 721:743 We have constructed an SVM-based classifier to recognise Rsp5 substrates, obtaining 81.5% sensitivity and 74.1% specificity averagely on ten independent testing dataset. 26547982 8 38 theme cell 1062:1065 arg1 processes 1067:1075 the Rsp5 involved cell processes 1044:1075 the Rsp5 involved cell processes 1044:1075 Functional annotation reveals that half of these novel substrates function in the Rsp5 involved cell processes as Rsp5-interacting proteins. 26547982 6 39 theme % 811:811 arg1 specificity 813:823 74.1% specificity 807:823 74.1% specificity 807:823 We have constructed an SVM-based classifier to recognise Rsp5 substrates, obtaining 81.5% sensitivity and 74.1% specificity averagely on ten independent testing dataset. 26547982 2 40 theme substrates 217:226 arg1 many 204:207 many 204:207 many 204:207 However, many of Rsp5 substrates are still unclear. 26547982 2 40 theme substrates 217:226 arg1 substrates 217:226 Rsp5 substrates 212:226 Rsp5 substrates 212:226 However, many of Rsp5 substrates are still unclear. 26547982 8 41 theme Rsp5-interacting 1080:1095 arg1 half 1001:1004 half 1001:1004 half of these novel substrates 1001:1030 Functional annotation reveals that half of these novel substrates function in the Rsp5 involved cell processes as Rsp5-interacting proteins. 26547982 8 41 theme Rsp5-interacting 1080:1095 arg1 proteins 1097:1104 Rsp5-interacting proteins 1080:1104 Rsp5-interacting proteins 1080:1104 Functional annotation reveals that half of these novel substrates function in the Rsp5 involved cell processes as Rsp5-interacting proteins. 26547982 5 42 theme important 655:663 arg1 motif 557:561 PPxY motif 552:561 PPxY motif 552:561 It is found that PPxY motif, transmembrane region, disorder region and N-linked glycosylation modification are the most important features for substrate recognition. 26547982 5 42 theme important 655:663 arg1 region 578:583 transmembrane region 564:583 transmembrane region 564:583 It is found that PPxY motif, transmembrane region, disorder region and N-linked glycosylation modification are the most important features for substrate recognition. 26547982 5 42 theme important 655:663 arg1 region 595:600 disorder region 586:600 disorder region 586:600 It is found that PPxY motif, transmembrane region, disorder region and N-linked glycosylation modification are the most important features for substrate recognition. 26547982 5 42 theme important 655:663 arg1 glycosylation 615:627 N-linked glycosylation 606:627 N-linked glycosylation 606:627 It is found that PPxY motif, transmembrane region, disorder region and N-linked glycosylation modification are the most important features for substrate recognition. 26547982 5 42 theme important 655:663 arg1 features 665:672 the most important features 646:672 the most important features for substrate recognition 646:698 It is found that PPxY motif, transmembrane region, disorder region and N-linked glycosylation modification are the most important features for substrate recognition. 26547982 6 43 theme 74.1 807:810 arg1 % 811:811 % 811:811 % 811:811 We have constructed an SVM-based classifier to recognise Rsp5 substrates, obtaining 81.5% sensitivity and 74.1% specificity averagely on ten independent testing dataset. 26547982 2 44 theme Rsp5 212:215 arg1 substrates 217:226 Rsp5 substrates 212:226 Rsp5 substrates 212:226 However, many of Rsp5 substrates are still unclear. 26547982 7 45 theme Rsp5 949:952 arg1 substrates 954:963 -66 new Rsp5 substrates 941:963 -66 new Rsp5 substrates 941:963 We also applied the model on the whole yeast proteome, and identified -66 new Rsp5 substrates. 26547982 0 46 theme ubiquitin 63:71 arg1 ligase 73:78 yeast E3 ubiquitin ligase 54:78 yeast E3 ubiquitin ligase Rsp5 substrates 54:94 In silico identification and functional annotation of yeast E3 ubiquitin ligase Rsp5 substrates. 26547982 5 47 dep motif 557:561 arg1 modification 629:640 modification 629:640 modification 629:640 It is found that PPxY motif, transmembrane region, disorder region and N-linked glycosylation modification are the most important features for substrate recognition. 26547982 0 48 theme E3 60:61 arg1 ligase 73:78 yeast E3 ubiquitin ligase 54:78 yeast E3 ubiquitin ligase Rsp5 substrates 54:94 In silico identification and functional annotation of yeast E3 ubiquitin ligase Rsp5 substrates. 26547982 4 49 theme many 460:463 arg1 features 465:472 many features 460:472 many features that perhaps correlated with the Rsp5 substrate recognition 460:532 To investigate the molecular determinants that affect the interaction between Rsp5 and its substrate, we have systematically analysed many features that perhaps correlated with the Rsp5 substrate recognition. 26547982 0 50 dep In 0:1 arg1 silico 3:8 silico 3:8 silico 3:8 In silico identification and functional annotation of yeast E3 ubiquitin ligase Rsp5 substrates. 25199249 8 0 theme delta 1192:1196 arg1 strain 1203:1208 delta och1 delta alg3 delta mnn1 strain 1170:1208 delta och1 delta alg3 delta mnn1 strain 1170:1208 Our approach for adaptive evolution resulted a remarkable improvement on the growth phenotype of delta och1 delta alg3 delta mnn1 strain. 25199249 10 1 theme single 1435:1440 arg1 form 1454:1457 form 1454:1457 form 1454:1457 Treatment with alpha-1,2-mannosidase converted both Man,GlcNAc2 and Man,GlcNAc2 products to a single Man3GlcNAc, form, indicating that the additional mannose on Man,GlcNAc, product comes from an alpha-1, 2 modification. 25199249 10 1 theme single 1435:1440 arg1 Man3GlcNAc 1442:1451 a single Man3GlcNAc 1433:1451 a single Man3GlcNAc 1433:1451 Treatment with alpha-1,2-mannosidase converted both Man,GlcNAc2 and Man,GlcNAc2 products to a single Man3GlcNAc, form, indicating that the additional mannose on Man,GlcNAc, product comes from an alpha-1, 2 modification. 25199249 8 2 theme strain 1203:1208 arg1 phenotype 1157:1165 the growth phenotype 1146:1165 the growth phenotype of delta och1 delta alg3 delta mnn1 strain 1146:1208 Our approach for adaptive evolution resulted a remarkable improvement on the growth phenotype of delta och1 delta alg3 delta mnn1 strain. 25199249 5 3 theme invertase 702:710 arg1 staining 690:697 the activity staining 677:697 the activity staining of invertase 677:710 The N-linked oligosaccharides from the mutant cells were analyzed by the activity staining of invertase, and their structure was further confirmed by high-performance liquid chromatography (HPLC) and the treatment with glycosidase. 25199249 5 4 with treatment 812:820 arg1 glycosidase 827:837 glycosidase 827:837 glycosidase 827:837 The N-linked oligosaccharides from the mutant cells were analyzed by the activity staining of invertase, and their structure was further confirmed by high-performance liquid chromatography (HPLC) and the treatment with glycosidase. 25199249 2 5 theme yeast 409:413 arg1 pathway 431:437 yeast N-glycosylation pathway 409:437 yeast N-glycosylation pathway 409:437 We tried to construct a strain, which can be used to introduce human N-glycosylation reactions, by disrupting several special glycosyltransferases in yeast N-glycosylation pathway. 25199249 9 6 theme small 1244:1248 arg1 intermediate 1283:1294 unexpected Man6GlcNAc2 intermediate 1260:1294 unexpected Man6GlcNAc2 intermediate from delta och1delta alg3 delta mnnl strain 1260:1338 In addition, we also confirmed a small amount of unexpected Man6GlcNAc2 intermediate from delta och1delta alg3 delta mnnl strain. 25199249 9 6 theme small 1244:1248 arg1 amount 1250:1255 a small amount 1242:1255 a small amount of unexpected Man6GlcNAc2 intermediate from delta och1delta alg3 delta mnnl strain 1242:1338 In addition, we also confirmed a small amount of unexpected Man6GlcNAc2 intermediate from delta och1delta alg3 delta mnnl strain. 25199249 9 7 from strain 1333:1338 arg1 intermediate 1283:1294 unexpected Man6GlcNAc2 intermediate 1260:1294 unexpected Man6GlcNAc2 intermediate from delta och1delta alg3 delta mnnl strain 1260:1338 In addition, we also confirmed a small amount of unexpected Man6GlcNAc2 intermediate from delta och1delta alg3 delta mnnl strain. 25199249 9 7 from strain 1333:1338 arg1 amount 1250:1255 a small amount 1242:1255 a small amount of unexpected Man6GlcNAc2 intermediate from delta och1delta alg3 delta mnnl strain 1242:1338 In addition, we also confirmed a small amount of unexpected Man6GlcNAc2 intermediate from delta och1delta alg3 delta mnnl strain. 25199249 5 8 with chromatography 782:795 arg1 glycosidase 827:837 glycosidase 827:837 glycosidase 827:837 The N-linked oligosaccharides from the mutant cells were analyzed by the activity staining of invertase, and their structure was further confirmed by high-performance liquid chromatography (HPLC) and the treatment with glycosidase. 25199249 9 9 theme Man6GlcNAc2 1271:1281 arg1 intermediate 1283:1294 unexpected Man6GlcNAc2 intermediate 1260:1294 unexpected Man6GlcNAc2 intermediate from delta och1delta alg3 delta mnnl strain 1260:1338 In addition, we also confirmed a small amount of unexpected Man6GlcNAc2 intermediate from delta och1delta alg3 delta mnnl strain. 25199249 7 10 theme human 1050:1054 arg1 N-glycosylation 1056:1070 human N-glycosylation 1050:1070 human N-glycosylation 1050:1070 RESULTS & CONCLUSION We obtained a delta och1 delta alg3 delta mnn1 strain that produces Man5 GlcNAc2 intermediate of human N-glycosylation. 25199249 1 11 theme yeast 247:251 arg1 cell 253:256 the yeast cell 243:256 the yeast cell 243:256 OBJECTIVE To produce human glycoproteins in Saccharomyces cerevisiae, human N-glycosylation pathway must be genetically engineered into the yeast cell. 25199249 10 12 from mannose 1491:1497 arg1 product 1514:1520 product 1514:1520 product 1514:1520 Treatment with alpha-1,2-mannosidase converted both Man,GlcNAc2 and Man,GlcNAc2 products to a single Man3GlcNAc, form, indicating that the additional mannose on Man,GlcNAc, product comes from an alpha-1, 2 modification. 25199249 10 12 from mannose 1491:1497 arg1 GlcNAc 1506:1511 GlcNAc 1506:1511 GlcNAc 1506:1511 Treatment with alpha-1,2-mannosidase converted both Man,GlcNAc2 and Man,GlcNAc2 products to a single Man3GlcNAc, form, indicating that the additional mannose on Man,GlcNAc, product comes from an alpha-1, 2 modification. 25199249 10 12 from mannose 1491:1497 arg1 Man 1502:1504 Man 1502:1504 Man 1502:1504 Treatment with alpha-1,2-mannosidase converted both Man,GlcNAc2 and Man,GlcNAc2 products to a single Man3GlcNAc, form, indicating that the additional mannose on Man,GlcNAc, product comes from an alpha-1, 2 modification. 25199249 7 13 theme delta 967:971 arg1 strain 1000:1005 a delta och1 delta alg3 delta mnn1 strain 965:1005 a delta och1 delta alg3 delta mnn1 strain that produces Man5 GlcNAc2 intermediate of human N-glycosylation 965:1070 RESULTS & CONCLUSION We obtained a delta och1 delta alg3 delta mnn1 strain that produces Man5 GlcNAc2 intermediate of human N-glycosylation. 25199249 5 14 link N-linked 612:619 arg1 oligosaccharides 621:636 The N-linked oligosaccharides 608:636 The N-linked oligosaccharides from the mutant cells 608:658 The N-linked oligosaccharides from the mutant cells were analyzed by the activity staining of invertase, and their structure was further confirmed by high-performance liquid chromatography (HPLC) and the treatment with glycosidase. 25199249 9 15 theme och1delta 1307:1315 arg1 strain 1333:1338 delta och1delta alg3 delta mnnl strain 1301:1338 delta och1delta alg3 delta mnnl strain 1301:1338 In addition, we also confirmed a small amount of unexpected Man6GlcNAc2 intermediate from delta och1delta alg3 delta mnnl strain. 25199249 7 16 theme Man5 1021:1024 arg1 intermediate 1034:1045 Man5 GlcNAc2 intermediate 1021:1045 Man5 GlcNAc2 intermediate of human N-glycosylation 1021:1070 RESULTS & CONCLUSION We obtained a delta och1 delta alg3 delta mnn1 strain that produces Man5 GlcNAc2 intermediate of human N-glycosylation. 25199249 9 17 theme delta 1322:1326 arg1 strain 1333:1338 delta och1delta alg3 delta mnnl strain 1301:1338 delta och1delta alg3 delta mnnl strain 1301:1338 In addition, we also confirmed a small amount of unexpected Man6GlcNAc2 intermediate from delta och1delta alg3 delta mnnl strain. 25199249 5 18 from cells 654:658 arg1 oligosaccharides 621:636 The N-linked oligosaccharides 608:636 The N-linked oligosaccharides from the mutant cells 608:658 The N-linked oligosaccharides from the mutant cells were analyzed by the activity staining of invertase, and their structure was further confirmed by high-performance liquid chromatography (HPLC) and the treatment with glycosidase. 25199249 10 19 theme additional 1480:1489 arg1 mannose 1491:1497 the additional mannose 1476:1497 the additional mannose on Man,GlcNAc, product 1476:1520 Treatment with alpha-1,2-mannosidase converted both Man,GlcNAc2 and Man,GlcNAc2 products to a single Man3GlcNAc, form, indicating that the additional mannose on Man,GlcNAc, product comes from an alpha-1, 2 modification. 25199249 7 20 theme mnn1 995:998 arg1 strain 1000:1005 a delta och1 delta alg3 delta mnn1 strain 965:1005 a delta och1 delta alg3 delta mnn1 strain that produces Man5 GlcNAc2 intermediate of human N-glycosylation 965:1070 RESULTS & CONCLUSION We obtained a delta och1 delta alg3 delta mnn1 strain that produces Man5 GlcNAc2 intermediate of human N-glycosylation. 25199249 1 21 theme N-glycosylation 183:197 arg1 pathway 199:205 human N-glycosylation pathway 177:205 human N-glycosylation pathway 177:205 OBJECTIVE To produce human glycoproteins in Saccharomyces cerevisiae, human N-glycosylation pathway must be genetically engineered into the yeast cell. 25199249 11 22 theme human 1786:1790 arg1 pathway 1808:1814 human N-glycosylation pathway 1786:1814 human N-glycosylation pathway 1786:1814 Our results demonstrate that delta och1 delta alg3 deltamnn1 triple mutant can be used as an initial strain to construct an yeast therapeutic glycoprotein-expression system by introducing various enzymes that are involved in human N-glycosylation pathway. 25199249 5 23 theme liquid 775:780 arg1 chromatography 782:795 high-performance liquid chromatography 758:795 high-performance liquid chromatography (HPLC) 758:802 The N-linked oligosaccharides from the mutant cells were analyzed by the activity staining of invertase, and their structure was further confirmed by high-performance liquid chromatography (HPLC) and the treatment with glycosidase. 25199249 5 23 theme liquid 775:780 arg1 HPLC 798:801 HPLC 798:801 HPLC 798:801 The N-linked oligosaccharides from the mutant cells were analyzed by the activity staining of invertase, and their structure was further confirmed by high-performance liquid chromatography (HPLC) and the treatment with glycosidase. 25199249 7 24 theme alg3 984:987 arg1 strain 1000:1005 a delta och1 delta alg3 delta mnn1 strain 965:1005 a delta och1 delta alg3 delta mnn1 strain that produces Man5 GlcNAc2 intermediate of human N-glycosylation 965:1070 RESULTS & CONCLUSION We obtained a delta och1 delta alg3 delta mnn1 strain that produces Man5 GlcNAc2 intermediate of human N-glycosylation. 25199249 8 25 theme adaptive 1090:1097 arg1 evolution 1099:1107 adaptive evolution 1090:1107 adaptive evolution 1090:1107 Our approach for adaptive evolution resulted a remarkable improvement on the growth phenotype of delta och1 delta alg3 delta mnn1 strain. 25199249 7 26 theme och1 973:976 arg1 strain 1000:1005 a delta och1 delta alg3 delta mnn1 strain 965:1005 a delta och1 delta alg3 delta mnn1 strain that produces Man5 GlcNAc2 intermediate of human N-glycosylation 965:1070 RESULTS & CONCLUSION We obtained a delta och1 delta alg3 delta mnn1 strain that produces Man5 GlcNAc2 intermediate of human N-glycosylation. 25199249 3 27 theme mutant 458:463 arg1 cell 465:468 this mutant cell 453:468 this mutant cell 453:468 Furthermore, this mutant cell was applied for adaptive evolution to overcome its growth-defect phenotype. 25199249 5 28 theme N-linked 612:619 arg1 oligosaccharides 621:636 The N-linked oligosaccharides 608:636 The N-linked oligosaccharides from the mutant cells 608:658 The N-linked oligosaccharides from the mutant cells were analyzed by the activity staining of invertase, and their structure was further confirmed by high-performance liquid chromatography (HPLC) and the treatment with glycosidase. 25199249 7 29 dep obtained 956:963 arg1 & 940:940 & 940:940 & CONCLUSION 940:951 RESULTS & CONCLUSION We obtained a delta och1 delta alg3 delta mnn1 strain that produces Man5 GlcNAc2 intermediate of human N-glycosylation. 25199249 0 30 theme N-glycosylation 19:33 arg1 pathway 35:41 N-glycosylation pathway 19:41 N-glycosylation pathway 19:41 [Reconstruction of N-glycosylation pathway for producing human glycoproteins in Saccharomyces cerevisiae]. 25199249 8 31 theme remarkable 1120:1129 arg1 improvement 1131:1141 a remarkable improvement 1118:1141 a remarkable improvement on the growth phenotype of delta och1 delta alg3 delta mnn1 strain 1118:1208 Our approach for adaptive evolution resulted a remarkable improvement on the growth phenotype of delta och1 delta alg3 delta mnn1 strain. 25199249 11 32 theme therapeutic 1691:1701 arg1 system 1727:1732 an yeast therapeutic glycoprotein-expression system 1682:1732 an yeast therapeutic glycoprotein-expression system 1682:1732 Our results demonstrate that delta och1 delta alg3 deltamnn1 triple mutant can be used as an initial strain to construct an yeast therapeutic glycoprotein-expression system by introducing various enzymes that are involved in human N-glycosylation pathway. 25199249 11 33 theme deltamnn1 1612:1620 arg1 mutant 1629:1634 delta och1 delta alg3 deltamnn1 triple mutant 1590:1634 delta och1 delta alg3 deltamnn1 triple mutant 1590:1634 Our results demonstrate that delta och1 delta alg3 deltamnn1 triple mutant can be used as an initial strain to construct an yeast therapeutic glycoprotein-expression system by introducing various enzymes that are involved in human N-glycosylation pathway. 25199249 11 33 theme deltamnn1 1612:1620 arg1 strain 1662:1667 an initial strain 1651:1667 an initial strain 1651:1667 Our results demonstrate that delta och1 delta alg3 deltamnn1 triple mutant can be used as an initial strain to construct an yeast therapeutic glycoprotein-expression system by introducing various enzymes that are involved in human N-glycosylation pathway. 25199249 3 34 theme growth-defect 521:533 arg1 phenotype 535:543 its growth-defect phenotype 517:543 its growth-defect phenotype 517:543 Furthermore, this mutant cell was applied for adaptive evolution to overcome its growth-defect phenotype. 25199249 0 35 theme human 57:61 arg1 glycoproteins 63:75 human glycoproteins 57:75 human glycoproteins in Saccharomyces cerevisiae 57:103 [Reconstruction of N-glycosylation pathway for producing human glycoproteins in Saccharomyces cerevisiae]. 25199249 8 36 theme growth 1150:1155 arg1 phenotype 1157:1165 the growth phenotype 1146:1165 the growth phenotype of delta och1 delta alg3 delta mnn1 strain 1146:1208 Our approach for adaptive evolution resulted a remarkable improvement on the growth phenotype of delta och1 delta alg3 delta mnn1 strain. 25199249 2 37 used used 304:307 arg2 strain 283:288 a strain 281:288 a strain 281:288 We tried to construct a strain, which can be used to introduce human N-glycosylation reactions, by disrupting several special glycosyltransferases in yeast N-glycosylation pathway. 25199249 11 38 theme delta 1601:1605 arg1 mutant 1629:1634 delta och1 delta alg3 deltamnn1 triple mutant 1590:1634 delta och1 delta alg3 deltamnn1 triple mutant 1590:1634 Our results demonstrate that delta och1 delta alg3 deltamnn1 triple mutant can be used as an initial strain to construct an yeast therapeutic glycoprotein-expression system by introducing various enzymes that are involved in human N-glycosylation pathway. 25199249 11 38 theme delta 1601:1605 arg1 strain 1662:1667 an initial strain 1651:1667 an initial strain 1651:1667 Our results demonstrate that delta och1 delta alg3 deltamnn1 triple mutant can be used as an initial strain to construct an yeast therapeutic glycoprotein-expression system by introducing various enzymes that are involved in human N-glycosylation pathway. 25199249 8 39 theme och1 1176:1179 arg1 strain 1203:1208 delta och1 delta alg3 delta mnn1 strain 1170:1208 delta och1 delta alg3 delta mnn1 strain 1170:1208 Our approach for adaptive evolution resulted a remarkable improvement on the growth phenotype of delta och1 delta alg3 delta mnn1 strain. 25199249 0 40 gly glycoproteins 63:75 arg1 glycoproteins 63:75 human glycoproteins 57:75 human glycoproteins in Saccharomyces cerevisiae 57:103 [Reconstruction of N-glycosylation pathway for producing human glycoproteins in Saccharomyces cerevisiae]. 25199249 11 41 theme initial 1654:1660 arg1 mutant 1629:1634 delta och1 delta alg3 deltamnn1 triple mutant 1590:1634 delta och1 delta alg3 deltamnn1 triple mutant 1590:1634 Our results demonstrate that delta och1 delta alg3 deltamnn1 triple mutant can be used as an initial strain to construct an yeast therapeutic glycoprotein-expression system by introducing various enzymes that are involved in human N-glycosylation pathway. 25199249 11 41 theme initial 1654:1660 arg1 strain 1662:1667 an initial strain 1651:1667 an initial strain 1651:1667 Our results demonstrate that delta och1 delta alg3 deltamnn1 triple mutant can be used as an initial strain to construct an yeast therapeutic glycoprotein-expression system by introducing various enzymes that are involved in human N-glycosylation pathway. 25199249 5 42 theme activity 681:688 arg1 staining 690:697 the activity staining 677:697 the activity staining of invertase 677:710 The N-linked oligosaccharides from the mutant cells were analyzed by the activity staining of invertase, and their structure was further confirmed by high-performance liquid chromatography (HPLC) and the treatment with glycosidase. 25199249 2 43 theme several 369:375 arg1 glycosyltransferases 385:404 several special glycosyltransferases 369:404 several special glycosyltransferases 369:404 We tried to construct a strain, which can be used to introduce human N-glycosylation reactions, by disrupting several special glycosyltransferases in yeast N-glycosylation pathway. 25199249 8 44 theme alg3 1187:1190 arg1 strain 1203:1208 delta och1 delta alg3 delta mnn1 strain 1170:1208 delta och1 delta alg3 delta mnn1 strain 1170:1208 Our approach for adaptive evolution resulted a remarkable improvement on the growth phenotype of delta och1 delta alg3 delta mnn1 strain. 25199249 8 45 theme mnn1 1198:1201 arg1 strain 1203:1208 delta och1 delta alg3 delta mnn1 strain 1170:1208 delta och1 delta alg3 delta mnn1 strain 1170:1208 Our approach for adaptive evolution resulted a remarkable improvement on the growth phenotype of delta och1 delta alg3 delta mnn1 strain. 25199249 6 46 theme Mutant 840:845 arg1 cells 847:851 Mutant cells 840:851 Mutant cells 840:851 Mutant cells were cultured under a high temperature for their adaptive evolution of growth. 25199249 6 47 theme growth 924:929 arg1 evolution 911:919 their adaptive evolution 896:919 their adaptive evolution of growth 896:929 Mutant cells were cultured under a high temperature for their adaptive evolution of growth. 25199249 11 48 theme delta 1590:1594 arg1 mutant 1629:1634 delta och1 delta alg3 deltamnn1 triple mutant 1590:1634 delta och1 delta alg3 deltamnn1 triple mutant 1590:1634 Our results demonstrate that delta och1 delta alg3 deltamnn1 triple mutant can be used as an initial strain to construct an yeast therapeutic glycoprotein-expression system by introducing various enzymes that are involved in human N-glycosylation pathway. 25199249 11 48 theme delta 1590:1594 arg1 strain 1662:1667 an initial strain 1651:1667 an initial strain 1651:1667 Our results demonstrate that delta och1 delta alg3 deltamnn1 triple mutant can be used as an initial strain to construct an yeast therapeutic glycoprotein-expression system by introducing various enzymes that are involved in human N-glycosylation pathway. 25199249 2 49 theme human 322:326 arg1 reactions 344:352 human N-glycosylation reactions 322:352 human N-glycosylation reactions 322:352 We tried to construct a strain, which can be used to introduce human N-glycosylation reactions, by disrupting several special glycosyltransferases in yeast N-glycosylation pathway. 25199249 11 50 used used 1643:1646 arg2 mutant 1629:1634 delta och1 delta alg3 deltamnn1 triple mutant 1590:1634 delta och1 delta alg3 deltamnn1 triple mutant 1590:1634 Our results demonstrate that delta och1 delta alg3 deltamnn1 triple mutant can be used as an initial strain to construct an yeast therapeutic glycoprotein-expression system by introducing various enzymes that are involved in human N-glycosylation pathway. 25199249 11 50 used used 1643:1646 arg2 strain 1662:1667 an initial strain 1651:1667 an initial strain 1651:1667 Our results demonstrate that delta och1 delta alg3 deltamnn1 triple mutant can be used as an initial strain to construct an yeast therapeutic glycoprotein-expression system by introducing various enzymes that are involved in human N-glycosylation pathway. 25199249 1 51 gly glycoproteins 134:146 arg1 glycoproteins 134:146 human glycoproteins 128:146 human glycoproteins in Saccharomyces cerevisiae 128:174 OBJECTIVE To produce human glycoproteins in Saccharomyces cerevisiae, human N-glycosylation pathway must be genetically engineered into the yeast cell. 25199249 9 52 theme unexpected 1260:1269 arg1 intermediate 1283:1294 unexpected Man6GlcNAc2 intermediate 1260:1294 unexpected Man6GlcNAc2 intermediate from delta och1delta alg3 delta mnnl strain 1260:1338 In addition, we also confirmed a small amount of unexpected Man6GlcNAc2 intermediate from delta och1delta alg3 delta mnnl strain. 25199249 9 53 theme intermediate 1283:1294 arg1 intermediate 1283:1294 unexpected Man6GlcNAc2 intermediate 1260:1294 unexpected Man6GlcNAc2 intermediate from delta och1delta alg3 delta mnnl strain 1260:1338 In addition, we also confirmed a small amount of unexpected Man6GlcNAc2 intermediate from delta och1delta alg3 delta mnnl strain. 25199249 9 53 theme intermediate 1283:1294 arg1 amount 1250:1255 a small amount 1242:1255 a small amount of unexpected Man6GlcNAc2 intermediate from delta och1delta alg3 delta mnnl strain 1242:1338 In addition, we also confirmed a small amount of unexpected Man6GlcNAc2 intermediate from delta och1delta alg3 delta mnnl strain. 25199249 7 54 theme N-glycosylation 1056:1070 arg1 intermediate 1034:1045 Man5 GlcNAc2 intermediate 1021:1045 Man5 GlcNAc2 intermediate of human N-glycosylation 1021:1070 RESULTS & CONCLUSION We obtained a delta och1 delta alg3 delta mnn1 strain that produces Man5 GlcNAc2 intermediate of human N-glycosylation. 25199249 1 55 theme human 128:132 arg1 glycoproteins 134:146 human glycoproteins 128:146 human glycoproteins in Saccharomyces cerevisiae 128:174 OBJECTIVE To produce human glycoproteins in Saccharomyces cerevisiae, human N-glycosylation pathway must be genetically engineered into the yeast cell. 25199249 9 56 from amount 1250:1255 arg1 strain 1333:1338 delta och1delta alg3 delta mnnl strain 1301:1338 delta och1delta alg3 delta mnnl strain 1301:1338 In addition, we also confirmed a small amount of unexpected Man6GlcNAc2 intermediate from delta och1delta alg3 delta mnnl strain. 25199249 9 57 theme delta 1301:1305 arg1 strain 1333:1338 delta och1delta alg3 delta mnnl strain 1301:1338 delta och1delta alg3 delta mnnl strain 1301:1338 In addition, we also confirmed a small amount of unexpected Man6GlcNAc2 intermediate from delta och1delta alg3 delta mnnl strain. 25199249 9 58 theme alg3 1317:1320 arg1 strain 1333:1338 delta och1delta alg3 delta mnnl strain 1301:1338 delta och1delta alg3 delta mnnl strain 1301:1338 In addition, we also confirmed a small amount of unexpected Man6GlcNAc2 intermediate from delta och1delta alg3 delta mnnl strain. 25199249 7 59 theme GlcNAc2 1026:1032 arg1 intermediate 1034:1045 Man5 GlcNAc2 intermediate 1021:1045 Man5 GlcNAc2 intermediate of human N-glycosylation 1021:1070 RESULTS & CONCLUSION We obtained a delta och1 delta alg3 delta mnn1 strain that produces Man5 GlcNAc2 intermediate of human N-glycosylation. 25199249 8 60 from improvement 1131:1141 arg1 phenotype 1157:1165 the growth phenotype 1146:1165 the growth phenotype of delta och1 delta alg3 delta mnn1 strain 1146:1208 Our approach for adaptive evolution resulted a remarkable improvement on the growth phenotype of delta och1 delta alg3 delta mnn1 strain. 25199249 4 61 theme METHODS 546:552 arg1 MNN1 587:590 MNN1 587:590 MNN1 587:590 METHODS Three yeast genes ALG3, OCH1 and MNN1 were disrupted. 25199249 4 61 theme METHODS 546:552 arg1 genes 566:570 METHODS Three yeast genes ALG3, OCH1 and MNN1 546:590 METHODS Three yeast genes ALG3, OCH1 and MNN1 546:590 METHODS Three yeast genes ALG3, OCH1 and MNN1 were disrupted. 25199249 4 61 theme METHODS 546:552 arg1 OCH1 578:581 OCH1 578:581 OCH1 578:581 METHODS Three yeast genes ALG3, OCH1 and MNN1 were disrupted. 25199249 4 61 theme METHODS 546:552 arg1 ALG3 572:575 ALG3 572:575 ALG3 572:575 METHODS Three yeast genes ALG3, OCH1 and MNN1 were disrupted. 25199249 9 62 theme mnnl 1328:1331 arg1 strain 1333:1338 delta och1delta alg3 delta mnnl strain 1301:1338 delta och1delta alg3 delta mnnl strain 1301:1338 In addition, we also confirmed a small amount of unexpected Man6GlcNAc2 intermediate from delta och1delta alg3 delta mnnl strain. 25199249 1 63 theme human 177:181 arg1 pathway 199:205 human N-glycosylation pathway 177:205 human N-glycosylation pathway 177:205 OBJECTIVE To produce human glycoproteins in Saccharomyces cerevisiae, human N-glycosylation pathway must be genetically engineered into the yeast cell. 25199249 4 64 theme yeast 560:564 arg1 MNN1 587:590 MNN1 587:590 MNN1 587:590 METHODS Three yeast genes ALG3, OCH1 and MNN1 were disrupted. 25199249 4 64 theme yeast 560:564 arg1 genes 566:570 METHODS Three yeast genes ALG3, OCH1 and MNN1 546:590 METHODS Three yeast genes ALG3, OCH1 and MNN1 546:590 METHODS Three yeast genes ALG3, OCH1 and MNN1 were disrupted. 25199249 4 64 theme yeast 560:564 arg1 OCH1 578:581 OCH1 578:581 OCH1 578:581 METHODS Three yeast genes ALG3, OCH1 and MNN1 were disrupted. 25199249 4 64 theme yeast 560:564 arg1 ALG3 572:575 ALG3 572:575 ALG3 572:575 METHODS Three yeast genes ALG3, OCH1 and MNN1 were disrupted. 25199249 5 65 theme high-performance 758:773 arg1 chromatography 782:795 high-performance liquid chromatography 758:795 high-performance liquid chromatography (HPLC) 758:802 The N-linked oligosaccharides from the mutant cells were analyzed by the activity staining of invertase, and their structure was further confirmed by high-performance liquid chromatography (HPLC) and the treatment with glycosidase. 25199249 5 65 theme high-performance 758:773 arg1 HPLC 798:801 HPLC 798:801 HPLC 798:801 The N-linked oligosaccharides from the mutant cells were analyzed by the activity staining of invertase, and their structure was further confirmed by high-performance liquid chromatography (HPLC) and the treatment with glycosidase. 25199249 4 66 dep genes 566:570 arg1 MNN1 587:590 MNN1 587:590 MNN1 587:590 METHODS Three yeast genes ALG3, OCH1 and MNN1 were disrupted. 25199249 4 66 dep genes 566:570 arg1 genes 566:570 METHODS Three yeast genes ALG3, OCH1 and MNN1 546:590 METHODS Three yeast genes ALG3, OCH1 and MNN1 546:590 METHODS Three yeast genes ALG3, OCH1 and MNN1 were disrupted. 25199249 4 66 dep genes 566:570 arg1 OCH1 578:581 OCH1 578:581 OCH1 578:581 METHODS Three yeast genes ALG3, OCH1 and MNN1 were disrupted. 25199249 4 66 dep genes 566:570 arg1 ALG3 572:575 ALG3 572:575 ALG3 572:575 METHODS Three yeast genes ALG3, OCH1 and MNN1 were disrupted. 25199249 5 67 theme mutant 647:652 arg1 cells 654:658 the mutant cells 643:658 the mutant cells 643:658 The N-linked oligosaccharides from the mutant cells were analyzed by the activity staining of invertase, and their structure was further confirmed by high-performance liquid chromatography (HPLC) and the treatment with glycosidase. 25199249 0 68 from glycoproteins 63:75 arg1 cerevisiae 94:103 Saccharomyces cerevisiae 80:103 Saccharomyces cerevisiae 80:103 [Reconstruction of N-glycosylation pathway for producing human glycoproteins in Saccharomyces cerevisiae]. 25199249 11 69 theme N-glycosylation 1792:1806 arg1 pathway 1808:1814 human N-glycosylation pathway 1786:1814 human N-glycosylation pathway 1786:1814 Our results demonstrate that delta och1 delta alg3 deltamnn1 triple mutant can be used as an initial strain to construct an yeast therapeutic glycoprotein-expression system by introducing various enzymes that are involved in human N-glycosylation pathway. 25199249 7 70 theme delta 989:993 arg1 strain 1000:1005 a delta och1 delta alg3 delta mnn1 strain 965:1005 a delta och1 delta alg3 delta mnn1 strain that produces Man5 GlcNAc2 intermediate of human N-glycosylation 965:1070 RESULTS & CONCLUSION We obtained a delta och1 delta alg3 delta mnn1 strain that produces Man5 GlcNAc2 intermediate of human N-glycosylation. 25199249 2 71 theme N-glycosylation 415:429 arg1 pathway 431:437 yeast N-glycosylation pathway 409:437 yeast N-glycosylation pathway 409:437 We tried to construct a strain, which can be used to introduce human N-glycosylation reactions, by disrupting several special glycosyltransferases in yeast N-glycosylation pathway. 25199249 7 72 theme delta 978:982 arg1 strain 1000:1005 a delta och1 delta alg3 delta mnn1 strain 965:1005 a delta och1 delta alg3 delta mnn1 strain that produces Man5 GlcNAc2 intermediate of human N-glycosylation 965:1070 RESULTS & CONCLUSION We obtained a delta och1 delta alg3 delta mnn1 strain that produces Man5 GlcNAc2 intermediate of human N-glycosylation. 25199249 0 73 theme pathway 35:41 arg1 [Reconstruction 0:14 [Reconstruction 0:14 [Reconstruction of N-glycosylation pathway for producing human glycoproteins in Saccharomyces cerevisiae 0:103 [Reconstruction of N-glycosylation pathway for producing human glycoproteins in Saccharomyces cerevisiae]. 25199249 1 74 from glycoproteins 134:146 arg1 cerevisiae 165:174 Saccharomyces cerevisiae 151:174 Saccharomyces cerevisiae 151:174 OBJECTIVE To produce human glycoproteins in Saccharomyces cerevisiae, human N-glycosylation pathway must be genetically engineered into the yeast cell. 25199249 11 75 theme glycoprotein-expression 1703:1725 arg1 system 1727:1732 an yeast therapeutic glycoprotein-expression system 1682:1732 an yeast therapeutic glycoprotein-expression system 1682:1732 Our results demonstrate that delta och1 delta alg3 deltamnn1 triple mutant can be used as an initial strain to construct an yeast therapeutic glycoprotein-expression system by introducing various enzymes that are involved in human N-glycosylation pathway. 25199249 6 76 theme adaptive 902:909 arg1 evolution 911:919 their adaptive evolution 896:919 their adaptive evolution of growth 896:929 Mutant cells were cultured under a high temperature for their adaptive evolution of growth. 25199249 11 77 theme yeast 1685:1689 arg1 system 1727:1732 an yeast therapeutic glycoprotein-expression system 1682:1732 an yeast therapeutic glycoprotein-expression system 1682:1732 Our results demonstrate that delta och1 delta alg3 deltamnn1 triple mutant can be used as an initial strain to construct an yeast therapeutic glycoprotein-expression system by introducing various enzymes that are involved in human N-glycosylation pathway. 25199249 11 78 theme alg3 1607:1610 arg1 mutant 1629:1634 delta och1 delta alg3 deltamnn1 triple mutant 1590:1634 delta och1 delta alg3 deltamnn1 triple mutant 1590:1634 Our results demonstrate that delta och1 delta alg3 deltamnn1 triple mutant can be used as an initial strain to construct an yeast therapeutic glycoprotein-expression system by introducing various enzymes that are involved in human N-glycosylation pathway. 25199249 11 78 theme alg3 1607:1610 arg1 strain 1662:1667 an initial strain 1651:1667 an initial strain 1651:1667 Our results demonstrate that delta och1 delta alg3 deltamnn1 triple mutant can be used as an initial strain to construct an yeast therapeutic glycoprotein-expression system by introducing various enzymes that are involved in human N-glycosylation pathway. 25199249 3 79 theme adaptive 486:493 arg1 evolution 495:503 adaptive evolution 486:503 adaptive evolution 486:503 Furthermore, this mutant cell was applied for adaptive evolution to overcome its growth-defect phenotype. 25199249 11 80 theme various 1749:1755 arg1 enzymes 1757:1763 various enzymes 1749:1763 various enzymes that are involved in human N-glycosylation pathway 1749:1814 Our results demonstrate that delta och1 delta alg3 deltamnn1 triple mutant can be used as an initial strain to construct an yeast therapeutic glycoprotein-expression system by introducing various enzymes that are involved in human N-glycosylation pathway. 25199249 10 81 with Treatment 1341:1349 arg1 alpha-1,2-mannosidase 1356:1376 alpha-1,2-mannosidase 1356:1376 alpha-1,2-mannosidase 1356:1376 Treatment with alpha-1,2-mannosidase converted both Man,GlcNAc2 and Man,GlcNAc2 products to a single Man3GlcNAc, form, indicating that the additional mannose on Man,GlcNAc, product comes from an alpha-1, 2 modification. 25199249 11 82 theme och1 1596:1599 arg1 mutant 1629:1634 delta och1 delta alg3 deltamnn1 triple mutant 1590:1634 delta och1 delta alg3 deltamnn1 triple mutant 1590:1634 Our results demonstrate that delta och1 delta alg3 deltamnn1 triple mutant can be used as an initial strain to construct an yeast therapeutic glycoprotein-expression system by introducing various enzymes that are involved in human N-glycosylation pathway. 25199249 11 82 theme och1 1596:1599 arg1 strain 1662:1667 an initial strain 1651:1667 an initial strain 1651:1667 Our results demonstrate that delta och1 delta alg3 deltamnn1 triple mutant can be used as an initial strain to construct an yeast therapeutic glycoprotein-expression system by introducing various enzymes that are involved in human N-glycosylation pathway. 25199249 8 83 theme delta 1170:1174 arg1 strain 1203:1208 delta och1 delta alg3 delta mnn1 strain 1170:1208 delta och1 delta alg3 delta mnn1 strain 1170:1208 Our approach for adaptive evolution resulted a remarkable improvement on the growth phenotype of delta och1 delta alg3 delta mnn1 strain. 25199249 6 84 theme high 875:878 arg1 temperature 880:890 a high temperature 873:890 a high temperature for their adaptive evolution of growth 873:929 Mutant cells were cultured under a high temperature for their adaptive evolution of growth. 25199249 10 85 theme GlcNAc2 1413:1419 arg1 Man 1409:1411 Man 1409:1411 Man 1409:1411 Treatment with alpha-1,2-mannosidase converted both Man,GlcNAc2 and Man,GlcNAc2 products to a single Man3GlcNAc, form, indicating that the additional mannose on Man,GlcNAc, product comes from an alpha-1, 2 modification. 25199249 10 85 theme GlcNAc2 1413:1419 arg1 products 1421:1428 GlcNAc2 products 1413:1428 GlcNAc2 products 1413:1428 Treatment with alpha-1,2-mannosidase converted both Man,GlcNAc2 and Man,GlcNAc2 products to a single Man3GlcNAc, form, indicating that the additional mannose on Man,GlcNAc, product comes from an alpha-1, 2 modification. 25199249 2 86 theme N-glycosylation 328:342 arg1 reactions 344:352 human N-glycosylation reactions 322:352 human N-glycosylation reactions 322:352 We tried to construct a strain, which can be used to introduce human N-glycosylation reactions, by disrupting several special glycosyltransferases in yeast N-glycosylation pathway. 25199249 8 87 theme delta 1181:1185 arg1 strain 1203:1208 delta och1 delta alg3 delta mnn1 strain 1170:1208 delta och1 delta alg3 delta mnn1 strain 1170:1208 Our approach for adaptive evolution resulted a remarkable improvement on the growth phenotype of delta och1 delta alg3 delta mnn1 strain. 25199249 11 88 theme triple 1622:1627 arg1 mutant 1629:1634 delta och1 delta alg3 deltamnn1 triple mutant 1590:1634 delta och1 delta alg3 deltamnn1 triple mutant 1590:1634 Our results demonstrate that delta och1 delta alg3 deltamnn1 triple mutant can be used as an initial strain to construct an yeast therapeutic glycoprotein-expression system by introducing various enzymes that are involved in human N-glycosylation pathway. 25199249 11 88 theme triple 1622:1627 arg1 strain 1662:1667 an initial strain 1651:1667 an initial strain 1651:1667 Our results demonstrate that delta och1 delta alg3 deltamnn1 triple mutant can be used as an initial strain to construct an yeast therapeutic glycoprotein-expression system by introducing various enzymes that are involved in human N-glycosylation pathway. 25199249 2 89 theme special 377:383 arg1 glycosyltransferases 385:404 several special glycosyltransferases 369:404 several special glycosyltransferases 369:404 We tried to construct a strain, which can be used to introduce human N-glycosylation reactions, by disrupting several special glycosyltransferases in yeast N-glycosylation pathway. 25071735 0 0 theme infected 103:110 arg1 cells 112:116 infected cells 103:116 infected cells 103:116 Varicella-zoster virus glycoprotein expression differentially induces the unfolded protein response in infected cells. 25071735 5 1 gly glycosylation 901:913 arg1 ER 922:923 the ER 918:923 the ER 918:923 Tunicamycin is a mixture of chemicals that inhibits N-linked glycosylation in the ER with resultant protein misfolding and the UPR. 25071735 4 2 theme uninfected 789:798 arg1 cells 811:815 uninfected, untreated cells 789:815 uninfected, untreated cells as a negative control 789:837 Herein we report the results of a UPR specific PCR array that measures the levels of mRNA of 84 different components of the UPR in VZV infected cells as compared to tunicamycin treated cells as a positive control and uninfected, untreated cells as a negative control. 25071735 7 3 theme elements 1152:1159 arg1 half 1134:1137 roughly half 1126:1137 roughly half of the array elements 1126:1159 For example, tunicamycin treatment moderately increased (8-fold) roughly half of the array elements while downregulating only three (one ERAD and two FOLD components). 25071735 5 4 from glycosylation 901:913 arg1 ER 922:923 the ER 918:923 the ER 918:923 Tunicamycin is a mixture of chemicals that inhibits N-linked glycosylation in the ER with resultant protein misfolding and the UPR. 25071735 7 5 dep three 1187:1191 arg1 components 1216:1225 two FOLD components 1207:1225 two FOLD components 1207:1225 For example, tunicamycin treatment moderately increased (8-fold) roughly half of the array elements while downregulating only three (one ERAD and two FOLD components). 25071735 7 5 dep three 1187:1191 arg1 ERAD 1198:1201 one ERAD 1194:1201 one ERAD 1194:1201 For example, tunicamycin treatment moderately increased (8-fold) roughly half of the array elements while downregulating only three (one ERAD and two FOLD components). 25071735 9 6 theme glycoprotein 1701:1712 arg1 synthesis 1714:1722 abundant viral glycoprotein synthesis 1686:1722 abundant viral glycoprotein synthesis 1686:1722 We hypothesize that this expression pattern is associated with an expanding ER with downregulation of active degradation by ERAD and apoptosis as the cell attempts to handle abundant viral glycoprotein synthesis. 25071735 8 7 theme VZV 1229:1231 arg1 infection 1233:1241 VZV infection 1229:1241 VZV infection on the other hand 1229:1259 VZV infection on the other hand upregulated 33 components including a little described stress sensor CREB-H (64-fold) as well as ER membrane components INSIG and gp78, which modulate cholesterol synthesis while downregulating over 20 components mostly associated with ERAD and FOLD. 25071735 5 8 link N-linked 892:899 arg1 glycosylation 901:913 N-linked glycosylation 892:913 N-linked glycosylation in the ER with resultant protein misfolding and the UPR 892:969 Tunicamycin is a mixture of chemicals that inhibits N-linked glycosylation in the ER with resultant protein misfolding and the UPR. 25071735 8 9 theme sensor 1323:1328 arg1 CREB-H 1330:1335 a little described stress sensor CREB-H 1297:1335 a little described stress sensor CREB-H (64-fold) 1297:1345 VZV infection on the other hand upregulated 33 components including a little described stress sensor CREB-H (64-fold) as well as ER membrane components INSIG and gp78, which modulate cholesterol synthesis while downregulating over 20 components mostly associated with ERAD and FOLD. 25071735 8 9 theme sensor 1323:1328 arg1 64-fold 1338:1344 64-fold 1338:1344 64-fold 1338:1344 VZV infection on the other hand upregulated 33 components including a little described stress sensor CREB-H (64-fold) as well as ER membrane components INSIG and gp78, which modulate cholesterol synthesis while downregulating over 20 components mostly associated with ERAD and FOLD. 25071735 8 10 theme stress 1316:1321 arg1 CREB-H 1330:1335 a little described stress sensor CREB-H 1297:1335 a little described stress sensor CREB-H (64-fold) 1297:1345 VZV infection on the other hand upregulated 33 components including a little described stress sensor CREB-H (64-fold) as well as ER membrane components INSIG and gp78, which modulate cholesterol synthesis while downregulating over 20 components mostly associated with ERAD and FOLD. 25071735 8 10 theme stress 1316:1321 arg1 64-fold 1338:1344 64-fold 1338:1344 64-fold 1338:1344 VZV infection on the other hand upregulated 33 components including a little described stress sensor CREB-H (64-fold) as well as ER membrane components INSIG and gp78, which modulate cholesterol synthesis while downregulating over 20 components mostly associated with ERAD and FOLD. 25071735 4 11 theme UPR 696:698 arg1 components 678:687 84 different components 665:687 84 different components of the UPR in VZV infected cells 665:720 Herein we report the results of a UPR specific PCR array that measures the levels of mRNA of 84 different components of the UPR in VZV infected cells as compared to tunicamycin treated cells as a positive control and uninfected, untreated cells as a negative control. 25071735 4 12 theme components 678:687 arg1 mRNA 657:660 mRNA 657:660 mRNA of 84 different components of the UPR in VZV infected cells 657:720 Herein we report the results of a UPR specific PCR array that measures the levels of mRNA of 84 different components of the UPR in VZV infected cells as compared to tunicamycin treated cells as a positive control and uninfected, untreated cells as a negative control. 25071735 8 13 theme cholesterol 1412:1422 arg1 synthesis 1424:1432 cholesterol synthesis 1412:1432 cholesterol synthesis 1412:1432 VZV infection on the other hand upregulated 33 components including a little described stress sensor CREB-H (64-fold) as well as ER membrane components INSIG and gp78, which modulate cholesterol synthesis while downregulating over 20 components mostly associated with ERAD and FOLD. 25071735 7 14 dep increased 1107:1115 arg1 8-fold 1118:1123 8-fold 1118:1123 8-fold 1118:1123 For example, tunicamycin treatment moderately increased (8-fold) roughly half of the array elements while downregulating only three (one ERAD and two FOLD components). 25071735 4 15 from UPR 696:698 arg1 cells 716:720 VZV infected cells 703:720 VZV infected cells 703:720 Herein we report the results of a UPR specific PCR array that measures the levels of mRNA of 84 different components of the UPR in VZV infected cells as compared to tunicamycin treated cells as a positive control and uninfected, untreated cells as a negative control. 25071735 4 16 theme mRNA 657:660 arg1 levels 647:652 the levels 643:652 the levels of mRNA of 84 different components of the UPR in VZV infected cells 643:720 Herein we report the results of a UPR specific PCR array that measures the levels of mRNA of 84 different components of the UPR in VZV infected cells as compared to tunicamycin treated cells as a positive control and uninfected, untreated cells as a negative control. 25071735 8 17 theme little 1299:1304 arg1 CREB-H 1330:1335 a little described stress sensor CREB-H 1297:1335 a little described stress sensor CREB-H (64-fold) 1297:1345 VZV infection on the other hand upregulated 33 components including a little described stress sensor CREB-H (64-fold) as well as ER membrane components INSIG and gp78, which modulate cholesterol synthesis while downregulating over 20 components mostly associated with ERAD and FOLD. 25071735 8 17 theme little 1299:1304 arg1 64-fold 1338:1344 64-fold 1338:1344 64-fold 1338:1344 VZV infection on the other hand upregulated 33 components including a little described stress sensor CREB-H (64-fold) as well as ER membrane components INSIG and gp78, which modulate cholesterol synthesis while downregulating over 20 components mostly associated with ERAD and FOLD. 25071735 8 18 theme described 1306:1314 arg1 CREB-H 1330:1335 a little described stress sensor CREB-H 1297:1335 a little described stress sensor CREB-H (64-fold) 1297:1345 VZV infection on the other hand upregulated 33 components including a little described stress sensor CREB-H (64-fold) as well as ER membrane components INSIG and gp78, which modulate cholesterol synthesis while downregulating over 20 components mostly associated with ERAD and FOLD. 25071735 8 18 theme described 1306:1314 arg1 64-fold 1338:1344 64-fold 1338:1344 64-fold 1338:1344 VZV infection on the other hand upregulated 33 components including a little described stress sensor CREB-H (64-fold) as well as ER membrane components INSIG and gp78, which modulate cholesterol synthesis while downregulating over 20 components mostly associated with ERAD and FOLD. 25071735 4 19 theme VZV 703:705 arg1 cells 716:720 VZV infected cells 703:720 VZV infected cells 703:720 Herein we report the results of a UPR specific PCR array that measures the levels of mRNA of 84 different components of the UPR in VZV infected cells as compared to tunicamycin treated cells as a positive control and uninfected, untreated cells as a negative control. 25071735 4 20 theme UPR 606:608 arg1 array 623:627 a UPR specific PCR array 604:627 a UPR specific PCR array that measures the levels of mRNA of 84 different components of the UPR in VZV infected cells as compared to tunicamycin treated cells as a positive control and uninfected, untreated cells as a negative control 604:837 Herein we report the results of a UPR specific PCR array that measures the levels of mRNA of 84 different components of the UPR in VZV infected cells as compared to tunicamycin treated cells as a positive control and uninfected, untreated cells as a negative control. 25071735 9 21 theme viral 1695:1699 arg1 synthesis 1714:1722 abundant viral glycoprotein synthesis 1686:1722 abundant viral glycoprotein synthesis 1686:1722 We hypothesize that this expression pattern is associated with an expanding ER with downregulation of active degradation by ERAD and apoptosis as the cell attempts to handle abundant viral glycoprotein synthesis. 25071735 9 22 theme expanding 1578:1586 arg1 ER 1588:1589 an expanding ER 1575:1589 an expanding ER 1575:1589 We hypothesize that this expression pattern is associated with an expanding ER with downregulation of active degradation by ERAD and apoptosis as the cell attempts to handle abundant viral glycoprotein synthesis. 25071735 8 23 from infection 1233:1241 arg1 hand 1256:1259 the other hand 1246:1259 the other hand 1246:1259 VZV infection on the other hand upregulated 33 components including a little described stress sensor CREB-H (64-fold) as well as ER membrane components INSIG and gp78, which modulate cholesterol synthesis while downregulating over 20 components mostly associated with ERAD and FOLD. 25071735 2 24 theme nervous 267:273 arg1 system 275:280 the nervous system 263:280 the nervous system 263:280 The virus then establishes latency in the nervous system and re-emerges, typically decades later, as zoster or shingles. 25071735 8 25 theme ER 1358:1359 arg1 CREB-H 1330:1335 a little described stress sensor CREB-H 1297:1335 a little described stress sensor CREB-H (64-fold) 1297:1345 VZV infection on the other hand upregulated 33 components including a little described stress sensor CREB-H (64-fold) as well as ER membrane components INSIG and gp78, which modulate cholesterol synthesis while downregulating over 20 components mostly associated with ERAD and FOLD. 25071735 8 25 theme ER 1358:1359 arg1 components 1370:1379 ER membrane components 1358:1379 33 components including a little described stress sensor CREB-H (64-fold) as well as ER membrane components INSIG and gp78 1273:1394 VZV infection on the other hand upregulated 33 components including a little described stress sensor CREB-H (64-fold) as well as ER membrane components INSIG and gp78, which modulate cholesterol synthesis while downregulating over 20 components mostly associated with ERAD and FOLD. 25071735 8 25 theme ER 1358:1359 arg1 gp78 1391:1394 gp78 1391:1394 gp78 1391:1394 VZV infection on the other hand upregulated 33 components including a little described stress sensor CREB-H (64-fold) as well as ER membrane components INSIG and gp78, which modulate cholesterol synthesis while downregulating over 20 components mostly associated with ERAD and FOLD. 25071735 8 25 theme ER 1358:1359 arg1 INSIG 1381:1385 INSIG 1381:1385 INSIG 1381:1385 VZV infection on the other hand upregulated 33 components including a little described stress sensor CREB-H (64-fold) as well as ER membrane components INSIG and gp78, which modulate cholesterol synthesis while downregulating over 20 components mostly associated with ERAD and FOLD. 25071735 9 26 theme abundant 1686:1693 arg1 synthesis 1714:1722 abundant viral glycoprotein synthesis 1686:1722 abundant viral glycoprotein synthesis 1686:1722 We hypothesize that this expression pattern is associated with an expanding ER with downregulation of active degradation by ERAD and apoptosis as the cell attempts to handle abundant viral glycoprotein synthesis. 25071735 0 27 theme virus 17:21 arg1 expression 36:45 Varicella-zoster virus glycoprotein expression 0:45 Varicella-zoster virus glycoprotein expression 0:45 Varicella-zoster virus glycoprotein expression differentially induces the unfolded protein response in infected cells. 25071735 4 28 from components 678:687 arg1 cells 716:720 VZV infected cells 703:720 VZV infected cells 703:720 Herein we report the results of a UPR specific PCR array that measures the levels of mRNA of 84 different components of the UPR in VZV infected cells as compared to tunicamycin treated cells as a positive control and uninfected, untreated cells as a negative control. 25071735 4 29 theme different 668:676 arg1 components 678:687 84 different components 665:687 84 different components of the UPR in VZV infected cells 665:720 Herein we report the results of a UPR specific PCR array that measures the levels of mRNA of 84 different components of the UPR in VZV infected cells as compared to tunicamycin treated cells as a positive control and uninfected, untreated cells as a negative control. 25071735 4 30 theme PCR 619:621 arg1 array 623:627 a UPR specific PCR array 604:627 a UPR specific PCR array that measures the levels of mRNA of 84 different components of the UPR in VZV infected cells as compared to tunicamycin treated cells as a positive control and uninfected, untreated cells as a negative control 604:837 Herein we report the results of a UPR specific PCR array that measures the levels of mRNA of 84 different components of the UPR in VZV infected cells as compared to tunicamycin treated cells as a positive control and uninfected, untreated cells as a negative control. 25071735 0 31 theme Varicella-zoster 0:15 arg1 expression 36:45 Varicella-zoster virus glycoprotein expression 0:45 Varicella-zoster virus glycoprotein expression 0:45 Varicella-zoster virus glycoprotein expression differentially induces the unfolded protein response in infected cells. 25071735 4 32 theme positive 768:775 arg1 control 777:783 a positive control 766:783 a positive control 766:783 Herein we report the results of a UPR specific PCR array that measures the levels of mRNA of 84 different components of the UPR in VZV infected cells as compared to tunicamycin treated cells as a positive control and uninfected, untreated cells as a negative control. 25071735 4 33 theme specific 610:617 arg1 array 623:627 a UPR specific PCR array 604:627 a UPR specific PCR array that measures the levels of mRNA of 84 different components of the UPR in VZV infected cells as compared to tunicamycin treated cells as a positive control and uninfected, untreated cells as a negative control 604:837 Herein we report the results of a UPR specific PCR array that measures the levels of mRNA of 84 different components of the UPR in VZV infected cells as compared to tunicamycin treated cells as a positive control and uninfected, untreated cells as a negative control. 25071735 7 34 theme tunicamycin 1074:1084 arg1 treatment 1086:1094 tunicamycin treatment 1074:1094 tunicamycin treatment 1074:1094 For example, tunicamycin treatment moderately increased (8-fold) roughly half of the array elements while downregulating only three (one ERAD and two FOLD components). 25071735 8 35 dep components 1370:1379 arg1 CREB-H 1330:1335 a little described stress sensor CREB-H 1297:1335 a little described stress sensor CREB-H (64-fold) 1297:1345 VZV infection on the other hand upregulated 33 components including a little described stress sensor CREB-H (64-fold) as well as ER membrane components INSIG and gp78, which modulate cholesterol synthesis while downregulating over 20 components mostly associated with ERAD and FOLD. 25071735 8 35 dep components 1370:1379 arg1 components 1370:1379 ER membrane components 1358:1379 33 components including a little described stress sensor CREB-H (64-fold) as well as ER membrane components INSIG and gp78 1273:1394 VZV infection on the other hand upregulated 33 components including a little described stress sensor CREB-H (64-fold) as well as ER membrane components INSIG and gp78, which modulate cholesterol synthesis while downregulating over 20 components mostly associated with ERAD and FOLD. 25071735 8 35 dep components 1370:1379 arg1 gp78 1391:1394 gp78 1391:1394 gp78 1391:1394 VZV infection on the other hand upregulated 33 components including a little described stress sensor CREB-H (64-fold) as well as ER membrane components INSIG and gp78, which modulate cholesterol synthesis while downregulating over 20 components mostly associated with ERAD and FOLD. 25071735 8 35 dep components 1370:1379 arg1 INSIG 1381:1385 INSIG 1381:1385 INSIG 1381:1385 VZV infection on the other hand upregulated 33 components including a little described stress sensor CREB-H (64-fold) as well as ER membrane components INSIG and gp78, which modulate cholesterol synthesis while downregulating over 20 components mostly associated with ERAD and FOLD. 25071735 4 36 theme treated 749:755 arg1 cells 757:761 tunicamycin treated cells 737:761 tunicamycin treated cells as a positive control 737:783 Herein we report the results of a UPR specific PCR array that measures the levels of mRNA of 84 different components of the UPR in VZV infected cells as compared to tunicamycin treated cells as a positive control and uninfected, untreated cells as a negative control. 25071735 3 37 theme expanded 515:522 arg1 ER 547:548 ER 547:548 ER 547:548 We have reported previously that VZV induces autophagy in infected cells as well as exhibiting evidence of the Unfolded Protein Response (UPR): XBP1 splicing, a greatly expanded Endoplasmic Reticulum (ER) and CHOP expression. 25071735 3 37 theme expanded 515:522 arg1 Reticulum 536:544 a greatly expanded Endoplasmic Reticulum 505:544 a greatly expanded Endoplasmic Reticulum (ER) 505:549 We have reported previously that VZV induces autophagy in infected cells as well as exhibiting evidence of the Unfolded Protein Response (UPR): XBP1 splicing, a greatly expanded Endoplasmic Reticulum (ER) and CHOP expression. 25071735 5 38 theme resultant 930:938 arg1 misfolding 948:957 resultant protein misfolding 930:957 resultant protein misfolding 930:957 Tunicamycin is a mixture of chemicals that inhibits N-linked glycosylation in the ER with resultant protein misfolding and the UPR. 25071735 7 39 theme FOLD 1211:1214 arg1 components 1216:1225 two FOLD components 1207:1225 two FOLD components 1207:1225 For example, tunicamycin treatment moderately increased (8-fold) roughly half of the array elements while downregulating only three (one ERAD and two FOLD components). 25071735 0 40 theme glycoprotein 23:34 arg1 expression 36:45 Varicella-zoster virus glycoprotein expression 0:45 Varicella-zoster virus glycoprotein expression 0:45 Varicella-zoster virus glycoprotein expression differentially induces the unfolded protein response in infected cells. 25071735 5 41 theme N-linked 892:899 arg1 glycosylation 901:913 N-linked glycosylation 892:913 N-linked glycosylation in the ER with resultant protein misfolding and the UPR 892:969 Tunicamycin is a mixture of chemicals that inhibits N-linked glycosylation in the ER with resultant protein misfolding and the UPR. 25071735 3 42 theme Endoplasmic 524:534 arg1 ER 547:548 ER 547:548 ER 547:548 We have reported previously that VZV induces autophagy in infected cells as well as exhibiting evidence of the Unfolded Protein Response (UPR): XBP1 splicing, a greatly expanded Endoplasmic Reticulum (ER) and CHOP expression. 25071735 3 42 theme Endoplasmic 524:534 arg1 Reticulum 536:544 a greatly expanded Endoplasmic Reticulum 505:544 a greatly expanded Endoplasmic Reticulum (ER) 505:549 We have reported previously that VZV induces autophagy in infected cells as well as exhibiting evidence of the Unfolded Protein Response (UPR): XBP1 splicing, a greatly expanded Endoplasmic Reticulum (ER) and CHOP expression. 25071735 9 43 theme active 1614:1619 arg1 degradation 1621:1631 active degradation 1614:1631 active degradation by ERAD 1614:1639 We hypothesize that this expression pattern is associated with an expanding ER with downregulation of active degradation by ERAD and apoptosis as the cell attempts to handle abundant viral glycoprotein synthesis. 25071735 3 44 dep cells 413:417 arg1 exhibiting 430:439 exhibiting 430:439 as well as exhibiting evidence of the Unfolded Protein Response (UPR): XBP1 splicing, a greatly expanded Endoplasmic Reticulum (ER) and CHOP expression 419:569 We have reported previously that VZV induces autophagy in infected cells as well as exhibiting evidence of the Unfolded Protein Response (UPR): XBP1 splicing, a greatly expanded Endoplasmic Reticulum (ER) and CHOP expression. 25071735 8 45 dep upregulated 1261:1271 arg1 modulate 1403:1410 modulate 1403:1410 modulate cholesterol synthesis while downregulating over 20 components mostly associated with ERAD and FOLD 1403:1509 VZV infection on the other hand upregulated 33 components including a little described stress sensor CREB-H (64-fold) as well as ER membrane components INSIG and gp78, which modulate cholesterol synthesis while downregulating over 20 components mostly associated with ERAD and FOLD. 25071735 3 46 theme infected 404:411 arg1 cells 413:417 infected cells 404:417 infected cells as well as exhibiting evidence of the Unfolded Protein Response (UPR): XBP1 splicing, a greatly expanded Endoplasmic Reticulum (ER) and CHOP expression 404:569 We have reported previously that VZV induces autophagy in infected cells as well as exhibiting evidence of the Unfolded Protein Response (UPR): XBP1 splicing, a greatly expanded Endoplasmic Reticulum (ER) and CHOP expression. 25071735 5 47 with glycosylation 901:913 arg1 misfolding 948:957 resultant protein misfolding 930:957 resultant protein misfolding 930:957 Tunicamycin is a mixture of chemicals that inhibits N-linked glycosylation in the ER with resultant protein misfolding and the UPR. 25071735 5 47 with glycosylation 901:913 arg1 UPR 967:969 the UPR 963:969 the UPR 963:969 Tunicamycin is a mixture of chemicals that inhibits N-linked glycosylation in the ER with resultant protein misfolding and the UPR. 25071735 0 48 from response 91:98 arg1 cells 112:116 infected cells 103:116 infected cells 103:116 Varicella-zoster virus glycoprotein expression differentially induces the unfolded protein response in infected cells. 25071735 3 49 theme CHOP 555:558 arg1 expression 560:569 CHOP expression 555:569 CHOP expression 555:569 We have reported previously that VZV induces autophagy in infected cells as well as exhibiting evidence of the Unfolded Protein Response (UPR): XBP1 splicing, a greatly expanded Endoplasmic Reticulum (ER) and CHOP expression. 25071735 0 50 theme unfolded 74:81 arg1 response 91:98 the unfolded protein response 70:98 the unfolded protein response in infected cells 70:116 Varicella-zoster virus glycoprotein expression differentially induces the unfolded protein response in infected cells. 25071735 7 51 theme array 1146:1150 arg1 elements 1152:1159 the array elements 1142:1159 the array elements 1142:1159 For example, tunicamycin treatment moderately increased (8-fold) roughly half of the array elements while downregulating only three (one ERAD and two FOLD components). 25071735 0 52 gly glycoprotein 23:34 arg1 glycoprotein 23:34 Varicella-zoster virus glycoprotein expression 0:45 Varicella-zoster virus glycoprotein expression 0:45 Varicella-zoster virus glycoprotein expression differentially induces the unfolded protein response in infected cells. 25071735 3 53 theme Response 474:481 arg1 evidence 441:448 evidence 441:448 evidence of the Unfolded Protein Response (UPR) 441:487 We have reported previously that VZV induces autophagy in infected cells as well as exhibiting evidence of the Unfolded Protein Response (UPR): XBP1 splicing, a greatly expanded Endoplasmic Reticulum (ER) and CHOP expression. 25071735 9 54 theme degradation 1621:1631 arg1 downregulation 1596:1609 downregulation 1596:1609 downregulation of active degradation by ERAD 1596:1639 We hypothesize that this expression pattern is associated with an expanding ER with downregulation of active degradation by ERAD and apoptosis as the cell attempts to handle abundant viral glycoprotein synthesis. 25071735 9 54 theme degradation 1621:1631 arg1 apoptosis 1645:1653 apoptosis 1645:1653 apoptosis 1645:1653 We hypothesize that this expression pattern is associated with an expanding ER with downregulation of active degradation by ERAD and apoptosis as the cell attempts to handle abundant viral glycoprotein synthesis. 25071735 4 55 dep uninfected 789:798 arg1 untreated 801:809 untreated 801:809 untreated 801:809 Herein we report the results of a UPR specific PCR array that measures the levels of mRNA of 84 different components of the UPR in VZV infected cells as compared to tunicamycin treated cells as a positive control and uninfected, untreated cells as a negative control. 25071735 8 56 theme membrane 1361:1368 arg1 CREB-H 1330:1335 a little described stress sensor CREB-H 1297:1335 a little described stress sensor CREB-H (64-fold) 1297:1345 VZV infection on the other hand upregulated 33 components including a little described stress sensor CREB-H (64-fold) as well as ER membrane components INSIG and gp78, which modulate cholesterol synthesis while downregulating over 20 components mostly associated with ERAD and FOLD. 25071735 8 56 theme membrane 1361:1368 arg1 components 1370:1379 ER membrane components 1358:1379 33 components including a little described stress sensor CREB-H (64-fold) as well as ER membrane components INSIG and gp78 1273:1394 VZV infection on the other hand upregulated 33 components including a little described stress sensor CREB-H (64-fold) as well as ER membrane components INSIG and gp78, which modulate cholesterol synthesis while downregulating over 20 components mostly associated with ERAD and FOLD. 25071735 8 56 theme membrane 1361:1368 arg1 gp78 1391:1394 gp78 1391:1394 gp78 1391:1394 VZV infection on the other hand upregulated 33 components including a little described stress sensor CREB-H (64-fold) as well as ER membrane components INSIG and gp78, which modulate cholesterol synthesis while downregulating over 20 components mostly associated with ERAD and FOLD. 25071735 8 56 theme membrane 1361:1368 arg1 INSIG 1381:1385 INSIG 1381:1385 INSIG 1381:1385 VZV infection on the other hand upregulated 33 components including a little described stress sensor CREB-H (64-fold) as well as ER membrane components INSIG and gp78, which modulate cholesterol synthesis while downregulating over 20 components mostly associated with ERAD and FOLD. 25071735 1 57 theme human 153:157 arg1 herpesvirus 159:169 a human herpesvirus 151:169 a human herpesvirus that spreads to children as varicella or chicken pox 151:222 Varicella-zoster virus (VZV) is a human herpesvirus that spreads to children as varicella or chicken pox. 25071735 1 57 theme human 153:157 arg1 virus 136:140 Varicella-zoster virus 119:140 Varicella-zoster virus (VZV) 119:146 Varicella-zoster virus (VZV) is a human herpesvirus that spreads to children as varicella or chicken pox. 25071735 6 58 theme tunicamycin 1038:1048 arg1 treatment 1050:1058 tunicamycin treatment 1038:1058 tunicamycin treatment 1038:1058 We found that VZV differentially induces the UPR when compared to tunicamycin treatment. 25071735 4 59 theme negative 822:829 arg1 control 831:837 a negative control 820:837 a negative control 820:837 Herein we report the results of a UPR specific PCR array that measures the levels of mRNA of 84 different components of the UPR in VZV infected cells as compared to tunicamycin treated cells as a positive control and uninfected, untreated cells as a negative control. 25071735 5 60 theme protein 940:946 arg1 misfolding 948:957 resultant protein misfolding 930:957 resultant protein misfolding 930:957 Tunicamycin is a mixture of chemicals that inhibits N-linked glycosylation in the ER with resultant protein misfolding and the UPR. 25071735 4 61 theme array 623:627 arg1 results 593:599 the results 589:599 the results of a UPR specific PCR array that measures the levels of mRNA of 84 different components of the UPR in VZV infected cells as compared to tunicamycin treated cells as a positive control and uninfected, untreated cells as a negative control 589:837 Herein we report the results of a UPR specific PCR array that measures the levels of mRNA of 84 different components of the UPR in VZV infected cells as compared to tunicamycin treated cells as a positive control and uninfected, untreated cells as a negative control. 25071735 3 62 theme Unfolded 457:464 arg1 Response 474:481 the Unfolded Protein Response 453:481 the Unfolded Protein Response (UPR) 453:487 We have reported previously that VZV induces autophagy in infected cells as well as exhibiting evidence of the Unfolded Protein Response (UPR): XBP1 splicing, a greatly expanded Endoplasmic Reticulum (ER) and CHOP expression. 25071735 3 62 theme Unfolded 457:464 arg1 UPR 484:486 UPR 484:486 UPR 484:486 We have reported previously that VZV induces autophagy in infected cells as well as exhibiting evidence of the Unfolded Protein Response (UPR): XBP1 splicing, a greatly expanded Endoplasmic Reticulum (ER) and CHOP expression. 25071735 1 63 theme Varicella-zoster 119:134 arg1 herpesvirus 159:169 a human herpesvirus 151:169 a human herpesvirus that spreads to children as varicella or chicken pox 151:222 Varicella-zoster virus (VZV) is a human herpesvirus that spreads to children as varicella or chicken pox. 25071735 1 63 theme Varicella-zoster 119:134 arg1 VZV 143:145 VZV 143:145 VZV 143:145 Varicella-zoster virus (VZV) is a human herpesvirus that spreads to children as varicella or chicken pox. 25071735 1 63 theme Varicella-zoster 119:134 arg1 virus 136:140 Varicella-zoster virus 119:140 Varicella-zoster virus (VZV) 119:146 Varicella-zoster virus (VZV) is a human herpesvirus that spreads to children as varicella or chicken pox. 25071735 8 64 theme other 1250:1254 arg1 hand 1256:1259 the other hand 1246:1259 the other hand 1246:1259 VZV infection on the other hand upregulated 33 components including a little described stress sensor CREB-H (64-fold) as well as ER membrane components INSIG and gp78, which modulate cholesterol synthesis while downregulating over 20 components mostly associated with ERAD and FOLD. 25071735 4 65 theme infected 707:714 arg1 cells 716:720 VZV infected cells 703:720 VZV infected cells 703:720 Herein we report the results of a UPR specific PCR array that measures the levels of mRNA of 84 different components of the UPR in VZV infected cells as compared to tunicamycin treated cells as a positive control and uninfected, untreated cells as a negative control. 25071735 3 66 theme Protein 466:472 arg1 Response 474:481 the Unfolded Protein Response 453:481 the Unfolded Protein Response (UPR) 453:487 We have reported previously that VZV induces autophagy in infected cells as well as exhibiting evidence of the Unfolded Protein Response (UPR): XBP1 splicing, a greatly expanded Endoplasmic Reticulum (ER) and CHOP expression. 25071735 3 66 theme Protein 466:472 arg1 UPR 484:486 UPR 484:486 UPR 484:486 We have reported previously that VZV induces autophagy in infected cells as well as exhibiting evidence of the Unfolded Protein Response (UPR): XBP1 splicing, a greatly expanded Endoplasmic Reticulum (ER) and CHOP expression. 25071735 1 67 dep varicella 199:207 arg1 pox 220:222 pox 220:222 pox 220:222 Varicella-zoster virus (VZV) is a human herpesvirus that spreads to children as varicella or chicken pox. 25071735 9 68 gly glycoprotein 1701:1712 arg1 glycoprotein 1701:1712 abundant viral glycoprotein synthesis 1686:1722 abundant viral glycoprotein synthesis 1686:1722 We hypothesize that this expression pattern is associated with an expanding ER with downregulation of active degradation by ERAD and apoptosis as the cell attempts to handle abundant viral glycoprotein synthesis. 25071735 5 69 theme chemicals 868:876 arg1 Tunicamycin 840:850 Tunicamycin 840:850 Tunicamycin 840:850 Tunicamycin is a mixture of chemicals that inhibits N-linked glycosylation in the ER with resultant protein misfolding and the UPR. 25071735 5 69 theme chemicals 868:876 arg1 mixture 857:863 a mixture 855:863 a mixture of chemicals that inhibits N-linked glycosylation in the ER with resultant protein misfolding and the UPR 855:969 Tunicamycin is a mixture of chemicals that inhibits N-linked glycosylation in the ER with resultant protein misfolding and the UPR. 25071735 0 70 theme protein 83:89 arg1 response 91:98 the unfolded protein response 70:98 the unfolded protein response in infected cells 70:116 Varicella-zoster virus glycoprotein expression differentially induces the unfolded protein response in infected cells. 25071735 9 71 theme expression 1537:1546 arg1 pattern 1548:1554 this expression pattern 1532:1554 this expression pattern 1532:1554 We hypothesize that this expression pattern is associated with an expanding ER with downregulation of active degradation by ERAD and apoptosis as the cell attempts to handle abundant viral glycoprotein synthesis. 25071735 4 72 from cells 716:720 arg1 components 678:687 84 different components 665:687 84 different components of the UPR in VZV infected cells 665:720 Herein we report the results of a UPR specific PCR array that measures the levels of mRNA of 84 different components of the UPR in VZV infected cells as compared to tunicamycin treated cells as a positive control and uninfected, untreated cells as a negative control. 25071735 3 73 theme XBP1 490:493 arg1 splicing 495:502 XBP1 splicing 490:502 XBP1 splicing 490:502 We have reported previously that VZV induces autophagy in infected cells as well as exhibiting evidence of the Unfolded Protein Response (UPR): XBP1 splicing, a greatly expanded Endoplasmic Reticulum (ER) and CHOP expression. 24618751 6 0 theme absolute 1374:1381 arg1 energies 1393:1400 the absolute collision energies 1370:1400 the absolute collision energies at which either glycan or peptide fragmentations were accessed 1370:1463 While glycopeptide ions having disparate physical and chemical characteristics shared strikingly similar qualitative responses to increasing vibrational energy deposition, the absolute collision energies at which either glycan or peptide fragmentations were accessed varied substantially among the precursor ions examined. 24618751 4 1 theme peptide 891:897 arg1 cleavage 899:906 peptide cleavage 891:906 peptide cleavage 891:906 Unfortunately, the relative energy requirements for glycan and peptide cleavage have not been thoroughly characterized with respect to specific physicochemical characteristics of the precursor ions. 24618751 9 2 theme CID 2064:2066 arg1 capabilities 2048:2059 the capabilities 2044:2059 the capabilities of CID in the context of glycoproteomics 2044:2100 Overall, these results highlight the potential to further extend the capabilities of CID in the context of glycoproteomics. 24618751 8 3 theme online 1780:1785 arg1 modulation 1804:1813 online collision energy modulation 1780:1813 online collision energy modulation 1780:1813 The practical usefulness of these observations was demonstrated through implementation of online collision energy modulation such that both glycan and peptide fragmentation were captured in the same spectrum, providing near-exhaustive glycopeptide characterization in a single experiment. 24618751 4 4 theme relative 847:854 arg1 requirements 863:874 the relative energy requirements 843:874 the relative energy requirements for glycan and peptide cleavage 843:906 Unfortunately, the relative energy requirements for glycan and peptide cleavage have not been thoroughly characterized with respect to specific physicochemical characteristics of the precursor ions. 24618751 6 5 theme disparate 1229:1237 arg1 characteristics 1261:1275 disparate physical and chemical characteristics 1229:1275 disparate physical and chemical characteristics 1229:1275 While glycopeptide ions having disparate physical and chemical characteristics shared strikingly similar qualitative responses to increasing vibrational energy deposition, the absolute collision energies at which either glycan or peptide fragmentations were accessed varied substantially among the precursor ions examined. 24618751 6 6 theme energy 1351:1356 arg1 deposition 1358:1367 increasing vibrational energy deposition 1328:1367 increasing vibrational energy deposition 1328:1367 While glycopeptide ions having disparate physical and chemical characteristics shared strikingly similar qualitative responses to increasing vibrational energy deposition, the absolute collision energies at which either glycan or peptide fragmentations were accessed varied substantially among the precursor ions examined. 24618751 7 7 theme energy 1563:1568 arg1 requirements 1570:1581 the energy requirements 1559:1581 the energy requirements for peptide and glycan cleavage 1559:1613 Nevertheless, these data suggest that the energy requirements for peptide and glycan cleavage may be somewhat predictable based on characteristics of the precursor ion. 24618751 7 7 theme energy 1563:1568 arg1 predictable 1631:1641 predictable 1631:1641 predictable 1631:1641 Nevertheless, these data suggest that the energy requirements for peptide and glycan cleavage may be somewhat predictable based on characteristics of the precursor ion. 24618751 0 8 link N-linked 65:72 arg1 glycopeptides 74:86 model N-linked glycopeptides 59:86 model N-linked glycopeptides 59:86 Energy-resolved collision-induced dissociation pathways of model N-linked glycopeptides: implications for capturing glycan connectivity and peptide sequence in a single experiment. 24618751 6 9 theme increasing 1328:1337 arg1 deposition 1358:1367 increasing vibrational energy deposition 1328:1367 increasing vibrational energy deposition 1328:1367 While glycopeptide ions having disparate physical and chemical characteristics shared strikingly similar qualitative responses to increasing vibrational energy deposition, the absolute collision energies at which either glycan or peptide fragmentations were accessed varied substantially among the precursor ions examined. 24618751 3 10 theme single 578:583 arg1 method 602:607 any single ion dissociation method 574:607 any single ion dissociation method 574:607 This level of detail is often difficult to achieve using any single ion dissociation method; however, precedent does exist for use of collision-induced dissociation (CID) to establish either the connectivity of the oligosaccharide or the sequence of the polypeptide depending upon the applied collision energy. 24618751 3 11 theme oligosaccharide 732:746 arg1 connectivity 712:723 the connectivity 708:723 the connectivity of the oligosaccharide 708:746 This level of detail is often difficult to achieve using any single ion dissociation method; however, precedent does exist for use of collision-induced dissociation (CID) to establish either the connectivity of the oligosaccharide or the sequence of the polypeptide depending upon the applied collision energy. 24618751 3 11 theme oligosaccharide 732:746 arg1 sequence 755:762 the sequence 751:762 the sequence of the polypeptide 751:781 This level of detail is often difficult to achieve using any single ion dissociation method; however, precedent does exist for use of collision-induced dissociation (CID) to establish either the connectivity of the oligosaccharide or the sequence of the polypeptide depending upon the applied collision energy. 24618751 6 12 theme peptide 1428:1434 arg1 fragmentations 1436:1449 either glycan or peptide fragmentations 1411:1449 fragmentations 1436:1449 While glycopeptide ions having disparate physical and chemical characteristics shared strikingly similar qualitative responses to increasing vibrational energy deposition, the absolute collision energies at which either glycan or peptide fragmentations were accessed varied substantially among the precursor ions examined. 24618751 5 13 theme model 1101:1105 arg1 glycopeptides 1115:1127 model tryptic glycopeptides 1101:1127 model tryptic glycopeptides derived from Erythrina cristagalli lectin and bovine ribonuclease B 1101:1195 This report describes case studies on the energy-resolved CID pathways of model tryptic glycopeptides derived from Erythrina cristagalli lectin and bovine ribonuclease B. 24618751 1 14 theme glycopeptides 217:229 arg1 MS/MS 207:211 MS/MS 207:211 MS/MS 207:211 Tandem mass spectrometry (MS/MS) of glycopeptides stands among the principal analytical approaches for assessing protein glycosylation in a site-specific manner. 24618751 1 14 theme glycopeptides 217:229 arg1 spectrometry 193:204 Tandem mass spectrometry 181:204 Tandem mass spectrometry (MS/MS) of glycopeptides 181:229 Tandem mass spectrometry (MS/MS) of glycopeptides stands among the principal analytical approaches for assessing protein glycosylation in a site-specific manner. 24618751 3 15 theme polypeptide 771:781 arg1 connectivity 712:723 the connectivity 708:723 the connectivity of the oligosaccharide 708:746 This level of detail is often difficult to achieve using any single ion dissociation method; however, precedent does exist for use of collision-induced dissociation (CID) to establish either the connectivity of the oligosaccharide or the sequence of the polypeptide depending upon the applied collision energy. 24618751 3 15 theme polypeptide 771:781 arg1 sequence 755:762 the sequence 751:762 the sequence of the polypeptide 751:781 This level of detail is often difficult to achieve using any single ion dissociation method; however, precedent does exist for use of collision-induced dissociation (CID) to establish either the connectivity of the oligosaccharide or the sequence of the polypeptide depending upon the applied collision energy. 24618751 5 16 theme glycopeptides 1115:1127 arg1 pathways 1089:1096 the energy-resolved CID pathways 1065:1096 the energy-resolved CID pathways of model tryptic glycopeptides derived from Erythrina cristagalli lectin and bovine ribonuclease B 1065:1195 This report describes case studies on the energy-resolved CID pathways of model tryptic glycopeptides derived from Erythrina cristagalli lectin and bovine ribonuclease B. 24618751 6 17 theme qualitative 1303:1313 arg1 responses 1315:1323 strikingly similar qualitative responses 1284:1323 strikingly similar qualitative responses to increasing vibrational energy deposition 1284:1367 While glycopeptide ions having disparate physical and chemical characteristics shared strikingly similar qualitative responses to increasing vibrational energy deposition, the absolute collision energies at which either glycan or peptide fragmentations were accessed varied substantially among the precursor ions examined. 24618751 5 18 theme energy-resolved 1069:1083 arg1 pathways 1089:1096 the energy-resolved CID pathways 1065:1096 the energy-resolved CID pathways of model tryptic glycopeptides derived from Erythrina cristagalli lectin and bovine ribonuclease B 1065:1195 This report describes case studies on the energy-resolved CID pathways of model tryptic glycopeptides derived from Erythrina cristagalli lectin and bovine ribonuclease B. 24618751 3 19 theme dissociation 589:600 arg1 method 602:607 any single ion dissociation method 574:607 any single ion dissociation method 574:607 This level of detail is often difficult to achieve using any single ion dissociation method; however, precedent does exist for use of collision-induced dissociation (CID) to establish either the connectivity of the oligosaccharide or the sequence of the polypeptide depending upon the applied collision energy. 24618751 8 20 theme glycopeptide 1925:1936 arg1 characterization 1938:1953 near-exhaustive glycopeptide characterization 1909:1953 near-exhaustive glycopeptide characterization 1909:1953 The practical usefulness of these observations was demonstrated through implementation of online collision energy modulation such that both glycan and peptide fragmentation were captured in the same spectrum, providing near-exhaustive glycopeptide characterization in a single experiment. 24618751 9 21 from context 2075:2081 arg1 capabilities 2048:2059 the capabilities 2044:2059 the capabilities of CID in the context of glycoproteomics 2044:2100 Overall, these results highlight the potential to further extend the capabilities of CID in the context of glycoproteomics. 24618751 3 22 theme applied 802:808 arg1 energy 820:825 the applied collision energy 798:825 the applied collision energy 798:825 This level of detail is often difficult to achieve using any single ion dissociation method; however, precedent does exist for use of collision-induced dissociation (CID) to establish either the connectivity of the oligosaccharide or the sequence of the polypeptide depending upon the applied collision energy. 24618751 6 23 theme precursor 1496:1504 arg1 ions 1506:1509 the precursor ions 1492:1509 the precursor ions examined 1492:1518 While glycopeptide ions having disparate physical and chemical characteristics shared strikingly similar qualitative responses to increasing vibrational energy deposition, the absolute collision energies at which either glycan or peptide fragmentations were accessed varied substantially among the precursor ions examined. 24618751 8 24 theme single 1960:1965 arg1 experiment 1967:1976 a single experiment 1958:1976 a single experiment 1958:1976 The practical usefulness of these observations was demonstrated through implementation of online collision energy modulation such that both glycan and peptide fragmentation were captured in the same spectrum, providing near-exhaustive glycopeptide characterization in a single experiment. 24618751 2 25 theme glycan 498:503 arg1 attachment 505:514 glycan attachment 498:514 glycan attachment 498:514 The aims of such experiments are often to determine the monosaccharide connectivity of the glycan, the amino acid sequence of the peptide, and the site of glycan attachment. 24618751 5 26 theme ribonuclease 1182:1193 arg1 B 1195:1195 bovine ribonuclease B 1175:1195 bovine ribonuclease B 1175:1195 This report describes case studies on the energy-resolved CID pathways of model tryptic glycopeptides derived from Erythrina cristagalli lectin and bovine ribonuclease B. 24618751 1 27 theme mass 188:191 arg1 MS/MS 207:211 MS/MS 207:211 MS/MS 207:211 Tandem mass spectrometry (MS/MS) of glycopeptides stands among the principal analytical approaches for assessing protein glycosylation in a site-specific manner. 24618751 1 27 theme mass 188:191 arg1 spectrometry 193:204 Tandem mass spectrometry 181:204 Tandem mass spectrometry (MS/MS) of glycopeptides 181:229 Tandem mass spectrometry (MS/MS) of glycopeptides stands among the principal analytical approaches for assessing protein glycosylation in a site-specific manner. 24618751 4 28 theme specific 963:970 arg1 characteristics 988:1002 specific physicochemical characteristics 963:1002 specific physicochemical characteristics of the precursor ions 963:1024 Unfortunately, the relative energy requirements for glycan and peptide cleavage have not been thoroughly characterized with respect to specific physicochemical characteristics of the precursor ions. 24618751 0 29 theme glycan 116:121 arg1 connectivity 123:134 glycan connectivity 116:134 glycan connectivity 116:134 Energy-resolved collision-induced dissociation pathways of model N-linked glycopeptides: implications for capturing glycan connectivity and peptide sequence in a single experiment. 24618751 9 30 from CID 2064:2066 arg1 context 2075:2081 the context 2071:2081 the context of glycoproteomics 2071:2100 Overall, these results highlight the potential to further extend the capabilities of CID in the context of glycoproteomics. 24618751 7 31 theme precursor 1675:1683 arg1 ion 1685:1687 the precursor ion 1671:1687 the precursor ion 1671:1687 Nevertheless, these data suggest that the energy requirements for peptide and glycan cleavage may be somewhat predictable based on characteristics of the precursor ion. 24618751 2 32 theme glycan 434:439 arg1 sequence 457:464 the amino acid sequence 442:464 the amino acid sequence of the peptide 442:479 The aims of such experiments are often to determine the monosaccharide connectivity of the glycan, the amino acid sequence of the peptide, and the site of glycan attachment. 24618751 2 32 theme glycan 434:439 arg1 glycan 434:439 the glycan 430:439 the glycan 430:439 The aims of such experiments are often to determine the monosaccharide connectivity of the glycan, the amino acid sequence of the peptide, and the site of glycan attachment. 24618751 2 32 theme glycan 434:439 arg1 peptide 473:479 the peptide 469:479 the peptide 469:479 The aims of such experiments are often to determine the monosaccharide connectivity of the glycan, the amino acid sequence of the peptide, and the site of glycan attachment. 24618751 2 32 theme glycan 434:439 arg1 attachment 505:514 glycan attachment 498:514 glycan attachment 498:514 The aims of such experiments are often to determine the monosaccharide connectivity of the glycan, the amino acid sequence of the peptide, and the site of glycan attachment. 24618751 2 32 theme glycan 434:439 arg1 connectivity 414:425 the monosaccharide connectivity 395:425 the monosaccharide connectivity of the glycan 395:439 The aims of such experiments are often to determine the monosaccharide connectivity of the glycan, the amino acid sequence of the peptide, and the site of glycan attachment. 24618751 2 32 theme glycan 434:439 arg1 site 490:493 the site 486:493 the site of glycan attachment 486:514 The aims of such experiments are often to determine the monosaccharide connectivity of the glycan, the amino acid sequence of the peptide, and the site of glycan attachment. 24618751 5 33 theme cristagalli 1152:1162 arg1 lectin 1164:1169 Erythrina cristagalli lectin 1142:1169 Erythrina cristagalli lectin 1142:1169 This report describes case studies on the energy-resolved CID pathways of model tryptic glycopeptides derived from Erythrina cristagalli lectin and bovine ribonuclease B. 24618751 2 34 theme peptide 473:479 arg1 sequence 457:464 the amino acid sequence 442:464 the amino acid sequence of the peptide 442:479 The aims of such experiments are often to determine the monosaccharide connectivity of the glycan, the amino acid sequence of the peptide, and the site of glycan attachment. 24618751 2 34 theme peptide 473:479 arg1 glycan 434:439 the glycan 430:439 the glycan 430:439 The aims of such experiments are often to determine the monosaccharide connectivity of the glycan, the amino acid sequence of the peptide, and the site of glycan attachment. 24618751 2 34 theme peptide 473:479 arg1 peptide 473:479 the peptide 469:479 the peptide 469:479 The aims of such experiments are often to determine the monosaccharide connectivity of the glycan, the amino acid sequence of the peptide, and the site of glycan attachment. 24618751 2 34 theme peptide 473:479 arg1 attachment 505:514 glycan attachment 498:514 glycan attachment 498:514 The aims of such experiments are often to determine the monosaccharide connectivity of the glycan, the amino acid sequence of the peptide, and the site of glycan attachment. 24618751 2 34 theme peptide 473:479 arg1 connectivity 414:425 the monosaccharide connectivity 395:425 the monosaccharide connectivity of the glycan 395:439 The aims of such experiments are often to determine the monosaccharide connectivity of the glycan, the amino acid sequence of the peptide, and the site of glycan attachment. 24618751 2 34 theme peptide 473:479 arg1 site 490:493 the site 486:493 the site of glycan attachment 486:514 The aims of such experiments are often to determine the monosaccharide connectivity of the glycan, the amino acid sequence of the peptide, and the site of glycan attachment. 24618751 0 35 theme Energy-resolved 0:14 arg1 pathways 47:54 Energy-resolved collision-induced dissociation pathways 0:54 Energy-resolved collision-induced dissociation pathways of model N-linked glycopeptides: implications for capturing glycan connectivity and peptide sequence in a single experiment. 0:179 Energy-resolved collision-induced dissociation pathways of model N-linked glycopeptides: implications for capturing glycan connectivity and peptide sequence in a single experiment. 24618751 1 36 gly glycosylation 302:314 arg1 manner 335:340 a site-specific manner 319:340 a site-specific manner 319:340 Tandem mass spectrometry (MS/MS) of glycopeptides stands among the principal analytical approaches for assessing protein glycosylation in a site-specific manner. 24618751 2 37 theme acid 452:455 arg1 sequence 457:464 the amino acid sequence 442:464 the amino acid sequence of the peptide 442:479 The aims of such experiments are often to determine the monosaccharide connectivity of the glycan, the amino acid sequence of the peptide, and the site of glycan attachment. 24618751 0 38 theme dissociation 34:45 arg1 pathways 47:54 Energy-resolved collision-induced dissociation pathways 0:54 Energy-resolved collision-induced dissociation pathways of model N-linked glycopeptides: implications for capturing glycan connectivity and peptide sequence in a single experiment. 0:179 Energy-resolved collision-induced dissociation pathways of model N-linked glycopeptides: implications for capturing glycan connectivity and peptide sequence in a single experiment. 24618751 1 39 theme site-specific 321:333 arg1 manner 335:340 a site-specific manner 319:340 a site-specific manner 319:340 Tandem mass spectrometry (MS/MS) of glycopeptides stands among the principal analytical approaches for assessing protein glycosylation in a site-specific manner. 24618751 0 40 theme N-linked 65:72 arg1 glycopeptides 74:86 model N-linked glycopeptides 59:86 model N-linked glycopeptides 59:86 Energy-resolved collision-induced dissociation pathways of model N-linked glycopeptides: implications for capturing glycan connectivity and peptide sequence in a single experiment. 24618751 2 41 theme experiments 360:370 arg1 aims 347:350 The aims 343:350 The aims of such experiments 343:370 The aims of such experiments are often to determine the monosaccharide connectivity of the glycan, the amino acid sequence of the peptide, and the site of glycan attachment. 24618751 8 42 theme collision 1787:1795 arg1 modulation 1804:1813 online collision energy modulation 1780:1813 online collision energy modulation 1780:1813 The practical usefulness of these observations was demonstrated through implementation of online collision energy modulation such that both glycan and peptide fragmentation were captured in the same spectrum, providing near-exhaustive glycopeptide characterization in a single experiment. 24618751 3 43 theme dissociation 669:680 arg1 use 644:646 use 644:646 use of collision-induced dissociation (CID) 644:686 This level of detail is often difficult to achieve using any single ion dissociation method; however, precedent does exist for use of collision-induced dissociation (CID) to establish either the connectivity of the oligosaccharide or the sequence of the polypeptide depending upon the applied collision energy. 24618751 2 44 theme monosaccharide 399:412 arg1 connectivity 414:425 the monosaccharide connectivity 395:425 the monosaccharide connectivity of the glycan 395:439 The aims of such experiments are often to determine the monosaccharide connectivity of the glycan, the amino acid sequence of the peptide, and the site of glycan attachment. 24618751 8 45 theme modulation 1804:1813 arg1 implementation 1762:1775 implementation 1762:1775 implementation of online collision energy modulation 1762:1813 The practical usefulness of these observations was demonstrated through implementation of online collision energy modulation such that both glycan and peptide fragmentation were captured in the same spectrum, providing near-exhaustive glycopeptide characterization in a single experiment. 24618751 1 46 theme analytical 258:267 arg1 approaches 269:278 the principal analytical approaches 244:278 the principal analytical approaches for assessing protein glycosylation in a site-specific manner 244:340 Tandem mass spectrometry (MS/MS) of glycopeptides stands among the principal analytical approaches for assessing protein glycosylation in a site-specific manner. 24618751 7 47 theme glycan 1599:1604 arg1 cleavage 1606:1613 glycan cleavage 1599:1613 glycan cleavage 1599:1613 Nevertheless, these data suggest that the energy requirements for peptide and glycan cleavage may be somewhat predictable based on characteristics of the precursor ion. 24618751 0 48 gly glycopeptides 74:86 arg2 glycopeptides 74:86 model N-linked glycopeptides 59:86 model N-linked glycopeptides 59:86 Energy-resolved collision-induced dissociation pathways of model N-linked glycopeptides: implications for capturing glycan connectivity and peptide sequence in a single experiment. 24618751 4 49 theme ions 1021:1024 arg1 characteristics 988:1002 specific physicochemical characteristics 963:1002 specific physicochemical characteristics of the precursor ions 963:1024 Unfortunately, the relative energy requirements for glycan and peptide cleavage have not been thoroughly characterized with respect to specific physicochemical characteristics of the precursor ions. 24618751 6 50 theme collision 1383:1391 arg1 energies 1393:1400 the absolute collision energies 1370:1400 the absolute collision energies at which either glycan or peptide fragmentations were accessed 1370:1463 While glycopeptide ions having disparate physical and chemical characteristics shared strikingly similar qualitative responses to increasing vibrational energy deposition, the absolute collision energies at which either glycan or peptide fragmentations were accessed varied substantially among the precursor ions examined. 24618751 1 51 theme protein 294:300 arg1 glycosylation 302:314 protein glycosylation 294:314 protein glycosylation 294:314 Tandem mass spectrometry (MS/MS) of glycopeptides stands among the principal analytical approaches for assessing protein glycosylation in a site-specific manner. 24618751 6 52 theme physical 1239:1246 arg1 characteristics 1261:1275 disparate physical and chemical characteristics 1229:1275 disparate physical and chemical characteristics 1229:1275 While glycopeptide ions having disparate physical and chemical characteristics shared strikingly similar qualitative responses to increasing vibrational energy deposition, the absolute collision energies at which either glycan or peptide fragmentations were accessed varied substantially among the precursor ions examined. 24618751 1 53 gly glycopeptides 217:229 arg2 glycopeptides 217:229 glycopeptides 217:229 glycopeptides 217:229 Tandem mass spectrometry (MS/MS) of glycopeptides stands among the principal analytical approaches for assessing protein glycosylation in a site-specific manner. 24618751 8 54 theme peptide 1841:1847 arg1 fragmentation 1849:1861 peptide fragmentation 1841:1861 peptide fragmentation 1841:1861 The practical usefulness of these observations was demonstrated through implementation of online collision energy modulation such that both glycan and peptide fragmentation were captured in the same spectrum, providing near-exhaustive glycopeptide characterization in a single experiment. 24618751 9 55 from capabilities 2048:2059 arg1 context 2075:2081 the context 2071:2081 the context of glycoproteomics 2071:2100 Overall, these results highlight the potential to further extend the capabilities of CID in the context of glycoproteomics. 24618751 6 56 gly glycopeptide 1204:1215 arg2 glycopeptide 1204:1215 glycopeptide ions 1204:1220 glycopeptide ions having disparate physical and chemical characteristics 1204:1275 While glycopeptide ions having disparate physical and chemical characteristics shared strikingly similar qualitative responses to increasing vibrational energy deposition, the absolute collision energies at which either glycan or peptide fragmentations were accessed varied substantially among the precursor ions examined. 24618751 8 57 gly glycopeptide 1925:1936 arg2 glycopeptide 1925:1936 near-exhaustive glycopeptide characterization 1909:1953 near-exhaustive glycopeptide characterization 1909:1953 The practical usefulness of these observations was demonstrated through implementation of online collision energy modulation such that both glycan and peptide fragmentation were captured in the same spectrum, providing near-exhaustive glycopeptide characterization in a single experiment. 24618751 6 58 theme vibrational 1339:1349 arg1 deposition 1358:1367 increasing vibrational energy deposition 1328:1367 increasing vibrational energy deposition 1328:1367 While glycopeptide ions having disparate physical and chemical characteristics shared strikingly similar qualitative responses to increasing vibrational energy deposition, the absolute collision energies at which either glycan or peptide fragmentations were accessed varied substantially among the precursor ions examined. 24618751 4 59 theme energy 856:861 arg1 requirements 863:874 the relative energy requirements 843:874 the relative energy requirements for glycan and peptide cleavage 843:906 Unfortunately, the relative energy requirements for glycan and peptide cleavage have not been thoroughly characterized with respect to specific physicochemical characteristics of the precursor ions. 24618751 6 60 theme glycopeptide 1204:1215 arg1 ions 1217:1220 glycopeptide ions 1204:1220 glycopeptide ions having disparate physical and chemical characteristics 1204:1275 While glycopeptide ions having disparate physical and chemical characteristics shared strikingly similar qualitative responses to increasing vibrational energy deposition, the absolute collision energies at which either glycan or peptide fragmentations were accessed varied substantially among the precursor ions examined. 24618751 9 61 theme glycoproteomics 2086:2100 arg1 context 2075:2081 the context 2071:2081 the context of glycoproteomics 2071:2100 Overall, these results highlight the potential to further extend the capabilities of CID in the context of glycoproteomics. 24618751 0 62 theme single 162:167 arg1 experiment 169:178 a single experiment 160:178 a single experiment 160:178 Energy-resolved collision-induced dissociation pathways of model N-linked glycopeptides: implications for capturing glycan connectivity and peptide sequence in a single experiment. 24618751 5 63 theme tryptic 1107:1113 arg1 glycopeptides 1115:1127 model tryptic glycopeptides 1101:1127 model tryptic glycopeptides derived from Erythrina cristagalli lectin and bovine ribonuclease B 1101:1195 This report describes case studies on the energy-resolved CID pathways of model tryptic glycopeptides derived from Erythrina cristagalli lectin and bovine ribonuclease B. 24618751 5 64 from studies 1054:1060 arg1 pathways 1089:1096 the energy-resolved CID pathways 1065:1096 the energy-resolved CID pathways of model tryptic glycopeptides derived from Erythrina cristagalli lectin and bovine ribonuclease B 1065:1195 This report describes case studies on the energy-resolved CID pathways of model tryptic glycopeptides derived from Erythrina cristagalli lectin and bovine ribonuclease B. 24618751 3 65 theme ion 585:587 arg1 method 602:607 any single ion dissociation method 574:607 any single ion dissociation method 574:607 This level of detail is often difficult to achieve using any single ion dissociation method; however, precedent does exist for use of collision-induced dissociation (CID) to establish either the connectivity of the oligosaccharide or the sequence of the polypeptide depending upon the applied collision energy. 24618751 6 66 theme similar 1295:1301 arg1 responses 1315:1323 strikingly similar qualitative responses 1284:1323 strikingly similar qualitative responses to increasing vibrational energy deposition 1284:1367 While glycopeptide ions having disparate physical and chemical characteristics shared strikingly similar qualitative responses to increasing vibrational energy deposition, the absolute collision energies at which either glycan or peptide fragmentations were accessed varied substantially among the precursor ions examined. 24618751 5 67 theme CID 1085:1087 arg1 pathways 1089:1096 the energy-resolved CID pathways 1065:1096 the energy-resolved CID pathways of model tryptic glycopeptides derived from Erythrina cristagalli lectin and bovine ribonuclease B 1065:1195 This report describes case studies on the energy-resolved CID pathways of model tryptic glycopeptides derived from Erythrina cristagalli lectin and bovine ribonuclease B. 24618751 8 68 theme near-exhaustive 1909:1923 arg1 characterization 1938:1953 near-exhaustive glycopeptide characterization 1909:1953 near-exhaustive glycopeptide characterization 1909:1953 The practical usefulness of these observations was demonstrated through implementation of online collision energy modulation such that both glycan and peptide fragmentation were captured in the same spectrum, providing near-exhaustive glycopeptide characterization in a single experiment. 24618751 3 69 theme collision 810:818 arg1 energy 820:825 the applied collision energy 798:825 the applied collision energy 798:825 This level of detail is often difficult to achieve using any single ion dissociation method; however, precedent does exist for use of collision-induced dissociation (CID) to establish either the connectivity of the oligosaccharide or the sequence of the polypeptide depending upon the applied collision energy. 24618751 2 70 theme attachment 505:514 arg1 sequence 457:464 the amino acid sequence 442:464 the amino acid sequence of the peptide 442:479 The aims of such experiments are often to determine the monosaccharide connectivity of the glycan, the amino acid sequence of the peptide, and the site of glycan attachment. 24618751 2 70 theme attachment 505:514 arg1 glycan 434:439 the glycan 430:439 the glycan 430:439 The aims of such experiments are often to determine the monosaccharide connectivity of the glycan, the amino acid sequence of the peptide, and the site of glycan attachment. 24618751 2 70 theme attachment 505:514 arg1 peptide 473:479 the peptide 469:479 the peptide 469:479 The aims of such experiments are often to determine the monosaccharide connectivity of the glycan, the amino acid sequence of the peptide, and the site of glycan attachment. 24618751 2 70 theme attachment 505:514 arg1 attachment 505:514 glycan attachment 498:514 glycan attachment 498:514 The aims of such experiments are often to determine the monosaccharide connectivity of the glycan, the amino acid sequence of the peptide, and the site of glycan attachment. 24618751 2 70 theme attachment 505:514 arg1 connectivity 414:425 the monosaccharide connectivity 395:425 the monosaccharide connectivity of the glycan 395:439 The aims of such experiments are often to determine the monosaccharide connectivity of the glycan, the amino acid sequence of the peptide, and the site of glycan attachment. 24618751 2 70 theme attachment 505:514 arg1 site 490:493 the site 486:493 the site of glycan attachment 486:514 The aims of such experiments are often to determine the monosaccharide connectivity of the glycan, the amino acid sequence of the peptide, and the site of glycan attachment. 24618751 6 71 theme chemical 1252:1259 arg1 characteristics 1261:1275 disparate physical and chemical characteristics 1229:1275 disparate physical and chemical characteristics 1229:1275 While glycopeptide ions having disparate physical and chemical characteristics shared strikingly similar qualitative responses to increasing vibrational energy deposition, the absolute collision energies at which either glycan or peptide fragmentations were accessed varied substantially among the precursor ions examined. 24618751 6 72 contain having 1222:1227 arg1 ions 1217:1220 glycopeptide ions 1204:1220 glycopeptide ions having disparate physical and chemical characteristics 1204:1275 While glycopeptide ions having disparate physical and chemical characteristics shared strikingly similar qualitative responses to increasing vibrational energy deposition, the absolute collision energies at which either glycan or peptide fragmentations were accessed varied substantially among the precursor ions examined. 24618751 6 72 contain having 1222:1227 arg2 characteristics 1261:1275 disparate physical and chemical characteristics 1229:1275 disparate physical and chemical characteristics 1229:1275 While glycopeptide ions having disparate physical and chemical characteristics shared strikingly similar qualitative responses to increasing vibrational energy deposition, the absolute collision energies at which either glycan or peptide fragmentations were accessed varied substantially among the precursor ions examined. 24618751 5 73 theme bovine 1175:1180 arg1 B 1195:1195 bovine ribonuclease B 1175:1195 bovine ribonuclease B 1175:1195 This report describes case studies on the energy-resolved CID pathways of model tryptic glycopeptides derived from Erythrina cristagalli lectin and bovine ribonuclease B. 24618751 1 74 theme Tandem 181:186 arg1 MS/MS 207:211 MS/MS 207:211 MS/MS 207:211 Tandem mass spectrometry (MS/MS) of glycopeptides stands among the principal analytical approaches for assessing protein glycosylation in a site-specific manner. 24618751 1 74 theme Tandem 181:186 arg1 spectrometry 193:204 Tandem mass spectrometry 181:204 Tandem mass spectrometry (MS/MS) of glycopeptides 181:229 Tandem mass spectrometry (MS/MS) of glycopeptides stands among the principal analytical approaches for assessing protein glycosylation in a site-specific manner. 24618751 7 75 theme ion 1685:1687 arg1 characteristics 1652:1666 characteristics 1652:1666 characteristics of the precursor ion 1652:1687 Nevertheless, these data suggest that the energy requirements for peptide and glycan cleavage may be somewhat predictable based on characteristics of the precursor ion. 24618751 4 76 theme precursor 1011:1019 arg1 ions 1021:1024 the precursor ions 1007:1024 the precursor ions 1007:1024 Unfortunately, the relative energy requirements for glycan and peptide cleavage have not been thoroughly characterized with respect to specific physicochemical characteristics of the precursor ions. 24618751 0 77 theme peptide 140:146 arg1 sequence 148:155 peptide sequence 140:155 peptide sequence 140:155 Energy-resolved collision-induced dissociation pathways of model N-linked glycopeptides: implications for capturing glycan connectivity and peptide sequence in a single experiment. 24618751 5 78 theme Erythrina 1142:1150 arg1 lectin 1164:1169 Erythrina cristagalli lectin 1142:1169 Erythrina cristagalli lectin 1142:1169 This report describes case studies on the energy-resolved CID pathways of model tryptic glycopeptides derived from Erythrina cristagalli lectin and bovine ribonuclease B. 24618751 4 79 theme physicochemical 972:986 arg1 characteristics 988:1002 specific physicochemical characteristics 963:1002 specific physicochemical characteristics of the precursor ions 963:1024 Unfortunately, the relative energy requirements for glycan and peptide cleavage have not been thoroughly characterized with respect to specific physicochemical characteristics of the precursor ions. 24618751 8 80 dep captured 1868:1875 arg1 such 1815:1818 such 1815:1818 such 1815:1818 The practical usefulness of these observations was demonstrated through implementation of online collision energy modulation such that both glycan and peptide fragmentation were captured in the same spectrum, providing near-exhaustive glycopeptide characterization in a single experiment. 24618751 0 81 theme collision-induced 16:32 arg1 pathways 47:54 Energy-resolved collision-induced dissociation pathways 0:54 Energy-resolved collision-induced dissociation pathways of model N-linked glycopeptides: implications for capturing glycan connectivity and peptide sequence in a single experiment. 0:179 Energy-resolved collision-induced dissociation pathways of model N-linked glycopeptides: implications for capturing glycan connectivity and peptide sequence in a single experiment. 24618751 5 82 attach derived 1129:1135 arg2 glycopeptides 1115:1127 model tryptic glycopeptides 1101:1127 model tryptic glycopeptides derived from Erythrina cristagalli lectin and bovine ribonuclease B 1101:1195 This report describes case studies on the energy-resolved CID pathways of model tryptic glycopeptides derived from Erythrina cristagalli lectin and bovine ribonuclease B. 24618751 5 82 attach derived 1129:1135 arg1 lectin 1164:1169 Erythrina cristagalli lectin 1142:1169 Erythrina cristagalli lectin 1142:1169 This report describes case studies on the energy-resolved CID pathways of model tryptic glycopeptides derived from Erythrina cristagalli lectin and bovine ribonuclease B. 24618751 5 82 attach derived 1129:1135 arg1 B 1195:1195 bovine ribonuclease B 1175:1195 bovine ribonuclease B 1175:1195 This report describes case studies on the energy-resolved CID pathways of model tryptic glycopeptides derived from Erythrina cristagalli lectin and bovine ribonuclease B. 24618751 8 83 theme same 1884:1887 arg1 spectrum 1889:1896 the same spectrum 1880:1896 the same spectrum 1880:1896 The practical usefulness of these observations was demonstrated through implementation of online collision energy modulation such that both glycan and peptide fragmentation were captured in the same spectrum, providing near-exhaustive glycopeptide characterization in a single experiment. 24618751 2 84 theme amino 446:450 arg1 sequence 457:464 the amino acid sequence 442:464 the amino acid sequence of the peptide 442:479 The aims of such experiments are often to determine the monosaccharide connectivity of the glycan, the amino acid sequence of the peptide, and the site of glycan attachment. 24618751 5 85 theme case 1049:1052 arg1 studies 1054:1060 case studies 1049:1060 case studies on the energy-resolved CID pathways of model tryptic glycopeptides derived from Erythrina cristagalli lectin and bovine ribonuclease B 1049:1195 This report describes case studies on the energy-resolved CID pathways of model tryptic glycopeptides derived from Erythrina cristagalli lectin and bovine ribonuclease B. 24618751 8 86 theme practical 1694:1702 arg1 usefulness 1704:1713 The practical usefulness 1690:1713 The practical usefulness of these observations 1690:1735 The practical usefulness of these observations was demonstrated through implementation of online collision energy modulation such that both glycan and peptide fragmentation were captured in the same spectrum, providing near-exhaustive glycopeptide characterization in a single experiment. 24618751 0 87 theme glycopeptides 74:86 arg1 pathways 47:54 Energy-resolved collision-induced dissociation pathways 0:54 Energy-resolved collision-induced dissociation pathways of model N-linked glycopeptides: implications for capturing glycan connectivity and peptide sequence in a single experiment. 0:179 Energy-resolved collision-induced dissociation pathways of model N-linked glycopeptides: implications for capturing glycan connectivity and peptide sequence in a single experiment. 24618751 8 88 theme energy 1797:1802 arg1 modulation 1804:1813 online collision energy modulation 1780:1813 online collision energy modulation 1780:1813 The practical usefulness of these observations was demonstrated through implementation of online collision energy modulation such that both glycan and peptide fragmentation were captured in the same spectrum, providing near-exhaustive glycopeptide characterization in a single experiment. 24618751 0 89 dep pathways 47:54 arg1 implications 89:100 implications 89:100 Energy-resolved collision-induced dissociation pathways of model N-linked glycopeptides: implications for capturing glycan connectivity and peptide sequence in a single experiment. 0:179 Energy-resolved collision-induced dissociation pathways of model N-linked glycopeptides: implications for capturing glycan connectivity and peptide sequence in a single experiment. 24618751 8 90 theme observations 1724:1735 arg1 usefulness 1704:1713 The practical usefulness 1690:1713 The practical usefulness of these observations 1690:1735 The practical usefulness of these observations was demonstrated through implementation of online collision energy modulation such that both glycan and peptide fragmentation were captured in the same spectrum, providing near-exhaustive glycopeptide characterization in a single experiment. 24618751 3 91 theme collision-induced 651:667 arg1 dissociation 669:680 collision-induced dissociation 651:680 collision-induced dissociation (CID) 651:686 This level of detail is often difficult to achieve using any single ion dissociation method; however, precedent does exist for use of collision-induced dissociation (CID) to establish either the connectivity of the oligosaccharide or the sequence of the polypeptide depending upon the applied collision energy. 24618751 3 91 theme collision-induced 651:667 arg1 CID 683:685 CID 683:685 CID 683:685 This level of detail is often difficult to achieve using any single ion dissociation method; however, precedent does exist for use of collision-induced dissociation (CID) to establish either the connectivity of the oligosaccharide or the sequence of the polypeptide depending upon the applied collision energy. 24618751 2 92 theme such 355:358 arg1 experiments 360:370 such experiments 355:370 such experiments 355:370 The aims of such experiments are often to determine the monosaccharide connectivity of the glycan, the amino acid sequence of the peptide, and the site of glycan attachment. 24618751 1 93 theme principal 248:256 arg1 approaches 269:278 the principal analytical approaches 244:278 the principal analytical approaches for assessing protein glycosylation in a site-specific manner 244:340 Tandem mass spectrometry (MS/MS) of glycopeptides stands among the principal analytical approaches for assessing protein glycosylation in a site-specific manner. 24618751 5 94 gly glycopeptides 1115:1127 arg2 glycopeptides 1115:1127 model tryptic glycopeptides 1101:1127 model tryptic glycopeptides derived from Erythrina cristagalli lectin and bovine ribonuclease B 1101:1195 This report describes case studies on the energy-resolved CID pathways of model tryptic glycopeptides derived from Erythrina cristagalli lectin and bovine ribonuclease B. 24618751 3 95 theme detail 531:536 arg1 level 522:526 This level 517:526 This level of detail 517:536 This level of detail is often difficult to achieve using any single ion dissociation method; however, precedent does exist for use of collision-induced dissociation (CID) to establish either the connectivity of the oligosaccharide or the sequence of the polypeptide depending upon the applied collision energy. 27927986 6 0 theme glucose 924:930 arg1 conditions 932:941 normal and high glucose conditions 908:941 normal and high glucose conditions 908:941 LPS-induced MAPK and IκB-α phosphorylation did not significantly differ at normal and high glucose conditions. 27927986 0 1 from Conditions 162:171 arg1 Cells 187:191 Macrophage Cells 176:191 Macrophage Cells 176:191 Lipopolysaccharide (LPS)-stimulated iNOS Induction Is Increased by Glucosamine under Normal Glucose Conditions but Is Inhibited by Glucosamine under High Glucose Conditions in Macrophage Cells. 27927986 10 2 theme glucose 1547:1553 arg1 conditions 1555:1564 high glucose conditions 1542:1564 high glucose conditions 1542:1564 The NF-κB inhibitor, pyrrolidine dithiocarbamate, inhibited LPS-induced iNOS expression under high glucose conditions but it did not influence iNOS induction under normal glucose conditions. 27927986 13 3 theme normal 2003:2008 arg1 excess 2019:2024 normal and fuel excess 2003:2024 normal and fuel excess 2003:2024 These results suggest that GlcN regulates inflammation by sensing energy states of normal and fuel excess. 27927986 12 4 theme actinomycin 1801:1811 arg1 D 1813:1813 actinomycin D 1801:1813 actinomycin D 1801:1813 By blocking transcription with actinomycin D, we found that stability of LPS-induced iNOS mRNA was increased by GlcN under normal glucose conditions. 27927986 7 5 theme significant 1111:1121 arg1 changes 1123:1129 no significant changes 1108:1129 no significant changes under normal glucose conditions 1108:1161 The activity of LPS-induced nuclear factor-κB (NF-κB) and DNA binding of c-Rel to the iNOS promoter were inhibited under high glucose conditions in comparison with no significant changes under normal glucose conditions. 27927986 13 6 theme fuel 2014:2017 arg1 excess 2019:2024 normal and fuel excess 2003:2024 normal and fuel excess 2003:2024 These results suggest that GlcN regulates inflammation by sensing energy states of normal and fuel excess. 27927986 9 7 theme high 1423:1426 arg1 conditions 1436:1445 high glucose conditions 1423:1445 high glucose conditions 1423:1445 However, both O-GlcNAcylation and DNA binding of c-Rel decreased under high glucose conditions. 27927986 11 8 theme NF-κB 1690:1694 arg1 binding 1700:1706 NF-κB DNA binding 1690:1706 NF-κB DNA binding 1690:1706 In addition, pyrrolidine dithiocarbamate inhibited NF-κB DNA binding and c-Rel O-GlcNAcylation only under high glucose conditions. 27927986 8 9 from increase 1207:1214 arg1 O-GlcNAcylation 1219:1233 O-GlcNAcylation 1219:1233 O-GlcNAcylation 1219:1233 In addition, we found that the LPS-induced increase in O-GlcNAcylation as well as DNA binding of c-Rel to the iNOS promoter were further increased by GlcN under normal glucose conditions. 27927986 4 10 theme mRNAs 660:664 arg1 up-regulation 620:632 LPS-induced up-regulation 608:632 LPS-induced up-regulation of COX-2, IL-6, and TNF-α mRNAs 608:664 Moreover, GlcN suppressed LPS-induced up-regulation of COX-2, IL-6, and TNF-α mRNAs under 25 mm glucose conditions yet did not inhibit up-regulation under 5 mm glucose conditions. 27927986 10 11 theme normal 1612:1617 arg1 conditions 1627:1636 normal glucose conditions 1612:1636 normal glucose conditions 1612:1636 The NF-κB inhibitor, pyrrolidine dithiocarbamate, inhibited LPS-induced iNOS expression under high glucose conditions but it did not influence iNOS induction under normal glucose conditions. 27927986 3 12 theme culture 562:568 arg1 conditions 570:579 high glucose culture conditions 549:579 high glucose culture conditions 549:579 However, GlcN suppressed NO/iNOS production under high glucose culture conditions. 27927986 8 13 theme LPS-induced 1195:1205 arg1 increase 1207:1214 the LPS-induced increase 1191:1214 the LPS-induced increase in O-GlcNAcylation as well as DNA binding of c-Rel to the iNOS promoter 1191:1286 In addition, we found that the LPS-induced increase in O-GlcNAcylation as well as DNA binding of c-Rel to the iNOS promoter were further increased by GlcN under normal glucose conditions. 27927986 8 14 theme c-Rel 1261:1265 arg1 binding 1250:1256 DNA binding 1246:1256 the LPS-induced increase in O-GlcNAcylation as well as DNA binding of c-Rel to the iNOS promoter 1191:1286 In addition, we found that the LPS-induced increase in O-GlcNAcylation as well as DNA binding of c-Rel to the iNOS promoter were further increased by GlcN under normal glucose conditions. 27927986 8 14 theme c-Rel 1261:1265 arg1 increase 1207:1214 the LPS-induced increase 1191:1214 the LPS-induced increase in O-GlcNAcylation as well as DNA binding of c-Rel to the iNOS promoter 1191:1286 In addition, we found that the LPS-induced increase in O-GlcNAcylation as well as DNA binding of c-Rel to the iNOS promoter were further increased by GlcN under normal glucose conditions. 27927986 7 15 theme glucose 1070:1076 arg1 conditions 1078:1087 high glucose conditions 1065:1087 high glucose conditions 1065:1087 The activity of LPS-induced nuclear factor-κB (NF-κB) and DNA binding of c-Rel to the iNOS promoter were inhibited under high glucose conditions in comparison with no significant changes under normal glucose conditions. 27927986 3 16 theme high 549:552 arg1 conditions 570:579 high glucose culture conditions 549:579 high glucose culture conditions 549:579 However, GlcN suppressed NO/iNOS production under high glucose culture conditions. 27927986 4 17 theme IL-6 644:647 arg1 up-regulation 620:632 LPS-induced up-regulation 608:632 LPS-induced up-regulation of COX-2, IL-6, and TNF-α mRNAs 608:664 Moreover, GlcN suppressed LPS-induced up-regulation of COX-2, IL-6, and TNF-α mRNAs under 25 mm glucose conditions yet did not inhibit up-regulation under 5 mm glucose conditions. 27927986 1 18 theme glucose 355:361 arg1 conditions 363:372 various glucose conditions 347:372 various glucose conditions 347:372 We investigated the regulatory effect of glucosamine (GlcN) for the production of nitric oxide (NO) and expression of inducible NO synthase (iNOS) under various glucose conditions in macrophage cells. 27927986 8 19 from binding 1250:1256 arg1 O-GlcNAcylation 1219:1233 O-GlcNAcylation 1219:1233 O-GlcNAcylation 1219:1233 In addition, we found that the LPS-induced increase in O-GlcNAcylation as well as DNA binding of c-Rel to the iNOS promoter were further increased by GlcN under normal glucose conditions. 27927986 1 20 theme regulatory 214:223 arg1 effect 225:230 the regulatory effect 210:230 the regulatory effect of glucosamine (GlcN) for the production of nitric oxide (NO) and expression of inducible NO synthase (iNOS) 210:339 We investigated the regulatory effect of glucosamine (GlcN) for the production of nitric oxide (NO) and expression of inducible NO synthase (iNOS) under various glucose conditions in macrophage cells. 27927986 7 21 theme binding 1006:1012 arg1 activity 948:955 The activity 944:955 The activity of LPS-induced nuclear factor-κB (NF-κB) and DNA binding of c-Rel to the iNOS promoter 944:1042 The activity of LPS-induced nuclear factor-κB (NF-κB) and DNA binding of c-Rel to the iNOS promoter were inhibited under high glucose conditions in comparison with no significant changes under normal glucose conditions. 27927986 7 22 theme iNOS 1030:1033 arg1 promoter 1035:1042 the iNOS promoter 1026:1042 the iNOS promoter 1026:1042 The activity of LPS-induced nuclear factor-κB (NF-κB) and DNA binding of c-Rel to the iNOS promoter were inhibited under high glucose conditions in comparison with no significant changes under normal glucose conditions. 27927986 4 23 theme 25 672:673 arg1 mm 675:676 mm 675:676 mm 675:676 Moreover, GlcN suppressed LPS-induced up-regulation of COX-2, IL-6, and TNF-α mRNAs under 25 mm glucose conditions yet did not inhibit up-regulation under 5 mm glucose conditions. 27927986 2 24 theme LPS-stimulated 461:474 arg1 production 476:485 LPS-stimulated production 461:485 LPS-stimulated production of NO/iNOS 461:496 At normal glucose concentrations, GlcN dose dependently increased LPS-stimulated production of NO/iNOS. 27927986 0 25 theme Glucose 154:160 arg1 Conditions 162:171 High Glucose Conditions 149:171 High Glucose Conditions in Macrophage Cells 149:191 Lipopolysaccharide (LPS)-stimulated iNOS Induction Is Increased by Glucosamine under Normal Glucose Conditions but Is Inhibited by Glucosamine under High Glucose Conditions in Macrophage Cells. 27927986 4 26 theme glucose 678:684 arg1 conditions 686:695 25 mm glucose conditions 672:695 25 mm glucose conditions 672:695 Moreover, GlcN suppressed LPS-induced up-regulation of COX-2, IL-6, and TNF-α mRNAs under 25 mm glucose conditions yet did not inhibit up-regulation under 5 mm glucose conditions. 27927986 1 27 theme inducible 312:320 arg1 iNOS 335:338 iNOS 335:338 iNOS 335:338 We investigated the regulatory effect of glucosamine (GlcN) for the production of nitric oxide (NO) and expression of inducible NO synthase (iNOS) under various glucose conditions in macrophage cells. 27927986 1 27 theme inducible 312:320 arg1 synthase 325:332 inducible NO synthase 312:332 inducible NO synthase (iNOS) 312:339 We investigated the regulatory effect of glucosamine (GlcN) for the production of nitric oxide (NO) and expression of inducible NO synthase (iNOS) under various glucose conditions in macrophage cells. 27927986 7 28 theme factor-κB 980:988 arg1 activity 948:955 The activity 944:955 The activity of LPS-induced nuclear factor-κB (NF-κB) and DNA binding of c-Rel to the iNOS promoter 944:1042 The activity of LPS-induced nuclear factor-κB (NF-κB) and DNA binding of c-Rel to the iNOS promoter were inhibited under high glucose conditions in comparison with no significant changes under normal glucose conditions. 27927986 8 29 theme glucose 1332:1338 arg1 conditions 1340:1349 normal glucose conditions 1325:1349 normal glucose conditions 1325:1349 In addition, we found that the LPS-induced increase in O-GlcNAcylation as well as DNA binding of c-Rel to the iNOS promoter were further increased by GlcN under normal glucose conditions. 27927986 0 30 theme Normal 85:90 arg1 Conditions 100:109 Normal Glucose Conditions 85:109 Normal Glucose Conditions 85:109 Lipopolysaccharide (LPS)-stimulated iNOS Induction Is Increased by Glucosamine under Normal Glucose Conditions but Is Inhibited by Glucosamine under High Glucose Conditions in Macrophage Cells. 27927986 1 31 theme synthase 325:332 arg1 production 262:271 the production 258:271 the production of nitric oxide (NO) 258:292 We investigated the regulatory effect of glucosamine (GlcN) for the production of nitric oxide (NO) and expression of inducible NO synthase (iNOS) under various glucose conditions in macrophage cells. 27927986 1 31 theme synthase 325:332 arg1 expression 298:307 expression 298:307 expression of inducible NO synthase (iNOS) 298:339 We investigated the regulatory effect of glucosamine (GlcN) for the production of nitric oxide (NO) and expression of inducible NO synthase (iNOS) under various glucose conditions in macrophage cells. 27927986 7 32 theme LPS-induced 960:970 arg1 NF-κB 991:995 NF-κB 991:995 NF-κB 991:995 The activity of LPS-induced nuclear factor-κB (NF-κB) and DNA binding of c-Rel to the iNOS promoter were inhibited under high glucose conditions in comparison with no significant changes under normal glucose conditions. 27927986 7 32 theme LPS-induced 960:970 arg1 factor-κB 980:988 LPS-induced nuclear factor-κB 960:988 LPS-induced nuclear factor-κB (NF-κB) 960:996 The activity of LPS-induced nuclear factor-κB (NF-κB) and DNA binding of c-Rel to the iNOS promoter were inhibited under high glucose conditions in comparison with no significant changes under normal glucose conditions. 27927986 10 33 theme pyrrolidine 1469:1479 arg1 inhibitor 1458:1466 The NF-κB inhibitor 1448:1466 The NF-κB inhibitor 1448:1466 The NF-κB inhibitor, pyrrolidine dithiocarbamate, inhibited LPS-induced iNOS expression under high glucose conditions but it did not influence iNOS induction under normal glucose conditions. 27927986 10 33 theme pyrrolidine 1469:1479 arg1 dithiocarbamate 1481:1495 pyrrolidine dithiocarbamate 1469:1495 pyrrolidine dithiocarbamate 1469:1495 The NF-κB inhibitor, pyrrolidine dithiocarbamate, inhibited LPS-induced iNOS expression under high glucose conditions but it did not influence iNOS induction under normal glucose conditions. 27927986 0 34 theme iNOS 36:39 arg1 Induction 41:49 Lipopolysaccharide (LPS)-stimulated iNOS Induction 0:49 Lipopolysaccharide (LPS)-stimulated iNOS Induction 0:49 Lipopolysaccharide (LPS)-stimulated iNOS Induction Is Increased by Glucosamine under Normal Glucose Conditions but Is Inhibited by Glucosamine under High Glucose Conditions in Macrophage Cells. 27927986 5 35 theme LPS-induced 804:814 arg1 expression 821:830 LPS-induced iNOS expression 804:830 LPS-induced iNOS expression 804:830 Glucose itself dose dependently increased LPS-induced iNOS expression. 27927986 2 36 theme normal 398:403 arg1 concentrations 413:426 normal glucose concentrations 398:426 normal glucose concentrations 398:426 At normal glucose concentrations, GlcN dose dependently increased LPS-stimulated production of NO/iNOS. 27927986 10 37 theme LPS-induced 1508:1518 arg1 expression 1525:1534 LPS-induced iNOS expression 1508:1534 LPS-induced iNOS expression 1508:1534 The NF-κB inhibitor, pyrrolidine dithiocarbamate, inhibited LPS-induced iNOS expression under high glucose conditions but it did not influence iNOS induction under normal glucose conditions. 27927986 4 38 theme 5 737:737 arg1 mm 739:740 mm 739:740 mm 739:740 Moreover, GlcN suppressed LPS-induced up-regulation of COX-2, IL-6, and TNF-α mRNAs under 25 mm glucose conditions yet did not inhibit up-regulation under 5 mm glucose conditions. 27927986 7 39 theme DNA 1002:1004 arg1 binding 1006:1012 DNA binding 1002:1012 DNA binding of c-Rel to the iNOS promoter 1002:1042 The activity of LPS-induced nuclear factor-κB (NF-κB) and DNA binding of c-Rel to the iNOS promoter were inhibited under high glucose conditions in comparison with no significant changes under normal glucose conditions. 27927986 1 40 theme nitric 276:281 arg1 NO 290:291 NO 290:291 NO 290:291 We investigated the regulatory effect of glucosamine (GlcN) for the production of nitric oxide (NO) and expression of inducible NO synthase (iNOS) under various glucose conditions in macrophage cells. 27927986 1 40 theme nitric 276:281 arg1 oxide 283:287 nitric oxide 276:287 nitric oxide (NO) 276:292 We investigated the regulatory effect of glucosamine (GlcN) for the production of nitric oxide (NO) and expression of inducible NO synthase (iNOS) under various glucose conditions in macrophage cells. 27927986 12 41 theme normal 1893:1898 arg1 conditions 1908:1917 normal glucose conditions 1893:1917 normal glucose conditions 1893:1917 By blocking transcription with actinomycin D, we found that stability of LPS-induced iNOS mRNA was increased by GlcN under normal glucose conditions. 27927986 0 42 theme -stimulated 24:34 arg1 Induction 41:49 Lipopolysaccharide (LPS)-stimulated iNOS Induction 0:49 Lipopolysaccharide (LPS)-stimulated iNOS Induction 0:49 Lipopolysaccharide (LPS)-stimulated iNOS Induction Is Increased by Glucosamine under Normal Glucose Conditions but Is Inhibited by Glucosamine under High Glucose Conditions in Macrophage Cells. 27927986 5 43 theme itself 770:775 arg1 dose 777:780 Glucose itself dose 762:780 Glucose itself dose 762:780 Glucose itself dose dependently increased LPS-induced iNOS expression. 27927986 12 44 theme iNOS 1855:1858 arg1 mRNA 1860:1863 LPS-induced iNOS mRNA 1843:1863 LPS-induced iNOS mRNA 1843:1863 By blocking transcription with actinomycin D, we found that stability of LPS-induced iNOS mRNA was increased by GlcN under normal glucose conditions. 27927986 2 45 theme GlcN 429:432 arg1 dose 434:437 GlcN dose 429:437 GlcN dose 429:437 At normal glucose concentrations, GlcN dose dependently increased LPS-stimulated production of NO/iNOS. 27927986 10 46 theme high 1542:1545 arg1 conditions 1555:1564 high glucose conditions 1542:1564 high glucose conditions 1542:1564 The NF-κB inhibitor, pyrrolidine dithiocarbamate, inhibited LPS-induced iNOS expression under high glucose conditions but it did not influence iNOS induction under normal glucose conditions. 27927986 7 47 theme glucose 1144:1150 arg1 conditions 1152:1161 normal glucose conditions 1137:1161 normal glucose conditions 1137:1161 The activity of LPS-induced nuclear factor-κB (NF-κB) and DNA binding of c-Rel to the iNOS promoter were inhibited under high glucose conditions in comparison with no significant changes under normal glucose conditions. 27927986 6 48 theme LPS-induced 833:843 arg1 phosphorylation 860:874 LPS-induced MAPK and IκB-α phosphorylation 833:874 LPS-induced MAPK and IκB-α phosphorylation 833:874 LPS-induced MAPK and IκB-α phosphorylation did not significantly differ at normal and high glucose conditions. 27927986 11 49 theme glucose 1750:1756 arg1 conditions 1758:1767 high glucose conditions 1745:1767 high glucose conditions 1745:1767 In addition, pyrrolidine dithiocarbamate inhibited NF-κB DNA binding and c-Rel O-GlcNAcylation only under high glucose conditions. 27927986 1 50 theme glucosamine 235:245 arg1 effect 225:230 the regulatory effect 210:230 the regulatory effect of glucosamine (GlcN) for the production of nitric oxide (NO) and expression of inducible NO synthase (iNOS) 210:339 We investigated the regulatory effect of glucosamine (GlcN) for the production of nitric oxide (NO) and expression of inducible NO synthase (iNOS) under various glucose conditions in macrophage cells. 27927986 4 51 theme LPS-induced 608:618 arg1 up-regulation 620:632 LPS-induced up-regulation 608:632 LPS-induced up-regulation of COX-2, IL-6, and TNF-α mRNAs 608:664 Moreover, GlcN suppressed LPS-induced up-regulation of COX-2, IL-6, and TNF-α mRNAs under 25 mm glucose conditions yet did not inhibit up-regulation under 5 mm glucose conditions. 27927986 0 52 theme Macrophage 176:185 arg1 Cells 187:191 Macrophage Cells 176:191 Macrophage Cells 176:191 Lipopolysaccharide (LPS)-stimulated iNOS Induction Is Increased by Glucosamine under Normal Glucose Conditions but Is Inhibited by Glucosamine under High Glucose Conditions in Macrophage Cells. 27927986 9 53 theme c-Rel 1401:1405 arg1 binding 1390:1396 DNA binding 1386:1396 DNA binding of c-Rel 1386:1405 However, both O-GlcNAcylation and DNA binding of c-Rel decreased under high glucose conditions. 27927986 9 53 theme c-Rel 1401:1405 arg1 O-GlcNAcylation 1366:1380 O-GlcNAcylation 1366:1380 O-GlcNAcylation 1366:1380 However, both O-GlcNAcylation and DNA binding of c-Rel decreased under high glucose conditions. 27927986 6 54 theme high 919:922 arg1 conditions 932:941 normal and high glucose conditions 908:941 normal and high glucose conditions 908:941 LPS-induced MAPK and IκB-α phosphorylation did not significantly differ at normal and high glucose conditions. 27927986 10 55 theme iNOS 1591:1594 arg1 induction 1596:1604 iNOS induction 1591:1604 iNOS induction 1591:1604 The NF-κB inhibitor, pyrrolidine dithiocarbamate, inhibited LPS-induced iNOS expression under high glucose conditions but it did not influence iNOS induction under normal glucose conditions. 27927986 11 56 theme pyrrolidine 1652:1662 arg1 dithiocarbamate 1664:1678 pyrrolidine dithiocarbamate 1652:1678 pyrrolidine dithiocarbamate 1652:1678 In addition, pyrrolidine dithiocarbamate inhibited NF-κB DNA binding and c-Rel O-GlcNAcylation only under high glucose conditions. 27927986 3 57 theme NO/iNOS 524:530 arg1 production 532:541 NO/iNOS production 524:541 NO/iNOS production 524:541 However, GlcN suppressed NO/iNOS production under high glucose culture conditions. 27927986 6 58 theme normal 908:913 arg1 conditions 932:941 normal and high glucose conditions 908:941 normal and high glucose conditions 908:941 LPS-induced MAPK and IκB-α phosphorylation did not significantly differ at normal and high glucose conditions. 27927986 13 59 theme excess 2019:2024 arg1 states 1993:1998 energy states 1986:1998 energy states of normal and fuel excess 1986:2024 These results suggest that GlcN regulates inflammation by sensing energy states of normal and fuel excess. 27927986 9 60 theme glucose 1428:1434 arg1 conditions 1436:1445 high glucose conditions 1423:1445 high glucose conditions 1423:1445 However, both O-GlcNAcylation and DNA binding of c-Rel decreased under high glucose conditions. 27927986 10 61 theme glucose 1619:1625 arg1 conditions 1627:1636 normal glucose conditions 1612:1636 normal glucose conditions 1612:1636 The NF-κB inhibitor, pyrrolidine dithiocarbamate, inhibited LPS-induced iNOS expression under high glucose conditions but it did not influence iNOS induction under normal glucose conditions. 27927986 11 62 theme DNA 1696:1698 arg1 binding 1700:1706 NF-κB DNA binding 1690:1706 NF-κB DNA binding 1690:1706 In addition, pyrrolidine dithiocarbamate inhibited NF-κB DNA binding and c-Rel O-GlcNAcylation only under high glucose conditions. 27927986 13 63 theme energy 1986:1991 arg1 states 1993:1998 energy states 1986:1998 energy states of normal and fuel excess 1986:2024 These results suggest that GlcN regulates inflammation by sensing energy states of normal and fuel excess. 27927986 3 64 theme glucose 554:560 arg1 conditions 570:579 high glucose culture conditions 549:579 high glucose culture conditions 549:579 However, GlcN suppressed NO/iNOS production under high glucose culture conditions. 27927986 4 65 theme TNF-α 654:658 arg1 mRNAs 660:664 TNF-α mRNAs 654:664 TNF-α mRNAs 654:664 Moreover, GlcN suppressed LPS-induced up-regulation of COX-2, IL-6, and TNF-α mRNAs under 25 mm glucose conditions yet did not inhibit up-regulation under 5 mm glucose conditions. 27927986 7 66 theme high 1065:1068 arg1 conditions 1078:1087 high glucose conditions 1065:1087 high glucose conditions 1065:1087 The activity of LPS-induced nuclear factor-κB (NF-κB) and DNA binding of c-Rel to the iNOS promoter were inhibited under high glucose conditions in comparison with no significant changes under normal glucose conditions. 27927986 1 67 theme various 347:353 arg1 conditions 363:372 various glucose conditions 347:372 various glucose conditions 347:372 We investigated the regulatory effect of glucosamine (GlcN) for the production of nitric oxide (NO) and expression of inducible NO synthase (iNOS) under various glucose conditions in macrophage cells. 27927986 8 68 theme DNA 1246:1248 arg1 binding 1250:1256 DNA binding 1246:1256 the LPS-induced increase in O-GlcNAcylation as well as DNA binding of c-Rel to the iNOS promoter 1191:1286 In addition, we found that the LPS-induced increase in O-GlcNAcylation as well as DNA binding of c-Rel to the iNOS promoter were further increased by GlcN under normal glucose conditions. 27927986 0 69 theme High 149:152 arg1 Conditions 162:171 High Glucose Conditions 149:171 High Glucose Conditions in Macrophage Cells 149:191 Lipopolysaccharide (LPS)-stimulated iNOS Induction Is Increased by Glucosamine under Normal Glucose Conditions but Is Inhibited by Glucosamine under High Glucose Conditions in Macrophage Cells. 27927986 8 70 theme iNOS 1274:1277 arg1 promoter 1279:1286 the iNOS promoter 1270:1286 the iNOS promoter 1270:1286 In addition, we found that the LPS-induced increase in O-GlcNAcylation as well as DNA binding of c-Rel to the iNOS promoter were further increased by GlcN under normal glucose conditions. 27927986 1 71 theme macrophage 377:386 arg1 cells 388:392 macrophage cells 377:392 macrophage cells 377:392 We investigated the regulatory effect of glucosamine (GlcN) for the production of nitric oxide (NO) and expression of inducible NO synthase (iNOS) under various glucose conditions in macrophage cells. 27927986 4 72 theme glucose 742:748 arg1 conditions 750:759 5 mm glucose conditions 737:759 5 mm glucose conditions 737:759 Moreover, GlcN suppressed LPS-induced up-regulation of COX-2, IL-6, and TNF-α mRNAs under 25 mm glucose conditions yet did not inhibit up-regulation under 5 mm glucose conditions. 27927986 4 73 theme COX-2 637:641 arg1 up-regulation 620:632 LPS-induced up-regulation 608:632 LPS-induced up-regulation of COX-2, IL-6, and TNF-α mRNAs 608:664 Moreover, GlcN suppressed LPS-induced up-regulation of COX-2, IL-6, and TNF-α mRNAs under 25 mm glucose conditions yet did not inhibit up-regulation under 5 mm glucose conditions. 27927986 4 74 theme mm 675:676 arg1 conditions 686:695 25 mm glucose conditions 672:695 25 mm glucose conditions 672:695 Moreover, GlcN suppressed LPS-induced up-regulation of COX-2, IL-6, and TNF-α mRNAs under 25 mm glucose conditions yet did not inhibit up-regulation under 5 mm glucose conditions. 27927986 0 75 theme Glucose 92:98 arg1 Conditions 100:109 Normal Glucose Conditions 85:109 Normal Glucose Conditions 85:109 Lipopolysaccharide (LPS)-stimulated iNOS Induction Is Increased by Glucosamine under Normal Glucose Conditions but Is Inhibited by Glucosamine under High Glucose Conditions in Macrophage Cells. 27927986 1 76 theme NO 322:323 arg1 iNOS 335:338 iNOS 335:338 iNOS 335:338 We investigated the regulatory effect of glucosamine (GlcN) for the production of nitric oxide (NO) and expression of inducible NO synthase (iNOS) under various glucose conditions in macrophage cells. 27927986 1 76 theme NO 322:323 arg1 synthase 325:332 inducible NO synthase 312:332 inducible NO synthase (iNOS) 312:339 We investigated the regulatory effect of glucosamine (GlcN) for the production of nitric oxide (NO) and expression of inducible NO synthase (iNOS) under various glucose conditions in macrophage cells. 27927986 8 77 theme normal 1325:1330 arg1 conditions 1340:1349 normal glucose conditions 1325:1349 normal glucose conditions 1325:1349 In addition, we found that the LPS-induced increase in O-GlcNAcylation as well as DNA binding of c-Rel to the iNOS promoter were further increased by GlcN under normal glucose conditions. 27927986 4 78 theme mm 739:740 arg1 conditions 750:759 5 mm glucose conditions 737:759 5 mm glucose conditions 737:759 Moreover, GlcN suppressed LPS-induced up-regulation of COX-2, IL-6, and TNF-α mRNAs under 25 mm glucose conditions yet did not inhibit up-regulation under 5 mm glucose conditions. 27927986 7 79 theme nuclear 972:978 arg1 NF-κB 991:995 NF-κB 991:995 NF-κB 991:995 The activity of LPS-induced nuclear factor-κB (NF-κB) and DNA binding of c-Rel to the iNOS promoter were inhibited under high glucose conditions in comparison with no significant changes under normal glucose conditions. 27927986 7 79 theme nuclear 972:978 arg1 factor-κB 980:988 LPS-induced nuclear factor-κB 960:988 LPS-induced nuclear factor-κB (NF-κB) 960:996 The activity of LPS-induced nuclear factor-κB (NF-κB) and DNA binding of c-Rel to the iNOS promoter were inhibited under high glucose conditions in comparison with no significant changes under normal glucose conditions. 27927986 2 80 theme NO/iNOS 490:496 arg1 production 476:485 LPS-stimulated production 461:485 LPS-stimulated production of NO/iNOS 461:496 At normal glucose concentrations, GlcN dose dependently increased LPS-stimulated production of NO/iNOS. 27927986 2 81 theme glucose 405:411 arg1 concentrations 413:426 normal glucose concentrations 398:426 normal glucose concentrations 398:426 At normal glucose concentrations, GlcN dose dependently increased LPS-stimulated production of NO/iNOS. 27927986 10 82 theme NF-κB 1452:1456 arg1 inhibitor 1458:1466 The NF-κB inhibitor 1448:1466 The NF-κB inhibitor 1448:1466 The NF-κB inhibitor, pyrrolidine dithiocarbamate, inhibited LPS-induced iNOS expression under high glucose conditions but it did not influence iNOS induction under normal glucose conditions. 27927986 10 82 theme NF-κB 1452:1456 arg1 dithiocarbamate 1481:1495 pyrrolidine dithiocarbamate 1469:1495 pyrrolidine dithiocarbamate 1469:1495 The NF-κB inhibitor, pyrrolidine dithiocarbamate, inhibited LPS-induced iNOS expression under high glucose conditions but it did not influence iNOS induction under normal glucose conditions. 27927986 5 83 theme iNOS 816:819 arg1 expression 821:830 LPS-induced iNOS expression 804:830 LPS-induced iNOS expression 804:830 Glucose itself dose dependently increased LPS-induced iNOS expression. 27927986 12 84 theme glucose 1900:1906 arg1 conditions 1908:1917 normal glucose conditions 1893:1917 normal glucose conditions 1893:1917 By blocking transcription with actinomycin D, we found that stability of LPS-induced iNOS mRNA was increased by GlcN under normal glucose conditions. 27927986 5 85 theme Glucose 762:768 arg1 dose 777:780 Glucose itself dose 762:780 Glucose itself dose 762:780 Glucose itself dose dependently increased LPS-induced iNOS expression. 27927986 1 86 theme oxide 283:287 arg1 production 262:271 the production 258:271 the production of nitric oxide (NO) 258:292 We investigated the regulatory effect of glucosamine (GlcN) for the production of nitric oxide (NO) and expression of inducible NO synthase (iNOS) under various glucose conditions in macrophage cells. 27927986 1 86 theme oxide 283:287 arg1 expression 298:307 expression 298:307 expression of inducible NO synthase (iNOS) 298:339 We investigated the regulatory effect of glucosamine (GlcN) for the production of nitric oxide (NO) and expression of inducible NO synthase (iNOS) under various glucose conditions in macrophage cells. 27927986 11 87 theme c-Rel 1712:1716 arg1 O-GlcNAcylation 1718:1732 c-Rel O-GlcNAcylation 1712:1732 c-Rel O-GlcNAcylation 1712:1732 In addition, pyrrolidine dithiocarbamate inhibited NF-κB DNA binding and c-Rel O-GlcNAcylation only under high glucose conditions. 27927986 7 88 theme normal 1137:1142 arg1 conditions 1152:1161 normal glucose conditions 1137:1161 normal glucose conditions 1137:1161 The activity of LPS-induced nuclear factor-κB (NF-κB) and DNA binding of c-Rel to the iNOS promoter were inhibited under high glucose conditions in comparison with no significant changes under normal glucose conditions. 27927986 6 89 theme IκB-α 854:858 arg1 phosphorylation 860:874 LPS-induced MAPK and IκB-α phosphorylation 833:874 LPS-induced MAPK and IκB-α phosphorylation 833:874 LPS-induced MAPK and IκB-α phosphorylation did not significantly differ at normal and high glucose conditions. 27927986 12 90 theme LPS-induced 1843:1853 arg1 mRNA 1860:1863 LPS-induced iNOS mRNA 1843:1863 LPS-induced iNOS mRNA 1843:1863 By blocking transcription with actinomycin D, we found that stability of LPS-induced iNOS mRNA was increased by GlcN under normal glucose conditions. 27927986 6 91 theme MAPK 845:848 arg1 phosphorylation 860:874 LPS-induced MAPK and IκB-α phosphorylation 833:874 LPS-induced MAPK and IκB-α phosphorylation 833:874 LPS-induced MAPK and IκB-α phosphorylation did not significantly differ at normal and high glucose conditions. 27927986 12 92 theme mRNA 1860:1863 arg1 stability 1830:1838 stability 1830:1838 stability of LPS-induced iNOS mRNA 1830:1863 By blocking transcription with actinomycin D, we found that stability of LPS-induced iNOS mRNA was increased by GlcN under normal glucose conditions. 27927986 7 93 with comparison 1092:1101 arg1 changes 1123:1129 no significant changes 1108:1129 no significant changes under normal glucose conditions 1108:1161 The activity of LPS-induced nuclear factor-κB (NF-κB) and DNA binding of c-Rel to the iNOS promoter were inhibited under high glucose conditions in comparison with no significant changes under normal glucose conditions. 27927986 10 94 theme iNOS 1520:1523 arg1 expression 1525:1534 LPS-induced iNOS expression 1508:1534 LPS-induced iNOS expression 1508:1534 The NF-κB inhibitor, pyrrolidine dithiocarbamate, inhibited LPS-induced iNOS expression under high glucose conditions but it did not influence iNOS induction under normal glucose conditions. 27927986 11 95 theme high 1745:1748 arg1 conditions 1758:1767 high glucose conditions 1745:1767 high glucose conditions 1745:1767 In addition, pyrrolidine dithiocarbamate inhibited NF-κB DNA binding and c-Rel O-GlcNAcylation only under high glucose conditions. 27927986 7 96 theme c-Rel 1017:1021 arg1 NF-κB 991:995 NF-κB 991:995 NF-κB 991:995 The activity of LPS-induced nuclear factor-κB (NF-κB) and DNA binding of c-Rel to the iNOS promoter were inhibited under high glucose conditions in comparison with no significant changes under normal glucose conditions. 27927986 7 96 theme c-Rel 1017:1021 arg1 factor-κB 980:988 LPS-induced nuclear factor-κB 960:988 LPS-induced nuclear factor-κB (NF-κB) 960:996 The activity of LPS-induced nuclear factor-κB (NF-κB) and DNA binding of c-Rel to the iNOS promoter were inhibited under high glucose conditions in comparison with no significant changes under normal glucose conditions. 27927986 7 96 theme c-Rel 1017:1021 arg1 binding 1006:1012 DNA binding 1002:1012 DNA binding of c-Rel to the iNOS promoter 1002:1042 The activity of LPS-induced nuclear factor-κB (NF-κB) and DNA binding of c-Rel to the iNOS promoter were inhibited under high glucose conditions in comparison with no significant changes under normal glucose conditions. 27927986 9 97 theme DNA 1386:1388 arg1 binding 1390:1396 DNA binding 1386:1396 DNA binding of c-Rel 1386:1405 However, both O-GlcNAcylation and DNA binding of c-Rel decreased under high glucose conditions. 28584052 0 0 theme intellectual 82:93 arg1 disability 95:104 X-linked intellectual disability 73:104 X-linked intellectual disability 73:104 Mutations in N-acetylglucosamine (O-GlcNAc) transferase in patients with X-linked intellectual disability. 28584052 10 1 theme substrates 1623:1632 arg1 array 1600:1604 a complex array 1590:1604 a complex array of glycosylation substrates 1590:1632 Recombinant OGT bearing the p.Arg284Pro mutation was prone to unfolding and exhibited reduced glycosylation activity against a complex array of glycosylation substrates and proteolytic processing of the transcription factor host cell factor 1, which is also encoded by an XLID-associated gene. 28584052 9 2 theme patient-derived 1436:1450 arg1 fibroblasts 1452:1462 the corresponding patient-derived fibroblasts 1418:1462 the corresponding patient-derived fibroblasts 1418:1462 We also found that the c.463-6T>G mutation leads to aberrant mRNA splicing, but no stable truncated protein was detected in the corresponding patient-derived fibroblasts. 28584052 7 3 link patient-derived 1090:1104 arg1 fibroblasts 1106:1116 both patient-derived fibroblasts 1085:1116 both patient-derived fibroblasts 1085:1116 We observed slightly reduced levels of OGT protein and reduced levels of its opposing enzyme O-GlcNAcase in both patient-derived fibroblasts, but global O-GlcNAc levels appeared to be unaffected. 28584052 7 4 theme enzyme 1063:1068 arg1 O-GlcNAcase 1070:1080 its opposing enzyme O-GlcNAcase 1050:1080 its opposing enzyme O-GlcNAcase 1050:1080 We observed slightly reduced levels of OGT protein and reduced levels of its opposing enzyme O-GlcNAcase in both patient-derived fibroblasts, but global O-GlcNAc levels appeared to be unaffected. 28584052 11 5 theme factor 1822:1827 arg1 proteolysis 1831:1841 host cell factor 1 proteolysis 1812:1841 host cell factor 1 proteolysis 1812:1841 We conclude that defects in O-GlcNAc homeostasis and host cell factor 1 proteolysis may play roles in mediation of XLID in individuals with OGT mutations. 28584052 0 6 theme X-linked 73:80 arg1 disability 95:104 X-linked intellectual disability 73:104 X-linked intellectual disability 73:104 Mutations in N-acetylglucosamine (O-GlcNAc) transferase in patients with X-linked intellectual disability. 28584052 11 7 with individuals 1882:1892 arg1 mutations 1903:1911 OGT mutations 1899:1911 OGT mutations 1899:1911 We conclude that defects in O-GlcNAc homeostasis and host cell factor 1 proteolysis may play roles in mediation of XLID in individuals with OGT mutations. 28584052 1 8 theme protein 166:172 arg1 O-GlcNAcylation 174:188 protein O-GlcNAcylation 166:188 protein O-GlcNAcylation 166:188 N-Acetylglucosamine (O-GlcNAc) transferase (OGT) regulates protein O-GlcNAcylation, an essential and dynamic post-translational modification. 28584052 1 8 theme protein 166:172 arg1 modification 235:246 an essential and dynamic post-translational modification 191:246 an essential and dynamic post-translational modification 191:246 N-Acetylglucosamine (O-GlcNAc) transferase (OGT) regulates protein O-GlcNAcylation, an essential and dynamic post-translational modification. 28584052 10 9 theme transcription 1668:1680 arg1 factor 1699:1704 the transcription factor host cell factor 1 1664:1706 the transcription factor host cell factor 1 1664:1706 Recombinant OGT bearing the p.Arg284Pro mutation was prone to unfolding and exhibited reduced glycosylation activity against a complex array of glycosylation substrates and proteolytic processing of the transcription factor host cell factor 1, which is also encoded by an XLID-associated gene. 28584052 0 10 from Mutations 0:8 arg1 N-acetylglucosamine 13:31 N-acetylglucosamine 13:31 N-acetylglucosamine (O-GlcNAc) 13:42 Mutations in N-acetylglucosamine (O-GlcNAc) transferase in patients with X-linked intellectual disability. 28584052 0 10 from Mutations 0:8 arg1 O-GlcNAc 34:41 O-GlcNAc 34:41 O-GlcNAc 34:41 Mutations in N-acetylglucosamine (O-GlcNAc) transferase in patients with X-linked intellectual disability. 28584052 4 11 from mutations 559:567 arg1 gene 580:583 the OGT gene 572:583 the OGT gene 572:583 However, mutations in the OGT gene have not yet been functionally confirmed in humans. 28584052 7 12 theme reduced 998:1004 arg1 levels 1006:1011 slightly reduced levels 989:1011 slightly reduced levels of OGT protein 989:1026 We observed slightly reduced levels of OGT protein and reduced levels of its opposing enzyme O-GlcNAcase in both patient-derived fibroblasts, but global O-GlcNAc levels appeared to be unaffected. 28584052 9 13 theme aberrant 1346:1353 arg1 splicing 1360:1367 aberrant mRNA splicing 1346:1367 aberrant mRNA splicing 1346:1367 We also found that the c.463-6T>G mutation leads to aberrant mRNA splicing, but no stable truncated protein was detected in the corresponding patient-derived fibroblasts. 28584052 9 14 located detected 1406:1413 arg1 fibroblasts 1452:1462 the corresponding patient-derived fibroblasts 1418:1462 the corresponding patient-derived fibroblasts 1418:1462 We also found that the c.463-6T>G mutation leads to aberrant mRNA splicing, but no stable truncated protein was detected in the corresponding patient-derived fibroblasts. 28584052 9 14 located detected 1406:1413 arg2 protein 1394:1400 no stable truncated protein 1374:1400 no stable truncated protein 1374:1400 We also found that the c.463-6T>G mutation leads to aberrant mRNA splicing, but no stable truncated protein was detected in the corresponding patient-derived fibroblasts. 28584052 9 15 theme mRNA 1355:1358 arg1 splicing 1360:1367 aberrant mRNA splicing 1346:1367 aberrant mRNA splicing 1346:1367 We also found that the c.463-6T>G mutation leads to aberrant mRNA splicing, but no stable truncated protein was detected in the corresponding patient-derived fibroblasts. 28584052 0 16 link X-linked 73:80 arg1 disability 95:104 X-linked intellectual disability 73:104 X-linked intellectual disability 73:104 Mutations in N-acetylglucosamine (O-GlcNAc) transferase in patients with X-linked intellectual disability. 28584052 2 17 theme cytosolic 310:318 arg1 proteins 320:327 numerous nuclear and cytosolic proteins 289:327 numerous nuclear and cytosolic proteins 289:327 The O-GlcNAc modification is present on numerous nuclear and cytosolic proteins and has been implicated in essential cellular functions such as signaling and gene expression. 28584052 11 18 from defects 1776:1782 arg1 homeostasis 1796:1806 O-GlcNAc homeostasis 1787:1806 O-GlcNAc homeostasis 1787:1806 We conclude that defects in O-GlcNAc homeostasis and host cell factor 1 proteolysis may play roles in mediation of XLID in individuals with OGT mutations. 28584052 11 18 from defects 1776:1782 arg1 proteolysis 1831:1841 host cell factor 1 proteolysis 1812:1841 host cell factor 1 proteolysis 1812:1841 We conclude that defects in O-GlcNAc homeostasis and host cell factor 1 proteolysis may play roles in mediation of XLID in individuals with OGT mutations. 28584052 0 19 from transferase 44:54 arg1 patients 59:66 patients 59:66 patients with X-linked intellectual disability 59:104 Mutations in N-acetylglucosamine (O-GlcNAc) transferase in patients with X-linked intellectual disability. 28584052 7 20 theme global 1123:1128 arg1 levels 1139:1144 global O-GlcNAc levels 1123:1144 global O-GlcNAc levels 1123:1144 We observed slightly reduced levels of OGT protein and reduced levels of its opposing enzyme O-GlcNAcase in both patient-derived fibroblasts, but global O-GlcNAc levels appeared to be unaffected. 28584052 0 21 with patients 59:66 arg1 disability 95:104 X-linked intellectual disability 73:104 X-linked intellectual disability 73:104 Mutations in N-acetylglucosamine (O-GlcNAc) transferase in patients with X-linked intellectual disability. 28584052 5 22 theme missense 777:784 arg1 mutations 671:679 two hemizygous mutations 656:679 two hemizygous mutations in OGT in individuals with X-linked intellectual disability (XLID) and dysmorphic features: one missense mutation (p.Arg284Pro) and one mutation leading to a splicing defect (c.463-6T>G) 656:866 Here, we report on two hemizygous mutations in OGT in individuals with X-linked intellectual disability (XLID) and dysmorphic features: one missense mutation (p.Arg284Pro) and one mutation leading to a splicing defect (c.463-6T>G). 28584052 5 22 theme missense 777:784 arg1 p.Arg284Pro 796:806 p.Arg284Pro 796:806 p.Arg284Pro 796:806 Here, we report on two hemizygous mutations in OGT in individuals with X-linked intellectual disability (XLID) and dysmorphic features: one missense mutation (p.Arg284Pro) and one mutation leading to a splicing defect (c.463-6T>G). 28584052 5 22 theme missense 777:784 arg1 mutation 786:793 one missense mutation 773:793 one missense mutation (p.Arg284Pro) 773:807 Here, we report on two hemizygous mutations in OGT in individuals with X-linked intellectual disability (XLID) and dysmorphic features: one missense mutation (p.Arg284Pro) and one mutation leading to a splicing defect (c.463-6T>G). 28584052 6 23 theme tetratricopeptide 898:914 arg1 repeats 916:922 the tetratricopeptide repeats 894:922 the tetratricopeptide repeats of OGT that are essential for substrate recognition 894:974 Both mutations reside in the tetratricopeptide repeats of OGT that are essential for substrate recognition. 28584052 5 24 theme hemizygous 660:669 arg1 mutations 671:679 two hemizygous mutations 656:679 two hemizygous mutations in OGT in individuals with X-linked intellectual disability (XLID) and dysmorphic features: one missense mutation (p.Arg284Pro) and one mutation leading to a splicing defect (c.463-6T>G) 656:866 Here, we report on two hemizygous mutations in OGT in individuals with X-linked intellectual disability (XLID) and dysmorphic features: one missense mutation (p.Arg284Pro) and one mutation leading to a splicing defect (c.463-6T>G). 28584052 5 24 theme hemizygous 660:669 arg1 mutation 817:824 one mutation 813:824 one mutation leading to a splicing defect (c.463-6T>G) 813:866 Here, we report on two hemizygous mutations in OGT in individuals with X-linked intellectual disability (XLID) and dysmorphic features: one missense mutation (p.Arg284Pro) and one mutation leading to a splicing defect (c.463-6T>G). 28584052 5 24 theme hemizygous 660:669 arg1 mutation 786:793 one missense mutation 773:793 one missense mutation (p.Arg284Pro) 773:807 Here, we report on two hemizygous mutations in OGT in individuals with X-linked intellectual disability (XLID) and dysmorphic features: one missense mutation (p.Arg284Pro) and one mutation leading to a splicing defect (c.463-6T>G). 28584052 10 25 theme reduced 1551:1557 arg1 activity 1573:1580 reduced glycosylation activity 1551:1580 reduced glycosylation activity against a complex array of glycosylation substrates 1551:1632 Recombinant OGT bearing the p.Arg284Pro mutation was prone to unfolding and exhibited reduced glycosylation activity against a complex array of glycosylation substrates and proteolytic processing of the transcription factor host cell factor 1, which is also encoded by an XLID-associated gene. 28584052 2 26 theme nuclear 298:304 arg1 proteins 320:327 numerous nuclear and cytosolic proteins 289:327 numerous nuclear and cytosolic proteins 289:327 The O-GlcNAc modification is present on numerous nuclear and cytosolic proteins and has been implicated in essential cellular functions such as signaling and gene expression. 28584052 10 27 theme factor 1699:1704 arg1 activity 1573:1580 reduced glycosylation activity 1551:1580 reduced glycosylation activity against a complex array of glycosylation substrates 1551:1632 Recombinant OGT bearing the p.Arg284Pro mutation was prone to unfolding and exhibited reduced glycosylation activity against a complex array of glycosylation substrates and proteolytic processing of the transcription factor host cell factor 1, which is also encoded by an XLID-associated gene. 28584052 10 27 theme factor 1699:1704 arg1 processing 1650:1659 proteolytic processing 1638:1659 proteolytic processing of the transcription factor host cell factor 1, which is also encoded by an XLID-associated gene 1638:1756 Recombinant OGT bearing the p.Arg284Pro mutation was prone to unfolding and exhibited reduced glycosylation activity against a complex array of glycosylation substrates and proteolytic processing of the transcription factor host cell factor 1, which is also encoded by an XLID-associated gene. 28584052 10 28 theme glycosylation 1609:1621 arg1 substrates 1623:1632 glycosylation substrates 1609:1632 glycosylation substrates 1609:1632 Recombinant OGT bearing the p.Arg284Pro mutation was prone to unfolding and exhibited reduced glycosylation activity against a complex array of glycosylation substrates and proteolytic processing of the transcription factor host cell factor 1, which is also encoded by an XLID-associated gene. 28584052 10 29 theme p.Arg284Pro 1493:1503 arg1 mutation 1505:1512 the p.Arg284Pro mutation 1489:1512 the p.Arg284Pro mutation 1489:1512 Recombinant OGT bearing the p.Arg284Pro mutation was prone to unfolding and exhibited reduced glycosylation activity against a complex array of glycosylation substrates and proteolytic processing of the transcription factor host cell factor 1, which is also encoded by an XLID-associated gene. 28584052 7 30 theme O-GlcNAcase 1070:1080 arg1 levels 1006:1011 slightly reduced levels 989:1011 slightly reduced levels of OGT protein 989:1026 We observed slightly reduced levels of OGT protein and reduced levels of its opposing enzyme O-GlcNAcase in both patient-derived fibroblasts, but global O-GlcNAc levels appeared to be unaffected. 28584052 7 30 theme O-GlcNAcase 1070:1080 arg1 levels 1040:1045 reduced levels 1032:1045 reduced levels of its opposing enzyme O-GlcNAcase 1032:1080 We observed slightly reduced levels of OGT protein and reduced levels of its opposing enzyme O-GlcNAcase in both patient-derived fibroblasts, but global O-GlcNAc levels appeared to be unaffected. 28584052 3 31 theme protein 455:461 arg1 O-GlcNAcylation 463:477 protein O-GlcNAcylation 455:477 protein O-GlcNAcylation 455:477 Accordingly, altered levels of protein O-GlcNAcylation have been associated with developmental defects and neurodegeneration. 28584052 10 32 theme cell 1694:1697 arg1 factor 1699:1704 the transcription factor host cell factor 1 1664:1706 the transcription factor host cell factor 1 1664:1706 Recombinant OGT bearing the p.Arg284Pro mutation was prone to unfolding and exhibited reduced glycosylation activity against a complex array of glycosylation substrates and proteolytic processing of the transcription factor host cell factor 1, which is also encoded by an XLID-associated gene. 28584052 5 33 from mutations 671:679 arg1 individuals 691:701 individuals 691:701 individuals with X-linked intellectual disability (XLID) and dysmorphic features 691:770 Here, we report on two hemizygous mutations in OGT in individuals with X-linked intellectual disability (XLID) and dysmorphic features: one missense mutation (p.Arg284Pro) and one mutation leading to a splicing defect (c.463-6T>G). 28584052 5 33 from mutations 671:679 arg1 OGT 684:686 OGT 684:686 OGT 684:686 Here, we report on two hemizygous mutations in OGT in individuals with X-linked intellectual disability (XLID) and dysmorphic features: one missense mutation (p.Arg284Pro) and one mutation leading to a splicing defect (c.463-6T>G). 28584052 11 34 theme cell 1817:1820 arg1 factor 1822:1827 host cell factor 1 1812:1829 host cell factor 1 proteolysis 1812:1841 We conclude that defects in O-GlcNAc homeostasis and host cell factor 1 proteolysis may play roles in mediation of XLID in individuals with OGT mutations. 28584052 3 35 theme O-GlcNAcylation 463:477 arg1 levels 445:450 altered levels 437:450 altered levels of protein O-GlcNAcylation 437:477 Accordingly, altered levels of protein O-GlcNAcylation have been associated with developmental defects and neurodegeneration. 28584052 5 36 theme splicing 839:846 arg1 c.463-6T>G 856:865 c.463-6T>G 856:865 c.463-6T>G 856:865 Here, we report on two hemizygous mutations in OGT in individuals with X-linked intellectual disability (XLID) and dysmorphic features: one missense mutation (p.Arg284Pro) and one mutation leading to a splicing defect (c.463-6T>G). 28584052 5 36 theme splicing 839:846 arg1 defect 848:853 a splicing defect 837:853 a splicing defect (c.463-6T>G) 837:866 Here, we report on two hemizygous mutations in OGT in individuals with X-linked intellectual disability (XLID) and dysmorphic features: one missense mutation (p.Arg284Pro) and one mutation leading to a splicing defect (c.463-6T>G). 28584052 9 37 theme stable 1377:1382 arg1 protein 1394:1400 no stable truncated protein 1374:1400 no stable truncated protein 1374:1400 We also found that the c.463-6T>G mutation leads to aberrant mRNA splicing, but no stable truncated protein was detected in the corresponding patient-derived fibroblasts. 28584052 7 38 theme patient-derived 1090:1104 arg1 fibroblasts 1106:1116 both patient-derived fibroblasts 1085:1116 both patient-derived fibroblasts 1085:1116 We observed slightly reduced levels of OGT protein and reduced levels of its opposing enzyme O-GlcNAcase in both patient-derived fibroblasts, but global O-GlcNAc levels appeared to be unaffected. 28584052 8 39 theme global 1228:1233 arg1 O-GlcNAcylation 1235:1249 global O-GlcNAcylation 1228:1249 global O-GlcNAcylation 1228:1249 Our data suggest that mutant cells attempt to maintain global O-GlcNAcylation by down-regulating O-GlcNAcase expression. 28584052 1 40 theme N-Acetylglucosamine 107:125 arg1 transferase 138:148 N-Acetylglucosamine (O-GlcNAc) transferase 107:148 N-Acetylglucosamine (O-GlcNAc) transferase (OGT) 107:154 N-Acetylglucosamine (O-GlcNAc) transferase (OGT) regulates protein O-GlcNAcylation, an essential and dynamic post-translational modification. 28584052 1 40 theme N-Acetylglucosamine 107:125 arg1 OGT 151:153 OGT 151:153 OGT 151:153 N-Acetylglucosamine (O-GlcNAc) transferase (OGT) regulates protein O-GlcNAcylation, an essential and dynamic post-translational modification. 28584052 3 41 theme developmental 505:517 arg1 defects 519:525 developmental defects 505:525 developmental defects 505:525 Accordingly, altered levels of protein O-GlcNAcylation have been associated with developmental defects and neurodegeneration. 28584052 10 42 theme factor 1682:1687 arg1 factor 1699:1704 the transcription factor host cell factor 1 1664:1706 the transcription factor host cell factor 1 1664:1706 Recombinant OGT bearing the p.Arg284Pro mutation was prone to unfolding and exhibited reduced glycosylation activity against a complex array of glycosylation substrates and proteolytic processing of the transcription factor host cell factor 1, which is also encoded by an XLID-associated gene. 28584052 9 43 theme truncated 1384:1392 arg1 protein 1394:1400 no stable truncated protein 1374:1400 no stable truncated protein 1374:1400 We also found that the c.463-6T>G mutation leads to aberrant mRNA splicing, but no stable truncated protein was detected in the corresponding patient-derived fibroblasts. 28584052 11 44 theme XLID 1874:1877 arg1 mediation 1861:1869 mediation 1861:1869 mediation of XLID 1861:1877 We conclude that defects in O-GlcNAc homeostasis and host cell factor 1 proteolysis may play roles in mediation of XLID in individuals with OGT mutations. 28584052 1 45 theme dynamic 208:214 arg1 O-GlcNAcylation 174:188 protein O-GlcNAcylation 166:188 protein O-GlcNAcylation 166:188 N-Acetylglucosamine (O-GlcNAc) transferase (OGT) regulates protein O-GlcNAcylation, an essential and dynamic post-translational modification. 28584052 1 45 theme dynamic 208:214 arg1 modification 235:246 an essential and dynamic post-translational modification 191:246 an essential and dynamic post-translational modification 191:246 N-Acetylglucosamine (O-GlcNAc) transferase (OGT) regulates protein O-GlcNAcylation, an essential and dynamic post-translational modification. 28584052 5 46 dep mutations 671:679 arg1 mutation 817:824 one mutation 813:824 one mutation leading to a splicing defect (c.463-6T>G) 813:866 Here, we report on two hemizygous mutations in OGT in individuals with X-linked intellectual disability (XLID) and dysmorphic features: one missense mutation (p.Arg284Pro) and one mutation leading to a splicing defect (c.463-6T>G). 28584052 5 46 dep mutations 671:679 arg1 mutations 671:679 two hemizygous mutations 656:679 two hemizygous mutations in OGT in individuals with X-linked intellectual disability (XLID) and dysmorphic features: one missense mutation (p.Arg284Pro) and one mutation leading to a splicing defect (c.463-6T>G) 656:866 Here, we report on two hemizygous mutations in OGT in individuals with X-linked intellectual disability (XLID) and dysmorphic features: one missense mutation (p.Arg284Pro) and one mutation leading to a splicing defect (c.463-6T>G). 28584052 5 46 dep mutations 671:679 arg1 p.Arg284Pro 796:806 p.Arg284Pro 796:806 p.Arg284Pro 796:806 Here, we report on two hemizygous mutations in OGT in individuals with X-linked intellectual disability (XLID) and dysmorphic features: one missense mutation (p.Arg284Pro) and one mutation leading to a splicing defect (c.463-6T>G). 28584052 5 46 dep mutations 671:679 arg1 mutation 786:793 one missense mutation 773:793 one missense mutation (p.Arg284Pro) 773:807 Here, we report on two hemizygous mutations in OGT in individuals with X-linked intellectual disability (XLID) and dysmorphic features: one missense mutation (p.Arg284Pro) and one mutation leading to a splicing defect (c.463-6T>G). 28584052 10 47 theme glycosylation 1559:1571 arg1 activity 1573:1580 reduced glycosylation activity 1551:1580 reduced glycosylation activity against a complex array of glycosylation substrates 1551:1632 Recombinant OGT bearing the p.Arg284Pro mutation was prone to unfolding and exhibited reduced glycosylation activity against a complex array of glycosylation substrates and proteolytic processing of the transcription factor host cell factor 1, which is also encoded by an XLID-associated gene. 28584052 10 48 theme XLID-associated 1737:1751 arg1 gene 1753:1756 an XLID-associated gene 1734:1756 an XLID-associated gene 1734:1756 Recombinant OGT bearing the p.Arg284Pro mutation was prone to unfolding and exhibited reduced glycosylation activity against a complex array of glycosylation substrates and proteolytic processing of the transcription factor host cell factor 1, which is also encoded by an XLID-associated gene. 28584052 2 49 theme gene 407:410 arg1 expression 412:421 gene expression 407:421 gene expression 407:421 The O-GlcNAc modification is present on numerous nuclear and cytosolic proteins and has been implicated in essential cellular functions such as signaling and gene expression. 28584052 1 50 theme post-translational 216:233 arg1 O-GlcNAcylation 174:188 protein O-GlcNAcylation 166:188 protein O-GlcNAcylation 166:188 N-Acetylglucosamine (O-GlcNAc) transferase (OGT) regulates protein O-GlcNAcylation, an essential and dynamic post-translational modification. 28584052 1 50 theme post-translational 216:233 arg1 modification 235:246 an essential and dynamic post-translational modification 191:246 an essential and dynamic post-translational modification 191:246 N-Acetylglucosamine (O-GlcNAc) transferase (OGT) regulates protein O-GlcNAcylation, an essential and dynamic post-translational modification. 28584052 11 51 theme OGT 1899:1901 arg1 mutations 1903:1911 OGT mutations 1899:1911 OGT mutations 1899:1911 We conclude that defects in O-GlcNAc homeostasis and host cell factor 1 proteolysis may play roles in mediation of XLID in individuals with OGT mutations. 28584052 5 52 theme dysmorphic 752:761 arg1 features 763:770 dysmorphic features 752:770 dysmorphic features 752:770 Here, we report on two hemizygous mutations in OGT in individuals with X-linked intellectual disability (XLID) and dysmorphic features: one missense mutation (p.Arg284Pro) and one mutation leading to a splicing defect (c.463-6T>G). 28584052 2 53 theme O-GlcNAc 253:260 arg1 present 278:284 present 278:284 present 278:284 The O-GlcNAc modification is present on numerous nuclear and cytosolic proteins and has been implicated in essential cellular functions such as signaling and gene expression. 28584052 2 53 theme O-GlcNAc 253:260 arg1 modification 262:273 The O-GlcNAc modification 249:273 The O-GlcNAc modification 249:273 The O-GlcNAc modification is present on numerous nuclear and cytosolic proteins and has been implicated in essential cellular functions such as signaling and gene expression. 28584052 8 54 theme mutant 1195:1200 arg1 cells 1202:1206 mutant cells 1195:1206 mutant cells 1195:1206 Our data suggest that mutant cells attempt to maintain global O-GlcNAcylation by down-regulating O-GlcNAcase expression. 28584052 8 55 theme O-GlcNAcase 1270:1280 arg1 expression 1282:1291 O-GlcNAcase expression 1270:1291 O-GlcNAcase expression 1270:1291 Our data suggest that mutant cells attempt to maintain global O-GlcNAcylation by down-regulating O-GlcNAcase expression. 28584052 4 56 theme OGT 576:578 arg1 gene 580:583 the OGT gene 572:583 the OGT gene 572:583 However, mutations in the OGT gene have not yet been functionally confirmed in humans. 28584052 5 57 theme X-linked 708:715 arg1 disability 730:739 X-linked intellectual disability 708:739 X-linked intellectual disability (XLID) 708:746 Here, we report on two hemizygous mutations in OGT in individuals with X-linked intellectual disability (XLID) and dysmorphic features: one missense mutation (p.Arg284Pro) and one mutation leading to a splicing defect (c.463-6T>G). 28584052 5 57 theme X-linked 708:715 arg1 XLID 742:745 XLID 742:745 XLID 742:745 Here, we report on two hemizygous mutations in OGT in individuals with X-linked intellectual disability (XLID) and dysmorphic features: one missense mutation (p.Arg284Pro) and one mutation leading to a splicing defect (c.463-6T>G). 28584052 1 58 theme essential 194:202 arg1 O-GlcNAcylation 174:188 protein O-GlcNAcylation 166:188 protein O-GlcNAcylation 166:188 N-Acetylglucosamine (O-GlcNAc) transferase (OGT) regulates protein O-GlcNAcylation, an essential and dynamic post-translational modification. 28584052 1 58 theme essential 194:202 arg1 modification 235:246 an essential and dynamic post-translational modification 191:246 an essential and dynamic post-translational modification 191:246 N-Acetylglucosamine (O-GlcNAc) transferase (OGT) regulates protein O-GlcNAcylation, an essential and dynamic post-translational modification. 28584052 3 59 theme altered 437:443 arg1 levels 445:450 altered levels 437:450 altered levels of protein O-GlcNAcylation 437:477 Accordingly, altered levels of protein O-GlcNAcylation have been associated with developmental defects and neurodegeneration. 28584052 6 60 theme substrate 954:962 arg1 recognition 964:974 substrate recognition 954:974 substrate recognition 954:974 Both mutations reside in the tetratricopeptide repeats of OGT that are essential for substrate recognition. 28584052 5 61 theme intellectual 717:728 arg1 disability 730:739 X-linked intellectual disability 708:739 X-linked intellectual disability (XLID) 708:746 Here, we report on two hemizygous mutations in OGT in individuals with X-linked intellectual disability (XLID) and dysmorphic features: one missense mutation (p.Arg284Pro) and one mutation leading to a splicing defect (c.463-6T>G). 28584052 5 61 theme intellectual 717:728 arg1 XLID 742:745 XLID 742:745 XLID 742:745 Here, we report on two hemizygous mutations in OGT in individuals with X-linked intellectual disability (XLID) and dysmorphic features: one missense mutation (p.Arg284Pro) and one mutation leading to a splicing defect (c.463-6T>G). 28584052 7 62 theme O-GlcNAc 1130:1137 arg1 levels 1139:1144 global O-GlcNAc levels 1123:1144 global O-GlcNAc levels 1123:1144 We observed slightly reduced levels of OGT protein and reduced levels of its opposing enzyme O-GlcNAcase in both patient-derived fibroblasts, but global O-GlcNAc levels appeared to be unaffected. 28584052 2 63 theme cellular 366:373 arg1 functions 375:383 essential cellular functions 356:383 essential cellular functions such as signaling and gene expression 356:421 The O-GlcNAc modification is present on numerous nuclear and cytosolic proteins and has been implicated in essential cellular functions such as signaling and gene expression. 28584052 2 63 theme cellular 366:373 arg1 signaling 393:401 signaling 393:401 signaling 393:401 The O-GlcNAc modification is present on numerous nuclear and cytosolic proteins and has been implicated in essential cellular functions such as signaling and gene expression. 28584052 2 63 theme cellular 366:373 arg1 expression 412:421 gene expression 407:421 gene expression 407:421 The O-GlcNAc modification is present on numerous nuclear and cytosolic proteins and has been implicated in essential cellular functions such as signaling and gene expression. 28584052 9 64 link patient-derived 1436:1450 arg1 fibroblasts 1452:1462 the corresponding patient-derived fibroblasts 1418:1462 the corresponding patient-derived fibroblasts 1418:1462 We also found that the c.463-6T>G mutation leads to aberrant mRNA splicing, but no stable truncated protein was detected in the corresponding patient-derived fibroblasts. 28584052 10 65 theme complex 1592:1598 arg1 array 1600:1604 a complex array 1590:1604 a complex array of glycosylation substrates 1590:1632 Recombinant OGT bearing the p.Arg284Pro mutation was prone to unfolding and exhibited reduced glycosylation activity against a complex array of glycosylation substrates and proteolytic processing of the transcription factor host cell factor 1, which is also encoded by an XLID-associated gene. 28584052 11 66 theme host 1812:1815 arg1 factor 1822:1827 host cell factor 1 1812:1829 host cell factor 1 proteolysis 1812:1841 We conclude that defects in O-GlcNAc homeostasis and host cell factor 1 proteolysis may play roles in mediation of XLID in individuals with OGT mutations. 28584052 2 67 theme numerous 289:296 arg1 proteins 320:327 numerous nuclear and cytosolic proteins 289:327 numerous nuclear and cytosolic proteins 289:327 The O-GlcNAc modification is present on numerous nuclear and cytosolic proteins and has been implicated in essential cellular functions such as signaling and gene expression. 28584052 7 68 theme reduced 1032:1038 arg1 levels 1040:1045 reduced levels 1032:1045 reduced levels of its opposing enzyme O-GlcNAcase 1032:1080 We observed slightly reduced levels of OGT protein and reduced levels of its opposing enzyme O-GlcNAcase in both patient-derived fibroblasts, but global O-GlcNAc levels appeared to be unaffected. 28584052 2 69 theme essential 356:364 arg1 functions 375:383 essential cellular functions 356:383 essential cellular functions such as signaling and gene expression 356:421 The O-GlcNAc modification is present on numerous nuclear and cytosolic proteins and has been implicated in essential cellular functions such as signaling and gene expression. 28584052 2 69 theme essential 356:364 arg1 signaling 393:401 signaling 393:401 signaling 393:401 The O-GlcNAc modification is present on numerous nuclear and cytosolic proteins and has been implicated in essential cellular functions such as signaling and gene expression. 28584052 2 69 theme essential 356:364 arg1 expression 412:421 gene expression 407:421 gene expression 407:421 The O-GlcNAc modification is present on numerous nuclear and cytosolic proteins and has been implicated in essential cellular functions such as signaling and gene expression. 28584052 9 70 theme corresponding 1422:1434 arg1 fibroblasts 1452:1462 the corresponding patient-derived fibroblasts 1418:1462 the corresponding patient-derived fibroblasts 1418:1462 We also found that the c.463-6T>G mutation leads to aberrant mRNA splicing, but no stable truncated protein was detected in the corresponding patient-derived fibroblasts. 28584052 7 71 theme opposing 1054:1061 arg1 O-GlcNAcase 1070:1080 its opposing enzyme O-GlcNAcase 1050:1080 its opposing enzyme O-GlcNAcase 1050:1080 We observed slightly reduced levels of OGT protein and reduced levels of its opposing enzyme O-GlcNAcase in both patient-derived fibroblasts, but global O-GlcNAc levels appeared to be unaffected. 28584052 11 72 theme O-GlcNAc 1787:1794 arg1 homeostasis 1796:1806 O-GlcNAc homeostasis 1787:1806 O-GlcNAc homeostasis 1787:1806 We conclude that defects in O-GlcNAc homeostasis and host cell factor 1 proteolysis may play roles in mediation of XLID in individuals with OGT mutations. 28584052 7 73 theme OGT 1016:1018 arg1 protein 1020:1026 OGT protein 1016:1026 OGT protein 1016:1026 We observed slightly reduced levels of OGT protein and reduced levels of its opposing enzyme O-GlcNAcase in both patient-derived fibroblasts, but global O-GlcNAc levels appeared to be unaffected. 28584052 5 74 link X-linked 708:715 arg1 disability 730:739 X-linked intellectual disability 708:739 X-linked intellectual disability (XLID) 708:746 Here, we report on two hemizygous mutations in OGT in individuals with X-linked intellectual disability (XLID) and dysmorphic features: one missense mutation (p.Arg284Pro) and one mutation leading to a splicing defect (c.463-6T>G). 28584052 5 74 link X-linked 708:715 arg1 XLID 742:745 XLID 742:745 XLID 742:745 Here, we report on two hemizygous mutations in OGT in individuals with X-linked intellectual disability (XLID) and dysmorphic features: one missense mutation (p.Arg284Pro) and one mutation leading to a splicing defect (c.463-6T>G). 28584052 10 75 theme proteolytic 1638:1648 arg1 processing 1650:1659 proteolytic processing 1638:1659 proteolytic processing of the transcription factor host cell factor 1, which is also encoded by an XLID-associated gene 1638:1756 Recombinant OGT bearing the p.Arg284Pro mutation was prone to unfolding and exhibited reduced glycosylation activity against a complex array of glycosylation substrates and proteolytic processing of the transcription factor host cell factor 1, which is also encoded by an XLID-associated gene. 28584052 9 76 theme c.463-6T>G 1317:1326 arg1 mutation 1328:1335 the c.463-6T>G mutation 1313:1335 the c.463-6T>G mutation 1313:1335 We also found that the c.463-6T>G mutation leads to aberrant mRNA splicing, but no stable truncated protein was detected in the corresponding patient-derived fibroblasts. 28584052 10 77 theme host 1689:1692 arg1 factor 1699:1704 the transcription factor host cell factor 1 1664:1706 the transcription factor host cell factor 1 1664:1706 Recombinant OGT bearing the p.Arg284Pro mutation was prone to unfolding and exhibited reduced glycosylation activity against a complex array of glycosylation substrates and proteolytic processing of the transcription factor host cell factor 1, which is also encoded by an XLID-associated gene. 28584052 7 78 theme protein 1020:1026 arg1 levels 1006:1011 slightly reduced levels 989:1011 slightly reduced levels of OGT protein 989:1026 We observed slightly reduced levels of OGT protein and reduced levels of its opposing enzyme O-GlcNAcase in both patient-derived fibroblasts, but global O-GlcNAc levels appeared to be unaffected. 28584052 7 78 theme protein 1020:1026 arg1 levels 1040:1045 reduced levels 1032:1045 reduced levels of its opposing enzyme O-GlcNAcase 1032:1080 We observed slightly reduced levels of OGT protein and reduced levels of its opposing enzyme O-GlcNAcase in both patient-derived fibroblasts, but global O-GlcNAc levels appeared to be unaffected. 28584052 5 79 with individuals 691:701 arg1 disability 730:739 X-linked intellectual disability 708:739 X-linked intellectual disability (XLID) 708:746 Here, we report on two hemizygous mutations in OGT in individuals with X-linked intellectual disability (XLID) and dysmorphic features: one missense mutation (p.Arg284Pro) and one mutation leading to a splicing defect (c.463-6T>G). 28584052 5 79 with individuals 691:701 arg1 features 763:770 dysmorphic features 752:770 dysmorphic features 752:770 Here, we report on two hemizygous mutations in OGT in individuals with X-linked intellectual disability (XLID) and dysmorphic features: one missense mutation (p.Arg284Pro) and one mutation leading to a splicing defect (c.463-6T>G). 28584052 5 79 with individuals 691:701 arg1 XLID 742:745 XLID 742:745 XLID 742:745 Here, we report on two hemizygous mutations in OGT in individuals with X-linked intellectual disability (XLID) and dysmorphic features: one missense mutation (p.Arg284Pro) and one mutation leading to a splicing defect (c.463-6T>G). 28584052 6 80 theme OGT 927:929 arg1 repeats 916:922 the tetratricopeptide repeats 894:922 the tetratricopeptide repeats of OGT that are essential for substrate recognition 894:974 Both mutations reside in the tetratricopeptide repeats of OGT that are essential for substrate recognition. 28584052 10 81 theme Recombinant 1465:1475 arg1 OGT 1477:1479 Recombinant OGT 1465:1479 Recombinant OGT bearing the p.Arg284Pro mutation 1465:1512 Recombinant OGT bearing the p.Arg284Pro mutation was prone to unfolding and exhibited reduced glycosylation activity against a complex array of glycosylation substrates and proteolytic processing of the transcription factor host cell factor 1, which is also encoded by an XLID-associated gene. 28584052 2 82 attach present 278:284 arg2 present 278:284 present 278:284 present 278:284 The O-GlcNAc modification is present on numerous nuclear and cytosolic proteins and has been implicated in essential cellular functions such as signaling and gene expression. 28584052 2 82 attach present 278:284 arg1 proteins 320:327 numerous nuclear and cytosolic proteins 289:327 numerous nuclear and cytosolic proteins 289:327 The O-GlcNAc modification is present on numerous nuclear and cytosolic proteins and has been implicated in essential cellular functions such as signaling and gene expression. 28584052 2 82 attach present 278:284 arg2 modification 262:273 The O-GlcNAc modification 249:273 The O-GlcNAc modification 249:273 The O-GlcNAc modification is present on numerous nuclear and cytosolic proteins and has been implicated in essential cellular functions such as signaling and gene expression. 28584052 2 83 located present 278:284 arg2 present 278:284 present 278:284 present 278:284 The O-GlcNAc modification is present on numerous nuclear and cytosolic proteins and has been implicated in essential cellular functions such as signaling and gene expression. 28584052 2 83 located present 278:284 arg1 proteins 320:327 numerous nuclear and cytosolic proteins 289:327 numerous nuclear and cytosolic proteins 289:327 The O-GlcNAc modification is present on numerous nuclear and cytosolic proteins and has been implicated in essential cellular functions such as signaling and gene expression. 28584052 2 83 located present 278:284 arg2 modification 262:273 The O-GlcNAc modification 249:273 The O-GlcNAc modification 249:273 The O-GlcNAc modification is present on numerous nuclear and cytosolic proteins and has been implicated in essential cellular functions such as signaling and gene expression. 29279740 2 0 from extent 341:346 arg1 discs 440:444 human degenerated intervertebral discs 407:444 human degenerated intervertebral discs 407:444 PURPOSE This study aimed to quantify the extent of O-GlcNAcylation and its associated enzymes (OGT/OGA) in human degenerated intervertebral discs. 29279740 3 1 theme such 568:571 arg1 modifications 592:604 such post-translational modifications 568:604 such post-translational modifications 568:604 OVERVIEW OF LITERATURE The O-GlcNAcylation of nuclear, cytoplasmic, and mitochondrial proteins as well as the effects of such post-translational modifications are currently the focus of extensive research. 29279740 5 2 theme chondrocyte 903:913 arg1 apoptosis 915:923 chondrocyte apoptosis 903:923 chondrocyte apoptosis 903:923 Mature intervertebral disc cells are chondrocyte-like cells, and O-GlcNAc has been shown to promote chondrocyte apoptosis in vitro. 29279740 8 3 used used 1182:1185 arg2 slices 1157:1162 Tissue slices 1150:1162 Tissue slices (4-µm-thick) 1150:1175 Tissue slices (4-µm-thick) were used for hematoxylin-eosin staining and immunohistochemistry. 29279740 8 3 used used 1182:1185 arg2 4-µm-thick 1165:1174 4-µm-thick 1165:1174 4-µm-thick 1165:1174 Tissue slices (4-µm-thick) were used for hematoxylin-eosin staining and immunohistochemistry. 29279740 4 4 theme chronic 714:720 arg1 illnesses 722:730 chronic illnesses 714:730 chronic illnesses 714:730 O-GlcNAcylation is believed to contribute to the etiology of chronic illnesses by acting as a nutrient and stress sensor in the cellular environment. 29279740 12 5 theme disc 1691:1694 arg1 degeneration 1701:1712 intervertebral disc cell degeneration 1676:1712 intervertebral disc cell degeneration 1676:1712 CONCLUSIONS O-GlcNAc and OGA/OGT expression is shown to correlate for the first time with intervertebral disc cell degeneration. 29279740 3 6 theme modifications 592:604 arg1 OVERVIEW 447:454 OVERVIEW 447:454 OVERVIEW OF LITERATURE The O-GlcNAcylation of nuclear, cytoplasmic, and mitochondrial proteins as well as the effects of such post-translational modifications 447:604 OVERVIEW OF LITERATURE The O-GlcNAcylation of nuclear, cytoplasmic, and mitochondrial proteins as well as the effects of such post-translational modifications are currently the focus of extensive research. 29279740 3 6 theme modifications 592:604 arg1 effects 557:563 the effects 553:563 OVERVIEW OF LITERATURE The O-GlcNAcylation of nuclear, cytoplasmic, and mitochondrial proteins as well as the effects of such post-translational modifications 447:604 OVERVIEW OF LITERATURE The O-GlcNAcylation of nuclear, cytoplasmic, and mitochondrial proteins as well as the effects of such post-translational modifications are currently the focus of extensive research. 29279740 3 6 theme modifications 592:604 arg1 focus 624:628 the focus 620:628 the focus of extensive research 620:650 OVERVIEW OF LITERATURE The O-GlcNAcylation of nuclear, cytoplasmic, and mitochondrial proteins as well as the effects of such post-translational modifications are currently the focus of extensive research. 29279740 1 7 theme O-GlcNAc 241:248 arg1 OGT 294:296 OGT 294:296 OGT 294:296 STUDY DESIGN Human herniated discs were obtained from discectomy specimens for the immunohistochemical detection of O-GlcNAc and O-GlcNAcase (OGA)/O-GlcNAc transferase (OGT). 29279740 1 7 theme O-GlcNAc 241:248 arg1 transferase 281:291 O-GlcNAc and O-GlcNAcase (OGA)/O-GlcNAc transferase 241:291 transferase 281:291 STUDY DESIGN Human herniated discs were obtained from discectomy specimens for the immunohistochemical detection of O-GlcNAc and O-GlcNAcase (OGA)/O-GlcNAc transferase (OGT). 29279740 6 8 theme degeneration 994:1005 arg1 O-GlcNAcylation 951:965 O-GlcNAcylation 951:965 O-GlcNAcylation 951:965 We believe that O-GlcNAcylation is a key regulator of disc degeneration. 29279740 6 8 theme degeneration 994:1005 arg1 regulator 976:984 a key regulator 970:984 a key regulator of disc degeneration 970:1005 We believe that O-GlcNAcylation is a key regulator of disc degeneration. 29279740 7 9 theme formaldehyde 1098:1109 arg1 solution 1069:1076 a 10% solution 1063:1076 a 10% solution of neutral-buffered formaldehyde 1063:1109 METHODS Fifty-six specimens were fixed for 24 hours in a 10% solution of neutral-buffered formaldehyde, dehydrated, and embedded in paraffin. 29279740 9 10 theme proteins 1297:1304 arg1 O-GlcNAcylation 1266:1280 O-GlcNAcylation 1266:1280 O-GlcNAcylation of cytoplasmic proteins 1266:1304 RESULTS We found that O-GlcNAcylation of cytoplasmic proteins was less than that of nuclear proteins in both single cells and cell clusters. 29279740 3 11 theme extensive 633:641 arg1 research 643:650 extensive research 633:650 extensive research 633:650 OVERVIEW OF LITERATURE The O-GlcNAcylation of nuclear, cytoplasmic, and mitochondrial proteins as well as the effects of such post-translational modifications are currently the focus of extensive research. 29279740 1 12 theme O-GlcNAcase 254:264 arg1 OGT 294:296 OGT 294:296 OGT 294:296 STUDY DESIGN Human herniated discs were obtained from discectomy specimens for the immunohistochemical detection of O-GlcNAc and O-GlcNAcase (OGA)/O-GlcNAc transferase (OGT). 29279740 1 12 theme O-GlcNAcase 254:264 arg1 transferase 281:291 O-GlcNAc and O-GlcNAcase (OGA)/O-GlcNAc transferase 241:291 transferase 281:291 STUDY DESIGN Human herniated discs were obtained from discectomy specimens for the immunohistochemical detection of O-GlcNAc and O-GlcNAcase (OGA)/O-GlcNAc transferase (OGT). 29279740 12 13 theme first 1660:1664 arg1 time 1666:1669 the first time 1656:1669 the first time 1656:1669 CONCLUSIONS O-GlcNAc and OGA/OGT expression is shown to correlate for the first time with intervertebral disc cell degeneration. 29279740 4 14 theme nutrient 747:754 arg1 sensor 767:772 a nutrient and stress sensor 745:772 sensor 767:772 O-GlcNAcylation is believed to contribute to the etiology of chronic illnesses by acting as a nutrient and stress sensor in the cellular environment. 29279740 1 15 theme herniated 144:152 arg1 discs 154:158 Human herniated discs 138:158 Human herniated discs 138:158 STUDY DESIGN Human herniated discs were obtained from discectomy specimens for the immunohistochemical detection of O-GlcNAc and O-GlcNAcase (OGA)/O-GlcNAc transferase (OGT). 29279740 6 16 theme key 972:974 arg1 O-GlcNAcylation 951:965 O-GlcNAcylation 951:965 O-GlcNAcylation 951:965 We believe that O-GlcNAcylation is a key regulator of disc degeneration. 29279740 6 16 theme key 972:974 arg1 regulator 976:984 a key regulator 970:984 a key regulator of disc degeneration 970:1005 We believe that O-GlcNAcylation is a key regulator of disc degeneration. 29279740 4 17 theme stress 760:765 arg1 sensor 767:772 a nutrient and stress sensor 745:772 sensor 767:772 O-GlcNAcylation is believed to contribute to the etiology of chronic illnesses by acting as a nutrient and stress sensor in the cellular environment. 29279740 1 18 theme STUDY 125:129 arg1 DESIGN 131:136 STUDY DESIGN 125:136 STUDY DESIGN Human herniated discs were obtained from discectomy specimens for the immunohistochemical detection of O-GlcNAc and O-GlcNAcase (OGA)/O-GlcNAc transferase (OGT). 125:298 STUDY DESIGN Human herniated discs were obtained from discectomy specimens for the immunohistochemical detection of O-GlcNAc and O-GlcNAcase (OGA)/O-GlcNAc transferase (OGT). 29279740 7 19 theme % 1067:1067 arg1 solution 1069:1076 a 10% solution 1063:1076 a 10% solution of neutral-buffered formaldehyde 1063:1109 METHODS Fifty-six specimens were fixed for 24 hours in a 10% solution of neutral-buffered formaldehyde, dehydrated, and embedded in paraffin. 29279740 2 20 dep PURPOSE 300:306 arg1 aimed 319:323 aimed 319:323 aimed to quantify the extent of O-GlcNAcylation and its associated enzymes (OGT/OGA) in human degenerated intervertebral discs 319:444 PURPOSE This study aimed to quantify the extent of O-GlcNAcylation and its associated enzymes (OGT/OGA) in human degenerated intervertebral discs. 29279740 9 21 theme nuclear 1328:1334 arg1 proteins 1336:1343 nuclear proteins 1328:1343 nuclear proteins in both single cells and cell clusters 1328:1382 RESULTS We found that O-GlcNAcylation of cytoplasmic proteins was less than that of nuclear proteins in both single cells and cell clusters. 29279740 13 22 theme cytoplasmic 1810:1820 arg1 proteins 1822:1829 both nuclear and cytoplasmic proteins 1793:1829 both nuclear and cytoplasmic proteins in human disc cells 1793:1849 Increasing disc degeneration is associated with increasing O-GlcNAcylation in both nuclear and cytoplasmic proteins in human disc cells. 29279740 0 23 theme Degenerated 91:101 arg1 Discs 118:122 Human Degenerated Intervertebral Discs 85:122 Human Degenerated Intervertebral Discs 85:122 Detection of O-Linked-N-Acetylglucosamine Modification and Its Associated Enzymes in Human Degenerated Intervertebral Discs. 29279740 7 24 theme METHODS 1008:1014 arg1 specimens 1026:1034 METHODS Fifty-six specimens 1008:1034 METHODS Fifty-six specimens 1008:1034 METHODS Fifty-six specimens were fixed for 24 hours in a 10% solution of neutral-buffered formaldehyde, dehydrated, and embedded in paraffin. 29279740 0 25 from Detection 0:8 arg1 Discs 118:122 Human Degenerated Intervertebral Discs 85:122 Human Degenerated Intervertebral Discs 85:122 Detection of O-Linked-N-Acetylglucosamine Modification and Its Associated Enzymes in Human Degenerated Intervertebral Discs. 29279740 12 26 dep CONCLUSIONS 1586:1596 arg1 CONCLUSIONS 1586:1596 CONCLUSIONS O-GlcNAc and OGA/OGT 1586:1617 CONCLUSIONS O-GlcNAc and OGA/OGT expression 1586:1628 CONCLUSIONS O-GlcNAc and OGA/OGT expression is shown to correlate for the first time with intervertebral disc cell degeneration. 29279740 12 26 dep CONCLUSIONS 1586:1596 arg1 OGA/OGT 1611:1617 OGA/OGT 1611:1617 OGA/OGT 1611:1617 CONCLUSIONS O-GlcNAc and OGA/OGT expression is shown to correlate for the first time with intervertebral disc cell degeneration. 29279740 12 26 dep CONCLUSIONS 1586:1596 arg1 O-GlcNAc 1598:1605 O-GlcNAc 1598:1605 O-GlcNAc 1598:1605 CONCLUSIONS O-GlcNAc and OGA/OGT expression is shown to correlate for the first time with intervertebral disc cell degeneration. 29279740 9 27 theme single 1353:1358 arg1 cells 1360:1364 single cells 1353:1364 single cells 1353:1364 RESULTS We found that O-GlcNAcylation of cytoplasmic proteins was less than that of nuclear proteins in both single cells and cell clusters. 29279740 11 28 theme O-GlcNAc 1517:1524 arg1 levels 1537:1542 OGT and O-GlcNAc expression levels 1509:1542 OGT and O-GlcNAc expression levels 1509:1542 OGT and O-GlcNAc expression levels were identical in all specimens examined. 29279740 2 29 theme human 407:411 arg1 discs 440:444 human degenerated intervertebral discs 407:444 human degenerated intervertebral discs 407:444 PURPOSE This study aimed to quantify the extent of O-GlcNAcylation and its associated enzymes (OGT/OGA) in human degenerated intervertebral discs. 29279740 13 30 theme nuclear 1798:1804 arg1 proteins 1822:1829 both nuclear and cytoplasmic proteins 1793:1829 both nuclear and cytoplasmic proteins in human disc cells 1793:1849 Increasing disc degeneration is associated with increasing O-GlcNAcylation in both nuclear and cytoplasmic proteins in human disc cells. 29279740 11 31 theme OGT 1509:1511 arg1 levels 1537:1542 OGT and O-GlcNAc expression levels 1509:1542 OGT and O-GlcNAc expression levels 1509:1542 OGT and O-GlcNAc expression levels were identical in all specimens examined. 29279740 4 32 theme cellular 781:788 arg1 environment 790:800 the cellular environment 777:800 the cellular environment 777:800 O-GlcNAcylation is believed to contribute to the etiology of chronic illnesses by acting as a nutrient and stress sensor in the cellular environment. 29279740 3 33 theme nuclear 493:499 arg1 proteins 533:540 nuclear, cytoplasmic, and mitochondrial proteins 493:540 nuclear, cytoplasmic, and mitochondrial proteins 493:540 OVERVIEW OF LITERATURE The O-GlcNAcylation of nuclear, cytoplasmic, and mitochondrial proteins as well as the effects of such post-translational modifications are currently the focus of extensive research. 29279740 0 34 theme O-Linked-N-Acetylglucosamine 13:40 arg1 Modification 42:53 O-Linked-N-Acetylglucosamine Modification 13:53 O-Linked-N-Acetylglucosamine Modification 13:53 Detection of O-Linked-N-Acetylglucosamine Modification and Its Associated Enzymes in Human Degenerated Intervertebral Discs. 29279740 12 35 theme CONCLUSIONS 1586:1596 arg1 expression 1619:1628 CONCLUSIONS O-GlcNAc and OGA/OGT expression 1586:1628 CONCLUSIONS O-GlcNAc and OGA/OGT expression 1586:1628 CONCLUSIONS O-GlcNAc and OGA/OGT expression is shown to correlate for the first time with intervertebral disc cell degeneration. 29279740 2 36 theme intervertebral 425:438 arg1 discs 440:444 human degenerated intervertebral discs 407:444 human degenerated intervertebral discs 407:444 PURPOSE This study aimed to quantify the extent of O-GlcNAcylation and its associated enzymes (OGT/OGA) in human degenerated intervertebral discs. 29279740 13 37 theme Increasing 1715:1724 arg1 degeneration 1731:1742 Increasing disc degeneration 1715:1742 Increasing disc degeneration 1715:1742 Increasing disc degeneration is associated with increasing O-GlcNAcylation in both nuclear and cytoplasmic proteins in human disc cells. 29279740 10 38 theme Cytoplasmic 1385:1395 arg1 O-GlcNAcylation 1397:1411 Cytoplasmic O-GlcNAcylation 1385:1411 Cytoplasmic O-GlcNAcylation 1385:1411 Cytoplasmic O-GlcNAcylation occurs subsequent to nuclear O-GlcNAcylation and is directly proportional to disc degeneration. 29279740 5 39 theme chondrocyte-like 840:855 arg1 cells 830:834 Mature intervertebral disc cells 803:834 Mature intervertebral disc cells 803:834 Mature intervertebral disc cells are chondrocyte-like cells, and O-GlcNAc has been shown to promote chondrocyte apoptosis in vitro. 29279740 5 39 theme chondrocyte-like 840:855 arg1 cells 857:861 chondrocyte-like cells 840:861 chondrocyte-like cells 840:861 Mature intervertebral disc cells are chondrocyte-like cells, and O-GlcNAc has been shown to promote chondrocyte apoptosis in vitro. 29279740 11 40 from identical 1549:1557 arg1 specimens 1566:1574 all specimens 1562:1574 all specimens examined 1562:1583 OGT and O-GlcNAc expression levels were identical in all specimens examined. 29279740 3 41 theme cytoplasmic 502:512 arg1 proteins 533:540 nuclear, cytoplasmic, and mitochondrial proteins 493:540 nuclear, cytoplasmic, and mitochondrial proteins 493:540 OVERVIEW OF LITERATURE The O-GlcNAcylation of nuclear, cytoplasmic, and mitochondrial proteins as well as the effects of such post-translational modifications are currently the focus of extensive research. 29279740 8 42 theme Tissue 1150:1155 arg1 4-µm-thick 1165:1174 4-µm-thick 1165:1174 4-µm-thick 1165:1174 Tissue slices (4-µm-thick) were used for hematoxylin-eosin staining and immunohistochemistry. 29279740 8 42 theme Tissue 1150:1155 arg1 slices 1157:1162 Tissue slices 1150:1162 Tissue slices (4-µm-thick) 1150:1175 Tissue slices (4-µm-thick) were used for hematoxylin-eosin staining and immunohistochemistry. 29279740 1 43 dep DESIGN 131:136 arg1 obtained 165:172 obtained 165:172 were obtained from discectomy specimens for the immunohistochemical detection of O-GlcNAc and O-GlcNAcase (OGA)/O-GlcNAc transferase (OGT) 160:297 STUDY DESIGN Human herniated discs were obtained from discectomy specimens for the immunohistochemical detection of O-GlcNAc and O-GlcNAcase (OGA)/O-GlcNAc transferase (OGT). 29279740 5 44 theme Mature 803:808 arg1 cells 830:834 Mature intervertebral disc cells 803:834 Mature intervertebral disc cells 803:834 Mature intervertebral disc cells are chondrocyte-like cells, and O-GlcNAc has been shown to promote chondrocyte apoptosis in vitro. 29279740 5 44 theme Mature 803:808 arg1 cells 857:861 chondrocyte-like cells 840:861 chondrocyte-like cells 840:861 Mature intervertebral disc cells are chondrocyte-like cells, and O-GlcNAc has been shown to promote chondrocyte apoptosis in vitro. 29279740 2 45 theme associated 375:384 arg1 OGT/OGA 395:401 OGT/OGA 395:401 OGT/OGA 395:401 PURPOSE This study aimed to quantify the extent of O-GlcNAcylation and its associated enzymes (OGT/OGA) in human degenerated intervertebral discs. 29279740 2 45 theme associated 375:384 arg1 enzymes 386:392 its associated enzymes 371:392 its associated enzymes (OGT/OGA) 371:402 PURPOSE This study aimed to quantify the extent of O-GlcNAcylation and its associated enzymes (OGT/OGA) in human degenerated intervertebral discs. 29279740 1 46 theme transferase 281:291 arg1 detection 228:236 the immunohistochemical detection 204:236 the immunohistochemical detection of O-GlcNAc and O-GlcNAcase (OGA)/O-GlcNAc transferase (OGT) 204:297 STUDY DESIGN Human herniated discs were obtained from discectomy specimens for the immunohistochemical detection of O-GlcNAc and O-GlcNAcase (OGA)/O-GlcNAc transferase (OGT). 29279740 8 47 theme hematoxylin-eosin 1191:1207 arg1 staining 1209:1216 hematoxylin-eosin staining 1191:1216 hematoxylin-eosin staining 1191:1216 Tissue slices (4-µm-thick) were used for hematoxylin-eosin staining and immunohistochemistry. 29279740 5 48 theme intervertebral 810:823 arg1 cells 830:834 Mature intervertebral disc cells 803:834 Mature intervertebral disc cells 803:834 Mature intervertebral disc cells are chondrocyte-like cells, and O-GlcNAc has been shown to promote chondrocyte apoptosis in vitro. 29279740 5 48 theme intervertebral 810:823 arg1 cells 857:861 chondrocyte-like cells 840:861 chondrocyte-like cells 840:861 Mature intervertebral disc cells are chondrocyte-like cells, and O-GlcNAc has been shown to promote chondrocyte apoptosis in vitro. 29279740 10 49 theme disc 1490:1493 arg1 degeneration 1495:1506 disc degeneration 1490:1506 disc degeneration 1490:1506 Cytoplasmic O-GlcNAcylation occurs subsequent to nuclear O-GlcNAcylation and is directly proportional to disc degeneration. 29279740 1 50 theme immunohistochemical 208:226 arg1 detection 228:236 the immunohistochemical detection 204:236 the immunohistochemical detection of O-GlcNAc and O-GlcNAcase (OGA)/O-GlcNAc transferase (OGT) 204:297 STUDY DESIGN Human herniated discs were obtained from discectomy specimens for the immunohistochemical detection of O-GlcNAc and O-GlcNAcase (OGA)/O-GlcNAc transferase (OGT). 29279740 12 51 theme cell 1696:1699 arg1 degeneration 1701:1712 intervertebral disc cell degeneration 1676:1712 intervertebral disc cell degeneration 1676:1712 CONCLUSIONS O-GlcNAc and OGA/OGT expression is shown to correlate for the first time with intervertebral disc cell degeneration. 29279740 0 52 theme Associated 63:72 arg1 Enzymes 74:80 Its Associated Enzymes 59:80 Its Associated Enzymes 59:80 Detection of O-Linked-N-Acetylglucosamine Modification and Its Associated Enzymes in Human Degenerated Intervertebral Discs. 29279740 3 53 theme post-translational 573:590 arg1 modifications 592:604 such post-translational modifications 568:604 such post-translational modifications 568:604 OVERVIEW OF LITERATURE The O-GlcNAcylation of nuclear, cytoplasmic, and mitochondrial proteins as well as the effects of such post-translational modifications are currently the focus of extensive research. 29279740 7 54 from hours 1054:1058 arg1 solution 1069:1076 a 10% solution 1063:1076 a 10% solution of neutral-buffered formaldehyde 1063:1109 METHODS Fifty-six specimens were fixed for 24 hours in a 10% solution of neutral-buffered formaldehyde, dehydrated, and embedded in paraffin. 29279740 13 55 theme disc 1840:1843 arg1 cells 1845:1849 human disc cells 1834:1849 human disc cells 1834:1849 Increasing disc degeneration is associated with increasing O-GlcNAcylation in both nuclear and cytoplasmic proteins in human disc cells. 29279740 3 56 theme mitochondrial 519:531 arg1 proteins 533:540 nuclear, cytoplasmic, and mitochondrial proteins 493:540 nuclear, cytoplasmic, and mitochondrial proteins 493:540 OVERVIEW OF LITERATURE The O-GlcNAcylation of nuclear, cytoplasmic, and mitochondrial proteins as well as the effects of such post-translational modifications are currently the focus of extensive research. 29279740 7 57 theme neutral-buffered 1081:1096 arg1 formaldehyde 1098:1109 neutral-buffered formaldehyde 1081:1109 neutral-buffered formaldehyde 1081:1109 METHODS Fifty-six specimens were fixed for 24 hours in a 10% solution of neutral-buffered formaldehyde, dehydrated, and embedded in paraffin. 29279740 9 58 theme cytoplasmic 1285:1295 arg1 proteins 1297:1304 cytoplasmic proteins 1285:1304 cytoplasmic proteins 1285:1304 RESULTS We found that O-GlcNAcylation of cytoplasmic proteins was less than that of nuclear proteins in both single cells and cell clusters. 29279740 6 59 theme disc 989:992 arg1 degeneration 994:1005 disc degeneration 989:1005 disc degeneration 989:1005 We believe that O-GlcNAcylation is a key regulator of disc degeneration. 29279740 3 60 theme proteins 533:540 arg1 O-GlcNAcylation 474:488 The O-GlcNAcylation 470:488 OVERVIEW OF LITERATURE The O-GlcNAcylation of nuclear, cytoplasmic, and mitochondrial proteins as well as the effects of such post-translational modifications 447:604 OVERVIEW OF LITERATURE The O-GlcNAcylation of nuclear, cytoplasmic, and mitochondrial proteins as well as the effects of such post-translational modifications are currently the focus of extensive research. 29279740 1 61 theme Human 138:142 arg1 discs 154:158 Human herniated discs 138:158 Human herniated discs 138:158 STUDY DESIGN Human herniated discs were obtained from discectomy specimens for the immunohistochemical detection of O-GlcNAc and O-GlcNAcase (OGA)/O-GlcNAc transferase (OGT). 29279740 9 62 from proteins 1336:1343 arg1 cells 1360:1364 single cells 1353:1364 single cells 1353:1364 RESULTS We found that O-GlcNAcylation of cytoplasmic proteins was less than that of nuclear proteins in both single cells and cell clusters. 29279740 9 62 from proteins 1336:1343 arg1 clusters 1375:1382 cell clusters 1370:1382 cell clusters 1370:1382 RESULTS We found that O-GlcNAcylation of cytoplasmic proteins was less than that of nuclear proteins in both single cells and cell clusters. 29279740 12 63 theme intervertebral 1676:1689 arg1 degeneration 1701:1712 intervertebral disc cell degeneration 1676:1712 intervertebral disc cell degeneration 1676:1712 CONCLUSIONS O-GlcNAc and OGA/OGT expression is shown to correlate for the first time with intervertebral disc cell degeneration. 29279740 7 64 theme 10 1065:1066 arg1 % 1067:1067 % 1067:1067 % 1067:1067 METHODS Fifty-six specimens were fixed for 24 hours in a 10% solution of neutral-buffered formaldehyde, dehydrated, and embedded in paraffin. 29279740 9 65 dep RESULTS 1244:1250 arg1 found 1255:1259 found 1255:1259 found that O-GlcNAcylation of cytoplasmic proteins was less than that of nuclear proteins in both single cells and cell clusters 1255:1382 RESULTS We found that O-GlcNAcylation of cytoplasmic proteins was less than that of nuclear proteins in both single cells and cell clusters. 29279740 0 66 theme Human 85:89 arg1 Discs 118:122 Human Degenerated Intervertebral Discs 85:122 Human Degenerated Intervertebral Discs 85:122 Detection of O-Linked-N-Acetylglucosamine Modification and Its Associated Enzymes in Human Degenerated Intervertebral Discs. 29279740 3 67 theme research 643:650 arg1 OVERVIEW 447:454 OVERVIEW 447:454 OVERVIEW OF LITERATURE The O-GlcNAcylation of nuclear, cytoplasmic, and mitochondrial proteins as well as the effects of such post-translational modifications 447:604 OVERVIEW OF LITERATURE The O-GlcNAcylation of nuclear, cytoplasmic, and mitochondrial proteins as well as the effects of such post-translational modifications are currently the focus of extensive research. 29279740 3 67 theme research 643:650 arg1 focus 624:628 the focus 620:628 the focus of extensive research 620:650 OVERVIEW OF LITERATURE The O-GlcNAcylation of nuclear, cytoplasmic, and mitochondrial proteins as well as the effects of such post-translational modifications are currently the focus of extensive research. 29279740 3 67 theme research 643:650 arg1 effects 557:563 the effects 553:563 OVERVIEW OF LITERATURE The O-GlcNAcylation of nuclear, cytoplasmic, and mitochondrial proteins as well as the effects of such post-translational modifications 447:604 OVERVIEW OF LITERATURE The O-GlcNAcylation of nuclear, cytoplasmic, and mitochondrial proteins as well as the effects of such post-translational modifications are currently the focus of extensive research. 29279740 4 68 theme illnesses 722:730 arg1 etiology 702:709 the etiology 698:709 the etiology of chronic illnesses 698:730 O-GlcNAcylation is believed to contribute to the etiology of chronic illnesses by acting as a nutrient and stress sensor in the cellular environment. 29279740 0 69 theme Intervertebral 103:116 arg1 Discs 118:122 Human Degenerated Intervertebral Discs 85:122 Human Degenerated Intervertebral Discs 85:122 Detection of O-Linked-N-Acetylglucosamine Modification and Its Associated Enzymes in Human Degenerated Intervertebral Discs. 29279740 1 70 theme discectomy 179:188 arg1 specimens 190:198 discectomy specimens 179:198 discectomy specimens for the immunohistochemical detection of O-GlcNAc and O-GlcNAcase (OGA)/O-GlcNAc transferase (OGT) 179:297 STUDY DESIGN Human herniated discs were obtained from discectomy specimens for the immunohistochemical detection of O-GlcNAc and O-GlcNAcase (OGA)/O-GlcNAc transferase (OGT). 29279740 7 71 theme Fifty-six 1016:1024 arg1 specimens 1026:1034 METHODS Fifty-six specimens 1008:1034 METHODS Fifty-six specimens 1008:1034 METHODS Fifty-six specimens were fixed for 24 hours in a 10% solution of neutral-buffered formaldehyde, dehydrated, and embedded in paraffin. 29279740 13 72 theme human 1834:1838 arg1 cells 1845:1849 human disc cells 1834:1849 human disc cells 1834:1849 Increasing disc degeneration is associated with increasing O-GlcNAcylation in both nuclear and cytoplasmic proteins in human disc cells. 29279740 9 73 theme cell 1370:1373 arg1 clusters 1375:1382 cell clusters 1370:1382 cell clusters 1370:1382 RESULTS We found that O-GlcNAcylation of cytoplasmic proteins was less than that of nuclear proteins in both single cells and cell clusters. 29279740 0 74 theme Modification 42:53 arg1 Detection 0:8 Detection 0:8 Detection of O-Linked-N-Acetylglucosamine Modification and Its Associated Enzymes in Human Degenerated Intervertebral Discs. 0:123 Detection of O-Linked-N-Acetylglucosamine Modification and Its Associated Enzymes in Human Degenerated Intervertebral Discs. 29279740 4 75 from sensor 767:772 arg1 environment 790:800 the cellular environment 777:800 the cellular environment 777:800 O-GlcNAcylation is believed to contribute to the etiology of chronic illnesses by acting as a nutrient and stress sensor in the cellular environment. 29279740 11 76 from specimens 1566:1574 arg1 identical 1549:1557 identical 1549:1557 identical 1549:1557 OGT and O-GlcNAc expression levels were identical in all specimens examined. 29279740 7 77 from embedded 1128:1135 arg1 paraffin 1140:1147 paraffin 1140:1147 paraffin 1140:1147 METHODS Fifty-six specimens were fixed for 24 hours in a 10% solution of neutral-buffered formaldehyde, dehydrated, and embedded in paraffin. 29279740 11 78 theme expression 1526:1535 arg1 levels 1537:1542 OGT and O-GlcNAc expression levels 1509:1542 OGT and O-GlcNAc expression levels 1509:1542 OGT and O-GlcNAc expression levels were identical in all specimens examined. 29279740 5 79 theme disc 825:828 arg1 cells 830:834 Mature intervertebral disc cells 803:834 Mature intervertebral disc cells 803:834 Mature intervertebral disc cells are chondrocyte-like cells, and O-GlcNAc has been shown to promote chondrocyte apoptosis in vitro. 29279740 5 79 theme disc 825:828 arg1 cells 857:861 chondrocyte-like cells 840:861 chondrocyte-like cells 840:861 Mature intervertebral disc cells are chondrocyte-like cells, and O-GlcNAc has been shown to promote chondrocyte apoptosis in vitro. 29279740 3 80 dep OVERVIEW 447:454 arg1 O-GlcNAcylation 474:488 The O-GlcNAcylation 470:488 OVERVIEW OF LITERATURE The O-GlcNAcylation of nuclear, cytoplasmic, and mitochondrial proteins as well as the effects of such post-translational modifications 447:604 OVERVIEW OF LITERATURE The O-GlcNAcylation of nuclear, cytoplasmic, and mitochondrial proteins as well as the effects of such post-translational modifications are currently the focus of extensive research. 29279740 3 81 theme LITERATURE 459:468 arg1 OVERVIEW 447:454 OVERVIEW 447:454 OVERVIEW OF LITERATURE The O-GlcNAcylation of nuclear, cytoplasmic, and mitochondrial proteins as well as the effects of such post-translational modifications 447:604 OVERVIEW OF LITERATURE The O-GlcNAcylation of nuclear, cytoplasmic, and mitochondrial proteins as well as the effects of such post-translational modifications are currently the focus of extensive research. 29279740 3 81 theme LITERATURE 459:468 arg1 effects 557:563 the effects 553:563 OVERVIEW OF LITERATURE The O-GlcNAcylation of nuclear, cytoplasmic, and mitochondrial proteins as well as the effects of such post-translational modifications 447:604 OVERVIEW OF LITERATURE The O-GlcNAcylation of nuclear, cytoplasmic, and mitochondrial proteins as well as the effects of such post-translational modifications are currently the focus of extensive research. 29279740 3 81 theme LITERATURE 459:468 arg1 focus 624:628 the focus 620:628 the focus of extensive research 620:650 OVERVIEW OF LITERATURE The O-GlcNAcylation of nuclear, cytoplasmic, and mitochondrial proteins as well as the effects of such post-translational modifications are currently the focus of extensive research. 29279740 7 82 from paraffin 1140:1147 arg1 embedded 1128:1135 embedded 1128:1135 embedded 1128:1135 METHODS Fifty-six specimens were fixed for 24 hours in a 10% solution of neutral-buffered formaldehyde, dehydrated, and embedded in paraffin. 29279740 2 83 theme degenerated 413:423 arg1 discs 440:444 human degenerated intervertebral discs 407:444 human degenerated intervertebral discs 407:444 PURPOSE This study aimed to quantify the extent of O-GlcNAcylation and its associated enzymes (OGT/OGA) in human degenerated intervertebral discs. 29279740 0 84 theme Enzymes 74:80 arg1 Detection 0:8 Detection 0:8 Detection of O-Linked-N-Acetylglucosamine Modification and Its Associated Enzymes in Human Degenerated Intervertebral Discs. 0:123 Detection of O-Linked-N-Acetylglucosamine Modification and Its Associated Enzymes in Human Degenerated Intervertebral Discs. 29279740 13 85 theme disc 1726:1729 arg1 degeneration 1731:1742 Increasing disc degeneration 1715:1742 Increasing disc degeneration 1715:1742 Increasing disc degeneration is associated with increasing O-GlcNAcylation in both nuclear and cytoplasmic proteins in human disc cells. 29279740 2 86 theme O-GlcNAcylation 351:365 arg1 extent 341:346 the extent 337:346 the extent of O-GlcNAcylation and its associated enzymes (OGT/OGA) in human degenerated intervertebral discs 337:444 PURPOSE This study aimed to quantify the extent of O-GlcNAcylation and its associated enzymes (OGT/OGA) in human degenerated intervertebral discs. 29279740 13 87 from proteins 1822:1829 arg1 cells 1845:1849 human disc cells 1834:1849 human disc cells 1834:1849 Increasing disc degeneration is associated with increasing O-GlcNAcylation in both nuclear and cytoplasmic proteins in human disc cells. 29279740 10 88 theme nuclear 1434:1440 arg1 O-GlcNAcylation 1442:1456 nuclear O-GlcNAcylation 1434:1456 nuclear O-GlcNAcylation 1434:1456 Cytoplasmic O-GlcNAcylation occurs subsequent to nuclear O-GlcNAcylation and is directly proportional to disc degeneration. 29279740 1 89 theme OGA 267:269 arg1 OGT 294:296 OGT 294:296 OGT 294:296 STUDY DESIGN Human herniated discs were obtained from discectomy specimens for the immunohistochemical detection of O-GlcNAc and O-GlcNAcase (OGA)/O-GlcNAc transferase (OGT). 29279740 1 89 theme OGA 267:269 arg1 transferase 281:291 O-GlcNAc and O-GlcNAcase (OGA)/O-GlcNAc transferase 241:291 transferase 281:291 STUDY DESIGN Human herniated discs were obtained from discectomy specimens for the immunohistochemical detection of O-GlcNAc and O-GlcNAcase (OGA)/O-GlcNAc transferase (OGT). 29279740 2 90 theme enzymes 386:392 arg1 extent 341:346 the extent 337:346 the extent of O-GlcNAcylation and its associated enzymes (OGT/OGA) in human degenerated intervertebral discs 337:444 PURPOSE This study aimed to quantify the extent of O-GlcNAcylation and its associated enzymes (OGT/OGA) in human degenerated intervertebral discs. 29279740 1 91 theme /O-GlcNAc 271:279 arg1 OGT 294:296 OGT 294:296 OGT 294:296 STUDY DESIGN Human herniated discs were obtained from discectomy specimens for the immunohistochemical detection of O-GlcNAc and O-GlcNAcase (OGA)/O-GlcNAc transferase (OGT). 29279740 1 91 theme /O-GlcNAc 271:279 arg1 transferase 281:291 O-GlcNAc and O-GlcNAcase (OGA)/O-GlcNAc transferase 241:291 transferase 281:291 STUDY DESIGN Human herniated discs were obtained from discectomy specimens for the immunohistochemical detection of O-GlcNAc and O-GlcNAcase (OGA)/O-GlcNAc transferase (OGT). 28946365 3 0 theme non-acylated 715:726 arg1 anthocyanins 728:739 the 3-O-linked non-acylated anthocyanins 700:739 the 3-O-linked non-acylated anthocyanins 700:739 The effect significantly decreased when the chain length of the 3-O-linked non-acylated anthocyanins was increased from mono- to di- to triglycosyl moieties, possibly due to steric interferences of bound sugars and co-pigments. 28946365 2 1 theme anthocyanin 606:616 arg1 complexes 629:637 intermolecular anthocyanin:co-pigment complexes 591:637 intermolecular anthocyanin:co-pigment complexes 591:637 Chlorogenic acid supplementation generally increased absorbance of non-acylated anthocyanins by up to 97.9 and 122.9% at pH 3.6 and 4.6, respectively, being mainly attributed to the formation of intermolecular anthocyanin:co-pigment complexes. 28946365 3 2 theme sugars 844:849 arg1 interferences 821:833 steric interferences 814:833 steric interferences of bound sugars 814:849 The effect significantly decreased when the chain length of the 3-O-linked non-acylated anthocyanins was increased from mono- to di- to triglycosyl moieties, possibly due to steric interferences of bound sugars and co-pigments. 28946365 0 3 theme acylated 67:74 arg1 cyanidin-3-O-glycosides 93:115 acylated and non-acylated cyanidin-3-O-glycosides 67:115 acylated and non-acylated cyanidin-3-O-glycosides 67:115 Effect of chlorogenic acid on spectral properties and stability of acylated and non-acylated cyanidin-3-O-glycosides. 28946365 2 4 theme intermolecular 591:604 arg1 complexes 629:637 intermolecular anthocyanin:co-pigment complexes 591:637 intermolecular anthocyanin:co-pigment complexes 591:637 Chlorogenic acid supplementation generally increased absorbance of non-acylated anthocyanins by up to 97.9 and 122.9% at pH 3.6 and 4.6, respectively, being mainly attributed to the formation of intermolecular anthocyanin:co-pigment complexes. 28946365 0 5 theme cyanidin-3-O-glycosides 93:115 arg1 stability 54:62 stability 54:62 stability 54:62 Effect of chlorogenic acid on spectral properties and stability of acylated and non-acylated cyanidin-3-O-glycosides. 28946365 0 5 theme cyanidin-3-O-glycosides 93:115 arg1 properties 39:48 spectral properties 30:48 spectral properties 30:48 Effect of chlorogenic acid on spectral properties and stability of acylated and non-acylated cyanidin-3-O-glycosides. 28946365 0 6 from Effect 0:5 arg1 stability 54:62 stability 54:62 stability 54:62 Effect of chlorogenic acid on spectral properties and stability of acylated and non-acylated cyanidin-3-O-glycosides. 28946365 0 6 from Effect 0:5 arg1 properties 39:48 spectral properties 30:48 spectral properties 30:48 Effect of chlorogenic acid on spectral properties and stability of acylated and non-acylated cyanidin-3-O-glycosides. 28946365 2 7 dep 97.9 498:501 arg1 to 495:496 to 495:496 to 495:496 Chlorogenic acid supplementation generally increased absorbance of non-acylated anthocyanins by up to 97.9 and 122.9% at pH 3.6 and 4.6, respectively, being mainly attributed to the formation of intermolecular anthocyanin:co-pigment complexes. 28946365 1 8 theme aqueous 274:280 arg1 pH 293:294 pH 3.6 and 4.6 293:306 pH 293:294 Spectral characteristics and heat stability (90°C, 5h) of six isolated, structurally related cyanidin-3-O-glycosides from black carrot were investigated in aqueous solutions (pH 3.6 and 4.6) supplemented with chlorogenic acid (molar anthocyanin:co-pigment ratios 1:62.5-1:250). 28946365 1 8 theme aqueous 274:280 arg1 4.6 304:306 4.6 304:306 4.6 304:306 Spectral characteristics and heat stability (90°C, 5h) of six isolated, structurally related cyanidin-3-O-glycosides from black carrot were investigated in aqueous solutions (pH 3.6 and 4.6) supplemented with chlorogenic acid (molar anthocyanin:co-pigment ratios 1:62.5-1:250). 28946365 1 8 theme aqueous 274:280 arg1 solutions 282:290 aqueous solutions 274:290 aqueous solutions (pH 3.6 and 4.6) supplemented with chlorogenic acid (molar anthocyanin:co-pigment ratios 1:62.5-1:250) 274:393 Spectral characteristics and heat stability (90°C, 5h) of six isolated, structurally related cyanidin-3-O-glycosides from black carrot were investigated in aqueous solutions (pH 3.6 and 4.6) supplemented with chlorogenic acid (molar anthocyanin:co-pigment ratios 1:62.5-1:250). 28946365 0 9 theme non-acylated 80:91 arg1 cyanidin-3-O-glycosides 93:115 acylated and non-acylated cyanidin-3-O-glycosides 67:115 acylated and non-acylated cyanidin-3-O-glycosides 67:115 Effect of chlorogenic acid on spectral properties and stability of acylated and non-acylated cyanidin-3-O-glycosides. 28946365 1 10 theme anthocyanin 351:361 arg1 ratios 374:379 molar anthocyanin:co-pigment ratios 345:379 molar anthocyanin:co-pigment ratios 1:62.5-1:250 345:392 Spectral characteristics and heat stability (90°C, 5h) of six isolated, structurally related cyanidin-3-O-glycosides from black carrot were investigated in aqueous solutions (pH 3.6 and 4.6) supplemented with chlorogenic acid (molar anthocyanin:co-pigment ratios 1:62.5-1:250). 28946365 3 11 theme bound 838:842 arg1 sugars 844:849 bound sugars 838:849 bound sugars 838:849 The effect significantly decreased when the chain length of the 3-O-linked non-acylated anthocyanins was increased from mono- to di- to triglycosyl moieties, possibly due to steric interferences of bound sugars and co-pigments. 28946365 1 12 dep characteristics 127:141 arg1 90°C 163:166 90°C 163:166 90°C 163:166 Spectral characteristics and heat stability (90°C, 5h) of six isolated, structurally related cyanidin-3-O-glycosides from black carrot were investigated in aqueous solutions (pH 3.6 and 4.6) supplemented with chlorogenic acid (molar anthocyanin:co-pigment ratios 1:62.5-1:250). 28946365 1 12 dep characteristics 127:141 arg1 5h 169:170 5h 169:170 5h 169:170 Spectral characteristics and heat stability (90°C, 5h) of six isolated, structurally related cyanidin-3-O-glycosides from black carrot were investigated in aqueous solutions (pH 3.6 and 4.6) supplemented with chlorogenic acid (molar anthocyanin:co-pigment ratios 1:62.5-1:250). 28946365 2 13 theme Chlorogenic 396:406 arg1 supplementation 413:427 Chlorogenic acid supplementation 396:427 Chlorogenic acid supplementation 396:427 Chlorogenic acid supplementation generally increased absorbance of non-acylated anthocyanins by up to 97.9 and 122.9% at pH 3.6 and 4.6, respectively, being mainly attributed to the formation of intermolecular anthocyanin:co-pigment complexes. 28946365 1 14 theme co-pigment 363:372 arg1 ratios 374:379 molar anthocyanin:co-pigment ratios 345:379 molar anthocyanin:co-pigment ratios 1:62.5-1:250 345:392 Spectral characteristics and heat stability (90°C, 5h) of six isolated, structurally related cyanidin-3-O-glycosides from black carrot were investigated in aqueous solutions (pH 3.6 and 4.6) supplemented with chlorogenic acid (molar anthocyanin:co-pigment ratios 1:62.5-1:250). 28946365 2 15 theme complexes 629:637 arg1 formation 578:586 the formation 574:586 the formation of intermolecular anthocyanin:co-pigment complexes 574:637 Chlorogenic acid supplementation generally increased absorbance of non-acylated anthocyanins by up to 97.9 and 122.9% at pH 3.6 and 4.6, respectively, being mainly attributed to the formation of intermolecular anthocyanin:co-pigment complexes. 28946365 6 16 theme Chlorogenic 1100:1110 arg1 acid 1112:1115 Chlorogenic acid 1100:1115 Chlorogenic acid addition 1100:1124 Chlorogenic acid addition evoked weak enhancement of thermal pigment stability at pH 3.6, while it was highly detrimental for all anthocyanins at pH 4.6. 28946365 2 17 theme anthocyanins 476:487 arg1 absorbance 449:458 absorbance 449:458 absorbance of non-acylated anthocyanins 449:487 Chlorogenic acid supplementation generally increased absorbance of non-acylated anthocyanins by up to 97.9 and 122.9% at pH 3.6 and 4.6, respectively, being mainly attributed to the formation of intermolecular anthocyanin:co-pigment complexes. 28946365 1 18 theme ratios 374:379 arg1 1:62.5-1:250 381:392 molar anthocyanin:co-pigment ratios 1:62.5-1:250 345:392 molar anthocyanin:co-pigment ratios 1:62.5-1:250 345:392 Spectral characteristics and heat stability (90°C, 5h) of six isolated, structurally related cyanidin-3-O-glycosides from black carrot were investigated in aqueous solutions (pH 3.6 and 4.6) supplemented with chlorogenic acid (molar anthocyanin:co-pigment ratios 1:62.5-1:250). 28946365 1 18 theme ratios 374:379 arg1 acid 339:342 chlorogenic acid 327:342 chlorogenic acid (molar anthocyanin:co-pigment ratios 1:62.5-1:250) 327:393 Spectral characteristics and heat stability (90°C, 5h) of six isolated, structurally related cyanidin-3-O-glycosides from black carrot were investigated in aqueous solutions (pH 3.6 and 4.6) supplemented with chlorogenic acid (molar anthocyanin:co-pigment ratios 1:62.5-1:250). 28946365 2 19 theme co-pigment 618:627 arg1 complexes 629:637 intermolecular anthocyanin:co-pigment complexes 591:637 intermolecular anthocyanin:co-pigment complexes 591:637 Chlorogenic acid supplementation generally increased absorbance of non-acylated anthocyanins by up to 97.9 and 122.9% at pH 3.6 and 4.6, respectively, being mainly attributed to the formation of intermolecular anthocyanin:co-pigment complexes. 28946365 1 20 from stability 152:160 arg1 carrot 246:251 black carrot 240:251 black carrot 240:251 Spectral characteristics and heat stability (90°C, 5h) of six isolated, structurally related cyanidin-3-O-glycosides from black carrot were investigated in aqueous solutions (pH 3.6 and 4.6) supplemented with chlorogenic acid (molar anthocyanin:co-pigment ratios 1:62.5-1:250). 28946365 4 21 theme first 924:928 arg1 time 930:933 the first time 920:933 the first time for feruloylated and sinapoylated cyanidin-3-O-triglycosides 920:994 Intermolecular co-pigmentation was investigated for the first time for feruloylated and sinapoylated cyanidin-3-O-triglycosides. 28946365 2 22 theme non-acylated 463:474 arg1 anthocyanins 476:487 non-acylated anthocyanins 463:487 non-acylated anthocyanins 463:487 Chlorogenic acid supplementation generally increased absorbance of non-acylated anthocyanins by up to 97.9 and 122.9% at pH 3.6 and 4.6, respectively, being mainly attributed to the formation of intermolecular anthocyanin:co-pigment complexes. 28946365 4 23 theme Intermolecular 868:881 arg1 co-pigmentation 883:897 Intermolecular co-pigmentation 868:897 Intermolecular co-pigmentation 868:897 Intermolecular co-pigmentation was investigated for the first time for feruloylated and sinapoylated cyanidin-3-O-triglycosides. 28946365 1 24 from characteristics 127:141 arg1 carrot 246:251 black carrot 240:251 black carrot 240:251 Spectral characteristics and heat stability (90°C, 5h) of six isolated, structurally related cyanidin-3-O-glycosides from black carrot were investigated in aqueous solutions (pH 3.6 and 4.6) supplemented with chlorogenic acid (molar anthocyanin:co-pigment ratios 1:62.5-1:250). 28946365 1 25 theme isolated 180:187 arg1 cyanidin-3-O-glycosides 211:233 six isolated, structurally related cyanidin-3-O-glycosides 176:233 six isolated, structurally related cyanidin-3-O-glycosides from black carrot 176:251 Spectral characteristics and heat stability (90°C, 5h) of six isolated, structurally related cyanidin-3-O-glycosides from black carrot were investigated in aqueous solutions (pH 3.6 and 4.6) supplemented with chlorogenic acid (molar anthocyanin:co-pigment ratios 1:62.5-1:250). 28946365 0 26 theme acid 22:25 arg1 Effect 0:5 Effect 0:5 Effect of chlorogenic acid on spectral properties and stability of acylated and non-acylated cyanidin-3-O-glycosides. 0:116 Effect of chlorogenic acid on spectral properties and stability of acylated and non-acylated cyanidin-3-O-glycosides. 28946365 4 27 theme sinapoylated 956:967 arg1 cyanidin-3-O-triglycosides 969:994 feruloylated and sinapoylated cyanidin-3-O-triglycosides 939:994 feruloylated and sinapoylated cyanidin-3-O-triglycosides 939:994 Intermolecular co-pigmentation was investigated for the first time for feruloylated and sinapoylated cyanidin-3-O-triglycosides. 28946365 5 28 theme weaker 1012:1017 arg1 effects 1019:1025 weaker effects 1012:1025 weaker effects (10.8-16.0%) 1012:1038 They exhibited weaker effects (10.8-16.0%) at pH 4.6, and no spectral response was observed at pH 3.6. 28946365 5 28 theme weaker 1012:1017 arg1 % 1037:1037 10.8-16.0% 1028:1037 10.8-16.0% 1028:1037 They exhibited weaker effects (10.8-16.0%) at pH 4.6, and no spectral response was observed at pH 3.6. 28946365 5 29 located observed 1080:1087 arg2 response 1067:1074 no spectral response 1055:1074 no spectral response 1055:1074 They exhibited weaker effects (10.8-16.0%) at pH 4.6, and no spectral response was observed at pH 3.6. 28946365 5 29 located observed 1080:1087 arg1 pH 1092:1093 pH 3.6 1092:1097 pH 3.6 1092:1097 They exhibited weaker effects (10.8-16.0%) at pH 4.6, and no spectral response was observed at pH 3.6. 28946365 0 30 theme chlorogenic 10:20 arg1 acid 22:25 chlorogenic acid 10:25 chlorogenic acid 10:25 Effect of chlorogenic acid on spectral properties and stability of acylated and non-acylated cyanidin-3-O-glycosides. 28946365 1 31 theme Spectral 118:125 arg1 characteristics 127:141 Spectral characteristics 118:141 Spectral characteristics 118:141 Spectral characteristics and heat stability (90°C, 5h) of six isolated, structurally related cyanidin-3-O-glycosides from black carrot were investigated in aqueous solutions (pH 3.6 and 4.6) supplemented with chlorogenic acid (molar anthocyanin:co-pigment ratios 1:62.5-1:250). 28946365 3 32 link 3-O-linked 704:713 arg1 anthocyanins 728:739 the 3-O-linked non-acylated anthocyanins 700:739 the 3-O-linked non-acylated anthocyanins 700:739 The effect significantly decreased when the chain length of the 3-O-linked non-acylated anthocyanins was increased from mono- to di- to triglycosyl moieties, possibly due to steric interferences of bound sugars and co-pigments. 28946365 0 33 theme spectral 30:37 arg1 properties 39:48 spectral properties 30:48 spectral properties 30:48 Effect of chlorogenic acid on spectral properties and stability of acylated and non-acylated cyanidin-3-O-glycosides. 28946365 6 34 theme acid 1112:1115 arg1 addition 1117:1124 Chlorogenic acid addition 1100:1124 Chlorogenic acid addition 1100:1124 Chlorogenic acid addition evoked weak enhancement of thermal pigment stability at pH 3.6, while it was highly detrimental for all anthocyanins at pH 4.6. 28946365 6 35 theme thermal 1153:1159 arg1 stability 1169:1177 thermal pigment stability 1153:1177 thermal pigment stability 1153:1177 Chlorogenic acid addition evoked weak enhancement of thermal pigment stability at pH 3.6, while it was highly detrimental for all anthocyanins at pH 4.6. 28946365 1 36 dep isolated 180:187 arg1 related 203:209 related 203:209 related 203:209 Spectral characteristics and heat stability (90°C, 5h) of six isolated, structurally related cyanidin-3-O-glycosides from black carrot were investigated in aqueous solutions (pH 3.6 and 4.6) supplemented with chlorogenic acid (molar anthocyanin:co-pigment ratios 1:62.5-1:250). 28946365 1 37 theme cyanidin-3-O-glycosides 211:233 arg1 characteristics 127:141 Spectral characteristics 118:141 Spectral characteristics 118:141 Spectral characteristics and heat stability (90°C, 5h) of six isolated, structurally related cyanidin-3-O-glycosides from black carrot were investigated in aqueous solutions (pH 3.6 and 4.6) supplemented with chlorogenic acid (molar anthocyanin:co-pigment ratios 1:62.5-1:250). 28946365 1 37 theme cyanidin-3-O-glycosides 211:233 arg1 stability 152:160 heat stability 147:160 heat stability 147:160 Spectral characteristics and heat stability (90°C, 5h) of six isolated, structurally related cyanidin-3-O-glycosides from black carrot were investigated in aqueous solutions (pH 3.6 and 4.6) supplemented with chlorogenic acid (molar anthocyanin:co-pigment ratios 1:62.5-1:250). 28946365 1 38 from carrot 246:251 arg1 characteristics 127:141 Spectral characteristics 118:141 Spectral characteristics 118:141 Spectral characteristics and heat stability (90°C, 5h) of six isolated, structurally related cyanidin-3-O-glycosides from black carrot were investigated in aqueous solutions (pH 3.6 and 4.6) supplemented with chlorogenic acid (molar anthocyanin:co-pigment ratios 1:62.5-1:250). 28946365 1 38 from carrot 246:251 arg1 stability 152:160 heat stability 147:160 heat stability 147:160 Spectral characteristics and heat stability (90°C, 5h) of six isolated, structurally related cyanidin-3-O-glycosides from black carrot were investigated in aqueous solutions (pH 3.6 and 4.6) supplemented with chlorogenic acid (molar anthocyanin:co-pigment ratios 1:62.5-1:250). 28946365 1 38 from carrot 246:251 arg1 cyanidin-3-O-glycosides 211:233 six isolated, structurally related cyanidin-3-O-glycosides 176:233 six isolated, structurally related cyanidin-3-O-glycosides from black carrot 176:251 Spectral characteristics and heat stability (90°C, 5h) of six isolated, structurally related cyanidin-3-O-glycosides from black carrot were investigated in aqueous solutions (pH 3.6 and 4.6) supplemented with chlorogenic acid (molar anthocyanin:co-pigment ratios 1:62.5-1:250). 28946365 5 39 theme spectral 1058:1065 arg1 response 1067:1074 no spectral response 1055:1074 no spectral response 1055:1074 They exhibited weaker effects (10.8-16.0%) at pH 4.6, and no spectral response was observed at pH 3.6. 28946365 3 40 theme anthocyanins 728:739 arg1 length 690:695 the chain length 680:695 the chain length of the 3-O-linked non-acylated anthocyanins 680:739 The effect significantly decreased when the chain length of the 3-O-linked non-acylated anthocyanins was increased from mono- to di- to triglycosyl moieties, possibly due to steric interferences of bound sugars and co-pigments. 28946365 6 41 theme stability 1169:1177 arg1 enhancement 1138:1148 weak enhancement 1133:1148 weak enhancement of thermal pigment stability 1133:1177 Chlorogenic acid addition evoked weak enhancement of thermal pigment stability at pH 3.6, while it was highly detrimental for all anthocyanins at pH 4.6. 28946365 1 42 theme molar 345:349 arg1 ratios 374:379 molar anthocyanin:co-pigment ratios 345:379 molar anthocyanin:co-pigment ratios 1:62.5-1:250 345:392 Spectral characteristics and heat stability (90°C, 5h) of six isolated, structurally related cyanidin-3-O-glycosides from black carrot were investigated in aqueous solutions (pH 3.6 and 4.6) supplemented with chlorogenic acid (molar anthocyanin:co-pigment ratios 1:62.5-1:250). 28946365 3 43 theme triglycosyl 776:786 arg1 moieties 788:795 triglycosyl moieties 776:795 triglycosyl moieties 776:795 The effect significantly decreased when the chain length of the 3-O-linked non-acylated anthocyanins was increased from mono- to di- to triglycosyl moieties, possibly due to steric interferences of bound sugars and co-pigments. 28946365 3 44 theme 3-O-linked 704:713 arg1 anthocyanins 728:739 the 3-O-linked non-acylated anthocyanins 700:739 the 3-O-linked non-acylated anthocyanins 700:739 The effect significantly decreased when the chain length of the 3-O-linked non-acylated anthocyanins was increased from mono- to di- to triglycosyl moieties, possibly due to steric interferences of bound sugars and co-pigments. 28946365 3 45 theme chain 684:688 arg1 length 690:695 the chain length 680:695 the chain length of the 3-O-linked non-acylated anthocyanins 680:739 The effect significantly decreased when the chain length of the 3-O-linked non-acylated anthocyanins was increased from mono- to di- to triglycosyl moieties, possibly due to steric interferences of bound sugars and co-pigments. 28946365 6 46 theme pigment 1161:1167 arg1 stability 1169:1177 thermal pigment stability 1153:1177 thermal pigment stability 1153:1177 Chlorogenic acid addition evoked weak enhancement of thermal pigment stability at pH 3.6, while it was highly detrimental for all anthocyanins at pH 4.6. 28946365 6 47 from pH 1246:1247 arg1 anthocyanins 1230:1241 all anthocyanins 1226:1241 all anthocyanins at pH 4.6 1226:1251 Chlorogenic acid addition evoked weak enhancement of thermal pigment stability at pH 3.6, while it was highly detrimental for all anthocyanins at pH 4.6. 28946365 4 48 theme feruloylated 939:950 arg1 cyanidin-3-O-triglycosides 969:994 feruloylated and sinapoylated cyanidin-3-O-triglycosides 939:994 feruloylated and sinapoylated cyanidin-3-O-triglycosides 939:994 Intermolecular co-pigmentation was investigated for the first time for feruloylated and sinapoylated cyanidin-3-O-triglycosides. 28946365 2 49 from pH 517:518 arg1 % 512:512 up to 97.9 and 122.9% 492:512 up to 97.9 and 122.9% at pH 3.6 492:522 Chlorogenic acid supplementation generally increased absorbance of non-acylated anthocyanins by up to 97.9 and 122.9% at pH 3.6 and 4.6, respectively, being mainly attributed to the formation of intermolecular anthocyanin:co-pigment complexes. 28946365 1 50 theme heat 147:150 arg1 stability 152:160 heat stability 147:160 heat stability 147:160 Spectral characteristics and heat stability (90°C, 5h) of six isolated, structurally related cyanidin-3-O-glycosides from black carrot were investigated in aqueous solutions (pH 3.6 and 4.6) supplemented with chlorogenic acid (molar anthocyanin:co-pigment ratios 1:62.5-1:250). 28946365 3 51 theme steric 814:819 arg1 interferences 821:833 steric interferences 814:833 steric interferences of bound sugars 814:849 The effect significantly decreased when the chain length of the 3-O-linked non-acylated anthocyanins was increased from mono- to di- to triglycosyl moieties, possibly due to steric interferences of bound sugars and co-pigments. 28946365 1 52 theme black 240:244 arg1 carrot 246:251 black carrot 240:251 black carrot 240:251 Spectral characteristics and heat stability (90°C, 5h) of six isolated, structurally related cyanidin-3-O-glycosides from black carrot were investigated in aqueous solutions (pH 3.6 and 4.6) supplemented with chlorogenic acid (molar anthocyanin:co-pigment ratios 1:62.5-1:250). 28946365 2 53 theme acid 408:411 arg1 supplementation 413:427 Chlorogenic acid supplementation 396:427 Chlorogenic acid supplementation 396:427 Chlorogenic acid supplementation generally increased absorbance of non-acylated anthocyanins by up to 97.9 and 122.9% at pH 3.6 and 4.6, respectively, being mainly attributed to the formation of intermolecular anthocyanin:co-pigment complexes. 28946365 1 54 theme chlorogenic 327:337 arg1 1:62.5-1:250 381:392 molar anthocyanin:co-pigment ratios 1:62.5-1:250 345:392 molar anthocyanin:co-pigment ratios 1:62.5-1:250 345:392 Spectral characteristics and heat stability (90°C, 5h) of six isolated, structurally related cyanidin-3-O-glycosides from black carrot were investigated in aqueous solutions (pH 3.6 and 4.6) supplemented with chlorogenic acid (molar anthocyanin:co-pigment ratios 1:62.5-1:250). 28946365 1 54 theme chlorogenic 327:337 arg1 acid 339:342 chlorogenic acid 327:342 chlorogenic acid (molar anthocyanin:co-pigment ratios 1:62.5-1:250) 327:393 Spectral characteristics and heat stability (90°C, 5h) of six isolated, structurally related cyanidin-3-O-glycosides from black carrot were investigated in aqueous solutions (pH 3.6 and 4.6) supplemented with chlorogenic acid (molar anthocyanin:co-pigment ratios 1:62.5-1:250). 28946365 6 55 theme weak 1133:1136 arg1 enhancement 1138:1148 weak enhancement 1133:1148 weak enhancement of thermal pigment stability 1133:1177 Chlorogenic acid addition evoked weak enhancement of thermal pigment stability at pH 3.6, while it was highly detrimental for all anthocyanins at pH 4.6. 28803818 0 0 theme muscular 84:91 arg1 dystrophy 93:101 alpha-dystroglycan-related limb girdle muscular dystrophy 45:101 alpha-dystroglycan-related limb girdle muscular dystrophy 45:101 A homozygous DPM3 mutation in a patient with alpha-dystroglycan-related limb girdle muscular dystrophy. 28803818 4 1 theme essential 702:710 arg1 substrate 718:726 an essential donor substrate 699:726 an essential donor substrate for protein O-mannosyltransferase (POMT) 1 and 2 699:775 Decreased availability of DPM as an essential donor substrate for protein O-mannosyltransferase (POMT) 1 and 2 explains defective skeletal muscle alpha-dystroglycan O-glycosylation. 28803818 1 2 theme wide 168:171 arg1 spectrum 173:180 a wide spectrum 166:180 a wide spectrum of muscular dystrophies ranging from severe congenital muscular dystrophy associated with abnormal brain and eye development to mild limb girdle muscular dystrophy 166:344 Defects of O-linked glycosylation of alpha-dystroglycan cause a wide spectrum of muscular dystrophies ranging from severe congenital muscular dystrophy associated with abnormal brain and eye development to mild limb girdle muscular dystrophy. 28803818 0 3 theme girdle 77:82 arg1 dystrophy 93:101 alpha-dystroglycan-related limb girdle muscular dystrophy 45:101 alpha-dystroglycan-related limb girdle muscular dystrophy 45:101 A homozygous DPM3 mutation in a patient with alpha-dystroglycan-related limb girdle muscular dystrophy. 28803818 5 4 theme mild 914:917 arg1 phenotype 950:958 an isolated and mild limb girdle muscular dystrophy phenotype 898:958 an isolated and mild limb girdle muscular dystrophy phenotype without cardiomyopathy 898:981 Our findings show that DPM3 mutations may lead to an isolated and mild limb girdle muscular dystrophy phenotype without cardiomyopathy. 28803818 5 5 theme limb 919:922 arg1 phenotype 950:958 an isolated and mild limb girdle muscular dystrophy phenotype 898:958 an isolated and mild limb girdle muscular dystrophy phenotype without cardiomyopathy 898:981 Our findings show that DPM3 mutations may lead to an isolated and mild limb girdle muscular dystrophy phenotype without cardiomyopathy. 28803818 3 6 theme Exome 476:480 arg1 sequencing 482:491 Exome sequencing 476:491 Exome sequencing 476:491 Exome sequencing uncovered a homozygous c.131T > G (p.Leu44Pro) substitution in DPM3, encoding dolichol-P-mannose (DPM) synthase subunit 3, leading to a 50% reduction of enzymatic activity. 28803818 4 7 theme defective 786:794 arg1 alpha-dystroglycan 812:829 defective skeletal muscle alpha-dystroglycan 786:829 defective skeletal muscle alpha-dystroglycan O-glycosylation 786:845 Decreased availability of DPM as an essential donor substrate for protein O-mannosyltransferase (POMT) 1 and 2 explains defective skeletal muscle alpha-dystroglycan O-glycosylation. 28803818 4 8 theme O-mannosyltransferase 740:760 arg1 POMT 763:766 protein O-mannosyltransferase (POMT) 1 and 2 732:775 POMT 763:766 Decreased availability of DPM as an essential donor substrate for protein O-mannosyltransferase (POMT) 1 and 2 explains defective skeletal muscle alpha-dystroglycan O-glycosylation. 28803818 1 9 theme eye 291:293 arg1 development 295:305 abnormal brain and eye development 272:305 development 295:305 Defects of O-linked glycosylation of alpha-dystroglycan cause a wide spectrum of muscular dystrophies ranging from severe congenital muscular dystrophy associated with abnormal brain and eye development to mild limb girdle muscular dystrophy. 28803818 3 10 theme dolichol-P-mannose 571:588 arg1 synthase 596:603 dolichol-P-mannose (DPM) synthase 571:603 dolichol-P-mannose (DPM) synthase subunit 3 571:613 Exome sequencing uncovered a homozygous c.131T > G (p.Leu44Pro) substitution in DPM3, encoding dolichol-P-mannose (DPM) synthase subunit 3, leading to a 50% reduction of enzymatic activity. 28803818 3 11 from substitution 540:551 arg1 DPM3 556:559 DPM3 556:559 DPM3 556:559 Exome sequencing uncovered a homozygous c.131T > G (p.Leu44Pro) substitution in DPM3, encoding dolichol-P-mannose (DPM) synthase subunit 3, leading to a 50% reduction of enzymatic activity. 28803818 3 12 theme p.Leu44Pro 528:537 arg1 substitution 540:551 a homozygous c.131T > G (p.Leu44Pro) substitution 503:551 a homozygous c.131T > G (p.Leu44Pro) substitution 503:551 Exome sequencing uncovered a homozygous c.131T > G (p.Leu44Pro) substitution in DPM3, encoding dolichol-P-mannose (DPM) synthase subunit 3, leading to a 50% reduction of enzymatic activity. 28803818 3 13 theme homozygous 505:514 arg1 substitution 540:551 a homozygous c.131T > G (p.Leu44Pro) substitution 503:551 a homozygous c.131T > G (p.Leu44Pro) substitution 503:551 Exome sequencing uncovered a homozygous c.131T > G (p.Leu44Pro) substitution in DPM3, encoding dolichol-P-mannose (DPM) synthase subunit 3, leading to a 50% reduction of enzymatic activity. 28803818 3 14 theme c.131T > G 516:525 arg1 substitution 540:551 a homozygous c.131T > G (p.Leu44Pro) substitution 503:551 a homozygous c.131T > G (p.Leu44Pro) substitution 503:551 Exome sequencing uncovered a homozygous c.131T > G (p.Leu44Pro) substitution in DPM3, encoding dolichol-P-mannose (DPM) synthase subunit 3, leading to a 50% reduction of enzymatic activity. 28803818 2 15 theme muscle 411:416 arg1 weakness 418:425 isolated pelvic girdle muscle weakness 388:425 isolated pelvic girdle muscle weakness 388:425 We report a female patient who developed isolated pelvic girdle muscle weakness and wasting, which became symptomatic at age 42. 28803818 4 16 theme Decreased 666:674 arg1 availability 676:687 Decreased availability 666:687 Decreased availability of DPM as an essential donor substrate for protein O-mannosyltransferase (POMT) 1 and 2 666:775 Decreased availability of DPM as an essential donor substrate for protein O-mannosyltransferase (POMT) 1 and 2 explains defective skeletal muscle alpha-dystroglycan O-glycosylation. 28803818 1 17 theme muscular 185:192 arg1 dystrophies 194:204 muscular dystrophies 185:204 muscular dystrophies ranging from severe congenital muscular dystrophy associated with abnormal brain and eye development to mild limb girdle muscular dystrophy 185:344 Defects of O-linked glycosylation of alpha-dystroglycan cause a wide spectrum of muscular dystrophies ranging from severe congenital muscular dystrophy associated with abnormal brain and eye development to mild limb girdle muscular dystrophy. 28803818 0 18 theme homozygous 2:11 arg1 mutation 18:25 A homozygous DPM3 mutation 0:25 A homozygous DPM3 mutation in a patient with alpha-dystroglycan-related limb girdle muscular dystrophy 0:101 A homozygous DPM3 mutation in a patient with alpha-dystroglycan-related limb girdle muscular dystrophy. 28803818 1 19 theme dystrophies 194:204 arg1 spectrum 173:180 a wide spectrum 166:180 a wide spectrum of muscular dystrophies ranging from severe congenital muscular dystrophy associated with abnormal brain and eye development to mild limb girdle muscular dystrophy 166:344 Defects of O-linked glycosylation of alpha-dystroglycan cause a wide spectrum of muscular dystrophies ranging from severe congenital muscular dystrophy associated with abnormal brain and eye development to mild limb girdle muscular dystrophy. 28803818 3 20 theme synthase 596:603 arg1 subunit 605:611 dolichol-P-mannose (DPM) synthase subunit 3 571:613 dolichol-P-mannose (DPM) synthase subunit 3 571:613 Exome sequencing uncovered a homozygous c.131T > G (p.Leu44Pro) substitution in DPM3, encoding dolichol-P-mannose (DPM) synthase subunit 3, leading to a 50% reduction of enzymatic activity. 28803818 2 21 theme girdle 404:409 arg1 weakness 418:425 isolated pelvic girdle muscle weakness 388:425 isolated pelvic girdle muscle weakness 388:425 We report a female patient who developed isolated pelvic girdle muscle weakness and wasting, which became symptomatic at age 42. 28803818 5 22 theme DPM3 871:874 arg1 mutations 876:884 DPM3 mutations 871:884 DPM3 mutations 871:884 Our findings show that DPM3 mutations may lead to an isolated and mild limb girdle muscular dystrophy phenotype without cardiomyopathy. 28803818 1 23 theme mild 310:313 arg1 dystrophy 336:344 mild limb girdle muscular dystrophy 310:344 mild limb girdle muscular dystrophy 310:344 Defects of O-linked glycosylation of alpha-dystroglycan cause a wide spectrum of muscular dystrophies ranging from severe congenital muscular dystrophy associated with abnormal brain and eye development to mild limb girdle muscular dystrophy. 28803818 1 24 gly glycosylation 124:136 arg1 alpha-dystroglycan 141:158 alpha-dystroglycan 141:158 alpha-dystroglycan 141:158 Defects of O-linked glycosylation of alpha-dystroglycan cause a wide spectrum of muscular dystrophies ranging from severe congenital muscular dystrophy associated with abnormal brain and eye development to mild limb girdle muscular dystrophy. 28803818 0 25 theme DPM3 13:16 arg1 mutation 18:25 A homozygous DPM3 mutation 0:25 A homozygous DPM3 mutation in a patient with alpha-dystroglycan-related limb girdle muscular dystrophy 0:101 A homozygous DPM3 mutation in a patient with alpha-dystroglycan-related limb girdle muscular dystrophy. 28803818 1 26 theme limb 315:318 arg1 dystrophy 336:344 mild limb girdle muscular dystrophy 310:344 mild limb girdle muscular dystrophy 310:344 Defects of O-linked glycosylation of alpha-dystroglycan cause a wide spectrum of muscular dystrophies ranging from severe congenital muscular dystrophy associated with abnormal brain and eye development to mild limb girdle muscular dystrophy. 28803818 3 27 theme enzymatic 646:654 arg1 activity 656:663 enzymatic activity 646:663 enzymatic activity 646:663 Exome sequencing uncovered a homozygous c.131T > G (p.Leu44Pro) substitution in DPM3, encoding dolichol-P-mannose (DPM) synthase subunit 3, leading to a 50% reduction of enzymatic activity. 28803818 3 28 theme DPM 591:593 arg1 synthase 596:603 dolichol-P-mannose (DPM) synthase 571:603 dolichol-P-mannose (DPM) synthase subunit 3 571:613 Exome sequencing uncovered a homozygous c.131T > G (p.Leu44Pro) substitution in DPM3, encoding dolichol-P-mannose (DPM) synthase subunit 3, leading to a 50% reduction of enzymatic activity. 28803818 1 29 theme severe 219:224 arg1 dystrophy 246:254 severe congenital muscular dystrophy 219:254 severe congenital muscular dystrophy associated with abnormal brain and eye development 219:305 Defects of O-linked glycosylation of alpha-dystroglycan cause a wide spectrum of muscular dystrophies ranging from severe congenital muscular dystrophy associated with abnormal brain and eye development to mild limb girdle muscular dystrophy. 28803818 1 30 theme girdle 320:325 arg1 dystrophy 336:344 mild limb girdle muscular dystrophy 310:344 mild limb girdle muscular dystrophy 310:344 Defects of O-linked glycosylation of alpha-dystroglycan cause a wide spectrum of muscular dystrophies ranging from severe congenital muscular dystrophy associated with abnormal brain and eye development to mild limb girdle muscular dystrophy. 28803818 3 31 theme activity 656:663 arg1 reduction 633:641 a 50% reduction 627:641 a 50% reduction of enzymatic activity 627:663 Exome sequencing uncovered a homozygous c.131T > G (p.Leu44Pro) substitution in DPM3, encoding dolichol-P-mannose (DPM) synthase subunit 3, leading to a 50% reduction of enzymatic activity. 28803818 1 32 theme congenital 226:235 arg1 dystrophy 246:254 severe congenital muscular dystrophy 219:254 severe congenital muscular dystrophy associated with abnormal brain and eye development 219:305 Defects of O-linked glycosylation of alpha-dystroglycan cause a wide spectrum of muscular dystrophies ranging from severe congenital muscular dystrophy associated with abnormal brain and eye development to mild limb girdle muscular dystrophy. 28803818 1 33 theme muscular 327:334 arg1 dystrophy 336:344 mild limb girdle muscular dystrophy 310:344 mild limb girdle muscular dystrophy 310:344 Defects of O-linked glycosylation of alpha-dystroglycan cause a wide spectrum of muscular dystrophies ranging from severe congenital muscular dystrophy associated with abnormal brain and eye development to mild limb girdle muscular dystrophy. 28803818 4 34 theme donor 712:716 arg1 substrate 718:726 an essential donor substrate 699:726 an essential donor substrate for protein O-mannosyltransferase (POMT) 1 and 2 699:775 Decreased availability of DPM as an essential donor substrate for protein O-mannosyltransferase (POMT) 1 and 2 explains defective skeletal muscle alpha-dystroglycan O-glycosylation. 28803818 5 35 theme muscular 931:938 arg1 phenotype 950:958 an isolated and mild limb girdle muscular dystrophy phenotype 898:958 an isolated and mild limb girdle muscular dystrophy phenotype without cardiomyopathy 898:981 Our findings show that DPM3 mutations may lead to an isolated and mild limb girdle muscular dystrophy phenotype without cardiomyopathy. 28803818 1 36 theme muscular 237:244 arg1 dystrophy 246:254 severe congenital muscular dystrophy 219:254 severe congenital muscular dystrophy associated with abnormal brain and eye development 219:305 Defects of O-linked glycosylation of alpha-dystroglycan cause a wide spectrum of muscular dystrophies ranging from severe congenital muscular dystrophy associated with abnormal brain and eye development to mild limb girdle muscular dystrophy. 28803818 5 37 theme isolated 901:908 arg1 phenotype 950:958 an isolated and mild limb girdle muscular dystrophy phenotype 898:958 an isolated and mild limb girdle muscular dystrophy phenotype without cardiomyopathy 898:981 Our findings show that DPM3 mutations may lead to an isolated and mild limb girdle muscular dystrophy phenotype without cardiomyopathy. 28803818 1 38 theme O-linked 115:122 arg1 glycosylation 124:136 O-linked glycosylation 115:136 O-linked glycosylation of alpha-dystroglycan 115:158 Defects of O-linked glycosylation of alpha-dystroglycan cause a wide spectrum of muscular dystrophies ranging from severe congenital muscular dystrophy associated with abnormal brain and eye development to mild limb girdle muscular dystrophy. 28803818 1 39 theme glycosylation 124:136 arg1 Defects 104:110 Defects 104:110 Defects of O-linked glycosylation of alpha-dystroglycan 104:158 Defects of O-linked glycosylation of alpha-dystroglycan cause a wide spectrum of muscular dystrophies ranging from severe congenital muscular dystrophy associated with abnormal brain and eye development to mild limb girdle muscular dystrophy. 28803818 1 40 link O-linked 115:122 arg1 glycosylation 124:136 O-linked glycosylation 115:136 O-linked glycosylation of alpha-dystroglycan 115:158 Defects of O-linked glycosylation of alpha-dystroglycan cause a wide spectrum of muscular dystrophies ranging from severe congenital muscular dystrophy associated with abnormal brain and eye development to mild limb girdle muscular dystrophy. 28803818 4 41 theme skeletal 796:803 arg1 alpha-dystroglycan 812:829 defective skeletal muscle alpha-dystroglycan 786:829 defective skeletal muscle alpha-dystroglycan O-glycosylation 786:845 Decreased availability of DPM as an essential donor substrate for protein O-mannosyltransferase (POMT) 1 and 2 explains defective skeletal muscle alpha-dystroglycan O-glycosylation. 28803818 3 42 theme 50 629:630 arg1 % 631:631 % 631:631 % 631:631 Exome sequencing uncovered a homozygous c.131T > G (p.Leu44Pro) substitution in DPM3, encoding dolichol-P-mannose (DPM) synthase subunit 3, leading to a 50% reduction of enzymatic activity. 28803818 4 43 theme DPM 692:694 arg1 availability 676:687 Decreased availability 666:687 Decreased availability of DPM as an essential donor substrate for protein O-mannosyltransferase (POMT) 1 and 2 666:775 Decreased availability of DPM as an essential donor substrate for protein O-mannosyltransferase (POMT) 1 and 2 explains defective skeletal muscle alpha-dystroglycan O-glycosylation. 28803818 4 44 theme protein 732:738 arg1 POMT 763:766 protein O-mannosyltransferase (POMT) 1 and 2 732:775 POMT 763:766 Decreased availability of DPM as an essential donor substrate for protein O-mannosyltransferase (POMT) 1 and 2 explains defective skeletal muscle alpha-dystroglycan O-glycosylation. 28803818 5 45 theme girdle 924:929 arg1 phenotype 950:958 an isolated and mild limb girdle muscular dystrophy phenotype 898:958 an isolated and mild limb girdle muscular dystrophy phenotype without cardiomyopathy 898:981 Our findings show that DPM3 mutations may lead to an isolated and mild limb girdle muscular dystrophy phenotype without cardiomyopathy. 28803818 3 46 theme % 631:631 arg1 reduction 633:641 a 50% reduction 627:641 a 50% reduction of enzymatic activity 627:663 Exome sequencing uncovered a homozygous c.131T > G (p.Leu44Pro) substitution in DPM3, encoding dolichol-P-mannose (DPM) synthase subunit 3, leading to a 50% reduction of enzymatic activity. 28803818 1 47 theme alpha-dystroglycan 141:158 arg1 glycosylation 124:136 O-linked glycosylation 115:136 O-linked glycosylation of alpha-dystroglycan 115:158 Defects of O-linked glycosylation of alpha-dystroglycan cause a wide spectrum of muscular dystrophies ranging from severe congenital muscular dystrophy associated with abnormal brain and eye development to mild limb girdle muscular dystrophy. 28803818 5 48 theme dystrophy 940:948 arg1 phenotype 950:958 an isolated and mild limb girdle muscular dystrophy phenotype 898:958 an isolated and mild limb girdle muscular dystrophy phenotype without cardiomyopathy 898:981 Our findings show that DPM3 mutations may lead to an isolated and mild limb girdle muscular dystrophy phenotype without cardiomyopathy. 28803818 0 49 theme limb 72:75 arg1 dystrophy 93:101 alpha-dystroglycan-related limb girdle muscular dystrophy 45:101 alpha-dystroglycan-related limb girdle muscular dystrophy 45:101 A homozygous DPM3 mutation in a patient with alpha-dystroglycan-related limb girdle muscular dystrophy. 28803818 2 50 theme female 359:364 arg1 patient 366:372 a female patient 357:372 a female patient who developed isolated pelvic girdle muscle weakness and wasting, which became symptomatic at age 42 357:473 We report a female patient who developed isolated pelvic girdle muscle weakness and wasting, which became symptomatic at age 42. 28803818 4 51 theme alpha-dystroglycan 812:829 arg1 O-glycosylation 831:845 defective skeletal muscle alpha-dystroglycan O-glycosylation 786:845 defective skeletal muscle alpha-dystroglycan O-glycosylation 786:845 Decreased availability of DPM as an essential donor substrate for protein O-mannosyltransferase (POMT) 1 and 2 explains defective skeletal muscle alpha-dystroglycan O-glycosylation. 28803818 0 52 with patient 32:38 arg1 dystrophy 93:101 alpha-dystroglycan-related limb girdle muscular dystrophy 45:101 alpha-dystroglycan-related limb girdle muscular dystrophy 45:101 A homozygous DPM3 mutation in a patient with alpha-dystroglycan-related limb girdle muscular dystrophy. 28803818 2 53 theme pelvic 397:402 arg1 weakness 418:425 isolated pelvic girdle muscle weakness 388:425 isolated pelvic girdle muscle weakness 388:425 We report a female patient who developed isolated pelvic girdle muscle weakness and wasting, which became symptomatic at age 42. 28803818 0 54 theme alpha-dystroglycan-related 45:70 arg1 dystrophy 93:101 alpha-dystroglycan-related limb girdle muscular dystrophy 45:101 alpha-dystroglycan-related limb girdle muscular dystrophy 45:101 A homozygous DPM3 mutation in a patient with alpha-dystroglycan-related limb girdle muscular dystrophy. 28803818 0 55 from mutation 18:25 arg1 patient 32:38 a patient 30:38 a patient with alpha-dystroglycan-related limb girdle muscular dystrophy 30:101 A homozygous DPM3 mutation in a patient with alpha-dystroglycan-related limb girdle muscular dystrophy. 28803818 4 56 theme muscle 805:810 arg1 alpha-dystroglycan 812:829 defective skeletal muscle alpha-dystroglycan 786:829 defective skeletal muscle alpha-dystroglycan O-glycosylation 786:845 Decreased availability of DPM as an essential donor substrate for protein O-mannosyltransferase (POMT) 1 and 2 explains defective skeletal muscle alpha-dystroglycan O-glycosylation. 28803818 2 57 theme isolated 388:395 arg1 weakness 418:425 isolated pelvic girdle muscle weakness 388:425 isolated pelvic girdle muscle weakness 388:425 We report a female patient who developed isolated pelvic girdle muscle weakness and wasting, which became symptomatic at age 42. 28803818 1 58 theme abnormal 272:279 arg1 brain 281:285 abnormal brain and eye development 272:305 brain 281:285 Defects of O-linked glycosylation of alpha-dystroglycan cause a wide spectrum of muscular dystrophies ranging from severe congenital muscular dystrophy associated with abnormal brain and eye development to mild limb girdle muscular dystrophy. 28681591 8 0 theme oncogenes 1177:1185 arg1 expression 1139:1148 lower expression 1133:1148 lower expression of Ki-67 and HPV E6 and E7 oncogenes 1133:1185 Lung tissues from mice engrafted with OGT-knockdown HeLa cells (shOGT) exhibited lower expression of Ki-67 and HPV E6 and E7 oncogenes compared to lung tissues from mice engrafted with control HeLa cells (shCTL). 28681591 4 1 theme O-GlcNAcylation 504:518 arg1 levels 444:449 elevated levels 435:449 elevated levels of O-linked-N-actylglucosamine transferase (OGT) and O-GlcNAcylation in cervical cancer cells 435:543 We found elevated levels of O-linked-N-actylglucosamine transferase (OGT) and O-GlcNAcylation in cervical cancer cells compared to those in non-malignant epithelial cells and detected increased expression of NF-κB p65 (p65) and CXCR4 in cervical cancer cells. 28681591 8 2 theme Lung 1052:1055 arg1 tissues 1057:1063 Lung tissues 1052:1063 Lung tissues from mice engrafted with OGT-knockdown HeLa cells (shOGT) 1052:1121 Lung tissues from mice engrafted with OGT-knockdown HeLa cells (shOGT) exhibited lower expression of Ki-67 and HPV E6 and E7 oncogenes compared to lung tissues from mice engrafted with control HeLa cells (shCTL). 28681591 0 3 theme NF-κB 19:23 arg1 O-GlcNAcylation 0:14 O-GlcNAcylation 0:14 O-GlcNAcylation of NF-κB 0:23 O-GlcNAcylation of NF-κB Promotes Lung Metastasis of Cervical Cancer Cells via Upregulation of CXCR4 Expression. 28681591 5 4 theme HeLa 781:784 arg1 cells 786:790 HeLa cells 781:790 HeLa cells 781:790 Knockdown of OGT inhibited the O-GlcNAcylation of p65 and decreased CXCR4 expression levels in HeLa cells. 28681591 4 5 theme cancer 532:537 arg1 cells 539:543 cervical cancer cells 523:543 cervical cancer cells 523:543 We found elevated levels of O-linked-N-actylglucosamine transferase (OGT) and O-GlcNAcylation in cervical cancer cells compared to those in non-malignant epithelial cells and detected increased expression of NF-κB p65 (p65) and CXCR4 in cervical cancer cells. 28681591 4 6 theme elevated 435:442 arg1 levels 444:449 elevated levels 435:449 elevated levels of O-linked-N-actylglucosamine transferase (OGT) and O-GlcNAcylation in cervical cancer cells 435:543 We found elevated levels of O-linked-N-actylglucosamine transferase (OGT) and O-GlcNAcylation in cervical cancer cells compared to those in non-malignant epithelial cells and detected increased expression of NF-κB p65 (p65) and CXCR4 in cervical cancer cells. 28681591 4 7 theme O-linked-N-actylglucosamine 454:480 arg1 OGT 495:497 OGT 495:497 OGT 495:497 We found elevated levels of O-linked-N-actylglucosamine transferase (OGT) and O-GlcNAcylation in cervical cancer cells compared to those in non-malignant epithelial cells and detected increased expression of NF-κB p65 (p65) and CXCR4 in cervical cancer cells. 28681591 4 7 theme O-linked-N-actylglucosamine 454:480 arg1 transferase 482:492 O-linked-N-actylglucosamine transferase 454:492 O-linked-N-actylglucosamine transferase (OGT) 454:498 We found elevated levels of O-linked-N-actylglucosamine transferase (OGT) and O-GlcNAcylation in cervical cancer cells compared to those in non-malignant epithelial cells and detected increased expression of NF-κB p65 (p65) and CXCR4 in cervical cancer cells. 28681591 6 8 theme expression 877:886 arg1 levels 888:893 CXCR4 expression levels 871:893 CXCR4 expression levels 871:893 Thiamet G treatment increased O-GlcNAcylated p65, which subsequently enhanced CXCR4 expression levels. 28681591 0 9 theme CXCR4 95:99 arg1 Expression 101:110 CXCR4 Expression 95:110 CXCR4 Expression 95:110 O-GlcNAcylation of NF-κB Promotes Lung Metastasis of Cervical Cancer Cells via Upregulation of CXCR4 Expression. 28681591 4 10 theme cervical 523:530 arg1 cells 539:543 cervical cancer cells 523:543 cervical cancer cells 523:543 We found elevated levels of O-linked-N-actylglucosamine transferase (OGT) and O-GlcNAcylation in cervical cancer cells compared to those in non-malignant epithelial cells and detected increased expression of NF-κB p65 (p65) and CXCR4 in cervical cancer cells. 28681591 8 11 theme OGT-knockdown 1090:1102 arg1 cells 1109:1113 OGT-knockdown HeLa cells 1090:1113 OGT-knockdown HeLa cells (shOGT) 1090:1121 Lung tissues from mice engrafted with OGT-knockdown HeLa cells (shOGT) exhibited lower expression of Ki-67 and HPV E6 and E7 oncogenes compared to lung tissues from mice engrafted with control HeLa cells (shCTL). 28681591 8 11 theme OGT-knockdown 1090:1102 arg1 shOGT 1116:1120 shOGT 1116:1120 shOGT 1116:1120 Lung tissues from mice engrafted with OGT-knockdown HeLa cells (shOGT) exhibited lower expression of Ki-67 and HPV E6 and E7 oncogenes compared to lung tissues from mice engrafted with control HeLa cells (shCTL). 28681591 6 12 theme O-GlcNAcylated 823:836 arg1 p65 838:840 O-GlcNAcylated p65 823:840 O-GlcNAcylated p65 823:840 Thiamet G treatment increased O-GlcNAcylated p65, which subsequently enhanced CXCR4 expression levels. 28681591 4 13 theme cervical 663:670 arg1 cells 679:683 cervical cancer cells 663:683 cervical cancer cells 663:683 We found elevated levels of O-linked-N-actylglucosamine transferase (OGT) and O-GlcNAcylation in cervical cancer cells compared to those in non-malignant epithelial cells and detected increased expression of NF-κB p65 (p65) and CXCR4 in cervical cancer cells. 28681591 5 14 theme CXCR4 754:758 arg1 levels 771:776 CXCR4 expression levels 754:776 CXCR4 expression levels in HeLa cells 754:790 Knockdown of OGT inhibited the O-GlcNAcylation of p65 and decreased CXCR4 expression levels in HeLa cells. 28681591 9 15 theme shOGT 1316:1320 arg1 cells 1322:1326 shOGT cells 1316:1326 shOGT cells 1316:1326 In addition, lung tissues from mice engrafted with shOGT cells exhibited lower p65 and CXCR4 immunoreactivity compared to tissues from mice engrafted with shCTL cells. 28681591 9 16 theme p65 1344:1346 arg1 immunoreactivity 1358:1373 lower p65 and CXCR4 immunoreactivity 1338:1373 lower p65 and CXCR4 immunoreactivity 1338:1373 In addition, lung tissues from mice engrafted with shOGT cells exhibited lower p65 and CXCR4 immunoreactivity compared to tissues from mice engrafted with shCTL cells. 28681591 2 17 theme transcriptional 276:290 arg1 activity 292:299 its transcriptional activity 272:299 its transcriptional activity 272:299 NF-κB regulates CXCR4 expression in cancer cells, and O-GlcNAc modification of NF-κB promotes its transcriptional activity. 28681591 4 18 theme increased 610:618 arg1 expression 620:629 increased expression 610:629 increased expression of NF-κB p65 (p65) and CXCR4 610:658 We found elevated levels of O-linked-N-actylglucosamine transferase (OGT) and O-GlcNAcylation in cervical cancer cells compared to those in non-malignant epithelial cells and detected increased expression of NF-κB p65 (p65) and CXCR4 in cervical cancer cells. 28681591 8 19 theme E6 1167:1168 arg1 expression 1139:1148 lower expression 1133:1148 lower expression of Ki-67 and HPV E6 and E7 oncogenes 1133:1185 Lung tissues from mice engrafted with OGT-knockdown HeLa cells (shOGT) exhibited lower expression of Ki-67 and HPV E6 and E7 oncogenes compared to lung tissues from mice engrafted with control HeLa cells (shCTL). 28681591 10 20 theme lung 1500:1503 arg1 metastasis 1505:1514 lung metastasis 1500:1514 lung metastasis of cervical cancer cells 1500:1539 Taken together, our data suggest that p65 O-GlcNAcylation promotes lung metastasis of cervical cancer cells by activating CXCR4 expression. 28681591 10 21 theme cancer 1528:1533 arg1 cells 1535:1539 cervical cancer cells 1519:1539 cervical cancer cells 1519:1539 Taken together, our data suggest that p65 O-GlcNAcylation promotes lung metastasis of cervical cancer cells by activating CXCR4 expression. 28681591 1 22 theme cancer 159:164 arg1 metastasis 166:175 cancer metastasis 159:175 cancer metastasis 159:175 C-X-C chemokine receptor 4 (CXCR4) stimulates cancer metastasis. 28681591 0 23 theme Expression 101:110 arg1 Upregulation 79:90 Upregulation 79:90 Upregulation of CXCR4 Expression 79:110 O-GlcNAcylation of NF-κB Promotes Lung Metastasis of Cervical Cancer Cells via Upregulation of CXCR4 Expression. 28681591 6 24 theme Thiamet 793:799 arg1 treatment 803:811 Thiamet G treatment 793:811 Thiamet G treatment 793:811 Thiamet G treatment increased O-GlcNAcylated p65, which subsequently enhanced CXCR4 expression levels. 28681591 6 25 theme G 801:801 arg1 treatment 803:811 Thiamet G treatment 793:811 Thiamet G treatment 793:811 Thiamet G treatment increased O-GlcNAcylated p65, which subsequently enhanced CXCR4 expression levels. 28681591 9 26 theme lung 1278:1281 arg1 tissues 1283:1289 lung tissues 1278:1289 lung tissues from mice engrafted with shOGT cells 1278:1326 In addition, lung tissues from mice engrafted with shOGT cells exhibited lower p65 and CXCR4 immunoreactivity compared to tissues from mice engrafted with shCTL cells. 28681591 8 27 theme E7 1174:1175 arg1 oncogenes 1177:1185 Ki-67 and HPV E6 and E7 oncogenes 1153:1185 oncogenes 1177:1185 Lung tissues from mice engrafted with OGT-knockdown HeLa cells (shOGT) exhibited lower expression of Ki-67 and HPV E6 and E7 oncogenes compared to lung tissues from mice engrafted with control HeLa cells (shCTL). 28681591 10 28 theme p65 1471:1473 arg1 O-GlcNAcylation 1475:1489 p65 O-GlcNAcylation 1471:1489 p65 O-GlcNAcylation 1471:1489 Taken together, our data suggest that p65 O-GlcNAcylation promotes lung metastasis of cervical cancer cells by activating CXCR4 expression. 28681591 0 29 theme Cells 69:73 arg1 Metastasis 39:48 Lung Metastasis 34:48 Lung Metastasis of Cervical Cancer Cells 34:73 O-GlcNAcylation of NF-κB Promotes Lung Metastasis of Cervical Cancer Cells via Upregulation of CXCR4 Expression. 28681591 3 30 theme lung 390:393 arg1 metastasis 395:404 lung metastasis 390:404 lung metastasis of cervical cancer 390:423 Here, we determined whether CXCR4 expression is affected by O-GlcNAcylation of NF-κB in lung metastasis of cervical cancer. 28681591 4 31 theme non-malignant 566:578 arg1 cells 591:595 non-malignant epithelial cells 566:595 non-malignant epithelial cells 566:595 We found elevated levels of O-linked-N-actylglucosamine transferase (OGT) and O-GlcNAcylation in cervical cancer cells compared to those in non-malignant epithelial cells and detected increased expression of NF-κB p65 (p65) and CXCR4 in cervical cancer cells. 28681591 4 32 theme cancer 672:677 arg1 cells 679:683 cervical cancer cells 663:683 cervical cancer cells 663:683 We found elevated levels of O-linked-N-actylglucosamine transferase (OGT) and O-GlcNAcylation in cervical cancer cells compared to those in non-malignant epithelial cells and detected increased expression of NF-κB p65 (p65) and CXCR4 in cervical cancer cells. 28681591 8 33 theme lower 1133:1137 arg1 expression 1139:1148 lower expression 1133:1148 lower expression of Ki-67 and HPV E6 and E7 oncogenes 1133:1185 Lung tissues from mice engrafted with OGT-knockdown HeLa cells (shOGT) exhibited lower expression of Ki-67 and HPV E6 and E7 oncogenes compared to lung tissues from mice engrafted with control HeLa cells (shCTL). 28681591 8 34 theme lung 1199:1202 arg1 tissues 1204:1210 lung tissues 1199:1210 lung tissues from mice engrafted with control HeLa cells (shCTL) 1199:1262 Lung tissues from mice engrafted with OGT-knockdown HeLa cells (shOGT) exhibited lower expression of Ki-67 and HPV E6 and E7 oncogenes compared to lung tissues from mice engrafted with control HeLa cells (shCTL). 28681591 10 35 theme cervical 1519:1526 arg1 cells 1535:1539 cervical cancer cells 1519:1539 cervical cancer cells 1519:1539 Taken together, our data suggest that p65 O-GlcNAcylation promotes lung metastasis of cervical cancer cells by activating CXCR4 expression. 28681591 8 36 theme HeLa 1245:1248 arg1 shCTL 1257:1261 shCTL 1257:1261 shCTL 1257:1261 Lung tissues from mice engrafted with OGT-knockdown HeLa cells (shOGT) exhibited lower expression of Ki-67 and HPV E6 and E7 oncogenes compared to lung tissues from mice engrafted with control HeLa cells (shCTL). 28681591 8 36 theme HeLa 1245:1248 arg1 cells 1250:1254 control HeLa cells 1237:1254 control HeLa cells (shCTL) 1237:1262 Lung tissues from mice engrafted with OGT-knockdown HeLa cells (shOGT) exhibited lower expression of Ki-67 and HPV E6 and E7 oncogenes compared to lung tissues from mice engrafted with control HeLa cells (shCTL). 28681591 3 37 theme NF-κB 381:385 arg1 O-GlcNAcylation 362:376 O-GlcNAcylation 362:376 O-GlcNAcylation of NF-κB in lung metastasis of cervical cancer 362:423 Here, we determined whether CXCR4 expression is affected by O-GlcNAcylation of NF-κB in lung metastasis of cervical cancer. 28681591 9 38 theme CXCR4 1352:1356 arg1 immunoreactivity 1358:1373 lower p65 and CXCR4 immunoreactivity 1338:1373 lower p65 and CXCR4 immunoreactivity 1338:1373 In addition, lung tissues from mice engrafted with shOGT cells exhibited lower p65 and CXCR4 immunoreactivity compared to tissues from mice engrafted with shCTL cells. 28681591 7 39 from expression 1026:1035 arg1 cells 1045:1049 HeLa cells 1040:1049 HeLa cells 1040:1049 Inhibition of O-GlcNAcylation by 6-Diazo-5-oxo-L-norleucine (DON) treatment decreased p65 activation, eventually inhibiting CXCR4 expression in HeLa cells. 28681591 3 40 theme cervical 409:416 arg1 cancer 418:423 cervical cancer 409:423 cervical cancer 409:423 Here, we determined whether CXCR4 expression is affected by O-GlcNAcylation of NF-κB in lung metastasis of cervical cancer. 28681591 4 41 theme epithelial 580:589 arg1 cells 591:595 non-malignant epithelial cells 566:595 non-malignant epithelial cells 566:595 We found elevated levels of O-linked-N-actylglucosamine transferase (OGT) and O-GlcNAcylation in cervical cancer cells compared to those in non-malignant epithelial cells and detected increased expression of NF-κB p65 (p65) and CXCR4 in cervical cancer cells. 28681591 5 42 theme expression 760:769 arg1 levels 771:776 CXCR4 expression levels 754:776 CXCR4 expression levels in HeLa cells 754:790 Knockdown of OGT inhibited the O-GlcNAcylation of p65 and decreased CXCR4 expression levels in HeLa cells. 28681591 4 43 theme CXCR4 654:658 arg1 expression 620:629 increased expression 610:629 increased expression of NF-κB p65 (p65) and CXCR4 610:658 We found elevated levels of O-linked-N-actylglucosamine transferase (OGT) and O-GlcNAcylation in cervical cancer cells compared to those in non-malignant epithelial cells and detected increased expression of NF-κB p65 (p65) and CXCR4 in cervical cancer cells. 28681591 0 44 theme Lung 34:37 arg1 Metastasis 39:48 Lung Metastasis 34:48 Lung Metastasis of Cervical Cancer Cells 34:73 O-GlcNAcylation of NF-κB Promotes Lung Metastasis of Cervical Cancer Cells via Upregulation of CXCR4 Expression. 28681591 8 45 from mice 1070:1073 arg1 tissues 1057:1063 Lung tissues 1052:1063 Lung tissues from mice engrafted with OGT-knockdown HeLa cells (shOGT) 1052:1121 Lung tissues from mice engrafted with OGT-knockdown HeLa cells (shOGT) exhibited lower expression of Ki-67 and HPV E6 and E7 oncogenes compared to lung tissues from mice engrafted with control HeLa cells (shCTL). 28681591 3 46 theme cancer 418:423 arg1 metastasis 395:404 lung metastasis 390:404 lung metastasis of cervical cancer 390:423 Here, we determined whether CXCR4 expression is affected by O-GlcNAcylation of NF-κB in lung metastasis of cervical cancer. 28681591 4 47 theme transferase 482:492 arg1 levels 444:449 elevated levels 435:449 elevated levels of O-linked-N-actylglucosamine transferase (OGT) and O-GlcNAcylation in cervical cancer cells 435:543 We found elevated levels of O-linked-N-actylglucosamine transferase (OGT) and O-GlcNAcylation in cervical cancer cells compared to those in non-malignant epithelial cells and detected increased expression of NF-κB p65 (p65) and CXCR4 in cervical cancer cells. 28681591 9 48 from mice 1400:1403 arg1 tissues 1387:1393 tissues 1387:1393 tissues from mice engrafted with shCTL cells 1387:1430 In addition, lung tissues from mice engrafted with shOGT cells exhibited lower p65 and CXCR4 immunoreactivity compared to tissues from mice engrafted with shCTL cells. 28681591 8 49 theme HeLa 1104:1107 arg1 cells 1109:1113 OGT-knockdown HeLa cells 1090:1113 OGT-knockdown HeLa cells (shOGT) 1090:1121 Lung tissues from mice engrafted with OGT-knockdown HeLa cells (shOGT) exhibited lower expression of Ki-67 and HPV E6 and E7 oncogenes compared to lung tissues from mice engrafted with control HeLa cells (shCTL). 28681591 8 49 theme HeLa 1104:1107 arg1 shOGT 1116:1120 shOGT 1116:1120 shOGT 1116:1120 Lung tissues from mice engrafted with OGT-knockdown HeLa cells (shOGT) exhibited lower expression of Ki-67 and HPV E6 and E7 oncogenes compared to lung tissues from mice engrafted with control HeLa cells (shCTL). 28681591 2 50 from expression 200:209 arg1 cells 221:225 cancer cells 214:225 cancer cells 214:225 NF-κB regulates CXCR4 expression in cancer cells, and O-GlcNAc modification of NF-κB promotes its transcriptional activity. 28681591 0 51 theme Cervical 53:60 arg1 Cells 69:73 Cervical Cancer Cells 53:73 Cervical Cancer Cells 53:73 O-GlcNAcylation of NF-κB Promotes Lung Metastasis of Cervical Cancer Cells via Upregulation of CXCR4 Expression. 28681591 5 52 theme p65 736:738 arg1 O-GlcNAcylation 717:731 the O-GlcNAcylation 713:731 the O-GlcNAcylation of p65 713:738 Knockdown of OGT inhibited the O-GlcNAcylation of p65 and decreased CXCR4 expression levels in HeLa cells. 28681591 8 53 theme Ki-67 1153:1157 arg1 E6 1167:1168 Ki-67 and HPV E6 and E7 oncogenes 1153:1185 E6 1167:1168 Lung tissues from mice engrafted with OGT-knockdown HeLa cells (shOGT) exhibited lower expression of Ki-67 and HPV E6 and E7 oncogenes compared to lung tissues from mice engrafted with control HeLa cells (shCTL). 28681591 3 54 from O-GlcNAcylation 362:376 arg1 metastasis 395:404 lung metastasis 390:404 lung metastasis of cervical cancer 390:423 Here, we determined whether CXCR4 expression is affected by O-GlcNAcylation of NF-κB in lung metastasis of cervical cancer. 28681591 9 55 theme shCTL 1420:1424 arg1 cells 1426:1430 shCTL cells 1420:1430 shCTL cells 1420:1430 In addition, lung tissues from mice engrafted with shOGT cells exhibited lower p65 and CXCR4 immunoreactivity compared to tissues from mice engrafted with shCTL cells. 28681591 1 56 theme C-X-C 113:117 arg1 receptor 129:136 C-X-C chemokine receptor 4 113:138 C-X-C chemokine receptor 4 (CXCR4) 113:146 C-X-C chemokine receptor 4 (CXCR4) stimulates cancer metastasis. 28681591 1 56 theme C-X-C 113:117 arg1 CXCR4 141:145 CXCR4 141:145 CXCR4 141:145 C-X-C chemokine receptor 4 (CXCR4) stimulates cancer metastasis. 28681591 4 57 from levels 444:449 arg1 cells 539:543 cervical cancer cells 523:543 cervical cancer cells 523:543 We found elevated levels of O-linked-N-actylglucosamine transferase (OGT) and O-GlcNAcylation in cervical cancer cells compared to those in non-malignant epithelial cells and detected increased expression of NF-κB p65 (p65) and CXCR4 in cervical cancer cells. 28681591 8 58 from mice 1217:1220 arg1 tissues 1204:1210 lung tissues 1199:1210 lung tissues from mice engrafted with control HeLa cells (shCTL) 1199:1262 Lung tissues from mice engrafted with OGT-knockdown HeLa cells (shOGT) exhibited lower expression of Ki-67 and HPV E6 and E7 oncogenes compared to lung tissues from mice engrafted with control HeLa cells (shCTL). 28681591 2 59 theme cancer 214:219 arg1 cells 221:225 cancer cells 214:225 cancer cells 214:225 NF-κB regulates CXCR4 expression in cancer cells, and O-GlcNAc modification of NF-κB promotes its transcriptional activity. 28681591 1 60 theme chemokine 119:127 arg1 receptor 129:136 C-X-C chemokine receptor 4 113:138 C-X-C chemokine receptor 4 (CXCR4) 113:146 C-X-C chemokine receptor 4 (CXCR4) stimulates cancer metastasis. 28681591 1 60 theme chemokine 119:127 arg1 CXCR4 141:145 CXCR4 141:145 CXCR4 141:145 C-X-C chemokine receptor 4 (CXCR4) stimulates cancer metastasis. 28681591 7 61 theme DON 957:959 arg1 treatment 962:970 6-Diazo-5-oxo-L-norleucine (DON) treatment 929:970 6-Diazo-5-oxo-L-norleucine (DON) treatment 929:970 Inhibition of O-GlcNAcylation by 6-Diazo-5-oxo-L-norleucine (DON) treatment decreased p65 activation, eventually inhibiting CXCR4 expression in HeLa cells. 28681591 8 62 theme HPV 1163:1165 arg1 E6 1167:1168 Ki-67 and HPV E6 and E7 oncogenes 1153:1185 E6 1167:1168 Lung tissues from mice engrafted with OGT-knockdown HeLa cells (shOGT) exhibited lower expression of Ki-67 and HPV E6 and E7 oncogenes compared to lung tissues from mice engrafted with control HeLa cells (shCTL). 28681591 7 63 theme p65 982:984 arg1 activation 986:995 p65 activation 982:995 p65 activation 982:995 Inhibition of O-GlcNAcylation by 6-Diazo-5-oxo-L-norleucine (DON) treatment decreased p65 activation, eventually inhibiting CXCR4 expression in HeLa cells. 28681591 2 64 theme NF-κB 257:261 arg1 modification 241:252 O-GlcNAc modification 232:252 O-GlcNAc modification of NF-κB 232:261 NF-κB regulates CXCR4 expression in cancer cells, and O-GlcNAc modification of NF-κB promotes its transcriptional activity. 28681591 7 65 theme CXCR4 1020:1024 arg1 expression 1026:1035 CXCR4 expression 1020:1035 CXCR4 expression in HeLa cells 1020:1049 Inhibition of O-GlcNAcylation by 6-Diazo-5-oxo-L-norleucine (DON) treatment decreased p65 activation, eventually inhibiting CXCR4 expression in HeLa cells. 28681591 4 66 theme NF-κB 634:638 arg1 p65 645:647 p65 645:647 p65 645:647 We found elevated levels of O-linked-N-actylglucosamine transferase (OGT) and O-GlcNAcylation in cervical cancer cells compared to those in non-malignant epithelial cells and detected increased expression of NF-κB p65 (p65) and CXCR4 in cervical cancer cells. 28681591 4 66 theme NF-κB 634:638 arg1 p65 640:642 NF-κB p65 634:642 NF-κB p65 (p65) 634:648 We found elevated levels of O-linked-N-actylglucosamine transferase (OGT) and O-GlcNAcylation in cervical cancer cells compared to those in non-malignant epithelial cells and detected increased expression of NF-κB p65 (p65) and CXCR4 in cervical cancer cells. 28681591 5 67 theme OGT 699:701 arg1 Knockdown 686:694 Knockdown 686:694 Knockdown of OGT 686:701 Knockdown of OGT inhibited the O-GlcNAcylation of p65 and decreased CXCR4 expression levels in HeLa cells. 28681591 2 68 theme CXCR4 194:198 arg1 expression 200:209 CXCR4 expression 194:209 CXCR4 expression in cancer cells 194:225 NF-κB regulates CXCR4 expression in cancer cells, and O-GlcNAc modification of NF-κB promotes its transcriptional activity. 28681591 7 69 theme HeLa 1040:1043 arg1 cells 1045:1049 HeLa cells 1040:1049 HeLa cells 1040:1049 Inhibition of O-GlcNAcylation by 6-Diazo-5-oxo-L-norleucine (DON) treatment decreased p65 activation, eventually inhibiting CXCR4 expression in HeLa cells. 28681591 10 70 theme cells 1535:1539 arg1 metastasis 1505:1514 lung metastasis 1500:1514 lung metastasis of cervical cancer cells 1500:1539 Taken together, our data suggest that p65 O-GlcNAcylation promotes lung metastasis of cervical cancer cells by activating CXCR4 expression. 28681591 7 71 theme 6-Diazo-5-oxo-L-norleucine 929:954 arg1 treatment 962:970 6-Diazo-5-oxo-L-norleucine (DON) treatment 929:970 6-Diazo-5-oxo-L-norleucine (DON) treatment 929:970 Inhibition of O-GlcNAcylation by 6-Diazo-5-oxo-L-norleucine (DON) treatment decreased p65 activation, eventually inhibiting CXCR4 expression in HeLa cells. 28681591 8 72 theme control 1237:1243 arg1 shCTL 1257:1261 shCTL 1257:1261 shCTL 1257:1261 Lung tissues from mice engrafted with OGT-knockdown HeLa cells (shOGT) exhibited lower expression of Ki-67 and HPV E6 and E7 oncogenes compared to lung tissues from mice engrafted with control HeLa cells (shCTL). 28681591 8 72 theme control 1237:1243 arg1 cells 1250:1254 control HeLa cells 1237:1254 control HeLa cells (shCTL) 1237:1262 Lung tissues from mice engrafted with OGT-knockdown HeLa cells (shOGT) exhibited lower expression of Ki-67 and HPV E6 and E7 oncogenes compared to lung tissues from mice engrafted with control HeLa cells (shCTL). 28681591 3 73 theme CXCR4 330:334 arg1 expression 336:345 CXCR4 expression 330:345 CXCR4 expression 330:345 Here, we determined whether CXCR4 expression is affected by O-GlcNAcylation of NF-κB in lung metastasis of cervical cancer. 28681591 5 74 from levels 771:776 arg1 cells 786:790 HeLa cells 781:790 HeLa cells 781:790 Knockdown of OGT inhibited the O-GlcNAcylation of p65 and decreased CXCR4 expression levels in HeLa cells. 28681591 9 75 from mice 1296:1299 arg1 tissues 1283:1289 lung tissues 1278:1289 lung tissues from mice engrafted with shOGT cells 1278:1326 In addition, lung tissues from mice engrafted with shOGT cells exhibited lower p65 and CXCR4 immunoreactivity compared to tissues from mice engrafted with shCTL cells. 28681591 2 76 mod modification 241:252 arg3 O-GlcNAc 232:239 O-GlcNAc modification 232:252 O-GlcNAc modification of NF-κB 232:261 NF-κB regulates CXCR4 expression in cancer cells, and O-GlcNAc modification of NF-κB promotes its transcriptional activity. 28681591 2 76 mod modification 241:252 arg1 NF-κB 257:261 NF-κB 257:261 NF-κB 257:261 NF-κB regulates CXCR4 expression in cancer cells, and O-GlcNAc modification of NF-κB promotes its transcriptional activity. 28681591 6 77 theme CXCR4 871:875 arg1 levels 888:893 CXCR4 expression levels 871:893 CXCR4 expression levels 871:893 Thiamet G treatment increased O-GlcNAcylated p65, which subsequently enhanced CXCR4 expression levels. 28681591 10 78 theme CXCR4 1555:1559 arg1 expression 1561:1570 CXCR4 expression 1555:1570 CXCR4 expression 1555:1570 Taken together, our data suggest that p65 O-GlcNAcylation promotes lung metastasis of cervical cancer cells by activating CXCR4 expression. 28681591 0 79 theme Cancer 62:67 arg1 Cells 69:73 Cervical Cancer Cells 53:73 Cervical Cancer Cells 53:73 O-GlcNAcylation of NF-κB Promotes Lung Metastasis of Cervical Cancer Cells via Upregulation of CXCR4 Expression. 28681591 2 80 theme O-GlcNAc 232:239 arg1 modification 241:252 O-GlcNAc modification 232:252 O-GlcNAc modification of NF-κB 232:261 NF-κB regulates CXCR4 expression in cancer cells, and O-GlcNAc modification of NF-κB promotes its transcriptional activity. 28681591 9 81 theme lower 1338:1342 arg1 immunoreactivity 1358:1373 lower p65 and CXCR4 immunoreactivity 1338:1373 lower p65 and CXCR4 immunoreactivity 1338:1373 In addition, lung tissues from mice engrafted with shOGT cells exhibited lower p65 and CXCR4 immunoreactivity compared to tissues from mice engrafted with shCTL cells. 28681591 7 82 theme O-GlcNAcylation 910:924 arg1 Inhibition 896:905 Inhibition 896:905 Inhibition of O-GlcNAcylation by 6-Diazo-5-oxo-L-norleucine (DON) treatment 896:970 Inhibition of O-GlcNAcylation by 6-Diazo-5-oxo-L-norleucine (DON) treatment decreased p65 activation, eventually inhibiting CXCR4 expression in HeLa cells. 28681591 4 83 theme p65 640:642 arg1 expression 620:629 increased expression 610:629 increased expression of NF-κB p65 (p65) and CXCR4 610:658 We found elevated levels of O-linked-N-actylglucosamine transferase (OGT) and O-GlcNAcylation in cervical cancer cells compared to those in non-malignant epithelial cells and detected increased expression of NF-κB p65 (p65) and CXCR4 in cervical cancer cells. 28246173 2 0 theme central 364:370 arg1 system 380:385 the central nervous system 360:385 the central nervous system 360:385 We selectively targeted the O-GlcNAcase (Oga) gene in the mouse brain to define the role of O-GlcNAc cycling in the central nervous system. 28246173 4 1 theme brain 626:630 arg1 differentiation 632:646 delayed brain differentiation 618:646 delayed brain differentiation 618:646 Anatomical defects in the Oga knockout included delayed brain differentiation and neurogenesis as well as abnormal proliferation accompanying a developmental delay. 28246173 6 2 theme pronounced 895:904 arg1 changes 906:912 pronounced changes 895:912 pronounced changes in expression of pluripotency markers, including Sox2, Nanog, and Otx2 895:983 In Oga KO mouse ES cells, we observed pronounced changes in expression of pluripotency markers, including Sox2, Nanog, and Otx2. 28246173 2 3 from role 332:335 arg1 system 380:385 the central nervous system 360:385 the central nervous system 360:385 We selectively targeted the O-GlcNAcase (Oga) gene in the mouse brain to define the role of O-GlcNAc cycling in the central nervous system. 28246173 4 4 theme delayed 618:624 arg1 differentiation 632:646 delayed brain differentiation 618:646 delayed brain differentiation 618:646 Anatomical defects in the Oga knockout included delayed brain differentiation and neurogenesis as well as abnormal proliferation accompanying a developmental delay. 28246173 6 5 theme ES 873:874 arg1 cells 876:880 Oga KO mouse ES cells 860:880 Oga KO mouse ES cells 860:880 In Oga KO mouse ES cells, we observed pronounced changes in expression of pluripotency markers, including Sox2, Nanog, and Otx2. 28246173 1 6 from brain 176:180 arg1 abundant 160:167 abundant 160:167 abundant 160:167 Nutrient-driven O-GlcNAcylation is strikingly abundant in the brain and has been linked to development and neurodegenerative disease. 28246173 5 7 theme differentiating 819:833 arg1 cells 850:854 differentiating embryonic stem cells 819:854 differentiating embryonic stem cells 819:854 The molecular basis for these defects included transcriptional changes accompanying differentiating embryonic stem cells. 28246173 4 8 dep included 609:616 arg1 accompanying 699:710 accompanying 699:710 included delayed brain differentiation and neurogenesis as well as abnormal proliferation accompanying a developmental delay 609:732 Anatomical defects in the Oga knockout included delayed brain differentiation and neurogenesis as well as abnormal proliferation accompanying a developmental delay. 28246173 0 9 link O-linked 16:23 arg1 N-acetylglucosamine 25:43 O-linked N-acetylglucosamine 16:43 Nutrient-driven O-linked N-acetylglucosamine (O-GlcNAc) cycling 0:62 Nutrient-driven O-linked N-acetylglucosamine (O-GlcNAc) cycling impacts neurodevelopmental timing and metabolism. 28246173 0 9 link O-linked 16:23 arg1 O-GlcNAc 46:53 O-GlcNAc 46:53 O-GlcNAc 46:53 Nutrient-driven O-linked N-acetylglucosamine (O-GlcNAc) cycling impacts neurodevelopmental timing and metabolism. 28246173 2 10 theme mouse 306:310 arg1 brain 312:316 the mouse brain 302:316 the mouse brain 302:316 We selectively targeted the O-GlcNAcase (Oga) gene in the mouse brain to define the role of O-GlcNAc cycling in the central nervous system. 28246173 5 11 theme embryonic 835:843 arg1 cells 850:854 differentiating embryonic stem cells 819:854 differentiating embryonic stem cells 819:854 The molecular basis for these defects included transcriptional changes accompanying differentiating embryonic stem cells. 28246173 6 12 from changes 906:912 arg1 expression 917:926 expression 917:926 expression of pluripotency markers, including Sox2, Nanog, and Otx2 917:983 In Oga KO mouse ES cells, we observed pronounced changes in expression of pluripotency markers, including Sox2, Nanog, and Otx2. 28246173 4 13 theme abnormal 676:683 arg1 proliferation 685:697 abnormal proliferation 676:697 abnormal proliferation 676:697 Anatomical defects in the Oga knockout included delayed brain differentiation and neurogenesis as well as abnormal proliferation accompanying a developmental delay. 28246173 5 14 theme stem 845:848 arg1 cells 850:854 differentiating embryonic stem cells 819:854 differentiating embryonic stem cells 819:854 The molecular basis for these defects included transcriptional changes accompanying differentiating embryonic stem cells. 28246173 3 15 theme pleiotropic 470:480 arg1 obesity 516:522 early-onset obesity 504:522 early-onset obesity 504:522 Brain knockout animals exhibited dramatically increased brain O-GlcNAc levels and pleiotropic phenotypes, including early-onset obesity, growth defects, and metabolic dysregulation. 28246173 3 15 theme pleiotropic 470:480 arg1 defects 532:538 growth defects 525:538 growth defects 525:538 Brain knockout animals exhibited dramatically increased brain O-GlcNAc levels and pleiotropic phenotypes, including early-onset obesity, growth defects, and metabolic dysregulation. 28246173 3 15 theme pleiotropic 470:480 arg1 phenotypes 482:491 pleiotropic phenotypes 470:491 pleiotropic phenotypes 470:491 Brain knockout animals exhibited dramatically increased brain O-GlcNAc levels and pleiotropic phenotypes, including early-onset obesity, growth defects, and metabolic dysregulation. 28246173 3 15 theme pleiotropic 470:480 arg1 dysregulation 555:567 metabolic dysregulation 545:567 metabolic dysregulation 545:567 Brain knockout animals exhibited dramatically increased brain O-GlcNAc levels and pleiotropic phenotypes, including early-onset obesity, growth defects, and metabolic dysregulation. 28246173 0 16 theme O-linked 16:23 arg1 N-acetylglucosamine 25:43 O-linked N-acetylglucosamine 16:43 Nutrient-driven O-linked N-acetylglucosamine (O-GlcNAc) cycling 0:62 Nutrient-driven O-linked N-acetylglucosamine (O-GlcNAc) cycling impacts neurodevelopmental timing and metabolism. 28246173 0 16 theme O-linked 16:23 arg1 O-GlcNAc 46:53 O-GlcNAc 46:53 O-GlcNAc 46:53 Nutrient-driven O-linked N-acetylglucosamine (O-GlcNAc) cycling impacts neurodevelopmental timing and metabolism. 28246173 4 17 theme developmental 714:726 arg1 delay 728:732 a developmental delay 712:732 a developmental delay 712:732 Anatomical defects in the Oga knockout included delayed brain differentiation and neurogenesis as well as abnormal proliferation accompanying a developmental delay. 28246173 3 18 theme O-GlcNAc 450:457 arg1 obesity 516:522 early-onset obesity 504:522 early-onset obesity 504:522 Brain knockout animals exhibited dramatically increased brain O-GlcNAc levels and pleiotropic phenotypes, including early-onset obesity, growth defects, and metabolic dysregulation. 28246173 3 18 theme O-GlcNAc 450:457 arg1 defects 532:538 growth defects 525:538 growth defects 525:538 Brain knockout animals exhibited dramatically increased brain O-GlcNAc levels and pleiotropic phenotypes, including early-onset obesity, growth defects, and metabolic dysregulation. 28246173 3 18 theme O-GlcNAc 450:457 arg1 levels 459:464 dramatically increased brain O-GlcNAc levels 421:464 dramatically increased brain O-GlcNAc levels 421:464 Brain knockout animals exhibited dramatically increased brain O-GlcNAc levels and pleiotropic phenotypes, including early-onset obesity, growth defects, and metabolic dysregulation. 28246173 3 18 theme O-GlcNAc 450:457 arg1 dysregulation 555:567 metabolic dysregulation 545:567 metabolic dysregulation 545:567 Brain knockout animals exhibited dramatically increased brain O-GlcNAc levels and pleiotropic phenotypes, including early-onset obesity, growth defects, and metabolic dysregulation. 28246173 0 19 theme Nutrient-driven 0:14 arg1 cycling 56:62 Nutrient-driven O-linked N-acetylglucosamine (O-GlcNAc) cycling 0:62 Nutrient-driven O-linked N-acetylglucosamine (O-GlcNAc) cycling 0:62 Nutrient-driven O-linked N-acetylglucosamine (O-GlcNAc) cycling impacts neurodevelopmental timing and metabolism. 28246173 6 20 theme mouse 867:871 arg1 cells 876:880 Oga KO mouse ES cells 860:880 Oga KO mouse ES cells 860:880 In Oga KO mouse ES cells, we observed pronounced changes in expression of pluripotency markers, including Sox2, Nanog, and Otx2. 28246173 1 21 theme Nutrient-driven 114:128 arg1 O-GlcNAcylation 130:144 Nutrient-driven O-GlcNAcylation 114:144 Nutrient-driven O-GlcNAcylation 114:144 Nutrient-driven O-GlcNAcylation is strikingly abundant in the brain and has been linked to development and neurodegenerative disease. 28246173 7 22 from role 1076:1079 arg1 plasticity 1131:1140 developmental plasticity 1117:1140 developmental plasticity 1117:1140 These findings link the O-GlcNAc modification to mammalian neurogenesis and highlight the role of this nutrient-sensing pathway in developmental plasticity and metabolic homeostasis. 28246173 7 22 from role 1076:1079 arg1 homeostasis 1156:1166 metabolic homeostasis 1146:1166 metabolic homeostasis 1146:1166 These findings link the O-GlcNAc modification to mammalian neurogenesis and highlight the role of this nutrient-sensing pathway in developmental plasticity and metabolic homeostasis. 28246173 7 23 attach link 1001:1004 arg2 findings 992:999 These findings 986:999 These findings 986:999 These findings link the O-GlcNAc modification to mammalian neurogenesis and highlight the role of this nutrient-sensing pathway in developmental plasticity and metabolic homeostasis. 28246173 7 23 attach link 1001:1004 arg1 neurogenesis 1045:1056 mammalian neurogenesis 1035:1056 mammalian neurogenesis 1035:1056 These findings link the O-GlcNAc modification to mammalian neurogenesis and highlight the role of this nutrient-sensing pathway in developmental plasticity and metabolic homeostasis. 28246173 1 24 from abundant 160:167 arg1 brain 176:180 the brain 172:180 the brain 172:180 Nutrient-driven O-GlcNAcylation is strikingly abundant in the brain and has been linked to development and neurodegenerative disease. 28246173 7 25 theme mammalian 1035:1043 arg1 neurogenesis 1045:1056 mammalian neurogenesis 1035:1056 mammalian neurogenesis 1035:1056 These findings link the O-GlcNAc modification to mammalian neurogenesis and highlight the role of this nutrient-sensing pathway in developmental plasticity and metabolic homeostasis. 28246173 1 26 theme neurodegenerative 221:237 arg1 disease 239:245 neurodegenerative disease 221:245 neurodegenerative disease 221:245 Nutrient-driven O-GlcNAcylation is strikingly abundant in the brain and has been linked to development and neurodegenerative disease. 28246173 0 27 theme N-acetylglucosamine 25:43 arg1 cycling 56:62 Nutrient-driven O-linked N-acetylglucosamine (O-GlcNAc) cycling 0:62 Nutrient-driven O-linked N-acetylglucosamine (O-GlcNAc) cycling 0:62 Nutrient-driven O-linked N-acetylglucosamine (O-GlcNAc) cycling impacts neurodevelopmental timing and metabolism. 28246173 7 28 theme metabolic 1146:1154 arg1 homeostasis 1156:1166 metabolic homeostasis 1146:1166 metabolic homeostasis 1146:1166 These findings link the O-GlcNAc modification to mammalian neurogenesis and highlight the role of this nutrient-sensing pathway in developmental plasticity and metabolic homeostasis. 28246173 2 29 from gene 294:297 arg1 brain 312:316 the mouse brain 302:316 the mouse brain 302:316 We selectively targeted the O-GlcNAcase (Oga) gene in the mouse brain to define the role of O-GlcNAc cycling in the central nervous system. 28246173 3 30 theme early-onset 504:514 arg1 obesity 516:522 early-onset obesity 504:522 early-onset obesity 504:522 Brain knockout animals exhibited dramatically increased brain O-GlcNAc levels and pleiotropic phenotypes, including early-onset obesity, growth defects, and metabolic dysregulation. 28246173 3 31 theme increased 434:442 arg1 obesity 516:522 early-onset obesity 504:522 early-onset obesity 504:522 Brain knockout animals exhibited dramatically increased brain O-GlcNAc levels and pleiotropic phenotypes, including early-onset obesity, growth defects, and metabolic dysregulation. 28246173 3 31 theme increased 434:442 arg1 defects 532:538 growth defects 525:538 growth defects 525:538 Brain knockout animals exhibited dramatically increased brain O-GlcNAc levels and pleiotropic phenotypes, including early-onset obesity, growth defects, and metabolic dysregulation. 28246173 3 31 theme increased 434:442 arg1 levels 459:464 dramatically increased brain O-GlcNAc levels 421:464 dramatically increased brain O-GlcNAc levels 421:464 Brain knockout animals exhibited dramatically increased brain O-GlcNAc levels and pleiotropic phenotypes, including early-onset obesity, growth defects, and metabolic dysregulation. 28246173 3 31 theme increased 434:442 arg1 dysregulation 555:567 metabolic dysregulation 545:567 metabolic dysregulation 545:567 Brain knockout animals exhibited dramatically increased brain O-GlcNAc levels and pleiotropic phenotypes, including early-onset obesity, growth defects, and metabolic dysregulation. 28246173 4 32 theme knockout 600:607 arg1 Oga 596:598 the Oga knockout 592:607 the Oga knockout 592:607 Anatomical defects in the Oga knockout included delayed brain differentiation and neurogenesis as well as abnormal proliferation accompanying a developmental delay. 28246173 5 33 theme transcriptional 782:796 arg1 changes 798:804 transcriptional changes 782:804 transcriptional changes accompanying differentiating embryonic stem cells 782:854 The molecular basis for these defects included transcriptional changes accompanying differentiating embryonic stem cells. 28246173 1 34 attach linked 195:200 arg1 development 205:215 development 205:215 development 205:215 Nutrient-driven O-GlcNAcylation is strikingly abundant in the brain and has been linked to development and neurodegenerative disease. 28246173 1 34 attach linked 195:200 arg1 disease 239:245 neurodegenerative disease 221:245 neurodegenerative disease 221:245 Nutrient-driven O-GlcNAcylation is strikingly abundant in the brain and has been linked to development and neurodegenerative disease. 28246173 1 34 attach linked 195:200 arg2 O-GlcNAcylation 130:144 Nutrient-driven O-GlcNAcylation 114:144 Nutrient-driven O-GlcNAcylation 114:144 Nutrient-driven O-GlcNAcylation is strikingly abundant in the brain and has been linked to development and neurodegenerative disease. 28246173 2 35 theme O-GlcNAcase 276:286 arg1 gene 294:297 the O-GlcNAcase (Oga) gene 272:297 the O-GlcNAcase (Oga) gene in the mouse brain 272:316 We selectively targeted the O-GlcNAcase (Oga) gene in the mouse brain to define the role of O-GlcNAc cycling in the central nervous system. 28246173 3 36 theme brain 444:448 arg1 obesity 516:522 early-onset obesity 504:522 early-onset obesity 504:522 Brain knockout animals exhibited dramatically increased brain O-GlcNAc levels and pleiotropic phenotypes, including early-onset obesity, growth defects, and metabolic dysregulation. 28246173 3 36 theme brain 444:448 arg1 defects 532:538 growth defects 525:538 growth defects 525:538 Brain knockout animals exhibited dramatically increased brain O-GlcNAc levels and pleiotropic phenotypes, including early-onset obesity, growth defects, and metabolic dysregulation. 28246173 3 36 theme brain 444:448 arg1 levels 459:464 dramatically increased brain O-GlcNAc levels 421:464 dramatically increased brain O-GlcNAc levels 421:464 Brain knockout animals exhibited dramatically increased brain O-GlcNAc levels and pleiotropic phenotypes, including early-onset obesity, growth defects, and metabolic dysregulation. 28246173 3 36 theme brain 444:448 arg1 dysregulation 555:567 metabolic dysregulation 545:567 metabolic dysregulation 545:567 Brain knockout animals exhibited dramatically increased brain O-GlcNAc levels and pleiotropic phenotypes, including early-onset obesity, growth defects, and metabolic dysregulation. 28246173 4 37 theme Anatomical 570:579 arg1 defects 581:587 Anatomical defects 570:587 Anatomical defects in the Oga knockout 570:607 Anatomical defects in the Oga knockout included delayed brain differentiation and neurogenesis as well as abnormal proliferation accompanying a developmental delay. 28246173 4 38 from defects 581:587 arg1 Oga 596:598 the Oga knockout 592:607 the Oga knockout 592:607 Anatomical defects in the Oga knockout included delayed brain differentiation and neurogenesis as well as abnormal proliferation accompanying a developmental delay. 28246173 6 39 theme markers 944:950 arg1 expression 917:926 expression 917:926 expression of pluripotency markers, including Sox2, Nanog, and Otx2 917:983 In Oga KO mouse ES cells, we observed pronounced changes in expression of pluripotency markers, including Sox2, Nanog, and Otx2. 28246173 6 40 theme Oga 860:862 arg1 cells 876:880 Oga KO mouse ES cells 860:880 Oga KO mouse ES cells 860:880 In Oga KO mouse ES cells, we observed pronounced changes in expression of pluripotency markers, including Sox2, Nanog, and Otx2. 28246173 5 41 theme molecular 739:747 arg1 basis 749:753 The molecular basis 735:753 The molecular basis for these defects 735:771 The molecular basis for these defects included transcriptional changes accompanying differentiating embryonic stem cells. 28246173 6 42 theme pluripotency 931:942 arg1 Nanog 969:973 Nanog 969:973 Nanog 969:973 In Oga KO mouse ES cells, we observed pronounced changes in expression of pluripotency markers, including Sox2, Nanog, and Otx2. 28246173 6 42 theme pluripotency 931:942 arg1 markers 944:950 pluripotency markers 931:950 pluripotency markers 931:950 In Oga KO mouse ES cells, we observed pronounced changes in expression of pluripotency markers, including Sox2, Nanog, and Otx2. 28246173 6 42 theme pluripotency 931:942 arg1 Sox2 963:966 Sox2 963:966 Sox2 963:966 In Oga KO mouse ES cells, we observed pronounced changes in expression of pluripotency markers, including Sox2, Nanog, and Otx2. 28246173 6 42 theme pluripotency 931:942 arg1 Otx2 980:983 Otx2 980:983 Otx2 980:983 In Oga KO mouse ES cells, we observed pronounced changes in expression of pluripotency markers, including Sox2, Nanog, and Otx2. 28246173 7 43 theme pathway 1106:1112 arg1 role 1076:1079 the role 1072:1079 the role of this nutrient-sensing pathway in developmental plasticity and metabolic homeostasis 1072:1166 These findings link the O-GlcNAc modification to mammalian neurogenesis and highlight the role of this nutrient-sensing pathway in developmental plasticity and metabolic homeostasis. 28246173 3 44 theme growth 525:530 arg1 defects 532:538 growth defects 525:538 growth defects 525:538 Brain knockout animals exhibited dramatically increased brain O-GlcNAc levels and pleiotropic phenotypes, including early-onset obesity, growth defects, and metabolic dysregulation. 28246173 2 45 theme cycling 349:355 arg1 role 332:335 the role 328:335 the role of O-GlcNAc cycling in the central nervous system 328:385 We selectively targeted the O-GlcNAcase (Oga) gene in the mouse brain to define the role of O-GlcNAc cycling in the central nervous system. 28246173 6 46 theme KO 864:865 arg1 cells 876:880 Oga KO mouse ES cells 860:880 Oga KO mouse ES cells 860:880 In Oga KO mouse ES cells, we observed pronounced changes in expression of pluripotency markers, including Sox2, Nanog, and Otx2. 28246173 2 47 theme O-GlcNAc 340:347 arg1 cycling 349:355 O-GlcNAc cycling 340:355 O-GlcNAc cycling 340:355 We selectively targeted the O-GlcNAcase (Oga) gene in the mouse brain to define the role of O-GlcNAc cycling in the central nervous system. 28246173 7 48 theme developmental 1117:1129 arg1 plasticity 1131:1140 developmental plasticity 1117:1140 developmental plasticity 1117:1140 These findings link the O-GlcNAc modification to mammalian neurogenesis and highlight the role of this nutrient-sensing pathway in developmental plasticity and metabolic homeostasis. 28246173 7 49 theme nutrient-sensing 1089:1104 arg1 pathway 1106:1112 this nutrient-sensing pathway 1084:1112 this nutrient-sensing pathway 1084:1112 These findings link the O-GlcNAc modification to mammalian neurogenesis and highlight the role of this nutrient-sensing pathway in developmental plasticity and metabolic homeostasis. 28246173 7 50 theme O-GlcNAc 1010:1017 arg1 modification 1019:1030 the O-GlcNAc modification 1006:1030 the O-GlcNAc modification 1006:1030 These findings link the O-GlcNAc modification to mammalian neurogenesis and highlight the role of this nutrient-sensing pathway in developmental plasticity and metabolic homeostasis. 28246173 2 51 theme Oga 289:291 arg1 gene 294:297 the O-GlcNAcase (Oga) gene 272:297 the O-GlcNAcase (Oga) gene in the mouse brain 272:316 We selectively targeted the O-GlcNAcase (Oga) gene in the mouse brain to define the role of O-GlcNAc cycling in the central nervous system. 28246173 3 52 theme metabolic 545:553 arg1 dysregulation 555:567 metabolic dysregulation 545:567 metabolic dysregulation 545:567 Brain knockout animals exhibited dramatically increased brain O-GlcNAc levels and pleiotropic phenotypes, including early-onset obesity, growth defects, and metabolic dysregulation. 28246173 3 53 theme knockout 394:401 arg1 animals 403:409 Brain knockout animals 388:409 Brain knockout animals 388:409 Brain knockout animals exhibited dramatically increased brain O-GlcNAc levels and pleiotropic phenotypes, including early-onset obesity, growth defects, and metabolic dysregulation. 28246173 0 54 theme neurodevelopmental 72:89 arg1 timing 91:96 neurodevelopmental timing 72:96 neurodevelopmental timing 72:96 Nutrient-driven O-linked N-acetylglucosamine (O-GlcNAc) cycling impacts neurodevelopmental timing and metabolism. 28246173 3 55 theme Brain 388:392 arg1 animals 403:409 Brain knockout animals 388:409 Brain knockout animals 388:409 Brain knockout animals exhibited dramatically increased brain O-GlcNAc levels and pleiotropic phenotypes, including early-onset obesity, growth defects, and metabolic dysregulation. 28246173 2 56 theme nervous 372:378 arg1 system 380:385 the central nervous system 360:385 the central nervous system 360:385 We selectively targeted the O-GlcNAcase (Oga) gene in the mouse brain to define the role of O-GlcNAc cycling in the central nervous system. 27965094 8 0 theme isoforms 967:974 arg1 knockdown 945:953 knockdown 945:953 knockdown of T1 or T4 isoforms 945:974 While knockdown of T1 or T4 isoforms did not change the expression of osteopontin (OPN), COLLI, receptor activator for nuclear factor-κB ligand (RANKL) and transforming growth factor-β (TGF-β). 27965094 6 1 theme ppGalNAc-T1decreased 767:786 arg1 levels 793:798 ppGalNAc-T1decreased mRNA levels 767:798 ppGalNAc-T1decreased mRNA levels of osteocalcin (OC), osteoprotegerin (OPG) 767:841 Knockdown of ppGalNAc-T1decreased mRNA levels of osteocalcin (OC), osteoprotegerin (OPG). 27965094 7 2 theme receptor 923:930 arg1 levels 891:896 mRNA levels 886:896 mRNA levels of OC, OPG and vitamin D receptor (VDR) 886:936 Knockdown ofppGalNAc-T4 isoform decreased mRNA levels of OC, OPG and vitamin D receptor (VDR). 27965094 5 3 theme protein 711:717 arg1 levels 719:724 mRNA and protein levels 702:724 mRNA and protein levels of bone sialoprotein (BSP) 702:751 Knockdown of ppGalNAc-T1 or -T4 decreased mRNA and protein levels of bone sialoprotein (BSP). 27965094 10 4 theme isoformsplay 1391:1402 arg1 roles 1374:1378 distinct roles 1365:1378 distinct roles ppGalNAc-T isoformsplay in regulating osteogenesis in vitro 1365:1438 We also found that ppGalNAc-T1 and -T4 affected the expression of different osteogenic factors, suggesting distinct roles ppGalNAc-T isoformsplay in regulating osteogenesis in vitro. 27965094 1 5 dep family 113:118 arg1 N-Acetylgalactosaminlytransfersases 147:181 N-Acetylgalactosaminlytransfersases 147:181 The family of UDP-GalNAc polypeptide: N-Acetylgalactosaminlytransfersases (ppGalNAcTs) 109:194 The family of UDP-GalNAc polypeptide: N-Acetylgalactosaminlytransfersases (ppGalNAcTs) catalyzes the initial step of O-linked protein glycosylation. 27965094 1 5 dep family 113:118 arg1 ppGalNAcTs 184:193 ppGalNAcTs 184:193 ppGalNAcTs 184:193 The family of UDP-GalNAc polypeptide: N-Acetylgalactosaminlytransfersases (ppGalNAcTs) catalyzes the initial step of O-linked protein glycosylation. 27965094 3 6 theme ppGalNAc-T 393:402 arg1 isoforms 404:411 ppGalNAc-T isoforms 393:411 ppGalNAc-T isoforms 393:411 Herein, we examined the effects of ppGalNAc-T isoforms on osteogenesis of MC3T3-E1 pre-osteoblasts. 27965094 10 7 theme distinct 1365:1372 arg1 roles 1374:1378 distinct roles 1365:1378 distinct roles ppGalNAc-T isoformsplay in regulating osteogenesis in vitro 1365:1438 We also found that ppGalNAc-T1 and -T4 affected the expression of different osteogenic factors, suggesting distinct roles ppGalNAc-T isoformsplay in regulating osteogenesis in vitro. 27965094 7 8 theme vitamin 913:919 arg1 VDR 933:935 VDR 933:935 VDR 933:935 Knockdown ofppGalNAc-T4 isoform decreased mRNA levels of OC, OPG and vitamin D receptor (VDR). 27965094 7 8 theme vitamin 913:919 arg1 receptor 923:930 vitamin D receptor 913:930 vitamin D receptor (VDR) 913:936 Knockdown ofppGalNAc-T4 isoform decreased mRNA levels of OC, OPG and vitamin D receptor (VDR). 27965094 3 9 theme isoforms 404:411 arg1 effects 382:388 the effects 378:388 the effects of ppGalNAc-T isoforms on osteogenesis of MC3T3-E1 pre-osteoblasts 378:455 Herein, we examined the effects of ppGalNAc-T isoforms on osteogenesis of MC3T3-E1 pre-osteoblasts. 27965094 2 10 theme important 326:334 arg1 role 336:339 an important role 323:339 an important role 323:339 Mucin-type O-glycoproteins are abundant in the bone and may play an important role in osteogenesis. 27965094 4 11 theme bone 639:642 arg1 mineralization 644:657 bone mineralization 639:657 bone mineralization 639:657 We found that ppGalNAc-T1 and -T4 isoforms were highly expressed during osteogenesis of MC3T3-E1 and their knockdown by short hairpin RNA (shRNA) decreased osteoblast formation and bone mineralization. 27965094 5 12 theme ppGalNAc-T1 673:683 arg1 Knockdown 660:668 Knockdown 660:668 Knockdown of ppGalNAc-T1 or -T4 660:690 Knockdown of ppGalNAc-T1 or -T4 decreased mRNA and protein levels of bone sialoprotein (BSP). 27965094 7 13 theme OC 901:902 arg1 levels 891:896 mRNA levels 886:896 mRNA levels of OC, OPG and vitamin D receptor (VDR) 886:936 Knockdown ofppGalNAc-T4 isoform decreased mRNA levels of OC, OPG and vitamin D receptor (VDR). 27965094 1 14 theme initial 210:216 arg1 step 218:221 the initial step 206:221 the initial step of O-linked protein glycosylation 206:255 The family of UDP-GalNAc polypeptide: N-Acetylgalactosaminlytransfersases (ppGalNAcTs) catalyzes the initial step of O-linked protein glycosylation. 27965094 4 15 theme MC3T3-E1 546:553 arg1 osteogenesis 530:541 osteogenesis 530:541 osteogenesis of MC3T3-E1 530:553 We found that ppGalNAc-T1 and -T4 isoforms were highly expressed during osteogenesis of MC3T3-E1 and their knockdown by short hairpin RNA (shRNA) decreased osteoblast formation and bone mineralization. 27965094 1 16 link O-linked 226:233 arg1 glycosylation 243:255 O-linked protein glycosylation 226:255 O-linked protein glycosylation 226:255 The family of UDP-GalNAc polypeptide: N-Acetylgalactosaminlytransfersases (ppGalNAcTs) catalyzes the initial step of O-linked protein glycosylation. 27965094 8 17 theme osteopontin 1009:1019 arg1 expression 995:1004 the expression 991:1004 the expression of osteopontin (OPN), COLLI, receptor activator for nuclear factor-κB ligand (RANKL) and transforming growth factor-β (TGF-β) 991:1130 While knockdown of T1 or T4 isoforms did not change the expression of osteopontin (OPN), COLLI, receptor activator for nuclear factor-κB ligand (RANKL) and transforming growth factor-β (TGF-β). 27965094 0 18 theme Isoform-specific 0:15 arg1 regulation 17:26 Isoform-specific regulation 0:26 Isoform-specific regulation of osteogenic factors by polypeptide N-Acetylgalactosaminyltransferases 1 and 4. 0:107 Isoform-specific regulation of osteogenic factors by polypeptide N-Acetylgalactosaminyltransferases 1 and 4. 27965094 10 19 theme osteogenic 1334:1343 arg1 factors 1345:1351 different osteogenic factors 1324:1351 different osteogenic factors 1324:1351 We also found that ppGalNAc-T1 and -T4 affected the expression of different osteogenic factors, suggesting distinct roles ppGalNAc-T isoformsplay in regulating osteogenesis in vitro. 27965094 8 20 theme nuclear 1058:1064 arg1 RANKL 1084:1088 RANKL 1084:1088 RANKL 1084:1088 While knockdown of T1 or T4 isoforms did not change the expression of osteopontin (OPN), COLLI, receptor activator for nuclear factor-κB ligand (RANKL) and transforming growth factor-β (TGF-β). 27965094 8 20 theme nuclear 1058:1064 arg1 ligand 1076:1081 nuclear factor-κB ligand 1058:1081 nuclear factor-κB ligand (RANKL) 1058:1089 While knockdown of T1 or T4 isoforms did not change the expression of osteopontin (OPN), COLLI, receptor activator for nuclear factor-κB ligand (RANKL) and transforming growth factor-β (TGF-β). 27965094 10 21 theme osteogenesis 1418:1429 arg1 in vitro 1431:1438 osteogenesis in vitro 1418:1438 osteogenesis in vitro 1418:1438 We also found that ppGalNAc-T1 and -T4 affected the expression of different osteogenic factors, suggesting distinct roles ppGalNAc-T isoformsplay in regulating osteogenesis in vitro. 27965094 2 22 from abundant 289:296 arg1 bone 305:308 the bone 301:308 the bone 301:308 Mucin-type O-glycoproteins are abundant in the bone and may play an important role in osteogenesis. 27965094 3 23 theme MC3T3-E1 432:439 arg1 pre-osteoblasts 441:455 MC3T3-E1 pre-osteoblasts 432:455 MC3T3-E1 pre-osteoblasts 432:455 Herein, we examined the effects of ppGalNAc-T isoforms on osteogenesis of MC3T3-E1 pre-osteoblasts. 27965094 7 24 theme Knockdown 844:852 arg1 isoform 868:874 Knockdown ofppGalNAc-T4 isoform 844:874 Knockdown ofppGalNAc-T4 isoform 844:874 Knockdown ofppGalNAc-T4 isoform decreased mRNA levels of OC, OPG and vitamin D receptor (VDR). 27965094 5 25 theme mRNA 702:705 arg1 levels 719:724 mRNA and protein levels 702:724 mRNA and protein levels of bone sialoprotein (BSP) 702:751 Knockdown of ppGalNAc-T1 or -T4 decreased mRNA and protein levels of bone sialoprotein (BSP). 27965094 4 26 theme ppGalNAc-T1 472:482 arg1 isoforms 492:499 ppGalNAc-T1 and -T4 isoforms 472:499 ppGalNAc-T1 and -T4 isoforms 472:499 We found that ppGalNAc-T1 and -T4 isoforms were highly expressed during osteogenesis of MC3T3-E1 and their knockdown by short hairpin RNA (shRNA) decreased osteoblast formation and bone mineralization. 27965094 2 27 from bone 305:308 arg1 abundant 289:296 abundant 289:296 abundant 289:296 Mucin-type O-glycoproteins are abundant in the bone and may play an important role in osteogenesis. 27965094 1 28 theme O-linked 226:233 arg1 glycosylation 243:255 O-linked protein glycosylation 226:255 O-linked protein glycosylation 226:255 The family of UDP-GalNAc polypeptide: N-Acetylgalactosaminlytransfersases (ppGalNAcTs) catalyzes the initial step of O-linked protein glycosylation. 27965094 0 29 theme osteogenic 31:40 arg1 factors 42:48 osteogenic factors 31:48 osteogenic factors 31:48 Isoform-specific regulation of osteogenic factors by polypeptide N-Acetylgalactosaminyltransferases 1 and 4. 27965094 7 30 theme ofppGalNAc-T4 854:866 arg1 isoform 868:874 Knockdown ofppGalNAc-T4 isoform 844:874 Knockdown ofppGalNAc-T4 isoform 844:874 Knockdown ofppGalNAc-T4 isoform decreased mRNA levels of OC, OPG and vitamin D receptor (VDR). 27965094 7 31 theme mRNA 886:889 arg1 levels 891:896 mRNA levels 886:896 mRNA levels of OC, OPG and vitamin D receptor (VDR) 886:936 Knockdown ofppGalNAc-T4 isoform decreased mRNA levels of OC, OPG and vitamin D receptor (VDR). 27965094 1 32 theme protein 235:241 arg1 glycosylation 243:255 O-linked protein glycosylation 226:255 O-linked protein glycosylation 226:255 The family of UDP-GalNAc polypeptide: N-Acetylgalactosaminlytransfersases (ppGalNAcTs) catalyzes the initial step of O-linked protein glycosylation. 27965094 4 33 theme osteoblast 614:623 arg1 formation 625:633 osteoblast formation 614:633 osteoblast formation 614:633 We found that ppGalNAc-T1 and -T4 isoforms were highly expressed during osteogenesis of MC3T3-E1 and their knockdown by short hairpin RNA (shRNA) decreased osteoblast formation and bone mineralization. 27965094 8 34 theme factor-κB 1066:1074 arg1 RANKL 1084:1088 RANKL 1084:1088 RANKL 1084:1088 While knockdown of T1 or T4 isoforms did not change the expression of osteopontin (OPN), COLLI, receptor activator for nuclear factor-κB ligand (RANKL) and transforming growth factor-β (TGF-β). 27965094 8 34 theme factor-κB 1066:1074 arg1 ligand 1076:1081 nuclear factor-κB ligand 1058:1081 nuclear factor-κB ligand (RANKL) 1058:1089 While knockdown of T1 or T4 isoforms did not change the expression of osteopontin (OPN), COLLI, receptor activator for nuclear factor-κB ligand (RANKL) and transforming growth factor-β (TGF-β). 27965094 3 35 from effects 382:388 arg1 osteogenesis 416:427 osteogenesis 416:427 osteogenesis of MC3T3-E1 pre-osteoblasts 416:455 Herein, we examined the effects of ppGalNAc-T isoforms on osteogenesis of MC3T3-E1 pre-osteoblasts. 27965094 1 36 theme UDP-GalNAc 123:132 arg1 polypeptide 134:144 UDP-GalNAc polypeptide 123:144 UDP-GalNAc polypeptide 123:144 The family of UDP-GalNAc polypeptide: N-Acetylgalactosaminlytransfersases (ppGalNAcTs) catalyzes the initial step of O-linked protein glycosylation. 27965094 1 37 theme glycosylation 243:255 arg1 step 218:221 the initial step 206:221 the initial step of O-linked protein glycosylation 206:255 The family of UDP-GalNAc polypeptide: N-Acetylgalactosaminlytransfersases (ppGalNAcTs) catalyzes the initial step of O-linked protein glycosylation. 27965094 7 38 theme OPG 905:907 arg1 levels 891:896 mRNA levels 886:896 mRNA levels of OC, OPG and vitamin D receptor (VDR) 886:936 Knockdown ofppGalNAc-T4 isoform decreased mRNA levels of OC, OPG and vitamin D receptor (VDR). 27965094 0 39 theme factors 42:48 arg1 regulation 17:26 Isoform-specific regulation 0:26 Isoform-specific regulation of osteogenic factors by polypeptide N-Acetylgalactosaminyltransferases 1 and 4. 0:107 Isoform-specific regulation of osteogenic factors by polypeptide N-Acetylgalactosaminyltransferases 1 and 4. 27965094 4 40 theme hairpin 584:590 arg1 RNA 592:594 short hairpin RNA 578:594 short hairpin RNA (shRNA) 578:602 We found that ppGalNAc-T1 and -T4 isoforms were highly expressed during osteogenesis of MC3T3-E1 and their knockdown by short hairpin RNA (shRNA) decreased osteoblast formation and bone mineralization. 27965094 4 40 theme hairpin 584:590 arg1 shRNA 597:601 shRNA 597:601 shRNA 597:601 We found that ppGalNAc-T1 and -T4 isoforms were highly expressed during osteogenesis of MC3T3-E1 and their knockdown by short hairpin RNA (shRNA) decreased osteoblast formation and bone mineralization. 27965094 10 41 theme different 1324:1332 arg1 factors 1345:1351 different osteogenic factors 1324:1351 different osteogenic factors 1324:1351 We also found that ppGalNAc-T1 and -T4 affected the expression of different osteogenic factors, suggesting distinct roles ppGalNAc-T isoformsplay in regulating osteogenesis in vitro. 27965094 3 42 theme pre-osteoblasts 441:455 arg1 osteogenesis 416:427 osteogenesis 416:427 osteogenesis of MC3T3-E1 pre-osteoblasts 416:455 Herein, we examined the effects of ppGalNAc-T isoforms on osteogenesis of MC3T3-E1 pre-osteoblasts. 27965094 4 43 theme short 578:582 arg1 RNA 592:594 short hairpin RNA 578:594 short hairpin RNA (shRNA) 578:602 We found that ppGalNAc-T1 and -T4 isoforms were highly expressed during osteogenesis of MC3T3-E1 and their knockdown by short hairpin RNA (shRNA) decreased osteoblast formation and bone mineralization. 27965094 4 43 theme short 578:582 arg1 shRNA 597:601 shRNA 597:601 shRNA 597:601 We found that ppGalNAc-T1 and -T4 isoforms were highly expressed during osteogenesis of MC3T3-E1 and their knockdown by short hairpin RNA (shRNA) decreased osteoblast formation and bone mineralization. 27965094 5 44 theme bone 729:732 arg1 BSP 748:750 BSP 748:750 BSP 748:750 Knockdown of ppGalNAc-T1 or -T4 decreased mRNA and protein levels of bone sialoprotein (BSP). 27965094 5 44 theme bone 729:732 arg1 sialoprotein 734:745 bone sialoprotein 729:745 bone sialoprotein (BSP) 729:751 Knockdown of ppGalNAc-T1 or -T4 decreased mRNA and protein levels of bone sialoprotein (BSP). 27965094 1 45 theme polypeptide 134:144 arg1 family 113:118 The family 109:118 The family of UDP-GalNAc polypeptide: N-Acetylgalactosaminlytransfersases (ppGalNAcTs) 109:194 The family of UDP-GalNAc polypeptide: N-Acetylgalactosaminlytransfersases (ppGalNAcTs) catalyzes the initial step of O-linked protein glycosylation. 27965094 0 46 theme polypeptide 53:63 arg1 N-Acetylgalactosaminyltransferases 65:98 polypeptide N-Acetylgalactosaminyltransferases 1 and 4 53:106 N-Acetylgalactosaminyltransferases 65:98 Isoform-specific regulation of osteogenic factors by polypeptide N-Acetylgalactosaminyltransferases 1 and 4. 27965094 5 47 theme sialoprotein 734:745 arg1 levels 719:724 mRNA and protein levels 702:724 mRNA and protein levels of bone sialoprotein (BSP) 702:751 Knockdown of ppGalNAc-T1 or -T4 decreased mRNA and protein levels of bone sialoprotein (BSP). 27965094 2 48 theme Mucin-type 258:267 arg1 O-glycoproteins 269:283 Mucin-type O-glycoproteins 258:283 Mucin-type O-glycoproteins 258:283 Mucin-type O-glycoproteins are abundant in the bone and may play an important role in osteogenesis. 27965094 5 49 theme -T4 688:690 arg1 Knockdown 660:668 Knockdown 660:668 Knockdown of ppGalNAc-T1 or -T4 660:690 Knockdown of ppGalNAc-T1 or -T4 decreased mRNA and protein levels of bone sialoprotein (BSP). 27965094 8 50 theme T1 958:959 arg1 isoforms 967:974 T1 or T4 isoforms 958:974 T1 or T4 isoforms 958:974 While knockdown of T1 or T4 isoforms did not change the expression of osteopontin (OPN), COLLI, receptor activator for nuclear factor-κB ligand (RANKL) and transforming growth factor-β (TGF-β). 27965094 8 51 theme receptor 1035:1042 arg1 COLLI 1028:1032 COLLI 1028:1032 COLLI 1028:1032 While knockdown of T1 or T4 isoforms did not change the expression of osteopontin (OPN), COLLI, receptor activator for nuclear factor-κB ligand (RANKL) and transforming growth factor-β (TGF-β). 27965094 8 51 theme receptor 1035:1042 arg1 activator 1044:1052 receptor activator 1035:1052 receptor activator for nuclear factor-κB ligand (RANKL) and transforming growth factor-β (TGF-β) 1035:1130 While knockdown of T1 or T4 isoforms did not change the expression of osteopontin (OPN), COLLI, receptor activator for nuclear factor-κB ligand (RANKL) and transforming growth factor-β (TGF-β). 27965094 9 52 theme MC3T3-E1 1203:1210 arg1 cells 1212:1216 MC3T3-E1 cells 1203:1216 MC3T3-E1 cells 1203:1216 Our results demonstrated that the ppGalNAc-T4 was highly expressed in MC3T3-E1 cells during osteogenesis for the first time. 27965094 8 53 theme growth 1108:1113 arg1 TGF-β 1125:1129 TGF-β 1125:1129 TGF-β 1125:1129 While knockdown of T1 or T4 isoforms did not change the expression of osteopontin (OPN), COLLI, receptor activator for nuclear factor-κB ligand (RANKL) and transforming growth factor-β (TGF-β). 27965094 8 53 theme growth 1108:1113 arg1 factor-β 1115:1122 transforming growth factor-β 1095:1122 transforming growth factor-β (TGF-β) 1095:1130 While knockdown of T1 or T4 isoforms did not change the expression of osteopontin (OPN), COLLI, receptor activator for nuclear factor-κB ligand (RANKL) and transforming growth factor-β (TGF-β). 27965094 9 54 theme first 1246:1250 arg1 time 1252:1255 the first time 1242:1255 the first time 1242:1255 Our results demonstrated that the ppGalNAc-T4 was highly expressed in MC3T3-E1 cells during osteogenesis for the first time. 27965094 6 55 theme osteocalcin 803:813 arg1 levels 793:798 ppGalNAc-T1decreased mRNA levels 767:798 ppGalNAc-T1decreased mRNA levels of osteocalcin (OC), osteoprotegerin (OPG) 767:841 Knockdown of ppGalNAc-T1decreased mRNA levels of osteocalcin (OC), osteoprotegerin (OPG). 27965094 10 56 theme factors 1345:1351 arg1 expression 1310:1319 the expression 1306:1319 the expression of different osteogenic factors 1306:1351 We also found that ppGalNAc-T1 and -T4 affected the expression of different osteogenic factors, suggesting distinct roles ppGalNAc-T isoformsplay in regulating osteogenesis in vitro. 27965094 8 57 theme transforming 1095:1106 arg1 TGF-β 1125:1129 TGF-β 1125:1129 TGF-β 1125:1129 While knockdown of T1 or T4 isoforms did not change the expression of osteopontin (OPN), COLLI, receptor activator for nuclear factor-κB ligand (RANKL) and transforming growth factor-β (TGF-β). 27965094 8 57 theme transforming 1095:1106 arg1 factor-β 1115:1122 transforming growth factor-β 1095:1122 transforming growth factor-β (TGF-β) 1095:1130 While knockdown of T1 or T4 isoforms did not change the expression of osteopontin (OPN), COLLI, receptor activator for nuclear factor-κB ligand (RANKL) and transforming growth factor-β (TGF-β). 27965094 4 58 theme -T4 488:490 arg1 isoforms 492:499 ppGalNAc-T1 and -T4 isoforms 472:499 ppGalNAc-T1 and -T4 isoforms 472:499 We found that ppGalNAc-T1 and -T4 isoforms were highly expressed during osteogenesis of MC3T3-E1 and their knockdown by short hairpin RNA (shRNA) decreased osteoblast formation and bone mineralization. 27965094 8 59 theme T4 964:965 arg1 isoforms 967:974 T1 or T4 isoforms 958:974 T1 or T4 isoforms 958:974 While knockdown of T1 or T4 isoforms did not change the expression of osteopontin (OPN), COLLI, receptor activator for nuclear factor-κB ligand (RANKL) and transforming growth factor-β (TGF-β). 27965094 6 60 theme levels 793:798 arg1 Knockdown 754:762 Knockdown 754:762 Knockdown of ppGalNAc-T1decreased mRNA levels of osteocalcin (OC), osteoprotegerin (OPG). 754:842 Knockdown of ppGalNAc-T1decreased mRNA levels of osteocalcin (OC), osteoprotegerin (OPG). 27965094 2 61 gly O-glycoproteins 269:283 arg1 O-glycoproteins 269:283 Mucin-type O-glycoproteins 258:283 Mucin-type O-glycoproteins 258:283 Mucin-type O-glycoproteins are abundant in the bone and may play an important role in osteogenesis. 27965094 6 62 theme mRNA 788:791 arg1 levels 793:798 ppGalNAc-T1decreased mRNA levels 767:798 ppGalNAc-T1decreased mRNA levels of osteocalcin (OC), osteoprotegerin (OPG) 767:841 Knockdown of ppGalNAc-T1decreased mRNA levels of osteocalcin (OC), osteoprotegerin (OPG). 27965094 7 63 theme D 921:921 arg1 VDR 933:935 VDR 933:935 VDR 933:935 Knockdown ofppGalNAc-T4 isoform decreased mRNA levels of OC, OPG and vitamin D receptor (VDR). 27965094 7 63 theme D 921:921 arg1 receptor 923:930 vitamin D receptor 913:930 vitamin D receptor (VDR) 913:936 Knockdown ofppGalNAc-T4 isoform decreased mRNA levels of OC, OPG and vitamin D receptor (VDR). 27847504 8 0 theme sixth 1192:1196 arg1 deoxyhexose 1254:1264 a putative dimethylated deoxyhexose 1230:1264 a putative dimethylated deoxyhexose 1230:1264 The sixth monosaccharide in the glycan is a putative dimethylated deoxyhexose. 27847504 8 0 theme sixth 1192:1196 arg1 monosaccharide 1198:1211 The sixth monosaccharide 1188:1211 The sixth monosaccharide in the glycan 1188:1225 The sixth monosaccharide in the glycan is a putative dimethylated deoxyhexose. 27847504 7 1 theme residues 1147:1154 arg1 GalNAc 1180:1185 GalNAc 1180:1185 GalNAc 1180:1185 Four of these HexNAc residues have been identified as GalNAc. 27847504 7 1 theme residues 1147:1154 arg1 residues 1147:1154 these HexNAc residues 1134:1154 these HexNAc residues 1134:1154 Four of these HexNAc residues have been identified as GalNAc. 27847504 7 1 theme residues 1147:1154 arg1 Four 1126:1129 Four 1126:1129 Four 1126:1129 Four of these HexNAc residues have been identified as GalNAc. 27847504 3 2 from studies 546:552 arg1 results 533:539 Previous results 524:539 Previous results from studies with the model anammox organism Kuenenia stuttgartiensis 524:609 Previous results from studies with the model anammox organism Kuenenia stuttgartiensis suggested that the protein monomers building the S-layer lattice are glycosylated. 27847504 1 3 theme dinitrogen 266:275 arg1 gas 277:279 dinitrogen gas 266:279 dinitrogen gas 266:279 Anaerobic ammonium oxidation (anammox) bacteria are a distinct group of Planctomycetes that are characterized by their unique ability to perform anammox with nitrite to dinitrogen gas in a specialized organelle. 27847504 3 4 theme model 563:567 arg1 organism 577:584 the model anammox organism 559:584 the model anammox organism Kuenenia stuttgartiensis 559:609 Previous results from studies with the model anammox organism Kuenenia stuttgartiensis suggested that the protein monomers building the S-layer lattice are glycosylated. 27847504 1 5 theme Planctomycetes 169:182 arg1 bacteria 136:143 Anaerobic ammonium oxidation (anammox) bacteria 97:143 Anaerobic ammonium oxidation (anammox) bacteria 97:143 Anaerobic ammonium oxidation (anammox) bacteria are a distinct group of Planctomycetes that are characterized by their unique ability to perform anammox with nitrite to dinitrogen gas in a specialized organelle. 27847504 1 5 theme Planctomycetes 169:182 arg1 Planctomycetes 169:182 Planctomycetes 169:182 Planctomycetes 169:182 Anaerobic ammonium oxidation (anammox) bacteria are a distinct group of Planctomycetes that are characterized by their unique ability to perform anammox with nitrite to dinitrogen gas in a specialized organelle. 27847504 1 5 theme Planctomycetes 169:182 arg1 group 160:164 a distinct group 149:164 a distinct group of Planctomycetes that are characterized by their unique ability to perform anammox with nitrite to dinitrogen gas in a specialized organelle 149:306 Anaerobic ammonium oxidation (anammox) bacteria are a distinct group of Planctomycetes that are characterized by their unique ability to perform anammox with nitrite to dinitrogen gas in a specialized organelle. 27847504 11 6 theme abiotic 1851:1857 arg1 surfaces 1859:1866 abiotic surfaces 1851:1866 abiotic surfaces 1851:1866 S-layer glycosylation clearly contributes to the diversification of the K. stuttgartiensis cell surface and can be expected to influence the interaction of the bacterium with other cells or abiotic surfaces. 27847504 5 7 theme 1591-amino 981:990 arg1 protein 1005:1011 the entire 1591-amino acid S-layer protein 970:1011 the entire 1591-amino acid S-layer protein 970:1011 Mass spectrometry (MS) analysis showed an O-glycan attached to 13 sites distributed over the entire 1591-amino acid S-layer protein. 27847504 5 8 theme spectrometry 886:897 arg1 analysis 904:911 Mass spectrometry (MS) analysis 881:911 Mass spectrometry (MS) analysis 881:911 Mass spectrometry (MS) analysis showed an O-glycan attached to 13 sites distributed over the entire 1591-amino acid S-layer protein. 27847504 8 9 theme dimethylated 1241:1252 arg1 monosaccharide 1198:1211 The sixth monosaccharide 1188:1211 The sixth monosaccharide in the glycan 1188:1225 The sixth monosaccharide in the glycan is a putative dimethylated deoxyhexose. 27847504 8 9 theme dimethylated 1241:1252 arg1 deoxyhexose 1254:1264 a putative dimethylated deoxyhexose 1230:1264 a putative dimethylated deoxyhexose 1230:1264 The sixth monosaccharide in the glycan is a putative dimethylated deoxyhexose. 27847504 1 10 theme unique 216:221 arg1 ability 223:229 their unique ability to perform anammox with nitrite to dinitrogen gas in a specialized organelle 210:306 their unique ability to perform anammox with nitrite to dinitrogen gas in a specialized organelle 210:306 Anaerobic ammonium oxidation (anammox) bacteria are a distinct group of Planctomycetes that are characterized by their unique ability to perform anammox with nitrite to dinitrogen gas in a specialized organelle. 27847504 9 11 theme residues 1285:1292 arg1 Two 1267:1269 Two 1267:1269 Two 1267:1269 Two of the HexNAc residues were also found to contain a methyl group, thereby leading to an extensive degree of methylation of the glycan. 27847504 9 11 theme residues 1285:1292 arg1 residues 1285:1292 the HexNAc residues 1274:1292 the HexNAc residues 1274:1292 Two of the HexNAc residues were also found to contain a methyl group, thereby leading to an extensive degree of methylation of the glycan. 27847504 3 12 theme protein 630:636 arg1 monomers 638:645 the protein monomers 626:645 the protein monomers building the S-layer lattice 626:674 Previous results from studies with the model anammox organism Kuenenia stuttgartiensis suggested that the protein monomers building the S-layer lattice are glycosylated. 27847504 1 13 theme anammox 127:133 arg1 bacteria 136:143 Anaerobic ammonium oxidation (anammox) bacteria 97:143 Anaerobic ammonium oxidation (anammox) bacteria 97:143 Anaerobic ammonium oxidation (anammox) bacteria are a distinct group of Planctomycetes that are characterized by their unique ability to perform anammox with nitrite to dinitrogen gas in a specialized organelle. 27847504 1 13 theme anammox 127:133 arg1 Planctomycetes 169:182 Planctomycetes 169:182 Planctomycetes 169:182 Anaerobic ammonium oxidation (anammox) bacteria are a distinct group of Planctomycetes that are characterized by their unique ability to perform anammox with nitrite to dinitrogen gas in a specialized organelle. 27847504 1 13 theme anammox 127:133 arg1 group 160:164 a distinct group 149:164 a distinct group of Planctomycetes that are characterized by their unique ability to perform anammox with nitrite to dinitrogen gas in a specialized organelle 149:306 Anaerobic ammonium oxidation (anammox) bacteria are a distinct group of Planctomycetes that are characterized by their unique ability to perform anammox with nitrite to dinitrogen gas in a specialized organelle. 27847504 4 14 theme protein 767:773 arg1 glycosylation 775:787 the S-layer protein glycosylation 755:787 the S-layer protein glycosylation 755:787 In the present study, we focussed on the characterization of the S-layer protein glycosylation in order to increase our knowledge on the cell surface characteristics of anammox bacteria. 27847504 1 15 theme ammonium 107:114 arg1 bacteria 136:143 Anaerobic ammonium oxidation (anammox) bacteria 97:143 Anaerobic ammonium oxidation (anammox) bacteria 97:143 Anaerobic ammonium oxidation (anammox) bacteria are a distinct group of Planctomycetes that are characterized by their unique ability to perform anammox with nitrite to dinitrogen gas in a specialized organelle. 27847504 1 15 theme ammonium 107:114 arg1 Planctomycetes 169:182 Planctomycetes 169:182 Planctomycetes 169:182 Anaerobic ammonium oxidation (anammox) bacteria are a distinct group of Planctomycetes that are characterized by their unique ability to perform anammox with nitrite to dinitrogen gas in a specialized organelle. 27847504 1 15 theme ammonium 107:114 arg1 group 160:164 a distinct group 149:164 a distinct group of Planctomycetes that are characterized by their unique ability to perform anammox with nitrite to dinitrogen gas in a specialized organelle 149:306 Anaerobic ammonium oxidation (anammox) bacteria are a distinct group of Planctomycetes that are characterized by their unique ability to perform anammox with nitrite to dinitrogen gas in a specialized organelle. 27847504 10 16 attach presents 1417:1424 arg1 planctomycete 1476:1488 planctomycete 1476:1488 planctomycete 1476:1488 This study presents the first characterization of a glycoprotein in a planctomycete and shows that the S-layer protein Kustd1514 of K. stuttgartiensis is heavily glycosylated with an O-linked oligosaccharide which is additionally modified by methylation. 27847504 10 16 attach presents 1417:1424 arg2 study 1411:1415 This study 1406:1415 This study 1406:1415 This study presents the first characterization of a glycoprotein in a planctomycete and shows that the S-layer protein Kustd1514 of K. stuttgartiensis is heavily glycosylated with an O-linked oligosaccharide which is additionally modified by methylation. 27847504 0 17 theme stuttgartiensis 54:68 arg1 Protein 12:18 The S-Layer Protein 0:18 The S-Layer Protein of the Anammox Bacterium Kuenenia stuttgartiensis 0:68 The S-Layer Protein of the Anammox Bacterium Kuenenia stuttgartiensis Is Heavily O-Glycosylated. 27847504 0 17 theme stuttgartiensis 54:68 arg1 O-Glycosylated 81:94 O-Glycosylated 81:94 O-Glycosylated 81:94 The S-Layer Protein of the Anammox Bacterium Kuenenia stuttgartiensis Is Heavily O-Glycosylated. 27847504 3 18 theme S-layer 660:666 arg1 lattice 668:674 the S-layer lattice 656:674 the S-layer lattice 656:674 Previous results from studies with the model anammox organism Kuenenia stuttgartiensis suggested that the protein monomers building the S-layer lattice are glycosylated. 27847504 11 19 with interaction 1802:1812 arg1 cells 1842:1846 other cells 1836:1846 other cells 1836:1846 S-layer glycosylation clearly contributes to the diversification of the K. stuttgartiensis cell surface and can be expected to influence the interaction of the bacterium with other cells or abiotic surfaces. 27847504 11 19 with interaction 1802:1812 arg1 surfaces 1859:1866 abiotic surfaces 1851:1866 abiotic surfaces 1851:1866 S-layer glycosylation clearly contributes to the diversification of the K. stuttgartiensis cell surface and can be expected to influence the interaction of the bacterium with other cells or abiotic surfaces. 27847504 6 20 theme monosaccharide 1045:1058 arg1 residues 1060:1067 six monosaccharide residues 1041:1067 six monosaccharide residues 1041:1067 This glycan is composed of six monosaccharide residues, of which five are N-acetylhexosamine (HexNAc) residues. 27847504 1 21 theme oxidation 116:124 arg1 bacteria 136:143 Anaerobic ammonium oxidation (anammox) bacteria 97:143 Anaerobic ammonium oxidation (anammox) bacteria 97:143 Anaerobic ammonium oxidation (anammox) bacteria are a distinct group of Planctomycetes that are characterized by their unique ability to perform anammox with nitrite to dinitrogen gas in a specialized organelle. 27847504 1 21 theme oxidation 116:124 arg1 Planctomycetes 169:182 Planctomycetes 169:182 Planctomycetes 169:182 Anaerobic ammonium oxidation (anammox) bacteria are a distinct group of Planctomycetes that are characterized by their unique ability to perform anammox with nitrite to dinitrogen gas in a specialized organelle. 27847504 1 21 theme oxidation 116:124 arg1 group 160:164 a distinct group 149:164 a distinct group of Planctomycetes that are characterized by their unique ability to perform anammox with nitrite to dinitrogen gas in a specialized organelle 149:306 Anaerobic ammonium oxidation (anammox) bacteria are a distinct group of Planctomycetes that are characterized by their unique ability to perform anammox with nitrite to dinitrogen gas in a specialized organelle. 27847504 1 22 theme Anaerobic 97:105 arg1 bacteria 136:143 Anaerobic ammonium oxidation (anammox) bacteria 97:143 Anaerobic ammonium oxidation (anammox) bacteria 97:143 Anaerobic ammonium oxidation (anammox) bacteria are a distinct group of Planctomycetes that are characterized by their unique ability to perform anammox with nitrite to dinitrogen gas in a specialized organelle. 27847504 1 22 theme Anaerobic 97:105 arg1 Planctomycetes 169:182 Planctomycetes 169:182 Planctomycetes 169:182 Anaerobic ammonium oxidation (anammox) bacteria are a distinct group of Planctomycetes that are characterized by their unique ability to perform anammox with nitrite to dinitrogen gas in a specialized organelle. 27847504 1 22 theme Anaerobic 97:105 arg1 group 160:164 a distinct group 149:164 a distinct group of Planctomycetes that are characterized by their unique ability to perform anammox with nitrite to dinitrogen gas in a specialized organelle 149:306 Anaerobic ammonium oxidation (anammox) bacteria are a distinct group of Planctomycetes that are characterized by their unique ability to perform anammox with nitrite to dinitrogen gas in a specialized organelle. 27847504 2 23 theme direct 458:463 arg1 zone 477:480 the direct interaction zone 454:480 the direct interaction zone of anammox bacteria with the environment 454:521 The cell of anammox bacteria comprises three membrane-bound compartments and is surrounded by a two-dimensional crystalline S-layer representing the direct interaction zone of anammox bacteria with the environment. 27847504 10 24 theme protein 1517:1523 arg1 Kustd1514 1525:1533 the S-layer protein Kustd1514 1505:1533 the S-layer protein Kustd1514 of K. stuttgartiensis 1505:1555 This study presents the first characterization of a glycoprotein in a planctomycete and shows that the S-layer protein Kustd1514 of K. stuttgartiensis is heavily glycosylated with an O-linked oligosaccharide which is additionally modified by methylation. 27847504 9 25 theme extensive 1359:1367 arg1 degree 1369:1374 an extensive degree 1356:1374 an extensive degree of methylation of the glycan 1356:1403 Two of the HexNAc residues were also found to contain a methyl group, thereby leading to an extensive degree of methylation of the glycan. 27847504 5 26 theme S-layer 997:1003 arg1 protein 1005:1011 the entire 1591-amino acid S-layer protein 970:1011 the entire 1591-amino acid S-layer protein 970:1011 Mass spectrometry (MS) analysis showed an O-glycan attached to 13 sites distributed over the entire 1591-amino acid S-layer protein. 27847504 4 27 theme anammox 863:869 arg1 bacteria 871:878 anammox bacteria 863:878 anammox bacteria 863:878 In the present study, we focussed on the characterization of the S-layer protein glycosylation in order to increase our knowledge on the cell surface characteristics of anammox bacteria. 27847504 2 28 theme crystalline 421:431 arg1 S-layer 433:439 a two-dimensional crystalline S-layer 403:439 a two-dimensional crystalline S-layer representing the direct interaction zone of anammox bacteria with the environment 403:521 The cell of anammox bacteria comprises three membrane-bound compartments and is surrounded by a two-dimensional crystalline S-layer representing the direct interaction zone of anammox bacteria with the environment. 27847504 2 29 theme anammox 485:491 arg1 bacteria 493:500 anammox bacteria 485:500 anammox bacteria with the environment 485:521 The cell of anammox bacteria comprises three membrane-bound compartments and is surrounded by a two-dimensional crystalline S-layer representing the direct interaction zone of anammox bacteria with the environment. 27847504 10 30 theme stuttgartiensis 1541:1555 arg1 Kustd1514 1525:1533 the S-layer protein Kustd1514 1505:1533 the S-layer protein Kustd1514 of K. stuttgartiensis 1505:1555 This study presents the first characterization of a glycoprotein in a planctomycete and shows that the S-layer protein Kustd1514 of K. stuttgartiensis is heavily glycosylated with an O-linked oligosaccharide which is additionally modified by methylation. 27847504 11 31 theme cell 1752:1755 arg1 surface 1757:1763 the K. stuttgartiensis cell surface 1729:1763 the K. stuttgartiensis cell surface 1729:1763 S-layer glycosylation clearly contributes to the diversification of the K. stuttgartiensis cell surface and can be expected to influence the interaction of the bacterium with other cells or abiotic surfaces. 27847504 0 32 theme Bacterium 35:43 arg1 stuttgartiensis 54:68 the Anammox Bacterium Kuenenia stuttgartiensis 23:68 the Anammox Bacterium Kuenenia stuttgartiensis 23:68 The S-Layer Protein of the Anammox Bacterium Kuenenia stuttgartiensis Is Heavily O-Glycosylated. 27847504 4 33 theme cell 831:834 arg1 characteristics 844:858 the cell surface characteristics 827:858 the cell surface characteristics of anammox bacteria 827:878 In the present study, we focussed on the characterization of the S-layer protein glycosylation in order to increase our knowledge on the cell surface characteristics of anammox bacteria. 27847504 2 34 theme anammox 321:327 arg1 bacteria 329:336 anammox bacteria 321:336 anammox bacteria 321:336 The cell of anammox bacteria comprises three membrane-bound compartments and is surrounded by a two-dimensional crystalline S-layer representing the direct interaction zone of anammox bacteria with the environment. 27847504 9 35 theme glycan 1398:1403 arg1 methylation 1379:1389 methylation 1379:1389 methylation of the glycan 1379:1403 Two of the HexNAc residues were also found to contain a methyl group, thereby leading to an extensive degree of methylation of the glycan. 27847504 7 36 theme HexNAc 1140:1145 arg1 residues 1147:1154 these HexNAc residues 1134:1154 these HexNAc residues 1134:1154 Four of these HexNAc residues have been identified as GalNAc. 27847504 10 37 gly glycoprotein 1458:1469 arg1 glycoprotein 1458:1469 a glycoprotein 1456:1469 a glycoprotein 1456:1469 This study presents the first characterization of a glycoprotein in a planctomycete and shows that the S-layer protein Kustd1514 of K. stuttgartiensis is heavily glycosylated with an O-linked oligosaccharide which is additionally modified by methylation. 27847504 2 38 theme membrane-bound 354:367 arg1 compartments 369:380 three membrane-bound compartments 348:380 three membrane-bound compartments 348:380 The cell of anammox bacteria comprises three membrane-bound compartments and is surrounded by a two-dimensional crystalline S-layer representing the direct interaction zone of anammox bacteria with the environment. 27847504 3 39 with studies 546:552 arg1 organism 577:584 the model anammox organism 559:584 the model anammox organism Kuenenia stuttgartiensis 559:609 Previous results from studies with the model anammox organism Kuenenia stuttgartiensis suggested that the protein monomers building the S-layer lattice are glycosylated. 27847504 3 40 theme anammox 569:575 arg1 organism 577:584 the model anammox organism 559:584 the model anammox organism Kuenenia stuttgartiensis 559:609 Previous results from studies with the model anammox organism Kuenenia stuttgartiensis suggested that the protein monomers building the S-layer lattice are glycosylated. 27847504 5 41 attach attached 932:939 arg2 O-glycan 923:930 an O-glycan 920:930 an O-glycan attached to 13 sites distributed over the entire 1591-amino acid S-layer protein 920:1011 Mass spectrometry (MS) analysis showed an O-glycan attached to 13 sites distributed over the entire 1591-amino acid S-layer protein. 27847504 5 41 attach attached 932:939 arg1 sites 947:951 13 sites 944:951 13 sites distributed over the entire 1591-amino acid S-layer protein 944:1011 Mass spectrometry (MS) analysis showed an O-glycan attached to 13 sites distributed over the entire 1591-amino acid S-layer protein. 27847504 3 42 gly glycosylated 680:691 arg1 monomers 638:645 the protein monomers 626:645 the protein monomers building the S-layer lattice 626:674 Previous results from studies with the model anammox organism Kuenenia stuttgartiensis suggested that the protein monomers building the S-layer lattice are glycosylated. 27847504 10 43 theme O-linked 1589:1596 arg1 oligosaccharide 1598:1612 an O-linked oligosaccharide 1586:1612 an O-linked oligosaccharide which is additionally modified by methylation 1586:1658 This study presents the first characterization of a glycoprotein in a planctomycete and shows that the S-layer protein Kustd1514 of K. stuttgartiensis is heavily glycosylated with an O-linked oligosaccharide which is additionally modified by methylation. 27847504 11 44 theme K. 1733:1734 arg1 surface 1757:1763 the K. stuttgartiensis cell surface 1729:1763 the K. stuttgartiensis cell surface 1729:1763 S-layer glycosylation clearly contributes to the diversification of the K. stuttgartiensis cell surface and can be expected to influence the interaction of the bacterium with other cells or abiotic surfaces. 27847504 4 45 theme present 701:707 arg1 study 709:713 the present study 697:713 the present study 697:713 In the present study, we focussed on the characterization of the S-layer protein glycosylation in order to increase our knowledge on the cell surface characteristics of anammox bacteria. 27847504 10 46 theme first 1430:1434 arg1 characterization 1436:1451 the first characterization 1426:1451 the first characterization of a glycoprotein 1426:1469 This study presents the first characterization of a glycoprotein in a planctomycete and shows that the S-layer protein Kustd1514 of K. stuttgartiensis is heavily glycosylated with an O-linked oligosaccharide which is additionally modified by methylation. 27847504 3 47 theme Kuenenia 586:593 arg1 organism 577:584 the model anammox organism 559:584 the model anammox organism Kuenenia stuttgartiensis 559:609 Previous results from studies with the model anammox organism Kuenenia stuttgartiensis suggested that the protein monomers building the S-layer lattice are glycosylated. 27847504 5 48 theme Mass 881:884 arg1 MS 900:901 MS 900:901 MS 900:901 Mass spectrometry (MS) analysis showed an O-glycan attached to 13 sites distributed over the entire 1591-amino acid S-layer protein. 27847504 5 48 theme Mass 881:884 arg1 spectrometry 886:897 Mass spectrometry 881:897 Mass spectrometry (MS) analysis 881:911 Mass spectrometry (MS) analysis showed an O-glycan attached to 13 sites distributed over the entire 1591-amino acid S-layer protein. 27847504 3 49 theme Previous 524:531 arg1 results 533:539 Previous results 524:539 Previous results from studies with the model anammox organism Kuenenia stuttgartiensis 524:609 Previous results from studies with the model anammox organism Kuenenia stuttgartiensis suggested that the protein monomers building the S-layer lattice are glycosylated. 27847504 8 50 theme putative 1232:1239 arg1 monosaccharide 1198:1211 The sixth monosaccharide 1188:1211 The sixth monosaccharide in the glycan 1188:1225 The sixth monosaccharide in the glycan is a putative dimethylated deoxyhexose. 27847504 8 50 theme putative 1232:1239 arg1 deoxyhexose 1254:1264 a putative dimethylated deoxyhexose 1230:1264 a putative dimethylated deoxyhexose 1230:1264 The sixth monosaccharide in the glycan is a putative dimethylated deoxyhexose. 27847504 9 51 theme HexNAc 1278:1283 arg1 residues 1285:1292 the HexNAc residues 1274:1292 the HexNAc residues 1274:1292 Two of the HexNAc residues were also found to contain a methyl group, thereby leading to an extensive degree of methylation of the glycan. 27847504 10 52 gly glycosylated 1568:1579 arg1 Kustd1514 1525:1533 the S-layer protein Kustd1514 1505:1533 the S-layer protein Kustd1514 of K. stuttgartiensis 1505:1555 This study presents the first characterization of a glycoprotein in a planctomycete and shows that the S-layer protein Kustd1514 of K. stuttgartiensis is heavily glycosylated with an O-linked oligosaccharide which is additionally modified by methylation. 27847504 4 53 theme S-layer 759:765 arg1 glycosylation 775:787 the S-layer protein glycosylation 755:787 the S-layer protein glycosylation 755:787 In the present study, we focussed on the characterization of the S-layer protein glycosylation in order to increase our knowledge on the cell surface characteristics of anammox bacteria. 27847504 3 54 dep Kuenenia 586:593 arg1 stuttgartiensis 595:609 stuttgartiensis 595:609 stuttgartiensis 595:609 Previous results from studies with the model anammox organism Kuenenia stuttgartiensis suggested that the protein monomers building the S-layer lattice are glycosylated. 27847504 6 55 theme residues 1060:1067 arg1 residues 1060:1067 six monosaccharide residues 1041:1067 six monosaccharide residues 1041:1067 This glycan is composed of six monosaccharide residues, of which five are N-acetylhexosamine (HexNAc) residues. 27847504 6 55 theme residues 1060:1067 arg1 five 1079:1082 five 1079:1082 five 1079:1082 This glycan is composed of six monosaccharide residues, of which five are N-acetylhexosamine (HexNAc) residues. 27847504 6 55 theme residues 1060:1067 arg1 residues 1116:1123 N-acetylhexosamine (HexNAc) residues 1088:1123 N-acetylhexosamine (HexNAc) residues 1088:1123 This glycan is composed of six monosaccharide residues, of which five are N-acetylhexosamine (HexNAc) residues. 27847504 10 56 mod modified 1636:1643 arg3 methylation 1648:1658 methylation 1648:1658 methylation 1648:1658 This study presents the first characterization of a glycoprotein in a planctomycete and shows that the S-layer protein Kustd1514 of K. stuttgartiensis is heavily glycosylated with an O-linked oligosaccharide which is additionally modified by methylation. 27847504 10 56 mod modified 1636:1643 arg1 oligosaccharide 1598:1612 an O-linked oligosaccharide 1586:1612 an O-linked oligosaccharide which is additionally modified by methylation 1586:1658 This study presents the first characterization of a glycoprotein in a planctomycete and shows that the S-layer protein Kustd1514 of K. stuttgartiensis is heavily glycosylated with an O-linked oligosaccharide which is additionally modified by methylation. 27847504 2 57 with bacteria 493:500 arg1 environment 511:521 the environment 507:521 the environment 507:521 The cell of anammox bacteria comprises three membrane-bound compartments and is surrounded by a two-dimensional crystalline S-layer representing the direct interaction zone of anammox bacteria with the environment. 27847504 1 58 theme distinct 151:158 arg1 bacteria 136:143 Anaerobic ammonium oxidation (anammox) bacteria 97:143 Anaerobic ammonium oxidation (anammox) bacteria 97:143 Anaerobic ammonium oxidation (anammox) bacteria are a distinct group of Planctomycetes that are characterized by their unique ability to perform anammox with nitrite to dinitrogen gas in a specialized organelle. 27847504 1 58 theme distinct 151:158 arg1 Planctomycetes 169:182 Planctomycetes 169:182 Planctomycetes 169:182 Anaerobic ammonium oxidation (anammox) bacteria are a distinct group of Planctomycetes that are characterized by their unique ability to perform anammox with nitrite to dinitrogen gas in a specialized organelle. 27847504 1 58 theme distinct 151:158 arg1 group 160:164 a distinct group 149:164 a distinct group of Planctomycetes that are characterized by their unique ability to perform anammox with nitrite to dinitrogen gas in a specialized organelle 149:306 Anaerobic ammonium oxidation (anammox) bacteria are a distinct group of Planctomycetes that are characterized by their unique ability to perform anammox with nitrite to dinitrogen gas in a specialized organelle. 27847504 10 59 theme glycoprotein 1458:1469 arg1 characterization 1436:1451 the first characterization 1426:1451 the first characterization of a glycoprotein 1426:1469 This study presents the first characterization of a glycoprotein in a planctomycete and shows that the S-layer protein Kustd1514 of K. stuttgartiensis is heavily glycosylated with an O-linked oligosaccharide which is additionally modified by methylation. 27847504 11 60 theme other 1836:1840 arg1 cells 1842:1846 other cells 1836:1846 other cells 1836:1846 S-layer glycosylation clearly contributes to the diversification of the K. stuttgartiensis cell surface and can be expected to influence the interaction of the bacterium with other cells or abiotic surfaces. 27847504 9 61 theme methyl 1323:1328 arg1 group 1330:1334 a methyl group 1321:1334 a methyl group 1321:1334 Two of the HexNAc residues were also found to contain a methyl group, thereby leading to an extensive degree of methylation of the glycan. 27847504 4 62 from knowledge 814:822 arg1 characteristics 844:858 the cell surface characteristics 827:858 the cell surface characteristics of anammox bacteria 827:878 In the present study, we focussed on the characterization of the S-layer protein glycosylation in order to increase our knowledge on the cell surface characteristics of anammox bacteria. 27847504 11 63 theme S-layer 1661:1667 arg1 glycosylation 1669:1681 S-layer glycosylation 1661:1681 S-layer glycosylation 1661:1681 S-layer glycosylation clearly contributes to the diversification of the K. stuttgartiensis cell surface and can be expected to influence the interaction of the bacterium with other cells or abiotic surfaces. 27847504 11 64 theme bacterium 1821:1829 arg1 interaction 1802:1812 the interaction 1798:1812 the interaction of the bacterium with other cells or abiotic surfaces 1798:1866 S-layer glycosylation clearly contributes to the diversification of the K. stuttgartiensis cell surface and can be expected to influence the interaction of the bacterium with other cells or abiotic surfaces. 27847504 9 65 contain contain 1313:1319 arg1 Two 1267:1269 Two 1267:1269 Two 1267:1269 Two of the HexNAc residues were also found to contain a methyl group, thereby leading to an extensive degree of methylation of the glycan. 27847504 9 65 contain contain 1313:1319 arg2 group 1330:1334 a methyl group 1321:1334 a methyl group 1321:1334 Two of the HexNAc residues were also found to contain a methyl group, thereby leading to an extensive degree of methylation of the glycan. 27847504 9 65 contain contain 1313:1319 arg1 residues 1285:1292 the HexNAc residues 1274:1292 the HexNAc residues 1274:1292 Two of the HexNAc residues were also found to contain a methyl group, thereby leading to an extensive degree of methylation of the glycan. 27847504 0 66 theme S-Layer 4:10 arg1 Protein 12:18 The S-Layer Protein 0:18 The S-Layer Protein of the Anammox Bacterium Kuenenia stuttgartiensis 0:68 The S-Layer Protein of the Anammox Bacterium Kuenenia stuttgartiensis Is Heavily O-Glycosylated. 27847504 0 66 theme S-Layer 4:10 arg1 O-Glycosylated 81:94 O-Glycosylated 81:94 O-Glycosylated 81:94 The S-Layer Protein of the Anammox Bacterium Kuenenia stuttgartiensis Is Heavily O-Glycosylated. 27847504 5 67 theme entire 974:979 arg1 protein 1005:1011 the entire 1591-amino acid S-layer protein 970:1011 the entire 1591-amino acid S-layer protein 970:1011 Mass spectrometry (MS) analysis showed an O-glycan attached to 13 sites distributed over the entire 1591-amino acid S-layer protein. 27847504 6 68 theme HexNAc 1108:1113 arg1 residues 1060:1067 six monosaccharide residues 1041:1067 six monosaccharide residues 1041:1067 This glycan is composed of six monosaccharide residues, of which five are N-acetylhexosamine (HexNAc) residues. 27847504 6 68 theme HexNAc 1108:1113 arg1 five 1079:1082 five 1079:1082 five 1079:1082 This glycan is composed of six monosaccharide residues, of which five are N-acetylhexosamine (HexNAc) residues. 27847504 6 68 theme HexNAc 1108:1113 arg1 residues 1116:1123 N-acetylhexosamine (HexNAc) residues 1088:1123 N-acetylhexosamine (HexNAc) residues 1088:1123 This glycan is composed of six monosaccharide residues, of which five are N-acetylhexosamine (HexNAc) residues. 27847504 2 69 theme interaction 465:475 arg1 zone 477:480 the direct interaction zone 454:480 the direct interaction zone of anammox bacteria with the environment 454:521 The cell of anammox bacteria comprises three membrane-bound compartments and is surrounded by a two-dimensional crystalline S-layer representing the direct interaction zone of anammox bacteria with the environment. 27847504 4 70 theme glycosylation 775:787 arg1 characterization 735:750 the characterization 731:750 the characterization of the S-layer protein glycosylation 731:787 In the present study, we focussed on the characterization of the S-layer protein glycosylation in order to increase our knowledge on the cell surface characteristics of anammox bacteria. 27847504 5 71 theme acid 992:995 arg1 protein 1005:1011 the entire 1591-amino acid S-layer protein 970:1011 the entire 1591-amino acid S-layer protein 970:1011 Mass spectrometry (MS) analysis showed an O-glycan attached to 13 sites distributed over the entire 1591-amino acid S-layer protein. 27847504 6 72 theme N-acetylhexosamine 1088:1105 arg1 residues 1060:1067 six monosaccharide residues 1041:1067 six monosaccharide residues 1041:1067 This glycan is composed of six monosaccharide residues, of which five are N-acetylhexosamine (HexNAc) residues. 27847504 6 72 theme N-acetylhexosamine 1088:1105 arg1 five 1079:1082 five 1079:1082 five 1079:1082 This glycan is composed of six monosaccharide residues, of which five are N-acetylhexosamine (HexNAc) residues. 27847504 6 72 theme N-acetylhexosamine 1088:1105 arg1 residues 1116:1123 N-acetylhexosamine (HexNAc) residues 1088:1123 N-acetylhexosamine (HexNAc) residues 1088:1123 This glycan is composed of six monosaccharide residues, of which five are N-acetylhexosamine (HexNAc) residues. 27847504 10 73 theme S-layer 1509:1515 arg1 Kustd1514 1525:1533 the S-layer protein Kustd1514 1505:1533 the S-layer protein Kustd1514 of K. stuttgartiensis 1505:1555 This study presents the first characterization of a glycoprotein in a planctomycete and shows that the S-layer protein Kustd1514 of K. stuttgartiensis is heavily glycosylated with an O-linked oligosaccharide which is additionally modified by methylation. 27847504 11 74 theme surface 1757:1763 arg1 diversification 1710:1724 the diversification 1706:1724 the diversification of the K. stuttgartiensis cell surface 1706:1763 S-layer glycosylation clearly contributes to the diversification of the K. stuttgartiensis cell surface and can be expected to influence the interaction of the bacterium with other cells or abiotic surfaces. 27847504 0 75 theme Anammox 27:33 arg1 stuttgartiensis 54:68 the Anammox Bacterium Kuenenia stuttgartiensis 23:68 the Anammox Bacterium Kuenenia stuttgartiensis 23:68 The S-Layer Protein of the Anammox Bacterium Kuenenia stuttgartiensis Is Heavily O-Glycosylated. 27847504 1 76 theme specialized 286:296 arg1 organelle 298:306 a specialized organelle 284:306 a specialized organelle 284:306 Anaerobic ammonium oxidation (anammox) bacteria are a distinct group of Planctomycetes that are characterized by their unique ability to perform anammox with nitrite to dinitrogen gas in a specialized organelle. 27847504 2 77 theme bacteria 493:500 arg1 zone 477:480 the direct interaction zone 454:480 the direct interaction zone of anammox bacteria with the environment 454:521 The cell of anammox bacteria comprises three membrane-bound compartments and is surrounded by a two-dimensional crystalline S-layer representing the direct interaction zone of anammox bacteria with the environment. 27847504 11 78 theme stuttgartiensis 1736:1750 arg1 surface 1757:1763 the K. stuttgartiensis cell surface 1729:1763 the K. stuttgartiensis cell surface 1729:1763 S-layer glycosylation clearly contributes to the diversification of the K. stuttgartiensis cell surface and can be expected to influence the interaction of the bacterium with other cells or abiotic surfaces. 27847504 2 79 theme two-dimensional 405:419 arg1 S-layer 433:439 a two-dimensional crystalline S-layer 403:439 a two-dimensional crystalline S-layer representing the direct interaction zone of anammox bacteria with the environment 403:521 The cell of anammox bacteria comprises three membrane-bound compartments and is surrounded by a two-dimensional crystalline S-layer representing the direct interaction zone of anammox bacteria with the environment. 27847504 0 80 theme Kuenenia 45:52 arg1 stuttgartiensis 54:68 the Anammox Bacterium Kuenenia stuttgartiensis 23:68 the Anammox Bacterium Kuenenia stuttgartiensis 23:68 The S-Layer Protein of the Anammox Bacterium Kuenenia stuttgartiensis Is Heavily O-Glycosylated. 27847504 9 81 theme methylation 1379:1389 arg1 degree 1369:1374 an extensive degree 1356:1374 an extensive degree of methylation of the glycan 1356:1403 Two of the HexNAc residues were also found to contain a methyl group, thereby leading to an extensive degree of methylation of the glycan. 27847504 10 82 theme K. 1538:1539 arg1 stuttgartiensis 1541:1555 K. stuttgartiensis 1538:1555 K. stuttgartiensis 1538:1555 This study presents the first characterization of a glycoprotein in a planctomycete and shows that the S-layer protein Kustd1514 of K. stuttgartiensis is heavily glycosylated with an O-linked oligosaccharide which is additionally modified by methylation. 27847504 4 83 theme bacteria 871:878 arg1 characteristics 844:858 the cell surface characteristics 827:858 the cell surface characteristics of anammox bacteria 827:878 In the present study, we focussed on the characterization of the S-layer protein glycosylation in order to increase our knowledge on the cell surface characteristics of anammox bacteria. 27847504 2 84 theme bacteria 329:336 arg1 cell 313:316 The cell 309:316 The cell of anammox bacteria 309:336 The cell of anammox bacteria comprises three membrane-bound compartments and is surrounded by a two-dimensional crystalline S-layer representing the direct interaction zone of anammox bacteria with the environment. 27847504 8 85 from monosaccharide 1198:1211 arg1 glycan 1220:1225 the glycan 1216:1225 the glycan 1216:1225 The sixth monosaccharide in the glycan is a putative dimethylated deoxyhexose. 27847504 10 86 link O-linked 1589:1596 arg1 oligosaccharide 1598:1612 an O-linked oligosaccharide 1586:1612 an O-linked oligosaccharide which is additionally modified by methylation 1586:1658 This study presents the first characterization of a glycoprotein in a planctomycete and shows that the S-layer protein Kustd1514 of K. stuttgartiensis is heavily glycosylated with an O-linked oligosaccharide which is additionally modified by methylation. 27847504 1 87 with anammox 242:248 arg1 nitrite 255:261 nitrite 255:261 nitrite 255:261 Anaerobic ammonium oxidation (anammox) bacteria are a distinct group of Planctomycetes that are characterized by their unique ability to perform anammox with nitrite to dinitrogen gas in a specialized organelle. 27847504 4 88 theme surface 836:842 arg1 characteristics 844:858 the cell surface characteristics 827:858 the cell surface characteristics of anammox bacteria 827:878 In the present study, we focussed on the characterization of the S-layer protein glycosylation in order to increase our knowledge on the cell surface characteristics of anammox bacteria. 27847504 11 89 gly glycosylation 1669:1681 arg1 surface 1757:1763 the K. stuttgartiensis cell surface 1729:1763 the K. stuttgartiensis cell surface 1729:1763 S-layer glycosylation clearly contributes to the diversification of the K. stuttgartiensis cell surface and can be expected to influence the interaction of the bacterium with other cells or abiotic surfaces. 27595232 2 0 gly glycosylation 201:213 arg2 types 241:245 essentially all types 225:245 essentially all types of cancers 225:256 Aberrant glycosylation occurs in essentially all types of cancers and results in increased sialylation. 27595232 4 1 theme Siglec-9 504:511 arg1 engagement 490:499 engagement 490:499 engagement of Siglec-9 490:511 Here we found that this cancer-specific MUC1 glycoform, through engagement of Siglec-9, 'educated' myeloid cells to release factors associated with determination of the tumor microenvironment and disease progression. 27595232 6 2 theme MUC1-ST 813:819 arg1 Binding 802:808 Binding 802:808 Binding of MUC1-ST to Siglec-9 802:831 Binding of MUC1-ST to Siglec-9 did not activate the phosphatases SHP-1 or SHP-2 but, unexpectedly, induced calcium flux that led to activation of the kinases MEK-ERK. 27595232 1 3 theme myeloid 177:183 arg1 cells 185:189 myeloid cells 177:189 myeloid cells 177:189 Siglec-9 is a sialic-acid-binding lectin expressed predominantly on myeloid cells. 27595232 0 4 theme Siglec-9 99:106 arg1 engagement 74:83 engagement 74:83 engagement of the lectin Siglec-9 74:106 The mucin MUC1 modulates the tumor immunological microenvironment through engagement of the lectin Siglec-9. 27595232 3 5 dep short 380:384 arg1 sialylated 387:396 sialylated 387:396 sialylated 387:396 Thus, when the mucin MUC1 is expressed on cancer cells, it is decorated by multiple short, sialylated O-linked glycans (MUC1-ST). 27595232 0 6 theme lectin 92:97 arg1 Siglec-9 99:106 the lectin Siglec-9 88:106 the lectin Siglec-9 88:106 The mucin MUC1 modulates the tumor immunological microenvironment through engagement of the lectin Siglec-9. 27595232 4 7 theme MUC1 466:469 arg1 glycoform 471:479 this cancer-specific MUC1 glycoform 445:479 this cancer-specific MUC1 glycoform 445:479 Here we found that this cancer-specific MUC1 glycoform, through engagement of Siglec-9, 'educated' myeloid cells to release factors associated with determination of the tumor microenvironment and disease progression. 27595232 7 8 theme Siglec-9 1100:1107 arg1 engagement 1086:1095 engagement 1086:1095 engagement of Siglec-9 1086:1107 This work defines a critical role for aberrantly glycosylated MUC1 and identifies an activating pathway that follows engagement of Siglec-9. 27595232 6 9 theme MEK-ERK 960:966 arg1 activation 934:943 activation 934:943 activation of the kinases MEK-ERK 934:966 Binding of MUC1-ST to Siglec-9 did not activate the phosphatases SHP-1 or SHP-2 but, unexpectedly, induced calcium flux that led to activation of the kinases MEK-ERK. 27595232 4 10 theme cancer-specific 450:464 arg1 glycoform 471:479 this cancer-specific MUC1 glycoform 445:479 this cancer-specific MUC1 glycoform 445:479 Here we found that this cancer-specific MUC1 glycoform, through engagement of Siglec-9, 'educated' myeloid cells to release factors associated with determination of the tumor microenvironment and disease progression. 27595232 0 11 theme immunological 35:47 arg1 microenvironment 49:64 the tumor immunological microenvironment 25:64 the tumor immunological microenvironment 25:64 The mucin MUC1 modulates the tumor immunological microenvironment through engagement of the lectin Siglec-9. 27595232 0 12 theme mucin 4:8 arg1 MUC1 10:13 The mucin MUC1 0:13 The mucin MUC1 0:13 The mucin MUC1 modulates the tumor immunological microenvironment through engagement of the lectin Siglec-9. 27595232 6 13 theme kinases 952:958 arg1 MEK-ERK 960:966 the kinases MEK-ERK 948:966 the kinases MEK-ERK 948:966 Binding of MUC1-ST to Siglec-9 did not activate the phosphatases SHP-1 or SHP-2 but, unexpectedly, induced calcium flux that led to activation of the kinases MEK-ERK. 27595232 4 14 theme myeloid 525:531 arg1 cells 533:537 'educated' myeloid cells 514:537 'educated' myeloid cells 514:537 Here we found that this cancer-specific MUC1 glycoform, through engagement of Siglec-9, 'educated' myeloid cells to release factors associated with determination of the tumor microenvironment and disease progression. 27595232 4 15 theme disease 622:628 arg1 progression 630:640 disease progression 622:640 disease progression 622:640 Here we found that this cancer-specific MUC1 glycoform, through engagement of Siglec-9, 'educated' myeloid cells to release factors associated with determination of the tumor microenvironment and disease progression. 27595232 3 16 theme multiple 371:378 arg1 MUC1-ST 416:422 MUC1-ST 416:422 MUC1-ST 416:422 Thus, when the mucin MUC1 is expressed on cancer cells, it is decorated by multiple short, sialylated O-linked glycans (MUC1-ST). 27595232 3 16 theme multiple 371:378 arg1 glycans 407:413 multiple short, sialylated O-linked glycans 371:413 multiple short, sialylated O-linked glycans (MUC1-ST) 371:423 Thus, when the mucin MUC1 is expressed on cancer cells, it is decorated by multiple short, sialylated O-linked glycans (MUC1-ST). 27595232 7 17 theme activating 1054:1063 arg1 pathway 1065:1071 an activating pathway 1051:1071 an activating pathway that follows engagement of Siglec-9 1051:1107 This work defines a critical role for aberrantly glycosylated MUC1 and identifies an activating pathway that follows engagement of Siglec-9. 27595232 4 18 gly glycoform 471:479 arg1 MUC1 466:469 this cancer-specific MUC1 glycoform 445:479 this cancer-specific MUC1 glycoform 445:479 Here we found that this cancer-specific MUC1 glycoform, through engagement of Siglec-9, 'educated' myeloid cells to release factors associated with determination of the tumor microenvironment and disease progression. 27595232 0 19 theme tumor 29:33 arg1 microenvironment 49:64 the tumor immunological microenvironment 25:64 the tumor immunological microenvironment 25:64 The mucin MUC1 modulates the tumor immunological microenvironment through engagement of the lectin Siglec-9. 27595232 2 20 theme Aberrant 192:199 arg1 glycosylation 201:213 Aberrant glycosylation 192:213 Aberrant glycosylation 192:213 Aberrant glycosylation occurs in essentially all types of cancers and results in increased sialylation. 27595232 5 21 theme checkpoint 777:786 arg1 PD-L1 795:799 the checkpoint ligand PD-L1 773:799 the checkpoint ligand PD-L1 773:799 Moreover, MUC1-ST induced macrophages to display a tumor-associated macrophage (TAM)-like phenotype, with increased expression of the checkpoint ligand PD-L1. 27595232 5 22 theme -like 727:731 arg1 phenotype 733:741 a tumor-associated macrophage (TAM)-like phenotype 692:741 a tumor-associated macrophage (TAM)-like phenotype 692:741 Moreover, MUC1-ST induced macrophages to display a tumor-associated macrophage (TAM)-like phenotype, with increased expression of the checkpoint ligand PD-L1. 27595232 3 23 link O-linked 398:405 arg1 MUC1-ST 416:422 MUC1-ST 416:422 MUC1-ST 416:422 Thus, when the mucin MUC1 is expressed on cancer cells, it is decorated by multiple short, sialylated O-linked glycans (MUC1-ST). 27595232 3 23 link O-linked 398:405 arg1 glycans 407:413 multiple short, sialylated O-linked glycans 371:413 multiple short, sialylated O-linked glycans (MUC1-ST) 371:423 Thus, when the mucin MUC1 is expressed on cancer cells, it is decorated by multiple short, sialylated O-linked glycans (MUC1-ST). 27595232 7 24 theme critical 989:996 arg1 role 998:1001 a critical role 987:1001 a critical role for aberrantly glycosylated MUC1 987:1034 This work defines a critical role for aberrantly glycosylated MUC1 and identifies an activating pathway that follows engagement of Siglec-9. 27595232 6 25 dep phosphatases 854:865 arg1 phosphatases 854:865 the phosphatases SHP-1 or SHP-2 850:880 the phosphatases SHP-1 or SHP-2 850:880 Binding of MUC1-ST to Siglec-9 did not activate the phosphatases SHP-1 or SHP-2 but, unexpectedly, induced calcium flux that led to activation of the kinases MEK-ERK. 27595232 6 25 dep phosphatases 854:865 arg1 SHP-2 876:880 SHP-2 876:880 SHP-2 876:880 Binding of MUC1-ST to Siglec-9 did not activate the phosphatases SHP-1 or SHP-2 but, unexpectedly, induced calcium flux that led to activation of the kinases MEK-ERK. 27595232 6 25 dep phosphatases 854:865 arg1 SHP-1 867:871 SHP-1 867:871 SHP-1 867:871 Binding of MUC1-ST to Siglec-9 did not activate the phosphatases SHP-1 or SHP-2 but, unexpectedly, induced calcium flux that led to activation of the kinases MEK-ERK. 27595232 5 26 theme ligand 788:793 arg1 PD-L1 795:799 the checkpoint ligand PD-L1 773:799 the checkpoint ligand PD-L1 773:799 Moreover, MUC1-ST induced macrophages to display a tumor-associated macrophage (TAM)-like phenotype, with increased expression of the checkpoint ligand PD-L1. 27595232 6 27 dep activate 841:848 arg1 induced 901:907 induced 901:907 induced calcium flux that led to activation of the kinases MEK-ERK 901:966 Binding of MUC1-ST to Siglec-9 did not activate the phosphatases SHP-1 or SHP-2 but, unexpectedly, induced calcium flux that led to activation of the kinases MEK-ERK. 27595232 5 28 theme PD-L1 795:799 arg1 expression 759:768 increased expression 749:768 increased expression of the checkpoint ligand PD-L1 749:799 Moreover, MUC1-ST induced macrophages to display a tumor-associated macrophage (TAM)-like phenotype, with increased expression of the checkpoint ligand PD-L1. 27595232 3 29 theme O-linked 398:405 arg1 MUC1-ST 416:422 MUC1-ST 416:422 MUC1-ST 416:422 Thus, when the mucin MUC1 is expressed on cancer cells, it is decorated by multiple short, sialylated O-linked glycans (MUC1-ST). 27595232 3 29 theme O-linked 398:405 arg1 glycans 407:413 multiple short, sialylated O-linked glycans 371:413 multiple short, sialylated O-linked glycans (MUC1-ST) 371:423 Thus, when the mucin MUC1 is expressed on cancer cells, it is decorated by multiple short, sialylated O-linked glycans (MUC1-ST). 27595232 7 30 gly glycosylated 1018:1029 arg1 MUC1 1031:1034 aberrantly glycosylated MUC1 1007:1034 aberrantly glycosylated MUC1 1007:1034 This work defines a critical role for aberrantly glycosylated MUC1 and identifies an activating pathway that follows engagement of Siglec-9. 27595232 4 31 theme educated 515:522 arg1 cells 533:537 'educated' myeloid cells 514:537 'educated' myeloid cells 514:537 Here we found that this cancer-specific MUC1 glycoform, through engagement of Siglec-9, 'educated' myeloid cells to release factors associated with determination of the tumor microenvironment and disease progression. 27595232 2 32 theme cancers 250:256 arg1 types 241:245 essentially all types 225:245 essentially all types of cancers 225:256 Aberrant glycosylation occurs in essentially all types of cancers and results in increased sialylation. 27595232 1 33 theme sialic-acid-binding 123:141 arg1 lectin 143:148 a sialic-acid-binding lectin 121:148 a sialic-acid-binding lectin expressed predominantly on myeloid cells 121:189 Siglec-9 is a sialic-acid-binding lectin expressed predominantly on myeloid cells. 27595232 1 33 theme sialic-acid-binding 123:141 arg1 Siglec-9 109:116 Siglec-9 109:116 Siglec-9 109:116 Siglec-9 is a sialic-acid-binding lectin expressed predominantly on myeloid cells. 27595232 3 34 theme mucin 311:315 arg1 MUC1 317:320 the mucin MUC1 307:320 the mucin MUC1 307:320 Thus, when the mucin MUC1 is expressed on cancer cells, it is decorated by multiple short, sialylated O-linked glycans (MUC1-ST). 27595232 2 35 theme increased 273:281 arg1 sialylation 283:293 increased sialylation 273:293 increased sialylation 273:293 Aberrant glycosylation occurs in essentially all types of cancers and results in increased sialylation. 27595232 3 36 theme cancer 338:343 arg1 cells 345:349 cancer cells 338:349 cancer cells 338:349 Thus, when the mucin MUC1 is expressed on cancer cells, it is decorated by multiple short, sialylated O-linked glycans (MUC1-ST). 27595232 7 37 theme glycosylated 1018:1029 arg1 MUC1 1031:1034 aberrantly glycosylated MUC1 1007:1034 aberrantly glycosylated MUC1 1007:1034 This work defines a critical role for aberrantly glycosylated MUC1 and identifies an activating pathway that follows engagement of Siglec-9. 27595232 4 38 theme microenvironment 601:616 arg1 progression 630:640 disease progression 622:640 disease progression 622:640 Here we found that this cancer-specific MUC1 glycoform, through engagement of Siglec-9, 'educated' myeloid cells to release factors associated with determination of the tumor microenvironment and disease progression. 27595232 4 38 theme microenvironment 601:616 arg1 determination 574:586 determination 574:586 determination of the tumor microenvironment 574:616 Here we found that this cancer-specific MUC1 glycoform, through engagement of Siglec-9, 'educated' myeloid cells to release factors associated with determination of the tumor microenvironment and disease progression. 27595232 5 39 theme increased 749:757 arg1 expression 759:768 increased expression 749:768 increased expression of the checkpoint ligand PD-L1 749:799 Moreover, MUC1-ST induced macrophages to display a tumor-associated macrophage (TAM)-like phenotype, with increased expression of the checkpoint ligand PD-L1. 27595232 6 40 theme calcium 909:915 arg1 flux 917:920 calcium flux 909:920 calcium flux that led to activation of the kinases MEK-ERK 909:966 Binding of MUC1-ST to Siglec-9 did not activate the phosphatases SHP-1 or SHP-2 but, unexpectedly, induced calcium flux that led to activation of the kinases MEK-ERK. 27595232 3 41 theme short 380:384 arg1 MUC1-ST 416:422 MUC1-ST 416:422 MUC1-ST 416:422 Thus, when the mucin MUC1 is expressed on cancer cells, it is decorated by multiple short, sialylated O-linked glycans (MUC1-ST). 27595232 3 41 theme short 380:384 arg1 glycans 407:413 multiple short, sialylated O-linked glycans 371:413 multiple short, sialylated O-linked glycans (MUC1-ST) 371:423 Thus, when the mucin MUC1 is expressed on cancer cells, it is decorated by multiple short, sialylated O-linked glycans (MUC1-ST). 27595232 4 42 theme tumor 595:599 arg1 microenvironment 601:616 the tumor microenvironment 591:616 the tumor microenvironment 591:616 Here we found that this cancer-specific MUC1 glycoform, through engagement of Siglec-9, 'educated' myeloid cells to release factors associated with determination of the tumor microenvironment and disease progression. 27622469 0 0 theme Proteins 102:109 arg1 Visualization 39:51 Specific Visualization 30:51 Specific Visualization 30:51 An OGA-Resistant Probe Allows Specific Visualization and Accurate Identification of O-GlcNAc-Modified Proteins in Cells. 27622469 0 0 theme Proteins 102:109 arg1 Identification 66:79 Accurate Identification 57:79 Accurate Identification 57:79 An OGA-Resistant Probe Allows Specific Visualization and Accurate Identification of O-GlcNAc-Modified Proteins in Cells. 27622469 6 1 theme group 989:993 arg1 absence 967:973 the absence 963:973 the absence of a hydroxyl group at C4 963:999 Due to the absence of a hydroxyl group at C4, this probe is less incorporated into α/β 4-GlcNAc or GalNAc containing glycoconjugates. 27622469 9 2 from tool 1485:1488 arg1 tracking 1493:1500 tracking 1493:1500 tracking 1493:1500 This probe represents a more potent and selective tool in tracking, capturing, and identifying O-GlcNAc-modified proteins in cells and cell lysates. 27622469 1 3 theme essential 170:178 arg1 modification 214:225 an essential and ubiquitous post-translational modification 167:225 an essential and ubiquitous post-translational modification present in nucleic and cytoplasmic proteins of multicellular eukaryotes 167:297 O-linked β-N-acetyl-glucosamine (O-GlcNAc) is an essential and ubiquitous post-translational modification present in nucleic and cytoplasmic proteins of multicellular eukaryotes. 27622469 1 3 theme essential 170:178 arg1 β-N-acetyl-glucosamine 130:151 O-linked β-N-acetyl-glucosamine 121:151 O-linked β-N-acetyl-glucosamine (O-GlcNAc) 121:162 O-linked β-N-acetyl-glucosamine (O-GlcNAc) is an essential and ubiquitous post-translational modification present in nucleic and cytoplasmic proteins of multicellular eukaryotes. 27622469 7 4 theme O-4dGlcNAz 1107:1116 arg1 resistant 1135:1143 resistant 1135:1143 resistant 1135:1143 Furthermore, the O-4dGlcNAz modification was resistant to the hydrolysis of O-GlcNAcase (OGA), which greatly enhanced the efficiency of incorporation for O-GlcNAcylation. 27622469 7 4 theme O-4dGlcNAz 1107:1116 arg1 modification 1118:1129 the O-4dGlcNAz modification 1103:1129 the O-4dGlcNAz modification 1103:1129 Furthermore, the O-4dGlcNAz modification was resistant to the hydrolysis of O-GlcNAcase (OGA), which greatly enhanced the efficiency of incorporation for O-GlcNAcylation. 27622469 0 5 theme O-GlcNAc-Modified 84:100 arg1 Proteins 102:109 O-GlcNAc-Modified Proteins 84:109 O-GlcNAc-Modified Proteins 84:109 An OGA-Resistant Probe Allows Specific Visualization and Accurate Identification of O-GlcNAc-Modified Proteins in Cells. 27622469 6 6 theme hydroxyl 980:987 arg1 group 989:993 a hydroxyl group 978:993 a hydroxyl group at C4 978:999 Due to the absence of a hydroxyl group at C4, this probe is less incorporated into α/β 4-GlcNAc or GalNAc containing glycoconjugates. 27622469 3 7 theme multiple 564:571 arg1 pathways 587:594 multiple glycosylation pathways 564:594 multiple glycosylation pathways 564:594 However, these chemical probes either enter multiple glycosylation pathways or have low labeling efficiency. 27622469 4 8 theme selective 640:648 arg1 probes 661:666 selective and potent probes 640:666 selective and potent probes 640:666 Therefore, selective and potent probes are needed to assess this modification. 27622469 8 9 from identification 1375:1388 arg1 cells 1356:1360 cells 1356:1360 cells 1356:1360 Combined with a click reaction, Ac34dGlcNAz allowed the selective visualization of O-GlcNAc in cells and accurate identification of O-GlcNAc-modified proteins with LC-MS/MS. 27622469 2 10 theme GlcNAc 338:343 arg1 analogues 355:363 GlcNAc or GalNAc analogues 338:363 GlcNAc or GalNAc analogues bearing ketone or azide 338:387 The metabolic chemical probes such as GlcNAc or GalNAc analogues bearing ketone or azide handles, in conjunction with bioorthogonal reactions, provide a powerful approach for detecting and identifying this modification. 27622469 3 11 theme labeling 608:615 arg1 efficiency 617:626 low labeling efficiency 604:626 low labeling efficiency 604:626 However, these chemical probes either enter multiple glycosylation pathways or have low labeling efficiency. 27622469 4 12 theme potent 654:659 arg1 probes 661:666 selective and potent probes 640:666 selective and potent probes 640:666 Therefore, selective and potent probes are needed to assess this modification. 27622469 7 13 theme O-GlcNAcase 1166:1176 arg1 hydrolysis 1152:1161 the hydrolysis 1148:1161 the hydrolysis of O-GlcNAcase (OGA), which greatly enhanced the efficiency of incorporation for O-GlcNAcylation 1148:1258 Furthermore, the O-4dGlcNAz modification was resistant to the hydrolysis of O-GlcNAcase (OGA), which greatly enhanced the efficiency of incorporation for O-GlcNAcylation. 27622469 1 14 theme ubiquitous 184:193 arg1 modification 214:225 an essential and ubiquitous post-translational modification 167:225 an essential and ubiquitous post-translational modification present in nucleic and cytoplasmic proteins of multicellular eukaryotes 167:297 O-linked β-N-acetyl-glucosamine (O-GlcNAc) is an essential and ubiquitous post-translational modification present in nucleic and cytoplasmic proteins of multicellular eukaryotes. 27622469 1 14 theme ubiquitous 184:193 arg1 β-N-acetyl-glucosamine 130:151 O-linked β-N-acetyl-glucosamine 121:151 O-linked β-N-acetyl-glucosamine (O-GlcNAc) 121:162 O-linked β-N-acetyl-glucosamine (O-GlcNAc) is an essential and ubiquitous post-translational modification present in nucleic and cytoplasmic proteins of multicellular eukaryotes. 27622469 6 15 theme α/β 1039:1041 arg1 4-GlcNAc 1043:1050 α/β 4-GlcNAc 1039:1050 α/β 4-GlcNAc 1039:1050 Due to the absence of a hydroxyl group at C4, this probe is less incorporated into α/β 4-GlcNAc or GalNAc containing glycoconjugates. 27622469 0 16 from Visualization 39:51 arg1 Cells 114:118 Cells 114:118 Cells 114:118 An OGA-Resistant Probe Allows Specific Visualization and Accurate Identification of O-GlcNAc-Modified Proteins in Cells. 27622469 6 17 from absence 967:973 arg1 C4 998:999 C4 998:999 C4 998:999 Due to the absence of a hydroxyl group at C4, this probe is less incorporated into α/β 4-GlcNAc or GalNAc containing glycoconjugates. 27622469 1 18 theme post-translational 195:212 arg1 modification 214:225 an essential and ubiquitous post-translational modification 167:225 an essential and ubiquitous post-translational modification present in nucleic and cytoplasmic proteins of multicellular eukaryotes 167:297 O-linked β-N-acetyl-glucosamine (O-GlcNAc) is an essential and ubiquitous post-translational modification present in nucleic and cytoplasmic proteins of multicellular eukaryotes. 27622469 1 18 theme post-translational 195:212 arg1 β-N-acetyl-glucosamine 130:151 O-linked β-N-acetyl-glucosamine 121:151 O-linked β-N-acetyl-glucosamine (O-GlcNAc) 121:162 O-linked β-N-acetyl-glucosamine (O-GlcNAc) is an essential and ubiquitous post-translational modification present in nucleic and cytoplasmic proteins of multicellular eukaryotes. 27622469 0 19 theme OGA-Resistant 3:15 arg1 Probe 17:21 An OGA-Resistant Probe 0:21 An OGA-Resistant Probe 0:21 An OGA-Resistant Probe Allows Specific Visualization and Accurate Identification of O-GlcNAc-Modified Proteins in Cells. 27622469 8 20 theme selective 1317:1325 arg1 visualization 1327:1339 the selective visualization 1313:1339 the selective visualization of O-GlcNAc in cells 1313:1360 Combined with a click reaction, Ac34dGlcNAz allowed the selective visualization of O-GlcNAc in cells and accurate identification of O-GlcNAc-modified proteins with LC-MS/MS. 27622469 5 21 theme O-GlcNAc 937:944 arg1 proteins 946:953 O-GlcNAc proteins 937:953 O-GlcNAc proteins 937:953 We report here the development of a novel probe, 1,3,6-tri-O-acetyl-2-azidoacetamido-2,4-dideoxy-d-glucopyranose (Ac34dGlcNAz), that can be processed by the GalNAc salvage pathway and transferred by O-GlcNAc transferase (OGT) to O-GlcNAc proteins. 27622469 1 22 theme present 227:233 arg1 modification 214:225 an essential and ubiquitous post-translational modification 167:225 an essential and ubiquitous post-translational modification present in nucleic and cytoplasmic proteins of multicellular eukaryotes 167:297 O-linked β-N-acetyl-glucosamine (O-GlcNAc) is an essential and ubiquitous post-translational modification present in nucleic and cytoplasmic proteins of multicellular eukaryotes. 27622469 1 22 theme present 227:233 arg1 β-N-acetyl-glucosamine 130:151 O-linked β-N-acetyl-glucosamine 121:151 O-linked β-N-acetyl-glucosamine (O-GlcNAc) 121:162 O-linked β-N-acetyl-glucosamine (O-GlcNAc) is an essential and ubiquitous post-translational modification present in nucleic and cytoplasmic proteins of multicellular eukaryotes. 27622469 5 23 theme O-GlcNAc 907:914 arg1 OGT 929:931 OGT 929:931 OGT 929:931 We report here the development of a novel probe, 1,3,6-tri-O-acetyl-2-azidoacetamido-2,4-dideoxy-d-glucopyranose (Ac34dGlcNAz), that can be processed by the GalNAc salvage pathway and transferred by O-GlcNAc transferase (OGT) to O-GlcNAc proteins. 27622469 5 23 theme O-GlcNAc 907:914 arg1 transferase 916:926 O-GlcNAc transferase 907:926 O-GlcNAc transferase (OGT) to O-GlcNAc proteins 907:953 We report here the development of a novel probe, 1,3,6-tri-O-acetyl-2-azidoacetamido-2,4-dideoxy-d-glucopyranose (Ac34dGlcNAz), that can be processed by the GalNAc salvage pathway and transferred by O-GlcNAc transferase (OGT) to O-GlcNAc proteins. 27622469 2 24 theme GalNAc 348:353 arg1 analogues 355:363 GlcNAc or GalNAc analogues 338:363 GlcNAc or GalNAc analogues bearing ketone or azide 338:387 The metabolic chemical probes such as GlcNAc or GalNAc analogues bearing ketone or azide handles, in conjunction with bioorthogonal reactions, provide a powerful approach for detecting and identifying this modification. 27622469 8 25 theme O-GlcNAc 1344:1351 arg1 identification 1375:1388 accurate identification 1366:1388 accurate identification of O-GlcNAc-modified proteins with LC-MS/MS 1366:1432 Combined with a click reaction, Ac34dGlcNAz allowed the selective visualization of O-GlcNAc in cells and accurate identification of O-GlcNAc-modified proteins with LC-MS/MS. 27622469 8 25 theme O-GlcNAc 1344:1351 arg1 visualization 1327:1339 the selective visualization 1313:1339 the selective visualization of O-GlcNAc in cells 1313:1360 Combined with a click reaction, Ac34dGlcNAz allowed the selective visualization of O-GlcNAc in cells and accurate identification of O-GlcNAc-modified proteins with LC-MS/MS. 27622469 7 26 theme incorporation 1226:1238 arg1 efficiency 1212:1221 the efficiency 1208:1221 the efficiency of incorporation for O-GlcNAcylation 1208:1258 Furthermore, the O-4dGlcNAz modification was resistant to the hydrolysis of O-GlcNAcase (OGA), which greatly enhanced the efficiency of incorporation for O-GlcNAcylation. 27622469 1 27 theme O-linked 121:128 arg1 O-GlcNAc 154:161 O-GlcNAc 154:161 O-GlcNAc 154:161 O-linked β-N-acetyl-glucosamine (O-GlcNAc) is an essential and ubiquitous post-translational modification present in nucleic and cytoplasmic proteins of multicellular eukaryotes. 27622469 1 27 theme O-linked 121:128 arg1 modification 214:225 an essential and ubiquitous post-translational modification 167:225 an essential and ubiquitous post-translational modification present in nucleic and cytoplasmic proteins of multicellular eukaryotes 167:297 O-linked β-N-acetyl-glucosamine (O-GlcNAc) is an essential and ubiquitous post-translational modification present in nucleic and cytoplasmic proteins of multicellular eukaryotes. 27622469 1 27 theme O-linked 121:128 arg1 β-N-acetyl-glucosamine 130:151 O-linked β-N-acetyl-glucosamine 121:151 O-linked β-N-acetyl-glucosamine (O-GlcNAc) 121:162 O-linked β-N-acetyl-glucosamine (O-GlcNAc) is an essential and ubiquitous post-translational modification present in nucleic and cytoplasmic proteins of multicellular eukaryotes. 27622469 1 28 theme nucleic 238:244 arg1 proteins 262:269 nucleic and cytoplasmic proteins 238:269 nucleic and cytoplasmic proteins of multicellular eukaryotes 238:297 O-linked β-N-acetyl-glucosamine (O-GlcNAc) is an essential and ubiquitous post-translational modification present in nucleic and cytoplasmic proteins of multicellular eukaryotes. 27622469 5 29 theme GalNAc 865:870 arg1 pathway 880:886 the GalNAc salvage pathway 861:886 the GalNAc salvage pathway 861:886 We report here the development of a novel probe, 1,3,6-tri-O-acetyl-2-azidoacetamido-2,4-dideoxy-d-glucopyranose (Ac34dGlcNAz), that can be processed by the GalNAc salvage pathway and transferred by O-GlcNAc transferase (OGT) to O-GlcNAc proteins. 27622469 9 30 dep represents 1446:1455 arg1 capturing 1503:1511 capturing 1503:1511 capturing 1503:1511 This probe represents a more potent and selective tool in tracking, capturing, and identifying O-GlcNAc-modified proteins in cells and cell lysates. 27622469 9 30 dep represents 1446:1455 arg1 identifying 1518:1528 identifying 1518:1528 identifying O-GlcNAc-modified proteins in cells and cell lysates 1518:1581 This probe represents a more potent and selective tool in tracking, capturing, and identifying O-GlcNAc-modified proteins in cells and cell lysates. 27622469 9 31 theme cell 1570:1573 arg1 lysates 1575:1581 cell lysates 1570:1581 cell lysates 1570:1581 This probe represents a more potent and selective tool in tracking, capturing, and identifying O-GlcNAc-modified proteins in cells and cell lysates. 27622469 8 32 theme proteins 1411:1418 arg1 identification 1375:1388 accurate identification 1366:1388 accurate identification of O-GlcNAc-modified proteins with LC-MS/MS 1366:1432 Combined with a click reaction, Ac34dGlcNAz allowed the selective visualization of O-GlcNAc in cells and accurate identification of O-GlcNAc-modified proteins with LC-MS/MS. 27622469 8 32 theme proteins 1411:1418 arg1 visualization 1327:1339 the selective visualization 1313:1339 the selective visualization of O-GlcNAc in cells 1313:1360 Combined with a click reaction, Ac34dGlcNAz allowed the selective visualization of O-GlcNAc in cells and accurate identification of O-GlcNAc-modified proteins with LC-MS/MS. 27622469 2 33 theme bioorthogonal 418:430 arg1 reactions 432:440 bioorthogonal reactions 418:440 bioorthogonal reactions 418:440 The metabolic chemical probes such as GlcNAc or GalNAc analogues bearing ketone or azide handles, in conjunction with bioorthogonal reactions, provide a powerful approach for detecting and identifying this modification. 27622469 2 34 theme powerful 453:460 arg1 approach 462:469 a powerful approach 451:469 a powerful approach for detecting and identifying this modification 451:517 The metabolic chemical probes such as GlcNAc or GalNAc analogues bearing ketone or azide handles, in conjunction with bioorthogonal reactions, provide a powerful approach for detecting and identifying this modification. 27622469 0 35 theme Specific 30:37 arg1 Visualization 39:51 Specific Visualization 30:51 Specific Visualization 30:51 An OGA-Resistant Probe Allows Specific Visualization and Accurate Identification of O-GlcNAc-Modified Proteins in Cells. 27622469 3 36 contain have 599:602 arg1 probes 544:549 these chemical probes 529:549 these chemical probes 529:549 However, these chemical probes either enter multiple glycosylation pathways or have low labeling efficiency. 27622469 3 36 contain have 599:602 arg2 efficiency 617:626 low labeling efficiency 604:626 low labeling efficiency 604:626 However, these chemical probes either enter multiple glycosylation pathways or have low labeling efficiency. 27622469 5 37 theme salvage 872:878 arg1 pathway 880:886 the GalNAc salvage pathway 861:886 the GalNAc salvage pathway 861:886 We report here the development of a novel probe, 1,3,6-tri-O-acetyl-2-azidoacetamido-2,4-dideoxy-d-glucopyranose (Ac34dGlcNAz), that can be processed by the GalNAc salvage pathway and transferred by O-GlcNAc transferase (OGT) to O-GlcNAc proteins. 27622469 1 38 attach present 227:233 arg2 β-N-acetyl-glucosamine 130:151 O-linked β-N-acetyl-glucosamine 121:151 O-linked β-N-acetyl-glucosamine (O-GlcNAc) 121:162 O-linked β-N-acetyl-glucosamine (O-GlcNAc) is an essential and ubiquitous post-translational modification present in nucleic and cytoplasmic proteins of multicellular eukaryotes. 27622469 1 38 attach present 227:233 arg1 proteins 262:269 nucleic and cytoplasmic proteins 238:269 nucleic and cytoplasmic proteins of multicellular eukaryotes 238:297 O-linked β-N-acetyl-glucosamine (O-GlcNAc) is an essential and ubiquitous post-translational modification present in nucleic and cytoplasmic proteins of multicellular eukaryotes. 27622469 1 38 attach present 227:233 arg2 modification 214:225 an essential and ubiquitous post-translational modification 167:225 an essential and ubiquitous post-translational modification present in nucleic and cytoplasmic proteins of multicellular eukaryotes 167:297 O-linked β-N-acetyl-glucosamine (O-GlcNAc) is an essential and ubiquitous post-translational modification present in nucleic and cytoplasmic proteins of multicellular eukaryotes. 27622469 8 39 from visualization 1327:1339 arg1 cells 1356:1360 cells 1356:1360 cells 1356:1360 Combined with a click reaction, Ac34dGlcNAz allowed the selective visualization of O-GlcNAc in cells and accurate identification of O-GlcNAc-modified proteins with LC-MS/MS. 27622469 1 40 theme cytoplasmic 250:260 arg1 proteins 262:269 nucleic and cytoplasmic proteins 238:269 nucleic and cytoplasmic proteins of multicellular eukaryotes 238:297 O-linked β-N-acetyl-glucosamine (O-GlcNAc) is an essential and ubiquitous post-translational modification present in nucleic and cytoplasmic proteins of multicellular eukaryotes. 27622469 0 41 theme Accurate 57:64 arg1 Identification 66:79 Accurate Identification 57:79 Accurate Identification 57:79 An OGA-Resistant Probe Allows Specific Visualization and Accurate Identification of O-GlcNAc-Modified Proteins in Cells. 27622469 6 42 contain containing 1062:1071 arg2 glycoconjugates 1073:1087 glycoconjugates 1073:1087 glycoconjugates 1073:1087 Due to the absence of a hydroxyl group at C4, this probe is less incorporated into α/β 4-GlcNAc or GalNAc containing glycoconjugates. 27622469 6 42 contain containing 1062:1071 arg1 GalNAc 1055:1060 GalNAc 1055:1060 GalNAc containing glycoconjugates 1055:1087 Due to the absence of a hydroxyl group at C4, this probe is less incorporated into α/β 4-GlcNAc or GalNAc containing glycoconjugates. 27622469 0 43 from Identification 66:79 arg1 Cells 114:118 Cells 114:118 Cells 114:118 An OGA-Resistant Probe Allows Specific Visualization and Accurate Identification of O-GlcNAc-Modified Proteins in Cells. 27622469 5 44 theme novel 744:748 arg1 1,3,6-tri-O-acetyl-2-azidoacetamido-2,4-dideoxy-d-glucopyranose 757:819 1,3,6-tri-O-acetyl-2-azidoacetamido-2,4-dideoxy-d-glucopyranose 757:819 1,3,6-tri-O-acetyl-2-azidoacetamido-2,4-dideoxy-d-glucopyranose (Ac34dGlcNAz) 757:833 We report here the development of a novel probe, 1,3,6-tri-O-acetyl-2-azidoacetamido-2,4-dideoxy-d-glucopyranose (Ac34dGlcNAz), that can be processed by the GalNAc salvage pathway and transferred by O-GlcNAc transferase (OGT) to O-GlcNAc proteins. 27622469 5 44 theme novel 744:748 arg1 probe 750:754 a novel probe 742:754 a novel probe 742:754 We report here the development of a novel probe, 1,3,6-tri-O-acetyl-2-azidoacetamido-2,4-dideoxy-d-glucopyranose (Ac34dGlcNAz), that can be processed by the GalNAc salvage pathway and transferred by O-GlcNAc transferase (OGT) to O-GlcNAc proteins. 27622469 8 45 theme accurate 1366:1373 arg1 identification 1375:1388 accurate identification 1366:1388 accurate identification of O-GlcNAc-modified proteins with LC-MS/MS 1366:1432 Combined with a click reaction, Ac34dGlcNAz allowed the selective visualization of O-GlcNAc in cells and accurate identification of O-GlcNAc-modified proteins with LC-MS/MS. 27622469 9 46 theme potent 1464:1469 arg1 tool 1485:1488 a more potent and selective tool 1457:1488 a more potent and selective tool in tracking 1457:1500 This probe represents a more potent and selective tool in tracking, capturing, and identifying O-GlcNAc-modified proteins in cells and cell lysates. 27622469 6 47 from C4 998:999 arg1 absence 967:973 the absence 963:973 the absence of a hydroxyl group at C4 963:999 Due to the absence of a hydroxyl group at C4, this probe is less incorporated into α/β 4-GlcNAc or GalNAc containing glycoconjugates. 27622469 6 47 from C4 998:999 arg1 group 989:993 a hydroxyl group 978:993 a hydroxyl group at C4 978:999 Due to the absence of a hydroxyl group at C4, this probe is less incorporated into α/β 4-GlcNAc or GalNAc containing glycoconjugates. 27622469 1 48 from proteins 262:269 arg1 present 227:233 present 227:233 present 227:233 O-linked β-N-acetyl-glucosamine (O-GlcNAc) is an essential and ubiquitous post-translational modification present in nucleic and cytoplasmic proteins of multicellular eukaryotes. 27622469 2 49 theme chemical 314:321 arg1 probes 323:328 The metabolic chemical probes 300:328 The metabolic chemical probes such as GlcNAc or GalNAc analogues bearing ketone or azide 300:387 The metabolic chemical probes such as GlcNAc or GalNAc analogues bearing ketone or azide handles, in conjunction with bioorthogonal reactions, provide a powerful approach for detecting and identifying this modification. 27622469 2 49 theme chemical 314:321 arg1 analogues 355:363 GlcNAc or GalNAc analogues 338:363 GlcNAc or GalNAc analogues bearing ketone or azide 338:387 The metabolic chemical probes such as GlcNAc or GalNAc analogues bearing ketone or azide handles, in conjunction with bioorthogonal reactions, provide a powerful approach for detecting and identifying this modification. 27622469 2 50 dep handles 389:395 arg1 provide 443:449 provide 443:449 provide a powerful approach for detecting and identifying this modification 443:517 The metabolic chemical probes such as GlcNAc or GalNAc analogues bearing ketone or azide handles, in conjunction with bioorthogonal reactions, provide a powerful approach for detecting and identifying this modification. 27622469 9 51 theme selective 1475:1483 arg1 tool 1485:1488 a more potent and selective tool 1457:1488 a more potent and selective tool in tracking 1457:1500 This probe represents a more potent and selective tool in tracking, capturing, and identifying O-GlcNAc-modified proteins in cells and cell lysates. 27622469 5 52 theme probe 750:754 arg1 development 727:737 the development 723:737 the development of a novel probe, 1,3,6-tri-O-acetyl-2-azidoacetamido-2,4-dideoxy-d-glucopyranose (Ac34dGlcNAz), that can be processed by the GalNAc salvage pathway and transferred by O-GlcNAc transferase (OGT) to O-GlcNAc proteins 723:953 We report here the development of a novel probe, 1,3,6-tri-O-acetyl-2-azidoacetamido-2,4-dideoxy-d-glucopyranose (Ac34dGlcNAz), that can be processed by the GalNAc salvage pathway and transferred by O-GlcNAc transferase (OGT) to O-GlcNAc proteins. 27622469 8 53 with proteins 1411:1418 arg1 LC-MS/MS 1425:1432 LC-MS/MS 1425:1432 LC-MS/MS 1425:1432 Combined with a click reaction, Ac34dGlcNAz allowed the selective visualization of O-GlcNAc in cells and accurate identification of O-GlcNAc-modified proteins with LC-MS/MS. 27622469 2 54 theme metabolic 304:312 arg1 probes 323:328 The metabolic chemical probes 300:328 The metabolic chemical probes such as GlcNAc or GalNAc analogues bearing ketone or azide 300:387 The metabolic chemical probes such as GlcNAc or GalNAc analogues bearing ketone or azide handles, in conjunction with bioorthogonal reactions, provide a powerful approach for detecting and identifying this modification. 27622469 2 54 theme metabolic 304:312 arg1 analogues 355:363 GlcNAc or GalNAc analogues 338:363 GlcNAc or GalNAc analogues bearing ketone or azide 338:387 The metabolic chemical probes such as GlcNAc or GalNAc analogues bearing ketone or azide handles, in conjunction with bioorthogonal reactions, provide a powerful approach for detecting and identifying this modification. 27622469 9 55 from proteins 1548:1555 arg1 cells 1560:1564 cells 1560:1564 cells 1560:1564 This probe represents a more potent and selective tool in tracking, capturing, and identifying O-GlcNAc-modified proteins in cells and cell lysates. 27622469 9 55 from proteins 1548:1555 arg1 lysates 1575:1581 cell lysates 1570:1581 cell lysates 1570:1581 This probe represents a more potent and selective tool in tracking, capturing, and identifying O-GlcNAc-modified proteins in cells and cell lysates. 27622469 3 56 theme chemical 535:542 arg1 probes 544:549 these chemical probes 529:549 these chemical probes 529:549 However, these chemical probes either enter multiple glycosylation pathways or have low labeling efficiency. 27622469 8 57 theme click 1277:1281 arg1 reaction 1283:1290 a click reaction 1275:1290 a click reaction 1275:1290 Combined with a click reaction, Ac34dGlcNAz allowed the selective visualization of O-GlcNAc in cells and accurate identification of O-GlcNAc-modified proteins with LC-MS/MS. 27622469 2 58 with conjunction 401:411 arg1 reactions 432:440 bioorthogonal reactions 418:440 bioorthogonal reactions 418:440 The metabolic chemical probes such as GlcNAc or GalNAc analogues bearing ketone or azide handles, in conjunction with bioorthogonal reactions, provide a powerful approach for detecting and identifying this modification. 27622469 1 59 from present 227:233 arg1 proteins 262:269 nucleic and cytoplasmic proteins 238:269 nucleic and cytoplasmic proteins of multicellular eukaryotes 238:297 O-linked β-N-acetyl-glucosamine (O-GlcNAc) is an essential and ubiquitous post-translational modification present in nucleic and cytoplasmic proteins of multicellular eukaryotes. 27622469 3 60 theme glycosylation 573:585 arg1 pathways 587:594 multiple glycosylation pathways 564:594 multiple glycosylation pathways 564:594 However, these chemical probes either enter multiple glycosylation pathways or have low labeling efficiency. 27622469 9 61 theme O-GlcNAc-modified 1530:1546 arg1 proteins 1548:1555 O-GlcNAc-modified proteins 1530:1555 O-GlcNAc-modified proteins in cells and cell lysates 1530:1581 This probe represents a more potent and selective tool in tracking, capturing, and identifying O-GlcNAc-modified proteins in cells and cell lysates. 27622469 1 62 theme multicellular 274:286 arg1 eukaryotes 288:297 multicellular eukaryotes 274:297 multicellular eukaryotes 274:297 O-linked β-N-acetyl-glucosamine (O-GlcNAc) is an essential and ubiquitous post-translational modification present in nucleic and cytoplasmic proteins of multicellular eukaryotes. 27622469 1 63 link O-linked 121:128 arg1 O-GlcNAc 154:161 O-GlcNAc 154:161 O-GlcNAc 154:161 O-linked β-N-acetyl-glucosamine (O-GlcNAc) is an essential and ubiquitous post-translational modification present in nucleic and cytoplasmic proteins of multicellular eukaryotes. 27622469 1 63 link O-linked 121:128 arg1 modification 214:225 an essential and ubiquitous post-translational modification 167:225 an essential and ubiquitous post-translational modification present in nucleic and cytoplasmic proteins of multicellular eukaryotes 167:297 O-linked β-N-acetyl-glucosamine (O-GlcNAc) is an essential and ubiquitous post-translational modification present in nucleic and cytoplasmic proteins of multicellular eukaryotes. 27622469 1 63 link O-linked 121:128 arg1 β-N-acetyl-glucosamine 130:151 O-linked β-N-acetyl-glucosamine 121:151 O-linked β-N-acetyl-glucosamine (O-GlcNAc) 121:162 O-linked β-N-acetyl-glucosamine (O-GlcNAc) is an essential and ubiquitous post-translational modification present in nucleic and cytoplasmic proteins of multicellular eukaryotes. 27622469 3 64 theme low 604:606 arg1 efficiency 617:626 low labeling efficiency 604:626 low labeling efficiency 604:626 However, these chemical probes either enter multiple glycosylation pathways or have low labeling efficiency. 27622469 8 65 theme O-GlcNAc-modified 1393:1409 arg1 proteins 1411:1418 O-GlcNAc-modified proteins 1393:1418 O-GlcNAc-modified proteins with LC-MS/MS 1393:1432 Combined with a click reaction, Ac34dGlcNAz allowed the selective visualization of O-GlcNAc in cells and accurate identification of O-GlcNAc-modified proteins with LC-MS/MS. 27622469 1 66 theme eukaryotes 288:297 arg1 proteins 262:269 nucleic and cytoplasmic proteins 238:269 nucleic and cytoplasmic proteins of multicellular eukaryotes 238:297 O-linked β-N-acetyl-glucosamine (O-GlcNAc) is an essential and ubiquitous post-translational modification present in nucleic and cytoplasmic proteins of multicellular eukaryotes. 26773002 0 0 theme signaling 84:92 arg1 pathways 94:101 multiple signaling pathways 75:101 multiple signaling pathways 75:101 O-GlcNAcylation of master growth repressor DELLA by SECRET AGENT modulates multiple signaling pathways in Arabidopsis. 26773002 4 1 theme SECRET 715:720 arg1 AGENT 722:726 the O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) SECRET AGENT 653:726 the O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) SECRET AGENT (SEC) in Arabidopsis 653:747 Here, we show that DELLAs are modified by the O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) SECRET AGENT (SEC) in Arabidopsis. 26773002 4 1 theme SECRET 715:720 arg1 SEC 729:731 SEC 729:731 SEC 729:731 Here, we show that DELLAs are modified by the O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) SECRET AGENT (SEC) in Arabidopsis. 26773002 5 2 theme REPRESSOR 787:795 arg1 O-GlcNAcylation 750:764 O-GlcNAcylation 750:764 O-GlcNAcylation of the DELLA protein REPRESSOR OF ga1-3 (RGA) 750:810 O-GlcNAcylation of the DELLA protein REPRESSOR OF ga1-3 (RGA) inhibits RGA binding to four of its interactors-PHYTOCHROME-INTERACTING FACTOR3 (PIF3), PIF4, JASMONATE-ZIM DOMAIN1, and BRASSINAZOLE-RESISTANT1 (BZR1)-that are key regulators in light, jasmonate, and brassinosteroid signaling pathways, respectively. 26773002 4 3 from AGENT 722:726 arg1 Arabidopsis 737:747 Arabidopsis 737:747 Arabidopsis 737:747 Here, we show that DELLAs are modified by the O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) SECRET AGENT (SEC) in Arabidopsis. 26773002 0 4 theme multiple 75:82 arg1 pathways 94:101 multiple signaling pathways 75:101 multiple signaling pathways 75:101 O-GlcNAcylation of master growth repressor DELLA by SECRET AGENT modulates multiple signaling pathways in Arabidopsis. 26773002 5 5 theme JASMONATE-ZIM 906:918 arg1 FACTOR3 884:890 its interactors-PHYTOCHROME-INTERACTING FACTOR3 844:890 its interactors-PHYTOCHROME-INTERACTING FACTOR3 (PIF3) 844:897 O-GlcNAcylation of the DELLA protein REPRESSOR OF ga1-3 (RGA) inhibits RGA binding to four of its interactors-PHYTOCHROME-INTERACTING FACTOR3 (PIF3), PIF4, JASMONATE-ZIM DOMAIN1, and BRASSINAZOLE-RESISTANT1 (BZR1)-that are key regulators in light, jasmonate, and brassinosteroid signaling pathways, respectively. 26773002 5 5 theme JASMONATE-ZIM 906:918 arg1 DOMAIN1 920:926 JASMONATE-ZIM DOMAIN1 906:926 JASMONATE-ZIM DOMAIN1 906:926 O-GlcNAcylation of the DELLA protein REPRESSOR OF ga1-3 (RGA) inhibits RGA binding to four of its interactors-PHYTOCHROME-INTERACTING FACTOR3 (PIF3), PIF4, JASMONATE-ZIM DOMAIN1, and BRASSINAZOLE-RESISTANT1 (BZR1)-that are key regulators in light, jasmonate, and brassinosteroid signaling pathways, respectively. 26773002 7 6 theme DELLAs 1355:1360 arg1 O-GlcNAcylation 1336:1350 O-GlcNAcylation 1336:1350 O-GlcNAcylation of DELLAs 1336:1360 Our results reveal a direct role of OGT in repressing DELLA activity and indicate that O-GlcNAcylation of DELLAs provides a fine-tuning mechanism in coordinating multiple signaling activities during plant development. 26773002 6 7 theme BZR1 1233:1236 arg1 genes 1216:1220 several common target genes 1194:1220 several common target genes of DELLAs, BZR1, and PIFs 1194:1246 Consistent with this, the sec-null mutant displayed reduced responses to GA and brassinosteroid and showed decreased expression of several common target genes of DELLAs, BZR1, and PIFs. 26773002 6 8 theme common 1202:1207 arg1 genes 1216:1220 several common target genes 1194:1220 several common target genes of DELLAs, BZR1, and PIFs 1194:1246 Consistent with this, the sec-null mutant displayed reduced responses to GA and brassinosteroid and showed decreased expression of several common target genes of DELLAs, BZR1, and PIFs. 26773002 4 9 theme transferase 697:707 arg1 AGENT 722:726 the O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) SECRET AGENT 653:726 the O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) SECRET AGENT (SEC) in Arabidopsis 653:747 Here, we show that DELLAs are modified by the O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) SECRET AGENT (SEC) in Arabidopsis. 26773002 4 9 theme transferase 697:707 arg1 SEC 729:731 SEC 729:731 SEC 729:731 Here, we show that DELLAs are modified by the O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) SECRET AGENT (SEC) in Arabidopsis. 26773002 7 10 theme multiple 1411:1418 arg1 activities 1430:1439 multiple signaling activities 1411:1439 multiple signaling activities 1411:1439 Our results reveal a direct role of OGT in repressing DELLA activity and indicate that O-GlcNAcylation of DELLAs provides a fine-tuning mechanism in coordinating multiple signaling activities during plant development. 26773002 6 11 theme several 1194:1200 arg1 genes 1216:1220 several common target genes 1194:1220 several common target genes of DELLAs, BZR1, and PIFs 1194:1246 Consistent with this, the sec-null mutant displayed reduced responses to GA and brassinosteroid and showed decreased expression of several common target genes of DELLAs, BZR1, and PIFs. 26773002 5 12 theme key 973:975 arg1 -that 963:967 BRASSINAZOLE-RESISTANT1 (BZR1)-that 933:967 BRASSINAZOLE-RESISTANT1 (BZR1)-that 933:967 O-GlcNAcylation of the DELLA protein REPRESSOR OF ga1-3 (RGA) inhibits RGA binding to four of its interactors-PHYTOCHROME-INTERACTING FACTOR3 (PIF3), PIF4, JASMONATE-ZIM DOMAIN1, and BRASSINAZOLE-RESISTANT1 (BZR1)-that are key regulators in light, jasmonate, and brassinosteroid signaling pathways, respectively. 26773002 5 12 theme key 973:975 arg1 regulators 977:986 key regulators 973:986 key regulators in light, jasmonate, and brassinosteroid signaling pathways, respectively 973:1060 O-GlcNAcylation of the DELLA protein REPRESSOR OF ga1-3 (RGA) inhibits RGA binding to four of its interactors-PHYTOCHROME-INTERACTING FACTOR3 (PIF3), PIF4, JASMONATE-ZIM DOMAIN1, and BRASSINAZOLE-RESISTANT1 (BZR1)-that are key regulators in light, jasmonate, and brassinosteroid signaling pathways, respectively. 26773002 5 13 theme BRASSINAZOLE-RESISTANT1 933:955 arg1 -that 963:967 BRASSINAZOLE-RESISTANT1 (BZR1)-that 933:967 BRASSINAZOLE-RESISTANT1 (BZR1)-that 933:967 O-GlcNAcylation of the DELLA protein REPRESSOR OF ga1-3 (RGA) inhibits RGA binding to four of its interactors-PHYTOCHROME-INTERACTING FACTOR3 (PIF3), PIF4, JASMONATE-ZIM DOMAIN1, and BRASSINAZOLE-RESISTANT1 (BZR1)-that are key regulators in light, jasmonate, and brassinosteroid signaling pathways, respectively. 26773002 5 13 theme BRASSINAZOLE-RESISTANT1 933:955 arg1 regulators 977:986 key regulators 973:986 key regulators in light, jasmonate, and brassinosteroid signaling pathways, respectively 973:1060 O-GlcNAcylation of the DELLA protein REPRESSOR OF ga1-3 (RGA) inhibits RGA binding to four of its interactors-PHYTOCHROME-INTERACTING FACTOR3 (PIF3), PIF4, JASMONATE-ZIM DOMAIN1, and BRASSINAZOLE-RESISTANT1 (BZR1)-that are key regulators in light, jasmonate, and brassinosteroid signaling pathways, respectively. 26773002 7 14 theme direct 1270:1275 arg1 role 1277:1280 a direct role 1268:1280 a direct role of OGT in repressing DELLA activity 1268:1316 Our results reveal a direct role of OGT in repressing DELLA activity and indicate that O-GlcNAcylation of DELLAs provides a fine-tuning mechanism in coordinating multiple signaling activities during plant development. 26773002 4 15 theme O-linked 657:664 arg1 O-GlcNAc 687:694 O-GlcNAc 687:694 O-GlcNAc 687:694 Here, we show that DELLAs are modified by the O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) SECRET AGENT (SEC) in Arabidopsis. 26773002 4 15 theme O-linked 657:664 arg1 N-acetylglucosamine 666:684 the O-linked N-acetylglucosamine 653:684 the O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) SECRET AGENT (SEC) in Arabidopsis 653:747 Here, we show that DELLAs are modified by the O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) SECRET AGENT (SEC) in Arabidopsis. 26773002 7 16 theme DELLA 1303:1307 arg1 activity 1309:1316 DELLA activity 1303:1316 DELLA activity 1303:1316 Our results reveal a direct role of OGT in repressing DELLA activity and indicate that O-GlcNAcylation of DELLAs provides a fine-tuning mechanism in coordinating multiple signaling activities during plant development. 26773002 1 17 theme master 177:182 arg1 repressors 191:200 master growth repressors 177:200 master growth repressors in plants 177:210 The DELLA family of transcription regulators functions as master growth repressors in plants by inhibiting phytohormone gibberellin (GA) signaling in response to developmental and environmental cues. 26773002 1 17 theme master 177:182 arg1 family 129:134 The DELLA family 119:134 The DELLA family of transcription regulators 119:162 The DELLA family of transcription regulators functions as master growth repressors in plants by inhibiting phytohormone gibberellin (GA) signaling in response to developmental and environmental cues. 26773002 4 18 mod modified 641:648 arg3 AGENT 722:726 the O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) SECRET AGENT 653:726 the O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) SECRET AGENT (SEC) in Arabidopsis 653:747 Here, we show that DELLAs are modified by the O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) SECRET AGENT (SEC) in Arabidopsis. 26773002 4 18 mod modified 641:648 arg1 DELLAs 630:635 DELLAs 630:635 DELLAs 630:635 Here, we show that DELLAs are modified by the O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) SECRET AGENT (SEC) in Arabidopsis. 26773002 4 18 mod modified 641:648 arg3 SEC 729:731 SEC 729:731 SEC 729:731 Here, we show that DELLAs are modified by the O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) SECRET AGENT (SEC) in Arabidopsis. 26773002 2 19 with interactions 439:450 arg1 factors 475:481 key transcription factors 457:481 key transcription factors 457:481 DELLAs also play a central role in mediating cross-talk between GA and other signaling pathways via antagonistic direct interactions with key transcription factors. 26773002 5 20 theme ga1-3 800:804 arg1 REPRESSOR 787:795 the DELLA protein REPRESSOR 769:795 the DELLA protein REPRESSOR OF ga1-3 (RGA) 769:810 O-GlcNAcylation of the DELLA protein REPRESSOR OF ga1-3 (RGA) inhibits RGA binding to four of its interactors-PHYTOCHROME-INTERACTING FACTOR3 (PIF3), PIF4, JASMONATE-ZIM DOMAIN1, and BRASSINAZOLE-RESISTANT1 (BZR1)-that are key regulators in light, jasmonate, and brassinosteroid signaling pathways, respectively. 26773002 3 21 theme plant 576:580 arg1 development 582:592 plant development 576:592 plant development 576:592 However, how these crucial protein-protein interactions can be dynamically regulated during plant development remains unclear. 26773002 1 22 theme growth 184:189 arg1 repressors 191:200 master growth repressors 177:200 master growth repressors in plants 177:210 The DELLA family of transcription regulators functions as master growth repressors in plants by inhibiting phytohormone gibberellin (GA) signaling in response to developmental and environmental cues. 26773002 1 22 theme growth 184:189 arg1 family 129:134 The DELLA family 119:134 The DELLA family of transcription regulators 119:162 The DELLA family of transcription regulators functions as master growth repressors in plants by inhibiting phytohormone gibberellin (GA) signaling in response to developmental and environmental cues. 26773002 6 23 theme decreased 1170:1178 arg1 expression 1180:1189 decreased expression 1170:1189 decreased expression of several common target genes of DELLAs, BZR1, and PIFs 1170:1246 Consistent with this, the sec-null mutant displayed reduced responses to GA and brassinosteroid and showed decreased expression of several common target genes of DELLAs, BZR1, and PIFs. 26773002 2 24 theme other 390:394 arg1 pathways 406:413 other signaling pathways 390:413 other signaling pathways 390:413 DELLAs also play a central role in mediating cross-talk between GA and other signaling pathways via antagonistic direct interactions with key transcription factors. 26773002 2 25 theme transcription 461:473 arg1 factors 475:481 key transcription factors 457:481 key transcription factors 457:481 DELLAs also play a central role in mediating cross-talk between GA and other signaling pathways via antagonistic direct interactions with key transcription factors. 26773002 1 26 theme developmental 281:293 arg1 cues 313:316 developmental and environmental cues 281:316 developmental and environmental cues 281:316 The DELLA family of transcription regulators functions as master growth repressors in plants by inhibiting phytohormone gibberellin (GA) signaling in response to developmental and environmental cues. 26773002 6 27 theme PIFs 1243:1246 arg1 genes 1216:1220 several common target genes 1194:1220 several common target genes of DELLAs, BZR1, and PIFs 1194:1246 Consistent with this, the sec-null mutant displayed reduced responses to GA and brassinosteroid and showed decreased expression of several common target genes of DELLAs, BZR1, and PIFs. 26773002 5 28 theme FACTOR3 884:890 arg1 DOMAIN1 920:926 JASMONATE-ZIM DOMAIN1 906:926 JASMONATE-ZIM DOMAIN1 906:926 O-GlcNAcylation of the DELLA protein REPRESSOR OF ga1-3 (RGA) inhibits RGA binding to four of its interactors-PHYTOCHROME-INTERACTING FACTOR3 (PIF3), PIF4, JASMONATE-ZIM DOMAIN1, and BRASSINAZOLE-RESISTANT1 (BZR1)-that are key regulators in light, jasmonate, and brassinosteroid signaling pathways, respectively. 26773002 5 28 theme FACTOR3 884:890 arg1 four 836:839 four 836:839 four 836:839 O-GlcNAcylation of the DELLA protein REPRESSOR OF ga1-3 (RGA) inhibits RGA binding to four of its interactors-PHYTOCHROME-INTERACTING FACTOR3 (PIF3), PIF4, JASMONATE-ZIM DOMAIN1, and BRASSINAZOLE-RESISTANT1 (BZR1)-that are key regulators in light, jasmonate, and brassinosteroid signaling pathways, respectively. 26773002 5 28 theme FACTOR3 884:890 arg1 PIF3 893:896 PIF3 893:896 PIF3 893:896 O-GlcNAcylation of the DELLA protein REPRESSOR OF ga1-3 (RGA) inhibits RGA binding to four of its interactors-PHYTOCHROME-INTERACTING FACTOR3 (PIF3), PIF4, JASMONATE-ZIM DOMAIN1, and BRASSINAZOLE-RESISTANT1 (BZR1)-that are key regulators in light, jasmonate, and brassinosteroid signaling pathways, respectively. 26773002 5 28 theme FACTOR3 884:890 arg1 PIF4 900:903 PIF4 900:903 PIF4 900:903 O-GlcNAcylation of the DELLA protein REPRESSOR OF ga1-3 (RGA) inhibits RGA binding to four of its interactors-PHYTOCHROME-INTERACTING FACTOR3 (PIF3), PIF4, JASMONATE-ZIM DOMAIN1, and BRASSINAZOLE-RESISTANT1 (BZR1)-that are key regulators in light, jasmonate, and brassinosteroid signaling pathways, respectively. 26773002 5 28 theme FACTOR3 884:890 arg1 FACTOR3 884:890 its interactors-PHYTOCHROME-INTERACTING FACTOR3 844:890 its interactors-PHYTOCHROME-INTERACTING FACTOR3 (PIF3) 844:897 O-GlcNAcylation of the DELLA protein REPRESSOR OF ga1-3 (RGA) inhibits RGA binding to four of its interactors-PHYTOCHROME-INTERACTING FACTOR3 (PIF3), PIF4, JASMONATE-ZIM DOMAIN1, and BRASSINAZOLE-RESISTANT1 (BZR1)-that are key regulators in light, jasmonate, and brassinosteroid signaling pathways, respectively. 26773002 5 29 theme BZR1 958:961 arg1 -that 963:967 BRASSINAZOLE-RESISTANT1 (BZR1)-that 933:967 BRASSINAZOLE-RESISTANT1 (BZR1)-that 933:967 O-GlcNAcylation of the DELLA protein REPRESSOR OF ga1-3 (RGA) inhibits RGA binding to four of its interactors-PHYTOCHROME-INTERACTING FACTOR3 (PIF3), PIF4, JASMONATE-ZIM DOMAIN1, and BRASSINAZOLE-RESISTANT1 (BZR1)-that are key regulators in light, jasmonate, and brassinosteroid signaling pathways, respectively. 26773002 5 29 theme BZR1 958:961 arg1 regulators 977:986 key regulators 973:986 key regulators in light, jasmonate, and brassinosteroid signaling pathways, respectively 973:1060 O-GlcNAcylation of the DELLA protein REPRESSOR OF ga1-3 (RGA) inhibits RGA binding to four of its interactors-PHYTOCHROME-INTERACTING FACTOR3 (PIF3), PIF4, JASMONATE-ZIM DOMAIN1, and BRASSINAZOLE-RESISTANT1 (BZR1)-that are key regulators in light, jasmonate, and brassinosteroid signaling pathways, respectively. 26773002 0 30 theme growth 26:31 arg1 DELLA 43:47 master growth repressor DELLA 19:47 master growth repressor DELLA 19:47 O-GlcNAcylation of master growth repressor DELLA by SECRET AGENT modulates multiple signaling pathways in Arabidopsis. 26773002 5 31 theme RGA 821:823 arg1 binding 825:831 RGA binding 821:831 RGA binding to four of its interactors-PHYTOCHROME-INTERACTING FACTOR3 (PIF3), PIF4, JASMONATE-ZIM DOMAIN1 821:926 O-GlcNAcylation of the DELLA protein REPRESSOR OF ga1-3 (RGA) inhibits RGA binding to four of its interactors-PHYTOCHROME-INTERACTING FACTOR3 (PIF3), PIF4, JASMONATE-ZIM DOMAIN1, and BRASSINAZOLE-RESISTANT1 (BZR1)-that are key regulators in light, jasmonate, and brassinosteroid signaling pathways, respectively. 26773002 4 32 theme N-acetylglucosamine 666:684 arg1 transferase 697:707 the O-linked N-acetylglucosamine (O-GlcNAc) transferase 653:707 the O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) SECRET AGENT (SEC) in Arabidopsis 653:747 Here, we show that DELLAs are modified by the O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) SECRET AGENT (SEC) in Arabidopsis. 26773002 4 32 theme N-acetylglucosamine 666:684 arg1 OGT 710:712 OGT 710:712 OGT 710:712 Here, we show that DELLAs are modified by the O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) SECRET AGENT (SEC) in Arabidopsis. 26773002 0 33 theme master 19:24 arg1 DELLA 43:47 master growth repressor DELLA 19:47 master growth repressor DELLA 19:47 O-GlcNAcylation of master growth repressor DELLA by SECRET AGENT modulates multiple signaling pathways in Arabidopsis. 26773002 1 34 theme environmental 299:311 arg1 cues 313:316 developmental and environmental cues 281:316 developmental and environmental cues 281:316 The DELLA family of transcription regulators functions as master growth repressors in plants by inhibiting phytohormone gibberellin (GA) signaling in response to developmental and environmental cues. 26773002 6 35 theme sec-null 1089:1096 arg1 mutant 1098:1103 the sec-null mutant 1085:1103 the sec-null mutant 1085:1103 Consistent with this, the sec-null mutant displayed reduced responses to GA and brassinosteroid and showed decreased expression of several common target genes of DELLAs, BZR1, and PIFs. 26773002 2 36 theme direct 432:437 arg1 interactions 439:450 antagonistic direct interactions 419:450 antagonistic direct interactions with key transcription factors 419:481 DELLAs also play a central role in mediating cross-talk between GA and other signaling pathways via antagonistic direct interactions with key transcription factors. 26773002 0 37 theme DELLA 43:47 arg1 O-GlcNAcylation 0:14 O-GlcNAcylation 0:14 O-GlcNAcylation of master growth repressor DELLA by SECRET AGENT 0:63 O-GlcNAcylation of master growth repressor DELLA by SECRET AGENT modulates multiple signaling pathways in Arabidopsis. 26773002 7 38 theme OGT 1285:1287 arg1 role 1277:1280 a direct role 1268:1280 a direct role of OGT in repressing DELLA activity 1268:1316 Our results reveal a direct role of OGT in repressing DELLA activity and indicate that O-GlcNAcylation of DELLAs provides a fine-tuning mechanism in coordinating multiple signaling activities during plant development. 26773002 1 39 from signaling 256:264 arg1 response 269:276 response 269:276 response to developmental and environmental cues 269:316 The DELLA family of transcription regulators functions as master growth repressors in plants by inhibiting phytohormone gibberellin (GA) signaling in response to developmental and environmental cues. 26773002 7 40 theme fine-tuning 1373:1383 arg1 mechanism 1385:1393 a fine-tuning mechanism 1371:1393 a fine-tuning mechanism in coordinating multiple signaling activities during plant development 1371:1464 Our results reveal a direct role of OGT in repressing DELLA activity and indicate that O-GlcNAcylation of DELLAs provides a fine-tuning mechanism in coordinating multiple signaling activities during plant development. 26773002 2 41 theme antagonistic 419:430 arg1 interactions 439:450 antagonistic direct interactions 419:450 antagonistic direct interactions with key transcription factors 419:481 DELLAs also play a central role in mediating cross-talk between GA and other signaling pathways via antagonistic direct interactions with key transcription factors. 26773002 0 42 theme repressor 33:41 arg1 DELLA 43:47 master growth repressor DELLA 19:47 master growth repressor DELLA 19:47 O-GlcNAcylation of master growth repressor DELLA by SECRET AGENT modulates multiple signaling pathways in Arabidopsis. 26773002 2 43 theme key 457:459 arg1 factors 475:481 key transcription factors 457:481 key transcription factors 457:481 DELLAs also play a central role in mediating cross-talk between GA and other signaling pathways via antagonistic direct interactions with key transcription factors. 26773002 1 44 theme phytohormone 226:237 arg1 GA 252:253 GA 252:253 GA 252:253 The DELLA family of transcription regulators functions as master growth repressors in plants by inhibiting phytohormone gibberellin (GA) signaling in response to developmental and environmental cues. 26773002 1 44 theme phytohormone 226:237 arg1 gibberellin 239:249 phytohormone gibberellin 226:249 phytohormone gibberellin (GA) signaling in response to developmental and environmental cues 226:316 The DELLA family of transcription regulators functions as master growth repressors in plants by inhibiting phytohormone gibberellin (GA) signaling in response to developmental and environmental cues. 26773002 0 45 theme SECRET 52:57 arg1 AGENT 59:63 SECRET AGENT 52:63 SECRET AGENT 52:63 O-GlcNAcylation of master growth repressor DELLA by SECRET AGENT modulates multiple signaling pathways in Arabidopsis. 26773002 5 46 theme signaling 1029:1037 arg1 pathways 1039:1046 brassinosteroid signaling pathways 1013:1046 brassinosteroid signaling pathways 1013:1046 O-GlcNAcylation of the DELLA protein REPRESSOR OF ga1-3 (RGA) inhibits RGA binding to four of its interactors-PHYTOCHROME-INTERACTING FACTOR3 (PIF3), PIF4, JASMONATE-ZIM DOMAIN1, and BRASSINAZOLE-RESISTANT1 (BZR1)-that are key regulators in light, jasmonate, and brassinosteroid signaling pathways, respectively. 26773002 6 47 theme reduced 1115:1121 arg1 responses 1123:1131 reduced responses 1115:1131 reduced responses to GA and brassinosteroid 1115:1157 Consistent with this, the sec-null mutant displayed reduced responses to GA and brassinosteroid and showed decreased expression of several common target genes of DELLAs, BZR1, and PIFs. 26773002 3 48 theme protein-protein 511:525 arg1 interactions 527:538 these crucial protein-protein interactions 497:538 these crucial protein-protein interactions 497:538 However, how these crucial protein-protein interactions can be dynamically regulated during plant development remains unclear. 26773002 1 49 theme DELLA 123:127 arg1 family 129:134 The DELLA family 119:134 The DELLA family of transcription regulators 119:162 The DELLA family of transcription regulators functions as master growth repressors in plants by inhibiting phytohormone gibberellin (GA) signaling in response to developmental and environmental cues. 26773002 1 49 theme DELLA 123:127 arg1 repressors 191:200 master growth repressors 177:200 master growth repressors in plants 177:210 The DELLA family of transcription regulators functions as master growth repressors in plants by inhibiting phytohormone gibberellin (GA) signaling in response to developmental and environmental cues. 26773002 6 50 theme target 1209:1214 arg1 genes 1216:1220 several common target genes 1194:1220 several common target genes of DELLAs, BZR1, and PIFs 1194:1246 Consistent with this, the sec-null mutant displayed reduced responses to GA and brassinosteroid and showed decreased expression of several common target genes of DELLAs, BZR1, and PIFs. 26773002 6 51 theme DELLAs 1225:1230 arg1 genes 1216:1220 several common target genes 1194:1220 several common target genes of DELLAs, BZR1, and PIFs 1194:1246 Consistent with this, the sec-null mutant displayed reduced responses to GA and brassinosteroid and showed decreased expression of several common target genes of DELLAs, BZR1, and PIFs. 26773002 5 52 theme brassinosteroid 1013:1027 arg1 pathways 1039:1046 brassinosteroid signaling pathways 1013:1046 brassinosteroid signaling pathways 1013:1046 O-GlcNAcylation of the DELLA protein REPRESSOR OF ga1-3 (RGA) inhibits RGA binding to four of its interactors-PHYTOCHROME-INTERACTING FACTOR3 (PIF3), PIF4, JASMONATE-ZIM DOMAIN1, and BRASSINAZOLE-RESISTANT1 (BZR1)-that are key regulators in light, jasmonate, and brassinosteroid signaling pathways, respectively. 26773002 2 53 theme central 338:344 arg1 role 346:349 a central role 336:349 a central role 336:349 DELLAs also play a central role in mediating cross-talk between GA and other signaling pathways via antagonistic direct interactions with key transcription factors. 26773002 1 54 theme gibberellin 239:249 arg1 signaling 256:264 phytohormone gibberellin (GA) signaling 226:264 phytohormone gibberellin (GA) signaling in response to developmental and environmental cues 226:316 The DELLA family of transcription regulators functions as master growth repressors in plants by inhibiting phytohormone gibberellin (GA) signaling in response to developmental and environmental cues. 26773002 7 55 theme signaling 1420:1428 arg1 activities 1430:1439 multiple signaling activities 1411:1439 multiple signaling activities 1411:1439 Our results reveal a direct role of OGT in repressing DELLA activity and indicate that O-GlcNAcylation of DELLAs provides a fine-tuning mechanism in coordinating multiple signaling activities during plant development. 26773002 6 56 with Consistent 1063:1072 arg1 this 1079:1082 this 1079:1082 this 1079:1082 Consistent with this, the sec-null mutant displayed reduced responses to GA and brassinosteroid and showed decreased expression of several common target genes of DELLAs, BZR1, and PIFs. 26773002 7 57 theme plant 1448:1452 arg1 development 1454:1464 plant development 1448:1464 plant development 1448:1464 Our results reveal a direct role of OGT in repressing DELLA activity and indicate that O-GlcNAcylation of DELLAs provides a fine-tuning mechanism in coordinating multiple signaling activities during plant development. 26773002 1 58 from repressors 191:200 arg1 plants 205:210 plants 205:210 plants 205:210 The DELLA family of transcription regulators functions as master growth repressors in plants by inhibiting phytohormone gibberellin (GA) signaling in response to developmental and environmental cues. 26773002 3 59 theme crucial 503:509 arg1 interactions 527:538 these crucial protein-protein interactions 497:538 these crucial protein-protein interactions 497:538 However, how these crucial protein-protein interactions can be dynamically regulated during plant development remains unclear. 26773002 5 60 theme DELLA 773:777 arg1 REPRESSOR 787:795 the DELLA protein REPRESSOR 769:795 the DELLA protein REPRESSOR OF ga1-3 (RGA) 769:810 O-GlcNAcylation of the DELLA protein REPRESSOR OF ga1-3 (RGA) inhibits RGA binding to four of its interactors-PHYTOCHROME-INTERACTING FACTOR3 (PIF3), PIF4, JASMONATE-ZIM DOMAIN1, and BRASSINAZOLE-RESISTANT1 (BZR1)-that are key regulators in light, jasmonate, and brassinosteroid signaling pathways, respectively. 26773002 5 61 theme interactors-PHYTOCHROME-INTERACTING 848:882 arg1 DOMAIN1 920:926 JASMONATE-ZIM DOMAIN1 906:926 JASMONATE-ZIM DOMAIN1 906:926 O-GlcNAcylation of the DELLA protein REPRESSOR OF ga1-3 (RGA) inhibits RGA binding to four of its interactors-PHYTOCHROME-INTERACTING FACTOR3 (PIF3), PIF4, JASMONATE-ZIM DOMAIN1, and BRASSINAZOLE-RESISTANT1 (BZR1)-that are key regulators in light, jasmonate, and brassinosteroid signaling pathways, respectively. 26773002 5 61 theme interactors-PHYTOCHROME-INTERACTING 848:882 arg1 PIF3 893:896 PIF3 893:896 PIF3 893:896 O-GlcNAcylation of the DELLA protein REPRESSOR OF ga1-3 (RGA) inhibits RGA binding to four of its interactors-PHYTOCHROME-INTERACTING FACTOR3 (PIF3), PIF4, JASMONATE-ZIM DOMAIN1, and BRASSINAZOLE-RESISTANT1 (BZR1)-that are key regulators in light, jasmonate, and brassinosteroid signaling pathways, respectively. 26773002 5 61 theme interactors-PHYTOCHROME-INTERACTING 848:882 arg1 PIF4 900:903 PIF4 900:903 PIF4 900:903 O-GlcNAcylation of the DELLA protein REPRESSOR OF ga1-3 (RGA) inhibits RGA binding to four of its interactors-PHYTOCHROME-INTERACTING FACTOR3 (PIF3), PIF4, JASMONATE-ZIM DOMAIN1, and BRASSINAZOLE-RESISTANT1 (BZR1)-that are key regulators in light, jasmonate, and brassinosteroid signaling pathways, respectively. 26773002 5 61 theme interactors-PHYTOCHROME-INTERACTING 848:882 arg1 FACTOR3 884:890 its interactors-PHYTOCHROME-INTERACTING FACTOR3 844:890 its interactors-PHYTOCHROME-INTERACTING FACTOR3 (PIF3) 844:897 O-GlcNAcylation of the DELLA protein REPRESSOR OF ga1-3 (RGA) inhibits RGA binding to four of its interactors-PHYTOCHROME-INTERACTING FACTOR3 (PIF3), PIF4, JASMONATE-ZIM DOMAIN1, and BRASSINAZOLE-RESISTANT1 (BZR1)-that are key regulators in light, jasmonate, and brassinosteroid signaling pathways, respectively. 26773002 6 62 theme genes 1216:1220 arg1 expression 1180:1189 decreased expression 1170:1189 decreased expression of several common target genes of DELLAs, BZR1, and PIFs 1170:1246 Consistent with this, the sec-null mutant displayed reduced responses to GA and brassinosteroid and showed decreased expression of several common target genes of DELLAs, BZR1, and PIFs. 26773002 1 63 theme transcription 139:151 arg1 regulators 153:162 transcription regulators 139:162 transcription regulators 139:162 The DELLA family of transcription regulators functions as master growth repressors in plants by inhibiting phytohormone gibberellin (GA) signaling in response to developmental and environmental cues. 26773002 2 64 theme signaling 396:404 arg1 pathways 406:413 other signaling pathways 390:413 other signaling pathways 390:413 DELLAs also play a central role in mediating cross-talk between GA and other signaling pathways via antagonistic direct interactions with key transcription factors. 26773002 5 65 theme protein 779:785 arg1 REPRESSOR 787:795 the DELLA protein REPRESSOR 769:795 the DELLA protein REPRESSOR OF ga1-3 (RGA) 769:810 O-GlcNAcylation of the DELLA protein REPRESSOR OF ga1-3 (RGA) inhibits RGA binding to four of its interactors-PHYTOCHROME-INTERACTING FACTOR3 (PIF3), PIF4, JASMONATE-ZIM DOMAIN1, and BRASSINAZOLE-RESISTANT1 (BZR1)-that are key regulators in light, jasmonate, and brassinosteroid signaling pathways, respectively. 26773002 4 66 link O-linked 657:664 arg1 O-GlcNAc 687:694 O-GlcNAc 687:694 O-GlcNAc 687:694 Here, we show that DELLAs are modified by the O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) SECRET AGENT (SEC) in Arabidopsis. 26773002 4 66 link O-linked 657:664 arg1 N-acetylglucosamine 666:684 the O-linked N-acetylglucosamine 653:684 the O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) SECRET AGENT (SEC) in Arabidopsis 653:747 Here, we show that DELLAs are modified by the O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) SECRET AGENT (SEC) in Arabidopsis. 26773002 1 67 theme regulators 153:162 arg1 family 129:134 The DELLA family 119:134 The DELLA family of transcription regulators 119:162 The DELLA family of transcription regulators functions as master growth repressors in plants by inhibiting phytohormone gibberellin (GA) signaling in response to developmental and environmental cues. 26773002 1 67 theme regulators 153:162 arg1 repressors 191:200 master growth repressors 177:200 master growth repressors in plants 177:210 The DELLA family of transcription regulators functions as master growth repressors in plants by inhibiting phytohormone gibberellin (GA) signaling in response to developmental and environmental cues. 26773002 5 68 from regulators 977:986 arg1 jasmonate 998:1006 jasmonate 998:1006 jasmonate 998:1006 O-GlcNAcylation of the DELLA protein REPRESSOR OF ga1-3 (RGA) inhibits RGA binding to four of its interactors-PHYTOCHROME-INTERACTING FACTOR3 (PIF3), PIF4, JASMONATE-ZIM DOMAIN1, and BRASSINAZOLE-RESISTANT1 (BZR1)-that are key regulators in light, jasmonate, and brassinosteroid signaling pathways, respectively. 26773002 5 68 from regulators 977:986 arg1 light 991:995 light 991:995 light 991:995 O-GlcNAcylation of the DELLA protein REPRESSOR OF ga1-3 (RGA) inhibits RGA binding to four of its interactors-PHYTOCHROME-INTERACTING FACTOR3 (PIF3), PIF4, JASMONATE-ZIM DOMAIN1, and BRASSINAZOLE-RESISTANT1 (BZR1)-that are key regulators in light, jasmonate, and brassinosteroid signaling pathways, respectively. 26773002 5 68 from regulators 977:986 arg1 pathways 1039:1046 brassinosteroid signaling pathways 1013:1046 brassinosteroid signaling pathways 1013:1046 O-GlcNAcylation of the DELLA protein REPRESSOR OF ga1-3 (RGA) inhibits RGA binding to four of its interactors-PHYTOCHROME-INTERACTING FACTOR3 (PIF3), PIF4, JASMONATE-ZIM DOMAIN1, and BRASSINAZOLE-RESISTANT1 (BZR1)-that are key regulators in light, jasmonate, and brassinosteroid signaling pathways, respectively. 26680539 3 0 with peptides 542:549 arg1 information 570:580 site-specific information 556:580 site-specific information identified by mass spectrometry (MS)-based proteomics 556:634 Due to an increasing number of O-GlcNAcylated peptides with site-specific information identified by mass spectrometry (MS)-based proteomics, we were motivated to characterize substrate site motifs of O-GlcNAc transferases. 26680539 0 1 with sites 74:78 arg1 motifs 116:121 O-GlcNAc transferase substrate motifs 85:121 O-GlcNAc transferase substrate motifs 85:121 A two-layered machine learning method to identify protein O-GlcNAcylation sites with O-GlcNAc transferase substrate motifs. 26680539 5 2 theme hidden 968:973 arg1 model 982:986 profile hidden Markov model 960:986 profile hidden Markov model (profile HMM) 960:1000 After detection of conserved motifs by using maximal dependence decomposition, profile hidden Markov model (profile HMM) was adopted to learn a first-layered model for each identified OGT substrate motif. 26680539 5 2 theme hidden 968:973 arg1 HMM 997:999 profile HMM 989:999 profile HMM 989:999 After detection of conserved motifs by using maximal dependence decomposition, profile hidden Markov model (profile HMM) was adopted to learn a first-layered model for each identified OGT substrate motif. 26680539 6 3 theme profile 1198:1204 arg1 HMMs 1206:1209 profile HMMs 1198:1209 profile HMMs 1198:1209 Support Vector Machine (SVM) was then used to generate a second-layered model learned from the output values of profile HMMs in first layer. 26680539 3 4 theme site-specific 556:568 arg1 information 570:580 site-specific information 556:580 site-specific information identified by mass spectrometry (MS)-based proteomics 556:634 Due to an increasing number of O-GlcNAcylated peptides with site-specific information identified by mass spectrometry (MS)-based proteomics, we were motivated to characterize substrate site motifs of O-GlcNAc transferases. 26680539 5 5 theme maximal 926:932 arg1 decomposition 945:957 maximal dependence decomposition 926:957 maximal dependence decomposition 926:957 After detection of conserved motifs by using maximal dependence decomposition, profile hidden Markov model (profile HMM) was adopted to learn a first-layered model for each identified OGT substrate motif. 26680539 3 6 theme mass 596:599 arg1 MS 615:616 MS 615:616 MS 615:616 Due to an increasing number of O-GlcNAcylated peptides with site-specific information identified by mass spectrometry (MS)-based proteomics, we were motivated to characterize substrate site motifs of O-GlcNAc transferases. 26680539 3 6 theme mass 596:599 arg1 spectrometry 601:612 mass spectrometry 596:612 mass spectrometry (MS)-based proteomics 596:634 Due to an increasing number of O-GlcNAcylated peptides with site-specific information identified by mass spectrometry (MS)-based proteomics, we were motivated to characterize substrate site motifs of O-GlcNAc transferases. 26680539 9 7 theme case 1689:1692 arg1 study 1694:1698 A case study 1687:1698 A case study 1687:1698 A case study indicated that the proposed method could be a feasible means of conducting preliminary analyses of protein O-GlcNAcylation and has been implemented as a web-based system, OGTSite, which is now freely available at http://csb.cse.yzu.edu.tw/OGTSite/. 26680539 9 8 from http 1913:1916 arg1 method 1728:1733 the proposed method 1715:1733 the proposed method 1715:1733 A case study indicated that the proposed method could be a feasible means of conducting preliminary analyses of protein O-GlcNAcylation and has been implemented as a web-based system, OGTSite, which is now freely available at http://csb.cse.yzu.edu.tw/OGTSite/. 26680539 9 8 from http 1913:1916 arg1 system 1863:1868 a web-based system 1851:1868 a web-based system 1851:1868 A case study indicated that the proposed method could be a feasible means of conducting preliminary analyses of protein O-GlcNAcylation and has been implemented as a web-based system, OGTSite, which is now freely available at http://csb.cse.yzu.edu.tw/OGTSite/. 26680539 9 8 from http 1913:1916 arg1 available 1900:1908 available 1900:1908 available 1900:1908 A case study indicated that the proposed method could be a feasible means of conducting preliminary analyses of protein O-GlcNAcylation and has been implemented as a web-based system, OGTSite, which is now freely available at http://csb.cse.yzu.edu.tw/OGTSite/. 26680539 5 9 theme conserved 900:908 arg1 motifs 910:915 conserved motifs 900:915 conserved motifs 900:915 After detection of conserved motifs by using maximal dependence decomposition, profile hidden Markov model (profile HMM) was adopted to learn a first-layered model for each identified OGT substrate motif. 26680539 1 10 dep serine 240:245 arg1 residues 260:267 residues 260:267 residues 260:267 Protein O-GlcNAcylation, involving the β-attachment of single N-acetylglucosamine (GlcNAc) to the hydroxyl group of serine or threonine residues, is an O-linked glycosylation catalyzed by O-GlcNAc transferase (OGT). 26680539 5 11 theme Markov 975:980 arg1 model 982:986 profile hidden Markov model 960:986 profile hidden Markov model (profile HMM) 960:1000 After detection of conserved motifs by using maximal dependence decomposition, profile hidden Markov model (profile HMM) was adopted to learn a first-layered model for each identified OGT substrate motif. 26680539 5 11 theme Markov 975:980 arg1 HMM 997:999 profile HMM 989:999 profile HMM 989:999 After detection of conserved motifs by using maximal dependence decomposition, profile hidden Markov model (profile HMM) was adopted to learn a first-layered model for each identified OGT substrate motif. 26680539 7 12 theme % 1368:1368 arg1 accuracy 1378:1385 an accuracy 1375:1385 an accuracy of 84.7% 1375:1394 The two-layered predictive model was evaluated using a five-fold cross validation which yielded a sensitivity of 85.4%, a specificity of 84.1%, and an accuracy of 84.7%. 26680539 7 12 theme % 1368:1368 arg1 sensitivity 1325:1335 a sensitivity 1323:1335 a sensitivity of 85.4% 1323:1344 The two-layered predictive model was evaluated using a five-fold cross validation which yielded a sensitivity of 85.4%, a specificity of 84.1%, and an accuracy of 84.7%. 26680539 7 12 theme % 1368:1368 arg1 specificity 1349:1359 a specificity 1347:1359 a specificity of 84.1% 1347:1368 The two-layered predictive model was evaluated using a five-fold cross validation which yielded a sensitivity of 85.4%, a specificity of 84.1%, and an accuracy of 84.7%. 26680539 8 13 from PhosphoSitePlus 1443:1457 arg1 set 1434:1436 an independent testing set 1411:1436 an independent testing set 1411:1436 Additionally, an independent testing set from PhosphoSitePlus, which was really non-homologous to the training data of predictive model, was used to demonstrate that the proposed method could provide a promising accuracy (84.05%) and outperform other O-GlcNAcylation site prediction tools. 26680539 8 13 from PhosphoSitePlus 1443:1457 arg1 non-homologous 1477:1490 non-homologous 1477:1490 non-homologous 1477:1490 Additionally, an independent testing set from PhosphoSitePlus, which was really non-homologous to the training data of predictive model, was used to demonstrate that the proposed method could provide a promising accuracy (84.05%) and outperform other O-GlcNAcylation site prediction tools. 26680539 7 14 theme predictive 1243:1252 arg1 model 1254:1258 The two-layered predictive model 1227:1258 The two-layered predictive model 1227:1258 The two-layered predictive model was evaluated using a five-fold cross validation which yielded a sensitivity of 85.4%, a specificity of 84.1%, and an accuracy of 84.7%. 26680539 1 15 theme single 179:184 arg1 GlcNAc 207:212 GlcNAc 207:212 GlcNAc 207:212 Protein O-GlcNAcylation, involving the β-attachment of single N-acetylglucosamine (GlcNAc) to the hydroxyl group of serine or threonine residues, is an O-linked glycosylation catalyzed by O-GlcNAc transferase (OGT). 26680539 1 15 theme single 179:184 arg1 N-acetylglucosamine 186:204 single N-acetylglucosamine 179:204 single N-acetylglucosamine (GlcNAc) 179:213 Protein O-GlcNAcylation, involving the β-attachment of single N-acetylglucosamine (GlcNAc) to the hydroxyl group of serine or threonine residues, is an O-linked glycosylation catalyzed by O-GlcNAc transferase (OGT). 26680539 9 16 theme feasible 1746:1753 arg1 means 1755:1759 a feasible means 1744:1759 a feasible means of conducting preliminary analyses of protein O-GlcNAcylation 1744:1821 A case study indicated that the proposed method could be a feasible means of conducting preliminary analyses of protein O-GlcNAcylation and has been implemented as a web-based system, OGTSite, which is now freely available at http://csb.cse.yzu.edu.tw/OGTSite/. 26680539 9 16 theme feasible 1746:1753 arg1 method 1728:1733 the proposed method 1715:1733 the proposed method 1715:1733 A case study indicated that the proposed method could be a feasible means of conducting preliminary analyses of protein O-GlcNAcylation and has been implemented as a web-based system, OGTSite, which is now freely available at http://csb.cse.yzu.edu.tw/OGTSite/. 26680539 8 17 theme training 1499:1506 arg1 data 1508:1511 the training data 1495:1511 the training data of predictive model 1495:1531 Additionally, an independent testing set from PhosphoSitePlus, which was really non-homologous to the training data of predictive model, was used to demonstrate that the proposed method could provide a promising accuracy (84.05%) and outperform other O-GlcNAcylation site prediction tools. 26680539 4 18 theme sites 813:817 arg1 dataset 758:764 a non-redundant dataset 742:764 a non-redundant dataset of 410 experimentally verified O-GlcNAcylation sites 742:817 In this investigation, a non-redundant dataset of 410 experimentally verified O-GlcNAcylation sites were manually extracted from dbOGAP, OGlycBase and UniProtKB. 26680539 0 19 theme transferase 94:104 arg1 motifs 116:121 O-GlcNAc transferase substrate motifs 85:121 O-GlcNAc transferase substrate motifs 85:121 A two-layered machine learning method to identify protein O-GlcNAcylation sites with O-GlcNAc transferase substrate motifs. 26680539 2 20 theme substrate 393:401 arg1 specificity 403:413 OGT's substrate specificity 387:413 OGT's substrate specificity 387:413 Molecular level investigation of the basis for OGT's substrate specificity should aid understanding how O-GlcNAc contributes to diverse cellular processes. 26680539 9 21 theme preliminary 1775:1785 arg1 analyses 1787:1794 preliminary analyses 1775:1794 preliminary analyses of protein O-GlcNAcylation 1775:1821 A case study indicated that the proposed method could be a feasible means of conducting preliminary analyses of protein O-GlcNAcylation and has been implemented as a web-based system, OGTSite, which is now freely available at http://csb.cse.yzu.edu.tw/OGTSite/. 26680539 8 22 theme model 1527:1531 arg1 data 1508:1511 the training data 1495:1511 the training data of predictive model 1495:1531 Additionally, an independent testing set from PhosphoSitePlus, which was really non-homologous to the training data of predictive model, was used to demonstrate that the proposed method could provide a promising accuracy (84.05%) and outperform other O-GlcNAcylation site prediction tools. 26680539 1 23 theme O-linked 276:283 arg1 glycosylation 285:297 an O-linked glycosylation 273:297 an O-linked glycosylation catalyzed by O-GlcNAc transferase (OGT) 273:337 Protein O-GlcNAcylation, involving the β-attachment of single N-acetylglucosamine (GlcNAc) to the hydroxyl group of serine or threonine residues, is an O-linked glycosylation catalyzed by O-GlcNAc transferase (OGT). 26680539 1 23 theme O-linked 276:283 arg1 O-GlcNAcylation 132:146 Protein O-GlcNAcylation 124:146 Protein O-GlcNAcylation 124:146 Protein O-GlcNAcylation, involving the β-attachment of single N-acetylglucosamine (GlcNAc) to the hydroxyl group of serine or threonine residues, is an O-linked glycosylation catalyzed by O-GlcNAc transferase (OGT). 26680539 4 24 theme verified 788:795 arg1 sites 813:817 410 experimentally verified O-GlcNAcylation sites 769:817 410 experimentally verified O-GlcNAcylation sites 769:817 In this investigation, a non-redundant dataset of 410 experimentally verified O-GlcNAcylation sites were manually extracted from dbOGAP, OGlycBase and UniProtKB. 26680539 0 25 theme machine 14:20 arg1 method 31:36 A two-layered machine learning method 0:36 A two-layered machine learning method 0:36 A two-layered machine learning method to identify protein O-GlcNAcylation sites with O-GlcNAc transferase substrate motifs. 26680539 6 26 theme Vector 1094:1099 arg1 SVM 1110:1112 SVM 1110:1112 SVM 1110:1112 Support Vector Machine (SVM) was then used to generate a second-layered model learned from the output values of profile HMMs in first layer. 26680539 6 26 theme Vector 1094:1099 arg1 Machine 1101:1107 Support Vector Machine 1086:1107 Support Vector Machine (SVM) 1086:1113 Support Vector Machine (SVM) was then used to generate a second-layered model learned from the output values of profile HMMs in first layer. 26680539 9 27 theme O-GlcNAcylation 1807:1821 arg1 analyses 1787:1794 preliminary analyses 1775:1794 preliminary analyses of protein O-GlcNAcylation 1775:1821 A case study indicated that the proposed method could be a feasible means of conducting preliminary analyses of protein O-GlcNAcylation and has been implemented as a web-based system, OGTSite, which is now freely available at http://csb.cse.yzu.edu.tw/OGTSite/. 26680539 0 28 theme O-GlcNAcylation 58:72 arg1 sites 74:78 protein O-GlcNAcylation sites 50:78 protein O-GlcNAcylation sites with O-GlcNAc transferase substrate motifs 50:121 A two-layered machine learning method to identify protein O-GlcNAcylation sites with O-GlcNAc transferase substrate motifs. 26680539 3 29 theme site 681:684 arg1 motifs 686:691 substrate site motifs 671:691 substrate site motifs of O-GlcNAc transferases 671:716 Due to an increasing number of O-GlcNAcylated peptides with site-specific information identified by mass spectrometry (MS)-based proteomics, we were motivated to characterize substrate site motifs of O-GlcNAc transferases. 26680539 1 30 theme N-acetylglucosamine 186:204 arg1 β-attachment 163:174 the β-attachment 159:174 the β-attachment of single N-acetylglucosamine (GlcNAc) to the hydroxyl group of serine or threonine residues 159:267 Protein O-GlcNAcylation, involving the β-attachment of single N-acetylglucosamine (GlcNAc) to the hydroxyl group of serine or threonine residues, is an O-linked glycosylation catalyzed by O-GlcNAc transferase (OGT). 26680539 1 31 theme O-GlcNAc 312:319 arg1 transferase 321:331 O-GlcNAc transferase 312:331 O-GlcNAc transferase (OGT) 312:337 Protein O-GlcNAcylation, involving the β-attachment of single N-acetylglucosamine (GlcNAc) to the hydroxyl group of serine or threonine residues, is an O-linked glycosylation catalyzed by O-GlcNAc transferase (OGT). 26680539 1 31 theme O-GlcNAc 312:319 arg1 OGT 334:336 OGT 334:336 OGT 334:336 Protein O-GlcNAcylation, involving the β-attachment of single N-acetylglucosamine (GlcNAc) to the hydroxyl group of serine or threonine residues, is an O-linked glycosylation catalyzed by O-GlcNAc transferase (OGT). 26680539 5 32 theme OGT 1065:1067 arg1 motif 1079:1083 each identified OGT substrate motif 1049:1083 each identified OGT substrate motif 1049:1083 After detection of conserved motifs by using maximal dependence decomposition, profile hidden Markov model (profile HMM) was adopted to learn a first-layered model for each identified OGT substrate motif. 26680539 2 33 theme cellular 476:483 arg1 processes 485:493 diverse cellular processes 468:493 diverse cellular processes 468:493 Molecular level investigation of the basis for OGT's substrate specificity should aid understanding how O-GlcNAc contributes to diverse cellular processes. 26680539 8 34 used used 1538:1541 arg2 non-homologous 1477:1490 non-homologous 1477:1490 non-homologous 1477:1490 Additionally, an independent testing set from PhosphoSitePlus, which was really non-homologous to the training data of predictive model, was used to demonstrate that the proposed method could provide a promising accuracy (84.05%) and outperform other O-GlcNAcylation site prediction tools. 26680539 8 34 used used 1538:1541 arg2 set 1434:1436 an independent testing set 1411:1436 an independent testing set 1411:1436 Additionally, an independent testing set from PhosphoSitePlus, which was really non-homologous to the training data of predictive model, was used to demonstrate that the proposed method could provide a promising accuracy (84.05%) and outperform other O-GlcNAcylation site prediction tools. 26680539 2 35 theme level 350:354 arg1 investigation 356:368 Molecular level investigation 340:368 Molecular level investigation of the basis for OGT's substrate specificity 340:413 Molecular level investigation of the basis for OGT's substrate specificity should aid understanding how O-GlcNAc contributes to diverse cellular processes. 26680539 8 36 theme proposed 1567:1574 arg1 method 1576:1581 the proposed method 1563:1581 the proposed method 1563:1581 Additionally, an independent testing set from PhosphoSitePlus, which was really non-homologous to the training data of predictive model, was used to demonstrate that the proposed method could provide a promising accuracy (84.05%) and outperform other O-GlcNAcylation site prediction tools. 26680539 3 37 theme transferases 705:716 arg1 motifs 686:691 substrate site motifs 671:691 substrate site motifs of O-GlcNAc transferases 671:716 Due to an increasing number of O-GlcNAcylated peptides with site-specific information identified by mass spectrometry (MS)-based proteomics, we were motivated to characterize substrate site motifs of O-GlcNAc transferases. 26680539 8 38 theme testing 1426:1432 arg1 set 1434:1436 an independent testing set 1411:1436 an independent testing set 1411:1436 Additionally, an independent testing set from PhosphoSitePlus, which was really non-homologous to the training data of predictive model, was used to demonstrate that the proposed method could provide a promising accuracy (84.05%) and outperform other O-GlcNAcylation site prediction tools. 26680539 8 38 theme testing 1426:1432 arg1 non-homologous 1477:1490 non-homologous 1477:1490 non-homologous 1477:1490 Additionally, an independent testing set from PhosphoSitePlus, which was really non-homologous to the training data of predictive model, was used to demonstrate that the proposed method could provide a promising accuracy (84.05%) and outperform other O-GlcNAcylation site prediction tools. 26680539 3 39 theme O-GlcNAcylated 527:540 arg1 peptides 542:549 O-GlcNAcylated peptides 527:549 O-GlcNAcylated peptides with site-specific information identified by mass spectrometry (MS)-based proteomics 527:634 Due to an increasing number of O-GlcNAcylated peptides with site-specific information identified by mass spectrometry (MS)-based proteomics, we were motivated to characterize substrate site motifs of O-GlcNAc transferases. 26680539 7 40 theme five-fold 1282:1290 arg1 validation 1298:1307 a five-fold cross validation 1280:1307 a five-fold cross validation which yielded a sensitivity of 85.4%, a specificity of 84.1%, and an accuracy of 84.7% 1280:1394 The two-layered predictive model was evaluated using a five-fold cross validation which yielded a sensitivity of 85.4%, a specificity of 84.1%, and an accuracy of 84.7%. 26680539 7 41 theme two-layered 1231:1241 arg1 model 1254:1258 The two-layered predictive model 1227:1258 The two-layered predictive model 1227:1258 The two-layered predictive model was evaluated using a five-fold cross validation which yielded a sensitivity of 85.4%, a specificity of 84.1%, and an accuracy of 84.7%. 26680539 8 42 theme O-GlcNAcylation 1648:1662 arg1 tools 1680:1684 other O-GlcNAcylation site prediction tools 1642:1684 other O-GlcNAcylation site prediction tools 1642:1684 Additionally, an independent testing set from PhosphoSitePlus, which was really non-homologous to the training data of predictive model, was used to demonstrate that the proposed method could provide a promising accuracy (84.05%) and outperform other O-GlcNAcylation site prediction tools. 26680539 8 43 theme prediction 1669:1678 arg1 tools 1680:1684 other O-GlcNAcylation site prediction tools 1642:1684 other O-GlcNAcylation site prediction tools 1642:1684 Additionally, an independent testing set from PhosphoSitePlus, which was really non-homologous to the training data of predictive model, was used to demonstrate that the proposed method could provide a promising accuracy (84.05%) and outperform other O-GlcNAcylation site prediction tools. 26680539 6 44 theme HMMs 1206:1209 arg1 values 1188:1193 the output values 1177:1193 the output values of profile HMMs in first layer 1177:1224 Support Vector Machine (SVM) was then used to generate a second-layered model learned from the output values of profile HMMs in first layer. 26680539 5 45 theme motifs 910:915 arg1 detection 887:895 detection 887:895 detection of conserved motifs by using maximal dependence decomposition 887:957 After detection of conserved motifs by using maximal dependence decomposition, profile hidden Markov model (profile HMM) was adopted to learn a first-layered model for each identified OGT substrate motif. 26680539 3 46 theme spectrometry 601:612 arg1 proteomics 625:634 mass spectrometry (MS)-based proteomics 596:634 mass spectrometry (MS)-based proteomics 596:634 Due to an increasing number of O-GlcNAcylated peptides with site-specific information identified by mass spectrometry (MS)-based proteomics, we were motivated to characterize substrate site motifs of O-GlcNAc transferases. 26680539 6 47 theme output 1181:1186 arg1 values 1188:1193 the output values 1177:1193 the output values of profile HMMs in first layer 1177:1224 Support Vector Machine (SVM) was then used to generate a second-layered model learned from the output values of profile HMMs in first layer. 26680539 5 48 theme profile 960:966 arg1 model 982:986 profile hidden Markov model 960:986 profile hidden Markov model (profile HMM) 960:1000 After detection of conserved motifs by using maximal dependence decomposition, profile hidden Markov model (profile HMM) was adopted to learn a first-layered model for each identified OGT substrate motif. 26680539 5 48 theme profile 960:966 arg1 HMM 997:999 profile HMM 989:999 profile HMM 989:999 After detection of conserved motifs by using maximal dependence decomposition, profile hidden Markov model (profile HMM) was adopted to learn a first-layered model for each identified OGT substrate motif. 26680539 2 49 theme Molecular 340:348 arg1 investigation 356:368 Molecular level investigation 340:368 Molecular level investigation of the basis for OGT's substrate specificity 340:413 Molecular level investigation of the basis for OGT's substrate specificity should aid understanding how O-GlcNAc contributes to diverse cellular processes. 26680539 3 50 theme -based 618:623 arg1 proteomics 625:634 mass spectrometry (MS)-based proteomics 596:634 mass spectrometry (MS)-based proteomics 596:634 Due to an increasing number of O-GlcNAcylated peptides with site-specific information identified by mass spectrometry (MS)-based proteomics, we were motivated to characterize substrate site motifs of O-GlcNAc transferases. 26680539 1 51 theme hydroxyl 222:229 arg1 threonine 250:258 threonine 250:258 threonine 250:258 Protein O-GlcNAcylation, involving the β-attachment of single N-acetylglucosamine (GlcNAc) to the hydroxyl group of serine or threonine residues, is an O-linked glycosylation catalyzed by O-GlcNAc transferase (OGT). 26680539 1 51 theme hydroxyl 222:229 arg1 serine 240:245 serine 240:245 serine 240:245 Protein O-GlcNAcylation, involving the β-attachment of single N-acetylglucosamine (GlcNAc) to the hydroxyl group of serine or threonine residues, is an O-linked glycosylation catalyzed by O-GlcNAc transferase (OGT). 26680539 1 51 theme hydroxyl 222:229 arg1 group 231:235 the hydroxyl group 218:235 the hydroxyl group of serine or threonine residues 218:267 Protein O-GlcNAcylation, involving the β-attachment of single N-acetylglucosamine (GlcNAc) to the hydroxyl group of serine or threonine residues, is an O-linked glycosylation catalyzed by O-GlcNAc transferase (OGT). 26680539 6 52 used used 1124:1127 arg2 SVM 1110:1112 SVM 1110:1112 SVM 1110:1112 Support Vector Machine (SVM) was then used to generate a second-layered model learned from the output values of profile HMMs in first layer. 26680539 6 52 used used 1124:1127 arg2 Machine 1101:1107 Support Vector Machine 1086:1107 Support Vector Machine (SVM) 1086:1113 Support Vector Machine (SVM) was then used to generate a second-layered model learned from the output values of profile HMMs in first layer. 26680539 1 53 theme Protein 124:130 arg1 O-GlcNAcylation 132:146 Protein O-GlcNAcylation 124:146 Protein O-GlcNAcylation 124:146 Protein O-GlcNAcylation, involving the β-attachment of single N-acetylglucosamine (GlcNAc) to the hydroxyl group of serine or threonine residues, is an O-linked glycosylation catalyzed by O-GlcNAc transferase (OGT). 26680539 1 53 theme Protein 124:130 arg1 glycosylation 285:297 an O-linked glycosylation 273:297 an O-linked glycosylation catalyzed by O-GlcNAc transferase (OGT) 273:337 Protein O-GlcNAcylation, involving the β-attachment of single N-acetylglucosamine (GlcNAc) to the hydroxyl group of serine or threonine residues, is an O-linked glycosylation catalyzed by O-GlcNAc transferase (OGT). 26680539 9 54 theme proposed 1719:1726 arg1 means 1755:1759 a feasible means 1744:1759 a feasible means of conducting preliminary analyses of protein O-GlcNAcylation 1744:1821 A case study indicated that the proposed method could be a feasible means of conducting preliminary analyses of protein O-GlcNAcylation and has been implemented as a web-based system, OGTSite, which is now freely available at http://csb.cse.yzu.edu.tw/OGTSite/. 26680539 9 54 theme proposed 1719:1726 arg1 method 1728:1733 the proposed method 1715:1733 the proposed method 1715:1733 A case study indicated that the proposed method could be a feasible means of conducting preliminary analyses of protein O-GlcNAcylation and has been implemented as a web-based system, OGTSite, which is now freely available at http://csb.cse.yzu.edu.tw/OGTSite/. 26680539 9 54 theme proposed 1719:1726 arg1 available 1900:1908 available 1900:1908 available 1900:1908 A case study indicated that the proposed method could be a feasible means of conducting preliminary analyses of protein O-GlcNAcylation and has been implemented as a web-based system, OGTSite, which is now freely available at http://csb.cse.yzu.edu.tw/OGTSite/. 26680539 9 54 theme proposed 1719:1726 arg1 system 1863:1868 a web-based system 1851:1868 a web-based system 1851:1868 A case study indicated that the proposed method could be a feasible means of conducting preliminary analyses of protein O-GlcNAcylation and has been implemented as a web-based system, OGTSite, which is now freely available at http://csb.cse.yzu.edu.tw/OGTSite/. 26680539 4 55 theme non-redundant 744:756 arg1 dataset 758:764 a non-redundant dataset 742:764 a non-redundant dataset of 410 experimentally verified O-GlcNAcylation sites 742:817 In this investigation, a non-redundant dataset of 410 experimentally verified O-GlcNAcylation sites were manually extracted from dbOGAP, OGlycBase and UniProtKB. 26680539 6 56 theme second-layered 1143:1156 arg1 model 1158:1162 a second-layered model 1141:1162 a second-layered model learned from the output values of profile HMMs in first layer 1141:1224 Support Vector Machine (SVM) was then used to generate a second-layered model learned from the output values of profile HMMs in first layer. 26680539 5 57 theme dependence 934:943 arg1 decomposition 945:957 maximal dependence decomposition 926:957 maximal dependence decomposition 926:957 After detection of conserved motifs by using maximal dependence decomposition, profile hidden Markov model (profile HMM) was adopted to learn a first-layered model for each identified OGT substrate motif. 26680539 6 58 theme first 1214:1218 arg1 layer 1220:1224 first layer 1214:1224 first layer 1214:1224 Support Vector Machine (SVM) was then used to generate a second-layered model learned from the output values of profile HMMs in first layer. 26680539 0 59 theme O-GlcNAc 85:92 arg1 transferase 94:104 O-GlcNAc transferase 85:104 O-GlcNAc transferase substrate motifs 85:121 A two-layered machine learning method to identify protein O-GlcNAcylation sites with O-GlcNAc transferase substrate motifs. 26680539 0 60 theme substrate 106:114 arg1 motifs 116:121 O-GlcNAc transferase substrate motifs 85:121 O-GlcNAc transferase substrate motifs 85:121 A two-layered machine learning method to identify protein O-GlcNAcylation sites with O-GlcNAc transferase substrate motifs. 26680539 7 61 theme % 1394:1394 arg1 accuracy 1378:1385 an accuracy 1375:1385 an accuracy of 84.7% 1375:1394 The two-layered predictive model was evaluated using a five-fold cross validation which yielded a sensitivity of 85.4%, a specificity of 84.1%, and an accuracy of 84.7%. 26680539 7 61 theme % 1394:1394 arg1 sensitivity 1325:1335 a sensitivity 1323:1335 a sensitivity of 85.4% 1323:1344 The two-layered predictive model was evaluated using a five-fold cross validation which yielded a sensitivity of 85.4%, a specificity of 84.1%, and an accuracy of 84.7%. 26680539 7 61 theme % 1394:1394 arg1 specificity 1349:1359 a specificity 1347:1359 a specificity of 84.1% 1347:1368 The two-layered predictive model was evaluated using a five-fold cross validation which yielded a sensitivity of 85.4%, a specificity of 84.1%, and an accuracy of 84.7%. 26680539 8 62 theme predictive 1516:1525 arg1 model 1527:1531 predictive model 1516:1531 predictive model 1516:1531 Additionally, an independent testing set from PhosphoSitePlus, which was really non-homologous to the training data of predictive model, was used to demonstrate that the proposed method could provide a promising accuracy (84.05%) and outperform other O-GlcNAcylation site prediction tools. 26680539 4 63 theme O-GlcNAcylation 797:811 arg1 sites 813:817 410 experimentally verified O-GlcNAcylation sites 769:817 410 experimentally verified O-GlcNAcylation sites 769:817 In this investigation, a non-redundant dataset of 410 experimentally verified O-GlcNAcylation sites were manually extracted from dbOGAP, OGlycBase and UniProtKB. 26680539 0 64 theme two-layered 2:12 arg1 method 31:36 A two-layered machine learning method 0:36 A two-layered machine learning method 0:36 A two-layered machine learning method to identify protein O-GlcNAcylation sites with O-GlcNAc transferase substrate motifs. 26680539 5 65 theme profile 989:995 arg1 model 982:986 profile hidden Markov model 960:986 profile hidden Markov model (profile HMM) 960:1000 After detection of conserved motifs by using maximal dependence decomposition, profile hidden Markov model (profile HMM) was adopted to learn a first-layered model for each identified OGT substrate motif. 26680539 5 65 theme profile 989:995 arg1 HMM 997:999 profile HMM 989:999 profile HMM 989:999 After detection of conserved motifs by using maximal dependence decomposition, profile hidden Markov model (profile HMM) was adopted to learn a first-layered model for each identified OGT substrate motif. 26680539 7 66 theme % 1344:1344 arg1 accuracy 1378:1385 an accuracy 1375:1385 an accuracy of 84.7% 1375:1394 The two-layered predictive model was evaluated using a five-fold cross validation which yielded a sensitivity of 85.4%, a specificity of 84.1%, and an accuracy of 84.7%. 26680539 7 66 theme % 1344:1344 arg1 sensitivity 1325:1335 a sensitivity 1323:1335 a sensitivity of 85.4% 1323:1344 The two-layered predictive model was evaluated using a five-fold cross validation which yielded a sensitivity of 85.4%, a specificity of 84.1%, and an accuracy of 84.7%. 26680539 7 66 theme % 1344:1344 arg1 specificity 1349:1359 a specificity 1347:1359 a specificity of 84.1% 1347:1368 The two-layered predictive model was evaluated using a five-fold cross validation which yielded a sensitivity of 85.4%, a specificity of 84.1%, and an accuracy of 84.7%. 26680539 0 67 theme learning 22:29 arg1 method 31:36 A two-layered machine learning method 0:36 A two-layered machine learning method 0:36 A two-layered machine learning method to identify protein O-GlcNAcylation sites with O-GlcNAc transferase substrate motifs. 26680539 9 68 theme protein 1799:1805 arg1 O-GlcNAcylation 1807:1821 protein O-GlcNAcylation 1799:1821 protein O-GlcNAcylation 1799:1821 A case study indicated that the proposed method could be a feasible means of conducting preliminary analyses of protein O-GlcNAcylation and has been implemented as a web-based system, OGTSite, which is now freely available at http://csb.cse.yzu.edu.tw/OGTSite/. 26680539 3 69 theme substrate 671:679 arg1 motifs 686:691 substrate site motifs 671:691 substrate site motifs of O-GlcNAc transferases 671:716 Due to an increasing number of O-GlcNAcylated peptides with site-specific information identified by mass spectrometry (MS)-based proteomics, we were motivated to characterize substrate site motifs of O-GlcNAc transferases. 26680539 6 70 from values 1188:1193 arg1 layer 1220:1224 first layer 1214:1224 first layer 1214:1224 Support Vector Machine (SVM) was then used to generate a second-layered model learned from the output values of profile HMMs in first layer. 26680539 2 71 theme basis 377:381 arg1 investigation 356:368 Molecular level investigation 340:368 Molecular level investigation of the basis for OGT's substrate specificity 340:413 Molecular level investigation of the basis for OGT's substrate specificity should aid understanding how O-GlcNAc contributes to diverse cellular processes. 26680539 5 72 theme identified 1054:1063 arg1 motif 1079:1083 each identified OGT substrate motif 1049:1083 each identified OGT substrate motif 1049:1083 After detection of conserved motifs by using maximal dependence decomposition, profile hidden Markov model (profile HMM) was adopted to learn a first-layered model for each identified OGT substrate motif. 26680539 6 73 theme Support 1086:1092 arg1 SVM 1110:1112 SVM 1110:1112 SVM 1110:1112 Support Vector Machine (SVM) was then used to generate a second-layered model learned from the output values of profile HMMs in first layer. 26680539 6 73 theme Support 1086:1092 arg1 Machine 1101:1107 Support Vector Machine 1086:1107 Support Vector Machine (SVM) 1086:1113 Support Vector Machine (SVM) was then used to generate a second-layered model learned from the output values of profile HMMs in first layer. 26680539 0 74 theme protein 50:56 arg1 sites 74:78 protein O-GlcNAcylation sites 50:78 protein O-GlcNAcylation sites with O-GlcNAc transferase substrate motifs 50:121 A two-layered machine learning method to identify protein O-GlcNAcylation sites with O-GlcNAc transferase substrate motifs. 26680539 5 75 theme substrate 1069:1077 arg1 motif 1079:1083 each identified OGT substrate motif 1049:1083 each identified OGT substrate motif 1049:1083 After detection of conserved motifs by using maximal dependence decomposition, profile hidden Markov model (profile HMM) was adopted to learn a first-layered model for each identified OGT substrate motif. 26680539 2 76 theme diverse 468:474 arg1 processes 485:493 diverse cellular processes 468:493 diverse cellular processes 468:493 Molecular level investigation of the basis for OGT's substrate specificity should aid understanding how O-GlcNAc contributes to diverse cellular processes. 26680539 3 77 theme O-GlcNAc 696:703 arg1 transferases 705:716 O-GlcNAc transferases 696:716 O-GlcNAc transferases 696:716 Due to an increasing number of O-GlcNAcylated peptides with site-specific information identified by mass spectrometry (MS)-based proteomics, we were motivated to characterize substrate site motifs of O-GlcNAc transferases. 26680539 2 78 dep aid 422:424 arg1 contributes 453:463 contributes 453:463 contributes to diverse cellular processes 453:493 Molecular level investigation of the basis for OGT's substrate specificity should aid understanding how O-GlcNAc contributes to diverse cellular processes. 26680539 3 79 theme increasing 506:515 arg1 number 517:522 an increasing number 503:522 an increasing number of O-GlcNAcylated peptides with site-specific information identified by mass spectrometry (MS)-based proteomics 503:634 Due to an increasing number of O-GlcNAcylated peptides with site-specific information identified by mass spectrometry (MS)-based proteomics, we were motivated to characterize substrate site motifs of O-GlcNAc transferases. 26680539 5 80 theme first-layered 1025:1037 arg1 model 1039:1043 a first-layered model 1023:1043 a first-layered model for each identified OGT substrate motif 1023:1083 After detection of conserved motifs by using maximal dependence decomposition, profile hidden Markov model (profile HMM) was adopted to learn a first-layered model for each identified OGT substrate motif. 26680539 7 81 theme cross 1292:1296 arg1 validation 1298:1307 a five-fold cross validation 1280:1307 a five-fold cross validation which yielded a sensitivity of 85.4%, a specificity of 84.1%, and an accuracy of 84.7% 1280:1394 The two-layered predictive model was evaluated using a five-fold cross validation which yielded a sensitivity of 85.4%, a specificity of 84.1%, and an accuracy of 84.7%. 26680539 8 82 theme other 1642:1646 arg1 tools 1680:1684 other O-GlcNAcylation site prediction tools 1642:1684 other O-GlcNAcylation site prediction tools 1642:1684 Additionally, an independent testing set from PhosphoSitePlus, which was really non-homologous to the training data of predictive model, was used to demonstrate that the proposed method could provide a promising accuracy (84.05%) and outperform other O-GlcNAcylation site prediction tools. 26680539 1 83 theme serine 240:245 arg1 threonine 250:258 threonine 250:258 threonine 250:258 Protein O-GlcNAcylation, involving the β-attachment of single N-acetylglucosamine (GlcNAc) to the hydroxyl group of serine or threonine residues, is an O-linked glycosylation catalyzed by O-GlcNAc transferase (OGT). 26680539 1 83 theme serine 240:245 arg1 serine 240:245 serine 240:245 serine 240:245 Protein O-GlcNAcylation, involving the β-attachment of single N-acetylglucosamine (GlcNAc) to the hydroxyl group of serine or threonine residues, is an O-linked glycosylation catalyzed by O-GlcNAc transferase (OGT). 26680539 1 83 theme serine 240:245 arg1 group 231:235 the hydroxyl group 218:235 the hydroxyl group of serine or threonine residues 218:267 Protein O-GlcNAcylation, involving the β-attachment of single N-acetylglucosamine (GlcNAc) to the hydroxyl group of serine or threonine residues, is an O-linked glycosylation catalyzed by O-GlcNAc transferase (OGT). 26680539 9 84 theme web-based 1853:1861 arg1 method 1728:1733 the proposed method 1715:1733 the proposed method 1715:1733 A case study indicated that the proposed method could be a feasible means of conducting preliminary analyses of protein O-GlcNAcylation and has been implemented as a web-based system, OGTSite, which is now freely available at http://csb.cse.yzu.edu.tw/OGTSite/. 26680539 9 84 theme web-based 1853:1861 arg1 OGTSite 1871:1877 OGTSite 1871:1877 OGTSite 1871:1877 A case study indicated that the proposed method could be a feasible means of conducting preliminary analyses of protein O-GlcNAcylation and has been implemented as a web-based system, OGTSite, which is now freely available at http://csb.cse.yzu.edu.tw/OGTSite/. 26680539 9 84 theme web-based 1853:1861 arg1 available 1900:1908 available 1900:1908 available 1900:1908 A case study indicated that the proposed method could be a feasible means of conducting preliminary analyses of protein O-GlcNAcylation and has been implemented as a web-based system, OGTSite, which is now freely available at http://csb.cse.yzu.edu.tw/OGTSite/. 26680539 9 84 theme web-based 1853:1861 arg1 system 1863:1868 a web-based system 1851:1868 a web-based system 1851:1868 A case study indicated that the proposed method could be a feasible means of conducting preliminary analyses of protein O-GlcNAcylation and has been implemented as a web-based system, OGTSite, which is now freely available at http://csb.cse.yzu.edu.tw/OGTSite/. 26680539 8 85 theme promising 1599:1607 arg1 accuracy 1609:1616 a promising accuracy 1597:1616 a promising accuracy (84.05%) 1597:1625 Additionally, an independent testing set from PhosphoSitePlus, which was really non-homologous to the training data of predictive model, was used to demonstrate that the proposed method could provide a promising accuracy (84.05%) and outperform other O-GlcNAcylation site prediction tools. 26680539 8 85 theme promising 1599:1607 arg1 % 1624:1624 84.05% 1619:1624 84.05% 1619:1624 Additionally, an independent testing set from PhosphoSitePlus, which was really non-homologous to the training data of predictive model, was used to demonstrate that the proposed method could provide a promising accuracy (84.05%) and outperform other O-GlcNAcylation site prediction tools. 26680539 8 86 theme independent 1414:1424 arg1 set 1434:1436 an independent testing set 1411:1436 an independent testing set 1411:1436 Additionally, an independent testing set from PhosphoSitePlus, which was really non-homologous to the training data of predictive model, was used to demonstrate that the proposed method could provide a promising accuracy (84.05%) and outperform other O-GlcNAcylation site prediction tools. 26680539 8 86 theme independent 1414:1424 arg1 non-homologous 1477:1490 non-homologous 1477:1490 non-homologous 1477:1490 Additionally, an independent testing set from PhosphoSitePlus, which was really non-homologous to the training data of predictive model, was used to demonstrate that the proposed method could provide a promising accuracy (84.05%) and outperform other O-GlcNAcylation site prediction tools. 26680539 1 87 link O-linked 276:283 arg1 glycosylation 285:297 an O-linked glycosylation 273:297 an O-linked glycosylation catalyzed by O-GlcNAc transferase (OGT) 273:337 Protein O-GlcNAcylation, involving the β-attachment of single N-acetylglucosamine (GlcNAc) to the hydroxyl group of serine or threonine residues, is an O-linked glycosylation catalyzed by O-GlcNAc transferase (OGT). 26680539 1 87 link O-linked 276:283 arg1 O-GlcNAcylation 132:146 Protein O-GlcNAcylation 124:146 Protein O-GlcNAcylation 124:146 Protein O-GlcNAcylation, involving the β-attachment of single N-acetylglucosamine (GlcNAc) to the hydroxyl group of serine or threonine residues, is an O-linked glycosylation catalyzed by O-GlcNAc transferase (OGT). 26680539 3 88 theme peptides 542:549 arg1 number 517:522 an increasing number 503:522 an increasing number of O-GlcNAcylated peptides with site-specific information identified by mass spectrometry (MS)-based proteomics 503:634 Due to an increasing number of O-GlcNAcylated peptides with site-specific information identified by mass spectrometry (MS)-based proteomics, we were motivated to characterize substrate site motifs of O-GlcNAc transferases. 26680539 8 89 theme site 1664:1667 arg1 tools 1680:1684 other O-GlcNAcylation site prediction tools 1642:1684 other O-GlcNAcylation site prediction tools 1642:1684 Additionally, an independent testing set from PhosphoSitePlus, which was really non-homologous to the training data of predictive model, was used to demonstrate that the proposed method could provide a promising accuracy (84.05%) and outperform other O-GlcNAcylation site prediction tools. 26680539 1 90 theme threonine 250:258 arg1 threonine 250:258 threonine 250:258 threonine 250:258 Protein O-GlcNAcylation, involving the β-attachment of single N-acetylglucosamine (GlcNAc) to the hydroxyl group of serine or threonine residues, is an O-linked glycosylation catalyzed by O-GlcNAc transferase (OGT). 26680539 1 90 theme threonine 250:258 arg1 serine 240:245 serine 240:245 serine 240:245 Protein O-GlcNAcylation, involving the β-attachment of single N-acetylglucosamine (GlcNAc) to the hydroxyl group of serine or threonine residues, is an O-linked glycosylation catalyzed by O-GlcNAc transferase (OGT). 26680539 1 90 theme threonine 250:258 arg1 group 231:235 the hydroxyl group 218:235 the hydroxyl group of serine or threonine residues 218:267 Protein O-GlcNAcylation, involving the β-attachment of single N-acetylglucosamine (GlcNAc) to the hydroxyl group of serine or threonine residues, is an O-linked glycosylation catalyzed by O-GlcNAc transferase (OGT). 25256514 5 0 theme minor 733:737 arg1 β-L-Araf- 748:756 minor terminal β-L-Araf- 733:756 minor terminal β-L-Araf-(1 →... 733:763 Although most L-Araf were in α-anomeric form, minor terminal β-L-Araf-(1 →... was detected. 25256514 9 1 theme roots 1124:1128 arg1 effect 1066:1071 a strongest stimulating effect 1042:1071 a strongest stimulating effect on germination and growth rate of seeds, germs and roots of Triticum aestivum, Avena sativa, and Secale cereale 1042:1183 Galacturonan had a strongest stimulating effect on germination and growth rate of seeds, germs and roots of Triticum aestivum, Avena sativa, and Secale cereale. 25256514 3 2 theme rhamnose 457:464 arg1 branching 466:474 rhamnose branching 457:474 rhamnose branching 457:474 The macromolecule backbone was represented mainly by RG-I (molar ratio GalA:Rha ∼ 1.3:1) patterns with high degree of rhamnose branching. 25256514 6 3 theme minor 845:849 arg1 AG-I 851:854 minor AG-I 845:854 minor AG-I 845:854 1,4-β-D-linked Galp residues found in the side chains account for minor AG-I or 1,4-galactan, as compared to arabinan. 25256514 1 4 theme Abies 248:252 arg1 L 263:263 Abies sibirica L 248:263 Abies sibirica L 248:263 Highly branched arabinan-rich pectic polysaccharides, containing 84% of arabinose, was extracted from wood greenery of Abies sibirica L. 25256514 0 5 theme Biological 82:91 arg1 activity 93:100 L. Biological activity 79:100 L. Biological activity of pectins of A. sibirica 79:126 Structural studies of arabinan-rich pectic polysaccharides from Abies sibirica L. Biological activity of pectins of A. sibirica. 25256514 0 6 from studies 11:17 arg1 Abies 64:68 Abies 64:68 Abies 64:68 Structural studies of arabinan-rich pectic polysaccharides from Abies sibirica L. Biological activity of pectins of A. sibirica. 25256514 7 7 theme tentative 900:908 arg1 structure 910:918 A tentative structure 898:918 A tentative structure 898:918 A tentative structure was proposed. 25256514 3 8 theme branching 466:474 arg1 degree 447:452 high degree 442:452 high degree of rhamnose branching 442:474 The macromolecule backbone was represented mainly by RG-I (molar ratio GalA:Rha ∼ 1.3:1) patterns with high degree of rhamnose branching. 25256514 9 9 dep Avena 1152:1156 arg1 sativa 1158:1163 Avena sativa 1152:1163 Avena sativa 1152:1163 Galacturonan had a strongest stimulating effect on germination and growth rate of seeds, germs and roots of Triticum aestivum, Avena sativa, and Secale cereale. 25256514 1 10 theme sibirica 254:261 arg1 L 263:263 Abies sibirica L 248:263 Abies sibirica L 248:263 Highly branched arabinan-rich pectic polysaccharides, containing 84% of arabinose, was extracted from wood greenery of Abies sibirica L. 25256514 0 11 theme pectins 105:111 arg1 activity 93:100 L. Biological activity 79:100 L. Biological activity of pectins of A. sibirica 79:126 Structural studies of arabinan-rich pectic polysaccharides from Abies sibirica L. Biological activity of pectins of A. sibirica. 25256514 4 12 link 1,5-linked 507:516 arg1 residues 527:534 1,5-linked α-L-Araf residues 507:534 1,5-linked α-L-Araf residues (the major part of polymer mass) 507:567 Side chains were comprised of 1,5-linked α-L-Araf residues (the major part of polymer mass), 1,3,5-di-O- and 1,2,3,5-tri-O-linked α-L-Araf residues, confirming the presence of highly branched 1,5-α-L-arabinan. 25256514 9 13 theme Triticum 1133:1140 arg1 germs 1114:1118 germs 1114:1118 germs 1114:1118 Galacturonan had a strongest stimulating effect on germination and growth rate of seeds, germs and roots of Triticum aestivum, Avena sativa, and Secale cereale. 25256514 9 13 theme Triticum 1133:1140 arg1 seeds 1107:1111 seeds 1107:1111 seeds 1107:1111 Galacturonan had a strongest stimulating effect on germination and growth rate of seeds, germs and roots of Triticum aestivum, Avena sativa, and Secale cereale. 25256514 9 13 theme Triticum 1133:1140 arg1 roots 1124:1128 roots 1124:1128 roots 1124:1128 Galacturonan had a strongest stimulating effect on germination and growth rate of seeds, germs and roots of Triticum aestivum, Avena sativa, and Secale cereale. 25256514 2 14 theme arabinan 283:290 arg1 structure 270:278 The structure 266:278 The structure of arabinan 266:290 The structure of arabinan was studied by the 1D and 2D NMR spectroscopy. 25256514 1 15 theme L 263:263 arg1 greenery 236:243 wood greenery 231:243 wood greenery of Abies sibirica L 231:263 Highly branched arabinan-rich pectic polysaccharides, containing 84% of arabinose, was extracted from wood greenery of Abies sibirica L. 25256514 3 16 theme macromolecule 343:355 arg1 backbone 357:364 The macromolecule backbone 339:364 The macromolecule backbone 339:364 The macromolecule backbone was represented mainly by RG-I (molar ratio GalA:Rha ∼ 1.3:1) patterns with high degree of rhamnose branching. 25256514 0 17 from Abies 64:68 arg1 polysaccharides 43:57 arabinan-rich pectic polysaccharides 22:57 arabinan-rich pectic polysaccharides from Abies 22:68 Structural studies of arabinan-rich pectic polysaccharides from Abies sibirica L. Biological activity of pectins of A. sibirica. 25256514 0 17 from Abies 64:68 arg1 studies 11:17 Structural studies 0:17 Structural studies of arabinan-rich pectic polysaccharides from Abies 0:68 Structural studies of arabinan-rich pectic polysaccharides from Abies sibirica L. Biological activity of pectins of A. sibirica. 25256514 4 18 theme branched 660:667 arg1 1,5-α-L-arabinan 669:684 highly branched 1,5-α-L-arabinan 653:684 highly branched 1,5-α-L-arabinan 653:684 Side chains were comprised of 1,5-linked α-L-Araf residues (the major part of polymer mass), 1,3,5-di-O- and 1,2,3,5-tri-O-linked α-L-Araf residues, confirming the presence of highly branched 1,5-α-L-arabinan. 25256514 1 19 theme branched 136:143 arg1 polysaccharides 166:180 Highly branched arabinan-rich pectic polysaccharides 129:180 Highly branched arabinan-rich pectic polysaccharides 129:180 Highly branched arabinan-rich pectic polysaccharides, containing 84% of arabinose, was extracted from wood greenery of Abies sibirica L. 25256514 4 20 dep residues 527:534 arg1 part 547:550 the major part 537:550 the major part of polymer mass 537:566 Side chains were comprised of 1,5-linked α-L-Araf residues (the major part of polymer mass), 1,3,5-di-O- and 1,2,3,5-tri-O-linked α-L-Araf residues, confirming the presence of highly branched 1,5-α-L-arabinan. 25256514 4 20 dep residues 527:534 arg1 confirming 626:635 confirming 626:635 confirming the presence of highly branched 1,5-α-L-arabinan 626:684 Side chains were comprised of 1,5-linked α-L-Araf residues (the major part of polymer mass), 1,3,5-di-O- and 1,2,3,5-tri-O-linked α-L-Araf residues, confirming the presence of highly branched 1,5-α-L-arabinan. 25256514 5 21 theme α-anomeric 716:725 arg1 form 727:730 α-anomeric form 716:730 α-anomeric form 716:730 Although most L-Araf were in α-anomeric form, minor terminal β-L-Araf-(1 →... was detected. 25256514 3 22 dep RG-I 392:395 arg1 ∼ 419:419 ∼ 419:419 ∼ 419:419 The macromolecule backbone was represented mainly by RG-I (molar ratio GalA:Rha ∼ 1.3:1) patterns with high degree of rhamnose branching. 25256514 6 23 located found 808:812 arg1 chains 826:831 the side chains 817:831 the side chains 817:831 1,4-β-D-linked Galp residues found in the side chains account for minor AG-I or 1,4-galactan, as compared to arabinan. 25256514 6 23 located found 808:812 arg2 residues 799:806 1,4-β-D-linked Galp residues 779:806 1,4-β-D-linked Galp residues found in the side chains 779:831 1,4-β-D-linked Galp residues found in the side chains account for minor AG-I or 1,4-galactan, as compared to arabinan. 25256514 4 24 theme polymer 555:561 arg1 mass 563:566 polymer mass 555:566 polymer mass 555:566 Side chains were comprised of 1,5-linked α-L-Araf residues (the major part of polymer mass), 1,3,5-di-O- and 1,2,3,5-tri-O-linked α-L-Araf residues, confirming the presence of highly branched 1,5-α-L-arabinan. 25256514 9 25 theme strongest 1044:1052 arg1 effect 1066:1071 a strongest stimulating effect 1042:1071 a strongest stimulating effect on germination and growth rate of seeds, germs and roots of Triticum aestivum, Avena sativa, and Secale cereale 1042:1183 Galacturonan had a strongest stimulating effect on germination and growth rate of seeds, germs and roots of Triticum aestivum, Avena sativa, and Secale cereale. 25256514 4 26 theme major 541:545 arg1 part 547:550 the major part 537:550 the major part of polymer mass 537:566 Side chains were comprised of 1,5-linked α-L-Araf residues (the major part of polymer mass), 1,3,5-di-O- and 1,2,3,5-tri-O-linked α-L-Araf residues, confirming the presence of highly branched 1,5-α-L-arabinan. 25256514 5 27 theme terminal 739:746 arg1 β-L-Araf- 748:756 minor terminal β-L-Araf- 733:756 minor terminal β-L-Araf-(1 →... 733:763 Although most L-Araf were in α-anomeric form, minor terminal β-L-Araf-(1 →... was detected. 25256514 5 28 dep β-L-Araf- 748:756 arg1 .. 761:762 .. 761:762 minor terminal β-L-Araf-(1 →... 733:763 Although most L-Araf were in α-anomeric form, minor terminal β-L-Araf-(1 →... was detected. 25256514 9 29 theme stimulating 1054:1064 arg1 effect 1066:1071 a strongest stimulating effect 1042:1071 a strongest stimulating effect on germination and growth rate of seeds, germs and roots of Triticum aestivum, Avena sativa, and Secale cereale 1042:1183 Galacturonan had a strongest stimulating effect on germination and growth rate of seeds, germs and roots of Triticum aestivum, Avena sativa, and Secale cereale. 25256514 0 30 theme Structural 0:9 arg1 studies 11:17 Structural studies 0:17 Structural studies of arabinan-rich pectic polysaccharides from Abies 0:68 Structural studies of arabinan-rich pectic polysaccharides from Abies sibirica L. Biological activity of pectins of A. sibirica. 25256514 4 31 theme α-L-Araf 518:525 arg1 residues 527:534 1,5-linked α-L-Araf residues 507:534 1,5-linked α-L-Araf residues (the major part of polymer mass) 507:567 Side chains were comprised of 1,5-linked α-L-Araf residues (the major part of polymer mass), 1,3,5-di-O- and 1,2,3,5-tri-O-linked α-L-Araf residues, confirming the presence of highly branched 1,5-α-L-arabinan. 25256514 8 32 theme fir 973:975 arg1 greenery 977:984 Siberian fir greenery 964:984 Siberian fir greenery 964:984 Polysaccharides obtained from Siberian fir greenery were screened for biological activity. 25256514 0 33 theme arabinan-rich 22:34 arg1 polysaccharides 43:57 arabinan-rich pectic polysaccharides 22:57 arabinan-rich pectic polysaccharides from Abies 22:68 Structural studies of arabinan-rich pectic polysaccharides from Abies sibirica L. Biological activity of pectins of A. sibirica. 25256514 4 34 theme 1,5-linked 507:516 arg1 residues 527:534 1,5-linked α-L-Araf residues 507:534 1,5-linked α-L-Araf residues (the major part of polymer mass) 507:567 Side chains were comprised of 1,5-linked α-L-Araf residues (the major part of polymer mass), 1,3,5-di-O- and 1,2,3,5-tri-O-linked α-L-Araf residues, confirming the presence of highly branched 1,5-α-L-arabinan. 25256514 8 35 theme Siberian 964:971 arg1 greenery 977:984 Siberian fir greenery 964:984 Siberian fir greenery 964:984 Polysaccharides obtained from Siberian fir greenery were screened for biological activity. 25256514 1 36 theme arabinose 201:209 arg1 % 196:196 84% 194:196 84% of arabinose 194:209 Highly branched arabinan-rich pectic polysaccharides, containing 84% of arabinose, was extracted from wood greenery of Abies sibirica L. 25256514 1 36 theme arabinose 201:209 arg1 arabinose 201:209 arabinose 201:209 arabinose 201:209 Highly branched arabinan-rich pectic polysaccharides, containing 84% of arabinose, was extracted from wood greenery of Abies sibirica L. 25256514 0 37 theme sibirica 119:126 arg1 pectins 105:111 pectins 105:111 pectins of A. sibirica 105:126 Structural studies of arabinan-rich pectic polysaccharides from Abies sibirica L. Biological activity of pectins of A. sibirica. 25256514 6 38 theme side 821:824 arg1 chains 826:831 the side chains 817:831 the side chains 817:831 1,4-β-D-linked Galp residues found in the side chains account for minor AG-I or 1,4-galactan, as compared to arabinan. 25256514 6 39 link 1,4-β-D-linked 779:792 arg1 residues 799:806 1,4-β-D-linked Galp residues 779:806 1,4-β-D-linked Galp residues found in the side chains 779:831 1,4-β-D-linked Galp residues found in the side chains account for minor AG-I or 1,4-galactan, as compared to arabinan. 25256514 0 40 theme polysaccharides 43:57 arg1 studies 11:17 Structural studies 0:17 Structural studies of arabinan-rich pectic polysaccharides from Abies 0:68 Structural studies of arabinan-rich pectic polysaccharides from Abies sibirica L. Biological activity of pectins of A. sibirica. 25256514 4 41 theme 1,5-α-L-arabinan 669:684 arg1 presence 641:648 the presence 637:648 the presence of highly branched 1,5-α-L-arabinan 637:684 Side chains were comprised of 1,5-linked α-L-Araf residues (the major part of polymer mass), 1,3,5-di-O- and 1,2,3,5-tri-O-linked α-L-Araf residues, confirming the presence of highly branched 1,5-α-L-arabinan. 25256514 9 42 theme cereale 1177:1183 arg1 germs 1114:1118 germs 1114:1118 germs 1114:1118 Galacturonan had a strongest stimulating effect on germination and growth rate of seeds, germs and roots of Triticum aestivum, Avena sativa, and Secale cereale. 25256514 9 42 theme cereale 1177:1183 arg1 seeds 1107:1111 seeds 1107:1111 seeds 1107:1111 Galacturonan had a strongest stimulating effect on germination and growth rate of seeds, germs and roots of Triticum aestivum, Avena sativa, and Secale cereale. 25256514 9 42 theme cereale 1177:1183 arg1 roots 1124:1128 roots 1124:1128 roots 1124:1128 Galacturonan had a strongest stimulating effect on germination and growth rate of seeds, germs and roots of Triticum aestivum, Avena sativa, and Secale cereale. 25256514 5 43 theme most 696:699 arg1 L-Araf 701:706 most L-Araf 696:706 most L-Araf 696:706 Although most L-Araf were in α-anomeric form, minor terminal β-L-Araf-(1 →... was detected. 25256514 9 44 dep Triticum 1133:1140 arg1 aestivum 1142:1149 Triticum aestivum 1133:1149 Triticum aestivum 1133:1149 Galacturonan had a strongest stimulating effect on germination and growth rate of seeds, germs and roots of Triticum aestivum, Avena sativa, and Secale cereale. 25256514 4 45 theme α-L-Araf 607:614 arg1 residues 616:623 1,2,3,5-tri-O-linked α-L-Araf residues 586:623 1,2,3,5-tri-O-linked α-L-Araf residues 586:623 Side chains were comprised of 1,5-linked α-L-Araf residues (the major part of polymer mass), 1,3,5-di-O- and 1,2,3,5-tri-O-linked α-L-Araf residues, confirming the presence of highly branched 1,5-α-L-arabinan. 25256514 0 46 theme pectic 36:41 arg1 polysaccharides 43:57 arabinan-rich pectic polysaccharides 22:57 arabinan-rich pectic polysaccharides from Abies 22:68 Structural studies of arabinan-rich pectic polysaccharides from Abies sibirica L. Biological activity of pectins of A. sibirica. 25256514 3 47 theme molar 398:402 arg1 ratio 404:408 molar ratio 398:408 molar ratio 398:408 The macromolecule backbone was represented mainly by RG-I (molar ratio GalA:Rha ∼ 1.3:1) patterns with high degree of rhamnose branching. 25256514 9 48 theme growth 1092:1097 arg1 rate 1099:1102 growth rate 1092:1102 growth rate 1092:1102 Galacturonan had a strongest stimulating effect on germination and growth rate of seeds, germs and roots of Triticum aestivum, Avena sativa, and Secale cereale. 25256514 4 49 theme Side 477:480 arg1 chains 482:487 Side chains 477:487 Side chains 477:487 Side chains were comprised of 1,5-linked α-L-Araf residues (the major part of polymer mass), 1,3,5-di-O- and 1,2,3,5-tri-O-linked α-L-Araf residues, confirming the presence of highly branched 1,5-α-L-arabinan. 25256514 4 50 theme 1,2,3,5-tri-O-linked 586:605 arg1 residues 616:623 1,2,3,5-tri-O-linked α-L-Araf residues 586:623 1,2,3,5-tri-O-linked α-L-Araf residues 586:623 Side chains were comprised of 1,5-linked α-L-Araf residues (the major part of polymer mass), 1,3,5-di-O- and 1,2,3,5-tri-O-linked α-L-Araf residues, confirming the presence of highly branched 1,5-α-L-arabinan. 25256514 1 51 contain containing 183:192 arg1 polysaccharides 166:180 Highly branched arabinan-rich pectic polysaccharides 129:180 Highly branched arabinan-rich pectic polysaccharides 129:180 Highly branched arabinan-rich pectic polysaccharides, containing 84% of arabinose, was extracted from wood greenery of Abies sibirica L. 25256514 1 51 contain containing 183:192 arg2 arabinose 201:209 arabinose 201:209 arabinose 201:209 Highly branched arabinan-rich pectic polysaccharides, containing 84% of arabinose, was extracted from wood greenery of Abies sibirica L. 25256514 1 51 contain containing 183:192 arg2 % 196:196 84% 194:196 84% of arabinose 194:209 Highly branched arabinan-rich pectic polysaccharides, containing 84% of arabinose, was extracted from wood greenery of Abies sibirica L. 25256514 9 52 from effect 1066:1071 arg1 germination 1076:1086 germination 1076:1086 germination 1076:1086 Galacturonan had a strongest stimulating effect on germination and growth rate of seeds, germs and roots of Triticum aestivum, Avena sativa, and Secale cereale. 25256514 9 52 from effect 1066:1071 arg1 rate 1099:1102 growth rate 1092:1102 growth rate 1092:1102 Galacturonan had a strongest stimulating effect on germination and growth rate of seeds, germs and roots of Triticum aestivum, Avena sativa, and Secale cereale. 25256514 2 53 theme NMR 321:323 arg1 spectroscopy 325:336 the 1D and 2D NMR spectroscopy 307:336 the 1D and 2D NMR spectroscopy 307:336 The structure of arabinan was studied by the 1D and 2D NMR spectroscopy. 25256514 3 54 theme RG-I 392:395 arg1 patterns 428:435 RG-I (molar ratio GalA:Rha ∼ 1.3:1) patterns 392:435 RG-I (molar ratio GalA:Rha ∼ 1.3:1) patterns with high degree of rhamnose branching 392:474 The macromolecule backbone was represented mainly by RG-I (molar ratio GalA:Rha ∼ 1.3:1) patterns with high degree of rhamnose branching. 25256514 8 55 theme biological 1004:1013 arg1 activity 1015:1022 biological activity 1004:1022 biological activity 1004:1022 Polysaccharides obtained from Siberian fir greenery were screened for biological activity. 25256514 2 56 theme 2D 318:319 arg1 spectroscopy 325:336 the 1D and 2D NMR spectroscopy 307:336 the 1D and 2D NMR spectroscopy 307:336 The structure of arabinan was studied by the 1D and 2D NMR spectroscopy. 25256514 6 57 theme Galp 794:797 arg1 residues 799:806 1,4-β-D-linked Galp residues 779:806 1,4-β-D-linked Galp residues found in the side chains 779:831 1,4-β-D-linked Galp residues found in the side chains account for minor AG-I or 1,4-galactan, as compared to arabinan. 25256514 3 58 dep ∼ 419:419 arg1 ratio 404:408 molar ratio 398:408 molar ratio 398:408 The macromolecule backbone was represented mainly by RG-I (molar ratio GalA:Rha ∼ 1.3:1) patterns with high degree of rhamnose branching. 25256514 3 58 dep ∼ 419:419 arg1 GalA 410:413 GalA 410:413 GalA 410:413 The macromolecule backbone was represented mainly by RG-I (molar ratio GalA:Rha ∼ 1.3:1) patterns with high degree of rhamnose branching. 25256514 9 59 theme seeds 1107:1111 arg1 effect 1066:1071 a strongest stimulating effect 1042:1071 a strongest stimulating effect on germination and growth rate of seeds, germs and roots of Triticum aestivum, Avena sativa, and Secale cereale 1042:1183 Galacturonan had a strongest stimulating effect on germination and growth rate of seeds, germs and roots of Triticum aestivum, Avena sativa, and Secale cereale. 25256514 9 60 theme Avena 1152:1156 arg1 germs 1114:1118 germs 1114:1118 germs 1114:1118 Galacturonan had a strongest stimulating effect on germination and growth rate of seeds, germs and roots of Triticum aestivum, Avena sativa, and Secale cereale. 25256514 9 60 theme Avena 1152:1156 arg1 seeds 1107:1111 seeds 1107:1111 seeds 1107:1111 Galacturonan had a strongest stimulating effect on germination and growth rate of seeds, germs and roots of Triticum aestivum, Avena sativa, and Secale cereale. 25256514 9 60 theme Avena 1152:1156 arg1 roots 1124:1128 roots 1124:1128 roots 1124:1128 Galacturonan had a strongest stimulating effect on germination and growth rate of seeds, germs and roots of Triticum aestivum, Avena sativa, and Secale cereale. 25256514 4 61 theme mass 563:566 arg1 part 547:550 the major part 537:550 the major part of polymer mass 537:566 Side chains were comprised of 1,5-linked α-L-Araf residues (the major part of polymer mass), 1,3,5-di-O- and 1,2,3,5-tri-O-linked α-L-Araf residues, confirming the presence of highly branched 1,5-α-L-arabinan. 25256514 3 62 with patterns 428:435 arg1 degree 447:452 high degree 442:452 high degree of rhamnose branching 442:474 The macromolecule backbone was represented mainly by RG-I (molar ratio GalA:Rha ∼ 1.3:1) patterns with high degree of rhamnose branching. 25256514 6 63 theme 1,4-β-D-linked 779:792 arg1 residues 799:806 1,4-β-D-linked Galp residues 779:806 1,4-β-D-linked Galp residues found in the side chains 779:831 1,4-β-D-linked Galp residues found in the side chains account for minor AG-I or 1,4-galactan, as compared to arabinan. 25256514 4 64 link 1,2,3,5-tri-O-linked 586:605 arg1 residues 616:623 1,2,3,5-tri-O-linked α-L-Araf residues 586:623 1,2,3,5-tri-O-linked α-L-Araf residues 586:623 Side chains were comprised of 1,5-linked α-L-Araf residues (the major part of polymer mass), 1,3,5-di-O- and 1,2,3,5-tri-O-linked α-L-Araf residues, confirming the presence of highly branched 1,5-α-L-arabinan. 25256514 2 65 theme 1D 311:312 arg1 spectroscopy 325:336 the 1D and 2D NMR spectroscopy 307:336 the 1D and 2D NMR spectroscopy 307:336 The structure of arabinan was studied by the 1D and 2D NMR spectroscopy. 25256514 9 66 contain had 1038:1040 arg2 effect 1066:1071 a strongest stimulating effect 1042:1071 a strongest stimulating effect on germination and growth rate of seeds, germs and roots of Triticum aestivum, Avena sativa, and Secale cereale 1042:1183 Galacturonan had a strongest stimulating effect on germination and growth rate of seeds, germs and roots of Triticum aestivum, Avena sativa, and Secale cereale. 25256514 9 66 contain had 1038:1040 arg1 Galacturonan 1025:1036 Galacturonan 1025:1036 Galacturonan 1025:1036 Galacturonan had a strongest stimulating effect on germination and growth rate of seeds, germs and roots of Triticum aestivum, Avena sativa, and Secale cereale. 25256514 1 67 theme wood 231:234 arg1 greenery 236:243 wood greenery 231:243 wood greenery of Abies sibirica L 231:263 Highly branched arabinan-rich pectic polysaccharides, containing 84% of arabinose, was extracted from wood greenery of Abies sibirica L. 25256514 0 68 theme L. 79:80 arg1 activity 93:100 L. Biological activity 79:100 L. Biological activity of pectins of A. sibirica 79:126 Structural studies of arabinan-rich pectic polysaccharides from Abies sibirica L. Biological activity of pectins of A. sibirica. 25256514 9 69 theme germs 1114:1118 arg1 effect 1066:1071 a strongest stimulating effect 1042:1071 a strongest stimulating effect on germination and growth rate of seeds, germs and roots of Triticum aestivum, Avena sativa, and Secale cereale 1042:1183 Galacturonan had a strongest stimulating effect on germination and growth rate of seeds, germs and roots of Triticum aestivum, Avena sativa, and Secale cereale. 25256514 1 70 theme arabinan-rich 145:157 arg1 polysaccharides 166:180 Highly branched arabinan-rich pectic polysaccharides 129:180 Highly branched arabinan-rich pectic polysaccharides 129:180 Highly branched arabinan-rich pectic polysaccharides, containing 84% of arabinose, was extracted from wood greenery of Abies sibirica L. 25256514 3 71 theme high 442:445 arg1 degree 447:452 high degree 442:452 high degree of rhamnose branching 442:474 The macromolecule backbone was represented mainly by RG-I (molar ratio GalA:Rha ∼ 1.3:1) patterns with high degree of rhamnose branching. 25256514 1 72 theme pectic 159:164 arg1 polysaccharides 166:180 Highly branched arabinan-rich pectic polysaccharides 129:180 Highly branched arabinan-rich pectic polysaccharides 129:180 Highly branched arabinan-rich pectic polysaccharides, containing 84% of arabinose, was extracted from wood greenery of Abies sibirica L. 25023666 0 0 theme glycosyltransferase 68:86 arg1 fold 88:91 a distinct glycosyltransferase fold 57:91 a distinct glycosyltransferase fold 57:91 The highly conserved domain of unknown function 1792 has a distinct glycosyltransferase fold. 25023666 3 1 theme X-ray 297:301 arg1 structure 320:328 a 1.34-Å resolution X-ray crystallographic structure 277:328 a 1.34-Å resolution X-ray crystallographic structure of a previously uncharacterized 'domain of unknown function' 1792 (DUF1792) 277:404 Here we report a 1.34-Å resolution X-ray crystallographic structure of a previously uncharacterized 'domain of unknown function' 1792 (DUF1792) and show that the domain adopts a new fold and is required for glycosylation of a family of serine-rich repeat streptococcal adhesins. 25023666 4 2 theme branch 658:663 arg1 point 665:669 the branch point 654:669 the branch point of the hexasaccharide O-linked to the serine-rich repeat of the bacterial adhesin, Fap1 of Streptococcus parasanguinis 654:788 Biochemical studies reveal that the domain is a glucosyltransferase, and it catalyses the transfer of glucose to the branch point of the hexasaccharide O-linked to the serine-rich repeat of the bacterial adhesin, Fap1 of Streptococcus parasanguinis. 25023666 0 3 theme distinct 59:66 arg1 fold 88:91 a distinct glycosyltransferase fold 57:91 a distinct glycosyltransferase fold 57:91 The highly conserved domain of unknown function 1792 has a distinct glycosyltransferase fold. 25023666 4 4 link O-linked 693:700 arg1 hexasaccharide 678:691 the hexasaccharide 674:691 the hexasaccharide O-linked to the serine-rich repeat of the bacterial adhesin, Fap1 of Streptococcus parasanguinis 674:788 Biochemical studies reveal that the domain is a glucosyltransferase, and it catalyses the transfer of glucose to the branch point of the hexasaccharide O-linked to the serine-rich repeat of the bacterial adhesin, Fap1 of Streptococcus parasanguinis. 25023666 4 5 theme Biochemical 541:551 arg1 studies 553:559 Biochemical studies 541:559 Biochemical studies 541:559 Biochemical studies reveal that the domain is a glucosyltransferase, and it catalyses the transfer of glucose to the branch point of the hexasaccharide O-linked to the serine-rich repeat of the bacterial adhesin, Fap1 of Streptococcus parasanguinis. 25023666 3 6 theme uncharacterized 346:360 arg1 domain 363:368 a previously uncharacterized 'domain 333:368 a previously uncharacterized 'domain of unknown function' 1792 (DUF1792) 333:404 Here we report a 1.34-Å resolution X-ray crystallographic structure of a previously uncharacterized 'domain of unknown function' 1792 (DUF1792) and show that the domain adopts a new fold and is required for glycosylation of a family of serine-rich repeat streptococcal adhesins. 25023666 3 6 theme uncharacterized 346:360 arg1 function 381:388 unknown function' 1792 373:394 unknown function' 1792 (DUF1792) 373:404 Here we report a 1.34-Å resolution X-ray crystallographic structure of a previously uncharacterized 'domain of unknown function' 1792 (DUF1792) and show that the domain adopts a new fold and is required for glycosylation of a family of serine-rich repeat streptococcal adhesins. 25023666 3 7 gly glycosylation 469:481 arg1 family 488:493 a family 486:493 a family of serine-rich repeat streptococcal adhesins 486:538 Here we report a 1.34-Å resolution X-ray crystallographic structure of a previously uncharacterized 'domain of unknown function' 1792 (DUF1792) and show that the domain adopts a new fold and is required for glycosylation of a family of serine-rich repeat streptococcal adhesins. 25023666 3 8 theme serine-rich 498:508 arg1 adhesins 531:538 serine-rich repeat streptococcal adhesins 498:538 serine-rich repeat streptococcal adhesins 498:538 Here we report a 1.34-Å resolution X-ray crystallographic structure of a previously uncharacterized 'domain of unknown function' 1792 (DUF1792) and show that the domain adopts a new fold and is required for glycosylation of a family of serine-rich repeat streptococcal adhesins. 25023666 2 9 theme Structural 154:163 arg1 studies 165:171 Structural studies 154:171 Structural studies 154:171 Structural studies, however, have only revealed two distinct glycosyltransferase (GT) folds, GT-A and GT-B. 25023666 7 10 theme new 1113:1115 arg1 it 1089:1090 it 1089:1090 it 1089:1090 As the domain is highly conserved in bacteria and not found in eukaryotes, it can be explored as a new antibacterial target. 25023666 7 10 theme new 1113:1115 arg1 target 1131:1136 a new antibacterial target 1111:1136 a new antibacterial target 1111:1136 As the domain is highly conserved in bacteria and not found in eukaryotes, it can be explored as a new antibacterial target. 25023666 4 11 theme bacterial 735:743 arg1 adhesin 745:751 the bacterial adhesin 731:751 the bacterial adhesin 731:751 Biochemical studies reveal that the domain is a glucosyltransferase, and it catalyses the transfer of glucose to the branch point of the hexasaccharide O-linked to the serine-rich repeat of the bacterial adhesin, Fap1 of Streptococcus parasanguinis. 25023666 3 12 theme family 488:493 arg1 glycosylation 469:481 glycosylation 469:481 glycosylation of a family of serine-rich repeat streptococcal adhesins 469:538 Here we report a 1.34-Å resolution X-ray crystallographic structure of a previously uncharacterized 'domain of unknown function' 1792 (DUF1792) and show that the domain adopts a new fold and is required for glycosylation of a family of serine-rich repeat streptococcal adhesins. 25023666 5 13 theme Gram-negative 838:850 arg1 bacteria 852:859 both Gram-positive and Gram-negative bacteria 815:859 both Gram-positive and Gram-negative bacteria 815:859 DUF1792 homologues from both Gram-positive and Gram-negative bacteria also exhibit the activity. 25023666 3 14 theme unknown 373:379 arg1 function 381:388 unknown function' 1792 373:394 unknown function' 1792 (DUF1792) 373:404 Here we report a 1.34-Å resolution X-ray crystallographic structure of a previously uncharacterized 'domain of unknown function' 1792 (DUF1792) and show that the domain adopts a new fold and is required for glycosylation of a family of serine-rich repeat streptococcal adhesins. 25023666 3 14 theme unknown 373:379 arg1 DUF1792 397:403 DUF1792 397:403 DUF1792 397:403 Here we report a 1.34-Å resolution X-ray crystallographic structure of a previously uncharacterized 'domain of unknown function' 1792 (DUF1792) and show that the domain adopts a new fold and is required for glycosylation of a family of serine-rich repeat streptococcal adhesins. 25023666 3 15 theme crystallographic 303:318 arg1 structure 320:328 a 1.34-Å resolution X-ray crystallographic structure 277:328 a 1.34-Å resolution X-ray crystallographic structure of a previously uncharacterized 'domain of unknown function' 1792 (DUF1792) 277:404 Here we report a 1.34-Å resolution X-ray crystallographic structure of a previously uncharacterized 'domain of unknown function' 1792 (DUF1792) and show that the domain adopts a new fold and is required for glycosylation of a family of serine-rich repeat streptococcal adhesins. 25023666 3 16 theme adhesins 531:538 arg1 family 488:493 a family 486:493 a family of serine-rich repeat streptococcal adhesins 486:538 Here we report a 1.34-Å resolution X-ray crystallographic structure of a previously uncharacterized 'domain of unknown function' 1792 (DUF1792) and show that the domain adopts a new fold and is required for glycosylation of a family of serine-rich repeat streptococcal adhesins. 25023666 7 17 theme antibacterial 1117:1129 arg1 it 1089:1090 it 1089:1090 it 1089:1090 As the domain is highly conserved in bacteria and not found in eukaryotes, it can be explored as a new antibacterial target. 25023666 7 17 theme antibacterial 1117:1129 arg1 target 1131:1136 a new antibacterial target 1111:1136 a new antibacterial target 1111:1136 As the domain is highly conserved in bacteria and not found in eukaryotes, it can be explored as a new antibacterial target. 25023666 3 18 theme function 381:388 arg1 domain 363:368 a previously uncharacterized 'domain 333:368 a previously uncharacterized 'domain of unknown function' 1792 (DUF1792) 333:404 Here we report a 1.34-Å resolution X-ray crystallographic structure of a previously uncharacterized 'domain of unknown function' 1792 (DUF1792) and show that the domain adopts a new fold and is required for glycosylation of a family of serine-rich repeat streptococcal adhesins. 25023666 3 18 theme function 381:388 arg1 function 381:388 unknown function' 1792 373:394 unknown function' 1792 (DUF1792) 373:404 Here we report a 1.34-Å resolution X-ray crystallographic structure of a previously uncharacterized 'domain of unknown function' 1792 (DUF1792) and show that the domain adopts a new fold and is required for glycosylation of a family of serine-rich repeat streptococcal adhesins. 25023666 4 19 theme O-linked 693:700 arg1 hexasaccharide 678:691 the hexasaccharide 674:691 the hexasaccharide O-linked to the serine-rich repeat of the bacterial adhesin, Fap1 of Streptococcus parasanguinis 674:788 Biochemical studies reveal that the domain is a glucosyltransferase, and it catalyses the transfer of glucose to the branch point of the hexasaccharide O-linked to the serine-rich repeat of the bacterial adhesin, Fap1 of Streptococcus parasanguinis. 25023666 3 20 theme domain 363:368 arg1 structure 320:328 a 1.34-Å resolution X-ray crystallographic structure 277:328 a 1.34-Å resolution X-ray crystallographic structure of a previously uncharacterized 'domain of unknown function' 1792 (DUF1792) 277:404 Here we report a 1.34-Å resolution X-ray crystallographic structure of a previously uncharacterized 'domain of unknown function' 1792 (DUF1792) and show that the domain adopts a new fold and is required for glycosylation of a family of serine-rich repeat streptococcal adhesins. 25023666 3 21 theme repeat 510:515 arg1 adhesins 531:538 serine-rich repeat streptococcal adhesins 498:538 serine-rich repeat streptococcal adhesins 498:538 Here we report a 1.34-Å resolution X-ray crystallographic structure of a previously uncharacterized 'domain of unknown function' 1792 (DUF1792) and show that the domain adopts a new fold and is required for glycosylation of a family of serine-rich repeat streptococcal adhesins. 25023666 0 22 theme conserved 11:19 arg1 domain 21:26 The highly conserved domain 0:26 The highly conserved domain of unknown function 1792 0:51 The highly conserved domain of unknown function 1792 has a distinct glycosyltransferase fold. 25023666 0 22 theme conserved 11:19 arg1 function 39:46 unknown function 1792 31:51 unknown function 1792 31:51 The highly conserved domain of unknown function 1792 has a distinct glycosyltransferase fold. 25023666 3 23 theme streptococcal 517:529 arg1 adhesins 531:538 serine-rich repeat streptococcal adhesins 498:538 serine-rich repeat streptococcal adhesins 498:538 Here we report a 1.34-Å resolution X-ray crystallographic structure of a previously uncharacterized 'domain of unknown function' 1792 (DUF1792) and show that the domain adopts a new fold and is required for glycosylation of a family of serine-rich repeat streptococcal adhesins. 25023666 2 24 dep glycosyltransferase 215:233 arg1 folds 240:244 folds 240:244 folds 240:244 Structural studies, however, have only revealed two distinct glycosyltransferase (GT) folds, GT-A and GT-B. 25023666 0 25 theme unknown 31:37 arg1 function 39:46 unknown function 1792 31:51 unknown function 1792 31:51 The highly conserved domain of unknown function 1792 has a distinct glycosyltransferase fold. 25023666 6 26 theme glycosyltransferases 929:948 arg1 family 919:924 a new family 913:924 a new family of glycosyltransferases 913:948 Thus, DUF1792 represents a new family of glycosyltransferases; therefore, we designate it as a GT-D glycosyltransferase fold. 25023666 4 27 theme parasanguinis 776:788 arg1 Fap1 754:757 Fap1 754:757 Fap1 of Streptococcus parasanguinis 754:788 Biochemical studies reveal that the domain is a glucosyltransferase, and it catalyses the transfer of glucose to the branch point of the hexasaccharide O-linked to the serine-rich repeat of the bacterial adhesin, Fap1 of Streptococcus parasanguinis. 25023666 4 27 theme parasanguinis 776:788 arg1 repeat 721:726 the serine-rich repeat 705:726 the serine-rich repeat of the bacterial adhesin 705:751 Biochemical studies reveal that the domain is a glucosyltransferase, and it catalyses the transfer of glucose to the branch point of the hexasaccharide O-linked to the serine-rich repeat of the bacterial adhesin, Fap1 of Streptococcus parasanguinis. 25023666 5 28 theme Gram-positive 820:832 arg1 bacteria 852:859 both Gram-positive and Gram-negative bacteria 815:859 both Gram-positive and Gram-negative bacteria 815:859 DUF1792 homologues from both Gram-positive and Gram-negative bacteria also exhibit the activity. 25023666 3 29 theme 1.34-Å 279:284 arg1 structure 320:328 a 1.34-Å resolution X-ray crystallographic structure 277:328 a 1.34-Å resolution X-ray crystallographic structure of a previously uncharacterized 'domain of unknown function' 1792 (DUF1792) 277:404 Here we report a 1.34-Å resolution X-ray crystallographic structure of a previously uncharacterized 'domain of unknown function' 1792 (DUF1792) and show that the domain adopts a new fold and is required for glycosylation of a family of serine-rich repeat streptococcal adhesins. 25023666 0 30 theme function 39:46 arg1 domain 21:26 The highly conserved domain 0:26 The highly conserved domain of unknown function 1792 0:51 The highly conserved domain of unknown function 1792 has a distinct glycosyltransferase fold. 25023666 0 30 theme function 39:46 arg1 function 39:46 unknown function 1792 31:51 unknown function 1792 31:51 The highly conserved domain of unknown function 1792 has a distinct glycosyltransferase fold. 25023666 6 31 theme new 915:917 arg1 family 919:924 a new family 913:924 a new family of glycosyltransferases 913:948 Thus, DUF1792 represents a new family of glycosyltransferases; therefore, we designate it as a GT-D glycosyltransferase fold. 25023666 3 32 theme resolution 286:295 arg1 structure 320:328 a 1.34-Å resolution X-ray crystallographic structure 277:328 a 1.34-Å resolution X-ray crystallographic structure of a previously uncharacterized 'domain of unknown function' 1792 (DUF1792) 277:404 Here we report a 1.34-Å resolution X-ray crystallographic structure of a previously uncharacterized 'domain of unknown function' 1792 (DUF1792) and show that the domain adopts a new fold and is required for glycosylation of a family of serine-rich repeat streptococcal adhesins. 25023666 2 33 theme distinct 206:213 arg1 GT 236:237 GT 236:237 GT 236:237 Structural studies, however, have only revealed two distinct glycosyltransferase (GT) folds, GT-A and GT-B. 25023666 2 33 theme distinct 206:213 arg1 glycosyltransferase 215:233 two distinct glycosyltransferase 202:233 two distinct glycosyltransferase (GT) folds 202:244 Structural studies, however, have only revealed two distinct glycosyltransferase (GT) folds, GT-A and GT-B. 25023666 2 33 theme distinct 206:213 arg1 GT-A 247:250 GT-A 247:250 GT-A 247:250 Structural studies, however, have only revealed two distinct glycosyltransferase (GT) folds, GT-A and GT-B. 25023666 2 33 theme distinct 206:213 arg1 GT-B 256:259 GT-B 256:259 GT-B 256:259 Structural studies, however, have only revealed two distinct glycosyltransferase (GT) folds, GT-A and GT-B. 25023666 6 34 theme glycosyltransferase 988:1006 arg1 it 975:976 it 975:976 it 975:976 Thus, DUF1792 represents a new family of glycosyltransferases; therefore, we designate it as a GT-D glycosyltransferase fold. 25023666 6 34 theme glycosyltransferase 988:1006 arg1 fold 1008:1011 a GT-D glycosyltransferase fold 981:1011 a GT-D glycosyltransferase fold 981:1011 Thus, DUF1792 represents a new family of glycosyltransferases; therefore, we designate it as a GT-D glycosyltransferase fold. 25023666 3 35 theme new 440:442 arg1 fold 444:447 a new fold 438:447 a new fold 438:447 Here we report a 1.34-Å resolution X-ray crystallographic structure of a previously uncharacterized 'domain of unknown function' 1792 (DUF1792) and show that the domain adopts a new fold and is required for glycosylation of a family of serine-rich repeat streptococcal adhesins. 25023666 4 36 theme serine-rich 709:719 arg1 Fap1 754:757 Fap1 754:757 Fap1 of Streptococcus parasanguinis 754:788 Biochemical studies reveal that the domain is a glucosyltransferase, and it catalyses the transfer of glucose to the branch point of the hexasaccharide O-linked to the serine-rich repeat of the bacterial adhesin, Fap1 of Streptococcus parasanguinis. 25023666 4 36 theme serine-rich 709:719 arg1 repeat 721:726 the serine-rich repeat 705:726 the serine-rich repeat of the bacterial adhesin 705:751 Biochemical studies reveal that the domain is a glucosyltransferase, and it catalyses the transfer of glucose to the branch point of the hexasaccharide O-linked to the serine-rich repeat of the bacterial adhesin, Fap1 of Streptococcus parasanguinis. 25023666 4 37 theme adhesin 745:751 arg1 Fap1 754:757 Fap1 754:757 Fap1 of Streptococcus parasanguinis 754:788 Biochemical studies reveal that the domain is a glucosyltransferase, and it catalyses the transfer of glucose to the branch point of the hexasaccharide O-linked to the serine-rich repeat of the bacterial adhesin, Fap1 of Streptococcus parasanguinis. 25023666 4 37 theme adhesin 745:751 arg1 repeat 721:726 the serine-rich repeat 705:726 the serine-rich repeat of the bacterial adhesin 705:751 Biochemical studies reveal that the domain is a glucosyltransferase, and it catalyses the transfer of glucose to the branch point of the hexasaccharide O-linked to the serine-rich repeat of the bacterial adhesin, Fap1 of Streptococcus parasanguinis. 25023666 5 38 from bacteria 852:859 arg1 homologues 799:808 DUF1792 homologues 791:808 DUF1792 homologues from both Gram-positive and Gram-negative bacteria 791:859 DUF1792 homologues from both Gram-positive and Gram-negative bacteria also exhibit the activity. 25023666 4 39 theme hexasaccharide 678:691 arg1 point 665:669 the branch point 654:669 the branch point of the hexasaccharide O-linked to the serine-rich repeat of the bacterial adhesin, Fap1 of Streptococcus parasanguinis 654:788 Biochemical studies reveal that the domain is a glucosyltransferase, and it catalyses the transfer of glucose to the branch point of the hexasaccharide O-linked to the serine-rich repeat of the bacterial adhesin, Fap1 of Streptococcus parasanguinis. 25023666 6 40 theme GT-D 983:986 arg1 it 975:976 it 975:976 it 975:976 Thus, DUF1792 represents a new family of glycosyltransferases; therefore, we designate it as a GT-D glycosyltransferase fold. 25023666 6 40 theme GT-D 983:986 arg1 fold 1008:1011 a GT-D glycosyltransferase fold 981:1011 a GT-D glycosyltransferase fold 981:1011 Thus, DUF1792 represents a new family of glycosyltransferases; therefore, we designate it as a GT-D glycosyltransferase fold. 25023666 5 41 theme DUF1792 791:797 arg1 homologues 799:808 DUF1792 homologues 791:808 DUF1792 homologues from both Gram-positive and Gram-negative bacteria 791:859 DUF1792 homologues from both Gram-positive and Gram-negative bacteria also exhibit the activity. 25023666 0 42 contain has 53:55 arg1 domain 21:26 The highly conserved domain 0:26 The highly conserved domain of unknown function 1792 0:51 The highly conserved domain of unknown function 1792 has a distinct glycosyltransferase fold. 25023666 0 42 contain has 53:55 arg1 function 39:46 unknown function 1792 31:51 unknown function 1792 31:51 The highly conserved domain of unknown function 1792 has a distinct glycosyltransferase fold. 25023666 0 42 contain has 53:55 arg2 fold 88:91 a distinct glycosyltransferase fold 57:91 a distinct glycosyltransferase fold 57:91 The highly conserved domain of unknown function 1792 has a distinct glycosyltransferase fold. 25023666 4 43 theme glucose 643:649 arg1 transfer 631:638 the transfer 627:638 the transfer of glucose to the branch point of the hexasaccharide O-linked to the serine-rich repeat of the bacterial adhesin, Fap1 of Streptococcus parasanguinis 627:788 Biochemical studies reveal that the domain is a glucosyltransferase, and it catalyses the transfer of glucose to the branch point of the hexasaccharide O-linked to the serine-rich repeat of the bacterial adhesin, Fap1 of Streptococcus parasanguinis. 24802710 3 0 theme Western 389:395 arg1 METHODS 356:362 METHODS Immunohistochemistry and Western blot 356:400 METHODS Immunohistochemistry and Western blot 356:400 METHODS Immunohistochemistry and Western blot were performed to demonstrate O-GlcNAcylation in keratinocyte differentiation. 24802710 3 0 theme Western 389:395 arg1 blot 397:400 Western blot 389:400 Western blot 389:400 METHODS Immunohistochemistry and Western blot were performed to demonstrate O-GlcNAcylation in keratinocyte differentiation. 24802710 8 1 from activity 905:912 arg1 terms 926:930 terms 926:930 terms of involucrin and loricrin promoter activities 926:977 Interestingly, transcriptional activity of Sp-1, in terms of involucrin and loricrin promoter activities, was markedly increased by overexpression of O-GlcNAcase (OGA). 24802710 9 2 from form 1234:1237 arg1 differentiation 1255:1269 keratinocyte differentiation 1242:1269 keratinocyte differentiation 1242:1269 In addition, membrane permeable non-O-GlcNAcylated Sp-1 did show transcriptional activity, while membrane permeable O-GlcNAcylated Sp-1 did not, suggesting O-GlcNAcylated Sp-1 is an inactive form in keratinocyte differentiation. 24802710 8 3 theme promoter 959:966 arg1 activities 968:977 promoter activities 959:977 promoter activities 959:977 Interestingly, transcriptional activity of Sp-1, in terms of involucrin and loricrin promoter activities, was markedly increased by overexpression of O-GlcNAcase (OGA). 24802710 4 4 theme calcium-induced 496:510 arg1 differentiation 525:539 calcium-induced keratinocyte differentiation 496:539 calcium-induced keratinocyte differentiation 496:539 RESULTS During calcium-induced keratinocyte differentiation, overall O-GlcNAcylation was decreased in a temporal manner. 24802710 4 5 gly O-GlcNAcylation 550:564 arg1 manner 594:599 a temporal manner 583:599 a temporal manner 583:599 RESULTS During calcium-induced keratinocyte differentiation, overall O-GlcNAcylation was decreased in a temporal manner. 24802710 8 6 theme loricrin 950:957 arg1 terms 926:930 terms 926:930 terms of involucrin and loricrin promoter activities 926:977 Interestingly, transcriptional activity of Sp-1, in terms of involucrin and loricrin promoter activities, was markedly increased by overexpression of O-GlcNAcase (OGA). 24802710 9 7 theme transcriptional 1108:1122 arg1 activity 1124:1131 transcriptional activity 1108:1131 transcriptional activity 1108:1131 In addition, membrane permeable non-O-GlcNAcylated Sp-1 did show transcriptional activity, while membrane permeable O-GlcNAcylated Sp-1 did not, suggesting O-GlcNAcylated Sp-1 is an inactive form in keratinocyte differentiation. 24802710 9 8 theme O-GlcNAcylated 1159:1172 arg1 Sp-1 1174:1177 membrane permeable O-GlcNAcylated Sp-1 1140:1177 membrane permeable O-GlcNAcylated Sp-1 1140:1177 In addition, membrane permeable non-O-GlcNAcylated Sp-1 did show transcriptional activity, while membrane permeable O-GlcNAcylated Sp-1 did not, suggesting O-GlcNAcylated Sp-1 is an inactive form in keratinocyte differentiation. 24802710 1 9 theme O-linked 74:81 arg1 modification 116:127 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) modification 63:127 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) modification 63:127 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) modification is one of the posttranslational modification, emerging as an important regulatory mechanism in various cellular events. 24802710 8 10 theme O-GlcNAcase 1024:1034 arg1 overexpression 1006:1019 overexpression 1006:1019 overexpression of O-GlcNAcase (OGA) 1006:1040 Interestingly, transcriptional activity of Sp-1, in terms of involucrin and loricrin promoter activities, was markedly increased by overexpression of O-GlcNAcase (OGA). 24802710 3 11 dep METHODS 356:362 arg1 METHODS 356:362 METHODS Immunohistochemistry and Western blot 356:400 METHODS Immunohistochemistry and Western blot 356:400 METHODS Immunohistochemistry and Western blot were performed to demonstrate O-GlcNAcylation in keratinocyte differentiation. 24802710 3 11 dep METHODS 356:362 arg1 Immunohistochemistry 364:383 Immunohistochemistry 364:383 Immunohistochemistry 364:383 METHODS Immunohistochemistry and Western blot were performed to demonstrate O-GlcNAcylation in keratinocyte differentiation. 24802710 3 11 dep METHODS 356:362 arg1 blot 397:400 Western blot 389:400 Western blot 389:400 METHODS Immunohistochemistry and Western blot were performed to demonstrate O-GlcNAcylation in keratinocyte differentiation. 24802710 1 12 theme β-N-acetylglucosamine 83:103 arg1 modification 116:127 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) modification 63:127 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) modification 63:127 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) modification is one of the posttranslational modification, emerging as an important regulatory mechanism in various cellular events. 24802710 2 13 theme keratinocyte 326:337 arg1 differentiation 339:353 keratinocyte differentiation 326:353 keratinocyte differentiation 326:353 OBJECTIVE We attempted to investigate whether O-GlcNAcylation is involved in keratinocyte differentiation. 24802710 1 14 link O-linked 74:81 arg1 modification 116:127 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) modification 63:127 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) modification 63:127 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) modification is one of the posttranslational modification, emerging as an important regulatory mechanism in various cellular events. 24802710 8 15 dep involucrin 935:944 arg1 activities 968:977 promoter activities 959:977 promoter activities 959:977 Interestingly, transcriptional activity of Sp-1, in terms of involucrin and loricrin promoter activities, was markedly increased by overexpression of O-GlcNAcase (OGA). 24802710 2 16 dep OBJECTIVE 249:257 arg1 We 259:260 We 259:260 We 259:260 OBJECTIVE We attempted to investigate whether O-GlcNAcylation is involved in keratinocyte differentiation. 24802710 1 17 theme important 190:198 arg1 mechanism 211:219 an important regulatory mechanism 187:219 an important regulatory mechanism in various cellular events 187:246 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) modification is one of the posttranslational modification, emerging as an important regulatory mechanism in various cellular events. 24802710 1 18 theme O-GlcNAc 106:113 arg1 modification 116:127 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) modification 63:127 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) modification 63:127 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) modification is one of the posttranslational modification, emerging as an important regulatory mechanism in various cellular events. 24802710 1 19 theme regulatory 200:209 arg1 mechanism 211:219 an important regulatory mechanism 187:219 an important regulatory mechanism in various cellular events 187:246 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) modification is one of the posttranslational modification, emerging as an important regulatory mechanism in various cellular events. 24802710 2 20 gly O-GlcNAcylation 295:309 arg1 differentiation 339:353 keratinocyte differentiation 326:353 keratinocyte differentiation 326:353 OBJECTIVE We attempted to investigate whether O-GlcNAcylation is involved in keratinocyte differentiation. 24802710 9 21 theme O-GlcNAcylated 1199:1212 arg1 form 1234:1237 an inactive form 1222:1237 an inactive form in keratinocyte differentiation 1222:1269 In addition, membrane permeable non-O-GlcNAcylated Sp-1 did show transcriptional activity, while membrane permeable O-GlcNAcylated Sp-1 did not, suggesting O-GlcNAcylated Sp-1 is an inactive form in keratinocyte differentiation. 24802710 9 21 theme O-GlcNAcylated 1199:1212 arg1 Sp-1 1214:1217 O-GlcNAcylated Sp-1 1199:1217 O-GlcNAcylated Sp-1 1199:1217 In addition, membrane permeable non-O-GlcNAcylated Sp-1 did show transcriptional activity, while membrane permeable O-GlcNAcylated Sp-1 did not, suggesting O-GlcNAcylated Sp-1 is an inactive form in keratinocyte differentiation. 24802710 5 22 theme transcription 630:642 arg1 Sp-1 651:654 transcription factor Sp-1 630:654 transcription factor Sp-1 630:654 We focused our attention on transcription factor Sp-1, which is implicated in keratinocyte differentiation. 24802710 9 23 theme permeable 1149:1157 arg1 Sp-1 1174:1177 membrane permeable O-GlcNAcylated Sp-1 1140:1177 membrane permeable O-GlcNAcylated Sp-1 1140:1177 In addition, membrane permeable non-O-GlcNAcylated Sp-1 did show transcriptional activity, while membrane permeable O-GlcNAcylated Sp-1 did not, suggesting O-GlcNAcylated Sp-1 is an inactive form in keratinocyte differentiation. 24802710 10 24 theme regulatory 1336:1345 arg1 mechanism 1347:1355 a dynamic regulatory mechanism 1326:1355 a dynamic regulatory mechanism for keratinocyte differentiation 1326:1388 CONCLUSION Our results reveal that O-GlcNAcylation is a dynamic regulatory mechanism for keratinocyte differentiation. 24802710 10 24 theme regulatory 1336:1345 arg1 O-GlcNAcylation 1307:1321 O-GlcNAcylation 1307:1321 O-GlcNAcylation 1307:1321 CONCLUSION Our results reveal that O-GlcNAcylation is a dynamic regulatory mechanism for keratinocyte differentiation. 24802710 3 25 theme keratinocyte 451:462 arg1 differentiation 464:478 keratinocyte differentiation 451:478 keratinocyte differentiation 451:478 METHODS Immunohistochemistry and Western blot were performed to demonstrate O-GlcNAcylation in keratinocyte differentiation. 24802710 10 26 theme dynamic 1328:1334 arg1 mechanism 1347:1355 a dynamic regulatory mechanism 1326:1355 a dynamic regulatory mechanism for keratinocyte differentiation 1326:1388 CONCLUSION Our results reveal that O-GlcNAcylation is a dynamic regulatory mechanism for keratinocyte differentiation. 24802710 10 26 theme dynamic 1328:1334 arg1 O-GlcNAcylation 1307:1321 O-GlcNAcylation 1307:1321 O-GlcNAcylation 1307:1321 CONCLUSION Our results reveal that O-GlcNAcylation is a dynamic regulatory mechanism for keratinocyte differentiation. 24802710 4 27 theme keratinocyte 512:523 arg1 differentiation 525:539 calcium-induced keratinocyte differentiation 496:539 calcium-induced keratinocyte differentiation 496:539 RESULTS During calcium-induced keratinocyte differentiation, overall O-GlcNAcylation was decreased in a temporal manner. 24802710 1 28 theme various 224:230 arg1 events 241:246 various cellular events 224:246 various cellular events 224:246 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) modification is one of the posttranslational modification, emerging as an important regulatory mechanism in various cellular events. 24802710 0 29 theme keratinocyte 14:25 arg1 differentiation 27:41 keratinocyte differentiation 14:41 keratinocyte differentiation 14:41 Regulation of keratinocyte differentiation by O-GlcNAcylation. 24802710 1 30 theme cellular 232:239 arg1 events 241:246 various cellular events 224:246 various cellular events 224:246 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) modification is one of the posttranslational modification, emerging as an important regulatory mechanism in various cellular events. 24802710 6 31 theme Sp-1 716:719 arg1 level 721:725 Total Sp-1 level 710:725 Total Sp-1 level 710:725 Total Sp-1 level did not change during keratinocyte differentiation. 24802710 8 32 theme transcriptional 889:903 arg1 activity 905:912 transcriptional activity 889:912 transcriptional activity 889:912 Interestingly, transcriptional activity of Sp-1, in terms of involucrin and loricrin promoter activities, was markedly increased by overexpression of O-GlcNAcase (OGA). 24802710 6 33 theme keratinocyte 749:760 arg1 differentiation 762:776 keratinocyte differentiation 749:776 keratinocyte differentiation 749:776 Total Sp-1 level did not change during keratinocyte differentiation. 24802710 6 34 theme Total 710:714 arg1 level 721:725 Total Sp-1 level 710:725 Total Sp-1 level 710:725 Total Sp-1 level did not change during keratinocyte differentiation. 24802710 8 35 theme Sp-1 917:920 arg1 activity 905:912 transcriptional activity 889:912 transcriptional activity 889:912 Interestingly, transcriptional activity of Sp-1, in terms of involucrin and loricrin promoter activities, was markedly increased by overexpression of O-GlcNAcase (OGA). 24802710 4 36 theme temporal 585:592 arg1 manner 594:599 a temporal manner 583:599 a temporal manner 583:599 RESULTS During calcium-induced keratinocyte differentiation, overall O-GlcNAcylation was decreased in a temporal manner. 24802710 0 37 theme differentiation 27:41 arg1 Regulation 0:9 Regulation 0:9 Regulation of keratinocyte differentiation by O-GlcNAcylation. 0:61 Regulation of keratinocyte differentiation by O-GlcNAcylation. 24802710 10 38 theme keratinocyte 1361:1372 arg1 differentiation 1374:1388 keratinocyte differentiation 1361:1388 keratinocyte differentiation 1361:1388 CONCLUSION Our results reveal that O-GlcNAcylation is a dynamic regulatory mechanism for keratinocyte differentiation. 24802710 7 39 theme differentiation-dependent 840:864 arg1 manner 866:871 a keratinocyte differentiation-dependent manner 825:871 a keratinocyte differentiation-dependent manner 825:871 However, O-GlcNAcylated Sp-1 was decreased in a keratinocyte differentiation-dependent manner. 24802710 9 40 theme membrane 1140:1147 arg1 Sp-1 1174:1177 membrane permeable O-GlcNAcylated Sp-1 1140:1177 membrane permeable O-GlcNAcylated Sp-1 1140:1177 In addition, membrane permeable non-O-GlcNAcylated Sp-1 did show transcriptional activity, while membrane permeable O-GlcNAcylated Sp-1 did not, suggesting O-GlcNAcylated Sp-1 is an inactive form in keratinocyte differentiation. 24802710 4 41 theme overall 542:548 arg1 O-GlcNAcylation 550:564 overall O-GlcNAcylation 542:564 overall O-GlcNAcylation 542:564 RESULTS During calcium-induced keratinocyte differentiation, overall O-GlcNAcylation was decreased in a temporal manner. 24802710 7 42 theme keratinocyte 827:838 arg1 manner 866:871 a keratinocyte differentiation-dependent manner 825:871 a keratinocyte differentiation-dependent manner 825:871 However, O-GlcNAcylated Sp-1 was decreased in a keratinocyte differentiation-dependent manner. 24802710 4 43 dep RESULTS 481:487 arg1 decreased 570:578 decreased 570:578 was decreased in a temporal manner 566:599 RESULTS During calcium-induced keratinocyte differentiation, overall O-GlcNAcylation was decreased in a temporal manner. 24802710 9 44 theme membrane 1056:1063 arg1 Sp-1 1094:1097 membrane permeable non-O-GlcNAcylated Sp-1 1056:1097 membrane permeable non-O-GlcNAcylated Sp-1 1056:1097 In addition, membrane permeable non-O-GlcNAcylated Sp-1 did show transcriptional activity, while membrane permeable O-GlcNAcylated Sp-1 did not, suggesting O-GlcNAcylated Sp-1 is an inactive form in keratinocyte differentiation. 24802710 5 45 theme keratinocyte 680:691 arg1 differentiation 693:707 keratinocyte differentiation 680:707 keratinocyte differentiation 680:707 We focused our attention on transcription factor Sp-1, which is implicated in keratinocyte differentiation. 24802710 1 46 theme posttranslational 143:159 arg1 modification 161:172 the posttranslational modification 139:172 the posttranslational modification 139:172 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) modification is one of the posttranslational modification, emerging as an important regulatory mechanism in various cellular events. 24802710 9 47 theme permeable 1065:1073 arg1 Sp-1 1094:1097 membrane permeable non-O-GlcNAcylated Sp-1 1056:1097 membrane permeable non-O-GlcNAcylated Sp-1 1056:1097 In addition, membrane permeable non-O-GlcNAcylated Sp-1 did show transcriptional activity, while membrane permeable O-GlcNAcylated Sp-1 did not, suggesting O-GlcNAcylated Sp-1 is an inactive form in keratinocyte differentiation. 24802710 1 48 from mechanism 211:219 arg1 events 241:246 various cellular events 224:246 various cellular events 224:246 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) modification is one of the posttranslational modification, emerging as an important regulatory mechanism in various cellular events. 24802710 1 49 theme modification 161:172 arg1 modification 161:172 the posttranslational modification 139:172 the posttranslational modification 139:172 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) modification is one of the posttranslational modification, emerging as an important regulatory mechanism in various cellular events. 24802710 1 49 theme modification 161:172 arg1 one 132:134 one 132:134 one 132:134 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) modification is one of the posttranslational modification, emerging as an important regulatory mechanism in various cellular events. 24802710 9 50 theme non-O-GlcNAcylated 1075:1092 arg1 Sp-1 1094:1097 membrane permeable non-O-GlcNAcylated Sp-1 1056:1097 membrane permeable non-O-GlcNAcylated Sp-1 1056:1097 In addition, membrane permeable non-O-GlcNAcylated Sp-1 did show transcriptional activity, while membrane permeable O-GlcNAcylated Sp-1 did not, suggesting O-GlcNAcylated Sp-1 is an inactive form in keratinocyte differentiation. 24802710 9 51 theme keratinocyte 1242:1253 arg1 differentiation 1255:1269 keratinocyte differentiation 1242:1269 keratinocyte differentiation 1242:1269 In addition, membrane permeable non-O-GlcNAcylated Sp-1 did show transcriptional activity, while membrane permeable O-GlcNAcylated Sp-1 did not, suggesting O-GlcNAcylated Sp-1 is an inactive form in keratinocyte differentiation. 24802710 7 52 theme O-GlcNAcylated 788:801 arg1 Sp-1 803:806 O-GlcNAcylated Sp-1 788:806 O-GlcNAcylated Sp-1 788:806 However, O-GlcNAcylated Sp-1 was decreased in a keratinocyte differentiation-dependent manner. 24802710 1 53 theme BACKGROUND 63:72 arg1 modification 116:127 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) modification 63:127 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) modification 63:127 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) modification is one of the posttranslational modification, emerging as an important regulatory mechanism in various cellular events. 24802710 5 54 theme factor 644:649 arg1 Sp-1 651:654 transcription factor Sp-1 630:654 transcription factor Sp-1 630:654 We focused our attention on transcription factor Sp-1, which is implicated in keratinocyte differentiation. 24802710 9 55 theme inactive 1225:1232 arg1 form 1234:1237 an inactive form 1222:1237 an inactive form in keratinocyte differentiation 1222:1269 In addition, membrane permeable non-O-GlcNAcylated Sp-1 did show transcriptional activity, while membrane permeable O-GlcNAcylated Sp-1 did not, suggesting O-GlcNAcylated Sp-1 is an inactive form in keratinocyte differentiation. 24802710 9 55 theme inactive 1225:1232 arg1 Sp-1 1214:1217 O-GlcNAcylated Sp-1 1199:1217 O-GlcNAcylated Sp-1 1199:1217 In addition, membrane permeable non-O-GlcNAcylated Sp-1 did show transcriptional activity, while membrane permeable O-GlcNAcylated Sp-1 did not, suggesting O-GlcNAcylated Sp-1 is an inactive form in keratinocyte differentiation. 24802710 8 56 theme involucrin 935:944 arg1 terms 926:930 terms 926:930 terms of involucrin and loricrin promoter activities 926:977 Interestingly, transcriptional activity of Sp-1, in terms of involucrin and loricrin promoter activities, was markedly increased by overexpression of O-GlcNAcase (OGA). 24692660 7 0 theme transcription 939:951 arg1 regulation 920:929 regulation 920:929 regulation of gene transcription 920:951 Taken together, these results reveal a crosstalk between the LKB1-AMPK and the hexosamine biosynthesis (HBP)-OGT pathways, which coordinate together for the sensing of nutrient state and regulation of gene transcription. 24692660 7 0 theme transcription 939:951 arg1 sensing 890:896 the sensing 886:896 the sensing of nutrient state 886:914 Taken together, these results reveal a crosstalk between the LKB1-AMPK and the hexosamine biosynthesis (HBP)-OGT pathways, which coordinate together for the sensing of nutrient state and regulation of gene transcription. 24692660 7 1 theme hexosamine 812:821 arg1 HBP 837:839 HBP 837:839 HBP 837:839 Taken together, these results reveal a crosstalk between the LKB1-AMPK and the hexosamine biosynthesis (HBP)-OGT pathways, which coordinate together for the sensing of nutrient state and regulation of gene transcription. 24692660 7 1 theme hexosamine 812:821 arg1 biosynthesis 823:834 the hexosamine biosynthesis 808:834 the hexosamine biosynthesis (HBP)-OGT pathways 808:853 Taken together, these results reveal a crosstalk between the LKB1-AMPK and the hexosamine biosynthesis (HBP)-OGT pathways, which coordinate together for the sensing of nutrient state and regulation of gene transcription. 24692660 5 2 theme OGT-chromatin 551:563 arg1 association 565:575 OGT-chromatin association 551:575 OGT-chromatin association 551:575 Although this phosphorylation does not regulate the enzymatic activity of OGT, it inhibits OGT-chromatin association, histone O-GlcNAcylation and gene transcription. 24692660 5 3 theme histone 578:584 arg1 O-GlcNAcylation 586:600 histone O-GlcNAcylation 578:600 histone O-GlcNAcylation 578:600 Although this phosphorylation does not regulate the enzymatic activity of OGT, it inhibits OGT-chromatin association, histone O-GlcNAcylation and gene transcription. 24692660 3 4 theme protein 304:310 arg1 AMPK 320:323 AMPK 320:323 AMPK 320:323 Here we found that the energy-sensing adenosine-monophosphate-activated protein kinase (AMPK) could suppress histone H2B O-GlcNAcylation. 24692660 3 4 theme protein 304:310 arg1 kinase 312:317 energy-sensing adenosine-monophosphate-activated protein kinase 255:317 the energy-sensing adenosine-monophosphate-activated protein kinase (AMPK) 251:324 Here we found that the energy-sensing adenosine-monophosphate-activated protein kinase (AMPK) could suppress histone H2B O-GlcNAcylation. 24692660 7 5 theme gene 934:937 arg1 transcription 939:951 gene transcription 934:951 gene transcription 934:951 Taken together, these results reveal a crosstalk between the LKB1-AMPK and the hexosamine biosynthesis (HBP)-OGT pathways, which coordinate together for the sensing of nutrient state and regulation of gene transcription. 24692660 1 6 theme important 78:86 arg1 modification 107:118 an important post-translational modification 75:118 an important post-translational modification of chromatin during gene transcription 75:157 Histone H2B O-GlcNAcylation is an important post-translational modification of chromatin during gene transcription. 24692660 1 6 theme important 78:86 arg1 O-GlcNAcylation 56:70 Histone H2B O-GlcNAcylation 44:70 Histone H2B O-GlcNAcylation 44:70 Histone H2B O-GlcNAcylation is an important post-translational modification of chromatin during gene transcription. 24692660 3 7 theme energy-sensing 255:268 arg1 AMPK 320:323 AMPK 320:323 AMPK 320:323 Here we found that the energy-sensing adenosine-monophosphate-activated protein kinase (AMPK) could suppress histone H2B O-GlcNAcylation. 24692660 3 7 theme energy-sensing 255:268 arg1 kinase 312:317 energy-sensing adenosine-monophosphate-activated protein kinase 255:317 the energy-sensing adenosine-monophosphate-activated protein kinase (AMPK) 251:324 Here we found that the energy-sensing adenosine-monophosphate-activated protein kinase (AMPK) could suppress histone H2B O-GlcNAcylation. 24692660 1 8 theme post-translational 88:105 arg1 modification 107:118 an important post-translational modification 75:118 an important post-translational modification of chromatin during gene transcription 75:157 Histone H2B O-GlcNAcylation is an important post-translational modification of chromatin during gene transcription. 24692660 1 8 theme post-translational 88:105 arg1 O-GlcNAcylation 56:70 Histone H2B O-GlcNAcylation 44:70 Histone H2B O-GlcNAcylation 44:70 Histone H2B O-GlcNAcylation is an important post-translational modification of chromatin during gene transcription. 24692660 4 9 link O-linked 399:406 arg1 OGT 454:456 OGT 454:456 OGT 454:456 AMPK directly phosphorylates O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT). 24692660 4 9 link O-linked 399:406 arg1 transferase 441:451 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase 399:451 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) 399:457 AMPK directly phosphorylates O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT). 24692660 6 10 theme AMPK 692:695 arg1 activity 697:704 AMPK activity 692:704 AMPK activity 692:704 Conversely, OGT also O-GlcNAcylates AMPK and positively regulates AMPK activity, creating a feedback loop. 24692660 3 11 theme adenosine-monophosphate-activated 270:302 arg1 AMPK 320:323 AMPK 320:323 AMPK 320:323 Here we found that the energy-sensing adenosine-monophosphate-activated protein kinase (AMPK) could suppress histone H2B O-GlcNAcylation. 24692660 3 11 theme adenosine-monophosphate-activated 270:302 arg1 kinase 312:317 energy-sensing adenosine-monophosphate-activated protein kinase 255:317 the energy-sensing adenosine-monophosphate-activated protein kinase (AMPK) 251:324 Here we found that the energy-sensing adenosine-monophosphate-activated protein kinase (AMPK) could suppress histone H2B O-GlcNAcylation. 24692660 5 12 theme OGT 534:536 arg1 activity 522:529 the enzymatic activity 508:529 the enzymatic activity of OGT 508:536 Although this phosphorylation does not regulate the enzymatic activity of OGT, it inhibits OGT-chromatin association, histone O-GlcNAcylation and gene transcription. 24692660 0 13 theme H2B 23:25 arg1 O-GlcNAcylation 27:41 histone H2B O-GlcNAcylation 15:41 histone H2B O-GlcNAcylation 15:41 AMPK regulates histone H2B O-GlcNAcylation. 24692660 7 14 theme state 910:914 arg1 regulation 920:929 regulation 920:929 regulation of gene transcription 920:951 Taken together, these results reveal a crosstalk between the LKB1-AMPK and the hexosamine biosynthesis (HBP)-OGT pathways, which coordinate together for the sensing of nutrient state and regulation of gene transcription. 24692660 7 14 theme state 910:914 arg1 sensing 890:896 the sensing 886:896 the sensing of nutrient state 886:914 Taken together, these results reveal a crosstalk between the LKB1-AMPK and the hexosamine biosynthesis (HBP)-OGT pathways, which coordinate together for the sensing of nutrient state and regulation of gene transcription. 24692660 0 15 theme histone 15:21 arg1 O-GlcNAcylation 27:41 histone H2B O-GlcNAcylation 15:41 histone H2B O-GlcNAcylation 15:41 AMPK regulates histone H2B O-GlcNAcylation. 24692660 1 16 theme chromatin 123:131 arg1 modification 107:118 an important post-translational modification 75:118 an important post-translational modification of chromatin during gene transcription 75:157 Histone H2B O-GlcNAcylation is an important post-translational modification of chromatin during gene transcription. 24692660 1 16 theme chromatin 123:131 arg1 O-GlcNAcylation 56:70 Histone H2B O-GlcNAcylation 44:70 Histone H2B O-GlcNAcylation 44:70 Histone H2B O-GlcNAcylation is an important post-translational modification of chromatin during gene transcription. 24692660 7 17 theme nutrient 901:908 arg1 state 910:914 nutrient state 901:914 nutrient state 901:914 Taken together, these results reveal a crosstalk between the LKB1-AMPK and the hexosamine biosynthesis (HBP)-OGT pathways, which coordinate together for the sensing of nutrient state and regulation of gene transcription. 24692660 4 18 theme β-N-acetylglucosamine 408:428 arg1 OGT 454:456 OGT 454:456 OGT 454:456 AMPK directly phosphorylates O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT). 24692660 4 18 theme β-N-acetylglucosamine 408:428 arg1 transferase 441:451 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase 399:451 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) 399:457 AMPK directly phosphorylates O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT). 24692660 3 19 theme H2B 349:351 arg1 O-GlcNAcylation 353:367 histone H2B O-GlcNAcylation 341:367 histone H2B O-GlcNAcylation 341:367 Here we found that the energy-sensing adenosine-monophosphate-activated protein kinase (AMPK) could suppress histone H2B O-GlcNAcylation. 24692660 2 20 theme epigenetic 178:187 arg1 modification 189:200 this epigenetic modification 173:200 this epigenetic modification 173:200 However, how this epigenetic modification is regulated remains unclear. 24692660 4 21 theme O-linked 399:406 arg1 OGT 454:456 OGT 454:456 OGT 454:456 AMPK directly phosphorylates O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT). 24692660 4 21 theme O-linked 399:406 arg1 transferase 441:451 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase 399:451 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) 399:457 AMPK directly phosphorylates O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT). 24692660 7 22 theme -OGT 841:844 arg1 pathways 846:853 the hexosamine biosynthesis (HBP)-OGT pathways 808:853 the hexosamine biosynthesis (HBP)-OGT pathways 808:853 Taken together, these results reveal a crosstalk between the LKB1-AMPK and the hexosamine biosynthesis (HBP)-OGT pathways, which coordinate together for the sensing of nutrient state and regulation of gene transcription. 24692660 7 23 dep LKB1-AMPK 794:802 arg1 the 790:792 the 790:792 the 790:792 Taken together, these results reveal a crosstalk between the LKB1-AMPK and the hexosamine biosynthesis (HBP)-OGT pathways, which coordinate together for the sensing of nutrient state and regulation of gene transcription. 24692660 4 24 theme O-GlcNAc 431:438 arg1 OGT 454:456 OGT 454:456 OGT 454:456 AMPK directly phosphorylates O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT). 24692660 4 24 theme O-GlcNAc 431:438 arg1 transferase 441:451 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase 399:451 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) 399:457 AMPK directly phosphorylates O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT). 24692660 1 25 theme gene 140:143 arg1 transcription 145:157 gene transcription 140:157 gene transcription 140:157 Histone H2B O-GlcNAcylation is an important post-translational modification of chromatin during gene transcription. 24692660 5 26 theme enzymatic 512:520 arg1 activity 522:529 the enzymatic activity 508:529 the enzymatic activity of OGT 508:536 Although this phosphorylation does not regulate the enzymatic activity of OGT, it inhibits OGT-chromatin association, histone O-GlcNAcylation and gene transcription. 24692660 3 27 theme histone 341:347 arg1 H2B 349:351 histone H2B 341:351 histone H2B O-GlcNAcylation 341:367 Here we found that the energy-sensing adenosine-monophosphate-activated protein kinase (AMPK) could suppress histone H2B O-GlcNAcylation. 24692660 1 28 theme Histone 44:50 arg1 modification 107:118 an important post-translational modification 75:118 an important post-translational modification of chromatin during gene transcription 75:157 Histone H2B O-GlcNAcylation is an important post-translational modification of chromatin during gene transcription. 24692660 1 28 theme Histone 44:50 arg1 O-GlcNAcylation 56:70 Histone H2B O-GlcNAcylation 44:70 Histone H2B O-GlcNAcylation 44:70 Histone H2B O-GlcNAcylation is an important post-translational modification of chromatin during gene transcription. 24692660 7 29 theme biosynthesis 823:834 arg1 pathways 846:853 the hexosamine biosynthesis (HBP)-OGT pathways 808:853 the hexosamine biosynthesis (HBP)-OGT pathways 808:853 Taken together, these results reveal a crosstalk between the LKB1-AMPK and the hexosamine biosynthesis (HBP)-OGT pathways, which coordinate together for the sensing of nutrient state and regulation of gene transcription. 24692660 1 30 theme H2B 52:54 arg1 modification 107:118 an important post-translational modification 75:118 an important post-translational modification of chromatin during gene transcription 75:157 Histone H2B O-GlcNAcylation is an important post-translational modification of chromatin during gene transcription. 24692660 1 30 theme H2B 52:54 arg1 O-GlcNAcylation 56:70 Histone H2B O-GlcNAcylation 44:70 Histone H2B O-GlcNAcylation 44:70 Histone H2B O-GlcNAcylation is an important post-translational modification of chromatin during gene transcription. 24692660 5 31 theme gene 606:609 arg1 transcription 611:623 gene transcription 606:623 gene transcription 606:623 Although this phosphorylation does not regulate the enzymatic activity of OGT, it inhibits OGT-chromatin association, histone O-GlcNAcylation and gene transcription. 24692660 6 32 theme feedback 718:725 arg1 loop 727:730 a feedback loop 716:730 a feedback loop 716:730 Conversely, OGT also O-GlcNAcylates AMPK and positively regulates AMPK activity, creating a feedback loop. 24576160 2 0 theme CHO 375:377 arg1 cells 379:383 CHO cells 375:383 CHO cells 375:383 Opioid binding affinities of the O-linked glycopeptides (mono- or disaccharides) and unglycosylated peptide controls were measured in human receptors expressed in CHO cells. 24576160 0 1 theme related 84:90 arg1 glycopeptides 70:82 glycopeptides 70:82 glycopeptides related to β-endorphin 70:105 Can amphipathic helices influence the CNS antinociceptive activity of glycopeptides related to β-endorphin? 24576160 6 2 theme i.v. 763:766 arg1 administration 768:781 i.v. administration 763:781 i.v. administration 763:781 Glycosylation was essential for activity after i.v. administration. 24576160 5 3 theme Circular 609:616 arg1 dichroism 618:626 Circular dichroism 609:626 Circular dichroism 609:626 Circular dichroism and NMR indicated the degree of helicity in H2O, aqueous trifluoroethanol, or micelles. 24576160 2 4 theme unglycosylated 297:310 arg1 controls 320:327 unglycosylated peptide controls 297:327 unglycosylated peptide controls 297:327 Opioid binding affinities of the O-linked glycopeptides (mono- or disaccharides) and unglycosylated peptide controls were measured in human receptors expressed in CHO cells. 24576160 2 5 theme peptide 312:318 arg1 controls 320:327 unglycosylated peptide controls 297:327 unglycosylated peptide controls 297:327 Opioid binding affinities of the O-linked glycopeptides (mono- or disaccharides) and unglycosylated peptide controls were measured in human receptors expressed in CHO cells. 24576160 2 6 gly unglycosylated 297:310 arg1 controls 320:327 unglycosylated peptide controls 297:327 unglycosylated peptide controls 297:327 Opioid binding affinities of the O-linked glycopeptides (mono- or disaccharides) and unglycosylated peptide controls were measured in human receptors expressed in CHO cells. 24576160 7 7 from degree 1086:1091 arg1 micelles 1108:1115 micelles 1108:1115 micelles 1108:1115 It was possible to manipulate the degree of helicity by the alteration of only two amino acid residues in the helical address region of the β-endorphin analogues without destroying μ-, δ-, or κ-agonism, but the antinociceptive activity after i.v. administration could not be directly correlated to the degree of helicity in micelles. 24576160 3 8 dep range 471:475 arg1 K 488:488 2.2-35 nM K 478:488 2.2-35 nM K(i)'s 478:493 All were pan-agonists, binding to μ-, δ-, or κ-opioid receptors in the low nanomolar range (2.2-35 nM K(i)'s). 24576160 3 8 dep range 471:475 arg1 i 490:490 i 490:490 i 490:490 All were pan-agonists, binding to μ-, δ-, or κ-opioid receptors in the low nanomolar range (2.2-35 nM K(i)'s). 24576160 0 9 gly glycopeptides 70:82 arg2 glycopeptides 70:82 glycopeptides 70:82 glycopeptides related to β-endorphin 70:105 Can amphipathic helices influence the CNS antinociceptive activity of glycopeptides related to β-endorphin? 24576160 5 10 from degree 650:655 arg1 H2O 672:674 H2O 672:674 H2O 672:674 Circular dichroism and NMR indicated the degree of helicity in H2O, aqueous trifluoroethanol, or micelles. 24576160 5 10 from degree 650:655 arg1 trifluoroethanol 685:700 aqueous trifluoroethanol 677:700 aqueous trifluoroethanol 677:700 Circular dichroism and NMR indicated the degree of helicity in H2O, aqueous trifluoroethanol, or micelles. 24576160 5 10 from degree 650:655 arg1 micelles 706:713 micelles 706:713 micelles 706:713 Circular dichroism and NMR indicated the degree of helicity in H2O, aqueous trifluoroethanol, or micelles. 24576160 7 11 from region 910:915 arg1 alteration 844:853 the alteration 840:853 the alteration of only two amino acid residues in the helical address region of the β-endorphin analogues 840:944 It was possible to manipulate the degree of helicity by the alteration of only two amino acid residues in the helical address region of the β-endorphin analogues without destroying μ-, δ-, or κ-agonism, but the antinociceptive activity after i.v. administration could not be directly correlated to the degree of helicity in micelles. 24576160 5 12 theme aqueous 677:683 arg1 trifluoroethanol 685:700 aqueous trifluoroethanol 677:700 aqueous trifluoroethanol 677:700 Circular dichroism and NMR indicated the degree of helicity in H2O, aqueous trifluoroethanol, or micelles. 24576160 3 13 theme μ- 420:421 arg1 receptors 440:448 μ-, δ-, or κ-opioid receptors 420:448 μ-, δ-, or κ-opioid receptors in the low nanomolar range (2.2-35 nM K(i)'s) 420:494 All were pan-agonists, binding to μ-, δ-, or κ-opioid receptors in the low nanomolar range (2.2-35 nM K(i)'s). 24576160 7 14 theme acid 873:876 arg1 residues 878:885 only two amino acid residues 858:885 only two amino acid residues in the helical address region of the β-endorphin analogues 858:944 It was possible to manipulate the degree of helicity by the alteration of only two amino acid residues in the helical address region of the β-endorphin analogues without destroying μ-, δ-, or κ-agonism, but the antinociceptive activity after i.v. administration could not be directly correlated to the degree of helicity in micelles. 24576160 2 15 dep glycopeptides 254:266 arg1 the 241:243 the 241:243 the 241:243 Opioid binding affinities of the O-linked glycopeptides (mono- or disaccharides) and unglycosylated peptide controls were measured in human receptors expressed in CHO cells. 24576160 2 15 dep glycopeptides 254:266 arg1 disaccharides 278:290 disaccharides 278:290 disaccharides 278:290 Opioid binding affinities of the O-linked glycopeptides (mono- or disaccharides) and unglycosylated peptide controls were measured in human receptors expressed in CHO cells. 24576160 2 15 dep glycopeptides 254:266 arg1 mono- 269:273 mono- 269:273 mono- 269:273 Opioid binding affinities of the O-linked glycopeptides (mono- or disaccharides) and unglycosylated peptide controls were measured in human receptors expressed in CHO cells. 24576160 2 15 dep glycopeptides 254:266 arg1 glycopeptides 254:266 O-linked glycopeptides 245:266 O-linked glycopeptides (mono- or disaccharides) 245:291 Opioid binding affinities of the O-linked glycopeptides (mono- or disaccharides) and unglycosylated peptide controls were measured in human receptors expressed in CHO cells. 24576160 0 16 theme amphipathic 4:14 arg1 helices 16:22 amphipathic helices 4:22 amphipathic helices 4:22 Can amphipathic helices influence the CNS antinociceptive activity of glycopeptides related to β-endorphin? 24576160 7 17 theme antinociceptive 995:1009 arg1 activity 1011:1018 the antinociceptive activity 991:1018 the antinociceptive activity after i.v. administration 991:1044 It was possible to manipulate the degree of helicity by the alteration of only two amino acid residues in the helical address region of the β-endorphin analogues without destroying μ-, δ-, or κ-agonism, but the antinociceptive activity after i.v. administration could not be directly correlated to the degree of helicity in micelles. 24576160 7 18 theme residues 878:885 arg1 alteration 844:853 the alteration 840:853 the alteration of only two amino acid residues in the helical address region of the β-endorphin analogues 840:944 It was possible to manipulate the degree of helicity by the alteration of only two amino acid residues in the helical address region of the β-endorphin analogues without destroying μ-, δ-, or κ-agonism, but the antinociceptive activity after i.v. administration could not be directly correlated to the degree of helicity in micelles. 24576160 3 19 theme δ- 424:425 arg1 receptors 440:448 μ-, δ-, or κ-opioid receptors 420:448 μ-, δ-, or κ-opioid receptors in the low nanomolar range (2.2-35 nM K(i)'s) 420:494 All were pan-agonists, binding to μ-, δ-, or κ-opioid receptors in the low nanomolar range (2.2-35 nM K(i)'s). 24576160 4 20 theme glycoside 501:509 arg1 moiety 511:516 The glycoside moiety 497:516 The glycoside moiety 497:516 The glycoside moiety was required for intravenous (i.v.) but not for intracerebroventricular (i.c.v.) activity. 24576160 7 21 from alteration 844:853 arg1 region 910:915 the helical address region 890:915 the helical address region of the β-endorphin analogues 890:944 It was possible to manipulate the degree of helicity by the alteration of only two amino acid residues in the helical address region of the β-endorphin analogues without destroying μ-, δ-, or κ-agonism, but the antinociceptive activity after i.v. administration could not be directly correlated to the degree of helicity in micelles. 24576160 7 22 dep region 910:915 arg1 address 902:908 address 902:908 address 902:908 It was possible to manipulate the degree of helicity by the alteration of only two amino acid residues in the helical address region of the β-endorphin analogues without destroying μ-, δ-, or κ-agonism, but the antinociceptive activity after i.v. administration could not be directly correlated to the degree of helicity in micelles. 24576160 2 23 gly glycopeptides 254:266 arg2 disaccharides 278:290 disaccharides 278:290 disaccharides 278:290 Opioid binding affinities of the O-linked glycopeptides (mono- or disaccharides) and unglycosylated peptide controls were measured in human receptors expressed in CHO cells. 24576160 2 23 gly glycopeptides 254:266 arg2 mono- 269:273 mono- 269:273 mono- 269:273 Opioid binding affinities of the O-linked glycopeptides (mono- or disaccharides) and unglycosylated peptide controls were measured in human receptors expressed in CHO cells. 24576160 2 23 gly glycopeptides 254:266 arg2 glycopeptides 254:266 O-linked glycopeptides 245:266 O-linked glycopeptides (mono- or disaccharides) 245:291 Opioid binding affinities of the O-linked glycopeptides (mono- or disaccharides) and unglycosylated peptide controls were measured in human receptors expressed in CHO cells. 24576160 7 24 theme amino 867:871 arg1 residues 878:885 only two amino acid residues 858:885 only two amino acid residues in the helical address region of the β-endorphin analogues 858:944 It was possible to manipulate the degree of helicity by the alteration of only two amino acid residues in the helical address region of the β-endorphin analogues without destroying μ-, δ-, or κ-agonism, but the antinociceptive activity after i.v. administration could not be directly correlated to the degree of helicity in micelles. 24576160 2 25 theme controls 320:327 arg1 affinities 227:236 Opioid binding affinities 212:236 Opioid binding affinities of the O-linked glycopeptides (mono- or disaccharides) and unglycosylated peptide controls 212:327 Opioid binding affinities of the O-linked glycopeptides (mono- or disaccharides) and unglycosylated peptide controls were measured in human receptors expressed in CHO cells. 24576160 7 26 theme helical 894:900 arg1 region 910:915 the helical address region 890:915 the helical address region of the β-endorphin analogues 890:944 It was possible to manipulate the degree of helicity by the alteration of only two amino acid residues in the helical address region of the β-endorphin analogues without destroying μ-, δ-, or κ-agonism, but the antinociceptive activity after i.v. administration could not be directly correlated to the degree of helicity in micelles. 24576160 4 27 theme intracerebroventricular 566:588 arg1 activity 599:606 intracerebroventricular (i.c.v.) activity 566:606 intracerebroventricular (i.c.v.) activity 566:606 The glycoside moiety was required for intravenous (i.v.) but not for intracerebroventricular (i.c.v.) activity. 24576160 1 28 theme β-endorphin 121:131 arg1 analogues 133:141 Glycosylated β-endorphin analogues 108:141 Glycosylated β-endorphin analogues of various amphipathicity 108:167 Glycosylated β-endorphin analogues of various amphipathicity were studied in vitro and in vivo in mice. 24576160 3 29 theme low 457:459 arg1 range 471:475 the low nanomolar range 453:475 the low nanomolar range (2.2-35 nM K(i)'s) 453:494 All were pan-agonists, binding to μ-, δ-, or κ-opioid receptors in the low nanomolar range (2.2-35 nM K(i)'s). 24576160 0 30 theme CNS 38:40 arg1 activity 58:65 the CNS antinociceptive activity 34:65 the CNS antinociceptive activity of glycopeptides related to β-endorphin 34:105 Can amphipathic helices influence the CNS antinociceptive activity of glycopeptides related to β-endorphin? 24576160 2 31 theme O-linked 245:252 arg1 disaccharides 278:290 disaccharides 278:290 disaccharides 278:290 Opioid binding affinities of the O-linked glycopeptides (mono- or disaccharides) and unglycosylated peptide controls were measured in human receptors expressed in CHO cells. 24576160 2 31 theme O-linked 245:252 arg1 mono- 269:273 mono- 269:273 mono- 269:273 Opioid binding affinities of the O-linked glycopeptides (mono- or disaccharides) and unglycosylated peptide controls were measured in human receptors expressed in CHO cells. 24576160 2 31 theme O-linked 245:252 arg1 glycopeptides 254:266 O-linked glycopeptides 245:266 O-linked glycopeptides (mono- or disaccharides) 245:291 Opioid binding affinities of the O-linked glycopeptides (mono- or disaccharides) and unglycosylated peptide controls were measured in human receptors expressed in CHO cells. 24576160 5 32 theme helicity 660:667 arg1 degree 650:655 the degree 646:655 the degree of helicity in H2O, aqueous trifluoroethanol, or micelles 646:713 Circular dichroism and NMR indicated the degree of helicity in H2O, aqueous trifluoroethanol, or micelles. 24576160 3 33 from receptors 440:448 arg1 range 471:475 the low nanomolar range 453:475 the low nanomolar range (2.2-35 nM K(i)'s) 453:494 All were pan-agonists, binding to μ-, δ-, or κ-opioid receptors in the low nanomolar range (2.2-35 nM K(i)'s). 24576160 3 34 theme nM 485:486 arg1 K 488:488 2.2-35 nM K 478:488 2.2-35 nM K(i)'s 478:493 All were pan-agonists, binding to μ-, δ-, or κ-opioid receptors in the low nanomolar range (2.2-35 nM K(i)'s). 24576160 3 34 theme nM 485:486 arg1 i 490:490 i 490:490 i 490:490 All were pan-agonists, binding to μ-, δ-, or κ-opioid receptors in the low nanomolar range (2.2-35 nM K(i)'s). 24576160 4 35 dep intracerebroventricular 566:588 arg1 i.c.v. 591:596 i.c.v. 591:596 i.c.v. 591:596 The glycoside moiety was required for intravenous (i.v.) but not for intracerebroventricular (i.c.v.) activity. 24576160 0 36 theme antinociceptive 42:56 arg1 activity 58:65 the CNS antinociceptive activity 34:65 the CNS antinociceptive activity of glycopeptides related to β-endorphin 34:105 Can amphipathic helices influence the CNS antinociceptive activity of glycopeptides related to β-endorphin? 24576160 3 37 theme nanomolar 461:469 arg1 range 471:475 the low nanomolar range 453:475 the low nanomolar range (2.2-35 nM K(i)'s) 453:494 All were pan-agonists, binding to μ-, δ-, or κ-opioid receptors in the low nanomolar range (2.2-35 nM K(i)'s). 24576160 2 38 theme binding 219:225 arg1 affinities 227:236 Opioid binding affinities 212:236 Opioid binding affinities of the O-linked glycopeptides (mono- or disaccharides) and unglycosylated peptide controls 212:327 Opioid binding affinities of the O-linked glycopeptides (mono- or disaccharides) and unglycosylated peptide controls were measured in human receptors expressed in CHO cells. 24576160 7 39 theme i.v. 1026:1029 arg1 administration 1031:1044 i.v. administration 1026:1044 i.v. administration 1026:1044 It was possible to manipulate the degree of helicity by the alteration of only two amino acid residues in the helical address region of the β-endorphin analogues without destroying μ-, δ-, or κ-agonism, but the antinociceptive activity after i.v. administration could not be directly correlated to the degree of helicity in micelles. 24576160 7 40 theme analogues 936:944 arg1 region 910:915 the helical address region 890:915 the helical address region of the β-endorphin analogues 890:944 It was possible to manipulate the degree of helicity by the alteration of only two amino acid residues in the helical address region of the β-endorphin analogues without destroying μ-, δ-, or κ-agonism, but the antinociceptive activity after i.v. administration could not be directly correlated to the degree of helicity in micelles. 24576160 3 41 theme 2.2-35 478:483 arg1 nM 485:486 nM 485:486 nM 485:486 All were pan-agonists, binding to μ-, δ-, or κ-opioid receptors in the low nanomolar range (2.2-35 nM K(i)'s). 24576160 7 42 from residues 878:885 arg1 region 910:915 the helical address region 890:915 the helical address region of the β-endorphin analogues 890:944 It was possible to manipulate the degree of helicity by the alteration of only two amino acid residues in the helical address region of the β-endorphin analogues without destroying μ-, δ-, or κ-agonism, but the antinociceptive activity after i.v. administration could not be directly correlated to the degree of helicity in micelles. 24576160 2 43 theme Opioid 212:217 arg1 affinities 227:236 Opioid binding affinities 212:236 Opioid binding affinities of the O-linked glycopeptides (mono- or disaccharides) and unglycosylated peptide controls 212:327 Opioid binding affinities of the O-linked glycopeptides (mono- or disaccharides) and unglycosylated peptide controls were measured in human receptors expressed in CHO cells. 24576160 1 44 theme various 146:152 arg1 amphipathicity 154:167 various amphipathicity 146:167 various amphipathicity 146:167 Glycosylated β-endorphin analogues of various amphipathicity were studied in vitro and in vivo in mice. 24576160 1 45 theme Glycosylated 108:119 arg1 analogues 133:141 Glycosylated β-endorphin analogues 108:141 Glycosylated β-endorphin analogues of various amphipathicity 108:167 Glycosylated β-endorphin analogues of various amphipathicity were studied in vitro and in vivo in mice. 24576160 1 46 theme amphipathicity 154:167 arg1 analogues 133:141 Glycosylated β-endorphin analogues 108:141 Glycosylated β-endorphin analogues of various amphipathicity 108:167 Glycosylated β-endorphin analogues of various amphipathicity were studied in vitro and in vivo in mice. 24576160 2 47 theme human 346:350 arg1 receptors 352:360 human receptors 346:360 human receptors expressed in CHO cells 346:383 Opioid binding affinities of the O-linked glycopeptides (mono- or disaccharides) and unglycosylated peptide controls were measured in human receptors expressed in CHO cells. 24576160 0 48 theme glycopeptides 70:82 arg1 activity 58:65 the CNS antinociceptive activity 34:65 the CNS antinociceptive activity of glycopeptides related to β-endorphin 34:105 Can amphipathic helices influence the CNS antinociceptive activity of glycopeptides related to β-endorphin? 24576160 7 49 theme β-endorphin 924:934 arg1 analogues 936:944 the β-endorphin analogues 920:944 the β-endorphin analogues 920:944 It was possible to manipulate the degree of helicity by the alteration of only two amino acid residues in the helical address region of the β-endorphin analogues without destroying μ-, δ-, or κ-agonism, but the antinociceptive activity after i.v. administration could not be directly correlated to the degree of helicity in micelles. 24576160 3 50 theme κ-opioid 431:438 arg1 receptors 440:448 μ-, δ-, or κ-opioid receptors 420:448 μ-, δ-, or κ-opioid receptors in the low nanomolar range (2.2-35 nM K(i)'s) 420:494 All were pan-agonists, binding to μ-, δ-, or κ-opioid receptors in the low nanomolar range (2.2-35 nM K(i)'s). 24576160 2 51 link O-linked 245:252 arg1 disaccharides 278:290 disaccharides 278:290 disaccharides 278:290 Opioid binding affinities of the O-linked glycopeptides (mono- or disaccharides) and unglycosylated peptide controls were measured in human receptors expressed in CHO cells. 24576160 2 51 link O-linked 245:252 arg1 mono- 269:273 mono- 269:273 mono- 269:273 Opioid binding affinities of the O-linked glycopeptides (mono- or disaccharides) and unglycosylated peptide controls were measured in human receptors expressed in CHO cells. 24576160 2 51 link O-linked 245:252 arg1 glycopeptides 254:266 O-linked glycopeptides 245:266 O-linked glycopeptides (mono- or disaccharides) 245:291 Opioid binding affinities of the O-linked glycopeptides (mono- or disaccharides) and unglycosylated peptide controls were measured in human receptors expressed in CHO cells. 24576160 2 52 theme glycopeptides 254:266 arg1 affinities 227:236 Opioid binding affinities 212:236 Opioid binding affinities of the O-linked glycopeptides (mono- or disaccharides) and unglycosylated peptide controls 212:327 Opioid binding affinities of the O-linked glycopeptides (mono- or disaccharides) and unglycosylated peptide controls were measured in human receptors expressed in CHO cells. 24576160 7 53 theme helicity 1096:1103 arg1 degree 1086:1091 the degree 1082:1091 the degree of helicity in micelles 1082:1115 It was possible to manipulate the degree of helicity by the alteration of only two amino acid residues in the helical address region of the β-endorphin analogues without destroying μ-, δ-, or κ-agonism, but the antinociceptive activity after i.v. administration could not be directly correlated to the degree of helicity in micelles. 24576160 7 54 theme helicity 828:835 arg1 degree 818:823 the degree 814:823 the degree of helicity 814:835 It was possible to manipulate the degree of helicity by the alteration of only two amino acid residues in the helical address region of the β-endorphin analogues without destroying μ-, δ-, or κ-agonism, but the antinociceptive activity after i.v. administration could not be directly correlated to the degree of helicity in micelles. 26674417 8 0 theme Hox 1158:1160 arg1 genes 1162:1166 Hox genes 1158:1166 Hox genes 1158:1166 However, the hypomorphic OGT mutant-rescued progeny do not produce F2 adults, because a set of Hox genes is de-repressed in F2 embryos, resulting in homeotic phenotypes. 26674417 9 1 theme late 1280:1283 arg1 stages 1291:1296 late pupal stages 1280:1296 late pupal stages 1280:1296 Thus, OGT catalytic activity is required up to late pupal stages, while further development proceeds with severely reduced OGT activity. 26674417 8 2 theme genes 1162:1166 arg1 de-repressed 1171:1182 de-repressed 1171:1182 de-repressed 1171:1182 However, the hypomorphic OGT mutant-rescued progeny do not produce F2 adults, because a set of Hox genes is de-repressed in F2 embryos, resulting in homeotic phenotypes. 26674417 8 2 theme genes 1162:1166 arg1 set 1151:1153 a set 1149:1153 a set of Hox genes 1149:1166 However, the hypomorphic OGT mutant-rescued progeny do not produce F2 adults, because a set of Hox genes is de-repressed in F2 embryos, resulting in homeotic phenotypes. 26674417 8 2 theme genes 1162:1166 arg1 genes 1162:1166 Hox genes 1158:1166 Hox genes 1158:1166 However, the hypomorphic OGT mutant-rescued progeny do not produce F2 adults, because a set of Hox genes is de-repressed in F2 embryos, resulting in homeotic phenotypes. 26674417 1 3 theme cellular 267:274 arg1 functions 276:284 diverse cellular functions 259:284 diverse cellular functions 259:284 Post-translational modification of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc) catalysed by O-GlcNAc transferase (OGT) has been linked to regulation of diverse cellular functions. 26674417 5 4 theme OGT 791:793 arg1 activity-dependent 795:812 OGT activity-dependent 791:812 OGT activity-dependent 791:812 Here we use a genetic approach to demonstrate that post-pupal Drosophila development can proceed with negligible OGT catalysis, while early embryonic development is OGT activity-dependent. 26674417 6 5 theme mutants 930:936 arg1 design 908:913 the rational design 895:913 the rational design of DmOGT point mutants 895:936 Structural and enzymatic comparison between human OGT (hOGT) and DmOGT informed the rational design of DmOGT point mutants with a range of reduced catalytic activities. 26674417 6 6 theme human 859:863 arg1 hOGT 870:873 hOGT 870:873 hOGT 870:873 Structural and enzymatic comparison between human OGT (hOGT) and DmOGT informed the rational design of DmOGT point mutants with a range of reduced catalytic activities. 26674417 6 6 theme human 859:863 arg1 OGT 865:867 human OGT 859:867 human OGT (hOGT) 859:874 Structural and enzymatic comparison between human OGT (hOGT) and DmOGT informed the rational design of DmOGT point mutants with a range of reduced catalytic activities. 26674417 9 7 theme catalytic 1243:1251 arg1 activity 1253:1260 OGT catalytic activity 1239:1260 OGT catalytic activity 1239:1260 Thus, OGT catalytic activity is required up to late pupal stages, while further development proceeds with severely reduced OGT activity. 26674417 1 8 theme functions 276:284 arg1 regulation 245:254 regulation 245:254 regulation of diverse cellular functions 245:284 Post-translational modification of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc) catalysed by O-GlcNAc transferase (OGT) has been linked to regulation of diverse cellular functions. 26674417 6 9 theme point 924:928 arg1 mutants 930:936 DmOGT point mutants 918:936 DmOGT point mutants 918:936 Structural and enzymatic comparison between human OGT (hOGT) and DmOGT informed the rational design of DmOGT point mutants with a range of reduced catalytic activities. 26674417 2 10 theme glycosyltransferase 314:332 arg1 domain 344:349 a C-terminal glycosyltransferase catalytic domain 301:349 a C-terminal glycosyltransferase catalytic domain 301:349 OGT possesses a C-terminal glycosyltransferase catalytic domain and N-terminal tetratricopeptide repeats that are implicated in protein-protein interactions. 26674417 2 11 theme catalytic 334:342 arg1 domain 344:349 a C-terminal glycosyltransferase catalytic domain 301:349 a C-terminal glycosyltransferase catalytic domain 301:349 OGT possesses a C-terminal glycosyltransferase catalytic domain and N-terminal tetratricopeptide repeats that are implicated in protein-protein interactions. 26674417 8 12 theme OGT 1088:1090 arg1 progeny 1107:1113 the hypomorphic OGT mutant-rescued progeny 1072:1113 the hypomorphic OGT mutant-rescued progeny 1072:1113 However, the hypomorphic OGT mutant-rescued progeny do not produce F2 adults, because a set of Hox genes is de-repressed in F2 embryos, resulting in homeotic phenotypes. 26674417 6 13 theme DmOGT 918:922 arg1 mutants 930:936 DmOGT point mutants 918:936 DmOGT point mutants 918:936 Structural and enzymatic comparison between human OGT (hOGT) and DmOGT informed the rational design of DmOGT point mutants with a range of reduced catalytic activities. 26674417 2 14 theme C-terminal 303:312 arg1 domain 344:349 a C-terminal glycosyltransferase catalytic domain 301:349 a C-terminal glycosyltransferase catalytic domain 301:349 OGT possesses a C-terminal glycosyltransferase catalytic domain and N-terminal tetratricopeptide repeats that are implicated in protein-protein interactions. 26674417 8 15 theme hypomorphic 1076:1086 arg1 progeny 1107:1113 the hypomorphic OGT mutant-rescued progeny 1072:1113 the hypomorphic OGT mutant-rescued progeny 1072:1113 However, the hypomorphic OGT mutant-rescued progeny do not produce F2 adults, because a set of Hox genes is de-repressed in F2 embryos, resulting in homeotic phenotypes. 26674417 6 16 theme enzymatic 830:838 arg1 comparison 840:849 Structural and enzymatic comparison 815:849 Structural and enzymatic comparison between human OGT (hOGT) and DmOGT 815:884 Structural and enzymatic comparison between human OGT (hOGT) and DmOGT informed the rational design of DmOGT point mutants with a range of reduced catalytic activities. 26674417 1 17 theme O-GlcNAc 199:206 arg1 OGT 221:223 OGT 221:223 OGT 221:223 Post-translational modification of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc) catalysed by O-GlcNAc transferase (OGT) has been linked to regulation of diverse cellular functions. 26674417 1 17 theme O-GlcNAc 199:206 arg1 transferase 208:218 O-GlcNAc transferase 199:218 O-GlcNAc transferase (OGT) 199:224 Post-translational modification of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc) catalysed by O-GlcNAc transferase (OGT) has been linked to regulation of diverse cellular functions. 26674417 5 18 theme early 760:764 arg1 development 776:786 early embryonic development 760:786 early embryonic development 760:786 Here we use a genetic approach to demonstrate that post-pupal Drosophila development can proceed with negligible OGT catalysis, while early embryonic development is OGT activity-dependent. 26674417 9 19 theme further 1305:1311 arg1 development 1313:1323 further development 1305:1323 further development 1305:1323 Thus, OGT catalytic activity is required up to late pupal stages, while further development proceeds with severely reduced OGT activity. 26674417 1 20 theme Post-translational 83:100 arg1 modification 102:113 Post-translational modification 83:113 Post-translational modification of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc) catalysed by O-GlcNAc transferase (OGT) 83:224 Post-translational modification of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc) catalysed by O-GlcNAc transferase (OGT) has been linked to regulation of diverse cellular functions. 26674417 3 21 theme combs 492:496 arg1 mutants 505:511 mutants 505:511 mutants 505:511 Drosophila OGT (DmOGT) is encoded by super sex combs (sxc), mutants of which are pupal lethal. 26674417 6 22 theme rational 899:906 arg1 design 908:913 the rational design 895:913 the rational design of DmOGT point mutants 895:936 Structural and enzymatic comparison between human OGT (hOGT) and DmOGT informed the rational design of DmOGT point mutants with a range of reduced catalytic activities. 26674417 8 23 theme mutant-rescued 1092:1105 arg1 progeny 1107:1113 the hypomorphic OGT mutant-rescued progeny 1072:1113 the hypomorphic OGT mutant-rescued progeny 1072:1113 However, the hypomorphic OGT mutant-rescued progeny do not produce F2 adults, because a set of Hox genes is de-repressed in F2 embryos, resulting in homeotic phenotypes. 26674417 6 24 theme Structural 815:824 arg1 comparison 840:849 Structural and enzymatic comparison 815:849 Structural and enzymatic comparison between human OGT (hOGT) and DmOGT 815:884 Structural and enzymatic comparison between human OGT (hOGT) and DmOGT informed the rational design of DmOGT point mutants with a range of reduced catalytic activities. 26674417 2 25 theme N-terminal 355:364 arg1 repeats 384:390 N-terminal tetratricopeptide repeats 355:390 N-terminal tetratricopeptide repeats 355:390 OGT possesses a C-terminal glycosyltransferase catalytic domain and N-terminal tetratricopeptide repeats that are implicated in protein-protein interactions. 26674417 8 26 theme F2 1130:1131 arg1 adults 1133:1138 F2 adults 1130:1138 F2 adults 1130:1138 However, the hypomorphic OGT mutant-rescued progeny do not produce F2 adults, because a set of Hox genes is de-repressed in F2 embryos, resulting in homeotic phenotypes. 26674417 0 27 theme Dual 0:3 arg1 functionality 5:17 Dual functionality 0:17 Dual functionality of O-GlcNAc transferase 0:41 Dual functionality of O-GlcNAc transferase is required for Drosophila development. 26674417 2 28 contain possesses 291:299 arg2 domain 344:349 a C-terminal glycosyltransferase catalytic domain 301:349 a C-terminal glycosyltransferase catalytic domain 301:349 OGT possesses a C-terminal glycosyltransferase catalytic domain and N-terminal tetratricopeptide repeats that are implicated in protein-protein interactions. 26674417 2 28 contain possesses 291:299 arg2 repeats 384:390 N-terminal tetratricopeptide repeats 355:390 N-terminal tetratricopeptide repeats 355:390 OGT possesses a C-terminal glycosyltransferase catalytic domain and N-terminal tetratricopeptide repeats that are implicated in protein-protein interactions. 26674417 2 28 contain possesses 291:299 arg1 OGT 287:289 OGT 287:289 OGT 287:289 OGT possesses a C-terminal glycosyltransferase catalytic domain and N-terminal tetratricopeptide repeats that are implicated in protein-protein interactions. 26674417 5 29 theme genetic 640:646 arg1 approach 648:655 a genetic approach 638:655 a genetic approach to demonstrate that post-pupal Drosophila development can proceed with negligible OGT catalysis, while early embryonic development is OGT activity-dependent 638:812 Here we use a genetic approach to demonstrate that post-pupal Drosophila development can proceed with negligible OGT catalysis, while early embryonic development is OGT activity-dependent. 26674417 3 30 theme super 482:486 arg1 sxc 499:501 sxc 499:501 sxc 499:501 Drosophila OGT (DmOGT) is encoded by super sex combs (sxc), mutants of which are pupal lethal. 26674417 3 30 theme super 482:486 arg1 combs 492:496 super sex combs 482:496 super sex combs (sxc) 482:502 Drosophila OGT (DmOGT) is encoded by super sex combs (sxc), mutants of which are pupal lethal. 26674417 1 31 with modification 102:113 arg1 N-acetylglucosamine 155:173 O-linked N-acetylglucosamine 146:173 O-linked N-acetylglucosamine (O-GlcNAc) catalysed by O-GlcNAc transferase (OGT) 146:224 Post-translational modification of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc) catalysed by O-GlcNAc transferase (OGT) has been linked to regulation of diverse cellular functions. 26674417 1 31 with modification 102:113 arg1 O-GlcNAc 176:183 O-GlcNAc 176:183 O-GlcNAc 176:183 Post-translational modification of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc) catalysed by O-GlcNAc transferase (OGT) has been linked to regulation of diverse cellular functions. 26674417 9 32 dep stages 1291:1296 arg1 up 1274:1275 up 1274:1275 up 1274:1275 Thus, OGT catalytic activity is required up to late pupal stages, while further development proceeds with severely reduced OGT activity. 26674417 1 33 theme intracellular 118:130 arg1 proteins 132:139 intracellular proteins 118:139 intracellular proteins 118:139 Post-translational modification of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc) catalysed by O-GlcNAc transferase (OGT) has been linked to regulation of diverse cellular functions. 26674417 3 34 theme Drosophila 445:454 arg1 OGT 456:458 Drosophila OGT 445:458 Drosophila OGT (DmOGT) 445:466 Drosophila OGT (DmOGT) is encoded by super sex combs (sxc), mutants of which are pupal lethal. 26674417 3 34 theme Drosophila 445:454 arg1 DmOGT 461:465 DmOGT 461:465 DmOGT 461:465 Drosophila OGT (DmOGT) is encoded by super sex combs (sxc), mutants of which are pupal lethal. 26674417 1 35 theme proteins 132:139 arg1 modification 102:113 Post-translational modification 83:113 Post-translational modification of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc) catalysed by O-GlcNAc transferase (OGT) 83:224 Post-translational modification of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc) catalysed by O-GlcNAc transferase (OGT) has been linked to regulation of diverse cellular functions. 26674417 8 36 theme homeotic 1212:1219 arg1 phenotypes 1221:1230 homeotic phenotypes 1212:1230 homeotic phenotypes 1212:1230 However, the hypomorphic OGT mutant-rescued progeny do not produce F2 adults, because a set of Hox genes is de-repressed in F2 embryos, resulting in homeotic phenotypes. 26674417 6 37 theme activities 972:981 arg1 range 945:949 a range 943:949 a range of reduced catalytic activities 943:981 Structural and enzymatic comparison between human OGT (hOGT) and DmOGT informed the rational design of DmOGT point mutants with a range of reduced catalytic activities. 26674417 5 38 theme negligible 728:737 arg1 catalysis 743:751 negligible OGT catalysis 728:751 negligible OGT catalysis 728:751 Here we use a genetic approach to demonstrate that post-pupal Drosophila development can proceed with negligible OGT catalysis, while early embryonic development is OGT activity-dependent. 26674417 0 39 theme transferase 31:41 arg1 functionality 5:17 Dual functionality 0:17 Dual functionality of O-GlcNAc transferase 0:41 Dual functionality of O-GlcNAc transferase is required for Drosophila development. 26674417 6 40 theme catalytic 962:970 arg1 activities 972:981 reduced catalytic activities 954:981 reduced catalytic activities 954:981 Structural and enzymatic comparison between human OGT (hOGT) and DmOGT informed the rational design of DmOGT point mutants with a range of reduced catalytic activities. 26674417 5 41 theme OGT 739:741 arg1 catalysis 743:751 negligible OGT catalysis 728:751 negligible OGT catalysis 728:751 Here we use a genetic approach to demonstrate that post-pupal Drosophila development can proceed with negligible OGT catalysis, while early embryonic development is OGT activity-dependent. 26674417 9 42 theme OGT 1239:1241 arg1 activity 1253:1260 OGT catalytic activity 1239:1260 OGT catalytic activity 1239:1260 Thus, OGT catalytic activity is required up to late pupal stages, while further development proceeds with severely reduced OGT activity. 26674417 0 43 theme O-GlcNAc 22:29 arg1 transferase 31:41 O-GlcNAc transferase 22:41 O-GlcNAc transferase 22:41 Dual functionality of O-GlcNAc transferase is required for Drosophila development. 26674417 7 44 theme sxc 1042:1044 arg1 lethality 1052:1060 sxc pupal lethality 1042:1060 sxc pupal lethality 1042:1060 Strikingly, a severely hypomorphic OGT mutant complements sxc pupal lethality. 26674417 6 45 theme reduced 954:960 arg1 activities 972:981 reduced catalytic activities 954:981 reduced catalytic activities 954:981 Structural and enzymatic comparison between human OGT (hOGT) and DmOGT informed the rational design of DmOGT point mutants with a range of reduced catalytic activities. 26674417 5 46 theme post-pupal 677:686 arg1 development 699:709 post-pupal Drosophila development 677:709 post-pupal Drosophila development 677:709 Here we use a genetic approach to demonstrate that post-pupal Drosophila development can proceed with negligible OGT catalysis, while early embryonic development is OGT activity-dependent. 26674417 3 47 theme sex 488:490 arg1 sxc 499:501 sxc 499:501 sxc 499:501 Drosophila OGT (DmOGT) is encoded by super sex combs (sxc), mutants of which are pupal lethal. 26674417 3 47 theme sex 488:490 arg1 combs 492:496 super sex combs 482:496 super sex combs (sxc) 482:502 Drosophila OGT (DmOGT) is encoded by super sex combs (sxc), mutants of which are pupal lethal. 26674417 7 48 theme pupal 1046:1050 arg1 lethality 1052:1060 sxc pupal lethality 1042:1060 sxc pupal lethality 1042:1060 Strikingly, a severely hypomorphic OGT mutant complements sxc pupal lethality. 26674417 5 49 theme Drosophila 688:697 arg1 development 699:709 post-pupal Drosophila development 677:709 post-pupal Drosophila development 677:709 Here we use a genetic approach to demonstrate that post-pupal Drosophila development can proceed with negligible OGT catalysis, while early embryonic development is OGT activity-dependent. 26674417 8 50 from embryos 1190:1196 arg1 de-repressed 1171:1182 de-repressed 1171:1182 de-repressed 1171:1182 However, the hypomorphic OGT mutant-rescued progeny do not produce F2 adults, because a set of Hox genes is de-repressed in F2 embryos, resulting in homeotic phenotypes. 26674417 8 50 from embryos 1190:1196 arg1 set 1151:1153 a set 1149:1153 a set of Hox genes 1149:1166 However, the hypomorphic OGT mutant-rescued progeny do not produce F2 adults, because a set of Hox genes is de-repressed in F2 embryos, resulting in homeotic phenotypes. 26674417 8 50 from embryos 1190:1196 arg1 genes 1162:1166 Hox genes 1158:1166 Hox genes 1158:1166 However, the hypomorphic OGT mutant-rescued progeny do not produce F2 adults, because a set of Hox genes is de-repressed in F2 embryos, resulting in homeotic phenotypes. 26674417 1 51 theme O-linked 146:153 arg1 N-acetylglucosamine 155:173 O-linked N-acetylglucosamine 146:173 O-linked N-acetylglucosamine (O-GlcNAc) catalysed by O-GlcNAc transferase (OGT) 146:224 Post-translational modification of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc) catalysed by O-GlcNAc transferase (OGT) has been linked to regulation of diverse cellular functions. 26674417 1 51 theme O-linked 146:153 arg1 O-GlcNAc 176:183 O-GlcNAc 176:183 O-GlcNAc 176:183 Post-translational modification of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc) catalysed by O-GlcNAc transferase (OGT) has been linked to regulation of diverse cellular functions. 26674417 8 52 from de-repressed 1171:1182 arg1 embryos 1190:1196 F2 embryos 1187:1196 F2 embryos 1187:1196 However, the hypomorphic OGT mutant-rescued progeny do not produce F2 adults, because a set of Hox genes is de-repressed in F2 embryos, resulting in homeotic phenotypes. 26674417 9 53 theme reduced 1348:1354 arg1 activity 1360:1367 severely reduced OGT activity 1339:1367 severely reduced OGT activity 1339:1367 Thus, OGT catalytic activity is required up to late pupal stages, while further development proceeds with severely reduced OGT activity. 26674417 4 54 theme O-GlcNAcylation 609:623 arg1 reduction 596:604 reduction 596:604 reduction of O-GlcNAcylation 596:623 However, it is not clear if this phenotype is caused by reduction of O-GlcNAcylation. 26674417 1 55 link O-linked 146:153 arg1 N-acetylglucosamine 155:173 O-linked N-acetylglucosamine 146:173 O-linked N-acetylglucosamine (O-GlcNAc) catalysed by O-GlcNAc transferase (OGT) 146:224 Post-translational modification of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc) catalysed by O-GlcNAc transferase (OGT) has been linked to regulation of diverse cellular functions. 26674417 1 55 link O-linked 146:153 arg1 O-GlcNAc 176:183 O-GlcNAc 176:183 O-GlcNAc 176:183 Post-translational modification of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc) catalysed by O-GlcNAc transferase (OGT) has been linked to regulation of diverse cellular functions. 26674417 1 56 attach linked 235:240 arg2 modification 102:113 Post-translational modification 83:113 Post-translational modification of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc) catalysed by O-GlcNAc transferase (OGT) 83:224 Post-translational modification of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc) catalysed by O-GlcNAc transferase (OGT) has been linked to regulation of diverse cellular functions. 26674417 1 56 attach linked 235:240 arg1 regulation 245:254 regulation 245:254 regulation of diverse cellular functions 245:284 Post-translational modification of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc) catalysed by O-GlcNAc transferase (OGT) has been linked to regulation of diverse cellular functions. 26674417 8 57 theme F2 1187:1188 arg1 embryos 1190:1196 F2 embryos 1187:1196 F2 embryos 1187:1196 However, the hypomorphic OGT mutant-rescued progeny do not produce F2 adults, because a set of Hox genes is de-repressed in F2 embryos, resulting in homeotic phenotypes. 26674417 7 58 theme hypomorphic 1007:1017 arg1 mutant 1023:1028 a severely hypomorphic OGT mutant 996:1028 a severely hypomorphic OGT mutant 996:1028 Strikingly, a severely hypomorphic OGT mutant complements sxc pupal lethality. 26674417 2 59 theme tetratricopeptide 366:382 arg1 repeats 384:390 N-terminal tetratricopeptide repeats 355:390 N-terminal tetratricopeptide repeats 355:390 OGT possesses a C-terminal glycosyltransferase catalytic domain and N-terminal tetratricopeptide repeats that are implicated in protein-protein interactions. 26674417 9 60 theme OGT 1356:1358 arg1 activity 1360:1367 severely reduced OGT activity 1339:1367 severely reduced OGT activity 1339:1367 Thus, OGT catalytic activity is required up to late pupal stages, while further development proceeds with severely reduced OGT activity. 26674417 5 61 theme embryonic 766:774 arg1 development 776:786 early embryonic development 760:786 early embryonic development 760:786 Here we use a genetic approach to demonstrate that post-pupal Drosophila development can proceed with negligible OGT catalysis, while early embryonic development is OGT activity-dependent. 26674417 7 62 theme OGT 1019:1021 arg1 mutant 1023:1028 a severely hypomorphic OGT mutant 996:1028 a severely hypomorphic OGT mutant 996:1028 Strikingly, a severely hypomorphic OGT mutant complements sxc pupal lethality. 26674417 0 63 theme Drosophila 59:68 arg1 development 70:80 Drosophila development 59:80 Drosophila development 59:80 Dual functionality of O-GlcNAc transferase is required for Drosophila development. 26674417 9 64 theme pupal 1285:1289 arg1 stages 1291:1296 late pupal stages 1280:1296 late pupal stages 1280:1296 Thus, OGT catalytic activity is required up to late pupal stages, while further development proceeds with severely reduced OGT activity. 26674417 2 65 theme protein-protein 415:429 arg1 interactions 431:442 protein-protein interactions 415:442 protein-protein interactions 415:442 OGT possesses a C-terminal glycosyltransferase catalytic domain and N-terminal tetratricopeptide repeats that are implicated in protein-protein interactions. 26674417 1 66 theme diverse 259:265 arg1 functions 276:284 diverse cellular functions 259:284 diverse cellular functions 259:284 Post-translational modification of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc) catalysed by O-GlcNAc transferase (OGT) has been linked to regulation of diverse cellular functions. 26031751 7 0 theme NPC 1200:1202 arg1 glycosylation 1179:1191 conserved glycosylation 1169:1191 conserved glycosylation of the NPC among metazoans 1169:1218 The results implicate NPC glycosylation as a regulator of NPC function and reveal the role of conserved glycosylation of the NPC among metazoans. 26031751 4 1 theme increased 672:680 arg1 degradation 694:704 their increased proteasomal degradation 666:704 their increased proteasomal degradation 666:704 Loss of O-GlcNAc enables increased ubiquitination of these Nups and their increased proteasomal degradation. 26031751 6 2 theme NPC 996:998 arg1 modification 976:987 O-GlcNAc modification 967:987 O-GlcNAc modification of the NPC 967:998 These findings define a critical role of O-GlcNAc modification of the NPC in maintaining its composition and the function of the selectivity filter. 26031751 5 3 theme post-mitotic 906:917 arg1 cells 919:923 both dividing and post-mitotic cells 888:923 both dividing and post-mitotic cells 888:923 The decreased half-life of these deglycosylated Nups manifests in their gradual loss from the NPC and a downstream malfunction of the nuclear pore selective permeability barrier in both dividing and post-mitotic cells. 26031751 5 4 theme dividing 893:900 arg1 cells 919:923 both dividing and post-mitotic cells 888:923 both dividing and post-mitotic cells 888:923 The decreased half-life of these deglycosylated Nups manifests in their gradual loss from the NPC and a downstream malfunction of the nuclear pore selective permeability barrier in both dividing and post-mitotic cells. 26031751 0 5 theme selectivity 103:113 arg1 filter 115:120 the pore selectivity filter 94:120 the pore selectivity filter 94:120 Post-translational O-GlcNAcylation is essential for nuclear pore integrity and maintenance of the pore selectivity filter. 26031751 0 6 theme pore 98:101 arg1 filter 115:120 the pore selectivity filter 94:120 the pore selectivity filter 94:120 Post-translational O-GlcNAcylation is essential for nuclear pore integrity and maintenance of the pore selectivity filter. 26031751 5 7 from barrier 877:883 arg1 cells 919:923 both dividing and post-mitotic cells 888:923 both dividing and post-mitotic cells 888:923 The decreased half-life of these deglycosylated Nups manifests in their gradual loss from the NPC and a downstream malfunction of the nuclear pore selective permeability barrier in both dividing and post-mitotic cells. 26031751 5 8 gly deglycosylated 740:753 arg1 Nups 755:758 these deglycosylated Nups 734:758 these deglycosylated Nups 734:758 The decreased half-life of these deglycosylated Nups manifests in their gradual loss from the NPC and a downstream malfunction of the nuclear pore selective permeability barrier in both dividing and post-mitotic cells. 26031751 6 9 theme modification 976:987 arg1 function 1039:1046 the function 1035:1046 the function of the selectivity filter 1035:1072 These findings define a critical role of O-GlcNAc modification of the NPC in maintaining its composition and the function of the selectivity filter. 26031751 6 9 theme modification 976:987 arg1 role 959:962 a critical role 948:962 a critical role of O-GlcNAc modification of the NPC in maintaining its composition 948:1029 These findings define a critical role of O-GlcNAc modification of the NPC in maintaining its composition and the function of the selectivity filter. 26031751 7 10 theme conserved 1169:1177 arg1 glycosylation 1179:1191 conserved glycosylation 1169:1191 conserved glycosylation of the NPC among metazoans 1169:1218 The results implicate NPC glycosylation as a regulator of NPC function and reveal the role of conserved glycosylation of the NPC among metazoans. 26031751 1 11 link O-linked 176:183 arg1 O-GlcNAc 206:213 O-GlcNAc 206:213 O-GlcNAc 206:213 O-glycosylation of the nuclear pore complex (NPC) by O-linked N-acetylglucosamine (O-GlcNAc) is conserved within metazoans. 26031751 1 11 link O-linked 176:183 arg1 N-acetylglucosamine 185:203 O-linked N-acetylglucosamine 176:203 O-linked N-acetylglucosamine (O-GlcNAc) 176:214 O-glycosylation of the nuclear pore complex (NPC) by O-linked N-acetylglucosamine (O-GlcNAc) is conserved within metazoans. 26031751 7 12 gly glycosylation 1179:1191 arg1 NPC 1200:1202 the NPC 1196:1202 the NPC 1196:1202 The results implicate NPC glycosylation as a regulator of NPC function and reveal the role of conserved glycosylation of the NPC among metazoans. 26031751 5 13 theme selective 854:862 arg1 barrier 877:883 selective permeability barrier 854:883 selective permeability barrier in both dividing and post-mitotic cells 854:923 The decreased half-life of these deglycosylated Nups manifests in their gradual loss from the NPC and a downstream malfunction of the nuclear pore selective permeability barrier in both dividing and post-mitotic cells. 26031751 5 14 theme nuclear 841:847 arg1 pore 849:852 the nuclear pore 837:852 the nuclear pore 837:852 The decreased half-life of these deglycosylated Nups manifests in their gradual loss from the NPC and a downstream malfunction of the nuclear pore selective permeability barrier in both dividing and post-mitotic cells. 26031751 0 15 theme filter 115:120 arg1 maintenance 79:89 maintenance 79:89 maintenance 79:89 Post-translational O-GlcNAcylation is essential for nuclear pore integrity and maintenance of the pore selectivity filter. 26031751 0 15 theme filter 115:120 arg1 integrity 65:73 nuclear pore integrity 52:73 nuclear pore integrity 52:73 Post-translational O-GlcNAcylation is essential for nuclear pore integrity and maintenance of the pore selectivity filter. 26031751 6 16 mod modification 976:987 arg3 O-GlcNAc 967:974 O-GlcNAc modification 967:987 O-GlcNAc modification of the NPC 967:998 These findings define a critical role of O-GlcNAc modification of the NPC in maintaining its composition and the function of the selectivity filter. 26031751 6 16 mod modification 976:987 arg1 NPC 996:998 the NPC 992:998 the NPC 992:998 These findings define a critical role of O-GlcNAc modification of the NPC in maintaining its composition and the function of the selectivity filter. 26031751 4 17 theme increased 623:631 arg1 ubiquitination 633:646 increased ubiquitination 623:646 increased ubiquitination of these Nups 623:660 Loss of O-GlcNAc enables increased ubiquitination of these Nups and their increased proteasomal degradation. 26031751 5 18 from NPC 801:803 arg1 loss 787:790 their gradual loss 773:790 their gradual loss from the NPC 773:803 The decreased half-life of these deglycosylated Nups manifests in their gradual loss from the NPC and a downstream malfunction of the nuclear pore selective permeability barrier in both dividing and post-mitotic cells. 26031751 5 18 from NPC 801:803 arg1 malfunction 822:832 a downstream malfunction 809:832 a downstream malfunction of the nuclear pore 809:852 The decreased half-life of these deglycosylated Nups manifests in their gradual loss from the NPC and a downstream malfunction of the nuclear pore selective permeability barrier in both dividing and post-mitotic cells. 26031751 3 19 theme cellular 537:544 arg1 levels 546:551 decreased cellular levels 527:551 decreased cellular levels of a number of natively O-GlcNAcylated Nups 527:595 We show that loss of O-GlcNAc, induced by either inhibition of O-GlcNAc transferase (OGT) or deletion of the gene encoding OGT, leads to decreased cellular levels of a number of natively O-GlcNAcylated Nups. 26031751 6 20 theme selectivity 1055:1065 arg1 filter 1067:1072 the selectivity filter 1051:1072 the selectivity filter 1051:1072 These findings define a critical role of O-GlcNAc modification of the NPC in maintaining its composition and the function of the selectivity filter. 26031751 1 21 theme O-linked 176:183 arg1 O-GlcNAc 206:213 O-GlcNAc 206:213 O-GlcNAc 206:213 O-glycosylation of the nuclear pore complex (NPC) by O-linked N-acetylglucosamine (O-GlcNAc) is conserved within metazoans. 26031751 1 21 theme O-linked 176:183 arg1 N-acetylglucosamine 185:203 O-linked N-acetylglucosamine 176:203 O-linked N-acetylglucosamine (O-GlcNAc) 176:214 O-glycosylation of the nuclear pore complex (NPC) by O-linked N-acetylglucosamine (O-GlcNAc) is conserved within metazoans. 26031751 0 22 theme Post-translational 0:17 arg1 O-GlcNAcylation 19:33 Post-translational O-GlcNAcylation 0:33 Post-translational O-GlcNAcylation 0:33 Post-translational O-GlcNAcylation is essential for nuclear pore integrity and maintenance of the pore selectivity filter. 26031751 6 23 theme O-GlcNAc 967:974 arg1 modification 976:987 O-GlcNAc modification 967:987 O-GlcNAc modification of the NPC 967:998 These findings define a critical role of O-GlcNAc modification of the NPC in maintaining its composition and the function of the selectivity filter. 26031751 7 24 theme function 1137:1144 arg1 glycosylation 1101:1113 NPC glycosylation 1097:1113 NPC glycosylation 1097:1113 The results implicate NPC glycosylation as a regulator of NPC function and reveal the role of conserved glycosylation of the NPC among metazoans. 26031751 7 24 theme function 1137:1144 arg1 regulator 1120:1128 a regulator 1118:1128 a regulator of NPC function 1118:1144 The results implicate NPC glycosylation as a regulator of NPC function and reveal the role of conserved glycosylation of the NPC among metazoans. 26031751 6 25 theme critical 950:957 arg1 role 959:962 a critical role 948:962 a critical role of O-GlcNAc modification of the NPC in maintaining its composition 948:1029 These findings define a critical role of O-GlcNAc modification of the NPC in maintaining its composition and the function of the selectivity filter. 26031751 0 26 theme pore 60:63 arg1 integrity 65:73 nuclear pore integrity 52:73 nuclear pore integrity 52:73 Post-translational O-GlcNAcylation is essential for nuclear pore integrity and maintenance of the pore selectivity filter. 26031751 5 27 theme permeability 864:875 arg1 barrier 877:883 selective permeability barrier 854:883 selective permeability barrier in both dividing and post-mitotic cells 854:923 The decreased half-life of these deglycosylated Nups manifests in their gradual loss from the NPC and a downstream malfunction of the nuclear pore selective permeability barrier in both dividing and post-mitotic cells. 26031751 6 28 theme filter 1067:1072 arg1 function 1039:1046 the function 1035:1046 the function of the selectivity filter 1035:1072 These findings define a critical role of O-GlcNAc modification of the NPC in maintaining its composition and the function of the selectivity filter. 26031751 6 28 theme filter 1067:1072 arg1 role 959:962 a critical role 948:962 a critical role of O-GlcNAc modification of the NPC in maintaining its composition 948:1029 These findings define a critical role of O-GlcNAc modification of the NPC in maintaining its composition and the function of the selectivity filter. 26031751 7 29 theme NPC 1097:1099 arg1 glycosylation 1101:1113 NPC glycosylation 1097:1113 NPC glycosylation 1097:1113 The results implicate NPC glycosylation as a regulator of NPC function and reveal the role of conserved glycosylation of the NPC among metazoans. 26031751 7 29 theme NPC 1097:1099 arg1 regulator 1120:1128 a regulator 1118:1128 a regulator of NPC function 1118:1144 The results implicate NPC glycosylation as a regulator of NPC function and reveal the role of conserved glycosylation of the NPC among metazoans. 26031751 3 30 theme O-GlcNAc 453:460 arg1 OGT 475:477 OGT 475:477 OGT 475:477 We show that loss of O-GlcNAc, induced by either inhibition of O-GlcNAc transferase (OGT) or deletion of the gene encoding OGT, leads to decreased cellular levels of a number of natively O-GlcNAcylated Nups. 26031751 3 30 theme O-GlcNAc 453:460 arg1 transferase 462:472 O-GlcNAc transferase 453:472 O-GlcNAc transferase (OGT) 453:478 We show that loss of O-GlcNAc, induced by either inhibition of O-GlcNAc transferase (OGT) or deletion of the gene encoding OGT, leads to decreased cellular levels of a number of natively O-GlcNAcylated Nups. 26031751 1 31 gly O-glycosylation 123:137 arg1 complex 159:165 nuclear pore complex 146:165 the nuclear pore complex (NPC) 142:171 O-glycosylation of the nuclear pore complex (NPC) by O-linked N-acetylglucosamine (O-GlcNAc) is conserved within metazoans. 26031751 1 31 gly O-glycosylation 123:137 arg1 NPC 168:170 NPC 168:170 NPC 168:170 O-glycosylation of the nuclear pore complex (NPC) by O-linked N-acetylglucosamine (O-GlcNAc) is conserved within metazoans. 26031751 3 32 theme decreased 527:535 arg1 levels 546:551 decreased cellular levels 527:551 decreased cellular levels of a number of natively O-GlcNAcylated Nups 527:595 We show that loss of O-GlcNAc, induced by either inhibition of O-GlcNAc transferase (OGT) or deletion of the gene encoding OGT, leads to decreased cellular levels of a number of natively O-GlcNAcylated Nups. 26031751 3 33 theme transferase 462:472 arg1 deletion 483:490 deletion 483:490 deletion of the gene encoding OGT 483:515 We show that loss of O-GlcNAc, induced by either inhibition of O-GlcNAc transferase (OGT) or deletion of the gene encoding OGT, leads to decreased cellular levels of a number of natively O-GlcNAcylated Nups. 26031751 3 33 theme transferase 462:472 arg1 inhibition 439:448 inhibition 439:448 inhibition of O-GlcNAc transferase (OGT) 439:478 We show that loss of O-GlcNAc, induced by either inhibition of O-GlcNAc transferase (OGT) or deletion of the gene encoding OGT, leads to decreased cellular levels of a number of natively O-GlcNAcylated Nups. 26031751 0 34 theme nuclear 52:58 arg1 integrity 65:73 nuclear pore integrity 52:73 nuclear pore integrity 52:73 Post-translational O-GlcNAcylation is essential for nuclear pore integrity and maintenance of the pore selectivity filter. 26031751 4 35 theme proteasomal 682:692 arg1 degradation 694:704 their increased proteasomal degradation 666:704 their increased proteasomal degradation 666:704 Loss of O-GlcNAc enables increased ubiquitination of these Nups and their increased proteasomal degradation. 26031751 3 36 theme number 558:563 arg1 levels 546:551 decreased cellular levels 527:551 decreased cellular levels of a number of natively O-GlcNAcylated Nups 527:595 We show that loss of O-GlcNAc, induced by either inhibition of O-GlcNAc transferase (OGT) or deletion of the gene encoding OGT, leads to decreased cellular levels of a number of natively O-GlcNAcylated Nups. 26031751 3 37 theme O-GlcNAc 411:418 arg1 loss 403:406 loss 403:406 loss 403:406 We show that loss of O-GlcNAc, induced by either inhibition of O-GlcNAc transferase (OGT) or deletion of the gene encoding OGT, leads to decreased cellular levels of a number of natively O-GlcNAcylated Nups. 26031751 5 38 theme gradual 779:785 arg1 loss 787:790 their gradual loss 773:790 their gradual loss from the NPC 773:803 The decreased half-life of these deglycosylated Nups manifests in their gradual loss from the NPC and a downstream malfunction of the nuclear pore selective permeability barrier in both dividing and post-mitotic cells. 26031751 4 39 theme O-GlcNAc 606:613 arg1 Loss 598:601 Loss 598:601 Loss of O-GlcNAc 598:613 Loss of O-GlcNAc enables increased ubiquitination of these Nups and their increased proteasomal degradation. 26031751 5 40 theme decreased 711:719 arg1 half-life 721:729 The decreased half-life 707:729 The decreased half-life of these deglycosylated Nups 707:758 The decreased half-life of these deglycosylated Nups manifests in their gradual loss from the NPC and a downstream malfunction of the nuclear pore selective permeability barrier in both dividing and post-mitotic cells. 26031751 2 41 theme modification 358:369 arg1 role 345:348 the functional role 330:348 the functional role of this modification 330:369 Many nucleoporins (Nups) comprising the NPC are constitutively O-GlcNAcylated, but the functional role of this modification remains enigmatic. 26031751 7 42 theme glycosylation 1179:1191 arg1 role 1161:1164 the role 1157:1164 the role of conserved glycosylation of the NPC among metazoans 1157:1218 The results implicate NPC glycosylation as a regulator of NPC function and reveal the role of conserved glycosylation of the NPC among metazoans. 26031751 1 43 theme complex 159:165 arg1 O-glycosylation 123:137 O-glycosylation 123:137 O-glycosylation of the nuclear pore complex (NPC) by O-linked N-acetylglucosamine (O-GlcNAc) 123:214 O-glycosylation of the nuclear pore complex (NPC) by O-linked N-acetylglucosamine (O-GlcNAc) is conserved within metazoans. 26031751 2 44 theme functional 334:343 arg1 role 345:348 the functional role 330:348 the functional role of this modification 330:369 Many nucleoporins (Nups) comprising the NPC are constitutively O-GlcNAcylated, but the functional role of this modification remains enigmatic. 26031751 3 45 theme O-GlcNAcylated 577:590 arg1 Nups 592:595 natively O-GlcNAcylated Nups 568:595 natively O-GlcNAcylated Nups 568:595 We show that loss of O-GlcNAc, induced by either inhibition of O-GlcNAc transferase (OGT) or deletion of the gene encoding OGT, leads to decreased cellular levels of a number of natively O-GlcNAcylated Nups. 26031751 7 46 theme NPC 1133:1135 arg1 function 1137:1144 NPC function 1133:1144 NPC function 1133:1144 The results implicate NPC glycosylation as a regulator of NPC function and reveal the role of conserved glycosylation of the NPC among metazoans. 26031751 3 47 theme Nups 592:595 arg1 number 558:563 a number 556:563 a number of natively O-GlcNAcylated Nups 556:595 We show that loss of O-GlcNAc, induced by either inhibition of O-GlcNAc transferase (OGT) or deletion of the gene encoding OGT, leads to decreased cellular levels of a number of natively O-GlcNAcylated Nups. 26031751 4 48 theme Nups 657:660 arg1 ubiquitination 633:646 increased ubiquitination 623:646 increased ubiquitination of these Nups 623:660 Loss of O-GlcNAc enables increased ubiquitination of these Nups and their increased proteasomal degradation. 26031751 4 48 theme Nups 657:660 arg1 degradation 694:704 their increased proteasomal degradation 666:704 their increased proteasomal degradation 666:704 Loss of O-GlcNAc enables increased ubiquitination of these Nups and their increased proteasomal degradation. 26031751 1 49 theme nuclear 146:152 arg1 complex 159:165 nuclear pore complex 146:165 the nuclear pore complex (NPC) 142:171 O-glycosylation of the nuclear pore complex (NPC) by O-linked N-acetylglucosamine (O-GlcNAc) is conserved within metazoans. 26031751 1 49 theme nuclear 146:152 arg1 NPC 168:170 NPC 168:170 NPC 168:170 O-glycosylation of the nuclear pore complex (NPC) by O-linked N-acetylglucosamine (O-GlcNAc) is conserved within metazoans. 26031751 5 50 theme deglycosylated 740:753 arg1 Nups 755:758 these deglycosylated Nups 734:758 these deglycosylated Nups 734:758 The decreased half-life of these deglycosylated Nups manifests in their gradual loss from the NPC and a downstream malfunction of the nuclear pore selective permeability barrier in both dividing and post-mitotic cells. 26031751 5 51 theme downstream 811:820 arg1 malfunction 822:832 a downstream malfunction 809:832 a downstream malfunction of the nuclear pore 809:852 The decreased half-life of these deglycosylated Nups manifests in their gradual loss from the NPC and a downstream malfunction of the nuclear pore selective permeability barrier in both dividing and post-mitotic cells. 26031751 1 52 theme pore 154:157 arg1 complex 159:165 nuclear pore complex 146:165 the nuclear pore complex (NPC) 142:171 O-glycosylation of the nuclear pore complex (NPC) by O-linked N-acetylglucosamine (O-GlcNAc) is conserved within metazoans. 26031751 1 52 theme pore 154:157 arg1 NPC 168:170 NPC 168:170 NPC 168:170 O-glycosylation of the nuclear pore complex (NPC) by O-linked N-acetylglucosamine (O-GlcNAc) is conserved within metazoans. 26031751 5 53 theme pore 849:852 arg1 loss 787:790 their gradual loss 773:790 their gradual loss from the NPC 773:803 The decreased half-life of these deglycosylated Nups manifests in their gradual loss from the NPC and a downstream malfunction of the nuclear pore selective permeability barrier in both dividing and post-mitotic cells. 26031751 5 53 theme pore 849:852 arg1 malfunction 822:832 a downstream malfunction 809:832 a downstream malfunction of the nuclear pore 809:852 The decreased half-life of these deglycosylated Nups manifests in their gradual loss from the NPC and a downstream malfunction of the nuclear pore selective permeability barrier in both dividing and post-mitotic cells. 26031751 5 54 theme Nups 755:758 arg1 half-life 721:729 The decreased half-life 707:729 The decreased half-life of these deglycosylated Nups 707:758 The decreased half-life of these deglycosylated Nups manifests in their gradual loss from the NPC and a downstream malfunction of the nuclear pore selective permeability barrier in both dividing and post-mitotic cells. 26031751 2 55 theme Many 247:250 arg1 nucleoporins 252:263 Many nucleoporins 247:263 Many nucleoporins (Nups) comprising the NPC 247:289 Many nucleoporins (Nups) comprising the NPC are constitutively O-GlcNAcylated, but the functional role of this modification remains enigmatic. 26031751 2 55 theme Many 247:250 arg1 Nups 266:269 Nups 266:269 Nups 266:269 Many nucleoporins (Nups) comprising the NPC are constitutively O-GlcNAcylated, but the functional role of this modification remains enigmatic. 26031751 3 56 theme gene 499:502 arg1 deletion 483:490 deletion 483:490 deletion of the gene encoding OGT 483:515 We show that loss of O-GlcNAc, induced by either inhibition of O-GlcNAc transferase (OGT) or deletion of the gene encoding OGT, leads to decreased cellular levels of a number of natively O-GlcNAcylated Nups. 26031751 3 56 theme gene 499:502 arg1 inhibition 439:448 inhibition 439:448 inhibition of O-GlcNAc transferase (OGT) 439:478 We show that loss of O-GlcNAc, induced by either inhibition of O-GlcNAc transferase (OGT) or deletion of the gene encoding OGT, leads to decreased cellular levels of a number of natively O-GlcNAcylated Nups. 25856312 9 0 theme assumed 1582:1588 arg1 property 1614:1621 its assumed essential physiological property 1578:1621 its assumed essential physiological property 1578:1621 Together our results suggest that the cis-inhibitory activity of DLL3 observed in cultured cells might not fully reflect its assumed essential physiological property, suggest that DLL3 and LFNG act together, and strongly supports that modification of DLL3 by O-linked fucose is essential for its function during somitogenesis. 25856312 1 1 from ligands 133:139 arg1 amniotes 144:151 amniotes 144:151 amniotes 144:151 Delta-like 3 (DLL3) is a member of the DSL family of Notch ligands in amniotes. 25856312 1 2 theme family 117:122 arg1 member 99:104 a member 97:104 a member of the DSL family of Notch ligands in amniotes 97:151 Delta-like 3 (DLL3) is a member of the DSL family of Notch ligands in amniotes. 25856312 1 2 theme family 117:122 arg1 3 85:85 3 85:85 3 85:85 Delta-like 3 (DLL3) is a member of the DSL family of Notch ligands in amniotes. 25856312 9 3 theme DLL3 1708:1711 arg1 modification 1692:1703 modification 1692:1703 modification of DLL3 by O-linked fucose 1692:1730 Together our results suggest that the cis-inhibitory activity of DLL3 observed in cultured cells might not fully reflect its assumed essential physiological property, suggest that DLL3 and LFNG act together, and strongly supports that modification of DLL3 by O-linked fucose is essential for its function during somitogenesis. 25856312 7 4 theme O-fucosylation-deficient 1230:1253 arg1 DLL3 1255:1258 O-fucosylation-deficient DLL3 1230:1258 O-fucosylation-deficient DLL3 1230:1258 Mutation of the O-fucosylation sites in DLL3 does not disrupt the interaction of DLL3 with LFNG or full length Notch1or DLL1, and O-fucosylation-deficient DLL3 can still inhibit Notch in cis in vitro. 25856312 8 5 theme wild 1325:1328 arg1 DLL3 1335:1338 wild type DLL3 1325:1338 wild type DLL3 1325:1338 However, in contrast to wild type DLL3, O-fucosylation-deficient DLL3 cannot compensate for the loss of endogenous DLL3 during somitogenesis in the embryo. 25856312 1 6 from family 117:122 arg1 amniotes 144:151 amniotes 144:151 amniotes 144:151 Delta-like 3 (DLL3) is a member of the DSL family of Notch ligands in amniotes. 25856312 9 7 theme physiological 1600:1612 arg1 property 1614:1621 its assumed essential physiological property 1578:1621 its assumed essential physiological property 1578:1621 Together our results suggest that the cis-inhibitory activity of DLL3 observed in cultured cells might not fully reflect its assumed essential physiological property, suggest that DLL3 and LFNG act together, and strongly supports that modification of DLL3 by O-linked fucose is essential for its function during somitogenesis. 25856312 5 8 theme DLL3 831:834 arg1 factor 800:805 epidermal growth factor 783:805 epidermal growth factor like repeats 2 and 5 of DLL3 783:834 Here, we show that i) both proteins interact, ii) epidermal growth factor like repeats 2 and 5 of DLL3 are O-fucosylated at consensus sites for POFUT1, and iii) further modified by FNG proteins in vitro. 25856312 5 8 theme DLL3 831:834 arg1 sites 867:871 O-fucosylated at consensus sites 840:871 O-fucosylated at consensus sites for POFUT1 840:882 Here, we show that i) both proteins interact, ii) epidermal growth factor like repeats 2 and 5 of DLL3 are O-fucosylated at consensus sites for POFUT1, and iii) further modified by FNG proteins in vitro. 25856312 5 9 theme at 854:855 arg1 factor 800:805 epidermal growth factor 783:805 epidermal growth factor like repeats 2 and 5 of DLL3 783:834 Here, we show that i) both proteins interact, ii) epidermal growth factor like repeats 2 and 5 of DLL3 are O-fucosylated at consensus sites for POFUT1, and iii) further modified by FNG proteins in vitro. 25856312 5 9 theme at 854:855 arg1 sites 867:871 O-fucosylated at consensus sites 840:871 O-fucosylated at consensus sites for POFUT1 840:882 Here, we show that i) both proteins interact, ii) epidermal growth factor like repeats 2 and 5 of DLL3 are O-fucosylated at consensus sites for POFUT1, and iii) further modified by FNG proteins in vitro. 25856312 3 10 theme severe 439:444 arg1 defects 464:470 severe somite patterning defects 439:470 severe somite patterning defects 439:470 Loss of the DSL protein DLL3 in the mouse results in severe somite patterning defects, which are virtually indistinguishable from the defects in mice that lack lunatic fringe (LFNG), a glycosyltransferase involved in modifying Notch signaling. 25856312 9 11 theme O-linked 1716:1723 arg1 fucose 1725:1730 O-linked fucose 1716:1730 O-linked fucose 1716:1730 Together our results suggest that the cis-inhibitory activity of DLL3 observed in cultured cells might not fully reflect its assumed essential physiological property, suggest that DLL3 and LFNG act together, and strongly supports that modification of DLL3 by O-linked fucose is essential for its function during somitogenesis. 25856312 3 12 theme somite 446:451 arg1 defects 464:470 severe somite patterning defects 439:470 severe somite patterning defects 439:470 Loss of the DSL protein DLL3 in the mouse results in severe somite patterning defects, which are virtually indistinguishable from the defects in mice that lack lunatic fringe (LFNG), a glycosyltransferase involved in modifying Notch signaling. 25856312 3 13 theme DLL3 410:413 arg1 Loss 386:389 Loss 386:389 Loss of the DSL protein DLL3 in the mouse 386:426 Loss of the DSL protein DLL3 in the mouse results in severe somite patterning defects, which are virtually indistinguishable from the defects in mice that lack lunatic fringe (LFNG), a glycosyltransferase involved in modifying Notch signaling. 25856312 9 14 theme essential 1590:1598 arg1 property 1614:1621 its assumed essential physiological property 1578:1621 its assumed essential physiological property 1578:1621 Together our results suggest that the cis-inhibitory activity of DLL3 observed in cultured cells might not fully reflect its assumed essential physiological property, suggest that DLL3 and LFNG act together, and strongly supports that modification of DLL3 by O-linked fucose is essential for its function during somitogenesis. 25856312 9 15 located observed 1527:1534 arg2 activity 1510:1517 the cis-inhibitory activity 1491:1517 the cis-inhibitory activity of DLL3 observed in cultured cells 1491:1552 Together our results suggest that the cis-inhibitory activity of DLL3 observed in cultured cells might not fully reflect its assumed essential physiological property, suggest that DLL3 and LFNG act together, and strongly supports that modification of DLL3 by O-linked fucose is essential for its function during somitogenesis. 25856312 9 15 located observed 1527:1534 arg1 cells 1548:1552 cultured cells 1539:1552 cultured cells 1539:1552 Together our results suggest that the cis-inhibitory activity of DLL3 observed in cultured cells might not fully reflect its assumed essential physiological property, suggest that DLL3 and LFNG act together, and strongly supports that modification of DLL3 by O-linked fucose is essential for its function during somitogenesis. 25856312 6 16 theme homozygous 952:961 arg1 Embryos 937:943 Embryos 937:943 Embryos double homozygous for null mutations in Dll3 and Lfng 937:997 Embryos double homozygous for null mutations in Dll3 and Lfng are phenotypically indistinguishable from the single mutants supporting a potential common function. 25856312 7 17 theme Notch1or 1211:1218 arg1 DLL1 1220:1223 full length Notch1or DLL1 1199:1223 full length Notch1or DLL1 1199:1223 Mutation of the O-fucosylation sites in DLL3 does not disrupt the interaction of DLL3 with LFNG or full length Notch1or DLL1, and O-fucosylation-deficient DLL3 can still inhibit Notch in cis in vitro. 25856312 5 18 dep interact 769:776 arg1 i 752:752 i 752:752 i 752:752 Here, we show that i) both proteins interact, ii) epidermal growth factor like repeats 2 and 5 of DLL3 are O-fucosylated at consensus sites for POFUT1, and iii) further modified by FNG proteins in vitro. 25856312 3 19 from defects 520:526 arg1 indistinguishable 493:509 indistinguishable 493:509 indistinguishable 493:509 Loss of the DSL protein DLL3 in the mouse results in severe somite patterning defects, which are virtually indistinguishable from the defects in mice that lack lunatic fringe (LFNG), a glycosyltransferase involved in modifying Notch signaling. 25856312 3 19 from defects 520:526 arg1 mice 531:534 mice 531:534 mice that lack lunatic fringe (LFNG), a glycosyltransferase involved in modifying Notch signaling 531:627 Loss of the DSL protein DLL3 in the mouse results in severe somite patterning defects, which are virtually indistinguishable from the defects in mice that lack lunatic fringe (LFNG), a glycosyltransferase involved in modifying Notch signaling. 25856312 1 20 theme Notch 127:131 arg1 ligands 133:139 Notch ligands 127:139 Notch ligands in amniotes 127:151 Delta-like 3 (DLL3) is a member of the DSL family of Notch ligands in amniotes. 25856312 8 21 theme O-fucosylation-deficient 1341:1364 arg1 DLL3 1366:1369 O-fucosylation-deficient DLL3 1341:1369 O-fucosylation-deficient DLL3 1341:1369 However, in contrast to wild type DLL3, O-fucosylation-deficient DLL3 cannot compensate for the loss of endogenous DLL3 during somitogenesis in the embryo. 25856312 9 22 theme cis-inhibitory 1495:1508 arg1 activity 1510:1517 the cis-inhibitory activity 1491:1517 the cis-inhibitory activity of DLL3 observed in cultured cells 1491:1552 Together our results suggest that the cis-inhibitory activity of DLL3 observed in cultured cells might not fully reflect its assumed essential physiological property, suggest that DLL3 and LFNG act together, and strongly supports that modification of DLL3 by O-linked fucose is essential for its function during somitogenesis. 25856312 7 23 from Mutation 1100:1107 arg1 DLL3 1140:1143 DLL3 1140:1143 DLL3 1140:1143 Mutation of the O-fucosylation sites in DLL3 does not disrupt the interaction of DLL3 with LFNG or full length Notch1or DLL1, and O-fucosylation-deficient DLL3 can still inhibit Notch in cis in vitro. 25856312 1 24 theme ligands 133:139 arg1 family 117:122 the DSL family 109:122 the DSL family of Notch ligands in amniotes 109:151 Delta-like 3 (DLL3) is a member of the DSL family of Notch ligands in amniotes. 25856312 3 25 theme Notch 613:617 arg1 signaling 619:627 Notch signaling 613:627 Notch signaling 613:627 Loss of the DSL protein DLL3 in the mouse results in severe somite patterning defects, which are virtually indistinguishable from the defects in mice that lack lunatic fringe (LFNG), a glycosyltransferase involved in modifying Notch signaling. 25856312 6 26 theme common 1083:1088 arg1 function 1090:1097 a potential common function 1071:1097 a potential common function 1071:1097 Embryos double homozygous for null mutations in Dll3 and Lfng are phenotypically indistinguishable from the single mutants supporting a potential common function. 25856312 5 27 theme epidermal 783:791 arg1 factor 800:805 epidermal growth factor 783:805 epidermal growth factor like repeats 2 and 5 of DLL3 783:834 Here, we show that i) both proteins interact, ii) epidermal growth factor like repeats 2 and 5 of DLL3 are O-fucosylated at consensus sites for POFUT1, and iii) further modified by FNG proteins in vitro. 25856312 5 27 theme epidermal 783:791 arg1 sites 867:871 O-fucosylated at consensus sites 840:871 O-fucosylated at consensus sites for POFUT1 840:882 Here, we show that i) both proteins interact, ii) epidermal growth factor like repeats 2 and 5 of DLL3 are O-fucosylated at consensus sites for POFUT1, and iii) further modified by FNG proteins in vitro. 25856312 8 28 theme type 1330:1333 arg1 DLL3 1335:1338 wild type DLL3 1325:1338 wild type DLL3 1325:1338 However, in contrast to wild type DLL3, O-fucosylation-deficient DLL3 cannot compensate for the loss of endogenous DLL3 during somitogenesis in the embryo. 25856312 2 29 theme Notch 360:364 arg1 signaling 366:374 Notch signaling 360:374 Notch signaling 360:374 In contrast to DLL1 and DLL4, the other Delta-like proteins in the mouse, DLL3 does not bind in trans to Notch and does not activate the receptor, but shows cis-interaction and cis-inhibitory properties on Notch signaling in vitro. 25856312 6 30 theme potential 1073:1081 arg1 function 1090:1097 a potential common function 1071:1097 a potential common function 1071:1097 Embryos double homozygous for null mutations in Dll3 and Lfng are phenotypically indistinguishable from the single mutants supporting a potential common function. 25856312 5 31 theme growth 793:798 arg1 factor 800:805 epidermal growth factor 783:805 epidermal growth factor like repeats 2 and 5 of DLL3 783:834 Here, we show that i) both proteins interact, ii) epidermal growth factor like repeats 2 and 5 of DLL3 are O-fucosylated at consensus sites for POFUT1, and iii) further modified by FNG proteins in vitro. 25856312 5 31 theme growth 793:798 arg1 sites 867:871 O-fucosylated at consensus sites 840:871 O-fucosylated at consensus sites for POFUT1 840:882 Here, we show that i) both proteins interact, ii) epidermal growth factor like repeats 2 and 5 of DLL3 are O-fucosylated at consensus sites for POFUT1, and iii) further modified by FNG proteins in vitro. 25856312 5 32 from sites 867:871 arg1 consensus 857:865 O-fucosylated at consensus sites 840:871 O-fucosylated at consensus sites for POFUT1 840:882 Here, we show that i) both proteins interact, ii) epidermal growth factor like repeats 2 and 5 of DLL3 are O-fucosylated at consensus sites for POFUT1, and iii) further modified by FNG proteins in vitro. 25856312 5 32 from sites 867:871 arg1 at 854:855 O-fucosylated at consensus sites 840:871 O-fucosylated at consensus sites for POFUT1 840:882 Here, we show that i) both proteins interact, ii) epidermal growth factor like repeats 2 and 5 of DLL3 are O-fucosylated at consensus sites for POFUT1, and iii) further modified by FNG proteins in vitro. 25856312 4 33 located located 649:655 arg1 trans-Golgi 668:678 the trans-Golgi 664:678 the trans-Golgi 664:678 Like LFNG, DLL3 is located within the trans-Golgi, however, its biochemical function is still unclear. 25856312 4 33 located located 649:655 arg2 DLL3 641:644 DLL3 641:644 DLL3 641:644 Like LFNG, DLL3 is located within the trans-Golgi, however, its biochemical function is still unclear. 25856312 9 34 theme DLL3 1522:1525 arg1 activity 1510:1517 the cis-inhibitory activity 1491:1517 the cis-inhibitory activity of DLL3 observed in cultured cells 1491:1552 Together our results suggest that the cis-inhibitory activity of DLL3 observed in cultured cells might not fully reflect its assumed essential physiological property, suggest that DLL3 and LFNG act together, and strongly supports that modification of DLL3 by O-linked fucose is essential for its function during somitogenesis. 25856312 7 35 theme full 1199:1202 arg1 DLL1 1220:1223 full length Notch1or DLL1 1199:1223 full length Notch1or DLL1 1199:1223 Mutation of the O-fucosylation sites in DLL3 does not disrupt the interaction of DLL3 with LFNG or full length Notch1or DLL1, and O-fucosylation-deficient DLL3 can still inhibit Notch in cis in vitro. 25856312 3 36 theme patterning 453:462 arg1 defects 464:470 severe somite patterning defects 439:470 severe somite patterning defects 439:470 Loss of the DSL protein DLL3 in the mouse results in severe somite patterning defects, which are virtually indistinguishable from the defects in mice that lack lunatic fringe (LFNG), a glycosyltransferase involved in modifying Notch signaling. 25856312 4 37 theme biochemical 694:704 arg1 function 706:713 its biochemical function 690:713 its biochemical function 690:713 Like LFNG, DLL3 is located within the trans-Golgi, however, its biochemical function is still unclear. 25856312 2 38 theme cis-inhibitory 331:344 arg1 properties 346:355 cis-inhibitory properties 331:355 cis-inhibitory properties 331:355 In contrast to DLL1 and DLL4, the other Delta-like proteins in the mouse, DLL3 does not bind in trans to Notch and does not activate the receptor, but shows cis-interaction and cis-inhibitory properties on Notch signaling in vitro. 25856312 0 39 theme DLL3 18:21 arg1 O-fucosylation 0:13 O-fucosylation 0:13 O-fucosylation of DLL3 0:21 O-fucosylation of DLL3 is required for its function during somitogenesis. 25856312 8 40 from somitogenesis 1428:1440 arg1 embryo 1449:1454 the embryo 1445:1454 the embryo 1445:1454 However, in contrast to wild type DLL3, O-fucosylation-deficient DLL3 cannot compensate for the loss of endogenous DLL3 during somitogenesis in the embryo. 25856312 3 41 theme lunatic 546:552 arg1 LFNG 562:565 LFNG 562:565 LFNG 562:565 Loss of the DSL protein DLL3 in the mouse results in severe somite patterning defects, which are virtually indistinguishable from the defects in mice that lack lunatic fringe (LFNG), a glycosyltransferase involved in modifying Notch signaling. 25856312 3 41 theme lunatic 546:552 arg1 fringe 554:559 lunatic fringe 546:559 lunatic fringe (LFNG) 546:566 Loss of the DSL protein DLL3 in the mouse results in severe somite patterning defects, which are virtually indistinguishable from the defects in mice that lack lunatic fringe (LFNG), a glycosyltransferase involved in modifying Notch signaling. 25856312 3 41 theme lunatic 546:552 arg1 glycosyltransferase 571:589 a glycosyltransferase 569:589 a glycosyltransferase involved in modifying Notch signaling 569:627 Loss of the DSL protein DLL3 in the mouse results in severe somite patterning defects, which are virtually indistinguishable from the defects in mice that lack lunatic fringe (LFNG), a glycosyltransferase involved in modifying Notch signaling. 25856312 2 42 from proteins 205:212 arg1 mouse 221:225 the mouse 217:225 the mouse 217:225 In contrast to DLL1 and DLL4, the other Delta-like proteins in the mouse, DLL3 does not bind in trans to Notch and does not activate the receptor, but shows cis-interaction and cis-inhibitory properties on Notch signaling in vitro. 25856312 2 43 dep DLL1 169:172 arg1 contrast 157:164 contrast 157:164 contrast 157:164 In contrast to DLL1 and DLL4, the other Delta-like proteins in the mouse, DLL3 does not bind in trans to Notch and does not activate the receptor, but shows cis-interaction and cis-inhibitory properties on Notch signaling in vitro. 25856312 7 44 theme O-fucosylation 1116:1129 arg1 sites 1131:1135 the O-fucosylation sites 1112:1135 the O-fucosylation sites 1112:1135 Mutation of the O-fucosylation sites in DLL3 does not disrupt the interaction of DLL3 with LFNG or full length Notch1or DLL1, and O-fucosylation-deficient DLL3 can still inhibit Notch in cis in vitro. 25856312 9 45 link O-linked 1716:1723 arg1 fucose 1725:1730 O-linked fucose 1716:1730 O-linked fucose 1716:1730 Together our results suggest that the cis-inhibitory activity of DLL3 observed in cultured cells might not fully reflect its assumed essential physiological property, suggest that DLL3 and LFNG act together, and strongly supports that modification of DLL3 by O-linked fucose is essential for its function during somitogenesis. 25856312 0 46 gly O-fucosylation 0:13 arg1 DLL3 18:21 DLL3 18:21 DLL3 18:21 O-fucosylation of DLL3 is required for its function during somitogenesis. 25856312 6 47 from mutations 972:980 arg1 Lfng 994:997 Lfng 994:997 Lfng 994:997 Embryos double homozygous for null mutations in Dll3 and Lfng are phenotypically indistinguishable from the single mutants supporting a potential common function. 25856312 6 47 from mutations 972:980 arg1 Dll3 985:988 Dll3 985:988 Dll3 985:988 Embryos double homozygous for null mutations in Dll3 and Lfng are phenotypically indistinguishable from the single mutants supporting a potential common function. 25856312 7 48 theme sites 1131:1135 arg1 Mutation 1100:1107 Mutation 1100:1107 Mutation of the O-fucosylation sites in DLL3 1100:1143 Mutation of the O-fucosylation sites in DLL3 does not disrupt the interaction of DLL3 with LFNG or full length Notch1or DLL1, and O-fucosylation-deficient DLL3 can still inhibit Notch in cis in vitro. 25856312 5 49 dep sites 867:871 arg1 ii 779:780 ii 779:780 ii 779:780 Here, we show that i) both proteins interact, ii) epidermal growth factor like repeats 2 and 5 of DLL3 are O-fucosylated at consensus sites for POFUT1, and iii) further modified by FNG proteins in vitro. 25856312 9 50 theme cultured 1539:1546 arg1 cells 1548:1552 cultured cells 1539:1552 cultured cells 1539:1552 Together our results suggest that the cis-inhibitory activity of DLL3 observed in cultured cells might not fully reflect its assumed essential physiological property, suggest that DLL3 and LFNG act together, and strongly supports that modification of DLL3 by O-linked fucose is essential for its function during somitogenesis. 25856312 5 51 theme consensus 857:865 arg1 factor 800:805 epidermal growth factor 783:805 epidermal growth factor like repeats 2 and 5 of DLL3 783:834 Here, we show that i) both proteins interact, ii) epidermal growth factor like repeats 2 and 5 of DLL3 are O-fucosylated at consensus sites for POFUT1, and iii) further modified by FNG proteins in vitro. 25856312 5 51 theme consensus 857:865 arg1 sites 867:871 O-fucosylated at consensus sites 840:871 O-fucosylated at consensus sites for POFUT1 840:882 Here, we show that i) both proteins interact, ii) epidermal growth factor like repeats 2 and 5 of DLL3 are O-fucosylated at consensus sites for POFUT1, and iii) further modified by FNG proteins in vitro. 25856312 5 52 gly O-fucosylated 840:852 arg1 factor 800:805 epidermal growth factor 783:805 epidermal growth factor like repeats 2 and 5 of DLL3 783:834 Here, we show that i) both proteins interact, ii) epidermal growth factor like repeats 2 and 5 of DLL3 are O-fucosylated at consensus sites for POFUT1, and iii) further modified by FNG proteins in vitro. 25856312 5 52 gly O-fucosylated 840:852 arg1 sites 867:871 O-fucosylated at consensus sites 840:871 O-fucosylated at consensus sites for POFUT1 840:882 Here, we show that i) both proteins interact, ii) epidermal growth factor like repeats 2 and 5 of DLL3 are O-fucosylated at consensus sites for POFUT1, and iii) further modified by FNG proteins in vitro. 25856312 7 53 gly O-fucosylation 1116:1129 arg2 sites 1131:1135 the O-fucosylation sites 1112:1135 the O-fucosylation sites 1112:1135 Mutation of the O-fucosylation sites in DLL3 does not disrupt the interaction of DLL3 with LFNG or full length Notch1or DLL1, and O-fucosylation-deficient DLL3 can still inhibit Notch in cis in vitro. 25856312 3 54 theme DSL 398:400 arg1 DLL3 410:413 the DSL protein DLL3 394:413 the DSL protein DLL3 394:413 Loss of the DSL protein DLL3 in the mouse results in severe somite patterning defects, which are virtually indistinguishable from the defects in mice that lack lunatic fringe (LFNG), a glycosyltransferase involved in modifying Notch signaling. 25856312 8 55 theme endogenous 1405:1414 arg1 DLL3 1416:1419 endogenous DLL3 1405:1419 endogenous DLL3 1405:1419 However, in contrast to wild type DLL3, O-fucosylation-deficient DLL3 cannot compensate for the loss of endogenous DLL3 during somitogenesis in the embryo. 25856312 6 56 theme single 1045:1050 arg1 mutants 1052:1058 the single mutants 1041:1058 the single mutants supporting a potential common function 1041:1097 Embryos double homozygous for null mutations in Dll3 and Lfng are phenotypically indistinguishable from the single mutants supporting a potential common function. 25856312 3 57 theme protein 402:408 arg1 DLL3 410:413 the DSL protein DLL3 394:413 the DSL protein DLL3 394:413 Loss of the DSL protein DLL3 in the mouse results in severe somite patterning defects, which are virtually indistinguishable from the defects in mice that lack lunatic fringe (LFNG), a glycosyltransferase involved in modifying Notch signaling. 25856312 6 58 from mutants 1052:1058 arg1 indistinguishable 1018:1034 indistinguishable 1018:1034 indistinguishable 1018:1034 Embryos double homozygous for null mutations in Dll3 and Lfng are phenotypically indistinguishable from the single mutants supporting a potential common function. 25856312 7 59 theme DLL3 1181:1184 arg1 interaction 1166:1176 the interaction 1162:1176 the interaction of DLL3 with LFNG or full length Notch1or DLL1 1162:1223 Mutation of the O-fucosylation sites in DLL3 does not disrupt the interaction of DLL3 with LFNG or full length Notch1or DLL1, and O-fucosylation-deficient DLL3 can still inhibit Notch in cis in vitro. 25856312 3 60 from Loss 386:389 arg1 mouse 422:426 the mouse 418:426 the mouse 418:426 Loss of the DSL protein DLL3 in the mouse results in severe somite patterning defects, which are virtually indistinguishable from the defects in mice that lack lunatic fringe (LFNG), a glycosyltransferase involved in modifying Notch signaling. 25856312 6 61 theme null 967:970 arg1 mutations 972:980 null mutations 967:980 null mutations in Dll3 and Lfng 967:997 Embryos double homozygous for null mutations in Dll3 and Lfng are phenotypically indistinguishable from the single mutants supporting a potential common function. 25856312 5 62 dep modified 902:909 arg1 iii 889:891 iii 889:891 iii 889:891 Here, we show that i) both proteins interact, ii) epidermal growth factor like repeats 2 and 5 of DLL3 are O-fucosylated at consensus sites for POFUT1, and iii) further modified by FNG proteins in vitro. 25856312 7 63 with interaction 1166:1176 arg1 DLL1 1220:1223 full length Notch1or DLL1 1199:1223 full length Notch1or DLL1 1199:1223 Mutation of the O-fucosylation sites in DLL3 does not disrupt the interaction of DLL3 with LFNG or full length Notch1or DLL1, and O-fucosylation-deficient DLL3 can still inhibit Notch in cis in vitro. 25856312 7 63 with interaction 1166:1176 arg1 LFNG 1191:1194 LFNG 1191:1194 LFNG 1191:1194 Mutation of the O-fucosylation sites in DLL3 does not disrupt the interaction of DLL3 with LFNG or full length Notch1or DLL1, and O-fucosylation-deficient DLL3 can still inhibit Notch in cis in vitro. 25856312 2 64 theme Delta-like 194:203 arg1 DLL1 169:172 DLL1 169:172 DLL1 169:172 In contrast to DLL1 and DLL4, the other Delta-like proteins in the mouse, DLL3 does not bind in trans to Notch and does not activate the receptor, but shows cis-interaction and cis-inhibitory properties on Notch signaling in vitro. 25856312 2 64 theme Delta-like 194:203 arg1 proteins 205:212 the other Delta-like proteins 184:212 the other Delta-like proteins in the mouse 184:225 In contrast to DLL1 and DLL4, the other Delta-like proteins in the mouse, DLL3 does not bind in trans to Notch and does not activate the receptor, but shows cis-interaction and cis-inhibitory properties on Notch signaling in vitro. 25856312 7 65 theme length 1204:1209 arg1 DLL1 1220:1223 full length Notch1or DLL1 1199:1223 full length Notch1or DLL1 1199:1223 Mutation of the O-fucosylation sites in DLL3 does not disrupt the interaction of DLL3 with LFNG or full length Notch1or DLL1, and O-fucosylation-deficient DLL3 can still inhibit Notch in cis in vitro. 25856312 8 66 theme DLL3 1416:1419 arg1 loss 1397:1400 the loss 1393:1400 the loss of endogenous DLL3 during somitogenesis in the embryo 1393:1454 However, in contrast to wild type DLL3, O-fucosylation-deficient DLL3 cannot compensate for the loss of endogenous DLL3 during somitogenesis in the embryo. 25856312 2 67 theme other 188:192 arg1 DLL1 169:172 DLL1 169:172 DLL1 169:172 In contrast to DLL1 and DLL4, the other Delta-like proteins in the mouse, DLL3 does not bind in trans to Notch and does not activate the receptor, but shows cis-interaction and cis-inhibitory properties on Notch signaling in vitro. 25856312 2 67 theme other 188:192 arg1 proteins 205:212 the other Delta-like proteins 184:212 the other Delta-like proteins in the mouse 184:225 In contrast to DLL1 and DLL4, the other Delta-like proteins in the mouse, DLL3 does not bind in trans to Notch and does not activate the receptor, but shows cis-interaction and cis-inhibitory properties on Notch signaling in vitro. 25856312 1 68 from amniotes 144:151 arg1 family 117:122 the DSL family 109:122 the DSL family of Notch ligands in amniotes 109:151 Delta-like 3 (DLL3) is a member of the DSL family of Notch ligands in amniotes. 25856312 8 69 dep DLL3 1335:1338 arg1 contrast 1313:1320 contrast 1313:1320 contrast 1313:1320 However, in contrast to wild type DLL3, O-fucosylation-deficient DLL3 cannot compensate for the loss of endogenous DLL3 during somitogenesis in the embryo. 25856312 5 70 theme O-fucosylated 840:852 arg1 factor 800:805 epidermal growth factor 783:805 epidermal growth factor like repeats 2 and 5 of DLL3 783:834 Here, we show that i) both proteins interact, ii) epidermal growth factor like repeats 2 and 5 of DLL3 are O-fucosylated at consensus sites for POFUT1, and iii) further modified by FNG proteins in vitro. 25856312 5 70 theme O-fucosylated 840:852 arg1 sites 867:871 O-fucosylated at consensus sites 840:871 O-fucosylated at consensus sites for POFUT1 840:882 Here, we show that i) both proteins interact, ii) epidermal growth factor like repeats 2 and 5 of DLL3 are O-fucosylated at consensus sites for POFUT1, and iii) further modified by FNG proteins in vitro. 25856312 1 71 theme DSL 113:115 arg1 family 117:122 the DSL family 109:122 the DSL family of Notch ligands in amniotes 109:151 Delta-like 3 (DLL3) is a member of the DSL family of Notch ligands in amniotes. 25364905 7 0 theme anti-cancer 1445:1455 arg1 agent 1457:1461 an anti-cancer agent 1442:1461 an anti-cancer agent 1442:1461 As a lectin that binds specifically to a cancer-associated glycan, has potential to be developed as an anti-cancer agent. 25364905 4 1 theme SRL 859:861 arg1 binding 876:882 SRL cell surface binding 859:882 SRL cell surface binding 859:882 The inhibitory effect of SRL on cancer cell proliferation was shown to be a consequence of SRL cell surface binding and subsequent induction of cellular apoptosis, an effect that was largely prevented by the presence of inhibitors against caspases -3, -8, or -9. 25364905 4 2 theme surface 868:874 arg1 binding 876:882 SRL cell surface binding 859:882 SRL cell surface binding 859:882 The inhibitory effect of SRL on cancer cell proliferation was shown to be a consequence of SRL cell surface binding and subsequent induction of cellular apoptosis, an effect that was largely prevented by the presence of inhibitors against caspases -3, -8, or -9. 25364905 6 3 theme cancer 1235:1240 arg1 cells 1242:1246 human breast cancer cells 1222:1246 human breast cancer cells 1222:1246 In conclusion, SRL inhibits the growth of human breast cancer cells via induction of cell apoptosis but has substantially less effect on normal epithelial cells. 25364905 1 4 theme exquisite 271:279 arg1 specificity 289:299 exquisite binding specificity 271:299 exquisite binding specificity towards O-linked, Thomsen-Freidenreich (Galβ1-3GalNAcα1-Ser/Thr, TF) associated glycans 271:387 Sclerotium rolfsii lectin (SRL) isolated from the phytopathogenic fungus Sclerotium rolfsii has exquisite binding specificity towards O-linked, Thomsen-Freidenreich (Galβ1-3GalNAcα1-Ser/Thr, TF) associated glycans. 25364905 6 5 theme human 1222:1226 arg1 cells 1242:1246 human breast cancer cells 1222:1246 human breast cancer cells 1222:1246 In conclusion, SRL inhibits the growth of human breast cancer cells via induction of cell apoptosis but has substantially less effect on normal epithelial cells. 25364905 1 6 theme Sclerotium 175:184 arg1 rolfsii 186:192 Sclerotium rolfsii 175:192 Sclerotium rolfsii lectin (SRL) isolated from the phytopathogenic fungus Sclerotium rolfsii 175:265 Sclerotium rolfsii lectin (SRL) isolated from the phytopathogenic fungus Sclerotium rolfsii has exquisite binding specificity towards O-linked, Thomsen-Freidenreich (Galβ1-3GalNAcα1-Ser/Thr, TF) associated glycans. 25364905 5 7 theme intense 1142:1148 arg1 binding 1150:1156 intense binding 1142:1156 intense binding to cancerous tissues 1142:1177 Lectin histochemistry using biotin-labelled SRL showed little binding of SRL to normal human breast tissue but intense binding to cancerous tissues. 25364905 3 8 theme HMEC 756:759 arg1 cells 761:765 non-tumorigenic MCF-10A and HMEC cells 728:765 cells 761:765 SRL caused marked, dose-dependent, inhibition of proliferation of MCF-7 and ZR-75 cells but only weak inhibition of proliferation of non-tumorigenic MCF-10A and HMEC cells. 25364905 4 9 theme cellular 912:919 arg1 apoptosis 921:929 cellular apoptosis 912:929 cellular apoptosis 912:929 The inhibitory effect of SRL on cancer cell proliferation was shown to be a consequence of SRL cell surface binding and subsequent induction of cellular apoptosis, an effect that was largely prevented by the presence of inhibitors against caspases -3, -8, or -9. 25364905 4 9 theme cellular 912:919 arg1 effect 935:940 an effect 932:940 an effect that was largely prevented by the presence of inhibitors against caspases -3, -8, or -9 932:1028 The inhibitory effect of SRL on cancer cell proliferation was shown to be a consequence of SRL cell surface binding and subsequent induction of cellular apoptosis, an effect that was largely prevented by the presence of inhibitors against caspases -3, -8, or -9. 25364905 3 10 theme MCF-10A 744:750 arg1 proliferation 711:723 proliferation 711:723 proliferation of non-tumorigenic MCF-10A and HMEC cells 711:765 SRL caused marked, dose-dependent, inhibition of proliferation of MCF-7 and ZR-75 cells but only weak inhibition of proliferation of non-tumorigenic MCF-10A and HMEC cells. 25364905 0 11 theme mammary 118:124 arg1 cells 137:141 normal human mammary epithelial cells 105:141 normal human mammary epithelial cells 105:141 Sclerotium rolfsii lectin induces stronger inhibition of proliferation in human breast cancer cells than normal human mammary epithelial cells by induction of cell apoptosis. 25364905 5 12 theme Lectin 1031:1036 arg1 histochemistry 1038:1051 Lectin histochemistry 1031:1051 Lectin histochemistry using biotin-labelled SRL 1031:1077 Lectin histochemistry using biotin-labelled SRL showed little binding of SRL to normal human breast tissue but intense binding to cancerous tissues. 25364905 2 13 theme cells 580:584 arg1 proliferation 438:450 proliferation 438:450 proliferation of human breast cancer cells (MCF-7 and ZR-75), non-tumorigenic breast epithelial cells (MCF-10A) and normal mammary epithelial cells (HMECs) 438:592 This study investigated the influence of SRL on proliferation of human breast cancer cells (MCF-7 and ZR-75), non-tumorigenic breast epithelial cells (MCF-10A) and normal mammary epithelial cells (HMECs). 25364905 6 14 theme apoptosis 1270:1278 arg1 induction 1252:1260 induction 1252:1260 induction of cell apoptosis 1252:1278 In conclusion, SRL inhibits the growth of human breast cancer cells via induction of cell apoptosis but has substantially less effect on normal epithelial cells. 25364905 6 15 contain has 1284:1286 arg2 effect 1307:1312 substantially less effect 1288:1312 substantially less effect 1288:1312 In conclusion, SRL inhibits the growth of human breast cancer cells via induction of cell apoptosis but has substantially less effect on normal epithelial cells. 25364905 6 15 contain has 1284:1286 arg1 SRL 1195:1197 SRL 1195:1197 SRL 1195:1197 In conclusion, SRL inhibits the growth of human breast cancer cells via induction of cell apoptosis but has substantially less effect on normal epithelial cells. 25364905 4 16 theme induction 899:907 arg1 consequence 844:854 a consequence 842:854 a consequence of SRL cell surface binding and subsequent induction of cellular apoptosis, an effect that was largely prevented by the presence of inhibitors against caspases -3, -8, or -9 842:1028 The inhibitory effect of SRL on cancer cell proliferation was shown to be a consequence of SRL cell surface binding and subsequent induction of cellular apoptosis, an effect that was largely prevented by the presence of inhibitors against caspases -3, -8, or -9. 25364905 4 16 theme induction 899:907 arg1 effect 783:788 The inhibitory effect 768:788 The inhibitory effect of SRL on cancer cell proliferation 768:824 The inhibitory effect of SRL on cancer cell proliferation was shown to be a consequence of SRL cell surface binding and subsequent induction of cellular apoptosis, an effect that was largely prevented by the presence of inhibitors against caspases -3, -8, or -9. 25364905 0 17 theme cell 159:162 arg1 apoptosis 164:172 cell apoptosis 159:172 cell apoptosis 159:172 Sclerotium rolfsii lectin induces stronger inhibition of proliferation in human breast cancer cells than normal human mammary epithelial cells by induction of cell apoptosis. 25364905 1 18 contain has 267:269 arg1 SRL 202:204 SRL 202:204 SRL 202:204 Sclerotium rolfsii lectin (SRL) isolated from the phytopathogenic fungus Sclerotium rolfsii has exquisite binding specificity towards O-linked, Thomsen-Freidenreich (Galβ1-3GalNAcα1-Ser/Thr, TF) associated glycans. 25364905 1 18 contain has 267:269 arg1 lectin 194:199 Sclerotium rolfsii lectin 175:199 Sclerotium rolfsii lectin (SRL) isolated from the phytopathogenic fungus Sclerotium rolfsii 175:265 Sclerotium rolfsii lectin (SRL) isolated from the phytopathogenic fungus Sclerotium rolfsii has exquisite binding specificity towards O-linked, Thomsen-Freidenreich (Galβ1-3GalNAcα1-Ser/Thr, TF) associated glycans. 25364905 1 18 contain has 267:269 arg2 specificity 289:299 exquisite binding specificity 271:299 exquisite binding specificity towards O-linked, Thomsen-Freidenreich (Galβ1-3GalNAcα1-Ser/Thr, TF) associated glycans 271:387 Sclerotium rolfsii lectin (SRL) isolated from the phytopathogenic fungus Sclerotium rolfsii has exquisite binding specificity towards O-linked, Thomsen-Freidenreich (Galβ1-3GalNAcα1-Ser/Thr, TF) associated glycans. 25364905 2 19 theme breast 516:521 arg1 cells 534:538 non-tumorigenic breast epithelial cells 500:538 non-tumorigenic breast epithelial cells (MCF-10A) 500:548 This study investigated the influence of SRL on proliferation of human breast cancer cells (MCF-7 and ZR-75), non-tumorigenic breast epithelial cells (MCF-10A) and normal mammary epithelial cells (HMECs). 25364905 2 19 theme breast 516:521 arg1 MCF-10A 541:547 MCF-10A 541:547 MCF-10A 541:547 This study investigated the influence of SRL on proliferation of human breast cancer cells (MCF-7 and ZR-75), non-tumorigenic breast epithelial cells (MCF-10A) and normal mammary epithelial cells (HMECs). 25364905 0 20 from cells 94:98 arg1 inhibition 43:52 stronger inhibition 34:52 stronger inhibition of proliferation in human breast cancer cells than normal human mammary epithelial cells 34:141 Sclerotium rolfsii lectin induces stronger inhibition of proliferation in human breast cancer cells than normal human mammary epithelial cells by induction of cell apoptosis. 25364905 1 21 dep O-linked 309:316 arg1 Thomsen-Freidenreich 319:338 Thomsen-Freidenreich 319:338 Thomsen-Freidenreich 319:338 Sclerotium rolfsii lectin (SRL) isolated from the phytopathogenic fungus Sclerotium rolfsii has exquisite binding specificity towards O-linked, Thomsen-Freidenreich (Galβ1-3GalNAcα1-Ser/Thr, TF) associated glycans. 25364905 4 22 theme subsequent 888:897 arg1 induction 899:907 subsequent induction 888:907 subsequent induction of cellular apoptosis, an effect that was largely prevented by the presence of inhibitors against caspases -3, -8, or -9 888:1028 The inhibitory effect of SRL on cancer cell proliferation was shown to be a consequence of SRL cell surface binding and subsequent induction of cellular apoptosis, an effect that was largely prevented by the presence of inhibitors against caspases -3, -8, or -9. 25364905 0 23 theme breast 80:85 arg1 cells 94:98 human breast cancer cells 74:98 human breast cancer cells than normal human mammary epithelial cells 74:141 Sclerotium rolfsii lectin induces stronger inhibition of proliferation in human breast cancer cells than normal human mammary epithelial cells by induction of cell apoptosis. 25364905 4 24 from effect 783:788 arg1 proliferation 812:824 cancer cell proliferation 800:824 cancer cell proliferation 800:824 The inhibitory effect of SRL on cancer cell proliferation was shown to be a consequence of SRL cell surface binding and subsequent induction of cellular apoptosis, an effect that was largely prevented by the presence of inhibitors against caspases -3, -8, or -9. 25364905 6 25 theme epithelial 1324:1333 arg1 cells 1335:1339 normal epithelial cells 1317:1339 normal epithelial cells 1317:1339 In conclusion, SRL inhibits the growth of human breast cancer cells via induction of cell apoptosis but has substantially less effect on normal epithelial cells. 25364905 2 26 theme cells 534:538 arg1 proliferation 438:450 proliferation 438:450 proliferation of human breast cancer cells (MCF-7 and ZR-75), non-tumorigenic breast epithelial cells (MCF-10A) and normal mammary epithelial cells (HMECs) 438:592 This study investigated the influence of SRL on proliferation of human breast cancer cells (MCF-7 and ZR-75), non-tumorigenic breast epithelial cells (MCF-10A) and normal mammary epithelial cells (HMECs). 25364905 0 27 theme normal 105:110 arg1 cells 137:141 normal human mammary epithelial cells 105:141 normal human mammary epithelial cells 105:141 Sclerotium rolfsii lectin induces stronger inhibition of proliferation in human breast cancer cells than normal human mammary epithelial cells by induction of cell apoptosis. 25364905 5 28 theme little 1086:1091 arg1 binding 1093:1099 little binding 1086:1099 little binding of SRL to normal human breast tissue 1086:1136 Lectin histochemistry using biotin-labelled SRL showed little binding of SRL to normal human breast tissue but intense binding to cancerous tissues. 25364905 2 29 theme cells 475:479 arg1 proliferation 438:450 proliferation 438:450 proliferation of human breast cancer cells (MCF-7 and ZR-75), non-tumorigenic breast epithelial cells (MCF-10A) and normal mammary epithelial cells (HMECs) 438:592 This study investigated the influence of SRL on proliferation of human breast cancer cells (MCF-7 and ZR-75), non-tumorigenic breast epithelial cells (MCF-10A) and normal mammary epithelial cells (HMECs). 25364905 1 30 dep Thomsen-Freidenreich 319:338 arg1 TF 366:367 TF 366:367 TF 366:367 Sclerotium rolfsii lectin (SRL) isolated from the phytopathogenic fungus Sclerotium rolfsii has exquisite binding specificity towards O-linked, Thomsen-Freidenreich (Galβ1-3GalNAcα1-Ser/Thr, TF) associated glycans. 25364905 1 30 dep Thomsen-Freidenreich 319:338 arg1 Galβ1-3GalNAcα1-Ser/Thr 341:363 Galβ1-3GalNAcα1-Ser/Thr 341:363 Galβ1-3GalNAcα1-Ser/Thr 341:363 Sclerotium rolfsii lectin (SRL) isolated from the phytopathogenic fungus Sclerotium rolfsii has exquisite binding specificity towards O-linked, Thomsen-Freidenreich (Galβ1-3GalNAcα1-Ser/Thr, TF) associated glycans. 25364905 0 31 theme Sclerotium 0:9 arg1 rolfsii 11:17 Sclerotium rolfsii 0:17 Sclerotium rolfsii lectin 0:24 Sclerotium rolfsii lectin induces stronger inhibition of proliferation in human breast cancer cells than normal human mammary epithelial cells by induction of cell apoptosis. 25364905 1 32 theme binding 281:287 arg1 specificity 289:299 exquisite binding specificity 271:299 exquisite binding specificity towards O-linked, Thomsen-Freidenreich (Galβ1-3GalNAcα1-Ser/Thr, TF) associated glycans 271:387 Sclerotium rolfsii lectin (SRL) isolated from the phytopathogenic fungus Sclerotium rolfsii has exquisite binding specificity towards O-linked, Thomsen-Freidenreich (Galβ1-3GalNAcα1-Ser/Thr, TF) associated glycans. 25364905 2 33 theme breast 461:466 arg1 MCF-7 482:486 MCF-7 482:486 MCF-7 482:486 This study investigated the influence of SRL on proliferation of human breast cancer cells (MCF-7 and ZR-75), non-tumorigenic breast epithelial cells (MCF-10A) and normal mammary epithelial cells (HMECs). 25364905 2 33 theme breast 461:466 arg1 cells 475:479 human breast cancer cells 455:479 human breast cancer cells (MCF-7 and ZR-75) 455:497 This study investigated the influence of SRL on proliferation of human breast cancer cells (MCF-7 and ZR-75), non-tumorigenic breast epithelial cells (MCF-10A) and normal mammary epithelial cells (HMECs). 25364905 2 33 theme breast 461:466 arg1 ZR-75 492:496 ZR-75 492:496 ZR-75 492:496 This study investigated the influence of SRL on proliferation of human breast cancer cells (MCF-7 and ZR-75), non-tumorigenic breast epithelial cells (MCF-10A) and normal mammary epithelial cells (HMECs). 25364905 0 34 theme stronger 34:41 arg1 inhibition 43:52 stronger inhibition 34:52 stronger inhibition of proliferation in human breast cancer cells than normal human mammary epithelial cells 34:141 Sclerotium rolfsii lectin induces stronger inhibition of proliferation in human breast cancer cells than normal human mammary epithelial cells by induction of cell apoptosis. 25364905 5 35 theme human 1118:1122 arg1 tissue 1131:1136 normal human breast tissue 1111:1136 normal human breast tissue 1111:1136 Lectin histochemistry using biotin-labelled SRL showed little binding of SRL to normal human breast tissue but intense binding to cancerous tissues. 25364905 3 36 theme cells 677:681 arg1 proliferation 644:656 proliferation 644:656 proliferation of MCF-7 and ZR-75 cells 644:681 SRL caused marked, dose-dependent, inhibition of proliferation of MCF-7 and ZR-75 cells but only weak inhibition of proliferation of non-tumorigenic MCF-10A and HMEC cells. 25364905 4 37 theme SRL 793:795 arg1 consequence 844:854 a consequence 842:854 a consequence of SRL cell surface binding and subsequent induction of cellular apoptosis, an effect that was largely prevented by the presence of inhibitors against caspases -3, -8, or -9 842:1028 The inhibitory effect of SRL on cancer cell proliferation was shown to be a consequence of SRL cell surface binding and subsequent induction of cellular apoptosis, an effect that was largely prevented by the presence of inhibitors against caspases -3, -8, or -9. 25364905 4 37 theme SRL 793:795 arg1 effect 783:788 The inhibitory effect 768:788 The inhibitory effect of SRL on cancer cell proliferation 768:824 The inhibitory effect of SRL on cancer cell proliferation was shown to be a consequence of SRL cell surface binding and subsequent induction of cellular apoptosis, an effect that was largely prevented by the presence of inhibitors against caspases -3, -8, or -9. 25364905 4 38 theme cancer 800:805 arg1 proliferation 812:824 cancer cell proliferation 800:824 cancer cell proliferation 800:824 The inhibitory effect of SRL on cancer cell proliferation was shown to be a consequence of SRL cell surface binding and subsequent induction of cellular apoptosis, an effect that was largely prevented by the presence of inhibitors against caspases -3, -8, or -9. 25364905 1 39 link O-linked 309:316 arg1 glycans 381:387 O-linked, Thomsen-Freidenreich (Galβ1-3GalNAcα1-Ser/Thr, TF) associated glycans 309:387 O-linked, Thomsen-Freidenreich (Galβ1-3GalNAcα1-Ser/Thr, TF) associated glycans 309:387 Sclerotium rolfsii lectin (SRL) isolated from the phytopathogenic fungus Sclerotium rolfsii has exquisite binding specificity towards O-linked, Thomsen-Freidenreich (Galβ1-3GalNAcα1-Ser/Thr, TF) associated glycans. 25364905 1 40 theme phytopathogenic 225:239 arg1 rolfsii 259:265 the phytopathogenic fungus Sclerotium rolfsii 221:265 the phytopathogenic fungus Sclerotium rolfsii 221:265 Sclerotium rolfsii lectin (SRL) isolated from the phytopathogenic fungus Sclerotium rolfsii has exquisite binding specificity towards O-linked, Thomsen-Freidenreich (Galβ1-3GalNAcα1-Ser/Thr, TF) associated glycans. 25364905 0 41 theme apoptosis 164:172 arg1 induction 146:154 induction 146:154 induction of cell apoptosis 146:172 Sclerotium rolfsii lectin induces stronger inhibition of proliferation in human breast cancer cells than normal human mammary epithelial cells by induction of cell apoptosis. 25364905 2 42 theme mammary 561:567 arg1 cells 580:584 normal mammary epithelial cells 554:584 normal mammary epithelial cells (HMECs) 554:592 This study investigated the influence of SRL on proliferation of human breast cancer cells (MCF-7 and ZR-75), non-tumorigenic breast epithelial cells (MCF-10A) and normal mammary epithelial cells (HMECs). 25364905 2 42 theme mammary 561:567 arg1 HMECs 587:591 HMECs 587:591 HMECs 587:591 This study investigated the influence of SRL on proliferation of human breast cancer cells (MCF-7 and ZR-75), non-tumorigenic breast epithelial cells (MCF-10A) and normal mammary epithelial cells (HMECs). 25364905 1 43 theme Sclerotium 248:257 arg1 rolfsii 259:265 the phytopathogenic fungus Sclerotium rolfsii 221:265 the phytopathogenic fungus Sclerotium rolfsii 221:265 Sclerotium rolfsii lectin (SRL) isolated from the phytopathogenic fungus Sclerotium rolfsii has exquisite binding specificity towards O-linked, Thomsen-Freidenreich (Galβ1-3GalNAcα1-Ser/Thr, TF) associated glycans. 25364905 6 44 theme cells 1242:1246 arg1 growth 1212:1217 the growth 1208:1217 the growth of human breast cancer cells 1208:1246 In conclusion, SRL inhibits the growth of human breast cancer cells via induction of cell apoptosis but has substantially less effect on normal epithelial cells. 25364905 4 45 theme cell 863:866 arg1 binding 876:882 SRL cell surface binding 859:882 SRL cell surface binding 859:882 The inhibitory effect of SRL on cancer cell proliferation was shown to be a consequence of SRL cell surface binding and subsequent induction of cellular apoptosis, an effect that was largely prevented by the presence of inhibitors against caspases -3, -8, or -9. 25364905 3 46 theme non-tumorigenic 728:742 arg1 MCF-10A 744:750 non-tumorigenic MCF-10A and HMEC cells 728:765 MCF-10A 744:750 SRL caused marked, dose-dependent, inhibition of proliferation of MCF-7 and ZR-75 cells but only weak inhibition of proliferation of non-tumorigenic MCF-10A and HMEC cells. 25364905 6 47 theme breast 1228:1233 arg1 cells 1242:1246 human breast cancer cells 1222:1246 human breast cancer cells 1222:1246 In conclusion, SRL inhibits the growth of human breast cancer cells via induction of cell apoptosis but has substantially less effect on normal epithelial cells. 25364905 7 48 theme cancer-associated 1383:1399 arg1 glycan 1401:1406 a cancer-associated glycan 1381:1406 a cancer-associated glycan 1381:1406 As a lectin that binds specifically to a cancer-associated glycan, has potential to be developed as an anti-cancer agent. 25364905 3 49 theme proliferation 711:723 arg1 inhibition 697:706 only weak inhibition 687:706 only weak inhibition of proliferation of non-tumorigenic MCF-10A and HMEC cells 687:765 SRL caused marked, dose-dependent, inhibition of proliferation of MCF-7 and ZR-75 cells but only weak inhibition of proliferation of non-tumorigenic MCF-10A and HMEC cells. 25364905 1 50 theme rolfsii 186:192 arg1 SRL 202:204 SRL 202:204 SRL 202:204 Sclerotium rolfsii lectin (SRL) isolated from the phytopathogenic fungus Sclerotium rolfsii has exquisite binding specificity towards O-linked, Thomsen-Freidenreich (Galβ1-3GalNAcα1-Ser/Thr, TF) associated glycans. 25364905 1 50 theme rolfsii 186:192 arg1 lectin 194:199 Sclerotium rolfsii lectin 175:199 Sclerotium rolfsii lectin (SRL) isolated from the phytopathogenic fungus Sclerotium rolfsii 175:265 Sclerotium rolfsii lectin (SRL) isolated from the phytopathogenic fungus Sclerotium rolfsii has exquisite binding specificity towards O-linked, Thomsen-Freidenreich (Galβ1-3GalNAcα1-Ser/Thr, TF) associated glycans. 25364905 3 51 theme cells 761:765 arg1 proliferation 711:723 proliferation 711:723 proliferation of non-tumorigenic MCF-10A and HMEC cells 711:765 SRL caused marked, dose-dependent, inhibition of proliferation of MCF-7 and ZR-75 cells but only weak inhibition of proliferation of non-tumorigenic MCF-10A and HMEC cells. 25364905 0 52 theme epithelial 126:135 arg1 cells 137:141 normal human mammary epithelial cells 105:141 normal human mammary epithelial cells 105:141 Sclerotium rolfsii lectin induces stronger inhibition of proliferation in human breast cancer cells than normal human mammary epithelial cells by induction of cell apoptosis. 25364905 3 53 dep marked 606:611 arg1 dose-dependent 614:627 dose-dependent 614:627 dose-dependent 614:627 SRL caused marked, dose-dependent, inhibition of proliferation of MCF-7 and ZR-75 cells but only weak inhibition of proliferation of non-tumorigenic MCF-10A and HMEC cells. 25364905 2 54 theme normal 554:559 arg1 cells 580:584 normal mammary epithelial cells 554:584 normal mammary epithelial cells (HMECs) 554:592 This study investigated the influence of SRL on proliferation of human breast cancer cells (MCF-7 and ZR-75), non-tumorigenic breast epithelial cells (MCF-10A) and normal mammary epithelial cells (HMECs). 25364905 2 54 theme normal 554:559 arg1 HMECs 587:591 HMECs 587:591 HMECs 587:591 This study investigated the influence of SRL on proliferation of human breast cancer cells (MCF-7 and ZR-75), non-tumorigenic breast epithelial cells (MCF-10A) and normal mammary epithelial cells (HMECs). 25364905 4 55 theme apoptosis 921:929 arg1 binding 876:882 SRL cell surface binding 859:882 SRL cell surface binding 859:882 The inhibitory effect of SRL on cancer cell proliferation was shown to be a consequence of SRL cell surface binding and subsequent induction of cellular apoptosis, an effect that was largely prevented by the presence of inhibitors against caspases -3, -8, or -9. 25364905 4 55 theme apoptosis 921:929 arg1 induction 899:907 subsequent induction 888:907 subsequent induction of cellular apoptosis, an effect that was largely prevented by the presence of inhibitors against caspases -3, -8, or -9 888:1028 The inhibitory effect of SRL on cancer cell proliferation was shown to be a consequence of SRL cell surface binding and subsequent induction of cellular apoptosis, an effect that was largely prevented by the presence of inhibitors against caspases -3, -8, or -9. 25364905 5 56 theme biotin-labelled 1059:1073 arg1 SRL 1075:1077 biotin-labelled SRL 1059:1077 biotin-labelled SRL 1059:1077 Lectin histochemistry using biotin-labelled SRL showed little binding of SRL to normal human breast tissue but intense binding to cancerous tissues. 25364905 5 57 theme normal 1111:1116 arg1 tissue 1131:1136 normal human breast tissue 1111:1136 normal human breast tissue 1111:1136 Lectin histochemistry using biotin-labelled SRL showed little binding of SRL to normal human breast tissue but intense binding to cancerous tissues. 25364905 4 58 theme binding 876:882 arg1 consequence 844:854 a consequence 842:854 a consequence of SRL cell surface binding and subsequent induction of cellular apoptosis, an effect that was largely prevented by the presence of inhibitors against caspases -3, -8, or -9 842:1028 The inhibitory effect of SRL on cancer cell proliferation was shown to be a consequence of SRL cell surface binding and subsequent induction of cellular apoptosis, an effect that was largely prevented by the presence of inhibitors against caspases -3, -8, or -9. 25364905 4 58 theme binding 876:882 arg1 effect 783:788 The inhibitory effect 768:788 The inhibitory effect of SRL on cancer cell proliferation 768:824 The inhibitory effect of SRL on cancer cell proliferation was shown to be a consequence of SRL cell surface binding and subsequent induction of cellular apoptosis, an effect that was largely prevented by the presence of inhibitors against caspases -3, -8, or -9. 25364905 6 59 theme cell 1265:1268 arg1 apoptosis 1270:1278 cell apoptosis 1265:1278 cell apoptosis 1265:1278 In conclusion, SRL inhibits the growth of human breast cancer cells via induction of cell apoptosis but has substantially less effect on normal epithelial cells. 25364905 2 60 theme epithelial 569:578 arg1 cells 580:584 normal mammary epithelial cells 554:584 normal mammary epithelial cells (HMECs) 554:592 This study investigated the influence of SRL on proliferation of human breast cancer cells (MCF-7 and ZR-75), non-tumorigenic breast epithelial cells (MCF-10A) and normal mammary epithelial cells (HMECs). 25364905 2 60 theme epithelial 569:578 arg1 HMECs 587:591 HMECs 587:591 HMECs 587:591 This study investigated the influence of SRL on proliferation of human breast cancer cells (MCF-7 and ZR-75), non-tumorigenic breast epithelial cells (MCF-10A) and normal mammary epithelial cells (HMECs). 25364905 0 61 theme human 74:78 arg1 cells 94:98 human breast cancer cells 74:98 human breast cancer cells than normal human mammary epithelial cells 74:141 Sclerotium rolfsii lectin induces stronger inhibition of proliferation in human breast cancer cells than normal human mammary epithelial cells by induction of cell apoptosis. 25364905 3 62 theme marked 606:611 arg1 inhibition 630:639 marked, dose-dependent, inhibition 606:639 marked, dose-dependent, inhibition of proliferation of MCF-7 and ZR-75 cells 606:681 SRL caused marked, dose-dependent, inhibition of proliferation of MCF-7 and ZR-75 cells but only weak inhibition of proliferation of non-tumorigenic MCF-10A and HMEC cells. 25364905 2 63 theme non-tumorigenic 500:514 arg1 cells 534:538 non-tumorigenic breast epithelial cells 500:538 non-tumorigenic breast epithelial cells (MCF-10A) 500:548 This study investigated the influence of SRL on proliferation of human breast cancer cells (MCF-7 and ZR-75), non-tumorigenic breast epithelial cells (MCF-10A) and normal mammary epithelial cells (HMECs). 25364905 2 63 theme non-tumorigenic 500:514 arg1 MCF-10A 541:547 MCF-10A 541:547 MCF-10A 541:547 This study investigated the influence of SRL on proliferation of human breast cancer cells (MCF-7 and ZR-75), non-tumorigenic breast epithelial cells (MCF-10A) and normal mammary epithelial cells (HMECs). 25364905 0 64 theme cancer 87:92 arg1 cells 94:98 human breast cancer cells 74:98 human breast cancer cells than normal human mammary epithelial cells 74:141 Sclerotium rolfsii lectin induces stronger inhibition of proliferation in human breast cancer cells than normal human mammary epithelial cells by induction of cell apoptosis. 25364905 5 65 theme SRL 1104:1106 arg1 binding 1093:1099 little binding 1086:1099 little binding of SRL to normal human breast tissue 1086:1136 Lectin histochemistry using biotin-labelled SRL showed little binding of SRL to normal human breast tissue but intense binding to cancerous tissues. 25364905 6 66 theme less 1302:1305 arg1 effect 1307:1312 substantially less effect 1288:1312 substantially less effect 1288:1312 In conclusion, SRL inhibits the growth of human breast cancer cells via induction of cell apoptosis but has substantially less effect on normal epithelial cells. 25364905 1 67 attach isolated 207:214 arg1 rolfsii 259:265 the phytopathogenic fungus Sclerotium rolfsii 221:265 the phytopathogenic fungus Sclerotium rolfsii 221:265 Sclerotium rolfsii lectin (SRL) isolated from the phytopathogenic fungus Sclerotium rolfsii has exquisite binding specificity towards O-linked, Thomsen-Freidenreich (Galβ1-3GalNAcα1-Ser/Thr, TF) associated glycans. 25364905 1 67 attach isolated 207:214 arg2 SRL 202:204 SRL 202:204 SRL 202:204 Sclerotium rolfsii lectin (SRL) isolated from the phytopathogenic fungus Sclerotium rolfsii has exquisite binding specificity towards O-linked, Thomsen-Freidenreich (Galβ1-3GalNAcα1-Ser/Thr, TF) associated glycans. 25364905 1 67 attach isolated 207:214 arg2 lectin 194:199 Sclerotium rolfsii lectin 175:199 Sclerotium rolfsii lectin (SRL) isolated from the phytopathogenic fungus Sclerotium rolfsii 175:265 Sclerotium rolfsii lectin (SRL) isolated from the phytopathogenic fungus Sclerotium rolfsii has exquisite binding specificity towards O-linked, Thomsen-Freidenreich (Galβ1-3GalNAcα1-Ser/Thr, TF) associated glycans. 25364905 1 68 theme associated 370:379 arg1 glycans 381:387 O-linked, Thomsen-Freidenreich (Galβ1-3GalNAcα1-Ser/Thr, TF) associated glycans 309:387 O-linked, Thomsen-Freidenreich (Galβ1-3GalNAcα1-Ser/Thr, TF) associated glycans 309:387 Sclerotium rolfsii lectin (SRL) isolated from the phytopathogenic fungus Sclerotium rolfsii has exquisite binding specificity towards O-linked, Thomsen-Freidenreich (Galβ1-3GalNAcα1-Ser/Thr, TF) associated glycans. 25364905 0 69 from proliferation 57:69 arg1 cells 94:98 human breast cancer cells 74:98 human breast cancer cells than normal human mammary epithelial cells 74:141 Sclerotium rolfsii lectin induces stronger inhibition of proliferation in human breast cancer cells than normal human mammary epithelial cells by induction of cell apoptosis. 25364905 0 70 theme human 112:116 arg1 cells 137:141 normal human mammary epithelial cells 105:141 normal human mammary epithelial cells 105:141 Sclerotium rolfsii lectin induces stronger inhibition of proliferation in human breast cancer cells than normal human mammary epithelial cells by induction of cell apoptosis. 25364905 2 71 theme epithelial 523:532 arg1 cells 534:538 non-tumorigenic breast epithelial cells 500:538 non-tumorigenic breast epithelial cells (MCF-10A) 500:548 This study investigated the influence of SRL on proliferation of human breast cancer cells (MCF-7 and ZR-75), non-tumorigenic breast epithelial cells (MCF-10A) and normal mammary epithelial cells (HMECs). 25364905 2 71 theme epithelial 523:532 arg1 MCF-10A 541:547 MCF-10A 541:547 MCF-10A 541:547 This study investigated the influence of SRL on proliferation of human breast cancer cells (MCF-7 and ZR-75), non-tumorigenic breast epithelial cells (MCF-10A) and normal mammary epithelial cells (HMECs). 25364905 0 72 from inhibition 43:52 arg1 cells 94:98 human breast cancer cells 74:98 human breast cancer cells than normal human mammary epithelial cells 74:141 Sclerotium rolfsii lectin induces stronger inhibition of proliferation in human breast cancer cells than normal human mammary epithelial cells by induction of cell apoptosis. 25364905 4 73 theme inhibitory 772:781 arg1 consequence 844:854 a consequence 842:854 a consequence of SRL cell surface binding and subsequent induction of cellular apoptosis, an effect that was largely prevented by the presence of inhibitors against caspases -3, -8, or -9 842:1028 The inhibitory effect of SRL on cancer cell proliferation was shown to be a consequence of SRL cell surface binding and subsequent induction of cellular apoptosis, an effect that was largely prevented by the presence of inhibitors against caspases -3, -8, or -9. 25364905 4 73 theme inhibitory 772:781 arg1 effect 783:788 The inhibitory effect 768:788 The inhibitory effect of SRL on cancer cell proliferation 768:824 The inhibitory effect of SRL on cancer cell proliferation was shown to be a consequence of SRL cell surface binding and subsequent induction of cellular apoptosis, an effect that was largely prevented by the presence of inhibitors against caspases -3, -8, or -9. 25364905 6 74 theme normal 1317:1322 arg1 cells 1335:1339 normal epithelial cells 1317:1339 normal epithelial cells 1317:1339 In conclusion, SRL inhibits the growth of human breast cancer cells via induction of cell apoptosis but has substantially less effect on normal epithelial cells. 25364905 0 75 theme rolfsii 11:17 arg1 lectin 19:24 Sclerotium rolfsii lectin 0:24 Sclerotium rolfsii lectin 0:24 Sclerotium rolfsii lectin induces stronger inhibition of proliferation in human breast cancer cells than normal human mammary epithelial cells by induction of cell apoptosis. 25364905 2 76 dep cells 475:479 arg1 MCF-7 482:486 MCF-7 482:486 MCF-7 482:486 This study investigated the influence of SRL on proliferation of human breast cancer cells (MCF-7 and ZR-75), non-tumorigenic breast epithelial cells (MCF-10A) and normal mammary epithelial cells (HMECs). 25364905 2 76 dep cells 475:479 arg1 cells 475:479 human breast cancer cells 455:479 human breast cancer cells (MCF-7 and ZR-75) 455:497 This study investigated the influence of SRL on proliferation of human breast cancer cells (MCF-7 and ZR-75), non-tumorigenic breast epithelial cells (MCF-10A) and normal mammary epithelial cells (HMECs). 25364905 2 76 dep cells 475:479 arg1 ZR-75 492:496 ZR-75 492:496 ZR-75 492:496 This study investigated the influence of SRL on proliferation of human breast cancer cells (MCF-7 and ZR-75), non-tumorigenic breast epithelial cells (MCF-10A) and normal mammary epithelial cells (HMECs). 25364905 2 77 theme cancer 468:473 arg1 MCF-7 482:486 MCF-7 482:486 MCF-7 482:486 This study investigated the influence of SRL on proliferation of human breast cancer cells (MCF-7 and ZR-75), non-tumorigenic breast epithelial cells (MCF-10A) and normal mammary epithelial cells (HMECs). 25364905 2 77 theme cancer 468:473 arg1 cells 475:479 human breast cancer cells 455:479 human breast cancer cells (MCF-7 and ZR-75) 455:497 This study investigated the influence of SRL on proliferation of human breast cancer cells (MCF-7 and ZR-75), non-tumorigenic breast epithelial cells (MCF-10A) and normal mammary epithelial cells (HMECs). 25364905 2 77 theme cancer 468:473 arg1 ZR-75 492:496 ZR-75 492:496 ZR-75 492:496 This study investigated the influence of SRL on proliferation of human breast cancer cells (MCF-7 and ZR-75), non-tumorigenic breast epithelial cells (MCF-10A) and normal mammary epithelial cells (HMECs). 25364905 2 78 theme human 455:459 arg1 MCF-7 482:486 MCF-7 482:486 MCF-7 482:486 This study investigated the influence of SRL on proliferation of human breast cancer cells (MCF-7 and ZR-75), non-tumorigenic breast epithelial cells (MCF-10A) and normal mammary epithelial cells (HMECs). 25364905 2 78 theme human 455:459 arg1 cells 475:479 human breast cancer cells 455:479 human breast cancer cells (MCF-7 and ZR-75) 455:497 This study investigated the influence of SRL on proliferation of human breast cancer cells (MCF-7 and ZR-75), non-tumorigenic breast epithelial cells (MCF-10A) and normal mammary epithelial cells (HMECs). 25364905 2 78 theme human 455:459 arg1 ZR-75 492:496 ZR-75 492:496 ZR-75 492:496 This study investigated the influence of SRL on proliferation of human breast cancer cells (MCF-7 and ZR-75), non-tumorigenic breast epithelial cells (MCF-10A) and normal mammary epithelial cells (HMECs). 25364905 3 79 theme proliferation 644:656 arg1 inhibition 630:639 marked, dose-dependent, inhibition 606:639 marked, dose-dependent, inhibition of proliferation of MCF-7 and ZR-75 cells 606:681 SRL caused marked, dose-dependent, inhibition of proliferation of MCF-7 and ZR-75 cells but only weak inhibition of proliferation of non-tumorigenic MCF-10A and HMEC cells. 25364905 5 80 theme cancerous 1161:1169 arg1 tissues 1171:1177 cancerous tissues 1161:1177 cancerous tissues 1161:1177 Lectin histochemistry using biotin-labelled SRL showed little binding of SRL to normal human breast tissue but intense binding to cancerous tissues. 25364905 1 81 theme O-linked 309:316 arg1 glycans 381:387 O-linked, Thomsen-Freidenreich (Galβ1-3GalNAcα1-Ser/Thr, TF) associated glycans 309:387 O-linked, Thomsen-Freidenreich (Galβ1-3GalNAcα1-Ser/Thr, TF) associated glycans 309:387 Sclerotium rolfsii lectin (SRL) isolated from the phytopathogenic fungus Sclerotium rolfsii has exquisite binding specificity towards O-linked, Thomsen-Freidenreich (Galβ1-3GalNAcα1-Ser/Thr, TF) associated glycans. 25364905 4 82 theme cell 807:810 arg1 proliferation 812:824 cancer cell proliferation 800:824 cancer cell proliferation 800:824 The inhibitory effect of SRL on cancer cell proliferation was shown to be a consequence of SRL cell surface binding and subsequent induction of cellular apoptosis, an effect that was largely prevented by the presence of inhibitors against caspases -3, -8, or -9. 25364905 2 83 theme SRL 431:433 arg1 influence 418:426 the influence 414:426 the influence of SRL on proliferation of human breast cancer cells (MCF-7 and ZR-75), non-tumorigenic breast epithelial cells (MCF-10A) and normal mammary epithelial cells (HMECs) 414:592 This study investigated the influence of SRL on proliferation of human breast cancer cells (MCF-7 and ZR-75), non-tumorigenic breast epithelial cells (MCF-10A) and normal mammary epithelial cells (HMECs). 25364905 0 84 theme proliferation 57:69 arg1 inhibition 43:52 stronger inhibition 34:52 stronger inhibition of proliferation in human breast cancer cells than normal human mammary epithelial cells 34:141 Sclerotium rolfsii lectin induces stronger inhibition of proliferation in human breast cancer cells than normal human mammary epithelial cells by induction of cell apoptosis. 25364905 5 85 theme breast 1124:1129 arg1 tissue 1131:1136 normal human breast tissue 1111:1136 normal human breast tissue 1111:1136 Lectin histochemistry using biotin-labelled SRL showed little binding of SRL to normal human breast tissue but intense binding to cancerous tissues. 25364905 4 86 theme inhibitors 988:997 arg1 presence 976:983 the presence 972:983 the presence of inhibitors against caspases -3, -8, or -9 972:1028 The inhibitory effect of SRL on cancer cell proliferation was shown to be a consequence of SRL cell surface binding and subsequent induction of cellular apoptosis, an effect that was largely prevented by the presence of inhibitors against caspases -3, -8, or -9. 25364905 3 87 theme ZR-75 671:675 arg1 cells 677:681 MCF-7 and ZR-75 cells 661:681 MCF-7 and ZR-75 cells 661:681 SRL caused marked, dose-dependent, inhibition of proliferation of MCF-7 and ZR-75 cells but only weak inhibition of proliferation of non-tumorigenic MCF-10A and HMEC cells. 25364905 2 88 from influence 418:426 arg1 proliferation 438:450 proliferation 438:450 proliferation of human breast cancer cells (MCF-7 and ZR-75), non-tumorigenic breast epithelial cells (MCF-10A) and normal mammary epithelial cells (HMECs) 438:592 This study investigated the influence of SRL on proliferation of human breast cancer cells (MCF-7 and ZR-75), non-tumorigenic breast epithelial cells (MCF-10A) and normal mammary epithelial cells (HMECs). 25364905 3 89 theme MCF-7 661:665 arg1 cells 677:681 MCF-7 and ZR-75 cells 661:681 MCF-7 and ZR-75 cells 661:681 SRL caused marked, dose-dependent, inhibition of proliferation of MCF-7 and ZR-75 cells but only weak inhibition of proliferation of non-tumorigenic MCF-10A and HMEC cells. 25364905 3 90 theme weak 692:695 arg1 inhibition 697:706 only weak inhibition 687:706 only weak inhibition of proliferation of non-tumorigenic MCF-10A and HMEC cells 687:765 SRL caused marked, dose-dependent, inhibition of proliferation of MCF-7 and ZR-75 cells but only weak inhibition of proliferation of non-tumorigenic MCF-10A and HMEC cells. 25364905 1 91 theme fungus 241:246 arg1 rolfsii 259:265 the phytopathogenic fungus Sclerotium rolfsii 221:265 the phytopathogenic fungus Sclerotium rolfsii 221:265 Sclerotium rolfsii lectin (SRL) isolated from the phytopathogenic fungus Sclerotium rolfsii has exquisite binding specificity towards O-linked, Thomsen-Freidenreich (Galβ1-3GalNAcα1-Ser/Thr, TF) associated glycans. 25267734 3 0 theme cortex 443:448 arg1 proliferation 450:462 cortex proliferation 443:462 cortex proliferation 443:462 We here report that hydrogen peroxide induces cortex proliferation in the Arabidopsis root and that SPINDLY (SPY), an O-linked glucosamine acetyltransferase, regulates cortex proliferation by maintaining cellular redox homeostasis. 25267734 4 1 from STOMAGEN 732:739 arg1 ERECTA 693:698 the leucine-rich receptor kinase ERECTA 660:698 the leucine-rich receptor kinase ERECTA 660:698 We also found that mutation in the leucine-rich receptor kinase ERECTA and its putative peptide ligand STOMAGEN block the effect of hydrogen peroxide on root cortex proliferation. 25267734 0 2 theme cortex 71:76 arg1 proliferation 78:90 redox-mediated cortex proliferation 56:90 redox-mediated cortex proliferation 56:90 SPINDLY, ERECTA, and its ligand STOMAGEN have a role in redox-mediated cortex proliferation in the Arabidopsis root. 25267734 5 3 theme signaling 981:989 arg1 involvement 952:962 the involvement 948:962 the involvement of intercellular signaling 948:989 However, ERECTA and STOMAGEN are expressed in the vascular tissue, whereas extra cortex cells are produced from the endodermis, suggesting the involvement of intercellular signaling. 25267734 4 4 theme peptide 717:723 arg1 STOMAGEN 732:739 its putative peptide ligand STOMAGEN 704:739 its putative peptide ligand STOMAGEN 704:739 We also found that mutation in the leucine-rich receptor kinase ERECTA and its putative peptide ligand STOMAGEN block the effect of hydrogen peroxide on root cortex proliferation. 25267734 8 5 theme cortex 1323:1328 arg1 proliferation 1330:1342 redox-mediated cortex proliferation 1308:1342 redox-mediated cortex proliferation 1308:1342 The importance of redox-mediated cortex proliferation as a protective mechanism against oxidative stress is also discussed. 25267734 0 6 theme redox-mediated 56:69 arg1 proliferation 78:90 redox-mediated cortex proliferation 56:90 redox-mediated cortex proliferation 56:90 SPINDLY, ERECTA, and its ligand STOMAGEN have a role in redox-mediated cortex proliferation in the Arabidopsis root. 25267734 6 7 theme erecta 1099:1104 arg1 background 1113:1122 the erecta mutant background 1095:1122 the erecta mutant background 1095:1122 SPY appears to act downstream of ERECTA, because the spy mutation still caused cortex proliferation in the erecta mutant background. 25267734 4 8 theme putative 708:715 arg1 STOMAGEN 732:739 its putative peptide ligand STOMAGEN 704:739 its putative peptide ligand STOMAGEN 704:739 We also found that mutation in the leucine-rich receptor kinase ERECTA and its putative peptide ligand STOMAGEN block the effect of hydrogen peroxide on root cortex proliferation. 25267734 3 9 theme hydrogen 417:424 arg1 peroxide 426:433 hydrogen peroxide 417:433 hydrogen peroxide 417:433 We here report that hydrogen peroxide induces cortex proliferation in the Arabidopsis root and that SPINDLY (SPY), an O-linked glucosamine acetyltransferase, regulates cortex proliferation by maintaining cellular redox homeostasis. 25267734 3 10 theme Arabidopsis 471:481 arg1 root 483:486 the Arabidopsis root 467:486 the Arabidopsis root 467:486 We here report that hydrogen peroxide induces cortex proliferation in the Arabidopsis root and that SPINDLY (SPY), an O-linked glucosamine acetyltransferase, regulates cortex proliferation by maintaining cellular redox homeostasis. 25267734 4 11 theme cortex 787:792 arg1 proliferation 794:806 root cortex proliferation 782:806 root cortex proliferation 782:806 We also found that mutation in the leucine-rich receptor kinase ERECTA and its putative peptide ligand STOMAGEN block the effect of hydrogen peroxide on root cortex proliferation. 25267734 4 12 theme ligand 725:730 arg1 STOMAGEN 732:739 its putative peptide ligand STOMAGEN 704:739 its putative peptide ligand STOMAGEN 704:739 We also found that mutation in the leucine-rich receptor kinase ERECTA and its putative peptide ligand STOMAGEN block the effect of hydrogen peroxide on root cortex proliferation. 25267734 1 13 theme living 166:171 arg1 organisms 173:181 all living organisms 162:181 all living organisms 162:181 Reactive oxygen species (ROS) are harmful to all living organisms and therefore they must be removed to ensure normal growth and development. 25267734 5 14 theme intercellular 967:979 arg1 signaling 981:989 intercellular signaling 967:989 intercellular signaling 967:989 However, ERECTA and STOMAGEN are expressed in the vascular tissue, whereas extra cortex cells are produced from the endodermis, suggesting the involvement of intercellular signaling. 25267734 6 15 theme mutant 1106:1111 arg1 background 1113:1122 the erecta mutant background 1095:1122 the erecta mutant background 1095:1122 SPY appears to act downstream of ERECTA, because the spy mutation still caused cortex proliferation in the erecta mutant background. 25267734 5 16 theme extra 884:888 arg1 cells 897:901 extra cortex cells 884:901 extra cortex cells 884:901 However, ERECTA and STOMAGEN are expressed in the vascular tissue, whereas extra cortex cells are produced from the endodermis, suggesting the involvement of intercellular signaling. 25267734 1 17 theme normal 228:233 arg1 growth 235:240 growth 235:240 growth 235:240 Reactive oxygen species (ROS) are harmful to all living organisms and therefore they must be removed to ensure normal growth and development. 25267734 4 18 theme leucine-rich 664:675 arg1 ERECTA 693:698 the leucine-rich receptor kinase ERECTA 660:698 the leucine-rich receptor kinase ERECTA 660:698 We also found that mutation in the leucine-rich receptor kinase ERECTA and its putative peptide ligand STOMAGEN block the effect of hydrogen peroxide on root cortex proliferation. 25267734 4 19 theme kinase 686:691 arg1 ERECTA 693:698 the leucine-rich receptor kinase ERECTA 660:698 the leucine-rich receptor kinase ERECTA 660:698 We also found that mutation in the leucine-rich receptor kinase ERECTA and its putative peptide ligand STOMAGEN block the effect of hydrogen peroxide on root cortex proliferation. 25267734 3 20 theme cellular 601:608 arg1 homeostasis 616:626 cellular redox homeostasis 601:626 cellular redox homeostasis 601:626 We here report that hydrogen peroxide induces cortex proliferation in the Arabidopsis root and that SPINDLY (SPY), an O-linked glucosamine acetyltransferase, regulates cortex proliferation by maintaining cellular redox homeostasis. 25267734 2 21 theme response 377:384 arg1 mechanisms 330:339 the mechanisms 326:339 the mechanisms of ROS perception and developmental response in plants 326:394 ROS are also signaling molecules, but so far little is known about the mechanisms of ROS perception and developmental response in plants. 25267734 0 22 theme Arabidopsis 99:109 arg1 root 111:114 the Arabidopsis root 95:114 the Arabidopsis root 95:114 SPINDLY, ERECTA, and its ligand STOMAGEN have a role in redox-mediated cortex proliferation in the Arabidopsis root. 25267734 8 23 theme proliferation 1330:1342 arg1 importance 1294:1303 The importance 1290:1303 The importance of redox-mediated cortex proliferation as a protective mechanism against oxidative stress 1290:1393 The importance of redox-mediated cortex proliferation as a protective mechanism against oxidative stress is also discussed. 25267734 4 24 theme peroxide 770:777 arg1 effect 751:756 the effect 747:756 the effect of hydrogen peroxide on root cortex proliferation 747:806 We also found that mutation in the leucine-rich receptor kinase ERECTA and its putative peptide ligand STOMAGEN block the effect of hydrogen peroxide on root cortex proliferation. 25267734 7 25 theme novel 1247:1251 arg1 pathway 1253:1259 a novel pathway 1245:1259 a novel pathway for ROS signaling in plants 1245:1287 We therefore have not only gained insight into the mechanism by which SPY regulates root development but also uncovered a novel pathway for ROS signaling in plants. 25267734 2 26 theme developmental 363:375 arg1 response 377:384 developmental response 363:384 developmental response 363:384 ROS are also signaling molecules, but so far little is known about the mechanisms of ROS perception and developmental response in plants. 25267734 5 27 theme cortex 890:895 arg1 cells 897:901 extra cortex cells 884:901 extra cortex cells 884:901 However, ERECTA and STOMAGEN are expressed in the vascular tissue, whereas extra cortex cells are produced from the endodermis, suggesting the involvement of intercellular signaling. 25267734 5 28 dep expressed 842:850 arg1 whereas 876:882 whereas 876:882 whereas 876:882 However, ERECTA and STOMAGEN are expressed in the vascular tissue, whereas extra cortex cells are produced from the endodermis, suggesting the involvement of intercellular signaling. 25267734 2 29 theme perception 348:357 arg1 mechanisms 330:339 the mechanisms 326:339 the mechanisms of ROS perception and developmental response in plants 326:394 ROS are also signaling molecules, but so far little is known about the mechanisms of ROS perception and developmental response in plants. 25267734 0 30 from role 48:51 arg1 root 111:114 the Arabidopsis root 95:114 the Arabidopsis root 95:114 SPINDLY, ERECTA, and its ligand STOMAGEN have a role in redox-mediated cortex proliferation in the Arabidopsis root. 25267734 0 30 from role 48:51 arg1 proliferation 78:90 redox-mediated cortex proliferation 56:90 redox-mediated cortex proliferation 56:90 SPINDLY, ERECTA, and its ligand STOMAGEN have a role in redox-mediated cortex proliferation in the Arabidopsis root. 25267734 3 31 theme O-linked 515:522 arg1 SPINDLY 497:503 SPINDLY 497:503 SPINDLY (SPY) 497:509 We here report that hydrogen peroxide induces cortex proliferation in the Arabidopsis root and that SPINDLY (SPY), an O-linked glucosamine acetyltransferase, regulates cortex proliferation by maintaining cellular redox homeostasis. 25267734 3 31 theme O-linked 515:522 arg1 acetyltransferase 536:552 an O-linked glucosamine acetyltransferase 512:552 an O-linked glucosamine acetyltransferase 512:552 We here report that hydrogen peroxide induces cortex proliferation in the Arabidopsis root and that SPINDLY (SPY), an O-linked glucosamine acetyltransferase, regulates cortex proliferation by maintaining cellular redox homeostasis. 25267734 7 32 theme ROS 1265:1267 arg1 signaling 1269:1277 ROS signaling 1265:1277 ROS signaling in plants 1265:1287 We therefore have not only gained insight into the mechanism by which SPY regulates root development but also uncovered a novel pathway for ROS signaling in plants. 25267734 2 33 theme ROS 344:346 arg1 perception 348:357 ROS perception 344:357 ROS perception 344:357 ROS are also signaling molecules, but so far little is known about the mechanisms of ROS perception and developmental response in plants. 25267734 3 34 theme glucosamine 524:534 arg1 SPINDLY 497:503 SPINDLY 497:503 SPINDLY (SPY) 497:509 We here report that hydrogen peroxide induces cortex proliferation in the Arabidopsis root and that SPINDLY (SPY), an O-linked glucosamine acetyltransferase, regulates cortex proliferation by maintaining cellular redox homeostasis. 25267734 3 34 theme glucosamine 524:534 arg1 acetyltransferase 536:552 an O-linked glucosamine acetyltransferase 512:552 an O-linked glucosamine acetyltransferase 512:552 We here report that hydrogen peroxide induces cortex proliferation in the Arabidopsis root and that SPINDLY (SPY), an O-linked glucosamine acetyltransferase, regulates cortex proliferation by maintaining cellular redox homeostasis. 25267734 3 35 link O-linked 515:522 arg1 SPINDLY 497:503 SPINDLY 497:503 SPINDLY (SPY) 497:509 We here report that hydrogen peroxide induces cortex proliferation in the Arabidopsis root and that SPINDLY (SPY), an O-linked glucosamine acetyltransferase, regulates cortex proliferation by maintaining cellular redox homeostasis. 25267734 3 35 link O-linked 515:522 arg1 acetyltransferase 536:552 an O-linked glucosamine acetyltransferase 512:552 an O-linked glucosamine acetyltransferase 512:552 We here report that hydrogen peroxide induces cortex proliferation in the Arabidopsis root and that SPINDLY (SPY), an O-linked glucosamine acetyltransferase, regulates cortex proliferation by maintaining cellular redox homeostasis. 25267734 8 36 theme redox-mediated 1308:1321 arg1 proliferation 1330:1342 redox-mediated cortex proliferation 1308:1342 redox-mediated cortex proliferation 1308:1342 The importance of redox-mediated cortex proliferation as a protective mechanism against oxidative stress is also discussed. 25267734 4 37 theme root 782:785 arg1 proliferation 794:806 root cortex proliferation 782:806 root cortex proliferation 782:806 We also found that mutation in the leucine-rich receptor kinase ERECTA and its putative peptide ligand STOMAGEN block the effect of hydrogen peroxide on root cortex proliferation. 25267734 5 38 theme vascular 859:866 arg1 tissue 868:873 the vascular tissue 855:873 the vascular tissue 855:873 However, ERECTA and STOMAGEN are expressed in the vascular tissue, whereas extra cortex cells are produced from the endodermis, suggesting the involvement of intercellular signaling. 25267734 0 39 theme ligand 25:30 arg1 STOMAGEN 32:39 its ligand STOMAGEN 21:39 its ligand STOMAGEN 21:39 SPINDLY, ERECTA, and its ligand STOMAGEN have a role in redox-mediated cortex proliferation in the Arabidopsis root. 25267734 8 40 theme protective 1349:1358 arg1 mechanism 1360:1368 a protective mechanism 1347:1368 a protective mechanism against oxidative stress 1347:1393 The importance of redox-mediated cortex proliferation as a protective mechanism against oxidative stress is also discussed. 25267734 2 41 from mechanisms 330:339 arg1 plants 389:394 plants 389:394 plants 389:394 ROS are also signaling molecules, but so far little is known about the mechanisms of ROS perception and developmental response in plants. 25267734 6 42 theme cortex 1071:1076 arg1 proliferation 1078:1090 cortex proliferation 1071:1090 cortex proliferation 1071:1090 SPY appears to act downstream of ERECTA, because the spy mutation still caused cortex proliferation in the erecta mutant background. 25267734 8 43 theme oxidative 1378:1386 arg1 stress 1388:1393 oxidative stress 1378:1393 oxidative stress 1378:1393 The importance of redox-mediated cortex proliferation as a protective mechanism against oxidative stress is also discussed. 25267734 4 44 theme hydrogen 761:768 arg1 peroxide 770:777 hydrogen peroxide 761:777 hydrogen peroxide 761:777 We also found that mutation in the leucine-rich receptor kinase ERECTA and its putative peptide ligand STOMAGEN block the effect of hydrogen peroxide on root cortex proliferation. 25267734 4 45 theme receptor 677:684 arg1 ERECTA 693:698 the leucine-rich receptor kinase ERECTA 660:698 the leucine-rich receptor kinase ERECTA 660:698 We also found that mutation in the leucine-rich receptor kinase ERECTA and its putative peptide ligand STOMAGEN block the effect of hydrogen peroxide on root cortex proliferation. 25267734 7 46 from signaling 1269:1277 arg1 plants 1282:1287 plants 1282:1287 plants 1282:1287 We therefore have not only gained insight into the mechanism by which SPY regulates root development but also uncovered a novel pathway for ROS signaling in plants. 25267734 3 47 theme redox 610:614 arg1 homeostasis 616:626 cellular redox homeostasis 601:626 cellular redox homeostasis 601:626 We here report that hydrogen peroxide induces cortex proliferation in the Arabidopsis root and that SPINDLY (SPY), an O-linked glucosamine acetyltransferase, regulates cortex proliferation by maintaining cellular redox homeostasis. 25267734 3 48 theme cortex 565:570 arg1 proliferation 572:584 cortex proliferation 565:584 cortex proliferation 565:584 We here report that hydrogen peroxide induces cortex proliferation in the Arabidopsis root and that SPINDLY (SPY), an O-linked glucosamine acetyltransferase, regulates cortex proliferation by maintaining cellular redox homeostasis. 25267734 2 49 theme signaling 272:280 arg1 ROS 259:261 ROS 259:261 ROS 259:261 ROS are also signaling molecules, but so far little is known about the mechanisms of ROS perception and developmental response in plants. 25267734 2 49 theme signaling 272:280 arg1 molecules 282:290 signaling molecules 272:290 signaling molecules 272:290 ROS are also signaling molecules, but so far little is known about the mechanisms of ROS perception and developmental response in plants. 25267734 7 50 theme root 1209:1212 arg1 development 1214:1224 root development 1209:1224 root development 1209:1224 We therefore have not only gained insight into the mechanism by which SPY regulates root development but also uncovered a novel pathway for ROS signaling in plants. 25267734 6 51 theme spy 1045:1047 arg1 mutation 1049:1056 the spy mutation 1041:1056 the spy mutation 1041:1056 SPY appears to act downstream of ERECTA, because the spy mutation still caused cortex proliferation in the erecta mutant background. 25267734 4 52 from effect 751:756 arg1 proliferation 794:806 root cortex proliferation 782:806 root cortex proliferation 782:806 We also found that mutation in the leucine-rich receptor kinase ERECTA and its putative peptide ligand STOMAGEN block the effect of hydrogen peroxide on root cortex proliferation. 25267734 1 53 theme Reactive 117:124 arg1 ROS 142:144 ROS 142:144 ROS 142:144 Reactive oxygen species (ROS) are harmful to all living organisms and therefore they must be removed to ensure normal growth and development. 25267734 1 53 theme Reactive 117:124 arg1 species 133:139 Reactive oxygen species 117:139 Reactive oxygen species (ROS) 117:145 Reactive oxygen species (ROS) are harmful to all living organisms and therefore they must be removed to ensure normal growth and development. 25267734 0 54 contain have 41:44 arg1 ERECTA 9:14 ERECTA 9:14 ERECTA 9:14 SPINDLY, ERECTA, and its ligand STOMAGEN have a role in redox-mediated cortex proliferation in the Arabidopsis root. 25267734 0 54 contain have 41:44 arg1 SPINDLY 0:6 SPINDLY 0:6 SPINDLY 0:6 SPINDLY, ERECTA, and its ligand STOMAGEN have a role in redox-mediated cortex proliferation in the Arabidopsis root. 25267734 0 54 contain have 41:44 arg1 STOMAGEN 32:39 its ligand STOMAGEN 21:39 its ligand STOMAGEN 21:39 SPINDLY, ERECTA, and its ligand STOMAGEN have a role in redox-mediated cortex proliferation in the Arabidopsis root. 25267734 0 54 contain have 41:44 arg2 role 48:51 a role 46:51 a role in redox-mediated cortex proliferation in the Arabidopsis root 46:114 SPINDLY, ERECTA, and its ligand STOMAGEN have a role in redox-mediated cortex proliferation in the Arabidopsis root. 25267734 1 55 theme oxygen 126:131 arg1 ROS 142:144 ROS 142:144 ROS 142:144 Reactive oxygen species (ROS) are harmful to all living organisms and therefore they must be removed to ensure normal growth and development. 25267734 1 55 theme oxygen 126:131 arg1 species 133:139 Reactive oxygen species 117:139 Reactive oxygen species (ROS) 117:145 Reactive oxygen species (ROS) are harmful to all living organisms and therefore they must be removed to ensure normal growth and development. 25267734 4 56 from mutation 648:655 arg1 ERECTA 693:698 the leucine-rich receptor kinase ERECTA 660:698 the leucine-rich receptor kinase ERECTA 660:698 We also found that mutation in the leucine-rich receptor kinase ERECTA and its putative peptide ligand STOMAGEN block the effect of hydrogen peroxide on root cortex proliferation. 25228926 13 0 theme free 1831:1834 arg1 population 1820:1829 a young healthy adult population 1798:1829 a young healthy adult population free of any clinically relevant pathologies 1798:1873 O-GlcNAc has the potential to serve as a screening tool for predicting future metabolic disturbances in a young healthy adult population free of any clinically relevant pathologies. 25228926 9 1 located observed 1340:1347 arg2 expression 1325:1334 Greater O-GlcNAc expression 1308:1334 Greater O-GlcNAc expression 1308:1334 Greater O-GlcNAc expression was observed in the whole blood of HH compared to LH. 25228926 9 1 located observed 1340:1347 arg1 blood 1362:1366 the whole blood 1352:1366 the whole blood of HH compared to LH 1352:1387 Greater O-GlcNAc expression was observed in the whole blood of HH compared to LH. 25228926 7 2 dep quantified 971:980 arg1 triglycerides 1117:1129 triglycerides 1117:1129 triglycerides 1117:1129 O-GlcNAc and O-GlcNAc transferase (OGT) levels were quantified by immunoblotting and compared to anthropometric measures: body mass index (BMI), percentage body fat, aerobic fitness, blood glucose, triglycerides, HDL, insulin, and HbA1c. 25228926 7 2 dep quantified 971:980 arg1 BMI 1058:1060 BMI 1058:1060 BMI 1058:1060 O-GlcNAc and O-GlcNAc transferase (OGT) levels were quantified by immunoblotting and compared to anthropometric measures: body mass index (BMI), percentage body fat, aerobic fitness, blood glucose, triglycerides, HDL, insulin, and HbA1c. 25228926 7 2 dep quantified 971:980 arg1 HbA1c 1150:1154 HbA1c 1150:1154 HbA1c 1150:1154 O-GlcNAc and O-GlcNAc transferase (OGT) levels were quantified by immunoblotting and compared to anthropometric measures: body mass index (BMI), percentage body fat, aerobic fitness, blood glucose, triglycerides, HDL, insulin, and HbA1c. 25228926 7 2 dep quantified 971:980 arg1 fitness 1093:1099 aerobic fitness 1085:1099 aerobic fitness 1085:1099 O-GlcNAc and O-GlcNAc transferase (OGT) levels were quantified by immunoblotting and compared to anthropometric measures: body mass index (BMI), percentage body fat, aerobic fitness, blood glucose, triglycerides, HDL, insulin, and HbA1c. 25228926 7 2 dep quantified 971:980 arg1 HDL 1132:1134 HDL 1132:1134 HDL 1132:1134 O-GlcNAc and O-GlcNAc transferase (OGT) levels were quantified by immunoblotting and compared to anthropometric measures: body mass index (BMI), percentage body fat, aerobic fitness, blood glucose, triglycerides, HDL, insulin, and HbA1c. 25228926 7 2 dep quantified 971:980 arg1 insulin 1137:1143 insulin 1137:1143 insulin 1137:1143 O-GlcNAc and O-GlcNAc transferase (OGT) levels were quantified by immunoblotting and compared to anthropometric measures: body mass index (BMI), percentage body fat, aerobic fitness, blood glucose, triglycerides, HDL, insulin, and HbA1c. 25228926 7 2 dep quantified 971:980 arg1 fat 1080:1082 percentage body fat 1064:1082 percentage body fat 1064:1082 O-GlcNAc and O-GlcNAc transferase (OGT) levels were quantified by immunoblotting and compared to anthropometric measures: body mass index (BMI), percentage body fat, aerobic fitness, blood glucose, triglycerides, HDL, insulin, and HbA1c. 25228926 7 2 dep quantified 971:980 arg1 glucose 1108:1114 blood glucose 1102:1114 blood glucose 1102:1114 O-GlcNAc and O-GlcNAc transferase (OGT) levels were quantified by immunoblotting and compared to anthropometric measures: body mass index (BMI), percentage body fat, aerobic fitness, blood glucose, triglycerides, HDL, insulin, and HbA1c. 25228926 7 2 dep quantified 971:980 arg1 index 1051:1055 body mass index 1041:1055 body mass index (BMI) 1041:1061 O-GlcNAc and O-GlcNAc transferase (OGT) levels were quantified by immunoblotting and compared to anthropometric measures: body mass index (BMI), percentage body fat, aerobic fitness, blood glucose, triglycerides, HDL, insulin, and HbA1c. 25228926 5 3 theme Young 643:647 arg1 AIMMY 656:660 AIMMY 656:660 AIMMY 656:660 Healthy, young males (18-35 y) from the Assessing Inherited Metabolic syndrome Markers in the Young study (AIMMY), were divided into low (LH,0.60) or high (HH,1.61) homeostatic model assessment of insulin resistance (HOMA-IR) cohorts. 25228926 5 3 theme Young 643:647 arg1 study 649:653 the Young study 639:653 the Young study (AIMMY) 639:661 Healthy, young males (18-35 y) from the Assessing Inherited Metabolic syndrome Markers in the Young study (AIMMY), were divided into low (LH,0.60) or high (HH,1.61) homeostatic model assessment of insulin resistance (HOMA-IR) cohorts. 25228926 9 4 theme Greater 1308:1314 arg1 expression 1325:1334 Greater O-GlcNAc expression 1308:1334 Greater O-GlcNAc expression 1308:1334 Greater O-GlcNAc expression was observed in the whole blood of HH compared to LH. 25228926 12 5 theme metabolic 1639:1647 arg1 status 1649:1654 metabolic status 1639:1654 metabolic status 1639:1654 CONCLUSIONS Results indicate that O-GlcNAc has a greater sensitivity to metabolic status compared to HbA1c in this population. 25228926 5 6 theme Inherited 599:607 arg1 syndrome 619:626 the Assessing Inherited Metabolic syndrome 585:626 the Assessing Inherited Metabolic syndrome Markers in the Young study (AIMMY) 585:661 Healthy, young males (18-35 y) from the Assessing Inherited Metabolic syndrome Markers in the Young study (AIMMY), were divided into low (LH,0.60) or high (HH,1.61) homeostatic model assessment of insulin resistance (HOMA-IR) cohorts. 25228926 13 7 theme young 1800:1804 arg1 population 1820:1829 a young healthy adult population 1798:1829 a young healthy adult population free of any clinically relevant pathologies 1798:1873 O-GlcNAc has the potential to serve as a screening tool for predicting future metabolic disturbances in a young healthy adult population free of any clinically relevant pathologies. 25228926 0 8 theme O-GlcNAc 0:7 arg1 modification 9:20 O-GlcNAc modification 0:20 O-GlcNAc modification 0:20 O-GlcNAc modification is associated with insulin sensitivity in the whole blood of healthy young adult males. 25228926 1 9 theme predominant 151:161 arg1 tool 174:177 the predominant diagnostic tool 147:177 the predominant diagnostic tool for diabetes diagnosis and progression 147:216 BACKGROUND Hemoglobin A1c (HbA1c) is the predominant diagnostic tool for diabetes diagnosis and progression. 25228926 1 9 theme predominant 151:161 arg1 A1c 132:134 BACKGROUND Hemoglobin A1c 110:134 BACKGROUND Hemoglobin A1c (HbA1c) 110:142 BACKGROUND Hemoglobin A1c (HbA1c) is the predominant diagnostic tool for diabetes diagnosis and progression. 25228926 5 10 theme syndrome 619:626 arg1 Markers 628:634 the Assessing Inherited Metabolic syndrome Markers 585:634 the Assessing Inherited Metabolic syndrome Markers in the Young study (AIMMY) 585:661 Healthy, young males (18-35 y) from the Assessing Inherited Metabolic syndrome Markers in the Young study (AIMMY), were divided into low (LH,0.60) or high (HH,1.61) homeostatic model assessment of insulin resistance (HOMA-IR) cohorts. 25228926 13 11 theme adult 1814:1818 arg1 population 1820:1829 a young healthy adult population 1798:1829 a young healthy adult population free of any clinically relevant pathologies 1798:1873 O-GlcNAc has the potential to serve as a screening tool for predicting future metabolic disturbances in a young healthy adult population free of any clinically relevant pathologies. 25228926 7 12 theme anthropometric 1016:1029 arg1 measures 1031:1038 anthropometric measures 1016:1038 anthropometric measures 1016:1038 O-GlcNAc and O-GlcNAc transferase (OGT) levels were quantified by immunoblotting and compared to anthropometric measures: body mass index (BMI), percentage body fat, aerobic fitness, blood glucose, triglycerides, HDL, insulin, and HbA1c. 25228926 2 13 theme threshold 276:284 arg1 values 286:291 pre-diabetic threshold values 263:291 pre-diabetic threshold values 263:291 However, it has proven to be insensitive at pre-diabetic threshold values. 25228926 1 14 theme diabetes 183:190 arg1 diagnosis 192:200 diabetes diagnosis 183:200 diabetes diagnosis 183:200 BACKGROUND Hemoglobin A1c (HbA1c) is the predominant diagnostic tool for diabetes diagnosis and progression. 25228926 1 15 theme BACKGROUND 110:119 arg1 HbA1c 137:141 HbA1c 137:141 HbA1c 137:141 BACKGROUND Hemoglobin A1c (HbA1c) is the predominant diagnostic tool for diabetes diagnosis and progression. 25228926 1 15 theme BACKGROUND 110:119 arg1 A1c 132:134 BACKGROUND Hemoglobin A1c 110:134 BACKGROUND Hemoglobin A1c (HbA1c) 110:142 BACKGROUND Hemoglobin A1c (HbA1c) is the predominant diagnostic tool for diabetes diagnosis and progression. 25228926 1 15 theme BACKGROUND 110:119 arg1 tool 174:177 the predominant diagnostic tool 147:177 the predominant diagnostic tool for diabetes diagnosis and progression 147:216 BACKGROUND Hemoglobin A1c (HbA1c) is the predominant diagnostic tool for diabetes diagnosis and progression. 25228926 6 16 theme global 881:886 arg1 O-GlcNAc 896:903 whole blood global protein O-GlcNAc 869:903 whole blood global protein O-GlcNAc 869:903 FINDINGS The relationships between a panel of anthropometric, metabolic measures and whole blood global protein O-GlcNAc was examined. 25228926 4 17 theme O-GlcNAc 447:454 arg1 expression 456:465 O-GlcNAc expression 447:465 O-GlcNAc expression 447:465 The purpose of this study was to explore the sensitivity of O-GlcNAc expression as a potential marker of early metabolic dysfunction in a young adult population. 25228926 5 18 theme Healthy 549:555 arg1 males 564:568 Healthy, young males 549:568 Healthy, young males (18-35 y) 549:578 Healthy, young males (18-35 y) from the Assessing Inherited Metabolic syndrome Markers in the Young study (AIMMY), were divided into low (LH,0.60) or high (HH,1.61) homeostatic model assessment of insulin resistance (HOMA-IR) cohorts. 25228926 5 18 theme Healthy 549:555 arg1 y 577:577 18-35 y 571:577 18-35 y 571:577 Healthy, young males (18-35 y) from the Assessing Inherited Metabolic syndrome Markers in the Young study (AIMMY), were divided into low (LH,0.60) or high (HH,1.61) homeostatic model assessment of insulin resistance (HOMA-IR) cohorts. 25228926 9 19 theme HH 1371:1372 arg1 blood 1362:1366 the whole blood 1352:1366 the whole blood of HH compared to LH 1352:1387 Greater O-GlcNAc expression was observed in the whole blood of HH compared to LH. 25228926 6 20 theme whole 869:873 arg1 O-GlcNAc 896:903 whole blood global protein O-GlcNAc 869:903 whole blood global protein O-GlcNAc 869:903 FINDINGS The relationships between a panel of anthropometric, metabolic measures and whole blood global protein O-GlcNAc was examined. 25228926 5 21 dep low 682:684 arg1 LH,0.60 687:693 LH,0.60 687:693 LH,0.60 687:693 Healthy, young males (18-35 y) from the Assessing Inherited Metabolic syndrome Markers in the Young study (AIMMY), were divided into low (LH,0.60) or high (HH,1.61) homeostatic model assessment of insulin resistance (HOMA-IR) cohorts. 25228926 7 22 theme O-GlcNAc 932:939 arg1 OGT 954:956 OGT 954:956 OGT 954:956 O-GlcNAc and O-GlcNAc transferase (OGT) levels were quantified by immunoblotting and compared to anthropometric measures: body mass index (BMI), percentage body fat, aerobic fitness, blood glucose, triglycerides, HDL, insulin, and HbA1c. 25228926 7 22 theme O-GlcNAc 932:939 arg1 transferase 941:951 O-GlcNAc transferase 932:951 O-GlcNAc transferase (OGT) 932:957 O-GlcNAc and O-GlcNAc transferase (OGT) levels were quantified by immunoblotting and compared to anthropometric measures: body mass index (BMI), percentage body fat, aerobic fitness, blood glucose, triglycerides, HDL, insulin, and HbA1c. 25228926 13 23 contain has 1703:1705 arg2 potential 1711:1719 the potential to serve as a screening tool for predicting future metabolic disturbances in a young healthy adult population free of any clinically relevant pathologies 1707:1873 the potential to serve as a screening tool for predicting future metabolic disturbances in a young healthy adult population free of any clinically relevant pathologies 1707:1873 O-GlcNAc has the potential to serve as a screening tool for predicting future metabolic disturbances in a young healthy adult population free of any clinically relevant pathologies. 25228926 13 23 contain has 1703:1705 arg1 O-GlcNAc 1694:1701 O-GlcNAc 1694:1701 O-GlcNAc 1694:1701 O-GlcNAc has the potential to serve as a screening tool for predicting future metabolic disturbances in a young healthy adult population free of any clinically relevant pathologies. 25228926 5 24 theme high 699:702 arg1 assessment 732:741 low (LH,0.60) or high (HH,1.61) homeostatic model assessment 682:741 low (LH,0.60) or high (HH,1.61) homeostatic model assessment of insulin resistance (HOMA-IR) cohorts 682:781 Healthy, young males (18-35 y) from the Assessing Inherited Metabolic syndrome Markers in the Young study (AIMMY), were divided into low (LH,0.60) or high (HH,1.61) homeostatic model assessment of insulin resistance (HOMA-IR) cohorts. 25228926 7 25 theme O-GlcNAc 919:926 arg1 levels 959:964 O-GlcNAc and O-GlcNAc transferase (OGT) levels 919:964 O-GlcNAc and O-GlcNAc transferase (OGT) levels 919:964 O-GlcNAc and O-GlcNAc transferase (OGT) levels were quantified by immunoblotting and compared to anthropometric measures: body mass index (BMI), percentage body fat, aerobic fitness, blood glucose, triglycerides, HDL, insulin, and HbA1c. 25228926 2 26 from values 286:291 arg1 insensitive 248:258 insensitive 248:258 insensitive 248:258 However, it has proven to be insensitive at pre-diabetic threshold values. 25228926 4 27 theme metabolic 498:506 arg1 dysfunction 508:518 early metabolic dysfunction 492:518 early metabolic dysfunction 492:518 The purpose of this study was to explore the sensitivity of O-GlcNAc expression as a potential marker of early metabolic dysfunction in a young adult population. 25228926 13 28 theme future 1765:1770 arg1 disturbances 1782:1793 future metabolic disturbances 1765:1793 future metabolic disturbances 1765:1793 O-GlcNAc has the potential to serve as a screening tool for predicting future metabolic disturbances in a young healthy adult population free of any clinically relevant pathologies. 25228926 0 29 theme healthy 83:89 arg1 males 103:107 healthy young adult males 83:107 healthy young adult males 83:107 O-GlcNAc modification is associated with insulin sensitivity in the whole blood of healthy young adult males. 25228926 0 30 from sensitivity 49:59 arg1 blood 74:78 the whole blood 64:78 the whole blood of healthy young adult males 64:107 O-GlcNAc modification is associated with insulin sensitivity in the whole blood of healthy young adult males. 25228926 0 31 theme adult 97:101 arg1 males 103:107 healthy young adult males 83:107 healthy young adult males 83:107 O-GlcNAc modification is associated with insulin sensitivity in the whole blood of healthy young adult males. 25228926 7 32 theme body 1075:1078 arg1 fat 1080:1082 percentage body fat 1064:1082 percentage body fat 1064:1082 O-GlcNAc and O-GlcNAc transferase (OGT) levels were quantified by immunoblotting and compared to anthropometric measures: body mass index (BMI), percentage body fat, aerobic fitness, blood glucose, triglycerides, HDL, insulin, and HbA1c. 25228926 4 33 theme potential 472:480 arg1 marker 482:487 a potential marker 470:487 a potential marker of early metabolic dysfunction 470:518 The purpose of this study was to explore the sensitivity of O-GlcNAc expression as a potential marker of early metabolic dysfunction in a young adult population. 25228926 4 33 theme potential 472:480 arg1 sensitivity 432:442 the sensitivity 428:442 the sensitivity of O-GlcNAc expression 428:465 The purpose of this study was to explore the sensitivity of O-GlcNAc expression as a potential marker of early metabolic dysfunction in a young adult population. 25228926 8 34 theme body 1251:1254 arg1 fat 1256:1258 percent body fat 1243:1258 percent body fat 1243:1258 HOMA-IR cohorts showed no differences in BMI, blood glucose or HbA1c, but differed in percent body fat, plasma triglycerides, and circulating insulin. 25228926 13 35 theme screening 1735:1743 arg1 tool 1745:1748 a screening tool 1733:1748 a screening tool for predicting future metabolic disturbances in a young healthy adult population free of any clinically relevant pathologies 1733:1873 O-GlcNAc has the potential to serve as a screening tool for predicting future metabolic disturbances in a young healthy adult population free of any clinically relevant pathologies. 25228926 5 36 theme insulin 746:752 arg1 HOMA-IR 766:772 HOMA-IR 766:772 HOMA-IR 766:772 Healthy, young males (18-35 y) from the Assessing Inherited Metabolic syndrome Markers in the Young study (AIMMY), were divided into low (LH,0.60) or high (HH,1.61) homeostatic model assessment of insulin resistance (HOMA-IR) cohorts. 25228926 5 36 theme insulin 746:752 arg1 resistance 754:763 insulin resistance 746:763 insulin resistance (HOMA-IR) cohorts 746:781 Healthy, young males (18-35 y) from the Assessing Inherited Metabolic syndrome Markers in the Young study (AIMMY), were divided into low (LH,0.60) or high (HH,1.61) homeostatic model assessment of insulin resistance (HOMA-IR) cohorts. 25228926 7 37 theme body 1041:1044 arg1 BMI 1058:1060 BMI 1058:1060 BMI 1058:1060 O-GlcNAc and O-GlcNAc transferase (OGT) levels were quantified by immunoblotting and compared to anthropometric measures: body mass index (BMI), percentage body fat, aerobic fitness, blood glucose, triglycerides, HDL, insulin, and HbA1c. 25228926 7 37 theme body 1041:1044 arg1 index 1051:1055 body mass index 1041:1055 body mass index (BMI) 1041:1061 O-GlcNAc and O-GlcNAc transferase (OGT) levels were quantified by immunoblotting and compared to anthropometric measures: body mass index (BMI), percentage body fat, aerobic fitness, blood glucose, triglycerides, HDL, insulin, and HbA1c. 25228926 3 38 theme sensitive 366:374 arg1 biomarker 376:384 a sensitive biomarker 364:384 a sensitive biomarker 364:384 O-linked-β-N-acetylglucosamine (O-GlcNAc) modification has emerged as a sensitive biomarker. 25228926 7 39 theme aerobic 1085:1091 arg1 fitness 1093:1099 aerobic fitness 1085:1099 aerobic fitness 1085:1099 O-GlcNAc and O-GlcNAc transferase (OGT) levels were quantified by immunoblotting and compared to anthropometric measures: body mass index (BMI), percentage body fat, aerobic fitness, blood glucose, triglycerides, HDL, insulin, and HbA1c. 25228926 5 40 theme homeostatic 714:724 arg1 assessment 732:741 low (LH,0.60) or high (HH,1.61) homeostatic model assessment 682:741 low (LH,0.60) or high (HH,1.61) homeostatic model assessment of insulin resistance (HOMA-IR) cohorts 682:781 Healthy, young males (18-35 y) from the Assessing Inherited Metabolic syndrome Markers in the Young study (AIMMY), were divided into low (LH,0.60) or high (HH,1.61) homeostatic model assessment of insulin resistance (HOMA-IR) cohorts. 25228926 6 41 dep FINDINGS 784:791 arg1 relationships 797:809 The relationships 793:809 The relationships between a panel of anthropometric 793:843 FINDINGS The relationships between a panel of anthropometric, metabolic measures and whole blood global protein O-GlcNAc was examined. 25228926 11 42 theme OGT 1551:1553 arg1 expression 1555:1564 OGT expression 1551:1564 OGT expression 1551:1564 This effect was not related to OGT expression. 25228926 7 43 theme percentage 1064:1073 arg1 fat 1080:1082 percentage body fat 1064:1082 percentage body fat 1064:1082 O-GlcNAc and O-GlcNAc transferase (OGT) levels were quantified by immunoblotting and compared to anthropometric measures: body mass index (BMI), percentage body fat, aerobic fitness, blood glucose, triglycerides, HDL, insulin, and HbA1c. 25228926 5 44 from Markers 628:634 arg1 AIMMY 656:660 AIMMY 656:660 AIMMY 656:660 Healthy, young males (18-35 y) from the Assessing Inherited Metabolic syndrome Markers in the Young study (AIMMY), were divided into low (LH,0.60) or high (HH,1.61) homeostatic model assessment of insulin resistance (HOMA-IR) cohorts. 25228926 5 44 from Markers 628:634 arg1 study 649:653 the Young study 639:653 the Young study (AIMMY) 639:661 Healthy, young males (18-35 y) from the Assessing Inherited Metabolic syndrome Markers in the Young study (AIMMY), were divided into low (LH,0.60) or high (HH,1.61) homeostatic model assessment of insulin resistance (HOMA-IR) cohorts. 25228926 5 44 from Markers 628:634 arg1 males 564:568 Healthy, young males 549:568 Healthy, young males (18-35 y) 549:578 Healthy, young males (18-35 y) from the Assessing Inherited Metabolic syndrome Markers in the Young study (AIMMY), were divided into low (LH,0.60) or high (HH,1.61) homeostatic model assessment of insulin resistance (HOMA-IR) cohorts. 25228926 5 44 from Markers 628:634 arg1 y 577:577 18-35 y 571:577 18-35 y 571:577 Healthy, young males (18-35 y) from the Assessing Inherited Metabolic syndrome Markers in the Young study (AIMMY), were divided into low (LH,0.60) or high (HH,1.61) homeostatic model assessment of insulin resistance (HOMA-IR) cohorts. 25228926 7 45 theme mass 1046:1049 arg1 BMI 1058:1060 BMI 1058:1060 BMI 1058:1060 O-GlcNAc and O-GlcNAc transferase (OGT) levels were quantified by immunoblotting and compared to anthropometric measures: body mass index (BMI), percentage body fat, aerobic fitness, blood glucose, triglycerides, HDL, insulin, and HbA1c. 25228926 7 45 theme mass 1046:1049 arg1 index 1051:1055 body mass index 1041:1055 body mass index (BMI) 1041:1061 O-GlcNAc and O-GlcNAc transferase (OGT) levels were quantified by immunoblotting and compared to anthropometric measures: body mass index (BMI), percentage body fat, aerobic fitness, blood glucose, triglycerides, HDL, insulin, and HbA1c. 25228926 4 46 theme young 525:529 arg1 population 537:546 a young adult population 523:546 a young adult population 523:546 The purpose of this study was to explore the sensitivity of O-GlcNAc expression as a potential marker of early metabolic dysfunction in a young adult population. 25228926 13 47 theme pathologies 1863:1873 arg1 free 1831:1834 free 1831:1834 free 1831:1834 O-GlcNAc has the potential to serve as a screening tool for predicting future metabolic disturbances in a young healthy adult population free of any clinically relevant pathologies. 25228926 10 48 theme positive 1402:1409 arg1 association 1411:1421 a positive association 1400:1421 a positive association between HOMA-IR and O-GlcNAc 1400:1450 Moreover, a positive association between HOMA-IR and O-GlcNAc emerged, while no relationship was found between HbA1c and HOMA-IR. 25228926 6 49 theme metabolic 846:854 arg1 measures 856:863 metabolic measures 846:863 metabolic measures 846:863 FINDINGS The relationships between a panel of anthropometric, metabolic measures and whole blood global protein O-GlcNAc was examined. 25228926 2 50 theme pre-diabetic 263:274 arg1 values 286:291 pre-diabetic threshold values 263:291 pre-diabetic threshold values 263:291 However, it has proven to be insensitive at pre-diabetic threshold values. 25228926 6 51 theme anthropometric 830:843 arg1 panel 821:825 a panel 819:825 a panel of anthropometric 819:843 FINDINGS The relationships between a panel of anthropometric, metabolic measures and whole blood global protein O-GlcNAc was examined. 25228926 4 52 theme study 407:411 arg1 purpose 391:397 The purpose 387:397 The purpose of this study 387:411 The purpose of this study was to explore the sensitivity of O-GlcNAc expression as a potential marker of early metabolic dysfunction in a young adult population. 25228926 5 53 dep Healthy 549:555 arg1 young 558:562 young 558:562 young 558:562 Healthy, young males (18-35 y) from the Assessing Inherited Metabolic syndrome Markers in the Young study (AIMMY), were divided into low (LH,0.60) or high (HH,1.61) homeostatic model assessment of insulin resistance (HOMA-IR) cohorts. 25228926 5 54 theme Assessing 589:597 arg1 syndrome 619:626 the Assessing Inherited Metabolic syndrome 585:626 the Assessing Inherited Metabolic syndrome Markers in the Young study (AIMMY) 585:661 Healthy, young males (18-35 y) from the Assessing Inherited Metabolic syndrome Markers in the Young study (AIMMY), were divided into low (LH,0.60) or high (HH,1.61) homeostatic model assessment of insulin resistance (HOMA-IR) cohorts. 25228926 9 55 theme O-GlcNAc 1316:1323 arg1 expression 1325:1334 Greater O-GlcNAc expression 1308:1334 Greater O-GlcNAc expression 1308:1334 Greater O-GlcNAc expression was observed in the whole blood of HH compared to LH. 25228926 5 56 theme Metabolic 609:617 arg1 syndrome 619:626 the Assessing Inherited Metabolic syndrome 585:626 the Assessing Inherited Metabolic syndrome Markers in the Young study (AIMMY) 585:661 Healthy, young males (18-35 y) from the Assessing Inherited Metabolic syndrome Markers in the Young study (AIMMY), were divided into low (LH,0.60) or high (HH,1.61) homeostatic model assessment of insulin resistance (HOMA-IR) cohorts. 25228926 13 57 theme healthy 1806:1812 arg1 population 1820:1829 a young healthy adult population 1798:1829 a young healthy adult population free of any clinically relevant pathologies 1798:1873 O-GlcNAc has the potential to serve as a screening tool for predicting future metabolic disturbances in a young healthy adult population free of any clinically relevant pathologies. 25228926 1 58 theme diagnostic 163:172 arg1 tool 174:177 the predominant diagnostic tool 147:177 the predominant diagnostic tool for diabetes diagnosis and progression 147:216 BACKGROUND Hemoglobin A1c (HbA1c) is the predominant diagnostic tool for diabetes diagnosis and progression. 25228926 1 58 theme diagnostic 163:172 arg1 A1c 132:134 BACKGROUND Hemoglobin A1c 110:134 BACKGROUND Hemoglobin A1c (HbA1c) 110:142 BACKGROUND Hemoglobin A1c (HbA1c) is the predominant diagnostic tool for diabetes diagnosis and progression. 25228926 12 59 theme greater 1616:1622 arg1 sensitivity 1624:1634 a greater sensitivity 1614:1634 a greater sensitivity to metabolic status compared to HbA1c 1614:1672 CONCLUSIONS Results indicate that O-GlcNAc has a greater sensitivity to metabolic status compared to HbA1c in this population. 25228926 8 60 theme HOMA-IR 1157:1163 arg1 cohorts 1165:1171 HOMA-IR cohorts 1157:1171 HOMA-IR cohorts 1157:1171 HOMA-IR cohorts showed no differences in BMI, blood glucose or HbA1c, but differed in percent body fat, plasma triglycerides, and circulating insulin. 25228926 9 61 theme whole 1356:1360 arg1 blood 1362:1366 the whole blood 1352:1366 the whole blood of HH compared to LH 1352:1387 Greater O-GlcNAc expression was observed in the whole blood of HH compared to LH. 25228926 6 62 theme protein 888:894 arg1 O-GlcNAc 896:903 whole blood global protein O-GlcNAc 869:903 whole blood global protein O-GlcNAc 869:903 FINDINGS The relationships between a panel of anthropometric, metabolic measures and whole blood global protein O-GlcNAc was examined. 25228926 5 63 dep high 699:702 arg1 HH,1.61 705:711 HH,1.61 705:711 HH,1.61 705:711 Healthy, young males (18-35 y) from the Assessing Inherited Metabolic syndrome Markers in the Young study (AIMMY), were divided into low (LH,0.60) or high (HH,1.61) homeostatic model assessment of insulin resistance (HOMA-IR) cohorts. 25228926 4 64 theme expression 456:465 arg1 marker 482:487 a potential marker 470:487 a potential marker of early metabolic dysfunction 470:518 The purpose of this study was to explore the sensitivity of O-GlcNAc expression as a potential marker of early metabolic dysfunction in a young adult population. 25228926 4 64 theme expression 456:465 arg1 sensitivity 432:442 the sensitivity 428:442 the sensitivity of O-GlcNAc expression 428:465 The purpose of this study was to explore the sensitivity of O-GlcNAc expression as a potential marker of early metabolic dysfunction in a young adult population. 25228926 5 65 theme low 682:684 arg1 assessment 732:741 low (LH,0.60) or high (HH,1.61) homeostatic model assessment 682:741 low (LH,0.60) or high (HH,1.61) homeostatic model assessment of insulin resistance (HOMA-IR) cohorts 682:781 Healthy, young males (18-35 y) from the Assessing Inherited Metabolic syndrome Markers in the Young study (AIMMY), were divided into low (LH,0.60) or high (HH,1.61) homeostatic model assessment of insulin resistance (HOMA-IR) cohorts. 25228926 6 66 theme blood 875:879 arg1 O-GlcNAc 896:903 whole blood global protein O-GlcNAc 869:903 whole blood global protein O-GlcNAc 869:903 FINDINGS The relationships between a panel of anthropometric, metabolic measures and whole blood global protein O-GlcNAc was examined. 25228926 3 67 theme O-linked-β-N-acetylglucosamine 294:323 arg1 modification 336:347 O-linked-β-N-acetylglucosamine (O-GlcNAc) modification 294:347 O-linked-β-N-acetylglucosamine (O-GlcNAc) modification 294:347 O-linked-β-N-acetylglucosamine (O-GlcNAc) modification has emerged as a sensitive biomarker. 25228926 13 68 theme metabolic 1772:1780 arg1 disturbances 1782:1793 future metabolic disturbances 1765:1793 future metabolic disturbances 1765:1793 O-GlcNAc has the potential to serve as a screening tool for predicting future metabolic disturbances in a young healthy adult population free of any clinically relevant pathologies. 25228926 1 69 theme Hemoglobin 121:130 arg1 HbA1c 137:141 HbA1c 137:141 HbA1c 137:141 BACKGROUND Hemoglobin A1c (HbA1c) is the predominant diagnostic tool for diabetes diagnosis and progression. 25228926 1 69 theme Hemoglobin 121:130 arg1 A1c 132:134 BACKGROUND Hemoglobin A1c 110:134 BACKGROUND Hemoglobin A1c (HbA1c) 110:142 BACKGROUND Hemoglobin A1c (HbA1c) is the predominant diagnostic tool for diabetes diagnosis and progression. 25228926 1 69 theme Hemoglobin 121:130 arg1 tool 174:177 the predominant diagnostic tool 147:177 the predominant diagnostic tool for diabetes diagnosis and progression 147:216 BACKGROUND Hemoglobin A1c (HbA1c) is the predominant diagnostic tool for diabetes diagnosis and progression. 25228926 12 70 theme CONCLUSIONS 1567:1577 arg1 Results 1579:1585 CONCLUSIONS Results 1567:1585 CONCLUSIONS Results 1567:1585 CONCLUSIONS Results indicate that O-GlcNAc has a greater sensitivity to metabolic status compared to HbA1c in this population. 25228926 0 71 theme whole 68:72 arg1 blood 74:78 the whole blood 64:78 the whole blood of healthy young adult males 64:107 O-GlcNAc modification is associated with insulin sensitivity in the whole blood of healthy young adult males. 25228926 7 72 theme transferase 941:951 arg1 levels 959:964 O-GlcNAc and O-GlcNAc transferase (OGT) levels 919:964 O-GlcNAc and O-GlcNAc transferase (OGT) levels 919:964 O-GlcNAc and O-GlcNAc transferase (OGT) levels were quantified by immunoblotting and compared to anthropometric measures: body mass index (BMI), percentage body fat, aerobic fitness, blood glucose, triglycerides, HDL, insulin, and HbA1c. 25228926 4 73 theme early 492:496 arg1 dysfunction 508:518 early metabolic dysfunction 492:518 early metabolic dysfunction 492:518 The purpose of this study was to explore the sensitivity of O-GlcNAc expression as a potential marker of early metabolic dysfunction in a young adult population. 25228926 8 74 theme blood 1203:1207 arg1 glucose 1209:1215 blood glucose 1203:1215 blood glucose 1203:1215 HOMA-IR cohorts showed no differences in BMI, blood glucose or HbA1c, but differed in percent body fat, plasma triglycerides, and circulating insulin. 25228926 12 75 contain has 1610:1612 arg1 O-GlcNAc 1601:1608 O-GlcNAc 1601:1608 O-GlcNAc 1601:1608 CONCLUSIONS Results indicate that O-GlcNAc has a greater sensitivity to metabolic status compared to HbA1c in this population. 25228926 12 75 contain has 1610:1612 arg2 sensitivity 1624:1634 a greater sensitivity 1614:1634 a greater sensitivity to metabolic status compared to HbA1c 1614:1672 CONCLUSIONS Results indicate that O-GlcNAc has a greater sensitivity to metabolic status compared to HbA1c in this population. 25228926 3 76 theme O-GlcNAc 326:333 arg1 modification 336:347 O-linked-β-N-acetylglucosamine (O-GlcNAc) modification 294:347 O-linked-β-N-acetylglucosamine (O-GlcNAc) modification 294:347 O-linked-β-N-acetylglucosamine (O-GlcNAc) modification has emerged as a sensitive biomarker. 25228926 4 77 theme dysfunction 508:518 arg1 marker 482:487 a potential marker 470:487 a potential marker of early metabolic dysfunction 470:518 The purpose of this study was to explore the sensitivity of O-GlcNAc expression as a potential marker of early metabolic dysfunction in a young adult population. 25228926 4 77 theme dysfunction 508:518 arg1 sensitivity 432:442 the sensitivity 428:442 the sensitivity of O-GlcNAc expression 428:465 The purpose of this study was to explore the sensitivity of O-GlcNAc expression as a potential marker of early metabolic dysfunction in a young adult population. 25228926 0 78 theme young 91:95 arg1 males 103:107 healthy young adult males 83:107 healthy young adult males 83:107 O-GlcNAc modification is associated with insulin sensitivity in the whole blood of healthy young adult males. 25228926 0 79 theme males 103:107 arg1 blood 74:78 the whole blood 64:78 the whole blood of healthy young adult males 64:107 O-GlcNAc modification is associated with insulin sensitivity in the whole blood of healthy young adult males. 25228926 8 80 from differences 1183:1193 arg1 BMI 1198:1200 BMI 1198:1200 BMI 1198:1200 HOMA-IR cohorts showed no differences in BMI, blood glucose or HbA1c, but differed in percent body fat, plasma triglycerides, and circulating insulin. 25228926 8 80 from differences 1183:1193 arg1 glucose 1209:1215 blood glucose 1203:1215 blood glucose 1203:1215 HOMA-IR cohorts showed no differences in BMI, blood glucose or HbA1c, but differed in percent body fat, plasma triglycerides, and circulating insulin. 25228926 8 80 from differences 1183:1193 arg1 HbA1c 1220:1224 HbA1c 1220:1224 HbA1c 1220:1224 HOMA-IR cohorts showed no differences in BMI, blood glucose or HbA1c, but differed in percent body fat, plasma triglycerides, and circulating insulin. 25228926 7 81 theme blood 1102:1106 arg1 glucose 1108:1114 blood glucose 1102:1114 blood glucose 1102:1114 O-GlcNAc and O-GlcNAc transferase (OGT) levels were quantified by immunoblotting and compared to anthropometric measures: body mass index (BMI), percentage body fat, aerobic fitness, blood glucose, triglycerides, HDL, insulin, and HbA1c. 25228926 8 82 theme percent 1243:1249 arg1 fat 1256:1258 percent body fat 1243:1258 percent body fat 1243:1258 HOMA-IR cohorts showed no differences in BMI, blood glucose or HbA1c, but differed in percent body fat, plasma triglycerides, and circulating insulin. 25228926 5 83 theme resistance 754:763 arg1 cohorts 775:781 insulin resistance (HOMA-IR) cohorts 746:781 insulin resistance (HOMA-IR) cohorts 746:781 Healthy, young males (18-35 y) from the Assessing Inherited Metabolic syndrome Markers in the Young study (AIMMY), were divided into low (LH,0.60) or high (HH,1.61) homeostatic model assessment of insulin resistance (HOMA-IR) cohorts. 25228926 0 84 theme insulin 41:47 arg1 sensitivity 49:59 insulin sensitivity 41:59 insulin sensitivity in the whole blood of healthy young adult males 41:107 O-GlcNAc modification is associated with insulin sensitivity in the whole blood of healthy young adult males. 25228926 5 85 theme cohorts 775:781 arg1 assessment 732:741 low (LH,0.60) or high (HH,1.61) homeostatic model assessment 682:741 low (LH,0.60) or high (HH,1.61) homeostatic model assessment of insulin resistance (HOMA-IR) cohorts 682:781 Healthy, young males (18-35 y) from the Assessing Inherited Metabolic syndrome Markers in the Young study (AIMMY), were divided into low (LH,0.60) or high (HH,1.61) homeostatic model assessment of insulin resistance (HOMA-IR) cohorts. 25228926 8 86 theme plasma 1261:1266 arg1 triglycerides 1268:1280 plasma triglycerides 1261:1280 plasma triglycerides 1261:1280 HOMA-IR cohorts showed no differences in BMI, blood glucose or HbA1c, but differed in percent body fat, plasma triglycerides, and circulating insulin. 25228926 5 87 theme model 726:730 arg1 assessment 732:741 low (LH,0.60) or high (HH,1.61) homeostatic model assessment 682:741 low (LH,0.60) or high (HH,1.61) homeostatic model assessment of insulin resistance (HOMA-IR) cohorts 682:781 Healthy, young males (18-35 y) from the Assessing Inherited Metabolic syndrome Markers in the Young study (AIMMY), were divided into low (LH,0.60) or high (HH,1.61) homeostatic model assessment of insulin resistance (HOMA-IR) cohorts. 25228926 4 88 theme adult 531:535 arg1 population 537:546 a young adult population 523:546 a young adult population 523:546 The purpose of this study was to explore the sensitivity of O-GlcNAc expression as a potential marker of early metabolic dysfunction in a young adult population. 25228926 8 89 theme circulating 1287:1297 arg1 insulin 1299:1305 circulating insulin 1287:1305 circulating insulin 1287:1305 HOMA-IR cohorts showed no differences in BMI, blood glucose or HbA1c, but differed in percent body fat, plasma triglycerides, and circulating insulin. 25228926 13 90 theme relevant 1854:1861 arg1 pathologies 1863:1873 any clinically relevant pathologies 1839:1873 any clinically relevant pathologies 1839:1873 O-GlcNAc has the potential to serve as a screening tool for predicting future metabolic disturbances in a young healthy adult population free of any clinically relevant pathologies. 25018046 4 0 theme O-linked 800:807 arg1 domain 815:820 the O-linked sugar domain 796:820 the O-linked sugar domain 796:820 The longer isoform (TypeI VLDLR) is 3141bp and contains five conserved structural domains, while the other (TypeII VLDLR) lacks 90bp encoding for the O-linked sugar domain. 25018046 10 1 theme developing 1923:1932 arg1 follicles 1934:1942 developing follicles 1923:1942 developing follicles than TypeI VLDLR 1923:1959 Collectively, data from the present study indicate that TypeII VLDLR is more important for the transport of plasma lipoproteins into developing follicles than TypeI VLDLR, and provide new evidence about the influence of steroids in modulating VLDLR gene expression in ovarian cells. 25018046 5 2 from amounts 891:897 arg1 cells 930:934 theca and granulosa cells 910:934 theca and granulosa cells from early stages of follicle development 910:976 TypeII VLDLR was predominantly expressed in the ovary, with greater amounts of mRNA in theca and granulosa cells from early stages of follicle development but decreased during vitellogenesis. 25018046 1 3 theme -mediated 241:249 arg1 endocytosis 251:261 Very low density lipoprotein receptor (VLDLR)-mediated endocytosis 196:261 Very low density lipoprotein receptor (VLDLR)-mediated endocytosis of plasma lipoproteins into the ovary 196:299 Very low density lipoprotein receptor (VLDLR)-mediated endocytosis of plasma lipoproteins into the ovary is essential for ovarian follicle development. 25018046 10 4 theme present 1818:1824 arg1 study 1826:1830 the present study 1814:1830 the present study 1814:1830 Collectively, data from the present study indicate that TypeII VLDLR is more important for the transport of plasma lipoproteins into developing follicles than TypeI VLDLR, and provide new evidence about the influence of steroids in modulating VLDLR gene expression in ovarian cells. 25018046 0 5 from development 157:167 arg1 cygnoide 185:192 Anser cygnoide 179:192 Anser cygnoide 179:192 Molecular cloning, expression profile and transcriptional modulation of two splice variants of very low density lipoprotein receptor during ovarian follicle development in geese (Anser cygnoide). 25018046 0 5 from development 157:167 arg1 geese 172:176 geese 172:176 geese (Anser cygnoide) 172:193 Molecular cloning, expression profile and transcriptional modulation of two splice variants of very low density lipoprotein receptor during ovarian follicle development in geese (Anser cygnoide). 25018046 3 6 theme full-length 527:537 arg1 cDNAs 539:543 the full-length cDNAs 523:543 the full-length cDNAs of two splice isoforms of VLDLR 523:575 In the present study, the full-length cDNAs of two splice isoforms of VLDLR were obtained from geese (Anser cygnoide) ovaries using the RACE method. 25018046 9 7 theme TypeII 1686:1691 arg1 expression 1704:1713 TypeII VLDLR gene expression 1686:1713 TypeII VLDLR gene expression in granulosa cells from both pre-hierarchical and pre-ovulatory follicles 1686:1787 In addition, in vitro experiments suggested that exogenous cholesterol, 25-hydroxycholesterol and mevinolin (a highly potent competitive inhibitor of HMG-CoA) treatment could significantly alter TypeII VLDLR gene expression in granulosa cells from both pre-hierarchical and pre-ovulatory follicles. 25018046 6 8 theme theca 1080:1084 arg1 cells 1086:1090 theca cells 1080:1090 theca cells 1080:1090 However, there was minimal expression of the TypeI VLDLR gene in theca cells and expression was almost undetectable in granulosa cells throughout follicle development. 25018046 9 9 dep mevinolin 1589:1597 arg1 inhibitor 1628:1636 a highly potent competitive inhibitor 1600:1636 a highly potent competitive inhibitor of HMG-CoA 1600:1647 In addition, in vitro experiments suggested that exogenous cholesterol, 25-hydroxycholesterol and mevinolin (a highly potent competitive inhibitor of HMG-CoA) treatment could significantly alter TypeII VLDLR gene expression in granulosa cells from both pre-hierarchical and pre-ovulatory follicles. 25018046 3 10 theme splice 552:557 arg1 isoforms 559:566 two splice isoforms 548:566 two splice isoforms of VLDLR 548:575 In the present study, the full-length cDNAs of two splice isoforms of VLDLR were obtained from geese (Anser cygnoide) ovaries using the RACE method. 25018046 5 11 from stages 947:952 arg1 cells 930:934 theca and granulosa cells 910:934 theca and granulosa cells from early stages of follicle development 910:976 TypeII VLDLR was predominantly expressed in the ovary, with greater amounts of mRNA in theca and granulosa cells from early stages of follicle development but decreased during vitellogenesis. 25018046 5 11 from stages 947:952 arg1 mRNA 902:905 mRNA 902:905 mRNA in theca and granulosa cells from early stages of follicle development 902:976 TypeII VLDLR was predominantly expressed in the ovary, with greater amounts of mRNA in theca and granulosa cells from early stages of follicle development but decreased during vitellogenesis. 25018046 9 12 theme gene 1699:1702 arg1 expression 1704:1713 TypeII VLDLR gene expression 1686:1713 TypeII VLDLR gene expression in granulosa cells from both pre-hierarchical and pre-ovulatory follicles 1686:1787 In addition, in vitro experiments suggested that exogenous cholesterol, 25-hydroxycholesterol and mevinolin (a highly potent competitive inhibitor of HMG-CoA) treatment could significantly alter TypeII VLDLR gene expression in granulosa cells from both pre-hierarchical and pre-ovulatory follicles. 25018046 6 13 theme gene 1072:1075 arg1 expression 1042:1051 minimal expression 1034:1051 minimal expression of the TypeI VLDLR gene in theca cells 1034:1090 However, there was minimal expression of the TypeI VLDLR gene in theca cells and expression was almost undetectable in granulosa cells throughout follicle development. 25018046 10 14 theme new 1974:1976 arg1 evidence 1978:1985 new evidence 1974:1985 new evidence about the influence of steroids in modulating VLDLR gene expression in ovarian cells 1974:2070 Collectively, data from the present study indicate that TypeII VLDLR is more important for the transport of plasma lipoproteins into developing follicles than TypeI VLDLR, and provide new evidence about the influence of steroids in modulating VLDLR gene expression in ovarian cells. 25018046 0 15 theme lipoprotein 112:122 arg1 receptor 124:131 very low density lipoprotein receptor 95:131 very low density lipoprotein receptor 95:131 Molecular cloning, expression profile and transcriptional modulation of two splice variants of very low density lipoprotein receptor during ovarian follicle development in geese (Anser cygnoide). 25018046 8 16 theme yolk 1424:1427 arg1 lipids 1429:1434 yolk lipids 1424:1434 yolk lipids 1424:1434 The significant correlations between transcripts of TypeII VLDLR and yolk lipids supported its important role on yolk lipid deposition. 25018046 10 17 theme steroids 2010:2017 arg1 influence 1997:2005 the influence 1993:2005 the influence of steroids in modulating VLDLR gene expression in ovarian cells 1993:2070 Collectively, data from the present study indicate that TypeII VLDLR is more important for the transport of plasma lipoproteins into developing follicles than TypeI VLDLR, and provide new evidence about the influence of steroids in modulating VLDLR gene expression in ovarian cells. 25018046 1 18 theme density 205:211 arg1 lipoprotein 213:223 Very low density lipoprotein 196:223 Very low density lipoprotein receptor (VLDLR) 196:240 Very low density lipoprotein receptor (VLDLR)-mediated endocytosis of plasma lipoproteins into the ovary is essential for ovarian follicle development. 25018046 7 19 theme size-dependent 1332:1345 arg1 manner 1347:1352 a follicular size-dependent manner 1319:1352 a follicular size-dependent manner 1319:1352 Yolk VLDL concentrations decreased as stage of development advanced while yolk triglyceride and cholesterol concentrations increased in a follicular size-dependent manner. 25018046 4 20 theme TypeI 670:674 arg1 isoform 661:667 The longer isoform 650:667 The longer isoform (TypeI VLDLR) 650:681 The longer isoform (TypeI VLDLR) is 3141bp and contains five conserved structural domains, while the other (TypeII VLDLR) lacks 90bp encoding for the O-linked sugar domain. 25018046 4 20 theme TypeI 670:674 arg1 VLDLR 676:680 TypeI VLDLR 670:680 TypeI VLDLR 670:680 The longer isoform (TypeI VLDLR) is 3141bp and contains five conserved structural domains, while the other (TypeII VLDLR) lacks 90bp encoding for the O-linked sugar domain. 25018046 0 21 theme follicle 148:155 arg1 development 157:167 ovarian follicle development 140:167 ovarian follicle development in geese (Anser cygnoide) 140:193 Molecular cloning, expression profile and transcriptional modulation of two splice variants of very low density lipoprotein receptor during ovarian follicle development in geese (Anser cygnoide). 25018046 5 22 theme follicle 957:964 arg1 development 966:976 follicle development 957:976 follicle development 957:976 TypeII VLDLR was predominantly expressed in the ovary, with greater amounts of mRNA in theca and granulosa cells from early stages of follicle development but decreased during vitellogenesis. 25018046 8 23 theme important 1450:1458 arg1 role 1460:1463 its important role 1446:1463 its important role 1446:1463 The significant correlations between transcripts of TypeII VLDLR and yolk lipids supported its important role on yolk lipid deposition. 25018046 6 24 theme granulosa 1134:1142 arg1 cells 1144:1148 granulosa cells 1134:1148 granulosa cells 1134:1148 However, there was minimal expression of the TypeI VLDLR gene in theca cells and expression was almost undetectable in granulosa cells throughout follicle development. 25018046 6 25 from cells 1144:1148 arg1 undetectable 1118:1129 undetectable 1118:1129 undetectable 1118:1129 However, there was minimal expression of the TypeI VLDLR gene in theca cells and expression was almost undetectable in granulosa cells throughout follicle development. 25018046 10 26 theme gene 2039:2042 arg1 expression 2044:2053 VLDLR gene expression 2033:2053 VLDLR gene expression in ovarian cells 2033:2070 Collectively, data from the present study indicate that TypeII VLDLR is more important for the transport of plasma lipoproteins into developing follicles than TypeI VLDLR, and provide new evidence about the influence of steroids in modulating VLDLR gene expression in ovarian cells. 25018046 9 27 theme pre-ovulatory 1765:1777 arg1 follicles 1779:1787 both pre-hierarchical and pre-ovulatory follicles 1739:1787 follicles 1779:1787 In addition, in vitro experiments suggested that exogenous cholesterol, 25-hydroxycholesterol and mevinolin (a highly potent competitive inhibitor of HMG-CoA) treatment could significantly alter TypeII VLDLR gene expression in granulosa cells from both pre-hierarchical and pre-ovulatory follicles. 25018046 1 28 theme ovarian 318:324 arg1 development 335:345 ovarian follicle development 318:345 ovarian follicle development 318:345 Very low density lipoprotein receptor (VLDLR)-mediated endocytosis of plasma lipoproteins into the ovary is essential for ovarian follicle development. 25018046 5 29 theme TypeII 823:828 arg1 VLDLR 830:834 TypeII VLDLR 823:834 TypeII VLDLR 823:834 TypeII VLDLR was predominantly expressed in the ovary, with greater amounts of mRNA in theca and granulosa cells from early stages of follicle development but decreased during vitellogenesis. 25018046 2 30 theme ovarian 471:477 arg1 follicles 490:498 ovarian developing follicles 471:498 ovarian developing follicles 471:498 Two splice variants of VLDLR have been identified in several species, yet little is known about their distinctive roles in ovarian developing follicles. 25018046 8 31 theme lipid 1473:1477 arg1 deposition 1479:1488 yolk lipid deposition 1468:1488 yolk lipid deposition 1468:1488 The significant correlations between transcripts of TypeII VLDLR and yolk lipids supported its important role on yolk lipid deposition. 25018046 0 32 theme splice 76:81 arg1 variants 83:90 two splice variants 72:90 two splice variants of very low density lipoprotein receptor 72:131 Molecular cloning, expression profile and transcriptional modulation of two splice variants of very low density lipoprotein receptor during ovarian follicle development in geese (Anser cygnoide). 25018046 4 33 theme conserved 711:719 arg1 domains 732:738 five conserved structural domains 706:738 five conserved structural domains 706:738 The longer isoform (TypeI VLDLR) is 3141bp and contains five conserved structural domains, while the other (TypeII VLDLR) lacks 90bp encoding for the O-linked sugar domain. 25018046 9 34 from expression 1704:1713 arg1 follicles 1779:1787 both pre-hierarchical and pre-ovulatory follicles 1739:1787 follicles 1779:1787 In addition, in vitro experiments suggested that exogenous cholesterol, 25-hydroxycholesterol and mevinolin (a highly potent competitive inhibitor of HMG-CoA) treatment could significantly alter TypeII VLDLR gene expression in granulosa cells from both pre-hierarchical and pre-ovulatory follicles. 25018046 9 34 from expression 1704:1713 arg1 cells 1728:1732 granulosa cells 1718:1732 granulosa cells from both pre-hierarchical and pre-ovulatory follicles 1718:1787 In addition, in vitro experiments suggested that exogenous cholesterol, 25-hydroxycholesterol and mevinolin (a highly potent competitive inhibitor of HMG-CoA) treatment could significantly alter TypeII VLDLR gene expression in granulosa cells from both pre-hierarchical and pre-ovulatory follicles. 25018046 0 35 theme low 100:102 arg1 lipoprotein 112:122 very low density lipoprotein 95:122 very low density lipoprotein receptor 95:131 Molecular cloning, expression profile and transcriptional modulation of two splice variants of very low density lipoprotein receptor during ovarian follicle development in geese (Anser cygnoide). 25018046 9 36 theme exogenous 1540:1548 arg1 treatment 1650:1658 exogenous cholesterol, 25-hydroxycholesterol and mevinolin (a highly potent competitive inhibitor of HMG-CoA) treatment 1540:1658 exogenous cholesterol, 25-hydroxycholesterol and mevinolin (a highly potent competitive inhibitor of HMG-CoA) treatment 1540:1658 In addition, in vitro experiments suggested that exogenous cholesterol, 25-hydroxycholesterol and mevinolin (a highly potent competitive inhibitor of HMG-CoA) treatment could significantly alter TypeII VLDLR gene expression in granulosa cells from both pre-hierarchical and pre-ovulatory follicles. 25018046 9 37 dep in 1504:1505 arg1 vitro 1507:1511 vitro 1507:1511 vitro 1507:1511 In addition, in vitro experiments suggested that exogenous cholesterol, 25-hydroxycholesterol and mevinolin (a highly potent competitive inhibitor of HMG-CoA) treatment could significantly alter TypeII VLDLR gene expression in granulosa cells from both pre-hierarchical and pre-ovulatory follicles. 25018046 0 38 theme Molecular 0:8 arg1 cloning 10:16 Molecular cloning 0:16 Molecular cloning 0:16 Molecular cloning, expression profile and transcriptional modulation of two splice variants of very low density lipoprotein receptor during ovarian follicle development in geese (Anser cygnoide). 25018046 1 39 theme plasma 266:271 arg1 lipoproteins 273:284 plasma lipoproteins 266:284 plasma lipoproteins 266:284 Very low density lipoprotein receptor (VLDLR)-mediated endocytosis of plasma lipoproteins into the ovary is essential for ovarian follicle development. 25018046 5 40 theme greater 883:889 arg1 mRNA 902:905 mRNA 902:905 mRNA in theca and granulosa cells from early stages of follicle development 902:976 TypeII VLDLR was predominantly expressed in the ovary, with greater amounts of mRNA in theca and granulosa cells from early stages of follicle development but decreased during vitellogenesis. 25018046 5 40 theme greater 883:889 arg1 amounts 891:897 greater amounts 883:897 greater amounts of mRNA in theca and granulosa cells from early stages of follicle development 883:976 TypeII VLDLR was predominantly expressed in the ovary, with greater amounts of mRNA in theca and granulosa cells from early stages of follicle development but decreased during vitellogenesis. 25018046 7 41 theme yolk 1257:1260 arg1 triglyceride 1262:1273 yolk triglyceride and cholesterol concentrations 1257:1304 triglyceride 1262:1273 Yolk VLDL concentrations decreased as stage of development advanced while yolk triglyceride and cholesterol concentrations increased in a follicular size-dependent manner. 25018046 4 42 theme TypeII 758:763 arg1 other 751:755 other 751:755 other 751:755 The longer isoform (TypeI VLDLR) is 3141bp and contains five conserved structural domains, while the other (TypeII VLDLR) lacks 90bp encoding for the O-linked sugar domain. 25018046 4 42 theme TypeII 758:763 arg1 VLDLR 765:769 TypeII VLDLR 758:769 TypeII VLDLR 758:769 The longer isoform (TypeI VLDLR) is 3141bp and contains five conserved structural domains, while the other (TypeII VLDLR) lacks 90bp encoding for the O-linked sugar domain. 25018046 2 43 theme several 401:407 arg1 species 409:415 several species 401:415 several species 401:415 Two splice variants of VLDLR have been identified in several species, yet little is known about their distinctive roles in ovarian developing follicles. 25018046 5 44 theme early 941:945 arg1 stages 947:952 early stages 941:952 early stages of follicle development 941:976 TypeII VLDLR was predominantly expressed in the ovary, with greater amounts of mRNA in theca and granulosa cells from early stages of follicle development but decreased during vitellogenesis. 25018046 7 45 theme advanced 1242:1249 arg1 development 1230:1240 development advanced 1230:1249 development advanced 1230:1249 Yolk VLDL concentrations decreased as stage of development advanced while yolk triglyceride and cholesterol concentrations increased in a follicular size-dependent manner. 25018046 3 46 theme cygnoide 609:616 arg1 ovaries 619:625 geese (Anser cygnoide) ovaries 596:625 geese (Anser cygnoide) ovaries using the RACE method 596:647 In the present study, the full-length cDNAs of two splice isoforms of VLDLR were obtained from geese (Anser cygnoide) ovaries using the RACE method. 25018046 6 47 from expression 1042:1051 arg1 cells 1086:1090 theca cells 1080:1090 theca cells 1080:1090 However, there was minimal expression of the TypeI VLDLR gene in theca cells and expression was almost undetectable in granulosa cells throughout follicle development. 25018046 0 48 theme transcriptional 42:56 arg1 modulation 58:67 transcriptional modulation 42:67 transcriptional modulation of two splice variants of very low density lipoprotein receptor during ovarian follicle development in geese (Anser cygnoide) 42:193 Molecular cloning, expression profile and transcriptional modulation of two splice variants of very low density lipoprotein receptor during ovarian follicle development in geese (Anser cygnoide). 25018046 10 49 from expression 2044:2053 arg1 cells 2066:2070 ovarian cells 2058:2070 ovarian cells 2058:2070 Collectively, data from the present study indicate that TypeII VLDLR is more important for the transport of plasma lipoproteins into developing follicles than TypeI VLDLR, and provide new evidence about the influence of steroids in modulating VLDLR gene expression in ovarian cells. 25018046 9 50 from follicles 1779:1787 arg1 expression 1704:1713 TypeII VLDLR gene expression 1686:1713 TypeII VLDLR gene expression in granulosa cells from both pre-hierarchical and pre-ovulatory follicles 1686:1787 In addition, in vitro experiments suggested that exogenous cholesterol, 25-hydroxycholesterol and mevinolin (a highly potent competitive inhibitor of HMG-CoA) treatment could significantly alter TypeII VLDLR gene expression in granulosa cells from both pre-hierarchical and pre-ovulatory follicles. 25018046 9 50 from follicles 1779:1787 arg1 cells 1728:1732 granulosa cells 1718:1732 granulosa cells from both pre-hierarchical and pre-ovulatory follicles 1718:1787 In addition, in vitro experiments suggested that exogenous cholesterol, 25-hydroxycholesterol and mevinolin (a highly potent competitive inhibitor of HMG-CoA) treatment could significantly alter TypeII VLDLR gene expression in granulosa cells from both pre-hierarchical and pre-ovulatory follicles. 25018046 10 51 theme plasma 1898:1903 arg1 lipoproteins 1905:1916 plasma lipoproteins 1898:1916 plasma lipoproteins 1898:1916 Collectively, data from the present study indicate that TypeII VLDLR is more important for the transport of plasma lipoproteins into developing follicles than TypeI VLDLR, and provide new evidence about the influence of steroids in modulating VLDLR gene expression in ovarian cells. 25018046 8 52 theme TypeII 1407:1412 arg1 VLDLR 1414:1418 TypeII VLDLR 1407:1418 TypeII VLDLR 1407:1418 The significant correlations between transcripts of TypeII VLDLR and yolk lipids supported its important role on yolk lipid deposition. 25018046 1 53 theme lipoprotein 213:223 arg1 VLDLR 235:239 VLDLR 235:239 VLDLR 235:239 Very low density lipoprotein receptor (VLDLR)-mediated endocytosis of plasma lipoproteins into the ovary is essential for ovarian follicle development. 25018046 1 53 theme lipoprotein 213:223 arg1 receptor 225:232 Very low density lipoprotein receptor 196:232 Very low density lipoprotein receptor (VLDLR) 196:240 Very low density lipoprotein receptor (VLDLR)-mediated endocytosis of plasma lipoproteins into the ovary is essential for ovarian follicle development. 25018046 9 54 theme competitive 1616:1626 arg1 inhibitor 1628:1636 a highly potent competitive inhibitor 1600:1636 a highly potent competitive inhibitor of HMG-CoA 1600:1647 In addition, in vitro experiments suggested that exogenous cholesterol, 25-hydroxycholesterol and mevinolin (a highly potent competitive inhibitor of HMG-CoA) treatment could significantly alter TypeII VLDLR gene expression in granulosa cells from both pre-hierarchical and pre-ovulatory follicles. 25018046 0 55 theme Anser 179:183 arg1 cygnoide 185:192 Anser cygnoide 179:192 Anser cygnoide 179:192 Molecular cloning, expression profile and transcriptional modulation of two splice variants of very low density lipoprotein receptor during ovarian follicle development in geese (Anser cygnoide). 25018046 0 55 theme Anser 179:183 arg1 geese 172:176 geese 172:176 geese (Anser cygnoide) 172:193 Molecular cloning, expression profile and transcriptional modulation of two splice variants of very low density lipoprotein receptor during ovarian follicle development in geese (Anser cygnoide). 25018046 2 56 theme splice 352:357 arg1 variants 359:366 Two splice variants 348:366 Two splice variants of VLDLR 348:375 Two splice variants of VLDLR have been identified in several species, yet little is known about their distinctive roles in ovarian developing follicles. 25018046 7 57 theme Yolk 1183:1186 arg1 concentrations 1193:1206 Yolk VLDL concentrations 1183:1206 Yolk VLDL concentrations 1183:1206 Yolk VLDL concentrations decreased as stage of development advanced while yolk triglyceride and cholesterol concentrations increased in a follicular size-dependent manner. 25018046 9 58 theme HMG-CoA 1641:1647 arg1 inhibitor 1628:1636 a highly potent competitive inhibitor 1600:1636 a highly potent competitive inhibitor of HMG-CoA 1600:1647 In addition, in vitro experiments suggested that exogenous cholesterol, 25-hydroxycholesterol and mevinolin (a highly potent competitive inhibitor of HMG-CoA) treatment could significantly alter TypeII VLDLR gene expression in granulosa cells from both pre-hierarchical and pre-ovulatory follicles. 25018046 4 59 theme sugar 809:813 arg1 domain 815:820 the O-linked sugar domain 796:820 the O-linked sugar domain 796:820 The longer isoform (TypeI VLDLR) is 3141bp and contains five conserved structural domains, while the other (TypeII VLDLR) lacks 90bp encoding for the O-linked sugar domain. 25018046 9 60 theme potent 1609:1614 arg1 inhibitor 1628:1636 a highly potent competitive inhibitor 1600:1636 a highly potent competitive inhibitor of HMG-CoA 1600:1647 In addition, in vitro experiments suggested that exogenous cholesterol, 25-hydroxycholesterol and mevinolin (a highly potent competitive inhibitor of HMG-CoA) treatment could significantly alter TypeII VLDLR gene expression in granulosa cells from both pre-hierarchical and pre-ovulatory follicles. 25018046 5 61 from cells 930:934 arg1 mRNA 902:905 mRNA 902:905 mRNA in theca and granulosa cells from early stages of follicle development 902:976 TypeII VLDLR was predominantly expressed in the ovary, with greater amounts of mRNA in theca and granulosa cells from early stages of follicle development but decreased during vitellogenesis. 25018046 5 61 from cells 930:934 arg1 amounts 891:897 greater amounts 883:897 greater amounts of mRNA in theca and granulosa cells from early stages of follicle development 883:976 TypeII VLDLR was predominantly expressed in the ovary, with greater amounts of mRNA in theca and granulosa cells from early stages of follicle development but decreased during vitellogenesis. 25018046 10 62 theme TypeI 1949:1953 arg1 VLDLR 1955:1959 TypeI VLDLR 1949:1959 TypeI VLDLR 1949:1959 Collectively, data from the present study indicate that TypeII VLDLR is more important for the transport of plasma lipoproteins into developing follicles than TypeI VLDLR, and provide new evidence about the influence of steroids in modulating VLDLR gene expression in ovarian cells. 25018046 9 63 theme VLDLR 1693:1697 arg1 expression 1704:1713 TypeII VLDLR gene expression 1686:1713 TypeII VLDLR gene expression in granulosa cells from both pre-hierarchical and pre-ovulatory follicles 1686:1787 In addition, in vitro experiments suggested that exogenous cholesterol, 25-hydroxycholesterol and mevinolin (a highly potent competitive inhibitor of HMG-CoA) treatment could significantly alter TypeII VLDLR gene expression in granulosa cells from both pre-hierarchical and pre-ovulatory follicles. 25018046 10 64 theme lipoproteins 1905:1916 arg1 transport 1885:1893 the transport 1881:1893 the transport of plasma lipoproteins into developing follicles than TypeI VLDLR 1881:1959 Collectively, data from the present study indicate that TypeII VLDLR is more important for the transport of plasma lipoproteins into developing follicles than TypeI VLDLR, and provide new evidence about the influence of steroids in modulating VLDLR gene expression in ovarian cells. 25018046 4 65 link O-linked 800:807 arg1 domain 815:820 the O-linked sugar domain 796:820 the O-linked sugar domain 796:820 The longer isoform (TypeI VLDLR) is 3141bp and contains five conserved structural domains, while the other (TypeII VLDLR) lacks 90bp encoding for the O-linked sugar domain. 25018046 4 66 contain contains 697:704 arg2 domains 732:738 five conserved structural domains 706:738 five conserved structural domains 706:738 The longer isoform (TypeI VLDLR) is 3141bp and contains five conserved structural domains, while the other (TypeII VLDLR) lacks 90bp encoding for the O-linked sugar domain. 25018046 4 66 contain contains 697:704 arg1 isoform 661:667 The longer isoform 650:667 The longer isoform (TypeI VLDLR) 650:681 The longer isoform (TypeI VLDLR) is 3141bp and contains five conserved structural domains, while the other (TypeII VLDLR) lacks 90bp encoding for the O-linked sugar domain. 25018046 4 66 contain contains 697:704 arg1 VLDLR 676:680 TypeI VLDLR 670:680 TypeI VLDLR 670:680 The longer isoform (TypeI VLDLR) is 3141bp and contains five conserved structural domains, while the other (TypeII VLDLR) lacks 90bp encoding for the O-linked sugar domain. 25018046 4 66 contain contains 697:704 arg1 while 741:745 while 741:745 while 741:745 The longer isoform (TypeI VLDLR) is 3141bp and contains five conserved structural domains, while the other (TypeII VLDLR) lacks 90bp encoding for the O-linked sugar domain. 25018046 4 66 contain contains 697:704 arg1 3141bp 686:691 3141bp 686:691 3141bp 686:691 The longer isoform (TypeI VLDLR) is 3141bp and contains five conserved structural domains, while the other (TypeII VLDLR) lacks 90bp encoding for the O-linked sugar domain. 25018046 0 67 theme receptor 124:131 arg1 variants 83:90 two splice variants 72:90 two splice variants of very low density lipoprotein receptor 72:131 Molecular cloning, expression profile and transcriptional modulation of two splice variants of very low density lipoprotein receptor during ovarian follicle development in geese (Anser cygnoide). 25018046 8 68 theme lipids 1429:1434 arg1 transcripts 1392:1402 transcripts 1392:1402 transcripts of TypeII VLDLR and yolk lipids 1392:1434 The significant correlations between transcripts of TypeII VLDLR and yolk lipids supported its important role on yolk lipid deposition. 25018046 6 69 theme VLDLR 1066:1070 arg1 gene 1072:1075 the TypeI VLDLR gene 1056:1075 the TypeI VLDLR gene 1056:1075 However, there was minimal expression of the TypeI VLDLR gene in theca cells and expression was almost undetectable in granulosa cells throughout follicle development. 25018046 0 70 theme ovarian 140:146 arg1 development 157:167 ovarian follicle development 140:167 ovarian follicle development in geese (Anser cygnoide) 140:193 Molecular cloning, expression profile and transcriptional modulation of two splice variants of very low density lipoprotein receptor during ovarian follicle development in geese (Anser cygnoide). 25018046 3 71 theme VLDLR 571:575 arg1 isoforms 559:566 two splice isoforms 548:566 two splice isoforms of VLDLR 548:575 In the present study, the full-length cDNAs of two splice isoforms of VLDLR were obtained from geese (Anser cygnoide) ovaries using the RACE method. 25018046 1 72 theme low 201:203 arg1 lipoprotein 213:223 Very low density lipoprotein 196:223 Very low density lipoprotein receptor (VLDLR) 196:240 Very low density lipoprotein receptor (VLDLR)-mediated endocytosis of plasma lipoproteins into the ovary is essential for ovarian follicle development. 25018046 9 73 theme granulosa 1718:1726 arg1 cells 1728:1732 granulosa cells 1718:1732 granulosa cells from both pre-hierarchical and pre-ovulatory follicles 1718:1787 In addition, in vitro experiments suggested that exogenous cholesterol, 25-hydroxycholesterol and mevinolin (a highly potent competitive inhibitor of HMG-CoA) treatment could significantly alter TypeII VLDLR gene expression in granulosa cells from both pre-hierarchical and pre-ovulatory follicles. 25018046 6 74 theme follicle 1161:1168 arg1 development 1170:1180 follicle development 1161:1180 follicle development 1161:1180 However, there was minimal expression of the TypeI VLDLR gene in theca cells and expression was almost undetectable in granulosa cells throughout follicle development. 25018046 3 75 theme isoforms 559:566 arg1 cDNAs 539:543 the full-length cDNAs 523:543 the full-length cDNAs of two splice isoforms of VLDLR 523:575 In the present study, the full-length cDNAs of two splice isoforms of VLDLR were obtained from geese (Anser cygnoide) ovaries using the RACE method. 25018046 5 76 theme development 966:976 arg1 stages 947:952 early stages 941:952 early stages of follicle development 941:976 TypeII VLDLR was predominantly expressed in the ovary, with greater amounts of mRNA in theca and granulosa cells from early stages of follicle development but decreased during vitellogenesis. 25018046 3 77 theme geese 596:600 arg1 ovaries 619:625 geese (Anser cygnoide) ovaries 596:625 geese (Anser cygnoide) ovaries using the RACE method 596:647 In the present study, the full-length cDNAs of two splice isoforms of VLDLR were obtained from geese (Anser cygnoide) ovaries using the RACE method. 25018046 4 78 dep 3141bp 686:691 arg1 isoform 661:667 The longer isoform 650:667 The longer isoform (TypeI VLDLR) 650:681 The longer isoform (TypeI VLDLR) is 3141bp and contains five conserved structural domains, while the other (TypeII VLDLR) lacks 90bp encoding for the O-linked sugar domain. 25018046 4 78 dep 3141bp 686:691 arg1 while 741:745 while 741:745 while 741:745 The longer isoform (TypeI VLDLR) is 3141bp and contains five conserved structural domains, while the other (TypeII VLDLR) lacks 90bp encoding for the O-linked sugar domain. 25018046 4 78 dep 3141bp 686:691 arg1 3141bp 686:691 3141bp 686:691 3141bp 686:691 The longer isoform (TypeI VLDLR) is 3141bp and contains five conserved structural domains, while the other (TypeII VLDLR) lacks 90bp encoding for the O-linked sugar domain. 25018046 9 79 theme pre-hierarchical 1744:1759 arg1 follicles 1779:1787 both pre-hierarchical and pre-ovulatory follicles 1739:1787 follicles 1779:1787 In addition, in vitro experiments suggested that exogenous cholesterol, 25-hydroxycholesterol and mevinolin (a highly potent competitive inhibitor of HMG-CoA) treatment could significantly alter TypeII VLDLR gene expression in granulosa cells from both pre-hierarchical and pre-ovulatory follicles. 25018046 8 80 theme yolk 1468:1471 arg1 deposition 1479:1488 yolk lipid deposition 1468:1488 yolk lipid deposition 1468:1488 The significant correlations between transcripts of TypeII VLDLR and yolk lipids supported its important role on yolk lipid deposition. 25018046 7 81 theme follicular 1321:1330 arg1 manner 1347:1352 a follicular size-dependent manner 1319:1352 a follicular size-dependent manner 1319:1352 Yolk VLDL concentrations decreased as stage of development advanced while yolk triglyceride and cholesterol concentrations increased in a follicular size-dependent manner. 25018046 10 82 theme VLDLR 2033:2037 arg1 expression 2044:2053 VLDLR gene expression 2033:2053 VLDLR gene expression in ovarian cells 2033:2070 Collectively, data from the present study indicate that TypeII VLDLR is more important for the transport of plasma lipoproteins into developing follicles than TypeI VLDLR, and provide new evidence about the influence of steroids in modulating VLDLR gene expression in ovarian cells. 25018046 10 83 theme TypeII 1846:1851 arg1 VLDLR 1853:1857 TypeII VLDLR 1846:1857 TypeII VLDLR 1846:1857 Collectively, data from the present study indicate that TypeII VLDLR is more important for the transport of plasma lipoproteins into developing follicles than TypeI VLDLR, and provide new evidence about the influence of steroids in modulating VLDLR gene expression in ovarian cells. 25018046 2 84 theme developing 479:488 arg1 follicles 490:498 ovarian developing follicles 471:498 ovarian developing follicles 471:498 Two splice variants of VLDLR have been identified in several species, yet little is known about their distinctive roles in ovarian developing follicles. 25018046 6 85 from undetectable 1118:1129 arg1 cells 1144:1148 granulosa cells 1134:1148 granulosa cells 1134:1148 However, there was minimal expression of the TypeI VLDLR gene in theca cells and expression was almost undetectable in granulosa cells throughout follicle development. 25018046 0 86 theme variants 83:90 arg1 cloning 10:16 Molecular cloning 0:16 Molecular cloning 0:16 Molecular cloning, expression profile and transcriptional modulation of two splice variants of very low density lipoprotein receptor during ovarian follicle development in geese (Anser cygnoide). 25018046 0 86 theme variants 83:90 arg1 profile 30:36 expression profile 19:36 expression profile 19:36 Molecular cloning, expression profile and transcriptional modulation of two splice variants of very low density lipoprotein receptor during ovarian follicle development in geese (Anser cygnoide). 25018046 0 86 theme variants 83:90 arg1 modulation 58:67 transcriptional modulation 42:67 transcriptional modulation of two splice variants of very low density lipoprotein receptor during ovarian follicle development in geese (Anser cygnoide) 42:193 Molecular cloning, expression profile and transcriptional modulation of two splice variants of very low density lipoprotein receptor during ovarian follicle development in geese (Anser cygnoide). 25018046 1 87 theme follicle 326:333 arg1 development 335:345 ovarian follicle development 318:345 ovarian follicle development 318:345 Very low density lipoprotein receptor (VLDLR)-mediated endocytosis of plasma lipoproteins into the ovary is essential for ovarian follicle development. 25018046 9 88 theme in 1504:1505 arg1 experiments 1513:1523 in vitro experiments 1504:1523 in vitro experiments 1504:1523 In addition, in vitro experiments suggested that exogenous cholesterol, 25-hydroxycholesterol and mevinolin (a highly potent competitive inhibitor of HMG-CoA) treatment could significantly alter TypeII VLDLR gene expression in granulosa cells from both pre-hierarchical and pre-ovulatory follicles. 25018046 4 89 theme longer 654:659 arg1 isoform 661:667 The longer isoform 650:667 The longer isoform (TypeI VLDLR) 650:681 The longer isoform (TypeI VLDLR) is 3141bp and contains five conserved structural domains, while the other (TypeII VLDLR) lacks 90bp encoding for the O-linked sugar domain. 25018046 4 89 theme longer 654:659 arg1 VLDLR 676:680 TypeI VLDLR 670:680 TypeI VLDLR 670:680 The longer isoform (TypeI VLDLR) is 3141bp and contains five conserved structural domains, while the other (TypeII VLDLR) lacks 90bp encoding for the O-linked sugar domain. 25018046 4 89 theme longer 654:659 arg1 while 741:745 while 741:745 while 741:745 The longer isoform (TypeI VLDLR) is 3141bp and contains five conserved structural domains, while the other (TypeII VLDLR) lacks 90bp encoding for the O-linked sugar domain. 25018046 4 89 theme longer 654:659 arg1 3141bp 686:691 3141bp 686:691 3141bp 686:691 The longer isoform (TypeI VLDLR) is 3141bp and contains five conserved structural domains, while the other (TypeII VLDLR) lacks 90bp encoding for the O-linked sugar domain. 25018046 10 90 theme ovarian 2058:2064 arg1 cells 2066:2070 ovarian cells 2058:2070 ovarian cells 2058:2070 Collectively, data from the present study indicate that TypeII VLDLR is more important for the transport of plasma lipoproteins into developing follicles than TypeI VLDLR, and provide new evidence about the influence of steroids in modulating VLDLR gene expression in ovarian cells. 25018046 0 91 theme density 104:110 arg1 lipoprotein 112:122 very low density lipoprotein 95:122 very low density lipoprotein receptor 95:131 Molecular cloning, expression profile and transcriptional modulation of two splice variants of very low density lipoprotein receptor during ovarian follicle development in geese (Anser cygnoide). 25018046 5 92 theme mRNA 902:905 arg1 mRNA 902:905 mRNA 902:905 mRNA in theca and granulosa cells from early stages of follicle development 902:976 TypeII VLDLR was predominantly expressed in the ovary, with greater amounts of mRNA in theca and granulosa cells from early stages of follicle development but decreased during vitellogenesis. 25018046 5 92 theme mRNA 902:905 arg1 amounts 891:897 greater amounts 883:897 greater amounts of mRNA in theca and granulosa cells from early stages of follicle development 883:976 TypeII VLDLR was predominantly expressed in the ovary, with greater amounts of mRNA in theca and granulosa cells from early stages of follicle development but decreased during vitellogenesis. 25018046 7 93 theme cholesterol 1279:1289 arg1 concentrations 1291:1304 yolk triglyceride and cholesterol concentrations 1257:1304 concentrations 1291:1304 Yolk VLDL concentrations decreased as stage of development advanced while yolk triglyceride and cholesterol concentrations increased in a follicular size-dependent manner. 25018046 2 94 from roles 462:466 arg1 follicles 490:498 ovarian developing follicles 471:498 ovarian developing follicles 471:498 Two splice variants of VLDLR have been identified in several species, yet little is known about their distinctive roles in ovarian developing follicles. 25018046 4 95 theme structural 721:730 arg1 domains 732:738 five conserved structural domains 706:738 five conserved structural domains 706:738 The longer isoform (TypeI VLDLR) is 3141bp and contains five conserved structural domains, while the other (TypeII VLDLR) lacks 90bp encoding for the O-linked sugar domain. 25018046 9 96 theme cholesterol 1550:1560 arg1 treatment 1650:1658 exogenous cholesterol, 25-hydroxycholesterol and mevinolin (a highly potent competitive inhibitor of HMG-CoA) treatment 1540:1658 exogenous cholesterol, 25-hydroxycholesterol and mevinolin (a highly potent competitive inhibitor of HMG-CoA) treatment 1540:1658 In addition, in vitro experiments suggested that exogenous cholesterol, 25-hydroxycholesterol and mevinolin (a highly potent competitive inhibitor of HMG-CoA) treatment could significantly alter TypeII VLDLR gene expression in granulosa cells from both pre-hierarchical and pre-ovulatory follicles. 25018046 10 97 from study 1826:1830 arg1 data 1804:1807 data 1804:1807 data from the present study 1804:1830 Collectively, data from the present study indicate that TypeII VLDLR is more important for the transport of plasma lipoproteins into developing follicles than TypeI VLDLR, and provide new evidence about the influence of steroids in modulating VLDLR gene expression in ovarian cells. 25018046 2 98 theme VLDLR 371:375 arg1 variants 359:366 Two splice variants 348:366 Two splice variants of VLDLR 348:375 Two splice variants of VLDLR have been identified in several species, yet little is known about their distinctive roles in ovarian developing follicles. 25018046 0 99 theme expression 19:28 arg1 profile 30:36 expression profile 19:36 expression profile 19:36 Molecular cloning, expression profile and transcriptional modulation of two splice variants of very low density lipoprotein receptor during ovarian follicle development in geese (Anser cygnoide). 25018046 1 100 theme lipoproteins 273:284 arg1 endocytosis 251:261 Very low density lipoprotein receptor (VLDLR)-mediated endocytosis 196:261 Very low density lipoprotein receptor (VLDLR)-mediated endocytosis of plasma lipoproteins into the ovary 196:299 Very low density lipoprotein receptor (VLDLR)-mediated endocytosis of plasma lipoproteins into the ovary is essential for ovarian follicle development. 25018046 9 101 theme 25-hydroxycholesterol 1563:1583 arg1 treatment 1650:1658 exogenous cholesterol, 25-hydroxycholesterol and mevinolin (a highly potent competitive inhibitor of HMG-CoA) treatment 1540:1658 exogenous cholesterol, 25-hydroxycholesterol and mevinolin (a highly potent competitive inhibitor of HMG-CoA) treatment 1540:1658 In addition, in vitro experiments suggested that exogenous cholesterol, 25-hydroxycholesterol and mevinolin (a highly potent competitive inhibitor of HMG-CoA) treatment could significantly alter TypeII VLDLR gene expression in granulosa cells from both pre-hierarchical and pre-ovulatory follicles. 25018046 6 102 theme minimal 1034:1040 arg1 expression 1042:1051 minimal expression 1034:1051 minimal expression of the TypeI VLDLR gene in theca cells 1034:1090 However, there was minimal expression of the TypeI VLDLR gene in theca cells and expression was almost undetectable in granulosa cells throughout follicle development. 25018046 9 103 theme mevinolin 1589:1597 arg1 treatment 1650:1658 exogenous cholesterol, 25-hydroxycholesterol and mevinolin (a highly potent competitive inhibitor of HMG-CoA) treatment 1540:1658 exogenous cholesterol, 25-hydroxycholesterol and mevinolin (a highly potent competitive inhibitor of HMG-CoA) treatment 1540:1658 In addition, in vitro experiments suggested that exogenous cholesterol, 25-hydroxycholesterol and mevinolin (a highly potent competitive inhibitor of HMG-CoA) treatment could significantly alter TypeII VLDLR gene expression in granulosa cells from both pre-hierarchical and pre-ovulatory follicles. 25018046 7 104 theme development 1230:1240 arg1 stage 1221:1225 stage 1221:1225 stage of development advanced 1221:1249 Yolk VLDL concentrations decreased as stage of development advanced while yolk triglyceride and cholesterol concentrations increased in a follicular size-dependent manner. 25018046 2 105 theme distinctive 450:460 arg1 roles 462:466 their distinctive roles 444:466 their distinctive roles in ovarian developing follicles 444:498 Two splice variants of VLDLR have been identified in several species, yet little is known about their distinctive roles in ovarian developing follicles. 25018046 3 106 theme Anser 603:607 arg1 ovaries 619:625 geese (Anser cygnoide) ovaries 596:625 geese (Anser cygnoide) ovaries using the RACE method 596:647 In the present study, the full-length cDNAs of two splice isoforms of VLDLR were obtained from geese (Anser cygnoide) ovaries using the RACE method. 25018046 8 107 theme significant 1359:1369 arg1 correlations 1371:1382 The significant correlations 1355:1382 The significant correlations between transcripts of TypeII VLDLR and yolk lipids 1355:1434 The significant correlations between transcripts of TypeII VLDLR and yolk lipids supported its important role on yolk lipid deposition. 25018046 6 108 theme TypeI 1060:1064 arg1 gene 1072:1075 the TypeI VLDLR gene 1056:1075 the TypeI VLDLR gene 1056:1075 However, there was minimal expression of the TypeI VLDLR gene in theca cells and expression was almost undetectable in granulosa cells throughout follicle development. 25018046 3 109 theme RACE 637:640 arg1 method 642:647 the RACE method 633:647 the RACE method 633:647 In the present study, the full-length cDNAs of two splice isoforms of VLDLR were obtained from geese (Anser cygnoide) ovaries using the RACE method. 25018046 5 110 theme theca 910:914 arg1 cells 930:934 theca and granulosa cells 910:934 theca and granulosa cells from early stages of follicle development 910:976 TypeII VLDLR was predominantly expressed in the ovary, with greater amounts of mRNA in theca and granulosa cells from early stages of follicle development but decreased during vitellogenesis. 25018046 5 111 theme granulosa 920:928 arg1 cells 930:934 theca and granulosa cells 910:934 theca and granulosa cells from early stages of follicle development 910:976 TypeII VLDLR was predominantly expressed in the ovary, with greater amounts of mRNA in theca and granulosa cells from early stages of follicle development but decreased during vitellogenesis. 25018046 7 112 theme VLDL 1188:1191 arg1 concentrations 1193:1206 Yolk VLDL concentrations 1183:1206 Yolk VLDL concentrations 1183:1206 Yolk VLDL concentrations decreased as stage of development advanced while yolk triglyceride and cholesterol concentrations increased in a follicular size-dependent manner. 25018046 8 113 theme VLDLR 1414:1418 arg1 transcripts 1392:1402 transcripts 1392:1402 transcripts of TypeII VLDLR and yolk lipids 1392:1434 The significant correlations between transcripts of TypeII VLDLR and yolk lipids supported its important role on yolk lipid deposition. 25018046 3 114 theme present 508:514 arg1 study 516:520 the present study 504:520 the present study 504:520 In the present study, the full-length cDNAs of two splice isoforms of VLDLR were obtained from geese (Anser cygnoide) ovaries using the RACE method. 25018046 5 115 from mRNA 902:905 arg1 cells 930:934 theca and granulosa cells 910:934 theca and granulosa cells from early stages of follicle development 910:976 TypeII VLDLR was predominantly expressed in the ovary, with greater amounts of mRNA in theca and granulosa cells from early stages of follicle development but decreased during vitellogenesis. 25018046 5 115 from mRNA 902:905 arg1 stages 947:952 early stages 941:952 early stages of follicle development 941:976 TypeII VLDLR was predominantly expressed in the ovary, with greater amounts of mRNA in theca and granulosa cells from early stages of follicle development but decreased during vitellogenesis. 29187734 3 0 from defects 380:386 arg1 activation 395:404 the activation 391:404 the activation of BCR signaling 391:421 Here we show that lack of Ogt in B-cell development not only causes severe defects in the activation of BCR signaling, but also perturbs B-cell homeostasis by enhancing apoptosis of mature B cells, partly as a result of impaired response to B-cell activating factor. 29187734 4 1 theme Syk 652:654 arg1 interaction 656:666 Syk interaction 652:666 Syk interaction 652:666 O-GlcNAcylation of Lyn at serine 19 is crucial for efficient Lyn activation and Syk interaction in BCR-mediated B-cell activation and expansion. 29187734 5 2 theme germinal 735:742 arg1 GC 752:753 GC 752:753 GC 752:753 Ogt deficiency in germinal center (GC) B cells also results in enhanced apoptosis of GC B cells and memory B cells in an immune response, consequently causing a reduction of antibody levels. 29187734 5 2 theme germinal 735:742 arg1 center 744:749 germinal center 735:749 germinal center (GC) B cells 735:762 Ogt deficiency in germinal center (GC) B cells also results in enhanced apoptosis of GC B cells and memory B cells in an immune response, consequently causing a reduction of antibody levels. 29187734 5 3 theme cells 826:830 arg1 apoptosis 789:797 enhanced apoptosis 780:797 enhanced apoptosis of GC B cells and memory B cells in an immune response 780:852 Ogt deficiency in germinal center (GC) B cells also results in enhanced apoptosis of GC B cells and memory B cells in an immune response, consequently causing a reduction of antibody levels. 29187734 6 4 theme BCR-mediated 1016:1027 arg1 signals 1040:1046 BCR-mediated activation signals 1016:1046 BCR-mediated activation signals 1016:1046 Together, these results demonstrate that B cells rely on O-GlcNAcylation to maintain homeostasis, transduce BCR-mediated activation signals and activate humoral immunity. 29187734 4 5 from activation 637:646 arg1 expansion 706:714 expansion 706:714 expansion 706:714 O-GlcNAcylation of Lyn at serine 19 is crucial for efficient Lyn activation and Syk interaction in BCR-mediated B-cell activation and expansion. 29187734 4 5 from activation 637:646 arg1 activation 691:700 BCR-mediated B-cell activation 671:700 BCR-mediated B-cell activation 671:700 O-GlcNAcylation of Lyn at serine 19 is crucial for efficient Lyn activation and Syk interaction in BCR-mediated B-cell activation and expansion. 29187734 5 6 theme B 824:824 arg1 cells 826:830 memory B cells 817:830 memory B cells 817:830 Ogt deficiency in germinal center (GC) B cells also results in enhanced apoptosis of GC B cells and memory B cells in an immune response, consequently causing a reduction of antibody levels. 29187734 6 7 theme activation 1029:1038 arg1 signals 1040:1046 BCR-mediated activation signals 1016:1046 BCR-mediated activation signals 1016:1046 Together, these results demonstrate that B cells rely on O-GlcNAcylation to maintain homeostasis, transduce BCR-mediated activation signals and activate humoral immunity. 29187734 2 8 theme reaction 284:291 arg1 unknown 296:302 unknown 296:302 unknown 296:302 O-GlcNAcylation is increased after cross-linking of the B-cell receptor (BCR), but the physiological function of this reaction is unknown. 29187734 2 8 theme reaction 284:291 arg1 function 267:274 the physiological function 249:274 the physiological function of this reaction 249:291 O-GlcNAcylation is increased after cross-linking of the B-cell receptor (BCR), but the physiological function of this reaction is unknown. 29187734 1 9 link O-linked 75:82 arg1 O-GlcNAc 105:112 O-GlcNAc 105:112 O-GlcNAc 105:112 O-linked N-acetylglucosamine (O-GlcNAc) transferase (Ogt) catalyzes O-GlcNAc modification. 29187734 1 9 link O-linked 75:82 arg1 N-acetylglucosamine 84:102 O-linked N-acetylglucosamine 75:102 O-linked N-acetylglucosamine (O-GlcNAc) transferase (Ogt) 75:131 O-linked N-acetylglucosamine (O-GlcNAc) transferase (Ogt) catalyzes O-GlcNAc modification. 29187734 5 10 theme antibody 891:898 arg1 levels 900:905 antibody levels 891:905 antibody levels 891:905 Ogt deficiency in germinal center (GC) B cells also results in enhanced apoptosis of GC B cells and memory B cells in an immune response, consequently causing a reduction of antibody levels. 29187734 4 11 theme BCR-mediated 671:682 arg1 activation 691:700 BCR-mediated B-cell activation 671:700 BCR-mediated B-cell activation 671:700 O-GlcNAcylation of Lyn at serine 19 is crucial for efficient Lyn activation and Syk interaction in BCR-mediated B-cell activation and expansion. 29187734 5 12 theme enhanced 780:787 arg1 apoptosis 789:797 enhanced apoptosis 780:797 enhanced apoptosis of GC B cells and memory B cells in an immune response 780:852 Ogt deficiency in germinal center (GC) B cells also results in enhanced apoptosis of GC B cells and memory B cells in an immune response, consequently causing a reduction of antibody levels. 29187734 5 13 theme B 805:805 arg1 cells 807:811 GC B cells 802:811 GC B cells 802:811 Ogt deficiency in germinal center (GC) B cells also results in enhanced apoptosis of GC B cells and memory B cells in an immune response, consequently causing a reduction of antibody levels. 29187734 3 14 theme cells 496:500 arg1 apoptosis 474:482 apoptosis 474:482 apoptosis of mature B cells 474:500 Here we show that lack of Ogt in B-cell development not only causes severe defects in the activation of BCR signaling, but also perturbs B-cell homeostasis by enhancing apoptosis of mature B cells, partly as a result of impaired response to B-cell activating factor. 29187734 5 15 theme cells 807:811 arg1 apoptosis 789:797 enhanced apoptosis 780:797 enhanced apoptosis of GC B cells and memory B cells in an immune response 780:852 Ogt deficiency in germinal center (GC) B cells also results in enhanced apoptosis of GC B cells and memory B cells in an immune response, consequently causing a reduction of antibody levels. 29187734 3 16 theme BCR 409:411 arg1 signaling 413:421 BCR signaling 409:421 BCR signaling 409:421 Here we show that lack of Ogt in B-cell development not only causes severe defects in the activation of BCR signaling, but also perturbs B-cell homeostasis by enhancing apoptosis of mature B cells, partly as a result of impaired response to B-cell activating factor. 29187734 3 17 theme Ogt 331:333 arg1 lack 323:326 lack 323:326 lack of Ogt in B-cell development 323:355 Here we show that lack of Ogt in B-cell development not only causes severe defects in the activation of BCR signaling, but also perturbs B-cell homeostasis by enhancing apoptosis of mature B cells, partly as a result of impaired response to B-cell activating factor. 29187734 5 18 theme center 744:749 arg1 cells 758:762 germinal center (GC) B cells 735:762 germinal center (GC) B cells 735:762 Ogt deficiency in germinal center (GC) B cells also results in enhanced apoptosis of GC B cells and memory B cells in an immune response, consequently causing a reduction of antibody levels. 29187734 1 19 theme O-linked 75:82 arg1 O-GlcNAc 105:112 O-GlcNAc 105:112 O-GlcNAc 105:112 O-linked N-acetylglucosamine (O-GlcNAc) transferase (Ogt) catalyzes O-GlcNAc modification. 29187734 1 19 theme O-linked 75:82 arg1 N-acetylglucosamine 84:102 O-linked N-acetylglucosamine 75:102 O-linked N-acetylglucosamine (O-GlcNAc) transferase (Ogt) 75:131 O-linked N-acetylglucosamine (O-GlcNAc) transferase (Ogt) catalyzes O-GlcNAc modification. 29187734 3 20 theme signaling 413:421 arg1 activation 395:404 the activation 391:404 the activation of BCR signaling 391:421 Here we show that lack of Ogt in B-cell development not only causes severe defects in the activation of BCR signaling, but also perturbs B-cell homeostasis by enhancing apoptosis of mature B cells, partly as a result of impaired response to B-cell activating factor. 29187734 5 21 theme B 756:756 arg1 cells 758:762 germinal center (GC) B cells 735:762 germinal center (GC) B cells 735:762 Ogt deficiency in germinal center (GC) B cells also results in enhanced apoptosis of GC B cells and memory B cells in an immune response, consequently causing a reduction of antibody levels. 29187734 1 22 theme N-acetylglucosamine 84:102 arg1 Ogt 128:130 Ogt 128:130 Ogt 128:130 O-linked N-acetylglucosamine (O-GlcNAc) transferase (Ogt) catalyzes O-GlcNAc modification. 29187734 1 22 theme N-acetylglucosamine 84:102 arg1 transferase 115:125 O-linked N-acetylglucosamine (O-GlcNAc) transferase 75:125 O-linked N-acetylglucosamine (O-GlcNAc) transferase (Ogt) 75:131 O-linked N-acetylglucosamine (O-GlcNAc) transferase (Ogt) catalyzes O-GlcNAc modification. 29187734 4 23 theme efficient 623:631 arg1 activation 637:646 efficient Lyn activation 623:646 efficient Lyn activation 623:646 O-GlcNAcylation of Lyn at serine 19 is crucial for efficient Lyn activation and Syk interaction in BCR-mediated B-cell activation and expansion. 29187734 6 24 theme B 949:949 arg1 cells 951:955 B cells 949:955 B cells 949:955 Together, these results demonstrate that B cells rely on O-GlcNAcylation to maintain homeostasis, transduce BCR-mediated activation signals and activate humoral immunity. 29187734 5 25 from deficiency 721:730 arg1 cells 758:762 germinal center (GC) B cells 735:762 germinal center (GC) B cells 735:762 Ogt deficiency in germinal center (GC) B cells also results in enhanced apoptosis of GC B cells and memory B cells in an immune response, consequently causing a reduction of antibody levels. 29187734 5 26 theme GC 802:803 arg1 cells 807:811 GC B cells 802:811 GC B cells 802:811 Ogt deficiency in germinal center (GC) B cells also results in enhanced apoptosis of GC B cells and memory B cells in an immune response, consequently causing a reduction of antibody levels. 29187734 3 27 theme impaired 525:532 arg1 response 534:541 impaired response 525:541 impaired response to B-cell activating factor 525:569 Here we show that lack of Ogt in B-cell development not only causes severe defects in the activation of BCR signaling, but also perturbs B-cell homeostasis by enhancing apoptosis of mature B cells, partly as a result of impaired response to B-cell activating factor. 29187734 4 28 from serine 598:603 arg1 O-GlcNAcylation 572:586 O-GlcNAcylation 572:586 O-GlcNAcylation of Lyn at serine 19 572:606 O-GlcNAcylation of Lyn at serine 19 is crucial for efficient Lyn activation and Syk interaction in BCR-mediated B-cell activation and expansion. 29187734 5 29 theme levels 900:905 arg1 reduction 878:886 a reduction 876:886 a reduction of antibody levels 876:905 Ogt deficiency in germinal center (GC) B cells also results in enhanced apoptosis of GC B cells and memory B cells in an immune response, consequently causing a reduction of antibody levels. 29187734 4 30 theme Lyn 591:593 arg1 O-GlcNAcylation 572:586 O-GlcNAcylation 572:586 O-GlcNAcylation of Lyn at serine 19 572:606 O-GlcNAcylation of Lyn at serine 19 is crucial for efficient Lyn activation and Syk interaction in BCR-mediated B-cell activation and expansion. 29187734 0 31 theme cell 34:37 arg1 homeostasis 39:49 B cell homeostasis 32:49 B cell homeostasis 32:49 O-GlcNAcylation is required for B cell homeostasis and antibody responses. 29187734 3 32 theme B-cell 546:551 arg1 factor 564:569 B-cell activating factor 546:569 B-cell activating factor 546:569 Here we show that lack of Ogt in B-cell development not only causes severe defects in the activation of BCR signaling, but also perturbs B-cell homeostasis by enhancing apoptosis of mature B cells, partly as a result of impaired response to B-cell activating factor. 29187734 0 33 theme B 32:32 arg1 homeostasis 39:49 B cell homeostasis 32:49 B cell homeostasis 32:49 O-GlcNAcylation is required for B cell homeostasis and antibody responses. 29187734 3 34 theme activating 553:562 arg1 factor 564:569 B-cell activating factor 546:569 B-cell activating factor 546:569 Here we show that lack of Ogt in B-cell development not only causes severe defects in the activation of BCR signaling, but also perturbs B-cell homeostasis by enhancing apoptosis of mature B cells, partly as a result of impaired response to B-cell activating factor. 29187734 5 35 from apoptosis 789:797 arg1 response 845:852 an immune response 835:852 an immune response 835:852 Ogt deficiency in germinal center (GC) B cells also results in enhanced apoptosis of GC B cells and memory B cells in an immune response, consequently causing a reduction of antibody levels. 29187734 3 36 theme severe 373:378 arg1 defects 380:386 severe defects 373:386 severe defects in the activation of BCR signaling 373:421 Here we show that lack of Ogt in B-cell development not only causes severe defects in the activation of BCR signaling, but also perturbs B-cell homeostasis by enhancing apoptosis of mature B cells, partly as a result of impaired response to B-cell activating factor. 29187734 5 37 theme memory 817:822 arg1 cells 826:830 memory B cells 817:830 memory B cells 817:830 Ogt deficiency in germinal center (GC) B cells also results in enhanced apoptosis of GC B cells and memory B cells in an immune response, consequently causing a reduction of antibody levels. 29187734 3 38 theme response 534:541 arg1 result 515:520 a result 513:520 a result of impaired response to B-cell activating factor 513:569 Here we show that lack of Ogt in B-cell development not only causes severe defects in the activation of BCR signaling, but also perturbs B-cell homeostasis by enhancing apoptosis of mature B cells, partly as a result of impaired response to B-cell activating factor. 29187734 3 38 theme response 534:541 arg1 homeostasis 449:459 B-cell homeostasis 442:459 B-cell homeostasis 442:459 Here we show that lack of Ogt in B-cell development not only causes severe defects in the activation of BCR signaling, but also perturbs B-cell homeostasis by enhancing apoptosis of mature B cells, partly as a result of impaired response to B-cell activating factor. 29187734 6 39 theme humoral 1061:1067 arg1 immunity 1069:1076 humoral immunity 1061:1076 humoral immunity 1061:1076 Together, these results demonstrate that B cells rely on O-GlcNAcylation to maintain homeostasis, transduce BCR-mediated activation signals and activate humoral immunity. 29187734 2 40 theme B-cell 222:227 arg1 BCR 239:241 BCR 239:241 BCR 239:241 O-GlcNAcylation is increased after cross-linking of the B-cell receptor (BCR), but the physiological function of this reaction is unknown. 29187734 2 40 theme B-cell 222:227 arg1 receptor 229:236 B-cell receptor 222:236 the B-cell receptor (BCR) 218:242 O-GlcNAcylation is increased after cross-linking of the B-cell receptor (BCR), but the physiological function of this reaction is unknown. 29187734 2 41 theme receptor 229:236 arg1 cross-linking 201:213 cross-linking 201:213 cross-linking of the B-cell receptor (BCR) 201:242 O-GlcNAcylation is increased after cross-linking of the B-cell receptor (BCR), but the physiological function of this reaction is unknown. 29187734 5 42 theme immune 838:843 arg1 response 845:852 an immune response 835:852 an immune response 835:852 Ogt deficiency in germinal center (GC) B cells also results in enhanced apoptosis of GC B cells and memory B cells in an immune response, consequently causing a reduction of antibody levels. 29187734 2 43 theme physiological 253:265 arg1 unknown 296:302 unknown 296:302 unknown 296:302 O-GlcNAcylation is increased after cross-linking of the B-cell receptor (BCR), but the physiological function of this reaction is unknown. 29187734 2 43 theme physiological 253:265 arg1 function 267:274 the physiological function 249:274 the physiological function of this reaction 249:291 O-GlcNAcylation is increased after cross-linking of the B-cell receptor (BCR), but the physiological function of this reaction is unknown. 29187734 4 44 theme Lyn 633:635 arg1 activation 637:646 efficient Lyn activation 623:646 efficient Lyn activation 623:646 O-GlcNAcylation of Lyn at serine 19 is crucial for efficient Lyn activation and Syk interaction in BCR-mediated B-cell activation and expansion. 29187734 3 45 theme B-cell 442:447 arg1 result 515:520 a result 513:520 a result of impaired response to B-cell activating factor 513:569 Here we show that lack of Ogt in B-cell development not only causes severe defects in the activation of BCR signaling, but also perturbs B-cell homeostasis by enhancing apoptosis of mature B cells, partly as a result of impaired response to B-cell activating factor. 29187734 3 45 theme B-cell 442:447 arg1 homeostasis 449:459 B-cell homeostasis 442:459 B-cell homeostasis 442:459 Here we show that lack of Ogt in B-cell development not only causes severe defects in the activation of BCR signaling, but also perturbs B-cell homeostasis by enhancing apoptosis of mature B cells, partly as a result of impaired response to B-cell activating factor. 29187734 1 46 theme O-GlcNAc 143:150 arg1 modification 152:163 O-GlcNAc modification 143:163 O-GlcNAc modification 143:163 O-linked N-acetylglucosamine (O-GlcNAc) transferase (Ogt) catalyzes O-GlcNAc modification. 29187734 4 47 theme B-cell 684:689 arg1 activation 691:700 BCR-mediated B-cell activation 671:700 BCR-mediated B-cell activation 671:700 O-GlcNAcylation of Lyn at serine 19 is crucial for efficient Lyn activation and Syk interaction in BCR-mediated B-cell activation and expansion. 29187734 5 48 theme Ogt 717:719 arg1 deficiency 721:730 Ogt deficiency 717:730 Ogt deficiency in germinal center (GC) B cells 717:762 Ogt deficiency in germinal center (GC) B cells also results in enhanced apoptosis of GC B cells and memory B cells in an immune response, consequently causing a reduction of antibody levels. 29187734 3 49 from lack 323:326 arg1 development 345:355 B-cell development 338:355 B-cell development 338:355 Here we show that lack of Ogt in B-cell development not only causes severe defects in the activation of BCR signaling, but also perturbs B-cell homeostasis by enhancing apoptosis of mature B cells, partly as a result of impaired response to B-cell activating factor. 29187734 3 50 theme mature 487:492 arg1 cells 496:500 mature B cells 487:500 mature B cells 487:500 Here we show that lack of Ogt in B-cell development not only causes severe defects in the activation of BCR signaling, but also perturbs B-cell homeostasis by enhancing apoptosis of mature B cells, partly as a result of impaired response to B-cell activating factor. 29187734 4 51 from interaction 656:666 arg1 expansion 706:714 expansion 706:714 expansion 706:714 O-GlcNAcylation of Lyn at serine 19 is crucial for efficient Lyn activation and Syk interaction in BCR-mediated B-cell activation and expansion. 29187734 4 51 from interaction 656:666 arg1 activation 691:700 BCR-mediated B-cell activation 671:700 BCR-mediated B-cell activation 671:700 O-GlcNAcylation of Lyn at serine 19 is crucial for efficient Lyn activation and Syk interaction in BCR-mediated B-cell activation and expansion. 29187734 0 52 theme antibody 55:62 arg1 responses 64:72 antibody responses 55:72 antibody responses 55:72 O-GlcNAcylation is required for B cell homeostasis and antibody responses. 29187734 3 53 theme B 494:494 arg1 cells 496:500 mature B cells 487:500 mature B cells 487:500 Here we show that lack of Ogt in B-cell development not only causes severe defects in the activation of BCR signaling, but also perturbs B-cell homeostasis by enhancing apoptosis of mature B cells, partly as a result of impaired response to B-cell activating factor. 29187734 3 54 theme B-cell 338:343 arg1 development 345:355 B-cell development 338:355 B-cell development 338:355 Here we show that lack of Ogt in B-cell development not only causes severe defects in the activation of BCR signaling, but also perturbs B-cell homeostasis by enhancing apoptosis of mature B cells, partly as a result of impaired response to B-cell activating factor. 28903359 6 0 theme higher 1000:1005 arg1 levels 1007:1012 higher levels 1000:1012 higher levels of IL-6 and IL-8 1000:1029 Compared with MCRNc, BCG-stimulated MCRsTn secreted higher levels of IL-6 and IL-8 and their secretome induced a stronger IL-6, IL-1β, and TNFα secretion by macrophages, suggesting the induction of a stronger inflammatory response. 28903359 10 1 theme genomic 1755:1761 arg1 instability 1763:1773 genomic instability 1755:1773 genomic instability 1755:1773 These results indicate that the expression of ST6GALNAC1/sTn improves the response to BCG therapy by inducing a stronger macrophage response and alters gene expression towards malignancy and genomic instability, increasing the sensitivity of BC cells to the oxidizing agents released by BCG. 28903359 9 2 theme increased 1499:1507 arg1 expression 1509:1518 an increased expression 1496:1518 an increased expression of several regulatory non coding RNA genes 1496:1561 In MCRsTn,, BCG challenge induced an increased expression of several regulatory non coding RNA genes. 28903359 1 3 theme sialyltransferase 292:308 arg1 ST6GALNAC1 310:319 the sialyltransferase ST6GALNAC1 288:319 the sialyltransferase ST6GALNAC1 288:319 The sialyl-Tn (sTn) antigen is an O-linked carbohydrate chain aberrantly expressed in bladder cancer (BC), whose biosynthesis is mainly controlled by the sialyltransferase ST6GALNAC1. 28903359 1 4 link O-linked 172:179 arg1 chain 194:198 an O-linked carbohydrate chain 169:198 an O-linked carbohydrate chain aberrantly expressed in bladder cancer (BC), whose biosynthesis is mainly controlled by the sialyltransferase ST6GALNAC1 169:319 The sialyl-Tn (sTn) antigen is an O-linked carbohydrate chain aberrantly expressed in bladder cancer (BC), whose biosynthesis is mainly controlled by the sialyltransferase ST6GALNAC1. 28903359 1 4 link O-linked 172:179 arg1 antigen 158:164 The sialyl-Tn (sTn) antigen 138:164 The sialyl-Tn (sTn) antigen 138:164 The sialyl-Tn (sTn) antigen is an O-linked carbohydrate chain aberrantly expressed in bladder cancer (BC), whose biosynthesis is mainly controlled by the sialyltransferase ST6GALNAC1. 28903359 10 5 theme ST6GALNAC1/sTn 1610:1623 arg1 expression 1596:1605 the expression 1592:1605 the expression of ST6GALNAC1/sTn 1592:1623 These results indicate that the expression of ST6GALNAC1/sTn improves the response to BCG therapy by inducing a stronger macrophage response and alters gene expression towards malignancy and genomic instability, increasing the sensitivity of BC cells to the oxidizing agents released by BCG. 28903359 6 6 theme stronger 1148:1155 arg1 response 1170:1177 a stronger inflammatory response 1146:1177 a stronger inflammatory response 1146:1177 Compared with MCRNc, BCG-stimulated MCRsTn secreted higher levels of IL-6 and IL-8 and their secretome induced a stronger IL-6, IL-1β, and TNFα secretion by macrophages, suggesting the induction of a stronger inflammatory response. 28903359 8 7 theme H2O2 1444:1447 arg1 sensitivity 1449:1459 higher H2O2 sensitivity 1437:1459 higher H2O2 sensitivity 1437:1459 Consistently, MCRsTn cells displayed higher H2O2 sensitivity. 28903359 1 8 theme bladder 224:230 arg1 BC 240:241 BC 240:241 BC 240:241 The sialyl-Tn (sTn) antigen is an O-linked carbohydrate chain aberrantly expressed in bladder cancer (BC), whose biosynthesis is mainly controlled by the sialyltransferase ST6GALNAC1. 28903359 1 8 theme bladder 224:230 arg1 cancer 232:237 bladder cancer 224:237 bladder cancer (BC) 224:242 The sialyl-Tn (sTn) antigen is an O-linked carbohydrate chain aberrantly expressed in bladder cancer (BC), whose biosynthesis is mainly controlled by the sialyltransferase ST6GALNAC1. 28903359 0 9 theme Calmette 91:98 arg1 BCG 108:110 BCG 108:110 BCG 108:110 Expression of sialyl-Tn sugar antigen in bladder cancer cells affects response to Bacillus Calmette Guérin (BCG) and to oxidative damage. 28903359 0 9 theme Calmette 91:98 arg1 Guérin 100:105 Bacillus Calmette Guérin 82:105 Bacillus Calmette Guérin (BCG) 82:111 Expression of sialyl-Tn sugar antigen in bladder cancer cells affects response to Bacillus Calmette Guérin (BCG) and to oxidative damage. 28903359 0 10 from Expression 0:9 arg1 cells 56:60 bladder cancer cells 41:60 bladder cancer cells 41:60 Expression of sialyl-Tn sugar antigen in bladder cancer cells affects response to Bacillus Calmette Guérin (BCG) and to oxidative damage. 28903359 6 11 theme inflammatory 1157:1168 arg1 response 1170:1177 a stronger inflammatory response 1146:1177 a stronger inflammatory response 1146:1177 Compared with MCRNc, BCG-stimulated MCRsTn secreted higher levels of IL-6 and IL-8 and their secretome induced a stronger IL-6, IL-1β, and TNFα secretion by macrophages, suggesting the induction of a stronger inflammatory response. 28903359 5 12 theme line 875:878 arg1 MCR 880:882 the BC cell line MCR 863:882 the BC cell line MCR 863:882 To investigate the role of sTn in BC cell biology and BCG response, we established the cell lines MCRsTn and MCRNc by retroviral transduction of the BC cell line MCR with the ST6GALNAC1 cDNA or with an empty vector, respectively. 28903359 4 13 theme tumor 612:616 arg1 tissues 618:624 tumor tissues 612:624 tumor tissues 612:624 By analyzing tumor tissues, we showed that patients with high ST6GALNAC1 and IL-6 mRNA expression were BCG responders. 28903359 0 14 theme Bacillus 82:89 arg1 BCG 108:110 BCG 108:110 BCG 108:110 Expression of sialyl-Tn sugar antigen in bladder cancer cells affects response to Bacillus Calmette Guérin (BCG) and to oxidative damage. 28903359 0 14 theme Bacillus 82:89 arg1 Guérin 100:105 Bacillus Calmette Guérin 82:105 Bacillus Calmette Guérin (BCG) 82:111 Expression of sialyl-Tn sugar antigen in bladder cancer cells affects response to Bacillus Calmette Guérin (BCG) and to oxidative damage. 28903359 4 15 with patients 642:649 arg1 expression 686:695 high ST6GALNAC1 and IL-6 mRNA expression 656:695 high ST6GALNAC1 and IL-6 mRNA expression 656:695 By analyzing tumor tissues, we showed that patients with high ST6GALNAC1 and IL-6 mRNA expression were BCG responders. 28903359 5 16 theme MCR 880:882 arg1 transduction 847:858 retroviral transduction 836:858 retroviral transduction of the BC cell line MCR with the ST6GALNAC1 cDNA or with an empty vector 836:931 To investigate the role of sTn in BC cell biology and BCG response, we established the cell lines MCRsTn and MCRNc by retroviral transduction of the BC cell line MCR with the ST6GALNAC1 cDNA or with an empty vector, respectively. 28903359 6 17 theme TNFα 1087:1090 arg1 secretion 1092:1100 TNFα secretion 1087:1100 TNFα secretion 1087:1100 Compared with MCRNc, BCG-stimulated MCRsTn secreted higher levels of IL-6 and IL-8 and their secretome induced a stronger IL-6, IL-1β, and TNFα secretion by macrophages, suggesting the induction of a stronger inflammatory response. 28903359 4 18 theme BCG 702:704 arg1 responders 706:715 BCG responders 702:715 BCG responders 702:715 By analyzing tumor tissues, we showed that patients with high ST6GALNAC1 and IL-6 mRNA expression were BCG responders. 28903359 6 19 theme IL-6 1017:1020 arg1 levels 1007:1012 higher levels 1000:1012 higher levels of IL-6 and IL-8 1000:1029 Compared with MCRNc, BCG-stimulated MCRsTn secreted higher levels of IL-6 and IL-8 and their secretome induced a stronger IL-6, IL-1β, and TNFα secretion by macrophages, suggesting the induction of a stronger inflammatory response. 28903359 10 20 theme BCG 1650:1652 arg1 therapy 1654:1660 BCG therapy 1650:1660 BCG therapy 1650:1660 These results indicate that the expression of ST6GALNAC1/sTn improves the response to BCG therapy by inducing a stronger macrophage response and alters gene expression towards malignancy and genomic instability, increasing the sensitivity of BC cells to the oxidizing agents released by BCG. 28903359 7 21 theme MCRNc 1207:1211 arg1 analysis 1195:1202 Transcriptomic analysis 1180:1202 Transcriptomic analysis of MCRNc and MCRsTn 1180:1222 Transcriptomic analysis of MCRNc and MCRsTn revealed that ST6GALNAC1/sTn expression modulates hundreds of genes towards a putative more malignant phenotype and down-regulates several genes maintaining genomic stability. 28903359 10 22 theme macrophage 1685:1694 arg1 response 1696:1703 a stronger macrophage response 1674:1703 a stronger macrophage response 1674:1703 These results indicate that the expression of ST6GALNAC1/sTn improves the response to BCG therapy by inducing a stronger macrophage response and alters gene expression towards malignancy and genomic instability, increasing the sensitivity of BC cells to the oxidizing agents released by BCG. 28903359 1 23 theme sialyl-Tn 142:150 arg1 chain 194:198 an O-linked carbohydrate chain 169:198 an O-linked carbohydrate chain aberrantly expressed in bladder cancer (BC), whose biosynthesis is mainly controlled by the sialyltransferase ST6GALNAC1 169:319 The sialyl-Tn (sTn) antigen is an O-linked carbohydrate chain aberrantly expressed in bladder cancer (BC), whose biosynthesis is mainly controlled by the sialyltransferase ST6GALNAC1. 28903359 1 23 theme sialyl-Tn 142:150 arg1 antigen 158:164 The sialyl-Tn (sTn) antigen 138:164 The sialyl-Tn (sTn) antigen 138:164 The sialyl-Tn (sTn) antigen is an O-linked carbohydrate chain aberrantly expressed in bladder cancer (BC), whose biosynthesis is mainly controlled by the sialyltransferase ST6GALNAC1. 28903359 5 24 with transduction 847:858 arg1 vector 926:931 an empty vector 917:931 an empty vector 917:931 To investigate the role of sTn in BC cell biology and BCG response, we established the cell lines MCRsTn and MCRNc by retroviral transduction of the BC cell line MCR with the ST6GALNAC1 cDNA or with an empty vector, respectively. 28903359 5 24 with transduction 847:858 arg1 cDNA 904:907 the ST6GALNAC1 cDNA 889:907 the ST6GALNAC1 cDNA 889:907 To investigate the role of sTn in BC cell biology and BCG response, we established the cell lines MCRsTn and MCRNc by retroviral transduction of the BC cell line MCR with the ST6GALNAC1 cDNA or with an empty vector, respectively. 28903359 3 25 theme understood 488:497 arg1 correlation 499:509 A poorly understood correlation 479:509 A poorly understood correlation between the expression of sTn and BC patient's response to BCG 479:572 A poorly understood correlation between the expression of sTn and BC patient's response to BCG was previously observed. 28903359 6 26 theme BCG-stimulated 969:982 arg1 MCRsTn 984:989 BCG-stimulated MCRsTn 969:989 BCG-stimulated MCRsTn secreted higher levels of IL-6 and IL-8 969:1029 Compared with MCRNc, BCG-stimulated MCRsTn secreted higher levels of IL-6 and IL-8 and their secretome induced a stronger IL-6, IL-1β, and TNFα secretion by macrophages, suggesting the induction of a stronger inflammatory response. 28903359 2 27 theme superficial 417:427 arg1 BC 429:430 superficial BC 417:430 superficial BC 417:430 Treatment with Bacillus Calmette-Guérin (BCG) is the most effective adjuvant immunotherapy for superficial BC but one third of the patients fail to respond. 28903359 7 28 theme genomic 1381:1387 arg1 stability 1389:1397 genomic stability 1381:1397 genomic stability 1381:1397 Transcriptomic analysis of MCRNc and MCRsTn revealed that ST6GALNAC1/sTn expression modulates hundreds of genes towards a putative more malignant phenotype and down-regulates several genes maintaining genomic stability. 28903359 4 29 theme mRNA 681:684 arg1 expression 686:695 high ST6GALNAC1 and IL-6 mRNA expression 656:695 high ST6GALNAC1 and IL-6 mRNA expression 656:695 By analyzing tumor tissues, we showed that patients with high ST6GALNAC1 and IL-6 mRNA expression were BCG responders. 28903359 1 30 theme sTn 153:155 arg1 chain 194:198 an O-linked carbohydrate chain 169:198 an O-linked carbohydrate chain aberrantly expressed in bladder cancer (BC), whose biosynthesis is mainly controlled by the sialyltransferase ST6GALNAC1 169:319 The sialyl-Tn (sTn) antigen is an O-linked carbohydrate chain aberrantly expressed in bladder cancer (BC), whose biosynthesis is mainly controlled by the sialyltransferase ST6GALNAC1. 28903359 1 30 theme sTn 153:155 arg1 antigen 158:164 The sialyl-Tn (sTn) antigen 138:164 The sialyl-Tn (sTn) antigen 138:164 The sialyl-Tn (sTn) antigen is an O-linked carbohydrate chain aberrantly expressed in bladder cancer (BC), whose biosynthesis is mainly controlled by the sialyltransferase ST6GALNAC1. 28903359 7 31 theme several 1355:1361 arg1 genes 1363:1367 several genes 1355:1367 several genes maintaining genomic stability 1355:1397 Transcriptomic analysis of MCRNc and MCRsTn revealed that ST6GALNAC1/sTn expression modulates hundreds of genes towards a putative more malignant phenotype and down-regulates several genes maintaining genomic stability. 28903359 9 32 theme genes 1557:1561 arg1 expression 1509:1518 an increased expression 1496:1518 an increased expression of several regulatory non coding RNA genes 1496:1561 In MCRsTn,, BCG challenge induced an increased expression of several regulatory non coding RNA genes. 28903359 3 33 theme sTn 537:539 arg1 expression 523:532 the expression 519:532 the expression of sTn 519:539 A poorly understood correlation between the expression of sTn and BC patient's response to BCG was previously observed. 28903359 3 33 theme sTn 537:539 arg1 response 558:565 BC patient's response 545:565 BC patient's response to BCG 545:572 A poorly understood correlation between the expression of sTn and BC patient's response to BCG was previously observed. 28903359 6 34 theme response 1170:1177 arg1 induction 1133:1141 the induction 1129:1141 the induction of a stronger inflammatory response 1129:1177 Compared with MCRNc, BCG-stimulated MCRsTn secreted higher levels of IL-6 and IL-8 and their secretome induced a stronger IL-6, IL-1β, and TNFα secretion by macrophages, suggesting the induction of a stronger inflammatory response. 28903359 0 35 theme sugar 24:28 arg1 antigen 30:36 sialyl-Tn sugar antigen 14:36 sialyl-Tn sugar antigen 14:36 Expression of sialyl-Tn sugar antigen in bladder cancer cells affects response to Bacillus Calmette Guérin (BCG) and to oxidative damage. 28903359 4 36 theme IL-6 676:679 arg1 expression 686:695 high ST6GALNAC1 and IL-6 mRNA expression 656:695 high ST6GALNAC1 and IL-6 mRNA expression 656:695 By analyzing tumor tissues, we showed that patients with high ST6GALNAC1 and IL-6 mRNA expression were BCG responders. 28903359 7 37 theme genes 1286:1290 arg1 hundreds 1274:1281 hundreds 1274:1281 hundreds of genes towards a putative more malignant phenotype 1274:1334 Transcriptomic analysis of MCRNc and MCRsTn revealed that ST6GALNAC1/sTn expression modulates hundreds of genes towards a putative more malignant phenotype and down-regulates several genes maintaining genomic stability. 28903359 5 38 theme BC 867:868 arg1 MCR 880:882 the BC cell line MCR 863:882 the BC cell line MCR 863:882 To investigate the role of sTn in BC cell biology and BCG response, we established the cell lines MCRsTn and MCRNc by retroviral transduction of the BC cell line MCR with the ST6GALNAC1 cDNA or with an empty vector, respectively. 28903359 8 39 theme higher 1437:1442 arg1 sensitivity 1449:1459 higher H2O2 sensitivity 1437:1459 higher H2O2 sensitivity 1437:1459 Consistently, MCRsTn cells displayed higher H2O2 sensitivity. 28903359 2 40 theme effective 380:388 arg1 Treatment 322:330 Treatment 322:330 Treatment with Bacillus Calmette-Guérin (BCG) 322:366 Treatment with Bacillus Calmette-Guérin (BCG) is the most effective adjuvant immunotherapy for superficial BC but one third of the patients fail to respond. 28903359 2 40 theme effective 380:388 arg1 immunotherapy 399:411 the most effective adjuvant immunotherapy 371:411 the most effective adjuvant immunotherapy for superficial BC 371:430 Treatment with Bacillus Calmette-Guérin (BCG) is the most effective adjuvant immunotherapy for superficial BC but one third of the patients fail to respond. 28903359 2 41 theme adjuvant 390:397 arg1 Treatment 322:330 Treatment 322:330 Treatment with Bacillus Calmette-Guérin (BCG) 322:366 Treatment with Bacillus Calmette-Guérin (BCG) is the most effective adjuvant immunotherapy for superficial BC but one third of the patients fail to respond. 28903359 2 41 theme adjuvant 390:397 arg1 immunotherapy 399:411 the most effective adjuvant immunotherapy 371:411 the most effective adjuvant immunotherapy for superficial BC 371:430 Treatment with Bacillus Calmette-Guérin (BCG) is the most effective adjuvant immunotherapy for superficial BC but one third of the patients fail to respond. 28903359 5 42 theme cell 870:873 arg1 MCR 880:882 the BC cell line MCR 863:882 the BC cell line MCR 863:882 To investigate the role of sTn in BC cell biology and BCG response, we established the cell lines MCRsTn and MCRNc by retroviral transduction of the BC cell line MCR with the ST6GALNAC1 cDNA or with an empty vector, respectively. 28903359 7 43 theme malignant 1316:1324 arg1 phenotype 1326:1334 a putative more malignant phenotype 1300:1334 a putative more malignant phenotype 1300:1334 Transcriptomic analysis of MCRNc and MCRsTn revealed that ST6GALNAC1/sTn expression modulates hundreds of genes towards a putative more malignant phenotype and down-regulates several genes maintaining genomic stability. 28903359 6 44 dep stronger 1061:1068 arg1 IL-6 1070:1073 IL-6 1070:1073 IL-6 1070:1073 Compared with MCRNc, BCG-stimulated MCRsTn secreted higher levels of IL-6 and IL-8 and their secretome induced a stronger IL-6, IL-1β, and TNFα secretion by macrophages, suggesting the induction of a stronger inflammatory response. 28903359 6 44 dep stronger 1061:1068 arg1 secretion 1092:1100 TNFα secretion 1087:1100 TNFα secretion 1087:1100 Compared with MCRNc, BCG-stimulated MCRsTn secreted higher levels of IL-6 and IL-8 and their secretome induced a stronger IL-6, IL-1β, and TNFα secretion by macrophages, suggesting the induction of a stronger inflammatory response. 28903359 6 44 dep stronger 1061:1068 arg1 IL-1β 1076:1080 IL-1β 1076:1080 IL-1β 1076:1080 Compared with MCRNc, BCG-stimulated MCRsTn secreted higher levels of IL-6 and IL-8 and their secretome induced a stronger IL-6, IL-1β, and TNFα secretion by macrophages, suggesting the induction of a stronger inflammatory response. 28903359 10 45 theme gene 1716:1719 arg1 expression 1721:1730 gene expression 1716:1730 gene expression 1716:1730 These results indicate that the expression of ST6GALNAC1/sTn improves the response to BCG therapy by inducing a stronger macrophage response and alters gene expression towards malignancy and genomic instability, increasing the sensitivity of BC cells to the oxidizing agents released by BCG. 28903359 7 46 theme Transcriptomic 1180:1193 arg1 analysis 1195:1202 Transcriptomic analysis 1180:1202 Transcriptomic analysis of MCRNc and MCRsTn 1180:1222 Transcriptomic analysis of MCRNc and MCRsTn revealed that ST6GALNAC1/sTn expression modulates hundreds of genes towards a putative more malignant phenotype and down-regulates several genes maintaining genomic stability. 28903359 9 47 theme several 1523:1529 arg1 genes 1557:1561 several regulatory non coding RNA genes 1523:1561 several regulatory non coding RNA genes 1523:1561 In MCRsTn,, BCG challenge induced an increased expression of several regulatory non coding RNA genes. 28903359 7 48 theme MCRsTn 1217:1222 arg1 analysis 1195:1202 Transcriptomic analysis 1180:1202 Transcriptomic analysis of MCRNc and MCRsTn 1180:1222 Transcriptomic analysis of MCRNc and MCRsTn revealed that ST6GALNAC1/sTn expression modulates hundreds of genes towards a putative more malignant phenotype and down-regulates several genes maintaining genomic stability. 28903359 5 49 theme BCG 772:774 arg1 response 776:783 BCG response 772:783 BCG response 772:783 To investigate the role of sTn in BC cell biology and BCG response, we established the cell lines MCRsTn and MCRNc by retroviral transduction of the BC cell line MCR with the ST6GALNAC1 cDNA or with an empty vector, respectively. 28903359 0 50 theme antigen 30:36 arg1 Expression 0:9 Expression 0:9 Expression of sialyl-Tn sugar antigen in bladder cancer cells 0:60 Expression of sialyl-Tn sugar antigen in bladder cancer cells affects response to Bacillus Calmette Guérin (BCG) and to oxidative damage. 28903359 5 51 dep lines 810:814 arg1 MCRsTn 816:821 MCRsTn 816:821 MCRsTn 816:821 To investigate the role of sTn in BC cell biology and BCG response, we established the cell lines MCRsTn and MCRNc by retroviral transduction of the BC cell line MCR with the ST6GALNAC1 cDNA or with an empty vector, respectively. 28903359 5 51 dep lines 810:814 arg1 lines 810:814 the cell lines MCRsTn and MCRNc 801:831 the cell lines MCRsTn and MCRNc 801:831 To investigate the role of sTn in BC cell biology and BCG response, we established the cell lines MCRsTn and MCRNc by retroviral transduction of the BC cell line MCR with the ST6GALNAC1 cDNA or with an empty vector, respectively. 28903359 5 51 dep lines 810:814 arg1 MCRNc 827:831 MCRNc 827:831 MCRNc 827:831 To investigate the role of sTn in BC cell biology and BCG response, we established the cell lines MCRsTn and MCRNc by retroviral transduction of the BC cell line MCR with the ST6GALNAC1 cDNA or with an empty vector, respectively. 28903359 10 52 theme BC 1806:1807 arg1 cells 1809:1813 BC cells 1806:1813 BC cells 1806:1813 These results indicate that the expression of ST6GALNAC1/sTn improves the response to BCG therapy by inducing a stronger macrophage response and alters gene expression towards malignancy and genomic instability, increasing the sensitivity of BC cells to the oxidizing agents released by BCG. 28903359 5 53 theme BC 752:753 arg1 biology 760:766 BC cell biology 752:766 BC cell biology 752:766 To investigate the role of sTn in BC cell biology and BCG response, we established the cell lines MCRsTn and MCRNc by retroviral transduction of the BC cell line MCR with the ST6GALNAC1 cDNA or with an empty vector, respectively. 28903359 1 54 theme O-linked 172:179 arg1 chain 194:198 an O-linked carbohydrate chain 169:198 an O-linked carbohydrate chain aberrantly expressed in bladder cancer (BC), whose biosynthesis is mainly controlled by the sialyltransferase ST6GALNAC1 169:319 The sialyl-Tn (sTn) antigen is an O-linked carbohydrate chain aberrantly expressed in bladder cancer (BC), whose biosynthesis is mainly controlled by the sialyltransferase ST6GALNAC1. 28903359 1 54 theme O-linked 172:179 arg1 antigen 158:164 The sialyl-Tn (sTn) antigen 138:164 The sialyl-Tn (sTn) antigen 138:164 The sialyl-Tn (sTn) antigen is an O-linked carbohydrate chain aberrantly expressed in bladder cancer (BC), whose biosynthesis is mainly controlled by the sialyltransferase ST6GALNAC1. 28903359 0 55 theme cancer 49:54 arg1 cells 56:60 bladder cancer cells 41:60 bladder cancer cells 41:60 Expression of sialyl-Tn sugar antigen in bladder cancer cells affects response to Bacillus Calmette Guérin (BCG) and to oxidative damage. 28903359 9 56 theme regulatory 1531:1540 arg1 genes 1557:1561 several regulatory non coding RNA genes 1523:1561 several regulatory non coding RNA genes 1523:1561 In MCRsTn,, BCG challenge induced an increased expression of several regulatory non coding RNA genes. 28903359 9 57 theme non 1542:1544 arg1 genes 1557:1561 several regulatory non coding RNA genes 1523:1561 several regulatory non coding RNA genes 1523:1561 In MCRsTn,, BCG challenge induced an increased expression of several regulatory non coding RNA genes. 28903359 4 58 theme high 656:659 arg1 expression 686:695 high ST6GALNAC1 and IL-6 mRNA expression 656:695 high ST6GALNAC1 and IL-6 mRNA expression 656:695 By analyzing tumor tissues, we showed that patients with high ST6GALNAC1 and IL-6 mRNA expression were BCG responders. 28903359 0 59 theme bladder 41:47 arg1 cells 56:60 bladder cancer cells 41:60 bladder cancer cells 41:60 Expression of sialyl-Tn sugar antigen in bladder cancer cells affects response to Bacillus Calmette Guérin (BCG) and to oxidative damage. 28903359 0 60 theme oxidative 120:128 arg1 damage 130:135 oxidative damage 120:135 oxidative damage 120:135 Expression of sialyl-Tn sugar antigen in bladder cancer cells affects response to Bacillus Calmette Guérin (BCG) and to oxidative damage. 28903359 2 61 with Treatment 322:330 arg1 BCG 363:365 BCG 363:365 BCG 363:365 Treatment with Bacillus Calmette-Guérin (BCG) is the most effective adjuvant immunotherapy for superficial BC but one third of the patients fail to respond. 28903359 2 61 with Treatment 322:330 arg1 Calmette-Guérin 346:360 Bacillus Calmette-Guérin 337:360 Bacillus Calmette-Guérin (BCG) 337:366 Treatment with Bacillus Calmette-Guérin (BCG) is the most effective adjuvant immunotherapy for superficial BC but one third of the patients fail to respond. 28903359 3 62 theme BC 545:546 arg1 patient 548:554 BC patient's 545:556 BC patient's response to BCG 545:572 A poorly understood correlation between the expression of sTn and BC patient's response to BCG was previously observed. 28903359 6 63 theme IL-8 1026:1029 arg1 levels 1007:1012 higher levels 1000:1012 higher levels of IL-6 and IL-8 1000:1029 Compared with MCRNc, BCG-stimulated MCRsTn secreted higher levels of IL-6 and IL-8 and their secretome induced a stronger IL-6, IL-1β, and TNFα secretion by macrophages, suggesting the induction of a stronger inflammatory response. 28903359 9 64 theme RNA 1553:1555 arg1 genes 1557:1561 several regulatory non coding RNA genes 1523:1561 several regulatory non coding RNA genes 1523:1561 In MCRsTn,, BCG challenge induced an increased expression of several regulatory non coding RNA genes. 28903359 5 65 theme ST6GALNAC1 893:902 arg1 cDNA 904:907 the ST6GALNAC1 cDNA 889:907 the ST6GALNAC1 cDNA 889:907 To investigate the role of sTn in BC cell biology and BCG response, we established the cell lines MCRsTn and MCRNc by retroviral transduction of the BC cell line MCR with the ST6GALNAC1 cDNA or with an empty vector, respectively. 28903359 5 66 theme empty 920:924 arg1 vector 926:931 an empty vector 917:931 an empty vector 917:931 To investigate the role of sTn in BC cell biology and BCG response, we established the cell lines MCRsTn and MCRNc by retroviral transduction of the BC cell line MCR with the ST6GALNAC1 cDNA or with an empty vector, respectively. 28903359 5 67 theme retroviral 836:845 arg1 transduction 847:858 retroviral transduction 836:858 retroviral transduction of the BC cell line MCR with the ST6GALNAC1 cDNA or with an empty vector 836:931 To investigate the role of sTn in BC cell biology and BCG response, we established the cell lines MCRsTn and MCRNc by retroviral transduction of the BC cell line MCR with the ST6GALNAC1 cDNA or with an empty vector, respectively. 28903359 7 68 theme putative 1302:1309 arg1 phenotype 1326:1334 a putative more malignant phenotype 1300:1334 a putative more malignant phenotype 1300:1334 Transcriptomic analysis of MCRNc and MCRsTn revealed that ST6GALNAC1/sTn expression modulates hundreds of genes towards a putative more malignant phenotype and down-regulates several genes maintaining genomic stability. 28903359 1 69 theme carbohydrate 181:192 arg1 chain 194:198 an O-linked carbohydrate chain 169:198 an O-linked carbohydrate chain aberrantly expressed in bladder cancer (BC), whose biosynthesis is mainly controlled by the sialyltransferase ST6GALNAC1 169:319 The sialyl-Tn (sTn) antigen is an O-linked carbohydrate chain aberrantly expressed in bladder cancer (BC), whose biosynthesis is mainly controlled by the sialyltransferase ST6GALNAC1. 28903359 1 69 theme carbohydrate 181:192 arg1 antigen 158:164 The sialyl-Tn (sTn) antigen 138:164 The sialyl-Tn (sTn) antigen 138:164 The sialyl-Tn (sTn) antigen is an O-linked carbohydrate chain aberrantly expressed in bladder cancer (BC), whose biosynthesis is mainly controlled by the sialyltransferase ST6GALNAC1. 28903359 10 70 theme stronger 1676:1683 arg1 response 1696:1703 a stronger macrophage response 1674:1703 a stronger macrophage response 1674:1703 These results indicate that the expression of ST6GALNAC1/sTn improves the response to BCG therapy by inducing a stronger macrophage response and alters gene expression towards malignancy and genomic instability, increasing the sensitivity of BC cells to the oxidizing agents released by BCG. 28903359 10 71 theme oxidizing 1822:1830 arg1 agents 1832:1837 the oxidizing agents 1818:1837 the oxidizing agents released by BCG 1818:1853 These results indicate that the expression of ST6GALNAC1/sTn improves the response to BCG therapy by inducing a stronger macrophage response and alters gene expression towards malignancy and genomic instability, increasing the sensitivity of BC cells to the oxidizing agents released by BCG. 28903359 5 72 theme cell 755:758 arg1 biology 760:766 BC cell biology 752:766 BC cell biology 752:766 To investigate the role of sTn in BC cell biology and BCG response, we established the cell lines MCRsTn and MCRNc by retroviral transduction of the BC cell line MCR with the ST6GALNAC1 cDNA or with an empty vector, respectively. 28903359 4 73 theme ST6GALNAC1 661:670 arg1 expression 686:695 high ST6GALNAC1 and IL-6 mRNA expression 656:695 high ST6GALNAC1 and IL-6 mRNA expression 656:695 By analyzing tumor tissues, we showed that patients with high ST6GALNAC1 and IL-6 mRNA expression were BCG responders. 28903359 10 74 theme cells 1809:1813 arg1 sensitivity 1791:1801 the sensitivity 1787:1801 the sensitivity of BC cells to the oxidizing agents released by BCG 1787:1853 These results indicate that the expression of ST6GALNAC1/sTn improves the response to BCG therapy by inducing a stronger macrophage response and alters gene expression towards malignancy and genomic instability, increasing the sensitivity of BC cells to the oxidizing agents released by BCG. 28903359 8 75 theme MCRsTn 1414:1419 arg1 cells 1421:1425 MCRsTn cells 1414:1425 MCRsTn cells 1414:1425 Consistently, MCRsTn cells displayed higher H2O2 sensitivity. 28903359 7 76 theme ST6GALNAC1/sTn 1238:1251 arg1 expression 1253:1262 ST6GALNAC1/sTn expression 1238:1262 ST6GALNAC1/sTn expression 1238:1262 Transcriptomic analysis of MCRNc and MCRsTn revealed that ST6GALNAC1/sTn expression modulates hundreds of genes towards a putative more malignant phenotype and down-regulates several genes maintaining genomic stability. 28903359 5 77 theme cell 805:808 arg1 MCRsTn 816:821 MCRsTn 816:821 MCRsTn 816:821 To investigate the role of sTn in BC cell biology and BCG response, we established the cell lines MCRsTn and MCRNc by retroviral transduction of the BC cell line MCR with the ST6GALNAC1 cDNA or with an empty vector, respectively. 28903359 5 77 theme cell 805:808 arg1 lines 810:814 the cell lines MCRsTn and MCRNc 801:831 the cell lines MCRsTn and MCRNc 801:831 To investigate the role of sTn in BC cell biology and BCG response, we established the cell lines MCRsTn and MCRNc by retroviral transduction of the BC cell line MCR with the ST6GALNAC1 cDNA or with an empty vector, respectively. 28903359 5 77 theme cell 805:808 arg1 MCRNc 827:831 MCRNc 827:831 MCRNc 827:831 To investigate the role of sTn in BC cell biology and BCG response, we established the cell lines MCRsTn and MCRNc by retroviral transduction of the BC cell line MCR with the ST6GALNAC1 cDNA or with an empty vector, respectively. 28903359 9 78 theme BCG 1474:1476 arg1 challenge 1478:1486 BCG challenge 1474:1486 BCG challenge 1474:1486 In MCRsTn,, BCG challenge induced an increased expression of several regulatory non coding RNA genes. 28903359 2 79 theme patients 453:460 arg1 third 440:444 third 440:444 third 440:444 Treatment with Bacillus Calmette-Guérin (BCG) is the most effective adjuvant immunotherapy for superficial BC but one third of the patients fail to respond. 28903359 5 80 from role 737:740 arg1 biology 760:766 BC cell biology 752:766 BC cell biology 752:766 To investigate the role of sTn in BC cell biology and BCG response, we established the cell lines MCRsTn and MCRNc by retroviral transduction of the BC cell line MCR with the ST6GALNAC1 cDNA or with an empty vector, respectively. 28903359 5 80 from role 737:740 arg1 response 776:783 BCG response 772:783 BCG response 772:783 To investigate the role of sTn in BC cell biology and BCG response, we established the cell lines MCRsTn and MCRNc by retroviral transduction of the BC cell line MCR with the ST6GALNAC1 cDNA or with an empty vector, respectively. 28903359 0 81 theme sialyl-Tn 14:22 arg1 antigen 30:36 sialyl-Tn sugar antigen 14:36 sialyl-Tn sugar antigen 14:36 Expression of sialyl-Tn sugar antigen in bladder cancer cells affects response to Bacillus Calmette Guérin (BCG) and to oxidative damage. 28903359 5 82 theme sTn 745:747 arg1 role 737:740 the role 733:740 the role of sTn in BC cell biology and BCG response 733:783 To investigate the role of sTn in BC cell biology and BCG response, we established the cell lines MCRsTn and MCRNc by retroviral transduction of the BC cell line MCR with the ST6GALNAC1 cDNA or with an empty vector, respectively. 28903359 9 83 theme coding 1546:1551 arg1 genes 1557:1561 several regulatory non coding RNA genes 1523:1561 several regulatory non coding RNA genes 1523:1561 In MCRsTn,, BCG challenge induced an increased expression of several regulatory non coding RNA genes. 28526214 4 0 from healing 663:669 arg1 condition 683:691 diabetic condition 674:691 diabetic condition 674:691 Previously, we had demonstrated that high glucose environment alters physiologic functions of keratinocytes and contributes to impaired wound healing in diabetic condition. 28526214 5 1 theme diabetics 818:826 arg1 healing 807:813 delayed wound healing 793:813 delayed wound healing of diabetics 793:826 OBJECTIVE In this study, we hypothesized that Gal-7 expression of keratinocytes may be involved in delayed wound healing of diabetics. 28526214 1 2 theme various 281:287 arg1 complications 289:301 various complications 281:301 various complications 281:301 BACKGROUND Diabetes is an important global health issue due to its increasing prevalence and association with various complications. 28526214 5 3 theme keratinocytes 760:772 arg1 expression 746:755 Gal-7 expression 740:755 Gal-7 expression of keratinocytes 740:772 OBJECTIVE In this study, we hypothesized that Gal-7 expression of keratinocytes may be involved in delayed wound healing of diabetics. 28526214 9 4 theme therapeutic 1399:1409 arg1 approach 1411:1418 novel therapeutic approach 1393:1418 novel therapeutic approach to promote wound healing in diabetic patients 1393:1464 CONCLUSION Taken together, restoring the levels of Gal-7 and O-GlcNAc glycosylation may present novel therapeutic approach to promote wound healing in diabetic patients. 28526214 9 5 theme glycosylation 1367:1379 arg1 levels 1338:1343 the levels 1334:1343 the levels of Gal-7 and O-GlcNAc glycosylation 1334:1379 CONCLUSION Taken together, restoring the levels of Gal-7 and O-GlcNAc glycosylation may present novel therapeutic approach to promote wound healing in diabetic patients. 28526214 6 6 theme mice 885:888 arg1 model 890:894 cultured human keratinocytes and diabetic mice model 843:894 cultured human keratinocytes and diabetic mice model 843:894 METHODS Using cultured human keratinocytes and diabetic mice model, the Gal-7 expression was evaluated under high glucose environment. 28526214 9 7 theme Gal-7 1348:1352 arg1 levels 1338:1343 the levels 1334:1343 the levels of Gal-7 and O-GlcNAc glycosylation 1334:1379 CONCLUSION Taken together, restoring the levels of Gal-7 and O-GlcNAc glycosylation may present novel therapeutic approach to promote wound healing in diabetic patients. 28526214 9 8 from healing 1437:1443 arg1 patients 1457:1464 diabetic patients 1448:1464 diabetic patients 1448:1464 CONCLUSION Taken together, restoring the levels of Gal-7 and O-GlcNAc glycosylation may present novel therapeutic approach to promote wound healing in diabetic patients. 28526214 6 9 theme diabetic 876:883 arg1 mice 885:888 diabetic mice 876:888 diabetic mice 876:888 METHODS Using cultured human keratinocytes and diabetic mice model, the Gal-7 expression was evaluated under high glucose environment. 28526214 4 10 theme impaired 648:655 arg1 healing 663:669 impaired wound healing 648:669 impaired wound healing in diabetic condition 648:691 Previously, we had demonstrated that high glucose environment alters physiologic functions of keratinocytes and contributes to impaired wound healing in diabetic condition. 28526214 7 11 theme Gal-7 1035:1039 arg1 expression 1041:1050 Gal-7 expression 1035:1050 Gal-7 expression 1035:1050 RESULTS Our results demonstrated that high-glucose environment reduced Gal-7 expression, a molecule that plays an important role in keratinocyte migration. 28526214 7 11 theme Gal-7 1035:1039 arg1 molecule 1055:1062 a molecule 1053:1062 a molecule that plays an important role in keratinocyte migration 1053:1117 RESULTS Our results demonstrated that high-glucose environment reduced Gal-7 expression, a molecule that plays an important role in keratinocyte migration. 28526214 0 12 theme impaired 138:145 arg1 healing 162:168 impaired diabetic wound healing 138:168 impaired diabetic wound healing 138:168 High-glucose environment induced intracellular O-GlcNAc glycosylation and reduced galectin-7 expression in keratinocytes: Implications on impaired diabetic wound healing. 28526214 8 13 theme high 1271:1274 arg1 environment 1284:1294 high glucose environment 1271:1294 high glucose environment 1271:1294 Additionally, we found that increased O-linked N-Acetyl-glucosamine (O-GlcNAc) is responsible for reduced Gal-7 expression in keratinocytes exposed to high glucose environment. 28526214 6 14 theme keratinocytes 858:870 arg1 model 890:894 cultured human keratinocytes and diabetic mice model 843:894 cultured human keratinocytes and diabetic mice model 843:894 METHODS Using cultured human keratinocytes and diabetic mice model, the Gal-7 expression was evaluated under high glucose environment. 28526214 7 15 dep demonstrated 984:995 arg1 RESULTS 964:970 RESULTS 964:970 RESULTS 964:970 RESULTS Our results demonstrated that high-glucose environment reduced Gal-7 expression, a molecule that plays an important role in keratinocyte migration. 28526214 1 16 theme important 197:205 arg1 Diabetes 182:189 BACKGROUND Diabetes 171:189 BACKGROUND Diabetes 171:189 BACKGROUND Diabetes is an important global health issue due to its increasing prevalence and association with various complications. 28526214 1 16 theme important 197:205 arg1 issue 221:225 an important global health issue 194:225 an important global health issue due to its increasing prevalence and association with various complications 194:301 BACKGROUND Diabetes is an important global health issue due to its increasing prevalence and association with various complications. 28526214 5 17 theme wound 801:805 arg1 healing 807:813 delayed wound healing 793:813 delayed wound healing of diabetics 793:826 OBJECTIVE In this study, we hypothesized that Gal-7 expression of keratinocytes may be involved in delayed wound healing of diabetics. 28526214 6 18 theme glucose 943:949 arg1 environment 951:961 high glucose environment 938:961 high glucose environment 938:961 METHODS Using cultured human keratinocytes and diabetic mice model, the Gal-7 expression was evaluated under high glucose environment. 28526214 6 19 theme human 852:856 arg1 keratinocytes 858:870 cultured human keratinocytes 843:870 cultured human keratinocytes 843:870 METHODS Using cultured human keratinocytes and diabetic mice model, the Gal-7 expression was evaluated under high glucose environment. 28526214 2 20 theme wound 313:317 arg1 complication 340:351 a serious complication 330:351 a serious complication associated with diabetes that frequently results in infection and amputation 330:428 Impaired wound healing is a serious complication associated with diabetes that frequently results in infection and amputation. 28526214 2 20 theme wound 313:317 arg1 healing 319:325 Impaired wound healing 304:325 Impaired wound healing 304:325 Impaired wound healing is a serious complication associated with diabetes that frequently results in infection and amputation. 28526214 1 21 theme global 207:212 arg1 Diabetes 182:189 BACKGROUND Diabetes 171:189 BACKGROUND Diabetes 171:189 BACKGROUND Diabetes is an important global health issue due to its increasing prevalence and association with various complications. 28526214 1 21 theme global 207:212 arg1 issue 221:225 an important global health issue 194:225 an important global health issue due to its increasing prevalence and association with various complications 194:301 BACKGROUND Diabetes is an important global health issue due to its increasing prevalence and association with various complications. 28526214 6 22 theme high 938:941 arg1 environment 951:961 high glucose environment 938:961 high glucose environment 938:961 METHODS Using cultured human keratinocytes and diabetic mice model, the Gal-7 expression was evaluated under high glucose environment. 28526214 8 23 theme increased 1148:1156 arg1 O-GlcNAc 1189:1196 O-GlcNAc 1189:1196 O-GlcNAc 1189:1196 Additionally, we found that increased O-linked N-Acetyl-glucosamine (O-GlcNAc) is responsible for reduced Gal-7 expression in keratinocytes exposed to high glucose environment. 28526214 8 23 theme increased 1148:1156 arg1 N-Acetyl-glucosamine 1167:1186 increased O-linked N-Acetyl-glucosamine 1148:1186 increased O-linked N-Acetyl-glucosamine (O-GlcNAc) 1148:1197 Additionally, we found that increased O-linked N-Acetyl-glucosamine (O-GlcNAc) is responsible for reduced Gal-7 expression in keratinocytes exposed to high glucose environment. 28526214 6 24 theme cultured 843:850 arg1 keratinocytes 858:870 cultured human keratinocytes 843:870 cultured human keratinocytes 843:870 METHODS Using cultured human keratinocytes and diabetic mice model, the Gal-7 expression was evaluated under high glucose environment. 28526214 8 25 link O-linked 1158:1165 arg1 O-GlcNAc 1189:1196 O-GlcNAc 1189:1196 O-GlcNAc 1189:1196 Additionally, we found that increased O-linked N-Acetyl-glucosamine (O-GlcNAc) is responsible for reduced Gal-7 expression in keratinocytes exposed to high glucose environment. 28526214 8 25 link O-linked 1158:1165 arg1 N-Acetyl-glucosamine 1167:1186 increased O-linked N-Acetyl-glucosamine 1148:1186 increased O-linked N-Acetyl-glucosamine (O-GlcNAc) 1148:1197 Additionally, we found that increased O-linked N-Acetyl-glucosamine (O-GlcNAc) is responsible for reduced Gal-7 expression in keratinocytes exposed to high glucose environment. 28526214 1 26 theme health 214:219 arg1 Diabetes 182:189 BACKGROUND Diabetes 171:189 BACKGROUND Diabetes 171:189 BACKGROUND Diabetes is an important global health issue due to its increasing prevalence and association with various complications. 28526214 1 26 theme health 214:219 arg1 issue 221:225 an important global health issue 194:225 an important global health issue due to its increasing prevalence and association with various complications 194:301 BACKGROUND Diabetes is an important global health issue due to its increasing prevalence and association with various complications. 28526214 0 27 theme High-glucose 0:11 arg1 environment 13:23 High-glucose environment 0:23 High-glucose environment 0:23 High-glucose environment induced intracellular O-GlcNAc glycosylation and reduced galectin-7 expression in keratinocytes: Implications on impaired diabetic wound healing. 28526214 0 28 theme intracellular 33:45 arg1 glycosylation 56:68 intracellular O-GlcNAc glycosylation 33:68 intracellular O-GlcNAc glycosylation 33:68 High-glucose environment induced intracellular O-GlcNAc glycosylation and reduced galectin-7 expression in keratinocytes: Implications on impaired diabetic wound healing. 28526214 4 29 theme physiologic 590:600 arg1 functions 602:610 physiologic functions 590:610 physiologic functions of keratinocytes 590:627 Previously, we had demonstrated that high glucose environment alters physiologic functions of keratinocytes and contributes to impaired wound healing in diabetic condition. 28526214 0 30 theme wound 156:160 arg1 healing 162:168 impaired diabetic wound healing 138:168 impaired diabetic wound healing 138:168 High-glucose environment induced intracellular O-GlcNAc glycosylation and reduced galectin-7 expression in keratinocytes: Implications on impaired diabetic wound healing. 28526214 7 31 theme high-glucose 1002:1013 arg1 environment 1015:1025 high-glucose environment 1002:1025 high-glucose environment 1002:1025 RESULTS Our results demonstrated that high-glucose environment reduced Gal-7 expression, a molecule that plays an important role in keratinocyte migration. 28526214 3 32 theme skin 501:504 arg1 healing 512:518 skin wound healing 501:518 skin wound healing 501:518 Galectin-7 (Gal-7) has been reported to play an important role during skin wound healing. 28526214 4 33 theme keratinocytes 615:627 arg1 functions 602:610 physiologic functions 590:610 physiologic functions of keratinocytes 590:627 Previously, we had demonstrated that high glucose environment alters physiologic functions of keratinocytes and contributes to impaired wound healing in diabetic condition. 28526214 0 34 theme diabetic 147:154 arg1 healing 162:168 impaired diabetic wound healing 138:168 impaired diabetic wound healing 138:168 High-glucose environment induced intracellular O-GlcNAc glycosylation and reduced galectin-7 expression in keratinocytes: Implications on impaired diabetic wound healing. 28526214 2 35 theme serious 332:338 arg1 complication 340:351 a serious complication 330:351 a serious complication associated with diabetes that frequently results in infection and amputation 330:428 Impaired wound healing is a serious complication associated with diabetes that frequently results in infection and amputation. 28526214 2 35 theme serious 332:338 arg1 healing 319:325 Impaired wound healing 304:325 Impaired wound healing 304:325 Impaired wound healing is a serious complication associated with diabetes that frequently results in infection and amputation. 28526214 3 36 theme wound 506:510 arg1 healing 512:518 skin wound healing 501:518 skin wound healing 501:518 Galectin-7 (Gal-7) has been reported to play an important role during skin wound healing. 28526214 5 37 dep OBJECTIVE 694:702 arg1 hypothesized 722:733 hypothesized 722:733 hypothesized that Gal-7 expression of keratinocytes may be involved in delayed wound healing of diabetics 722:826 OBJECTIVE In this study, we hypothesized that Gal-7 expression of keratinocytes may be involved in delayed wound healing of diabetics. 28526214 8 38 from expression 1232:1241 arg1 keratinocytes 1246:1258 keratinocytes 1246:1258 keratinocytes exposed to high glucose environment 1246:1294 Additionally, we found that increased O-linked N-Acetyl-glucosamine (O-GlcNAc) is responsible for reduced Gal-7 expression in keratinocytes exposed to high glucose environment. 28526214 8 39 theme O-linked 1158:1165 arg1 O-GlcNAc 1189:1196 O-GlcNAc 1189:1196 O-GlcNAc 1189:1196 Additionally, we found that increased O-linked N-Acetyl-glucosamine (O-GlcNAc) is responsible for reduced Gal-7 expression in keratinocytes exposed to high glucose environment. 28526214 8 39 theme O-linked 1158:1165 arg1 N-Acetyl-glucosamine 1167:1186 increased O-linked N-Acetyl-glucosamine 1148:1186 increased O-linked N-Acetyl-glucosamine (O-GlcNAc) 1148:1197 Additionally, we found that increased O-linked N-Acetyl-glucosamine (O-GlcNAc) is responsible for reduced Gal-7 expression in keratinocytes exposed to high glucose environment. 28526214 0 40 theme O-GlcNAc 47:54 arg1 glycosylation 56:68 intracellular O-GlcNAc glycosylation 33:68 intracellular O-GlcNAc glycosylation 33:68 High-glucose environment induced intracellular O-GlcNAc glycosylation and reduced galectin-7 expression in keratinocytes: Implications on impaired diabetic wound healing. 28526214 4 41 theme glucose 563:569 arg1 environment 571:581 high glucose environment 558:581 high glucose environment 558:581 Previously, we had demonstrated that high glucose environment alters physiologic functions of keratinocytes and contributes to impaired wound healing in diabetic condition. 28526214 0 42 from expression 93:102 arg1 keratinocytes 107:119 keratinocytes 107:119 keratinocytes 107:119 High-glucose environment induced intracellular O-GlcNAc glycosylation and reduced galectin-7 expression in keratinocytes: Implications on impaired diabetic wound healing. 28526214 9 43 theme diabetic 1448:1455 arg1 patients 1457:1464 diabetic patients 1448:1464 diabetic patients 1448:1464 CONCLUSION Taken together, restoring the levels of Gal-7 and O-GlcNAc glycosylation may present novel therapeutic approach to promote wound healing in diabetic patients. 28526214 9 44 theme novel 1393:1397 arg1 approach 1411:1418 novel therapeutic approach 1393:1418 novel therapeutic approach to promote wound healing in diabetic patients 1393:1464 CONCLUSION Taken together, restoring the levels of Gal-7 and O-GlcNAc glycosylation may present novel therapeutic approach to promote wound healing in diabetic patients. 28526214 1 45 theme increasing 238:247 arg1 prevalence 249:258 its increasing prevalence 234:258 its increasing prevalence 234:258 BACKGROUND Diabetes is an important global health issue due to its increasing prevalence and association with various complications. 28526214 4 46 theme high 558:561 arg1 environment 571:581 high glucose environment 558:581 high glucose environment 558:581 Previously, we had demonstrated that high glucose environment alters physiologic functions of keratinocytes and contributes to impaired wound healing in diabetic condition. 28526214 8 47 theme reduced 1218:1224 arg1 expression 1232:1241 reduced Gal-7 expression 1218:1241 reduced Gal-7 expression in keratinocytes exposed to high glucose environment 1218:1294 Additionally, we found that increased O-linked N-Acetyl-glucosamine (O-GlcNAc) is responsible for reduced Gal-7 expression in keratinocytes exposed to high glucose environment. 28526214 7 48 theme keratinocyte 1096:1107 arg1 migration 1109:1117 keratinocyte migration 1096:1117 keratinocyte migration 1096:1117 RESULTS Our results demonstrated that high-glucose environment reduced Gal-7 expression, a molecule that plays an important role in keratinocyte migration. 28526214 6 49 theme Gal-7 901:905 arg1 expression 907:916 the Gal-7 expression 897:916 the Gal-7 expression 897:916 METHODS Using cultured human keratinocytes and diabetic mice model, the Gal-7 expression was evaluated under high glucose environment. 28526214 7 50 theme important 1078:1086 arg1 role 1088:1091 an important role 1075:1091 an important role 1075:1091 RESULTS Our results demonstrated that high-glucose environment reduced Gal-7 expression, a molecule that plays an important role in keratinocyte migration. 28526214 9 51 theme wound 1431:1435 arg1 healing 1437:1443 wound healing 1431:1443 wound healing in diabetic patients 1431:1464 CONCLUSION Taken together, restoring the levels of Gal-7 and O-GlcNAc glycosylation may present novel therapeutic approach to promote wound healing in diabetic patients. 28526214 5 52 theme Gal-7 740:744 arg1 expression 746:755 Gal-7 expression 740:755 Gal-7 expression of keratinocytes 740:772 OBJECTIVE In this study, we hypothesized that Gal-7 expression of keratinocytes may be involved in delayed wound healing of diabetics. 28526214 9 53 theme O-GlcNAc 1358:1365 arg1 glycosylation 1367:1379 O-GlcNAc glycosylation 1358:1379 O-GlcNAc glycosylation 1358:1379 CONCLUSION Taken together, restoring the levels of Gal-7 and O-GlcNAc glycosylation may present novel therapeutic approach to promote wound healing in diabetic patients. 28526214 2 54 theme Impaired 304:311 arg1 complication 340:351 a serious complication 330:351 a serious complication associated with diabetes that frequently results in infection and amputation 330:428 Impaired wound healing is a serious complication associated with diabetes that frequently results in infection and amputation. 28526214 2 54 theme Impaired 304:311 arg1 healing 319:325 Impaired wound healing 304:325 Impaired wound healing 304:325 Impaired wound healing is a serious complication associated with diabetes that frequently results in infection and amputation. 28526214 5 55 theme delayed 793:799 arg1 healing 807:813 delayed wound healing 793:813 delayed wound healing of diabetics 793:826 OBJECTIVE In this study, we hypothesized that Gal-7 expression of keratinocytes may be involved in delayed wound healing of diabetics. 28526214 0 56 from Implications 122:133 arg1 healing 162:168 impaired diabetic wound healing 138:168 impaired diabetic wound healing 138:168 High-glucose environment induced intracellular O-GlcNAc glycosylation and reduced galectin-7 expression in keratinocytes: Implications on impaired diabetic wound healing. 28526214 8 57 theme glucose 1276:1282 arg1 environment 1284:1294 high glucose environment 1271:1294 high glucose environment 1271:1294 Additionally, we found that increased O-linked N-Acetyl-glucosamine (O-GlcNAc) is responsible for reduced Gal-7 expression in keratinocytes exposed to high glucose environment. 28526214 1 58 with association 264:274 arg1 complications 289:301 various complications 281:301 various complications 281:301 BACKGROUND Diabetes is an important global health issue due to its increasing prevalence and association with various complications. 28526214 4 59 theme wound 657:661 arg1 healing 663:669 impaired wound healing 648:669 impaired wound healing in diabetic condition 648:691 Previously, we had demonstrated that high glucose environment alters physiologic functions of keratinocytes and contributes to impaired wound healing in diabetic condition. 28526214 8 60 theme Gal-7 1226:1230 arg1 expression 1232:1241 reduced Gal-7 expression 1218:1241 reduced Gal-7 expression in keratinocytes exposed to high glucose environment 1218:1294 Additionally, we found that increased O-linked N-Acetyl-glucosamine (O-GlcNAc) is responsible for reduced Gal-7 expression in keratinocytes exposed to high glucose environment. 28526214 1 61 theme due 227:229 arg1 Diabetes 182:189 BACKGROUND Diabetes 171:189 BACKGROUND Diabetes 171:189 BACKGROUND Diabetes is an important global health issue due to its increasing prevalence and association with various complications. 28526214 1 61 theme due 227:229 arg1 issue 221:225 an important global health issue 194:225 an important global health issue due to its increasing prevalence and association with various complications 194:301 BACKGROUND Diabetes is an important global health issue due to its increasing prevalence and association with various complications. 28526214 1 62 theme BACKGROUND 171:180 arg1 Diabetes 182:189 BACKGROUND Diabetes 171:189 BACKGROUND Diabetes 171:189 BACKGROUND Diabetes is an important global health issue due to its increasing prevalence and association with various complications. 28526214 1 62 theme BACKGROUND 171:180 arg1 issue 221:225 an important global health issue 194:225 an important global health issue due to its increasing prevalence and association with various complications 194:301 BACKGROUND Diabetes is an important global health issue due to its increasing prevalence and association with various complications. 28526214 3 63 theme important 479:487 arg1 role 489:492 an important role 476:492 an important role 476:492 Galectin-7 (Gal-7) has been reported to play an important role during skin wound healing. 28526214 4 64 theme diabetic 674:681 arg1 condition 683:691 diabetic condition 674:691 diabetic condition 674:691 Previously, we had demonstrated that high glucose environment alters physiologic functions of keratinocytes and contributes to impaired wound healing in diabetic condition. 28526214 0 65 theme galectin-7 82:91 arg1 expression 93:102 galectin-7 expression 82:102 galectin-7 expression in keratinocytes 82:119 High-glucose environment induced intracellular O-GlcNAc glycosylation and reduced galectin-7 expression in keratinocytes: Implications on impaired diabetic wound healing. 28526214 1 66 with prevalence 249:258 arg1 complications 289:301 various complications 281:301 various complications 281:301 BACKGROUND Diabetes is an important global health issue due to its increasing prevalence and association with various complications. 24138592 12 0 theme differentiated 2031:2044 arg1 types 2073:2077 differentiated, but not undifferentiated, types 2031:2077 differentiated, but not undifferentiated, types of gastric adenocarcinoma 2031:2103 These results together indicate that loss of αGlcNAc in MUC6-positive cancer cells is associated with progression and poor prognosis in differentiated, but not undifferentiated, types of gastric adenocarcinoma. 24138592 11 1 theme clinicopathologic 1867:1883 arg1 variable 1885:1892 any clinicopathologic variable 1863:1892 any clinicopathologic variable 1863:1892 In undifferentiated-type adenocarcinoma, we observed no significant correlation between mucin phenotypic marker expression, including MUC6, and any clinicopathologic variable. 24138592 2 2 theme A4gnt-deficient 376:390 arg1 mice 392:395 A4gnt-deficient mice 376:395 A4gnt-deficient mice 376:395 Previously, we generated A4gnt-deficient mice, which totally lack αGlcNAc, and showed that αGlcNAc functions as a tumor suppressor for gastric cancer. 24138592 1 3 contain having 247:252 arg2 residues 305:312 terminal α1,4-linked N-acetylglucosamine (αGlcNAc) residues 254:312 terminal α1,4-linked N-acetylglucosamine (αGlcNAc) residues largely attached to a MUC6 scaffold 254:348 Gastric gland mucin secreted from the lower portion of the gastric mucosa contains unique O-linked oligosaccharides having terminal α1,4-linked N-acetylglucosamine (αGlcNAc) residues largely attached to a MUC6 scaffold. 24138592 1 3 contain having 247:252 arg1 oligosaccharides 230:245 unique O-linked oligosaccharides 214:245 unique O-linked oligosaccharides having terminal α1,4-linked N-acetylglucosamine (αGlcNAc) residues largely attached to a MUC6 scaffold 214:348 Gastric gland mucin secreted from the lower portion of the gastric mucosa contains unique O-linked oligosaccharides having terminal α1,4-linked N-acetylglucosamine (αGlcNAc) residues largely attached to a MUC6 scaffold. 24138592 11 4 theme undifferentiated-type 1722:1742 arg1 adenocarcinoma 1744:1757 undifferentiated-type adenocarcinoma 1722:1757 undifferentiated-type adenocarcinoma 1722:1757 In undifferentiated-type adenocarcinoma, we observed no significant correlation between mucin phenotypic marker expression, including MUC6, and any clinicopathologic variable. 24138592 3 5 theme gastric 572:578 arg1 carcinomas 580:589 gastric carcinomas 572:589 gastric carcinomas 572:589 Here, to determine the clinicopathological significance of αGlcNAc in gastric carcinomas, we examined immunohistochemical expression of αGlcNAc and mucin phenotypic markers including MUC5AC, MUC6, MUC2, and CD10 in 214 gastric adenocarcinomas and compared those expression patterns with clinicopathological parameters and cancer-specific survival. 24138592 12 6 from progression 1997:2007 arg1 types 2073:2077 differentiated, but not undifferentiated, types 2031:2077 differentiated, but not undifferentiated, types of gastric adenocarcinoma 2031:2103 These results together indicate that loss of αGlcNAc in MUC6-positive cancer cells is associated with progression and poor prognosis in differentiated, but not undifferentiated, types of gastric adenocarcinoma. 24138592 8 7 theme αGlcNAc 1363:1369 arg1 loss 1371:1374 αGlcNAc loss 1363:1374 αGlcNAc loss 1363:1374 By contrast, no significant correlation between αGlcNAc loss and any clinicopathologic variable was observed in undifferentiated-type adenocarcinoma. 24138592 11 8 theme significant 1775:1785 arg1 correlation 1787:1797 no significant correlation 1772:1797 no significant correlation 1772:1797 In undifferentiated-type adenocarcinoma, we observed no significant correlation between mucin phenotypic marker expression, including MUC6, and any clinicopathologic variable. 24138592 1 9 attach attached 322:329 arg2 residues 305:312 terminal α1,4-linked N-acetylglucosamine (αGlcNAc) residues 254:312 terminal α1,4-linked N-acetylglucosamine (αGlcNAc) residues largely attached to a MUC6 scaffold 254:348 Gastric gland mucin secreted from the lower portion of the gastric mucosa contains unique O-linked oligosaccharides having terminal α1,4-linked N-acetylglucosamine (αGlcNAc) residues largely attached to a MUC6 scaffold. 24138592 1 9 attach attached 322:329 arg1 scaffold 341:348 a MUC6 scaffold 334:348 a MUC6 scaffold 334:348 Gastric gland mucin secreted from the lower portion of the gastric mucosa contains unique O-linked oligosaccharides having terminal α1,4-linked N-acetylglucosamine (αGlcNAc) residues largely attached to a MUC6 scaffold. 24138592 12 10 theme cancer 1965:1970 arg1 cells 1972:1976 MUC6-positive cancer cells 1951:1976 MUC6-positive cancer cells 1951:1976 These results together indicate that loss of αGlcNAc in MUC6-positive cancer cells is associated with progression and poor prognosis in differentiated, but not undifferentiated, types of gastric adenocarcinoma. 24138592 1 11 theme gastric 190:196 arg1 mucosa 198:203 the gastric mucosa 186:203 the gastric mucosa 186:203 Gastric gland mucin secreted from the lower portion of the gastric mucosa contains unique O-linked oligosaccharides having terminal α1,4-linked N-acetylglucosamine (αGlcNAc) residues largely attached to a MUC6 scaffold. 24138592 8 12 theme clinicopathologic 1384:1400 arg1 variable 1402:1409 any clinicopathologic variable 1380:1409 any clinicopathologic variable 1380:1409 By contrast, no significant correlation between αGlcNAc loss and any clinicopathologic variable was observed in undifferentiated-type adenocarcinoma. 24138592 3 13 theme expression 764:773 arg1 patterns 775:782 those expression patterns 758:782 those expression patterns with clinicopathological parameters and cancer-specific survival 758:847 Here, to determine the clinicopathological significance of αGlcNAc in gastric carcinomas, we examined immunohistochemical expression of αGlcNAc and mucin phenotypic markers including MUC5AC, MUC6, MUC2, and CD10 in 214 gastric adenocarcinomas and compared those expression patterns with clinicopathological parameters and cancer-specific survival. 24138592 3 14 theme cancer-specific 824:838 arg1 survival 840:847 cancer-specific survival 824:847 cancer-specific survival 824:847 Here, to determine the clinicopathological significance of αGlcNAc in gastric carcinomas, we examined immunohistochemical expression of αGlcNAc and mucin phenotypic markers including MUC5AC, MUC6, MUC2, and CD10 in 214 gastric adenocarcinomas and compared those expression patterns with clinicopathological parameters and cancer-specific survival. 24138592 3 15 theme αGlcNAc 638:644 arg1 MUC2 699:702 MUC2 699:702 MUC2 699:702 Here, to determine the clinicopathological significance of αGlcNAc in gastric carcinomas, we examined immunohistochemical expression of αGlcNAc and mucin phenotypic markers including MUC5AC, MUC6, MUC2, and CD10 in 214 gastric adenocarcinomas and compared those expression patterns with clinicopathological parameters and cancer-specific survival. 24138592 3 15 theme αGlcNAc 638:644 arg1 CD10 709:712 CD10 709:712 CD10 709:712 Here, to determine the clinicopathological significance of αGlcNAc in gastric carcinomas, we examined immunohistochemical expression of αGlcNAc and mucin phenotypic markers including MUC5AC, MUC6, MUC2, and CD10 in 214 gastric adenocarcinomas and compared those expression patterns with clinicopathological parameters and cancer-specific survival. 24138592 3 15 theme αGlcNAc 638:644 arg1 MUC6 693:696 MUC6 693:696 MUC6 693:696 Here, to determine the clinicopathological significance of αGlcNAc in gastric carcinomas, we examined immunohistochemical expression of αGlcNAc and mucin phenotypic markers including MUC5AC, MUC6, MUC2, and CD10 in 214 gastric adenocarcinomas and compared those expression patterns with clinicopathological parameters and cancer-specific survival. 24138592 3 15 theme αGlcNAc 638:644 arg1 MUC5AC 685:690 MUC5AC 685:690 MUC5AC 685:690 Here, to determine the clinicopathological significance of αGlcNAc in gastric carcinomas, we examined immunohistochemical expression of αGlcNAc and mucin phenotypic markers including MUC5AC, MUC6, MUC2, and CD10 in 214 gastric adenocarcinomas and compared those expression patterns with clinicopathological parameters and cancer-specific survival. 24138592 3 15 theme αGlcNAc 638:644 arg1 markers 667:673 αGlcNAc and mucin phenotypic markers 638:673 αGlcNAc and mucin phenotypic markers including MUC5AC, MUC6, MUC2, and CD10 638:712 Here, to determine the clinicopathological significance of αGlcNAc in gastric carcinomas, we examined immunohistochemical expression of αGlcNAc and mucin phenotypic markers including MUC5AC, MUC6, MUC2, and CD10 in 214 gastric adenocarcinomas and compared those expression patterns with clinicopathological parameters and cancer-specific survival. 24138592 1 16 theme O-linked 221:228 arg1 oligosaccharides 230:245 unique O-linked oligosaccharides 214:245 unique O-linked oligosaccharides having terminal α1,4-linked N-acetylglucosamine (αGlcNAc) residues largely attached to a MUC6 scaffold 214:348 Gastric gland mucin secreted from the lower portion of the gastric mucosa contains unique O-linked oligosaccharides having terminal α1,4-linked N-acetylglucosamine (αGlcNAc) residues largely attached to a MUC6 scaffold. 24138592 1 17 theme Gastric 131:137 arg1 mucin 145:149 Gastric gland mucin 131:149 Gastric gland mucin secreted from the lower portion of the gastric mucosa 131:203 Gastric gland mucin secreted from the lower portion of the gastric mucosa contains unique O-linked oligosaccharides having terminal α1,4-linked N-acetylglucosamine (αGlcNAc) residues largely attached to a MUC6 scaffold. 24138592 12 18 theme αGlcNAc 1940:1946 arg1 loss 1932:1935 loss 1932:1935 loss of αGlcNAc in MUC6-positive cancer cells 1932:1976 These results together indicate that loss of αGlcNAc in MUC6-positive cancer cells is associated with progression and poor prognosis in differentiated, but not undifferentiated, types of gastric adenocarcinoma. 24138592 12 19 from loss 1932:1935 arg1 cells 1972:1976 MUC6-positive cancer cells 1951:1976 MUC6-positive cancer cells 1951:1976 These results together indicate that loss of αGlcNAc in MUC6-positive cancer cells is associated with progression and poor prognosis in differentiated, but not undifferentiated, types of gastric adenocarcinoma. 24138592 3 20 theme markers 667:673 arg1 expression 624:633 immunohistochemical expression 604:633 immunohistochemical expression of αGlcNAc and mucin phenotypic markers including MUC5AC, MUC6, MUC2, and CD10 in 214 gastric adenocarcinomas 604:743 Here, to determine the clinicopathological significance of αGlcNAc in gastric carcinomas, we examined immunohistochemical expression of αGlcNAc and mucin phenotypic markers including MUC5AC, MUC6, MUC2, and CD10 in 214 gastric adenocarcinomas and compared those expression patterns with clinicopathological parameters and cancer-specific survival. 24138592 12 21 theme MUC6-positive 1951:1963 arg1 cells 1972:1976 MUC6-positive cancer cells 1951:1976 MUC6-positive cancer cells 1951:1976 These results together indicate that loss of αGlcNAc in MUC6-positive cancer cells is associated with progression and poor prognosis in differentiated, but not undifferentiated, types of gastric adenocarcinoma. 24138592 3 22 theme mucin 650:654 arg1 MUC2 699:702 MUC2 699:702 MUC2 699:702 Here, to determine the clinicopathological significance of αGlcNAc in gastric carcinomas, we examined immunohistochemical expression of αGlcNAc and mucin phenotypic markers including MUC5AC, MUC6, MUC2, and CD10 in 214 gastric adenocarcinomas and compared those expression patterns with clinicopathological parameters and cancer-specific survival. 24138592 3 22 theme mucin 650:654 arg1 CD10 709:712 CD10 709:712 CD10 709:712 Here, to determine the clinicopathological significance of αGlcNAc in gastric carcinomas, we examined immunohistochemical expression of αGlcNAc and mucin phenotypic markers including MUC5AC, MUC6, MUC2, and CD10 in 214 gastric adenocarcinomas and compared those expression patterns with clinicopathological parameters and cancer-specific survival. 24138592 3 22 theme mucin 650:654 arg1 MUC6 693:696 MUC6 693:696 MUC6 693:696 Here, to determine the clinicopathological significance of αGlcNAc in gastric carcinomas, we examined immunohistochemical expression of αGlcNAc and mucin phenotypic markers including MUC5AC, MUC6, MUC2, and CD10 in 214 gastric adenocarcinomas and compared those expression patterns with clinicopathological parameters and cancer-specific survival. 24138592 3 22 theme mucin 650:654 arg1 MUC5AC 685:690 MUC5AC 685:690 MUC5AC 685:690 Here, to determine the clinicopathological significance of αGlcNAc in gastric carcinomas, we examined immunohistochemical expression of αGlcNAc and mucin phenotypic markers including MUC5AC, MUC6, MUC2, and CD10 in 214 gastric adenocarcinomas and compared those expression patterns with clinicopathological parameters and cancer-specific survival. 24138592 3 22 theme mucin 650:654 arg1 markers 667:673 αGlcNAc and mucin phenotypic markers 638:673 αGlcNAc and mucin phenotypic markers including MUC5AC, MUC6, MUC2, and CD10 638:712 Here, to determine the clinicopathological significance of αGlcNAc in gastric carcinomas, we examined immunohistochemical expression of αGlcNAc and mucin phenotypic markers including MUC5AC, MUC6, MUC2, and CD10 in 214 gastric adenocarcinomas and compared those expression patterns with clinicopathological parameters and cancer-specific survival. 24138592 9 23 from variables 1551:1559 arg1 adenocarcinoma 1584:1597 differentiated-type adenocarcinoma 1564:1597 differentiated-type adenocarcinoma 1564:1597 Expression of MUC6 was also significantly correlated with several clinicopathological variables in differentiated-type adenocarcinoma. 24138592 1 24 theme lower 169:173 arg1 portion 175:181 the lower portion 165:181 the lower portion of the gastric mucosa 165:203 Gastric gland mucin secreted from the lower portion of the gastric mucosa contains unique O-linked oligosaccharides having terminal α1,4-linked N-acetylglucosamine (αGlcNAc) residues largely attached to a MUC6 scaffold. 24138592 0 25 theme adenocarcinoma 100:113 arg1 progression 65:75 progression 65:75 progression of differentiated-type adenocarcinoma of the stomach 65:128 Loss of gastric gland mucin-specific O-glycan is associated with progression of differentiated-type adenocarcinoma of the stomach. 24138592 6 26 theme αGlcNAc 1055:1061 arg1 Loss 1047:1050 Loss 1047:1050 Loss of αGlcNAc 1047:1061 Loss of αGlcNAc was significantly correlated with depth of invasion, stage, and venous invasion by differentiated-type adenocarcinoma. 24138592 0 27 theme O-glycan 37:44 arg1 Loss 0:3 Loss 0:3 Loss of gastric gland mucin-specific O-glycan 0:44 Loss of gastric gland mucin-specific O-glycan is associated with progression of differentiated-type adenocarcinoma of the stomach. 24138592 2 28 theme tumor 465:469 arg1 suppressor 471:480 a tumor suppressor 463:480 a tumor suppressor for gastric cancer 463:499 Previously, we generated A4gnt-deficient mice, which totally lack αGlcNAc, and showed that αGlcNAc functions as a tumor suppressor for gastric cancer. 24138592 2 28 theme tumor 465:469 arg1 αGlcNAc 442:448 αGlcNAc 442:448 αGlcNAc 442:448 Previously, we generated A4gnt-deficient mice, which totally lack αGlcNAc, and showed that αGlcNAc functions as a tumor suppressor for gastric cancer. 24138592 7 29 theme differentiated-type 1279:1297 arg1 adenocarcinoma 1299:1312 MUC6-positive differentiated-type adenocarcinoma 1265:1312 MUC6-positive differentiated-type adenocarcinoma 1265:1312 Loss of αGlcNAc was also significantly associated with poorer patient prognosis in MUC6-positive differentiated-type adenocarcinoma. 24138592 6 30 theme venous 1127:1132 arg1 invasion 1134:1141 venous invasion 1127:1141 venous invasion 1127:1141 Loss of αGlcNAc was significantly correlated with depth of invasion, stage, and venous invasion by differentiated-type adenocarcinoma. 24138592 3 31 from expression 624:633 arg1 adenocarcinomas 729:743 214 gastric adenocarcinomas 717:743 214 gastric adenocarcinomas 717:743 Here, to determine the clinicopathological significance of αGlcNAc in gastric carcinomas, we examined immunohistochemical expression of αGlcNAc and mucin phenotypic markers including MUC5AC, MUC6, MUC2, and CD10 in 214 gastric adenocarcinomas and compared those expression patterns with clinicopathological parameters and cancer-specific survival. 24138592 0 32 theme gastric 8:14 arg1 O-glycan 37:44 gastric gland mucin-specific O-glycan 8:44 gastric gland mucin-specific O-glycan 8:44 Loss of gastric gland mucin-specific O-glycan is associated with progression of differentiated-type adenocarcinoma of the stomach. 24138592 5 33 theme αGlcNAc 1027:1033 arg1 expression 1035:1044 αGlcNAc expression 1027:1044 αGlcNAc expression 1027:1044 Thirty-three (61.1%) of 54 differentiated-type gastric adenocarcinomas exhibiting MUC6 in cancer cells lacked αGlcNAc expression. 24138592 7 34 theme patient 1244:1250 arg1 prognosis 1252:1260 poorer patient prognosis 1237:1260 poorer patient prognosis in MUC6-positive differentiated-type adenocarcinoma 1237:1312 Loss of αGlcNAc was also significantly associated with poorer patient prognosis in MUC6-positive differentiated-type adenocarcinoma. 24138592 0 35 theme mucin-specific 22:35 arg1 O-glycan 37:44 gastric gland mucin-specific O-glycan 8:44 gastric gland mucin-specific O-glycan 8:44 Loss of gastric gland mucin-specific O-glycan is associated with progression of differentiated-type adenocarcinoma of the stomach. 24138592 4 36 theme MUC6-positive 884:896 arg1 carcinoma 906:914 MUC6-positive gastric carcinoma 884:914 MUC6-positive gastric carcinoma 884:914 The αGlcNAc loss was evaluated in MUC6-positive gastric carcinoma. 24138592 11 37 theme marker 1824:1829 arg1 expression 1831:1840 mucin phenotypic marker expression 1807:1840 mucin phenotypic marker expression 1807:1840 In undifferentiated-type adenocarcinoma, we observed no significant correlation between mucin phenotypic marker expression, including MUC6, and any clinicopathologic variable. 24138592 9 38 theme clinicopathological 1531:1549 arg1 variables 1551:1559 several clinicopathological variables 1523:1559 several clinicopathological variables in differentiated-type adenocarcinoma 1523:1597 Expression of MUC6 was also significantly correlated with several clinicopathological variables in differentiated-type adenocarcinoma. 24138592 11 39 theme mucin 1807:1811 arg1 expression 1831:1840 mucin phenotypic marker expression 1807:1840 mucin phenotypic marker expression 1807:1840 In undifferentiated-type adenocarcinoma, we observed no significant correlation between mucin phenotypic marker expression, including MUC6, and any clinicopathologic variable. 24138592 3 40 theme αGlcNAc 561:567 arg1 significance 545:556 the clinicopathological significance 521:556 the clinicopathological significance of αGlcNAc in gastric carcinomas 521:589 Here, to determine the clinicopathological significance of αGlcNAc in gastric carcinomas, we examined immunohistochemical expression of αGlcNAc and mucin phenotypic markers including MUC5AC, MUC6, MUC2, and CD10 in 214 gastric adenocarcinomas and compared those expression patterns with clinicopathological parameters and cancer-specific survival. 24138592 3 41 theme clinicopathological 525:543 arg1 significance 545:556 the clinicopathological significance 521:556 the clinicopathological significance of αGlcNAc in gastric carcinomas 521:589 Here, to determine the clinicopathological significance of αGlcNAc in gastric carcinomas, we examined immunohistochemical expression of αGlcNAc and mucin phenotypic markers including MUC5AC, MUC6, MUC2, and CD10 in 214 gastric adenocarcinomas and compared those expression patterns with clinicopathological parameters and cancer-specific survival. 24138592 1 42 theme terminal 254:261 arg1 residues 305:312 terminal α1,4-linked N-acetylglucosamine (αGlcNAc) residues 254:312 terminal α1,4-linked N-acetylglucosamine (αGlcNAc) residues largely attached to a MUC6 scaffold 254:348 Gastric gland mucin secreted from the lower portion of the gastric mucosa contains unique O-linked oligosaccharides having terminal α1,4-linked N-acetylglucosamine (αGlcNAc) residues largely attached to a MUC6 scaffold. 24138592 1 43 theme MUC6 336:339 arg1 scaffold 341:348 a MUC6 scaffold 334:348 a MUC6 scaffold 334:348 Gastric gland mucin secreted from the lower portion of the gastric mucosa contains unique O-linked oligosaccharides having terminal α1,4-linked N-acetylglucosamine (αGlcNAc) residues largely attached to a MUC6 scaffold. 24138592 3 44 theme gastric 721:727 arg1 adenocarcinomas 729:743 214 gastric adenocarcinomas 717:743 214 gastric adenocarcinomas 717:743 Here, to determine the clinicopathological significance of αGlcNAc in gastric carcinomas, we examined immunohistochemical expression of αGlcNAc and mucin phenotypic markers including MUC5AC, MUC6, MUC2, and CD10 in 214 gastric adenocarcinomas and compared those expression patterns with clinicopathological parameters and cancer-specific survival. 24138592 1 45 theme N-acetylglucosamine 275:293 arg1 residues 305:312 terminal α1,4-linked N-acetylglucosamine (αGlcNAc) residues 254:312 terminal α1,4-linked N-acetylglucosamine (αGlcNAc) residues largely attached to a MUC6 scaffold 254:348 Gastric gland mucin secreted from the lower portion of the gastric mucosa contains unique O-linked oligosaccharides having terminal α1,4-linked N-acetylglucosamine (αGlcNAc) residues largely attached to a MUC6 scaffold. 24138592 12 46 from prognosis 2018:2026 arg1 types 2073:2077 differentiated, but not undifferentiated, types 2031:2077 differentiated, but not undifferentiated, types of gastric adenocarcinoma 2031:2103 These results together indicate that loss of αGlcNAc in MUC6-positive cancer cells is associated with progression and poor prognosis in differentiated, but not undifferentiated, types of gastric adenocarcinoma. 24138592 7 47 theme αGlcNAc 1190:1196 arg1 Loss 1182:1185 Loss 1182:1185 Loss of αGlcNAc 1182:1196 Loss of αGlcNAc was also significantly associated with poorer patient prognosis in MUC6-positive differentiated-type adenocarcinoma. 24138592 1 48 theme αGlcNAc 296:302 arg1 residues 305:312 terminal α1,4-linked N-acetylglucosamine (αGlcNAc) residues 254:312 terminal α1,4-linked N-acetylglucosamine (αGlcNAc) residues largely attached to a MUC6 scaffold 254:348 Gastric gland mucin secreted from the lower portion of the gastric mucosa contains unique O-linked oligosaccharides having terminal α1,4-linked N-acetylglucosamine (αGlcNAc) residues largely attached to a MUC6 scaffold. 24138592 12 49 theme poor 2013:2016 arg1 prognosis 2018:2026 poor prognosis 2013:2026 poor prognosis 2013:2026 These results together indicate that loss of αGlcNAc in MUC6-positive cancer cells is associated with progression and poor prognosis in differentiated, but not undifferentiated, types of gastric adenocarcinoma. 24138592 3 50 from significance 545:556 arg1 carcinomas 580:589 gastric carcinomas 572:589 gastric carcinomas 572:589 Here, to determine the clinicopathological significance of αGlcNAc in gastric carcinomas, we examined immunohistochemical expression of αGlcNAc and mucin phenotypic markers including MUC5AC, MUC6, MUC2, and CD10 in 214 gastric adenocarcinomas and compared those expression patterns with clinicopathological parameters and cancer-specific survival. 24138592 4 51 theme gastric 898:904 arg1 carcinoma 906:914 MUC6-positive gastric carcinoma 884:914 MUC6-positive gastric carcinoma 884:914 The αGlcNAc loss was evaluated in MUC6-positive gastric carcinoma. 24138592 1 52 link α1,4-linked 263:273 arg1 residues 305:312 terminal α1,4-linked N-acetylglucosamine (αGlcNAc) residues 254:312 terminal α1,4-linked N-acetylglucosamine (αGlcNAc) residues largely attached to a MUC6 scaffold 254:348 Gastric gland mucin secreted from the lower portion of the gastric mucosa contains unique O-linked oligosaccharides having terminal α1,4-linked N-acetylglucosamine (αGlcNAc) residues largely attached to a MUC6 scaffold. 24138592 3 53 theme clinicopathological 789:807 arg1 parameters 809:818 clinicopathological parameters 789:818 clinicopathological parameters 789:818 Here, to determine the clinicopathological significance of αGlcNAc in gastric carcinomas, we examined immunohistochemical expression of αGlcNAc and mucin phenotypic markers including MUC5AC, MUC6, MUC2, and CD10 in 214 gastric adenocarcinomas and compared those expression patterns with clinicopathological parameters and cancer-specific survival. 24138592 1 54 theme mucosa 198:203 arg1 portion 175:181 the lower portion 165:181 the lower portion of the gastric mucosa 165:203 Gastric gland mucin secreted from the lower portion of the gastric mucosa contains unique O-linked oligosaccharides having terminal α1,4-linked N-acetylglucosamine (αGlcNAc) residues largely attached to a MUC6 scaffold. 24138592 5 55 theme gastric 964:970 arg1 adenocarcinomas 972:986 54 differentiated-type gastric adenocarcinomas 941:986 54 differentiated-type gastric adenocarcinomas exhibiting MUC6 in cancer cells 941:1018 Thirty-three (61.1%) of 54 differentiated-type gastric adenocarcinomas exhibiting MUC6 in cancer cells lacked αGlcNAc expression. 24138592 1 56 theme unique 214:219 arg1 oligosaccharides 230:245 unique O-linked oligosaccharides 214:245 unique O-linked oligosaccharides having terminal α1,4-linked N-acetylglucosamine (αGlcNAc) residues largely attached to a MUC6 scaffold 214:348 Gastric gland mucin secreted from the lower portion of the gastric mucosa contains unique O-linked oligosaccharides having terminal α1,4-linked N-acetylglucosamine (αGlcNAc) residues largely attached to a MUC6 scaffold. 24138592 3 57 theme immunohistochemical 604:622 arg1 expression 624:633 immunohistochemical expression 604:633 immunohistochemical expression of αGlcNAc and mucin phenotypic markers including MUC5AC, MUC6, MUC2, and CD10 in 214 gastric adenocarcinomas 604:743 Here, to determine the clinicopathological significance of αGlcNAc in gastric carcinomas, we examined immunohistochemical expression of αGlcNAc and mucin phenotypic markers including MUC5AC, MUC6, MUC2, and CD10 in 214 gastric adenocarcinomas and compared those expression patterns with clinicopathological parameters and cancer-specific survival. 24138592 5 58 theme adenocarcinomas 972:986 arg1 Thirty-three 917:928 Thirty-three 917:928 Thirty-three 917:928 Thirty-three (61.1%) of 54 differentiated-type gastric adenocarcinomas exhibiting MUC6 in cancer cells lacked αGlcNAc expression. 24138592 5 58 theme adenocarcinomas 972:986 arg1 % 935:935 61.1% 931:935 61.1% 931:935 Thirty-three (61.1%) of 54 differentiated-type gastric adenocarcinomas exhibiting MUC6 in cancer cells lacked αGlcNAc expression. 24138592 5 58 theme adenocarcinomas 972:986 arg1 adenocarcinomas 972:986 54 differentiated-type gastric adenocarcinomas 941:986 54 differentiated-type gastric adenocarcinomas exhibiting MUC6 in cancer cells 941:1018 Thirty-three (61.1%) of 54 differentiated-type gastric adenocarcinomas exhibiting MUC6 in cancer cells lacked αGlcNAc expression. 24138592 8 59 theme significant 1331:1341 arg1 correlation 1343:1353 no significant correlation 1328:1353 no significant correlation between αGlcNAc loss and any clinicopathologic variable 1328:1409 By contrast, no significant correlation between αGlcNAc loss and any clinicopathologic variable was observed in undifferentiated-type adenocarcinoma. 24138592 3 60 theme phenotypic 656:665 arg1 MUC2 699:702 MUC2 699:702 MUC2 699:702 Here, to determine the clinicopathological significance of αGlcNAc in gastric carcinomas, we examined immunohistochemical expression of αGlcNAc and mucin phenotypic markers including MUC5AC, MUC6, MUC2, and CD10 in 214 gastric adenocarcinomas and compared those expression patterns with clinicopathological parameters and cancer-specific survival. 24138592 3 60 theme phenotypic 656:665 arg1 CD10 709:712 CD10 709:712 CD10 709:712 Here, to determine the clinicopathological significance of αGlcNAc in gastric carcinomas, we examined immunohistochemical expression of αGlcNAc and mucin phenotypic markers including MUC5AC, MUC6, MUC2, and CD10 in 214 gastric adenocarcinomas and compared those expression patterns with clinicopathological parameters and cancer-specific survival. 24138592 3 60 theme phenotypic 656:665 arg1 MUC6 693:696 MUC6 693:696 MUC6 693:696 Here, to determine the clinicopathological significance of αGlcNAc in gastric carcinomas, we examined immunohistochemical expression of αGlcNAc and mucin phenotypic markers including MUC5AC, MUC6, MUC2, and CD10 in 214 gastric adenocarcinomas and compared those expression patterns with clinicopathological parameters and cancer-specific survival. 24138592 3 60 theme phenotypic 656:665 arg1 MUC5AC 685:690 MUC5AC 685:690 MUC5AC 685:690 Here, to determine the clinicopathological significance of αGlcNAc in gastric carcinomas, we examined immunohistochemical expression of αGlcNAc and mucin phenotypic markers including MUC5AC, MUC6, MUC2, and CD10 in 214 gastric adenocarcinomas and compared those expression patterns with clinicopathological parameters and cancer-specific survival. 24138592 3 60 theme phenotypic 656:665 arg1 markers 667:673 αGlcNAc and mucin phenotypic markers 638:673 αGlcNAc and mucin phenotypic markers including MUC5AC, MUC6, MUC2, and CD10 638:712 Here, to determine the clinicopathological significance of αGlcNAc in gastric carcinomas, we examined immunohistochemical expression of αGlcNAc and mucin phenotypic markers including MUC5AC, MUC6, MUC2, and CD10 in 214 gastric adenocarcinomas and compared those expression patterns with clinicopathological parameters and cancer-specific survival. 24138592 1 61 theme gland 139:143 arg1 mucin 145:149 Gastric gland mucin 131:149 Gastric gland mucin secreted from the lower portion of the gastric mucosa 131:203 Gastric gland mucin secreted from the lower portion of the gastric mucosa contains unique O-linked oligosaccharides having terminal α1,4-linked N-acetylglucosamine (αGlcNAc) residues largely attached to a MUC6 scaffold. 24138592 10 62 with correlation 1664:1674 arg1 survival 1697:1704 cancer-specific survival 1681:1704 cancer-specific survival in patients 1681:1716 However, unlike the case with αGlcNAc, its expression showed no correlation with cancer-specific survival in patients. 24138592 6 63 theme invasion 1106:1113 arg1 depth 1097:1101 depth 1097:1101 depth of invasion, stage, and venous invasion by differentiated-type adenocarcinoma 1097:1179 Loss of αGlcNAc was significantly correlated with depth of invasion, stage, and venous invasion by differentiated-type adenocarcinoma. 24138592 8 64 theme undifferentiated-type 1427:1447 arg1 adenocarcinoma 1449:1462 undifferentiated-type adenocarcinoma 1427:1462 undifferentiated-type adenocarcinoma 1427:1462 By contrast, no significant correlation between αGlcNAc loss and any clinicopathologic variable was observed in undifferentiated-type adenocarcinoma. 24138592 10 65 from survival 1697:1704 arg1 patients 1709:1716 patients 1709:1716 patients 1709:1716 However, unlike the case with αGlcNAc, its expression showed no correlation with cancer-specific survival in patients. 24138592 0 66 theme differentiated-type 80:98 arg1 adenocarcinoma 100:113 differentiated-type adenocarcinoma 80:113 differentiated-type adenocarcinoma of the stomach 80:128 Loss of gastric gland mucin-specific O-glycan is associated with progression of differentiated-type adenocarcinoma of the stomach. 24138592 12 67 theme gastric 2082:2088 arg1 adenocarcinoma 2090:2103 gastric adenocarcinoma 2082:2103 gastric adenocarcinoma 2082:2103 These results together indicate that loss of αGlcNAc in MUC6-positive cancer cells is associated with progression and poor prognosis in differentiated, but not undifferentiated, types of gastric adenocarcinoma. 24138592 5 68 theme differentiated-type 944:962 arg1 adenocarcinomas 972:986 54 differentiated-type gastric adenocarcinomas 941:986 54 differentiated-type gastric adenocarcinomas exhibiting MUC6 in cancer cells 941:1018 Thirty-three (61.1%) of 54 differentiated-type gastric adenocarcinomas exhibiting MUC6 in cancer cells lacked αGlcNAc expression. 24138592 1 69 link O-linked 221:228 arg1 oligosaccharides 230:245 unique O-linked oligosaccharides 214:245 unique O-linked oligosaccharides having terminal α1,4-linked N-acetylglucosamine (αGlcNAc) residues largely attached to a MUC6 scaffold 214:348 Gastric gland mucin secreted from the lower portion of the gastric mucosa contains unique O-linked oligosaccharides having terminal α1,4-linked N-acetylglucosamine (αGlcNAc) residues largely attached to a MUC6 scaffold. 24138592 7 70 from prognosis 1252:1260 arg1 adenocarcinoma 1299:1312 MUC6-positive differentiated-type adenocarcinoma 1265:1312 MUC6-positive differentiated-type adenocarcinoma 1265:1312 Loss of αGlcNAc was also significantly associated with poorer patient prognosis in MUC6-positive differentiated-type adenocarcinoma. 24138592 0 71 theme stomach 122:128 arg1 adenocarcinoma 100:113 differentiated-type adenocarcinoma 80:113 differentiated-type adenocarcinoma of the stomach 80:128 Loss of gastric gland mucin-specific O-glycan is associated with progression of differentiated-type adenocarcinoma of the stomach. 24138592 10 72 with case 1620:1623 arg1 αGlcNAc 1630:1636 αGlcNAc 1630:1636 αGlcNAc 1630:1636 However, unlike the case with αGlcNAc, its expression showed no correlation with cancer-specific survival in patients. 24138592 6 73 theme differentiated-type 1146:1164 arg1 adenocarcinoma 1166:1179 differentiated-type adenocarcinoma 1146:1179 differentiated-type adenocarcinoma 1146:1179 Loss of αGlcNAc was significantly correlated with depth of invasion, stage, and venous invasion by differentiated-type adenocarcinoma. 24138592 7 74 theme MUC6-positive 1265:1277 arg1 adenocarcinoma 1299:1312 MUC6-positive differentiated-type adenocarcinoma 1265:1312 MUC6-positive differentiated-type adenocarcinoma 1265:1312 Loss of αGlcNAc was also significantly associated with poorer patient prognosis in MUC6-positive differentiated-type adenocarcinoma. 24138592 9 75 theme MUC6 1479:1482 arg1 Expression 1465:1474 Expression 1465:1474 Expression of MUC6 1465:1482 Expression of MUC6 was also significantly correlated with several clinicopathological variables in differentiated-type adenocarcinoma. 24138592 3 76 with patterns 775:782 arg1 parameters 809:818 clinicopathological parameters 789:818 clinicopathological parameters 789:818 Here, to determine the clinicopathological significance of αGlcNAc in gastric carcinomas, we examined immunohistochemical expression of αGlcNAc and mucin phenotypic markers including MUC5AC, MUC6, MUC2, and CD10 in 214 gastric adenocarcinomas and compared those expression patterns with clinicopathological parameters and cancer-specific survival. 24138592 3 76 with patterns 775:782 arg1 survival 840:847 cancer-specific survival 824:847 cancer-specific survival 824:847 Here, to determine the clinicopathological significance of αGlcNAc in gastric carcinomas, we examined immunohistochemical expression of αGlcNAc and mucin phenotypic markers including MUC5AC, MUC6, MUC2, and CD10 in 214 gastric adenocarcinomas and compared those expression patterns with clinicopathological parameters and cancer-specific survival. 24138592 5 77 theme cancer 1007:1012 arg1 cells 1014:1018 cancer cells 1007:1018 cancer cells 1007:1018 Thirty-three (61.1%) of 54 differentiated-type gastric adenocarcinomas exhibiting MUC6 in cancer cells lacked αGlcNAc expression. 24138592 6 78 theme invasion 1134:1141 arg1 depth 1097:1101 depth 1097:1101 depth of invasion, stage, and venous invasion by differentiated-type adenocarcinoma 1097:1179 Loss of αGlcNAc was significantly correlated with depth of invasion, stage, and venous invasion by differentiated-type adenocarcinoma. 24138592 0 79 theme gland 16:20 arg1 O-glycan 37:44 gastric gland mucin-specific O-glycan 8:44 gastric gland mucin-specific O-glycan 8:44 Loss of gastric gland mucin-specific O-glycan is associated with progression of differentiated-type adenocarcinoma of the stomach. 24138592 8 80 located observed 1415:1422 arg2 correlation 1343:1353 no significant correlation 1328:1353 no significant correlation between αGlcNAc loss and any clinicopathologic variable 1328:1409 By contrast, no significant correlation between αGlcNAc loss and any clinicopathologic variable was observed in undifferentiated-type adenocarcinoma. 24138592 8 80 located observed 1415:1422 arg1 adenocarcinoma 1449:1462 undifferentiated-type adenocarcinoma 1427:1462 undifferentiated-type adenocarcinoma 1427:1462 By contrast, no significant correlation between αGlcNAc loss and any clinicopathologic variable was observed in undifferentiated-type adenocarcinoma. 24138592 10 81 theme cancer-specific 1681:1695 arg1 survival 1697:1704 cancer-specific survival 1681:1704 cancer-specific survival in patients 1681:1716 However, unlike the case with αGlcNAc, its expression showed no correlation with cancer-specific survival in patients. 24138592 7 82 theme poorer 1237:1242 arg1 prognosis 1252:1260 poorer patient prognosis 1237:1260 poorer patient prognosis in MUC6-positive differentiated-type adenocarcinoma 1237:1312 Loss of αGlcNAc was also significantly associated with poorer patient prognosis in MUC6-positive differentiated-type adenocarcinoma. 24138592 6 83 theme stage 1116:1120 arg1 depth 1097:1101 depth 1097:1101 depth of invasion, stage, and venous invasion by differentiated-type adenocarcinoma 1097:1179 Loss of αGlcNAc was significantly correlated with depth of invasion, stage, and venous invasion by differentiated-type adenocarcinoma. 24138592 2 84 theme gastric 486:492 arg1 cancer 494:499 gastric cancer 486:499 gastric cancer 486:499 Previously, we generated A4gnt-deficient mice, which totally lack αGlcNAc, and showed that αGlcNAc functions as a tumor suppressor for gastric cancer. 24138592 11 85 theme phenotypic 1813:1822 arg1 expression 1831:1840 mucin phenotypic marker expression 1807:1840 mucin phenotypic marker expression 1807:1840 In undifferentiated-type adenocarcinoma, we observed no significant correlation between mucin phenotypic marker expression, including MUC6, and any clinicopathologic variable. 24138592 9 86 theme several 1523:1529 arg1 variables 1551:1559 several clinicopathological variables 1523:1559 several clinicopathological variables in differentiated-type adenocarcinoma 1523:1597 Expression of MUC6 was also significantly correlated with several clinicopathological variables in differentiated-type adenocarcinoma. 24138592 12 87 theme adenocarcinoma 2090:2103 arg1 types 2073:2077 differentiated, but not undifferentiated, types 2031:2077 differentiated, but not undifferentiated, types of gastric adenocarcinoma 2031:2103 These results together indicate that loss of αGlcNAc in MUC6-positive cancer cells is associated with progression and poor prognosis in differentiated, but not undifferentiated, types of gastric adenocarcinoma. 24138592 12 88 theme undifferentiated 2055:2070 arg1 types 2073:2077 differentiated, but not undifferentiated, types 2031:2077 differentiated, but not undifferentiated, types of gastric adenocarcinoma 2031:2103 These results together indicate that loss of αGlcNAc in MUC6-positive cancer cells is associated with progression and poor prognosis in differentiated, but not undifferentiated, types of gastric adenocarcinoma. 24138592 1 89 contain contains 205:212 arg2 oligosaccharides 230:245 unique O-linked oligosaccharides 214:245 unique O-linked oligosaccharides having terminal α1,4-linked N-acetylglucosamine (αGlcNAc) residues largely attached to a MUC6 scaffold 214:348 Gastric gland mucin secreted from the lower portion of the gastric mucosa contains unique O-linked oligosaccharides having terminal α1,4-linked N-acetylglucosamine (αGlcNAc) residues largely attached to a MUC6 scaffold. 24138592 1 89 contain contains 205:212 arg1 mucin 145:149 Gastric gland mucin 131:149 Gastric gland mucin secreted from the lower portion of the gastric mucosa 131:203 Gastric gland mucin secreted from the lower portion of the gastric mucosa contains unique O-linked oligosaccharides having terminal α1,4-linked N-acetylglucosamine (αGlcNAc) residues largely attached to a MUC6 scaffold. 24138592 9 90 theme differentiated-type 1564:1582 arg1 adenocarcinoma 1584:1597 differentiated-type adenocarcinoma 1564:1597 differentiated-type adenocarcinoma 1564:1597 Expression of MUC6 was also significantly correlated with several clinicopathological variables in differentiated-type adenocarcinoma. 24138592 4 91 theme αGlcNAc 854:860 arg1 loss 862:865 The αGlcNAc loss 850:865 The αGlcNAc loss 850:865 The αGlcNAc loss was evaluated in MUC6-positive gastric carcinoma. 24138592 1 92 theme α1,4-linked 263:273 arg1 residues 305:312 terminal α1,4-linked N-acetylglucosamine (αGlcNAc) residues 254:312 terminal α1,4-linked N-acetylglucosamine (αGlcNAc) residues largely attached to a MUC6 scaffold 254:348 Gastric gland mucin secreted from the lower portion of the gastric mucosa contains unique O-linked oligosaccharides having terminal α1,4-linked N-acetylglucosamine (αGlcNAc) residues largely attached to a MUC6 scaffold. 28906588 9 0 theme cell-based 1853:1862 arg1 therapy 1864:1870 clinical cell-based therapy 1844:1870 clinical cell-based therapy 1844:1870 These results could be valuable as resources and references for MSC differentiation and molecular remodeling in clinical cell-based therapy and tissue engineering studies. 28906588 7 1 theme sialic 1220:1225 arg1 MAL 1233:1235 MAL II 1233:1238 MAL II 1233:1238 In addition, cMSCs expressed more α2,3-linked sialic acid (MAL II), terminal lactosamine (RCA120 ), and α1,6 and α1,3 fucosylated oligosaccharides (PSA, LTA); oMSCs exhibited more T antigen (Jacalin), GalNAcα1,3(LFucα1,2)Galβ1,3/4GlcNAcβ1 (DBA), chitotriose (succinylated WGA), and α1,2-linked fucose (UEA I); and eMSCs showed a higher density of α2,6 sialic acids (SNA) and high mannose N-glycans (Con A). 28906588 7 1 theme sialic 1220:1225 arg1 acid 1227:1230 more α2,3-linked sialic acid 1203:1230 more α2,3-linked sialic acid (MAL II) 1203:1239 In addition, cMSCs expressed more α2,3-linked sialic acid (MAL II), terminal lactosamine (RCA120 ), and α1,6 and α1,3 fucosylated oligosaccharides (PSA, LTA); oMSCs exhibited more T antigen (Jacalin), GalNAcα1,3(LFucα1,2)Galβ1,3/4GlcNAcβ1 (DBA), chitotriose (succinylated WGA), and α1,2-linked fucose (UEA I); and eMSCs showed a higher density of α2,6 sialic acids (SNA) and high mannose N-glycans (Con A). 28906588 5 2 contain contained 934:942 arg1 surface 898:904 the MSC surface 890:904 the MSC surface of the investigated species 890:932 The lectin-binding signals indicated that the MSC surface of the investigated species contained both N- and O-linked glycan types, with N-glycosylation predominating over O-glycosylation and fucosylation being more abundant than sialylation. 28906588 5 2 contain contained 934:942 arg2 N- 949:950 N- 949:950 N- 949:950 The lectin-binding signals indicated that the MSC surface of the investigated species contained both N- and O-linked glycan types, with N-glycosylation predominating over O-glycosylation and fucosylation being more abundant than sialylation. 28906588 5 2 contain contained 934:942 arg2 types 972:976 O-linked glycan types 956:976 O-linked glycan types 956:976 The lectin-binding signals indicated that the MSC surface of the investigated species contained both N- and O-linked glycan types, with N-glycosylation predominating over O-glycosylation and fucosylation being more abundant than sialylation. 28906588 1 3 from variability 285:295 arg1 expression 337:346 species-specific cell surface marker expression 300:346 species-specific cell surface marker expression 300:346 The use of bone marrow-derived mesenchymal stem cells (MSCs) for clinical and experimental studies is increasing, but full characterization of MSCs in veterinary species is hindered by the variability in species-specific cell surface marker expression and antibody cross reactivity. 28906588 1 3 from variability 285:295 arg1 reactivity 367:376 antibody cross reactivity 352:376 antibody cross reactivity 352:376 The use of bone marrow-derived mesenchymal stem cells (MSCs) for clinical and experimental studies is increasing, but full characterization of MSCs in veterinary species is hindered by the variability in species-specific cell surface marker expression and antibody cross reactivity. 28906588 1 4 theme MSCs 239:242 arg1 characterization 219:234 full characterization 214:234 full characterization of MSCs in veterinary species 214:264 The use of bone marrow-derived mesenchymal stem cells (MSCs) for clinical and experimental studies is increasing, but full characterization of MSCs in veterinary species is hindered by the variability in species-specific cell surface marker expression and antibody cross reactivity. 28906588 7 5 theme T 1354:1354 arg1 antigen 1356:1362 more T antigen 1349:1362 more T antigen (Jacalin) 1349:1372 In addition, cMSCs expressed more α2,3-linked sialic acid (MAL II), terminal lactosamine (RCA120 ), and α1,6 and α1,3 fucosylated oligosaccharides (PSA, LTA); oMSCs exhibited more T antigen (Jacalin), GalNAcα1,3(LFucα1,2)Galβ1,3/4GlcNAcβ1 (DBA), chitotriose (succinylated WGA), and α1,2-linked fucose (UEA I); and eMSCs showed a higher density of α2,6 sialic acids (SNA) and high mannose N-glycans (Con A). 28906588 7 5 theme T 1354:1354 arg1 Jacalin 1365:1371 Jacalin 1365:1371 Jacalin 1365:1371 In addition, cMSCs expressed more α2,3-linked sialic acid (MAL II), terminal lactosamine (RCA120 ), and α1,6 and α1,3 fucosylated oligosaccharides (PSA, LTA); oMSCs exhibited more T antigen (Jacalin), GalNAcα1,3(LFucα1,2)Galβ1,3/4GlcNAcβ1 (DBA), chitotriose (succinylated WGA), and α1,2-linked fucose (UEA I); and eMSCs showed a higher density of α2,6 sialic acids (SNA) and high mannose N-glycans (Con A). 28906588 3 6 theme microarray 625:634 arg1 procedure 636:644 a cell microarray procedure 618:644 a cell microarray procedure in which MSCs were spotted on microarray slides and incubated with a panel of 14 biotinylated lectins and Cy3-conjugated streptavidin 618:778 In the present study, we analyzed the glycocalyx of canine MSCs (cMSCs), ovine MSCs (oMSCs), and equine MSCs (eMSCs) using a cell microarray procedure in which MSCs were spotted on microarray slides and incubated with a panel of 14 biotinylated lectins and Cy3-conjugated streptavidin. 28906588 6 7 theme interspecific 1126:1138 arg1 difference 1140:1149 an interspecific difference 1123:1149 an interspecific difference between these glycans 1123:1171 Relative quantification revealed an interspecific difference between these glycans. 28906588 10 8 theme Cytometry 1952:1960 arg1 Advancement 1937:1947 Advancement 1937:1947 Advancement of Cytometry 1937:1960 © 2017 International Society for Advancement of Cytometry. 28906588 8 9 theme eMSC 1717:1720 arg1 surfaces 1722:1729 eMSC surfaces 1717:1729 eMSC surfaces 1717:1729 Using cell microarray methodology, we have for the first time demonstrated differences in the glycosylation profiles of cMSC, oMSC, and eMSC surfaces. 28906588 3 10 theme canine 547:552 arg1 cMSCs 560:564 cMSCs 560:564 cMSCs 560:564 In the present study, we analyzed the glycocalyx of canine MSCs (cMSCs), ovine MSCs (oMSCs), and equine MSCs (eMSCs) using a cell microarray procedure in which MSCs were spotted on microarray slides and incubated with a panel of 14 biotinylated lectins and Cy3-conjugated streptavidin. 28906588 3 10 theme canine 547:552 arg1 MSCs 554:557 canine MSCs 547:557 canine MSCs (cMSCs) 547:565 In the present study, we analyzed the glycocalyx of canine MSCs (cMSCs), ovine MSCs (oMSCs), and equine MSCs (eMSCs) using a cell microarray procedure in which MSCs were spotted on microarray slides and incubated with a panel of 14 biotinylated lectins and Cy3-conjugated streptavidin. 28906588 7 11 gly fucosylated 1292:1302 arg1 oligosaccharides 1304:1319 α1,3 fucosylated oligosaccharides 1287:1319 α1,3 fucosylated oligosaccharides 1287:1319 In addition, cMSCs expressed more α2,3-linked sialic acid (MAL II), terminal lactosamine (RCA120 ), and α1,6 and α1,3 fucosylated oligosaccharides (PSA, LTA); oMSCs exhibited more T antigen (Jacalin), GalNAcα1,3(LFucα1,2)Galβ1,3/4GlcNAcβ1 (DBA), chitotriose (succinylated WGA), and α1,2-linked fucose (UEA I); and eMSCs showed a higher density of α2,6 sialic acids (SNA) and high mannose N-glycans (Con A). 28906588 1 12 theme cross 361:365 arg1 reactivity 367:376 antibody cross reactivity 352:376 antibody cross reactivity 352:376 The use of bone marrow-derived mesenchymal stem cells (MSCs) for clinical and experimental studies is increasing, but full characterization of MSCs in veterinary species is hindered by the variability in species-specific cell surface marker expression and antibody cross reactivity. 28906588 7 13 link α2,3-linked 1208:1218 arg1 MAL 1233:1235 MAL II 1233:1238 MAL II 1233:1238 In addition, cMSCs expressed more α2,3-linked sialic acid (MAL II), terminal lactosamine (RCA120 ), and α1,6 and α1,3 fucosylated oligosaccharides (PSA, LTA); oMSCs exhibited more T antigen (Jacalin), GalNAcα1,3(LFucα1,2)Galβ1,3/4GlcNAcβ1 (DBA), chitotriose (succinylated WGA), and α1,2-linked fucose (UEA I); and eMSCs showed a higher density of α2,6 sialic acids (SNA) and high mannose N-glycans (Con A). 28906588 7 13 link α2,3-linked 1208:1218 arg1 acid 1227:1230 more α2,3-linked sialic acid 1203:1230 more α2,3-linked sialic acid (MAL II) 1203:1239 In addition, cMSCs expressed more α2,3-linked sialic acid (MAL II), terminal lactosamine (RCA120 ), and α1,6 and α1,3 fucosylated oligosaccharides (PSA, LTA); oMSCs exhibited more T antigen (Jacalin), GalNAcα1,3(LFucα1,2)Galβ1,3/4GlcNAcβ1 (DBA), chitotriose (succinylated WGA), and α1,2-linked fucose (UEA I); and eMSCs showed a higher density of α2,6 sialic acids (SNA) and high mannose N-glycans (Con A). 28906588 5 14 link O-linked 956:963 arg1 types 972:976 O-linked glycan types 956:976 O-linked glycan types 956:976 The lectin-binding signals indicated that the MSC surface of the investigated species contained both N- and O-linked glycan types, with N-glycosylation predominating over O-glycosylation and fucosylation being more abundant than sialylation. 28906588 7 15 theme higher 1503:1508 arg1 density 1510:1516 a higher density 1501:1516 a higher density of α2,6 sialic acids (SNA) 1501:1543 In addition, cMSCs expressed more α2,3-linked sialic acid (MAL II), terminal lactosamine (RCA120 ), and α1,6 and α1,3 fucosylated oligosaccharides (PSA, LTA); oMSCs exhibited more T antigen (Jacalin), GalNAcα1,3(LFucα1,2)Galβ1,3/4GlcNAcβ1 (DBA), chitotriose (succinylated WGA), and α1,2-linked fucose (UEA I); and eMSCs showed a higher density of α2,6 sialic acids (SNA) and high mannose N-glycans (Con A). 28906588 7 15 theme higher 1503:1508 arg1 SNA 1540:1542 SNA 1540:1542 SNA 1540:1542 In addition, cMSCs expressed more α2,3-linked sialic acid (MAL II), terminal lactosamine (RCA120 ), and α1,6 and α1,3 fucosylated oligosaccharides (PSA, LTA); oMSCs exhibited more T antigen (Jacalin), GalNAcα1,3(LFucα1,2)Galβ1,3/4GlcNAcβ1 (DBA), chitotriose (succinylated WGA), and α1,2-linked fucose (UEA I); and eMSCs showed a higher density of α2,6 sialic acids (SNA) and high mannose N-glycans (Con A). 28906588 1 16 from characterization 219:234 arg1 species 258:264 veterinary species 247:264 veterinary species 247:264 The use of bone marrow-derived mesenchymal stem cells (MSCs) for clinical and experimental studies is increasing, but full characterization of MSCs in veterinary species is hindered by the variability in species-specific cell surface marker expression and antibody cross reactivity. 28906588 8 17 theme microarray 1592:1601 arg1 methodology 1603:1613 cell microarray methodology 1587:1613 cell microarray methodology 1587:1613 Using cell microarray methodology, we have for the first time demonstrated differences in the glycosylation profiles of cMSC, oMSC, and eMSC surfaces. 28906588 8 18 from differences 1656:1666 arg1 profiles 1689:1696 the glycosylation profiles 1671:1696 the glycosylation profiles of cMSC, oMSC, and eMSC surfaces 1671:1729 Using cell microarray methodology, we have for the first time demonstrated differences in the glycosylation profiles of cMSC, oMSC, and eMSC surfaces. 28906588 3 19 theme microarray 676:685 arg1 slides 687:692 microarray slides 676:692 microarray slides 676:692 In the present study, we analyzed the glycocalyx of canine MSCs (cMSCs), ovine MSCs (oMSCs), and equine MSCs (eMSCs) using a cell microarray procedure in which MSCs were spotted on microarray slides and incubated with a panel of 14 biotinylated lectins and Cy3-conjugated streptavidin. 28906588 4 20 theme microarray 828:837 arg1 scanner 839:845 a microarray scanner 826:845 a microarray scanner 826:845 The signal intensity was then detected using a microarray scanner. 28906588 9 21 theme MSC 1796:1798 arg1 differentiation 1800:1814 MSC differentiation 1796:1814 MSC differentiation 1796:1814 These results could be valuable as resources and references for MSC differentiation and molecular remodeling in clinical cell-based therapy and tissue engineering studies. 28906588 5 22 theme lectin-binding 852:865 arg1 signals 867:873 The lectin-binding signals 848:873 The lectin-binding signals 848:873 The lectin-binding signals indicated that the MSC surface of the investigated species contained both N- and O-linked glycan types, with N-glycosylation predominating over O-glycosylation and fucosylation being more abundant than sialylation. 28906588 3 23 theme Cy3-conjugated 752:765 arg1 streptavidin 767:778 Cy3-conjugated streptavidin 752:778 Cy3-conjugated streptavidin 752:778 In the present study, we analyzed the glycocalyx of canine MSCs (cMSCs), ovine MSCs (oMSCs), and equine MSCs (eMSCs) using a cell microarray procedure in which MSCs were spotted on microarray slides and incubated with a panel of 14 biotinylated lectins and Cy3-conjugated streptavidin. 28906588 7 24 theme α1,3 1287:1290 arg1 oligosaccharides 1304:1319 α1,3 fucosylated oligosaccharides 1287:1319 α1,3 fucosylated oligosaccharides 1287:1319 In addition, cMSCs expressed more α2,3-linked sialic acid (MAL II), terminal lactosamine (RCA120 ), and α1,6 and α1,3 fucosylated oligosaccharides (PSA, LTA); oMSCs exhibited more T antigen (Jacalin), GalNAcα1,3(LFucα1,2)Galβ1,3/4GlcNAcβ1 (DBA), chitotriose (succinylated WGA), and α1,2-linked fucose (UEA I); and eMSCs showed a higher density of α2,6 sialic acids (SNA) and high mannose N-glycans (Con A). 28906588 7 25 theme α2,3-linked 1208:1218 arg1 MAL 1233:1235 MAL II 1233:1238 MAL II 1233:1238 In addition, cMSCs expressed more α2,3-linked sialic acid (MAL II), terminal lactosamine (RCA120 ), and α1,6 and α1,3 fucosylated oligosaccharides (PSA, LTA); oMSCs exhibited more T antigen (Jacalin), GalNAcα1,3(LFucα1,2)Galβ1,3/4GlcNAcβ1 (DBA), chitotriose (succinylated WGA), and α1,2-linked fucose (UEA I); and eMSCs showed a higher density of α2,6 sialic acids (SNA) and high mannose N-glycans (Con A). 28906588 7 25 theme α2,3-linked 1208:1218 arg1 acid 1227:1230 more α2,3-linked sialic acid 1203:1230 more α2,3-linked sialic acid (MAL II) 1203:1239 In addition, cMSCs expressed more α2,3-linked sialic acid (MAL II), terminal lactosamine (RCA120 ), and α1,6 and α1,3 fucosylated oligosaccharides (PSA, LTA); oMSCs exhibited more T antigen (Jacalin), GalNAcα1,3(LFucα1,2)Galβ1,3/4GlcNAcβ1 (DBA), chitotriose (succinylated WGA), and α1,2-linked fucose (UEA I); and eMSCs showed a higher density of α2,6 sialic acids (SNA) and high mannose N-glycans (Con A). 28906588 3 26 theme ovine 568:572 arg1 oMSCs 580:584 oMSCs 580:584 oMSCs 580:584 In the present study, we analyzed the glycocalyx of canine MSCs (cMSCs), ovine MSCs (oMSCs), and equine MSCs (eMSCs) using a cell microarray procedure in which MSCs were spotted on microarray slides and incubated with a panel of 14 biotinylated lectins and Cy3-conjugated streptavidin. 28906588 3 26 theme ovine 568:572 arg1 MSCs 574:577 ovine MSCs 568:577 ovine MSCs (oMSCs) 568:585 In the present study, we analyzed the glycocalyx of canine MSCs (cMSCs), ovine MSCs (oMSCs), and equine MSCs (eMSCs) using a cell microarray procedure in which MSCs were spotted on microarray slides and incubated with a panel of 14 biotinylated lectins and Cy3-conjugated streptavidin. 28906588 1 27 theme mesenchymal 127:137 arg1 MSCs 151:154 MSCs 151:154 MSCs 151:154 The use of bone marrow-derived mesenchymal stem cells (MSCs) for clinical and experimental studies is increasing, but full characterization of MSCs in veterinary species is hindered by the variability in species-specific cell surface marker expression and antibody cross reactivity. 28906588 1 27 theme mesenchymal 127:137 arg1 cells 144:148 bone marrow-derived mesenchymal stem cells 107:148 bone marrow-derived mesenchymal stem cells (MSCs) 107:155 The use of bone marrow-derived mesenchymal stem cells (MSCs) for clinical and experimental studies is increasing, but full characterization of MSCs in veterinary species is hindered by the variability in species-specific cell surface marker expression and antibody cross reactivity. 28906588 2 28 from glycans 416:422 arg1 glycocalyx 431:440 the glycocalyx 427:440 the glycocalyx of MSCs 427:448 Recent studies demonstrated that the glycans in the glycocalyx of MSCs are promising candidates as cell biomarkers. 28906588 3 29 theme lectins 740:746 arg1 panel 715:719 a panel 713:719 a panel of 14 biotinylated lectins and Cy3-conjugated streptavidin 713:778 In the present study, we analyzed the glycocalyx of canine MSCs (cMSCs), ovine MSCs (oMSCs), and equine MSCs (eMSCs) using a cell microarray procedure in which MSCs were spotted on microarray slides and incubated with a panel of 14 biotinylated lectins and Cy3-conjugated streptavidin. 28906588 0 30 theme bone 52:55 arg1 cells 89:93 ovine bone marrow-derived mesenchymal stem cells 46:93 ovine bone marrow-derived mesenchymal stem cells 46:93 Surface glycan pattern of canine, equine, and ovine bone marrow-derived mesenchymal stem cells. 28906588 1 31 theme cell 317:320 arg1 expression 337:346 species-specific cell surface marker expression 300:346 species-specific cell surface marker expression 300:346 The use of bone marrow-derived mesenchymal stem cells (MSCs) for clinical and experimental studies is increasing, but full characterization of MSCs in veterinary species is hindered by the variability in species-specific cell surface marker expression and antibody cross reactivity. 28906588 1 32 theme cells 144:148 arg1 use 100:102 The use 96:102 The use of bone marrow-derived mesenchymal stem cells (MSCs) for clinical and experimental studies 96:193 The use of bone marrow-derived mesenchymal stem cells (MSCs) for clinical and experimental studies is increasing, but full characterization of MSCs in veterinary species is hindered by the variability in species-specific cell surface marker expression and antibody cross reactivity. 28906588 7 33 theme mannose 1554:1560 arg1 N-glycans 1562:1570 high mannose N-glycans 1549:1570 high mannose N-glycans (Con A) 1549:1578 In addition, cMSCs expressed more α2,3-linked sialic acid (MAL II), terminal lactosamine (RCA120 ), and α1,6 and α1,3 fucosylated oligosaccharides (PSA, LTA); oMSCs exhibited more T antigen (Jacalin), GalNAcα1,3(LFucα1,2)Galβ1,3/4GlcNAcβ1 (DBA), chitotriose (succinylated WGA), and α1,2-linked fucose (UEA I); and eMSCs showed a higher density of α2,6 sialic acids (SNA) and high mannose N-glycans (Con A). 28906588 7 33 theme mannose 1554:1560 arg1 A 1577:1577 Con A 1573:1577 Con A 1573:1577 In addition, cMSCs expressed more α2,3-linked sialic acid (MAL II), terminal lactosamine (RCA120 ), and α1,6 and α1,3 fucosylated oligosaccharides (PSA, LTA); oMSCs exhibited more T antigen (Jacalin), GalNAcα1,3(LFucα1,2)Galβ1,3/4GlcNAcβ1 (DBA), chitotriose (succinylated WGA), and α1,2-linked fucose (UEA I); and eMSCs showed a higher density of α2,6 sialic acids (SNA) and high mannose N-glycans (Con A). 28906588 9 34 theme clinical 1844:1851 arg1 therapy 1864:1870 clinical cell-based therapy 1844:1870 clinical cell-based therapy 1844:1870 These results could be valuable as resources and references for MSC differentiation and molecular remodeling in clinical cell-based therapy and tissue engineering studies. 28906588 0 35 theme mesenchymal 72:82 arg1 cells 89:93 ovine bone marrow-derived mesenchymal stem cells 46:93 ovine bone marrow-derived mesenchymal stem cells 46:93 Surface glycan pattern of canine, equine, and ovine bone marrow-derived mesenchymal stem cells. 28906588 1 36 theme marker 330:335 arg1 expression 337:346 species-specific cell surface marker expression 300:346 species-specific cell surface marker expression 300:346 The use of bone marrow-derived mesenchymal stem cells (MSCs) for clinical and experimental studies is increasing, but full characterization of MSCs in veterinary species is hindered by the variability in species-specific cell surface marker expression and antibody cross reactivity. 28906588 2 37 theme Recent 379:384 arg1 studies 386:392 Recent studies 379:392 Recent studies 379:392 Recent studies demonstrated that the glycans in the glycocalyx of MSCs are promising candidates as cell biomarkers. 28906588 0 38 theme cells 89:93 arg1 pattern 15:21 Surface glycan pattern 0:21 Surface glycan pattern of canine, equine, and ovine bone marrow-derived mesenchymal stem cells 0:93 Surface glycan pattern of canine, equine, and ovine bone marrow-derived mesenchymal stem cells. 28906588 9 39 from remodeling 1830:1839 arg1 therapy 1864:1870 clinical cell-based therapy 1844:1870 clinical cell-based therapy 1844:1870 These results could be valuable as resources and references for MSC differentiation and molecular remodeling in clinical cell-based therapy and tissue engineering studies. 28906588 9 39 from remodeling 1830:1839 arg1 studies 1895:1901 tissue engineering studies 1876:1901 tissue engineering studies 1876:1901 These results could be valuable as resources and references for MSC differentiation and molecular remodeling in clinical cell-based therapy and tissue engineering studies. 28906588 9 40 theme tissue 1876:1881 arg1 studies 1895:1901 tissue engineering studies 1876:1901 tissue engineering studies 1876:1901 These results could be valuable as resources and references for MSC differentiation and molecular remodeling in clinical cell-based therapy and tissue engineering studies. 28906588 0 41 theme Surface 0:6 arg1 pattern 15:21 Surface glycan pattern 0:21 Surface glycan pattern of canine, equine, and ovine bone marrow-derived mesenchymal stem cells 0:93 Surface glycan pattern of canine, equine, and ovine bone marrow-derived mesenchymal stem cells. 28906588 7 42 theme acids 1533:1537 arg1 SNA 1540:1542 SNA 1540:1542 SNA 1540:1542 In addition, cMSCs expressed more α2,3-linked sialic acid (MAL II), terminal lactosamine (RCA120 ), and α1,6 and α1,3 fucosylated oligosaccharides (PSA, LTA); oMSCs exhibited more T antigen (Jacalin), GalNAcα1,3(LFucα1,2)Galβ1,3/4GlcNAcβ1 (DBA), chitotriose (succinylated WGA), and α1,2-linked fucose (UEA I); and eMSCs showed a higher density of α2,6 sialic acids (SNA) and high mannose N-glycans (Con A). 28906588 7 42 theme acids 1533:1537 arg1 density 1510:1516 a higher density 1501:1516 a higher density of α2,6 sialic acids (SNA) 1501:1543 In addition, cMSCs expressed more α2,3-linked sialic acid (MAL II), terminal lactosamine (RCA120 ), and α1,6 and α1,3 fucosylated oligosaccharides (PSA, LTA); oMSCs exhibited more T antigen (Jacalin), GalNAcα1,3(LFucα1,2)Galβ1,3/4GlcNAcβ1 (DBA), chitotriose (succinylated WGA), and α1,2-linked fucose (UEA I); and eMSCs showed a higher density of α2,6 sialic acids (SNA) and high mannose N-glycans (Con A). 28906588 7 42 theme acids 1533:1537 arg1 N-glycans 1562:1570 high mannose N-glycans 1549:1570 high mannose N-glycans (Con A) 1549:1578 In addition, cMSCs expressed more α2,3-linked sialic acid (MAL II), terminal lactosamine (RCA120 ), and α1,6 and α1,3 fucosylated oligosaccharides (PSA, LTA); oMSCs exhibited more T antigen (Jacalin), GalNAcα1,3(LFucα1,2)Galβ1,3/4GlcNAcβ1 (DBA), chitotriose (succinylated WGA), and α1,2-linked fucose (UEA I); and eMSCs showed a higher density of α2,6 sialic acids (SNA) and high mannose N-glycans (Con A). 28906588 7 42 theme acids 1533:1537 arg1 A 1577:1577 Con A 1573:1577 Con A 1573:1577 In addition, cMSCs expressed more α2,3-linked sialic acid (MAL II), terminal lactosamine (RCA120 ), and α1,6 and α1,3 fucosylated oligosaccharides (PSA, LTA); oMSCs exhibited more T antigen (Jacalin), GalNAcα1,3(LFucα1,2)Galβ1,3/4GlcNAcβ1 (DBA), chitotriose (succinylated WGA), and α1,2-linked fucose (UEA I); and eMSCs showed a higher density of α2,6 sialic acids (SNA) and high mannose N-glycans (Con A). 28906588 7 43 theme α2,6 1521:1524 arg1 acids 1533:1537 α2,6 sialic acids 1521:1537 α2,6 sialic acids 1521:1537 In addition, cMSCs expressed more α2,3-linked sialic acid (MAL II), terminal lactosamine (RCA120 ), and α1,6 and α1,3 fucosylated oligosaccharides (PSA, LTA); oMSCs exhibited more T antigen (Jacalin), GalNAcα1,3(LFucα1,2)Galβ1,3/4GlcNAcβ1 (DBA), chitotriose (succinylated WGA), and α1,2-linked fucose (UEA I); and eMSCs showed a higher density of α2,6 sialic acids (SNA) and high mannose N-glycans (Con A). 28906588 2 44 theme promising 454:462 arg1 candidates 464:473 promising candidates 454:473 promising candidates as cell biomarkers 454:492 Recent studies demonstrated that the glycans in the glycocalyx of MSCs are promising candidates as cell biomarkers. 28906588 2 44 theme promising 454:462 arg1 glycans 416:422 the glycans 412:422 the glycans in the glycocalyx of MSCs 412:448 Recent studies demonstrated that the glycans in the glycocalyx of MSCs are promising candidates as cell biomarkers. 28906588 1 45 link marrow-derived 112:125 arg1 MSCs 151:154 MSCs 151:154 MSCs 151:154 The use of bone marrow-derived mesenchymal stem cells (MSCs) for clinical and experimental studies is increasing, but full characterization of MSCs in veterinary species is hindered by the variability in species-specific cell surface marker expression and antibody cross reactivity. 28906588 1 45 link marrow-derived 112:125 arg1 cells 144:148 bone marrow-derived mesenchymal stem cells 107:148 bone marrow-derived mesenchymal stem cells (MSCs) 107:155 The use of bone marrow-derived mesenchymal stem cells (MSCs) for clinical and experimental studies is increasing, but full characterization of MSCs in veterinary species is hindered by the variability in species-specific cell surface marker expression and antibody cross reactivity. 28906588 0 46 theme canine 26:31 arg1 pattern 15:21 Surface glycan pattern 0:21 Surface glycan pattern of canine, equine, and ovine bone marrow-derived mesenchymal stem cells 0:93 Surface glycan pattern of canine, equine, and ovine bone marrow-derived mesenchymal stem cells. 28906588 0 47 link marrow-derived 57:70 arg1 cells 89:93 ovine bone marrow-derived mesenchymal stem cells 46:93 ovine bone marrow-derived mesenchymal stem cells 46:93 Surface glycan pattern of canine, equine, and ovine bone marrow-derived mesenchymal stem cells. 28906588 8 48 gly glycosylation 1675:1687 arg1 oMSC 1707:1710 oMSC 1707:1710 oMSC 1707:1710 Using cell microarray methodology, we have for the first time demonstrated differences in the glycosylation profiles of cMSC, oMSC, and eMSC surfaces. 28906588 8 48 gly glycosylation 1675:1687 arg1 cMSC 1701:1704 cMSC 1701:1704 cMSC 1701:1704 Using cell microarray methodology, we have for the first time demonstrated differences in the glycosylation profiles of cMSC, oMSC, and eMSC surfaces. 28906588 8 48 gly glycosylation 1675:1687 arg1 surfaces 1722:1729 eMSC surfaces 1717:1729 eMSC surfaces 1717:1729 Using cell microarray methodology, we have for the first time demonstrated differences in the glycosylation profiles of cMSC, oMSC, and eMSC surfaces. 28906588 0 49 theme equine 34:39 arg1 pattern 15:21 Surface glycan pattern 0:21 Surface glycan pattern of canine, equine, and ovine bone marrow-derived mesenchymal stem cells 0:93 Surface glycan pattern of canine, equine, and ovine bone marrow-derived mesenchymal stem cells. 28906588 5 50 theme glycan 965:970 arg1 types 972:976 O-linked glycan types 956:976 O-linked glycan types 956:976 The lectin-binding signals indicated that the MSC surface of the investigated species contained both N- and O-linked glycan types, with N-glycosylation predominating over O-glycosylation and fucosylation being more abundant than sialylation. 28906588 7 51 theme terminal 1242:1249 arg1 RCA120 1264:1269 RCA120 1264:1269 RCA120 1264:1269 In addition, cMSCs expressed more α2,3-linked sialic acid (MAL II), terminal lactosamine (RCA120 ), and α1,6 and α1,3 fucosylated oligosaccharides (PSA, LTA); oMSCs exhibited more T antigen (Jacalin), GalNAcα1,3(LFucα1,2)Galβ1,3/4GlcNAcβ1 (DBA), chitotriose (succinylated WGA), and α1,2-linked fucose (UEA I); and eMSCs showed a higher density of α2,6 sialic acids (SNA) and high mannose N-glycans (Con A). 28906588 7 51 theme terminal 1242:1249 arg1 lactosamine 1251:1261 terminal lactosamine 1242:1261 terminal lactosamine (RCA120 ) 1242:1271 In addition, cMSCs expressed more α2,3-linked sialic acid (MAL II), terminal lactosamine (RCA120 ), and α1,6 and α1,3 fucosylated oligosaccharides (PSA, LTA); oMSCs exhibited more T antigen (Jacalin), GalNAcα1,3(LFucα1,2)Galβ1,3/4GlcNAcβ1 (DBA), chitotriose (succinylated WGA), and α1,2-linked fucose (UEA I); and eMSCs showed a higher density of α2,6 sialic acids (SNA) and high mannose N-glycans (Con A). 28906588 5 52 theme species 926:932 arg1 surface 898:904 the MSC surface 890:904 the MSC surface of the investigated species 890:932 The lectin-binding signals indicated that the MSC surface of the investigated species contained both N- and O-linked glycan types, with N-glycosylation predominating over O-glycosylation and fucosylation being more abundant than sialylation. 28906588 3 53 theme MSCs 599:602 arg1 glycocalyx 533:542 the glycocalyx 529:542 the glycocalyx of canine MSCs (cMSCs), ovine MSCs (oMSCs), and equine MSCs (eMSCs) 529:610 In the present study, we analyzed the glycocalyx of canine MSCs (cMSCs), ovine MSCs (oMSCs), and equine MSCs (eMSCs) using a cell microarray procedure in which MSCs were spotted on microarray slides and incubated with a panel of 14 biotinylated lectins and Cy3-conjugated streptavidin. 28906588 2 54 theme MSCs 445:448 arg1 glycocalyx 431:440 the glycocalyx 427:440 the glycocalyx of MSCs 427:448 Recent studies demonstrated that the glycans in the glycocalyx of MSCs are promising candidates as cell biomarkers. 28906588 3 55 theme cell 620:623 arg1 procedure 636:644 a cell microarray procedure 618:644 a cell microarray procedure in which MSCs were spotted on microarray slides and incubated with a panel of 14 biotinylated lectins and Cy3-conjugated streptavidin 618:778 In the present study, we analyzed the glycocalyx of canine MSCs (cMSCs), ovine MSCs (oMSCs), and equine MSCs (eMSCs) using a cell microarray procedure in which MSCs were spotted on microarray slides and incubated with a panel of 14 biotinylated lectins and Cy3-conjugated streptavidin. 28906588 8 56 theme cMSC 1701:1704 arg1 profiles 1689:1696 the glycosylation profiles 1671:1696 the glycosylation profiles of cMSC, oMSC, and eMSC surfaces 1671:1729 Using cell microarray methodology, we have for the first time demonstrated differences in the glycosylation profiles of cMSC, oMSC, and eMSC surfaces. 28906588 1 57 theme full 214:217 arg1 characterization 219:234 full characterization 214:234 full characterization of MSCs in veterinary species 214:264 The use of bone marrow-derived mesenchymal stem cells (MSCs) for clinical and experimental studies is increasing, but full characterization of MSCs in veterinary species is hindered by the variability in species-specific cell surface marker expression and antibody cross reactivity. 28906588 7 58 theme LFucα1,2 1386:1393 arg1 DBA 1414:1416 DBA 1414:1416 DBA 1414:1416 In addition, cMSCs expressed more α2,3-linked sialic acid (MAL II), terminal lactosamine (RCA120 ), and α1,6 and α1,3 fucosylated oligosaccharides (PSA, LTA); oMSCs exhibited more T antigen (Jacalin), GalNAcα1,3(LFucα1,2)Galβ1,3/4GlcNAcβ1 (DBA), chitotriose (succinylated WGA), and α1,2-linked fucose (UEA I); and eMSCs showed a higher density of α2,6 sialic acids (SNA) and high mannose N-glycans (Con A). 28906588 7 58 theme LFucα1,2 1386:1393 arg1 Galβ1,3/4GlcNAcβ1 1395:1411 GalNAcα1,3(LFucα1,2)Galβ1,3/4GlcNAcβ1 1375:1411 GalNAcα1,3(LFucα1,2)Galβ1,3/4GlcNAcβ1 (DBA) 1375:1417 In addition, cMSCs expressed more α2,3-linked sialic acid (MAL II), terminal lactosamine (RCA120 ), and α1,6 and α1,3 fucosylated oligosaccharides (PSA, LTA); oMSCs exhibited more T antigen (Jacalin), GalNAcα1,3(LFucα1,2)Galβ1,3/4GlcNAcβ1 (DBA), chitotriose (succinylated WGA), and α1,2-linked fucose (UEA I); and eMSCs showed a higher density of α2,6 sialic acids (SNA) and high mannose N-glycans (Con A). 28906588 4 59 theme signal 785:790 arg1 intensity 792:800 The signal intensity 781:800 The signal intensity 781:800 The signal intensity was then detected using a microarray scanner. 28906588 8 60 theme oMSC 1707:1710 arg1 profiles 1689:1696 the glycosylation profiles 1671:1696 the glycosylation profiles of cMSC, oMSC, and eMSC surfaces 1671:1729 Using cell microarray methodology, we have for the first time demonstrated differences in the glycosylation profiles of cMSC, oMSC, and eMSC surfaces. 28906588 7 61 theme GalNAcα1,3 1375:1384 arg1 DBA 1414:1416 DBA 1414:1416 DBA 1414:1416 In addition, cMSCs expressed more α2,3-linked sialic acid (MAL II), terminal lactosamine (RCA120 ), and α1,6 and α1,3 fucosylated oligosaccharides (PSA, LTA); oMSCs exhibited more T antigen (Jacalin), GalNAcα1,3(LFucα1,2)Galβ1,3/4GlcNAcβ1 (DBA), chitotriose (succinylated WGA), and α1,2-linked fucose (UEA I); and eMSCs showed a higher density of α2,6 sialic acids (SNA) and high mannose N-glycans (Con A). 28906588 7 61 theme GalNAcα1,3 1375:1384 arg1 Galβ1,3/4GlcNAcβ1 1395:1411 GalNAcα1,3(LFucα1,2)Galβ1,3/4GlcNAcβ1 1375:1411 GalNAcα1,3(LFucα1,2)Galβ1,3/4GlcNAcβ1 (DBA) 1375:1417 In addition, cMSCs expressed more α2,3-linked sialic acid (MAL II), terminal lactosamine (RCA120 ), and α1,6 and α1,3 fucosylated oligosaccharides (PSA, LTA); oMSCs exhibited more T antigen (Jacalin), GalNAcα1,3(LFucα1,2)Galβ1,3/4GlcNAcβ1 (DBA), chitotriose (succinylated WGA), and α1,2-linked fucose (UEA I); and eMSCs showed a higher density of α2,6 sialic acids (SNA) and high mannose N-glycans (Con A). 28906588 7 62 dep exhibited 1339:1347 arg1 UEA 1476:1478 UEA I 1476:1480 UEA I 1476:1480 In addition, cMSCs expressed more α2,3-linked sialic acid (MAL II), terminal lactosamine (RCA120 ), and α1,6 and α1,3 fucosylated oligosaccharides (PSA, LTA); oMSCs exhibited more T antigen (Jacalin), GalNAcα1,3(LFucα1,2)Galβ1,3/4GlcNAcβ1 (DBA), chitotriose (succinylated WGA), and α1,2-linked fucose (UEA I); and eMSCs showed a higher density of α2,6 sialic acids (SNA) and high mannose N-glycans (Con A). 28906588 7 62 dep exhibited 1339:1347 arg1 LTA 1327:1329 LTA 1327:1329 LTA 1327:1329 In addition, cMSCs expressed more α2,3-linked sialic acid (MAL II), terminal lactosamine (RCA120 ), and α1,6 and α1,3 fucosylated oligosaccharides (PSA, LTA); oMSCs exhibited more T antigen (Jacalin), GalNAcα1,3(LFucα1,2)Galβ1,3/4GlcNAcβ1 (DBA), chitotriose (succinylated WGA), and α1,2-linked fucose (UEA I); and eMSCs showed a higher density of α2,6 sialic acids (SNA) and high mannose N-glycans (Con A). 28906588 7 62 dep exhibited 1339:1347 arg1 PSA 1322:1324 PSA 1322:1324 PSA 1322:1324 In addition, cMSCs expressed more α2,3-linked sialic acid (MAL II), terminal lactosamine (RCA120 ), and α1,6 and α1,3 fucosylated oligosaccharides (PSA, LTA); oMSCs exhibited more T antigen (Jacalin), GalNAcα1,3(LFucα1,2)Galβ1,3/4GlcNAcβ1 (DBA), chitotriose (succinylated WGA), and α1,2-linked fucose (UEA I); and eMSCs showed a higher density of α2,6 sialic acids (SNA) and high mannose N-glycans (Con A). 28906588 7 62 dep exhibited 1339:1347 arg1 cMSCs 1187:1191 cMSCs 1187:1191 cMSCs expressed more α2,3-linked sialic acid (MAL II), terminal lactosamine (RCA120 ), and α1,6 and α1,3 fucosylated oligosaccharides 1187:1319 In addition, cMSCs expressed more α2,3-linked sialic acid (MAL II), terminal lactosamine (RCA120 ), and α1,6 and α1,3 fucosylated oligosaccharides (PSA, LTA); oMSCs exhibited more T antigen (Jacalin), GalNAcα1,3(LFucα1,2)Galβ1,3/4GlcNAcβ1 (DBA), chitotriose (succinylated WGA), and α1,2-linked fucose (UEA I); and eMSCs showed a higher density of α2,6 sialic acids (SNA) and high mannose N-glycans (Con A). 28906588 8 63 theme surfaces 1722:1729 arg1 profiles 1689:1696 the glycosylation profiles 1671:1696 the glycosylation profiles of cMSC, oMSC, and eMSC surfaces 1671:1729 Using cell microarray methodology, we have for the first time demonstrated differences in the glycosylation profiles of cMSC, oMSC, and eMSC surfaces. 28906588 1 64 theme clinical 161:168 arg1 studies 187:193 clinical and experimental studies 161:193 clinical and experimental studies 161:193 The use of bone marrow-derived mesenchymal stem cells (MSCs) for clinical and experimental studies is increasing, but full characterization of MSCs in veterinary species is hindered by the variability in species-specific cell surface marker expression and antibody cross reactivity. 28906588 1 65 theme experimental 174:185 arg1 studies 187:193 clinical and experimental studies 161:193 clinical and experimental studies 161:193 The use of bone marrow-derived mesenchymal stem cells (MSCs) for clinical and experimental studies is increasing, but full characterization of MSCs in veterinary species is hindered by the variability in species-specific cell surface marker expression and antibody cross reactivity. 28906588 3 66 theme MSCs 554:557 arg1 glycocalyx 533:542 the glycocalyx 529:542 the glycocalyx of canine MSCs (cMSCs), ovine MSCs (oMSCs), and equine MSCs (eMSCs) 529:610 In the present study, we analyzed the glycocalyx of canine MSCs (cMSCs), ovine MSCs (oMSCs), and equine MSCs (eMSCs) using a cell microarray procedure in which MSCs were spotted on microarray slides and incubated with a panel of 14 biotinylated lectins and Cy3-conjugated streptavidin. 28906588 8 67 theme cell 1587:1590 arg1 methodology 1603:1613 cell microarray methodology 1587:1613 cell microarray methodology 1587:1613 Using cell microarray methodology, we have for the first time demonstrated differences in the glycosylation profiles of cMSC, oMSC, and eMSC surfaces. 28906588 3 68 theme MSCs 574:577 arg1 glycocalyx 533:542 the glycocalyx 529:542 the glycocalyx of canine MSCs (cMSCs), ovine MSCs (oMSCs), and equine MSCs (eMSCs) 529:610 In the present study, we analyzed the glycocalyx of canine MSCs (cMSCs), ovine MSCs (oMSCs), and equine MSCs (eMSCs) using a cell microarray procedure in which MSCs were spotted on microarray slides and incubated with a panel of 14 biotinylated lectins and Cy3-conjugated streptavidin. 28906588 0 69 theme ovine 46:50 arg1 cells 89:93 ovine bone marrow-derived mesenchymal stem cells 46:93 ovine bone marrow-derived mesenchymal stem cells 46:93 Surface glycan pattern of canine, equine, and ovine bone marrow-derived mesenchymal stem cells. 28906588 1 70 theme marrow-derived 112:125 arg1 MSCs 151:154 MSCs 151:154 MSCs 151:154 The use of bone marrow-derived mesenchymal stem cells (MSCs) for clinical and experimental studies is increasing, but full characterization of MSCs in veterinary species is hindered by the variability in species-specific cell surface marker expression and antibody cross reactivity. 28906588 1 70 theme marrow-derived 112:125 arg1 cells 144:148 bone marrow-derived mesenchymal stem cells 107:148 bone marrow-derived mesenchymal stem cells (MSCs) 107:155 The use of bone marrow-derived mesenchymal stem cells (MSCs) for clinical and experimental studies is increasing, but full characterization of MSCs in veterinary species is hindered by the variability in species-specific cell surface marker expression and antibody cross reactivity. 28906588 3 71 theme streptavidin 767:778 arg1 panel 715:719 a panel 713:719 a panel of 14 biotinylated lectins and Cy3-conjugated streptavidin 713:778 In the present study, we analyzed the glycocalyx of canine MSCs (cMSCs), ovine MSCs (oMSCs), and equine MSCs (eMSCs) using a cell microarray procedure in which MSCs were spotted on microarray slides and incubated with a panel of 14 biotinylated lectins and Cy3-conjugated streptavidin. 28906588 2 72 theme cell 478:481 arg1 biomarkers 483:492 cell biomarkers 478:492 cell biomarkers 478:492 Recent studies demonstrated that the glycans in the glycocalyx of MSCs are promising candidates as cell biomarkers. 28906588 7 73 theme fucosylated 1292:1302 arg1 oligosaccharides 1304:1319 α1,3 fucosylated oligosaccharides 1287:1319 α1,3 fucosylated oligosaccharides 1287:1319 In addition, cMSCs expressed more α2,3-linked sialic acid (MAL II), terminal lactosamine (RCA120 ), and α1,6 and α1,3 fucosylated oligosaccharides (PSA, LTA); oMSCs exhibited more T antigen (Jacalin), GalNAcα1,3(LFucα1,2)Galβ1,3/4GlcNAcβ1 (DBA), chitotriose (succinylated WGA), and α1,2-linked fucose (UEA I); and eMSCs showed a higher density of α2,6 sialic acids (SNA) and high mannose N-glycans (Con A). 28906588 9 74 theme molecular 1820:1828 arg1 remodeling 1830:1839 molecular remodeling 1820:1839 molecular remodeling in clinical cell-based therapy and tissue engineering studies 1820:1901 These results could be valuable as resources and references for MSC differentiation and molecular remodeling in clinical cell-based therapy and tissue engineering studies. 28906588 0 75 theme marrow-derived 57:70 arg1 cells 89:93 ovine bone marrow-derived mesenchymal stem cells 46:93 ovine bone marrow-derived mesenchymal stem cells 46:93 Surface glycan pattern of canine, equine, and ovine bone marrow-derived mesenchymal stem cells. 28906588 1 76 theme species-specific 300:315 arg1 expression 337:346 species-specific cell surface marker expression 300:346 species-specific cell surface marker expression 300:346 The use of bone marrow-derived mesenchymal stem cells (MSCs) for clinical and experimental studies is increasing, but full characterization of MSCs in veterinary species is hindered by the variability in species-specific cell surface marker expression and antibody cross reactivity. 28906588 1 77 theme stem 139:142 arg1 MSCs 151:154 MSCs 151:154 MSCs 151:154 The use of bone marrow-derived mesenchymal stem cells (MSCs) for clinical and experimental studies is increasing, but full characterization of MSCs in veterinary species is hindered by the variability in species-specific cell surface marker expression and antibody cross reactivity. 28906588 1 77 theme stem 139:142 arg1 cells 144:148 bone marrow-derived mesenchymal stem cells 107:148 bone marrow-derived mesenchymal stem cells (MSCs) 107:155 The use of bone marrow-derived mesenchymal stem cells (MSCs) for clinical and experimental studies is increasing, but full characterization of MSCs in veterinary species is hindered by the variability in species-specific cell surface marker expression and antibody cross reactivity. 28906588 7 78 theme Con 1573:1575 arg1 N-glycans 1562:1570 high mannose N-glycans 1549:1570 high mannose N-glycans (Con A) 1549:1578 In addition, cMSCs expressed more α2,3-linked sialic acid (MAL II), terminal lactosamine (RCA120 ), and α1,6 and α1,3 fucosylated oligosaccharides (PSA, LTA); oMSCs exhibited more T antigen (Jacalin), GalNAcα1,3(LFucα1,2)Galβ1,3/4GlcNAcβ1 (DBA), chitotriose (succinylated WGA), and α1,2-linked fucose (UEA I); and eMSCs showed a higher density of α2,6 sialic acids (SNA) and high mannose N-glycans (Con A). 28906588 7 78 theme Con 1573:1575 arg1 A 1577:1577 Con A 1573:1577 Con A 1573:1577 In addition, cMSCs expressed more α2,3-linked sialic acid (MAL II), terminal lactosamine (RCA120 ), and α1,6 and α1,3 fucosylated oligosaccharides (PSA, LTA); oMSCs exhibited more T antigen (Jacalin), GalNAcα1,3(LFucα1,2)Galβ1,3/4GlcNAcβ1 (DBA), chitotriose (succinylated WGA), and α1,2-linked fucose (UEA I); and eMSCs showed a higher density of α2,6 sialic acids (SNA) and high mannose N-glycans (Con A). 28906588 7 79 theme α1,2-linked 1456:1466 arg1 fucose 1468:1473 α1,2-linked fucose 1456:1473 α1,2-linked fucose 1456:1473 In addition, cMSCs expressed more α2,3-linked sialic acid (MAL II), terminal lactosamine (RCA120 ), and α1,6 and α1,3 fucosylated oligosaccharides (PSA, LTA); oMSCs exhibited more T antigen (Jacalin), GalNAcα1,3(LFucα1,2)Galβ1,3/4GlcNAcβ1 (DBA), chitotriose (succinylated WGA), and α1,2-linked fucose (UEA I); and eMSCs showed a higher density of α2,6 sialic acids (SNA) and high mannose N-glycans (Con A). 28906588 0 80 theme stem 84:87 arg1 cells 89:93 ovine bone marrow-derived mesenchymal stem cells 46:93 ovine bone marrow-derived mesenchymal stem cells 46:93 Surface glycan pattern of canine, equine, and ovine bone marrow-derived mesenchymal stem cells. 28906588 1 81 theme surface 322:328 arg1 expression 337:346 species-specific cell surface marker expression 300:346 species-specific cell surface marker expression 300:346 The use of bone marrow-derived mesenchymal stem cells (MSCs) for clinical and experimental studies is increasing, but full characterization of MSCs in veterinary species is hindered by the variability in species-specific cell surface marker expression and antibody cross reactivity. 28906588 8 82 theme first 1632:1636 arg1 time 1638:1641 the first time 1628:1641 the first time 1628:1641 Using cell microarray methodology, we have for the first time demonstrated differences in the glycosylation profiles of cMSC, oMSC, and eMSC surfaces. 28906588 5 83 theme MSC 894:896 arg1 surface 898:904 the MSC surface 890:904 the MSC surface of the investigated species 890:932 The lectin-binding signals indicated that the MSC surface of the investigated species contained both N- and O-linked glycan types, with N-glycosylation predominating over O-glycosylation and fucosylation being more abundant than sialylation. 28906588 7 84 link α1,2-linked 1456:1466 arg1 fucose 1468:1473 α1,2-linked fucose 1456:1473 α1,2-linked fucose 1456:1473 In addition, cMSCs expressed more α2,3-linked sialic acid (MAL II), terminal lactosamine (RCA120 ), and α1,6 and α1,3 fucosylated oligosaccharides (PSA, LTA); oMSCs exhibited more T antigen (Jacalin), GalNAcα1,3(LFucα1,2)Galβ1,3/4GlcNAcβ1 (DBA), chitotriose (succinylated WGA), and α1,2-linked fucose (UEA I); and eMSCs showed a higher density of α2,6 sialic acids (SNA) and high mannose N-glycans (Con A). 28906588 3 85 theme biotinylated 727:738 arg1 lectins 740:746 14 biotinylated lectins 724:746 14 biotinylated lectins 724:746 In the present study, we analyzed the glycocalyx of canine MSCs (cMSCs), ovine MSCs (oMSCs), and equine MSCs (eMSCs) using a cell microarray procedure in which MSCs were spotted on microarray slides and incubated with a panel of 14 biotinylated lectins and Cy3-conjugated streptavidin. 28906588 7 86 theme high 1549:1552 arg1 N-glycans 1562:1570 high mannose N-glycans 1549:1570 high mannose N-glycans (Con A) 1549:1578 In addition, cMSCs expressed more α2,3-linked sialic acid (MAL II), terminal lactosamine (RCA120 ), and α1,6 and α1,3 fucosylated oligosaccharides (PSA, LTA); oMSCs exhibited more T antigen (Jacalin), GalNAcα1,3(LFucα1,2)Galβ1,3/4GlcNAcβ1 (DBA), chitotriose (succinylated WGA), and α1,2-linked fucose (UEA I); and eMSCs showed a higher density of α2,6 sialic acids (SNA) and high mannose N-glycans (Con A). 28906588 7 86 theme high 1549:1552 arg1 A 1577:1577 Con A 1573:1577 Con A 1573:1577 In addition, cMSCs expressed more α2,3-linked sialic acid (MAL II), terminal lactosamine (RCA120 ), and α1,6 and α1,3 fucosylated oligosaccharides (PSA, LTA); oMSCs exhibited more T antigen (Jacalin), GalNAcα1,3(LFucα1,2)Galβ1,3/4GlcNAcβ1 (DBA), chitotriose (succinylated WGA), and α1,2-linked fucose (UEA I); and eMSCs showed a higher density of α2,6 sialic acids (SNA) and high mannose N-glycans (Con A). 28906588 0 87 theme glycan 8:13 arg1 pattern 15:21 Surface glycan pattern 0:21 Surface glycan pattern of canine, equine, and ovine bone marrow-derived mesenchymal stem cells 0:93 Surface glycan pattern of canine, equine, and ovine bone marrow-derived mesenchymal stem cells. 28906588 1 88 theme antibody 352:359 arg1 reactivity 367:376 antibody cross reactivity 352:376 antibody cross reactivity 352:376 The use of bone marrow-derived mesenchymal stem cells (MSCs) for clinical and experimental studies is increasing, but full characterization of MSCs in veterinary species is hindered by the variability in species-specific cell surface marker expression and antibody cross reactivity. 28906588 9 89 from differentiation 1800:1814 arg1 therapy 1864:1870 clinical cell-based therapy 1844:1870 clinical cell-based therapy 1844:1870 These results could be valuable as resources and references for MSC differentiation and molecular remodeling in clinical cell-based therapy and tissue engineering studies. 28906588 9 89 from differentiation 1800:1814 arg1 studies 1895:1901 tissue engineering studies 1876:1901 tissue engineering studies 1876:1901 These results could be valuable as resources and references for MSC differentiation and molecular remodeling in clinical cell-based therapy and tissue engineering studies. 28906588 9 90 theme engineering 1883:1893 arg1 studies 1895:1901 tissue engineering studies 1876:1901 tissue engineering studies 1876:1901 These results could be valuable as resources and references for MSC differentiation and molecular remodeling in clinical cell-based therapy and tissue engineering studies. 28906588 1 91 theme veterinary 247:256 arg1 species 258:264 veterinary species 247:264 veterinary species 247:264 The use of bone marrow-derived mesenchymal stem cells (MSCs) for clinical and experimental studies is increasing, but full characterization of MSCs in veterinary species is hindered by the variability in species-specific cell surface marker expression and antibody cross reactivity. 28906588 8 92 theme glycosylation 1675:1687 arg1 profiles 1689:1696 the glycosylation profiles 1671:1696 the glycosylation profiles of cMSC, oMSC, and eMSC surfaces 1671:1729 Using cell microarray methodology, we have for the first time demonstrated differences in the glycosylation profiles of cMSC, oMSC, and eMSC surfaces. 28906588 7 93 theme sialic 1526:1531 arg1 acids 1533:1537 α2,6 sialic acids 1521:1537 α2,6 sialic acids 1521:1537 In addition, cMSCs expressed more α2,3-linked sialic acid (MAL II), terminal lactosamine (RCA120 ), and α1,6 and α1,3 fucosylated oligosaccharides (PSA, LTA); oMSCs exhibited more T antigen (Jacalin), GalNAcα1,3(LFucα1,2)Galβ1,3/4GlcNAcβ1 (DBA), chitotriose (succinylated WGA), and α1,2-linked fucose (UEA I); and eMSCs showed a higher density of α2,6 sialic acids (SNA) and high mannose N-glycans (Con A). 28906588 7 94 theme succinylated 1433:1444 arg1 chitotriose 1420:1430 chitotriose 1420:1430 chitotriose (succinylated WGA) 1420:1449 In addition, cMSCs expressed more α2,3-linked sialic acid (MAL II), terminal lactosamine (RCA120 ), and α1,6 and α1,3 fucosylated oligosaccharides (PSA, LTA); oMSCs exhibited more T antigen (Jacalin), GalNAcα1,3(LFucα1,2)Galβ1,3/4GlcNAcβ1 (DBA), chitotriose (succinylated WGA), and α1,2-linked fucose (UEA I); and eMSCs showed a higher density of α2,6 sialic acids (SNA) and high mannose N-glycans (Con A). 28906588 7 94 theme succinylated 1433:1444 arg1 WGA 1446:1448 succinylated WGA 1433:1448 succinylated WGA 1433:1448 In addition, cMSCs expressed more α2,3-linked sialic acid (MAL II), terminal lactosamine (RCA120 ), and α1,6 and α1,3 fucosylated oligosaccharides (PSA, LTA); oMSCs exhibited more T antigen (Jacalin), GalNAcα1,3(LFucα1,2)Galβ1,3/4GlcNAcβ1 (DBA), chitotriose (succinylated WGA), and α1,2-linked fucose (UEA I); and eMSCs showed a higher density of α2,6 sialic acids (SNA) and high mannose N-glycans (Con A). 28906588 5 95 theme O-linked 956:963 arg1 types 972:976 O-linked glycan types 956:976 O-linked glycan types 956:976 The lectin-binding signals indicated that the MSC surface of the investigated species contained both N- and O-linked glycan types, with N-glycosylation predominating over O-glycosylation and fucosylation being more abundant than sialylation. 28906588 6 96 theme Relative 1090:1097 arg1 quantification 1099:1112 Relative quantification 1090:1112 Relative quantification 1090:1112 Relative quantification revealed an interspecific difference between these glycans. 28906588 5 97 theme investigated 913:924 arg1 species 926:932 the investigated species 909:932 the investigated species 909:932 The lectin-binding signals indicated that the MSC surface of the investigated species contained both N- and O-linked glycan types, with N-glycosylation predominating over O-glycosylation and fucosylation being more abundant than sialylation. 28906588 3 98 theme equine 592:597 arg1 MSCs 599:602 equine MSCs 592:602 equine MSCs (eMSCs) 592:610 In the present study, we analyzed the glycocalyx of canine MSCs (cMSCs), ovine MSCs (oMSCs), and equine MSCs (eMSCs) using a cell microarray procedure in which MSCs were spotted on microarray slides and incubated with a panel of 14 biotinylated lectins and Cy3-conjugated streptavidin. 28906588 3 98 theme equine 592:597 arg1 eMSCs 605:609 eMSCs 605:609 eMSCs 605:609 In the present study, we analyzed the glycocalyx of canine MSCs (cMSCs), ovine MSCs (oMSCs), and equine MSCs (eMSCs) using a cell microarray procedure in which MSCs were spotted on microarray slides and incubated with a panel of 14 biotinylated lectins and Cy3-conjugated streptavidin. 28906588 3 99 theme present 502:508 arg1 study 510:514 the present study 498:514 the present study 498:514 In the present study, we analyzed the glycocalyx of canine MSCs (cMSCs), ovine MSCs (oMSCs), and equine MSCs (eMSCs) using a cell microarray procedure in which MSCs were spotted on microarray slides and incubated with a panel of 14 biotinylated lectins and Cy3-conjugated streptavidin. 28314751 3 0 theme I-associated 302:313 arg1 antigens 323:330 36 MHC class I-associated peptide antigens 289:330 36 MHC class I-associated peptide antigens with O-linked β-N-acetylglucosamine (O-GlcNAc) modifications 289:391 Here, we identify 36 MHC class I-associated peptide antigens with O-linked β-N-acetylglucosamine (O-GlcNAc) modifications as candidate neoantigens, using three experimental approaches. 28314751 3 0 theme I-associated 302:313 arg1 neoantigens 406:416 candidate neoantigens 396:416 candidate neoantigens 396:416 Here, we identify 36 MHC class I-associated peptide antigens with O-linked β-N-acetylglucosamine (O-GlcNAc) modifications as candidate neoantigens, using three experimental approaches. 28314751 7 1 theme unmodified 1033:1042 arg1 peptide 1044:1050 the equivalent unmodified peptide 1018:1050 the equivalent unmodified peptide 1018:1050 An O-GlcNAc-specific T-cell line specifically killed autologous cells pulsed with the modified peptide, but not the equivalent unmodified peptide. 28314751 3 2 theme peptide 315:321 arg1 antigens 323:330 36 MHC class I-associated peptide antigens 289:330 36 MHC class I-associated peptide antigens with O-linked β-N-acetylglucosamine (O-GlcNAc) modifications 289:391 Here, we identify 36 MHC class I-associated peptide antigens with O-linked β-N-acetylglucosamine (O-GlcNAc) modifications as candidate neoantigens, using three experimental approaches. 28314751 3 2 theme peptide 315:321 arg1 neoantigens 406:416 candidate neoantigens 396:416 candidate neoantigens 396:416 Here, we identify 36 MHC class I-associated peptide antigens with O-linked β-N-acetylglucosamine (O-GlcNAc) modifications as candidate neoantigens, using three experimental approaches. 28314751 1 3 contain have 132:135 arg1 they 127:130 they 127:130 they 127:130 Leukemias are highly immunogenic, but they have a low mutational load, providing few mutated peptide targets. 28314751 1 3 contain have 132:135 arg2 load 154:157 a low mutational load 137:157 a low mutational load 137:157 Leukemias are highly immunogenic, but they have a low mutational load, providing few mutated peptide targets. 28314751 7 4 theme autologous 959:968 arg1 cells 970:974 autologous cells 959:974 autologous cells pulsed with the modified peptide, but not the equivalent unmodified peptide 959:1050 An O-GlcNAc-specific T-cell line specifically killed autologous cells pulsed with the modified peptide, but not the equivalent unmodified peptide. 28314751 4 5 theme arginine 597:604 arg1 residues 606:613 either mono- and/or di-methylated arginine residues 563:613 either mono- and/or di-methylated arginine residues 563:613 Thirteen of these peptides were also detected with disaccharide units on the same residues and two contain either mono- and/or di-methylated arginine residues. 28314751 3 6 link O-linked 337:344 arg1 modifications 379:391 O-linked β-N-acetylglucosamine (O-GlcNAc) modifications 337:391 O-linked β-N-acetylglucosamine (O-GlcNAc) modifications 337:391 Here, we identify 36 MHC class I-associated peptide antigens with O-linked β-N-acetylglucosamine (O-GlcNAc) modifications as candidate neoantigens, using three experimental approaches. 28314751 10 7 theme ©2017 1195:1199 arg1 AACR 1201:1204 ©2017 AACR 1195:1204 ©2017 AACR. 1195:1205 ©2017 AACR. 28314751 3 8 theme O-GlcNAc 369:376 arg1 modifications 379:391 O-linked β-N-acetylglucosamine (O-GlcNAc) modifications 337:391 O-linked β-N-acetylglucosamine (O-GlcNAc) modifications 337:391 Here, we identify 36 MHC class I-associated peptide antigens with O-linked β-N-acetylglucosamine (O-GlcNAc) modifications as candidate neoantigens, using three experimental approaches. 28314751 4 9 contain contain 555:561 arg1 two 551:553 two 551:553 two 551:553 Thirteen of these peptides were also detected with disaccharide units on the same residues and two contain either mono- and/or di-methylated arginine residues. 28314751 4 9 contain contain 555:561 arg2 residues 606:613 either mono- and/or di-methylated arginine residues 563:613 either mono- and/or di-methylated arginine residues 563:613 Thirteen of these peptides were also detected with disaccharide units on the same residues and two contain either mono- and/or di-methylated arginine residues. 28314751 3 10 theme O-linked 337:344 arg1 modifications 379:391 O-linked β-N-acetylglucosamine (O-GlcNAc) modifications 337:391 O-linked β-N-acetylglucosamine (O-GlcNAc) modifications 337:391 Here, we identify 36 MHC class I-associated peptide antigens with O-linked β-N-acetylglucosamine (O-GlcNAc) modifications as candidate neoantigens, using three experimental approaches. 28314751 0 11 from Neoantigens 64:74 arg1 Leukemia 79:86 Leukemia 79:86 Leukemia 79:86 Identification of Glycopeptides as Posttranslationally Modified Neoantigens in Leukemia. 28314751 5 12 theme key 642:644 arg1 pathways 653:660 key cancer pathways 642:660 key cancer pathways 642:660 A subset were linked with key cancer pathways, and these peptides were shared across all of the leukemia patient samples tested (5/5). 28314751 8 13 theme logical 1119:1125 arg1 targets 1127:1133 logical targets 1119:1133 logical targets for cancer immunotherapy 1119:1158 Therefore, these posttranslationally modified neoantigens provide logical targets for cancer immunotherapy. 28314751 1 14 theme peptide 182:188 arg1 targets 190:196 few mutated peptide targets 170:196 few mutated peptide targets 170:196 Leukemias are highly immunogenic, but they have a low mutational load, providing few mutated peptide targets. 28314751 1 15 theme few 170:172 arg1 targets 190:196 few mutated peptide targets 170:196 few mutated peptide targets 170:196 Leukemias are highly immunogenic, but they have a low mutational load, providing few mutated peptide targets. 28314751 3 16 theme β-N-acetylglucosamine 346:366 arg1 modifications 379:391 O-linked β-N-acetylglucosamine (O-GlcNAc) modifications 337:391 O-linked β-N-acetylglucosamine (O-GlcNAc) modifications 337:391 Here, we identify 36 MHC class I-associated peptide antigens with O-linked β-N-acetylglucosamine (O-GlcNAc) modifications as candidate neoantigens, using three experimental approaches. 28314751 4 17 theme disaccharide 507:518 arg1 units 520:524 disaccharide units 507:524 disaccharide units 507:524 Thirteen of these peptides were also detected with disaccharide units on the same residues and two contain either mono- and/or di-methylated arginine residues. 28314751 5 18 theme cancer 646:651 arg1 pathways 653:660 key cancer pathways 642:660 key cancer pathways 642:660 A subset were linked with key cancer pathways, and these peptides were shared across all of the leukemia patient samples tested (5/5). 28314751 7 19 theme T-cell 927:932 arg1 line 934:937 An O-GlcNAc-specific T-cell line 906:937 An O-GlcNAc-specific T-cell line 906:937 An O-GlcNAc-specific T-cell line specifically killed autologous cells pulsed with the modified peptide, but not the equivalent unmodified peptide. 28314751 1 20 theme mutated 174:180 arg1 targets 190:196 few mutated peptide targets 170:196 few mutated peptide targets 170:196 Leukemias are highly immunogenic, but they have a low mutational load, providing few mutated peptide targets. 28314751 6 21 theme multifunctional 847:861 arg1 responses 877:885 multifunctional memory T-cell responses 847:885 multifunctional memory T-cell responses in healthy donors 847:903 Seven of the O-GlcNAc peptides were synthesized and five (71%) were shown to be associated with multifunctional memory T-cell responses in healthy donors. 28314751 6 22 theme T-cell 870:875 arg1 responses 877:885 multifunctional memory T-cell responses 847:885 multifunctional memory T-cell responses in healthy donors 847:903 Seven of the O-GlcNAc peptides were synthesized and five (71%) were shown to be associated with multifunctional memory T-cell responses in healthy donors. 28314751 3 23 theme experimental 431:442 arg1 approaches 444:453 three experimental approaches 425:453 three experimental approaches 425:453 Here, we identify 36 MHC class I-associated peptide antigens with O-linked β-N-acetylglucosamine (O-GlcNAc) modifications as candidate neoantigens, using three experimental approaches. 28314751 3 24 theme candidate 396:404 arg1 antigens 323:330 36 MHC class I-associated peptide antigens 289:330 36 MHC class I-associated peptide antigens with O-linked β-N-acetylglucosamine (O-GlcNAc) modifications 289:391 Here, we identify 36 MHC class I-associated peptide antigens with O-linked β-N-acetylglucosamine (O-GlcNAc) modifications as candidate neoantigens, using three experimental approaches. 28314751 3 24 theme candidate 396:404 arg1 neoantigens 406:416 candidate neoantigens 396:416 candidate neoantigens 396:416 Here, we identify 36 MHC class I-associated peptide antigens with O-linked β-N-acetylglucosamine (O-GlcNAc) modifications as candidate neoantigens, using three experimental approaches. 28314751 4 25 theme mono- 570:574 arg1 residues 606:613 either mono- and/or di-methylated arginine residues 563:613 either mono- and/or di-methylated arginine residues 563:613 Thirteen of these peptides were also detected with disaccharide units on the same residues and two contain either mono- and/or di-methylated arginine residues. 28314751 6 26 theme peptides 773:780 arg1 Seven 751:755 Seven 751:755 Seven 751:755 Seven of the O-GlcNAc peptides were synthesized and five (71%) were shown to be associated with multifunctional memory T-cell responses in healthy donors. 28314751 6 26 theme peptides 773:780 arg1 peptides 773:780 the O-GlcNAc peptides 760:780 the O-GlcNAc peptides 760:780 Seven of the O-GlcNAc peptides were synthesized and five (71%) were shown to be associated with multifunctional memory T-cell responses in healthy donors. 28314751 8 27 theme modified 1090:1097 arg1 neoantigens 1099:1109 these posttranslationally modified neoantigens 1064:1109 these posttranslationally modified neoantigens 1064:1109 Therefore, these posttranslationally modified neoantigens provide logical targets for cancer immunotherapy. 28314751 6 28 theme O-GlcNAc 764:771 arg1 peptides 773:780 the O-GlcNAc peptides 760:780 the O-GlcNAc peptides 760:780 Seven of the O-GlcNAc peptides were synthesized and five (71%) were shown to be associated with multifunctional memory T-cell responses in healthy donors. 28314751 0 29 theme Glycopeptides 18:30 arg1 Identification 0:13 Identification 0:13 Identification of Glycopeptides as Posttranslationally Modified Neoantigens in Leukemia. 0:87 Identification of Glycopeptides as Posttranslationally Modified Neoantigens in Leukemia. 28314751 4 30 theme di-methylated 583:595 arg1 residues 606:613 either mono- and/or di-methylated arginine residues 563:613 either mono- and/or di-methylated arginine residues 563:613 Thirteen of these peptides were also detected with disaccharide units on the same residues and two contain either mono- and/or di-methylated arginine residues. 28314751 5 31 theme leukemia 712:719 arg1 5/5 745:747 5/5 745:747 5/5 745:747 A subset were linked with key cancer pathways, and these peptides were shared across all of the leukemia patient samples tested (5/5). 28314751 5 31 theme leukemia 712:719 arg1 samples 729:735 the leukemia patient samples 708:735 the leukemia patient samples tested (5/5) 708:748 A subset were linked with key cancer pathways, and these peptides were shared across all of the leukemia patient samples tested (5/5). 28314751 9 32 dep Res 1176:1178 arg1 Cancer 1161:1166 Cancer 1161:1166 Cancer 1161:1166 Cancer Immunol Res; 5(5); 376-84. 28314751 0 33 theme Modified 55:62 arg1 Neoantigens 64:74 Posttranslationally Modified Neoantigens 35:74 Posttranslationally Modified Neoantigens in Leukemia 35:86 Identification of Glycopeptides as Posttranslationally Modified Neoantigens in Leukemia. 28314751 5 34 theme patient 721:727 arg1 5/5 745:747 5/5 745:747 5/5 745:747 A subset were linked with key cancer pathways, and these peptides were shared across all of the leukemia patient samples tested (5/5). 28314751 5 34 theme patient 721:727 arg1 samples 729:735 the leukemia patient samples 708:735 the leukemia patient samples tested (5/5) 708:748 A subset were linked with key cancer pathways, and these peptides were shared across all of the leukemia patient samples tested (5/5). 28314751 2 35 theme neoantigens 239:249 arg1 identification 209:222 the identification 205:222 the identification of alternative neoantigens 205:249 Thus, the identification of alternative neoantigens is a pressing need. 28314751 2 35 theme neoantigens 239:249 arg1 need 265:268 a pressing need 254:268 a pressing need 254:268 Thus, the identification of alternative neoantigens is a pressing need. 28314751 8 36 theme cancer 1139:1144 arg1 immunotherapy 1146:1158 cancer immunotherapy 1139:1158 cancer immunotherapy 1139:1158 Therefore, these posttranslationally modified neoantigens provide logical targets for cancer immunotherapy. 28314751 2 37 theme alternative 227:237 arg1 neoantigens 239:249 alternative neoantigens 227:249 alternative neoantigens 227:249 Thus, the identification of alternative neoantigens is a pressing need. 28314751 4 38 theme same 533:536 arg1 residues 538:545 the same residues 529:545 the same residues 529:545 Thirteen of these peptides were also detected with disaccharide units on the same residues and two contain either mono- and/or di-methylated arginine residues. 28314751 3 39 theme MHC 292:294 arg1 antigens 323:330 36 MHC class I-associated peptide antigens 289:330 36 MHC class I-associated peptide antigens with O-linked β-N-acetylglucosamine (O-GlcNAc) modifications 289:391 Here, we identify 36 MHC class I-associated peptide antigens with O-linked β-N-acetylglucosamine (O-GlcNAc) modifications as candidate neoantigens, using three experimental approaches. 28314751 3 39 theme MHC 292:294 arg1 neoantigens 406:416 candidate neoantigens 396:416 candidate neoantigens 396:416 Here, we identify 36 MHC class I-associated peptide antigens with O-linked β-N-acetylglucosamine (O-GlcNAc) modifications as candidate neoantigens, using three experimental approaches. 28314751 4 40 theme peptides 474:481 arg1 Thirteen 456:463 Thirteen 456:463 Thirteen 456:463 Thirteen of these peptides were also detected with disaccharide units on the same residues and two contain either mono- and/or di-methylated arginine residues. 28314751 4 40 theme peptides 474:481 arg1 peptides 474:481 these peptides 468:481 these peptides 468:481 Thirteen of these peptides were also detected with disaccharide units on the same residues and two contain either mono- and/or di-methylated arginine residues. 28314751 6 41 theme memory 863:868 arg1 responses 877:885 multifunctional memory T-cell responses 847:885 multifunctional memory T-cell responses in healthy donors 847:903 Seven of the O-GlcNAc peptides were synthesized and five (71%) were shown to be associated with multifunctional memory T-cell responses in healthy donors. 28314751 3 42 theme class 296:300 arg1 antigens 323:330 36 MHC class I-associated peptide antigens 289:330 36 MHC class I-associated peptide antigens with O-linked β-N-acetylglucosamine (O-GlcNAc) modifications 289:391 Here, we identify 36 MHC class I-associated peptide antigens with O-linked β-N-acetylglucosamine (O-GlcNAc) modifications as candidate neoantigens, using three experimental approaches. 28314751 3 42 theme class 296:300 arg1 neoantigens 406:416 candidate neoantigens 396:416 candidate neoantigens 396:416 Here, we identify 36 MHC class I-associated peptide antigens with O-linked β-N-acetylglucosamine (O-GlcNAc) modifications as candidate neoantigens, using three experimental approaches. 28314751 6 43 theme healthy 890:896 arg1 donors 898:903 healthy donors 890:903 healthy donors 890:903 Seven of the O-GlcNAc peptides were synthesized and five (71%) were shown to be associated with multifunctional memory T-cell responses in healthy donors. 28314751 7 44 theme O-GlcNAc-specific 909:925 arg1 line 934:937 An O-GlcNAc-specific T-cell line 906:937 An O-GlcNAc-specific T-cell line 906:937 An O-GlcNAc-specific T-cell line specifically killed autologous cells pulsed with the modified peptide, but not the equivalent unmodified peptide. 28314751 5 45 dep tested 737:742 arg1 5/5 745:747 5/5 745:747 5/5 745:747 A subset were linked with key cancer pathways, and these peptides were shared across all of the leukemia patient samples tested (5/5). 28314751 5 45 dep tested 737:742 arg1 samples 729:735 the leukemia patient samples 708:735 the leukemia patient samples tested (5/5) 708:748 A subset were linked with key cancer pathways, and these peptides were shared across all of the leukemia patient samples tested (5/5). 28314751 6 46 from responses 877:885 arg1 donors 898:903 healthy donors 890:903 healthy donors 890:903 Seven of the O-GlcNAc peptides were synthesized and five (71%) were shown to be associated with multifunctional memory T-cell responses in healthy donors. 28314751 7 47 theme equivalent 1022:1031 arg1 peptide 1044:1050 the equivalent unmodified peptide 1018:1050 the equivalent unmodified peptide 1018:1050 An O-GlcNAc-specific T-cell line specifically killed autologous cells pulsed with the modified peptide, but not the equivalent unmodified peptide. 28314751 2 48 theme pressing 256:263 arg1 identification 209:222 the identification 205:222 the identification of alternative neoantigens 205:249 Thus, the identification of alternative neoantigens is a pressing need. 28314751 2 48 theme pressing 256:263 arg1 need 265:268 a pressing need 254:268 a pressing need 254:268 Thus, the identification of alternative neoantigens is a pressing need. 28314751 1 49 theme low 139:141 arg1 load 154:157 a low mutational load 137:157 a low mutational load 137:157 Leukemias are highly immunogenic, but they have a low mutational load, providing few mutated peptide targets. 28314751 3 50 with antigens 323:330 arg1 modifications 379:391 O-linked β-N-acetylglucosamine (O-GlcNAc) modifications 337:391 O-linked β-N-acetylglucosamine (O-GlcNAc) modifications 337:391 Here, we identify 36 MHC class I-associated peptide antigens with O-linked β-N-acetylglucosamine (O-GlcNAc) modifications as candidate neoantigens, using three experimental approaches. 28314751 7 51 theme modified 992:999 arg1 peptide 1001:1007 the modified peptide 988:1007 the modified peptide 988:1007 An O-GlcNAc-specific T-cell line specifically killed autologous cells pulsed with the modified peptide, but not the equivalent unmodified peptide. 28314751 1 52 theme mutational 143:152 arg1 load 154:157 a low mutational load 137:157 a low mutational load 137:157 Leukemias are highly immunogenic, but they have a low mutational load, providing few mutated peptide targets. 28314751 4 53 located detected 493:500 arg1 residues 538:545 the same residues 529:545 the same residues 529:545 Thirteen of these peptides were also detected with disaccharide units on the same residues and two contain either mono- and/or di-methylated arginine residues. 28314751 4 53 located detected 493:500 arg2 peptides 474:481 these peptides 468:481 these peptides 468:481 Thirteen of these peptides were also detected with disaccharide units on the same residues and two contain either mono- and/or di-methylated arginine residues. 28314751 4 53 located detected 493:500 arg2 Thirteen 456:463 Thirteen 456:463 Thirteen 456:463 Thirteen of these peptides were also detected with disaccharide units on the same residues and two contain either mono- and/or di-methylated arginine residues. 28238085 4 0 theme glutamate-induced 733:749 arg1 excitotoxicity 751:764 glutamate-induced excitotoxicity 733:764 glutamate-induced excitotoxicity 733:764 Here, we report that nNOS undergoes O-linked-β-N-acetylglucosamine (O-GlcNAc) modification via interacting with O-GlcNAc transferase, and the O-GlcNAcylation of nNOS remarkably increases during glutamate-induced excitotoxicity. 28238085 1 1 theme mortality 169:177 arg1 rates 160:164 extremely high rates 145:164 extremely high rates of mortality and disability 145:192 Ischemic stroke is a dominant health problem with extremely high rates of mortality and disability. 28238085 4 2 theme O-linked-β-N-acetylglucosamine 575:604 arg1 modification 617:628 O-linked-β-N-acetylglucosamine (O-GlcNAc) modification 575:628 O-linked-β-N-acetylglucosamine (O-GlcNAc) modification 575:628 Here, we report that nNOS undergoes O-linked-β-N-acetylglucosamine (O-GlcNAc) modification via interacting with O-GlcNAc transferase, and the O-GlcNAcylation of nNOS remarkably increases during glutamate-induced excitotoxicity. 28238085 5 3 from apoptosis 842:850 arg1 neurons 829:835 neurons 829:835 neurons from apoptosis 829:850 In addition, eliminating the O-GlcNAcylation of nNOS protects neurons from apoptosis during glutamate stimulation by decreasing the formation of nNOS-postsynaptic density protein 95 complexes. 28238085 2 4 theme vital 343:347 arg1 role 349:352 a vital role 341:352 a vital role 341:352 The main mechanism of neuronal injury after stroke is excitotoxicity, during which the activation of neuronal nitric oxide synthase (nNOS) exerts a vital role. 28238085 2 5 theme neuronal 296:303 arg1 nNOS 328:331 nNOS 328:331 nNOS 328:331 The main mechanism of neuronal injury after stroke is excitotoxicity, during which the activation of neuronal nitric oxide synthase (nNOS) exerts a vital role. 28238085 2 5 theme neuronal 296:303 arg1 synthase 318:325 neuronal nitric oxide synthase 296:325 neuronal nitric oxide synthase (nNOS) 296:332 The main mechanism of neuronal injury after stroke is excitotoxicity, during which the activation of neuronal nitric oxide synthase (nNOS) exerts a vital role. 28238085 1 6 theme dominant 116:123 arg1 problem 132:138 a dominant health problem 114:138 a dominant health problem with extremely high rates of mortality and disability 114:192 Ischemic stroke is a dominant health problem with extremely high rates of mortality and disability. 28238085 1 6 theme dominant 116:123 arg1 stroke 104:109 Ischemic stroke 95:109 Ischemic stroke 95:109 Ischemic stroke is a dominant health problem with extremely high rates of mortality and disability. 28238085 5 7 theme eliminating 780:790 arg1 O-GlcNAcylation 796:810 the O-GlcNAcylation 792:810 eliminating the O-GlcNAcylation of nNOS 780:818 In addition, eliminating the O-GlcNAcylation of nNOS protects neurons from apoptosis during glutamate stimulation by decreasing the formation of nNOS-postsynaptic density protein 95 complexes. 28238085 4 8 theme O-GlcNAc 607:614 arg1 modification 617:628 O-linked-β-N-acetylglucosamine (O-GlcNAc) modification 575:628 O-linked-β-N-acetylglucosamine (O-GlcNAc) modification 575:628 Here, we report that nNOS undergoes O-linked-β-N-acetylglucosamine (O-GlcNAc) modification via interacting with O-GlcNAc transferase, and the O-GlcNAcylation of nNOS remarkably increases during glutamate-induced excitotoxicity. 28238085 4 9 theme O-GlcNAc 651:658 arg1 transferase 660:670 O-GlcNAc transferase 651:670 O-GlcNAc transferase 651:670 Here, we report that nNOS undergoes O-linked-β-N-acetylglucosamine (O-GlcNAc) modification via interacting with O-GlcNAc transferase, and the O-GlcNAcylation of nNOS remarkably increases during glutamate-induced excitotoxicity. 28238085 5 10 theme complexes 949:957 arg1 formation 899:907 the formation 895:907 the formation of nNOS-postsynaptic density protein 95 complexes 895:957 In addition, eliminating the O-GlcNAcylation of nNOS protects neurons from apoptosis during glutamate stimulation by decreasing the formation of nNOS-postsynaptic density protein 95 complexes. 28238085 3 11 theme severe 433:438 arg1 effects 452:458 severe undesirable effects 433:458 severe undesirable effects 433:458 However, directly blocking N-methyl-D-aspartate receptors or nNOS can lead to severe undesirable effects since they have crucial physiological functions in the central nervous system. 28238085 3 12 theme N-methyl-D-aspartate 382:401 arg1 receptors 403:411 N-methyl-D-aspartate receptors 382:411 N-methyl-D-aspartate receptors 382:411 However, directly blocking N-methyl-D-aspartate receptors or nNOS can lead to severe undesirable effects since they have crucial physiological functions in the central nervous system. 28238085 1 13 theme disability 183:192 arg1 rates 160:164 extremely high rates 145:164 extremely high rates of mortality and disability 145:192 Ischemic stroke is a dominant health problem with extremely high rates of mortality and disability. 28238085 4 14 theme nNOS 700:703 arg1 O-GlcNAcylation 681:695 the O-GlcNAcylation 677:695 the O-GlcNAcylation of nNOS 677:703 Here, we report that nNOS undergoes O-linked-β-N-acetylglucosamine (O-GlcNAc) modification via interacting with O-GlcNAc transferase, and the O-GlcNAcylation of nNOS remarkably increases during glutamate-induced excitotoxicity. 28238085 0 15 theme O-GlcNAc 0:7 arg1 Glycosylation 9:21 O-GlcNAc Glycosylation 0:21 O-GlcNAc Glycosylation of nNOS 0:29 O-GlcNAc Glycosylation of nNOS Promotes Neuronal Apoptosis Following Glutamate Excitotoxicity. 28238085 6 16 theme neuronal 1044:1051 arg1 apoptosis 1053:1061 neuronal apoptosis 1044:1061 neuronal apoptosis 1044:1061 Taken together, our data suggest a novel function of the O-GlcNAcylation of nNOS in neuronal apoptosis during glutamate excitotoxicity, suggesting a novel therapy strategy for ischemic stroke. 28238085 1 17 with problem 132:138 arg1 rates 160:164 extremely high rates 145:164 extremely high rates of mortality and disability 145:192 Ischemic stroke is a dominant health problem with extremely high rates of mortality and disability. 28238085 2 18 theme synthase 318:325 arg1 activation 282:291 the activation 278:291 the activation of neuronal nitric oxide synthase (nNOS) 278:332 The main mechanism of neuronal injury after stroke is excitotoxicity, during which the activation of neuronal nitric oxide synthase (nNOS) exerts a vital role. 28238085 0 19 theme nNOS 26:29 arg1 Glycosylation 9:21 O-GlcNAc Glycosylation 0:21 O-GlcNAc Glycosylation of nNOS 0:29 O-GlcNAc Glycosylation of nNOS Promotes Neuronal Apoptosis Following Glutamate Excitotoxicity. 28238085 2 20 theme oxide 312:316 arg1 nNOS 328:331 nNOS 328:331 nNOS 328:331 The main mechanism of neuronal injury after stroke is excitotoxicity, during which the activation of neuronal nitric oxide synthase (nNOS) exerts a vital role. 28238085 2 20 theme oxide 312:316 arg1 synthase 318:325 neuronal nitric oxide synthase 296:325 neuronal nitric oxide synthase (nNOS) 296:332 The main mechanism of neuronal injury after stroke is excitotoxicity, during which the activation of neuronal nitric oxide synthase (nNOS) exerts a vital role. 28238085 6 21 theme ischemic 1136:1143 arg1 stroke 1145:1150 ischemic stroke 1136:1150 ischemic stroke 1136:1150 Taken together, our data suggest a novel function of the O-GlcNAcylation of nNOS in neuronal apoptosis during glutamate excitotoxicity, suggesting a novel therapy strategy for ischemic stroke. 28238085 6 22 theme nNOS 1036:1039 arg1 O-GlcNAcylation 1017:1031 the O-GlcNAcylation 1013:1031 the O-GlcNAcylation of nNOS 1013:1039 Taken together, our data suggest a novel function of the O-GlcNAcylation of nNOS in neuronal apoptosis during glutamate excitotoxicity, suggesting a novel therapy strategy for ischemic stroke. 28238085 2 23 theme nitric 305:310 arg1 nNOS 328:331 nNOS 328:331 nNOS 328:331 The main mechanism of neuronal injury after stroke is excitotoxicity, during which the activation of neuronal nitric oxide synthase (nNOS) exerts a vital role. 28238085 2 23 theme nitric 305:310 arg1 synthase 318:325 neuronal nitric oxide synthase 296:325 neuronal nitric oxide synthase (nNOS) 296:332 The main mechanism of neuronal injury after stroke is excitotoxicity, during which the activation of neuronal nitric oxide synthase (nNOS) exerts a vital role. 28238085 3 24 theme nervous 523:529 arg1 system 531:536 the central nervous system 511:536 the central nervous system 511:536 However, directly blocking N-methyl-D-aspartate receptors or nNOS can lead to severe undesirable effects since they have crucial physiological functions in the central nervous system. 28238085 0 25 theme Neuronal 40:47 arg1 Apoptosis 49:57 Neuronal Apoptosis 40:57 Neuronal Apoptosis 40:57 O-GlcNAc Glycosylation of nNOS Promotes Neuronal Apoptosis Following Glutamate Excitotoxicity. 28238085 5 26 theme nNOS-postsynaptic 912:928 arg1 complexes 949:957 nNOS-postsynaptic density protein 95 complexes 912:957 nNOS-postsynaptic density protein 95 complexes 912:957 In addition, eliminating the O-GlcNAcylation of nNOS protects neurons from apoptosis during glutamate stimulation by decreasing the formation of nNOS-postsynaptic density protein 95 complexes. 28238085 5 27 theme protein 938:944 arg1 complexes 949:957 nNOS-postsynaptic density protein 95 complexes 912:957 nNOS-postsynaptic density protein 95 complexes 912:957 In addition, eliminating the O-GlcNAcylation of nNOS protects neurons from apoptosis during glutamate stimulation by decreasing the formation of nNOS-postsynaptic density protein 95 complexes. 28238085 6 28 theme O-GlcNAcylation 1017:1031 arg1 function 1001:1008 a novel function 993:1008 a novel function of the O-GlcNAcylation of nNOS in neuronal apoptosis 993:1061 Taken together, our data suggest a novel function of the O-GlcNAcylation of nNOS in neuronal apoptosis during glutamate excitotoxicity, suggesting a novel therapy strategy for ischemic stroke. 28238085 6 29 theme glutamate 1070:1078 arg1 excitotoxicity 1080:1093 glutamate excitotoxicity 1070:1093 glutamate excitotoxicity 1070:1093 Taken together, our data suggest a novel function of the O-GlcNAcylation of nNOS in neuronal apoptosis during glutamate excitotoxicity, suggesting a novel therapy strategy for ischemic stroke. 28238085 3 30 contain have 471:474 arg1 they 466:469 they 466:469 they 466:469 However, directly blocking N-methyl-D-aspartate receptors or nNOS can lead to severe undesirable effects since they have crucial physiological functions in the central nervous system. 28238085 3 30 contain have 471:474 arg2 functions 498:506 crucial physiological functions 476:506 crucial physiological functions 476:506 However, directly blocking N-methyl-D-aspartate receptors or nNOS can lead to severe undesirable effects since they have crucial physiological functions in the central nervous system. 28238085 0 31 gly Glycosylation 9:21 arg1 nNOS 26:29 nNOS 26:29 nNOS 26:29 O-GlcNAc Glycosylation of nNOS Promotes Neuronal Apoptosis Following Glutamate Excitotoxicity. 28238085 5 32 theme density 930:936 arg1 complexes 949:957 nNOS-postsynaptic density protein 95 complexes 912:957 nNOS-postsynaptic density protein 95 complexes 912:957 In addition, eliminating the O-GlcNAcylation of nNOS protects neurons from apoptosis during glutamate stimulation by decreasing the formation of nNOS-postsynaptic density protein 95 complexes. 28238085 6 33 theme therapy 1115:1121 arg1 strategy 1123:1130 a novel therapy strategy 1107:1130 a novel therapy strategy for ischemic stroke 1107:1150 Taken together, our data suggest a novel function of the O-GlcNAcylation of nNOS in neuronal apoptosis during glutamate excitotoxicity, suggesting a novel therapy strategy for ischemic stroke. 28238085 5 34 theme nNOS 815:818 arg1 O-GlcNAcylation 796:810 the O-GlcNAcylation 792:810 eliminating the O-GlcNAcylation of nNOS 780:818 In addition, eliminating the O-GlcNAcylation of nNOS protects neurons from apoptosis during glutamate stimulation by decreasing the formation of nNOS-postsynaptic density protein 95 complexes. 28238085 1 35 theme health 125:130 arg1 problem 132:138 a dominant health problem 114:138 a dominant health problem with extremely high rates of mortality and disability 114:192 Ischemic stroke is a dominant health problem with extremely high rates of mortality and disability. 28238085 1 35 theme health 125:130 arg1 stroke 104:109 Ischemic stroke 95:109 Ischemic stroke 95:109 Ischemic stroke is a dominant health problem with extremely high rates of mortality and disability. 28238085 5 36 theme glutamate 859:867 arg1 stimulation 869:879 glutamate stimulation 859:879 glutamate stimulation 859:879 In addition, eliminating the O-GlcNAcylation of nNOS protects neurons from apoptosis during glutamate stimulation by decreasing the formation of nNOS-postsynaptic density protein 95 complexes. 28238085 6 37 from function 1001:1008 arg1 apoptosis 1053:1061 neuronal apoptosis 1044:1061 neuronal apoptosis 1044:1061 Taken together, our data suggest a novel function of the O-GlcNAcylation of nNOS in neuronal apoptosis during glutamate excitotoxicity, suggesting a novel therapy strategy for ischemic stroke. 28238085 2 38 theme neuronal 217:224 arg1 injury 226:231 neuronal injury 217:231 neuronal injury 217:231 The main mechanism of neuronal injury after stroke is excitotoxicity, during which the activation of neuronal nitric oxide synthase (nNOS) exerts a vital role. 28238085 2 39 theme injury 226:231 arg1 mechanism 204:212 The main mechanism 195:212 The main mechanism of neuronal injury after stroke 195:244 The main mechanism of neuronal injury after stroke is excitotoxicity, during which the activation of neuronal nitric oxide synthase (nNOS) exerts a vital role. 28238085 2 39 theme injury 226:231 arg1 excitotoxicity 249:262 excitotoxicity 249:262 excitotoxicity 249:262 The main mechanism of neuronal injury after stroke is excitotoxicity, during which the activation of neuronal nitric oxide synthase (nNOS) exerts a vital role. 28238085 3 40 theme central 515:521 arg1 system 531:536 the central nervous system 511:536 the central nervous system 511:536 However, directly blocking N-methyl-D-aspartate receptors or nNOS can lead to severe undesirable effects since they have crucial physiological functions in the central nervous system. 28238085 3 41 theme crucial 476:482 arg1 functions 498:506 crucial physiological functions 476:506 crucial physiological functions 476:506 However, directly blocking N-methyl-D-aspartate receptors or nNOS can lead to severe undesirable effects since they have crucial physiological functions in the central nervous system. 28238085 6 42 theme novel 1109:1113 arg1 strategy 1123:1130 a novel therapy strategy 1107:1130 a novel therapy strategy for ischemic stroke 1107:1150 Taken together, our data suggest a novel function of the O-GlcNAcylation of nNOS in neuronal apoptosis during glutamate excitotoxicity, suggesting a novel therapy strategy for ischemic stroke. 28238085 1 43 theme Ischemic 95:102 arg1 problem 132:138 a dominant health problem 114:138 a dominant health problem with extremely high rates of mortality and disability 114:192 Ischemic stroke is a dominant health problem with extremely high rates of mortality and disability. 28238085 1 43 theme Ischemic 95:102 arg1 stroke 104:109 Ischemic stroke 95:109 Ischemic stroke 95:109 Ischemic stroke is a dominant health problem with extremely high rates of mortality and disability. 28238085 3 44 theme physiological 484:496 arg1 functions 498:506 crucial physiological functions 476:506 crucial physiological functions 476:506 However, directly blocking N-methyl-D-aspartate receptors or nNOS can lead to severe undesirable effects since they have crucial physiological functions in the central nervous system. 28238085 2 45 theme main 199:202 arg1 mechanism 204:212 The main mechanism 195:212 The main mechanism of neuronal injury after stroke 195:244 The main mechanism of neuronal injury after stroke is excitotoxicity, during which the activation of neuronal nitric oxide synthase (nNOS) exerts a vital role. 28238085 2 45 theme main 199:202 arg1 excitotoxicity 249:262 excitotoxicity 249:262 excitotoxicity 249:262 The main mechanism of neuronal injury after stroke is excitotoxicity, during which the activation of neuronal nitric oxide synthase (nNOS) exerts a vital role. 28238085 1 46 theme high 155:158 arg1 rates 160:164 extremely high rates 145:164 extremely high rates of mortality and disability 145:192 Ischemic stroke is a dominant health problem with extremely high rates of mortality and disability. 28238085 3 47 theme undesirable 440:450 arg1 effects 452:458 severe undesirable effects 433:458 severe undesirable effects 433:458 However, directly blocking N-methyl-D-aspartate receptors or nNOS can lead to severe undesirable effects since they have crucial physiological functions in the central nervous system. 28238085 0 48 theme Glutamate 69:77 arg1 Excitotoxicity 79:92 Glutamate Excitotoxicity 69:92 Glutamate Excitotoxicity 69:92 O-GlcNAc Glycosylation of nNOS Promotes Neuronal Apoptosis Following Glutamate Excitotoxicity. 28238085 6 49 theme novel 995:999 arg1 function 1001:1008 a novel function 993:1008 a novel function of the O-GlcNAcylation of nNOS in neuronal apoptosis 993:1061 Taken together, our data suggest a novel function of the O-GlcNAcylation of nNOS in neuronal apoptosis during glutamate excitotoxicity, suggesting a novel therapy strategy for ischemic stroke. 28190768 6 0 theme serine-specific 711:725 arg1 ADPr 727:730 serine-specific ADPr 711:730 serine-specific ADPr of histones and PARP-1 itself 711:760 Moreover, adding HPF1 to in vitro PARP-1/PARP-2 reactions is necessary and sufficient for serine-specific ADPr of histones and PARP-1 itself. 28190768 7 1 theme PARP-1 817:822 arg1 domain 841:846 the PARP-1 automodification domain 813:846 the PARP-1 automodification domain 813:846 Three endogenous serine ADPr sites are located on the PARP-1 automodification domain. 28190768 9 2 theme PARP-1/PARP-2-dependent 1049:1071 arg1 processes 1073:1081 PARP-1/PARP-2-dependent processes 1049:1081 PARP-1/PARP-2-dependent processes that govern genome stability 1049:1110 We propose that O-linked protein ADPr is the key signal in PARP-1/PARP-2-dependent processes that govern genome stability. 28190768 8 3 from hundreds 907:914 arg1 identification 857:870 Further identification 849:870 Further identification of serine ADPr on HMG proteins and hundreds of other targets 849:931 Further identification of serine ADPr on HMG proteins and hundreds of other targets indicates that serine ADPr is a widespread modification. 28190768 8 4 theme widespread 965:974 arg1 ADPr 955:958 serine ADPr 948:958 serine ADPr 948:958 Further identification of serine ADPr on HMG proteins and hundreds of other targets indicates that serine ADPr is a widespread modification. 28190768 8 4 theme widespread 965:974 arg1 modification 976:987 a widespread modification 963:987 a widespread modification 963:987 Further identification of serine ADPr on HMG proteins and hundreds of other targets indicates that serine ADPr is a widespread modification. 28190768 3 5 theme serine 359:364 arg1 modification 366:377 this serine modification 354:377 this serine modification 354:377 However, the biochemical basis underlying this serine modification remained unknown. 28190768 8 6 theme other 919:923 arg1 targets 925:931 other targets 919:931 other targets 919:931 Further identification of serine ADPr on HMG proteins and hundreds of other targets indicates that serine ADPr is a widespread modification. 28190768 1 7 from acids 157:161 arg1 proteins 166:173 proteins 166:173 proteins 166:173 ADP-ribosylation (ADPr) regulates important patho-physiological processes through its attachment to different amino acids in proteins. 28190768 8 8 theme ADPr 882:885 arg1 identification 857:870 Further identification 849:870 Further identification of serine ADPr on HMG proteins and hundreds of other targets 849:931 Further identification of serine ADPr on HMG proteins and hundreds of other targets indicates that serine ADPr is a widespread modification. 28190768 9 9 from signal 1039:1044 arg1 processes 1073:1081 PARP-1/PARP-2-dependent processes 1049:1081 PARP-1/PARP-2-dependent processes that govern genome stability 1049:1110 We propose that O-linked protein ADPr is the key signal in PARP-1/PARP-2-dependent processes that govern genome stability. 28190768 8 10 theme serine 875:880 arg1 ADPr 882:885 serine ADPr 875:885 serine ADPr on HMG proteins and hundreds of other targets 875:931 Further identification of serine ADPr on HMG proteins and hundreds of other targets indicates that serine ADPr is a widespread modification. 28190768 1 11 theme important 75:83 arg1 processes 105:113 important patho-physiological processes 75:113 important patho-physiological processes 75:113 ADP-ribosylation (ADPr) regulates important patho-physiological processes through its attachment to different amino acids in proteins. 28190768 8 12 theme HMG 890:892 arg1 proteins 894:901 HMG proteins 890:901 HMG proteins 890:901 Further identification of serine ADPr on HMG proteins and hundreds of other targets indicates that serine ADPr is a widespread modification. 28190768 5 13 theme serine 571:576 arg1 ADPr 578:581 serine ADPr 571:581 serine ADPr 571:581 Quantitative proteomics revealed that serine ADPr does not occur in cells lacking HPF1. 28190768 1 14 theme patho-physiological 85:103 arg1 processes 105:113 important patho-physiological processes 75:113 important patho-physiological processes 75:113 ADP-ribosylation (ADPr) regulates important patho-physiological processes through its attachment to different amino acids in proteins. 28190768 0 15 theme Serine 0:5 arg1 ADP-Ribosylation 7:22 Serine ADP-Ribosylation 0:22 Serine ADP-Ribosylation 0:22 Serine ADP-Ribosylation Depends on HPF1. 28190768 7 16 located located 802:808 arg1 domain 841:846 the PARP-1 automodification domain 813:846 the PARP-1 automodification domain 813:846 Three endogenous serine ADPr sites are located on the PARP-1 automodification domain. 28190768 7 16 located located 802:808 arg2 sites 792:796 Three endogenous serine ADPr sites 763:796 Three endogenous serine ADPr sites 763:796 Three endogenous serine ADPr sites are located on the PARP-1 automodification domain. 28190768 7 17 theme automodification 824:839 arg1 domain 841:846 the PARP-1 automodification domain 813:846 the PARP-1 automodification domain 813:846 Three endogenous serine ADPr sites are located on the PARP-1 automodification domain. 28190768 7 18 theme ADPr 787:790 arg1 sites 792:796 Three endogenous serine ADPr sites 763:796 Three endogenous serine ADPr sites 763:796 Three endogenous serine ADPr sites are located on the PARP-1 automodification domain. 28190768 2 19 theme damage 295:300 arg1 response 302:309 the DNA damage response 287:309 the DNA damage response 287:309 Recently, by precision mapping on all possible amino acid residues, we identified histone serine ADPr marks in the DNA damage response. 28190768 8 20 from identification 857:870 arg1 hundreds 907:914 hundreds 907:914 hundreds of other targets 907:931 Further identification of serine ADPr on HMG proteins and hundreds of other targets indicates that serine ADPr is a widespread modification. 28190768 8 20 from identification 857:870 arg1 proteins 894:901 HMG proteins 890:901 HMG proteins 890:901 Further identification of serine ADPr on HMG proteins and hundreds of other targets indicates that serine ADPr is a widespread modification. 28190768 2 21 theme precision 189:197 arg1 mapping 199:205 precision mapping 189:205 precision mapping on all possible amino acid residues 189:241 Recently, by precision mapping on all possible amino acid residues, we identified histone serine ADPr marks in the DNA damage response. 28190768 2 22 theme DNA 291:293 arg1 damage 295:300 DNA damage 291:300 the DNA damage response 287:309 Recently, by precision mapping on all possible amino acid residues, we identified histone serine ADPr marks in the DNA damage response. 28190768 6 23 theme PARP-1/PARP-2 655:667 arg1 reactions 669:677 in vitro PARP-1/PARP-2 reactions 646:677 in vitro PARP-1/PARP-2 reactions 646:677 Moreover, adding HPF1 to in vitro PARP-1/PARP-2 reactions is necessary and sufficient for serine-specific ADPr of histones and PARP-1 itself. 28190768 8 24 from ADPr 882:885 arg1 hundreds 907:914 hundreds 907:914 hundreds of other targets 907:931 Further identification of serine ADPr on HMG proteins and hundreds of other targets indicates that serine ADPr is a widespread modification. 28190768 8 24 from ADPr 882:885 arg1 proteins 894:901 HMG proteins 890:901 HMG proteins 890:901 Further identification of serine ADPr on HMG proteins and hundreds of other targets indicates that serine ADPr is a widespread modification. 28190768 9 25 link O-linked 1006:1013 arg1 ADPr 1023:1026 O-linked protein ADPr 1006:1026 O-linked protein ADPr 1006:1026 We propose that O-linked protein ADPr is the key signal in PARP-1/PARP-2-dependent processes that govern genome stability. 28190768 9 25 link O-linked 1006:1013 arg1 signal 1039:1044 the key signal 1031:1044 the key signal in PARP-1/PARP-2-dependent processes that govern genome stability 1031:1110 We propose that O-linked protein ADPr is the key signal in PARP-1/PARP-2-dependent processes that govern genome stability. 28190768 6 26 theme in vitro 646:653 arg1 reactions 669:677 in vitro PARP-1/PARP-2 reactions 646:677 in vitro PARP-1/PARP-2 reactions 646:677 Moreover, adding HPF1 to in vitro PARP-1/PARP-2 reactions is necessary and sufficient for serine-specific ADPr of histones and PARP-1 itself. 28190768 7 27 theme serine 780:785 arg1 sites 792:796 Three endogenous serine ADPr sites 763:796 Three endogenous serine ADPr sites 763:796 Three endogenous serine ADPr sites are located on the PARP-1 automodification domain. 28190768 4 28 theme PARylation 462:471 arg1 factor 473:478 histone PARylation factor 1 454:480 histone PARylation factor 1 (HPF1) 454:487 Here we report that serine ADPr is strictly dependent on histone PARylation factor 1 (HPF1), a recently identified regulator of PARP-1. 28190768 4 28 theme PARylation 462:471 arg1 HPF1 483:486 HPF1 483:486 HPF1 483:486 Here we report that serine ADPr is strictly dependent on histone PARylation factor 1 (HPF1), a recently identified regulator of PARP-1. 28190768 4 28 theme PARylation 462:471 arg1 regulator 512:520 a recently identified regulator 490:520 a recently identified regulator of PARP-1 490:530 Here we report that serine ADPr is strictly dependent on histone PARylation factor 1 (HPF1), a recently identified regulator of PARP-1. 28190768 8 29 theme targets 925:931 arg1 hundreds 907:914 hundreds 907:914 hundreds of other targets 907:931 Further identification of serine ADPr on HMG proteins and hundreds of other targets indicates that serine ADPr is a widespread modification. 28190768 8 29 theme targets 925:931 arg1 proteins 894:901 HMG proteins 890:901 HMG proteins 890:901 Further identification of serine ADPr on HMG proteins and hundreds of other targets indicates that serine ADPr is a widespread modification. 28190768 9 30 theme O-linked 1006:1013 arg1 ADPr 1023:1026 O-linked protein ADPr 1006:1026 O-linked protein ADPr 1006:1026 We propose that O-linked protein ADPr is the key signal in PARP-1/PARP-2-dependent processes that govern genome stability. 28190768 9 30 theme O-linked 1006:1013 arg1 signal 1039:1044 the key signal 1031:1044 the key signal in PARP-1/PARP-2-dependent processes that govern genome stability 1031:1110 We propose that O-linked protein ADPr is the key signal in PARP-1/PARP-2-dependent processes that govern genome stability. 28190768 4 31 theme identified 501:510 arg1 factor 473:478 histone PARylation factor 1 454:480 histone PARylation factor 1 (HPF1) 454:487 Here we report that serine ADPr is strictly dependent on histone PARylation factor 1 (HPF1), a recently identified regulator of PARP-1. 28190768 4 31 theme identified 501:510 arg1 regulator 512:520 a recently identified regulator 490:520 a recently identified regulator of PARP-1 490:530 Here we report that serine ADPr is strictly dependent on histone PARylation factor 1 (HPF1), a recently identified regulator of PARP-1. 28190768 4 32 theme histone 454:460 arg1 factor 473:478 histone PARylation factor 1 454:480 histone PARylation factor 1 (HPF1) 454:487 Here we report that serine ADPr is strictly dependent on histone PARylation factor 1 (HPF1), a recently identified regulator of PARP-1. 28190768 4 32 theme histone 454:460 arg1 HPF1 483:486 HPF1 483:486 HPF1 483:486 Here we report that serine ADPr is strictly dependent on histone PARylation factor 1 (HPF1), a recently identified regulator of PARP-1. 28190768 4 32 theme histone 454:460 arg1 regulator 512:520 a recently identified regulator 490:520 a recently identified regulator of PARP-1 490:530 Here we report that serine ADPr is strictly dependent on histone PARylation factor 1 (HPF1), a recently identified regulator of PARP-1. 28190768 2 33 theme acid 229:232 arg1 residues 234:241 all possible amino acid residues 210:241 all possible amino acid residues 210:241 Recently, by precision mapping on all possible amino acid residues, we identified histone serine ADPr marks in the DNA damage response. 28190768 5 34 theme Quantitative 533:544 arg1 proteomics 546:555 Quantitative proteomics 533:555 Quantitative proteomics 533:555 Quantitative proteomics revealed that serine ADPr does not occur in cells lacking HPF1. 28190768 9 35 theme protein 1015:1021 arg1 ADPr 1023:1026 O-linked protein ADPr 1006:1026 O-linked protein ADPr 1006:1026 We propose that O-linked protein ADPr is the key signal in PARP-1/PARP-2-dependent processes that govern genome stability. 28190768 9 35 theme protein 1015:1021 arg1 signal 1039:1044 the key signal 1031:1044 the key signal in PARP-1/PARP-2-dependent processes that govern genome stability 1031:1110 We propose that O-linked protein ADPr is the key signal in PARP-1/PARP-2-dependent processes that govern genome stability. 28190768 4 36 theme PARP-1 525:530 arg1 factor 473:478 histone PARylation factor 1 454:480 histone PARylation factor 1 (HPF1) 454:487 Here we report that serine ADPr is strictly dependent on histone PARylation factor 1 (HPF1), a recently identified regulator of PARP-1. 28190768 4 36 theme PARP-1 525:530 arg1 regulator 512:520 a recently identified regulator 490:520 a recently identified regulator of PARP-1 490:530 Here we report that serine ADPr is strictly dependent on histone PARylation factor 1 (HPF1), a recently identified regulator of PARP-1. 28190768 2 37 theme possible 214:221 arg1 residues 234:241 all possible amino acid residues 210:241 all possible amino acid residues 210:241 Recently, by precision mapping on all possible amino acid residues, we identified histone serine ADPr marks in the DNA damage response. 28190768 2 38 theme amino 223:227 arg1 residues 234:241 all possible amino acid residues 210:241 all possible amino acid residues 210:241 Recently, by precision mapping on all possible amino acid residues, we identified histone serine ADPr marks in the DNA damage response. 28190768 6 39 theme PARP-1 748:753 arg1 ADPr 727:730 serine-specific ADPr 711:730 serine-specific ADPr of histones and PARP-1 itself 711:760 Moreover, adding HPF1 to in vitro PARP-1/PARP-2 reactions is necessary and sufficient for serine-specific ADPr of histones and PARP-1 itself. 28190768 7 40 theme endogenous 769:778 arg1 sites 792:796 Three endogenous serine ADPr sites 763:796 Three endogenous serine ADPr sites 763:796 Three endogenous serine ADPr sites are located on the PARP-1 automodification domain. 28190768 4 41 theme serine 417:422 arg1 ADPr 424:427 serine ADPr 417:427 serine ADPr 417:427 Here we report that serine ADPr is strictly dependent on histone PARylation factor 1 (HPF1), a recently identified regulator of PARP-1. 28190768 2 42 theme serine 266:271 arg1 ADPr 273:276 histone serine ADPr marks 258:282 histone serine ADPr marks in the DNA damage response 258:309 Recently, by precision mapping on all possible amino acid residues, we identified histone serine ADPr marks in the DNA damage response. 28190768 1 43 theme different 141:149 arg1 acids 157:161 different amino acids 141:161 different amino acids in proteins 141:173 ADP-ribosylation (ADPr) regulates important patho-physiological processes through its attachment to different amino acids in proteins. 28190768 2 44 from ADPr 273:276 arg1 response 302:309 the DNA damage response 287:309 the DNA damage response 287:309 Recently, by precision mapping on all possible amino acid residues, we identified histone serine ADPr marks in the DNA damage response. 28190768 2 45 theme histone 258:264 arg1 ADPr 273:276 histone serine ADPr marks 258:282 histone serine ADPr marks in the DNA damage response 258:309 Recently, by precision mapping on all possible amino acid residues, we identified histone serine ADPr marks in the DNA damage response. 28190768 6 46 theme histones 735:742 arg1 ADPr 727:730 serine-specific ADPr 711:730 serine-specific ADPr of histones and PARP-1 itself 711:760 Moreover, adding HPF1 to in vitro PARP-1/PARP-2 reactions is necessary and sufficient for serine-specific ADPr of histones and PARP-1 itself. 28190768 1 47 theme amino 151:155 arg1 acids 157:161 different amino acids 141:161 different amino acids in proteins 141:173 ADP-ribosylation (ADPr) regulates important patho-physiological processes through its attachment to different amino acids in proteins. 28190768 6 48 theme adding 631:636 arg1 HPF1 638:641 adding HPF1 631:641 adding HPF1 to in vitro PARP-1/PARP-2 reactions 631:677 Moreover, adding HPF1 to in vitro PARP-1/PARP-2 reactions is necessary and sufficient for serine-specific ADPr of histones and PARP-1 itself. 28190768 9 49 theme genome 1095:1100 arg1 stability 1102:1110 genome stability 1095:1110 genome stability 1095:1110 We propose that O-linked protein ADPr is the key signal in PARP-1/PARP-2-dependent processes that govern genome stability. 28190768 8 50 theme serine 948:953 arg1 ADPr 955:958 serine ADPr 948:958 serine ADPr 948:958 Further identification of serine ADPr on HMG proteins and hundreds of other targets indicates that serine ADPr is a widespread modification. 28190768 8 50 theme serine 948:953 arg1 modification 976:987 a widespread modification 963:987 a widespread modification 963:987 Further identification of serine ADPr on HMG proteins and hundreds of other targets indicates that serine ADPr is a widespread modification. 28190768 9 51 theme key 1035:1037 arg1 ADPr 1023:1026 O-linked protein ADPr 1006:1026 O-linked protein ADPr 1006:1026 We propose that O-linked protein ADPr is the key signal in PARP-1/PARP-2-dependent processes that govern genome stability. 28190768 9 51 theme key 1035:1037 arg1 signal 1039:1044 the key signal 1031:1044 the key signal in PARP-1/PARP-2-dependent processes that govern genome stability 1031:1110 We propose that O-linked protein ADPr is the key signal in PARP-1/PARP-2-dependent processes that govern genome stability. 28190768 3 52 theme biochemical 325:335 arg1 basis 337:341 the biochemical basis 321:341 the biochemical basis underlying this serine modification 321:377 However, the biochemical basis underlying this serine modification remained unknown. 28190768 8 53 from proteins 894:901 arg1 identification 857:870 Further identification 849:870 Further identification of serine ADPr on HMG proteins and hundreds of other targets 849:931 Further identification of serine ADPr on HMG proteins and hundreds of other targets indicates that serine ADPr is a widespread modification. 28190768 2 54 dep ADPr 273:276 arg1 marks 278:282 marks 278:282 marks 278:282 Recently, by precision mapping on all possible amino acid residues, we identified histone serine ADPr marks in the DNA damage response. 28190768 8 55 theme Further 849:855 arg1 identification 857:870 Further identification 849:870 Further identification of serine ADPr on HMG proteins and hundreds of other targets 849:931 Further identification of serine ADPr on HMG proteins and hundreds of other targets indicates that serine ADPr is a widespread modification. 28190768 2 56 from mapping 199:205 arg1 residues 234:241 all possible amino acid residues 210:241 all possible amino acid residues 210:241 Recently, by precision mapping on all possible amino acid residues, we identified histone serine ADPr marks in the DNA damage response. 28361969 0 0 theme diagnostic 61:70 arg1 protein 36:42 a novel mucin-like membrane protein 8:42 a novel mucin-like membrane protein that serves as a diagnostic and therapeutic target for malignant mesothelioma 8:120 HEG1 is a novel mucin-like membrane protein that serves as a diagnostic and therapeutic target for malignant mesothelioma. 28361969 0 0 theme diagnostic 61:70 arg1 target 88:93 a diagnostic and therapeutic target 59:93 a diagnostic and therapeutic target for malignant mesothelioma 59:120 HEG1 is a novel mucin-like membrane protein that serves as a diagnostic and therapeutic target for malignant mesothelioma. 28361969 5 1 theme accurate 668:675 arg1 discrimination 677:690 This accurate discrimination 663:690 This accurate discrimination by SKM9-2 663:700 This accurate discrimination by SKM9-2 was due to the recognition of a sialylated O-linked glycan with HEG1 peptide. 28361969 5 2 link O-linked 745:752 arg1 glycan 754:759 a sialylated O-linked glycan 732:759 a sialylated O-linked glycan with HEG1 peptide 732:777 This accurate discrimination by SKM9-2 was due to the recognition of a sialylated O-linked glycan with HEG1 peptide. 28361969 6 3 theme worthwhile 941:950 arg1 target 952:957 a worthwhile target 939:957 a worthwhile target for function-inhibition drugs 939:987 We also found that gene silencing of HEG1 significantly suppressed the survival and proliferation of mesothelioma cells; this result suggests that HEG1 may be a worthwhile target for function-inhibition drugs. 28361969 6 3 theme worthwhile 941:950 arg1 HEG1 927:930 HEG1 927:930 HEG1 927:930 We also found that gene silencing of HEG1 significantly suppressed the survival and proliferation of mesothelioma cells; this result suggests that HEG1 may be a worthwhile target for function-inhibition drugs. 28361969 2 4 theme mucin-like 321:330 arg1 marker 412:417 a highly specific marker 394:417 a highly specific marker for MM 394:424 Here, we show that a novel mucin-like membrane protein, sialylated protein HEG homolog 1 (HEG1), is a highly specific marker for MM. 28361969 2 4 theme mucin-like 321:330 arg1 homolog 373:379 sialylated protein HEG homolog 1 350:381 sialylated protein HEG homolog 1 (HEG1) 350:388 Here, we show that a novel mucin-like membrane protein, sialylated protein HEG homolog 1 (HEG1), is a highly specific marker for MM. 28361969 2 4 theme mucin-like 321:330 arg1 protein 341:347 a novel mucin-like membrane protein 313:347 a novel mucin-like membrane protein 313:347 Here, we show that a novel mucin-like membrane protein, sialylated protein HEG homolog 1 (HEG1), is a highly specific marker for MM. 28361969 5 5 with glycan 754:759 arg1 peptide 771:777 HEG1 peptide 766:777 HEG1 peptide 766:777 This accurate discrimination by SKM9-2 was due to the recognition of a sialylated O-linked glycan with HEG1 peptide. 28361969 7 6 theme sialylated 1032:1041 arg1 HEG1 1043:1046 sialylated HEG1 1032:1046 sialylated HEG1 1032:1046 Taken together, our results indicate that sialylated HEG1 may be useful as a diagnostic and therapeutic target for MM. 28361969 2 7 theme novel 315:319 arg1 marker 412:417 a highly specific marker 394:417 a highly specific marker for MM 394:424 Here, we show that a novel mucin-like membrane protein, sialylated protein HEG homolog 1 (HEG1), is a highly specific marker for MM. 28361969 2 7 theme novel 315:319 arg1 homolog 373:379 sialylated protein HEG homolog 1 350:381 sialylated protein HEG homolog 1 (HEG1) 350:388 Here, we show that a novel mucin-like membrane protein, sialylated protein HEG homolog 1 (HEG1), is a highly specific marker for MM. 28361969 2 7 theme novel 315:319 arg1 protein 341:347 a novel mucin-like membrane protein 313:347 a novel mucin-like membrane protein 313:347 Here, we show that a novel mucin-like membrane protein, sialylated protein HEG homolog 1 (HEG1), is a highly specific marker for MM. 28361969 0 8 theme therapeutic 76:86 arg1 protein 36:42 a novel mucin-like membrane protein 8:42 a novel mucin-like membrane protein that serves as a diagnostic and therapeutic target for malignant mesothelioma 8:120 HEG1 is a novel mucin-like membrane protein that serves as a diagnostic and therapeutic target for malignant mesothelioma. 28361969 0 8 theme therapeutic 76:86 arg1 target 88:93 a diagnostic and therapeutic target 59:93 a diagnostic and therapeutic target for malignant mesothelioma 59:120 HEG1 is a novel mucin-like membrane protein that serves as a diagnostic and therapeutic target for malignant mesothelioma. 28361969 6 9 theme gene 799:802 arg1 silencing 804:812 gene silencing 799:812 gene silencing of HEG1 799:820 We also found that gene silencing of HEG1 significantly suppressed the survival and proliferation of mesothelioma cells; this result suggests that HEG1 may be a worthwhile target for function-inhibition drugs. 28361969 4 10 theme normal 647:652 arg1 tissues 654:660 normal tissues 647:660 normal tissues 647:660 The specificity and sensitivity of SKM9-2 to MM reached 99% and 92%, respectively; this antibody did not react with normal tissues. 28361969 3 11 gly sialylated 457:466 arg1 HEG1 468:471 sialylated HEG1 457:471 sialylated HEG1 457:471 A monoclonal antibody against sialylated HEG1, SKM9-2, can detect even sarcomatoid and desmoplastic MM. 28361969 6 12 theme cells 894:898 arg1 proliferation 864:876 proliferation 864:876 proliferation 864:876 We also found that gene silencing of HEG1 significantly suppressed the survival and proliferation of mesothelioma cells; this result suggests that HEG1 may be a worthwhile target for function-inhibition drugs. 28361969 6 12 theme cells 894:898 arg1 survival 851:858 survival 851:858 survival 851:858 We also found that gene silencing of HEG1 significantly suppressed the survival and proliferation of mesothelioma cells; this result suggests that HEG1 may be a worthwhile target for function-inhibition drugs. 28361969 7 13 theme therapeutic 1082:1092 arg1 target 1094:1099 a diagnostic and therapeutic target 1065:1099 a diagnostic and therapeutic target for MM 1065:1106 Taken together, our results indicate that sialylated HEG1 may be useful as a diagnostic and therapeutic target for MM. 28361969 5 14 gly sialylated 734:743 arg1 glycan 754:759 a sialylated O-linked glycan 732:759 a sialylated O-linked glycan with HEG1 peptide 732:777 This accurate discrimination by SKM9-2 was due to the recognition of a sialylated O-linked glycan with HEG1 peptide. 28361969 5 15 theme sialylated 734:743 arg1 glycan 754:759 a sialylated O-linked glycan 732:759 a sialylated O-linked glycan with HEG1 peptide 732:777 This accurate discrimination by SKM9-2 was due to the recognition of a sialylated O-linked glycan with HEG1 peptide. 28361969 2 16 theme sialylated 350:359 arg1 protein 341:347 a novel mucin-like membrane protein 313:347 a novel mucin-like membrane protein 313:347 Here, we show that a novel mucin-like membrane protein, sialylated protein HEG homolog 1 (HEG1), is a highly specific marker for MM. 28361969 2 16 theme sialylated 350:359 arg1 homolog 373:379 sialylated protein HEG homolog 1 350:381 sialylated protein HEG homolog 1 (HEG1) 350:388 Here, we show that a novel mucin-like membrane protein, sialylated protein HEG homolog 1 (HEG1), is a highly specific marker for MM. 28361969 2 16 theme sialylated 350:359 arg1 HEG1 384:387 HEG1 384:387 HEG1 384:387 Here, we show that a novel mucin-like membrane protein, sialylated protein HEG homolog 1 (HEG1), is a highly specific marker for MM. 28361969 1 17 theme markers 154:160 arg1 absence 127:133 The absence 123:133 The absence of highly specific markers for malignant mesothelioma (MM) 123:192 The absence of highly specific markers for malignant mesothelioma (MM) has served an obstacle for its diagnosis and development of molecular-targeting therapy against MM. 28361969 2 18 theme protein 361:367 arg1 protein 341:347 a novel mucin-like membrane protein 313:347 a novel mucin-like membrane protein 313:347 Here, we show that a novel mucin-like membrane protein, sialylated protein HEG homolog 1 (HEG1), is a highly specific marker for MM. 28361969 2 18 theme protein 361:367 arg1 homolog 373:379 sialylated protein HEG homolog 1 350:381 sialylated protein HEG homolog 1 (HEG1) 350:388 Here, we show that a novel mucin-like membrane protein, sialylated protein HEG homolog 1 (HEG1), is a highly specific marker for MM. 28361969 2 18 theme protein 361:367 arg1 HEG1 384:387 HEG1 384:387 HEG1 384:387 Here, we show that a novel mucin-like membrane protein, sialylated protein HEG homolog 1 (HEG1), is a highly specific marker for MM. 28361969 3 19 dep sarcomatoid 498:508 arg1 MM 527:528 MM 527:528 MM 527:528 A monoclonal antibody against sialylated HEG1, SKM9-2, can detect even sarcomatoid and desmoplastic MM. 28361969 6 20 theme function-inhibition 963:981 arg1 drugs 983:987 function-inhibition drugs 963:987 function-inhibition drugs 963:987 We also found that gene silencing of HEG1 significantly suppressed the survival and proliferation of mesothelioma cells; this result suggests that HEG1 may be a worthwhile target for function-inhibition drugs. 28361969 1 21 theme malignant 166:174 arg1 MM 190:191 MM 190:191 MM 190:191 The absence of highly specific markers for malignant mesothelioma (MM) has served an obstacle for its diagnosis and development of molecular-targeting therapy against MM. 28361969 1 21 theme malignant 166:174 arg1 mesothelioma 176:187 malignant mesothelioma 166:187 malignant mesothelioma (MM) 166:192 The absence of highly specific markers for malignant mesothelioma (MM) has served an obstacle for its diagnosis and development of molecular-targeting therapy against MM. 28361969 6 22 theme mesothelioma 881:892 arg1 cells 894:898 mesothelioma cells 881:898 mesothelioma cells 881:898 We also found that gene silencing of HEG1 significantly suppressed the survival and proliferation of mesothelioma cells; this result suggests that HEG1 may be a worthwhile target for function-inhibition drugs. 28361969 2 23 gly sialylated 350:359 arg1 protein 341:347 a novel mucin-like membrane protein 313:347 a novel mucin-like membrane protein 313:347 Here, we show that a novel mucin-like membrane protein, sialylated protein HEG homolog 1 (HEG1), is a highly specific marker for MM. 28361969 2 23 gly sialylated 350:359 arg1 homolog 373:379 sialylated protein HEG homolog 1 350:381 sialylated protein HEG homolog 1 (HEG1) 350:388 Here, we show that a novel mucin-like membrane protein, sialylated protein HEG homolog 1 (HEG1), is a highly specific marker for MM. 28361969 2 23 gly sialylated 350:359 arg1 HEG1 384:387 HEG1 384:387 HEG1 384:387 Here, we show that a novel mucin-like membrane protein, sialylated protein HEG homolog 1 (HEG1), is a highly specific marker for MM. 28361969 0 24 theme novel 10:14 arg1 target 88:93 a diagnostic and therapeutic target 59:93 a diagnostic and therapeutic target for malignant mesothelioma 59:120 HEG1 is a novel mucin-like membrane protein that serves as a diagnostic and therapeutic target for malignant mesothelioma. 28361969 0 24 theme novel 10:14 arg1 HEG1 0:3 HEG1 0:3 HEG1 0:3 HEG1 is a novel mucin-like membrane protein that serves as a diagnostic and therapeutic target for malignant mesothelioma. 28361969 0 24 theme novel 10:14 arg1 protein 36:42 a novel mucin-like membrane protein 8:42 a novel mucin-like membrane protein that serves as a diagnostic and therapeutic target for malignant mesothelioma 8:120 HEG1 is a novel mucin-like membrane protein that serves as a diagnostic and therapeutic target for malignant mesothelioma. 28361969 1 25 theme molecular-targeting 254:272 arg1 therapy 274:280 molecular-targeting therapy 254:280 molecular-targeting therapy against MM 254:291 The absence of highly specific markers for malignant mesothelioma (MM) has served an obstacle for its diagnosis and development of molecular-targeting therapy against MM. 28361969 7 26 gly sialylated 1032:1041 arg1 HEG1 1043:1046 sialylated HEG1 1032:1046 sialylated HEG1 1032:1046 Taken together, our results indicate that sialylated HEG1 may be useful as a diagnostic and therapeutic target for MM. 28361969 1 27 theme therapy 274:280 arg1 diagnosis 225:233 diagnosis 225:233 diagnosis 225:233 The absence of highly specific markers for malignant mesothelioma (MM) has served an obstacle for its diagnosis and development of molecular-targeting therapy against MM. 28361969 1 27 theme therapy 274:280 arg1 development 239:249 development 239:249 development 239:249 The absence of highly specific markers for malignant mesothelioma (MM) has served an obstacle for its diagnosis and development of molecular-targeting therapy against MM. 28361969 0 28 theme malignant 99:107 arg1 mesothelioma 109:120 malignant mesothelioma 99:120 malignant mesothelioma 99:120 HEG1 is a novel mucin-like membrane protein that serves as a diagnostic and therapeutic target for malignant mesothelioma. 28361969 1 29 theme specific 145:152 arg1 markers 154:160 highly specific markers 138:160 highly specific markers for malignant mesothelioma (MM) 138:192 The absence of highly specific markers for malignant mesothelioma (MM) has served an obstacle for its diagnosis and development of molecular-targeting therapy against MM. 28361969 4 30 theme SKM9-2 566:571 arg1 sensitivity 551:561 sensitivity 551:561 sensitivity 551:561 The specificity and sensitivity of SKM9-2 to MM reached 99% and 92%, respectively; this antibody did not react with normal tissues. 28361969 4 30 theme SKM9-2 566:571 arg1 specificity 535:545 specificity 535:545 specificity 535:545 The specificity and sensitivity of SKM9-2 to MM reached 99% and 92%, respectively; this antibody did not react with normal tissues. 28361969 0 31 theme membrane 27:34 arg1 target 88:93 a diagnostic and therapeutic target 59:93 a diagnostic and therapeutic target for malignant mesothelioma 59:120 HEG1 is a novel mucin-like membrane protein that serves as a diagnostic and therapeutic target for malignant mesothelioma. 28361969 0 31 theme membrane 27:34 arg1 HEG1 0:3 HEG1 0:3 HEG1 0:3 HEG1 is a novel mucin-like membrane protein that serves as a diagnostic and therapeutic target for malignant mesothelioma. 28361969 0 31 theme membrane 27:34 arg1 protein 36:42 a novel mucin-like membrane protein 8:42 a novel mucin-like membrane protein that serves as a diagnostic and therapeutic target for malignant mesothelioma 8:120 HEG1 is a novel mucin-like membrane protein that serves as a diagnostic and therapeutic target for malignant mesothelioma. 28361969 5 32 theme O-linked 745:752 arg1 glycan 754:759 a sialylated O-linked glycan 732:759 a sialylated O-linked glycan with HEG1 peptide 732:777 This accurate discrimination by SKM9-2 was due to the recognition of a sialylated O-linked glycan with HEG1 peptide. 28361969 2 33 theme HEG 369:371 arg1 protein 341:347 a novel mucin-like membrane protein 313:347 a novel mucin-like membrane protein 313:347 Here, we show that a novel mucin-like membrane protein, sialylated protein HEG homolog 1 (HEG1), is a highly specific marker for MM. 28361969 2 33 theme HEG 369:371 arg1 homolog 373:379 sialylated protein HEG homolog 1 350:381 sialylated protein HEG homolog 1 (HEG1) 350:388 Here, we show that a novel mucin-like membrane protein, sialylated protein HEG homolog 1 (HEG1), is a highly specific marker for MM. 28361969 2 33 theme HEG 369:371 arg1 HEG1 384:387 HEG1 384:387 HEG1 384:387 Here, we show that a novel mucin-like membrane protein, sialylated protein HEG homolog 1 (HEG1), is a highly specific marker for MM. 28361969 0 34 theme mucin-like 16:25 arg1 target 88:93 a diagnostic and therapeutic target 59:93 a diagnostic and therapeutic target for malignant mesothelioma 59:120 HEG1 is a novel mucin-like membrane protein that serves as a diagnostic and therapeutic target for malignant mesothelioma. 28361969 0 34 theme mucin-like 16:25 arg1 HEG1 0:3 HEG1 0:3 HEG1 0:3 HEG1 is a novel mucin-like membrane protein that serves as a diagnostic and therapeutic target for malignant mesothelioma. 28361969 0 34 theme mucin-like 16:25 arg1 protein 36:42 a novel mucin-like membrane protein 8:42 a novel mucin-like membrane protein that serves as a diagnostic and therapeutic target for malignant mesothelioma 8:120 HEG1 is a novel mucin-like membrane protein that serves as a diagnostic and therapeutic target for malignant mesothelioma. 28361969 6 35 dep survival 851:858 arg1 the 847:849 the 847:849 the 847:849 We also found that gene silencing of HEG1 significantly suppressed the survival and proliferation of mesothelioma cells; this result suggests that HEG1 may be a worthwhile target for function-inhibition drugs. 28361969 5 36 theme glycan 754:759 arg1 recognition 717:727 the recognition 713:727 the recognition of a sialylated O-linked glycan with HEG1 peptide 713:777 This accurate discrimination by SKM9-2 was due to the recognition of a sialylated O-linked glycan with HEG1 peptide. 28361969 2 37 theme specific 403:410 arg1 marker 412:417 a highly specific marker 394:417 a highly specific marker for MM 394:424 Here, we show that a novel mucin-like membrane protein, sialylated protein HEG homolog 1 (HEG1), is a highly specific marker for MM. 28361969 2 37 theme specific 403:410 arg1 protein 341:347 a novel mucin-like membrane protein 313:347 a novel mucin-like membrane protein 313:347 Here, we show that a novel mucin-like membrane protein, sialylated protein HEG homolog 1 (HEG1), is a highly specific marker for MM. 28361969 3 38 theme monoclonal 429:438 arg1 SKM9-2 474:479 SKM9-2 474:479 SKM9-2 474:479 A monoclonal antibody against sialylated HEG1, SKM9-2, can detect even sarcomatoid and desmoplastic MM. 28361969 3 38 theme monoclonal 429:438 arg1 antibody 440:447 A monoclonal antibody 427:447 A monoclonal antibody against sialylated HEG1 427:471 A monoclonal antibody against sialylated HEG1, SKM9-2, can detect even sarcomatoid and desmoplastic MM. 28361969 7 39 theme diagnostic 1067:1076 arg1 target 1094:1099 a diagnostic and therapeutic target 1065:1099 a diagnostic and therapeutic target for MM 1065:1106 Taken together, our results indicate that sialylated HEG1 may be useful as a diagnostic and therapeutic target for MM. 28361969 4 40 dep specificity 535:545 arg1 The 531:533 The 531:533 The 531:533 The specificity and sensitivity of SKM9-2 to MM reached 99% and 92%, respectively; this antibody did not react with normal tissues. 28361969 3 41 theme sialylated 457:466 arg1 HEG1 468:471 sialylated HEG1 457:471 sialylated HEG1 457:471 A monoclonal antibody against sialylated HEG1, SKM9-2, can detect even sarcomatoid and desmoplastic MM. 28361969 5 42 theme HEG1 766:769 arg1 peptide 771:777 HEG1 peptide 766:777 HEG1 peptide 766:777 This accurate discrimination by SKM9-2 was due to the recognition of a sialylated O-linked glycan with HEG1 peptide. 28361969 6 43 theme HEG1 817:820 arg1 silencing 804:812 gene silencing 799:812 gene silencing of HEG1 799:820 We also found that gene silencing of HEG1 significantly suppressed the survival and proliferation of mesothelioma cells; this result suggests that HEG1 may be a worthwhile target for function-inhibition drugs. 28361969 2 44 theme membrane 332:339 arg1 marker 412:417 a highly specific marker 394:417 a highly specific marker for MM 394:424 Here, we show that a novel mucin-like membrane protein, sialylated protein HEG homolog 1 (HEG1), is a highly specific marker for MM. 28361969 2 44 theme membrane 332:339 arg1 homolog 373:379 sialylated protein HEG homolog 1 350:381 sialylated protein HEG homolog 1 (HEG1) 350:388 Here, we show that a novel mucin-like membrane protein, sialylated protein HEG homolog 1 (HEG1), is a highly specific marker for MM. 28361969 2 44 theme membrane 332:339 arg1 protein 341:347 a novel mucin-like membrane protein 313:347 a novel mucin-like membrane protein 313:347 Here, we show that a novel mucin-like membrane protein, sialylated protein HEG homolog 1 (HEG1), is a highly specific marker for MM. 27558425 2 0 located located 624:630 arg2 each 606:609 each 606:609 each 606:609 We also detected the expression of four short ORFs, each of which was located within an ORF ("ORF-within-ORF"), including one not previously recognized or known to be expressed. 27558425 2 0 located located 624:630 arg2 ORFs 600:603 four short ORFs 589:603 four short ORFs 589:603 We also detected the expression of four short ORFs, each of which was located within an ORF ("ORF-within-ORF"), including one not previously recognized or known to be expressed. 27558425 2 0 located located 624:630 arg1 " 662:662 "ORF-within-ORF" 647:662 "ORF-within-ORF" 647:662 We also detected the expression of four short ORFs, each of which was located within an ORF ("ORF-within-ORF"), including one not previously recognized or known to be expressed. 27558425 2 0 located located 624:630 arg1 ORF 642:644 an ORF 639:644 an ORF ("ORF-within-ORF") 639:663 We also detected the expression of four short ORFs, each of which was located within an ORF ("ORF-within-ORF"), including one not previously recognized or known to be expressed. 27558425 14 1 theme structure 2329:2337 arg1 study 2307:2311 a deep study 2300:2311 a deep study of the covalent structure of the vaccinia virus virion using the various tools of contemporary mass spectrometry 2300:2424 Here, we provide a deep study of the covalent structure of the vaccinia virus virion using the various tools of contemporary mass spectrometry. 27558425 0 2 theme virion 142:147 arg1 structure 110:118 the protein covalent structure 89:118 the protein covalent structure of the vaccinia virus virion 89:147 Protein Primary Structure of the Vaccinia Virion at Increased Resolution Here we examine the protein covalent structure of the vaccinia virus virion. 27558425 6 3 dep http 1288:1291 arg1 //dx.doi.org/10.1016/j.virol.2014.01.012 1293:1332 //dx.doi.org/10.1016/j.virol.2014.01.012 1293:1332 http://dx.doi.org/10.1016/j.virol.2014.01.012 1288:1332 The size of the characterized virion phosphoproteome was doubled from 189 (J. Matson, W. Chou, T. Ngo, and P. D. Gershon, Virology 452-453:310-323, 2014, doi:http://dx.doi.org/10.1016/j.virol.2014.01.012) to 396 confident, unique phosphorylation sites, 268 of which were within the packaged proteome. 27558425 10 4 theme protein 1890:1896 arg1 modifications 1898:1910 protein modifications 1890:1910 protein modifications 1890:1910 In a blind search for protein modifications, cysteine glutathionylation and O-linked glycosylation featured prominently. 27558425 1 5 from detection 293:301 arg1 ORFs 344:347 ORFs 344:347 ORFs 344:347 Within two virion preparations, >88% of the theoretical vaccinia virus-encoded proteome was detected with high confidence, including the first detection of products from 27 open reading frames (ORFs) previously designated "predicted," "uncharacterized," "inferred," or "hypothetical" polypeptides containing as few as 39 amino acids (aa) and six proteins whose detection required nontryptic proteolysis. 27558425 1 5 from detection 293:301 arg1 frames 336:341 27 open reading frames 320:341 27 open reading frames (ORFs) previously designated "predicted," "uncharacterized," "inferred," or "hypothetical" polypeptides containing as few as 39 amino acids (aa) and six proteins whose detection required nontryptic proteolysis 320:551 Within two virion preparations, >88% of the theoretical vaccinia virus-encoded proteome was detected with high confidence, including the first detection of products from 27 open reading frames (ORFs) previously designated "predicted," "uncharacterized," "inferred," or "hypothetical" polypeptides containing as few as 39 amino acids (aa) and six proteins whose detection required nontryptic proteolysis. 27558425 1 6 theme high 256:259 arg1 confidence 261:270 high confidence 256:270 high confidence 256:270 Within two virion preparations, >88% of the theoretical vaccinia virus-encoded proteome was detected with high confidence, including the first detection of products from 27 open reading frames (ORFs) previously designated "predicted," "uncharacterized," "inferred," or "hypothetical" polypeptides containing as few as 39 amino acids (aa) and six proteins whose detection required nontryptic proteolysis. 27558425 2 7 theme ORF-within-ORF 648:661 arg1 " 662:662 "ORF-within-ORF" 647:662 "ORF-within-ORF" 647:662 We also detected the expression of four short ORFs, each of which was located within an ORF ("ORF-within-ORF"), including one not previously recognized or known to be expressed. 27558425 2 7 theme ORF-within-ORF 648:661 arg1 ORF 642:644 an ORF 639:644 an ORF ("ORF-within-ORF") 639:663 We also detected the expression of four short ORFs, each of which was located within an ORF ("ORF-within-ORF"), including one not previously recognized or known to be expressed. 27558425 1 8 theme virion 161:166 arg1 preparations 168:179 two virion preparations 157:179 two virion preparations 157:179 Within two virion preparations, >88% of the theoretical vaccinia virus-encoded proteome was detected with high confidence, including the first detection of products from 27 open reading frames (ORFs) previously designated "predicted," "uncharacterized," "inferred," or "hypothetical" polypeptides containing as few as 39 amino acids (aa) and six proteins whose detection required nontryptic proteolysis. 27558425 8 9 theme virion 1705:1710 arg1 preparations 1712:1723 the virion preparations 1701:1723 the virion preparations 1701:1723 Using isotopically enriched ATP, 23 sites of intravirion kinase phosphorylation were detected within nine virion proteins, all at sites already partially occupied within the virion preparations. 27558425 6 10 dep confident 1342:1350 arg1 unique 1353:1358 unique 1353:1358 unique 1353:1358 The size of the characterized virion phosphoproteome was doubled from 189 (J. Matson, W. Chou, T. Ngo, and P. D. Gershon, Virology 452-453:310-323, 2014, doi:http://dx.doi.org/10.1016/j.virol.2014.01.012) to 396 confident, unique phosphorylation sites, 268 of which were within the packaged proteome. 27558425 9 11 theme proteins 1755:1762 arg1 consistent 1783:1792 consistent 1783:1792 consistent 1783:1792 The clear phosphorylation of proteins RAP94 and RP19 was consistent with the roles of these proteins in intravirion early gene transcription. 27558425 9 11 theme proteins 1755:1762 arg1 phosphorylation 1736:1750 The clear phosphorylation 1726:1750 The clear phosphorylation of proteins RAP94 and RP19 1726:1777 The clear phosphorylation of proteins RAP94 and RP19 was consistent with the roles of these proteins in intravirion early gene transcription. 27558425 6 12 theme virion 1160:1165 arg1 phosphoproteome 1167:1181 the characterized virion phosphoproteome 1142:1181 the characterized virion phosphoproteome 1142:1181 The size of the characterized virion phosphoproteome was doubled from 189 (J. Matson, W. Chou, T. Ngo, and P. D. Gershon, Virology 452-453:310-323, 2014, doi:http://dx.doi.org/10.1016/j.virol.2014.01.012) to 396 confident, unique phosphorylation sites, 268 of which were within the packaged proteome. 27558425 0 13 theme virus 136:140 arg1 virion 142:147 the vaccinia virus virion 123:147 the vaccinia virus virion 123:147 Protein Primary Structure of the Vaccinia Virion at Increased Resolution Here we examine the protein covalent structure of the vaccinia virus virion. 27558425 3 14 theme quantitative 738:749 arg1 MS 770:771 MS 770:771 MS 770:771 Using quantitative mass spectrometry (MS), between 58 and 74 proteins were determined to be packaged. 27558425 3 14 theme quantitative 738:749 arg1 spectrometry 756:767 quantitative mass spectrometry 738:767 quantitative mass spectrometry (MS) 738:772 Using quantitative mass spectrometry (MS), between 58 and 74 proteins were determined to be packaged. 27558425 5 15 theme procedures 1118:1127 arg1 independent 1076:1086 independent 1076:1086 independent 1076:1086 Evidence is provided that some portion of virion proteins are "nicked" via a combination of endoproteolysis and concerted exoproteolysis in a manner, and at sites, independent of virus origin or laboratory procedures. 27558425 5 16 from sites 1069:1073 arg1 manner 1054:1059 a manner 1052:1059 a manner 1052:1059 Evidence is provided that some portion of virion proteins are "nicked" via a combination of endoproteolysis and concerted exoproteolysis in a manner, and at sites, independent of virus origin or laboratory procedures. 27558425 8 17 theme kinase 1588:1593 arg1 phosphorylation 1595:1609 intravirion kinase phosphorylation 1576:1609 intravirion kinase phosphorylation 1576:1609 Using isotopically enriched ATP, 23 sites of intravirion kinase phosphorylation were detected within nine virion proteins, all at sites already partially occupied within the virion preparations. 27558425 1 18 contain containing 447:456 arg2 proteins 496:503 six proteins 492:503 six proteins whose detection required nontryptic proteolysis 492:551 Within two virion preparations, >88% of the theoretical vaccinia virus-encoded proteome was detected with high confidence, including the first detection of products from 27 open reading frames (ORFs) previously designated "predicted," "uncharacterized," "inferred," or "hypothetical" polypeptides containing as few as 39 amino acids (aa) and six proteins whose detection required nontryptic proteolysis. 27558425 1 18 contain containing 447:456 arg1 " 383:383 " 383:383 " "uncharacterized 383:400 Within two virion preparations, >88% of the theoretical vaccinia virus-encoded proteome was detected with high confidence, including the first detection of products from 27 open reading frames (ORFs) previously designated "predicted," "uncharacterized," "inferred," or "hypothetical" polypeptides containing as few as 39 amino acids (aa) and six proteins whose detection required nontryptic proteolysis. 27558425 1 18 contain containing 447:456 arg2 aa 484:485 aa 484:485 aa 484:485 Within two virion preparations, >88% of the theoretical vaccinia virus-encoded proteome was detected with high confidence, including the first detection of products from 27 open reading frames (ORFs) previously designated "predicted," "uncharacterized," "inferred," or "hypothetical" polypeptides containing as few as 39 amino acids (aa) and six proteins whose detection required nontryptic proteolysis. 27558425 1 18 contain containing 447:456 arg2 acids 477:481 as few as 39 amino acids 458:481 as few as 39 amino acids (aa) 458:486 Within two virion preparations, >88% of the theoretical vaccinia virus-encoded proteome was detected with high confidence, including the first detection of products from 27 open reading frames (ORFs) previously designated "predicted," "uncharacterized," "inferred," or "hypothetical" polypeptides containing as few as 39 amino acids (aa) and six proteins whose detection required nontryptic proteolysis. 27558425 1 19 theme nontryptic 530:539 arg1 proteolysis 541:551 nontryptic proteolysis 530:551 nontryptic proteolysis 530:551 Within two virion preparations, >88% of the theoretical vaccinia virus-encoded proteome was detected with high confidence, including the first detection of products from 27 open reading frames (ORFs) previously designated "predicted," "uncharacterized," "inferred," or "hypothetical" polypeptides containing as few as 39 amino acids (aa) and six proteins whose detection required nontryptic proteolysis. 27558425 0 20 theme Increased 52:60 arg1 Resolution 62:71 Increased Resolution 52:71 Increased Resolution 52:71 Protein Primary Structure of the Vaccinia Virion at Increased Resolution Here we examine the protein covalent structure of the vaccinia virus virion. 27558425 6 21 theme phosphorylation 1360:1374 arg1 sites 1376:1380 396 confident, unique phosphorylation sites 1338:1380 396 confident, unique phosphorylation sites 1338:1380 The size of the characterized virion phosphoproteome was doubled from 189 (J. Matson, W. Chou, T. Ngo, and P. D. Gershon, Virology 452-453:310-323, 2014, doi:http://dx.doi.org/10.1016/j.virol.2014.01.012) to 396 confident, unique phosphorylation sites, 268 of which were within the packaged proteome. 27558425 11 22 theme proteins 2056:2063 arg1 phosphoglycosylation 2017:2036 the phosphoglycosylation 2013:2036 the phosphoglycosylation of vaccinia virus proteins 2013:2063 We provide evidence for the phosphoglycosylation of vaccinia virus proteins. 27558425 5 23 theme virus 1091:1095 arg1 origin 1097:1102 virus origin 1091:1102 virus origin 1091:1102 Evidence is provided that some portion of virion proteins are "nicked" via a combination of endoproteolysis and concerted exoproteolysis in a manner, and at sites, independent of virus origin or laboratory procedures. 27558425 9 24 with consistent 1783:1792 arg1 roles 1803:1807 the roles 1799:1807 the roles of these proteins in intravirion early gene transcription 1799:1865 The clear phosphorylation of proteins RAP94 and RP19 was consistent with the roles of these proteins in intravirion early gene transcription. 27558425 1 25 theme open 323:326 arg1 ORFs 344:347 ORFs 344:347 ORFs 344:347 Within two virion preparations, >88% of the theoretical vaccinia virus-encoded proteome was detected with high confidence, including the first detection of products from 27 open reading frames (ORFs) previously designated "predicted," "uncharacterized," "inferred," or "hypothetical" polypeptides containing as few as 39 amino acids (aa) and six proteins whose detection required nontryptic proteolysis. 27558425 1 25 theme open 323:326 arg1 frames 336:341 27 open reading frames 320:341 27 open reading frames (ORFs) previously designated "predicted," "uncharacterized," "inferred," or "hypothetical" polypeptides containing as few as 39 amino acids (aa) and six proteins whose detection required nontryptic proteolysis 320:551 Within two virion preparations, >88% of the theoretical vaccinia virus-encoded proteome was detected with high confidence, including the first detection of products from 27 open reading frames (ORFs) previously designated "predicted," "uncharacterized," "inferred," or "hypothetical" polypeptides containing as few as 39 amino acids (aa) and six proteins whose detection required nontryptic proteolysis. 27558425 14 26 theme mass 2408:2411 arg1 spectrometry 2413:2424 contemporary mass spectrometry 2395:2424 contemporary mass spectrometry 2395:2424 Here, we provide a deep study of the covalent structure of the vaccinia virus virion using the various tools of contemporary mass spectrometry. 27558425 8 27 theme virion 1637:1642 arg1 all 1654:1656 all 1654:1656 all 1654:1656 Using isotopically enriched ATP, 23 sites of intravirion kinase phosphorylation were detected within nine virion proteins, all at sites already partially occupied within the virion preparations. 27558425 8 27 theme virion 1637:1642 arg1 proteins 1644:1651 nine virion proteins 1632:1651 nine virion proteins 1632:1651 Using isotopically enriched ATP, 23 sites of intravirion kinase phosphorylation were detected within nine virion proteins, all at sites already partially occupied within the virion preparations. 27558425 7 28 theme spots 1500:1504 arg1 identification 1461:1474 the unambiguous identification 1445:1474 the unambiguous identification of phosphorylation "hot spots" within virion proteins 1445:1528 This included the unambiguous identification of phosphorylation "hot spots" within virion proteins. 27558425 12 29 theme complex 2107:2113 arg1 virions 2129:2135 the most complex and irregular virions 2098:2135 the most complex and irregular virions 2098:2135 IMPORTANCE Poxviruses are among the most complex and irregular virions, about whose internal structure little is known. 27558425 9 30 theme early 1842:1846 arg1 transcription 1853:1865 intravirion early gene transcription 1830:1865 intravirion early gene transcription 1830:1865 The clear phosphorylation of proteins RAP94 and RP19 was consistent with the roles of these proteins in intravirion early gene transcription. 27558425 12 31 theme most 2102:2105 arg1 virions 2129:2135 the most complex and irregular virions 2098:2135 the most complex and irregular virions 2098:2135 IMPORTANCE Poxviruses are among the most complex and irregular virions, about whose internal structure little is known. 27558425 0 32 theme protein 93:99 arg1 structure 110:118 the protein covalent structure 89:118 the protein covalent structure of the vaccinia virus virion 89:147 Protein Primary Structure of the Vaccinia Virion at Increased Resolution Here we examine the protein covalent structure of the vaccinia virus virion. 27558425 5 33 theme proteins 961:968 arg1 " 981:981 "nicked" 974:981 "nicked" 974:981 Evidence is provided that some portion of virion proteins are "nicked" via a combination of endoproteolysis and concerted exoproteolysis in a manner, and at sites, independent of virus origin or laboratory procedures. 27558425 5 33 theme proteins 961:968 arg1 portion 943:949 some portion 938:949 some portion of virion proteins 938:968 Evidence is provided that some portion of virion proteins are "nicked" via a combination of endoproteolysis and concerted exoproteolysis in a manner, and at sites, independent of virus origin or laboratory procedures. 27558425 0 34 theme Vaccinia 33:40 arg1 Virion 42:47 the Vaccinia Virion 29:47 the Vaccinia Virion 29:47 Protein Primary Structure of the Vaccinia Virion at Increased Resolution Here we examine the protein covalent structure of the vaccinia virus virion. 27558425 12 35 theme irregular 2119:2127 arg1 virions 2129:2135 the most complex and irregular virions 2098:2135 the most complex and irregular virions 2098:2135 IMPORTANCE Poxviruses are among the most complex and irregular virions, about whose internal structure little is known. 27558425 2 36 theme ORFs 600:603 arg1 expression 575:584 the expression 571:584 the expression of four short ORFs, each of which was located within an ORF ("ORF-within-ORF"), including one not previously recognized or known to be expressed 571:729 We also detected the expression of four short ORFs, each of which was located within an ORF ("ORF-within-ORF"), including one not previously recognized or known to be expressed. 27558425 0 37 theme Protein 0:6 arg1 Structure 16:24 Protein Primary Structure 0:24 Protein Primary Structure of the Vaccinia Virion at Increased Resolution 0:71 Protein Primary Structure of the Vaccinia Virion at Increased Resolution Here we examine the protein covalent structure of the vaccinia virus virion. 27558425 13 38 theme other 2270:2274 arg1 tools 2276:2280 other tools 2270:2280 other tools 2270:2280 To better understand poxvirus virion structure, imaging should be supplemented with other tools. 27558425 9 39 from roles 1803:1807 arg1 transcription 1853:1865 intravirion early gene transcription 1830:1865 intravirion early gene transcription 1830:1865 The clear phosphorylation of proteins RAP94 and RP19 was consistent with the roles of these proteins in intravirion early gene transcription. 27558425 6 40 theme sites 1376:1380 arg1 sites 1376:1380 396 confident, unique phosphorylation sites 1338:1380 396 confident, unique phosphorylation sites 1338:1380 The size of the characterized virion phosphoproteome was doubled from 189 (J. Matson, W. Chou, T. Ngo, and P. D. Gershon, Virology 452-453:310-323, 2014, doi:http://dx.doi.org/10.1016/j.virol.2014.01.012) to 396 confident, unique phosphorylation sites, 268 of which were within the packaged proteome. 27558425 6 40 theme sites 1376:1380 arg1 268 1383:1385 268 1383:1385 268 1383:1385 The size of the characterized virion phosphoproteome was doubled from 189 (J. Matson, W. Chou, T. Ngo, and P. D. Gershon, Virology 452-453:310-323, 2014, doi:http://dx.doi.org/10.1016/j.virol.2014.01.012) to 396 confident, unique phosphorylation sites, 268 of which were within the packaged proteome. 27558425 5 41 theme exoproteolysis 1034:1047 arg1 combination 989:999 a combination 987:999 a combination of endoproteolysis and concerted exoproteolysis 987:1047 Evidence is provided that some portion of virion proteins are "nicked" via a combination of endoproteolysis and concerted exoproteolysis in a manner, and at sites, independent of virus origin or laboratory procedures. 27558425 7 42 theme unambiguous 1449:1459 arg1 identification 1461:1474 the unambiguous identification 1445:1474 the unambiguous identification of phosphorylation "hot spots" within virion proteins 1445:1528 This included the unambiguous identification of phosphorylation "hot spots" within virion proteins. 27558425 4 43 theme proteins 853:860 arg1 total 836:840 A total 834:840 A total of 63 host proteins 834:860 A total of 63 host proteins were also identified as candidates for packaging. 27558425 4 43 theme proteins 853:860 arg1 candidates 886:895 candidates 886:895 candidates for packaging 886:909 A total of 63 host proteins were also identified as candidates for packaging. 27558425 10 44 theme O-linked 1944:1951 arg1 glycosylation 1953:1965 O-linked glycosylation 1944:1965 O-linked glycosylation 1944:1965 In a blind search for protein modifications, cysteine glutathionylation and O-linked glycosylation featured prominently. 27558425 1 45 theme first 287:291 arg1 detection 293:301 the first detection 283:301 the first detection of products from 27 open reading frames (ORFs) previously designated "predicted," "uncharacterized," "inferred," or "hypothetical" polypeptides containing as few as 39 amino acids (aa) and six proteins whose detection required nontryptic proteolysis 283:551 Within two virion preparations, >88% of the theoretical vaccinia virus-encoded proteome was detected with high confidence, including the first detection of products from 27 open reading frames (ORFs) previously designated "predicted," "uncharacterized," "inferred," or "hypothetical" polypeptides containing as few as 39 amino acids (aa) and six proteins whose detection required nontryptic proteolysis. 27558425 11 46 theme virus 2050:2054 arg1 proteins 2056:2063 vaccinia virus proteins 2041:2063 vaccinia virus proteins 2041:2063 We provide evidence for the phosphoglycosylation of vaccinia virus proteins. 27558425 1 47 theme " 432:432 arg1 polypeptides 434:445 "hypothetical" polypeptides 419:445 "hypothetical" polypeptides 419:445 Within two virion preparations, >88% of the theoretical vaccinia virus-encoded proteome was detected with high confidence, including the first detection of products from 27 open reading frames (ORFs) previously designated "predicted," "uncharacterized," "inferred," or "hypothetical" polypeptides containing as few as 39 amino acids (aa) and six proteins whose detection required nontryptic proteolysis. 27558425 0 48 theme Virion 42:47 arg1 Structure 16:24 Protein Primary Structure 0:24 Protein Primary Structure of the Vaccinia Virion at Increased Resolution 0:71 Protein Primary Structure of the Vaccinia Virion at Increased Resolution Here we examine the protein covalent structure of the vaccinia virus virion. 27558425 14 49 theme virion 2361:2366 arg1 structure 2329:2337 the covalent structure 2316:2337 the covalent structure of the vaccinia virus virion 2316:2366 Here, we provide a deep study of the covalent structure of the vaccinia virus virion using the various tools of contemporary mass spectrometry. 27558425 1 50 theme theoretical 194:204 arg1 proteome 229:236 the theoretical vaccinia virus-encoded proteome 190:236 the theoretical vaccinia virus-encoded proteome 190:236 Within two virion preparations, >88% of the theoretical vaccinia virus-encoded proteome was detected with high confidence, including the first detection of products from 27 open reading frames (ORFs) previously designated "predicted," "uncharacterized," "inferred," or "hypothetical" polypeptides containing as few as 39 amino acids (aa) and six proteins whose detection required nontryptic proteolysis. 27558425 14 51 theme vaccinia 2346:2353 arg1 virion 2361:2366 the vaccinia virus virion 2342:2366 the vaccinia virus virion 2342:2366 Here, we provide a deep study of the covalent structure of the vaccinia virus virion using the various tools of contemporary mass spectrometry. 27558425 13 52 theme virion 2216:2221 arg1 structure 2223:2231 poxvirus virion structure 2207:2231 poxvirus virion structure 2207:2231 To better understand poxvirus virion structure, imaging should be supplemented with other tools. 27558425 10 53 theme blind 1873:1877 arg1 search 1879:1884 a blind search 1871:1884 a blind search for protein modifications 1871:1910 In a blind search for protein modifications, cysteine glutathionylation and O-linked glycosylation featured prominently. 27558425 1 54 theme virus-encoded 215:227 arg1 proteome 229:236 the theoretical vaccinia virus-encoded proteome 190:236 the theoretical vaccinia virus-encoded proteome 190:236 Within two virion preparations, >88% of the theoretical vaccinia virus-encoded proteome was detected with high confidence, including the first detection of products from 27 open reading frames (ORFs) previously designated "predicted," "uncharacterized," "inferred," or "hypothetical" polypeptides containing as few as 39 amino acids (aa) and six proteins whose detection required nontryptic proteolysis. 27558425 10 55 theme cysteine 1913:1920 arg1 glutathionylation 1922:1938 cysteine glutathionylation 1913:1938 cysteine glutathionylation 1913:1938 In a blind search for protein modifications, cysteine glutathionylation and O-linked glycosylation featured prominently. 27558425 14 56 theme covalent 2320:2327 arg1 structure 2329:2337 the covalent structure 2316:2337 the covalent structure of the vaccinia virus virion 2316:2366 Here, we provide a deep study of the covalent structure of the vaccinia virus virion using the various tools of contemporary mass spectrometry. 27558425 1 57 theme inferred 405:412 arg1 " 402:402 " 402:402 " "inferred 402:412 Within two virion preparations, >88% of the theoretical vaccinia virus-encoded proteome was detected with high confidence, including the first detection of products from 27 open reading frames (ORFs) previously designated "predicted," "uncharacterized," "inferred," or "hypothetical" polypeptides containing as few as 39 amino acids (aa) and six proteins whose detection required nontryptic proteolysis. 27558425 6 58 theme confident 1342:1350 arg1 sites 1376:1380 396 confident, unique phosphorylation sites 1338:1380 396 confident, unique phosphorylation sites 1338:1380 The size of the characterized virion phosphoproteome was doubled from 189 (J. Matson, W. Chou, T. Ngo, and P. D. Gershon, Virology 452-453:310-323, 2014, doi:http://dx.doi.org/10.1016/j.virol.2014.01.012) to 396 confident, unique phosphorylation sites, 268 of which were within the packaged proteome. 27558425 14 59 theme deep 2302:2305 arg1 study 2307:2311 a deep study 2300:2311 a deep study of the covalent structure of the vaccinia virus virion using the various tools of contemporary mass spectrometry 2300:2424 Here, we provide a deep study of the covalent structure of the vaccinia virus virion using the various tools of contemporary mass spectrometry. 27558425 9 60 theme clear 1730:1734 arg1 consistent 1783:1792 consistent 1783:1792 consistent 1783:1792 The clear phosphorylation of proteins RAP94 and RP19 was consistent with the roles of these proteins in intravirion early gene transcription. 27558425 9 60 theme clear 1730:1734 arg1 phosphorylation 1736:1750 The clear phosphorylation 1726:1750 The clear phosphorylation of proteins RAP94 and RP19 1726:1777 The clear phosphorylation of proteins RAP94 and RP19 was consistent with the roles of these proteins in intravirion early gene transcription. 27558425 6 61 theme phosphoproteome 1167:1181 arg1 size 1134:1137 The size 1130:1137 The size of the characterized virion phosphoproteome 1130:1181 The size of the characterized virion phosphoproteome was doubled from 189 (J. Matson, W. Chou, T. Ngo, and P. D. Gershon, Virology 452-453:310-323, 2014, doi:http://dx.doi.org/10.1016/j.virol.2014.01.012) to 396 confident, unique phosphorylation sites, 268 of which were within the packaged proteome. 27558425 8 62 theme enriched 1550:1557 arg1 ATP 1559:1561 isotopically enriched ATP 1537:1561 isotopically enriched ATP 1537:1561 Using isotopically enriched ATP, 23 sites of intravirion kinase phosphorylation were detected within nine virion proteins, all at sites already partially occupied within the virion preparations. 27558425 10 63 link O-linked 1944:1951 arg1 glycosylation 1953:1965 O-linked glycosylation 1944:1965 O-linked glycosylation 1944:1965 In a blind search for protein modifications, cysteine glutathionylation and O-linked glycosylation featured prominently. 27558425 0 64 from Resolution 62:71 arg1 Structure 16:24 Protein Primary Structure 0:24 Protein Primary Structure of the Vaccinia Virion at Increased Resolution 0:71 Protein Primary Structure of the Vaccinia Virion at Increased Resolution Here we examine the protein covalent structure of the vaccinia virus virion. 27558425 9 65 theme RP19 1774:1777 arg1 consistent 1783:1792 consistent 1783:1792 consistent 1783:1792 The clear phosphorylation of proteins RAP94 and RP19 was consistent with the roles of these proteins in intravirion early gene transcription. 27558425 9 65 theme RP19 1774:1777 arg1 phosphorylation 1736:1750 The clear phosphorylation 1726:1750 The clear phosphorylation of proteins RAP94 and RP19 1726:1777 The clear phosphorylation of proteins RAP94 and RP19 was consistent with the roles of these proteins in intravirion early gene transcription. 27558425 1 66 theme products 306:313 arg1 detection 293:301 the first detection 283:301 the first detection of products from 27 open reading frames (ORFs) previously designated "predicted," "uncharacterized," "inferred," or "hypothetical" polypeptides containing as few as 39 amino acids (aa) and six proteins whose detection required nontryptic proteolysis 283:551 Within two virion preparations, >88% of the theoretical vaccinia virus-encoded proteome was detected with high confidence, including the first detection of products from 27 open reading frames (ORFs) previously designated "predicted," "uncharacterized," "inferred," or "hypothetical" polypeptides containing as few as 39 amino acids (aa) and six proteins whose detection required nontryptic proteolysis. 27558425 6 67 theme characterized 1146:1158 arg1 phosphoproteome 1167:1181 the characterized virion phosphoproteome 1142:1181 the characterized virion phosphoproteome 1142:1181 The size of the characterized virion phosphoproteome was doubled from 189 (J. Matson, W. Chou, T. Ngo, and P. D. Gershon, Virology 452-453:310-323, 2014, doi:http://dx.doi.org/10.1016/j.virol.2014.01.012) to 396 confident, unique phosphorylation sites, 268 of which were within the packaged proteome. 27558425 1 68 theme predicted 373:381 arg1 " 383:383 " 383:383 " "uncharacterized 383:400 Within two virion preparations, >88% of the theoretical vaccinia virus-encoded proteome was detected with high confidence, including the first detection of products from 27 open reading frames (ORFs) previously designated "predicted," "uncharacterized," "inferred," or "hypothetical" polypeptides containing as few as 39 amino acids (aa) and six proteins whose detection required nontryptic proteolysis. 27558425 5 69 theme laboratory 1107:1116 arg1 procedures 1118:1127 laboratory procedures 1107:1127 laboratory procedures 1107:1127 Evidence is provided that some portion of virion proteins are "nicked" via a combination of endoproteolysis and concerted exoproteolysis in a manner, and at sites, independent of virus origin or laboratory procedures. 27558425 13 70 theme poxvirus 2207:2214 arg1 structure 2223:2231 poxvirus virion structure 2207:2231 poxvirus virion structure 2207:2231 To better understand poxvirus virion structure, imaging should be supplemented with other tools. 27558425 3 71 theme mass 751:754 arg1 MS 770:771 MS 770:771 MS 770:771 Using quantitative mass spectrometry (MS), between 58 and 74 proteins were determined to be packaged. 27558425 3 71 theme mass 751:754 arg1 spectrometry 756:767 quantitative mass spectrometry 738:767 quantitative mass spectrometry (MS) 738:772 Using quantitative mass spectrometry (MS), between 58 and 74 proteins were determined to be packaged. 27558425 8 72 located detected 1616:1623 arg2 phosphorylation 1595:1609 intravirion kinase phosphorylation 1576:1609 intravirion kinase phosphorylation 1576:1609 Using isotopically enriched ATP, 23 sites of intravirion kinase phosphorylation were detected within nine virion proteins, all at sites already partially occupied within the virion preparations. 27558425 8 72 located detected 1616:1623 arg1 all 1654:1656 all 1654:1656 all 1654:1656 Using isotopically enriched ATP, 23 sites of intravirion kinase phosphorylation were detected within nine virion proteins, all at sites already partially occupied within the virion preparations. 27558425 8 72 located detected 1616:1623 arg1 proteins 1644:1651 nine virion proteins 1632:1651 nine virion proteins 1632:1651 Using isotopically enriched ATP, 23 sites of intravirion kinase phosphorylation were detected within nine virion proteins, all at sites already partially occupied within the virion preparations. 27558425 8 72 located detected 1616:1623 arg2 sites 1567:1571 23 sites 1564:1571 23 sites of intravirion kinase phosphorylation 1564:1609 Using isotopically enriched ATP, 23 sites of intravirion kinase phosphorylation were detected within nine virion proteins, all at sites already partially occupied within the virion preparations. 27558425 1 73 theme uncharacterized 386:400 arg1 " 383:383 " 383:383 " "uncharacterized 383:400 Within two virion preparations, >88% of the theoretical vaccinia virus-encoded proteome was detected with high confidence, including the first detection of products from 27 open reading frames (ORFs) previously designated "predicted," "uncharacterized," "inferred," or "hypothetical" polypeptides containing as few as 39 amino acids (aa) and six proteins whose detection required nontryptic proteolysis. 27558425 8 74 theme intravirion 1576:1586 arg1 phosphorylation 1595:1609 intravirion kinase phosphorylation 1576:1609 intravirion kinase phosphorylation 1576:1609 Using isotopically enriched ATP, 23 sites of intravirion kinase phosphorylation were detected within nine virion proteins, all at sites already partially occupied within the virion preparations. 27558425 11 75 theme vaccinia 2041:2048 arg1 proteins 2056:2063 vaccinia virus proteins 2041:2063 vaccinia virus proteins 2041:2063 We provide evidence for the phosphoglycosylation of vaccinia virus proteins. 27558425 5 76 theme nicked 975:980 arg1 " 981:981 "nicked" 974:981 "nicked" 974:981 Evidence is provided that some portion of virion proteins are "nicked" via a combination of endoproteolysis and concerted exoproteolysis in a manner, and at sites, independent of virus origin or laboratory procedures. 27558425 5 76 theme nicked 975:980 arg1 portion 943:949 some portion 938:949 some portion of virion proteins 938:968 Evidence is provided that some portion of virion proteins are "nicked" via a combination of endoproteolysis and concerted exoproteolysis in a manner, and at sites, independent of virus origin or laboratory procedures. 27558425 6 77 dep 189 1200:1202 arg1 Ngo 1228:1230 Ngo 1228:1230 Ngo 1228:1230 The size of the characterized virion phosphoproteome was doubled from 189 (J. Matson, W. Chou, T. Ngo, and P. D. Gershon, Virology 452-453:310-323, 2014, doi:http://dx.doi.org/10.1016/j.virol.2014.01.012) to 396 confident, unique phosphorylation sites, 268 of which were within the packaged proteome. 27558425 6 77 dep 189 1200:1202 arg1 Virology 1252:1259 Virology 1252:1259 Virology 1252:1259 The size of the characterized virion phosphoproteome was doubled from 189 (J. Matson, W. Chou, T. Ngo, and P. D. Gershon, Virology 452-453:310-323, 2014, doi:http://dx.doi.org/10.1016/j.virol.2014.01.012) to 396 confident, unique phosphorylation sites, 268 of which were within the packaged proteome. 27558425 6 77 dep 189 1200:1202 arg1 T. 1225:1226 T. 1225:1226 T. 1225:1226 The size of the characterized virion phosphoproteome was doubled from 189 (J. Matson, W. Chou, T. Ngo, and P. D. Gershon, Virology 452-453:310-323, 2014, doi:http://dx.doi.org/10.1016/j.virol.2014.01.012) to 396 confident, unique phosphorylation sites, 268 of which were within the packaged proteome. 27558425 6 77 dep 189 1200:1202 arg1 Matson 1208:1213 Matson 1208:1213 Matson 1208:1213 The size of the characterized virion phosphoproteome was doubled from 189 (J. Matson, W. Chou, T. Ngo, and P. D. Gershon, Virology 452-453:310-323, 2014, doi:http://dx.doi.org/10.1016/j.virol.2014.01.012) to 396 confident, unique phosphorylation sites, 268 of which were within the packaged proteome. 27558425 6 77 dep 189 1200:1202 arg1 Gershon 1243:1249 Gershon 1243:1249 Gershon 1243:1249 The size of the characterized virion phosphoproteome was doubled from 189 (J. Matson, W. Chou, T. Ngo, and P. D. Gershon, Virology 452-453:310-323, 2014, doi:http://dx.doi.org/10.1016/j.virol.2014.01.012) to 396 confident, unique phosphorylation sites, 268 of which were within the packaged proteome. 27558425 8 78 theme phosphorylation 1595:1609 arg1 sites 1567:1571 23 sites 1564:1571 23 sites of intravirion kinase phosphorylation 1564:1609 Using isotopically enriched ATP, 23 sites of intravirion kinase phosphorylation were detected within nine virion proteins, all at sites already partially occupied within the virion preparations. 27558425 8 78 theme phosphorylation 1595:1609 arg1 phosphorylation 1595:1609 intravirion kinase phosphorylation 1576:1609 intravirion kinase phosphorylation 1576:1609 Using isotopically enriched ATP, 23 sites of intravirion kinase phosphorylation were detected within nine virion proteins, all at sites already partially occupied within the virion preparations. 27558425 14 79 theme spectrometry 2413:2424 arg1 tools 2386:2390 the various tools 2374:2390 the various tools of contemporary mass spectrometry 2374:2424 Here, we provide a deep study of the covalent structure of the vaccinia virus virion using the various tools of contemporary mass spectrometry. 27558425 12 80 theme internal 2150:2157 arg1 structure 2159:2167 structure 2159:2167 structure 2159:2167 IMPORTANCE Poxviruses are among the most complex and irregular virions, about whose internal structure little is known. 27558425 9 81 theme proteins 1818:1825 arg1 roles 1803:1807 the roles 1799:1807 the roles of these proteins in intravirion early gene transcription 1799:1865 The clear phosphorylation of proteins RAP94 and RP19 was consistent with the roles of these proteins in intravirion early gene transcription. 27558425 5 82 theme origin 1097:1102 arg1 independent 1076:1086 independent 1076:1086 independent 1076:1086 Evidence is provided that some portion of virion proteins are "nicked" via a combination of endoproteolysis and concerted exoproteolysis in a manner, and at sites, independent of virus origin or laboratory procedures. 27558425 1 83 theme reading 328:334 arg1 ORFs 344:347 ORFs 344:347 ORFs 344:347 Within two virion preparations, >88% of the theoretical vaccinia virus-encoded proteome was detected with high confidence, including the first detection of products from 27 open reading frames (ORFs) previously designated "predicted," "uncharacterized," "inferred," or "hypothetical" polypeptides containing as few as 39 amino acids (aa) and six proteins whose detection required nontryptic proteolysis. 27558425 1 83 theme reading 328:334 arg1 frames 336:341 27 open reading frames 320:341 27 open reading frames (ORFs) previously designated "predicted," "uncharacterized," "inferred," or "hypothetical" polypeptides containing as few as 39 amino acids (aa) and six proteins whose detection required nontryptic proteolysis 320:551 Within two virion preparations, >88% of the theoretical vaccinia virus-encoded proteome was detected with high confidence, including the first detection of products from 27 open reading frames (ORFs) previously designated "predicted," "uncharacterized," "inferred," or "hypothetical" polypeptides containing as few as 39 amino acids (aa) and six proteins whose detection required nontryptic proteolysis. 27558425 7 84 theme virion 1514:1519 arg1 proteins 1521:1528 virion proteins 1514:1528 virion proteins 1514:1528 This included the unambiguous identification of phosphorylation "hot spots" within virion proteins. 27558425 14 85 theme contemporary 2395:2406 arg1 spectrometry 2413:2424 contemporary mass spectrometry 2395:2424 contemporary mass spectrometry 2395:2424 Here, we provide a deep study of the covalent structure of the vaccinia virus virion using the various tools of contemporary mass spectrometry. 27558425 9 86 theme intravirion 1830:1840 arg1 transcription 1853:1865 intravirion early gene transcription 1830:1865 intravirion early gene transcription 1830:1865 The clear phosphorylation of proteins RAP94 and RP19 was consistent with the roles of these proteins in intravirion early gene transcription. 27558425 1 87 theme amino 471:475 arg1 aa 484:485 aa 484:485 aa 484:485 Within two virion preparations, >88% of the theoretical vaccinia virus-encoded proteome was detected with high confidence, including the first detection of products from 27 open reading frames (ORFs) previously designated "predicted," "uncharacterized," "inferred," or "hypothetical" polypeptides containing as few as 39 amino acids (aa) and six proteins whose detection required nontryptic proteolysis. 27558425 1 87 theme amino 471:475 arg1 acids 477:481 as few as 39 amino acids 458:481 as few as 39 amino acids (aa) 458:486 Within two virion preparations, >88% of the theoretical vaccinia virus-encoded proteome was detected with high confidence, including the first detection of products from 27 open reading frames (ORFs) previously designated "predicted," "uncharacterized," "inferred," or "hypothetical" polypeptides containing as few as 39 amino acids (aa) and six proteins whose detection required nontryptic proteolysis. 27558425 0 88 theme covalent 101:108 arg1 structure 110:118 the protein covalent structure 89:118 the protein covalent structure of the vaccinia virus virion 89:147 Protein Primary Structure of the Vaccinia Virion at Increased Resolution Here we examine the protein covalent structure of the vaccinia virus virion. 27558425 5 89 theme virion 954:959 arg1 proteins 961:968 virion proteins 954:968 virion proteins 954:968 Evidence is provided that some portion of virion proteins are "nicked" via a combination of endoproteolysis and concerted exoproteolysis in a manner, and at sites, independent of virus origin or laboratory procedures. 27558425 2 90 dep located 624:630 arg1 including 666:674 including 666:674 including one not previously recognized 666:704 We also detected the expression of four short ORFs, each of which was located within an ORF ("ORF-within-ORF"), including one not previously recognized or known to be expressed. 27558425 2 90 dep located 624:630 arg1 known 709:713 known 709:713 known to be expressed 709:729 We also detected the expression of four short ORFs, each of which was located within an ORF ("ORF-within-ORF"), including one not previously recognized or known to be expressed. 27558425 9 91 theme gene 1848:1851 arg1 transcription 1853:1865 intravirion early gene transcription 1830:1865 intravirion early gene transcription 1830:1865 The clear phosphorylation of proteins RAP94 and RP19 was consistent with the roles of these proteins in intravirion early gene transcription. 27558425 0 92 theme Primary 8:14 arg1 Structure 16:24 Protein Primary Structure 0:24 Protein Primary Structure of the Vaccinia Virion at Increased Resolution 0:71 Protein Primary Structure of the Vaccinia Virion at Increased Resolution Here we examine the protein covalent structure of the vaccinia virus virion. 27558425 6 93 theme packaged 1412:1419 arg1 proteome 1421:1428 the packaged proteome 1408:1428 the packaged proteome 1408:1428 The size of the characterized virion phosphoproteome was doubled from 189 (J. Matson, W. Chou, T. Ngo, and P. D. Gershon, Virology 452-453:310-323, 2014, doi:http://dx.doi.org/10.1016/j.virol.2014.01.012) to 396 confident, unique phosphorylation sites, 268 of which were within the packaged proteome. 27558425 7 94 theme hot 1496:1498 arg1 spots 1500:1504 phosphorylation "hot spots 1479:1504 phosphorylation "hot spots" within virion proteins 1479:1528 This included the unambiguous identification of phosphorylation "hot spots" within virion proteins. 27558425 0 95 theme vaccinia 127:134 arg1 virion 142:147 the vaccinia virus virion 123:147 the vaccinia virus virion 123:147 Protein Primary Structure of the Vaccinia Virion at Increased Resolution Here we examine the protein covalent structure of the vaccinia virus virion. 27558425 2 96 theme short 594:598 arg1 ORFs 600:603 four short ORFs 589:603 four short ORFs 589:603 We also detected the expression of four short ORFs, each of which was located within an ORF ("ORF-within-ORF"), including one not previously recognized or known to be expressed. 27558425 1 97 from frames 336:341 arg1 detection 293:301 the first detection 283:301 the first detection of products from 27 open reading frames (ORFs) previously designated "predicted," "uncharacterized," "inferred," or "hypothetical" polypeptides containing as few as 39 amino acids (aa) and six proteins whose detection required nontryptic proteolysis 283:551 Within two virion preparations, >88% of the theoretical vaccinia virus-encoded proteome was detected with high confidence, including the first detection of products from 27 open reading frames (ORFs) previously designated "predicted," "uncharacterized," "inferred," or "hypothetical" polypeptides containing as few as 39 amino acids (aa) and six proteins whose detection required nontryptic proteolysis. 27558425 1 97 from frames 336:341 arg1 products 306:313 products 306:313 products from 27 open reading frames (ORFs) previously designated "predicted," "uncharacterized," "inferred," or "hypothetical" polypeptides containing as few as 39 amino acids (aa) and six proteins whose detection required nontryptic proteolysis 306:551 Within two virion preparations, >88% of the theoretical vaccinia virus-encoded proteome was detected with high confidence, including the first detection of products from 27 open reading frames (ORFs) previously designated "predicted," "uncharacterized," "inferred," or "hypothetical" polypeptides containing as few as 39 amino acids (aa) and six proteins whose detection required nontryptic proteolysis. 27558425 5 98 theme concerted 1024:1032 arg1 exoproteolysis 1034:1047 concerted exoproteolysis 1024:1047 concerted exoproteolysis 1024:1047 Evidence is provided that some portion of virion proteins are "nicked" via a combination of endoproteolysis and concerted exoproteolysis in a manner, and at sites, independent of virus origin or laboratory procedures. 27558425 7 99 theme phosphorylation 1479:1493 arg1 spots 1500:1504 phosphorylation "hot spots 1479:1504 phosphorylation "hot spots" within virion proteins 1479:1528 This included the unambiguous identification of phosphorylation "hot spots" within virion proteins. 27558425 12 100 theme IMPORTANCE 2066:2075 arg1 Poxviruses 2077:2086 IMPORTANCE Poxviruses 2066:2086 IMPORTANCE Poxviruses 2066:2086 IMPORTANCE Poxviruses are among the most complex and irregular virions, about whose internal structure little is known. 27558425 5 101 from " 981:981 arg1 manner 1054:1059 a manner 1052:1059 a manner 1052:1059 Evidence is provided that some portion of virion proteins are "nicked" via a combination of endoproteolysis and concerted exoproteolysis in a manner, and at sites, independent of virus origin or laboratory procedures. 27558425 14 102 theme various 2378:2384 arg1 tools 2386:2390 the various tools 2374:2390 the various tools of contemporary mass spectrometry 2374:2424 Here, we provide a deep study of the covalent structure of the vaccinia virus virion using the various tools of contemporary mass spectrometry. 27558425 4 103 theme host 848:851 arg1 proteins 853:860 63 host proteins 845:860 63 host proteins 845:860 A total of 63 host proteins were also identified as candidates for packaging. 27558425 1 104 theme hypothetical 420:431 arg1 polypeptides 434:445 "hypothetical" polypeptides 419:445 "hypothetical" polypeptides 419:445 Within two virion preparations, >88% of the theoretical vaccinia virus-encoded proteome was detected with high confidence, including the first detection of products from 27 open reading frames (ORFs) previously designated "predicted," "uncharacterized," "inferred," or "hypothetical" polypeptides containing as few as 39 amino acids (aa) and six proteins whose detection required nontryptic proteolysis. 27558425 6 105 dep Matson 1208:1213 arg1 http 1288:1291 http 1288:1291 http://dx.doi.org/10.1016/j.virol.2014.01.012 1288:1332 The size of the characterized virion phosphoproteome was doubled from 189 (J. Matson, W. Chou, T. Ngo, and P. D. Gershon, Virology 452-453:310-323, 2014, doi:http://dx.doi.org/10.1016/j.virol.2014.01.012) to 396 confident, unique phosphorylation sites, 268 of which were within the packaged proteome. 27558425 6 105 dep Matson 1208:1213 arg1 doi 1284:1286 doi 1284:1286 doi 1284:1286 The size of the characterized virion phosphoproteome was doubled from 189 (J. Matson, W. Chou, T. Ngo, and P. D. Gershon, Virology 452-453:310-323, 2014, doi:http://dx.doi.org/10.1016/j.virol.2014.01.012) to 396 confident, unique phosphorylation sites, 268 of which were within the packaged proteome. 27558425 5 106 theme endoproteolysis 1004:1018 arg1 combination 989:999 a combination 987:999 a combination of endoproteolysis and concerted exoproteolysis 987:1047 Evidence is provided that some portion of virion proteins are "nicked" via a combination of endoproteolysis and concerted exoproteolysis in a manner, and at sites, independent of virus origin or laboratory procedures. 27558425 14 107 theme virus 2355:2359 arg1 virion 2361:2366 the vaccinia virus virion 2342:2366 the vaccinia virus virion 2342:2366 Here, we provide a deep study of the covalent structure of the vaccinia virus virion using the various tools of contemporary mass spectrometry. 27558425 1 108 located detected 242:249 arg1 preparations 168:179 two virion preparations 157:179 two virion preparations 157:179 Within two virion preparations, >88% of the theoretical vaccinia virus-encoded proteome was detected with high confidence, including the first detection of products from 27 open reading frames (ORFs) previously designated "predicted," "uncharacterized," "inferred," or "hypothetical" polypeptides containing as few as 39 amino acids (aa) and six proteins whose detection required nontryptic proteolysis. 27558425 1 108 located detected 242:249 arg2 % 185:185 >88% 182:185 >88% of the theoretical vaccinia virus-encoded proteome 182:236 Within two virion preparations, >88% of the theoretical vaccinia virus-encoded proteome was detected with high confidence, including the first detection of products from 27 open reading frames (ORFs) previously designated "predicted," "uncharacterized," "inferred," or "hypothetical" polypeptides containing as few as 39 amino acids (aa) and six proteins whose detection required nontryptic proteolysis. 27558425 1 108 located detected 242:249 arg2 proteome 229:236 the theoretical vaccinia virus-encoded proteome 190:236 the theoretical vaccinia virus-encoded proteome 190:236 Within two virion preparations, >88% of the theoretical vaccinia virus-encoded proteome was detected with high confidence, including the first detection of products from 27 open reading frames (ORFs) previously designated "predicted," "uncharacterized," "inferred," or "hypothetical" polypeptides containing as few as 39 amino acids (aa) and six proteins whose detection required nontryptic proteolysis. 27558425 11 109 gly phosphoglycosylation 2017:2036 arg1 proteins 2056:2063 vaccinia virus proteins 2041:2063 vaccinia virus proteins 2041:2063 We provide evidence for the phosphoglycosylation of vaccinia virus proteins. 27558425 1 110 theme vaccinia 206:213 arg1 proteome 229:236 the theoretical vaccinia virus-encoded proteome 190:236 the theoretical vaccinia virus-encoded proteome 190:236 Within two virion preparations, >88% of the theoretical vaccinia virus-encoded proteome was detected with high confidence, including the first detection of products from 27 open reading frames (ORFs) previously designated "predicted," "uncharacterized," "inferred," or "hypothetical" polypeptides containing as few as 39 amino acids (aa) and six proteins whose detection required nontryptic proteolysis. 27558425 1 111 theme proteome 229:236 arg1 % 185:185 >88% 182:185 >88% of the theoretical vaccinia virus-encoded proteome 182:236 Within two virion preparations, >88% of the theoretical vaccinia virus-encoded proteome was detected with high confidence, including the first detection of products from 27 open reading frames (ORFs) previously designated "predicted," "uncharacterized," "inferred," or "hypothetical" polypeptides containing as few as 39 amino acids (aa) and six proteins whose detection required nontryptic proteolysis. 27558425 1 111 theme proteome 229:236 arg1 proteome 229:236 the theoretical vaccinia virus-encoded proteome 190:236 the theoretical vaccinia virus-encoded proteome 190:236 Within two virion preparations, >88% of the theoretical vaccinia virus-encoded proteome was detected with high confidence, including the first detection of products from 27 open reading frames (ORFs) previously designated "predicted," "uncharacterized," "inferred," or "hypothetical" polypeptides containing as few as 39 amino acids (aa) and six proteins whose detection required nontryptic proteolysis. 27131860 12 0 theme H. 1807:1808 arg1 gastritis 1834:1842 H. pylori-infected chronic gastritis 1807:1842 H. pylori-infected chronic gastritis 1807:1842 In addition, the expression of O-GlcNAcylation and OGT was more elevated in H. pylori-infected chronic gastritis than in chronic gastritis without H. pylori infection. 27131860 11 1 theme O-GlcNAcylation 1562:1576 arg1 expression 1578:1587 Nuclear O-GlcNAcylation expression 1554:1587 Nuclear O-GlcNAcylation expression in GC 1554:1593 Nuclear O-GlcNAcylation expression in GC was closely associated with large size, moderate and poor differentiation, higher pT stage, nodal metastasis and higher clinical stage. 27131860 11 2 theme nodal 1687:1691 arg1 metastasis 1693:1702 nodal metastasis 1687:1702 nodal metastasis 1687:1702 Nuclear O-GlcNAcylation expression in GC was closely associated with large size, moderate and poor differentiation, higher pT stage, nodal metastasis and higher clinical stage. 27131860 10 3 theme Nuclear 1374:1380 arg1 expression 1398:1407 Nuclear O-GlcNAcylation expression 1374:1407 Nuclear O-GlcNAcylation expression 1374:1407 Nuclear O-GlcNAcylation expression was more frequently observed in tumors including GC and adenoma than in nonneoplastic tissues including intestinal metaplasia and normal tissue. 27131860 4 4 theme Helicobacter 823:834 arg1 pylori 836:841 Helicobacter pylori 823:841 Helicobacter pylori (H. pylori) infection 823:863 Their expressions were also studied in 20 tissues of chronic gastritis according to Helicobacter pylori (H. pylori) infection. 27131860 4 4 theme Helicobacter 823:834 arg1 H. 844:845 H. 844:845 H. 844:845 Their expressions were also studied in 20 tissues of chronic gastritis according to Helicobacter pylori (H. pylori) infection. 27131860 1 5 attach linked 181:186 arg2 moiety 174:179 an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety 129:179 an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety linked to the side chain hydroxyl of a serine or threonine residue on nucleocytoplasmic proteins 129:276 INTRODUCTION O-GlcNAcylation occurs via an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety linked to the side chain hydroxyl of a serine or threonine residue on nucleocytoplasmic proteins. 27131860 1 5 attach linked 181:186 arg1 hydroxyl 206:213 the side chain hydroxyl 191:213 the side chain hydroxyl of a serine or threonine residue on nucleocytoplasmic proteins 191:276 INTRODUCTION O-GlcNAcylation occurs via an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety linked to the side chain hydroxyl of a serine or threonine residue on nucleocytoplasmic proteins. 27131860 3 6 theme Immunohistochemical 509:527 arg1 staining 529:536 MATERIALS AND METHODS Immunohistochemical staining 487:536 MATERIALS AND METHODS Immunohistochemical staining for O-GlcNAcylation and OGT 487:564 MATERIALS AND METHODS Immunohistochemical staining for O-GlcNAcylation and OGT was performed in 64 primary GCs, 40 gastric adenomas and nonneoplastic tissues adjacent to GCs, including 31 tissues of intestinal metaplasia and 24 normal gastric tissues. 27131860 1 7 theme chain 200:204 arg1 hydroxyl 206:213 the side chain hydroxyl 191:213 the side chain hydroxyl of a serine or threonine residue on nucleocytoplasmic proteins 191:276 INTRODUCTION O-GlcNAcylation occurs via an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety linked to the side chain hydroxyl of a serine or threonine residue on nucleocytoplasmic proteins. 27131860 8 8 theme GC 1205:1206 arg1 carcinogenesis 1187:1200 the carcinogenesis 1183:1200 the carcinogenesis of GC 1183:1206 Their expression levels were progressively increased during the carcinogenesis of GC. 27131860 3 9 theme normal 715:720 arg1 tissues 730:736 24 normal gastric tissues 712:736 24 normal gastric tissues 712:736 MATERIALS AND METHODS Immunohistochemical staining for O-GlcNAcylation and OGT was performed in 64 primary GCs, 40 gastric adenomas and nonneoplastic tissues adjacent to GCs, including 31 tissues of intestinal metaplasia and 24 normal gastric tissues. 27131860 7 10 theme expression 1056:1065 arg1 levels 1067:1072 O-GlcNAcylation expression levels 1040:1072 O-GlcNAcylation expression levels 1040:1072 O-GlcNAcylation expression levels were significantly correlated with those of OGT. 27131860 1 11 from proteins 269:276 arg1 hydroxyl 206:213 the side chain hydroxyl 191:213 the side chain hydroxyl of a serine or threonine residue on nucleocytoplasmic proteins 191:276 INTRODUCTION O-GlcNAcylation occurs via an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety linked to the side chain hydroxyl of a serine or threonine residue on nucleocytoplasmic proteins. 27131860 3 12 theme primary 586:592 arg1 tissues 730:736 24 normal gastric tissues 712:736 24 normal gastric tissues 712:736 MATERIALS AND METHODS Immunohistochemical staining for O-GlcNAcylation and OGT was performed in 64 primary GCs, 40 gastric adenomas and nonneoplastic tissues adjacent to GCs, including 31 tissues of intestinal metaplasia and 24 normal gastric tissues. 27131860 3 12 theme primary 586:592 arg1 tissues 675:681 31 tissues 672:681 31 tissues of intestinal metaplasia 672:706 MATERIALS AND METHODS Immunohistochemical staining for O-GlcNAcylation and OGT was performed in 64 primary GCs, 40 gastric adenomas and nonneoplastic tissues adjacent to GCs, including 31 tissues of intestinal metaplasia and 24 normal gastric tissues. 27131860 3 12 theme primary 586:592 arg1 GCs 594:596 64 primary GCs 583:596 64 primary GCs 583:596 MATERIALS AND METHODS Immunohistochemical staining for O-GlcNAcylation and OGT was performed in 64 primary GCs, 40 gastric adenomas and nonneoplastic tissues adjacent to GCs, including 31 tissues of intestinal metaplasia and 24 normal gastric tissues. 27131860 1 13 theme serine 220:225 arg1 residue 240:246 a serine or threonine residue 218:246 residue 240:246 INTRODUCTION O-GlcNAcylation occurs via an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety linked to the side chain hydroxyl of a serine or threonine residue on nucleocytoplasmic proteins. 27131860 9 14 theme intestinal 1258:1267 arg1 type 1269:1272 intestinal type 1258:1272 intestinal type 1258:1272 O-GlcNAcylation expression was higher in GC with intestinal type, higher pT stage and nodal metastasis, while OGT expression was higher in GC with nodal metastasis. 27131860 1 15 from hydroxyl 206:213 arg1 proteins 269:276 nucleocytoplasmic proteins 251:276 nucleocytoplasmic proteins 251:276 INTRODUCTION O-GlcNAcylation occurs via an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety linked to the side chain hydroxyl of a serine or threonine residue on nucleocytoplasmic proteins. 27131860 1 16 theme O-linked 132:139 arg1 moiety 174:179 an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety 129:179 an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety linked to the side chain hydroxyl of a serine or threonine residue on nucleocytoplasmic proteins 129:276 INTRODUCTION O-GlcNAcylation occurs via an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety linked to the side chain hydroxyl of a serine or threonine residue on nucleocytoplasmic proteins. 27131860 3 17 theme gastric 602:608 arg1 tissues 730:736 24 normal gastric tissues 712:736 24 normal gastric tissues 712:736 MATERIALS AND METHODS Immunohistochemical staining for O-GlcNAcylation and OGT was performed in 64 primary GCs, 40 gastric adenomas and nonneoplastic tissues adjacent to GCs, including 31 tissues of intestinal metaplasia and 24 normal gastric tissues. 27131860 3 17 theme gastric 602:608 arg1 tissues 675:681 31 tissues 672:681 31 tissues of intestinal metaplasia 672:706 MATERIALS AND METHODS Immunohistochemical staining for O-GlcNAcylation and OGT was performed in 64 primary GCs, 40 gastric adenomas and nonneoplastic tissues adjacent to GCs, including 31 tissues of intestinal metaplasia and 24 normal gastric tissues. 27131860 3 17 theme gastric 602:608 arg1 adenomas 610:617 40 gastric adenomas 599:617 40 gastric adenomas 599:617 MATERIALS AND METHODS Immunohistochemical staining for O-GlcNAcylation and OGT was performed in 64 primary GCs, 40 gastric adenomas and nonneoplastic tissues adjacent to GCs, including 31 tissues of intestinal metaplasia and 24 normal gastric tissues. 27131860 9 18 theme pT 1282:1283 arg1 stage 1285:1289 higher pT stage 1275:1289 higher pT stage 1275:1289 O-GlcNAcylation expression was higher in GC with intestinal type, higher pT stage and nodal metastasis, while OGT expression was higher in GC with nodal metastasis. 27131860 5 19 theme RESULTS 866:872 arg1 O-GlcNAcylation 874:888 RESULTS O-GlcNAcylation 866:888 RESULTS O-GlcNAcylation 866:888 RESULTS O-GlcNAcylation was expressed in the nucleus and both the nuclear rim and cytoplasm. 27131860 13 20 dep carcinogenesis 1990:2003 arg1 the 1986:1988 the 1986:1988 the 1986:1988 CONCLUSIONS O-GlcNAcylation expression and its nuclear expression were associated with the carcinogenesis and progression of GC. 27131860 2 21 from significance 409:420 arg1 GC 445:446 GC 445:446 GC 445:446 This reaction, which is catalyzed by O-GlcNAc-transferase (OGT), is involved in a variety of human cancers; however, its clinical significance in gastric carcinomas (GC) has been poorly investigated in vivo. 27131860 2 21 from significance 409:420 arg1 carcinomas 433:442 gastric carcinomas 425:442 gastric carcinomas (GC) 425:447 This reaction, which is catalyzed by O-GlcNAc-transferase (OGT), is involved in a variety of human cancers; however, its clinical significance in gastric carcinomas (GC) has been poorly investigated in vivo. 27131860 0 22 theme carcinoma 78:86 arg1 development 39:49 development 39:49 development 39:49 O-GlcNAcylation is associated with the development and progression of gastric carcinoma. 27131860 0 22 theme carcinoma 78:86 arg1 progression 55:65 progression 55:65 progression 55:65 O-GlcNAcylation is associated with the development and progression of gastric carcinoma. 27131860 11 23 from expression 1578:1587 arg1 GC 1592:1593 GC 1592:1593 GC 1592:1593 Nuclear O-GlcNAcylation expression in GC was closely associated with large size, moderate and poor differentiation, higher pT stage, nodal metastasis and higher clinical stage. 27131860 3 24 theme nonneoplastic 623:635 arg1 tissues 730:736 24 normal gastric tissues 712:736 24 normal gastric tissues 712:736 MATERIALS AND METHODS Immunohistochemical staining for O-GlcNAcylation and OGT was performed in 64 primary GCs, 40 gastric adenomas and nonneoplastic tissues adjacent to GCs, including 31 tissues of intestinal metaplasia and 24 normal gastric tissues. 27131860 3 24 theme nonneoplastic 623:635 arg1 tissues 675:681 31 tissues 672:681 31 tissues of intestinal metaplasia 672:706 MATERIALS AND METHODS Immunohistochemical staining for O-GlcNAcylation and OGT was performed in 64 primary GCs, 40 gastric adenomas and nonneoplastic tissues adjacent to GCs, including 31 tissues of intestinal metaplasia and 24 normal gastric tissues. 27131860 3 24 theme nonneoplastic 623:635 arg1 tissues 637:643 nonneoplastic tissues 623:643 nonneoplastic tissues 623:643 MATERIALS AND METHODS Immunohistochemical staining for O-GlcNAcylation and OGT was performed in 64 primary GCs, 40 gastric adenomas and nonneoplastic tissues adjacent to GCs, including 31 tissues of intestinal metaplasia and 24 normal gastric tissues. 27131860 13 25 theme GC 2024:2025 arg1 carcinogenesis 1990:2003 carcinogenesis 1990:2003 carcinogenesis 1990:2003 CONCLUSIONS O-GlcNAcylation expression and its nuclear expression were associated with the carcinogenesis and progression of GC. 27131860 13 25 theme GC 2024:2025 arg1 progression 2009:2019 progression 2009:2019 progression 2009:2019 CONCLUSIONS O-GlcNAcylation expression and its nuclear expression were associated with the carcinogenesis and progression of GC. 27131860 13 26 theme CONCLUSIONS 1899:1909 arg1 expression 1927:1936 CONCLUSIONS O-GlcNAcylation expression 1899:1936 CONCLUSIONS O-GlcNAcylation expression 1899:1936 CONCLUSIONS O-GlcNAcylation expression and its nuclear expression were associated with the carcinogenesis and progression of GC. 27131860 2 27 theme human 372:376 arg1 cancers 378:384 human cancers 372:384 human cancers 372:384 This reaction, which is catalyzed by O-GlcNAc-transferase (OGT), is involved in a variety of human cancers; however, its clinical significance in gastric carcinomas (GC) has been poorly investigated in vivo. 27131860 10 28 theme intestinal 1513:1522 arg1 metaplasia 1524:1533 intestinal metaplasia 1513:1533 intestinal metaplasia 1513:1533 Nuclear O-GlcNAcylation expression was more frequently observed in tumors including GC and adenoma than in nonneoplastic tissues including intestinal metaplasia and normal tissue. 27131860 2 29 theme clinical 400:407 arg1 significance 409:420 its clinical significance 396:420 its clinical significance in gastric carcinomas (GC) 396:447 This reaction, which is catalyzed by O-GlcNAc-transferase (OGT), is involved in a variety of human cancers; however, its clinical significance in gastric carcinomas (GC) has been poorly investigated in vivo. 27131860 12 30 theme pylori 1881:1886 arg1 infection 1888:1896 H. pylori infection 1878:1896 H. pylori infection 1878:1896 In addition, the expression of O-GlcNAcylation and OGT was more elevated in H. pylori-infected chronic gastritis than in chronic gastritis without H. pylori infection. 27131860 5 31 theme nuclear 932:938 arg1 rim 940:942 the nuclear rim 928:942 the nuclear rim 928:942 RESULTS O-GlcNAcylation was expressed in the nucleus and both the nuclear rim and cytoplasm. 27131860 4 32 theme chronic 792:798 arg1 gastritis 800:808 chronic gastritis 792:808 chronic gastritis 792:808 Their expressions were also studied in 20 tissues of chronic gastritis according to Helicobacter pylori (H. pylori) infection. 27131860 11 33 theme higher 1708:1713 arg1 stage 1724:1728 higher clinical stage 1708:1728 higher clinical stage 1708:1728 Nuclear O-GlcNAcylation expression in GC was closely associated with large size, moderate and poor differentiation, higher pT stage, nodal metastasis and higher clinical stage. 27131860 3 34 theme intestinal 686:695 arg1 metaplasia 697:706 intestinal metaplasia 686:706 intestinal metaplasia 686:706 MATERIALS AND METHODS Immunohistochemical staining for O-GlcNAcylation and OGT was performed in 64 primary GCs, 40 gastric adenomas and nonneoplastic tissues adjacent to GCs, including 31 tissues of intestinal metaplasia and 24 normal gastric tissues. 27131860 4 35 dep H. 844:845 arg1 pylori 847:852 H. pylori 844:852 H. pylori 844:852 Their expressions were also studied in 20 tissues of chronic gastritis according to Helicobacter pylori (H. pylori) infection. 27131860 9 36 theme nodal 1356:1360 arg1 metastasis 1362:1371 nodal metastasis 1356:1371 nodal metastasis 1356:1371 O-GlcNAcylation expression was higher in GC with intestinal type, higher pT stage and nodal metastasis, while OGT expression was higher in GC with nodal metastasis. 27131860 12 37 theme chronic 1852:1858 arg1 gastritis 1860:1868 chronic gastritis 1852:1868 chronic gastritis 1852:1868 In addition, the expression of O-GlcNAcylation and OGT was more elevated in H. pylori-infected chronic gastritis than in chronic gastritis without H. pylori infection. 27131860 10 38 located observed 1429:1436 arg1 tumors 1441:1446 tumors 1441:1446 tumors including GC and adenoma 1441:1471 Nuclear O-GlcNAcylation expression was more frequently observed in tumors including GC and adenoma than in nonneoplastic tissues including intestinal metaplasia and normal tissue. 27131860 10 38 located observed 1429:1436 arg1 tissue 1546:1551 normal tissue 1539:1551 normal tissue 1539:1551 Nuclear O-GlcNAcylation expression was more frequently observed in tumors including GC and adenoma than in nonneoplastic tissues including intestinal metaplasia and normal tissue. 27131860 10 38 located observed 1429:1436 arg1 GC 1458:1459 GC 1458:1459 GC 1458:1459 Nuclear O-GlcNAcylation expression was more frequently observed in tumors including GC and adenoma than in nonneoplastic tissues including intestinal metaplasia and normal tissue. 27131860 10 38 located observed 1429:1436 arg1 tissues 1495:1501 nonneoplastic tissues 1481:1501 nonneoplastic tissues including intestinal metaplasia and normal tissue 1481:1551 Nuclear O-GlcNAcylation expression was more frequently observed in tumors including GC and adenoma than in nonneoplastic tissues including intestinal metaplasia and normal tissue. 27131860 10 38 located observed 1429:1436 arg2 expression 1398:1407 Nuclear O-GlcNAcylation expression 1374:1407 Nuclear O-GlcNAcylation expression 1374:1407 Nuclear O-GlcNAcylation expression was more frequently observed in tumors including GC and adenoma than in nonneoplastic tissues including intestinal metaplasia and normal tissue. 27131860 10 38 located observed 1429:1436 arg1 adenoma 1465:1471 adenoma 1465:1471 adenoma 1465:1471 Nuclear O-GlcNAcylation expression was more frequently observed in tumors including GC and adenoma than in nonneoplastic tissues including intestinal metaplasia and normal tissue. 27131860 10 38 located observed 1429:1436 arg1 metaplasia 1524:1533 intestinal metaplasia 1513:1533 intestinal metaplasia 1513:1533 Nuclear O-GlcNAcylation expression was more frequently observed in tumors including GC and adenoma than in nonneoplastic tissues including intestinal metaplasia and normal tissue. 27131860 11 39 theme poor 1648:1651 arg1 differentiation 1653:1667 moderate and poor differentiation 1635:1667 moderate and poor differentiation 1635:1667 Nuclear O-GlcNAcylation expression in GC was closely associated with large size, moderate and poor differentiation, higher pT stage, nodal metastasis and higher clinical stage. 27131860 3 40 theme MATERIALS 487:495 arg1 staining 529:536 MATERIALS AND METHODS Immunohistochemical staining 487:536 MATERIALS AND METHODS Immunohistochemical staining for O-GlcNAcylation and OGT 487:564 MATERIALS AND METHODS Immunohistochemical staining for O-GlcNAcylation and OGT was performed in 64 primary GCs, 40 gastric adenomas and nonneoplastic tissues adjacent to GCs, including 31 tissues of intestinal metaplasia and 24 normal gastric tissues. 27131860 1 41 theme residue 240:246 arg1 hydroxyl 206:213 the side chain hydroxyl 191:213 the side chain hydroxyl of a serine or threonine residue on nucleocytoplasmic proteins 191:276 INTRODUCTION O-GlcNAcylation occurs via an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety linked to the side chain hydroxyl of a serine or threonine residue on nucleocytoplasmic proteins. 27131860 12 42 theme pylori-infected 1810:1824 arg1 gastritis 1834:1842 H. pylori-infected chronic gastritis 1807:1842 H. pylori-infected chronic gastritis 1807:1842 In addition, the expression of O-GlcNAcylation and OGT was more elevated in H. pylori-infected chronic gastritis than in chronic gastritis without H. pylori infection. 27131860 11 43 theme pT 1677:1678 arg1 stage 1680:1684 higher pT stage 1670:1684 higher pT stage 1670:1684 Nuclear O-GlcNAcylation expression in GC was closely associated with large size, moderate and poor differentiation, higher pT stage, nodal metastasis and higher clinical stage. 27131860 11 44 theme moderate 1635:1642 arg1 differentiation 1653:1667 moderate and poor differentiation 1635:1667 moderate and poor differentiation 1635:1667 Nuclear O-GlcNAcylation expression in GC was closely associated with large size, moderate and poor differentiation, higher pT stage, nodal metastasis and higher clinical stage. 27131860 1 45 theme nucleocytoplasmic 251:267 arg1 proteins 269:276 nucleocytoplasmic proteins 251:276 nucleocytoplasmic proteins 251:276 INTRODUCTION O-GlcNAcylation occurs via an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety linked to the side chain hydroxyl of a serine or threonine residue on nucleocytoplasmic proteins. 27131860 8 46 theme expression 1129:1138 arg1 levels 1140:1145 Their expression levels 1123:1145 Their expression levels 1123:1145 Their expression levels were progressively increased during the carcinogenesis of GC. 27131860 12 47 theme OGT 1782:1784 arg1 elevated 1795:1802 elevated 1795:1802 elevated 1795:1802 In addition, the expression of O-GlcNAcylation and OGT was more elevated in H. pylori-infected chronic gastritis than in chronic gastritis without H. pylori infection. 27131860 12 47 theme OGT 1782:1784 arg1 expression 1748:1757 the expression 1744:1757 the expression of O-GlcNAcylation and OGT 1744:1784 In addition, the expression of O-GlcNAcylation and OGT was more elevated in H. pylori-infected chronic gastritis than in chronic gastritis without H. pylori infection. 27131860 12 48 from elevated 1795:1802 arg1 gastritis 1834:1842 H. pylori-infected chronic gastritis 1807:1842 H. pylori-infected chronic gastritis 1807:1842 In addition, the expression of O-GlcNAcylation and OGT was more elevated in H. pylori-infected chronic gastritis than in chronic gastritis without H. pylori infection. 27131860 12 48 from elevated 1795:1802 arg1 addition 1734:1741 addition 1734:1741 addition 1734:1741 In addition, the expression of O-GlcNAcylation and OGT was more elevated in H. pylori-infected chronic gastritis than in chronic gastritis without H. pylori infection. 27131860 12 48 from elevated 1795:1802 arg1 gastritis 1860:1868 chronic gastritis 1852:1868 chronic gastritis 1852:1868 In addition, the expression of O-GlcNAcylation and OGT was more elevated in H. pylori-infected chronic gastritis than in chronic gastritis without H. pylori infection. 27131860 10 49 theme O-GlcNAcylation 1382:1396 arg1 expression 1398:1407 Nuclear O-GlcNAcylation expression 1374:1407 Nuclear O-GlcNAcylation expression 1374:1407 Nuclear O-GlcNAcylation expression was more frequently observed in tumors including GC and adenoma than in nonneoplastic tissues including intestinal metaplasia and normal tissue. 27131860 11 50 theme Nuclear 1554:1560 arg1 expression 1578:1587 Nuclear O-GlcNAcylation expression 1554:1587 Nuclear O-GlcNAcylation expression in GC 1554:1593 Nuclear O-GlcNAcylation expression in GC was closely associated with large size, moderate and poor differentiation, higher pT stage, nodal metastasis and higher clinical stage. 27131860 3 51 theme METHODS 501:507 arg1 staining 529:536 MATERIALS AND METHODS Immunohistochemical staining 487:536 MATERIALS AND METHODS Immunohistochemical staining for O-GlcNAcylation and OGT 487:564 MATERIALS AND METHODS Immunohistochemical staining for O-GlcNAcylation and OGT was performed in 64 primary GCs, 40 gastric adenomas and nonneoplastic tissues adjacent to GCs, including 31 tissues of intestinal metaplasia and 24 normal gastric tissues. 27131860 3 52 theme metaplasia 697:706 arg1 tissues 675:681 31 tissues 672:681 31 tissues of intestinal metaplasia 672:706 MATERIALS AND METHODS Immunohistochemical staining for O-GlcNAcylation and OGT was performed in 64 primary GCs, 40 gastric adenomas and nonneoplastic tissues adjacent to GCs, including 31 tissues of intestinal metaplasia and 24 normal gastric tissues. 27131860 3 52 theme metaplasia 697:706 arg1 tissues 730:736 24 normal gastric tissues 712:736 24 normal gastric tissues 712:736 MATERIALS AND METHODS Immunohistochemical staining for O-GlcNAcylation and OGT was performed in 64 primary GCs, 40 gastric adenomas and nonneoplastic tissues adjacent to GCs, including 31 tissues of intestinal metaplasia and 24 normal gastric tissues. 27131860 9 53 theme O-GlcNAcylation 1209:1223 arg1 expression 1225:1234 O-GlcNAcylation expression 1209:1234 O-GlcNAcylation expression 1209:1234 O-GlcNAcylation expression was higher in GC with intestinal type, higher pT stage and nodal metastasis, while OGT expression was higher in GC with nodal metastasis. 27131860 1 54 theme side 195:198 arg1 chain 200:204 the side chain 191:204 the side chain hydroxyl of a serine or threonine residue on nucleocytoplasmic proteins 191:276 INTRODUCTION O-GlcNAcylation occurs via an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety linked to the side chain hydroxyl of a serine or threonine residue on nucleocytoplasmic proteins. 27131860 4 55 theme pylori 836:841 arg1 infection 855:863 Helicobacter pylori (H. pylori) infection 823:863 Helicobacter pylori (H. pylori) infection 823:863 Their expressions were also studied in 20 tissues of chronic gastritis according to Helicobacter pylori (H. pylori) infection. 27131860 12 56 theme O-GlcNAcylation 1762:1776 arg1 elevated 1795:1802 elevated 1795:1802 elevated 1795:1802 In addition, the expression of O-GlcNAcylation and OGT was more elevated in H. pylori-infected chronic gastritis than in chronic gastritis without H. pylori infection. 27131860 12 56 theme O-GlcNAcylation 1762:1776 arg1 expression 1748:1757 the expression 1744:1757 the expression of O-GlcNAcylation and OGT 1744:1784 In addition, the expression of O-GlcNAcylation and OGT was more elevated in H. pylori-infected chronic gastritis than in chronic gastritis without H. pylori infection. 27131860 7 57 theme O-GlcNAcylation 1040:1054 arg1 levels 1067:1072 O-GlcNAcylation expression levels 1040:1072 O-GlcNAcylation expression levels 1040:1072 O-GlcNAcylation expression levels were significantly correlated with those of OGT. 27131860 3 58 theme gastric 722:728 arg1 tissues 730:736 24 normal gastric tissues 712:736 24 normal gastric tissues 712:736 MATERIALS AND METHODS Immunohistochemical staining for O-GlcNAcylation and OGT was performed in 64 primary GCs, 40 gastric adenomas and nonneoplastic tissues adjacent to GCs, including 31 tissues of intestinal metaplasia and 24 normal gastric tissues. 27131860 12 59 from addition 1734:1741 arg1 elevated 1795:1802 elevated 1795:1802 elevated 1795:1802 In addition, the expression of O-GlcNAcylation and OGT was more elevated in H. pylori-infected chronic gastritis than in chronic gastritis without H. pylori infection. 27131860 12 59 from addition 1734:1741 arg1 expression 1748:1757 the expression 1744:1757 the expression of O-GlcNAcylation and OGT 1744:1784 In addition, the expression of O-GlcNAcylation and OGT was more elevated in H. pylori-infected chronic gastritis than in chronic gastritis without H. pylori infection. 27131860 1 60 from residue 240:246 arg1 proteins 269:276 nucleocytoplasmic proteins 251:276 nucleocytoplasmic proteins 251:276 INTRODUCTION O-GlcNAcylation occurs via an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety linked to the side chain hydroxyl of a serine or threonine residue on nucleocytoplasmic proteins. 27131860 12 61 from gastritis 1860:1868 arg1 elevated 1795:1802 elevated 1795:1802 elevated 1795:1802 In addition, the expression of O-GlcNAcylation and OGT was more elevated in H. pylori-infected chronic gastritis than in chronic gastritis without H. pylori infection. 27131860 12 61 from gastritis 1860:1868 arg1 expression 1748:1757 the expression 1744:1757 the expression of O-GlcNAcylation and OGT 1744:1784 In addition, the expression of O-GlcNAcylation and OGT was more elevated in H. pylori-infected chronic gastritis than in chronic gastritis without H. pylori infection. 27131860 13 62 theme nuclear 1946:1952 arg1 expression 1954:1963 its nuclear expression 1942:1963 its nuclear expression 1942:1963 CONCLUSIONS O-GlcNAcylation expression and its nuclear expression were associated with the carcinogenesis and progression of GC. 27131860 1 63 theme β-N-acetylglucosamine 141:161 arg1 moiety 174:179 an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety 129:179 an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety linked to the side chain hydroxyl of a serine or threonine residue on nucleocytoplasmic proteins 129:276 INTRODUCTION O-GlcNAcylation occurs via an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety linked to the side chain hydroxyl of a serine or threonine residue on nucleocytoplasmic proteins. 27131860 5 64 gly O-GlcNAcylation 874:888 arg1 rim 940:942 the nuclear rim 928:942 the nuclear rim 928:942 RESULTS O-GlcNAcylation was expressed in the nucleus and both the nuclear rim and cytoplasm. 27131860 5 64 gly O-GlcNAcylation 874:888 arg1 nucleus 911:917 the nucleus 907:917 the nucleus 907:917 RESULTS O-GlcNAcylation was expressed in the nucleus and both the nuclear rim and cytoplasm. 27131860 0 65 theme gastric 70:76 arg1 carcinoma 78:86 gastric carcinoma 70:86 gastric carcinoma 70:86 O-GlcNAcylation is associated with the development and progression of gastric carcinoma. 27131860 9 66 theme higher 1275:1280 arg1 stage 1285:1289 higher pT stage 1275:1289 higher pT stage 1275:1289 O-GlcNAcylation expression was higher in GC with intestinal type, higher pT stage and nodal metastasis, while OGT expression was higher in GC with nodal metastasis. 27131860 1 67 theme O-GlcNAc 164:171 arg1 moiety 174:179 an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety 129:179 an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety linked to the side chain hydroxyl of a serine or threonine residue on nucleocytoplasmic proteins 129:276 INTRODUCTION O-GlcNAcylation occurs via an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety linked to the side chain hydroxyl of a serine or threonine residue on nucleocytoplasmic proteins. 27131860 13 68 theme O-GlcNAcylation 1911:1925 arg1 expression 1927:1936 CONCLUSIONS O-GlcNAcylation expression 1899:1936 CONCLUSIONS O-GlcNAcylation expression 1899:1936 CONCLUSIONS O-GlcNAcylation expression and its nuclear expression were associated with the carcinogenesis and progression of GC. 27131860 9 69 theme nodal 1295:1299 arg1 metastasis 1301:1310 nodal metastasis 1295:1310 nodal metastasis 1295:1310 O-GlcNAcylation expression was higher in GC with intestinal type, higher pT stage and nodal metastasis, while OGT expression was higher in GC with nodal metastasis. 27131860 2 70 theme cancers 378:384 arg1 cancers 378:384 human cancers 372:384 human cancers 372:384 This reaction, which is catalyzed by O-GlcNAc-transferase (OGT), is involved in a variety of human cancers; however, its clinical significance in gastric carcinomas (GC) has been poorly investigated in vivo. 27131860 2 70 theme cancers 378:384 arg1 variety 361:367 a variety 359:367 a variety of human cancers 359:384 This reaction, which is catalyzed by O-GlcNAc-transferase (OGT), is involved in a variety of human cancers; however, its clinical significance in gastric carcinomas (GC) has been poorly investigated in vivo. 27131860 9 71 theme OGT 1319:1321 arg1 expression 1323:1332 OGT expression 1319:1332 OGT expression 1319:1332 O-GlcNAcylation expression was higher in GC with intestinal type, higher pT stage and nodal metastasis, while OGT expression was higher in GC with nodal metastasis. 27131860 1 72 theme INTRODUCTION 89:100 arg1 O-GlcNAcylation 102:116 INTRODUCTION O-GlcNAcylation 89:116 INTRODUCTION O-GlcNAcylation 89:116 INTRODUCTION O-GlcNAcylation occurs via an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety linked to the side chain hydroxyl of a serine or threonine residue on nucleocytoplasmic proteins. 27131860 2 73 theme gastric 425:431 arg1 GC 445:446 GC 445:446 GC 445:446 This reaction, which is catalyzed by O-GlcNAc-transferase (OGT), is involved in a variety of human cancers; however, its clinical significance in gastric carcinomas (GC) has been poorly investigated in vivo. 27131860 2 73 theme gastric 425:431 arg1 carcinomas 433:442 gastric carcinomas 425:442 gastric carcinomas (GC) 425:447 This reaction, which is catalyzed by O-GlcNAc-transferase (OGT), is involved in a variety of human cancers; however, its clinical significance in gastric carcinomas (GC) has been poorly investigated in vivo. 27131860 11 74 theme clinical 1715:1722 arg1 stage 1724:1728 higher clinical stage 1708:1728 higher clinical stage 1708:1728 Nuclear O-GlcNAcylation expression in GC was closely associated with large size, moderate and poor differentiation, higher pT stage, nodal metastasis and higher clinical stage. 27131860 10 75 theme nonneoplastic 1481:1493 arg1 tissues 1495:1501 nonneoplastic tissues 1481:1501 nonneoplastic tissues including intestinal metaplasia and normal tissue 1481:1551 Nuclear O-GlcNAcylation expression was more frequently observed in tumors including GC and adenoma than in nonneoplastic tissues including intestinal metaplasia and normal tissue. 27131860 10 75 theme nonneoplastic 1481:1493 arg1 metaplasia 1524:1533 intestinal metaplasia 1513:1533 intestinal metaplasia 1513:1533 Nuclear O-GlcNAcylation expression was more frequently observed in tumors including GC and adenoma than in nonneoplastic tissues including intestinal metaplasia and normal tissue. 27131860 10 75 theme nonneoplastic 1481:1493 arg1 tissue 1546:1551 normal tissue 1539:1551 normal tissue 1539:1551 Nuclear O-GlcNAcylation expression was more frequently observed in tumors including GC and adenoma than in nonneoplastic tissues including intestinal metaplasia and normal tissue. 27131860 11 76 theme large 1623:1627 arg1 size 1629:1632 large size 1623:1632 large size 1623:1632 Nuclear O-GlcNAcylation expression in GC was closely associated with large size, moderate and poor differentiation, higher pT stage, nodal metastasis and higher clinical stage. 27131860 0 77 dep development 39:49 arg1 the 35:37 the 35:37 the 35:37 O-GlcNAcylation is associated with the development and progression of gastric carcinoma. 27131860 12 78 theme chronic 1826:1832 arg1 gastritis 1834:1842 H. pylori-infected chronic gastritis 1807:1842 H. pylori-infected chronic gastritis 1807:1842 In addition, the expression of O-GlcNAcylation and OGT was more elevated in H. pylori-infected chronic gastritis than in chronic gastritis without H. pylori infection. 27131860 10 79 theme normal 1539:1544 arg1 tissue 1546:1551 normal tissue 1539:1551 normal tissue 1539:1551 Nuclear O-GlcNAcylation expression was more frequently observed in tumors including GC and adenoma than in nonneoplastic tissues including intestinal metaplasia and normal tissue. 27131860 4 80 theme gastritis 800:808 arg1 tissues 781:787 20 tissues 778:787 20 tissues of chronic gastritis 778:808 Their expressions were also studied in 20 tissues of chronic gastritis according to Helicobacter pylori (H. pylori) infection. 27131860 12 81 theme H. 1878:1879 arg1 infection 1888:1896 H. pylori infection 1878:1896 H. pylori infection 1878:1896 In addition, the expression of O-GlcNAcylation and OGT was more elevated in H. pylori-infected chronic gastritis than in chronic gastritis without H. pylori infection. 27131860 12 82 from gastritis 1834:1842 arg1 elevated 1795:1802 elevated 1795:1802 elevated 1795:1802 In addition, the expression of O-GlcNAcylation and OGT was more elevated in H. pylori-infected chronic gastritis than in chronic gastritis without H. pylori infection. 27131860 12 82 from gastritis 1834:1842 arg1 expression 1748:1757 the expression 1744:1757 the expression of O-GlcNAcylation and OGT 1744:1784 In addition, the expression of O-GlcNAcylation and OGT was more elevated in H. pylori-infected chronic gastritis than in chronic gastritis without H. pylori infection. 27131860 1 83 link O-linked 132:139 arg1 moiety 174:179 an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety 129:179 an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety linked to the side chain hydroxyl of a serine or threonine residue on nucleocytoplasmic proteins 129:276 INTRODUCTION O-GlcNAcylation occurs via an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety linked to the side chain hydroxyl of a serine or threonine residue on nucleocytoplasmic proteins. 27131860 3 84 theme adjacent 645:652 arg1 tissues 730:736 24 normal gastric tissues 712:736 24 normal gastric tissues 712:736 MATERIALS AND METHODS Immunohistochemical staining for O-GlcNAcylation and OGT was performed in 64 primary GCs, 40 gastric adenomas and nonneoplastic tissues adjacent to GCs, including 31 tissues of intestinal metaplasia and 24 normal gastric tissues. 27131860 3 84 theme adjacent 645:652 arg1 tissues 675:681 31 tissues 672:681 31 tissues of intestinal metaplasia 672:706 MATERIALS AND METHODS Immunohistochemical staining for O-GlcNAcylation and OGT was performed in 64 primary GCs, 40 gastric adenomas and nonneoplastic tissues adjacent to GCs, including 31 tissues of intestinal metaplasia and 24 normal gastric tissues. 27131860 3 84 theme adjacent 645:652 arg1 GCs 594:596 64 primary GCs 583:596 64 primary GCs 583:596 MATERIALS AND METHODS Immunohistochemical staining for O-GlcNAcylation and OGT was performed in 64 primary GCs, 40 gastric adenomas and nonneoplastic tissues adjacent to GCs, including 31 tissues of intestinal metaplasia and 24 normal gastric tissues. 27131860 1 85 theme threonine 230:238 arg1 residue 240:246 a serine or threonine residue 218:246 residue 240:246 INTRODUCTION O-GlcNAcylation occurs via an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety linked to the side chain hydroxyl of a serine or threonine residue on nucleocytoplasmic proteins. 27131860 11 86 theme higher 1670:1675 arg1 stage 1680:1684 higher pT stage 1670:1684 higher pT stage 1670:1684 Nuclear O-GlcNAcylation expression in GC was closely associated with large size, moderate and poor differentiation, higher pT stage, nodal metastasis and higher clinical stage. 26531776 6 0 theme subunit 994:1000 arg1 20S 1002:1004 proteasome subunit 20S 983:1004 proteasome subunit 20S 983:1004 Upregulation of proteins, including ubiquitin-activating enzyme E1, proteasome subunit 20S, cullin-associated NEDD8-dissociated protein 1, ezrin, and downregulation of the protein nucleoside diphosphate kinase B, were confirmed by western blot analysis. 26531776 4 1 theme O-GlcNAcase 617:627 arg1 PUGNAc 710:715 the O-GlcNAcase inhibitor, O-(2-acetamido-2-deoxy-d-glucopyranosylidene)amino-N-phenylcarbamate (PUGNAc) 613:716 PUGNAc 710:715 Here, using adenosine 5'-triphosphate affinity chromatography, we employed a proteomic approach in order to identify differentially expressed proteins in response to treatment with the O-GlcNAcase inhibitor, O-(2-acetamido-2-deoxy-d-glucopyranosylidene)amino-N-phenylcarbamate (PUGNAc), in mouse C2C12 myotube cells. 26531776 6 2 theme proteasome 983:992 arg1 20S 1002:1004 proteasome subunit 20S 983:1004 proteasome subunit 20S 983:1004 Upregulation of proteins, including ubiquitin-activating enzyme E1, proteasome subunit 20S, cullin-associated NEDD8-dissociated protein 1, ezrin, and downregulation of the protein nucleoside diphosphate kinase B, were confirmed by western blot analysis. 26531776 5 3 contain have 838:841 arg2 activity 867:874 adenosinetriphosphatase activity 843:874 adenosinetriphosphatase activity 843:874 Among 205 selected genes, we identified 68 nucleotide-binding proteins, 14 proteins that have adenosinetriphosphatase activity, and 10 proteins with ligase activity. 26531776 5 3 contain have 838:841 arg1 proteins 824:831 14 proteins 821:831 14 proteins that have adenosinetriphosphatase activity 821:874 Among 205 selected genes, we identified 68 nucleotide-binding proteins, 14 proteins that have adenosinetriphosphatase activity, and 10 proteins with ligase activity. 26531776 1 4 theme cell 177:180 arg1 signaling 182:190 cell signaling 177:190 cell signaling 177:190 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) regulates many cellular processes including the cell cycle, cell signaling, and protein trafficking. 26531776 3 5 theme cellular 368:375 arg1 proteins 377:384 cellular proteins 368:384 cellular proteins that are induced by elevated O-GlcNAcylation 368:429 Therefore, it is necessary to identify cellular proteins that are induced by elevated O-GlcNAcylation. 26531776 2 6 theme type 312:315 arg1 diabetes 319:326 type 2 diabetes 312:326 type 2 diabetes 312:326 Dysregulation of O-GlcNAcylation may be involved in the development of insulin resistance and type 2 diabetes. 26531776 7 7 theme PUGNAc 1263:1268 arg1 treatment 1270:1278 PUGNAc treatment 1263:1278 PUGNAc treatment 1263:1278 In particular, we found that the protein ubiquitination level in C2C12 cells was increased by PUGNAc treatment. 26531776 4 8 with treatment 598:606 arg1 PUGNAc 710:715 the O-GlcNAcase inhibitor, O-(2-acetamido-2-deoxy-d-glucopyranosylidene)amino-N-phenylcarbamate (PUGNAc) 613:716 PUGNAc 710:715 Here, using adenosine 5'-triphosphate affinity chromatography, we employed a proteomic approach in order to identify differentially expressed proteins in response to treatment with the O-GlcNAcase inhibitor, O-(2-acetamido-2-deoxy-d-glucopyranosylidene)amino-N-phenylcarbamate (PUGNAc), in mouse C2C12 myotube cells. 26531776 1 9 theme O-linked 62:69 arg1 β-N-acetylglucosaminylation 71:97 O-linked β-N-acetylglucosaminylation 62:97 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) 62:115 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) regulates many cellular processes including the cell cycle, cell signaling, and protein trafficking. 26531776 1 9 theme O-linked 62:69 arg1 O-GlcNAcylation 100:114 O-GlcNAcylation 100:114 O-GlcNAcylation 100:114 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) regulates many cellular processes including the cell cycle, cell signaling, and protein trafficking. 26531776 4 10 theme inhibitor 629:637 arg1 PUGNAc 710:715 the O-GlcNAcase inhibitor, O-(2-acetamido-2-deoxy-d-glucopyranosylidene)amino-N-phenylcarbamate (PUGNAc) 613:716 PUGNAc 710:715 Here, using adenosine 5'-triphosphate affinity chromatography, we employed a proteomic approach in order to identify differentially expressed proteins in response to treatment with the O-GlcNAcase inhibitor, O-(2-acetamido-2-deoxy-d-glucopyranosylidene)amino-N-phenylcarbamate (PUGNAc), in mouse C2C12 myotube cells. 26531776 4 11 dep treatment 598:606 arg1 response 586:593 response 586:593 response 586:593 Here, using adenosine 5'-triphosphate affinity chromatography, we employed a proteomic approach in order to identify differentially expressed proteins in response to treatment with the O-GlcNAcase inhibitor, O-(2-acetamido-2-deoxy-d-glucopyranosylidene)amino-N-phenylcarbamate (PUGNAc), in mouse C2C12 myotube cells. 26531776 8 12 theme proteomic 1322:1330 arg1 profiles 1332:1339 quantitative proteomic profiles 1309:1339 quantitative proteomic profiles of myotube cells 1309:1356 This is the first report of quantitative proteomic profiles of myotube cells after treatment with PUGNAc, and our results demonstrate the potential to enhance understanding of the relationship between insulin resistance, O-GlcNAc, and PUGNAc in the future. 26531776 5 13 theme ligase 898:903 arg1 activity 905:912 ligase activity 898:912 ligase activity 898:912 Among 205 selected genes, we identified 68 nucleotide-binding proteins, 14 proteins that have adenosinetriphosphatase activity, and 10 proteins with ligase activity. 26531776 2 14 theme resistance 297:306 arg1 development 274:284 the development 270:284 the development of insulin resistance and type 2 diabetes 270:326 Dysregulation of O-GlcNAcylation may be involved in the development of insulin resistance and type 2 diabetes. 26531776 6 15 theme western 1146:1152 arg1 analysis 1159:1166 western blot analysis 1146:1166 western blot analysis 1146:1166 Upregulation of proteins, including ubiquitin-activating enzyme E1, proteasome subunit 20S, cullin-associated NEDD8-dissociated protein 1, ezrin, and downregulation of the protein nucleoside diphosphate kinase B, were confirmed by western blot analysis. 26531776 1 16 link O-linked 62:69 arg1 β-N-acetylglucosaminylation 71:97 O-linked β-N-acetylglucosaminylation 62:97 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) 62:115 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) regulates many cellular processes including the cell cycle, cell signaling, and protein trafficking. 26531776 1 16 link O-linked 62:69 arg1 O-GlcNAcylation 100:114 O-GlcNAcylation 100:114 O-GlcNAcylation 100:114 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) regulates many cellular processes including the cell cycle, cell signaling, and protein trafficking. 26531776 6 17 theme ubiquitin-activating 951:970 arg1 E1 979:980 ubiquitin-activating enzyme E1 951:980 ubiquitin-activating enzyme E1 951:980 Upregulation of proteins, including ubiquitin-activating enzyme E1, proteasome subunit 20S, cullin-associated NEDD8-dissociated protein 1, ezrin, and downregulation of the protein nucleoside diphosphate kinase B, were confirmed by western blot analysis. 26531776 2 18 theme insulin 289:295 arg1 resistance 297:306 insulin resistance 289:306 insulin resistance 289:306 Dysregulation of O-GlcNAcylation may be involved in the development of insulin resistance and type 2 diabetes. 26531776 8 19 theme myotube 1344:1350 arg1 cells 1352:1356 myotube cells 1344:1356 myotube cells 1344:1356 This is the first report of quantitative proteomic profiles of myotube cells after treatment with PUGNAc, and our results demonstrate the potential to enhance understanding of the relationship between insulin resistance, O-GlcNAc, and PUGNAc in the future. 26531776 6 20 theme blot 1154:1157 arg1 analysis 1159:1166 western blot analysis 1146:1166 western blot analysis 1146:1166 Upregulation of proteins, including ubiquitin-activating enzyme E1, proteasome subunit 20S, cullin-associated NEDD8-dissociated protein 1, ezrin, and downregulation of the protein nucleoside diphosphate kinase B, were confirmed by western blot analysis. 26531776 4 21 theme proteomic 509:517 arg1 approach 519:526 a proteomic approach 507:526 a proteomic approach in order to identify differentially expressed proteins in response to treatment with the O-GlcNAcase inhibitor, O-(2-acetamido-2-deoxy-d-glucopyranosylidene)amino-N-phenylcarbamate (PUGNAc), in mouse C2C12 myotube cells 507:746 Here, using adenosine 5'-triphosphate affinity chromatography, we employed a proteomic approach in order to identify differentially expressed proteins in response to treatment with the O-GlcNAcase inhibitor, O-(2-acetamido-2-deoxy-d-glucopyranosylidene)amino-N-phenylcarbamate (PUGNAc), in mouse C2C12 myotube cells. 26531776 8 22 theme quantitative 1309:1320 arg1 profiles 1332:1339 quantitative proteomic profiles 1309:1339 quantitative proteomic profiles of myotube cells 1309:1356 This is the first report of quantitative proteomic profiles of myotube cells after treatment with PUGNAc, and our results demonstrate the potential to enhance understanding of the relationship between insulin resistance, O-GlcNAc, and PUGNAc in the future. 26531776 6 23 theme enzyme 972:977 arg1 E1 979:980 ubiquitin-activating enzyme E1 951:980 ubiquitin-activating enzyme E1 951:980 Upregulation of proteins, including ubiquitin-activating enzyme E1, proteasome subunit 20S, cullin-associated NEDD8-dissociated protein 1, ezrin, and downregulation of the protein nucleoside diphosphate kinase B, were confirmed by western blot analysis. 26531776 4 24 theme C2C12 728:732 arg1 cells 742:746 mouse C2C12 myotube cells 722:746 mouse C2C12 myotube cells 722:746 Here, using adenosine 5'-triphosphate affinity chromatography, we employed a proteomic approach in order to identify differentially expressed proteins in response to treatment with the O-GlcNAcase inhibitor, O-(2-acetamido-2-deoxy-d-glucopyranosylidene)amino-N-phenylcarbamate (PUGNAc), in mouse C2C12 myotube cells. 26531776 7 25 from level 1225:1229 arg1 cells 1240:1244 C2C12 cells 1234:1244 C2C12 cells 1234:1244 In particular, we found that the protein ubiquitination level in C2C12 cells was increased by PUGNAc treatment. 26531776 5 26 with proteins 884:891 arg1 activity 905:912 ligase activity 898:912 ligase activity 898:912 Among 205 selected genes, we identified 68 nucleotide-binding proteins, 14 proteins that have adenosinetriphosphatase activity, and 10 proteins with ligase activity. 26531776 8 27 theme profiles 1332:1339 arg1 report 1299:1304 the first report 1289:1304 the first report of quantitative proteomic profiles of myotube cells 1289:1356 This is the first report of quantitative proteomic profiles of myotube cells after treatment with PUGNAc, and our results demonstrate the potential to enhance understanding of the relationship between insulin resistance, O-GlcNAc, and PUGNAc in the future. 26531776 8 27 theme profiles 1332:1339 arg1 This 1281:1284 This 1281:1284 This 1281:1284 This is the first report of quantitative proteomic profiles of myotube cells after treatment with PUGNAc, and our results demonstrate the potential to enhance understanding of the relationship between insulin resistance, O-GlcNAc, and PUGNAc in the future. 26531776 4 28 theme mouse 722:726 arg1 cells 742:746 mouse C2C12 myotube cells 722:746 mouse C2C12 myotube cells 722:746 Here, using adenosine 5'-triphosphate affinity chromatography, we employed a proteomic approach in order to identify differentially expressed proteins in response to treatment with the O-GlcNAcase inhibitor, O-(2-acetamido-2-deoxy-d-glucopyranosylidene)amino-N-phenylcarbamate (PUGNAc), in mouse C2C12 myotube cells. 26531776 7 29 theme C2C12 1234:1238 arg1 cells 1240:1244 C2C12 cells 1234:1244 C2C12 cells 1234:1244 In particular, we found that the protein ubiquitination level in C2C12 cells was increased by PUGNAc treatment. 26531776 8 30 theme insulin 1482:1488 arg1 resistance 1490:1499 insulin resistance 1482:1499 insulin resistance 1482:1499 This is the first report of quantitative proteomic profiles of myotube cells after treatment with PUGNAc, and our results demonstrate the potential to enhance understanding of the relationship between insulin resistance, O-GlcNAc, and PUGNAc in the future. 26531776 2 31 theme diabetes 319:326 arg1 development 274:284 the development 270:284 the development of insulin resistance and type 2 diabetes 270:326 Dysregulation of O-GlcNAcylation may be involved in the development of insulin resistance and type 2 diabetes. 26531776 0 32 theme protein 15:21 arg1 ubiquitination 23:36 protein ubiquitination 15:36 protein ubiquitination 15:36 PUGNAc induces protein ubiquitination in C2C12 myotube cells. 26531776 5 33 theme selected 759:766 arg1 genes 768:772 205 selected genes 755:772 205 selected genes 755:772 Among 205 selected genes, we identified 68 nucleotide-binding proteins, 14 proteins that have adenosinetriphosphatase activity, and 10 proteins with ligase activity. 26531776 1 34 theme many 127:130 arg1 cycle 170:174 the cell cycle 161:174 the cell cycle 161:174 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) regulates many cellular processes including the cell cycle, cell signaling, and protein trafficking. 26531776 1 34 theme many 127:130 arg1 signaling 182:190 cell signaling 177:190 cell signaling 177:190 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) regulates many cellular processes including the cell cycle, cell signaling, and protein trafficking. 26531776 1 34 theme many 127:130 arg1 processes 141:149 many cellular processes 127:149 many cellular processes including the cell cycle, cell signaling, and protein trafficking 127:215 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) regulates many cellular processes including the cell cycle, cell signaling, and protein trafficking. 26531776 1 34 theme many 127:130 arg1 trafficking 205:215 protein trafficking 197:215 protein trafficking 197:215 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) regulates many cellular processes including the cell cycle, cell signaling, and protein trafficking. 26531776 4 35 theme amino-N-phenylcarbamate 685:707 arg1 PUGNAc 710:715 the O-GlcNAcase inhibitor, O-(2-acetamido-2-deoxy-d-glucopyranosylidene)amino-N-phenylcarbamate (PUGNAc) 613:716 PUGNAc 710:715 Here, using adenosine 5'-triphosphate affinity chromatography, we employed a proteomic approach in order to identify differentially expressed proteins in response to treatment with the O-GlcNAcase inhibitor, O-(2-acetamido-2-deoxy-d-glucopyranosylidene)amino-N-phenylcarbamate (PUGNAc), in mouse C2C12 myotube cells. 26531776 0 36 theme C2C12 41:45 arg1 cells 55:59 C2C12 myotube cells 41:59 C2C12 myotube cells 41:59 PUGNAc induces protein ubiquitination in C2C12 myotube cells. 26531776 4 37 theme affinity 470:477 arg1 chromatography 479:492 adenosine 5'-triphosphate affinity chromatography 444:492 adenosine 5'-triphosphate affinity chromatography 444:492 Here, using adenosine 5'-triphosphate affinity chromatography, we employed a proteomic approach in order to identify differentially expressed proteins in response to treatment with the O-GlcNAcase inhibitor, O-(2-acetamido-2-deoxy-d-glucopyranosylidene)amino-N-phenylcarbamate (PUGNAc), in mouse C2C12 myotube cells. 26531776 1 38 theme protein 197:203 arg1 trafficking 205:215 protein trafficking 197:215 protein trafficking 197:215 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) regulates many cellular processes including the cell cycle, cell signaling, and protein trafficking. 26531776 7 39 theme protein 1202:1208 arg1 level 1225:1229 the protein ubiquitination level 1198:1229 the protein ubiquitination level in C2C12 cells 1198:1244 In particular, we found that the protein ubiquitination level in C2C12 cells was increased by PUGNAc treatment. 26531776 4 40 theme expressed 564:572 arg1 proteins 574:581 differentially expressed proteins 549:581 differentially expressed proteins 549:581 Here, using adenosine 5'-triphosphate affinity chromatography, we employed a proteomic approach in order to identify differentially expressed proteins in response to treatment with the O-GlcNAcase inhibitor, O-(2-acetamido-2-deoxy-d-glucopyranosylidene)amino-N-phenylcarbamate (PUGNAc), in mouse C2C12 myotube cells. 26531776 8 41 theme cells 1352:1356 arg1 profiles 1332:1339 quantitative proteomic profiles 1309:1339 quantitative proteomic profiles of myotube cells 1309:1356 This is the first report of quantitative proteomic profiles of myotube cells after treatment with PUGNAc, and our results demonstrate the potential to enhance understanding of the relationship between insulin resistance, O-GlcNAc, and PUGNAc in the future. 26531776 4 42 dep PUGNAc 710:715 arg1 O- 640:641 the O-GlcNAcase inhibitor, O-(2-acetamido-2-deoxy-d-glucopyranosylidene)amino-N-phenylcarbamate (PUGNAc) 613:716 O- 640:641 Here, using adenosine 5'-triphosphate affinity chromatography, we employed a proteomic approach in order to identify differentially expressed proteins in response to treatment with the O-GlcNAcase inhibitor, O-(2-acetamido-2-deoxy-d-glucopyranosylidene)amino-N-phenylcarbamate (PUGNAc), in mouse C2C12 myotube cells. 26531776 5 43 theme nucleotide-binding 792:809 arg1 proteins 811:818 68 nucleotide-binding proteins 789:818 68 nucleotide-binding proteins 789:818 Among 205 selected genes, we identified 68 nucleotide-binding proteins, 14 proteins that have adenosinetriphosphatase activity, and 10 proteins with ligase activity. 26531776 3 44 theme elevated 406:413 arg1 O-GlcNAcylation 415:429 elevated O-GlcNAcylation 406:429 elevated O-GlcNAcylation 406:429 Therefore, it is necessary to identify cellular proteins that are induced by elevated O-GlcNAcylation. 26531776 6 45 theme NEDD8-dissociated 1025:1041 arg1 protein 1043:1049 cullin-associated NEDD8-dissociated protein 1 1007:1051 cullin-associated NEDD8-dissociated protein 1 1007:1051 Upregulation of proteins, including ubiquitin-activating enzyme E1, proteasome subunit 20S, cullin-associated NEDD8-dissociated protein 1, ezrin, and downregulation of the protein nucleoside diphosphate kinase B, were confirmed by western blot analysis. 26531776 6 46 theme B 1125:1125 arg1 protein 1043:1049 cullin-associated NEDD8-dissociated protein 1 1007:1051 cullin-associated NEDD8-dissociated protein 1 1007:1051 Upregulation of proteins, including ubiquitin-activating enzyme E1, proteasome subunit 20S, cullin-associated NEDD8-dissociated protein 1, ezrin, and downregulation of the protein nucleoside diphosphate kinase B, were confirmed by western blot analysis. 26531776 6 46 theme B 1125:1125 arg1 ezrin 1054:1058 ezrin 1054:1058 ezrin 1054:1058 Upregulation of proteins, including ubiquitin-activating enzyme E1, proteasome subunit 20S, cullin-associated NEDD8-dissociated protein 1, ezrin, and downregulation of the protein nucleoside diphosphate kinase B, were confirmed by western blot analysis. 26531776 6 46 theme B 1125:1125 arg1 downregulation 1065:1078 downregulation 1065:1078 downregulation of the protein nucleoside diphosphate kinase B 1065:1125 Upregulation of proteins, including ubiquitin-activating enzyme E1, proteasome subunit 20S, cullin-associated NEDD8-dissociated protein 1, ezrin, and downregulation of the protein nucleoside diphosphate kinase B, were confirmed by western blot analysis. 26531776 6 46 theme B 1125:1125 arg1 Upregulation 915:926 Upregulation 915:926 Upregulation of proteins, including ubiquitin-activating enzyme E1 915:980 Upregulation of proteins, including ubiquitin-activating enzyme E1, proteasome subunit 20S, cullin-associated NEDD8-dissociated protein 1, ezrin, and downregulation of the protein nucleoside diphosphate kinase B, were confirmed by western blot analysis. 26531776 6 46 theme B 1125:1125 arg1 20S 1002:1004 proteasome subunit 20S 983:1004 proteasome subunit 20S 983:1004 Upregulation of proteins, including ubiquitin-activating enzyme E1, proteasome subunit 20S, cullin-associated NEDD8-dissociated protein 1, ezrin, and downregulation of the protein nucleoside diphosphate kinase B, were confirmed by western blot analysis. 26531776 1 47 theme cellular 132:139 arg1 cycle 170:174 the cell cycle 161:174 the cell cycle 161:174 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) regulates many cellular processes including the cell cycle, cell signaling, and protein trafficking. 26531776 1 47 theme cellular 132:139 arg1 signaling 182:190 cell signaling 177:190 cell signaling 177:190 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) regulates many cellular processes including the cell cycle, cell signaling, and protein trafficking. 26531776 1 47 theme cellular 132:139 arg1 processes 141:149 many cellular processes 127:149 many cellular processes including the cell cycle, cell signaling, and protein trafficking 127:215 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) regulates many cellular processes including the cell cycle, cell signaling, and protein trafficking. 26531776 1 47 theme cellular 132:139 arg1 trafficking 205:215 protein trafficking 197:215 protein trafficking 197:215 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) regulates many cellular processes including the cell cycle, cell signaling, and protein trafficking. 26531776 0 48 theme myotube 47:53 arg1 cells 55:59 C2C12 myotube cells 41:59 C2C12 myotube cells 41:59 PUGNAc induces protein ubiquitination in C2C12 myotube cells. 26531776 6 49 theme cullin-associated 1007:1023 arg1 protein 1043:1049 cullin-associated NEDD8-dissociated protein 1 1007:1051 cullin-associated NEDD8-dissociated protein 1 1007:1051 Upregulation of proteins, including ubiquitin-activating enzyme E1, proteasome subunit 20S, cullin-associated NEDD8-dissociated protein 1, ezrin, and downregulation of the protein nucleoside diphosphate kinase B, were confirmed by western blot analysis. 26531776 2 50 theme O-GlcNAcylation 235:249 arg1 Dysregulation 218:230 Dysregulation 218:230 Dysregulation of O-GlcNAcylation 218:249 Dysregulation of O-GlcNAcylation may be involved in the development of insulin resistance and type 2 diabetes. 26531776 8 51 with treatment 1364:1372 arg1 PUGNAc 1379:1384 PUGNAc 1379:1384 PUGNAc 1379:1384 This is the first report of quantitative proteomic profiles of myotube cells after treatment with PUGNAc, and our results demonstrate the potential to enhance understanding of the relationship between insulin resistance, O-GlcNAc, and PUGNAc in the future. 26531776 7 52 theme ubiquitination 1210:1223 arg1 level 1225:1229 the protein ubiquitination level 1198:1229 the protein ubiquitination level in C2C12 cells 1198:1244 In particular, we found that the protein ubiquitination level in C2C12 cells was increased by PUGNAc treatment. 26531776 8 53 theme relationship 1461:1472 arg1 understanding 1440:1452 understanding 1440:1452 understanding of the relationship between insulin resistance, O-GlcNAc, and PUGNAc 1440:1521 This is the first report of quantitative proteomic profiles of myotube cells after treatment with PUGNAc, and our results demonstrate the potential to enhance understanding of the relationship between insulin resistance, O-GlcNAc, and PUGNAc in the future. 26531776 6 54 theme kinase 1118:1123 arg1 B 1125:1125 the protein nucleoside diphosphate kinase B 1083:1125 the protein nucleoside diphosphate kinase B 1083:1125 Upregulation of proteins, including ubiquitin-activating enzyme E1, proteasome subunit 20S, cullin-associated NEDD8-dissociated protein 1, ezrin, and downregulation of the protein nucleoside diphosphate kinase B, were confirmed by western blot analysis. 26531776 4 55 theme 5'-triphosphate 454:468 arg1 chromatography 479:492 adenosine 5'-triphosphate affinity chromatography 444:492 adenosine 5'-triphosphate affinity chromatography 444:492 Here, using adenosine 5'-triphosphate affinity chromatography, we employed a proteomic approach in order to identify differentially expressed proteins in response to treatment with the O-GlcNAcase inhibitor, O-(2-acetamido-2-deoxy-d-glucopyranosylidene)amino-N-phenylcarbamate (PUGNAc), in mouse C2C12 myotube cells. 26531776 5 56 with proteins 824:831 arg1 activity 905:912 ligase activity 898:912 ligase activity 898:912 Among 205 selected genes, we identified 68 nucleotide-binding proteins, 14 proteins that have adenosinetriphosphatase activity, and 10 proteins with ligase activity. 26531776 8 57 theme first 1293:1297 arg1 report 1299:1304 the first report 1289:1304 the first report of quantitative proteomic profiles of myotube cells 1289:1356 This is the first report of quantitative proteomic profiles of myotube cells after treatment with PUGNAc, and our results demonstrate the potential to enhance understanding of the relationship between insulin resistance, O-GlcNAc, and PUGNAc in the future. 26531776 8 57 theme first 1293:1297 arg1 This 1281:1284 This 1281:1284 This 1281:1284 This is the first report of quantitative proteomic profiles of myotube cells after treatment with PUGNAc, and our results demonstrate the potential to enhance understanding of the relationship between insulin resistance, O-GlcNAc, and PUGNAc in the future. 26531776 6 58 theme diphosphate 1106:1116 arg1 kinase 1118:1123 the protein nucleoside diphosphate kinase 1083:1123 the protein nucleoside diphosphate kinase B 1083:1125 Upregulation of proteins, including ubiquitin-activating enzyme E1, proteasome subunit 20S, cullin-associated NEDD8-dissociated protein 1, ezrin, and downregulation of the protein nucleoside diphosphate kinase B, were confirmed by western blot analysis. 26531776 6 59 theme proteins 931:938 arg1 protein 1043:1049 cullin-associated NEDD8-dissociated protein 1 1007:1051 cullin-associated NEDD8-dissociated protein 1 1007:1051 Upregulation of proteins, including ubiquitin-activating enzyme E1, proteasome subunit 20S, cullin-associated NEDD8-dissociated protein 1, ezrin, and downregulation of the protein nucleoside diphosphate kinase B, were confirmed by western blot analysis. 26531776 6 59 theme proteins 931:938 arg1 ezrin 1054:1058 ezrin 1054:1058 ezrin 1054:1058 Upregulation of proteins, including ubiquitin-activating enzyme E1, proteasome subunit 20S, cullin-associated NEDD8-dissociated protein 1, ezrin, and downregulation of the protein nucleoside diphosphate kinase B, were confirmed by western blot analysis. 26531776 6 59 theme proteins 931:938 arg1 downregulation 1065:1078 downregulation 1065:1078 downregulation of the protein nucleoside diphosphate kinase B 1065:1125 Upregulation of proteins, including ubiquitin-activating enzyme E1, proteasome subunit 20S, cullin-associated NEDD8-dissociated protein 1, ezrin, and downregulation of the protein nucleoside diphosphate kinase B, were confirmed by western blot analysis. 26531776 6 59 theme proteins 931:938 arg1 Upregulation 915:926 Upregulation 915:926 Upregulation of proteins, including ubiquitin-activating enzyme E1 915:980 Upregulation of proteins, including ubiquitin-activating enzyme E1, proteasome subunit 20S, cullin-associated NEDD8-dissociated protein 1, ezrin, and downregulation of the protein nucleoside diphosphate kinase B, were confirmed by western blot analysis. 26531776 6 59 theme proteins 931:938 arg1 20S 1002:1004 proteasome subunit 20S 983:1004 proteasome subunit 20S 983:1004 Upregulation of proteins, including ubiquitin-activating enzyme E1, proteasome subunit 20S, cullin-associated NEDD8-dissociated protein 1, ezrin, and downregulation of the protein nucleoside diphosphate kinase B, were confirmed by western blot analysis. 26531776 4 60 theme adenosine 444:452 arg1 chromatography 479:492 adenosine 5'-triphosphate affinity chromatography 444:492 adenosine 5'-triphosphate affinity chromatography 444:492 Here, using adenosine 5'-triphosphate affinity chromatography, we employed a proteomic approach in order to identify differentially expressed proteins in response to treatment with the O-GlcNAcase inhibitor, O-(2-acetamido-2-deoxy-d-glucopyranosylidene)amino-N-phenylcarbamate (PUGNAc), in mouse C2C12 myotube cells. 26531776 5 61 with proteins 811:818 arg1 activity 905:912 ligase activity 898:912 ligase activity 898:912 Among 205 selected genes, we identified 68 nucleotide-binding proteins, 14 proteins that have adenosinetriphosphatase activity, and 10 proteins with ligase activity. 26531776 1 62 theme cell 165:168 arg1 cycle 170:174 the cell cycle 161:174 the cell cycle 161:174 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) regulates many cellular processes including the cell cycle, cell signaling, and protein trafficking. 26531776 6 63 theme nucleoside 1095:1104 arg1 kinase 1118:1123 the protein nucleoside diphosphate kinase 1083:1123 the protein nucleoside diphosphate kinase B 1083:1125 Upregulation of proteins, including ubiquitin-activating enzyme E1, proteasome subunit 20S, cullin-associated NEDD8-dissociated protein 1, ezrin, and downregulation of the protein nucleoside diphosphate kinase B, were confirmed by western blot analysis. 26531776 5 64 theme adenosinetriphosphatase 843:865 arg1 activity 867:874 adenosinetriphosphatase activity 843:874 adenosinetriphosphatase activity 843:874 Among 205 selected genes, we identified 68 nucleotide-binding proteins, 14 proteins that have adenosinetriphosphatase activity, and 10 proteins with ligase activity. 26531776 6 65 theme protein 1087:1093 arg1 kinase 1118:1123 the protein nucleoside diphosphate kinase 1083:1123 the protein nucleoside diphosphate kinase B 1083:1125 Upregulation of proteins, including ubiquitin-activating enzyme E1, proteasome subunit 20S, cullin-associated NEDD8-dissociated protein 1, ezrin, and downregulation of the protein nucleoside diphosphate kinase B, were confirmed by western blot analysis. 26531776 4 66 theme myotube 734:740 arg1 cells 742:746 mouse C2C12 myotube cells 722:746 mouse C2C12 myotube cells 722:746 Here, using adenosine 5'-triphosphate affinity chromatography, we employed a proteomic approach in order to identify differentially expressed proteins in response to treatment with the O-GlcNAcase inhibitor, O-(2-acetamido-2-deoxy-d-glucopyranosylidene)amino-N-phenylcarbamate (PUGNAc), in mouse C2C12 myotube cells. 26531776 4 67 theme 2-acetamido-2-deoxy-d-glucopyranosylidene 643:683 arg1 PUGNAc 710:715 the O-GlcNAcase inhibitor, O-(2-acetamido-2-deoxy-d-glucopyranosylidene)amino-N-phenylcarbamate (PUGNAc) 613:716 PUGNAc 710:715 Here, using adenosine 5'-triphosphate affinity chromatography, we employed a proteomic approach in order to identify differentially expressed proteins in response to treatment with the O-GlcNAcase inhibitor, O-(2-acetamido-2-deoxy-d-glucopyranosylidene)amino-N-phenylcarbamate (PUGNAc), in mouse C2C12 myotube cells. 25861849 3 0 gly fucosylation 428:439 arg1 glycans 455:461 N/O-linked glycans 444:461 N/O-linked glycans 444:461 AAL recognizes both α1-3/1-4 and α1-6 fucosylation on N/O-linked glycans. 25861849 6 1 theme ELISA 755:759 arg1 kit 761:763 a lectin-antibody ELISA kit 737:763 a lectin-antibody ELISA kit using PhoSL to determine core-Fuc-Hpt levels in sera from colorectal or pancreatic cancer patients 737:862 METHODS We developed a lectin-antibody ELISA kit using PhoSL to determine core-Fuc-Hpt levels in sera from colorectal or pancreatic cancer patients. 25861849 9 2 theme colorectal 1148:1157 arg1 lines 1171:1175 Hpt-transfected colorectal cancer cell lines 1132:1175 Hpt-transfected colorectal cancer cell lines 1132:1175 Hpt-transfected colorectal cancer cell lines produced significant amounts of core-Fuc-Hpt, suggesting that colorectal cancer tissues produce core-Fuc-Hpt. 25861849 7 3 theme cancer 931:936 arg1 patients 938:945 pancreatic cancer patients 920:945 pancreatic cancer patients 920:945 RESULTS Serum levels of AAL-reactive Hpt are higher in pancreatic cancer patients, whereas those of PhoSL-reactive Hpt are higher in colorectal cancer patients. 25861849 10 4 theme Fuc-Hpt 1320:1326 arg1 patterns 1328:1335 Fuc-Hpt patterns 1320:1335 Fuc-Hpt patterns 1320:1335 CONCLUSIONS These differences in Fuc-Hpt patterns might depend on cancer cells and the surrounding cells, which produce Hpt. 25861849 5 5 theme α1-6 677:680 arg1 core-fucosylation 696:712 core-fucosylation 696:712 core-fucosylation 696:712 Recently, we identified a novel lectin, Pholiota squarrosa lectin (PhoSL), which specifically recognizes α1-6 fucosylation (core-fucosylation). 25861849 5 5 theme α1-6 677:680 arg1 fucosylation 682:693 α1-6 fucosylation 677:693 α1-6 fucosylation (core-fucosylation) 677:713 Recently, we identified a novel lectin, Pholiota squarrosa lectin (PhoSL), which specifically recognizes α1-6 fucosylation (core-fucosylation). 25861849 5 6 theme squarrosa 621:629 arg1 lectin 631:636 Pholiota squarrosa lectin 612:636 Pholiota squarrosa lectin (PhoSL) 612:644 Recently, we identified a novel lectin, Pholiota squarrosa lectin (PhoSL), which specifically recognizes α1-6 fucosylation (core-fucosylation). 25861849 5 6 theme squarrosa 621:629 arg1 lectin 604:609 a novel lectin 596:609 a novel lectin 596:609 Recently, we identified a novel lectin, Pholiota squarrosa lectin (PhoSL), which specifically recognizes α1-6 fucosylation (core-fucosylation). 25861849 5 6 theme squarrosa 621:629 arg1 PhoSL 639:643 PhoSL 639:643 PhoSL 639:643 Recently, we identified a novel lectin, Pholiota squarrosa lectin (PhoSL), which specifically recognizes α1-6 fucosylation (core-fucosylation). 25861849 3 7 from fucosylation 428:439 arg1 glycans 455:461 N/O-linked glycans 444:461 N/O-linked glycans 444:461 AAL recognizes both α1-3/1-4 and α1-6 fucosylation on N/O-linked glycans. 25861849 6 8 theme cancer 848:853 arg1 patients 855:862 colorectal or pancreatic cancer patients 823:862 patients 855:862 METHODS We developed a lectin-antibody ELISA kit using PhoSL to determine core-Fuc-Hpt levels in sera from colorectal or pancreatic cancer patients. 25861849 10 9 theme cancer 1353:1358 arg1 cells 1360:1364 cancer cells 1353:1364 cancer cells 1353:1364 CONCLUSIONS These differences in Fuc-Hpt patterns might depend on cancer cells and the surrounding cells, which produce Hpt. 25861849 4 10 theme biological 499:508 arg1 function 510:517 biological function 499:517 biological function 499:517 These fucosylation types differ in biological function, and in regulation by different fucosyltransferases. 25861849 9 11 theme core-Fuc-Hpt 1209:1220 arg1 core-Fuc-Hpt 1209:1220 core-Fuc-Hpt 1209:1220 core-Fuc-Hpt 1209:1220 Hpt-transfected colorectal cancer cell lines produced significant amounts of core-Fuc-Hpt, suggesting that colorectal cancer tissues produce core-Fuc-Hpt. 25861849 9 11 theme core-Fuc-Hpt 1209:1220 arg1 amounts 1198:1204 significant amounts 1186:1204 significant amounts of core-Fuc-Hpt 1186:1220 Hpt-transfected colorectal cancer cell lines produced significant amounts of core-Fuc-Hpt, suggesting that colorectal cancer tissues produce core-Fuc-Hpt. 25861849 6 12 theme pancreatic 837:846 arg1 patients 855:862 colorectal or pancreatic cancer patients 823:862 patients 855:862 METHODS We developed a lectin-antibody ELISA kit using PhoSL to determine core-Fuc-Hpt levels in sera from colorectal or pancreatic cancer patients. 25861849 0 13 gly core-fucosylated 67:82 arg1 haptoglobin 84:94 core-fucosylated haptoglobin 67:94 core-fucosylated haptoglobin 67:94 Establishment of a novel lectin-antibody ELISA system to determine core-fucosylated haptoglobin. 25861849 6 14 theme lectin-antibody 739:753 arg1 kit 761:763 a lectin-antibody ELISA kit 737:763 a lectin-antibody ELISA kit using PhoSL to determine core-Fuc-Hpt levels in sera from colorectal or pancreatic cancer patients 737:862 METHODS We developed a lectin-antibody ELISA kit using PhoSL to determine core-Fuc-Hpt levels in sera from colorectal or pancreatic cancer patients. 25861849 9 15 theme cell 1166:1169 arg1 lines 1171:1175 Hpt-transfected colorectal cancer cell lines 1132:1175 Hpt-transfected colorectal cancer cell lines 1132:1175 Hpt-transfected colorectal cancer cell lines produced significant amounts of core-Fuc-Hpt, suggesting that colorectal cancer tissues produce core-Fuc-Hpt. 25861849 7 16 theme Hpt 902:904 arg1 levels 879:884 RESULTS Serum levels 865:884 RESULTS Serum levels of AAL-reactive Hpt 865:904 RESULTS Serum levels of AAL-reactive Hpt are higher in pancreatic cancer patients, whereas those of PhoSL-reactive Hpt are higher in colorectal cancer patients. 25861849 8 17 theme ELISA 1117:1121 arg1 results 1123:1129 lectin-antibody ELISA results 1101:1129 lectin-antibody ELISA results 1101:1129 Mass spectrometry analyses of Hpt fucosylation levels were consistent with lectin-antibody ELISA results. 25861849 8 18 theme Mass 1026:1029 arg1 analyses 1044:1051 Mass spectrometry analyses 1026:1051 Mass spectrometry analyses of Hpt fucosylation levels 1026:1078 Mass spectrometry analyses of Hpt fucosylation levels were consistent with lectin-antibody ELISA results. 25861849 6 19 from patients 855:862 arg1 sera 813:816 sera 813:816 sera from colorectal or pancreatic cancer patients 813:862 METHODS We developed a lectin-antibody ELISA kit using PhoSL to determine core-Fuc-Hpt levels in sera from colorectal or pancreatic cancer patients. 25861849 6 19 from patients 855:862 arg1 levels 803:808 core-Fuc-Hpt levels 790:808 core-Fuc-Hpt levels in sera from colorectal or pancreatic cancer patients 790:862 METHODS We developed a lectin-antibody ELISA kit using PhoSL to determine core-Fuc-Hpt levels in sera from colorectal or pancreatic cancer patients. 25861849 8 20 theme Hpt 1056:1058 arg1 levels 1073:1078 Hpt fucosylation levels 1056:1078 Hpt fucosylation levels 1056:1078 Mass spectrometry analyses of Hpt fucosylation levels were consistent with lectin-antibody ELISA results. 25861849 0 21 theme ELISA 41:45 arg1 system 47:52 a novel lectin-antibody ELISA system 17:52 a novel lectin-antibody ELISA system 17:52 Establishment of a novel lectin-antibody ELISA system to determine core-fucosylated haptoglobin. 25861849 5 22 theme novel 598:602 arg1 lectin 631:636 Pholiota squarrosa lectin 612:636 Pholiota squarrosa lectin (PhoSL) 612:644 Recently, we identified a novel lectin, Pholiota squarrosa lectin (PhoSL), which specifically recognizes α1-6 fucosylation (core-fucosylation). 25861849 5 22 theme novel 598:602 arg1 lectin 604:609 a novel lectin 596:609 a novel lectin 596:609 Recently, we identified a novel lectin, Pholiota squarrosa lectin (PhoSL), which specifically recognizes α1-6 fucosylation (core-fucosylation). 25861849 9 23 theme Hpt-transfected 1132:1146 arg1 lines 1171:1175 Hpt-transfected colorectal cancer cell lines 1132:1175 Hpt-transfected colorectal cancer cell lines 1132:1175 Hpt-transfected colorectal cancer cell lines produced significant amounts of core-Fuc-Hpt, suggesting that colorectal cancer tissues produce core-Fuc-Hpt. 25861849 9 24 theme cancer 1159:1164 arg1 lines 1171:1175 Hpt-transfected colorectal cancer cell lines 1132:1175 Hpt-transfected colorectal cancer cell lines 1132:1175 Hpt-transfected colorectal cancer cell lines produced significant amounts of core-Fuc-Hpt, suggesting that colorectal cancer tissues produce core-Fuc-Hpt. 25861849 6 25 dep METHODS 716:722 arg1 developed 727:735 developed 727:735 developed a lectin-antibody ELISA kit using PhoSL to determine core-Fuc-Hpt levels in sera from colorectal or pancreatic cancer patients 727:862 METHODS We developed a lectin-antibody ELISA kit using PhoSL to determine core-Fuc-Hpt levels in sera from colorectal or pancreatic cancer patients. 25861849 1 26 theme BACKGROUND 97:106 arg1 biomarker 160:168 a novel cancer biomarker 145:168 a novel cancer biomarker that increases in various pathological conditions 145:218 BACKGROUND Fucosylated haptoglobin (Fuc-Hpt) is a novel cancer biomarker that increases in various pathological conditions. 25861849 1 26 theme BACKGROUND 97:106 arg1 Fuc-Hpt 133:139 Fuc-Hpt 133:139 Fuc-Hpt 133:139 BACKGROUND Fucosylated haptoglobin (Fuc-Hpt) is a novel cancer biomarker that increases in various pathological conditions. 25861849 1 26 theme BACKGROUND 97:106 arg1 haptoglobin 120:130 BACKGROUND Fucosylated haptoglobin 97:130 BACKGROUND Fucosylated haptoglobin (Fuc-Hpt) 97:140 BACKGROUND Fucosylated haptoglobin (Fuc-Hpt) is a novel cancer biomarker that increases in various pathological conditions. 25861849 7 27 theme AAL-reactive 889:900 arg1 Hpt 902:904 AAL-reactive Hpt 889:904 AAL-reactive Hpt 889:904 RESULTS Serum levels of AAL-reactive Hpt are higher in pancreatic cancer patients, whereas those of PhoSL-reactive Hpt are higher in colorectal cancer patients. 25861849 1 28 theme various 188:194 arg1 conditions 209:218 various pathological conditions 188:218 various pathological conditions 188:218 BACKGROUND Fucosylated haptoglobin (Fuc-Hpt) is a novel cancer biomarker that increases in various pathological conditions. 25861849 8 29 theme fucosylation 1060:1071 arg1 levels 1073:1078 Hpt fucosylation levels 1056:1078 Hpt fucosylation levels 1056:1078 Mass spectrometry analyses of Hpt fucosylation levels were consistent with lectin-antibody ELISA results. 25861849 1 30 theme Fucosylated 108:118 arg1 biomarker 160:168 a novel cancer biomarker 145:168 a novel cancer biomarker that increases in various pathological conditions 145:218 BACKGROUND Fucosylated haptoglobin (Fuc-Hpt) is a novel cancer biomarker that increases in various pathological conditions. 25861849 1 30 theme Fucosylated 108:118 arg1 Fuc-Hpt 133:139 Fuc-Hpt 133:139 Fuc-Hpt 133:139 BACKGROUND Fucosylated haptoglobin (Fuc-Hpt) is a novel cancer biomarker that increases in various pathological conditions. 25861849 1 30 theme Fucosylated 108:118 arg1 haptoglobin 120:130 BACKGROUND Fucosylated haptoglobin 97:130 BACKGROUND Fucosylated haptoglobin (Fuc-Hpt) 97:140 BACKGROUND Fucosylated haptoglobin (Fuc-Hpt) is a novel cancer biomarker that increases in various pathological conditions. 25861849 7 31 theme Serum 873:877 arg1 levels 879:884 RESULTS Serum levels 865:884 RESULTS Serum levels of AAL-reactive Hpt 865:904 RESULTS Serum levels of AAL-reactive Hpt are higher in pancreatic cancer patients, whereas those of PhoSL-reactive Hpt are higher in colorectal cancer patients. 25861849 3 32 theme N/O-linked 444:453 arg1 glycans 455:461 N/O-linked glycans 444:461 N/O-linked glycans 444:461 AAL recognizes both α1-3/1-4 and α1-6 fucosylation on N/O-linked glycans. 25861849 0 33 theme novel 19:23 arg1 system 47:52 a novel lectin-antibody ELISA system 17:52 a novel lectin-antibody ELISA system 17:52 Establishment of a novel lectin-antibody ELISA system to determine core-fucosylated haptoglobin. 25861849 5 34 theme Pholiota 612:619 arg1 lectin 631:636 Pholiota squarrosa lectin 612:636 Pholiota squarrosa lectin (PhoSL) 612:644 Recently, we identified a novel lectin, Pholiota squarrosa lectin (PhoSL), which specifically recognizes α1-6 fucosylation (core-fucosylation). 25861849 5 34 theme Pholiota 612:619 arg1 lectin 604:609 a novel lectin 596:609 a novel lectin 596:609 Recently, we identified a novel lectin, Pholiota squarrosa lectin (PhoSL), which specifically recognizes α1-6 fucosylation (core-fucosylation). 25861849 5 34 theme Pholiota 612:619 arg1 PhoSL 639:643 PhoSL 639:643 PhoSL 639:643 Recently, we identified a novel lectin, Pholiota squarrosa lectin (PhoSL), which specifically recognizes α1-6 fucosylation (core-fucosylation). 25861849 10 35 theme surrounding 1374:1384 arg1 cells 1386:1390 the surrounding cells 1370:1390 the surrounding cells 1370:1390 CONCLUSIONS These differences in Fuc-Hpt patterns might depend on cancer cells and the surrounding cells, which produce Hpt. 25861849 7 36 theme colorectal 998:1007 arg1 patients 1016:1023 colorectal cancer patients 998:1023 colorectal cancer patients 998:1023 RESULTS Serum levels of AAL-reactive Hpt are higher in pancreatic cancer patients, whereas those of PhoSL-reactive Hpt are higher in colorectal cancer patients. 25861849 4 37 theme fucosylation 470:481 arg1 types 483:487 These fucosylation types 464:487 These fucosylation types 464:487 These fucosylation types differ in biological function, and in regulation by different fucosyltransferases. 25861849 7 38 theme RESULTS 865:871 arg1 levels 879:884 RESULTS Serum levels 865:884 RESULTS Serum levels of AAL-reactive Hpt 865:904 RESULTS Serum levels of AAL-reactive Hpt are higher in pancreatic cancer patients, whereas those of PhoSL-reactive Hpt are higher in colorectal cancer patients. 25861849 9 39 theme significant 1186:1196 arg1 core-Fuc-Hpt 1209:1220 core-Fuc-Hpt 1209:1220 core-Fuc-Hpt 1209:1220 Hpt-transfected colorectal cancer cell lines produced significant amounts of core-Fuc-Hpt, suggesting that colorectal cancer tissues produce core-Fuc-Hpt. 25861849 9 39 theme significant 1186:1196 arg1 amounts 1198:1204 significant amounts 1186:1204 significant amounts of core-Fuc-Hpt 1186:1220 Hpt-transfected colorectal cancer cell lines produced significant amounts of core-Fuc-Hpt, suggesting that colorectal cancer tissues produce core-Fuc-Hpt. 25861849 3 40 theme α1-6 423:426 arg1 fucosylation 428:439 α1-6 fucosylation 423:439 α1-6 fucosylation 423:439 AAL recognizes both α1-3/1-4 and α1-6 fucosylation on N/O-linked glycans. 25861849 8 41 with consistent 1085:1094 arg1 results 1123:1129 lectin-antibody ELISA results 1101:1129 lectin-antibody ELISA results 1101:1129 Mass spectrometry analyses of Hpt fucosylation levels were consistent with lectin-antibody ELISA results. 25861849 2 42 theme lectin-antibody 257:271 arg1 assay 273:277 a Fuc-Hpt lectin-antibody assay 247:277 a Fuc-Hpt lectin-antibody assay 247:277 We previously established a Fuc-Hpt lectin-antibody assay using Aleuria aurantia lectin (AAL), and applied this to diagnose several diseases, including various cancers. 25861849 1 43 theme pathological 196:207 arg1 conditions 209:218 various pathological conditions 188:218 various pathological conditions 188:218 BACKGROUND Fucosylated haptoglobin (Fuc-Hpt) is a novel cancer biomarker that increases in various pathological conditions. 25861849 0 44 theme lectin-antibody 25:39 arg1 system 47:52 a novel lectin-antibody ELISA system 17:52 a novel lectin-antibody ELISA system 17:52 Establishment of a novel lectin-antibody ELISA system to determine core-fucosylated haptoglobin. 25861849 8 45 theme spectrometry 1031:1042 arg1 analyses 1044:1051 Mass spectrometry analyses 1026:1051 Mass spectrometry analyses of Hpt fucosylation levels 1026:1078 Mass spectrometry analyses of Hpt fucosylation levels were consistent with lectin-antibody ELISA results. 25861849 2 46 theme Fuc-Hpt 249:255 arg1 assay 273:277 a Fuc-Hpt lectin-antibody assay 247:277 a Fuc-Hpt lectin-antibody assay 247:277 We previously established a Fuc-Hpt lectin-antibody assay using Aleuria aurantia lectin (AAL), and applied this to diagnose several diseases, including various cancers. 25861849 8 47 theme lectin-antibody 1101:1115 arg1 results 1123:1129 lectin-antibody ELISA results 1101:1129 lectin-antibody ELISA results 1101:1129 Mass spectrometry analyses of Hpt fucosylation levels were consistent with lectin-antibody ELISA results. 25861849 4 48 theme different 541:549 arg1 fucosyltransferases 551:569 different fucosyltransferases 541:569 different fucosyltransferases 541:569 These fucosylation types differ in biological function, and in regulation by different fucosyltransferases. 25861849 10 49 from differences 1305:1315 arg1 patterns 1328:1335 Fuc-Hpt patterns 1320:1335 Fuc-Hpt patterns 1320:1335 CONCLUSIONS These differences in Fuc-Hpt patterns might depend on cancer cells and the surrounding cells, which produce Hpt. 25861849 6 50 theme core-Fuc-Hpt 790:801 arg1 levels 803:808 core-Fuc-Hpt levels 790:808 core-Fuc-Hpt levels in sera from colorectal or pancreatic cancer patients 790:862 METHODS We developed a lectin-antibody ELISA kit using PhoSL to determine core-Fuc-Hpt levels in sera from colorectal or pancreatic cancer patients. 25861849 0 51 theme system 47:52 arg1 Establishment 0:12 Establishment 0:12 Establishment of a novel lectin-antibody ELISA system 0:52 Establishment of a novel lectin-antibody ELISA system to determine core-fucosylated haptoglobin. 25861849 3 52 link N/O-linked 444:453 arg1 glycans 455:461 N/O-linked glycans 444:461 N/O-linked glycans 444:461 AAL recognizes both α1-3/1-4 and α1-6 fucosylation on N/O-linked glycans. 25861849 2 53 theme several 345:351 arg1 diseases 353:360 several diseases 345:360 several diseases 345:360 We previously established a Fuc-Hpt lectin-antibody assay using Aleuria aurantia lectin (AAL), and applied this to diagnose several diseases, including various cancers. 25861849 2 53 theme several 345:351 arg1 cancers 381:387 various cancers 373:387 various cancers 373:387 We previously established a Fuc-Hpt lectin-antibody assay using Aleuria aurantia lectin (AAL), and applied this to diagnose several diseases, including various cancers. 25861849 7 54 theme PhoSL-reactive 965:978 arg1 Hpt 980:982 PhoSL-reactive Hpt 965:982 PhoSL-reactive Hpt 965:982 RESULTS Serum levels of AAL-reactive Hpt are higher in pancreatic cancer patients, whereas those of PhoSL-reactive Hpt are higher in colorectal cancer patients. 25861849 6 55 theme colorectal 823:832 arg1 patients 855:862 colorectal or pancreatic cancer patients 823:862 patients 855:862 METHODS We developed a lectin-antibody ELISA kit using PhoSL to determine core-Fuc-Hpt levels in sera from colorectal or pancreatic cancer patients. 25861849 2 56 theme aurantia 293:300 arg1 AAL 310:312 AAL 310:312 AAL 310:312 We previously established a Fuc-Hpt lectin-antibody assay using Aleuria aurantia lectin (AAL), and applied this to diagnose several diseases, including various cancers. 25861849 2 56 theme aurantia 293:300 arg1 lectin 302:307 Aleuria aurantia lectin 285:307 Aleuria aurantia lectin (AAL) 285:313 We previously established a Fuc-Hpt lectin-antibody assay using Aleuria aurantia lectin (AAL), and applied this to diagnose several diseases, including various cancers. 25861849 7 57 theme cancer 1009:1014 arg1 patients 1016:1023 colorectal cancer patients 998:1023 colorectal cancer patients 998:1023 RESULTS Serum levels of AAL-reactive Hpt are higher in pancreatic cancer patients, whereas those of PhoSL-reactive Hpt are higher in colorectal cancer patients. 25861849 6 58 from levels 803:808 arg1 sera 813:816 sera 813:816 sera from colorectal or pancreatic cancer patients 813:862 METHODS We developed a lectin-antibody ELISA kit using PhoSL to determine core-Fuc-Hpt levels in sera from colorectal or pancreatic cancer patients. 25861849 6 58 from levels 803:808 arg1 patients 855:862 colorectal or pancreatic cancer patients 823:862 patients 855:862 METHODS We developed a lectin-antibody ELISA kit using PhoSL to determine core-Fuc-Hpt levels in sera from colorectal or pancreatic cancer patients. 25861849 10 59 dep CONCLUSIONS 1287:1297 arg1 depend 1343:1348 depend 1343:1348 might depend on cancer cells and the surrounding cells, which produce Hpt 1337:1409 CONCLUSIONS These differences in Fuc-Hpt patterns might depend on cancer cells and the surrounding cells, which produce Hpt. 25861849 2 60 theme Aleuria 285:291 arg1 AAL 310:312 AAL 310:312 AAL 310:312 We previously established a Fuc-Hpt lectin-antibody assay using Aleuria aurantia lectin (AAL), and applied this to diagnose several diseases, including various cancers. 25861849 2 60 theme Aleuria 285:291 arg1 lectin 302:307 Aleuria aurantia lectin 285:307 Aleuria aurantia lectin (AAL) 285:313 We previously established a Fuc-Hpt lectin-antibody assay using Aleuria aurantia lectin (AAL), and applied this to diagnose several diseases, including various cancers. 25861849 1 61 theme cancer 153:158 arg1 haptoglobin 120:130 BACKGROUND Fucosylated haptoglobin 97:130 BACKGROUND Fucosylated haptoglobin (Fuc-Hpt) 97:140 BACKGROUND Fucosylated haptoglobin (Fuc-Hpt) is a novel cancer biomarker that increases in various pathological conditions. 25861849 1 61 theme cancer 153:158 arg1 biomarker 160:168 a novel cancer biomarker 145:168 a novel cancer biomarker that increases in various pathological conditions 145:218 BACKGROUND Fucosylated haptoglobin (Fuc-Hpt) is a novel cancer biomarker that increases in various pathological conditions. 25861849 0 62 theme core-fucosylated 67:82 arg1 haptoglobin 84:94 core-fucosylated haptoglobin 67:94 core-fucosylated haptoglobin 67:94 Establishment of a novel lectin-antibody ELISA system to determine core-fucosylated haptoglobin. 25861849 9 63 theme colorectal 1239:1248 arg1 tissues 1257:1263 colorectal cancer tissues 1239:1263 colorectal cancer tissues 1239:1263 Hpt-transfected colorectal cancer cell lines produced significant amounts of core-Fuc-Hpt, suggesting that colorectal cancer tissues produce core-Fuc-Hpt. 25861849 1 64 theme novel 147:151 arg1 haptoglobin 120:130 BACKGROUND Fucosylated haptoglobin 97:130 BACKGROUND Fucosylated haptoglobin (Fuc-Hpt) 97:140 BACKGROUND Fucosylated haptoglobin (Fuc-Hpt) is a novel cancer biomarker that increases in various pathological conditions. 25861849 1 64 theme novel 147:151 arg1 biomarker 160:168 a novel cancer biomarker 145:168 a novel cancer biomarker that increases in various pathological conditions 145:218 BACKGROUND Fucosylated haptoglobin (Fuc-Hpt) is a novel cancer biomarker that increases in various pathological conditions. 25861849 8 65 theme levels 1073:1078 arg1 analyses 1044:1051 Mass spectrometry analyses 1026:1051 Mass spectrometry analyses of Hpt fucosylation levels 1026:1078 Mass spectrometry analyses of Hpt fucosylation levels were consistent with lectin-antibody ELISA results. 25861849 7 66 dep higher 910:915 arg1 whereas 948:954 whereas 948:954 whereas 948:954 RESULTS Serum levels of AAL-reactive Hpt are higher in pancreatic cancer patients, whereas those of PhoSL-reactive Hpt are higher in colorectal cancer patients. 25861849 3 67 from α1-3/1-4 410:417 arg1 glycans 455:461 N/O-linked glycans 444:461 N/O-linked glycans 444:461 AAL recognizes both α1-3/1-4 and α1-6 fucosylation on N/O-linked glycans. 25861849 9 68 theme cancer 1250:1255 arg1 tissues 1257:1263 colorectal cancer tissues 1239:1263 colorectal cancer tissues 1239:1263 Hpt-transfected colorectal cancer cell lines produced significant amounts of core-Fuc-Hpt, suggesting that colorectal cancer tissues produce core-Fuc-Hpt. 25861849 2 69 theme various 373:379 arg1 cancers 381:387 various cancers 373:387 various cancers 373:387 We previously established a Fuc-Hpt lectin-antibody assay using Aleuria aurantia lectin (AAL), and applied this to diagnose several diseases, including various cancers. 25861849 7 70 theme pancreatic 920:929 arg1 patients 938:945 pancreatic cancer patients 920:945 pancreatic cancer patients 920:945 RESULTS Serum levels of AAL-reactive Hpt are higher in pancreatic cancer patients, whereas those of PhoSL-reactive Hpt are higher in colorectal cancer patients. 26492012 6 0 theme α-synuclein 976:986 arg1 toxicity 964:971 the toxicity 960:971 the toxicity of α-synuclein that was exogenously added to cells in culture 960:1033 O-GlcNAcylation is also shown to affect the phosphorylation of α-synuclein in vitro and block the toxicity of α-synuclein that was exogenously added to cells in culture. 26492012 5 1 theme single 685:690 arg1 modification 692:703 this single modification 680:703 this single modification 680:703 We show that this single modification has a notable and substoichiometric inhibitory effect on α-synuclein aggregation, while not affecting the membrane binding or bending properties of α-synuclein. 26492012 1 2 theme neurodegenerative 173:189 arg1 diseases 191:198 neurodegenerative diseases 173:198 neurodegenerative diseases 173:198 Several aggregation-prone proteins associated with neurodegenerative diseases can be modified by O-linked N-acetyl-glucosamine (O-GlcNAc) in vivo. 26492012 5 3 from effect 752:757 arg1 aggregation 774:784 α-synuclein aggregation 762:784 α-synuclein aggregation 762:784 We show that this single modification has a notable and substoichiometric inhibitory effect on α-synuclein aggregation, while not affecting the membrane binding or bending properties of α-synuclein. 26492012 0 4 theme α-synuclein 73:83 arg1 toxicity 49:56 toxicity 49:56 toxicity 49:56 O-GlcNAc modification blocks the aggregation and toxicity of the protein α-synuclein associated with Parkinson's disease. 26492012 0 4 theme α-synuclein 73:83 arg1 aggregation 33:43 aggregation 33:43 aggregation 33:43 O-GlcNAc modification blocks the aggregation and toxicity of the protein α-synuclein associated with Parkinson's disease. 26492012 4 5 theme unmodified 528:537 arg1 α-synuclein 539:549 unmodified α-synuclein 528:549 unmodified α-synuclein 528:549 Here, we use synthetic protein chemistry to generate both unmodified α-synuclein and α-synuclein bearing a site-specific O-GlcNAc modification at the physiologically relevant threonine residue 72. 26492012 7 6 theme protein 1202:1208 arg1 aggregation 1210:1220 protein aggregation 1202:1220 protein aggregation 1202:1220 These results suggest that increasing O-GlcNAcylation may slow the progression of synucleinopathies and further support a general function for O-GlcNAc in preventing protein aggregation. 26492012 1 7 link O-linked 219:226 arg1 N-acetyl-glucosamine 228:247 O-linked N-acetyl-glucosamine 219:247 O-linked N-acetyl-glucosamine (O-GlcNAc) 219:258 Several aggregation-prone proteins associated with neurodegenerative diseases can be modified by O-linked N-acetyl-glucosamine (O-GlcNAc) in vivo. 26492012 1 7 link O-linked 219:226 arg1 O-GlcNAc 250:257 O-GlcNAc 250:257 O-GlcNAc 250:257 Several aggregation-prone proteins associated with neurodegenerative diseases can be modified by O-linked N-acetyl-glucosamine (O-GlcNAc) in vivo. 26492012 4 8 theme relevant 636:643 arg1 residue 655:661 the physiologically relevant threonine residue 72 616:664 the physiologically relevant threonine residue 72 616:664 Here, we use synthetic protein chemistry to generate both unmodified α-synuclein and α-synuclein bearing a site-specific O-GlcNAc modification at the physiologically relevant threonine residue 72. 26492012 4 9 theme synthetic 483:491 arg1 chemistry 501:509 synthetic protein chemistry 483:509 synthetic protein chemistry 483:509 Here, we use synthetic protein chemistry to generate both unmodified α-synuclein and α-synuclein bearing a site-specific O-GlcNAc modification at the physiologically relevant threonine residue 72. 26492012 5 10 theme bending 831:837 arg1 properties 839:848 the membrane binding or bending properties 807:848 properties 839:848 We show that this single modification has a notable and substoichiometric inhibitory effect on α-synuclein aggregation, while not affecting the membrane binding or bending properties of α-synuclein. 26492012 5 11 contain has 705:707 arg1 modification 692:703 this single modification 680:703 this single modification 680:703 We show that this single modification has a notable and substoichiometric inhibitory effect on α-synuclein aggregation, while not affecting the membrane binding or bending properties of α-synuclein. 26492012 5 11 contain has 705:707 arg2 effect 752:757 a notable and substoichiometric inhibitory effect 709:757 a notable and substoichiometric inhibitory effect on α-synuclein aggregation 709:784 We show that this single modification has a notable and substoichiometric inhibitory effect on α-synuclein aggregation, while not affecting the membrane binding or bending properties of α-synuclein. 26492012 4 12 theme protein 493:499 arg1 chemistry 501:509 synthetic protein chemistry 483:509 synthetic protein chemistry 483:509 Here, we use synthetic protein chemistry to generate both unmodified α-synuclein and α-synuclein bearing a site-specific O-GlcNAc modification at the physiologically relevant threonine residue 72. 26492012 7 13 theme general 1158:1164 arg1 function 1166:1173 a general function 1156:1173 a general function for O-GlcNAc in preventing protein aggregation 1156:1220 These results suggest that increasing O-GlcNAcylation may slow the progression of synucleinopathies and further support a general function for O-GlcNAc in preventing protein aggregation. 26492012 0 14 theme O-GlcNAc 0:7 arg1 modification 9:20 O-GlcNAc modification 0:20 O-GlcNAc modification 0:20 O-GlcNAc modification blocks the aggregation and toxicity of the protein α-synuclein associated with Parkinson's disease. 26492012 4 15 theme site-specific 577:589 arg1 modification 600:611 a site-specific O-GlcNAc modification 575:611 a site-specific O-GlcNAc modification 575:611 Here, we use synthetic protein chemistry to generate both unmodified α-synuclein and α-synuclein bearing a site-specific O-GlcNAc modification at the physiologically relevant threonine residue 72. 26492012 2 16 theme aggregating 316:326 arg1 proteins 282:289 these proteins 276:289 these proteins 276:289 One of these proteins, α-synuclein, is a toxic aggregating protein associated with synucleinopathies, including Parkinson's disease. 26492012 2 16 theme aggregating 316:326 arg1 One 269:271 One 269:271 One 269:271 One of these proteins, α-synuclein, is a toxic aggregating protein associated with synucleinopathies, including Parkinson's disease. 26492012 2 16 theme aggregating 316:326 arg1 protein 328:334 a toxic aggregating protein 308:334 a toxic aggregating protein associated with synucleinopathies, including Parkinson's disease 308:399 One of these proteins, α-synuclein, is a toxic aggregating protein associated with synucleinopathies, including Parkinson's disease. 26492012 2 17 theme toxic 310:314 arg1 proteins 282:289 these proteins 276:289 these proteins 276:289 One of these proteins, α-synuclein, is a toxic aggregating protein associated with synucleinopathies, including Parkinson's disease. 26492012 2 17 theme toxic 310:314 arg1 One 269:271 One 269:271 One 269:271 One of these proteins, α-synuclein, is a toxic aggregating protein associated with synucleinopathies, including Parkinson's disease. 26492012 2 17 theme toxic 310:314 arg1 protein 328:334 a toxic aggregating protein 308:334 a toxic aggregating protein associated with synucleinopathies, including Parkinson's disease 308:399 One of these proteins, α-synuclein, is a toxic aggregating protein associated with synucleinopathies, including Parkinson's disease. 26492012 1 18 theme O-linked 219:226 arg1 N-acetyl-glucosamine 228:247 O-linked N-acetyl-glucosamine 219:247 O-linked N-acetyl-glucosamine (O-GlcNAc) 219:258 Several aggregation-prone proteins associated with neurodegenerative diseases can be modified by O-linked N-acetyl-glucosamine (O-GlcNAc) in vivo. 26492012 1 18 theme O-linked 219:226 arg1 O-GlcNAc 250:257 O-GlcNAc 250:257 O-GlcNAc 250:257 Several aggregation-prone proteins associated with neurodegenerative diseases can be modified by O-linked N-acetyl-glucosamine (O-GlcNAc) in vivo. 26492012 6 19 from cells 1018:1022 arg1 culture 1027:1033 culture 1027:1033 culture 1027:1033 O-GlcNAcylation is also shown to affect the phosphorylation of α-synuclein in vitro and block the toxicity of α-synuclein that was exogenously added to cells in culture. 26492012 3 20 theme O-GlcNAcylation 425:439 arg1 clear 463:467 clear 463:467 clear 463:467 However, the effect of O-GlcNAcylation on α-synuclein is not clear. 26492012 3 20 theme O-GlcNAcylation 425:439 arg1 effect 415:420 the effect 411:420 the effect of O-GlcNAcylation on α-synuclein 411:454 However, the effect of O-GlcNAcylation on α-synuclein is not clear. 26492012 4 21 theme O-GlcNAc 591:598 arg1 modification 600:611 a site-specific O-GlcNAc modification 575:611 a site-specific O-GlcNAc modification 575:611 Here, we use synthetic protein chemistry to generate both unmodified α-synuclein and α-synuclein bearing a site-specific O-GlcNAc modification at the physiologically relevant threonine residue 72. 26492012 5 22 theme α-synuclein 762:772 arg1 aggregation 774:784 α-synuclein aggregation 762:784 α-synuclein aggregation 762:784 We show that this single modification has a notable and substoichiometric inhibitory effect on α-synuclein aggregation, while not affecting the membrane binding or bending properties of α-synuclein. 26492012 6 23 theme α-synuclein 929:939 arg1 phosphorylation 910:924 the phosphorylation 906:924 the phosphorylation of α-synuclein 906:939 O-GlcNAcylation is also shown to affect the phosphorylation of α-synuclein in vitro and block the toxicity of α-synuclein that was exogenously added to cells in culture. 26492012 5 24 theme notable 711:717 arg1 effect 752:757 a notable and substoichiometric inhibitory effect 709:757 a notable and substoichiometric inhibitory effect on α-synuclein aggregation 709:784 We show that this single modification has a notable and substoichiometric inhibitory effect on α-synuclein aggregation, while not affecting the membrane binding or bending properties of α-synuclein. 26492012 5 25 theme α-synuclein 853:863 arg1 binding 820:826 the membrane binding or bending properties 807:848 binding 820:826 We show that this single modification has a notable and substoichiometric inhibitory effect on α-synuclein aggregation, while not affecting the membrane binding or bending properties of α-synuclein. 26492012 5 25 theme α-synuclein 853:863 arg1 properties 839:848 the membrane binding or bending properties 807:848 properties 839:848 We show that this single modification has a notable and substoichiometric inhibitory effect on α-synuclein aggregation, while not affecting the membrane binding or bending properties of α-synuclein. 26492012 7 26 theme synucleinopathies 1118:1134 arg1 progression 1103:1113 the progression 1099:1113 the progression of synucleinopathies 1099:1134 These results suggest that increasing O-GlcNAcylation may slow the progression of synucleinopathies and further support a general function for O-GlcNAc in preventing protein aggregation. 26492012 0 27 dep aggregation 33:43 arg1 the 29:31 the 29:31 the 29:31 O-GlcNAc modification blocks the aggregation and toxicity of the protein α-synuclein associated with Parkinson's disease. 26492012 7 28 theme increasing 1063:1072 arg1 O-GlcNAcylation 1074:1088 increasing O-GlcNAcylation 1063:1088 increasing O-GlcNAcylation 1063:1088 These results suggest that increasing O-GlcNAcylation may slow the progression of synucleinopathies and further support a general function for O-GlcNAc in preventing protein aggregation. 26492012 1 29 mod modified 207:214 arg3 O-GlcNAc 250:257 O-GlcNAc 250:257 O-GlcNAc 250:257 Several aggregation-prone proteins associated with neurodegenerative diseases can be modified by O-linked N-acetyl-glucosamine (O-GlcNAc) in vivo. 26492012 1 29 mod modified 207:214 arg1 proteins 148:155 Several aggregation-prone proteins 122:155 Several aggregation-prone proteins associated with neurodegenerative diseases 122:198 Several aggregation-prone proteins associated with neurodegenerative diseases can be modified by O-linked N-acetyl-glucosamine (O-GlcNAc) in vivo. 26492012 1 29 mod modified 207:214 arg3 N-acetyl-glucosamine 228:247 O-linked N-acetyl-glucosamine 219:247 O-linked N-acetyl-glucosamine (O-GlcNAc) 219:258 Several aggregation-prone proteins associated with neurodegenerative diseases can be modified by O-linked N-acetyl-glucosamine (O-GlcNAc) in vivo. 26492012 5 30 theme substoichiometric 723:739 arg1 effect 752:757 a notable and substoichiometric inhibitory effect 709:757 a notable and substoichiometric inhibitory effect on α-synuclein aggregation 709:784 We show that this single modification has a notable and substoichiometric inhibitory effect on α-synuclein aggregation, while not affecting the membrane binding or bending properties of α-synuclein. 26492012 2 31 theme proteins 282:289 arg1 protein 328:334 a toxic aggregating protein 308:334 a toxic aggregating protein associated with synucleinopathies, including Parkinson's disease 308:399 One of these proteins, α-synuclein, is a toxic aggregating protein associated with synucleinopathies, including Parkinson's disease. 26492012 2 31 theme proteins 282:289 arg1 α-synuclein 292:302 α-synuclein 292:302 α-synuclein 292:302 One of these proteins, α-synuclein, is a toxic aggregating protein associated with synucleinopathies, including Parkinson's disease. 26492012 2 31 theme proteins 282:289 arg1 One 269:271 One 269:271 One 269:271 One of these proteins, α-synuclein, is a toxic aggregating protein associated with synucleinopathies, including Parkinson's disease. 26492012 2 31 theme proteins 282:289 arg1 proteins 282:289 these proteins 276:289 these proteins 276:289 One of these proteins, α-synuclein, is a toxic aggregating protein associated with synucleinopathies, including Parkinson's disease. 26492012 1 32 theme aggregation-prone 130:146 arg1 proteins 148:155 Several aggregation-prone proteins 122:155 Several aggregation-prone proteins associated with neurodegenerative diseases 122:198 Several aggregation-prone proteins associated with neurodegenerative diseases can be modified by O-linked N-acetyl-glucosamine (O-GlcNAc) in vivo. 26492012 5 33 theme inhibitory 741:750 arg1 effect 752:757 a notable and substoichiometric inhibitory effect 709:757 a notable and substoichiometric inhibitory effect on α-synuclein aggregation 709:784 We show that this single modification has a notable and substoichiometric inhibitory effect on α-synuclein aggregation, while not affecting the membrane binding or bending properties of α-synuclein. 26492012 4 34 theme threonine 645:653 arg1 residue 655:661 the physiologically relevant threonine residue 72 616:664 the physiologically relevant threonine residue 72 616:664 Here, we use synthetic protein chemistry to generate both unmodified α-synuclein and α-synuclein bearing a site-specific O-GlcNAc modification at the physiologically relevant threonine residue 72. 26492012 0 35 theme protein 65:71 arg1 α-synuclein 73:83 the protein α-synuclein 61:83 the protein α-synuclein associated with Parkinson's disease 61:119 O-GlcNAc modification blocks the aggregation and toxicity of the protein α-synuclein associated with Parkinson's disease. 26492012 1 36 theme Several 122:128 arg1 proteins 148:155 Several aggregation-prone proteins 122:155 Several aggregation-prone proteins associated with neurodegenerative diseases 122:198 Several aggregation-prone proteins associated with neurodegenerative diseases can be modified by O-linked N-acetyl-glucosamine (O-GlcNAc) in vivo. 26492012 5 37 theme membrane 811:818 arg1 binding 820:826 the membrane binding or bending properties 807:848 binding 820:826 We show that this single modification has a notable and substoichiometric inhibitory effect on α-synuclein aggregation, while not affecting the membrane binding or bending properties of α-synuclein. 26492012 3 38 from effect 415:420 arg1 α-synuclein 444:454 α-synuclein 444:454 α-synuclein 444:454 However, the effect of O-GlcNAcylation on α-synuclein is not clear. 26399441 5 0 theme lipid 745:749 arg1 biosynthesis 751:762 nucleotide and lipid biosynthesis 730:762 biosynthesis 751:762 Glycosylation activates G6PD activity and increases glucose flux through the PPP, thereby providing precursors for nucleotide and lipid biosynthesis, and reducing equivalents for antioxidant defense. 26399441 3 1 from advantage 375:383 arg1 cells 395:399 cancer cells 388:399 cancer cells 388:399 However, how the PPP is regulated to confer a selective growth advantage on cancer cells is not well understood. 26399441 7 2 theme lung 977:980 arg1 cancers 982:988 human lung cancers 971:988 human lung cancers 971:988 Importantly, G6PD glycosylation is increased in human lung cancers. 26399441 4 3 mod modified 537:544 arg1 enzyme 503:508 the rate-limiting enzyme 485:508 the rate-limiting enzyme of the PPP 485:519 Here we show that glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the PPP, is dynamically modified with an O-linked β-N-acetylglucosamine sugar in response to hypoxia. 26399441 4 3 mod modified 537:544 arg1 G6PD 478:481 G6PD 478:481 G6PD 478:481 Here we show that glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the PPP, is dynamically modified with an O-linked β-N-acetylglucosamine sugar in response to hypoxia. 26399441 4 3 mod modified 537:544 arg1 dehydrogenase 463:475 glucose-6-phosphate dehydrogenase 443:475 glucose-6-phosphate dehydrogenase (G6PD) 443:482 Here we show that glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the PPP, is dynamically modified with an O-linked β-N-acetylglucosamine sugar in response to hypoxia. 26399441 4 3 mod modified 537:544 arg3 sugar 585:589 an O-linked β-N-acetylglucosamine sugar 551:589 an O-linked β-N-acetylglucosamine sugar in response to hypoxia 551:612 Here we show that glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the PPP, is dynamically modified with an O-linked β-N-acetylglucosamine sugar in response to hypoxia. 26399441 8 4 theme mechanistic 1013:1023 arg1 understanding 1025:1037 a mechanistic understanding 1011:1037 a mechanistic understanding of how O-glycosylation directly regulates the PPP to confer a selective growth advantage to tumours 1011:1137 Our findings reveal a mechanistic understanding of how O-glycosylation directly regulates the PPP to confer a selective growth advantage to tumours. 26399441 5 5 theme reducing 769:776 arg1 equivalents 778:788 reducing equivalents 769:788 reducing equivalents 769:788 Glycosylation activates G6PD activity and increases glucose flux through the PPP, thereby providing precursors for nucleotide and lipid biosynthesis, and reducing equivalents for antioxidant defense. 26399441 6 6 theme tumor 901:905 arg1 growth 907:912 tumor growth 901:912 tumor growth 901:912 Blocking glycosylation of G6PD reduces cancer cell proliferation in vitro and impairs tumor growth in vivo. 26399441 5 7 theme G6PD 639:642 arg1 activity 644:651 G6PD activity 639:651 G6PD activity 639:651 Glycosylation activates G6PD activity and increases glucose flux through the PPP, thereby providing precursors for nucleotide and lipid biosynthesis, and reducing equivalents for antioxidant defense. 26399441 7 8 gly glycosylation 941:953 arg1 cancers 982:988 human lung cancers 971:988 human lung cancers 971:988 Importantly, G6PD glycosylation is increased in human lung cancers. 26399441 1 9 theme macromolecule 142:154 arg1 biosynthesis 156:167 macromolecule biosynthesis 142:167 macromolecule biosynthesis 142:167 The pentose phosphate pathway (PPP) plays a critical role in macromolecule biosynthesis and maintaining cellular redox homoeostasis in rapidly proliferating cells. 26399441 4 10 theme O-linked 554:561 arg1 sugar 585:589 an O-linked β-N-acetylglucosamine sugar 551:589 an O-linked β-N-acetylglucosamine sugar in response to hypoxia 551:612 Here we show that glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the PPP, is dynamically modified with an O-linked β-N-acetylglucosamine sugar in response to hypoxia. 26399441 4 11 theme glucose-6-phosphate 443:461 arg1 enzyme 503:508 the rate-limiting enzyme 485:508 the rate-limiting enzyme of the PPP 485:519 Here we show that glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the PPP, is dynamically modified with an O-linked β-N-acetylglucosamine sugar in response to hypoxia. 26399441 4 11 theme glucose-6-phosphate 443:461 arg1 G6PD 478:481 G6PD 478:481 G6PD 478:481 Here we show that glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the PPP, is dynamically modified with an O-linked β-N-acetylglucosamine sugar in response to hypoxia. 26399441 4 11 theme glucose-6-phosphate 443:461 arg1 dehydrogenase 463:475 glucose-6-phosphate dehydrogenase 443:475 glucose-6-phosphate dehydrogenase (G6PD) 443:482 Here we show that glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the PPP, is dynamically modified with an O-linked β-N-acetylglucosamine sugar in response to hypoxia. 26399441 5 12 theme nucleotide 730:739 arg1 biosynthesis 751:762 nucleotide and lipid biosynthesis 730:762 biosynthesis 751:762 Glycosylation activates G6PD activity and increases glucose flux through the PPP, thereby providing precursors for nucleotide and lipid biosynthesis, and reducing equivalents for antioxidant defense. 26399441 2 13 theme cancer 304:309 arg1 types 295:299 several types 287:299 several types of cancer 287:309 Upregulation of the PPP has been shown in several types of cancer. 26399441 6 14 gly glycosylation 824:836 arg1 G6PD 841:844 G6PD 841:844 G6PD 841:844 Blocking glycosylation of G6PD reduces cancer cell proliferation in vitro and impairs tumor growth in vivo. 26399441 3 15 theme selective 358:366 arg1 advantage 375:383 a selective growth advantage 356:383 a selective growth advantage on cancer cells 356:399 However, how the PPP is regulated to confer a selective growth advantage on cancer cells is not well understood. 26399441 4 16 theme PPP 517:519 arg1 enzyme 503:508 the rate-limiting enzyme 485:508 the rate-limiting enzyme of the PPP 485:519 Here we show that glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the PPP, is dynamically modified with an O-linked β-N-acetylglucosamine sugar in response to hypoxia. 26399441 4 16 theme PPP 517:519 arg1 dehydrogenase 463:475 glucose-6-phosphate dehydrogenase 443:475 glucose-6-phosphate dehydrogenase (G6PD) 443:482 Here we show that glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the PPP, is dynamically modified with an O-linked β-N-acetylglucosamine sugar in response to hypoxia. 26399441 1 17 theme pentose 85:91 arg1 PPP 112:114 PPP 112:114 PPP 112:114 The pentose phosphate pathway (PPP) plays a critical role in macromolecule biosynthesis and maintaining cellular redox homoeostasis in rapidly proliferating cells. 26399441 1 17 theme pentose 85:91 arg1 pathway 103:109 The pentose phosphate pathway 81:109 The pentose phosphate pathway (PPP) 81:115 The pentose phosphate pathway (PPP) plays a critical role in macromolecule biosynthesis and maintaining cellular redox homoeostasis in rapidly proliferating cells. 26399441 5 18 theme antioxidant 794:804 arg1 defense 806:812 antioxidant defense 794:812 antioxidant defense 794:812 Glycosylation activates G6PD activity and increases glucose flux through the PPP, thereby providing precursors for nucleotide and lipid biosynthesis, and reducing equivalents for antioxidant defense. 26399441 1 19 theme phosphate 93:101 arg1 PPP 112:114 PPP 112:114 PPP 112:114 The pentose phosphate pathway (PPP) plays a critical role in macromolecule biosynthesis and maintaining cellular redox homoeostasis in rapidly proliferating cells. 26399441 1 19 theme phosphate 93:101 arg1 pathway 103:109 The pentose phosphate pathway 81:109 The pentose phosphate pathway (PPP) 81:115 The pentose phosphate pathway (PPP) plays a critical role in macromolecule biosynthesis and maintaining cellular redox homoeostasis in rapidly proliferating cells. 26399441 1 20 theme cellular 185:192 arg1 homoeostasis 200:211 cellular redox homoeostasis 185:211 cellular redox homoeostasis in rapidly proliferating cells 185:242 The pentose phosphate pathway (PPP) plays a critical role in macromolecule biosynthesis and maintaining cellular redox homoeostasis in rapidly proliferating cells. 26399441 0 21 theme G6PD 19:22 arg1 O-GlcNAcylation 0:14 O-GlcNAcylation 0:14 O-GlcNAcylation of G6PD 0:22 O-GlcNAcylation of G6PD promotes the pentose phosphate pathway and tumor growth. 26399441 2 22 theme several 287:293 arg1 types 295:299 several types 287:299 several types of cancer 287:309 Upregulation of the PPP has been shown in several types of cancer. 26399441 1 23 theme redox 194:198 arg1 homoeostasis 200:211 cellular redox homoeostasis 185:211 cellular redox homoeostasis in rapidly proliferating cells 185:242 The pentose phosphate pathway (PPP) plays a critical role in macromolecule biosynthesis and maintaining cellular redox homoeostasis in rapidly proliferating cells. 26399441 0 24 theme pentose 37:43 arg1 pathway 55:61 the pentose phosphate pathway 33:61 the pentose phosphate pathway 33:61 O-GlcNAcylation of G6PD promotes the pentose phosphate pathway and tumor growth. 26399441 6 25 theme cell 861:864 arg1 proliferation 866:878 cancer cell proliferation 854:878 cancer cell proliferation 854:878 Blocking glycosylation of G6PD reduces cancer cell proliferation in vitro and impairs tumor growth in vivo. 26399441 3 26 theme cancer 388:393 arg1 cells 395:399 cancer cells 388:399 cancer cells 388:399 However, how the PPP is regulated to confer a selective growth advantage on cancer cells is not well understood. 26399441 4 27 theme rate-limiting 489:501 arg1 enzyme 503:508 the rate-limiting enzyme 485:508 the rate-limiting enzyme of the PPP 485:519 Here we show that glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the PPP, is dynamically modified with an O-linked β-N-acetylglucosamine sugar in response to hypoxia. 26399441 4 27 theme rate-limiting 489:501 arg1 dehydrogenase 463:475 glucose-6-phosphate dehydrogenase 443:475 glucose-6-phosphate dehydrogenase (G6PD) 443:482 Here we show that glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the PPP, is dynamically modified with an O-linked β-N-acetylglucosamine sugar in response to hypoxia. 26399441 6 28 theme cancer 854:859 arg1 proliferation 866:878 cancer cell proliferation 854:878 cancer cell proliferation 854:878 Blocking glycosylation of G6PD reduces cancer cell proliferation in vitro and impairs tumor growth in vivo. 26399441 1 29 from homoeostasis 200:211 arg1 cells 238:242 rapidly proliferating cells 216:242 rapidly proliferating cells 216:242 The pentose phosphate pathway (PPP) plays a critical role in macromolecule biosynthesis and maintaining cellular redox homoeostasis in rapidly proliferating cells. 26399441 3 30 theme growth 368:373 arg1 advantage 375:383 a selective growth advantage 356:383 a selective growth advantage on cancer cells 356:399 However, how the PPP is regulated to confer a selective growth advantage on cancer cells is not well understood. 26399441 8 31 theme growth 1111:1116 arg1 advantage 1118:1126 a selective growth advantage 1099:1126 a selective growth advantage to tumours 1099:1137 Our findings reveal a mechanistic understanding of how O-glycosylation directly regulates the PPP to confer a selective growth advantage to tumours. 26399441 4 32 link O-linked 554:561 arg1 sugar 585:589 an O-linked β-N-acetylglucosamine sugar 551:589 an O-linked β-N-acetylglucosamine sugar in response to hypoxia 551:612 Here we show that glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the PPP, is dynamically modified with an O-linked β-N-acetylglucosamine sugar in response to hypoxia. 26399441 0 33 theme phosphate 45:53 arg1 pathway 55:61 the pentose phosphate pathway 33:61 the pentose phosphate pathway 33:61 O-GlcNAcylation of G6PD promotes the pentose phosphate pathway and tumor growth. 26399441 8 34 theme selective 1101:1109 arg1 advantage 1118:1126 a selective growth advantage 1099:1126 a selective growth advantage to tumours 1099:1137 Our findings reveal a mechanistic understanding of how O-glycosylation directly regulates the PPP to confer a selective growth advantage to tumours. 26399441 6 35 theme G6PD 841:844 arg1 glycosylation 824:836 Blocking glycosylation 815:836 Blocking glycosylation of G6PD 815:844 Blocking glycosylation of G6PD reduces cancer cell proliferation in vitro and impairs tumor growth in vivo. 26399441 5 36 theme glucose 667:673 arg1 flux 675:678 glucose flux 667:678 glucose flux through the PPP 667:694 Glycosylation activates G6PD activity and increases glucose flux through the PPP, thereby providing precursors for nucleotide and lipid biosynthesis, and reducing equivalents for antioxidant defense. 26399441 2 37 theme PPP 265:267 arg1 Upregulation 245:256 Upregulation 245:256 Upregulation of the PPP 245:267 Upregulation of the PPP has been shown in several types of cancer. 26399441 4 38 theme β-N-acetylglucosamine 563:583 arg1 sugar 585:589 an O-linked β-N-acetylglucosamine sugar 551:589 an O-linked β-N-acetylglucosamine sugar in response to hypoxia 551:612 Here we show that glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the PPP, is dynamically modified with an O-linked β-N-acetylglucosamine sugar in response to hypoxia. 26399441 7 39 theme G6PD 936:939 arg1 glycosylation 941:953 G6PD glycosylation 936:953 G6PD glycosylation 936:953 Importantly, G6PD glycosylation is increased in human lung cancers. 26399441 1 40 theme proliferating 224:236 arg1 cells 238:242 rapidly proliferating cells 216:242 rapidly proliferating cells 216:242 The pentose phosphate pathway (PPP) plays a critical role in macromolecule biosynthesis and maintaining cellular redox homoeostasis in rapidly proliferating cells. 26399441 0 41 theme tumor 67:71 arg1 growth 73:78 tumor growth 67:78 tumor growth 67:78 O-GlcNAcylation of G6PD promotes the pentose phosphate pathway and tumor growth. 26399441 6 42 theme Blocking 815:822 arg1 glycosylation 824:836 Blocking glycosylation 815:836 Blocking glycosylation of G6PD 815:844 Blocking glycosylation of G6PD reduces cancer cell proliferation in vitro and impairs tumor growth in vivo. 26399441 4 43 from sugar 585:589 arg1 response 594:601 response 594:601 response to hypoxia 594:612 Here we show that glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the PPP, is dynamically modified with an O-linked β-N-acetylglucosamine sugar in response to hypoxia. 26399441 7 44 theme human 971:975 arg1 cancers 982:988 human lung cancers 971:988 human lung cancers 971:988 Importantly, G6PD glycosylation is increased in human lung cancers. 26399441 1 45 theme critical 125:132 arg1 role 134:137 a critical role 123:137 a critical role 123:137 The pentose phosphate pathway (PPP) plays a critical role in macromolecule biosynthesis and maintaining cellular redox homoeostasis in rapidly proliferating cells. 26362733 0 0 theme model 84:88 arg1 mice 90:93 transgenic model mice 73:93 transgenic model mice 73:93 Microglial keratan sulfate epitope elicits in central nervous tissues of transgenic model mice and patients with amyotrophic lateral sclerosis. 26362733 2 1 theme patients 450:457 arg1 use 413:415 the use 409:415 the use of SOD1(G93A) ALS model mice and patients with ALS 409:466 We therefore studied the expression of 5D4-reactive KS in amyotrophic lateral sclerosis (ALS), a motor neuron-degenerative disease, with the use of SOD1(G93A) ALS model mice and patients with ALS. 26362733 6 2 theme G93A 1189:1192 arg1 mice 1211:1214 SOD1(G93A)/GlcNAc6ST1(-/-) mice 1184:1214 SOD1(G93A)/GlcNAc6ST1(-/-) mice 1184:1214 The requirement of GlcNAc6ST1 for this synthesis was corroborated by analyzing SOD1(G93A)/GlcNAc6ST1(-/-) mice. 26362733 7 3 theme N 1267:1267 arg1 KS 1298:1299 N acteylglucosamine-6-sulfated KS 1267:1299 N acteylglucosamine-6-sulfated KS 1267:1299 These results indicate that both galactose-6- and N acteylglucosamine-6-sulfated KS elicited in the spinal cord and brainstem are associated with the degeneration of spinal and bulbar lower motor neurons in ALS pathology and may play a role in disease progression via microglial activation and proliferation. 26362733 2 4 from expression 297:306 arg1 ALS 361:363 ALS 361:363 ALS 361:363 We therefore studied the expression of 5D4-reactive KS in amyotrophic lateral sclerosis (ALS), a motor neuron-degenerative disease, with the use of SOD1(G93A) ALS model mice and patients with ALS. 26362733 2 4 from expression 297:306 arg1 sclerosis 350:358 amyotrophic lateral sclerosis 330:358 amyotrophic lateral sclerosis (ALS) 330:364 We therefore studied the expression of 5D4-reactive KS in amyotrophic lateral sclerosis (ALS), a motor neuron-degenerative disease, with the use of SOD1(G93A) ALS model mice and patients with ALS. 26362733 2 4 from expression 297:306 arg1 disease 395:401 a motor neuron-degenerative disease 367:401 a motor neuron-degenerative disease 367:401 We therefore studied the expression of 5D4-reactive KS in amyotrophic lateral sclerosis (ALS), a motor neuron-degenerative disease, with the use of SOD1(G93A) ALS model mice and patients with ALS. 26362733 1 5 theme diseases 251:258 arg1 pathogenesis 217:228 the pathogenesis 213:228 the pathogenesis of neurodegenerative diseases 213:258 The functional role of 5D4 antibody-reactive keratan sulfate (KS) in the pathogenesis of neurodegenerative diseases is unknown. 26362733 0 6 theme transgenic 73:82 arg1 mice 90:93 transgenic model mice 73:93 transgenic model mice 73:93 Microglial keratan sulfate epitope elicits in central nervous tissues of transgenic model mice and patients with amyotrophic lateral sclerosis. 26362733 3 7 theme disease 674:680 arg1 stage 686:690 disease end stage 674:690 disease end stage 674:690 Histochemical and immunoelectron microscopic characterizations showed that the 5D4-reactive KS is expressed in Mac2/galectin-3-positive activated or proliferating microglia of SOD1(G93A) ALS model mice at disease end stage and that the KS is an O-linked glycan modified with sialic acid and fucose, which was thus far shown to exist in cartilage. 26362733 7 8 theme bulbar 1394:1399 arg1 neurons 1413:1419 spinal and bulbar lower motor neurons 1383:1419 spinal and bulbar lower motor neurons in ALS pathology 1383:1436 These results indicate that both galactose-6- and N acteylglucosamine-6-sulfated KS elicited in the spinal cord and brainstem are associated with the degeneration of spinal and bulbar lower motor neurons in ALS pathology and may play a role in disease progression via microglial activation and proliferation. 26362733 1 9 from role 159:162 arg1 pathogenesis 217:228 the pathogenesis 213:228 the pathogenesis of neurodegenerative diseases 213:258 The functional role of 5D4 antibody-reactive keratan sulfate (KS) in the pathogenesis of neurodegenerative diseases is unknown. 26362733 3 10 theme Histochemical 469:481 arg1 characterizations 514:530 Histochemical and immunoelectron microscopic characterizations 469:530 Histochemical and immunoelectron microscopic characterizations 469:530 Histochemical and immunoelectron microscopic characterizations showed that the 5D4-reactive KS is expressed in Mac2/galectin-3-positive activated or proliferating microglia of SOD1(G93A) ALS model mice at disease end stage and that the KS is an O-linked glycan modified with sialic acid and fucose, which was thus far shown to exist in cartilage. 26362733 4 11 theme spinal 864:869 arg1 cord 871:874 the spinal cord 860:874 the spinal cord 860:874 Intriguingly, microglial KS was detected in the spinal cord and brainstem but not in the cerebral cortex of SOD1(G93A) mice. 26362733 3 12 theme end 682:684 arg1 stage 686:690 disease end stage 674:690 disease end stage 674:690 Histochemical and immunoelectron microscopic characterizations showed that the 5D4-reactive KS is expressed in Mac2/galectin-3-positive activated or proliferating microglia of SOD1(G93A) ALS model mice at disease end stage and that the KS is an O-linked glycan modified with sialic acid and fucose, which was thus far shown to exist in cartilage. 26362733 6 13 theme SOD1 1184:1187 arg1 mice 1211:1214 SOD1(G93A)/GlcNAc6ST1(-/-) mice 1184:1214 SOD1(G93A)/GlcNAc6ST1(-/-) mice 1184:1214 The requirement of GlcNAc6ST1 for this synthesis was corroborated by analyzing SOD1(G93A)/GlcNAc6ST1(-/-) mice. 26362733 0 14 theme mice 90:93 arg1 tissues 62:68 central nervous tissues 46:68 central nervous tissues of transgenic model mice and patients with amyotrophic lateral sclerosis 46:141 Microglial keratan sulfate epitope elicits in central nervous tissues of transgenic model mice and patients with amyotrophic lateral sclerosis. 26362733 7 15 theme ALS 1424:1426 arg1 pathology 1428:1436 ALS pathology 1424:1436 ALS pathology 1424:1436 These results indicate that both galactose-6- and N acteylglucosamine-6-sulfated KS elicited in the spinal cord and brainstem are associated with the degeneration of spinal and bulbar lower motor neurons in ALS pathology and may play a role in disease progression via microglial activation and proliferation. 26362733 4 16 theme microglial 830:839 arg1 KS 841:842 microglial KS 830:842 microglial KS 830:842 Intriguingly, microglial KS was detected in the spinal cord and brainstem but not in the cerebral cortex of SOD1(G93A) mice. 26362733 7 17 theme spinal 1383:1388 arg1 neurons 1413:1419 spinal and bulbar lower motor neurons 1383:1419 spinal and bulbar lower motor neurons in ALS pathology 1383:1436 These results indicate that both galactose-6- and N acteylglucosamine-6-sulfated KS elicited in the spinal cord and brainstem are associated with the degeneration of spinal and bulbar lower motor neurons in ALS pathology and may play a role in disease progression via microglial activation and proliferation. 26362733 7 18 from pathology 1428:1436 arg1 degeneration 1367:1378 the degeneration 1363:1378 the degeneration of spinal and bulbar lower motor neurons in ALS pathology 1363:1436 These results indicate that both galactose-6- and N acteylglucosamine-6-sulfated KS elicited in the spinal cord and brainstem are associated with the degeneration of spinal and bulbar lower motor neurons in ALS pathology and may play a role in disease progression via microglial activation and proliferation. 26362733 7 19 theme acteylglucosamine-6-sulfated 1269:1296 arg1 KS 1298:1299 N acteylglucosamine-6-sulfated KS 1267:1299 N acteylglucosamine-6-sulfated KS 1267:1299 These results indicate that both galactose-6- and N acteylglucosamine-6-sulfated KS elicited in the spinal cord and brainstem are associated with the degeneration of spinal and bulbar lower motor neurons in ALS pathology and may play a role in disease progression via microglial activation and proliferation. 26362733 3 20 theme microscopic 502:512 arg1 characterizations 514:530 Histochemical and immunoelectron microscopic characterizations 469:530 Histochemical and immunoelectron microscopic characterizations 469:530 Histochemical and immunoelectron microscopic characterizations showed that the 5D4-reactive KS is expressed in Mac2/galectin-3-positive activated or proliferating microglia of SOD1(G93A) ALS model mice at disease end stage and that the KS is an O-linked glycan modified with sialic acid and fucose, which was thus far shown to exist in cartilage. 26362733 2 21 theme motor 369:373 arg1 disease 395:401 a motor neuron-degenerative disease 367:401 a motor neuron-degenerative disease 367:401 We therefore studied the expression of 5D4-reactive KS in amyotrophic lateral sclerosis (ALS), a motor neuron-degenerative disease, with the use of SOD1(G93A) ALS model mice and patients with ALS. 26362733 2 21 theme motor 369:373 arg1 sclerosis 350:358 amyotrophic lateral sclerosis 330:358 amyotrophic lateral sclerosis (ALS) 330:364 We therefore studied the expression of 5D4-reactive KS in amyotrophic lateral sclerosis (ALS), a motor neuron-degenerative disease, with the use of SOD1(G93A) ALS model mice and patients with ALS. 26362733 1 22 theme 5D4 167:169 arg1 KS 206:207 KS 206:207 KS 206:207 The functional role of 5D4 antibody-reactive keratan sulfate (KS) in the pathogenesis of neurodegenerative diseases is unknown. 26362733 1 22 theme 5D4 167:169 arg1 sulfate 197:203 5D4 antibody-reactive keratan sulfate 167:203 5D4 antibody-reactive keratan sulfate (KS) 167:208 The functional role of 5D4 antibody-reactive keratan sulfate (KS) in the pathogenesis of neurodegenerative diseases is unknown. 26362733 0 23 theme patients 99:106 arg1 tissues 62:68 central nervous tissues 46:68 central nervous tissues of transgenic model mice and patients with amyotrophic lateral sclerosis 46:141 Microglial keratan sulfate epitope elicits in central nervous tissues of transgenic model mice and patients with amyotrophic lateral sclerosis. 26362733 4 24 theme G93A 929:932 arg1 mice 935:938 SOD1(G93A) mice 924:938 SOD1(G93A) mice 924:938 Intriguingly, microglial KS was detected in the spinal cord and brainstem but not in the cerebral cortex of SOD1(G93A) mice. 26362733 2 25 theme G93A 425:428 arg1 mice 441:444 SOD1(G93A) ALS model mice 420:444 SOD1(G93A) ALS model mice 420:444 We therefore studied the expression of 5D4-reactive KS in amyotrophic lateral sclerosis (ALS), a motor neuron-degenerative disease, with the use of SOD1(G93A) ALS model mice and patients with ALS. 26362733 1 26 theme antibody-reactive 171:187 arg1 KS 206:207 KS 206:207 KS 206:207 The functional role of 5D4 antibody-reactive keratan sulfate (KS) in the pathogenesis of neurodegenerative diseases is unknown. 26362733 1 26 theme antibody-reactive 171:187 arg1 sulfate 197:203 5D4 antibody-reactive keratan sulfate 167:203 5D4 antibody-reactive keratan sulfate (KS) 167:208 The functional role of 5D4 antibody-reactive keratan sulfate (KS) in the pathogenesis of neurodegenerative diseases is unknown. 26362733 0 27 theme keratan 11:17 arg1 sulfate 19:25 Microglial keratan sulfate 0:25 Microglial keratan sulfate epitope 0:33 Microglial keratan sulfate epitope elicits in central nervous tissues of transgenic model mice and patients with amyotrophic lateral sclerosis. 26362733 5 28 theme microglial 1033:1042 arg1 KS 1057:1058 the microglial 5D4-reactive KS 1029:1058 the microglial 5D4-reactive KS 1029:1058 We found that KSGal6ST, a galactose-6-sulfotransferase, is required for biosynthesis of the microglial 5D4-reactive KS by generating SOD1(G93A)/KSGal6ST(-/-) mice. 26362733 5 29 theme -/- 1094:1096 arg1 mice 1099:1102 SOD1(G93A)/KSGal6ST(-/-) mice 1074:1102 SOD1(G93A)/KSGal6ST(-/-) mice 1074:1102 We found that KSGal6ST, a galactose-6-sulfotransferase, is required for biosynthesis of the microglial 5D4-reactive KS by generating SOD1(G93A)/KSGal6ST(-/-) mice. 26362733 0 30 with patients 99:106 arg1 sclerosis 133:141 amyotrophic lateral sclerosis 113:141 amyotrophic lateral sclerosis 113:141 Microglial keratan sulfate epitope elicits in central nervous tissues of transgenic model mice and patients with amyotrophic lateral sclerosis. 26362733 2 31 theme KS 324:325 arg1 expression 297:306 the expression 293:306 the expression of 5D4-reactive KS in amyotrophic lateral sclerosis (ALS), a motor neuron-degenerative disease 293:401 We therefore studied the expression of 5D4-reactive KS in amyotrophic lateral sclerosis (ALS), a motor neuron-degenerative disease, with the use of SOD1(G93A) ALS model mice and patients with ALS. 26362733 1 32 theme keratan 189:195 arg1 KS 206:207 KS 206:207 KS 206:207 The functional role of 5D4 antibody-reactive keratan sulfate (KS) in the pathogenesis of neurodegenerative diseases is unknown. 26362733 1 32 theme keratan 189:195 arg1 sulfate 197:203 5D4 antibody-reactive keratan sulfate 167:203 5D4 antibody-reactive keratan sulfate (KS) 167:208 The functional role of 5D4 antibody-reactive keratan sulfate (KS) in the pathogenesis of neurodegenerative diseases is unknown. 26362733 0 33 theme Microglial 0:9 arg1 sulfate 19:25 Microglial keratan sulfate 0:25 Microglial keratan sulfate epitope 0:33 Microglial keratan sulfate epitope elicits in central nervous tissues of transgenic model mice and patients with amyotrophic lateral sclerosis. 26362733 5 34 theme /KSGal6ST 1084:1092 arg1 mice 1099:1102 SOD1(G93A)/KSGal6ST(-/-) mice 1074:1102 SOD1(G93A)/KSGal6ST(-/-) mice 1074:1102 We found that KSGal6ST, a galactose-6-sulfotransferase, is required for biosynthesis of the microglial 5D4-reactive KS by generating SOD1(G93A)/KSGal6ST(-/-) mice. 26362733 4 35 theme mice 935:938 arg1 cortex 914:919 the cerebral cortex 901:919 the cerebral cortex of SOD1(G93A) mice 901:938 Intriguingly, microglial KS was detected in the spinal cord and brainstem but not in the cerebral cortex of SOD1(G93A) mice. 26362733 2 36 theme 5D4-reactive 311:322 arg1 KS 324:325 5D4-reactive KS 311:325 5D4-reactive KS 311:325 We therefore studied the expression of 5D4-reactive KS in amyotrophic lateral sclerosis (ALS), a motor neuron-degenerative disease, with the use of SOD1(G93A) ALS model mice and patients with ALS. 26362733 1 37 theme sulfate 197:203 arg1 unknown 263:269 unknown 263:269 unknown 263:269 The functional role of 5D4 antibody-reactive keratan sulfate (KS) in the pathogenesis of neurodegenerative diseases is unknown. 26362733 1 37 theme sulfate 197:203 arg1 role 159:162 The functional role 144:162 The functional role of 5D4 antibody-reactive keratan sulfate (KS) in the pathogenesis of neurodegenerative diseases 144:258 The functional role of 5D4 antibody-reactive keratan sulfate (KS) in the pathogenesis of neurodegenerative diseases is unknown. 26362733 2 38 theme SOD1 420:423 arg1 mice 441:444 SOD1(G93A) ALS model mice 420:444 SOD1(G93A) ALS model mice 420:444 We therefore studied the expression of 5D4-reactive KS in amyotrophic lateral sclerosis (ALS), a motor neuron-degenerative disease, with the use of SOD1(G93A) ALS model mice and patients with ALS. 26362733 0 39 theme lateral 125:131 arg1 sclerosis 133:141 amyotrophic lateral sclerosis 113:141 amyotrophic lateral sclerosis 113:141 Microglial keratan sulfate epitope elicits in central nervous tissues of transgenic model mice and patients with amyotrophic lateral sclerosis. 26362733 0 40 with mice 90:93 arg1 sclerosis 133:141 amyotrophic lateral sclerosis 113:141 amyotrophic lateral sclerosis 113:141 Microglial keratan sulfate epitope elicits in central nervous tissues of transgenic model mice and patients with amyotrophic lateral sclerosis. 26362733 2 41 with patients 450:457 arg1 ALS 464:466 ALS 464:466 ALS 464:466 We therefore studied the expression of 5D4-reactive KS in amyotrophic lateral sclerosis (ALS), a motor neuron-degenerative disease, with the use of SOD1(G93A) ALS model mice and patients with ALS. 26362733 0 42 theme sulfate 19:25 arg1 epitope 27:33 Microglial keratan sulfate epitope 0:33 Microglial keratan sulfate epitope 0:33 Microglial keratan sulfate epitope elicits in central nervous tissues of transgenic model mice and patients with amyotrophic lateral sclerosis. 26362733 5 43 theme KS 1057:1058 arg1 biosynthesis 1013:1024 biosynthesis 1013:1024 biosynthesis of the microglial 5D4-reactive KS 1013:1058 We found that KSGal6ST, a galactose-6-sulfotransferase, is required for biosynthesis of the microglial 5D4-reactive KS by generating SOD1(G93A)/KSGal6ST(-/-) mice. 26362733 0 44 theme amyotrophic 113:123 arg1 sclerosis 133:141 amyotrophic lateral sclerosis 113:141 amyotrophic lateral sclerosis 113:141 Microglial keratan sulfate epitope elicits in central nervous tissues of transgenic model mice and patients with amyotrophic lateral sclerosis. 26362733 3 45 theme G93A 650:653 arg1 mice 666:669 SOD1(G93A) ALS model mice 645:669 SOD1(G93A) ALS model mice 645:669 Histochemical and immunoelectron microscopic characterizations showed that the 5D4-reactive KS is expressed in Mac2/galectin-3-positive activated or proliferating microglia of SOD1(G93A) ALS model mice at disease end stage and that the KS is an O-linked glycan modified with sialic acid and fucose, which was thus far shown to exist in cartilage. 26362733 3 46 theme 5D4-reactive 548:559 arg1 KS 561:562 the 5D4-reactive KS 544:562 the 5D4-reactive KS 544:562 Histochemical and immunoelectron microscopic characterizations showed that the 5D4-reactive KS is expressed in Mac2/galectin-3-positive activated or proliferating microglia of SOD1(G93A) ALS model mice at disease end stage and that the KS is an O-linked glycan modified with sialic acid and fucose, which was thus far shown to exist in cartilage. 26362733 2 47 theme mice 441:444 arg1 use 413:415 the use 409:415 the use of SOD1(G93A) ALS model mice and patients with ALS 409:466 We therefore studied the expression of 5D4-reactive KS in amyotrophic lateral sclerosis (ALS), a motor neuron-degenerative disease, with the use of SOD1(G93A) ALS model mice and patients with ALS. 26362733 3 48 theme O-linked 714:721 arg1 glycan 723:728 an O-linked glycan 711:728 an O-linked glycan modified with sialic acid and fucose, which was thus far shown to exist in cartilage 711:813 Histochemical and immunoelectron microscopic characterizations showed that the 5D4-reactive KS is expressed in Mac2/galectin-3-positive activated or proliferating microglia of SOD1(G93A) ALS model mice at disease end stage and that the KS is an O-linked glycan modified with sialic acid and fucose, which was thus far shown to exist in cartilage. 26362733 3 48 theme O-linked 714:721 arg1 KS 705:706 the KS 701:706 the KS 701:706 Histochemical and immunoelectron microscopic characterizations showed that the 5D4-reactive KS is expressed in Mac2/galectin-3-positive activated or proliferating microglia of SOD1(G93A) ALS model mice at disease end stage and that the KS is an O-linked glycan modified with sialic acid and fucose, which was thus far shown to exist in cartilage. 26362733 7 49 from role 1453:1456 arg1 disease progression 1461:1479 disease progression 1461:1479 disease progression 1461:1479 These results indicate that both galactose-6- and N acteylglucosamine-6-sulfated KS elicited in the spinal cord and brainstem are associated with the degeneration of spinal and bulbar lower motor neurons in ALS pathology and may play a role in disease progression via microglial activation and proliferation. 26362733 3 50 theme Mac2/galectin-3-positive 580:603 arg1 microglia 632:640 Mac2/galectin-3-positive activated or proliferating microglia 580:640 Mac2/galectin-3-positive activated or proliferating microglia of SOD1(G93A) ALS model mice 580:669 Histochemical and immunoelectron microscopic characterizations showed that the 5D4-reactive KS is expressed in Mac2/galectin-3-positive activated or proliferating microglia of SOD1(G93A) ALS model mice at disease end stage and that the KS is an O-linked glycan modified with sialic acid and fucose, which was thus far shown to exist in cartilage. 26362733 7 51 from degeneration 1367:1378 arg1 pathology 1428:1436 ALS pathology 1424:1436 ALS pathology 1424:1436 These results indicate that both galactose-6- and N acteylglucosamine-6-sulfated KS elicited in the spinal cord and brainstem are associated with the degeneration of spinal and bulbar lower motor neurons in ALS pathology and may play a role in disease progression via microglial activation and proliferation. 26362733 2 52 theme model 435:439 arg1 mice 441:444 SOD1(G93A) ALS model mice 420:444 SOD1(G93A) ALS model mice 420:444 We therefore studied the expression of 5D4-reactive KS in amyotrophic lateral sclerosis (ALS), a motor neuron-degenerative disease, with the use of SOD1(G93A) ALS model mice and patients with ALS. 26362733 5 53 theme SOD1 1074:1077 arg1 mice 1099:1102 SOD1(G93A)/KSGal6ST(-/-) mice 1074:1102 SOD1(G93A)/KSGal6ST(-/-) mice 1074:1102 We found that KSGal6ST, a galactose-6-sulfotransferase, is required for biosynthesis of the microglial 5D4-reactive KS by generating SOD1(G93A)/KSGal6ST(-/-) mice. 26362733 3 54 theme SOD1 645:648 arg1 mice 666:669 SOD1(G93A) ALS model mice 645:669 SOD1(G93A) ALS model mice 645:669 Histochemical and immunoelectron microscopic characterizations showed that the 5D4-reactive KS is expressed in Mac2/galectin-3-positive activated or proliferating microglia of SOD1(G93A) ALS model mice at disease end stage and that the KS is an O-linked glycan modified with sialic acid and fucose, which was thus far shown to exist in cartilage. 26362733 3 55 theme activated 605:613 arg1 microglia 632:640 Mac2/galectin-3-positive activated or proliferating microglia 580:640 Mac2/galectin-3-positive activated or proliferating microglia of SOD1(G93A) ALS model mice 580:669 Histochemical and immunoelectron microscopic characterizations showed that the 5D4-reactive KS is expressed in Mac2/galectin-3-positive activated or proliferating microglia of SOD1(G93A) ALS model mice at disease end stage and that the KS is an O-linked glycan modified with sialic acid and fucose, which was thus far shown to exist in cartilage. 26362733 0 56 theme nervous 54:60 arg1 tissues 62:68 central nervous tissues 46:68 central nervous tissues of transgenic model mice and patients with amyotrophic lateral sclerosis 46:141 Microglial keratan sulfate epitope elicits in central nervous tissues of transgenic model mice and patients with amyotrophic lateral sclerosis. 26362733 6 57 theme -/- 1206:1208 arg1 mice 1211:1214 SOD1(G93A)/GlcNAc6ST1(-/-) mice 1184:1214 SOD1(G93A)/GlcNAc6ST1(-/-) mice 1184:1214 The requirement of GlcNAc6ST1 for this synthesis was corroborated by analyzing SOD1(G93A)/GlcNAc6ST1(-/-) mice. 26362733 4 58 theme cerebral 905:912 arg1 cortex 914:919 the cerebral cortex 901:919 the cerebral cortex of SOD1(G93A) mice 901:938 Intriguingly, microglial KS was detected in the spinal cord and brainstem but not in the cerebral cortex of SOD1(G93A) mice. 26362733 6 59 theme GlcNAc6ST1 1124:1133 arg1 requirement 1109:1119 The requirement 1105:1119 The requirement of GlcNAc6ST1 for this synthesis 1105:1152 The requirement of GlcNAc6ST1 for this synthesis was corroborated by analyzing SOD1(G93A)/GlcNAc6ST1(-/-) mice. 26362733 0 60 theme central 46:52 arg1 tissues 62:68 central nervous tissues 46:68 central nervous tissues of transgenic model mice and patients with amyotrophic lateral sclerosis 46:141 Microglial keratan sulfate epitope elicits in central nervous tissues of transgenic model mice and patients with amyotrophic lateral sclerosis. 26362733 5 61 theme G93A 1079:1082 arg1 mice 1099:1102 SOD1(G93A)/KSGal6ST(-/-) mice 1074:1102 SOD1(G93A)/KSGal6ST(-/-) mice 1074:1102 We found that KSGal6ST, a galactose-6-sulfotransferase, is required for biosynthesis of the microglial 5D4-reactive KS by generating SOD1(G93A)/KSGal6ST(-/-) mice. 26362733 5 62 theme 5D4-reactive 1044:1055 arg1 KS 1057:1058 the microglial 5D4-reactive KS 1029:1058 the microglial 5D4-reactive KS 1029:1058 We found that KSGal6ST, a galactose-6-sulfotransferase, is required for biosynthesis of the microglial 5D4-reactive KS by generating SOD1(G93A)/KSGal6ST(-/-) mice. 26362733 3 63 theme mice 666:669 arg1 microglia 632:640 Mac2/galectin-3-positive activated or proliferating microglia 580:640 Mac2/galectin-3-positive activated or proliferating microglia of SOD1(G93A) ALS model mice 580:669 Histochemical and immunoelectron microscopic characterizations showed that the 5D4-reactive KS is expressed in Mac2/galectin-3-positive activated or proliferating microglia of SOD1(G93A) ALS model mice at disease end stage and that the KS is an O-linked glycan modified with sialic acid and fucose, which was thus far shown to exist in cartilage. 26362733 7 64 from neurons 1413:1419 arg1 pathology 1428:1436 ALS pathology 1424:1436 ALS pathology 1424:1436 These results indicate that both galactose-6- and N acteylglucosamine-6-sulfated KS elicited in the spinal cord and brainstem are associated with the degeneration of spinal and bulbar lower motor neurons in ALS pathology and may play a role in disease progression via microglial activation and proliferation. 26362733 2 65 theme lateral 342:348 arg1 ALS 361:363 ALS 361:363 ALS 361:363 We therefore studied the expression of 5D4-reactive KS in amyotrophic lateral sclerosis (ALS), a motor neuron-degenerative disease, with the use of SOD1(G93A) ALS model mice and patients with ALS. 26362733 2 65 theme lateral 342:348 arg1 sclerosis 350:358 amyotrophic lateral sclerosis 330:358 amyotrophic lateral sclerosis (ALS) 330:364 We therefore studied the expression of 5D4-reactive KS in amyotrophic lateral sclerosis (ALS), a motor neuron-degenerative disease, with the use of SOD1(G93A) ALS model mice and patients with ALS. 26362733 2 65 theme lateral 342:348 arg1 disease 395:401 a motor neuron-degenerative disease 367:401 a motor neuron-degenerative disease 367:401 We therefore studied the expression of 5D4-reactive KS in amyotrophic lateral sclerosis (ALS), a motor neuron-degenerative disease, with the use of SOD1(G93A) ALS model mice and patients with ALS. 26362733 3 66 theme sialic 744:749 arg1 acid 751:754 sialic acid 744:754 sialic acid 744:754 Histochemical and immunoelectron microscopic characterizations showed that the 5D4-reactive KS is expressed in Mac2/galectin-3-positive activated or proliferating microglia of SOD1(G93A) ALS model mice at disease end stage and that the KS is an O-linked glycan modified with sialic acid and fucose, which was thus far shown to exist in cartilage. 26362733 6 67 theme /GlcNAc6ST1 1194:1204 arg1 mice 1211:1214 SOD1(G93A)/GlcNAc6ST1(-/-) mice 1184:1214 SOD1(G93A)/GlcNAc6ST1(-/-) mice 1184:1214 The requirement of GlcNAc6ST1 for this synthesis was corroborated by analyzing SOD1(G93A)/GlcNAc6ST1(-/-) mice. 26362733 7 68 theme neurons 1413:1419 arg1 degeneration 1367:1378 the degeneration 1363:1378 the degeneration of spinal and bulbar lower motor neurons in ALS pathology 1363:1436 These results indicate that both galactose-6- and N acteylglucosamine-6-sulfated KS elicited in the spinal cord and brainstem are associated with the degeneration of spinal and bulbar lower motor neurons in ALS pathology and may play a role in disease progression via microglial activation and proliferation. 26362733 7 69 theme motor 1407:1411 arg1 neurons 1413:1419 spinal and bulbar lower motor neurons 1383:1419 spinal and bulbar lower motor neurons in ALS pathology 1383:1436 These results indicate that both galactose-6- and N acteylglucosamine-6-sulfated KS elicited in the spinal cord and brainstem are associated with the degeneration of spinal and bulbar lower motor neurons in ALS pathology and may play a role in disease progression via microglial activation and proliferation. 26362733 7 70 theme spinal 1317:1322 arg1 cord 1324:1327 the spinal cord 1313:1327 the spinal cord 1313:1327 These results indicate that both galactose-6- and N acteylglucosamine-6-sulfated KS elicited in the spinal cord and brainstem are associated with the degeneration of spinal and bulbar lower motor neurons in ALS pathology and may play a role in disease progression via microglial activation and proliferation. 26362733 2 71 theme amyotrophic 330:340 arg1 ALS 361:363 ALS 361:363 ALS 361:363 We therefore studied the expression of 5D4-reactive KS in amyotrophic lateral sclerosis (ALS), a motor neuron-degenerative disease, with the use of SOD1(G93A) ALS model mice and patients with ALS. 26362733 2 71 theme amyotrophic 330:340 arg1 sclerosis 350:358 amyotrophic lateral sclerosis 330:358 amyotrophic lateral sclerosis (ALS) 330:364 We therefore studied the expression of 5D4-reactive KS in amyotrophic lateral sclerosis (ALS), a motor neuron-degenerative disease, with the use of SOD1(G93A) ALS model mice and patients with ALS. 26362733 2 71 theme amyotrophic 330:340 arg1 disease 395:401 a motor neuron-degenerative disease 367:401 a motor neuron-degenerative disease 367:401 We therefore studied the expression of 5D4-reactive KS in amyotrophic lateral sclerosis (ALS), a motor neuron-degenerative disease, with the use of SOD1(G93A) ALS model mice and patients with ALS. 26362733 7 72 theme microglial 1485:1494 arg1 activation 1496:1505 microglial activation 1485:1505 microglial activation 1485:1505 These results indicate that both galactose-6- and N acteylglucosamine-6-sulfated KS elicited in the spinal cord and brainstem are associated with the degeneration of spinal and bulbar lower motor neurons in ALS pathology and may play a role in disease progression via microglial activation and proliferation. 26362733 3 73 theme ALS 656:658 arg1 mice 666:669 SOD1(G93A) ALS model mice 645:669 SOD1(G93A) ALS model mice 645:669 Histochemical and immunoelectron microscopic characterizations showed that the 5D4-reactive KS is expressed in Mac2/galectin-3-positive activated or proliferating microglia of SOD1(G93A) ALS model mice at disease end stage and that the KS is an O-linked glycan modified with sialic acid and fucose, which was thus far shown to exist in cartilage. 26362733 4 74 located detected 848:855 arg2 KS 841:842 microglial KS 830:842 microglial KS 830:842 Intriguingly, microglial KS was detected in the spinal cord and brainstem but not in the cerebral cortex of SOD1(G93A) mice. 26362733 4 74 located detected 848:855 arg1 cord 871:874 the spinal cord 860:874 the spinal cord 860:874 Intriguingly, microglial KS was detected in the spinal cord and brainstem but not in the cerebral cortex of SOD1(G93A) mice. 26362733 3 75 theme model 660:664 arg1 mice 666:669 SOD1(G93A) ALS model mice 645:669 SOD1(G93A) ALS model mice 645:669 Histochemical and immunoelectron microscopic characterizations showed that the 5D4-reactive KS is expressed in Mac2/galectin-3-positive activated or proliferating microglia of SOD1(G93A) ALS model mice at disease end stage and that the KS is an O-linked glycan modified with sialic acid and fucose, which was thus far shown to exist in cartilage. 26362733 3 76 link O-linked 714:721 arg1 glycan 723:728 an O-linked glycan 711:728 an O-linked glycan modified with sialic acid and fucose, which was thus far shown to exist in cartilage 711:813 Histochemical and immunoelectron microscopic characterizations showed that the 5D4-reactive KS is expressed in Mac2/galectin-3-positive activated or proliferating microglia of SOD1(G93A) ALS model mice at disease end stage and that the KS is an O-linked glycan modified with sialic acid and fucose, which was thus far shown to exist in cartilage. 26362733 3 76 link O-linked 714:721 arg1 KS 705:706 the KS 701:706 the KS 701:706 Histochemical and immunoelectron microscopic characterizations showed that the 5D4-reactive KS is expressed in Mac2/galectin-3-positive activated or proliferating microglia of SOD1(G93A) ALS model mice at disease end stage and that the KS is an O-linked glycan modified with sialic acid and fucose, which was thus far shown to exist in cartilage. 26362733 2 77 theme neuron-degenerative 375:393 arg1 disease 395:401 a motor neuron-degenerative disease 367:401 a motor neuron-degenerative disease 367:401 We therefore studied the expression of 5D4-reactive KS in amyotrophic lateral sclerosis (ALS), a motor neuron-degenerative disease, with the use of SOD1(G93A) ALS model mice and patients with ALS. 26362733 2 77 theme neuron-degenerative 375:393 arg1 sclerosis 350:358 amyotrophic lateral sclerosis 330:358 amyotrophic lateral sclerosis (ALS) 330:364 We therefore studied the expression of 5D4-reactive KS in amyotrophic lateral sclerosis (ALS), a motor neuron-degenerative disease, with the use of SOD1(G93A) ALS model mice and patients with ALS. 26362733 2 78 theme ALS 431:433 arg1 mice 441:444 SOD1(G93A) ALS model mice 420:444 SOD1(G93A) ALS model mice 420:444 We therefore studied the expression of 5D4-reactive KS in amyotrophic lateral sclerosis (ALS), a motor neuron-degenerative disease, with the use of SOD1(G93A) ALS model mice and patients with ALS. 26362733 4 79 theme SOD1 924:927 arg1 mice 935:938 SOD1(G93A) mice 924:938 SOD1(G93A) mice 924:938 Intriguingly, microglial KS was detected in the spinal cord and brainstem but not in the cerebral cortex of SOD1(G93A) mice. 26362733 3 80 theme proliferating 618:630 arg1 microglia 632:640 Mac2/galectin-3-positive activated or proliferating microglia 580:640 Mac2/galectin-3-positive activated or proliferating microglia of SOD1(G93A) ALS model mice 580:669 Histochemical and immunoelectron microscopic characterizations showed that the 5D4-reactive KS is expressed in Mac2/galectin-3-positive activated or proliferating microglia of SOD1(G93A) ALS model mice at disease end stage and that the KS is an O-linked glycan modified with sialic acid and fucose, which was thus far shown to exist in cartilage. 26362733 2 81 with mice 441:444 arg1 ALS 464:466 ALS 464:466 ALS 464:466 We therefore studied the expression of 5D4-reactive KS in amyotrophic lateral sclerosis (ALS), a motor neuron-degenerative disease, with the use of SOD1(G93A) ALS model mice and patients with ALS. 26362733 1 82 theme functional 148:157 arg1 unknown 263:269 unknown 263:269 unknown 263:269 The functional role of 5D4 antibody-reactive keratan sulfate (KS) in the pathogenesis of neurodegenerative diseases is unknown. 26362733 1 82 theme functional 148:157 arg1 role 159:162 The functional role 144:162 The functional role of 5D4 antibody-reactive keratan sulfate (KS) in the pathogenesis of neurodegenerative diseases 144:258 The functional role of 5D4 antibody-reactive keratan sulfate (KS) in the pathogenesis of neurodegenerative diseases is unknown. 26362733 1 83 theme neurodegenerative 233:249 arg1 diseases 251:258 neurodegenerative diseases 233:258 neurodegenerative diseases 233:258 The functional role of 5D4 antibody-reactive keratan sulfate (KS) in the pathogenesis of neurodegenerative diseases is unknown. 26012782 6 0 theme cytometric 1047:1056 arg1 analysis 1058:1065 A flow cytometric analysis 1040:1065 A flow cytometric analysis 1040:1065 A flow cytometric analysis showed that fetal and young adult neurospheres were divided into INCA mAb(-) CD133 polyclonal antibody (pAb)(-), INCA mAb(+) CD133 pAb(-), and INCA mAb(+) CD133 pAb(+) cell populations based on the reactivity against INCA mAb and CD133 pAb. 26012782 9 1 theme useful 1617:1622 arg1 mAb 1603:1605 INCA mAb 1598:1605 INCA mAb 1598:1605 INCA mAb will be a useful immunological probe in the study of NSCs. 26012782 9 1 theme useful 1617:1622 arg1 probe 1638:1642 a useful immunological probe 1615:1642 a useful immunological probe 1615:1642 INCA mAb will be a useful immunological probe in the study of NSCs. 26012782 3 2 theme INCA 453:456 arg1 mAb 458:460 INCA mAb 453:460 INCA mAb 453:460 INCA mAb specifically reacted with neuroepithelial cells in fetal cerebrums and ependymal cells in adult cerebrums. 26012782 6 3 theme INCA 1284:1287 arg1 mAb 1289:1291 INCA mAb 1284:1291 INCA mAb 1284:1291 A flow cytometric analysis showed that fetal and young adult neurospheres were divided into INCA mAb(-) CD133 polyclonal antibody (pAb)(-), INCA mAb(+) CD133 pAb(-), and INCA mAb(+) CD133 pAb(+) cell populations based on the reactivity against INCA mAb and CD133 pAb. 26012782 4 4 gly glycoproteins 623:635 arg1 molecules 585:593 The recognition molecules 569:593 The recognition molecules 569:593 The recognition molecules were O-linked 40 and 42 kDa glycoproteins on the cell membrane surface (gp40 INCA and gp42 INCA). 26012782 4 4 gly glycoproteins 623:635 arg1 glycoproteins 623:635 O-linked 40 and 42 kDa glycoproteins 600:635 O-linked 40 and 42 kDa glycoproteins 600:635 The recognition molecules were O-linked 40 and 42 kDa glycoproteins on the cell membrane surface (gp40 INCA and gp42 INCA). 26012782 4 5 from glycoproteins 623:635 arg1 surface 658:664 the cell membrane surface 640:664 the cell membrane surface (gp40 INCA and gp42 INCA) 640:690 The recognition molecules were O-linked 40 and 42 kDa glycoproteins on the cell membrane surface (gp40 INCA and gp42 INCA). 26012782 6 6 theme INCA 1132:1135 arg1 mAb 1137:1139 INCA mAb 1132:1139 INCA mAb 1132:1139 A flow cytometric analysis showed that fetal and young adult neurospheres were divided into INCA mAb(-) CD133 polyclonal antibody (pAb)(-), INCA mAb(+) CD133 pAb(-), and INCA mAb(+) CD133 pAb(+) cell populations based on the reactivity against INCA mAb and CD133 pAb. 26012782 4 7 theme 42 616:617 arg1 molecules 585:593 The recognition molecules 569:593 The recognition molecules 569:593 The recognition molecules were O-linked 40 and 42 kDa glycoproteins on the cell membrane surface (gp40 INCA and gp42 INCA). 26012782 4 7 theme 42 616:617 arg1 glycoproteins 623:635 O-linked 40 and 42 kDa glycoproteins 600:635 O-linked 40 and 42 kDa glycoproteins 600:635 The recognition molecules were O-linked 40 and 42 kDa glycoproteins on the cell membrane surface (gp40 INCA and gp42 INCA). 26012782 1 8 theme surface 172:178 arg1 antigens 180:187 few useful cell membrane surface antigens 147:187 few useful cell membrane surface antigens suitable for identification and isolation of neural stem cells (NSCs) 147:257 There are still few useful cell membrane surface antigens suitable for identification and isolation of neural stem cells (NSCs). 26012782 8 9 theme INCA 1529:1532 arg1 mAb 1534:1536 INCA mAb 1529:1536 INCA mAb 1529:1536 Neurospheres formed by clonal expansion of INCA mAb(+) CD133 pAb(+) cells gave rise to neurons and glial cells. 26012782 1 10 theme suitable 189:196 arg1 antigens 180:187 few useful cell membrane surface antigens 147:187 few useful cell membrane surface antigens suitable for identification and isolation of neural stem cells (NSCs) 147:257 There are still few useful cell membrane surface antigens suitable for identification and isolation of neural stem cells (NSCs). 26012782 8 11 theme pAb 1547:1549 arg1 cells 1554:1558 INCA mAb(+) CD133 pAb(+) cells 1529:1558 INCA mAb(+) CD133 pAb(+) cells 1529:1558 Neurospheres formed by clonal expansion of INCA mAb(+) CD133 pAb(+) cells gave rise to neurons and glial cells. 26012782 5 12 theme ependymal 1023:1031 arg1 cells 1033:1037 ependymal cells 1023:1037 ependymal cells 1023:1037 Based on expression pattern analysis of the recognition molecules in developing cerebrums, it was concluded that gp42 INCA was a stage-specific antigen expressed on undifferentiated neuroepithelial cells, while gp40 INCA was a cell lineage-specific antigen expressed at the stages of differentiation from neuroepithelial cells to ependymal cells. 26012782 3 13 theme fetal 513:517 arg1 cerebrums 519:527 fetal cerebrums 513:527 fetal cerebrums 513:527 INCA mAb specifically reacted with neuroepithelial cells in fetal cerebrums and ependymal cells in adult cerebrums. 26012782 0 14 from Characteristics 76:90 arg1 Neurospheres 117:128 Neurospheres 117:128 Neurospheres 117:128 A Novel Monoclonal Antibody Against Neuroepithelial and Ependymal Cells and Characteristics of Its Positive Cells in Neurospheres. 26012782 4 15 theme 40 609:610 arg1 kDa 619:621 kDa 619:621 kDa 619:621 The recognition molecules were O-linked 40 and 42 kDa glycoproteins on the cell membrane surface (gp40 INCA and gp42 INCA). 26012782 3 16 theme adult 552:556 arg1 cerebrums 558:566 adult cerebrums 552:566 adult cerebrums 552:566 INCA mAb specifically reacted with neuroepithelial cells in fetal cerebrums and ependymal cells in adult cerebrums. 26012782 5 17 from cerebrums 773:781 arg1 analysis 721:728 expression pattern analysis 702:728 expression pattern analysis of the recognition molecules in developing cerebrums 702:781 Based on expression pattern analysis of the recognition molecules in developing cerebrums, it was concluded that gp42 INCA was a stage-specific antigen expressed on undifferentiated neuroepithelial cells, while gp40 INCA was a cell lineage-specific antigen expressed at the stages of differentiation from neuroepithelial cells to ependymal cells. 26012782 0 18 from Cells 108:112 arg1 Neurospheres 117:128 Neurospheres 117:128 Neurospheres 117:128 A Novel Monoclonal Antibody Against Neuroepithelial and Ependymal Cells and Characteristics of Its Positive Cells in Neurospheres. 26012782 6 19 theme polyclonal 1150:1159 arg1 pAb 1171:1173 CD133 polyclonal antibody (pAb)(-), INCA mAb(+) CD133 pAb(-), 1144:1204 pAb 1171:1173 A flow cytometric analysis showed that fetal and young adult neurospheres were divided into INCA mAb(-) CD133 polyclonal antibody (pAb)(-), INCA mAb(+) CD133 pAb(-), and INCA mAb(+) CD133 pAb(+) cell populations based on the reactivity against INCA mAb and CD133 pAb. 26012782 3 20 theme neuroepithelial 488:502 arg1 cells 504:508 neuroepithelial cells 488:508 neuroepithelial cells in fetal cerebrums and ependymal cells in adult cerebrums 488:566 INCA mAb specifically reacted with neuroepithelial cells in fetal cerebrums and ependymal cells in adult cerebrums. 26012782 5 21 theme neuroepithelial 875:889 arg1 cells 891:895 undifferentiated neuroepithelial cells 858:895 undifferentiated neuroepithelial cells 858:895 Based on expression pattern analysis of the recognition molecules in developing cerebrums, it was concluded that gp42 INCA was a stage-specific antigen expressed on undifferentiated neuroepithelial cells, while gp40 INCA was a cell lineage-specific antigen expressed at the stages of differentiation from neuroepithelial cells to ependymal cells. 26012782 7 22 theme CD133 1395:1399 arg1 pAb 1401:1403 CD133 pAb 1395:1403 CD133 pAb 1395:1403 The proportion of cells having the neurosphere formation capability in the INCA mAb(+) CD133 pAb(+) cell population was significantly larger than that of undivided neurospheres. 26012782 2 23 theme cerebrum 443:450 arg1 ventricle 422:430 a lateral ventricle 412:430 a lateral ventricle of a fetal cerebrum 412:450 We generated a novel monoclonal antibody (mAb), designated as mAb against immature neural cell antigens (INCA mAb), which reacted with the areas around a lateral ventricle of a fetal cerebrum. 26012782 6 24 theme pAb 1228:1230 arg1 populations 1240:1250 INCA mAb(-) CD133 polyclonal antibody (pAb)(-), INCA mAb(+) CD133 pAb(-), and INCA mAb(+) CD133 pAb(+) cell populations 1132:1250 INCA mAb(-) CD133 polyclonal antibody (pAb)(-), INCA mAb(+) CD133 pAb(-), and INCA mAb(+) CD133 pAb(+) cell populations based on the reactivity against INCA mAb and CD133 pAb 1132:1305 A flow cytometric analysis showed that fetal and young adult neurospheres were divided into INCA mAb(-) CD133 polyclonal antibody (pAb)(-), INCA mAb(+) CD133 pAb(-), and INCA mAb(+) CD133 pAb(+) cell populations based on the reactivity against INCA mAb and CD133 pAb. 26012782 5 25 theme developing 762:771 arg1 cerebrums 773:781 developing cerebrums 762:781 developing cerebrums 762:781 Based on expression pattern analysis of the recognition molecules in developing cerebrums, it was concluded that gp42 INCA was a stage-specific antigen expressed on undifferentiated neuroepithelial cells, while gp40 INCA was a cell lineage-specific antigen expressed at the stages of differentiation from neuroepithelial cells to ependymal cells. 26012782 8 26 theme cells 1554:1558 arg1 expansion 1516:1524 clonal expansion 1509:1524 clonal expansion of INCA mAb(+) CD133 pAb(+) cells 1509:1558 Neurospheres formed by clonal expansion of INCA mAb(+) CD133 pAb(+) cells gave rise to neurons and glial cells. 26012782 1 27 theme few 147:149 arg1 antigens 180:187 few useful cell membrane surface antigens 147:187 few useful cell membrane surface antigens suitable for identification and isolation of neural stem cells (NSCs) 147:257 There are still few useful cell membrane surface antigens suitable for identification and isolation of neural stem cells (NSCs). 26012782 4 28 theme membrane 649:656 arg1 surface 658:664 the cell membrane surface 640:664 the cell membrane surface (gp40 INCA and gp42 INCA) 640:690 The recognition molecules were O-linked 40 and 42 kDa glycoproteins on the cell membrane surface (gp40 INCA and gp42 INCA). 26012782 5 29 theme expression 702:711 arg1 analysis 721:728 expression pattern analysis 702:728 expression pattern analysis of the recognition molecules in developing cerebrums 702:781 Based on expression pattern analysis of the recognition molecules in developing cerebrums, it was concluded that gp42 INCA was a stage-specific antigen expressed on undifferentiated neuroepithelial cells, while gp40 INCA was a cell lineage-specific antigen expressed at the stages of differentiation from neuroepithelial cells to ependymal cells. 26012782 1 30 theme cell 158:161 arg1 antigens 180:187 few useful cell membrane surface antigens 147:187 few useful cell membrane surface antigens suitable for identification and isolation of neural stem cells (NSCs) 147:257 There are still few useful cell membrane surface antigens suitable for identification and isolation of neural stem cells (NSCs). 26012782 6 31 dep pAb 1171:1173 arg1 pAb 1198:1200 CD133 pAb 1192:1200 CD133 pAb 1192:1200 A flow cytometric analysis showed that fetal and young adult neurospheres were divided into INCA mAb(-) CD133 polyclonal antibody (pAb)(-), INCA mAb(+) CD133 pAb(-), and INCA mAb(+) CD133 pAb(+) cell populations based on the reactivity against INCA mAb and CD133 pAb. 26012782 6 31 dep pAb 1171:1173 arg1 mAb 1185:1187 INCA mAb 1180:1187 INCA mAb 1180:1187 A flow cytometric analysis showed that fetal and young adult neurospheres were divided into INCA mAb(-) CD133 polyclonal antibody (pAb)(-), INCA mAb(+) CD133 pAb(-), and INCA mAb(+) CD133 pAb(+) cell populations based on the reactivity against INCA mAb and CD133 pAb. 26012782 6 31 dep pAb 1171:1173 arg1 - 1176:1176 - 1176:1176 - 1176:1176 A flow cytometric analysis showed that fetal and young adult neurospheres were divided into INCA mAb(-) CD133 polyclonal antibody (pAb)(-), INCA mAb(+) CD133 pAb(-), and INCA mAb(+) CD133 pAb(+) cell populations based on the reactivity against INCA mAb and CD133 pAb. 26012782 7 32 theme mAb 1388:1390 arg1 population 1413:1422 the INCA mAb(+) CD133 pAb(+) cell population 1379:1422 the INCA mAb(+) CD133 pAb(+) cell population 1379:1422 The proportion of cells having the neurosphere formation capability in the INCA mAb(+) CD133 pAb(+) cell population was significantly larger than that of undivided neurospheres. 26012782 6 33 theme CD133 1144:1148 arg1 pAb 1171:1173 CD133 polyclonal antibody (pAb)(-), INCA mAb(+) CD133 pAb(-), 1144:1204 pAb 1171:1173 A flow cytometric analysis showed that fetal and young adult neurospheres were divided into INCA mAb(-) CD133 polyclonal antibody (pAb)(-), INCA mAb(+) CD133 pAb(-), and INCA mAb(+) CD133 pAb(+) cell populations based on the reactivity against INCA mAb and CD133 pAb. 26012782 4 34 dep surface 658:664 arg1 INCA 686:689 gp42 INCA 681:689 gp42 INCA 681:689 The recognition molecules were O-linked 40 and 42 kDa glycoproteins on the cell membrane surface (gp40 INCA and gp42 INCA). 26012782 4 34 dep surface 658:664 arg1 INCA 672:675 gp40 INCA 667:675 gp40 INCA 667:675 The recognition molecules were O-linked 40 and 42 kDa glycoproteins on the cell membrane surface (gp40 INCA and gp42 INCA). 26012782 6 35 theme mAb 1137:1139 arg1 populations 1240:1250 INCA mAb(-) CD133 polyclonal antibody (pAb)(-), INCA mAb(+) CD133 pAb(-), and INCA mAb(+) CD133 pAb(+) cell populations 1132:1250 INCA mAb(-) CD133 polyclonal antibody (pAb)(-), INCA mAb(+) CD133 pAb(-), and INCA mAb(+) CD133 pAb(+) cell populations based on the reactivity against INCA mAb and CD133 pAb 1132:1305 A flow cytometric analysis showed that fetal and young adult neurospheres were divided into INCA mAb(-) CD133 polyclonal antibody (pAb)(-), INCA mAb(+) CD133 pAb(-), and INCA mAb(+) CD133 pAb(+) cell populations based on the reactivity against INCA mAb and CD133 pAb. 26012782 2 36 theme INCA 365:368 arg1 antigens 355:362 immature neural cell antigens 334:362 immature neural cell antigens (INCA mAb) 334:373 We generated a novel monoclonal antibody (mAb), designated as mAb against immature neural cell antigens (INCA mAb), which reacted with the areas around a lateral ventricle of a fetal cerebrum. 26012782 2 36 theme INCA 365:368 arg1 mAb 370:372 INCA mAb 365:372 INCA mAb 365:372 We generated a novel monoclonal antibody (mAb), designated as mAb against immature neural cell antigens (INCA mAb), which reacted with the areas around a lateral ventricle of a fetal cerebrum. 26012782 0 37 theme Cells 108:112 arg1 Characteristics 76:90 Characteristics 76:90 Characteristics of Its Positive Cells in Neurospheres 76:128 A Novel Monoclonal Antibody Against Neuroepithelial and Ependymal Cells and Characteristics of Its Positive Cells in Neurospheres. 26012782 0 37 theme Cells 108:112 arg1 Antibody 19:26 A Novel Monoclonal Antibody 0:26 A Novel Monoclonal Antibody Against Neuroepithelial and Ependymal Cells 0:70 A Novel Monoclonal Antibody Against Neuroepithelial and Ependymal Cells and Characteristics of Its Positive Cells in Neurospheres. 26012782 0 38 theme Neuroepithelial 36:50 arg1 Cells 66:70 Neuroepithelial and Ependymal Cells 36:70 Cells 66:70 A Novel Monoclonal Antibody Against Neuroepithelial and Ependymal Cells and Characteristics of Its Positive Cells in Neurospheres. 26012782 8 39 theme glial 1585:1589 arg1 cells 1591:1595 glial cells 1585:1595 glial cells 1585:1595 Neurospheres formed by clonal expansion of INCA mAb(+) CD133 pAb(+) cells gave rise to neurons and glial cells. 26012782 5 40 theme cell 920:923 arg1 antigen 942:948 a cell lineage-specific antigen 918:948 a cell lineage-specific antigen expressed at the stages of differentiation from neuroepithelial cells to ependymal cells 918:1037 Based on expression pattern analysis of the recognition molecules in developing cerebrums, it was concluded that gp42 INCA was a stage-specific antigen expressed on undifferentiated neuroepithelial cells, while gp40 INCA was a cell lineage-specific antigen expressed at the stages of differentiation from neuroepithelial cells to ependymal cells. 26012782 5 40 theme cell 920:923 arg1 INCA 909:912 gp40 INCA 904:912 gp40 INCA 904:912 Based on expression pattern analysis of the recognition molecules in developing cerebrums, it was concluded that gp42 INCA was a stage-specific antigen expressed on undifferentiated neuroepithelial cells, while gp40 INCA was a cell lineage-specific antigen expressed at the stages of differentiation from neuroepithelial cells to ependymal cells. 26012782 7 41 theme undivided 1462:1470 arg1 neurospheres 1472:1483 undivided neurospheres 1462:1483 undivided neurospheres 1462:1483 The proportion of cells having the neurosphere formation capability in the INCA mAb(+) CD133 pAb(+) cell population was significantly larger than that of undivided neurospheres. 26012782 4 42 theme gp42 681:684 arg1 INCA 686:689 gp42 INCA 681:689 gp42 INCA 681:689 The recognition molecules were O-linked 40 and 42 kDa glycoproteins on the cell membrane surface (gp40 INCA and gp42 INCA). 26012782 5 43 theme molecules 749:757 arg1 analysis 721:728 expression pattern analysis 702:728 expression pattern analysis of the recognition molecules in developing cerebrums 702:781 Based on expression pattern analysis of the recognition molecules in developing cerebrums, it was concluded that gp42 INCA was a stage-specific antigen expressed on undifferentiated neuroepithelial cells, while gp40 INCA was a cell lineage-specific antigen expressed at the stages of differentiation from neuroepithelial cells to ependymal cells. 26012782 3 44 from cells 543:547 arg1 cerebrums 558:566 adult cerebrums 552:566 adult cerebrums 552:566 INCA mAb specifically reacted with neuroepithelial cells in fetal cerebrums and ependymal cells in adult cerebrums. 26012782 0 45 theme Monoclonal 8:17 arg1 Antibody 19:26 A Novel Monoclonal Antibody 0:26 A Novel Monoclonal Antibody Against Neuroepithelial and Ependymal Cells 0:70 A Novel Monoclonal Antibody Against Neuroepithelial and Ependymal Cells and Characteristics of Its Positive Cells in Neurospheres. 26012782 7 46 theme formation 1355:1363 arg1 capability 1365:1374 the neurosphere formation capability 1339:1374 the neurosphere formation capability in the INCA mAb(+) CD133 pAb(+) cell population 1339:1422 The proportion of cells having the neurosphere formation capability in the INCA mAb(+) CD133 pAb(+) cell population was significantly larger than that of undivided neurospheres. 26012782 5 47 theme gp40 904:907 arg1 antigen 942:948 a cell lineage-specific antigen 918:948 a cell lineage-specific antigen expressed at the stages of differentiation from neuroepithelial cells to ependymal cells 918:1037 Based on expression pattern analysis of the recognition molecules in developing cerebrums, it was concluded that gp42 INCA was a stage-specific antigen expressed on undifferentiated neuroepithelial cells, while gp40 INCA was a cell lineage-specific antigen expressed at the stages of differentiation from neuroepithelial cells to ependymal cells. 26012782 5 47 theme gp40 904:907 arg1 INCA 909:912 gp40 INCA 904:912 gp40 INCA 904:912 Based on expression pattern analysis of the recognition molecules in developing cerebrums, it was concluded that gp42 INCA was a stage-specific antigen expressed on undifferentiated neuroepithelial cells, while gp40 INCA was a cell lineage-specific antigen expressed at the stages of differentiation from neuroepithelial cells to ependymal cells. 26012782 6 48 theme cell 1235:1238 arg1 populations 1240:1250 INCA mAb(-) CD133 polyclonal antibody (pAb)(-), INCA mAb(+) CD133 pAb(-), and INCA mAb(+) CD133 pAb(+) cell populations 1132:1250 INCA mAb(-) CD133 polyclonal antibody (pAb)(-), INCA mAb(+) CD133 pAb(-), and INCA mAb(+) CD133 pAb(+) cell populations based on the reactivity against INCA mAb and CD133 pAb 1132:1305 A flow cytometric analysis showed that fetal and young adult neurospheres were divided into INCA mAb(-) CD133 polyclonal antibody (pAb)(-), INCA mAb(+) CD133 pAb(-), and INCA mAb(+) CD133 pAb(+) cell populations based on the reactivity against INCA mAb and CD133 pAb. 26012782 7 49 theme cells 1326:1330 arg1 proportion 1312:1321 The proportion 1308:1321 The proportion of cells having the neurosphere formation capability in the INCA mAb(+) CD133 pAb(+) cell population 1308:1422 The proportion of cells having the neurosphere formation capability in the INCA mAb(+) CD133 pAb(+) cell population was significantly larger than that of undivided neurospheres. 26012782 7 49 theme cells 1326:1330 arg1 larger 1442:1447 larger 1442:1447 larger 1442:1447 The proportion of cells having the neurosphere formation capability in the INCA mAb(+) CD133 pAb(+) cell population was significantly larger than that of undivided neurospheres. 26012782 5 50 theme differentiation 977:991 arg1 stages 967:972 the stages 963:972 the stages of differentiation from neuroepithelial cells to ependymal cells 963:1037 Based on expression pattern analysis of the recognition molecules in developing cerebrums, it was concluded that gp42 INCA was a stage-specific antigen expressed on undifferentiated neuroepithelial cells, while gp40 INCA was a cell lineage-specific antigen expressed at the stages of differentiation from neuroepithelial cells to ependymal cells. 26012782 9 51 theme INCA 1598:1601 arg1 mAb 1603:1605 INCA mAb 1598:1605 INCA mAb 1598:1605 INCA mAb will be a useful immunological probe in the study of NSCs. 26012782 9 51 theme INCA 1598:1601 arg1 probe 1638:1642 a useful immunological probe 1615:1642 a useful immunological probe 1615:1642 INCA mAb will be a useful immunological probe in the study of NSCs. 26012782 2 52 theme neural 343:348 arg1 antigens 355:362 immature neural cell antigens 334:362 immature neural cell antigens (INCA mAb) 334:373 We generated a novel monoclonal antibody (mAb), designated as mAb against immature neural cell antigens (INCA mAb), which reacted with the areas around a lateral ventricle of a fetal cerebrum. 26012782 2 52 theme neural 343:348 arg1 mAb 370:372 INCA mAb 365:372 INCA mAb 365:372 We generated a novel monoclonal antibody (mAb), designated as mAb against immature neural cell antigens (INCA mAb), which reacted with the areas around a lateral ventricle of a fetal cerebrum. 26012782 1 53 theme stem 241:244 arg1 NSCs 253:256 NSCs 253:256 NSCs 253:256 There are still few useful cell membrane surface antigens suitable for identification and isolation of neural stem cells (NSCs). 26012782 1 53 theme stem 241:244 arg1 cells 246:250 neural stem cells 234:250 neural stem cells (NSCs) 234:257 There are still few useful cell membrane surface antigens suitable for identification and isolation of neural stem cells (NSCs). 26012782 0 54 from Neurospheres 117:128 arg1 Characteristics 76:90 Characteristics 76:90 Characteristics of Its Positive Cells in Neurospheres 76:128 A Novel Monoclonal Antibody Against Neuroepithelial and Ependymal Cells and Characteristics of Its Positive Cells in Neurospheres. 26012782 0 54 from Neurospheres 117:128 arg1 Antibody 19:26 A Novel Monoclonal Antibody 0:26 A Novel Monoclonal Antibody Against Neuroepithelial and Ependymal Cells 0:70 A Novel Monoclonal Antibody Against Neuroepithelial and Ependymal Cells and Characteristics of Its Positive Cells in Neurospheres. 26012782 6 55 theme flow 1042:1045 arg1 analysis 1058:1065 A flow cytometric analysis 1040:1065 A flow cytometric analysis 1040:1065 A flow cytometric analysis showed that fetal and young adult neurospheres were divided into INCA mAb(-) CD133 polyclonal antibody (pAb)(-), INCA mAb(+) CD133 pAb(-), and INCA mAb(+) CD133 pAb(+) cell populations based on the reactivity against INCA mAb and CD133 pAb. 26012782 9 56 theme immunological 1624:1636 arg1 mAb 1603:1605 INCA mAb 1598:1605 INCA mAb 1598:1605 INCA mAb will be a useful immunological probe in the study of NSCs. 26012782 9 56 theme immunological 1624:1636 arg1 probe 1638:1642 a useful immunological probe 1615:1642 a useful immunological probe 1615:1642 INCA mAb will be a useful immunological probe in the study of NSCs. 26012782 2 57 theme novel 275:279 arg1 antibody 292:299 a novel monoclonal antibody 273:299 a novel monoclonal antibody (mAb) 273:305 We generated a novel monoclonal antibody (mAb), designated as mAb against immature neural cell antigens (INCA mAb), which reacted with the areas around a lateral ventricle of a fetal cerebrum. 26012782 2 57 theme novel 275:279 arg1 mAb 302:304 mAb 302:304 mAb 302:304 We generated a novel monoclonal antibody (mAb), designated as mAb against immature neural cell antigens (INCA mAb), which reacted with the areas around a lateral ventricle of a fetal cerebrum. 26012782 6 58 theme INCA 1180:1183 arg1 mAb 1185:1187 INCA mAb 1180:1187 INCA mAb 1180:1187 A flow cytometric analysis showed that fetal and young adult neurospheres were divided into INCA mAb(-) CD133 polyclonal antibody (pAb)(-), INCA mAb(+) CD133 pAb(-), and INCA mAb(+) CD133 pAb(+) cell populations based on the reactivity against INCA mAb and CD133 pAb. 26012782 5 59 theme stage-specific 822:835 arg1 antigen 837:843 a stage-specific antigen 820:843 a stage-specific antigen expressed on undifferentiated neuroepithelial cells 820:895 Based on expression pattern analysis of the recognition molecules in developing cerebrums, it was concluded that gp42 INCA was a stage-specific antigen expressed on undifferentiated neuroepithelial cells, while gp40 INCA was a cell lineage-specific antigen expressed at the stages of differentiation from neuroepithelial cells to ependymal cells. 26012782 5 59 theme stage-specific 822:835 arg1 INCA 811:814 gp42 INCA 806:814 gp42 INCA 806:814 Based on expression pattern analysis of the recognition molecules in developing cerebrums, it was concluded that gp42 INCA was a stage-specific antigen expressed on undifferentiated neuroepithelial cells, while gp40 INCA was a cell lineage-specific antigen expressed at the stages of differentiation from neuroepithelial cells to ependymal cells. 26012782 7 60 contain having 1332:1337 arg1 cells 1326:1330 cells 1326:1330 cells having the neurosphere formation capability in the INCA mAb(+) CD133 pAb(+) cell population 1326:1422 The proportion of cells having the neurosphere formation capability in the INCA mAb(+) CD133 pAb(+) cell population was significantly larger than that of undivided neurospheres. 26012782 7 60 contain having 1332:1337 arg2 capability 1365:1374 the neurosphere formation capability 1339:1374 the neurosphere formation capability in the INCA mAb(+) CD133 pAb(+) cell population 1339:1422 The proportion of cells having the neurosphere formation capability in the INCA mAb(+) CD133 pAb(+) cell population was significantly larger than that of undivided neurospheres. 26012782 1 61 theme membrane 163:170 arg1 antigens 180:187 few useful cell membrane surface antigens 147:187 few useful cell membrane surface antigens suitable for identification and isolation of neural stem cells (NSCs) 147:257 There are still few useful cell membrane surface antigens suitable for identification and isolation of neural stem cells (NSCs). 26012782 7 62 from capability 1365:1374 arg1 population 1413:1422 the INCA mAb(+) CD133 pAb(+) cell population 1379:1422 the INCA mAb(+) CD133 pAb(+) cell population 1379:1422 The proportion of cells having the neurosphere formation capability in the INCA mAb(+) CD133 pAb(+) cell population was significantly larger than that of undivided neurospheres. 26012782 8 63 theme clonal 1509:1514 arg1 expansion 1516:1524 clonal expansion 1509:1524 clonal expansion of INCA mAb(+) CD133 pAb(+) cells 1509:1558 Neurospheres formed by clonal expansion of INCA mAb(+) CD133 pAb(+) cells gave rise to neurons and glial cells. 26012782 5 64 theme gp42 806:809 arg1 antigen 837:843 a stage-specific antigen 820:843 a stage-specific antigen expressed on undifferentiated neuroepithelial cells 820:895 Based on expression pattern analysis of the recognition molecules in developing cerebrums, it was concluded that gp42 INCA was a stage-specific antigen expressed on undifferentiated neuroepithelial cells, while gp40 INCA was a cell lineage-specific antigen expressed at the stages of differentiation from neuroepithelial cells to ependymal cells. 26012782 5 64 theme gp42 806:809 arg1 INCA 811:814 gp42 INCA 806:814 gp42 INCA 806:814 Based on expression pattern analysis of the recognition molecules in developing cerebrums, it was concluded that gp42 INCA was a stage-specific antigen expressed on undifferentiated neuroepithelial cells, while gp40 INCA was a cell lineage-specific antigen expressed at the stages of differentiation from neuroepithelial cells to ependymal cells. 26012782 9 65 theme NSCs 1660:1663 arg1 study 1651:1655 the study 1647:1655 the study of NSCs 1647:1663 INCA mAb will be a useful immunological probe in the study of NSCs. 26012782 4 66 theme kDa 619:621 arg1 molecules 585:593 The recognition molecules 569:593 The recognition molecules 569:593 The recognition molecules were O-linked 40 and 42 kDa glycoproteins on the cell membrane surface (gp40 INCA and gp42 INCA). 26012782 4 66 theme kDa 619:621 arg1 glycoproteins 623:635 O-linked 40 and 42 kDa glycoproteins 600:635 O-linked 40 and 42 kDa glycoproteins 600:635 The recognition molecules were O-linked 40 and 42 kDa glycoproteins on the cell membrane surface (gp40 INCA and gp42 INCA). 26012782 7 67 theme cell 1408:1411 arg1 population 1413:1422 the INCA mAb(+) CD133 pAb(+) cell population 1379:1422 the INCA mAb(+) CD133 pAb(+) cell population 1379:1422 The proportion of cells having the neurosphere formation capability in the INCA mAb(+) CD133 pAb(+) cell population was significantly larger than that of undivided neurospheres. 26012782 6 68 theme adult 1095:1099 arg1 neurospheres 1101:1112 fetal and young adult neurospheres 1079:1112 fetal and young adult neurospheres 1079:1112 A flow cytometric analysis showed that fetal and young adult neurospheres were divided into INCA mAb(-) CD133 polyclonal antibody (pAb)(-), INCA mAb(+) CD133 pAb(-), and INCA mAb(+) CD133 pAb(+) cell populations based on the reactivity against INCA mAb and CD133 pAb. 26012782 5 69 from stages 967:972 arg1 cells 1014:1018 neuroepithelial cells 998:1018 neuroepithelial cells 998:1018 Based on expression pattern analysis of the recognition molecules in developing cerebrums, it was concluded that gp42 INCA was a stage-specific antigen expressed on undifferentiated neuroepithelial cells, while gp40 INCA was a cell lineage-specific antigen expressed at the stages of differentiation from neuroepithelial cells to ependymal cells. 26012782 6 70 theme pAb 1171:1173 arg1 populations 1240:1250 INCA mAb(-) CD133 polyclonal antibody (pAb)(-), INCA mAb(+) CD133 pAb(-), and INCA mAb(+) CD133 pAb(+) cell populations 1132:1250 INCA mAb(-) CD133 polyclonal antibody (pAb)(-), INCA mAb(+) CD133 pAb(-), and INCA mAb(+) CD133 pAb(+) cell populations based on the reactivity against INCA mAb and CD133 pAb 1132:1305 A flow cytometric analysis showed that fetal and young adult neurospheres were divided into INCA mAb(-) CD133 polyclonal antibody (pAb)(-), INCA mAb(+) CD133 pAb(-), and INCA mAb(+) CD133 pAb(+) cell populations based on the reactivity against INCA mAb and CD133 pAb. 26012782 4 71 theme O-linked 600:607 arg1 molecules 585:593 The recognition molecules 569:593 The recognition molecules 569:593 The recognition molecules were O-linked 40 and 42 kDa glycoproteins on the cell membrane surface (gp40 INCA and gp42 INCA). 26012782 4 71 theme O-linked 600:607 arg1 glycoproteins 623:635 O-linked 40 and 42 kDa glycoproteins 600:635 O-linked 40 and 42 kDa glycoproteins 600:635 The recognition molecules were O-linked 40 and 42 kDa glycoproteins on the cell membrane surface (gp40 INCA and gp42 INCA). 26012782 3 72 theme ependymal 533:541 arg1 cells 543:547 ependymal cells 533:547 ependymal cells 533:547 INCA mAb specifically reacted with neuroepithelial cells in fetal cerebrums and ependymal cells in adult cerebrums. 26012782 7 73 theme pAb 1401:1403 arg1 population 1413:1422 the INCA mAb(+) CD133 pAb(+) cell population 1379:1422 the INCA mAb(+) CD133 pAb(+) cell population 1379:1422 The proportion of cells having the neurosphere formation capability in the INCA mAb(+) CD133 pAb(+) cell population was significantly larger than that of undivided neurospheres. 26012782 6 74 theme antibody 1161:1168 arg1 pAb 1171:1173 CD133 polyclonal antibody (pAb)(-), INCA mAb(+) CD133 pAb(-), 1144:1204 pAb 1171:1173 A flow cytometric analysis showed that fetal and young adult neurospheres were divided into INCA mAb(-) CD133 polyclonal antibody (pAb)(-), INCA mAb(+) CD133 pAb(-), and INCA mAb(+) CD133 pAb(+) cell populations based on the reactivity against INCA mAb and CD133 pAb. 26012782 5 75 theme neuroepithelial 998:1012 arg1 cells 1014:1018 neuroepithelial cells 998:1018 neuroepithelial cells 998:1018 Based on expression pattern analysis of the recognition molecules in developing cerebrums, it was concluded that gp42 INCA was a stage-specific antigen expressed on undifferentiated neuroepithelial cells, while gp40 INCA was a cell lineage-specific antigen expressed at the stages of differentiation from neuroepithelial cells to ependymal cells. 26012782 8 76 theme CD133 1541:1545 arg1 pAb 1547:1549 CD133 pAb 1541:1549 CD133 pAb 1541:1549 Neurospheres formed by clonal expansion of INCA mAb(+) CD133 pAb(+) cells gave rise to neurons and glial cells. 26012782 5 77 theme undifferentiated 858:873 arg1 cells 891:895 undifferentiated neuroepithelial cells 858:895 undifferentiated neuroepithelial cells 858:895 Based on expression pattern analysis of the recognition molecules in developing cerebrums, it was concluded that gp42 INCA was a stage-specific antigen expressed on undifferentiated neuroepithelial cells, while gp40 INCA was a cell lineage-specific antigen expressed at the stages of differentiation from neuroepithelial cells to ependymal cells. 26012782 9 78 from probe 1638:1642 arg1 study 1651:1655 the study 1647:1655 the study of NSCs 1647:1663 INCA mAb will be a useful immunological probe in the study of NSCs. 26012782 4 79 link O-linked 600:607 arg1 molecules 585:593 The recognition molecules 569:593 The recognition molecules 569:593 The recognition molecules were O-linked 40 and 42 kDa glycoproteins on the cell membrane surface (gp40 INCA and gp42 INCA). 26012782 4 79 link O-linked 600:607 arg1 glycoproteins 623:635 O-linked 40 and 42 kDa glycoproteins 600:635 O-linked 40 and 42 kDa glycoproteins 600:635 The recognition molecules were O-linked 40 and 42 kDa glycoproteins on the cell membrane surface (gp40 INCA and gp42 INCA). 26012782 4 80 theme gp40 667:670 arg1 INCA 672:675 gp40 INCA 667:675 gp40 INCA 667:675 The recognition molecules were O-linked 40 and 42 kDa glycoproteins on the cell membrane surface (gp40 INCA and gp42 INCA). 26012782 3 81 from cerebrums 519:527 arg1 cerebrums 558:566 adult cerebrums 552:566 adult cerebrums 552:566 INCA mAb specifically reacted with neuroepithelial cells in fetal cerebrums and ependymal cells in adult cerebrums. 26012782 5 82 from cells 1014:1018 arg1 stages 967:972 the stages 963:972 the stages of differentiation from neuroepithelial cells to ependymal cells 963:1037 Based on expression pattern analysis of the recognition molecules in developing cerebrums, it was concluded that gp42 INCA was a stage-specific antigen expressed on undifferentiated neuroepithelial cells, while gp40 INCA was a cell lineage-specific antigen expressed at the stages of differentiation from neuroepithelial cells to ependymal cells. 26012782 5 82 from cells 1014:1018 arg1 differentiation 977:991 differentiation 977:991 differentiation from neuroepithelial cells to ependymal cells 977:1037 Based on expression pattern analysis of the recognition molecules in developing cerebrums, it was concluded that gp42 INCA was a stage-specific antigen expressed on undifferentiated neuroepithelial cells, while gp40 INCA was a cell lineage-specific antigen expressed at the stages of differentiation from neuroepithelial cells to ependymal cells. 26012782 3 83 from cells 504:508 arg1 cerebrums 519:527 fetal cerebrums 513:527 fetal cerebrums 513:527 INCA mAb specifically reacted with neuroepithelial cells in fetal cerebrums and ependymal cells in adult cerebrums. 26012782 3 83 from cells 504:508 arg1 cells 543:547 ependymal cells 533:547 ependymal cells 533:547 INCA mAb specifically reacted with neuroepithelial cells in fetal cerebrums and ependymal cells in adult cerebrums. 26012782 2 84 theme fetal 437:441 arg1 cerebrum 443:450 a fetal cerebrum 435:450 a fetal cerebrum 435:450 We generated a novel monoclonal antibody (mAb), designated as mAb against immature neural cell antigens (INCA mAb), which reacted with the areas around a lateral ventricle of a fetal cerebrum. 26012782 0 85 from Antibody 19:26 arg1 Neurospheres 117:128 Neurospheres 117:128 Neurospheres 117:128 A Novel Monoclonal Antibody Against Neuroepithelial and Ependymal Cells and Characteristics of Its Positive Cells in Neurospheres. 26012782 1 86 theme useful 151:156 arg1 antigens 180:187 few useful cell membrane surface antigens 147:187 few useful cell membrane surface antigens suitable for identification and isolation of neural stem cells (NSCs) 147:257 There are still few useful cell membrane surface antigens suitable for identification and isolation of neural stem cells (NSCs). 26012782 7 87 theme INCA 1383:1386 arg1 mAb 1388:1390 INCA mAb 1383:1390 INCA mAb 1383:1390 The proportion of cells having the neurosphere formation capability in the INCA mAb(+) CD133 pAb(+) cell population was significantly larger than that of undivided neurospheres. 26012782 4 88 theme cell 644:647 arg1 surface 658:664 the cell membrane surface 640:664 the cell membrane surface (gp40 INCA and gp42 INCA) 640:690 The recognition molecules were O-linked 40 and 42 kDa glycoproteins on the cell membrane surface (gp40 INCA and gp42 INCA). 26012782 0 89 theme Positive 99:106 arg1 Cells 108:112 Its Positive Cells 95:112 Its Positive Cells in Neurospheres 95:128 A Novel Monoclonal Antibody Against Neuroepithelial and Ependymal Cells and Characteristics of Its Positive Cells in Neurospheres. 26012782 5 90 from analysis 721:728 arg1 cerebrums 773:781 developing cerebrums 762:781 developing cerebrums 762:781 Based on expression pattern analysis of the recognition molecules in developing cerebrums, it was concluded that gp42 INCA was a stage-specific antigen expressed on undifferentiated neuroepithelial cells, while gp40 INCA was a cell lineage-specific antigen expressed at the stages of differentiation from neuroepithelial cells to ependymal cells. 26012782 2 91 theme monoclonal 281:290 arg1 antibody 292:299 a novel monoclonal antibody 273:299 a novel monoclonal antibody (mAb) 273:305 We generated a novel monoclonal antibody (mAb), designated as mAb against immature neural cell antigens (INCA mAb), which reacted with the areas around a lateral ventricle of a fetal cerebrum. 26012782 2 91 theme monoclonal 281:290 arg1 mAb 302:304 mAb 302:304 mAb 302:304 We generated a novel monoclonal antibody (mAb), designated as mAb against immature neural cell antigens (INCA mAb), which reacted with the areas around a lateral ventricle of a fetal cerebrum. 26012782 6 92 theme mAb 1215:1217 arg1 populations 1240:1250 INCA mAb(-) CD133 polyclonal antibody (pAb)(-), INCA mAb(+) CD133 pAb(-), and INCA mAb(+) CD133 pAb(+) cell populations 1132:1250 INCA mAb(-) CD133 polyclonal antibody (pAb)(-), INCA mAb(+) CD133 pAb(-), and INCA mAb(+) CD133 pAb(+) cell populations based on the reactivity against INCA mAb and CD133 pAb 1132:1305 A flow cytometric analysis showed that fetal and young adult neurospheres were divided into INCA mAb(-) CD133 polyclonal antibody (pAb)(-), INCA mAb(+) CD133 pAb(-), and INCA mAb(+) CD133 pAb(+) cell populations based on the reactivity against INCA mAb and CD133 pAb. 26012782 5 93 theme recognition 737:747 arg1 molecules 749:757 the recognition molecules 733:757 the recognition molecules in developing cerebrums 733:781 Based on expression pattern analysis of the recognition molecules in developing cerebrums, it was concluded that gp42 INCA was a stage-specific antigen expressed on undifferentiated neuroepithelial cells, while gp40 INCA was a cell lineage-specific antigen expressed at the stages of differentiation from neuroepithelial cells to ependymal cells. 26012782 5 94 from molecules 749:757 arg1 cerebrums 773:781 developing cerebrums 762:781 developing cerebrums 762:781 Based on expression pattern analysis of the recognition molecules in developing cerebrums, it was concluded that gp42 INCA was a stage-specific antigen expressed on undifferentiated neuroepithelial cells, while gp40 INCA was a cell lineage-specific antigen expressed at the stages of differentiation from neuroepithelial cells to ependymal cells. 26012782 2 95 theme cell 350:353 arg1 antigens 355:362 immature neural cell antigens 334:362 immature neural cell antigens (INCA mAb) 334:373 We generated a novel monoclonal antibody (mAb), designated as mAb against immature neural cell antigens (INCA mAb), which reacted with the areas around a lateral ventricle of a fetal cerebrum. 26012782 2 95 theme cell 350:353 arg1 mAb 370:372 INCA mAb 365:372 INCA mAb 365:372 We generated a novel monoclonal antibody (mAb), designated as mAb against immature neural cell antigens (INCA mAb), which reacted with the areas around a lateral ventricle of a fetal cerebrum. 26012782 8 96 theme mAb 1534:1536 arg1 cells 1554:1558 INCA mAb(+) CD133 pAb(+) cells 1529:1558 INCA mAb(+) CD133 pAb(+) cells 1529:1558 Neurospheres formed by clonal expansion of INCA mAb(+) CD133 pAb(+) cells gave rise to neurons and glial cells. 26012782 5 97 theme pattern 713:719 arg1 analysis 721:728 expression pattern analysis 702:728 expression pattern analysis of the recognition molecules in developing cerebrums 702:781 Based on expression pattern analysis of the recognition molecules in developing cerebrums, it was concluded that gp42 INCA was a stage-specific antigen expressed on undifferentiated neuroepithelial cells, while gp40 INCA was a cell lineage-specific antigen expressed at the stages of differentiation from neuroepithelial cells to ependymal cells. 26012782 2 98 theme lateral 414:420 arg1 ventricle 422:430 a lateral ventricle 412:430 a lateral ventricle of a fetal cerebrum 412:450 We generated a novel monoclonal antibody (mAb), designated as mAb against immature neural cell antigens (INCA mAb), which reacted with the areas around a lateral ventricle of a fetal cerebrum. 26012782 6 99 theme INCA 1210:1213 arg1 mAb 1215:1217 INCA mAb 1210:1217 INCA mAb 1210:1217 A flow cytometric analysis showed that fetal and young adult neurospheres were divided into INCA mAb(-) CD133 polyclonal antibody (pAb)(-), INCA mAb(+) CD133 pAb(-), and INCA mAb(+) CD133 pAb(+) cell populations based on the reactivity against INCA mAb and CD133 pAb. 26012782 0 100 theme Ependymal 56:64 arg1 Cells 66:70 Neuroepithelial and Ependymal Cells 36:70 Cells 66:70 A Novel Monoclonal Antibody Against Neuroepithelial and Ependymal Cells and Characteristics of Its Positive Cells in Neurospheres. 26012782 7 101 theme neurosphere 1343:1353 arg1 capability 1365:1374 the neurosphere formation capability 1339:1374 the neurosphere formation capability in the INCA mAb(+) CD133 pAb(+) cell population 1339:1422 The proportion of cells having the neurosphere formation capability in the INCA mAb(+) CD133 pAb(+) cell population was significantly larger than that of undivided neurospheres. 26012782 6 102 theme young 1089:1093 arg1 neurospheres 1101:1112 fetal and young adult neurospheres 1079:1112 fetal and young adult neurospheres 1079:1112 A flow cytometric analysis showed that fetal and young adult neurospheres were divided into INCA mAb(-) CD133 polyclonal antibody (pAb)(-), INCA mAb(+) CD133 pAb(-), and INCA mAb(+) CD133 pAb(+) cell populations based on the reactivity against INCA mAb and CD133 pAb. 26012782 5 103 theme lineage-specific 925:940 arg1 antigen 942:948 a cell lineage-specific antigen 918:948 a cell lineage-specific antigen expressed at the stages of differentiation from neuroepithelial cells to ependymal cells 918:1037 Based on expression pattern analysis of the recognition molecules in developing cerebrums, it was concluded that gp42 INCA was a stage-specific antigen expressed on undifferentiated neuroepithelial cells, while gp40 INCA was a cell lineage-specific antigen expressed at the stages of differentiation from neuroepithelial cells to ependymal cells. 26012782 5 103 theme lineage-specific 925:940 arg1 INCA 909:912 gp40 INCA 904:912 gp40 INCA 904:912 Based on expression pattern analysis of the recognition molecules in developing cerebrums, it was concluded that gp42 INCA was a stage-specific antigen expressed on undifferentiated neuroepithelial cells, while gp40 INCA was a cell lineage-specific antigen expressed at the stages of differentiation from neuroepithelial cells to ependymal cells. 26012782 6 104 theme fetal 1079:1083 arg1 neurospheres 1101:1112 fetal and young adult neurospheres 1079:1112 fetal and young adult neurospheres 1079:1112 A flow cytometric analysis showed that fetal and young adult neurospheres were divided into INCA mAb(-) CD133 polyclonal antibody (pAb)(-), INCA mAb(+) CD133 pAb(-), and INCA mAb(+) CD133 pAb(+) cell populations based on the reactivity against INCA mAb and CD133 pAb. 26012782 2 105 theme immature 334:341 arg1 antigens 355:362 immature neural cell antigens 334:362 immature neural cell antigens (INCA mAb) 334:373 We generated a novel monoclonal antibody (mAb), designated as mAb against immature neural cell antigens (INCA mAb), which reacted with the areas around a lateral ventricle of a fetal cerebrum. 26012782 2 105 theme immature 334:341 arg1 mAb 370:372 INCA mAb 365:372 INCA mAb 365:372 We generated a novel monoclonal antibody (mAb), designated as mAb against immature neural cell antigens (INCA mAb), which reacted with the areas around a lateral ventricle of a fetal cerebrum. 26012782 1 106 theme neural 234:239 arg1 NSCs 253:256 NSCs 253:256 NSCs 253:256 There are still few useful cell membrane surface antigens suitable for identification and isolation of neural stem cells (NSCs). 26012782 1 106 theme neural 234:239 arg1 cells 246:250 neural stem cells 234:250 neural stem cells (NSCs) 234:257 There are still few useful cell membrane surface antigens suitable for identification and isolation of neural stem cells (NSCs). 26012782 4 107 theme recognition 573:583 arg1 molecules 585:593 The recognition molecules 569:593 The recognition molecules 569:593 The recognition molecules were O-linked 40 and 42 kDa glycoproteins on the cell membrane surface (gp40 INCA and gp42 INCA). 26012782 4 107 theme recognition 573:583 arg1 glycoproteins 623:635 O-linked 40 and 42 kDa glycoproteins 600:635 O-linked 40 and 42 kDa glycoproteins 600:635 The recognition molecules were O-linked 40 and 42 kDa glycoproteins on the cell membrane surface (gp40 INCA and gp42 INCA). 26012782 0 108 theme Novel 2:6 arg1 Antibody 19:26 A Novel Monoclonal Antibody 0:26 A Novel Monoclonal Antibody Against Neuroepithelial and Ependymal Cells 0:70 A Novel Monoclonal Antibody Against Neuroepithelial and Ependymal Cells and Characteristics of Its Positive Cells in Neurospheres. 26012782 1 109 theme cells 246:250 arg1 identification 202:215 identification 202:215 identification 202:215 There are still few useful cell membrane surface antigens suitable for identification and isolation of neural stem cells (NSCs). 26012782 1 109 theme cells 246:250 arg1 isolation 221:229 isolation 221:229 isolation 221:229 There are still few useful cell membrane surface antigens suitable for identification and isolation of neural stem cells (NSCs). 25230886 4 0 dep patients 544:551 arg1 MO 557:558 27 MO 554:558 27 MO 554:558 We present the clinical and molecular analysis of 33 unrelated Latin American patients (27 MO and 6 SO). 25230886 4 0 dep patients 544:551 arg1 6 564:564 6 564:564 6 564:564 We present the clinical and molecular analysis of 33 unrelated Latin American patients (27 MO and 6 SO). 25230886 9 1 theme nonsense 975:982 arg1 mutation 989:996 a nonsense EXT1 mutation 973:996 a nonsense EXT1 mutation 973:996 No second mutational hit was detected in the DNA of the secondary chondrosarcoma from a patient who carried a nonsense EXT1 mutation. 25230886 9 2 theme second 868:873 arg1 hit 886:888 No second mutational hit 865:888 No second mutational hit 865:888 No second mutational hit was detected in the DNA of the secondary chondrosarcoma from a patient who carried a nonsense EXT1 mutation. 25230886 4 3 theme unrelated 519:527 arg1 patients 544:551 33 unrelated Latin American patients 516:551 33 unrelated Latin American patients (27 MO and 6 SO) 516:568 We present the clinical and molecular analysis of 33 unrelated Latin American patients (27 MO and 6 SO). 25230886 1 4 theme autosomal 141:149 arg1 osteochondromatosis 91:109 Multiple osteochondromatosis 82:109 Multiple osteochondromatosis (MO) 82:114 Multiple osteochondromatosis (MO), or EXT1/EXT2-CDG, is an autosomal dominant O-linked glycosylation disorder characterized by the formation of multiple cartilage-capped tumors (osteochondromas). 25230886 1 4 theme autosomal 141:149 arg1 disorder 183:190 an autosomal dominant O-linked glycosylation disorder 138:190 an autosomal dominant O-linked glycosylation disorder characterized by the formation of multiple cartilage-capped tumors (osteochondromas) 138:275 Multiple osteochondromatosis (MO), or EXT1/EXT2-CDG, is an autosomal dominant O-linked glycosylation disorder characterized by the formation of multiple cartilage-capped tumors (osteochondromas). 25230886 1 4 theme autosomal 141:149 arg1 EXT1/EXT2-CDG 120:132 EXT1/EXT2-CDG 120:132 EXT1/EXT2-CDG 120:132 Multiple osteochondromatosis (MO), or EXT1/EXT2-CDG, is an autosomal dominant O-linked glycosylation disorder characterized by the formation of multiple cartilage-capped tumors (osteochondromas). 25230886 9 5 theme EXT1 984:987 arg1 mutation 989:996 a nonsense EXT1 mutation 973:996 a nonsense EXT1 mutation 973:996 No second mutational hit was detected in the DNA of the secondary chondrosarcoma from a patient who carried a nonsense EXT1 mutation. 25230886 9 6 theme mutational 875:884 arg1 hit 886:888 No second mutational hit 865:888 No second mutational hit 865:888 No second mutational hit was detected in the DNA of the secondary chondrosarcoma from a patient who carried a nonsense EXT1 mutation. 25230886 5 7 theme malignant 642:650 arg1 transformations 652:666 two malignant transformations 638:666 two malignant transformations to chondrosarcoma (7%) 638:689 Sixty-three percent of all MO cases presented severe phenotype and two malignant transformations to chondrosarcoma (7%). 25230886 2 8 theme solitary 291:298 arg1 condition 340:348 a non-hereditary condition 323:348 a non-hereditary condition 323:348 In contrast, solitary osteochondroma (SO) is a non-hereditary condition. 25230886 2 8 theme solitary 291:298 arg1 osteochondroma 300:313 solitary osteochondroma 291:313 solitary osteochondroma (SO) 291:318 In contrast, solitary osteochondroma (SO) is a non-hereditary condition. 25230886 4 9 theme clinical 481:488 arg1 analysis 504:511 the clinical and molecular analysis 477:511 the clinical and molecular analysis of 33 unrelated Latin American patients (27 MO and 6 SO) 477:568 We present the clinical and molecular analysis of 33 unrelated Latin American patients (27 MO and 6 SO). 25230886 2 10 from condition 340:348 arg1 contrast 281:288 contrast 281:288 contrast 281:288 In contrast, solitary osteochondroma (SO) is a non-hereditary condition. 25230886 11 11 theme research 1096:1103 arg1 This 1063:1066 This 1063:1066 This 1063:1066 This is the first Latin American research program on EXT1/EXT2-CDG. 25230886 11 11 theme research 1096:1103 arg1 program 1105:1111 the first Latin American research program 1071:1111 the first Latin American research program on EXT1/EXT2-CDG 1071:1128 This is the first Latin American research program on EXT1/EXT2-CDG. 25230886 5 12 theme Sixty-three 571:581 arg1 percent 583:589 Sixty-three percent 571:589 Sixty-three percent of all MO cases 571:605 Sixty-three percent of all MO cases presented severe phenotype and two malignant transformations to chondrosarcoma (7%). 25230886 5 13 theme cases 601:605 arg1 percent 583:589 Sixty-three percent 571:589 Sixty-three percent of all MO cases 571:605 Sixty-three percent of all MO cases presented severe phenotype and two malignant transformations to chondrosarcoma (7%). 25230886 0 14 with patients 53:60 arg1 EXT1/EXT2-CDG 67:79 EXT1/EXT2-CDG 67:79 EXT1/EXT2-CDG 67:79 A broad spectrum of genomic changes in latinamerican patients with EXT1/EXT2-CDG. 25230886 11 15 theme first 1075:1079 arg1 This 1063:1066 This 1063:1066 This 1063:1066 This is the first Latin American research program on EXT1/EXT2-CDG. 25230886 11 15 theme first 1075:1079 arg1 program 1105:1111 the first Latin American research program 1071:1111 the first Latin American research program on EXT1/EXT2-CDG 1071:1128 This is the first Latin American research program on EXT1/EXT2-CDG. 25230886 1 16 theme dominant 151:158 arg1 osteochondromatosis 91:109 Multiple osteochondromatosis 82:109 Multiple osteochondromatosis (MO) 82:114 Multiple osteochondromatosis (MO), or EXT1/EXT2-CDG, is an autosomal dominant O-linked glycosylation disorder characterized by the formation of multiple cartilage-capped tumors (osteochondromas). 25230886 1 16 theme dominant 151:158 arg1 disorder 183:190 an autosomal dominant O-linked glycosylation disorder 138:190 an autosomal dominant O-linked glycosylation disorder characterized by the formation of multiple cartilage-capped tumors (osteochondromas) 138:275 Multiple osteochondromatosis (MO), or EXT1/EXT2-CDG, is an autosomal dominant O-linked glycosylation disorder characterized by the formation of multiple cartilage-capped tumors (osteochondromas). 25230886 1 16 theme dominant 151:158 arg1 EXT1/EXT2-CDG 120:132 EXT1/EXT2-CDG 120:132 EXT1/EXT2-CDG 120:132 Multiple osteochondromatosis (MO), or EXT1/EXT2-CDG, is an autosomal dominant O-linked glycosylation disorder characterized by the formation of multiple cartilage-capped tumors (osteochondromas). 25230886 4 17 theme molecular 494:502 arg1 analysis 504:511 the clinical and molecular analysis 477:511 the clinical and molecular analysis of 33 unrelated Latin American patients (27 MO and 6 SO) 477:568 We present the clinical and molecular analysis of 33 unrelated Latin American patients (27 MO and 6 SO). 25230886 8 18 theme patients 832:839 arg1 patients 832:839 the MO patients 825:839 the MO patients 825:839 The disease-causing mutations remained unknown in 22% of the MO patients and in all SO patients. 25230886 8 18 theme patients 832:839 arg1 % 820:820 22% 818:820 22% of the MO patients 818:839 The disease-causing mutations remained unknown in 22% of the MO patients and in all SO patients. 25230886 3 19 theme sulfate 446:452 arg1 elongation 454:463 heparan sulfate elongation 438:463 heparan sulfate elongation 438:463 EXT1 and EXT2, are tumor suppressor genes that encode glycosyltransferases involved in heparan sulfate elongation. 25230886 0 20 theme broad 2:6 arg1 spectrum 8:15 A broad spectrum 0:15 A broad spectrum of genomic 0:26 A broad spectrum of genomic changes in latinamerican patients with EXT1/EXT2-CDG. 25230886 10 21 theme EXT2 1016:1019 arg1 protein 1021:1027 EXT2 protein 1016:1027 EXT2 protein 1016:1027 Neither EXT1 nor EXT2 protein could be detected in this sample. 25230886 5 22 theme severe 617:622 arg1 phenotype 624:632 severe phenotype 617:632 severe phenotype 617:632 Sixty-three percent of all MO cases presented severe phenotype and two malignant transformations to chondrosarcoma (7%). 25230886 1 23 theme Multiple 82:89 arg1 osteochondromatosis 91:109 Multiple osteochondromatosis 82:109 Multiple osteochondromatosis (MO) 82:114 Multiple osteochondromatosis (MO), or EXT1/EXT2-CDG, is an autosomal dominant O-linked glycosylation disorder characterized by the formation of multiple cartilage-capped tumors (osteochondromas). 25230886 1 23 theme Multiple 82:89 arg1 disorder 183:190 an autosomal dominant O-linked glycosylation disorder 138:190 an autosomal dominant O-linked glycosylation disorder characterized by the formation of multiple cartilage-capped tumors (osteochondromas) 138:275 Multiple osteochondromatosis (MO), or EXT1/EXT2-CDG, is an autosomal dominant O-linked glycosylation disorder characterized by the formation of multiple cartilage-capped tumors (osteochondromas). 25230886 1 23 theme Multiple 82:89 arg1 EXT1/EXT2-CDG 120:132 EXT1/EXT2-CDG 120:132 EXT1/EXT2-CDG 120:132 Multiple osteochondromatosis (MO), or EXT1/EXT2-CDG, is an autosomal dominant O-linked glycosylation disorder characterized by the formation of multiple cartilage-capped tumors (osteochondromas). 25230886 1 23 theme Multiple 82:89 arg1 MO 112:113 MO 112:113 MO 112:113 Multiple osteochondromatosis (MO), or EXT1/EXT2-CDG, is an autosomal dominant O-linked glycosylation disorder characterized by the formation of multiple cartilage-capped tumors (osteochondromas). 25230886 8 24 theme MO 829:830 arg1 patients 832:839 the MO patients 825:839 the MO patients 825:839 The disease-causing mutations remained unknown in 22% of the MO patients and in all SO patients. 25230886 1 25 theme glycosylation 169:181 arg1 osteochondromatosis 91:109 Multiple osteochondromatosis 82:109 Multiple osteochondromatosis (MO) 82:114 Multiple osteochondromatosis (MO), or EXT1/EXT2-CDG, is an autosomal dominant O-linked glycosylation disorder characterized by the formation of multiple cartilage-capped tumors (osteochondromas). 25230886 1 25 theme glycosylation 169:181 arg1 disorder 183:190 an autosomal dominant O-linked glycosylation disorder 138:190 an autosomal dominant O-linked glycosylation disorder characterized by the formation of multiple cartilage-capped tumors (osteochondromas) 138:275 Multiple osteochondromatosis (MO), or EXT1/EXT2-CDG, is an autosomal dominant O-linked glycosylation disorder characterized by the formation of multiple cartilage-capped tumors (osteochondromas). 25230886 1 25 theme glycosylation 169:181 arg1 EXT1/EXT2-CDG 120:132 EXT1/EXT2-CDG 120:132 EXT1/EXT2-CDG 120:132 Multiple osteochondromatosis (MO), or EXT1/EXT2-CDG, is an autosomal dominant O-linked glycosylation disorder characterized by the formation of multiple cartilage-capped tumors (osteochondromas). 25230886 3 26 theme suppressor 376:385 arg1 EXT1 351:354 EXT1 351:354 EXT1 351:354 EXT1 and EXT2, are tumor suppressor genes that encode glycosyltransferases involved in heparan sulfate elongation. 25230886 3 26 theme suppressor 376:385 arg1 EXT2 360:363 EXT2 360:363 EXT2 360:363 EXT1 and EXT2, are tumor suppressor genes that encode glycosyltransferases involved in heparan sulfate elongation. 25230886 3 26 theme suppressor 376:385 arg1 genes 387:391 tumor suppressor genes 370:391 tumor suppressor genes that encode glycosyltransferases involved in heparan sulfate elongation 370:463 EXT1 and EXT2, are tumor suppressor genes that encode glycosyltransferases involved in heparan sulfate elongation. 25230886 3 26 theme suppressor 376:385 arg1 glycosyltransferases 405:424 glycosyltransferases 405:424 glycosyltransferases involved in heparan sulfate elongation 405:463 EXT1 and EXT2, are tumor suppressor genes that encode glycosyltransferases involved in heparan sulfate elongation. 25230886 1 27 link O-linked 160:167 arg1 osteochondromatosis 91:109 Multiple osteochondromatosis 82:109 Multiple osteochondromatosis (MO) 82:114 Multiple osteochondromatosis (MO), or EXT1/EXT2-CDG, is an autosomal dominant O-linked glycosylation disorder characterized by the formation of multiple cartilage-capped tumors (osteochondromas). 25230886 1 27 link O-linked 160:167 arg1 disorder 183:190 an autosomal dominant O-linked glycosylation disorder 138:190 an autosomal dominant O-linked glycosylation disorder characterized by the formation of multiple cartilage-capped tumors (osteochondromas) 138:275 Multiple osteochondromatosis (MO), or EXT1/EXT2-CDG, is an autosomal dominant O-linked glycosylation disorder characterized by the formation of multiple cartilage-capped tumors (osteochondromas). 25230886 1 27 link O-linked 160:167 arg1 EXT1/EXT2-CDG 120:132 EXT1/EXT2-CDG 120:132 EXT1/EXT2-CDG 120:132 Multiple osteochondromatosis (MO), or EXT1/EXT2-CDG, is an autosomal dominant O-linked glycosylation disorder characterized by the formation of multiple cartilage-capped tumors (osteochondromas). 25230886 6 28 theme patients 732:739 arg1 % 724:724 78% 722:724 78% of MO patients 722:739 We found the mutant allele in 78% of MO patients. 25230886 6 28 theme patients 732:739 arg1 patients 732:739 MO patients 729:739 MO patients 729:739 We found the mutant allele in 78% of MO patients. 25230886 5 29 theme MO 598:599 arg1 cases 601:605 all MO cases 594:605 all MO cases 594:605 Sixty-three percent of all MO cases presented severe phenotype and two malignant transformations to chondrosarcoma (7%). 25230886 9 30 located detected 894:901 arg1 DNA 910:912 the DNA 906:912 the DNA of the secondary chondrosarcoma from a patient who carried a nonsense EXT1 mutation 906:996 No second mutational hit was detected in the DNA of the secondary chondrosarcoma from a patient who carried a nonsense EXT1 mutation. 25230886 9 30 located detected 894:901 arg2 hit 886:888 No second mutational hit 865:888 No second mutational hit 865:888 No second mutational hit was detected in the DNA of the secondary chondrosarcoma from a patient who carried a nonsense EXT1 mutation. 25230886 9 31 contain carried 965:971 arg2 mutation 989:996 a nonsense EXT1 mutation 973:996 a nonsense EXT1 mutation 973:996 No second mutational hit was detected in the DNA of the secondary chondrosarcoma from a patient who carried a nonsense EXT1 mutation. 25230886 9 31 contain carried 965:971 arg1 patient 953:959 a patient 951:959 a patient who carried a nonsense EXT1 mutation 951:996 No second mutational hit was detected in the DNA of the secondary chondrosarcoma from a patient who carried a nonsense EXT1 mutation. 25230886 9 32 from patient 953:959 arg1 DNA 910:912 the DNA 906:912 the DNA of the secondary chondrosarcoma from a patient who carried a nonsense EXT1 mutation 906:996 No second mutational hit was detected in the DNA of the secondary chondrosarcoma from a patient who carried a nonsense EXT1 mutation. 25230886 2 33 dep osteochondroma 300:313 arg1 SO 316:317 SO 316:317 SO 316:317 In contrast, solitary osteochondroma (SO) is a non-hereditary condition. 25230886 0 34 theme genomic 20:26 arg1 spectrum 8:15 A broad spectrum 0:15 A broad spectrum of genomic 0:26 A broad spectrum of genomic changes in latinamerican patients with EXT1/EXT2-CDG. 25230886 4 35 theme American 535:542 arg1 patients 544:551 33 unrelated Latin American patients 516:551 33 unrelated Latin American patients (27 MO and 6 SO) 516:568 We present the clinical and molecular analysis of 33 unrelated Latin American patients (27 MO and 6 SO). 25230886 9 36 theme secondary 921:929 arg1 chondrosarcoma 931:944 the secondary chondrosarcoma 917:944 the secondary chondrosarcoma 917:944 No second mutational hit was detected in the DNA of the secondary chondrosarcoma from a patient who carried a nonsense EXT1 mutation. 25230886 0 37 theme latinamerican 39:51 arg1 patients 53:60 latinamerican patients 39:60 latinamerican patients with EXT1/EXT2-CDG 39:79 A broad spectrum of genomic changes in latinamerican patients with EXT1/EXT2-CDG. 25230886 3 38 theme heparan 438:444 arg1 elongation 454:463 heparan sulfate elongation 438:463 heparan sulfate elongation 438:463 EXT1 and EXT2, are tumor suppressor genes that encode glycosyltransferases involved in heparan sulfate elongation. 25230886 6 39 theme MO 729:730 arg1 patients 732:739 MO patients 729:739 MO patients 729:739 We found the mutant allele in 78% of MO patients. 25230886 2 40 theme non-hereditary 325:338 arg1 condition 340:348 a non-hereditary condition 323:348 a non-hereditary condition 323:348 In contrast, solitary osteochondroma (SO) is a non-hereditary condition. 25230886 2 40 theme non-hereditary 325:338 arg1 osteochondroma 300:313 solitary osteochondroma 291:313 solitary osteochondroma (SO) 291:318 In contrast, solitary osteochondroma (SO) is a non-hereditary condition. 25230886 8 41 theme disease-causing 772:786 arg1 mutations 788:796 The disease-causing mutations 768:796 The disease-causing mutations 768:796 The disease-causing mutations remained unknown in 22% of the MO patients and in all SO patients. 25230886 4 42 theme patients 544:551 arg1 analysis 504:511 the clinical and molecular analysis 477:511 the clinical and molecular analysis of 33 unrelated Latin American patients (27 MO and 6 SO) 477:568 We present the clinical and molecular analysis of 33 unrelated Latin American patients (27 MO and 6 SO). 25230886 11 43 from program 1105:1111 arg1 EXT1/EXT2-CDG 1116:1128 EXT1/EXT2-CDG 1116:1128 EXT1/EXT2-CDG 1116:1128 This is the first Latin American research program on EXT1/EXT2-CDG. 25230886 11 44 theme American 1087:1094 arg1 This 1063:1066 This 1063:1066 This 1063:1066 This is the first Latin American research program on EXT1/EXT2-CDG. 25230886 11 44 theme American 1087:1094 arg1 program 1105:1111 the first Latin American research program 1071:1111 the first Latin American research program on EXT1/EXT2-CDG 1071:1128 This is the first Latin American research program on EXT1/EXT2-CDG. 25230886 1 45 theme multiple 226:233 arg1 osteochondromas 260:274 osteochondromas 260:274 osteochondromas 260:274 Multiple osteochondromatosis (MO), or EXT1/EXT2-CDG, is an autosomal dominant O-linked glycosylation disorder characterized by the formation of multiple cartilage-capped tumors (osteochondromas). 25230886 1 45 theme multiple 226:233 arg1 tumors 252:257 multiple cartilage-capped tumors 226:257 multiple cartilage-capped tumors (osteochondromas) 226:275 Multiple osteochondromatosis (MO), or EXT1/EXT2-CDG, is an autosomal dominant O-linked glycosylation disorder characterized by the formation of multiple cartilage-capped tumors (osteochondromas). 25230886 6 46 theme mutant 705:710 arg1 allele 712:717 the mutant allele 701:717 the mutant allele 701:717 We found the mutant allele in 78% of MO patients. 25230886 1 47 theme O-linked 160:167 arg1 osteochondromatosis 91:109 Multiple osteochondromatosis 82:109 Multiple osteochondromatosis (MO) 82:114 Multiple osteochondromatosis (MO), or EXT1/EXT2-CDG, is an autosomal dominant O-linked glycosylation disorder characterized by the formation of multiple cartilage-capped tumors (osteochondromas). 25230886 1 47 theme O-linked 160:167 arg1 disorder 183:190 an autosomal dominant O-linked glycosylation disorder 138:190 an autosomal dominant O-linked glycosylation disorder characterized by the formation of multiple cartilage-capped tumors (osteochondromas) 138:275 Multiple osteochondromatosis (MO), or EXT1/EXT2-CDG, is an autosomal dominant O-linked glycosylation disorder characterized by the formation of multiple cartilage-capped tumors (osteochondromas). 25230886 1 47 theme O-linked 160:167 arg1 EXT1/EXT2-CDG 120:132 EXT1/EXT2-CDG 120:132 EXT1/EXT2-CDG 120:132 Multiple osteochondromatosis (MO), or EXT1/EXT2-CDG, is an autosomal dominant O-linked glycosylation disorder characterized by the formation of multiple cartilage-capped tumors (osteochondromas). 25230886 1 48 theme cartilage-capped 235:250 arg1 osteochondromas 260:274 osteochondromas 260:274 osteochondromas 260:274 Multiple osteochondromatosis (MO), or EXT1/EXT2-CDG, is an autosomal dominant O-linked glycosylation disorder characterized by the formation of multiple cartilage-capped tumors (osteochondromas). 25230886 1 48 theme cartilage-capped 235:250 arg1 tumors 252:257 multiple cartilage-capped tumors 226:257 multiple cartilage-capped tumors (osteochondromas) 226:275 Multiple osteochondromatosis (MO), or EXT1/EXT2-CDG, is an autosomal dominant O-linked glycosylation disorder characterized by the formation of multiple cartilage-capped tumors (osteochondromas). 25230886 9 49 theme chondrosarcoma 931:944 arg1 DNA 910:912 the DNA 906:912 the DNA of the secondary chondrosarcoma from a patient who carried a nonsense EXT1 mutation 906:996 No second mutational hit was detected in the DNA of the secondary chondrosarcoma from a patient who carried a nonsense EXT1 mutation. 25230886 10 50 located detected 1038:1045 arg2 protein 1021:1027 EXT2 protein 1016:1027 EXT2 protein 1016:1027 Neither EXT1 nor EXT2 protein could be detected in this sample. 25230886 10 50 located detected 1038:1045 arg1 sample 1055:1060 this sample 1050:1060 this sample 1050:1060 Neither EXT1 nor EXT2 protein could be detected in this sample. 25230886 10 50 located detected 1038:1045 arg2 EXT1 1007:1010 EXT1 1007:1010 EXT1 1007:1010 Neither EXT1 nor EXT2 protein could be detected in this sample. 25230886 3 51 theme tumor 370:374 arg1 EXT1 351:354 EXT1 351:354 EXT1 351:354 EXT1 and EXT2, are tumor suppressor genes that encode glycosyltransferases involved in heparan sulfate elongation. 25230886 3 51 theme tumor 370:374 arg1 EXT2 360:363 EXT2 360:363 EXT2 360:363 EXT1 and EXT2, are tumor suppressor genes that encode glycosyltransferases involved in heparan sulfate elongation. 25230886 3 51 theme tumor 370:374 arg1 genes 387:391 tumor suppressor genes 370:391 tumor suppressor genes that encode glycosyltransferases involved in heparan sulfate elongation 370:463 EXT1 and EXT2, are tumor suppressor genes that encode glycosyltransferases involved in heparan sulfate elongation. 25230886 3 51 theme tumor 370:374 arg1 glycosyltransferases 405:424 glycosyltransferases 405:424 glycosyltransferases involved in heparan sulfate elongation 405:463 EXT1 and EXT2, are tumor suppressor genes that encode glycosyltransferases involved in heparan sulfate elongation. 25230886 1 52 theme tumors 252:257 arg1 formation 213:221 the formation 209:221 the formation of multiple cartilage-capped tumors (osteochondromas) 209:275 Multiple osteochondromatosis (MO), or EXT1/EXT2-CDG, is an autosomal dominant O-linked glycosylation disorder characterized by the formation of multiple cartilage-capped tumors (osteochondromas). 24914209 8 0 theme SGT 1085:1087 arg1 activity 1089:1096 SGT activity 1085:1096 SGT activity 1085:1096 Hydroxylation of proline residues adjacent to a serine in acceptor peptides was required for SGT activity. 24914209 12 1 theme glycosyltransferase 1697:1715 arg1 family 1722:1727 a novel glycosyltransferase gene family 1689:1727 a novel glycosyltransferase gene family existing only in the plant kingdom 1689:1762 The SGT1 sequence, which contains a conserved DXD motif and a C-terminal membrane spanning region, is the first example of a glycosyltransferase with type I membrane protein topology, and it showed no homology with known glycosyltransferases, indicating that SGT1 belongs to a novel glycosyltransferase gene family existing only in the plant kingdom. 24914209 6 2 theme cDNA 861:864 arg1 library 866:872 a C. reinhardtii cDNA library 844:872 a C. reinhardtii cDNA library 844:872 The sequence matched the open reading frame XP_001696927 in the C. reinhardtii proteome database, and a corresponding DNA fragment encoding 748 amino acids (BAL63043) was cloned from a C. reinhardtii cDNA library. 24914209 5 3 theme amino 640:644 arg1 sequence 651:658 its amino acid sequence 636:658 its amino acid sequence 636:658 SGT protein was partially purified from cell extracts of C. reinhardtii and analyzed by tandem mass spectrometry to determine its amino acid sequence. 24914209 6 4 theme DNA 779:781 arg1 fragment 783:790 a corresponding DNA fragment 763:790 a corresponding DNA fragment encoding 748 amino acids (BAL63043) 763:826 The sequence matched the open reading frame XP_001696927 in the C. reinhardtii proteome database, and a corresponding DNA fragment encoding 748 amino acids (BAL63043) was cloned from a C. reinhardtii cDNA library. 24914209 6 5 theme C. 846:847 arg1 library 866:872 a C. reinhardtii cDNA library 844:872 a C. reinhardtii cDNA library 844:872 The sequence matched the open reading frame XP_001696927 in the C. reinhardtii proteome database, and a corresponding DNA fragment encoding 748 amino acids (BAL63043) was cloned from a C. reinhardtii cDNA library. 24914209 5 6 theme tandem 598:603 arg1 spectrometry 610:621 tandem mass spectrometry 598:621 tandem mass spectrometry to determine its amino acid sequence 598:658 SGT protein was partially purified from cell extracts of C. reinhardtii and analyzed by tandem mass spectrometry to determine its amino acid sequence. 24914209 12 7 theme known 1629:1633 arg1 glycosyltransferases 1635:1654 known glycosyltransferases 1629:1654 known glycosyltransferases 1629:1654 The SGT1 sequence, which contains a conserved DXD motif and a C-terminal membrane spanning region, is the first example of a glycosyltransferase with type I membrane protein topology, and it showed no homology with known glycosyltransferases, indicating that SGT1 belongs to a novel glycosyltransferase gene family existing only in the plant kingdom. 24914209 1 8 theme O-linked 170:177 arg1 galactose 179:187 O-linked galactose 170:187 O-linked galactose 170:187 In plants, serine residues in extensin, a cell wall protein, are glycosylated with O-linked galactose. 24914209 9 9 theme plant 1169:1173 arg1 genomes 1175:1181 various plant genomes 1161:1181 various plant genomes 1161:1181 Genes for proteins containing conserved domains were found in various plant genomes, including A. thaliana and Nicotiana tabacum. 24914209 12 10 theme first 1520:1524 arg1 sequence 1423:1430 The SGT1 sequence 1414:1430 The SGT1 sequence 1414:1430 The SGT1 sequence, which contains a conserved DXD motif and a C-terminal membrane spanning region, is the first example of a glycosyltransferase with type I membrane protein topology, and it showed no homology with known glycosyltransferases, indicating that SGT1 belongs to a novel glycosyltransferase gene family existing only in the plant kingdom. 24914209 12 10 theme first 1520:1524 arg1 example 1526:1532 the first example 1516:1532 the first example of a glycosyltransferase with type I membrane protein topology 1516:1595 The SGT1 sequence, which contains a conserved DXD motif and a C-terminal membrane spanning region, is the first example of a glycosyltransferase with type I membrane protein topology, and it showed no homology with known glycosyltransferases, indicating that SGT1 belongs to a novel glycosyltransferase gene family existing only in the plant kingdom. 24914209 12 11 theme membrane 1487:1494 arg1 region 1505:1510 a C-terminal membrane spanning region 1474:1510 a C-terminal membrane spanning region 1474:1510 The SGT1 sequence, which contains a conserved DXD motif and a C-terminal membrane spanning region, is the first example of a glycosyltransferase with type I membrane protein topology, and it showed no homology with known glycosyltransferases, indicating that SGT1 belongs to a novel glycosyltransferase gene family existing only in the plant kingdom. 24914209 7 12 theme yeast 932:936 arg1 system 949:954 a yeast expression system 930:954 a yeast expression system 930:954 The 748-amino acid protein (CrSGT1) was produced using a yeast expression system, and the SGT activity was examined. 24914209 1 13 theme wall 134:137 arg1 protein 139:145 a cell wall protein 127:145 a cell wall protein 127:145 In plants, serine residues in extensin, a cell wall protein, are glycosylated with O-linked galactose. 24914209 1 13 theme wall 134:137 arg1 extensin 117:124 extensin 117:124 extensin 117:124 In plants, serine residues in extensin, a cell wall protein, are glycosylated with O-linked galactose. 24914209 9 14 located found 1152:1156 arg2 Genes 1099:1103 Genes 1099:1103 Genes for proteins containing conserved domains 1099:1145 Genes for proteins containing conserved domains were found in various plant genomes, including A. thaliana and Nicotiana tabacum. 24914209 9 14 located found 1152:1156 arg1 genomes 1175:1181 various plant genomes 1161:1181 various plant genomes 1161:1181 Genes for proteins containing conserved domains were found in various plant genomes, including A. thaliana and Nicotiana tabacum. 24914209 0 15 from Identification 0:13 arg1 Plants 79:84 Plants 79:84 Plants 79:84 Identification of Novel Peptidyl Serine α-Galactosyltransferase Gene Family in Plants. 24914209 9 16 theme conserved 1129:1137 arg1 domains 1139:1145 conserved domains 1129:1145 conserved domains 1129:1145 Genes for proteins containing conserved domains were found in various plant genomes, including A. thaliana and Nicotiana tabacum. 24914209 12 17 with homology 1615:1622 arg1 glycosyltransferases 1635:1654 known glycosyltransferases 1629:1654 known glycosyltransferases 1629:1654 The SGT1 sequence, which contains a conserved DXD motif and a C-terminal membrane spanning region, is the first example of a glycosyltransferase with type I membrane protein topology, and it showed no homology with known glycosyltransferases, indicating that SGT1 belongs to a novel glycosyltransferase gene family existing only in the plant kingdom. 24914209 8 18 from serine 1040:1045 arg1 peptides 1059:1066 acceptor peptides 1050:1066 acceptor peptides 1050:1066 Hydroxylation of proline residues adjacent to a serine in acceptor peptides was required for SGT activity. 24914209 3 19 theme serine 314:319 arg1 O-α-galactosyltransferase 321:345 the peptidyl serine O-α-galactosyltransferase 301:345 the peptidyl serine O-α-galactosyltransferase (SGT) 301:351 To identify the peptidyl serine O-α-galactosyltransferase (SGT), we chose Chlamydomonas reinhardtii as a model. 24914209 3 19 theme serine 314:319 arg1 SGT 348:350 SGT 348:350 SGT 348:350 To identify the peptidyl serine O-α-galactosyltransferase (SGT), we chose Chlamydomonas reinhardtii as a model. 24914209 4 20 theme SGT 436:438 arg1 activity 440:447 SGT activity 436:447 SGT activity 436:447 We established an assay system for SGT activity using C. reinhardtii and Arabidopsis thaliana cell extracts. 24914209 11 21 theme NtSGT1 1372:1377 arg1 lines 1363:1367 knockdown lines 1353:1367 knockdown lines of NtSGT1 1353:1377 In addition, knock-out lines of AtSGT1 and knockdown lines of NtSGT1 showed no or reduced SGT activity. 24914209 11 21 theme NtSGT1 1372:1377 arg1 lines 1333:1337 knock-out lines 1323:1337 knock-out lines of AtSGT1 1323:1347 In addition, knock-out lines of AtSGT1 and knockdown lines of NtSGT1 showed no or reduced SGT activity. 24914209 12 22 theme protein 1580:1586 arg1 topology 1588:1595 type I membrane protein topology 1564:1595 type I membrane protein topology 1564:1595 The SGT1 sequence, which contains a conserved DXD motif and a C-terminal membrane spanning region, is the first example of a glycosyltransferase with type I membrane protein topology, and it showed no homology with known glycosyltransferases, indicating that SGT1 belongs to a novel glycosyltransferase gene family existing only in the plant kingdom. 24914209 7 23 theme 748-amino 879:887 arg1 protein 894:900 748-amino acid protein 879:900 The 748-amino acid protein (CrSGT1) 875:909 The 748-amino acid protein (CrSGT1) was produced using a yeast expression system, and the SGT activity was examined. 24914209 7 23 theme 748-amino 879:887 arg1 CrSGT1 903:908 CrSGT1 903:908 CrSGT1 903:908 The 748-amino acid protein (CrSGT1) was produced using a yeast expression system, and the SGT activity was examined. 24914209 11 24 theme reduced 1392:1398 arg1 activity 1404:1411 reduced SGT activity 1392:1411 reduced SGT activity 1392:1411 In addition, knock-out lines of AtSGT1 and knockdown lines of NtSGT1 showed no or reduced SGT activity. 24914209 0 25 theme Novel 18:22 arg1 Family 69:74 Novel Peptidyl Serine α-Galactosyltransferase Gene Family 18:74 Novel Peptidyl Serine α-Galactosyltransferase Gene Family in Plants 18:84 Identification of Novel Peptidyl Serine α-Galactosyltransferase Gene Family in Plants. 24914209 8 26 theme residues 1017:1024 arg1 Hydroxylation 992:1004 Hydroxylation 992:1004 Hydroxylation of proline residues adjacent to a serine in acceptor peptides 992:1066 Hydroxylation of proline residues adjacent to a serine in acceptor peptides was required for SGT activity. 24914209 0 27 theme Serine 33:38 arg1 Family 69:74 Novel Peptidyl Serine α-Galactosyltransferase Gene Family 18:74 Novel Peptidyl Serine α-Galactosyltransferase Gene Family in Plants 18:84 Identification of Novel Peptidyl Serine α-Galactosyltransferase Gene Family in Plants. 24914209 3 28 theme Chlamydomonas 363:375 arg1 reinhardtii 377:387 Chlamydomonas reinhardtii 363:387 Chlamydomonas reinhardtii 363:387 To identify the peptidyl serine O-α-galactosyltransferase (SGT), we chose Chlamydomonas reinhardtii as a model. 24914209 3 28 theme Chlamydomonas 363:375 arg1 model 394:398 a model 392:398 a model 392:398 To identify the peptidyl serine O-α-galactosyltransferase (SGT), we chose Chlamydomonas reinhardtii as a model. 24914209 4 29 theme cell 495:498 arg1 extracts 500:507 cell extracts 495:507 cell extracts 495:507 We established an assay system for SGT activity using C. reinhardtii and Arabidopsis thaliana cell extracts. 24914209 6 30 theme reinhardtii 728:738 arg1 database 749:756 the C. reinhardtii proteome database 721:756 the C. reinhardtii proteome database 721:756 The sequence matched the open reading frame XP_001696927 in the C. reinhardtii proteome database, and a corresponding DNA fragment encoding 748 amino acids (BAL63043) was cloned from a C. reinhardtii cDNA library. 24914209 0 31 theme Gene 64:67 arg1 Family 69:74 Novel Peptidyl Serine α-Galactosyltransferase Gene Family 18:74 Novel Peptidyl Serine α-Galactosyltransferase Gene Family in Plants 18:84 Identification of Novel Peptidyl Serine α-Galactosyltransferase Gene Family in Plants. 24914209 1 32 from residues 105:112 arg1 protein 139:145 a cell wall protein 127:145 a cell wall protein 127:145 In plants, serine residues in extensin, a cell wall protein, are glycosylated with O-linked galactose. 24914209 1 32 from residues 105:112 arg1 extensin 117:124 extensin 117:124 extensin 117:124 In plants, serine residues in extensin, a cell wall protein, are glycosylated with O-linked galactose. 24914209 8 33 theme acceptor 1050:1057 arg1 peptides 1059:1066 acceptor peptides 1050:1066 acceptor peptides 1050:1066 Hydroxylation of proline residues adjacent to a serine in acceptor peptides was required for SGT activity. 24914209 6 34 theme amino 805:809 arg1 acids 811:815 748 amino acids 801:815 748 amino acids (BAL63043) 801:826 The sequence matched the open reading frame XP_001696927 in the C. reinhardtii proteome database, and a corresponding DNA fragment encoding 748 amino acids (BAL63043) was cloned from a C. reinhardtii cDNA library. 24914209 6 34 theme amino 805:809 arg1 BAL63043 818:825 BAL63043 818:825 BAL63043 818:825 The sequence matched the open reading frame XP_001696927 in the C. reinhardtii proteome database, and a corresponding DNA fragment encoding 748 amino acids (BAL63043) was cloned from a C. reinhardtii cDNA library. 24914209 12 35 with glycosyltransferase 1539:1557 arg1 topology 1588:1595 type I membrane protein topology 1564:1595 type I membrane protein topology 1564:1595 The SGT1 sequence, which contains a conserved DXD motif and a C-terminal membrane spanning region, is the first example of a glycosyltransferase with type I membrane protein topology, and it showed no homology with known glycosyltransferases, indicating that SGT1 belongs to a novel glycosyltransferase gene family existing only in the plant kingdom. 24914209 12 36 theme novel 1691:1695 arg1 family 1722:1727 a novel glycosyltransferase gene family 1689:1727 a novel glycosyltransferase gene family existing only in the plant kingdom 1689:1762 The SGT1 sequence, which contains a conserved DXD motif and a C-terminal membrane spanning region, is the first example of a glycosyltransferase with type I membrane protein topology, and it showed no homology with known glycosyltransferases, indicating that SGT1 belongs to a novel glycosyltransferase gene family existing only in the plant kingdom. 24914209 9 37 contain containing 1118:1127 arg1 proteins 1109:1116 proteins 1109:1116 proteins containing conserved domains 1109:1145 Genes for proteins containing conserved domains were found in various plant genomes, including A. thaliana and Nicotiana tabacum. 24914209 9 37 contain containing 1118:1127 arg2 domains 1139:1145 conserved domains 1129:1145 conserved domains 1129:1145 Genes for proteins containing conserved domains were found in various plant genomes, including A. thaliana and Nicotiana tabacum. 24914209 12 38 theme gene 1717:1720 arg1 family 1722:1727 a novel glycosyltransferase gene family 1689:1727 a novel glycosyltransferase gene family existing only in the plant kingdom 1689:1762 The SGT1 sequence, which contains a conserved DXD motif and a C-terminal membrane spanning region, is the first example of a glycosyltransferase with type I membrane protein topology, and it showed no homology with known glycosyltransferases, indicating that SGT1 belongs to a novel glycosyltransferase gene family existing only in the plant kingdom. 24914209 1 39 gly glycosylated 152:163 arg2 residues 105:112 serine residues 98:112 serine residues in extensin, a cell wall protein, 98:146 In plants, serine residues in extensin, a cell wall protein, are glycosylated with O-linked galactose. 24914209 1 39 gly glycosylated 152:163 arg1 plants 90:95 plants 90:95 plants 90:95 In plants, serine residues in extensin, a cell wall protein, are glycosylated with O-linked galactose. 24914209 1 39 gly glycosylated 152:163 arg1 residues 105:112 serine residues 98:112 serine residues in extensin, a cell wall protein, 98:146 In plants, serine residues in extensin, a cell wall protein, are glycosylated with O-linked galactose. 24914209 6 40 theme reading 691:697 arg1 frame 699:703 the open reading frame XP_001696927 682:716 the open reading frame XP_001696927 in the C. reinhardtii proteome database 682:756 The sequence matched the open reading frame XP_001696927 in the C. reinhardtii proteome database, and a corresponding DNA fragment encoding 748 amino acids (BAL63043) was cloned from a C. reinhardtii cDNA library. 24914209 11 41 theme AtSGT1 1342:1347 arg1 lines 1363:1367 knockdown lines 1353:1367 knockdown lines of NtSGT1 1353:1377 In addition, knock-out lines of AtSGT1 and knockdown lines of NtSGT1 showed no or reduced SGT activity. 24914209 11 41 theme AtSGT1 1342:1347 arg1 lines 1333:1337 knock-out lines 1323:1337 knock-out lines of AtSGT1 1323:1347 In addition, knock-out lines of AtSGT1 and knockdown lines of NtSGT1 showed no or reduced SGT activity. 24914209 6 42 theme reinhardtii 849:859 arg1 library 866:872 a C. reinhardtii cDNA library 844:872 a C. reinhardtii cDNA library 844:872 The sequence matched the open reading frame XP_001696927 in the C. reinhardtii proteome database, and a corresponding DNA fragment encoding 748 amino acids (BAL63043) was cloned from a C. reinhardtii cDNA library. 24914209 6 43 theme corresponding 765:777 arg1 fragment 783:790 a corresponding DNA fragment 763:790 a corresponding DNA fragment encoding 748 amino acids (BAL63043) 763:826 The sequence matched the open reading frame XP_001696927 in the C. reinhardtii proteome database, and a corresponding DNA fragment encoding 748 amino acids (BAL63043) was cloned from a C. reinhardtii cDNA library. 24914209 2 44 theme serine 253:258 arg1 galactosylation 234:248 the galactosylation 230:248 the galactosylation of serine 230:258 However, the enzyme that is involved in the galactosylation of serine had not yet been identified. 24914209 5 45 theme mass 605:608 arg1 spectrometry 610:621 tandem mass spectrometry 598:621 tandem mass spectrometry to determine its amino acid sequence 598:658 SGT protein was partially purified from cell extracts of C. reinhardtii and analyzed by tandem mass spectrometry to determine its amino acid sequence. 24914209 9 46 theme various 1161:1167 arg1 genomes 1175:1181 various plant genomes 1161:1181 various plant genomes 1161:1181 Genes for proteins containing conserved domains were found in various plant genomes, including A. thaliana and Nicotiana tabacum. 24914209 6 47 theme C. 725:726 arg1 database 749:756 the C. reinhardtii proteome database 721:756 the C. reinhardtii proteome database 721:756 The sequence matched the open reading frame XP_001696927 in the C. reinhardtii proteome database, and a corresponding DNA fragment encoding 748 amino acids (BAL63043) was cloned from a C. reinhardtii cDNA library. 24914209 4 48 theme assay 419:423 arg1 system 425:430 an assay system 416:430 an assay system for SGT activity 416:447 We established an assay system for SGT activity using C. reinhardtii and Arabidopsis thaliana cell extracts. 24914209 12 49 theme spanning 1496:1503 arg1 region 1505:1510 a C-terminal membrane spanning region 1474:1510 a C-terminal membrane spanning region 1474:1510 The SGT1 sequence, which contains a conserved DXD motif and a C-terminal membrane spanning region, is the first example of a glycosyltransferase with type I membrane protein topology, and it showed no homology with known glycosyltransferases, indicating that SGT1 belongs to a novel glycosyltransferase gene family existing only in the plant kingdom. 24914209 0 50 from Plants 79:84 arg1 Identification 0:13 Identification 0:13 Identification of Novel Peptidyl Serine α-Galactosyltransferase Gene Family in Plants. 0:85 Identification of Novel Peptidyl Serine α-Galactosyltransferase Gene Family in Plants. 24914209 5 51 theme acid 646:649 arg1 sequence 651:658 its amino acid sequence 636:658 its amino acid sequence 636:658 SGT protein was partially purified from cell extracts of C. reinhardtii and analyzed by tandem mass spectrometry to determine its amino acid sequence. 24914209 7 52 theme SGT 965:967 arg1 activity 969:976 the SGT activity 961:976 the SGT activity 961:976 The 748-amino acid protein (CrSGT1) was produced using a yeast expression system, and the SGT activity was examined. 24914209 11 53 theme SGT 1400:1402 arg1 activity 1404:1411 reduced SGT activity 1392:1411 reduced SGT activity 1392:1411 In addition, knock-out lines of AtSGT1 and knockdown lines of NtSGT1 showed no or reduced SGT activity. 24914209 9 54 theme Nicotiana 1210:1218 arg1 tabacum 1220:1226 Nicotiana tabacum 1210:1226 Nicotiana tabacum 1210:1226 Genes for proteins containing conserved domains were found in various plant genomes, including A. thaliana and Nicotiana tabacum. 24914209 7 55 theme expression 938:947 arg1 system 949:954 a yeast expression system 930:954 a yeast expression system 930:954 The 748-amino acid protein (CrSGT1) was produced using a yeast expression system, and the SGT activity was examined. 24914209 1 56 theme cell 129:132 arg1 protein 139:145 a cell wall protein 127:145 a cell wall protein 127:145 In plants, serine residues in extensin, a cell wall protein, are glycosylated with O-linked galactose. 24914209 1 56 theme cell 129:132 arg1 extensin 117:124 extensin 117:124 extensin 117:124 In plants, serine residues in extensin, a cell wall protein, are glycosylated with O-linked galactose. 24914209 12 57 theme C-terminal 1476:1485 arg1 region 1505:1510 a C-terminal membrane spanning region 1474:1510 a C-terminal membrane spanning region 1474:1510 The SGT1 sequence, which contains a conserved DXD motif and a C-terminal membrane spanning region, is the first example of a glycosyltransferase with type I membrane protein topology, and it showed no homology with known glycosyltransferases, indicating that SGT1 belongs to a novel glycosyltransferase gene family existing only in the plant kingdom. 24914209 3 58 theme peptidyl 305:312 arg1 O-α-galactosyltransferase 321:345 the peptidyl serine O-α-galactosyltransferase 301:345 the peptidyl serine O-α-galactosyltransferase (SGT) 301:351 To identify the peptidyl serine O-α-galactosyltransferase (SGT), we chose Chlamydomonas reinhardtii as a model. 24914209 3 58 theme peptidyl 305:312 arg1 SGT 348:350 SGT 348:350 SGT 348:350 To identify the peptidyl serine O-α-galactosyltransferase (SGT), we chose Chlamydomonas reinhardtii as a model. 24914209 5 59 theme SGT 510:512 arg1 protein 514:520 SGT protein 510:520 SGT protein 510:520 SGT protein was partially purified from cell extracts of C. reinhardtii and analyzed by tandem mass spectrometry to determine its amino acid sequence. 24914209 5 60 theme reinhardtii 570:580 arg1 extracts 555:562 cell extracts 550:562 cell extracts of C. reinhardtii 550:580 SGT protein was partially purified from cell extracts of C. reinhardtii and analyzed by tandem mass spectrometry to determine its amino acid sequence. 24914209 12 61 theme DXD 1460:1462 arg1 motif 1464:1468 a conserved DXD motif 1448:1468 a conserved DXD motif 1448:1468 The SGT1 sequence, which contains a conserved DXD motif and a C-terminal membrane spanning region, is the first example of a glycosyltransferase with type I membrane protein topology, and it showed no homology with known glycosyltransferases, indicating that SGT1 belongs to a novel glycosyltransferase gene family existing only in the plant kingdom. 24914209 0 62 from Family 69:74 arg1 Plants 79:84 Plants 79:84 Plants 79:84 Identification of Novel Peptidyl Serine α-Galactosyltransferase Gene Family in Plants. 24914209 6 63 theme open 686:689 arg1 frame 699:703 the open reading frame XP_001696927 682:716 the open reading frame XP_001696927 in the C. reinhardtii proteome database 682:756 The sequence matched the open reading frame XP_001696927 in the C. reinhardtii proteome database, and a corresponding DNA fragment encoding 748 amino acids (BAL63043) was cloned from a C. reinhardtii cDNA library. 24914209 10 64 theme AtSGT1 1233:1238 arg1 proteins 1251:1258 The AtSGT1 and NtSGT1 proteins 1229:1258 The AtSGT1 and NtSGT1 proteins 1229:1258 The AtSGT1 and NtSGT1 proteins also showed SGT activity when expressed in yeast. 24914209 12 65 theme type 1564:1567 arg1 topology 1588:1595 type I membrane protein topology 1564:1595 type I membrane protein topology 1564:1595 The SGT1 sequence, which contains a conserved DXD motif and a C-terminal membrane spanning region, is the first example of a glycosyltransferase with type I membrane protein topology, and it showed no homology with known glycosyltransferases, indicating that SGT1 belongs to a novel glycosyltransferase gene family existing only in the plant kingdom. 24914209 12 66 theme conserved 1450:1458 arg1 motif 1464:1468 a conserved DXD motif 1448:1468 a conserved DXD motif 1448:1468 The SGT1 sequence, which contains a conserved DXD motif and a C-terminal membrane spanning region, is the first example of a glycosyltransferase with type I membrane protein topology, and it showed no homology with known glycosyltransferases, indicating that SGT1 belongs to a novel glycosyltransferase gene family existing only in the plant kingdom. 24914209 1 67 link O-linked 170:177 arg1 galactose 179:187 O-linked galactose 170:187 O-linked galactose 170:187 In plants, serine residues in extensin, a cell wall protein, are glycosylated with O-linked galactose. 24914209 11 68 theme knockdown 1353:1361 arg1 lines 1363:1367 knockdown lines 1353:1367 knockdown lines of NtSGT1 1353:1377 In addition, knock-out lines of AtSGT1 and knockdown lines of NtSGT1 showed no or reduced SGT activity. 24914209 8 69 theme proline 1009:1015 arg1 residues 1017:1024 proline residues 1009:1024 proline residues adjacent to a serine in acceptor peptides 1009:1066 Hydroxylation of proline residues adjacent to a serine in acceptor peptides was required for SGT activity. 24914209 5 70 theme cell 550:553 arg1 extracts 555:562 cell extracts 550:562 cell extracts of C. reinhardtii 550:580 SGT protein was partially purified from cell extracts of C. reinhardtii and analyzed by tandem mass spectrometry to determine its amino acid sequence. 24914209 12 71 theme membrane 1571:1578 arg1 topology 1588:1595 type I membrane protein topology 1564:1595 type I membrane protein topology 1564:1595 The SGT1 sequence, which contains a conserved DXD motif and a C-terminal membrane spanning region, is the first example of a glycosyltransferase with type I membrane protein topology, and it showed no homology with known glycosyltransferases, indicating that SGT1 belongs to a novel glycosyltransferase gene family existing only in the plant kingdom. 24914209 0 72 theme Peptidyl 24:31 arg1 Family 69:74 Novel Peptidyl Serine α-Galactosyltransferase Gene Family 18:74 Novel Peptidyl Serine α-Galactosyltransferase Gene Family in Plants 18:84 Identification of Novel Peptidyl Serine α-Galactosyltransferase Gene Family in Plants. 24914209 8 73 theme adjacent 1026:1033 arg1 residues 1017:1024 proline residues 1009:1024 proline residues adjacent to a serine in acceptor peptides 1009:1066 Hydroxylation of proline residues adjacent to a serine in acceptor peptides was required for SGT activity. 24914209 7 74 theme acid 889:892 arg1 protein 894:900 748-amino acid protein 879:900 The 748-amino acid protein (CrSGT1) 875:909 The 748-amino acid protein (CrSGT1) was produced using a yeast expression system, and the SGT activity was examined. 24914209 7 74 theme acid 889:892 arg1 CrSGT1 903:908 CrSGT1 903:908 CrSGT1 903:908 The 748-amino acid protein (CrSGT1) was produced using a yeast expression system, and the SGT activity was examined. 24914209 1 75 theme serine 98:103 arg1 residues 105:112 serine residues 98:112 serine residues in extensin, a cell wall protein, 98:146 In plants, serine residues in extensin, a cell wall protein, are glycosylated with O-linked galactose. 24914209 10 76 theme NtSGT1 1244:1249 arg1 proteins 1251:1258 The AtSGT1 and NtSGT1 proteins 1229:1258 The AtSGT1 and NtSGT1 proteins 1229:1258 The AtSGT1 and NtSGT1 proteins also showed SGT activity when expressed in yeast. 24914209 0 77 theme α-Galactosyltransferase 40:62 arg1 Family 69:74 Novel Peptidyl Serine α-Galactosyltransferase Gene Family 18:74 Novel Peptidyl Serine α-Galactosyltransferase Gene Family in Plants 18:84 Identification of Novel Peptidyl Serine α-Galactosyltransferase Gene Family in Plants. 24914209 12 78 theme SGT1 1418:1421 arg1 sequence 1423:1430 The SGT1 sequence 1414:1430 The SGT1 sequence 1414:1430 The SGT1 sequence, which contains a conserved DXD motif and a C-terminal membrane spanning region, is the first example of a glycosyltransferase with type I membrane protein topology, and it showed no homology with known glycosyltransferases, indicating that SGT1 belongs to a novel glycosyltransferase gene family existing only in the plant kingdom. 24914209 12 78 theme SGT1 1418:1421 arg1 example 1526:1532 the first example 1516:1532 the first example of a glycosyltransferase with type I membrane protein topology 1516:1595 The SGT1 sequence, which contains a conserved DXD motif and a C-terminal membrane spanning region, is the first example of a glycosyltransferase with type I membrane protein topology, and it showed no homology with known glycosyltransferases, indicating that SGT1 belongs to a novel glycosyltransferase gene family existing only in the plant kingdom. 24914209 12 79 theme glycosyltransferase 1539:1557 arg1 sequence 1423:1430 The SGT1 sequence 1414:1430 The SGT1 sequence 1414:1430 The SGT1 sequence, which contains a conserved DXD motif and a C-terminal membrane spanning region, is the first example of a glycosyltransferase with type I membrane protein topology, and it showed no homology with known glycosyltransferases, indicating that SGT1 belongs to a novel glycosyltransferase gene family existing only in the plant kingdom. 24914209 12 79 theme glycosyltransferase 1539:1557 arg1 example 1526:1532 the first example 1516:1532 the first example of a glycosyltransferase with type I membrane protein topology 1516:1595 The SGT1 sequence, which contains a conserved DXD motif and a C-terminal membrane spanning region, is the first example of a glycosyltransferase with type I membrane protein topology, and it showed no homology with known glycosyltransferases, indicating that SGT1 belongs to a novel glycosyltransferase gene family existing only in the plant kingdom. 24914209 6 80 theme proteome 740:747 arg1 database 749:756 the C. reinhardtii proteome database 721:756 the C. reinhardtii proteome database 721:756 The sequence matched the open reading frame XP_001696927 in the C. reinhardtii proteome database, and a corresponding DNA fragment encoding 748 amino acids (BAL63043) was cloned from a C. reinhardtii cDNA library. 24914209 0 81 theme Family 69:74 arg1 Identification 0:13 Identification 0:13 Identification of Novel Peptidyl Serine α-Galactosyltransferase Gene Family in Plants. 0:85 Identification of Novel Peptidyl Serine α-Galactosyltransferase Gene Family in Plants. 24914209 12 82 theme plant 1750:1754 arg1 kingdom 1756:1762 the plant kingdom 1746:1762 the plant kingdom 1746:1762 The SGT1 sequence, which contains a conserved DXD motif and a C-terminal membrane spanning region, is the first example of a glycosyltransferase with type I membrane protein topology, and it showed no homology with known glycosyltransferases, indicating that SGT1 belongs to a novel glycosyltransferase gene family existing only in the plant kingdom. 24914209 10 83 theme SGT 1272:1274 arg1 activity 1276:1283 SGT activity 1272:1283 SGT activity 1272:1283 The AtSGT1 and NtSGT1 proteins also showed SGT activity when expressed in yeast. 24914209 4 84 dep reinhardtii 458:468 arg1 extracts 500:507 cell extracts 495:507 cell extracts 495:507 We established an assay system for SGT activity using C. reinhardtii and Arabidopsis thaliana cell extracts. 24914209 6 85 theme 748 801:803 arg1 acids 811:815 748 amino acids 801:815 748 amino acids (BAL63043) 801:826 The sequence matched the open reading frame XP_001696927 in the C. reinhardtii proteome database, and a corresponding DNA fragment encoding 748 amino acids (BAL63043) was cloned from a C. reinhardtii cDNA library. 24914209 6 85 theme 748 801:803 arg1 BAL63043 818:825 BAL63043 818:825 BAL63043 818:825 The sequence matched the open reading frame XP_001696927 in the C. reinhardtii proteome database, and a corresponding DNA fragment encoding 748 amino acids (BAL63043) was cloned from a C. reinhardtii cDNA library. 24914209 6 86 from frame 699:703 arg1 database 749:756 the C. reinhardtii proteome database 721:756 the C. reinhardtii proteome database 721:756 The sequence matched the open reading frame XP_001696927 in the C. reinhardtii proteome database, and a corresponding DNA fragment encoding 748 amino acids (BAL63043) was cloned from a C. reinhardtii cDNA library. 24914209 12 87 contain contains 1439:1446 arg1 sequence 1423:1430 The SGT1 sequence 1414:1430 The SGT1 sequence 1414:1430 The SGT1 sequence, which contains a conserved DXD motif and a C-terminal membrane spanning region, is the first example of a glycosyltransferase with type I membrane protein topology, and it showed no homology with known glycosyltransferases, indicating that SGT1 belongs to a novel glycosyltransferase gene family existing only in the plant kingdom. 24914209 12 87 contain contains 1439:1446 arg1 example 1526:1532 the first example 1516:1532 the first example of a glycosyltransferase with type I membrane protein topology 1516:1595 The SGT1 sequence, which contains a conserved DXD motif and a C-terminal membrane spanning region, is the first example of a glycosyltransferase with type I membrane protein topology, and it showed no homology with known glycosyltransferases, indicating that SGT1 belongs to a novel glycosyltransferase gene family existing only in the plant kingdom. 24914209 12 87 contain contains 1439:1446 arg2 motif 1464:1468 a conserved DXD motif 1448:1468 a conserved DXD motif 1448:1468 The SGT1 sequence, which contains a conserved DXD motif and a C-terminal membrane spanning region, is the first example of a glycosyltransferase with type I membrane protein topology, and it showed no homology with known glycosyltransferases, indicating that SGT1 belongs to a novel glycosyltransferase gene family existing only in the plant kingdom. 24914209 12 87 contain contains 1439:1446 arg2 region 1505:1510 a C-terminal membrane spanning region 1474:1510 a C-terminal membrane spanning region 1474:1510 The SGT1 sequence, which contains a conserved DXD motif and a C-terminal membrane spanning region, is the first example of a glycosyltransferase with type I membrane protein topology, and it showed no homology with known glycosyltransferases, indicating that SGT1 belongs to a novel glycosyltransferase gene family existing only in the plant kingdom. 24914209 11 88 theme knock-out 1323:1331 arg1 lines 1333:1337 knock-out lines 1323:1337 knock-out lines of AtSGT1 1323:1347 In addition, knock-out lines of AtSGT1 and knockdown lines of NtSGT1 showed no or reduced SGT activity. 26206337 9 0 theme mutated 1774:1780 arg1 RTKs 1782:1785 mutated RTKs 1774:1785 mutated RTKs 1774:1785 In conclusion, 2-DG displays a significant antileukemic activity in AML with FLT3-ITD or KIT mutations, opening a new therapeutic window in a subset of AML with mutated RTKs. 26206337 3 1 theme mutated 645:651 arg1 c-KIT 653:657 mutated c-KIT 645:657 mutated c-KIT 645:657 2-DG, through N-linked glycosylation inhibition, affected the cell-surface expression and cellular signaling of both FTL3-ITD and mutated c-KIT and induced apoptotic cell death. 26206337 1 2 theme kinases 272:278 arg1 expression 240:249 expression 240:249 expression of receptor tyrosine kinases (RTK) commonly mutated in acute myeloid leukemia (AML) 240:333 We assessed the antileukemic activity of 2-deoxy-d-glucose (2-DG) through the modulation of expression of receptor tyrosine kinases (RTK) commonly mutated in acute myeloid leukemia (AML). 26206337 4 3 theme 2-DG 814:817 arg1 treatment 819:827 2-DG treatment 814:827 2-DG treatment 814:827 Leukemic cells harboring these mutated RTKs (MV4-11, MOLM-14, Kasumi-1, and TF-1 c-KIT D816V) were the most sensitive to 2-DG treatment in vitro as compared with nonmutated cells. 26206337 8 4 from expression 1476:1485 arg1 cells 1494:1498 AML cells 1490:1498 AML cells 1490:1498 Finally, we showed that 2-DG decreases Mcl-1 protein expression in AML cells and induces sensitization to both the BH3 mimetic inhibitor of Bcl-xL, Bcl-2 and Bcl-w, ABT-737, and cytarabine. 26206337 7 5 theme in 1358:1359 arg1 effect 1366:1371 a strong in vivo effect 1349:1371 a strong in vivo effect in NOD/SCID mice xenografted with Kasumi-1 cells 1349:1420 In these cells, 2-DG inhibited the cell-surface expression of c-KIT, abrogated STAT3 and MAPK-ERK pathways, and strongly downregulated the expression of the receptor resulting in a strong in vivo effect in NOD/SCID mice xenografted with Kasumi-1 cells. 26206337 3 6 theme apoptotic 671:679 arg1 death 686:690 apoptotic cell death 671:690 apoptotic cell death 671:690 2-DG, through N-linked glycosylation inhibition, affected the cell-surface expression and cellular signaling of both FTL3-ITD and mutated c-KIT and induced apoptotic cell death. 26206337 1 7 theme 2-deoxy-d-glucose 189:205 arg1 activity 177:184 the antileukemic activity 160:184 the antileukemic activity of 2-deoxy-d-glucose (2-DG) 160:212 We assessed the antileukemic activity of 2-deoxy-d-glucose (2-DG) through the modulation of expression of receptor tyrosine kinases (RTK) commonly mutated in acute myeloid leukemia (AML). 26206337 6 8 theme cell 1103:1106 arg1 lines 1108:1112 c-KIT-mutated cell lines 1089:1112 c-KIT-mutated cell lines 1089:1112 Moreover, the antileukemic activity of 2-DG was particularly marked in c-KIT-mutated cell lines and cell samples from core binding factor-AML patients. 26206337 2 9 theme growth 496:501 arg1 inhibition 503:512 tumor cell growth inhibition 485:512 tumor cell growth inhibition 485:512 We used human leukemic cell lines cells, both in vitro and in vivo, as well as leukemic samples from AML patients to demonstrate the role of 2-DG in tumor cell growth inhibition. 26206337 0 10 theme c-KIT 131:135 arg1 Mutations 137:145 FLT3-ITD or c-KIT Mutations 119:145 FLT3-ITD or c-KIT Mutations 119:145 Antileukemic Activity of 2-Deoxy-d-Glucose through Inhibition of N-Linked Glycosylation in Acute Myeloid Leukemia with FLT3-ITD or c-KIT Mutations. 26206337 2 11 theme tumor 485:489 arg1 growth 496:501 tumor cell growth 485:501 tumor cell growth inhibition 485:512 We used human leukemic cell lines cells, both in vitro and in vivo, as well as leukemic samples from AML patients to demonstrate the role of 2-DG in tumor cell growth inhibition. 26206337 5 12 theme kinase 982:987 arg1 quizartinib 1005:1015 the tyrosine kinase inhibitor (TKI) quizartinib 969:1015 the tyrosine kinase inhibitor (TKI) quizartinib 969:1015 2-DG activity was also demonstrated in leukemic cells harboring FLT3-TKD mutations resistant to the tyrosine kinase inhibitor (TKI) quizartinib. 26206337 3 13 theme N-linked 529:536 arg1 glycosylation 538:550 N-linked glycosylation 529:550 N-linked glycosylation inhibition 529:561 2-DG, through N-linked glycosylation inhibition, affected the cell-surface expression and cellular signaling of both FTL3-ITD and mutated c-KIT and induced apoptotic cell death. 26206337 6 14 theme factor-AML 1149:1158 arg1 patients 1160:1167 core binding factor-AML patients 1136:1167 core binding factor-AML patients 1136:1167 Moreover, the antileukemic activity of 2-DG was particularly marked in c-KIT-mutated cell lines and cell samples from core binding factor-AML patients. 26206337 6 15 from patients 1160:1167 arg1 lines 1108:1112 c-KIT-mutated cell lines 1089:1112 c-KIT-mutated cell lines 1089:1112 Moreover, the antileukemic activity of 2-DG was particularly marked in c-KIT-mutated cell lines and cell samples from core binding factor-AML patients. 26206337 6 15 from patients 1160:1167 arg1 samples 1123:1129 cell samples 1118:1129 cell samples from core binding factor-AML patients 1118:1167 Moreover, the antileukemic activity of 2-DG was particularly marked in c-KIT-mutated cell lines and cell samples from core binding factor-AML patients. 26206337 3 16 theme cell-surface 577:588 arg1 expression 590:599 cell-surface expression 577:599 cell-surface expression 577:599 2-DG, through N-linked glycosylation inhibition, affected the cell-surface expression and cellular signaling of both FTL3-ITD and mutated c-KIT and induced apoptotic cell death. 26206337 9 17 theme antileukemic 1656:1667 arg1 activity 1669:1676 a significant antileukemic activity 1642:1676 a significant antileukemic activity in AML 1642:1683 In conclusion, 2-DG displays a significant antileukemic activity in AML with FLT3-ITD or KIT mutations, opening a new therapeutic window in a subset of AML with mutated RTKs. 26206337 6 18 theme core 1136:1139 arg1 patients 1160:1167 core binding factor-AML patients 1136:1167 core binding factor-AML patients 1136:1167 Moreover, the antileukemic activity of 2-DG was particularly marked in c-KIT-mutated cell lines and cell samples from core binding factor-AML patients. 26206337 0 19 theme Glycosylation 74:86 arg1 Inhibition 51:60 Inhibition 51:60 Inhibition of N-Linked Glycosylation in Acute Myeloid Leukemia with FLT3-ITD or c-KIT Mutations 51:145 Antileukemic Activity of 2-Deoxy-d-Glucose through Inhibition of N-Linked Glycosylation in Acute Myeloid Leukemia with FLT3-ITD or c-KIT Mutations. 26206337 0 20 theme Acute 91:95 arg1 Leukemia 105:112 Acute Myeloid Leukemia 91:112 Acute Myeloid Leukemia with FLT3-ITD or c-KIT Mutations 91:145 Antileukemic Activity of 2-Deoxy-d-Glucose through Inhibition of N-Linked Glycosylation in Acute Myeloid Leukemia with FLT3-ITD or c-KIT Mutations. 26206337 7 21 from effect 1366:1371 arg1 mice 1385:1388 NOD/SCID mice 1376:1388 NOD/SCID mice xenografted with Kasumi-1 cells 1376:1420 In these cells, 2-DG inhibited the cell-surface expression of c-KIT, abrogated STAT3 and MAPK-ERK pathways, and strongly downregulated the expression of the receptor resulting in a strong in vivo effect in NOD/SCID mice xenografted with Kasumi-1 cells. 26206337 2 22 theme 2-DG 477:480 arg1 role 469:472 the role 465:472 the role of 2-DG in tumor cell growth inhibition 465:512 We used human leukemic cell lines cells, both in vitro and in vivo, as well as leukemic samples from AML patients to demonstrate the role of 2-DG in tumor cell growth inhibition. 26206337 6 23 theme cell 1118:1121 arg1 samples 1123:1129 cell samples 1118:1129 cell samples from core binding factor-AML patients 1118:1167 Moreover, the antileukemic activity of 2-DG was particularly marked in c-KIT-mutated cell lines and cell samples from core binding factor-AML patients. 26206337 6 24 from lines 1108:1112 arg1 marked 1079:1084 marked 1079:1084 marked 1079:1084 Moreover, the antileukemic activity of 2-DG was particularly marked in c-KIT-mutated cell lines and cell samples from core binding factor-AML patients. 26206337 6 24 from lines 1108:1112 arg1 activity 1045:1052 the antileukemic activity 1028:1052 the antileukemic activity of 2-DG 1028:1060 Moreover, the antileukemic activity of 2-DG was particularly marked in c-KIT-mutated cell lines and cell samples from core binding factor-AML patients. 26206337 0 25 theme FLT3-ITD 119:126 arg1 Mutations 137:145 FLT3-ITD or c-KIT Mutations 119:145 FLT3-ITD or c-KIT Mutations 119:145 Antileukemic Activity of 2-Deoxy-d-Glucose through Inhibition of N-Linked Glycosylation in Acute Myeloid Leukemia with FLT3-ITD or c-KIT Mutations. 26206337 5 26 theme leukemic 912:919 arg1 cells 921:925 leukemic cells 912:925 leukemic cells harboring FLT3-TKD mutations resistant to the tyrosine kinase inhibitor (TKI) quizartinib 912:1015 2-DG activity was also demonstrated in leukemic cells harboring FLT3-TKD mutations resistant to the tyrosine kinase inhibitor (TKI) quizartinib. 26206337 8 27 theme Mcl-1 1462:1466 arg1 expression 1476:1485 Mcl-1 protein expression 1462:1485 Mcl-1 protein expression in AML cells 1462:1498 Finally, we showed that 2-DG decreases Mcl-1 protein expression in AML cells and induces sensitization to both the BH3 mimetic inhibitor of Bcl-xL, Bcl-2 and Bcl-w, ABT-737, and cytarabine. 26206337 0 28 theme Antileukemic 0:11 arg1 Activity 13:20 Antileukemic Activity 0:20 Antileukemic Activity of 2-Deoxy-d-Glucose through Inhibition of N-Linked Glycosylation in Acute Myeloid Leukemia with FLT3-ITD or c-KIT Mutations. 0:146 Antileukemic Activity of 2-Deoxy-d-Glucose through Inhibition of N-Linked Glycosylation in Acute Myeloid Leukemia with FLT3-ITD or c-KIT Mutations. 26206337 5 29 theme 2-DG 873:876 arg1 activity 878:885 2-DG activity 873:885 2-DG activity 873:885 2-DG activity was also demonstrated in leukemic cells harboring FLT3-TKD mutations resistant to the tyrosine kinase inhibitor (TKI) quizartinib. 26206337 7 30 theme MAPK-ERK 1259:1266 arg1 pathways 1268:1275 MAPK-ERK pathways 1259:1275 MAPK-ERK pathways 1259:1275 In these cells, 2-DG inhibited the cell-surface expression of c-KIT, abrogated STAT3 and MAPK-ERK pathways, and strongly downregulated the expression of the receptor resulting in a strong in vivo effect in NOD/SCID mice xenografted with Kasumi-1 cells. 26206337 6 31 from marked 1079:1084 arg1 lines 1108:1112 c-KIT-mutated cell lines 1089:1112 c-KIT-mutated cell lines 1089:1112 Moreover, the antileukemic activity of 2-DG was particularly marked in c-KIT-mutated cell lines and cell samples from core binding factor-AML patients. 26206337 6 31 from marked 1079:1084 arg1 samples 1123:1129 cell samples 1118:1129 cell samples from core binding factor-AML patients 1118:1167 Moreover, the antileukemic activity of 2-DG was particularly marked in c-KIT-mutated cell lines and cell samples from core binding factor-AML patients. 26206337 9 32 theme new 1727:1729 arg1 window 1743:1748 a new therapeutic window 1725:1748 a new therapeutic window in a subset of AML with mutated RTKs 1725:1785 In conclusion, 2-DG displays a significant antileukemic activity in AML with FLT3-ITD or KIT mutations, opening a new therapeutic window in a subset of AML with mutated RTKs. 26206337 8 33 theme AML 1490:1492 arg1 cells 1494:1498 AML cells 1490:1498 AML cells 1490:1498 Finally, we showed that 2-DG decreases Mcl-1 protein expression in AML cells and induces sensitization to both the BH3 mimetic inhibitor of Bcl-xL, Bcl-2 and Bcl-w, ABT-737, and cytarabine. 26206337 1 34 theme acute 306:310 arg1 AML 330:332 AML 330:332 AML 330:332 We assessed the antileukemic activity of 2-deoxy-d-glucose (2-DG) through the modulation of expression of receptor tyrosine kinases (RTK) commonly mutated in acute myeloid leukemia (AML). 26206337 1 34 theme acute 306:310 arg1 leukemia 320:327 acute myeloid leukemia 306:327 acute myeloid leukemia (AML) 306:333 We assessed the antileukemic activity of 2-deoxy-d-glucose (2-DG) through the modulation of expression of receptor tyrosine kinases (RTK) commonly mutated in acute myeloid leukemia (AML). 26206337 9 35 theme therapeutic 1731:1741 arg1 window 1743:1748 a new therapeutic window 1725:1748 a new therapeutic window in a subset of AML with mutated RTKs 1725:1785 In conclusion, 2-DG displays a significant antileukemic activity in AML with FLT3-ITD or KIT mutations, opening a new therapeutic window in a subset of AML with mutated RTKs. 26206337 2 36 theme leukemic 415:422 arg1 samples 424:430 leukemic samples 415:430 leukemic samples from AML patients 415:448 We used human leukemic cell lines cells, both in vitro and in vivo, as well as leukemic samples from AML patients to demonstrate the role of 2-DG in tumor cell growth inhibition. 26206337 4 37 theme c-KIT 774:778 arg1 RTKs 732:735 these mutated RTKs 718:735 these mutated RTKs (MV4-11, MOLM-14, Kasumi-1, and TF-1 c-KIT D816V) 718:785 Leukemic cells harboring these mutated RTKs (MV4-11, MOLM-14, Kasumi-1, and TF-1 c-KIT D816V) were the most sensitive to 2-DG treatment in vitro as compared with nonmutated cells. 26206337 4 37 theme c-KIT 774:778 arg1 D816V 780:784 TF-1 c-KIT D816V 769:784 TF-1 c-KIT D816V 769:784 Leukemic cells harboring these mutated RTKs (MV4-11, MOLM-14, Kasumi-1, and TF-1 c-KIT D816V) were the most sensitive to 2-DG treatment in vitro as compared with nonmutated cells. 26206337 5 38 theme tyrosine 973:980 arg1 quizartinib 1005:1015 the tyrosine kinase inhibitor (TKI) quizartinib 969:1015 the tyrosine kinase inhibitor (TKI) quizartinib 969:1015 2-DG activity was also demonstrated in leukemic cells harboring FLT3-TKD mutations resistant to the tyrosine kinase inhibitor (TKI) quizartinib. 26206337 8 39 theme Bcl-2 1571:1575 arg1 ABT-737 1588:1594 ABT-737 1588:1594 ABT-737 1588:1594 Finally, we showed that 2-DG decreases Mcl-1 protein expression in AML cells and induces sensitization to both the BH3 mimetic inhibitor of Bcl-xL, Bcl-2 and Bcl-w, ABT-737, and cytarabine. 26206337 8 39 theme Bcl-2 1571:1575 arg1 inhibitor 1550:1558 the BH3 mimetic inhibitor 1534:1558 the BH3 mimetic inhibitor of Bcl-xL, Bcl-2 and Bcl-w 1534:1585 Finally, we showed that 2-DG decreases Mcl-1 protein expression in AML cells and induces sensitization to both the BH3 mimetic inhibitor of Bcl-xL, Bcl-2 and Bcl-w, ABT-737, and cytarabine. 26206337 8 39 theme Bcl-2 1571:1575 arg1 cytarabine 1601:1610 cytarabine 1601:1610 cytarabine 1601:1610 Finally, we showed that 2-DG decreases Mcl-1 protein expression in AML cells and induces sensitization to both the BH3 mimetic inhibitor of Bcl-xL, Bcl-2 and Bcl-w, ABT-737, and cytarabine. 26206337 3 40 dep expression 590:599 arg1 the 573:575 the 573:575 the 573:575 2-DG, through N-linked glycosylation inhibition, affected the cell-surface expression and cellular signaling of both FTL3-ITD and mutated c-KIT and induced apoptotic cell death. 26206337 7 41 theme cell-surface 1205:1216 arg1 expression 1218:1227 the cell-surface expression 1201:1227 the cell-surface expression of c-KIT 1201:1236 In these cells, 2-DG inhibited the cell-surface expression of c-KIT, abrogated STAT3 and MAPK-ERK pathways, and strongly downregulated the expression of the receptor resulting in a strong in vivo effect in NOD/SCID mice xenografted with Kasumi-1 cells. 26206337 2 42 theme cell 359:362 arg1 lines 364:368 human leukemic cell lines 344:368 human leukemic cell lines cells 344:374 We used human leukemic cell lines cells, both in vitro and in vivo, as well as leukemic samples from AML patients to demonstrate the role of 2-DG in tumor cell growth inhibition. 26206337 8 43 theme Bcl-w 1581:1585 arg1 ABT-737 1588:1594 ABT-737 1588:1594 ABT-737 1588:1594 Finally, we showed that 2-DG decreases Mcl-1 protein expression in AML cells and induces sensitization to both the BH3 mimetic inhibitor of Bcl-xL, Bcl-2 and Bcl-w, ABT-737, and cytarabine. 26206337 8 43 theme Bcl-w 1581:1585 arg1 inhibitor 1550:1558 the BH3 mimetic inhibitor 1534:1558 the BH3 mimetic inhibitor of Bcl-xL, Bcl-2 and Bcl-w 1534:1585 Finally, we showed that 2-DG decreases Mcl-1 protein expression in AML cells and induces sensitization to both the BH3 mimetic inhibitor of Bcl-xL, Bcl-2 and Bcl-w, ABT-737, and cytarabine. 26206337 8 43 theme Bcl-w 1581:1585 arg1 cytarabine 1601:1610 cytarabine 1601:1610 cytarabine 1601:1610 Finally, we showed that 2-DG decreases Mcl-1 protein expression in AML cells and induces sensitization to both the BH3 mimetic inhibitor of Bcl-xL, Bcl-2 and Bcl-w, ABT-737, and cytarabine. 26206337 9 44 from window 1743:1748 arg1 subset 1755:1760 a subset 1753:1760 a subset of AML with mutated RTKs 1753:1785 In conclusion, 2-DG displays a significant antileukemic activity in AML with FLT3-ITD or KIT mutations, opening a new therapeutic window in a subset of AML with mutated RTKs. 26206337 6 45 theme antileukemic 1032:1043 arg1 marked 1079:1084 marked 1079:1084 marked 1079:1084 Moreover, the antileukemic activity of 2-DG was particularly marked in c-KIT-mutated cell lines and cell samples from core binding factor-AML patients. 26206337 6 45 theme antileukemic 1032:1043 arg1 activity 1045:1052 the antileukemic activity 1028:1052 the antileukemic activity of 2-DG 1028:1060 Moreover, the antileukemic activity of 2-DG was particularly marked in c-KIT-mutated cell lines and cell samples from core binding factor-AML patients. 26206337 2 46 theme human 344:348 arg1 lines 364:368 human leukemic cell lines 344:368 human leukemic cell lines cells 344:374 We used human leukemic cell lines cells, both in vitro and in vivo, as well as leukemic samples from AML patients to demonstrate the role of 2-DG in tumor cell growth inhibition. 26206337 1 47 theme tyrosine 263:270 arg1 kinases 272:278 receptor tyrosine kinases 254:278 receptor tyrosine kinases (RTK) commonly mutated in acute myeloid leukemia (AML) 254:333 We assessed the antileukemic activity of 2-deoxy-d-glucose (2-DG) through the modulation of expression of receptor tyrosine kinases (RTK) commonly mutated in acute myeloid leukemia (AML). 26206337 1 47 theme tyrosine 263:270 arg1 RTK 281:283 RTK 281:283 RTK 281:283 We assessed the antileukemic activity of 2-deoxy-d-glucose (2-DG) through the modulation of expression of receptor tyrosine kinases (RTK) commonly mutated in acute myeloid leukemia (AML). 26206337 7 48 theme Kasumi-1 1407:1414 arg1 cells 1416:1420 Kasumi-1 cells 1407:1420 Kasumi-1 cells 1407:1420 In these cells, 2-DG inhibited the cell-surface expression of c-KIT, abrogated STAT3 and MAPK-ERK pathways, and strongly downregulated the expression of the receptor resulting in a strong in vivo effect in NOD/SCID mice xenografted with Kasumi-1 cells. 26206337 3 49 theme c-KIT 653:657 arg1 expression 590:599 cell-surface expression 577:599 cell-surface expression 577:599 2-DG, through N-linked glycosylation inhibition, affected the cell-surface expression and cellular signaling of both FTL3-ITD and mutated c-KIT and induced apoptotic cell death. 26206337 3 49 theme c-KIT 653:657 arg1 signaling 614:622 cellular signaling 605:622 cellular signaling 605:622 2-DG, through N-linked glycosylation inhibition, affected the cell-surface expression and cellular signaling of both FTL3-ITD and mutated c-KIT and induced apoptotic cell death. 26206337 4 50 dep RTKs 732:735 arg1 RTKs 732:735 these mutated RTKs 718:735 these mutated RTKs (MV4-11, MOLM-14, Kasumi-1, and TF-1 c-KIT D816V) 718:785 Leukemic cells harboring these mutated RTKs (MV4-11, MOLM-14, Kasumi-1, and TF-1 c-KIT D816V) were the most sensitive to 2-DG treatment in vitro as compared with nonmutated cells. 26206337 4 50 dep RTKs 732:735 arg1 D816V 780:784 TF-1 c-KIT D816V 769:784 TF-1 c-KIT D816V 769:784 Leukemic cells harboring these mutated RTKs (MV4-11, MOLM-14, Kasumi-1, and TF-1 c-KIT D816V) were the most sensitive to 2-DG treatment in vitro as compared with nonmutated cells. 26206337 4 50 dep RTKs 732:735 arg1 Kasumi-1 755:762 Kasumi-1 755:762 Kasumi-1 755:762 Leukemic cells harboring these mutated RTKs (MV4-11, MOLM-14, Kasumi-1, and TF-1 c-KIT D816V) were the most sensitive to 2-DG treatment in vitro as compared with nonmutated cells. 26206337 4 50 dep RTKs 732:735 arg1 MOLM-14 746:752 MOLM-14 746:752 MOLM-14 746:752 Leukemic cells harboring these mutated RTKs (MV4-11, MOLM-14, Kasumi-1, and TF-1 c-KIT D816V) were the most sensitive to 2-DG treatment in vitro as compared with nonmutated cells. 26206337 4 50 dep RTKs 732:735 arg1 MV4-11 738:743 MV4-11 738:743 MV4-11 738:743 Leukemic cells harboring these mutated RTKs (MV4-11, MOLM-14, Kasumi-1, and TF-1 c-KIT D816V) were the most sensitive to 2-DG treatment in vitro as compared with nonmutated cells. 26206337 8 51 theme Bcl-xL 1563:1568 arg1 ABT-737 1588:1594 ABT-737 1588:1594 ABT-737 1588:1594 Finally, we showed that 2-DG decreases Mcl-1 protein expression in AML cells and induces sensitization to both the BH3 mimetic inhibitor of Bcl-xL, Bcl-2 and Bcl-w, ABT-737, and cytarabine. 26206337 8 51 theme Bcl-xL 1563:1568 arg1 inhibitor 1550:1558 the BH3 mimetic inhibitor 1534:1558 the BH3 mimetic inhibitor of Bcl-xL, Bcl-2 and Bcl-w 1534:1585 Finally, we showed that 2-DG decreases Mcl-1 protein expression in AML cells and induces sensitization to both the BH3 mimetic inhibitor of Bcl-xL, Bcl-2 and Bcl-w, ABT-737, and cytarabine. 26206337 8 51 theme Bcl-xL 1563:1568 arg1 cytarabine 1601:1610 cytarabine 1601:1610 cytarabine 1601:1610 Finally, we showed that 2-DG decreases Mcl-1 protein expression in AML cells and induces sensitization to both the BH3 mimetic inhibitor of Bcl-xL, Bcl-2 and Bcl-w, ABT-737, and cytarabine. 26206337 9 52 with AML 1765:1767 arg1 RTKs 1782:1785 mutated RTKs 1774:1785 mutated RTKs 1774:1785 In conclusion, 2-DG displays a significant antileukemic activity in AML with FLT3-ITD or KIT mutations, opening a new therapeutic window in a subset of AML with mutated RTKs. 26206337 7 53 theme NOD/SCID 1376:1383 arg1 mice 1385:1388 NOD/SCID mice 1376:1388 NOD/SCID mice xenografted with Kasumi-1 cells 1376:1420 In these cells, 2-DG inhibited the cell-surface expression of c-KIT, abrogated STAT3 and MAPK-ERK pathways, and strongly downregulated the expression of the receptor resulting in a strong in vivo effect in NOD/SCID mice xenografted with Kasumi-1 cells. 26206337 3 54 theme cell 681:684 arg1 death 686:690 apoptotic cell death 671:690 apoptotic cell death 671:690 2-DG, through N-linked glycosylation inhibition, affected the cell-surface expression and cellular signaling of both FTL3-ITD and mutated c-KIT and induced apoptotic cell death. 26206337 7 55 theme strong 1351:1356 arg1 effect 1366:1371 a strong in vivo effect 1349:1371 a strong in vivo effect in NOD/SCID mice xenografted with Kasumi-1 cells 1349:1420 In these cells, 2-DG inhibited the cell-surface expression of c-KIT, abrogated STAT3 and MAPK-ERK pathways, and strongly downregulated the expression of the receptor resulting in a strong in vivo effect in NOD/SCID mice xenografted with Kasumi-1 cells. 26206337 0 56 with Leukemia 105:112 arg1 Mutations 137:145 FLT3-ITD or c-KIT Mutations 119:145 FLT3-ITD or c-KIT Mutations 119:145 Antileukemic Activity of 2-Deoxy-d-Glucose through Inhibition of N-Linked Glycosylation in Acute Myeloid Leukemia with FLT3-ITD or c-KIT Mutations. 26206337 6 57 theme c-KIT-mutated 1089:1101 arg1 lines 1108:1112 c-KIT-mutated cell lines 1089:1112 c-KIT-mutated cell lines 1089:1112 Moreover, the antileukemic activity of 2-DG was particularly marked in c-KIT-mutated cell lines and cell samples from core binding factor-AML patients. 26206337 2 58 theme cell 491:494 arg1 growth 496:501 tumor cell growth 485:501 tumor cell growth inhibition 485:512 We used human leukemic cell lines cells, both in vitro and in vivo, as well as leukemic samples from AML patients to demonstrate the role of 2-DG in tumor cell growth inhibition. 26206337 2 59 from patients 441:448 arg1 lines 364:368 human leukemic cell lines 344:368 human leukemic cell lines cells 344:374 We used human leukemic cell lines cells, both in vitro and in vivo, as well as leukemic samples from AML patients to demonstrate the role of 2-DG in tumor cell growth inhibition. 26206337 2 59 from patients 441:448 arg1 samples 424:430 leukemic samples 415:430 leukemic samples from AML patients 415:448 We used human leukemic cell lines cells, both in vitro and in vivo, as well as leukemic samples from AML patients to demonstrate the role of 2-DG in tumor cell growth inhibition. 26206337 3 60 theme glycosylation 538:550 arg1 inhibition 552:561 N-linked glycosylation inhibition 529:561 N-linked glycosylation inhibition 529:561 2-DG, through N-linked glycosylation inhibition, affected the cell-surface expression and cellular signaling of both FTL3-ITD and mutated c-KIT and induced apoptotic cell death. 26206337 4 61 theme nonmutated 855:864 arg1 cells 866:870 nonmutated cells 855:870 nonmutated cells 855:870 Leukemic cells harboring these mutated RTKs (MV4-11, MOLM-14, Kasumi-1, and TF-1 c-KIT D816V) were the most sensitive to 2-DG treatment in vitro as compared with nonmutated cells. 26206337 7 62 theme receptor 1327:1334 arg1 expression 1309:1318 the expression 1305:1318 the expression of the receptor resulting in a strong in vivo effect in NOD/SCID mice xenografted with Kasumi-1 cells 1305:1420 In these cells, 2-DG inhibited the cell-surface expression of c-KIT, abrogated STAT3 and MAPK-ERK pathways, and strongly downregulated the expression of the receptor resulting in a strong in vivo effect in NOD/SCID mice xenografted with Kasumi-1 cells. 26206337 7 63 dep in 1358:1359 arg1 vivo 1361:1364 vivo 1361:1364 vivo 1361:1364 In these cells, 2-DG inhibited the cell-surface expression of c-KIT, abrogated STAT3 and MAPK-ERK pathways, and strongly downregulated the expression of the receptor resulting in a strong in vivo effect in NOD/SCID mice xenografted with Kasumi-1 cells. 26206337 2 64 from role 469:472 arg1 inhibition 503:512 tumor cell growth inhibition 485:512 tumor cell growth inhibition 485:512 We used human leukemic cell lines cells, both in vitro and in vivo, as well as leukemic samples from AML patients to demonstrate the role of 2-DG in tumor cell growth inhibition. 26206337 5 65 theme inhibitor 989:997 arg1 quizartinib 1005:1015 the tyrosine kinase inhibitor (TKI) quizartinib 969:1015 the tyrosine kinase inhibitor (TKI) quizartinib 969:1015 2-DG activity was also demonstrated in leukemic cells harboring FLT3-TKD mutations resistant to the tyrosine kinase inhibitor (TKI) quizartinib. 26206337 9 66 theme significant 1644:1654 arg1 activity 1669:1676 a significant antileukemic activity 1642:1676 a significant antileukemic activity in AML 1642:1683 In conclusion, 2-DG displays a significant antileukemic activity in AML with FLT3-ITD or KIT mutations, opening a new therapeutic window in a subset of AML with mutated RTKs. 26206337 6 67 theme binding 1141:1147 arg1 patients 1160:1167 core binding factor-AML patients 1136:1167 core binding factor-AML patients 1136:1167 Moreover, the antileukemic activity of 2-DG was particularly marked in c-KIT-mutated cell lines and cell samples from core binding factor-AML patients. 26206337 5 68 theme TKI 1000:1002 arg1 quizartinib 1005:1015 the tyrosine kinase inhibitor (TKI) quizartinib 969:1015 the tyrosine kinase inhibitor (TKI) quizartinib 969:1015 2-DG activity was also demonstrated in leukemic cells harboring FLT3-TKD mutations resistant to the tyrosine kinase inhibitor (TKI) quizartinib. 26206337 0 69 theme Myeloid 97:103 arg1 Leukemia 105:112 Acute Myeloid Leukemia 91:112 Acute Myeloid Leukemia with FLT3-ITD or c-KIT Mutations 91:145 Antileukemic Activity of 2-Deoxy-d-Glucose through Inhibition of N-Linked Glycosylation in Acute Myeloid Leukemia with FLT3-ITD or c-KIT Mutations. 26206337 1 70 theme antileukemic 164:175 arg1 activity 177:184 the antileukemic activity 160:184 the antileukemic activity of 2-deoxy-d-glucose (2-DG) 160:212 We assessed the antileukemic activity of 2-deoxy-d-glucose (2-DG) through the modulation of expression of receptor tyrosine kinases (RTK) commonly mutated in acute myeloid leukemia (AML). 26206337 2 71 theme AML 437:439 arg1 patients 441:448 AML patients 437:448 AML patients 437:448 We used human leukemic cell lines cells, both in vitro and in vivo, as well as leukemic samples from AML patients to demonstrate the role of 2-DG in tumor cell growth inhibition. 26206337 2 72 used used 339:342 arg2 We 336:337 We 336:337 We 336:337 We used human leukemic cell lines cells, both in vitro and in vivo, as well as leukemic samples from AML patients to demonstrate the role of 2-DG in tumor cell growth inhibition. 26206337 4 73 theme mutated 724:730 arg1 RTKs 732:735 these mutated RTKs 718:735 these mutated RTKs (MV4-11, MOLM-14, Kasumi-1, and TF-1 c-KIT D816V) 718:785 Leukemic cells harboring these mutated RTKs (MV4-11, MOLM-14, Kasumi-1, and TF-1 c-KIT D816V) were the most sensitive to 2-DG treatment in vitro as compared with nonmutated cells. 26206337 4 73 theme mutated 724:730 arg1 D816V 780:784 TF-1 c-KIT D816V 769:784 TF-1 c-KIT D816V 769:784 Leukemic cells harboring these mutated RTKs (MV4-11, MOLM-14, Kasumi-1, and TF-1 c-KIT D816V) were the most sensitive to 2-DG treatment in vitro as compared with nonmutated cells. 26206337 4 73 theme mutated 724:730 arg1 Kasumi-1 755:762 Kasumi-1 755:762 Kasumi-1 755:762 Leukemic cells harboring these mutated RTKs (MV4-11, MOLM-14, Kasumi-1, and TF-1 c-KIT D816V) were the most sensitive to 2-DG treatment in vitro as compared with nonmutated cells. 26206337 4 73 theme mutated 724:730 arg1 MOLM-14 746:752 MOLM-14 746:752 MOLM-14 746:752 Leukemic cells harboring these mutated RTKs (MV4-11, MOLM-14, Kasumi-1, and TF-1 c-KIT D816V) were the most sensitive to 2-DG treatment in vitro as compared with nonmutated cells. 26206337 4 73 theme mutated 724:730 arg1 MV4-11 738:743 MV4-11 738:743 MV4-11 738:743 Leukemic cells harboring these mutated RTKs (MV4-11, MOLM-14, Kasumi-1, and TF-1 c-KIT D816V) were the most sensitive to 2-DG treatment in vitro as compared with nonmutated cells. 26206337 9 74 theme KIT 1702:1704 arg1 mutations 1706:1714 KIT mutations 1702:1714 KIT mutations 1702:1714 In conclusion, 2-DG displays a significant antileukemic activity in AML with FLT3-ITD or KIT mutations, opening a new therapeutic window in a subset of AML with mutated RTKs. 26206337 0 75 from Inhibition 51:60 arg1 Leukemia 105:112 Acute Myeloid Leukemia 91:112 Acute Myeloid Leukemia with FLT3-ITD or c-KIT Mutations 91:145 Antileukemic Activity of 2-Deoxy-d-Glucose through Inhibition of N-Linked Glycosylation in Acute Myeloid Leukemia with FLT3-ITD or c-KIT Mutations. 26206337 6 76 from samples 1123:1129 arg1 marked 1079:1084 marked 1079:1084 marked 1079:1084 Moreover, the antileukemic activity of 2-DG was particularly marked in c-KIT-mutated cell lines and cell samples from core binding factor-AML patients. 26206337 6 76 from samples 1123:1129 arg1 activity 1045:1052 the antileukemic activity 1028:1052 the antileukemic activity of 2-DG 1028:1060 Moreover, the antileukemic activity of 2-DG was particularly marked in c-KIT-mutated cell lines and cell samples from core binding factor-AML patients. 26206337 4 77 theme Leukemic 693:700 arg1 sensitive 801:809 sensitive 801:809 sensitive 801:809 Leukemic cells harboring these mutated RTKs (MV4-11, MOLM-14, Kasumi-1, and TF-1 c-KIT D816V) were the most sensitive to 2-DG treatment in vitro as compared with nonmutated cells. 26206337 4 77 theme Leukemic 693:700 arg1 cells 702:706 Leukemic cells 693:706 Leukemic cells harboring these mutated RTKs (MV4-11, MOLM-14, Kasumi-1, and TF-1 c-KIT D816V) 693:785 Leukemic cells harboring these mutated RTKs (MV4-11, MOLM-14, Kasumi-1, and TF-1 c-KIT D816V) were the most sensitive to 2-DG treatment in vitro as compared with nonmutated cells. 26206337 0 78 theme 2-Deoxy-d-Glucose 25:41 arg1 Activity 13:20 Antileukemic Activity 0:20 Antileukemic Activity of 2-Deoxy-d-Glucose through Inhibition of N-Linked Glycosylation in Acute Myeloid Leukemia with FLT3-ITD or c-KIT Mutations. 0:146 Antileukemic Activity of 2-Deoxy-d-Glucose through Inhibition of N-Linked Glycosylation in Acute Myeloid Leukemia with FLT3-ITD or c-KIT Mutations. 26206337 3 79 theme cellular 605:612 arg1 signaling 614:622 cellular signaling 605:622 cellular signaling 605:622 2-DG, through N-linked glycosylation inhibition, affected the cell-surface expression and cellular signaling of both FTL3-ITD and mutated c-KIT and induced apoptotic cell death. 26206337 5 80 theme resistant 956:964 arg1 mutations 946:954 FLT3-TKD mutations 937:954 FLT3-TKD mutations resistant to the tyrosine kinase inhibitor (TKI) quizartinib 937:1015 2-DG activity was also demonstrated in leukemic cells harboring FLT3-TKD mutations resistant to the tyrosine kinase inhibitor (TKI) quizartinib. 26206337 7 81 theme c-KIT 1232:1236 arg1 expression 1218:1227 the cell-surface expression 1201:1227 the cell-surface expression of c-KIT 1201:1236 In these cells, 2-DG inhibited the cell-surface expression of c-KIT, abrogated STAT3 and MAPK-ERK pathways, and strongly downregulated the expression of the receptor resulting in a strong in vivo effect in NOD/SCID mice xenografted with Kasumi-1 cells. 26206337 3 82 link N-linked 529:536 arg1 glycosylation 538:550 N-linked glycosylation 529:550 N-linked glycosylation inhibition 529:561 2-DG, through N-linked glycosylation inhibition, affected the cell-surface expression and cellular signaling of both FTL3-ITD and mutated c-KIT and induced apoptotic cell death. 26206337 9 83 dep displays 1633:1640 arg1 opening 1717:1723 opening 1717:1723 opening 1717:1723 In conclusion, 2-DG displays a significant antileukemic activity in AML with FLT3-ITD or KIT mutations, opening a new therapeutic window in a subset of AML with mutated RTKs. 26206337 0 84 theme N-Linked 65:72 arg1 Glycosylation 74:86 N-Linked Glycosylation 65:86 N-Linked Glycosylation 65:86 Antileukemic Activity of 2-Deoxy-d-Glucose through Inhibition of N-Linked Glycosylation in Acute Myeloid Leukemia with FLT3-ITD or c-KIT Mutations. 26206337 1 85 theme myeloid 312:318 arg1 AML 330:332 AML 330:332 AML 330:332 We assessed the antileukemic activity of 2-deoxy-d-glucose (2-DG) through the modulation of expression of receptor tyrosine kinases (RTK) commonly mutated in acute myeloid leukemia (AML). 26206337 1 85 theme myeloid 312:318 arg1 leukemia 320:327 acute myeloid leukemia 306:327 acute myeloid leukemia (AML) 306:333 We assessed the antileukemic activity of 2-deoxy-d-glucose (2-DG) through the modulation of expression of receptor tyrosine kinases (RTK) commonly mutated in acute myeloid leukemia (AML). 26206337 8 86 theme protein 1468:1474 arg1 expression 1476:1485 Mcl-1 protein expression 1462:1485 Mcl-1 protein expression in AML cells 1462:1498 Finally, we showed that 2-DG decreases Mcl-1 protein expression in AML cells and induces sensitization to both the BH3 mimetic inhibitor of Bcl-xL, Bcl-2 and Bcl-w, ABT-737, and cytarabine. 26206337 3 87 theme FTL3-ITD 632:639 arg1 expression 590:599 cell-surface expression 577:599 cell-surface expression 577:599 2-DG, through N-linked glycosylation inhibition, affected the cell-surface expression and cellular signaling of both FTL3-ITD and mutated c-KIT and induced apoptotic cell death. 26206337 3 87 theme FTL3-ITD 632:639 arg1 signaling 614:622 cellular signaling 605:622 cellular signaling 605:622 2-DG, through N-linked glycosylation inhibition, affected the cell-surface expression and cellular signaling of both FTL3-ITD and mutated c-KIT and induced apoptotic cell death. 26206337 4 88 theme TF-1 769:772 arg1 RTKs 732:735 these mutated RTKs 718:735 these mutated RTKs (MV4-11, MOLM-14, Kasumi-1, and TF-1 c-KIT D816V) 718:785 Leukemic cells harboring these mutated RTKs (MV4-11, MOLM-14, Kasumi-1, and TF-1 c-KIT D816V) were the most sensitive to 2-DG treatment in vitro as compared with nonmutated cells. 26206337 4 88 theme TF-1 769:772 arg1 D816V 780:784 TF-1 c-KIT D816V 769:784 TF-1 c-KIT D816V 769:784 Leukemic cells harboring these mutated RTKs (MV4-11, MOLM-14, Kasumi-1, and TF-1 c-KIT D816V) were the most sensitive to 2-DG treatment in vitro as compared with nonmutated cells. 26206337 6 89 theme 2-DG 1057:1060 arg1 marked 1079:1084 marked 1079:1084 marked 1079:1084 Moreover, the antileukemic activity of 2-DG was particularly marked in c-KIT-mutated cell lines and cell samples from core binding factor-AML patients. 26206337 6 89 theme 2-DG 1057:1060 arg1 activity 1045:1052 the antileukemic activity 1028:1052 the antileukemic activity of 2-DG 1028:1060 Moreover, the antileukemic activity of 2-DG was particularly marked in c-KIT-mutated cell lines and cell samples from core binding factor-AML patients. 26206337 2 90 dep lines 364:368 arg1 cells 370:374 cells 370:374 human leukemic cell lines cells 344:374 We used human leukemic cell lines cells, both in vitro and in vivo, as well as leukemic samples from AML patients to demonstrate the role of 2-DG in tumor cell growth inhibition. 26206337 1 91 theme expression 240:249 arg1 modulation 226:235 the modulation 222:235 the modulation of expression of receptor tyrosine kinases (RTK) commonly mutated in acute myeloid leukemia (AML) 222:333 We assessed the antileukemic activity of 2-deoxy-d-glucose (2-DG) through the modulation of expression of receptor tyrosine kinases (RTK) commonly mutated in acute myeloid leukemia (AML). 26206337 9 92 from activity 1669:1676 arg1 AML 1681:1683 AML 1681:1683 AML 1681:1683 In conclusion, 2-DG displays a significant antileukemic activity in AML with FLT3-ITD or KIT mutations, opening a new therapeutic window in a subset of AML with mutated RTKs. 26206337 5 93 theme FLT3-TKD 937:944 arg1 mutations 946:954 FLT3-TKD mutations 937:954 FLT3-TKD mutations resistant to the tyrosine kinase inhibitor (TKI) quizartinib 937:1015 2-DG activity was also demonstrated in leukemic cells harboring FLT3-TKD mutations resistant to the tyrosine kinase inhibitor (TKI) quizartinib. 26206337 9 94 theme AML 1765:1767 arg1 subset 1755:1760 a subset 1753:1760 a subset of AML with mutated RTKs 1753:1785 In conclusion, 2-DG displays a significant antileukemic activity in AML with FLT3-ITD or KIT mutations, opening a new therapeutic window in a subset of AML with mutated RTKs. 26206337 8 95 theme mimetic 1542:1548 arg1 ABT-737 1588:1594 ABT-737 1588:1594 ABT-737 1588:1594 Finally, we showed that 2-DG decreases Mcl-1 protein expression in AML cells and induces sensitization to both the BH3 mimetic inhibitor of Bcl-xL, Bcl-2 and Bcl-w, ABT-737, and cytarabine. 26206337 8 95 theme mimetic 1542:1548 arg1 inhibitor 1550:1558 the BH3 mimetic inhibitor 1534:1558 the BH3 mimetic inhibitor of Bcl-xL, Bcl-2 and Bcl-w 1534:1585 Finally, we showed that 2-DG decreases Mcl-1 protein expression in AML cells and induces sensitization to both the BH3 mimetic inhibitor of Bcl-xL, Bcl-2 and Bcl-w, ABT-737, and cytarabine. 26206337 2 96 theme leukemic 350:357 arg1 lines 364:368 human leukemic cell lines 344:368 human leukemic cell lines cells 344:374 We used human leukemic cell lines cells, both in vitro and in vivo, as well as leukemic samples from AML patients to demonstrate the role of 2-DG in tumor cell growth inhibition. 26206337 1 97 theme receptor 254:261 arg1 kinases 272:278 receptor tyrosine kinases 254:278 receptor tyrosine kinases (RTK) commonly mutated in acute myeloid leukemia (AML) 254:333 We assessed the antileukemic activity of 2-deoxy-d-glucose (2-DG) through the modulation of expression of receptor tyrosine kinases (RTK) commonly mutated in acute myeloid leukemia (AML). 26206337 1 97 theme receptor 254:261 arg1 RTK 281:283 RTK 281:283 RTK 281:283 We assessed the antileukemic activity of 2-deoxy-d-glucose (2-DG) through the modulation of expression of receptor tyrosine kinases (RTK) commonly mutated in acute myeloid leukemia (AML). 25979332 0 0 theme CORE 95:98 arg1 FUCOSYLATION 100:111 CORE FUCOSYLATION 95:111 CORE FUCOSYLATION 95:111 Loss of α1,6-Fucosyltransferase Decreases Hippocampal Long Term Potentiation: IMPLICATIONS FOR CORE FUCOSYLATION IN THE REGULATION OF AMPA RECEPTOR HETEROMERIZATION AND CELLULAR SIGNALING. 25979332 6 1 theme protein 982:988 arg1 mediator 1023:1030 an important mediator 1010:1030 an important mediator of learning and memory in postsynapses 1010:1069 Unexpectedly, the phosphorylation levels of calcium/calmodulin-dependent protein kinase II (CaMKII), an important mediator of learning and memory in postsynapses, were greatly increased in Fut8(-/-) mice. 25979332 6 1 theme protein 982:988 arg1 kinase 990:995 calcium/calmodulin-dependent protein kinase II 953:998 calcium/calmodulin-dependent protein kinase II (CaMKII) 953:1007 Unexpectedly, the phosphorylation levels of calcium/calmodulin-dependent protein kinase II (CaMKII), an important mediator of learning and memory in postsynapses, were greatly increased in Fut8(-/-) mice. 25979332 6 1 theme protein 982:988 arg1 CaMKII 1001:1006 CaMKII 1001:1006 CaMKII 1001:1006 Unexpectedly, the phosphorylation levels of calcium/calmodulin-dependent protein kinase II (CaMKII), an important mediator of learning and memory in postsynapses, were greatly increased in Fut8(-/-) mice. 25979332 9 2 theme postsynaptic 1650:1661 arg1 depolarization 1663:1676 postsynaptic depolarization 1650:1676 postsynaptic depolarization 1650:1676 Taken together, loss of core fucosylation on AMPARs enhanced their heteromerization, which increase sensitivity for postsynaptic depolarization and persistently activate N-methyl-d-aspartate receptors as well as Ca(2+) influx and CaMKII and then impair LTP. 25979332 5 3 from decline 857:863 arg1 E-LTP 868:872 E-LTP 868:872 E-LTP 868:872 Tetraethylammonium-induced LTP showed no significant differences, suggesting that the decline in E-LTP was caused by postsynaptic events. 25979332 4 4 theme E-LTP 680:684 arg1 scale 671:675 The scale 667:675 The scale of E-LTP induced by high frequency stimulation 667:722 The scale of E-LTP induced by high frequency stimulation was significantly decreased in Fut8(-/-) mice. 25979332 9 5 theme 2+ 1749:1750 arg1 influx 1753:1758 Ca(2+) influx 1746:1758 Ca(2+) influx 1746:1758 Taken together, loss of core fucosylation on AMPARs enhanced their heteromerization, which increase sensitivity for postsynaptic depolarization and persistently activate N-methyl-d-aspartate receptors as well as Ca(2+) influx and CaMKII and then impair LTP. 25979332 8 6 theme calcium 1486:1492 arg1 imaging 1494:1500 Fura-2 calcium imaging 1479:1500 Fura-2 calcium imaging using primary cultured neurons 1479:1531 The activation of AMPARs was further confirmed by Fura-2 calcium imaging using primary cultured neurons. 25979332 7 7 from levels 1129:1134 arg1 density 1227:1233 the postsynaptic density 1210:1233 the postsynaptic density 1210:1233 The expression levels of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors (AMPARs) in the postsynaptic density were enhanced in Fut8(-/-) mice, although there were no significant differences in the total expression levels, implicating that AMPARs without core fucosylation might exist in an active state. 25979332 3 8 theme underlying 512:521 arg1 mechanism 533:541 the underlying molecular mechanism 508:541 the underlying molecular mechanism 508:541 To understand the underlying molecular mechanism, we analyzed early form long term potentiation (E-LTP), which is closely related to learning and memory in the hippocampus. 25979332 1 9 theme fucose 273:278 arg1 residue 280:286 a fucose residue 271:286 a fucose residue 271:286 Core fucosylation is catalyzed by α1,6-fucosyltransferase (FUT8), which transfers a fucose residue to the innermost GlcNAc residue via α1,6-linkage on N-glycans in mammals. 25979332 2 10 from phenotype 450:458 arg1 memory 486:491 working memory 478:491 working memory 478:491 We previously reported that Fut8-knock-out (Fut8(-/-)) mice showed a schizophrenia-like phenotype and a decrease in working memory. 25979332 4 11 theme Fut8 755:758 arg1 mice 765:768 Fut8(-/-) mice 755:768 Fut8(-/-) mice 755:768 The scale of E-LTP induced by high frequency stimulation was significantly decreased in Fut8(-/-) mice. 25979332 3 12 from learning 627:634 arg1 hippocampus 654:664 the hippocampus 650:664 the hippocampus 650:664 To understand the underlying molecular mechanism, we analyzed early form long term potentiation (E-LTP), which is closely related to learning and memory in the hippocampus. 25979332 2 13 from decrease 466:473 arg1 memory 486:491 working memory 478:491 working memory 478:491 We previously reported that Fut8-knock-out (Fut8(-/-)) mice showed a schizophrenia-like phenotype and a decrease in working memory. 25979332 1 14 from α1,6-linkage 324:335 arg1 mammals 353:359 mammals 353:359 mammals 353:359 Core fucosylation is catalyzed by α1,6-fucosyltransferase (FUT8), which transfers a fucose residue to the innermost GlcNAc residue via α1,6-linkage on N-glycans in mammals. 25979332 1 14 from α1,6-linkage 324:335 arg1 N-glycans 340:348 N-glycans 340:348 N-glycans 340:348 Core fucosylation is catalyzed by α1,6-fucosyltransferase (FUT8), which transfers a fucose residue to the innermost GlcNAc residue via α1,6-linkage on N-glycans in mammals. 25979332 3 15 theme early 556:560 arg1 E-LTP 591:595 E-LTP 591:595 E-LTP 591:595 To understand the underlying molecular mechanism, we analyzed early form long term potentiation (E-LTP), which is closely related to learning and memory in the hippocampus. 25979332 3 15 theme early 556:560 arg1 potentiation 577:588 early form long term potentiation 556:588 early form long term potentiation (E-LTP) 556:596 To understand the underlying molecular mechanism, we analyzed early form long term potentiation (E-LTP), which is closely related to learning and memory in the hippocampus. 25979332 6 16 theme -/- 1103:1105 arg1 mice 1108:1111 Fut8(-/-) mice 1098:1111 Fut8(-/-) mice 1098:1111 Unexpectedly, the phosphorylation levels of calcium/calmodulin-dependent protein kinase II (CaMKII), an important mediator of learning and memory in postsynapses, were greatly increased in Fut8(-/-) mice. 25979332 5 17 theme Tetraethylammonium-induced 771:796 arg1 LTP 798:800 Tetraethylammonium-induced LTP 771:800 Tetraethylammonium-induced LTP 771:800 Tetraethylammonium-induced LTP showed no significant differences, suggesting that the decline in E-LTP was caused by postsynaptic events. 25979332 8 18 theme cultured 1516:1523 arg1 neurons 1525:1531 primary cultured neurons 1508:1531 primary cultured neurons 1508:1531 The activation of AMPARs was further confirmed by Fura-2 calcium imaging using primary cultured neurons. 25979332 7 19 theme receptors 1188:1196 arg1 levels 1129:1134 The expression levels 1114:1134 The expression levels of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors (AMPARs) in the postsynaptic density 1114:1233 The expression levels of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors (AMPARs) in the postsynaptic density were enhanced in Fut8(-/-) mice, although there were no significant differences in the total expression levels, implicating that AMPARs without core fucosylation might exist in an active state. 25979332 6 20 theme memory 1048:1053 arg1 kinase 990:995 calcium/calmodulin-dependent protein kinase II 953:998 calcium/calmodulin-dependent protein kinase II (CaMKII) 953:1007 Unexpectedly, the phosphorylation levels of calcium/calmodulin-dependent protein kinase II (CaMKII), an important mediator of learning and memory in postsynapses, were greatly increased in Fut8(-/-) mice. 25979332 6 20 theme memory 1048:1053 arg1 mediator 1023:1030 an important mediator 1010:1030 an important mediator of learning and memory in postsynapses 1010:1069 Unexpectedly, the phosphorylation levels of calcium/calmodulin-dependent protein kinase II (CaMKII), an important mediator of learning and memory in postsynapses, were greatly increased in Fut8(-/-) mice. 25979332 2 21 dep Fut8-knock-out 390:403 arg1 -/- 411:413 -/- 411:413 -/- 411:413 We previously reported that Fut8-knock-out (Fut8(-/-)) mice showed a schizophrenia-like phenotype and a decrease in working memory. 25979332 2 21 dep Fut8-knock-out 390:403 arg1 Fut8 406:409 Fut8 406:409 Fut8(-/-) 406:414 We previously reported that Fut8-knock-out (Fut8(-/-)) mice showed a schizophrenia-like phenotype and a decrease in working memory. 25979332 1 22 theme Core 189:192 arg1 fucosylation 194:205 Core fucosylation 189:205 Core fucosylation 189:205 Core fucosylation is catalyzed by α1,6-fucosyltransferase (FUT8), which transfers a fucose residue to the innermost GlcNAc residue via α1,6-linkage on N-glycans in mammals. 25979332 3 23 from memory 640:645 arg1 hippocampus 654:664 the hippocampus 650:664 the hippocampus 650:664 To understand the underlying molecular mechanism, we analyzed early form long term potentiation (E-LTP), which is closely related to learning and memory in the hippocampus. 25979332 5 24 theme postsynaptic 888:899 arg1 events 901:906 postsynaptic events 888:906 postsynaptic events 888:906 Tetraethylammonium-induced LTP showed no significant differences, suggesting that the decline in E-LTP was caused by postsynaptic events. 25979332 2 25 theme working 478:484 arg1 memory 486:491 working memory 478:491 working memory 478:491 We previously reported that Fut8-knock-out (Fut8(-/-)) mice showed a schizophrenia-like phenotype and a decrease in working memory. 25979332 7 26 theme expression 1328:1337 arg1 levels 1339:1344 the total expression levels 1318:1344 the total expression levels 1318:1344 The expression levels of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors (AMPARs) in the postsynaptic density were enhanced in Fut8(-/-) mice, although there were no significant differences in the total expression levels, implicating that AMPARs without core fucosylation might exist in an active state. 25979332 3 27 theme term 572:575 arg1 E-LTP 591:595 E-LTP 591:595 E-LTP 591:595 To understand the underlying molecular mechanism, we analyzed early form long term potentiation (E-LTP), which is closely related to learning and memory in the hippocampus. 25979332 3 27 theme term 572:575 arg1 potentiation 577:588 early form long term potentiation 556:588 early form long term potentiation (E-LTP) 556:596 To understand the underlying molecular mechanism, we analyzed early form long term potentiation (E-LTP), which is closely related to learning and memory in the hippocampus. 25979332 8 28 theme primary 1508:1514 arg1 neurons 1525:1531 primary cultured neurons 1508:1531 primary cultured neurons 1508:1531 The activation of AMPARs was further confirmed by Fura-2 calcium imaging using primary cultured neurons. 25979332 9 29 theme core 1558:1561 arg1 fucosylation 1563:1574 core fucosylation 1558:1574 core fucosylation on AMPARs 1558:1584 Taken together, loss of core fucosylation on AMPARs enhanced their heteromerization, which increase sensitivity for postsynaptic depolarization and persistently activate N-methyl-d-aspartate receptors as well as Ca(2+) influx and CaMKII and then impair LTP. 25979332 9 30 theme fucosylation 1563:1574 arg1 loss 1550:1553 loss 1550:1553 loss of core fucosylation on AMPARs 1550:1584 Taken together, loss of core fucosylation on AMPARs enhanced their heteromerization, which increase sensitivity for postsynaptic depolarization and persistently activate N-methyl-d-aspartate receptors as well as Ca(2+) influx and CaMKII and then impair LTP. 25979332 2 31 theme schizophrenia-like 431:448 arg1 phenotype 450:458 a schizophrenia-like phenotype 429:458 a schizophrenia-like phenotype 429:458 We previously reported that Fut8-knock-out (Fut8(-/-)) mice showed a schizophrenia-like phenotype and a decrease in working memory. 25979332 1 32 theme innermost 295:303 arg1 residue 312:318 the innermost GlcNAc residue 291:318 the innermost GlcNAc residue via α1,6-linkage on N-glycans in mammals 291:359 Core fucosylation is catalyzed by α1,6-fucosyltransferase (FUT8), which transfers a fucose residue to the innermost GlcNAc residue via α1,6-linkage on N-glycans in mammals. 25979332 0 33 theme AMPA 134:137 arg1 RECEPTOR 139:146 AMPA RECEPTOR HETEROMERIZATION AND CELLULAR SIGNALING 134:186 RECEPTOR 139:146 Loss of α1,6-Fucosyltransferase Decreases Hippocampal Long Term Potentiation: IMPLICATIONS FOR CORE FUCOSYLATION IN THE REGULATION OF AMPA RECEPTOR HETEROMERIZATION AND CELLULAR SIGNALING. 25979332 3 34 theme form 562:565 arg1 E-LTP 591:595 E-LTP 591:595 E-LTP 591:595 To understand the underlying molecular mechanism, we analyzed early form long term potentiation (E-LTP), which is closely related to learning and memory in the hippocampus. 25979332 3 34 theme form 562:565 arg1 potentiation 577:588 early form long term potentiation 556:588 early form long term potentiation (E-LTP) 556:596 To understand the underlying molecular mechanism, we analyzed early form long term potentiation (E-LTP), which is closely related to learning and memory in the hippocampus. 25979332 7 35 theme core 1379:1382 arg1 fucosylation 1384:1395 core fucosylation 1379:1395 core fucosylation 1379:1395 The expression levels of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors (AMPARs) in the postsynaptic density were enhanced in Fut8(-/-) mice, although there were no significant differences in the total expression levels, implicating that AMPARs without core fucosylation might exist in an active state. 25979332 7 36 theme significant 1291:1301 arg1 differences 1303:1313 no significant differences 1288:1313 no significant differences 1288:1313 The expression levels of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors (AMPARs) in the postsynaptic density were enhanced in Fut8(-/-) mice, although there were no significant differences in the total expression levels, implicating that AMPARs without core fucosylation might exist in an active state. 25979332 0 37 theme α1,6-Fucosyltransferase 8:30 arg1 Loss 0:3 Loss 0:3 Loss of α1,6-Fucosyltransferase 0:30 Loss of α1,6-Fucosyltransferase Decreases Hippocampal Long Term Potentiation: IMPLICATIONS FOR CORE FUCOSYLATION IN THE REGULATION OF AMPA RECEPTOR HETEROMERIZATION AND CELLULAR SIGNALING. 25979332 1 38 theme GlcNAc 305:310 arg1 residue 312:318 the innermost GlcNAc residue 291:318 the innermost GlcNAc residue via α1,6-linkage on N-glycans in mammals 291:359 Core fucosylation is catalyzed by α1,6-fucosyltransferase (FUT8), which transfers a fucose residue to the innermost GlcNAc residue via α1,6-linkage on N-glycans in mammals. 25979332 4 39 theme -/- 760:762 arg1 mice 765:768 Fut8(-/-) mice 755:768 Fut8(-/-) mice 755:768 The scale of E-LTP induced by high frequency stimulation was significantly decreased in Fut8(-/-) mice. 25979332 3 40 theme long 567:570 arg1 E-LTP 591:595 E-LTP 591:595 E-LTP 591:595 To understand the underlying molecular mechanism, we analyzed early form long term potentiation (E-LTP), which is closely related to learning and memory in the hippocampus. 25979332 3 40 theme long 567:570 arg1 potentiation 577:588 early form long term potentiation 556:588 early form long term potentiation (E-LTP) 556:596 To understand the underlying molecular mechanism, we analyzed early form long term potentiation (E-LTP), which is closely related to learning and memory in the hippocampus. 25979332 3 41 theme molecular 523:531 arg1 mechanism 533:541 the underlying molecular mechanism 508:541 the underlying molecular mechanism 508:541 To understand the underlying molecular mechanism, we analyzed early form long term potentiation (E-LTP), which is closely related to learning and memory in the hippocampus. 25979332 0 42 theme Long 54:57 arg1 Potentiation 64:75 Hippocampal Long Term Potentiation 42:75 Hippocampal Long Term Potentiation: IMPLICATIONS FOR CORE FUCOSYLATION 42:111 Loss of α1,6-Fucosyltransferase Decreases Hippocampal Long Term Potentiation: IMPLICATIONS FOR CORE FUCOSYLATION IN THE REGULATION OF AMPA RECEPTOR HETEROMERIZATION AND CELLULAR SIGNALING. 25979332 6 43 theme calcium/calmodulin-dependent 953:980 arg1 mediator 1023:1030 an important mediator 1010:1030 an important mediator of learning and memory in postsynapses 1010:1069 Unexpectedly, the phosphorylation levels of calcium/calmodulin-dependent protein kinase II (CaMKII), an important mediator of learning and memory in postsynapses, were greatly increased in Fut8(-/-) mice. 25979332 6 43 theme calcium/calmodulin-dependent 953:980 arg1 kinase 990:995 calcium/calmodulin-dependent protein kinase II 953:998 calcium/calmodulin-dependent protein kinase II (CaMKII) 953:1007 Unexpectedly, the phosphorylation levels of calcium/calmodulin-dependent protein kinase II (CaMKII), an important mediator of learning and memory in postsynapses, were greatly increased in Fut8(-/-) mice. 25979332 6 43 theme calcium/calmodulin-dependent 953:980 arg1 CaMKII 1001:1006 CaMKII 1001:1006 CaMKII 1001:1006 Unexpectedly, the phosphorylation levels of calcium/calmodulin-dependent protein kinase II (CaMKII), an important mediator of learning and memory in postsynapses, were greatly increased in Fut8(-/-) mice. 25979332 9 44 theme Ca 1746:1747 arg1 influx 1753:1758 Ca(2+) influx 1746:1758 Ca(2+) influx 1746:1758 Taken together, loss of core fucosylation on AMPARs enhanced their heteromerization, which increase sensitivity for postsynaptic depolarization and persistently activate N-methyl-d-aspartate receptors as well as Ca(2+) influx and CaMKII and then impair LTP. 25979332 7 45 theme -/- 1257:1259 arg1 mice 1262:1265 Fut8(-/-) mice 1252:1265 Fut8(-/-) mice 1252:1265 The expression levels of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors (AMPARs) in the postsynaptic density were enhanced in Fut8(-/-) mice, although there were no significant differences in the total expression levels, implicating that AMPARs without core fucosylation might exist in an active state. 25979332 0 46 dep Potentiation 64:75 arg1 IMPLICATIONS 78:89 IMPLICATIONS 78:89 Hippocampal Long Term Potentiation: IMPLICATIONS FOR CORE FUCOSYLATION 42:111 Loss of α1,6-Fucosyltransferase Decreases Hippocampal Long Term Potentiation: IMPLICATIONS FOR CORE FUCOSYLATION IN THE REGULATION OF AMPA RECEPTOR HETEROMERIZATION AND CELLULAR SIGNALING. 25979332 0 47 theme Hippocampal 42:52 arg1 Potentiation 64:75 Hippocampal Long Term Potentiation 42:75 Hippocampal Long Term Potentiation: IMPLICATIONS FOR CORE FUCOSYLATION 42:111 Loss of α1,6-Fucosyltransferase Decreases Hippocampal Long Term Potentiation: IMPLICATIONS FOR CORE FUCOSYLATION IN THE REGULATION OF AMPA RECEPTOR HETEROMERIZATION AND CELLULAR SIGNALING. 25979332 9 48 gly fucosylation 1563:1574 arg1 AMPARs 1579:1584 AMPARs 1579:1584 AMPARs 1579:1584 Taken together, loss of core fucosylation on AMPARs enhanced their heteromerization, which increase sensitivity for postsynaptic depolarization and persistently activate N-methyl-d-aspartate receptors as well as Ca(2+) influx and CaMKII and then impair LTP. 25979332 0 49 theme RECEPTOR 139:146 arg1 REGULATION 120:129 THE REGULATION 116:129 THE REGULATION OF AMPA RECEPTOR HETEROMERIZATION AND CELLULAR SIGNALING 116:186 Loss of α1,6-Fucosyltransferase Decreases Hippocampal Long Term Potentiation: IMPLICATIONS FOR CORE FUCOSYLATION IN THE REGULATION OF AMPA RECEPTOR HETEROMERIZATION AND CELLULAR SIGNALING. 25979332 7 50 theme total 1322:1326 arg1 levels 1339:1344 the total expression levels 1318:1344 the total expression levels 1318:1344 The expression levels of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors (AMPARs) in the postsynaptic density were enhanced in Fut8(-/-) mice, although there were no significant differences in the total expression levels, implicating that AMPARs without core fucosylation might exist in an active state. 25979332 7 51 theme α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate 1139:1186 arg1 receptors 1188:1196 α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors 1139:1196 α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors (AMPARs) 1139:1205 The expression levels of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors (AMPARs) in the postsynaptic density were enhanced in Fut8(-/-) mice, although there were no significant differences in the total expression levels, implicating that AMPARs without core fucosylation might exist in an active state. 25979332 7 51 theme α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate 1139:1186 arg1 AMPARs 1199:1204 AMPARs 1199:1204 AMPARs 1199:1204 The expression levels of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors (AMPARs) in the postsynaptic density were enhanced in Fut8(-/-) mice, although there were no significant differences in the total expression levels, implicating that AMPARs without core fucosylation might exist in an active state. 25979332 6 52 theme learning 1035:1042 arg1 kinase 990:995 calcium/calmodulin-dependent protein kinase II 953:998 calcium/calmodulin-dependent protein kinase II (CaMKII) 953:1007 Unexpectedly, the phosphorylation levels of calcium/calmodulin-dependent protein kinase II (CaMKII), an important mediator of learning and memory in postsynapses, were greatly increased in Fut8(-/-) mice. 25979332 6 52 theme learning 1035:1042 arg1 mediator 1023:1030 an important mediator 1010:1030 an important mediator of learning and memory in postsynapses 1010:1069 Unexpectedly, the phosphorylation levels of calcium/calmodulin-dependent protein kinase II (CaMKII), an important mediator of learning and memory in postsynapses, were greatly increased in Fut8(-/-) mice. 25979332 0 53 theme CELLULAR 169:176 arg1 SIGNALING 178:186 CELLULAR SIGNALING 169:186 CELLULAR SIGNALING 169:186 Loss of α1,6-Fucosyltransferase Decreases Hippocampal Long Term Potentiation: IMPLICATIONS FOR CORE FUCOSYLATION IN THE REGULATION OF AMPA RECEPTOR HETEROMERIZATION AND CELLULAR SIGNALING. 25979332 6 54 theme kinase 990:995 arg1 levels 943:948 the phosphorylation levels 923:948 the phosphorylation levels of calcium/calmodulin-dependent protein kinase II (CaMKII), an important mediator of learning and memory in postsynapses, 923:1070 Unexpectedly, the phosphorylation levels of calcium/calmodulin-dependent protein kinase II (CaMKII), an important mediator of learning and memory in postsynapses, were greatly increased in Fut8(-/-) mice. 25979332 0 55 theme Term 59:62 arg1 Potentiation 64:75 Hippocampal Long Term Potentiation 42:75 Hippocampal Long Term Potentiation: IMPLICATIONS FOR CORE FUCOSYLATION 42:111 Loss of α1,6-Fucosyltransferase Decreases Hippocampal Long Term Potentiation: IMPLICATIONS FOR CORE FUCOSYLATION IN THE REGULATION OF AMPA RECEPTOR HETEROMERIZATION AND CELLULAR SIGNALING. 25979332 6 56 theme phosphorylation 927:941 arg1 levels 943:948 the phosphorylation levels 923:948 the phosphorylation levels of calcium/calmodulin-dependent protein kinase II (CaMKII), an important mediator of learning and memory in postsynapses, 923:1070 Unexpectedly, the phosphorylation levels of calcium/calmodulin-dependent protein kinase II (CaMKII), an important mediator of learning and memory in postsynapses, were greatly increased in Fut8(-/-) mice. 25979332 9 57 theme N-methyl-d-aspartate 1704:1723 arg1 receptors 1725:1733 N-methyl-d-aspartate receptors 1704:1733 N-methyl-d-aspartate receptors as well as Ca(2+) influx and CaMKII 1704:1769 Taken together, loss of core fucosylation on AMPARs enhanced their heteromerization, which increase sensitivity for postsynaptic depolarization and persistently activate N-methyl-d-aspartate receptors as well as Ca(2+) influx and CaMKII and then impair LTP. 25979332 7 58 theme expression 1118:1127 arg1 levels 1129:1134 The expression levels 1114:1134 The expression levels of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors (AMPARs) in the postsynaptic density 1114:1233 The expression levels of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors (AMPARs) in the postsynaptic density were enhanced in Fut8(-/-) mice, although there were no significant differences in the total expression levels, implicating that AMPARs without core fucosylation might exist in an active state. 25979332 7 59 theme active 1415:1420 arg1 state 1422:1426 an active state 1412:1426 an active state 1412:1426 The expression levels of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors (AMPARs) in the postsynaptic density were enhanced in Fut8(-/-) mice, although there were no significant differences in the total expression levels, implicating that AMPARs without core fucosylation might exist in an active state. 25979332 4 60 theme frequency 702:710 arg1 stimulation 712:722 high frequency stimulation 697:722 high frequency stimulation 697:722 The scale of E-LTP induced by high frequency stimulation was significantly decreased in Fut8(-/-) mice. 25979332 9 61 from AMPARs 1579:1584 arg1 loss 1550:1553 loss 1550:1553 loss of core fucosylation on AMPARs 1550:1584 Taken together, loss of core fucosylation on AMPARs enhanced their heteromerization, which increase sensitivity for postsynaptic depolarization and persistently activate N-methyl-d-aspartate receptors as well as Ca(2+) influx and CaMKII and then impair LTP. 25979332 0 62 theme SIGNALING 178:186 arg1 REGULATION 120:129 THE REGULATION 116:129 THE REGULATION OF AMPA RECEPTOR HETEROMERIZATION AND CELLULAR SIGNALING 116:186 Loss of α1,6-Fucosyltransferase Decreases Hippocampal Long Term Potentiation: IMPLICATIONS FOR CORE FUCOSYLATION IN THE REGULATION OF AMPA RECEPTOR HETEROMERIZATION AND CELLULAR SIGNALING. 25979332 8 63 theme Fura-2 1479:1484 arg1 imaging 1494:1500 Fura-2 calcium imaging 1479:1500 Fura-2 calcium imaging using primary cultured neurons 1479:1531 The activation of AMPARs was further confirmed by Fura-2 calcium imaging using primary cultured neurons. 25979332 9 64 from loss 1550:1553 arg1 AMPARs 1579:1584 AMPARs 1579:1584 AMPARs 1579:1584 Taken together, loss of core fucosylation on AMPARs enhanced their heteromerization, which increase sensitivity for postsynaptic depolarization and persistently activate N-methyl-d-aspartate receptors as well as Ca(2+) influx and CaMKII and then impair LTP. 25979332 4 65 theme high 697:700 arg1 frequency 702:710 high frequency 697:710 high frequency stimulation 697:722 The scale of E-LTP induced by high frequency stimulation was significantly decreased in Fut8(-/-) mice. 25979332 6 66 theme Fut8 1098:1101 arg1 mice 1108:1111 Fut8(-/-) mice 1098:1111 Fut8(-/-) mice 1098:1111 Unexpectedly, the phosphorylation levels of calcium/calmodulin-dependent protein kinase II (CaMKII), an important mediator of learning and memory in postsynapses, were greatly increased in Fut8(-/-) mice. 25979332 6 67 from mediator 1023:1030 arg1 postsynapses 1058:1069 postsynapses 1058:1069 postsynapses 1058:1069 Unexpectedly, the phosphorylation levels of calcium/calmodulin-dependent protein kinase II (CaMKII), an important mediator of learning and memory in postsynapses, were greatly increased in Fut8(-/-) mice. 25979332 8 68 theme AMPARs 1447:1452 arg1 activation 1433:1442 The activation 1429:1442 The activation of AMPARs 1429:1452 The activation of AMPARs was further confirmed by Fura-2 calcium imaging using primary cultured neurons. 25979332 2 69 theme Fut8-knock-out 390:403 arg1 mice 417:420 Fut8-knock-out (Fut8(-/-)) mice 390:420 Fut8-knock-out (Fut8(-/-)) mice 390:420 We previously reported that Fut8-knock-out (Fut8(-/-)) mice showed a schizophrenia-like phenotype and a decrease in working memory. 25979332 9 70 from fucosylation 1563:1574 arg1 AMPARs 1579:1584 AMPARs 1579:1584 AMPARs 1579:1584 Taken together, loss of core fucosylation on AMPARs enhanced their heteromerization, which increase sensitivity for postsynaptic depolarization and persistently activate N-methyl-d-aspartate receptors as well as Ca(2+) influx and CaMKII and then impair LTP. 25979332 6 71 theme important 1013:1021 arg1 kinase 990:995 calcium/calmodulin-dependent protein kinase II 953:998 calcium/calmodulin-dependent protein kinase II (CaMKII) 953:1007 Unexpectedly, the phosphorylation levels of calcium/calmodulin-dependent protein kinase II (CaMKII), an important mediator of learning and memory in postsynapses, were greatly increased in Fut8(-/-) mice. 25979332 6 71 theme important 1013:1021 arg1 mediator 1023:1030 an important mediator 1010:1030 an important mediator of learning and memory in postsynapses 1010:1069 Unexpectedly, the phosphorylation levels of calcium/calmodulin-dependent protein kinase II (CaMKII), an important mediator of learning and memory in postsynapses, were greatly increased in Fut8(-/-) mice. 25979332 5 72 theme significant 812:822 arg1 differences 824:834 no significant differences 809:834 no significant differences 809:834 Tetraethylammonium-induced LTP showed no significant differences, suggesting that the decline in E-LTP was caused by postsynaptic events. 25979332 0 73 dep RECEPTOR 139:146 arg1 HETEROMERIZATION 148:163 HETEROMERIZATION 148:163 HETEROMERIZATION 148:163 Loss of α1,6-Fucosyltransferase Decreases Hippocampal Long Term Potentiation: IMPLICATIONS FOR CORE FUCOSYLATION IN THE REGULATION OF AMPA RECEPTOR HETEROMERIZATION AND CELLULAR SIGNALING. 25979332 7 74 theme Fut8 1252:1255 arg1 mice 1262:1265 Fut8(-/-) mice 1252:1265 Fut8(-/-) mice 1252:1265 The expression levels of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors (AMPARs) in the postsynaptic density were enhanced in Fut8(-/-) mice, although there were no significant differences in the total expression levels, implicating that AMPARs without core fucosylation might exist in an active state. 25979332 7 75 theme postsynaptic 1214:1225 arg1 density 1227:1233 the postsynaptic density 1210:1233 the postsynaptic density 1210:1233 The expression levels of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors (AMPARs) in the postsynaptic density were enhanced in Fut8(-/-) mice, although there were no significant differences in the total expression levels, implicating that AMPARs without core fucosylation might exist in an active state. 28766587 0 0 theme inhibitor 98:106 arg1 high-affinity 37:49 high-affinity 37:49 high-affinity 37:49 An atypical interaction explains the high-affinity of a non-hydrolyzable S-linked 1,6-α-mannanase inhibitor. 28766587 2 1 with interaction 364:374 arg1 acid/base 423:431 the catalytic acid/base 409:431 the catalytic acid/base 409:431 X-ray crystallography showed an atypical interaction of the isofagomine nitrogen with the catalytic acid/base. 28766587 0 2 theme 1,6-α-mannanase 82:96 arg1 inhibitor 98:106 a non-hydrolyzable S-linked 1,6-α-mannanase inhibitor 54:106 a non-hydrolyzable S-linked 1,6-α-mannanase inhibitor 54:106 An atypical interaction explains the high-affinity of a non-hydrolyzable S-linked 1,6-α-mannanase inhibitor. 28766587 2 3 theme catalytic 413:421 arg1 acid/base 423:431 the catalytic acid/base 409:431 the catalytic acid/base 409:431 X-ray crystallography showed an atypical interaction of the isofagomine nitrogen with the catalytic acid/base. 28766587 2 4 theme atypical 355:362 arg1 interaction 364:374 an atypical interaction 352:374 an atypical interaction of the isofagomine nitrogen with the catalytic acid/base 352:431 X-ray crystallography showed an atypical interaction of the isofagomine nitrogen with the catalytic acid/base. 28766587 3 5 theme Molecular 434:442 arg1 simulations 453:463 Molecular dynamics simulations 434:463 Molecular dynamics simulations 434:463 Molecular dynamics simulations reveal that the atypical binding results from sulfur perturbing the most stable form away from the nucleophile interaction preferred for the O-linked congener. 28766587 2 6 theme X-ray 323:327 arg1 crystallography 329:343 X-ray crystallography 323:343 X-ray crystallography 323:343 X-ray crystallography showed an atypical interaction of the isofagomine nitrogen with the catalytic acid/base. 28766587 0 7 theme atypical 3:10 arg1 interaction 12:22 An atypical interaction 0:22 An atypical interaction 0:22 An atypical interaction explains the high-affinity of a non-hydrolyzable S-linked 1,6-α-mannanase inhibitor. 28766587 3 8 theme dynamics 444:451 arg1 simulations 453:463 Molecular dynamics simulations 434:463 Molecular dynamics simulations 434:463 Molecular dynamics simulations reveal that the atypical binding results from sulfur perturbing the most stable form away from the nucleophile interaction preferred for the O-linked congener. 28766587 1 9 from circulans 312:320 arg1 endo-1,6-α-mannanase 277:296 a family 76 endo-1,6-α-mannanase 265:296 a family 76 endo-1,6-α-mannanase from Bacillus circulans 265:320 The non-hydrolyzable S-linked azasugars, 1,6-α-mannosylthio- and 1,6-α-mannobiosylthioisofagomine, were synthesized and shown to bind with high affinity to a family 76 endo-1,6-α-mannanase from Bacillus circulans. 28766587 1 10 theme non-hydrolyzable 113:128 arg1 1,6-α-mannosylthio- 150:168 1,6-α-mannosylthio- 150:168 1,6-α-mannosylthio- 150:168 The non-hydrolyzable S-linked azasugars, 1,6-α-mannosylthio- and 1,6-α-mannobiosylthioisofagomine, were synthesized and shown to bind with high affinity to a family 76 endo-1,6-α-mannanase from Bacillus circulans. 28766587 1 10 theme non-hydrolyzable 113:128 arg1 azasugars 139:147 The non-hydrolyzable S-linked azasugars 109:147 The non-hydrolyzable S-linked azasugars 109:147 The non-hydrolyzable S-linked azasugars, 1,6-α-mannosylthio- and 1,6-α-mannobiosylthioisofagomine, were synthesized and shown to bind with high affinity to a family 76 endo-1,6-α-mannanase from Bacillus circulans. 28766587 1 10 theme non-hydrolyzable 113:128 arg1 1,6-α-mannobiosylthioisofagomine 174:205 1,6-α-mannobiosylthioisofagomine 174:205 1,6-α-mannobiosylthioisofagomine 174:205 The non-hydrolyzable S-linked azasugars, 1,6-α-mannosylthio- and 1,6-α-mannobiosylthioisofagomine, were synthesized and shown to bind with high affinity to a family 76 endo-1,6-α-mannanase from Bacillus circulans. 28766587 1 11 theme S-linked 130:137 arg1 1,6-α-mannosylthio- 150:168 1,6-α-mannosylthio- 150:168 1,6-α-mannosylthio- 150:168 The non-hydrolyzable S-linked azasugars, 1,6-α-mannosylthio- and 1,6-α-mannobiosylthioisofagomine, were synthesized and shown to bind with high affinity to a family 76 endo-1,6-α-mannanase from Bacillus circulans. 28766587 1 11 theme S-linked 130:137 arg1 azasugars 139:147 The non-hydrolyzable S-linked azasugars 109:147 The non-hydrolyzable S-linked azasugars 109:147 The non-hydrolyzable S-linked azasugars, 1,6-α-mannosylthio- and 1,6-α-mannobiosylthioisofagomine, were synthesized and shown to bind with high affinity to a family 76 endo-1,6-α-mannanase from Bacillus circulans. 28766587 1 11 theme S-linked 130:137 arg1 1,6-α-mannobiosylthioisofagomine 174:205 1,6-α-mannobiosylthioisofagomine 174:205 1,6-α-mannobiosylthioisofagomine 174:205 The non-hydrolyzable S-linked azasugars, 1,6-α-mannosylthio- and 1,6-α-mannobiosylthioisofagomine, were synthesized and shown to bind with high affinity to a family 76 endo-1,6-α-mannanase from Bacillus circulans. 28766587 1 12 theme high 248:251 arg1 affinity 253:260 high affinity 248:260 high affinity 248:260 The non-hydrolyzable S-linked azasugars, 1,6-α-mannosylthio- and 1,6-α-mannobiosylthioisofagomine, were synthesized and shown to bind with high affinity to a family 76 endo-1,6-α-mannanase from Bacillus circulans. 28766587 3 13 link O-linked 606:613 arg1 congener 615:622 the O-linked congener 602:622 the O-linked congener 602:622 Molecular dynamics simulations reveal that the atypical binding results from sulfur perturbing the most stable form away from the nucleophile interaction preferred for the O-linked congener. 28766587 3 14 theme stable 538:543 arg1 form 545:548 the most stable form 529:548 the most stable form away from the nucleophile interaction preferred for the O-linked congener 529:622 Molecular dynamics simulations reveal that the atypical binding results from sulfur perturbing the most stable form away from the nucleophile interaction preferred for the O-linked congener. 28766587 0 15 theme non-hydrolyzable 56:71 arg1 inhibitor 98:106 a non-hydrolyzable S-linked 1,6-α-mannanase inhibitor 54:106 a non-hydrolyzable S-linked 1,6-α-mannanase inhibitor 54:106 An atypical interaction explains the high-affinity of a non-hydrolyzable S-linked 1,6-α-mannanase inhibitor. 28766587 3 16 theme nucleophile 564:574 arg1 interaction 576:586 the nucleophile interaction 560:586 the nucleophile interaction 560:586 Molecular dynamics simulations reveal that the atypical binding results from sulfur perturbing the most stable form away from the nucleophile interaction preferred for the O-linked congener. 28766587 3 17 theme atypical 481:488 arg1 binding 490:496 the atypical binding 477:496 the atypical binding 477:496 Molecular dynamics simulations reveal that the atypical binding results from sulfur perturbing the most stable form away from the nucleophile interaction preferred for the O-linked congener. 28766587 0 18 link S-linked 73:80 arg1 inhibitor 98:106 a non-hydrolyzable S-linked 1,6-α-mannanase inhibitor 54:106 a non-hydrolyzable S-linked 1,6-α-mannanase inhibitor 54:106 An atypical interaction explains the high-affinity of a non-hydrolyzable S-linked 1,6-α-mannanase inhibitor. 28766587 2 19 theme nitrogen 395:402 arg1 interaction 364:374 an atypical interaction 352:374 an atypical interaction of the isofagomine nitrogen with the catalytic acid/base 352:431 X-ray crystallography showed an atypical interaction of the isofagomine nitrogen with the catalytic acid/base. 28766587 2 20 theme isofagomine 383:393 arg1 nitrogen 395:402 the isofagomine nitrogen 379:402 the isofagomine nitrogen 379:402 X-ray crystallography showed an atypical interaction of the isofagomine nitrogen with the catalytic acid/base. 28766587 1 21 theme family 267:272 arg1 endo-1,6-α-mannanase 277:296 a family 76 endo-1,6-α-mannanase 265:296 a family 76 endo-1,6-α-mannanase from Bacillus circulans 265:320 The non-hydrolyzable S-linked azasugars, 1,6-α-mannosylthio- and 1,6-α-mannobiosylthioisofagomine, were synthesized and shown to bind with high affinity to a family 76 endo-1,6-α-mannanase from Bacillus circulans. 28766587 0 22 theme S-linked 73:80 arg1 inhibitor 98:106 a non-hydrolyzable S-linked 1,6-α-mannanase inhibitor 54:106 a non-hydrolyzable S-linked 1,6-α-mannanase inhibitor 54:106 An atypical interaction explains the high-affinity of a non-hydrolyzable S-linked 1,6-α-mannanase inhibitor. 28766587 1 23 link S-linked 130:137 arg1 1,6-α-mannosylthio- 150:168 1,6-α-mannosylthio- 150:168 1,6-α-mannosylthio- 150:168 The non-hydrolyzable S-linked azasugars, 1,6-α-mannosylthio- and 1,6-α-mannobiosylthioisofagomine, were synthesized and shown to bind with high affinity to a family 76 endo-1,6-α-mannanase from Bacillus circulans. 28766587 1 23 link S-linked 130:137 arg1 azasugars 139:147 The non-hydrolyzable S-linked azasugars 109:147 The non-hydrolyzable S-linked azasugars 109:147 The non-hydrolyzable S-linked azasugars, 1,6-α-mannosylthio- and 1,6-α-mannobiosylthioisofagomine, were synthesized and shown to bind with high affinity to a family 76 endo-1,6-α-mannanase from Bacillus circulans. 28766587 1 23 link S-linked 130:137 arg1 1,6-α-mannobiosylthioisofagomine 174:205 1,6-α-mannobiosylthioisofagomine 174:205 1,6-α-mannobiosylthioisofagomine 174:205 The non-hydrolyzable S-linked azasugars, 1,6-α-mannosylthio- and 1,6-α-mannobiosylthioisofagomine, were synthesized and shown to bind with high affinity to a family 76 endo-1,6-α-mannanase from Bacillus circulans. 28766587 3 24 theme O-linked 606:613 arg1 congener 615:622 the O-linked congener 602:622 the O-linked congener 602:622 Molecular dynamics simulations reveal that the atypical binding results from sulfur perturbing the most stable form away from the nucleophile interaction preferred for the O-linked congener. 28352258 5 0 theme nasal 1003:1007 arg1 secretions 1009:1018 nasal secretions 1003:1018 nasal secretions 1003:1018 As a part of the National Epidemiological Surveillance of Infectious Diseases, Japan, 1308 clinical specimens (throat swabs, nasal swabs, nasal secretions, and nasal aspirate fluids) collected at 24 hospitals or clinics in Yokohama City were screened for 15 major respiratory viruses with a multiplex reverse transcription-PCR assay. 28352258 11 1 from spread 2157:2162 arg1 community 2171:2179 the community 2167:2179 the community 2167:2179 The detailed mechanism by which the A2b180nt-dup HMPV strains gained an advantage that allowed their efficient spread in the community and the effects of 60aa-dup on HMPV virulence must be clarified. 28352258 6 2 theme genes 1316:1320 arg1 sequences 1297:1305 the nucleotide sequences 1282:1305 the nucleotide sequences of the G genes of 84 HMPV strains 1282:1339 HMPV was detected in 91 specimens, accounting for 7.0% of the total specimens, and the nucleotide sequences of the G genes of 84 HMPV strains were determined. 28352258 11 3 theme 60aa-dup 2200:2207 arg1 mechanism 2059:2067 The detailed mechanism 2046:2067 The detailed mechanism by which the A2b180nt-dup HMPV strains gained an advantage that allowed their efficient spread in the community 2046:2179 The detailed mechanism by which the A2b180nt-dup HMPV strains gained an advantage that allowed their efficient spread in the community and the effects of 60aa-dup on HMPV virulence must be clarified. 28352258 11 3 theme 60aa-dup 2200:2207 arg1 effects 2189:2195 the effects 2185:2195 the effects of 60aa-dup on HMPV virulence 2185:2225 The detailed mechanism by which the A2b180nt-dup HMPV strains gained an advantage that allowed their efficient spread in the community and the effects of 60aa-dup on HMPV virulence must be clarified. 28352258 3 4 theme behavior 515:522 arg1 understanding 485:497 our understanding 481:497 our understanding of the epidemic behavior of the virus 481:535 Molecular epidemiological, genetic, and antigenetic evolutionary studies of HMPV will strengthen our understanding of the epidemic behavior of the virus and provide valuable insight for the control of HMPV and the development of vaccines and antiviral drugs against HMPV infection. 28352258 5 5 from Surveillance 907:918 arg1 City 1097:1100 City 1097:1100 City 1097:1100 As a part of the National Epidemiological Surveillance of Infectious Diseases, Japan, 1308 clinical specimens (throat swabs, nasal swabs, nasal secretions, and nasal aspirate fluids) collected at 24 hospitals or clinics in Yokohama City were screened for 15 major respiratory viruses with a multiplex reverse transcription-PCR assay. 28352258 8 6 from duplication 1565:1575 arg1 gene 1598:1601 the G gene 1592:1601 the G gene 1592:1601 Approximately half the HMPV A2b subgroup strains detected since 2014 had a 180-nucleotide duplication (180nt-dup) in the G gene and clustered on a phylogenic tree with four classical 180nt-dup-lacking HMPV A2b strains prevalent between 2014 and 2015. 28352258 8 7 theme 180nt-dup-lacking 1658:1674 arg1 strains 1685:1691 four classical 180nt-dup-lacking HMPV A2b strains 1643:1691 four classical 180nt-dup-lacking HMPV A2b strains prevalent between 2014 and 2015 1643:1723 Approximately half the HMPV A2b subgroup strains detected since 2014 had a 180-nucleotide duplication (180nt-dup) in the G gene and clustered on a phylogenic tree with four classical 180nt-dup-lacking HMPV A2b strains prevalent between 2014 and 2015. 28352258 8 8 theme subgroup 1507:1514 arg1 strains 1516:1522 the HMPV A2b subgroup strains 1494:1522 half the HMPV A2b subgroup strains detected since 2014 1489:1542 Approximately half the HMPV A2b subgroup strains detected since 2014 had a 180-nucleotide duplication (180nt-dup) in the G gene and clustered on a phylogenic tree with four classical 180nt-dup-lacking HMPV A2b strains prevalent between 2014 and 2015. 28352258 2 9 from agent 312:316 arg1 humans 353:358 humans 353:358 humans 353:358 Seroepidemiological studies have shown that HMPV has been a major etiological agent of acute respiratory infections in humans for more than 50 years. 28352258 8 10 theme A2b 1681:1683 arg1 strains 1685:1691 four classical 180nt-dup-lacking HMPV A2b strains 1643:1691 four classical 180nt-dup-lacking HMPV A2b strains prevalent between 2014 and 2015 1643:1723 Approximately half the HMPV A2b subgroup strains detected since 2014 had a 180-nucleotide duplication (180nt-dup) in the G gene and clustered on a phylogenic tree with four classical 180nt-dup-lacking HMPV A2b strains prevalent between 2014 and 2015. 28352258 10 11 theme epidemic 2013:2020 arg1 strains 2022:2028 major epidemic strains 2007:2028 major epidemic strains 2007:2028 Our data suggest that 180nt-dup occurred between 2011 and 2013 and that HMPV A2b strains with 180nt-dup (A2b180nt-dup HMPV) became major epidemic strains within 3 years. 28352258 5 12 from City 1097:1100 arg1 Surveillance 907:918 the National Epidemiological Surveillance 878:918 the National Epidemiological Surveillance of Infectious Diseases, Japan, 1308 clinical specimens (throat swabs, nasal swabs, nasal secretions, and nasal aspirate fluids) collected at 24 hospitals or clinics in Yokohama City 878:1100 As a part of the National Epidemiological Surveillance of Infectious Diseases, Japan, 1308 clinical specimens (throat swabs, nasal swabs, nasal secretions, and nasal aspirate fluids) collected at 24 hospitals or clinics in Yokohama City were screened for 15 major respiratory viruses with a multiplex reverse transcription-PCR assay. 28352258 3 13 theme Molecular 384:392 arg1 studies 449:455 Molecular epidemiological, genetic, and antigenetic evolutionary studies 384:455 Molecular epidemiological, genetic, and antigenetic evolutionary studies of HMPV 384:463 Molecular epidemiological, genetic, and antigenetic evolutionary studies of HMPV will strengthen our understanding of the epidemic behavior of the virus and provide valuable insight for the control of HMPV and the development of vaccines and antiviral drugs against HMPV infection. 28352258 11 14 from mechanism 2059:2067 arg1 virulence 2217:2225 HMPV virulence 2212:2225 HMPV virulence 2212:2225 The detailed mechanism by which the A2b180nt-dup HMPV strains gained an advantage that allowed their efficient spread in the community and the effects of 60aa-dup on HMPV virulence must be clarified. 28352258 10 15 theme HMPV 1948:1951 arg1 strains 1957:1963 HMPV A2b strains 1948:1963 HMPV A2b strains with 180nt-dup (A2b180nt-dup HMPV) 1948:1998 Our data suggest that 180nt-dup occurred between 2011 and 2013 and that HMPV A2b strains with 180nt-dup (A2b180nt-dup HMPV) became major epidemic strains within 3 years. 28352258 3 16 theme valuable 549:556 arg1 insight 558:564 valuable insight 549:564 valuable insight for the control of HMPV 549:588 Molecular epidemiological, genetic, and antigenetic evolutionary studies of HMPV will strengthen our understanding of the epidemic behavior of the virus and provide valuable insight for the control of HMPV and the development of vaccines and antiviral drugs against HMPV infection. 28352258 10 17 theme major 2007:2011 arg1 strains 2022:2028 major epidemic strains 2007:2028 major epidemic strains 2007:2028 Our data suggest that 180nt-dup occurred between 2011 and 2013 and that HMPV A2b strains with 180nt-dup (A2b180nt-dup HMPV) became major epidemic strains within 3 years. 28352258 5 18 theme multiplex 1156:1164 arg1 assay 1192:1196 a multiplex reverse transcription-PCR assay 1154:1196 a multiplex reverse transcription-PCR assay 1154:1196 As a part of the National Epidemiological Surveillance of Infectious Diseases, Japan, 1308 clinical specimens (throat swabs, nasal swabs, nasal secretions, and nasal aspirate fluids) collected at 24 hospitals or clinics in Yokohama City were screened for 15 major respiratory viruses with a multiplex reverse transcription-PCR assay. 28352258 5 19 theme clinical 956:963 arg1 specimens 965:973 1308 clinical specimens 951:973 1308 clinical specimens (throat swabs, nasal swabs, nasal secretions, and nasal aspirate fluids) collected at 24 hospitals 951:1072 As a part of the National Epidemiological Surveillance of Infectious Diseases, Japan, 1308 clinical specimens (throat swabs, nasal swabs, nasal secretions, and nasal aspirate fluids) collected at 24 hospitals or clinics in Yokohama City were screened for 15 major respiratory viruses with a multiplex reverse transcription-PCR assay. 28352258 3 20 theme HMPV 585:588 arg1 control 574:580 the control 570:580 the control of HMPV 570:588 Molecular epidemiological, genetic, and antigenetic evolutionary studies of HMPV will strengthen our understanding of the epidemic behavior of the virus and provide valuable insight for the control of HMPV and the development of vaccines and antiviral drugs against HMPV infection. 28352258 0 21 from Circulating 87:97 arg1 Japan 117:121 Japan 117:121 Japan 117:121 180-Nucleotide Duplication in the G Gene of Human metapneumovirus A2b Subgroup Strains Circulating in Yokohama City, Japan, since 2014. 28352258 5 22 theme transcription-PCR 1174:1190 arg1 assay 1192:1196 a multiplex reverse transcription-PCR assay 1154:1196 a multiplex reverse transcription-PCR assay 1154:1196 As a part of the National Epidemiological Surveillance of Infectious Diseases, Japan, 1308 clinical specimens (throat swabs, nasal swabs, nasal secretions, and nasal aspirate fluids) collected at 24 hospitals or clinics in Yokohama City were screened for 15 major respiratory viruses with a multiplex reverse transcription-PCR assay. 28352258 5 23 from specimens 965:973 arg1 City 1097:1100 City 1097:1100 City 1097:1100 As a part of the National Epidemiological Surveillance of Infectious Diseases, Japan, 1308 clinical specimens (throat swabs, nasal swabs, nasal secretions, and nasal aspirate fluids) collected at 24 hospitals or clinics in Yokohama City were screened for 15 major respiratory viruses with a multiplex reverse transcription-PCR assay. 28352258 5 24 with viruses 1141:1147 arg1 assay 1192:1196 a multiplex reverse transcription-PCR assay 1154:1196 a multiplex reverse transcription-PCR assay 1154:1196 As a part of the National Epidemiological Surveillance of Infectious Diseases, Japan, 1308 clinical specimens (throat swabs, nasal swabs, nasal secretions, and nasal aspirate fluids) collected at 24 hospitals or clinics in Yokohama City were screened for 15 major respiratory viruses with a multiplex reverse transcription-PCR assay. 28352258 4 25 dep variations 720:729 arg1 genetic 712:718 genetic 712:718 genetic 712:718 In this study, the nucleotide sequence of and genetic variations in the G gene were analyzed in HMPV strains prevalent in Yokohama City, in the Kanto area, Japan, between January 2013 and June 2016. 28352258 11 26 theme HMPV 2212:2215 arg1 virulence 2217:2225 HMPV virulence 2212:2225 HMPV virulence 2212:2225 The detailed mechanism by which the A2b180nt-dup HMPV strains gained an advantage that allowed their efficient spread in the community and the effects of 60aa-dup on HMPV virulence must be clarified. 28352258 5 27 theme respiratory 1129:1139 arg1 viruses 1141:1147 15 major respiratory viruses 1120:1147 15 major respiratory viruses with a multiplex reverse transcription-PCR assay 1120:1196 As a part of the National Epidemiological Surveillance of Infectious Diseases, Japan, 1308 clinical specimens (throat swabs, nasal swabs, nasal secretions, and nasal aspirate fluids) collected at 24 hospitals or clinics in Yokohama City were screened for 15 major respiratory viruses with a multiplex reverse transcription-PCR assay. 28352258 0 28 theme Subgroup 70:77 arg1 Strains 79:85 Human metapneumovirus A2b Subgroup Strains 44:85 Human metapneumovirus A2b Subgroup Strains 44:85 180-Nucleotide Duplication in the G Gene of Human metapneumovirus A2b Subgroup Strains Circulating in Yokohama City, Japan, since 2014. 28352258 8 29 theme G 1596:1596 arg1 gene 1598:1601 the G gene 1592:1601 the G gene 1592:1601 Approximately half the HMPV A2b subgroup strains detected since 2014 had a 180-nucleotide duplication (180nt-dup) in the G gene and clustered on a phylogenic tree with four classical 180nt-dup-lacking HMPV A2b strains prevalent between 2014 and 2015. 28352258 6 30 located detected 1208:1215 arg2 HMPV 1199:1202 HMPV 1199:1202 HMPV 1199:1202 HMPV was detected in 91 specimens, accounting for 7.0% of the total specimens, and the nucleotide sequences of the G genes of 84 HMPV strains were determined. 28352258 6 30 located detected 1208:1215 arg1 specimens 1223:1231 91 specimens 1220:1231 91 specimens 1220:1231 HMPV was detected in 91 specimens, accounting for 7.0% of the total specimens, and the nucleotide sequences of the G genes of 84 HMPV strains were determined. 28352258 9 31 theme G 1793:1793 arg1 protein 1795:1801 the G protein 1789:1801 the G protein 1789:1801 The 180nt-dup causes a 60-amino-acid duplication (60aa-dup) in the G protein, creating 23-25 additional potential acceptor sites for O-linked sugars. 28352258 5 32 theme nasal 990:994 arg1 swabs 996:1000 nasal swabs 990:1000 nasal swabs 990:1000 As a part of the National Epidemiological Surveillance of Infectious Diseases, Japan, 1308 clinical specimens (throat swabs, nasal swabs, nasal secretions, and nasal aspirate fluids) collected at 24 hospitals or clinics in Yokohama City were screened for 15 major respiratory viruses with a multiplex reverse transcription-PCR assay. 28352258 8 33 theme HMPV 1498:1501 arg1 strains 1516:1522 the HMPV A2b subgroup strains 1494:1522 half the HMPV A2b subgroup strains detected since 2014 1489:1542 Approximately half the HMPV A2b subgroup strains detected since 2014 had a 180-nucleotide duplication (180nt-dup) in the G gene and clustered on a phylogenic tree with four classical 180nt-dup-lacking HMPV A2b strains prevalent between 2014 and 2015. 28352258 10 34 theme A2b180nt-dup 1981:1992 arg1 180nt-dup 1970:1978 180nt-dup 1970:1978 180nt-dup (A2b180nt-dup HMPV) 1970:1998 Our data suggest that 180nt-dup occurred between 2011 and 2013 and that HMPV A2b strains with 180nt-dup (A2b180nt-dup HMPV) became major epidemic strains within 3 years. 28352258 10 34 theme A2b180nt-dup 1981:1992 arg1 HMPV 1994:1997 A2b180nt-dup HMPV 1981:1997 A2b180nt-dup HMPV 1981:1997 Our data suggest that 180nt-dup occurred between 2011 and 2013 and that HMPV A2b strains with 180nt-dup (A2b180nt-dup HMPV) became major epidemic strains within 3 years. 28352258 3 35 theme epidemiological 394:408 arg1 studies 449:455 Molecular epidemiological, genetic, and antigenetic evolutionary studies 384:455 Molecular epidemiological, genetic, and antigenetic evolutionary studies of HMPV 384:463 Molecular epidemiological, genetic, and antigenetic evolutionary studies of HMPV will strengthen our understanding of the epidemic behavior of the virus and provide valuable insight for the control of HMPV and the development of vaccines and antiviral drugs against HMPV infection. 28352258 7 36 dep subgroups 1429:1437 arg1 B2 1457:1458 B2 1457:1458 B2 1457:1458 Among these 84 strains, 6, 43, 10, and 25 strains were classified into subgroups A2a, A2b, B1, and B2, respectively. 28352258 7 36 dep subgroups 1429:1437 arg1 A2b 1444:1446 A2b 1444:1446 A2b 1444:1446 Among these 84 strains, 6, 43, 10, and 25 strains were classified into subgroups A2a, A2b, B1, and B2, respectively. 28352258 7 36 dep subgroups 1429:1437 arg1 A2a 1439:1441 A2a 1439:1441 A2a 1439:1441 Among these 84 strains, 6, 43, 10, and 25 strains were classified into subgroups A2a, A2b, B1, and B2, respectively. 28352258 7 36 dep subgroups 1429:1437 arg1 subgroups 1429:1437 subgroups A2a, A2b, B1, and B2 1429:1458 subgroups A2a, A2b, B1, and B2 1429:1458 Among these 84 strains, 6, 43, 10, and 25 strains were classified into subgroups A2a, A2b, B1, and B2, respectively. 28352258 7 36 dep subgroups 1429:1437 arg1 B1 1449:1450 B1 1449:1450 B1 1449:1450 Among these 84 strains, 6, 43, 10, and 25 strains were classified into subgroups A2a, A2b, B1, and B2, respectively. 28352258 0 37 theme A2b 66:68 arg1 Strains 79:85 Human metapneumovirus A2b Subgroup Strains 44:85 Human metapneumovirus A2b Subgroup Strains 44:85 180-Nucleotide Duplication in the G Gene of Human metapneumovirus A2b Subgroup Strains Circulating in Yokohama City, Japan, since 2014. 28352258 4 38 theme nucleotide 685:694 arg1 sequence 696:703 the nucleotide sequence 681:703 the nucleotide sequence of and genetic variations in the G gene 681:743 In this study, the nucleotide sequence of and genetic variations in the G gene were analyzed in HMPV strains prevalent in Yokohama City, in the Kanto area, Japan, between January 2013 and June 2016. 28352258 8 39 with tree 1633:1636 arg1 strains 1685:1691 four classical 180nt-dup-lacking HMPV A2b strains 1643:1691 four classical 180nt-dup-lacking HMPV A2b strains prevalent between 2014 and 2015 1643:1723 Approximately half the HMPV A2b subgroup strains detected since 2014 had a 180-nucleotide duplication (180nt-dup) in the G gene and clustered on a phylogenic tree with four classical 180nt-dup-lacking HMPV A2b strains prevalent between 2014 and 2015. 28352258 0 40 theme 180-Nucleotide 0:13 arg1 Duplication 15:25 180-Nucleotide Duplication 0:25 180-Nucleotide Duplication in the G Gene of Human metapneumovirus A2b Subgroup Strains 0:85 180-Nucleotide Duplication in the G Gene of Human metapneumovirus A2b Subgroup Strains Circulating in Yokohama City, Japan, since 2014. 28352258 8 41 theme phylogenic 1622:1631 arg1 tree 1633:1636 a phylogenic tree 1620:1636 a phylogenic tree with four classical 180nt-dup-lacking HMPV A2b strains prevalent between 2014 and 2015 1620:1723 Approximately half the HMPV A2b subgroup strains detected since 2014 had a 180-nucleotide duplication (180nt-dup) in the G gene and clustered on a phylogenic tree with four classical 180nt-dup-lacking HMPV A2b strains prevalent between 2014 and 2015. 28352258 9 42 theme potential 1830:1838 arg1 sites 1849:1853 23-25 additional potential acceptor sites 1813:1853 23-25 additional potential acceptor sites for O-linked sugars 1813:1873 The 180nt-dup causes a 60-amino-acid duplication (60aa-dup) in the G protein, creating 23-25 additional potential acceptor sites for O-linked sugars. 28352258 6 43 theme nucleotide 1286:1295 arg1 sequences 1297:1305 the nucleotide sequences 1282:1305 the nucleotide sequences of the G genes of 84 HMPV strains 1282:1339 HMPV was detected in 91 specimens, accounting for 7.0% of the total specimens, and the nucleotide sequences of the G genes of 84 HMPV strains were determined. 28352258 9 44 from duplication 1763:1773 arg1 protein 1795:1801 the G protein 1789:1801 the G protein 1789:1801 The 180nt-dup causes a 60-amino-acid duplication (60aa-dup) in the G protein, creating 23-25 additional potential acceptor sites for O-linked sugars. 28352258 3 45 theme genetic 411:417 arg1 studies 449:455 Molecular epidemiological, genetic, and antigenetic evolutionary studies 384:455 Molecular epidemiological, genetic, and antigenetic evolutionary studies of HMPV 384:463 Molecular epidemiological, genetic, and antigenetic evolutionary studies of HMPV will strengthen our understanding of the epidemic behavior of the virus and provide valuable insight for the control of HMPV and the development of vaccines and antiviral drugs against HMPV infection. 28352258 0 46 theme G 34:34 arg1 Gene 36:39 the G Gene 30:39 the G Gene 30:39 180-Nucleotide Duplication in the G Gene of Human metapneumovirus A2b Subgroup Strains Circulating in Yokohama City, Japan, since 2014. 28352258 5 47 theme aspirate 1031:1038 arg1 fluids 1040:1045 nasal aspirate fluids 1025:1045 nasal aspirate fluids 1025:1045 As a part of the National Epidemiological Surveillance of Infectious Diseases, Japan, 1308 clinical specimens (throat swabs, nasal swabs, nasal secretions, and nasal aspirate fluids) collected at 24 hospitals or clinics in Yokohama City were screened for 15 major respiratory viruses with a multiplex reverse transcription-PCR assay. 28352258 10 48 with strains 1957:1963 arg1 180nt-dup 1970:1978 180nt-dup 1970:1978 180nt-dup (A2b180nt-dup HMPV) 1970:1998 Our data suggest that 180nt-dup occurred between 2011 and 2013 and that HMPV A2b strains with 180nt-dup (A2b180nt-dup HMPV) became major epidemic strains within 3 years. 28352258 10 48 with strains 1957:1963 arg1 HMPV 1994:1997 A2b180nt-dup HMPV 1981:1997 A2b180nt-dup HMPV 1981:1997 Our data suggest that 180nt-dup occurred between 2011 and 2013 and that HMPV A2b strains with 180nt-dup (A2b180nt-dup HMPV) became major epidemic strains within 3 years. 28352258 5 49 theme Diseases 934:941 arg1 Surveillance 907:918 the National Epidemiological Surveillance 878:918 the National Epidemiological Surveillance of Infectious Diseases, Japan, 1308 clinical specimens (throat swabs, nasal swabs, nasal secretions, and nasal aspirate fluids) collected at 24 hospitals or clinics in Yokohama City 878:1100 As a part of the National Epidemiological Surveillance of Infectious Diseases, Japan, 1308 clinical specimens (throat swabs, nasal swabs, nasal secretions, and nasal aspirate fluids) collected at 24 hospitals or clinics in Yokohama City were screened for 15 major respiratory viruses with a multiplex reverse transcription-PCR assay. 28352258 0 50 theme metapneumovirus 50:64 arg1 Strains 79:85 Human metapneumovirus A2b Subgroup Strains 44:85 Human metapneumovirus A2b Subgroup Strains 44:85 180-Nucleotide Duplication in the G Gene of Human metapneumovirus A2b Subgroup Strains Circulating in Yokohama City, Japan, since 2014. 28352258 2 51 theme etiological 300:310 arg1 HMPV 278:281 HMPV 278:281 HMPV 278:281 Seroepidemiological studies have shown that HMPV has been a major etiological agent of acute respiratory infections in humans for more than 50 years. 28352258 2 51 theme etiological 300:310 arg1 agent 312:316 a major etiological agent 292:316 a major etiological agent of acute respiratory infections in humans for more than 50 years 292:381 Seroepidemiological studies have shown that HMPV has been a major etiological agent of acute respiratory infections in humans for more than 50 years. 28352258 6 52 theme specimens 1267:1275 arg1 specimens 1267:1275 the total specimens 1257:1275 the total specimens 1257:1275 HMPV was detected in 91 specimens, accounting for 7.0% of the total specimens, and the nucleotide sequences of the G genes of 84 HMPV strains were determined. 28352258 6 52 theme specimens 1267:1275 arg1 % 1252:1252 7.0% 1249:1252 7.0% of the total specimens 1249:1275 HMPV was detected in 91 specimens, accounting for 7.0% of the total specimens, and the nucleotide sequences of the G genes of 84 HMPV strains were determined. 28352258 8 53 contain had 1544:1546 arg2 180nt-dup 1578:1586 180nt-dup 1578:1586 180nt-dup 1578:1586 Approximately half the HMPV A2b subgroup strains detected since 2014 had a 180-nucleotide duplication (180nt-dup) in the G gene and clustered on a phylogenic tree with four classical 180nt-dup-lacking HMPV A2b strains prevalent between 2014 and 2015. 28352258 8 53 contain had 1544:1546 arg2 duplication 1565:1575 a 180-nucleotide duplication 1548:1575 a 180-nucleotide duplication (180nt-dup) in the G gene 1548:1601 Approximately half the HMPV A2b subgroup strains detected since 2014 had a 180-nucleotide duplication (180nt-dup) in the G gene and clustered on a phylogenic tree with four classical 180nt-dup-lacking HMPV A2b strains prevalent between 2014 and 2015. 28352258 8 53 contain had 1544:1546 arg1 half 1489:1492 half 1489:1492 half the HMPV A2b subgroup strains detected since 2014 1489:1542 Approximately half the HMPV A2b subgroup strains detected since 2014 had a 180-nucleotide duplication (180nt-dup) in the G gene and clustered on a phylogenic tree with four classical 180nt-dup-lacking HMPV A2b strains prevalent between 2014 and 2015. 28352258 5 54 theme Japan 944:948 arg1 Surveillance 907:918 the National Epidemiological Surveillance 878:918 the National Epidemiological Surveillance of Infectious Diseases, Japan, 1308 clinical specimens (throat swabs, nasal swabs, nasal secretions, and nasal aspirate fluids) collected at 24 hospitals or clinics in Yokohama City 878:1100 As a part of the National Epidemiological Surveillance of Infectious Diseases, Japan, 1308 clinical specimens (throat swabs, nasal swabs, nasal secretions, and nasal aspirate fluids) collected at 24 hospitals or clinics in Yokohama City were screened for 15 major respiratory viruses with a multiplex reverse transcription-PCR assay. 28352258 3 55 theme drugs 636:640 arg1 insight 558:564 valuable insight 549:564 valuable insight for the control of HMPV 549:588 Molecular epidemiological, genetic, and antigenetic evolutionary studies of HMPV will strengthen our understanding of the epidemic behavior of the virus and provide valuable insight for the control of HMPV and the development of vaccines and antiviral drugs against HMPV infection. 28352258 3 55 theme drugs 636:640 arg1 development 598:608 the development 594:608 the development of vaccines and antiviral drugs against HMPV infection 594:663 Molecular epidemiological, genetic, and antigenetic evolutionary studies of HMPV will strengthen our understanding of the epidemic behavior of the virus and provide valuable insight for the control of HMPV and the development of vaccines and antiviral drugs against HMPV infection. 28352258 4 56 theme G 738:738 arg1 gene 740:743 the G gene 734:743 the G gene 734:743 In this study, the nucleotide sequence of and genetic variations in the G gene were analyzed in HMPV strains prevalent in Yokohama City, in the Kanto area, Japan, between January 2013 and June 2016. 28352258 3 57 theme evolutionary 436:447 arg1 studies 449:455 Molecular epidemiological, genetic, and antigenetic evolutionary studies 384:455 Molecular epidemiological, genetic, and antigenetic evolutionary studies of HMPV 384:463 Molecular epidemiological, genetic, and antigenetic evolutionary studies of HMPV will strengthen our understanding of the epidemic behavior of the virus and provide valuable insight for the control of HMPV and the development of vaccines and antiviral drugs against HMPV infection. 28352258 1 58 theme family 182:187 arg1 Paramyxoviridae 189:203 the family Paramyxoviridae 178:203 the family Paramyxoviridae 178:203 Human metapneumovirus (HMPV), a member of the family Paramyxoviridae, was first isolated in 2001. 28352258 5 59 theme Epidemiological 891:905 arg1 Surveillance 907:918 the National Epidemiological Surveillance 878:918 the National Epidemiological Surveillance of Infectious Diseases, Japan, 1308 clinical specimens (throat swabs, nasal swabs, nasal secretions, and nasal aspirate fluids) collected at 24 hospitals or clinics in Yokohama City 878:1100 As a part of the National Epidemiological Surveillance of Infectious Diseases, Japan, 1308 clinical specimens (throat swabs, nasal swabs, nasal secretions, and nasal aspirate fluids) collected at 24 hospitals or clinics in Yokohama City were screened for 15 major respiratory viruses with a multiplex reverse transcription-PCR assay. 28352258 2 60 theme respiratory 327:337 arg1 infections 339:348 acute respiratory infections 321:348 acute respiratory infections 321:348 Seroepidemiological studies have shown that HMPV has been a major etiological agent of acute respiratory infections in humans for more than 50 years. 28352258 6 61 theme HMPV 1328:1331 arg1 strains 1333:1339 84 HMPV strains 1325:1339 84 HMPV strains 1325:1339 HMPV was detected in 91 specimens, accounting for 7.0% of the total specimens, and the nucleotide sequences of the G genes of 84 HMPV strains were determined. 28352258 9 62 link O-linked 1859:1866 arg1 sugars 1868:1873 O-linked sugars 1859:1873 O-linked sugars 1859:1873 The 180nt-dup causes a 60-amino-acid duplication (60aa-dup) in the G protein, creating 23-25 additional potential acceptor sites for O-linked sugars. 28352258 5 63 theme clinics 1077:1083 arg1 Surveillance 907:918 the National Epidemiological Surveillance 878:918 the National Epidemiological Surveillance of Infectious Diseases, Japan, 1308 clinical specimens (throat swabs, nasal swabs, nasal secretions, and nasal aspirate fluids) collected at 24 hospitals or clinics in Yokohama City 878:1100 As a part of the National Epidemiological Surveillance of Infectious Diseases, Japan, 1308 clinical specimens (throat swabs, nasal swabs, nasal secretions, and nasal aspirate fluids) collected at 24 hospitals or clinics in Yokohama City were screened for 15 major respiratory viruses with a multiplex reverse transcription-PCR assay. 28352258 9 64 theme O-linked 1859:1866 arg1 sugars 1868:1873 O-linked sugars 1859:1873 O-linked sugars 1859:1873 The 180nt-dup causes a 60-amino-acid duplication (60aa-dup) in the G protein, creating 23-25 additional potential acceptor sites for O-linked sugars. 28352258 5 65 dep specimens 965:973 arg1 swabs 983:987 throat swabs 976:987 throat swabs 976:987 As a part of the National Epidemiological Surveillance of Infectious Diseases, Japan, 1308 clinical specimens (throat swabs, nasal swabs, nasal secretions, and nasal aspirate fluids) collected at 24 hospitals or clinics in Yokohama City were screened for 15 major respiratory viruses with a multiplex reverse transcription-PCR assay. 28352258 5 65 dep specimens 965:973 arg1 swabs 996:1000 nasal swabs 990:1000 nasal swabs 990:1000 As a part of the National Epidemiological Surveillance of Infectious Diseases, Japan, 1308 clinical specimens (throat swabs, nasal swabs, nasal secretions, and nasal aspirate fluids) collected at 24 hospitals or clinics in Yokohama City were screened for 15 major respiratory viruses with a multiplex reverse transcription-PCR assay. 28352258 5 65 dep specimens 965:973 arg1 secretions 1009:1018 nasal secretions 1003:1018 nasal secretions 1003:1018 As a part of the National Epidemiological Surveillance of Infectious Diseases, Japan, 1308 clinical specimens (throat swabs, nasal swabs, nasal secretions, and nasal aspirate fluids) collected at 24 hospitals or clinics in Yokohama City were screened for 15 major respiratory viruses with a multiplex reverse transcription-PCR assay. 28352258 5 65 dep specimens 965:973 arg1 fluids 1040:1045 nasal aspirate fluids 1025:1045 nasal aspirate fluids 1025:1045 As a part of the National Epidemiological Surveillance of Infectious Diseases, Japan, 1308 clinical specimens (throat swabs, nasal swabs, nasal secretions, and nasal aspirate fluids) collected at 24 hospitals or clinics in Yokohama City were screened for 15 major respiratory viruses with a multiplex reverse transcription-PCR assay. 28352258 3 66 theme HMPV 650:653 arg1 infection 655:663 HMPV infection 650:663 HMPV infection 650:663 Molecular epidemiological, genetic, and antigenetic evolutionary studies of HMPV will strengthen our understanding of the epidemic behavior of the virus and provide valuable insight for the control of HMPV and the development of vaccines and antiviral drugs against HMPV infection. 28352258 8 67 theme classical 1648:1656 arg1 strains 1685:1691 four classical 180nt-dup-lacking HMPV A2b strains 1643:1691 four classical 180nt-dup-lacking HMPV A2b strains prevalent between 2014 and 2015 1643:1723 Approximately half the HMPV A2b subgroup strains detected since 2014 had a 180-nucleotide duplication (180nt-dup) in the G gene and clustered on a phylogenic tree with four classical 180nt-dup-lacking HMPV A2b strains prevalent between 2014 and 2015. 28352258 3 68 theme epidemic 506:513 arg1 behavior 515:522 the epidemic behavior 502:522 the epidemic behavior of the virus 502:535 Molecular epidemiological, genetic, and antigenetic evolutionary studies of HMPV will strengthen our understanding of the epidemic behavior of the virus and provide valuable insight for the control of HMPV and the development of vaccines and antiviral drugs against HMPV infection. 28352258 6 69 theme G 1314:1314 arg1 genes 1316:1320 the G genes 1310:1320 the G genes of 84 HMPV strains 1310:1339 HMPV was detected in 91 specimens, accounting for 7.0% of the total specimens, and the nucleotide sequences of the G genes of 84 HMPV strains were determined. 28352258 8 70 theme HMPV 1676:1679 arg1 strains 1685:1691 four classical 180nt-dup-lacking HMPV A2b strains 1643:1691 four classical 180nt-dup-lacking HMPV A2b strains prevalent between 2014 and 2015 1643:1723 Approximately half the HMPV A2b subgroup strains detected since 2014 had a 180-nucleotide duplication (180nt-dup) in the G gene and clustered on a phylogenic tree with four classical 180nt-dup-lacking HMPV A2b strains prevalent between 2014 and 2015. 28352258 11 71 dep strains 2100:2106 arg1 gained 2108:2113 gained 2108:2113 strains gained an advantage that allowed their efficient spread in the community 2100:2179 The detailed mechanism by which the A2b180nt-dup HMPV strains gained an advantage that allowed their efficient spread in the community and the effects of 60aa-dup on HMPV virulence must be clarified. 28352258 2 72 theme Seroepidemiological 234:252 arg1 studies 254:260 Seroepidemiological studies 234:260 Seroepidemiological studies 234:260 Seroepidemiological studies have shown that HMPV has been a major etiological agent of acute respiratory infections in humans for more than 50 years. 28352258 4 73 theme prevalent 775:783 arg1 strains 767:773 HMPV strains 762:773 HMPV strains prevalent in Yokohama City 762:800 In this study, the nucleotide sequence of and genetic variations in the G gene were analyzed in HMPV strains prevalent in Yokohama City, in the Kanto area, Japan, between January 2013 and June 2016. 28352258 3 74 theme virus 531:535 arg1 behavior 515:522 the epidemic behavior 502:522 the epidemic behavior of the virus 502:535 Molecular epidemiological, genetic, and antigenetic evolutionary studies of HMPV will strengthen our understanding of the epidemic behavior of the virus and provide valuable insight for the control of HMPV and the development of vaccines and antiviral drugs against HMPV infection. 28352258 8 75 theme A2b 1503:1505 arg1 strains 1516:1522 the HMPV A2b subgroup strains 1494:1522 half the HMPV A2b subgroup strains detected since 2014 1489:1542 Approximately half the HMPV A2b subgroup strains detected since 2014 had a 180-nucleotide duplication (180nt-dup) in the G gene and clustered on a phylogenic tree with four classical 180nt-dup-lacking HMPV A2b strains prevalent between 2014 and 2015. 28352258 11 76 theme detailed 2050:2057 arg1 mechanism 2059:2067 The detailed mechanism 2046:2067 The detailed mechanism by which the A2b180nt-dup HMPV strains gained an advantage that allowed their efficient spread in the community 2046:2179 The detailed mechanism by which the A2b180nt-dup HMPV strains gained an advantage that allowed their efficient spread in the community and the effects of 60aa-dup on HMPV virulence must be clarified. 28352258 2 77 theme major 294:298 arg1 HMPV 278:281 HMPV 278:281 HMPV 278:281 Seroepidemiological studies have shown that HMPV has been a major etiological agent of acute respiratory infections in humans for more than 50 years. 28352258 2 77 theme major 294:298 arg1 agent 312:316 a major etiological agent 292:316 a major etiological agent of acute respiratory infections in humans for more than 50 years 292:381 Seroepidemiological studies have shown that HMPV has been a major etiological agent of acute respiratory infections in humans for more than 50 years. 28352258 5 78 from clinics 1077:1083 arg1 City 1097:1100 City 1097:1100 City 1097:1100 As a part of the National Epidemiological Surveillance of Infectious Diseases, Japan, 1308 clinical specimens (throat swabs, nasal swabs, nasal secretions, and nasal aspirate fluids) collected at 24 hospitals or clinics in Yokohama City were screened for 15 major respiratory viruses with a multiplex reverse transcription-PCR assay. 28352258 5 79 theme throat 976:981 arg1 swabs 983:987 throat swabs 976:987 throat swabs 976:987 As a part of the National Epidemiological Surveillance of Infectious Diseases, Japan, 1308 clinical specimens (throat swabs, nasal swabs, nasal secretions, and nasal aspirate fluids) collected at 24 hospitals or clinics in Yokohama City were screened for 15 major respiratory viruses with a multiplex reverse transcription-PCR assay. 28352258 5 80 from Diseases 934:941 arg1 City 1097:1100 City 1097:1100 City 1097:1100 As a part of the National Epidemiological Surveillance of Infectious Diseases, Japan, 1308 clinical specimens (throat swabs, nasal swabs, nasal secretions, and nasal aspirate fluids) collected at 24 hospitals or clinics in Yokohama City were screened for 15 major respiratory viruses with a multiplex reverse transcription-PCR assay. 28352258 8 81 dep half 1489:1492 arg1 strains 1516:1522 the HMPV A2b subgroup strains 1494:1522 half the HMPV A2b subgroup strains detected since 2014 1489:1542 Approximately half the HMPV A2b subgroup strains detected since 2014 had a 180-nucleotide duplication (180nt-dup) in the G gene and clustered on a phylogenic tree with four classical 180nt-dup-lacking HMPV A2b strains prevalent between 2014 and 2015. 28352258 9 82 theme 60-amino-acid 1749:1761 arg1 60aa-dup 1776:1783 60aa-dup 1776:1783 60aa-dup 1776:1783 The 180nt-dup causes a 60-amino-acid duplication (60aa-dup) in the G protein, creating 23-25 additional potential acceptor sites for O-linked sugars. 28352258 9 82 theme 60-amino-acid 1749:1761 arg1 duplication 1763:1773 a 60-amino-acid duplication 1747:1773 a 60-amino-acid duplication (60aa-dup) in the G protein 1747:1801 The 180nt-dup causes a 60-amino-acid duplication (60aa-dup) in the G protein, creating 23-25 additional potential acceptor sites for O-linked sugars. 28352258 8 83 theme 180-nucleotide 1550:1563 arg1 180nt-dup 1578:1586 180nt-dup 1578:1586 180nt-dup 1578:1586 Approximately half the HMPV A2b subgroup strains detected since 2014 had a 180-nucleotide duplication (180nt-dup) in the G gene and clustered on a phylogenic tree with four classical 180nt-dup-lacking HMPV A2b strains prevalent between 2014 and 2015. 28352258 8 83 theme 180-nucleotide 1550:1563 arg1 duplication 1565:1575 a 180-nucleotide duplication 1548:1575 a 180-nucleotide duplication (180nt-dup) in the G gene 1548:1601 Approximately half the HMPV A2b subgroup strains detected since 2014 had a 180-nucleotide duplication (180nt-dup) in the G gene and clustered on a phylogenic tree with four classical 180nt-dup-lacking HMPV A2b strains prevalent between 2014 and 2015. 28352258 5 84 theme reverse 1166:1172 arg1 assay 1192:1196 a multiplex reverse transcription-PCR assay 1154:1196 a multiplex reverse transcription-PCR assay 1154:1196 As a part of the National Epidemiological Surveillance of Infectious Diseases, Japan, 1308 clinical specimens (throat swabs, nasal swabs, nasal secretions, and nasal aspirate fluids) collected at 24 hospitals or clinics in Yokohama City were screened for 15 major respiratory viruses with a multiplex reverse transcription-PCR assay. 28352258 6 85 theme total 1261:1265 arg1 specimens 1267:1275 the total specimens 1257:1275 the total specimens 1257:1275 HMPV was detected in 91 specimens, accounting for 7.0% of the total specimens, and the nucleotide sequences of the G genes of 84 HMPV strains were determined. 28352258 5 86 theme specimens 965:973 arg1 Surveillance 907:918 the National Epidemiological Surveillance 878:918 the National Epidemiological Surveillance of Infectious Diseases, Japan, 1308 clinical specimens (throat swabs, nasal swabs, nasal secretions, and nasal aspirate fluids) collected at 24 hospitals or clinics in Yokohama City 878:1100 As a part of the National Epidemiological Surveillance of Infectious Diseases, Japan, 1308 clinical specimens (throat swabs, nasal swabs, nasal secretions, and nasal aspirate fluids) collected at 24 hospitals or clinics in Yokohama City were screened for 15 major respiratory viruses with a multiplex reverse transcription-PCR assay. 28352258 4 87 from gene 740:743 arg1 sequence 696:703 the nucleotide sequence 681:703 the nucleotide sequence of and genetic variations in the G gene 681:743 In this study, the nucleotide sequence of and genetic variations in the G gene were analyzed in HMPV strains prevalent in Yokohama City, in the Kanto area, Japan, between January 2013 and June 2016. 28352258 5 88 theme major 1123:1127 arg1 viruses 1141:1147 15 major respiratory viruses 1120:1147 15 major respiratory viruses with a multiplex reverse transcription-PCR assay 1120:1196 As a part of the National Epidemiological Surveillance of Infectious Diseases, Japan, 1308 clinical specimens (throat swabs, nasal swabs, nasal secretions, and nasal aspirate fluids) collected at 24 hospitals or clinics in Yokohama City were screened for 15 major respiratory viruses with a multiplex reverse transcription-PCR assay. 28352258 0 89 theme Strains 79:85 arg1 Duplication 15:25 180-Nucleotide Duplication 0:25 180-Nucleotide Duplication in the G Gene of Human metapneumovirus A2b Subgroup Strains 0:85 180-Nucleotide Duplication in the G Gene of Human metapneumovirus A2b Subgroup Strains Circulating in Yokohama City, Japan, since 2014. 28352258 1 90 theme Human 136:140 arg1 member 168:173 a member 166:173 a member of the family Paramyxoviridae 166:203 Human metapneumovirus (HMPV), a member of the family Paramyxoviridae, was first isolated in 2001. 28352258 1 90 theme Human 136:140 arg1 HMPV 159:162 HMPV 159:162 HMPV 159:162 Human metapneumovirus (HMPV), a member of the family Paramyxoviridae, was first isolated in 2001. 28352258 1 90 theme Human 136:140 arg1 metapneumovirus 142:156 Human metapneumovirus 136:156 Human metapneumovirus (HMPV) 136:163 Human metapneumovirus (HMPV), a member of the family Paramyxoviridae, was first isolated in 2001. 28352258 4 91 from City 797:800 arg1 prevalent 775:783 prevalent 775:783 prevalent 775:783 In this study, the nucleotide sequence of and genetic variations in the G gene were analyzed in HMPV strains prevalent in Yokohama City, in the Kanto area, Japan, between January 2013 and June 2016. 28352258 8 92 theme prevalent 1693:1701 arg1 strains 1685:1691 four classical 180nt-dup-lacking HMPV A2b strains 1643:1691 four classical 180nt-dup-lacking HMPV A2b strains prevalent between 2014 and 2015 1643:1723 Approximately half the HMPV A2b subgroup strains detected since 2014 had a 180-nucleotide duplication (180nt-dup) in the G gene and clustered on a phylogenic tree with four classical 180nt-dup-lacking HMPV A2b strains prevalent between 2014 and 2015. 28352258 0 93 from Duplication 15:25 arg1 Gene 36:39 the G Gene 30:39 the G Gene 30:39 180-Nucleotide Duplication in the G Gene of Human metapneumovirus A2b Subgroup Strains Circulating in Yokohama City, Japan, since 2014. 28352258 11 94 theme efficient 2147:2155 arg1 spread 2157:2162 their efficient spread 2141:2162 their efficient spread in the community 2141:2179 The detailed mechanism by which the A2b180nt-dup HMPV strains gained an advantage that allowed their efficient spread in the community and the effects of 60aa-dup on HMPV virulence must be clarified. 28352258 5 95 theme nasal 1025:1029 arg1 fluids 1040:1045 nasal aspirate fluids 1025:1045 nasal aspirate fluids 1025:1045 As a part of the National Epidemiological Surveillance of Infectious Diseases, Japan, 1308 clinical specimens (throat swabs, nasal swabs, nasal secretions, and nasal aspirate fluids) collected at 24 hospitals or clinics in Yokohama City were screened for 15 major respiratory viruses with a multiplex reverse transcription-PCR assay. 28352258 4 96 from variations 720:729 arg1 gene 740:743 the G gene 734:743 the G gene 734:743 In this study, the nucleotide sequence of and genetic variations in the G gene were analyzed in HMPV strains prevalent in Yokohama City, in the Kanto area, Japan, between January 2013 and June 2016. 28352258 4 97 dep January 837:843 arg1 2013 845:848 2013 845:848 January 2013 837:848 In this study, the nucleotide sequence of and genetic variations in the G gene were analyzed in HMPV strains prevalent in Yokohama City, in the Kanto area, Japan, between January 2013 and June 2016. 28352258 4 98 theme variations 720:729 arg1 sequence 696:703 the nucleotide sequence 681:703 the nucleotide sequence of and genetic variations in the G gene 681:743 In this study, the nucleotide sequence of and genetic variations in the G gene were analyzed in HMPV strains prevalent in Yokohama City, in the Kanto area, Japan, between January 2013 and June 2016. 28352258 11 99 from effects 2189:2195 arg1 virulence 2217:2225 HMPV virulence 2212:2225 HMPV virulence 2212:2225 The detailed mechanism by which the A2b180nt-dup HMPV strains gained an advantage that allowed their efficient spread in the community and the effects of 60aa-dup on HMPV virulence must be clarified. 28352258 4 100 from prevalent 775:783 arg1 City 797:800 City 797:800 City 797:800 In this study, the nucleotide sequence of and genetic variations in the G gene were analyzed in HMPV strains prevalent in Yokohama City, in the Kanto area, Japan, between January 2013 and June 2016. 28352258 4 101 from sequence 696:703 arg1 gene 740:743 the G gene 734:743 the G gene 734:743 In this study, the nucleotide sequence of and genetic variations in the G gene were analyzed in HMPV strains prevalent in Yokohama City, in the Kanto area, Japan, between January 2013 and June 2016. 28352258 9 102 theme additional 1819:1828 arg1 sites 1849:1853 23-25 additional potential acceptor sites 1813:1853 23-25 additional potential acceptor sites for O-linked sugars 1813:1873 The 180nt-dup causes a 60-amino-acid duplication (60aa-dup) in the G protein, creating 23-25 additional potential acceptor sites for O-linked sugars. 28352258 2 103 theme infections 339:348 arg1 HMPV 278:281 HMPV 278:281 HMPV 278:281 Seroepidemiological studies have shown that HMPV has been a major etiological agent of acute respiratory infections in humans for more than 50 years. 28352258 2 103 theme infections 339:348 arg1 agent 312:316 a major etiological agent 292:316 a major etiological agent of acute respiratory infections in humans for more than 50 years 292:381 Seroepidemiological studies have shown that HMPV has been a major etiological agent of acute respiratory infections in humans for more than 50 years. 28352258 9 104 theme acceptor 1840:1847 arg1 sites 1849:1853 23-25 additional potential acceptor sites 1813:1853 23-25 additional potential acceptor sites for O-linked sugars 1813:1873 The 180nt-dup causes a 60-amino-acid duplication (60aa-dup) in the G protein, creating 23-25 additional potential acceptor sites for O-linked sugars. 28352258 3 105 theme antigenetic 424:434 arg1 studies 449:455 Molecular epidemiological, genetic, and antigenetic evolutionary studies 384:455 Molecular epidemiological, genetic, and antigenetic evolutionary studies of HMPV 384:463 Molecular epidemiological, genetic, and antigenetic evolutionary studies of HMPV will strengthen our understanding of the epidemic behavior of the virus and provide valuable insight for the control of HMPV and the development of vaccines and antiviral drugs against HMPV infection. 28352258 5 106 theme Infectious 923:932 arg1 Diseases 934:941 Infectious Diseases 923:941 Infectious Diseases 923:941 As a part of the National Epidemiological Surveillance of Infectious Diseases, Japan, 1308 clinical specimens (throat swabs, nasal swabs, nasal secretions, and nasal aspirate fluids) collected at 24 hospitals or clinics in Yokohama City were screened for 15 major respiratory viruses with a multiplex reverse transcription-PCR assay. 28352258 0 107 theme Human 44:48 arg1 Strains 79:85 Human metapneumovirus A2b Subgroup Strains 44:85 Human metapneumovirus A2b Subgroup Strains 44:85 180-Nucleotide Duplication in the G Gene of Human metapneumovirus A2b Subgroup Strains Circulating in Yokohama City, Japan, since 2014. 28352258 3 108 theme antiviral 626:634 arg1 drugs 636:640 antiviral drugs 626:640 antiviral drugs 626:640 Molecular epidemiological, genetic, and antigenetic evolutionary studies of HMPV will strengthen our understanding of the epidemic behavior of the virus and provide valuable insight for the control of HMPV and the development of vaccines and antiviral drugs against HMPV infection. 28352258 4 109 theme HMPV 762:765 arg1 strains 767:773 HMPV strains 762:773 HMPV strains prevalent in Yokohama City 762:800 In this study, the nucleotide sequence of and genetic variations in the G gene were analyzed in HMPV strains prevalent in Yokohama City, in the Kanto area, Japan, between January 2013 and June 2016. 28352258 3 110 theme HMPV 460:463 arg1 studies 449:455 Molecular epidemiological, genetic, and antigenetic evolutionary studies 384:455 Molecular epidemiological, genetic, and antigenetic evolutionary studies of HMPV 384:463 Molecular epidemiological, genetic, and antigenetic evolutionary studies of HMPV will strengthen our understanding of the epidemic behavior of the virus and provide valuable insight for the control of HMPV and the development of vaccines and antiviral drugs against HMPV infection. 28352258 5 111 theme National 882:889 arg1 Surveillance 907:918 the National Epidemiological Surveillance 878:918 the National Epidemiological Surveillance of Infectious Diseases, Japan, 1308 clinical specimens (throat swabs, nasal swabs, nasal secretions, and nasal aspirate fluids) collected at 24 hospitals or clinics in Yokohama City 878:1100 As a part of the National Epidemiological Surveillance of Infectious Diseases, Japan, 1308 clinical specimens (throat swabs, nasal swabs, nasal secretions, and nasal aspirate fluids) collected at 24 hospitals or clinics in Yokohama City were screened for 15 major respiratory viruses with a multiplex reverse transcription-PCR assay. 28352258 3 112 theme vaccines 613:620 arg1 insight 558:564 valuable insight 549:564 valuable insight for the control of HMPV 549:588 Molecular epidemiological, genetic, and antigenetic evolutionary studies of HMPV will strengthen our understanding of the epidemic behavior of the virus and provide valuable insight for the control of HMPV and the development of vaccines and antiviral drugs against HMPV infection. 28352258 3 112 theme vaccines 613:620 arg1 development 598:608 the development 594:608 the development of vaccines and antiviral drugs against HMPV infection 594:663 Molecular epidemiological, genetic, and antigenetic evolutionary studies of HMPV will strengthen our understanding of the epidemic behavior of the virus and provide valuable insight for the control of HMPV and the development of vaccines and antiviral drugs against HMPV infection. 28352258 10 113 theme A2b 1953:1955 arg1 strains 1957:1963 HMPV A2b strains 1948:1963 HMPV A2b strains with 180nt-dup (A2b180nt-dup HMPV) 1948:1998 Our data suggest that 180nt-dup occurred between 2011 and 2013 and that HMPV A2b strains with 180nt-dup (A2b180nt-dup HMPV) became major epidemic strains within 3 years. 28352258 6 114 theme strains 1333:1339 arg1 genes 1316:1320 the G genes 1310:1320 the G genes of 84 HMPV strains 1310:1339 HMPV was detected in 91 specimens, accounting for 7.0% of the total specimens, and the nucleotide sequences of the G genes of 84 HMPV strains were determined. 28352258 1 115 theme Paramyxoviridae 189:203 arg1 member 168:173 a member 166:173 a member of the family Paramyxoviridae 166:203 Human metapneumovirus (HMPV), a member of the family Paramyxoviridae, was first isolated in 2001. 28352258 1 115 theme Paramyxoviridae 189:203 arg1 metapneumovirus 142:156 Human metapneumovirus 136:156 Human metapneumovirus (HMPV) 136:163 Human metapneumovirus (HMPV), a member of the family Paramyxoviridae, was first isolated in 2001. 28352258 5 116 theme Surveillance 907:918 arg1 part 870:873 a part 868:873 a part of the National Epidemiological Surveillance of Infectious Diseases, Japan, 1308 clinical specimens (throat swabs, nasal swabs, nasal secretions, and nasal aspirate fluids) collected at 24 hospitals or clinics in Yokohama City 868:1100 As a part of the National Epidemiological Surveillance of Infectious Diseases, Japan, 1308 clinical specimens (throat swabs, nasal swabs, nasal secretions, and nasal aspirate fluids) collected at 24 hospitals or clinics in Yokohama City were screened for 15 major respiratory viruses with a multiplex reverse transcription-PCR assay. 28352258 11 117 theme A2b180nt-dup 2082:2093 arg1 HMPV 2095:2098 the A2b180nt-dup HMPV 2078:2098 the A2b180nt-dup HMPV 2078:2098 The detailed mechanism by which the A2b180nt-dup HMPV strains gained an advantage that allowed their efficient spread in the community and the effects of 60aa-dup on HMPV virulence must be clarified. 28352258 0 118 from Japan 117:121 arg1 Circulating 87:97 Circulating 87:97 Circulating 87:97 180-Nucleotide Duplication in the G Gene of Human metapneumovirus A2b Subgroup Strains Circulating in Yokohama City, Japan, since 2014. 28352258 2 119 theme acute 321:325 arg1 infections 339:348 acute respiratory infections 321:348 acute respiratory infections 321:348 Seroepidemiological studies have shown that HMPV has been a major etiological agent of acute respiratory infections in humans for more than 50 years. 27687229 7 0 theme Y. 1202:1203 arg1 CTD 1234:1236 CTD 1234:1236 CTD 1234:1236 lipolytica OGT, carrying the human tetratricopeptide repeat (TPR) domain along with the Y. lipolytica catalytic domain (CTD), mediated the transfer of O-GlcNAc moiety during the in vitro assays. 27687229 7 0 theme Y. 1202:1203 arg1 domain 1226:1231 the Y. lipolytica catalytic domain 1198:1231 the human tetratricopeptide repeat (TPR) domain along with the Y. lipolytica catalytic domain (CTD) 1139:1237 lipolytica OGT, carrying the human tetratricopeptide repeat (TPR) domain along with the Y. lipolytica catalytic domain (CTD), mediated the transfer of O-GlcNAc moiety during the in vitro assays. 27687229 8 1 theme fragment 1464:1471 arg1 overexpression 1433:1446 overexpression 1433:1446 overexpression of only the CTD fragment 1433:1471 Although the overexpression of full-length OGTs inhibited the growth of S. cerevisiae, no such inhibition was obtained upon overexpression of only the CTD fragment, indicating the role of TPR domain in growth inhibition. 27687229 4 2 theme S. 886:887 arg1 host 881:884 the heterologous host 864:884 the heterologous host S. cerevisiae 864:898 Immunoblotting assays using antibody against O-GlcNAc revealed that recombinant hOGT (rhOGT), but not the recombinant YlOGT (rYlOGT), undergoes auto-O-GlcNAcylation in the heterologous host S. cerevisiae. 27687229 1 3 from modification 217:228 arg1 processes 247:255 many cellular processes 233:255 many cellular processes 233:255 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation is an important post-translational modification in many cellular processes. 27687229 6 4 theme chimeric 1096:1103 arg1 human-Y 1105:1111 the chimeric human-Y 1092:1111 the chimeric human-Y 1092:1111 However, the chimeric human-Y. 27687229 1 5 theme important 188:196 arg1 modification 217:228 an important post-translational modification 185:228 an important post-translational modification in many cellular processes 185:255 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation is an important post-translational modification in many cellular processes. 27687229 1 5 theme important 188:196 arg1 glycosylation 168:180 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation 126:180 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation 126:180 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation is an important post-translational modification in many cellular processes. 27687229 9 6 theme OGT 1596:1598 arg1 analysis 1573:1580 the functional analysis 1558:1580 the functional analysis of the fungal OGT 1558:1598 This is the first report on the functional analysis of the fungal OGT, indicating that the Y. lipolytica OGT retains its catalytic activity, although the physiological role and substrates of YlOGT remain to be elucidated. 27687229 9 7 theme YlOGT 1721:1725 arg1 substrates 1707:1716 substrates 1707:1716 substrates of YlOGT 1707:1725 This is the first report on the functional analysis of the fungal OGT, indicating that the Y. lipolytica OGT retains its catalytic activity, although the physiological role and substrates of YlOGT remain to be elucidated. 27687229 9 7 theme YlOGT 1721:1725 arg1 role 1698:1701 the physiological role 1680:1701 the physiological role 1680:1701 This is the first report on the functional analysis of the fungal OGT, indicating that the Y. lipolytica OGT retains its catalytic activity, although the physiological role and substrates of YlOGT remain to be elucidated. 27687229 8 8 theme growth 1511:1516 arg1 inhibition 1518:1527 growth inhibition 1511:1527 growth inhibition 1511:1527 Although the overexpression of full-length OGTs inhibited the growth of S. cerevisiae, no such inhibition was obtained upon overexpression of only the CTD fragment, indicating the role of TPR domain in growth inhibition. 27687229 7 9 contain carrying 1130:1137 arg2 domain 1226:1231 the Y. lipolytica catalytic domain 1198:1231 the human tetratricopeptide repeat (TPR) domain along with the Y. lipolytica catalytic domain (CTD) 1139:1237 lipolytica OGT, carrying the human tetratricopeptide repeat (TPR) domain along with the Y. lipolytica catalytic domain (CTD), mediated the transfer of O-GlcNAc moiety during the in vitro assays. 27687229 7 9 contain carrying 1130:1137 arg2 domain 1180:1185 the human tetratricopeptide repeat (TPR) domain 1139:1185 the human tetratricopeptide repeat (TPR) domain along with the Y. lipolytica catalytic domain (CTD) 1139:1237 lipolytica OGT, carrying the human tetratricopeptide repeat (TPR) domain along with the Y. lipolytica catalytic domain (CTD), mediated the transfer of O-GlcNAc moiety during the in vitro assays. 27687229 7 9 contain carrying 1130:1137 arg1 OGT 1125:1127 lipolytica OGT 1114:1127 lipolytica OGT 1114:1127 lipolytica OGT, carrying the human tetratricopeptide repeat (TPR) domain along with the Y. lipolytica catalytic domain (CTD), mediated the transfer of O-GlcNAc moiety during the in vitro assays. 27687229 7 9 contain carrying 1130:1137 arg2 CTD 1234:1236 CTD 1234:1236 CTD 1234:1236 lipolytica OGT, carrying the human tetratricopeptide repeat (TPR) domain along with the Y. lipolytica catalytic domain (CTD), mediated the transfer of O-GlcNAc moiety during the in vitro assays. 27687229 9 10 theme first 1542:1546 arg1 report 1548:1553 the first report 1538:1553 the first report on the functional analysis of the fungal OGT 1538:1598 This is the first report on the functional analysis of the fungal OGT, indicating that the Y. lipolytica OGT retains its catalytic activity, although the physiological role and substrates of YlOGT remain to be elucidated. 27687229 9 10 theme first 1542:1546 arg1 This 1530:1533 This 1530:1533 This 1530:1533 This is the first report on the functional analysis of the fungal OGT, indicating that the Y. lipolytica OGT retains its catalytic activity, although the physiological role and substrates of YlOGT remain to be elucidated. 27687229 0 11 theme Saccharomyces 100:112 arg1 cerevisiae 114:123 Saccharomyces cerevisiae 100:123 Saccharomyces cerevisiae 100:123 Functional analysis of recombinant human and Yarrowia lipolytica O-GlcNAc transferases expressed in Saccharomyces cerevisiae. 27687229 7 12 theme lipolytica 1114:1123 arg1 OGT 1125:1127 lipolytica OGT 1114:1127 lipolytica OGT 1114:1127 lipolytica OGT, carrying the human tetratricopeptide repeat (TPR) domain along with the Y. lipolytica catalytic domain (CTD), mediated the transfer of O-GlcNAc moiety during the in vitro assays. 27687229 5 13 theme in 983:984 arg1 assays 992:997 in vitro assays 983:997 in vitro assays using casein kinase II substrates 983:1031 Moreover, the rhOGT expressed in S. cerevisiae showed a catalytic activity during in vitro assays using casein kinase II substrates, whereas no such activity was obtained in rYlOGT. 27687229 5 14 dep in 983:984 arg1 vitro 986:990 vitro 986:990 vitro 986:990 Moreover, the rhOGT expressed in S. cerevisiae showed a catalytic activity during in vitro assays using casein kinase II substrates, whereas no such activity was obtained in rYlOGT. 27687229 3 15 from proteins 609:616 arg1 cerevisiae 635:644 Saccharomyces cerevisiae 621:644 Saccharomyces cerevisiae 621:644 In this study, we expressed a putative Yarrowia lipolytica OGT (YlOGT), the only homolog identified in the subphylum Saccharomycotina through bioinformatics analysis, and the human OGT (hOGT) as recombinant proteins in Saccharomyces cerevisiae, and performed their functional characterization. 27687229 1 16 theme post-translational 198:215 arg1 modification 217:228 an important post-translational modification 185:228 an important post-translational modification in many cellular processes 185:255 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation is an important post-translational modification in many cellular processes. 27687229 1 16 theme post-translational 198:215 arg1 glycosylation 168:180 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation 126:180 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation 126:180 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation is an important post-translational modification in many cellular processes. 27687229 8 17 theme domain 1501:1506 arg1 role 1489:1492 the role 1485:1492 the role of TPR domain in growth inhibition 1485:1527 Although the overexpression of full-length OGTs inhibited the growth of S. cerevisiae, no such inhibition was obtained upon overexpression of only the CTD fragment, indicating the role of TPR domain in growth inhibition. 27687229 9 18 theme Y. 1621:1622 arg1 OGT 1635:1637 the Y. lipolytica OGT 1617:1637 the Y. lipolytica OGT 1617:1637 This is the first report on the functional analysis of the fungal OGT, indicating that the Y. lipolytica OGT retains its catalytic activity, although the physiological role and substrates of YlOGT remain to be elucidated. 27687229 3 19 theme bioinformatics 544:557 arg1 analysis 559:566 bioinformatics analysis 544:566 bioinformatics analysis 544:566 In this study, we expressed a putative Yarrowia lipolytica OGT (YlOGT), the only homolog identified in the subphylum Saccharomycotina through bioinformatics analysis, and the human OGT (hOGT) as recombinant proteins in Saccharomyces cerevisiae, and performed their functional characterization. 27687229 7 20 theme TPR 1175:1177 arg1 domain 1180:1185 the human tetratricopeptide repeat (TPR) domain 1139:1185 the human tetratricopeptide repeat (TPR) domain along with the Y. lipolytica catalytic domain (CTD) 1139:1237 lipolytica OGT, carrying the human tetratricopeptide repeat (TPR) domain along with the Y. lipolytica catalytic domain (CTD), mediated the transfer of O-GlcNAc moiety during the in vitro assays. 27687229 8 21 theme TPR 1497:1499 arg1 domain 1501:1506 TPR domain 1497:1506 TPR domain 1497:1506 Although the overexpression of full-length OGTs inhibited the growth of S. cerevisiae, no such inhibition was obtained upon overexpression of only the CTD fragment, indicating the role of TPR domain in growth inhibition. 27687229 4 22 theme heterologous 868:879 arg1 host 881:884 the heterologous host 864:884 the heterologous host S. cerevisiae 864:898 Immunoblotting assays using antibody against O-GlcNAc revealed that recombinant hOGT (rhOGT), but not the recombinant YlOGT (rYlOGT), undergoes auto-O-GlcNAcylation in the heterologous host S. cerevisiae. 27687229 5 23 theme kinase 1012:1017 arg1 substrates 1022:1031 casein kinase II substrates 1005:1031 casein kinase II substrates 1005:1031 Moreover, the rhOGT expressed in S. cerevisiae showed a catalytic activity during in vitro assays using casein kinase II substrates, whereas no such activity was obtained in rYlOGT. 27687229 3 24 theme human 577:581 arg1 homolog 483:489 the only homolog 474:489 the only homolog identified in the subphylum Saccharomycotina through bioinformatics analysis 474:566 In this study, we expressed a putative Yarrowia lipolytica OGT (YlOGT), the only homolog identified in the subphylum Saccharomycotina through bioinformatics analysis, and the human OGT (hOGT) as recombinant proteins in Saccharomyces cerevisiae, and performed their functional characterization. 27687229 3 24 theme human 577:581 arg1 proteins 609:616 recombinant proteins 597:616 recombinant proteins in Saccharomyces cerevisiae 597:644 In this study, we expressed a putative Yarrowia lipolytica OGT (YlOGT), the only homolog identified in the subphylum Saccharomycotina through bioinformatics analysis, and the human OGT (hOGT) as recombinant proteins in Saccharomyces cerevisiae, and performed their functional characterization. 27687229 3 24 theme human 577:581 arg1 OGT 461:463 a putative Yarrowia lipolytica OGT 430:463 a putative Yarrowia lipolytica OGT (YlOGT) 430:471 In this study, we expressed a putative Yarrowia lipolytica OGT (YlOGT), the only homolog identified in the subphylum Saccharomycotina through bioinformatics analysis, and the human OGT (hOGT) as recombinant proteins in Saccharomyces cerevisiae, and performed their functional characterization. 27687229 3 24 theme human 577:581 arg1 hOGT 588:591 hOGT 588:591 hOGT 588:591 In this study, we expressed a putative Yarrowia lipolytica OGT (YlOGT), the only homolog identified in the subphylum Saccharomycotina through bioinformatics analysis, and the human OGT (hOGT) as recombinant proteins in Saccharomyces cerevisiae, and performed their functional characterization. 27687229 3 24 theme human 577:581 arg1 OGT 583:585 the human OGT 573:585 the human OGT (hOGT) 573:592 In this study, we expressed a putative Yarrowia lipolytica OGT (YlOGT), the only homolog identified in the subphylum Saccharomycotina through bioinformatics analysis, and the human OGT (hOGT) as recombinant proteins in Saccharomyces cerevisiae, and performed their functional characterization. 27687229 3 25 theme putative 432:439 arg1 homolog 483:489 the only homolog 474:489 the only homolog identified in the subphylum Saccharomycotina through bioinformatics analysis 474:566 In this study, we expressed a putative Yarrowia lipolytica OGT (YlOGT), the only homolog identified in the subphylum Saccharomycotina through bioinformatics analysis, and the human OGT (hOGT) as recombinant proteins in Saccharomyces cerevisiae, and performed their functional characterization. 27687229 3 25 theme putative 432:439 arg1 proteins 609:616 recombinant proteins 597:616 recombinant proteins in Saccharomyces cerevisiae 597:644 In this study, we expressed a putative Yarrowia lipolytica OGT (YlOGT), the only homolog identified in the subphylum Saccharomycotina through bioinformatics analysis, and the human OGT (hOGT) as recombinant proteins in Saccharomyces cerevisiae, and performed their functional characterization. 27687229 3 25 theme putative 432:439 arg1 OGT 461:463 a putative Yarrowia lipolytica OGT 430:463 a putative Yarrowia lipolytica OGT (YlOGT) 430:471 In this study, we expressed a putative Yarrowia lipolytica OGT (YlOGT), the only homolog identified in the subphylum Saccharomycotina through bioinformatics analysis, and the human OGT (hOGT) as recombinant proteins in Saccharomyces cerevisiae, and performed their functional characterization. 27687229 3 25 theme putative 432:439 arg1 OGT 583:585 the human OGT 573:585 the human OGT (hOGT) 573:592 In this study, we expressed a putative Yarrowia lipolytica OGT (YlOGT), the only homolog identified in the subphylum Saccharomycotina through bioinformatics analysis, and the human OGT (hOGT) as recombinant proteins in Saccharomyces cerevisiae, and performed their functional characterization. 27687229 3 25 theme putative 432:439 arg1 YlOGT 466:470 YlOGT 466:470 YlOGT 466:470 In this study, we expressed a putative Yarrowia lipolytica OGT (YlOGT), the only homolog identified in the subphylum Saccharomycotina through bioinformatics analysis, and the human OGT (hOGT) as recombinant proteins in Saccharomyces cerevisiae, and performed their functional characterization. 27687229 0 26 theme Functional 0:9 arg1 analysis 11:18 Functional analysis 0:18 Functional analysis of recombinant human and Yarrowia lipolytica O-GlcNAc transferases 0:85 Functional analysis of recombinant human and Yarrowia lipolytica O-GlcNAc transferases expressed in Saccharomyces cerevisiae. 27687229 7 27 theme tetratricopeptide 1149:1165 arg1 domain 1180:1185 the human tetratricopeptide repeat (TPR) domain 1139:1185 the human tetratricopeptide repeat (TPR) domain along with the Y. lipolytica catalytic domain (CTD) 1139:1237 lipolytica OGT, carrying the human tetratricopeptide repeat (TPR) domain along with the Y. lipolytica catalytic domain (CTD), mediated the transfer of O-GlcNAc moiety during the in vitro assays. 27687229 2 28 theme O-GlcNAc 337:344 arg1 addition 325:332 the addition 321:332 the addition of O-GlcNAc to serine or threonine residues of the target proteins 321:399 It is mediated by O-GlcNAc transferases (OGTs), which catalyze the addition of O-GlcNAc to serine or threonine residues of the target proteins. 27687229 1 29 theme many 233:236 arg1 processes 247:255 many cellular processes 233:255 many cellular processes 233:255 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation is an important post-translational modification in many cellular processes. 27687229 7 30 theme repeat 1167:1172 arg1 domain 1180:1185 the human tetratricopeptide repeat (TPR) domain 1139:1185 the human tetratricopeptide repeat (TPR) domain along with the Y. lipolytica catalytic domain (CTD) 1139:1237 lipolytica OGT, carrying the human tetratricopeptide repeat (TPR) domain along with the Y. lipolytica catalytic domain (CTD), mediated the transfer of O-GlcNAc moiety during the in vitro assays. 27687229 4 31 theme recombinant 764:774 arg1 rhOGT 782:786 rhOGT 782:786 rhOGT 782:786 Immunoblotting assays using antibody against O-GlcNAc revealed that recombinant hOGT (rhOGT), but not the recombinant YlOGT (rYlOGT), undergoes auto-O-GlcNAcylation in the heterologous host S. cerevisiae. 27687229 4 31 theme recombinant 764:774 arg1 hOGT 776:779 recombinant hOGT 764:779 recombinant hOGT (rhOGT) 764:787 Immunoblotting assays using antibody against O-GlcNAc revealed that recombinant hOGT (rhOGT), but not the recombinant YlOGT (rYlOGT), undergoes auto-O-GlcNAcylation in the heterologous host S. cerevisiae. 27687229 9 32 theme functional 1562:1571 arg1 analysis 1573:1580 the functional analysis 1558:1580 the functional analysis of the fungal OGT 1558:1598 This is the first report on the functional analysis of the fungal OGT, indicating that the Y. lipolytica OGT retains its catalytic activity, although the physiological role and substrates of YlOGT remain to be elucidated. 27687229 5 33 theme catalytic 957:965 arg1 activity 967:974 a catalytic activity 955:974 a catalytic activity 955:974 Moreover, the rhOGT expressed in S. cerevisiae showed a catalytic activity during in vitro assays using casein kinase II substrates, whereas no such activity was obtained in rYlOGT. 27687229 7 34 dep in 1292:1293 arg1 vitro 1295:1299 vitro 1295:1299 vitro 1295:1299 lipolytica OGT, carrying the human tetratricopeptide repeat (TPR) domain along with the Y. lipolytica catalytic domain (CTD), mediated the transfer of O-GlcNAc moiety during the in vitro assays. 27687229 1 35 theme cellular 238:245 arg1 processes 247:255 many cellular processes 233:255 many cellular processes 233:255 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation is an important post-translational modification in many cellular processes. 27687229 2 36 dep serine 349:354 arg1 residues 369:376 residues 369:376 residues 369:376 It is mediated by O-GlcNAc transferases (OGTs), which catalyze the addition of O-GlcNAc to serine or threonine residues of the target proteins. 27687229 1 37 theme O-linked 126:133 arg1 modification 217:228 an important post-translational modification 185:228 an important post-translational modification in many cellular processes 185:255 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation is an important post-translational modification in many cellular processes. 27687229 1 37 theme O-linked 126:133 arg1 glycosylation 168:180 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation 126:180 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation 126:180 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation is an important post-translational modification in many cellular processes. 27687229 9 38 from report 1548:1553 arg1 analysis 1573:1580 the functional analysis 1558:1580 the functional analysis of the fungal OGT 1558:1598 This is the first report on the functional analysis of the fungal OGT, indicating that the Y. lipolytica OGT retains its catalytic activity, although the physiological role and substrates of YlOGT remain to be elucidated. 27687229 7 39 theme human 1143:1147 arg1 domain 1180:1185 the human tetratricopeptide repeat (TPR) domain 1139:1185 the human tetratricopeptide repeat (TPR) domain along with the Y. lipolytica catalytic domain (CTD) 1139:1237 lipolytica OGT, carrying the human tetratricopeptide repeat (TPR) domain along with the Y. lipolytica catalytic domain (CTD), mediated the transfer of O-GlcNAc moiety during the in vitro assays. 27687229 9 40 theme catalytic 1651:1659 arg1 activity 1661:1668 its catalytic activity 1647:1668 its catalytic activity 1647:1668 This is the first report on the functional analysis of the fungal OGT, indicating that the Y. lipolytica OGT retains its catalytic activity, although the physiological role and substrates of YlOGT remain to be elucidated. 27687229 2 41 theme O-GlcNAc 276:283 arg1 OGTs 299:302 OGTs 299:302 OGTs 299:302 It is mediated by O-GlcNAc transferases (OGTs), which catalyze the addition of O-GlcNAc to serine or threonine residues of the target proteins. 27687229 2 41 theme O-GlcNAc 276:283 arg1 transferases 285:296 O-GlcNAc transferases 276:296 O-GlcNAc transferases (OGTs) 276:303 It is mediated by O-GlcNAc transferases (OGTs), which catalyze the addition of O-GlcNAc to serine or threonine residues of the target proteins. 27687229 3 42 theme Yarrowia 441:448 arg1 homolog 483:489 the only homolog 474:489 the only homolog identified in the subphylum Saccharomycotina through bioinformatics analysis 474:566 In this study, we expressed a putative Yarrowia lipolytica OGT (YlOGT), the only homolog identified in the subphylum Saccharomycotina through bioinformatics analysis, and the human OGT (hOGT) as recombinant proteins in Saccharomyces cerevisiae, and performed their functional characterization. 27687229 3 42 theme Yarrowia 441:448 arg1 proteins 609:616 recombinant proteins 597:616 recombinant proteins in Saccharomyces cerevisiae 597:644 In this study, we expressed a putative Yarrowia lipolytica OGT (YlOGT), the only homolog identified in the subphylum Saccharomycotina through bioinformatics analysis, and the human OGT (hOGT) as recombinant proteins in Saccharomyces cerevisiae, and performed their functional characterization. 27687229 3 42 theme Yarrowia 441:448 arg1 OGT 461:463 a putative Yarrowia lipolytica OGT 430:463 a putative Yarrowia lipolytica OGT (YlOGT) 430:471 In this study, we expressed a putative Yarrowia lipolytica OGT (YlOGT), the only homolog identified in the subphylum Saccharomycotina through bioinformatics analysis, and the human OGT (hOGT) as recombinant proteins in Saccharomyces cerevisiae, and performed their functional characterization. 27687229 3 42 theme Yarrowia 441:448 arg1 OGT 583:585 the human OGT 573:585 the human OGT (hOGT) 573:592 In this study, we expressed a putative Yarrowia lipolytica OGT (YlOGT), the only homolog identified in the subphylum Saccharomycotina through bioinformatics analysis, and the human OGT (hOGT) as recombinant proteins in Saccharomyces cerevisiae, and performed their functional characterization. 27687229 3 42 theme Yarrowia 441:448 arg1 YlOGT 466:470 YlOGT 466:470 YlOGT 466:470 In this study, we expressed a putative Yarrowia lipolytica OGT (YlOGT), the only homolog identified in the subphylum Saccharomycotina through bioinformatics analysis, and the human OGT (hOGT) as recombinant proteins in Saccharomyces cerevisiae, and performed their functional characterization. 27687229 7 43 theme O-GlcNAc 1265:1272 arg1 moiety 1274:1279 O-GlcNAc moiety 1265:1279 O-GlcNAc moiety 1265:1279 lipolytica OGT, carrying the human tetratricopeptide repeat (TPR) domain along with the Y. lipolytica catalytic domain (CTD), mediated the transfer of O-GlcNAc moiety during the in vitro assays. 27687229 3 44 theme lipolytica 450:459 arg1 homolog 483:489 the only homolog 474:489 the only homolog identified in the subphylum Saccharomycotina through bioinformatics analysis 474:566 In this study, we expressed a putative Yarrowia lipolytica OGT (YlOGT), the only homolog identified in the subphylum Saccharomycotina through bioinformatics analysis, and the human OGT (hOGT) as recombinant proteins in Saccharomyces cerevisiae, and performed their functional characterization. 27687229 3 44 theme lipolytica 450:459 arg1 proteins 609:616 recombinant proteins 597:616 recombinant proteins in Saccharomyces cerevisiae 597:644 In this study, we expressed a putative Yarrowia lipolytica OGT (YlOGT), the only homolog identified in the subphylum Saccharomycotina through bioinformatics analysis, and the human OGT (hOGT) as recombinant proteins in Saccharomyces cerevisiae, and performed their functional characterization. 27687229 3 44 theme lipolytica 450:459 arg1 OGT 461:463 a putative Yarrowia lipolytica OGT 430:463 a putative Yarrowia lipolytica OGT (YlOGT) 430:471 In this study, we expressed a putative Yarrowia lipolytica OGT (YlOGT), the only homolog identified in the subphylum Saccharomycotina through bioinformatics analysis, and the human OGT (hOGT) as recombinant proteins in Saccharomyces cerevisiae, and performed their functional characterization. 27687229 3 44 theme lipolytica 450:459 arg1 OGT 583:585 the human OGT 573:585 the human OGT (hOGT) 573:592 In this study, we expressed a putative Yarrowia lipolytica OGT (YlOGT), the only homolog identified in the subphylum Saccharomycotina through bioinformatics analysis, and the human OGT (hOGT) as recombinant proteins in Saccharomyces cerevisiae, and performed their functional characterization. 27687229 3 44 theme lipolytica 450:459 arg1 YlOGT 466:470 YlOGT 466:470 YlOGT 466:470 In this study, we expressed a putative Yarrowia lipolytica OGT (YlOGT), the only homolog identified in the subphylum Saccharomycotina through bioinformatics analysis, and the human OGT (hOGT) as recombinant proteins in Saccharomyces cerevisiae, and performed their functional characterization. 27687229 0 45 theme human 35:39 arg1 analysis 11:18 Functional analysis 0:18 Functional analysis of recombinant human and Yarrowia lipolytica O-GlcNAc transferases 0:85 Functional analysis of recombinant human and Yarrowia lipolytica O-GlcNAc transferases expressed in Saccharomyces cerevisiae. 27687229 7 46 theme moiety 1274:1279 arg1 transfer 1253:1260 the transfer 1249:1260 the transfer of O-GlcNAc moiety 1249:1279 lipolytica OGT, carrying the human tetratricopeptide repeat (TPR) domain along with the Y. lipolytica catalytic domain (CTD), mediated the transfer of O-GlcNAc moiety during the in vitro assays. 27687229 0 47 theme lipolytica 54:63 arg1 analysis 11:18 Functional analysis 0:18 Functional analysis of recombinant human and Yarrowia lipolytica O-GlcNAc transferases 0:85 Functional analysis of recombinant human and Yarrowia lipolytica O-GlcNAc transferases expressed in Saccharomyces cerevisiae. 27687229 8 48 theme OGTs 1352:1355 arg1 overexpression 1322:1335 the overexpression 1318:1335 the overexpression of full-length OGTs 1318:1355 Although the overexpression of full-length OGTs inhibited the growth of S. cerevisiae, no such inhibition was obtained upon overexpression of only the CTD fragment, indicating the role of TPR domain in growth inhibition. 27687229 0 49 theme O-GlcNAc 65:72 arg1 transferases 74:85 O-GlcNAc transferases 65:85 O-GlcNAc transferases 65:85 Functional analysis of recombinant human and Yarrowia lipolytica O-GlcNAc transferases expressed in Saccharomyces cerevisiae. 27687229 8 50 theme cerevisiae 1384:1393 arg1 growth 1371:1376 the growth 1367:1376 the growth of S. cerevisiae 1367:1393 Although the overexpression of full-length OGTs inhibited the growth of S. cerevisiae, no such inhibition was obtained upon overexpression of only the CTD fragment, indicating the role of TPR domain in growth inhibition. 27687229 8 51 theme full-length 1340:1350 arg1 OGTs 1352:1355 full-length OGTs 1340:1355 full-length OGTs 1340:1355 Although the overexpression of full-length OGTs inhibited the growth of S. cerevisiae, no such inhibition was obtained upon overexpression of only the CTD fragment, indicating the role of TPR domain in growth inhibition. 27687229 1 52 theme β-N-acetylglucosamine 135:155 arg1 modification 217:228 an important post-translational modification 185:228 an important post-translational modification in many cellular processes 185:255 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation is an important post-translational modification in many cellular processes. 27687229 1 52 theme β-N-acetylglucosamine 135:155 arg1 glycosylation 168:180 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation 126:180 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation 126:180 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation is an important post-translational modification in many cellular processes. 27687229 8 53 from role 1489:1492 arg1 inhibition 1518:1527 growth inhibition 1511:1527 growth inhibition 1511:1527 Although the overexpression of full-length OGTs inhibited the growth of S. cerevisiae, no such inhibition was obtained upon overexpression of only the CTD fragment, indicating the role of TPR domain in growth inhibition. 27687229 7 54 dep along 1187:1191 arg1 with 1193:1196 with 1193:1196 with 1193:1196 lipolytica OGT, carrying the human tetratricopeptide repeat (TPR) domain along with the Y. lipolytica catalytic domain (CTD), mediated the transfer of O-GlcNAc moiety during the in vitro assays. 27687229 5 55 theme such 1045:1048 arg1 activity 1050:1057 no such activity 1042:1057 no such activity 1042:1057 Moreover, the rhOGT expressed in S. cerevisiae showed a catalytic activity during in vitro assays using casein kinase II substrates, whereas no such activity was obtained in rYlOGT. 27687229 0 56 dep human 35:39 arg1 transferases 74:85 O-GlcNAc transferases 65:85 O-GlcNAc transferases 65:85 Functional analysis of recombinant human and Yarrowia lipolytica O-GlcNAc transferases expressed in Saccharomyces cerevisiae. 27687229 9 57 theme fungal 1589:1594 arg1 OGT 1596:1598 the fungal OGT 1585:1598 the fungal OGT 1585:1598 This is the first report on the functional analysis of the fungal OGT, indicating that the Y. lipolytica OGT retains its catalytic activity, although the physiological role and substrates of YlOGT remain to be elucidated. 27687229 4 58 theme recombinant 802:812 arg1 YlOGT 814:818 the recombinant YlOGT 798:818 the recombinant YlOGT (rYlOGT) 798:827 Immunoblotting assays using antibody against O-GlcNAc revealed that recombinant hOGT (rhOGT), but not the recombinant YlOGT (rYlOGT), undergoes auto-O-GlcNAcylation in the heterologous host S. cerevisiae. 27687229 4 58 theme recombinant 802:812 arg1 rYlOGT 821:826 rYlOGT 821:826 rYlOGT 821:826 Immunoblotting assays using antibody against O-GlcNAc revealed that recombinant hOGT (rhOGT), but not the recombinant YlOGT (rYlOGT), undergoes auto-O-GlcNAcylation in the heterologous host S. cerevisiae. 27687229 4 59 theme Immunoblotting 696:709 arg1 assays 711:716 Immunoblotting assays 696:716 Immunoblotting assays using antibody against O-GlcNAc 696:748 Immunoblotting assays using antibody against O-GlcNAc revealed that recombinant hOGT (rhOGT), but not the recombinant YlOGT (rYlOGT), undergoes auto-O-GlcNAcylation in the heterologous host S. cerevisiae. 27687229 1 60 theme O-GlcNAc 158:165 arg1 modification 217:228 an important post-translational modification 185:228 an important post-translational modification in many cellular processes 185:255 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation is an important post-translational modification in many cellular processes. 27687229 1 60 theme O-GlcNAc 158:165 arg1 glycosylation 168:180 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation 126:180 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation 126:180 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation is an important post-translational modification in many cellular processes. 27687229 9 61 theme physiological 1684:1696 arg1 role 1698:1701 the physiological role 1680:1701 the physiological role 1680:1701 This is the first report on the functional analysis of the fungal OGT, indicating that the Y. lipolytica OGT retains its catalytic activity, although the physiological role and substrates of YlOGT remain to be elucidated. 27687229 8 62 theme CTD 1460:1462 arg1 fragment 1464:1471 only the CTD fragment 1451:1471 only the CTD fragment 1451:1471 Although the overexpression of full-length OGTs inhibited the growth of S. cerevisiae, no such inhibition was obtained upon overexpression of only the CTD fragment, indicating the role of TPR domain in growth inhibition. 27687229 5 63 theme casein 1005:1010 arg1 kinase 1012:1017 casein kinase II 1005:1020 casein kinase II substrates 1005:1031 Moreover, the rhOGT expressed in S. cerevisiae showed a catalytic activity during in vitro assays using casein kinase II substrates, whereas no such activity was obtained in rYlOGT. 27687229 3 64 theme only 478:481 arg1 homolog 483:489 the only homolog 474:489 the only homolog identified in the subphylum Saccharomycotina through bioinformatics analysis 474:566 In this study, we expressed a putative Yarrowia lipolytica OGT (YlOGT), the only homolog identified in the subphylum Saccharomycotina through bioinformatics analysis, and the human OGT (hOGT) as recombinant proteins in Saccharomyces cerevisiae, and performed their functional characterization. 27687229 3 64 theme only 478:481 arg1 proteins 609:616 recombinant proteins 597:616 recombinant proteins in Saccharomyces cerevisiae 597:644 In this study, we expressed a putative Yarrowia lipolytica OGT (YlOGT), the only homolog identified in the subphylum Saccharomycotina through bioinformatics analysis, and the human OGT (hOGT) as recombinant proteins in Saccharomyces cerevisiae, and performed their functional characterization. 27687229 3 64 theme only 478:481 arg1 OGT 461:463 a putative Yarrowia lipolytica OGT 430:463 a putative Yarrowia lipolytica OGT (YlOGT) 430:471 In this study, we expressed a putative Yarrowia lipolytica OGT (YlOGT), the only homolog identified in the subphylum Saccharomycotina through bioinformatics analysis, and the human OGT (hOGT) as recombinant proteins in Saccharomyces cerevisiae, and performed their functional characterization. 27687229 3 64 theme only 478:481 arg1 OGT 583:585 the human OGT 573:585 the human OGT (hOGT) 573:592 In this study, we expressed a putative Yarrowia lipolytica OGT (YlOGT), the only homolog identified in the subphylum Saccharomycotina through bioinformatics analysis, and the human OGT (hOGT) as recombinant proteins in Saccharomyces cerevisiae, and performed their functional characterization. 27687229 7 65 theme in 1292:1293 arg1 assays 1301:1306 the in vitro assays 1288:1306 the in vitro assays 1288:1306 lipolytica OGT, carrying the human tetratricopeptide repeat (TPR) domain along with the Y. lipolytica catalytic domain (CTD), mediated the transfer of O-GlcNAc moiety during the in vitro assays. 27687229 7 66 theme catalytic 1216:1224 arg1 CTD 1234:1236 CTD 1234:1236 CTD 1234:1236 lipolytica OGT, carrying the human tetratricopeptide repeat (TPR) domain along with the Y. lipolytica catalytic domain (CTD), mediated the transfer of O-GlcNAc moiety during the in vitro assays. 27687229 7 66 theme catalytic 1216:1224 arg1 domain 1226:1231 the Y. lipolytica catalytic domain 1198:1231 the human tetratricopeptide repeat (TPR) domain along with the Y. lipolytica catalytic domain (CTD) 1139:1237 lipolytica OGT, carrying the human tetratricopeptide repeat (TPR) domain along with the Y. lipolytica catalytic domain (CTD), mediated the transfer of O-GlcNAc moiety during the in vitro assays. 27687229 3 67 theme functional 667:676 arg1 characterization 678:693 their functional characterization 661:693 their functional characterization 661:693 In this study, we expressed a putative Yarrowia lipolytica OGT (YlOGT), the only homolog identified in the subphylum Saccharomycotina through bioinformatics analysis, and the human OGT (hOGT) as recombinant proteins in Saccharomyces cerevisiae, and performed their functional characterization. 27687229 3 68 theme recombinant 597:607 arg1 homolog 483:489 the only homolog 474:489 the only homolog identified in the subphylum Saccharomycotina through bioinformatics analysis 474:566 In this study, we expressed a putative Yarrowia lipolytica OGT (YlOGT), the only homolog identified in the subphylum Saccharomycotina through bioinformatics analysis, and the human OGT (hOGT) as recombinant proteins in Saccharomyces cerevisiae, and performed their functional characterization. 27687229 3 68 theme recombinant 597:607 arg1 proteins 609:616 recombinant proteins 597:616 recombinant proteins in Saccharomyces cerevisiae 597:644 In this study, we expressed a putative Yarrowia lipolytica OGT (YlOGT), the only homolog identified in the subphylum Saccharomycotina through bioinformatics analysis, and the human OGT (hOGT) as recombinant proteins in Saccharomyces cerevisiae, and performed their functional characterization. 27687229 3 68 theme recombinant 597:607 arg1 OGT 461:463 a putative Yarrowia lipolytica OGT 430:463 a putative Yarrowia lipolytica OGT (YlOGT) 430:471 In this study, we expressed a putative Yarrowia lipolytica OGT (YlOGT), the only homolog identified in the subphylum Saccharomycotina through bioinformatics analysis, and the human OGT (hOGT) as recombinant proteins in Saccharomyces cerevisiae, and performed their functional characterization. 27687229 3 68 theme recombinant 597:607 arg1 OGT 583:585 the human OGT 573:585 the human OGT (hOGT) 573:592 In this study, we expressed a putative Yarrowia lipolytica OGT (YlOGT), the only homolog identified in the subphylum Saccharomycotina through bioinformatics analysis, and the human OGT (hOGT) as recombinant proteins in Saccharomyces cerevisiae, and performed their functional characterization. 27687229 2 69 theme proteins 392:399 arg1 threonine 359:367 threonine 359:367 threonine 359:367 It is mediated by O-GlcNAc transferases (OGTs), which catalyze the addition of O-GlcNAc to serine or threonine residues of the target proteins. 27687229 2 69 theme proteins 392:399 arg1 serine 349:354 serine 349:354 serine 349:354 It is mediated by O-GlcNAc transferases (OGTs), which catalyze the addition of O-GlcNAc to serine or threonine residues of the target proteins. 27687229 1 70 link O-linked 126:133 arg1 modification 217:228 an important post-translational modification 185:228 an important post-translational modification in many cellular processes 185:255 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation is an important post-translational modification in many cellular processes. 27687229 1 70 link O-linked 126:133 arg1 glycosylation 168:180 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation 126:180 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation 126:180 O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation is an important post-translational modification in many cellular processes. 27687229 8 71 theme such 1399:1402 arg1 inhibition 1404:1413 no such inhibition 1396:1413 no such inhibition 1396:1413 Although the overexpression of full-length OGTs inhibited the growth of S. cerevisiae, no such inhibition was obtained upon overexpression of only the CTD fragment, indicating the role of TPR domain in growth inhibition. 27687229 4 72 dep S. 886:887 arg1 cerevisiae 889:898 cerevisiae 889:898 cerevisiae 889:898 Immunoblotting assays using antibody against O-GlcNAc revealed that recombinant hOGT (rhOGT), but not the recombinant YlOGT (rYlOGT), undergoes auto-O-GlcNAcylation in the heterologous host S. cerevisiae. 27687229 2 73 theme target 385:390 arg1 proteins 392:399 the target proteins 381:399 the target proteins 381:399 It is mediated by O-GlcNAc transferases (OGTs), which catalyze the addition of O-GlcNAc to serine or threonine residues of the target proteins. 27520373 9 0 theme model 1337:1341 arg1 mice 1349:1352 the pathophysiological model ob/ob mice 1314:1352 the pathophysiological model ob/ob mice 1314:1352 We demonstrated that endogenous GCK expression correlated with O-GlcNAc levels in the pathophysiological model ob/ob mice. 27520373 7 1 theme key 1017:1019 arg1 proteins 1032:1039 key regulatory proteins 1017:1039 key regulatory proteins 1017:1039 The post-translational O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) acts as a glucose-sensitive modification and is believed to take part in hepatic glucose sensing by modifying key regulatory proteins. 27520373 7 2 theme glucose-sensitive 917:933 arg1 β-N-acetylglucosaminylation 861:887 The post-translational O-linked β-N-acetylglucosaminylation 829:887 The post-translational O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) 829:905 The post-translational O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) acts as a glucose-sensitive modification and is believed to take part in hepatic glucose sensing by modifying key regulatory proteins. 27520373 7 2 theme glucose-sensitive 917:933 arg1 modification 935:946 a glucose-sensitive modification 915:946 a glucose-sensitive modification 915:946 The post-translational O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) acts as a glucose-sensitive modification and is believed to take part in hepatic glucose sensing by modifying key regulatory proteins. 27520373 9 3 from levels 1304:1309 arg1 mice 1349:1352 the pathophysiological model ob/ob mice 1314:1352 the pathophysiological model ob/ob mice 1314:1352 We demonstrated that endogenous GCK expression correlated with O-GlcNAc levels in the pathophysiological model ob/ob mice. 27520373 9 4 theme ob/ob 1343:1347 arg1 mice 1349:1352 the pathophysiological model ob/ob mice 1314:1352 the pathophysiological model ob/ob mice 1314:1352 We demonstrated that endogenous GCK expression correlated with O-GlcNAc levels in the pathophysiological model ob/ob mice. 27520373 13 5 theme in vitro 1768:1775 arg1 results 1777:1783 our in vivo and in vitro results 1752:1783 results 1777:1783 Altogether, our in vivo and in vitro results demonstrate that GCK expression is regulated by nutrient-sensing O-GlcNAc cycling in liver. 27520373 7 6 theme regulatory 1021:1030 arg1 proteins 1032:1039 key regulatory proteins 1017:1039 key regulatory proteins 1017:1039 The post-translational O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) acts as a glucose-sensitive modification and is believed to take part in hepatic glucose sensing by modifying key regulatory proteins. 27520373 11 7 theme GlcNAc 1478:1483 arg1 succinylated-WGA 1501:1516 the GlcNAc specific lectin succinylated-WGA 1474:1516 the GlcNAc specific lectin succinylated-WGA 1474:1516 Using the GlcNAc specific lectin succinylated-WGA and click chemistry labeling approaches, we demonstrated that GCK is modified by O-GlcNAcylation. 27520373 7 8 link O-linked 852:859 arg1 O-GlcNAcylation 890:904 O-GlcNAcylation 890:904 O-GlcNAcylation 890:904 The post-translational O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) acts as a glucose-sensitive modification and is believed to take part in hepatic glucose sensing by modifying key regulatory proteins. 27520373 7 8 link O-linked 852:859 arg1 modification 935:946 a glucose-sensitive modification 915:946 a glucose-sensitive modification 915:946 The post-translational O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) acts as a glucose-sensitive modification and is believed to take part in hepatic glucose sensing by modifying key regulatory proteins. 27520373 7 8 link O-linked 852:859 arg1 β-N-acetylglucosaminylation 861:887 The post-translational O-linked β-N-acetylglucosaminylation 829:887 The post-translational O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) 829:905 The post-translational O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) acts as a glucose-sensitive modification and is believed to take part in hepatic glucose sensing by modifying key regulatory proteins. 27520373 12 9 theme protein 1725:1731 arg1 level 1733:1737 GCK protein level 1721:1737 O-GlcNAc content but also GCK protein level 1695:1737 Further, we demonstrated that siRNA-mediated Ogt knock-down not only decreases O-GlcNAc content but also GCK protein level. 27520373 6 10 theme regulatory 808:817 arg1 proteins 819:826 regulatory proteins 808:826 regulatory proteins 808:826 In liver, simultaneous increase of glucose and insulin enhances GCK activity and gene expression, changes its subcellular location and interaction with regulatory proteins. 27520373 10 11 theme pharmacological 1393:1407 arg1 inhibition 1409:1418 the pharmacological inhibition 1389:1418 the pharmacological inhibition of O-GlcNAcase 1389:1433 More specifically, in response to the pharmacological inhibition of O-GlcNAcase (OGA) contents of GCK increased. 27520373 3 12 theme glucose 333:339 arg1 flux 313:316 the flux 309:316 the flux 309:316 Glucokinase (GCK) or hexokinase IV, is the main enzyme that regulates the flux and the use of glucose in the liver leading to a compensation of hyperglycemia. 27520373 3 12 theme glucose 333:339 arg1 use 326:328 the use 322:328 the use of glucose in the liver leading to a compensation of hyperglycemia 322:395 Glucokinase (GCK) or hexokinase IV, is the main enzyme that regulates the flux and the use of glucose in the liver leading to a compensation of hyperglycemia. 27520373 2 13 theme functions 155:163 arg1 One 136:138 One 136:138 One 136:138 One of the liver's functions is to maintain blood glucose concentrations within a physiological range. 27520373 2 13 theme functions 155:163 arg1 functions 155:163 the liver's functions 143:163 the liver's functions 143:163 One of the liver's functions is to maintain blood glucose concentrations within a physiological range. 27520373 12 14 dep knock-down 1665:1674 arg1 only 1680:1683 only 1680:1683 only 1680:1683 Further, we demonstrated that siRNA-mediated Ogt knock-down not only decreases O-GlcNAc content but also GCK protein level. 27520373 5 15 theme glycogen 591:598 arg1 synthesis 600:608 glycogen synthesis 591:608 glycogen synthesis 591:608 This critical enzymatic reaction is determinant for the metabolism of glucose in the liver which includes glycogen synthesis, glycolysis, lipogenesis and gluconeogenesis. 27520373 6 16 theme insulin 703:709 arg1 increase 679:686 simultaneous increase 666:686 simultaneous increase of glucose and insulin 666:709 In liver, simultaneous increase of glucose and insulin enhances GCK activity and gene expression, changes its subcellular location and interaction with regulatory proteins. 27520373 10 17 dep inhibition 1409:1418 arg1 response 1377:1384 response 1377:1384 response 1377:1384 More specifically, in response to the pharmacological inhibition of O-GlcNAcase (OGA) contents of GCK increased. 27520373 7 18 theme glucose 988:994 arg1 sensing 996:1002 hepatic glucose sensing 980:1002 hepatic glucose sensing 980:1002 The post-translational O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) acts as a glucose-sensitive modification and is believed to take part in hepatic glucose sensing by modifying key regulatory proteins. 27520373 1 19 theme Blood 79:83 arg1 glucose 85:91 Blood glucose 79:91 Blood glucose 79:91 Blood glucose fluctuates with the fasting-feeding cycle. 27520373 11 20 theme specific 1485:1492 arg1 succinylated-WGA 1501:1516 the GlcNAc specific lectin succinylated-WGA 1474:1516 the GlcNAc specific lectin succinylated-WGA 1474:1516 Using the GlcNAc specific lectin succinylated-WGA and click chemistry labeling approaches, we demonstrated that GCK is modified by O-GlcNAcylation. 27520373 5 21 theme glucose 555:561 arg1 metabolism 541:550 the metabolism 537:550 the metabolism of glucose in the liver which includes glycogen synthesis, glycolysis, lipogenesis and gluconeogenesis 537:653 This critical enzymatic reaction is determinant for the metabolism of glucose in the liver which includes glycogen synthesis, glycolysis, lipogenesis and gluconeogenesis. 27520373 6 22 with interaction 791:801 arg1 proteins 819:826 regulatory proteins 808:826 regulatory proteins 808:826 In liver, simultaneous increase of glucose and insulin enhances GCK activity and gene expression, changes its subcellular location and interaction with regulatory proteins. 27520373 6 23 theme glucose 691:697 arg1 increase 679:686 simultaneous increase 666:686 simultaneous increase of glucose and insulin 666:709 In liver, simultaneous increase of glucose and insulin enhances GCK activity and gene expression, changes its subcellular location and interaction with regulatory proteins. 27520373 7 24 theme hepatic 980:986 arg1 sensing 996:1002 hepatic glucose sensing 980:1002 hepatic glucose sensing 980:1002 The post-translational O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) acts as a glucose-sensitive modification and is believed to take part in hepatic glucose sensing by modifying key regulatory proteins. 27520373 4 25 theme glucose 451:457 arg1 phosphorylation 432:446 the phosphorylation 428:446 the phosphorylation of glucose 428:457 In hepatocytes, GCK catalyzes the phosphorylation of glucose into glucose-6-phosphate. 27520373 11 26 mod modified 1587:1594 arg3 O-GlcNAcylation 1599:1613 O-GlcNAcylation 1599:1613 O-GlcNAcylation 1599:1613 Using the GlcNAc specific lectin succinylated-WGA and click chemistry labeling approaches, we demonstrated that GCK is modified by O-GlcNAcylation. 27520373 11 26 mod modified 1587:1594 arg1 GCK 1580:1582 GCK 1580:1582 GCK 1580:1582 Using the GlcNAc specific lectin succinylated-WGA and click chemistry labeling approaches, we demonstrated that GCK is modified by O-GlcNAcylation. 27520373 5 27 theme critical 490:497 arg1 reaction 509:516 This critical enzymatic reaction 485:516 This critical enzymatic reaction 485:516 This critical enzymatic reaction is determinant for the metabolism of glucose in the liver which includes glycogen synthesis, glycolysis, lipogenesis and gluconeogenesis. 27520373 3 28 theme hyperglycemia 383:395 arg1 compensation 367:378 a compensation 365:378 a compensation of hyperglycemia 365:395 Glucokinase (GCK) or hexokinase IV, is the main enzyme that regulates the flux and the use of glucose in the liver leading to a compensation of hyperglycemia. 27520373 0 29 theme Glucokinase 0:10 arg1 expression 12:21 Glucokinase expression 0:21 Glucokinase expression 0:21 Glucokinase expression is regulated by glucose through O-GlcNAc glycosylation. 27520373 6 30 theme subcellular 766:776 arg1 location 778:785 its subcellular location 762:785 its subcellular location 762:785 In liver, simultaneous increase of glucose and insulin enhances GCK activity and gene expression, changes its subcellular location and interaction with regulatory proteins. 27520373 7 31 theme post-translational 833:850 arg1 O-GlcNAcylation 890:904 O-GlcNAcylation 890:904 O-GlcNAcylation 890:904 The post-translational O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) acts as a glucose-sensitive modification and is believed to take part in hepatic glucose sensing by modifying key regulatory proteins. 27520373 7 31 theme post-translational 833:850 arg1 modification 935:946 a glucose-sensitive modification 915:946 a glucose-sensitive modification 915:946 The post-translational O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) acts as a glucose-sensitive modification and is believed to take part in hepatic glucose sensing by modifying key regulatory proteins. 27520373 7 31 theme post-translational 833:850 arg1 β-N-acetylglucosaminylation 861:887 The post-translational O-linked β-N-acetylglucosaminylation 829:887 The post-translational O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) 829:905 The post-translational O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) acts as a glucose-sensitive modification and is believed to take part in hepatic glucose sensing by modifying key regulatory proteins. 27520373 13 32 theme nutrient-sensing 1833:1848 arg1 cycling 1859:1865 nutrient-sensing O-GlcNAc cycling 1833:1865 nutrient-sensing O-GlcNAc cycling in liver 1833:1874 Altogether, our in vivo and in vitro results demonstrate that GCK expression is regulated by nutrient-sensing O-GlcNAc cycling in liver. 27520373 10 33 theme GCK 1453:1455 arg1 contents 1441:1448 in response to the pharmacological inhibition of O-GlcNAcase (OGA) contents 1374:1448 in response to the pharmacological inhibition of O-GlcNAcase (OGA) contents of GCK 1374:1455 More specifically, in response to the pharmacological inhibition of O-GlcNAcase (OGA) contents of GCK increased. 27520373 10 33 theme GCK 1453:1455 arg1 OGA 1436:1438 OGA 1436:1438 OGA 1436:1438 More specifically, in response to the pharmacological inhibition of O-GlcNAcase (OGA) contents of GCK increased. 27520373 8 34 mod modified 1090:1097 arg3 O-GlcNAcylation 1102:1116 O-GlcNAcylation 1102:1116 O-GlcNAcylation 1102:1116 Therefore, we aimed to determine whether GCK is modified by O-GlcNAcylation in the liver of mice and investigated the role that this modification plays in regulating GCK protein expression. 27520373 8 34 mod modified 1090:1097 arg1 GCK 1083:1085 GCK 1083:1085 GCK 1083:1085 Therefore, we aimed to determine whether GCK is modified by O-GlcNAcylation in the liver of mice and investigated the role that this modification plays in regulating GCK protein expression. 27520373 9 35 theme endogenous 1253:1262 arg1 expression 1268:1277 endogenous GCK expression 1253:1277 endogenous GCK expression 1253:1277 We demonstrated that endogenous GCK expression correlated with O-GlcNAc levels in the pathophysiological model ob/ob mice. 27520373 6 36 theme simultaneous 666:677 arg1 increase 679:686 simultaneous increase 666:686 simultaneous increase of glucose and insulin 666:709 In liver, simultaneous increase of glucose and insulin enhances GCK activity and gene expression, changes its subcellular location and interaction with regulatory proteins. 27520373 5 37 from metabolism 541:550 arg1 gluconeogenesis 639:653 gluconeogenesis 639:653 gluconeogenesis 639:653 This critical enzymatic reaction is determinant for the metabolism of glucose in the liver which includes glycogen synthesis, glycolysis, lipogenesis and gluconeogenesis. 27520373 5 37 from metabolism 541:550 arg1 lipogenesis 623:633 lipogenesis 623:633 lipogenesis 623:633 This critical enzymatic reaction is determinant for the metabolism of glucose in the liver which includes glycogen synthesis, glycolysis, lipogenesis and gluconeogenesis. 27520373 5 37 from metabolism 541:550 arg1 liver 570:574 the liver 566:574 the liver which includes glycogen synthesis 566:608 This critical enzymatic reaction is determinant for the metabolism of glucose in the liver which includes glycogen synthesis, glycolysis, lipogenesis and gluconeogenesis. 27520373 5 37 from metabolism 541:550 arg1 glycolysis 611:620 glycolysis 611:620 glycolysis 611:620 This critical enzymatic reaction is determinant for the metabolism of glucose in the liver which includes glycogen synthesis, glycolysis, lipogenesis and gluconeogenesis. 27520373 13 38 theme O-GlcNAc 1850:1857 arg1 cycling 1859:1865 nutrient-sensing O-GlcNAc cycling 1833:1865 nutrient-sensing O-GlcNAc cycling in liver 1833:1874 Altogether, our in vivo and in vitro results demonstrate that GCK expression is regulated by nutrient-sensing O-GlcNAc cycling in liver. 27520373 2 39 theme blood 180:184 arg1 concentrations 194:207 blood glucose concentrations 180:207 blood glucose concentrations 180:207 One of the liver's functions is to maintain blood glucose concentrations within a physiological range. 27520373 1 40 theme fasting-feeding 113:127 arg1 cycle 129:133 the fasting-feeding cycle 109:133 the fasting-feeding cycle 109:133 Blood glucose fluctuates with the fasting-feeding cycle. 27520373 11 41 theme lectin 1494:1499 arg1 succinylated-WGA 1501:1516 the GlcNAc specific lectin succinylated-WGA 1474:1516 the GlcNAc specific lectin succinylated-WGA 1474:1516 Using the GlcNAc specific lectin succinylated-WGA and click chemistry labeling approaches, we demonstrated that GCK is modified by O-GlcNAcylation. 27520373 12 42 theme GCK 1721:1723 arg1 level 1733:1737 GCK protein level 1721:1737 O-GlcNAc content but also GCK protein level 1695:1737 Further, we demonstrated that siRNA-mediated Ogt knock-down not only decreases O-GlcNAc content but also GCK protein level. 27520373 3 43 from use 326:328 arg1 liver 348:352 the liver 344:352 the liver leading to a compensation of hyperglycemia 344:395 Glucokinase (GCK) or hexokinase IV, is the main enzyme that regulates the flux and the use of glucose in the liver leading to a compensation of hyperglycemia. 27520373 13 44 theme GCK 1802:1804 arg1 expression 1806:1815 GCK expression 1802:1815 GCK expression 1802:1815 Altogether, our in vivo and in vitro results demonstrate that GCK expression is regulated by nutrient-sensing O-GlcNAc cycling in liver. 27520373 13 45 from cycling 1859:1865 arg1 liver 1870:1874 liver 1870:1874 liver 1870:1874 Altogether, our in vivo and in vitro results demonstrate that GCK expression is regulated by nutrient-sensing O-GlcNAc cycling in liver. 27520373 0 46 theme O-GlcNAc 55:62 arg1 glycosylation 64:76 O-GlcNAc glycosylation 55:76 O-GlcNAc glycosylation 55:76 Glucokinase expression is regulated by glucose through O-GlcNAc glycosylation. 27520373 8 47 theme mice 1134:1137 arg1 liver 1125:1129 the liver 1121:1129 the liver of mice 1121:1137 Therefore, we aimed to determine whether GCK is modified by O-GlcNAcylation in the liver of mice and investigated the role that this modification plays in regulating GCK protein expression. 27520373 10 48 theme O-GlcNAcase 1423:1433 arg1 inhibition 1409:1418 the pharmacological inhibition 1389:1418 the pharmacological inhibition of O-GlcNAcase 1389:1433 More specifically, in response to the pharmacological inhibition of O-GlcNAcase (OGA) contents of GCK increased. 27520373 6 49 with location 778:785 arg1 proteins 819:826 regulatory proteins 808:826 regulatory proteins 808:826 In liver, simultaneous increase of glucose and insulin enhances GCK activity and gene expression, changes its subcellular location and interaction with regulatory proteins. 27520373 12 50 theme Ogt 1661:1663 arg1 knock-down 1665:1674 siRNA-mediated Ogt knock-down 1646:1674 siRNA-mediated Ogt knock-down 1646:1674 Further, we demonstrated that siRNA-mediated Ogt knock-down not only decreases O-GlcNAc content but also GCK protein level. 27520373 9 51 theme O-GlcNAc 1295:1302 arg1 levels 1304:1309 O-GlcNAc levels 1295:1309 O-GlcNAc levels in the pathophysiological model ob/ob mice 1295:1352 We demonstrated that endogenous GCK expression correlated with O-GlcNAc levels in the pathophysiological model ob/ob mice. 27520373 2 52 theme physiological 218:230 arg1 range 232:236 a physiological range 216:236 a physiological range 216:236 One of the liver's functions is to maintain blood glucose concentrations within a physiological range. 27520373 12 53 theme siRNA-mediated 1646:1659 arg1 knock-down 1665:1674 siRNA-mediated Ogt knock-down 1646:1674 siRNA-mediated Ogt knock-down 1646:1674 Further, we demonstrated that siRNA-mediated Ogt knock-down not only decreases O-GlcNAc content but also GCK protein level. 27520373 12 54 theme O-GlcNAc 1695:1702 arg1 content 1704:1710 O-GlcNAc content 1695:1710 O-GlcNAc content but also GCK protein level 1695:1737 Further, we demonstrated that siRNA-mediated Ogt knock-down not only decreases O-GlcNAc content but also GCK protein level. 27520373 6 55 theme gene 737:740 arg1 expression 742:751 gene expression 737:751 gene expression 737:751 In liver, simultaneous increase of glucose and insulin enhances GCK activity and gene expression, changes its subcellular location and interaction with regulatory proteins. 27520373 6 56 dep enhances 711:718 arg1 changes 754:760 changes 754:760 changes its subcellular location and interaction with regulatory proteins 754:826 In liver, simultaneous increase of glucose and insulin enhances GCK activity and gene expression, changes its subcellular location and interaction with regulatory proteins. 27520373 3 57 theme main 282:285 arg1 hexokinase 260:269 hexokinase IV 260:272 hexokinase IV 260:272 Glucokinase (GCK) or hexokinase IV, is the main enzyme that regulates the flux and the use of glucose in the liver leading to a compensation of hyperglycemia. 27520373 3 57 theme main 282:285 arg1 Glucokinase 239:249 Glucokinase 239:249 Glucokinase (GCK) 239:255 Glucokinase (GCK) or hexokinase IV, is the main enzyme that regulates the flux and the use of glucose in the liver leading to a compensation of hyperglycemia. 27520373 3 57 theme main 282:285 arg1 enzyme 287:292 the main enzyme 278:292 the main enzyme that regulates the flux and the use of glucose in the liver leading to a compensation of hyperglycemia 278:395 Glucokinase (GCK) or hexokinase IV, is the main enzyme that regulates the flux and the use of glucose in the liver leading to a compensation of hyperglycemia. 27520373 3 58 from flux 313:316 arg1 liver 348:352 the liver 344:352 the liver leading to a compensation of hyperglycemia 344:395 Glucokinase (GCK) or hexokinase IV, is the main enzyme that regulates the flux and the use of glucose in the liver leading to a compensation of hyperglycemia. 27520373 8 59 theme GCK 1208:1210 arg1 expression 1220:1229 GCK protein expression 1208:1229 GCK protein expression 1208:1229 Therefore, we aimed to determine whether GCK is modified by O-GlcNAcylation in the liver of mice and investigated the role that this modification plays in regulating GCK protein expression. 27520373 5 60 theme enzymatic 499:507 arg1 reaction 509:516 This critical enzymatic reaction 485:516 This critical enzymatic reaction 485:516 This critical enzymatic reaction is determinant for the metabolism of glucose in the liver which includes glycogen synthesis, glycolysis, lipogenesis and gluconeogenesis. 27520373 7 61 theme O-linked 852:859 arg1 O-GlcNAcylation 890:904 O-GlcNAcylation 890:904 O-GlcNAcylation 890:904 The post-translational O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) acts as a glucose-sensitive modification and is believed to take part in hepatic glucose sensing by modifying key regulatory proteins. 27520373 7 61 theme O-linked 852:859 arg1 modification 935:946 a glucose-sensitive modification 915:946 a glucose-sensitive modification 915:946 The post-translational O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) acts as a glucose-sensitive modification and is believed to take part in hepatic glucose sensing by modifying key regulatory proteins. 27520373 7 61 theme O-linked 852:859 arg1 β-N-acetylglucosaminylation 861:887 The post-translational O-linked β-N-acetylglucosaminylation 829:887 The post-translational O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) 829:905 The post-translational O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) acts as a glucose-sensitive modification and is believed to take part in hepatic glucose sensing by modifying key regulatory proteins. 27520373 11 62 theme chemistry 1528:1536 arg1 approaches 1547:1556 chemistry labeling approaches 1528:1556 chemistry labeling approaches 1528:1556 Using the GlcNAc specific lectin succinylated-WGA and click chemistry labeling approaches, we demonstrated that GCK is modified by O-GlcNAcylation. 27520373 2 63 theme glucose 186:192 arg1 concentrations 194:207 blood glucose concentrations 180:207 blood glucose concentrations 180:207 One of the liver's functions is to maintain blood glucose concentrations within a physiological range. 27520373 9 64 theme GCK 1264:1266 arg1 expression 1268:1277 endogenous GCK expression 1253:1277 endogenous GCK expression 1253:1277 We demonstrated that endogenous GCK expression correlated with O-GlcNAc levels in the pathophysiological model ob/ob mice. 27520373 11 65 dep succinylated-WGA 1501:1516 arg1 approaches 1547:1556 chemistry labeling approaches 1528:1556 chemistry labeling approaches 1528:1556 Using the GlcNAc specific lectin succinylated-WGA and click chemistry labeling approaches, we demonstrated that GCK is modified by O-GlcNAcylation. 27520373 11 66 theme labeling 1538:1545 arg1 approaches 1547:1556 chemistry labeling approaches 1528:1556 chemistry labeling approaches 1528:1556 Using the GlcNAc specific lectin succinylated-WGA and click chemistry labeling approaches, we demonstrated that GCK is modified by O-GlcNAcylation. 27520373 9 67 theme pathophysiological 1318:1335 arg1 mice 1349:1352 the pathophysiological model ob/ob mice 1314:1352 the pathophysiological model ob/ob mice 1314:1352 We demonstrated that endogenous GCK expression correlated with O-GlcNAc levels in the pathophysiological model ob/ob mice. 27520373 6 68 theme GCK 720:722 arg1 activity 724:731 GCK activity 720:731 GCK activity 720:731 In liver, simultaneous increase of glucose and insulin enhances GCK activity and gene expression, changes its subcellular location and interaction with regulatory proteins. 27520373 8 69 theme protein 1212:1218 arg1 expression 1220:1229 GCK protein expression 1208:1229 GCK protein expression 1208:1229 Therefore, we aimed to determine whether GCK is modified by O-GlcNAcylation in the liver of mice and investigated the role that this modification plays in regulating GCK protein expression. 26676748 7 0 theme O-linked 1089:1096 arg1 glycosylation 1098:1110 O-linked glycosylation 1089:1110 O-linked glycosylation of SHH to promote its activation, which was essential for the self-renewal maintenance of BCSCs and bladder tumorigenesis 1089:1232 Mechanistically, GALNT1 mediated O-linked glycosylation of SHH to promote its activation, which was essential for the self-renewal maintenance of BCSCs and bladder tumorigenesis. 26676748 9 1 theme signaling 1533:1541 arg1 inhibition 1504:1513 the inhibition 1500:1513 the inhibition of GALNT1 and SHH signaling 1500:1541 Taken together, our findings identify a BCSC subpopulation in human bladder tumors that appears to be responsive to the inhibition of GALNT1 and SHH signaling, and thus highlight a potential strategy for preventing the rapid recurrence typical in patients with bladder cancer. 26676748 8 2 theme potent 1328:1333 arg1 activity 1345:1352 potent antitumor activity 1328:1352 potent antitumor activity 1328:1352 Finally, intravesical instillation of GALNT1 siRNA and the SHH inhibitor cyclopamine exerted potent antitumor activity against bladder tumor growth. 26676748 2 3 theme stem 353:356 arg1 CSC 364:366 CSC 364:366 CSC 364:366 Sonic Hedgehog (SHH) signaling has been implicated in promoting cancer stem cell (CSC) self-renewal and is activated in bladder cancer, but its impact on BCSC maintenance is unclear. 26676748 2 3 theme stem 353:356 arg1 cell 358:361 cancer stem cell 346:361 cancer stem cell (CSC) 346:367 Sonic Hedgehog (SHH) signaling has been implicated in promoting cancer stem cell (CSC) self-renewal and is activated in bladder cancer, but its impact on BCSC maintenance is unclear. 26676748 1 4 theme tumor 249:253 arg1 initiation 255:264 bladder tumor initiation 241:264 bladder tumor initiation 241:264 The existence of bladder cancer stem cells (BCSC) has been suggested to underlie bladder tumor initiation and recurrence. 26676748 0 5 theme Self-Renewal 87:98 arg1 Capacity 121:128 the Self-Renewal and Tumor-Initiating Capacity 83:128 the Self-Renewal and Tumor-Initiating Capacity of Bladder Cancer Stem Cells 83:157 GALNT1-Mediated Glycosylation and Activation of Sonic Hedgehog Signaling Maintains the Self-Renewal and Tumor-Initiating Capacity of Bladder Cancer Stem Cells. 26676748 9 6 theme potential 1565:1573 arg1 strategy 1575:1582 a potential strategy 1563:1582 a potential strategy for preventing the rapid recurrence typical in patients with bladder cancer 1563:1658 Taken together, our findings identify a BCSC subpopulation in human bladder tumors that appears to be responsive to the inhibition of GALNT1 and SHH signaling, and thus highlight a potential strategy for preventing the rapid recurrence typical in patients with bladder cancer. 26676748 4 7 with combination 610:620 arg1 antibody 650:657 an anti-CD44 antibody 637:657 an anti-CD44 antibody 637:657 The combination of BCMab1 with an anti-CD44 antibody identified a BCMab1(+)CD44(+) cell subpopulation as BCSCs with stem cell-like properties. 26676748 2 8 theme cancer 346:351 arg1 CSC 364:366 CSC 364:366 CSC 364:366 Sonic Hedgehog (SHH) signaling has been implicated in promoting cancer stem cell (CSC) self-renewal and is activated in bladder cancer, but its impact on BCSC maintenance is unclear. 26676748 2 8 theme cancer 346:351 arg1 cell 358:361 cancer stem cell 346:361 cancer stem cell (CSC) 346:367 Sonic Hedgehog (SHH) signaling has been implicated in promoting cancer stem cell (CSC) self-renewal and is activated in bladder cancer, but its impact on BCSC maintenance is unclear. 26676748 3 9 gly glycosylated 578:589 arg1 α3β1 600:603 aberrantly glycosylated integrin α3β1 567:603 aberrantly glycosylated integrin α3β1 567:603 In this study, we generated a mAb (BCMab1) against CD44(+) human bladder cancer cells that recognizes aberrantly glycosylated integrin α3β1. 26676748 8 10 theme inhibitor 1298:1306 arg1 cyclopamine 1308:1318 the SHH inhibitor cyclopamine 1290:1318 the SHH inhibitor cyclopamine 1290:1318 Finally, intravesical instillation of GALNT1 siRNA and the SHH inhibitor cyclopamine exerted potent antitumor activity against bladder tumor growth. 26676748 9 11 from subpopulation 1429:1441 arg1 tumors 1460:1465 human bladder tumors 1446:1465 human bladder tumors 1446:1465 Taken together, our findings identify a BCSC subpopulation in human bladder tumors that appears to be responsive to the inhibition of GALNT1 and SHH signaling, and thus highlight a potential strategy for preventing the rapid recurrence typical in patients with bladder cancer. 26676748 9 12 theme bladder 1452:1458 arg1 tumors 1460:1465 human bladder tumors 1446:1465 human bladder tumors 1446:1465 Taken together, our findings identify a BCSC subpopulation in human bladder tumors that appears to be responsive to the inhibition of GALNT1 and SHH signaling, and thus highlight a potential strategy for preventing the rapid recurrence typical in patients with bladder cancer. 26676748 0 13 theme Tumor-Initiating 104:119 arg1 Capacity 121:128 the Self-Renewal and Tumor-Initiating Capacity 83:128 the Self-Renewal and Tumor-Initiating Capacity of Bladder Cancer Stem Cells 83:157 GALNT1-Mediated Glycosylation and Activation of Sonic Hedgehog Signaling Maintains the Self-Renewal and Tumor-Initiating Capacity of Bladder Cancer Stem Cells. 26676748 6 14 theme clinicopathologic 1009:1025 arg1 features 1027:1034 clinicopathologic features 1009:1034 clinicopathologic features of bladder cancers 1009:1053 Furthermore, the glycotransferase GALNT1 was highly expressed in BCMab1(+)CD44(+) cells and correlated with clinicopathologic features of bladder cancers. 26676748 4 15 theme CD44 681:684 arg1 BCSCs 711:715 BCSCs 711:715 BCSCs with stem cell-like properties 711:746 The combination of BCMab1 with an anti-CD44 antibody identified a BCMab1(+)CD44(+) cell subpopulation as BCSCs with stem cell-like properties. 26676748 4 15 theme CD44 681:684 arg1 subpopulation 694:706 a BCMab1(+)CD44(+) cell subpopulation 670:706 a BCMab1(+)CD44(+) cell subpopulation 670:706 The combination of BCMab1 with an anti-CD44 antibody identified a BCMab1(+)CD44(+) cell subpopulation as BCSCs with stem cell-like properties. 26676748 2 16 theme Hedgehog 288:295 arg1 signaling 303:311 Sonic Hedgehog (SHH) signaling 282:311 Sonic Hedgehog (SHH) signaling 282:311 Sonic Hedgehog (SHH) signaling has been implicated in promoting cancer stem cell (CSC) self-renewal and is activated in bladder cancer, but its impact on BCSC maintenance is unclear. 26676748 0 17 theme Bladder 133:139 arg1 Cells 153:157 Bladder Cancer Stem Cells 133:157 Bladder Cancer Stem Cells 133:157 GALNT1-Mediated Glycosylation and Activation of Sonic Hedgehog Signaling Maintains the Self-Renewal and Tumor-Initiating Capacity of Bladder Cancer Stem Cells. 26676748 2 18 from impact 426:431 arg1 maintenance 441:451 BCSC maintenance 436:451 BCSC maintenance 436:451 Sonic Hedgehog (SHH) signaling has been implicated in promoting cancer stem cell (CSC) self-renewal and is activated in bladder cancer, but its impact on BCSC maintenance is unclear. 26676748 5 19 theme CD44 839:842 arg1 subpopulation 847:859 the BCMab1(+)CD44(+) subpopulation 826:859 the BCMab1(+)CD44(+) subpopulation 826:859 Gene expression analysis revealed that the hedgehog pathway was activated in the BCMab1(+)CD44(+) subpopulation and was required for BCSC self-renewal. 26676748 2 20 theme Sonic 282:286 arg1 Hedgehog 288:295 Sonic Hedgehog 282:295 Sonic Hedgehog (SHH) signaling 282:311 Sonic Hedgehog (SHH) signaling has been implicated in promoting cancer stem cell (CSC) self-renewal and is activated in bladder cancer, but its impact on BCSC maintenance is unclear. 26676748 2 20 theme Sonic 282:286 arg1 SHH 298:300 SHH 298:300 SHH 298:300 Sonic Hedgehog (SHH) signaling has been implicated in promoting cancer stem cell (CSC) self-renewal and is activated in bladder cancer, but its impact on BCSC maintenance is unclear. 26676748 1 21 theme cancer 185:190 arg1 cells 197:201 bladder cancer stem cells 177:201 bladder cancer stem cells (BCSC) 177:208 The existence of bladder cancer stem cells (BCSC) has been suggested to underlie bladder tumor initiation and recurrence. 26676748 1 21 theme cancer 185:190 arg1 BCSC 204:207 BCSC 204:207 BCSC 204:207 The existence of bladder cancer stem cells (BCSC) has been suggested to underlie bladder tumor initiation and recurrence. 26676748 4 22 with BCSCs 711:715 arg1 properties 737:746 stem cell-like properties 722:746 stem cell-like properties 722:746 The combination of BCMab1 with an anti-CD44 antibody identified a BCMab1(+)CD44(+) cell subpopulation as BCSCs with stem cell-like properties. 26676748 9 23 with patients 1631:1638 arg1 cancer 1653:1658 bladder cancer 1645:1658 bladder cancer 1645:1658 Taken together, our findings identify a BCSC subpopulation in human bladder tumors that appears to be responsive to the inhibition of GALNT1 and SHH signaling, and thus highlight a potential strategy for preventing the rapid recurrence typical in patients with bladder cancer. 26676748 1 24 theme stem 192:195 arg1 cells 197:201 bladder cancer stem cells 177:201 bladder cancer stem cells (BCSC) 177:208 The existence of bladder cancer stem cells (BCSC) has been suggested to underlie bladder tumor initiation and recurrence. 26676748 1 24 theme stem 192:195 arg1 BCSC 204:207 BCSC 204:207 BCSC 204:207 The existence of bladder cancer stem cells (BCSC) has been suggested to underlie bladder tumor initiation and recurrence. 26676748 9 25 theme BCSC 1424:1427 arg1 responsive 1486:1495 responsive 1486:1495 responsive 1486:1495 Taken together, our findings identify a BCSC subpopulation in human bladder tumors that appears to be responsive to the inhibition of GALNT1 and SHH signaling, and thus highlight a potential strategy for preventing the rapid recurrence typical in patients with bladder cancer. 26676748 9 25 theme BCSC 1424:1427 arg1 subpopulation 1429:1441 a BCSC subpopulation 1422:1441 a BCSC subpopulation in human bladder tumors that appears to be responsive to the inhibition of GALNT1 and SHH signaling 1422:1541 Taken together, our findings identify a BCSC subpopulation in human bladder tumors that appears to be responsive to the inhibition of GALNT1 and SHH signaling, and thus highlight a potential strategy for preventing the rapid recurrence typical in patients with bladder cancer. 26676748 9 26 from typical 1620:1626 arg1 patients 1631:1638 patients 1631:1638 patients with bladder cancer 1631:1658 Taken together, our findings identify a BCSC subpopulation in human bladder tumors that appears to be responsive to the inhibition of GALNT1 and SHH signaling, and thus highlight a potential strategy for preventing the rapid recurrence typical in patients with bladder cancer. 26676748 8 27 theme siRNA 1280:1284 arg1 instillation 1257:1268 intravesical instillation 1244:1268 intravesical instillation of GALNT1 siRNA 1244:1284 Finally, intravesical instillation of GALNT1 siRNA and the SHH inhibitor cyclopamine exerted potent antitumor activity against bladder tumor growth. 26676748 8 27 theme siRNA 1280:1284 arg1 cyclopamine 1308:1318 the SHH inhibitor cyclopamine 1290:1318 the SHH inhibitor cyclopamine 1290:1318 Finally, intravesical instillation of GALNT1 siRNA and the SHH inhibitor cyclopamine exerted potent antitumor activity against bladder tumor growth. 26676748 7 28 link O-linked 1089:1096 arg1 glycosylation 1098:1110 O-linked glycosylation 1089:1110 O-linked glycosylation of SHH to promote its activation, which was essential for the self-renewal maintenance of BCSCs and bladder tumorigenesis 1089:1232 Mechanistically, GALNT1 mediated O-linked glycosylation of SHH to promote its activation, which was essential for the self-renewal maintenance of BCSCs and bladder tumorigenesis. 26676748 1 29 theme cells 197:201 arg1 existence 164:172 The existence 160:172 The existence of bladder cancer stem cells (BCSC) 160:208 The existence of bladder cancer stem cells (BCSC) has been suggested to underlie bladder tumor initiation and recurrence. 26676748 0 30 theme GALNT1-Mediated 0:14 arg1 Glycosylation 16:28 GALNT1-Mediated Glycosylation 0:28 GALNT1-Mediated Glycosylation 0:28 GALNT1-Mediated Glycosylation and Activation of Sonic Hedgehog Signaling Maintains the Self-Renewal and Tumor-Initiating Capacity of Bladder Cancer Stem Cells. 26676748 9 31 theme rapid 1603:1607 arg1 recurrence 1609:1618 the rapid recurrence 1599:1618 the rapid recurrence typical in patients with bladder cancer 1599:1658 Taken together, our findings identify a BCSC subpopulation in human bladder tumors that appears to be responsive to the inhibition of GALNT1 and SHH signaling, and thus highlight a potential strategy for preventing the rapid recurrence typical in patients with bladder cancer. 26676748 9 32 theme GALNT1 1518:1523 arg1 inhibition 1504:1513 the inhibition 1500:1513 the inhibition of GALNT1 and SHH signaling 1500:1541 Taken together, our findings identify a BCSC subpopulation in human bladder tumors that appears to be responsive to the inhibition of GALNT1 and SHH signaling, and thus highlight a potential strategy for preventing the rapid recurrence typical in patients with bladder cancer. 26676748 3 33 theme CD44 516:519 arg1 cells 545:549 CD44(+) human bladder cancer cells 516:549 CD44(+) human bladder cancer cells 516:549 In this study, we generated a mAb (BCMab1) against CD44(+) human bladder cancer cells that recognizes aberrantly glycosylated integrin α3β1. 26676748 5 34 theme hedgehog 792:799 arg1 pathway 801:807 the hedgehog pathway 788:807 the hedgehog pathway 788:807 Gene expression analysis revealed that the hedgehog pathway was activated in the BCMab1(+)CD44(+) subpopulation and was required for BCSC self-renewal. 26676748 7 35 theme tumorigenesis 1220:1232 arg1 maintenance 1187:1197 the self-renewal maintenance 1170:1197 the self-renewal maintenance of BCSCs and bladder tumorigenesis 1170:1232 Mechanistically, GALNT1 mediated O-linked glycosylation of SHH to promote its activation, which was essential for the self-renewal maintenance of BCSCs and bladder tumorigenesis. 26676748 0 36 theme Stem 148:151 arg1 Cells 153:157 Bladder Cancer Stem Cells 133:157 Bladder Cancer Stem Cells 133:157 GALNT1-Mediated Glycosylation and Activation of Sonic Hedgehog Signaling Maintains the Self-Renewal and Tumor-Initiating Capacity of Bladder Cancer Stem Cells. 26676748 7 37 gly glycosylation 1098:1110 arg1 SHH 1115:1117 SHH 1115:1117 SHH 1115:1117 Mechanistically, GALNT1 mediated O-linked glycosylation of SHH to promote its activation, which was essential for the self-renewal maintenance of BCSCs and bladder tumorigenesis. 26676748 2 38 theme bladder 402:408 arg1 cancer 410:415 bladder cancer 402:415 bladder cancer 402:415 Sonic Hedgehog (SHH) signaling has been implicated in promoting cancer stem cell (CSC) self-renewal and is activated in bladder cancer, but its impact on BCSC maintenance is unclear. 26676748 4 39 theme BCMab1 672:677 arg1 BCSCs 711:715 BCSCs 711:715 BCSCs with stem cell-like properties 711:746 The combination of BCMab1 with an anti-CD44 antibody identified a BCMab1(+)CD44(+) cell subpopulation as BCSCs with stem cell-like properties. 26676748 4 39 theme BCMab1 672:677 arg1 subpopulation 694:706 a BCMab1(+)CD44(+) cell subpopulation 670:706 a BCMab1(+)CD44(+) cell subpopulation 670:706 The combination of BCMab1 with an anti-CD44 antibody identified a BCMab1(+)CD44(+) cell subpopulation as BCSCs with stem cell-like properties. 26676748 0 40 theme Cancer 141:146 arg1 Cells 153:157 Bladder Cancer Stem Cells 133:157 Bladder Cancer Stem Cells 133:157 GALNT1-Mediated Glycosylation and Activation of Sonic Hedgehog Signaling Maintains the Self-Renewal and Tumor-Initiating Capacity of Bladder Cancer Stem Cells. 26676748 3 41 theme glycosylated 578:589 arg1 α3β1 600:603 aberrantly glycosylated integrin α3β1 567:603 aberrantly glycosylated integrin α3β1 567:603 In this study, we generated a mAb (BCMab1) against CD44(+) human bladder cancer cells that recognizes aberrantly glycosylated integrin α3β1. 26676748 1 42 theme bladder 177:183 arg1 cells 197:201 bladder cancer stem cells 177:201 bladder cancer stem cells (BCSC) 177:208 The existence of bladder cancer stem cells (BCSC) has been suggested to underlie bladder tumor initiation and recurrence. 26676748 1 42 theme bladder 177:183 arg1 BCSC 204:207 BCSC 204:207 BCSC 204:207 The existence of bladder cancer stem cells (BCSC) has been suggested to underlie bladder tumor initiation and recurrence. 26676748 5 43 theme Gene 749:752 arg1 analysis 765:772 Gene expression analysis 749:772 Gene expression analysis 749:772 Gene expression analysis revealed that the hedgehog pathway was activated in the BCMab1(+)CD44(+) subpopulation and was required for BCSC self-renewal. 26676748 0 44 theme Sonic 48:52 arg1 Hedgehog 54:61 Sonic Hedgehog 48:61 Sonic Hedgehog Signaling 48:71 GALNT1-Mediated Glycosylation and Activation of Sonic Hedgehog Signaling Maintains the Self-Renewal and Tumor-Initiating Capacity of Bladder Cancer Stem Cells. 26676748 3 45 theme integrin 591:598 arg1 α3β1 600:603 aberrantly glycosylated integrin α3β1 567:603 aberrantly glycosylated integrin α3β1 567:603 In this study, we generated a mAb (BCMab1) against CD44(+) human bladder cancer cells that recognizes aberrantly glycosylated integrin α3β1. 26676748 4 46 theme stem 722:725 arg1 properties 737:746 stem cell-like properties 722:746 stem cell-like properties 722:746 The combination of BCMab1 with an anti-CD44 antibody identified a BCMab1(+)CD44(+) cell subpopulation as BCSCs with stem cell-like properties. 26676748 7 47 theme BCSCs 1202:1206 arg1 maintenance 1187:1197 the self-renewal maintenance 1170:1197 the self-renewal maintenance of BCSCs and bladder tumorigenesis 1170:1232 Mechanistically, GALNT1 mediated O-linked glycosylation of SHH to promote its activation, which was essential for the self-renewal maintenance of BCSCs and bladder tumorigenesis. 26676748 5 48 theme expression 754:763 arg1 analysis 765:772 Gene expression analysis 749:772 Gene expression analysis 749:772 Gene expression analysis revealed that the hedgehog pathway was activated in the BCMab1(+)CD44(+) subpopulation and was required for BCSC self-renewal. 26676748 2 49 theme BCSC 436:439 arg1 maintenance 441:451 BCSC maintenance 436:451 BCSC maintenance 436:451 Sonic Hedgehog (SHH) signaling has been implicated in promoting cancer stem cell (CSC) self-renewal and is activated in bladder cancer, but its impact on BCSC maintenance is unclear. 26676748 0 50 theme Cells 153:157 arg1 Capacity 121:128 the Self-Renewal and Tumor-Initiating Capacity 83:128 the Self-Renewal and Tumor-Initiating Capacity of Bladder Cancer Stem Cells 83:157 GALNT1-Mediated Glycosylation and Activation of Sonic Hedgehog Signaling Maintains the Self-Renewal and Tumor-Initiating Capacity of Bladder Cancer Stem Cells. 26676748 8 51 theme bladder 1362:1368 arg1 growth 1376:1381 bladder tumor growth 1362:1381 bladder tumor growth 1362:1381 Finally, intravesical instillation of GALNT1 siRNA and the SHH inhibitor cyclopamine exerted potent antitumor activity against bladder tumor growth. 26676748 0 52 gly Glycosylation 16:28 arg1 Signaling 63:71 Sonic Hedgehog Signaling 48:71 Sonic Hedgehog Signaling 48:71 GALNT1-Mediated Glycosylation and Activation of Sonic Hedgehog Signaling Maintains the Self-Renewal and Tumor-Initiating Capacity of Bladder Cancer Stem Cells. 26676748 6 53 theme glycotransferase 918:933 arg1 GALNT1 935:940 the glycotransferase GALNT1 914:940 the glycotransferase GALNT1 914:940 Furthermore, the glycotransferase GALNT1 was highly expressed in BCMab1(+)CD44(+) cells and correlated with clinicopathologic features of bladder cancers. 26676748 0 54 theme Signaling 63:71 arg1 Activation 34:43 Activation 34:43 Activation 34:43 GALNT1-Mediated Glycosylation and Activation of Sonic Hedgehog Signaling Maintains the Self-Renewal and Tumor-Initiating Capacity of Bladder Cancer Stem Cells. 26676748 0 54 theme Signaling 63:71 arg1 Glycosylation 16:28 GALNT1-Mediated Glycosylation 0:28 GALNT1-Mediated Glycosylation 0:28 GALNT1-Mediated Glycosylation and Activation of Sonic Hedgehog Signaling Maintains the Self-Renewal and Tumor-Initiating Capacity of Bladder Cancer Stem Cells. 26676748 9 55 theme bladder 1645:1651 arg1 cancer 1653:1658 bladder cancer 1645:1658 bladder cancer 1645:1658 Taken together, our findings identify a BCSC subpopulation in human bladder tumors that appears to be responsive to the inhibition of GALNT1 and SHH signaling, and thus highlight a potential strategy for preventing the rapid recurrence typical in patients with bladder cancer. 26676748 8 56 theme SHH 1294:1296 arg1 cyclopamine 1308:1318 the SHH inhibitor cyclopamine 1290:1318 the SHH inhibitor cyclopamine 1290:1318 Finally, intravesical instillation of GALNT1 siRNA and the SHH inhibitor cyclopamine exerted potent antitumor activity against bladder tumor growth. 26676748 8 57 theme intravesical 1244:1255 arg1 instillation 1257:1268 intravesical instillation 1244:1268 intravesical instillation of GALNT1 siRNA 1244:1284 Finally, intravesical instillation of GALNT1 siRNA and the SHH inhibitor cyclopamine exerted potent antitumor activity against bladder tumor growth. 26676748 0 58 theme Hedgehog 54:61 arg1 Signaling 63:71 Sonic Hedgehog Signaling 48:71 Sonic Hedgehog Signaling 48:71 GALNT1-Mediated Glycosylation and Activation of Sonic Hedgehog Signaling Maintains the Self-Renewal and Tumor-Initiating Capacity of Bladder Cancer Stem Cells. 26676748 6 59 theme cancers 1047:1053 arg1 features 1027:1034 clinicopathologic features 1009:1034 clinicopathologic features of bladder cancers 1009:1053 Furthermore, the glycotransferase GALNT1 was highly expressed in BCMab1(+)CD44(+) cells and correlated with clinicopathologic features of bladder cancers. 26676748 9 60 theme typical 1620:1626 arg1 recurrence 1609:1618 the rapid recurrence 1599:1618 the rapid recurrence typical in patients with bladder cancer 1599:1658 Taken together, our findings identify a BCSC subpopulation in human bladder tumors that appears to be responsive to the inhibition of GALNT1 and SHH signaling, and thus highlight a potential strategy for preventing the rapid recurrence typical in patients with bladder cancer. 26676748 4 61 theme cell-like 727:735 arg1 properties 737:746 stem cell-like properties 722:746 stem cell-like properties 722:746 The combination of BCMab1 with an anti-CD44 antibody identified a BCMab1(+)CD44(+) cell subpopulation as BCSCs with stem cell-like properties. 26676748 7 62 theme bladder 1212:1218 arg1 tumorigenesis 1220:1232 bladder tumorigenesis 1212:1232 bladder tumorigenesis 1212:1232 Mechanistically, GALNT1 mediated O-linked glycosylation of SHH to promote its activation, which was essential for the self-renewal maintenance of BCSCs and bladder tumorigenesis. 26676748 5 63 theme BCMab1 830:835 arg1 subpopulation 847:859 the BCMab1(+)CD44(+) subpopulation 826:859 the BCMab1(+)CD44(+) subpopulation 826:859 Gene expression analysis revealed that the hedgehog pathway was activated in the BCMab1(+)CD44(+) subpopulation and was required for BCSC self-renewal. 26676748 8 64 theme antitumor 1335:1343 arg1 activity 1345:1352 potent antitumor activity 1328:1352 potent antitumor activity 1328:1352 Finally, intravesical instillation of GALNT1 siRNA and the SHH inhibitor cyclopamine exerted potent antitumor activity against bladder tumor growth. 26676748 9 65 theme SHH 1529:1531 arg1 signaling 1533:1541 SHH signaling 1529:1541 SHH signaling 1529:1541 Taken together, our findings identify a BCSC subpopulation in human bladder tumors that appears to be responsive to the inhibition of GALNT1 and SHH signaling, and thus highlight a potential strategy for preventing the rapid recurrence typical in patients with bladder cancer. 26676748 6 66 theme bladder 1039:1045 arg1 cancers 1047:1053 bladder cancers 1039:1053 bladder cancers 1039:1053 Furthermore, the glycotransferase GALNT1 was highly expressed in BCMab1(+)CD44(+) cells and correlated with clinicopathologic features of bladder cancers. 26676748 3 67 theme human 524:528 arg1 cells 545:549 CD44(+) human bladder cancer cells 516:549 CD44(+) human bladder cancer cells 516:549 In this study, we generated a mAb (BCMab1) against CD44(+) human bladder cancer cells that recognizes aberrantly glycosylated integrin α3β1. 26676748 8 68 theme GALNT1 1273:1278 arg1 siRNA 1280:1284 GALNT1 siRNA 1273:1284 GALNT1 siRNA 1273:1284 Finally, intravesical instillation of GALNT1 siRNA and the SHH inhibitor cyclopamine exerted potent antitumor activity against bladder tumor growth. 26676748 4 69 theme cell 689:692 arg1 BCSCs 711:715 BCSCs 711:715 BCSCs with stem cell-like properties 711:746 The combination of BCMab1 with an anti-CD44 antibody identified a BCMab1(+)CD44(+) cell subpopulation as BCSCs with stem cell-like properties. 26676748 4 69 theme cell 689:692 arg1 subpopulation 694:706 a BCMab1(+)CD44(+) cell subpopulation 670:706 a BCMab1(+)CD44(+) cell subpopulation 670:706 The combination of BCMab1 with an anti-CD44 antibody identified a BCMab1(+)CD44(+) cell subpopulation as BCSCs with stem cell-like properties. 26676748 8 70 theme tumor 1370:1374 arg1 growth 1376:1381 bladder tumor growth 1362:1381 bladder tumor growth 1362:1381 Finally, intravesical instillation of GALNT1 siRNA and the SHH inhibitor cyclopamine exerted potent antitumor activity against bladder tumor growth. 26676748 9 71 from patients 1631:1638 arg1 typical 1620:1626 typical 1620:1626 typical 1620:1626 Taken together, our findings identify a BCSC subpopulation in human bladder tumors that appears to be responsive to the inhibition of GALNT1 and SHH signaling, and thus highlight a potential strategy for preventing the rapid recurrence typical in patients with bladder cancer. 26676748 3 72 theme bladder 530:536 arg1 cells 545:549 CD44(+) human bladder cancer cells 516:549 CD44(+) human bladder cancer cells 516:549 In this study, we generated a mAb (BCMab1) against CD44(+) human bladder cancer cells that recognizes aberrantly glycosylated integrin α3β1. 26676748 7 73 theme self-renewal 1174:1185 arg1 maintenance 1187:1197 the self-renewal maintenance 1170:1197 the self-renewal maintenance of BCSCs and bladder tumorigenesis 1170:1232 Mechanistically, GALNT1 mediated O-linked glycosylation of SHH to promote its activation, which was essential for the self-renewal maintenance of BCSCs and bladder tumorigenesis. 26676748 4 74 theme BCMab1 625:630 arg1 combination 610:620 The combination 606:620 The combination of BCMab1 with an anti-CD44 antibody 606:657 The combination of BCMab1 with an anti-CD44 antibody identified a BCMab1(+)CD44(+) cell subpopulation as BCSCs with stem cell-like properties. 26676748 6 75 theme BCMab1 966:971 arg1 cells 983:987 BCMab1(+)CD44(+) cells 966:987 BCMab1(+)CD44(+) cells 966:987 Furthermore, the glycotransferase GALNT1 was highly expressed in BCMab1(+)CD44(+) cells and correlated with clinicopathologic features of bladder cancers. 26676748 9 76 theme human 1446:1450 arg1 tumors 1460:1465 human bladder tumors 1446:1465 human bladder tumors 1446:1465 Taken together, our findings identify a BCSC subpopulation in human bladder tumors that appears to be responsive to the inhibition of GALNT1 and SHH signaling, and thus highlight a potential strategy for preventing the rapid recurrence typical in patients with bladder cancer. 26676748 7 77 theme SHH 1115:1117 arg1 glycosylation 1098:1110 O-linked glycosylation 1089:1110 O-linked glycosylation of SHH to promote its activation, which was essential for the self-renewal maintenance of BCSCs and bladder tumorigenesis 1089:1232 Mechanistically, GALNT1 mediated O-linked glycosylation of SHH to promote its activation, which was essential for the self-renewal maintenance of BCSCs and bladder tumorigenesis. 26676748 3 78 theme cancer 538:543 arg1 cells 545:549 CD44(+) human bladder cancer cells 516:549 CD44(+) human bladder cancer cells 516:549 In this study, we generated a mAb (BCMab1) against CD44(+) human bladder cancer cells that recognizes aberrantly glycosylated integrin α3β1. 26676748 6 79 theme CD44 975:978 arg1 cells 983:987 BCMab1(+)CD44(+) cells 966:987 BCMab1(+)CD44(+) cells 966:987 Furthermore, the glycotransferase GALNT1 was highly expressed in BCMab1(+)CD44(+) cells and correlated with clinicopathologic features of bladder cancers. 26676748 1 80 theme bladder 241:247 arg1 initiation 255:264 bladder tumor initiation 241:264 bladder tumor initiation 241:264 The existence of bladder cancer stem cells (BCSC) has been suggested to underlie bladder tumor initiation and recurrence. 26531228 5 0 theme present 711:717 arg1 subunit 703:709 the O antigen subunit 689:709 the O antigen subunit present in the lipopolysaccharide of multiple R. solanacearum strains 689:779 Although multiple glycan forms were identified, the majority of the glycopeptides were modified with a pentasaccharide composed of HexNAc-(Pen)-dHex(3), similar to the O antigen subunit present in the lipopolysaccharide of multiple R. solanacearum strains. 26531228 10 1 theme solanacearum 1396:1407 arg1 pathogenesis 1377:1388 the pathogenesis 1373:1388 the pathogenesis of R. solanacearum 1373:1407 These results reveal the important role of glycosylation in the pathogenesis of R. solanacearum. 26531228 8 2 gly glycoprotein 1100:1111 arg1 glycoprotein 1100:1111 a single glycoprotein 1091:1111 a single glycoprotein 1091:1111 Only the levels of a single glycoprotein, the type IV pilin, were diminished in the absence of glycosylation. 26531228 8 2 gly glycoprotein 1100:1111 arg1 pilin 1126:1130 the type IV pilin 1114:1130 the type IV pilin 1114:1130 Only the levels of a single glycoprotein, the type IV pilin, were diminished in the absence of glycosylation. 26531228 6 3 theme glycosylation 841:853 arg1 loss 825:828 the total loss 815:828 the total loss of protein glycosylation 815:853 Disruption of the O-OTase led to the total loss of protein glycosylation, together with a defect in biofilm formation and reduced pathogenicity towards tomato plants. 26531228 6 4 dep together 856:863 arg1 with 865:868 with 865:868 with 865:868 Disruption of the O-OTase led to the total loss of protein glycosylation, together with a defect in biofilm formation and reduced pathogenicity towards tomato plants. 26531228 7 5 theme glycosylation 1006:1018 arg1 loss 998:1001 the loss 994:1001 the loss of glycosylation 994:1018 Comparative proteomic analysis revealed that the loss of glycosylation is not associated with widespread proteome changes. 26531228 5 6 mod modified 612:619 arg3 pentasaccharide 628:642 a pentasaccharide 626:642 a pentasaccharide composed of HexNAc-(Pen)-dHex(3), similar to the O antigen subunit present in the lipopolysaccharide of multiple R. solanacearum strains 626:779 Although multiple glycan forms were identified, the majority of the glycopeptides were modified with a pentasaccharide composed of HexNAc-(Pen)-dHex(3), similar to the O antigen subunit present in the lipopolysaccharide of multiple R. solanacearum strains. 26531228 5 6 mod modified 612:619 arg1 majority 577:584 the majority 573:584 the majority of the glycopeptides 573:605 Although multiple glycan forms were identified, the majority of the glycopeptides were modified with a pentasaccharide composed of HexNAc-(Pen)-dHex(3), similar to the O antigen subunit present in the lipopolysaccharide of multiple R. solanacearum strains. 26531228 6 7 theme total 819:823 arg1 loss 825:828 the total loss 815:828 the total loss of protein glycosylation 815:853 Disruption of the O-OTase led to the total loss of protein glycosylation, together with a defect in biofilm formation and reduced pathogenicity towards tomato plants. 26531228 3 8 theme responsible 327:337 arg1 O-oligosaccharyltransferase 289:315 the O-oligosaccharyltransferase 285:315 the O-oligosaccharyltransferase (O-OTase) responsible for protein O-glycosylation in R. solanacearum 285:384 In this work, we identified the O-oligosaccharyltransferase (O-OTase) responsible for protein O-glycosylation in R. solanacearum. 26531228 3 8 theme responsible 327:337 arg1 O-OTase 318:324 O-OTase 318:324 O-OTase 318:324 In this work, we identified the O-oligosaccharyltransferase (O-OTase) responsible for protein O-glycosylation in R. solanacearum. 26531228 5 9 from lipopolysaccharide 726:743 arg1 present 711:717 present 711:717 present 711:717 Although multiple glycan forms were identified, the majority of the glycopeptides were modified with a pentasaccharide composed of HexNAc-(Pen)-dHex(3), similar to the O antigen subunit present in the lipopolysaccharide of multiple R. solanacearum strains. 26531228 5 10 dep R. 757:758 arg1 solanacearum 760:771 R. solanacearum 757:771 multiple R. solanacearum strains 748:779 Although multiple glycan forms were identified, the majority of the glycopeptides were modified with a pentasaccharide composed of HexNAc-(Pen)-dHex(3), similar to the O antigen subunit present in the lipopolysaccharide of multiple R. solanacearum strains. 26531228 3 11 theme R. 370:371 arg1 solanacearum 373:384 R. solanacearum 370:384 R. solanacearum 370:384 In this work, we identified the O-oligosaccharyltransferase (O-OTase) responsible for protein O-glycosylation in R. solanacearum. 26531228 9 12 theme lectin 1272:1277 arg1 levels 1252:1257 the levels 1248:1257 the levels of a surface lectin homologous to Pseudomonas PA-IIL 1248:1310 In parallel, disruption of glycosylation triggered an increase in the levels of a surface lectin homologous to Pseudomonas PA-IIL. 26531228 4 13 theme type 457:460 arg1 pilins 465:470 type IV pilins 457:470 type IV pilins 457:470 An analysis of the glycoproteome revealed that 20 proteins, including type IV pilins are substrates of this general glycosylation system. 26531228 5 14 theme HexNAc- 656:662 arg1 -dHex 668:672 HexNAc-(Pen)-dHex(3) 656:675 HexNAc-(Pen)-dHex(3) 656:675 Although multiple glycan forms were identified, the majority of the glycopeptides were modified with a pentasaccharide composed of HexNAc-(Pen)-dHex(3), similar to the O antigen subunit present in the lipopolysaccharide of multiple R. solanacearum strains. 26531228 0 15 link O-linked 8:15 arg1 glycosylation 17:29 Protein O-linked glycosylation 0:29 Protein O-linked glycosylation 0:29 Protein O-linked glycosylation in the plant pathogen Ralstonia solanacearum. 26531228 6 16 theme tomato 934:939 arg1 plants 941:946 tomato plants 934:946 tomato plants 934:946 Disruption of the O-OTase led to the total loss of protein glycosylation, together with a defect in biofilm formation and reduced pathogenicity towards tomato plants. 26531228 3 17 from O-glycosylation 351:365 arg1 solanacearum 373:384 R. solanacearum 370:384 R. solanacearum 370:384 In this work, we identified the O-oligosaccharyltransferase (O-OTase) responsible for protein O-glycosylation in R. solanacearum. 26531228 9 18 from increase 1236:1243 arg1 levels 1252:1257 the levels 1248:1257 the levels of a surface lectin homologous to Pseudomonas PA-IIL 1248:1310 In parallel, disruption of glycosylation triggered an increase in the levels of a surface lectin homologous to Pseudomonas PA-IIL. 26531228 5 19 theme glycopeptides 593:605 arg1 majority 577:584 the majority 573:584 the majority of the glycopeptides 573:605 Although multiple glycan forms were identified, the majority of the glycopeptides were modified with a pentasaccharide composed of HexNAc-(Pen)-dHex(3), similar to the O antigen subunit present in the lipopolysaccharide of multiple R. solanacearum strains. 26531228 1 20 theme Ralstonia 77:85 arg1 solanacearum 87:98 Ralstonia solanacearum 77:98 Ralstonia solanacearum 77:98 Ralstonia solanacearum is one of the most lethal phytopathogens in the world. 26531228 5 21 theme O 693:693 arg1 subunit 703:709 the O antigen subunit 689:709 the O antigen subunit present in the lipopolysaccharide of multiple R. solanacearum strains 689:779 Although multiple glycan forms were identified, the majority of the glycopeptides were modified with a pentasaccharide composed of HexNAc-(Pen)-dHex(3), similar to the O antigen subunit present in the lipopolysaccharide of multiple R. solanacearum strains. 26531228 1 22 from phytopathogens 126:139 arg1 world 148:152 the world 144:152 the world 144:152 Ralstonia solanacearum is one of the most lethal phytopathogens in the world. 26531228 2 23 theme economic 238:245 arg1 interest 247:254 economic interest 238:254 economic interest 238:254 Due to its broad host range, it can cause wilting disease in many plant species of economic interest. 26531228 0 24 theme O-linked 8:15 arg1 glycosylation 17:29 Protein O-linked glycosylation 0:29 Protein O-linked glycosylation 0:29 Protein O-linked glycosylation in the plant pathogen Ralstonia solanacearum. 26531228 4 25 theme IV 462:463 arg1 pilins 465:470 type IV pilins 457:470 type IV pilins 457:470 An analysis of the glycoproteome revealed that 20 proteins, including type IV pilins are substrates of this general glycosylation system. 26531228 3 26 gly O-glycosylation 351:365 arg1 solanacearum 373:384 R. solanacearum 370:384 R. solanacearum 370:384 In this work, we identified the O-oligosaccharyltransferase (O-OTase) responsible for protein O-glycosylation in R. solanacearum. 26531228 8 27 theme single 1093:1098 arg1 glycoprotein 1100:1111 a single glycoprotein 1091:1111 a single glycoprotein 1091:1111 Only the levels of a single glycoprotein, the type IV pilin, were diminished in the absence of glycosylation. 26531228 8 27 theme single 1093:1098 arg1 pilin 1126:1130 the type IV pilin 1114:1130 the type IV pilin 1114:1130 Only the levels of a single glycoprotein, the type IV pilin, were diminished in the absence of glycosylation. 26531228 6 28 theme protein 833:839 arg1 glycosylation 841:853 protein glycosylation 833:853 protein glycosylation 833:853 Disruption of the O-OTase led to the total loss of protein glycosylation, together with a defect in biofilm formation and reduced pathogenicity towards tomato plants. 26531228 0 29 theme Protein 0:6 arg1 glycosylation 17:29 Protein O-linked glycosylation 0:29 Protein O-linked glycosylation 0:29 Protein O-linked glycosylation in the plant pathogen Ralstonia solanacearum. 26531228 7 30 theme proteomic 961:969 arg1 analysis 971:978 Comparative proteomic analysis 949:978 Comparative proteomic analysis 949:978 Comparative proteomic analysis revealed that the loss of glycosylation is not associated with widespread proteome changes. 26531228 7 31 theme proteome 1054:1061 arg1 changes 1063:1069 widespread proteome changes 1043:1069 widespread proteome changes 1043:1069 Comparative proteomic analysis revealed that the loss of glycosylation is not associated with widespread proteome changes. 26531228 10 32 theme glycosylation 1356:1368 arg1 role 1348:1351 the important role 1334:1351 the important role of glycosylation in the pathogenesis of R. solanacearum 1334:1407 These results reveal the important role of glycosylation in the pathogenesis of R. solanacearum. 26531228 6 33 theme O-OTase 800:806 arg1 Disruption 782:791 Disruption 782:791 Disruption of the O-OTase 782:806 Disruption of the O-OTase led to the total loss of protein glycosylation, together with a defect in biofilm formation and reduced pathogenicity towards tomato plants. 26531228 5 34 theme similar 678:684 arg1 -dHex 668:672 HexNAc-(Pen)-dHex(3) 656:675 HexNAc-(Pen)-dHex(3) 656:675 Although multiple glycan forms were identified, the majority of the glycopeptides were modified with a pentasaccharide composed of HexNAc-(Pen)-dHex(3), similar to the O antigen subunit present in the lipopolysaccharide of multiple R. solanacearum strains. 26531228 10 35 theme R. 1393:1394 arg1 solanacearum 1396:1407 R. solanacearum 1393:1407 R. solanacearum 1393:1407 These results reveal the important role of glycosylation in the pathogenesis of R. solanacearum. 26531228 3 36 theme protein 343:349 arg1 O-glycosylation 351:365 protein O-glycosylation 343:365 protein O-glycosylation in R. solanacearum 343:384 In this work, we identified the O-oligosaccharyltransferase (O-OTase) responsible for protein O-glycosylation in R. solanacearum. 26531228 9 37 theme homologous 1279:1288 arg1 lectin 1272:1277 a surface lectin 1262:1277 a surface lectin homologous to Pseudomonas PA-IIL 1262:1310 In parallel, disruption of glycosylation triggered an increase in the levels of a surface lectin homologous to Pseudomonas PA-IIL. 26531228 10 38 gly glycosylation 1356:1368 arg1 solanacearum 1396:1407 R. solanacearum 1393:1407 R. solanacearum 1393:1407 These results reveal the important role of glycosylation in the pathogenesis of R. solanacearum. 26531228 2 39 theme interest 247:254 arg1 species 227:233 many plant species 216:233 many plant species of economic interest 216:254 Due to its broad host range, it can cause wilting disease in many plant species of economic interest. 26531228 2 40 theme host 172:175 arg1 range 177:181 its broad host range 162:181 its broad host range 162:181 Due to its broad host range, it can cause wilting disease in many plant species of economic interest. 26531228 0 41 theme plant 38:42 arg1 solanacearum 63:74 the plant pathogen Ralstonia solanacearum 34:74 the plant pathogen Ralstonia solanacearum 34:74 Protein O-linked glycosylation in the plant pathogen Ralstonia solanacearum. 26531228 9 42 theme Pseudomonas 1293:1303 arg1 PA-IIL 1305:1310 Pseudomonas PA-IIL 1293:1310 Pseudomonas PA-IIL 1293:1310 In parallel, disruption of glycosylation triggered an increase in the levels of a surface lectin homologous to Pseudomonas PA-IIL. 26531228 2 43 theme broad 166:170 arg1 range 177:181 its broad host range 162:181 its broad host range 162:181 Due to its broad host range, it can cause wilting disease in many plant species of economic interest. 26531228 4 44 theme glycosylation 503:515 arg1 system 517:522 this general glycosylation system 490:522 this general glycosylation system 490:522 An analysis of the glycoproteome revealed that 20 proteins, including type IV pilins are substrates of this general glycosylation system. 26531228 8 45 theme glycoprotein 1100:1111 arg1 levels 1081:1086 Only the levels 1072:1086 Only the levels of a single glycoprotein, the type IV pilin, 1072:1131 Only the levels of a single glycoprotein, the type IV pilin, were diminished in the absence of glycosylation. 26531228 5 46 theme strains 773:779 arg1 lipopolysaccharide 726:743 the lipopolysaccharide 722:743 the lipopolysaccharide of multiple R. solanacearum strains 722:779 Although multiple glycan forms were identified, the majority of the glycopeptides were modified with a pentasaccharide composed of HexNAc-(Pen)-dHex(3), similar to the O antigen subunit present in the lipopolysaccharide of multiple R. solanacearum strains. 26531228 8 47 theme IV 1123:1124 arg1 glycoprotein 1100:1111 a single glycoprotein 1091:1111 a single glycoprotein 1091:1111 Only the levels of a single glycoprotein, the type IV pilin, were diminished in the absence of glycosylation. 26531228 8 47 theme IV 1123:1124 arg1 pilin 1126:1130 the type IV pilin 1114:1130 the type IV pilin 1114:1130 Only the levels of a single glycoprotein, the type IV pilin, were diminished in the absence of glycosylation. 26531228 0 48 theme Ralstonia 53:61 arg1 solanacearum 63:74 the plant pathogen Ralstonia solanacearum 34:74 the plant pathogen Ralstonia solanacearum 34:74 Protein O-linked glycosylation in the plant pathogen Ralstonia solanacearum. 26531228 4 49 theme general 495:501 arg1 system 517:522 this general glycosylation system 490:522 this general glycosylation system 490:522 An analysis of the glycoproteome revealed that 20 proteins, including type IV pilins are substrates of this general glycosylation system. 26531228 5 50 theme multiple 748:755 arg1 strains 773:779 multiple R. solanacearum strains 748:779 multiple R. solanacearum strains 748:779 Although multiple glycan forms were identified, the majority of the glycopeptides were modified with a pentasaccharide composed of HexNAc-(Pen)-dHex(3), similar to the O antigen subunit present in the lipopolysaccharide of multiple R. solanacearum strains. 26531228 7 51 theme widespread 1043:1052 arg1 changes 1063:1069 widespread proteome changes 1043:1069 widespread proteome changes 1043:1069 Comparative proteomic analysis revealed that the loss of glycosylation is not associated with widespread proteome changes. 26531228 2 52 theme wilting 197:203 arg1 disease 205:211 wilting disease 197:211 wilting disease 197:211 Due to its broad host range, it can cause wilting disease in many plant species of economic interest. 26531228 5 53 theme multiple 534:541 arg1 forms 550:554 multiple glycan forms 534:554 multiple glycan forms 534:554 Although multiple glycan forms were identified, the majority of the glycopeptides were modified with a pentasaccharide composed of HexNAc-(Pen)-dHex(3), similar to the O antigen subunit present in the lipopolysaccharide of multiple R. solanacearum strains. 26531228 0 54 theme pathogen 44:51 arg1 solanacearum 63:74 the plant pathogen Ralstonia solanacearum 34:74 the plant pathogen Ralstonia solanacearum 34:74 Protein O-linked glycosylation in the plant pathogen Ralstonia solanacearum. 26531228 10 55 theme important 1338:1346 arg1 role 1348:1351 the important role 1334:1351 the important role of glycosylation in the pathogenesis of R. solanacearum 1334:1407 These results reveal the important role of glycosylation in the pathogenesis of R. solanacearum. 26531228 5 56 theme Pen 664:666 arg1 -dHex 668:672 HexNAc-(Pen)-dHex(3) 656:675 HexNAc-(Pen)-dHex(3) 656:675 Although multiple glycan forms were identified, the majority of the glycopeptides were modified with a pentasaccharide composed of HexNAc-(Pen)-dHex(3), similar to the O antigen subunit present in the lipopolysaccharide of multiple R. solanacearum strains. 26531228 5 57 from present 711:717 arg1 lipopolysaccharide 726:743 the lipopolysaccharide 722:743 the lipopolysaccharide of multiple R. solanacearum strains 722:779 Although multiple glycan forms were identified, the majority of the glycopeptides were modified with a pentasaccharide composed of HexNAc-(Pen)-dHex(3), similar to the O antigen subunit present in the lipopolysaccharide of multiple R. solanacearum strains. 26531228 5 58 theme glycan 543:548 arg1 forms 550:554 multiple glycan forms 534:554 multiple glycan forms 534:554 Although multiple glycan forms were identified, the majority of the glycopeptides were modified with a pentasaccharide composed of HexNAc-(Pen)-dHex(3), similar to the O antigen subunit present in the lipopolysaccharide of multiple R. solanacearum strains. 26531228 1 59 theme lethal 119:124 arg1 phytopathogens 126:139 the most lethal phytopathogens 110:139 the most lethal phytopathogens in the world 110:152 Ralstonia solanacearum is one of the most lethal phytopathogens in the world. 26531228 4 60 theme system 517:522 arg1 substrates 476:485 substrates 476:485 substrates of this general glycosylation system 476:522 An analysis of the glycoproteome revealed that 20 proteins, including type IV pilins are substrates of this general glycosylation system. 26531228 4 60 theme system 517:522 arg1 pilins 465:470 type IV pilins 457:470 type IV pilins 457:470 An analysis of the glycoproteome revealed that 20 proteins, including type IV pilins are substrates of this general glycosylation system. 26531228 4 60 theme system 517:522 arg1 proteins 437:444 20 proteins 434:444 20 proteins 434:444 An analysis of the glycoproteome revealed that 20 proteins, including type IV pilins are substrates of this general glycosylation system. 26531228 5 61 attach present 711:717 arg2 subunit 703:709 the O antigen subunit 689:709 the O antigen subunit present in the lipopolysaccharide of multiple R. solanacearum strains 689:779 Although multiple glycan forms were identified, the majority of the glycopeptides were modified with a pentasaccharide composed of HexNAc-(Pen)-dHex(3), similar to the O antigen subunit present in the lipopolysaccharide of multiple R. solanacearum strains. 26531228 5 61 attach present 711:717 arg1 lipopolysaccharide 726:743 the lipopolysaccharide 722:743 the lipopolysaccharide of multiple R. solanacearum strains 722:779 Although multiple glycan forms were identified, the majority of the glycopeptides were modified with a pentasaccharide composed of HexNAc-(Pen)-dHex(3), similar to the O antigen subunit present in the lipopolysaccharide of multiple R. solanacearum strains. 26531228 1 62 theme phytopathogens 126:139 arg1 phytopathogens 126:139 the most lethal phytopathogens 110:139 the most lethal phytopathogens in the world 110:152 Ralstonia solanacearum is one of the most lethal phytopathogens in the world. 26531228 1 62 theme phytopathogens 126:139 arg1 one 103:105 one 103:105 one 103:105 Ralstonia solanacearum is one of the most lethal phytopathogens in the world. 26531228 8 63 theme type 1118:1121 arg1 glycoprotein 1100:1111 a single glycoprotein 1091:1111 a single glycoprotein 1091:1111 Only the levels of a single glycoprotein, the type IV pilin, were diminished in the absence of glycosylation. 26531228 8 63 theme type 1118:1121 arg1 pilin 1126:1130 the type IV pilin 1114:1130 the type IV pilin 1114:1130 Only the levels of a single glycoprotein, the type IV pilin, were diminished in the absence of glycosylation. 26531228 9 64 theme glycosylation 1209:1221 arg1 disruption 1195:1204 disruption 1195:1204 disruption of glycosylation 1195:1221 In parallel, disruption of glycosylation triggered an increase in the levels of a surface lectin homologous to Pseudomonas PA-IIL. 26531228 0 65 dep glycosylation 17:29 arg1 solanacearum 63:74 the plant pathogen Ralstonia solanacearum 34:74 the plant pathogen Ralstonia solanacearum 34:74 Protein O-linked glycosylation in the plant pathogen Ralstonia solanacearum. 26531228 9 66 theme surface 1264:1270 arg1 lectin 1272:1277 a surface lectin 1262:1277 a surface lectin homologous to Pseudomonas PA-IIL 1262:1310 In parallel, disruption of glycosylation triggered an increase in the levels of a surface lectin homologous to Pseudomonas PA-IIL. 26531228 10 67 from role 1348:1351 arg1 pathogenesis 1377:1388 the pathogenesis 1373:1388 the pathogenesis of R. solanacearum 1373:1407 These results reveal the important role of glycosylation in the pathogenesis of R. solanacearum. 26531228 5 68 theme antigen 695:701 arg1 subunit 703:709 the O antigen subunit 689:709 the O antigen subunit present in the lipopolysaccharide of multiple R. solanacearum strains 689:779 Although multiple glycan forms were identified, the majority of the glycopeptides were modified with a pentasaccharide composed of HexNAc-(Pen)-dHex(3), similar to the O antigen subunit present in the lipopolysaccharide of multiple R. solanacearum strains. 26531228 4 69 theme glycoproteome 406:418 arg1 analysis 390:397 An analysis 387:397 An analysis of the glycoproteome 387:418 An analysis of the glycoproteome revealed that 20 proteins, including type IV pilins are substrates of this general glycosylation system. 26531228 2 70 theme plant 221:225 arg1 species 227:233 many plant species 216:233 many plant species of economic interest 216:254 Due to its broad host range, it can cause wilting disease in many plant species of economic interest. 26531228 7 71 theme Comparative 949:959 arg1 analysis 971:978 Comparative proteomic analysis 949:978 Comparative proteomic analysis 949:978 Comparative proteomic analysis revealed that the loss of glycosylation is not associated with widespread proteome changes. 26531228 5 72 gly glycopeptides 593:605 arg2 glycopeptides 593:605 the glycopeptides 589:605 the glycopeptides 589:605 Although multiple glycan forms were identified, the majority of the glycopeptides were modified with a pentasaccharide composed of HexNAc-(Pen)-dHex(3), similar to the O antigen subunit present in the lipopolysaccharide of multiple R. solanacearum strains. 26531228 8 73 theme glycosylation 1167:1179 arg1 absence 1156:1162 the absence 1152:1162 the absence of glycosylation 1152:1179 Only the levels of a single glycoprotein, the type IV pilin, were diminished in the absence of glycosylation. 26531228 6 74 from defect 872:877 arg1 formation 890:898 biofilm formation 882:898 biofilm formation 882:898 Disruption of the O-OTase led to the total loss of protein glycosylation, together with a defect in biofilm formation and reduced pathogenicity towards tomato plants. 26531228 2 75 theme many 216:219 arg1 species 227:233 many plant species 216:233 many plant species of economic interest 216:254 Due to its broad host range, it can cause wilting disease in many plant species of economic interest. 26531228 5 76 theme R. 757:758 arg1 strains 773:779 multiple R. solanacearum strains 748:779 multiple R. solanacearum strains 748:779 Although multiple glycan forms were identified, the majority of the glycopeptides were modified with a pentasaccharide composed of HexNAc-(Pen)-dHex(3), similar to the O antigen subunit present in the lipopolysaccharide of multiple R. solanacearum strains. 26531228 6 77 theme biofilm 882:888 arg1 formation 890:898 biofilm formation 882:898 biofilm formation 882:898 Disruption of the O-OTase led to the total loss of protein glycosylation, together with a defect in biofilm formation and reduced pathogenicity towards tomato plants. 26492132 6 0 theme subcellular 1350:1360 arg1 localization 1362:1373 subcellular localization 1350:1373 subcellular localization 1350:1373 Thus, these results suggest that specific PTMs might play a role in switching dehydrin function or activity, water binding ability, protein-membrane interactions, transport and subcellular localization, interactions with targeted molecules, and protein stability. 26492132 3 1 theme dehydrin/response 537:553 arg1 protein 559:565 dehydrin/response ABA protein 537:565 dehydrin/response ABA protein migrating as a 26-kDa protein 537:595 These results suggest that the 44-kDa dehydrin protein is a putative dimer of dehydrin/response ABA protein migrating as a 26-kDa protein. 26492132 4 2 theme native 673:678 arg1 conditions 680:689 native conditions 673:689 native conditions 673:689 Dehydrins and dehydrin-like proteins form large oligomeric complexes under native conditions and are shown as several spots differing in pI through isoelectrofocusing analyses. 26492132 10 3 theme protein 1844:1850 arg1 structure 1852:1860 the protein structure 1840:1860 the protein structure 1840:1860 The lack of a fixed structure and exposition of amino acids on the surface of the protein structure enhances the accessibility to 40 predicted PTM sites, thereby facilitating dehydrin multifunctionality, which is discussed in the present study. 26492132 1 4 theme ABA 174:176 arg1 transcripts 178:188 dehydrin/response ABA transcripts 156:188 dehydrin/response ABA transcripts expression 156:199 A strong increase in the level of dehydrin/response ABA transcripts expression reported from the 14th week after flowering coincident with the accumulation of 26 and 44 kDa dehydrins in the embryonic axes of developing beech (Fagus sylvatica L.) seeds. 26492132 7 5 theme disulfide 1487:1495 arg1 bond 1497:1500 a disulfide bond 1485:1500 a disulfide bond 1485:1500 Despite the ability of two Cys residues to form a disulfide bond, -SH groups are likely not involved in dimer arrangement. 26492132 1 6 theme expression 190:199 arg1 level 147:151 the level 143:151 the level of dehydrin/response ABA transcripts expression 143:199 A strong increase in the level of dehydrin/response ABA transcripts expression reported from the 14th week after flowering coincident with the accumulation of 26 and 44 kDa dehydrins in the embryonic axes of developing beech (Fagus sylvatica L.) seeds. 26492132 7 7 theme Cys 1464:1466 arg1 residues 1468:1475 two Cys residues 1460:1475 two Cys residues 1460:1475 Despite the ability of two Cys residues to form a disulfide bond, -SH groups are likely not involved in dimer arrangement. 26492132 4 8 theme large 640:644 arg1 complexes 657:665 large oligomeric complexes 640:665 large oligomeric complexes 640:665 Dehydrins and dehydrin-like proteins form large oligomeric complexes under native conditions and are shown as several spots differing in pI through isoelectrofocusing analyses. 26492132 3 9 theme protein 559:565 arg1 protein 506:512 the 44-kDa dehydrin protein 486:512 the 44-kDa dehydrin protein 486:512 These results suggest that the 44-kDa dehydrin protein is a putative dimer of dehydrin/response ABA protein migrating as a 26-kDa protein. 26492132 3 9 theme protein 559:565 arg1 dimer 528:532 a putative dimer 517:532 a putative dimer of dehydrin/response ABA protein migrating as a 26-kDa protein 517:595 These results suggest that the 44-kDa dehydrin protein is a putative dimer of dehydrin/response ABA protein migrating as a 26-kDa protein. 26492132 6 10 theme protein-membrane 1305:1320 arg1 interactions 1322:1333 protein-membrane interactions 1305:1333 protein-membrane interactions 1305:1333 Thus, these results suggest that specific PTMs might play a role in switching dehydrin function or activity, water binding ability, protein-membrane interactions, transport and subcellular localization, interactions with targeted molecules, and protein stability. 26492132 5 11 theme dehydrin/response 883:899 arg1 sequence 913:920 the dehydrin/response ABA protein sequence 879:920 the dehydrin/response ABA protein sequence 879:920 Detailed prediction of specific sites accessible for various post-translational modifications (PTMs) in the dehydrin/response ABA protein sequence revealed sites specific to acetylation, amidation, glycosylation, methylation, myristoylation, nitrosylation, O-linked β-N-acetylglucosamination and Yin-O-Yang modification, palmitoylation, phosphorylation, sumoylation, sulfation, and ubiquitination. 26492132 3 12 theme 26-kDa 582:587 arg1 protein 589:595 a 26-kDa protein 580:595 a 26-kDa protein 580:595 These results suggest that the 44-kDa dehydrin protein is a putative dimer of dehydrin/response ABA protein migrating as a 26-kDa protein. 26492132 6 13 theme water 1282:1286 arg1 ability 1296:1302 water binding ability 1282:1302 water binding ability 1282:1302 Thus, these results suggest that specific PTMs might play a role in switching dehydrin function or activity, water binding ability, protein-membrane interactions, transport and subcellular localization, interactions with targeted molecules, and protein stability. 26492132 0 14 theme sylvatica 61:69 arg1 seeds 71:75 Fagus sylvatica seeds 55:75 Fagus sylvatica seeds using experimental and in silico approaches 55:119 Functional characterization of a dehydrin protein from Fagus sylvatica seeds using experimental and in silico approaches. 26492132 5 15 theme accessible 813:822 arg1 sites 807:811 specific sites 798:811 specific sites accessible for various post-translational modifications (PTMs) in the dehydrin/response ABA protein sequence 798:920 Detailed prediction of specific sites accessible for various post-translational modifications (PTMs) in the dehydrin/response ABA protein sequence revealed sites specific to acetylation, amidation, glycosylation, methylation, myristoylation, nitrosylation, O-linked β-N-acetylglucosamination and Yin-O-Yang modification, palmitoylation, phosphorylation, sumoylation, sulfation, and ubiquitination. 26492132 5 16 theme specific 937:944 arg1 sites 931:935 sites 931:935 sites specific to acetylation, amidation, glycosylation, methylation, myristoylation, nitrosylation, O-linked β-N-acetylglucosamination and Yin-O-Yang modification, palmitoylation, phosphorylation, sumoylation, sulfation, and ubiquitination 931:1170 Detailed prediction of specific sites accessible for various post-translational modifications (PTMs) in the dehydrin/response ABA protein sequence revealed sites specific to acetylation, amidation, glycosylation, methylation, myristoylation, nitrosylation, O-linked β-N-acetylglucosamination and Yin-O-Yang modification, palmitoylation, phosphorylation, sumoylation, sulfation, and ubiquitination. 26492132 4 17 theme several 708:714 arg1 Dehydrins 598:606 Dehydrins 598:606 Dehydrins 598:606 Dehydrins and dehydrin-like proteins form large oligomeric complexes under native conditions and are shown as several spots differing in pI through isoelectrofocusing analyses. 26492132 4 17 theme several 708:714 arg1 spots 716:720 several spots 708:720 several spots differing in pI through isoelectrofocusing analyses 708:772 Dehydrins and dehydrin-like proteins form large oligomeric complexes under native conditions and are shown as several spots differing in pI through isoelectrofocusing analyses. 26492132 5 18 theme specific 798:805 arg1 sites 807:811 specific sites 798:811 specific sites accessible for various post-translational modifications (PTMs) in the dehydrin/response ABA protein sequence 798:920 Detailed prediction of specific sites accessible for various post-translational modifications (PTMs) in the dehydrin/response ABA protein sequence revealed sites specific to acetylation, amidation, glycosylation, methylation, myristoylation, nitrosylation, O-linked β-N-acetylglucosamination and Yin-O-Yang modification, palmitoylation, phosphorylation, sumoylation, sulfation, and ubiquitination. 26492132 1 19 theme beech 341:345 arg1 seeds 368:372 beech (Fagus sylvatica L.) seeds 341:372 beech (Fagus sylvatica L.) seeds 341:372 A strong increase in the level of dehydrin/response ABA transcripts expression reported from the 14th week after flowering coincident with the accumulation of 26 and 44 kDa dehydrins in the embryonic axes of developing beech (Fagus sylvatica L.) seeds. 26492132 1 19 theme beech 341:345 arg1 Fagus 348:352 Fagus 348:352 Fagus 348:352 A strong increase in the level of dehydrin/response ABA transcripts expression reported from the 14th week after flowering coincident with the accumulation of 26 and 44 kDa dehydrins in the embryonic axes of developing beech (Fagus sylvatica L.) seeds. 26492132 8 20 theme potential 1601:1609 arg1 polyQ-tracts 1584:1595 polyQ-tracts 1584:1595 polyQ-tracts 1584:1595 His-rich regions and/or polyQ-tracts are potential candidates as spatial organization modulators. 26492132 8 20 theme potential 1601:1609 arg1 candidates 1611:1620 potential candidates 1601:1620 potential candidates as spatial organization modulators 1601:1655 His-rich regions and/or polyQ-tracts are potential candidates as spatial organization modulators. 26492132 8 20 theme potential 1601:1609 arg1 regions 1569:1575 His-rich regions 1560:1575 His-rich regions 1560:1575 His-rich regions and/or polyQ-tracts are potential candidates as spatial organization modulators. 26492132 0 21 theme protein 42:48 arg1 characterization 11:26 Functional characterization 0:26 Functional characterization of a dehydrin protein from Fagus sylvatica seeds using experimental and in silico approaches. 0:120 Functional characterization of a dehydrin protein from Fagus sylvatica seeds using experimental and in silico approaches. 26492132 9 22 theme Dehydrin/response 1658:1674 arg1 protein 1719:1725 an intrinsically disordered protein 1691:1725 an intrinsically disordered protein containing low complexity regions 1691:1759 Dehydrin/response ABA protein is an intrinsically disordered protein containing low complexity regions. 26492132 9 22 theme Dehydrin/response 1658:1674 arg1 protein 1680:1686 Dehydrin/response ABA protein 1658:1686 Dehydrin/response ABA protein 1658:1686 Dehydrin/response ABA protein is an intrinsically disordered protein containing low complexity regions. 26492132 2 23 theme maturation 440:449 arg1 drying 451:456 maturation drying 440:456 maturation drying 440:456 Both transcript and protein levels were strongly correlated with maturation drying. 26492132 4 24 theme isoelectrofocusing 746:763 arg1 analyses 765:772 isoelectrofocusing analyses 746:772 isoelectrofocusing analyses 746:772 Dehydrins and dehydrin-like proteins form large oligomeric complexes under native conditions and are shown as several spots differing in pI through isoelectrofocusing analyses. 26492132 0 25 theme Functional 0:9 arg1 characterization 11:26 Functional characterization 0:26 Functional characterization of a dehydrin protein from Fagus sylvatica seeds using experimental and in silico approaches. 0:120 Functional characterization of a dehydrin protein from Fagus sylvatica seeds using experimental and in silico approaches. 26492132 8 26 theme organization 1633:1644 arg1 modulators 1646:1655 spatial organization modulators 1625:1655 spatial organization modulators 1625:1655 His-rich regions and/or polyQ-tracts are potential candidates as spatial organization modulators. 26492132 10 27 theme exposition 1796:1805 arg1 lack 1766:1769 The lack 1762:1769 The lack of a fixed structure and exposition of amino acids on the surface of the protein structure 1762:1860 The lack of a fixed structure and exposition of amino acids on the surface of the protein structure enhances the accessibility to 40 predicted PTM sites, thereby facilitating dehydrin multifunctionality, which is discussed in the present study. 26492132 10 28 theme structure 1852:1860 arg1 surface 1829:1835 the surface 1825:1835 the surface of the protein structure 1825:1860 The lack of a fixed structure and exposition of amino acids on the surface of the protein structure enhances the accessibility to 40 predicted PTM sites, thereby facilitating dehydrin multifunctionality, which is discussed in the present study. 26492132 10 29 theme structure 1782:1790 arg1 lack 1766:1769 The lack 1762:1769 The lack of a fixed structure and exposition of amino acids on the surface of the protein structure 1762:1860 The lack of a fixed structure and exposition of amino acids on the surface of the protein structure enhances the accessibility to 40 predicted PTM sites, thereby facilitating dehydrin multifunctionality, which is discussed in the present study. 26492132 2 30 theme protein 395:401 arg1 levels 403:408 protein levels 395:408 protein levels 395:408 Both transcript and protein levels were strongly correlated with maturation drying. 26492132 1 31 theme dehydrin/response 156:172 arg1 transcripts 178:188 dehydrin/response ABA transcripts 156:188 dehydrin/response ABA transcripts expression 156:199 A strong increase in the level of dehydrin/response ABA transcripts expression reported from the 14th week after flowering coincident with the accumulation of 26 and 44 kDa dehydrins in the embryonic axes of developing beech (Fagus sylvatica L.) seeds. 26492132 0 32 theme dehydrin 33:40 arg1 protein 42:48 a dehydrin protein 31:48 a dehydrin protein 31:48 Functional characterization of a dehydrin protein from Fagus sylvatica seeds using experimental and in silico approaches. 26492132 9 33 theme disordered 1708:1717 arg1 protein 1719:1725 an intrinsically disordered protein 1691:1725 an intrinsically disordered protein containing low complexity regions 1691:1759 Dehydrin/response ABA protein is an intrinsically disordered protein containing low complexity regions. 26492132 9 33 theme disordered 1708:1717 arg1 protein 1680:1686 Dehydrin/response ABA protein 1658:1686 Dehydrin/response ABA protein 1658:1686 Dehydrin/response ABA protein is an intrinsically disordered protein containing low complexity regions. 26492132 10 34 from lack 1766:1769 arg1 surface 1829:1835 the surface 1825:1835 the surface of the protein structure 1825:1860 The lack of a fixed structure and exposition of amino acids on the surface of the protein structure enhances the accessibility to 40 predicted PTM sites, thereby facilitating dehydrin multifunctionality, which is discussed in the present study. 26492132 5 35 theme various 828:834 arg1 modifications 855:867 various post-translational modifications 828:867 various post-translational modifications (PTMs) in the dehydrin/response ABA protein sequence 828:920 Detailed prediction of specific sites accessible for various post-translational modifications (PTMs) in the dehydrin/response ABA protein sequence revealed sites specific to acetylation, amidation, glycosylation, methylation, myristoylation, nitrosylation, O-linked β-N-acetylglucosamination and Yin-O-Yang modification, palmitoylation, phosphorylation, sumoylation, sulfation, and ubiquitination. 26492132 5 35 theme various 828:834 arg1 PTMs 870:873 PTMs 870:873 PTMs 870:873 Detailed prediction of specific sites accessible for various post-translational modifications (PTMs) in the dehydrin/response ABA protein sequence revealed sites specific to acetylation, amidation, glycosylation, methylation, myristoylation, nitrosylation, O-linked β-N-acetylglucosamination and Yin-O-Yang modification, palmitoylation, phosphorylation, sumoylation, sulfation, and ubiquitination. 26492132 1 36 theme embryonic 312:320 arg1 axes 322:325 the embryonic axes 308:325 the embryonic axes of developing beech (Fagus sylvatica L.) seeds 308:372 A strong increase in the level of dehydrin/response ABA transcripts expression reported from the 14th week after flowering coincident with the accumulation of 26 and 44 kDa dehydrins in the embryonic axes of developing beech (Fagus sylvatica L.) seeds. 26492132 6 37 theme specific 1206:1213 arg1 PTMs 1215:1218 specific PTMs 1206:1218 specific PTMs 1206:1218 Thus, these results suggest that specific PTMs might play a role in switching dehydrin function or activity, water binding ability, protein-membrane interactions, transport and subcellular localization, interactions with targeted molecules, and protein stability. 26492132 10 38 theme amino 1810:1814 arg1 acids 1816:1820 amino acids 1810:1820 amino acids 1810:1820 The lack of a fixed structure and exposition of amino acids on the surface of the protein structure enhances the accessibility to 40 predicted PTM sites, thereby facilitating dehydrin multifunctionality, which is discussed in the present study. 26492132 9 39 theme complexity 1742:1751 arg1 regions 1753:1759 low complexity regions 1738:1759 low complexity regions 1738:1759 Dehydrin/response ABA protein is an intrinsically disordered protein containing low complexity regions. 26492132 5 40 theme protein 905:911 arg1 sequence 913:920 the dehydrin/response ABA protein sequence 879:920 the dehydrin/response ABA protein sequence 879:920 Detailed prediction of specific sites accessible for various post-translational modifications (PTMs) in the dehydrin/response ABA protein sequence revealed sites specific to acetylation, amidation, glycosylation, methylation, myristoylation, nitrosylation, O-linked β-N-acetylglucosamination and Yin-O-Yang modification, palmitoylation, phosphorylation, sumoylation, sulfation, and ubiquitination. 26492132 4 41 theme dehydrin-like 612:624 arg1 proteins 626:633 dehydrin-like proteins 612:633 dehydrin-like proteins 612:633 Dehydrins and dehydrin-like proteins form large oligomeric complexes under native conditions and are shown as several spots differing in pI through isoelectrofocusing analyses. 26492132 3 42 theme dehydrin 497:504 arg1 protein 506:512 the 44-kDa dehydrin protein 486:512 the 44-kDa dehydrin protein 486:512 These results suggest that the 44-kDa dehydrin protein is a putative dimer of dehydrin/response ABA protein migrating as a 26-kDa protein. 26492132 3 42 theme dehydrin 497:504 arg1 dimer 528:532 a putative dimer 517:532 a putative dimer of dehydrin/response ABA protein migrating as a 26-kDa protein 517:595 These results suggest that the 44-kDa dehydrin protein is a putative dimer of dehydrin/response ABA protein migrating as a 26-kDa protein. 26492132 6 43 with interactions 1322:1333 arg1 molecules 1403:1411 targeted molecules 1394:1411 targeted molecules 1394:1411 Thus, these results suggest that specific PTMs might play a role in switching dehydrin function or activity, water binding ability, protein-membrane interactions, transport and subcellular localization, interactions with targeted molecules, and protein stability. 26492132 7 44 theme dimer 1541:1545 arg1 arrangement 1547:1557 dimer arrangement 1541:1557 dimer arrangement 1541:1557 Despite the ability of two Cys residues to form a disulfide bond, -SH groups are likely not involved in dimer arrangement. 26492132 6 45 with transport 1336:1344 arg1 molecules 1403:1411 targeted molecules 1394:1411 targeted molecules 1394:1411 Thus, these results suggest that specific PTMs might play a role in switching dehydrin function or activity, water binding ability, protein-membrane interactions, transport and subcellular localization, interactions with targeted molecules, and protein stability. 26492132 5 46 link O-linked 1032:1039 arg1 β-N-acetylglucosamination 1041:1065 O-linked β-N-acetylglucosamination 1032:1065 O-linked β-N-acetylglucosamination 1032:1065 Detailed prediction of specific sites accessible for various post-translational modifications (PTMs) in the dehydrin/response ABA protein sequence revealed sites specific to acetylation, amidation, glycosylation, methylation, myristoylation, nitrosylation, O-linked β-N-acetylglucosamination and Yin-O-Yang modification, palmitoylation, phosphorylation, sumoylation, sulfation, and ubiquitination. 26492132 6 47 theme dehydrin 1251:1258 arg1 function 1260:1267 dehydrin function 1251:1267 dehydrin function 1251:1267 Thus, these results suggest that specific PTMs might play a role in switching dehydrin function or activity, water binding ability, protein-membrane interactions, transport and subcellular localization, interactions with targeted molecules, and protein stability. 26492132 3 48 theme putative 519:526 arg1 protein 506:512 the 44-kDa dehydrin protein 486:512 the 44-kDa dehydrin protein 486:512 These results suggest that the 44-kDa dehydrin protein is a putative dimer of dehydrin/response ABA protein migrating as a 26-kDa protein. 26492132 3 48 theme putative 519:526 arg1 dimer 528:532 a putative dimer 517:532 a putative dimer of dehydrin/response ABA protein migrating as a 26-kDa protein 517:595 These results suggest that the 44-kDa dehydrin protein is a putative dimer of dehydrin/response ABA protein migrating as a 26-kDa protein. 26492132 5 49 theme ABA 901:903 arg1 sequence 913:920 the dehydrin/response ABA protein sequence 879:920 the dehydrin/response ABA protein sequence 879:920 Detailed prediction of specific sites accessible for various post-translational modifications (PTMs) in the dehydrin/response ABA protein sequence revealed sites specific to acetylation, amidation, glycosylation, methylation, myristoylation, nitrosylation, O-linked β-N-acetylglucosamination and Yin-O-Yang modification, palmitoylation, phosphorylation, sumoylation, sulfation, and ubiquitination. 26492132 7 50 theme -SH 1503:1505 arg1 groups 1507:1512 -SH groups 1503:1512 -SH groups 1503:1512 Despite the ability of two Cys residues to form a disulfide bond, -SH groups are likely not involved in dimer arrangement. 26492132 9 51 contain containing 1727:1736 arg1 protein 1719:1725 an intrinsically disordered protein 1691:1725 an intrinsically disordered protein containing low complexity regions 1691:1759 Dehydrin/response ABA protein is an intrinsically disordered protein containing low complexity regions. 26492132 9 51 contain containing 1727:1736 arg1 protein 1680:1686 Dehydrin/response ABA protein 1658:1686 Dehydrin/response ABA protein 1658:1686 Dehydrin/response ABA protein is an intrinsically disordered protein containing low complexity regions. 26492132 9 51 contain containing 1727:1736 arg2 regions 1753:1759 low complexity regions 1738:1759 low complexity regions 1738:1759 Dehydrin/response ABA protein is an intrinsically disordered protein containing low complexity regions. 26492132 10 52 theme predicted 1895:1903 arg1 sites 1909:1913 40 predicted PTM sites 1892:1913 40 predicted PTM sites 1892:1913 The lack of a fixed structure and exposition of amino acids on the surface of the protein structure enhances the accessibility to 40 predicted PTM sites, thereby facilitating dehydrin multifunctionality, which is discussed in the present study. 26492132 6 53 with stability 1426:1434 arg1 molecules 1403:1411 targeted molecules 1394:1411 targeted molecules 1394:1411 Thus, these results suggest that specific PTMs might play a role in switching dehydrin function or activity, water binding ability, protein-membrane interactions, transport and subcellular localization, interactions with targeted molecules, and protein stability. 26492132 1 54 theme transcripts 178:188 arg1 expression 190:199 dehydrin/response ABA transcripts expression 156:199 dehydrin/response ABA transcripts expression 156:199 A strong increase in the level of dehydrin/response ABA transcripts expression reported from the 14th week after flowering coincident with the accumulation of 26 and 44 kDa dehydrins in the embryonic axes of developing beech (Fagus sylvatica L.) seeds. 26492132 1 55 from accumulation 265:276 arg1 axes 322:325 the embryonic axes 308:325 the embryonic axes of developing beech (Fagus sylvatica L.) seeds 308:372 A strong increase in the level of dehydrin/response ABA transcripts expression reported from the 14th week after flowering coincident with the accumulation of 26 and 44 kDa dehydrins in the embryonic axes of developing beech (Fagus sylvatica L.) seeds. 26492132 3 56 theme ABA 555:557 arg1 protein 559:565 dehydrin/response ABA protein 537:565 dehydrin/response ABA protein migrating as a 26-kDa protein 537:595 These results suggest that the 44-kDa dehydrin protein is a putative dimer of dehydrin/response ABA protein migrating as a 26-kDa protein. 26492132 6 57 with function 1260:1267 arg1 molecules 1403:1411 targeted molecules 1394:1411 targeted molecules 1394:1411 Thus, these results suggest that specific PTMs might play a role in switching dehydrin function or activity, water binding ability, protein-membrane interactions, transport and subcellular localization, interactions with targeted molecules, and protein stability. 26492132 10 58 theme acids 1816:1820 arg1 structure 1782:1790 a fixed structure 1774:1790 a fixed structure 1774:1790 The lack of a fixed structure and exposition of amino acids on the surface of the protein structure enhances the accessibility to 40 predicted PTM sites, thereby facilitating dehydrin multifunctionality, which is discussed in the present study. 26492132 10 58 theme acids 1816:1820 arg1 exposition 1796:1805 exposition 1796:1805 exposition 1796:1805 The lack of a fixed structure and exposition of amino acids on the surface of the protein structure enhances the accessibility to 40 predicted PTM sites, thereby facilitating dehydrin multifunctionality, which is discussed in the present study. 26492132 6 59 theme protein 1418:1424 arg1 stability 1426:1434 protein stability 1418:1434 protein stability 1418:1434 Thus, these results suggest that specific PTMs might play a role in switching dehydrin function or activity, water binding ability, protein-membrane interactions, transport and subcellular localization, interactions with targeted molecules, and protein stability. 26492132 0 60 from seeds 71:75 arg1 characterization 11:26 Functional characterization 0:26 Functional characterization of a dehydrin protein from Fagus sylvatica seeds using experimental and in silico approaches. 0:120 Functional characterization of a dehydrin protein from Fagus sylvatica seeds using experimental and in silico approaches. 26492132 4 61 theme oligomeric 646:655 arg1 complexes 657:665 large oligomeric complexes 640:665 large oligomeric complexes 640:665 Dehydrins and dehydrin-like proteins form large oligomeric complexes under native conditions and are shown as several spots differing in pI through isoelectrofocusing analyses. 26492132 6 62 theme binding 1288:1294 arg1 ability 1296:1302 water binding ability 1282:1302 water binding ability 1282:1302 Thus, these results suggest that specific PTMs might play a role in switching dehydrin function or activity, water binding ability, protein-membrane interactions, transport and subcellular localization, interactions with targeted molecules, and protein stability. 26492132 6 63 theme targeted 1394:1401 arg1 molecules 1403:1411 targeted molecules 1394:1411 targeted molecules 1394:1411 Thus, these results suggest that specific PTMs might play a role in switching dehydrin function or activity, water binding ability, protein-membrane interactions, transport and subcellular localization, interactions with targeted molecules, and protein stability. 26492132 1 64 theme strong 124:129 arg1 increase 131:138 A strong increase 122:138 A strong increase in the level of dehydrin/response ABA transcripts expression 122:199 A strong increase in the level of dehydrin/response ABA transcripts expression reported from the 14th week after flowering coincident with the accumulation of 26 and 44 kDa dehydrins in the embryonic axes of developing beech (Fagus sylvatica L.) seeds. 26492132 6 65 with ability 1296:1302 arg1 molecules 1403:1411 targeted molecules 1394:1411 targeted molecules 1394:1411 Thus, these results suggest that specific PTMs might play a role in switching dehydrin function or activity, water binding ability, protein-membrane interactions, transport and subcellular localization, interactions with targeted molecules, and protein stability. 26492132 8 66 theme His-rich 1560:1567 arg1 polyQ-tracts 1584:1595 polyQ-tracts 1584:1595 polyQ-tracts 1584:1595 His-rich regions and/or polyQ-tracts are potential candidates as spatial organization modulators. 26492132 8 66 theme His-rich 1560:1567 arg1 candidates 1611:1620 potential candidates 1601:1620 potential candidates as spatial organization modulators 1601:1655 His-rich regions and/or polyQ-tracts are potential candidates as spatial organization modulators. 26492132 8 66 theme His-rich 1560:1567 arg1 regions 1569:1575 His-rich regions 1560:1575 His-rich regions 1560:1575 His-rich regions and/or polyQ-tracts are potential candidates as spatial organization modulators. 26492132 5 67 theme Detailed 775:782 arg1 prediction 784:793 Detailed prediction 775:793 Detailed prediction of specific sites accessible for various post-translational modifications (PTMs) in the dehydrin/response ABA protein sequence 775:920 Detailed prediction of specific sites accessible for various post-translational modifications (PTMs) in the dehydrin/response ABA protein sequence revealed sites specific to acetylation, amidation, glycosylation, methylation, myristoylation, nitrosylation, O-linked β-N-acetylglucosamination and Yin-O-Yang modification, palmitoylation, phosphorylation, sumoylation, sulfation, and ubiquitination. 26492132 10 68 theme dehydrin 1937:1944 arg1 multifunctionality 1946:1963 dehydrin multifunctionality 1937:1963 dehydrin multifunctionality 1937:1963 The lack of a fixed structure and exposition of amino acids on the surface of the protein structure enhances the accessibility to 40 predicted PTM sites, thereby facilitating dehydrin multifunctionality, which is discussed in the present study. 26492132 0 69 theme experimental 83:94 arg1 approaches 110:119 experimental and in silico approaches 83:119 experimental and in silico approaches 83:119 Functional characterization of a dehydrin protein from Fagus sylvatica seeds using experimental and in silico approaches. 26492132 6 70 with activity 1272:1279 arg1 molecules 1403:1411 targeted molecules 1394:1411 targeted molecules 1394:1411 Thus, these results suggest that specific PTMs might play a role in switching dehydrin function or activity, water binding ability, protein-membrane interactions, transport and subcellular localization, interactions with targeted molecules, and protein stability. 26492132 0 71 theme in 100:101 arg1 approaches 110:119 experimental and in silico approaches 83:119 experimental and in silico approaches 83:119 Functional characterization of a dehydrin protein from Fagus sylvatica seeds using experimental and in silico approaches. 26492132 0 72 dep in 100:101 arg1 silico 103:108 silico 103:108 silico 103:108 Functional characterization of a dehydrin protein from Fagus sylvatica seeds using experimental and in silico approaches. 26492132 8 73 theme spatial 1625:1631 arg1 modulators 1646:1655 spatial organization modulators 1625:1655 spatial organization modulators 1625:1655 His-rich regions and/or polyQ-tracts are potential candidates as spatial organization modulators. 26492132 5 74 theme post-translational 836:853 arg1 modifications 855:867 various post-translational modifications 828:867 various post-translational modifications (PTMs) in the dehydrin/response ABA protein sequence 828:920 Detailed prediction of specific sites accessible for various post-translational modifications (PTMs) in the dehydrin/response ABA protein sequence revealed sites specific to acetylation, amidation, glycosylation, methylation, myristoylation, nitrosylation, O-linked β-N-acetylglucosamination and Yin-O-Yang modification, palmitoylation, phosphorylation, sumoylation, sulfation, and ubiquitination. 26492132 5 74 theme post-translational 836:853 arg1 PTMs 870:873 PTMs 870:873 PTMs 870:873 Detailed prediction of specific sites accessible for various post-translational modifications (PTMs) in the dehydrin/response ABA protein sequence revealed sites specific to acetylation, amidation, glycosylation, methylation, myristoylation, nitrosylation, O-linked β-N-acetylglucosamination and Yin-O-Yang modification, palmitoylation, phosphorylation, sumoylation, sulfation, and ubiquitination. 26492132 5 75 from modifications 855:867 arg1 sequence 913:920 the dehydrin/response ABA protein sequence 879:920 the dehydrin/response ABA protein sequence 879:920 Detailed prediction of specific sites accessible for various post-translational modifications (PTMs) in the dehydrin/response ABA protein sequence revealed sites specific to acetylation, amidation, glycosylation, methylation, myristoylation, nitrosylation, O-linked β-N-acetylglucosamination and Yin-O-Yang modification, palmitoylation, phosphorylation, sumoylation, sulfation, and ubiquitination. 26492132 1 76 from increase 131:138 arg1 level 147:151 the level 143:151 the level of dehydrin/response ABA transcripts expression 143:199 A strong increase in the level of dehydrin/response ABA transcripts expression reported from the 14th week after flowering coincident with the accumulation of 26 and 44 kDa dehydrins in the embryonic axes of developing beech (Fagus sylvatica L.) seeds. 26492132 9 77 theme ABA 1676:1678 arg1 protein 1719:1725 an intrinsically disordered protein 1691:1725 an intrinsically disordered protein containing low complexity regions 1691:1759 Dehydrin/response ABA protein is an intrinsically disordered protein containing low complexity regions. 26492132 9 77 theme ABA 1676:1678 arg1 protein 1680:1686 Dehydrin/response ABA protein 1658:1686 Dehydrin/response ABA protein 1658:1686 Dehydrin/response ABA protein is an intrinsically disordered protein containing low complexity regions. 26492132 7 78 theme residues 1468:1475 arg1 ability 1449:1455 the ability 1445:1455 the ability of two Cys residues to form a disulfide bond 1445:1500 Despite the ability of two Cys residues to form a disulfide bond, -SH groups are likely not involved in dimer arrangement. 26492132 5 79 theme sites 807:811 arg1 prediction 784:793 Detailed prediction 775:793 Detailed prediction of specific sites accessible for various post-translational modifications (PTMs) in the dehydrin/response ABA protein sequence 775:920 Detailed prediction of specific sites accessible for various post-translational modifications (PTMs) in the dehydrin/response ABA protein sequence revealed sites specific to acetylation, amidation, glycosylation, methylation, myristoylation, nitrosylation, O-linked β-N-acetylglucosamination and Yin-O-Yang modification, palmitoylation, phosphorylation, sumoylation, sulfation, and ubiquitination. 26492132 1 80 theme dehydrins 295:303 arg1 accumulation 265:276 the accumulation 261:276 the accumulation of 26 and 44 kDa dehydrins in the embryonic axes of developing beech (Fagus sylvatica L.) seeds 261:372 A strong increase in the level of dehydrin/response ABA transcripts expression reported from the 14th week after flowering coincident with the accumulation of 26 and 44 kDa dehydrins in the embryonic axes of developing beech (Fagus sylvatica L.) seeds. 26492132 10 81 theme PTM 1905:1907 arg1 sites 1909:1913 40 predicted PTM sites 1892:1913 40 predicted PTM sites 1892:1913 The lack of a fixed structure and exposition of amino acids on the surface of the protein structure enhances the accessibility to 40 predicted PTM sites, thereby facilitating dehydrin multifunctionality, which is discussed in the present study. 26492132 10 82 theme fixed 1776:1780 arg1 structure 1782:1790 a fixed structure 1774:1790 a fixed structure 1774:1790 The lack of a fixed structure and exposition of amino acids on the surface of the protein structure enhances the accessibility to 40 predicted PTM sites, thereby facilitating dehydrin multifunctionality, which is discussed in the present study. 26492132 0 83 theme Fagus 55:59 arg1 seeds 71:75 Fagus sylvatica seeds 55:75 Fagus sylvatica seeds using experimental and in silico approaches 55:119 Functional characterization of a dehydrin protein from Fagus sylvatica seeds using experimental and in silico approaches. 26492132 1 84 dep Fagus 348:352 arg1 L. 364:365 Fagus sylvatica L. 348:365 Fagus sylvatica L. 348:365 A strong increase in the level of dehydrin/response ABA transcripts expression reported from the 14th week after flowering coincident with the accumulation of 26 and 44 kDa dehydrins in the embryonic axes of developing beech (Fagus sylvatica L.) seeds. 26492132 3 85 theme 44-kDa 490:495 arg1 protein 506:512 the 44-kDa dehydrin protein 486:512 the 44-kDa dehydrin protein 486:512 These results suggest that the 44-kDa dehydrin protein is a putative dimer of dehydrin/response ABA protein migrating as a 26-kDa protein. 26492132 3 85 theme 44-kDa 490:495 arg1 dimer 528:532 a putative dimer 517:532 a putative dimer of dehydrin/response ABA protein migrating as a 26-kDa protein 517:595 These results suggest that the 44-kDa dehydrin protein is a putative dimer of dehydrin/response ABA protein migrating as a 26-kDa protein. 26492132 6 86 with localization 1362:1373 arg1 molecules 1403:1411 targeted molecules 1394:1411 targeted molecules 1394:1411 Thus, these results suggest that specific PTMs might play a role in switching dehydrin function or activity, water binding ability, protein-membrane interactions, transport and subcellular localization, interactions with targeted molecules, and protein stability. 26492132 9 87 theme low 1738:1740 arg1 regions 1753:1759 low complexity regions 1738:1759 low complexity regions 1738:1759 Dehydrin/response ABA protein is an intrinsically disordered protein containing low complexity regions. 26492132 5 88 theme O-linked 1032:1039 arg1 β-N-acetylglucosamination 1041:1065 O-linked β-N-acetylglucosamination 1032:1065 O-linked β-N-acetylglucosamination 1032:1065 Detailed prediction of specific sites accessible for various post-translational modifications (PTMs) in the dehydrin/response ABA protein sequence revealed sites specific to acetylation, amidation, glycosylation, methylation, myristoylation, nitrosylation, O-linked β-N-acetylglucosamination and Yin-O-Yang modification, palmitoylation, phosphorylation, sumoylation, sulfation, and ubiquitination. 26492132 10 89 theme present 1992:1998 arg1 study 2000:2004 the present study 1988:2004 the present study 1988:2004 The lack of a fixed structure and exposition of amino acids on the surface of the protein structure enhances the accessibility to 40 predicted PTM sites, thereby facilitating dehydrin multifunctionality, which is discussed in the present study. 26492132 6 90 with interactions 1376:1387 arg1 molecules 1403:1411 targeted molecules 1394:1411 targeted molecules 1394:1411 Thus, these results suggest that specific PTMs might play a role in switching dehydrin function or activity, water binding ability, protein-membrane interactions, transport and subcellular localization, interactions with targeted molecules, and protein stability. 26492132 5 91 theme Yin-O-Yang 1071:1080 arg1 modification 1082:1093 Yin-O-Yang modification 1071:1093 Yin-O-Yang modification 1071:1093 Detailed prediction of specific sites accessible for various post-translational modifications (PTMs) in the dehydrin/response ABA protein sequence revealed sites specific to acetylation, amidation, glycosylation, methylation, myristoylation, nitrosylation, O-linked β-N-acetylglucosamination and Yin-O-Yang modification, palmitoylation, phosphorylation, sumoylation, sulfation, and ubiquitination. 26492132 1 92 with coincident 245:254 arg1 accumulation 265:276 the accumulation 261:276 the accumulation of 26 and 44 kDa dehydrins in the embryonic axes of developing beech (Fagus sylvatica L.) seeds 261:372 A strong increase in the level of dehydrin/response ABA transcripts expression reported from the 14th week after flowering coincident with the accumulation of 26 and 44 kDa dehydrins in the embryonic axes of developing beech (Fagus sylvatica L.) seeds. 26492132 1 93 theme coincident 245:254 arg1 flowering 235:243 flowering 235:243 flowering coincident with the accumulation of 26 and 44 kDa dehydrins in the embryonic axes of developing beech (Fagus sylvatica L.) seeds 235:372 A strong increase in the level of dehydrin/response ABA transcripts expression reported from the 14th week after flowering coincident with the accumulation of 26 and 44 kDa dehydrins in the embryonic axes of developing beech (Fagus sylvatica L.) seeds. 27705803 3 0 theme high-density 305:316 arg1 network 338:344 Our high-density protein interaction network 301:344 Our high-density protein interaction network 301:344 Our high-density protein interaction network uncovered a diverse range of PcG complexes. 27705803 6 1 theme cellular 941:948 arg1 processes 950:958 cellular processes 941:958 cellular processes in mammals 941:969 Finally, genome-wide profiling of PR-DUB components indicated that the human PR-DUB and PRC1 complexes bind distinct sets of target genes, suggesting differential impact on cellular processes in mammals. 27705803 5 2 theme PR-DUB 634:639 arg1 complexes 658:666 two PR-DUB deubiquitination complexes 630:666 two PR-DUB deubiquitination complexes 630:666 We identified two human PRC2 complexes and two PR-DUB deubiquitination complexes, which contain the O-linked N-acetylglucosamine transferase OGT1 and several transcription factors. 27705803 5 3 theme O-linked 687:694 arg1 transferase 716:726 the O-linked N-acetylglucosamine transferase 683:726 the O-linked N-acetylglucosamine transferase OGT1 683:731 We identified two human PRC2 complexes and two PR-DUB deubiquitination complexes, which contain the O-linked N-acetylglucosamine transferase OGT1 and several transcription factors. 27705803 6 4 theme differential 918:929 arg1 impact 931:936 differential impact 918:936 differential impact on cellular processes in mammals 918:969 Finally, genome-wide profiling of PR-DUB components indicated that the human PR-DUB and PRC1 complexes bind distinct sets of target genes, suggesting differential impact on cellular processes in mammals. 27705803 4 5 theme target 573:578 arg1 genes 580:584 target genes 573:584 target genes 573:584 Moreover, our analysis identified PcG interactors linking them to the PcG system, thus providing insight into the molecular function of PcG complexes and mechanisms of recruitment to target genes. 27705803 3 6 theme protein 318:324 arg1 network 338:344 Our high-density protein interaction network 301:344 Our high-density protein interaction network 301:344 Our high-density protein interaction network uncovered a diverse range of PcG complexes. 27705803 4 7 theme molecular 504:512 arg1 function 514:521 the molecular function 500:521 the molecular function of PcG complexes 500:538 Moreover, our analysis identified PcG interactors linking them to the PcG system, thus providing insight into the molecular function of PcG complexes and mechanisms of recruitment to target genes. 27705803 5 8 theme deubiquitination 641:656 arg1 complexes 658:666 two PR-DUB deubiquitination complexes 630:666 two PR-DUB deubiquitination complexes 630:666 We identified two human PRC2 complexes and two PR-DUB deubiquitination complexes, which contain the O-linked N-acetylglucosamine transferase OGT1 and several transcription factors. 27705803 6 9 theme PR-DUB 845:850 arg1 complexes 861:869 the human PR-DUB and PRC1 complexes 835:869 the human PR-DUB and PRC1 complexes 835:869 Finally, genome-wide profiling of PR-DUB components indicated that the human PR-DUB and PRC1 complexes bind distinct sets of target genes, suggesting differential impact on cellular processes in mammals. 27705803 1 10 theme epigenetic 140:149 arg1 memory 151:156 epigenetic memory 140:156 epigenetic memory in higher eukaryotes 140:177 Polycomb group (PcG) proteins are major determinants of gene silencing and epigenetic memory in higher eukaryotes. 27705803 3 11 theme diverse 358:364 arg1 range 366:370 a diverse range 356:370 a diverse range of PcG complexes 356:387 Our high-density protein interaction network uncovered a diverse range of PcG complexes. 27705803 6 12 theme human 839:843 arg1 PR-DUB 845:850 human PR-DUB 839:850 human PR-DUB 839:850 Finally, genome-wide profiling of PR-DUB components indicated that the human PR-DUB and PRC1 complexes bind distinct sets of target genes, suggesting differential impact on cellular processes in mammals. 27705803 2 13 theme mass 273:276 arg1 approach 291:298 a robust affinity purification mass spectrometry approach 242:298 a robust affinity purification mass spectrometry approach 242:298 Here, we systematically mapped the human PcG complexome using a robust affinity purification mass spectrometry approach. 27705803 5 14 theme transcription 745:757 arg1 factors 759:765 several transcription factors 737:765 several transcription factors 737:765 We identified two human PRC2 complexes and two PR-DUB deubiquitination complexes, which contain the O-linked N-acetylglucosamine transferase OGT1 and several transcription factors. 27705803 5 15 theme transferase 716:726 arg1 OGT1 728:731 the O-linked N-acetylglucosamine transferase OGT1 683:731 the O-linked N-acetylglucosamine transferase OGT1 683:731 We identified two human PRC2 complexes and two PR-DUB deubiquitination complexes, which contain the O-linked N-acetylglucosamine transferase OGT1 and several transcription factors. 27705803 2 16 theme purification 260:271 arg1 approach 291:298 a robust affinity purification mass spectrometry approach 242:298 a robust affinity purification mass spectrometry approach 242:298 Here, we systematically mapped the human PcG complexome using a robust affinity purification mass spectrometry approach. 27705803 5 17 theme PRC2 611:614 arg1 complexes 616:624 two human PRC2 complexes 601:624 two human PRC2 complexes 601:624 We identified two human PRC2 complexes and two PR-DUB deubiquitination complexes, which contain the O-linked N-acetylglucosamine transferase OGT1 and several transcription factors. 27705803 5 18 theme human 605:609 arg1 complexes 616:624 two human PRC2 complexes 601:624 two human PRC2 complexes 601:624 We identified two human PRC2 complexes and two PR-DUB deubiquitination complexes, which contain the O-linked N-acetylglucosamine transferase OGT1 and several transcription factors. 27705803 1 19 theme Polycomb 65:72 arg1 determinants 105:116 major determinants 99:116 major determinants of gene silencing 99:134 Polycomb group (PcG) proteins are major determinants of gene silencing and epigenetic memory in higher eukaryotes. 27705803 1 19 theme Polycomb 65:72 arg1 proteins 86:93 Polycomb group (PcG) proteins 65:93 Polycomb group (PcG) proteins 65:93 Polycomb group (PcG) proteins are major determinants of gene silencing and epigenetic memory in higher eukaryotes. 27705803 1 20 from determinants 105:116 arg1 eukaryotes 168:177 higher eukaryotes 161:177 higher eukaryotes 161:177 Polycomb group (PcG) proteins are major determinants of gene silencing and epigenetic memory in higher eukaryotes. 27705803 2 21 theme robust 244:249 arg1 approach 291:298 a robust affinity purification mass spectrometry approach 242:298 a robust affinity purification mass spectrometry approach 242:298 Here, we systematically mapped the human PcG complexome using a robust affinity purification mass spectrometry approach. 27705803 5 22 contain contain 675:681 arg2 OGT1 728:731 the O-linked N-acetylglucosamine transferase OGT1 683:731 the O-linked N-acetylglucosamine transferase OGT1 683:731 We identified two human PRC2 complexes and two PR-DUB deubiquitination complexes, which contain the O-linked N-acetylglucosamine transferase OGT1 and several transcription factors. 27705803 5 22 contain contain 675:681 arg1 complexes 658:666 two PR-DUB deubiquitination complexes 630:666 two PR-DUB deubiquitination complexes 630:666 We identified two human PRC2 complexes and two PR-DUB deubiquitination complexes, which contain the O-linked N-acetylglucosamine transferase OGT1 and several transcription factors. 27705803 5 22 contain contain 675:681 arg1 complexes 616:624 two human PRC2 complexes 601:624 two human PRC2 complexes 601:624 We identified two human PRC2 complexes and two PR-DUB deubiquitination complexes, which contain the O-linked N-acetylglucosamine transferase OGT1 and several transcription factors. 27705803 5 22 contain contain 675:681 arg2 factors 759:765 several transcription factors 737:765 several transcription factors 737:765 We identified two human PRC2 complexes and two PR-DUB deubiquitination complexes, which contain the O-linked N-acetylglucosamine transferase OGT1 and several transcription factors. 27705803 0 23 theme High-Density 2:13 arg1 Map 15:17 A High-Density Map 0:17 A High-Density Map for Navigating the Human Polycomb Complexome 0:62 A High-Density Map for Navigating the Human Polycomb Complexome. 27705803 6 24 theme genes 900:904 arg1 sets 885:888 distinct sets 876:888 distinct sets of target genes 876:904 Finally, genome-wide profiling of PR-DUB components indicated that the human PR-DUB and PRC1 complexes bind distinct sets of target genes, suggesting differential impact on cellular processes in mammals. 27705803 6 24 theme genes 900:904 arg1 genes 900:904 target genes 893:904 target genes 893:904 Finally, genome-wide profiling of PR-DUB components indicated that the human PR-DUB and PRC1 complexes bind distinct sets of target genes, suggesting differential impact on cellular processes in mammals. 27705803 6 25 theme components 809:818 arg1 profiling 789:797 genome-wide profiling 777:797 genome-wide profiling of PR-DUB components 777:818 Finally, genome-wide profiling of PR-DUB components indicated that the human PR-DUB and PRC1 complexes bind distinct sets of target genes, suggesting differential impact on cellular processes in mammals. 27705803 1 26 theme higher 161:166 arg1 eukaryotes 168:177 higher eukaryotes 161:177 higher eukaryotes 161:177 Polycomb group (PcG) proteins are major determinants of gene silencing and epigenetic memory in higher eukaryotes. 27705803 6 27 theme PR-DUB 802:807 arg1 components 809:818 PR-DUB components 802:818 PR-DUB components 802:818 Finally, genome-wide profiling of PR-DUB components indicated that the human PR-DUB and PRC1 complexes bind distinct sets of target genes, suggesting differential impact on cellular processes in mammals. 27705803 1 28 theme PcG 81:83 arg1 determinants 105:116 major determinants 99:116 major determinants of gene silencing 99:134 Polycomb group (PcG) proteins are major determinants of gene silencing and epigenetic memory in higher eukaryotes. 27705803 1 28 theme PcG 81:83 arg1 proteins 86:93 Polycomb group (PcG) proteins 65:93 Polycomb group (PcG) proteins 65:93 Polycomb group (PcG) proteins are major determinants of gene silencing and epigenetic memory in higher eukaryotes. 27705803 5 29 theme N-acetylglucosamine 696:714 arg1 transferase 716:726 the O-linked N-acetylglucosamine transferase 683:726 the O-linked N-acetylglucosamine transferase OGT1 683:731 We identified two human PRC2 complexes and two PR-DUB deubiquitination complexes, which contain the O-linked N-acetylglucosamine transferase OGT1 and several transcription factors. 27705803 3 30 theme PcG 375:377 arg1 complexes 379:387 PcG complexes 375:387 PcG complexes 375:387 Our high-density protein interaction network uncovered a diverse range of PcG complexes. 27705803 4 31 theme recruitment 558:568 arg1 mechanisms 544:553 mechanisms 544:553 mechanisms of recruitment to target genes 544:584 Moreover, our analysis identified PcG interactors linking them to the PcG system, thus providing insight into the molecular function of PcG complexes and mechanisms of recruitment to target genes. 27705803 4 31 theme recruitment 558:568 arg1 function 514:521 the molecular function 500:521 the molecular function of PcG complexes 500:538 Moreover, our analysis identified PcG interactors linking them to the PcG system, thus providing insight into the molecular function of PcG complexes and mechanisms of recruitment to target genes. 27705803 2 32 theme affinity 251:258 arg1 approach 291:298 a robust affinity purification mass spectrometry approach 242:298 a robust affinity purification mass spectrometry approach 242:298 Here, we systematically mapped the human PcG complexome using a robust affinity purification mass spectrometry approach. 27705803 6 33 theme target 893:898 arg1 genes 900:904 target genes 893:904 target genes 893:904 Finally, genome-wide profiling of PR-DUB components indicated that the human PR-DUB and PRC1 complexes bind distinct sets of target genes, suggesting differential impact on cellular processes in mammals. 27705803 2 34 theme spectrometry 278:289 arg1 approach 291:298 a robust affinity purification mass spectrometry approach 242:298 a robust affinity purification mass spectrometry approach 242:298 Here, we systematically mapped the human PcG complexome using a robust affinity purification mass spectrometry approach. 27705803 5 35 link O-linked 687:694 arg1 transferase 716:726 the O-linked N-acetylglucosamine transferase 683:726 the O-linked N-acetylglucosamine transferase OGT1 683:731 We identified two human PRC2 complexes and two PR-DUB deubiquitination complexes, which contain the O-linked N-acetylglucosamine transferase OGT1 and several transcription factors. 27705803 2 36 theme human 215:219 arg1 complexome 225:234 the human PcG complexome 211:234 the human PcG complexome 211:234 Here, we systematically mapped the human PcG complexome using a robust affinity purification mass spectrometry approach. 27705803 4 37 theme PcG 460:462 arg1 system 464:469 the PcG system 456:469 the PcG system 456:469 Moreover, our analysis identified PcG interactors linking them to the PcG system, thus providing insight into the molecular function of PcG complexes and mechanisms of recruitment to target genes. 27705803 0 38 theme Polycomb 44:51 arg1 Complexome 53:62 the Human Polycomb Complexome 34:62 the Human Polycomb Complexome 34:62 A High-Density Map for Navigating the Human Polycomb Complexome. 27705803 5 39 theme several 737:743 arg1 factors 759:765 several transcription factors 737:765 several transcription factors 737:765 We identified two human PRC2 complexes and two PR-DUB deubiquitination complexes, which contain the O-linked N-acetylglucosamine transferase OGT1 and several transcription factors. 27705803 6 40 theme distinct 876:883 arg1 sets 885:888 distinct sets 876:888 distinct sets of target genes 876:904 Finally, genome-wide profiling of PR-DUB components indicated that the human PR-DUB and PRC1 complexes bind distinct sets of target genes, suggesting differential impact on cellular processes in mammals. 27705803 6 40 theme distinct 876:883 arg1 genes 900:904 target genes 893:904 target genes 893:904 Finally, genome-wide profiling of PR-DUB components indicated that the human PR-DUB and PRC1 complexes bind distinct sets of target genes, suggesting differential impact on cellular processes in mammals. 27705803 6 41 theme genome-wide 777:787 arg1 profiling 789:797 genome-wide profiling 777:797 genome-wide profiling of PR-DUB components 777:818 Finally, genome-wide profiling of PR-DUB components indicated that the human PR-DUB and PRC1 complexes bind distinct sets of target genes, suggesting differential impact on cellular processes in mammals. 27705803 0 42 theme Human 38:42 arg1 Complexome 53:62 the Human Polycomb Complexome 34:62 the Human Polycomb Complexome 34:62 A High-Density Map for Navigating the Human Polycomb Complexome. 27705803 4 43 theme complexes 530:538 arg1 mechanisms 544:553 mechanisms 544:553 mechanisms of recruitment to target genes 544:584 Moreover, our analysis identified PcG interactors linking them to the PcG system, thus providing insight into the molecular function of PcG complexes and mechanisms of recruitment to target genes. 27705803 4 43 theme complexes 530:538 arg1 function 514:521 the molecular function 500:521 the molecular function of PcG complexes 500:538 Moreover, our analysis identified PcG interactors linking them to the PcG system, thus providing insight into the molecular function of PcG complexes and mechanisms of recruitment to target genes. 27705803 4 44 theme PcG 424:426 arg1 interactors 428:438 PcG interactors 424:438 PcG interactors linking them to the PcG system 424:469 Moreover, our analysis identified PcG interactors linking them to the PcG system, thus providing insight into the molecular function of PcG complexes and mechanisms of recruitment to target genes. 27705803 1 45 theme major 99:103 arg1 determinants 105:116 major determinants 99:116 major determinants of gene silencing 99:134 Polycomb group (PcG) proteins are major determinants of gene silencing and epigenetic memory in higher eukaryotes. 27705803 1 45 theme major 99:103 arg1 proteins 86:93 Polycomb group (PcG) proteins 65:93 Polycomb group (PcG) proteins 65:93 Polycomb group (PcG) proteins are major determinants of gene silencing and epigenetic memory in higher eukaryotes. 27705803 4 46 theme PcG 526:528 arg1 complexes 530:538 PcG complexes 526:538 PcG complexes 526:538 Moreover, our analysis identified PcG interactors linking them to the PcG system, thus providing insight into the molecular function of PcG complexes and mechanisms of recruitment to target genes. 27705803 1 47 theme group 74:78 arg1 determinants 105:116 major determinants 99:116 major determinants of gene silencing 99:134 Polycomb group (PcG) proteins are major determinants of gene silencing and epigenetic memory in higher eukaryotes. 27705803 1 47 theme group 74:78 arg1 proteins 86:93 Polycomb group (PcG) proteins 65:93 Polycomb group (PcG) proteins 65:93 Polycomb group (PcG) proteins are major determinants of gene silencing and epigenetic memory in higher eukaryotes. 27705803 6 48 theme PRC1 856:859 arg1 complexes 861:869 the human PR-DUB and PRC1 complexes 835:869 the human PR-DUB and PRC1 complexes 835:869 Finally, genome-wide profiling of PR-DUB components indicated that the human PR-DUB and PRC1 complexes bind distinct sets of target genes, suggesting differential impact on cellular processes in mammals. 27705803 3 49 theme interaction 326:336 arg1 network 338:344 Our high-density protein interaction network 301:344 Our high-density protein interaction network 301:344 Our high-density protein interaction network uncovered a diverse range of PcG complexes. 27705803 1 50 theme gene 121:124 arg1 silencing 126:134 gene silencing 121:134 gene silencing 121:134 Polycomb group (PcG) proteins are major determinants of gene silencing and epigenetic memory in higher eukaryotes. 27705803 3 51 theme complexes 379:387 arg1 range 366:370 a diverse range 356:370 a diverse range of PcG complexes 356:387 Our high-density protein interaction network uncovered a diverse range of PcG complexes. 27705803 6 52 from impact 931:936 arg1 processes 950:958 cellular processes 941:958 cellular processes in mammals 941:969 Finally, genome-wide profiling of PR-DUB components indicated that the human PR-DUB and PRC1 complexes bind distinct sets of target genes, suggesting differential impact on cellular processes in mammals. 27705803 2 53 theme PcG 221:223 arg1 complexome 225:234 the human PcG complexome 211:234 the human PcG complexome 211:234 Here, we systematically mapped the human PcG complexome using a robust affinity purification mass spectrometry approach. 27705803 1 54 from memory 151:156 arg1 eukaryotes 168:177 higher eukaryotes 161:177 higher eukaryotes 161:177 Polycomb group (PcG) proteins are major determinants of gene silencing and epigenetic memory in higher eukaryotes. 27705803 1 55 theme silencing 126:134 arg1 determinants 105:116 major determinants 99:116 major determinants of gene silencing 99:134 Polycomb group (PcG) proteins are major determinants of gene silencing and epigenetic memory in higher eukaryotes. 27705803 1 55 theme silencing 126:134 arg1 memory 151:156 epigenetic memory 140:156 epigenetic memory in higher eukaryotes 140:177 Polycomb group (PcG) proteins are major determinants of gene silencing and epigenetic memory in higher eukaryotes. 27705803 1 55 theme silencing 126:134 arg1 proteins 86:93 Polycomb group (PcG) proteins 65:93 Polycomb group (PcG) proteins 65:93 Polycomb group (PcG) proteins are major determinants of gene silencing and epigenetic memory in higher eukaryotes. 27705803 6 56 from processes 950:958 arg1 mammals 963:969 mammals 963:969 mammals 963:969 Finally, genome-wide profiling of PR-DUB components indicated that the human PR-DUB and PRC1 complexes bind distinct sets of target genes, suggesting differential impact on cellular processes in mammals. 27482661 12 0 from effect 2289:2294 arg1 cells 2306:2310 immune cells 2299:2310 immune cells 2299:2310 Therefore, our data indicate that CD8α1 may have immunoregulatory activity by regulating the expression of proinflammatory or anti-inflammatory cytokines via its effect on immune cells. 27482661 10 1 theme transcription 1755:1767 arg1 factors 1769:1775 transcription factors 1755:1775 transcription factors 1755:1775 The results showed that chicken CD8α1 is a key regulator of the expression of genes that are associated and cooperate with transcription factors in the major histocompatibility complex class I and II promoter regions and activates Janus kinase (JAK) 1/2, signal transducer and activator of transcription (STAT), and suppressor of cytokine signaling (SOCS) 1 signaling-related genes. 27482661 12 2 theme immunoregulatory 2176:2191 arg1 activity 2193:2200 immunoregulatory activity 2176:2200 immunoregulatory activity 2176:2200 Therefore, our data indicate that CD8α1 may have immunoregulatory activity by regulating the expression of proinflammatory or anti-inflammatory cytokines via its effect on immune cells. 27482661 1 3 theme differentiation 216:230 arg1 family 247:252 differentiation 8 alpha (CD8a) family 216:252 differentiation 8 alpha (CD8a) family 216:252 We provide the first description of cloning and of structural and functional analysis of a novel variant in the chicken cluster of differentiation 8 alpha (CD8a) family, termed the CD8α X1 (CD8α1) gene. 27482661 9 4 theme cytokine 1514:1521 arg1 response 1523:1530 cytokine response 1514:1530 cytokine response 1514:1530 Moreover, we analyzed the signal transduction and cytokine response to CD8α1 treatment to determine the specific biological functions of chicken CD8α1 in immune cells. 27482661 10 5 theme transcription 1922:1934 arg1 activator 1909:1917 activator 1909:1917 activator 1909:1917 The results showed that chicken CD8α1 is a key regulator of the expression of genes that are associated and cooperate with transcription factors in the major histocompatibility complex class I and II promoter regions and activates Janus kinase (JAK) 1/2, signal transducer and activator of transcription (STAT), and suppressor of cytokine signaling (SOCS) 1 signaling-related genes. 27482661 10 5 theme transcription 1922:1934 arg1 suppressor 1948:1957 suppressor 1948:1957 suppressor of cytokine signaling (SOCS) 1 1948:1988 The results showed that chicken CD8α1 is a key regulator of the expression of genes that are associated and cooperate with transcription factors in the major histocompatibility complex class I and II promoter regions and activates Janus kinase (JAK) 1/2, signal transducer and activator of transcription (STAT), and suppressor of cytokine signaling (SOCS) 1 signaling-related genes. 27482661 10 5 theme transcription 1922:1934 arg1 transducer 1894:1903 signal transducer 1887:1903 signal transducer 1887:1903 The results showed that chicken CD8α1 is a key regulator of the expression of genes that are associated and cooperate with transcription factors in the major histocompatibility complex class I and II promoter regions and activates Janus kinase (JAK) 1/2, signal transducer and activator of transcription (STAT), and suppressor of cytokine signaling (SOCS) 1 signaling-related genes. 27482661 10 5 theme transcription 1922:1934 arg1 JAK 1877:1879 Janus kinase (JAK) 1/2 1863:1884 Janus kinase (JAK) 1/2 1863:1884 The results showed that chicken CD8α1 is a key regulator of the expression of genes that are associated and cooperate with transcription factors in the major histocompatibility complex class I and II promoter regions and activates Janus kinase (JAK) 1/2, signal transducer and activator of transcription (STAT), and suppressor of cytokine signaling (SOCS) 1 signaling-related genes. 27482661 10 5 theme transcription 1922:1934 arg1 STAT 1937:1940 STAT 1937:1940 STAT 1937:1940 The results showed that chicken CD8α1 is a key regulator of the expression of genes that are associated and cooperate with transcription factors in the major histocompatibility complex class I and II promoter regions and activates Janus kinase (JAK) 1/2, signal transducer and activator of transcription (STAT), and suppressor of cytokine signaling (SOCS) 1 signaling-related genes. 27482661 9 6 theme CD8α1 1535:1539 arg1 treatment 1541:1549 CD8α1 treatment 1535:1549 CD8α1 treatment 1535:1549 Moreover, we analyzed the signal transduction and cytokine response to CD8α1 treatment to determine the specific biological functions of chicken CD8α1 in immune cells. 27482661 10 7 theme complex 1809:1815 arg1 class 1817:1821 the major histocompatibility complex class I 1780:1823 the major histocompatibility complex class I 1780:1823 The results showed that chicken CD8α1 is a key regulator of the expression of genes that are associated and cooperate with transcription factors in the major histocompatibility complex class I and II promoter regions and activates Janus kinase (JAK) 1/2, signal transducer and activator of transcription (STAT), and suppressor of cytokine signaling (SOCS) 1 signaling-related genes. 27482661 1 8 theme alpha 234:238 arg1 family 247:252 differentiation 8 alpha (CD8a) family 216:252 differentiation 8 alpha (CD8a) family 216:252 We provide the first description of cloning and of structural and functional analysis of a novel variant in the chicken cluster of differentiation 8 alpha (CD8a) family, termed the CD8α X1 (CD8α1) gene. 27482661 4 9 theme strand 716:721 arg1 sequences 770:778 the A β strand and complementarity-determining region 1 and 2 sequences 708:778 the A β strand and complementarity-determining region 1 and 2 sequences 708:778 In contrast, the O-linked glycosylation sites (XPXX motif) are not found in the chicken CD8α1 sequence, and the A β strand and complementarity-determining region 1 and 2 sequences are poorly conserved between chicken CD8α1 and avian CD8α. 27482661 4 10 link O-linked 617:624 arg1 motif 652:656 XPXX motif 647:656 XPXX motif 647:656 In contrast, the O-linked glycosylation sites (XPXX motif) are not found in the chicken CD8α1 sequence, and the A β strand and complementarity-determining region 1 and 2 sequences are poorly conserved between chicken CD8α1 and avian CD8α. 27482661 4 10 link O-linked 617:624 arg1 sites 640:644 the O-linked glycosylation sites 613:644 the O-linked glycosylation sites (XPXX motif) 613:657 In contrast, the O-linked glycosylation sites (XPXX motif) are not found in the chicken CD8α1 sequence, and the A β strand and complementarity-determining region 1 and 2 sequences are poorly conserved between chicken CD8α1 and avian CD8α. 27482661 10 11 theme major 1784:1788 arg1 class 1817:1821 the major histocompatibility complex class I 1780:1823 the major histocompatibility complex class I 1780:1823 The results showed that chicken CD8α1 is a key regulator of the expression of genes that are associated and cooperate with transcription factors in the major histocompatibility complex class I and II promoter regions and activates Janus kinase (JAK) 1/2, signal transducer and activator of transcription (STAT), and suppressor of cytokine signaling (SOCS) 1 signaling-related genes. 27482661 6 12 theme kinase 1137:1142 arg1 p56 1153:1155 p56 1153:1155 p56 1153:1155 Moreover, the motif (CXCP) that is thought to be responsible for binding the p56 lymphocyte cell kinase subunit (p56) is missing in the CD8α1 sequence. 27482661 6 12 theme kinase 1137:1142 arg1 subunit 1144:1150 the p56 lymphocyte cell kinase subunit 1113:1150 the p56 lymphocyte cell kinase subunit (p56) 1113:1156 Moreover, the motif (CXCP) that is thought to be responsible for binding the p56 lymphocyte cell kinase subunit (p56) is missing in the CD8α1 sequence. 27482661 4 13 theme complementarity-determining 727:753 arg1 region 755:760 complementarity-determining region 1 and 2 727:768 region 755:760 In contrast, the O-linked glycosylation sites (XPXX motif) are not found in the chicken CD8α1 sequence, and the A β strand and complementarity-determining region 1 and 2 sequences are poorly conserved between chicken CD8α1 and avian CD8α. 27482661 11 14 theme innate 2102:2107 arg1 responses 2116:2124 innate immune responses 2102:2124 proinflammatory cytokines as well as innate immune responses 2065:2124 Immune cells that express functional CD8α1 induce proinflammatory cytokines as well as innate immune responses. 27482661 5 15 dep show 904:907 arg1 whereas 946:952 whereas 946:952 whereas 946:952 Furthermore, the alignment showed that the transmembrane regions show relatively high sequence similarity, whereas the cytoplasmic regions show relatively low similarity, indicating poor conservation. 27482661 10 16 theme II 1829:1830 arg1 regions 1841:1847 II promoter regions 1829:1847 II promoter regions 1829:1847 The results showed that chicken CD8α1 is a key regulator of the expression of genes that are associated and cooperate with transcription factors in the major histocompatibility complex class I and II promoter regions and activates Janus kinase (JAK) 1/2, signal transducer and activator of transcription (STAT), and suppressor of cytokine signaling (SOCS) 1 signaling-related genes. 27482661 6 17 theme lymphocyte 1121:1130 arg1 p56 1153:1155 p56 1153:1155 p56 1153:1155 Moreover, the motif (CXCP) that is thought to be responsible for binding the p56 lymphocyte cell kinase subunit (p56) is missing in the CD8α1 sequence. 27482661 6 17 theme lymphocyte 1121:1130 arg1 subunit 1144:1150 the p56 lymphocyte cell kinase subunit 1113:1150 the p56 lymphocyte cell kinase subunit (p56) 1113:1156 Moreover, the motif (CXCP) that is thought to be responsible for binding the p56 lymphocyte cell kinase subunit (p56) is missing in the CD8α1 sequence. 27482661 1 18 theme analysis 162:169 arg1 description 106:116 the first description 96:116 the first description of cloning and of structural and functional analysis of a novel variant in the chicken cluster of differentiation 8 alpha (CD8a) family, termed the CD8α X1 (CD8α1) gene 96:285 We provide the first description of cloning and of structural and functional analysis of a novel variant in the chicken cluster of differentiation 8 alpha (CD8a) family, termed the CD8α X1 (CD8α1) gene. 27482661 4 19 theme chicken 809:815 arg1 CD8α1 817:821 chicken CD8α1 809:821 chicken CD8α1 809:821 In contrast, the O-linked glycosylation sites (XPXX motif) are not found in the chicken CD8α1 sequence, and the A β strand and complementarity-determining region 1 and 2 sequences are poorly conserved between chicken CD8α1 and avian CD8α. 27482661 10 20 theme chicken 1656:1662 arg1 regulator 1679:1687 a key regulator 1673:1687 a key regulator of the expression of genes that are associated and cooperate with transcription factors in the major histocompatibility complex class I and II promoter regions 1673:1847 The results showed that chicken CD8α1 is a key regulator of the expression of genes that are associated and cooperate with transcription factors in the major histocompatibility complex class I and II promoter regions and activates Janus kinase (JAK) 1/2, signal transducer and activator of transcription (STAT), and suppressor of cytokine signaling (SOCS) 1 signaling-related genes. 27482661 10 20 theme chicken 1656:1662 arg1 CD8α1 1664:1668 chicken CD8α1 1656:1668 chicken CD8α1 1656:1668 The results showed that chicken CD8α1 is a key regulator of the expression of genes that are associated and cooperate with transcription factors in the major histocompatibility complex class I and II promoter regions and activates Janus kinase (JAK) 1/2, signal transducer and activator of transcription (STAT), and suppressor of cytokine signaling (SOCS) 1 signaling-related genes. 27482661 7 21 theme chicken 1250:1256 arg1 CD8α 1258:1261 chicken CD8α 1250:1261 chicken CD8α 1250:1261 The chicken CD8α1 genomic structure is similar to that of chicken CD8α, but their protein structures differ. 27482661 5 22 theme cytoplasmic 958:968 arg1 regions 970:976 the cytoplasmic regions 954:976 the cytoplasmic regions 954:976 Furthermore, the alignment showed that the transmembrane regions show relatively high sequence similarity, whereas the cytoplasmic regions show relatively low similarity, indicating poor conservation. 27482661 9 23 theme specific 1568:1575 arg1 functions 1588:1596 the specific biological functions 1564:1596 the specific biological functions of chicken CD8α1 in immune cells 1564:1629 Moreover, we analyzed the signal transduction and cytokine response to CD8α1 treatment to determine the specific biological functions of chicken CD8α1 in immune cells. 27482661 6 24 theme p56 1117:1119 arg1 p56 1153:1155 p56 1153:1155 p56 1153:1155 Moreover, the motif (CXCP) that is thought to be responsible for binding the p56 lymphocyte cell kinase subunit (p56) is missing in the CD8α1 sequence. 27482661 6 24 theme p56 1117:1119 arg1 subunit 1144:1150 the p56 lymphocyte cell kinase subunit 1113:1150 the p56 lymphocyte cell kinase subunit (p56) 1113:1156 Moreover, the motif (CXCP) that is thought to be responsible for binding the p56 lymphocyte cell kinase subunit (p56) is missing in the CD8α1 sequence. 27482661 10 25 theme cytokine 1962:1969 arg1 SOCS 1982:1985 cytokine signaling (SOCS) 1 1962:1988 cytokine signaling (SOCS) 1 1962:1988 The results showed that chicken CD8α1 is a key regulator of the expression of genes that are associated and cooperate with transcription factors in the major histocompatibility complex class I and II promoter regions and activates Janus kinase (JAK) 1/2, signal transducer and activator of transcription (STAT), and suppressor of cytokine signaling (SOCS) 1 signaling-related genes. 27482661 1 26 theme variant 182:188 arg1 analysis 162:169 structural and functional analysis 136:169 structural and functional analysis of a novel variant in the chicken cluster of differentiation 8 alpha (CD8a) family, termed the CD8α X1 (CD8α1) gene 136:285 We provide the first description of cloning and of structural and functional analysis of a novel variant in the chicken cluster of differentiation 8 alpha (CD8a) family, termed the CD8α X1 (CD8α1) gene. 27482661 8 27 dep CD8α1 1343:1347 arg1 grouped 1349:1355 grouped 1349:1355 CD8α1 grouped with known avian CD8α sequences 1343:1387 Phylogenetic analysis showed that chicken CD8α1 grouped with known avian CD8α sequences but was somewhat distantly related to the CD8α molecules of other species. 27482661 10 28 theme signaling-related 1990:2006 arg1 genes 2008:2012 signaling-related genes 1990:2012 signaling-related genes 1990:2012 The results showed that chicken CD8α1 is a key regulator of the expression of genes that are associated and cooperate with transcription factors in the major histocompatibility complex class I and II promoter regions and activates Janus kinase (JAK) 1/2, signal transducer and activator of transcription (STAT), and suppressor of cytokine signaling (SOCS) 1 signaling-related genes. 27482661 4 29 theme O-linked 617:624 arg1 motif 652:656 XPXX motif 647:656 XPXX motif 647:656 In contrast, the O-linked glycosylation sites (XPXX motif) are not found in the chicken CD8α1 sequence, and the A β strand and complementarity-determining region 1 and 2 sequences are poorly conserved between chicken CD8α1 and avian CD8α. 27482661 4 29 theme O-linked 617:624 arg1 sites 640:644 the O-linked glycosylation sites 613:644 the O-linked glycosylation sites (XPXX motif) 613:657 In contrast, the O-linked glycosylation sites (XPXX motif) are not found in the chicken CD8α1 sequence, and the A β strand and complementarity-determining region 1 and 2 sequences are poorly conserved between chicken CD8α1 and avian CD8α. 27482661 1 30 from cluster 205:211 arg1 analysis 162:169 structural and functional analysis 136:169 structural and functional analysis of a novel variant in the chicken cluster of differentiation 8 alpha (CD8a) family, termed the CD8α X1 (CD8α1) gene 136:285 We provide the first description of cloning and of structural and functional analysis of a novel variant in the chicken cluster of differentiation 8 alpha (CD8a) family, termed the CD8α X1 (CD8α1) gene. 27482661 3 31 theme cysteine 507:514 arg1 residues 516:523 cysteine residues 507:523 cysteine residues that are involved in disulfide bonding to form the V domain 507:583 For example, cysteine residues that are involved in disulfide bonding to form the V domain are conserved. 27482661 9 32 theme chicken 1601:1607 arg1 CD8α1 1609:1613 chicken CD8α1 1601:1613 chicken CD8α1 1601:1613 Moreover, we analyzed the signal transduction and cytokine response to CD8α1 treatment to determine the specific biological functions of chicken CD8α1 in immune cells. 27482661 3 33 theme disulfide 546:554 arg1 bonding 556:562 disulfide bonding 546:562 disulfide bonding 546:562 For example, cysteine residues that are involved in disulfide bonding to form the V domain are conserved. 27482661 12 34 contain have 2171:2174 arg2 activity 2193:2200 immunoregulatory activity 2176:2200 immunoregulatory activity 2176:2200 Therefore, our data indicate that CD8α1 may have immunoregulatory activity by regulating the expression of proinflammatory or anti-inflammatory cytokines via its effect on immune cells. 27482661 12 34 contain have 2171:2174 arg1 CD8α1 2161:2165 CD8α1 2161:2165 CD8α1 2161:2165 Therefore, our data indicate that CD8α1 may have immunoregulatory activity by regulating the expression of proinflammatory or anti-inflammatory cytokines via its effect on immune cells. 27482661 7 35 theme CD8α1 1204:1208 arg1 structure 1218:1226 The chicken CD8α1 genomic structure 1192:1226 The chicken CD8α1 genomic structure 1192:1226 The chicken CD8α1 genomic structure is similar to that of chicken CD8α, but their protein structures differ. 27482661 7 35 theme CD8α1 1204:1208 arg1 similar 1231:1237 similar 1231:1237 similar 1231:1237 The chicken CD8α1 genomic structure is similar to that of chicken CD8α, but their protein structures differ. 27482661 10 36 theme kinase 1869:1874 arg1 JAK 1877:1879 Janus kinase (JAK) 1/2 1863:1884 Janus kinase (JAK) 1/2 1863:1884 The results showed that chicken CD8α1 is a key regulator of the expression of genes that are associated and cooperate with transcription factors in the major histocompatibility complex class I and II promoter regions and activates Janus kinase (JAK) 1/2, signal transducer and activator of transcription (STAT), and suppressor of cytokine signaling (SOCS) 1 signaling-related genes. 27482661 0 37 theme CD8α 60:63 arg1 variant 65:71 a novel chicken CD8α variant X1 (CD8α1) 44:82 a novel chicken CD8α variant X1 (CD8α1) 44:82 Characterization and functional analyses of a novel chicken CD8α variant X1 (CD8α1). 27482661 5 38 theme poor 1021:1024 arg1 conservation 1026:1037 poor conservation 1021:1037 poor conservation 1021:1037 Furthermore, the alignment showed that the transmembrane regions show relatively high sequence similarity, whereas the cytoplasmic regions show relatively low similarity, indicating poor conservation. 27482661 10 39 theme key 1675:1677 arg1 regulator 1679:1687 a key regulator 1673:1687 a key regulator of the expression of genes that are associated and cooperate with transcription factors in the major histocompatibility complex class I and II promoter regions 1673:1847 The results showed that chicken CD8α1 is a key regulator of the expression of genes that are associated and cooperate with transcription factors in the major histocompatibility complex class I and II promoter regions and activates Janus kinase (JAK) 1/2, signal transducer and activator of transcription (STAT), and suppressor of cytokine signaling (SOCS) 1 signaling-related genes. 27482661 10 39 theme key 1675:1677 arg1 CD8α1 1664:1668 chicken CD8α1 1656:1668 chicken CD8α1 1656:1668 The results showed that chicken CD8α1 is a key regulator of the expression of genes that are associated and cooperate with transcription factors in the major histocompatibility complex class I and II promoter regions and activates Janus kinase (JAK) 1/2, signal transducer and activator of transcription (STAT), and suppressor of cytokine signaling (SOCS) 1 signaling-related genes. 27482661 1 40 theme cloning 121:127 arg1 description 106:116 the first description 96:116 the first description of cloning and of structural and functional analysis of a novel variant in the chicken cluster of differentiation 8 alpha (CD8a) family, termed the CD8α X1 (CD8α1) gene 96:285 We provide the first description of cloning and of structural and functional analysis of a novel variant in the chicken cluster of differentiation 8 alpha (CD8a) family, termed the CD8α X1 (CD8α1) gene. 27482661 2 41 theme residues 412:419 arg1 conservation 393:404 relatively low conservation 378:404 relatively low conservation of AA residues involved in the specific and unique structural domains among CD8α genes 378:491 Multiple alignments of CD8α1 with known CD8α and CD8β sequences of other species revealed relatively low conservation of AA residues involved in the specific and unique structural domains among CD8α genes. 27482661 10 42 theme signal 1887:1892 arg1 transducer 1894:1903 signal transducer 1887:1903 signal transducer 1887:1903 The results showed that chicken CD8α1 is a key regulator of the expression of genes that are associated and cooperate with transcription factors in the major histocompatibility complex class I and II promoter regions and activates Janus kinase (JAK) 1/2, signal transducer and activator of transcription (STAT), and suppressor of cytokine signaling (SOCS) 1 signaling-related genes. 27482661 10 42 theme signal 1887:1892 arg1 STAT 1937:1940 STAT 1937:1940 STAT 1937:1940 The results showed that chicken CD8α1 is a key regulator of the expression of genes that are associated and cooperate with transcription factors in the major histocompatibility complex class I and II promoter regions and activates Janus kinase (JAK) 1/2, signal transducer and activator of transcription (STAT), and suppressor of cytokine signaling (SOCS) 1 signaling-related genes. 27482661 1 43 theme CD8α1 275:279 arg1 gene 282:285 the CD8α X1 (CD8α1) gene 262:285 the CD8α X1 (CD8α1) gene 262:285 We provide the first description of cloning and of structural and functional analysis of a novel variant in the chicken cluster of differentiation 8 alpha (CD8a) family, termed the CD8α X1 (CD8α1) gene. 27482661 2 44 theme unique 450:455 arg1 domains 468:474 the specific and unique structural domains 433:474 the specific and unique structural domains 433:474 Multiple alignments of CD8α1 with known CD8α and CD8β sequences of other species revealed relatively low conservation of AA residues involved in the specific and unique structural domains among CD8α genes. 27482661 8 45 theme avian 1368:1372 arg1 sequences 1379:1387 known avian CD8α sequences 1362:1387 known avian CD8α sequences 1362:1387 Phylogenetic analysis showed that chicken CD8α1 grouped with known avian CD8α sequences but was somewhat distantly related to the CD8α molecules of other species. 27482661 5 46 theme low 994:996 arg1 similarity 998:1007 relatively low similarity 983:1007 relatively low similarity 983:1007 Furthermore, the alignment showed that the transmembrane regions show relatively high sequence similarity, whereas the cytoplasmic regions show relatively low similarity, indicating poor conservation. 27482661 2 47 theme specific 437:444 arg1 domains 468:474 the specific and unique structural domains 433:474 the specific and unique structural domains 433:474 Multiple alignments of CD8α1 with known CD8α and CD8β sequences of other species revealed relatively low conservation of AA residues involved in the specific and unique structural domains among CD8α genes. 27482661 2 48 theme known 322:326 arg1 sequences 342:350 known CD8α and CD8β sequences 322:350 known CD8α and CD8β sequences of other species 322:367 Multiple alignments of CD8α1 with known CD8α and CD8β sequences of other species revealed relatively low conservation of AA residues involved in the specific and unique structural domains among CD8α genes. 27482661 7 49 theme chicken 1196:1202 arg1 structure 1218:1226 The chicken CD8α1 genomic structure 1192:1226 The chicken CD8α1 genomic structure 1192:1226 The chicken CD8α1 genomic structure is similar to that of chicken CD8α, but their protein structures differ. 27482661 7 49 theme chicken 1196:1202 arg1 similar 1231:1237 similar 1231:1237 similar 1231:1237 The chicken CD8α1 genomic structure is similar to that of chicken CD8α, but their protein structures differ. 27482661 4 50 theme XPXX 647:650 arg1 motif 652:656 XPXX motif 647:656 XPXX motif 647:656 In contrast, the O-linked glycosylation sites (XPXX motif) are not found in the chicken CD8α1 sequence, and the A β strand and complementarity-determining region 1 and 2 sequences are poorly conserved between chicken CD8α1 and avian CD8α. 27482661 4 50 theme XPXX 647:650 arg1 sites 640:644 the O-linked glycosylation sites 613:644 the O-linked glycosylation sites (XPXX motif) 613:657 In contrast, the O-linked glycosylation sites (XPXX motif) are not found in the chicken CD8α1 sequence, and the A β strand and complementarity-determining region 1 and 2 sequences are poorly conserved between chicken CD8α1 and avian CD8α. 27482661 2 51 theme CD8α1 311:315 arg1 alignments 297:306 Multiple alignments 288:306 Multiple alignments of CD8α1 with known CD8α and CD8β sequences of other species 288:367 Multiple alignments of CD8α1 with known CD8α and CD8β sequences of other species revealed relatively low conservation of AA residues involved in the specific and unique structural domains among CD8α genes. 27482661 2 52 theme other 355:359 arg1 species 361:367 other species 355:367 other species 355:367 Multiple alignments of CD8α1 with known CD8α and CD8β sequences of other species revealed relatively low conservation of AA residues involved in the specific and unique structural domains among CD8α genes. 27482661 0 53 theme functional 21:30 arg1 analyses 32:39 functional analyses 21:39 functional analyses 21:39 Characterization and functional analyses of a novel chicken CD8α variant X1 (CD8α1). 27482661 10 54 theme genes 1710:1714 arg1 expression 1696:1705 the expression 1692:1705 the expression of genes that are associated and cooperate with transcription factors in the major histocompatibility complex class I and II promoter regions 1692:1847 The results showed that chicken CD8α1 is a key regulator of the expression of genes that are associated and cooperate with transcription factors in the major histocompatibility complex class I and II promoter regions and activates Janus kinase (JAK) 1/2, signal transducer and activator of transcription (STAT), and suppressor of cytokine signaling (SOCS) 1 signaling-related genes. 27482661 2 55 theme low 389:391 arg1 conservation 393:404 relatively low conservation 378:404 relatively low conservation of AA residues involved in the specific and unique structural domains among CD8α genes 378:491 Multiple alignments of CD8α1 with known CD8α and CD8β sequences of other species revealed relatively low conservation of AA residues involved in the specific and unique structural domains among CD8α genes. 27482661 8 56 theme CD8α 1431:1434 arg1 molecules 1436:1444 the CD8α molecules 1427:1444 the CD8α molecules of other species 1427:1461 Phylogenetic analysis showed that chicken CD8α1 grouped with known avian CD8α sequences but was somewhat distantly related to the CD8α molecules of other species. 27482661 10 57 theme expression 1696:1705 arg1 regulator 1679:1687 a key regulator 1673:1687 a key regulator of the expression of genes that are associated and cooperate with transcription factors in the major histocompatibility complex class I and II promoter regions 1673:1847 The results showed that chicken CD8α1 is a key regulator of the expression of genes that are associated and cooperate with transcription factors in the major histocompatibility complex class I and II promoter regions and activates Janus kinase (JAK) 1/2, signal transducer and activator of transcription (STAT), and suppressor of cytokine signaling (SOCS) 1 signaling-related genes. 27482661 10 57 theme expression 1696:1705 arg1 CD8α1 1664:1668 chicken CD8α1 1656:1668 chicken CD8α1 1656:1668 The results showed that chicken CD8α1 is a key regulator of the expression of genes that are associated and cooperate with transcription factors in the major histocompatibility complex class I and II promoter regions and activates Janus kinase (JAK) 1/2, signal transducer and activator of transcription (STAT), and suppressor of cytokine signaling (SOCS) 1 signaling-related genes. 27482661 0 58 theme novel 46:50 arg1 variant 65:71 a novel chicken CD8α variant X1 (CD8α1) 44:82 a novel chicken CD8α variant X1 (CD8α1) 44:82 Characterization and functional analyses of a novel chicken CD8α variant X1 (CD8α1). 27482661 1 59 theme X1 271:272 arg1 gene 282:285 the CD8α X1 (CD8α1) gene 262:285 the CD8α X1 (CD8α1) gene 262:285 We provide the first description of cloning and of structural and functional analysis of a novel variant in the chicken cluster of differentiation 8 alpha (CD8a) family, termed the CD8α X1 (CD8α1) gene. 27482661 5 60 theme sequence 925:932 arg1 similarity 934:943 relatively high sequence similarity 909:943 relatively high sequence similarity 909:943 Furthermore, the alignment showed that the transmembrane regions show relatively high sequence similarity, whereas the cytoplasmic regions show relatively low similarity, indicating poor conservation. 27482661 4 61 theme chicken 680:686 arg1 sequence 694:701 the chicken CD8α1 sequence 676:701 the chicken CD8α1 sequence 676:701 In contrast, the O-linked glycosylation sites (XPXX motif) are not found in the chicken CD8α1 sequence, and the A β strand and complementarity-determining region 1 and 2 sequences are poorly conserved between chicken CD8α1 and avian CD8α. 27482661 2 62 with alignments 297:306 arg1 sequences 342:350 known CD8α and CD8β sequences 322:350 known CD8α and CD8β sequences of other species 322:367 Multiple alignments of CD8α1 with known CD8α and CD8β sequences of other species revealed relatively low conservation of AA residues involved in the specific and unique structural domains among CD8α genes. 27482661 6 63 from sequence 1182:1189 arg1 motif 1054:1058 the motif 1050:1058 the motif (CXCP) that is thought to be responsible for binding the p56 lymphocyte cell kinase subunit (p56) 1050:1156 Moreover, the motif (CXCP) that is thought to be responsible for binding the p56 lymphocyte cell kinase subunit (p56) is missing in the CD8α1 sequence. 27482661 6 63 from sequence 1182:1189 arg1 missing 1161:1167 missing 1161:1167 missing 1161:1167 Moreover, the motif (CXCP) that is thought to be responsible for binding the p56 lymphocyte cell kinase subunit (p56) is missing in the CD8α1 sequence. 27482661 6 63 from sequence 1182:1189 arg1 responsible 1089:1099 responsible 1089:1099 responsible 1089:1099 Moreover, the motif (CXCP) that is thought to be responsible for binding the p56 lymphocyte cell kinase subunit (p56) is missing in the CD8α1 sequence. 27482661 1 64 theme chicken 197:203 arg1 cluster 205:211 the chicken cluster 193:211 the chicken cluster of differentiation 8 alpha (CD8a) family, termed the CD8α X1 (CD8α1) gene 193:285 We provide the first description of cloning and of structural and functional analysis of a novel variant in the chicken cluster of differentiation 8 alpha (CD8a) family, termed the CD8α X1 (CD8α1) gene. 27482661 9 65 theme signal 1490:1495 arg1 transduction 1497:1508 signal transduction 1490:1508 signal transduction 1490:1508 Moreover, we analyzed the signal transduction and cytokine response to CD8α1 treatment to determine the specific biological functions of chicken CD8α1 in immune cells. 27482661 12 66 theme cytokines 2271:2279 arg1 expression 2220:2229 the expression 2216:2229 the expression of proinflammatory or anti-inflammatory cytokines 2216:2279 Therefore, our data indicate that CD8α1 may have immunoregulatory activity by regulating the expression of proinflammatory or anti-inflammatory cytokines via its effect on immune cells. 27482661 4 67 theme region 755:760 arg1 sequences 770:778 the A β strand and complementarity-determining region 1 and 2 sequences 708:778 the A β strand and complementarity-determining region 1 and 2 sequences 708:778 In contrast, the O-linked glycosylation sites (XPXX motif) are not found in the chicken CD8α1 sequence, and the A β strand and complementarity-determining region 1 and 2 sequences are poorly conserved between chicken CD8α1 and avian CD8α. 27482661 11 68 theme immune 2109:2114 arg1 responses 2116:2124 innate immune responses 2102:2124 proinflammatory cytokines as well as innate immune responses 2065:2124 Immune cells that express functional CD8α1 induce proinflammatory cytokines as well as innate immune responses. 27482661 10 69 theme histocompatibility 1790:1807 arg1 class 1817:1821 the major histocompatibility complex class I 1780:1823 the major histocompatibility complex class I 1780:1823 The results showed that chicken CD8α1 is a key regulator of the expression of genes that are associated and cooperate with transcription factors in the major histocompatibility complex class I and II promoter regions and activates Janus kinase (JAK) 1/2, signal transducer and activator of transcription (STAT), and suppressor of cytokine signaling (SOCS) 1 signaling-related genes. 27482661 1 70 theme structural 136:145 arg1 analysis 162:169 structural and functional analysis 136:169 structural and functional analysis of a novel variant in the chicken cluster of differentiation 8 alpha (CD8a) family, termed the CD8α X1 (CD8α1) gene 136:285 We provide the first description of cloning and of structural and functional analysis of a novel variant in the chicken cluster of differentiation 8 alpha (CD8a) family, termed the CD8α X1 (CD8α1) gene. 27482661 11 71 theme Immune 2015:2020 arg1 cells 2022:2026 Immune cells 2015:2026 Immune cells that express functional CD8α1 2015:2056 Immune cells that express functional CD8α1 induce proinflammatory cytokines as well as innate immune responses. 27482661 4 72 theme β 714:714 arg1 strand 716:721 A β strand 712:721 A β strand 712:721 In contrast, the O-linked glycosylation sites (XPXX motif) are not found in the chicken CD8α1 sequence, and the A β strand and complementarity-determining region 1 and 2 sequences are poorly conserved between chicken CD8α1 and avian CD8α. 27482661 7 73 theme protein 1274:1280 arg1 structures 1282:1291 their protein structures 1268:1291 their protein structures 1268:1291 The chicken CD8α1 genomic structure is similar to that of chicken CD8α, but their protein structures differ. 27482661 11 74 theme functional 2041:2050 arg1 CD8α1 2052:2056 functional CD8α1 2041:2056 functional CD8α1 2041:2056 Immune cells that express functional CD8α1 induce proinflammatory cytokines as well as innate immune responses. 27482661 6 75 theme cell 1132:1135 arg1 p56 1153:1155 p56 1153:1155 p56 1153:1155 Moreover, the motif (CXCP) that is thought to be responsible for binding the p56 lymphocyte cell kinase subunit (p56) is missing in the CD8α1 sequence. 27482661 6 75 theme cell 1132:1135 arg1 subunit 1144:1150 the p56 lymphocyte cell kinase subunit 1113:1150 the p56 lymphocyte cell kinase subunit (p56) 1113:1156 Moreover, the motif (CXCP) that is thought to be responsible for binding the p56 lymphocyte cell kinase subunit (p56) is missing in the CD8α1 sequence. 27482661 1 76 theme functional 151:160 arg1 analysis 162:169 structural and functional analysis 136:169 structural and functional analysis of a novel variant in the chicken cluster of differentiation 8 alpha (CD8a) family, termed the CD8α X1 (CD8α1) gene 136:285 We provide the first description of cloning and of structural and functional analysis of a novel variant in the chicken cluster of differentiation 8 alpha (CD8a) family, termed the CD8α X1 (CD8α1) gene. 27482661 10 77 theme SOCS 1982:1985 arg1 activator 1909:1917 activator 1909:1917 activator 1909:1917 The results showed that chicken CD8α1 is a key regulator of the expression of genes that are associated and cooperate with transcription factors in the major histocompatibility complex class I and II promoter regions and activates Janus kinase (JAK) 1/2, signal transducer and activator of transcription (STAT), and suppressor of cytokine signaling (SOCS) 1 signaling-related genes. 27482661 10 77 theme SOCS 1982:1985 arg1 suppressor 1948:1957 suppressor 1948:1957 suppressor of cytokine signaling (SOCS) 1 1948:1988 The results showed that chicken CD8α1 is a key regulator of the expression of genes that are associated and cooperate with transcription factors in the major histocompatibility complex class I and II promoter regions and activates Janus kinase (JAK) 1/2, signal transducer and activator of transcription (STAT), and suppressor of cytokine signaling (SOCS) 1 signaling-related genes. 27482661 10 77 theme SOCS 1982:1985 arg1 transducer 1894:1903 signal transducer 1887:1903 signal transducer 1887:1903 The results showed that chicken CD8α1 is a key regulator of the expression of genes that are associated and cooperate with transcription factors in the major histocompatibility complex class I and II promoter regions and activates Janus kinase (JAK) 1/2, signal transducer and activator of transcription (STAT), and suppressor of cytokine signaling (SOCS) 1 signaling-related genes. 27482661 10 77 theme SOCS 1982:1985 arg1 JAK 1877:1879 Janus kinase (JAK) 1/2 1863:1884 Janus kinase (JAK) 1/2 1863:1884 The results showed that chicken CD8α1 is a key regulator of the expression of genes that are associated and cooperate with transcription factors in the major histocompatibility complex class I and II promoter regions and activates Janus kinase (JAK) 1/2, signal transducer and activator of transcription (STAT), and suppressor of cytokine signaling (SOCS) 1 signaling-related genes. 27482661 10 77 theme SOCS 1982:1985 arg1 STAT 1937:1940 STAT 1937:1940 STAT 1937:1940 The results showed that chicken CD8α1 is a key regulator of the expression of genes that are associated and cooperate with transcription factors in the major histocompatibility complex class I and II promoter regions and activates Janus kinase (JAK) 1/2, signal transducer and activator of transcription (STAT), and suppressor of cytokine signaling (SOCS) 1 signaling-related genes. 27482661 8 78 theme Phylogenetic 1301:1312 arg1 analysis 1314:1321 Phylogenetic analysis 1301:1321 Phylogenetic analysis 1301:1321 Phylogenetic analysis showed that chicken CD8α1 grouped with known avian CD8α sequences but was somewhat distantly related to the CD8α molecules of other species. 27482661 10 79 theme signaling 1971:1979 arg1 SOCS 1982:1985 cytokine signaling (SOCS) 1 1962:1988 cytokine signaling (SOCS) 1 1962:1988 The results showed that chicken CD8α1 is a key regulator of the expression of genes that are associated and cooperate with transcription factors in the major histocompatibility complex class I and II promoter regions and activates Janus kinase (JAK) 1/2, signal transducer and activator of transcription (STAT), and suppressor of cytokine signaling (SOCS) 1 signaling-related genes. 27482661 4 80 gly glycosylation 626:638 arg2 sites 640:644 the O-linked glycosylation sites 613:644 the O-linked glycosylation sites (XPXX motif) 613:657 In contrast, the O-linked glycosylation sites (XPXX motif) are not found in the chicken CD8α1 sequence, and the A β strand and complementarity-determining region 1 and 2 sequences are poorly conserved between chicken CD8α1 and avian CD8α. 27482661 4 80 gly glycosylation 626:638 arg2 motif 652:656 XPXX motif 647:656 XPXX motif 647:656 In contrast, the O-linked glycosylation sites (XPXX motif) are not found in the chicken CD8α1 sequence, and the A β strand and complementarity-determining region 1 and 2 sequences are poorly conserved between chicken CD8α1 and avian CD8α. 27482661 1 81 theme novel 176:180 arg1 variant 182:188 a novel variant 174:188 a novel variant in the chicken cluster of differentiation 8 alpha (CD8a) family, termed the CD8α X1 (CD8α1) gene 174:285 We provide the first description of cloning and of structural and functional analysis of a novel variant in the chicken cluster of differentiation 8 alpha (CD8a) family, termed the CD8α X1 (CD8α1) gene. 27482661 2 82 theme structural 457:466 arg1 domains 468:474 the specific and unique structural domains 433:474 the specific and unique structural domains 433:474 Multiple alignments of CD8α1 with known CD8α and CD8β sequences of other species revealed relatively low conservation of AA residues involved in the specific and unique structural domains among CD8α genes. 27482661 6 83 theme CD8α1 1176:1180 arg1 sequence 1182:1189 the CD8α1 sequence 1172:1189 the CD8α1 sequence 1172:1189 Moreover, the motif (CXCP) that is thought to be responsible for binding the p56 lymphocyte cell kinase subunit (p56) is missing in the CD8α1 sequence. 27482661 1 84 from variant 182:188 arg1 cluster 205:211 the chicken cluster 193:211 the chicken cluster of differentiation 8 alpha (CD8a) family, termed the CD8α X1 (CD8α1) gene 193:285 We provide the first description of cloning and of structural and functional analysis of a novel variant in the chicken cluster of differentiation 8 alpha (CD8a) family, termed the CD8α X1 (CD8α1) gene. 27482661 2 85 theme CD8α 482:485 arg1 genes 487:491 CD8α genes 482:491 CD8α genes 482:491 Multiple alignments of CD8α1 with known CD8α and CD8β sequences of other species revealed relatively low conservation of AA residues involved in the specific and unique structural domains among CD8α genes. 27482661 10 86 theme promoter 1832:1839 arg1 regions 1841:1847 II promoter regions 1829:1847 II promoter regions 1829:1847 The results showed that chicken CD8α1 is a key regulator of the expression of genes that are associated and cooperate with transcription factors in the major histocompatibility complex class I and II promoter regions and activates Janus kinase (JAK) 1/2, signal transducer and activator of transcription (STAT), and suppressor of cytokine signaling (SOCS) 1 signaling-related genes. 27482661 1 87 theme first 100:104 arg1 description 106:116 the first description 96:116 the first description of cloning and of structural and functional analysis of a novel variant in the chicken cluster of differentiation 8 alpha (CD8a) family, termed the CD8α X1 (CD8α1) gene 96:285 We provide the first description of cloning and of structural and functional analysis of a novel variant in the chicken cluster of differentiation 8 alpha (CD8a) family, termed the CD8α X1 (CD8α1) gene. 27482661 9 88 theme CD8α1 1609:1613 arg1 functions 1588:1596 the specific biological functions 1564:1596 the specific biological functions of chicken CD8α1 in immune cells 1564:1629 Moreover, we analyzed the signal transduction and cytokine response to CD8α1 treatment to determine the specific biological functions of chicken CD8α1 in immune cells. 27482661 10 89 dep JAK 1877:1879 arg1 genes 2008:2012 signaling-related genes 1990:2012 signaling-related genes 1990:2012 The results showed that chicken CD8α1 is a key regulator of the expression of genes that are associated and cooperate with transcription factors in the major histocompatibility complex class I and II promoter regions and activates Janus kinase (JAK) 1/2, signal transducer and activator of transcription (STAT), and suppressor of cytokine signaling (SOCS) 1 signaling-related genes. 27482661 4 90 theme glycosylation 626:638 arg1 motif 652:656 XPXX motif 647:656 XPXX motif 647:656 In contrast, the O-linked glycosylation sites (XPXX motif) are not found in the chicken CD8α1 sequence, and the A β strand and complementarity-determining region 1 and 2 sequences are poorly conserved between chicken CD8α1 and avian CD8α. 27482661 4 90 theme glycosylation 626:638 arg1 sites 640:644 the O-linked glycosylation sites 613:644 the O-linked glycosylation sites (XPXX motif) 613:657 In contrast, the O-linked glycosylation sites (XPXX motif) are not found in the chicken CD8α1 sequence, and the A β strand and complementarity-determining region 1 and 2 sequences are poorly conserved between chicken CD8α1 and avian CD8α. 27482661 0 91 theme variant 65:71 arg1 Characterization 0:15 Characterization 0:15 Characterization 0:15 Characterization and functional analyses of a novel chicken CD8α variant X1 (CD8α1). 27482661 0 91 theme variant 65:71 arg1 analyses 32:39 functional analyses 21:39 functional analyses 21:39 Characterization and functional analyses of a novel chicken CD8α variant X1 (CD8α1). 27482661 1 92 from analysis 162:169 arg1 cluster 205:211 the chicken cluster 193:211 the chicken cluster of differentiation 8 alpha (CD8a) family, termed the CD8α X1 (CD8α1) gene 193:285 We provide the first description of cloning and of structural and functional analysis of a novel variant in the chicken cluster of differentiation 8 alpha (CD8a) family, termed the CD8α X1 (CD8α1) gene. 27482661 9 93 from functions 1588:1596 arg1 cells 1625:1629 immune cells 1618:1629 immune cells 1618:1629 Moreover, we analyzed the signal transduction and cytokine response to CD8α1 treatment to determine the specific biological functions of chicken CD8α1 in immune cells. 27482661 9 94 theme immune 1618:1623 arg1 cells 1625:1629 immune cells 1618:1629 immune cells 1618:1629 Moreover, we analyzed the signal transduction and cytokine response to CD8α1 treatment to determine the specific biological functions of chicken CD8α1 in immune cells. 27482661 8 95 theme known 1362:1366 arg1 sequences 1379:1387 known avian CD8α sequences 1362:1387 known avian CD8α sequences 1362:1387 Phylogenetic analysis showed that chicken CD8α1 grouped with known avian CD8α sequences but was somewhat distantly related to the CD8α molecules of other species. 27482661 7 96 theme genomic 1210:1216 arg1 structure 1218:1226 The chicken CD8α1 genomic structure 1192:1226 The chicken CD8α1 genomic structure 1192:1226 The chicken CD8α1 genomic structure is similar to that of chicken CD8α, but their protein structures differ. 27482661 7 96 theme genomic 1210:1216 arg1 similar 1231:1237 similar 1231:1237 similar 1231:1237 The chicken CD8α1 genomic structure is similar to that of chicken CD8α, but their protein structures differ. 27482661 10 97 theme Janus 1863:1867 arg1 JAK 1877:1879 Janus kinase (JAK) 1/2 1863:1884 Janus kinase (JAK) 1/2 1863:1884 The results showed that chicken CD8α1 is a key regulator of the expression of genes that are associated and cooperate with transcription factors in the major histocompatibility complex class I and II promoter regions and activates Janus kinase (JAK) 1/2, signal transducer and activator of transcription (STAT), and suppressor of cytokine signaling (SOCS) 1 signaling-related genes. 27482661 2 98 theme AA 409:410 arg1 residues 412:419 AA residues 409:419 AA residues involved in the specific and unique structural domains 409:474 Multiple alignments of CD8α1 with known CD8α and CD8β sequences of other species revealed relatively low conservation of AA residues involved in the specific and unique structural domains among CD8α genes. 27482661 8 99 theme CD8α 1374:1377 arg1 sequences 1379:1387 known avian CD8α sequences 1362:1387 known avian CD8α sequences 1362:1387 Phylogenetic analysis showed that chicken CD8α1 grouped with known avian CD8α sequences but was somewhat distantly related to the CD8α molecules of other species. 27482661 4 100 theme avian 827:831 arg1 CD8α 833:836 avian CD8α 827:836 avian CD8α 827:836 In contrast, the O-linked glycosylation sites (XPXX motif) are not found in the chicken CD8α1 sequence, and the A β strand and complementarity-determining region 1 and 2 sequences are poorly conserved between chicken CD8α1 and avian CD8α. 27482661 8 101 theme species 1455:1461 arg1 molecules 1436:1444 the CD8α molecules 1427:1444 the CD8α molecules of other species 1427:1461 Phylogenetic analysis showed that chicken CD8α1 grouped with known avian CD8α sequences but was somewhat distantly related to the CD8α molecules of other species. 27482661 11 102 theme proinflammatory 2065:2079 arg1 cytokines 2081:2089 proinflammatory cytokines 2065:2089 proinflammatory cytokines as well as innate immune responses 2065:2124 Immune cells that express functional CD8α1 induce proinflammatory cytokines as well as innate immune responses. 27482661 2 103 theme species 361:367 arg1 sequences 342:350 known CD8α and CD8β sequences 322:350 known CD8α and CD8β sequences of other species 322:367 Multiple alignments of CD8α1 with known CD8α and CD8β sequences of other species revealed relatively low conservation of AA residues involved in the specific and unique structural domains among CD8α genes. 27482661 12 104 theme immune 2299:2304 arg1 cells 2306:2310 immune cells 2299:2310 immune cells 2299:2310 Therefore, our data indicate that CD8α1 may have immunoregulatory activity by regulating the expression of proinflammatory or anti-inflammatory cytokines via its effect on immune cells. 27482661 9 105 dep transduction 1497:1508 arg1 the 1486:1488 the 1486:1488 the 1486:1488 Moreover, we analyzed the signal transduction and cytokine response to CD8α1 treatment to determine the specific biological functions of chicken CD8α1 in immune cells. 27482661 1 106 theme CD8a 241:244 arg1 family 247:252 differentiation 8 alpha (CD8a) family 216:252 differentiation 8 alpha (CD8a) family 216:252 We provide the first description of cloning and of structural and functional analysis of a novel variant in the chicken cluster of differentiation 8 alpha (CD8a) family, termed the CD8α X1 (CD8α1) gene. 27482661 0 107 dep variant 65:71 arg1 X1 73:74 X1 73:74 a novel chicken CD8α variant X1 (CD8α1) 44:82 Characterization and functional analyses of a novel chicken CD8α variant X1 (CD8α1). 27482661 0 107 dep variant 65:71 arg1 CD8α1 77:81 CD8α1 77:81 CD8α1 77:81 Characterization and functional analyses of a novel chicken CD8α variant X1 (CD8α1). 27482661 4 108 located found 667:671 arg1 contrast 603:610 contrast 603:610 contrast 603:610 In contrast, the O-linked glycosylation sites (XPXX motif) are not found in the chicken CD8α1 sequence, and the A β strand and complementarity-determining region 1 and 2 sequences are poorly conserved between chicken CD8α1 and avian CD8α. 27482661 4 108 located found 667:671 arg2 sites 640:644 the O-linked glycosylation sites 613:644 the O-linked glycosylation sites (XPXX motif) 613:657 In contrast, the O-linked glycosylation sites (XPXX motif) are not found in the chicken CD8α1 sequence, and the A β strand and complementarity-determining region 1 and 2 sequences are poorly conserved between chicken CD8α1 and avian CD8α. 27482661 4 108 located found 667:671 arg1 sequence 694:701 the chicken CD8α1 sequence 676:701 the chicken CD8α1 sequence 676:701 In contrast, the O-linked glycosylation sites (XPXX motif) are not found in the chicken CD8α1 sequence, and the A β strand and complementarity-determining region 1 and 2 sequences are poorly conserved between chicken CD8α1 and avian CD8α. 27482661 4 108 located found 667:671 arg2 motif 652:656 XPXX motif 647:656 XPXX motif 647:656 In contrast, the O-linked glycosylation sites (XPXX motif) are not found in the chicken CD8α1 sequence, and the A β strand and complementarity-determining region 1 and 2 sequences are poorly conserved between chicken CD8α1 and avian CD8α. 27482661 2 109 theme CD8β 337:340 arg1 sequences 342:350 known CD8α and CD8β sequences 322:350 known CD8α and CD8β sequences of other species 322:367 Multiple alignments of CD8α1 with known CD8α and CD8β sequences of other species revealed relatively low conservation of AA residues involved in the specific and unique structural domains among CD8α genes. 27482661 1 110 theme family 247:252 arg1 cluster 205:211 the chicken cluster 193:211 the chicken cluster of differentiation 8 alpha (CD8a) family, termed the CD8α X1 (CD8α1) gene 193:285 We provide the first description of cloning and of structural and functional analysis of a novel variant in the chicken cluster of differentiation 8 alpha (CD8a) family, termed the CD8α X1 (CD8α1) gene. 27482661 2 111 theme CD8α 328:331 arg1 sequences 342:350 known CD8α and CD8β sequences 322:350 known CD8α and CD8β sequences of other species 322:367 Multiple alignments of CD8α1 with known CD8α and CD8β sequences of other species revealed relatively low conservation of AA residues involved in the specific and unique structural domains among CD8α genes. 27482661 0 112 theme chicken 52:58 arg1 variant 65:71 a novel chicken CD8α variant X1 (CD8α1) 44:82 a novel chicken CD8α variant X1 (CD8α1) 44:82 Characterization and functional analyses of a novel chicken CD8α variant X1 (CD8α1). 27482661 6 113 from missing 1161:1167 arg1 sequence 1182:1189 the CD8α1 sequence 1172:1189 the CD8α1 sequence 1172:1189 Moreover, the motif (CXCP) that is thought to be responsible for binding the p56 lymphocyte cell kinase subunit (p56) is missing in the CD8α1 sequence. 27482661 5 114 theme high 920:923 arg1 similarity 934:943 relatively high sequence similarity 909:943 relatively high sequence similarity 909:943 Furthermore, the alignment showed that the transmembrane regions show relatively high sequence similarity, whereas the cytoplasmic regions show relatively low similarity, indicating poor conservation. 27482661 9 115 theme biological 1577:1586 arg1 functions 1588:1596 the specific biological functions 1564:1596 the specific biological functions of chicken CD8α1 in immune cells 1564:1629 Moreover, we analyzed the signal transduction and cytokine response to CD8α1 treatment to determine the specific biological functions of chicken CD8α1 in immune cells. 27482661 8 116 theme other 1449:1453 arg1 species 1455:1461 other species 1449:1461 other species 1449:1461 Phylogenetic analysis showed that chicken CD8α1 grouped with known avian CD8α sequences but was somewhat distantly related to the CD8α molecules of other species. 27482661 1 117 theme CD8α 266:269 arg1 gene 282:285 the CD8α X1 (CD8α1) gene 262:285 the CD8α X1 (CD8α1) gene 262:285 We provide the first description of cloning and of structural and functional analysis of a novel variant in the chicken cluster of differentiation 8 alpha (CD8a) family, termed the CD8α X1 (CD8α1) gene. 27482661 12 118 theme proinflammatory 2234:2248 arg1 cytokines 2271:2279 proinflammatory or anti-inflammatory cytokines 2234:2279 cytokines 2271:2279 Therefore, our data indicate that CD8α1 may have immunoregulatory activity by regulating the expression of proinflammatory or anti-inflammatory cytokines via its effect on immune cells. 27482661 3 119 theme V 576:576 arg1 domain 578:583 the V domain 572:583 the V domain 572:583 For example, cysteine residues that are involved in disulfide bonding to form the V domain are conserved. 27482661 5 120 theme transmembrane 882:894 arg1 regions 896:902 the transmembrane regions 878:902 the transmembrane regions 878:902 Furthermore, the alignment showed that the transmembrane regions show relatively high sequence similarity, whereas the cytoplasmic regions show relatively low similarity, indicating poor conservation. 27482661 12 121 theme anti-inflammatory 2253:2269 arg1 cytokines 2271:2279 proinflammatory or anti-inflammatory cytokines 2234:2279 cytokines 2271:2279 Therefore, our data indicate that CD8α1 may have immunoregulatory activity by regulating the expression of proinflammatory or anti-inflammatory cytokines via its effect on immune cells. 27482661 4 122 theme CD8α1 688:692 arg1 sequence 694:701 the chicken CD8α1 sequence 676:701 the chicken CD8α1 sequence 676:701 In contrast, the O-linked glycosylation sites (XPXX motif) are not found in the chicken CD8α1 sequence, and the A β strand and complementarity-determining region 1 and 2 sequences are poorly conserved between chicken CD8α1 and avian CD8α. 27482661 2 123 theme Multiple 288:295 arg1 alignments 297:306 Multiple alignments 288:306 Multiple alignments of CD8α1 with known CD8α and CD8β sequences of other species 288:367 Multiple alignments of CD8α1 with known CD8α and CD8β sequences of other species revealed relatively low conservation of AA residues involved in the specific and unique structural domains among CD8α genes. 27290989 0 0 theme nuclear 97:103 arg1 translocation 105:117 nuclear translocation 97:117 nuclear translocation of NF-κB 97:126 Mechanistic insights of O-GlcNAcylation that promote progression of cholangiocarcinoma cells via nuclear translocation of NF-κB. 27290989 10 1 theme CCA 1658:1660 arg1 treatment 1634:1642 treatment 1634:1642 treatment of metastatic CCA 1634:1660 This information indicates the significance of O-GlcNAcylation in controlling the metastatic ability of CCA cells, hence, O-GlcNAcylation and its products may be new targets for treatment of metastatic CCA. 27290989 7 2 theme upstream 1098:1105 arg1 cascade 1117:1123 the upstream signaling cascade 1094:1123 the upstream signaling cascade of MMP activation 1094:1141 O-GlcNAcylation and nuclear translocation of NF-κB, the upstream signaling cascade of MMP activation were shown to be important for MMP activation. 27290989 7 2 theme upstream 1098:1105 arg1 NF-κB 1087:1091 NF-κB 1087:1091 NF-κB 1087:1091 O-GlcNAcylation and nuclear translocation of NF-κB, the upstream signaling cascade of MMP activation were shown to be important for MMP activation. 27290989 10 3 theme new 1618:1620 arg1 targets 1622:1628 new targets 1618:1628 new targets for treatment of metastatic CCA 1618:1660 This information indicates the significance of O-GlcNAcylation in controlling the metastatic ability of CCA cells, hence, O-GlcNAcylation and its products may be new targets for treatment of metastatic CCA. 27290989 7 4 theme signaling 1107:1115 arg1 cascade 1117:1123 the upstream signaling cascade 1094:1123 the upstream signaling cascade of MMP activation 1094:1141 O-GlcNAcylation and nuclear translocation of NF-κB, the upstream signaling cascade of MMP activation were shown to be important for MMP activation. 27290989 7 4 theme signaling 1107:1115 arg1 NF-κB 1087:1091 NF-κB 1087:1091 NF-κB 1087:1091 O-GlcNAcylation and nuclear translocation of NF-κB, the upstream signaling cascade of MMP activation were shown to be important for MMP activation. 27290989 1 5 theme O-GlcNAc 264:271 arg1 transferase 273:283 O-GlcNAc transferase 264:283 O-GlcNAc transferase (OGT) 264:289 O-GlcNAcylation, an O-linked protein glycosylation with a single molecule of N-acetylglucosamine (GlcNAc), is reversibly controlled by O-GlcNAc transferase (OGT) and N-acetyl D-glucosaminidase (OGA). 27290989 1 5 theme O-GlcNAc 264:271 arg1 OGT 286:288 OGT 286:288 OGT 286:288 O-GlcNAcylation, an O-linked protein glycosylation with a single molecule of N-acetylglucosamine (GlcNAc), is reversibly controlled by O-GlcNAc transferase (OGT) and N-acetyl D-glucosaminidase (OGA). 27290989 10 6 theme metastatic 1647:1656 arg1 CCA 1658:1660 metastatic CCA 1647:1660 metastatic CCA 1647:1660 This information indicates the significance of O-GlcNAcylation in controlling the metastatic ability of CCA cells, hence, O-GlcNAcylation and its products may be new targets for treatment of metastatic CCA. 27290989 6 7 theme NF-κB 950:954 arg1 translocation 933:945 the nuclear translocation 921:945 the nuclear translocation of NF-κB and Akt-phosphorylation together with expression of matrix-metalloproteinases (MMPs) 921:1039 Manipulating levels of O-GlcNAcylation did affect the nuclear translocation of NF-κB and Akt-phosphorylation together with expression of matrix-metalloproteinases (MMPs). 27290989 8 8 with elevation 1223:1231 arg1 O-GlcNAcylation 1284:1298 increased cellular O-GlcNAcylation 1265:1298 increased cellular O-GlcNAcylation 1265:1298 Immunoprecipitation revealed the elevation of O-GlcNAc-modified NF-κB with increased cellular O-GlcNAcylation. 27290989 2 9 theme important 369:377 arg1 role 379:382 an important role 366:382 an important role 366:382 Aberrant O-GlcNAcylation contributes an important role in initiation and progression of many human cancers. 27290989 8 10 theme O-GlcNAc-modified 1236:1252 arg1 NF-κB 1254:1258 O-GlcNAc-modified NF-κB 1236:1258 O-GlcNAc-modified NF-κB 1236:1258 Immunoprecipitation revealed the elevation of O-GlcNAc-modified NF-κB with increased cellular O-GlcNAcylation. 27290989 3 11 from Elevation 437:445 arg1 tissues 475:481 tumor tissues 469:481 tumor tissues 469:481 Elevation of O-GlcNAcylation in tumor tissues and poor prognosis of cholangiocarcinoma (CCA) patients have been reported. 27290989 10 12 theme cells 1564:1568 arg1 ability 1549:1555 the metastatic ability 1534:1555 the metastatic ability of CCA cells 1534:1568 This information indicates the significance of O-GlcNAcylation in controlling the metastatic ability of CCA cells, hence, O-GlcNAcylation and its products may be new targets for treatment of metastatic CCA. 27290989 3 13 from patients 530:537 arg1 tissues 475:481 tumor tissues 469:481 tumor tissues 469:481 Elevation of O-GlcNAcylation in tumor tissues and poor prognosis of cholangiocarcinoma (CCA) patients have been reported. 27290989 1 14 with glycosylation 166:178 arg1 molecule 194:201 a single molecule 185:201 a single molecule of N-acetylglucosamine (GlcNAc) 185:233 O-GlcNAcylation, an O-linked protein glycosylation with a single molecule of N-acetylglucosamine (GlcNAc), is reversibly controlled by O-GlcNAc transferase (OGT) and N-acetyl D-glucosaminidase (OGA). 27290989 6 15 theme O-GlcNAcylation 894:908 arg1 levels 884:889 Manipulating levels 871:889 Manipulating levels of O-GlcNAcylation 871:908 Manipulating levels of O-GlcNAcylation did affect the nuclear translocation of NF-κB and Akt-phosphorylation together with expression of matrix-metalloproteinases (MMPs). 27290989 2 16 theme Aberrant 329:336 arg1 O-GlcNAcylation 338:352 Aberrant O-GlcNAcylation 329:352 Aberrant O-GlcNAcylation 329:352 Aberrant O-GlcNAcylation contributes an important role in initiation and progression of many human cancers. 27290989 6 17 theme nuclear 925:931 arg1 translocation 933:945 the nuclear translocation 921:945 the nuclear translocation of NF-κB and Akt-phosphorylation together with expression of matrix-metalloproteinases (MMPs) 921:1039 Manipulating levels of O-GlcNAcylation did affect the nuclear translocation of NF-κB and Akt-phosphorylation together with expression of matrix-metalloproteinases (MMPs). 27290989 1 18 theme single 187:192 arg1 molecule 194:201 a single molecule 185:201 a single molecule of N-acetylglucosamine (GlcNAc) 185:233 O-GlcNAcylation, an O-linked protein glycosylation with a single molecule of N-acetylglucosamine (GlcNAc), is reversibly controlled by O-GlcNAc transferase (OGT) and N-acetyl D-glucosaminidase (OGA). 27290989 0 19 theme NF-κB 122:126 arg1 translocation 105:117 nuclear translocation 97:117 nuclear translocation of NF-κB 97:126 Mechanistic insights of O-GlcNAcylation that promote progression of cholangiocarcinoma cells via nuclear translocation of NF-κB. 27290989 9 20 theme nuclear 1424:1430 arg1 translocation 1432:1444 nuclear translocation 1424:1444 nuclear translocation 1424:1444 Involvement of O-GlcNAcylation in MMP-mediated migration and invasion of CCA cells was shown to be via O-GlcNAcylation and nuclear translocation of NF-κB. 27290989 4 21 theme O-GlcNAcylation 586:600 arg1 role 578:581 the role 574:581 the role of O-GlcNAcylation in promoting tumor progression 574:631 In this study, the role of O-GlcNAcylation in promoting tumor progression was further investigated in CCA cell lines. 27290989 5 22 theme treated 829:835 arg1 cells 837:841 siOGA treated cells 823:841 siOGA treated cells 823:841 Suppression of O-GlcNAcylation using small interfering RNAs of OGT (siOGT) significantly reduced cell migration and invasion of CCA cells whereas siOGA treated cells exhibited opposite effects. 27290989 3 23 theme tumor 469:473 arg1 tissues 475:481 tumor tissues 469:481 tumor tissues 469:481 Elevation of O-GlcNAcylation in tumor tissues and poor prognosis of cholangiocarcinoma (CCA) patients have been reported. 27290989 5 24 theme siOGA 823:827 arg1 cells 837:841 siOGA treated cells 823:841 siOGA treated cells 823:841 Suppression of O-GlcNAcylation using small interfering RNAs of OGT (siOGT) significantly reduced cell migration and invasion of CCA cells whereas siOGA treated cells exhibited opposite effects. 27290989 5 25 theme cell 774:777 arg1 migration 779:787 cell migration 774:787 cell migration 774:787 Suppression of O-GlcNAcylation using small interfering RNAs of OGT (siOGT) significantly reduced cell migration and invasion of CCA cells whereas siOGA treated cells exhibited opposite effects. 27290989 0 26 theme Mechanistic 0:10 arg1 insights 12:19 Mechanistic insights 0:19 Mechanistic insights of O-GlcNAcylation that promote progression of cholangiocarcinoma cells via nuclear translocation of NF-κB 0:126 Mechanistic insights of O-GlcNAcylation that promote progression of cholangiocarcinoma cells via nuclear translocation of NF-κB. 27290989 10 27 theme CCA 1560:1562 arg1 cells 1564:1568 CCA cells 1560:1568 CCA cells 1560:1568 This information indicates the significance of O-GlcNAcylation in controlling the metastatic ability of CCA cells, hence, O-GlcNAcylation and its products may be new targets for treatment of metastatic CCA. 27290989 9 28 theme O-GlcNAcylation 1316:1330 arg1 Involvement 1301:1311 Involvement 1301:1311 Involvement of O-GlcNAcylation in MMP-mediated migration and invasion of CCA cells 1301:1382 Involvement of O-GlcNAcylation in MMP-mediated migration and invasion of CCA cells was shown to be via O-GlcNAcylation and nuclear translocation of NF-κB. 27290989 10 29 theme O-GlcNAcylation 1503:1517 arg1 significance 1487:1498 the significance 1483:1498 the significance of O-GlcNAcylation in controlling the metastatic ability of CCA cells 1483:1568 This information indicates the significance of O-GlcNAcylation in controlling the metastatic ability of CCA cells, hence, O-GlcNAcylation and its products may be new targets for treatment of metastatic CCA. 27290989 1 30 theme N-acetylglucosamine 206:224 arg1 molecule 194:201 a single molecule 185:201 a single molecule of N-acetylglucosamine (GlcNAc) 185:233 O-GlcNAcylation, an O-linked protein glycosylation with a single molecule of N-acetylglucosamine (GlcNAc), is reversibly controlled by O-GlcNAc transferase (OGT) and N-acetyl D-glucosaminidase (OGA). 27290989 0 31 theme O-GlcNAcylation 24:38 arg1 insights 12:19 Mechanistic insights 0:19 Mechanistic insights of O-GlcNAcylation that promote progression of cholangiocarcinoma cells via nuclear translocation of NF-κB 0:126 Mechanistic insights of O-GlcNAcylation that promote progression of cholangiocarcinoma cells via nuclear translocation of NF-κB. 27290989 8 32 theme NF-κB 1254:1258 arg1 elevation 1223:1231 the elevation 1219:1231 the elevation of O-GlcNAc-modified NF-κB with increased cellular O-GlcNAcylation 1219:1298 Immunoprecipitation revealed the elevation of O-GlcNAc-modified NF-κB with increased cellular O-GlcNAcylation. 27290989 7 33 theme activation 1132:1141 arg1 cascade 1117:1123 the upstream signaling cascade 1094:1123 the upstream signaling cascade of MMP activation 1094:1141 O-GlcNAcylation and nuclear translocation of NF-κB, the upstream signaling cascade of MMP activation were shown to be important for MMP activation. 27290989 7 33 theme activation 1132:1141 arg1 NF-κB 1087:1091 NF-κB 1087:1091 NF-κB 1087:1091 O-GlcNAcylation and nuclear translocation of NF-κB, the upstream signaling cascade of MMP activation were shown to be important for MMP activation. 27290989 3 34 theme poor 487:490 arg1 CCA 525:527 CCA 525:527 CCA 525:527 Elevation of O-GlcNAcylation in tumor tissues and poor prognosis of cholangiocarcinoma (CCA) patients have been reported. 27290989 3 34 theme poor 487:490 arg1 prognosis 492:500 poor prognosis 487:500 poor prognosis of cholangiocarcinoma (CCA) patients 487:537 Elevation of O-GlcNAcylation in tumor tissues and poor prognosis of cholangiocarcinoma (CCA) patients have been reported. 27290989 7 35 theme nuclear 1062:1068 arg1 translocation 1070:1082 nuclear translocation 1062:1082 nuclear translocation 1062:1082 O-GlcNAcylation and nuclear translocation of NF-κB, the upstream signaling cascade of MMP activation were shown to be important for MMP activation. 27290989 1 36 theme N-acetyl 295:302 arg1 OGA 323:325 OGA 323:325 OGA 323:325 O-GlcNAcylation, an O-linked protein glycosylation with a single molecule of N-acetylglucosamine (GlcNAc), is reversibly controlled by O-GlcNAc transferase (OGT) and N-acetyl D-glucosaminidase (OGA). 27290989 1 36 theme N-acetyl 295:302 arg1 D-glucosaminidase 304:320 N-acetyl D-glucosaminidase 295:320 N-acetyl D-glucosaminidase (OGA) 295:326 O-GlcNAcylation, an O-linked protein glycosylation with a single molecule of N-acetylglucosamine (GlcNAc), is reversibly controlled by O-GlcNAc transferase (OGT) and N-acetyl D-glucosaminidase (OGA). 27290989 9 37 theme MMP-mediated 1335:1346 arg1 migration 1348:1356 MMP-mediated migration 1335:1356 MMP-mediated migration 1335:1356 Involvement of O-GlcNAcylation in MMP-mediated migration and invasion of CCA cells was shown to be via O-GlcNAcylation and nuclear translocation of NF-κB. 27290989 3 38 theme prognosis 492:500 arg1 patients 530:537 poor prognosis of cholangiocarcinoma (CCA) patients 487:537 poor prognosis of cholangiocarcinoma (CCA) patients 487:537 Elevation of O-GlcNAcylation in tumor tissues and poor prognosis of cholangiocarcinoma (CCA) patients have been reported. 27290989 6 39 theme matrix-metalloproteinases 1008:1032 arg1 expression 994:1003 expression 994:1003 expression of matrix-metalloproteinases (MMPs) 994:1039 Manipulating levels of O-GlcNAcylation did affect the nuclear translocation of NF-κB and Akt-phosphorylation together with expression of matrix-metalloproteinases (MMPs). 27290989 5 40 theme OGT 740:742 arg1 RNAs 732:735 small interfering RNAs 714:735 small interfering RNAs of OGT (siOGT) 714:750 Suppression of O-GlcNAcylation using small interfering RNAs of OGT (siOGT) significantly reduced cell migration and invasion of CCA cells whereas siOGA treated cells exhibited opposite effects. 27290989 4 41 theme cell 665:668 arg1 lines 670:674 CCA cell lines 661:674 CCA cell lines 661:674 In this study, the role of O-GlcNAcylation in promoting tumor progression was further investigated in CCA cell lines. 27290989 3 42 theme O-GlcNAcylation 450:464 arg1 patients 530:537 poor prognosis of cholangiocarcinoma (CCA) patients 487:537 poor prognosis of cholangiocarcinoma (CCA) patients 487:537 Elevation of O-GlcNAcylation in tumor tissues and poor prognosis of cholangiocarcinoma (CCA) patients have been reported. 27290989 3 42 theme O-GlcNAcylation 450:464 arg1 Elevation 437:445 Elevation 437:445 Elevation of O-GlcNAcylation in tumor tissues 437:481 Elevation of O-GlcNAcylation in tumor tissues and poor prognosis of cholangiocarcinoma (CCA) patients have been reported. 27290989 2 43 theme cancers 428:434 arg1 progression 402:412 progression 402:412 progression 402:412 Aberrant O-GlcNAcylation contributes an important role in initiation and progression of many human cancers. 27290989 2 43 theme cancers 428:434 arg1 initiation 387:396 initiation 387:396 initiation 387:396 Aberrant O-GlcNAcylation contributes an important role in initiation and progression of many human cancers. 27290989 2 44 theme many 417:420 arg1 cancers 428:434 many human cancers 417:434 many human cancers 417:434 Aberrant O-GlcNAcylation contributes an important role in initiation and progression of many human cancers. 27290989 5 45 theme CCA 805:807 arg1 cells 809:813 CCA cells 805:813 CCA cells 805:813 Suppression of O-GlcNAcylation using small interfering RNAs of OGT (siOGT) significantly reduced cell migration and invasion of CCA cells whereas siOGA treated cells exhibited opposite effects. 27290989 7 46 theme NF-κB 1087:1091 arg1 O-GlcNAcylation 1042:1056 O-GlcNAcylation 1042:1056 O-GlcNAcylation 1042:1056 O-GlcNAcylation and nuclear translocation of NF-κB, the upstream signaling cascade of MMP activation were shown to be important for MMP activation. 27290989 7 46 theme NF-κB 1087:1091 arg1 translocation 1070:1082 nuclear translocation 1062:1082 nuclear translocation 1062:1082 O-GlcNAcylation and nuclear translocation of NF-κB, the upstream signaling cascade of MMP activation were shown to be important for MMP activation. 27290989 2 47 theme human 422:426 arg1 cancers 428:434 many human cancers 417:434 many human cancers 417:434 Aberrant O-GlcNAcylation contributes an important role in initiation and progression of many human cancers. 27290989 5 48 theme cells 809:813 arg1 migration 779:787 cell migration 774:787 cell migration 774:787 Suppression of O-GlcNAcylation using small interfering RNAs of OGT (siOGT) significantly reduced cell migration and invasion of CCA cells whereas siOGA treated cells exhibited opposite effects. 27290989 5 48 theme cells 809:813 arg1 invasion 793:800 invasion 793:800 invasion 793:800 Suppression of O-GlcNAcylation using small interfering RNAs of OGT (siOGT) significantly reduced cell migration and invasion of CCA cells whereas siOGA treated cells exhibited opposite effects. 27290989 5 49 theme O-GlcNAcylation 692:706 arg1 Suppression 677:687 Suppression 677:687 Suppression of O-GlcNAcylation using small interfering RNAs of OGT (siOGT) 677:750 Suppression of O-GlcNAcylation using small interfering RNAs of OGT (siOGT) significantly reduced cell migration and invasion of CCA cells whereas siOGA treated cells exhibited opposite effects. 27290989 9 50 theme NF-κB 1449:1453 arg1 O-GlcNAcylation 1404:1418 O-GlcNAcylation 1404:1418 O-GlcNAcylation 1404:1418 Involvement of O-GlcNAcylation in MMP-mediated migration and invasion of CCA cells was shown to be via O-GlcNAcylation and nuclear translocation of NF-κB. 27290989 9 50 theme NF-κB 1449:1453 arg1 translocation 1432:1444 nuclear translocation 1424:1444 nuclear translocation 1424:1444 Involvement of O-GlcNAcylation in MMP-mediated migration and invasion of CCA cells was shown to be via O-GlcNAcylation and nuclear translocation of NF-κB. 27290989 7 51 theme MMP 1128:1130 arg1 activation 1132:1141 MMP activation 1128:1141 MMP activation 1128:1141 O-GlcNAcylation and nuclear translocation of NF-κB, the upstream signaling cascade of MMP activation were shown to be important for MMP activation. 27290989 1 52 link O-linked 149:156 arg1 glycosylation 166:178 an O-linked protein glycosylation 146:178 an O-linked protein glycosylation with a single molecule of N-acetylglucosamine (GlcNAc) 146:233 O-GlcNAcylation, an O-linked protein glycosylation with a single molecule of N-acetylglucosamine (GlcNAc), is reversibly controlled by O-GlcNAc transferase (OGT) and N-acetyl D-glucosaminidase (OGA). 27290989 1 52 link O-linked 149:156 arg1 O-GlcNAcylation 129:143 O-GlcNAcylation 129:143 O-GlcNAcylation 129:143 O-GlcNAcylation, an O-linked protein glycosylation with a single molecule of N-acetylglucosamine (GlcNAc), is reversibly controlled by O-GlcNAc transferase (OGT) and N-acetyl D-glucosaminidase (OGA). 27290989 6 53 theme Manipulating 871:882 arg1 levels 884:889 Manipulating levels 871:889 Manipulating levels of O-GlcNAcylation 871:908 Manipulating levels of O-GlcNAcylation did affect the nuclear translocation of NF-κB and Akt-phosphorylation together with expression of matrix-metalloproteinases (MMPs). 27290989 10 54 theme metastatic 1538:1547 arg1 ability 1549:1555 the metastatic ability 1534:1555 the metastatic ability of CCA cells 1534:1568 This information indicates the significance of O-GlcNAcylation in controlling the metastatic ability of CCA cells, hence, O-GlcNAcylation and its products may be new targets for treatment of metastatic CCA. 27290989 5 55 theme small 714:718 arg1 RNAs 732:735 small interfering RNAs 714:735 small interfering RNAs of OGT (siOGT) 714:750 Suppression of O-GlcNAcylation using small interfering RNAs of OGT (siOGT) significantly reduced cell migration and invasion of CCA cells whereas siOGA treated cells exhibited opposite effects. 27290989 9 56 theme CCA 1374:1376 arg1 cells 1378:1382 CCA cells 1374:1382 CCA cells 1374:1382 Involvement of O-GlcNAcylation in MMP-mediated migration and invasion of CCA cells was shown to be via O-GlcNAcylation and nuclear translocation of NF-κB. 27290989 9 57 from Involvement 1301:1311 arg1 invasion 1362:1369 invasion 1362:1369 invasion 1362:1369 Involvement of O-GlcNAcylation in MMP-mediated migration and invasion of CCA cells was shown to be via O-GlcNAcylation and nuclear translocation of NF-κB. 27290989 9 57 from Involvement 1301:1311 arg1 migration 1348:1356 MMP-mediated migration 1335:1356 MMP-mediated migration 1335:1356 Involvement of O-GlcNAcylation in MMP-mediated migration and invasion of CCA cells was shown to be via O-GlcNAcylation and nuclear translocation of NF-κB. 27290989 5 58 theme interfering 720:730 arg1 RNAs 732:735 small interfering RNAs 714:735 small interfering RNAs of OGT (siOGT) 714:750 Suppression of O-GlcNAcylation using small interfering RNAs of OGT (siOGT) significantly reduced cell migration and invasion of CCA cells whereas siOGA treated cells exhibited opposite effects. 27290989 9 59 theme cells 1378:1382 arg1 invasion 1362:1369 invasion 1362:1369 invasion 1362:1369 Involvement of O-GlcNAcylation in MMP-mediated migration and invasion of CCA cells was shown to be via O-GlcNAcylation and nuclear translocation of NF-κB. 27290989 9 59 theme cells 1378:1382 arg1 migration 1348:1356 MMP-mediated migration 1335:1356 MMP-mediated migration 1335:1356 Involvement of O-GlcNAcylation in MMP-mediated migration and invasion of CCA cells was shown to be via O-GlcNAcylation and nuclear translocation of NF-κB. 27290989 8 60 theme increased 1265:1273 arg1 O-GlcNAcylation 1284:1298 increased cellular O-GlcNAcylation 1265:1298 increased cellular O-GlcNAcylation 1265:1298 Immunoprecipitation revealed the elevation of O-GlcNAc-modified NF-κB with increased cellular O-GlcNAcylation. 27290989 1 61 theme O-linked 149:156 arg1 glycosylation 166:178 an O-linked protein glycosylation 146:178 an O-linked protein glycosylation with a single molecule of N-acetylglucosamine (GlcNAc) 146:233 O-GlcNAcylation, an O-linked protein glycosylation with a single molecule of N-acetylglucosamine (GlcNAc), is reversibly controlled by O-GlcNAc transferase (OGT) and N-acetyl D-glucosaminidase (OGA). 27290989 1 61 theme O-linked 149:156 arg1 O-GlcNAcylation 129:143 O-GlcNAcylation 129:143 O-GlcNAcylation 129:143 O-GlcNAcylation, an O-linked protein glycosylation with a single molecule of N-acetylglucosamine (GlcNAc), is reversibly controlled by O-GlcNAc transferase (OGT) and N-acetyl D-glucosaminidase (OGA). 27290989 4 62 theme tumor 615:619 arg1 progression 621:631 tumor progression 615:631 tumor progression 615:631 In this study, the role of O-GlcNAcylation in promoting tumor progression was further investigated in CCA cell lines. 27290989 0 63 theme cells 87:91 arg1 progression 53:63 progression 53:63 progression of cholangiocarcinoma cells 53:91 Mechanistic insights of O-GlcNAcylation that promote progression of cholangiocarcinoma cells via nuclear translocation of NF-κB. 27290989 4 64 theme CCA 661:663 arg1 lines 670:674 CCA cell lines 661:674 CCA cell lines 661:674 In this study, the role of O-GlcNAcylation in promoting tumor progression was further investigated in CCA cell lines. 27290989 5 65 theme opposite 853:860 arg1 effects 862:868 opposite effects 853:868 opposite effects 853:868 Suppression of O-GlcNAcylation using small interfering RNAs of OGT (siOGT) significantly reduced cell migration and invasion of CCA cells whereas siOGA treated cells exhibited opposite effects. 27290989 1 66 theme protein 158:164 arg1 glycosylation 166:178 an O-linked protein glycosylation 146:178 an O-linked protein glycosylation with a single molecule of N-acetylglucosamine (GlcNAc) 146:233 O-GlcNAcylation, an O-linked protein glycosylation with a single molecule of N-acetylglucosamine (GlcNAc), is reversibly controlled by O-GlcNAc transferase (OGT) and N-acetyl D-glucosaminidase (OGA). 27290989 1 66 theme protein 158:164 arg1 O-GlcNAcylation 129:143 O-GlcNAcylation 129:143 O-GlcNAcylation 129:143 O-GlcNAcylation, an O-linked protein glycosylation with a single molecule of N-acetylglucosamine (GlcNAc), is reversibly controlled by O-GlcNAc transferase (OGT) and N-acetyl D-glucosaminidase (OGA). 27290989 3 67 theme cholangiocarcinoma 505:522 arg1 CCA 525:527 CCA 525:527 CCA 525:527 Elevation of O-GlcNAcylation in tumor tissues and poor prognosis of cholangiocarcinoma (CCA) patients have been reported. 27290989 3 67 theme cholangiocarcinoma 505:522 arg1 prognosis 492:500 poor prognosis 487:500 poor prognosis of cholangiocarcinoma (CCA) patients 487:537 Elevation of O-GlcNAcylation in tumor tissues and poor prognosis of cholangiocarcinoma (CCA) patients have been reported. 27290989 0 68 theme cholangiocarcinoma 68:85 arg1 cells 87:91 cholangiocarcinoma cells 68:91 cholangiocarcinoma cells 68:91 Mechanistic insights of O-GlcNAcylation that promote progression of cholangiocarcinoma cells via nuclear translocation of NF-κB. 27290989 6 69 theme Akt-phosphorylation 960:978 arg1 translocation 933:945 the nuclear translocation 921:945 the nuclear translocation of NF-κB and Akt-phosphorylation together with expression of matrix-metalloproteinases (MMPs) 921:1039 Manipulating levels of O-GlcNAcylation did affect the nuclear translocation of NF-κB and Akt-phosphorylation together with expression of matrix-metalloproteinases (MMPs). 27290989 8 70 theme cellular 1275:1282 arg1 O-GlcNAcylation 1284:1298 increased cellular O-GlcNAcylation 1265:1298 increased cellular O-GlcNAcylation 1265:1298 Immunoprecipitation revealed the elevation of O-GlcNAc-modified NF-κB with increased cellular O-GlcNAcylation. 27290989 7 71 theme MMP 1174:1176 arg1 activation 1178:1187 MMP activation 1174:1187 MMP activation 1174:1187 O-GlcNAcylation and nuclear translocation of NF-κB, the upstream signaling cascade of MMP activation were shown to be important for MMP activation. 27213235 5 0 theme diverse 896:902 arg1 pathways 904:911 diverse pathways 896:911 diverse pathways 896:911 In total, 86 mitochondrial proteins, involved in diverse pathways, were O-GlcNAcylated. 27213235 4 1 theme DTT 778:780 arg1 BEMAD 792:796 BEMAD 792:796 BEMAD 792:796 We performed a comparative O-GlcNAc profiling of mitochondria from control and streptozotocin (STZ)-induced diabetic rat hearts by using an improved β-elimination/Michael addition with isotopic DTT reagents (BEMAD) followed by tandem mass spectrometric analysis. 27213235 4 1 theme DTT 778:780 arg1 reagents 782:789 isotopic DTT reagents 769:789 isotopic DTT reagents (BEMAD) followed by tandem mass spectrometric analysis 769:844 We performed a comparative O-GlcNAc profiling of mitochondria from control and streptozotocin (STZ)-induced diabetic rat hearts by using an improved β-elimination/Michael addition with isotopic DTT reagents (BEMAD) followed by tandem mass spectrometric analysis. 27213235 5 2 from total 850:854 arg1 O-GlcNAcylated 919:932 O-GlcNAcylated 919:932 O-GlcNAcylated 919:932 In total, 86 mitochondrial proteins, involved in diverse pathways, were O-GlcNAcylated. 27213235 4 3 theme isotopic 769:776 arg1 BEMAD 792:796 BEMAD 792:796 BEMAD 792:796 We performed a comparative O-GlcNAc profiling of mitochondria from control and streptozotocin (STZ)-induced diabetic rat hearts by using an improved β-elimination/Michael addition with isotopic DTT reagents (BEMAD) followed by tandem mass spectrometric analysis. 27213235 4 3 theme isotopic 769:776 arg1 reagents 782:789 isotopic DTT reagents 769:789 isotopic DTT reagents (BEMAD) followed by tandem mass spectrometric analysis 769:844 We performed a comparative O-GlcNAc profiling of mitochondria from control and streptozotocin (STZ)-induced diabetic rat hearts by using an improved β-elimination/Michael addition with isotopic DTT reagents (BEMAD) followed by tandem mass spectrometric analysis. 27213235 1 4 link O-linked 94:101 arg1 modification 158:169 a post-translational modification 137:169 a post-translational modification on serine and threonine residues of many proteins 137:219 O-linked β-N-acetylglucosamine (O-GlcNAc), a post-translational modification on serine and threonine residues of many proteins, plays crucial regulatory roles in diverse biological events. 27213235 1 4 link O-linked 94:101 arg1 O-GlcNAc 126:133 O-GlcNAc 126:133 O-GlcNAc 126:133 O-linked β-N-acetylglucosamine (O-GlcNAc), a post-translational modification on serine and threonine residues of many proteins, plays crucial regulatory roles in diverse biological events. 27213235 1 4 link O-linked 94:101 arg1 β-N-acetylglucosamine 103:123 O-linked β-N-acetylglucosamine 94:123 O-linked β-N-acetylglucosamine (O-GlcNAc) 94:134 O-linked β-N-acetylglucosamine (O-GlcNAc), a post-translational modification on serine and threonine residues of many proteins, plays crucial regulatory roles in diverse biological events. 27213235 6 5 theme site-specific 966:978 arg1 alterations 980:990 site-specific alterations 966:990 site-specific alterations in O-GlcNAcylation 966:1009 Among them, many proteins have site-specific alterations in O-GlcNAcylation in response to diabetes, which suggests that protein O-GlcNAcylation is a novel layer of regulation mediating adaptive changes in mitochondrial metabolism during the progression of diabetic cardiomyopathy. 27213235 4 6 theme spectrometric 823:835 arg1 analysis 837:844 tandem mass spectrometric analysis 811:844 tandem mass spectrometric analysis 811:844 We performed a comparative O-GlcNAc profiling of mitochondria from control and streptozotocin (STZ)-induced diabetic rat hearts by using an improved β-elimination/Michael addition with isotopic DTT reagents (BEMAD) followed by tandem mass spectrometric analysis. 27213235 2 7 theme O-GlcNAc 305:312 arg1 O-GlcNAcylation 328:342 O-GlcNAcylation 328:342 O-GlcNAcylation 328:342 As a nutrient sensor, O-GlcNAc modification (O-GlcNAcylation) on nuclear and cytoplasmic proteins underlies the pathology of diabetic complications including cardiomyopathy. 27213235 2 7 theme O-GlcNAc 305:312 arg1 modification 314:325 O-GlcNAc modification 305:325 O-GlcNAc modification (O-GlcNAcylation) on nuclear and cytoplasmic proteins 305:379 As a nutrient sensor, O-GlcNAc modification (O-GlcNAcylation) on nuclear and cytoplasmic proteins underlies the pathology of diabetic complications including cardiomyopathy. 27213235 6 8 theme protein 1056:1062 arg1 layer 1091:1095 a novel layer 1083:1095 a novel layer of regulation mediating adaptive changes in mitochondrial metabolism during the progression of diabetic cardiomyopathy 1083:1214 Among them, many proteins have site-specific alterations in O-GlcNAcylation in response to diabetes, which suggests that protein O-GlcNAcylation is a novel layer of regulation mediating adaptive changes in mitochondrial metabolism during the progression of diabetic cardiomyopathy. 27213235 6 8 theme protein 1056:1062 arg1 O-GlcNAcylation 1064:1078 protein O-GlcNAcylation 1056:1078 protein O-GlcNAcylation 1056:1078 Among them, many proteins have site-specific alterations in O-GlcNAcylation in response to diabetes, which suggests that protein O-GlcNAcylation is a novel layer of regulation mediating adaptive changes in mitochondrial metabolism during the progression of diabetic cardiomyopathy. 27213235 4 9 from control 651:657 arg1 profiling 620:628 a comparative O-GlcNAc profiling 597:628 a comparative O-GlcNAc profiling of mitochondria from control and streptozotocin (STZ)-induced diabetic rat hearts 597:710 We performed a comparative O-GlcNAc profiling of mitochondria from control and streptozotocin (STZ)-induced diabetic rat hearts by using an improved β-elimination/Michael addition with isotopic DTT reagents (BEMAD) followed by tandem mass spectrometric analysis. 27213235 4 9 from control 651:657 arg1 mitochondria 633:644 mitochondria 633:644 mitochondria from control and streptozotocin (STZ)-induced diabetic rat hearts 633:710 We performed a comparative O-GlcNAc profiling of mitochondria from control and streptozotocin (STZ)-induced diabetic rat hearts by using an improved β-elimination/Michael addition with isotopic DTT reagents (BEMAD) followed by tandem mass spectrometric analysis. 27213235 4 10 theme diabetic 692:699 arg1 hearts 705:710 diabetic rat hearts 692:710 diabetic rat hearts 692:710 We performed a comparative O-GlcNAc profiling of mitochondria from control and streptozotocin (STZ)-induced diabetic rat hearts by using an improved β-elimination/Michael addition with isotopic DTT reagents (BEMAD) followed by tandem mass spectrometric analysis. 27213235 1 11 theme O-linked 94:101 arg1 modification 158:169 a post-translational modification 137:169 a post-translational modification on serine and threonine residues of many proteins 137:219 O-linked β-N-acetylglucosamine (O-GlcNAc), a post-translational modification on serine and threonine residues of many proteins, plays crucial regulatory roles in diverse biological events. 27213235 1 11 theme O-linked 94:101 arg1 O-GlcNAc 126:133 O-GlcNAc 126:133 O-GlcNAc 126:133 O-linked β-N-acetylglucosamine (O-GlcNAc), a post-translational modification on serine and threonine residues of many proteins, plays crucial regulatory roles in diverse biological events. 27213235 1 11 theme O-linked 94:101 arg1 β-N-acetylglucosamine 103:123 O-linked β-N-acetylglucosamine 94:123 O-linked β-N-acetylglucosamine (O-GlcNAc) 94:134 O-linked β-N-acetylglucosamine (O-GlcNAc), a post-translational modification on serine and threonine residues of many proteins, plays crucial regulatory roles in diverse biological events. 27213235 2 12 theme complications 417:429 arg1 sensor 297:302 a nutrient sensor 286:302 a nutrient sensor 286:302 As a nutrient sensor, O-GlcNAc modification (O-GlcNAcylation) on nuclear and cytoplasmic proteins underlies the pathology of diabetic complications including cardiomyopathy. 27213235 2 12 theme complications 417:429 arg1 pathology 395:403 the pathology 391:403 the pathology of diabetic complications including cardiomyopathy 391:454 As a nutrient sensor, O-GlcNAc modification (O-GlcNAcylation) on nuclear and cytoplasmic proteins underlies the pathology of diabetic complications including cardiomyopathy. 27213235 0 13 from O-GlcNAcylation 58:72 arg1 Hearts 86:91 Diabetic Hearts 77:91 Diabetic Hearts 77:91 Comparative Proteomics Reveals Dysregulated Mitochondrial O-GlcNAcylation in Diabetic Hearts. 27213235 1 14 from modification 158:169 arg1 threonine 185:193 threonine 185:193 threonine 185:193 O-linked β-N-acetylglucosamine (O-GlcNAc), a post-translational modification on serine and threonine residues of many proteins, plays crucial regulatory roles in diverse biological events. 27213235 1 14 from modification 158:169 arg1 serine 174:179 serine 174:179 serine 174:179 O-linked β-N-acetylglucosamine (O-GlcNAc), a post-translational modification on serine and threonine residues of many proteins, plays crucial regulatory roles in diverse biological events. 27213235 1 15 theme many 207:210 arg1 proteins 212:219 many proteins 207:219 many proteins 207:219 O-linked β-N-acetylglucosamine (O-GlcNAc), a post-translational modification on serine and threonine residues of many proteins, plays crucial regulatory roles in diverse biological events. 27213235 6 16 from alterations 980:990 arg1 O-GlcNAcylation 995:1009 O-GlcNAcylation 995:1009 O-GlcNAcylation 995:1009 Among them, many proteins have site-specific alterations in O-GlcNAcylation in response to diabetes, which suggests that protein O-GlcNAcylation is a novel layer of regulation mediating adaptive changes in mitochondrial metabolism during the progression of diabetic cardiomyopathy. 27213235 1 17 theme proteins 212:219 arg1 threonine 185:193 threonine 185:193 threonine 185:193 O-linked β-N-acetylglucosamine (O-GlcNAc), a post-translational modification on serine and threonine residues of many proteins, plays crucial regulatory roles in diverse biological events. 27213235 1 17 theme proteins 212:219 arg1 serine 174:179 serine 174:179 serine 174:179 O-linked β-N-acetylglucosamine (O-GlcNAc), a post-translational modification on serine and threonine residues of many proteins, plays crucial regulatory roles in diverse biological events. 27213235 0 18 theme Comparative 0:10 arg1 Proteomics 12:21 Comparative Proteomics 0:21 Comparative Proteomics 0:21 Comparative Proteomics Reveals Dysregulated Mitochondrial O-GlcNAcylation in Diabetic Hearts. 27213235 2 19 theme diabetic 408:415 arg1 cardiomyopathy 441:454 cardiomyopathy 441:454 cardiomyopathy 441:454 As a nutrient sensor, O-GlcNAc modification (O-GlcNAcylation) on nuclear and cytoplasmic proteins underlies the pathology of diabetic complications including cardiomyopathy. 27213235 2 19 theme diabetic 408:415 arg1 complications 417:429 diabetic complications 408:429 diabetic complications including cardiomyopathy 408:454 As a nutrient sensor, O-GlcNAc modification (O-GlcNAcylation) on nuclear and cytoplasmic proteins underlies the pathology of diabetic complications including cardiomyopathy. 27213235 0 20 theme Dysregulated 31:42 arg1 O-GlcNAcylation 58:72 Dysregulated Mitochondrial O-GlcNAcylation 31:72 Dysregulated Mitochondrial O-GlcNAcylation in Diabetic Hearts 31:91 Comparative Proteomics Reveals Dysregulated Mitochondrial O-GlcNAcylation in Diabetic Hearts. 27213235 4 21 theme O-GlcNAc 611:618 arg1 profiling 620:628 a comparative O-GlcNAc profiling 597:628 a comparative O-GlcNAc profiling of mitochondria from control and streptozotocin (STZ)-induced diabetic rat hearts 597:710 We performed a comparative O-GlcNAc profiling of mitochondria from control and streptozotocin (STZ)-induced diabetic rat hearts by using an improved β-elimination/Michael addition with isotopic DTT reagents (BEMAD) followed by tandem mass spectrometric analysis. 27213235 6 22 from changes 1130:1136 arg1 metabolism 1155:1164 mitochondrial metabolism 1141:1164 mitochondrial metabolism 1141:1164 Among them, many proteins have site-specific alterations in O-GlcNAcylation in response to diabetes, which suggests that protein O-GlcNAcylation is a novel layer of regulation mediating adaptive changes in mitochondrial metabolism during the progression of diabetic cardiomyopathy. 27213235 1 23 dep serine 174:179 arg1 residues 195:202 residues 195:202 residues 195:202 O-linked β-N-acetylglucosamine (O-GlcNAc), a post-translational modification on serine and threonine residues of many proteins, plays crucial regulatory roles in diverse biological events. 27213235 3 24 theme chronic 523:529 arg1 hyperglycemia 531:543 chronic hyperglycemia 523:543 chronic hyperglycemia in diabetes 523:555 However, mitochondrial O-GlcNAcylation, especially in response to chronic hyperglycemia in diabetes, has been poorly explored. 27213235 4 25 theme mitochondria 633:644 arg1 profiling 620:628 a comparative O-GlcNAc profiling 597:628 a comparative O-GlcNAc profiling of mitochondria from control and streptozotocin (STZ)-induced diabetic rat hearts 597:710 We performed a comparative O-GlcNAc profiling of mitochondria from control and streptozotocin (STZ)-induced diabetic rat hearts by using an improved β-elimination/Michael addition with isotopic DTT reagents (BEMAD) followed by tandem mass spectrometric analysis. 27213235 4 26 theme tandem 811:816 arg1 analysis 837:844 tandem mass spectrometric analysis 811:844 tandem mass spectrometric analysis 811:844 We performed a comparative O-GlcNAc profiling of mitochondria from control and streptozotocin (STZ)-induced diabetic rat hearts by using an improved β-elimination/Michael addition with isotopic DTT reagents (BEMAD) followed by tandem mass spectrometric analysis. 27213235 1 27 theme crucial 228:234 arg1 roles 247:251 crucial regulatory roles 228:251 crucial regulatory roles 228:251 O-linked β-N-acetylglucosamine (O-GlcNAc), a post-translational modification on serine and threonine residues of many proteins, plays crucial regulatory roles in diverse biological events. 27213235 2 28 theme cytoplasmic 360:370 arg1 proteins 372:379 nuclear and cytoplasmic proteins 348:379 nuclear and cytoplasmic proteins 348:379 As a nutrient sensor, O-GlcNAc modification (O-GlcNAcylation) on nuclear and cytoplasmic proteins underlies the pathology of diabetic complications including cardiomyopathy. 27213235 6 29 theme adaptive 1121:1128 arg1 changes 1130:1136 adaptive changes 1121:1136 adaptive changes in mitochondrial metabolism 1121:1164 Among them, many proteins have site-specific alterations in O-GlcNAcylation in response to diabetes, which suggests that protein O-GlcNAcylation is a novel layer of regulation mediating adaptive changes in mitochondrial metabolism during the progression of diabetic cardiomyopathy. 27213235 4 30 theme improved 724:731 arg1 addition 755:762 an improved β-elimination/Michael addition 721:762 an improved β-elimination/Michael addition 721:762 We performed a comparative O-GlcNAc profiling of mitochondria from control and streptozotocin (STZ)-induced diabetic rat hearts by using an improved β-elimination/Michael addition with isotopic DTT reagents (BEMAD) followed by tandem mass spectrometric analysis. 27213235 1 31 theme regulatory 236:245 arg1 roles 247:251 crucial regulatory roles 228:251 crucial regulatory roles 228:251 O-linked β-N-acetylglucosamine (O-GlcNAc), a post-translational modification on serine and threonine residues of many proteins, plays crucial regulatory roles in diverse biological events. 27213235 0 32 theme Mitochondrial 44:56 arg1 O-GlcNAcylation 58:72 Dysregulated Mitochondrial O-GlcNAcylation 31:72 Dysregulated Mitochondrial O-GlcNAcylation in Diabetic Hearts 31:91 Comparative Proteomics Reveals Dysregulated Mitochondrial O-GlcNAcylation in Diabetic Hearts. 27213235 3 33 theme mitochondrial 466:478 arg1 O-GlcNAcylation 480:494 mitochondrial O-GlcNAcylation 466:494 mitochondrial O-GlcNAcylation 466:494 However, mitochondrial O-GlcNAcylation, especially in response to chronic hyperglycemia in diabetes, has been poorly explored. 27213235 4 34 dep control 651:657 arg1 hearts 705:710 diabetic rat hearts 692:710 diabetic rat hearts 692:710 We performed a comparative O-GlcNAc profiling of mitochondria from control and streptozotocin (STZ)-induced diabetic rat hearts by using an improved β-elimination/Michael addition with isotopic DTT reagents (BEMAD) followed by tandem mass spectrometric analysis. 27213235 4 35 from profiling 620:628 arg1 control 651:657 control 651:657 control 651:657 We performed a comparative O-GlcNAc profiling of mitochondria from control and streptozotocin (STZ)-induced diabetic rat hearts by using an improved β-elimination/Michael addition with isotopic DTT reagents (BEMAD) followed by tandem mass spectrometric analysis. 27213235 4 35 from profiling 620:628 arg1 -induced 683:690 -induced 683:690 -induced 683:690 We performed a comparative O-GlcNAc profiling of mitochondria from control and streptozotocin (STZ)-induced diabetic rat hearts by using an improved β-elimination/Michael addition with isotopic DTT reagents (BEMAD) followed by tandem mass spectrometric analysis. 27213235 6 36 contain have 961:964 arg1 proteins 952:959 many proteins 947:959 many proteins 947:959 Among them, many proteins have site-specific alterations in O-GlcNAcylation in response to diabetes, which suggests that protein O-GlcNAcylation is a novel layer of regulation mediating adaptive changes in mitochondrial metabolism during the progression of diabetic cardiomyopathy. 27213235 6 36 contain have 961:964 arg2 alterations 980:990 site-specific alterations 966:990 site-specific alterations in O-GlcNAcylation 966:1009 Among them, many proteins have site-specific alterations in O-GlcNAcylation in response to diabetes, which suggests that protein O-GlcNAcylation is a novel layer of regulation mediating adaptive changes in mitochondrial metabolism during the progression of diabetic cardiomyopathy. 27213235 0 37 theme Diabetic 77:84 arg1 Hearts 86:91 Diabetic Hearts 77:91 Diabetic Hearts 77:91 Comparative Proteomics Reveals Dysregulated Mitochondrial O-GlcNAcylation in Diabetic Hearts. 27213235 4 38 theme β-elimination/Michael 733:753 arg1 addition 755:762 an improved β-elimination/Michael addition 721:762 an improved β-elimination/Michael addition 721:762 We performed a comparative O-GlcNAc profiling of mitochondria from control and streptozotocin (STZ)-induced diabetic rat hearts by using an improved β-elimination/Michael addition with isotopic DTT reagents (BEMAD) followed by tandem mass spectrometric analysis. 27213235 6 39 theme many 947:950 arg1 proteins 952:959 many proteins 947:959 many proteins 947:959 Among them, many proteins have site-specific alterations in O-GlcNAcylation in response to diabetes, which suggests that protein O-GlcNAcylation is a novel layer of regulation mediating adaptive changes in mitochondrial metabolism during the progression of diabetic cardiomyopathy. 27213235 5 40 theme mitochondrial 860:872 arg1 proteins 874:881 86 mitochondrial proteins 857:881 86 mitochondrial proteins 857:881 In total, 86 mitochondrial proteins, involved in diverse pathways, were O-GlcNAcylated. 27213235 4 41 theme comparative 599:609 arg1 profiling 620:628 a comparative O-GlcNAc profiling 597:628 a comparative O-GlcNAc profiling of mitochondria from control and streptozotocin (STZ)-induced diabetic rat hearts 597:710 We performed a comparative O-GlcNAc profiling of mitochondria from control and streptozotocin (STZ)-induced diabetic rat hearts by using an improved β-elimination/Michael addition with isotopic DTT reagents (BEMAD) followed by tandem mass spectrometric analysis. 27213235 1 42 theme post-translational 139:156 arg1 modification 158:169 a post-translational modification 137:169 a post-translational modification on serine and threonine residues of many proteins 137:219 O-linked β-N-acetylglucosamine (O-GlcNAc), a post-translational modification on serine and threonine residues of many proteins, plays crucial regulatory roles in diverse biological events. 27213235 1 42 theme post-translational 139:156 arg1 β-N-acetylglucosamine 103:123 O-linked β-N-acetylglucosamine 94:123 O-linked β-N-acetylglucosamine (O-GlcNAc) 94:134 O-linked β-N-acetylglucosamine (O-GlcNAc), a post-translational modification on serine and threonine residues of many proteins, plays crucial regulatory roles in diverse biological events. 27213235 6 43 dep diabetes 1026:1033 arg1 response 1014:1021 response 1014:1021 response 1014:1021 Among them, many proteins have site-specific alterations in O-GlcNAcylation in response to diabetes, which suggests that protein O-GlcNAcylation is a novel layer of regulation mediating adaptive changes in mitochondrial metabolism during the progression of diabetic cardiomyopathy. 27213235 6 44 dep have 961:964 arg1 suggests 1042:1049 suggests 1042:1049 suggests that protein O-GlcNAcylation is a novel layer of regulation mediating adaptive changes in mitochondrial metabolism during the progression of diabetic cardiomyopathy 1042:1214 Among them, many proteins have site-specific alterations in O-GlcNAcylation in response to diabetes, which suggests that protein O-GlcNAcylation is a novel layer of regulation mediating adaptive changes in mitochondrial metabolism during the progression of diabetic cardiomyopathy. 27213235 2 45 theme nutrient 288:295 arg1 sensor 297:302 a nutrient sensor 286:302 a nutrient sensor 286:302 As a nutrient sensor, O-GlcNAc modification (O-GlcNAcylation) on nuclear and cytoplasmic proteins underlies the pathology of diabetic complications including cardiomyopathy. 27213235 2 45 theme nutrient 288:295 arg1 pathology 395:403 the pathology 391:403 the pathology of diabetic complications including cardiomyopathy 391:454 As a nutrient sensor, O-GlcNAc modification (O-GlcNAcylation) on nuclear and cytoplasmic proteins underlies the pathology of diabetic complications including cardiomyopathy. 27213235 3 46 from hyperglycemia 531:543 arg1 diabetes 548:555 diabetes 548:555 diabetes 548:555 However, mitochondrial O-GlcNAcylation, especially in response to chronic hyperglycemia in diabetes, has been poorly explored. 27213235 4 47 theme mass 818:821 arg1 analysis 837:844 tandem mass spectrometric analysis 811:844 tandem mass spectrometric analysis 811:844 We performed a comparative O-GlcNAc profiling of mitochondria from control and streptozotocin (STZ)-induced diabetic rat hearts by using an improved β-elimination/Michael addition with isotopic DTT reagents (BEMAD) followed by tandem mass spectrometric analysis. 27213235 6 48 theme regulation 1100:1109 arg1 layer 1091:1095 a novel layer 1083:1095 a novel layer of regulation mediating adaptive changes in mitochondrial metabolism during the progression of diabetic cardiomyopathy 1083:1214 Among them, many proteins have site-specific alterations in O-GlcNAcylation in response to diabetes, which suggests that protein O-GlcNAcylation is a novel layer of regulation mediating adaptive changes in mitochondrial metabolism during the progression of diabetic cardiomyopathy. 27213235 6 48 theme regulation 1100:1109 arg1 O-GlcNAcylation 1064:1078 protein O-GlcNAcylation 1056:1078 protein O-GlcNAcylation 1056:1078 Among them, many proteins have site-specific alterations in O-GlcNAcylation in response to diabetes, which suggests that protein O-GlcNAcylation is a novel layer of regulation mediating adaptive changes in mitochondrial metabolism during the progression of diabetic cardiomyopathy. 27213235 6 49 theme mitochondrial 1141:1153 arg1 metabolism 1155:1164 mitochondrial metabolism 1141:1164 mitochondrial metabolism 1141:1164 Among them, many proteins have site-specific alterations in O-GlcNAcylation in response to diabetes, which suggests that protein O-GlcNAcylation is a novel layer of regulation mediating adaptive changes in mitochondrial metabolism during the progression of diabetic cardiomyopathy. 27213235 2 50 theme nuclear 348:354 arg1 proteins 372:379 nuclear and cytoplasmic proteins 348:379 nuclear and cytoplasmic proteins 348:379 As a nutrient sensor, O-GlcNAc modification (O-GlcNAcylation) on nuclear and cytoplasmic proteins underlies the pathology of diabetic complications including cardiomyopathy. 27213235 2 51 from modification 314:325 arg1 proteins 372:379 nuclear and cytoplasmic proteins 348:379 nuclear and cytoplasmic proteins 348:379 As a nutrient sensor, O-GlcNAc modification (O-GlcNAcylation) on nuclear and cytoplasmic proteins underlies the pathology of diabetic complications including cardiomyopathy. 27213235 1 52 theme diverse 256:262 arg1 events 275:280 diverse biological events 256:280 diverse biological events 256:280 O-linked β-N-acetylglucosamine (O-GlcNAc), a post-translational modification on serine and threonine residues of many proteins, plays crucial regulatory roles in diverse biological events. 27213235 4 53 from -induced 683:690 arg1 profiling 620:628 a comparative O-GlcNAc profiling 597:628 a comparative O-GlcNAc profiling of mitochondria from control and streptozotocin (STZ)-induced diabetic rat hearts 597:710 We performed a comparative O-GlcNAc profiling of mitochondria from control and streptozotocin (STZ)-induced diabetic rat hearts by using an improved β-elimination/Michael addition with isotopic DTT reagents (BEMAD) followed by tandem mass spectrometric analysis. 27213235 4 53 from -induced 683:690 arg1 mitochondria 633:644 mitochondria 633:644 mitochondria from control and streptozotocin (STZ)-induced diabetic rat hearts 633:710 We performed a comparative O-GlcNAc profiling of mitochondria from control and streptozotocin (STZ)-induced diabetic rat hearts by using an improved β-elimination/Michael addition with isotopic DTT reagents (BEMAD) followed by tandem mass spectrometric analysis. 27213235 4 54 theme rat 701:703 arg1 hearts 705:710 diabetic rat hearts 692:710 diabetic rat hearts 692:710 We performed a comparative O-GlcNAc profiling of mitochondria from control and streptozotocin (STZ)-induced diabetic rat hearts by using an improved β-elimination/Michael addition with isotopic DTT reagents (BEMAD) followed by tandem mass spectrometric analysis. 27213235 6 55 theme cardiomyopathy 1201:1214 arg1 progression 1177:1187 the progression 1173:1187 the progression of diabetic cardiomyopathy 1173:1214 Among them, many proteins have site-specific alterations in O-GlcNAcylation in response to diabetes, which suggests that protein O-GlcNAcylation is a novel layer of regulation mediating adaptive changes in mitochondrial metabolism during the progression of diabetic cardiomyopathy. 27213235 1 56 theme biological 264:273 arg1 events 275:280 diverse biological events 256:280 diverse biological events 256:280 O-linked β-N-acetylglucosamine (O-GlcNAc), a post-translational modification on serine and threonine residues of many proteins, plays crucial regulatory roles in diverse biological events. 27213235 3 57 dep hyperglycemia 531:543 arg1 response 511:518 response 511:518 response 511:518 However, mitochondrial O-GlcNAcylation, especially in response to chronic hyperglycemia in diabetes, has been poorly explored. 27213235 5 58 from O-GlcNAcylated 919:932 arg1 total 850:854 total 850:854 total 850:854 In total, 86 mitochondrial proteins, involved in diverse pathways, were O-GlcNAcylated. 27213235 6 59 theme diabetic 1192:1199 arg1 cardiomyopathy 1201:1214 diabetic cardiomyopathy 1192:1214 diabetic cardiomyopathy 1192:1214 Among them, many proteins have site-specific alterations in O-GlcNAcylation in response to diabetes, which suggests that protein O-GlcNAcylation is a novel layer of regulation mediating adaptive changes in mitochondrial metabolism during the progression of diabetic cardiomyopathy. 27213235 6 60 theme novel 1085:1089 arg1 layer 1091:1095 a novel layer 1083:1095 a novel layer of regulation mediating adaptive changes in mitochondrial metabolism during the progression of diabetic cardiomyopathy 1083:1214 Among them, many proteins have site-specific alterations in O-GlcNAcylation in response to diabetes, which suggests that protein O-GlcNAcylation is a novel layer of regulation mediating adaptive changes in mitochondrial metabolism during the progression of diabetic cardiomyopathy. 27213235 6 60 theme novel 1085:1089 arg1 O-GlcNAcylation 1064:1078 protein O-GlcNAcylation 1056:1078 protein O-GlcNAcylation 1056:1078 Among them, many proteins have site-specific alterations in O-GlcNAcylation in response to diabetes, which suggests that protein O-GlcNAcylation is a novel layer of regulation mediating adaptive changes in mitochondrial metabolism during the progression of diabetic cardiomyopathy. 26632978 10 0 from advances 1759:1766 arg1 analysis 1785:1792 transcriptome analysis 1771:1792 transcriptome analysis using next generation sequencing platforms 1771:1835 Technological advances in transcriptome analysis using next generation sequencing platforms and proteome analysis by highly sensitive tandem mass spectrometry allowed a more comprehensive interrogation of three underinvestigated brown snake (Pseudonaja) venoms uncovering many novel peptide sequences that are unique to these closely related species. 26632978 10 0 from advances 1759:1766 arg1 analysis 1850:1857 proteome analysis 1841:1857 proteome analysis by highly sensitive tandem mass spectrometry 1841:1902 Technological advances in transcriptome analysis using next generation sequencing platforms and proteome analysis by highly sensitive tandem mass spectrometry allowed a more comprehensive interrogation of three underinvestigated brown snake (Pseudonaja) venoms uncovering many novel peptide sequences that are unique to these closely related species. 26632978 5 1 theme venom 691:695 arg1 proteome 697:704 each venom proteome 686:704 each venom proteome 686:704 Integration of each venom proteome with the corresponding annotated reads identified 65 isoforms from six toxin families; high sequence coverage highlighted subtle differences between sequences and intra and inter-specific variation between species. 26632978 6 2 theme natriuretic 980:990 arg1 peptides 992:999 natriuretic peptides 980:999 natriuretic peptides from P. aspidorhyncha and P. nuchaliscontaining O-linked trisaccharides with high homology to the glycosylated region of TNPc 980:1125 High quality MS/MS data identified unusual glycoforms with natriuretic peptides from P. aspidorhyncha and P. nuchaliscontaining O-linked trisaccharides with high homology to the glycosylated region of TNPc. 26632978 11 3 theme other 2170:2174 arg1 snakes 2185:2190 other venomous snakes 2170:2190 other venomous snakes for a deeper understanding of venom composition, envenomation, venom evolution, 2170:2270 This generic strategy will provide invaluable information when applied to other venomous snakes for a deeper understanding of venom composition, envenomation, venom evolution, as well as identifying research tools and drug leads. 26632978 6 4 with trisaccharides 1058:1071 arg1 homology 1083:1090 high homology 1078:1090 high homology to the glycosylated region of TNPc 1078:1125 High quality MS/MS data identified unusual glycoforms with natriuretic peptides from P. aspidorhyncha and P. nuchaliscontaining O-linked trisaccharides with high homology to the glycosylated region of TNPc. 26632978 9 5 theme venomics 1723:1730 arg1 methodology 1732:1742 deep venomics methodology 1718:1742 deep venomics methodology 1718:1742 BIOLOGICAL SIGNIFICANCE Mining Australia's vastly untapped source of toxins from its venomous creatures has been significantly advanced by employing deep venomics methodology. 26632978 10 6 theme brown 1974:1978 arg1 venoms 1999:2004 three underinvestigated brown snake (Pseudonaja) venoms 1950:2004 three underinvestigated brown snake (Pseudonaja) venoms uncovering many novel peptide sequences that are unique to these closely related species 1950:2093 Technological advances in transcriptome analysis using next generation sequencing platforms and proteome analysis by highly sensitive tandem mass spectrometry allowed a more comprehensive interrogation of three underinvestigated brown snake (Pseudonaja) venoms uncovering many novel peptide sequences that are unique to these closely related species. 26632978 9 7 theme BIOLOGICAL 1569:1578 arg1 SIGNIFICANCE 1580:1591 BIOLOGICAL SIGNIFICANCE 1569:1591 BIOLOGICAL SIGNIFICANCE Mining Australia's vastly untapped source of toxins from its venomous creatures 1569:1671 BIOLOGICAL SIGNIFICANCE Mining Australia's vastly untapped source of toxins from its venomous creatures has been significantly advanced by employing deep venomics methodology. 26632978 11 8 dep drug 2314:2317 arg1 leads 2319:2323 leads 2319:2323 leads 2319:2323 This generic strategy will provide invaluable information when applied to other venomous snakes for a deeper understanding of venom composition, envenomation, venom evolution, as well as identifying research tools and drug leads. 26632978 0 9 theme Deep 0:3 arg1 venomics 5:12 Deep venomics 0:12 Deep venomics of the Pseudonaja genus 0:36 Deep venomics of the Pseudonaja genus reveals inter- and intra-specific variation. 26632978 10 10 theme transcriptome 1771:1783 arg1 analysis 1785:1792 transcriptome analysis 1771:1792 transcriptome analysis using next generation sequencing platforms 1771:1835 Technological advances in transcriptome analysis using next generation sequencing platforms and proteome analysis by highly sensitive tandem mass spectrometry allowed a more comprehensive interrogation of three underinvestigated brown snake (Pseudonaja) venoms uncovering many novel peptide sequences that are unique to these closely related species. 26632978 7 11 theme toxin 1206:1210 arg1 families 1212:1219 all toxin families 1202:1219 all toxin families with the exception of both natriuretic peptides and P. aspidorhyncha PLA2s that were found to be evolutionarily constrained under purifying selection pressures 1202:1379 Molecular evolutionary assessments indicated the accelerated evolution of all toxin families with the exception of both natriuretic peptides and P. aspidorhyncha PLA2s that were found to be evolutionarily constrained under purifying selection pressures. 26632978 5 12 from families 783:790 arg1 isoforms 759:766 65 isoforms 756:766 65 isoforms from six toxin families; high sequence coverage highlighted subtle differences between sequences and intra and inter-specific variation between species 756:918 Integration of each venom proteome with the corresponding annotated reads identified 65 isoforms from six toxin families; high sequence coverage highlighted subtle differences between sequences and intra and inter-specific variation between species. 26632978 11 13 theme venom 2255:2259 arg1 evolution 2261:2269 venom evolution 2255:2269 venom evolution 2255:2269 This generic strategy will provide invaluable information when applied to other venomous snakes for a deeper understanding of venom composition, envenomation, venom evolution, as well as identifying research tools and drug leads. 26632978 11 13 theme venom 2255:2259 arg1 composition 2228:2238 venom composition 2222:2238 venom composition 2222:2238 This generic strategy will provide invaluable information when applied to other venomous snakes for a deeper understanding of venom composition, envenomation, venom evolution, as well as identifying research tools and drug leads. 26632978 9 14 theme untapped 1619:1626 arg1 source 1628:1633 Australia's vastly untapped source 1600:1633 Australia's vastly untapped source of toxins from its venomous creatures 1600:1671 BIOLOGICAL SIGNIFICANCE Mining Australia's vastly untapped source of toxins from its venomous creatures has been significantly advanced by employing deep venomics methodology. 26632978 6 15 theme O-linked 1049:1056 arg1 trisaccharides 1058:1071 O-linked trisaccharides 1049:1071 O-linked trisaccharides with high homology to the glycosylated region of TNPc 1049:1125 High quality MS/MS data identified unusual glycoforms with natriuretic peptides from P. aspidorhyncha and P. nuchaliscontaining O-linked trisaccharides with high homology to the glycosylated region of TNPc. 26632978 6 16 dep aspidorhyncha 1009:1021 arg1 trisaccharides 1058:1071 O-linked trisaccharides 1049:1071 O-linked trisaccharides with high homology to the glycosylated region of TNPc 1049:1125 High quality MS/MS data identified unusual glycoforms with natriuretic peptides from P. aspidorhyncha and P. nuchaliscontaining O-linked trisaccharides with high homology to the glycosylated region of TNPc. 26632978 8 17 theme wide 1408:1411 arg1 range 1413:1417 a wide range 1406:1417 a wide range of novel peptide sequences from six bioactive peptide families 1406:1480 This study has revealed a wide range of novel peptide sequences from six bioactive peptide families and highlights the subtle differences between toxins in these closely related species. 26632978 10 18 theme generation 1805:1814 arg1 platforms 1827:1835 next generation sequencing platforms 1800:1835 next generation sequencing platforms 1800:1835 Technological advances in transcriptome analysis using next generation sequencing platforms and proteome analysis by highly sensitive tandem mass spectrometry allowed a more comprehensive interrogation of three underinvestigated brown snake (Pseudonaja) venoms uncovering many novel peptide sequences that are unique to these closely related species. 26632978 7 19 theme accelerated 1177:1187 arg1 evolution 1189:1197 the accelerated evolution 1173:1197 the accelerated evolution of all toxin families with the exception of both natriuretic peptides and P. aspidorhyncha PLA2s that were found to be evolutionarily constrained under purifying selection pressures 1173:1379 Molecular evolutionary assessments indicated the accelerated evolution of all toxin families with the exception of both natriuretic peptides and P. aspidorhyncha PLA2s that were found to be evolutionarily constrained under purifying selection pressures. 26632978 6 20 link O-linked 1049:1056 arg1 trisaccharides 1058:1071 O-linked trisaccharides 1049:1071 O-linked trisaccharides with high homology to the glycosylated region of TNPc 1049:1125 High quality MS/MS data identified unusual glycoforms with natriuretic peptides from P. aspidorhyncha and P. nuchaliscontaining O-linked trisaccharides with high homology to the glycosylated region of TNPc. 26632978 5 21 dep families 783:790 arg1 coverage 807:814 high sequence coverage 793:814 six toxin families; high sequence coverage highlighted subtle differences between sequences and intra and inter-specific variation between species 773:918 Integration of each venom proteome with the corresponding annotated reads identified 65 isoforms from six toxin families; high sequence coverage highlighted subtle differences between sequences and intra and inter-specific variation between species. 26632978 5 22 theme corresponding 715:727 arg1 annotated 729:737 the corresponding annotated 711:737 the corresponding annotated 711:737 Integration of each venom proteome with the corresponding annotated reads identified 65 isoforms from six toxin families; high sequence coverage highlighted subtle differences between sequences and intra and inter-specific variation between species. 26632978 11 23 theme venomous 2176:2183 arg1 snakes 2185:2190 other venomous snakes 2170:2190 other venomous snakes for a deeper understanding of venom composition, envenomation, venom evolution, 2170:2270 This generic strategy will provide invaluable information when applied to other venomous snakes for a deeper understanding of venom composition, envenomation, venom evolution, as well as identifying research tools and drug leads. 26632978 1 24 theme under-investigated 118:135 arg1 resource 137:144 an under-investigated resource 115:144 an under-investigated resource of novel bioactive peptides 115:172 Australian elapid venom remains an under-investigated resource of novel bioactive peptides. 26632978 11 25 theme research 2295:2302 arg1 tools 2304:2308 identifying research tools 2283:2308 identifying research tools 2283:2308 This generic strategy will provide invaluable information when applied to other venomous snakes for a deeper understanding of venom composition, envenomation, venom evolution, as well as identifying research tools and drug leads. 26632978 8 26 theme peptide 1428:1434 arg1 sequences 1436:1444 novel peptide sequences 1422:1444 novel peptide sequences from six bioactive peptide families 1422:1480 This study has revealed a wide range of novel peptide sequences from six bioactive peptide families and highlights the subtle differences between toxins in these closely related species. 26632978 7 27 theme evolutionary 1138:1149 arg1 assessments 1151:1161 Molecular evolutionary assessments 1128:1161 Molecular evolutionary assessments 1128:1161 Molecular evolutionary assessments indicated the accelerated evolution of all toxin families with the exception of both natriuretic peptides and P. aspidorhyncha PLA2s that were found to be evolutionarily constrained under purifying selection pressures. 26632978 2 28 theme brown 261:265 arg1 aspidorhyncha 286:298 aspidorhyncha 286:298 aspidorhyncha 286:298 In this study, the venom gland transcriptomes and proteomes of the Australian western brown snakes, Pseudonaja aspidorhyncha and Pseudonaja nuchalis, were compared to Pseudonaja textilis. 26632978 2 28 theme brown 261:265 arg1 nuchalis 315:322 nuchalis 315:322 nuchalis 315:322 In this study, the venom gland transcriptomes and proteomes of the Australian western brown snakes, Pseudonaja aspidorhyncha and Pseudonaja nuchalis, were compared to Pseudonaja textilis. 26632978 2 28 theme brown 261:265 arg1 snakes 267:272 the Australian western brown snakes 238:272 the Australian western brown snakes 238:272 In this study, the venom gland transcriptomes and proteomes of the Australian western brown snakes, Pseudonaja aspidorhyncha and Pseudonaja nuchalis, were compared to Pseudonaja textilis. 26632978 9 29 theme venomous 1654:1661 arg1 creatures 1663:1671 its venomous creatures 1650:1671 its venomous creatures 1650:1671 BIOLOGICAL SIGNIFICANCE Mining Australia's vastly untapped source of toxins from its venomous creatures has been significantly advanced by employing deep venomics methodology. 26632978 6 30 theme TNPc 1122:1125 arg1 region 1112:1117 the glycosylated region 1095:1117 the glycosylated region of TNPc 1095:1125 High quality MS/MS data identified unusual glycoforms with natriuretic peptides from P. aspidorhyncha and P. nuchaliscontaining O-linked trisaccharides with high homology to the glycosylated region of TNPc. 26632978 7 31 theme selection 1361:1369 arg1 pressures 1371:1379 selection pressures 1361:1379 selection pressures 1361:1379 Molecular evolutionary assessments indicated the accelerated evolution of all toxin families with the exception of both natriuretic peptides and P. aspidorhyncha PLA2s that were found to be evolutionarily constrained under purifying selection pressures. 26632978 5 32 theme inter-specific 879:892 arg1 variation 894:902 intra and inter-specific variation 869:902 variation 894:902 Integration of each venom proteome with the corresponding annotated reads identified 65 isoforms from six toxin families; high sequence coverage highlighted subtle differences between sequences and intra and inter-specific variation between species. 26632978 1 33 theme bioactive 155:163 arg1 peptides 165:172 novel bioactive peptides 149:172 novel bioactive peptides 149:172 Australian elapid venom remains an under-investigated resource of novel bioactive peptides. 26632978 8 34 theme bioactive 1455:1463 arg1 families 1473:1480 six bioactive peptide families 1451:1480 six bioactive peptide families 1451:1480 This study has revealed a wide range of novel peptide sequences from six bioactive peptide families and highlights the subtle differences between toxins in these closely related species. 26632978 3 35 theme deep 365:368 arg1 strategy 379:386 A deep venomics strategy 363:386 A deep venomics strategy incorporating high throughput 454 pyrosequencing gave a total of 200,911 raw 363:463 A deep venomics strategy incorporating high throughput 454 pyrosequencing gave a total of 200,911 raw reads for the three venoms. 26632978 5 36 theme toxin 777:781 arg1 families 783:790 six toxin families 773:790 six toxin families; high sequence coverage highlighted subtle differences between sequences and intra and inter-specific variation between species 773:918 Integration of each venom proteome with the corresponding annotated reads identified 65 isoforms from six toxin families; high sequence coverage highlighted subtle differences between sequences and intra and inter-specific variation between species. 26632978 0 37 theme genus 32:36 arg1 venomics 5:12 Deep venomics 0:12 Deep venomics of the Pseudonaja genus 0:36 Deep venomics of the Pseudonaja genus reveals inter- and intra-specific variation. 26632978 9 38 theme deep 1718:1721 arg1 methodology 1732:1742 deep venomics methodology 1718:1742 deep venomics methodology 1718:1742 BIOLOGICAL SIGNIFICANCE Mining Australia's vastly untapped source of toxins from its venomous creatures has been significantly advanced by employing deep venomics methodology. 26632978 3 39 theme high 402:405 arg1 throughput 407:416 high throughput 402:416 high throughput 454 pyrosequencing gave a total of 200,911 raw 402:463 A deep venomics strategy incorporating high throughput 454 pyrosequencing gave a total of 200,911 raw reads for the three venoms. 26632978 4 40 theme Subsequent 493:502 arg1 annotation 504:513 Subsequent annotation 493:513 Subsequent annotation 493:513 Subsequent annotation identified 5716 transcripts from 20 different toxin families with inter-specific variation between species observed in eight of the less abundant families. 26632978 0 41 theme intra-specific 57:70 arg1 variation 72:80 intra-specific variation 57:80 intra-specific variation 57:80 Deep venomics of the Pseudonaja genus reveals inter- and intra-specific variation. 26632978 8 42 theme subtle 1501:1506 arg1 differences 1508:1518 the subtle differences 1497:1518 the subtle differences between toxins in these closely related species 1497:1566 This study has revealed a wide range of novel peptide sequences from six bioactive peptide families and highlights the subtle differences between toxins in these closely related species. 26632978 5 43 theme intra 869:873 arg1 variation 894:902 intra and inter-specific variation 869:902 variation 894:902 Integration of each venom proteome with the corresponding annotated reads identified 65 isoforms from six toxin families; high sequence coverage highlighted subtle differences between sequences and intra and inter-specific variation between species. 26632978 2 44 theme Australian 242:251 arg1 aspidorhyncha 286:298 aspidorhyncha 286:298 aspidorhyncha 286:298 In this study, the venom gland transcriptomes and proteomes of the Australian western brown snakes, Pseudonaja aspidorhyncha and Pseudonaja nuchalis, were compared to Pseudonaja textilis. 26632978 2 44 theme Australian 242:251 arg1 nuchalis 315:322 nuchalis 315:322 nuchalis 315:322 In this study, the venom gland transcriptomes and proteomes of the Australian western brown snakes, Pseudonaja aspidorhyncha and Pseudonaja nuchalis, were compared to Pseudonaja textilis. 26632978 2 44 theme Australian 242:251 arg1 snakes 267:272 the Australian western brown snakes 238:272 the Australian western brown snakes 238:272 In this study, the venom gland transcriptomes and proteomes of the Australian western brown snakes, Pseudonaja aspidorhyncha and Pseudonaja nuchalis, were compared to Pseudonaja textilis. 26632978 1 45 theme elapid 94:99 arg1 venom 101:105 Australian elapid venom 83:105 Australian elapid venom 83:105 Australian elapid venom remains an under-investigated resource of novel bioactive peptides. 26632978 10 46 theme tandem 1879:1884 arg1 spectrometry 1891:1902 highly sensitive tandem mass spectrometry 1862:1902 highly sensitive tandem mass spectrometry 1862:1902 Technological advances in transcriptome analysis using next generation sequencing platforms and proteome analysis by highly sensitive tandem mass spectrometry allowed a more comprehensive interrogation of three underinvestigated brown snake (Pseudonaja) venoms uncovering many novel peptide sequences that are unique to these closely related species. 26632978 7 47 theme PLA2s 1290:1294 arg1 exception 1230:1238 the exception 1226:1238 the exception of both natriuretic peptides and P. aspidorhyncha PLA2s that were found to be evolutionarily constrained under purifying selection pressures 1226:1379 Molecular evolutionary assessments indicated the accelerated evolution of all toxin families with the exception of both natriuretic peptides and P. aspidorhyncha PLA2s that were found to be evolutionarily constrained under purifying selection pressures. 26632978 11 48 theme venom 2222:2226 arg1 envenomation 2241:2252 envenomation 2241:2252 envenomation 2241:2252 This generic strategy will provide invaluable information when applied to other venomous snakes for a deeper understanding of venom composition, envenomation, venom evolution, as well as identifying research tools and drug leads. 26632978 11 48 theme venom 2222:2226 arg1 evolution 2261:2269 venom evolution 2255:2269 venom evolution 2255:2269 This generic strategy will provide invaluable information when applied to other venomous snakes for a deeper understanding of venom composition, envenomation, venom evolution, as well as identifying research tools and drug leads. 26632978 11 48 theme venom 2222:2226 arg1 composition 2228:2238 venom composition 2222:2238 venom composition 2222:2238 This generic strategy will provide invaluable information when applied to other venomous snakes for a deeper understanding of venom composition, envenomation, venom evolution, as well as identifying research tools and drug leads. 26632978 0 49 theme Pseudonaja 21:30 arg1 genus 32:36 the Pseudonaja genus 17:36 the Pseudonaja genus 17:36 Deep venomics of the Pseudonaja genus reveals inter- and intra-specific variation. 26632978 7 50 theme P. 1273:1274 arg1 PLA2s 1290:1294 P. aspidorhyncha PLA2s 1273:1294 P. aspidorhyncha PLA2s 1273:1294 Molecular evolutionary assessments indicated the accelerated evolution of all toxin families with the exception of both natriuretic peptides and P. aspidorhyncha PLA2s that were found to be evolutionarily constrained under purifying selection pressures. 26632978 6 51 theme quality 926:932 arg1 data 940:943 High quality MS/MS data 921:943 High quality MS/MS data 921:943 High quality MS/MS data identified unusual glycoforms with natriuretic peptides from P. aspidorhyncha and P. nuchaliscontaining O-linked trisaccharides with high homology to the glycosylated region of TNPc. 26632978 9 52 from source 1628:1633 arg1 creatures 1663:1671 its venomous creatures 1650:1671 its venomous creatures 1650:1671 BIOLOGICAL SIGNIFICANCE Mining Australia's vastly untapped source of toxins from its venomous creatures has been significantly advanced by employing deep venomics methodology. 26632978 5 53 theme sequence 798:805 arg1 coverage 807:814 high sequence coverage 793:814 six toxin families; high sequence coverage highlighted subtle differences between sequences and intra and inter-specific variation between species 773:918 Integration of each venom proteome with the corresponding annotated reads identified 65 isoforms from six toxin families; high sequence coverage highlighted subtle differences between sequences and intra and inter-specific variation between species. 26632978 6 54 gly glycosylated 1099:1110 arg1 region 1112:1117 the glycosylated region 1095:1117 the glycosylated region of TNPc 1095:1125 High quality MS/MS data identified unusual glycoforms with natriuretic peptides from P. aspidorhyncha and P. nuchaliscontaining O-linked trisaccharides with high homology to the glycosylated region of TNPc. 26632978 7 55 theme peptides 1260:1267 arg1 exception 1230:1238 the exception 1226:1238 the exception of both natriuretic peptides and P. aspidorhyncha PLA2s that were found to be evolutionarily constrained under purifying selection pressures 1226:1379 Molecular evolutionary assessments indicated the accelerated evolution of all toxin families with the exception of both natriuretic peptides and P. aspidorhyncha PLA2s that were found to be evolutionarily constrained under purifying selection pressures. 26632978 4 56 theme toxin 561:565 arg1 families 567:574 20 different toxin families 548:574 20 different toxin families with inter-specific variation between species observed in eight of the less abundant families 548:668 Subsequent annotation identified 5716 transcripts from 20 different toxin families with inter-specific variation between species observed in eight of the less abundant families. 26632978 6 57 from nuchaliscontaining 1030:1047 arg1 peptides 992:999 natriuretic peptides 980:999 natriuretic peptides from P. aspidorhyncha and P. nuchaliscontaining O-linked trisaccharides with high homology to the glycosylated region of TNPc 980:1125 High quality MS/MS data identified unusual glycoforms with natriuretic peptides from P. aspidorhyncha and P. nuchaliscontaining O-linked trisaccharides with high homology to the glycosylated region of TNPc. 26632978 2 58 theme gland 200:204 arg1 transcriptomes 206:219 the venom gland transcriptomes 190:219 the venom gland transcriptomes 190:219 In this study, the venom gland transcriptomes and proteomes of the Australian western brown snakes, Pseudonaja aspidorhyncha and Pseudonaja nuchalis, were compared to Pseudonaja textilis. 26632978 11 59 theme composition 2228:2238 arg1 understanding 2205:2217 a deeper understanding 2196:2217 a deeper understanding of venom composition, envenomation, venom evolution, 2196:2270 This generic strategy will provide invaluable information when applied to other venomous snakes for a deeper understanding of venom composition, envenomation, venom evolution, as well as identifying research tools and drug leads. 26632978 10 60 theme comprehensive 1919:1931 arg1 interrogation 1933:1945 a more comprehensive interrogation 1912:1945 a more comprehensive interrogation of three underinvestigated brown snake (Pseudonaja) venoms uncovering many novel peptide sequences that are unique to these closely related species 1912:2093 Technological advances in transcriptome analysis using next generation sequencing platforms and proteome analysis by highly sensitive tandem mass spectrometry allowed a more comprehensive interrogation of three underinvestigated brown snake (Pseudonaja) venoms uncovering many novel peptide sequences that are unique to these closely related species. 26632978 8 61 from differences 1508:1518 arg1 species 1560:1566 these closely related species 1538:1566 these closely related species 1538:1566 This study has revealed a wide range of novel peptide sequences from six bioactive peptide families and highlights the subtle differences between toxins in these closely related species. 26632978 6 62 with glycoforms 964:973 arg1 peptides 992:999 natriuretic peptides 980:999 natriuretic peptides from P. aspidorhyncha and P. nuchaliscontaining O-linked trisaccharides with high homology to the glycosylated region of TNPc 980:1125 High quality MS/MS data identified unusual glycoforms with natriuretic peptides from P. aspidorhyncha and P. nuchaliscontaining O-linked trisaccharides with high homology to the glycosylated region of TNPc. 26632978 10 63 theme Technological 1745:1757 arg1 advances 1759:1766 Technological advances 1745:1766 Technological advances in transcriptome analysis using next generation sequencing platforms and proteome analysis by highly sensitive tandem mass spectrometry 1745:1902 Technological advances in transcriptome analysis using next generation sequencing platforms and proteome analysis by highly sensitive tandem mass spectrometry allowed a more comprehensive interrogation of three underinvestigated brown snake (Pseudonaja) venoms uncovering many novel peptide sequences that are unique to these closely related species. 26632978 5 64 theme proteome 697:704 arg1 Integration 671:681 Integration 671:681 Integration of each venom proteome with the corresponding annotated 671:737 Integration of each venom proteome with the corresponding annotated reads identified 65 isoforms from six toxin families; high sequence coverage highlighted subtle differences between sequences and intra and inter-specific variation between species. 26632978 11 65 theme invaluable 2131:2140 arg1 information 2142:2152 invaluable information 2131:2152 invaluable information when applied to other venomous snakes for a deeper understanding of venom composition, envenomation, venom evolution, as well as identifying research tools and drug leads 2131:2323 This generic strategy will provide invaluable information when applied to other venomous snakes for a deeper understanding of venom composition, envenomation, venom evolution, as well as identifying research tools and drug leads. 26632978 10 66 theme snake 1980:1984 arg1 venoms 1999:2004 three underinvestigated brown snake (Pseudonaja) venoms 1950:2004 three underinvestigated brown snake (Pseudonaja) venoms uncovering many novel peptide sequences that are unique to these closely related species 1950:2093 Technological advances in transcriptome analysis using next generation sequencing platforms and proteome analysis by highly sensitive tandem mass spectrometry allowed a more comprehensive interrogation of three underinvestigated brown snake (Pseudonaja) venoms uncovering many novel peptide sequences that are unique to these closely related species. 26632978 10 67 theme venoms 1999:2004 arg1 interrogation 1933:1945 a more comprehensive interrogation 1912:1945 a more comprehensive interrogation of three underinvestigated brown snake (Pseudonaja) venoms uncovering many novel peptide sequences that are unique to these closely related species 1912:2093 Technological advances in transcriptome analysis using next generation sequencing platforms and proteome analysis by highly sensitive tandem mass spectrometry allowed a more comprehensive interrogation of three underinvestigated brown snake (Pseudonaja) venoms uncovering many novel peptide sequences that are unique to these closely related species. 26632978 9 68 from creatures 1663:1671 arg1 toxins 1638:1643 toxins 1638:1643 toxins from its venomous creatures 1638:1671 BIOLOGICAL SIGNIFICANCE Mining Australia's vastly untapped source of toxins from its venomous creatures has been significantly advanced by employing deep venomics methodology. 26632978 9 68 from creatures 1663:1671 arg1 source 1628:1633 Australia's vastly untapped source 1600:1633 Australia's vastly untapped source of toxins from its venomous creatures 1600:1671 BIOLOGICAL SIGNIFICANCE Mining Australia's vastly untapped source of toxins from its venomous creatures has been significantly advanced by employing deep venomics methodology. 26632978 7 69 theme families 1212:1219 arg1 evolution 1189:1197 the accelerated evolution 1173:1197 the accelerated evolution of all toxin families with the exception of both natriuretic peptides and P. aspidorhyncha PLA2s that were found to be evolutionarily constrained under purifying selection pressures 1173:1379 Molecular evolutionary assessments indicated the accelerated evolution of all toxin families with the exception of both natriuretic peptides and P. aspidorhyncha PLA2s that were found to be evolutionarily constrained under purifying selection pressures. 26632978 10 70 theme underinvestigated 1956:1972 arg1 venoms 1999:2004 three underinvestigated brown snake (Pseudonaja) venoms 1950:2004 three underinvestigated brown snake (Pseudonaja) venoms uncovering many novel peptide sequences that are unique to these closely related species 1950:2093 Technological advances in transcriptome analysis using next generation sequencing platforms and proteome analysis by highly sensitive tandem mass spectrometry allowed a more comprehensive interrogation of three underinvestigated brown snake (Pseudonaja) venoms uncovering many novel peptide sequences that are unique to these closely related species. 26632978 11 71 theme deeper 2198:2203 arg1 understanding 2205:2217 a deeper understanding 2196:2217 a deeper understanding of venom composition, envenomation, venom evolution, 2196:2270 This generic strategy will provide invaluable information when applied to other venomous snakes for a deeper understanding of venom composition, envenomation, venom evolution, as well as identifying research tools and drug leads. 26632978 6 72 theme unusual 956:962 arg1 glycoforms 964:973 unusual glycoforms 956:973 unusual glycoforms with natriuretic peptides from P. aspidorhyncha and P. nuchaliscontaining O-linked trisaccharides with high homology to the glycosylated region of TNPc 956:1125 High quality MS/MS data identified unusual glycoforms with natriuretic peptides from P. aspidorhyncha and P. nuchaliscontaining O-linked trisaccharides with high homology to the glycosylated region of TNPc. 26632978 4 73 with families 567:574 arg1 variation 596:604 inter-specific variation 581:604 inter-specific variation between species observed in eight of the less abundant families 581:668 Subsequent annotation identified 5716 transcripts from 20 different toxin families with inter-specific variation between species observed in eight of the less abundant families. 26632978 6 74 theme high 1078:1081 arg1 homology 1083:1090 high homology 1078:1090 high homology to the glycosylated region of TNPc 1078:1125 High quality MS/MS data identified unusual glycoforms with natriuretic peptides from P. aspidorhyncha and P. nuchaliscontaining O-linked trisaccharides with high homology to the glycosylated region of TNPc. 26632978 10 75 theme Pseudonaja 1987:1996 arg1 venoms 1999:2004 three underinvestigated brown snake (Pseudonaja) venoms 1950:2004 three underinvestigated brown snake (Pseudonaja) venoms uncovering many novel peptide sequences that are unique to these closely related species 1950:2093 Technological advances in transcriptome analysis using next generation sequencing platforms and proteome analysis by highly sensitive tandem mass spectrometry allowed a more comprehensive interrogation of three underinvestigated brown snake (Pseudonaja) venoms uncovering many novel peptide sequences that are unique to these closely related species. 26632978 11 76 theme identifying 2283:2293 arg1 tools 2304:2308 identifying research tools 2283:2308 identifying research tools 2283:2308 This generic strategy will provide invaluable information when applied to other venomous snakes for a deeper understanding of venom composition, envenomation, venom evolution, as well as identifying research tools and drug leads. 26632978 4 77 theme families 661:668 arg1 families 661:668 the less abundant families 643:668 the less abundant families 643:668 Subsequent annotation identified 5716 transcripts from 20 different toxin families with inter-specific variation between species observed in eight of the less abundant families. 26632978 4 77 theme families 661:668 arg1 eight 634:638 eight 634:638 eight 634:638 Subsequent annotation identified 5716 transcripts from 20 different toxin families with inter-specific variation between species observed in eight of the less abundant families. 26632978 10 78 theme sequencing 1816:1825 arg1 platforms 1827:1835 next generation sequencing platforms 1800:1835 next generation sequencing platforms 1800:1835 Technological advances in transcriptome analysis using next generation sequencing platforms and proteome analysis by highly sensitive tandem mass spectrometry allowed a more comprehensive interrogation of three underinvestigated brown snake (Pseudonaja) venoms uncovering many novel peptide sequences that are unique to these closely related species. 26632978 10 79 theme peptide 2028:2034 arg1 sequences 2036:2044 many novel peptide sequences 2017:2044 many novel peptide sequences that are unique to these closely related species 2017:2093 Technological advances in transcriptome analysis using next generation sequencing platforms and proteome analysis by highly sensitive tandem mass spectrometry allowed a more comprehensive interrogation of three underinvestigated brown snake (Pseudonaja) venoms uncovering many novel peptide sequences that are unique to these closely related species. 26632978 10 80 theme next 1800:1803 arg1 platforms 1827:1835 next generation sequencing platforms 1800:1835 next generation sequencing platforms 1800:1835 Technological advances in transcriptome analysis using next generation sequencing platforms and proteome analysis by highly sensitive tandem mass spectrometry allowed a more comprehensive interrogation of three underinvestigated brown snake (Pseudonaja) venoms uncovering many novel peptide sequences that are unique to these closely related species. 26632978 10 81 theme many 2017:2020 arg1 sequences 2036:2044 many novel peptide sequences 2017:2044 many novel peptide sequences that are unique to these closely related species 2017:2093 Technological advances in transcriptome analysis using next generation sequencing platforms and proteome analysis by highly sensitive tandem mass spectrometry allowed a more comprehensive interrogation of three underinvestigated brown snake (Pseudonaja) venoms uncovering many novel peptide sequences that are unique to these closely related species. 26632978 9 82 theme toxins 1638:1643 arg1 source 1628:1633 Australia's vastly untapped source 1600:1633 Australia's vastly untapped source of toxins from its venomous creatures 1600:1671 BIOLOGICAL SIGNIFICANCE Mining Australia's vastly untapped source of toxins from its venomous creatures has been significantly advanced by employing deep venomics methodology. 26632978 7 83 theme Molecular 1128:1136 arg1 assessments 1151:1161 Molecular evolutionary assessments 1128:1161 Molecular evolutionary assessments 1128:1161 Molecular evolutionary assessments indicated the accelerated evolution of all toxin families with the exception of both natriuretic peptides and P. aspidorhyncha PLA2s that were found to be evolutionarily constrained under purifying selection pressures. 26632978 2 84 theme snakes 267:272 arg1 proteomes 225:233 proteomes 225:233 proteomes 225:233 In this study, the venom gland transcriptomes and proteomes of the Australian western brown snakes, Pseudonaja aspidorhyncha and Pseudonaja nuchalis, were compared to Pseudonaja textilis. 26632978 2 84 theme snakes 267:272 arg1 transcriptomes 206:219 the venom gland transcriptomes 190:219 the venom gland transcriptomes 190:219 In this study, the venom gland transcriptomes and proteomes of the Australian western brown snakes, Pseudonaja aspidorhyncha and Pseudonaja nuchalis, were compared to Pseudonaja textilis. 26632978 8 85 theme novel 1422:1426 arg1 sequences 1436:1444 novel peptide sequences 1422:1444 novel peptide sequences from six bioactive peptide families 1422:1480 This study has revealed a wide range of novel peptide sequences from six bioactive peptide families and highlights the subtle differences between toxins in these closely related species. 26632978 5 86 theme high 793:796 arg1 coverage 807:814 high sequence coverage 793:814 six toxin families; high sequence coverage highlighted subtle differences between sequences and intra and inter-specific variation between species 773:918 Integration of each venom proteome with the corresponding annotated reads identified 65 isoforms from six toxin families; high sequence coverage highlighted subtle differences between sequences and intra and inter-specific variation between species. 26632978 2 87 theme western 253:259 arg1 aspidorhyncha 286:298 aspidorhyncha 286:298 aspidorhyncha 286:298 In this study, the venom gland transcriptomes and proteomes of the Australian western brown snakes, Pseudonaja aspidorhyncha and Pseudonaja nuchalis, were compared to Pseudonaja textilis. 26632978 2 87 theme western 253:259 arg1 nuchalis 315:322 nuchalis 315:322 nuchalis 315:322 In this study, the venom gland transcriptomes and proteomes of the Australian western brown snakes, Pseudonaja aspidorhyncha and Pseudonaja nuchalis, were compared to Pseudonaja textilis. 26632978 2 87 theme western 253:259 arg1 snakes 267:272 the Australian western brown snakes 238:272 the Australian western brown snakes 238:272 In this study, the venom gland transcriptomes and proteomes of the Australian western brown snakes, Pseudonaja aspidorhyncha and Pseudonaja nuchalis, were compared to Pseudonaja textilis. 26632978 1 88 theme novel 149:153 arg1 peptides 165:172 novel bioactive peptides 149:172 novel bioactive peptides 149:172 Australian elapid venom remains an under-investigated resource of novel bioactive peptides. 26632978 8 89 theme sequences 1436:1444 arg1 range 1413:1417 a wide range 1406:1417 a wide range of novel peptide sequences from six bioactive peptide families 1406:1480 This study has revealed a wide range of novel peptide sequences from six bioactive peptide families and highlights the subtle differences between toxins in these closely related species. 26632978 5 90 dep reads 739:743 arg1 identified 745:754 identified 745:754 reads identified 65 isoforms from six toxin families; high sequence coverage highlighted subtle differences between sequences and intra and inter-specific variation between species 739:918 Integration of each venom proteome with the corresponding annotated reads identified 65 isoforms from six toxin families; high sequence coverage highlighted subtle differences between sequences and intra and inter-specific variation between species. 26632978 1 91 theme peptides 165:172 arg1 resource 137:144 an under-investigated resource 115:144 an under-investigated resource of novel bioactive peptides 115:172 Australian elapid venom remains an under-investigated resource of novel bioactive peptides. 26632978 6 92 theme glycosylated 1099:1110 arg1 region 1112:1117 the glycosylated region 1095:1117 the glycosylated region of TNPc 1095:1125 High quality MS/MS data identified unusual glycoforms with natriuretic peptides from P. aspidorhyncha and P. nuchaliscontaining O-linked trisaccharides with high homology to the glycosylated region of TNPc. 26632978 8 93 theme related 1552:1558 arg1 species 1560:1566 these closely related species 1538:1566 these closely related species 1538:1566 This study has revealed a wide range of novel peptide sequences from six bioactive peptide families and highlights the subtle differences between toxins in these closely related species. 26632978 3 94 theme venomics 370:377 arg1 strategy 379:386 A deep venomics strategy 363:386 A deep venomics strategy incorporating high throughput 454 pyrosequencing gave a total of 200,911 raw 363:463 A deep venomics strategy incorporating high throughput 454 pyrosequencing gave a total of 200,911 raw reads for the three venoms. 26632978 3 95 dep throughput 407:416 arg1 gave 437:440 gave 437:440 gave a total of 200,911 raw 437:463 A deep venomics strategy incorporating high throughput 454 pyrosequencing gave a total of 200,911 raw reads for the three venoms. 26632978 8 96 theme peptide 1465:1471 arg1 families 1473:1480 six bioactive peptide families 1451:1480 six bioactive peptide families 1451:1480 This study has revealed a wide range of novel peptide sequences from six bioactive peptide families and highlights the subtle differences between toxins in these closely related species. 26632978 8 97 from range 1413:1417 arg1 families 1473:1480 six bioactive peptide families 1451:1480 six bioactive peptide families 1451:1480 This study has revealed a wide range of novel peptide sequences from six bioactive peptide families and highlights the subtle differences between toxins in these closely related species. 26632978 3 98 theme raw 461:463 arg1 total 444:448 a total 442:448 a total of 200,911 raw 442:463 A deep venomics strategy incorporating high throughput 454 pyrosequencing gave a total of 200,911 raw reads for the three venoms. 26632978 1 99 theme Australian 83:92 arg1 venom 101:105 Australian elapid venom 83:105 Australian elapid venom 83:105 Australian elapid venom remains an under-investigated resource of novel bioactive peptides. 26632978 4 100 theme inter-specific 581:594 arg1 variation 596:604 inter-specific variation 581:604 inter-specific variation between species observed in eight of the less abundant families 581:668 Subsequent annotation identified 5716 transcripts from 20 different toxin families with inter-specific variation between species observed in eight of the less abundant families. 26632978 7 101 theme aspidorhyncha 1276:1288 arg1 PLA2s 1290:1294 P. aspidorhyncha PLA2s 1273:1294 P. aspidorhyncha PLA2s 1273:1294 Molecular evolutionary assessments indicated the accelerated evolution of all toxin families with the exception of both natriuretic peptides and P. aspidorhyncha PLA2s that were found to be evolutionarily constrained under purifying selection pressures. 26632978 10 102 theme related 2079:2085 arg1 species 2087:2093 these closely related species 2065:2093 these closely related species 2065:2093 Technological advances in transcriptome analysis using next generation sequencing platforms and proteome analysis by highly sensitive tandem mass spectrometry allowed a more comprehensive interrogation of three underinvestigated brown snake (Pseudonaja) venoms uncovering many novel peptide sequences that are unique to these closely related species. 26632978 10 103 theme sensitive 1869:1877 arg1 spectrometry 1891:1902 highly sensitive tandem mass spectrometry 1862:1902 highly sensitive tandem mass spectrometry 1862:1902 Technological advances in transcriptome analysis using next generation sequencing platforms and proteome analysis by highly sensitive tandem mass spectrometry allowed a more comprehensive interrogation of three underinvestigated brown snake (Pseudonaja) venoms uncovering many novel peptide sequences that are unique to these closely related species. 26632978 5 104 theme subtle 828:833 arg1 differences 835:845 subtle differences 828:845 subtle differences between sequences and intra and inter-specific variation between species 828:918 Integration of each venom proteome with the corresponding annotated reads identified 65 isoforms from six toxin families; high sequence coverage highlighted subtle differences between sequences and intra and inter-specific variation between species. 26632978 6 105 theme MS/MS 934:938 arg1 data 940:943 High quality MS/MS data 921:943 High quality MS/MS data 921:943 High quality MS/MS data identified unusual glycoforms with natriuretic peptides from P. aspidorhyncha and P. nuchaliscontaining O-linked trisaccharides with high homology to the glycosylated region of TNPc. 26632978 4 106 theme different 551:559 arg1 families 567:574 20 different toxin families 548:574 20 different toxin families with inter-specific variation between species observed in eight of the less abundant families 548:668 Subsequent annotation identified 5716 transcripts from 20 different toxin families with inter-specific variation between species observed in eight of the less abundant families. 26632978 7 107 theme natriuretic 1248:1258 arg1 peptides 1260:1267 natriuretic peptides 1248:1267 natriuretic peptides 1248:1267 Molecular evolutionary assessments indicated the accelerated evolution of all toxin families with the exception of both natriuretic peptides and P. aspidorhyncha PLA2s that were found to be evolutionarily constrained under purifying selection pressures. 26632978 6 108 theme High 921:924 arg1 data 940:943 High quality MS/MS data 921:943 High quality MS/MS data 921:943 High quality MS/MS data identified unusual glycoforms with natriuretic peptides from P. aspidorhyncha and P. nuchaliscontaining O-linked trisaccharides with high homology to the glycosylated region of TNPc. 26632978 5 109 with Integration 671:681 arg1 annotated 729:737 the corresponding annotated 711:737 the corresponding annotated 711:737 Integration of each venom proteome with the corresponding annotated reads identified 65 isoforms from six toxin families; high sequence coverage highlighted subtle differences between sequences and intra and inter-specific variation between species. 26632978 6 110 from aspidorhyncha 1009:1021 arg1 peptides 992:999 natriuretic peptides 980:999 natriuretic peptides from P. aspidorhyncha and P. nuchaliscontaining O-linked trisaccharides with high homology to the glycosylated region of TNPc 980:1125 High quality MS/MS data identified unusual glycoforms with natriuretic peptides from P. aspidorhyncha and P. nuchaliscontaining O-linked trisaccharides with high homology to the glycosylated region of TNPc. 26632978 2 111 theme Pseudonaja 342:351 arg1 textilis 353:360 Pseudonaja textilis 342:360 Pseudonaja textilis 342:360 In this study, the venom gland transcriptomes and proteomes of the Australian western brown snakes, Pseudonaja aspidorhyncha and Pseudonaja nuchalis, were compared to Pseudonaja textilis. 26632978 10 112 theme novel 2022:2026 arg1 sequences 2036:2044 many novel peptide sequences 2017:2044 many novel peptide sequences that are unique to these closely related species 2017:2093 Technological advances in transcriptome analysis using next generation sequencing platforms and proteome analysis by highly sensitive tandem mass spectrometry allowed a more comprehensive interrogation of three underinvestigated brown snake (Pseudonaja) venoms uncovering many novel peptide sequences that are unique to these closely related species. 26632978 7 113 with families 1212:1219 arg1 exception 1230:1238 the exception 1226:1238 the exception of both natriuretic peptides and P. aspidorhyncha PLA2s that were found to be evolutionarily constrained under purifying selection pressures 1226:1379 Molecular evolutionary assessments indicated the accelerated evolution of all toxin families with the exception of both natriuretic peptides and P. aspidorhyncha PLA2s that were found to be evolutionarily constrained under purifying selection pressures. 26632978 2 114 theme venom 194:198 arg1 transcriptomes 206:219 the venom gland transcriptomes 190:219 the venom gland transcriptomes 190:219 In this study, the venom gland transcriptomes and proteomes of the Australian western brown snakes, Pseudonaja aspidorhyncha and Pseudonaja nuchalis, were compared to Pseudonaja textilis. 26632978 4 115 located observed 622:629 arg2 species 614:620 species 614:620 species observed in eight of the less abundant families 614:668 Subsequent annotation identified 5716 transcripts from 20 different toxin families with inter-specific variation between species observed in eight of the less abundant families. 26632978 4 115 located observed 622:629 arg1 families 661:668 the less abundant families 643:668 the less abundant families 643:668 Subsequent annotation identified 5716 transcripts from 20 different toxin families with inter-specific variation between species observed in eight of the less abundant families. 26632978 4 115 located observed 622:629 arg1 eight 634:638 eight 634:638 eight 634:638 Subsequent annotation identified 5716 transcripts from 20 different toxin families with inter-specific variation between species observed in eight of the less abundant families. 26632978 10 116 theme mass 1886:1889 arg1 spectrometry 1891:1902 highly sensitive tandem mass spectrometry 1862:1902 highly sensitive tandem mass spectrometry 1862:1902 Technological advances in transcriptome analysis using next generation sequencing platforms and proteome analysis by highly sensitive tandem mass spectrometry allowed a more comprehensive interrogation of three underinvestigated brown snake (Pseudonaja) venoms uncovering many novel peptide sequences that are unique to these closely related species. 26632978 8 117 from families 1473:1480 arg1 range 1413:1417 a wide range 1406:1417 a wide range of novel peptide sequences from six bioactive peptide families 1406:1480 This study has revealed a wide range of novel peptide sequences from six bioactive peptide families and highlights the subtle differences between toxins in these closely related species. 26632978 8 117 from families 1473:1480 arg1 sequences 1436:1444 novel peptide sequences 1422:1444 novel peptide sequences from six bioactive peptide families 1422:1480 This study has revealed a wide range of novel peptide sequences from six bioactive peptide families and highlights the subtle differences between toxins in these closely related species. 26632978 10 118 theme proteome 1841:1848 arg1 analysis 1850:1857 proteome analysis 1841:1857 proteome analysis by highly sensitive tandem mass spectrometry 1841:1902 Technological advances in transcriptome analysis using next generation sequencing platforms and proteome analysis by highly sensitive tandem mass spectrometry allowed a more comprehensive interrogation of three underinvestigated brown snake (Pseudonaja) venoms uncovering many novel peptide sequences that are unique to these closely related species. 26632978 4 119 theme abundant 652:659 arg1 families 661:668 the less abundant families 643:668 the less abundant families 643:668 Subsequent annotation identified 5716 transcripts from 20 different toxin families with inter-specific variation between species observed in eight of the less abundant families. 26632978 11 120 theme generic 2101:2107 arg1 strategy 2109:2116 This generic strategy 2096:2116 This generic strategy 2096:2116 This generic strategy will provide invaluable information when applied to other venomous snakes for a deeper understanding of venom composition, envenomation, venom evolution, as well as identifying research tools and drug leads. 28679530 5 0 theme site-specific 1071:1083 arg1 profile 1094:1100 a site-specific N-glycan profile 1069:1100 a site-specific N-glycan profile 1069:1100 Our results highlight the importance of direct interactions between N-glycans and surface-exposed amino acids of glycoproteins on processing in the ER and the Golgi and the possibility of changing a site-specific N-glycan profile by modulating such interactions and thus the associated enzymatic fluxes. 28679530 5 1 theme associated 1147:1156 arg1 fluxes 1168:1173 the associated enzymatic fluxes 1143:1173 the associated enzymatic fluxes 1143:1173 Our results highlight the importance of direct interactions between N-glycans and surface-exposed amino acids of glycoproteins on processing in the ER and the Golgi and the possibility of changing a site-specific N-glycan profile by modulating such interactions and thus the associated enzymatic fluxes. 28679530 4 2 from bottlenecks 859:869 arg1 fluxes 839:844 the improved enzymatic fluxes 816:844 the improved enzymatic fluxes at enzymatic bottlenecks 816:869 By altering the primary sequence of PDI, we changed the glycan/protein interaction and thus the site-specific glycoprofile because of the improved enzymatic fluxes at enzymatic bottlenecks. 28679530 2 3 theme glycoprotein 465:476 arg1 PDI 388:390 PDI 388:390 PDI 388:390 PDI was produced as both secreted Sec-PDI and endoplasmic reticulum-retained glycoprotein (ER)-PDI, to study glycan processing by ER and Golgi resident enzymes. 28679530 2 3 theme glycoprotein 465:476 arg1 -PDI 482:485 endoplasmic reticulum-retained glycoprotein (ER)-PDI 434:485 endoplasmic reticulum-retained glycoprotein (ER)-PDI 434:485 PDI was produced as both secreted Sec-PDI and endoplasmic reticulum-retained glycoprotein (ER)-PDI, to study glycan processing by ER and Golgi resident enzymes. 28679530 5 4 theme enzymatic 1158:1166 arg1 fluxes 1168:1173 the associated enzymatic fluxes 1143:1173 the associated enzymatic fluxes 1143:1173 Our results highlight the importance of direct interactions between N-glycans and surface-exposed amino acids of glycoproteins on processing in the ER and the Golgi and the possibility of changing a site-specific N-glycan profile by modulating such interactions and thus the associated enzymatic fluxes. 28679530 1 5 theme oligosaccharide 176:190 arg1 processing 192:201 oligosaccharide processing 176:201 oligosaccharide processing 176:201 To study how the interaction between N-linked glycans and the surrounding amino acids influences oligosaccharide processing, we used protein disulfide isomerase (PDI), a glycoprotein bearing 5 N-glycosylation sites, as a model system and expressed it transiently in a Chinese hamster ovary (CHO)-S cell line. 28679530 5 6 theme N-glycan 1085:1092 arg1 profile 1094:1100 a site-specific N-glycan profile 1069:1100 a site-specific N-glycan profile 1069:1100 Our results highlight the importance of direct interactions between N-glycans and surface-exposed amino acids of glycoproteins on processing in the ER and the Golgi and the possibility of changing a site-specific N-glycan profile by modulating such interactions and thus the associated enzymatic fluxes. 28679530 5 7 theme such 1116:1119 arg1 interactions 1121:1132 such interactions 1116:1132 such interactions 1116:1132 Our results highlight the importance of direct interactions between N-glycans and surface-exposed amino acids of glycoproteins on processing in the ER and the Golgi and the possibility of changing a site-specific N-glycan profile by modulating such interactions and thus the associated enzymatic fluxes. 28679530 0 8 from Influence 0:8 arg1 heterogeneity 64:76 site-specific glycan heterogeneity 43:76 site-specific glycan heterogeneity 43:76 Influence of protein/glycan interaction on site-specific glycan heterogeneity. 28679530 5 9 theme glycoproteins 985:997 arg1 acids 976:980 N-glycans and surface-exposed amino acids 940:980 N-glycans and surface-exposed amino acids of glycoproteins 940:997 Our results highlight the importance of direct interactions between N-glycans and surface-exposed amino acids of glycoproteins on processing in the ER and the Golgi and the possibility of changing a site-specific N-glycan profile by modulating such interactions and thus the associated enzymatic fluxes. 28679530 6 10 theme primary 1189:1195 arg1 sequence 1205:1212 the primary protein sequence 1185:1212 the primary protein sequence 1185:1212 Altering the primary protein sequence can therefore be used to glycoengineer recombinant proteins.-Losfeld, M.-E., Scibona, E., Lin, C.-W., Villiger, T. K., Gauss, R., Morbidelli, M., Aebi, M. Influence of protein/glycan interaction on site-specific glycan heterogeneity. 28679530 1 11 theme Chinese 347:353 arg1 line 382:385 a Chinese hamster ovary (CHO)-S cell line 345:385 a Chinese hamster ovary (CHO)-S cell line 345:385 To study how the interaction between N-linked glycans and the surrounding amino acids influences oligosaccharide processing, we used protein disulfide isomerase (PDI), a glycoprotein bearing 5 N-glycosylation sites, as a model system and expressed it transiently in a Chinese hamster ovary (CHO)-S cell line. 28679530 4 12 theme glycan/protein 738:751 arg1 interaction 753:763 the glycan/protein interaction 734:763 the glycan/protein interaction and thus the site-specific glycoprofile because of the improved enzymatic fluxes at enzymatic bottlenecks 734:869 By altering the primary sequence of PDI, we changed the glycan/protein interaction and thus the site-specific glycoprofile because of the improved enzymatic fluxes at enzymatic bottlenecks. 28679530 1 13 theme N-glycosylation 272:286 arg1 sites 288:292 5 N-glycosylation sites 270:292 5 N-glycosylation sites 270:292 To study how the interaction between N-linked glycans and the surrounding amino acids influences oligosaccharide processing, we used protein disulfide isomerase (PDI), a glycoprotein bearing 5 N-glycosylation sites, as a model system and expressed it transiently in a Chinese hamster ovary (CHO)-S cell line. 28679530 2 14 dep ER 518:519 arg1 enzymes 540:546 resident enzymes 531:546 resident enzymes 531:546 PDI was produced as both secreted Sec-PDI and endoplasmic reticulum-retained glycoprotein (ER)-PDI, to study glycan processing by ER and Golgi resident enzymes. 28679530 1 15 theme hamster 355:361 arg1 line 382:385 a Chinese hamster ovary (CHO)-S cell line 345:385 a Chinese hamster ovary (CHO)-S cell line 345:385 To study how the interaction between N-linked glycans and the surrounding amino acids influences oligosaccharide processing, we used protein disulfide isomerase (PDI), a glycoprotein bearing 5 N-glycosylation sites, as a model system and expressed it transiently in a Chinese hamster ovary (CHO)-S cell line. 28679530 5 16 from importance 898:907 arg1 processing 1002:1011 processing 1002:1011 processing in the ER and the Golgi and the possibility of changing a site-specific N-glycan profile by modulating such interactions and thus the associated enzymatic fluxes 1002:1173 Our results highlight the importance of direct interactions between N-glycans and surface-exposed amino acids of glycoproteins on processing in the ER and the Golgi and the possibility of changing a site-specific N-glycan profile by modulating such interactions and thus the associated enzymatic fluxes. 28679530 5 17 theme N-glycans 940:948 arg1 acids 976:980 N-glycans and surface-exposed amino acids 940:980 N-glycans and surface-exposed amino acids of glycoproteins 940:997 Our results highlight the importance of direct interactions between N-glycans and surface-exposed amino acids of glycoproteins on processing in the ER and the Golgi and the possibility of changing a site-specific N-glycan profile by modulating such interactions and thus the associated enzymatic fluxes. 28679530 6 18 theme M. 1366:1367 arg1 Influence 1369:1377 recombinant proteins.-Losfeld, M.-E., Scibona, E., Lin, C.-W., Villiger, T. K., Gauss, R., Morbidelli, M., Aebi, M. Influence 1253:1377 recombinant proteins.-Losfeld, M.-E., Scibona, E., Lin, C.-W., Villiger, T. K., Gauss, R., Morbidelli, M., Aebi, M. Influence of protein/glycan interaction on site-specific glycan heterogeneity 1253:1445 Altering the primary protein sequence can therefore be used to glycoengineer recombinant proteins.-Losfeld, M.-E., Scibona, E., Lin, C.-W., Villiger, T. K., Gauss, R., Morbidelli, M., Aebi, M. Influence of protein/glycan interaction on site-specific glycan heterogeneity. 28679530 1 19 theme ovary 363:367 arg1 line 382:385 a Chinese hamster ovary (CHO)-S cell line 345:385 a Chinese hamster ovary (CHO)-S cell line 345:385 To study how the interaction between N-linked glycans and the surrounding amino acids influences oligosaccharide processing, we used protein disulfide isomerase (PDI), a glycoprotein bearing 5 N-glycosylation sites, as a model system and expressed it transiently in a Chinese hamster ovary (CHO)-S cell line. 28679530 2 20 theme reticulum-retained 446:463 arg1 ER 479:480 ER 479:480 ER 479:480 PDI was produced as both secreted Sec-PDI and endoplasmic reticulum-retained glycoprotein (ER)-PDI, to study glycan processing by ER and Golgi resident enzymes. 28679530 2 20 theme reticulum-retained 446:463 arg1 glycoprotein 465:476 endoplasmic reticulum-retained glycoprotein 434:476 endoplasmic reticulum-retained glycoprotein (ER)-PDI 434:485 PDI was produced as both secreted Sec-PDI and endoplasmic reticulum-retained glycoprotein (ER)-PDI, to study glycan processing by ER and Golgi resident enzymes. 28679530 6 21 theme protein 1197:1203 arg1 sequence 1205:1212 the primary protein sequence 1185:1212 the primary protein sequence 1185:1212 Altering the primary protein sequence can therefore be used to glycoengineer recombinant proteins.-Losfeld, M.-E., Scibona, E., Lin, C.-W., Villiger, T. K., Gauss, R., Morbidelli, M., Aebi, M. Influence of protein/glycan interaction on site-specific glycan heterogeneity. 28679530 6 22 theme protein/glycan 1382:1395 arg1 interaction 1397:1407 protein/glycan interaction 1382:1407 protein/glycan interaction 1382:1407 Altering the primary protein sequence can therefore be used to glycoengineer recombinant proteins.-Losfeld, M.-E., Scibona, E., Lin, C.-W., Villiger, T. K., Gauss, R., Morbidelli, M., Aebi, M. Influence of protein/glycan interaction on site-specific glycan heterogeneity. 28679530 2 23 theme secreted 413:420 arg1 PDI 388:390 PDI 388:390 PDI 388:390 PDI was produced as both secreted Sec-PDI and endoplasmic reticulum-retained glycoprotein (ER)-PDI, to study glycan processing by ER and Golgi resident enzymes. 28679530 2 23 theme secreted 413:420 arg1 Sec-PDI 422:428 secreted Sec-PDI 413:428 secreted Sec-PDI 413:428 PDI was produced as both secreted Sec-PDI and endoplasmic reticulum-retained glycoprotein (ER)-PDI, to study glycan processing by ER and Golgi resident enzymes. 28679530 1 24 gly glycoprotein 249:260 arg1 isomerase 230:238 protein disulfide isomerase 212:238 protein disulfide isomerase (PDI) 212:244 To study how the interaction between N-linked glycans and the surrounding amino acids influences oligosaccharide processing, we used protein disulfide isomerase (PDI), a glycoprotein bearing 5 N-glycosylation sites, as a model system and expressed it transiently in a Chinese hamster ovary (CHO)-S cell line. 28679530 1 24 gly glycoprotein 249:260 arg1 glycoprotein 249:260 a glycoprotein 247:260 a glycoprotein bearing 5 N-glycosylation sites 247:292 To study how the interaction between N-linked glycans and the surrounding amino acids influences oligosaccharide processing, we used protein disulfide isomerase (PDI), a glycoprotein bearing 5 N-glycosylation sites, as a model system and expressed it transiently in a Chinese hamster ovary (CHO)-S cell line. 28679530 5 25 theme surface-exposed 954:968 arg1 acids 976:980 N-glycans and surface-exposed amino acids 940:980 N-glycans and surface-exposed amino acids of glycoproteins 940:997 Our results highlight the importance of direct interactions between N-glycans and surface-exposed amino acids of glycoproteins on processing in the ER and the Golgi and the possibility of changing a site-specific N-glycan profile by modulating such interactions and thus the associated enzymatic fluxes. 28679530 6 26 theme site-specific 1412:1424 arg1 heterogeneity 1433:1445 site-specific glycan heterogeneity 1412:1445 site-specific glycan heterogeneity 1412:1445 Altering the primary protein sequence can therefore be used to glycoengineer recombinant proteins.-Losfeld, M.-E., Scibona, E., Lin, C.-W., Villiger, T. K., Gauss, R., Morbidelli, M., Aebi, M. Influence of protein/glycan interaction on site-specific glycan heterogeneity. 28679530 4 27 theme enzymatic 849:857 arg1 bottlenecks 859:869 enzymatic bottlenecks 849:869 enzymatic bottlenecks 849:869 By altering the primary sequence of PDI, we changed the glycan/protein interaction and thus the site-specific glycoprofile because of the improved enzymatic fluxes at enzymatic bottlenecks. 28679530 1 28 gly N-glycosylation 272:286 arg2 sites 288:292 5 N-glycosylation sites 270:292 5 N-glycosylation sites 270:292 To study how the interaction between N-linked glycans and the surrounding amino acids influences oligosaccharide processing, we used protein disulfide isomerase (PDI), a glycoprotein bearing 5 N-glycosylation sites, as a model system and expressed it transiently in a Chinese hamster ovary (CHO)-S cell line. 28679530 1 28 gly N-glycosylation 272:286 arg2 5 270:270 5 270:270 5 270:270 To study how the interaction between N-linked glycans and the surrounding amino acids influences oligosaccharide processing, we used protein disulfide isomerase (PDI), a glycoprotein bearing 5 N-glycosylation sites, as a model system and expressed it transiently in a Chinese hamster ovary (CHO)-S cell line. 28679530 5 29 theme amino 970:974 arg1 acids 976:980 N-glycans and surface-exposed amino acids 940:980 N-glycans and surface-exposed amino acids of glycoproteins 940:997 Our results highlight the importance of direct interactions between N-glycans and surface-exposed amino acids of glycoproteins on processing in the ER and the Golgi and the possibility of changing a site-specific N-glycan profile by modulating such interactions and thus the associated enzymatic fluxes. 28679530 5 30 theme direct 912:917 arg1 interactions 919:930 direct interactions 912:930 direct interactions between N-glycans and surface-exposed amino acids of glycoproteins 912:997 Our results highlight the importance of direct interactions between N-glycans and surface-exposed amino acids of glycoproteins on processing in the ER and the Golgi and the possibility of changing a site-specific N-glycan profile by modulating such interactions and thus the associated enzymatic fluxes. 28679530 0 31 theme interaction 28:38 arg1 Influence 0:8 Influence 0:8 Influence of protein/glycan interaction on site-specific glycan heterogeneity. 0:77 Influence of protein/glycan interaction on site-specific glycan heterogeneity. 28679530 4 32 theme improved 820:827 arg1 fluxes 839:844 the improved enzymatic fluxes 816:844 the improved enzymatic fluxes at enzymatic bottlenecks 816:869 By altering the primary sequence of PDI, we changed the glycan/protein interaction and thus the site-specific glycoprofile because of the improved enzymatic fluxes at enzymatic bottlenecks. 28679530 2 33 gly glycoprotein 465:476 arg1 ER 479:480 ER 479:480 ER 479:480 PDI was produced as both secreted Sec-PDI and endoplasmic reticulum-retained glycoprotein (ER)-PDI, to study glycan processing by ER and Golgi resident enzymes. 28679530 2 33 gly glycoprotein 465:476 arg1 glycoprotein 465:476 endoplasmic reticulum-retained glycoprotein 434:476 endoplasmic reticulum-retained glycoprotein (ER)-PDI 434:485 PDI was produced as both secreted Sec-PDI and endoplasmic reticulum-retained glycoprotein (ER)-PDI, to study glycan processing by ER and Golgi resident enzymes. 28679530 1 34 theme protein 212:218 arg1 system 306:311 a model system 298:311 a model system 298:311 To study how the interaction between N-linked glycans and the surrounding amino acids influences oligosaccharide processing, we used protein disulfide isomerase (PDI), a glycoprotein bearing 5 N-glycosylation sites, as a model system and expressed it transiently in a Chinese hamster ovary (CHO)-S cell line. 28679530 1 34 theme protein 212:218 arg1 PDI 241:243 PDI 241:243 PDI 241:243 To study how the interaction between N-linked glycans and the surrounding amino acids influences oligosaccharide processing, we used protein disulfide isomerase (PDI), a glycoprotein bearing 5 N-glycosylation sites, as a model system and expressed it transiently in a Chinese hamster ovary (CHO)-S cell line. 28679530 1 34 theme protein 212:218 arg1 isomerase 230:238 protein disulfide isomerase 212:238 protein disulfide isomerase (PDI) 212:244 To study how the interaction between N-linked glycans and the surrounding amino acids influences oligosaccharide processing, we used protein disulfide isomerase (PDI), a glycoprotein bearing 5 N-glycosylation sites, as a model system and expressed it transiently in a Chinese hamster ovary (CHO)-S cell line. 28679530 1 34 theme protein 212:218 arg1 glycoprotein 249:260 a glycoprotein 247:260 a glycoprotein bearing 5 N-glycosylation sites 247:292 To study how the interaction between N-linked glycans and the surrounding amino acids influences oligosaccharide processing, we used protein disulfide isomerase (PDI), a glycoprotein bearing 5 N-glycosylation sites, as a model system and expressed it transiently in a Chinese hamster ovary (CHO)-S cell line. 28679530 0 35 theme protein/glycan 13:26 arg1 interaction 28:38 protein/glycan interaction 13:38 protein/glycan interaction 13:38 Influence of protein/glycan interaction on site-specific glycan heterogeneity. 28679530 6 36 dep M. 1366:1367 arg1 M.-E. 1284:1288 M.-E. 1284:1288 M.-E. 1284:1288 Altering the primary protein sequence can therefore be used to glycoengineer recombinant proteins.-Losfeld, M.-E., Scibona, E., Lin, C.-W., Villiger, T. K., Gauss, R., Morbidelli, M., Aebi, M. Influence of protein/glycan interaction on site-specific glycan heterogeneity. 28679530 1 37 theme CHO 370:372 arg1 line 382:385 a Chinese hamster ovary (CHO)-S cell line 345:385 a Chinese hamster ovary (CHO)-S cell line 345:385 To study how the interaction between N-linked glycans and the surrounding amino acids influences oligosaccharide processing, we used protein disulfide isomerase (PDI), a glycoprotein bearing 5 N-glycosylation sites, as a model system and expressed it transiently in a Chinese hamster ovary (CHO)-S cell line. 28679530 1 38 theme N-linked 116:123 arg1 glycans 125:131 N-linked glycans 116:131 N-linked glycans 116:131 To study how the interaction between N-linked glycans and the surrounding amino acids influences oligosaccharide processing, we used protein disulfide isomerase (PDI), a glycoprotein bearing 5 N-glycosylation sites, as a model system and expressed it transiently in a Chinese hamster ovary (CHO)-S cell line. 28679530 1 39 theme disulfide 220:228 arg1 system 306:311 a model system 298:311 a model system 298:311 To study how the interaction between N-linked glycans and the surrounding amino acids influences oligosaccharide processing, we used protein disulfide isomerase (PDI), a glycoprotein bearing 5 N-glycosylation sites, as a model system and expressed it transiently in a Chinese hamster ovary (CHO)-S cell line. 28679530 1 39 theme disulfide 220:228 arg1 PDI 241:243 PDI 241:243 PDI 241:243 To study how the interaction between N-linked glycans and the surrounding amino acids influences oligosaccharide processing, we used protein disulfide isomerase (PDI), a glycoprotein bearing 5 N-glycosylation sites, as a model system and expressed it transiently in a Chinese hamster ovary (CHO)-S cell line. 28679530 1 39 theme disulfide 220:228 arg1 isomerase 230:238 protein disulfide isomerase 212:238 protein disulfide isomerase (PDI) 212:244 To study how the interaction between N-linked glycans and the surrounding amino acids influences oligosaccharide processing, we used protein disulfide isomerase (PDI), a glycoprotein bearing 5 N-glycosylation sites, as a model system and expressed it transiently in a Chinese hamster ovary (CHO)-S cell line. 28679530 1 39 theme disulfide 220:228 arg1 glycoprotein 249:260 a glycoprotein 247:260 a glycoprotein bearing 5 N-glycosylation sites 247:292 To study how the interaction between N-linked glycans and the surrounding amino acids influences oligosaccharide processing, we used protein disulfide isomerase (PDI), a glycoprotein bearing 5 N-glycosylation sites, as a model system and expressed it transiently in a Chinese hamster ovary (CHO)-S cell line. 28679530 0 40 theme site-specific 43:55 arg1 heterogeneity 64:76 site-specific glycan heterogeneity 43:76 site-specific glycan heterogeneity 43:76 Influence of protein/glycan interaction on site-specific glycan heterogeneity. 28679530 3 41 theme site-specific 562:574 arg1 profiles 590:597 Quantitative site-specific glycosylation profiles 549:597 Quantitative site-specific glycosylation profiles 549:597 Quantitative site-specific glycosylation profiles were obtained, and flux analysis enabled modeling site-specific glycan processing. 28679530 2 42 theme endoplasmic 434:444 arg1 ER 479:480 ER 479:480 ER 479:480 PDI was produced as both secreted Sec-PDI and endoplasmic reticulum-retained glycoprotein (ER)-PDI, to study glycan processing by ER and Golgi resident enzymes. 28679530 2 42 theme endoplasmic 434:444 arg1 glycoprotein 465:476 endoplasmic reticulum-retained glycoprotein 434:476 endoplasmic reticulum-retained glycoprotein (ER)-PDI 434:485 PDI was produced as both secreted Sec-PDI and endoplasmic reticulum-retained glycoprotein (ER)-PDI, to study glycan processing by ER and Golgi resident enzymes. 28679530 1 43 theme model 300:304 arg1 system 306:311 a model system 298:311 a model system 298:311 To study how the interaction between N-linked glycans and the surrounding amino acids influences oligosaccharide processing, we used protein disulfide isomerase (PDI), a glycoprotein bearing 5 N-glycosylation sites, as a model system and expressed it transiently in a Chinese hamster ovary (CHO)-S cell line. 28679530 1 43 theme model 300:304 arg1 isomerase 230:238 protein disulfide isomerase 212:238 protein disulfide isomerase (PDI) 212:244 To study how the interaction between N-linked glycans and the surrounding amino acids influences oligosaccharide processing, we used protein disulfide isomerase (PDI), a glycoprotein bearing 5 N-glycosylation sites, as a model system and expressed it transiently in a Chinese hamster ovary (CHO)-S cell line. 28679530 2 44 theme glycan 497:502 arg1 processing 504:513 glycan processing 497:513 glycan processing 497:513 PDI was produced as both secreted Sec-PDI and endoplasmic reticulum-retained glycoprotein (ER)-PDI, to study glycan processing by ER and Golgi resident enzymes. 28679530 3 45 theme glycosylation 576:588 arg1 profiles 590:597 Quantitative site-specific glycosylation profiles 549:597 Quantitative site-specific glycosylation profiles 549:597 Quantitative site-specific glycosylation profiles were obtained, and flux analysis enabled modeling site-specific glycan processing. 28679530 5 46 gly glycoproteins 985:997 arg1 glycoproteins 985:997 glycoproteins 985:997 glycoproteins 985:997 Our results highlight the importance of direct interactions between N-glycans and surface-exposed amino acids of glycoproteins on processing in the ER and the Golgi and the possibility of changing a site-specific N-glycan profile by modulating such interactions and thus the associated enzymatic fluxes. 28679530 1 47 theme cell 377:380 arg1 line 382:385 a Chinese hamster ovary (CHO)-S cell line 345:385 a Chinese hamster ovary (CHO)-S cell line 345:385 To study how the interaction between N-linked glycans and the surrounding amino acids influences oligosaccharide processing, we used protein disulfide isomerase (PDI), a glycoprotein bearing 5 N-glycosylation sites, as a model system and expressed it transiently in a Chinese hamster ovary (CHO)-S cell line. 28679530 4 48 theme enzymatic 829:837 arg1 fluxes 839:844 the improved enzymatic fluxes 816:844 the improved enzymatic fluxes at enzymatic bottlenecks 816:869 By altering the primary sequence of PDI, we changed the glycan/protein interaction and thus the site-specific glycoprofile because of the improved enzymatic fluxes at enzymatic bottlenecks. 28679530 5 49 theme interactions 919:930 arg1 importance 898:907 the importance 894:907 the importance of direct interactions between N-glycans and surface-exposed amino acids of glycoproteins on processing in the ER and the Golgi and the possibility of changing a site-specific N-glycan profile by modulating such interactions and thus the associated enzymatic fluxes 894:1173 Our results highlight the importance of direct interactions between N-glycans and surface-exposed amino acids of glycoproteins on processing in the ER and the Golgi and the possibility of changing a site-specific N-glycan profile by modulating such interactions and thus the associated enzymatic fluxes. 28679530 0 50 theme glycan 57:62 arg1 heterogeneity 64:76 site-specific glycan heterogeneity 43:76 site-specific glycan heterogeneity 43:76 Influence of protein/glycan interaction on site-specific glycan heterogeneity. 28679530 4 51 theme fluxes 839:844 arg1 glycoprofile 792:803 glycoprofile 792:803 glycoprofile 792:803 By altering the primary sequence of PDI, we changed the glycan/protein interaction and thus the site-specific glycoprofile because of the improved enzymatic fluxes at enzymatic bottlenecks. 28679530 2 52 theme resident 531:538 arg1 enzymes 540:546 resident enzymes 531:546 resident enzymes 531:546 PDI was produced as both secreted Sec-PDI and endoplasmic reticulum-retained glycoprotein (ER)-PDI, to study glycan processing by ER and Golgi resident enzymes. 28679530 3 53 theme glycan 663:668 arg1 processing 670:679 modeling site-specific glycan processing 640:679 modeling site-specific glycan processing 640:679 Quantitative site-specific glycosylation profiles were obtained, and flux analysis enabled modeling site-specific glycan processing. 28679530 3 54 theme Quantitative 549:560 arg1 profiles 590:597 Quantitative site-specific glycosylation profiles 549:597 Quantitative site-specific glycosylation profiles 549:597 Quantitative site-specific glycosylation profiles were obtained, and flux analysis enabled modeling site-specific glycan processing. 28679530 4 55 theme primary 698:704 arg1 sequence 706:713 the primary sequence 694:713 the primary sequence of PDI 694:720 By altering the primary sequence of PDI, we changed the glycan/protein interaction and thus the site-specific glycoprofile because of the improved enzymatic fluxes at enzymatic bottlenecks. 28679530 6 56 theme recombinant 1253:1263 arg1 Influence 1369:1377 recombinant proteins.-Losfeld, M.-E., Scibona, E., Lin, C.-W., Villiger, T. K., Gauss, R., Morbidelli, M., Aebi, M. Influence 1253:1377 recombinant proteins.-Losfeld, M.-E., Scibona, E., Lin, C.-W., Villiger, T. K., Gauss, R., Morbidelli, M., Aebi, M. Influence of protein/glycan interaction on site-specific glycan heterogeneity 1253:1445 Altering the primary protein sequence can therefore be used to glycoengineer recombinant proteins.-Losfeld, M.-E., Scibona, E., Lin, C.-W., Villiger, T. K., Gauss, R., Morbidelli, M., Aebi, M. Influence of protein/glycan interaction on site-specific glycan heterogeneity. 28679530 5 57 dep interactions 1121:1132 arg1 fluxes 1168:1173 the associated enzymatic fluxes 1143:1173 the associated enzymatic fluxes 1143:1173 Our results highlight the importance of direct interactions between N-glycans and surface-exposed amino acids of glycoproteins on processing in the ER and the Golgi and the possibility of changing a site-specific N-glycan profile by modulating such interactions and thus the associated enzymatic fluxes. 28679530 1 58 used used 207:210 arg2 we 204:205 we 204:205 we 204:205 To study how the interaction between N-linked glycans and the surrounding amino acids influences oligosaccharide processing, we used protein disulfide isomerase (PDI), a glycoprotein bearing 5 N-glycosylation sites, as a model system and expressed it transiently in a Chinese hamster ovary (CHO)-S cell line. 28679530 3 59 theme flux 618:621 arg1 analysis 623:630 flux analysis 618:630 flux analysis 618:630 Quantitative site-specific glycosylation profiles were obtained, and flux analysis enabled modeling site-specific glycan processing. 28679530 3 60 theme modeling 640:647 arg1 processing 670:679 modeling site-specific glycan processing 640:679 modeling site-specific glycan processing 640:679 Quantitative site-specific glycosylation profiles were obtained, and flux analysis enabled modeling site-specific glycan processing. 28679530 1 61 theme surrounding 141:151 arg1 acids 159:163 the surrounding amino acids 137:163 the surrounding amino acids 137:163 To study how the interaction between N-linked glycans and the surrounding amino acids influences oligosaccharide processing, we used protein disulfide isomerase (PDI), a glycoprotein bearing 5 N-glycosylation sites, as a model system and expressed it transiently in a Chinese hamster ovary (CHO)-S cell line. 28679530 4 62 theme PDI 718:720 arg1 sequence 706:713 the primary sequence 694:713 the primary sequence of PDI 694:720 By altering the primary sequence of PDI, we changed the glycan/protein interaction and thus the site-specific glycoprofile because of the improved enzymatic fluxes at enzymatic bottlenecks. 28679530 3 63 theme site-specific 649:661 arg1 processing 670:679 modeling site-specific glycan processing 640:679 modeling site-specific glycan processing 640:679 Quantitative site-specific glycosylation profiles were obtained, and flux analysis enabled modeling site-specific glycan processing. 28679530 1 64 theme amino 153:157 arg1 acids 159:163 the surrounding amino acids 137:163 the surrounding amino acids 137:163 To study how the interaction between N-linked glycans and the surrounding amino acids influences oligosaccharide processing, we used protein disulfide isomerase (PDI), a glycoprotein bearing 5 N-glycosylation sites, as a model system and expressed it transiently in a Chinese hamster ovary (CHO)-S cell line. 28679530 6 65 from Influence 1369:1377 arg1 heterogeneity 1433:1445 site-specific glycan heterogeneity 1412:1445 site-specific glycan heterogeneity 1412:1445 Altering the primary protein sequence can therefore be used to glycoengineer recombinant proteins.-Losfeld, M.-E., Scibona, E., Lin, C.-W., Villiger, T. K., Gauss, R., Morbidelli, M., Aebi, M. Influence of protein/glycan interaction on site-specific glycan heterogeneity. 28679530 1 66 link N-linked 116:123 arg1 glycans 125:131 N-linked glycans 116:131 N-linked glycans 116:131 To study how the interaction between N-linked glycans and the surrounding amino acids influences oligosaccharide processing, we used protein disulfide isomerase (PDI), a glycoprotein bearing 5 N-glycosylation sites, as a model system and expressed it transiently in a Chinese hamster ovary (CHO)-S cell line. 28679530 6 67 theme interaction 1397:1407 arg1 Influence 1369:1377 recombinant proteins.-Losfeld, M.-E., Scibona, E., Lin, C.-W., Villiger, T. K., Gauss, R., Morbidelli, M., Aebi, M. Influence 1253:1377 recombinant proteins.-Losfeld, M.-E., Scibona, E., Lin, C.-W., Villiger, T. K., Gauss, R., Morbidelli, M., Aebi, M. Influence of protein/glycan interaction on site-specific glycan heterogeneity 1253:1445 Altering the primary protein sequence can therefore be used to glycoengineer recombinant proteins.-Losfeld, M.-E., Scibona, E., Lin, C.-W., Villiger, T. K., Gauss, R., Morbidelli, M., Aebi, M. Influence of protein/glycan interaction on site-specific glycan heterogeneity. 28679530 6 68 theme glycan 1426:1431 arg1 heterogeneity 1433:1445 site-specific glycan heterogeneity 1412:1445 site-specific glycan heterogeneity 1412:1445 Altering the primary protein sequence can therefore be used to glycoengineer recombinant proteins.-Losfeld, M.-E., Scibona, E., Lin, C.-W., Villiger, T. K., Gauss, R., Morbidelli, M., Aebi, M. Influence of protein/glycan interaction on site-specific glycan heterogeneity. 28679530 5 69 from processing 1002:1011 arg1 ER 1020:1021 ER 1020:1021 ER 1020:1021 Our results highlight the importance of direct interactions between N-glycans and surface-exposed amino acids of glycoproteins on processing in the ER and the Golgi and the possibility of changing a site-specific N-glycan profile by modulating such interactions and thus the associated enzymatic fluxes. 28679530 5 69 from processing 1002:1011 arg1 Golgi 1031:1035 the Golgi 1027:1035 the Golgi 1027:1035 Our results highlight the importance of direct interactions between N-glycans and surface-exposed amino acids of glycoproteins on processing in the ER and the Golgi and the possibility of changing a site-specific N-glycan profile by modulating such interactions and thus the associated enzymatic fluxes. 28679530 5 69 from processing 1002:1011 arg1 possibility 1045:1055 the possibility 1041:1055 the possibility of changing a site-specific N-glycan profile by modulating such interactions and thus the associated enzymatic fluxes 1041:1173 Our results highlight the importance of direct interactions between N-glycans and surface-exposed amino acids of glycoproteins on processing in the ER and the Golgi and the possibility of changing a site-specific N-glycan profile by modulating such interactions and thus the associated enzymatic fluxes. 28198557 7 0 located found 920:924 arg2 variants 906:913 C. CCR5-using variants 892:913 C. CCR5-using variants 892:913 Two hundred and thirty-seven (89%) children were infected with CRF01_AE, 29 (11%) were subtype B and 1 was subtype C. CCR5-using variants were found in 148 (55%) children and CXCR4-using variants were observed in 119 (45%) children. 28198557 7 0 located found 920:924 arg1 children 939:946 148 (55%) children 929:946 148 (55%) children 929:946 Two hundred and thirty-seven (89%) children were infected with CRF01_AE, 29 (11%) were subtype B and 1 was subtype C. CCR5-using variants were found in 148 (55%) children and CXCR4-using variants were observed in 119 (45%) children. 28198557 7 0 located found 920:924 arg1 % 936:936 55% 934:936 55% 934:936 Two hundred and thirty-seven (89%) children were infected with CRF01_AE, 29 (11%) were subtype B and 1 was subtype C. CCR5-using variants were found in 148 (55%) children and CXCR4-using variants were observed in 119 (45%) children. 28198557 0 1 from usage 17:21 arg1 children 52:59 perinatally infected Thai children 26:59 perinatally infected Thai children 26:59 HIV-1 coreceptor usage in perinatally infected Thai children. 28198557 10 2 theme CCR5 1387:1390 arg1 family 1403:1408 CCR5 antagonist family 1387:1408 CCR5 antagonist family 1387:1408 This evidence showed that X4 viruses can be highly observed at an early age of children which has important clinical implications and may limit usage of CCR5 antagonist family. 28198557 1 3 from usage 79:83 arg1 children 88:95 children 88:95 children who were born to HIV-1 infected mothers in Thailand 88:147 HIV-1 coreceptor usage in children who were born to HIV-1 infected mothers in Thailand is not well characterized. 28198557 4 4 theme DNA 563:565 arg1 sequencing 567:576 DNA sequencing 563:576 DNA sequencing 563:576 Genotypic tropism testing was performed based on amplification of the V3 region in a triplicate nested-PCR following by DNA sequencing. 28198557 8 5 theme coreceptor 1040:1049 arg1 usage 1051:1055 coreceptor usage 1040:1055 coreceptor usage 1040:1055 No significant differences in coreceptor usage and age, gender, signs of HIV infection, children's or maternal ARV receiving were observed. 28198557 4 6 from amplification 492:504 arg1 nested-PCR 539:548 a triplicate nested-PCR 526:548 a triplicate nested-PCR following by DNA sequencing 526:576 Genotypic tropism testing was performed based on amplification of the V3 region in a triplicate nested-PCR following by DNA sequencing. 28198557 5 7 theme HIV-1 579:583 arg1 usage 596:600 HIV-1 coreceptor usage 579:600 HIV-1 coreceptor usage 579:600 HIV-1 coreceptor usage was determined using Geno2pheno[coreceptor] with a false positive rate of 10%. 28198557 8 8 theme maternal 1112:1119 arg1 ARV 1121:1123 maternal ARV 1112:1123 maternal ARV 1112:1123 No significant differences in coreceptor usage and age, gender, signs of HIV infection, children's or maternal ARV receiving were observed. 28198557 10 9 located observed 1285:1292 arg2 viruses 1263:1269 X4 viruses 1260:1269 X4 viruses 1260:1269 This evidence showed that X4 viruses can be highly observed at an early age of children which has important clinical implications and may limit usage of CCR5 antagonist family. 28198557 10 9 located observed 1285:1292 arg1 age 1306:1308 an early age 1297:1308 an early age of children which has important clinical implications and may limit usage of CCR5 antagonist family 1297:1408 This evidence showed that X4 viruses can be highly observed at an early age of children which has important clinical implications and may limit usage of CCR5 antagonist family. 28198557 5 10 theme false 653:657 arg1 rate 668:671 a false positive rate 651:671 a false positive rate of 10% 651:678 HIV-1 coreceptor usage was determined using Geno2pheno[coreceptor] with a false positive rate of 10%. 28198557 5 11 theme coreceptor 585:594 arg1 usage 596:600 HIV-1 coreceptor usage 579:600 HIV-1 coreceptor usage 579:600 HIV-1 coreceptor usage was determined using Geno2pheno[coreceptor] with a false positive rate of 10%. 28198557 3 12 theme HIV-1 346:350 arg1 diagnosis 365:373 HIV-1 early infant diagnosis 346:373 HIV-1 early infant diagnosis between 2007 and 2013 346:395 Proviral DNA from 284 HIV-1 infected children who received HIV-1 early infant diagnosis between 2007 and 2013 under the National AIDS Program were studied. 28198557 1 13 theme HIV-1 62:66 arg1 usage 79:83 HIV-1 coreceptor usage 62:83 HIV-1 coreceptor usage in children who were born to HIV-1 infected mothers in Thailand 62:147 HIV-1 coreceptor usage in children who were born to HIV-1 infected mothers in Thailand is not well characterized. 28198557 9 14 link N-linked 1195:1202 arg1 characteristic 1218:1231 N-linked glycosylation characteristic 1195:1231 N-linked glycosylation characteristic 1195:1231 The only significant difference was found in N-linked glycosylation characteristic. 28198557 2 15 from prevalence 186:195 arg1 Thailand 263:270 Thailand 263:270 Thailand 263:270 Here, the prevalence of coreceptor usage and genotype among HIV-1 infected children in Thailand were observed. 28198557 4 16 theme tropism 453:459 arg1 testing 461:467 Genotypic tropism testing 443:467 Genotypic tropism testing 443:467 Genotypic tropism testing was performed based on amplification of the V3 region in a triplicate nested-PCR following by DNA sequencing. 28198557 7 17 theme C. 892:893 arg1 variants 906:913 C. CCR5-using variants 892:913 C. CCR5-using variants 892:913 Two hundred and thirty-seven (89%) children were infected with CRF01_AE, 29 (11%) were subtype B and 1 was subtype C. CCR5-using variants were found in 148 (55%) children and CXCR4-using variants were observed in 119 (45%) children. 28198557 1 18 theme coreceptor 68:77 arg1 usage 79:83 HIV-1 coreceptor usage 62:83 HIV-1 coreceptor usage in children who were born to HIV-1 infected mothers in Thailand 62:147 HIV-1 coreceptor usage in children who were born to HIV-1 infected mothers in Thailand is not well characterized. 28198557 3 19 theme AIDS 416:419 arg1 Program 421:427 the National AIDS Program 403:427 the National AIDS Program 403:427 Proviral DNA from 284 HIV-1 infected children who received HIV-1 early infant diagnosis between 2007 and 2013 under the National AIDS Program were studied. 28198557 9 20 theme N-linked 1195:1202 arg1 characteristic 1218:1231 N-linked glycosylation characteristic 1195:1231 N-linked glycosylation characteristic 1195:1231 The only significant difference was found in N-linked glycosylation characteristic. 28198557 4 21 from nested-PCR 539:548 arg1 amplification 492:504 amplification 492:504 amplification of the V3 region in a triplicate nested-PCR following by DNA sequencing 492:576 Genotypic tropism testing was performed based on amplification of the V3 region in a triplicate nested-PCR following by DNA sequencing. 28198557 0 22 theme coreceptor 6:15 arg1 usage 17:21 HIV-1 coreceptor usage 0:21 HIV-1 coreceptor usage in perinatally infected Thai children. 0:60 HIV-1 coreceptor usage in perinatally infected Thai children. 28198557 9 23 theme glycosylation 1204:1216 arg1 characteristic 1218:1231 N-linked glycosylation characteristic 1195:1231 N-linked glycosylation characteristic 1195:1231 The only significant difference was found in N-linked glycosylation characteristic. 28198557 10 24 theme clinical 1342:1349 arg1 implications 1351:1362 important clinical implications 1332:1362 important clinical implications 1332:1362 This evidence showed that X4 viruses can be highly observed at an early age of children which has important clinical implications and may limit usage of CCR5 antagonist family. 28198557 10 25 theme early 1300:1304 arg1 age 1306:1308 an early age 1297:1308 an early age of children which has important clinical implications and may limit usage of CCR5 antagonist family 1297:1408 This evidence showed that X4 viruses can be highly observed at an early age of children which has important clinical implications and may limit usage of CCR5 antagonist family. 28198557 0 26 theme HIV-1 0:4 arg1 usage 17:21 HIV-1 coreceptor usage 0:21 HIV-1 coreceptor usage in perinatally infected Thai children. 0:60 HIV-1 coreceptor usage in perinatally infected Thai children. 28198557 4 27 theme triplicate 528:537 arg1 nested-PCR 539:548 a triplicate nested-PCR 526:548 a triplicate nested-PCR following by DNA sequencing 526:576 Genotypic tropism testing was performed based on amplification of the V3 region in a triplicate nested-PCR following by DNA sequencing. 28198557 6 28 from children 698:705 arg1 Samples 681:687 Samples 681:687 Samples from 267 children 681:705 Samples from 267 children were successfully amplified and coreceptor usage could be determined. 28198557 3 29 theme National 407:414 arg1 Program 421:427 the National AIDS Program 403:427 the National AIDS Program 403:427 Proviral DNA from 284 HIV-1 infected children who received HIV-1 early infant diagnosis between 2007 and 2013 under the National AIDS Program were studied. 28198557 3 30 theme early 352:356 arg1 diagnosis 365:373 HIV-1 early infant diagnosis 346:373 HIV-1 early infant diagnosis between 2007 and 2013 346:395 Proviral DNA from 284 HIV-1 infected children who received HIV-1 early infant diagnosis between 2007 and 2013 under the National AIDS Program were studied. 28198557 8 31 theme HIV 1083:1085 arg1 infection 1087:1095 HIV infection 1083:1095 HIV infection 1083:1095 No significant differences in coreceptor usage and age, gender, signs of HIV infection, children's or maternal ARV receiving were observed. 28198557 2 32 from genotype 221:228 arg1 Thailand 263:270 Thailand 263:270 Thailand 263:270 Here, the prevalence of coreceptor usage and genotype among HIV-1 infected children in Thailand were observed. 28198557 3 33 theme infant 358:363 arg1 diagnosis 365:373 HIV-1 early infant diagnosis 346:373 HIV-1 early infant diagnosis between 2007 and 2013 346:395 Proviral DNA from 284 HIV-1 infected children who received HIV-1 early infant diagnosis between 2007 and 2013 under the National AIDS Program were studied. 28198557 3 34 from children 324:331 arg1 DNA 296:298 Proviral DNA 287:298 Proviral DNA from 284 HIV-1 infected children who received HIV-1 early infant diagnosis between 2007 and 2013 under the National AIDS Program 287:427 Proviral DNA from 284 HIV-1 infected children who received HIV-1 early infant diagnosis between 2007 and 2013 under the National AIDS Program were studied. 28198557 7 35 located observed 978:985 arg1 % 997:997 45% 995:997 45% 995:997 Two hundred and thirty-seven (89%) children were infected with CRF01_AE, 29 (11%) were subtype B and 1 was subtype C. CCR5-using variants were found in 148 (55%) children and CXCR4-using variants were observed in 119 (45%) children. 28198557 7 35 located observed 978:985 arg2 variants 964:971 CXCR4-using variants 952:971 CXCR4-using variants 952:971 Two hundred and thirty-seven (89%) children were infected with CRF01_AE, 29 (11%) were subtype B and 1 was subtype C. CCR5-using variants were found in 148 (55%) children and CXCR4-using variants were observed in 119 (45%) children. 28198557 7 35 located observed 978:985 arg1 children 1000:1007 119 (45%) children 990:1007 119 (45%) children 990:1007 Two hundred and thirty-seven (89%) children were infected with CRF01_AE, 29 (11%) were subtype B and 1 was subtype C. CCR5-using variants were found in 148 (55%) children and CXCR4-using variants were observed in 119 (45%) children. 28198557 0 36 theme infected 38:45 arg1 children 52:59 perinatally infected Thai children 26:59 perinatally infected Thai children 26:59 HIV-1 coreceptor usage in perinatally infected Thai children. 28198557 9 37 theme significant 1159:1169 arg1 difference 1171:1180 The only significant difference 1150:1180 The only significant difference 1150:1180 The only significant difference was found in N-linked glycosylation characteristic. 28198557 10 38 contain has 1328:1330 arg2 implications 1351:1362 important clinical implications 1332:1362 important clinical implications 1332:1362 This evidence showed that X4 viruses can be highly observed at an early age of children which has important clinical implications and may limit usage of CCR5 antagonist family. 28198557 10 38 contain has 1328:1330 arg1 children 1313:1320 children 1313:1320 children which has important clinical implications and may limit usage of CCR5 antagonist family 1313:1408 This evidence showed that X4 viruses can be highly observed at an early age of children which has important clinical implications and may limit usage of CCR5 antagonist family. 28198557 4 39 from region 516:521 arg1 nested-PCR 539:548 a triplicate nested-PCR 526:548 a triplicate nested-PCR following by DNA sequencing 526:576 Genotypic tropism testing was performed based on amplification of the V3 region in a triplicate nested-PCR following by DNA sequencing. 28198557 4 40 theme V3 513:514 arg1 region 516:521 the V3 region 509:521 the V3 region in a triplicate nested-PCR following by DNA sequencing 509:576 Genotypic tropism testing was performed based on amplification of the V3 region in a triplicate nested-PCR following by DNA sequencing. 28198557 8 41 theme infection 1087:1095 arg1 ARV 1121:1123 maternal ARV 1112:1123 maternal ARV 1112:1123 No significant differences in coreceptor usage and age, gender, signs of HIV infection, children's or maternal ARV receiving were observed. 28198557 8 41 theme infection 1087:1095 arg1 age 1061:1063 age 1061:1063 age 1061:1063 No significant differences in coreceptor usage and age, gender, signs of HIV infection, children's or maternal ARV receiving were observed. 28198557 8 41 theme infection 1087:1095 arg1 gender 1066:1071 gender 1066:1071 gender 1066:1071 No significant differences in coreceptor usage and age, gender, signs of HIV infection, children's or maternal ARV receiving were observed. 28198557 8 41 theme infection 1087:1095 arg1 children 1098:1105 children's 1098:1107 children's 1098:1107 No significant differences in coreceptor usage and age, gender, signs of HIV infection, children's or maternal ARV receiving were observed. 28198557 8 41 theme infection 1087:1095 arg1 usage 1051:1055 coreceptor usage 1040:1055 coreceptor usage 1040:1055 No significant differences in coreceptor usage and age, gender, signs of HIV infection, children's or maternal ARV receiving were observed. 28198557 8 41 theme infection 1087:1095 arg1 signs 1074:1078 signs 1074:1078 signs of HIV infection 1074:1095 No significant differences in coreceptor usage and age, gender, signs of HIV infection, children's or maternal ARV receiving were observed. 28198557 4 42 theme Genotypic 443:451 arg1 testing 461:467 Genotypic tropism testing 443:467 Genotypic tropism testing 443:467 Genotypic tropism testing was performed based on amplification of the V3 region in a triplicate nested-PCR following by DNA sequencing. 28198557 2 43 theme usage 211:215 arg1 genotype 221:228 genotype 221:228 genotype 221:228 Here, the prevalence of coreceptor usage and genotype among HIV-1 infected children in Thailand were observed. 28198557 2 43 theme usage 211:215 arg1 prevalence 186:195 the prevalence 182:195 the prevalence of coreceptor usage 182:215 Here, the prevalence of coreceptor usage and genotype among HIV-1 infected children in Thailand were observed. 28198557 3 44 theme Proviral 287:294 arg1 DNA 296:298 Proviral DNA 287:298 Proviral DNA from 284 HIV-1 infected children who received HIV-1 early infant diagnosis between 2007 and 2013 under the National AIDS Program 287:427 Proviral DNA from 284 HIV-1 infected children who received HIV-1 early infant diagnosis between 2007 and 2013 under the National AIDS Program were studied. 28198557 8 45 from differences 1025:1035 arg1 age 1061:1063 age 1061:1063 age 1061:1063 No significant differences in coreceptor usage and age, gender, signs of HIV infection, children's or maternal ARV receiving were observed. 28198557 8 45 from differences 1025:1035 arg1 usage 1051:1055 coreceptor usage 1040:1055 coreceptor usage 1040:1055 No significant differences in coreceptor usage and age, gender, signs of HIV infection, children's or maternal ARV receiving were observed. 28198557 2 46 theme coreceptor 200:209 arg1 usage 211:215 coreceptor usage 200:215 coreceptor usage 200:215 Here, the prevalence of coreceptor usage and genotype among HIV-1 infected children in Thailand were observed. 28198557 10 47 theme antagonist 1392:1401 arg1 family 1403:1408 CCR5 antagonist family 1387:1408 CCR5 antagonist family 1387:1408 This evidence showed that X4 viruses can be highly observed at an early age of children which has important clinical implications and may limit usage of CCR5 antagonist family. 28198557 0 48 theme Thai 47:50 arg1 children 52:59 perinatally infected Thai children 26:59 perinatally infected Thai children 26:59 HIV-1 coreceptor usage in perinatally infected Thai children. 28198557 10 49 theme family 1403:1408 arg1 usage 1378:1382 usage 1378:1382 usage of CCR5 antagonist family 1378:1408 This evidence showed that X4 viruses can be highly observed at an early age of children which has important clinical implications and may limit usage of CCR5 antagonist family. 28198557 9 50 located found 1186:1190 arg1 characteristic 1218:1231 N-linked glycosylation characteristic 1195:1231 N-linked glycosylation characteristic 1195:1231 The only significant difference was found in N-linked glycosylation characteristic. 28198557 9 50 located found 1186:1190 arg2 difference 1171:1180 The only significant difference 1150:1180 The only significant difference 1150:1180 The only significant difference was found in N-linked glycosylation characteristic. 28198557 6 51 theme coreceptor 739:748 arg1 usage 750:754 coreceptor usage 739:754 coreceptor usage 739:754 Samples from 267 children were successfully amplified and coreceptor usage could be determined. 28198557 10 52 theme children 1313:1320 arg1 age 1306:1308 an early age 1297:1308 an early age of children which has important clinical implications and may limit usage of CCR5 antagonist family 1297:1408 This evidence showed that X4 viruses can be highly observed at an early age of children which has important clinical implications and may limit usage of CCR5 antagonist family. 28198557 7 53 dep subtype 884:890 arg1 observed 978:985 observed 978:985 were observed in 119 (45%) children 973:1007 Two hundred and thirty-seven (89%) children were infected with CRF01_AE, 29 (11%) were subtype B and 1 was subtype C. CCR5-using variants were found in 148 (55%) children and CXCR4-using variants were observed in 119 (45%) children. 28198557 7 53 dep subtype 884:890 arg1 found 920:924 found 920:924 were found in 148 (55%) children 915:946 Two hundred and thirty-seven (89%) children were infected with CRF01_AE, 29 (11%) were subtype B and 1 was subtype C. CCR5-using variants were found in 148 (55%) children and CXCR4-using variants were observed in 119 (45%) children. 28198557 4 54 theme region 516:521 arg1 amplification 492:504 amplification 492:504 amplification of the V3 region in a triplicate nested-PCR following by DNA sequencing 492:576 Genotypic tropism testing was performed based on amplification of the V3 region in a triplicate nested-PCR following by DNA sequencing. 28198557 8 55 theme significant 1013:1023 arg1 differences 1025:1035 No significant differences 1010:1035 No significant differences in coreceptor usage and age, gender, signs of HIV infection, children's or maternal ARV receiving 1010:1133 No significant differences in coreceptor usage and age, gender, signs of HIV infection, children's or maternal ARV receiving were observed. 28198557 2 56 theme infected 242:249 arg1 children 251:258 HIV-1 infected children 236:258 HIV-1 infected children 236:258 Here, the prevalence of coreceptor usage and genotype among HIV-1 infected children in Thailand were observed. 28198557 1 57 theme HIV-1 114:118 arg1 mothers 129:135 HIV-1 infected mothers 114:135 HIV-1 infected mothers 114:135 HIV-1 coreceptor usage in children who were born to HIV-1 infected mothers in Thailand is not well characterized. 28198557 7 58 theme subtype 864:870 arg1 B 872:872 subtype B 864:872 subtype B 864:872 Two hundred and thirty-seven (89%) children were infected with CRF01_AE, 29 (11%) were subtype B and 1 was subtype C. CCR5-using variants were found in 148 (55%) children and CXCR4-using variants were observed in 119 (45%) children. 28198557 5 59 theme % 678:678 arg1 rate 668:671 a false positive rate 651:671 a false positive rate of 10% 651:678 HIV-1 coreceptor usage was determined using Geno2pheno[coreceptor] with a false positive rate of 10%. 28198557 1 60 theme infected 120:127 arg1 mothers 129:135 HIV-1 infected mothers 114:135 HIV-1 infected mothers 114:135 HIV-1 coreceptor usage in children who were born to HIV-1 infected mothers in Thailand is not well characterized. 28198557 10 61 theme important 1332:1340 arg1 implications 1351:1362 important clinical implications 1332:1362 important clinical implications 1332:1362 This evidence showed that X4 viruses can be highly observed at an early age of children which has important clinical implications and may limit usage of CCR5 antagonist family. 28198557 7 62 theme CXCR4-using 952:962 arg1 variants 964:971 CXCR4-using variants 952:971 CXCR4-using variants 952:971 Two hundred and thirty-seven (89%) children were infected with CRF01_AE, 29 (11%) were subtype B and 1 was subtype C. CCR5-using variants were found in 148 (55%) children and CXCR4-using variants were observed in 119 (45%) children. 28198557 10 63 theme X4 1260:1261 arg1 viruses 1263:1269 X4 viruses 1260:1269 X4 viruses 1260:1269 This evidence showed that X4 viruses can be highly observed at an early age of children which has important clinical implications and may limit usage of CCR5 antagonist family. 28198557 7 64 theme CCR5-using 895:904 arg1 variants 906:913 C. CCR5-using variants 892:913 C. CCR5-using variants 892:913 Two hundred and thirty-seven (89%) children were infected with CRF01_AE, 29 (11%) were subtype B and 1 was subtype C. CCR5-using variants were found in 148 (55%) children and CXCR4-using variants were observed in 119 (45%) children. 28198557 3 65 theme infected 315:322 arg1 children 324:331 284 HIV-1 infected children 305:331 284 HIV-1 infected children who received HIV-1 early infant diagnosis between 2007 and 2013 under the National AIDS Program 305:427 Proviral DNA from 284 HIV-1 infected children who received HIV-1 early infant diagnosis between 2007 and 2013 under the National AIDS Program were studied. 28198557 7 66 dep hundred 781:787 arg1 % 809:809 89% 807:809 89% 807:809 Two hundred and thirty-seven (89%) children were infected with CRF01_AE, 29 (11%) were subtype B and 1 was subtype C. CCR5-using variants were found in 148 (55%) children and CXCR4-using variants were observed in 119 (45%) children. 28198557 5 67 dep false 653:657 arg1 positive 659:666 positive 659:666 positive 659:666 HIV-1 coreceptor usage was determined using Geno2pheno[coreceptor] with a false positive rate of 10%. 28148964 5 0 theme N-linked 603:610 arg1 glycans 612:618 mature N-linked glycans 596:618 mature N-linked glycans 596:618 Mitochondrial PrPC was fully processed with mature N-linked glycans and did not require the GPI anchor for localization. 28148964 6 1 theme Protease 673:680 arg1 treatment 682:690 Protease treatment 673:690 Protease treatment of purified mitochondria 673:715 Protease treatment of purified mitochondria suggested that mitochondrial PrPC exists as a transmembrane isoform with the C-terminus facing the mitochondrial matrix and the N-terminus facing the intermembrane space. 28148964 4 2 from mitochondria 463:474 arg1 present 446:452 present 446:452 present 446:452 Here we show that PrPC is present in brain mitochondria from 6-12 week old wild-type and transgenic mice in the absence of disease. 28148964 4 2 from mitochondria 463:474 arg1 absence 532:538 the absence 528:538 the absence of disease 528:549 Here we show that PrPC is present in brain mitochondria from 6-12 week old wild-type and transgenic mice in the absence of disease. 28148964 2 3 theme diseases 318:325 arg1 agent 285:289 the causative agent 271:289 the causative agent of neurodegenerative prion diseases 271:325 PrPC misfolds to a pathogenic isoform PrPSc, the causative agent of neurodegenerative prion diseases. 28148964 2 3 theme diseases 318:325 arg1 PrPSc 264:268 a pathogenic isoform PrPSc 243:268 a pathogenic isoform PrPSc 243:268 PrPC misfolds to a pathogenic isoform PrPSc, the causative agent of neurodegenerative prion diseases. 28148964 7 4 theme mutation 996:1003 arg1 absence 967:973 the absence 963:973 the absence of disease, old age, mutation, or overexpression 963:1022 Taken together, our data suggest that PrPC can be found in mitochondria in the absence of disease, old age, mutation, or overexpression and that PrPC may affect mitochondrial function. 28148964 7 5 theme mitochondrial 1049:1061 arg1 function 1063:1070 mitochondrial function 1049:1070 mitochondrial function 1049:1070 Taken together, our data suggest that PrPC can be found in mitochondria in the absence of disease, old age, mutation, or overexpression and that PrPC may affect mitochondrial function. 28148964 5 6 theme Mitochondrial 552:564 arg1 PrPC 566:569 Mitochondrial PrPC 552:569 Mitochondrial PrPC 552:569 Mitochondrial PrPC was fully processed with mature N-linked glycans and did not require the GPI anchor for localization. 28148964 2 7 theme isoform 256:262 arg1 agent 285:289 the causative agent 271:289 the causative agent of neurodegenerative prion diseases 271:325 PrPC misfolds to a pathogenic isoform PrPSc, the causative agent of neurodegenerative prion diseases. 28148964 2 7 theme isoform 256:262 arg1 PrPSc 264:268 a pathogenic isoform PrPSc 243:268 a pathogenic isoform PrPSc 243:268 PrPC misfolds to a pathogenic isoform PrPSc, the causative agent of neurodegenerative prion diseases. 28148964 4 8 theme disease 543:549 arg1 absence 532:538 the absence 528:538 the absence of disease 528:549 Here we show that PrPC is present in brain mitochondria from 6-12 week old wild-type and transgenic mice in the absence of disease. 28148964 2 9 theme causative 275:283 arg1 agent 285:289 the causative agent 271:289 the causative agent of neurodegenerative prion diseases 271:325 PrPC misfolds to a pathogenic isoform PrPSc, the causative agent of neurodegenerative prion diseases. 28148964 2 9 theme causative 275:283 arg1 PrPSc 264:268 a pathogenic isoform PrPSc 243:268 a pathogenic isoform PrPSc 243:268 PrPC misfolds to a pathogenic isoform PrPSc, the causative agent of neurodegenerative prion diseases. 28148964 2 10 theme pathogenic 245:254 arg1 agent 285:289 the causative agent 271:289 the causative agent of neurodegenerative prion diseases 271:325 PrPC misfolds to a pathogenic isoform PrPSc, the causative agent of neurodegenerative prion diseases. 28148964 2 10 theme pathogenic 245:254 arg1 PrPSc 264:268 a pathogenic isoform PrPSc 243:268 a pathogenic isoform PrPSc 243:268 PrPC misfolds to a pathogenic isoform PrPSc, the causative agent of neurodegenerative prion diseases. 28148964 0 11 from mitochondria 37:48 arg1 present 26:32 present 26:32 present 26:32 Cellular prion protein is present in mitochondria of healthy mice. 28148964 4 12 from present 446:452 arg1 mitochondria 463:474 brain mitochondria 457:474 brain mitochondria from 6-12 week old wild-type and transgenic mice in the absence of disease 457:549 Here we show that PrPC is present in brain mitochondria from 6-12 week old wild-type and transgenic mice in the absence of disease. 28148964 6 13 theme transmembrane 763:775 arg1 isoform 777:783 a transmembrane isoform 761:783 a transmembrane isoform with the C-terminus facing the mitochondrial matrix and the N-terminus facing the intermembrane space 761:885 Protease treatment of purified mitochondria suggested that mitochondrial PrPC exists as a transmembrane isoform with the C-terminus facing the mitochondrial matrix and the N-terminus facing the intermembrane space. 28148964 3 14 theme cellular 397:404 arg1 localization 406:417 its cellular localization 393:417 its cellular localization 393:417 The precise function of PrPC remains elusive but may depend upon its cellular localization. 28148964 0 15 attach present 26:32 arg1 mitochondria 37:48 mitochondria 37:48 mitochondria of healthy mice 37:64 Cellular prion protein is present in mitochondria of healthy mice. 28148964 0 15 attach present 26:32 arg2 protein 15:21 Cellular prion protein 0:21 Cellular prion protein 0:21 Cellular prion protein is present in mitochondria of healthy mice. 28148964 1 16 theme Cellular 67:74 arg1 protein 82:88 Cellular prion protein 67:88 Cellular prion protein (PrPC) 67:95 Cellular prion protein (PrPC) is a mammalian glycoprotein which is usually found anchored to the plasma membrane via a glycophosphatidylinositol (GPI) anchor. 28148964 1 16 theme Cellular 67:74 arg1 glycoprotein 112:123 a mammalian glycoprotein 100:123 a mammalian glycoprotein which is usually found anchored to the plasma membrane via a glycophosphatidylinositol (GPI) anchor 100:223 Cellular prion protein (PrPC) is a mammalian glycoprotein which is usually found anchored to the plasma membrane via a glycophosphatidylinositol (GPI) anchor. 28148964 1 16 theme Cellular 67:74 arg1 PrPC 91:94 PrPC 91:94 PrPC 91:94 Cellular prion protein (PrPC) is a mammalian glycoprotein which is usually found anchored to the plasma membrane via a glycophosphatidylinositol (GPI) anchor. 28148964 0 17 theme prion 9:13 arg1 protein 15:21 Cellular prion protein 0:21 Cellular prion protein 0:21 Cellular prion protein is present in mitochondria of healthy mice. 28148964 0 18 from present 26:32 arg1 mitochondria 37:48 mitochondria 37:48 mitochondria of healthy mice 37:64 Cellular prion protein is present in mitochondria of healthy mice. 28148964 1 19 theme prion 76:80 arg1 protein 82:88 Cellular prion protein 67:88 Cellular prion protein (PrPC) 67:95 Cellular prion protein (PrPC) is a mammalian glycoprotein which is usually found anchored to the plasma membrane via a glycophosphatidylinositol (GPI) anchor. 28148964 1 19 theme prion 76:80 arg1 glycoprotein 112:123 a mammalian glycoprotein 100:123 a mammalian glycoprotein which is usually found anchored to the plasma membrane via a glycophosphatidylinositol (GPI) anchor 100:223 Cellular prion protein (PrPC) is a mammalian glycoprotein which is usually found anchored to the plasma membrane via a glycophosphatidylinositol (GPI) anchor. 28148964 1 19 theme prion 76:80 arg1 PrPC 91:94 PrPC 91:94 PrPC 91:94 Cellular prion protein (PrPC) is a mammalian glycoprotein which is usually found anchored to the plasma membrane via a glycophosphatidylinositol (GPI) anchor. 28148964 6 20 theme intermembrane 867:879 arg1 space 881:885 the intermembrane space 863:885 the intermembrane space 863:885 Protease treatment of purified mitochondria suggested that mitochondrial PrPC exists as a transmembrane isoform with the C-terminus facing the mitochondrial matrix and the N-terminus facing the intermembrane space. 28148964 0 21 theme Cellular 0:7 arg1 protein 15:21 Cellular prion protein 0:21 Cellular prion protein 0:21 Cellular prion protein is present in mitochondria of healthy mice. 28148964 4 22 theme transgenic 509:518 arg1 mice 520:523 6-12 week old wild-type and transgenic mice 481:523 6-12 week old wild-type and transgenic mice 481:523 Here we show that PrPC is present in brain mitochondria from 6-12 week old wild-type and transgenic mice in the absence of disease. 28148964 5 23 theme mature 596:601 arg1 glycans 612:618 mature N-linked glycans 596:618 mature N-linked glycans 596:618 Mitochondrial PrPC was fully processed with mature N-linked glycans and did not require the GPI anchor for localization. 28148964 4 24 from mice 520:523 arg1 mitochondria 463:474 brain mitochondria 457:474 brain mitochondria from 6-12 week old wild-type and transgenic mice in the absence of disease 457:549 Here we show that PrPC is present in brain mitochondria from 6-12 week old wild-type and transgenic mice in the absence of disease. 28148964 7 25 theme overexpression 1009:1022 arg1 absence 967:973 the absence 963:973 the absence of disease, old age, mutation, or overexpression 963:1022 Taken together, our data suggest that PrPC can be found in mitochondria in the absence of disease, old age, mutation, or overexpression and that PrPC may affect mitochondrial function. 28148964 6 26 with isoform 777:783 arg1 C-terminus 794:803 the C-terminus 790:803 the C-terminus facing the mitochondrial matrix and the N-terminus facing the intermembrane space 790:885 Protease treatment of purified mitochondria suggested that mitochondrial PrPC exists as a transmembrane isoform with the C-terminus facing the mitochondrial matrix and the N-terminus facing the intermembrane space. 28148964 1 27 theme plasma 164:169 arg1 membrane 171:178 the plasma membrane 160:178 the plasma membrane 160:178 Cellular prion protein (PrPC) is a mammalian glycoprotein which is usually found anchored to the plasma membrane via a glycophosphatidylinositol (GPI) anchor. 28148964 4 28 attach present 446:452 arg1 mitochondria 463:474 brain mitochondria 457:474 brain mitochondria from 6-12 week old wild-type and transgenic mice in the absence of disease 457:549 Here we show that PrPC is present in brain mitochondria from 6-12 week old wild-type and transgenic mice in the absence of disease. 28148964 4 28 attach present 446:452 arg2 PrPC 438:441 PrPC 438:441 PrPC 438:441 Here we show that PrPC is present in brain mitochondria from 6-12 week old wild-type and transgenic mice in the absence of disease. 28148964 7 29 located found 938:942 arg2 PrPC 926:929 PrPC 926:929 PrPC 926:929 Taken together, our data suggest that PrPC can be found in mitochondria in the absence of disease, old age, mutation, or overexpression and that PrPC may affect mitochondrial function. 28148964 7 29 located found 938:942 arg1 absence 967:973 the absence 963:973 the absence of disease, old age, mutation, or overexpression 963:1022 Taken together, our data suggest that PrPC can be found in mitochondria in the absence of disease, old age, mutation, or overexpression and that PrPC may affect mitochondrial function. 28148964 7 29 located found 938:942 arg1 mitochondria 947:958 mitochondria 947:958 mitochondria 947:958 Taken together, our data suggest that PrPC can be found in mitochondria in the absence of disease, old age, mutation, or overexpression and that PrPC may affect mitochondrial function. 28148964 5 30 link N-linked 603:610 arg1 glycans 612:618 mature N-linked glycans 596:618 mature N-linked glycans 596:618 Mitochondrial PrPC was fully processed with mature N-linked glycans and did not require the GPI anchor for localization. 28148964 4 31 located present 446:452 arg1 mitochondria 463:474 brain mitochondria 457:474 brain mitochondria from 6-12 week old wild-type and transgenic mice in the absence of disease 457:549 Here we show that PrPC is present in brain mitochondria from 6-12 week old wild-type and transgenic mice in the absence of disease. 28148964 4 31 located present 446:452 arg2 PrPC 438:441 PrPC 438:441 PrPC 438:441 Here we show that PrPC is present in brain mitochondria from 6-12 week old wild-type and transgenic mice in the absence of disease. 28148964 7 32 theme age 991:993 arg1 absence 967:973 the absence 963:973 the absence of disease, old age, mutation, or overexpression 963:1022 Taken together, our data suggest that PrPC can be found in mitochondria in the absence of disease, old age, mutation, or overexpression and that PrPC may affect mitochondrial function. 28148964 6 33 theme mitochondrial 732:744 arg1 PrPC 746:749 mitochondrial PrPC 732:749 mitochondrial PrPC 732:749 Protease treatment of purified mitochondria suggested that mitochondrial PrPC exists as a transmembrane isoform with the C-terminus facing the mitochondrial matrix and the N-terminus facing the intermembrane space. 28148964 1 34 dep found 142:146 arg1 anchored 148:155 anchored 148:155 is usually found anchored to the plasma membrane via a glycophosphatidylinositol (GPI) anchor 131:223 Cellular prion protein (PrPC) is a mammalian glycoprotein which is usually found anchored to the plasma membrane via a glycophosphatidylinositol (GPI) anchor. 28148964 2 35 theme prion 312:316 arg1 diseases 318:325 neurodegenerative prion diseases 294:325 neurodegenerative prion diseases 294:325 PrPC misfolds to a pathogenic isoform PrPSc, the causative agent of neurodegenerative prion diseases. 28148964 4 36 theme wild-type 495:503 arg1 mice 520:523 6-12 week old wild-type and transgenic mice 481:523 6-12 week old wild-type and transgenic mice 481:523 Here we show that PrPC is present in brain mitochondria from 6-12 week old wild-type and transgenic mice in the absence of disease. 28148964 1 37 gly glycoprotein 112:123 arg1 protein 82:88 Cellular prion protein 67:88 Cellular prion protein (PrPC) 67:95 Cellular prion protein (PrPC) is a mammalian glycoprotein which is usually found anchored to the plasma membrane via a glycophosphatidylinositol (GPI) anchor. 28148964 1 37 gly glycoprotein 112:123 arg1 glycoprotein 112:123 a mammalian glycoprotein 100:123 a mammalian glycoprotein which is usually found anchored to the plasma membrane via a glycophosphatidylinositol (GPI) anchor 100:223 Cellular prion protein (PrPC) is a mammalian glycoprotein which is usually found anchored to the plasma membrane via a glycophosphatidylinositol (GPI) anchor. 28148964 6 38 theme mitochondrial 816:828 arg1 matrix 830:835 the mitochondrial matrix 812:835 the mitochondrial matrix 812:835 Protease treatment of purified mitochondria suggested that mitochondrial PrPC exists as a transmembrane isoform with the C-terminus facing the mitochondrial matrix and the N-terminus facing the intermembrane space. 28148964 2 39 theme neurodegenerative 294:310 arg1 diseases 318:325 neurodegenerative prion diseases 294:325 neurodegenerative prion diseases 294:325 PrPC misfolds to a pathogenic isoform PrPSc, the causative agent of neurodegenerative prion diseases. 28148964 4 40 theme old 491:493 arg1 mice 520:523 6-12 week old wild-type and transgenic mice 481:523 6-12 week old wild-type and transgenic mice 481:523 Here we show that PrPC is present in brain mitochondria from 6-12 week old wild-type and transgenic mice in the absence of disease. 28148964 7 41 theme old 987:989 arg1 age 991:993 old age 987:993 old age 987:993 Taken together, our data suggest that PrPC can be found in mitochondria in the absence of disease, old age, mutation, or overexpression and that PrPC may affect mitochondrial function. 28148964 0 42 located present 26:32 arg1 mitochondria 37:48 mitochondria 37:48 mitochondria of healthy mice 37:64 Cellular prion protein is present in mitochondria of healthy mice. 28148964 0 42 located present 26:32 arg2 protein 15:21 Cellular prion protein 0:21 Cellular prion protein 0:21 Cellular prion protein is present in mitochondria of healthy mice. 28148964 6 43 theme mitochondria 704:715 arg1 treatment 682:690 Protease treatment 673:690 Protease treatment of purified mitochondria 673:715 Protease treatment of purified mitochondria suggested that mitochondrial PrPC exists as a transmembrane isoform with the C-terminus facing the mitochondrial matrix and the N-terminus facing the intermembrane space. 28148964 1 44 theme glycophosphatidylinositol 186:210 arg1 anchor 218:223 a glycophosphatidylinositol (GPI) anchor 184:223 a glycophosphatidylinositol (GPI) anchor 184:223 Cellular prion protein (PrPC) is a mammalian glycoprotein which is usually found anchored to the plasma membrane via a glycophosphatidylinositol (GPI) anchor. 28148964 5 45 theme GPI 644:646 arg1 anchor 648:653 the GPI anchor 640:653 the GPI anchor for localization 640:670 Mitochondrial PrPC was fully processed with mature N-linked glycans and did not require the GPI anchor for localization. 28148964 7 46 theme disease 978:984 arg1 absence 967:973 the absence 963:973 the absence of disease, old age, mutation, or overexpression 963:1022 Taken together, our data suggest that PrPC can be found in mitochondria in the absence of disease, old age, mutation, or overexpression and that PrPC may affect mitochondrial function. 28148964 6 47 theme purified 695:702 arg1 mitochondria 704:715 purified mitochondria 695:715 purified mitochondria 695:715 Protease treatment of purified mitochondria suggested that mitochondrial PrPC exists as a transmembrane isoform with the C-terminus facing the mitochondrial matrix and the N-terminus facing the intermembrane space. 28148964 1 48 theme mammalian 102:110 arg1 protein 82:88 Cellular prion protein 67:88 Cellular prion protein (PrPC) 67:95 Cellular prion protein (PrPC) is a mammalian glycoprotein which is usually found anchored to the plasma membrane via a glycophosphatidylinositol (GPI) anchor. 28148964 1 48 theme mammalian 102:110 arg1 glycoprotein 112:123 a mammalian glycoprotein 100:123 a mammalian glycoprotein which is usually found anchored to the plasma membrane via a glycophosphatidylinositol (GPI) anchor 100:223 Cellular prion protein (PrPC) is a mammalian glycoprotein which is usually found anchored to the plasma membrane via a glycophosphatidylinositol (GPI) anchor. 28148964 0 49 theme mice 61:64 arg1 mitochondria 37:48 mitochondria 37:48 mitochondria of healthy mice 37:64 Cellular prion protein is present in mitochondria of healthy mice. 28148964 1 50 theme GPI 213:215 arg1 anchor 218:223 a glycophosphatidylinositol (GPI) anchor 184:223 a glycophosphatidylinositol (GPI) anchor 184:223 Cellular prion protein (PrPC) is a mammalian glycoprotein which is usually found anchored to the plasma membrane via a glycophosphatidylinositol (GPI) anchor. 28148964 0 51 theme healthy 53:59 arg1 mice 61:64 healthy mice 53:64 healthy mice 53:64 Cellular prion protein is present in mitochondria of healthy mice. 28148964 4 52 theme brain 457:461 arg1 mitochondria 463:474 brain mitochondria 457:474 brain mitochondria from 6-12 week old wild-type and transgenic mice in the absence of disease 457:549 Here we show that PrPC is present in brain mitochondria from 6-12 week old wild-type and transgenic mice in the absence of disease. 28148964 3 53 theme PrPC 352:355 arg1 function 340:347 The precise function 328:347 The precise function of PrPC 328:355 The precise function of PrPC remains elusive but may depend upon its cellular localization. 28148964 3 54 theme precise 332:338 arg1 function 340:347 The precise function 328:347 The precise function of PrPC 328:355 The precise function of PrPC remains elusive but may depend upon its cellular localization. 28103685 4 0 theme homogeneous 1042:1052 arg1 glycoforms 1054:1063 homogeneous glycoforms 1042:1063 homogeneous glycoforms with well-defined glycan structures and optimal effector functions 1042:1130 Using BfFucH coupled with endoglycosidases and the emerging glycosynthases allows glycoengineering of IgG antibodies to provide homogeneous glycoforms with well-defined glycan structures and optimal effector functions. 28103685 2 1 theme linkages 578:585 arg1 cleavage 442:449 the cleavage 438:449 the cleavage of the fucosidic bond in glycans and glycoconjugates, particularly the Fuc-α-1,2-Gal, Fuc-α-1,3/4-GlcNAc, and Fuc-α-1,6-GlcNAc linkages 438:585 The enzyme α-l-fucosidase is involved in the cleavage of the fucosidic bond in glycans and glycoconjugates, particularly the Fuc-α-1,2-Gal, Fuc-α-1,3/4-GlcNAc, and Fuc-α-1,6-GlcNAc linkages. 28103685 3 2 theme glycosidases 695:706 arg1 library 674:680 a library 672:680 a library of bacterial glycosidases expressed in E. coli 672:727 Here, we report a highly efficient fucosidase, designated as BfFucH identified from a library of bacterial glycosidases expressed in E. coli from the CAZy database, which is capable of hydrolyzing the aforementioned fucosidic linkages, especially the α-1,6-linkage from the N-linked Fuc-α-1,6-GlcNAc residue on glycoproteins. 28103685 2 3 from linkages 578:585 arg1 glycoconjugates 488:502 glycoconjugates 488:502 glycoconjugates 488:502 The enzyme α-l-fucosidase is involved in the cleavage of the fucosidic bond in glycans and glycoconjugates, particularly the Fuc-α-1,2-Gal, Fuc-α-1,3/4-GlcNAc, and Fuc-α-1,6-GlcNAc linkages. 28103685 2 3 from linkages 578:585 arg1 glycans 476:482 glycans 476:482 glycans 476:482 The enzyme α-l-fucosidase is involved in the cleavage of the fucosidic bond in glycans and glycoconjugates, particularly the Fuc-α-1,2-Gal, Fuc-α-1,3/4-GlcNAc, and Fuc-α-1,6-GlcNAc linkages. 28103685 1 4 theme rheumatoid 349:358 arg1 arthritis 360:368 rheumatoid arthritis 349:368 rheumatoid arthritis 349:368 Fucose is an important component of many oligo- and polysaccharide structures as well as glycoproteins and glycolipids, which are often associated with a variety of physiological processes ranging from fertilization, embryogenesis, signal transduction, and disease progression, such as rheumatoid arthritis, inflammation, and cancer. 28103685 3 5 from residue 888:894 arg1 glycoproteins 899:911 glycoproteins 899:911 glycoproteins 899:911 Here, we report a highly efficient fucosidase, designated as BfFucH identified from a library of bacterial glycosidases expressed in E. coli from the CAZy database, which is capable of hydrolyzing the aforementioned fucosidic linkages, especially the α-1,6-linkage from the N-linked Fuc-α-1,6-GlcNAc residue on glycoproteins. 28103685 2 6 theme Fuc-α-1,2-Gal 522:534 arg1 bond 468:471 the fucosidic bond 454:471 the fucosidic bond in glycans and glycoconjugates 454:502 The enzyme α-l-fucosidase is involved in the cleavage of the fucosidic bond in glycans and glycoconjugates, particularly the Fuc-α-1,2-Gal, Fuc-α-1,3/4-GlcNAc, and Fuc-α-1,6-GlcNAc linkages. 28103685 3 7 gly glycoproteins 899:911 arg1 glycoproteins 899:911 glycoproteins 899:911 glycoproteins 899:911 Here, we report a highly efficient fucosidase, designated as BfFucH identified from a library of bacterial glycosidases expressed in E. coli from the CAZy database, which is capable of hydrolyzing the aforementioned fucosidic linkages, especially the α-1,6-linkage from the N-linked Fuc-α-1,6-GlcNAc residue on glycoproteins. 28103685 4 8 theme IgG 1016:1018 arg1 antibodies 1020:1029 IgG antibodies 1016:1029 IgG antibodies 1016:1029 Using BfFucH coupled with endoglycosidases and the emerging glycosynthases allows glycoengineering of IgG antibodies to provide homogeneous glycoforms with well-defined glycan structures and optimal effector functions. 28103685 3 9 theme CAZy 738:741 arg1 database 743:750 the CAZy database 734:750 the CAZy database 734:750 Here, we report a highly efficient fucosidase, designated as BfFucH identified from a library of bacterial glycosidases expressed in E. coli from the CAZy database, which is capable of hydrolyzing the aforementioned fucosidic linkages, especially the α-1,6-linkage from the N-linked Fuc-α-1,6-GlcNAc residue on glycoproteins. 28103685 4 10 theme well-defined 1070:1081 arg1 structures 1090:1099 well-defined glycan structures 1070:1099 well-defined glycan structures 1070:1099 Using BfFucH coupled with endoglycosidases and the emerging glycosynthases allows glycoengineering of IgG antibodies to provide homogeneous glycoforms with well-defined glycan structures and optimal effector functions. 28103685 1 11 theme important 76:84 arg1 Fucose 63:68 Fucose 63:68 Fucose 63:68 Fucose is an important component of many oligo- and polysaccharide structures as well as glycoproteins and glycolipids, which are often associated with a variety of physiological processes ranging from fertilization, embryogenesis, signal transduction, and disease progression, such as rheumatoid arthritis, inflammation, and cancer. 28103685 1 11 theme important 76:84 arg1 component 86:94 an important component 73:94 an important component of many oligo- and polysaccharide structures as well as glycoproteins and glycolipids, which are often associated with a variety of physiological processes ranging from fertilization, embryogenesis, signal transduction, and disease progression, such as rheumatoid arthritis, inflammation, and cancer 73:394 Fucose is an important component of many oligo- and polysaccharide structures as well as glycoproteins and glycolipids, which are often associated with a variety of physiological processes ranging from fertilization, embryogenesis, signal transduction, and disease progression, such as rheumatoid arthritis, inflammation, and cancer. 28103685 4 12 theme antibodies 1020:1029 arg1 glycoengineering 996:1011 glycoengineering 996:1011 glycoengineering of IgG antibodies 996:1029 Using BfFucH coupled with endoglycosidases and the emerging glycosynthases allows glycoengineering of IgG antibodies to provide homogeneous glycoforms with well-defined glycan structures and optimal effector functions. 28103685 0 13 theme Effective 3:11 arg1 Fucosidase 23:32 An Effective Bacterial Fucosidase 0:32 An Effective Bacterial Fucosidase for Glycoprotein Remodeling 0:60 An Effective Bacterial Fucosidase for Glycoprotein Remodeling. 28103685 2 14 from bond 468:471 arg1 glycoconjugates 488:502 glycoconjugates 488:502 glycoconjugates 488:502 The enzyme α-l-fucosidase is involved in the cleavage of the fucosidic bond in glycans and glycoconjugates, particularly the Fuc-α-1,2-Gal, Fuc-α-1,3/4-GlcNAc, and Fuc-α-1,6-GlcNAc linkages. 28103685 2 14 from bond 468:471 arg1 glycans 476:482 glycans 476:482 glycans 476:482 The enzyme α-l-fucosidase is involved in the cleavage of the fucosidic bond in glycans and glycoconjugates, particularly the Fuc-α-1,2-Gal, Fuc-α-1,3/4-GlcNAc, and Fuc-α-1,6-GlcNAc linkages. 28103685 4 15 theme effector 1113:1120 arg1 functions 1122:1130 optimal effector functions 1105:1130 optimal effector functions 1105:1130 Using BfFucH coupled with endoglycosidases and the emerging glycosynthases allows glycoengineering of IgG antibodies to provide homogeneous glycoforms with well-defined glycan structures and optimal effector functions. 28103685 2 16 theme Fuc-α-1,6-GlcNAc 561:576 arg1 linkages 578:585 Fuc-α-1,6-GlcNAc linkages 561:585 Fuc-α-1,6-GlcNAc linkages 561:585 The enzyme α-l-fucosidase is involved in the cleavage of the fucosidic bond in glycans and glycoconjugates, particularly the Fuc-α-1,2-Gal, Fuc-α-1,3/4-GlcNAc, and Fuc-α-1,6-GlcNAc linkages. 28103685 4 17 with glycoforms 1054:1063 arg1 functions 1122:1130 optimal effector functions 1105:1130 optimal effector functions 1105:1130 Using BfFucH coupled with endoglycosidases and the emerging glycosynthases allows glycoengineering of IgG antibodies to provide homogeneous glycoforms with well-defined glycan structures and optimal effector functions. 28103685 4 17 with glycoforms 1054:1063 arg1 structures 1090:1099 well-defined glycan structures 1070:1099 well-defined glycan structures 1070:1099 Using BfFucH coupled with endoglycosidases and the emerging glycosynthases allows glycoengineering of IgG antibodies to provide homogeneous glycoforms with well-defined glycan structures and optimal effector functions. 28103685 1 18 theme many 99:102 arg1 oligo- 104:109 many oligo- and polysaccharide structures 99:139 oligo- 104:109 Fucose is an important component of many oligo- and polysaccharide structures as well as glycoproteins and glycolipids, which are often associated with a variety of physiological processes ranging from fertilization, embryogenesis, signal transduction, and disease progression, such as rheumatoid arthritis, inflammation, and cancer. 28103685 0 19 theme Bacterial 13:21 arg1 Fucosidase 23:32 An Effective Bacterial Fucosidase 0:32 An Effective Bacterial Fucosidase for Glycoprotein Remodeling 0:60 An Effective Bacterial Fucosidase for Glycoprotein Remodeling. 28103685 1 20 theme signal 295:300 arg1 transduction 302:313 signal transduction 295:313 signal transduction 295:313 Fucose is an important component of many oligo- and polysaccharide structures as well as glycoproteins and glycolipids, which are often associated with a variety of physiological processes ranging from fertilization, embryogenesis, signal transduction, and disease progression, such as rheumatoid arthritis, inflammation, and cancer. 28103685 4 21 theme emerging 965:972 arg1 glycosynthases 974:987 the emerging glycosynthases 961:987 the emerging glycosynthases 961:987 Using BfFucH coupled with endoglycosidases and the emerging glycosynthases allows glycoengineering of IgG antibodies to provide homogeneous glycoforms with well-defined glycan structures and optimal effector functions. 28103685 1 22 theme oligo- 104:109 arg1 glycolipids 170:180 glycolipids 170:180 glycolipids 170:180 Fucose is an important component of many oligo- and polysaccharide structures as well as glycoproteins and glycolipids, which are often associated with a variety of physiological processes ranging from fertilization, embryogenesis, signal transduction, and disease progression, such as rheumatoid arthritis, inflammation, and cancer. 28103685 1 22 theme oligo- 104:109 arg1 glycoproteins 152:164 glycoproteins 152:164 glycoproteins 152:164 Fucose is an important component of many oligo- and polysaccharide structures as well as glycoproteins and glycolipids, which are often associated with a variety of physiological processes ranging from fertilization, embryogenesis, signal transduction, and disease progression, such as rheumatoid arthritis, inflammation, and cancer. 28103685 1 22 theme oligo- 104:109 arg1 Fucose 63:68 Fucose 63:68 Fucose 63:68 Fucose is an important component of many oligo- and polysaccharide structures as well as glycoproteins and glycolipids, which are often associated with a variety of physiological processes ranging from fertilization, embryogenesis, signal transduction, and disease progression, such as rheumatoid arthritis, inflammation, and cancer. 28103685 1 22 theme oligo- 104:109 arg1 component 86:94 an important component 73:94 an important component of many oligo- and polysaccharide structures as well as glycoproteins and glycolipids, which are often associated with a variety of physiological processes ranging from fertilization, embryogenesis, signal transduction, and disease progression, such as rheumatoid arthritis, inflammation, and cancer 73:394 Fucose is an important component of many oligo- and polysaccharide structures as well as glycoproteins and glycolipids, which are often associated with a variety of physiological processes ranging from fertilization, embryogenesis, signal transduction, and disease progression, such as rheumatoid arthritis, inflammation, and cancer. 28103685 0 23 theme Glycoprotein 38:49 arg1 Remodeling 51:60 Glycoprotein Remodeling 38:60 Glycoprotein Remodeling 38:60 An Effective Bacterial Fucosidase for Glycoprotein Remodeling. 28103685 2 24 from glycans 476:482 arg1 cleavage 442:449 the cleavage 438:449 the cleavage of the fucosidic bond in glycans and glycoconjugates, particularly the Fuc-α-1,2-Gal, Fuc-α-1,3/4-GlcNAc, and Fuc-α-1,6-GlcNAc linkages 438:585 The enzyme α-l-fucosidase is involved in the cleavage of the fucosidic bond in glycans and glycoconjugates, particularly the Fuc-α-1,2-Gal, Fuc-α-1,3/4-GlcNAc, and Fuc-α-1,6-GlcNAc linkages. 28103685 2 25 theme bond 468:471 arg1 cleavage 442:449 the cleavage 438:449 the cleavage of the fucosidic bond in glycans and glycoconjugates, particularly the Fuc-α-1,2-Gal, Fuc-α-1,3/4-GlcNAc, and Fuc-α-1,6-GlcNAc linkages 438:585 The enzyme α-l-fucosidase is involved in the cleavage of the fucosidic bond in glycans and glycoconjugates, particularly the Fuc-α-1,2-Gal, Fuc-α-1,3/4-GlcNAc, and Fuc-α-1,6-GlcNAc linkages. 28103685 2 26 theme Fuc-α-1,3/4-GlcNAc 537:554 arg1 cleavage 442:449 the cleavage 438:449 the cleavage of the fucosidic bond in glycans and glycoconjugates, particularly the Fuc-α-1,2-Gal, Fuc-α-1,3/4-GlcNAc, and Fuc-α-1,6-GlcNAc linkages 438:585 The enzyme α-l-fucosidase is involved in the cleavage of the fucosidic bond in glycans and glycoconjugates, particularly the Fuc-α-1,2-Gal, Fuc-α-1,3/4-GlcNAc, and Fuc-α-1,6-GlcNAc linkages. 28103685 3 27 theme aforementioned 789:802 arg1 linkages 814:821 the aforementioned fucosidic linkages 785:821 the aforementioned fucosidic linkages 785:821 Here, we report a highly efficient fucosidase, designated as BfFucH identified from a library of bacterial glycosidases expressed in E. coli from the CAZy database, which is capable of hydrolyzing the aforementioned fucosidic linkages, especially the α-1,6-linkage from the N-linked Fuc-α-1,6-GlcNAc residue on glycoproteins. 28103685 3 27 theme aforementioned 789:802 arg1 α-1,6-linkage 839:851 the α-1,6-linkage 835:851 especially the α-1,6-linkage 824:851 Here, we report a highly efficient fucosidase, designated as BfFucH identified from a library of bacterial glycosidases expressed in E. coli from the CAZy database, which is capable of hydrolyzing the aforementioned fucosidic linkages, especially the α-1,6-linkage from the N-linked Fuc-α-1,6-GlcNAc residue on glycoproteins. 28103685 2 28 theme enzyme 401:406 arg1 α-l-fucosidase 408:421 The enzyme α-l-fucosidase 397:421 The enzyme α-l-fucosidase 397:421 The enzyme α-l-fucosidase is involved in the cleavage of the fucosidic bond in glycans and glycoconjugates, particularly the Fuc-α-1,2-Gal, Fuc-α-1,3/4-GlcNAc, and Fuc-α-1,6-GlcNAc linkages. 28103685 2 29 theme fucosidic 458:466 arg1 bond 468:471 the fucosidic bond 454:471 the fucosidic bond in glycans and glycoconjugates 454:502 The enzyme α-l-fucosidase is involved in the cleavage of the fucosidic bond in glycans and glycoconjugates, particularly the Fuc-α-1,2-Gal, Fuc-α-1,3/4-GlcNAc, and Fuc-α-1,6-GlcNAc linkages. 28103685 4 30 theme optimal 1105:1111 arg1 functions 1122:1130 optimal effector functions 1105:1130 optimal effector functions 1105:1130 Using BfFucH coupled with endoglycosidases and the emerging glycosynthases allows glycoengineering of IgG antibodies to provide homogeneous glycoforms with well-defined glycan structures and optimal effector functions. 28103685 2 31 from glycoconjugates 488:502 arg1 cleavage 442:449 the cleavage 438:449 the cleavage of the fucosidic bond in glycans and glycoconjugates, particularly the Fuc-α-1,2-Gal, Fuc-α-1,3/4-GlcNAc, and Fuc-α-1,6-GlcNAc linkages 438:585 The enzyme α-l-fucosidase is involved in the cleavage of the fucosidic bond in glycans and glycoconjugates, particularly the Fuc-α-1,2-Gal, Fuc-α-1,3/4-GlcNAc, and Fuc-α-1,6-GlcNAc linkages. 28103685 2 32 from cleavage 442:449 arg1 glycoconjugates 488:502 glycoconjugates 488:502 glycoconjugates 488:502 The enzyme α-l-fucosidase is involved in the cleavage of the fucosidic bond in glycans and glycoconjugates, particularly the Fuc-α-1,2-Gal, Fuc-α-1,3/4-GlcNAc, and Fuc-α-1,6-GlcNAc linkages. 28103685 2 32 from cleavage 442:449 arg1 glycans 476:482 glycans 476:482 glycans 476:482 The enzyme α-l-fucosidase is involved in the cleavage of the fucosidic bond in glycans and glycoconjugates, particularly the Fuc-α-1,2-Gal, Fuc-α-1,3/4-GlcNAc, and Fuc-α-1,6-GlcNAc linkages. 28103685 1 33 theme disease 320:326 arg1 progression 328:338 disease progression 320:338 disease progression 320:338 Fucose is an important component of many oligo- and polysaccharide structures as well as glycoproteins and glycolipids, which are often associated with a variety of physiological processes ranging from fertilization, embryogenesis, signal transduction, and disease progression, such as rheumatoid arthritis, inflammation, and cancer. 28103685 3 34 theme bacterial 685:693 arg1 glycosidases 695:706 bacterial glycosidases 685:706 bacterial glycosidases 685:706 Here, we report a highly efficient fucosidase, designated as BfFucH identified from a library of bacterial glycosidases expressed in E. coli from the CAZy database, which is capable of hydrolyzing the aforementioned fucosidic linkages, especially the α-1,6-linkage from the N-linked Fuc-α-1,6-GlcNAc residue on glycoproteins. 28103685 1 35 theme polysaccharide 115:128 arg1 structures 130:139 many oligo- and polysaccharide structures 99:139 structures 130:139 Fucose is an important component of many oligo- and polysaccharide structures as well as glycoproteins and glycolipids, which are often associated with a variety of physiological processes ranging from fertilization, embryogenesis, signal transduction, and disease progression, such as rheumatoid arthritis, inflammation, and cancer. 28103685 3 36 theme Fuc-α-1,6-GlcNAc 871:886 arg1 residue 888:894 the N-linked Fuc-α-1,6-GlcNAc residue 858:894 the N-linked Fuc-α-1,6-GlcNAc residue on glycoproteins 858:911 Here, we report a highly efficient fucosidase, designated as BfFucH identified from a library of bacterial glycosidases expressed in E. coli from the CAZy database, which is capable of hydrolyzing the aforementioned fucosidic linkages, especially the α-1,6-linkage from the N-linked Fuc-α-1,6-GlcNAc residue on glycoproteins. 28103685 3 37 link N-linked 862:869 arg1 residue 888:894 the N-linked Fuc-α-1,6-GlcNAc residue 858:894 the N-linked Fuc-α-1,6-GlcNAc residue on glycoproteins 858:911 Here, we report a highly efficient fucosidase, designated as BfFucH identified from a library of bacterial glycosidases expressed in E. coli from the CAZy database, which is capable of hydrolyzing the aforementioned fucosidic linkages, especially the α-1,6-linkage from the N-linked Fuc-α-1,6-GlcNAc residue on glycoproteins. 28103685 1 38 theme structures 130:139 arg1 glycolipids 170:180 glycolipids 170:180 glycolipids 170:180 Fucose is an important component of many oligo- and polysaccharide structures as well as glycoproteins and glycolipids, which are often associated with a variety of physiological processes ranging from fertilization, embryogenesis, signal transduction, and disease progression, such as rheumatoid arthritis, inflammation, and cancer. 28103685 1 38 theme structures 130:139 arg1 glycoproteins 152:164 glycoproteins 152:164 glycoproteins 152:164 Fucose is an important component of many oligo- and polysaccharide structures as well as glycoproteins and glycolipids, which are often associated with a variety of physiological processes ranging from fertilization, embryogenesis, signal transduction, and disease progression, such as rheumatoid arthritis, inflammation, and cancer. 28103685 1 38 theme structures 130:139 arg1 Fucose 63:68 Fucose 63:68 Fucose 63:68 Fucose is an important component of many oligo- and polysaccharide structures as well as glycoproteins and glycolipids, which are often associated with a variety of physiological processes ranging from fertilization, embryogenesis, signal transduction, and disease progression, such as rheumatoid arthritis, inflammation, and cancer. 28103685 1 38 theme structures 130:139 arg1 component 86:94 an important component 73:94 an important component of many oligo- and polysaccharide structures as well as glycoproteins and glycolipids, which are often associated with a variety of physiological processes ranging from fertilization, embryogenesis, signal transduction, and disease progression, such as rheumatoid arthritis, inflammation, and cancer 73:394 Fucose is an important component of many oligo- and polysaccharide structures as well as glycoproteins and glycolipids, which are often associated with a variety of physiological processes ranging from fertilization, embryogenesis, signal transduction, and disease progression, such as rheumatoid arthritis, inflammation, and cancer. 28103685 1 39 gly glycoproteins 152:164 arg1 glycoproteins 152:164 glycoproteins 152:164 glycoproteins 152:164 Fucose is an important component of many oligo- and polysaccharide structures as well as glycoproteins and glycolipids, which are often associated with a variety of physiological processes ranging from fertilization, embryogenesis, signal transduction, and disease progression, such as rheumatoid arthritis, inflammation, and cancer. 28103685 2 40 from Fuc-α-1,3/4-GlcNAc 537:554 arg1 glycoconjugates 488:502 glycoconjugates 488:502 glycoconjugates 488:502 The enzyme α-l-fucosidase is involved in the cleavage of the fucosidic bond in glycans and glycoconjugates, particularly the Fuc-α-1,2-Gal, Fuc-α-1,3/4-GlcNAc, and Fuc-α-1,6-GlcNAc linkages. 28103685 2 40 from Fuc-α-1,3/4-GlcNAc 537:554 arg1 glycans 476:482 glycans 476:482 glycans 476:482 The enzyme α-l-fucosidase is involved in the cleavage of the fucosidic bond in glycans and glycoconjugates, particularly the Fuc-α-1,2-Gal, Fuc-α-1,3/4-GlcNAc, and Fuc-α-1,6-GlcNAc linkages. 28103685 3 41 theme efficient 613:621 arg1 fucosidase 623:632 a highly efficient fucosidase 604:632 a highly efficient fucosidase 604:632 Here, we report a highly efficient fucosidase, designated as BfFucH identified from a library of bacterial glycosidases expressed in E. coli from the CAZy database, which is capable of hydrolyzing the aforementioned fucosidic linkages, especially the α-1,6-linkage from the N-linked Fuc-α-1,6-GlcNAc residue on glycoproteins. 28103685 3 41 theme efficient 613:621 arg1 capable 762:768 capable 762:768 capable 762:768 Here, we report a highly efficient fucosidase, designated as BfFucH identified from a library of bacterial glycosidases expressed in E. coli from the CAZy database, which is capable of hydrolyzing the aforementioned fucosidic linkages, especially the α-1,6-linkage from the N-linked Fuc-α-1,6-GlcNAc residue on glycoproteins. 28103685 3 42 theme N-linked 862:869 arg1 residue 888:894 the N-linked Fuc-α-1,6-GlcNAc residue 858:894 the N-linked Fuc-α-1,6-GlcNAc residue on glycoproteins 858:911 Here, we report a highly efficient fucosidase, designated as BfFucH identified from a library of bacterial glycosidases expressed in E. coli from the CAZy database, which is capable of hydrolyzing the aforementioned fucosidic linkages, especially the α-1,6-linkage from the N-linked Fuc-α-1,6-GlcNAc residue on glycoproteins. 28103685 1 43 theme physiological 228:240 arg1 processes 242:250 physiological processes 228:250 physiological processes 228:250 Fucose is an important component of many oligo- and polysaccharide structures as well as glycoproteins and glycolipids, which are often associated with a variety of physiological processes ranging from fertilization, embryogenesis, signal transduction, and disease progression, such as rheumatoid arthritis, inflammation, and cancer. 28103685 1 43 theme physiological 228:240 arg1 inflammation 371:382 inflammation 371:382 inflammation 371:382 Fucose is an important component of many oligo- and polysaccharide structures as well as glycoproteins and glycolipids, which are often associated with a variety of physiological processes ranging from fertilization, embryogenesis, signal transduction, and disease progression, such as rheumatoid arthritis, inflammation, and cancer. 28103685 1 43 theme physiological 228:240 arg1 cancer 389:394 cancer 389:394 cancer 389:394 Fucose is an important component of many oligo- and polysaccharide structures as well as glycoproteins and glycolipids, which are often associated with a variety of physiological processes ranging from fertilization, embryogenesis, signal transduction, and disease progression, such as rheumatoid arthritis, inflammation, and cancer. 28103685 1 43 theme physiological 228:240 arg1 arthritis 360:368 rheumatoid arthritis 349:368 rheumatoid arthritis 349:368 Fucose is an important component of many oligo- and polysaccharide structures as well as glycoproteins and glycolipids, which are often associated with a variety of physiological processes ranging from fertilization, embryogenesis, signal transduction, and disease progression, such as rheumatoid arthritis, inflammation, and cancer. 28103685 4 44 theme glycan 1083:1088 arg1 structures 1090:1099 well-defined glycan structures 1070:1099 well-defined glycan structures 1070:1099 Using BfFucH coupled with endoglycosidases and the emerging glycosynthases allows glycoengineering of IgG antibodies to provide homogeneous glycoforms with well-defined glycan structures and optimal effector functions. 28103685 3 45 theme fucosidic 804:812 arg1 linkages 814:821 the aforementioned fucosidic linkages 785:821 the aforementioned fucosidic linkages 785:821 Here, we report a highly efficient fucosidase, designated as BfFucH identified from a library of bacterial glycosidases expressed in E. coli from the CAZy database, which is capable of hydrolyzing the aforementioned fucosidic linkages, especially the α-1,6-linkage from the N-linked Fuc-α-1,6-GlcNAc residue on glycoproteins. 28103685 3 45 theme fucosidic 804:812 arg1 α-1,6-linkage 839:851 the α-1,6-linkage 835:851 especially the α-1,6-linkage 824:851 Here, we report a highly efficient fucosidase, designated as BfFucH identified from a library of bacterial glycosidases expressed in E. coli from the CAZy database, which is capable of hydrolyzing the aforementioned fucosidic linkages, especially the α-1,6-linkage from the N-linked Fuc-α-1,6-GlcNAc residue on glycoproteins. 28103685 1 46 theme processes 242:250 arg1 variety 217:223 a variety 215:223 a variety of physiological processes ranging from fertilization, embryogenesis, signal transduction, and disease progression, such as rheumatoid arthritis, inflammation, and cancer 215:394 Fucose is an important component of many oligo- and polysaccharide structures as well as glycoproteins and glycolipids, which are often associated with a variety of physiological processes ranging from fertilization, embryogenesis, signal transduction, and disease progression, such as rheumatoid arthritis, inflammation, and cancer. 28103685 1 46 theme processes 242:250 arg1 processes 242:250 physiological processes 228:250 physiological processes 228:250 Fucose is an important component of many oligo- and polysaccharide structures as well as glycoproteins and glycolipids, which are often associated with a variety of physiological processes ranging from fertilization, embryogenesis, signal transduction, and disease progression, such as rheumatoid arthritis, inflammation, and cancer. 28103685 1 46 theme processes 242:250 arg1 inflammation 371:382 inflammation 371:382 inflammation 371:382 Fucose is an important component of many oligo- and polysaccharide structures as well as glycoproteins and glycolipids, which are often associated with a variety of physiological processes ranging from fertilization, embryogenesis, signal transduction, and disease progression, such as rheumatoid arthritis, inflammation, and cancer. 28103685 1 46 theme processes 242:250 arg1 cancer 389:394 cancer 389:394 cancer 389:394 Fucose is an important component of many oligo- and polysaccharide structures as well as glycoproteins and glycolipids, which are often associated with a variety of physiological processes ranging from fertilization, embryogenesis, signal transduction, and disease progression, such as rheumatoid arthritis, inflammation, and cancer. 28103685 1 46 theme processes 242:250 arg1 arthritis 360:368 rheumatoid arthritis 349:368 rheumatoid arthritis 349:368 Fucose is an important component of many oligo- and polysaccharide structures as well as glycoproteins and glycolipids, which are often associated with a variety of physiological processes ranging from fertilization, embryogenesis, signal transduction, and disease progression, such as rheumatoid arthritis, inflammation, and cancer. 28049948 7 0 theme membrane 1163:1170 arg1 fraction 1172:1179 plasma membrane fraction 1156:1179 plasma membrane fraction 1156:1179 Western blot analysis revealed a 68 kDa band of WT-CRT protein in plasma membrane fraction, while G561R-mutant CRT protein predominantly showed bands at 55, 110 and 165 kDa in crude membrane fraction. 28049948 7 1 theme crude 1266:1270 arg1 fraction 1281:1288 crude membrane fraction 1266:1288 crude membrane fraction 1266:1288 Western blot analysis revealed a 68 kDa band of WT-CRT protein in plasma membrane fraction, while G561R-mutant CRT protein predominantly showed bands at 55, 110 and 165 kDa in crude membrane fraction. 28049948 9 2 theme cellular 1606:1613 arg1 localization 1615:1626 cellular localization 1606:1626 cellular localization 1606:1626 Our results suggest that the functional impairment of G561R-mutant CRT was probably caused by incomplete N-linked glycosylation due to misfolding during protein maturation, leading to oligomer formation and changes of cellular localization. 28049948 9 3 link N-linked 1493:1500 arg1 glycosylation 1502:1514 incomplete N-linked glycosylation 1482:1514 incomplete N-linked glycosylation due to misfolding during protein maturation 1482:1558 Our results suggest that the functional impairment of G561R-mutant CRT was probably caused by incomplete N-linked glycosylation due to misfolding during protein maturation, leading to oligomer formation and changes of cellular localization. 28049948 5 4 theme reduced 863:869 arg1 activity 890:897 greatly reduced creatine transport activity 855:897 greatly reduced creatine transport activity 855:897 G561R-mutant CRT exhibited greatly reduced creatine transport activity compared to wild-type CRT (WT-CRT) when expressed in 293 cells. 28049948 7 5 theme protein 1145:1151 arg1 band 1130:1133 a 68 kDa band 1121:1133 a 68 kDa band of WT-CRT protein in plasma membrane fraction 1121:1179 Western blot analysis revealed a 68 kDa band of WT-CRT protein in plasma membrane fraction, while G561R-mutant CRT protein predominantly showed bands at 55, 110 and 165 kDa in crude membrane fraction. 28049948 9 6 theme CRT 1455:1457 arg1 impairment 1428:1437 the functional impairment 1413:1437 the functional impairment of G561R-mutant CRT 1413:1457 Our results suggest that the functional impairment of G561R-mutant CRT was probably caused by incomplete N-linked glycosylation due to misfolding during protein maturation, leading to oligomer formation and changes of cellular localization. 28049948 1 7 theme blood-brain 342:352 arg1 barrier 354:360 the blood-brain barrier 338:360 the blood-brain barrier 338:360 Cerebral creatine deficiency syndromes (CCDSs) are caused by loss-of-function mutations in creatine transporter (CRT, SLC6A8), which transports creatine at the blood-brain barrier and into neurons of the central nervous system (CNS). 28049948 4 8 theme attenuation 815:825 arg1 mechanism 787:795 the mechanism 783:795 the mechanism of its functional attenuation 783:825 The purpose of the present study was to evaluate the reduction of creatine transport in G561R-mutant CRT-expressing 293 cells, and to clarify the mechanism of its functional attenuation. 28049948 5 9 theme creatine 871:878 arg1 activity 890:897 greatly reduced creatine transport activity 855:897 greatly reduced creatine transport activity 855:897 G561R-mutant CRT exhibited greatly reduced creatine transport activity compared to wild-type CRT (WT-CRT) when expressed in 293 cells. 28049948 1 10 theme creatine 273:280 arg1 transporter 282:292 creatine transporter 273:292 creatine transporter (CRT, SLC6A8) 273:306 Cerebral creatine deficiency syndromes (CCDSs) are caused by loss-of-function mutations in creatine transporter (CRT, SLC6A8), which transports creatine at the blood-brain barrier and into neurons of the central nervous system (CNS). 28049948 2 11 theme language 508:515 arg1 skills 517:522 poor language skills 503:522 poor language skills 503:522 This results in low cerebral creatine levels, and patients exhibit mental retardation, poor language skills and epilepsy. 28049948 6 12 located localized 991:999 arg2 protein 980:986 the mutant protein 969:986 the mutant protein 969:986 Also, the mutant protein is localized mainly in intracellular membrane fraction, while WT-CRT is localized in plasma membrane. 28049948 6 12 located localized 991:999 arg1 fraction 1034:1041 intracellular membrane fraction 1011:1041 intracellular membrane fraction 1011:1041 Also, the mutant protein is localized mainly in intracellular membrane fraction, while WT-CRT is localized in plasma membrane. 28049948 4 13 theme transport 716:724 arg1 reduction 694:702 the reduction 690:702 the reduction of creatine transport in G561R-mutant CRT-expressing 293 cells 690:765 The purpose of the present study was to evaluate the reduction of creatine transport in G561R-mutant CRT-expressing 293 cells, and to clarify the mechanism of its functional attenuation. 28049948 2 14 theme poor 503:506 arg1 skills 517:522 poor language skills 503:522 poor language skills 503:522 This results in low cerebral creatine levels, and patients exhibit mental retardation, poor language skills and epilepsy. 28049948 4 15 theme creatine 707:714 arg1 transport 716:724 creatine transport 707:724 creatine transport 707:724 The purpose of the present study was to evaluate the reduction of creatine transport in G561R-mutant CRT-expressing 293 cells, and to clarify the mechanism of its functional attenuation. 28049948 0 16 theme Creatine 106:113 arg1 Syndromes 126:134 Cerebral Creatine Deficiency Syndromes 97:134 Cerebral Creatine Deficiency Syndromes 97:134 Abnormal N-Glycosylation of a Novel Missense Creatine Transporter Mutant, G561R, Associated with Cerebral Creatine Deficiency Syndromes Alters Transporter Activity and Localization. 28049948 5 17 theme transport 880:888 arg1 activity 890:897 greatly reduced creatine transport activity 855:897 greatly reduced creatine transport activity 855:897 G561R-mutant CRT exhibited greatly reduced creatine transport activity compared to wild-type CRT (WT-CRT) when expressed in 293 cells. 28049948 4 18 theme G561R-mutant 729:740 arg1 cells 761:765 G561R-mutant CRT-expressing 293 cells 729:765 G561R-mutant CRT-expressing 293 cells 729:765 The purpose of the present study was to evaluate the reduction of creatine transport in G561R-mutant CRT-expressing 293 cells, and to clarify the mechanism of its functional attenuation. 28049948 5 19 theme G561R-mutant 828:839 arg1 CRT 841:843 G561R-mutant CRT 828:843 G561R-mutant CRT 828:843 G561R-mutant CRT exhibited greatly reduced creatine transport activity compared to wild-type CRT (WT-CRT) when expressed in 293 cells. 28049948 1 20 theme Cerebral 182:189 arg1 CCDSs 222:226 CCDSs 222:226 CCDSs 222:226 Cerebral creatine deficiency syndromes (CCDSs) are caused by loss-of-function mutations in creatine transporter (CRT, SLC6A8), which transports creatine at the blood-brain barrier and into neurons of the central nervous system (CNS). 28049948 1 20 theme Cerebral 182:189 arg1 syndromes 211:219 Cerebral creatine deficiency syndromes 182:219 Cerebral creatine deficiency syndromes (CCDSs) 182:227 Cerebral creatine deficiency syndromes (CCDSs) are caused by loss-of-function mutations in creatine transporter (CRT, SLC6A8), which transports creatine at the blood-brain barrier and into neurons of the central nervous system (CNS). 28049948 0 21 theme Cerebral 97:104 arg1 Syndromes 126:134 Cerebral Creatine Deficiency Syndromes 97:134 Cerebral Creatine Deficiency Syndromes 97:134 Abnormal N-Glycosylation of a Novel Missense Creatine Transporter Mutant, G561R, Associated with Cerebral Creatine Deficiency Syndromes Alters Transporter Activity and Localization. 28049948 7 22 from band 1130:1133 arg1 fraction 1172:1179 plasma membrane fraction 1156:1179 plasma membrane fraction 1156:1179 Western blot analysis revealed a 68 kDa band of WT-CRT protein in plasma membrane fraction, while G561R-mutant CRT protein predominantly showed bands at 55, 110 and 165 kDa in crude membrane fraction. 28049948 1 23 theme creatine 191:198 arg1 CCDSs 222:226 CCDSs 222:226 CCDSs 222:226 Cerebral creatine deficiency syndromes (CCDSs) are caused by loss-of-function mutations in creatine transporter (CRT, SLC6A8), which transports creatine at the blood-brain barrier and into neurons of the central nervous system (CNS). 28049948 1 23 theme creatine 191:198 arg1 syndromes 211:219 Cerebral creatine deficiency syndromes 182:219 Cerebral creatine deficiency syndromes (CCDSs) 182:227 Cerebral creatine deficiency syndromes (CCDSs) are caused by loss-of-function mutations in creatine transporter (CRT, SLC6A8), which transports creatine at the blood-brain barrier and into neurons of the central nervous system (CNS). 28049948 2 24 theme low 432:434 arg1 levels 454:459 low cerebral creatine levels 432:459 low cerebral creatine levels 432:459 This results in low cerebral creatine levels, and patients exhibit mental retardation, poor language skills and epilepsy. 28049948 4 25 theme functional 804:813 arg1 attenuation 815:825 its functional attenuation 800:825 its functional attenuation 800:825 The purpose of the present study was to evaluate the reduction of creatine transport in G561R-mutant CRT-expressing 293 cells, and to clarify the mechanism of its functional attenuation. 28049948 4 26 from reduction 694:702 arg1 cells 761:765 G561R-mutant CRT-expressing 293 cells 729:765 G561R-mutant CRT-expressing 293 cells 729:765 The purpose of the present study was to evaluate the reduction of creatine transport in G561R-mutant CRT-expressing 293 cells, and to clarify the mechanism of its functional attenuation. 28049948 5 27 theme wild-type 911:919 arg1 WT-CRT 926:931 WT-CRT 926:931 WT-CRT 926:931 G561R-mutant CRT exhibited greatly reduced creatine transport activity compared to wild-type CRT (WT-CRT) when expressed in 293 cells. 28049948 5 27 theme wild-type 911:919 arg1 CRT 921:923 wild-type CRT 911:923 wild-type CRT (WT-CRT) 911:932 G561R-mutant CRT exhibited greatly reduced creatine transport activity compared to wild-type CRT (WT-CRT) when expressed in 293 cells. 28049948 9 28 theme oligomer 1572:1579 arg1 formation 1581:1589 oligomer formation 1572:1589 oligomer formation 1572:1589 Our results suggest that the functional impairment of G561R-mutant CRT was probably caused by incomplete N-linked glycosylation due to misfolding during protein maturation, leading to oligomer formation and changes of cellular localization. 28049948 1 29 theme deficiency 200:209 arg1 CCDSs 222:226 CCDSs 222:226 CCDSs 222:226 Cerebral creatine deficiency syndromes (CCDSs) are caused by loss-of-function mutations in creatine transporter (CRT, SLC6A8), which transports creatine at the blood-brain barrier and into neurons of the central nervous system (CNS). 28049948 1 29 theme deficiency 200:209 arg1 syndromes 211:219 Cerebral creatine deficiency syndromes 182:219 Cerebral creatine deficiency syndromes (CCDSs) 182:227 Cerebral creatine deficiency syndromes (CCDSs) are caused by loss-of-function mutations in creatine transporter (CRT, SLC6A8), which transports creatine at the blood-brain barrier and into neurons of the central nervous system (CNS). 28049948 0 30 theme Abnormal 0:7 arg1 N-Glycosylation 9:23 Abnormal N-Glycosylation 0:23 Abnormal N-Glycosylation of a Novel Missense Creatine Transporter Mutant, G561R, Associated with Cerebral Creatine Deficiency Syndromes 0:134 Abnormal N-Glycosylation of a Novel Missense Creatine Transporter Mutant, G561R, Associated with Cerebral Creatine Deficiency Syndromes Alters Transporter Activity and Localization. 28049948 3 31 theme novel 554:558 arg1 mutation 584:591 a novel human CRT gene missense mutation 552:591 a novel human CRT gene missense mutation (c.1681 G>C, G561R) 552:611 We identified a novel human CRT gene missense mutation (c.1681 G>C, G561R) in Japanese CCDSs patients. 28049948 6 32 located localized 1060:1068 arg1 membrane 1080:1087 plasma membrane 1073:1087 plasma membrane 1073:1087 Also, the mutant protein is localized mainly in intracellular membrane fraction, while WT-CRT is localized in plasma membrane. 28049948 6 32 located localized 1060:1068 arg2 WT-CRT 1050:1055 WT-CRT 1050:1055 WT-CRT 1050:1055 Also, the mutant protein is localized mainly in intracellular membrane fraction, while WT-CRT is localized in plasma membrane. 28049948 7 33 from 55 1243:1244 arg1 bands 1234:1238 bands 1234:1238 bands at 55, 110 and 165 kDa in crude membrane fraction 1234:1288 Western blot analysis revealed a 68 kDa band of WT-CRT protein in plasma membrane fraction, while G561R-mutant CRT protein predominantly showed bands at 55, 110 and 165 kDa in crude membrane fraction. 28049948 7 33 from 55 1243:1244 arg1 fraction 1281:1288 crude membrane fraction 1266:1288 crude membrane fraction 1266:1288 Western blot analysis revealed a 68 kDa band of WT-CRT protein in plasma membrane fraction, while G561R-mutant CRT protein predominantly showed bands at 55, 110 and 165 kDa in crude membrane fraction. 28049948 8 34 theme G561R-mutant 1320:1331 arg1 CRT 1333:1335 both WT-CRT and G561R-mutant CRT 1304:1335 both WT-CRT and G561R-mutant CRT 1304:1335 The bands of both WT-CRT and G561R-mutant CRT were shifted to 50 kDa by N-glycosidase treatment. 28049948 3 35 dep mutation 584:591 arg1 G561R 606:610 G561R 606:610 G561R 606:610 We identified a novel human CRT gene missense mutation (c.1681 G>C, G561R) in Japanese CCDSs patients. 28049948 3 35 dep mutation 584:591 arg1 G>C 601:603 c.1681 G>C 594:603 c.1681 G>C 594:603 We identified a novel human CRT gene missense mutation (c.1681 G>C, G561R) in Japanese CCDSs patients. 28049948 7 36 theme 68 kDa 1123:1128 arg1 band 1130:1133 a 68 kDa band 1121:1133 a 68 kDa band of WT-CRT protein in plasma membrane fraction 1121:1179 Western blot analysis revealed a 68 kDa band of WT-CRT protein in plasma membrane fraction, while G561R-mutant CRT protein predominantly showed bands at 55, 110 and 165 kDa in crude membrane fraction. 28049948 9 37 theme functional 1417:1426 arg1 impairment 1428:1437 the functional impairment 1413:1437 the functional impairment of G561R-mutant CRT 1413:1457 Our results suggest that the functional impairment of G561R-mutant CRT was probably caused by incomplete N-linked glycosylation due to misfolding during protein maturation, leading to oligomer formation and changes of cellular localization. 28049948 0 38 theme Deficiency 115:124 arg1 Syndromes 126:134 Cerebral Creatine Deficiency Syndromes 97:134 Cerebral Creatine Deficiency Syndromes 97:134 Abnormal N-Glycosylation of a Novel Missense Creatine Transporter Mutant, G561R, Associated with Cerebral Creatine Deficiency Syndromes Alters Transporter Activity and Localization. 28049948 8 39 theme CRT 1333:1335 arg1 bands 1295:1299 The bands 1291:1299 The bands of both WT-CRT and G561R-mutant CRT 1291:1335 The bands of both WT-CRT and G561R-mutant CRT were shifted to 50 kDa by N-glycosidase treatment. 28049948 7 40 theme CRT 1201:1203 arg1 protein 1205:1211 G561R-mutant CRT protein 1188:1211 G561R-mutant CRT protein 1188:1211 Western blot analysis revealed a 68 kDa band of WT-CRT protein in plasma membrane fraction, while G561R-mutant CRT protein predominantly showed bands at 55, 110 and 165 kDa in crude membrane fraction. 28049948 2 41 theme creatine 445:452 arg1 levels 454:459 low cerebral creatine levels 432:459 low cerebral creatine levels 432:459 This results in low cerebral creatine levels, and patients exhibit mental retardation, poor language skills and epilepsy. 28049948 0 42 theme Missense 36:43 arg1 G561R 74:78 G561R 74:78 G561R 74:78 Abnormal N-Glycosylation of a Novel Missense Creatine Transporter Mutant, G561R, Associated with Cerebral Creatine Deficiency Syndromes Alters Transporter Activity and Localization. 28049948 0 42 theme Missense 36:43 arg1 Mutant 66:71 a Novel Missense Creatine Transporter Mutant 28:71 a Novel Missense Creatine Transporter Mutant 28:71 Abnormal N-Glycosylation of a Novel Missense Creatine Transporter Mutant, G561R, Associated with Cerebral Creatine Deficiency Syndromes Alters Transporter Activity and Localization. 28049948 9 43 theme G561R-mutant 1442:1453 arg1 CRT 1455:1457 G561R-mutant CRT 1442:1457 G561R-mutant CRT 1442:1457 Our results suggest that the functional impairment of G561R-mutant CRT was probably caused by incomplete N-linked glycosylation due to misfolding during protein maturation, leading to oligomer formation and changes of cellular localization. 28049948 0 44 theme Transporter 143:153 arg1 Activity 155:162 Transporter Activity 143:162 Transporter Activity 143:162 Abnormal N-Glycosylation of a Novel Missense Creatine Transporter Mutant, G561R, Associated with Cerebral Creatine Deficiency Syndromes Alters Transporter Activity and Localization. 28049948 1 45 theme central 386:392 arg1 CNS 410:412 CNS 410:412 CNS 410:412 Cerebral creatine deficiency syndromes (CCDSs) are caused by loss-of-function mutations in creatine transporter (CRT, SLC6A8), which transports creatine at the blood-brain barrier and into neurons of the central nervous system (CNS). 28049948 1 45 theme central 386:392 arg1 system 402:407 the central nervous system 382:407 the central nervous system (CNS) 382:413 Cerebral creatine deficiency syndromes (CCDSs) are caused by loss-of-function mutations in creatine transporter (CRT, SLC6A8), which transports creatine at the blood-brain barrier and into neurons of the central nervous system (CNS). 28049948 3 46 theme gene 570:573 arg1 mutation 584:591 a novel human CRT gene missense mutation 552:591 a novel human CRT gene missense mutation (c.1681 G>C, G561R) 552:611 We identified a novel human CRT gene missense mutation (c.1681 G>C, G561R) in Japanese CCDSs patients. 28049948 6 47 theme intracellular 1011:1023 arg1 fraction 1034:1041 intracellular membrane fraction 1011:1041 intracellular membrane fraction 1011:1041 Also, the mutant protein is localized mainly in intracellular membrane fraction, while WT-CRT is localized in plasma membrane. 28049948 7 48 theme Western 1090:1096 arg1 analysis 1103:1110 Western blot analysis 1090:1110 Western blot analysis 1090:1110 Western blot analysis revealed a 68 kDa band of WT-CRT protein in plasma membrane fraction, while G561R-mutant CRT protein predominantly showed bands at 55, 110 and 165 kDa in crude membrane fraction. 28049948 1 49 from barrier 354:360 arg1 creatine 326:333 creatine 326:333 creatine at the blood-brain barrier and into neurons of the central nervous system (CNS) 326:413 Cerebral creatine deficiency syndromes (CCDSs) are caused by loss-of-function mutations in creatine transporter (CRT, SLC6A8), which transports creatine at the blood-brain barrier and into neurons of the central nervous system (CNS). 28049948 0 50 theme Novel 30:34 arg1 G561R 74:78 G561R 74:78 G561R 74:78 Abnormal N-Glycosylation of a Novel Missense Creatine Transporter Mutant, G561R, Associated with Cerebral Creatine Deficiency Syndromes Alters Transporter Activity and Localization. 28049948 0 50 theme Novel 30:34 arg1 Mutant 66:71 a Novel Missense Creatine Transporter Mutant 28:71 a Novel Missense Creatine Transporter Mutant 28:71 Abnormal N-Glycosylation of a Novel Missense Creatine Transporter Mutant, G561R, Associated with Cerebral Creatine Deficiency Syndromes Alters Transporter Activity and Localization. 28049948 1 51 theme nervous 394:400 arg1 CNS 410:412 CNS 410:412 CNS 410:412 Cerebral creatine deficiency syndromes (CCDSs) are caused by loss-of-function mutations in creatine transporter (CRT, SLC6A8), which transports creatine at the blood-brain barrier and into neurons of the central nervous system (CNS). 28049948 1 51 theme nervous 394:400 arg1 system 402:407 the central nervous system 382:407 the central nervous system (CNS) 382:413 Cerebral creatine deficiency syndromes (CCDSs) are caused by loss-of-function mutations in creatine transporter (CRT, SLC6A8), which transports creatine at the blood-brain barrier and into neurons of the central nervous system (CNS). 28049948 0 52 gly N-Glycosylation 9:23 arg1 G561R 74:78 G561R 74:78 G561R 74:78 Abnormal N-Glycosylation of a Novel Missense Creatine Transporter Mutant, G561R, Associated with Cerebral Creatine Deficiency Syndromes Alters Transporter Activity and Localization. 28049948 0 52 gly N-Glycosylation 9:23 arg1 Mutant 66:71 a Novel Missense Creatine Transporter Mutant 28:71 a Novel Missense Creatine Transporter Mutant 28:71 Abnormal N-Glycosylation of a Novel Missense Creatine Transporter Mutant, G561R, Associated with Cerebral Creatine Deficiency Syndromes Alters Transporter Activity and Localization. 28049948 6 53 theme membrane 1025:1032 arg1 fraction 1034:1041 intracellular membrane fraction 1011:1041 intracellular membrane fraction 1011:1041 Also, the mutant protein is localized mainly in intracellular membrane fraction, while WT-CRT is localized in plasma membrane. 28049948 0 54 theme Transporter 54:64 arg1 G561R 74:78 G561R 74:78 G561R 74:78 Abnormal N-Glycosylation of a Novel Missense Creatine Transporter Mutant, G561R, Associated with Cerebral Creatine Deficiency Syndromes Alters Transporter Activity and Localization. 28049948 0 54 theme Transporter 54:64 arg1 Mutant 66:71 a Novel Missense Creatine Transporter Mutant 28:71 a Novel Missense Creatine Transporter Mutant 28:71 Abnormal N-Glycosylation of a Novel Missense Creatine Transporter Mutant, G561R, Associated with Cerebral Creatine Deficiency Syndromes Alters Transporter Activity and Localization. 28049948 8 55 theme WT-CRT 1309:1314 arg1 CRT 1333:1335 both WT-CRT and G561R-mutant CRT 1304:1335 both WT-CRT and G561R-mutant CRT 1304:1335 The bands of both WT-CRT and G561R-mutant CRT were shifted to 50 kDa by N-glycosidase treatment. 28049948 1 56 theme system 402:407 arg1 neurons 371:377 neurons 371:377 neurons of the central nervous system (CNS) 371:413 Cerebral creatine deficiency syndromes (CCDSs) are caused by loss-of-function mutations in creatine transporter (CRT, SLC6A8), which transports creatine at the blood-brain barrier and into neurons of the central nervous system (CNS). 28049948 3 57 theme human 560:564 arg1 mutation 584:591 a novel human CRT gene missense mutation 552:591 a novel human CRT gene missense mutation (c.1681 G>C, G561R) 552:611 We identified a novel human CRT gene missense mutation (c.1681 G>C, G561R) in Japanese CCDSs patients. 28049948 4 58 theme study 668:672 arg1 purpose 645:651 The purpose 641:651 The purpose of the present study 641:672 The purpose of the present study was to evaluate the reduction of creatine transport in G561R-mutant CRT-expressing 293 cells, and to clarify the mechanism of its functional attenuation. 28049948 0 59 theme Creatine 45:52 arg1 G561R 74:78 G561R 74:78 G561R 74:78 Abnormal N-Glycosylation of a Novel Missense Creatine Transporter Mutant, G561R, Associated with Cerebral Creatine Deficiency Syndromes Alters Transporter Activity and Localization. 28049948 0 59 theme Creatine 45:52 arg1 Mutant 66:71 a Novel Missense Creatine Transporter Mutant 28:71 a Novel Missense Creatine Transporter Mutant 28:71 Abnormal N-Glycosylation of a Novel Missense Creatine Transporter Mutant, G561R, Associated with Cerebral Creatine Deficiency Syndromes Alters Transporter Activity and Localization. 28049948 9 60 theme incomplete 1482:1491 arg1 glycosylation 1502:1514 incomplete N-linked glycosylation 1482:1514 incomplete N-linked glycosylation due to misfolding during protein maturation 1482:1558 Our results suggest that the functional impairment of G561R-mutant CRT was probably caused by incomplete N-linked glycosylation due to misfolding during protein maturation, leading to oligomer formation and changes of cellular localization. 28049948 1 61 from mutations 260:268 arg1 transporter 282:292 creatine transporter 273:292 creatine transporter (CRT, SLC6A8) 273:306 Cerebral creatine deficiency syndromes (CCDSs) are caused by loss-of-function mutations in creatine transporter (CRT, SLC6A8), which transports creatine at the blood-brain barrier and into neurons of the central nervous system (CNS). 28049948 1 62 dep transporter 282:292 arg1 SLC6A8 300:305 SLC6A8 300:305 SLC6A8 300:305 Cerebral creatine deficiency syndromes (CCDSs) are caused by loss-of-function mutations in creatine transporter (CRT, SLC6A8), which transports creatine at the blood-brain barrier and into neurons of the central nervous system (CNS). 28049948 1 62 dep transporter 282:292 arg1 CRT 295:297 CRT 295:297 CRT 295:297 Cerebral creatine deficiency syndromes (CCDSs) are caused by loss-of-function mutations in creatine transporter (CRT, SLC6A8), which transports creatine at the blood-brain barrier and into neurons of the central nervous system (CNS). 28049948 3 63 theme CRT 566:568 arg1 mutation 584:591 a novel human CRT gene missense mutation 552:591 a novel human CRT gene missense mutation (c.1681 G>C, G561R) 552:611 We identified a novel human CRT gene missense mutation (c.1681 G>C, G561R) in Japanese CCDSs patients. 28049948 4 64 theme present 660:666 arg1 study 668:672 the present study 656:672 the present study 656:672 The purpose of the present study was to evaluate the reduction of creatine transport in G561R-mutant CRT-expressing 293 cells, and to clarify the mechanism of its functional attenuation. 28049948 9 65 theme localization 1615:1626 arg1 changes 1595:1601 changes 1595:1601 changes of cellular localization 1595:1626 Our results suggest that the functional impairment of G561R-mutant CRT was probably caused by incomplete N-linked glycosylation due to misfolding during protein maturation, leading to oligomer formation and changes of cellular localization. 28049948 9 65 theme localization 1615:1626 arg1 formation 1581:1589 oligomer formation 1572:1589 oligomer formation 1572:1589 Our results suggest that the functional impairment of G561R-mutant CRT was probably caused by incomplete N-linked glycosylation due to misfolding during protein maturation, leading to oligomer formation and changes of cellular localization. 28049948 7 66 theme membrane 1272:1279 arg1 fraction 1281:1288 crude membrane fraction 1266:1288 crude membrane fraction 1266:1288 Western blot analysis revealed a 68 kDa band of WT-CRT protein in plasma membrane fraction, while G561R-mutant CRT protein predominantly showed bands at 55, 110 and 165 kDa in crude membrane fraction. 28049948 7 67 theme blot 1098:1101 arg1 analysis 1103:1110 Western blot analysis 1090:1110 Western blot analysis 1090:1110 Western blot analysis revealed a 68 kDa band of WT-CRT protein in plasma membrane fraction, while G561R-mutant CRT protein predominantly showed bands at 55, 110 and 165 kDa in crude membrane fraction. 28049948 3 68 theme missense 575:582 arg1 mutation 584:591 a novel human CRT gene missense mutation 552:591 a novel human CRT gene missense mutation (c.1681 G>C, G561R) 552:611 We identified a novel human CRT gene missense mutation (c.1681 G>C, G561R) in Japanese CCDSs patients. 28049948 6 69 theme plasma 1073:1078 arg1 membrane 1080:1087 plasma membrane 1073:1087 plasma membrane 1073:1087 Also, the mutant protein is localized mainly in intracellular membrane fraction, while WT-CRT is localized in plasma membrane. 28049948 9 70 theme protein 1541:1547 arg1 maturation 1549:1558 protein maturation 1541:1558 protein maturation 1541:1558 Our results suggest that the functional impairment of G561R-mutant CRT was probably caused by incomplete N-linked glycosylation due to misfolding during protein maturation, leading to oligomer formation and changes of cellular localization. 28049948 7 71 from 165 kDa 1255:1261 arg1 bands 1234:1238 bands 1234:1238 bands at 55, 110 and 165 kDa in crude membrane fraction 1234:1288 Western blot analysis revealed a 68 kDa band of WT-CRT protein in plasma membrane fraction, while G561R-mutant CRT protein predominantly showed bands at 55, 110 and 165 kDa in crude membrane fraction. 28049948 3 72 theme Japanese 616:623 arg1 patients 631:638 Japanese CCDSs patients 616:638 Japanese CCDSs patients 616:638 We identified a novel human CRT gene missense mutation (c.1681 G>C, G561R) in Japanese CCDSs patients. 28049948 4 73 theme CRT-expressing 742:755 arg1 cells 761:765 G561R-mutant CRT-expressing 293 cells 729:765 G561R-mutant CRT-expressing 293 cells 729:765 The purpose of the present study was to evaluate the reduction of creatine transport in G561R-mutant CRT-expressing 293 cells, and to clarify the mechanism of its functional attenuation. 28049948 2 74 theme cerebral 436:443 arg1 levels 454:459 low cerebral creatine levels 432:459 low cerebral creatine levels 432:459 This results in low cerebral creatine levels, and patients exhibit mental retardation, poor language skills and epilepsy. 28049948 6 75 theme mutant 973:978 arg1 protein 980:986 the mutant protein 969:986 the mutant protein 969:986 Also, the mutant protein is localized mainly in intracellular membrane fraction, while WT-CRT is localized in plasma membrane. 28049948 2 76 theme mental 483:488 arg1 retardation 490:500 mental retardation 483:500 mental retardation 483:500 This results in low cerebral creatine levels, and patients exhibit mental retardation, poor language skills and epilepsy. 28049948 3 77 theme CCDSs 625:629 arg1 patients 631:638 Japanese CCDSs patients 616:638 Japanese CCDSs patients 616:638 We identified a novel human CRT gene missense mutation (c.1681 G>C, G561R) in Japanese CCDSs patients. 28049948 1 78 theme loss-of-function 243:258 arg1 mutations 260:268 loss-of-function mutations 243:268 loss-of-function mutations in creatine transporter (CRT, SLC6A8), which transports creatine at the blood-brain barrier and into neurons of the central nervous system (CNS) 243:413 Cerebral creatine deficiency syndromes (CCDSs) are caused by loss-of-function mutations in creatine transporter (CRT, SLC6A8), which transports creatine at the blood-brain barrier and into neurons of the central nervous system (CNS). 28049948 0 79 theme Mutant 66:71 arg1 N-Glycosylation 9:23 Abnormal N-Glycosylation 0:23 Abnormal N-Glycosylation of a Novel Missense Creatine Transporter Mutant, G561R, Associated with Cerebral Creatine Deficiency Syndromes 0:134 Abnormal N-Glycosylation of a Novel Missense Creatine Transporter Mutant, G561R, Associated with Cerebral Creatine Deficiency Syndromes Alters Transporter Activity and Localization. 28049948 7 80 theme WT-CRT 1138:1143 arg1 protein 1145:1151 WT-CRT protein 1138:1151 WT-CRT protein 1138:1151 Western blot analysis revealed a 68 kDa band of WT-CRT protein in plasma membrane fraction, while G561R-mutant CRT protein predominantly showed bands at 55, 110 and 165 kDa in crude membrane fraction. 28049948 8 81 theme N-glycosidase 1363:1375 arg1 treatment 1377:1385 N-glycosidase treatment 1363:1385 N-glycosidase treatment 1363:1385 The bands of both WT-CRT and G561R-mutant CRT were shifted to 50 kDa by N-glycosidase treatment. 28049948 9 82 theme N-linked 1493:1500 arg1 glycosylation 1502:1514 incomplete N-linked glycosylation 1482:1514 incomplete N-linked glycosylation due to misfolding during protein maturation 1482:1558 Our results suggest that the functional impairment of G561R-mutant CRT was probably caused by incomplete N-linked glycosylation due to misfolding during protein maturation, leading to oligomer formation and changes of cellular localization. 28049948 7 83 theme G561R-mutant 1188:1199 arg1 protein 1205:1211 G561R-mutant CRT protein 1188:1211 G561R-mutant CRT protein 1188:1211 Western blot analysis revealed a 68 kDa band of WT-CRT protein in plasma membrane fraction, while G561R-mutant CRT protein predominantly showed bands at 55, 110 and 165 kDa in crude membrane fraction. 28049948 7 84 theme plasma 1156:1161 arg1 fraction 1172:1179 plasma membrane fraction 1156:1179 plasma membrane fraction 1156:1179 Western blot analysis revealed a 68 kDa band of WT-CRT protein in plasma membrane fraction, while G561R-mutant CRT protein predominantly showed bands at 55, 110 and 165 kDa in crude membrane fraction. 25605972 10 0 theme potential 1314:1322 arg1 mechanism 1324:1332 a potential mechanism 1312:1332 a potential mechanism for the regulation of ALK activity in vivo 1312:1375 Thus, heparin and perhaps related glycosaminoglycans function as ligands for ALK, revealing a potential mechanism for the regulation of ALK activity in vivo and suggesting an approach for developing ALK-targeted therapies for cancer. 25605972 10 1 theme ALK 1356:1358 arg1 activity 1360:1367 ALK activity 1356:1367 ALK activity 1356:1367 Thus, heparin and perhaps related glycosaminoglycans function as ligands for ALK, revealing a potential mechanism for the regulation of ALK activity in vivo and suggesting an approach for developing ALK-targeted therapies for cancer. 25605972 0 2 theme kinase 64:69 arg1 ALK 71:73 tyrosine kinase ALK 55:73 the orphan receptor tyrosine kinase ALK 35:73 Heparin is an activating ligand of the orphan receptor tyrosine kinase ALK. 25605972 4 3 theme disease 463:469 arg1 progression 471:481 disease progression 463:481 disease progression 463:481 Increased activation of RTKs by mutation, genetic amplification, or signals from the stroma contributes to disease progression and acquired drug resistance in cancer. 25605972 8 4 theme different 1024:1032 arg1 patterns 1015:1022 sulfation patterns 1005:1022 sulfation patterns different than heparin 1005:1045 Heparin lacking N- and O-linked sulfate groups or other glycosaminoglycans with sulfation patterns different than heparin failed to activate ALK. 25605972 7 5 theme cultured 895:902 arg1 cells 918:922 cultured neuroblastoma cells 895:922 cultured neuroblastoma cells 895:922 Whereas heparins with short chain lengths bound to ALK in a monovalent manner and did not activate the receptor, longer heparin chains induced ALK dimerization and activation in cultured neuroblastoma cells. 25605972 1 6 theme few 123:125 arg1 RTKs 173:176 RTKs 173:176 RTKs 173:176 Anaplastic lymphoma kinase (ALK) is one of the few remaining "orphan" receptor tyrosine kinases (RTKs) in which the ligands are unknown. 25605972 1 6 theme few 123:125 arg1 kinases 164:170 the few remaining "orphan" receptor tyrosine kinases 119:170 the few remaining "orphan" receptor tyrosine kinases (RTKs) 119:177 Anaplastic lymphoma kinase (ALK) is one of the few remaining "orphan" receptor tyrosine kinases (RTKs) in which the ligands are unknown. 25605972 9 7 theme heparin-mediated 1184:1199 arg1 activation 1201:1210 heparin-mediated activation 1184:1210 heparin-mediated activation of ALK 1184:1217 Moreover, antibodies that bound to the extracellular domain of ALK interfered with heparin binding and prevented heparin-mediated activation of ALK. 25605972 5 8 theme other 611:615 arg1 cancers 617:623 other cancers 611:623 other cancers 611:623 Aberrant activation of ALK occurs in subsets of lung adenocarcinoma, neuroblastoma, and other cancers. 25605972 7 9 theme neuroblastoma 904:916 arg1 cells 918:922 cultured neuroblastoma cells 895:922 cultured neuroblastoma cells 895:922 Whereas heparins with short chain lengths bound to ALK in a monovalent manner and did not activate the receptor, longer heparin chains induced ALK dimerization and activation in cultured neuroblastoma cells. 25605972 2 10 theme RTKs 243:246 arg1 activation 229:238 Ligand-mediated activation 213:238 Ligand-mediated activation of RTKs 213:246 Ligand-mediated activation of RTKs is important throughout development. 25605972 4 11 from stroma 441:446 arg1 mutation 388:395 mutation 388:395 mutation 388:395 Increased activation of RTKs by mutation, genetic amplification, or signals from the stroma contributes to disease progression and acquired drug resistance in cancer. 25605972 4 11 from stroma 441:446 arg1 amplification 406:418 genetic amplification 398:418 genetic amplification 398:418 Increased activation of RTKs by mutation, genetic amplification, or signals from the stroma contributes to disease progression and acquired drug resistance in cancer. 25605972 4 11 from stroma 441:446 arg1 signals 424:430 signals 424:430 signals from the stroma 424:446 Increased activation of RTKs by mutation, genetic amplification, or signals from the stroma contributes to disease progression and acquired drug resistance in cancer. 25605972 1 12 from one 112:114 arg1 ligands 192:198 the ligands 188:198 the ligands 188:198 Anaplastic lymphoma kinase (ALK) is one of the few remaining "orphan" receptor tyrosine kinases (RTKs) in which the ligands are unknown. 25605972 1 12 from one 112:114 arg1 unknown 204:210 unknown 204:210 unknown 204:210 Anaplastic lymphoma kinase (ALK) is one of the few remaining "orphan" receptor tyrosine kinases (RTKs) in which the ligands are unknown. 25605972 8 13 with glycosaminoglycans 981:998 arg1 patterns 1015:1022 sulfation patterns 1005:1022 sulfation patterns different than heparin 1005:1045 Heparin lacking N- and O-linked sulfate groups or other glycosaminoglycans with sulfation patterns different than heparin failed to activate ALK. 25605972 5 14 theme lung 571:574 arg1 adenocarcinoma 576:589 lung adenocarcinoma 571:589 lung adenocarcinoma 571:589 Aberrant activation of ALK occurs in subsets of lung adenocarcinoma, neuroblastoma, and other cancers. 25605972 4 15 theme Increased 356:364 arg1 activation 366:375 Increased activation 356:375 Increased activation of RTKs by mutation, genetic amplification, or signals from the stroma 356:446 Increased activation of RTKs by mutation, genetic amplification, or signals from the stroma contributes to disease progression and acquired drug resistance in cancer. 25605972 2 16 theme Ligand-mediated 213:227 arg1 activation 229:238 Ligand-mediated activation 213:238 Ligand-mediated activation of RTKs 213:246 Ligand-mediated activation of RTKs is important throughout development. 25605972 10 17 theme related 1246:1252 arg1 glycosaminoglycans 1254:1271 perhaps related glycosaminoglycans 1238:1271 perhaps related glycosaminoglycans 1238:1271 Thus, heparin and perhaps related glycosaminoglycans function as ligands for ALK, revealing a potential mechanism for the regulation of ALK activity in vivo and suggesting an approach for developing ALK-targeted therapies for cancer. 25605972 10 17 theme related 1246:1252 arg1 ligands 1285:1291 ligands 1285:1291 ligands for ALK 1285:1299 Thus, heparin and perhaps related glycosaminoglycans function as ligands for ALK, revealing a potential mechanism for the regulation of ALK activity in vivo and suggesting an approach for developing ALK-targeted therapies for cancer. 25605972 10 17 theme related 1246:1252 arg1 heparin 1226:1232 heparin 1226:1232 heparin 1226:1232 Thus, heparin and perhaps related glycosaminoglycans function as ligands for ALK, revealing a potential mechanism for the regulation of ALK activity in vivo and suggesting an approach for developing ALK-targeted therapies for cancer. 25605972 1 18 theme remaining 127:135 arg1 RTKs 173:176 RTKs 173:176 RTKs 173:176 Anaplastic lymphoma kinase (ALK) is one of the few remaining "orphan" receptor tyrosine kinases (RTKs) in which the ligands are unknown. 25605972 1 18 theme remaining 127:135 arg1 kinases 164:170 the few remaining "orphan" receptor tyrosine kinases 119:170 the few remaining "orphan" receptor tyrosine kinases (RTKs) 119:177 Anaplastic lymphoma kinase (ALK) is one of the few remaining "orphan" receptor tyrosine kinases (RTKs) in which the ligands are unknown. 25605972 5 19 theme adenocarcinoma 576:589 arg1 subsets 560:566 subsets 560:566 subsets of lung adenocarcinoma, neuroblastoma, and other cancers 560:623 Aberrant activation of ALK occurs in subsets of lung adenocarcinoma, neuroblastoma, and other cancers. 25605972 5 20 theme Aberrant 523:530 arg1 activation 532:541 Aberrant activation 523:541 Aberrant activation of ALK 523:548 Aberrant activation of ALK occurs in subsets of lung adenocarcinoma, neuroblastoma, and other cancers. 25605972 7 21 theme monovalent 777:786 arg1 manner 788:793 a monovalent manner 775:793 a monovalent manner 775:793 Whereas heparins with short chain lengths bound to ALK in a monovalent manner and did not activate the receptor, longer heparin chains induced ALK dimerization and activation in cultured neuroblastoma cells. 25605972 8 22 theme other 975:979 arg1 glycosaminoglycans 981:998 other glycosaminoglycans 975:998 other glycosaminoglycans with sulfation patterns different than heparin 975:1045 Heparin lacking N- and O-linked sulfate groups or other glycosaminoglycans with sulfation patterns different than heparin failed to activate ALK. 25605972 7 23 theme ALK 860:862 arg1 dimerization 864:875 ALK dimerization 860:875 ALK dimerization 860:875 Whereas heparins with short chain lengths bound to ALK in a monovalent manner and did not activate the receptor, longer heparin chains induced ALK dimerization and activation in cultured neuroblastoma cells. 25605972 1 24 theme orphan 138:143 arg1 RTKs 173:176 RTKs 173:176 RTKs 173:176 Anaplastic lymphoma kinase (ALK) is one of the few remaining "orphan" receptor tyrosine kinases (RTKs) in which the ligands are unknown. 25605972 1 24 theme orphan 138:143 arg1 kinases 164:170 the few remaining "orphan" receptor tyrosine kinases 119:170 the few remaining "orphan" receptor tyrosine kinases (RTKs) 119:177 Anaplastic lymphoma kinase (ALK) is one of the few remaining "orphan" receptor tyrosine kinases (RTKs) in which the ligands are unknown. 25605972 3 25 theme nervous 340:346 arg1 system 348:353 the nervous system 336:353 the nervous system 336:353 ALK is particularly relevant to the development of the nervous system. 25605972 5 26 theme neuroblastoma 592:604 arg1 subsets 560:566 subsets 560:566 subsets of lung adenocarcinoma, neuroblastoma, and other cancers 560:623 Aberrant activation of ALK occurs in subsets of lung adenocarcinoma, neuroblastoma, and other cancers. 25605972 8 27 theme sulfate 957:963 arg1 groups 965:970 O-linked sulfate groups 948:970 O-linked sulfate groups 948:970 Heparin lacking N- and O-linked sulfate groups or other glycosaminoglycans with sulfation patterns different than heparin failed to activate ALK. 25605972 1 28 theme Anaplastic 76:85 arg1 ALK 104:106 ALK 104:106 ALK 104:106 Anaplastic lymphoma kinase (ALK) is one of the few remaining "orphan" receptor tyrosine kinases (RTKs) in which the ligands are unknown. 25605972 1 28 theme Anaplastic 76:85 arg1 kinase 96:101 Anaplastic lymphoma kinase 76:101 Anaplastic lymphoma kinase (ALK) 76:107 Anaplastic lymphoma kinase (ALK) is one of the few remaining "orphan" receptor tyrosine kinases (RTKs) in which the ligands are unknown. 25605972 1 29 theme " 144:144 arg1 RTKs 173:176 RTKs 173:176 RTKs 173:176 Anaplastic lymphoma kinase (ALK) is one of the few remaining "orphan" receptor tyrosine kinases (RTKs) in which the ligands are unknown. 25605972 1 29 theme " 144:144 arg1 kinases 164:170 the few remaining "orphan" receptor tyrosine kinases 119:170 the few remaining "orphan" receptor tyrosine kinases (RTKs) 119:177 Anaplastic lymphoma kinase (ALK) is one of the few remaining "orphan" receptor tyrosine kinases (RTKs) in which the ligands are unknown. 25605972 0 30 theme activating 14:23 arg1 Heparin 0:6 Heparin 0:6 Heparin 0:6 Heparin is an activating ligand of the orphan receptor tyrosine kinase ALK. 25605972 0 30 theme activating 14:23 arg1 ligand 25:30 an activating ligand 11:30 an activating ligand of the orphan receptor tyrosine kinase ALK 11:73 Heparin is an activating ligand of the orphan receptor tyrosine kinase ALK. 25605972 5 31 theme ALK 546:548 arg1 activation 532:541 Aberrant activation 523:541 Aberrant activation of ALK 523:548 Aberrant activation of ALK occurs in subsets of lung adenocarcinoma, neuroblastoma, and other cancers. 25605972 1 32 theme lymphoma 87:94 arg1 ALK 104:106 ALK 104:106 ALK 104:106 Anaplastic lymphoma kinase (ALK) is one of the few remaining "orphan" receptor tyrosine kinases (RTKs) in which the ligands are unknown. 25605972 1 32 theme lymphoma 87:94 arg1 kinase 96:101 Anaplastic lymphoma kinase 76:101 Anaplastic lymphoma kinase (ALK) 76:107 Anaplastic lymphoma kinase (ALK) is one of the few remaining "orphan" receptor tyrosine kinases (RTKs) in which the ligands are unknown. 25605972 10 33 theme activity 1360:1367 arg1 regulation 1342:1351 the regulation 1338:1351 the regulation of ALK activity in vivo 1338:1375 Thus, heparin and perhaps related glycosaminoglycans function as ligands for ALK, revealing a potential mechanism for the regulation of ALK activity in vivo and suggesting an approach for developing ALK-targeted therapies for cancer. 25605972 1 34 theme receptor 146:153 arg1 RTKs 173:176 RTKs 173:176 RTKs 173:176 Anaplastic lymphoma kinase (ALK) is one of the few remaining "orphan" receptor tyrosine kinases (RTKs) in which the ligands are unknown. 25605972 1 34 theme receptor 146:153 arg1 kinases 164:170 the few remaining "orphan" receptor tyrosine kinases 119:170 the few remaining "orphan" receptor tyrosine kinases (RTKs) 119:177 Anaplastic lymphoma kinase (ALK) is one of the few remaining "orphan" receptor tyrosine kinases (RTKs) in which the ligands are unknown. 25605972 4 35 from resistance 501:510 arg1 cancer 515:520 cancer 515:520 cancer 515:520 Increased activation of RTKs by mutation, genetic amplification, or signals from the stroma contributes to disease progression and acquired drug resistance in cancer. 25605972 7 36 theme short 739:743 arg1 lengths 751:757 short chain lengths 739:757 short chain lengths 739:757 Whereas heparins with short chain lengths bound to ALK in a monovalent manner and did not activate the receptor, longer heparin chains induced ALK dimerization and activation in cultured neuroblastoma cells. 25605972 1 37 from unknown 204:210 arg1 RTKs 173:176 RTKs 173:176 RTKs 173:176 Anaplastic lymphoma kinase (ALK) is one of the few remaining "orphan" receptor tyrosine kinases (RTKs) in which the ligands are unknown. 25605972 1 37 from unknown 204:210 arg1 kinases 164:170 the few remaining "orphan" receptor tyrosine kinases 119:170 the few remaining "orphan" receptor tyrosine kinases (RTKs) 119:177 Anaplastic lymphoma kinase (ALK) is one of the few remaining "orphan" receptor tyrosine kinases (RTKs) in which the ligands are unknown. 25605972 1 37 from unknown 204:210 arg1 one 112:114 one 112:114 one 112:114 Anaplastic lymphoma kinase (ALK) is one of the few remaining "orphan" receptor tyrosine kinases (RTKs) in which the ligands are unknown. 25605972 4 38 theme genetic 398:404 arg1 amplification 406:418 genetic amplification 398:418 genetic amplification 398:418 Increased activation of RTKs by mutation, genetic amplification, or signals from the stroma contributes to disease progression and acquired drug resistance in cancer. 25605972 0 39 dep receptor 46:53 arg1 ALK 71:73 tyrosine kinase ALK 55:73 the orphan receptor tyrosine kinase ALK 35:73 Heparin is an activating ligand of the orphan receptor tyrosine kinase ALK. 25605972 1 40 theme tyrosine 155:162 arg1 RTKs 173:176 RTKs 173:176 RTKs 173:176 Anaplastic lymphoma kinase (ALK) is one of the few remaining "orphan" receptor tyrosine kinases (RTKs) in which the ligands are unknown. 25605972 1 40 theme tyrosine 155:162 arg1 kinases 164:170 the few remaining "orphan" receptor tyrosine kinases 119:170 the few remaining "orphan" receptor tyrosine kinases (RTKs) 119:177 Anaplastic lymphoma kinase (ALK) is one of the few remaining "orphan" receptor tyrosine kinases (RTKs) in which the ligands are unknown. 25605972 8 41 theme sulfation 1005:1013 arg1 patterns 1015:1022 sulfation patterns 1005:1022 sulfation patterns different than heparin 1005:1045 Heparin lacking N- and O-linked sulfate groups or other glycosaminoglycans with sulfation patterns different than heparin failed to activate ALK. 25605972 7 42 theme chain 745:749 arg1 lengths 751:757 short chain lengths 739:757 short chain lengths 739:757 Whereas heparins with short chain lengths bound to ALK in a monovalent manner and did not activate the receptor, longer heparin chains induced ALK dimerization and activation in cultured neuroblastoma cells. 25605972 1 43 theme kinases 164:170 arg1 RTKs 173:176 RTKs 173:176 RTKs 173:176 Anaplastic lymphoma kinase (ALK) is one of the few remaining "orphan" receptor tyrosine kinases (RTKs) in which the ligands are unknown. 25605972 1 43 theme kinases 164:170 arg1 kinases 164:170 the few remaining "orphan" receptor tyrosine kinases 119:170 the few remaining "orphan" receptor tyrosine kinases (RTKs) 119:177 Anaplastic lymphoma kinase (ALK) is one of the few remaining "orphan" receptor tyrosine kinases (RTKs) in which the ligands are unknown. 25605972 1 43 theme kinases 164:170 arg1 one 112:114 one 112:114 one 112:114 Anaplastic lymphoma kinase (ALK) is one of the few remaining "orphan" receptor tyrosine kinases (RTKs) in which the ligands are unknown. 25605972 8 44 link O-linked 948:955 arg1 groups 965:970 O-linked sulfate groups 948:970 O-linked sulfate groups 948:970 Heparin lacking N- and O-linked sulfate groups or other glycosaminoglycans with sulfation patterns different than heparin failed to activate ALK. 25605972 8 45 theme O-linked 948:955 arg1 groups 965:970 O-linked sulfate groups 948:970 O-linked sulfate groups 948:970 Heparin lacking N- and O-linked sulfate groups or other glycosaminoglycans with sulfation patterns different than heparin failed to activate ALK. 25605972 3 46 theme system 348:353 arg1 development 321:331 the development 317:331 the development of the nervous system 317:353 ALK is particularly relevant to the development of the nervous system. 25605972 7 47 with heparins 725:732 arg1 lengths 751:757 short chain lengths 739:757 short chain lengths 739:757 Whereas heparins with short chain lengths bound to ALK in a monovalent manner and did not activate the receptor, longer heparin chains induced ALK dimerization and activation in cultured neuroblastoma cells. 25605972 0 48 theme receptor 46:53 arg1 Heparin 0:6 Heparin 0:6 Heparin 0:6 Heparin is an activating ligand of the orphan receptor tyrosine kinase ALK. 25605972 0 48 theme receptor 46:53 arg1 ligand 25:30 an activating ligand 11:30 an activating ligand of the orphan receptor tyrosine kinase ALK 11:73 Heparin is an activating ligand of the orphan receptor tyrosine kinase ALK. 25605972 6 49 theme extracellular 695:707 arg1 domain 709:714 the ALK extracellular domain 687:714 the ALK extracellular domain 687:714 We found that heparin is a ligand that binds specifically to the ALK extracellular domain. 25605972 4 50 from progression 471:481 arg1 cancer 515:520 cancer 515:520 cancer 515:520 Increased activation of RTKs by mutation, genetic amplification, or signals from the stroma contributes to disease progression and acquired drug resistance in cancer. 25605972 4 51 theme drug 496:499 arg1 resistance 501:510 acquired drug resistance 487:510 acquired drug resistance in cancer 487:520 Increased activation of RTKs by mutation, genetic amplification, or signals from the stroma contributes to disease progression and acquired drug resistance in cancer. 25605972 4 52 theme RTKs 380:383 arg1 activation 366:375 Increased activation 356:375 Increased activation of RTKs by mutation, genetic amplification, or signals from the stroma 356:446 Increased activation of RTKs by mutation, genetic amplification, or signals from the stroma contributes to disease progression and acquired drug resistance in cancer. 25605972 9 53 theme ALK 1215:1217 arg1 activation 1201:1210 heparin-mediated activation 1184:1210 heparin-mediated activation of ALK 1184:1217 Moreover, antibodies that bound to the extracellular domain of ALK interfered with heparin binding and prevented heparin-mediated activation of ALK. 25605972 6 54 theme ALK 691:693 arg1 domain 709:714 the ALK extracellular domain 687:714 the ALK extracellular domain 687:714 We found that heparin is a ligand that binds specifically to the ALK extracellular domain. 25605972 7 55 theme heparin 837:843 arg1 chains 845:850 longer heparin chains 830:850 longer heparin chains 830:850 Whereas heparins with short chain lengths bound to ALK in a monovalent manner and did not activate the receptor, longer heparin chains induced ALK dimerization and activation in cultured neuroblastoma cells. 25605972 4 56 theme acquired 487:494 arg1 resistance 501:510 acquired drug resistance 487:510 acquired drug resistance in cancer 487:520 Increased activation of RTKs by mutation, genetic amplification, or signals from the stroma contributes to disease progression and acquired drug resistance in cancer. 25605972 9 57 theme heparin 1154:1160 arg1 binding 1162:1168 heparin binding 1154:1168 heparin binding 1154:1168 Moreover, antibodies that bound to the extracellular domain of ALK interfered with heparin binding and prevented heparin-mediated activation of ALK. 25605972 9 58 theme ALK 1134:1136 arg1 ALK 1134:1136 ALK 1134:1136 ALK 1134:1136 Moreover, antibodies that bound to the extracellular domain of ALK interfered with heparin binding and prevented heparin-mediated activation of ALK. 25605972 9 58 theme ALK 1134:1136 arg1 domain 1124:1129 the extracellular domain 1106:1129 the extracellular domain of ALK 1106:1136 Moreover, antibodies that bound to the extracellular domain of ALK interfered with heparin binding and prevented heparin-mediated activation of ALK. 25605972 0 59 theme tyrosine 55:62 arg1 ALK 71:73 tyrosine kinase ALK 55:73 the orphan receptor tyrosine kinase ALK 35:73 Heparin is an activating ligand of the orphan receptor tyrosine kinase ALK. 25605972 10 60 theme ALK-targeted 1419:1430 arg1 therapies 1432:1440 ALK-targeted therapies 1419:1440 ALK-targeted therapies for cancer 1419:1451 Thus, heparin and perhaps related glycosaminoglycans function as ligands for ALK, revealing a potential mechanism for the regulation of ALK activity in vivo and suggesting an approach for developing ALK-targeted therapies for cancer. 25605972 7 61 theme longer 830:835 arg1 chains 845:850 longer heparin chains 830:850 longer heparin chains 830:850 Whereas heparins with short chain lengths bound to ALK in a monovalent manner and did not activate the receptor, longer heparin chains induced ALK dimerization and activation in cultured neuroblastoma cells. 25605972 5 62 theme cancers 617:623 arg1 subsets 560:566 subsets 560:566 subsets of lung adenocarcinoma, neuroblastoma, and other cancers 560:623 Aberrant activation of ALK occurs in subsets of lung adenocarcinoma, neuroblastoma, and other cancers. 25605972 0 63 theme orphan 39:44 arg1 receptor 46:53 the orphan receptor tyrosine kinase ALK 35:73 the orphan receptor tyrosine kinase ALK 35:73 Heparin is an activating ligand of the orphan receptor tyrosine kinase ALK. 25605972 9 64 theme extracellular 1110:1122 arg1 ALK 1134:1136 ALK 1134:1136 ALK 1134:1136 Moreover, antibodies that bound to the extracellular domain of ALK interfered with heparin binding and prevented heparin-mediated activation of ALK. 25605972 9 64 theme extracellular 1110:1122 arg1 domain 1124:1129 the extracellular domain 1106:1129 the extracellular domain of ALK 1106:1136 Moreover, antibodies that bound to the extracellular domain of ALK interfered with heparin binding and prevented heparin-mediated activation of ALK. 23624262 3 0 theme glycans 659:665 arg1 library 631:637 a comprehensive LC MS/MS library 606:637 a comprehensive LC MS/MS library of N- and O- linked glycans released from glycoproteins that have been annotated with glycosidic and cross-ring fragmentation ions, retention times, and associated experimental metadata descriptions 606:836 The role of UniCarb-DB, as an archival database, is to provide the glycomics community with open-access to a comprehensive LC MS/MS library of N- and O- linked glycans released from glycoproteins that have been annotated with glycosidic and cross-ring fragmentation ions, retention times, and associated experimental metadata descriptions. 23624262 6 1 theme comparability 1409:1421 arg1 score 1324:1328 A dot product score 1310:1328 A dot product score 1310:1328 A dot product score was calculated for each spectrum in the three sets of data as a measure of the comparability that is necessary for use of such a collection in library-based spectral matching and glycan structural identification. 23624262 6 1 theme comparability 1409:1421 arg1 measure 1394:1400 a measure 1392:1400 a measure of the comparability that is necessary for use of such a collection in library-based spectral matching and glycan structural identification 1392:1540 A dot product score was calculated for each spectrum in the three sets of data as a measure of the comparability that is necessary for use of such a collection in library-based spectral matching and glycan structural identification. 23624262 1 2 theme 2013 230:233 arg1 spectra 209:215 500 tandem mass spectra 193:215 500 tandem mass spectra (as of March 2013) of glycans released from glycoproteins 193:273 The UniCarb-DB database is an emerging public glycomics data repository, containing over 500 tandem mass spectra (as of March 2013) of glycans released from glycoproteins. 23624262 8 3 theme algorithms 1849:1858 arg1 level 1840:1844 the confidence level 1825:1844 the confidence level of algorithms that assign glycan structures to experimental MS/MS spectra 1825:1918 The provision of well-characterized oligosaccharide fragmentation data provides the opportunity to identify determinants of specific glycan structures, and will contribute to the confidence level of algorithms that assign glycan structures to experimental MS/MS spectra. 23624262 5 4 theme graphitized 1181:1191 arg1 chromatography 1207:1220 graphitized carbon-liquid chromatography 1181:1220 graphitized carbon-liquid chromatography (LC) electrospray ionization (ESI) ion trap mass spectrometry in the negative ion mode 1181:1307 In this context, an independent consortium of three laboratories was established to analyze the same 23 commercially available oligosaccharide standards, all by using graphitized carbon-liquid chromatography (LC) electrospray ionization (ESI) ion trap mass spectrometry in the negative ion mode. 23624262 5 4 theme graphitized 1181:1191 arg1 LC 1223:1224 LC 1223:1224 LC 1223:1224 In this context, an independent consortium of three laboratories was established to analyze the same 23 commercially available oligosaccharide standards, all by using graphitized carbon-liquid chromatography (LC) electrospray ionization (ESI) ion trap mass spectrometry in the negative ion mode. 23624262 3 5 theme UniCarb-DB 511:520 arg1 role 503:506 The role 499:506 The role of UniCarb-DB 499:520 The role of UniCarb-DB, as an archival database, is to provide the glycomics community with open-access to a comprehensive LC MS/MS library of N- and O- linked glycans released from glycoproteins that have been annotated with glycosidic and cross-ring fragmentation ions, retention times, and associated experimental metadata descriptions. 23624262 8 6 theme well-characterized 1667:1684 arg1 data 1716:1719 well-characterized oligosaccharide fragmentation data 1667:1719 well-characterized oligosaccharide fragmentation data 1667:1719 The provision of well-characterized oligosaccharide fragmentation data provides the opportunity to identify determinants of specific glycan structures, and will contribute to the confidence level of algorithms that assign glycan structures to experimental MS/MS spectra. 23624262 5 7 from spectrometry 1271:1282 arg1 mode 1304:1307 the negative ion mode 1287:1307 the negative ion mode 1287:1307 In this context, an independent consortium of three laboratories was established to analyze the same 23 commercially available oligosaccharide standards, all by using graphitized carbon-liquid chromatography (LC) electrospray ionization (ESI) ion trap mass spectrometry in the negative ion mode. 23624262 2 8 theme major 278:282 arg1 challenge 284:292 A major challenge 276:292 A major challenge in glycomics research 276:314 A major challenge in glycomics research is to provide and maintain high-quality datasets that will offer the necessary diversity to support the development of accurate bioinformatics tools for data deposition and analysis. 23624262 8 9 theme fragmentation 1702:1714 arg1 data 1716:1719 well-characterized oligosaccharide fragmentation data 1667:1719 well-characterized oligosaccharide fragmentation data 1667:1719 The provision of well-characterized oligosaccharide fragmentation data provides the opportunity to identify determinants of specific glycan structures, and will contribute to the confidence level of algorithms that assign glycan structures to experimental MS/MS spectra. 23624262 6 10 theme dot 1312:1314 arg1 score 1324:1328 A dot product score 1310:1328 A dot product score 1310:1328 A dot product score was calculated for each spectrum in the three sets of data as a measure of the comparability that is necessary for use of such a collection in library-based spectral matching and glycan structural identification. 23624262 6 10 theme dot 1312:1314 arg1 measure 1394:1400 a measure 1392:1400 a measure of the comparability that is necessary for use of such a collection in library-based spectral matching and glycan structural identification 1392:1540 A dot product score was calculated for each spectrum in the three sets of data as a measure of the comparability that is necessary for use of such a collection in library-based spectral matching and glycan structural identification. 23624262 5 11 theme independent 1034:1044 arg1 consortium 1046:1055 an independent consortium 1031:1055 an independent consortium of three laboratories 1031:1077 In this context, an independent consortium of three laboratories was established to analyze the same 23 commercially available oligosaccharide standards, all by using graphitized carbon-liquid chromatography (LC) electrospray ionization (ESI) ion trap mass spectrometry in the negative ion mode. 23624262 3 12 theme archival 529:536 arg1 database 538:545 an archival database 526:545 an archival database 526:545 The role of UniCarb-DB, as an archival database, is to provide the glycomics community with open-access to a comprehensive LC MS/MS library of N- and O- linked glycans released from glycoproteins that have been annotated with glycosidic and cross-ring fragmentation ions, retention times, and associated experimental metadata descriptions. 23624262 7 13 theme levels 1599:1604 arg1 effects 1547:1553 The effects 1543:1553 The effects of charge state, de-isotoping and threshold levels on the quality of the input data 1543:1637 The effects of charge state, de-isotoping and threshold levels on the quality of the input data are shown. 23624262 3 14 theme cross-ring 740:749 arg1 ions 765:768 glycosidic and cross-ring fragmentation ions 725:768 glycosidic and cross-ring fragmentation ions 725:768 The role of UniCarb-DB, as an archival database, is to provide the glycomics community with open-access to a comprehensive LC MS/MS library of N- and O- linked glycans released from glycoproteins that have been annotated with glycosidic and cross-ring fragmentation ions, retention times, and associated experimental metadata descriptions. 23624262 5 15 theme carbon-liquid 1193:1205 arg1 chromatography 1207:1220 graphitized carbon-liquid chromatography 1181:1220 graphitized carbon-liquid chromatography (LC) electrospray ionization (ESI) ion trap mass spectrometry in the negative ion mode 1181:1307 In this context, an independent consortium of three laboratories was established to analyze the same 23 commercially available oligosaccharide standards, all by using graphitized carbon-liquid chromatography (LC) electrospray ionization (ESI) ion trap mass spectrometry in the negative ion mode. 23624262 5 15 theme carbon-liquid 1193:1205 arg1 LC 1223:1224 LC 1223:1224 LC 1223:1224 In this context, an independent consortium of three laboratories was established to analyze the same 23 commercially available oligosaccharide standards, all by using graphitized carbon-liquid chromatography (LC) electrospray ionization (ESI) ion trap mass spectrometry in the negative ion mode. 23624262 1 16 theme mass 204:207 arg1 spectra 209:215 500 tandem mass spectra 193:215 500 tandem mass spectra (as of March 2013) of glycans released from glycoproteins 193:273 The UniCarb-DB database is an emerging public glycomics data repository, containing over 500 tandem mass spectra (as of March 2013) of glycans released from glycoproteins. 23624262 4 17 theme data 873:876 arg1 submission 878:887 the UniCarb-DB data submission 858:887 the UniCarb-DB data submission pipeline 858:896 Here, we introduce the UniCarb-DB data submission pipeline and its practical application to construct a library of LC-MS/MS glycan standards that forms part of this database. 23624262 10 18 dep Editors 2034:2040 arg1 Editors 2034:2040 Guest Editors 2028:2040 Guest Editors: Martin Eisenacher and Christian Stephan. 2028:2082 Guest Editors: Martin Eisenacher and Christian Stephan. 23624262 10 18 dep Editors 2034:2040 arg1 Eisenacher 2050:2059 Eisenacher 2050:2059 Eisenacher 2050:2059 Guest Editors: Martin Eisenacher and Christian Stephan. 23624262 10 18 dep Editors 2034:2040 arg1 Stephan 2075:2081 Stephan 2075:2081 Stephan 2075:2081 Guest Editors: Martin Eisenacher and Christian Stephan. 23624262 3 19 theme glycosidic 725:734 arg1 ions 765:768 glycosidic and cross-ring fragmentation ions 725:768 glycosidic and cross-ring fragmentation ions 725:768 The role of UniCarb-DB, as an archival database, is to provide the glycomics community with open-access to a comprehensive LC MS/MS library of N- and O- linked glycans released from glycoproteins that have been annotated with glycosidic and cross-ring fragmentation ions, retention times, and associated experimental metadata descriptions. 23624262 1 20 gly glycoproteins 261:273 arg1 glycoproteins 261:273 glycoproteins 261:273 glycoproteins 261:273 The UniCarb-DB database is an emerging public glycomics data repository, containing over 500 tandem mass spectra (as of March 2013) of glycans released from glycoproteins. 23624262 1 21 theme UniCarb-DB 108:117 arg1 database 119:126 The UniCarb-DB database 104:126 The UniCarb-DB database 104:126 The UniCarb-DB database is an emerging public glycomics data repository, containing over 500 tandem mass spectra (as of March 2013) of glycans released from glycoproteins. 23624262 1 21 theme UniCarb-DB 108:117 arg1 repository 165:174 an emerging public glycomics data repository 131:174 an emerging public glycomics data repository 131:174 The UniCarb-DB database is an emerging public glycomics data repository, containing over 500 tandem mass spectra (as of March 2013) of glycans released from glycoproteins. 23624262 8 22 theme experimental 1893:1904 arg1 spectra 1912:1918 experimental MS/MS spectra 1893:1918 experimental MS/MS spectra 1893:1918 The provision of well-characterized oligosaccharide fragmentation data provides the opportunity to identify determinants of specific glycan structures, and will contribute to the confidence level of algorithms that assign glycan structures to experimental MS/MS spectra. 23624262 9 23 theme Issue 1955:1959 arg1 part 1937:1940 part 1937:1940 part of a Special Issue entitled 1937:1968 This article is part of a Special Issue entitled: Computational Proteomics in the Post-Identification Era. 23624262 5 24 theme mass 1266:1269 arg1 spectrometry 1271:1282 graphitized carbon-liquid chromatography (LC) electrospray ionization (ESI) ion trap mass spectrometry 1181:1282 graphitized carbon-liquid chromatography (LC) electrospray ionization (ESI) ion trap mass spectrometry in the negative ion mode 1181:1307 In this context, an independent consortium of three laboratories was established to analyze the same 23 commercially available oligosaccharide standards, all by using graphitized carbon-liquid chromatography (LC) electrospray ionization (ESI) ion trap mass spectrometry in the negative ion mode. 23624262 3 25 theme retention 771:779 arg1 times 781:785 retention times 771:785 retention times 771:785 The role of UniCarb-DB, as an archival database, is to provide the glycomics community with open-access to a comprehensive LC MS/MS library of N- and O- linked glycans released from glycoproteins that have been annotated with glycosidic and cross-ring fragmentation ions, retention times, and associated experimental metadata descriptions. 23624262 3 26 theme metadata 816:823 arg1 descriptions 825:836 associated experimental metadata descriptions 792:836 associated experimental metadata descriptions 792:836 The role of UniCarb-DB, as an archival database, is to provide the glycomics community with open-access to a comprehensive LC MS/MS library of N- and O- linked glycans released from glycoproteins that have been annotated with glycosidic and cross-ring fragmentation ions, retention times, and associated experimental metadata descriptions. 23624262 7 27 theme charge 1558:1563 arg1 state 1565:1569 charge state 1558:1569 charge state 1558:1569 The effects of charge state, de-isotoping and threshold levels on the quality of the input data are shown. 23624262 4 28 theme LC-MS/MS 954:961 arg1 standards 970:978 LC-MS/MS glycan standards 954:978 LC-MS/MS glycan standards that forms part of this database 954:1011 Here, we introduce the UniCarb-DB data submission pipeline and its practical application to construct a library of LC-MS/MS glycan standards that forms part of this database. 23624262 1 29 dep 2013 230:233 arg1 as 218:219 as 218:219 as 218:219 The UniCarb-DB database is an emerging public glycomics data repository, containing over 500 tandem mass spectra (as of March 2013) of glycans released from glycoproteins. 23624262 3 30 with community 576:584 arg1 open-access 591:601 open-access 591:601 open-access 591:601 The role of UniCarb-DB, as an archival database, is to provide the glycomics community with open-access to a comprehensive LC MS/MS library of N- and O- linked glycans released from glycoproteins that have been annotated with glycosidic and cross-ring fragmentation ions, retention times, and associated experimental metadata descriptions. 23624262 6 31 from spectrum 1354:1361 arg1 data 1384:1387 data 1384:1387 data 1384:1387 A dot product score was calculated for each spectrum in the three sets of data as a measure of the comparability that is necessary for use of such a collection in library-based spectral matching and glycan structural identification. 23624262 6 31 from spectrum 1354:1361 arg1 sets 1376:1379 the three sets 1366:1379 the three sets of data 1366:1387 A dot product score was calculated for each spectrum in the three sets of data as a measure of the comparability that is necessary for use of such a collection in library-based spectral matching and glycan structural identification. 23624262 6 32 theme structural 1516:1525 arg1 identification 1527:1540 glycan structural identification 1509:1540 glycan structural identification 1509:1540 A dot product score was calculated for each spectrum in the three sets of data as a measure of the comparability that is necessary for use of such a collection in library-based spectral matching and glycan structural identification. 23624262 1 33 theme emerging 134:141 arg1 database 119:126 The UniCarb-DB database 104:126 The UniCarb-DB database 104:126 The UniCarb-DB database is an emerging public glycomics data repository, containing over 500 tandem mass spectra (as of March 2013) of glycans released from glycoproteins. 23624262 1 33 theme emerging 134:141 arg1 repository 165:174 an emerging public glycomics data repository 131:174 an emerging public glycomics data repository 131:174 The UniCarb-DB database is an emerging public glycomics data repository, containing over 500 tandem mass spectra (as of March 2013) of glycans released from glycoproteins. 23624262 2 34 theme data 469:472 arg1 deposition 474:483 data deposition 469:483 data deposition 469:483 A major challenge in glycomics research is to provide and maintain high-quality datasets that will offer the necessary diversity to support the development of accurate bioinformatics tools for data deposition and analysis. 23624262 5 35 theme ESI 1252:1254 arg1 spectrometry 1271:1282 graphitized carbon-liquid chromatography (LC) electrospray ionization (ESI) ion trap mass spectrometry 1181:1282 graphitized carbon-liquid chromatography (LC) electrospray ionization (ESI) ion trap mass spectrometry in the negative ion mode 1181:1307 In this context, an independent consortium of three laboratories was established to analyze the same 23 commercially available oligosaccharide standards, all by using graphitized carbon-liquid chromatography (LC) electrospray ionization (ESI) ion trap mass spectrometry in the negative ion mode. 23624262 3 36 theme associated 792:801 arg1 descriptions 825:836 associated experimental metadata descriptions 792:836 associated experimental metadata descriptions 792:836 The role of UniCarb-DB, as an archival database, is to provide the glycomics community with open-access to a comprehensive LC MS/MS library of N- and O- linked glycans released from glycoproteins that have been annotated with glycosidic and cross-ring fragmentation ions, retention times, and associated experimental metadata descriptions. 23624262 0 37 theme global 62:67 arg1 repository 92:101 a global glycan reference MS/MS repository 60:101 a global glycan reference MS/MS repository 60:101 Validation of the curation pipeline of UniCarb-DB: building a global glycan reference MS/MS repository. 23624262 5 38 theme same 1110:1113 arg1 standards 1157:1165 the same 23 commercially available oligosaccharide standards 1106:1165 the same 23 commercially available oligosaccharide standards 1106:1165 In this context, an independent consortium of three laboratories was established to analyze the same 23 commercially available oligosaccharide standards, all by using graphitized carbon-liquid chromatography (LC) electrospray ionization (ESI) ion trap mass spectrometry in the negative ion mode. 23624262 1 39 theme glycomics 150:158 arg1 database 119:126 The UniCarb-DB database 104:126 The UniCarb-DB database 104:126 The UniCarb-DB database is an emerging public glycomics data repository, containing over 500 tandem mass spectra (as of March 2013) of glycans released from glycoproteins. 23624262 1 39 theme glycomics 150:158 arg1 repository 165:174 an emerging public glycomics data repository 131:174 an emerging public glycomics data repository 131:174 The UniCarb-DB database is an emerging public glycomics data repository, containing over 500 tandem mass spectra (as of March 2013) of glycans released from glycoproteins. 23624262 2 40 from challenge 284:292 arg1 research 307:314 glycomics research 297:314 glycomics research 297:314 A major challenge in glycomics research is to provide and maintain high-quality datasets that will offer the necessary diversity to support the development of accurate bioinformatics tools for data deposition and analysis. 23624262 5 41 theme ion 1257:1259 arg1 spectrometry 1271:1282 graphitized carbon-liquid chromatography (LC) electrospray ionization (ESI) ion trap mass spectrometry 1181:1282 graphitized carbon-liquid chromatography (LC) electrospray ionization (ESI) ion trap mass spectrometry in the negative ion mode 1181:1307 In this context, an independent consortium of three laboratories was established to analyze the same 23 commercially available oligosaccharide standards, all by using graphitized carbon-liquid chromatography (LC) electrospray ionization (ESI) ion trap mass spectrometry in the negative ion mode. 23624262 10 42 theme Guest 2028:2032 arg1 Editors 2034:2040 Guest Editors 2028:2040 Guest Editors: Martin Eisenacher and Christian Stephan. 2028:2082 Guest Editors: Martin Eisenacher and Christian Stephan. 23624262 10 42 theme Guest 2028:2032 arg1 Eisenacher 2050:2059 Eisenacher 2050:2059 Eisenacher 2050:2059 Guest Editors: Martin Eisenacher and Christian Stephan. 23624262 10 42 theme Guest 2028:2032 arg1 Stephan 2075:2081 Stephan 2075:2081 Stephan 2075:2081 Guest Editors: Martin Eisenacher and Christian Stephan. 23624262 0 43 theme reference 76:84 arg1 repository 92:101 a global glycan reference MS/MS repository 60:101 a global glycan reference MS/MS repository 60:101 Validation of the curation pipeline of UniCarb-DB: building a global glycan reference MS/MS repository. 23624262 5 44 theme laboratories 1066:1077 arg1 consortium 1046:1055 an independent consortium 1031:1055 an independent consortium of three laboratories 1031:1077 In this context, an independent consortium of three laboratories was established to analyze the same 23 commercially available oligosaccharide standards, all by using graphitized carbon-liquid chromatography (LC) electrospray ionization (ESI) ion trap mass spectrometry in the negative ion mode. 23624262 7 45 theme data 1634:1637 arg1 quality 1613:1619 the quality 1609:1619 the quality of the input data 1609:1637 The effects of charge state, de-isotoping and threshold levels on the quality of the input data are shown. 23624262 9 46 from Proteomics 1985:1994 arg1 Era 2023:2025 the Post-Identification Era 1999:2025 the Post-Identification Era 1999:2025 This article is part of a Special Issue entitled: Computational Proteomics in the Post-Identification Era. 23624262 4 47 theme database 1004:1011 arg1 part 991:994 part 991:994 part of this database 991:1011 Here, we introduce the UniCarb-DB data submission pipeline and its practical application to construct a library of LC-MS/MS glycan standards that forms part of this database. 23624262 1 48 theme glycans 239:245 arg1 spectra 209:215 500 tandem mass spectra 193:215 500 tandem mass spectra (as of March 2013) of glycans released from glycoproteins 193:273 The UniCarb-DB database is an emerging public glycomics data repository, containing over 500 tandem mass spectra (as of March 2013) of glycans released from glycoproteins. 23624262 8 49 theme confidence 1829:1838 arg1 level 1840:1844 the confidence level 1825:1844 the confidence level of algorithms that assign glycan structures to experimental MS/MS spectra 1825:1918 The provision of well-characterized oligosaccharide fragmentation data provides the opportunity to identify determinants of specific glycan structures, and will contribute to the confidence level of algorithms that assign glycan structures to experimental MS/MS spectra. 23624262 3 50 gly glycoproteins 681:693 arg1 glycoproteins 681:693 glycoproteins 681:693 glycoproteins that have been annotated with glycosidic and cross-ring fragmentation ions, retention times, and associated experimental metadata descriptions 681:836 The role of UniCarb-DB, as an archival database, is to provide the glycomics community with open-access to a comprehensive LC MS/MS library of N- and O- linked glycans released from glycoproteins that have been annotated with glycosidic and cross-ring fragmentation ions, retention times, and associated experimental metadata descriptions. 23624262 5 51 theme negative 1291:1298 arg1 mode 1304:1307 the negative ion mode 1287:1307 the negative ion mode 1287:1307 In this context, an independent consortium of three laboratories was established to analyze the same 23 commercially available oligosaccharide standards, all by using graphitized carbon-liquid chromatography (LC) electrospray ionization (ESI) ion trap mass spectrometry in the negative ion mode. 23624262 3 52 dep linked 652:657 arg1 O- 649:650 O- 649:650 O- 649:650 The role of UniCarb-DB, as an archival database, is to provide the glycomics community with open-access to a comprehensive LC MS/MS library of N- and O- linked glycans released from glycoproteins that have been annotated with glycosidic and cross-ring fragmentation ions, retention times, and associated experimental metadata descriptions. 23624262 6 53 from collection 1459:1468 arg1 spectral 1487:1494 library-based spectral 1473:1494 library-based spectral matching 1473:1503 A dot product score was calculated for each spectrum in the three sets of data as a measure of the comparability that is necessary for use of such a collection in library-based spectral matching and glycan structural identification. 23624262 2 54 theme tools 459:463 arg1 development 420:430 the development 416:430 the development of accurate bioinformatics tools for data deposition and analysis 416:496 A major challenge in glycomics research is to provide and maintain high-quality datasets that will offer the necessary diversity to support the development of accurate bioinformatics tools for data deposition and analysis. 23624262 3 55 theme LC 622:623 arg1 library 631:637 a comprehensive LC MS/MS library 606:637 a comprehensive LC MS/MS library of N- and O- linked glycans released from glycoproteins that have been annotated with glycosidic and cross-ring fragmentation ions, retention times, and associated experimental metadata descriptions 606:836 The role of UniCarb-DB, as an archival database, is to provide the glycomics community with open-access to a comprehensive LC MS/MS library of N- and O- linked glycans released from glycoproteins that have been annotated with glycosidic and cross-ring fragmentation ions, retention times, and associated experimental metadata descriptions. 23624262 0 56 theme pipeline 27:34 arg1 Validation 0:9 Validation 0:9 Validation of the curation pipeline of UniCarb-DB: 0:49 Validation of the curation pipeline of UniCarb-DB: building a global glycan reference MS/MS repository. 23624262 2 57 theme accurate 435:442 arg1 tools 459:463 accurate bioinformatics tools 435:463 accurate bioinformatics tools for data deposition and analysis 435:496 A major challenge in glycomics research is to provide and maintain high-quality datasets that will offer the necessary diversity to support the development of accurate bioinformatics tools for data deposition and analysis. 23624262 0 58 theme UniCarb-DB 39:48 arg1 pipeline 27:34 the curation pipeline 14:34 the curation pipeline of UniCarb-DB 14:48 Validation of the curation pipeline of UniCarb-DB: building a global glycan reference MS/MS repository. 23624262 5 59 theme oligosaccharide 1141:1155 arg1 standards 1157:1165 the same 23 commercially available oligosaccharide standards 1106:1165 the same 23 commercially available oligosaccharide standards 1106:1165 In this context, an independent consortium of three laboratories was established to analyze the same 23 commercially available oligosaccharide standards, all by using graphitized carbon-liquid chromatography (LC) electrospray ionization (ESI) ion trap mass spectrometry in the negative ion mode. 23624262 7 60 from effects 1547:1553 arg1 quality 1613:1619 the quality 1609:1619 the quality of the input data 1609:1637 The effects of charge state, de-isotoping and threshold levels on the quality of the input data are shown. 23624262 6 61 from use 1445:1447 arg1 spectral 1487:1494 library-based spectral 1473:1494 library-based spectral matching 1473:1503 A dot product score was calculated for each spectrum in the three sets of data as a measure of the comparability that is necessary for use of such a collection in library-based spectral matching and glycan structural identification. 23624262 3 62 theme N- 642:643 arg1 library 631:637 a comprehensive LC MS/MS library 606:637 a comprehensive LC MS/MS library of N- and O- linked glycans released from glycoproteins that have been annotated with glycosidic and cross-ring fragmentation ions, retention times, and associated experimental metadata descriptions 606:836 The role of UniCarb-DB, as an archival database, is to provide the glycomics community with open-access to a comprehensive LC MS/MS library of N- and O- linked glycans released from glycoproteins that have been annotated with glycosidic and cross-ring fragmentation ions, retention times, and associated experimental metadata descriptions. 23624262 2 63 theme glycomics 297:305 arg1 research 307:314 glycomics research 297:314 glycomics research 297:314 A major challenge in glycomics research is to provide and maintain high-quality datasets that will offer the necessary diversity to support the development of accurate bioinformatics tools for data deposition and analysis. 23624262 8 64 theme glycan 1783:1788 arg1 structures 1790:1799 specific glycan structures 1774:1799 specific glycan structures 1774:1799 The provision of well-characterized oligosaccharide fragmentation data provides the opportunity to identify determinants of specific glycan structures, and will contribute to the confidence level of algorithms that assign glycan structures to experimental MS/MS spectra. 23624262 5 65 theme electrospray 1227:1238 arg1 spectrometry 1271:1282 graphitized carbon-liquid chromatography (LC) electrospray ionization (ESI) ion trap mass spectrometry 1181:1282 graphitized carbon-liquid chromatography (LC) electrospray ionization (ESI) ion trap mass spectrometry in the negative ion mode 1181:1307 In this context, an independent consortium of three laboratories was established to analyze the same 23 commercially available oligosaccharide standards, all by using graphitized carbon-liquid chromatography (LC) electrospray ionization (ESI) ion trap mass spectrometry in the negative ion mode. 23624262 4 66 theme standards 970:978 arg1 library 943:949 a library 941:949 a library of LC-MS/MS glycan standards that forms part of this database 941:1011 Here, we introduce the UniCarb-DB data submission pipeline and its practical application to construct a library of LC-MS/MS glycan standards that forms part of this database. 23624262 1 67 theme March 224:228 arg1 2013 230:233 March 2013 224:233 March 2013 224:233 The UniCarb-DB database is an emerging public glycomics data repository, containing over 500 tandem mass spectra (as of March 2013) of glycans released from glycoproteins. 23624262 3 68 attach released 667:674 arg1 glycoproteins 681:693 glycoproteins 681:693 glycoproteins that have been annotated with glycosidic and cross-ring fragmentation ions, retention times, and associated experimental metadata descriptions 681:836 The role of UniCarb-DB, as an archival database, is to provide the glycomics community with open-access to a comprehensive LC MS/MS library of N- and O- linked glycans released from glycoproteins that have been annotated with glycosidic and cross-ring fragmentation ions, retention times, and associated experimental metadata descriptions. 23624262 3 68 attach released 667:674 arg2 glycans 659:665 O- linked glycans 649:665 O- linked glycans released from glycoproteins that have been annotated with glycosidic and cross-ring fragmentation ions, retention times, and associated experimental metadata descriptions 649:836 The role of UniCarb-DB, as an archival database, is to provide the glycomics community with open-access to a comprehensive LC MS/MS library of N- and O- linked glycans released from glycoproteins that have been annotated with glycosidic and cross-ring fragmentation ions, retention times, and associated experimental metadata descriptions. 23624262 1 69 attach released 247:254 arg2 glycans 239:245 glycans 239:245 glycans released from glycoproteins 239:273 The UniCarb-DB database is an emerging public glycomics data repository, containing over 500 tandem mass spectra (as of March 2013) of glycans released from glycoproteins. 23624262 1 69 attach released 247:254 arg1 glycoproteins 261:273 glycoproteins 261:273 glycoproteins 261:273 The UniCarb-DB database is an emerging public glycomics data repository, containing over 500 tandem mass spectra (as of March 2013) of glycans released from glycoproteins. 23624262 8 70 theme specific 1774:1781 arg1 structures 1790:1799 specific glycan structures 1774:1799 specific glycan structures 1774:1799 The provision of well-characterized oligosaccharide fragmentation data provides the opportunity to identify determinants of specific glycan structures, and will contribute to the confidence level of algorithms that assign glycan structures to experimental MS/MS spectra. 23624262 5 71 theme chromatography 1207:1220 arg1 spectrometry 1271:1282 graphitized carbon-liquid chromatography (LC) electrospray ionization (ESI) ion trap mass spectrometry 1181:1282 graphitized carbon-liquid chromatography (LC) electrospray ionization (ESI) ion trap mass spectrometry in the negative ion mode 1181:1307 In this context, an independent consortium of three laboratories was established to analyze the same 23 commercially available oligosaccharide standards, all by using graphitized carbon-liquid chromatography (LC) electrospray ionization (ESI) ion trap mass spectrometry in the negative ion mode. 23624262 8 72 theme glycan 1872:1877 arg1 structures 1879:1888 glycan structures 1872:1888 glycan structures 1872:1888 The provision of well-characterized oligosaccharide fragmentation data provides the opportunity to identify determinants of specific glycan structures, and will contribute to the confidence level of algorithms that assign glycan structures to experimental MS/MS spectra. 23624262 1 73 theme data 160:163 arg1 database 119:126 The UniCarb-DB database 104:126 The UniCarb-DB database 104:126 The UniCarb-DB database is an emerging public glycomics data repository, containing over 500 tandem mass spectra (as of March 2013) of glycans released from glycoproteins. 23624262 1 73 theme data 160:163 arg1 repository 165:174 an emerging public glycomics data repository 131:174 an emerging public glycomics data repository 131:174 The UniCarb-DB database is an emerging public glycomics data repository, containing over 500 tandem mass spectra (as of March 2013) of glycans released from glycoproteins. 23624262 6 74 theme library-based 1473:1485 arg1 spectral 1487:1494 library-based spectral 1473:1494 library-based spectral matching 1473:1503 A dot product score was calculated for each spectrum in the three sets of data as a measure of the comparability that is necessary for use of such a collection in library-based spectral matching and glycan structural identification. 23624262 6 75 theme product 1316:1322 arg1 score 1324:1328 A dot product score 1310:1328 A dot product score 1310:1328 A dot product score was calculated for each spectrum in the three sets of data as a measure of the comparability that is necessary for use of such a collection in library-based spectral matching and glycan structural identification. 23624262 6 75 theme product 1316:1322 arg1 measure 1394:1400 a measure 1392:1400 a measure of the comparability that is necessary for use of such a collection in library-based spectral matching and glycan structural identification 1392:1540 A dot product score was calculated for each spectrum in the three sets of data as a measure of the comparability that is necessary for use of such a collection in library-based spectral matching and glycan structural identification. 23624262 6 76 theme collection 1459:1468 arg1 use 1445:1447 use 1445:1447 use of such a collection in library-based spectral matching and glycan structural identification 1445:1540 A dot product score was calculated for each spectrum in the three sets of data as a measure of the comparability that is necessary for use of such a collection in library-based spectral matching and glycan structural identification. 23624262 7 77 theme threshold 1589:1597 arg1 levels 1599:1604 threshold levels 1589:1604 threshold levels 1589:1604 The effects of charge state, de-isotoping and threshold levels on the quality of the input data are shown. 23624262 6 78 from identification 1527:1540 arg1 spectral 1487:1494 library-based spectral 1473:1494 library-based spectral matching 1473:1503 A dot product score was calculated for each spectrum in the three sets of data as a measure of the comparability that is necessary for use of such a collection in library-based spectral matching and glycan structural identification. 23624262 3 79 link linked 652:657 arg1 glycans 659:665 O- linked glycans 649:665 O- linked glycans released from glycoproteins that have been annotated with glycosidic and cross-ring fragmentation ions, retention times, and associated experimental metadata descriptions 649:836 The role of UniCarb-DB, as an archival database, is to provide the glycomics community with open-access to a comprehensive LC MS/MS library of N- and O- linked glycans released from glycoproteins that have been annotated with glycosidic and cross-ring fragmentation ions, retention times, and associated experimental metadata descriptions. 23624262 8 80 theme data 1716:1719 arg1 provision 1654:1662 The provision 1650:1662 The provision of well-characterized oligosaccharide fragmentation data 1650:1719 The provision of well-characterized oligosaccharide fragmentation data provides the opportunity to identify determinants of specific glycan structures, and will contribute to the confidence level of algorithms that assign glycan structures to experimental MS/MS spectra. 23624262 1 81 theme tandem 197:202 arg1 spectra 209:215 500 tandem mass spectra 193:215 500 tandem mass spectra (as of March 2013) of glycans released from glycoproteins 193:273 The UniCarb-DB database is an emerging public glycomics data repository, containing over 500 tandem mass spectra (as of March 2013) of glycans released from glycoproteins. 23624262 7 82 theme de-isotoping 1572:1583 arg1 effects 1547:1553 The effects 1543:1553 The effects of charge state, de-isotoping and threshold levels on the quality of the input data 1543:1637 The effects of charge state, de-isotoping and threshold levels on the quality of the input data are shown. 23624262 4 83 theme practical 906:914 arg1 application 916:926 its practical application 902:926 its practical application to construct a library of LC-MS/MS glycan standards that forms part of this database 902:1011 Here, we introduce the UniCarb-DB data submission pipeline and its practical application to construct a library of LC-MS/MS glycan standards that forms part of this database. 23624262 3 84 theme fragmentation 751:763 arg1 ions 765:768 glycosidic and cross-ring fragmentation ions 725:768 glycosidic and cross-ring fragmentation ions 725:768 The role of UniCarb-DB, as an archival database, is to provide the glycomics community with open-access to a comprehensive LC MS/MS library of N- and O- linked glycans released from glycoproteins that have been annotated with glycosidic and cross-ring fragmentation ions, retention times, and associated experimental metadata descriptions. 23624262 7 85 theme state 1565:1569 arg1 effects 1547:1553 The effects 1543:1553 The effects of charge state, de-isotoping and threshold levels on the quality of the input data 1543:1637 The effects of charge state, de-isotoping and threshold levels on the quality of the input data are shown. 23624262 4 86 theme UniCarb-DB 862:871 arg1 submission 878:887 the UniCarb-DB data submission 858:887 the UniCarb-DB data submission pipeline 858:896 Here, we introduce the UniCarb-DB data submission pipeline and its practical application to construct a library of LC-MS/MS glycan standards that forms part of this database. 23624262 9 87 theme Special 1947:1953 arg1 Issue 1955:1959 a Special Issue 1945:1959 a Special Issue entitled 1945:1968 This article is part of a Special Issue entitled: Computational Proteomics in the Post-Identification Era. 23624262 5 88 theme trap 1261:1264 arg1 spectrometry 1271:1282 graphitized carbon-liquid chromatography (LC) electrospray ionization (ESI) ion trap mass spectrometry 1181:1282 graphitized carbon-liquid chromatography (LC) electrospray ionization (ESI) ion trap mass spectrometry in the negative ion mode 1181:1307 In this context, an independent consortium of three laboratories was established to analyze the same 23 commercially available oligosaccharide standards, all by using graphitized carbon-liquid chromatography (LC) electrospray ionization (ESI) ion trap mass spectrometry in the negative ion mode. 23624262 4 89 theme submission 878:887 arg1 pipeline 889:896 the UniCarb-DB data submission pipeline 858:896 the UniCarb-DB data submission pipeline 858:896 Here, we introduce the UniCarb-DB data submission pipeline and its practical application to construct a library of LC-MS/MS glycan standards that forms part of this database. 23624262 8 90 theme oligosaccharide 1686:1700 arg1 data 1716:1719 well-characterized oligosaccharide fragmentation data 1667:1719 well-characterized oligosaccharide fragmentation data 1667:1719 The provision of well-characterized oligosaccharide fragmentation data provides the opportunity to identify determinants of specific glycan structures, and will contribute to the confidence level of algorithms that assign glycan structures to experimental MS/MS spectra. 23624262 3 91 theme glycomics 566:574 arg1 community 576:584 the glycomics community 562:584 the glycomics community with open-access to a comprehensive LC MS/MS library of N- and O- linked glycans released from glycoproteins that have been annotated with glycosidic and cross-ring fragmentation ions, retention times, and associated experimental metadata descriptions 562:836 The role of UniCarb-DB, as an archival database, is to provide the glycomics community with open-access to a comprehensive LC MS/MS library of N- and O- linked glycans released from glycoproteins that have been annotated with glycosidic and cross-ring fragmentation ions, retention times, and associated experimental metadata descriptions. 23624262 6 92 theme identification 1527:1540 arg1 use 1445:1447 use 1445:1447 use of such a collection in library-based spectral matching and glycan structural identification 1445:1540 A dot product score was calculated for each spectrum in the three sets of data as a measure of the comparability that is necessary for use of such a collection in library-based spectral matching and glycan structural identification. 23624262 9 93 theme Computational 1971:1983 arg1 Proteomics 1985:1994 Computational Proteomics 1971:1994 Computational Proteomics in the Post-Identification Era 1971:2025 This article is part of a Special Issue entitled: Computational Proteomics in the Post-Identification Era. 23624262 0 94 theme glycan 69:74 arg1 repository 92:101 a global glycan reference MS/MS repository 60:101 a global glycan reference MS/MS repository 60:101 Validation of the curation pipeline of UniCarb-DB: building a global glycan reference MS/MS repository. 23624262 6 95 theme glycan 1509:1514 arg1 identification 1527:1540 glycan structural identification 1509:1540 glycan structural identification 1509:1540 A dot product score was calculated for each spectrum in the three sets of data as a measure of the comparability that is necessary for use of such a collection in library-based spectral matching and glycan structural identification. 23624262 1 96 theme public 143:148 arg1 database 119:126 The UniCarb-DB database 104:126 The UniCarb-DB database 104:126 The UniCarb-DB database is an emerging public glycomics data repository, containing over 500 tandem mass spectra (as of March 2013) of glycans released from glycoproteins. 23624262 1 96 theme public 143:148 arg1 repository 165:174 an emerging public glycomics data repository 131:174 an emerging public glycomics data repository 131:174 The UniCarb-DB database is an emerging public glycomics data repository, containing over 500 tandem mass spectra (as of March 2013) of glycans released from glycoproteins. 23624262 4 97 theme glycan 963:968 arg1 standards 970:978 LC-MS/MS glycan standards 954:978 LC-MS/MS glycan standards that forms part of this database 954:1011 Here, we introduce the UniCarb-DB data submission pipeline and its practical application to construct a library of LC-MS/MS glycan standards that forms part of this database. 23624262 3 98 theme experimental 803:814 arg1 descriptions 825:836 associated experimental metadata descriptions 792:836 associated experimental metadata descriptions 792:836 The role of UniCarb-DB, as an archival database, is to provide the glycomics community with open-access to a comprehensive LC MS/MS library of N- and O- linked glycans released from glycoproteins that have been annotated with glycosidic and cross-ring fragmentation ions, retention times, and associated experimental metadata descriptions. 23624262 0 99 theme MS/MS 86:90 arg1 repository 92:101 a global glycan reference MS/MS repository 60:101 a global glycan reference MS/MS repository 60:101 Validation of the curation pipeline of UniCarb-DB: building a global glycan reference MS/MS repository. 23624262 8 100 theme structures 1790:1799 arg1 determinants 1758:1769 determinants 1758:1769 determinants of specific glycan structures 1758:1799 The provision of well-characterized oligosaccharide fragmentation data provides the opportunity to identify determinants of specific glycan structures, and will contribute to the confidence level of algorithms that assign glycan structures to experimental MS/MS spectra. 23624262 6 101 from spectral 1487:1494 arg1 use 1445:1447 use 1445:1447 use of such a collection in library-based spectral matching and glycan structural identification 1445:1540 A dot product score was calculated for each spectrum in the three sets of data as a measure of the comparability that is necessary for use of such a collection in library-based spectral matching and glycan structural identification. 23624262 9 102 theme Post-Identification 2003:2021 arg1 Era 2023:2025 the Post-Identification Era 1999:2025 the Post-Identification Era 1999:2025 This article is part of a Special Issue entitled: Computational Proteomics in the Post-Identification Era. 23624262 2 103 theme high-quality 343:354 arg1 datasets 356:363 high-quality datasets 343:363 high-quality datasets that will offer the necessary diversity to support the development of accurate bioinformatics tools for data deposition and analysis 343:496 A major challenge in glycomics research is to provide and maintain high-quality datasets that will offer the necessary diversity to support the development of accurate bioinformatics tools for data deposition and analysis. 23624262 0 104 theme curation 18:25 arg1 pipeline 27:34 the curation pipeline 14:34 the curation pipeline of UniCarb-DB 14:48 Validation of the curation pipeline of UniCarb-DB: building a global glycan reference MS/MS repository. 23624262 7 105 theme input 1628:1632 arg1 data 1634:1637 the input data 1624:1637 the input data 1624:1637 The effects of charge state, de-isotoping and threshold levels on the quality of the input data are shown. 23624262 3 106 theme comprehensive 608:620 arg1 library 631:637 a comprehensive LC MS/MS library 606:637 a comprehensive LC MS/MS library of N- and O- linked glycans released from glycoproteins that have been annotated with glycosidic and cross-ring fragmentation ions, retention times, and associated experimental metadata descriptions 606:836 The role of UniCarb-DB, as an archival database, is to provide the glycomics community with open-access to a comprehensive LC MS/MS library of N- and O- linked glycans released from glycoproteins that have been annotated with glycosidic and cross-ring fragmentation ions, retention times, and associated experimental metadata descriptions. 23624262 5 107 theme ion 1300:1302 arg1 mode 1304:1307 the negative ion mode 1287:1307 the negative ion mode 1287:1307 In this context, an independent consortium of three laboratories was established to analyze the same 23 commercially available oligosaccharide standards, all by using graphitized carbon-liquid chromatography (LC) electrospray ionization (ESI) ion trap mass spectrometry in the negative ion mode. 23624262 2 108 theme necessary 385:393 arg1 diversity 395:403 the necessary diversity 381:403 the necessary diversity to support the development of accurate bioinformatics tools for data deposition and analysis 381:496 A major challenge in glycomics research is to provide and maintain high-quality datasets that will offer the necessary diversity to support the development of accurate bioinformatics tools for data deposition and analysis. 23624262 6 109 theme data 1384:1387 arg1 data 1384:1387 data 1384:1387 data 1384:1387 A dot product score was calculated for each spectrum in the three sets of data as a measure of the comparability that is necessary for use of such a collection in library-based spectral matching and glycan structural identification. 23624262 6 109 theme data 1384:1387 arg1 sets 1376:1379 the three sets 1366:1379 the three sets of data 1366:1387 A dot product score was calculated for each spectrum in the three sets of data as a measure of the comparability that is necessary for use of such a collection in library-based spectral matching and glycan structural identification. 23624262 8 110 theme MS/MS 1906:1910 arg1 spectra 1912:1918 experimental MS/MS spectra 1893:1918 experimental MS/MS spectra 1893:1918 The provision of well-characterized oligosaccharide fragmentation data provides the opportunity to identify determinants of specific glycan structures, and will contribute to the confidence level of algorithms that assign glycan structures to experimental MS/MS spectra. 23624262 2 111 theme bioinformatics 444:457 arg1 tools 459:463 accurate bioinformatics tools 435:463 accurate bioinformatics tools for data deposition and analysis 435:496 A major challenge in glycomics research is to provide and maintain high-quality datasets that will offer the necessary diversity to support the development of accurate bioinformatics tools for data deposition and analysis. 23624262 5 112 theme available 1131:1139 arg1 standards 1157:1165 the same 23 commercially available oligosaccharide standards 1106:1165 the same 23 commercially available oligosaccharide standards 1106:1165 In this context, an independent consortium of three laboratories was established to analyze the same 23 commercially available oligosaccharide standards, all by using graphitized carbon-liquid chromatography (LC) electrospray ionization (ESI) ion trap mass spectrometry in the negative ion mode. 23624262 3 113 theme MS/MS 625:629 arg1 library 631:637 a comprehensive LC MS/MS library 606:637 a comprehensive LC MS/MS library of N- and O- linked glycans released from glycoproteins that have been annotated with glycosidic and cross-ring fragmentation ions, retention times, and associated experimental metadata descriptions 606:836 The role of UniCarb-DB, as an archival database, is to provide the glycomics community with open-access to a comprehensive LC MS/MS library of N- and O- linked glycans released from glycoproteins that have been annotated with glycosidic and cross-ring fragmentation ions, retention times, and associated experimental metadata descriptions. 23624262 3 114 theme linked 652:657 arg1 glycans 659:665 O- linked glycans 649:665 O- linked glycans released from glycoproteins that have been annotated with glycosidic and cross-ring fragmentation ions, retention times, and associated experimental metadata descriptions 649:836 The role of UniCarb-DB, as an archival database, is to provide the glycomics community with open-access to a comprehensive LC MS/MS library of N- and O- linked glycans released from glycoproteins that have been annotated with glycosidic and cross-ring fragmentation ions, retention times, and associated experimental metadata descriptions. 23624262 5 115 theme ionization 1240:1249 arg1 spectrometry 1271:1282 graphitized carbon-liquid chromatography (LC) electrospray ionization (ESI) ion trap mass spectrometry 1181:1282 graphitized carbon-liquid chromatography (LC) electrospray ionization (ESI) ion trap mass spectrometry in the negative ion mode 1181:1307 In this context, an independent consortium of three laboratories was established to analyze the same 23 commercially available oligosaccharide standards, all by using graphitized carbon-liquid chromatography (LC) electrospray ionization (ESI) ion trap mass spectrometry in the negative ion mode. 26801611 8 0 theme little 1194:1199 arg1 influence 1201:1209 little influence 1194:1209 little influence 1194:1209 Overexpression of GnT-III promotes the cell migration in glioma cells U-251 and hepatoma cells HepG2, although it has little influence in human breast cancer cell MDA-MB-231 and gastric cancer cell MKN-45. 26801611 3 1 theme hepatomas 540:548 arg1 glioma 551:556 human hepatomas, glioma, and ovarian cancers 534:577 glioma 551:556 However, these results seem controversial to the clinical observations for the increased expression of GnT-III in human hepatomas, glioma, and ovarian cancers. 26801611 8 2 dep cancer 1227:1232 arg1 MKN-45 1274:1279 cell MKN-45 1269:1279 cell MKN-45 1269:1279 Overexpression of GnT-III promotes the cell migration in glioma cells U-251 and hepatoma cells HepG2, although it has little influence in human breast cancer cell MDA-MB-231 and gastric cancer cell MKN-45. 26801611 8 2 dep cancer 1227:1232 arg1 MDA-MB-231 1239:1248 cell MDA-MB-231 1234:1248 cell MDA-MB-231 1234:1248 Overexpression of GnT-III promotes the cell migration in glioma cells U-251 and hepatoma cells HepG2, although it has little influence in human breast cancer cell MDA-MB-231 and gastric cancer cell MKN-45. 26801611 8 3 theme GnT-III 1094:1100 arg1 Overexpression 1076:1089 Overexpression 1076:1089 Overexpression of GnT-III 1076:1100 Overexpression of GnT-III promotes the cell migration in glioma cells U-251 and hepatoma cells HepG2, although it has little influence in human breast cancer cell MDA-MB-231 and gastric cancer cell MKN-45. 26801611 2 4 theme multiple 389:396 arg1 types 398:402 multiple types 389:402 multiple types of tumor cells 389:417 Overexpression of GnT-III inhibited migration in multiple types of tumor cells. 26801611 5 5 theme GnT-III 754:760 arg1 overexpression 736:749 overexpression 736:749 overexpression of GnT-III 736:760 In detail, we show that overexpression of GnT-III significantly inhibits α2,3-sialylation but not α2,6-sialylation. 26801611 9 6 theme α2,6-hyposialylated 1394:1412 arg1 cells 1422:1426 the α2,6-hyposialylated HeLa-S3 cells 1390:1426 the α2,6-hyposialylated HeLa-S3 cells 1390:1426 Interestingly, up-regulation of α2,6-sialylation by overexpressing β-galactoside α2,6-sialyltranferase 1 in the α2,6-hyposialylated HeLa-S3 cells abolishes the anti-migratory effects of GnT-III. 26801611 8 7 theme cell 1115:1118 arg1 migration 1120:1128 the cell migration 1111:1128 the cell migration in glioma cells U-251 and hepatoma cells HepG2 1111:1175 Overexpression of GnT-III promotes the cell migration in glioma cells U-251 and hepatoma cells HepG2, although it has little influence in human breast cancer cell MDA-MB-231 and gastric cancer cell MKN-45. 26801611 7 8 theme tumor 1031:1035 arg1 cells 1037:1041 tumor cells 1031:1041 tumor cells that are highly α2,6-sialylated 1031:1073 In contrast, the effects of GnT-III overexpression are variable in tumor cells that are highly α2,6-sialylated. 26801611 10 9 gly α2,6-hypersialylated 1576:1595 arg1 cells 1603:1607 α2,6-hypersialylated HepG2 cells 1576:1607 α2,6-hypersialylated HepG2 cells 1576:1607 Conversely, depletion of α2,6-sialylation by knock-out of β-galactoside α2,6-sialyltranferase 1 in α2,6-hypersialylated HepG2 cells endows GnT-III with the anti-migratory ability. 26801611 8 10 from migration 1120:1128 arg1 cells 1165:1169 hepatoma cells 1156:1169 hepatoma cells 1156:1169 Overexpression of GnT-III promotes the cell migration in glioma cells U-251 and hepatoma cells HepG2, although it has little influence in human breast cancer cell MDA-MB-231 and gastric cancer cell MKN-45. 26801611 8 10 from migration 1120:1128 arg1 cells 1140:1144 glioma cells U-251 and hepatoma cells HepG2 1133:1175 cells 1140:1144 Overexpression of GnT-III promotes the cell migration in glioma cells U-251 and hepatoma cells HepG2, although it has little influence in human breast cancer cell MDA-MB-231 and gastric cancer cell MKN-45. 26801611 0 11 theme Cell 112:115 arg1 Migration 117:125 Cell Migration 112:125 Cell Migration 112:125 Expression of N-Acetylglucosaminyltransferase III Suppresses α2,3-Sialylation, and Its Distinctive Functions in Cell Migration Are Attributed to α2,6-Sialylation Levels. 26801611 9 12 theme HeLa-S3 1414:1420 arg1 cells 1422:1426 the α2,6-hyposialylated HeLa-S3 cells 1390:1426 the α2,6-hyposialylated HeLa-S3 cells 1390:1426 Interestingly, up-regulation of α2,6-sialylation by overexpressing β-galactoside α2,6-sialyltranferase 1 in the α2,6-hyposialylated HeLa-S3 cells abolishes the anti-migratory effects of GnT-III. 26801611 10 13 theme α2,6-sialylation 1502:1517 arg1 depletion 1489:1497 depletion 1489:1497 depletion of α2,6-sialylation by knock-out of β-galactoside α2,6-sialyltranferase 1 in α2,6-hypersialylated HepG2 cells 1489:1607 Conversely, depletion of α2,6-sialylation by knock-out of β-galactoside α2,6-sialyltranferase 1 in α2,6-hypersialylated HepG2 cells endows GnT-III with the anti-migratory ability. 26801611 8 14 dep cells 1140:1144 arg1 HepG2 1171:1175 HepG2 1171:1175 HepG2 1171:1175 Overexpression of GnT-III promotes the cell migration in glioma cells U-251 and hepatoma cells HepG2, although it has little influence in human breast cancer cell MDA-MB-231 and gastric cancer cell MKN-45. 26801611 3 15 theme GnT-III 523:529 arg1 expression 509:518 the increased expression 495:518 the increased expression of GnT-III in human hepatomas, glioma, and ovarian cancers 495:577 However, these results seem controversial to the clinical observations for the increased expression of GnT-III in human hepatomas, glioma, and ovarian cancers. 26801611 8 16 theme cell 1234:1237 arg1 MDA-MB-231 1239:1248 cell MDA-MB-231 1234:1248 cell MDA-MB-231 1234:1248 Overexpression of GnT-III promotes the cell migration in glioma cells U-251 and hepatoma cells HepG2, although it has little influence in human breast cancer cell MDA-MB-231 and gastric cancer cell MKN-45. 26801611 10 17 theme α2,6-hypersialylated 1576:1595 arg1 cells 1603:1607 α2,6-hypersialylated HepG2 cells 1576:1607 α2,6-hypersialylated HepG2 cells 1576:1607 Conversely, depletion of α2,6-sialylation by knock-out of β-galactoside α2,6-sialyltranferase 1 in α2,6-hypersialylated HepG2 cells endows GnT-III with the anti-migratory ability. 26801611 6 18 theme cells 853:857 arg1 ability 842:848 The migratory ability 828:848 The migratory ability of cells without or with a low level of α2,6-sialylation 828:905 The migratory ability of cells without or with a low level of α2,6-sialylation is consistently suppressed after GnT-III overexpression. 26801611 10 19 theme HepG2 1597:1601 arg1 cells 1603:1607 α2,6-hypersialylated HepG2 cells 1576:1607 α2,6-hypersialylated HepG2 cells 1576:1607 Conversely, depletion of α2,6-sialylation by knock-out of β-galactoside α2,6-sialyltranferase 1 in α2,6-hypersialylated HepG2 cells endows GnT-III with the anti-migratory ability. 26801611 3 20 theme clinical 469:476 arg1 observations 478:489 the clinical observations 465:489 the clinical observations for the increased expression of GnT-III in human hepatomas, glioma, and ovarian cancers 465:577 However, these results seem controversial to the clinical observations for the increased expression of GnT-III in human hepatomas, glioma, and ovarian cancers. 26801611 6 21 theme GnT-III 940:946 arg1 overexpression 948:961 GnT-III overexpression 940:961 GnT-III overexpression 940:961 The migratory ability of cells without or with a low level of α2,6-sialylation is consistently suppressed after GnT-III overexpression. 26801611 7 22 theme GnT-III 992:998 arg1 overexpression 1000:1013 GnT-III overexpression 992:1013 GnT-III overexpression 992:1013 In contrast, the effects of GnT-III overexpression are variable in tumor cells that are highly α2,6-sialylated. 26801611 3 23 theme ovarian 563:569 arg1 cancers 571:577 human hepatomas, glioma, and ovarian cancers 534:577 cancers 571:577 However, these results seem controversial to the clinical observations for the increased expression of GnT-III in human hepatomas, glioma, and ovarian cancers. 26801611 11 24 from roles 1859:1863 arg1 metastasis 1885:1894 tumor metastasis 1879:1894 tumor metastasis 1879:1894 Taken together, our data clearly demonstrate that high expression of α2,6-sialylation on the cell surface could affect the anti-migratory role of GnT-III, which provides an insight into the mechanistic roles of GnT-III in tumor metastasis. 26801611 9 25 theme GnT-III 1468:1474 arg1 effects 1457:1463 the anti-migratory effects 1438:1463 the anti-migratory effects of GnT-III 1438:1474 Interestingly, up-regulation of α2,6-sialylation by overexpressing β-galactoside α2,6-sialyltranferase 1 in the α2,6-hyposialylated HeLa-S3 cells abolishes the anti-migratory effects of GnT-III. 26801611 7 26 theme overexpression 1000:1013 arg1 variable 1019:1026 variable 1019:1026 variable 1019:1026 In contrast, the effects of GnT-III overexpression are variable in tumor cells that are highly α2,6-sialylated. 26801611 7 26 theme overexpression 1000:1013 arg1 effects 981:987 the effects 977:987 the effects of GnT-III overexpression 977:1013 In contrast, the effects of GnT-III overexpression are variable in tumor cells that are highly α2,6-sialylated. 26801611 11 27 theme cell 1750:1753 arg1 surface 1755:1761 the cell surface 1746:1761 the cell surface 1746:1761 Taken together, our data clearly demonstrate that high expression of α2,6-sialylation on the cell surface could affect the anti-migratory role of GnT-III, which provides an insight into the mechanistic roles of GnT-III in tumor metastasis. 26801611 9 28 theme anti-migratory 1442:1455 arg1 effects 1457:1463 the anti-migratory effects 1438:1463 the anti-migratory effects of GnT-III 1438:1474 Interestingly, up-regulation of α2,6-sialylation by overexpressing β-galactoside α2,6-sialyltranferase 1 in the α2,6-hyposialylated HeLa-S3 cells abolishes the anti-migratory effects of GnT-III. 26801611 8 29 theme glioma 1133:1138 arg1 cells 1140:1144 glioma cells U-251 and hepatoma cells HepG2 1133:1175 cells 1140:1144 Overexpression of GnT-III promotes the cell migration in glioma cells U-251 and hepatoma cells HepG2, although it has little influence in human breast cancer cell MDA-MB-231 and gastric cancer cell MKN-45. 26801611 6 30 theme migratory 832:840 arg1 ability 842:848 The migratory ability 828:848 The migratory ability of cells without or with a low level of α2,6-sialylation 828:905 The migratory ability of cells without or with a low level of α2,6-sialylation is consistently suppressed after GnT-III overexpression. 26801611 7 31 from contrast 967:974 arg1 variable 1019:1026 variable 1019:1026 variable 1019:1026 In contrast, the effects of GnT-III overexpression are variable in tumor cells that are highly α2,6-sialylated. 26801611 7 31 from contrast 967:974 arg1 effects 981:987 the effects 977:987 the effects of GnT-III overexpression 977:1013 In contrast, the effects of GnT-III overexpression are variable in tumor cells that are highly α2,6-sialylated. 26801611 2 32 theme cells 413:417 arg1 types 398:402 multiple types 389:402 multiple types of tumor cells 389:417 Overexpression of GnT-III inhibited migration in multiple types of tumor cells. 26801611 10 33 theme β-galactoside 1535:1547 arg1 α2,6-sialyltranferase 1549:1569 β-galactoside α2,6-sialyltranferase 1 1535:1571 β-galactoside α2,6-sialyltranferase 1 1535:1571 Conversely, depletion of α2,6-sialylation by knock-out of β-galactoside α2,6-sialyltranferase 1 in α2,6-hypersialylated HepG2 cells endows GnT-III with the anti-migratory ability. 26801611 0 34 theme α2,6-Sialylation 145:160 arg1 Levels 162:167 α2,6-Sialylation Levels 145:167 α2,6-Sialylation Levels 145:167 Expression of N-Acetylglucosaminyltransferase III Suppresses α2,3-Sialylation, and Its Distinctive Functions in Cell Migration Are Attributed to α2,6-Sialylation Levels. 26801611 8 35 contain has 1190:1192 arg2 influence 1201:1209 little influence 1194:1209 little influence 1194:1209 Overexpression of GnT-III promotes the cell migration in glioma cells U-251 and hepatoma cells HepG2, although it has little influence in human breast cancer cell MDA-MB-231 and gastric cancer cell MKN-45. 26801611 8 35 contain has 1190:1192 arg1 it 1187:1188 it 1187:1188 it 1187:1188 Overexpression of GnT-III promotes the cell migration in glioma cells U-251 and hepatoma cells HepG2, although it has little influence in human breast cancer cell MDA-MB-231 and gastric cancer cell MKN-45. 26801611 3 36 theme increased 499:507 arg1 expression 509:518 the increased expression 495:518 the increased expression of GnT-III in human hepatomas, glioma, and ovarian cancers 495:577 However, these results seem controversial to the clinical observations for the increased expression of GnT-III in human hepatomas, glioma, and ovarian cancers. 26801611 0 37 theme N-Acetylglucosaminyltransferase 14:44 arg1 Expression 0:9 Expression 0:9 Expression of N-Acetylglucosaminyltransferase III 0:48 Expression of N-Acetylglucosaminyltransferase III Suppresses α2,3-Sialylation, and Its Distinctive Functions in Cell Migration Are Attributed to α2,6-Sialylation Levels. 26801611 9 38 theme β-galactoside 1349:1361 arg1 α2,6-sialyltranferase 1363:1383 β-galactoside α2,6-sialyltranferase 1 1349:1385 β-galactoside α2,6-sialyltranferase 1 1349:1385 Interestingly, up-regulation of α2,6-sialylation by overexpressing β-galactoside α2,6-sialyltranferase 1 in the α2,6-hyposialylated HeLa-S3 cells abolishes the anti-migratory effects of GnT-III. 26801611 9 39 theme α2,6-sialylation 1314:1329 arg1 up-regulation 1297:1309 up-regulation 1297:1309 up-regulation of α2,6-sialylation by overexpressing β-galactoside α2,6-sialyltranferase 1 in the α2,6-hyposialylated HeLa-S3 cells 1297:1426 Interestingly, up-regulation of α2,6-sialylation by overexpressing β-galactoside α2,6-sialyltranferase 1 in the α2,6-hyposialylated HeLa-S3 cells abolishes the anti-migratory effects of GnT-III. 26801611 7 40 from cells 1037:1041 arg1 variable 1019:1026 variable 1019:1026 variable 1019:1026 In contrast, the effects of GnT-III overexpression are variable in tumor cells that are highly α2,6-sialylated. 26801611 7 40 from cells 1037:1041 arg1 effects 981:987 the effects 977:987 the effects of GnT-III overexpression 977:1013 In contrast, the effects of GnT-III overexpression are variable in tumor cells that are highly α2,6-sialylated. 26801611 11 41 theme GnT-III 1868:1874 arg1 roles 1859:1863 the mechanistic roles 1843:1863 the mechanistic roles of GnT-III in tumor metastasis 1843:1894 Taken together, our data clearly demonstrate that high expression of α2,6-sialylation on the cell surface could affect the anti-migratory role of GnT-III, which provides an insight into the mechanistic roles of GnT-III in tumor metastasis. 26801611 10 42 theme α2,6-sialyltranferase 1549:1569 arg1 knock-out 1522:1530 knock-out 1522:1530 knock-out of β-galactoside α2,6-sialyltranferase 1 in α2,6-hypersialylated HepG2 cells 1522:1607 Conversely, depletion of α2,6-sialylation by knock-out of β-galactoside α2,6-sialyltranferase 1 in α2,6-hypersialylated HepG2 cells endows GnT-III with the anti-migratory ability. 26801611 1 43 theme metastasis 317:326 arg1 N-Acetylglucosaminyltransferase 170:200 N-Acetylglucosaminyltransferase III 170:204 N-Acetylglucosaminyltransferase III (GnT-III) 170:214 N-Acetylglucosaminyltransferase III (GnT-III), which catalyzes the addition of the bisecting GlcNAc branch on N-glycans, is usually described as a metastasis suppressor. 26801611 1 43 theme metastasis 317:326 arg1 suppressor 328:337 a metastasis suppressor 315:337 a metastasis suppressor 315:337 N-Acetylglucosaminyltransferase III (GnT-III), which catalyzes the addition of the bisecting GlcNAc branch on N-glycans, is usually described as a metastasis suppressor. 26801611 1 44 from N-glycans 280:288 arg1 addition 237:244 the addition 233:244 the addition of the bisecting GlcNAc branch on N-glycans 233:288 N-Acetylglucosaminyltransferase III (GnT-III), which catalyzes the addition of the bisecting GlcNAc branch on N-glycans, is usually described as a metastasis suppressor. 26801611 0 45 from Functions 99:107 arg1 Migration 117:125 Cell Migration 112:125 Cell Migration 112:125 Expression of N-Acetylglucosaminyltransferase III Suppresses α2,3-Sialylation, and Its Distinctive Functions in Cell Migration Are Attributed to α2,6-Sialylation Levels. 26801611 4 46 theme sialylation 699:709 arg1 pattern 683:689 the different expression pattern 658:689 the different expression pattern of cell sialylation 658:709 Here, we present evidence that these inconsistencies are mainly attributed to the different expression pattern of cell sialylation. 26801611 11 47 theme high 1707:1710 arg1 expression 1712:1721 high expression 1707:1721 high expression of α2,6-sialylation on the cell surface 1707:1761 Taken together, our data clearly demonstrate that high expression of α2,6-sialylation on the cell surface could affect the anti-migratory role of GnT-III, which provides an insight into the mechanistic roles of GnT-III in tumor metastasis. 26801611 4 48 theme cell 694:697 arg1 sialylation 699:709 cell sialylation 694:709 cell sialylation 694:709 Here, we present evidence that these inconsistencies are mainly attributed to the different expression pattern of cell sialylation. 26801611 8 49 theme hepatoma 1156:1163 arg1 cells 1165:1169 hepatoma cells 1156:1169 hepatoma cells 1156:1169 Overexpression of GnT-III promotes the cell migration in glioma cells U-251 and hepatoma cells HepG2, although it has little influence in human breast cancer cell MDA-MB-231 and gastric cancer cell MKN-45. 26801611 11 50 theme GnT-III 1803:1809 arg1 role 1795:1798 the anti-migratory role 1776:1798 the anti-migratory role 1776:1798 Taken together, our data clearly demonstrate that high expression of α2,6-sialylation on the cell surface could affect the anti-migratory role of GnT-III, which provides an insight into the mechanistic roles of GnT-III in tumor metastasis. 26801611 10 51 from knock-out 1522:1530 arg1 cells 1603:1607 α2,6-hypersialylated HepG2 cells 1576:1607 α2,6-hypersialylated HepG2 cells 1576:1607 Conversely, depletion of α2,6-sialylation by knock-out of β-galactoside α2,6-sialyltranferase 1 in α2,6-hypersialylated HepG2 cells endows GnT-III with the anti-migratory ability. 26801611 4 52 theme expression 672:681 arg1 pattern 683:689 the different expression pattern 658:689 the different expression pattern of cell sialylation 658:709 Here, we present evidence that these inconsistencies are mainly attributed to the different expression pattern of cell sialylation. 26801611 8 53 theme breast 1220:1225 arg1 cancer 1227:1232 human breast cancer cell MDA-MB-231 and gastric cancer cell MKN-45 1214:1279 cancer 1227:1232 Overexpression of GnT-III promotes the cell migration in glioma cells U-251 and hepatoma cells HepG2, although it has little influence in human breast cancer cell MDA-MB-231 and gastric cancer cell MKN-45. 26801611 1 54 from branch 270:275 arg1 N-glycans 280:288 N-glycans 280:288 N-glycans 280:288 N-Acetylglucosaminyltransferase III (GnT-III), which catalyzes the addition of the bisecting GlcNAc branch on N-glycans, is usually described as a metastasis suppressor. 26801611 6 55 theme α2,6-sialylation 890:905 arg1 level 881:885 a low level 875:885 a low level of α2,6-sialylation 875:905 The migratory ability of cells without or with a low level of α2,6-sialylation is consistently suppressed after GnT-III overexpression. 26801611 11 56 from expression 1712:1721 arg1 surface 1755:1761 the cell surface 1746:1761 the cell surface 1746:1761 Taken together, our data clearly demonstrate that high expression of α2,6-sialylation on the cell surface could affect the anti-migratory role of GnT-III, which provides an insight into the mechanistic roles of GnT-III in tumor metastasis. 26801611 10 57 theme anti-migratory 1633:1646 arg1 ability 1648:1654 the anti-migratory ability 1629:1654 the anti-migratory ability 1629:1654 Conversely, depletion of α2,6-sialylation by knock-out of β-galactoside α2,6-sialyltranferase 1 in α2,6-hypersialylated HepG2 cells endows GnT-III with the anti-migratory ability. 26801611 11 58 theme tumor 1879:1883 arg1 metastasis 1885:1894 tumor metastasis 1879:1894 tumor metastasis 1879:1894 Taken together, our data clearly demonstrate that high expression of α2,6-sialylation on the cell surface could affect the anti-migratory role of GnT-III, which provides an insight into the mechanistic roles of GnT-III in tumor metastasis. 26801611 8 59 theme cell 1269:1272 arg1 MKN-45 1274:1279 cell MKN-45 1269:1279 cell MKN-45 1269:1279 Overexpression of GnT-III promotes the cell migration in glioma cells U-251 and hepatoma cells HepG2, although it has little influence in human breast cancer cell MDA-MB-231 and gastric cancer cell MKN-45. 26801611 3 60 theme human 534:538 arg1 glioma 551:556 human hepatomas, glioma, and ovarian cancers 534:577 glioma 551:556 However, these results seem controversial to the clinical observations for the increased expression of GnT-III in human hepatomas, glioma, and ovarian cancers. 26801611 7 61 gly α2,6-sialylated 1059:1073 arg1 cells 1037:1041 tumor cells 1031:1041 tumor cells that are highly α2,6-sialylated 1031:1073 In contrast, the effects of GnT-III overexpression are variable in tumor cells that are highly α2,6-sialylated. 26801611 11 62 theme α2,6-sialylation 1726:1741 arg1 expression 1712:1721 high expression 1707:1721 high expression of α2,6-sialylation on the cell surface 1707:1761 Taken together, our data clearly demonstrate that high expression of α2,6-sialylation on the cell surface could affect the anti-migratory role of GnT-III, which provides an insight into the mechanistic roles of GnT-III in tumor metastasis. 26801611 1 63 from addition 237:244 arg1 N-glycans 280:288 N-glycans 280:288 N-glycans 280:288 N-Acetylglucosaminyltransferase III (GnT-III), which catalyzes the addition of the bisecting GlcNAc branch on N-glycans, is usually described as a metastasis suppressor. 26801611 9 64 gly α2,6-hyposialylated 1394:1412 arg1 cells 1422:1426 the α2,6-hyposialylated HeLa-S3 cells 1390:1426 the α2,6-hyposialylated HeLa-S3 cells 1390:1426 Interestingly, up-regulation of α2,6-sialylation by overexpressing β-galactoside α2,6-sialyltranferase 1 in the α2,6-hyposialylated HeLa-S3 cells abolishes the anti-migratory effects of GnT-III. 26801611 1 65 theme bisecting 253:261 arg1 GlcNAc 263:268 bisecting GlcNAc 253:268 the bisecting GlcNAc branch on N-glycans 249:288 N-Acetylglucosaminyltransferase III (GnT-III), which catalyzes the addition of the bisecting GlcNAc branch on N-glycans, is usually described as a metastasis suppressor. 26801611 3 66 from expression 509:518 arg1 cancers 571:577 human hepatomas, glioma, and ovarian cancers 534:577 cancers 571:577 However, these results seem controversial to the clinical observations for the increased expression of GnT-III in human hepatomas, glioma, and ovarian cancers. 26801611 3 66 from expression 509:518 arg1 glioma 551:556 human hepatomas, glioma, and ovarian cancers 534:577 glioma 551:556 However, these results seem controversial to the clinical observations for the increased expression of GnT-III in human hepatomas, glioma, and ovarian cancers. 26801611 6 67 theme low 877:879 arg1 level 881:885 a low level 875:885 a low level of α2,6-sialylation 875:905 The migratory ability of cells without or with a low level of α2,6-sialylation is consistently suppressed after GnT-III overexpression. 26801611 11 68 theme anti-migratory 1780:1793 arg1 role 1795:1798 the anti-migratory role 1776:1798 the anti-migratory role 1776:1798 Taken together, our data clearly demonstrate that high expression of α2,6-sialylation on the cell surface could affect the anti-migratory role of GnT-III, which provides an insight into the mechanistic roles of GnT-III in tumor metastasis. 26801611 2 69 theme GnT-III 358:364 arg1 Overexpression 340:353 Overexpression 340:353 Overexpression of GnT-III 340:364 Overexpression of GnT-III inhibited migration in multiple types of tumor cells. 26801611 1 70 theme GlcNAc 263:268 arg1 branch 270:275 the bisecting GlcNAc branch 249:275 the bisecting GlcNAc branch on N-glycans 249:288 N-Acetylglucosaminyltransferase III (GnT-III), which catalyzes the addition of the bisecting GlcNAc branch on N-glycans, is usually described as a metastasis suppressor. 26801611 0 71 theme Distinctive 87:97 arg1 Functions 99:107 Its Distinctive Functions 83:107 Its Distinctive Functions in Cell Migration 83:125 Expression of N-Acetylglucosaminyltransferase III Suppresses α2,3-Sialylation, and Its Distinctive Functions in Cell Migration Are Attributed to α2,6-Sialylation Levels. 26801611 4 72 theme different 662:670 arg1 pattern 683:689 the different expression pattern 658:689 the different expression pattern of cell sialylation 658:709 Here, we present evidence that these inconsistencies are mainly attributed to the different expression pattern of cell sialylation. 26801611 2 73 theme tumor 407:411 arg1 cells 413:417 tumor cells 407:417 tumor cells 407:417 Overexpression of GnT-III inhibited migration in multiple types of tumor cells. 26801611 1 74 theme branch 270:275 arg1 addition 237:244 the addition 233:244 the addition of the bisecting GlcNAc branch on N-glycans 233:288 N-Acetylglucosaminyltransferase III (GnT-III), which catalyzes the addition of the bisecting GlcNAc branch on N-glycans, is usually described as a metastasis suppressor. 26801611 8 75 theme gastric 1254:1260 arg1 cancer 1262:1267 gastric cancer 1254:1267 gastric cancer 1254:1267 Overexpression of GnT-III promotes the cell migration in glioma cells U-251 and hepatoma cells HepG2, although it has little influence in human breast cancer cell MDA-MB-231 and gastric cancer cell MKN-45. 26801611 7 76 from variable 1019:1026 arg1 contrast 967:974 contrast 967:974 contrast 967:974 In contrast, the effects of GnT-III overexpression are variable in tumor cells that are highly α2,6-sialylated. 26801611 7 76 from variable 1019:1026 arg1 cells 1037:1041 tumor cells 1031:1041 tumor cells that are highly α2,6-sialylated 1031:1073 In contrast, the effects of GnT-III overexpression are variable in tumor cells that are highly α2,6-sialylated. 26801611 11 77 theme mechanistic 1847:1857 arg1 roles 1859:1863 the mechanistic roles 1843:1863 the mechanistic roles of GnT-III in tumor metastasis 1843:1894 Taken together, our data clearly demonstrate that high expression of α2,6-sialylation on the cell surface could affect the anti-migratory role of GnT-III, which provides an insight into the mechanistic roles of GnT-III in tumor metastasis. 26801611 8 78 theme human 1214:1218 arg1 cancer 1227:1232 human breast cancer cell MDA-MB-231 and gastric cancer cell MKN-45 1214:1279 cancer 1227:1232 Overexpression of GnT-III promotes the cell migration in glioma cells U-251 and hepatoma cells HepG2, although it has little influence in human breast cancer cell MDA-MB-231 and gastric cancer cell MKN-45. 29269249 0 0 theme antigen-adjuvant 97:112 arg1 protein 121:127 the recombinant PfCelTOS-Il2 antigen-adjuvant fusion protein 68:127 the recombinant PfCelTOS-Il2 antigen-adjuvant fusion protein 68:127 Engineering the chloroplast of Chlamydomonas reinhardtii to express the recombinant PfCelTOS-Il2 antigen-adjuvant fusion protein. 29269249 3 1 theme life 322:325 arg1 cycle 327:331 a complex life cycle 312:331 a complex life cycle 312:331 Malaria parasite has a complex life cycle and attempts are being made to develop vaccines that target each stage of the life cycle. 29269249 4 2 from conditions 594:603 arg1 stable 567:572 stable 567:572 stable 567:572 Oral vaccines seem to be more feasible to implement in poor countries, since they are relatively inexpensive, needle-free administrated, mostly stable at non-refrigerated conditions and painless. 29269249 7 3 theme disulfide 1020:1028 arg1 formation 1035:1043 disulfide bond formation 1020:1043 disulfide bond formation 1020:1043 Moreover, C. reinhardtii chloroplast is an attractive platform for expressing malaria antigens because it is capable of folding complex proteins, including those requiring disulfide bond formation, while lacking the ability to glycosylate proteins; a valuable quality of any malaria protein expression system, since the Plasmodium parasite lacks N-linked glycosylation machinery. 29269249 1 4 theme large 172:176 arg1 impact 187:192 a large negative impact 170:192 a large negative impact on economic growth 170:211 Malaria is an infectious disease having a large negative impact on economic growth. 29269249 7 5 theme malaria 926:932 arg1 antigens 934:941 expressing malaria antigens 915:941 expressing malaria antigens 915:941 Moreover, C. reinhardtii chloroplast is an attractive platform for expressing malaria antigens because it is capable of folding complex proteins, including those requiring disulfide bond formation, while lacking the ability to glycosylate proteins; a valuable quality of any malaria protein expression system, since the Plasmodium parasite lacks N-linked glycosylation machinery. 29269249 0 6 theme PfCelTOS-Il2 84:95 arg1 protein 121:127 the recombinant PfCelTOS-Il2 antigen-adjuvant fusion protein 68:127 the recombinant PfCelTOS-Il2 antigen-adjuvant fusion protein 68:127 Engineering the chloroplast of Chlamydomonas reinhardtii to express the recombinant PfCelTOS-Il2 antigen-adjuvant fusion protein. 29269249 7 7 theme system 1150:1155 arg1 it 951:952 it 951:952 it 951:952 Moreover, C. reinhardtii chloroplast is an attractive platform for expressing malaria antigens because it is capable of folding complex proteins, including those requiring disulfide bond formation, while lacking the ability to glycosylate proteins; a valuable quality of any malaria protein expression system, since the Plasmodium parasite lacks N-linked glycosylation machinery. 29269249 7 7 theme system 1150:1155 arg1 quality 1108:1114 a valuable quality 1097:1114 a valuable quality of any malaria protein expression system 1097:1155 Moreover, C. reinhardtii chloroplast is an attractive platform for expressing malaria antigens because it is capable of folding complex proteins, including those requiring disulfide bond formation, while lacking the ability to glycosylate proteins; a valuable quality of any malaria protein expression system, since the Plasmodium parasite lacks N-linked glycosylation machinery. 29269249 8 8 theme reinhardtii 1516:1526 arg1 chloroplast 1498:1508 the chloroplast 1494:1508 the chloroplast of C. reinhardtii 1494:1526 As a first step towards developing an oral vaccine candidate against malaria, here, we expressed a fusion protein consisting of PfCelTOS, a candidate for pre-erythrocytic and transmission-blocking vaccines, fused to human interleukin-2 (IL-2) as vaccine adjuvant in the chloroplast of C. reinhardtii. 29269249 1 9 theme negative 178:185 arg1 impact 187:192 a large negative impact 170:192 a large negative impact on economic growth 170:211 Malaria is an infectious disease having a large negative impact on economic growth. 29269249 7 10 theme complex 976:982 arg1 proteins 984:991 folding complex proteins 968:991 folding complex proteins 968:991 Moreover, C. reinhardtii chloroplast is an attractive platform for expressing malaria antigens because it is capable of folding complex proteins, including those requiring disulfide bond formation, while lacking the ability to glycosylate proteins; a valuable quality of any malaria protein expression system, since the Plasmodium parasite lacks N-linked glycosylation machinery. 29269249 7 10 theme complex 976:982 arg1 those 1004:1008 those 1004:1008 those 1004:1008 Moreover, C. reinhardtii chloroplast is an attractive platform for expressing malaria antigens because it is capable of folding complex proteins, including those requiring disulfide bond formation, while lacking the ability to glycosylate proteins; a valuable quality of any malaria protein expression system, since the Plasmodium parasite lacks N-linked glycosylation machinery. 29269249 5 11 theme suitable 652:659 arg1 hosts 666:670 suitable oral hosts 652:670 suitable oral hosts 652:670 By using recombinant technology, suitable oral hosts could serve as antigen delivering vehicles in developing oral vaccines. 29269249 5 11 theme suitable 652:659 arg1 vehicles 706:713 antigen delivering vehicles 687:713 antigen delivering vehicles in developing oral vaccines 687:741 By using recombinant technology, suitable oral hosts could serve as antigen delivering vehicles in developing oral vaccines. 29269249 7 12 theme proteins 984:991 arg1 capable 957:963 capable 957:963 capable 957:963 Moreover, C. reinhardtii chloroplast is an attractive platform for expressing malaria antigens because it is capable of folding complex proteins, including those requiring disulfide bond formation, while lacking the ability to glycosylate proteins; a valuable quality of any malaria protein expression system, since the Plasmodium parasite lacks N-linked glycosylation machinery. 29269249 9 13 theme recombinant 1562:1572 arg1 production 1582:1591 recombinant protein production 1562:1591 recombinant protein production 1562:1591 The effect of light and media on recombinant protein production and cell growth was then studied. 29269249 11 14 theme highest 1809:1815 arg1 density 1822:1828 the highest cell density 1805:1828 the highest cell density 1805:1828 Moreover, results showed that the highest cell density can be achieved using mixotrophy mode. 29269249 0 15 theme fusion 114:119 arg1 protein 121:127 the recombinant PfCelTOS-Il2 antigen-adjuvant fusion protein 68:127 the recombinant PfCelTOS-Il2 antigen-adjuvant fusion protein 68:127 Engineering the chloroplast of Chlamydomonas reinhardtii to express the recombinant PfCelTOS-Il2 antigen-adjuvant fusion protein. 29269249 5 16 theme delivering 695:704 arg1 hosts 666:670 suitable oral hosts 652:670 suitable oral hosts 652:670 By using recombinant technology, suitable oral hosts could serve as antigen delivering vehicles in developing oral vaccines. 29269249 5 16 theme delivering 695:704 arg1 vehicles 706:713 antigen delivering vehicles 687:713 antigen delivering vehicles in developing oral vaccines 687:741 By using recombinant technology, suitable oral hosts could serve as antigen delivering vehicles in developing oral vaccines. 29269249 5 17 theme oral 661:664 arg1 hosts 666:670 suitable oral hosts 652:670 suitable oral hosts 652:670 By using recombinant technology, suitable oral hosts could serve as antigen delivering vehicles in developing oral vaccines. 29269249 5 17 theme oral 661:664 arg1 vehicles 706:713 antigen delivering vehicles 687:713 antigen delivering vehicles in developing oral vaccines 687:741 By using recombinant technology, suitable oral hosts could serve as antigen delivering vehicles in developing oral vaccines. 29269249 6 18 theme expression 827:836 arg1 platform 838:845 oral recombinant protein expression platform 802:845 oral recombinant protein expression platform 802:845 Chlamydomonas reinhardtii offers beneficial attributes as oral recombinant protein expression platform. 29269249 9 19 theme protein 1574:1580 arg1 production 1582:1591 recombinant protein production 1562:1591 recombinant protein production 1562:1591 The effect of light and media on recombinant protein production and cell growth was then studied. 29269249 3 20 contain has 308:310 arg2 cycle 327:331 a complex life cycle 312:331 a complex life cycle 312:331 Malaria parasite has a complex life cycle and attempts are being made to develop vaccines that target each stage of the life cycle. 29269249 3 20 contain has 308:310 arg1 parasite 299:306 Malaria parasite 291:306 Malaria parasite 291:306 Malaria parasite has a complex life cycle and attempts are being made to develop vaccines that target each stage of the life cycle. 29269249 8 21 theme fusion 1327:1332 arg1 step 1239:1242 a first step 1231:1242 a first step towards developing an oral vaccine candidate against malaria 1231:1303 As a first step towards developing an oral vaccine candidate against malaria, here, we expressed a fusion protein consisting of PfCelTOS, a candidate for pre-erythrocytic and transmission-blocking vaccines, fused to human interleukin-2 (IL-2) as vaccine adjuvant in the chloroplast of C. reinhardtii. 29269249 8 21 theme fusion 1327:1332 arg1 protein 1334:1340 a fusion protein 1325:1340 a fusion protein consisting of PfCelTOS 1325:1363 As a first step towards developing an oral vaccine candidate against malaria, here, we expressed a fusion protein consisting of PfCelTOS, a candidate for pre-erythrocytic and transmission-blocking vaccines, fused to human interleukin-2 (IL-2) as vaccine adjuvant in the chloroplast of C. reinhardtii. 29269249 8 21 theme fusion 1327:1332 arg1 candidate 1368:1376 a candidate 1366:1376 a candidate for pre-erythrocytic and transmission-blocking vaccines 1366:1432 As a first step towards developing an oral vaccine candidate against malaria, here, we expressed a fusion protein consisting of PfCelTOS, a candidate for pre-erythrocytic and transmission-blocking vaccines, fused to human interleukin-2 (IL-2) as vaccine adjuvant in the chloroplast of C. reinhardtii. 29269249 7 22 theme malaria 1123:1129 arg1 system 1150:1155 any malaria protein expression system 1119:1155 any malaria protein expression system 1119:1155 Moreover, C. reinhardtii chloroplast is an attractive platform for expressing malaria antigens because it is capable of folding complex proteins, including those requiring disulfide bond formation, while lacking the ability to glycosylate proteins; a valuable quality of any malaria protein expression system, since the Plasmodium parasite lacks N-linked glycosylation machinery. 29269249 6 23 theme protein 819:825 arg1 platform 838:845 oral recombinant protein expression platform 802:845 oral recombinant protein expression platform 802:845 Chlamydomonas reinhardtii offers beneficial attributes as oral recombinant protein expression platform. 29269249 2 24 theme malaria 282:288 arg1 burden 272:277 the burden 268:277 the burden of malaria 268:288 Vaccines are considered as a novel strategy to reduce the burden of malaria. 29269249 1 25 theme economic 197:204 arg1 growth 206:211 economic growth 197:211 economic growth 197:211 Malaria is an infectious disease having a large negative impact on economic growth. 29269249 10 26 theme soluble 1700:1706 arg1 protein 1740:1746 a soluble, properly folded and functional protein 1698:1746 a soluble, properly folded and functional protein 1698:1746 Results demonstrated that expressed recombinant proteins accumulate as a soluble, properly folded and functional protein within algal chloroplasts. 29269249 11 27 theme cell 1817:1820 arg1 density 1822:1828 the highest cell density 1805:1828 the highest cell density 1805:1828 Moreover, results showed that the highest cell density can be achieved using mixotrophy mode. 29269249 7 28 theme protein 1131:1137 arg1 system 1150:1155 any malaria protein expression system 1119:1155 any malaria protein expression system 1119:1155 Moreover, C. reinhardtii chloroplast is an attractive platform for expressing malaria antigens because it is capable of folding complex proteins, including those requiring disulfide bond formation, while lacking the ability to glycosylate proteins; a valuable quality of any malaria protein expression system, since the Plasmodium parasite lacks N-linked glycosylation machinery. 29269249 6 29 theme recombinant 807:817 arg1 platform 838:845 oral recombinant protein expression platform 802:845 oral recombinant protein expression platform 802:845 Chlamydomonas reinhardtii offers beneficial attributes as oral recombinant protein expression platform. 29269249 8 30 theme vaccine 1271:1277 arg1 candidate 1279:1287 an oral vaccine candidate 1263:1287 an oral vaccine candidate against malaria 1263:1303 As a first step towards developing an oral vaccine candidate against malaria, here, we expressed a fusion protein consisting of PfCelTOS, a candidate for pre-erythrocytic and transmission-blocking vaccines, fused to human interleukin-2 (IL-2) as vaccine adjuvant in the chloroplast of C. reinhardtii. 29269249 9 31 theme media 1553:1557 arg1 effect 1533:1538 The effect 1529:1538 The effect of light and media on recombinant protein production and cell growth 1529:1607 The effect of light and media on recombinant protein production and cell growth was then studied. 29269249 1 32 contain having 163:168 arg2 impact 187:192 a large negative impact 170:192 a large negative impact on economic growth 170:211 Malaria is an infectious disease having a large negative impact on economic growth. 29269249 1 32 contain having 163:168 arg1 disease 155:161 an infectious disease 141:161 an infectious disease having a large negative impact on economic growth 141:211 Malaria is an infectious disease having a large negative impact on economic growth. 29269249 1 32 contain having 163:168 arg1 Malaria 130:136 Malaria 130:136 Malaria 130:136 Malaria is an infectious disease having a large negative impact on economic growth. 29269249 6 33 theme oral 802:805 arg1 platform 838:845 oral recombinant protein expression platform 802:845 oral recombinant protein expression platform 802:845 Chlamydomonas reinhardtii offers beneficial attributes as oral recombinant protein expression platform. 29269249 8 34 theme transmission-blocking 1403:1423 arg1 vaccines 1425:1432 pre-erythrocytic and transmission-blocking vaccines 1382:1432 pre-erythrocytic and transmission-blocking vaccines 1382:1432 As a first step towards developing an oral vaccine candidate against malaria, here, we expressed a fusion protein consisting of PfCelTOS, a candidate for pre-erythrocytic and transmission-blocking vaccines, fused to human interleukin-2 (IL-2) as vaccine adjuvant in the chloroplast of C. reinhardtii. 29269249 12 35 theme protein 1878:1884 arg1 accumulation 1886:1897 protein accumulation 1878:1897 protein accumulation 1878:1897 However, protein accumulation appears to be favored by cultivating in TAP medium in low light. 29269249 3 36 theme life 411:414 arg1 cycle 416:420 the life cycle 407:420 the life cycle 407:420 Malaria parasite has a complex life cycle and attempts are being made to develop vaccines that target each stage of the life cycle. 29269249 9 37 theme cell 1597:1600 arg1 growth 1602:1607 cell growth 1597:1607 cell growth 1597:1607 The effect of light and media on recombinant protein production and cell growth was then studied. 29269249 5 38 theme recombinant 628:638 arg1 technology 640:649 recombinant technology 628:649 recombinant technology 628:649 By using recombinant technology, suitable oral hosts could serve as antigen delivering vehicles in developing oral vaccines. 29269249 12 39 theme TAP 1939:1941 arg1 medium 1943:1948 TAP medium 1939:1948 TAP medium 1939:1948 However, protein accumulation appears to be favored by cultivating in TAP medium in low light. 29269249 7 40 theme C. 858:859 arg1 platform 902:909 an attractive platform 888:909 an attractive platform for expressing malaria antigens 888:941 Moreover, C. reinhardtii chloroplast is an attractive platform for expressing malaria antigens because it is capable of folding complex proteins, including those requiring disulfide bond formation, while lacking the ability to glycosylate proteins; a valuable quality of any malaria protein expression system, since the Plasmodium parasite lacks N-linked glycosylation machinery. 29269249 7 40 theme C. 858:859 arg1 chloroplast 873:883 C. reinhardtii chloroplast 858:883 C. reinhardtii chloroplast 858:883 Moreover, C. reinhardtii chloroplast is an attractive platform for expressing malaria antigens because it is capable of folding complex proteins, including those requiring disulfide bond formation, while lacking the ability to glycosylate proteins; a valuable quality of any malaria protein expression system, since the Plasmodium parasite lacks N-linked glycosylation machinery. 29269249 3 41 theme cycle 416:420 arg1 stage 398:402 each stage 393:402 each stage of the life cycle 393:420 Malaria parasite has a complex life cycle and attempts are being made to develop vaccines that target each stage of the life cycle. 29269249 7 42 theme N-linked 1194:1201 arg1 machinery 1217:1225 N-linked glycosylation machinery 1194:1225 N-linked glycosylation machinery 1194:1225 Moreover, C. reinhardtii chloroplast is an attractive platform for expressing malaria antigens because it is capable of folding complex proteins, including those requiring disulfide bond formation, while lacking the ability to glycosylate proteins; a valuable quality of any malaria protein expression system, since the Plasmodium parasite lacks N-linked glycosylation machinery. 29269249 11 43 theme mixotrophy 1852:1861 arg1 mode 1863:1866 mixotrophy mode 1852:1866 mixotrophy mode 1852:1866 Moreover, results showed that the highest cell density can be achieved using mixotrophy mode. 29269249 5 44 theme antigen 687:693 arg1 hosts 666:670 suitable oral hosts 652:670 suitable oral hosts 652:670 By using recombinant technology, suitable oral hosts could serve as antigen delivering vehicles in developing oral vaccines. 29269249 5 44 theme antigen 687:693 arg1 vehicles 706:713 antigen delivering vehicles 687:713 antigen delivering vehicles in developing oral vaccines 687:741 By using recombinant technology, suitable oral hosts could serve as antigen delivering vehicles in developing oral vaccines. 29269249 8 45 from vaccine 1474:1480 arg1 chloroplast 1498:1508 the chloroplast 1494:1508 the chloroplast of C. reinhardtii 1494:1526 As a first step towards developing an oral vaccine candidate against malaria, here, we expressed a fusion protein consisting of PfCelTOS, a candidate for pre-erythrocytic and transmission-blocking vaccines, fused to human interleukin-2 (IL-2) as vaccine adjuvant in the chloroplast of C. reinhardtii. 29269249 7 46 theme reinhardtii 861:871 arg1 platform 902:909 an attractive platform 888:909 an attractive platform for expressing malaria antigens 888:941 Moreover, C. reinhardtii chloroplast is an attractive platform for expressing malaria antigens because it is capable of folding complex proteins, including those requiring disulfide bond formation, while lacking the ability to glycosylate proteins; a valuable quality of any malaria protein expression system, since the Plasmodium parasite lacks N-linked glycosylation machinery. 29269249 7 46 theme reinhardtii 861:871 arg1 chloroplast 873:883 C. reinhardtii chloroplast 858:883 C. reinhardtii chloroplast 858:883 Moreover, C. reinhardtii chloroplast is an attractive platform for expressing malaria antigens because it is capable of folding complex proteins, including those requiring disulfide bond formation, while lacking the ability to glycosylate proteins; a valuable quality of any malaria protein expression system, since the Plasmodium parasite lacks N-linked glycosylation machinery. 29269249 7 47 theme glycosylation 1203:1215 arg1 machinery 1217:1225 N-linked glycosylation machinery 1194:1225 N-linked glycosylation machinery 1194:1225 Moreover, C. reinhardtii chloroplast is an attractive platform for expressing malaria antigens because it is capable of folding complex proteins, including those requiring disulfide bond formation, while lacking the ability to glycosylate proteins; a valuable quality of any malaria protein expression system, since the Plasmodium parasite lacks N-linked glycosylation machinery. 29269249 3 48 theme Malaria 291:297 arg1 parasite 299:306 Malaria parasite 291:306 Malaria parasite 291:306 Malaria parasite has a complex life cycle and attempts are being made to develop vaccines that target each stage of the life cycle. 29269249 8 49 theme adjuvant 1482:1489 arg1 vaccine 1474:1480 vaccine adjuvant 1474:1489 vaccine adjuvant in the chloroplast of C. reinhardtii 1474:1526 As a first step towards developing an oral vaccine candidate against malaria, here, we expressed a fusion protein consisting of PfCelTOS, a candidate for pre-erythrocytic and transmission-blocking vaccines, fused to human interleukin-2 (IL-2) as vaccine adjuvant in the chloroplast of C. reinhardtii. 29269249 0 50 theme reinhardtii 45:55 arg1 chloroplast 16:26 the chloroplast 12:26 the chloroplast of Chlamydomonas reinhardtii 12:55 Engineering the chloroplast of Chlamydomonas reinhardtii to express the recombinant PfCelTOS-Il2 antigen-adjuvant fusion protein. 29269249 7 51 theme attractive 891:900 arg1 platform 902:909 an attractive platform 888:909 an attractive platform for expressing malaria antigens 888:941 Moreover, C. reinhardtii chloroplast is an attractive platform for expressing malaria antigens because it is capable of folding complex proteins, including those requiring disulfide bond formation, while lacking the ability to glycosylate proteins; a valuable quality of any malaria protein expression system, since the Plasmodium parasite lacks N-linked glycosylation machinery. 29269249 7 51 theme attractive 891:900 arg1 chloroplast 873:883 C. reinhardtii chloroplast 858:883 C. reinhardtii chloroplast 858:883 Moreover, C. reinhardtii chloroplast is an attractive platform for expressing malaria antigens because it is capable of folding complex proteins, including those requiring disulfide bond formation, while lacking the ability to glycosylate proteins; a valuable quality of any malaria protein expression system, since the Plasmodium parasite lacks N-linked glycosylation machinery. 29269249 12 52 theme low 1953:1955 arg1 light 1957:1961 low light 1953:1961 low light 1953:1961 However, protein accumulation appears to be favored by cultivating in TAP medium in low light. 29269249 0 53 theme Chlamydomonas 31:43 arg1 reinhardtii 45:55 Chlamydomonas reinhardtii 31:55 Chlamydomonas reinhardtii 31:55 Engineering the chloroplast of Chlamydomonas reinhardtii to express the recombinant PfCelTOS-Il2 antigen-adjuvant fusion protein. 29269249 10 54 theme recombinant 1663:1673 arg1 proteins 1675:1682 expressed recombinant proteins 1653:1682 expressed recombinant proteins 1653:1682 Results demonstrated that expressed recombinant proteins accumulate as a soluble, properly folded and functional protein within algal chloroplasts. 29269249 2 55 theme novel 243:247 arg1 Vaccines 214:221 Vaccines 214:221 Vaccines 214:221 Vaccines are considered as a novel strategy to reduce the burden of malaria. 29269249 2 55 theme novel 243:247 arg1 strategy 249:256 a novel strategy 241:256 a novel strategy to reduce the burden of malaria 241:288 Vaccines are considered as a novel strategy to reduce the burden of malaria. 29269249 6 56 theme beneficial 777:786 arg1 attributes 788:797 beneficial attributes 777:797 beneficial attributes 777:797 Chlamydomonas reinhardtii offers beneficial attributes as oral recombinant protein expression platform. 29269249 8 57 theme oral 1266:1269 arg1 candidate 1279:1287 an oral vaccine candidate 1263:1287 an oral vaccine candidate against malaria 1263:1303 As a first step towards developing an oral vaccine candidate against malaria, here, we expressed a fusion protein consisting of PfCelTOS, a candidate for pre-erythrocytic and transmission-blocking vaccines, fused to human interleukin-2 (IL-2) as vaccine adjuvant in the chloroplast of C. reinhardtii. 29269249 7 58 theme valuable 1099:1106 arg1 it 951:952 it 951:952 it 951:952 Moreover, C. reinhardtii chloroplast is an attractive platform for expressing malaria antigens because it is capable of folding complex proteins, including those requiring disulfide bond formation, while lacking the ability to glycosylate proteins; a valuable quality of any malaria protein expression system, since the Plasmodium parasite lacks N-linked glycosylation machinery. 29269249 7 58 theme valuable 1099:1106 arg1 quality 1108:1114 a valuable quality 1097:1114 a valuable quality of any malaria protein expression system 1097:1155 Moreover, C. reinhardtii chloroplast is an attractive platform for expressing malaria antigens because it is capable of folding complex proteins, including those requiring disulfide bond formation, while lacking the ability to glycosylate proteins; a valuable quality of any malaria protein expression system, since the Plasmodium parasite lacks N-linked glycosylation machinery. 29269249 10 59 theme algal 1755:1759 arg1 chloroplasts 1761:1772 algal chloroplasts 1755:1772 algal chloroplasts 1755:1772 Results demonstrated that expressed recombinant proteins accumulate as a soluble, properly folded and functional protein within algal chloroplasts. 29269249 7 60 theme Plasmodium 1168:1177 arg1 parasite 1179:1186 the Plasmodium parasite 1164:1186 the Plasmodium parasite 1164:1186 Moreover, C. reinhardtii chloroplast is an attractive platform for expressing malaria antigens because it is capable of folding complex proteins, including those requiring disulfide bond formation, while lacking the ability to glycosylate proteins; a valuable quality of any malaria protein expression system, since the Plasmodium parasite lacks N-linked glycosylation machinery. 29269249 3 61 theme complex 314:320 arg1 cycle 327:331 a complex life cycle 312:331 a complex life cycle 312:331 Malaria parasite has a complex life cycle and attempts are being made to develop vaccines that target each stage of the life cycle. 29269249 8 62 theme human 1444:1448 arg1 IL-2 1465:1468 IL-2 1465:1468 IL-2 1465:1468 As a first step towards developing an oral vaccine candidate against malaria, here, we expressed a fusion protein consisting of PfCelTOS, a candidate for pre-erythrocytic and transmission-blocking vaccines, fused to human interleukin-2 (IL-2) as vaccine adjuvant in the chloroplast of C. reinhardtii. 29269249 8 62 theme human 1444:1448 arg1 interleukin-2 1450:1462 human interleukin-2 1444:1462 human interleukin-2 (IL-2) 1444:1469 As a first step towards developing an oral vaccine candidate against malaria, here, we expressed a fusion protein consisting of PfCelTOS, a candidate for pre-erythrocytic and transmission-blocking vaccines, fused to human interleukin-2 (IL-2) as vaccine adjuvant in the chloroplast of C. reinhardtii. 29269249 7 63 gly glycosylate 1075:1085 arg1 proteins 1087:1094 proteins 1087:1094 proteins 1087:1094 Moreover, C. reinhardtii chloroplast is an attractive platform for expressing malaria antigens because it is capable of folding complex proteins, including those requiring disulfide bond formation, while lacking the ability to glycosylate proteins; a valuable quality of any malaria protein expression system, since the Plasmodium parasite lacks N-linked glycosylation machinery. 29269249 9 64 from effect 1533:1538 arg1 production 1582:1591 recombinant protein production 1562:1591 recombinant protein production 1562:1591 The effect of light and media on recombinant protein production and cell growth was then studied. 29269249 9 64 from effect 1533:1538 arg1 growth 1602:1607 cell growth 1597:1607 cell growth 1597:1607 The effect of light and media on recombinant protein production and cell growth was then studied. 29269249 7 65 theme folding 968:974 arg1 proteins 984:991 folding complex proteins 968:991 folding complex proteins 968:991 Moreover, C. reinhardtii chloroplast is an attractive platform for expressing malaria antigens because it is capable of folding complex proteins, including those requiring disulfide bond formation, while lacking the ability to glycosylate proteins; a valuable quality of any malaria protein expression system, since the Plasmodium parasite lacks N-linked glycosylation machinery. 29269249 7 65 theme folding 968:974 arg1 those 1004:1008 those 1004:1008 those 1004:1008 Moreover, C. reinhardtii chloroplast is an attractive platform for expressing malaria antigens because it is capable of folding complex proteins, including those requiring disulfide bond formation, while lacking the ability to glycosylate proteins; a valuable quality of any malaria protein expression system, since the Plasmodium parasite lacks N-linked glycosylation machinery. 29269249 7 66 link N-linked 1194:1201 arg1 machinery 1217:1225 N-linked glycosylation machinery 1194:1225 N-linked glycosylation machinery 1194:1225 Moreover, C. reinhardtii chloroplast is an attractive platform for expressing malaria antigens because it is capable of folding complex proteins, including those requiring disulfide bond formation, while lacking the ability to glycosylate proteins; a valuable quality of any malaria protein expression system, since the Plasmodium parasite lacks N-linked glycosylation machinery. 29269249 6 67 theme Chlamydomonas 744:756 arg1 reinhardtii 758:768 Chlamydomonas reinhardtii 744:768 Chlamydomonas reinhardtii 744:768 Chlamydomonas reinhardtii offers beneficial attributes as oral recombinant protein expression platform. 29269249 1 68 theme infectious 144:153 arg1 disease 155:161 an infectious disease 141:161 an infectious disease having a large negative impact on economic growth 141:211 Malaria is an infectious disease having a large negative impact on economic growth. 29269249 1 68 theme infectious 144:153 arg1 Malaria 130:136 Malaria 130:136 Malaria 130:136 Malaria is an infectious disease having a large negative impact on economic growth. 29269249 8 69 theme pre-erythrocytic 1382:1397 arg1 vaccines 1425:1432 pre-erythrocytic and transmission-blocking vaccines 1382:1432 pre-erythrocytic and transmission-blocking vaccines 1382:1432 As a first step towards developing an oral vaccine candidate against malaria, here, we expressed a fusion protein consisting of PfCelTOS, a candidate for pre-erythrocytic and transmission-blocking vaccines, fused to human interleukin-2 (IL-2) as vaccine adjuvant in the chloroplast of C. reinhardtii. 29269249 4 70 theme Oral 423:426 arg1 vaccines 428:435 Oral vaccines 423:435 Oral vaccines 423:435 Oral vaccines seem to be more feasible to implement in poor countries, since they are relatively inexpensive, needle-free administrated, mostly stable at non-refrigerated conditions and painless. 29269249 7 71 theme bond 1030:1033 arg1 formation 1035:1043 disulfide bond formation 1020:1043 disulfide bond formation 1020:1043 Moreover, C. reinhardtii chloroplast is an attractive platform for expressing malaria antigens because it is capable of folding complex proteins, including those requiring disulfide bond formation, while lacking the ability to glycosylate proteins; a valuable quality of any malaria protein expression system, since the Plasmodium parasite lacks N-linked glycosylation machinery. 29269249 7 72 theme expression 1139:1148 arg1 system 1150:1155 any malaria protein expression system 1119:1155 any malaria protein expression system 1119:1155 Moreover, C. reinhardtii chloroplast is an attractive platform for expressing malaria antigens because it is capable of folding complex proteins, including those requiring disulfide bond formation, while lacking the ability to glycosylate proteins; a valuable quality of any malaria protein expression system, since the Plasmodium parasite lacks N-linked glycosylation machinery. 29269249 4 73 theme non-refrigerated 577:592 arg1 conditions 594:603 non-refrigerated conditions 577:603 non-refrigerated conditions 577:603 Oral vaccines seem to be more feasible to implement in poor countries, since they are relatively inexpensive, needle-free administrated, mostly stable at non-refrigerated conditions and painless. 29269249 0 74 theme recombinant 72:82 arg1 protein 121:127 the recombinant PfCelTOS-Il2 antigen-adjuvant fusion protein 68:127 the recombinant PfCelTOS-Il2 antigen-adjuvant fusion protein 68:127 Engineering the chloroplast of Chlamydomonas reinhardtii to express the recombinant PfCelTOS-Il2 antigen-adjuvant fusion protein. 29269249 10 75 dep soluble 1700:1706 arg1 functional 1729:1738 functional 1729:1738 functional 1729:1738 Results demonstrated that expressed recombinant proteins accumulate as a soluble, properly folded and functional protein within algal chloroplasts. 29269249 10 75 dep soluble 1700:1706 arg1 folded 1718:1723 folded 1718:1723 folded 1718:1723 Results demonstrated that expressed recombinant proteins accumulate as a soluble, properly folded and functional protein within algal chloroplasts. 29269249 7 76 dep capable 957:963 arg1 it 951:952 it 951:952 it 951:952 Moreover, C. reinhardtii chloroplast is an attractive platform for expressing malaria antigens because it is capable of folding complex proteins, including those requiring disulfide bond formation, while lacking the ability to glycosylate proteins; a valuable quality of any malaria protein expression system, since the Plasmodium parasite lacks N-linked glycosylation machinery. 29269249 7 76 dep capable 957:963 arg1 quality 1108:1114 a valuable quality 1097:1114 a valuable quality of any malaria protein expression system 1097:1155 Moreover, C. reinhardtii chloroplast is an attractive platform for expressing malaria antigens because it is capable of folding complex proteins, including those requiring disulfide bond formation, while lacking the ability to glycosylate proteins; a valuable quality of any malaria protein expression system, since the Plasmodium parasite lacks N-linked glycosylation machinery. 29269249 9 77 theme light 1543:1547 arg1 effect 1533:1538 The effect 1529:1538 The effect of light and media on recombinant protein production and cell growth 1529:1607 The effect of light and media on recombinant protein production and cell growth was then studied. 29269249 10 78 theme expressed 1653:1661 arg1 proteins 1675:1682 expressed recombinant proteins 1653:1682 expressed recombinant proteins 1653:1682 Results demonstrated that expressed recombinant proteins accumulate as a soluble, properly folded and functional protein within algal chloroplasts. 29269249 4 79 theme poor 478:481 arg1 countries 483:491 poor countries 478:491 poor countries 478:491 Oral vaccines seem to be more feasible to implement in poor countries, since they are relatively inexpensive, needle-free administrated, mostly stable at non-refrigerated conditions and painless. 29269249 8 80 theme first 1233:1237 arg1 protein 1334:1340 a fusion protein 1325:1340 a fusion protein consisting of PfCelTOS 1325:1363 As a first step towards developing an oral vaccine candidate against malaria, here, we expressed a fusion protein consisting of PfCelTOS, a candidate for pre-erythrocytic and transmission-blocking vaccines, fused to human interleukin-2 (IL-2) as vaccine adjuvant in the chloroplast of C. reinhardtii. 29269249 8 80 theme first 1233:1237 arg1 step 1239:1242 a first step 1231:1242 a first step towards developing an oral vaccine candidate against malaria 1231:1303 As a first step towards developing an oral vaccine candidate against malaria, here, we expressed a fusion protein consisting of PfCelTOS, a candidate for pre-erythrocytic and transmission-blocking vaccines, fused to human interleukin-2 (IL-2) as vaccine adjuvant in the chloroplast of C. reinhardtii. 29269249 1 81 from impact 187:192 arg1 growth 206:211 economic growth 197:211 economic growth 197:211 Malaria is an infectious disease having a large negative impact on economic growth. 29269249 7 82 theme expressing 915:924 arg1 antigens 934:941 expressing malaria antigens 915:941 expressing malaria antigens 915:941 Moreover, C. reinhardtii chloroplast is an attractive platform for expressing malaria antigens because it is capable of folding complex proteins, including those requiring disulfide bond formation, while lacking the ability to glycosylate proteins; a valuable quality of any malaria protein expression system, since the Plasmodium parasite lacks N-linked glycosylation machinery. 29269249 5 83 theme oral 729:732 arg1 vaccines 734:741 oral vaccines 729:741 oral vaccines 729:741 By using recombinant technology, suitable oral hosts could serve as antigen delivering vehicles in developing oral vaccines. 28945362 0 0 theme N-Linked 107:114 arg1 Glycopeptides 116:128 N-Linked Glycopeptides 107:128 N-Linked Glycopeptides 107:128 Glucose-6-Phosphate-Functionalized Magnetic Microsphere as Novel Hydrophilic Probe for Specific Capture of N-Linked Glycopeptides. 28945362 4 1 gly glycopeptides 853:865 arg2 glycopeptides 853:865 glycopeptides 853:865 glycopeptides with high sensitivity (0.5 fmol/μL) and high selectivity (1:100) 853:930 The acquired hydrophilic Fe3O4@G6P microspheres showed superior enrichment performance for glycopeptides with high sensitivity (0.5 fmol/μL) and high selectivity (1:100) and good repeatability (10 times at least). 28945362 4 2 theme good 936:939 arg1 repeatability 941:953 good repeatability 936:953 good repeatability (10 times at least) 936:973 The acquired hydrophilic Fe3O4@G6P microspheres showed superior enrichment performance for glycopeptides with high sensitivity (0.5 fmol/μL) and high selectivity (1:100) and good repeatability (10 times at least). 28945362 2 3 theme plant 436:440 arg1 kingdoms 413:420 the kingdoms 409:420 the kingdoms of animal and plant 409:440 Carbohydrates with outstanding biocompatibility and hydrophilicity are ubiquitous in the kingdoms of animal and plant and could be a wonderful choice as functional groups for glycopeptides enrichment. 28945362 1 4 theme LC-MS/MS 305:312 arg1 analysis 314:321 LC-MS/MS analysis 305:321 LC-MS/MS analysis 305:321 Developing cost-effective approaches based on hydrophilic interaction liquid chromatography (HILIC) has been the main tendency for low-abundance glycopeptides capture before LC-MS/MS analysis. 28945362 5 5 theme G6P 999:1001 arg1 microspheres 1003:1014 the Fe3O4@G6P microspheres 989:1014 the Fe3O4@G6P microspheres 989:1014 Furthermore, the Fe3O4@G6P microspheres also exhibited enrichment ability for glycopeptides in different biosamples. 28945362 1 6 gly glycopeptides 276:288 arg2 glycopeptides 276:288 low-abundance glycopeptides 262:288 low-abundance glycopeptides 262:288 Developing cost-effective approaches based on hydrophilic interaction liquid chromatography (HILIC) has been the main tendency for low-abundance glycopeptides capture before LC-MS/MS analysis. 28945362 3 7 theme indispensable 574:586 arg1 cogs 588:591 the indispensable cogs 570:591 the indispensable cogs in pivotal metabolic wheels of life 570:627 In this work, glucose-6-phosphate, as one of the indispensable cogs in pivotal metabolic wheels of life, was chosen as functionalized groups to be grafted onto the surface of Fe3O4 microspheres via one-step surface fabrication strategy. 28945362 3 8 theme Fe3O4 700:704 arg1 microspheres 706:717 Fe3O4 microspheres 700:717 Fe3O4 microspheres 700:717 In this work, glucose-6-phosphate, as one of the indispensable cogs in pivotal metabolic wheels of life, was chosen as functionalized groups to be grafted onto the surface of Fe3O4 microspheres via one-step surface fabrication strategy. 28945362 3 9 theme cogs 588:591 arg1 one 563:565 one 563:565 one 563:565 In this work, glucose-6-phosphate, as one of the indispensable cogs in pivotal metabolic wheels of life, was chosen as functionalized groups to be grafted onto the surface of Fe3O4 microspheres via one-step surface fabrication strategy. 28945362 3 9 theme cogs 588:591 arg1 cogs 588:591 the indispensable cogs 570:591 the indispensable cogs in pivotal metabolic wheels of life 570:627 In this work, glucose-6-phosphate, as one of the indispensable cogs in pivotal metabolic wheels of life, was chosen as functionalized groups to be grafted onto the surface of Fe3O4 microspheres via one-step surface fabrication strategy. 28945362 6 10 theme serum 1252:1256 arg1 μL 1246:1247 merely 2 μL 1237:1247 merely 2 μL of serum and saliva 1237:1267 A total of 243 glycopeptides assigned to 92 glycoproteins and 183 glycopeptides corresponding to 74 different glycoproteins was identified from merely 2 μL of serum and saliva, respectively. 28945362 2 11 from ubiquitous 395:404 arg1 kingdoms 413:420 the kingdoms 409:420 the kingdoms of animal and plant 409:440 Carbohydrates with outstanding biocompatibility and hydrophilicity are ubiquitous in the kingdoms of animal and plant and could be a wonderful choice as functional groups for glycopeptides enrichment. 28945362 0 12 theme Glycopeptides 116:128 arg1 Capture 96:102 Specific Capture 87:102 Specific Capture of N-Linked Glycopeptides 87:128 Glucose-6-Phosphate-Functionalized Magnetic Microsphere as Novel Hydrophilic Probe for Specific Capture of N-Linked Glycopeptides. 28945362 3 13 from cogs 588:591 arg1 wheels 614:619 pivotal metabolic wheels 596:619 pivotal metabolic wheels of life 596:627 In this work, glucose-6-phosphate, as one of the indispensable cogs in pivotal metabolic wheels of life, was chosen as functionalized groups to be grafted onto the surface of Fe3O4 microspheres via one-step surface fabrication strategy. 28945362 4 14 theme acquired 766:773 arg1 microspheres 797:808 The acquired hydrophilic Fe3O4@G6P microspheres 762:808 The acquired hydrophilic Fe3O4@G6P microspheres 762:808 The acquired hydrophilic Fe3O4@G6P microspheres showed superior enrichment performance for glycopeptides with high sensitivity (0.5 fmol/μL) and high selectivity (1:100) and good repeatability (10 times at least). 28945362 4 15 theme @ 792:792 arg1 microspheres 797:808 The acquired hydrophilic Fe3O4@G6P microspheres 762:808 The acquired hydrophilic Fe3O4@G6P microspheres 762:808 The acquired hydrophilic Fe3O4@G6P microspheres showed superior enrichment performance for glycopeptides with high sensitivity (0.5 fmol/μL) and high selectivity (1:100) and good repeatability (10 times at least). 28945362 4 16 theme Fe3O4 787:791 arg1 microspheres 797:808 The acquired hydrophilic Fe3O4@G6P microspheres 762:808 The acquired hydrophilic Fe3O4@G6P microspheres 762:808 The acquired hydrophilic Fe3O4@G6P microspheres showed superior enrichment performance for glycopeptides with high sensitivity (0.5 fmol/μL) and high selectivity (1:100) and good repeatability (10 times at least). 28945362 2 17 theme outstanding 343:353 arg1 biocompatibility 355:370 outstanding biocompatibility 343:370 outstanding biocompatibility 343:370 Carbohydrates with outstanding biocompatibility and hydrophilicity are ubiquitous in the kingdoms of animal and plant and could be a wonderful choice as functional groups for glycopeptides enrichment. 28945362 6 18 gly glycoproteins 1203:1215 arg1 glycoproteins 1203:1215 74 different glycoproteins 1190:1215 74 different glycoproteins 1190:1215 A total of 243 glycopeptides assigned to 92 glycoproteins and 183 glycopeptides corresponding to 74 different glycoproteins was identified from merely 2 μL of serum and saliva, respectively. 28945362 3 19 theme metabolic 604:612 arg1 wheels 614:619 pivotal metabolic wheels 596:619 pivotal metabolic wheels of life 596:627 In this work, glucose-6-phosphate, as one of the indispensable cogs in pivotal metabolic wheels of life, was chosen as functionalized groups to be grafted onto the surface of Fe3O4 microspheres via one-step surface fabrication strategy. 28945362 2 20 theme wonderful 457:465 arg1 choice 467:472 a wonderful choice 455:472 a wonderful choice as functional groups for glycopeptides enrichment 455:522 Carbohydrates with outstanding biocompatibility and hydrophilicity are ubiquitous in the kingdoms of animal and plant and could be a wonderful choice as functional groups for glycopeptides enrichment. 28945362 0 21 theme Magnetic 35:42 arg1 Microsphere 44:54 Magnetic Microsphere 35:54 Magnetic Microsphere 35:54 Glucose-6-Phosphate-Functionalized Magnetic Microsphere as Novel Hydrophilic Probe for Specific Capture of N-Linked Glycopeptides. 28945362 5 22 theme @ 998:998 arg1 microspheres 1003:1014 the Fe3O4@G6P microspheres 989:1014 the Fe3O4@G6P microspheres 989:1014 Furthermore, the Fe3O4@G6P microspheres also exhibited enrichment ability for glycopeptides in different biosamples. 28945362 6 23 theme saliva 1262:1267 arg1 μL 1246:1247 merely 2 μL 1237:1247 merely 2 μL of serum and saliva 1237:1267 A total of 243 glycopeptides assigned to 92 glycoproteins and 183 glycopeptides corresponding to 74 different glycoproteins was identified from merely 2 μL of serum and saliva, respectively. 28945362 5 24 theme Fe3O4 993:997 arg1 microspheres 1003:1014 the Fe3O4@G6P microspheres 989:1014 the Fe3O4@G6P microspheres 989:1014 Furthermore, the Fe3O4@G6P microspheres also exhibited enrichment ability for glycopeptides in different biosamples. 28945362 4 25 with glycopeptides 853:865 arg1 1:100 925:929 1:100 925:929 1:100 925:929 The acquired hydrophilic Fe3O4@G6P microspheres showed superior enrichment performance for glycopeptides with high sensitivity (0.5 fmol/μL) and high selectivity (1:100) and good repeatability (10 times at least). 28945362 4 25 with glycopeptides 853:865 arg1 selectivity 912:922 high selectivity 907:922 high selectivity (1:100) 907:930 The acquired hydrophilic Fe3O4@G6P microspheres showed superior enrichment performance for glycopeptides with high sensitivity (0.5 fmol/μL) and high selectivity (1:100) and good repeatability (10 times at least). 28945362 4 25 with glycopeptides 853:865 arg1 sensitivity 877:887 high sensitivity 872:887 high sensitivity (0.5 fmol/μL) 872:901 The acquired hydrophilic Fe3O4@G6P microspheres showed superior enrichment performance for glycopeptides with high sensitivity (0.5 fmol/μL) and high selectivity (1:100) and good repeatability (10 times at least). 28945362 4 25 with glycopeptides 853:865 arg1 fmol/μL 894:900 0.5 fmol/μL 890:900 0.5 fmol/μL 890:900 The acquired hydrophilic Fe3O4@G6P microspheres showed superior enrichment performance for glycopeptides with high sensitivity (0.5 fmol/μL) and high selectivity (1:100) and good repeatability (10 times at least). 28945362 6 26 gly glycopeptides 1159:1171 arg2 glycopeptides 1159:1171 183 glycopeptides 1155:1171 183 glycopeptides 1155:1171 A total of 243 glycopeptides assigned to 92 glycoproteins and 183 glycopeptides corresponding to 74 different glycoproteins was identified from merely 2 μL of serum and saliva, respectively. 28945362 3 27 theme life 624:627 arg1 wheels 614:619 pivotal metabolic wheels 596:619 pivotal metabolic wheels of life 596:627 In this work, glucose-6-phosphate, as one of the indispensable cogs in pivotal metabolic wheels of life, was chosen as functionalized groups to be grafted onto the surface of Fe3O4 microspheres via one-step surface fabrication strategy. 28945362 2 28 from kingdoms 413:420 arg1 ubiquitous 395:404 ubiquitous 395:404 ubiquitous 395:404 Carbohydrates with outstanding biocompatibility and hydrophilicity are ubiquitous in the kingdoms of animal and plant and could be a wonderful choice as functional groups for glycopeptides enrichment. 28945362 6 29 theme glycopeptides 1108:1120 arg1 total 1095:1099 A total 1093:1099 A total of 243 glycopeptides assigned to 92 glycoproteins and 183 glycopeptides corresponding to 74 different glycoproteins 1093:1215 A total of 243 glycopeptides assigned to 92 glycoproteins and 183 glycopeptides corresponding to 74 different glycoproteins was identified from merely 2 μL of serum and saliva, respectively. 28945362 2 30 theme glycopeptides 499:511 arg1 enrichment 513:522 glycopeptides enrichment 499:522 glycopeptides enrichment 499:522 Carbohydrates with outstanding biocompatibility and hydrophilicity are ubiquitous in the kingdoms of animal and plant and could be a wonderful choice as functional groups for glycopeptides enrichment. 28945362 3 31 theme pivotal 596:602 arg1 wheels 614:619 pivotal metabolic wheels 596:619 pivotal metabolic wheels of life 596:627 In this work, glucose-6-phosphate, as one of the indispensable cogs in pivotal metabolic wheels of life, was chosen as functionalized groups to be grafted onto the surface of Fe3O4 microspheres via one-step surface fabrication strategy. 28945362 1 32 dep capture 290:296 arg1 analysis 314:321 LC-MS/MS analysis 305:321 LC-MS/MS analysis 305:321 Developing cost-effective approaches based on hydrophilic interaction liquid chromatography (HILIC) has been the main tendency for low-abundance glycopeptides capture before LC-MS/MS analysis. 28945362 1 33 theme cost-effective 142:155 arg1 approaches 157:166 cost-effective approaches 142:166 cost-effective approaches based on hydrophilic interaction liquid chromatography (HILIC) 142:229 Developing cost-effective approaches based on hydrophilic interaction liquid chromatography (HILIC) has been the main tendency for low-abundance glycopeptides capture before LC-MS/MS analysis. 28945362 1 34 theme main 244:247 arg1 tendency 249:256 the main tendency 240:256 the main tendency for low-abundance glycopeptides 240:288 Developing cost-effective approaches based on hydrophilic interaction liquid chromatography (HILIC) has been the main tendency for low-abundance glycopeptides capture before LC-MS/MS analysis. 28945362 0 35 theme Hydrophilic 65:75 arg1 Probe 77:81 Novel Hydrophilic Probe 59:81 Novel Hydrophilic Probe for Specific Capture of N-Linked Glycopeptides 59:128 Glucose-6-Phosphate-Functionalized Magnetic Microsphere as Novel Hydrophilic Probe for Specific Capture of N-Linked Glycopeptides. 28945362 6 36 theme different 1193:1201 arg1 glycoproteins 1203:1215 74 different glycoproteins 1190:1215 74 different glycoproteins 1190:1215 A total of 243 glycopeptides assigned to 92 glycoproteins and 183 glycopeptides corresponding to 74 different glycoproteins was identified from merely 2 μL of serum and saliva, respectively. 28945362 3 37 theme microspheres 706:717 arg1 surface 689:695 the surface 685:695 the surface of Fe3O4 microspheres 685:717 In this work, glucose-6-phosphate, as one of the indispensable cogs in pivotal metabolic wheels of life, was chosen as functionalized groups to be grafted onto the surface of Fe3O4 microspheres via one-step surface fabrication strategy. 28945362 5 38 theme different 1071:1079 arg1 biosamples 1081:1090 different biosamples 1071:1090 different biosamples 1071:1090 Furthermore, the Fe3O4@G6P microspheres also exhibited enrichment ability for glycopeptides in different biosamples. 28945362 2 39 theme functional 477:486 arg1 groups 488:493 functional groups 477:493 functional groups for glycopeptides enrichment 477:522 Carbohydrates with outstanding biocompatibility and hydrophilicity are ubiquitous in the kingdoms of animal and plant and could be a wonderful choice as functional groups for glycopeptides enrichment. 28945362 0 40 theme Novel 59:63 arg1 Probe 77:81 Novel Hydrophilic Probe 59:81 Novel Hydrophilic Probe for Specific Capture of N-Linked Glycopeptides 59:128 Glucose-6-Phosphate-Functionalized Magnetic Microsphere as Novel Hydrophilic Probe for Specific Capture of N-Linked Glycopeptides. 28945362 4 41 dep repeatability 941:953 arg1 times 959:963 10 times 956:963 10 times at least 956:972 The acquired hydrophilic Fe3O4@G6P microspheres showed superior enrichment performance for glycopeptides with high sensitivity (0.5 fmol/μL) and high selectivity (1:100) and good repeatability (10 times at least). 28945362 4 42 theme high 907:910 arg1 1:100 925:929 1:100 925:929 1:100 925:929 The acquired hydrophilic Fe3O4@G6P microspheres showed superior enrichment performance for glycopeptides with high sensitivity (0.5 fmol/μL) and high selectivity (1:100) and good repeatability (10 times at least). 28945362 4 42 theme high 907:910 arg1 selectivity 912:922 high selectivity 907:922 high selectivity (1:100) 907:930 The acquired hydrophilic Fe3O4@G6P microspheres showed superior enrichment performance for glycopeptides with high sensitivity (0.5 fmol/μL) and high selectivity (1:100) and good repeatability (10 times at least). 28945362 2 43 theme animal 425:430 arg1 kingdoms 413:420 the kingdoms 409:420 the kingdoms of animal and plant 409:440 Carbohydrates with outstanding biocompatibility and hydrophilicity are ubiquitous in the kingdoms of animal and plant and could be a wonderful choice as functional groups for glycopeptides enrichment. 28945362 5 44 gly glycopeptides 1054:1066 arg2 glycopeptides 1054:1066 glycopeptides 1054:1066 glycopeptides 1054:1066 Furthermore, the Fe3O4@G6P microspheres also exhibited enrichment ability for glycopeptides in different biosamples. 28945362 2 45 with Carbohydrates 324:336 arg1 biocompatibility 355:370 outstanding biocompatibility 343:370 outstanding biocompatibility 343:370 Carbohydrates with outstanding biocompatibility and hydrophilicity are ubiquitous in the kingdoms of animal and plant and could be a wonderful choice as functional groups for glycopeptides enrichment. 28945362 2 45 with Carbohydrates 324:336 arg1 hydrophilicity 376:389 hydrophilicity 376:389 hydrophilicity 376:389 Carbohydrates with outstanding biocompatibility and hydrophilicity are ubiquitous in the kingdoms of animal and plant and could be a wonderful choice as functional groups for glycopeptides enrichment. 28945362 6 46 gly glycoproteins 1137:1149 arg1 glycoproteins 1137:1149 92 glycoproteins 1134:1149 92 glycoproteins 1134:1149 A total of 243 glycopeptides assigned to 92 glycoproteins and 183 glycopeptides corresponding to 74 different glycoproteins was identified from merely 2 μL of serum and saliva, respectively. 28945362 3 47 theme surface 732:738 arg1 strategy 752:759 one-step surface fabrication strategy 723:759 one-step surface fabrication strategy 723:759 In this work, glucose-6-phosphate, as one of the indispensable cogs in pivotal metabolic wheels of life, was chosen as functionalized groups to be grafted onto the surface of Fe3O4 microspheres via one-step surface fabrication strategy. 28945362 3 48 theme functionalized 644:657 arg1 groups 659:664 functionalized groups 644:664 functionalized groups 644:664 In this work, glucose-6-phosphate, as one of the indispensable cogs in pivotal metabolic wheels of life, was chosen as functionalized groups to be grafted onto the surface of Fe3O4 microspheres via one-step surface fabrication strategy. 28945362 3 48 theme functionalized 644:657 arg1 glucose-6-phosphate 539:557 glucose-6-phosphate 539:557 glucose-6-phosphate 539:557 In this work, glucose-6-phosphate, as one of the indispensable cogs in pivotal metabolic wheels of life, was chosen as functionalized groups to be grafted onto the surface of Fe3O4 microspheres via one-step surface fabrication strategy. 28945362 4 49 theme hydrophilic 775:785 arg1 microspheres 797:808 The acquired hydrophilic Fe3O4@G6P microspheres 762:808 The acquired hydrophilic Fe3O4@G6P microspheres 762:808 The acquired hydrophilic Fe3O4@G6P microspheres showed superior enrichment performance for glycopeptides with high sensitivity (0.5 fmol/μL) and high selectivity (1:100) and good repeatability (10 times at least). 28945362 6 50 gly glycopeptides 1108:1120 arg2 glycopeptides 1108:1120 243 glycopeptides 1104:1120 243 glycopeptides assigned to 92 glycoproteins and 183 glycopeptides 1104:1171 A total of 243 glycopeptides assigned to 92 glycoproteins and 183 glycopeptides corresponding to 74 different glycoproteins was identified from merely 2 μL of serum and saliva, respectively. 28945362 3 51 theme fabrication 740:750 arg1 strategy 752:759 one-step surface fabrication strategy 723:759 one-step surface fabrication strategy 723:759 In this work, glucose-6-phosphate, as one of the indispensable cogs in pivotal metabolic wheels of life, was chosen as functionalized groups to be grafted onto the surface of Fe3O4 microspheres via one-step surface fabrication strategy. 28945362 4 52 theme G6P 793:795 arg1 microspheres 797:808 The acquired hydrophilic Fe3O4@G6P microspheres 762:808 The acquired hydrophilic Fe3O4@G6P microspheres 762:808 The acquired hydrophilic Fe3O4@G6P microspheres showed superior enrichment performance for glycopeptides with high sensitivity (0.5 fmol/μL) and high selectivity (1:100) and good repeatability (10 times at least). 28945362 4 53 theme enrichment 826:835 arg1 performance 837:847 superior enrichment performance 817:847 superior enrichment performance for glycopeptides with high sensitivity (0.5 fmol/μL) and high selectivity (1:100) 817:930 The acquired hydrophilic Fe3O4@G6P microspheres showed superior enrichment performance for glycopeptides with high sensitivity (0.5 fmol/μL) and high selectivity (1:100) and good repeatability (10 times at least). 28945362 1 54 theme low-abundance 262:274 arg1 glycopeptides 276:288 low-abundance glycopeptides 262:288 low-abundance glycopeptides 262:288 Developing cost-effective approaches based on hydrophilic interaction liquid chromatography (HILIC) has been the main tendency for low-abundance glycopeptides capture before LC-MS/MS analysis. 28945362 5 55 theme enrichment 1031:1040 arg1 ability 1042:1048 enrichment ability 1031:1048 enrichment ability for glycopeptides 1031:1066 Furthermore, the Fe3O4@G6P microspheres also exhibited enrichment ability for glycopeptides in different biosamples. 28945362 4 56 theme high 872:875 arg1 sensitivity 877:887 high sensitivity 872:887 high sensitivity (0.5 fmol/μL) 872:901 The acquired hydrophilic Fe3O4@G6P microspheres showed superior enrichment performance for glycopeptides with high sensitivity (0.5 fmol/μL) and high selectivity (1:100) and good repeatability (10 times at least). 28945362 4 56 theme high 872:875 arg1 fmol/μL 894:900 0.5 fmol/μL 890:900 0.5 fmol/μL 890:900 The acquired hydrophilic Fe3O4@G6P microspheres showed superior enrichment performance for glycopeptides with high sensitivity (0.5 fmol/μL) and high selectivity (1:100) and good repeatability (10 times at least). 28945362 4 57 theme superior 817:824 arg1 performance 837:847 superior enrichment performance 817:847 superior enrichment performance for glycopeptides with high sensitivity (0.5 fmol/μL) and high selectivity (1:100) 817:930 The acquired hydrophilic Fe3O4@G6P microspheres showed superior enrichment performance for glycopeptides with high sensitivity (0.5 fmol/μL) and high selectivity (1:100) and good repeatability (10 times at least). 28945362 1 58 theme hydrophilic 177:187 arg1 HILIC 224:228 HILIC 224:228 HILIC 224:228 Developing cost-effective approaches based on hydrophilic interaction liquid chromatography (HILIC) has been the main tendency for low-abundance glycopeptides capture before LC-MS/MS analysis. 28945362 1 58 theme hydrophilic 177:187 arg1 chromatography 208:221 hydrophilic interaction liquid chromatography 177:221 hydrophilic interaction liquid chromatography (HILIC) 177:229 Developing cost-effective approaches based on hydrophilic interaction liquid chromatography (HILIC) has been the main tendency for low-abundance glycopeptides capture before LC-MS/MS analysis. 28945362 3 59 theme one-step 723:730 arg1 strategy 752:759 one-step surface fabrication strategy 723:759 one-step surface fabrication strategy 723:759 In this work, glucose-6-phosphate, as one of the indispensable cogs in pivotal metabolic wheels of life, was chosen as functionalized groups to be grafted onto the surface of Fe3O4 microspheres via one-step surface fabrication strategy. 28945362 2 60 gly glycopeptides 499:511 arg2 glycopeptides 499:511 glycopeptides enrichment 499:522 glycopeptides enrichment 499:522 Carbohydrates with outstanding biocompatibility and hydrophilicity are ubiquitous in the kingdoms of animal and plant and could be a wonderful choice as functional groups for glycopeptides enrichment. 28945362 1 61 theme interaction 189:199 arg1 HILIC 224:228 HILIC 224:228 HILIC 224:228 Developing cost-effective approaches based on hydrophilic interaction liquid chromatography (HILIC) has been the main tendency for low-abundance glycopeptides capture before LC-MS/MS analysis. 28945362 1 61 theme interaction 189:199 arg1 chromatography 208:221 hydrophilic interaction liquid chromatography 177:221 hydrophilic interaction liquid chromatography (HILIC) 177:229 Developing cost-effective approaches based on hydrophilic interaction liquid chromatography (HILIC) has been the main tendency for low-abundance glycopeptides capture before LC-MS/MS analysis. 28945362 0 62 theme Specific 87:94 arg1 Capture 96:102 Specific Capture 87:102 Specific Capture of N-Linked Glycopeptides 87:128 Glucose-6-Phosphate-Functionalized Magnetic Microsphere as Novel Hydrophilic Probe for Specific Capture of N-Linked Glycopeptides. 28945362 1 63 theme liquid 201:206 arg1 HILIC 224:228 HILIC 224:228 HILIC 224:228 Developing cost-effective approaches based on hydrophilic interaction liquid chromatography (HILIC) has been the main tendency for low-abundance glycopeptides capture before LC-MS/MS analysis. 28945362 1 63 theme liquid 201:206 arg1 chromatography 208:221 hydrophilic interaction liquid chromatography 177:221 hydrophilic interaction liquid chromatography (HILIC) 177:229 Developing cost-effective approaches based on hydrophilic interaction liquid chromatography (HILIC) has been the main tendency for low-abundance glycopeptides capture before LC-MS/MS analysis. 27160519 2 0 theme important 516:524 arg1 information 526:536 important information 516:536 important information for process design and control 516:567 Therefore, identification and detailed characterization of Fc glycan critical quality attributes (CQAs) provides important information for process design and control. 27160519 0 1 from effect 19:24 arg1 activity 115:122 FcγRIIIa receptor binding activity 89:122 FcγRIIIa receptor binding activity 89:122 Characterizing the effect of multiple Fc glycan attributes on the effector functions and FcγRIIIa receptor binding activity of an IgG1 antibody. 27160519 0 1 from effect 19:24 arg1 functions 75:83 effector functions 66:83 effector functions 66:83 Characterizing the effect of multiple Fc glycan attributes on the effector functions and FcγRIIIa receptor binding activity of an IgG1 antibody. 27160519 9 2 theme characterization 1419:1434 arg1 type 1404:1407 This type 1399:1407 This type of glycan characterization and modeling 1399:1447 This type of glycan characterization and modeling can provide valuable information for development, manufacturing support and process improvements for IgG products that require effector function for efficacy. 27160519 5 3 theme experiment 855:864 arg1 design 845:850 a full-factorial design 828:850 a full-factorial design of experiment (DOE) 828:870 Next, a full-factorial design of experiment (DOE) to characterize the possible interactions and relative effect of these three glycan species on ADCC, CDC, and FcγRIIIa binding was employed. 27160519 1 4 theme N-linked 145:152 arg1 glycosylation 157:169 N-linked Fc glycosylation 145:169 N-linked Fc glycosylation of IgG1 monoclonal antibody therapeutics 145:210 N-linked Fc glycosylation of IgG1 monoclonal antibody therapeutics can directly influence their mechanism of action by impacting IgG effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). 27160519 1 5 theme action 254:259 arg1 mechanism 241:249 their mechanism 235:249 their mechanism of action 235:259 N-linked Fc glycosylation of IgG1 monoclonal antibody therapeutics can directly influence their mechanism of action by impacting IgG effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). 27160519 0 6 theme effector 66:73 arg1 functions 75:83 effector functions 66:83 effector functions 66:83 Characterizing the effect of multiple Fc glycan attributes on the effector functions and FcγRIIIa receptor binding activity of an IgG1 antibody. 27160519 1 7 gly glycosylation 157:169 arg1 therapeutics 199:210 IgG1 monoclonal antibody therapeutics 174:210 IgG1 monoclonal antibody therapeutics 174:210 N-linked Fc glycosylation of IgG1 monoclonal antibody therapeutics can directly influence their mechanism of action by impacting IgG effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). 27160519 1 8 theme Fc 154:155 arg1 glycosylation 157:169 N-linked Fc glycosylation 145:169 N-linked Fc glycosylation of IgG1 monoclonal antibody therapeutics 145:210 N-linked Fc glycosylation of IgG1 monoclonal antibody therapeutics can directly influence their mechanism of action by impacting IgG effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). 27160519 5 9 theme species 956:962 arg1 effect 927:932 relative effect 918:932 relative effect of these three glycan species on ADCC, CDC, and FcγRIIIa binding 918:997 Next, a full-factorial design of experiment (DOE) to characterize the possible interactions and relative effect of these three glycan species on ADCC, CDC, and FcγRIIIa binding was employed. 27160519 0 10 theme FcγRIIIa 89:96 arg1 activity 115:122 FcγRIIIa receptor binding activity 89:122 FcγRIIIa receptor binding activity 89:122 Characterizing the effect of multiple Fc glycan attributes on the effector functions and FcγRIIIa receptor binding activity of an IgG1 antibody. 27160519 1 11 theme complement-dependent 362:381 arg1 CDC 397:399 CDC 397:399 CDC 397:399 N-linked Fc glycosylation of IgG1 monoclonal antibody therapeutics can directly influence their mechanism of action by impacting IgG effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). 27160519 1 11 theme complement-dependent 362:381 arg1 cytotoxicity 383:394 complement-dependent cytotoxicity 362:394 complement-dependent cytotoxicity (CDC) 362:400 N-linked Fc glycosylation of IgG1 monoclonal antibody therapeutics can directly influence their mechanism of action by impacting IgG effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). 27160519 5 12 from effect 927:932 arg1 ADCC 967:970 ADCC 967:970 ADCC 967:970 Next, a full-factorial design of experiment (DOE) to characterize the possible interactions and relative effect of these three glycan species on ADCC, CDC, and FcγRIIIa binding was employed. 27160519 5 12 from effect 927:932 arg1 binding 991:997 FcγRIIIa binding 982:997 FcγRIIIa binding 982:997 Next, a full-factorial design of experiment (DOE) to characterize the possible interactions and relative effect of these three glycan species on ADCC, CDC, and FcγRIIIa binding was employed. 27160519 5 12 from effect 927:932 arg1 CDC 973:975 CDC 973:975 CDC 973:975 Next, a full-factorial design of experiment (DOE) to characterize the possible interactions and relative effect of these three glycan species on ADCC, CDC, and FcγRIIIa binding was employed. 27160519 3 13 theme two-step 572:579 arg1 approach 581:588 A two-step approach 570:588 A two-step approach 570:588 A two-step approach was used to identify and characterize the Fc glycan CQAs for an IgG1 Mab with effector function. 27160519 4 14 theme quality 763:769 arg1 attributes 771:780 glycan critical quality attributes 747:780 glycan critical quality attributes that influence ADCC and CDC activities 747:819 First, single factor experiments were performed to identify glycan critical quality attributes that influence ADCC and CDC activities. 27160519 6 15 theme configuration 1122:1134 arg1 CDC 1085:1087 CDC 1085:1087 CDC 1085:1087 Additionally, the DOE data were used to develop models to predict ADCC, CDC, and FcγRIIIa binding of a given configuration of the three glycan species for this IgG1 molecule. 27160519 6 15 theme configuration 1122:1134 arg1 ADCC 1079:1082 ADCC 1079:1082 ADCC 1079:1082 Additionally, the DOE data were used to develop models to predict ADCC, CDC, and FcγRIIIa binding of a given configuration of the three glycan species for this IgG1 molecule. 27160519 6 15 theme configuration 1122:1134 arg1 binding 1103:1109 FcγRIIIa binding 1094:1109 FcγRIIIa binding 1094:1109 Additionally, the DOE data were used to develop models to predict ADCC, CDC, and FcγRIIIa binding of a given configuration of the three glycan species for this IgG1 molecule. 27160519 6 16 theme glycan 1149:1154 arg1 species 1156:1162 the three glycan species 1139:1162 the three glycan species 1139:1162 Additionally, the DOE data were used to develop models to predict ADCC, CDC, and FcγRIIIa binding of a given configuration of the three glycan species for this IgG1 molecule. 27160519 6 17 used used 1045:1048 arg2 data 1035:1038 the DOE data 1027:1038 the DOE data 1027:1038 Additionally, the DOE data were used to develop models to predict ADCC, CDC, and FcγRIIIa binding of a given configuration of the three glycan species for this IgG1 molecule. 27160519 5 18 theme relative 918:925 arg1 effect 927:932 relative effect 918:932 relative effect of these three glycan species on ADCC, CDC, and FcγRIIIa binding 918:997 Next, a full-factorial design of experiment (DOE) to characterize the possible interactions and relative effect of these three glycan species on ADCC, CDC, and FcγRIIIa binding was employed. 27160519 1 19 theme IgG 274:276 arg1 cytotoxicity 338:349 antibody-dependent cell-mediated cytotoxicity 305:349 antibody-dependent cell-mediated cytotoxicity (ADCC) 305:356 N-linked Fc glycosylation of IgG1 monoclonal antibody therapeutics can directly influence their mechanism of action by impacting IgG effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). 27160519 1 19 theme IgG 274:276 arg1 functions 287:295 IgG effector functions 274:295 IgG effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) 274:400 N-linked Fc glycosylation of IgG1 monoclonal antibody therapeutics can directly influence their mechanism of action by impacting IgG effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). 27160519 1 19 theme IgG 274:276 arg1 cytotoxicity 383:394 complement-dependent cytotoxicity 362:394 complement-dependent cytotoxicity (CDC) 362:400 N-linked Fc glycosylation of IgG1 monoclonal antibody therapeutics can directly influence their mechanism of action by impacting IgG effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). 27160519 0 20 theme binding 107:113 arg1 activity 115:122 FcγRIIIa receptor binding activity 89:122 FcγRIIIa receptor binding activity 89:122 Characterizing the effect of multiple Fc glycan attributes on the effector functions and FcγRIIIa receptor binding activity of an IgG1 antibody. 27160519 4 21 theme CDC 806:808 arg1 activities 810:819 ADCC and CDC activities 797:819 ADCC and CDC activities 797:819 First, single factor experiments were performed to identify glycan critical quality attributes that influence ADCC and CDC activities. 27160519 6 22 theme IgG1 1173:1176 arg1 molecule 1178:1185 this IgG1 molecule 1168:1185 this IgG1 molecule 1168:1185 Additionally, the DOE data were used to develop models to predict ADCC, CDC, and FcγRIIIa binding of a given configuration of the three glycan species for this IgG1 molecule. 27160519 0 23 theme receptor 98:105 arg1 activity 115:122 FcγRIIIa receptor binding activity 89:122 FcγRIIIa receptor binding activity 89:122 Characterizing the effect of multiple Fc glycan attributes on the effector functions and FcγRIIIa receptor binding activity of an IgG1 antibody. 27160519 10 24 theme Chemical 1637:1644 arg1 Engineers 1646:1654 Chemical Engineers 1637:1654 Chemical Engineers 1637:1654 © 2016 American Institute of Chemical Engineers Biotechnol. 27160519 5 25 theme FcγRIIIa 982:989 arg1 binding 991:997 FcγRIIIa binding 982:997 FcγRIIIa binding 982:997 Next, a full-factorial design of experiment (DOE) to characterize the possible interactions and relative effect of these three glycan species on ADCC, CDC, and FcγRIIIa binding was employed. 27160519 2 26 theme quality 481:487 arg1 CQAs 501:504 CQAs 501:504 CQAs 501:504 Therefore, identification and detailed characterization of Fc glycan critical quality attributes (CQAs) provides important information for process design and control. 27160519 2 26 theme quality 481:487 arg1 attributes 489:498 Fc glycan critical quality attributes 462:498 Fc glycan critical quality attributes (CQAs) 462:505 Therefore, identification and detailed characterization of Fc glycan critical quality attributes (CQAs) provides important information for process design and control. 27160519 7 27 contain has 1241:1243 arg1 mono/bi 1233:1239 afuco mono/bi 1227:1239 afuco mono/bi 1227:1239 The results demonstrate that for ADCC, afuco mono/bi has the largest effect, followed by HM and β-gal, while FcγRIIIa binding is affected by afuco mono/bi and β-gal. 27160519 7 27 contain has 1241:1243 arg2 effect 1257:1262 the largest effect 1245:1262 the largest effect 1245:1262 The results demonstrate that for ADCC, afuco mono/bi has the largest effect, followed by HM and β-gal, while FcγRIIIa binding is affected by afuco mono/bi and β-gal. 27160519 7 28 theme largest 1249:1255 arg1 effect 1257:1262 the largest effect 1245:1262 the largest effect 1245:1262 The results demonstrate that for ADCC, afuco mono/bi has the largest effect, followed by HM and β-gal, while FcγRIIIa binding is affected by afuco mono/bi and β-gal. 27160519 0 29 dep functions 75:83 arg1 the 62:64 the 62:64 the 62:64 Characterizing the effect of multiple Fc glycan attributes on the effector functions and FcγRIIIa receptor binding activity of an IgG1 antibody. 27160519 1 30 theme IgG1 174:177 arg1 therapeutics 199:210 IgG1 monoclonal antibody therapeutics 174:210 IgG1 monoclonal antibody therapeutics 174:210 N-linked Fc glycosylation of IgG1 monoclonal antibody therapeutics can directly influence their mechanism of action by impacting IgG effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). 27160519 2 31 theme critical 472:479 arg1 CQAs 501:504 CQAs 501:504 CQAs 501:504 Therefore, identification and detailed characterization of Fc glycan critical quality attributes (CQAs) provides important information for process design and control. 27160519 2 31 theme critical 472:479 arg1 attributes 489:498 Fc glycan critical quality attributes 462:498 Fc glycan critical quality attributes (CQAs) 462:505 Therefore, identification and detailed characterization of Fc glycan critical quality attributes (CQAs) provides important information for process design and control. 27160519 1 32 theme effector 278:285 arg1 cytotoxicity 338:349 antibody-dependent cell-mediated cytotoxicity 305:349 antibody-dependent cell-mediated cytotoxicity (ADCC) 305:356 N-linked Fc glycosylation of IgG1 monoclonal antibody therapeutics can directly influence their mechanism of action by impacting IgG effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). 27160519 1 32 theme effector 278:285 arg1 functions 287:295 IgG effector functions 274:295 IgG effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) 274:400 N-linked Fc glycosylation of IgG1 monoclonal antibody therapeutics can directly influence their mechanism of action by impacting IgG effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). 27160519 1 32 theme effector 278:285 arg1 cytotoxicity 383:394 complement-dependent cytotoxicity 362:394 complement-dependent cytotoxicity (CDC) 362:400 N-linked Fc glycosylation of IgG1 monoclonal antibody therapeutics can directly influence their mechanism of action by impacting IgG effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). 27160519 4 33 theme critical 754:761 arg1 attributes 771:780 glycan critical quality attributes 747:780 glycan critical quality attributes that influence ADCC and CDC activities 747:819 First, single factor experiments were performed to identify glycan critical quality attributes that influence ADCC and CDC activities. 27160519 9 34 theme glycan 1412:1417 arg1 characterization 1419:1434 glycan characterization 1412:1434 glycan characterization 1412:1434 This type of glycan characterization and modeling can provide valuable information for development, manufacturing support and process improvements for IgG products that require effector function for efficacy. 27160519 1 35 theme monoclonal 179:188 arg1 therapeutics 199:210 IgG1 monoclonal antibody therapeutics 174:210 IgG1 monoclonal antibody therapeutics 174:210 N-linked Fc glycosylation of IgG1 monoclonal antibody therapeutics can directly influence their mechanism of action by impacting IgG effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). 27160519 2 36 theme glycan 465:470 arg1 CQAs 501:504 CQAs 501:504 CQAs 501:504 Therefore, identification and detailed characterization of Fc glycan critical quality attributes (CQAs) provides important information for process design and control. 27160519 2 36 theme glycan 465:470 arg1 attributes 489:498 Fc glycan critical quality attributes 462:498 Fc glycan critical quality attributes (CQAs) 462:505 Therefore, identification and detailed characterization of Fc glycan critical quality attributes (CQAs) provides important information for process design and control. 27160519 5 37 theme full-factorial 830:843 arg1 design 845:850 a full-factorial design 828:850 a full-factorial design of experiment (DOE) 828:870 Next, a full-factorial design of experiment (DOE) to characterize the possible interactions and relative effect of these three glycan species on ADCC, CDC, and FcγRIIIa binding was employed. 27160519 1 38 link N-linked 145:152 arg1 glycosylation 157:169 N-linked Fc glycosylation 145:169 N-linked Fc glycosylation of IgG1 monoclonal antibody therapeutics 145:210 N-linked Fc glycosylation of IgG1 monoclonal antibody therapeutics can directly influence their mechanism of action by impacting IgG effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). 27160519 6 39 theme given 1116:1120 arg1 configuration 1122:1134 a given configuration 1114:1134 a given configuration of the three glycan species 1114:1162 Additionally, the DOE data were used to develop models to predict ADCC, CDC, and FcγRIIIa binding of a given configuration of the three glycan species for this IgG1 molecule. 27160519 1 40 theme antibody 190:197 arg1 therapeutics 199:210 IgG1 monoclonal antibody therapeutics 174:210 IgG1 monoclonal antibody therapeutics 174:210 N-linked Fc glycosylation of IgG1 monoclonal antibody therapeutics can directly influence their mechanism of action by impacting IgG effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). 27160519 2 41 theme Fc 462:463 arg1 CQAs 501:504 CQAs 501:504 CQAs 501:504 Therefore, identification and detailed characterization of Fc glycan critical quality attributes (CQAs) provides important information for process design and control. 27160519 2 41 theme Fc 462:463 arg1 attributes 489:498 Fc glycan critical quality attributes 462:498 Fc glycan critical quality attributes (CQAs) 462:505 Therefore, identification and detailed characterization of Fc glycan critical quality attributes (CQAs) provides important information for process design and control. 27160519 2 42 dep process 542:548 arg1 design 550:555 design 550:555 design 550:555 Therefore, identification and detailed characterization of Fc glycan critical quality attributes (CQAs) provides important information for process design and control. 27160519 6 43 theme species 1156:1162 arg1 configuration 1122:1134 a given configuration 1114:1134 a given configuration of the three glycan species 1114:1162 Additionally, the DOE data were used to develop models to predict ADCC, CDC, and FcγRIIIa binding of a given configuration of the three glycan species for this IgG1 molecule. 27160519 1 44 theme therapeutics 199:210 arg1 glycosylation 157:169 N-linked Fc glycosylation 145:169 N-linked Fc glycosylation of IgG1 monoclonal antibody therapeutics 145:210 N-linked Fc glycosylation of IgG1 monoclonal antibody therapeutics can directly influence their mechanism of action by impacting IgG effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). 27160519 0 45 theme Fc 38:39 arg1 attributes 48:57 multiple Fc glycan attributes 29:57 multiple Fc glycan attributes 29:57 Characterizing the effect of multiple Fc glycan attributes on the effector functions and FcγRIIIa receptor binding activity of an IgG1 antibody. 27160519 0 46 theme IgG1 130:133 arg1 antibody 135:142 an IgG1 antibody 127:142 an IgG1 antibody 127:142 Characterizing the effect of multiple Fc glycan attributes on the effector functions and FcγRIIIa receptor binding activity of an IgG1 antibody. 27160519 3 47 theme effector 668:675 arg1 function 677:684 effector function 668:684 effector function 668:684 A two-step approach was used to identify and characterize the Fc glycan CQAs for an IgG1 Mab with effector function. 27160519 5 48 theme possible 892:899 arg1 interactions 901:912 the possible interactions 888:912 the possible interactions 888:912 Next, a full-factorial design of experiment (DOE) to characterize the possible interactions and relative effect of these three glycan species on ADCC, CDC, and FcγRIIIa binding was employed. 27160519 2 49 theme detailed 433:440 arg1 characterization 442:457 detailed characterization 433:457 detailed characterization 433:457 Therefore, identification and detailed characterization of Fc glycan critical quality attributes (CQAs) provides important information for process design and control. 27160519 0 50 theme multiple 29:36 arg1 attributes 48:57 multiple Fc glycan attributes 29:57 multiple Fc glycan attributes 29:57 Characterizing the effect of multiple Fc glycan attributes on the effector functions and FcγRIIIa receptor binding activity of an IgG1 antibody. 27160519 1 51 theme antibody-dependent 305:322 arg1 ADCC 352:355 ADCC 352:355 ADCC 352:355 N-linked Fc glycosylation of IgG1 monoclonal antibody therapeutics can directly influence their mechanism of action by impacting IgG effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). 27160519 1 51 theme antibody-dependent 305:322 arg1 cytotoxicity 338:349 antibody-dependent cell-mediated cytotoxicity 305:349 antibody-dependent cell-mediated cytotoxicity (ADCC) 305:356 N-linked Fc glycosylation of IgG1 monoclonal antibody therapeutics can directly influence their mechanism of action by impacting IgG effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). 27160519 3 52 theme IgG1 654:657 arg1 Mab 659:661 an IgG1 Mab 651:661 an IgG1 Mab 651:661 A two-step approach was used to identify and characterize the Fc glycan CQAs for an IgG1 Mab with effector function. 27160519 3 53 theme Fc 632:633 arg1 CQAs 642:645 the Fc glycan CQAs 628:645 the Fc glycan CQAs for an IgG1 Mab with effector function 628:684 A two-step approach was used to identify and characterize the Fc glycan CQAs for an IgG1 Mab with effector function. 27160519 0 54 theme attributes 48:57 arg1 effect 19:24 the effect 15:24 the effect of multiple Fc glycan attributes on the effector functions and FcγRIIIa receptor binding activity of an IgG1 antibody 15:142 Characterizing the effect of multiple Fc glycan attributes on the effector functions and FcγRIIIa receptor binding activity of an IgG1 antibody. 27160519 1 55 theme cell-mediated 324:336 arg1 ADCC 352:355 ADCC 352:355 ADCC 352:355 N-linked Fc glycosylation of IgG1 monoclonal antibody therapeutics can directly influence their mechanism of action by impacting IgG effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). 27160519 1 55 theme cell-mediated 324:336 arg1 cytotoxicity 338:349 antibody-dependent cell-mediated cytotoxicity 305:349 antibody-dependent cell-mediated cytotoxicity (ADCC) 305:356 N-linked Fc glycosylation of IgG1 monoclonal antibody therapeutics can directly influence their mechanism of action by impacting IgG effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). 27160519 9 56 theme modeling 1440:1447 arg1 type 1404:1407 This type 1399:1407 This type of glycan characterization and modeling 1399:1447 This type of glycan characterization and modeling can provide valuable information for development, manufacturing support and process improvements for IgG products that require effector function for efficacy. 27160519 0 57 theme glycan 41:46 arg1 attributes 48:57 multiple Fc glycan attributes 29:57 multiple Fc glycan attributes 29:57 Characterizing the effect of multiple Fc glycan attributes on the effector functions and FcγRIIIa receptor binding activity of an IgG1 antibody. 27160519 0 58 theme antibody 135:142 arg1 activity 115:122 FcγRIIIa receptor binding activity 89:122 FcγRIIIa receptor binding activity 89:122 Characterizing the effect of multiple Fc glycan attributes on the effector functions and FcγRIIIa receptor binding activity of an IgG1 antibody. 27160519 0 58 theme antibody 135:142 arg1 functions 75:83 effector functions 66:83 effector functions 66:83 Characterizing the effect of multiple Fc glycan attributes on the effector functions and FcγRIIIa receptor binding activity of an IgG1 antibody. 27160519 2 59 theme attributes 489:498 arg1 identification 414:427 identification 414:427 identification 414:427 Therefore, identification and detailed characterization of Fc glycan critical quality attributes (CQAs) provides important information for process design and control. 27160519 2 59 theme attributes 489:498 arg1 characterization 442:457 detailed characterization 433:457 detailed characterization 433:457 Therefore, identification and detailed characterization of Fc glycan critical quality attributes (CQAs) provides important information for process design and control. 27160519 9 60 theme IgG 1550:1552 arg1 products 1554:1561 IgG products 1550:1561 IgG products that require effector function for efficacy 1550:1605 This type of glycan characterization and modeling can provide valuable information for development, manufacturing support and process improvements for IgG products that require effector function for efficacy. 27160519 7 61 theme FcγRIIIa 1297:1304 arg1 binding 1306:1312 FcγRIIIa binding 1297:1312 FcγRIIIa binding 1297:1312 The results demonstrate that for ADCC, afuco mono/bi has the largest effect, followed by HM and β-gal, while FcγRIIIa binding is affected by afuco mono/bi and β-gal. 27160519 7 62 theme afuco 1329:1333 arg1 mono/bi 1335:1341 afuco mono/bi 1329:1341 afuco mono/bi 1329:1341 The results demonstrate that for ADCC, afuco mono/bi has the largest effect, followed by HM and β-gal, while FcγRIIIa binding is affected by afuco mono/bi and β-gal. 27160519 4 63 theme glycan 747:752 arg1 attributes 771:780 glycan critical quality attributes 747:780 glycan critical quality attributes that influence ADCC and CDC activities 747:819 First, single factor experiments were performed to identify glycan critical quality attributes that influence ADCC and CDC activities. 27160519 10 64 dep Biotechnol 1656:1665 arg1 Institute 1624:1632 Institute 1624:1632 Institute 1624:1632 © 2016 American Institute of Chemical Engineers Biotechnol. 27160519 6 65 theme DOE 1031:1033 arg1 data 1035:1038 the DOE data 1027:1038 the DOE data 1027:1038 Additionally, the DOE data were used to develop models to predict ADCC, CDC, and FcγRIIIa binding of a given configuration of the three glycan species for this IgG1 molecule. 27160519 9 66 theme valuable 1461:1468 arg1 information 1470:1480 valuable information 1461:1480 valuable information for development 1461:1496 This type of glycan characterization and modeling can provide valuable information for development, manufacturing support and process improvements for IgG products that require effector function for efficacy. 27160519 4 67 theme ADCC 797:800 arg1 activities 810:819 ADCC and CDC activities 797:819 ADCC and CDC activities 797:819 First, single factor experiments were performed to identify glycan critical quality attributes that influence ADCC and CDC activities. 27160519 5 68 theme glycan 949:954 arg1 species 956:962 these three glycan species 937:962 these three glycan species 937:962 Next, a full-factorial design of experiment (DOE) to characterize the possible interactions and relative effect of these three glycan species on ADCC, CDC, and FcγRIIIa binding was employed. 27160519 6 69 theme FcγRIIIa 1094:1101 arg1 binding 1103:1109 FcγRIIIa binding 1094:1109 FcγRIIIa binding 1094:1109 Additionally, the DOE data were used to develop models to predict ADCC, CDC, and FcγRIIIa binding of a given configuration of the three glycan species for this IgG1 molecule. 27160519 9 70 dep support 1513:1519 arg1 improvements 1533:1544 improvements 1533:1544 improvements 1533:1544 This type of glycan characterization and modeling can provide valuable information for development, manufacturing support and process improvements for IgG products that require effector function for efficacy. 27160519 3 71 theme glycan 635:640 arg1 CQAs 642:645 the Fc glycan CQAs 628:645 the Fc glycan CQAs for an IgG1 Mab with effector function 628:684 A two-step approach was used to identify and characterize the Fc glycan CQAs for an IgG1 Mab with effector function. 27160519 3 72 used used 594:597 arg2 approach 581:588 A two-step approach 570:588 A two-step approach 570:588 A two-step approach was used to identify and characterize the Fc glycan CQAs for an IgG1 Mab with effector function. 27160519 4 73 theme factor 701:706 arg1 experiments 708:718 single factor experiments 694:718 single factor experiments 694:718 First, single factor experiments were performed to identify glycan critical quality attributes that influence ADCC and CDC activities. 27160519 3 74 with CQAs 642:645 arg1 function 677:684 effector function 668:684 effector function 668:684 A two-step approach was used to identify and characterize the Fc glycan CQAs for an IgG1 Mab with effector function. 27160519 9 75 theme effector 1576:1583 arg1 function 1585:1592 effector function 1576:1592 effector function for efficacy 1576:1605 This type of glycan characterization and modeling can provide valuable information for development, manufacturing support and process improvements for IgG products that require effector function for efficacy. 27160519 7 76 theme afuco 1227:1231 arg1 mono/bi 1233:1239 afuco mono/bi 1227:1239 afuco mono/bi 1227:1239 The results demonstrate that for ADCC, afuco mono/bi has the largest effect, followed by HM and β-gal, while FcγRIIIa binding is affected by afuco mono/bi and β-gal. 27160519 4 77 theme single 694:699 arg1 experiments 708:718 single factor experiments 694:718 single factor experiments 694:718 First, single factor experiments were performed to identify glycan critical quality attributes that influence ADCC and CDC activities. 27685262 7 0 theme specific 1234:1241 arg1 chromatography 1158:1171 Affinity chromatography 1149:1171 Affinity chromatography 1149:1171 Affinity chromatography using both TL and Griffonia simplicifolia lectin II (GSLII), specific to non-reducing terminal residue of N-acetylglucosamine (GlcNAc), led to an enrichment of glycoproteins of the trypanosomal endocytic pathway. 27685262 6 1 theme endocytic 1047:1055 arg1 pathway 1057:1063 the endocytic pathway 1043:1063 the endocytic pathway 1043:1063 We show that in T. cruzi epimastigote forms also, glycoproteins of the endocytic pathway are characterized by the presence of N-linked glycans binding to both ricin and TL. 27685262 7 2 theme Affinity 1149:1156 arg1 chromatography 1158:1171 Affinity chromatography 1149:1171 Affinity chromatography 1149:1171 Affinity chromatography using both TL and Griffonia simplicifolia lectin II (GSLII), specific to non-reducing terminal residue of N-acetylglucosamine (GlcNAc), led to an enrichment of glycoproteins of the trypanosomal endocytic pathway. 27685262 2 3 theme dividing 393:400 arg1 forms 402:406 non-proliferative and dividing forms 371:406 non-proliferative and dividing forms 371:406 This parasite undergoes a complex life cycle alternating between non-proliferative and dividing forms. 27685262 1 4 theme Chagas 273:278 arg1 disease 280:286 causing human Chagas disease 259:286 causing human Chagas disease in South America 259:303 Trypanosoma cruzi is a protozoan parasite transmitted by a triatomine insect, and causing human Chagas disease in South America. 27685262 0 5 theme Binding 76:82 arg1 Lectin 84:89 a Poly-LAcNAc Binding Lectin 62:89 a Poly-LAcNAc Binding Lectin 62:89 Specific Endocytosis Blockade of Trypanosoma cruzi Exposed to a Poly-LAcNAc Binding Lectin Suggests that Lectin-Sugar Interactions Participate to Receptor-Mediated Endocytosis. 27685262 8 6 theme dextran 1541:1547 arg1 endocytosis 1501:1511 endocytosis 1501:1511 endocytosis of transferrin (Tf) but not dextran, a marker of fluid endocytosis 1501:1578 Incubation of live parasites with TL, which selectively bound to the cytostome/cytopharynx, specifically inhibited endocytosis of transferrin (Tf) but not dextran, a marker of fluid endocytosis. 27685262 9 7 theme crucial 1673:1679 arg1 role 1681:1684 a crucial role 1671:1684 a crucial role 1671:1684 Taken together, our data suggest that N-glycan modification of endocytic components plays a crucial role in receptor-mediated endocytosis of T. cruzi. 27685262 9 8 theme endocytic 1644:1652 arg1 components 1654:1663 endocytic components 1644:1663 endocytic components 1644:1663 Taken together, our data suggest that N-glycan modification of endocytic components plays a crucial role in receptor-mediated endocytosis of T. cruzi. 27685262 8 9 theme parasites 1405:1413 arg1 Incubation 1386:1395 Incubation 1386:1395 Incubation 1386:1395 Incubation of live parasites with TL, which selectively bound to the cytostome/cytopharynx, specifically inhibited endocytosis of transferrin (Tf) but not dextran, a marker of fluid endocytosis. 27685262 8 10 theme live 1400:1403 arg1 parasites 1405:1413 live parasites 1400:1413 live parasites 1400:1413 Incubation of live parasites with TL, which selectively bound to the cytostome/cytopharynx, specifically inhibited endocytosis of transferrin (Tf) but not dextran, a marker of fluid endocytosis. 27685262 7 11 theme N-acetylglucosamine 1279:1297 arg1 N-acetylglucosamine 1279:1297 N-acetylglucosamine 1279:1297 N-acetylglucosamine (GlcNAc) 1279:1306 Affinity chromatography using both TL and Griffonia simplicifolia lectin II (GSLII), specific to non-reducing terminal residue of N-acetylglucosamine (GlcNAc), led to an enrichment of glycoproteins of the trypanosomal endocytic pathway. 27685262 7 11 theme N-acetylglucosamine 1279:1297 arg1 residue 1268:1274 non-reducing terminal residue 1246:1274 non-reducing terminal residue of N-acetylglucosamine (GlcNAc) 1246:1306 Affinity chromatography using both TL and Griffonia simplicifolia lectin II (GSLII), specific to non-reducing terminal residue of N-acetylglucosamine (GlcNAc), led to an enrichment of glycoproteins of the trypanosomal endocytic pathway. 27685262 9 12 theme receptor-mediated 1689:1705 arg1 endocytosis 1707:1717 receptor-mediated endocytosis 1689:1717 receptor-mediated endocytosis of T. cruzi 1689:1729 Taken together, our data suggest that N-glycan modification of endocytic components plays a crucial role in receptor-mediated endocytosis of T. cruzi. 27685262 5 13 theme giant 903:907 arg1 chains 909:914 giant chains 903:914 giant chains of poly-LacNAc 903:929 In African trypanosomes tomato lectin (TL) and ricin, respectively specific to poly-N-acetyllactosamine (poly-LacNAc) and β-D-galactose, allowed the identification of giant chains of poly-LacNAc in N-glycoproteins of the endocytic pathway. 27685262 6 14 theme N-linked 1102:1109 arg1 glycans 1111:1117 N-linked glycans 1102:1117 N-linked glycans binding to both ricin and TL 1102:1146 We show that in T. cruzi epimastigote forms also, glycoproteins of the endocytic pathway are characterized by the presence of N-linked glycans binding to both ricin and TL. 27685262 0 15 theme Lectin-Sugar 105:116 arg1 Interactions 118:129 Lectin-Sugar Interactions 105:129 Lectin-Sugar Interactions 105:129 Specific Endocytosis Blockade of Trypanosoma cruzi Exposed to a Poly-LAcNAc Binding Lectin Suggests that Lectin-Sugar Interactions Participate to Receptor-Mediated Endocytosis. 27685262 5 16 theme specific 803:810 arg1 TL 775:776 TL 775:776 TL 775:776 In African trypanosomes tomato lectin (TL) and ricin, respectively specific to poly-N-acetyllactosamine (poly-LacNAc) and β-D-galactose, allowed the identification of giant chains of poly-LacNAc in N-glycoproteins of the endocytic pathway. 27685262 5 16 theme specific 803:810 arg1 lectin 767:772 tomato lectin 760:772 tomato lectin (TL) 760:777 In African trypanosomes tomato lectin (TL) and ricin, respectively specific to poly-N-acetyllactosamine (poly-LacNAc) and β-D-galactose, allowed the identification of giant chains of poly-LacNAc in N-glycoproteins of the endocytic pathway. 27685262 3 17 theme high 424:427 arg1 requirement 436:446 their high energy requirement 418:446 their high energy requirement 418:446 Owing to their high energy requirement, replicative epimastigotes of the insect midgut display high endocytic activity. 27685262 1 18 theme protozoan 200:208 arg1 parasite 210:217 a protozoan parasite 198:217 a protozoan parasite transmitted by a triatomine insect 198:252 Trypanosoma cruzi is a protozoan parasite transmitted by a triatomine insect, and causing human Chagas disease in South America. 27685262 1 18 theme protozoan 200:208 arg1 cruzi 189:193 Trypanosoma cruzi 177:193 Trypanosoma cruzi 177:193 Trypanosoma cruzi is a protozoan parasite transmitted by a triatomine insect, and causing human Chagas disease in South America. 27685262 0 19 theme Endocytosis 9:19 arg1 Blockade 21:28 Specific Endocytosis Blockade 0:28 Specific Endocytosis Blockade of Trypanosoma cruzi Exposed to a Poly-LAcNAc Binding Lectin 0:89 Specific Endocytosis Blockade of Trypanosoma cruzi Exposed to a Poly-LAcNAc Binding Lectin Suggests that Lectin-Sugar Interactions Participate to Receptor-Mediated Endocytosis. 27685262 7 20 theme non-reducing 1246:1257 arg1 N-acetylglucosamine 1279:1297 N-acetylglucosamine 1279:1297 N-acetylglucosamine (GlcNAc) 1279:1306 Affinity chromatography using both TL and Griffonia simplicifolia lectin II (GSLII), specific to non-reducing terminal residue of N-acetylglucosamine (GlcNAc), led to an enrichment of glycoproteins of the trypanosomal endocytic pathway. 27685262 7 20 theme non-reducing 1246:1257 arg1 residue 1268:1274 non-reducing terminal residue 1246:1274 non-reducing terminal residue of N-acetylglucosamine (GlcNAc) 1246:1306 Affinity chromatography using both TL and Griffonia simplicifolia lectin II (GSLII), specific to non-reducing terminal residue of N-acetylglucosamine (GlcNAc), led to an enrichment of glycoproteins of the trypanosomal endocytic pathway. 27685262 2 21 theme life 340:343 arg1 cycle 345:349 a complex life cycle 330:349 a complex life cycle alternating between non-proliferative and dividing forms 330:406 This parasite undergoes a complex life cycle alternating between non-proliferative and dividing forms. 27685262 5 22 theme chains 909:914 arg1 identification 885:898 the identification 881:898 the identification of giant chains of poly-LacNAc in N-glycoproteins of the endocytic pathway 881:973 In African trypanosomes tomato lectin (TL) and ricin, respectively specific to poly-N-acetyllactosamine (poly-LacNAc) and β-D-galactose, allowed the identification of giant chains of poly-LacNAc in N-glycoproteins of the endocytic pathway. 27685262 0 23 theme Specific 0:7 arg1 Blockade 21:28 Specific Endocytosis Blockade 0:28 Specific Endocytosis Blockade of Trypanosoma cruzi Exposed to a Poly-LAcNAc Binding Lectin 0:89 Specific Endocytosis Blockade of Trypanosoma cruzi Exposed to a Poly-LAcNAc Binding Lectin Suggests that Lectin-Sugar Interactions Participate to Receptor-Mediated Endocytosis. 27685262 8 24 theme endocytosis 1568:1578 arg1 dextran 1541:1547 dextran 1541:1547 dextran 1541:1547 Incubation of live parasites with TL, which selectively bound to the cytostome/cytopharynx, specifically inhibited endocytosis of transferrin (Tf) but not dextran, a marker of fluid endocytosis. 27685262 8 24 theme endocytosis 1568:1578 arg1 marker 1552:1557 a marker 1550:1557 a marker of fluid endocytosis 1550:1578 Incubation of live parasites with TL, which selectively bound to the cytostome/cytopharynx, specifically inhibited endocytosis of transferrin (Tf) but not dextran, a marker of fluid endocytosis. 27685262 7 25 gly glycoproteins 1333:1345 arg1 glycoproteins 1333:1345 glycoproteins 1333:1345 glycoproteins of the trypanosomal endocytic pathway 1333:1383 Affinity chromatography using both TL and Griffonia simplicifolia lectin II (GSLII), specific to non-reducing terminal residue of N-acetylglucosamine (GlcNAc), led to an enrichment of glycoproteins of the trypanosomal endocytic pathway. 27685262 2 26 theme complex 332:338 arg1 cycle 345:349 a complex life cycle 330:349 a complex life cycle alternating between non-proliferative and dividing forms 330:406 This parasite undergoes a complex life cycle alternating between non-proliferative and dividing forms. 27685262 7 27 theme Griffonia 1191:1199 arg1 lectin 1215:1220 Griffonia simplicifolia lectin II 1191:1223 Griffonia simplicifolia lectin II (GSLII) 1191:1231 Affinity chromatography using both TL and Griffonia simplicifolia lectin II (GSLII), specific to non-reducing terminal residue of N-acetylglucosamine (GlcNAc), led to an enrichment of glycoproteins of the trypanosomal endocytic pathway. 27685262 7 27 theme Griffonia 1191:1199 arg1 GSLII 1226:1230 GSLII 1226:1230 GSLII 1226:1230 Affinity chromatography using both TL and Griffonia simplicifolia lectin II (GSLII), specific to non-reducing terminal residue of N-acetylglucosamine (GlcNAc), led to an enrichment of glycoproteins of the trypanosomal endocytic pathway. 27685262 6 28 theme glycans 1111:1117 arg1 presence 1090:1097 the presence 1086:1097 the presence of N-linked glycans binding to both ricin and TL 1086:1146 We show that in T. cruzi epimastigote forms also, glycoproteins of the endocytic pathway are characterized by the presence of N-linked glycans binding to both ricin and TL. 27685262 3 29 theme high 504:507 arg1 activity 519:526 high endocytic activity 504:526 high endocytic activity 504:526 Owing to their high energy requirement, replicative epimastigotes of the insect midgut display high endocytic activity. 27685262 7 30 theme simplicifolia 1201:1213 arg1 lectin 1215:1220 Griffonia simplicifolia lectin II 1191:1223 Griffonia simplicifolia lectin II (GSLII) 1191:1231 Affinity chromatography using both TL and Griffonia simplicifolia lectin II (GSLII), specific to non-reducing terminal residue of N-acetylglucosamine (GlcNAc), led to an enrichment of glycoproteins of the trypanosomal endocytic pathway. 27685262 7 30 theme simplicifolia 1201:1213 arg1 GSLII 1226:1230 GSLII 1226:1230 GSLII 1226:1230 Affinity chromatography using both TL and Griffonia simplicifolia lectin II (GSLII), specific to non-reducing terminal residue of N-acetylglucosamine (GlcNAc), led to an enrichment of glycoproteins of the trypanosomal endocytic pathway. 27685262 5 31 theme African 739:745 arg1 trypanosomes 747:758 African trypanosomes 739:758 African trypanosomes 739:758 In African trypanosomes tomato lectin (TL) and ricin, respectively specific to poly-N-acetyllactosamine (poly-LacNAc) and β-D-galactose, allowed the identification of giant chains of poly-LacNAc in N-glycoproteins of the endocytic pathway. 27685262 7 32 theme glycoproteins 1333:1345 arg1 enrichment 1319:1328 an enrichment 1316:1328 an enrichment of glycoproteins of the trypanosomal endocytic pathway 1316:1383 Affinity chromatography using both TL and Griffonia simplicifolia lectin II (GSLII), specific to non-reducing terminal residue of N-acetylglucosamine (GlcNAc), led to an enrichment of glycoproteins of the trypanosomal endocytic pathway. 27685262 3 33 theme endocytic 509:517 arg1 activity 519:526 high endocytic activity 504:526 high endocytic activity 504:526 Owing to their high energy requirement, replicative epimastigotes of the insect midgut display high endocytic activity. 27685262 0 34 theme cruzi 45:49 arg1 Blockade 21:28 Specific Endocytosis Blockade 0:28 Specific Endocytosis Blockade of Trypanosoma cruzi Exposed to a Poly-LAcNAc Binding Lectin 0:89 Specific Endocytosis Blockade of Trypanosoma cruzi Exposed to a Poly-LAcNAc Binding Lectin Suggests that Lectin-Sugar Interactions Participate to Receptor-Mediated Endocytosis. 27685262 6 35 theme T. 992:993 arg1 forms 1014:1018 T. cruzi epimastigote forms 992:1018 T. cruzi epimastigote forms also 992:1023 We show that in T. cruzi epimastigote forms also, glycoproteins of the endocytic pathway are characterized by the presence of N-linked glycans binding to both ricin and TL. 27685262 9 36 theme T. 1722:1723 arg1 endocytosis 1707:1717 receptor-mediated endocytosis 1689:1717 receptor-mediated endocytosis of T. cruzi 1689:1729 Taken together, our data suggest that N-glycan modification of endocytic components plays a crucial role in receptor-mediated endocytosis of T. cruzi. 27685262 3 37 theme midgut 489:494 arg1 epimastigotes 461:473 replicative epimastigotes 449:473 replicative epimastigotes of the insect midgut 449:494 Owing to their high energy requirement, replicative epimastigotes of the insect midgut display high endocytic activity. 27685262 5 38 theme tomato 760:765 arg1 TL 775:776 TL 775:776 TL 775:776 In African trypanosomes tomato lectin (TL) and ricin, respectively specific to poly-N-acetyllactosamine (poly-LacNAc) and β-D-galactose, allowed the identification of giant chains of poly-LacNAc in N-glycoproteins of the endocytic pathway. 27685262 5 38 theme tomato 760:765 arg1 lectin 767:772 tomato lectin 760:772 tomato lectin (TL) 760:777 In African trypanosomes tomato lectin (TL) and ricin, respectively specific to poly-N-acetyllactosamine (poly-LacNAc) and β-D-galactose, allowed the identification of giant chains of poly-LacNAc in N-glycoproteins of the endocytic pathway. 27685262 1 39 theme triatomine 236:245 arg1 insect 247:252 a triatomine insect 234:252 a triatomine insect 234:252 Trypanosoma cruzi is a protozoan parasite transmitted by a triatomine insect, and causing human Chagas disease in South America. 27685262 0 40 theme Trypanosoma 33:43 arg1 cruzi 45:49 Trypanosoma cruzi 33:49 Trypanosoma cruzi Exposed to a Poly-LAcNAc Binding Lectin 33:89 Specific Endocytosis Blockade of Trypanosoma cruzi Exposed to a Poly-LAcNAc Binding Lectin Suggests that Lectin-Sugar Interactions Participate to Receptor-Mediated Endocytosis. 27685262 0 41 theme Receptor-Mediated 146:162 arg1 Endocytosis 164:174 Receptor-Mediated Endocytosis 146:174 Receptor-Mediated Endocytosis 146:174 Specific Endocytosis Blockade of Trypanosoma cruzi Exposed to a Poly-LAcNAc Binding Lectin Suggests that Lectin-Sugar Interactions Participate to Receptor-Mediated Endocytosis. 27685262 4 42 theme vesicular 646:654 arg1 network 656:662 the endosomal vesicular network 632:662 the endosomal vesicular network to be delivered to reservosomes, the final lysosomal-like compartments 632:733 This activity is mainly restricted to the cytostome, by which the cargo is taken up and sorted through the endosomal vesicular network to be delivered to reservosomes, the final lysosomal-like compartments. 27685262 6 43 gly glycoproteins 1026:1038 arg1 glycoproteins 1026:1038 glycoproteins 1026:1038 glycoproteins of the endocytic pathway 1026:1063 We show that in T. cruzi epimastigote forms also, glycoproteins of the endocytic pathway are characterized by the presence of N-linked glycans binding to both ricin and TL. 27685262 3 44 theme energy 429:434 arg1 requirement 436:446 their high energy requirement 418:446 their high energy requirement 418:446 Owing to their high energy requirement, replicative epimastigotes of the insect midgut display high endocytic activity. 27685262 5 45 theme poly-LacNAc 919:929 arg1 chains 909:914 giant chains 903:914 giant chains of poly-LacNAc 903:929 In African trypanosomes tomato lectin (TL) and ricin, respectively specific to poly-N-acetyllactosamine (poly-LacNAc) and β-D-galactose, allowed the identification of giant chains of poly-LacNAc in N-glycoproteins of the endocytic pathway. 27685262 6 46 theme epimastigote 1001:1012 arg1 forms 1014:1018 T. cruzi epimastigote forms 992:1018 T. cruzi epimastigote forms also 992:1023 We show that in T. cruzi epimastigote forms also, glycoproteins of the endocytic pathway are characterized by the presence of N-linked glycans binding to both ricin and TL. 27685262 9 47 theme N-glycan 1619:1626 arg1 modification 1628:1639 N-glycan modification 1619:1639 N-glycan modification of endocytic components 1619:1663 Taken together, our data suggest that N-glycan modification of endocytic components plays a crucial role in receptor-mediated endocytosis of T. cruzi. 27685262 5 48 from identification 885:898 arg1 N-glycoproteins 934:948 N-glycoproteins 934:948 N-glycoproteins of the endocytic pathway 934:973 In African trypanosomes tomato lectin (TL) and ricin, respectively specific to poly-N-acetyllactosamine (poly-LacNAc) and β-D-galactose, allowed the identification of giant chains of poly-LacNAc in N-glycoproteins of the endocytic pathway. 27685262 2 49 theme non-proliferative 371:387 arg1 forms 402:406 non-proliferative and dividing forms 371:406 non-proliferative and dividing forms 371:406 This parasite undergoes a complex life cycle alternating between non-proliferative and dividing forms. 27685262 1 50 from disease 280:286 arg1 America 297:303 America 297:303 America 297:303 Trypanosoma cruzi is a protozoan parasite transmitted by a triatomine insect, and causing human Chagas disease in South America. 27685262 6 51 link N-linked 1102:1109 arg1 glycans 1111:1117 N-linked glycans 1102:1117 N-linked glycans binding to both ricin and TL 1102:1146 We show that in T. cruzi epimastigote forms also, glycoproteins of the endocytic pathway are characterized by the presence of N-linked glycans binding to both ricin and TL. 27685262 8 52 theme transferrin 1516:1526 arg1 endocytosis 1501:1511 endocytosis 1501:1511 endocytosis of transferrin (Tf) but not dextran, a marker of fluid endocytosis 1501:1578 Incubation of live parasites with TL, which selectively bound to the cytostome/cytopharynx, specifically inhibited endocytosis of transferrin (Tf) but not dextran, a marker of fluid endocytosis. 27685262 9 53 theme components 1654:1663 arg1 modification 1628:1639 N-glycan modification 1619:1639 N-glycan modification of endocytic components 1619:1663 Taken together, our data suggest that N-glycan modification of endocytic components plays a crucial role in receptor-mediated endocytosis of T. cruzi. 27685262 7 54 theme trypanosomal 1354:1365 arg1 pathway 1377:1383 the trypanosomal endocytic pathway 1350:1383 the trypanosomal endocytic pathway 1350:1383 Affinity chromatography using both TL and Griffonia simplicifolia lectin II (GSLII), specific to non-reducing terminal residue of N-acetylglucosamine (GlcNAc), led to an enrichment of glycoproteins of the trypanosomal endocytic pathway. 27685262 5 55 theme endocytic 957:965 arg1 pathway 967:973 the endocytic pathway 953:973 the endocytic pathway 953:973 In African trypanosomes tomato lectin (TL) and ricin, respectively specific to poly-N-acetyllactosamine (poly-LacNAc) and β-D-galactose, allowed the identification of giant chains of poly-LacNAc in N-glycoproteins of the endocytic pathway. 27685262 7 56 theme pathway 1377:1383 arg1 glycoproteins 1333:1345 glycoproteins 1333:1345 glycoproteins of the trypanosomal endocytic pathway 1333:1383 Affinity chromatography using both TL and Griffonia simplicifolia lectin II (GSLII), specific to non-reducing terminal residue of N-acetylglucosamine (GlcNAc), led to an enrichment of glycoproteins of the trypanosomal endocytic pathway. 27685262 6 57 dep T. 992:993 arg1 cruzi 995:999 cruzi 995:999 cruzi 995:999 We show that in T. cruzi epimastigote forms also, glycoproteins of the endocytic pathway are characterized by the presence of N-linked glycans binding to both ricin and TL. 27685262 5 58 theme pathway 967:973 arg1 N-glycoproteins 934:948 N-glycoproteins 934:948 N-glycoproteins of the endocytic pathway 934:973 In African trypanosomes tomato lectin (TL) and ricin, respectively specific to poly-N-acetyllactosamine (poly-LacNAc) and β-D-galactose, allowed the identification of giant chains of poly-LacNAc in N-glycoproteins of the endocytic pathway. 27685262 8 59 with Incubation 1386:1395 arg1 TL 1420:1421 TL 1420:1421 TL 1420:1421 Incubation of live parasites with TL, which selectively bound to the cytostome/cytopharynx, specifically inhibited endocytosis of transferrin (Tf) but not dextran, a marker of fluid endocytosis. 27685262 5 60 gly N-glycoproteins 934:948 arg1 N-glycoproteins 934:948 N-glycoproteins 934:948 N-glycoproteins of the endocytic pathway 934:973 In African trypanosomes tomato lectin (TL) and ricin, respectively specific to poly-N-acetyllactosamine (poly-LacNAc) and β-D-galactose, allowed the identification of giant chains of poly-LacNAc in N-glycoproteins of the endocytic pathway. 27685262 9 61 mod modification 1628:1639 arg3 N-glycan 1619:1626 N-glycan modification 1619:1639 N-glycan modification of endocytic components 1619:1663 Taken together, our data suggest that N-glycan modification of endocytic components plays a crucial role in receptor-mediated endocytosis of T. cruzi. 27685262 9 61 mod modification 1628:1639 arg1 components 1654:1663 endocytic components 1644:1663 endocytic components 1644:1663 Taken together, our data suggest that N-glycan modification of endocytic components plays a crucial role in receptor-mediated endocytosis of T. cruzi. 27685262 1 62 from parasite 210:217 arg1 America 297:303 America 297:303 America 297:303 Trypanosoma cruzi is a protozoan parasite transmitted by a triatomine insect, and causing human Chagas disease in South America. 27685262 4 63 theme final 701:705 arg1 compartments 722:733 the final lysosomal-like compartments 697:733 the final lysosomal-like compartments 697:733 This activity is mainly restricted to the cytostome, by which the cargo is taken up and sorted through the endosomal vesicular network to be delivered to reservosomes, the final lysosomal-like compartments. 27685262 4 63 theme final 701:705 arg1 reservosomes 683:694 reservosomes 683:694 reservosomes 683:694 This activity is mainly restricted to the cytostome, by which the cargo is taken up and sorted through the endosomal vesicular network to be delivered to reservosomes, the final lysosomal-like compartments. 27685262 6 64 theme pathway 1057:1063 arg1 glycoproteins 1026:1038 glycoproteins 1026:1038 glycoproteins of the endocytic pathway 1026:1063 We show that in T. cruzi epimastigote forms also, glycoproteins of the endocytic pathway are characterized by the presence of N-linked glycans binding to both ricin and TL. 27685262 0 65 theme Poly-LAcNAc 64:74 arg1 Lectin 84:89 a Poly-LAcNAc Binding Lectin 62:89 a Poly-LAcNAc Binding Lectin 62:89 Specific Endocytosis Blockade of Trypanosoma cruzi Exposed to a Poly-LAcNAc Binding Lectin Suggests that Lectin-Sugar Interactions Participate to Receptor-Mediated Endocytosis. 27685262 7 66 theme endocytic 1367:1375 arg1 pathway 1377:1383 the trypanosomal endocytic pathway 1350:1383 the trypanosomal endocytic pathway 1350:1383 Affinity chromatography using both TL and Griffonia simplicifolia lectin II (GSLII), specific to non-reducing terminal residue of N-acetylglucosamine (GlcNAc), led to an enrichment of glycoproteins of the trypanosomal endocytic pathway. 27685262 8 67 theme fluid 1562:1566 arg1 endocytosis 1568:1578 fluid endocytosis 1562:1578 fluid endocytosis 1562:1578 Incubation of live parasites with TL, which selectively bound to the cytostome/cytopharynx, specifically inhibited endocytosis of transferrin (Tf) but not dextran, a marker of fluid endocytosis. 27685262 4 68 theme lysosomal-like 707:720 arg1 compartments 722:733 the final lysosomal-like compartments 697:733 the final lysosomal-like compartments 697:733 This activity is mainly restricted to the cytostome, by which the cargo is taken up and sorted through the endosomal vesicular network to be delivered to reservosomes, the final lysosomal-like compartments. 27685262 4 68 theme lysosomal-like 707:720 arg1 reservosomes 683:694 reservosomes 683:694 reservosomes 683:694 This activity is mainly restricted to the cytostome, by which the cargo is taken up and sorted through the endosomal vesicular network to be delivered to reservosomes, the final lysosomal-like compartments. 27685262 3 69 theme insect 482:487 arg1 midgut 489:494 the insect midgut 478:494 the insect midgut 478:494 Owing to their high energy requirement, replicative epimastigotes of the insect midgut display high endocytic activity. 27685262 1 70 theme causing 259:265 arg1 disease 280:286 causing human Chagas disease 259:286 causing human Chagas disease in South America 259:303 Trypanosoma cruzi is a protozoan parasite transmitted by a triatomine insect, and causing human Chagas disease in South America. 27685262 7 71 theme terminal 1259:1266 arg1 N-acetylglucosamine 1279:1297 N-acetylglucosamine 1279:1297 N-acetylglucosamine (GlcNAc) 1279:1306 Affinity chromatography using both TL and Griffonia simplicifolia lectin II (GSLII), specific to non-reducing terminal residue of N-acetylglucosamine (GlcNAc), led to an enrichment of glycoproteins of the trypanosomal endocytic pathway. 27685262 7 71 theme terminal 1259:1266 arg1 residue 1268:1274 non-reducing terminal residue 1246:1274 non-reducing terminal residue of N-acetylglucosamine (GlcNAc) 1246:1306 Affinity chromatography using both TL and Griffonia simplicifolia lectin II (GSLII), specific to non-reducing terminal residue of N-acetylglucosamine (GlcNAc), led to an enrichment of glycoproteins of the trypanosomal endocytic pathway. 27685262 3 72 theme replicative 449:459 arg1 epimastigotes 461:473 replicative epimastigotes 449:473 replicative epimastigotes of the insect midgut 449:494 Owing to their high energy requirement, replicative epimastigotes of the insect midgut display high endocytic activity. 27685262 4 73 theme endosomal 636:644 arg1 network 656:662 the endosomal vesicular network 632:662 the endosomal vesicular network to be delivered to reservosomes, the final lysosomal-like compartments 632:733 This activity is mainly restricted to the cytostome, by which the cargo is taken up and sorted through the endosomal vesicular network to be delivered to reservosomes, the final lysosomal-like compartments. 27685262 1 74 theme Trypanosoma 177:187 arg1 parasite 210:217 a protozoan parasite 198:217 a protozoan parasite transmitted by a triatomine insect 198:252 Trypanosoma cruzi is a protozoan parasite transmitted by a triatomine insect, and causing human Chagas disease in South America. 27685262 1 74 theme Trypanosoma 177:187 arg1 cruzi 189:193 Trypanosoma cruzi 177:193 Trypanosoma cruzi 177:193 Trypanosoma cruzi is a protozoan parasite transmitted by a triatomine insect, and causing human Chagas disease in South America. 27685262 1 75 theme human 267:271 arg1 disease 280:286 causing human Chagas disease 259:286 causing human Chagas disease in South America 259:303 Trypanosoma cruzi is a protozoan parasite transmitted by a triatomine insect, and causing human Chagas disease in South America. 27573187 4 0 theme apparent 852:859 arg1 AQY 876:878 AQY 876:878 AQY 876:878 The apparent quantum yield (AQY) reaches (9.9±0.8) % at 420 nm. 27573187 4 0 theme apparent 852:859 arg1 yield 869:873 The apparent quantum yield 848:873 The apparent quantum yield (AQY) 848:879 The apparent quantum yield (AQY) reaches (9.9±0.8) % at 420 nm. 27573187 1 1 theme hydrogen-evolving 141:157 arg1 catalyst 168:175 a hydrogen-evolving molecule catalyst 139:175 a hydrogen-evolving molecule catalyst 139:175 The development of an artificial heterogeneous dyad by covalently anchoring a hydrogen-evolving molecule catalyst to a semiconductor photosensitizer through a bridging ligand is highly challenging. 27573187 1 2 theme molecule 159:166 arg1 catalyst 168:175 a hydrogen-evolving molecule catalyst 139:175 a hydrogen-evolving molecule catalyst 139:175 The development of an artificial heterogeneous dyad by covalently anchoring a hydrogen-evolving molecule catalyst to a semiconductor photosensitizer through a bridging ligand is highly challenging. 27573187 6 3 theme III 1303:1305 arg1 system 1280:1285 the mixed system 1270:1285 the mixed system of CdS-DETA and III 1270:1305 Furthermore, its TON value based on Ni species is also higher than that of the mixed system of CdS-DETA and III. 27573187 3 4 theme 0.47 s-1 787:794 arg1 TON 689:691 TON 689:691 TON 689:691 The [CdS-N=CH-Ni] enables a turnover number (TON) of about 43 815 versus Ni catalysts and an initial turnover frequency (TOF) of approximately 0.47 s-1 in 26 h under visible-light irradiation (λ>420 nm). 27573187 3 4 theme 0.47 s-1 787:794 arg1 number 681:686 a turnover number 670:686 a turnover number (TON) of about 43 815 versus Ni catalysts 670:728 The [CdS-N=CH-Ni] enables a turnover number (TON) of about 43 815 versus Ni catalysts and an initial turnover frequency (TOF) of approximately 0.47 s-1 in 26 h under visible-light irradiation (λ>420 nm). 27573187 3 4 theme 0.47 s-1 787:794 arg1 frequency 754:762 an initial turnover frequency 734:762 an initial turnover frequency (TOF) of approximately 0.47 s-1 in 26 h 734:802 The [CdS-N=CH-Ni] enables a turnover number (TON) of about 43 815 versus Ni catalysts and an initial turnover frequency (TOF) of approximately 0.47 s-1 in 26 h under visible-light irradiation (λ>420 nm). 27573187 3 4 theme 0.47 s-1 787:794 arg1 TOF 765:767 TOF 765:767 TOF 765:767 The [CdS-N=CH-Ni] enables a turnover number (TON) of about 43 815 versus Ni catalysts and an initial turnover frequency (TOF) of approximately 0.47 s-1 in 26 h under visible-light irradiation (λ>420 nm). 27573187 6 5 theme Ni 1231:1232 arg1 species 1234:1240 Ni species 1231:1240 Ni species 1231:1240 Furthermore, its TON value based on Ni species is also higher than that of the mixed system of CdS-DETA and III. 27573187 2 6 theme initial 365:371 arg1 matrix 373:378 initial matrix 365:378 initial matrix 365:378 Herein, we adopt the inorganic-organic hybrid CdS-DETA NSs (DETA=diethylenetriamine, NSs=nanosheets) as initial matrix to successfully construct an imine bond (-CH=N-) linked heterogeneous dyad [CdS-N=CH-Ni] through the condensation reaction between the amino groups of CdS-DETA and the aldehyde group of the water reduction molecular catalyst, [(tpy-CHO)2 Ni]Cl2 (tpy=terpyridine). 27573187 2 7 theme hybrid 300:305 arg1 NSs 316:318 the inorganic-organic hybrid CdS-DETA NSs 278:318 the inorganic-organic hybrid CdS-DETA NSs (DETA=diethylenetriamine, NSs=nanosheets) as initial matrix to successfully construct an imine bond (-CH=N-) linked heterogeneous dyad [CdS-N=CH-Ni] through the condensation reaction between the amino groups of CdS-DETA and the aldehyde group of the water reduction molecular catalyst, [(tpy-CHO)2 Ni]Cl2 (tpy=terpyridine) 278:641 Herein, we adopt the inorganic-organic hybrid CdS-DETA NSs (DETA=diethylenetriamine, NSs=nanosheets) as initial matrix to successfully construct an imine bond (-CH=N-) linked heterogeneous dyad [CdS-N=CH-Ni] through the condensation reaction between the amino groups of CdS-DETA and the aldehyde group of the water reduction molecular catalyst, [(tpy-CHO)2 Ni]Cl2 (tpy=terpyridine). 27573187 1 8 theme artificial 85:94 arg1 dyad 110:113 an artificial heterogeneous dyad 82:113 an artificial heterogeneous dyad 82:113 The development of an artificial heterogeneous dyad by covalently anchoring a hydrogen-evolving molecule catalyst to a semiconductor photosensitizer through a bridging ligand is highly challenging. 27573187 5 9 theme NSs 1122:1124 arg1 system 1103:1108 the mechanically mixed system 1080:1108 the mechanically mixed system of CdS-DETA NSs and [(tpy-CH=NR)2 Ni]Cl2 (III) 1080:1155 Under optical conditions, the [CdS-N=CH-Ni] can achieve a considerable amount of hydrogen production, 507.1±27 μmol H2 for 6 h, which is 1.27 times that generated from the mechanically mixed system of CdS-DETA NSs and [(tpy-CH=NR)2 Ni]Cl2 (III) under otherwise identical conditions. 27573187 2 10 theme inorganic-organic 282:298 arg1 NSs 316:318 the inorganic-organic hybrid CdS-DETA NSs 278:318 the inorganic-organic hybrid CdS-DETA NSs (DETA=diethylenetriamine, NSs=nanosheets) as initial matrix to successfully construct an imine bond (-CH=N-) linked heterogeneous dyad [CdS-N=CH-Ni] through the condensation reaction between the amino groups of CdS-DETA and the aldehyde group of the water reduction molecular catalyst, [(tpy-CHO)2 Ni]Cl2 (tpy=terpyridine) 278:641 Herein, we adopt the inorganic-organic hybrid CdS-DETA NSs (DETA=diethylenetriamine, NSs=nanosheets) as initial matrix to successfully construct an imine bond (-CH=N-) linked heterogeneous dyad [CdS-N=CH-Ni] through the condensation reaction between the amino groups of CdS-DETA and the aldehyde group of the water reduction molecular catalyst, [(tpy-CHO)2 Ni]Cl2 (tpy=terpyridine). 27573187 2 11 theme CdS-DETA 531:538 arg1 CdS-DETA 531:538 CdS-DETA 531:538 CdS-DETA 531:538 Herein, we adopt the inorganic-organic hybrid CdS-DETA NSs (DETA=diethylenetriamine, NSs=nanosheets) as initial matrix to successfully construct an imine bond (-CH=N-) linked heterogeneous dyad [CdS-N=CH-Ni] through the condensation reaction between the amino groups of CdS-DETA and the aldehyde group of the water reduction molecular catalyst, [(tpy-CHO)2 Ni]Cl2 (tpy=terpyridine). 27573187 2 11 theme CdS-DETA 531:538 arg1 Cl2 621:623 [(tpy-CHO)2 Ni]Cl2 606:623 [(tpy-CHO)2 Ni]Cl2 (tpy=terpyridine) 606:641 Herein, we adopt the inorganic-organic hybrid CdS-DETA NSs (DETA=diethylenetriamine, NSs=nanosheets) as initial matrix to successfully construct an imine bond (-CH=N-) linked heterogeneous dyad [CdS-N=CH-Ni] through the condensation reaction between the amino groups of CdS-DETA and the aldehyde group of the water reduction molecular catalyst, [(tpy-CHO)2 Ni]Cl2 (tpy=terpyridine). 27573187 2 11 theme CdS-DETA 531:538 arg1 groups 521:526 the amino groups 511:526 the amino groups of CdS-DETA 511:538 Herein, we adopt the inorganic-organic hybrid CdS-DETA NSs (DETA=diethylenetriamine, NSs=nanosheets) as initial matrix to successfully construct an imine bond (-CH=N-) linked heterogeneous dyad [CdS-N=CH-Ni] through the condensation reaction between the amino groups of CdS-DETA and the aldehyde group of the water reduction molecular catalyst, [(tpy-CHO)2 Ni]Cl2 (tpy=terpyridine). 27573187 2 11 theme CdS-DETA 531:538 arg1 group 557:561 the aldehyde group 544:561 the aldehyde group of the water reduction molecular catalyst, [(tpy-CHO)2 Ni]Cl2 (tpy=terpyridine) 544:641 Herein, we adopt the inorganic-organic hybrid CdS-DETA NSs (DETA=diethylenetriamine, NSs=nanosheets) as initial matrix to successfully construct an imine bond (-CH=N-) linked heterogeneous dyad [CdS-N=CH-Ni] through the condensation reaction between the amino groups of CdS-DETA and the aldehyde group of the water reduction molecular catalyst, [(tpy-CHO)2 Ni]Cl2 (tpy=terpyridine). 27573187 2 11 theme CdS-DETA 531:538 arg1 catalyst 596:603 the water reduction molecular catalyst 566:603 the water reduction molecular catalyst 566:603 Herein, we adopt the inorganic-organic hybrid CdS-DETA NSs (DETA=diethylenetriamine, NSs=nanosheets) as initial matrix to successfully construct an imine bond (-CH=N-) linked heterogeneous dyad [CdS-N=CH-Ni] through the condensation reaction between the amino groups of CdS-DETA and the aldehyde group of the water reduction molecular catalyst, [(tpy-CHO)2 Ni]Cl2 (tpy=terpyridine). 27573187 2 12 dep NSs 316:318 arg1 NSs=nanosheets 346:359 NSs=nanosheets 346:359 NSs=nanosheets 346:359 Herein, we adopt the inorganic-organic hybrid CdS-DETA NSs (DETA=diethylenetriamine, NSs=nanosheets) as initial matrix to successfully construct an imine bond (-CH=N-) linked heterogeneous dyad [CdS-N=CH-Ni] through the condensation reaction between the amino groups of CdS-DETA and the aldehyde group of the water reduction molecular catalyst, [(tpy-CHO)2 Ni]Cl2 (tpy=terpyridine). 27573187 2 12 dep NSs 316:318 arg1 DETA=diethylenetriamine 321:343 DETA=diethylenetriamine 321:343 DETA=diethylenetriamine 321:343 Herein, we adopt the inorganic-organic hybrid CdS-DETA NSs (DETA=diethylenetriamine, NSs=nanosheets) as initial matrix to successfully construct an imine bond (-CH=N-) linked heterogeneous dyad [CdS-N=CH-Ni] through the condensation reaction between the amino groups of CdS-DETA and the aldehyde group of the water reduction molecular catalyst, [(tpy-CHO)2 Ni]Cl2 (tpy=terpyridine). 27573187 5 13 theme production 1002:1011 arg1 H2 1028:1029 507.1±27 μmol H2 1014:1029 507.1±27 μmol H2 for 6 h 1014:1037 Under optical conditions, the [CdS-N=CH-Ni] can achieve a considerable amount of hydrogen production, 507.1±27 μmol H2 for 6 h, which is 1.27 times that generated from the mechanically mixed system of CdS-DETA NSs and [(tpy-CH=NR)2 Ni]Cl2 (III) under otherwise identical conditions. 27573187 5 13 theme production 1002:1011 arg1 amount 983:988 a considerable amount 968:988 a considerable amount of hydrogen production, 507.1±27 μmol H2 for 6 h, which is 1.27 times that generated from the mechanically mixed system of CdS-DETA NSs and [(tpy-CH=NR)2 Ni]Cl2 (III) under otherwise identical conditions 968:1192 Under optical conditions, the [CdS-N=CH-Ni] can achieve a considerable amount of hydrogen production, 507.1±27 μmol H2 for 6 h, which is 1.27 times that generated from the mechanically mixed system of CdS-DETA NSs and [(tpy-CH=NR)2 Ni]Cl2 (III) under otherwise identical conditions. 27573187 5 13 theme production 1002:1011 arg1 production 1002:1011 hydrogen production 993:1011 hydrogen production 993:1011 Under optical conditions, the [CdS-N=CH-Ni] can achieve a considerable amount of hydrogen production, 507.1±27 μmol H2 for 6 h, which is 1.27 times that generated from the mechanically mixed system of CdS-DETA NSs and [(tpy-CH=NR)2 Ni]Cl2 (III) under otherwise identical conditions. 27573187 5 14 theme 507.1±27 μmol 1014:1026 arg1 H2 1028:1029 507.1±27 μmol H2 1014:1029 507.1±27 μmol H2 for 6 h 1014:1037 Under optical conditions, the [CdS-N=CH-Ni] can achieve a considerable amount of hydrogen production, 507.1±27 μmol H2 for 6 h, which is 1.27 times that generated from the mechanically mixed system of CdS-DETA NSs and [(tpy-CH=NR)2 Ni]Cl2 (III) under otherwise identical conditions. 27573187 5 14 theme 507.1±27 μmol 1014:1026 arg1 production 1002:1011 hydrogen production 993:1011 hydrogen production 993:1011 Under optical conditions, the [CdS-N=CH-Ni] can achieve a considerable amount of hydrogen production, 507.1±27 μmol H2 for 6 h, which is 1.27 times that generated from the mechanically mixed system of CdS-DETA NSs and [(tpy-CH=NR)2 Ni]Cl2 (III) under otherwise identical conditions. 27573187 2 15 theme imine 409:413 arg1 -CH=N- 421:426 -CH=N- 421:426 -CH=N- 421:426 Herein, we adopt the inorganic-organic hybrid CdS-DETA NSs (DETA=diethylenetriamine, NSs=nanosheets) as initial matrix to successfully construct an imine bond (-CH=N-) linked heterogeneous dyad [CdS-N=CH-Ni] through the condensation reaction between the amino groups of CdS-DETA and the aldehyde group of the water reduction molecular catalyst, [(tpy-CHO)2 Ni]Cl2 (tpy=terpyridine). 27573187 2 15 theme imine 409:413 arg1 bond 415:418 an imine bond 406:418 an imine bond (-CH=N-) linked heterogeneous dyad [CdS-N=CH-Ni] through the condensation reaction between the amino groups of CdS-DETA and the aldehyde group of the water reduction molecular catalyst, [(tpy-CHO)2 Ni]Cl2 (tpy=terpyridine) 406:641 Herein, we adopt the inorganic-organic hybrid CdS-DETA NSs (DETA=diethylenetriamine, NSs=nanosheets) as initial matrix to successfully construct an imine bond (-CH=N-) linked heterogeneous dyad [CdS-N=CH-Ni] through the condensation reaction between the amino groups of CdS-DETA and the aldehyde group of the water reduction molecular catalyst, [(tpy-CHO)2 Ni]Cl2 (tpy=terpyridine). 27573187 0 16 theme Heterogeneous 2:14 arg1 Dyad 50:53 A Heterogeneous Photocatalytic Hydrogen Evolution Dyad 0:53 A Heterogeneous Photocatalytic Hydrogen Evolution Dyad: [(tpy. 0:61 A Heterogeneous Photocatalytic Hydrogen Evolution Dyad: [(tpy. 27573187 3 17 from frequency 754:762 arg1 26 h 799:802 26 h 799:802 26 h 799:802 The [CdS-N=CH-Ni] enables a turnover number (TON) of about 43 815 versus Ni catalysts and an initial turnover frequency (TOF) of approximately 0.47 s-1 in 26 h under visible-light irradiation (λ>420 nm). 27573187 5 18 theme considerable 970:981 arg1 H2 1028:1029 507.1±27 μmol H2 1014:1029 507.1±27 μmol H2 for 6 h 1014:1037 Under optical conditions, the [CdS-N=CH-Ni] can achieve a considerable amount of hydrogen production, 507.1±27 μmol H2 for 6 h, which is 1.27 times that generated from the mechanically mixed system of CdS-DETA NSs and [(tpy-CH=NR)2 Ni]Cl2 (III) under otherwise identical conditions. 27573187 5 18 theme considerable 970:981 arg1 amount 983:988 a considerable amount 968:988 a considerable amount of hydrogen production, 507.1±27 μmol H2 for 6 h, which is 1.27 times that generated from the mechanically mixed system of CdS-DETA NSs and [(tpy-CH=NR)2 Ni]Cl2 (III) under otherwise identical conditions 968:1192 Under optical conditions, the [CdS-N=CH-Ni] can achieve a considerable amount of hydrogen production, 507.1±27 μmol H2 for 6 h, which is 1.27 times that generated from the mechanically mixed system of CdS-DETA NSs and [(tpy-CH=NR)2 Ni]Cl2 (III) under otherwise identical conditions. 27573187 5 18 theme considerable 970:981 arg1 production 1002:1011 hydrogen production 993:1011 hydrogen production 993:1011 Under optical conditions, the [CdS-N=CH-Ni] can achieve a considerable amount of hydrogen production, 507.1±27 μmol H2 for 6 h, which is 1.27 times that generated from the mechanically mixed system of CdS-DETA NSs and [(tpy-CH=NR)2 Ni]Cl2 (III) under otherwise identical conditions. 27573187 3 19 from 26 h 799:802 arg1 TON 689:691 TON 689:691 TON 689:691 The [CdS-N=CH-Ni] enables a turnover number (TON) of about 43 815 versus Ni catalysts and an initial turnover frequency (TOF) of approximately 0.47 s-1 in 26 h under visible-light irradiation (λ>420 nm). 27573187 3 19 from 26 h 799:802 arg1 number 681:686 a turnover number 670:686 a turnover number (TON) of about 43 815 versus Ni catalysts 670:728 The [CdS-N=CH-Ni] enables a turnover number (TON) of about 43 815 versus Ni catalysts and an initial turnover frequency (TOF) of approximately 0.47 s-1 in 26 h under visible-light irradiation (λ>420 nm). 27573187 3 19 from 26 h 799:802 arg1 frequency 754:762 an initial turnover frequency 734:762 an initial turnover frequency (TOF) of approximately 0.47 s-1 in 26 h 734:802 The [CdS-N=CH-Ni] enables a turnover number (TON) of about 43 815 versus Ni catalysts and an initial turnover frequency (TOF) of approximately 0.47 s-1 in 26 h under visible-light irradiation (λ>420 nm). 27573187 3 19 from 26 h 799:802 arg1 TOF 765:767 TOF 765:767 TOF 765:767 The [CdS-N=CH-Ni] enables a turnover number (TON) of about 43 815 versus Ni catalysts and an initial turnover frequency (TOF) of approximately 0.47 s-1 in 26 h under visible-light irradiation (λ>420 nm). 27573187 1 20 theme semiconductor 182:194 arg1 photosensitizer 196:210 a semiconductor photosensitizer 180:210 a semiconductor photosensitizer through a bridging ligand 180:236 The development of an artificial heterogeneous dyad by covalently anchoring a hydrogen-evolving molecule catalyst to a semiconductor photosensitizer through a bridging ligand is highly challenging. 27573187 0 21 theme Hydrogen 31:38 arg1 Dyad 50:53 A Heterogeneous Photocatalytic Hydrogen Evolution Dyad 0:53 A Heterogeneous Photocatalytic Hydrogen Evolution Dyad: [(tpy. 0:61 A Heterogeneous Photocatalytic Hydrogen Evolution Dyad: [(tpy. 27573187 3 22 theme Ni 717:718 arg1 catalysts 720:728 about 43 815 versus Ni catalysts 697:728 about 43 815 versus Ni catalysts 697:728 The [CdS-N=CH-Ni] enables a turnover number (TON) of about 43 815 versus Ni catalysts and an initial turnover frequency (TOF) of approximately 0.47 s-1 in 26 h under visible-light irradiation (λ>420 nm). 27573187 6 23 theme TON 1212:1214 arg1 value 1216:1220 its TON value 1208:1220 its TON value based on Ni species 1208:1240 Furthermore, its TON value based on Ni species is also higher than that of the mixed system of CdS-DETA and III. 27573187 5 24 theme identical 1173:1181 arg1 conditions 1183:1192 otherwise identical conditions 1163:1192 otherwise identical conditions 1163:1192 Under optical conditions, the [CdS-N=CH-Ni] can achieve a considerable amount of hydrogen production, 507.1±27 μmol H2 for 6 h, which is 1.27 times that generated from the mechanically mixed system of CdS-DETA NSs and [(tpy-CH=NR)2 Ni]Cl2 (III) under otherwise identical conditions. 27573187 2 25 theme linked 429:434 arg1 [CdS-N=CH-Ni 455:466 linked heterogeneous dyad [CdS-N=CH-Ni 429:466 linked heterogeneous dyad [CdS-N=CH-Ni 429:466 Herein, we adopt the inorganic-organic hybrid CdS-DETA NSs (DETA=diethylenetriamine, NSs=nanosheets) as initial matrix to successfully construct an imine bond (-CH=N-) linked heterogeneous dyad [CdS-N=CH-Ni] through the condensation reaction between the amino groups of CdS-DETA and the aldehyde group of the water reduction molecular catalyst, [(tpy-CHO)2 Ni]Cl2 (tpy=terpyridine). 27573187 0 26 theme Photocatalytic 16:29 arg1 Dyad 50:53 A Heterogeneous Photocatalytic Hydrogen Evolution Dyad 0:53 A Heterogeneous Photocatalytic Hydrogen Evolution Dyad: [(tpy. 0:61 A Heterogeneous Photocatalytic Hydrogen Evolution Dyad: [(tpy. 27573187 5 27 theme mixed 1097:1101 arg1 system 1103:1108 the mechanically mixed system 1080:1108 the mechanically mixed system of CdS-DETA NSs and [(tpy-CH=NR)2 Ni]Cl2 (III) 1080:1155 Under optical conditions, the [CdS-N=CH-Ni] can achieve a considerable amount of hydrogen production, 507.1±27 μmol H2 for 6 h, which is 1.27 times that generated from the mechanically mixed system of CdS-DETA NSs and [(tpy-CH=NR)2 Ni]Cl2 (III) under otherwise identical conditions. 27573187 5 28 dep tpy-CH=NR 1132:1140 arg1 Ni 1144:1145 2 Ni 1142:1145 2 Ni 1142:1145 Under optical conditions, the [CdS-N=CH-Ni] can achieve a considerable amount of hydrogen production, 507.1±27 μmol H2 for 6 h, which is 1.27 times that generated from the mechanically mixed system of CdS-DETA NSs and [(tpy-CH=NR)2 Ni]Cl2 (III) under otherwise identical conditions. 27573187 2 29 theme CdS-DETA 307:314 arg1 NSs 316:318 the inorganic-organic hybrid CdS-DETA NSs 278:318 the inorganic-organic hybrid CdS-DETA NSs (DETA=diethylenetriamine, NSs=nanosheets) as initial matrix to successfully construct an imine bond (-CH=N-) linked heterogeneous dyad [CdS-N=CH-Ni] through the condensation reaction between the amino groups of CdS-DETA and the aldehyde group of the water reduction molecular catalyst, [(tpy-CHO)2 Ni]Cl2 (tpy=terpyridine) 278:641 Herein, we adopt the inorganic-organic hybrid CdS-DETA NSs (DETA=diethylenetriamine, NSs=nanosheets) as initial matrix to successfully construct an imine bond (-CH=N-) linked heterogeneous dyad [CdS-N=CH-Ni] through the condensation reaction between the amino groups of CdS-DETA and the aldehyde group of the water reduction molecular catalyst, [(tpy-CHO)2 Ni]Cl2 (tpy=terpyridine). 27573187 2 30 dep -CH=N- 421:426 arg1 [CdS-N=CH-Ni 455:466 linked heterogeneous dyad [CdS-N=CH-Ni 429:466 linked heterogeneous dyad [CdS-N=CH-Ni 429:466 Herein, we adopt the inorganic-organic hybrid CdS-DETA NSs (DETA=diethylenetriamine, NSs=nanosheets) as initial matrix to successfully construct an imine bond (-CH=N-) linked heterogeneous dyad [CdS-N=CH-Ni] through the condensation reaction between the amino groups of CdS-DETA and the aldehyde group of the water reduction molecular catalyst, [(tpy-CHO)2 Ni]Cl2 (tpy=terpyridine). 27573187 0 31 theme Evolution 40:48 arg1 Dyad 50:53 A Heterogeneous Photocatalytic Hydrogen Evolution Dyad 0:53 A Heterogeneous Photocatalytic Hydrogen Evolution Dyad: [(tpy. 0:61 A Heterogeneous Photocatalytic Hydrogen Evolution Dyad: [(tpy. 27573187 2 32 theme aldehyde 548:555 arg1 CdS-DETA 531:538 CdS-DETA 531:538 CdS-DETA 531:538 Herein, we adopt the inorganic-organic hybrid CdS-DETA NSs (DETA=diethylenetriamine, NSs=nanosheets) as initial matrix to successfully construct an imine bond (-CH=N-) linked heterogeneous dyad [CdS-N=CH-Ni] through the condensation reaction between the amino groups of CdS-DETA and the aldehyde group of the water reduction molecular catalyst, [(tpy-CHO)2 Ni]Cl2 (tpy=terpyridine). 27573187 2 32 theme aldehyde 548:555 arg1 Cl2 621:623 [(tpy-CHO)2 Ni]Cl2 606:623 [(tpy-CHO)2 Ni]Cl2 (tpy=terpyridine) 606:641 Herein, we adopt the inorganic-organic hybrid CdS-DETA NSs (DETA=diethylenetriamine, NSs=nanosheets) as initial matrix to successfully construct an imine bond (-CH=N-) linked heterogeneous dyad [CdS-N=CH-Ni] through the condensation reaction between the amino groups of CdS-DETA and the aldehyde group of the water reduction molecular catalyst, [(tpy-CHO)2 Ni]Cl2 (tpy=terpyridine). 27573187 2 32 theme aldehyde 548:555 arg1 group 557:561 the aldehyde group 544:561 the aldehyde group of the water reduction molecular catalyst, [(tpy-CHO)2 Ni]Cl2 (tpy=terpyridine) 544:641 Herein, we adopt the inorganic-organic hybrid CdS-DETA NSs (DETA=diethylenetriamine, NSs=nanosheets) as initial matrix to successfully construct an imine bond (-CH=N-) linked heterogeneous dyad [CdS-N=CH-Ni] through the condensation reaction between the amino groups of CdS-DETA and the aldehyde group of the water reduction molecular catalyst, [(tpy-CHO)2 Ni]Cl2 (tpy=terpyridine). 27573187 2 32 theme aldehyde 548:555 arg1 catalyst 596:603 the water reduction molecular catalyst 566:603 the water reduction molecular catalyst 566:603 Herein, we adopt the inorganic-organic hybrid CdS-DETA NSs (DETA=diethylenetriamine, NSs=nanosheets) as initial matrix to successfully construct an imine bond (-CH=N-) linked heterogeneous dyad [CdS-N=CH-Ni] through the condensation reaction between the amino groups of CdS-DETA and the aldehyde group of the water reduction molecular catalyst, [(tpy-CHO)2 Ni]Cl2 (tpy=terpyridine). 27573187 5 33 theme hydrogen 993:1000 arg1 H2 1028:1029 507.1±27 μmol H2 1014:1029 507.1±27 μmol H2 for 6 h 1014:1037 Under optical conditions, the [CdS-N=CH-Ni] can achieve a considerable amount of hydrogen production, 507.1±27 μmol H2 for 6 h, which is 1.27 times that generated from the mechanically mixed system of CdS-DETA NSs and [(tpy-CH=NR)2 Ni]Cl2 (III) under otherwise identical conditions. 27573187 5 33 theme hydrogen 993:1000 arg1 production 1002:1011 hydrogen production 993:1011 hydrogen production 993:1011 Under optical conditions, the [CdS-N=CH-Ni] can achieve a considerable amount of hydrogen production, 507.1±27 μmol H2 for 6 h, which is 1.27 times that generated from the mechanically mixed system of CdS-DETA NSs and [(tpy-CH=NR)2 Ni]Cl2 (III) under otherwise identical conditions. 27573187 2 34 theme dyad 450:453 arg1 [CdS-N=CH-Ni 455:466 linked heterogeneous dyad [CdS-N=CH-Ni 429:466 linked heterogeneous dyad [CdS-N=CH-Ni 429:466 Herein, we adopt the inorganic-organic hybrid CdS-DETA NSs (DETA=diethylenetriamine, NSs=nanosheets) as initial matrix to successfully construct an imine bond (-CH=N-) linked heterogeneous dyad [CdS-N=CH-Ni] through the condensation reaction between the amino groups of CdS-DETA and the aldehyde group of the water reduction molecular catalyst, [(tpy-CHO)2 Ni]Cl2 (tpy=terpyridine). 27573187 1 35 theme bridging 222:229 arg1 ligand 231:236 a bridging ligand 220:236 a bridging ligand 220:236 The development of an artificial heterogeneous dyad by covalently anchoring a hydrogen-evolving molecule catalyst to a semiconductor photosensitizer through a bridging ligand is highly challenging. 27573187 2 36 dep tpy-CHO 608:614 arg1 Ni 618:619 2 Ni 616:619 2 Ni 616:619 Herein, we adopt the inorganic-organic hybrid CdS-DETA NSs (DETA=diethylenetriamine, NSs=nanosheets) as initial matrix to successfully construct an imine bond (-CH=N-) linked heterogeneous dyad [CdS-N=CH-Ni] through the condensation reaction between the amino groups of CdS-DETA and the aldehyde group of the water reduction molecular catalyst, [(tpy-CHO)2 Ni]Cl2 (tpy=terpyridine). 27573187 3 37 theme initial 737:743 arg1 TOF 765:767 TOF 765:767 TOF 765:767 The [CdS-N=CH-Ni] enables a turnover number (TON) of about 43 815 versus Ni catalysts and an initial turnover frequency (TOF) of approximately 0.47 s-1 in 26 h under visible-light irradiation (λ>420 nm). 27573187 3 37 theme initial 737:743 arg1 frequency 754:762 an initial turnover frequency 734:762 an initial turnover frequency (TOF) of approximately 0.47 s-1 in 26 h 734:802 The [CdS-N=CH-Ni] enables a turnover number (TON) of about 43 815 versus Ni catalysts and an initial turnover frequency (TOF) of approximately 0.47 s-1 in 26 h under visible-light irradiation (λ>420 nm). 27573187 2 38 theme catalyst 596:603 arg1 CdS-DETA 531:538 CdS-DETA 531:538 CdS-DETA 531:538 Herein, we adopt the inorganic-organic hybrid CdS-DETA NSs (DETA=diethylenetriamine, NSs=nanosheets) as initial matrix to successfully construct an imine bond (-CH=N-) linked heterogeneous dyad [CdS-N=CH-Ni] through the condensation reaction between the amino groups of CdS-DETA and the aldehyde group of the water reduction molecular catalyst, [(tpy-CHO)2 Ni]Cl2 (tpy=terpyridine). 27573187 2 38 theme catalyst 596:603 arg1 Cl2 621:623 [(tpy-CHO)2 Ni]Cl2 606:623 [(tpy-CHO)2 Ni]Cl2 (tpy=terpyridine) 606:641 Herein, we adopt the inorganic-organic hybrid CdS-DETA NSs (DETA=diethylenetriamine, NSs=nanosheets) as initial matrix to successfully construct an imine bond (-CH=N-) linked heterogeneous dyad [CdS-N=CH-Ni] through the condensation reaction between the amino groups of CdS-DETA and the aldehyde group of the water reduction molecular catalyst, [(tpy-CHO)2 Ni]Cl2 (tpy=terpyridine). 27573187 2 38 theme catalyst 596:603 arg1 groups 521:526 the amino groups 511:526 the amino groups of CdS-DETA 511:538 Herein, we adopt the inorganic-organic hybrid CdS-DETA NSs (DETA=diethylenetriamine, NSs=nanosheets) as initial matrix to successfully construct an imine bond (-CH=N-) linked heterogeneous dyad [CdS-N=CH-Ni] through the condensation reaction between the amino groups of CdS-DETA and the aldehyde group of the water reduction molecular catalyst, [(tpy-CHO)2 Ni]Cl2 (tpy=terpyridine). 27573187 2 38 theme catalyst 596:603 arg1 group 557:561 the aldehyde group 544:561 the aldehyde group of the water reduction molecular catalyst, [(tpy-CHO)2 Ni]Cl2 (tpy=terpyridine) 544:641 Herein, we adopt the inorganic-organic hybrid CdS-DETA NSs (DETA=diethylenetriamine, NSs=nanosheets) as initial matrix to successfully construct an imine bond (-CH=N-) linked heterogeneous dyad [CdS-N=CH-Ni] through the condensation reaction between the amino groups of CdS-DETA and the aldehyde group of the water reduction molecular catalyst, [(tpy-CHO)2 Ni]Cl2 (tpy=terpyridine). 27573187 2 38 theme catalyst 596:603 arg1 catalyst 596:603 the water reduction molecular catalyst 566:603 the water reduction molecular catalyst 566:603 Herein, we adopt the inorganic-organic hybrid CdS-DETA NSs (DETA=diethylenetriamine, NSs=nanosheets) as initial matrix to successfully construct an imine bond (-CH=N-) linked heterogeneous dyad [CdS-N=CH-Ni] through the condensation reaction between the amino groups of CdS-DETA and the aldehyde group of the water reduction molecular catalyst, [(tpy-CHO)2 Ni]Cl2 (tpy=terpyridine). 27573187 4 39 theme   898:898 arg1 % 899:899 (9.9±0.8) % 889:899 (9.9±0.8) % 889:899 The apparent quantum yield (AQY) reaches (9.9±0.8) % at 420 nm. 27573187 0 40 dep Dyad 50:53 arg1 tpy 58:60 tpy 58:60 tpy 58:60 A Heterogeneous Photocatalytic Hydrogen Evolution Dyad: [(tpy. 27573187 4 41 theme quantum 861:867 arg1 AQY 876:878 AQY 876:878 AQY 876:878 The apparent quantum yield (AQY) reaches (9.9±0.8) % at 420 nm. 27573187 4 41 theme quantum 861:867 arg1 yield 869:873 The apparent quantum yield 848:873 The apparent quantum yield (AQY) 848:879 The apparent quantum yield (AQY) reaches (9.9±0.8) % at 420 nm. 27573187 1 42 theme heterogeneous 96:108 arg1 dyad 110:113 an artificial heterogeneous dyad 82:113 an artificial heterogeneous dyad 82:113 The development of an artificial heterogeneous dyad by covalently anchoring a hydrogen-evolving molecule catalyst to a semiconductor photosensitizer through a bridging ligand is highly challenging. 27573187 3 43 from number 681:686 arg1 26 h 799:802 26 h 799:802 26 h 799:802 The [CdS-N=CH-Ni] enables a turnover number (TON) of about 43 815 versus Ni catalysts and an initial turnover frequency (TOF) of approximately 0.47 s-1 in 26 h under visible-light irradiation (λ>420 nm). 27573187 3 44 theme catalysts 720:728 arg1 TON 689:691 TON 689:691 TON 689:691 The [CdS-N=CH-Ni] enables a turnover number (TON) of about 43 815 versus Ni catalysts and an initial turnover frequency (TOF) of approximately 0.47 s-1 in 26 h under visible-light irradiation (λ>420 nm). 27573187 3 44 theme catalysts 720:728 arg1 number 681:686 a turnover number 670:686 a turnover number (TON) of about 43 815 versus Ni catalysts 670:728 The [CdS-N=CH-Ni] enables a turnover number (TON) of about 43 815 versus Ni catalysts and an initial turnover frequency (TOF) of approximately 0.47 s-1 in 26 h under visible-light irradiation (λ>420 nm). 27573187 3 44 theme catalysts 720:728 arg1 frequency 754:762 an initial turnover frequency 734:762 an initial turnover frequency (TOF) of approximately 0.47 s-1 in 26 h 734:802 The [CdS-N=CH-Ni] enables a turnover number (TON) of about 43 815 versus Ni catalysts and an initial turnover frequency (TOF) of approximately 0.47 s-1 in 26 h under visible-light irradiation (λ>420 nm). 27573187 3 44 theme catalysts 720:728 arg1 TOF 765:767 TOF 765:767 TOF 765:767 The [CdS-N=CH-Ni] enables a turnover number (TON) of about 43 815 versus Ni catalysts and an initial turnover frequency (TOF) of approximately 0.47 s-1 in 26 h under visible-light irradiation (λ>420 nm). 27573187 2 45 theme molecular 586:594 arg1 Cl2 621:623 [(tpy-CHO)2 Ni]Cl2 606:623 [(tpy-CHO)2 Ni]Cl2 (tpy=terpyridine) 606:641 Herein, we adopt the inorganic-organic hybrid CdS-DETA NSs (DETA=diethylenetriamine, NSs=nanosheets) as initial matrix to successfully construct an imine bond (-CH=N-) linked heterogeneous dyad [CdS-N=CH-Ni] through the condensation reaction between the amino groups of CdS-DETA and the aldehyde group of the water reduction molecular catalyst, [(tpy-CHO)2 Ni]Cl2 (tpy=terpyridine). 27573187 2 45 theme molecular 586:594 arg1 catalyst 596:603 the water reduction molecular catalyst 566:603 the water reduction molecular catalyst 566:603 Herein, we adopt the inorganic-organic hybrid CdS-DETA NSs (DETA=diethylenetriamine, NSs=nanosheets) as initial matrix to successfully construct an imine bond (-CH=N-) linked heterogeneous dyad [CdS-N=CH-Ni] through the condensation reaction between the amino groups of CdS-DETA and the aldehyde group of the water reduction molecular catalyst, [(tpy-CHO)2 Ni]Cl2 (tpy=terpyridine). 27573187 1 46 theme dyad 110:113 arg1 development 67:77 The development 63:77 The development of an artificial heterogeneous dyad by covalently anchoring a hydrogen-evolving molecule catalyst to a semiconductor photosensitizer through a bridging ligand 63:236 The development of an artificial heterogeneous dyad by covalently anchoring a hydrogen-evolving molecule catalyst to a semiconductor photosensitizer through a bridging ligand is highly challenging. 27573187 2 47 theme reduction 576:584 arg1 Cl2 621:623 [(tpy-CHO)2 Ni]Cl2 606:623 [(tpy-CHO)2 Ni]Cl2 (tpy=terpyridine) 606:641 Herein, we adopt the inorganic-organic hybrid CdS-DETA NSs (DETA=diethylenetriamine, NSs=nanosheets) as initial matrix to successfully construct an imine bond (-CH=N-) linked heterogeneous dyad [CdS-N=CH-Ni] through the condensation reaction between the amino groups of CdS-DETA and the aldehyde group of the water reduction molecular catalyst, [(tpy-CHO)2 Ni]Cl2 (tpy=terpyridine). 27573187 2 47 theme reduction 576:584 arg1 catalyst 596:603 the water reduction molecular catalyst 566:603 the water reduction molecular catalyst 566:603 Herein, we adopt the inorganic-organic hybrid CdS-DETA NSs (DETA=diethylenetriamine, NSs=nanosheets) as initial matrix to successfully construct an imine bond (-CH=N-) linked heterogeneous dyad [CdS-N=CH-Ni] through the condensation reaction between the amino groups of CdS-DETA and the aldehyde group of the water reduction molecular catalyst, [(tpy-CHO)2 Ni]Cl2 (tpy=terpyridine). 27573187 3 48 theme visible-light 810:822 arg1 λ>420 nm 837:844 λ>420 nm 837:844 λ>420 nm 837:844 The [CdS-N=CH-Ni] enables a turnover number (TON) of about 43 815 versus Ni catalysts and an initial turnover frequency (TOF) of approximately 0.47 s-1 in 26 h under visible-light irradiation (λ>420 nm). 27573187 3 48 theme visible-light 810:822 arg1 irradiation 824:834 visible-light irradiation 810:834 visible-light irradiation (λ>420 nm) 810:845 The [CdS-N=CH-Ni] enables a turnover number (TON) of about 43 815 versus Ni catalysts and an initial turnover frequency (TOF) of approximately 0.47 s-1 in 26 h under visible-light irradiation (λ>420 nm). 27573187 2 49 theme water 570:574 arg1 Cl2 621:623 [(tpy-CHO)2 Ni]Cl2 606:623 [(tpy-CHO)2 Ni]Cl2 (tpy=terpyridine) 606:641 Herein, we adopt the inorganic-organic hybrid CdS-DETA NSs (DETA=diethylenetriamine, NSs=nanosheets) as initial matrix to successfully construct an imine bond (-CH=N-) linked heterogeneous dyad [CdS-N=CH-Ni] through the condensation reaction between the amino groups of CdS-DETA and the aldehyde group of the water reduction molecular catalyst, [(tpy-CHO)2 Ni]Cl2 (tpy=terpyridine). 27573187 2 49 theme water 570:574 arg1 catalyst 596:603 the water reduction molecular catalyst 566:603 the water reduction molecular catalyst 566:603 Herein, we adopt the inorganic-organic hybrid CdS-DETA NSs (DETA=diethylenetriamine, NSs=nanosheets) as initial matrix to successfully construct an imine bond (-CH=N-) linked heterogeneous dyad [CdS-N=CH-Ni] through the condensation reaction between the amino groups of CdS-DETA and the aldehyde group of the water reduction molecular catalyst, [(tpy-CHO)2 Ni]Cl2 (tpy=terpyridine). 27573187 2 50 link linked 429:434 arg1 [CdS-N=CH-Ni 455:466 linked heterogeneous dyad [CdS-N=CH-Ni 429:466 linked heterogeneous dyad [CdS-N=CH-Ni 429:466 Herein, we adopt the inorganic-organic hybrid CdS-DETA NSs (DETA=diethylenetriamine, NSs=nanosheets) as initial matrix to successfully construct an imine bond (-CH=N-) linked heterogeneous dyad [CdS-N=CH-Ni] through the condensation reaction between the amino groups of CdS-DETA and the aldehyde group of the water reduction molecular catalyst, [(tpy-CHO)2 Ni]Cl2 (tpy=terpyridine). 27573187 2 51 theme condensation 481:492 arg1 reaction 494:501 the condensation reaction 477:501 the condensation reaction 477:501 Herein, we adopt the inorganic-organic hybrid CdS-DETA NSs (DETA=diethylenetriamine, NSs=nanosheets) as initial matrix to successfully construct an imine bond (-CH=N-) linked heterogeneous dyad [CdS-N=CH-Ni] through the condensation reaction between the amino groups of CdS-DETA and the aldehyde group of the water reduction molecular catalyst, [(tpy-CHO)2 Ni]Cl2 (tpy=terpyridine). 27573187 6 52 theme mixed 1274:1278 arg1 system 1280:1285 the mixed system 1270:1285 the mixed system of CdS-DETA and III 1270:1305 Furthermore, its TON value based on Ni species is also higher than that of the mixed system of CdS-DETA and III. 27573187 5 53 theme Cl2 1147:1149 arg1 system 1103:1108 the mechanically mixed system 1080:1108 the mechanically mixed system of CdS-DETA NSs and [(tpy-CH=NR)2 Ni]Cl2 (III) 1080:1155 Under optical conditions, the [CdS-N=CH-Ni] can achieve a considerable amount of hydrogen production, 507.1±27 μmol H2 for 6 h, which is 1.27 times that generated from the mechanically mixed system of CdS-DETA NSs and [(tpy-CH=NR)2 Ni]Cl2 (III) under otherwise identical conditions. 27573187 5 54 theme optical 918:924 arg1 conditions 926:935 optical conditions 918:935 optical conditions 918:935 Under optical conditions, the [CdS-N=CH-Ni] can achieve a considerable amount of hydrogen production, 507.1±27 μmol H2 for 6 h, which is 1.27 times that generated from the mechanically mixed system of CdS-DETA NSs and [(tpy-CH=NR)2 Ni]Cl2 (III) under otherwise identical conditions. 27573187 3 55 from 0.47 s-1 787:794 arg1 26 h 799:802 26 h 799:802 26 h 799:802 The [CdS-N=CH-Ni] enables a turnover number (TON) of about 43 815 versus Ni catalysts and an initial turnover frequency (TOF) of approximately 0.47 s-1 in 26 h under visible-light irradiation (λ>420 nm). 27573187 3 56 theme turnover 745:752 arg1 TOF 765:767 TOF 765:767 TOF 765:767 The [CdS-N=CH-Ni] enables a turnover number (TON) of about 43 815 versus Ni catalysts and an initial turnover frequency (TOF) of approximately 0.47 s-1 in 26 h under visible-light irradiation (λ>420 nm). 27573187 3 56 theme turnover 745:752 arg1 frequency 754:762 an initial turnover frequency 734:762 an initial turnover frequency (TOF) of approximately 0.47 s-1 in 26 h 734:802 The [CdS-N=CH-Ni] enables a turnover number (TON) of about 43 815 versus Ni catalysts and an initial turnover frequency (TOF) of approximately 0.47 s-1 in 26 h under visible-light irradiation (λ>420 nm). 27573187 2 57 theme amino 515:519 arg1 CdS-DETA 531:538 CdS-DETA 531:538 CdS-DETA 531:538 Herein, we adopt the inorganic-organic hybrid CdS-DETA NSs (DETA=diethylenetriamine, NSs=nanosheets) as initial matrix to successfully construct an imine bond (-CH=N-) linked heterogeneous dyad [CdS-N=CH-Ni] through the condensation reaction between the amino groups of CdS-DETA and the aldehyde group of the water reduction molecular catalyst, [(tpy-CHO)2 Ni]Cl2 (tpy=terpyridine). 27573187 2 57 theme amino 515:519 arg1 Cl2 621:623 [(tpy-CHO)2 Ni]Cl2 606:623 [(tpy-CHO)2 Ni]Cl2 (tpy=terpyridine) 606:641 Herein, we adopt the inorganic-organic hybrid CdS-DETA NSs (DETA=diethylenetriamine, NSs=nanosheets) as initial matrix to successfully construct an imine bond (-CH=N-) linked heterogeneous dyad [CdS-N=CH-Ni] through the condensation reaction between the amino groups of CdS-DETA and the aldehyde group of the water reduction molecular catalyst, [(tpy-CHO)2 Ni]Cl2 (tpy=terpyridine). 27573187 2 57 theme amino 515:519 arg1 groups 521:526 the amino groups 511:526 the amino groups of CdS-DETA 511:538 Herein, we adopt the inorganic-organic hybrid CdS-DETA NSs (DETA=diethylenetriamine, NSs=nanosheets) as initial matrix to successfully construct an imine bond (-CH=N-) linked heterogeneous dyad [CdS-N=CH-Ni] through the condensation reaction between the amino groups of CdS-DETA and the aldehyde group of the water reduction molecular catalyst, [(tpy-CHO)2 Ni]Cl2 (tpy=terpyridine). 27573187 2 57 theme amino 515:519 arg1 catalyst 596:603 the water reduction molecular catalyst 566:603 the water reduction molecular catalyst 566:603 Herein, we adopt the inorganic-organic hybrid CdS-DETA NSs (DETA=diethylenetriamine, NSs=nanosheets) as initial matrix to successfully construct an imine bond (-CH=N-) linked heterogeneous dyad [CdS-N=CH-Ni] through the condensation reaction between the amino groups of CdS-DETA and the aldehyde group of the water reduction molecular catalyst, [(tpy-CHO)2 Ni]Cl2 (tpy=terpyridine). 27573187 3 58 theme turnover 672:679 arg1 TON 689:691 TON 689:691 TON 689:691 The [CdS-N=CH-Ni] enables a turnover number (TON) of about 43 815 versus Ni catalysts and an initial turnover frequency (TOF) of approximately 0.47 s-1 in 26 h under visible-light irradiation (λ>420 nm). 27573187 3 58 theme turnover 672:679 arg1 number 681:686 a turnover number 670:686 a turnover number (TON) of about 43 815 versus Ni catalysts 670:728 The [CdS-N=CH-Ni] enables a turnover number (TON) of about 43 815 versus Ni catalysts and an initial turnover frequency (TOF) of approximately 0.47 s-1 in 26 h under visible-light irradiation (λ>420 nm). 27573187 2 59 theme heterogeneous 436:448 arg1 [CdS-N=CH-Ni 455:466 linked heterogeneous dyad [CdS-N=CH-Ni 429:466 linked heterogeneous dyad [CdS-N=CH-Ni 429:466 Herein, we adopt the inorganic-organic hybrid CdS-DETA NSs (DETA=diethylenetriamine, NSs=nanosheets) as initial matrix to successfully construct an imine bond (-CH=N-) linked heterogeneous dyad [CdS-N=CH-Ni] through the condensation reaction between the amino groups of CdS-DETA and the aldehyde group of the water reduction molecular catalyst, [(tpy-CHO)2 Ni]Cl2 (tpy=terpyridine). 27573187 6 60 theme CdS-DETA 1290:1297 arg1 system 1280:1285 the mixed system 1270:1285 the mixed system of CdS-DETA and III 1270:1305 Furthermore, its TON value based on Ni species is also higher than that of the mixed system of CdS-DETA and III. 26036200 4 0 theme cell 951:954 arg1 media 964:968 harvested cell culture media 941:968 harvested cell culture media 941:968 When model scFv-Fc protein was engineered to multimerize, by appending the secretory tailpiece (stp) of human immunoglobulin μ-chain to the C terminus, the resulting oligomeric scFv-Fc-stp protein acquired two unexpected properties: the induction of a morular cell phenotype during protein biosynthesis and the cryoprecipitation of secreted proteins in harvested cell culture media. 26036200 7 1 theme N-linked 1347:1354 arg1 motif 1370:1374 the N-linked glycosylation motif 1343:1374 the N-linked glycosylation motif 1343:1374 Disruption of the N-linked glycosylation motif in the stp region enhanced morular phenotype propensity but reduced protein secretion. 26036200 2 2 theme general 399:405 arg1 lack 407:410 a general lack 397:410 a general lack of suitable experimental systems 397:443 However, the biochemical basis of such cryoglobulin behaviors is not well understood because of a general lack of suitable experimental systems. 26036200 9 3 theme Noncovalent 1667:1677 arg1 interactions 1695:1706 Noncovalent protein-protein interactions 1667:1706 Noncovalent protein-protein interactions between scFv-Fc-stp chains 1667:1733 Noncovalent protein-protein interactions between scFv-Fc-stp chains sufficiently established a basis for LLPS induction. 26036200 6 4 theme protein 1289:1295 arg1 oligomerization 1297:1311 covalent protein oligomerization 1280:1311 covalent protein oligomerization induced by stp 1280:1326 Mutagenesis approaches revealed that these two phenomena were independent of covalent protein oligomerization induced by stp. 26036200 4 5 theme secretory 663:671 arg1 stp 684:686 stp 684:686 stp 684:686 When model scFv-Fc protein was engineered to multimerize, by appending the secretory tailpiece (stp) of human immunoglobulin μ-chain to the C terminus, the resulting oligomeric scFv-Fc-stp protein acquired two unexpected properties: the induction of a morular cell phenotype during protein biosynthesis and the cryoprecipitation of secreted proteins in harvested cell culture media. 26036200 4 5 theme secretory 663:671 arg1 tailpiece 673:681 the secretory tailpiece 659:681 the secretory tailpiece (stp) of human immunoglobulin μ-chain to the C terminus 659:737 When model scFv-Fc protein was engineered to multimerize, by appending the secretory tailpiece (stp) of human immunoglobulin μ-chain to the C terminus, the resulting oligomeric scFv-Fc-stp protein acquired two unexpected properties: the induction of a morular cell phenotype during protein biosynthesis and the cryoprecipitation of secreted proteins in harvested cell culture media. 26036200 2 6 theme such 335:338 arg1 behaviors 353:361 such cryoglobulin behaviors 335:361 such cryoglobulin behaviors 335:361 However, the biochemical basis of such cryoglobulin behaviors is not well understood because of a general lack of suitable experimental systems. 26036200 4 7 theme secreted 920:927 arg1 proteins 929:936 secreted proteins 920:936 secreted proteins in harvested cell culture media 920:968 When model scFv-Fc protein was engineered to multimerize, by appending the secretory tailpiece (stp) of human immunoglobulin μ-chain to the C terminus, the resulting oligomeric scFv-Fc-stp protein acquired two unexpected properties: the induction of a morular cell phenotype during protein biosynthesis and the cryoprecipitation of secreted proteins in harvested cell culture media. 26036200 10 8 from protein 1935:1941 arg1 embedded 1899:1906 embedded 1899:1906 embedded 1899:1906 Morular cell phenotypes and cryoprecipitation were clearly underpinned by intrinsic physicochemical properties embedded in the overexpressed cargo protein. 26036200 7 9 link N-linked 1347:1354 arg1 motif 1370:1374 the N-linked glycosylation motif 1343:1374 the N-linked glycosylation motif 1343:1374 Disruption of the N-linked glycosylation motif in the stp region enhanced morular phenotype propensity but reduced protein secretion. 26036200 4 10 theme human 692:696 arg1 μ-chain 713:719 human immunoglobulin μ-chain 692:719 human immunoglobulin μ-chain 692:719 When model scFv-Fc protein was engineered to multimerize, by appending the secretory tailpiece (stp) of human immunoglobulin μ-chain to the C terminus, the resulting oligomeric scFv-Fc-stp protein acquired two unexpected properties: the induction of a morular cell phenotype during protein biosynthesis and the cryoprecipitation of secreted proteins in harvested cell culture media. 26036200 0 11 theme pathway 141:147 arg1 organelles 149:158 the secretory pathway organelles 127:158 the secretory pathway organelles 127:158 Overexpression of cryoglobulin-like single-chain antibody induces morular cell phenotype via liquid-liquid phase separation in the secretory pathway organelles. 26036200 5 12 theme liquid-liquid 1158:1170 arg1 LLPS 1190:1193 LLPS 1190:1193 LLPS 1190:1193 The turbidity of the culture media and the inclusion bodies that gave morular appearances were attributed to microscopic spherical protein droplet formation, a hallmark characteristic of liquid-liquid phase separation (LLPS) event. 26036200 5 12 theme liquid-liquid 1158:1170 arg1 separation 1178:1187 liquid-liquid phase separation 1158:1187 liquid-liquid phase separation (LLPS) event 1158:1200 The turbidity of the culture media and the inclusion bodies that gave morular appearances were attributed to microscopic spherical protein droplet formation, a hallmark characteristic of liquid-liquid phase separation (LLPS) event. 26036200 2 13 theme behaviors 353:361 arg1 basis 326:330 the biochemical basis 310:330 the biochemical basis of such cryoglobulin behaviors 310:361 However, the biochemical basis of such cryoglobulin behaviors is not well understood because of a general lack of suitable experimental systems. 26036200 1 14 theme lymphoproliferative 243:261 arg1 disorders 263:271 B-cell lymphoproliferative disorders 236:271 B-cell lymphoproliferative disorders 236:271 Cryoprecipitation of immunoglobulins is often reported in association with B-cell lymphoproliferative disorders and plasma cell dyscrasias. 26036200 11 15 from LLPS 2018:2021 arg1 reticulum 2042:2050 the endoplasmic reticulum 2026:2050 the endoplasmic reticulum 2026:2050 Overproduction of condensation-prone secretory proteins that culminate in LLPS in the endoplasmic reticulum therefore serves as a path to produce morular Russell body phenotype. 26036200 4 16 theme μ-chain 713:719 arg1 stp 684:686 stp 684:686 stp 684:686 When model scFv-Fc protein was engineered to multimerize, by appending the secretory tailpiece (stp) of human immunoglobulin μ-chain to the C terminus, the resulting oligomeric scFv-Fc-stp protein acquired two unexpected properties: the induction of a morular cell phenotype during protein biosynthesis and the cryoprecipitation of secreted proteins in harvested cell culture media. 26036200 4 16 theme μ-chain 713:719 arg1 tailpiece 673:681 the secretory tailpiece 659:681 the secretory tailpiece (stp) of human immunoglobulin μ-chain to the C terminus 659:737 When model scFv-Fc protein was engineered to multimerize, by appending the secretory tailpiece (stp) of human immunoglobulin μ-chain to the C terminus, the resulting oligomeric scFv-Fc-stp protein acquired two unexpected properties: the induction of a morular cell phenotype during protein biosynthesis and the cryoprecipitation of secreted proteins in harvested cell culture media. 26036200 5 17 theme separation 1178:1187 arg1 characteristic 1140:1153 characteristic 1140:1153 characteristic 1140:1153 The turbidity of the culture media and the inclusion bodies that gave morular appearances were attributed to microscopic spherical protein droplet formation, a hallmark characteristic of liquid-liquid phase separation (LLPS) event. 26036200 4 18 from cryoprecipitation 899:915 arg1 media 964:968 harvested cell culture media 941:968 harvested cell culture media 941:968 When model scFv-Fc protein was engineered to multimerize, by appending the secretory tailpiece (stp) of human immunoglobulin μ-chain to the C terminus, the resulting oligomeric scFv-Fc-stp protein acquired two unexpected properties: the induction of a morular cell phenotype during protein biosynthesis and the cryoprecipitation of secreted proteins in harvested cell culture media. 26036200 10 19 theme cell 1796:1799 arg1 phenotypes 1801:1810 Morular cell phenotypes 1788:1810 Morular cell phenotypes 1788:1810 Morular cell phenotypes and cryoprecipitation were clearly underpinned by intrinsic physicochemical properties embedded in the overexpressed cargo protein. 26036200 5 20 theme culture 992:998 arg1 media 1000:1004 the culture media 988:1004 the culture media 988:1004 The turbidity of the culture media and the inclusion bodies that gave morular appearances were attributed to microscopic spherical protein droplet formation, a hallmark characteristic of liquid-liquid phase separation (LLPS) event. 26036200 7 21 from Disruption 1329:1338 arg1 region 1387:1392 the stp region 1379:1392 the stp region 1379:1392 Disruption of the N-linked glycosylation motif in the stp region enhanced morular phenotype propensity but reduced protein secretion. 26036200 11 22 theme proteins 1991:1998 arg1 Overproduction 1944:1957 Overproduction 1944:1957 Overproduction of condensation-prone secretory proteins that culminate in LLPS in the endoplasmic reticulum 1944:2050 Overproduction of condensation-prone secretory proteins that culminate in LLPS in the endoplasmic reticulum therefore serves as a path to produce morular Russell body phenotype. 26036200 11 22 theme proteins 1991:1998 arg1 path 2074:2077 a path 2072:2077 a path to produce morular Russell body phenotype 2072:2119 Overproduction of condensation-prone secretory proteins that culminate in LLPS in the endoplasmic reticulum therefore serves as a path to produce morular Russell body phenotype. 26036200 5 23 theme characteristic 1140:1153 arg1 formation 1118:1126 microscopic spherical protein droplet formation 1080:1126 microscopic spherical protein droplet formation 1080:1126 The turbidity of the culture media and the inclusion bodies that gave morular appearances were attributed to microscopic spherical protein droplet formation, a hallmark characteristic of liquid-liquid phase separation (LLPS) event. 26036200 5 23 theme characteristic 1140:1153 arg1 hallmark 1131:1138 a hallmark 1129:1138 a hallmark characteristic of liquid-liquid phase separation (LLPS) event 1129:1200 The turbidity of the culture media and the inclusion bodies that gave morular appearances were attributed to microscopic spherical protein droplet formation, a hallmark characteristic of liquid-liquid phase separation (LLPS) event. 26036200 4 24 dep properties 809:818 arg1 properties 809:818 two unexpected properties 794:818 two unexpected properties: the induction of a morular cell phenotype during protein biosynthesis and the cryoprecipitation of secreted proteins in harvested cell culture media 794:968 When model scFv-Fc protein was engineered to multimerize, by appending the secretory tailpiece (stp) of human immunoglobulin μ-chain to the C terminus, the resulting oligomeric scFv-Fc-stp protein acquired two unexpected properties: the induction of a morular cell phenotype during protein biosynthesis and the cryoprecipitation of secreted proteins in harvested cell culture media. 26036200 4 24 dep properties 809:818 arg1 induction 825:833 the induction 821:833 the induction of a morular cell phenotype during protein biosynthesis 821:889 When model scFv-Fc protein was engineered to multimerize, by appending the secretory tailpiece (stp) of human immunoglobulin μ-chain to the C terminus, the resulting oligomeric scFv-Fc-stp protein acquired two unexpected properties: the induction of a morular cell phenotype during protein biosynthesis and the cryoprecipitation of secreted proteins in harvested cell culture media. 26036200 4 24 dep properties 809:818 arg1 cryoprecipitation 899:915 the cryoprecipitation 895:915 the cryoprecipitation of secreted proteins in harvested cell culture media 895:968 When model scFv-Fc protein was engineered to multimerize, by appending the secretory tailpiece (stp) of human immunoglobulin μ-chain to the C terminus, the resulting oligomeric scFv-Fc-stp protein acquired two unexpected properties: the induction of a morular cell phenotype during protein biosynthesis and the cryoprecipitation of secreted proteins in harvested cell culture media. 26036200 0 25 from separation 113:122 arg1 organelles 149:158 the secretory pathway organelles 127:158 the secretory pathway organelles 127:158 Overexpression of cryoglobulin-like single-chain antibody induces morular cell phenotype via liquid-liquid phase separation in the secretory pathway organelles. 26036200 10 26 theme embedded 1899:1906 arg1 properties 1888:1897 intrinsic physicochemical properties 1862:1897 intrinsic physicochemical properties embedded in the overexpressed cargo protein 1862:1941 Morular cell phenotypes and cryoprecipitation were clearly underpinned by intrinsic physicochemical properties embedded in the overexpressed cargo protein. 26036200 11 27 theme condensation-prone 1962:1979 arg1 proteins 1991:1998 condensation-prone secretory proteins 1962:1998 condensation-prone secretory proteins that culminate in LLPS in the endoplasmic reticulum 1962:2050 Overproduction of condensation-prone secretory proteins that culminate in LLPS in the endoplasmic reticulum therefore serves as a path to produce morular Russell body phenotype. 26036200 4 28 from media 964:968 arg1 properties 809:818 two unexpected properties 794:818 two unexpected properties: the induction of a morular cell phenotype during protein biosynthesis and the cryoprecipitation of secreted proteins in harvested cell culture media 794:968 When model scFv-Fc protein was engineered to multimerize, by appending the secretory tailpiece (stp) of human immunoglobulin μ-chain to the C terminus, the resulting oligomeric scFv-Fc-stp protein acquired two unexpected properties: the induction of a morular cell phenotype during protein biosynthesis and the cryoprecipitation of secreted proteins in harvested cell culture media. 26036200 4 28 from media 964:968 arg1 induction 825:833 the induction 821:833 the induction of a morular cell phenotype during protein biosynthesis 821:889 When model scFv-Fc protein was engineered to multimerize, by appending the secretory tailpiece (stp) of human immunoglobulin μ-chain to the C terminus, the resulting oligomeric scFv-Fc-stp protein acquired two unexpected properties: the induction of a morular cell phenotype during protein biosynthesis and the cryoprecipitation of secreted proteins in harvested cell culture media. 26036200 4 28 from media 964:968 arg1 cryoprecipitation 899:915 the cryoprecipitation 895:915 the cryoprecipitation of secreted proteins in harvested cell culture media 895:968 When model scFv-Fc protein was engineered to multimerize, by appending the secretory tailpiece (stp) of human immunoglobulin μ-chain to the C terminus, the resulting oligomeric scFv-Fc-stp protein acquired two unexpected properties: the induction of a morular cell phenotype during protein biosynthesis and the cryoprecipitation of secreted proteins in harvested cell culture media. 26036200 1 29 theme immunoglobulins 182:196 arg1 Cryoprecipitation 161:177 Cryoprecipitation 161:177 Cryoprecipitation of immunoglobulins 161:196 Cryoprecipitation of immunoglobulins is often reported in association with B-cell lymphoproliferative disorders and plasma cell dyscrasias. 26036200 4 30 theme oligomeric 754:763 arg1 protein 777:783 the resulting oligomeric scFv-Fc-stp protein 740:783 the resulting oligomeric scFv-Fc-stp protein 740:783 When model scFv-Fc protein was engineered to multimerize, by appending the secretory tailpiece (stp) of human immunoglobulin μ-chain to the C terminus, the resulting oligomeric scFv-Fc-stp protein acquired two unexpected properties: the induction of a morular cell phenotype during protein biosynthesis and the cryoprecipitation of secreted proteins in harvested cell culture media. 26036200 0 31 theme liquid-liquid 93:105 arg1 separation 113:122 liquid-liquid phase separation 93:122 liquid-liquid phase separation in the secretory pathway organelles 93:158 Overexpression of cryoglobulin-like single-chain antibody induces morular cell phenotype via liquid-liquid phase separation in the secretory pathway organelles. 26036200 8 32 theme disulfide 1478:1486 arg1 bonds 1488:1492 Intermolecular disulfide bonds 1463:1492 Intermolecular disulfide bonds that stabilize Fc dimers and oligomers 1463:1531 Intermolecular disulfide bonds that stabilize Fc dimers and oligomers were necessary for efficient induction of LLPS, but their simultaneous elimination could not abrogate the LLPS propensity completely. 26036200 5 33 theme morular 1041:1047 arg1 appearances 1049:1059 morular appearances 1041:1059 morular appearances 1041:1059 The turbidity of the culture media and the inclusion bodies that gave morular appearances were attributed to microscopic spherical protein droplet formation, a hallmark characteristic of liquid-liquid phase separation (LLPS) event. 26036200 4 34 theme morular 840:846 arg1 phenotype 853:861 a morular cell phenotype 838:861 a morular cell phenotype 838:861 When model scFv-Fc protein was engineered to multimerize, by appending the secretory tailpiece (stp) of human immunoglobulin μ-chain to the C terminus, the resulting oligomeric scFv-Fc-stp protein acquired two unexpected properties: the induction of a morular cell phenotype during protein biosynthesis and the cryoprecipitation of secreted proteins in harvested cell culture media. 26036200 8 35 theme Fc 1509:1510 arg1 dimers 1512:1517 Fc dimers 1509:1517 Fc dimers 1509:1517 Intermolecular disulfide bonds that stabilize Fc dimers and oligomers were necessary for efficient induction of LLPS, but their simultaneous elimination could not abrogate the LLPS propensity completely. 26036200 2 36 theme systems 437:443 arg1 lack 407:410 a general lack 397:410 a general lack of suitable experimental systems 397:443 However, the biochemical basis of such cryoglobulin behaviors is not well understood because of a general lack of suitable experimental systems. 26036200 5 37 theme inclusion 1014:1022 arg1 bodies 1024:1029 the inclusion bodies 1010:1029 the inclusion bodies that gave morular appearances 1010:1059 The turbidity of the culture media and the inclusion bodies that gave morular appearances were attributed to microscopic spherical protein droplet formation, a hallmark characteristic of liquid-liquid phase separation (LLPS) event. 26036200 7 38 theme protein 1444:1450 arg1 secretion 1452:1460 protein secretion 1444:1460 protein secretion 1444:1460 Disruption of the N-linked glycosylation motif in the stp region enhanced morular phenotype propensity but reduced protein secretion. 26036200 3 39 dep identification 466:479 arg1 the 462:464 the 462:464 the 462:464 Here, we report the identification and characterization of a single-chain antibody (scFv-Fc) that recapitulates cryoglobulin-like properties. 26036200 3 40 theme antibody 520:527 arg1 characterization 485:500 characterization 485:500 characterization 485:500 Here, we report the identification and characterization of a single-chain antibody (scFv-Fc) that recapitulates cryoglobulin-like properties. 26036200 3 40 theme antibody 520:527 arg1 identification 466:479 identification 466:479 identification 466:479 Here, we report the identification and characterization of a single-chain antibody (scFv-Fc) that recapitulates cryoglobulin-like properties. 26036200 0 41 theme cryoglobulin-like 18:34 arg1 antibody 49:56 cryoglobulin-like single-chain antibody 18:56 cryoglobulin-like single-chain antibody 18:56 Overexpression of cryoglobulin-like single-chain antibody induces morular cell phenotype via liquid-liquid phase separation in the secretory pathway organelles. 26036200 10 42 theme physicochemical 1872:1886 arg1 properties 1888:1897 intrinsic physicochemical properties 1862:1897 intrinsic physicochemical properties embedded in the overexpressed cargo protein 1862:1941 Morular cell phenotypes and cryoprecipitation were clearly underpinned by intrinsic physicochemical properties embedded in the overexpressed cargo protein. 26036200 0 43 theme antibody 49:56 arg1 Overexpression 0:13 Overexpression 0:13 Overexpression of cryoglobulin-like single-chain antibody 0:56 Overexpression of cryoglobulin-like single-chain antibody induces morular cell phenotype via liquid-liquid phase separation in the secretory pathway organelles. 26036200 5 44 theme droplet 1110:1116 arg1 formation 1118:1126 microscopic spherical protein droplet formation 1080:1126 microscopic spherical protein droplet formation 1080:1126 The turbidity of the culture media and the inclusion bodies that gave morular appearances were attributed to microscopic spherical protein droplet formation, a hallmark characteristic of liquid-liquid phase separation (LLPS) event. 26036200 5 44 theme droplet 1110:1116 arg1 hallmark 1131:1138 a hallmark 1129:1138 a hallmark characteristic of liquid-liquid phase separation (LLPS) event 1129:1200 The turbidity of the culture media and the inclusion bodies that gave morular appearances were attributed to microscopic spherical protein droplet formation, a hallmark characteristic of liquid-liquid phase separation (LLPS) event. 26036200 7 45 theme phenotype 1411:1419 arg1 propensity 1421:1430 morular phenotype propensity 1403:1430 morular phenotype propensity 1403:1430 Disruption of the N-linked glycosylation motif in the stp region enhanced morular phenotype propensity but reduced protein secretion. 26036200 4 46 theme model 593:597 arg1 protein 607:613 model scFv-Fc protein 593:613 model scFv-Fc protein 593:613 When model scFv-Fc protein was engineered to multimerize, by appending the secretory tailpiece (stp) of human immunoglobulin μ-chain to the C terminus, the resulting oligomeric scFv-Fc-stp protein acquired two unexpected properties: the induction of a morular cell phenotype during protein biosynthesis and the cryoprecipitation of secreted proteins in harvested cell culture media. 26036200 10 47 theme cargo 1929:1933 arg1 protein 1935:1941 the overexpressed cargo protein 1911:1941 the overexpressed cargo protein 1911:1941 Morular cell phenotypes and cryoprecipitation were clearly underpinned by intrinsic physicochemical properties embedded in the overexpressed cargo protein. 26036200 0 48 theme morular 66:72 arg1 phenotype 79:87 morular cell phenotype 66:87 morular cell phenotype 66:87 Overexpression of cryoglobulin-like single-chain antibody induces morular cell phenotype via liquid-liquid phase separation in the secretory pathway organelles. 26036200 4 49 theme phenotype 853:861 arg1 properties 809:818 two unexpected properties 794:818 two unexpected properties: the induction of a morular cell phenotype during protein biosynthesis and the cryoprecipitation of secreted proteins in harvested cell culture media 794:968 When model scFv-Fc protein was engineered to multimerize, by appending the secretory tailpiece (stp) of human immunoglobulin μ-chain to the C terminus, the resulting oligomeric scFv-Fc-stp protein acquired two unexpected properties: the induction of a morular cell phenotype during protein biosynthesis and the cryoprecipitation of secreted proteins in harvested cell culture media. 26036200 4 49 theme phenotype 853:861 arg1 induction 825:833 the induction 821:833 the induction of a morular cell phenotype during protein biosynthesis 821:889 When model scFv-Fc protein was engineered to multimerize, by appending the secretory tailpiece (stp) of human immunoglobulin μ-chain to the C terminus, the resulting oligomeric scFv-Fc-stp protein acquired two unexpected properties: the induction of a morular cell phenotype during protein biosynthesis and the cryoprecipitation of secreted proteins in harvested cell culture media. 26036200 4 49 theme phenotype 853:861 arg1 cryoprecipitation 899:915 the cryoprecipitation 895:915 the cryoprecipitation of secreted proteins in harvested cell culture media 895:968 When model scFv-Fc protein was engineered to multimerize, by appending the secretory tailpiece (stp) of human immunoglobulin μ-chain to the C terminus, the resulting oligomeric scFv-Fc-stp protein acquired two unexpected properties: the induction of a morular cell phenotype during protein biosynthesis and the cryoprecipitation of secreted proteins in harvested cell culture media. 26036200 1 50 theme plasma 277:282 arg1 dyscrasias 289:298 plasma cell dyscrasias 277:298 plasma cell dyscrasias 277:298 Cryoprecipitation of immunoglobulins is often reported in association with B-cell lymphoproliferative disorders and plasma cell dyscrasias. 26036200 7 51 theme stp 1383:1385 arg1 region 1387:1392 the stp region 1379:1392 the stp region 1379:1392 Disruption of the N-linked glycosylation motif in the stp region enhanced morular phenotype propensity but reduced protein secretion. 26036200 11 52 theme body 2106:2109 arg1 phenotype 2111:2119 morular Russell body phenotype 2090:2119 morular Russell body phenotype 2090:2119 Overproduction of condensation-prone secretory proteins that culminate in LLPS in the endoplasmic reticulum therefore serves as a path to produce morular Russell body phenotype. 26036200 10 53 theme intrinsic 1862:1870 arg1 properties 1888:1897 intrinsic physicochemical properties 1862:1897 intrinsic physicochemical properties embedded in the overexpressed cargo protein 1862:1941 Morular cell phenotypes and cryoprecipitation were clearly underpinned by intrinsic physicochemical properties embedded in the overexpressed cargo protein. 26036200 8 54 theme LLPS 1575:1578 arg1 induction 1562:1570 efficient induction 1552:1570 efficient induction of LLPS 1552:1578 Intermolecular disulfide bonds that stabilize Fc dimers and oligomers were necessary for efficient induction of LLPS, but their simultaneous elimination could not abrogate the LLPS propensity completely. 26036200 2 55 theme suitable 415:422 arg1 systems 437:443 suitable experimental systems 415:443 suitable experimental systems 415:443 However, the biochemical basis of such cryoglobulin behaviors is not well understood because of a general lack of suitable experimental systems. 26036200 9 56 theme LLPS 1772:1775 arg1 induction 1777:1785 LLPS induction 1772:1785 LLPS induction 1772:1785 Noncovalent protein-protein interactions between scFv-Fc-stp chains sufficiently established a basis for LLPS induction. 26036200 5 57 theme spherical 1092:1100 arg1 formation 1118:1126 microscopic spherical protein droplet formation 1080:1126 microscopic spherical protein droplet formation 1080:1126 The turbidity of the culture media and the inclusion bodies that gave morular appearances were attributed to microscopic spherical protein droplet formation, a hallmark characteristic of liquid-liquid phase separation (LLPS) event. 26036200 5 57 theme spherical 1092:1100 arg1 hallmark 1131:1138 a hallmark 1129:1138 a hallmark characteristic of liquid-liquid phase separation (LLPS) event 1129:1200 The turbidity of the culture media and the inclusion bodies that gave morular appearances were attributed to microscopic spherical protein droplet formation, a hallmark characteristic of liquid-liquid phase separation (LLPS) event. 26036200 10 58 from embedded 1899:1906 arg1 protein 1935:1941 the overexpressed cargo protein 1911:1941 the overexpressed cargo protein 1911:1941 Morular cell phenotypes and cryoprecipitation were clearly underpinned by intrinsic physicochemical properties embedded in the overexpressed cargo protein. 26036200 3 59 theme cryoglobulin-like 558:574 arg1 properties 576:585 cryoglobulin-like properties 558:585 cryoglobulin-like properties 558:585 Here, we report the identification and characterization of a single-chain antibody (scFv-Fc) that recapitulates cryoglobulin-like properties. 26036200 4 60 theme harvested 941:949 arg1 media 964:968 harvested cell culture media 941:968 harvested cell culture media 941:968 When model scFv-Fc protein was engineered to multimerize, by appending the secretory tailpiece (stp) of human immunoglobulin μ-chain to the C terminus, the resulting oligomeric scFv-Fc-stp protein acquired two unexpected properties: the induction of a morular cell phenotype during protein biosynthesis and the cryoprecipitation of secreted proteins in harvested cell culture media. 26036200 7 61 theme glycosylation 1356:1368 arg1 motif 1370:1374 the N-linked glycosylation motif 1343:1374 the N-linked glycosylation motif 1343:1374 Disruption of the N-linked glycosylation motif in the stp region enhanced morular phenotype propensity but reduced protein secretion. 26036200 2 62 theme cryoglobulin 340:351 arg1 behaviors 353:361 such cryoglobulin behaviors 335:361 such cryoglobulin behaviors 335:361 However, the biochemical basis of such cryoglobulin behaviors is not well understood because of a general lack of suitable experimental systems. 26036200 4 63 theme culture 956:962 arg1 media 964:968 harvested cell culture media 941:968 harvested cell culture media 941:968 When model scFv-Fc protein was engineered to multimerize, by appending the secretory tailpiece (stp) of human immunoglobulin μ-chain to the C terminus, the resulting oligomeric scFv-Fc-stp protein acquired two unexpected properties: the induction of a morular cell phenotype during protein biosynthesis and the cryoprecipitation of secreted proteins in harvested cell culture media. 26036200 6 64 theme covalent 1280:1287 arg1 oligomerization 1297:1311 covalent protein oligomerization 1280:1311 covalent protein oligomerization induced by stp 1280:1326 Mutagenesis approaches revealed that these two phenomena were independent of covalent protein oligomerization induced by stp. 26036200 11 65 theme morular 2090:2096 arg1 phenotype 2111:2119 morular Russell body phenotype 2090:2119 morular Russell body phenotype 2090:2119 Overproduction of condensation-prone secretory proteins that culminate in LLPS in the endoplasmic reticulum therefore serves as a path to produce morular Russell body phenotype. 26036200 10 66 theme Morular 1788:1794 arg1 phenotypes 1801:1810 Morular cell phenotypes 1788:1810 Morular cell phenotypes 1788:1810 Morular cell phenotypes and cryoprecipitation were clearly underpinned by intrinsic physicochemical properties embedded in the overexpressed cargo protein. 26036200 4 67 theme proteins 929:936 arg1 properties 809:818 two unexpected properties 794:818 two unexpected properties: the induction of a morular cell phenotype during protein biosynthesis and the cryoprecipitation of secreted proteins in harvested cell culture media 794:968 When model scFv-Fc protein was engineered to multimerize, by appending the secretory tailpiece (stp) of human immunoglobulin μ-chain to the C terminus, the resulting oligomeric scFv-Fc-stp protein acquired two unexpected properties: the induction of a morular cell phenotype during protein biosynthesis and the cryoprecipitation of secreted proteins in harvested cell culture media. 26036200 4 67 theme proteins 929:936 arg1 induction 825:833 the induction 821:833 the induction of a morular cell phenotype during protein biosynthesis 821:889 When model scFv-Fc protein was engineered to multimerize, by appending the secretory tailpiece (stp) of human immunoglobulin μ-chain to the C terminus, the resulting oligomeric scFv-Fc-stp protein acquired two unexpected properties: the induction of a morular cell phenotype during protein biosynthesis and the cryoprecipitation of secreted proteins in harvested cell culture media. 26036200 4 67 theme proteins 929:936 arg1 cryoprecipitation 899:915 the cryoprecipitation 895:915 the cryoprecipitation of secreted proteins in harvested cell culture media 895:968 When model scFv-Fc protein was engineered to multimerize, by appending the secretory tailpiece (stp) of human immunoglobulin μ-chain to the C terminus, the resulting oligomeric scFv-Fc-stp protein acquired two unexpected properties: the induction of a morular cell phenotype during protein biosynthesis and the cryoprecipitation of secreted proteins in harvested cell culture media. 26036200 4 68 theme C 728:728 arg1 terminus 730:737 the C terminus 724:737 the C terminus 724:737 When model scFv-Fc protein was engineered to multimerize, by appending the secretory tailpiece (stp) of human immunoglobulin μ-chain to the C terminus, the resulting oligomeric scFv-Fc-stp protein acquired two unexpected properties: the induction of a morular cell phenotype during protein biosynthesis and the cryoprecipitation of secreted proteins in harvested cell culture media. 26036200 1 69 theme B-cell 236:241 arg1 disorders 263:271 B-cell lymphoproliferative disorders 236:271 B-cell lymphoproliferative disorders 236:271 Cryoprecipitation of immunoglobulins is often reported in association with B-cell lymphoproliferative disorders and plasma cell dyscrasias. 26036200 11 70 theme Russell 2098:2104 arg1 phenotype 2111:2119 morular Russell body phenotype 2090:2119 morular Russell body phenotype 2090:2119 Overproduction of condensation-prone secretory proteins that culminate in LLPS in the endoplasmic reticulum therefore serves as a path to produce morular Russell body phenotype. 26036200 5 71 theme phase 1172:1176 arg1 LLPS 1190:1193 LLPS 1190:1193 LLPS 1190:1193 The turbidity of the culture media and the inclusion bodies that gave morular appearances were attributed to microscopic spherical protein droplet formation, a hallmark characteristic of liquid-liquid phase separation (LLPS) event. 26036200 5 71 theme phase 1172:1176 arg1 separation 1178:1187 liquid-liquid phase separation 1158:1187 liquid-liquid phase separation (LLPS) event 1158:1200 The turbidity of the culture media and the inclusion bodies that gave morular appearances were attributed to microscopic spherical protein droplet formation, a hallmark characteristic of liquid-liquid phase separation (LLPS) event. 26036200 8 72 theme simultaneous 1591:1602 arg1 elimination 1604:1614 their simultaneous elimination 1585:1614 their simultaneous elimination 1585:1614 Intermolecular disulfide bonds that stabilize Fc dimers and oligomers were necessary for efficient induction of LLPS, but their simultaneous elimination could not abrogate the LLPS propensity completely. 26036200 4 73 theme immunoglobulin 698:711 arg1 μ-chain 713:719 human immunoglobulin μ-chain 692:719 human immunoglobulin μ-chain 692:719 When model scFv-Fc protein was engineered to multimerize, by appending the secretory tailpiece (stp) of human immunoglobulin μ-chain to the C terminus, the resulting oligomeric scFv-Fc-stp protein acquired two unexpected properties: the induction of a morular cell phenotype during protein biosynthesis and the cryoprecipitation of secreted proteins in harvested cell culture media. 26036200 4 74 theme scFv-Fc-stp 765:775 arg1 protein 777:783 the resulting oligomeric scFv-Fc-stp protein 740:783 the resulting oligomeric scFv-Fc-stp protein 740:783 When model scFv-Fc protein was engineered to multimerize, by appending the secretory tailpiece (stp) of human immunoglobulin μ-chain to the C terminus, the resulting oligomeric scFv-Fc-stp protein acquired two unexpected properties: the induction of a morular cell phenotype during protein biosynthesis and the cryoprecipitation of secreted proteins in harvested cell culture media. 26036200 2 75 theme biochemical 314:324 arg1 basis 326:330 the biochemical basis 310:330 the biochemical basis of such cryoglobulin behaviors 310:361 However, the biochemical basis of such cryoglobulin behaviors is not well understood because of a general lack of suitable experimental systems. 26036200 5 76 theme media 1000:1004 arg1 turbidity 975:983 The turbidity 971:983 The turbidity of the culture media 971:1004 The turbidity of the culture media and the inclusion bodies that gave morular appearances were attributed to microscopic spherical protein droplet formation, a hallmark characteristic of liquid-liquid phase separation (LLPS) event. 26036200 5 76 theme media 1000:1004 arg1 bodies 1024:1029 the inclusion bodies 1010:1029 the inclusion bodies that gave morular appearances 1010:1059 The turbidity of the culture media and the inclusion bodies that gave morular appearances were attributed to microscopic spherical protein droplet formation, a hallmark characteristic of liquid-liquid phase separation (LLPS) event. 26036200 8 77 theme LLPS 1639:1642 arg1 propensity 1644:1653 the LLPS propensity 1635:1653 the LLPS propensity 1635:1653 Intermolecular disulfide bonds that stabilize Fc dimers and oligomers were necessary for efficient induction of LLPS, but their simultaneous elimination could not abrogate the LLPS propensity completely. 26036200 6 78 theme oligomerization 1297:1311 arg1 independent 1265:1275 independent 1265:1275 independent 1265:1275 Mutagenesis approaches revealed that these two phenomena were independent of covalent protein oligomerization induced by stp. 26036200 11 79 theme secretory 1981:1989 arg1 proteins 1991:1998 condensation-prone secretory proteins 1962:1998 condensation-prone secretory proteins that culminate in LLPS in the endoplasmic reticulum 1962:2050 Overproduction of condensation-prone secretory proteins that culminate in LLPS in the endoplasmic reticulum therefore serves as a path to produce morular Russell body phenotype. 26036200 0 80 theme phase 107:111 arg1 separation 113:122 liquid-liquid phase separation 93:122 liquid-liquid phase separation in the secretory pathway organelles 93:158 Overexpression of cryoglobulin-like single-chain antibody induces morular cell phenotype via liquid-liquid phase separation in the secretory pathway organelles. 26036200 9 81 theme protein-protein 1679:1693 arg1 interactions 1695:1706 Noncovalent protein-protein interactions 1667:1706 Noncovalent protein-protein interactions between scFv-Fc-stp chains 1667:1733 Noncovalent protein-protein interactions between scFv-Fc-stp chains sufficiently established a basis for LLPS induction. 26036200 4 82 theme resulting 744:752 arg1 protein 777:783 the resulting oligomeric scFv-Fc-stp protein 740:783 the resulting oligomeric scFv-Fc-stp protein 740:783 When model scFv-Fc protein was engineered to multimerize, by appending the secretory tailpiece (stp) of human immunoglobulin μ-chain to the C terminus, the resulting oligomeric scFv-Fc-stp protein acquired two unexpected properties: the induction of a morular cell phenotype during protein biosynthesis and the cryoprecipitation of secreted proteins in harvested cell culture media. 26036200 4 83 theme cell 848:851 arg1 phenotype 853:861 a morular cell phenotype 838:861 a morular cell phenotype 838:861 When model scFv-Fc protein was engineered to multimerize, by appending the secretory tailpiece (stp) of human immunoglobulin μ-chain to the C terminus, the resulting oligomeric scFv-Fc-stp protein acquired two unexpected properties: the induction of a morular cell phenotype during protein biosynthesis and the cryoprecipitation of secreted proteins in harvested cell culture media. 26036200 9 84 theme scFv-Fc-stp 1716:1726 arg1 chains 1728:1733 scFv-Fc-stp chains 1716:1733 scFv-Fc-stp chains 1716:1733 Noncovalent protein-protein interactions between scFv-Fc-stp chains sufficiently established a basis for LLPS induction. 26036200 8 85 theme Intermolecular 1463:1476 arg1 bonds 1488:1492 Intermolecular disulfide bonds 1463:1492 Intermolecular disulfide bonds that stabilize Fc dimers and oligomers 1463:1531 Intermolecular disulfide bonds that stabilize Fc dimers and oligomers were necessary for efficient induction of LLPS, but their simultaneous elimination could not abrogate the LLPS propensity completely. 26036200 6 86 theme Mutagenesis 1203:1213 arg1 approaches 1215:1224 Mutagenesis approaches 1203:1224 Mutagenesis approaches 1203:1224 Mutagenesis approaches revealed that these two phenomena were independent of covalent protein oligomerization induced by stp. 26036200 0 87 theme secretory 131:139 arg1 organelles 149:158 the secretory pathway organelles 127:158 the secretory pathway organelles 127:158 Overexpression of cryoglobulin-like single-chain antibody induces morular cell phenotype via liquid-liquid phase separation in the secretory pathway organelles. 26036200 4 88 from proteins 929:936 arg1 media 964:968 harvested cell culture media 941:968 harvested cell culture media 941:968 When model scFv-Fc protein was engineered to multimerize, by appending the secretory tailpiece (stp) of human immunoglobulin μ-chain to the C terminus, the resulting oligomeric scFv-Fc-stp protein acquired two unexpected properties: the induction of a morular cell phenotype during protein biosynthesis and the cryoprecipitation of secreted proteins in harvested cell culture media. 26036200 4 89 from induction 825:833 arg1 media 964:968 harvested cell culture media 941:968 harvested cell culture media 941:968 When model scFv-Fc protein was engineered to multimerize, by appending the secretory tailpiece (stp) of human immunoglobulin μ-chain to the C terminus, the resulting oligomeric scFv-Fc-stp protein acquired two unexpected properties: the induction of a morular cell phenotype during protein biosynthesis and the cryoprecipitation of secreted proteins in harvested cell culture media. 26036200 11 90 theme endoplasmic 2030:2040 arg1 reticulum 2042:2050 the endoplasmic reticulum 2026:2050 the endoplasmic reticulum 2026:2050 Overproduction of condensation-prone secretory proteins that culminate in LLPS in the endoplasmic reticulum therefore serves as a path to produce morular Russell body phenotype. 26036200 4 91 theme unexpected 798:807 arg1 properties 809:818 two unexpected properties 794:818 two unexpected properties: the induction of a morular cell phenotype during protein biosynthesis and the cryoprecipitation of secreted proteins in harvested cell culture media 794:968 When model scFv-Fc protein was engineered to multimerize, by appending the secretory tailpiece (stp) of human immunoglobulin μ-chain to the C terminus, the resulting oligomeric scFv-Fc-stp protein acquired two unexpected properties: the induction of a morular cell phenotype during protein biosynthesis and the cryoprecipitation of secreted proteins in harvested cell culture media. 26036200 4 91 theme unexpected 798:807 arg1 induction 825:833 the induction 821:833 the induction of a morular cell phenotype during protein biosynthesis 821:889 When model scFv-Fc protein was engineered to multimerize, by appending the secretory tailpiece (stp) of human immunoglobulin μ-chain to the C terminus, the resulting oligomeric scFv-Fc-stp protein acquired two unexpected properties: the induction of a morular cell phenotype during protein biosynthesis and the cryoprecipitation of secreted proteins in harvested cell culture media. 26036200 4 91 theme unexpected 798:807 arg1 cryoprecipitation 899:915 the cryoprecipitation 895:915 the cryoprecipitation of secreted proteins in harvested cell culture media 895:968 When model scFv-Fc protein was engineered to multimerize, by appending the secretory tailpiece (stp) of human immunoglobulin μ-chain to the C terminus, the resulting oligomeric scFv-Fc-stp protein acquired two unexpected properties: the induction of a morular cell phenotype during protein biosynthesis and the cryoprecipitation of secreted proteins in harvested cell culture media. 26036200 2 92 theme experimental 424:435 arg1 systems 437:443 suitable experimental systems 415:443 suitable experimental systems 415:443 However, the biochemical basis of such cryoglobulin behaviors is not well understood because of a general lack of suitable experimental systems. 26036200 0 93 theme single-chain 36:47 arg1 antibody 49:56 cryoglobulin-like single-chain antibody 18:56 cryoglobulin-like single-chain antibody 18:56 Overexpression of cryoglobulin-like single-chain antibody induces morular cell phenotype via liquid-liquid phase separation in the secretory pathway organelles. 26036200 4 94 theme protein 870:876 arg1 biosynthesis 878:889 protein biosynthesis 870:889 protein biosynthesis 870:889 When model scFv-Fc protein was engineered to multimerize, by appending the secretory tailpiece (stp) of human immunoglobulin μ-chain to the C terminus, the resulting oligomeric scFv-Fc-stp protein acquired two unexpected properties: the induction of a morular cell phenotype during protein biosynthesis and the cryoprecipitation of secreted proteins in harvested cell culture media. 26036200 7 95 gly glycosylation 1356:1368 arg2 motif 1370:1374 the N-linked glycosylation motif 1343:1374 the N-linked glycosylation motif 1343:1374 Disruption of the N-linked glycosylation motif in the stp region enhanced morular phenotype propensity but reduced protein secretion. 26036200 5 96 theme protein 1102:1108 arg1 formation 1118:1126 microscopic spherical protein droplet formation 1080:1126 microscopic spherical protein droplet formation 1080:1126 The turbidity of the culture media and the inclusion bodies that gave morular appearances were attributed to microscopic spherical protein droplet formation, a hallmark characteristic of liquid-liquid phase separation (LLPS) event. 26036200 5 96 theme protein 1102:1108 arg1 hallmark 1131:1138 a hallmark 1129:1138 a hallmark characteristic of liquid-liquid phase separation (LLPS) event 1129:1200 The turbidity of the culture media and the inclusion bodies that gave morular appearances were attributed to microscopic spherical protein droplet formation, a hallmark characteristic of liquid-liquid phase separation (LLPS) event. 26036200 7 97 theme morular 1403:1409 arg1 propensity 1421:1430 morular phenotype propensity 1403:1430 morular phenotype propensity 1403:1430 Disruption of the N-linked glycosylation motif in the stp region enhanced morular phenotype propensity but reduced protein secretion. 26036200 4 98 theme scFv-Fc 599:605 arg1 protein 607:613 model scFv-Fc protein 593:613 model scFv-Fc protein 593:613 When model scFv-Fc protein was engineered to multimerize, by appending the secretory tailpiece (stp) of human immunoglobulin μ-chain to the C terminus, the resulting oligomeric scFv-Fc-stp protein acquired two unexpected properties: the induction of a morular cell phenotype during protein biosynthesis and the cryoprecipitation of secreted proteins in harvested cell culture media. 26036200 3 99 theme single-chain 507:518 arg1 scFv-Fc 530:536 scFv-Fc 530:536 scFv-Fc 530:536 Here, we report the identification and characterization of a single-chain antibody (scFv-Fc) that recapitulates cryoglobulin-like properties. 26036200 3 99 theme single-chain 507:518 arg1 antibody 520:527 a single-chain antibody 505:527 a single-chain antibody (scFv-Fc) that recapitulates cryoglobulin-like properties 505:585 Here, we report the identification and characterization of a single-chain antibody (scFv-Fc) that recapitulates cryoglobulin-like properties. 26036200 0 100 theme cell 74:77 arg1 phenotype 79:87 morular cell phenotype 66:87 morular cell phenotype 66:87 Overexpression of cryoglobulin-like single-chain antibody induces morular cell phenotype via liquid-liquid phase separation in the secretory pathway organelles. 26036200 1 101 with association 219:229 arg1 dyscrasias 289:298 plasma cell dyscrasias 277:298 plasma cell dyscrasias 277:298 Cryoprecipitation of immunoglobulins is often reported in association with B-cell lymphoproliferative disorders and plasma cell dyscrasias. 26036200 1 101 with association 219:229 arg1 disorders 263:271 B-cell lymphoproliferative disorders 236:271 B-cell lymphoproliferative disorders 236:271 Cryoprecipitation of immunoglobulins is often reported in association with B-cell lymphoproliferative disorders and plasma cell dyscrasias. 26036200 10 102 theme overexpressed 1915:1927 arg1 protein 1935:1941 the overexpressed cargo protein 1911:1941 the overexpressed cargo protein 1911:1941 Morular cell phenotypes and cryoprecipitation were clearly underpinned by intrinsic physicochemical properties embedded in the overexpressed cargo protein. 26036200 5 103 dep separation 1178:1187 arg1 event 1196:1200 event 1196:1200 liquid-liquid phase separation (LLPS) event 1158:1200 The turbidity of the culture media and the inclusion bodies that gave morular appearances were attributed to microscopic spherical protein droplet formation, a hallmark characteristic of liquid-liquid phase separation (LLPS) event. 26036200 8 104 theme efficient 1552:1560 arg1 induction 1562:1570 efficient induction 1552:1570 efficient induction of LLPS 1552:1578 Intermolecular disulfide bonds that stabilize Fc dimers and oligomers were necessary for efficient induction of LLPS, but their simultaneous elimination could not abrogate the LLPS propensity completely. 26036200 1 105 theme cell 284:287 arg1 dyscrasias 289:298 plasma cell dyscrasias 277:298 plasma cell dyscrasias 277:298 Cryoprecipitation of immunoglobulins is often reported in association with B-cell lymphoproliferative disorders and plasma cell dyscrasias. 26036200 5 106 theme microscopic 1080:1090 arg1 formation 1118:1126 microscopic spherical protein droplet formation 1080:1126 microscopic spherical protein droplet formation 1080:1126 The turbidity of the culture media and the inclusion bodies that gave morular appearances were attributed to microscopic spherical protein droplet formation, a hallmark characteristic of liquid-liquid phase separation (LLPS) event. 26036200 5 106 theme microscopic 1080:1090 arg1 hallmark 1131:1138 a hallmark 1129:1138 a hallmark characteristic of liquid-liquid phase separation (LLPS) event 1129:1200 The turbidity of the culture media and the inclusion bodies that gave morular appearances were attributed to microscopic spherical protein droplet formation, a hallmark characteristic of liquid-liquid phase separation (LLPS) event. 26036200 7 107 theme motif 1370:1374 arg1 Disruption 1329:1338 Disruption 1329:1338 Disruption of the N-linked glycosylation motif in the stp region 1329:1392 Disruption of the N-linked glycosylation motif in the stp region enhanced morular phenotype propensity but reduced protein secretion. 26022515 2 0 theme GalNAc 452:457 arg1 antigen 421:427 the Forssman antigen 408:427 the Forssman antigen (N-acetylgalactosamine(GalNAc)α1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-ceramide) 408:499 SLL-2 binds with high affinity to the Forssman antigen (N-acetylgalactosamine(GalNAc)α1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-ceramide), and the presence of Forssman antigen-like sugar on the surface of Symbiodinium CS-156 cells was previously confirmed. 26022515 2 0 theme GalNAc 452:457 arg1 α1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-ceramide 459:498 N-acetylgalactosamine(GalNAc)α1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-ceramide 430:498 N-acetylgalactosamine(GalNAc)α1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-ceramide 430:498 SLL-2 binds with high affinity to the Forssman antigen (N-acetylgalactosamine(GalNAc)α1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-ceramide), and the presence of Forssman antigen-like sugar on the surface of Symbiodinium CS-156 cells was previously confirmed. 26022515 3 1 theme complex 682:688 arg1 structures 647:656 the crystal structures 635:656 the crystal structures of SLL-2 and its GalNAc complex as the first crystal structures of a lectin involved in the symbiosis between coral and dinoflagellate 635:791 Here we report the crystal structures of SLL-2 and its GalNAc complex as the first crystal structures of a lectin involved in the symbiosis between coral and dinoflagellate. 26022515 2 2 theme cells 588:592 arg1 surface 557:563 the surface 553:563 the surface of Symbiodinium CS-156 cells 553:592 SLL-2 binds with high affinity to the Forssman antigen (N-acetylgalactosamine(GalNAc)α1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-ceramide), and the presence of Forssman antigen-like sugar on the surface of Symbiodinium CS-156 cells was previously confirmed. 26022515 3 3 theme first 697:701 arg1 structures 711:720 the first crystal structures 693:720 the first crystal structures of a lectin involved in the symbiosis between coral and dinoflagellate 693:791 Here we report the crystal structures of SLL-2 and its GalNAc complex as the first crystal structures of a lectin involved in the symbiosis between coral and dinoflagellate. 26022515 0 4 from structure 8:16 arg1 octocoral 53:61 octocoral 53:61 octocoral 53:61 Crystal structure of a symbiosis-related lectin from octocoral. 26022515 4 5 theme binding 843:849 arg1 site 851:854 a galactose derivative binding site 820:854 a galactose derivative binding site common to H-type lectins 820:879 N-Linked sugar chains and a galactose derivative binding site common to H-type lectins were observed in each monomer of the hexameric SLL-2 crystal structure. 26022515 4 6 theme hexameric 918:926 arg1 structure 942:950 the hexameric SLL-2 crystal structure 914:950 the hexameric SLL-2 crystal structure 914:950 N-Linked sugar chains and a galactose derivative binding site common to H-type lectins were observed in each monomer of the hexameric SLL-2 crystal structure. 26022515 2 7 theme Symbiodinium 568:579 arg1 cells 588:592 Symbiodinium CS-156 cells 568:592 Symbiodinium CS-156 cells 568:592 SLL-2 binds with high affinity to the Forssman antigen (N-acetylgalactosamine(GalNAc)α1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-ceramide), and the presence of Forssman antigen-like sugar on the surface of Symbiodinium CS-156 cells was previously confirmed. 26022515 6 8 theme binding 1122:1128 arg1 mode 1130:1133 a possible binding mode 1111:1133 a possible binding mode between SLL-2 and Forssman antigen-like pentasaccharide 1111:1189 These structural features suggest a possible binding mode between SLL-2 and Forssman antigen-like pentasaccharide. 26022515 1 9 theme coral 252:256 arg1 dinoflagellate 230:243 an endosymbiotic dinoflagellate 213:243 an endosymbiotic dinoflagellate of the coral 213:256 D-Galactose-binding lectin from the octocoral, Sinularia lochmodes (SLL-2), distributes densely on the cell surface of microalgae, Symbiodinium sp., an endosymbiotic dinoflagellate of the coral, and is also shown to be a chemical cue that transforms dinoflagellate into a non-motile (coccoid) symbiotic state. 26022515 1 9 theme coral 252:256 arg1 microalgae 183:192 microalgae 183:192 microalgae 183:192 D-Galactose-binding lectin from the octocoral, Sinularia lochmodes (SLL-2), distributes densely on the cell surface of microalgae, Symbiodinium sp., an endosymbiotic dinoflagellate of the coral, and is also shown to be a chemical cue that transforms dinoflagellate into a non-motile (coccoid) symbiotic state. 26022515 0 10 from octocoral 53:61 arg1 lectin 41:46 a symbiosis-related lectin 21:46 a symbiosis-related lectin from octocoral 21:61 Crystal structure of a symbiosis-related lectin from octocoral. 26022515 0 10 from octocoral 53:61 arg1 structure 8:16 Crystal structure 0:16 Crystal structure of a symbiosis-related lectin from octocoral 0:61 Crystal structure of a symbiosis-related lectin from octocoral. 26022515 4 11 theme common 856:861 arg1 site 851:854 a galactose derivative binding site 820:854 a galactose derivative binding site common to H-type lectins 820:879 N-Linked sugar chains and a galactose derivative binding site common to H-type lectins were observed in each monomer of the hexameric SLL-2 crystal structure. 26022515 1 12 theme D-Galactose-binding 64:82 arg1 lectin 84:89 D-Galactose-binding lectin 64:89 D-Galactose-binding lectin from the octocoral 64:108 D-Galactose-binding lectin from the octocoral, Sinularia lochmodes (SLL-2), distributes densely on the cell surface of microalgae, Symbiodinium sp., an endosymbiotic dinoflagellate of the coral, and is also shown to be a chemical cue that transforms dinoflagellate into a non-motile (coccoid) symbiotic state. 26022515 1 12 theme D-Galactose-binding 64:82 arg1 lochmodes 121:129 Sinularia lochmodes 111:129 Sinularia lochmodes (SLL-2) 111:137 D-Galactose-binding lectin from the octocoral, Sinularia lochmodes (SLL-2), distributes densely on the cell surface of microalgae, Symbiodinium sp., an endosymbiotic dinoflagellate of the coral, and is also shown to be a chemical cue that transforms dinoflagellate into a non-motile (coccoid) symbiotic state. 26022515 1 12 theme D-Galactose-binding 64:82 arg1 cue 294:296 a chemical cue 283:296 a chemical cue that transforms dinoflagellate into a non-motile (coccoid) symbiotic state 283:371 D-Galactose-binding lectin from the octocoral, Sinularia lochmodes (SLL-2), distributes densely on the cell surface of microalgae, Symbiodinium sp., an endosymbiotic dinoflagellate of the coral, and is also shown to be a chemical cue that transforms dinoflagellate into a non-motile (coccoid) symbiotic state. 26022515 5 13 dep top 1028:1030 arg1 the 1024:1026 the 1024:1026 the 1024:1026 In addition, unique sugar-binding site-like regions were identified at the top and bottom of the hexameric SLL-2 structure. 26022515 4 14 theme crystal 934:940 arg1 structure 942:950 the hexameric SLL-2 crystal structure 914:950 the hexameric SLL-2 crystal structure 914:950 N-Linked sugar chains and a galactose derivative binding site common to H-type lectins were observed in each monomer of the hexameric SLL-2 crystal structure. 26022515 3 15 theme crystal 703:709 arg1 structures 711:720 the first crystal structures 693:720 the first crystal structures of a lectin involved in the symbiosis between coral and dinoflagellate 693:791 Here we report the crystal structures of SLL-2 and its GalNAc complex as the first crystal structures of a lectin involved in the symbiosis between coral and dinoflagellate. 26022515 6 16 theme Forssman 1153:1160 arg1 pentasaccharide 1175:1189 Forssman antigen-like pentasaccharide 1153:1189 Forssman antigen-like pentasaccharide 1153:1189 These structural features suggest a possible binding mode between SLL-2 and Forssman antigen-like pentasaccharide. 26022515 4 17 theme SLL-2 928:932 arg1 structure 942:950 the hexameric SLL-2 crystal structure 914:950 the hexameric SLL-2 crystal structure 914:950 N-Linked sugar chains and a galactose derivative binding site common to H-type lectins were observed in each monomer of the hexameric SLL-2 crystal structure. 26022515 1 18 theme non-motile 336:345 arg1 state 367:371 a non-motile (coccoid) symbiotic state 334:371 a non-motile (coccoid) symbiotic state 334:371 D-Galactose-binding lectin from the octocoral, Sinularia lochmodes (SLL-2), distributes densely on the cell surface of microalgae, Symbiodinium sp., an endosymbiotic dinoflagellate of the coral, and is also shown to be a chemical cue that transforms dinoflagellate into a non-motile (coccoid) symbiotic state. 26022515 0 19 theme lectin 41:46 arg1 structure 8:16 Crystal structure 0:16 Crystal structure of a symbiosis-related lectin from octocoral 0:61 Crystal structure of a symbiosis-related lectin from octocoral. 26022515 1 20 theme cell 167:170 arg1 surface 172:178 the cell surface 163:178 the cell surface of microalgae, Symbiodinium sp., an endosymbiotic dinoflagellate of the coral, 163:257 D-Galactose-binding lectin from the octocoral, Sinularia lochmodes (SLL-2), distributes densely on the cell surface of microalgae, Symbiodinium sp., an endosymbiotic dinoflagellate of the coral, and is also shown to be a chemical cue that transforms dinoflagellate into a non-motile (coccoid) symbiotic state. 26022515 4 21 theme derivative 832:841 arg1 site 851:854 a galactose derivative binding site 820:854 a galactose derivative binding site common to H-type lectins 820:879 N-Linked sugar chains and a galactose derivative binding site common to H-type lectins were observed in each monomer of the hexameric SLL-2 crystal structure. 26022515 0 22 theme Crystal 0:6 arg1 structure 8:16 Crystal structure 0:16 Crystal structure of a symbiosis-related lectin from octocoral 0:61 Crystal structure of a symbiosis-related lectin from octocoral. 26022515 4 23 theme galactose 822:830 arg1 site 851:854 a galactose derivative binding site 820:854 a galactose derivative binding site common to H-type lectins 820:879 N-Linked sugar chains and a galactose derivative binding site common to H-type lectins were observed in each monomer of the hexameric SLL-2 crystal structure. 26022515 3 24 theme lectin 727:732 arg1 structures 711:720 the first crystal structures 693:720 the first crystal structures of a lectin involved in the symbiosis between coral and dinoflagellate 693:791 Here we report the crystal structures of SLL-2 and its GalNAc complex as the first crystal structures of a lectin involved in the symbiosis between coral and dinoflagellate. 26022515 2 25 theme antigen-like 531:542 arg1 sugar 544:548 Forssman antigen-like sugar 522:548 Forssman antigen-like sugar 522:548 SLL-2 binds with high affinity to the Forssman antigen (N-acetylgalactosamine(GalNAc)α1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-ceramide), and the presence of Forssman antigen-like sugar on the surface of Symbiodinium CS-156 cells was previously confirmed. 26022515 1 26 theme microalgae 183:192 arg1 surface 172:178 the cell surface 163:178 the cell surface of microalgae, Symbiodinium sp., an endosymbiotic dinoflagellate of the coral, 163:257 D-Galactose-binding lectin from the octocoral, Sinularia lochmodes (SLL-2), distributes densely on the cell surface of microalgae, Symbiodinium sp., an endosymbiotic dinoflagellate of the coral, and is also shown to be a chemical cue that transforms dinoflagellate into a non-motile (coccoid) symbiotic state. 26022515 2 27 theme high 391:394 arg1 affinity 396:403 high affinity 391:403 high affinity 391:403 SLL-2 binds with high affinity to the Forssman antigen (N-acetylgalactosamine(GalNAc)α1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-ceramide), and the presence of Forssman antigen-like sugar on the surface of Symbiodinium CS-156 cells was previously confirmed. 26022515 2 28 theme Forssman 522:529 arg1 sugar 544:548 Forssman antigen-like sugar 522:548 Forssman antigen-like sugar 522:548 SLL-2 binds with high affinity to the Forssman antigen (N-acetylgalactosamine(GalNAc)α1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-ceramide), and the presence of Forssman antigen-like sugar on the surface of Symbiodinium CS-156 cells was previously confirmed. 26022515 1 29 theme coccoid 348:354 arg1 state 367:371 a non-motile (coccoid) symbiotic state 334:371 a non-motile (coccoid) symbiotic state 334:371 D-Galactose-binding lectin from the octocoral, Sinularia lochmodes (SLL-2), distributes densely on the cell surface of microalgae, Symbiodinium sp., an endosymbiotic dinoflagellate of the coral, and is also shown to be a chemical cue that transforms dinoflagellate into a non-motile (coccoid) symbiotic state. 26022515 1 30 theme Sinularia 111:119 arg1 SLL-2 132:136 SLL-2 132:136 SLL-2 132:136 D-Galactose-binding lectin from the octocoral, Sinularia lochmodes (SLL-2), distributes densely on the cell surface of microalgae, Symbiodinium sp., an endosymbiotic dinoflagellate of the coral, and is also shown to be a chemical cue that transforms dinoflagellate into a non-motile (coccoid) symbiotic state. 26022515 1 30 theme Sinularia 111:119 arg1 lectin 84:89 D-Galactose-binding lectin 64:89 D-Galactose-binding lectin from the octocoral 64:108 D-Galactose-binding lectin from the octocoral, Sinularia lochmodes (SLL-2), distributes densely on the cell surface of microalgae, Symbiodinium sp., an endosymbiotic dinoflagellate of the coral, and is also shown to be a chemical cue that transforms dinoflagellate into a non-motile (coccoid) symbiotic state. 26022515 1 30 theme Sinularia 111:119 arg1 lochmodes 121:129 Sinularia lochmodes 111:129 Sinularia lochmodes (SLL-2) 111:137 D-Galactose-binding lectin from the octocoral, Sinularia lochmodes (SLL-2), distributes densely on the cell surface of microalgae, Symbiodinium sp., an endosymbiotic dinoflagellate of the coral, and is also shown to be a chemical cue that transforms dinoflagellate into a non-motile (coccoid) symbiotic state. 26022515 2 31 attach presence 510:517 arg2 sugar 544:548 Forssman antigen-like sugar 522:548 Forssman antigen-like sugar 522:548 SLL-2 binds with high affinity to the Forssman antigen (N-acetylgalactosamine(GalNAc)α1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-ceramide), and the presence of Forssman antigen-like sugar on the surface of Symbiodinium CS-156 cells was previously confirmed. 26022515 2 31 attach presence 510:517 arg1 surface 557:563 the surface 553:563 the surface of Symbiodinium CS-156 cells 553:592 SLL-2 binds with high affinity to the Forssman antigen (N-acetylgalactosamine(GalNAc)α1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-ceramide), and the presence of Forssman antigen-like sugar on the surface of Symbiodinium CS-156 cells was previously confirmed. 26022515 2 32 theme N-acetylgalactosamine 430:450 arg1 antigen 421:427 the Forssman antigen 408:427 the Forssman antigen (N-acetylgalactosamine(GalNAc)α1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-ceramide) 408:499 SLL-2 binds with high affinity to the Forssman antigen (N-acetylgalactosamine(GalNAc)α1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-ceramide), and the presence of Forssman antigen-like sugar on the surface of Symbiodinium CS-156 cells was previously confirmed. 26022515 2 32 theme N-acetylgalactosamine 430:450 arg1 α1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-ceramide 459:498 N-acetylgalactosamine(GalNAc)α1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-ceramide 430:498 N-acetylgalactosamine(GalNAc)α1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-ceramide 430:498 SLL-2 binds with high affinity to the Forssman antigen (N-acetylgalactosamine(GalNAc)α1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-ceramide), and the presence of Forssman antigen-like sugar on the surface of Symbiodinium CS-156 cells was previously confirmed. 26022515 4 33 theme N-Linked 794:801 arg1 chains 809:814 N-Linked sugar chains 794:814 N-Linked sugar chains 794:814 N-Linked sugar chains and a galactose derivative binding site common to H-type lectins were observed in each monomer of the hexameric SLL-2 crystal structure. 26022515 4 34 located observed 886:893 arg2 chains 809:814 N-Linked sugar chains 794:814 N-Linked sugar chains 794:814 N-Linked sugar chains and a galactose derivative binding site common to H-type lectins were observed in each monomer of the hexameric SLL-2 crystal structure. 26022515 4 34 located observed 886:893 arg2 site 851:854 a galactose derivative binding site 820:854 a galactose derivative binding site common to H-type lectins 820:879 N-Linked sugar chains and a galactose derivative binding site common to H-type lectins were observed in each monomer of the hexameric SLL-2 crystal structure. 26022515 4 34 located observed 886:893 arg1 monomer 903:909 each monomer 898:909 each monomer of the hexameric SLL-2 crystal structure 898:950 N-Linked sugar chains and a galactose derivative binding site common to H-type lectins were observed in each monomer of the hexameric SLL-2 crystal structure. 26022515 4 34 located observed 886:893 arg1 structure 942:950 the hexameric SLL-2 crystal structure 914:950 the hexameric SLL-2 crystal structure 914:950 N-Linked sugar chains and a galactose derivative binding site common to H-type lectins were observed in each monomer of the hexameric SLL-2 crystal structure. 26022515 1 35 theme Symbiodinium 195:206 arg1 microalgae 183:192 microalgae 183:192 microalgae 183:192 D-Galactose-binding lectin from the octocoral, Sinularia lochmodes (SLL-2), distributes densely on the cell surface of microalgae, Symbiodinium sp., an endosymbiotic dinoflagellate of the coral, and is also shown to be a chemical cue that transforms dinoflagellate into a non-motile (coccoid) symbiotic state. 26022515 1 35 theme Symbiodinium 195:206 arg1 sp. 208:210 Symbiodinium sp. 195:210 Symbiodinium sp. 195:210 D-Galactose-binding lectin from the octocoral, Sinularia lochmodes (SLL-2), distributes densely on the cell surface of microalgae, Symbiodinium sp., an endosymbiotic dinoflagellate of the coral, and is also shown to be a chemical cue that transforms dinoflagellate into a non-motile (coccoid) symbiotic state. 26022515 0 36 theme symbiosis-related 23:39 arg1 lectin 41:46 a symbiosis-related lectin 21:46 a symbiosis-related lectin from octocoral 21:61 Crystal structure of a symbiosis-related lectin from octocoral. 26022515 1 37 theme symbiotic 357:365 arg1 state 367:371 a non-motile (coccoid) symbiotic state 334:371 a non-motile (coccoid) symbiotic state 334:371 D-Galactose-binding lectin from the octocoral, Sinularia lochmodes (SLL-2), distributes densely on the cell surface of microalgae, Symbiodinium sp., an endosymbiotic dinoflagellate of the coral, and is also shown to be a chemical cue that transforms dinoflagellate into a non-motile (coccoid) symbiotic state. 26022515 5 38 theme structure 1066:1074 arg1 bottom 1036:1041 bottom 1036:1041 bottom 1036:1041 In addition, unique sugar-binding site-like regions were identified at the top and bottom of the hexameric SLL-2 structure. 26022515 5 38 theme structure 1066:1074 arg1 top 1028:1030 top 1028:1030 top 1028:1030 In addition, unique sugar-binding site-like regions were identified at the top and bottom of the hexameric SLL-2 structure. 26022515 5 39 theme SLL-2 1060:1064 arg1 structure 1066:1074 the hexameric SLL-2 structure 1046:1074 the hexameric SLL-2 structure 1046:1074 In addition, unique sugar-binding site-like regions were identified at the top and bottom of the hexameric SLL-2 structure. 26022515 6 40 theme possible 1113:1120 arg1 mode 1130:1133 a possible binding mode 1111:1133 a possible binding mode between SLL-2 and Forssman antigen-like pentasaccharide 1111:1189 These structural features suggest a possible binding mode between SLL-2 and Forssman antigen-like pentasaccharide. 26022515 2 41 theme Forssman 412:419 arg1 antigen 421:427 the Forssman antigen 408:427 the Forssman antigen (N-acetylgalactosamine(GalNAc)α1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-ceramide) 408:499 SLL-2 binds with high affinity to the Forssman antigen (N-acetylgalactosamine(GalNAc)α1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-ceramide), and the presence of Forssman antigen-like sugar on the surface of Symbiodinium CS-156 cells was previously confirmed. 26022515 2 41 theme Forssman 412:419 arg1 α1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-ceramide 459:498 N-acetylgalactosamine(GalNAc)α1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-ceramide 430:498 N-acetylgalactosamine(GalNAc)α1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-ceramide 430:498 SLL-2 binds with high affinity to the Forssman antigen (N-acetylgalactosamine(GalNAc)α1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-ceramide), and the presence of Forssman antigen-like sugar on the surface of Symbiodinium CS-156 cells was previously confirmed. 26022515 6 42 theme antigen-like 1162:1173 arg1 pentasaccharide 1175:1189 Forssman antigen-like pentasaccharide 1153:1189 Forssman antigen-like pentasaccharide 1153:1189 These structural features suggest a possible binding mode between SLL-2 and Forssman antigen-like pentasaccharide. 26022515 4 43 theme H-type 866:871 arg1 lectins 873:879 H-type lectins 866:879 H-type lectins 866:879 N-Linked sugar chains and a galactose derivative binding site common to H-type lectins were observed in each monomer of the hexameric SLL-2 crystal structure. 26022515 4 44 theme sugar 803:807 arg1 chains 809:814 N-Linked sugar chains 794:814 N-Linked sugar chains 794:814 N-Linked sugar chains and a galactose derivative binding site common to H-type lectins were observed in each monomer of the hexameric SLL-2 crystal structure. 26022515 5 45 theme hexameric 1050:1058 arg1 structure 1066:1074 the hexameric SLL-2 structure 1046:1074 the hexameric SLL-2 structure 1046:1074 In addition, unique sugar-binding site-like regions were identified at the top and bottom of the hexameric SLL-2 structure. 26022515 1 46 theme chemical 285:292 arg1 lectin 84:89 D-Galactose-binding lectin 64:89 D-Galactose-binding lectin from the octocoral 64:108 D-Galactose-binding lectin from the octocoral, Sinularia lochmodes (SLL-2), distributes densely on the cell surface of microalgae, Symbiodinium sp., an endosymbiotic dinoflagellate of the coral, and is also shown to be a chemical cue that transforms dinoflagellate into a non-motile (coccoid) symbiotic state. 26022515 1 46 theme chemical 285:292 arg1 cue 294:296 a chemical cue 283:296 a chemical cue that transforms dinoflagellate into a non-motile (coccoid) symbiotic state 283:371 D-Galactose-binding lectin from the octocoral, Sinularia lochmodes (SLL-2), distributes densely on the cell surface of microalgae, Symbiodinium sp., an endosymbiotic dinoflagellate of the coral, and is also shown to be a chemical cue that transforms dinoflagellate into a non-motile (coccoid) symbiotic state. 26022515 3 47 theme SLL-2 661:665 arg1 structures 647:656 the crystal structures 635:656 the crystal structures of SLL-2 and its GalNAc complex as the first crystal structures of a lectin involved in the symbiosis between coral and dinoflagellate 635:791 Here we report the crystal structures of SLL-2 and its GalNAc complex as the first crystal structures of a lectin involved in the symbiosis between coral and dinoflagellate. 26022515 2 48 theme sugar 544:548 arg1 presence 510:517 the presence 506:517 the presence of Forssman antigen-like sugar on the surface of Symbiodinium CS-156 cells 506:592 SLL-2 binds with high affinity to the Forssman antigen (N-acetylgalactosamine(GalNAc)α1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-ceramide), and the presence of Forssman antigen-like sugar on the surface of Symbiodinium CS-156 cells was previously confirmed. 26022515 3 49 theme crystal 639:645 arg1 structures 647:656 the crystal structures 635:656 the crystal structures of SLL-2 and its GalNAc complex as the first crystal structures of a lectin involved in the symbiosis between coral and dinoflagellate 635:791 Here we report the crystal structures of SLL-2 and its GalNAc complex as the first crystal structures of a lectin involved in the symbiosis between coral and dinoflagellate. 26022515 5 50 theme unique 966:971 arg1 regions 997:1003 unique sugar-binding site-like regions 966:1003 unique sugar-binding site-like regions 966:1003 In addition, unique sugar-binding site-like regions were identified at the top and bottom of the hexameric SLL-2 structure. 26022515 2 51 from presence 510:517 arg1 surface 557:563 the surface 553:563 the surface of Symbiodinium CS-156 cells 553:592 SLL-2 binds with high affinity to the Forssman antigen (N-acetylgalactosamine(GalNAc)α1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-ceramide), and the presence of Forssman antigen-like sugar on the surface of Symbiodinium CS-156 cells was previously confirmed. 26022515 5 52 theme sugar-binding 973:985 arg1 regions 997:1003 unique sugar-binding site-like regions 966:1003 unique sugar-binding site-like regions 966:1003 In addition, unique sugar-binding site-like regions were identified at the top and bottom of the hexameric SLL-2 structure. 26022515 6 53 theme structural 1083:1092 arg1 features 1094:1101 These structural features 1077:1101 These structural features 1077:1101 These structural features suggest a possible binding mode between SLL-2 and Forssman antigen-like pentasaccharide. 26022515 1 54 from octocoral 100:108 arg1 lectin 84:89 D-Galactose-binding lectin 64:89 D-Galactose-binding lectin from the octocoral 64:108 D-Galactose-binding lectin from the octocoral, Sinularia lochmodes (SLL-2), distributes densely on the cell surface of microalgae, Symbiodinium sp., an endosymbiotic dinoflagellate of the coral, and is also shown to be a chemical cue that transforms dinoflagellate into a non-motile (coccoid) symbiotic state. 26022515 1 54 from octocoral 100:108 arg1 lochmodes 121:129 Sinularia lochmodes 111:129 Sinularia lochmodes (SLL-2) 111:137 D-Galactose-binding lectin from the octocoral, Sinularia lochmodes (SLL-2), distributes densely on the cell surface of microalgae, Symbiodinium sp., an endosymbiotic dinoflagellate of the coral, and is also shown to be a chemical cue that transforms dinoflagellate into a non-motile (coccoid) symbiotic state. 26022515 1 54 from octocoral 100:108 arg1 cue 294:296 a chemical cue 283:296 a chemical cue that transforms dinoflagellate into a non-motile (coccoid) symbiotic state 283:371 D-Galactose-binding lectin from the octocoral, Sinularia lochmodes (SLL-2), distributes densely on the cell surface of microalgae, Symbiodinium sp., an endosymbiotic dinoflagellate of the coral, and is also shown to be a chemical cue that transforms dinoflagellate into a non-motile (coccoid) symbiotic state. 26022515 1 55 theme endosymbiotic 216:228 arg1 dinoflagellate 230:243 an endosymbiotic dinoflagellate 213:243 an endosymbiotic dinoflagellate of the coral 213:256 D-Galactose-binding lectin from the octocoral, Sinularia lochmodes (SLL-2), distributes densely on the cell surface of microalgae, Symbiodinium sp., an endosymbiotic dinoflagellate of the coral, and is also shown to be a chemical cue that transforms dinoflagellate into a non-motile (coccoid) symbiotic state. 26022515 1 55 theme endosymbiotic 216:228 arg1 microalgae 183:192 microalgae 183:192 microalgae 183:192 D-Galactose-binding lectin from the octocoral, Sinularia lochmodes (SLL-2), distributes densely on the cell surface of microalgae, Symbiodinium sp., an endosymbiotic dinoflagellate of the coral, and is also shown to be a chemical cue that transforms dinoflagellate into a non-motile (coccoid) symbiotic state. 26022515 4 56 theme structure 942:950 arg1 monomer 903:909 each monomer 898:909 each monomer of the hexameric SLL-2 crystal structure 898:950 N-Linked sugar chains and a galactose derivative binding site common to H-type lectins were observed in each monomer of the hexameric SLL-2 crystal structure. 26022515 4 56 theme structure 942:950 arg1 structure 942:950 the hexameric SLL-2 crystal structure 914:950 the hexameric SLL-2 crystal structure 914:950 N-Linked sugar chains and a galactose derivative binding site common to H-type lectins were observed in each monomer of the hexameric SLL-2 crystal structure. 26022515 3 57 theme GalNAc 675:680 arg1 complex 682:688 its GalNAc complex 671:688 its GalNAc complex 671:688 Here we report the crystal structures of SLL-2 and its GalNAc complex as the first crystal structures of a lectin involved in the symbiosis between coral and dinoflagellate. 26022515 5 58 theme site-like 987:995 arg1 regions 997:1003 unique sugar-binding site-like regions 966:1003 unique sugar-binding site-like regions 966:1003 In addition, unique sugar-binding site-like regions were identified at the top and bottom of the hexameric SLL-2 structure. 28072827 4 0 theme sialic 1042:1047 arg1 acid 1049:1052 the sialic acid 1038:1052 the sialic acid 1038:1052 To overcome this issue, mild alkali treatment was used to hydrolyze lactone of the sialic acid to their neutral formation, which had no impact on the analysis of other glycans before and after the treatment. 28072827 5 1 theme alkali 1189:1194 arg1 helpful 1215:1221 helpful 1215:1221 helpful 1215:1221 As a result, the mild alkali treatment might be helpful to obtain quantitative glycan profiling of the mAbs drugs with enhanced accuracy and robustness. 28072827 5 1 theme alkali 1189:1194 arg1 treatment 1196:1204 the mild alkali treatment 1180:1204 the mild alkali treatment 1180:1204 As a result, the mild alkali treatment might be helpful to obtain quantitative glycan profiling of the mAbs drugs with enhanced accuracy and robustness. 28072827 5 2 with drugs 1275:1279 arg1 robustness 1308:1317 robustness 1308:1317 robustness 1308:1317 As a result, the mild alkali treatment might be helpful to obtain quantitative glycan profiling of the mAbs drugs with enhanced accuracy and robustness. 28072827 5 2 with drugs 1275:1279 arg1 accuracy 1295:1302 enhanced accuracy 1286:1302 enhanced accuracy 1286:1302 As a result, the mild alkali treatment might be helpful to obtain quantitative glycan profiling of the mAbs drugs with enhanced accuracy and robustness. 28072827 3 3 located observed 702:709 arg2 presence 612:619 The presence 608:619 The presence of minor N-linked glycans containing sialic acid lactone residues (NeuAcLac) 608:696 The presence of minor N-linked glycans containing sialic acid lactone residues (NeuAcLac) was observed in the biosimilar for the first time, which could influence the quantitative analysis of sialylated glycans and interfere with quantification of neutral glycans when it was analyzed by high performance liquid chromatography fluorescence (HPLC-FL). 28072827 3 3 located observed 702:709 arg1 biosimilar 718:727 the biosimilar 714:727 the biosimilar 714:727 The presence of minor N-linked glycans containing sialic acid lactone residues (NeuAcLac) was observed in the biosimilar for the first time, which could influence the quantitative analysis of sialylated glycans and interfere with quantification of neutral glycans when it was analyzed by high performance liquid chromatography fluorescence (HPLC-FL). 28072827 3 4 theme chromatography 920:933 arg1 fluorescence 935:946 high performance liquid chromatography fluorescence 896:946 high performance liquid chromatography fluorescence (HPLC-FL) 896:956 The presence of minor N-linked glycans containing sialic acid lactone residues (NeuAcLac) was observed in the biosimilar for the first time, which could influence the quantitative analysis of sialylated glycans and interfere with quantification of neutral glycans when it was analyzed by high performance liquid chromatography fluorescence (HPLC-FL). 28072827 3 4 theme chromatography 920:933 arg1 HPLC-FL 949:955 HPLC-FL 949:955 HPLC-FL 949:955 The presence of minor N-linked glycans containing sialic acid lactone residues (NeuAcLac) was observed in the biosimilar for the first time, which could influence the quantitative analysis of sialylated glycans and interfere with quantification of neutral glycans when it was analyzed by high performance liquid chromatography fluorescence (HPLC-FL). 28072827 1 5 gly glycosylation 103:115 arg1 mAbs 124:127 the mAbs 120:127 the mAbs 120:127 Monitoring glycosylation of the mAbs have been emphasized and routinely characterized in biopharmaceutical industries because the carbohydrate components are closely related to the safety, efficacy, and consistency of the antibodies. 28072827 1 5 gly glycosylation 103:115 arg1 industries 199:208 biopharmaceutical industries 181:208 biopharmaceutical industries 181:208 Monitoring glycosylation of the mAbs have been emphasized and routinely characterized in biopharmaceutical industries because the carbohydrate components are closely related to the safety, efficacy, and consistency of the antibodies. 28072827 3 6 theme first 737:741 arg1 time 743:746 the first time 733:746 the first time 733:746 The presence of minor N-linked glycans containing sialic acid lactone residues (NeuAcLac) was observed in the biosimilar for the first time, which could influence the quantitative analysis of sialylated glycans and interfere with quantification of neutral glycans when it was analyzed by high performance liquid chromatography fluorescence (HPLC-FL). 28072827 2 7 with combination 517:527 arg1 MALDI-MS 597:604 MALDI-MS 597:604 MALDI-MS 597:604 In this study, the comprehensive glycan profiling of a biosimilar candidate of cetuximab was successfully characterized using Normal phase high-performance liquid chromatography (NP-HPLC) in combination with Matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS). 28072827 2 7 with combination 517:527 arg1 spectrometry 583:594 Matrix assisted laser desorption/ionization mass spectrometry 534:594 Matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS) 534:605 In this study, the comprehensive glycan profiling of a biosimilar candidate of cetuximab was successfully characterized using Normal phase high-performance liquid chromatography (NP-HPLC) in combination with Matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS). 28072827 5 8 theme drugs 1275:1279 arg1 profiling 1253:1261 quantitative glycan profiling 1233:1261 quantitative glycan profiling of the mAbs drugs with enhanced accuracy and robustness 1233:1317 As a result, the mild alkali treatment might be helpful to obtain quantitative glycan profiling of the mAbs drugs with enhanced accuracy and robustness. 28072827 2 9 theme mass 578:581 arg1 MALDI-MS 597:604 MALDI-MS 597:604 MALDI-MS 597:604 In this study, the comprehensive glycan profiling of a biosimilar candidate of cetuximab was successfully characterized using Normal phase high-performance liquid chromatography (NP-HPLC) in combination with Matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS). 28072827 2 9 theme mass 578:581 arg1 spectrometry 583:594 Matrix assisted laser desorption/ionization mass spectrometry 534:594 Matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS) 534:605 In this study, the comprehensive glycan profiling of a biosimilar candidate of cetuximab was successfully characterized using Normal phase high-performance liquid chromatography (NP-HPLC) in combination with Matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS). 28072827 3 10 gly sialylated 800:809 arg1 glycans 811:817 sialylated glycans 800:817 sialylated glycans 800:817 The presence of minor N-linked glycans containing sialic acid lactone residues (NeuAcLac) was observed in the biosimilar for the first time, which could influence the quantitative analysis of sialylated glycans and interfere with quantification of neutral glycans when it was analyzed by high performance liquid chromatography fluorescence (HPLC-FL). 28072827 4 11 contain had 1088:1090 arg2 impact 1095:1100 no impact 1092:1100 no impact on the analysis of other glycans 1092:1133 To overcome this issue, mild alkali treatment was used to hydrolyze lactone of the sialic acid to their neutral formation, which had no impact on the analysis of other glycans before and after the treatment. 28072827 4 11 contain had 1088:1090 arg1 formation 1071:1079 their neutral formation 1057:1079 their neutral formation 1057:1079 To overcome this issue, mild alkali treatment was used to hydrolyze lactone of the sialic acid to their neutral formation, which had no impact on the analysis of other glycans before and after the treatment. 28072827 3 12 contain containing 647:656 arg2 NeuAcLac 688:695 NeuAcLac 688:695 NeuAcLac 688:695 The presence of minor N-linked glycans containing sialic acid lactone residues (NeuAcLac) was observed in the biosimilar for the first time, which could influence the quantitative analysis of sialylated glycans and interfere with quantification of neutral glycans when it was analyzed by high performance liquid chromatography fluorescence (HPLC-FL). 28072827 3 12 contain containing 647:656 arg2 residues 678:685 sialic acid lactone residues 658:685 sialic acid lactone residues (NeuAcLac) 658:696 The presence of minor N-linked glycans containing sialic acid lactone residues (NeuAcLac) was observed in the biosimilar for the first time, which could influence the quantitative analysis of sialylated glycans and interfere with quantification of neutral glycans when it was analyzed by high performance liquid chromatography fluorescence (HPLC-FL). 28072827 3 12 contain containing 647:656 arg1 glycans 639:645 minor N-linked glycans 624:645 minor N-linked glycans containing sialic acid lactone residues (NeuAcLac) 624:696 The presence of minor N-linked glycans containing sialic acid lactone residues (NeuAcLac) was observed in the biosimilar for the first time, which could influence the quantitative analysis of sialylated glycans and interfere with quantification of neutral glycans when it was analyzed by high performance liquid chromatography fluorescence (HPLC-FL). 28072827 2 13 theme desorption/ionization 556:576 arg1 MALDI-MS 597:604 MALDI-MS 597:604 MALDI-MS 597:604 In this study, the comprehensive glycan profiling of a biosimilar candidate of cetuximab was successfully characterized using Normal phase high-performance liquid chromatography (NP-HPLC) in combination with Matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS). 28072827 2 13 theme desorption/ionization 556:576 arg1 spectrometry 583:594 Matrix assisted laser desorption/ionization mass spectrometry 534:594 Matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS) 534:605 In this study, the comprehensive glycan profiling of a biosimilar candidate of cetuximab was successfully characterized using Normal phase high-performance liquid chromatography (NP-HPLC) in combination with Matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS). 28072827 2 14 theme glycan 359:364 arg1 profiling 366:374 the comprehensive glycan profiling 341:374 the comprehensive glycan profiling of a biosimilar candidate of cetuximab 341:413 In this study, the comprehensive glycan profiling of a biosimilar candidate of cetuximab was successfully characterized using Normal phase high-performance liquid chromatography (NP-HPLC) in combination with Matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS). 28072827 1 15 theme biopharmaceutical 181:197 arg1 industries 199:208 biopharmaceutical industries 181:208 biopharmaceutical industries 181:208 Monitoring glycosylation of the mAbs have been emphasized and routinely characterized in biopharmaceutical industries because the carbohydrate components are closely related to the safety, efficacy, and consistency of the antibodies. 28072827 2 16 theme laser 550:554 arg1 MALDI-MS 597:604 MALDI-MS 597:604 MALDI-MS 597:604 In this study, the comprehensive glycan profiling of a biosimilar candidate of cetuximab was successfully characterized using Normal phase high-performance liquid chromatography (NP-HPLC) in combination with Matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS). 28072827 2 16 theme laser 550:554 arg1 spectrometry 583:594 Matrix assisted laser desorption/ionization mass spectrometry 534:594 Matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS) 534:605 In this study, the comprehensive glycan profiling of a biosimilar candidate of cetuximab was successfully characterized using Normal phase high-performance liquid chromatography (NP-HPLC) in combination with Matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS). 28072827 3 17 link N-linked 630:637 arg1 glycans 639:645 minor N-linked glycans 624:645 minor N-linked glycans containing sialic acid lactone residues (NeuAcLac) 624:696 The presence of minor N-linked glycans containing sialic acid lactone residues (NeuAcLac) was observed in the biosimilar for the first time, which could influence the quantitative analysis of sialylated glycans and interfere with quantification of neutral glycans when it was analyzed by high performance liquid chromatography fluorescence (HPLC-FL). 28072827 2 18 theme liquid 482:487 arg1 NP-HPLC 505:511 NP-HPLC 505:511 NP-HPLC 505:511 In this study, the comprehensive glycan profiling of a biosimilar candidate of cetuximab was successfully characterized using Normal phase high-performance liquid chromatography (NP-HPLC) in combination with Matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS). 28072827 2 18 theme liquid 482:487 arg1 chromatography 489:502 Normal phase high-performance liquid chromatography 452:502 Normal phase high-performance liquid chromatography (NP-HPLC) 452:512 In this study, the comprehensive glycan profiling of a biosimilar candidate of cetuximab was successfully characterized using Normal phase high-performance liquid chromatography (NP-HPLC) in combination with Matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS). 28072827 2 19 theme cetuximab 405:413 arg1 candidate 392:400 a biosimilar candidate 379:400 a biosimilar candidate of cetuximab 379:413 In this study, the comprehensive glycan profiling of a biosimilar candidate of cetuximab was successfully characterized using Normal phase high-performance liquid chromatography (NP-HPLC) in combination with Matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS). 28072827 0 20 theme N-Glycan 14:21 arg1 Profiling 23:31 Comprehensive N-Glycan Profiling 0:31 Comprehensive N-Glycan Profiling of Cetuximab Biosimilar Candidate by NP-HPLC and MALDI-MS. 0:90 Comprehensive N-Glycan Profiling of Cetuximab Biosimilar Candidate by NP-HPLC and MALDI-MS. 28072827 1 21 theme Monitoring 92:101 arg1 glycosylation 103:115 Monitoring glycosylation 92:115 Monitoring glycosylation of the mAbs 92:127 Monitoring glycosylation of the mAbs have been emphasized and routinely characterized in biopharmaceutical industries because the carbohydrate components are closely related to the safety, efficacy, and consistency of the antibodies. 28072827 0 22 theme Comprehensive 0:12 arg1 Profiling 23:31 Comprehensive N-Glycan Profiling 0:31 Comprehensive N-Glycan Profiling of Cetuximab Biosimilar Candidate by NP-HPLC and MALDI-MS. 0:90 Comprehensive N-Glycan Profiling of Cetuximab Biosimilar Candidate by NP-HPLC and MALDI-MS. 28072827 3 23 theme minor 624:628 arg1 glycans 639:645 minor N-linked glycans 624:645 minor N-linked glycans containing sialic acid lactone residues (NeuAcLac) 624:696 The presence of minor N-linked glycans containing sialic acid lactone residues (NeuAcLac) was observed in the biosimilar for the first time, which could influence the quantitative analysis of sialylated glycans and interfere with quantification of neutral glycans when it was analyzed by high performance liquid chromatography fluorescence (HPLC-FL). 28072827 4 24 theme glycans 1127:1133 arg1 analysis 1109:1116 the analysis 1105:1116 the analysis of other glycans 1105:1133 To overcome this issue, mild alkali treatment was used to hydrolyze lactone of the sialic acid to their neutral formation, which had no impact on the analysis of other glycans before and after the treatment. 28072827 2 25 theme candidate 392:400 arg1 profiling 366:374 the comprehensive glycan profiling 341:374 the comprehensive glycan profiling of a biosimilar candidate of cetuximab 341:413 In this study, the comprehensive glycan profiling of a biosimilar candidate of cetuximab was successfully characterized using Normal phase high-performance liquid chromatography (NP-HPLC) in combination with Matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS). 28072827 2 26 theme high-performance 465:480 arg1 NP-HPLC 505:511 NP-HPLC 505:511 NP-HPLC 505:511 In this study, the comprehensive glycan profiling of a biosimilar candidate of cetuximab was successfully characterized using Normal phase high-performance liquid chromatography (NP-HPLC) in combination with Matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS). 28072827 2 26 theme high-performance 465:480 arg1 chromatography 489:502 Normal phase high-performance liquid chromatography 452:502 Normal phase high-performance liquid chromatography (NP-HPLC) 452:512 In this study, the comprehensive glycan profiling of a biosimilar candidate of cetuximab was successfully characterized using Normal phase high-performance liquid chromatography (NP-HPLC) in combination with Matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS). 28072827 3 27 theme sialylated 800:809 arg1 glycans 811:817 sialylated glycans 800:817 sialylated glycans 800:817 The presence of minor N-linked glycans containing sialic acid lactone residues (NeuAcLac) was observed in the biosimilar for the first time, which could influence the quantitative analysis of sialylated glycans and interfere with quantification of neutral glycans when it was analyzed by high performance liquid chromatography fluorescence (HPLC-FL). 28072827 4 28 theme other 1121:1125 arg1 glycans 1127:1133 other glycans 1121:1133 other glycans 1121:1133 To overcome this issue, mild alkali treatment was used to hydrolyze lactone of the sialic acid to their neutral formation, which had no impact on the analysis of other glycans before and after the treatment. 28072827 2 29 theme Normal 452:457 arg1 NP-HPLC 505:511 NP-HPLC 505:511 NP-HPLC 505:511 In this study, the comprehensive glycan profiling of a biosimilar candidate of cetuximab was successfully characterized using Normal phase high-performance liquid chromatography (NP-HPLC) in combination with Matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS). 28072827 2 29 theme Normal 452:457 arg1 chromatography 489:502 Normal phase high-performance liquid chromatography 452:502 Normal phase high-performance liquid chromatography (NP-HPLC) 452:512 In this study, the comprehensive glycan profiling of a biosimilar candidate of cetuximab was successfully characterized using Normal phase high-performance liquid chromatography (NP-HPLC) in combination with Matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS). 28072827 2 30 theme phase 459:463 arg1 NP-HPLC 505:511 NP-HPLC 505:511 NP-HPLC 505:511 In this study, the comprehensive glycan profiling of a biosimilar candidate of cetuximab was successfully characterized using Normal phase high-performance liquid chromatography (NP-HPLC) in combination with Matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS). 28072827 2 30 theme phase 459:463 arg1 chromatography 489:502 Normal phase high-performance liquid chromatography 452:502 Normal phase high-performance liquid chromatography (NP-HPLC) 452:512 In this study, the comprehensive glycan profiling of a biosimilar candidate of cetuximab was successfully characterized using Normal phase high-performance liquid chromatography (NP-HPLC) in combination with Matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS). 28072827 3 31 theme quantitative 775:786 arg1 analysis 788:795 the quantitative analysis 771:795 the quantitative analysis of sialylated glycans 771:817 The presence of minor N-linked glycans containing sialic acid lactone residues (NeuAcLac) was observed in the biosimilar for the first time, which could influence the quantitative analysis of sialylated glycans and interfere with quantification of neutral glycans when it was analyzed by high performance liquid chromatography fluorescence (HPLC-FL). 28072827 4 32 from impact 1095:1100 arg1 analysis 1109:1116 the analysis 1105:1116 the analysis of other glycans 1105:1133 To overcome this issue, mild alkali treatment was used to hydrolyze lactone of the sialic acid to their neutral formation, which had no impact on the analysis of other glycans before and after the treatment. 28072827 0 33 theme Biosimilar 46:55 arg1 Candidate 57:65 Cetuximab Biosimilar Candidate 36:65 Cetuximab Biosimilar Candidate 36:65 Comprehensive N-Glycan Profiling of Cetuximab Biosimilar Candidate by NP-HPLC and MALDI-MS. 28072827 1 34 theme antibodies 314:323 arg1 efficacy 281:288 efficacy 281:288 efficacy 281:288 Monitoring glycosylation of the mAbs have been emphasized and routinely characterized in biopharmaceutical industries because the carbohydrate components are closely related to the safety, efficacy, and consistency of the antibodies. 28072827 1 34 theme antibodies 314:323 arg1 consistency 295:305 consistency 295:305 consistency 295:305 Monitoring glycosylation of the mAbs have been emphasized and routinely characterized in biopharmaceutical industries because the carbohydrate components are closely related to the safety, efficacy, and consistency of the antibodies. 28072827 1 34 theme antibodies 314:323 arg1 safety 273:278 safety 273:278 safety 273:278 Monitoring glycosylation of the mAbs have been emphasized and routinely characterized in biopharmaceutical industries because the carbohydrate components are closely related to the safety, efficacy, and consistency of the antibodies. 28072827 4 35 theme mild 983:986 arg1 treatment 995:1003 mild alkali treatment 983:1003 mild alkali treatment 983:1003 To overcome this issue, mild alkali treatment was used to hydrolyze lactone of the sialic acid to their neutral formation, which had no impact on the analysis of other glycans before and after the treatment. 28072827 5 36 theme mAbs 1270:1273 arg1 drugs 1275:1279 the mAbs drugs 1266:1279 the mAbs drugs with enhanced accuracy and robustness 1266:1317 As a result, the mild alkali treatment might be helpful to obtain quantitative glycan profiling of the mAbs drugs with enhanced accuracy and robustness. 28072827 0 37 theme Cetuximab 36:44 arg1 Candidate 57:65 Cetuximab Biosimilar Candidate 36:65 Cetuximab Biosimilar Candidate 36:65 Comprehensive N-Glycan Profiling of Cetuximab Biosimilar Candidate by NP-HPLC and MALDI-MS. 28072827 4 38 theme acid 1049:1052 arg1 lactone 1027:1033 lactone 1027:1033 lactone of the sialic acid to their neutral formation, which had no impact on the analysis of other glycans before and after the treatment 1027:1164 To overcome this issue, mild alkali treatment was used to hydrolyze lactone of the sialic acid to their neutral formation, which had no impact on the analysis of other glycans before and after the treatment. 28072827 3 39 theme sialic 658:663 arg1 NeuAcLac 688:695 NeuAcLac 688:695 NeuAcLac 688:695 The presence of minor N-linked glycans containing sialic acid lactone residues (NeuAcLac) was observed in the biosimilar for the first time, which could influence the quantitative analysis of sialylated glycans and interfere with quantification of neutral glycans when it was analyzed by high performance liquid chromatography fluorescence (HPLC-FL). 28072827 3 39 theme sialic 658:663 arg1 residues 678:685 sialic acid lactone residues 658:685 sialic acid lactone residues (NeuAcLac) 658:696 The presence of minor N-linked glycans containing sialic acid lactone residues (NeuAcLac) was observed in the biosimilar for the first time, which could influence the quantitative analysis of sialylated glycans and interfere with quantification of neutral glycans when it was analyzed by high performance liquid chromatography fluorescence (HPLC-FL). 28072827 5 40 theme mild 1184:1187 arg1 helpful 1215:1221 helpful 1215:1221 helpful 1215:1221 As a result, the mild alkali treatment might be helpful to obtain quantitative glycan profiling of the mAbs drugs with enhanced accuracy and robustness. 28072827 5 40 theme mild 1184:1187 arg1 treatment 1196:1204 the mild alkali treatment 1180:1204 the mild alkali treatment 1180:1204 As a result, the mild alkali treatment might be helpful to obtain quantitative glycan profiling of the mAbs drugs with enhanced accuracy and robustness. 28072827 3 41 theme N-linked 630:637 arg1 glycans 639:645 minor N-linked glycans 624:645 minor N-linked glycans containing sialic acid lactone residues (NeuAcLac) 624:696 The presence of minor N-linked glycans containing sialic acid lactone residues (NeuAcLac) was observed in the biosimilar for the first time, which could influence the quantitative analysis of sialylated glycans and interfere with quantification of neutral glycans when it was analyzed by high performance liquid chromatography fluorescence (HPLC-FL). 28072827 1 42 theme mAbs 124:127 arg1 glycosylation 103:115 Monitoring glycosylation 92:115 Monitoring glycosylation of the mAbs 92:127 Monitoring glycosylation of the mAbs have been emphasized and routinely characterized in biopharmaceutical industries because the carbohydrate components are closely related to the safety, efficacy, and consistency of the antibodies. 28072827 0 43 theme Candidate 57:65 arg1 Profiling 23:31 Comprehensive N-Glycan Profiling 0:31 Comprehensive N-Glycan Profiling of Cetuximab Biosimilar Candidate by NP-HPLC and MALDI-MS. 0:90 Comprehensive N-Glycan Profiling of Cetuximab Biosimilar Candidate by NP-HPLC and MALDI-MS. 28072827 3 44 theme glycans 811:817 arg1 analysis 788:795 the quantitative analysis 771:795 the quantitative analysis of sialylated glycans 771:817 The presence of minor N-linked glycans containing sialic acid lactone residues (NeuAcLac) was observed in the biosimilar for the first time, which could influence the quantitative analysis of sialylated glycans and interfere with quantification of neutral glycans when it was analyzed by high performance liquid chromatography fluorescence (HPLC-FL). 28072827 3 45 theme glycans 639:645 arg1 presence 612:619 The presence 608:619 The presence of minor N-linked glycans containing sialic acid lactone residues (NeuAcLac) 608:696 The presence of minor N-linked glycans containing sialic acid lactone residues (NeuAcLac) was observed in the biosimilar for the first time, which could influence the quantitative analysis of sialylated glycans and interfere with quantification of neutral glycans when it was analyzed by high performance liquid chromatography fluorescence (HPLC-FL). 28072827 2 46 theme comprehensive 345:357 arg1 profiling 366:374 the comprehensive glycan profiling 341:374 the comprehensive glycan profiling of a biosimilar candidate of cetuximab 341:413 In this study, the comprehensive glycan profiling of a biosimilar candidate of cetuximab was successfully characterized using Normal phase high-performance liquid chromatography (NP-HPLC) in combination with Matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS). 28072827 3 47 theme performance 901:911 arg1 chromatography 920:933 high performance liquid chromatography 896:933 high performance liquid chromatography fluorescence (HPLC-FL) 896:956 The presence of minor N-linked glycans containing sialic acid lactone residues (NeuAcLac) was observed in the biosimilar for the first time, which could influence the quantitative analysis of sialylated glycans and interfere with quantification of neutral glycans when it was analyzed by high performance liquid chromatography fluorescence (HPLC-FL). 28072827 5 48 theme quantitative 1233:1244 arg1 profiling 1253:1261 quantitative glycan profiling 1233:1261 quantitative glycan profiling of the mAbs drugs with enhanced accuracy and robustness 1233:1317 As a result, the mild alkali treatment might be helpful to obtain quantitative glycan profiling of the mAbs drugs with enhanced accuracy and robustness. 28072827 4 49 used used 1009:1012 arg2 treatment 995:1003 mild alkali treatment 983:1003 mild alkali treatment 983:1003 To overcome this issue, mild alkali treatment was used to hydrolyze lactone of the sialic acid to their neutral formation, which had no impact on the analysis of other glycans before and after the treatment. 28072827 3 50 theme liquid 913:918 arg1 chromatography 920:933 high performance liquid chromatography 896:933 high performance liquid chromatography fluorescence (HPLC-FL) 896:956 The presence of minor N-linked glycans containing sialic acid lactone residues (NeuAcLac) was observed in the biosimilar for the first time, which could influence the quantitative analysis of sialylated glycans and interfere with quantification of neutral glycans when it was analyzed by high performance liquid chromatography fluorescence (HPLC-FL). 28072827 3 51 theme neutral 856:862 arg1 glycans 864:870 neutral glycans 856:870 neutral glycans 856:870 The presence of minor N-linked glycans containing sialic acid lactone residues (NeuAcLac) was observed in the biosimilar for the first time, which could influence the quantitative analysis of sialylated glycans and interfere with quantification of neutral glycans when it was analyzed by high performance liquid chromatography fluorescence (HPLC-FL). 28072827 5 52 theme enhanced 1286:1293 arg1 accuracy 1295:1302 enhanced accuracy 1286:1302 enhanced accuracy 1286:1302 As a result, the mild alkali treatment might be helpful to obtain quantitative glycan profiling of the mAbs drugs with enhanced accuracy and robustness. 28072827 3 53 theme glycans 864:870 arg1 quantification 838:851 quantification 838:851 quantification of neutral glycans 838:870 The presence of minor N-linked glycans containing sialic acid lactone residues (NeuAcLac) was observed in the biosimilar for the first time, which could influence the quantitative analysis of sialylated glycans and interfere with quantification of neutral glycans when it was analyzed by high performance liquid chromatography fluorescence (HPLC-FL). 28072827 2 54 theme assisted 541:548 arg1 MALDI-MS 597:604 MALDI-MS 597:604 MALDI-MS 597:604 In this study, the comprehensive glycan profiling of a biosimilar candidate of cetuximab was successfully characterized using Normal phase high-performance liquid chromatography (NP-HPLC) in combination with Matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS). 28072827 2 54 theme assisted 541:548 arg1 spectrometry 583:594 Matrix assisted laser desorption/ionization mass spectrometry 534:594 Matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS) 534:605 In this study, the comprehensive glycan profiling of a biosimilar candidate of cetuximab was successfully characterized using Normal phase high-performance liquid chromatography (NP-HPLC) in combination with Matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS). 28072827 3 55 theme acid 665:668 arg1 NeuAcLac 688:695 NeuAcLac 688:695 NeuAcLac 688:695 The presence of minor N-linked glycans containing sialic acid lactone residues (NeuAcLac) was observed in the biosimilar for the first time, which could influence the quantitative analysis of sialylated glycans and interfere with quantification of neutral glycans when it was analyzed by high performance liquid chromatography fluorescence (HPLC-FL). 28072827 3 55 theme acid 665:668 arg1 residues 678:685 sialic acid lactone residues 658:685 sialic acid lactone residues (NeuAcLac) 658:696 The presence of minor N-linked glycans containing sialic acid lactone residues (NeuAcLac) was observed in the biosimilar for the first time, which could influence the quantitative analysis of sialylated glycans and interfere with quantification of neutral glycans when it was analyzed by high performance liquid chromatography fluorescence (HPLC-FL). 28072827 1 56 theme carbohydrate 222:233 arg1 components 235:244 the carbohydrate components 218:244 the carbohydrate components 218:244 Monitoring glycosylation of the mAbs have been emphasized and routinely characterized in biopharmaceutical industries because the carbohydrate components are closely related to the safety, efficacy, and consistency of the antibodies. 28072827 1 56 theme carbohydrate 222:233 arg1 related 258:264 related 258:264 related 258:264 Monitoring glycosylation of the mAbs have been emphasized and routinely characterized in biopharmaceutical industries because the carbohydrate components are closely related to the safety, efficacy, and consistency of the antibodies. 28072827 2 57 theme biosimilar 381:390 arg1 candidate 392:400 a biosimilar candidate 379:400 a biosimilar candidate of cetuximab 379:413 In this study, the comprehensive glycan profiling of a biosimilar candidate of cetuximab was successfully characterized using Normal phase high-performance liquid chromatography (NP-HPLC) in combination with Matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS). 28072827 3 58 theme high 896:899 arg1 chromatography 920:933 high performance liquid chromatography 896:933 high performance liquid chromatography fluorescence (HPLC-FL) 896:956 The presence of minor N-linked glycans containing sialic acid lactone residues (NeuAcLac) was observed in the biosimilar for the first time, which could influence the quantitative analysis of sialylated glycans and interfere with quantification of neutral glycans when it was analyzed by high performance liquid chromatography fluorescence (HPLC-FL). 28072827 5 59 theme glycan 1246:1251 arg1 profiling 1253:1261 quantitative glycan profiling 1233:1261 quantitative glycan profiling of the mAbs drugs with enhanced accuracy and robustness 1233:1317 As a result, the mild alkali treatment might be helpful to obtain quantitative glycan profiling of the mAbs drugs with enhanced accuracy and robustness. 28072827 2 60 theme Matrix 534:539 arg1 MALDI-MS 597:604 MALDI-MS 597:604 MALDI-MS 597:604 In this study, the comprehensive glycan profiling of a biosimilar candidate of cetuximab was successfully characterized using Normal phase high-performance liquid chromatography (NP-HPLC) in combination with Matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS). 28072827 2 60 theme Matrix 534:539 arg1 spectrometry 583:594 Matrix assisted laser desorption/ionization mass spectrometry 534:594 Matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS) 534:605 In this study, the comprehensive glycan profiling of a biosimilar candidate of cetuximab was successfully characterized using Normal phase high-performance liquid chromatography (NP-HPLC) in combination with Matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS). 28072827 3 61 theme lactone 670:676 arg1 NeuAcLac 688:695 NeuAcLac 688:695 NeuAcLac 688:695 The presence of minor N-linked glycans containing sialic acid lactone residues (NeuAcLac) was observed in the biosimilar for the first time, which could influence the quantitative analysis of sialylated glycans and interfere with quantification of neutral glycans when it was analyzed by high performance liquid chromatography fluorescence (HPLC-FL). 28072827 3 61 theme lactone 670:676 arg1 residues 678:685 sialic acid lactone residues 658:685 sialic acid lactone residues (NeuAcLac) 658:696 The presence of minor N-linked glycans containing sialic acid lactone residues (NeuAcLac) was observed in the biosimilar for the first time, which could influence the quantitative analysis of sialylated glycans and interfere with quantification of neutral glycans when it was analyzed by high performance liquid chromatography fluorescence (HPLC-FL). 28072827 4 62 theme neutral 1063:1069 arg1 formation 1071:1079 their neutral formation 1057:1079 their neutral formation 1057:1079 To overcome this issue, mild alkali treatment was used to hydrolyze lactone of the sialic acid to their neutral formation, which had no impact on the analysis of other glycans before and after the treatment. 28072827 4 63 theme alkali 988:993 arg1 treatment 995:1003 mild alkali treatment 983:1003 mild alkali treatment 983:1003 To overcome this issue, mild alkali treatment was used to hydrolyze lactone of the sialic acid to their neutral formation, which had no impact on the analysis of other glycans before and after the treatment. 27624811 8 0 theme Campylobacter 1359:1371 arg1 jejuni 1373:1378 Campylobacter jejuni 1359:1378 Campylobacter jejuni 1359:1378 Activity and kinetic parameters of PglC, a PGT from Campylobacter jejuni, were quickly established using this assay. 27624811 5 1 theme new 960:962 arg1 UMP-Glo 990:996 UMP-Glo 990:996 UMP-Glo 990:996 Herein, we present the validation of a new luminescence-based assay (UMP-Glo) for measuring activities of PGT enzymes. 27624811 5 1 theme new 960:962 arg1 assay 983:987 a new luminescence-based assay 958:987 a new luminescence-based assay (UMP-Glo) for measuring activities of PGT enzymes 958:1037 Herein, we present the validation of a new luminescence-based assay (UMP-Glo) for measuring activities of PGT enzymes. 27624811 9 2 theme different 1485:1493 arg1 WecA 1537:1540 WecA 1537:1540 WecA from Thermatoga maritima 1537:1565 The efficacy of the assay was further corroborated using two different PGTs; PglC from Helicobacter pullorum and WecA from Thermatoga maritima. 27624811 9 2 theme different 1485:1493 arg1 PglC 1501:1504 PglC 1501:1504 PglC from Helicobacter pullorum 1501:1531 The efficacy of the assay was further corroborated using two different PGTs; PglC from Helicobacter pullorum and WecA from Thermatoga maritima. 27624811 9 2 theme different 1485:1493 arg1 PGTs 1495:1498 two different PGTs 1481:1498 two different PGTs; PglC from Helicobacter pullorum and WecA from Thermatoga maritima 1481:1565 The efficacy of the assay was further corroborated using two different PGTs; PglC from Helicobacter pullorum and WecA from Thermatoga maritima. 27624811 9 3 from maritima 1558:1565 arg1 WecA 1537:1540 WecA 1537:1540 WecA from Thermatoga maritima 1537:1565 The efficacy of the assay was further corroborated using two different PGTs; PglC from Helicobacter pullorum and WecA from Thermatoga maritima. 27624811 9 3 from maritima 1558:1565 arg1 PglC 1501:1504 PglC 1501:1504 PglC from Helicobacter pullorum 1501:1531 The efficacy of the assay was further corroborated using two different PGTs; PglC from Helicobacter pullorum and WecA from Thermatoga maritima. 27624811 9 3 from maritima 1558:1565 arg1 PGTs 1495:1498 two different PGTs 1481:1498 two different PGTs; PglC from Helicobacter pullorum and WecA from Thermatoga maritima 1481:1565 The efficacy of the assay was further corroborated using two different PGTs; PglC from Helicobacter pullorum and WecA from Thermatoga maritima. 27624811 1 4 theme diverse 193:199 arg1 architectures 201:213 intriguingly diverse architectures 180:213 intriguingly diverse architectures 180:213 Phosphoglycosyltransferases (PGTs) are families of integral membrane proteins with intriguingly diverse architectures. 27624811 9 5 theme assay 1444:1448 arg1 efficacy 1428:1435 The efficacy 1424:1435 The efficacy of the assay 1424:1448 The efficacy of the assay was further corroborated using two different PGTs; PglC from Helicobacter pullorum and WecA from Thermatoga maritima. 27624811 2 6 gly glycoproteins 339:351 arg1 glycoproteins 339:351 N-linked glycoproteins 330:351 N-linked glycoproteins 330:351 These enzymes function to initiate many important biosynthetic pathways including those leading to peptidoglycan, N-linked glycoproteins and lipopolysaccharide O-antigen. 27624811 4 7 theme low 905:907 arg1 throughput 909:918 low throughput 905:918 low throughput 905:918 Current PGT assays include radioactivity-based methods, which rely on liquid-liquid or solid-liquid extractions, multienzyme systems linked to lactate dehydrogenase and NAD(+) generation, and HPLC-based approaches, all of which may suffer from low sensitivity and low throughput. 27624811 5 8 theme PGT 1027:1029 arg1 enzymes 1031:1037 PGT enzymes 1027:1037 PGT enzymes 1027:1037 Herein, we present the validation of a new luminescence-based assay (UMP-Glo) for measuring activities of PGT enzymes. 27624811 6 9 theme coupled 1193:1199 arg1 system 1207:1212 a discontinuous coupled assay system 1177:1212 a discontinuous coupled assay system 1177:1212 This assay measures UMP, the by-product of PGT reactions, in a sensitive and quantitative manner by measuring the luminescence output in a discontinuous coupled assay system. 27624811 5 10 theme enzymes 1031:1037 arg1 activities 1013:1022 activities 1013:1022 activities of PGT enzymes 1013:1037 Herein, we present the validation of a new luminescence-based assay (UMP-Glo) for measuring activities of PGT enzymes. 27624811 7 11 theme microtiter 1281:1290 arg1 formats 1298:1304 microtiter plate formats 1281:1304 microtiter plate formats 1281:1304 The assay is rapid and robust in nature, and also compatible with microtiter plate formats. 27624811 3 12 theme convenient 622:631 arg1 assays 633:638 convenient assays 622:638 convenient assays 622:638 In spite of tremendous efforts, characterization of these enzymes remains a challenge not only due to the inherent difficulties associated with the purification of integral membrane proteins but also due to the limited availability of convenient assays. 27624811 3 13 theme membrane 560:567 arg1 proteins 569:576 integral membrane proteins 551:576 integral membrane proteins 551:576 In spite of tremendous efforts, characterization of these enzymes remains a challenge not only due to the inherent difficulties associated with the purification of integral membrane proteins but also due to the limited availability of convenient assays. 27624811 5 14 theme assay 983:987 arg1 validation 944:953 the validation 940:953 the validation of a new luminescence-based assay (UMP-Glo) for measuring activities of PGT enzymes 940:1037 Herein, we present the validation of a new luminescence-based assay (UMP-Glo) for measuring activities of PGT enzymes. 27624811 6 15 from measures 1051:1058 arg1 manner 1130:1135 a sensitive and quantitative manner 1101:1135 a sensitive and quantitative manner 1101:1135 This assay measures UMP, the by-product of PGT reactions, in a sensitive and quantitative manner by measuring the luminescence output in a discontinuous coupled assay system. 27624811 4 16 theme liquid-liquid 711:723 arg1 extractions 741:751 liquid-liquid or solid-liquid extractions 711:751 liquid-liquid or solid-liquid extractions 711:751 Current PGT assays include radioactivity-based methods, which rely on liquid-liquid or solid-liquid extractions, multienzyme systems linked to lactate dehydrogenase and NAD(+) generation, and HPLC-based approaches, all of which may suffer from low sensitivity and low throughput. 27624811 2 17 theme N-linked 330:337 arg1 glycoproteins 339:351 N-linked glycoproteins 330:351 N-linked glycoproteins 330:351 These enzymes function to initiate many important biosynthetic pathways including those leading to peptidoglycan, N-linked glycoproteins and lipopolysaccharide O-antigen. 27624811 4 18 theme multienzyme 754:764 arg1 systems 766:772 multienzyme systems 754:772 multienzyme systems linked to lactate dehydrogenase and NAD(+) generation 754:826 Current PGT assays include radioactivity-based methods, which rely on liquid-liquid or solid-liquid extractions, multienzyme systems linked to lactate dehydrogenase and NAD(+) generation, and HPLC-based approaches, all of which may suffer from low sensitivity and low throughput. 27624811 4 19 theme radioactivity-based 668:686 arg1 methods 688:694 radioactivity-based methods 668:694 radioactivity-based methods 668:694 Current PGT assays include radioactivity-based methods, which rely on liquid-liquid or solid-liquid extractions, multienzyme systems linked to lactate dehydrogenase and NAD(+) generation, and HPLC-based approaches, all of which may suffer from low sensitivity and low throughput. 27624811 6 20 theme assay 1201:1205 arg1 system 1207:1212 a discontinuous coupled assay system 1177:1212 a discontinuous coupled assay system 1177:1212 This assay measures UMP, the by-product of PGT reactions, in a sensitive and quantitative manner by measuring the luminescence output in a discontinuous coupled assay system. 27624811 6 21 theme quantitative 1117:1128 arg1 manner 1130:1135 a sensitive and quantitative manner 1101:1135 a sensitive and quantitative manner 1101:1135 This assay measures UMP, the by-product of PGT reactions, in a sensitive and quantitative manner by measuring the luminescence output in a discontinuous coupled assay system. 27624811 0 22 theme Rapid 2:6 arg1 Method 41:46 A Rapid and Efficient Luminescence-based Method 0:46 A Rapid and Efficient Luminescence-based Method for Assaying Phosphoglycosyltransferase Enzymes. 0:95 A Rapid and Efficient Luminescence-based Method for Assaying Phosphoglycosyltransferase Enzymes. 27624811 7 23 from rapid 1228:1232 arg1 nature 1248:1253 nature 1248:1253 nature 1248:1253 The assay is rapid and robust in nature, and also compatible with microtiter plate formats. 27624811 1 24 with families 136:143 arg1 architectures 201:213 intriguingly diverse architectures 180:213 intriguingly diverse architectures 180:213 Phosphoglycosyltransferases (PGTs) are families of integral membrane proteins with intriguingly diverse architectures. 27624811 2 25 dep peptidoglycan 315:327 arg1 O-antigen 376:384 O-antigen 376:384 O-antigen 376:384 These enzymes function to initiate many important biosynthetic pathways including those leading to peptidoglycan, N-linked glycoproteins and lipopolysaccharide O-antigen. 27624811 2 26 link N-linked 330:337 arg1 glycoproteins 339:351 N-linked glycoproteins 330:351 N-linked glycoproteins 330:351 These enzymes function to initiate many important biosynthetic pathways including those leading to peptidoglycan, N-linked glycoproteins and lipopolysaccharide O-antigen. 27624811 3 27 theme inherent 493:500 arg1 difficulties 502:513 the inherent difficulties 489:513 the inherent difficulties associated with the purification of integral membrane proteins 489:576 In spite of tremendous efforts, characterization of these enzymes remains a challenge not only due to the inherent difficulties associated with the purification of integral membrane proteins but also due to the limited availability of convenient assays. 27624811 3 28 theme enzymes 445:451 arg1 characterization 419:434 characterization 419:434 characterization of these enzymes 419:451 In spite of tremendous efforts, characterization of these enzymes remains a challenge not only due to the inherent difficulties associated with the purification of integral membrane proteins but also due to the limited availability of convenient assays. 27624811 8 29 theme PglC 1342:1345 arg1 Activity 1307:1314 Activity 1307:1314 Activity 1307:1314 Activity and kinetic parameters of PglC, a PGT from Campylobacter jejuni, were quickly established using this assay. 27624811 8 29 theme PglC 1342:1345 arg1 parameters 1328:1337 kinetic parameters 1320:1337 kinetic parameters 1320:1337 Activity and kinetic parameters of PglC, a PGT from Campylobacter jejuni, were quickly established using this assay. 27624811 9 30 from pullorum 1524:1531 arg1 WecA 1537:1540 WecA 1537:1540 WecA from Thermatoga maritima 1537:1565 The efficacy of the assay was further corroborated using two different PGTs; PglC from Helicobacter pullorum and WecA from Thermatoga maritima. 27624811 9 30 from pullorum 1524:1531 arg1 PglC 1501:1504 PglC 1501:1504 PglC from Helicobacter pullorum 1501:1531 The efficacy of the assay was further corroborated using two different PGTs; PglC from Helicobacter pullorum and WecA from Thermatoga maritima. 27624811 9 30 from pullorum 1524:1531 arg1 PGTs 1495:1498 two different PGTs 1481:1498 two different PGTs; PglC from Helicobacter pullorum and WecA from Thermatoga maritima 1481:1565 The efficacy of the assay was further corroborated using two different PGTs; PglC from Helicobacter pullorum and WecA from Thermatoga maritima. 27624811 3 31 theme assays 633:638 arg1 availability 606:617 the limited availability 594:617 the limited availability of convenient assays 594:638 In spite of tremendous efforts, characterization of these enzymes remains a challenge not only due to the inherent difficulties associated with the purification of integral membrane proteins but also due to the limited availability of convenient assays. 27624811 4 32 theme PGT 649:651 arg1 assays 653:658 Current PGT assays 641:658 Current PGT assays 641:658 Current PGT assays include radioactivity-based methods, which rely on liquid-liquid or solid-liquid extractions, multienzyme systems linked to lactate dehydrogenase and NAD(+) generation, and HPLC-based approaches, all of which may suffer from low sensitivity and low throughput. 27624811 3 33 theme limited 598:604 arg1 availability 606:617 the limited availability 594:617 the limited availability of convenient assays 594:638 In spite of tremendous efforts, characterization of these enzymes remains a challenge not only due to the inherent difficulties associated with the purification of integral membrane proteins but also due to the limited availability of convenient assays. 27624811 5 34 theme luminescence-based 964:981 arg1 UMP-Glo 990:996 UMP-Glo 990:996 UMP-Glo 990:996 Herein, we present the validation of a new luminescence-based assay (UMP-Glo) for measuring activities of PGT enzymes. 27624811 5 34 theme luminescence-based 964:981 arg1 assay 983:987 a new luminescence-based assay 958:987 a new luminescence-based assay (UMP-Glo) for measuring activities of PGT enzymes 958:1037 Herein, we present the validation of a new luminescence-based assay (UMP-Glo) for measuring activities of PGT enzymes. 27624811 4 35 theme lactate 784:790 arg1 dehydrogenase 792:804 lactate dehydrogenase 784:804 lactate dehydrogenase 784:804 Current PGT assays include radioactivity-based methods, which rely on liquid-liquid or solid-liquid extractions, multienzyme systems linked to lactate dehydrogenase and NAD(+) generation, and HPLC-based approaches, all of which may suffer from low sensitivity and low throughput. 27624811 4 36 theme Current 641:647 arg1 assays 653:658 Current PGT assays 641:658 Current PGT assays 641:658 Current PGT assays include radioactivity-based methods, which rely on liquid-liquid or solid-liquid extractions, multienzyme systems linked to lactate dehydrogenase and NAD(+) generation, and HPLC-based approaches, all of which may suffer from low sensitivity and low throughput. 27624811 7 37 theme plate 1292:1296 arg1 formats 1298:1304 microtiter plate formats 1281:1304 microtiter plate formats 1281:1304 The assay is rapid and robust in nature, and also compatible with microtiter plate formats. 27624811 7 38 from nature 1248:1253 arg1 assay 1219:1223 The assay 1215:1223 The assay 1215:1223 The assay is rapid and robust in nature, and also compatible with microtiter plate formats. 27624811 7 38 from nature 1248:1253 arg1 rapid 1228:1232 rapid 1228:1232 rapid 1228:1232 The assay is rapid and robust in nature, and also compatible with microtiter plate formats. 27624811 6 39 theme sensitive 1103:1111 arg1 manner 1130:1135 a sensitive and quantitative manner 1101:1135 a sensitive and quantitative manner 1101:1135 This assay measures UMP, the by-product of PGT reactions, in a sensitive and quantitative manner by measuring the luminescence output in a discontinuous coupled assay system. 27624811 8 40 theme kinetic 1320:1326 arg1 parameters 1328:1337 kinetic parameters 1320:1337 kinetic parameters 1320:1337 Activity and kinetic parameters of PglC, a PGT from Campylobacter jejuni, were quickly established using this assay. 27624811 0 41 theme Luminescence-based 22:39 arg1 Method 41:46 A Rapid and Efficient Luminescence-based Method 0:46 A Rapid and Efficient Luminescence-based Method for Assaying Phosphoglycosyltransferase Enzymes. 0:95 A Rapid and Efficient Luminescence-based Method for Assaying Phosphoglycosyltransferase Enzymes. 27624811 0 42 theme Efficient 12:20 arg1 Method 41:46 A Rapid and Efficient Luminescence-based Method 0:46 A Rapid and Efficient Luminescence-based Method for Assaying Phosphoglycosyltransferase Enzymes. 0:95 A Rapid and Efficient Luminescence-based Method for Assaying Phosphoglycosyltransferase Enzymes. 27624811 4 43 theme solid-liquid 728:739 arg1 extractions 741:751 liquid-liquid or solid-liquid extractions 711:751 liquid-liquid or solid-liquid extractions 711:751 Current PGT assays include radioactivity-based methods, which rely on liquid-liquid or solid-liquid extractions, multienzyme systems linked to lactate dehydrogenase and NAD(+) generation, and HPLC-based approaches, all of which may suffer from low sensitivity and low throughput. 27624811 4 44 attach linked 774:779 arg1 dehydrogenase 792:804 lactate dehydrogenase 784:804 lactate dehydrogenase 784:804 Current PGT assays include radioactivity-based methods, which rely on liquid-liquid or solid-liquid extractions, multienzyme systems linked to lactate dehydrogenase and NAD(+) generation, and HPLC-based approaches, all of which may suffer from low sensitivity and low throughput. 27624811 4 44 attach linked 774:779 arg1 generation 817:826 NAD(+) generation 810:826 NAD(+) generation 810:826 Current PGT assays include radioactivity-based methods, which rely on liquid-liquid or solid-liquid extractions, multienzyme systems linked to lactate dehydrogenase and NAD(+) generation, and HPLC-based approaches, all of which may suffer from low sensitivity and low throughput. 27624811 4 44 attach linked 774:779 arg2 systems 766:772 multienzyme systems 754:772 multienzyme systems linked to lactate dehydrogenase and NAD(+) generation 754:826 Current PGT assays include radioactivity-based methods, which rely on liquid-liquid or solid-liquid extractions, multienzyme systems linked to lactate dehydrogenase and NAD(+) generation, and HPLC-based approaches, all of which may suffer from low sensitivity and low throughput. 27624811 2 45 theme biosynthetic 266:277 arg1 pathways 279:286 many important biosynthetic pathways 251:286 many important biosynthetic pathways including those leading to peptidoglycan, N-linked glycoproteins and lipopolysaccharide O-antigen 251:384 These enzymes function to initiate many important biosynthetic pathways including those leading to peptidoglycan, N-linked glycoproteins and lipopolysaccharide O-antigen. 27624811 2 45 theme biosynthetic 266:277 arg1 those 298:302 those 298:302 those 298:302 These enzymes function to initiate many important biosynthetic pathways including those leading to peptidoglycan, N-linked glycoproteins and lipopolysaccharide O-antigen. 27624811 6 46 theme luminescence 1154:1165 arg1 output 1167:1172 the luminescence output 1150:1172 the luminescence output in a discontinuous coupled assay system 1150:1212 This assay measures UMP, the by-product of PGT reactions, in a sensitive and quantitative manner by measuring the luminescence output in a discontinuous coupled assay system. 27624811 3 47 theme proteins 569:576 arg1 purification 535:546 the purification 531:546 the purification of integral membrane proteins 531:576 In spite of tremendous efforts, characterization of these enzymes remains a challenge not only due to the inherent difficulties associated with the purification of integral membrane proteins but also due to the limited availability of convenient assays. 27624811 2 48 theme many 251:254 arg1 pathways 279:286 many important biosynthetic pathways 251:286 many important biosynthetic pathways including those leading to peptidoglycan, N-linked glycoproteins and lipopolysaccharide O-antigen 251:384 These enzymes function to initiate many important biosynthetic pathways including those leading to peptidoglycan, N-linked glycoproteins and lipopolysaccharide O-antigen. 27624811 2 48 theme many 251:254 arg1 those 298:302 those 298:302 those 298:302 These enzymes function to initiate many important biosynthetic pathways including those leading to peptidoglycan, N-linked glycoproteins and lipopolysaccharide O-antigen. 27624811 2 49 theme important 256:264 arg1 pathways 279:286 many important biosynthetic pathways 251:286 many important biosynthetic pathways including those leading to peptidoglycan, N-linked glycoproteins and lipopolysaccharide O-antigen 251:384 These enzymes function to initiate many important biosynthetic pathways including those leading to peptidoglycan, N-linked glycoproteins and lipopolysaccharide O-antigen. 27624811 2 49 theme important 256:264 arg1 those 298:302 those 298:302 those 298:302 These enzymes function to initiate many important biosynthetic pathways including those leading to peptidoglycan, N-linked glycoproteins and lipopolysaccharide O-antigen. 27624811 4 50 theme NAD 810:812 arg1 generation 817:826 NAD(+) generation 810:826 NAD(+) generation 810:826 Current PGT assays include radioactivity-based methods, which rely on liquid-liquid or solid-liquid extractions, multienzyme systems linked to lactate dehydrogenase and NAD(+) generation, and HPLC-based approaches, all of which may suffer from low sensitivity and low throughput. 27624811 6 51 from output 1167:1172 arg1 system 1207:1212 a discontinuous coupled assay system 1177:1212 a discontinuous coupled assay system 1177:1212 This assay measures UMP, the by-product of PGT reactions, in a sensitive and quantitative manner by measuring the luminescence output in a discontinuous coupled assay system. 27624811 4 52 theme low 885:887 arg1 sensitivity 889:899 low sensitivity 885:899 low sensitivity 885:899 Current PGT assays include radioactivity-based methods, which rely on liquid-liquid or solid-liquid extractions, multienzyme systems linked to lactate dehydrogenase and NAD(+) generation, and HPLC-based approaches, all of which may suffer from low sensitivity and low throughput. 27624811 1 53 theme integral 148:155 arg1 proteins 166:173 integral membrane proteins 148:173 integral membrane proteins 148:173 Phosphoglycosyltransferases (PGTs) are families of integral membrane proteins with intriguingly diverse architectures. 27624811 4 54 theme HPLC-based 833:842 arg1 approaches 844:853 HPLC-based approaches 833:853 HPLC-based approaches 833:853 Current PGT assays include radioactivity-based methods, which rely on liquid-liquid or solid-liquid extractions, multienzyme systems linked to lactate dehydrogenase and NAD(+) generation, and HPLC-based approaches, all of which may suffer from low sensitivity and low throughput. 27624811 6 55 theme PGT 1083:1085 arg1 reactions 1087:1095 PGT reactions 1083:1095 PGT reactions 1083:1095 This assay measures UMP, the by-product of PGT reactions, in a sensitive and quantitative manner by measuring the luminescence output in a discontinuous coupled assay system. 27624811 1 56 theme membrane 157:164 arg1 proteins 166:173 integral membrane proteins 148:173 integral membrane proteins 148:173 Phosphoglycosyltransferases (PGTs) are families of integral membrane proteins with intriguingly diverse architectures. 27624811 6 57 theme discontinuous 1179:1191 arg1 system 1207:1212 a discontinuous coupled assay system 1177:1212 a discontinuous coupled assay system 1177:1212 This assay measures UMP, the by-product of PGT reactions, in a sensitive and quantitative manner by measuring the luminescence output in a discontinuous coupled assay system. 27624811 3 58 theme integral 551:558 arg1 proteins 569:576 integral membrane proteins 551:576 integral membrane proteins 551:576 In spite of tremendous efforts, characterization of these enzymes remains a challenge not only due to the inherent difficulties associated with the purification of integral membrane proteins but also due to the limited availability of convenient assays. 27624811 3 59 theme tremendous 399:408 arg1 efforts 410:416 tremendous efforts 399:416 tremendous efforts 399:416 In spite of tremendous efforts, characterization of these enzymes remains a challenge not only due to the inherent difficulties associated with the purification of integral membrane proteins but also due to the limited availability of convenient assays. 27624811 6 60 theme reactions 1087:1095 arg1 UMP 1060:1062 UMP 1060:1062 UMP 1060:1062 This assay measures UMP, the by-product of PGT reactions, in a sensitive and quantitative manner by measuring the luminescence output in a discontinuous coupled assay system. 27624811 6 60 theme reactions 1087:1095 arg1 by-product 1069:1078 the by-product 1065:1078 the by-product of PGT reactions 1065:1095 This assay measures UMP, the by-product of PGT reactions, in a sensitive and quantitative manner by measuring the luminescence output in a discontinuous coupled assay system. 27624811 9 61 dep PGTs 1495:1498 arg1 WecA 1537:1540 WecA 1537:1540 WecA from Thermatoga maritima 1537:1565 The efficacy of the assay was further corroborated using two different PGTs; PglC from Helicobacter pullorum and WecA from Thermatoga maritima. 27624811 9 61 dep PGTs 1495:1498 arg1 PglC 1501:1504 PglC 1501:1504 PglC from Helicobacter pullorum 1501:1531 The efficacy of the assay was further corroborated using two different PGTs; PglC from Helicobacter pullorum and WecA from Thermatoga maritima. 27624811 9 61 dep PGTs 1495:1498 arg1 PGTs 1495:1498 two different PGTs 1481:1498 two different PGTs; PglC from Helicobacter pullorum and WecA from Thermatoga maritima 1481:1565 The efficacy of the assay was further corroborated using two different PGTs; PglC from Helicobacter pullorum and WecA from Thermatoga maritima. 27624811 1 62 theme proteins 166:173 arg1 families 136:143 families 136:143 families of integral membrane proteins with intriguingly diverse architectures 136:213 Phosphoglycosyltransferases (PGTs) are families of integral membrane proteins with intriguingly diverse architectures. 27624811 1 62 theme proteins 166:173 arg1 Phosphoglycosyltransferases 97:123 Phosphoglycosyltransferases 97:123 Phosphoglycosyltransferases (PGTs) 97:130 Phosphoglycosyltransferases (PGTs) are families of integral membrane proteins with intriguingly diverse architectures. 27624811 8 63 from jejuni 1373:1378 arg1 PglC 1342:1345 PglC 1342:1345 PglC 1342:1345 Activity and kinetic parameters of PglC, a PGT from Campylobacter jejuni, were quickly established using this assay. 27624811 8 63 from jejuni 1373:1378 arg1 PGT 1350:1352 a PGT 1348:1352 a PGT from Campylobacter jejuni 1348:1378 Activity and kinetic parameters of PglC, a PGT from Campylobacter jejuni, were quickly established using this assay. 27624811 0 64 theme Phosphoglycosyltransferase 61:86 arg1 Enzymes 88:94 Phosphoglycosyltransferase Enzymes 61:94 Phosphoglycosyltransferase Enzymes 61:94 A Rapid and Efficient Luminescence-based Method for Assaying Phosphoglycosyltransferase Enzymes. 27624811 7 65 with compatible 1265:1274 arg1 formats 1298:1304 microtiter plate formats 1281:1304 microtiter plate formats 1281:1304 The assay is rapid and robust in nature, and also compatible with microtiter plate formats. 27624811 9 66 theme Thermatoga 1547:1556 arg1 maritima 1558:1565 Thermatoga maritima 1547:1565 Thermatoga maritima 1547:1565 The efficacy of the assay was further corroborated using two different PGTs; PglC from Helicobacter pullorum and WecA from Thermatoga maritima. 26201970 0 0 theme sting 80:84 arg1 dermatitis 86:95 sting dermatitis 80:95 sting dermatitis 80:95 Identification of allergens in the box jellyfish Chironex yamaguchii that cause sting dermatitis. 26201970 6 1 link N-linked 1058:1065 arg1 glycoprotein 1067:1078 an asparagine residue-coupled N-linked glycoprotein 1028:1078 an asparagine residue-coupled N-linked glycoprotein 1028:1078 In addition, the 66-kDa protein was found to be an asparagine residue-coupled N-linked glycoprotein and the epitope resided in the protein fraction. 26201970 6 1 link N-linked 1058:1065 arg1 protein 1004:1010 the 66-kDa protein 993:1010 the 66-kDa protein 993:1010 In addition, the 66-kDa protein was found to be an asparagine residue-coupled N-linked glycoprotein and the epitope resided in the protein fraction. 26201970 4 2 from controls 800:807 arg1 sera 763:766 sera 763:766 sera from 1 patient and from several controls 763:807 METHODS We comprehensively studied the immunoglobulin-binding molecules from the box jellyfish C. yamaguchii with a purification procedure and Western blotting, using sera from 1 patient and from several controls. 26201970 1 3 theme due 170:172 arg1 eruptions 160:168 painful, papular-urticarial eruptions 132:168 painful, papular-urticarial eruptions due to the immediate allergic, acute toxic and persistent inflammatory responses 132:249 BACKGROUND Jellyfish stings cause painful, papular-urticarial eruptions due to the immediate allergic, acute toxic and persistent inflammatory responses. 26201970 6 4 theme 66-kDa 997:1002 arg1 glycoprotein 1067:1078 an asparagine residue-coupled N-linked glycoprotein 1028:1078 an asparagine residue-coupled N-linked glycoprotein 1028:1078 In addition, the 66-kDa protein was found to be an asparagine residue-coupled N-linked glycoprotein and the epitope resided in the protein fraction. 26201970 6 4 theme 66-kDa 997:1002 arg1 protein 1004:1010 the 66-kDa protein 993:1010 the 66-kDa protein 993:1010 In addition, the 66-kDa protein was found to be an asparagine residue-coupled N-linked glycoprotein and the epitope resided in the protein fraction. 26201970 8 5 from extracts 1314:1321 arg1 blot 1288:1291 Western blot 1280:1291 Western blot from both nematocyst extracts and purified CqTX-A 1280:1341 This was confirmed as a 45-kDa protein by Western blot from both nematocyst extracts and purified CqTX-A. 26201970 9 6 theme immediate 1423:1431 arg1 responses 1472:1480 the combined immediate allergic-toxic and persistent allergic responses 1410:1480 the combined immediate allergic-toxic and persistent allergic responses 1410:1480 CONCLUSIONS The detection of these proteins may, in part, explain the combined immediate allergic-toxic and persistent allergic responses. 26201970 3 7 theme jellyfish 502:510 arg1 yamaguchii 521:530 the box jellyfish Chironex yamaguchii 494:530 the box jellyfish Chironex yamaguchii 494:530 The purpose of this study was to define the specific allergen of the box jellyfish Chironex yamaguchii and to study the precise mechanism of the resulting dermatitis. 26201970 10 8 theme specific 1539:1546 arg1 immunotherapy 1554:1566 specific venom immunotherapy 1539:1566 specific venom immunotherapy for marine professional workers and tourists for jellyfish-sting dermatitis and anaphylaxis 1539:1658 Hopefully, our findings will lead to the development of specific venom immunotherapy for marine professional workers and tourists for jellyfish-sting dermatitis and anaphylaxis. 26201970 6 9 theme N-linked 1058:1065 arg1 glycoprotein 1067:1078 an asparagine residue-coupled N-linked glycoprotein 1028:1078 an asparagine residue-coupled N-linked glycoprotein 1028:1078 In addition, the 66-kDa protein was found to be an asparagine residue-coupled N-linked glycoprotein and the epitope resided in the protein fraction. 26201970 6 9 theme N-linked 1058:1065 arg1 protein 1004:1010 the 66-kDa protein 993:1010 the 66-kDa protein 993:1010 In addition, the 66-kDa protein was found to be an asparagine residue-coupled N-linked glycoprotein and the epitope resided in the protein fraction. 26201970 7 10 theme nematocyst 1182:1191 arg1 CqTX-A 1143:1148 CqTX-A 1143:1148 CqTX-A 1143:1148 We found that CqTX-A, the major toxic protein of the nematocyst, is also a heat-stable IgE-binding allergen. 26201970 7 10 theme nematocyst 1182:1191 arg1 protein 1167:1173 the major toxic protein 1151:1173 the major toxic protein of the nematocyst 1151:1191 We found that CqTX-A, the major toxic protein of the nematocyst, is also a heat-stable IgE-binding allergen. 26201970 0 11 from Identification 0:13 arg1 yamaguchii 58:67 the box jellyfish Chironex yamaguchii 31:67 the box jellyfish Chironex yamaguchii that cause sting dermatitis 31:95 Identification of allergens in the box jellyfish Chironex yamaguchii that cause sting dermatitis. 26201970 1 12 dep painful 132:138 arg1 papular-urticarial 141:158 papular-urticarial 141:158 papular-urticarial 141:158 BACKGROUND Jellyfish stings cause painful, papular-urticarial eruptions due to the immediate allergic, acute toxic and persistent inflammatory responses. 26201970 10 13 theme immunotherapy 1554:1566 arg1 development 1524:1534 the development 1520:1534 the development of specific venom immunotherapy for marine professional workers and tourists for jellyfish-sting dermatitis and anaphylaxis 1520:1658 Hopefully, our findings will lead to the development of specific venom immunotherapy for marine professional workers and tourists for jellyfish-sting dermatitis and anaphylaxis. 26201970 5 14 gly glycoprotein 885:896 arg1 glycoprotein 885:896 IgG-binding acidic glycoprotein 866:896 IgG-binding acidic glycoprotein (of 66 and 30 kDa) 866:915 RESULTS From the nematocyst wall and spine, we detected IgG-binding acidic glycoprotein (of 66 and 30 kDa) as determined by Western blot and ion-exchange chromatography. 26201970 2 15 theme specific 366:373 arg1 allergen 375:382 specific allergen 366:382 specific allergen 366:382 In spite of many marine accidents and their economic impact, modes of first-aid treatment remain conventional and specific allergen and medical treatment are not yet available. 26201970 4 16 from yamaguchii 694:703 arg1 molecules 658:666 the immunoglobulin-binding molecules 631:666 the immunoglobulin-binding molecules from the box jellyfish C. yamaguchii with a purification procedure and Western blotting 631:754 METHODS We comprehensively studied the immunoglobulin-binding molecules from the box jellyfish C. yamaguchii with a purification procedure and Western blotting, using sera from 1 patient and from several controls. 26201970 6 17 theme protein 1111:1117 arg1 fraction 1119:1126 the protein fraction 1107:1126 the protein fraction 1107:1126 In addition, the 66-kDa protein was found to be an asparagine residue-coupled N-linked glycoprotein and the epitope resided in the protein fraction. 26201970 4 18 theme purification 712:723 arg1 procedure 725:733 a purification procedure 710:733 a purification procedure 710:733 METHODS We comprehensively studied the immunoglobulin-binding molecules from the box jellyfish C. yamaguchii with a purification procedure and Western blotting, using sera from 1 patient and from several controls. 26201970 5 19 theme kDa 912:914 arg1 glycoprotein 885:896 IgG-binding acidic glycoprotein 866:896 IgG-binding acidic glycoprotein (of 66 and 30 kDa) 866:915 RESULTS From the nematocyst wall and spine, we detected IgG-binding acidic glycoprotein (of 66 and 30 kDa) as determined by Western blot and ion-exchange chromatography. 26201970 5 20 dep RESULTS 810:816 arg1 detected 857:864 detected 857:864 detected IgG-binding acidic glycoprotein (of 66 and 30 kDa) as determined by Western blot and ion-exchange chromatography 857:977 RESULTS From the nematocyst wall and spine, we detected IgG-binding acidic glycoprotein (of 66 and 30 kDa) as determined by Western blot and ion-exchange chromatography. 26201970 4 21 from patient 775:781 arg1 sera 763:766 sera 763:766 sera from 1 patient and from several controls 763:807 METHODS We comprehensively studied the immunoglobulin-binding molecules from the box jellyfish C. yamaguchii with a purification procedure and Western blotting, using sera from 1 patient and from several controls. 26201970 4 22 theme several 792:798 arg1 controls 800:807 several controls 792:807 several controls 792:807 METHODS We comprehensively studied the immunoglobulin-binding molecules from the box jellyfish C. yamaguchii with a purification procedure and Western blotting, using sera from 1 patient and from several controls. 26201970 9 23 theme combined 1414:1421 arg1 responses 1472:1480 the combined immediate allergic-toxic and persistent allergic responses 1410:1480 the combined immediate allergic-toxic and persistent allergic responses 1410:1480 CONCLUSIONS The detection of these proteins may, in part, explain the combined immediate allergic-toxic and persistent allergic responses. 26201970 4 24 theme jellyfish 681:689 arg1 yamaguchii 694:703 the box jellyfish C. yamaguchii 673:703 the box jellyfish C. yamaguchii 673:703 METHODS We comprehensively studied the immunoglobulin-binding molecules from the box jellyfish C. yamaguchii with a purification procedure and Western blotting, using sera from 1 patient and from several controls. 26201970 9 25 theme allergic-toxic 1433:1446 arg1 responses 1472:1480 the combined immediate allergic-toxic and persistent allergic responses 1410:1480 the combined immediate allergic-toxic and persistent allergic responses 1410:1480 CONCLUSIONS The detection of these proteins may, in part, explain the combined immediate allergic-toxic and persistent allergic responses. 26201970 8 26 theme purified 1327:1334 arg1 CqTX-A 1336:1341 purified CqTX-A 1327:1341 purified CqTX-A 1327:1341 This was confirmed as a 45-kDa protein by Western blot from both nematocyst extracts and purified CqTX-A. 26201970 1 27 theme immediate 181:189 arg1 responses 241:249 the immediate allergic, acute toxic and persistent inflammatory responses 177:249 the immediate allergic, acute toxic and persistent inflammatory responses 177:249 BACKGROUND Jellyfish stings cause painful, papular-urticarial eruptions due to the immediate allergic, acute toxic and persistent inflammatory responses. 26201970 2 28 theme economic 296:303 arg1 impact 305:310 their economic impact 290:310 their economic impact 290:310 In spite of many marine accidents and their economic impact, modes of first-aid treatment remain conventional and specific allergen and medical treatment are not yet available. 26201970 9 29 dep CONCLUSIONS 1344:1354 arg1 detection 1360:1368 The detection 1356:1368 CONCLUSIONS The detection of these proteins 1344:1386 CONCLUSIONS The detection of these proteins may, in part, explain the combined immediate allergic-toxic and persistent allergic responses. 26201970 4 30 theme box 677:679 arg1 yamaguchii 694:703 the box jellyfish C. yamaguchii 673:703 the box jellyfish C. yamaguchii 673:703 METHODS We comprehensively studied the immunoglobulin-binding molecules from the box jellyfish C. yamaguchii with a purification procedure and Western blotting, using sera from 1 patient and from several controls. 26201970 6 31 located found 1016:1020 arg2 glycoprotein 1067:1078 an asparagine residue-coupled N-linked glycoprotein 1028:1078 an asparagine residue-coupled N-linked glycoprotein 1028:1078 In addition, the 66-kDa protein was found to be an asparagine residue-coupled N-linked glycoprotein and the epitope resided in the protein fraction. 26201970 6 31 located found 1016:1020 arg1 addition 983:990 addition 983:990 addition 983:990 In addition, the 66-kDa protein was found to be an asparagine residue-coupled N-linked glycoprotein and the epitope resided in the protein fraction. 26201970 6 31 located found 1016:1020 arg2 protein 1004:1010 the 66-kDa protein 993:1010 the 66-kDa protein 993:1010 In addition, the 66-kDa protein was found to be an asparagine residue-coupled N-linked glycoprotein and the epitope resided in the protein fraction. 26201970 7 32 theme toxic 1161:1165 arg1 CqTX-A 1143:1148 CqTX-A 1143:1148 CqTX-A 1143:1148 We found that CqTX-A, the major toxic protein of the nematocyst, is also a heat-stable IgE-binding allergen. 26201970 7 32 theme toxic 1161:1165 arg1 protein 1167:1173 the major toxic protein 1151:1173 the major toxic protein of the nematocyst 1151:1191 We found that CqTX-A, the major toxic protein of the nematocyst, is also a heat-stable IgE-binding allergen. 26201970 1 33 theme allergic 191:198 arg1 responses 241:249 the immediate allergic, acute toxic and persistent inflammatory responses 177:249 the immediate allergic, acute toxic and persistent inflammatory responses 177:249 BACKGROUND Jellyfish stings cause painful, papular-urticarial eruptions due to the immediate allergic, acute toxic and persistent inflammatory responses. 26201970 5 34 theme nematocyst 827:836 arg1 wall 838:841 the nematocyst wall 823:841 the nematocyst wall 823:841 RESULTS From the nematocyst wall and spine, we detected IgG-binding acidic glycoprotein (of 66 and 30 kDa) as determined by Western blot and ion-exchange chromatography. 26201970 5 35 theme Western 934:940 arg1 blot 942:945 Western blot 934:945 Western blot 934:945 RESULTS From the nematocyst wall and spine, we detected IgG-binding acidic glycoprotein (of 66 and 30 kDa) as determined by Western blot and ion-exchange chromatography. 26201970 2 36 theme medical 388:394 arg1 treatment 396:404 medical treatment 388:404 medical treatment 388:404 In spite of many marine accidents and their economic impact, modes of first-aid treatment remain conventional and specific allergen and medical treatment are not yet available. 26201970 10 37 theme professional 1579:1590 arg1 workers 1592:1598 marine professional workers 1572:1598 marine professional workers 1572:1598 Hopefully, our findings will lead to the development of specific venom immunotherapy for marine professional workers and tourists for jellyfish-sting dermatitis and anaphylaxis. 26201970 8 38 theme Western 1280:1286 arg1 blot 1288:1291 Western blot 1280:1291 Western blot from both nematocyst extracts and purified CqTX-A 1280:1341 This was confirmed as a 45-kDa protein by Western blot from both nematocyst extracts and purified CqTX-A. 26201970 1 39 theme BACKGROUND 98:107 arg1 stings 119:124 BACKGROUND Jellyfish stings 98:124 BACKGROUND Jellyfish stings 98:124 BACKGROUND Jellyfish stings cause painful, papular-urticarial eruptions due to the immediate allergic, acute toxic and persistent inflammatory responses. 26201970 5 40 theme ion-exchange 951:962 arg1 chromatography 964:977 ion-exchange chromatography 951:977 ion-exchange chromatography 951:977 RESULTS From the nematocyst wall and spine, we detected IgG-binding acidic glycoprotein (of 66 and 30 kDa) as determined by Western blot and ion-exchange chromatography. 26201970 0 41 theme allergens 18:26 arg1 Identification 0:13 Identification 0:13 Identification of allergens in the box jellyfish Chironex yamaguchii that cause sting dermatitis. 0:96 Identification of allergens in the box jellyfish Chironex yamaguchii that cause sting dermatitis. 26201970 4 42 dep METHODS 596:602 arg1 studied 623:629 studied 623:629 studied 623:629 METHODS We comprehensively studied the immunoglobulin-binding molecules from the box jellyfish C. yamaguchii with a purification procedure and Western blotting, using sera from 1 patient and from several controls. 26201970 1 43 theme Jellyfish 109:117 arg1 stings 119:124 BACKGROUND Jellyfish stings 98:124 BACKGROUND Jellyfish stings 98:124 BACKGROUND Jellyfish stings cause painful, papular-urticarial eruptions due to the immediate allergic, acute toxic and persistent inflammatory responses. 26201970 4 44 theme immunoglobulin-binding 635:656 arg1 molecules 658:666 the immunoglobulin-binding molecules 631:666 the immunoglobulin-binding molecules from the box jellyfish C. yamaguchii with a purification procedure and Western blotting 631:754 METHODS We comprehensively studied the immunoglobulin-binding molecules from the box jellyfish C. yamaguchii with a purification procedure and Western blotting, using sera from 1 patient and from several controls. 26201970 0 45 theme box 35:37 arg1 yamaguchii 58:67 the box jellyfish Chironex yamaguchii 31:67 the box jellyfish Chironex yamaguchii that cause sting dermatitis 31:95 Identification of allergens in the box jellyfish Chironex yamaguchii that cause sting dermatitis. 26201970 10 46 theme marine 1572:1577 arg1 workers 1592:1598 marine professional workers 1572:1598 marine professional workers 1572:1598 Hopefully, our findings will lead to the development of specific venom immunotherapy for marine professional workers and tourists for jellyfish-sting dermatitis and anaphylaxis. 26201970 1 47 dep allergic 191:198 arg1 toxic 207:211 toxic 207:211 toxic 207:211 BACKGROUND Jellyfish stings cause painful, papular-urticarial eruptions due to the immediate allergic, acute toxic and persistent inflammatory responses. 26201970 1 47 dep allergic 191:198 arg1 persistent 217:226 persistent 217:226 persistent 217:226 BACKGROUND Jellyfish stings cause painful, papular-urticarial eruptions due to the immediate allergic, acute toxic and persistent inflammatory responses. 26201970 4 48 theme C. 691:692 arg1 yamaguchii 694:703 the box jellyfish C. yamaguchii 673:703 the box jellyfish C. yamaguchii 673:703 METHODS We comprehensively studied the immunoglobulin-binding molecules from the box jellyfish C. yamaguchii with a purification procedure and Western blotting, using sera from 1 patient and from several controls. 26201970 9 49 theme persistent 1452:1461 arg1 responses 1472:1480 the combined immediate allergic-toxic and persistent allergic responses 1410:1480 the combined immediate allergic-toxic and persistent allergic responses 1410:1480 CONCLUSIONS The detection of these proteins may, in part, explain the combined immediate allergic-toxic and persistent allergic responses. 26201970 5 50 theme IgG-binding 866:876 arg1 glycoprotein 885:896 IgG-binding acidic glycoprotein 866:896 IgG-binding acidic glycoprotein (of 66 and 30 kDa) 866:915 RESULTS From the nematocyst wall and spine, we detected IgG-binding acidic glycoprotein (of 66 and 30 kDa) as determined by Western blot and ion-exchange chromatography. 26201970 5 51 theme acidic 878:883 arg1 glycoprotein 885:896 IgG-binding acidic glycoprotein 866:896 IgG-binding acidic glycoprotein (of 66 and 30 kDa) 866:915 RESULTS From the nematocyst wall and spine, we detected IgG-binding acidic glycoprotein (of 66 and 30 kDa) as determined by Western blot and ion-exchange chromatography. 26201970 10 52 theme jellyfish-sting 1617:1631 arg1 dermatitis 1633:1642 jellyfish-sting dermatitis 1617:1642 jellyfish-sting dermatitis 1617:1642 Hopefully, our findings will lead to the development of specific venom immunotherapy for marine professional workers and tourists for jellyfish-sting dermatitis and anaphylaxis. 26201970 9 53 theme allergic 1463:1470 arg1 responses 1472:1480 the combined immediate allergic-toxic and persistent allergic responses 1410:1480 the combined immediate allergic-toxic and persistent allergic responses 1410:1480 CONCLUSIONS The detection of these proteins may, in part, explain the combined immediate allergic-toxic and persistent allergic responses. 26201970 0 54 theme Chironex 49:56 arg1 yamaguchii 58:67 the box jellyfish Chironex yamaguchii 31:67 the box jellyfish Chironex yamaguchii that cause sting dermatitis 31:95 Identification of allergens in the box jellyfish Chironex yamaguchii that cause sting dermatitis. 26201970 3 55 theme box 498:500 arg1 yamaguchii 521:530 the box jellyfish Chironex yamaguchii 494:530 the box jellyfish Chironex yamaguchii 494:530 The purpose of this study was to define the specific allergen of the box jellyfish Chironex yamaguchii and to study the precise mechanism of the resulting dermatitis. 26201970 3 56 theme resulting 574:582 arg1 dermatitis 584:593 the resulting dermatitis 570:593 the resulting dermatitis 570:593 The purpose of this study was to define the specific allergen of the box jellyfish Chironex yamaguchii and to study the precise mechanism of the resulting dermatitis. 26201970 4 57 theme Western 739:745 arg1 blotting 747:754 Western blotting 739:754 Western blotting 739:754 METHODS We comprehensively studied the immunoglobulin-binding molecules from the box jellyfish C. yamaguchii with a purification procedure and Western blotting, using sera from 1 patient and from several controls. 26201970 0 58 theme jellyfish 39:47 arg1 yamaguchii 58:67 the box jellyfish Chironex yamaguchii 31:67 the box jellyfish Chironex yamaguchii that cause sting dermatitis 31:95 Identification of allergens in the box jellyfish Chironex yamaguchii that cause sting dermatitis. 26201970 3 59 theme specific 473:480 arg1 allergen 482:489 the specific allergen 469:489 the specific allergen of the box jellyfish Chironex yamaguchii 469:530 The purpose of this study was to define the specific allergen of the box jellyfish Chironex yamaguchii and to study the precise mechanism of the resulting dermatitis. 26201970 3 60 theme dermatitis 584:593 arg1 mechanism 557:565 the precise mechanism 545:565 the precise mechanism of the resulting dermatitis 545:593 The purpose of this study was to define the specific allergen of the box jellyfish Chironex yamaguchii and to study the precise mechanism of the resulting dermatitis. 26201970 7 61 theme major 1155:1159 arg1 CqTX-A 1143:1148 CqTX-A 1143:1148 CqTX-A 1143:1148 We found that CqTX-A, the major toxic protein of the nematocyst, is also a heat-stable IgE-binding allergen. 26201970 7 61 theme major 1155:1159 arg1 protein 1167:1173 the major toxic protein 1151:1173 the major toxic protein of the nematocyst 1151:1191 We found that CqTX-A, the major toxic protein of the nematocyst, is also a heat-stable IgE-binding allergen. 26201970 8 62 theme 45-kDa 1262:1267 arg1 This 1238:1241 This 1238:1241 This 1238:1241 This was confirmed as a 45-kDa protein by Western blot from both nematocyst extracts and purified CqTX-A. 26201970 8 62 theme 45-kDa 1262:1267 arg1 protein 1269:1275 a 45-kDa protein 1260:1275 a 45-kDa protein 1260:1275 This was confirmed as a 45-kDa protein by Western blot from both nematocyst extracts and purified CqTX-A. 26201970 8 63 from CqTX-A 1336:1341 arg1 blot 1288:1291 Western blot 1280:1291 Western blot from both nematocyst extracts and purified CqTX-A 1280:1341 This was confirmed as a 45-kDa protein by Western blot from both nematocyst extracts and purified CqTX-A. 26201970 2 64 theme marine 269:274 arg1 accidents 276:284 many marine accidents 264:284 many marine accidents 264:284 In spite of many marine accidents and their economic impact, modes of first-aid treatment remain conventional and specific allergen and medical treatment are not yet available. 26201970 1 65 theme painful 132:138 arg1 eruptions 160:168 painful, papular-urticarial eruptions 132:168 painful, papular-urticarial eruptions due to the immediate allergic, acute toxic and persistent inflammatory responses 132:249 BACKGROUND Jellyfish stings cause painful, papular-urticarial eruptions due to the immediate allergic, acute toxic and persistent inflammatory responses. 26201970 3 66 theme precise 549:555 arg1 mechanism 557:565 the precise mechanism 545:565 the precise mechanism of the resulting dermatitis 545:593 The purpose of this study was to define the specific allergen of the box jellyfish Chironex yamaguchii and to study the precise mechanism of the resulting dermatitis. 26201970 1 67 theme inflammatory 228:239 arg1 responses 241:249 the immediate allergic, acute toxic and persistent inflammatory responses 177:249 the immediate allergic, acute toxic and persistent inflammatory responses 177:249 BACKGROUND Jellyfish stings cause painful, papular-urticarial eruptions due to the immediate allergic, acute toxic and persistent inflammatory responses. 26201970 6 68 gly glycoprotein 1067:1078 arg1 glycoprotein 1067:1078 an asparagine residue-coupled N-linked glycoprotein 1028:1078 an asparagine residue-coupled N-linked glycoprotein 1028:1078 In addition, the 66-kDa protein was found to be an asparagine residue-coupled N-linked glycoprotein and the epitope resided in the protein fraction. 26201970 6 68 gly glycoprotein 1067:1078 arg1 protein 1004:1010 the 66-kDa protein 993:1010 the 66-kDa protein 993:1010 In addition, the 66-kDa protein was found to be an asparagine residue-coupled N-linked glycoprotein and the epitope resided in the protein fraction. 26201970 4 69 with molecules 658:666 arg1 procedure 725:733 a purification procedure 710:733 a purification procedure 710:733 METHODS We comprehensively studied the immunoglobulin-binding molecules from the box jellyfish C. yamaguchii with a purification procedure and Western blotting, using sera from 1 patient and from several controls. 26201970 4 69 with molecules 658:666 arg1 blotting 747:754 Western blotting 739:754 Western blotting 739:754 METHODS We comprehensively studied the immunoglobulin-binding molecules from the box jellyfish C. yamaguchii with a purification procedure and Western blotting, using sera from 1 patient and from several controls. 26201970 2 70 theme many 264:267 arg1 accidents 276:284 many marine accidents 264:284 many marine accidents 264:284 In spite of many marine accidents and their economic impact, modes of first-aid treatment remain conventional and specific allergen and medical treatment are not yet available. 26201970 10 71 theme venom 1548:1552 arg1 immunotherapy 1554:1566 specific venom immunotherapy 1539:1566 specific venom immunotherapy for marine professional workers and tourists for jellyfish-sting dermatitis and anaphylaxis 1539:1658 Hopefully, our findings will lead to the development of specific venom immunotherapy for marine professional workers and tourists for jellyfish-sting dermatitis and anaphylaxis. 26201970 2 72 theme first-aid 322:330 arg1 treatment 332:340 first-aid treatment 322:340 first-aid treatment 322:340 In spite of many marine accidents and their economic impact, modes of first-aid treatment remain conventional and specific allergen and medical treatment are not yet available. 26201970 8 73 theme nematocyst 1303:1312 arg1 extracts 1314:1321 nematocyst extracts 1303:1321 nematocyst extracts 1303:1321 This was confirmed as a 45-kDa protein by Western blot from both nematocyst extracts and purified CqTX-A. 26201970 2 74 theme treatment 332:340 arg1 modes 313:317 modes 313:317 modes of first-aid treatment 313:340 In spite of many marine accidents and their economic impact, modes of first-aid treatment remain conventional and specific allergen and medical treatment are not yet available. 26201970 6 75 theme residue-coupled 1042:1056 arg1 glycoprotein 1067:1078 an asparagine residue-coupled N-linked glycoprotein 1028:1078 an asparagine residue-coupled N-linked glycoprotein 1028:1078 In addition, the 66-kDa protein was found to be an asparagine residue-coupled N-linked glycoprotein and the epitope resided in the protein fraction. 26201970 6 75 theme residue-coupled 1042:1056 arg1 protein 1004:1010 the 66-kDa protein 993:1010 the 66-kDa protein 993:1010 In addition, the 66-kDa protein was found to be an asparagine residue-coupled N-linked glycoprotein and the epitope resided in the protein fraction. 26201970 3 76 theme Chironex 512:519 arg1 yamaguchii 521:530 the box jellyfish Chironex yamaguchii 494:530 the box jellyfish Chironex yamaguchii 494:530 The purpose of this study was to define the specific allergen of the box jellyfish Chironex yamaguchii and to study the precise mechanism of the resulting dermatitis. 26201970 3 77 theme study 449:453 arg1 purpose 433:439 The purpose 429:439 The purpose of this study 429:453 The purpose of this study was to define the specific allergen of the box jellyfish Chironex yamaguchii and to study the precise mechanism of the resulting dermatitis. 26201970 9 78 theme proteins 1379:1386 arg1 detection 1360:1368 The detection 1356:1368 CONCLUSIONS The detection of these proteins 1344:1386 CONCLUSIONS The detection of these proteins may, in part, explain the combined immediate allergic-toxic and persistent allergic responses. 26201970 7 79 theme heat-stable 1204:1214 arg1 CqTX-A 1143:1148 CqTX-A 1143:1148 CqTX-A 1143:1148 We found that CqTX-A, the major toxic protein of the nematocyst, is also a heat-stable IgE-binding allergen. 26201970 7 79 theme heat-stable 1204:1214 arg1 allergen 1228:1235 a heat-stable IgE-binding allergen 1202:1235 a heat-stable IgE-binding allergen 1202:1235 We found that CqTX-A, the major toxic protein of the nematocyst, is also a heat-stable IgE-binding allergen. 26201970 1 80 dep toxic 207:211 arg1 acute 201:205 acute 201:205 acute 201:205 BACKGROUND Jellyfish stings cause painful, papular-urticarial eruptions due to the immediate allergic, acute toxic and persistent inflammatory responses. 26201970 3 81 theme yamaguchii 521:530 arg1 allergen 482:489 the specific allergen 469:489 the specific allergen of the box jellyfish Chironex yamaguchii 469:530 The purpose of this study was to define the specific allergen of the box jellyfish Chironex yamaguchii and to study the precise mechanism of the resulting dermatitis. 26201970 7 82 theme IgE-binding 1216:1226 arg1 CqTX-A 1143:1148 CqTX-A 1143:1148 CqTX-A 1143:1148 We found that CqTX-A, the major toxic protein of the nematocyst, is also a heat-stable IgE-binding allergen. 26201970 7 82 theme IgE-binding 1216:1226 arg1 allergen 1228:1235 a heat-stable IgE-binding allergen 1202:1235 a heat-stable IgE-binding allergen 1202:1235 We found that CqTX-A, the major toxic protein of the nematocyst, is also a heat-stable IgE-binding allergen. 25670976 6 0 theme different 1070:1078 arg1 glycosides 1102:1111 the different S-linked and N-linked glycosides 1066:1111 the different S-linked and N-linked glycosides 1066:1111 The ability of the different S-linked and N-linked glycosides to inhibit the sialic acid transfer reaction from 3'-sialyllactose to the natural substrate N-acetyllactosamine, was also studied. 25670976 9 1 theme main 1684:1687 arg1 product 1689:1695 main product 1684:1695 main product 1684:1695 The usefulness of the enzymatic trans-sialylation for the preparation of sialylated ligands was assessed by performing a preparative sialylation of a divalent substrate, which afforded the monosialylated compound as main product, together with the disialylated glycocluster. 25670976 9 2 gly monosialylated 1657:1670 arg1 compound 1672:1679 the monosialylated compound 1653:1679 the monosialylated compound as main product 1653:1695 The usefulness of the enzymatic trans-sialylation for the preparation of sialylated ligands was assessed by performing a preparative sialylation of a divalent substrate, which afforded the monosialylated compound as main product, together with the disialylated glycocluster. 25670976 3 3 theme chemoenzymatic 678:691 arg1 synthesis 693:701 the chemoenzymatic synthesis 674:701 the chemoenzymatic synthesis of sialic acid containing glycoclusters 674:741 Herein, the enzyme was also tested as a tool for the chemoenzymatic synthesis of sialic acid containing glycoclusters. 25670976 4 4 theme sialic 844:849 arg1 donor 856:860 sialic acid donor 844:860 sialic acid donor 844:860 The transfer reaction of sialic acid was performed using a recombinant TcTS and 3'-sialyllactose as sialic acid donor, in the presence of the acceptor having βGalp non reducing ends. 25670976 6 5 theme transfer 1140:1147 arg1 reaction 1149:1156 the sialic acid transfer reaction 1124:1156 the sialic acid transfer reaction from 3'-sialyllactose to the natural substrate N-acetyllactosamine 1124:1223 The ability of the different S-linked and N-linked glycosides to inhibit the sialic acid transfer reaction from 3'-sialyllactose to the natural substrate N-acetyllactosamine, was also studied. 25670976 3 6 theme glycoclusters 729:741 arg1 synthesis 693:701 the chemoenzymatic synthesis 674:701 the chemoenzymatic synthesis of sialic acid containing glycoclusters 674:741 Herein, the enzyme was also tested as a tool for the chemoenzymatic synthesis of sialic acid containing glycoclusters. 25670976 4 7 theme acid 851:854 arg1 donor 856:860 sialic acid donor 844:860 sialic acid donor 844:860 The transfer reaction of sialic acid was performed using a recombinant TcTS and 3'-sialyllactose as sialic acid donor, in the presence of the acceptor having βGalp non reducing ends. 25670976 4 8 theme having 895:900 arg1 ends 921:924 the acceptor having βGalp non reducing ends 882:924 the acceptor having βGalp non reducing ends 882:924 The transfer reaction of sialic acid was performed using a recombinant TcTS and 3'-sialyllactose as sialic acid donor, in the presence of the acceptor having βGalp non reducing ends. 25670976 6 9 theme sialic 1128:1133 arg1 reaction 1149:1156 the sialic acid transfer reaction 1124:1156 the sialic acid transfer reaction from 3'-sialyllactose to the natural substrate N-acetyllactosamine 1124:1223 The ability of the different S-linked and N-linked glycosides to inhibit the sialic acid transfer reaction from 3'-sialyllactose to the natural substrate N-acetyllactosamine, was also studied. 25670976 3 10 theme acid 713:716 arg1 glycoclusters 729:741 sialic acid containing glycoclusters 706:741 sialic acid containing glycoclusters 706:741 Herein, the enzyme was also tested as a tool for the chemoenzymatic synthesis of sialic acid containing glycoclusters. 25670976 4 11 theme non 908:910 arg1 ends 921:924 the acceptor having βGalp non reducing ends 882:924 the acceptor having βGalp non reducing ends 882:924 The transfer reaction of sialic acid was performed using a recombinant TcTS and 3'-sialyllactose as sialic acid donor, in the presence of the acceptor having βGalp non reducing ends. 25670976 8 12 theme equimolar 1442:1450 arg1 concentration 1452:1464 equimolar concentration 1442:1464 equimolar concentration 1442:1464 A di-N-lactoside showed to be the strongest competitive inhibitor among the compounds tested (70% inhibition at equimolar concentration). 25670976 1 13 theme mono- 221:225 arg1 β-N- 240:243 mono- and divalent β-N- 221:243 mono- and divalent β-N- 221:243 In this work we describe the synthesis of mono- and divalent β-N- and β-S-galactopyranosides and related lactosides built on sugar scaffolds and their evaluation as substrates and inhibitors of the Trypanosoma cruzi trans-sialidase (TcTS). 25670976 0 14 theme cruzi 156:160 arg1 trans-sialidase 162:176 Trypanosoma cruzi trans-sialidase 144:176 Trypanosoma cruzi trans-sialidase 144:176 Synthesis of divalent ligands of β-thio- and β-N-galactopyranosides and related lactosides and their evaluation as substrates and inhibitors of Trypanosoma cruzi trans-sialidase. 25670976 9 15 theme trans-sialylation 1500:1516 arg1 usefulness 1472:1481 The usefulness 1468:1481 The usefulness of the enzymatic trans-sialylation for the preparation of sialylated ligands 1468:1558 The usefulness of the enzymatic trans-sialylation for the preparation of sialylated ligands was assessed by performing a preparative sialylation of a divalent substrate, which afforded the monosialylated compound as main product, together with the disialylated glycocluster. 25670976 6 16 theme natural 1187:1193 arg1 N-acetyllactosamine 1205:1223 the natural substrate N-acetyllactosamine 1183:1223 the natural substrate N-acetyllactosamine 1183:1223 The ability of the different S-linked and N-linked glycosides to inhibit the sialic acid transfer reaction from 3'-sialyllactose to the natural substrate N-acetyllactosamine, was also studied. 25670976 0 17 theme lactosides 80:89 arg1 ligands 22:28 divalent ligands 13:28 divalent ligands of β-thio- and β-N-galactopyranosides and related lactosides 13:89 Synthesis of divalent ligands of β-thio- and β-N-galactopyranosides and related lactosides and their evaluation as substrates and inhibitors of Trypanosoma cruzi trans-sialidase. 25670976 9 18 theme ligands 1552:1558 arg1 preparation 1526:1536 the preparation 1522:1536 the preparation of sialylated ligands 1522:1558 The usefulness of the enzymatic trans-sialylation for the preparation of sialylated ligands was assessed by performing a preparative sialylation of a divalent substrate, which afforded the monosialylated compound as main product, together with the disialylated glycocluster. 25670976 2 19 theme terminal 531:538 arg1 units 540:544 parasite βGalp terminal units 516:544 parasite βGalp terminal units 516:544 This enzyme catalyzes the transfer of sialic acid from an oligosaccharidic donor in the host, to parasite βGalp terminal units and it has been demonstrated that it plays an important role in the infection. 25670976 4 20 theme transfer 748:755 arg1 reaction 757:764 The transfer reaction 744:764 The transfer reaction of sialic acid 744:779 The transfer reaction of sialic acid was performed using a recombinant TcTS and 3'-sialyllactose as sialic acid donor, in the presence of the acceptor having βGalp non reducing ends. 25670976 2 21 theme parasite 516:523 arg1 units 540:544 parasite βGalp terminal units 516:544 parasite βGalp terminal units 516:544 This enzyme catalyzes the transfer of sialic acid from an oligosaccharidic donor in the host, to parasite βGalp terminal units and it has been demonstrated that it plays an important role in the infection. 25670976 2 22 theme acid 464:467 arg1 transfer 445:452 the transfer 441:452 the transfer of sialic acid from an oligosaccharidic donor in the host 441:510 This enzyme catalyzes the transfer of sialic acid from an oligosaccharidic donor in the host, to parasite βGalp terminal units and it has been demonstrated that it plays an important role in the infection. 25670976 9 23 gly sialylated 1541:1550 arg1 ligands 1552:1558 sialylated ligands 1541:1558 sialylated ligands 1541:1558 The usefulness of the enzymatic trans-sialylation for the preparation of sialylated ligands was assessed by performing a preparative sialylation of a divalent substrate, which afforded the monosialylated compound as main product, together with the disialylated glycocluster. 25670976 8 24 theme competitive 1374:1384 arg1 inhibitor 1386:1394 the strongest competitive inhibitor 1360:1394 the strongest competitive inhibitor among the compounds tested (70% inhibition at equimolar concentration) 1360:1465 A di-N-lactoside showed to be the strongest competitive inhibitor among the compounds tested (70% inhibition at equimolar concentration). 25670976 8 24 theme competitive 1374:1384 arg1 di-N-lactoside 1332:1345 A di-N-lactoside 1330:1345 A di-N-lactoside 1330:1345 A di-N-lactoside showed to be the strongest competitive inhibitor among the compounds tested (70% inhibition at equimolar concentration). 25670976 6 25 from 3'-sialyllactose 1163:1178 arg1 reaction 1149:1156 the sialic acid transfer reaction 1124:1156 the sialic acid transfer reaction from 3'-sialyllactose to the natural substrate N-acetyllactosamine 1124:1223 The ability of the different S-linked and N-linked glycosides to inhibit the sialic acid transfer reaction from 3'-sialyllactose to the natural substrate N-acetyllactosamine, was also studied. 25670976 9 26 theme preparative 1589:1599 arg1 sialylation 1601:1611 a preparative sialylation 1587:1611 a preparative sialylation of a divalent substrate, which afforded the monosialylated compound as main product, together with the disialylated glycocluster 1587:1740 The usefulness of the enzymatic trans-sialylation for the preparation of sialylated ligands was assessed by performing a preparative sialylation of a divalent substrate, which afforded the monosialylated compound as main product, together with the disialylated glycocluster. 25670976 0 27 theme divalent 13:20 arg1 ligands 22:28 divalent ligands 13:28 divalent ligands of β-thio- and β-N-galactopyranosides and related lactosides 13:89 Synthesis of divalent ligands of β-thio- and β-N-galactopyranosides and related lactosides and their evaluation as substrates and inhibitors of Trypanosoma cruzi trans-sialidase. 25670976 1 28 theme sugar 304:308 arg1 scaffolds 310:318 sugar scaffolds 304:318 sugar scaffolds 304:318 In this work we describe the synthesis of mono- and divalent β-N- and β-S-galactopyranosides and related lactosides built on sugar scaffolds and their evaluation as substrates and inhibitors of the Trypanosoma cruzi trans-sialidase (TcTS). 25670976 7 29 theme competitive 1306:1316 arg1 inhibitors 1318:1327 moderate competitive inhibitors 1297:1327 moderate competitive inhibitors 1297:1327 Most of the substrates behaved as good acceptors and moderate competitive inhibitors. 25670976 6 30 link N-linked 1093:1100 arg1 glycosides 1102:1111 the different S-linked and N-linked glycosides 1066:1111 the different S-linked and N-linked glycosides 1066:1111 The ability of the different S-linked and N-linked glycosides to inhibit the sialic acid transfer reaction from 3'-sialyllactose to the natural substrate N-acetyllactosamine, was also studied. 25670976 9 31 theme divalent 1618:1625 arg1 substrate 1627:1635 a divalent substrate 1616:1635 a divalent substrate 1616:1635 The usefulness of the enzymatic trans-sialylation for the preparation of sialylated ligands was assessed by performing a preparative sialylation of a divalent substrate, which afforded the monosialylated compound as main product, together with the disialylated glycocluster. 25670976 5 32 theme amperometric 1015:1026 arg1 HPAEC-PAD 1039:1047 HPAEC-PAD 1039:1047 HPAEC-PAD 1039:1047 The products were analyzed by high performance anion exchange chromatography with pulse amperometric detection (HPAEC-PAD). 25670976 5 32 theme amperometric 1015:1026 arg1 detection 1028:1036 pulse amperometric detection 1009:1036 pulse amperometric detection (HPAEC-PAD) 1009:1048 The products were analyzed by high performance anion exchange chromatography with pulse amperometric detection (HPAEC-PAD). 25670976 7 33 theme good 1278:1281 arg1 acceptors 1283:1291 good acceptors 1278:1291 good acceptors 1278:1291 Most of the substrates behaved as good acceptors and moderate competitive inhibitors. 25670976 9 34 gly sialylation 1601:1611 arg1 substrate 1627:1635 a divalent substrate 1616:1635 a divalent substrate 1616:1635 The usefulness of the enzymatic trans-sialylation for the preparation of sialylated ligands was assessed by performing a preparative sialylation of a divalent substrate, which afforded the monosialylated compound as main product, together with the disialylated glycocluster. 25670976 4 35 theme acid 776:779 arg1 reaction 757:764 The transfer reaction 744:764 The transfer reaction of sialic acid 744:779 The transfer reaction of sialic acid was performed using a recombinant TcTS and 3'-sialyllactose as sialic acid donor, in the presence of the acceptor having βGalp non reducing ends. 25670976 5 36 theme performance 962:972 arg1 chromatography 989:1002 high performance anion exchange chromatography 957:1002 high performance anion exchange chromatography with pulse amperometric detection (HPAEC-PAD) 957:1048 The products were analyzed by high performance anion exchange chromatography with pulse amperometric detection (HPAEC-PAD). 25670976 6 37 theme N-linked 1093:1100 arg1 glycosides 1102:1111 the different S-linked and N-linked glycosides 1066:1111 the different S-linked and N-linked glycosides 1066:1111 The ability of the different S-linked and N-linked glycosides to inhibit the sialic acid transfer reaction from 3'-sialyllactose to the natural substrate N-acetyllactosamine, was also studied. 25670976 6 38 link S-linked 1080:1087 arg1 glycosides 1102:1111 the different S-linked and N-linked glycosides 1066:1111 the different S-linked and N-linked glycosides 1066:1111 The ability of the different S-linked and N-linked glycosides to inhibit the sialic acid transfer reaction from 3'-sialyllactose to the natural substrate N-acetyllactosamine, was also studied. 25670976 1 39 theme β-N- 240:243 arg1 synthesis 208:216 the synthesis 204:216 the synthesis of mono- and divalent β-N- and β-S-galactopyranosides and related lactosides built on sugar scaffolds and their evaluation as substrates and inhibitors of the Trypanosoma cruzi trans-sialidase (TcTS) 204:416 In this work we describe the synthesis of mono- and divalent β-N- and β-S-galactopyranosides and related lactosides built on sugar scaffolds and their evaluation as substrates and inhibitors of the Trypanosoma cruzi trans-sialidase (TcTS). 25670976 9 40 theme monosialylated 1657:1670 arg1 compound 1672:1679 the monosialylated compound 1653:1679 the monosialylated compound as main product 1653:1695 The usefulness of the enzymatic trans-sialylation for the preparation of sialylated ligands was assessed by performing a preparative sialylation of a divalent substrate, which afforded the monosialylated compound as main product, together with the disialylated glycocluster. 25670976 6 41 theme S-linked 1080:1087 arg1 glycosides 1102:1111 the different S-linked and N-linked glycosides 1066:1111 the different S-linked and N-linked glycosides 1066:1111 The ability of the different S-linked and N-linked glycosides to inhibit the sialic acid transfer reaction from 3'-sialyllactose to the natural substrate N-acetyllactosamine, was also studied. 25670976 1 42 theme β-S-galactopyranosides 249:270 arg1 synthesis 208:216 the synthesis 204:216 the synthesis of mono- and divalent β-N- and β-S-galactopyranosides and related lactosides built on sugar scaffolds and their evaluation as substrates and inhibitors of the Trypanosoma cruzi trans-sialidase (TcTS) 204:416 In this work we describe the synthesis of mono- and divalent β-N- and β-S-galactopyranosides and related lactosides built on sugar scaffolds and their evaluation as substrates and inhibitors of the Trypanosoma cruzi trans-sialidase (TcTS). 25670976 2 43 theme important 592:600 arg1 role 602:605 an important role 589:605 an important role 589:605 This enzyme catalyzes the transfer of sialic acid from an oligosaccharidic donor in the host, to parasite βGalp terminal units and it has been demonstrated that it plays an important role in the infection. 25670976 5 44 theme pulse 1009:1013 arg1 HPAEC-PAD 1039:1047 HPAEC-PAD 1039:1047 HPAEC-PAD 1039:1047 The products were analyzed by high performance anion exchange chromatography with pulse amperometric detection (HPAEC-PAD). 25670976 5 44 theme pulse 1009:1013 arg1 detection 1028:1036 pulse amperometric detection 1009:1036 pulse amperometric detection (HPAEC-PAD) 1009:1048 The products were analyzed by high performance anion exchange chromatography with pulse amperometric detection (HPAEC-PAD). 25670976 1 45 theme related 276:282 arg1 lactosides 284:293 related lactosides 276:293 related lactosides 276:293 In this work we describe the synthesis of mono- and divalent β-N- and β-S-galactopyranosides and related lactosides built on sugar scaffolds and their evaluation as substrates and inhibitors of the Trypanosoma cruzi trans-sialidase (TcTS). 25670976 5 46 with chromatography 989:1002 arg1 HPAEC-PAD 1039:1047 HPAEC-PAD 1039:1047 HPAEC-PAD 1039:1047 The products were analyzed by high performance anion exchange chromatography with pulse amperometric detection (HPAEC-PAD). 25670976 5 46 with chromatography 989:1002 arg1 detection 1028:1036 pulse amperometric detection 1009:1036 pulse amperometric detection (HPAEC-PAD) 1009:1048 The products were analyzed by high performance anion exchange chromatography with pulse amperometric detection (HPAEC-PAD). 25670976 3 47 theme sialic 706:711 arg1 glycoclusters 729:741 sialic acid containing glycoclusters 706:741 sialic acid containing glycoclusters 706:741 Herein, the enzyme was also tested as a tool for the chemoenzymatic synthesis of sialic acid containing glycoclusters. 25670976 9 48 gly disialylated 1716:1727 arg1 glycocluster 1729:1740 the disialylated glycocluster 1712:1740 the disialylated glycocluster 1712:1740 The usefulness of the enzymatic trans-sialylation for the preparation of sialylated ligands was assessed by performing a preparative sialylation of a divalent substrate, which afforded the monosialylated compound as main product, together with the disialylated glycocluster. 25670976 6 49 theme acid 1135:1138 arg1 reaction 1149:1156 the sialic acid transfer reaction 1124:1156 the sialic acid transfer reaction from 3'-sialyllactose to the natural substrate N-acetyllactosamine 1124:1223 The ability of the different S-linked and N-linked glycosides to inhibit the sialic acid transfer reaction from 3'-sialyllactose to the natural substrate N-acetyllactosamine, was also studied. 25670976 4 50 theme acceptor 886:893 arg1 ends 921:924 the acceptor having βGalp non reducing ends 882:924 the acceptor having βGalp non reducing ends 882:924 The transfer reaction of sialic acid was performed using a recombinant TcTS and 3'-sialyllactose as sialic acid donor, in the presence of the acceptor having βGalp non reducing ends. 25670976 3 51 theme containing 718:727 arg1 glycoclusters 729:741 sialic acid containing glycoclusters 706:741 sialic acid containing glycoclusters 706:741 Herein, the enzyme was also tested as a tool for the chemoenzymatic synthesis of sialic acid containing glycoclusters. 25670976 0 52 theme Trypanosoma 144:154 arg1 trans-sialidase 162:176 Trypanosoma cruzi trans-sialidase 144:176 Trypanosoma cruzi trans-sialidase 144:176 Synthesis of divalent ligands of β-thio- and β-N-galactopyranosides and related lactosides and their evaluation as substrates and inhibitors of Trypanosoma cruzi trans-sialidase. 25670976 1 53 theme TcTS 412:415 arg1 scaffolds 310:318 sugar scaffolds 304:318 sugar scaffolds 304:318 In this work we describe the synthesis of mono- and divalent β-N- and β-S-galactopyranosides and related lactosides built on sugar scaffolds and their evaluation as substrates and inhibitors of the Trypanosoma cruzi trans-sialidase (TcTS). 25670976 1 53 theme TcTS 412:415 arg1 evaluation 330:339 their evaluation 324:339 their evaluation as substrates and inhibitors of the Trypanosoma cruzi trans-sialidase (TcTS) 324:416 In this work we describe the synthesis of mono- and divalent β-N- and β-S-galactopyranosides and related lactosides built on sugar scaffolds and their evaluation as substrates and inhibitors of the Trypanosoma cruzi trans-sialidase (TcTS). 25670976 4 54 theme βGalp 902:906 arg1 ends 921:924 the acceptor having βGalp non reducing ends 882:924 the acceptor having βGalp non reducing ends 882:924 The transfer reaction of sialic acid was performed using a recombinant TcTS and 3'-sialyllactose as sialic acid donor, in the presence of the acceptor having βGalp non reducing ends. 25670976 1 55 dep Trypanosoma 377:387 arg1 cruzi 389:393 cruzi 389:393 cruzi 389:393 In this work we describe the synthesis of mono- and divalent β-N- and β-S-galactopyranosides and related lactosides built on sugar scaffolds and their evaluation as substrates and inhibitors of the Trypanosoma cruzi trans-sialidase (TcTS). 25670976 4 56 theme ends 921:924 arg1 presence 870:877 the presence 866:877 the presence of the acceptor having βGalp non reducing ends 866:924 The transfer reaction of sialic acid was performed using a recombinant TcTS and 3'-sialyllactose as sialic acid donor, in the presence of the acceptor having βGalp non reducing ends. 25670976 0 57 theme trans-sialidase 162:176 arg1 inhibitors 130:139 inhibitors 130:139 inhibitors of Trypanosoma cruzi trans-sialidase 130:176 Synthesis of divalent ligands of β-thio- and β-N-galactopyranosides and related lactosides and their evaluation as substrates and inhibitors of Trypanosoma cruzi trans-sialidase. 25670976 0 57 theme trans-sialidase 162:176 arg1 substrates 115:124 substrates 115:124 substrates 115:124 Synthesis of divalent ligands of β-thio- and β-N-galactopyranosides and related lactosides and their evaluation as substrates and inhibitors of Trypanosoma cruzi trans-sialidase. 25670976 9 58 theme enzymatic 1490:1498 arg1 trans-sialylation 1500:1516 the enzymatic trans-sialylation 1486:1516 the enzymatic trans-sialylation 1486:1516 The usefulness of the enzymatic trans-sialylation for the preparation of sialylated ligands was assessed by performing a preparative sialylation of a divalent substrate, which afforded the monosialylated compound as main product, together with the disialylated glycocluster. 25670976 9 59 theme disialylated 1716:1727 arg1 glycocluster 1729:1740 the disialylated glycocluster 1712:1740 the disialylated glycocluster 1712:1740 The usefulness of the enzymatic trans-sialylation for the preparation of sialylated ligands was assessed by performing a preparative sialylation of a divalent substrate, which afforded the monosialylated compound as main product, together with the disialylated glycocluster. 25670976 8 60 dep % 1426:1426 arg1 inhibition 1428:1437 inhibition 1428:1437 70% inhibition 1424:1437 A di-N-lactoside showed to be the strongest competitive inhibitor among the compounds tested (70% inhibition at equimolar concentration). 25670976 6 61 theme substrate 1195:1203 arg1 N-acetyllactosamine 1205:1223 the natural substrate N-acetyllactosamine 1183:1223 the natural substrate N-acetyllactosamine 1183:1223 The ability of the different S-linked and N-linked glycosides to inhibit the sialic acid transfer reaction from 3'-sialyllactose to the natural substrate N-acetyllactosamine, was also studied. 25670976 0 62 theme related 72:78 arg1 lactosides 80:89 β-thio- and β-N-galactopyranosides and related lactosides 33:89 β-thio- and β-N-galactopyranosides and related lactosides 33:89 Synthesis of divalent ligands of β-thio- and β-N-galactopyranosides and related lactosides and their evaluation as substrates and inhibitors of Trypanosoma cruzi trans-sialidase. 25670976 4 63 theme reducing 912:919 arg1 ends 921:924 the acceptor having βGalp non reducing ends 882:924 the acceptor having βGalp non reducing ends 882:924 The transfer reaction of sialic acid was performed using a recombinant TcTS and 3'-sialyllactose as sialic acid donor, in the presence of the acceptor having βGalp non reducing ends. 25670976 8 64 from concentration 1452:1464 arg1 % 1426:1426 70% 1424:1426 70% inhibition 1424:1437 A di-N-lactoside showed to be the strongest competitive inhibitor among the compounds tested (70% inhibition at equimolar concentration). 25670976 9 65 theme sialylated 1541:1550 arg1 ligands 1552:1558 sialylated ligands 1541:1558 sialylated ligands 1541:1558 The usefulness of the enzymatic trans-sialylation for the preparation of sialylated ligands was assessed by performing a preparative sialylation of a divalent substrate, which afforded the monosialylated compound as main product, together with the disialylated glycocluster. 25670976 2 66 theme βGalp 525:529 arg1 units 540:544 parasite βGalp terminal units 516:544 parasite βGalp terminal units 516:544 This enzyme catalyzes the transfer of sialic acid from an oligosaccharidic donor in the host, to parasite βGalp terminal units and it has been demonstrated that it plays an important role in the infection. 25670976 1 67 theme Trypanosoma 377:387 arg1 TcTS 412:415 the Trypanosoma cruzi trans-sialidase (TcTS) 373:416 the Trypanosoma cruzi trans-sialidase (TcTS) 373:416 In this work we describe the synthesis of mono- and divalent β-N- and β-S-galactopyranosides and related lactosides built on sugar scaffolds and their evaluation as substrates and inhibitors of the Trypanosoma cruzi trans-sialidase (TcTS). 25670976 2 68 from donor 494:498 arg1 host 507:510 the host 503:510 the host 503:510 This enzyme catalyzes the transfer of sialic acid from an oligosaccharidic donor in the host, to parasite βGalp terminal units and it has been demonstrated that it plays an important role in the infection. 25670976 2 68 from donor 494:498 arg1 transfer 445:452 the transfer 441:452 the transfer of sialic acid from an oligosaccharidic donor in the host 441:510 This enzyme catalyzes the transfer of sialic acid from an oligosaccharidic donor in the host, to parasite βGalp terminal units and it has been demonstrated that it plays an important role in the infection. 25670976 1 69 theme trans-sialidase 395:409 arg1 TcTS 412:415 the Trypanosoma cruzi trans-sialidase (TcTS) 373:416 the Trypanosoma cruzi trans-sialidase (TcTS) 373:416 In this work we describe the synthesis of mono- and divalent β-N- and β-S-galactopyranosides and related lactosides built on sugar scaffolds and their evaluation as substrates and inhibitors of the Trypanosoma cruzi trans-sialidase (TcTS). 25670976 2 70 theme sialic 457:462 arg1 acid 464:467 sialic acid 457:467 sialic acid 457:467 This enzyme catalyzes the transfer of sialic acid from an oligosaccharidic donor in the host, to parasite βGalp terminal units and it has been demonstrated that it plays an important role in the infection. 25670976 8 71 theme strongest 1364:1372 arg1 inhibitor 1386:1394 the strongest competitive inhibitor 1360:1394 the strongest competitive inhibitor among the compounds tested (70% inhibition at equimolar concentration) 1360:1465 A di-N-lactoside showed to be the strongest competitive inhibitor among the compounds tested (70% inhibition at equimolar concentration). 25670976 8 71 theme strongest 1364:1372 arg1 di-N-lactoside 1332:1345 A di-N-lactoside 1330:1345 A di-N-lactoside 1330:1345 A di-N-lactoside showed to be the strongest competitive inhibitor among the compounds tested (70% inhibition at equimolar concentration). 25670976 0 72 theme ligands 22:28 arg1 evaluation 101:110 their evaluation 95:110 their evaluation as substrates and inhibitors of Trypanosoma cruzi trans-sialidase 95:176 Synthesis of divalent ligands of β-thio- and β-N-galactopyranosides and related lactosides and their evaluation as substrates and inhibitors of Trypanosoma cruzi trans-sialidase. 25670976 0 72 theme ligands 22:28 arg1 Synthesis 0:8 Synthesis 0:8 Synthesis of divalent ligands of β-thio- and β-N-galactopyranosides and related lactosides 0:89 Synthesis of divalent ligands of β-thio- and β-N-galactopyranosides and related lactosides and their evaluation as substrates and inhibitors of Trypanosoma cruzi trans-sialidase. 25670976 7 73 theme moderate 1297:1304 arg1 inhibitors 1318:1327 moderate competitive inhibitors 1297:1327 moderate competitive inhibitors 1297:1327 Most of the substrates behaved as good acceptors and moderate competitive inhibitors. 25670976 6 74 dep ability 1055:1061 arg1 inhibit 1116:1122 inhibit 1116:1122 to inhibit the sialic acid transfer reaction from 3'-sialyllactose to the natural substrate N-acetyllactosamine 1113:1223 The ability of the different S-linked and N-linked glycosides to inhibit the sialic acid transfer reaction from 3'-sialyllactose to the natural substrate N-acetyllactosamine, was also studied. 25670976 0 75 theme β-thio- 33:39 arg1 lactosides 80:89 β-thio- and β-N-galactopyranosides and related lactosides 33:89 β-thio- and β-N-galactopyranosides and related lactosides 33:89 Synthesis of divalent ligands of β-thio- and β-N-galactopyranosides and related lactosides and their evaluation as substrates and inhibitors of Trypanosoma cruzi trans-sialidase. 25670976 2 76 theme oligosaccharidic 477:492 arg1 donor 494:498 an oligosaccharidic donor 474:498 an oligosaccharidic donor in the host 474:510 This enzyme catalyzes the transfer of sialic acid from an oligosaccharidic donor in the host, to parasite βGalp terminal units and it has been demonstrated that it plays an important role in the infection. 25670976 0 77 theme β-N-galactopyranosides 45:66 arg1 lactosides 80:89 β-thio- and β-N-galactopyranosides and related lactosides 33:89 β-thio- and β-N-galactopyranosides and related lactosides 33:89 Synthesis of divalent ligands of β-thio- and β-N-galactopyranosides and related lactosides and their evaluation as substrates and inhibitors of Trypanosoma cruzi trans-sialidase. 25670976 9 78 theme substrate 1627:1635 arg1 sialylation 1601:1611 a preparative sialylation 1587:1611 a preparative sialylation of a divalent substrate, which afforded the monosialylated compound as main product, together with the disialylated glycocluster 1587:1740 The usefulness of the enzymatic trans-sialylation for the preparation of sialylated ligands was assessed by performing a preparative sialylation of a divalent substrate, which afforded the monosialylated compound as main product, together with the disialylated glycocluster. 25670976 4 79 theme recombinant 803:813 arg1 TcTS 815:818 a recombinant TcTS 801:818 a recombinant TcTS 801:818 The transfer reaction of sialic acid was performed using a recombinant TcTS and 3'-sialyllactose as sialic acid donor, in the presence of the acceptor having βGalp non reducing ends. 25670976 5 80 theme exchange 980:987 arg1 chromatography 989:1002 high performance anion exchange chromatography 957:1002 high performance anion exchange chromatography with pulse amperometric detection (HPAEC-PAD) 957:1048 The products were analyzed by high performance anion exchange chromatography with pulse amperometric detection (HPAEC-PAD). 25670976 5 81 theme high 957:960 arg1 chromatography 989:1002 high performance anion exchange chromatography 957:1002 high performance anion exchange chromatography with pulse amperometric detection (HPAEC-PAD) 957:1048 The products were analyzed by high performance anion exchange chromatography with pulse amperometric detection (HPAEC-PAD). 25670976 6 82 theme glycosides 1102:1111 arg1 ability 1055:1061 The ability 1051:1061 The ability 1051:1061 The ability of the different S-linked and N-linked glycosides to inhibit the sialic acid transfer reaction from 3'-sialyllactose to the natural substrate N-acetyllactosamine, was also studied. 25670976 4 83 theme sialic 769:774 arg1 acid 776:779 sialic acid 769:779 sialic acid 769:779 The transfer reaction of sialic acid was performed using a recombinant TcTS and 3'-sialyllactose as sialic acid donor, in the presence of the acceptor having βGalp non reducing ends. 25670976 1 84 theme divalent 231:238 arg1 β-N- 240:243 mono- and divalent β-N- 221:243 mono- and divalent β-N- 221:243 In this work we describe the synthesis of mono- and divalent β-N- and β-S-galactopyranosides and related lactosides built on sugar scaffolds and their evaluation as substrates and inhibitors of the Trypanosoma cruzi trans-sialidase (TcTS). 25670976 5 85 theme anion 974:978 arg1 chromatography 989:1002 high performance anion exchange chromatography 957:1002 high performance anion exchange chromatography with pulse amperometric detection (HPAEC-PAD) 957:1048 The products were analyzed by high performance anion exchange chromatography with pulse amperometric detection (HPAEC-PAD). 24751801 4 0 theme E. 846:847 arg1 mastitis 854:861 E. coli mastitis 846:861 E. coli mastitis 846:861 A total of 511 N-glycosylation sites, corresponding to 283 glycosylated proteins, were detected in the mammary tissues of cows with E. coli mastitis. 24751801 3 1 gly glycoproteins 613:625 arg1 glycoproteins 613:625 these glycoproteins 607:625 these glycoproteins 607:625 A total of 551 N-glycosylation sites, corresponding to 294 proteins, were identified in the mammary tissues of healthy cows; these glycoproteins were categorised into three functional groups and clustered into 11 specific pathways. 24751801 5 2 from cows 970:973 arg1 tissues 942:948 the mammary tissues 930:948 the mammary tissues of healthy cows 930:964 There were differences in N-glycosylation sites in 98 proteins in the mammary tissues of healthy cows and cows with mastitis due to E. coli. 24751801 7 3 gly glycoproteins 1364:1376 arg1 glycoproteins 1364:1376 altered glycoproteins 1356:1376 altered glycoproteins 1356:1376 The results from this study show that the glycosylated protein profile in the mammary tissues of healthy and mastitic cows are different, and altered glycoproteins are associated with several pathways, including the lysosome and O-glycan biosynthesis pathways. 24751801 7 4 theme altered 1356:1362 arg1 glycoproteins 1364:1376 altered glycoproteins 1356:1376 altered glycoproteins 1356:1376 The results from this study show that the glycosylated protein profile in the mammary tissues of healthy and mastitic cows are different, and altered glycoproteins are associated with several pathways, including the lysosome and O-glycan biosynthesis pathways. 24751801 6 5 theme altered 1024:1030 arg1 glycosylation 1032:1044 altered glycosylation 1024:1044 altered glycosylation 1024:1044 Most proteins with altered glycosylation were those involved in responses to stress, cell adhesion and the immune response, and were assigned to five specific pathways based on their gene ontology annotation. 24751801 3 6 theme specific 695:702 arg1 pathways 704:711 11 specific pathways 692:711 11 specific pathways 692:711 A total of 551 N-glycosylation sites, corresponding to 294 proteins, were identified in the mammary tissues of healthy cows; these glycoproteins were categorised into three functional groups and clustered into 11 specific pathways. 24751801 1 7 gly glycosylated 179:190 arg1 profile 200:206 the N-linked glycosylated protein profile 166:206 the N-linked glycosylated protein profile of mammary tissue from healthy cows and cows with mastitis due to Escherichia coli 166:289 The aim of this study was to investigate the N-linked glycosylated protein profile of mammary tissue from healthy cows and cows with mastitis due to Escherichia coli, in order to understand the molecular mechanisms of the host response to mastitis. 24751801 7 8 theme several 1398:1404 arg1 pathways 1406:1413 several pathways 1398:1413 several pathways 1398:1413 The results from this study show that the glycosylated protein profile in the mammary tissues of healthy and mastitic cows are different, and altered glycoproteins are associated with several pathways, including the lysosome and O-glycan biosynthesis pathways. 24751801 7 8 theme several 1398:1404 arg1 pathways 1465:1472 the lysosome and O-glycan biosynthesis pathways 1426:1472 pathways 1465:1472 The results from this study show that the glycosylated protein profile in the mammary tissues of healthy and mastitic cows are different, and altered glycoproteins are associated with several pathways, including the lysosome and O-glycan biosynthesis pathways. 24751801 7 8 theme several 1398:1404 arg1 lysosome 1430:1437 the lysosome and O-glycan biosynthesis pathways 1426:1472 lysosome 1430:1437 The results from this study show that the glycosylated protein profile in the mammary tissues of healthy and mastitic cows are different, and altered glycoproteins are associated with several pathways, including the lysosome and O-glycan biosynthesis pathways. 24751801 4 9 theme cows 836:839 arg1 tissues 825:831 the mammary tissues 813:831 the mammary tissues of cows with E. coli mastitis 813:861 A total of 511 N-glycosylation sites, corresponding to 283 glycosylated proteins, were detected in the mammary tissues of cows with E. coli mastitis. 24751801 6 10 theme immune 1112:1117 arg1 response 1119:1126 the immune response 1108:1126 the immune response 1108:1126 Most proteins with altered glycosylation were those involved in responses to stress, cell adhesion and the immune response, and were assigned to five specific pathways based on their gene ontology annotation. 24751801 6 11 theme gene 1188:1191 arg1 annotation 1202:1211 their gene ontology annotation 1182:1211 their gene ontology annotation 1182:1211 Most proteins with altered glycosylation were those involved in responses to stress, cell adhesion and the immune response, and were assigned to five specific pathways based on their gene ontology annotation. 24751801 1 12 theme N-linked 170:177 arg1 profile 200:206 the N-linked glycosylated protein profile 166:206 the N-linked glycosylated protein profile of mammary tissue from healthy cows and cows with mastitis due to Escherichia coli 166:289 The aim of this study was to investigate the N-linked glycosylated protein profile of mammary tissue from healthy cows and cows with mastitis due to Escherichia coli, in order to understand the molecular mechanisms of the host response to mastitis. 24751801 5 13 gly N-glycosylation 890:904 arg2 sites 906:910 N-glycosylation sites 890:910 N-glycosylation sites 890:910 There were differences in N-glycosylation sites in 98 proteins in the mammary tissues of healthy cows and cows with mastitis due to E. coli. 24751801 5 14 with proteins 918:925 arg1 mastitis 980:987 mastitis 980:987 mastitis due to E. coli 980:1002 There were differences in N-glycosylation sites in 98 proteins in the mammary tissues of healthy cows and cows with mastitis due to E. coli. 24751801 1 15 theme response 352:359 arg1 mechanisms 329:338 the molecular mechanisms 315:338 the molecular mechanisms of the host response to mastitis 315:371 The aim of this study was to investigate the N-linked glycosylated protein profile of mammary tissue from healthy cows and cows with mastitis due to Escherichia coli, in order to understand the molecular mechanisms of the host response to mastitis. 24751801 1 16 theme protein 192:198 arg1 profile 200:206 the N-linked glycosylated protein profile 166:206 the N-linked glycosylated protein profile of mammary tissue from healthy cows and cows with mastitis due to Escherichia coli 166:289 The aim of this study was to investigate the N-linked glycosylated protein profile of mammary tissue from healthy cows and cows with mastitis due to Escherichia coli, in order to understand the molecular mechanisms of the host response to mastitis. 24751801 7 17 theme mastitic 1323:1330 arg1 cows 1332:1335 healthy and mastitic cows 1311:1335 healthy and mastitic cows 1311:1335 The results from this study show that the glycosylated protein profile in the mammary tissues of healthy and mastitic cows are different, and altered glycoproteins are associated with several pathways, including the lysosome and O-glycan biosynthesis pathways. 24751801 1 18 from profile 200:206 arg1 cows 248:251 cows 248:251 cows with mastitis 248:265 The aim of this study was to investigate the N-linked glycosylated protein profile of mammary tissue from healthy cows and cows with mastitis due to Escherichia coli, in order to understand the molecular mechanisms of the host response to mastitis. 24751801 1 18 from profile 200:206 arg1 cows 239:242 healthy cows 231:242 healthy cows 231:242 The aim of this study was to investigate the N-linked glycosylated protein profile of mammary tissue from healthy cows and cows with mastitis due to Escherichia coli, in order to understand the molecular mechanisms of the host response to mastitis. 24751801 7 19 theme healthy 1311:1317 arg1 cows 1332:1335 healthy and mastitic cows 1311:1335 healthy and mastitic cows 1311:1335 The results from this study show that the glycosylated protein profile in the mammary tissues of healthy and mastitic cows are different, and altered glycoproteins are associated with several pathways, including the lysosome and O-glycan biosynthesis pathways. 24751801 5 20 theme N-glycosylation 890:904 arg1 sites 906:910 N-glycosylation sites 890:910 N-glycosylation sites 890:910 There were differences in N-glycosylation sites in 98 proteins in the mammary tissues of healthy cows and cows with mastitis due to E. coli. 24751801 0 21 from mastitis 105:112 arg1 cattle 117:122 cattle 117:122 cattle 117:122 Proteomics and pathway analysis of N-glycosylated mammary gland proteins in response to Escherichia coli mastitis in cattle. 24751801 6 22 theme specific 1155:1162 arg1 pathways 1164:1171 five specific pathways 1150:1171 five specific pathways based on their gene ontology annotation 1150:1211 Most proteins with altered glycosylation were those involved in responses to stress, cell adhesion and the immune response, and were assigned to five specific pathways based on their gene ontology annotation. 24751801 0 23 theme proteins 64:71 arg1 Proteomics 0:9 Proteomics 0:9 Proteomics 0:9 Proteomics and pathway analysis of N-glycosylated mammary gland proteins in response to Escherichia coli mastitis in cattle. 24751801 0 23 theme proteins 64:71 arg1 analysis 23:30 pathway analysis 15:30 pathway analysis 15:30 Proteomics and pathway analysis of N-glycosylated mammary gland proteins in response to Escherichia coli mastitis in cattle. 24751801 3 24 theme healthy 593:599 arg1 cows 601:604 healthy cows 593:604 healthy cows 593:604 A total of 551 N-glycosylation sites, corresponding to 294 proteins, were identified in the mammary tissues of healthy cows; these glycoproteins were categorised into three functional groups and clustered into 11 specific pathways. 24751801 4 25 with cows 836:839 arg1 mastitis 854:861 E. coli mastitis 846:861 E. coli mastitis 846:861 A total of 511 N-glycosylation sites, corresponding to 283 glycosylated proteins, were detected in the mammary tissues of cows with E. coli mastitis. 24751801 0 26 from Proteomics 0:9 arg1 response 76:83 response 76:83 response to Escherichia coli mastitis in cattle 76:122 Proteomics and pathway analysis of N-glycosylated mammary gland proteins in response to Escherichia coli mastitis in cattle. 24751801 2 27 gly N-glycopeptides 374:388 arg2 N-glycopeptides 374:388 N-glycopeptides 374:388 N-glycopeptides 374:388 N-glycopeptides were enriched with a lectin mixture and identified through high-accuracy mass spectrometry. 24751801 0 28 theme Escherichia 88:98 arg1 mastitis 105:112 Escherichia coli mastitis 88:112 Escherichia coli mastitis in cattle 88:122 Proteomics and pathway analysis of N-glycosylated mammary gland proteins in response to Escherichia coli mastitis in cattle. 24751801 4 29 gly N-glycosylation 729:743 arg2 sites 745:749 511 N-glycosylation sites 725:749 511 N-glycosylation sites 725:749 A total of 511 N-glycosylation sites, corresponding to 283 glycosylated proteins, were detected in the mammary tissues of cows with E. coli mastitis. 24751801 0 30 dep Escherichia 88:98 arg1 coli 100:103 coli 100:103 coli 100:103 Proteomics and pathway analysis of N-glycosylated mammary gland proteins in response to Escherichia coli mastitis in cattle. 24751801 7 31 gly glycosylated 1256:1267 arg1 profile 1277:1283 the glycosylated protein profile 1252:1283 the glycosylated protein profile in the mammary tissues of healthy and mastitic cows 1252:1335 The results from this study show that the glycosylated protein profile in the mammary tissues of healthy and mastitic cows are different, and altered glycoproteins are associated with several pathways, including the lysosome and O-glycan biosynthesis pathways. 24751801 7 31 gly glycosylated 1256:1267 arg1 different 1341:1349 different 1341:1349 different 1341:1349 The results from this study show that the glycosylated protein profile in the mammary tissues of healthy and mastitic cows are different, and altered glycoproteins are associated with several pathways, including the lysosome and O-glycan biosynthesis pathways. 24751801 7 32 theme protein 1269:1275 arg1 profile 1277:1283 the glycosylated protein profile 1252:1283 the glycosylated protein profile in the mammary tissues of healthy and mastitic cows 1252:1335 The results from this study show that the glycosylated protein profile in the mammary tissues of healthy and mastitic cows are different, and altered glycoproteins are associated with several pathways, including the lysosome and O-glycan biosynthesis pathways. 24751801 7 32 theme protein 1269:1275 arg1 different 1341:1349 different 1341:1349 different 1341:1349 The results from this study show that the glycosylated protein profile in the mammary tissues of healthy and mastitic cows are different, and altered glycoproteins are associated with several pathways, including the lysosome and O-glycan biosynthesis pathways. 24751801 2 33 theme lectin 411:416 arg1 mixture 418:424 a lectin mixture 409:424 a lectin mixture 409:424 N-glycopeptides were enriched with a lectin mixture and identified through high-accuracy mass spectrometry. 24751801 4 34 theme N-glycosylation 729:743 arg1 sites 745:749 511 N-glycosylation sites 725:749 511 N-glycosylation sites 725:749 A total of 511 N-glycosylation sites, corresponding to 283 glycosylated proteins, were detected in the mammary tissues of cows with E. coli mastitis. 24751801 0 35 theme pathway 15:21 arg1 analysis 23:30 pathway analysis 15:30 pathway analysis 15:30 Proteomics and pathway analysis of N-glycosylated mammary gland proteins in response to Escherichia coli mastitis in cattle. 24751801 6 36 theme Most 1005:1008 arg1 proteins 1010:1017 Most proteins 1005:1017 Most proteins with altered glycosylation 1005:1044 Most proteins with altered glycosylation were those involved in responses to stress, cell adhesion and the immune response, and were assigned to five specific pathways based on their gene ontology annotation. 24751801 2 37 theme mass 463:466 arg1 spectrometry 468:479 high-accuracy mass spectrometry 449:479 high-accuracy mass spectrometry 449:479 N-glycopeptides were enriched with a lectin mixture and identified through high-accuracy mass spectrometry. 24751801 4 38 gly glycosylated 773:784 arg1 proteins 786:793 283 glycosylated proteins 769:793 283 glycosylated proteins 769:793 A total of 511 N-glycosylation sites, corresponding to 283 glycosylated proteins, were detected in the mammary tissues of cows with E. coli mastitis. 24751801 1 39 with cows 248:251 arg1 mastitis 258:265 mastitis 258:265 mastitis 258:265 The aim of this study was to investigate the N-linked glycosylated protein profile of mammary tissue from healthy cows and cows with mastitis due to Escherichia coli, in order to understand the molecular mechanisms of the host response to mastitis. 24751801 6 40 gly glycosylation 1032:1044 arg1 proteins 1010:1017 Most proteins 1005:1017 Most proteins with altered glycosylation 1005:1044 Most proteins with altered glycosylation were those involved in responses to stress, cell adhesion and the immune response, and were assigned to five specific pathways based on their gene ontology annotation. 24751801 0 41 theme mammary 50:56 arg1 proteins 64:71 N-glycosylated mammary gland proteins 35:71 N-glycosylated mammary gland proteins 35:71 Proteomics and pathway analysis of N-glycosylated mammary gland proteins in response to Escherichia coli mastitis in cattle. 24751801 1 42 with cows 239:242 arg1 mastitis 258:265 mastitis 258:265 mastitis 258:265 The aim of this study was to investigate the N-linked glycosylated protein profile of mammary tissue from healthy cows and cows with mastitis due to Escherichia coli, in order to understand the molecular mechanisms of the host response to mastitis. 24751801 4 43 theme glycosylated 773:784 arg1 proteins 786:793 283 glycosylated proteins 769:793 283 glycosylated proteins 769:793 A total of 511 N-glycosylation sites, corresponding to 283 glycosylated proteins, were detected in the mammary tissues of cows with E. coli mastitis. 24751801 1 44 theme mammary 211:217 arg1 tissue 219:224 mammary tissue 211:224 mammary tissue from healthy cows and cows with mastitis 211:265 The aim of this study was to investigate the N-linked glycosylated protein profile of mammary tissue from healthy cows and cows with mastitis due to Escherichia coli, in order to understand the molecular mechanisms of the host response to mastitis. 24751801 7 45 theme O-glycan 1443:1450 arg1 pathways 1465:1472 the lysosome and O-glycan biosynthesis pathways 1426:1472 pathways 1465:1472 The results from this study show that the glycosylated protein profile in the mammary tissues of healthy and mastitic cows are different, and altered glycoproteins are associated with several pathways, including the lysosome and O-glycan biosynthesis pathways. 24751801 7 46 from study 1236:1240 arg1 results 1218:1224 The results 1214:1224 The results from this study 1214:1240 The results from this study show that the glycosylated protein profile in the mammary tissues of healthy and mastitic cows are different, and altered glycoproteins are associated with several pathways, including the lysosome and O-glycan biosynthesis pathways. 24751801 4 47 located detected 801:808 arg2 total 716:720 A total 714:720 A total 714:720 A total of 511 N-glycosylation sites, corresponding to 283 glycosylated proteins, were detected in the mammary tissues of cows with E. coli mastitis. 24751801 4 47 located detected 801:808 arg1 tissues 825:831 the mammary tissues 813:831 the mammary tissues of cows with E. coli mastitis 813:861 A total of 511 N-glycosylation sites, corresponding to 283 glycosylated proteins, were detected in the mammary tissues of cows with E. coli mastitis. 24751801 5 48 with cows 970:973 arg1 mastitis 980:987 mastitis 980:987 mastitis due to E. coli 980:1002 There were differences in N-glycosylation sites in 98 proteins in the mammary tissues of healthy cows and cows with mastitis due to E. coli. 24751801 3 49 theme N-glycosylation 497:511 arg1 sites 513:517 551 N-glycosylation sites 493:517 551 N-glycosylation sites 493:517 A total of 551 N-glycosylation sites, corresponding to 294 proteins, were identified in the mammary tissues of healthy cows; these glycoproteins were categorised into three functional groups and clustered into 11 specific pathways. 24751801 5 50 from proteins 918:925 arg1 tissues 942:948 the mammary tissues 930:948 the mammary tissues of healthy cows 930:964 There were differences in N-glycosylation sites in 98 proteins in the mammary tissues of healthy cows and cows with mastitis due to E. coli. 24751801 4 51 dep E. 846:847 arg1 coli 849:852 coli 849:852 coli 849:852 A total of 511 N-glycosylation sites, corresponding to 283 glycosylated proteins, were detected in the mammary tissues of cows with E. coli mastitis. 24751801 7 52 from profile 1277:1283 arg1 tissues 1300:1306 the mammary tissues 1288:1306 the mammary tissues of healthy and mastitic cows 1288:1335 The results from this study show that the glycosylated protein profile in the mammary tissues of healthy and mastitic cows are different, and altered glycoproteins are associated with several pathways, including the lysosome and O-glycan biosynthesis pathways. 24751801 4 53 theme mammary 817:823 arg1 tissues 825:831 the mammary tissues 813:831 the mammary tissues of cows with E. coli mastitis 813:861 A total of 511 N-glycosylation sites, corresponding to 283 glycosylated proteins, were detected in the mammary tissues of cows with E. coli mastitis. 24751801 6 54 theme ontology 1193:1200 arg1 annotation 1202:1211 their gene ontology annotation 1182:1211 their gene ontology annotation 1182:1211 Most proteins with altered glycosylation were those involved in responses to stress, cell adhesion and the immune response, and were assigned to five specific pathways based on their gene ontology annotation. 24751801 0 55 gly N-glycosylated 35:48 arg1 proteins 64:71 N-glycosylated mammary gland proteins 35:71 N-glycosylated mammary gland proteins 35:71 Proteomics and pathway analysis of N-glycosylated mammary gland proteins in response to Escherichia coli mastitis in cattle. 24751801 1 56 from cows 248:251 arg1 profile 200:206 the N-linked glycosylated protein profile 166:206 the N-linked glycosylated protein profile of mammary tissue from healthy cows and cows with mastitis due to Escherichia coli 166:289 The aim of this study was to investigate the N-linked glycosylated protein profile of mammary tissue from healthy cows and cows with mastitis due to Escherichia coli, in order to understand the molecular mechanisms of the host response to mastitis. 24751801 1 56 from cows 248:251 arg1 tissue 219:224 mammary tissue 211:224 mammary tissue from healthy cows and cows with mastitis 211:265 The aim of this study was to investigate the N-linked glycosylated protein profile of mammary tissue from healthy cows and cows with mastitis due to Escherichia coli, in order to understand the molecular mechanisms of the host response to mastitis. 24751801 1 57 theme glycosylated 179:190 arg1 profile 200:206 the N-linked glycosylated protein profile 166:206 the N-linked glycosylated protein profile of mammary tissue from healthy cows and cows with mastitis due to Escherichia coli 166:289 The aim of this study was to investigate the N-linked glycosylated protein profile of mammary tissue from healthy cows and cows with mastitis due to Escherichia coli, in order to understand the molecular mechanisms of the host response to mastitis. 24751801 1 58 from cows 239:242 arg1 profile 200:206 the N-linked glycosylated protein profile 166:206 the N-linked glycosylated protein profile of mammary tissue from healthy cows and cows with mastitis due to Escherichia coli 166:289 The aim of this study was to investigate the N-linked glycosylated protein profile of mammary tissue from healthy cows and cows with mastitis due to Escherichia coli, in order to understand the molecular mechanisms of the host response to mastitis. 24751801 1 58 from cows 239:242 arg1 tissue 219:224 mammary tissue 211:224 mammary tissue from healthy cows and cows with mastitis 211:265 The aim of this study was to investigate the N-linked glycosylated protein profile of mammary tissue from healthy cows and cows with mastitis due to Escherichia coli, in order to understand the molecular mechanisms of the host response to mastitis. 24751801 3 59 theme mammary 574:580 arg1 tissues 582:588 the mammary tissues 570:588 the mammary tissues of healthy cows 570:604 A total of 551 N-glycosylation sites, corresponding to 294 proteins, were identified in the mammary tissues of healthy cows; these glycoproteins were categorised into three functional groups and clustered into 11 specific pathways. 24751801 7 60 theme cows 1332:1335 arg1 tissues 1300:1306 the mammary tissues 1288:1306 the mammary tissues of healthy and mastitic cows 1288:1335 The results from this study show that the glycosylated protein profile in the mammary tissues of healthy and mastitic cows are different, and altered glycoproteins are associated with several pathways, including the lysosome and O-glycan biosynthesis pathways. 24751801 3 61 theme cows 601:604 arg1 tissues 582:588 the mammary tissues 570:588 the mammary tissues of healthy cows 570:604 A total of 551 N-glycosylation sites, corresponding to 294 proteins, were identified in the mammary tissues of healthy cows; these glycoproteins were categorised into three functional groups and clustered into 11 specific pathways. 24751801 0 62 from analysis 23:30 arg1 response 76:83 response 76:83 response to Escherichia coli mastitis in cattle 76:122 Proteomics and pathway analysis of N-glycosylated mammary gland proteins in response to Escherichia coli mastitis in cattle. 24751801 7 63 theme mammary 1292:1298 arg1 tissues 1300:1306 the mammary tissues 1288:1306 the mammary tissues of healthy and mastitic cows 1288:1335 The results from this study show that the glycosylated protein profile in the mammary tissues of healthy and mastitic cows are different, and altered glycoproteins are associated with several pathways, including the lysosome and O-glycan biosynthesis pathways. 24751801 1 64 theme study 141:145 arg1 aim 129:131 The aim 125:131 The aim of this study 125:145 The aim of this study was to investigate the N-linked glycosylated protein profile of mammary tissue from healthy cows and cows with mastitis due to Escherichia coli, in order to understand the molecular mechanisms of the host response to mastitis. 24751801 6 65 with proteins 1010:1017 arg1 glycosylation 1032:1044 altered glycosylation 1024:1044 altered glycosylation 1024:1044 Most proteins with altered glycosylation were those involved in responses to stress, cell adhesion and the immune response, and were assigned to five specific pathways based on their gene ontology annotation. 24751801 1 66 theme molecular 319:327 arg1 mechanisms 329:338 the molecular mechanisms 315:338 the molecular mechanisms of the host response to mastitis 315:371 The aim of this study was to investigate the N-linked glycosylated protein profile of mammary tissue from healthy cows and cows with mastitis due to Escherichia coli, in order to understand the molecular mechanisms of the host response to mastitis. 24751801 5 67 from differences 875:885 arg1 cows 970:973 cows 970:973 cows with mastitis due to E. coli 970:1002 There were differences in N-glycosylation sites in 98 proteins in the mammary tissues of healthy cows and cows with mastitis due to E. coli. 24751801 5 67 from differences 875:885 arg1 sites 906:910 N-glycosylation sites 890:910 N-glycosylation sites 890:910 There were differences in N-glycosylation sites in 98 proteins in the mammary tissues of healthy cows and cows with mastitis due to E. coli. 24751801 5 67 from differences 875:885 arg1 proteins 918:925 98 proteins 915:925 98 proteins in the mammary tissues of healthy cows 915:964 There were differences in N-glycosylation sites in 98 proteins in the mammary tissues of healthy cows and cows with mastitis due to E. coli. 24751801 5 68 theme mammary 934:940 arg1 tissues 942:948 the mammary tissues 930:948 the mammary tissues of healthy cows 930:964 There were differences in N-glycosylation sites in 98 proteins in the mammary tissues of healthy cows and cows with mastitis due to E. coli. 24751801 4 69 theme sites 745:749 arg1 total 716:720 A total 714:720 A total 714:720 A total of 511 N-glycosylation sites, corresponding to 283 glycosylated proteins, were detected in the mammary tissues of cows with E. coli mastitis. 24751801 3 70 gly N-glycosylation 497:511 arg2 sites 513:517 551 N-glycosylation sites 493:517 551 N-glycosylation sites 493:517 A total of 551 N-glycosylation sites, corresponding to 294 proteins, were identified in the mammary tissues of healthy cows; these glycoproteins were categorised into three functional groups and clustered into 11 specific pathways. 24751801 3 70 gly N-glycosylation 497:511 arg2 551 493:495 551 493:495 551 493:495 A total of 551 N-glycosylation sites, corresponding to 294 proteins, were identified in the mammary tissues of healthy cows; these glycoproteins were categorised into three functional groups and clustered into 11 specific pathways. 24751801 1 71 link N-linked 170:177 arg1 profile 200:206 the N-linked glycosylated protein profile 166:206 the N-linked glycosylated protein profile of mammary tissue from healthy cows and cows with mastitis due to Escherichia coli 166:289 The aim of this study was to investigate the N-linked glycosylated protein profile of mammary tissue from healthy cows and cows with mastitis due to Escherichia coli, in order to understand the molecular mechanisms of the host response to mastitis. 24751801 1 72 theme host 347:350 arg1 response 352:359 the host response 343:359 the host response to mastitis 343:371 The aim of this study was to investigate the N-linked glycosylated protein profile of mammary tissue from healthy cows and cows with mastitis due to Escherichia coli, in order to understand the molecular mechanisms of the host response to mastitis. 24751801 7 73 theme glycosylated 1256:1267 arg1 profile 1277:1283 the glycosylated protein profile 1252:1283 the glycosylated protein profile in the mammary tissues of healthy and mastitic cows 1252:1335 The results from this study show that the glycosylated protein profile in the mammary tissues of healthy and mastitic cows are different, and altered glycoproteins are associated with several pathways, including the lysosome and O-glycan biosynthesis pathways. 24751801 7 73 theme glycosylated 1256:1267 arg1 different 1341:1349 different 1341:1349 different 1341:1349 The results from this study show that the glycosylated protein profile in the mammary tissues of healthy and mastitic cows are different, and altered glycoproteins are associated with several pathways, including the lysosome and O-glycan biosynthesis pathways. 24751801 4 74 theme 511 725:727 arg1 sites 745:749 511 N-glycosylation sites 725:749 511 N-glycosylation sites 725:749 A total of 511 N-glycosylation sites, corresponding to 283 glycosylated proteins, were detected in the mammary tissues of cows with E. coli mastitis. 24751801 0 75 theme N-glycosylated 35:48 arg1 proteins 64:71 N-glycosylated mammary gland proteins 35:71 N-glycosylated mammary gland proteins 35:71 Proteomics and pathway analysis of N-glycosylated mammary gland proteins in response to Escherichia coli mastitis in cattle. 24751801 2 76 theme high-accuracy 449:461 arg1 spectrometry 468:479 high-accuracy mass spectrometry 449:479 high-accuracy mass spectrometry 449:479 N-glycopeptides were enriched with a lectin mixture and identified through high-accuracy mass spectrometry. 24751801 0 77 theme gland 58:62 arg1 proteins 64:71 N-glycosylated mammary gland proteins 35:71 N-glycosylated mammary gland proteins 35:71 Proteomics and pathway analysis of N-glycosylated mammary gland proteins in response to Escherichia coli mastitis in cattle. 24751801 6 78 theme cell 1090:1093 arg1 adhesion 1095:1102 cell adhesion 1090:1102 cell adhesion 1090:1102 Most proteins with altered glycosylation were those involved in responses to stress, cell adhesion and the immune response, and were assigned to five specific pathways based on their gene ontology annotation. 24751801 3 79 theme functional 655:664 arg1 groups 666:671 three functional groups 649:671 three functional groups 649:671 A total of 551 N-glycosylation sites, corresponding to 294 proteins, were identified in the mammary tissues of healthy cows; these glycoproteins were categorised into three functional groups and clustered into 11 specific pathways. 24751801 5 80 theme cows 961:964 arg1 tissues 942:948 the mammary tissues 930:948 the mammary tissues of healthy cows 930:964 There were differences in N-glycosylation sites in 98 proteins in the mammary tissues of healthy cows and cows with mastitis due to E. coli. 24751801 5 81 theme healthy 953:959 arg1 cows 961:964 healthy cows 953:964 healthy cows 953:964 There were differences in N-glycosylation sites in 98 proteins in the mammary tissues of healthy cows and cows with mastitis due to E. coli. 24751801 1 82 theme tissue 219:224 arg1 profile 200:206 the N-linked glycosylated protein profile 166:206 the N-linked glycosylated protein profile of mammary tissue from healthy cows and cows with mastitis due to Escherichia coli 166:289 The aim of this study was to investigate the N-linked glycosylated protein profile of mammary tissue from healthy cows and cows with mastitis due to Escherichia coli, in order to understand the molecular mechanisms of the host response to mastitis. 24751801 7 83 theme biosynthesis 1452:1463 arg1 pathways 1465:1472 the lysosome and O-glycan biosynthesis pathways 1426:1472 pathways 1465:1472 The results from this study show that the glycosylated protein profile in the mammary tissues of healthy and mastitic cows are different, and altered glycoproteins are associated with several pathways, including the lysosome and O-glycan biosynthesis pathways. 24751801 3 84 theme sites 513:517 arg1 total 484:488 A total 482:488 A total 482:488 A total of 551 N-glycosylation sites, corresponding to 294 proteins, were identified in the mammary tissues of healthy cows; these glycoproteins were categorised into three functional groups and clustered into 11 specific pathways. 24751801 1 85 theme healthy 231:237 arg1 cows 239:242 healthy cows 231:242 healthy cows 231:242 The aim of this study was to investigate the N-linked glycosylated protein profile of mammary tissue from healthy cows and cows with mastitis due to Escherichia coli, in order to understand the molecular mechanisms of the host response to mastitis. 25881000 0 0 theme rAAV1 106:110 arg1 Vectors 112:118 rAAV1 Vectors 106:118 rAAV1 Vectors 106:118 Serotype-specific Binding Properties and Nanoparticle Characteristics Contribute to the Immunogenicity of rAAV1 Vectors. 25881000 6 1 theme rAAV1 1290:1294 arg1 properties 1276:1285 serotype-specific cell-targeting properties 1243:1285 serotype-specific cell-targeting properties of rAAV1 1243:1294 Therefore, combinations of structural and of serotype-specific cell-targeting properties of rAAV1 determine its complex immunogenicity. 25881000 1 2 theme rAAV 187:190 arg1 vectors 207:213 recombinant adeno-associated virus (rAAV) gene transfer vectors 151:213 recombinant adeno-associated virus (rAAV) gene transfer vectors 151:213 The immunogenic properties of recombinant adeno-associated virus (rAAV) gene transfer vectors remain incompletely characterized in spite of their usage as gene therapy vectors or as vaccines. 25881000 2 3 from interactions 323:334 arg1 transgene 450:458 transgene 450:458 transgene 450:458 Molecular interactions between rAAV and various types of antigen-presenting cells (APCs), as well as the impact of these interactions on transgene or capsid-specific immunization remain unclear. 25881000 2 3 from interactions 323:334 arg1 immunization 479:490 capsid-specific immunization 463:490 capsid-specific immunization 463:490 Molecular interactions between rAAV and various types of antigen-presenting cells (APCs), as well as the impact of these interactions on transgene or capsid-specific immunization remain unclear. 25881000 1 4 theme gene 276:279 arg1 vectors 289:295 gene therapy vectors 276:295 gene therapy vectors 276:295 The immunogenic properties of recombinant adeno-associated virus (rAAV) gene transfer vectors remain incompletely characterized in spite of their usage as gene therapy vectors or as vaccines. 25881000 4 5 dep capsid 985:990 arg1 the 981:983 the 981:983 the 981:983 Using rAAV capsid serotype 1 (rAAV1) vectors which primary receptors on target cells are α2,3 and α2,6 N-linked sialic acids, we show that sialic acid-dependent binding of rAAV1 on APCs is essential to trigger CD4(+) T-cell responses by increasing rAAV1 uptake and contributing to antigenic presentation of both the capsid and transgene product although this involves different APCs. 25881000 2 6 theme cells 389:393 arg1 rAAV 344:347 rAAV 344:347 rAAV 344:347 Molecular interactions between rAAV and various types of antigen-presenting cells (APCs), as well as the impact of these interactions on transgene or capsid-specific immunization remain unclear. 25881000 2 6 theme cells 389:393 arg1 types 361:365 various types 353:365 various types of antigen-presenting cells (APCs) 353:400 Molecular interactions between rAAV and various types of antigen-presenting cells (APCs), as well as the impact of these interactions on transgene or capsid-specific immunization remain unclear. 25881000 1 7 theme therapy 281:287 arg1 vectors 289:295 gene therapy vectors 276:295 gene therapy vectors 276:295 The immunogenic properties of recombinant adeno-associated virus (rAAV) gene transfer vectors remain incompletely characterized in spite of their usage as gene therapy vectors or as vaccines. 25881000 7 8 theme vaccination 1478:1488 arg1 applications 1490:1501 vaccination applications 1478:1501 vaccination applications 1478:1501 These findings may be useful to guide a selection of rAAV variants depending on the intended level of immunogenicity for either gene therapy or vaccination applications. 25881000 6 9 theme properties 1276:1285 arg1 combinations 1209:1220 combinations 1209:1220 combinations of structural and of serotype-specific cell-targeting properties of rAAV1 1209:1294 Therefore, combinations of structural and of serotype-specific cell-targeting properties of rAAV1 determine its complex immunogenicity. 25881000 2 10 theme Molecular 313:321 arg1 interactions 323:334 Molecular interactions 313:334 Molecular interactions between rAAV and various types of antigen-presenting cells (APCs) 313:400 Molecular interactions between rAAV and various types of antigen-presenting cells (APCs), as well as the impact of these interactions on transgene or capsid-specific immunization remain unclear. 25881000 4 11 theme capsid 680:685 arg1 vectors 706:712 rAAV capsid serotype 1 (rAAV1) vectors 675:712 rAAV capsid serotype 1 (rAAV1) vectors which primary receptors on target cells are α2,3 and α2,6 N-linked sialic acids 675:792 Using rAAV capsid serotype 1 (rAAV1) vectors which primary receptors on target cells are α2,3 and α2,6 N-linked sialic acids, we show that sialic acid-dependent binding of rAAV1 on APCs is essential to trigger CD4(+) T-cell responses by increasing rAAV1 uptake and contributing to antigenic presentation of both the capsid and transgene product although this involves different APCs. 25881000 5 12 theme APCs 1192:1195 arg1 mobilization 1156:1167 mobilization 1156:1167 mobilization 1156:1167 In addition, the nanoparticulate structure of the vector in itself appears to be sufficient to trigger mobilization and activation of some APCs. 25881000 5 12 theme APCs 1192:1195 arg1 activation 1173:1182 activation 1173:1182 activation of some APCs 1173:1195 In addition, the nanoparticulate structure of the vector in itself appears to be sufficient to trigger mobilization and activation of some APCs. 25881000 0 13 theme Vectors 112:118 arg1 Immunogenicity 88:101 the Immunogenicity 84:101 the Immunogenicity of rAAV1 Vectors 84:118 Serotype-specific Binding Properties and Nanoparticle Characteristics Contribute to the Immunogenicity of rAAV1 Vectors. 25881000 5 14 theme nanoparticulate 1070:1084 arg1 sufficient 1134:1143 sufficient 1134:1143 sufficient 1134:1143 In addition, the nanoparticulate structure of the vector in itself appears to be sufficient to trigger mobilization and activation of some APCs. 25881000 5 14 theme nanoparticulate 1070:1084 arg1 structure 1086:1094 the nanoparticulate structure 1066:1094 the nanoparticulate structure of the vector in itself 1066:1118 In addition, the nanoparticulate structure of the vector in itself appears to be sufficient to trigger mobilization and activation of some APCs. 25881000 6 15 theme cell-targeting 1261:1274 arg1 properties 1276:1285 serotype-specific cell-targeting properties 1243:1285 serotype-specific cell-targeting properties of rAAV1 1243:1294 Therefore, combinations of structural and of serotype-specific cell-targeting properties of rAAV1 determine its complex immunogenicity. 25881000 7 16 theme immunogenicity 1436:1449 arg1 level 1427:1431 the intended level 1414:1431 the intended level of immunogenicity for either gene therapy or vaccination applications 1414:1501 These findings may be useful to guide a selection of rAAV variants depending on the intended level of immunogenicity for either gene therapy or vaccination applications. 25881000 1 17 theme adeno-associated 163:178 arg1 vectors 207:213 recombinant adeno-associated virus (rAAV) gene transfer vectors 151:213 recombinant adeno-associated virus (rAAV) gene transfer vectors 151:213 The immunogenic properties of recombinant adeno-associated virus (rAAV) gene transfer vectors remain incompletely characterized in spite of their usage as gene therapy vectors or as vaccines. 25881000 4 18 theme primary 720:726 arg1 acids 788:792 α2,3 and α2,6 N-linked sialic acids 758:792 α2,3 and α2,6 N-linked sialic acids 758:792 Using rAAV capsid serotype 1 (rAAV1) vectors which primary receptors on target cells are α2,3 and α2,6 N-linked sialic acids, we show that sialic acid-dependent binding of rAAV1 on APCs is essential to trigger CD4(+) T-cell responses by increasing rAAV1 uptake and contributing to antigenic presentation of both the capsid and transgene product although this involves different APCs. 25881000 4 18 theme primary 720:726 arg1 receptors 728:736 primary receptors 720:736 primary receptors on target cells 720:752 Using rAAV capsid serotype 1 (rAAV1) vectors which primary receptors on target cells are α2,3 and α2,6 N-linked sialic acids, we show that sialic acid-dependent binding of rAAV1 on APCs is essential to trigger CD4(+) T-cell responses by increasing rAAV1 uptake and contributing to antigenic presentation of both the capsid and transgene product although this involves different APCs. 25881000 4 19 theme rAAV1 841:845 arg1 binding 830:836 sialic acid-dependent binding 808:836 sialic acid-dependent binding of rAAV1 on APCs 808:853 Using rAAV capsid serotype 1 (rAAV1) vectors which primary receptors on target cells are α2,3 and α2,6 N-linked sialic acids, we show that sialic acid-dependent binding of rAAV1 on APCs is essential to trigger CD4(+) T-cell responses by increasing rAAV1 uptake and contributing to antigenic presentation of both the capsid and transgene product although this involves different APCs. 25881000 4 20 theme sialic 781:786 arg1 acids 788:792 α2,3 and α2,6 N-linked sialic acids 758:792 α2,3 and α2,6 N-linked sialic acids 758:792 Using rAAV capsid serotype 1 (rAAV1) vectors which primary receptors on target cells are α2,3 and α2,6 N-linked sialic acids, we show that sialic acid-dependent binding of rAAV1 on APCs is essential to trigger CD4(+) T-cell responses by increasing rAAV1 uptake and contributing to antigenic presentation of both the capsid and transgene product although this involves different APCs. 25881000 4 20 theme sialic 781:786 arg1 receptors 728:736 primary receptors 720:736 primary receptors on target cells 720:752 Using rAAV capsid serotype 1 (rAAV1) vectors which primary receptors on target cells are α2,3 and α2,6 N-linked sialic acids, we show that sialic acid-dependent binding of rAAV1 on APCs is essential to trigger CD4(+) T-cell responses by increasing rAAV1 uptake and contributing to antigenic presentation of both the capsid and transgene product although this involves different APCs. 25881000 1 21 theme gene 193:196 arg1 vectors 207:213 recombinant adeno-associated virus (rAAV) gene transfer vectors 151:213 recombinant adeno-associated virus (rAAV) gene transfer vectors 151:213 The immunogenic properties of recombinant adeno-associated virus (rAAV) gene transfer vectors remain incompletely characterized in spite of their usage as gene therapy vectors or as vaccines. 25881000 4 22 theme capsid 985:990 arg1 presentation 960:971 antigenic presentation 950:971 antigenic presentation of both the capsid and transgene product 950:1012 Using rAAV capsid serotype 1 (rAAV1) vectors which primary receptors on target cells are α2,3 and α2,6 N-linked sialic acids, we show that sialic acid-dependent binding of rAAV1 on APCs is essential to trigger CD4(+) T-cell responses by increasing rAAV1 uptake and contributing to antigenic presentation of both the capsid and transgene product although this involves different APCs. 25881000 4 23 theme transgene 996:1004 arg1 product 1006:1012 transgene product 996:1012 transgene product 996:1012 Using rAAV capsid serotype 1 (rAAV1) vectors which primary receptors on target cells are α2,3 and α2,6 N-linked sialic acids, we show that sialic acid-dependent binding of rAAV1 on APCs is essential to trigger CD4(+) T-cell responses by increasing rAAV1 uptake and contributing to antigenic presentation of both the capsid and transgene product although this involves different APCs. 25881000 1 24 theme transfer 198:205 arg1 vectors 207:213 recombinant adeno-associated virus (rAAV) gene transfer vectors 151:213 recombinant adeno-associated virus (rAAV) gene transfer vectors 151:213 The immunogenic properties of recombinant adeno-associated virus (rAAV) gene transfer vectors remain incompletely characterized in spite of their usage as gene therapy vectors or as vaccines. 25881000 0 25 theme Binding 18:24 arg1 Properties 26:35 Serotype-specific Binding Properties 0:35 Serotype-specific Binding Properties 0:35 Serotype-specific Binding Properties and Nanoparticle Characteristics Contribute to the Immunogenicity of rAAV1 Vectors. 25881000 6 26 theme complex 1310:1316 arg1 immunogenicity 1318:1331 its complex immunogenicity 1306:1331 its complex immunogenicity 1306:1331 Therefore, combinations of structural and of serotype-specific cell-targeting properties of rAAV1 determine its complex immunogenicity. 25881000 1 27 theme vectors 207:213 arg1 properties 137:146 The immunogenic properties 121:146 The immunogenic properties of recombinant adeno-associated virus (rAAV) gene transfer vectors 121:213 The immunogenic properties of recombinant adeno-associated virus (rAAV) gene transfer vectors remain incompletely characterized in spite of their usage as gene therapy vectors or as vaccines. 25881000 0 28 theme Serotype-specific 0:16 arg1 Properties 26:35 Serotype-specific Binding Properties 0:35 Serotype-specific Binding Properties 0:35 Serotype-specific Binding Properties and Nanoparticle Characteristics Contribute to the Immunogenicity of rAAV1 Vectors. 25881000 6 29 theme serotype-specific 1243:1259 arg1 properties 1276:1285 serotype-specific cell-targeting properties 1243:1285 serotype-specific cell-targeting properties of rAAV1 1243:1294 Therefore, combinations of structural and of serotype-specific cell-targeting properties of rAAV1 determine its complex immunogenicity. 25881000 6 30 theme structural 1225:1234 arg1 combinations 1209:1220 combinations 1209:1220 combinations of structural and of serotype-specific cell-targeting properties of rAAV1 1209:1294 Therefore, combinations of structural and of serotype-specific cell-targeting properties of rAAV1 determine its complex immunogenicity. 25881000 3 31 theme vector 592:597 arg1 tropism 606:612 the vector tissue tropism 588:612 the vector tissue tropism 588:612 We herein show that binding motifs recognized by the capsid and which determine the vector tissue tropism are also critical for key immune activation processes. 25881000 4 32 theme α2,6 767:770 arg1 acids 788:792 α2,3 and α2,6 N-linked sialic acids 758:792 α2,3 and α2,6 N-linked sialic acids 758:792 Using rAAV capsid serotype 1 (rAAV1) vectors which primary receptors on target cells are α2,3 and α2,6 N-linked sialic acids, we show that sialic acid-dependent binding of rAAV1 on APCs is essential to trigger CD4(+) T-cell responses by increasing rAAV1 uptake and contributing to antigenic presentation of both the capsid and transgene product although this involves different APCs. 25881000 4 32 theme α2,6 767:770 arg1 receptors 728:736 primary receptors 720:736 primary receptors on target cells 720:752 Using rAAV capsid serotype 1 (rAAV1) vectors which primary receptors on target cells are α2,3 and α2,6 N-linked sialic acids, we show that sialic acid-dependent binding of rAAV1 on APCs is essential to trigger CD4(+) T-cell responses by increasing rAAV1 uptake and contributing to antigenic presentation of both the capsid and transgene product although this involves different APCs. 25881000 4 33 theme serotype 687:694 arg1 vectors 706:712 rAAV capsid serotype 1 (rAAV1) vectors 675:712 rAAV capsid serotype 1 (rAAV1) vectors which primary receptors on target cells are α2,3 and α2,6 N-linked sialic acids 675:792 Using rAAV capsid serotype 1 (rAAV1) vectors which primary receptors on target cells are α2,3 and α2,6 N-linked sialic acids, we show that sialic acid-dependent binding of rAAV1 on APCs is essential to trigger CD4(+) T-cell responses by increasing rAAV1 uptake and contributing to antigenic presentation of both the capsid and transgene product although this involves different APCs. 25881000 4 34 theme target 741:746 arg1 cells 748:752 target cells 741:752 target cells 741:752 Using rAAV capsid serotype 1 (rAAV1) vectors which primary receptors on target cells are α2,3 and α2,6 N-linked sialic acids, we show that sialic acid-dependent binding of rAAV1 on APCs is essential to trigger CD4(+) T-cell responses by increasing rAAV1 uptake and contributing to antigenic presentation of both the capsid and transgene product although this involves different APCs. 25881000 4 35 theme α2,3 758:761 arg1 acids 788:792 α2,3 and α2,6 N-linked sialic acids 758:792 α2,3 and α2,6 N-linked sialic acids 758:792 Using rAAV capsid serotype 1 (rAAV1) vectors which primary receptors on target cells are α2,3 and α2,6 N-linked sialic acids, we show that sialic acid-dependent binding of rAAV1 on APCs is essential to trigger CD4(+) T-cell responses by increasing rAAV1 uptake and contributing to antigenic presentation of both the capsid and transgene product although this involves different APCs. 25881000 4 35 theme α2,3 758:761 arg1 receptors 728:736 primary receptors 720:736 primary receptors on target cells 720:752 Using rAAV capsid serotype 1 (rAAV1) vectors which primary receptors on target cells are α2,3 and α2,6 N-linked sialic acids, we show that sialic acid-dependent binding of rAAV1 on APCs is essential to trigger CD4(+) T-cell responses by increasing rAAV1 uptake and contributing to antigenic presentation of both the capsid and transgene product although this involves different APCs. 25881000 2 36 theme interactions 434:445 arg1 impact 418:423 the impact 414:423 the impact of these interactions on transgene or capsid-specific immunization 414:490 Molecular interactions between rAAV and various types of antigen-presenting cells (APCs), as well as the impact of these interactions on transgene or capsid-specific immunization remain unclear. 25881000 2 36 theme interactions 434:445 arg1 interactions 323:334 Molecular interactions 313:334 Molecular interactions between rAAV and various types of antigen-presenting cells (APCs) 313:400 Molecular interactions between rAAV and various types of antigen-presenting cells (APCs), as well as the impact of these interactions on transgene or capsid-specific immunization remain unclear. 25881000 4 37 theme T-cell 886:891 arg1 responses 893:901 CD4(+) T-cell responses 879:901 CD4(+) T-cell responses 879:901 Using rAAV capsid serotype 1 (rAAV1) vectors which primary receptors on target cells are α2,3 and α2,6 N-linked sialic acids, we show that sialic acid-dependent binding of rAAV1 on APCs is essential to trigger CD4(+) T-cell responses by increasing rAAV1 uptake and contributing to antigenic presentation of both the capsid and transgene product although this involves different APCs. 25881000 1 38 theme immunogenic 125:135 arg1 properties 137:146 The immunogenic properties 121:146 The immunogenic properties of recombinant adeno-associated virus (rAAV) gene transfer vectors 121:213 The immunogenic properties of recombinant adeno-associated virus (rAAV) gene transfer vectors remain incompletely characterized in spite of their usage as gene therapy vectors or as vaccines. 25881000 4 39 theme rAAV1 699:703 arg1 vectors 706:712 rAAV capsid serotype 1 (rAAV1) vectors 675:712 rAAV capsid serotype 1 (rAAV1) vectors which primary receptors on target cells are α2,3 and α2,6 N-linked sialic acids 675:792 Using rAAV capsid serotype 1 (rAAV1) vectors which primary receptors on target cells are α2,3 and α2,6 N-linked sialic acids, we show that sialic acid-dependent binding of rAAV1 on APCs is essential to trigger CD4(+) T-cell responses by increasing rAAV1 uptake and contributing to antigenic presentation of both the capsid and transgene product although this involves different APCs. 25881000 4 40 theme sialic 808:813 arg1 binding 830:836 sialic acid-dependent binding 808:836 sialic acid-dependent binding of rAAV1 on APCs 808:853 Using rAAV capsid serotype 1 (rAAV1) vectors which primary receptors on target cells are α2,3 and α2,6 N-linked sialic acids, we show that sialic acid-dependent binding of rAAV1 on APCs is essential to trigger CD4(+) T-cell responses by increasing rAAV1 uptake and contributing to antigenic presentation of both the capsid and transgene product although this involves different APCs. 25881000 0 41 theme Nanoparticle 41:52 arg1 Characteristics 54:68 Nanoparticle Characteristics 41:68 Nanoparticle Characteristics 41:68 Serotype-specific Binding Properties and Nanoparticle Characteristics Contribute to the Immunogenicity of rAAV1 Vectors. 25881000 7 42 theme variants 1392:1399 arg1 selection 1374:1382 a selection 1372:1382 a selection of rAAV variants 1372:1399 These findings may be useful to guide a selection of rAAV variants depending on the intended level of immunogenicity for either gene therapy or vaccination applications. 25881000 3 43 theme activation 647:656 arg1 processes 658:666 key immune activation processes 636:666 key immune activation processes 636:666 We herein show that binding motifs recognized by the capsid and which determine the vector tissue tropism are also critical for key immune activation processes. 25881000 7 44 theme rAAV 1387:1390 arg1 variants 1392:1399 rAAV variants 1387:1399 rAAV variants 1387:1399 These findings may be useful to guide a selection of rAAV variants depending on the intended level of immunogenicity for either gene therapy or vaccination applications. 25881000 4 45 from binding 830:836 arg1 APCs 850:853 APCs 850:853 APCs 850:853 Using rAAV capsid serotype 1 (rAAV1) vectors which primary receptors on target cells are α2,3 and α2,6 N-linked sialic acids, we show that sialic acid-dependent binding of rAAV1 on APCs is essential to trigger CD4(+) T-cell responses by increasing rAAV1 uptake and contributing to antigenic presentation of both the capsid and transgene product although this involves different APCs. 25881000 7 46 theme gene 1462:1465 arg1 therapy 1467:1473 gene therapy 1462:1473 gene therapy 1462:1473 These findings may be useful to guide a selection of rAAV variants depending on the intended level of immunogenicity for either gene therapy or vaccination applications. 25881000 3 47 theme tissue 599:604 arg1 tropism 606:612 the vector tissue tropism 588:612 the vector tissue tropism 588:612 We herein show that binding motifs recognized by the capsid and which determine the vector tissue tropism are also critical for key immune activation processes. 25881000 2 48 theme antigen-presenting 370:387 arg1 APCs 396:399 APCs 396:399 APCs 396:399 Molecular interactions between rAAV and various types of antigen-presenting cells (APCs), as well as the impact of these interactions on transgene or capsid-specific immunization remain unclear. 25881000 2 48 theme antigen-presenting 370:387 arg1 cells 389:393 antigen-presenting cells 370:393 antigen-presenting cells (APCs) 370:400 Molecular interactions between rAAV and various types of antigen-presenting cells (APCs), as well as the impact of these interactions on transgene or capsid-specific immunization remain unclear. 25881000 2 49 theme capsid-specific 463:477 arg1 immunization 479:490 capsid-specific immunization 463:490 capsid-specific immunization 463:490 Molecular interactions between rAAV and various types of antigen-presenting cells (APCs), as well as the impact of these interactions on transgene or capsid-specific immunization remain unclear. 25881000 4 50 theme CD4 879:881 arg1 responses 893:901 CD4(+) T-cell responses 879:901 CD4(+) T-cell responses 879:901 Using rAAV capsid serotype 1 (rAAV1) vectors which primary receptors on target cells are α2,3 and α2,6 N-linked sialic acids, we show that sialic acid-dependent binding of rAAV1 on APCs is essential to trigger CD4(+) T-cell responses by increasing rAAV1 uptake and contributing to antigenic presentation of both the capsid and transgene product although this involves different APCs. 25881000 4 51 theme acid-dependent 815:828 arg1 binding 830:836 sialic acid-dependent binding 808:836 sialic acid-dependent binding of rAAV1 on APCs 808:853 Using rAAV capsid serotype 1 (rAAV1) vectors which primary receptors on target cells are α2,3 and α2,6 N-linked sialic acids, we show that sialic acid-dependent binding of rAAV1 on APCs is essential to trigger CD4(+) T-cell responses by increasing rAAV1 uptake and contributing to antigenic presentation of both the capsid and transgene product although this involves different APCs. 25881000 3 52 theme binding 528:534 arg1 motifs 536:541 binding motifs 528:541 binding motifs recognized by the capsid and which determine the vector tissue tropism 528:612 We herein show that binding motifs recognized by the capsid and which determine the vector tissue tropism are also critical for key immune activation processes. 25881000 4 53 link N-linked 772:779 arg1 acids 788:792 α2,3 and α2,6 N-linked sialic acids 758:792 α2,3 and α2,6 N-linked sialic acids 758:792 Using rAAV capsid serotype 1 (rAAV1) vectors which primary receptors on target cells are α2,3 and α2,6 N-linked sialic acids, we show that sialic acid-dependent binding of rAAV1 on APCs is essential to trigger CD4(+) T-cell responses by increasing rAAV1 uptake and contributing to antigenic presentation of both the capsid and transgene product although this involves different APCs. 25881000 4 53 link N-linked 772:779 arg1 receptors 728:736 primary receptors 720:736 primary receptors on target cells 720:752 Using rAAV capsid serotype 1 (rAAV1) vectors which primary receptors on target cells are α2,3 and α2,6 N-linked sialic acids, we show that sialic acid-dependent binding of rAAV1 on APCs is essential to trigger CD4(+) T-cell responses by increasing rAAV1 uptake and contributing to antigenic presentation of both the capsid and transgene product although this involves different APCs. 25881000 3 54 theme key 636:638 arg1 processes 658:666 key immune activation processes 636:666 key immune activation processes 636:666 We herein show that binding motifs recognized by the capsid and which determine the vector tissue tropism are also critical for key immune activation processes. 25881000 7 55 theme intended 1418:1425 arg1 level 1427:1431 the intended level 1414:1431 the intended level of immunogenicity for either gene therapy or vaccination applications 1414:1501 These findings may be useful to guide a selection of rAAV variants depending on the intended level of immunogenicity for either gene therapy or vaccination applications. 25881000 1 56 theme recombinant 151:161 arg1 vectors 207:213 recombinant adeno-associated virus (rAAV) gene transfer vectors 151:213 recombinant adeno-associated virus (rAAV) gene transfer vectors 151:213 The immunogenic properties of recombinant adeno-associated virus (rAAV) gene transfer vectors remain incompletely characterized in spite of their usage as gene therapy vectors or as vaccines. 25881000 4 57 from receptors 728:736 arg1 cells 748:752 target cells 741:752 target cells 741:752 Using rAAV capsid serotype 1 (rAAV1) vectors which primary receptors on target cells are α2,3 and α2,6 N-linked sialic acids, we show that sialic acid-dependent binding of rAAV1 on APCs is essential to trigger CD4(+) T-cell responses by increasing rAAV1 uptake and contributing to antigenic presentation of both the capsid and transgene product although this involves different APCs. 25881000 4 58 theme N-linked 772:779 arg1 acids 788:792 α2,3 and α2,6 N-linked sialic acids 758:792 α2,3 and α2,6 N-linked sialic acids 758:792 Using rAAV capsid serotype 1 (rAAV1) vectors which primary receptors on target cells are α2,3 and α2,6 N-linked sialic acids, we show that sialic acid-dependent binding of rAAV1 on APCs is essential to trigger CD4(+) T-cell responses by increasing rAAV1 uptake and contributing to antigenic presentation of both the capsid and transgene product although this involves different APCs. 25881000 4 58 theme N-linked 772:779 arg1 receptors 728:736 primary receptors 720:736 primary receptors on target cells 720:752 Using rAAV capsid serotype 1 (rAAV1) vectors which primary receptors on target cells are α2,3 and α2,6 N-linked sialic acids, we show that sialic acid-dependent binding of rAAV1 on APCs is essential to trigger CD4(+) T-cell responses by increasing rAAV1 uptake and contributing to antigenic presentation of both the capsid and transgene product although this involves different APCs. 25881000 3 59 theme immune 640:645 arg1 processes 658:666 key immune activation processes 636:666 key immune activation processes 636:666 We herein show that binding motifs recognized by the capsid and which determine the vector tissue tropism are also critical for key immune activation processes. 25881000 2 60 from impact 418:423 arg1 transgene 450:458 transgene 450:458 transgene 450:458 Molecular interactions between rAAV and various types of antigen-presenting cells (APCs), as well as the impact of these interactions on transgene or capsid-specific immunization remain unclear. 25881000 2 60 from impact 418:423 arg1 immunization 479:490 capsid-specific immunization 463:490 capsid-specific immunization 463:490 Molecular interactions between rAAV and various types of antigen-presenting cells (APCs), as well as the impact of these interactions on transgene or capsid-specific immunization remain unclear. 25881000 2 61 theme various 353:359 arg1 types 361:365 various types 353:365 various types of antigen-presenting cells (APCs) 353:400 Molecular interactions between rAAV and various types of antigen-presenting cells (APCs), as well as the impact of these interactions on transgene or capsid-specific immunization remain unclear. 25881000 4 62 theme antigenic 950:958 arg1 presentation 960:971 antigenic presentation 950:971 antigenic presentation of both the capsid and transgene product 950:1012 Using rAAV capsid serotype 1 (rAAV1) vectors which primary receptors on target cells are α2,3 and α2,6 N-linked sialic acids, we show that sialic acid-dependent binding of rAAV1 on APCs is essential to trigger CD4(+) T-cell responses by increasing rAAV1 uptake and contributing to antigenic presentation of both the capsid and transgene product although this involves different APCs. 25881000 1 63 theme virus 180:184 arg1 vectors 207:213 recombinant adeno-associated virus (rAAV) gene transfer vectors 151:213 recombinant adeno-associated virus (rAAV) gene transfer vectors 151:213 The immunogenic properties of recombinant adeno-associated virus (rAAV) gene transfer vectors remain incompletely characterized in spite of their usage as gene therapy vectors or as vaccines. 25881000 4 64 theme rAAV 675:678 arg1 vectors 706:712 rAAV capsid serotype 1 (rAAV1) vectors 675:712 rAAV capsid serotype 1 (rAAV1) vectors which primary receptors on target cells are α2,3 and α2,6 N-linked sialic acids 675:792 Using rAAV capsid serotype 1 (rAAV1) vectors which primary receptors on target cells are α2,3 and α2,6 N-linked sialic acids, we show that sialic acid-dependent binding of rAAV1 on APCs is essential to trigger CD4(+) T-cell responses by increasing rAAV1 uptake and contributing to antigenic presentation of both the capsid and transgene product although this involves different APCs. 25881000 5 65 theme vector 1103:1108 arg1 sufficient 1134:1143 sufficient 1134:1143 sufficient 1134:1143 In addition, the nanoparticulate structure of the vector in itself appears to be sufficient to trigger mobilization and activation of some APCs. 25881000 5 65 theme vector 1103:1108 arg1 structure 1086:1094 the nanoparticulate structure 1066:1094 the nanoparticulate structure of the vector in itself 1066:1118 In addition, the nanoparticulate structure of the vector in itself appears to be sufficient to trigger mobilization and activation of some APCs. 25881000 5 66 from structure 1086:1094 arg1 itself 1113:1118 itself 1113:1118 itself 1113:1118 In addition, the nanoparticulate structure of the vector in itself appears to be sufficient to trigger mobilization and activation of some APCs. 25881000 4 67 theme product 1006:1012 arg1 presentation 960:971 antigenic presentation 950:971 antigenic presentation of both the capsid and transgene product 950:1012 Using rAAV capsid serotype 1 (rAAV1) vectors which primary receptors on target cells are α2,3 and α2,6 N-linked sialic acids, we show that sialic acid-dependent binding of rAAV1 on APCs is essential to trigger CD4(+) T-cell responses by increasing rAAV1 uptake and contributing to antigenic presentation of both the capsid and transgene product although this involves different APCs. 25881000 4 68 theme different 1037:1045 arg1 APCs 1047:1050 different APCs 1037:1050 different APCs 1037:1050 Using rAAV capsid serotype 1 (rAAV1) vectors which primary receptors on target cells are α2,3 and α2,6 N-linked sialic acids, we show that sialic acid-dependent binding of rAAV1 on APCs is essential to trigger CD4(+) T-cell responses by increasing rAAV1 uptake and contributing to antigenic presentation of both the capsid and transgene product although this involves different APCs. 25881000 4 69 theme rAAV1 917:921 arg1 uptake 923:928 rAAV1 uptake 917:928 rAAV1 uptake 917:928 Using rAAV capsid serotype 1 (rAAV1) vectors which primary receptors on target cells are α2,3 and α2,6 N-linked sialic acids, we show that sialic acid-dependent binding of rAAV1 on APCs is essential to trigger CD4(+) T-cell responses by increasing rAAV1 uptake and contributing to antigenic presentation of both the capsid and transgene product although this involves different APCs. 25423599 5 0 theme heteromeric 799:809 arg1 channels 816:823 the heteromeric HCN2 channels 795:823 the heteromeric HCN2 channels of WT and glycosylation-defective N380Q 795:863 Interestingly, the heteromeric HCN2 channels of WT and glycosylation-defective N380Q have been observed on cell membranes, indicating that not all four subunits of a tetrameric HCN2 channel need to be glycosylated for HCN2 channels to traffic to plasma membranes. 25423599 1 1 theme membrane 182:189 arg1 hyperpolarization 191:207 membrane hyperpolarization 182:207 membrane hyperpolarization 182:207 Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are activated by membrane hyperpolarization and conduct an inward cation current, which contributes to rhythmic electrical activity of neural and cardiac pacemaker cells. 25423599 5 2 theme HCN2 811:814 arg1 channels 816:823 the heteromeric HCN2 channels 795:823 the heteromeric HCN2 channels of WT and glycosylation-defective N380Q 795:863 Interestingly, the heteromeric HCN2 channels of WT and glycosylation-defective N380Q have been observed on cell membranes, indicating that not all four subunits of a tetrameric HCN2 channel need to be glycosylated for HCN2 channels to traffic to plasma membranes. 25423599 2 3 link N-linked 376:383 arg1 glycosylation 385:397 N-linked glycosylation 376:397 N-linked glycosylation 376:397 HCN channels have been shown to undergo N-linked glycosylation, and the N-glycosylation has been shown to be required for membrane trafficking and possibly function. 25423599 7 4 theme fluorescence-based 1152:1169 arg1 assay 1176:1180 a fluorescence-based flux assay 1150:1180 a fluorescence-based flux assay 1150:1180 We developed a fluorescence-based flux assay, which makes it possible to establish a negative potential inside liposomes to open HCN2 channels. 25423599 6 5 theme HCN2 1122:1125 arg1 channels 1127:1134 HCN2 channels 1122:1134 HCN2 channels 1122:1134 Subsequently, we investigate the effect of N-glycosylation on the function of HCN2 channels. 25423599 0 6 from Effects 0:6 arg1 channels 88:95 hyperpolarization-activated cyclic nucleotide-gated (HCN) channels 30:95 hyperpolarization-activated cyclic nucleotide-gated (HCN) channels 30:95 Effects of N-glycosylation on hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. 25423599 3 7 theme HCN2 578:581 arg1 channels 583:590 HCN2 channels 578:590 HCN2 channels 578:590 In this study, recombinant wild-type (WT) and glycosylation-defective N380Q HCN2 channels were individually or co-expressed in HEK-293 cells. 25423599 8 8 theme HCN2 1422:1425 arg1 channels 1427:1434 WT HCN2 channels 1419:1434 WT HCN2 channels 1419:1434 Using this flux assay, we demonstrate that glycosylation-defective N380Q HCN2 channels reconstituted into liposomes function similarly to WT HCN2 channels. 25423599 1 9 theme neural 300:305 arg1 cells 329:333 neural and cardiac pacemaker cells 300:333 neural and cardiac pacemaker cells 300:333 Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are activated by membrane hyperpolarization and conduct an inward cation current, which contributes to rhythmic electrical activity of neural and cardiac pacemaker cells. 25423599 8 10 theme WT 1419:1420 arg1 channels 1427:1434 WT HCN2 channels 1419:1434 WT HCN2 channels 1419:1434 Using this flux assay, we demonstrate that glycosylation-defective N380Q HCN2 channels reconstituted into liposomes function similarly to WT HCN2 channels. 25423599 9 11 gly N-glycosylation 1456:1470 arg1 HCN2 1492:1495 HCN2 channels 1492:1504 HCN2 channels to function 1492:1516 This suggests that N-glycosylation is not required for HCN2 channels to function. 25423599 5 12 theme HCN2 998:1001 arg1 channels 1003:1010 HCN2 channels 998:1010 HCN2 channels 998:1010 Interestingly, the heteromeric HCN2 channels of WT and glycosylation-defective N380Q have been observed on cell membranes, indicating that not all four subunits of a tetrameric HCN2 channel need to be glycosylated for HCN2 channels to traffic to plasma membranes. 25423599 5 13 theme channel 962:968 arg1 subunits 932:939 not all four subunits 919:939 not all four subunits of a tetrameric HCN2 channel 919:968 Interestingly, the heteromeric HCN2 channels of WT and glycosylation-defective N380Q have been observed on cell membranes, indicating that not all four subunits of a tetrameric HCN2 channel need to be glycosylated for HCN2 channels to traffic to plasma membranes. 25423599 5 14 gly glycosylated 981:992 arg1 subunits 932:939 not all four subunits 919:939 not all four subunits of a tetrameric HCN2 channel 919:968 Interestingly, the heteromeric HCN2 channels of WT and glycosylation-defective N380Q have been observed on cell membranes, indicating that not all four subunits of a tetrameric HCN2 channel need to be glycosylated for HCN2 channels to traffic to plasma membranes. 25423599 2 15 theme N-linked 376:383 arg1 glycosylation 385:397 N-linked glycosylation 376:397 N-linked glycosylation 376:397 HCN channels have been shown to undergo N-linked glycosylation, and the N-glycosylation has been shown to be required for membrane trafficking and possibly function. 25423599 4 16 gly glycosylation 664:676 arg1 channels 758:765 HCN channels 754:765 HCN channels in the cell 754:777 We demonstrate that glycosylation is required for trafficking to the plasma membrane and for the stability of HCN channels in the cell. 25423599 3 17 theme glycosylation-defective 548:570 arg1 N380Q 572:576 glycosylation-defective N380Q 548:576 glycosylation-defective N380Q 548:576 In this study, recombinant wild-type (WT) and glycosylation-defective N380Q HCN2 channels were individually or co-expressed in HEK-293 cells. 25423599 7 18 theme flux 1171:1174 arg1 assay 1176:1180 a fluorescence-based flux assay 1150:1180 a fluorescence-based flux assay 1150:1180 We developed a fluorescence-based flux assay, which makes it possible to establish a negative potential inside liposomes to open HCN2 channels. 25423599 3 19 dep wild-type 529:537 arg1 WT 540:541 WT 540:541 WT 540:541 In this study, recombinant wild-type (WT) and glycosylation-defective N380Q HCN2 channels were individually or co-expressed in HEK-293 cells. 25423599 3 19 dep wild-type 529:537 arg1 channels 583:590 HCN2 channels 578:590 HCN2 channels 578:590 In this study, recombinant wild-type (WT) and glycosylation-defective N380Q HCN2 channels were individually or co-expressed in HEK-293 cells. 25423599 9 20 theme HCN2 1492:1495 arg1 channels 1497:1504 HCN2 channels 1492:1504 HCN2 channels to function 1492:1516 This suggests that N-glycosylation is not required for HCN2 channels to function. 25423599 5 21 theme glycosylation-defective 835:857 arg1 N380Q 859:863 glycosylation-defective N380Q 835:863 glycosylation-defective N380Q 835:863 Interestingly, the heteromeric HCN2 channels of WT and glycosylation-defective N380Q have been observed on cell membranes, indicating that not all four subunits of a tetrameric HCN2 channel need to be glycosylated for HCN2 channels to traffic to plasma membranes. 25423599 2 22 gly N-glycosylation 408:422 arg1 membrane 458:465 membrane trafficking 458:477 membrane trafficking 458:477 HCN channels have been shown to undergo N-linked glycosylation, and the N-glycosylation has been shown to be required for membrane trafficking and possibly function. 25423599 1 23 theme Hyperpolarization-activated 98:124 arg1 channels 156:163 Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels 98:163 Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels 98:163 Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are activated by membrane hyperpolarization and conduct an inward cation current, which contributes to rhythmic electrical activity of neural and cardiac pacemaker cells. 25423599 5 24 theme N380Q 859:863 arg1 channels 816:823 the heteromeric HCN2 channels 795:823 the heteromeric HCN2 channels of WT and glycosylation-defective N380Q 795:863 Interestingly, the heteromeric HCN2 channels of WT and glycosylation-defective N380Q have been observed on cell membranes, indicating that not all four subunits of a tetrameric HCN2 channel need to be glycosylated for HCN2 channels to traffic to plasma membranes. 25423599 1 25 theme cardiac 311:317 arg1 cells 329:333 neural and cardiac pacemaker cells 300:333 neural and cardiac pacemaker cells 300:333 Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are activated by membrane hyperpolarization and conduct an inward cation current, which contributes to rhythmic electrical activity of neural and cardiac pacemaker cells. 25423599 4 26 from cell 774:777 arg1 stability 741:749 the stability 737:749 the stability of HCN channels in the cell 737:777 We demonstrate that glycosylation is required for trafficking to the plasma membrane and for the stability of HCN channels in the cell. 25423599 1 27 theme cyclic 126:131 arg1 channels 156:163 Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels 98:163 Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels 98:163 Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are activated by membrane hyperpolarization and conduct an inward cation current, which contributes to rhythmic electrical activity of neural and cardiac pacemaker cells. 25423599 1 28 theme inward 224:229 arg1 current 238:244 an inward cation current 221:244 an inward cation current 221:244 Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are activated by membrane hyperpolarization and conduct an inward cation current, which contributes to rhythmic electrical activity of neural and cardiac pacemaker cells. 25423599 1 29 theme pacemaker 319:327 arg1 cells 329:333 neural and cardiac pacemaker cells 300:333 neural and cardiac pacemaker cells 300:333 Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are activated by membrane hyperpolarization and conduct an inward cation current, which contributes to rhythmic electrical activity of neural and cardiac pacemaker cells. 25423599 6 30 from effect 1077:1082 arg1 function 1110:1117 the function 1106:1117 the function of HCN2 channels 1106:1134 Subsequently, we investigate the effect of N-glycosylation on the function of HCN2 channels. 25423599 1 31 theme nucleotide-gated 133:148 arg1 channels 156:163 Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels 98:163 Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels 98:163 Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are activated by membrane hyperpolarization and conduct an inward cation current, which contributes to rhythmic electrical activity of neural and cardiac pacemaker cells. 25423599 1 32 theme cation 231:236 arg1 current 238:244 an inward cation current 221:244 an inward cation current 221:244 Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are activated by membrane hyperpolarization and conduct an inward cation current, which contributes to rhythmic electrical activity of neural and cardiac pacemaker cells. 25423599 0 33 theme N-glycosylation 11:25 arg1 Effects 0:6 Effects 0:6 Effects of N-glycosylation on hyperpolarization-activated cyclic nucleotide-gated (HCN) channels 0:95 Effects of N-glycosylation on hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. 25423599 1 34 theme cells 329:333 arg1 activity 288:295 rhythmic electrical activity 268:295 rhythmic electrical activity of neural and cardiac pacemaker cells 268:333 Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are activated by membrane hyperpolarization and conduct an inward cation current, which contributes to rhythmic electrical activity of neural and cardiac pacemaker cells. 25423599 2 35 theme HCN 336:338 arg1 channels 340:347 HCN channels 336:347 HCN channels 336:347 HCN channels have been shown to undergo N-linked glycosylation, and the N-glycosylation has been shown to be required for membrane trafficking and possibly function. 25423599 0 36 theme cyclic 58:63 arg1 channels 88:95 hyperpolarization-activated cyclic nucleotide-gated (HCN) channels 30:95 hyperpolarization-activated cyclic nucleotide-gated (HCN) channels 30:95 Effects of N-glycosylation on hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. 25423599 2 37 gly glycosylation 385:397 arg1 channels 340:347 HCN channels 336:347 HCN channels 336:347 HCN channels have been shown to undergo N-linked glycosylation, and the N-glycosylation has been shown to be required for membrane trafficking and possibly function. 25423599 4 38 theme plasma 713:718 arg1 membrane 720:727 the plasma membrane 709:727 the plasma membrane 709:727 We demonstrate that glycosylation is required for trafficking to the plasma membrane and for the stability of HCN channels in the cell. 25423599 5 39 theme cell 887:890 arg1 membranes 892:900 cell membranes 887:900 cell membranes 887:900 Interestingly, the heteromeric HCN2 channels of WT and glycosylation-defective N380Q have been observed on cell membranes, indicating that not all four subunits of a tetrameric HCN2 channel need to be glycosylated for HCN2 channels to traffic to plasma membranes. 25423599 0 40 theme hyperpolarization-activated 30:56 arg1 channels 88:95 hyperpolarization-activated cyclic nucleotide-gated (HCN) channels 30:95 hyperpolarization-activated cyclic nucleotide-gated (HCN) channels 30:95 Effects of N-glycosylation on hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. 25423599 8 41 theme N380Q 1348:1352 arg1 channels 1359:1366 glycosylation-defective N380Q HCN2 channels 1324:1366 glycosylation-defective N380Q HCN2 channels reconstituted into liposomes 1324:1395 Using this flux assay, we demonstrate that glycosylation-defective N380Q HCN2 channels reconstituted into liposomes function similarly to WT HCN2 channels. 25423599 5 42 theme WT 828:829 arg1 channels 816:823 the heteromeric HCN2 channels 795:823 the heteromeric HCN2 channels of WT and glycosylation-defective N380Q 795:863 Interestingly, the heteromeric HCN2 channels of WT and glycosylation-defective N380Q have been observed on cell membranes, indicating that not all four subunits of a tetrameric HCN2 channel need to be glycosylated for HCN2 channels to traffic to plasma membranes. 25423599 7 43 theme negative 1222:1229 arg1 potential 1231:1239 a negative potential 1220:1239 a negative potential inside liposomes to open HCN2 channels 1220:1278 We developed a fluorescence-based flux assay, which makes it possible to establish a negative potential inside liposomes to open HCN2 channels. 25423599 7 44 theme open 1261:1264 arg1 channels 1271:1278 open HCN2 channels 1261:1278 open HCN2 channels 1261:1278 We developed a fluorescence-based flux assay, which makes it possible to establish a negative potential inside liposomes to open HCN2 channels. 25423599 0 45 gly N-glycosylation 11:25 arg1 HCN 83:85 hyperpolarization-activated cyclic nucleotide-gated (HCN) channels 30:95 hyperpolarization-activated cyclic nucleotide-gated (HCN) channels 30:95 Effects of N-glycosylation on hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. 25423599 0 45 gly N-glycosylation 11:25 arg1 nucleotide-gated 65:80 hyperpolarization-activated cyclic nucleotide-gated (HCN) channels 30:95 hyperpolarization-activated cyclic nucleotide-gated (HCN) channels 30:95 Effects of N-glycosylation on hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. 25423599 6 46 gly N-glycosylation 1087:1101 arg1 channels 1127:1134 HCN2 channels 1122:1134 HCN2 channels 1122:1134 Subsequently, we investigate the effect of N-glycosylation on the function of HCN2 channels. 25423599 1 47 theme HCN 151:153 arg1 channels 156:163 Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels 98:163 Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels 98:163 Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are activated by membrane hyperpolarization and conduct an inward cation current, which contributes to rhythmic electrical activity of neural and cardiac pacemaker cells. 25423599 0 48 theme nucleotide-gated 65:80 arg1 channels 88:95 hyperpolarization-activated cyclic nucleotide-gated (HCN) channels 30:95 hyperpolarization-activated cyclic nucleotide-gated (HCN) channels 30:95 Effects of N-glycosylation on hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. 25423599 3 49 theme HEK-293 629:635 arg1 cells 637:641 HEK-293 cells 629:641 HEK-293 cells 629:641 In this study, recombinant wild-type (WT) and glycosylation-defective N380Q HCN2 channels were individually or co-expressed in HEK-293 cells. 25423599 5 50 theme tetrameric 946:955 arg1 channel 962:968 a tetrameric HCN2 channel 944:968 a tetrameric HCN2 channel 944:968 Interestingly, the heteromeric HCN2 channels of WT and glycosylation-defective N380Q have been observed on cell membranes, indicating that not all four subunits of a tetrameric HCN2 channel need to be glycosylated for HCN2 channels to traffic to plasma membranes. 25423599 7 51 theme HCN2 1266:1269 arg1 channels 1271:1278 open HCN2 channels 1261:1278 open HCN2 channels 1261:1278 We developed a fluorescence-based flux assay, which makes it possible to establish a negative potential inside liposomes to open HCN2 channels. 25423599 4 52 theme HCN 754:756 arg1 channels 758:765 HCN channels 754:765 HCN channels in the cell 754:777 We demonstrate that glycosylation is required for trafficking to the plasma membrane and for the stability of HCN channels in the cell. 25423599 5 53 located observed 875:882 arg2 channels 816:823 the heteromeric HCN2 channels 795:823 the heteromeric HCN2 channels of WT and glycosylation-defective N380Q 795:863 Interestingly, the heteromeric HCN2 channels of WT and glycosylation-defective N380Q have been observed on cell membranes, indicating that not all four subunits of a tetrameric HCN2 channel need to be glycosylated for HCN2 channels to traffic to plasma membranes. 25423599 5 53 located observed 875:882 arg1 membranes 892:900 cell membranes 887:900 cell membranes 887:900 Interestingly, the heteromeric HCN2 channels of WT and glycosylation-defective N380Q have been observed on cell membranes, indicating that not all four subunits of a tetrameric HCN2 channel need to be glycosylated for HCN2 channels to traffic to plasma membranes. 25423599 5 54 theme HCN2 957:960 arg1 channel 962:968 a tetrameric HCN2 channel 944:968 a tetrameric HCN2 channel 944:968 Interestingly, the heteromeric HCN2 channels of WT and glycosylation-defective N380Q have been observed on cell membranes, indicating that not all four subunits of a tetrameric HCN2 channel need to be glycosylated for HCN2 channels to traffic to plasma membranes. 25423599 4 55 from channels 758:765 arg1 cell 774:777 the cell 770:777 the cell 770:777 We demonstrate that glycosylation is required for trafficking to the plasma membrane and for the stability of HCN channels in the cell. 25423599 6 56 theme N-glycosylation 1087:1101 arg1 effect 1077:1082 the effect 1073:1082 the effect of N-glycosylation on the function of HCN2 channels 1073:1134 Subsequently, we investigate the effect of N-glycosylation on the function of HCN2 channels. 25423599 4 57 theme channels 758:765 arg1 stability 741:749 the stability 737:749 the stability of HCN channels in the cell 737:777 We demonstrate that glycosylation is required for trafficking to the plasma membrane and for the stability of HCN channels in the cell. 25423599 8 58 theme glycosylation-defective 1324:1346 arg1 channels 1359:1366 glycosylation-defective N380Q HCN2 channels 1324:1366 glycosylation-defective N380Q HCN2 channels reconstituted into liposomes 1324:1395 Using this flux assay, we demonstrate that glycosylation-defective N380Q HCN2 channels reconstituted into liposomes function similarly to WT HCN2 channels. 25423599 5 59 theme plasma 1026:1031 arg1 membranes 1033:1041 plasma membranes 1026:1041 plasma membranes 1026:1041 Interestingly, the heteromeric HCN2 channels of WT and glycosylation-defective N380Q have been observed on cell membranes, indicating that not all four subunits of a tetrameric HCN2 channel need to be glycosylated for HCN2 channels to traffic to plasma membranes. 25423599 8 60 theme flux 1292:1295 arg1 assay 1297:1301 this flux assay 1287:1301 this flux assay 1287:1301 Using this flux assay, we demonstrate that glycosylation-defective N380Q HCN2 channels reconstituted into liposomes function similarly to WT HCN2 channels. 25423599 8 61 theme HCN2 1354:1357 arg1 channels 1359:1366 glycosylation-defective N380Q HCN2 channels 1324:1366 glycosylation-defective N380Q HCN2 channels reconstituted into liposomes 1324:1395 Using this flux assay, we demonstrate that glycosylation-defective N380Q HCN2 channels reconstituted into liposomes function similarly to WT HCN2 channels. 25423599 1 62 theme rhythmic 268:275 arg1 activity 288:295 rhythmic electrical activity 268:295 rhythmic electrical activity of neural and cardiac pacemaker cells 268:333 Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are activated by membrane hyperpolarization and conduct an inward cation current, which contributes to rhythmic electrical activity of neural and cardiac pacemaker cells. 25423599 0 63 theme HCN 83:85 arg1 channels 88:95 hyperpolarization-activated cyclic nucleotide-gated (HCN) channels 30:95 hyperpolarization-activated cyclic nucleotide-gated (HCN) channels 30:95 Effects of N-glycosylation on hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. 25423599 2 64 theme membrane 458:465 arg1 trafficking 467:477 membrane trafficking 458:477 membrane trafficking 458:477 HCN channels have been shown to undergo N-linked glycosylation, and the N-glycosylation has been shown to be required for membrane trafficking and possibly function. 25423599 6 65 theme channels 1127:1134 arg1 function 1110:1117 the function 1106:1117 the function of HCN2 channels 1106:1134 Subsequently, we investigate the effect of N-glycosylation on the function of HCN2 channels. 25423599 4 66 from stability 741:749 arg1 cell 774:777 the cell 770:777 the cell 770:777 We demonstrate that glycosylation is required for trafficking to the plasma membrane and for the stability of HCN channels in the cell. 25423599 1 67 theme electrical 277:286 arg1 activity 288:295 rhythmic electrical activity 268:295 rhythmic electrical activity of neural and cardiac pacemaker cells 268:333 Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are activated by membrane hyperpolarization and conduct an inward cation current, which contributes to rhythmic electrical activity of neural and cardiac pacemaker cells. 29112822 7 0 theme immunological 1198:1210 arg1 activity 1212:1219 the immunological activity 1194:1219 the immunological activity of its conjugates 1194:1237 These results revealed not only the self-adjuvant property of MPLA conjugates to elicit robust IgG antibody responses but also the impact of MPLA structure on the immunological activity of its conjugates. 29112822 5 1 from present 883:889 arg1 cavities 926:933 the intrapleural and peritoneal cavities 894:933 the intrapleural and peritoneal cavities 894:933 It was thus speculated that MPLA conjugates might act via stimulating B1 lymphocytes present in the intrapleural and peritoneal cavities. 29112822 3 2 theme Immunological 535:547 arg1 activities 549:558 Immunological activities 535:558 Immunological activities of the two synthetic conjugates 535:590 Immunological activities of the two synthetic conjugates were evaluated in mice and compared. 29112822 0 3 theme A 116:116 arg1 Synthesis 0:8 Synthesis 0:8 Synthesis 0:8 Synthesis and Immunological Comparison of Differently Linked Lipoarabinomannan Oligosaccharide-Monophosphoryl Lipid A Conjugates as Antituberculosis Vaccines. 29112822 0 3 theme A 116:116 arg1 Comparison 28:37 Immunological Comparison 14:37 Immunological Comparison 14:37 Synthesis and Immunological Comparison of Differently Linked Lipoarabinomannan Oligosaccharide-Monophosphoryl Lipid A Conjugates as Antituberculosis Vaccines. 29112822 1 4 theme amide 374:378 arg1 bond 380:383 an amide bond 371:383 an amide bond 371:383 A monophosphoryl lipid A (MPLA) derivative having the 6'-OH group substituted with an NH2 group was synthesized and coupled with the upstream terminal tetrasaccharide of mycobacterial lipoarabinomannan (LAM) via an amide bond to create a novel type of MPLA-based fully synthetic glycoconjugate vaccine. 29112822 5 5 attach present 883:889 arg1 cavities 926:933 the intrapleural and peritoneal cavities 894:933 the intrapleural and peritoneal cavities 894:933 It was thus speculated that MPLA conjugates might act via stimulating B1 lymphocytes present in the intrapleural and peritoneal cavities. 29112822 5 5 attach present 883:889 arg2 lymphocytes 871:881 B1 lymphocytes 868:881 B1 lymphocytes present in the intrapleural and peritoneal cavities 868:933 It was thus speculated that MPLA conjugates might act via stimulating B1 lymphocytes present in the intrapleural and peritoneal cavities. 29112822 9 6 theme synthetic 1519:1527 arg1 vaccines 1558:1565 fully synthetic carbohydrate-based conjugate vaccines 1513:1565 fully synthetic carbohydrate-based conjugate vaccines 1513:1565 Additionally, the 6'-amino derivative of MPLA was proved to be a useful carrier for the development of fully synthetic carbohydrate-based conjugate vaccines. 29112822 0 7 theme Antituberculosis 132:147 arg1 Vaccines 149:156 Antituberculosis Vaccines 132:156 Antituberculosis Vaccines 132:156 Synthesis and Immunological Comparison of Differently Linked Lipoarabinomannan Oligosaccharide-Monophosphoryl Lipid A Conjugates as Antituberculosis Vaccines. 29112822 3 8 theme conjugates 581:590 arg1 activities 549:558 Immunological activities 535:558 Immunological activities of the two synthetic conjugates 535:590 Immunological activities of the two synthetic conjugates were evaluated in mice and compared. 29112822 9 9 theme carbohydrate-based 1529:1546 arg1 vaccines 1558:1565 fully synthetic carbohydrate-based conjugate vaccines 1513:1565 fully synthetic carbohydrate-based conjugate vaccines 1513:1565 Additionally, the 6'-amino derivative of MPLA was proved to be a useful carrier for the development of fully synthetic carbohydrate-based conjugate vaccines. 29112822 9 10 theme MPLA 1451:1454 arg1 derivative 1437:1446 the 6'-amino derivative 1424:1446 the 6'-amino derivative of MPLA 1424:1454 Additionally, the 6'-amino derivative of MPLA was proved to be a useful carrier for the development of fully synthetic carbohydrate-based conjugate vaccines. 29112822 9 10 theme MPLA 1451:1454 arg1 carrier 1482:1488 a useful carrier 1473:1488 a useful carrier for the development of fully synthetic carbohydrate-based conjugate vaccines 1473:1565 Additionally, the 6'-amino derivative of MPLA was proved to be a useful carrier for the development of fully synthetic carbohydrate-based conjugate vaccines. 29112822 1 11 theme upstream 292:299 arg1 tetrasaccharide 310:324 the upstream terminal tetrasaccharide 288:324 the upstream terminal tetrasaccharide of mycobacterial lipoarabinomannan (LAM) via an amide bond to create a novel type of MPLA-based fully synthetic glycoconjugate vaccine 288:459 A monophosphoryl lipid A (MPLA) derivative having the 6'-OH group substituted with an NH2 group was synthesized and coupled with the upstream terminal tetrasaccharide of mycobacterial lipoarabinomannan (LAM) via an amide bond to create a novel type of MPLA-based fully synthetic glycoconjugate vaccine. 29112822 6 12 theme antibody 974:981 arg1 titers 983:988 antibody titers 974:988 antibody titers much higher 974:1000 Moreover, the 6'-N-conjugate afforded antibody titers much higher than those of the 1-O-conjugate. 29112822 7 13 theme MPLA 1176:1179 arg1 structure 1181:1189 MPLA structure 1176:1189 MPLA structure 1176:1189 These results revealed not only the self-adjuvant property of MPLA conjugates to elicit robust IgG antibody responses but also the impact of MPLA structure on the immunological activity of its conjugates. 29112822 8 14 theme investigation 1395:1407 arg1 worthy 1377:1382 worthy 1377:1382 antituberculosis vaccines worthy of further investigation 1351:1407 It was concluded that LAM oligosaccharide-MPLA conjugates, especially 6'-N-linked, are promising candidates as antituberculosis vaccines worthy of further investigation. 29112822 9 15 theme conjugate 1548:1556 arg1 vaccines 1558:1565 fully synthetic carbohydrate-based conjugate vaccines 1513:1565 fully synthetic carbohydrate-based conjugate vaccines 1513:1565 Additionally, the 6'-amino derivative of MPLA was proved to be a useful carrier for the development of fully synthetic carbohydrate-based conjugate vaccines. 29112822 8 16 theme antituberculosis 1351:1366 arg1 vaccines 1368:1375 antituberculosis vaccines 1351:1375 antituberculosis vaccines worthy of further investigation 1351:1407 It was concluded that LAM oligosaccharide-MPLA conjugates, especially 6'-N-linked, are promising candidates as antituberculosis vaccines worthy of further investigation. 29112822 9 17 theme vaccines 1558:1565 arg1 development 1498:1508 the development 1494:1508 the development of fully synthetic carbohydrate-based conjugate vaccines 1494:1565 Additionally, the 6'-amino derivative of MPLA was proved to be a useful carrier for the development of fully synthetic carbohydrate-based conjugate vaccines. 29112822 5 18 theme B1 868:869 arg1 lymphocytes 871:881 B1 lymphocytes 868:881 B1 lymphocytes present in the intrapleural and peritoneal cavities 868:933 It was thus speculated that MPLA conjugates might act via stimulating B1 lymphocytes present in the intrapleural and peritoneal cavities. 29112822 7 19 theme structure 1181:1189 arg1 impact 1166:1171 the impact 1162:1171 not only the self-adjuvant property of MPLA conjugates to elicit robust IgG antibody responses but also the impact of MPLA structure on the immunological activity of its conjugates 1058:1237 These results revealed not only the self-adjuvant property of MPLA conjugates to elicit robust IgG antibody responses but also the impact of MPLA structure on the immunological activity of its conjugates. 29112822 7 19 theme structure 1181:1189 arg1 property 1085:1092 the self-adjuvant property 1067:1092 not only the self-adjuvant property of MPLA conjugates to elicit robust IgG antibody responses but also the impact of MPLA structure on the immunological activity of its conjugates 1058:1237 These results revealed not only the self-adjuvant property of MPLA conjugates to elicit robust IgG antibody responses but also the impact of MPLA structure on the immunological activity of its conjugates. 29112822 3 20 theme synthetic 571:579 arg1 conjugates 581:590 the two synthetic conjugates 563:590 the two synthetic conjugates 563:590 Immunological activities of the two synthetic conjugates were evaluated in mice and compared. 29112822 4 21 theme intraperitoneal 690:704 arg1 injection 706:714 intraperitoneal injection 690:714 intraperitoneal injection 690:714 Both afforded robust overall and IgG antibody responses, but intraperitoneal injection elicited responses significantly stronger than those from subcutaneous injection. 29112822 8 22 theme oligosaccharide-MPLA 1266:1285 arg1 conjugates 1287:1296 LAM oligosaccharide-MPLA conjugates 1262:1296 LAM oligosaccharide-MPLA conjugates 1262:1296 It was concluded that LAM oligosaccharide-MPLA conjugates, especially 6'-N-linked, are promising candidates as antituberculosis vaccines worthy of further investigation. 29112822 8 22 theme oligosaccharide-MPLA 1266:1285 arg1 candidates 1337:1346 promising candidates 1327:1346 promising candidates as antituberculosis vaccines worthy of further investigation 1327:1407 It was concluded that LAM oligosaccharide-MPLA conjugates, especially 6'-N-linked, are promising candidates as antituberculosis vaccines worthy of further investigation. 29112822 1 23 theme novel 397:401 arg1 type 403:406 a novel type 395:406 a novel type of MPLA-based fully synthetic glycoconjugate vaccine 395:459 A monophosphoryl lipid A (MPLA) derivative having the 6'-OH group substituted with an NH2 group was synthesized and coupled with the upstream terminal tetrasaccharide of mycobacterial lipoarabinomannan (LAM) via an amide bond to create a novel type of MPLA-based fully synthetic glycoconjugate vaccine. 29112822 7 24 from impact 1166:1171 arg1 activity 1212:1219 the immunological activity 1194:1219 the immunological activity of its conjugates 1194:1237 These results revealed not only the self-adjuvant property of MPLA conjugates to elicit robust IgG antibody responses but also the impact of MPLA structure on the immunological activity of its conjugates. 29112822 6 25 theme higher 995:1000 arg1 titers 983:988 antibody titers 974:988 antibody titers much higher 974:1000 Moreover, the 6'-N-conjugate afforded antibody titers much higher than those of the 1-O-conjugate. 29112822 9 26 theme 6'-amino 1428:1435 arg1 derivative 1437:1446 the 6'-amino derivative 1424:1446 the 6'-amino derivative of MPLA 1424:1454 Additionally, the 6'-amino derivative of MPLA was proved to be a useful carrier for the development of fully synthetic carbohydrate-based conjugate vaccines. 29112822 9 26 theme 6'-amino 1428:1435 arg1 carrier 1482:1488 a useful carrier 1473:1488 a useful carrier for the development of fully synthetic carbohydrate-based conjugate vaccines 1473:1565 Additionally, the 6'-amino derivative of MPLA was proved to be a useful carrier for the development of fully synthetic carbohydrate-based conjugate vaccines. 29112822 1 27 theme 6'-OH 213:217 arg1 group 219:223 the 6'-OH group 209:223 the 6'-OH group substituted with an NH2 group 209:253 A monophosphoryl lipid A (MPLA) derivative having the 6'-OH group substituted with an NH2 group was synthesized and coupled with the upstream terminal tetrasaccharide of mycobacterial lipoarabinomannan (LAM) via an amide bond to create a novel type of MPLA-based fully synthetic glycoconjugate vaccine. 29112822 5 28 theme present 883:889 arg1 lymphocytes 871:881 B1 lymphocytes 868:881 B1 lymphocytes present in the intrapleural and peritoneal cavities 868:933 It was thus speculated that MPLA conjugates might act via stimulating B1 lymphocytes present in the intrapleural and peritoneal cavities. 29112822 1 29 theme terminal 301:308 arg1 tetrasaccharide 310:324 the upstream terminal tetrasaccharide 288:324 the upstream terminal tetrasaccharide of mycobacterial lipoarabinomannan (LAM) via an amide bond to create a novel type of MPLA-based fully synthetic glycoconjugate vaccine 288:459 A monophosphoryl lipid A (MPLA) derivative having the 6'-OH group substituted with an NH2 group was synthesized and coupled with the upstream terminal tetrasaccharide of mycobacterial lipoarabinomannan (LAM) via an amide bond to create a novel type of MPLA-based fully synthetic glycoconjugate vaccine. 29112822 8 30 link 6'-N-linked 1310:1320 arg1 conjugates 1287:1296 LAM oligosaccharide-MPLA conjugates 1262:1296 LAM oligosaccharide-MPLA conjugates 1262:1296 It was concluded that LAM oligosaccharide-MPLA conjugates, especially 6'-N-linked, are promising candidates as antituberculosis vaccines worthy of further investigation. 29112822 8 30 link 6'-N-linked 1310:1320 arg1 candidates 1337:1346 promising candidates 1327:1346 promising candidates as antituberculosis vaccines worthy of further investigation 1327:1407 It was concluded that LAM oligosaccharide-MPLA conjugates, especially 6'-N-linked, are promising candidates as antituberculosis vaccines worthy of further investigation. 29112822 7 31 from property 1085:1092 arg1 activity 1212:1219 the immunological activity 1194:1219 the immunological activity of its conjugates 1194:1237 These results revealed not only the self-adjuvant property of MPLA conjugates to elicit robust IgG antibody responses but also the impact of MPLA structure on the immunological activity of its conjugates. 29112822 2 32 theme same 466:469 arg1 tetrasaccharide 471:485 The same tetrasaccharide 462:485 The same tetrasaccharide 462:485 The same tetrasaccharide was also coupled with MPLA at the 1-O-position. 29112822 8 33 theme 6'-N-linked 1310:1320 arg1 conjugates 1287:1296 LAM oligosaccharide-MPLA conjugates 1262:1296 LAM oligosaccharide-MPLA conjugates 1262:1296 It was concluded that LAM oligosaccharide-MPLA conjugates, especially 6'-N-linked, are promising candidates as antituberculosis vaccines worthy of further investigation. 29112822 8 33 theme 6'-N-linked 1310:1320 arg1 candidates 1337:1346 promising candidates 1327:1346 promising candidates as antituberculosis vaccines worthy of further investigation 1327:1407 It was concluded that LAM oligosaccharide-MPLA conjugates, especially 6'-N-linked, are promising candidates as antituberculosis vaccines worthy of further investigation. 29112822 8 34 dep vaccines 1368:1375 arg1 worthy 1377:1382 worthy 1377:1382 antituberculosis vaccines worthy of further investigation 1351:1407 It was concluded that LAM oligosaccharide-MPLA conjugates, especially 6'-N-linked, are promising candidates as antituberculosis vaccines worthy of further investigation. 29112822 5 35 theme intrapleural 898:909 arg1 cavities 926:933 the intrapleural and peritoneal cavities 894:933 the intrapleural and peritoneal cavities 894:933 It was thus speculated that MPLA conjugates might act via stimulating B1 lymphocytes present in the intrapleural and peritoneal cavities. 29112822 0 36 theme Immunological 14:26 arg1 Comparison 28:37 Immunological Comparison 14:37 Immunological Comparison 14:37 Synthesis and Immunological Comparison of Differently Linked Lipoarabinomannan Oligosaccharide-Monophosphoryl Lipid A Conjugates as Antituberculosis Vaccines. 29112822 7 37 theme robust 1123:1128 arg1 responses 1143:1151 robust IgG antibody responses 1123:1151 robust IgG antibody responses 1123:1151 These results revealed not only the self-adjuvant property of MPLA conjugates to elicit robust IgG antibody responses but also the impact of MPLA structure on the immunological activity of its conjugates. 29112822 4 38 theme antibody 666:673 arg1 responses 675:683 robust overall and IgG antibody responses 643:683 responses 675:683 Both afforded robust overall and IgG antibody responses, but intraperitoneal injection elicited responses significantly stronger than those from subcutaneous injection. 29112822 7 39 theme conjugates 1228:1237 arg1 activity 1212:1219 the immunological activity 1194:1219 the immunological activity of its conjugates 1194:1237 These results revealed not only the self-adjuvant property of MPLA conjugates to elicit robust IgG antibody responses but also the impact of MPLA structure on the immunological activity of its conjugates. 29112822 1 40 theme mycobacterial 329:341 arg1 LAM 362:364 LAM 362:364 LAM 362:364 A monophosphoryl lipid A (MPLA) derivative having the 6'-OH group substituted with an NH2 group was synthesized and coupled with the upstream terminal tetrasaccharide of mycobacterial lipoarabinomannan (LAM) via an amide bond to create a novel type of MPLA-based fully synthetic glycoconjugate vaccine. 29112822 1 40 theme mycobacterial 329:341 arg1 lipoarabinomannan 343:359 mycobacterial lipoarabinomannan 329:359 mycobacterial lipoarabinomannan (LAM) via an amide bond to create a novel type of MPLA-based fully synthetic glycoconjugate vaccine 329:459 A monophosphoryl lipid A (MPLA) derivative having the 6'-OH group substituted with an NH2 group was synthesized and coupled with the upstream terminal tetrasaccharide of mycobacterial lipoarabinomannan (LAM) via an amide bond to create a novel type of MPLA-based fully synthetic glycoconjugate vaccine. 29112822 8 41 theme further 1387:1393 arg1 investigation 1395:1407 further investigation 1387:1407 further investigation 1387:1407 It was concluded that LAM oligosaccharide-MPLA conjugates, especially 6'-N-linked, are promising candidates as antituberculosis vaccines worthy of further investigation. 29112822 5 42 theme peritoneal 915:924 arg1 cavities 926:933 the intrapleural and peritoneal cavities 894:933 the intrapleural and peritoneal cavities 894:933 It was thus speculated that MPLA conjugates might act via stimulating B1 lymphocytes present in the intrapleural and peritoneal cavities. 29112822 1 43 theme lipoarabinomannan 343:359 arg1 tetrasaccharide 310:324 the upstream terminal tetrasaccharide 288:324 the upstream terminal tetrasaccharide of mycobacterial lipoarabinomannan (LAM) via an amide bond to create a novel type of MPLA-based fully synthetic glycoconjugate vaccine 288:459 A monophosphoryl lipid A (MPLA) derivative having the 6'-OH group substituted with an NH2 group was synthesized and coupled with the upstream terminal tetrasaccharide of mycobacterial lipoarabinomannan (LAM) via an amide bond to create a novel type of MPLA-based fully synthetic glycoconjugate vaccine. 29112822 1 44 theme MPLA-based 411:420 arg1 vaccine 453:459 MPLA-based fully synthetic glycoconjugate vaccine 411:459 MPLA-based fully synthetic glycoconjugate vaccine 411:459 A monophosphoryl lipid A (MPLA) derivative having the 6'-OH group substituted with an NH2 group was synthesized and coupled with the upstream terminal tetrasaccharide of mycobacterial lipoarabinomannan (LAM) via an amide bond to create a novel type of MPLA-based fully synthetic glycoconjugate vaccine. 29112822 7 45 theme conjugates 1102:1111 arg1 impact 1166:1171 the impact 1162:1171 not only the self-adjuvant property of MPLA conjugates to elicit robust IgG antibody responses but also the impact of MPLA structure on the immunological activity of its conjugates 1058:1237 These results revealed not only the self-adjuvant property of MPLA conjugates to elicit robust IgG antibody responses but also the impact of MPLA structure on the immunological activity of its conjugates. 29112822 7 45 theme conjugates 1102:1111 arg1 property 1085:1092 the self-adjuvant property 1067:1092 not only the self-adjuvant property of MPLA conjugates to elicit robust IgG antibody responses but also the impact of MPLA structure on the immunological activity of its conjugates 1058:1237 These results revealed not only the self-adjuvant property of MPLA conjugates to elicit robust IgG antibody responses but also the impact of MPLA structure on the immunological activity of its conjugates. 29112822 1 46 theme NH2 245:247 arg1 group 249:253 an NH2 group 242:253 an NH2 group 242:253 A monophosphoryl lipid A (MPLA) derivative having the 6'-OH group substituted with an NH2 group was synthesized and coupled with the upstream terminal tetrasaccharide of mycobacterial lipoarabinomannan (LAM) via an amide bond to create a novel type of MPLA-based fully synthetic glycoconjugate vaccine. 29112822 0 47 theme Lipoarabinomannan 61:77 arg1 A 116:116 Differently Linked Lipoarabinomannan Oligosaccharide-Monophosphoryl Lipid A 42:116 Differently Linked Lipoarabinomannan Oligosaccharide-Monophosphoryl Lipid A 42:116 Synthesis and Immunological Comparison of Differently Linked Lipoarabinomannan Oligosaccharide-Monophosphoryl Lipid A Conjugates as Antituberculosis Vaccines. 29112822 7 48 theme IgG 1130:1132 arg1 responses 1143:1151 robust IgG antibody responses 1123:1151 robust IgG antibody responses 1123:1151 These results revealed not only the self-adjuvant property of MPLA conjugates to elicit robust IgG antibody responses but also the impact of MPLA structure on the immunological activity of its conjugates. 29112822 1 49 contain having 202:207 arg2 group 219:223 the 6'-OH group 209:223 the 6'-OH group substituted with an NH2 group 209:253 A monophosphoryl lipid A (MPLA) derivative having the 6'-OH group substituted with an NH2 group was synthesized and coupled with the upstream terminal tetrasaccharide of mycobacterial lipoarabinomannan (LAM) via an amide bond to create a novel type of MPLA-based fully synthetic glycoconjugate vaccine. 29112822 1 49 contain having 202:207 arg1 derivative 191:200 A monophosphoryl lipid A (MPLA) derivative 159:200 A monophosphoryl lipid A (MPLA) derivative having the 6'-OH group substituted with an NH2 group 159:253 A monophosphoryl lipid A (MPLA) derivative having the 6'-OH group substituted with an NH2 group was synthesized and coupled with the upstream terminal tetrasaccharide of mycobacterial lipoarabinomannan (LAM) via an amide bond to create a novel type of MPLA-based fully synthetic glycoconjugate vaccine. 29112822 5 50 from cavities 926:933 arg1 present 883:889 present 883:889 present 883:889 It was thus speculated that MPLA conjugates might act via stimulating B1 lymphocytes present in the intrapleural and peritoneal cavities. 29112822 4 51 theme subcutaneous 774:785 arg1 injection 787:795 subcutaneous injection 774:795 subcutaneous injection 774:795 Both afforded robust overall and IgG antibody responses, but intraperitoneal injection elicited responses significantly stronger than those from subcutaneous injection. 29112822 0 52 theme Linked 54:59 arg1 A 116:116 Differently Linked Lipoarabinomannan Oligosaccharide-Monophosphoryl Lipid A 42:116 Differently Linked Lipoarabinomannan Oligosaccharide-Monophosphoryl Lipid A 42:116 Synthesis and Immunological Comparison of Differently Linked Lipoarabinomannan Oligosaccharide-Monophosphoryl Lipid A Conjugates as Antituberculosis Vaccines. 29112822 9 53 theme useful 1475:1480 arg1 derivative 1437:1446 the 6'-amino derivative 1424:1446 the 6'-amino derivative of MPLA 1424:1454 Additionally, the 6'-amino derivative of MPLA was proved to be a useful carrier for the development of fully synthetic carbohydrate-based conjugate vaccines. 29112822 9 53 theme useful 1475:1480 arg1 carrier 1482:1488 a useful carrier 1473:1488 a useful carrier for the development of fully synthetic carbohydrate-based conjugate vaccines 1473:1565 Additionally, the 6'-amino derivative of MPLA was proved to be a useful carrier for the development of fully synthetic carbohydrate-based conjugate vaccines. 29112822 7 54 theme antibody 1134:1141 arg1 responses 1143:1151 robust IgG antibody responses 1123:1151 robust IgG antibody responses 1123:1151 These results revealed not only the self-adjuvant property of MPLA conjugates to elicit robust IgG antibody responses but also the impact of MPLA structure on the immunological activity of its conjugates. 29112822 1 55 theme synthetic 428:436 arg1 vaccine 453:459 MPLA-based fully synthetic glycoconjugate vaccine 411:459 MPLA-based fully synthetic glycoconjugate vaccine 411:459 A monophosphoryl lipid A (MPLA) derivative having the 6'-OH group substituted with an NH2 group was synthesized and coupled with the upstream terminal tetrasaccharide of mycobacterial lipoarabinomannan (LAM) via an amide bond to create a novel type of MPLA-based fully synthetic glycoconjugate vaccine. 29112822 1 56 theme monophosphoryl 161:174 arg1 MPLA 185:188 MPLA 185:188 MPLA 185:188 A monophosphoryl lipid A (MPLA) derivative having the 6'-OH group substituted with an NH2 group was synthesized and coupled with the upstream terminal tetrasaccharide of mycobacterial lipoarabinomannan (LAM) via an amide bond to create a novel type of MPLA-based fully synthetic glycoconjugate vaccine. 29112822 1 56 theme monophosphoryl 161:174 arg1 A 182:182 monophosphoryl lipid A 161:182 A monophosphoryl lipid A (MPLA) derivative having the 6'-OH group substituted with an NH2 group 159:253 A monophosphoryl lipid A (MPLA) derivative having the 6'-OH group substituted with an NH2 group was synthesized and coupled with the upstream terminal tetrasaccharide of mycobacterial lipoarabinomannan (LAM) via an amide bond to create a novel type of MPLA-based fully synthetic glycoconjugate vaccine. 29112822 1 57 theme glycoconjugate 438:451 arg1 vaccine 453:459 MPLA-based fully synthetic glycoconjugate vaccine 411:459 MPLA-based fully synthetic glycoconjugate vaccine 411:459 A monophosphoryl lipid A (MPLA) derivative having the 6'-OH group substituted with an NH2 group was synthesized and coupled with the upstream terminal tetrasaccharide of mycobacterial lipoarabinomannan (LAM) via an amide bond to create a novel type of MPLA-based fully synthetic glycoconjugate vaccine. 29112822 5 58 theme MPLA 826:829 arg1 conjugates 831:840 MPLA conjugates 826:840 MPLA conjugates 826:840 It was thus speculated that MPLA conjugates might act via stimulating B1 lymphocytes present in the intrapleural and peritoneal cavities. 29112822 1 59 theme lipid 176:180 arg1 MPLA 185:188 MPLA 185:188 MPLA 185:188 A monophosphoryl lipid A (MPLA) derivative having the 6'-OH group substituted with an NH2 group was synthesized and coupled with the upstream terminal tetrasaccharide of mycobacterial lipoarabinomannan (LAM) via an amide bond to create a novel type of MPLA-based fully synthetic glycoconjugate vaccine. 29112822 1 59 theme lipid 176:180 arg1 A 182:182 monophosphoryl lipid A 161:182 A monophosphoryl lipid A (MPLA) derivative having the 6'-OH group substituted with an NH2 group 159:253 A monophosphoryl lipid A (MPLA) derivative having the 6'-OH group substituted with an NH2 group was synthesized and coupled with the upstream terminal tetrasaccharide of mycobacterial lipoarabinomannan (LAM) via an amide bond to create a novel type of MPLA-based fully synthetic glycoconjugate vaccine. 29112822 7 60 theme MPLA 1097:1100 arg1 conjugates 1102:1111 MPLA conjugates 1097:1111 MPLA conjugates 1097:1111 These results revealed not only the self-adjuvant property of MPLA conjugates to elicit robust IgG antibody responses but also the impact of MPLA structure on the immunological activity of its conjugates. 29112822 1 61 theme vaccine 453:459 arg1 type 403:406 a novel type 395:406 a novel type of MPLA-based fully synthetic glycoconjugate vaccine 395:459 A monophosphoryl lipid A (MPLA) derivative having the 6'-OH group substituted with an NH2 group was synthesized and coupled with the upstream terminal tetrasaccharide of mycobacterial lipoarabinomannan (LAM) via an amide bond to create a novel type of MPLA-based fully synthetic glycoconjugate vaccine. 29112822 8 62 theme LAM 1262:1264 arg1 conjugates 1287:1296 LAM oligosaccharide-MPLA conjugates 1262:1296 LAM oligosaccharide-MPLA conjugates 1262:1296 It was concluded that LAM oligosaccharide-MPLA conjugates, especially 6'-N-linked, are promising candidates as antituberculosis vaccines worthy of further investigation. 29112822 8 62 theme LAM 1262:1264 arg1 candidates 1337:1346 promising candidates 1327:1346 promising candidates as antituberculosis vaccines worthy of further investigation 1327:1407 It was concluded that LAM oligosaccharide-MPLA conjugates, especially 6'-N-linked, are promising candidates as antituberculosis vaccines worthy of further investigation. 29112822 7 63 theme self-adjuvant 1071:1083 arg1 property 1085:1092 the self-adjuvant property 1067:1092 not only the self-adjuvant property of MPLA conjugates to elicit robust IgG antibody responses but also the impact of MPLA structure on the immunological activity of its conjugates 1058:1237 These results revealed not only the self-adjuvant property of MPLA conjugates to elicit robust IgG antibody responses but also the impact of MPLA structure on the immunological activity of its conjugates. 29112822 1 64 theme A 182:182 arg1 derivative 191:200 A monophosphoryl lipid A (MPLA) derivative 159:200 A monophosphoryl lipid A (MPLA) derivative having the 6'-OH group substituted with an NH2 group 159:253 A monophosphoryl lipid A (MPLA) derivative having the 6'-OH group substituted with an NH2 group was synthesized and coupled with the upstream terminal tetrasaccharide of mycobacterial lipoarabinomannan (LAM) via an amide bond to create a novel type of MPLA-based fully synthetic glycoconjugate vaccine. 29112822 0 65 theme Lipid 110:114 arg1 A 116:116 Differently Linked Lipoarabinomannan Oligosaccharide-Monophosphoryl Lipid A 42:116 Differently Linked Lipoarabinomannan Oligosaccharide-Monophosphoryl Lipid A 42:116 Synthesis and Immunological Comparison of Differently Linked Lipoarabinomannan Oligosaccharide-Monophosphoryl Lipid A Conjugates as Antituberculosis Vaccines. 29112822 4 66 theme stronger 749:756 arg1 responses 725:733 responses 725:733 responses significantly stronger than those from subcutaneous injection 725:795 Both afforded robust overall and IgG antibody responses, but intraperitoneal injection elicited responses significantly stronger than those from subcutaneous injection. 29112822 8 67 theme promising 1327:1335 arg1 conjugates 1287:1296 LAM oligosaccharide-MPLA conjugates 1262:1296 LAM oligosaccharide-MPLA conjugates 1262:1296 It was concluded that LAM oligosaccharide-MPLA conjugates, especially 6'-N-linked, are promising candidates as antituberculosis vaccines worthy of further investigation. 29112822 8 67 theme promising 1327:1335 arg1 candidates 1337:1346 promising candidates 1327:1346 promising candidates as antituberculosis vaccines worthy of further investigation 1327:1407 It was concluded that LAM oligosaccharide-MPLA conjugates, especially 6'-N-linked, are promising candidates as antituberculosis vaccines worthy of further investigation. 29112822 4 68 theme IgG 662:664 arg1 responses 675:683 robust overall and IgG antibody responses 643:683 responses 675:683 Both afforded robust overall and IgG antibody responses, but intraperitoneal injection elicited responses significantly stronger than those from subcutaneous injection. 29112822 0 69 theme Oligosaccharide-Monophosphoryl 79:108 arg1 A 116:116 Differently Linked Lipoarabinomannan Oligosaccharide-Monophosphoryl Lipid A 42:116 Differently Linked Lipoarabinomannan Oligosaccharide-Monophosphoryl Lipid A 42:116 Synthesis and Immunological Comparison of Differently Linked Lipoarabinomannan Oligosaccharide-Monophosphoryl Lipid A Conjugates as Antituberculosis Vaccines. 28940310 8 0 theme deleterious 1111:1121 arg1 consequences 1134:1145 deleterious functional consequences 1111:1145 deleterious functional consequences 1111:1145 These are missense and nonsense mutations with deleterious functional consequences. 28940310 9 1 from world 1251:1255 arg1 list 1208:1211 a list 1206:1211 a list of reported CDG mutations in the Arab world 1206:1255 This article integrates a single-center experience within a list of reported CDG mutations in the Arab world, accompanied by full molecular and clinical details pertaining to the studied cases. 28940310 3 2 from differences 474:484 arg1 landscape 504:512 the mutational landscape 489:512 the mutational landscape of each of these subgroups 489:539 This is further complicated by ethno-geographic differences in the mutational landscape of each of these subgroups. 28940310 4 3 theme sequencing 729:738 arg1 approaches 701:710 biochemical (glycosylation status of transferrin) and molecular approaches 637:710 biochemical (glycosylation status of transferrin) and molecular approaches (next-generation sequencing [NGS] 637:744 Ten Arab CDG patients from Latifa Hospital in Dubai, United Arab Emirates, were assessed using biochemical (glycosylation status of transferrin) and molecular approaches (next-generation sequencing [NGS] and Sanger sequencing). 28940310 4 3 theme sequencing 729:738 arg1 [NGS 740:743 next-generation sequencing [NGS 713:743 next-generation sequencing [NGS 713:743 Ten Arab CDG patients from Latifa Hospital in Dubai, United Arab Emirates, were assessed using biochemical (glycosylation status of transferrin) and molecular approaches (next-generation sequencing [NGS] and Sanger sequencing). 28940310 5 4 theme In 770:771 arg1 tools 780:784 In silico tools 770:784 In silico tools including CADD and PolyPhen-2 770:814 In silico tools including CADD and PolyPhen-2 were used to predict the functional consequences of uncovered mutations. 28940310 5 4 theme In 770:771 arg1 PolyPhen-2 805:814 PolyPhen-2 805:814 PolyPhen-2 805:814 In silico tools including CADD and PolyPhen-2 were used to predict the functional consequences of uncovered mutations. 28940310 5 4 theme In 770:771 arg1 CADD 796:799 CADD 796:799 CADD 796:799 In silico tools including CADD and PolyPhen-2 were used to predict the functional consequences of uncovered mutations. 28940310 4 5 theme Arab 546:549 arg1 patients 555:562 Ten Arab CDG patients 542:562 Ten Arab CDG patients from Latifa Hospital in Dubai, United Arab Emirates, 542:615 Ten Arab CDG patients from Latifa Hospital in Dubai, United Arab Emirates, were assessed using biochemical (glycosylation status of transferrin) and molecular approaches (next-generation sequencing [NGS] and Sanger sequencing). 28940310 0 6 link N-linked 28:35 arg1 Disorders 48:56 N-linked Congenital Disorders 28:56 N-linked Congenital Disorders of Glycosylation 28:73 Single-center experience of N-linked Congenital Disorders of Glycosylation with a Summary of Molecularly Characterized Cases in Arabs. 28940310 4 7 theme next-generation 713:727 arg1 approaches 701:710 biochemical (glycosylation status of transferrin) and molecular approaches 637:710 biochemical (glycosylation status of transferrin) and molecular approaches (next-generation sequencing [NGS] 637:744 Ten Arab CDG patients from Latifa Hospital in Dubai, United Arab Emirates, were assessed using biochemical (glycosylation status of transferrin) and molecular approaches (next-generation sequencing [NGS] and Sanger sequencing). 28940310 4 7 theme next-generation 713:727 arg1 [NGS 740:743 next-generation sequencing [NGS 713:743 next-generation sequencing [NGS 713:743 Ten Arab CDG patients from Latifa Hospital in Dubai, United Arab Emirates, were assessed using biochemical (glycosylation status of transferrin) and molecular approaches (next-generation sequencing [NGS] and Sanger sequencing). 28940310 0 8 theme Characterized 105:117 arg1 Cases 119:123 Molecularly Characterized Cases 93:123 Molecularly Characterized Cases in Arabs 93:132 Single-center experience of N-linked Congenital Disorders of Glycosylation with a Summary of Molecularly Characterized Cases in Arabs. 28940310 6 9 theme novel 921:925 arg1 mutations 927:935 five novel mutations 916:935 five novel mutations 916:935 In our sample of patients, five novel mutations were uncovered in the genes: MPDU1, PMM2, MAN1B1, and RFT1. 28940310 1 10 theme lipid 262:266 arg1 glycosylation 268:280 lipid glycosylation 262:280 lipid glycosylation 262:280 Congenital disorders of glycosylation (CDG) represent an expanding group of conditions that result from defects in protein and lipid glycosylation. 28940310 8 11 theme functional 1123:1132 arg1 consequences 1134:1145 deleterious functional consequences 1111:1145 deleterious functional consequences 1111:1145 These are missense and nonsense mutations with deleterious functional consequences. 28940310 9 12 theme molecular 1278:1286 arg1 details 1301:1307 full molecular and clinical details 1273:1307 full molecular and clinical details pertaining to the studied cases 1273:1339 This article integrates a single-center experience within a list of reported CDG mutations in the Arab world, accompanied by full molecular and clinical details pertaining to the studied cases. 28940310 8 13 with mutations 1096:1104 arg1 consequences 1134:1145 deleterious functional consequences 1111:1145 deleterious functional consequences 1111:1145 These are missense and nonsense mutations with deleterious functional consequences. 28940310 4 14 theme Sanger 750:755 arg1 sequencing 757:766 Sanger sequencing) 750:767 Sanger sequencing) 750:767 Ten Arab CDG patients from Latifa Hospital in Dubai, United Arab Emirates, were assessed using biochemical (glycosylation status of transferrin) and molecular approaches (next-generation sequencing [NGS] and Sanger sequencing). 28940310 5 15 theme uncovered 868:876 arg1 mutations 878:886 uncovered mutations 868:886 uncovered mutations 868:886 In silico tools including CADD and PolyPhen-2 were used to predict the functional consequences of uncovered mutations. 28940310 2 16 theme Different 283:291 arg1 subgroups 293:301 Different subgroups 283:301 Different subgroups of CDG 283:308 Different subgroups of CDG display considerable clinical and genetic heterogeneity due to the highly complex nature of cellular glycosylation. 28940310 2 17 theme glycosylation 411:423 arg1 nature 392:397 the highly complex nature 373:397 the highly complex nature of cellular glycosylation 373:423 Different subgroups of CDG display considerable clinical and genetic heterogeneity due to the highly complex nature of cellular glycosylation. 28940310 0 18 theme Cases 119:123 arg1 Summary 82:88 a Summary 80:88 a Summary of Molecularly Characterized Cases in Arabs 80:132 Single-center experience of N-linked Congenital Disorders of Glycosylation with a Summary of Molecularly Characterized Cases in Arabs. 28940310 6 19 theme patients 906:913 arg1 sample 896:901 our sample 892:901 our sample of patients 892:913 In our sample of patients, five novel mutations were uncovered in the genes: MPDU1, PMM2, MAN1B1, and RFT1. 28940310 4 20 gly glycosylation 650:662 arg1 transferrin 674:684 transferrin 674:684 transferrin 674:684 Ten Arab CDG patients from Latifa Hospital in Dubai, United Arab Emirates, were assessed using biochemical (glycosylation status of transferrin) and molecular approaches (next-generation sequencing [NGS] and Sanger sequencing). 28940310 9 21 theme reported 1216:1223 arg1 mutations 1229:1237 reported CDG mutations 1216:1237 reported CDG mutations in the Arab world 1216:1255 This article integrates a single-center experience within a list of reported CDG mutations in the Arab world, accompanied by full molecular and clinical details pertaining to the studied cases. 28940310 7 22 from patients 1043:1050 arg1 genes 1057:1061 7 genes 1055:1061 7 genes 1055:1061 In total, 9 mutations were harbored by the 10 patients in 7 genes. 28940310 2 23 theme cellular 402:409 arg1 glycosylation 411:423 cellular glycosylation 402:423 cellular glycosylation 402:423 Different subgroups of CDG display considerable clinical and genetic heterogeneity due to the highly complex nature of cellular glycosylation. 28940310 2 24 theme clinical 331:338 arg1 heterogeneity 352:364 considerable clinical and genetic heterogeneity 318:364 considerable clinical and genetic heterogeneity due to the highly complex nature of cellular glycosylation 318:423 Different subgroups of CDG display considerable clinical and genetic heterogeneity due to the highly complex nature of cellular glycosylation. 28940310 4 25 theme molecular 691:699 arg1 approaches 701:710 biochemical (glycosylation status of transferrin) and molecular approaches 637:710 biochemical (glycosylation status of transferrin) and molecular approaches (next-generation sequencing [NGS] 637:744 Ten Arab CDG patients from Latifa Hospital in Dubai, United Arab Emirates, were assessed using biochemical (glycosylation status of transferrin) and molecular approaches (next-generation sequencing [NGS] and Sanger sequencing). 28940310 4 25 theme molecular 691:699 arg1 [NGS 740:743 next-generation sequencing [NGS 713:743 next-generation sequencing [NGS 713:743 Ten Arab CDG patients from Latifa Hospital in Dubai, United Arab Emirates, were assessed using biochemical (glycosylation status of transferrin) and molecular approaches (next-generation sequencing [NGS] and Sanger sequencing). 28940310 2 26 theme considerable 318:329 arg1 heterogeneity 352:364 considerable clinical and genetic heterogeneity 318:364 considerable clinical and genetic heterogeneity due to the highly complex nature of cellular glycosylation 318:423 Different subgroups of CDG display considerable clinical and genetic heterogeneity due to the highly complex nature of cellular glycosylation. 28940310 1 27 theme expanding 192:200 arg1 conditions 211:220 conditions 211:220 conditions that result from defects in protein and lipid glycosylation 211:280 Congenital disorders of glycosylation (CDG) represent an expanding group of conditions that result from defects in protein and lipid glycosylation. 28940310 1 27 theme expanding 192:200 arg1 group 202:206 an expanding group 189:206 an expanding group of conditions that result from defects in protein and lipid glycosylation 189:280 Congenital disorders of glycosylation (CDG) represent an expanding group of conditions that result from defects in protein and lipid glycosylation. 28940310 0 28 theme N-linked 28:35 arg1 Disorders 48:56 N-linked Congenital Disorders 28:56 N-linked Congenital Disorders of Glycosylation 28:73 Single-center experience of N-linked Congenital Disorders of Glycosylation with a Summary of Molecularly Characterized Cases in Arabs. 28940310 5 29 used used 821:824 arg2 CADD 796:799 CADD 796:799 CADD 796:799 In silico tools including CADD and PolyPhen-2 were used to predict the functional consequences of uncovered mutations. 28940310 5 29 used used 821:824 arg2 tools 780:784 In silico tools 770:784 In silico tools including CADD and PolyPhen-2 770:814 In silico tools including CADD and PolyPhen-2 were used to predict the functional consequences of uncovered mutations. 28940310 5 29 used used 821:824 arg2 PolyPhen-2 805:814 PolyPhen-2 805:814 PolyPhen-2 805:814 In silico tools including CADD and PolyPhen-2 were used to predict the functional consequences of uncovered mutations. 28940310 10 30 theme ethnic 1375:1380 arg1 differences 1382:1392 potential ethnic differences 1365:1392 potential ethnic differences that were not noted before in regards to CDG in the Arab world 1365:1455 It also sheds light on potential ethnic differences that were not noted before in regards to CDG in the Arab world. 28940310 10 31 theme potential 1365:1373 arg1 differences 1382:1392 potential ethnic differences 1365:1392 potential ethnic differences that were not noted before in regards to CDG in the Arab world 1365:1455 It also sheds light on potential ethnic differences that were not noted before in regards to CDG in the Arab world. 28940310 3 32 theme mutational 493:502 arg1 landscape 504:512 the mutational landscape 489:512 the mutational landscape of each of these subgroups 489:539 This is further complicated by ethno-geographic differences in the mutational landscape of each of these subgroups. 28940310 4 33 from Hospital 576:583 arg1 patients 555:562 Ten Arab CDG patients 542:562 Ten Arab CDG patients from Latifa Hospital in Dubai, United Arab Emirates, 542:615 Ten Arab CDG patients from Latifa Hospital in Dubai, United Arab Emirates, were assessed using biochemical (glycosylation status of transferrin) and molecular approaches (next-generation sequencing [NGS] and Sanger sequencing). 28940310 9 34 theme mutations 1229:1237 arg1 list 1208:1211 a list 1206:1211 a list of reported CDG mutations in the Arab world 1206:1255 This article integrates a single-center experience within a list of reported CDG mutations in the Arab world, accompanied by full molecular and clinical details pertaining to the studied cases. 28940310 2 35 theme CDG 306:308 arg1 subgroups 293:301 Different subgroups 283:301 Different subgroups of CDG 283:308 Different subgroups of CDG display considerable clinical and genetic heterogeneity due to the highly complex nature of cellular glycosylation. 28940310 9 36 theme studied 1327:1333 arg1 cases 1335:1339 the studied cases 1323:1339 the studied cases 1323:1339 This article integrates a single-center experience within a list of reported CDG mutations in the Arab world, accompanied by full molecular and clinical details pertaining to the studied cases. 28940310 10 37 theme Arab 1446:1449 arg1 world 1451:1455 the Arab world 1442:1455 the Arab world 1442:1455 It also sheds light on potential ethnic differences that were not noted before in regards to CDG in the Arab world. 28940310 0 38 from Summary 82:88 arg1 Arabs 128:132 Arabs 128:132 Arabs 128:132 Single-center experience of N-linked Congenital Disorders of Glycosylation with a Summary of Molecularly Characterized Cases in Arabs. 28940310 1 39 theme conditions 211:220 arg1 conditions 211:220 conditions 211:220 conditions that result from defects in protein and lipid glycosylation 211:280 Congenital disorders of glycosylation (CDG) represent an expanding group of conditions that result from defects in protein and lipid glycosylation. 28940310 1 39 theme conditions 211:220 arg1 group 202:206 an expanding group 189:206 an expanding group of conditions that result from defects in protein and lipid glycosylation 189:280 Congenital disorders of glycosylation (CDG) represent an expanding group of conditions that result from defects in protein and lipid glycosylation. 28940310 0 40 theme Congenital 37:46 arg1 Disorders 48:56 N-linked Congenital Disorders 28:56 N-linked Congenital Disorders of Glycosylation 28:73 Single-center experience of N-linked Congenital Disorders of Glycosylation with a Summary of Molecularly Characterized Cases in Arabs. 28940310 9 41 theme CDG 1225:1227 arg1 mutations 1229:1237 reported CDG mutations 1216:1237 reported CDG mutations in the Arab world 1216:1255 This article integrates a single-center experience within a list of reported CDG mutations in the Arab world, accompanied by full molecular and clinical details pertaining to the studied cases. 28940310 5 42 theme mutations 878:886 arg1 consequences 852:863 the functional consequences 837:863 the functional consequences of uncovered mutations 837:886 In silico tools including CADD and PolyPhen-2 were used to predict the functional consequences of uncovered mutations. 28940310 0 43 theme Glycosylation 61:73 arg1 Disorders 48:56 N-linked Congenital Disorders 28:56 N-linked Congenital Disorders of Glycosylation 28:73 Single-center experience of N-linked Congenital Disorders of Glycosylation with a Summary of Molecularly Characterized Cases in Arabs. 28940310 4 44 theme CDG 551:553 arg1 patients 555:562 Ten Arab CDG patients 542:562 Ten Arab CDG patients from Latifa Hospital in Dubai, United Arab Emirates, 542:615 Ten Arab CDG patients from Latifa Hospital in Dubai, United Arab Emirates, were assessed using biochemical (glycosylation status of transferrin) and molecular approaches (next-generation sequencing [NGS] and Sanger sequencing). 28940310 1 45 from defects 239:245 arg1 protein 250:256 protein 250:256 protein 250:256 Congenital disorders of glycosylation (CDG) represent an expanding group of conditions that result from defects in protein and lipid glycosylation. 28940310 1 45 from defects 239:245 arg1 glycosylation 268:280 lipid glycosylation 262:280 lipid glycosylation 262:280 Congenital disorders of glycosylation (CDG) represent an expanding group of conditions that result from defects in protein and lipid glycosylation. 28940310 3 46 theme ethno-geographic 457:472 arg1 differences 474:484 ethno-geographic differences 457:484 ethno-geographic differences in the mutational landscape of each of these subgroups 457:539 This is further complicated by ethno-geographic differences in the mutational landscape of each of these subgroups. 28940310 9 47 theme clinical 1292:1299 arg1 details 1301:1307 full molecular and clinical details 1273:1307 full molecular and clinical details pertaining to the studied cases 1273:1339 This article integrates a single-center experience within a list of reported CDG mutations in the Arab world, accompanied by full molecular and clinical details pertaining to the studied cases. 28940310 2 48 theme due 366:368 arg1 heterogeneity 352:364 considerable clinical and genetic heterogeneity 318:364 considerable clinical and genetic heterogeneity due to the highly complex nature of cellular glycosylation 318:423 Different subgroups of CDG display considerable clinical and genetic heterogeneity due to the highly complex nature of cellular glycosylation. 28940310 9 49 theme full 1273:1276 arg1 details 1301:1307 full molecular and clinical details 1273:1307 full molecular and clinical details pertaining to the studied cases 1273:1339 This article integrates a single-center experience within a list of reported CDG mutations in the Arab world, accompanied by full molecular and clinical details pertaining to the studied cases. 28940310 5 50 dep In 770:771 arg1 silico 773:778 silico 773:778 silico 773:778 In silico tools including CADD and PolyPhen-2 were used to predict the functional consequences of uncovered mutations. 28940310 4 51 dep biochemical 637:647 arg1 status 664:669 glycosylation status 650:669 glycosylation status of transferrin 650:684 Ten Arab CDG patients from Latifa Hospital in Dubai, United Arab Emirates, were assessed using biochemical (glycosylation status of transferrin) and molecular approaches (next-generation sequencing [NGS] and Sanger sequencing). 28940310 9 52 from list 1208:1211 arg1 world 1251:1255 the Arab world 1242:1255 the Arab world 1242:1255 This article integrates a single-center experience within a list of reported CDG mutations in the Arab world, accompanied by full molecular and clinical details pertaining to the studied cases. 28940310 9 53 from mutations 1229:1237 arg1 world 1251:1255 the Arab world 1242:1255 the Arab world 1242:1255 This article integrates a single-center experience within a list of reported CDG mutations in the Arab world, accompanied by full molecular and clinical details pertaining to the studied cases. 28940310 0 54 from Cases 119:123 arg1 Arabs 128:132 Arabs 128:132 Arabs 128:132 Single-center experience of N-linked Congenital Disorders of Glycosylation with a Summary of Molecularly Characterized Cases in Arabs. 28940310 1 55 theme Congenital 135:144 arg1 disorders 146:154 Congenital disorders 135:154 Congenital disorders of glycosylation (CDG) 135:177 Congenital disorders of glycosylation (CDG) represent an expanding group of conditions that result from defects in protein and lipid glycosylation. 28940310 9 56 dep single-center 1174:1186 arg1 experience 1188:1197 experience 1188:1197 experience 1188:1197 This article integrates a single-center experience within a list of reported CDG mutations in the Arab world, accompanied by full molecular and clinical details pertaining to the studied cases. 28940310 8 57 theme missense 1074:1081 arg1 mutations 1096:1104 missense and nonsense mutations 1074:1104 mutations 1096:1104 These are missense and nonsense mutations with deleterious functional consequences. 28940310 8 57 theme missense 1074:1081 arg1 These 1064:1068 These 1064:1068 These 1064:1068 These are missense and nonsense mutations with deleterious functional consequences. 28940310 9 58 theme Arab 1246:1249 arg1 world 1251:1255 the Arab world 1242:1255 the Arab world 1242:1255 This article integrates a single-center experience within a list of reported CDG mutations in the Arab world, accompanied by full molecular and clinical details pertaining to the studied cases. 28940310 3 59 theme each 517:520 arg1 landscape 504:512 the mutational landscape 489:512 the mutational landscape of each of these subgroups 489:539 This is further complicated by ethno-geographic differences in the mutational landscape of each of these subgroups. 28940310 2 60 theme genetic 344:350 arg1 heterogeneity 352:364 considerable clinical and genetic heterogeneity 318:364 considerable clinical and genetic heterogeneity due to the highly complex nature of cellular glycosylation 318:423 Different subgroups of CDG display considerable clinical and genetic heterogeneity due to the highly complex nature of cellular glycosylation. 28940310 4 61 theme glycosylation 650:662 arg1 status 664:669 glycosylation status 650:669 glycosylation status of transferrin 650:684 Ten Arab CDG patients from Latifa Hospital in Dubai, United Arab Emirates, were assessed using biochemical (glycosylation status of transferrin) and molecular approaches (next-generation sequencing [NGS] and Sanger sequencing). 28940310 2 62 theme complex 384:390 arg1 nature 392:397 the highly complex nature 373:397 the highly complex nature of cellular glycosylation 373:423 Different subgroups of CDG display considerable clinical and genetic heterogeneity due to the highly complex nature of cellular glycosylation. 28940310 4 63 theme transferrin 674:684 arg1 status 664:669 glycosylation status 650:669 glycosylation status of transferrin 650:684 Ten Arab CDG patients from Latifa Hospital in Dubai, United Arab Emirates, were assessed using biochemical (glycosylation status of transferrin) and molecular approaches (next-generation sequencing [NGS] and Sanger sequencing). 28940310 4 64 theme biochemical 637:647 arg1 approaches 701:710 biochemical (glycosylation status of transferrin) and molecular approaches 637:710 biochemical (glycosylation status of transferrin) and molecular approaches (next-generation sequencing [NGS] 637:744 Ten Arab CDG patients from Latifa Hospital in Dubai, United Arab Emirates, were assessed using biochemical (glycosylation status of transferrin) and molecular approaches (next-generation sequencing [NGS] and Sanger sequencing). 28940310 4 64 theme biochemical 637:647 arg1 [NGS 740:743 next-generation sequencing [NGS 713:743 next-generation sequencing [NGS 713:743 Ten Arab CDG patients from Latifa Hospital in Dubai, United Arab Emirates, were assessed using biochemical (glycosylation status of transferrin) and molecular approaches (next-generation sequencing [NGS] and Sanger sequencing). 28940310 8 65 theme nonsense 1087:1094 arg1 mutations 1096:1104 missense and nonsense mutations 1074:1104 mutations 1096:1104 These are missense and nonsense mutations with deleterious functional consequences. 28940310 8 65 theme nonsense 1087:1094 arg1 These 1064:1068 These 1064:1068 These 1064:1068 These are missense and nonsense mutations with deleterious functional consequences. 28940310 5 66 theme functional 841:850 arg1 consequences 852:863 the functional consequences 837:863 the functional consequences of uncovered mutations 837:886 In silico tools including CADD and PolyPhen-2 were used to predict the functional consequences of uncovered mutations. 28940310 1 67 theme glycosylation 159:171 arg1 disorders 146:154 Congenital disorders 135:154 Congenital disorders of glycosylation (CDG) 135:177 Congenital disorders of glycosylation (CDG) represent an expanding group of conditions that result from defects in protein and lipid glycosylation. 28940310 0 68 from Arabs 128:132 arg1 Summary 82:88 a Summary 80:88 a Summary of Molecularly Characterized Cases in Arabs 80:132 Single-center experience of N-linked Congenital Disorders of Glycosylation with a Summary of Molecularly Characterized Cases in Arabs. 28860277 0 0 theme ER 83:84 arg1 translocon 86:95 the ER translocon 79:95 the ER translocon 79:95 DC2 and KCP2 mediate the interaction between the oligosaccharyltransferase and the ER translocon. 28860277 6 1 theme C-terminal 962:971 arg1 tail 973:976 the C-terminal tail 958:976 the C-terminal tail of DC2 958:983 Deletion mutagenesis revealed that a conserved motif in the C-terminal tail of DC2 is critical for assembly into the STT3A complex, whereas the lumenal loop and the N-terminal cytoplasmic segment are necessary for the functional interaction between the STT3A and Sec61 complexes. 28860277 1 2 theme oligosaccharyltransferase 146:170 arg1 isoform 131:137 the STT3A isoform 121:137 the STT3A isoform of the oligosaccharyltransferase 121:170 In metazoan organisms, the STT3A isoform of the oligosaccharyltransferase is localized adjacent to the protein translocation channel to catalyze co-translational N-linked glycosylation of proteins in the endoplasmic reticulum. 28860277 1 3 link N-linked 260:267 arg1 glycosylation 269:281 co-translational N-linked glycosylation 243:281 co-translational N-linked glycosylation of proteins in the endoplasmic reticulum 243:322 In metazoan organisms, the STT3A isoform of the oligosaccharyltransferase is localized adjacent to the protein translocation channel to catalyze co-translational N-linked glycosylation of proteins in the endoplasmic reticulum. 28860277 2 4 theme STT3A 383:387 arg1 complex 389:395 the STT3A complex 379:395 the STT3A complex 379:395 The mechanism responsible for the interaction between the STT3A complex and the translocation channel has not been addressed. 28860277 3 5 theme DC2 555:557 arg1 loss 547:550 loss 547:550 loss of DC2 547:557 Using genetically modified human cells that are deficient in DC2 or KCP2 proteins, we show that loss of DC2 causes a defect in co-translational N-glycosylation of proteins that mimics an STT3A phenotype. 28860277 1 6 theme proteins 286:293 arg1 glycosylation 269:281 co-translational N-linked glycosylation 243:281 co-translational N-linked glycosylation of proteins in the endoplasmic reticulum 243:322 In metazoan organisms, the STT3A isoform of the oligosaccharyltransferase is localized adjacent to the protein translocation channel to catalyze co-translational N-linked glycosylation of proteins in the endoplasmic reticulum. 28860277 6 7 theme STT3A 1155:1159 arg1 complexes 1171:1179 the STT3A and Sec61 complexes 1151:1179 complexes 1171:1179 Deletion mutagenesis revealed that a conserved motif in the C-terminal tail of DC2 is critical for assembly into the STT3A complex, whereas the lumenal loop and the N-terminal cytoplasmic segment are necessary for the functional interaction between the STT3A and Sec61 complexes. 28860277 6 8 from motif 949:953 arg1 tail 973:976 the C-terminal tail 958:976 the C-terminal tail of DC2 958:983 Deletion mutagenesis revealed that a conserved motif in the C-terminal tail of DC2 is critical for assembly into the STT3A complex, whereas the lumenal loop and the N-terminal cytoplasmic segment are necessary for the functional interaction between the STT3A and Sec61 complexes. 28860277 4 9 theme protein 759:765 arg1 channel 781:787 the protein translocation channel 755:787 the protein translocation channel 755:787 Biochemical analysis showed that DC2 and KCP2 are responsible for mediating the interaction between the protein translocation channel and the STT3A complex. 28860277 1 10 from reticulum 314:322 arg1 glycosylation 269:281 co-translational N-linked glycosylation 243:281 co-translational N-linked glycosylation of proteins in the endoplasmic reticulum 243:322 In metazoan organisms, the STT3A isoform of the oligosaccharyltransferase is localized adjacent to the protein translocation channel to catalyze co-translational N-linked glycosylation of proteins in the endoplasmic reticulum. 28860277 6 11 theme cytoplasmic 1078:1088 arg1 necessary 1102:1110 necessary 1102:1110 necessary 1102:1110 Deletion mutagenesis revealed that a conserved motif in the C-terminal tail of DC2 is critical for assembly into the STT3A complex, whereas the lumenal loop and the N-terminal cytoplasmic segment are necessary for the functional interaction between the STT3A and Sec61 complexes. 28860277 6 11 theme cytoplasmic 1078:1088 arg1 segment 1090:1096 the N-terminal cytoplasmic segment 1063:1096 the N-terminal cytoplasmic segment 1063:1096 Deletion mutagenesis revealed that a conserved motif in the C-terminal tail of DC2 is critical for assembly into the STT3A complex, whereas the lumenal loop and the N-terminal cytoplasmic segment are necessary for the functional interaction between the STT3A and Sec61 complexes. 28860277 3 12 theme human 478:482 arg1 cells 484:488 genetically modified human cells 457:488 genetically modified human cells that are deficient in DC2 or KCP2 proteins 457:531 Using genetically modified human cells that are deficient in DC2 or KCP2 proteins, we show that loss of DC2 causes a defect in co-translational N-glycosylation of proteins that mimics an STT3A phenotype. 28860277 6 13 theme STT3A 1019:1023 arg1 complex 1025:1031 the STT3A complex 1015:1031 the STT3A complex 1015:1031 Deletion mutagenesis revealed that a conserved motif in the C-terminal tail of DC2 is critical for assembly into the STT3A complex, whereas the lumenal loop and the N-terminal cytoplasmic segment are necessary for the functional interaction between the STT3A and Sec61 complexes. 28860277 3 14 from DC2 512:514 arg1 deficient 499:507 deficient 499:507 deficient 499:507 Using genetically modified human cells that are deficient in DC2 or KCP2 proteins, we show that loss of DC2 causes a defect in co-translational N-glycosylation of proteins that mimics an STT3A phenotype. 28860277 6 15 theme functional 1120:1129 arg1 interaction 1131:1141 the functional interaction 1116:1141 the functional interaction between the STT3A and Sec61 complexes 1116:1179 Deletion mutagenesis revealed that a conserved motif in the C-terminal tail of DC2 is critical for assembly into the STT3A complex, whereas the lumenal loop and the N-terminal cytoplasmic segment are necessary for the functional interaction between the STT3A and Sec61 complexes. 28860277 5 16 theme KCP2-deficient 834:847 arg1 complexes 855:863 DC2- and KCP2-deficient STT3A complexes 825:863 DC2- and KCP2-deficient STT3A complexes 825:863 Importantly, DC2- and KCP2-deficient STT3A complexes are stable and enzymatically active. 28860277 1 17 gly glycosylation 269:281 arg1 proteins 286:293 proteins 286:293 proteins in the endoplasmic reticulum 286:322 In metazoan organisms, the STT3A isoform of the oligosaccharyltransferase is localized adjacent to the protein translocation channel to catalyze co-translational N-linked glycosylation of proteins in the endoplasmic reticulum. 28860277 4 18 theme translocation 767:779 arg1 channel 781:787 the protein translocation channel 755:787 the protein translocation channel 755:787 Biochemical analysis showed that DC2 and KCP2 are responsible for mediating the interaction between the protein translocation channel and the STT3A complex. 28860277 6 19 theme conserved 939:947 arg1 critical 988:995 critical 988:995 critical 988:995 Deletion mutagenesis revealed that a conserved motif in the C-terminal tail of DC2 is critical for assembly into the STT3A complex, whereas the lumenal loop and the N-terminal cytoplasmic segment are necessary for the functional interaction between the STT3A and Sec61 complexes. 28860277 6 19 theme conserved 939:947 arg1 motif 949:953 a conserved motif 937:953 a conserved motif in the C-terminal tail of DC2 937:983 Deletion mutagenesis revealed that a conserved motif in the C-terminal tail of DC2 is critical for assembly into the STT3A complex, whereas the lumenal loop and the N-terminal cytoplasmic segment are necessary for the functional interaction between the STT3A and Sec61 complexes. 28860277 5 20 theme STT3A 849:853 arg1 complexes 855:863 DC2- and KCP2-deficient STT3A complexes 825:863 DC2- and KCP2-deficient STT3A complexes 825:863 Importantly, DC2- and KCP2-deficient STT3A complexes are stable and enzymatically active. 28860277 2 21 theme responsible 339:349 arg1 mechanism 329:337 The mechanism 325:337 The mechanism responsible for the interaction between the STT3A complex and the translocation channel 325:425 The mechanism responsible for the interaction between the STT3A complex and the translocation channel has not been addressed. 28860277 2 22 theme translocation 405:417 arg1 channel 419:425 the translocation channel 401:425 the translocation channel 401:425 The mechanism responsible for the interaction between the STT3A complex and the translocation channel has not been addressed. 28860277 1 23 theme endoplasmic 302:312 arg1 reticulum 314:322 the endoplasmic reticulum 298:322 the endoplasmic reticulum 298:322 In metazoan organisms, the STT3A isoform of the oligosaccharyltransferase is localized adjacent to the protein translocation channel to catalyze co-translational N-linked glycosylation of proteins in the endoplasmic reticulum. 28860277 1 24 from proteins 286:293 arg1 reticulum 314:322 the endoplasmic reticulum 298:322 the endoplasmic reticulum 298:322 In metazoan organisms, the STT3A isoform of the oligosaccharyltransferase is localized adjacent to the protein translocation channel to catalyze co-translational N-linked glycosylation of proteins in the endoplasmic reticulum. 28860277 3 25 from proteins 524:531 arg1 deficient 499:507 deficient 499:507 deficient 499:507 Using genetically modified human cells that are deficient in DC2 or KCP2 proteins, we show that loss of DC2 causes a defect in co-translational N-glycosylation of proteins that mimics an STT3A phenotype. 28860277 4 26 theme Biochemical 655:665 arg1 analysis 667:674 Biochemical analysis 655:674 Biochemical analysis 655:674 Biochemical analysis showed that DC2 and KCP2 are responsible for mediating the interaction between the protein translocation channel and the STT3A complex. 28860277 3 27 theme co-translational 578:593 arg1 N-glycosylation 595:609 co-translational N-glycosylation 578:609 co-translational N-glycosylation of proteins that mimics an STT3A phenotype 578:652 Using genetically modified human cells that are deficient in DC2 or KCP2 proteins, we show that loss of DC2 causes a defect in co-translational N-glycosylation of proteins that mimics an STT3A phenotype. 28860277 1 28 theme metazoan 101:108 arg1 organisms 110:118 metazoan organisms 101:118 metazoan organisms 101:118 In metazoan organisms, the STT3A isoform of the oligosaccharyltransferase is localized adjacent to the protein translocation channel to catalyze co-translational N-linked glycosylation of proteins in the endoplasmic reticulum. 28860277 1 29 theme protein 201:207 arg1 channel 223:229 the protein translocation channel 197:229 the protein translocation channel 197:229 In metazoan organisms, the STT3A isoform of the oligosaccharyltransferase is localized adjacent to the protein translocation channel to catalyze co-translational N-linked glycosylation of proteins in the endoplasmic reticulum. 28860277 1 30 from glycosylation 269:281 arg1 reticulum 314:322 the endoplasmic reticulum 298:322 the endoplasmic reticulum 298:322 In metazoan organisms, the STT3A isoform of the oligosaccharyltransferase is localized adjacent to the protein translocation channel to catalyze co-translational N-linked glycosylation of proteins in the endoplasmic reticulum. 28860277 6 31 theme N-terminal 1067:1076 arg1 necessary 1102:1110 necessary 1102:1110 necessary 1102:1110 Deletion mutagenesis revealed that a conserved motif in the C-terminal tail of DC2 is critical for assembly into the STT3A complex, whereas the lumenal loop and the N-terminal cytoplasmic segment are necessary for the functional interaction between the STT3A and Sec61 complexes. 28860277 6 31 theme N-terminal 1067:1076 arg1 segment 1090:1096 the N-terminal cytoplasmic segment 1063:1096 the N-terminal cytoplasmic segment 1063:1096 Deletion mutagenesis revealed that a conserved motif in the C-terminal tail of DC2 is critical for assembly into the STT3A complex, whereas the lumenal loop and the N-terminal cytoplasmic segment are necessary for the functional interaction between the STT3A and Sec61 complexes. 28860277 3 32 theme proteins 614:621 arg1 N-glycosylation 595:609 co-translational N-glycosylation 578:609 co-translational N-glycosylation of proteins that mimics an STT3A phenotype 578:652 Using genetically modified human cells that are deficient in DC2 or KCP2 proteins, we show that loss of DC2 causes a defect in co-translational N-glycosylation of proteins that mimics an STT3A phenotype. 28860277 3 33 theme modified 469:476 arg1 cells 484:488 genetically modified human cells 457:488 genetically modified human cells that are deficient in DC2 or KCP2 proteins 457:531 Using genetically modified human cells that are deficient in DC2 or KCP2 proteins, we show that loss of DC2 causes a defect in co-translational N-glycosylation of proteins that mimics an STT3A phenotype. 28860277 1 34 theme translocation 209:221 arg1 channel 223:229 the protein translocation channel 197:229 the protein translocation channel 197:229 In metazoan organisms, the STT3A isoform of the oligosaccharyltransferase is localized adjacent to the protein translocation channel to catalyze co-translational N-linked glycosylation of proteins in the endoplasmic reticulum. 28860277 6 35 theme Deletion 902:909 arg1 mutagenesis 911:921 Deletion mutagenesis 902:921 Deletion mutagenesis 902:921 Deletion mutagenesis revealed that a conserved motif in the C-terminal tail of DC2 is critical for assembly into the STT3A complex, whereas the lumenal loop and the N-terminal cytoplasmic segment are necessary for the functional interaction between the STT3A and Sec61 complexes. 28860277 6 36 theme lumenal 1046:1052 arg1 necessary 1102:1110 necessary 1102:1110 necessary 1102:1110 Deletion mutagenesis revealed that a conserved motif in the C-terminal tail of DC2 is critical for assembly into the STT3A complex, whereas the lumenal loop and the N-terminal cytoplasmic segment are necessary for the functional interaction between the STT3A and Sec61 complexes. 28860277 6 36 theme lumenal 1046:1052 arg1 loop 1054:1057 the lumenal loop 1042:1057 the lumenal loop 1042:1057 Deletion mutagenesis revealed that a conserved motif in the C-terminal tail of DC2 is critical for assembly into the STT3A complex, whereas the lumenal loop and the N-terminal cytoplasmic segment are necessary for the functional interaction between the STT3A and Sec61 complexes. 28860277 3 37 gly N-glycosylation 595:609 arg1 proteins 614:621 proteins 614:621 proteins that mimics an STT3A phenotype 614:652 Using genetically modified human cells that are deficient in DC2 or KCP2 proteins, we show that loss of DC2 causes a defect in co-translational N-glycosylation of proteins that mimics an STT3A phenotype. 28860277 5 38 theme DC2- 825:828 arg1 complexes 855:863 DC2- and KCP2-deficient STT3A complexes 825:863 DC2- and KCP2-deficient STT3A complexes 825:863 Importantly, DC2- and KCP2-deficient STT3A complexes are stable and enzymatically active. 28860277 3 39 theme KCP2 519:522 arg1 proteins 524:531 KCP2 proteins 519:531 KCP2 proteins 519:531 Using genetically modified human cells that are deficient in DC2 or KCP2 proteins, we show that loss of DC2 causes a defect in co-translational N-glycosylation of proteins that mimics an STT3A phenotype. 28860277 6 40 theme DC2 981:983 arg1 tail 973:976 the C-terminal tail 958:976 the C-terminal tail of DC2 958:983 Deletion mutagenesis revealed that a conserved motif in the C-terminal tail of DC2 is critical for assembly into the STT3A complex, whereas the lumenal loop and the N-terminal cytoplasmic segment are necessary for the functional interaction between the STT3A and Sec61 complexes. 28860277 3 41 from deficient 499:507 arg1 DC2 512:514 DC2 512:514 DC2 512:514 Using genetically modified human cells that are deficient in DC2 or KCP2 proteins, we show that loss of DC2 causes a defect in co-translational N-glycosylation of proteins that mimics an STT3A phenotype. 28860277 3 41 from deficient 499:507 arg1 proteins 524:531 KCP2 proteins 519:531 KCP2 proteins 519:531 Using genetically modified human cells that are deficient in DC2 or KCP2 proteins, we show that loss of DC2 causes a defect in co-translational N-glycosylation of proteins that mimics an STT3A phenotype. 28860277 6 42 theme Sec61 1165:1169 arg1 complexes 1171:1179 the STT3A and Sec61 complexes 1151:1179 complexes 1171:1179 Deletion mutagenesis revealed that a conserved motif in the C-terminal tail of DC2 is critical for assembly into the STT3A complex, whereas the lumenal loop and the N-terminal cytoplasmic segment are necessary for the functional interaction between the STT3A and Sec61 complexes. 28860277 3 43 theme STT3A 638:642 arg1 phenotype 644:652 an STT3A phenotype 635:652 an STT3A phenotype 635:652 Using genetically modified human cells that are deficient in DC2 or KCP2 proteins, we show that loss of DC2 causes a defect in co-translational N-glycosylation of proteins that mimics an STT3A phenotype. 28860277 3 44 from defect 568:573 arg1 N-glycosylation 595:609 co-translational N-glycosylation 578:609 co-translational N-glycosylation of proteins that mimics an STT3A phenotype 578:652 Using genetically modified human cells that are deficient in DC2 or KCP2 proteins, we show that loss of DC2 causes a defect in co-translational N-glycosylation of proteins that mimics an STT3A phenotype. 28860277 4 45 theme STT3A 797:801 arg1 complex 803:809 the STT3A complex 793:809 the STT3A complex 793:809 Biochemical analysis showed that DC2 and KCP2 are responsible for mediating the interaction between the protein translocation channel and the STT3A complex. 28860277 1 46 theme STT3A 125:129 arg1 isoform 131:137 the STT3A isoform 121:137 the STT3A isoform of the oligosaccharyltransferase 121:170 In metazoan organisms, the STT3A isoform of the oligosaccharyltransferase is localized adjacent to the protein translocation channel to catalyze co-translational N-linked glycosylation of proteins in the endoplasmic reticulum. 28860277 1 47 theme co-translational 243:258 arg1 glycosylation 269:281 co-translational N-linked glycosylation 243:281 co-translational N-linked glycosylation of proteins in the endoplasmic reticulum 243:322 In metazoan organisms, the STT3A isoform of the oligosaccharyltransferase is localized adjacent to the protein translocation channel to catalyze co-translational N-linked glycosylation of proteins in the endoplasmic reticulum. 28860277 1 48 theme N-linked 260:267 arg1 glycosylation 269:281 co-translational N-linked glycosylation 243:281 co-translational N-linked glycosylation of proteins in the endoplasmic reticulum 243:322 In metazoan organisms, the STT3A isoform of the oligosaccharyltransferase is localized adjacent to the protein translocation channel to catalyze co-translational N-linked glycosylation of proteins in the endoplasmic reticulum. 24671695 7 0 theme isotope-labeled 1276:1290 arg1 standards 1301:1309 heavy isotope-labeled internal standards 1270:1309 heavy isotope-labeled internal standards coupled with LC-MS analysis 1270:1337 Specifically, the overall protein concentration and the non-glycosylated portion of the protein are quantified simultaneously by using heavy isotope-labeled internal standards coupled with LC-MS analysis, and the extent of site occupancy is accurately determined. 24671695 1 1 link N-linked 102:109 arg1 glycans 111:117 N-linked glycans 102:117 N-linked glycans 102:117 N-linked glycans are required to maintain appropriate biological functions on proteins. 24671695 4 2 contain containing 686:695 arg2 acid 706:709 aspartic acid 697:709 aspartic acid 697:709 By comparing the abundance of the resulting peptide containing aspartic acid against the one containing non-glycosylated asparagine, the glycosylation site occupancy can be evaluated. 24671695 4 2 contain containing 686:695 arg1 peptide 678:684 the resulting peptide 664:684 the resulting peptide containing aspartic acid 664:709 By comparing the abundance of the resulting peptide containing aspartic acid against the one containing non-glycosylated asparagine, the glycosylation site occupancy can be evaluated. 24671695 7 3 theme LC-MS 1324:1328 arg1 analysis 1330:1337 LC-MS analysis 1324:1337 LC-MS analysis 1324:1337 Specifically, the overall protein concentration and the non-glycosylated portion of the protein are quantified simultaneously by using heavy isotope-labeled internal standards coupled with LC-MS analysis, and the extent of site occupancy is accurately determined. 24671695 2 4 from step 337:340 arg1 understanding 345:357 understanding 345:357 understanding 345:357 Underglycosylation leads to many diseases in plants and animals; therefore, characterizing the extent of glycosylation on proteins is an important step in understanding, diagnosing, and treating diseases. 24671695 6 5 theme site 1034:1037 arg1 occupancy 1039:1047 the glycosylation site occupancy 1016:1047 the glycosylation site occupancy that does not rely on converting glycosylated peptides to their deglycosylated forms 1016:1132 To overcome this limitation, we developed a new method to measure the glycosylation site occupancy that does not rely on converting glycosylated peptides to their deglycosylated forms. 24671695 2 6 from diseases 223:230 arg1 animals 246:252 animals 246:252 animals 246:252 Underglycosylation leads to many diseases in plants and animals; therefore, characterizing the extent of glycosylation on proteins is an important step in understanding, diagnosing, and treating diseases. 24671695 2 6 from diseases 223:230 arg1 plants 235:240 plants 235:240 plants 235:240 Underglycosylation leads to many diseases in plants and animals; therefore, characterizing the extent of glycosylation on proteins is an important step in understanding, diagnosing, and treating diseases. 24671695 7 7 theme overall 1153:1159 arg1 concentration 1169:1181 the overall protein concentration 1149:1181 the overall protein concentration 1149:1181 Specifically, the overall protein concentration and the non-glycosylated portion of the protein are quantified simultaneously by using heavy isotope-labeled internal standards coupled with LC-MS analysis, and the extent of site occupancy is accurately determined. 24671695 8 8 theme glycosylation 1477:1489 arg1 site 1491:1494 a glycosylation site 1475:1494 a glycosylation site 1475:1494 The efficacy of the method was demonstrated by quantifying the occupancy of a glycosylation site on bovine fetuin. 24671695 9 9 theme PNGase 1614:1619 arg1 F 1621:1621 PNGase F 1614:1621 PNGase F 1614:1621 The developed method is the first work that measures the glycosylation site occupancy without using PNGase F, and it can be done in parallel with glycopeptide analysis because the glycan remains intact throughout the workflow. 24671695 6 10 theme glycosylation 1020:1032 arg1 occupancy 1039:1047 the glycosylation site occupancy 1016:1047 the glycosylation site occupancy that does not rely on converting glycosylated peptides to their deglycosylated forms 1016:1132 To overcome this limitation, we developed a new method to measure the glycosylation site occupancy that does not rely on converting glycosylated peptides to their deglycosylated forms. 24671695 7 11 theme heavy 1270:1274 arg1 standards 1301:1309 heavy isotope-labeled internal standards 1270:1309 heavy isotope-labeled internal standards coupled with LC-MS analysis 1270:1337 Specifically, the overall protein concentration and the non-glycosylated portion of the protein are quantified simultaneously by using heavy isotope-labeled internal standards coupled with LC-MS analysis, and the extent of site occupancy is accurately determined. 24671695 4 12 contain containing 727:736 arg1 one 723:725 one 723:725 one 723:725 By comparing the abundance of the resulting peptide containing aspartic acid against the one containing non-glycosylated asparagine, the glycosylation site occupancy can be evaluated. 24671695 4 12 contain containing 727:736 arg2 asparagine 755:764 non-glycosylated asparagine 738:764 non-glycosylated asparagine 738:764 By comparing the abundance of the resulting peptide containing aspartic acid against the one containing non-glycosylated asparagine, the glycosylation site occupancy can be evaluated. 24671695 3 13 gly glycosylation 412:424 arg2 site 426:429 the glycosylation site occupancy 408:439 the glycosylation site occupancy 408:439 To determine the glycosylation site occupancy, protein N-glycosidase F (PNGase F) is typically used to detach the glycan from the protein, during which the formerly glycosylated asparagine undergoes deamidation to become an aspartic acid. 24671695 3 13 gly glycosylation 412:424 arg2 occupancy 431:439 the glycosylation site occupancy 408:439 the glycosylation site occupancy 408:439 To determine the glycosylation site occupancy, protein N-glycosidase F (PNGase F) is typically used to detach the glycan from the protein, during which the formerly glycosylated asparagine undergoes deamidation to become an aspartic acid. 24671695 3 13 gly glycosylation 412:424 arg2 F 464:464 protein N-glycosidase F 442:464 protein N-glycosidase F (PNGase F) 442:475 To determine the glycosylation site occupancy, protein N-glycosidase F (PNGase F) is typically used to detach the glycan from the protein, during which the formerly glycosylated asparagine undergoes deamidation to become an aspartic acid. 24671695 4 14 theme site 785:788 arg1 occupancy 790:798 the glycosylation site occupancy 767:798 the glycosylation site occupancy 767:798 By comparing the abundance of the resulting peptide containing aspartic acid against the one containing non-glycosylated asparagine, the glycosylation site occupancy can be evaluated. 24671695 9 15 theme glycosylation 1571:1583 arg1 occupancy 1590:1598 the glycosylation site occupancy 1567:1598 the glycosylation site occupancy 1567:1598 The developed method is the first work that measures the glycosylation site occupancy without using PNGase F, and it can be done in parallel with glycopeptide analysis because the glycan remains intact throughout the workflow. 24671695 8 16 gly glycosylation 1477:1489 arg2 site 1491:1494 a glycosylation site 1475:1494 a glycosylation site 1475:1494 The efficacy of the method was demonstrated by quantifying the occupancy of a glycosylation site on bovine fetuin. 24671695 7 17 theme protein 1223:1229 arg1 portion 1208:1214 the non-glycosylated portion 1187:1214 the non-glycosylated portion of the protein 1187:1229 Specifically, the overall protein concentration and the non-glycosylated portion of the protein are quantified simultaneously by using heavy isotope-labeled internal standards coupled with LC-MS analysis, and the extent of site occupancy is accurately determined. 24671695 7 17 theme protein 1223:1229 arg1 concentration 1169:1181 the overall protein concentration 1149:1181 the overall protein concentration 1149:1181 Specifically, the overall protein concentration and the non-glycosylated portion of the protein are quantified simultaneously by using heavy isotope-labeled internal standards coupled with LC-MS analysis, and the extent of site occupancy is accurately determined. 24671695 6 18 theme glycosylated 1082:1093 arg1 peptides 1095:1102 glycosylated peptides 1082:1102 glycosylated peptides 1082:1102 To overcome this limitation, we developed a new method to measure the glycosylation site occupancy that does not rely on converting glycosylated peptides to their deglycosylated forms. 24671695 2 19 theme glycosylation 295:307 arg1 extent 285:290 the extent 281:290 the extent of glycosylation on proteins 281:319 Underglycosylation leads to many diseases in plants and animals; therefore, characterizing the extent of glycosylation on proteins is an important step in understanding, diagnosing, and treating diseases. 24671695 4 20 theme peptide 678:684 arg1 abundance 651:659 the abundance 647:659 the abundance of the resulting peptide containing aspartic acid 647:709 By comparing the abundance of the resulting peptide containing aspartic acid against the one containing non-glycosylated asparagine, the glycosylation site occupancy can be evaluated. 24671695 5 21 theme chemical 886:893 arg1 deamidation 895:905 spontaneous chemical deamidation 874:905 spontaneous chemical deamidation of the non-glycosylated asparagine 874:940 However, this approach can give inaccurate results when spontaneous chemical deamidation of the non-glycosylated asparagine occurs. 24671695 4 22 gly glycosylation 771:783 arg2 occupancy 790:798 the glycosylation site occupancy 767:798 the glycosylation site occupancy 767:798 By comparing the abundance of the resulting peptide containing aspartic acid against the one containing non-glycosylated asparagine, the glycosylation site occupancy can be evaluated. 24671695 4 22 gly glycosylation 771:783 arg2 site 785:788 the glycosylation site occupancy 767:798 the glycosylation site occupancy 767:798 By comparing the abundance of the resulting peptide containing aspartic acid against the one containing non-glycosylated asparagine, the glycosylation site occupancy can be evaluated. 24671695 8 23 theme method 1419:1424 arg1 efficacy 1403:1410 The efficacy 1399:1410 The efficacy of the method 1399:1424 The efficacy of the method was demonstrated by quantifying the occupancy of a glycosylation site on bovine fetuin. 24671695 6 24 theme deglycosylated 1113:1126 arg1 forms 1128:1132 their deglycosylated forms 1107:1132 their deglycosylated forms 1107:1132 To overcome this limitation, we developed a new method to measure the glycosylation site occupancy that does not rely on converting glycosylated peptides to their deglycosylated forms. 24671695 9 25 with parallel 1646:1653 arg1 analysis 1673:1680 glycopeptide analysis 1660:1680 glycopeptide analysis 1660:1680 The developed method is the first work that measures the glycosylation site occupancy without using PNGase F, and it can be done in parallel with glycopeptide analysis because the glycan remains intact throughout the workflow. 24671695 7 26 theme internal 1292:1299 arg1 standards 1301:1309 heavy isotope-labeled internal standards 1270:1309 heavy isotope-labeled internal standards coupled with LC-MS analysis 1270:1337 Specifically, the overall protein concentration and the non-glycosylated portion of the protein are quantified simultaneously by using heavy isotope-labeled internal standards coupled with LC-MS analysis, and the extent of site occupancy is accurately determined. 24671695 3 27 theme glycosylated 560:571 arg1 asparagine 573:582 the formerly glycosylated asparagine 547:582 the formerly glycosylated asparagine 547:582 To determine the glycosylation site occupancy, protein N-glycosidase F (PNGase F) is typically used to detach the glycan from the protein, during which the formerly glycosylated asparagine undergoes deamidation to become an aspartic acid. 24671695 8 28 from occupancy 1462:1470 arg1 fetuin 1506:1511 bovine fetuin 1499:1511 bovine fetuin 1499:1511 The efficacy of the method was demonstrated by quantifying the occupancy of a glycosylation site on bovine fetuin. 24671695 3 29 theme protein 442:448 arg1 F 464:464 protein N-glycosidase F 442:464 protein N-glycosidase F (PNGase F) 442:475 To determine the glycosylation site occupancy, protein N-glycosidase F (PNGase F) is typically used to detach the glycan from the protein, during which the formerly glycosylated asparagine undergoes deamidation to become an aspartic acid. 24671695 3 29 theme protein 442:448 arg1 F 474:474 PNGase F 467:474 PNGase F 467:474 To determine the glycosylation site occupancy, protein N-glycosidase F (PNGase F) is typically used to detach the glycan from the protein, during which the formerly glycosylated asparagine undergoes deamidation to become an aspartic acid. 24671695 3 29 theme protein 442:448 arg1 occupancy 431:439 the glycosylation site occupancy 408:439 the glycosylation site occupancy 408:439 To determine the glycosylation site occupancy, protein N-glycosidase F (PNGase F) is typically used to detach the glycan from the protein, during which the formerly glycosylated asparagine undergoes deamidation to become an aspartic acid. 24671695 0 30 theme Absolute 0:7 arg1 quantitation 9:20 Absolute quantitation 0:20 Absolute quantitation of glycosylation site occupancy 0:52 Absolute quantitation of glycosylation site occupancy using isotopically labeled standards and LC-MS. 24671695 2 31 theme important 327:335 arg1 step 337:340 an important step 324:340 an important step in understanding 324:357 Underglycosylation leads to many diseases in plants and animals; therefore, characterizing the extent of glycosylation on proteins is an important step in understanding, diagnosing, and treating diseases. 24671695 7 32 theme occupancy 1363:1371 arg1 extent 1348:1353 the extent 1344:1353 the extent of site occupancy 1344:1371 Specifically, the overall protein concentration and the non-glycosylated portion of the protein are quantified simultaneously by using heavy isotope-labeled internal standards coupled with LC-MS analysis, and the extent of site occupancy is accurately determined. 24671695 3 33 theme N-glycosidase 450:462 arg1 F 464:464 protein N-glycosidase F 442:464 protein N-glycosidase F (PNGase F) 442:475 To determine the glycosylation site occupancy, protein N-glycosidase F (PNGase F) is typically used to detach the glycan from the protein, during which the formerly glycosylated asparagine undergoes deamidation to become an aspartic acid. 24671695 3 33 theme N-glycosidase 450:462 arg1 F 474:474 PNGase F 467:474 PNGase F 467:474 To determine the glycosylation site occupancy, protein N-glycosidase F (PNGase F) is typically used to detach the glycan from the protein, during which the formerly glycosylated asparagine undergoes deamidation to become an aspartic acid. 24671695 3 33 theme N-glycosidase 450:462 arg1 occupancy 431:439 the glycosylation site occupancy 408:439 the glycosylation site occupancy 408:439 To determine the glycosylation site occupancy, protein N-glycosidase F (PNGase F) is typically used to detach the glycan from the protein, during which the formerly glycosylated asparagine undergoes deamidation to become an aspartic acid. 24671695 0 34 theme glycosylation 25:37 arg1 occupancy 44:52 glycosylation site occupancy 25:52 glycosylation site occupancy 25:52 Absolute quantitation of glycosylation site occupancy using isotopically labeled standards and LC-MS. 24671695 6 35 gly glycosylated 1082:1093 arg1 peptides 1095:1102 glycosylated peptides 1082:1102 glycosylated peptides 1082:1102 To overcome this limitation, we developed a new method to measure the glycosylation site occupancy that does not rely on converting glycosylated peptides to their deglycosylated forms. 24671695 9 36 theme glycopeptide 1660:1671 arg1 analysis 1673:1680 glycopeptide analysis 1660:1680 glycopeptide analysis 1660:1680 The developed method is the first work that measures the glycosylation site occupancy without using PNGase F, and it can be done in parallel with glycopeptide analysis because the glycan remains intact throughout the workflow. 24671695 4 37 theme glycosylation 771:783 arg1 occupancy 790:798 the glycosylation site occupancy 767:798 the glycosylation site occupancy 767:798 By comparing the abundance of the resulting peptide containing aspartic acid against the one containing non-glycosylated asparagine, the glycosylation site occupancy can be evaluated. 24671695 5 38 theme inaccurate 850:859 arg1 results 861:867 inaccurate results 850:867 inaccurate results 850:867 However, this approach can give inaccurate results when spontaneous chemical deamidation of the non-glycosylated asparagine occurs. 24671695 1 39 theme N-linked 102:109 arg1 glycans 111:117 N-linked glycans 102:117 N-linked glycans 102:117 N-linked glycans are required to maintain appropriate biological functions on proteins. 24671695 9 40 theme first 1542:1546 arg1 method 1528:1533 The developed method 1514:1533 The developed method 1514:1533 The developed method is the first work that measures the glycosylation site occupancy without using PNGase F, and it can be done in parallel with glycopeptide analysis because the glycan remains intact throughout the workflow. 24671695 9 40 theme first 1542:1546 arg1 work 1548:1551 the first work 1538:1551 the first work that measures the glycosylation site occupancy without using PNGase F 1538:1621 The developed method is the first work that measures the glycosylation site occupancy without using PNGase F, and it can be done in parallel with glycopeptide analysis because the glycan remains intact throughout the workflow. 24671695 9 41 gly glycosylation 1571:1583 arg2 occupancy 1590:1598 the glycosylation site occupancy 1567:1598 the glycosylation site occupancy 1567:1598 The developed method is the first work that measures the glycosylation site occupancy without using PNGase F, and it can be done in parallel with glycopeptide analysis because the glycan remains intact throughout the workflow. 24671695 9 41 gly glycosylation 1571:1583 arg2 site 1585:1588 the glycosylation site occupancy 1567:1598 the glycosylation site occupancy 1567:1598 The developed method is the first work that measures the glycosylation site occupancy without using PNGase F, and it can be done in parallel with glycopeptide analysis because the glycan remains intact throughout the workflow. 24671695 2 42 from extent 285:290 arg1 proteins 312:319 proteins 312:319 proteins 312:319 Underglycosylation leads to many diseases in plants and animals; therefore, characterizing the extent of glycosylation on proteins is an important step in understanding, diagnosing, and treating diseases. 24671695 4 43 theme aspartic 697:704 arg1 acid 706:709 aspartic acid 697:709 aspartic acid 697:709 By comparing the abundance of the resulting peptide containing aspartic acid against the one containing non-glycosylated asparagine, the glycosylation site occupancy can be evaluated. 24671695 0 44 theme occupancy 44:52 arg1 quantitation 9:20 Absolute quantitation 0:20 Absolute quantitation of glycosylation site occupancy 0:52 Absolute quantitation of glycosylation site occupancy using isotopically labeled standards and LC-MS. 24671695 6 45 theme new 994:996 arg1 method 998:1003 a new method 992:1003 a new method to measure the glycosylation site occupancy that does not rely on converting glycosylated peptides to their deglycosylated forms 992:1132 To overcome this limitation, we developed a new method to measure the glycosylation site occupancy that does not rely on converting glycosylated peptides to their deglycosylated forms. 24671695 7 46 theme site 1358:1361 arg1 occupancy 1363:1371 site occupancy 1358:1371 site occupancy 1358:1371 Specifically, the overall protein concentration and the non-glycosylated portion of the protein are quantified simultaneously by using heavy isotope-labeled internal standards coupled with LC-MS analysis, and the extent of site occupancy is accurately determined. 24671695 4 47 theme resulting 668:676 arg1 peptide 678:684 the resulting peptide 664:684 the resulting peptide containing aspartic acid 664:709 By comparing the abundance of the resulting peptide containing aspartic acid against the one containing non-glycosylated asparagine, the glycosylation site occupancy can be evaluated. 24671695 3 48 theme PNGase 467:472 arg1 F 464:464 protein N-glycosidase F 442:464 protein N-glycosidase F (PNGase F) 442:475 To determine the glycosylation site occupancy, protein N-glycosidase F (PNGase F) is typically used to detach the glycan from the protein, during which the formerly glycosylated asparagine undergoes deamidation to become an aspartic acid. 24671695 3 48 theme PNGase 467:472 arg1 F 474:474 PNGase F 467:474 PNGase F 467:474 To determine the glycosylation site occupancy, protein N-glycosidase F (PNGase F) is typically used to detach the glycan from the protein, during which the formerly glycosylated asparagine undergoes deamidation to become an aspartic acid. 24671695 0 49 theme site 39:42 arg1 occupancy 44:52 glycosylation site occupancy 25:52 glycosylation site occupancy 25:52 Absolute quantitation of glycosylation site occupancy using isotopically labeled standards and LC-MS. 24671695 4 50 gly non-glycosylated 738:753 arg1 asparagine 755:764 non-glycosylated asparagine 738:764 non-glycosylated asparagine 738:764 By comparing the abundance of the resulting peptide containing aspartic acid against the one containing non-glycosylated asparagine, the glycosylation site occupancy can be evaluated. 24671695 5 51 theme spontaneous 874:884 arg1 deamidation 895:905 spontaneous chemical deamidation 874:905 spontaneous chemical deamidation of the non-glycosylated asparagine 874:940 However, this approach can give inaccurate results when spontaneous chemical deamidation of the non-glycosylated asparagine occurs. 24671695 3 52 theme glycosylation 412:424 arg1 F 464:464 protein N-glycosidase F 442:464 protein N-glycosidase F (PNGase F) 442:475 To determine the glycosylation site occupancy, protein N-glycosidase F (PNGase F) is typically used to detach the glycan from the protein, during which the formerly glycosylated asparagine undergoes deamidation to become an aspartic acid. 24671695 3 52 theme glycosylation 412:424 arg1 occupancy 431:439 the glycosylation site occupancy 408:439 the glycosylation site occupancy 408:439 To determine the glycosylation site occupancy, protein N-glycosidase F (PNGase F) is typically used to detach the glycan from the protein, during which the formerly glycosylated asparagine undergoes deamidation to become an aspartic acid. 24671695 5 53 theme non-glycosylated 914:929 arg1 asparagine 931:940 the non-glycosylated asparagine 910:940 the non-glycosylated asparagine 910:940 However, this approach can give inaccurate results when spontaneous chemical deamidation of the non-glycosylated asparagine occurs. 24671695 6 54 gly deglycosylated 1113:1126 arg1 forms 1128:1132 their deglycosylated forms 1107:1132 their deglycosylated forms 1107:1132 To overcome this limitation, we developed a new method to measure the glycosylation site occupancy that does not rely on converting glycosylated peptides to their deglycosylated forms. 24671695 7 55 gly non-glycosylated 1191:1206 arg1 portion 1208:1214 the non-glycosylated portion 1187:1214 the non-glycosylated portion of the protein 1187:1229 Specifically, the overall protein concentration and the non-glycosylated portion of the protein are quantified simultaneously by using heavy isotope-labeled internal standards coupled with LC-MS analysis, and the extent of site occupancy is accurately determined. 24671695 3 56 theme site 426:429 arg1 F 464:464 protein N-glycosidase F 442:464 protein N-glycosidase F (PNGase F) 442:475 To determine the glycosylation site occupancy, protein N-glycosidase F (PNGase F) is typically used to detach the glycan from the protein, during which the formerly glycosylated asparagine undergoes deamidation to become an aspartic acid. 24671695 3 56 theme site 426:429 arg1 occupancy 431:439 the glycosylation site occupancy 408:439 the glycosylation site occupancy 408:439 To determine the glycosylation site occupancy, protein N-glycosidase F (PNGase F) is typically used to detach the glycan from the protein, during which the formerly glycosylated asparagine undergoes deamidation to become an aspartic acid. 24671695 5 57 gly non-glycosylated 914:929 arg1 asparagine 931:940 the non-glycosylated asparagine 910:940 the non-glycosylated asparagine 910:940 However, this approach can give inaccurate results when spontaneous chemical deamidation of the non-glycosylated asparagine occurs. 24671695 0 58 gly glycosylation 25:37 arg2 occupancy 44:52 glycosylation site occupancy 25:52 glycosylation site occupancy 25:52 Absolute quantitation of glycosylation site occupancy using isotopically labeled standards and LC-MS. 24671695 0 58 gly glycosylation 25:37 arg2 site 39:42 glycosylation site occupancy 25:52 glycosylation site occupancy 25:52 Absolute quantitation of glycosylation site occupancy using isotopically labeled standards and LC-MS. 24671695 3 59 gly glycosylated 560:571 arg1 asparagine 573:582 the formerly glycosylated asparagine 547:582 the formerly glycosylated asparagine 547:582 To determine the glycosylation site occupancy, protein N-glycosidase F (PNGase F) is typically used to detach the glycan from the protein, during which the formerly glycosylated asparagine undergoes deamidation to become an aspartic acid. 24671695 8 60 theme bovine 1499:1504 arg1 fetuin 1506:1511 bovine fetuin 1499:1511 bovine fetuin 1499:1511 The efficacy of the method was demonstrated by quantifying the occupancy of a glycosylation site on bovine fetuin. 24671695 7 61 theme non-glycosylated 1191:1206 arg1 portion 1208:1214 the non-glycosylated portion 1187:1214 the non-glycosylated portion of the protein 1187:1229 Specifically, the overall protein concentration and the non-glycosylated portion of the protein are quantified simultaneously by using heavy isotope-labeled internal standards coupled with LC-MS analysis, and the extent of site occupancy is accurately determined. 24671695 6 62 gly glycosylation 1020:1032 arg2 occupancy 1039:1047 the glycosylation site occupancy 1016:1047 the glycosylation site occupancy that does not rely on converting glycosylated peptides to their deglycosylated forms 1016:1132 To overcome this limitation, we developed a new method to measure the glycosylation site occupancy that does not rely on converting glycosylated peptides to their deglycosylated forms. 24671695 6 62 gly glycosylation 1020:1032 arg2 site 1034:1037 the glycosylation site occupancy 1016:1047 the glycosylation site occupancy that does not rely on converting glycosylated peptides to their deglycosylated forms 1016:1132 To overcome this limitation, we developed a new method to measure the glycosylation site occupancy that does not rely on converting glycosylated peptides to their deglycosylated forms. 24671695 2 63 dep step 337:340 arg1 diagnosing 360:369 diagnosing 360:369 diagnosing 360:369 Underglycosylation leads to many diseases in plants and animals; therefore, characterizing the extent of glycosylation on proteins is an important step in understanding, diagnosing, and treating diseases. 24671695 2 63 dep step 337:340 arg1 treating 376:383 treating 376:383 treating diseases 376:392 Underglycosylation leads to many diseases in plants and animals; therefore, characterizing the extent of glycosylation on proteins is an important step in understanding, diagnosing, and treating diseases. 24671695 8 64 gly occupancy 1462:1470 arg2 site 1491:1494 a glycosylation site 1475:1494 a glycosylation site 1475:1494 The efficacy of the method was demonstrated by quantifying the occupancy of a glycosylation site on bovine fetuin. 24671695 8 65 theme site 1491:1494 arg1 occupancy 1462:1470 the occupancy 1458:1470 the occupancy of a glycosylation site on bovine fetuin 1458:1511 The efficacy of the method was demonstrated by quantifying the occupancy of a glycosylation site on bovine fetuin. 24671695 1 66 theme appropriate 144:154 arg1 functions 167:175 appropriate biological functions 144:175 appropriate biological functions 144:175 N-linked glycans are required to maintain appropriate biological functions on proteins. 24671695 4 67 theme non-glycosylated 738:753 arg1 asparagine 755:764 non-glycosylated asparagine 738:764 non-glycosylated asparagine 738:764 By comparing the abundance of the resulting peptide containing aspartic acid against the one containing non-glycosylated asparagine, the glycosylation site occupancy can be evaluated. 24671695 2 68 theme many 218:221 arg1 diseases 223:230 many diseases 218:230 many diseases in plants and animals 218:252 Underglycosylation leads to many diseases in plants and animals; therefore, characterizing the extent of glycosylation on proteins is an important step in understanding, diagnosing, and treating diseases. 24671695 9 69 theme site 1585:1588 arg1 occupancy 1590:1598 the glycosylation site occupancy 1567:1598 the glycosylation site occupancy 1567:1598 The developed method is the first work that measures the glycosylation site occupancy without using PNGase F, and it can be done in parallel with glycopeptide analysis because the glycan remains intact throughout the workflow. 24671695 1 70 theme biological 156:165 arg1 functions 167:175 appropriate biological functions 144:175 appropriate biological functions 144:175 N-linked glycans are required to maintain appropriate biological functions on proteins. 24671695 9 71 gly glycopeptide 1660:1671 arg2 glycopeptide 1660:1671 glycopeptide analysis 1660:1680 glycopeptide analysis 1660:1680 The developed method is the first work that measures the glycosylation site occupancy without using PNGase F, and it can be done in parallel with glycopeptide analysis because the glycan remains intact throughout the workflow. 24671695 0 72 theme labeled 73:79 arg1 standards 81:89 isotopically labeled standards 60:89 isotopically labeled standards 60:89 Absolute quantitation of glycosylation site occupancy using isotopically labeled standards and LC-MS. 24671695 9 73 theme developed 1518:1526 arg1 method 1528:1533 The developed method 1514:1533 The developed method 1514:1533 The developed method is the first work that measures the glycosylation site occupancy without using PNGase F, and it can be done in parallel with glycopeptide analysis because the glycan remains intact throughout the workflow. 24671695 9 73 theme developed 1518:1526 arg1 work 1548:1551 the first work 1538:1551 the first work that measures the glycosylation site occupancy without using PNGase F 1538:1621 The developed method is the first work that measures the glycosylation site occupancy without using PNGase F, and it can be done in parallel with glycopeptide analysis because the glycan remains intact throughout the workflow. 24671695 3 74 theme aspartic 619:626 arg1 acid 628:631 an aspartic acid 616:631 an aspartic acid 616:631 To determine the glycosylation site occupancy, protein N-glycosidase F (PNGase F) is typically used to detach the glycan from the protein, during which the formerly glycosylated asparagine undergoes deamidation to become an aspartic acid. 24671695 5 75 theme asparagine 931:940 arg1 deamidation 895:905 spontaneous chemical deamidation 874:905 spontaneous chemical deamidation of the non-glycosylated asparagine 874:940 However, this approach can give inaccurate results when spontaneous chemical deamidation of the non-glycosylated asparagine occurs. 24671695 3 76 from protein 525:531 arg1 glycan 509:514 the glycan 505:514 the glycan 505:514 To determine the glycosylation site occupancy, protein N-glycosidase F (PNGase F) is typically used to detach the glycan from the protein, during which the formerly glycosylated asparagine undergoes deamidation to become an aspartic acid. 24671695 7 77 theme protein 1161:1167 arg1 concentration 1169:1181 the overall protein concentration 1149:1181 the overall protein concentration 1149:1181 Specifically, the overall protein concentration and the non-glycosylated portion of the protein are quantified simultaneously by using heavy isotope-labeled internal standards coupled with LC-MS analysis, and the extent of site occupancy is accurately determined. 24105912 6 0 theme DEP 1110:1112 arg1 isolation 1114:1122 DEP isolation 1110:1122 DEP isolation 1110:1122 A single round of DEP isolation provided greater NP enrichment than sorting with PSA-NCAM, which is considered an NP marker. 24105912 7 1 theme cell 1231:1234 arg1 glycosylation 1253:1265 cell surface N-linked glycosylation 1231:1265 cell surface N-linked glycosylation 1231:1265 Additionally, cell surface N-linked glycosylation was found to significantly affect cell fate-specific electrophysiological properties, providing a molecular basis for the cell membrane characteristics. 24105912 8 2 theme neural 1550:1555 arg1 lineage 1557:1563 the neural lineage 1546:1563 the neural lineage 1546:1563 Inherent plasma membrane biophysical properties are thus sufficient to define progenitor cells of differing fate potential in the neural lineage, can be used to specifically isolate these cells, and are linked to patterns of glycosylation on the cell surface. 24105912 6 3 theme isolation 1114:1122 arg1 round 1101:1105 A single round 1092:1105 A single round of DEP isolation 1092:1122 A single round of DEP isolation provided greater NP enrichment than sorting with PSA-NCAM, which is considered an NP marker. 24105912 8 4 theme cell 1666:1669 arg1 surface 1671:1677 the cell surface 1662:1677 the cell surface 1662:1677 Inherent plasma membrane biophysical properties are thus sufficient to define progenitor cells of differing fate potential in the neural lineage, can be used to specifically isolate these cells, and are linked to patterns of glycosylation on the cell surface. 24105912 8 5 theme plasma 1429:1434 arg1 properties 1457:1466 Inherent plasma membrane biophysical properties 1420:1466 Inherent plasma membrane biophysical properties 1420:1466 Inherent plasma membrane biophysical properties are thus sufficient to define progenitor cells of differing fate potential in the neural lineage, can be used to specifically isolate these cells, and are linked to patterns of glycosylation on the cell surface. 24105912 7 6 link N-linked 1244:1251 arg1 glycosylation 1253:1265 cell surface N-linked glycosylation 1231:1265 cell surface N-linked glycosylation 1231:1265 Additionally, cell surface N-linked glycosylation was found to significantly affect cell fate-specific electrophysiological properties, providing a molecular basis for the cell membrane characteristics. 24105912 8 7 used used 1573:1576 arg2 properties 1457:1466 Inherent plasma membrane biophysical properties 1420:1466 Inherent plasma membrane biophysical properties 1420:1466 Inherent plasma membrane biophysical properties are thus sufficient to define progenitor cells of differing fate potential in the neural lineage, can be used to specifically isolate these cells, and are linked to patterns of glycosylation on the cell surface. 24105912 2 8 theme progenitor 336:345 arg1 cells 347:351 the different progenitor cells 322:351 the different progenitor cells 322:351 Accurately identifying and characterizing the different progenitor cells in this lineage has continued to be a challenge for the field. 24105912 3 9 theme astrogenic 543:552 arg1 APs 567:569 APs 567:569 APs 567:569 We found previously that populations of NSPCs with more neurogenic progenitors (NPs) can be distinguished from those with more astrogenic progenitors (APs) by their inherent biophysical properties, specifically the electrophysiological property of whole cell membrane capacitance, which we characterized with dielectrophoresis (DEP). 24105912 3 9 theme astrogenic 543:552 arg1 progenitors 554:564 more astrogenic progenitors 538:564 more astrogenic progenitors (APs) 538:570 We found previously that populations of NSPCs with more neurogenic progenitors (NPs) can be distinguished from those with more astrogenic progenitors (APs) by their inherent biophysical properties, specifically the electrophysiological property of whole cell membrane capacitance, which we characterized with dielectrophoresis (DEP). 24105912 0 10 from progenitors 48:58 arg1 lineage 74:80 the neural lineage 63:80 the neural lineage 63:80 Membrane biophysics define neuron and astrocyte progenitors in the neural lineage. 24105912 8 11 from patterns 1633:1640 arg1 surface 1671:1677 the cell surface 1662:1677 the cell surface 1662:1677 Inherent plasma membrane biophysical properties are thus sufficient to define progenitor cells of differing fate potential in the neural lineage, can be used to specifically isolate these cells, and are linked to patterns of glycosylation on the cell surface. 24105912 3 12 theme neurogenic 472:481 arg1 NPs 496:498 NPs 496:498 NPs 496:498 We found previously that populations of NSPCs with more neurogenic progenitors (NPs) can be distinguished from those with more astrogenic progenitors (APs) by their inherent biophysical properties, specifically the electrophysiological property of whole cell membrane capacitance, which we characterized with dielectrophoresis (DEP). 24105912 3 12 theme neurogenic 472:481 arg1 progenitors 483:493 more neurogenic progenitors 467:493 more neurogenic progenitors (NPs) 467:499 We found previously that populations of NSPCs with more neurogenic progenitors (NPs) can be distinguished from those with more astrogenic progenitors (APs) by their inherent biophysical properties, specifically the electrophysiological property of whole cell membrane capacitance, which we characterized with dielectrophoresis (DEP). 24105912 4 13 theme electrophysiological 785:804 arg1 properties 806:815 inherent electrophysiological properties 776:815 inherent electrophysiological properties 776:815 Here, we hypothesize that inherent electrophysiological properties are sufficient to define NPs and APs and test this by determining whether isolation of cells solely by these properties specifically separates NPs and APs. 24105912 1 14 theme self-renewing 157:169 arg1 cells 176:180 self-renewing stem cells 157:180 self-renewing stem cells 157:180 Neural stem and progenitor cells (NSPCs) are heterogeneous populations of self-renewing stem cells and more committed progenitors that differentiate into neurons, astrocytes, and oligodendrocytes. 24105912 4 15 theme inherent 776:783 arg1 properties 806:815 inherent electrophysiological properties 776:815 inherent electrophysiological properties 776:815 Here, we hypothesize that inherent electrophysiological properties are sufficient to define NPs and APs and test this by determining whether isolation of cells solely by these properties specifically separates NPs and APs. 24105912 1 16 theme stem 171:174 arg1 cells 176:180 self-renewing stem cells 157:180 self-renewing stem cells 157:180 Neural stem and progenitor cells (NSPCs) are heterogeneous populations of self-renewing stem cells and more committed progenitors that differentiate into neurons, astrocytes, and oligodendrocytes. 24105912 8 17 from cells 1509:1513 arg1 lineage 1557:1563 the neural lineage 1546:1563 the neural lineage 1546:1563 Inherent plasma membrane biophysical properties are thus sufficient to define progenitor cells of differing fate potential in the neural lineage, can be used to specifically isolate these cells, and are linked to patterns of glycosylation on the cell surface. 24105912 7 18 theme electrophysiological 1320:1339 arg1 properties 1341:1350 cell fate-specific electrophysiological properties 1301:1350 cell fate-specific electrophysiological properties 1301:1350 Additionally, cell surface N-linked glycosylation was found to significantly affect cell fate-specific electrophysiological properties, providing a molecular basis for the cell membrane characteristics. 24105912 7 19 theme surface 1236:1242 arg1 glycosylation 1253:1265 cell surface N-linked glycosylation 1231:1265 cell surface N-linked glycosylation 1231:1265 Additionally, cell surface N-linked glycosylation was found to significantly affect cell fate-specific electrophysiological properties, providing a molecular basis for the cell membrane characteristics. 24105912 1 20 theme Neural 83:88 arg1 NSPCs 117:121 NSPCs 117:121 NSPCs 117:121 Neural stem and progenitor cells (NSPCs) are heterogeneous populations of self-renewing stem cells and more committed progenitors that differentiate into neurons, astrocytes, and oligodendrocytes. 24105912 1 20 theme Neural 83:88 arg1 stem 90:93 Neural stem and progenitor cells 83:114 stem 90:93 Neural stem and progenitor cells (NSPCs) are heterogeneous populations of self-renewing stem cells and more committed progenitors that differentiate into neurons, astrocytes, and oligodendrocytes. 24105912 1 20 theme Neural 83:88 arg1 cells 110:114 Neural stem and progenitor cells 83:114 cells 110:114 Neural stem and progenitor cells (NSPCs) are heterogeneous populations of self-renewing stem cells and more committed progenitors that differentiate into neurons, astrocytes, and oligodendrocytes. 24105912 1 20 theme Neural 83:88 arg1 populations 142:152 heterogeneous populations 128:152 heterogeneous populations of self-renewing stem cells and more committed progenitors that differentiate into neurons, astrocytes, and oligodendrocytes 128:277 Neural stem and progenitor cells (NSPCs) are heterogeneous populations of self-renewing stem cells and more committed progenitors that differentiate into neurons, astrocytes, and oligodendrocytes. 24105912 5 21 from enriched 998:1005 arg1 fractions 1019:1027 distinct fractions 1010:1027 distinct fractions after separation by electrophysiological properties using DEP 1010:1089 We found NPs and APs are enriched in distinct fractions after separation by electrophysiological properties using DEP. 24105912 1 22 theme cells 176:180 arg1 stem 90:93 Neural stem and progenitor cells 83:114 stem 90:93 Neural stem and progenitor cells (NSPCs) are heterogeneous populations of self-renewing stem cells and more committed progenitors that differentiate into neurons, astrocytes, and oligodendrocytes. 24105912 1 22 theme cells 176:180 arg1 cells 110:114 Neural stem and progenitor cells 83:114 cells 110:114 Neural stem and progenitor cells (NSPCs) are heterogeneous populations of self-renewing stem cells and more committed progenitors that differentiate into neurons, astrocytes, and oligodendrocytes. 24105912 1 22 theme cells 176:180 arg1 populations 142:152 heterogeneous populations 128:152 heterogeneous populations of self-renewing stem cells and more committed progenitors that differentiate into neurons, astrocytes, and oligodendrocytes 128:277 Neural stem and progenitor cells (NSPCs) are heterogeneous populations of self-renewing stem cells and more committed progenitors that differentiate into neurons, astrocytes, and oligodendrocytes. 24105912 0 23 theme Membrane 0:7 arg1 biophysics 9:18 Membrane biophysics 0:18 Membrane biophysics 0:18 Membrane biophysics define neuron and astrocyte progenitors in the neural lineage. 24105912 2 24 theme different 326:334 arg1 cells 347:351 the different progenitor cells 322:351 the different progenitor cells 322:351 Accurately identifying and characterizing the different progenitor cells in this lineage has continued to be a challenge for the field. 24105912 3 25 theme whole 664:668 arg1 capacitance 684:694 whole cell membrane capacitance 664:694 whole cell membrane capacitance 664:694 We found previously that populations of NSPCs with more neurogenic progenitors (NPs) can be distinguished from those with more astrogenic progenitors (APs) by their inherent biophysical properties, specifically the electrophysiological property of whole cell membrane capacitance, which we characterized with dielectrophoresis (DEP). 24105912 3 26 with NSPCs 456:460 arg1 NPs 496:498 NPs 496:498 NPs 496:498 We found previously that populations of NSPCs with more neurogenic progenitors (NPs) can be distinguished from those with more astrogenic progenitors (APs) by their inherent biophysical properties, specifically the electrophysiological property of whole cell membrane capacitance, which we characterized with dielectrophoresis (DEP). 24105912 3 26 with NSPCs 456:460 arg1 progenitors 483:493 more neurogenic progenitors 467:493 more neurogenic progenitors (NPs) 467:499 We found previously that populations of NSPCs with more neurogenic progenitors (NPs) can be distinguished from those with more astrogenic progenitors (APs) by their inherent biophysical properties, specifically the electrophysiological property of whole cell membrane capacitance, which we characterized with dielectrophoresis (DEP). 24105912 7 27 theme cell 1389:1392 arg1 characteristics 1403:1417 the cell membrane characteristics 1385:1417 the cell membrane characteristics 1385:1417 Additionally, cell surface N-linked glycosylation was found to significantly affect cell fate-specific electrophysiological properties, providing a molecular basis for the cell membrane characteristics. 24105912 5 28 theme electrophysiological 1049:1068 arg1 properties 1070:1079 electrophysiological properties 1049:1079 electrophysiological properties using DEP 1049:1089 We found NPs and APs are enriched in distinct fractions after separation by electrophysiological properties using DEP. 24105912 3 29 theme more 467:470 arg1 NPs 496:498 NPs 496:498 NPs 496:498 We found previously that populations of NSPCs with more neurogenic progenitors (NPs) can be distinguished from those with more astrogenic progenitors (APs) by their inherent biophysical properties, specifically the electrophysiological property of whole cell membrane capacitance, which we characterized with dielectrophoresis (DEP). 24105912 3 29 theme more 467:470 arg1 progenitors 483:493 more neurogenic progenitors 467:493 more neurogenic progenitors (NPs) 467:499 We found previously that populations of NSPCs with more neurogenic progenitors (NPs) can be distinguished from those with more astrogenic progenitors (APs) by their inherent biophysical properties, specifically the electrophysiological property of whole cell membrane capacitance, which we characterized with dielectrophoresis (DEP). 24105912 8 30 attach linked 1623:1628 arg2 properties 1457:1466 Inherent plasma membrane biophysical properties 1420:1466 Inherent plasma membrane biophysical properties 1420:1466 Inherent plasma membrane biophysical properties are thus sufficient to define progenitor cells of differing fate potential in the neural lineage, can be used to specifically isolate these cells, and are linked to patterns of glycosylation on the cell surface. 24105912 8 30 attach linked 1623:1628 arg1 patterns 1633:1640 patterns 1633:1640 patterns of glycosylation on the cell surface 1633:1677 Inherent plasma membrane biophysical properties are thus sufficient to define progenitor cells of differing fate potential in the neural lineage, can be used to specifically isolate these cells, and are linked to patterns of glycosylation on the cell surface. 24105912 8 31 theme fate 1528:1531 arg1 potential 1533:1541 differing fate potential 1518:1541 differing fate potential 1518:1541 Inherent plasma membrane biophysical properties are thus sufficient to define progenitor cells of differing fate potential in the neural lineage, can be used to specifically isolate these cells, and are linked to patterns of glycosylation on the cell surface. 24105912 8 32 theme biophysical 1445:1455 arg1 properties 1457:1466 Inherent plasma membrane biophysical properties 1420:1466 Inherent plasma membrane biophysical properties 1420:1466 Inherent plasma membrane biophysical properties are thus sufficient to define progenitor cells of differing fate potential in the neural lineage, can be used to specifically isolate these cells, and are linked to patterns of glycosylation on the cell surface. 24105912 1 33 theme progenitor 99:108 arg1 stem 90:93 Neural stem and progenitor cells 83:114 stem 90:93 Neural stem and progenitor cells (NSPCs) are heterogeneous populations of self-renewing stem cells and more committed progenitors that differentiate into neurons, astrocytes, and oligodendrocytes. 24105912 1 33 theme progenitor 99:108 arg1 cells 110:114 Neural stem and progenitor cells 83:114 cells 110:114 Neural stem and progenitor cells (NSPCs) are heterogeneous populations of self-renewing stem cells and more committed progenitors that differentiate into neurons, astrocytes, and oligodendrocytes. 24105912 1 33 theme progenitor 99:108 arg1 populations 142:152 heterogeneous populations 128:152 heterogeneous populations of self-renewing stem cells and more committed progenitors that differentiate into neurons, astrocytes, and oligodendrocytes 128:277 Neural stem and progenitor cells (NSPCs) are heterogeneous populations of self-renewing stem cells and more committed progenitors that differentiate into neurons, astrocytes, and oligodendrocytes. 24105912 5 34 from fractions 1019:1027 arg1 enriched 998:1005 enriched 998:1005 enriched 998:1005 We found NPs and APs are enriched in distinct fractions after separation by electrophysiological properties using DEP. 24105912 1 35 theme committed 191:199 arg1 progenitors 201:211 more committed progenitors 186:211 more committed progenitors 186:211 Neural stem and progenitor cells (NSPCs) are heterogeneous populations of self-renewing stem cells and more committed progenitors that differentiate into neurons, astrocytes, and oligodendrocytes. 24105912 0 36 theme astrocyte 38:46 arg1 progenitors 48:58 astrocyte progenitors 38:58 astrocyte progenitors 38:58 Membrane biophysics define neuron and astrocyte progenitors in the neural lineage. 24105912 8 37 from glycosylation 1645:1657 arg1 surface 1671:1677 the cell surface 1662:1677 the cell surface 1662:1677 Inherent plasma membrane biophysical properties are thus sufficient to define progenitor cells of differing fate potential in the neural lineage, can be used to specifically isolate these cells, and are linked to patterns of glycosylation on the cell surface. 24105912 3 38 theme NSPCs 456:460 arg1 populations 441:451 populations 441:451 populations of NSPCs with more neurogenic progenitors (NPs) 441:499 We found previously that populations of NSPCs with more neurogenic progenitors (NPs) can be distinguished from those with more astrogenic progenitors (APs) by their inherent biophysical properties, specifically the electrophysiological property of whole cell membrane capacitance, which we characterized with dielectrophoresis (DEP). 24105912 3 39 theme inherent 581:588 arg1 properties 602:611 their inherent biophysical properties 575:611 their inherent biophysical properties 575:611 We found previously that populations of NSPCs with more neurogenic progenitors (NPs) can be distinguished from those with more astrogenic progenitors (APs) by their inherent biophysical properties, specifically the electrophysiological property of whole cell membrane capacitance, which we characterized with dielectrophoresis (DEP). 24105912 7 40 theme molecular 1365:1373 arg1 basis 1375:1379 a molecular basis 1363:1379 a molecular basis for the cell membrane characteristics 1363:1417 Additionally, cell surface N-linked glycosylation was found to significantly affect cell fate-specific electrophysiological properties, providing a molecular basis for the cell membrane characteristics. 24105912 1 41 theme progenitors 201:211 arg1 stem 90:93 Neural stem and progenitor cells 83:114 stem 90:93 Neural stem and progenitor cells (NSPCs) are heterogeneous populations of self-renewing stem cells and more committed progenitors that differentiate into neurons, astrocytes, and oligodendrocytes. 24105912 1 41 theme progenitors 201:211 arg1 cells 110:114 Neural stem and progenitor cells 83:114 cells 110:114 Neural stem and progenitor cells (NSPCs) are heterogeneous populations of self-renewing stem cells and more committed progenitors that differentiate into neurons, astrocytes, and oligodendrocytes. 24105912 1 41 theme progenitors 201:211 arg1 populations 142:152 heterogeneous populations 128:152 heterogeneous populations of self-renewing stem cells and more committed progenitors that differentiate into neurons, astrocytes, and oligodendrocytes 128:277 Neural stem and progenitor cells (NSPCs) are heterogeneous populations of self-renewing stem cells and more committed progenitors that differentiate into neurons, astrocytes, and oligodendrocytes. 24105912 7 42 gly glycosylation 1253:1265 arg1 electrophysiological 1320:1339 cell fate-specific electrophysiological properties 1301:1350 cell fate-specific electrophysiological properties 1301:1350 Additionally, cell surface N-linked glycosylation was found to significantly affect cell fate-specific electrophysiological properties, providing a molecular basis for the cell membrane characteristics. 24105912 7 42 gly glycosylation 1253:1265 arg1 cell 1301:1304 cell fate-specific electrophysiological properties 1301:1350 cell fate-specific electrophysiological properties 1301:1350 Additionally, cell surface N-linked glycosylation was found to significantly affect cell fate-specific electrophysiological properties, providing a molecular basis for the cell membrane characteristics. 24105912 3 43 theme electrophysiological 631:650 arg1 property 652:659 the electrophysiological property 627:659 the electrophysiological property of whole cell membrane capacitance 627:694 We found previously that populations of NSPCs with more neurogenic progenitors (NPs) can be distinguished from those with more astrogenic progenitors (APs) by their inherent biophysical properties, specifically the electrophysiological property of whole cell membrane capacitance, which we characterized with dielectrophoresis (DEP). 24105912 3 44 theme biophysical 590:600 arg1 properties 602:611 their inherent biophysical properties 575:611 their inherent biophysical properties 575:611 We found previously that populations of NSPCs with more neurogenic progenitors (NPs) can be distinguished from those with more astrogenic progenitors (APs) by their inherent biophysical properties, specifically the electrophysiological property of whole cell membrane capacitance, which we characterized with dielectrophoresis (DEP). 24105912 8 45 theme Inherent 1420:1427 arg1 properties 1457:1466 Inherent plasma membrane biophysical properties 1420:1466 Inherent plasma membrane biophysical properties 1420:1466 Inherent plasma membrane biophysical properties are thus sufficient to define progenitor cells of differing fate potential in the neural lineage, can be used to specifically isolate these cells, and are linked to patterns of glycosylation on the cell surface. 24105912 8 46 theme differing 1518:1526 arg1 potential 1533:1541 differing fate potential 1518:1541 differing fate potential 1518:1541 Inherent plasma membrane biophysical properties are thus sufficient to define progenitor cells of differing fate potential in the neural lineage, can be used to specifically isolate these cells, and are linked to patterns of glycosylation on the cell surface. 24105912 7 47 theme cell 1301:1304 arg1 properties 1341:1350 cell fate-specific electrophysiological properties 1301:1350 cell fate-specific electrophysiological properties 1301:1350 Additionally, cell surface N-linked glycosylation was found to significantly affect cell fate-specific electrophysiological properties, providing a molecular basis for the cell membrane characteristics. 24105912 4 48 theme cells 904:908 arg1 isolation 891:899 isolation 891:899 isolation of cells solely by these properties 891:935 Here, we hypothesize that inherent electrophysiological properties are sufficient to define NPs and APs and test this by determining whether isolation of cells solely by these properties specifically separates NPs and APs. 24105912 3 49 theme capacitance 684:694 arg1 property 652:659 the electrophysiological property 627:659 the electrophysiological property of whole cell membrane capacitance 627:694 We found previously that populations of NSPCs with more neurogenic progenitors (NPs) can be distinguished from those with more astrogenic progenitors (APs) by their inherent biophysical properties, specifically the electrophysiological property of whole cell membrane capacitance, which we characterized with dielectrophoresis (DEP). 24105912 7 50 theme fate-specific 1306:1318 arg1 properties 1341:1350 cell fate-specific electrophysiological properties 1301:1350 cell fate-specific electrophysiological properties 1301:1350 Additionally, cell surface N-linked glycosylation was found to significantly affect cell fate-specific electrophysiological properties, providing a molecular basis for the cell membrane characteristics. 24105912 6 51 theme NP 1206:1207 arg1 marker 1209:1214 an NP marker 1203:1214 an NP marker 1203:1214 A single round of DEP isolation provided greater NP enrichment than sorting with PSA-NCAM, which is considered an NP marker. 24105912 8 52 from surface 1671:1677 arg1 patterns 1633:1640 patterns 1633:1640 patterns of glycosylation on the cell surface 1633:1677 Inherent plasma membrane biophysical properties are thus sufficient to define progenitor cells of differing fate potential in the neural lineage, can be used to specifically isolate these cells, and are linked to patterns of glycosylation on the cell surface. 24105912 8 53 theme potential 1533:1541 arg1 cells 1509:1513 progenitor cells 1498:1513 progenitor cells of differing fate potential in the neural lineage 1498:1563 Inherent plasma membrane biophysical properties are thus sufficient to define progenitor cells of differing fate potential in the neural lineage, can be used to specifically isolate these cells, and are linked to patterns of glycosylation on the cell surface. 24105912 7 54 theme membrane 1394:1401 arg1 characteristics 1403:1417 the cell membrane characteristics 1385:1417 the cell membrane characteristics 1385:1417 Additionally, cell surface N-linked glycosylation was found to significantly affect cell fate-specific electrophysiological properties, providing a molecular basis for the cell membrane characteristics. 24105912 8 55 gly glycosylation 1645:1657 arg1 surface 1671:1677 the cell surface 1662:1677 the cell surface 1662:1677 Inherent plasma membrane biophysical properties are thus sufficient to define progenitor cells of differing fate potential in the neural lineage, can be used to specifically isolate these cells, and are linked to patterns of glycosylation on the cell surface. 24105912 8 56 theme membrane 1436:1443 arg1 properties 1457:1466 Inherent plasma membrane biophysical properties 1420:1466 Inherent plasma membrane biophysical properties 1420:1466 Inherent plasma membrane biophysical properties are thus sufficient to define progenitor cells of differing fate potential in the neural lineage, can be used to specifically isolate these cells, and are linked to patterns of glycosylation on the cell surface. 24105912 8 57 theme glycosylation 1645:1657 arg1 patterns 1633:1640 patterns 1633:1640 patterns of glycosylation on the cell surface 1633:1677 Inherent plasma membrane biophysical properties are thus sufficient to define progenitor cells of differing fate potential in the neural lineage, can be used to specifically isolate these cells, and are linked to patterns of glycosylation on the cell surface. 24105912 3 58 theme cell 670:673 arg1 capacitance 684:694 whole cell membrane capacitance 664:694 whole cell membrane capacitance 664:694 We found previously that populations of NSPCs with more neurogenic progenitors (NPs) can be distinguished from those with more astrogenic progenitors (APs) by their inherent biophysical properties, specifically the electrophysiological property of whole cell membrane capacitance, which we characterized with dielectrophoresis (DEP). 24105912 6 59 dep greater 1133:1139 arg1 enrichment 1144:1153 NP enrichment 1141:1153 NP enrichment 1141:1153 A single round of DEP isolation provided greater NP enrichment than sorting with PSA-NCAM, which is considered an NP marker. 24105912 5 60 dep NPs 982:984 arg1 enriched 998:1005 enriched 998:1005 enriched 998:1005 We found NPs and APs are enriched in distinct fractions after separation by electrophysiological properties using DEP. 24105912 0 61 theme neural 67:72 arg1 lineage 74:80 the neural lineage 63:80 the neural lineage 63:80 Membrane biophysics define neuron and astrocyte progenitors in the neural lineage. 24105912 3 62 theme membrane 675:682 arg1 capacitance 684:694 whole cell membrane capacitance 664:694 whole cell membrane capacitance 664:694 We found previously that populations of NSPCs with more neurogenic progenitors (NPs) can be distinguished from those with more astrogenic progenitors (APs) by their inherent biophysical properties, specifically the electrophysiological property of whole cell membrane capacitance, which we characterized with dielectrophoresis (DEP). 24105912 8 63 theme progenitor 1498:1507 arg1 cells 1509:1513 progenitor cells 1498:1513 progenitor cells of differing fate potential in the neural lineage 1498:1563 Inherent plasma membrane biophysical properties are thus sufficient to define progenitor cells of differing fate potential in the neural lineage, can be used to specifically isolate these cells, and are linked to patterns of glycosylation on the cell surface. 24105912 3 64 dep properties 602:611 arg1 property 652:659 the electrophysiological property 627:659 the electrophysiological property of whole cell membrane capacitance 627:694 We found previously that populations of NSPCs with more neurogenic progenitors (NPs) can be distinguished from those with more astrogenic progenitors (APs) by their inherent biophysical properties, specifically the electrophysiological property of whole cell membrane capacitance, which we characterized with dielectrophoresis (DEP). 24105912 6 65 theme single 1094:1099 arg1 round 1101:1105 A single round 1092:1105 A single round of DEP isolation 1092:1122 A single round of DEP isolation provided greater NP enrichment than sorting with PSA-NCAM, which is considered an NP marker. 24105912 7 66 theme N-linked 1244:1251 arg1 glycosylation 1253:1265 cell surface N-linked glycosylation 1231:1265 cell surface N-linked glycosylation 1231:1265 Additionally, cell surface N-linked glycosylation was found to significantly affect cell fate-specific electrophysiological properties, providing a molecular basis for the cell membrane characteristics. 24105912 0 67 from neuron 27:32 arg1 lineage 74:80 the neural lineage 63:80 the neural lineage 63:80 Membrane biophysics define neuron and astrocyte progenitors in the neural lineage. 24105912 5 68 theme distinct 1010:1017 arg1 fractions 1019:1027 distinct fractions 1010:1027 distinct fractions after separation by electrophysiological properties using DEP 1010:1089 We found NPs and APs are enriched in distinct fractions after separation by electrophysiological properties using DEP. 24105912 1 69 theme heterogeneous 128:140 arg1 stem 90:93 Neural stem and progenitor cells 83:114 stem 90:93 Neural stem and progenitor cells (NSPCs) are heterogeneous populations of self-renewing stem cells and more committed progenitors that differentiate into neurons, astrocytes, and oligodendrocytes. 24105912 1 69 theme heterogeneous 128:140 arg1 cells 110:114 Neural stem and progenitor cells 83:114 cells 110:114 Neural stem and progenitor cells (NSPCs) are heterogeneous populations of self-renewing stem cells and more committed progenitors that differentiate into neurons, astrocytes, and oligodendrocytes. 24105912 1 69 theme heterogeneous 128:140 arg1 populations 142:152 heterogeneous populations 128:152 heterogeneous populations of self-renewing stem cells and more committed progenitors that differentiate into neurons, astrocytes, and oligodendrocytes 128:277 Neural stem and progenitor cells (NSPCs) are heterogeneous populations of self-renewing stem cells and more committed progenitors that differentiate into neurons, astrocytes, and oligodendrocytes. 28765562 3 0 from performance 695:705 arg1 enrichment 723:732 glycopeptide enrichment 710:732 glycopeptide enrichment with high detection sensitivity (10 fmol), large binding capacity (100 μg mg-1) and satisfied enrichment recovery (approximately 82%) 710:866 Owing to the excellent hydrophilicity and strong electrostatic interaction toward glycopeptides of the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride (MAC), the synthesized Fe3O4@MPS@PMAC nanoparticles exhibited outstanding performance in glycopeptide enrichment with high detection sensitivity (10 fmol), large binding capacity (100 μg mg-1) and satisfied enrichment recovery (approximately 82%). 28765562 3 1 theme high 739:742 arg1 sensitivity 754:764 high detection sensitivity 739:764 high detection sensitivity (10 fmol) 739:774 Owing to the excellent hydrophilicity and strong electrostatic interaction toward glycopeptides of the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride (MAC), the synthesized Fe3O4@MPS@PMAC nanoparticles exhibited outstanding performance in glycopeptide enrichment with high detection sensitivity (10 fmol), large binding capacity (100 μg mg-1) and satisfied enrichment recovery (approximately 82%). 28765562 3 1 theme high 739:742 arg1 fmol 770:773 10 fmol 767:773 10 fmol 767:773 Owing to the excellent hydrophilicity and strong electrostatic interaction toward glycopeptides of the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride (MAC), the synthesized Fe3O4@MPS@PMAC nanoparticles exhibited outstanding performance in glycopeptide enrichment with high detection sensitivity (10 fmol), large binding capacity (100 μg mg-1) and satisfied enrichment recovery (approximately 82%). 28765562 4 2 theme MPS 908:910 arg1 nanoparticles 917:929 the newly developed Fe3O4@MPS@PMAC nanoparticles 882:929 the newly developed Fe3O4@MPS@PMAC nanoparticles 882:929 Furthermore, the newly developed Fe3O4@MPS@PMAC nanoparticles were applied for the glycopeptide enrichment of HeLa exosome proteins. 28765562 1 3 theme glycopeptides 158:170 arg1 abundance 145:153 The low abundance 137:153 The low abundance of glycopeptides in biological samples 137:192 The low abundance of glycopeptides in biological samples makes it necessary to enrich them before further analysis. 28765562 3 4 with enrichment 723:732 arg1 sensitivity 754:764 high detection sensitivity 739:764 high detection sensitivity (10 fmol) 739:774 Owing to the excellent hydrophilicity and strong electrostatic interaction toward glycopeptides of the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride (MAC), the synthesized Fe3O4@MPS@PMAC nanoparticles exhibited outstanding performance in glycopeptide enrichment with high detection sensitivity (10 fmol), large binding capacity (100 μg mg-1) and satisfied enrichment recovery (approximately 82%). 28765562 3 4 with enrichment 723:732 arg1 % 865:865 approximately 82% 849:865 approximately 82% 849:865 Owing to the excellent hydrophilicity and strong electrostatic interaction toward glycopeptides of the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride (MAC), the synthesized Fe3O4@MPS@PMAC nanoparticles exhibited outstanding performance in glycopeptide enrichment with high detection sensitivity (10 fmol), large binding capacity (100 μg mg-1) and satisfied enrichment recovery (approximately 82%). 28765562 3 4 with enrichment 723:732 arg1 capacity 791:798 large binding capacity 777:798 large binding capacity (100 μg mg-1) 777:812 Owing to the excellent hydrophilicity and strong electrostatic interaction toward glycopeptides of the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride (MAC), the synthesized Fe3O4@MPS@PMAC nanoparticles exhibited outstanding performance in glycopeptide enrichment with high detection sensitivity (10 fmol), large binding capacity (100 μg mg-1) and satisfied enrichment recovery (approximately 82%). 28765562 3 4 with enrichment 723:732 arg1 recovery 839:846 satisfied enrichment recovery 818:846 satisfied enrichment recovery (approximately 82%) 818:866 Owing to the excellent hydrophilicity and strong electrostatic interaction toward glycopeptides of the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride (MAC), the synthesized Fe3O4@MPS@PMAC nanoparticles exhibited outstanding performance in glycopeptide enrichment with high detection sensitivity (10 fmol), large binding capacity (100 μg mg-1) and satisfied enrichment recovery (approximately 82%). 28765562 3 4 with enrichment 723:732 arg1 100 μg mg-1 801:811 100 μg mg-1 801:811 100 μg mg-1 801:811 Owing to the excellent hydrophilicity and strong electrostatic interaction toward glycopeptides of the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride (MAC), the synthesized Fe3O4@MPS@PMAC nanoparticles exhibited outstanding performance in glycopeptide enrichment with high detection sensitivity (10 fmol), large binding capacity (100 μg mg-1) and satisfied enrichment recovery (approximately 82%). 28765562 3 4 with enrichment 723:732 arg1 fmol 770:773 10 fmol 767:773 10 fmol 767:773 Owing to the excellent hydrophilicity and strong electrostatic interaction toward glycopeptides of the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride (MAC), the synthesized Fe3O4@MPS@PMAC nanoparticles exhibited outstanding performance in glycopeptide enrichment with high detection sensitivity (10 fmol), large binding capacity (100 μg mg-1) and satisfied enrichment recovery (approximately 82%). 28765562 4 5 theme exosome 984:990 arg1 proteins 992:999 HeLa exosome proteins 979:999 HeLa exosome proteins 979:999 Furthermore, the newly developed Fe3O4@MPS@PMAC nanoparticles were applied for the glycopeptide enrichment of HeLa exosome proteins. 28765562 3 6 theme glycopeptide 710:721 arg1 enrichment 723:732 glycopeptide enrichment 710:732 glycopeptide enrichment with high detection sensitivity (10 fmol), large binding capacity (100 μg mg-1) and satisfied enrichment recovery (approximately 82%) 710:866 Owing to the excellent hydrophilicity and strong electrostatic interaction toward glycopeptides of the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride (MAC), the synthesized Fe3O4@MPS@PMAC nanoparticles exhibited outstanding performance in glycopeptide enrichment with high detection sensitivity (10 fmol), large binding capacity (100 μg mg-1) and satisfied enrichment recovery (approximately 82%). 28765562 3 7 theme ionic 552:556 arg1 MAC 622:624 MAC 622:624 MAC 622:624 Owing to the excellent hydrophilicity and strong electrostatic interaction toward glycopeptides of the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride (MAC), the synthesized Fe3O4@MPS@PMAC nanoparticles exhibited outstanding performance in glycopeptide enrichment with high detection sensitivity (10 fmol), large binding capacity (100 μg mg-1) and satisfied enrichment recovery (approximately 82%). 28765562 3 7 theme ionic 552:556 arg1 chloride 612:619 the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride 524:619 chloride 612:619 Owing to the excellent hydrophilicity and strong electrostatic interaction toward glycopeptides of the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride (MAC), the synthesized Fe3O4@MPS@PMAC nanoparticles exhibited outstanding performance in glycopeptide enrichment with high detection sensitivity (10 fmol), large binding capacity (100 μg mg-1) and satisfied enrichment recovery (approximately 82%). 28765562 4 8 theme PMAC 912:915 arg1 nanoparticles 917:929 the newly developed Fe3O4@MPS@PMAC nanoparticles 882:929 the newly developed Fe3O4@MPS@PMAC nanoparticles 882:929 Furthermore, the newly developed Fe3O4@MPS@PMAC nanoparticles were applied for the glycopeptide enrichment of HeLa exosome proteins. 28765562 4 9 theme developed 892:900 arg1 nanoparticles 917:929 the newly developed Fe3O4@MPS@PMAC nanoparticles 882:929 the newly developed Fe3O4@MPS@PMAC nanoparticles 882:929 Furthermore, the newly developed Fe3O4@MPS@PMAC nanoparticles were applied for the glycopeptide enrichment of HeLa exosome proteins. 28765562 6 10 theme Fe3O4 1177:1181 arg1 nanoparticles 1192:1204 Fe3O4@MPS@PMAC nanoparticles 1177:1204 Fe3O4@MPS@PMAC nanoparticles 1177:1204 These results demonstrate the potential of Fe3O4@MPS@PMAC nanoparticles for both glycoproteomic analysis and exosome research. 28765562 3 11 theme methacryloyloxy 570:584 arg1 MAC 622:624 MAC 622:624 MAC 622:624 Owing to the excellent hydrophilicity and strong electrostatic interaction toward glycopeptides of the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride (MAC), the synthesized Fe3O4@MPS@PMAC nanoparticles exhibited outstanding performance in glycopeptide enrichment with high detection sensitivity (10 fmol), large binding capacity (100 μg mg-1) and satisfied enrichment recovery (approximately 82%). 28765562 3 11 theme methacryloyloxy 570:584 arg1 chloride 612:619 the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride 524:619 chloride 612:619 Owing to the excellent hydrophilicity and strong electrostatic interaction toward glycopeptides of the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride (MAC), the synthesized Fe3O4@MPS@PMAC nanoparticles exhibited outstanding performance in glycopeptide enrichment with high detection sensitivity (10 fmol), large binding capacity (100 μg mg-1) and satisfied enrichment recovery (approximately 82%). 28765562 0 12 theme selective 89:97 arg1 enrichment 99:108 the highly selective enrichment 78:108 the highly selective enrichment of N-linked glycopeptides 78:134 Polymeric hydrophilic ionic liquids used to modify magnetic nanoparticles for the highly selective enrichment of N-linked glycopeptides. 28765562 5 13 theme 50 μg 1102:1106 arg1 analyses 1090:1097 three replicate analyses 1074:1097 three replicate analyses of 50 μg of HeLa exosome proteins 1074:1131 A total of 1274 glycopeptides from 536 glycoproteins were identified in three replicate analyses of 50 μg of HeLa exosome proteins. 28765562 6 14 theme MPS 1183:1185 arg1 nanoparticles 1192:1204 Fe3O4@MPS@PMAC nanoparticles 1177:1204 Fe3O4@MPS@PMAC nanoparticles 1177:1204 These results demonstrate the potential of Fe3O4@MPS@PMAC nanoparticles for both glycoproteomic analysis and exosome research. 28765562 1 15 from abundance 145:153 arg1 samples 186:192 biological samples 175:192 biological samples 175:192 The low abundance of glycopeptides in biological samples makes it necessary to enrich them before further analysis. 28765562 3 16 theme hydrophilic 540:550 arg1 MAC 622:624 MAC 622:624 MAC 622:624 Owing to the excellent hydrophilicity and strong electrostatic interaction toward glycopeptides of the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride (MAC), the synthesized Fe3O4@MPS@PMAC nanoparticles exhibited outstanding performance in glycopeptide enrichment with high detection sensitivity (10 fmol), large binding capacity (100 μg mg-1) and satisfied enrichment recovery (approximately 82%). 28765562 3 16 theme hydrophilic 540:550 arg1 chloride 612:619 the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride 524:619 chloride 612:619 Owing to the excellent hydrophilicity and strong electrostatic interaction toward glycopeptides of the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride (MAC), the synthesized Fe3O4@MPS@PMAC nanoparticles exhibited outstanding performance in glycopeptide enrichment with high detection sensitivity (10 fmol), large binding capacity (100 μg mg-1) and satisfied enrichment recovery (approximately 82%). 28765562 5 17 from glycoproteins 1041:1053 arg1 total 1004:1008 A total 1002:1008 A total of 1274 glycopeptides from 536 glycoproteins 1002:1053 A total of 1274 glycopeptides from 536 glycoproteins were identified in three replicate analyses of 50 μg of HeLa exosome proteins. 28765562 5 17 from glycoproteins 1041:1053 arg1 glycopeptides 1018:1030 1274 glycopeptides 1013:1030 1274 glycopeptides from 536 glycoproteins 1013:1053 A total of 1274 glycopeptides from 536 glycoproteins were identified in three replicate analyses of 50 μg of HeLa exosome proteins. 28765562 2 18 theme @ 331:331 arg1 magnetic 316:323 magnetic 316:323 magnetic 316:323 In this study, the polymeric hydrophilic ionic liquid-modified magnetic (Fe3O4@MPS@PMAC) nanoparticles were synthesized via a one-step reflux-precipitation polymerization. 28765562 2 18 theme @ 331:331 arg1 PMAC 336:339 Fe3O4@MPS@PMAC 326:339 Fe3O4@MPS@PMAC 326:339 In this study, the polymeric hydrophilic ionic liquid-modified magnetic (Fe3O4@MPS@PMAC) nanoparticles were synthesized via a one-step reflux-precipitation polymerization. 28765562 0 19 theme N-linked 113:120 arg1 glycopeptides 122:134 N-linked glycopeptides 113:134 N-linked glycopeptides 113:134 Polymeric hydrophilic ionic liquids used to modify magnetic nanoparticles for the highly selective enrichment of N-linked glycopeptides. 28765562 5 20 from total 1004:1008 arg1 glycoproteins 1041:1053 536 glycoproteins 1037:1053 536 glycoproteins 1037:1053 A total of 1274 glycopeptides from 536 glycoproteins were identified in three replicate analyses of 50 μg of HeLa exosome proteins. 28765562 5 21 gly glycoproteins 1041:1053 arg1 glycoproteins 1041:1053 536 glycoproteins 1037:1053 536 glycoproteins 1037:1053 A total of 1274 glycopeptides from 536 glycoproteins were identified in three replicate analyses of 50 μg of HeLa exosome proteins. 28765562 6 22 theme @ 1182:1182 arg1 nanoparticles 1192:1204 Fe3O4@MPS@PMAC nanoparticles 1177:1204 Fe3O4@MPS@PMAC nanoparticles 1177:1204 These results demonstrate the potential of Fe3O4@MPS@PMAC nanoparticles for both glycoproteomic analysis and exosome research. 28765562 1 23 theme biological 175:184 arg1 samples 186:192 biological samples 175:192 biological samples 175:192 The low abundance of glycopeptides in biological samples makes it necessary to enrich them before further analysis. 28765562 4 24 theme glycopeptide 952:963 arg1 enrichment 965:974 the glycopeptide enrichment 948:974 the glycopeptide enrichment of HeLa exosome proteins 948:999 Furthermore, the newly developed Fe3O4@MPS@PMAC nanoparticles were applied for the glycopeptide enrichment of HeLa exosome proteins. 28765562 0 25 used used 36:39 arg2 liquids 28:34 Polymeric hydrophilic ionic liquids 0:34 Polymeric hydrophilic ionic liquids 0:34 Polymeric hydrophilic ionic liquids used to modify magnetic nanoparticles for the highly selective enrichment of N-linked glycopeptides. 28765562 5 26 theme proteins 1124:1131 arg1 50 μg 1102:1106 50 μg 1102:1106 50 μg of HeLa exosome proteins 1102:1131 A total of 1274 glycopeptides from 536 glycoproteins were identified in three replicate analyses of 50 μg of HeLa exosome proteins. 28765562 3 27 theme enrichment 828:837 arg1 % 865:865 approximately 82% 849:865 approximately 82% 849:865 Owing to the excellent hydrophilicity and strong electrostatic interaction toward glycopeptides of the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride (MAC), the synthesized Fe3O4@MPS@PMAC nanoparticles exhibited outstanding performance in glycopeptide enrichment with high detection sensitivity (10 fmol), large binding capacity (100 μg mg-1) and satisfied enrichment recovery (approximately 82%). 28765562 3 27 theme enrichment 828:837 arg1 recovery 839:846 satisfied enrichment recovery 818:846 satisfied enrichment recovery (approximately 82%) 818:866 Owing to the excellent hydrophilicity and strong electrostatic interaction toward glycopeptides of the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride (MAC), the synthesized Fe3O4@MPS@PMAC nanoparticles exhibited outstanding performance in glycopeptide enrichment with high detection sensitivity (10 fmol), large binding capacity (100 μg mg-1) and satisfied enrichment recovery (approximately 82%). 28765562 2 28 theme one-step 379:386 arg1 polymerization 409:422 a one-step reflux-precipitation polymerization 377:422 a one-step reflux-precipitation polymerization 377:422 In this study, the polymeric hydrophilic ionic liquid-modified magnetic (Fe3O4@MPS@PMAC) nanoparticles were synthesized via a one-step reflux-precipitation polymerization. 28765562 0 29 theme hydrophilic 10:20 arg1 liquids 28:34 Polymeric hydrophilic ionic liquids 0:34 Polymeric hydrophilic ionic liquids 0:34 Polymeric hydrophilic ionic liquids used to modify magnetic nanoparticles for the highly selective enrichment of N-linked glycopeptides. 28765562 5 30 theme exosome 1116:1122 arg1 proteins 1124:1131 HeLa exosome proteins 1111:1131 HeLa exosome proteins 1111:1131 A total of 1274 glycopeptides from 536 glycoproteins were identified in three replicate analyses of 50 μg of HeLa exosome proteins. 28765562 5 31 dep analyses 1090:1097 arg1 replicate 1080:1088 replicate 1080:1088 replicate 1080:1088 A total of 1274 glycopeptides from 536 glycoproteins were identified in three replicate analyses of 50 μg of HeLa exosome proteins. 28765562 2 32 theme Fe3O4 326:330 arg1 magnetic 316:323 magnetic 316:323 magnetic 316:323 In this study, the polymeric hydrophilic ionic liquid-modified magnetic (Fe3O4@MPS@PMAC) nanoparticles were synthesized via a one-step reflux-precipitation polymerization. 28765562 2 32 theme Fe3O4 326:330 arg1 PMAC 336:339 Fe3O4@MPS@PMAC 326:339 Fe3O4@MPS@PMAC 326:339 In this study, the polymeric hydrophilic ionic liquid-modified magnetic (Fe3O4@MPS@PMAC) nanoparticles were synthesized via a one-step reflux-precipitation polymerization. 28765562 0 33 theme Polymeric 0:8 arg1 liquids 28:34 Polymeric hydrophilic ionic liquids 0:34 Polymeric hydrophilic ionic liquids 0:34 Polymeric hydrophilic ionic liquids used to modify magnetic nanoparticles for the highly selective enrichment of N-linked glycopeptides. 28765562 3 34 theme chloride 612:619 arg1 hydrophilicity 448:461 the excellent hydrophilicity 434:461 the excellent hydrophilicity 434:461 Owing to the excellent hydrophilicity and strong electrostatic interaction toward glycopeptides of the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride (MAC), the synthesized Fe3O4@MPS@PMAC nanoparticles exhibited outstanding performance in glycopeptide enrichment with high detection sensitivity (10 fmol), large binding capacity (100 μg mg-1) and satisfied enrichment recovery (approximately 82%). 28765562 3 34 theme chloride 612:619 arg1 interaction 488:498 strong electrostatic interaction 467:498 strong electrostatic interaction 467:498 Owing to the excellent hydrophilicity and strong electrostatic interaction toward glycopeptides of the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride (MAC), the synthesized Fe3O4@MPS@PMAC nanoparticles exhibited outstanding performance in glycopeptide enrichment with high detection sensitivity (10 fmol), large binding capacity (100 μg mg-1) and satisfied enrichment recovery (approximately 82%). 28765562 3 35 theme excellent 438:446 arg1 hydrophilicity 448:461 the excellent hydrophilicity 434:461 the excellent hydrophilicity 434:461 Owing to the excellent hydrophilicity and strong electrostatic interaction toward glycopeptides of the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride (MAC), the synthesized Fe3O4@MPS@PMAC nanoparticles exhibited outstanding performance in glycopeptide enrichment with high detection sensitivity (10 fmol), large binding capacity (100 μg mg-1) and satisfied enrichment recovery (approximately 82%). 28765562 3 36 theme large 777:781 arg1 capacity 791:798 large binding capacity 777:798 large binding capacity (100 μg mg-1) 777:812 Owing to the excellent hydrophilicity and strong electrostatic interaction toward glycopeptides of the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride (MAC), the synthesized Fe3O4@MPS@PMAC nanoparticles exhibited outstanding performance in glycopeptide enrichment with high detection sensitivity (10 fmol), large binding capacity (100 μg mg-1) and satisfied enrichment recovery (approximately 82%). 28765562 3 36 theme large 777:781 arg1 100 μg mg-1 801:811 100 μg mg-1 801:811 100 μg mg-1 801:811 Owing to the excellent hydrophilicity and strong electrostatic interaction toward glycopeptides of the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride (MAC), the synthesized Fe3O4@MPS@PMAC nanoparticles exhibited outstanding performance in glycopeptide enrichment with high detection sensitivity (10 fmol), large binding capacity (100 μg mg-1) and satisfied enrichment recovery (approximately 82%). 28765562 3 37 theme trimethylammonium 594:610 arg1 MAC 622:624 MAC 622:624 MAC 622:624 Owing to the excellent hydrophilicity and strong electrostatic interaction toward glycopeptides of the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride (MAC), the synthesized Fe3O4@MPS@PMAC nanoparticles exhibited outstanding performance in glycopeptide enrichment with high detection sensitivity (10 fmol), large binding capacity (100 μg mg-1) and satisfied enrichment recovery (approximately 82%). 28765562 3 37 theme trimethylammonium 594:610 arg1 chloride 612:619 the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride 524:619 chloride 612:619 Owing to the excellent hydrophilicity and strong electrostatic interaction toward glycopeptides of the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride (MAC), the synthesized Fe3O4@MPS@PMAC nanoparticles exhibited outstanding performance in glycopeptide enrichment with high detection sensitivity (10 fmol), large binding capacity (100 μg mg-1) and satisfied enrichment recovery (approximately 82%). 28765562 2 38 theme magnetic 316:323 arg1 nanoparticles 342:354 the polymeric hydrophilic ionic liquid-modified magnetic (Fe3O4@MPS@PMAC) nanoparticles 268:354 the polymeric hydrophilic ionic liquid-modified magnetic (Fe3O4@MPS@PMAC) nanoparticles 268:354 In this study, the polymeric hydrophilic ionic liquid-modified magnetic (Fe3O4@MPS@PMAC) nanoparticles were synthesized via a one-step reflux-precipitation polymerization. 28765562 6 39 theme exosome 1243:1249 arg1 research 1251:1258 exosome research 1243:1258 exosome research 1243:1258 These results demonstrate the potential of Fe3O4@MPS@PMAC nanoparticles for both glycoproteomic analysis and exosome research. 28765562 0 40 theme ionic 22:26 arg1 liquids 28:34 Polymeric hydrophilic ionic liquids 0:34 Polymeric hydrophilic ionic liquids 0:34 Polymeric hydrophilic ionic liquids used to modify magnetic nanoparticles for the highly selective enrichment of N-linked glycopeptides. 28765562 6 41 theme @ 1186:1186 arg1 nanoparticles 1192:1204 Fe3O4@MPS@PMAC nanoparticles 1177:1204 Fe3O4@MPS@PMAC nanoparticles 1177:1204 These results demonstrate the potential of Fe3O4@MPS@PMAC nanoparticles for both glycoproteomic analysis and exosome research. 28765562 0 42 theme glycopeptides 122:134 arg1 enrichment 99:108 the highly selective enrichment 78:108 the highly selective enrichment of N-linked glycopeptides 78:134 Polymeric hydrophilic ionic liquids used to modify magnetic nanoparticles for the highly selective enrichment of N-linked glycopeptides. 28765562 3 43 theme PMAC 654:657 arg1 nanoparticles 659:671 the synthesized Fe3O4@MPS@PMAC nanoparticles 628:671 the synthesized Fe3O4@MPS@PMAC nanoparticles 628:671 Owing to the excellent hydrophilicity and strong electrostatic interaction toward glycopeptides of the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride (MAC), the synthesized Fe3O4@MPS@PMAC nanoparticles exhibited outstanding performance in glycopeptide enrichment with high detection sensitivity (10 fmol), large binding capacity (100 μg mg-1) and satisfied enrichment recovery (approximately 82%). 28765562 3 44 gly glycopeptides 507:519 arg2 glycopeptides 507:519 glycopeptides 507:519 glycopeptides 507:519 Owing to the excellent hydrophilicity and strong electrostatic interaction toward glycopeptides of the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride (MAC), the synthesized Fe3O4@MPS@PMAC nanoparticles exhibited outstanding performance in glycopeptide enrichment with high detection sensitivity (10 fmol), large binding capacity (100 μg mg-1) and satisfied enrichment recovery (approximately 82%). 28765562 3 45 dep chloride 612:619 arg1 [2- 566:568 the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride 524:619 [2- 566:568 Owing to the excellent hydrophilicity and strong electrostatic interaction toward glycopeptides of the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride (MAC), the synthesized Fe3O4@MPS@PMAC nanoparticles exhibited outstanding performance in glycopeptide enrichment with high detection sensitivity (10 fmol), large binding capacity (100 μg mg-1) and satisfied enrichment recovery (approximately 82%). 28765562 3 46 theme polymerized 528:538 arg1 MAC 622:624 MAC 622:624 MAC 622:624 Owing to the excellent hydrophilicity and strong electrostatic interaction toward glycopeptides of the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride (MAC), the synthesized Fe3O4@MPS@PMAC nanoparticles exhibited outstanding performance in glycopeptide enrichment with high detection sensitivity (10 fmol), large binding capacity (100 μg mg-1) and satisfied enrichment recovery (approximately 82%). 28765562 3 46 theme polymerized 528:538 arg1 chloride 612:619 the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride 524:619 chloride 612:619 Owing to the excellent hydrophilicity and strong electrostatic interaction toward glycopeptides of the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride (MAC), the synthesized Fe3O4@MPS@PMAC nanoparticles exhibited outstanding performance in glycopeptide enrichment with high detection sensitivity (10 fmol), large binding capacity (100 μg mg-1) and satisfied enrichment recovery (approximately 82%). 28765562 5 47 theme 1274 1013:1016 arg1 glycopeptides 1018:1030 1274 glycopeptides 1013:1030 1274 glycopeptides from 536 glycoproteins 1013:1053 A total of 1274 glycopeptides from 536 glycoproteins were identified in three replicate analyses of 50 μg of HeLa exosome proteins. 28765562 4 48 gly glycopeptide 952:963 arg2 glycopeptide 952:963 glycopeptide 952:963 glycopeptide 952:963 Furthermore, the newly developed Fe3O4@MPS@PMAC nanoparticles were applied for the glycopeptide enrichment of HeLa exosome proteins. 28765562 3 49 theme strong 467:472 arg1 interaction 488:498 strong electrostatic interaction 467:498 strong electrostatic interaction 467:498 Owing to the excellent hydrophilicity and strong electrostatic interaction toward glycopeptides of the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride (MAC), the synthesized Fe3O4@MPS@PMAC nanoparticles exhibited outstanding performance in glycopeptide enrichment with high detection sensitivity (10 fmol), large binding capacity (100 μg mg-1) and satisfied enrichment recovery (approximately 82%). 28765562 2 50 theme reflux-precipitation 388:407 arg1 polymerization 409:422 a one-step reflux-precipitation polymerization 377:422 a one-step reflux-precipitation polymerization 377:422 In this study, the polymeric hydrophilic ionic liquid-modified magnetic (Fe3O4@MPS@PMAC) nanoparticles were synthesized via a one-step reflux-precipitation polymerization. 28765562 3 51 theme MPS 650:652 arg1 nanoparticles 659:671 the synthesized Fe3O4@MPS@PMAC nanoparticles 628:671 the synthesized Fe3O4@MPS@PMAC nanoparticles 628:671 Owing to the excellent hydrophilicity and strong electrostatic interaction toward glycopeptides of the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride (MAC), the synthesized Fe3O4@MPS@PMAC nanoparticles exhibited outstanding performance in glycopeptide enrichment with high detection sensitivity (10 fmol), large binding capacity (100 μg mg-1) and satisfied enrichment recovery (approximately 82%). 28765562 5 52 theme glycopeptides 1018:1030 arg1 total 1004:1008 A total 1002:1008 A total of 1274 glycopeptides from 536 glycoproteins 1002:1053 A total of 1274 glycopeptides from 536 glycoproteins were identified in three replicate analyses of 50 μg of HeLa exosome proteins. 28765562 3 53 theme electrostatic 474:486 arg1 interaction 488:498 strong electrostatic interaction 467:498 strong electrostatic interaction 467:498 Owing to the excellent hydrophilicity and strong electrostatic interaction toward glycopeptides of the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride (MAC), the synthesized Fe3O4@MPS@PMAC nanoparticles exhibited outstanding performance in glycopeptide enrichment with high detection sensitivity (10 fmol), large binding capacity (100 μg mg-1) and satisfied enrichment recovery (approximately 82%). 28765562 0 54 theme magnetic 51:58 arg1 nanoparticles 60:72 magnetic nanoparticles 51:72 magnetic nanoparticles for the highly selective enrichment of N-linked glycopeptides 51:134 Polymeric hydrophilic ionic liquids used to modify magnetic nanoparticles for the highly selective enrichment of N-linked glycopeptides. 28765562 4 55 theme @ 907:907 arg1 nanoparticles 917:929 the newly developed Fe3O4@MPS@PMAC nanoparticles 882:929 the newly developed Fe3O4@MPS@PMAC nanoparticles 882:929 Furthermore, the newly developed Fe3O4@MPS@PMAC nanoparticles were applied for the glycopeptide enrichment of HeLa exosome proteins. 28765562 3 56 theme @ 653:653 arg1 nanoparticles 659:671 the synthesized Fe3O4@MPS@PMAC nanoparticles 628:671 the synthesized Fe3O4@MPS@PMAC nanoparticles 628:671 Owing to the excellent hydrophilicity and strong electrostatic interaction toward glycopeptides of the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride (MAC), the synthesized Fe3O4@MPS@PMAC nanoparticles exhibited outstanding performance in glycopeptide enrichment with high detection sensitivity (10 fmol), large binding capacity (100 μg mg-1) and satisfied enrichment recovery (approximately 82%). 28765562 3 57 theme detection 744:752 arg1 sensitivity 754:764 high detection sensitivity 739:764 high detection sensitivity (10 fmol) 739:774 Owing to the excellent hydrophilicity and strong electrostatic interaction toward glycopeptides of the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride (MAC), the synthesized Fe3O4@MPS@PMAC nanoparticles exhibited outstanding performance in glycopeptide enrichment with high detection sensitivity (10 fmol), large binding capacity (100 μg mg-1) and satisfied enrichment recovery (approximately 82%). 28765562 3 57 theme detection 744:752 arg1 fmol 770:773 10 fmol 767:773 10 fmol 767:773 Owing to the excellent hydrophilicity and strong electrostatic interaction toward glycopeptides of the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride (MAC), the synthesized Fe3O4@MPS@PMAC nanoparticles exhibited outstanding performance in glycopeptide enrichment with high detection sensitivity (10 fmol), large binding capacity (100 μg mg-1) and satisfied enrichment recovery (approximately 82%). 28765562 0 58 gly glycopeptides 122:134 arg2 glycopeptides 122:134 N-linked glycopeptides 113:134 N-linked glycopeptides 113:134 Polymeric hydrophilic ionic liquids used to modify magnetic nanoparticles for the highly selective enrichment of N-linked glycopeptides. 28765562 3 59 theme binding 783:789 arg1 capacity 791:798 large binding capacity 777:798 large binding capacity (100 μg mg-1) 777:812 Owing to the excellent hydrophilicity and strong electrostatic interaction toward glycopeptides of the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride (MAC), the synthesized Fe3O4@MPS@PMAC nanoparticles exhibited outstanding performance in glycopeptide enrichment with high detection sensitivity (10 fmol), large binding capacity (100 μg mg-1) and satisfied enrichment recovery (approximately 82%). 28765562 3 59 theme binding 783:789 arg1 100 μg mg-1 801:811 100 μg mg-1 801:811 100 μg mg-1 801:811 Owing to the excellent hydrophilicity and strong electrostatic interaction toward glycopeptides of the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride (MAC), the synthesized Fe3O4@MPS@PMAC nanoparticles exhibited outstanding performance in glycopeptide enrichment with high detection sensitivity (10 fmol), large binding capacity (100 μg mg-1) and satisfied enrichment recovery (approximately 82%). 28765562 4 60 theme Fe3O4 902:906 arg1 nanoparticles 917:929 the newly developed Fe3O4@MPS@PMAC nanoparticles 882:929 the newly developed Fe3O4@MPS@PMAC nanoparticles 882:929 Furthermore, the newly developed Fe3O4@MPS@PMAC nanoparticles were applied for the glycopeptide enrichment of HeLa exosome proteins. 28765562 5 61 theme 536 1037:1039 arg1 glycoproteins 1041:1053 536 glycoproteins 1037:1053 536 glycoproteins 1037:1053 A total of 1274 glycopeptides from 536 glycoproteins were identified in three replicate analyses of 50 μg of HeLa exosome proteins. 28765562 2 62 theme @ 335:335 arg1 magnetic 316:323 magnetic 316:323 magnetic 316:323 In this study, the polymeric hydrophilic ionic liquid-modified magnetic (Fe3O4@MPS@PMAC) nanoparticles were synthesized via a one-step reflux-precipitation polymerization. 28765562 2 62 theme @ 335:335 arg1 PMAC 336:339 Fe3O4@MPS@PMAC 326:339 Fe3O4@MPS@PMAC 326:339 In this study, the polymeric hydrophilic ionic liquid-modified magnetic (Fe3O4@MPS@PMAC) nanoparticles were synthesized via a one-step reflux-precipitation polymerization. 28765562 6 63 theme glycoproteomic 1215:1228 arg1 analysis 1230:1237 glycoproteomic analysis 1215:1237 glycoproteomic analysis 1215:1237 These results demonstrate the potential of Fe3O4@MPS@PMAC nanoparticles for both glycoproteomic analysis and exosome research. 28765562 3 64 gly glycopeptide 710:721 arg2 glycopeptide 710:721 glycopeptide enrichment 710:732 glycopeptide enrichment with high detection sensitivity (10 fmol), large binding capacity (100 μg mg-1) and satisfied enrichment recovery (approximately 82%) 710:866 Owing to the excellent hydrophilicity and strong electrostatic interaction toward glycopeptides of the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride (MAC), the synthesized Fe3O4@MPS@PMAC nanoparticles exhibited outstanding performance in glycopeptide enrichment with high detection sensitivity (10 fmol), large binding capacity (100 μg mg-1) and satisfied enrichment recovery (approximately 82%). 28765562 4 65 theme @ 911:911 arg1 nanoparticles 917:929 the newly developed Fe3O4@MPS@PMAC nanoparticles 882:929 the newly developed Fe3O4@MPS@PMAC nanoparticles 882:929 Furthermore, the newly developed Fe3O4@MPS@PMAC nanoparticles were applied for the glycopeptide enrichment of HeLa exosome proteins. 28765562 3 66 theme Fe3O4 644:648 arg1 nanoparticles 659:671 the synthesized Fe3O4@MPS@PMAC nanoparticles 628:671 the synthesized Fe3O4@MPS@PMAC nanoparticles 628:671 Owing to the excellent hydrophilicity and strong electrostatic interaction toward glycopeptides of the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride (MAC), the synthesized Fe3O4@MPS@PMAC nanoparticles exhibited outstanding performance in glycopeptide enrichment with high detection sensitivity (10 fmol), large binding capacity (100 μg mg-1) and satisfied enrichment recovery (approximately 82%). 28765562 2 67 theme MPS 332:334 arg1 magnetic 316:323 magnetic 316:323 magnetic 316:323 In this study, the polymeric hydrophilic ionic liquid-modified magnetic (Fe3O4@MPS@PMAC) nanoparticles were synthesized via a one-step reflux-precipitation polymerization. 28765562 2 67 theme MPS 332:334 arg1 PMAC 336:339 Fe3O4@MPS@PMAC 326:339 Fe3O4@MPS@PMAC 326:339 In this study, the polymeric hydrophilic ionic liquid-modified magnetic (Fe3O4@MPS@PMAC) nanoparticles were synthesized via a one-step reflux-precipitation polymerization. 28765562 3 68 theme ethyl 587:591 arg1 MAC 622:624 MAC 622:624 MAC 622:624 Owing to the excellent hydrophilicity and strong electrostatic interaction toward glycopeptides of the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride (MAC), the synthesized Fe3O4@MPS@PMAC nanoparticles exhibited outstanding performance in glycopeptide enrichment with high detection sensitivity (10 fmol), large binding capacity (100 μg mg-1) and satisfied enrichment recovery (approximately 82%). 28765562 3 68 theme ethyl 587:591 arg1 chloride 612:619 the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride 524:619 chloride 612:619 Owing to the excellent hydrophilicity and strong electrostatic interaction toward glycopeptides of the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride (MAC), the synthesized Fe3O4@MPS@PMAC nanoparticles exhibited outstanding performance in glycopeptide enrichment with high detection sensitivity (10 fmol), large binding capacity (100 μg mg-1) and satisfied enrichment recovery (approximately 82%). 28765562 3 69 theme satisfied 818:826 arg1 % 865:865 approximately 82% 849:865 approximately 82% 849:865 Owing to the excellent hydrophilicity and strong electrostatic interaction toward glycopeptides of the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride (MAC), the synthesized Fe3O4@MPS@PMAC nanoparticles exhibited outstanding performance in glycopeptide enrichment with high detection sensitivity (10 fmol), large binding capacity (100 μg mg-1) and satisfied enrichment recovery (approximately 82%). 28765562 3 69 theme satisfied 818:826 arg1 recovery 839:846 satisfied enrichment recovery 818:846 satisfied enrichment recovery (approximately 82%) 818:866 Owing to the excellent hydrophilicity and strong electrostatic interaction toward glycopeptides of the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride (MAC), the synthesized Fe3O4@MPS@PMAC nanoparticles exhibited outstanding performance in glycopeptide enrichment with high detection sensitivity (10 fmol), large binding capacity (100 μg mg-1) and satisfied enrichment recovery (approximately 82%). 28765562 1 70 gly glycopeptides 158:170 arg2 glycopeptides 158:170 glycopeptides 158:170 glycopeptides 158:170 The low abundance of glycopeptides in biological samples makes it necessary to enrich them before further analysis. 28765562 3 71 theme @ 649:649 arg1 nanoparticles 659:671 the synthesized Fe3O4@MPS@PMAC nanoparticles 628:671 the synthesized Fe3O4@MPS@PMAC nanoparticles 628:671 Owing to the excellent hydrophilicity and strong electrostatic interaction toward glycopeptides of the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride (MAC), the synthesized Fe3O4@MPS@PMAC nanoparticles exhibited outstanding performance in glycopeptide enrichment with high detection sensitivity (10 fmol), large binding capacity (100 μg mg-1) and satisfied enrichment recovery (approximately 82%). 28765562 0 72 link N-linked 113:120 arg1 glycopeptides 122:134 N-linked glycopeptides 113:134 N-linked glycopeptides 113:134 Polymeric hydrophilic ionic liquids used to modify magnetic nanoparticles for the highly selective enrichment of N-linked glycopeptides. 28765562 1 73 theme low 141:143 arg1 abundance 145:153 The low abundance 137:153 The low abundance of glycopeptides in biological samples 137:192 The low abundance of glycopeptides in biological samples makes it necessary to enrich them before further analysis. 28765562 1 74 theme further 235:241 arg1 analysis 243:250 further analysis 235:250 further analysis 235:250 The low abundance of glycopeptides in biological samples makes it necessary to enrich them before further analysis. 28765562 4 75 theme HeLa 979:982 arg1 proteins 992:999 HeLa exosome proteins 979:999 HeLa exosome proteins 979:999 Furthermore, the newly developed Fe3O4@MPS@PMAC nanoparticles were applied for the glycopeptide enrichment of HeLa exosome proteins. 28765562 3 76 theme outstanding 683:693 arg1 performance 695:705 outstanding performance 683:705 outstanding performance in glycopeptide enrichment with high detection sensitivity (10 fmol), large binding capacity (100 μg mg-1) and satisfied enrichment recovery (approximately 82%) 683:866 Owing to the excellent hydrophilicity and strong electrostatic interaction toward glycopeptides of the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride (MAC), the synthesized Fe3O4@MPS@PMAC nanoparticles exhibited outstanding performance in glycopeptide enrichment with high detection sensitivity (10 fmol), large binding capacity (100 μg mg-1) and satisfied enrichment recovery (approximately 82%). 28765562 6 77 theme nanoparticles 1192:1204 arg1 potential 1164:1172 the potential 1160:1172 the potential of Fe3O4@MPS@PMAC nanoparticles for both glycoproteomic analysis and exosome research 1160:1258 These results demonstrate the potential of Fe3O4@MPS@PMAC nanoparticles for both glycoproteomic analysis and exosome research. 28765562 3 78 theme liquid 558:563 arg1 MAC 622:624 MAC 622:624 MAC 622:624 Owing to the excellent hydrophilicity and strong electrostatic interaction toward glycopeptides of the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride (MAC), the synthesized Fe3O4@MPS@PMAC nanoparticles exhibited outstanding performance in glycopeptide enrichment with high detection sensitivity (10 fmol), large binding capacity (100 μg mg-1) and satisfied enrichment recovery (approximately 82%). 28765562 3 78 theme liquid 558:563 arg1 chloride 612:619 the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride 524:619 chloride 612:619 Owing to the excellent hydrophilicity and strong electrostatic interaction toward glycopeptides of the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride (MAC), the synthesized Fe3O4@MPS@PMAC nanoparticles exhibited outstanding performance in glycopeptide enrichment with high detection sensitivity (10 fmol), large binding capacity (100 μg mg-1) and satisfied enrichment recovery (approximately 82%). 28765562 4 79 theme proteins 992:999 arg1 enrichment 965:974 the glycopeptide enrichment 948:974 the glycopeptide enrichment of HeLa exosome proteins 948:999 Furthermore, the newly developed Fe3O4@MPS@PMAC nanoparticles were applied for the glycopeptide enrichment of HeLa exosome proteins. 28765562 3 80 theme synthesized 632:642 arg1 nanoparticles 659:671 the synthesized Fe3O4@MPS@PMAC nanoparticles 628:671 the synthesized Fe3O4@MPS@PMAC nanoparticles 628:671 Owing to the excellent hydrophilicity and strong electrostatic interaction toward glycopeptides of the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride (MAC), the synthesized Fe3O4@MPS@PMAC nanoparticles exhibited outstanding performance in glycopeptide enrichment with high detection sensitivity (10 fmol), large binding capacity (100 μg mg-1) and satisfied enrichment recovery (approximately 82%). 28765562 5 81 theme HeLa 1111:1114 arg1 proteins 1124:1131 HeLa exosome proteins 1111:1131 HeLa exosome proteins 1111:1131 A total of 1274 glycopeptides from 536 glycoproteins were identified in three replicate analyses of 50 μg of HeLa exosome proteins. 28765562 5 82 gly glycopeptides 1018:1030 arg2 glycopeptides 1018:1030 1274 glycopeptides 1013:1030 1274 glycopeptides from 536 glycoproteins 1013:1053 A total of 1274 glycopeptides from 536 glycoproteins were identified in three replicate analyses of 50 μg of HeLa exosome proteins. 28765562 5 82 gly glycopeptides 1018:1030 arg1 glycoproteins 1041:1053 536 glycoproteins 1037:1053 536 glycoproteins 1037:1053 A total of 1274 glycopeptides from 536 glycoproteins were identified in three replicate analyses of 50 μg of HeLa exosome proteins. 28765562 6 83 theme PMAC 1187:1190 arg1 nanoparticles 1192:1204 Fe3O4@MPS@PMAC nanoparticles 1177:1204 Fe3O4@MPS@PMAC nanoparticles 1177:1204 These results demonstrate the potential of Fe3O4@MPS@PMAC nanoparticles for both glycoproteomic analysis and exosome research. 28678517 1 0 gly fucosylation 106:117 arg1 N-glycans 122:130 N-glycans 122:130 N-glycans 122:130 The core fucosylation of N-glycans on glycoproteins is catalyzed by fucosyltransferase 8 (FUT8) in mammalian cells and is involved in various biological functions, such as protein function, cancer progression, and postnatal development. 28678517 1 0 gly fucosylation 106:117 arg1 functions 250:258 various biological functions 231:258 various biological functions 231:258 The core fucosylation of N-glycans on glycoproteins is catalyzed by fucosyltransferase 8 (FUT8) in mammalian cells and is involved in various biological functions, such as protein function, cancer progression, and postnatal development. 28678517 1 0 gly fucosylation 106:117 arg1 glycoproteins 135:147 glycoproteins 135:147 glycoproteins 135:147 The core fucosylation of N-glycans on glycoproteins is catalyzed by fucosyltransferase 8 (FUT8) in mammalian cells and is involved in various biological functions, such as protein function, cancer progression, and postnatal development. 28678517 1 0 gly fucosylation 106:117 arg1 progression 294:304 cancer progression 287:304 cancer progression 287:304 The core fucosylation of N-glycans on glycoproteins is catalyzed by fucosyltransferase 8 (FUT8) in mammalian cells and is involved in various biological functions, such as protein function, cancer progression, and postnatal development. 28678517 1 0 gly fucosylation 106:117 arg1 function 277:284 protein function 269:284 protein function 269:284 The core fucosylation of N-glycans on glycoproteins is catalyzed by fucosyltransferase 8 (FUT8) in mammalian cells and is involved in various biological functions, such as protein function, cancer progression, and postnatal development. 28678517 1 0 gly fucosylation 106:117 arg1 development 321:331 postnatal development 311:331 postnatal development 311:331 The core fucosylation of N-glycans on glycoproteins is catalyzed by fucosyltransferase 8 (FUT8) in mammalian cells and is involved in various biological functions, such as protein function, cancer progression, and postnatal development. 28678517 6 1 theme core 1257:1260 arg1 fucosylation 1262:1273 core fucosylation 1257:1273 core fucosylation 1257:1273 Examining the correlation between the types of N-glycans and the expression levels of FUT8, GnT-IV, and GnT-V in cells revealed that these glycosyltransferases, particularly GnT-IV, play important roles in directing the branching and core fucosylation of N-glycans in vivo. 28678517 1 2 from fucosylation 106:117 arg1 glycoproteins 135:147 glycoproteins 135:147 glycoproteins 135:147 The core fucosylation of N-glycans on glycoproteins is catalyzed by fucosyltransferase 8 (FUT8) in mammalian cells and is involved in various biological functions, such as protein function, cancer progression, and postnatal development. 28678517 1 3 theme protein 269:275 arg1 function 277:284 protein function 269:284 protein function 269:284 The core fucosylation of N-glycans on glycoproteins is catalyzed by fucosyltransferase 8 (FUT8) in mammalian cells and is involved in various biological functions, such as protein function, cancer progression, and postnatal development. 28678517 6 4 theme N-glycans 1278:1286 arg1 branching 1243:1251 branching 1243:1251 branching 1243:1251 Examining the correlation between the types of N-glycans and the expression levels of FUT8, GnT-IV, and GnT-V in cells revealed that these glycosyltransferases, particularly GnT-IV, play important roles in directing the branching and core fucosylation of N-glycans in vivo. 28678517 6 4 theme N-glycans 1278:1286 arg1 fucosylation 1262:1273 core fucosylation 1257:1273 core fucosylation 1257:1273 Examining the correlation between the types of N-glycans and the expression levels of FUT8, GnT-IV, and GnT-V in cells revealed that these glycosyltransferases, particularly GnT-IV, play important roles in directing the branching and core fucosylation of N-glycans in vivo. 28678517 4 5 theme 2,2,6 834:838 arg1 substrate 900:908 a substrate 898:908 a substrate for FUT8 898:917 We found that the tri-antennary glycan [A3(2,4,2) type] terminated with N-acetylglucosamine (GlcNAc), which is generated by N-acetylglucosaminyltransferase (GnT)-IV, is a good substrate for FUT8, but the A3(2,2,6) type of tri-antennary glycan, generated by GnT-V, is not a substrate for FUT8. 28678517 4 5 theme 2,2,6 834:838 arg1 type 841:844 the A3(2,2,6) type 827:844 the A3(2,2,6) type of tri-antennary glycan, generated by GnT-V, 827:889 We found that the tri-antennary glycan [A3(2,4,2) type] terminated with N-acetylglucosamine (GlcNAc), which is generated by N-acetylglucosaminyltransferase (GnT)-IV, is a good substrate for FUT8, but the A3(2,2,6) type of tri-antennary glycan, generated by GnT-V, is not a substrate for FUT8. 28678517 2 6 theme bi-antennary 375:386 arg1 N-glycans 388:396 bi-antennary N-glycans 375:396 bi-antennary N-glycans 375:396 The substrate specificity of FUT8 toward bi-antennary N-glycans has been reported, but it is unclear with regard to tri-antennary and tetra-antennary glycans. 28678517 3 7 theme tri- 561:564 arg1 N-glycans 586:594 tri- and tetra-antennary N-glycans 561:594 tri- and tetra-antennary N-glycans 561:594 Here, we examined the specificity and activity of human FUT8 toward tri- and tetra-antennary N-glycans in the forms of glycopeptides. 28678517 6 8 theme FUT8 1109:1112 arg1 correlation 1037:1047 the correlation 1033:1047 the correlation between the types of N-glycans 1033:1078 Examining the correlation between the types of N-glycans and the expression levels of FUT8, GnT-IV, and GnT-V in cells revealed that these glycosyltransferases, particularly GnT-IV, play important roles in directing the branching and core fucosylation of N-glycans in vivo. 28678517 6 8 theme FUT8 1109:1112 arg1 levels 1099:1104 the expression levels 1084:1104 the expression levels of FUT8 1084:1112 Examining the correlation between the types of N-glycans and the expression levels of FUT8, GnT-IV, and GnT-V in cells revealed that these glycosyltransferases, particularly GnT-IV, play important roles in directing the branching and core fucosylation of N-glycans in vivo. 28678517 7 9 theme N-linked 1383:1390 arg1 glycosylation 1392:1404 N-linked glycosylation 1383:1404 N-linked glycosylation 1383:1404 This study thus provides insights into the interplay among FUT8, GnT-IV, and GnT-V in N-linked glycosylation during the assembly of glycoproteins. 28678517 6 10 theme important 1210:1218 arg1 roles 1220:1224 important roles 1210:1224 important roles 1210:1224 Examining the correlation between the types of N-glycans and the expression levels of FUT8, GnT-IV, and GnT-V in cells revealed that these glycosyltransferases, particularly GnT-IV, play important roles in directing the branching and core fucosylation of N-glycans in vivo. 28678517 6 11 from GnT-IV 1115:1120 arg1 cells 1136:1140 cells 1136:1140 cells 1136:1140 Examining the correlation between the types of N-glycans and the expression levels of FUT8, GnT-IV, and GnT-V in cells revealed that these glycosyltransferases, particularly GnT-IV, play important roles in directing the branching and core fucosylation of N-glycans in vivo. 28678517 1 12 theme cancer 287:292 arg1 progression 294:304 cancer progression 287:304 cancer progression 287:304 The core fucosylation of N-glycans on glycoproteins is catalyzed by fucosyltransferase 8 (FUT8) in mammalian cells and is involved in various biological functions, such as protein function, cancer progression, and postnatal development. 28678517 1 13 gly glycoproteins 135:147 arg1 glycoproteins 135:147 glycoproteins 135:147 glycoproteins 135:147 The core fucosylation of N-glycans on glycoproteins is catalyzed by fucosyltransferase 8 (FUT8) in mammalian cells and is involved in various biological functions, such as protein function, cancer progression, and postnatal development. 28678517 4 14 theme tri-antennary 645:657 arg1 type 677:680 the tri-antennary glycan [A3(2,4,2) type] 641:681 the tri-antennary glycan [A3(2,4,2) type] 641:681 We found that the tri-antennary glycan [A3(2,4,2) type] terminated with N-acetylglucosamine (GlcNAc), which is generated by N-acetylglucosaminyltransferase (GnT)-IV, is a good substrate for FUT8, but the A3(2,2,6) type of tri-antennary glycan, generated by GnT-V, is not a substrate for FUT8. 28678517 4 14 theme tri-antennary 645:657 arg1 substrate 803:811 a good substrate 796:811 a good substrate for FUT8 796:820 We found that the tri-antennary glycan [A3(2,4,2) type] terminated with N-acetylglucosamine (GlcNAc), which is generated by N-acetylglucosaminyltransferase (GnT)-IV, is a good substrate for FUT8, but the A3(2,2,6) type of tri-antennary glycan, generated by GnT-V, is not a substrate for FUT8. 28678517 1 15 theme core 101:104 arg1 fucosylation 106:117 The core fucosylation 97:117 The core fucosylation of N-glycans on glycoproteins 97:147 The core fucosylation of N-glycans on glycoproteins is catalyzed by fucosyltransferase 8 (FUT8) in mammalian cells and is involved in various biological functions, such as protein function, cancer progression, and postnatal development. 28678517 1 16 theme mammalian 196:204 arg1 cells 206:210 mammalian cells 196:210 mammalian cells 196:210 The core fucosylation of N-glycans on glycoproteins is catalyzed by fucosyltransferase 8 (FUT8) in mammalian cells and is involved in various biological functions, such as protein function, cancer progression, and postnatal development. 28678517 6 17 dep branching 1243:1251 arg1 the 1239:1241 the 1239:1241 the 1239:1241 Examining the correlation between the types of N-glycans and the expression levels of FUT8, GnT-IV, and GnT-V in cells revealed that these glycosyltransferases, particularly GnT-IV, play important roles in directing the branching and core fucosylation of N-glycans in vivo. 28678517 3 18 dep specificity 515:525 arg1 the 511:513 the 511:513 the 511:513 Here, we examined the specificity and activity of human FUT8 toward tri- and tetra-antennary N-glycans in the forms of glycopeptides. 28678517 7 19 link N-linked 1383:1390 arg1 glycosylation 1392:1404 N-linked glycosylation 1383:1404 N-linked glycosylation 1383:1404 This study thus provides insights into the interplay among FUT8, GnT-IV, and GnT-V in N-linked glycosylation during the assembly of glycoproteins. 28678517 4 20 theme 2,4,2 670:674 arg1 type 677:680 the tri-antennary glycan [A3(2,4,2) type] 641:681 the tri-antennary glycan [A3(2,4,2) type] 641:681 We found that the tri-antennary glycan [A3(2,4,2) type] terminated with N-acetylglucosamine (GlcNAc), which is generated by N-acetylglucosaminyltransferase (GnT)-IV, is a good substrate for FUT8, but the A3(2,2,6) type of tri-antennary glycan, generated by GnT-V, is not a substrate for FUT8. 28678517 4 20 theme 2,4,2 670:674 arg1 substrate 803:811 a good substrate 796:811 a good substrate for FUT8 796:820 We found that the tri-antennary glycan [A3(2,4,2) type] terminated with N-acetylglucosamine (GlcNAc), which is generated by N-acetylglucosaminyltransferase (GnT)-IV, is a good substrate for FUT8, but the A3(2,2,6) type of tri-antennary glycan, generated by GnT-V, is not a substrate for FUT8. 28678517 2 21 theme tetra-antennary 468:482 arg1 glycans 484:490 tri-antennary and tetra-antennary glycans 450:490 tri-antennary and tetra-antennary glycans 450:490 The substrate specificity of FUT8 toward bi-antennary N-glycans has been reported, but it is unclear with regard to tri-antennary and tetra-antennary glycans. 28678517 1 22 from fucosyltransferase 8 165:184 arg1 cells 206:210 mammalian cells 196:210 mammalian cells 196:210 The core fucosylation of N-glycans on glycoproteins is catalyzed by fucosyltransferase 8 (FUT8) in mammalian cells and is involved in various biological functions, such as protein function, cancer progression, and postnatal development. 28678517 2 23 theme substrate 338:346 arg1 specificity 348:358 The substrate specificity 334:358 The substrate specificity of FUT8 toward bi-antennary N-glycans 334:396 The substrate specificity of FUT8 toward bi-antennary N-glycans has been reported, but it is unclear with regard to tri-antennary and tetra-antennary glycans. 28678517 0 24 theme Substrate 0:8 arg1 Preference 10:19 Substrate Preference 0:19 Substrate Preference 0:19 Substrate Preference and Interplay of Fucosyltransferase 8 and N-Acetylglucosaminyltransferases. 28678517 4 25 theme A3 831:832 arg1 substrate 900:908 a substrate 898:908 a substrate for FUT8 898:917 We found that the tri-antennary glycan [A3(2,4,2) type] terminated with N-acetylglucosamine (GlcNAc), which is generated by N-acetylglucosaminyltransferase (GnT)-IV, is a good substrate for FUT8, but the A3(2,2,6) type of tri-antennary glycan, generated by GnT-V, is not a substrate for FUT8. 28678517 4 25 theme A3 831:832 arg1 type 841:844 the A3(2,2,6) type 827:844 the A3(2,2,6) type of tri-antennary glycan, generated by GnT-V, 827:889 We found that the tri-antennary glycan [A3(2,4,2) type] terminated with N-acetylglucosamine (GlcNAc), which is generated by N-acetylglucosaminyltransferase (GnT)-IV, is a good substrate for FUT8, but the A3(2,2,6) type of tri-antennary glycan, generated by GnT-V, is not a substrate for FUT8. 28678517 1 26 theme N-glycans 122:130 arg1 fucosylation 106:117 The core fucosylation 97:117 The core fucosylation of N-glycans on glycoproteins 97:147 The core fucosylation of N-glycans on glycoproteins is catalyzed by fucosyltransferase 8 (FUT8) in mammalian cells and is involved in various biological functions, such as protein function, cancer progression, and postnatal development. 28678517 2 27 theme tri-antennary 450:462 arg1 glycans 484:490 tri-antennary and tetra-antennary glycans 450:490 tri-antennary and tetra-antennary glycans 450:490 The substrate specificity of FUT8 toward bi-antennary N-glycans has been reported, but it is unclear with regard to tri-antennary and tetra-antennary glycans. 28678517 5 28 theme core 942:945 arg1 fucosylation 947:958 core fucosylation 942:958 core fucosylation 942:958 We also observed that core fucosylation reduced the activity of GnT-IV toward the bi-antennary glycan. 28678517 3 29 theme tetra-antennary 570:584 arg1 N-glycans 586:594 tri- and tetra-antennary N-glycans 561:594 tri- and tetra-antennary N-glycans 561:594 Here, we examined the specificity and activity of human FUT8 toward tri- and tetra-antennary N-glycans in the forms of glycopeptides. 28678517 4 30 theme glycan 659:664 arg1 type 677:680 the tri-antennary glycan [A3(2,4,2) type] 641:681 the tri-antennary glycan [A3(2,4,2) type] 641:681 We found that the tri-antennary glycan [A3(2,4,2) type] terminated with N-acetylglucosamine (GlcNAc), which is generated by N-acetylglucosaminyltransferase (GnT)-IV, is a good substrate for FUT8, but the A3(2,2,6) type of tri-antennary glycan, generated by GnT-V, is not a substrate for FUT8. 28678517 4 30 theme glycan 659:664 arg1 substrate 803:811 a good substrate 796:811 a good substrate for FUT8 796:820 We found that the tri-antennary glycan [A3(2,4,2) type] terminated with N-acetylglucosamine (GlcNAc), which is generated by N-acetylglucosaminyltransferase (GnT)-IV, is a good substrate for FUT8, but the A3(2,2,6) type of tri-antennary glycan, generated by GnT-V, is not a substrate for FUT8. 28678517 3 31 theme FUT8 549:552 arg1 activity 531:538 activity 531:538 activity 531:538 Here, we examined the specificity and activity of human FUT8 toward tri- and tetra-antennary N-glycans in the forms of glycopeptides. 28678517 3 31 theme FUT8 549:552 arg1 specificity 515:525 specificity 515:525 specificity 515:525 Here, we examined the specificity and activity of human FUT8 toward tri- and tetra-antennary N-glycans in the forms of glycopeptides. 28678517 6 32 theme expression 1088:1097 arg1 levels 1099:1104 the expression levels 1084:1104 the expression levels of FUT8 1084:1112 Examining the correlation between the types of N-glycans and the expression levels of FUT8, GnT-IV, and GnT-V in cells revealed that these glycosyltransferases, particularly GnT-IV, play important roles in directing the branching and core fucosylation of N-glycans in vivo. 28678517 3 33 gly glycopeptides 612:624 arg2 glycopeptides 612:624 glycopeptides 612:624 glycopeptides 612:624 Here, we examined the specificity and activity of human FUT8 toward tri- and tetra-antennary N-glycans in the forms of glycopeptides. 28678517 0 34 theme Fucosyltransferase 8 38:57 arg1 Interplay 25:33 Interplay 25:33 Interplay of Fucosyltransferase 8 and N-Acetylglucosaminyltransferases 25:94 Substrate Preference and Interplay of Fucosyltransferase 8 and N-Acetylglucosaminyltransferases. 28678517 0 34 theme Fucosyltransferase 8 38:57 arg1 Preference 10:19 Substrate Preference 0:19 Substrate Preference 0:19 Substrate Preference and Interplay of Fucosyltransferase 8 and N-Acetylglucosaminyltransferases. 28678517 1 35 theme postnatal 311:319 arg1 development 321:331 postnatal development 311:331 postnatal development 311:331 The core fucosylation of N-glycans on glycoproteins is catalyzed by fucosyltransferase 8 (FUT8) in mammalian cells and is involved in various biological functions, such as protein function, cancer progression, and postnatal development. 28678517 6 36 gly fucosylation 1262:1273 arg1 N-glycans 1278:1286 N-glycans 1278:1286 N-glycans 1278:1286 Examining the correlation between the types of N-glycans and the expression levels of FUT8, GnT-IV, and GnT-V in cells revealed that these glycosyltransferases, particularly GnT-IV, play important roles in directing the branching and core fucosylation of N-glycans in vivo. 28678517 3 37 theme glycopeptides 612:624 arg1 forms 603:607 the forms 599:607 the forms of glycopeptides 599:624 Here, we examined the specificity and activity of human FUT8 toward tri- and tetra-antennary N-glycans in the forms of glycopeptides. 28678517 1 38 theme various 231:237 arg1 function 277:284 protein function 269:284 protein function 269:284 The core fucosylation of N-glycans on glycoproteins is catalyzed by fucosyltransferase 8 (FUT8) in mammalian cells and is involved in various biological functions, such as protein function, cancer progression, and postnatal development. 28678517 1 38 theme various 231:237 arg1 functions 250:258 various biological functions 231:258 various biological functions 231:258 The core fucosylation of N-glycans on glycoproteins is catalyzed by fucosyltransferase 8 (FUT8) in mammalian cells and is involved in various biological functions, such as protein function, cancer progression, and postnatal development. 28678517 1 38 theme various 231:237 arg1 progression 294:304 cancer progression 287:304 cancer progression 287:304 The core fucosylation of N-glycans on glycoproteins is catalyzed by fucosyltransferase 8 (FUT8) in mammalian cells and is involved in various biological functions, such as protein function, cancer progression, and postnatal development. 28678517 1 38 theme various 231:237 arg1 development 321:331 postnatal development 311:331 postnatal development 311:331 The core fucosylation of N-glycans on glycoproteins is catalyzed by fucosyltransferase 8 (FUT8) in mammalian cells and is involved in various biological functions, such as protein function, cancer progression, and postnatal development. 28678517 7 39 from interplay 1340:1348 arg1 glycosylation 1392:1404 N-linked glycosylation 1383:1404 N-linked glycosylation 1383:1404 This study thus provides insights into the interplay among FUT8, GnT-IV, and GnT-V in N-linked glycosylation during the assembly of glycoproteins. 28678517 1 40 theme biological 239:248 arg1 function 277:284 protein function 269:284 protein function 269:284 The core fucosylation of N-glycans on glycoproteins is catalyzed by fucosyltransferase 8 (FUT8) in mammalian cells and is involved in various biological functions, such as protein function, cancer progression, and postnatal development. 28678517 1 40 theme biological 239:248 arg1 functions 250:258 various biological functions 231:258 various biological functions 231:258 The core fucosylation of N-glycans on glycoproteins is catalyzed by fucosyltransferase 8 (FUT8) in mammalian cells and is involved in various biological functions, such as protein function, cancer progression, and postnatal development. 28678517 1 40 theme biological 239:248 arg1 progression 294:304 cancer progression 287:304 cancer progression 287:304 The core fucosylation of N-glycans on glycoproteins is catalyzed by fucosyltransferase 8 (FUT8) in mammalian cells and is involved in various biological functions, such as protein function, cancer progression, and postnatal development. 28678517 1 40 theme biological 239:248 arg1 development 321:331 postnatal development 311:331 postnatal development 311:331 The core fucosylation of N-glycans on glycoproteins is catalyzed by fucosyltransferase 8 (FUT8) in mammalian cells and is involved in various biological functions, such as protein function, cancer progression, and postnatal development. 28678517 0 41 theme N-Acetylglucosaminyltransferases 63:94 arg1 Interplay 25:33 Interplay 25:33 Interplay of Fucosyltransferase 8 and N-Acetylglucosaminyltransferases 25:94 Substrate Preference and Interplay of Fucosyltransferase 8 and N-Acetylglucosaminyltransferases. 28678517 0 41 theme N-Acetylglucosaminyltransferases 63:94 arg1 Preference 10:19 Substrate Preference 0:19 Substrate Preference 0:19 Substrate Preference and Interplay of Fucosyltransferase 8 and N-Acetylglucosaminyltransferases. 28678517 4 42 theme glycan 863:868 arg1 substrate 900:908 a substrate 898:908 a substrate for FUT8 898:917 We found that the tri-antennary glycan [A3(2,4,2) type] terminated with N-acetylglucosamine (GlcNAc), which is generated by N-acetylglucosaminyltransferase (GnT)-IV, is a good substrate for FUT8, but the A3(2,2,6) type of tri-antennary glycan, generated by GnT-V, is not a substrate for FUT8. 28678517 4 42 theme glycan 863:868 arg1 type 841:844 the A3(2,2,6) type 827:844 the A3(2,2,6) type of tri-antennary glycan, generated by GnT-V, 827:889 We found that the tri-antennary glycan [A3(2,4,2) type] terminated with N-acetylglucosamine (GlcNAc), which is generated by N-acetylglucosaminyltransferase (GnT)-IV, is a good substrate for FUT8, but the A3(2,2,6) type of tri-antennary glycan, generated by GnT-V, is not a substrate for FUT8. 28678517 4 43 theme tri-antennary 849:861 arg1 glycan 863:868 tri-antennary glycan 849:868 tri-antennary glycan 849:868 We found that the tri-antennary glycan [A3(2,4,2) type] terminated with N-acetylglucosamine (GlcNAc), which is generated by N-acetylglucosaminyltransferase (GnT)-IV, is a good substrate for FUT8, but the A3(2,2,6) type of tri-antennary glycan, generated by GnT-V, is not a substrate for FUT8. 28678517 5 44 theme GnT-IV 984:989 arg1 activity 972:979 the activity 968:979 the activity of GnT-IV toward the bi-antennary glycan 968:1020 We also observed that core fucosylation reduced the activity of GnT-IV toward the bi-antennary glycan. 28678517 2 45 theme FUT8 363:366 arg1 specificity 348:358 The substrate specificity 334:358 The substrate specificity of FUT8 toward bi-antennary N-glycans 334:396 The substrate specificity of FUT8 toward bi-antennary N-glycans has been reported, but it is unclear with regard to tri-antennary and tetra-antennary glycans. 28678517 5 46 theme bi-antennary 1002:1013 arg1 glycan 1015:1020 the bi-antennary glycan 998:1020 the bi-antennary glycan 998:1020 We also observed that core fucosylation reduced the activity of GnT-IV toward the bi-antennary glycan. 28678517 6 47 theme N-glycans 1070:1078 arg1 types 1061:1065 the types 1057:1065 the types of N-glycans 1057:1078 Examining the correlation between the types of N-glycans and the expression levels of FUT8, GnT-IV, and GnT-V in cells revealed that these glycosyltransferases, particularly GnT-IV, play important roles in directing the branching and core fucosylation of N-glycans in vivo. 28678517 4 48 theme N-acetylglucosaminyltransferase 751:781 arg1 -IV 788:790 N-acetylglucosaminyltransferase (GnT)-IV 751:790 N-acetylglucosaminyltransferase (GnT)-IV 751:790 We found that the tri-antennary glycan [A3(2,4,2) type] terminated with N-acetylglucosamine (GlcNAc), which is generated by N-acetylglucosaminyltransferase (GnT)-IV, is a good substrate for FUT8, but the A3(2,2,6) type of tri-antennary glycan, generated by GnT-V, is not a substrate for FUT8. 28678517 7 49 theme glycoproteins 1429:1441 arg1 assembly 1417:1424 the assembly 1413:1424 the assembly of glycoproteins 1413:1441 This study thus provides insights into the interplay among FUT8, GnT-IV, and GnT-V in N-linked glycosylation during the assembly of glycoproteins. 28678517 6 50 from GnT-V 1127:1131 arg1 cells 1136:1140 cells 1136:1140 cells 1136:1140 Examining the correlation between the types of N-glycans and the expression levels of FUT8, GnT-IV, and GnT-V in cells revealed that these glycosyltransferases, particularly GnT-IV, play important roles in directing the branching and core fucosylation of N-glycans in vivo. 28678517 4 51 theme [A3 666:668 arg1 type 677:680 the tri-antennary glycan [A3(2,4,2) type] 641:681 the tri-antennary glycan [A3(2,4,2) type] 641:681 We found that the tri-antennary glycan [A3(2,4,2) type] terminated with N-acetylglucosamine (GlcNAc), which is generated by N-acetylglucosaminyltransferase (GnT)-IV, is a good substrate for FUT8, but the A3(2,2,6) type of tri-antennary glycan, generated by GnT-V, is not a substrate for FUT8. 28678517 4 51 theme [A3 666:668 arg1 substrate 803:811 a good substrate 796:811 a good substrate for FUT8 796:820 We found that the tri-antennary glycan [A3(2,4,2) type] terminated with N-acetylglucosamine (GlcNAc), which is generated by N-acetylglucosaminyltransferase (GnT)-IV, is a good substrate for FUT8, but the A3(2,2,6) type of tri-antennary glycan, generated by GnT-V, is not a substrate for FUT8. 28678517 4 52 theme good 798:801 arg1 type 677:680 the tri-antennary glycan [A3(2,4,2) type] 641:681 the tri-antennary glycan [A3(2,4,2) type] 641:681 We found that the tri-antennary glycan [A3(2,4,2) type] terminated with N-acetylglucosamine (GlcNAc), which is generated by N-acetylglucosaminyltransferase (GnT)-IV, is a good substrate for FUT8, but the A3(2,2,6) type of tri-antennary glycan, generated by GnT-V, is not a substrate for FUT8. 28678517 4 52 theme good 798:801 arg1 substrate 803:811 a good substrate 796:811 a good substrate for FUT8 796:820 We found that the tri-antennary glycan [A3(2,4,2) type] terminated with N-acetylglucosamine (GlcNAc), which is generated by N-acetylglucosaminyltransferase (GnT)-IV, is a good substrate for FUT8, but the A3(2,2,6) type of tri-antennary glycan, generated by GnT-V, is not a substrate for FUT8. 28678517 7 53 gly glycoproteins 1429:1441 arg1 glycoproteins 1429:1441 glycoproteins 1429:1441 glycoproteins 1429:1441 This study thus provides insights into the interplay among FUT8, GnT-IV, and GnT-V in N-linked glycosylation during the assembly of glycoproteins. 28678517 3 54 theme human 543:547 arg1 FUT8 549:552 human FUT8 543:552 human FUT8 543:552 Here, we examined the specificity and activity of human FUT8 toward tri- and tetra-antennary N-glycans in the forms of glycopeptides. 28628526 4 0 theme CD4-independent 924:938 arg1 envelopes 947:955 CD4-dependent (cl2) and CD4-independent (cl20) envelopes 900:955 CD4-dependent (cl2) and CD4-independent (cl20) envelopes concurrently isolated from the cerebral spinal fluid of an SHIV-infected macaque with neurological AIDS and with minimum sequence differences 900:1097 METHODS We characterize, by site-directed mutagenesis, neutralization assay, and structural analysis, a pair of CD4-dependent (cl2) and CD4-independent (cl20) envelopes concurrently isolated from the cerebral spinal fluid of an SHIV-infected macaque with neurological AIDS and with minimum sequence differences. 28628526 7 1 theme gp120 1441:1445 arg1 V1V2 1433:1436 V1V2 1433:1436 V1V2 of gp120 that can destabilize the apex of the envelope spike, with an additional change in V4 that abrogated a potential N-linked glycan to facilitate movement of the V1V2 domain and further expose the coreceptor-binding site 1433:1662 CONCLUSIONS Our data suggested that the determinants of CD4 independence in vivo mapped principally to V1V2 of gp120 that can destabilize the apex of the envelope spike, with an additional change in V4 that abrogated a potential N-linked glycan to facilitate movement of the V1V2 domain and further expose the coreceptor-binding site. 28628526 4 2 theme site-directed 816:828 arg1 mutagenesis 830:840 site-directed mutagenesis 816:840 site-directed mutagenesis 816:840 METHODS We characterize, by site-directed mutagenesis, neutralization assay, and structural analysis, a pair of CD4-dependent (cl2) and CD4-independent (cl20) envelopes concurrently isolated from the cerebral spinal fluid of an SHIV-infected macaque with neurological AIDS and with minimum sequence differences. 28628526 4 3 theme cerebral 988:995 arg1 fluid 1004:1008 the cerebral spinal fluid 984:1008 the cerebral spinal fluid of an SHIV-infected macaque with neurological AIDS and with minimum sequence differences 984:1097 METHODS We characterize, by site-directed mutagenesis, neutralization assay, and structural analysis, a pair of CD4-dependent (cl2) and CD4-independent (cl20) envelopes concurrently isolated from the cerebral spinal fluid of an SHIV-infected macaque with neurological AIDS and with minimum sequence differences. 28628526 4 4 dep CD4-dependent 900:912 arg1 cl2 915:917 cl2 915:917 cl2 915:917 METHODS We characterize, by site-directed mutagenesis, neutralization assay, and structural analysis, a pair of CD4-dependent (cl2) and CD4-independent (cl20) envelopes concurrently isolated from the cerebral spinal fluid of an SHIV-infected macaque with neurological AIDS and with minimum sequence differences. 28628526 4 5 with macaque 1030:1036 arg1 differences 1087:1097 minimum sequence differences 1070:1097 minimum sequence differences 1070:1097 METHODS We characterize, by site-directed mutagenesis, neutralization assay, and structural analysis, a pair of CD4-dependent (cl2) and CD4-independent (cl20) envelopes concurrently isolated from the cerebral spinal fluid of an SHIV-infected macaque with neurological AIDS and with minimum sequence differences. 28628526 4 5 with macaque 1030:1036 arg1 AIDS 1056:1059 neurological AIDS 1043:1059 neurological AIDS 1043:1059 METHODS We characterize, by site-directed mutagenesis, neutralization assay, and structural analysis, a pair of CD4-dependent (cl2) and CD4-independent (cl20) envelopes concurrently isolated from the cerebral spinal fluid of an SHIV-infected macaque with neurological AIDS and with minimum sequence differences. 28628526 6 6 from Mutations 1196:1204 arg1 cl2 1227:1229 cl2 1227:1229 cl2 1227:1229 Mutations of these residues in cl2 increased its CD4 independence in infection, and the effects are cumulative and likely structural. 28628526 3 7 from infection 649:657 arg1 absence 666:672 the absence 662:672 the absence of CD4 662:679 Given that infection of long-lived CD4-low and CD4-negative cells in anatomical compartments such as the brain expands cell tropism in vivo and may serve as potential viral reservoirs that pose challenge for HIV eradication, understanding the evolution to CD4 independence and envelope conformation associated with infection in the absence of CD4 will not only broaden our insights into HIV pathogenesis but may guide functional cure strategies as well. 28628526 4 8 attach isolated 970:977 arg1 fluid 1004:1008 the cerebral spinal fluid 984:1008 the cerebral spinal fluid of an SHIV-infected macaque with neurological AIDS and with minimum sequence differences 984:1097 METHODS We characterize, by site-directed mutagenesis, neutralization assay, and structural analysis, a pair of CD4-dependent (cl2) and CD4-independent (cl20) envelopes concurrently isolated from the cerebral spinal fluid of an SHIV-infected macaque with neurological AIDS and with minimum sequence differences. 28628526 4 8 attach isolated 970:977 arg2 envelopes 947:955 CD4-dependent (cl2) and CD4-independent (cl20) envelopes 900:955 CD4-dependent (cl2) and CD4-independent (cl20) envelopes concurrently isolated from the cerebral spinal fluid of an SHIV-infected macaque with neurological AIDS and with minimum sequence differences 900:1097 METHODS We characterize, by site-directed mutagenesis, neutralization assay, and structural analysis, a pair of CD4-dependent (cl2) and CD4-independent (cl20) envelopes concurrently isolated from the cerebral spinal fluid of an SHIV-infected macaque with neurological AIDS and with minimum sequence differences. 28628526 2 9 theme acid 253:256 arg1 variations 258:267 amino acid variations 247:267 amino acid variations 247:267 This adaptation is through amino acid variations, but the patterns of such variation are not yet well understood. 28628526 7 10 theme coreceptor-binding 1640:1657 arg1 site 1659:1662 the coreceptor-binding site 1636:1662 the coreceptor-binding site 1636:1662 CONCLUSIONS Our data suggested that the determinants of CD4 independence in vivo mapped principally to V1V2 of gp120 that can destabilize the apex of the envelope spike, with an additional change in V4 that abrogated a potential N-linked glycan to facilitate movement of the V1V2 domain and further expose the coreceptor-binding site. 28628526 7 11 theme spike 1493:1497 arg1 apex 1472:1475 the apex 1468:1475 the apex of the envelope spike 1468:1497 CONCLUSIONS Our data suggested that the determinants of CD4 independence in vivo mapped principally to V1V2 of gp120 that can destabilize the apex of the envelope spike, with an additional change in V4 that abrogated a potential N-linked glycan to facilitate movement of the V1V2 domain and further expose the coreceptor-binding site. 28628526 3 12 theme potential 491:499 arg1 reservoirs 507:516 potential viral reservoirs 491:516 potential viral reservoirs that pose challenge for HIV eradication 491:556 Given that infection of long-lived CD4-low and CD4-negative cells in anatomical compartments such as the brain expands cell tropism in vivo and may serve as potential viral reservoirs that pose challenge for HIV eradication, understanding the evolution to CD4 independence and envelope conformation associated with infection in the absence of CD4 will not only broaden our insights into HIV pathogenesis but may guide functional cure strategies as well. 28628526 3 12 theme potential 491:499 arg1 infection 345:353 infection 345:353 infection of long-lived CD4-low and CD4-negative cells in anatomical compartments such as the brain 345:443 Given that infection of long-lived CD4-low and CD4-negative cells in anatomical compartments such as the brain expands cell tropism in vivo and may serve as potential viral reservoirs that pose challenge for HIV eradication, understanding the evolution to CD4 independence and envelope conformation associated with infection in the absence of CD4 will not only broaden our insights into HIV pathogenesis but may guide functional cure strategies as well. 28628526 2 13 theme amino 247:251 arg1 variations 258:267 amino acid variations 247:267 amino acid variations 247:267 This adaptation is through amino acid variations, but the patterns of such variation are not yet well understood. 28628526 4 14 theme sequence 1078:1085 arg1 differences 1087:1097 minimum sequence differences 1070:1097 minimum sequence differences 1070:1097 METHODS We characterize, by site-directed mutagenesis, neutralization assay, and structural analysis, a pair of CD4-dependent (cl2) and CD4-independent (cl20) envelopes concurrently isolated from the cerebral spinal fluid of an SHIV-infected macaque with neurological AIDS and with minimum sequence differences. 28628526 6 15 theme residues 1215:1222 arg1 Mutations 1196:1204 Mutations 1196:1204 Mutations of these residues in cl2 1196:1229 Mutations of these residues in cl2 increased its CD4 independence in infection, and the effects are cumulative and likely structural. 28628526 4 16 theme minimum 1070:1076 arg1 differences 1087:1097 minimum sequence differences 1070:1097 minimum sequence differences 1070:1097 METHODS We characterize, by site-directed mutagenesis, neutralization assay, and structural analysis, a pair of CD4-dependent (cl2) and CD4-independent (cl20) envelopes concurrently isolated from the cerebral spinal fluid of an SHIV-infected macaque with neurological AIDS and with minimum sequence differences. 28628526 3 17 theme cells 394:398 arg1 reservoirs 507:516 potential viral reservoirs 491:516 potential viral reservoirs that pose challenge for HIV eradication 491:556 Given that infection of long-lived CD4-low and CD4-negative cells in anatomical compartments such as the brain expands cell tropism in vivo and may serve as potential viral reservoirs that pose challenge for HIV eradication, understanding the evolution to CD4 independence and envelope conformation associated with infection in the absence of CD4 will not only broaden our insights into HIV pathogenesis but may guide functional cure strategies as well. 28628526 3 17 theme cells 394:398 arg1 infection 345:353 infection 345:353 infection of long-lived CD4-low and CD4-negative cells in anatomical compartments such as the brain 345:443 Given that infection of long-lived CD4-low and CD4-negative cells in anatomical compartments such as the brain expands cell tropism in vivo and may serve as potential viral reservoirs that pose challenge for HIV eradication, understanding the evolution to CD4 independence and envelope conformation associated with infection in the absence of CD4 will not only broaden our insights into HIV pathogenesis but may guide functional cure strategies as well. 28628526 4 18 theme CD4-dependent 900:912 arg1 envelopes 947:955 CD4-dependent (cl2) and CD4-independent (cl20) envelopes 900:955 CD4-dependent (cl2) and CD4-independent (cl20) envelopes concurrently isolated from the cerebral spinal fluid of an SHIV-infected macaque with neurological AIDS and with minimum sequence differences 900:1097 METHODS We characterize, by site-directed mutagenesis, neutralization assay, and structural analysis, a pair of CD4-dependent (cl2) and CD4-independent (cl20) envelopes concurrently isolated from the cerebral spinal fluid of an SHIV-infected macaque with neurological AIDS and with minimum sequence differences. 28628526 0 19 theme Adaptation 44:53 arg1 Determinants 0:11 Determinants 0:11 Determinants of HIV-1 CD4-Independent Brain Adaptation 0:53 Determinants of HIV-1 CD4-Independent Brain Adaptation. 28628526 5 20 theme surrounding 1175:1185 arg1 regions 1187:1193 surrounding regions 1175:1193 surrounding regions 1175:1193 RESULTS Residues different between cl2 and cl20 are mapped to the V1V2 and surrounding regions. 28628526 7 21 theme domain 1610:1615 arg1 movement 1589:1596 movement 1589:1596 movement of the V1V2 domain 1589:1615 CONCLUSIONS Our data suggested that the determinants of CD4 independence in vivo mapped principally to V1V2 of gp120 that can destabilize the apex of the envelope spike, with an additional change in V4 that abrogated a potential N-linked glycan to facilitate movement of the V1V2 domain and further expose the coreceptor-binding site. 28628526 5 22 theme different 1117:1125 arg1 Residues 1108:1115 RESULTS Residues 1100:1115 RESULTS Residues different between cl2 and cl20 1100:1146 RESULTS Residues different between cl2 and cl20 are mapped to the V1V2 and surrounding regions. 28628526 3 23 theme CD4 677:679 arg1 absence 666:672 the absence 662:672 the absence of CD4 662:679 Given that infection of long-lived CD4-low and CD4-negative cells in anatomical compartments such as the brain expands cell tropism in vivo and may serve as potential viral reservoirs that pose challenge for HIV eradication, understanding the evolution to CD4 independence and envelope conformation associated with infection in the absence of CD4 will not only broaden our insights into HIV pathogenesis but may guide functional cure strategies as well. 28628526 4 24 dep METHODS 788:794 arg1 characterize 799:810 characterize 799:810 characterize 799:810 METHODS We characterize, by site-directed mutagenesis, neutralization assay, and structural analysis, a pair of CD4-dependent (cl2) and CD4-independent (cl20) envelopes concurrently isolated from the cerebral spinal fluid of an SHIV-infected macaque with neurological AIDS and with minimum sequence differences. 28628526 6 25 dep cumulative 1296:1305 arg1 cumulative 1296:1305 cumulative 1296:1305 cumulative 1296:1305 Mutations of these residues in cl2 increased its CD4 independence in infection, and the effects are cumulative and likely structural. 28628526 6 25 dep cumulative 1296:1305 arg1 structural 1318:1327 structural 1318:1327 structural 1318:1327 Mutations of these residues in cl2 increased its CD4 independence in infection, and the effects are cumulative and likely structural. 28628526 6 25 dep cumulative 1296:1305 arg1 effects 1284:1290 the effects 1280:1290 the effects 1280:1290 Mutations of these residues in cl2 increased its CD4 independence in infection, and the effects are cumulative and likely structural. 28628526 7 26 from change 1519:1524 arg1 V4 1529:1530 V4 1529:1530 V4 that abrogated a potential N-linked glycan to facilitate movement of the V1V2 domain and further expose the coreceptor-binding site 1529:1662 CONCLUSIONS Our data suggested that the determinants of CD4 independence in vivo mapped principally to V1V2 of gp120 that can destabilize the apex of the envelope spike, with an additional change in V4 that abrogated a potential N-linked glycan to facilitate movement of the V1V2 domain and further expose the coreceptor-binding site. 28628526 7 27 dep CONCLUSIONS 1330:1340 arg1 suggested 1351:1359 suggested 1351:1359 suggested that the determinants of CD4 independence in vivo mapped principally to V1V2 of gp120 that can destabilize the apex of the envelope spike, with an additional change in V4 that abrogated a potential N-linked glycan to facilitate movement of the V1V2 domain and further expose the coreceptor-binding site. 1351:1663 CONCLUSIONS Our data suggested that the determinants of CD4 independence in vivo mapped principally to V1V2 of gp120 that can destabilize the apex of the envelope spike, with an additional change in V4 that abrogated a potential N-linked glycan to facilitate movement of the V1V2 domain and further expose the coreceptor-binding site. 28628526 1 28 from environment 104:114 arg1 usage 123:127 its usage 119:127 its usage of receptors 119:140 BACKGROUND HIV-1 is known to adapt to the local environment in its usage of receptors, and it can become CD4 independent in the brain where the receptor is scarce. 28628526 3 29 theme CD4-negative 381:392 arg1 cells 394:398 long-lived CD4-low and CD4-negative cells 358:398 long-lived CD4-low and CD4-negative cells 358:398 Given that infection of long-lived CD4-low and CD4-negative cells in anatomical compartments such as the brain expands cell tropism in vivo and may serve as potential viral reservoirs that pose challenge for HIV eradication, understanding the evolution to CD4 independence and envelope conformation associated with infection in the absence of CD4 will not only broaden our insights into HIV pathogenesis but may guide functional cure strategies as well. 28628526 0 30 theme CD4-Independent 22:36 arg1 Adaptation 44:53 HIV-1 CD4-Independent Brain Adaptation 16:53 HIV-1 CD4-Independent Brain Adaptation 16:53 Determinants of HIV-1 CD4-Independent Brain Adaptation. 28628526 3 31 theme viral 501:505 arg1 reservoirs 507:516 potential viral reservoirs 491:516 potential viral reservoirs that pose challenge for HIV eradication 491:556 Given that infection of long-lived CD4-low and CD4-negative cells in anatomical compartments such as the brain expands cell tropism in vivo and may serve as potential viral reservoirs that pose challenge for HIV eradication, understanding the evolution to CD4 independence and envelope conformation associated with infection in the absence of CD4 will not only broaden our insights into HIV pathogenesis but may guide functional cure strategies as well. 28628526 3 31 theme viral 501:505 arg1 infection 345:353 infection 345:353 infection of long-lived CD4-low and CD4-negative cells in anatomical compartments such as the brain 345:443 Given that infection of long-lived CD4-low and CD4-negative cells in anatomical compartments such as the brain expands cell tropism in vivo and may serve as potential viral reservoirs that pose challenge for HIV eradication, understanding the evolution to CD4 independence and envelope conformation associated with infection in the absence of CD4 will not only broaden our insights into HIV pathogenesis but may guide functional cure strategies as well. 28628526 4 32 theme neurological 1043:1054 arg1 AIDS 1056:1059 neurological AIDS 1043:1059 neurological AIDS 1043:1059 METHODS We characterize, by site-directed mutagenesis, neutralization assay, and structural analysis, a pair of CD4-dependent (cl2) and CD4-independent (cl20) envelopes concurrently isolated from the cerebral spinal fluid of an SHIV-infected macaque with neurological AIDS and with minimum sequence differences. 28628526 0 33 theme HIV-1 16:20 arg1 Adaptation 44:53 HIV-1 CD4-Independent Brain Adaptation 16:53 HIV-1 CD4-Independent Brain Adaptation 16:53 Determinants of HIV-1 CD4-Independent Brain Adaptation. 28628526 7 34 theme N-linked 1559:1566 arg1 glycan 1568:1573 a potential N-linked glycan 1547:1573 a potential N-linked glycan to facilitate movement of the V1V2 domain and further expose the coreceptor-binding site 1547:1662 CONCLUSIONS Our data suggested that the determinants of CD4 independence in vivo mapped principally to V1V2 of gp120 that can destabilize the apex of the envelope spike, with an additional change in V4 that abrogated a potential N-linked glycan to facilitate movement of the V1V2 domain and further expose the coreceptor-binding site. 28628526 4 35 theme structural 869:878 arg1 analysis 880:887 structural analysis 869:887 structural analysis 869:887 METHODS We characterize, by site-directed mutagenesis, neutralization assay, and structural analysis, a pair of CD4-dependent (cl2) and CD4-independent (cl20) envelopes concurrently isolated from the cerebral spinal fluid of an SHIV-infected macaque with neurological AIDS and with minimum sequence differences. 28628526 1 36 theme local 98:102 arg1 environment 104:114 the local environment 94:114 the local environment in its usage of receptors 94:140 BACKGROUND HIV-1 is known to adapt to the local environment in its usage of receptors, and it can become CD4 independent in the brain where the receptor is scarce. 28628526 3 37 theme long-lived 358:367 arg1 cells 394:398 long-lived CD4-low and CD4-negative cells 358:398 long-lived CD4-low and CD4-negative cells 358:398 Given that infection of long-lived CD4-low and CD4-negative cells in anatomical compartments such as the brain expands cell tropism in vivo and may serve as potential viral reservoirs that pose challenge for HIV eradication, understanding the evolution to CD4 independence and envelope conformation associated with infection in the absence of CD4 will not only broaden our insights into HIV pathogenesis but may guide functional cure strategies as well. 28628526 3 38 theme cell 453:456 arg1 tropism 458:464 cell tropism 453:464 cell tropism 453:464 Given that infection of long-lived CD4-low and CD4-negative cells in anatomical compartments such as the brain expands cell tropism in vivo and may serve as potential viral reservoirs that pose challenge for HIV eradication, understanding the evolution to CD4 independence and envelope conformation associated with infection in the absence of CD4 will not only broaden our insights into HIV pathogenesis but may guide functional cure strategies as well. 28628526 7 39 theme envelope 1484:1491 arg1 spike 1493:1497 the envelope spike 1480:1497 the envelope spike 1480:1497 CONCLUSIONS Our data suggested that the determinants of CD4 independence in vivo mapped principally to V1V2 of gp120 that can destabilize the apex of the envelope spike, with an additional change in V4 that abrogated a potential N-linked glycan to facilitate movement of the V1V2 domain and further expose the coreceptor-binding site. 28628526 3 40 theme HIV 542:544 arg1 eradication 546:556 HIV eradication 542:556 HIV eradication 542:556 Given that infection of long-lived CD4-low and CD4-negative cells in anatomical compartments such as the brain expands cell tropism in vivo and may serve as potential viral reservoirs that pose challenge for HIV eradication, understanding the evolution to CD4 independence and envelope conformation associated with infection in the absence of CD4 will not only broaden our insights into HIV pathogenesis but may guide functional cure strategies as well. 28628526 3 41 theme anatomical 403:412 arg1 compartments 414:425 anatomical compartments 403:425 anatomical compartments such as the brain 403:443 Given that infection of long-lived CD4-low and CD4-negative cells in anatomical compartments such as the brain expands cell tropism in vivo and may serve as potential viral reservoirs that pose challenge for HIV eradication, understanding the evolution to CD4 independence and envelope conformation associated with infection in the absence of CD4 will not only broaden our insights into HIV pathogenesis but may guide functional cure strategies as well. 28628526 3 41 theme anatomical 403:412 arg1 brain 439:443 the brain 435:443 the brain 435:443 Given that infection of long-lived CD4-low and CD4-negative cells in anatomical compartments such as the brain expands cell tropism in vivo and may serve as potential viral reservoirs that pose challenge for HIV eradication, understanding the evolution to CD4 independence and envelope conformation associated with infection in the absence of CD4 will not only broaden our insights into HIV pathogenesis but may guide functional cure strategies as well. 28628526 0 42 theme Brain 38:42 arg1 Adaptation 44:53 HIV-1 CD4-Independent Brain Adaptation 16:53 HIV-1 CD4-Independent Brain Adaptation 16:53 Determinants of HIV-1 CD4-Independent Brain Adaptation. 28628526 5 43 theme RESULTS 1100:1106 arg1 Residues 1108:1115 RESULTS Residues 1100:1115 RESULTS Residues different between cl2 and cl20 1100:1146 RESULTS Residues different between cl2 and cl20 are mapped to the V1V2 and surrounding regions. 28628526 3 44 theme CD4-low 369:375 arg1 cells 394:398 long-lived CD4-low and CD4-negative cells 358:398 long-lived CD4-low and CD4-negative cells 358:398 Given that infection of long-lived CD4-low and CD4-negative cells in anatomical compartments such as the brain expands cell tropism in vivo and may serve as potential viral reservoirs that pose challenge for HIV eradication, understanding the evolution to CD4 independence and envelope conformation associated with infection in the absence of CD4 will not only broaden our insights into HIV pathogenesis but may guide functional cure strategies as well. 28628526 4 45 theme envelopes 947:955 arg1 pair 892:895 a pair 890:895 a pair of CD4-dependent (cl2) and CD4-independent (cl20) envelopes concurrently isolated from the cerebral spinal fluid of an SHIV-infected macaque with neurological AIDS and with minimum sequence differences 890:1097 METHODS We characterize, by site-directed mutagenesis, neutralization assay, and structural analysis, a pair of CD4-dependent (cl2) and CD4-independent (cl20) envelopes concurrently isolated from the cerebral spinal fluid of an SHIV-infected macaque with neurological AIDS and with minimum sequence differences. 28628526 7 46 theme potential 1549:1557 arg1 glycan 1568:1573 a potential N-linked glycan 1547:1573 a potential N-linked glycan to facilitate movement of the V1V2 domain and further expose the coreceptor-binding site 1547:1662 CONCLUSIONS Our data suggested that the determinants of CD4 independence in vivo mapped principally to V1V2 of gp120 that can destabilize the apex of the envelope spike, with an additional change in V4 that abrogated a potential N-linked glycan to facilitate movement of the V1V2 domain and further expose the coreceptor-binding site. 28628526 4 47 dep CD4-independent 924:938 arg1 cl20 941:944 cl20 941:944 cl20 941:944 METHODS We characterize, by site-directed mutagenesis, neutralization assay, and structural analysis, a pair of CD4-dependent (cl2) and CD4-independent (cl20) envelopes concurrently isolated from the cerebral spinal fluid of an SHIV-infected macaque with neurological AIDS and with minimum sequence differences. 28628526 3 48 theme CD4 590:592 arg1 independence 594:605 CD4 independence 590:605 CD4 independence 590:605 Given that infection of long-lived CD4-low and CD4-negative cells in anatomical compartments such as the brain expands cell tropism in vivo and may serve as potential viral reservoirs that pose challenge for HIV eradication, understanding the evolution to CD4 independence and envelope conformation associated with infection in the absence of CD4 will not only broaden our insights into HIV pathogenesis but may guide functional cure strategies as well. 28628526 2 49 theme variation 295:303 arg1 patterns 278:285 the patterns 274:285 the patterns of such variation 274:303 This adaptation is through amino acid variations, but the patterns of such variation are not yet well understood. 28628526 3 50 dep will 681:684 arg1 expands 445:451 expands 445:451 expands 445:451 Given that infection of long-lived CD4-low and CD4-negative cells in anatomical compartments such as the brain expands cell tropism in vivo and may serve as potential viral reservoirs that pose challenge for HIV eradication, understanding the evolution to CD4 independence and envelope conformation associated with infection in the absence of CD4 will not only broaden our insights into HIV pathogenesis but may guide functional cure strategies as well. 28628526 3 50 dep will 681:684 arg1 only 690:693 only 690:693 only 690:693 Given that infection of long-lived CD4-low and CD4-negative cells in anatomical compartments such as the brain expands cell tropism in vivo and may serve as potential viral reservoirs that pose challenge for HIV eradication, understanding the evolution to CD4 independence and envelope conformation associated with infection in the absence of CD4 will not only broaden our insights into HIV pathogenesis but may guide functional cure strategies as well. 28628526 3 50 dep will 681:684 arg1 serve 482:486 serve 482:486 may serve as potential viral reservoirs that pose challenge for HIV eradication 478:556 Given that infection of long-lived CD4-low and CD4-negative cells in anatomical compartments such as the brain expands cell tropism in vivo and may serve as potential viral reservoirs that pose challenge for HIV eradication, understanding the evolution to CD4 independence and envelope conformation associated with infection in the absence of CD4 will not only broaden our insights into HIV pathogenesis but may guide functional cure strategies as well. 28628526 4 51 theme neutralization 843:856 arg1 assay 858:862 neutralization assay 843:862 neutralization assay 843:862 METHODS We characterize, by site-directed mutagenesis, neutralization assay, and structural analysis, a pair of CD4-dependent (cl2) and CD4-independent (cl20) envelopes concurrently isolated from the cerebral spinal fluid of an SHIV-infected macaque with neurological AIDS and with minimum sequence differences. 28628526 2 52 theme such 290:293 arg1 variation 295:303 such variation 290:303 such variation 290:303 This adaptation is through amino acid variations, but the patterns of such variation are not yet well understood. 28628526 3 53 theme HIV 721:723 arg1 pathogenesis 725:736 HIV pathogenesis 721:736 HIV pathogenesis 721:736 Given that infection of long-lived CD4-low and CD4-negative cells in anatomical compartments such as the brain expands cell tropism in vivo and may serve as potential viral reservoirs that pose challenge for HIV eradication, understanding the evolution to CD4 independence and envelope conformation associated with infection in the absence of CD4 will not only broaden our insights into HIV pathogenesis but may guide functional cure strategies as well. 28628526 5 54 dep V1V2 1166:1169 arg1 the 1162:1164 the 1162:1164 the 1162:1164 RESULTS Residues different between cl2 and cl20 are mapped to the V1V2 and surrounding regions. 28628526 3 55 theme functional 752:761 arg1 strategies 768:777 functional cure strategies 752:777 functional cure strategies 752:777 Given that infection of long-lived CD4-low and CD4-negative cells in anatomical compartments such as the brain expands cell tropism in vivo and may serve as potential viral reservoirs that pose challenge for HIV eradication, understanding the evolution to CD4 independence and envelope conformation associated with infection in the absence of CD4 will not only broaden our insights into HIV pathogenesis but may guide functional cure strategies as well. 28628526 6 56 theme CD4 1245:1247 arg1 independence 1249:1260 its CD4 independence 1241:1260 its CD4 independence 1241:1260 Mutations of these residues in cl2 increased its CD4 independence in infection, and the effects are cumulative and likely structural. 28628526 3 57 theme envelope 611:618 arg1 conformation 620:631 envelope conformation 611:631 envelope conformation 611:631 Given that infection of long-lived CD4-low and CD4-negative cells in anatomical compartments such as the brain expands cell tropism in vivo and may serve as potential viral reservoirs that pose challenge for HIV eradication, understanding the evolution to CD4 independence and envelope conformation associated with infection in the absence of CD4 will not only broaden our insights into HIV pathogenesis but may guide functional cure strategies as well. 28628526 7 58 theme CD4 1386:1388 arg1 independence 1390:1401 CD4 independence 1386:1401 CD4 independence 1386:1401 CONCLUSIONS Our data suggested that the determinants of CD4 independence in vivo mapped principally to V1V2 of gp120 that can destabilize the apex of the envelope spike, with an additional change in V4 that abrogated a potential N-linked glycan to facilitate movement of the V1V2 domain and further expose the coreceptor-binding site. 28628526 7 59 link N-linked 1559:1566 arg1 glycan 1568:1573 a potential N-linked glycan 1547:1573 a potential N-linked glycan to facilitate movement of the V1V2 domain and further expose the coreceptor-binding site 1547:1662 CONCLUSIONS Our data suggested that the determinants of CD4 independence in vivo mapped principally to V1V2 of gp120 that can destabilize the apex of the envelope spike, with an additional change in V4 that abrogated a potential N-linked glycan to facilitate movement of the V1V2 domain and further expose the coreceptor-binding site. 28628526 7 60 theme V1V2 1605:1608 arg1 domain 1610:1615 the V1V2 domain 1601:1615 the V1V2 domain 1601:1615 CONCLUSIONS Our data suggested that the determinants of CD4 independence in vivo mapped principally to V1V2 of gp120 that can destabilize the apex of the envelope spike, with an additional change in V4 that abrogated a potential N-linked glycan to facilitate movement of the V1V2 domain and further expose the coreceptor-binding site. 28628526 3 61 theme cure 763:766 arg1 strategies 768:777 functional cure strategies 752:777 functional cure strategies 752:777 Given that infection of long-lived CD4-low and CD4-negative cells in anatomical compartments such as the brain expands cell tropism in vivo and may serve as potential viral reservoirs that pose challenge for HIV eradication, understanding the evolution to CD4 independence and envelope conformation associated with infection in the absence of CD4 will not only broaden our insights into HIV pathogenesis but may guide functional cure strategies as well. 28628526 7 62 theme independence 1390:1401 arg1 determinants 1370:1381 the determinants 1366:1381 the determinants of CD4 independence 1366:1401 CONCLUSIONS Our data suggested that the determinants of CD4 independence in vivo mapped principally to V1V2 of gp120 that can destabilize the apex of the envelope spike, with an additional change in V4 that abrogated a potential N-linked glycan to facilitate movement of the V1V2 domain and further expose the coreceptor-binding site. 28628526 4 63 theme macaque 1030:1036 arg1 fluid 1004:1008 the cerebral spinal fluid 984:1008 the cerebral spinal fluid of an SHIV-infected macaque with neurological AIDS and with minimum sequence differences 984:1097 METHODS We characterize, by site-directed mutagenesis, neutralization assay, and structural analysis, a pair of CD4-dependent (cl2) and CD4-independent (cl20) envelopes concurrently isolated from the cerebral spinal fluid of an SHIV-infected macaque with neurological AIDS and with minimum sequence differences. 28628526 7 64 theme additional 1508:1517 arg1 change 1519:1524 an additional change 1505:1524 an additional change in V4 that abrogated a potential N-linked glycan to facilitate movement of the V1V2 domain and further expose the coreceptor-binding site 1505:1662 CONCLUSIONS Our data suggested that the determinants of CD4 independence in vivo mapped principally to V1V2 of gp120 that can destabilize the apex of the envelope spike, with an additional change in V4 that abrogated a potential N-linked glycan to facilitate movement of the V1V2 domain and further expose the coreceptor-binding site. 28628526 3 65 from infection 345:353 arg1 compartments 414:425 anatomical compartments 403:425 anatomical compartments such as the brain 403:443 Given that infection of long-lived CD4-low and CD4-negative cells in anatomical compartments such as the brain expands cell tropism in vivo and may serve as potential viral reservoirs that pose challenge for HIV eradication, understanding the evolution to CD4 independence and envelope conformation associated with infection in the absence of CD4 will not only broaden our insights into HIV pathogenesis but may guide functional cure strategies as well. 28628526 3 65 from infection 345:353 arg1 brain 439:443 the brain 435:443 the brain 435:443 Given that infection of long-lived CD4-low and CD4-negative cells in anatomical compartments such as the brain expands cell tropism in vivo and may serve as potential viral reservoirs that pose challenge for HIV eradication, understanding the evolution to CD4 independence and envelope conformation associated with infection in the absence of CD4 will not only broaden our insights into HIV pathogenesis but may guide functional cure strategies as well. 28628526 1 66 theme BACKGROUND 56:65 arg1 HIV-1 67:71 BACKGROUND HIV-1 56:71 BACKGROUND HIV-1 56:71 BACKGROUND HIV-1 is known to adapt to the local environment in its usage of receptors, and it can become CD4 independent in the brain where the receptor is scarce. 28628526 1 67 theme receptors 132:140 arg1 usage 123:127 its usage 119:127 its usage of receptors 119:140 BACKGROUND HIV-1 is known to adapt to the local environment in its usage of receptors, and it can become CD4 independent in the brain where the receptor is scarce. 28628526 4 68 theme spinal 997:1002 arg1 fluid 1004:1008 the cerebral spinal fluid 984:1008 the cerebral spinal fluid of an SHIV-infected macaque with neurological AIDS and with minimum sequence differences 984:1097 METHODS We characterize, by site-directed mutagenesis, neutralization assay, and structural analysis, a pair of CD4-dependent (cl2) and CD4-independent (cl20) envelopes concurrently isolated from the cerebral spinal fluid of an SHIV-infected macaque with neurological AIDS and with minimum sequence differences. 28187141 0 0 theme GH 77:78 arg1 xylanase 83:90 a thermophilic GH 10 xylanase 62:90 a thermophilic GH 10 xylanase from Aspergillus fumigatus 62:117 Role of N-linked glycosylation in the enzymatic properties of a thermophilic GH 10 xylanase from Aspergillus fumigatus expressed in Pichia pastoris. 28187141 3 1 gly N-glycosylated 500:513 arg1 Af-XYNA 515:521 The N-glycosylated Af-XYNA 496:521 The N-glycosylated Af-XYNA (WT) 496:526 The N-glycosylated Af-XYNA (WT) exhibited favorable temperature and pH optima (75°C and pH 5.0) and good thermostability (maintaining stable at 60°C). 28187141 3 1 gly N-glycosylated 500:513 arg1 WT 524:525 WT 524:525 WT 524:525 The N-glycosylated Af-XYNA (WT) exhibited favorable temperature and pH optima (75°C and pH 5.0) and good thermostability (maintaining stable at 60°C). 28187141 3 2 dep thermostability 601:615 arg1 maintaining 618:628 maintaining 618:628 maintaining stable at 60°C 618:643 The N-glycosylated Af-XYNA (WT) exhibited favorable temperature and pH optima (75°C and pH 5.0) and good thermostability (maintaining stable at 60°C). 28187141 0 3 theme thermophilic 64:75 arg1 xylanase 83:90 a thermophilic GH 10 xylanase 62:90 a thermophilic GH 10 xylanase from Aspergillus fumigatus 62:117 Role of N-linked glycosylation in the enzymatic properties of a thermophilic GH 10 xylanase from Aspergillus fumigatus expressed in Pichia pastoris. 28187141 3 4 theme at 637:638 arg1 60°C 640:643 stable at 60°C 630:643 stable at 60°C 630:643 The N-glycosylated Af-XYNA (WT) exhibited favorable temperature and pH optima (75°C and pH 5.0) and good thermostability (maintaining stable at 60°C). 28187141 2 5 theme hydrolase 327:335 arg1 family 342:347 glycoside hydrolase (GH) family 10 317:350 glycoside hydrolase (GH) family 10 317:350 In this study, a xylanase (Af-XYNA) of glycoside hydrolase (GH) family 10 from Aspergillus fumigatus harboring three potential N-glycosylation sites (N87, N124 and N335) was heterologously produced in Pichia pastoris. 28187141 7 6 theme thermal 1243:1249 arg1 stability 1251:1259 thermal stability 1243:1259 thermal stability 1243:1259 This study demonstrated that the effects of glycosylation at different degrees and sites were diverse, in which the glycan linked to N124 played a key role in pH and thermal stability of Af-XYNA. 28187141 0 7 theme xylanase 83:90 arg1 properties 48:57 the enzymatic properties 34:57 the enzymatic properties of a thermophilic GH 10 xylanase from Aspergillus fumigatus 34:117 Role of N-linked glycosylation in the enzymatic properties of a thermophilic GH 10 xylanase from Aspergillus fumigatus expressed in Pichia pastoris. 28187141 0 8 from Role 0:3 arg1 properties 48:57 the enzymatic properties 34:57 the enzymatic properties of a thermophilic GH 10 xylanase from Aspergillus fumigatus 34:117 Role of N-linked glycosylation in the enzymatic properties of a thermophilic GH 10 xylanase from Aspergillus fumigatus expressed in Pichia pastoris. 28187141 0 9 link N-linked 8:15 arg1 glycosylation 17:29 N-linked glycosylation 8:29 N-linked glycosylation 8:29 Role of N-linked glycosylation in the enzymatic properties of a thermophilic GH 10 xylanase from Aspergillus fumigatus expressed in Pichia pastoris. 28187141 1 10 theme enzyme 260:265 arg1 functions 267:275 enzyme functions 260:275 enzyme functions 260:275 N-Glycosylation is a posttranslational modification commonly occurred in fungi and plays roles in a variety of enzyme functions. 28187141 0 11 from properties 48:57 arg1 fumigatus 109:117 Aspergillus fumigatus 97:117 Aspergillus fumigatus 97:117 Role of N-linked glycosylation in the enzymatic properties of a thermophilic GH 10 xylanase from Aspergillus fumigatus expressed in Pichia pastoris. 28187141 6 12 theme higher 1024:1029 arg1 degree 1047:1052 higher N-glycosylation degree 1024:1052 higher N-glycosylation degree 1024:1052 Further thermodynamic analysis revealed that the enzyme with higher N-glycosylation degree was more thermostable. 28187141 1 13 theme functions 267:275 arg1 variety 249:255 a variety 247:255 a variety of enzyme functions 247:275 N-Glycosylation is a posttranslational modification commonly occurred in fungi and plays roles in a variety of enzyme functions. 28187141 1 13 theme functions 267:275 arg1 functions 267:275 enzyme functions 260:275 enzyme functions 260:275 N-Glycosylation is a posttranslational modification commonly occurred in fungi and plays roles in a variety of enzyme functions. 28187141 2 14 theme Pichia 479:484 arg1 pastoris 486:493 Pichia pastoris 479:493 Pichia pastoris 479:493 In this study, a xylanase (Af-XYNA) of glycoside hydrolase (GH) family 10 from Aspergillus fumigatus harboring three potential N-glycosylation sites (N87, N124 and N335) was heterologously produced in Pichia pastoris. 28187141 2 15 dep sites 421:425 arg1 N87 428:430 N87 428:430 N87 428:430 In this study, a xylanase (Af-XYNA) of glycoside hydrolase (GH) family 10 from Aspergillus fumigatus harboring three potential N-glycosylation sites (N87, N124 and N335) was heterologously produced in Pichia pastoris. 28187141 5 16 theme lower 902:906 arg1 activity 917:924 lower specific activity 902:924 lower specific activity 902:924 The deglycosylated DE and mutant N124T showed narrower pH adaptation range, lower specific activity, and worse pH and thermal stability. 28187141 3 17 dep temperature 548:558 arg1 75°C 575:578 75°C 575:578 75°C 575:578 The N-glycosylated Af-XYNA (WT) exhibited favorable temperature and pH optima (75°C and pH 5.0) and good thermostability (maintaining stable at 60°C). 28187141 3 17 dep temperature 548:558 arg1 pH 584:585 pH 5.0 584:589 pH 5.0 584:589 The N-glycosylated Af-XYNA (WT) exhibited favorable temperature and pH optima (75°C and pH 5.0) and good thermostability (maintaining stable at 60°C). 28187141 7 18 theme different 1138:1146 arg1 degrees 1148:1154 different degrees 1138:1154 different degrees 1138:1154 This study demonstrated that the effects of glycosylation at different degrees and sites were diverse, in which the glycan linked to N124 played a key role in pH and thermal stability of Af-XYNA. 28187141 5 19 theme deglycosylated 830:843 arg1 DE 845:846 The deglycosylated DE 826:846 The deglycosylated DE 826:846 The deglycosylated DE and mutant N124T showed narrower pH adaptation range, lower specific activity, and worse pH and thermal stability. 28187141 3 20 theme N-glycosylated 500:513 arg1 Af-XYNA 515:521 The N-glycosylated Af-XYNA 496:521 The N-glycosylated Af-XYNA (WT) 496:526 The N-glycosylated Af-XYNA (WT) exhibited favorable temperature and pH optima (75°C and pH 5.0) and good thermostability (maintaining stable at 60°C). 28187141 3 20 theme N-glycosylated 500:513 arg1 WT 524:525 WT 524:525 WT 524:525 The N-glycosylated Af-XYNA (WT) exhibited favorable temperature and pH optima (75°C and pH 5.0) and good thermostability (maintaining stable at 60°C). 28187141 1 21 theme posttranslational 170:186 arg1 modification 188:199 a posttranslational modification 168:199 a posttranslational modification commonly occurred in fungi 168:226 N-Glycosylation is a posttranslational modification commonly occurred in fungi and plays roles in a variety of enzyme functions. 28187141 1 21 theme posttranslational 170:186 arg1 N-Glycosylation 149:163 N-Glycosylation 149:163 N-Glycosylation 149:163 N-Glycosylation is a posttranslational modification commonly occurred in fungi and plays roles in a variety of enzyme functions. 28187141 7 22 attach linked 1200:1205 arg1 N124 1210:1213 N124 1210:1213 N124 1210:1213 This study demonstrated that the effects of glycosylation at different degrees and sites were diverse, in which the glycan linked to N124 played a key role in pH and thermal stability of Af-XYNA. 28187141 7 22 attach linked 1200:1205 arg2 glycan 1193:1198 the glycan 1189:1198 the glycan linked to N124 1189:1213 This study demonstrated that the effects of glycosylation at different degrees and sites were diverse, in which the glycan linked to N124 played a key role in pH and thermal stability of Af-XYNA. 28187141 4 23 theme N-glycosylation 669:683 arg1 role 661:664 the role 657:664 the role of N-glycosylation on Af-XYNA 657:694 To reveal the role of N-glycosylation on Af-XYNA, the enzyme was deglycosylated by endo-β-N-acetylglucosaminidase H (DE) or modified by site-directed mutagenesis at N124 (N124T). 28187141 4 24 from N124 812:815 arg1 mutagenesis 797:807 site-directed mutagenesis 783:807 site-directed mutagenesis at N124 (N124T) 783:823 To reveal the role of N-glycosylation on Af-XYNA, the enzyme was deglycosylated by endo-β-N-acetylglucosaminidase H (DE) or modified by site-directed mutagenesis at N124 (N124T). 28187141 4 25 theme site-directed 783:795 arg1 mutagenesis 797:807 site-directed mutagenesis 783:807 site-directed mutagenesis at N124 (N124T) 783:823 To reveal the role of N-glycosylation on Af-XYNA, the enzyme was deglycosylated by endo-β-N-acetylglucosaminidase H (DE) or modified by site-directed mutagenesis at N124 (N124T). 28187141 3 26 theme favorable 538:546 arg1 temperature 548:558 favorable temperature and pH optima 538:572 temperature 548:558 The N-glycosylated Af-XYNA (WT) exhibited favorable temperature and pH optima (75°C and pH 5.0) and good thermostability (maintaining stable at 60°C). 28187141 2 27 theme family 342:347 arg1 Af-XYNA 305:311 Af-XYNA 305:311 Af-XYNA 305:311 In this study, a xylanase (Af-XYNA) of glycoside hydrolase (GH) family 10 from Aspergillus fumigatus harboring three potential N-glycosylation sites (N87, N124 and N335) was heterologously produced in Pichia pastoris. 28187141 2 27 theme family 342:347 arg1 xylanase 295:302 a xylanase 293:302 a xylanase (Af-XYNA) of glycoside hydrolase (GH) family 10 from Aspergillus fumigatus harboring three potential N-glycosylation sites (N87, N124 and N335) 293:446 In this study, a xylanase (Af-XYNA) of glycoside hydrolase (GH) family 10 from Aspergillus fumigatus harboring three potential N-glycosylation sites (N87, N124 and N335) was heterologously produced in Pichia pastoris. 28187141 0 28 theme glycosylation 17:29 arg1 Role 0:3 Role 0:3 Role of N-linked glycosylation in the enzymatic properties of a thermophilic GH 10 xylanase from Aspergillus fumigatus 0:117 Role of N-linked glycosylation in the enzymatic properties of a thermophilic GH 10 xylanase from Aspergillus fumigatus expressed in Pichia pastoris. 28187141 7 29 theme Af-XYNA 1264:1270 arg1 pH 1236:1237 pH 1236:1237 pH 1236:1237 This study demonstrated that the effects of glycosylation at different degrees and sites were diverse, in which the glycan linked to N124 played a key role in pH and thermal stability of Af-XYNA. 28187141 7 29 theme Af-XYNA 1264:1270 arg1 stability 1251:1259 thermal stability 1243:1259 thermal stability 1243:1259 This study demonstrated that the effects of glycosylation at different degrees and sites were diverse, in which the glycan linked to N124 played a key role in pH and thermal stability of Af-XYNA. 28187141 5 30 theme pH 881:882 arg1 range 895:899 narrower pH adaptation range 872:899 narrower pH adaptation range 872:899 The deglycosylated DE and mutant N124T showed narrower pH adaptation range, lower specific activity, and worse pH and thermal stability. 28187141 2 31 theme potential 395:403 arg1 sites 421:425 three potential N-glycosylation sites 389:425 three potential N-glycosylation sites (N87, N124 and N335) 389:446 In this study, a xylanase (Af-XYNA) of glycoside hydrolase (GH) family 10 from Aspergillus fumigatus harboring three potential N-glycosylation sites (N87, N124 and N335) was heterologously produced in Pichia pastoris. 28187141 0 32 theme N-linked 8:15 arg1 glycosylation 17:29 N-linked glycosylation 8:29 N-linked glycosylation 8:29 Role of N-linked glycosylation in the enzymatic properties of a thermophilic GH 10 xylanase from Aspergillus fumigatus expressed in Pichia pastoris. 28187141 5 33 theme narrower 872:879 arg1 range 895:899 narrower pH adaptation range 872:899 narrower pH adaptation range 872:899 The deglycosylated DE and mutant N124T showed narrower pH adaptation range, lower specific activity, and worse pH and thermal stability. 28187141 5 34 theme adaptation 884:893 arg1 range 895:899 narrower pH adaptation range 872:899 narrower pH adaptation range 872:899 The deglycosylated DE and mutant N124T showed narrower pH adaptation range, lower specific activity, and worse pH and thermal stability. 28187141 6 35 theme thermodynamic 971:983 arg1 analysis 985:992 Further thermodynamic analysis 963:992 Further thermodynamic analysis 963:992 Further thermodynamic analysis revealed that the enzyme with higher N-glycosylation degree was more thermostable. 28187141 4 36 gly deglycosylated 712:725 arg1 enzyme 701:706 the enzyme 697:706 the enzyme 697:706 To reveal the role of N-glycosylation on Af-XYNA, the enzyme was deglycosylated by endo-β-N-acetylglucosaminidase H (DE) or modified by site-directed mutagenesis at N124 (N124T). 28187141 5 37 theme worse 931:935 arg1 pH 937:938 worse pH 931:938 worse pH 931:938 The deglycosylated DE and mutant N124T showed narrower pH adaptation range, lower specific activity, and worse pH and thermal stability. 28187141 0 38 theme Pichia 132:137 arg1 pastoris 139:146 Pichia pastoris 132:146 Pichia pastoris 132:146 Role of N-linked glycosylation in the enzymatic properties of a thermophilic GH 10 xylanase from Aspergillus fumigatus expressed in Pichia pastoris. 28187141 3 39 theme good 596:599 arg1 thermostability 601:615 good thermostability 596:615 good thermostability (maintaining stable at 60°C) 596:644 The N-glycosylated Af-XYNA (WT) exhibited favorable temperature and pH optima (75°C and pH 5.0) and good thermostability (maintaining stable at 60°C). 28187141 3 40 theme pH 564:565 arg1 optima 567:572 favorable temperature and pH optima 538:572 optima 567:572 The N-glycosylated Af-XYNA (WT) exhibited favorable temperature and pH optima (75°C and pH 5.0) and good thermostability (maintaining stable at 60°C). 28187141 6 41 theme Further 963:969 arg1 analysis 985:992 Further thermodynamic analysis 963:992 Further thermodynamic analysis 963:992 Further thermodynamic analysis revealed that the enzyme with higher N-glycosylation degree was more thermostable. 28187141 3 42 from 60°C 640:643 arg1 at 637:638 stable at 60°C 630:643 stable at 60°C 630:643 The N-glycosylated Af-XYNA (WT) exhibited favorable temperature and pH optima (75°C and pH 5.0) and good thermostability (maintaining stable at 60°C). 28187141 6 43 with enzyme 1012:1017 arg1 degree 1047:1052 higher N-glycosylation degree 1024:1052 higher N-glycosylation degree 1024:1052 Further thermodynamic analysis revealed that the enzyme with higher N-glycosylation degree was more thermostable. 28187141 7 44 theme key 1224:1226 arg1 role 1228:1231 a key role 1222:1231 a key role 1222:1231 This study demonstrated that the effects of glycosylation at different degrees and sites were diverse, in which the glycan linked to N124 played a key role in pH and thermal stability of Af-XYNA. 28187141 5 45 theme thermal 944:950 arg1 stability 952:960 thermal stability 944:960 thermal stability 944:960 The deglycosylated DE and mutant N124T showed narrower pH adaptation range, lower specific activity, and worse pH and thermal stability. 28187141 2 46 theme glycoside 317:325 arg1 family 342:347 glycoside hydrolase (GH) family 10 317:350 glycoside hydrolase (GH) family 10 317:350 In this study, a xylanase (Af-XYNA) of glycoside hydrolase (GH) family 10 from Aspergillus fumigatus harboring three potential N-glycosylation sites (N87, N124 and N335) was heterologously produced in Pichia pastoris. 28187141 0 47 theme enzymatic 38:46 arg1 properties 48:57 the enzymatic properties 34:57 the enzymatic properties of a thermophilic GH 10 xylanase from Aspergillus fumigatus 34:117 Role of N-linked glycosylation in the enzymatic properties of a thermophilic GH 10 xylanase from Aspergillus fumigatus expressed in Pichia pastoris. 28187141 7 48 from sites 1160:1164 arg1 effects 1110:1116 the effects 1106:1116 the effects of glycosylation at different degrees and sites 1106:1164 This study demonstrated that the effects of glycosylation at different degrees and sites were diverse, in which the glycan linked to N124 played a key role in pH and thermal stability of Af-XYNA. 28187141 7 48 from sites 1160:1164 arg1 diverse 1171:1177 diverse 1171:1177 diverse 1171:1177 This study demonstrated that the effects of glycosylation at different degrees and sites were diverse, in which the glycan linked to N124 played a key role in pH and thermal stability of Af-XYNA. 28187141 0 49 gly glycosylation 17:29 arg1 xylanase 83:90 a thermophilic GH 10 xylanase 62:90 a thermophilic GH 10 xylanase from Aspergillus fumigatus 62:117 Role of N-linked glycosylation in the enzymatic properties of a thermophilic GH 10 xylanase from Aspergillus fumigatus expressed in Pichia pastoris. 28187141 7 50 from degrees 1148:1154 arg1 effects 1110:1116 the effects 1106:1116 the effects of glycosylation at different degrees and sites 1106:1164 This study demonstrated that the effects of glycosylation at different degrees and sites were diverse, in which the glycan linked to N124 played a key role in pH and thermal stability of Af-XYNA. 28187141 7 50 from degrees 1148:1154 arg1 diverse 1171:1177 diverse 1171:1177 diverse 1171:1177 This study demonstrated that the effects of glycosylation at different degrees and sites were diverse, in which the glycan linked to N124 played a key role in pH and thermal stability of Af-XYNA. 28187141 4 51 from role 661:664 arg1 Af-XYNA 688:694 Af-XYNA 688:694 Af-XYNA 688:694 To reveal the role of N-glycosylation on Af-XYNA, the enzyme was deglycosylated by endo-β-N-acetylglucosaminidase H (DE) or modified by site-directed mutagenesis at N124 (N124T). 28187141 4 52 theme endo-β-N-acetylglucosaminidase 730:759 arg1 DE 764:765 DE 764:765 DE 764:765 To reveal the role of N-glycosylation on Af-XYNA, the enzyme was deglycosylated by endo-β-N-acetylglucosaminidase H (DE) or modified by site-directed mutagenesis at N124 (N124T). 28187141 4 52 theme endo-β-N-acetylglucosaminidase 730:759 arg1 H 761:761 endo-β-N-acetylglucosaminidase H 730:761 endo-β-N-acetylglucosaminidase H (DE) 730:766 To reveal the role of N-glycosylation on Af-XYNA, the enzyme was deglycosylated by endo-β-N-acetylglucosaminidase H (DE) or modified by site-directed mutagenesis at N124 (N124T). 28187141 5 53 gly deglycosylated 830:843 arg1 DE 845:846 The deglycosylated DE 826:846 The deglycosylated DE 826:846 The deglycosylated DE and mutant N124T showed narrower pH adaptation range, lower specific activity, and worse pH and thermal stability. 28187141 3 54 theme stable 630:635 arg1 60°C 640:643 stable at 60°C 630:643 stable at 60°C 630:643 The N-glycosylated Af-XYNA (WT) exhibited favorable temperature and pH optima (75°C and pH 5.0) and good thermostability (maintaining stable at 60°C). 28187141 5 55 theme mutant 852:857 arg1 N124T 859:863 mutant N124T 852:863 mutant N124T 852:863 The deglycosylated DE and mutant N124T showed narrower pH adaptation range, lower specific activity, and worse pH and thermal stability. 28187141 5 56 theme specific 908:915 arg1 activity 917:924 lower specific activity 902:924 lower specific activity 902:924 The deglycosylated DE and mutant N124T showed narrower pH adaptation range, lower specific activity, and worse pH and thermal stability. 28187141 6 57 theme N-glycosylation 1031:1045 arg1 degree 1047:1052 higher N-glycosylation degree 1024:1052 higher N-glycosylation degree 1024:1052 Further thermodynamic analysis revealed that the enzyme with higher N-glycosylation degree was more thermostable. 28187141 2 58 gly N-glycosylation 405:419 arg2 three 389:393 three 389:393 three 389:393 In this study, a xylanase (Af-XYNA) of glycoside hydrolase (GH) family 10 from Aspergillus fumigatus harboring three potential N-glycosylation sites (N87, N124 and N335) was heterologously produced in Pichia pastoris. 28187141 2 58 gly N-glycosylation 405:419 arg2 sites 421:425 three potential N-glycosylation sites 389:425 three potential N-glycosylation sites (N87, N124 and N335) 389:446 In this study, a xylanase (Af-XYNA) of glycoside hydrolase (GH) family 10 from Aspergillus fumigatus harboring three potential N-glycosylation sites (N87, N124 and N335) was heterologously produced in Pichia pastoris. 28187141 2 59 from fumigatus 369:377 arg1 Af-XYNA 305:311 Af-XYNA 305:311 Af-XYNA 305:311 In this study, a xylanase (Af-XYNA) of glycoside hydrolase (GH) family 10 from Aspergillus fumigatus harboring three potential N-glycosylation sites (N87, N124 and N335) was heterologously produced in Pichia pastoris. 28187141 2 59 from fumigatus 369:377 arg1 xylanase 295:302 a xylanase 293:302 a xylanase (Af-XYNA) of glycoside hydrolase (GH) family 10 from Aspergillus fumigatus harboring three potential N-glycosylation sites (N87, N124 and N335) 293:446 In this study, a xylanase (Af-XYNA) of glycoside hydrolase (GH) family 10 from Aspergillus fumigatus harboring three potential N-glycosylation sites (N87, N124 and N335) was heterologously produced in Pichia pastoris. 28187141 2 60 theme N-glycosylation 405:419 arg1 sites 421:425 three potential N-glycosylation sites 389:425 three potential N-glycosylation sites (N87, N124 and N335) 389:446 In this study, a xylanase (Af-XYNA) of glycoside hydrolase (GH) family 10 from Aspergillus fumigatus harboring three potential N-glycosylation sites (N87, N124 and N335) was heterologously produced in Pichia pastoris. 28187141 2 61 theme GH 338:339 arg1 family 342:347 glycoside hydrolase (GH) family 10 317:350 glycoside hydrolase (GH) family 10 317:350 In this study, a xylanase (Af-XYNA) of glycoside hydrolase (GH) family 10 from Aspergillus fumigatus harboring three potential N-glycosylation sites (N87, N124 and N335) was heterologously produced in Pichia pastoris. 28187141 7 62 theme glycosylation 1121:1133 arg1 effects 1110:1116 the effects 1106:1116 the effects of glycosylation at different degrees and sites 1106:1164 This study demonstrated that the effects of glycosylation at different degrees and sites were diverse, in which the glycan linked to N124 played a key role in pH and thermal stability of Af-XYNA. 28187141 7 62 theme glycosylation 1121:1133 arg1 diverse 1171:1177 diverse 1171:1177 diverse 1171:1177 This study demonstrated that the effects of glycosylation at different degrees and sites were diverse, in which the glycan linked to N124 played a key role in pH and thermal stability of Af-XYNA. 28187141 0 63 from fumigatus 109:117 arg1 xylanase 83:90 a thermophilic GH 10 xylanase 62:90 a thermophilic GH 10 xylanase from Aspergillus fumigatus 62:117 Role of N-linked glycosylation in the enzymatic properties of a thermophilic GH 10 xylanase from Aspergillus fumigatus expressed in Pichia pastoris. 28187141 0 63 from fumigatus 109:117 arg1 properties 48:57 the enzymatic properties 34:57 the enzymatic properties of a thermophilic GH 10 xylanase from Aspergillus fumigatus 34:117 Role of N-linked glycosylation in the enzymatic properties of a thermophilic GH 10 xylanase from Aspergillus fumigatus expressed in Pichia pastoris. 26864433 6 0 theme complexes 1296:1304 arg1 role 1242:1245 in vivo role 1234:1245 in vivo role 1234:1245 Analysis of protein glycosylation in the STT3A, STT3B and MagT1/TUSC3 null cell lines revealed that these cell lines are superior tools for investigating the in vivo role and substrate preferences of the STT3A and STT3B complexes. 26864433 6 0 theme complexes 1296:1304 arg1 preferences 1261:1271 substrate preferences 1251:1271 substrate preferences 1251:1271 Analysis of protein glycosylation in the STT3A, STT3B and MagT1/TUSC3 null cell lines revealed that these cell lines are superior tools for investigating the in vivo role and substrate preferences of the STT3A and STT3B complexes. 26864433 3 1 theme OST 600:602 arg1 complexes 604:612 the two OST complexes 592:612 the two OST complexes 592:612 siRNA mediated knockdowns of STT3A and STT3B in HeLa cells have shown that the two OST complexes have partially non-overlapping roles in N-linked glycosylation. 26864433 6 2 dep in 1234:1235 arg1 vivo 1237:1240 vivo 1237:1240 vivo 1237:1240 Analysis of protein glycosylation in the STT3A, STT3B and MagT1/TUSC3 null cell lines revealed that these cell lines are superior tools for investigating the in vivo role and substrate preferences of the STT3A and STT3B complexes. 26864433 5 3 theme CRISPR/Cas9 869:879 arg1 technology 894:903 the CRISPR/Cas9 gene editing technology 865:903 the CRISPR/Cas9 gene editing technology 865:903 Here, we have used the CRISPR/Cas9 gene editing technology to create viable HEK293 derived cells lines that are deficient for a single catalytic subunit (STT3A or STT3B) or two STT3B-specific accessory subunits (MagT1 and TUSC3). 26864433 5 4 theme derived 929:935 arg1 lines 943:947 viable HEK293 derived cells lines 915:947 viable HEK293 derived cells lines that are deficient for a single catalytic subunit (STT3A or STT3B) or two STT3B-specific accessory subunits (MagT1 and TUSC3) 915:1073 Here, we have used the CRISPR/Cas9 gene editing technology to create viable HEK293 derived cells lines that are deficient for a single catalytic subunit (STT3A or STT3B) or two STT3B-specific accessory subunits (MagT1 and TUSC3). 26864433 6 5 from glycosylation 1096:1108 arg1 lines 1156:1160 the STT3A, STT3B and MagT1/TUSC3 null cell lines 1113:1160 the STT3A, STT3B and MagT1/TUSC3 null cell lines 1113:1160 Analysis of protein glycosylation in the STT3A, STT3B and MagT1/TUSC3 null cell lines revealed that these cell lines are superior tools for investigating the in vivo role and substrate preferences of the STT3A and STT3B complexes. 26864433 3 6 theme non-overlapping 629:643 arg1 roles 645:649 partially non-overlapping roles 619:649 partially non-overlapping roles 619:649 siRNA mediated knockdowns of STT3A and STT3B in HeLa cells have shown that the two OST complexes have partially non-overlapping roles in N-linked glycosylation. 26864433 1 7 theme modification 248:259 arg1 glycosylation 198:210 Asparagine linked glycosylation 180:210 Asparagine linked glycosylation of proteins 180:222 Asparagine linked glycosylation of proteins is an essential protein modification reaction in most eukaryotic organisms. 26864433 1 7 theme modification 248:259 arg1 reaction 261:268 an essential protein modification reaction 227:268 an essential protein modification reaction in most eukaryotic organisms 227:297 Asparagine linked glycosylation of proteins is an essential protein modification reaction in most eukaryotic organisms. 26864433 6 8 theme cell 1182:1185 arg1 lines 1187:1191 these cell lines 1176:1191 these cell lines 1176:1191 Analysis of protein glycosylation in the STT3A, STT3B and MagT1/TUSC3 null cell lines revealed that these cell lines are superior tools for investigating the in vivo role and substrate preferences of the STT3A and STT3B complexes. 26864433 6 8 theme cell 1182:1185 arg1 tools 1206:1210 superior tools 1197:1210 superior tools for investigating the in vivo role and substrate preferences of the STT3A and STT3B complexes 1197:1304 Analysis of protein glycosylation in the STT3A, STT3B and MagT1/TUSC3 null cell lines revealed that these cell lines are superior tools for investigating the in vivo role and substrate preferences of the STT3A and STT3B complexes. 26864433 4 9 theme mediated 704:711 arg1 depletion 713:721 incomplete siRNA mediated depletion 687:721 incomplete siRNA mediated depletion of STT3A or STT3B 687:739 However, incomplete siRNA mediated depletion of STT3A or STT3B reduces the impact of OST complex loss, thereby complicating the interpretation of experimental results. 26864433 2 10 theme Metazoan 300:307 arg1 organisms 309:317 Metazoan organisms 300:317 Metazoan organisms 300:317 Metazoan organisms express two oligosaccharyltransferase complexes that are composed of a catalytic subunit (STT3A or STT3B) assembled with a shared set of accessory subunits and one to two complex specific subunits. 26864433 5 11 theme viable 915:920 arg1 HEK293 922:927 viable HEK293 915:927 viable HEK293 derived cells lines that are deficient for a single catalytic subunit (STT3A or STT3B) or two STT3B-specific accessory subunits (MagT1 and TUSC3) 915:1073 Here, we have used the CRISPR/Cas9 gene editing technology to create viable HEK293 derived cells lines that are deficient for a single catalytic subunit (STT3A or STT3B) or two STT3B-specific accessory subunits (MagT1 and TUSC3). 26864433 6 12 theme substrate 1251:1259 arg1 preferences 1261:1271 substrate preferences 1251:1271 substrate preferences 1251:1271 Analysis of protein glycosylation in the STT3A, STT3B and MagT1/TUSC3 null cell lines revealed that these cell lines are superior tools for investigating the in vivo role and substrate preferences of the STT3A and STT3B complexes. 26864433 4 13 theme loss 775:778 arg1 impact 753:758 the impact 749:758 the impact of OST complex loss 749:778 However, incomplete siRNA mediated depletion of STT3A or STT3B reduces the impact of OST complex loss, thereby complicating the interpretation of experimental results. 26864433 1 14 gly glycosylation 198:210 arg1 proteins 215:222 proteins 215:222 proteins 215:222 Asparagine linked glycosylation of proteins is an essential protein modification reaction in most eukaryotic organisms. 26864433 1 15 from reaction 261:268 arg1 organisms 289:297 most eukaryotic organisms 273:297 most eukaryotic organisms 273:297 Asparagine linked glycosylation of proteins is an essential protein modification reaction in most eukaryotic organisms. 26864433 5 16 theme single 974:979 arg1 subunit 991:997 a single catalytic subunit 972:997 a single catalytic subunit (STT3A or STT3B) 972:1014 Here, we have used the CRISPR/Cas9 gene editing technology to create viable HEK293 derived cells lines that are deficient for a single catalytic subunit (STT3A or STT3B) or two STT3B-specific accessory subunits (MagT1 and TUSC3). 26864433 6 17 dep role 1242:1245 arg1 the 1230:1232 the 1230:1232 the 1230:1232 Analysis of protein glycosylation in the STT3A, STT3B and MagT1/TUSC3 null cell lines revealed that these cell lines are superior tools for investigating the in vivo role and substrate preferences of the STT3A and STT3B complexes. 26864433 2 18 theme oligosaccharyltransferase 331:355 arg1 complexes 357:365 two oligosaccharyltransferase complexes 327:365 two oligosaccharyltransferase complexes that are composed of a catalytic subunit (STT3A or STT3B) assembled with a shared set of accessory subunits and one to two complex specific subunits 327:514 Metazoan organisms express two oligosaccharyltransferase complexes that are composed of a catalytic subunit (STT3A or STT3B) assembled with a shared set of accessory subunits and one to two complex specific subunits. 26864433 1 19 theme linked 191:196 arg1 reaction 261:268 an essential protein modification reaction 227:268 an essential protein modification reaction in most eukaryotic organisms 227:297 Asparagine linked glycosylation of proteins is an essential protein modification reaction in most eukaryotic organisms. 26864433 1 19 theme linked 191:196 arg1 glycosylation 198:210 Asparagine linked glycosylation 180:210 Asparagine linked glycosylation of proteins 180:222 Asparagine linked glycosylation of proteins is an essential protein modification reaction in most eukaryotic organisms. 26864433 0 20 from defects 136:142 arg1 glycosylation 165:177 asparagine linked glycosylation 147:177 asparagine linked glycosylation 147:177 Mammalian cells lacking either the cotranslational or posttranslocational oligosaccharyltransferase complex display substrate-dependent defects in asparagine linked glycosylation. 26864433 6 21 theme in 1234:1235 arg1 role 1242:1245 in vivo role 1234:1245 in vivo role 1234:1245 Analysis of protein glycosylation in the STT3A, STT3B and MagT1/TUSC3 null cell lines revealed that these cell lines are superior tools for investigating the in vivo role and substrate preferences of the STT3A and STT3B complexes. 26864433 0 22 theme oligosaccharyltransferase 74:98 arg1 complex 100:106 either the cotranslational or posttranslocational oligosaccharyltransferase complex 24:106 complex 100:106 Mammalian cells lacking either the cotranslational or posttranslocational oligosaccharyltransferase complex display substrate-dependent defects in asparagine linked glycosylation. 26864433 4 23 theme OST 763:765 arg1 loss 775:778 OST complex loss 763:778 OST complex loss 763:778 However, incomplete siRNA mediated depletion of STT3A or STT3B reduces the impact of OST complex loss, thereby complicating the interpretation of experimental results. 26864433 4 24 theme results 837:843 arg1 interpretation 806:819 the interpretation 802:819 the interpretation of experimental results 802:843 However, incomplete siRNA mediated depletion of STT3A or STT3B reduces the impact of OST complex loss, thereby complicating the interpretation of experimental results. 26864433 2 25 theme subunits 466:473 arg1 subunits 507:514 one to two complex specific subunits 479:514 one to two complex specific subunits 479:514 Metazoan organisms express two oligosaccharyltransferase complexes that are composed of a catalytic subunit (STT3A or STT3B) assembled with a shared set of accessory subunits and one to two complex specific subunits. 26864433 2 25 theme subunits 466:473 arg1 set 449:451 a shared set 440:451 a shared set of accessory subunits and one to two complex specific subunits 440:514 Metazoan organisms express two oligosaccharyltransferase complexes that are composed of a catalytic subunit (STT3A or STT3B) assembled with a shared set of accessory subunits and one to two complex specific subunits. 26864433 2 25 theme subunits 466:473 arg1 subunits 466:473 accessory subunits 456:473 accessory subunits 456:473 Metazoan organisms express two oligosaccharyltransferase complexes that are composed of a catalytic subunit (STT3A or STT3B) assembled with a shared set of accessory subunits and one to two complex specific subunits. 26864433 5 26 theme STT3B-specific 1023:1036 arg1 TUSC3 1068:1072 TUSC3 1068:1072 TUSC3 1068:1072 Here, we have used the CRISPR/Cas9 gene editing technology to create viable HEK293 derived cells lines that are deficient for a single catalytic subunit (STT3A or STT3B) or two STT3B-specific accessory subunits (MagT1 and TUSC3). 26864433 5 26 theme STT3B-specific 1023:1036 arg1 MagT1 1058:1062 MagT1 1058:1062 MagT1 1058:1062 Here, we have used the CRISPR/Cas9 gene editing technology to create viable HEK293 derived cells lines that are deficient for a single catalytic subunit (STT3A or STT3B) or two STT3B-specific accessory subunits (MagT1 and TUSC3). 26864433 5 26 theme STT3B-specific 1023:1036 arg1 subunits 1048:1055 two STT3B-specific accessory subunits 1019:1055 two STT3B-specific accessory subunits (MagT1 and TUSC3) 1019:1073 Here, we have used the CRISPR/Cas9 gene editing technology to create viable HEK293 derived cells lines that are deficient for a single catalytic subunit (STT3A or STT3B) or two STT3B-specific accessory subunits (MagT1 and TUSC3). 26864433 6 27 theme STT3A 1117:1121 arg1 lines 1156:1160 the STT3A, STT3B and MagT1/TUSC3 null cell lines 1113:1160 the STT3A, STT3B and MagT1/TUSC3 null cell lines 1113:1160 Analysis of protein glycosylation in the STT3A, STT3B and MagT1/TUSC3 null cell lines revealed that these cell lines are superior tools for investigating the in vivo role and substrate preferences of the STT3A and STT3B complexes. 26864433 0 28 theme Mammalian 0:8 arg1 cells 10:14 Mammalian cells 0:14 Mammalian cells lacking either the cotranslational or posttranslocational oligosaccharyltransferase complex 0:106 Mammalian cells lacking either the cotranslational or posttranslocational oligosaccharyltransferase complex display substrate-dependent defects in asparagine linked glycosylation. 26864433 5 29 link derived 929:935 arg1 lines 943:947 viable HEK293 derived cells lines 915:947 viable HEK293 derived cells lines that are deficient for a single catalytic subunit (STT3A or STT3B) or two STT3B-specific accessory subunits (MagT1 and TUSC3) 915:1073 Here, we have used the CRISPR/Cas9 gene editing technology to create viable HEK293 derived cells lines that are deficient for a single catalytic subunit (STT3A or STT3B) or two STT3B-specific accessory subunits (MagT1 and TUSC3). 26864433 2 30 theme specific 498:505 arg1 subunits 507:514 one to two complex specific subunits 479:514 one to two complex specific subunits 479:514 Metazoan organisms express two oligosaccharyltransferase complexes that are composed of a catalytic subunit (STT3A or STT3B) assembled with a shared set of accessory subunits and one to two complex specific subunits. 26864433 5 31 theme editing 886:892 arg1 technology 894:903 the CRISPR/Cas9 gene editing technology 865:903 the CRISPR/Cas9 gene editing technology 865:903 Here, we have used the CRISPR/Cas9 gene editing technology to create viable HEK293 derived cells lines that are deficient for a single catalytic subunit (STT3A or STT3B) or two STT3B-specific accessory subunits (MagT1 and TUSC3). 26864433 6 32 theme protein 1088:1094 arg1 glycosylation 1096:1108 protein glycosylation 1088:1108 protein glycosylation in the STT3A, STT3B and MagT1/TUSC3 null cell lines 1088:1160 Analysis of protein glycosylation in the STT3A, STT3B and MagT1/TUSC3 null cell lines revealed that these cell lines are superior tools for investigating the in vivo role and substrate preferences of the STT3A and STT3B complexes. 26864433 3 33 theme siRNA 517:521 arg1 knockdowns 532:541 siRNA mediated knockdowns 517:541 siRNA mediated knockdowns of STT3A and STT3B in HeLa cells 517:574 siRNA mediated knockdowns of STT3A and STT3B in HeLa cells have shown that the two OST complexes have partially non-overlapping roles in N-linked glycosylation. 26864433 3 34 link N-linked 654:661 arg1 glycosylation 663:675 N-linked glycosylation 654:675 N-linked glycosylation 654:675 siRNA mediated knockdowns of STT3A and STT3B in HeLa cells have shown that the two OST complexes have partially non-overlapping roles in N-linked glycosylation. 26864433 2 35 dep two 486:488 arg1 to 483:484 to 483:484 to 483:484 Metazoan organisms express two oligosaccharyltransferase complexes that are composed of a catalytic subunit (STT3A or STT3B) assembled with a shared set of accessory subunits and one to two complex specific subunits. 26864433 3 36 theme STT3B 556:560 arg1 knockdowns 532:541 siRNA mediated knockdowns 517:541 siRNA mediated knockdowns of STT3A and STT3B in HeLa cells 517:574 siRNA mediated knockdowns of STT3A and STT3B in HeLa cells have shown that the two OST complexes have partially non-overlapping roles in N-linked glycosylation. 26864433 3 37 theme STT3A 546:550 arg1 knockdowns 532:541 siRNA mediated knockdowns 517:541 siRNA mediated knockdowns of STT3A and STT3B in HeLa cells 517:574 siRNA mediated knockdowns of STT3A and STT3B in HeLa cells have shown that the two OST complexes have partially non-overlapping roles in N-linked glycosylation. 26864433 0 38 link linked 158:163 arg1 glycosylation 165:177 asparagine linked glycosylation 147:177 asparagine linked glycosylation 147:177 Mammalian cells lacking either the cotranslational or posttranslocational oligosaccharyltransferase complex display substrate-dependent defects in asparagine linked glycosylation. 26864433 6 39 theme cell 1151:1154 arg1 lines 1156:1160 the STT3A, STT3B and MagT1/TUSC3 null cell lines 1113:1160 the STT3A, STT3B and MagT1/TUSC3 null cell lines 1113:1160 Analysis of protein glycosylation in the STT3A, STT3B and MagT1/TUSC3 null cell lines revealed that these cell lines are superior tools for investigating the in vivo role and substrate preferences of the STT3A and STT3B complexes. 26864433 2 40 theme shared 442:447 arg1 subunits 507:514 one to two complex specific subunits 479:514 one to two complex specific subunits 479:514 Metazoan organisms express two oligosaccharyltransferase complexes that are composed of a catalytic subunit (STT3A or STT3B) assembled with a shared set of accessory subunits and one to two complex specific subunits. 26864433 2 40 theme shared 442:447 arg1 set 449:451 a shared set 440:451 a shared set of accessory subunits and one to two complex specific subunits 440:514 Metazoan organisms express two oligosaccharyltransferase complexes that are composed of a catalytic subunit (STT3A or STT3B) assembled with a shared set of accessory subunits and one to two complex specific subunits. 26864433 2 40 theme shared 442:447 arg1 subunits 466:473 accessory subunits 456:473 accessory subunits 456:473 Metazoan organisms express two oligosaccharyltransferase complexes that are composed of a catalytic subunit (STT3A or STT3B) assembled with a shared set of accessory subunits and one to two complex specific subunits. 26864433 1 41 theme essential 230:238 arg1 glycosylation 198:210 Asparagine linked glycosylation 180:210 Asparagine linked glycosylation of proteins 180:222 Asparagine linked glycosylation of proteins is an essential protein modification reaction in most eukaryotic organisms. 26864433 1 41 theme essential 230:238 arg1 reaction 261:268 an essential protein modification reaction 227:268 an essential protein modification reaction in most eukaryotic organisms 227:297 Asparagine linked glycosylation of proteins is an essential protein modification reaction in most eukaryotic organisms. 26864433 6 42 theme MagT1/TUSC3 1134:1144 arg1 lines 1156:1160 the STT3A, STT3B and MagT1/TUSC3 null cell lines 1113:1160 the STT3A, STT3B and MagT1/TUSC3 null cell lines 1113:1160 Analysis of protein glycosylation in the STT3A, STT3B and MagT1/TUSC3 null cell lines revealed that these cell lines are superior tools for investigating the in vivo role and substrate preferences of the STT3A and STT3B complexes. 26864433 3 43 theme HeLa 565:568 arg1 cells 570:574 HeLa cells 565:574 HeLa cells 565:574 siRNA mediated knockdowns of STT3A and STT3B in HeLa cells have shown that the two OST complexes have partially non-overlapping roles in N-linked glycosylation. 26864433 6 44 theme STT3B 1124:1128 arg1 lines 1156:1160 the STT3A, STT3B and MagT1/TUSC3 null cell lines 1113:1160 the STT3A, STT3B and MagT1/TUSC3 null cell lines 1113:1160 Analysis of protein glycosylation in the STT3A, STT3B and MagT1/TUSC3 null cell lines revealed that these cell lines are superior tools for investigating the in vivo role and substrate preferences of the STT3A and STT3B complexes. 26864433 6 45 theme STT3B 1290:1294 arg1 complexes 1296:1304 the STT3A and STT3B complexes 1276:1304 complexes 1296:1304 Analysis of protein glycosylation in the STT3A, STT3B and MagT1/TUSC3 null cell lines revealed that these cell lines are superior tools for investigating the in vivo role and substrate preferences of the STT3A and STT3B complexes. 26864433 1 46 theme protein 240:246 arg1 glycosylation 198:210 Asparagine linked glycosylation 180:210 Asparagine linked glycosylation of proteins 180:222 Asparagine linked glycosylation of proteins is an essential protein modification reaction in most eukaryotic organisms. 26864433 1 46 theme protein 240:246 arg1 reaction 261:268 an essential protein modification reaction 227:268 an essential protein modification reaction in most eukaryotic organisms 227:297 Asparagine linked glycosylation of proteins is an essential protein modification reaction in most eukaryotic organisms. 26864433 5 47 theme HEK293 922:927 arg1 lines 943:947 viable HEK293 derived cells lines 915:947 viable HEK293 derived cells lines that are deficient for a single catalytic subunit (STT3A or STT3B) or two STT3B-specific accessory subunits (MagT1 and TUSC3) 915:1073 Here, we have used the CRISPR/Cas9 gene editing technology to create viable HEK293 derived cells lines that are deficient for a single catalytic subunit (STT3A or STT3B) or two STT3B-specific accessory subunits (MagT1 and TUSC3). 26864433 6 48 theme superior 1197:1204 arg1 lines 1187:1191 these cell lines 1176:1191 these cell lines 1176:1191 Analysis of protein glycosylation in the STT3A, STT3B and MagT1/TUSC3 null cell lines revealed that these cell lines are superior tools for investigating the in vivo role and substrate preferences of the STT3A and STT3B complexes. 26864433 6 48 theme superior 1197:1204 arg1 tools 1206:1210 superior tools 1197:1210 superior tools for investigating the in vivo role and substrate preferences of the STT3A and STT3B complexes 1197:1304 Analysis of protein glycosylation in the STT3A, STT3B and MagT1/TUSC3 null cell lines revealed that these cell lines are superior tools for investigating the in vivo role and substrate preferences of the STT3A and STT3B complexes. 26864433 4 49 theme STT3A 726:730 arg1 depletion 713:721 incomplete siRNA mediated depletion 687:721 incomplete siRNA mediated depletion of STT3A or STT3B 687:739 However, incomplete siRNA mediated depletion of STT3A or STT3B reduces the impact of OST complex loss, thereby complicating the interpretation of experimental results. 26864433 6 50 theme STT3A 1280:1284 arg1 complexes 1296:1304 the STT3A and STT3B complexes 1276:1304 complexes 1296:1304 Analysis of protein glycosylation in the STT3A, STT3B and MagT1/TUSC3 null cell lines revealed that these cell lines are superior tools for investigating the in vivo role and substrate preferences of the STT3A and STT3B complexes. 26864433 6 51 from Analysis 1076:1083 arg1 lines 1156:1160 the STT3A, STT3B and MagT1/TUSC3 null cell lines 1113:1160 the STT3A, STT3B and MagT1/TUSC3 null cell lines 1113:1160 Analysis of protein glycosylation in the STT3A, STT3B and MagT1/TUSC3 null cell lines revealed that these cell lines are superior tools for investigating the in vivo role and substrate preferences of the STT3A and STT3B complexes. 26864433 5 52 theme cells 937:941 arg1 lines 943:947 viable HEK293 derived cells lines 915:947 viable HEK293 derived cells lines that are deficient for a single catalytic subunit (STT3A or STT3B) or two STT3B-specific accessory subunits (MagT1 and TUSC3) 915:1073 Here, we have used the CRISPR/Cas9 gene editing technology to create viable HEK293 derived cells lines that are deficient for a single catalytic subunit (STT3A or STT3B) or two STT3B-specific accessory subunits (MagT1 and TUSC3). 26864433 4 53 theme STT3B 735:739 arg1 depletion 713:721 incomplete siRNA mediated depletion 687:721 incomplete siRNA mediated depletion of STT3A or STT3B 687:739 However, incomplete siRNA mediated depletion of STT3A or STT3B reduces the impact of OST complex loss, thereby complicating the interpretation of experimental results. 26864433 2 54 theme catalytic 390:398 arg1 subunit 400:406 a catalytic subunit 388:406 a catalytic subunit (STT3A or STT3B) assembled with a shared set of accessory subunits and one to two complex specific subunits 388:514 Metazoan organisms express two oligosaccharyltransferase complexes that are composed of a catalytic subunit (STT3A or STT3B) assembled with a shared set of accessory subunits and one to two complex specific subunits. 26864433 4 55 theme siRNA 698:702 arg1 depletion 713:721 incomplete siRNA mediated depletion 687:721 incomplete siRNA mediated depletion of STT3A or STT3B 687:739 However, incomplete siRNA mediated depletion of STT3A or STT3B reduces the impact of OST complex loss, thereby complicating the interpretation of experimental results. 26864433 3 56 theme N-linked 654:661 arg1 glycosylation 663:675 N-linked glycosylation 654:675 N-linked glycosylation 654:675 siRNA mediated knockdowns of STT3A and STT3B in HeLa cells have shown that the two OST complexes have partially non-overlapping roles in N-linked glycosylation. 26864433 1 57 theme most 273:276 arg1 organisms 289:297 most eukaryotic organisms 273:297 most eukaryotic organisms 273:297 Asparagine linked glycosylation of proteins is an essential protein modification reaction in most eukaryotic organisms. 26864433 5 58 dep subunits 1048:1055 arg1 TUSC3 1068:1072 TUSC3 1068:1072 TUSC3 1068:1072 Here, we have used the CRISPR/Cas9 gene editing technology to create viable HEK293 derived cells lines that are deficient for a single catalytic subunit (STT3A or STT3B) or two STT3B-specific accessory subunits (MagT1 and TUSC3). 26864433 5 58 dep subunits 1048:1055 arg1 MagT1 1058:1062 MagT1 1058:1062 MagT1 1058:1062 Here, we have used the CRISPR/Cas9 gene editing technology to create viable HEK293 derived cells lines that are deficient for a single catalytic subunit (STT3A or STT3B) or two STT3B-specific accessory subunits (MagT1 and TUSC3). 26864433 5 58 dep subunits 1048:1055 arg1 subunits 1048:1055 two STT3B-specific accessory subunits 1019:1055 two STT3B-specific accessory subunits (MagT1 and TUSC3) 1019:1073 Here, we have used the CRISPR/Cas9 gene editing technology to create viable HEK293 derived cells lines that are deficient for a single catalytic subunit (STT3A or STT3B) or two STT3B-specific accessory subunits (MagT1 and TUSC3). 26864433 4 59 theme complex 767:773 arg1 loss 775:778 OST complex loss 763:778 OST complex loss 763:778 However, incomplete siRNA mediated depletion of STT3A or STT3B reduces the impact of OST complex loss, thereby complicating the interpretation of experimental results. 26864433 5 60 theme catalytic 981:989 arg1 subunit 991:997 a single catalytic subunit 972:997 a single catalytic subunit (STT3A or STT3B) 972:1014 Here, we have used the CRISPR/Cas9 gene editing technology to create viable HEK293 derived cells lines that are deficient for a single catalytic subunit (STT3A or STT3B) or two STT3B-specific accessory subunits (MagT1 and TUSC3). 26864433 2 61 dep subunit 400:406 arg1 STT3B 418:422 STT3B 418:422 STT3B 418:422 Metazoan organisms express two oligosaccharyltransferase complexes that are composed of a catalytic subunit (STT3A or STT3B) assembled with a shared set of accessory subunits and one to two complex specific subunits. 26864433 2 61 dep subunit 400:406 arg1 STT3A 409:413 STT3A 409:413 STT3A 409:413 Metazoan organisms express two oligosaccharyltransferase complexes that are composed of a catalytic subunit (STT3A or STT3B) assembled with a shared set of accessory subunits and one to two complex specific subunits. 26864433 5 62 dep subunit 991:997 arg1 STT3B 1009:1013 STT3B 1009:1013 STT3B 1009:1013 Here, we have used the CRISPR/Cas9 gene editing technology to create viable HEK293 derived cells lines that are deficient for a single catalytic subunit (STT3A or STT3B) or two STT3B-specific accessory subunits (MagT1 and TUSC3). 26864433 5 62 dep subunit 991:997 arg1 STT3A 1000:1004 STT3A 1000:1004 STT3A 1000:1004 Here, we have used the CRISPR/Cas9 gene editing technology to create viable HEK293 derived cells lines that are deficient for a single catalytic subunit (STT3A or STT3B) or two STT3B-specific accessory subunits (MagT1 and TUSC3). 26864433 0 63 theme substrate-dependent 116:134 arg1 defects 136:142 substrate-dependent defects 116:142 substrate-dependent defects in asparagine linked glycosylation 116:177 Mammalian cells lacking either the cotranslational or posttranslocational oligosaccharyltransferase complex display substrate-dependent defects in asparagine linked glycosylation. 26864433 1 64 theme proteins 215:222 arg1 reaction 261:268 an essential protein modification reaction 227:268 an essential protein modification reaction in most eukaryotic organisms 227:297 Asparagine linked glycosylation of proteins is an essential protein modification reaction in most eukaryotic organisms. 26864433 1 64 theme proteins 215:222 arg1 glycosylation 198:210 Asparagine linked glycosylation 180:210 Asparagine linked glycosylation of proteins 180:222 Asparagine linked glycosylation of proteins is an essential protein modification reaction in most eukaryotic organisms. 26864433 0 65 dep linked 158:163 arg1 asparagine 147:156 asparagine 147:156 asparagine 147:156 Mammalian cells lacking either the cotranslational or posttranslocational oligosaccharyltransferase complex display substrate-dependent defects in asparagine linked glycosylation. 26864433 4 66 theme experimental 824:835 arg1 results 837:843 experimental results 824:843 experimental results 824:843 However, incomplete siRNA mediated depletion of STT3A or STT3B reduces the impact of OST complex loss, thereby complicating the interpretation of experimental results. 26864433 1 67 dep linked 191:196 arg1 Asparagine 180:189 Asparagine 180:189 Asparagine 180:189 Asparagine linked glycosylation of proteins is an essential protein modification reaction in most eukaryotic organisms. 26864433 0 68 theme linked 158:163 arg1 glycosylation 165:177 asparagine linked glycosylation 147:177 asparagine linked glycosylation 147:177 Mammalian cells lacking either the cotranslational or posttranslocational oligosaccharyltransferase complex display substrate-dependent defects in asparagine linked glycosylation. 26864433 2 69 theme accessory 456:464 arg1 subunits 466:473 accessory subunits 456:473 accessory subunits 456:473 Metazoan organisms express two oligosaccharyltransferase complexes that are composed of a catalytic subunit (STT3A or STT3B) assembled with a shared set of accessory subunits and one to two complex specific subunits. 26864433 2 70 theme subunits 507:514 arg1 subunits 507:514 one to two complex specific subunits 479:514 one to two complex specific subunits 479:514 Metazoan organisms express two oligosaccharyltransferase complexes that are composed of a catalytic subunit (STT3A or STT3B) assembled with a shared set of accessory subunits and one to two complex specific subunits. 26864433 2 70 theme subunits 507:514 arg1 set 449:451 a shared set 440:451 a shared set of accessory subunits and one to two complex specific subunits 440:514 Metazoan organisms express two oligosaccharyltransferase complexes that are composed of a catalytic subunit (STT3A or STT3B) assembled with a shared set of accessory subunits and one to two complex specific subunits. 26864433 2 70 theme subunits 507:514 arg1 subunits 466:473 accessory subunits 456:473 accessory subunits 456:473 Metazoan organisms express two oligosaccharyltransferase complexes that are composed of a catalytic subunit (STT3A or STT3B) assembled with a shared set of accessory subunits and one to two complex specific subunits. 26864433 3 71 contain have 614:617 arg2 roles 645:649 partially non-overlapping roles 619:649 partially non-overlapping roles 619:649 siRNA mediated knockdowns of STT3A and STT3B in HeLa cells have shown that the two OST complexes have partially non-overlapping roles in N-linked glycosylation. 26864433 3 71 contain have 614:617 arg1 complexes 604:612 the two OST complexes 592:612 the two OST complexes 592:612 siRNA mediated knockdowns of STT3A and STT3B in HeLa cells have shown that the two OST complexes have partially non-overlapping roles in N-linked glycosylation. 26864433 5 72 theme gene 881:884 arg1 technology 894:903 the CRISPR/Cas9 gene editing technology 865:903 the CRISPR/Cas9 gene editing technology 865:903 Here, we have used the CRISPR/Cas9 gene editing technology to create viable HEK293 derived cells lines that are deficient for a single catalytic subunit (STT3A or STT3B) or two STT3B-specific accessory subunits (MagT1 and TUSC3). 26864433 5 73 used used 860:863 arg2 we 852:853 we 852:853 we 852:853 Here, we have used the CRISPR/Cas9 gene editing technology to create viable HEK293 derived cells lines that are deficient for a single catalytic subunit (STT3A or STT3B) or two STT3B-specific accessory subunits (MagT1 and TUSC3). 26864433 0 74 dep complex 100:106 arg1 either 24:29 either 24:29 either 24:29 Mammalian cells lacking either the cotranslational or posttranslocational oligosaccharyltransferase complex display substrate-dependent defects in asparagine linked glycosylation. 26864433 6 75 theme glycosylation 1096:1108 arg1 Analysis 1076:1083 Analysis 1076:1083 Analysis of protein glycosylation in the STT3A, STT3B and MagT1/TUSC3 null cell lines 1076:1160 Analysis of protein glycosylation in the STT3A, STT3B and MagT1/TUSC3 null cell lines revealed that these cell lines are superior tools for investigating the in vivo role and substrate preferences of the STT3A and STT3B complexes. 26864433 2 76 theme complex 490:496 arg1 subunits 507:514 one to two complex specific subunits 479:514 one to two complex specific subunits 479:514 Metazoan organisms express two oligosaccharyltransferase complexes that are composed of a catalytic subunit (STT3A or STT3B) assembled with a shared set of accessory subunits and one to two complex specific subunits. 26864433 6 77 gly glycosylation 1096:1108 arg1 lines 1156:1160 the STT3A, STT3B and MagT1/TUSC3 null cell lines 1113:1160 the STT3A, STT3B and MagT1/TUSC3 null cell lines 1113:1160 Analysis of protein glycosylation in the STT3A, STT3B and MagT1/TUSC3 null cell lines revealed that these cell lines are superior tools for investigating the in vivo role and substrate preferences of the STT3A and STT3B complexes. 26864433 0 78 theme cotranslational 35:49 arg1 complex 100:106 either the cotranslational or posttranslocational oligosaccharyltransferase complex 24:106 complex 100:106 Mammalian cells lacking either the cotranslational or posttranslocational oligosaccharyltransferase complex display substrate-dependent defects in asparagine linked glycosylation. 26864433 6 79 from lines 1156:1160 arg1 Analysis 1076:1083 Analysis 1076:1083 Analysis of protein glycosylation in the STT3A, STT3B and MagT1/TUSC3 null cell lines 1076:1160 Analysis of protein glycosylation in the STT3A, STT3B and MagT1/TUSC3 null cell lines revealed that these cell lines are superior tools for investigating the in vivo role and substrate preferences of the STT3A and STT3B complexes. 26864433 3 80 theme mediated 523:530 arg1 knockdowns 532:541 siRNA mediated knockdowns 517:541 siRNA mediated knockdowns of STT3A and STT3B in HeLa cells 517:574 siRNA mediated knockdowns of STT3A and STT3B in HeLa cells have shown that the two OST complexes have partially non-overlapping roles in N-linked glycosylation. 26864433 0 81 theme posttranslocational 54:72 arg1 complex 100:106 either the cotranslational or posttranslocational oligosaccharyltransferase complex 24:106 complex 100:106 Mammalian cells lacking either the cotranslational or posttranslocational oligosaccharyltransferase complex display substrate-dependent defects in asparagine linked glycosylation. 26864433 1 82 link linked 191:196 arg1 reaction 261:268 an essential protein modification reaction 227:268 an essential protein modification reaction in most eukaryotic organisms 227:297 Asparagine linked glycosylation of proteins is an essential protein modification reaction in most eukaryotic organisms. 26864433 1 82 link linked 191:196 arg1 glycosylation 198:210 Asparagine linked glycosylation 180:210 Asparagine linked glycosylation of proteins 180:222 Asparagine linked glycosylation of proteins is an essential protein modification reaction in most eukaryotic organisms. 26864433 3 83 from knockdowns 532:541 arg1 cells 570:574 HeLa cells 565:574 HeLa cells 565:574 siRNA mediated knockdowns of STT3A and STT3B in HeLa cells have shown that the two OST complexes have partially non-overlapping roles in N-linked glycosylation. 26864433 5 84 theme accessory 1038:1046 arg1 TUSC3 1068:1072 TUSC3 1068:1072 TUSC3 1068:1072 Here, we have used the CRISPR/Cas9 gene editing technology to create viable HEK293 derived cells lines that are deficient for a single catalytic subunit (STT3A or STT3B) or two STT3B-specific accessory subunits (MagT1 and TUSC3). 26864433 5 84 theme accessory 1038:1046 arg1 MagT1 1058:1062 MagT1 1058:1062 MagT1 1058:1062 Here, we have used the CRISPR/Cas9 gene editing technology to create viable HEK293 derived cells lines that are deficient for a single catalytic subunit (STT3A or STT3B) or two STT3B-specific accessory subunits (MagT1 and TUSC3). 26864433 5 84 theme accessory 1038:1046 arg1 subunits 1048:1055 two STT3B-specific accessory subunits 1019:1055 two STT3B-specific accessory subunits (MagT1 and TUSC3) 1019:1073 Here, we have used the CRISPR/Cas9 gene editing technology to create viable HEK293 derived cells lines that are deficient for a single catalytic subunit (STT3A or STT3B) or two STT3B-specific accessory subunits (MagT1 and TUSC3). 26864433 1 85 theme eukaryotic 278:287 arg1 organisms 289:297 most eukaryotic organisms 273:297 most eukaryotic organisms 273:297 Asparagine linked glycosylation of proteins is an essential protein modification reaction in most eukaryotic organisms. 26864433 6 86 theme null 1146:1149 arg1 lines 1156:1160 the STT3A, STT3B and MagT1/TUSC3 null cell lines 1113:1160 the STT3A, STT3B and MagT1/TUSC3 null cell lines 1113:1160 Analysis of protein glycosylation in the STT3A, STT3B and MagT1/TUSC3 null cell lines revealed that these cell lines are superior tools for investigating the in vivo role and substrate preferences of the STT3A and STT3B complexes. 26864433 4 87 theme incomplete 687:696 arg1 depletion 713:721 incomplete siRNA mediated depletion 687:721 incomplete siRNA mediated depletion of STT3A or STT3B 687:739 However, incomplete siRNA mediated depletion of STT3A or STT3B reduces the impact of OST complex loss, thereby complicating the interpretation of experimental results. 26399494 0 0 theme PNGase 89:94 arg1 Deglycosylation 98:112 Hydroxylamine Assisted PNGase F Deglycosylation 66:112 Hydroxylamine Assisted PNGase F Deglycosylation for N-Glycoproteome Analysis 66:141 Highly Efficient Release of Glycopeptides from Hydrazide Beads by Hydroxylamine Assisted PNGase F Deglycosylation for N-Glycoproteome Analysis. 26399494 2 1 theme numerous 536:543 arg1 interests 545:553 numerous interests 536:553 numerous interests 536:553 On account of the high enrichment specificity, hydrazide chemistry based solid-phase extraction of N-linked glycopeptides technique has sparked numerous interests. 26399494 4 2 theme hydrazone 944:952 arg1 bonds 954:958 hydrazone bonds 944:958 hydrazone bonds 944:958 In this study, we developed a hydroxylamine assisted PNGase F deglycosylation (HAPD) method using the hydroxylamine to release glycopeptides captured on the hydrazide beads through the cleavage of hydrazone bonds by transamination followed with the PNGase F deglycosylation of the released glycopeptides in the free solution. 26399494 4 3 from deglycosylation 1005:1019 arg1 solution 1063:1070 the free solution 1054:1070 the free solution 1054:1070 In this study, we developed a hydroxylamine assisted PNGase F deglycosylation (HAPD) method using the hydroxylamine to release glycopeptides captured on the hydrazide beads through the cleavage of hydrazone bonds by transamination followed with the PNGase F deglycosylation of the released glycopeptides in the free solution. 26399494 0 4 theme Assisted 80:87 arg1 Deglycosylation 98:112 Hydroxylamine Assisted PNGase F Deglycosylation 66:112 Hydroxylamine Assisted PNGase F Deglycosylation for N-Glycoproteome Analysis 66:141 Highly Efficient Release of Glycopeptides from Hydrazide Beads by Hydroxylamine Assisted PNGase F Deglycosylation for N-Glycoproteome Analysis. 26399494 1 5 theme comprehensive 354:366 arg1 analysis 382:389 comprehensive glycoproteome analysis 354:389 comprehensive glycoproteome analysis 354:389 Selective enrichment of glycopeptides from complex sample followed by cleavage of N-glycans by PNGase F to expose an easily detectable mark on the former glycosylation sites has become the popular protocol for comprehensive glycoproteome analysis. 26399494 4 6 theme hydrazide 904:912 arg1 beads 914:918 the hydrazide beads 900:918 the hydrazide beads 900:918 In this study, we developed a hydroxylamine assisted PNGase F deglycosylation (HAPD) method using the hydroxylamine to release glycopeptides captured on the hydrazide beads through the cleavage of hydrazone bonds by transamination followed with the PNGase F deglycosylation of the released glycopeptides in the free solution. 26399494 1 7 theme complex 187:193 arg1 sample 195:200 complex sample 187:200 complex sample followed by cleavage of N-glycans by PNGase F to expose an easily detectable mark on the former glycosylation sites 187:316 Selective enrichment of glycopeptides from complex sample followed by cleavage of N-glycans by PNGase F to expose an easily detectable mark on the former glycosylation sites has become the popular protocol for comprehensive glycoproteome analysis. 26399494 7 8 theme glycosylated 1391:1402 arg1 peptides 1404:1411 identified N-terminal glycosylated peptides 1369:1411 identified N-terminal glycosylated peptides 1369:1411 Moreover, the ratio of identified N-terminal glycosylated peptides was improved over 5-fold. 26399494 4 9 theme PNGase 996:1001 arg1 deglycosylation 1005:1019 the PNGase F deglycosylation 992:1019 the PNGase F deglycosylation of the released glycopeptides in the free solution 992:1070 In this study, we developed a hydroxylamine assisted PNGase F deglycosylation (HAPD) method using the hydroxylamine to release glycopeptides captured on the hydrazide beads through the cleavage of hydrazone bonds by transamination followed with the PNGase F deglycosylation of the released glycopeptides in the free solution. 26399494 1 10 theme glycoproteome 368:380 arg1 analysis 382:389 comprehensive glycoproteome analysis 354:389 comprehensive glycoproteome analysis 354:389 Selective enrichment of glycopeptides from complex sample followed by cleavage of N-glycans by PNGase F to expose an easily detectable mark on the former glycosylation sites has become the popular protocol for comprehensive glycoproteome analysis. 26399494 4 11 theme release 866:872 arg1 glycopeptides 874:886 the hydroxylamine to release glycopeptides 845:886 the hydroxylamine to release glycopeptides captured on the hydrazide beads through the cleavage of hydrazone bonds by transamination followed with the PNGase F deglycosylation of the released glycopeptides in the free solution 845:1070 In this study, we developed a hydroxylamine assisted PNGase F deglycosylation (HAPD) method using the hydroxylamine to release glycopeptides captured on the hydrazide beads through the cleavage of hydrazone bonds by transamination followed with the PNGase F deglycosylation of the released glycopeptides in the free solution. 26399494 3 12 theme glycopeptides 590:602 arg1 efficient 692:700 efficient 692:700 efficient 692:700 However, the enzymatic release of glycopeptides captured by hydrazide beads through direct incubation of the beads with PNGase F is not efficient due to the inherent steric hindrance effect. 26399494 3 12 theme glycopeptides 590:602 arg1 release 579:585 the enzymatic release 565:585 the enzymatic release of glycopeptides captured by hydrazide beads through direct incubation of the beads with PNGase F 565:683 However, the enzymatic release of glycopeptides captured by hydrazide beads through direct incubation of the beads with PNGase F is not efficient due to the inherent steric hindrance effect. 26399494 4 13 gly deglycosylation 1005:1019 arg1 glycopeptides 1037:1049 the released glycopeptides 1024:1049 the released glycopeptides in the free solution 1024:1070 In this study, we developed a hydroxylamine assisted PNGase F deglycosylation (HAPD) method using the hydroxylamine to release glycopeptides captured on the hydrazide beads through the cleavage of hydrazone bonds by transamination followed with the PNGase F deglycosylation of the released glycopeptides in the free solution. 26399494 4 14 theme F 1003:1003 arg1 deglycosylation 1005:1019 the PNGase F deglycosylation 992:1019 the PNGase F deglycosylation of the released glycopeptides in the free solution 992:1070 In this study, we developed a hydroxylamine assisted PNGase F deglycosylation (HAPD) method using the hydroxylamine to release glycopeptides captured on the hydrazide beads through the cleavage of hydrazone bonds by transamination followed with the PNGase F deglycosylation of the released glycopeptides in the free solution. 26399494 0 15 theme F 96:96 arg1 Deglycosylation 98:112 Hydroxylamine Assisted PNGase F Deglycosylation 66:112 Hydroxylamine Assisted PNGase F Deglycosylation for N-Glycoproteome Analysis 66:141 Highly Efficient Release of Glycopeptides from Hydrazide Beads by Hydroxylamine Assisted PNGase F Deglycosylation for N-Glycoproteome Analysis. 26399494 0 16 from Beads 57:61 arg1 Release 17:23 Highly Efficient Release 0:23 Highly Efficient Release of Glycopeptides from Hydrazide Beads by Hydroxylamine Assisted PNGase F Deglycosylation for N-Glycoproteome Analysis. 0:142 Highly Efficient Release of Glycopeptides from Hydrazide Beads by Hydroxylamine Assisted PNGase F Deglycosylation for N-Glycoproteome Analysis. 26399494 6 17 theme conventional 1325:1336 arg1 method 1338:1343 the conventional method 1321:1343 the conventional method 1321:1343 It was found that 27% more N-glycosylation sites were identified by the HAPD strategy compared with the conventional method. 26399494 4 18 theme PNGase 800:805 arg1 method 832:837 a hydroxylamine assisted PNGase F deglycosylation (HAPD) method 775:837 a hydroxylamine assisted PNGase F deglycosylation (HAPD) method using the hydroxylamine to release glycopeptides captured on the hydrazide beads through the cleavage of hydrazone bonds by transamination followed with the PNGase F deglycosylation of the released glycopeptides in the free solution 775:1070 In this study, we developed a hydroxylamine assisted PNGase F deglycosylation (HAPD) method using the hydroxylamine to release glycopeptides captured on the hydrazide beads through the cleavage of hydrazone bonds by transamination followed with the PNGase F deglycosylation of the released glycopeptides in the free solution. 26399494 4 19 theme free 1058:1061 arg1 solution 1063:1070 the free solution 1054:1070 the free solution 1054:1070 In this study, we developed a hydroxylamine assisted PNGase F deglycosylation (HAPD) method using the hydroxylamine to release glycopeptides captured on the hydrazide beads through the cleavage of hydrazone bonds by transamination followed with the PNGase F deglycosylation of the released glycopeptides in the free solution. 26399494 0 20 theme N-Glycoproteome 118:132 arg1 Analysis 134:141 N-Glycoproteome Analysis 118:141 N-Glycoproteome Analysis 118:141 Highly Efficient Release of Glycopeptides from Hydrazide Beads by Hydroxylamine Assisted PNGase F Deglycosylation for N-Glycoproteome Analysis. 26399494 5 21 theme deglycosylated 1151:1164 arg1 peptides 1166:1173 deglycosylated peptides 1151:1173 deglycosylated peptides (deglycopeptides) 1151:1191 Because of the homogeneous condition for the deglycosylation, the recovery of deglycosylated peptides (deglycopeptides) was improved significantly. 26399494 5 21 theme deglycosylated 1151:1164 arg1 deglycopeptides 1176:1190 deglycopeptides 1176:1190 deglycopeptides 1176:1190 Because of the homogeneous condition for the deglycosylation, the recovery of deglycosylated peptides (deglycopeptides) was improved significantly. 26399494 2 22 theme hydrazide 439:447 arg1 technique 514:522 hydrazide chemistry based solid-phase extraction of N-linked glycopeptides technique 439:522 hydrazide chemistry based solid-phase extraction of N-linked glycopeptides technique 439:522 On account of the high enrichment specificity, hydrazide chemistry based solid-phase extraction of N-linked glycopeptides technique has sparked numerous interests. 26399494 4 23 theme HAPD 826:829 arg1 method 832:837 a hydroxylamine assisted PNGase F deglycosylation (HAPD) method 775:837 a hydroxylamine assisted PNGase F deglycosylation (HAPD) method using the hydroxylamine to release glycopeptides captured on the hydrazide beads through the cleavage of hydrazone bonds by transamination followed with the PNGase F deglycosylation of the released glycopeptides in the free solution 775:1070 In this study, we developed a hydroxylamine assisted PNGase F deglycosylation (HAPD) method using the hydroxylamine to release glycopeptides captured on the hydrazide beads through the cleavage of hydrazone bonds by transamination followed with the PNGase F deglycosylation of the released glycopeptides in the free solution. 26399494 2 24 theme enrichment 415:424 arg1 specificity 426:436 the high enrichment specificity 406:436 the high enrichment specificity 406:436 On account of the high enrichment specificity, hydrazide chemistry based solid-phase extraction of N-linked glycopeptides technique has sparked numerous interests. 26399494 2 25 theme N-linked 491:498 arg1 glycopeptides 500:512 N-linked glycopeptides 491:512 N-linked glycopeptides 491:512 On account of the high enrichment specificity, hydrazide chemistry based solid-phase extraction of N-linked glycopeptides technique has sparked numerous interests. 26399494 5 26 theme peptides 1166:1173 arg1 recovery 1139:1146 the recovery 1135:1146 the recovery of deglycosylated peptides (deglycopeptides) 1135:1191 Because of the homogeneous condition for the deglycosylation, the recovery of deglycosylated peptides (deglycopeptides) was improved significantly. 26399494 7 27 gly glycosylated 1391:1402 arg1 peptides 1404:1411 identified N-terminal glycosylated peptides 1369:1411 identified N-terminal glycosylated peptides 1369:1411 Moreover, the ratio of identified N-terminal glycosylated peptides was improved over 5-fold. 26399494 4 28 gly glycopeptides 1037:1049 arg2 glycopeptides 1037:1049 the released glycopeptides 1024:1049 the released glycopeptides in the free solution 1024:1070 In this study, we developed a hydroxylamine assisted PNGase F deglycosylation (HAPD) method using the hydroxylamine to release glycopeptides captured on the hydrazide beads through the cleavage of hydrazone bonds by transamination followed with the PNGase F deglycosylation of the released glycopeptides in the free solution. 26399494 2 29 theme high 410:413 arg1 specificity 426:436 the high enrichment specificity 406:436 the high enrichment specificity 406:436 On account of the high enrichment specificity, hydrazide chemistry based solid-phase extraction of N-linked glycopeptides technique has sparked numerous interests. 26399494 0 30 theme Efficient 7:15 arg1 Release 17:23 Highly Efficient Release 0:23 Highly Efficient Release of Glycopeptides from Hydrazide Beads by Hydroxylamine Assisted PNGase F Deglycosylation for N-Glycoproteome Analysis. 0:142 Highly Efficient Release of Glycopeptides from Hydrazide Beads by Hydroxylamine Assisted PNGase F Deglycosylation for N-Glycoproteome Analysis. 26399494 3 31 theme enzymatic 569:577 arg1 efficient 692:700 efficient 692:700 efficient 692:700 However, the enzymatic release of glycopeptides captured by hydrazide beads through direct incubation of the beads with PNGase F is not efficient due to the inherent steric hindrance effect. 26399494 3 31 theme enzymatic 569:577 arg1 release 579:585 the enzymatic release 565:585 the enzymatic release of glycopeptides captured by hydrazide beads through direct incubation of the beads with PNGase F 565:683 However, the enzymatic release of glycopeptides captured by hydrazide beads through direct incubation of the beads with PNGase F is not efficient due to the inherent steric hindrance effect. 26399494 2 32 link N-linked 491:498 arg1 glycopeptides 500:512 N-linked glycopeptides 491:512 N-linked glycopeptides 491:512 On account of the high enrichment specificity, hydrazide chemistry based solid-phase extraction of N-linked glycopeptides technique has sparked numerous interests. 26399494 7 33 theme identified 1369:1378 arg1 peptides 1404:1411 identified N-terminal glycosylated peptides 1369:1411 identified N-terminal glycosylated peptides 1369:1411 Moreover, the ratio of identified N-terminal glycosylated peptides was improved over 5-fold. 26399494 2 34 theme extraction 477:486 arg1 technique 514:522 hydrazide chemistry based solid-phase extraction of N-linked glycopeptides technique 439:522 hydrazide chemistry based solid-phase extraction of N-linked glycopeptides technique 439:522 On account of the high enrichment specificity, hydrazide chemistry based solid-phase extraction of N-linked glycopeptides technique has sparked numerous interests. 26399494 6 35 theme N-glycosylation 1248:1262 arg1 sites 1264:1268 27% more N-glycosylation sites 1239:1268 27% more N-glycosylation sites 1239:1268 It was found that 27% more N-glycosylation sites were identified by the HAPD strategy compared with the conventional method. 26399494 5 36 theme homogeneous 1088:1098 arg1 condition 1100:1108 the homogeneous condition 1084:1108 the homogeneous condition for the deglycosylation 1084:1132 Because of the homogeneous condition for the deglycosylation, the recovery of deglycosylated peptides (deglycopeptides) was improved significantly. 26399494 5 37 gly deglycosylated 1151:1164 arg1 peptides 1166:1173 deglycosylated peptides 1151:1173 deglycosylated peptides (deglycopeptides) 1151:1191 Because of the homogeneous condition for the deglycosylation, the recovery of deglycosylated peptides (deglycopeptides) was improved significantly. 26399494 5 37 gly deglycosylated 1151:1164 arg1 deglycopeptides 1176:1190 deglycopeptides 1176:1190 deglycopeptides 1176:1190 Because of the homogeneous condition for the deglycosylation, the recovery of deglycosylated peptides (deglycopeptides) was improved significantly. 26399494 7 38 theme N-terminal 1380:1389 arg1 peptides 1404:1411 identified N-terminal glycosylated peptides 1369:1411 identified N-terminal glycosylated peptides 1369:1411 Moreover, the ratio of identified N-terminal glycosylated peptides was improved over 5-fold. 26399494 2 39 theme solid-phase 465:475 arg1 extraction 477:486 solid-phase extraction 465:486 hydrazide chemistry based solid-phase extraction of N-linked glycopeptides technique 439:522 On account of the high enrichment specificity, hydrazide chemistry based solid-phase extraction of N-linked glycopeptides technique has sparked numerous interests. 26399494 1 40 theme former 291:296 arg1 sites 312:316 the former glycosylation sites 287:316 the former glycosylation sites 287:316 Selective enrichment of glycopeptides from complex sample followed by cleavage of N-glycans by PNGase F to expose an easily detectable mark on the former glycosylation sites has become the popular protocol for comprehensive glycoproteome analysis. 26399494 4 41 theme assisted 791:798 arg1 method 832:837 a hydroxylamine assisted PNGase F deglycosylation (HAPD) method 775:837 a hydroxylamine assisted PNGase F deglycosylation (HAPD) method using the hydroxylamine to release glycopeptides captured on the hydrazide beads through the cleavage of hydrazone bonds by transamination followed with the PNGase F deglycosylation of the released glycopeptides in the free solution 775:1070 In this study, we developed a hydroxylamine assisted PNGase F deglycosylation (HAPD) method using the hydroxylamine to release glycopeptides captured on the hydrazide beads through the cleavage of hydrazone bonds by transamination followed with the PNGase F deglycosylation of the released glycopeptides in the free solution. 26399494 6 42 theme HAPD 1293:1296 arg1 strategy 1298:1305 the HAPD strategy 1289:1305 the HAPD strategy 1289:1305 It was found that 27% more N-glycosylation sites were identified by the HAPD strategy compared with the conventional method. 26399494 2 43 theme chemistry 449:457 arg1 technique 514:522 hydrazide chemistry based solid-phase extraction of N-linked glycopeptides technique 439:522 hydrazide chemistry based solid-phase extraction of N-linked glycopeptides technique 439:522 On account of the high enrichment specificity, hydrazide chemistry based solid-phase extraction of N-linked glycopeptides technique has sparked numerous interests. 26399494 2 44 theme based 459:463 arg1 technique 514:522 hydrazide chemistry based solid-phase extraction of N-linked glycopeptides technique 439:522 hydrazide chemistry based solid-phase extraction of N-linked glycopeptides technique 439:522 On account of the high enrichment specificity, hydrazide chemistry based solid-phase extraction of N-linked glycopeptides technique has sparked numerous interests. 26399494 1 45 theme glycosylation 298:310 arg1 sites 312:316 the former glycosylation sites 287:316 the former glycosylation sites 287:316 Selective enrichment of glycopeptides from complex sample followed by cleavage of N-glycans by PNGase F to expose an easily detectable mark on the former glycosylation sites has become the popular protocol for comprehensive glycoproteome analysis. 26399494 3 46 theme hydrazide 616:624 arg1 beads 626:630 hydrazide beads 616:630 hydrazide beads 616:630 However, the enzymatic release of glycopeptides captured by hydrazide beads through direct incubation of the beads with PNGase F is not efficient due to the inherent steric hindrance effect. 26399494 1 47 theme N-glycans 226:234 arg1 cleavage 214:221 cleavage 214:221 cleavage of N-glycans 214:234 Selective enrichment of glycopeptides from complex sample followed by cleavage of N-glycans by PNGase F to expose an easily detectable mark on the former glycosylation sites has become the popular protocol for comprehensive glycoproteome analysis. 26399494 5 48 gly deglycopeptides 1176:1190 arg2 deglycopeptides 1176:1190 deglycopeptides 1176:1190 deglycopeptides 1176:1190 Because of the homogeneous condition for the deglycosylation, the recovery of deglycosylated peptides (deglycopeptides) was improved significantly. 26399494 5 48 gly deglycopeptides 1176:1190 arg2 peptides 1166:1173 deglycosylated peptides 1151:1173 deglycosylated peptides (deglycopeptides) 1151:1191 Because of the homogeneous condition for the deglycosylation, the recovery of deglycosylated peptides (deglycopeptides) was improved significantly. 26399494 4 49 theme hydroxylamine 849:861 arg1 glycopeptides 874:886 the hydroxylamine to release glycopeptides 845:886 the hydroxylamine to release glycopeptides captured on the hydrazide beads through the cleavage of hydrazone bonds by transamination followed with the PNGase F deglycosylation of the released glycopeptides in the free solution 845:1070 In this study, we developed a hydroxylamine assisted PNGase F deglycosylation (HAPD) method using the hydroxylamine to release glycopeptides captured on the hydrazide beads through the cleavage of hydrazone bonds by transamination followed with the PNGase F deglycosylation of the released glycopeptides in the free solution. 26399494 6 50 theme more 1243:1246 arg1 sites 1264:1268 27% more N-glycosylation sites 1239:1268 27% more N-glycosylation sites 1239:1268 It was found that 27% more N-glycosylation sites were identified by the HAPD strategy compared with the conventional method. 26399494 0 51 theme Glycopeptides 28:40 arg1 Release 17:23 Highly Efficient Release 0:23 Highly Efficient Release of Glycopeptides from Hydrazide Beads by Hydroxylamine Assisted PNGase F Deglycosylation for N-Glycoproteome Analysis. 0:142 Highly Efficient Release of Glycopeptides from Hydrazide Beads by Hydroxylamine Assisted PNGase F Deglycosylation for N-Glycoproteome Analysis. 26399494 4 52 theme released 1028:1035 arg1 glycopeptides 1037:1049 the released glycopeptides 1024:1049 the released glycopeptides in the free solution 1024:1070 In this study, we developed a hydroxylamine assisted PNGase F deglycosylation (HAPD) method using the hydroxylamine to release glycopeptides captured on the hydrazide beads through the cleavage of hydrazone bonds by transamination followed with the PNGase F deglycosylation of the released glycopeptides in the free solution. 26399494 1 53 dep F 246:246 arg1 expose 251:256 expose 251:256 to expose an easily detectable mark on the former glycosylation sites 248:316 Selective enrichment of glycopeptides from complex sample followed by cleavage of N-glycans by PNGase F to expose an easily detectable mark on the former glycosylation sites has become the popular protocol for comprehensive glycoproteome analysis. 26399494 1 54 theme PNGase 239:244 arg1 F 246:246 PNGase F 239:246 PNGase F to expose an easily detectable mark on the former glycosylation sites 239:316 Selective enrichment of glycopeptides from complex sample followed by cleavage of N-glycans by PNGase F to expose an easily detectable mark on the former glycosylation sites has become the popular protocol for comprehensive glycoproteome analysis. 26399494 2 55 theme glycopeptides 500:512 arg1 extraction 477:486 solid-phase extraction 465:486 hydrazide chemistry based solid-phase extraction of N-linked glycopeptides technique 439:522 On account of the high enrichment specificity, hydrazide chemistry based solid-phase extraction of N-linked glycopeptides technique has sparked numerous interests. 26399494 4 56 from solution 1063:1070 arg1 deglycosylation 1005:1019 the PNGase F deglycosylation 992:1019 the PNGase F deglycosylation of the released glycopeptides in the free solution 992:1070 In this study, we developed a hydroxylamine assisted PNGase F deglycosylation (HAPD) method using the hydroxylamine to release glycopeptides captured on the hydrazide beads through the cleavage of hydrazone bonds by transamination followed with the PNGase F deglycosylation of the released glycopeptides in the free solution. 26399494 1 57 gly glycopeptides 168:180 arg2 glycopeptides 168:180 glycopeptides 168:180 glycopeptides 168:180 Selective enrichment of glycopeptides from complex sample followed by cleavage of N-glycans by PNGase F to expose an easily detectable mark on the former glycosylation sites has become the popular protocol for comprehensive glycoproteome analysis. 26399494 3 58 theme direct 640:645 arg1 incubation 647:656 direct incubation 640:656 direct incubation of the beads with PNGase F 640:683 However, the enzymatic release of glycopeptides captured by hydrazide beads through direct incubation of the beads with PNGase F is not efficient due to the inherent steric hindrance effect. 26399494 4 59 theme bonds 954:958 arg1 cleavage 932:939 the cleavage 928:939 the cleavage of hydrazone bonds by transamination followed with the PNGase F deglycosylation of the released glycopeptides in the free solution 928:1070 In this study, we developed a hydroxylamine assisted PNGase F deglycosylation (HAPD) method using the hydroxylamine to release glycopeptides captured on the hydrazide beads through the cleavage of hydrazone bonds by transamination followed with the PNGase F deglycosylation of the released glycopeptides in the free solution. 26399494 0 60 theme Hydrazide 47:55 arg1 Beads 57:61 Hydrazide Beads 47:61 Hydrazide Beads 47:61 Highly Efficient Release of Glycopeptides from Hydrazide Beads by Hydroxylamine Assisted PNGase F Deglycosylation for N-Glycoproteome Analysis. 26399494 3 61 theme inherent 713:720 arg1 hindrance 729:737 the inherent steric hindrance 709:737 the inherent steric hindrance effect 709:744 However, the enzymatic release of glycopeptides captured by hydrazide beads through direct incubation of the beads with PNGase F is not efficient due to the inherent steric hindrance effect. 26399494 2 62 gly glycopeptides 500:512 arg2 glycopeptides 500:512 N-linked glycopeptides 491:512 N-linked glycopeptides 491:512 On account of the high enrichment specificity, hydrazide chemistry based solid-phase extraction of N-linked glycopeptides technique has sparked numerous interests. 26399494 1 63 theme popular 333:339 arg1 protocol 341:348 the popular protocol 329:348 the popular protocol for comprehensive glycoproteome analysis 329:389 Selective enrichment of glycopeptides from complex sample followed by cleavage of N-glycans by PNGase F to expose an easily detectable mark on the former glycosylation sites has become the popular protocol for comprehensive glycoproteome analysis. 26399494 3 64 theme hindrance 729:737 arg1 effect 739:744 the inherent steric hindrance effect 709:744 the inherent steric hindrance effect 709:744 However, the enzymatic release of glycopeptides captured by hydrazide beads through direct incubation of the beads with PNGase F is not efficient due to the inherent steric hindrance effect. 26399494 3 65 theme steric 722:727 arg1 hindrance 729:737 the inherent steric hindrance 709:737 the inherent steric hindrance effect 709:744 However, the enzymatic release of glycopeptides captured by hydrazide beads through direct incubation of the beads with PNGase F is not efficient due to the inherent steric hindrance effect. 26399494 3 66 theme PNGase 676:681 arg1 F 683:683 PNGase F 676:683 PNGase F 676:683 However, the enzymatic release of glycopeptides captured by hydrazide beads through direct incubation of the beads with PNGase F is not efficient due to the inherent steric hindrance effect. 26399494 1 67 gly glycosylation 298:310 arg2 sites 312:316 the former glycosylation sites 287:316 the former glycosylation sites 287:316 Selective enrichment of glycopeptides from complex sample followed by cleavage of N-glycans by PNGase F to expose an easily detectable mark on the former glycosylation sites has become the popular protocol for comprehensive glycoproteome analysis. 26399494 1 68 theme Selective 144:152 arg1 enrichment 154:163 Selective enrichment 144:163 Selective enrichment of glycopeptides from complex sample followed by cleavage of N-glycans by PNGase F to expose an easily detectable mark on the former glycosylation sites 144:316 Selective enrichment of glycopeptides from complex sample followed by cleavage of N-glycans by PNGase F to expose an easily detectable mark on the former glycosylation sites has become the popular protocol for comprehensive glycoproteome analysis. 26399494 6 69 gly N-glycosylation 1248:1262 arg2 sites 1264:1268 27% more N-glycosylation sites 1239:1268 27% more N-glycosylation sites 1239:1268 It was found that 27% more N-glycosylation sites were identified by the HAPD strategy compared with the conventional method. 26399494 4 70 from glycopeptides 1037:1049 arg1 solution 1063:1070 the free solution 1054:1070 the free solution 1054:1070 In this study, we developed a hydroxylamine assisted PNGase F deglycosylation (HAPD) method using the hydroxylamine to release glycopeptides captured on the hydrazide beads through the cleavage of hydrazone bonds by transamination followed with the PNGase F deglycosylation of the released glycopeptides in the free solution. 26399494 4 71 theme deglycosylation 809:823 arg1 method 832:837 a hydroxylamine assisted PNGase F deglycosylation (HAPD) method 775:837 a hydroxylamine assisted PNGase F deglycosylation (HAPD) method using the hydroxylamine to release glycopeptides captured on the hydrazide beads through the cleavage of hydrazone bonds by transamination followed with the PNGase F deglycosylation of the released glycopeptides in the free solution 775:1070 In this study, we developed a hydroxylamine assisted PNGase F deglycosylation (HAPD) method using the hydroxylamine to release glycopeptides captured on the hydrazide beads through the cleavage of hydrazone bonds by transamination followed with the PNGase F deglycosylation of the released glycopeptides in the free solution. 26399494 4 72 theme F 807:807 arg1 method 832:837 a hydroxylamine assisted PNGase F deglycosylation (HAPD) method 775:837 a hydroxylamine assisted PNGase F deglycosylation (HAPD) method using the hydroxylamine to release glycopeptides captured on the hydrazide beads through the cleavage of hydrazone bonds by transamination followed with the PNGase F deglycosylation of the released glycopeptides in the free solution 775:1070 In this study, we developed a hydroxylamine assisted PNGase F deglycosylation (HAPD) method using the hydroxylamine to release glycopeptides captured on the hydrazide beads through the cleavage of hydrazone bonds by transamination followed with the PNGase F deglycosylation of the released glycopeptides in the free solution. 26399494 4 73 theme hydroxylamine 777:789 arg1 method 832:837 a hydroxylamine assisted PNGase F deglycosylation (HAPD) method 775:837 a hydroxylamine assisted PNGase F deglycosylation (HAPD) method using the hydroxylamine to release glycopeptides captured on the hydrazide beads through the cleavage of hydrazone bonds by transamination followed with the PNGase F deglycosylation of the released glycopeptides in the free solution 775:1070 In this study, we developed a hydroxylamine assisted PNGase F deglycosylation (HAPD) method using the hydroxylamine to release glycopeptides captured on the hydrazide beads through the cleavage of hydrazone bonds by transamination followed with the PNGase F deglycosylation of the released glycopeptides in the free solution. 26399494 3 74 gly glycopeptides 590:602 arg2 glycopeptides 590:602 glycopeptides 590:602 glycopeptides captured by hydrazide beads 590:630 However, the enzymatic release of glycopeptides captured by hydrazide beads through direct incubation of the beads with PNGase F is not efficient due to the inherent steric hindrance effect. 26399494 0 75 theme Hydroxylamine 66:78 arg1 Deglycosylation 98:112 Hydroxylamine Assisted PNGase F Deglycosylation 66:112 Hydroxylamine Assisted PNGase F Deglycosylation for N-Glycoproteome Analysis 66:141 Highly Efficient Release of Glycopeptides from Hydrazide Beads by Hydroxylamine Assisted PNGase F Deglycosylation for N-Glycoproteome Analysis. 26399494 1 76 dep detectable 268:277 arg1 mark 279:282 mark 279:282 mark on the former glycosylation sites 279:316 Selective enrichment of glycopeptides from complex sample followed by cleavage of N-glycans by PNGase F to expose an easily detectable mark on the former glycosylation sites has become the popular protocol for comprehensive glycoproteome analysis. 26399494 3 77 theme beads 665:669 arg1 incubation 647:656 direct incubation 640:656 direct incubation of the beads with PNGase F 640:683 However, the enzymatic release of glycopeptides captured by hydrazide beads through direct incubation of the beads with PNGase F is not efficient due to the inherent steric hindrance effect. 26399494 4 78 gly glycopeptides 874:886 arg2 glycopeptides 874:886 the hydroxylamine to release glycopeptides 845:886 the hydroxylamine to release glycopeptides captured on the hydrazide beads through the cleavage of hydrazone bonds by transamination followed with the PNGase F deglycosylation of the released glycopeptides in the free solution 845:1070 In this study, we developed a hydroxylamine assisted PNGase F deglycosylation (HAPD) method using the hydroxylamine to release glycopeptides captured on the hydrazide beads through the cleavage of hydrazone bonds by transamination followed with the PNGase F deglycosylation of the released glycopeptides in the free solution. 26399494 7 79 theme peptides 1404:1411 arg1 ratio 1360:1364 the ratio 1356:1364 the ratio of identified N-terminal glycosylated peptides 1356:1411 Moreover, the ratio of identified N-terminal glycosylated peptides was improved over 5-fold. 26399494 4 80 theme glycopeptides 1037:1049 arg1 deglycosylation 1005:1019 the PNGase F deglycosylation 992:1019 the PNGase F deglycosylation of the released glycopeptides in the free solution 992:1070 In this study, we developed a hydroxylamine assisted PNGase F deglycosylation (HAPD) method using the hydroxylamine to release glycopeptides captured on the hydrazide beads through the cleavage of hydrazone bonds by transamination followed with the PNGase F deglycosylation of the released glycopeptides in the free solution. 26399494 4 81 dep glycopeptides 874:886 arg1 to 863:864 to 863:864 to 863:864 In this study, we developed a hydroxylamine assisted PNGase F deglycosylation (HAPD) method using the hydroxylamine to release glycopeptides captured on the hydrazide beads through the cleavage of hydrazone bonds by transamination followed with the PNGase F deglycosylation of the released glycopeptides in the free solution. 26399494 1 82 from sample 195:200 arg1 enrichment 154:163 Selective enrichment 144:163 Selective enrichment of glycopeptides from complex sample followed by cleavage of N-glycans by PNGase F to expose an easily detectable mark on the former glycosylation sites 144:316 Selective enrichment of glycopeptides from complex sample followed by cleavage of N-glycans by PNGase F to expose an easily detectable mark on the former glycosylation sites has become the popular protocol for comprehensive glycoproteome analysis. 26399494 1 83 theme glycopeptides 168:180 arg1 enrichment 154:163 Selective enrichment 144:163 Selective enrichment of glycopeptides from complex sample followed by cleavage of N-glycans by PNGase F to expose an easily detectable mark on the former glycosylation sites 144:316 Selective enrichment of glycopeptides from complex sample followed by cleavage of N-glycans by PNGase F to expose an easily detectable mark on the former glycosylation sites has become the popular protocol for comprehensive glycoproteome analysis. 26399494 3 84 with incubation 647:656 arg1 F 683:683 PNGase F 676:683 PNGase F 676:683 However, the enzymatic release of glycopeptides captured by hydrazide beads through direct incubation of the beads with PNGase F is not efficient due to the inherent steric hindrance effect. 26322290 8 0 from positions 1049:1057 arg1 sites 1029:1033 three additional N-glycosylation sites 996:1033 three additional N-glycosylation sites at amino-acid positions 30, 34 and 86 996:1071 RESULTS In the new modified analog, three additional N-glycosylation sites at amino-acid positions 30, 34 and 86 were inserted. 26322290 8 0 from positions 1049:1057 arg1 analog 988:993 the new modified analog 971:993 the new modified analog 971:993 RESULTS In the new modified analog, three additional N-glycosylation sites at amino-acid positions 30, 34 and 86 were inserted. 26322290 8 1 theme additional 1002:1011 arg1 sites 1029:1033 three additional N-glycosylation sites 996:1033 three additional N-glycosylation sites at amino-acid positions 30, 34 and 86 996:1071 RESULTS In the new modified analog, three additional N-glycosylation sites at amino-acid positions 30, 34 and 86 were inserted. 26322290 8 1 theme additional 1002:1011 arg1 analog 988:993 the new modified analog 971:993 the new modified analog 971:993 RESULTS In the new modified analog, three additional N-glycosylation sites at amino-acid positions 30, 34 and 86 were inserted. 26322290 7 2 theme attached 896:903 arg1 N-carbohydrates 905:919 attached N-carbohydrates 896:919 attached N-carbohydrates 896:919 Meanwhile, 3D model of kypoetin with attached N-carbohydrates was built up using the GlyProt server. 26322290 9 3 from % 1175:1175 arg1 regions 1235:1241 the generously allowed regions 1212:1241 the generously allowed regions 1212:1241 Ramchandran plot analysis showed 81.6% of the residues in the most favored region, 15.6% in the additional allowed, 1.4% in the generously allowed regions and 1.4% in the disallowed region. 26322290 9 3 from % 1175:1175 arg1 region 1163:1168 the most favored region 1146:1168 the most favored region 1146:1168 Ramchandran plot analysis showed 81.6% of the residues in the most favored region, 15.6% in the additional allowed, 1.4% in the generously allowed regions and 1.4% in the disallowed region. 26322290 9 3 from % 1175:1175 arg1 additional 1184:1193 additional 1184:1193 additional 1184:1193 Ramchandran plot analysis showed 81.6% of the residues in the most favored region, 15.6% in the additional allowed, 1.4% in the generously allowed regions and 1.4% in the disallowed region. 26322290 9 3 from % 1175:1175 arg1 region 1270:1275 the disallowed region 1255:1275 the disallowed region 1255:1275 Ramchandran plot analysis showed 81.6% of the residues in the most favored region, 15.6% in the additional allowed, 1.4% in the generously allowed regions and 1.4% in the disallowed region. 26322290 11 4 theme surface 1402:1408 arg1 higher 1444:1449 higher 1444:1449 higher 1444:1449 The whole solvent accessible surface areas of kypoetin (15132.69) were higher than EPO (9938.62). 26322290 11 4 theme surface 1402:1408 arg1 areas 1410:1414 The whole solvent accessible surface areas 1373:1414 The whole solvent accessible surface areas of kypoetin (15132.69) 1373:1437 The whole solvent accessible surface areas of kypoetin (15132.69) were higher than EPO (9938.62). 26322290 7 5 theme kypoetin 882:889 arg1 model 873:877 3D model 870:877 3D model of kypoetin with attached N-carbohydrates 870:919 Meanwhile, 3D model of kypoetin with attached N-carbohydrates was built up using the GlyProt server. 26322290 7 5 theme kypoetin 882:889 arg1 Meanwhile 859:867 Meanwhile 859:867 Meanwhile 859:867 Meanwhile, 3D model of kypoetin with attached N-carbohydrates was built up using the GlyProt server. 26322290 6 6 used used 820:823 arg2 plot 781:784 Ramchandran plot 769:784 Ramchandran plot obtained from PROCHECK server 769:814 Ramchandran plot obtained from PROCHECK server was used to check stereochemical property. 26322290 8 7 theme amino-acid 1038:1047 arg1 positions 1049:1057 amino-acid positions 30, 34 and 86 1038:1071 amino-acid positions 30, 34 and 86 1038:1071 RESULTS In the new modified analog, three additional N-glycosylation sites at amino-acid positions 30, 34 and 86 were inserted. 26322290 8 8 gly N-glycosylation 1013:1027 arg2 three 996:1000 three 996:1000 three 996:1000 RESULTS In the new modified analog, three additional N-glycosylation sites at amino-acid positions 30, 34 and 86 were inserted. 26322290 8 8 gly N-glycosylation 1013:1027 arg2 positions 1049:1057 amino-acid positions 30, 34 and 86 1038:1071 amino-acid positions 30, 34 and 86 1038:1071 RESULTS In the new modified analog, three additional N-glycosylation sites at amino-acid positions 30, 34 and 86 were inserted. 26322290 8 8 gly N-glycosylation 1013:1027 arg2 analog 988:993 the new modified analog 971:993 the new modified analog 971:993 RESULTS In the new modified analog, three additional N-glycosylation sites at amino-acid positions 30, 34 and 86 were inserted. 26322290 8 8 gly N-glycosylation 1013:1027 arg2 sites 1029:1033 three additional N-glycosylation sites 996:1033 three additional N-glycosylation sites at amino-acid positions 30, 34 and 86 996:1071 RESULTS In the new modified analog, three additional N-glycosylation sites at amino-acid positions 30, 34 and 86 were inserted. 26322290 5 9 theme glycoengineered 676:690 arg1 EPO 692:694 glycoengineered EPO 676:694 glycoengineered EPO 676:694 The three-dimensional model of glycoengineered EPO (named as kypoetin) was constructed using the homology modeling program. 26322290 2 10 theme new 306:308 arg1 analog 328:333 a new hyperglycosylated analog 304:333 a new hyperglycosylated analog of erythropoietin (EPO) with appropriately targeted N-linked carbohydrates 304:408 The objective of this work was to engineer a new hyperglycosylated analog of erythropoietin (EPO) with appropriately targeted N-linked carbohydrates through bioinformatics tools. 26322290 12 11 theme good 1592:1595 arg1 geometry 1597:1604 considerably good geometry 1579:1604 considerably good geometry 1579:1604 CONCLUSIONS Totally, various model evaluation methods indicated that the glycoengineered version of EPO had considerably good geometry and acceptable profiles for clinical studies and could be considered as the effective drug. 26322290 5 12 theme modeling 751:758 arg1 program 760:766 the homology modeling program 738:766 the homology modeling program 738:766 The three-dimensional model of glycoengineered EPO (named as kypoetin) was constructed using the homology modeling program. 26322290 4 13 gly N-glycosylation 552:566 arg2 sites 568:572 N-glycosylation sites 552:572 N-glycosylation sites for the target protein 552:595 Prediction of N-glycosylation sites for the target protein was done using the prediction server, NetNGlyc. 26322290 0 14 theme hyperglycosylated 39:55 arg1 analog 57:62 a new hyperglycosylated analog 33:62 a new hyperglycosylated analog of erythropoietin 33:80 In silico design and analysis of a new hyperglycosylated analog of erythropoietin to improve drug efficacy. 26322290 9 15 theme disallowed 1259:1268 arg1 region 1270:1275 the disallowed region 1255:1275 the disallowed region 1255:1275 Ramchandran plot analysis showed 81.6% of the residues in the most favored region, 15.6% in the additional allowed, 1.4% in the generously allowed regions and 1.4% in the disallowed region. 26322290 1 16 theme glycosylation 138:150 arg1 enhancement 123:133 The enhancement 119:133 The enhancement of glycosylation by applying glycoengineering approaches 119:190 BACKGROUND The enhancement of glycosylation by applying glycoengineering approaches has become widely used to boost properties for protein therapeutics. 26322290 12 17 theme glycoengineered 1544:1558 arg1 drug 1692:1695 the effective drug 1678:1695 the effective drug 1678:1695 CONCLUSIONS Totally, various model evaluation methods indicated that the glycoengineered version of EPO had considerably good geometry and acceptable profiles for clinical studies and could be considered as the effective drug. 26322290 12 17 theme glycoengineered 1544:1558 arg1 version 1560:1566 the glycoengineered version 1540:1566 the glycoengineered version of EPO 1540:1573 CONCLUSIONS Totally, various model evaluation methods indicated that the glycoengineered version of EPO had considerably good geometry and acceptable profiles for clinical studies and could be considered as the effective drug. 26322290 12 18 theme model 1500:1504 arg1 methods 1517:1523 various model evaluation methods 1492:1523 various model evaluation methods 1492:1523 CONCLUSIONS Totally, various model evaluation methods indicated that the glycoengineered version of EPO had considerably good geometry and acceptable profiles for clinical studies and could be considered as the effective drug. 26322290 9 19 theme plot 1100:1103 arg1 analysis 1105:1112 Ramchandran plot analysis 1088:1112 Ramchandran plot analysis 1088:1112 Ramchandran plot analysis showed 81.6% of the residues in the most favored region, 15.6% in the additional allowed, 1.4% in the generously allowed regions and 1.4% in the disallowed region. 26322290 0 20 theme drug 93:96 arg1 efficacy 98:105 drug efficacy 93:105 drug efficacy 93:105 In silico design and analysis of a new hyperglycosylated analog of erythropoietin to improve drug efficacy. 26322290 2 21 theme N-linked 387:394 arg1 carbohydrates 396:408 appropriately targeted N-linked carbohydrates 364:408 appropriately targeted N-linked carbohydrates 364:408 The objective of this work was to engineer a new hyperglycosylated analog of erythropoietin (EPO) with appropriately targeted N-linked carbohydrates through bioinformatics tools. 26322290 0 22 theme In 0:1 arg1 design 10:15 In silico design 0:15 In silico design 0:15 In silico design and analysis of a new hyperglycosylated analog of erythropoietin to improve drug efficacy. 26322290 8 23 from RESULTS 960:966 arg1 sites 1029:1033 three additional N-glycosylation sites 996:1033 three additional N-glycosylation sites at amino-acid positions 30, 34 and 86 996:1071 RESULTS In the new modified analog, three additional N-glycosylation sites at amino-acid positions 30, 34 and 86 were inserted. 26322290 8 23 from RESULTS 960:966 arg1 analog 988:993 the new modified analog 971:993 the new modified analog 971:993 RESULTS In the new modified analog, three additional N-glycosylation sites at amino-acid positions 30, 34 and 86 were inserted. 26322290 4 24 theme target 582:587 arg1 protein 589:595 the target protein 578:595 the target protein 578:595 Prediction of N-glycosylation sites for the target protein was done using the prediction server, NetNGlyc. 26322290 9 25 from residues 1134:1141 arg1 region 1163:1168 the most favored region 1146:1168 the most favored region 1146:1168 Ramchandran plot analysis showed 81.6% of the residues in the most favored region, 15.6% in the additional allowed, 1.4% in the generously allowed regions and 1.4% in the disallowed region. 26322290 10 26 theme structural 1281:1290 arg1 modeling 1292:1299 3D structural modeling 1278:1299 3D structural modeling 1278:1299 3D structural modeling showed that attached carbohydrates were on the proper spatial position. 26322290 3 27 theme protein 470:476 arg1 sequence 478:485 The EPO protein sequence 462:485 The EPO protein sequence 462:485 MATERIALS AND METHODS The EPO protein sequence was retrieved from NCBI protein sequence database. 26322290 12 28 theme various 1492:1498 arg1 methods 1517:1523 various model evaluation methods 1492:1523 various model evaluation methods 1492:1523 CONCLUSIONS Totally, various model evaluation methods indicated that the glycoengineered version of EPO had considerably good geometry and acceptable profiles for clinical studies and could be considered as the effective drug. 26322290 4 29 theme N-glycosylation 552:566 arg1 sites 568:572 N-glycosylation sites 552:572 N-glycosylation sites for the target protein 552:595 Prediction of N-glycosylation sites for the target protein was done using the prediction server, NetNGlyc. 26322290 6 30 theme PROCHECK 800:807 arg1 server 809:814 PROCHECK server 800:814 PROCHECK server 800:814 Ramchandran plot obtained from PROCHECK server was used to check stereochemical property. 26322290 3 31 theme protein 511:517 arg1 database 528:535 NCBI protein sequence database 506:535 NCBI protein sequence database 506:535 MATERIALS AND METHODS The EPO protein sequence was retrieved from NCBI protein sequence database. 26322290 7 32 with kypoetin 882:889 arg1 N-carbohydrates 905:919 attached N-carbohydrates 896:919 attached N-carbohydrates 896:919 Meanwhile, 3D model of kypoetin with attached N-carbohydrates was built up using the GlyProt server. 26322290 8 33 theme new 975:977 arg1 sites 1029:1033 three additional N-glycosylation sites 996:1033 three additional N-glycosylation sites at amino-acid positions 30, 34 and 86 996:1071 RESULTS In the new modified analog, three additional N-glycosylation sites at amino-acid positions 30, 34 and 86 were inserted. 26322290 8 33 theme new 975:977 arg1 analog 988:993 the new modified analog 971:993 the new modified analog 971:993 RESULTS In the new modified analog, three additional N-glycosylation sites at amino-acid positions 30, 34 and 86 were inserted. 26322290 10 34 theme attached 1313:1320 arg1 carbohydrates 1322:1334 attached carbohydrates 1313:1334 attached carbohydrates 1313:1334 3D structural modeling showed that attached carbohydrates were on the proper spatial position. 26322290 10 35 theme spatial 1355:1361 arg1 position 1363:1370 the proper spatial position 1344:1370 the proper spatial position 1344:1370 3D structural modeling showed that attached carbohydrates were on the proper spatial position. 26322290 7 36 theme GlyProt 944:950 arg1 server 952:957 the GlyProt server 940:957 the GlyProt server 940:957 Meanwhile, 3D model of kypoetin with attached N-carbohydrates was built up using the GlyProt server. 26322290 1 37 theme protein 239:245 arg1 therapeutics 247:258 protein therapeutics 239:258 protein therapeutics 239:258 BACKGROUND The enhancement of glycosylation by applying glycoengineering approaches has become widely used to boost properties for protein therapeutics. 26322290 0 38 dep In 0:1 arg1 silico 3:8 silico 3:8 silico 3:8 In silico design and analysis of a new hyperglycosylated analog of erythropoietin to improve drug efficacy. 26322290 5 39 theme EPO 692:694 arg1 model 667:671 The three-dimensional model 645:671 The three-dimensional model of glycoengineered EPO (named as kypoetin) 645:714 The three-dimensional model of glycoengineered EPO (named as kypoetin) was constructed using the homology modeling program. 26322290 9 40 from % 1250:1250 arg1 regions 1235:1241 the generously allowed regions 1212:1241 the generously allowed regions 1212:1241 Ramchandran plot analysis showed 81.6% of the residues in the most favored region, 15.6% in the additional allowed, 1.4% in the generously allowed regions and 1.4% in the disallowed region. 26322290 9 40 from % 1250:1250 arg1 region 1163:1168 the most favored region 1146:1168 the most favored region 1146:1168 Ramchandran plot analysis showed 81.6% of the residues in the most favored region, 15.6% in the additional allowed, 1.4% in the generously allowed regions and 1.4% in the disallowed region. 26322290 9 40 from % 1250:1250 arg1 region 1270:1275 the disallowed region 1255:1275 the disallowed region 1255:1275 Ramchandran plot analysis showed 81.6% of the residues in the most favored region, 15.6% in the additional allowed, 1.4% in the generously allowed regions and 1.4% in the disallowed region. 26322290 9 40 from % 1250:1250 arg1 additional 1184:1193 additional 1184:1193 additional 1184:1193 Ramchandran plot analysis showed 81.6% of the residues in the most favored region, 15.6% in the additional allowed, 1.4% in the generously allowed regions and 1.4% in the disallowed region. 26322290 8 41 theme N-glycosylation 1013:1027 arg1 sites 1029:1033 three additional N-glycosylation sites 996:1033 three additional N-glycosylation sites at amino-acid positions 30, 34 and 86 996:1071 RESULTS In the new modified analog, three additional N-glycosylation sites at amino-acid positions 30, 34 and 86 were inserted. 26322290 8 41 theme N-glycosylation 1013:1027 arg1 analog 988:993 the new modified analog 971:993 the new modified analog 971:993 RESULTS In the new modified analog, three additional N-glycosylation sites at amino-acid positions 30, 34 and 86 were inserted. 26322290 4 42 theme prediction 616:625 arg1 NetNGlyc 635:642 NetNGlyc 635:642 NetNGlyc 635:642 Prediction of N-glycosylation sites for the target protein was done using the prediction server, NetNGlyc. 26322290 4 42 theme prediction 616:625 arg1 server 627:632 the prediction server 612:632 the prediction server 612:632 Prediction of N-glycosylation sites for the target protein was done using the prediction server, NetNGlyc. 26322290 11 43 theme accessible 1391:1400 arg1 higher 1444:1449 higher 1444:1449 higher 1444:1449 The whole solvent accessible surface areas of kypoetin (15132.69) were higher than EPO (9938.62). 26322290 11 43 theme accessible 1391:1400 arg1 areas 1410:1414 The whole solvent accessible surface areas 1373:1414 The whole solvent accessible surface areas of kypoetin (15132.69) 1373:1437 The whole solvent accessible surface areas of kypoetin (15132.69) were higher than EPO (9938.62). 26322290 5 44 theme three-dimensional 649:665 arg1 model 667:671 The three-dimensional model 645:671 The three-dimensional model of glycoengineered EPO (named as kypoetin) 645:714 The three-dimensional model of glycoengineered EPO (named as kypoetin) was constructed using the homology modeling program. 26322290 6 45 theme stereochemical 834:847 arg1 property 849:856 stereochemical property 834:856 stereochemical property 834:856 Ramchandran plot obtained from PROCHECK server was used to check stereochemical property. 26322290 2 46 theme work 283:286 arg1 objective 265:273 The objective 261:273 The objective of this work 261:286 The objective of this work was to engineer a new hyperglycosylated analog of erythropoietin (EPO) with appropriately targeted N-linked carbohydrates through bioinformatics tools. 26322290 1 47 theme glycoengineering 164:179 arg1 approaches 181:190 glycoengineering approaches 164:190 glycoengineering approaches 164:190 BACKGROUND The enhancement of glycosylation by applying glycoengineering approaches has become widely used to boost properties for protein therapeutics. 26322290 2 48 theme hyperglycosylated 310:326 arg1 analog 328:333 a new hyperglycosylated analog 304:333 a new hyperglycosylated analog of erythropoietin (EPO) with appropriately targeted N-linked carbohydrates 304:408 The objective of this work was to engineer a new hyperglycosylated analog of erythropoietin (EPO) with appropriately targeted N-linked carbohydrates through bioinformatics tools. 26322290 12 49 theme acceptable 1610:1619 arg1 profiles 1621:1628 acceptable profiles 1610:1628 acceptable profiles 1610:1628 CONCLUSIONS Totally, various model evaluation methods indicated that the glycoengineered version of EPO had considerably good geometry and acceptable profiles for clinical studies and could be considered as the effective drug. 26322290 9 50 from region 1163:1168 arg1 % 1207:1207 1.4% 1204:1207 1.4% in the generously allowed regions 1204:1241 Ramchandran plot analysis showed 81.6% of the residues in the most favored region, 15.6% in the additional allowed, 1.4% in the generously allowed regions and 1.4% in the disallowed region. 26322290 9 50 from region 1163:1168 arg1 % 1125:1125 81.6% 1121:1125 81.6% of the residues in the most favored region 1121:1168 Ramchandran plot analysis showed 81.6% of the residues in the most favored region, 15.6% in the additional allowed, 1.4% in the generously allowed regions and 1.4% in the disallowed region. 26322290 9 50 from region 1163:1168 arg1 % 1175:1175 15.6% 1171:1175 15.6% in the additional allowed 1171:1201 Ramchandran plot analysis showed 81.6% of the residues in the most favored region, 15.6% in the additional allowed, 1.4% in the generously allowed regions and 1.4% in the disallowed region. 26322290 9 50 from region 1163:1168 arg1 residues 1134:1141 the residues 1130:1141 the residues in the most favored region 1130:1168 Ramchandran plot analysis showed 81.6% of the residues in the most favored region, 15.6% in the additional allowed, 1.4% in the generously allowed regions and 1.4% in the disallowed region. 26322290 9 50 from region 1163:1168 arg1 % 1250:1250 1.4% 1247:1250 1.4% in the disallowed region 1247:1275 Ramchandran plot analysis showed 81.6% of the residues in the most favored region, 15.6% in the additional allowed, 1.4% in the generously allowed regions and 1.4% in the disallowed region. 26322290 2 51 theme erythropoietin 338:351 arg1 analog 328:333 a new hyperglycosylated analog 304:333 a new hyperglycosylated analog of erythropoietin (EPO) with appropriately targeted N-linked carbohydrates 304:408 The objective of this work was to engineer a new hyperglycosylated analog of erythropoietin (EPO) with appropriately targeted N-linked carbohydrates through bioinformatics tools. 26322290 5 52 theme homology 742:749 arg1 program 760:766 the homology modeling program 738:766 the homology modeling program 738:766 The three-dimensional model of glycoengineered EPO (named as kypoetin) was constructed using the homology modeling program. 26322290 9 53 theme allowed 1227:1233 arg1 regions 1235:1241 the generously allowed regions 1212:1241 the generously allowed regions 1212:1241 Ramchandran plot analysis showed 81.6% of the residues in the most favored region, 15.6% in the additional allowed, 1.4% in the generously allowed regions and 1.4% in the disallowed region. 26322290 7 54 theme 3D 870:871 arg1 model 873:877 3D model 870:877 3D model of kypoetin with attached N-carbohydrates 870:919 Meanwhile, 3D model of kypoetin with attached N-carbohydrates was built up using the GlyProt server. 26322290 7 54 theme 3D 870:871 arg1 Meanwhile 859:867 Meanwhile 859:867 Meanwhile 859:867 Meanwhile, 3D model of kypoetin with attached N-carbohydrates was built up using the GlyProt server. 26322290 12 55 theme EPO 1571:1573 arg1 drug 1692:1695 the effective drug 1678:1695 the effective drug 1678:1695 CONCLUSIONS Totally, various model evaluation methods indicated that the glycoengineered version of EPO had considerably good geometry and acceptable profiles for clinical studies and could be considered as the effective drug. 26322290 12 55 theme EPO 1571:1573 arg1 version 1560:1566 the glycoengineered version 1540:1566 the glycoengineered version of EPO 1540:1573 CONCLUSIONS Totally, various model evaluation methods indicated that the glycoengineered version of EPO had considerably good geometry and acceptable profiles for clinical studies and could be considered as the effective drug. 26322290 9 56 from % 1207:1207 arg1 regions 1235:1241 the generously allowed regions 1212:1241 the generously allowed regions 1212:1241 Ramchandran plot analysis showed 81.6% of the residues in the most favored region, 15.6% in the additional allowed, 1.4% in the generously allowed regions and 1.4% in the disallowed region. 26322290 9 56 from % 1207:1207 arg1 region 1163:1168 the most favored region 1146:1168 the most favored region 1146:1168 Ramchandran plot analysis showed 81.6% of the residues in the most favored region, 15.6% in the additional allowed, 1.4% in the generously allowed regions and 1.4% in the disallowed region. 26322290 9 56 from % 1207:1207 arg1 region 1270:1275 the disallowed region 1255:1275 the disallowed region 1255:1275 Ramchandran plot analysis showed 81.6% of the residues in the most favored region, 15.6% in the additional allowed, 1.4% in the generously allowed regions and 1.4% in the disallowed region. 26322290 9 56 from % 1207:1207 arg1 additional 1184:1193 additional 1184:1193 additional 1184:1193 Ramchandran plot analysis showed 81.6% of the residues in the most favored region, 15.6% in the additional allowed, 1.4% in the generously allowed regions and 1.4% in the disallowed region. 26322290 0 57 theme analog 57:62 arg1 design 10:15 In silico design 0:15 In silico design 0:15 In silico design and analysis of a new hyperglycosylated analog of erythropoietin to improve drug efficacy. 26322290 0 57 theme analog 57:62 arg1 analysis 21:28 analysis 21:28 analysis 21:28 In silico design and analysis of a new hyperglycosylated analog of erythropoietin to improve drug efficacy. 26322290 0 58 theme erythropoietin 67:80 arg1 analog 57:62 a new hyperglycosylated analog 33:62 a new hyperglycosylated analog of erythropoietin 33:80 In silico design and analysis of a new hyperglycosylated analog of erythropoietin to improve drug efficacy. 26322290 12 59 theme evaluation 1506:1515 arg1 methods 1517:1523 various model evaluation methods 1492:1523 various model evaluation methods 1492:1523 CONCLUSIONS Totally, various model evaluation methods indicated that the glycoengineered version of EPO had considerably good geometry and acceptable profiles for clinical studies and could be considered as the effective drug. 26322290 9 60 theme Ramchandran 1088:1098 arg1 analysis 1105:1112 Ramchandran plot analysis 1088:1112 Ramchandran plot analysis 1088:1112 Ramchandran plot analysis showed 81.6% of the residues in the most favored region, 15.6% in the additional allowed, 1.4% in the generously allowed regions and 1.4% in the disallowed region. 26322290 0 61 gly hyperglycosylated 39:55 arg1 analog 57:62 a new hyperglycosylated analog 33:62 a new hyperglycosylated analog of erythropoietin 33:80 In silico design and analysis of a new hyperglycosylated analog of erythropoietin to improve drug efficacy. 26322290 12 62 theme effective 1682:1690 arg1 drug 1692:1695 the effective drug 1678:1695 the effective drug 1678:1695 CONCLUSIONS Totally, various model evaluation methods indicated that the glycoengineered version of EPO had considerably good geometry and acceptable profiles for clinical studies and could be considered as the effective drug. 26322290 12 62 theme effective 1682:1690 arg1 version 1560:1566 the glycoengineered version 1540:1566 the glycoengineered version of EPO 1540:1573 CONCLUSIONS Totally, various model evaluation methods indicated that the glycoengineered version of EPO had considerably good geometry and acceptable profiles for clinical studies and could be considered as the effective drug. 26322290 10 63 theme 3D 1278:1279 arg1 modeling 1292:1299 3D structural modeling 1278:1299 3D structural modeling 1278:1299 3D structural modeling showed that attached carbohydrates were on the proper spatial position. 26322290 12 64 dep CONCLUSIONS 1471:1481 arg1 indicated 1525:1533 indicated 1525:1533 indicated that the glycoengineered version of EPO had considerably good geometry and acceptable profiles for clinical studies and could be considered as the effective drug 1525:1695 CONCLUSIONS Totally, various model evaluation methods indicated that the glycoengineered version of EPO had considerably good geometry and acceptable profiles for clinical studies and could be considered as the effective drug. 26322290 1 65 dep BACKGROUND 108:117 arg1 become 196:201 become 196:201 has become widely used to boost properties for protein therapeutics 192:258 BACKGROUND The enhancement of glycosylation by applying glycoengineering approaches has become widely used to boost properties for protein therapeutics. 26322290 11 66 theme kypoetin 1419:1426 arg1 higher 1444:1449 higher 1444:1449 higher 1444:1449 The whole solvent accessible surface areas of kypoetin (15132.69) were higher than EPO (9938.62). 26322290 11 66 theme kypoetin 1419:1426 arg1 areas 1410:1414 The whole solvent accessible surface areas 1373:1414 The whole solvent accessible surface areas of kypoetin (15132.69) 1373:1437 The whole solvent accessible surface areas of kypoetin (15132.69) were higher than EPO (9938.62). 26322290 3 67 theme EPO 466:468 arg1 sequence 478:485 The EPO protein sequence 462:485 The EPO protein sequence 462:485 MATERIALS AND METHODS The EPO protein sequence was retrieved from NCBI protein sequence database. 26322290 3 68 dep MATERIALS 440:448 arg1 sequence 478:485 The EPO protein sequence 462:485 The EPO protein sequence 462:485 MATERIALS AND METHODS The EPO protein sequence was retrieved from NCBI protein sequence database. 26322290 2 69 theme targeted 378:385 arg1 carbohydrates 396:408 appropriately targeted N-linked carbohydrates 364:408 appropriately targeted N-linked carbohydrates 364:408 The objective of this work was to engineer a new hyperglycosylated analog of erythropoietin (EPO) with appropriately targeted N-linked carbohydrates through bioinformatics tools. 26322290 6 70 theme Ramchandran 769:779 arg1 plot 781:784 Ramchandran plot 769:784 Ramchandran plot obtained from PROCHECK server 769:814 Ramchandran plot obtained from PROCHECK server was used to check stereochemical property. 26322290 2 71 link N-linked 387:394 arg1 carbohydrates 396:408 appropriately targeted N-linked carbohydrates 364:408 appropriately targeted N-linked carbohydrates 364:408 The objective of this work was to engineer a new hyperglycosylated analog of erythropoietin (EPO) with appropriately targeted N-linked carbohydrates through bioinformatics tools. 26322290 9 72 theme residues 1134:1141 arg1 % 1207:1207 1.4% 1204:1207 1.4% in the generously allowed regions 1204:1241 Ramchandran plot analysis showed 81.6% of the residues in the most favored region, 15.6% in the additional allowed, 1.4% in the generously allowed regions and 1.4% in the disallowed region. 26322290 9 72 theme residues 1134:1141 arg1 % 1125:1125 81.6% 1121:1125 81.6% of the residues in the most favored region 1121:1168 Ramchandran plot analysis showed 81.6% of the residues in the most favored region, 15.6% in the additional allowed, 1.4% in the generously allowed regions and 1.4% in the disallowed region. 26322290 9 72 theme residues 1134:1141 arg1 % 1175:1175 15.6% 1171:1175 15.6% in the additional allowed 1171:1201 Ramchandran plot analysis showed 81.6% of the residues in the most favored region, 15.6% in the additional allowed, 1.4% in the generously allowed regions and 1.4% in the disallowed region. 26322290 9 72 theme residues 1134:1141 arg1 residues 1134:1141 the residues 1130:1141 the residues in the most favored region 1130:1168 Ramchandran plot analysis showed 81.6% of the residues in the most favored region, 15.6% in the additional allowed, 1.4% in the generously allowed regions and 1.4% in the disallowed region. 26322290 9 72 theme residues 1134:1141 arg1 % 1250:1250 1.4% 1247:1250 1.4% in the disallowed region 1247:1275 Ramchandran plot analysis showed 81.6% of the residues in the most favored region, 15.6% in the additional allowed, 1.4% in the generously allowed regions and 1.4% in the disallowed region. 26322290 2 73 with analog 328:333 arg1 carbohydrates 396:408 appropriately targeted N-linked carbohydrates 364:408 appropriately targeted N-linked carbohydrates 364:408 The objective of this work was to engineer a new hyperglycosylated analog of erythropoietin (EPO) with appropriately targeted N-linked carbohydrates through bioinformatics tools. 26322290 12 74 theme clinical 1634:1641 arg1 studies 1643:1649 clinical studies 1634:1649 clinical studies 1634:1649 CONCLUSIONS Totally, various model evaluation methods indicated that the glycoengineered version of EPO had considerably good geometry and acceptable profiles for clinical studies and could be considered as the effective drug. 26322290 4 75 theme sites 568:572 arg1 Prediction 538:547 Prediction 538:547 Prediction of N-glycosylation sites for the target protein 538:595 Prediction of N-glycosylation sites for the target protein was done using the prediction server, NetNGlyc. 26322290 12 76 contain had 1575:1577 arg2 profiles 1621:1628 acceptable profiles 1610:1628 acceptable profiles 1610:1628 CONCLUSIONS Totally, various model evaluation methods indicated that the glycoengineered version of EPO had considerably good geometry and acceptable profiles for clinical studies and could be considered as the effective drug. 26322290 12 76 contain had 1575:1577 arg2 geometry 1597:1604 considerably good geometry 1579:1604 considerably good geometry 1579:1604 CONCLUSIONS Totally, various model evaluation methods indicated that the glycoengineered version of EPO had considerably good geometry and acceptable profiles for clinical studies and could be considered as the effective drug. 26322290 12 76 contain had 1575:1577 arg1 drug 1692:1695 the effective drug 1678:1695 the effective drug 1678:1695 CONCLUSIONS Totally, various model evaluation methods indicated that the glycoengineered version of EPO had considerably good geometry and acceptable profiles for clinical studies and could be considered as the effective drug. 26322290 12 76 contain had 1575:1577 arg1 version 1560:1566 the glycoengineered version 1540:1566 the glycoengineered version of EPO 1540:1573 CONCLUSIONS Totally, various model evaluation methods indicated that the glycoengineered version of EPO had considerably good geometry and acceptable profiles for clinical studies and could be considered as the effective drug. 26322290 2 77 theme bioinformatics 418:431 arg1 tools 433:437 bioinformatics tools 418:437 bioinformatics tools 418:437 The objective of this work was to engineer a new hyperglycosylated analog of erythropoietin (EPO) with appropriately targeted N-linked carbohydrates through bioinformatics tools. 26322290 0 78 theme new 35:37 arg1 analog 57:62 a new hyperglycosylated analog 33:62 a new hyperglycosylated analog of erythropoietin 33:80 In silico design and analysis of a new hyperglycosylated analog of erythropoietin to improve drug efficacy. 26322290 9 79 theme favored 1155:1161 arg1 region 1163:1168 the most favored region 1146:1168 the most favored region 1146:1168 Ramchandran plot analysis showed 81.6% of the residues in the most favored region, 15.6% in the additional allowed, 1.4% in the generously allowed regions and 1.4% in the disallowed region. 26322290 3 80 theme sequence 519:526 arg1 database 528:535 NCBI protein sequence database 506:535 NCBI protein sequence database 506:535 MATERIALS AND METHODS The EPO protein sequence was retrieved from NCBI protein sequence database. 26322290 9 81 from % 1125:1125 arg1 regions 1235:1241 the generously allowed regions 1212:1241 the generously allowed regions 1212:1241 Ramchandran plot analysis showed 81.6% of the residues in the most favored region, 15.6% in the additional allowed, 1.4% in the generously allowed regions and 1.4% in the disallowed region. 26322290 9 81 from % 1125:1125 arg1 region 1163:1168 the most favored region 1146:1168 the most favored region 1146:1168 Ramchandran plot analysis showed 81.6% of the residues in the most favored region, 15.6% in the additional allowed, 1.4% in the generously allowed regions and 1.4% in the disallowed region. 26322290 9 81 from % 1125:1125 arg1 region 1270:1275 the disallowed region 1255:1275 the disallowed region 1255:1275 Ramchandran plot analysis showed 81.6% of the residues in the most favored region, 15.6% in the additional allowed, 1.4% in the generously allowed regions and 1.4% in the disallowed region. 26322290 9 81 from % 1125:1125 arg1 additional 1184:1193 additional 1184:1193 additional 1184:1193 Ramchandran plot analysis showed 81.6% of the residues in the most favored region, 15.6% in the additional allowed, 1.4% in the generously allowed regions and 1.4% in the disallowed region. 26322290 3 82 theme NCBI 506:509 arg1 database 528:535 NCBI protein sequence database 506:535 NCBI protein sequence database 506:535 MATERIALS AND METHODS The EPO protein sequence was retrieved from NCBI protein sequence database. 26322290 8 83 dep positions 1049:1057 arg1 86 1070:1071 86 1070:1071 86 1070:1071 RESULTS In the new modified analog, three additional N-glycosylation sites at amino-acid positions 30, 34 and 86 were inserted. 26322290 8 83 dep positions 1049:1057 arg1 34 1063:1064 34 1063:1064 34 1063:1064 RESULTS In the new modified analog, three additional N-glycosylation sites at amino-acid positions 30, 34 and 86 were inserted. 26322290 8 83 dep positions 1049:1057 arg1 30 1059:1060 30 1059:1060 30 1059:1060 RESULTS In the new modified analog, three additional N-glycosylation sites at amino-acid positions 30, 34 and 86 were inserted. 26322290 8 84 theme modified 979:986 arg1 sites 1029:1033 three additional N-glycosylation sites 996:1033 three additional N-glycosylation sites at amino-acid positions 30, 34 and 86 996:1071 RESULTS In the new modified analog, three additional N-glycosylation sites at amino-acid positions 30, 34 and 86 were inserted. 26322290 8 84 theme modified 979:986 arg1 analog 988:993 the new modified analog 971:993 the new modified analog 971:993 RESULTS In the new modified analog, three additional N-glycosylation sites at amino-acid positions 30, 34 and 86 were inserted. 26322290 2 85 gly hyperglycosylated 310:326 arg1 analog 328:333 a new hyperglycosylated analog 304:333 a new hyperglycosylated analog of erythropoietin (EPO) with appropriately targeted N-linked carbohydrates 304:408 The objective of this work was to engineer a new hyperglycosylated analog of erythropoietin (EPO) with appropriately targeted N-linked carbohydrates through bioinformatics tools. 26322290 10 86 theme proper 1348:1353 arg1 position 1363:1370 the proper spatial position 1344:1370 the proper spatial position 1344:1370 3D structural modeling showed that attached carbohydrates were on the proper spatial position. 26149894 0 0 theme HIV-1 106:110 arg1 Clade 112:116 HIV-1 Clade B or C 106:123 HIV-1 Clade B or C 106:123 Glycan-Dependent Neutralizing Antibodies Are Frequently Elicited in Individuals Chronically Infected with HIV-1 Clade B or C. 26149894 3 1 theme glycan 737:742 arg1 IDGC 753:756 IDGC 753:756 IDGC 753:756 We tested sera with a broad range of neutralization activity from individuals infected with HIV-1 clades B or C against panels of HIV-1 Env pseudoviruses that lacked specific glycans in the outer domain glycan cluster (ODGC) or inner domain glycan cluster (IDGC) to determine the presence of glycan-dependent neutralizing antibodies. 26149894 3 1 theme glycan 737:742 arg1 cluster 744:750 inner domain glycan cluster 724:750 inner domain glycan cluster (IDGC) 724:757 We tested sera with a broad range of neutralization activity from individuals infected with HIV-1 clades B or C against panels of HIV-1 Env pseudoviruses that lacked specific glycans in the outer domain glycan cluster (ODGC) or inner domain glycan cluster (IDGC) to determine the presence of glycan-dependent neutralizing antibodies. 26149894 3 2 theme activity 548:555 arg1 range 524:528 a broad range 516:528 a broad range of neutralization activity 516:555 We tested sera with a broad range of neutralization activity from individuals infected with HIV-1 clades B or C against panels of HIV-1 Env pseudoviruses that lacked specific glycans in the outer domain glycan cluster (ODGC) or inner domain glycan cluster (IDGC) to determine the presence of glycan-dependent neutralizing antibodies. 26149894 6 3 theme HIV-1 1470:1474 arg1 vaccines 1476:1483 candidate HIV-1 vaccines 1460:1483 candidate HIV-1 vaccines 1460:1483 Our results demonstrate that glycan-specific neutralizing antibodies arise with appreciable frequency in individuals chronically infected with HIV-1 clades B and C. Antibody responses that commonly occur during natural infection may be more feasible to induce by vaccination; thus glycan-specific neutralizing antibodies may be desirable responses to elicit with candidate HIV-1 vaccines. 26149894 5 4 located detected 989:996 arg1 sera 1001:1004 sera 1001:1004 sera that were selected for having broad, moderate, or weak neutralization potency and breadth 1001:1094 Glycan-specific neutralizing antibodies were readily detected in sera that were selected for having broad, moderate, or weak neutralization potency and breadth. 26149894 5 4 located detected 989:996 arg2 antibodies 965:974 Glycan-specific neutralizing antibodies 936:974 Glycan-specific neutralizing antibodies 936:974 Glycan-specific neutralizing antibodies were readily detected in sera that were selected for having broad, moderate, or weak neutralization potency and breadth. 26149894 1 5 theme antibodies 166:175 arg1 number 128:133 A number 126:133 A number of potent broadly neutralizing antibodies against HIV-1 126:189 A number of potent broadly neutralizing antibodies against HIV-1 have recently been identified that target epitopes on the viral envelope that contain N-linked glycans. 26149894 5 6 theme broad 1036:1040 arg1 potency 1076:1082 broad, moderate, or weak neutralization potency 1036:1082 broad, moderate, or weak neutralization potency 1036:1082 Glycan-specific neutralizing antibodies were readily detected in sera that were selected for having broad, moderate, or weak neutralization potency and breadth. 26149894 6 7 theme candidate 1460:1468 arg1 vaccines 1476:1483 candidate HIV-1 vaccines 1460:1483 candidate HIV-1 vaccines 1460:1483 Our results demonstrate that glycan-specific neutralizing antibodies arise with appreciable frequency in individuals chronically infected with HIV-1 clades B and C. Antibody responses that commonly occur during natural infection may be more feasible to induce by vaccination; thus glycan-specific neutralizing antibodies may be desirable responses to elicit with candidate HIV-1 vaccines. 26149894 3 8 theme inner 724:728 arg1 IDGC 753:756 IDGC 753:756 IDGC 753:756 We tested sera with a broad range of neutralization activity from individuals infected with HIV-1 clades B or C against panels of HIV-1 Env pseudoviruses that lacked specific glycans in the outer domain glycan cluster (ODGC) or inner domain glycan cluster (IDGC) to determine the presence of glycan-dependent neutralizing antibodies. 26149894 3 8 theme inner 724:728 arg1 cluster 744:750 inner domain glycan cluster 724:750 inner domain glycan cluster (IDGC) 724:757 We tested sera with a broad range of neutralization activity from individuals infected with HIV-1 clades B or C against panels of HIV-1 Env pseudoviruses that lacked specific glycans in the outer domain glycan cluster (ODGC) or inner domain glycan cluster (IDGC) to determine the presence of glycan-dependent neutralizing antibodies. 26149894 4 9 theme glycan 920:925 arg1 regions 927:933 these glycan regions 914:933 these glycan regions 914:933 Overall, 54% of individuals were observed to have neutralizing antibodies targeting these glycan regions. 26149894 1 10 link N-linked 277:284 arg1 glycans 286:292 N-linked glycans 277:292 N-linked glycans 277:292 A number of potent broadly neutralizing antibodies against HIV-1 have recently been identified that target epitopes on the viral envelope that contain N-linked glycans. 26149894 6 11 theme Antibody 1262:1269 arg1 responses 1271:1279 B and C. Antibody responses 1253:1279 B and C. Antibody responses that commonly occur during natural infection 1253:1324 Our results demonstrate that glycan-specific neutralizing antibodies arise with appreciable frequency in individuals chronically infected with HIV-1 clades B and C. Antibody responses that commonly occur during natural infection may be more feasible to induce by vaccination; thus glycan-specific neutralizing antibodies may be desirable responses to elicit with candidate HIV-1 vaccines. 26149894 5 12 theme moderate 1043:1050 arg1 potency 1076:1082 broad, moderate, or weak neutralization potency 1036:1082 broad, moderate, or weak neutralization potency 1036:1082 Glycan-specific neutralizing antibodies were readily detected in sera that were selected for having broad, moderate, or weak neutralization potency and breadth. 26149894 2 13 gly glycosylation 447:459 arg2 sites 461:465 particular glycosylation sites 436:465 particular glycosylation sites 436:465 It remains unknown how frequently glycan-dependent neutralizing antibodies generally arise during the course of natural infection or whether particular glycosylation sites are preferentially targeted. 26149894 3 14 from individuals 562:572 arg1 sera 506:509 sera 506:509 sera with a broad range of neutralization activity from individuals infected with HIV-1 clades B or C 506:606 We tested sera with a broad range of neutralization activity from individuals infected with HIV-1 clades B or C against panels of HIV-1 Env pseudoviruses that lacked specific glycans in the outer domain glycan cluster (ODGC) or inner domain glycan cluster (IDGC) to determine the presence of glycan-dependent neutralizing antibodies. 26149894 5 15 theme Glycan-specific 936:950 arg1 antibodies 965:974 Glycan-specific neutralizing antibodies 936:974 Glycan-specific neutralizing antibodies 936:974 Glycan-specific neutralizing antibodies were readily detected in sera that were selected for having broad, moderate, or weak neutralization potency and breadth. 26149894 1 16 theme N-linked 277:284 arg1 glycans 286:292 N-linked glycans 277:292 N-linked glycans 277:292 A number of potent broadly neutralizing antibodies against HIV-1 have recently been identified that target epitopes on the viral envelope that contain N-linked glycans. 26149894 6 17 theme neutralizing 1142:1153 arg1 antibodies 1155:1164 glycan-specific neutralizing antibodies 1126:1164 glycan-specific neutralizing antibodies 1126:1164 Our results demonstrate that glycan-specific neutralizing antibodies arise with appreciable frequency in individuals chronically infected with HIV-1 clades B and C. Antibody responses that commonly occur during natural infection may be more feasible to induce by vaccination; thus glycan-specific neutralizing antibodies may be desirable responses to elicit with candidate HIV-1 vaccines. 26149894 3 18 theme HIV-1 588:592 arg1 clades 594:599 HIV-1 clades B or C 588:606 HIV-1 clades B or C 588:606 We tested sera with a broad range of neutralization activity from individuals infected with HIV-1 clades B or C against panels of HIV-1 Env pseudoviruses that lacked specific glycans in the outer domain glycan cluster (ODGC) or inner domain glycan cluster (IDGC) to determine the presence of glycan-dependent neutralizing antibodies. 26149894 3 18 theme HIV-1 588:592 arg1 C 606:606 C 606:606 C 606:606 We tested sera with a broad range of neutralization activity from individuals infected with HIV-1 clades B or C against panels of HIV-1 Env pseudoviruses that lacked specific glycans in the outer domain glycan cluster (ODGC) or inner domain glycan cluster (IDGC) to determine the presence of glycan-dependent neutralizing antibodies. 26149894 3 18 theme HIV-1 588:592 arg1 B 601:601 B 601:601 B 601:601 We tested sera with a broad range of neutralization activity from individuals infected with HIV-1 clades B or C against panels of HIV-1 Env pseudoviruses that lacked specific glycans in the outer domain glycan cluster (ODGC) or inner domain glycan cluster (IDGC) to determine the presence of glycan-dependent neutralizing antibodies. 26149894 6 19 theme glycan-specific 1126:1140 arg1 antibodies 1155:1164 glycan-specific neutralizing antibodies 1126:1164 glycan-specific neutralizing antibodies 1126:1164 Our results demonstrate that glycan-specific neutralizing antibodies arise with appreciable frequency in individuals chronically infected with HIV-1 clades B and C. Antibody responses that commonly occur during natural infection may be more feasible to induce by vaccination; thus glycan-specific neutralizing antibodies may be desirable responses to elicit with candidate HIV-1 vaccines. 26149894 0 20 theme Neutralizing 17:28 arg1 Antibodies 30:39 Glycan-Dependent Neutralizing Antibodies 0:39 Glycan-Dependent Neutralizing Antibodies 0:39 Glycan-Dependent Neutralizing Antibodies Are Frequently Elicited in Individuals Chronically Infected with HIV-1 Clade B or C. 26149894 4 21 theme neutralizing 880:891 arg1 antibodies 893:902 neutralizing antibodies 880:902 neutralizing antibodies targeting these glycan regions 880:933 Overall, 54% of individuals were observed to have neutralizing antibodies targeting these glycan regions. 26149894 6 22 from frequency 1189:1197 arg1 individuals 1202:1212 individuals 1202:1212 individuals chronically infected with HIV-1 clades 1202:1251 Our results demonstrate that glycan-specific neutralizing antibodies arise with appreciable frequency in individuals chronically infected with HIV-1 clades B and C. Antibody responses that commonly occur during natural infection may be more feasible to induce by vaccination; thus glycan-specific neutralizing antibodies may be desirable responses to elicit with candidate HIV-1 vaccines. 26149894 2 23 theme glycan-dependent 329:344 arg1 antibodies 359:368 frequently glycan-dependent neutralizing antibodies 318:368 frequently glycan-dependent neutralizing antibodies 318:368 It remains unknown how frequently glycan-dependent neutralizing antibodies generally arise during the course of natural infection or whether particular glycosylation sites are preferentially targeted. 26149894 2 24 theme infection 415:423 arg1 course 397:402 the course 393:402 the course of natural infection 393:423 It remains unknown how frequently glycan-dependent neutralizing antibodies generally arise during the course of natural infection or whether particular glycosylation sites are preferentially targeted. 26149894 0 25 theme Glycan-Dependent 0:15 arg1 Antibodies 30:39 Glycan-Dependent Neutralizing Antibodies 0:39 Glycan-Dependent Neutralizing Antibodies 0:39 Glycan-Dependent Neutralizing Antibodies Are Frequently Elicited in Individuals Chronically Infected with HIV-1 Clade B or C. 26149894 6 26 theme HIV-1 1240:1244 arg1 clades 1246:1251 HIV-1 clades 1240:1251 HIV-1 clades 1240:1251 Our results demonstrate that glycan-specific neutralizing antibodies arise with appreciable frequency in individuals chronically infected with HIV-1 clades B and C. Antibody responses that commonly occur during natural infection may be more feasible to induce by vaccination; thus glycan-specific neutralizing antibodies may be desirable responses to elicit with candidate HIV-1 vaccines. 26149894 2 27 theme natural 407:413 arg1 infection 415:423 natural infection 407:423 natural infection 407:423 It remains unknown how frequently glycan-dependent neutralizing antibodies generally arise during the course of natural infection or whether particular glycosylation sites are preferentially targeted. 26149894 4 28 theme individuals 846:856 arg1 individuals 846:856 individuals 846:856 individuals 846:856 Overall, 54% of individuals were observed to have neutralizing antibodies targeting these glycan regions. 26149894 4 28 theme individuals 846:856 arg1 % 841:841 54% 839:841 54% of individuals 839:856 Overall, 54% of individuals were observed to have neutralizing antibodies targeting these glycan regions. 26149894 1 29 dep potent 138:143 arg1 neutralizing 153:164 neutralizing 153:164 neutralizing 153:164 A number of potent broadly neutralizing antibodies against HIV-1 have recently been identified that target epitopes on the viral envelope that contain N-linked glycans. 26149894 5 30 theme weak 1056:1059 arg1 potency 1076:1082 broad, moderate, or weak neutralization potency 1036:1082 broad, moderate, or weak neutralization potency 1036:1082 Glycan-specific neutralizing antibodies were readily detected in sera that were selected for having broad, moderate, or weak neutralization potency and breadth. 26149894 3 31 with sera 506:509 arg1 range 524:528 a broad range 516:528 a broad range of neutralization activity 516:555 We tested sera with a broad range of neutralization activity from individuals infected with HIV-1 clades B or C against panels of HIV-1 Env pseudoviruses that lacked specific glycans in the outer domain glycan cluster (ODGC) or inner domain glycan cluster (IDGC) to determine the presence of glycan-dependent neutralizing antibodies. 26149894 3 32 theme domain 692:697 arg1 ODGC 715:718 ODGC 715:718 ODGC 715:718 We tested sera with a broad range of neutralization activity from individuals infected with HIV-1 clades B or C against panels of HIV-1 Env pseudoviruses that lacked specific glycans in the outer domain glycan cluster (ODGC) or inner domain glycan cluster (IDGC) to determine the presence of glycan-dependent neutralizing antibodies. 26149894 3 32 theme domain 692:697 arg1 cluster 706:712 the outer domain glycan cluster 682:712 the outer domain glycan cluster (ODGC) 682:719 We tested sera with a broad range of neutralization activity from individuals infected with HIV-1 clades B or C against panels of HIV-1 Env pseudoviruses that lacked specific glycans in the outer domain glycan cluster (ODGC) or inner domain glycan cluster (IDGC) to determine the presence of glycan-dependent neutralizing antibodies. 26149894 5 33 theme neutralizing 952:963 arg1 antibodies 965:974 Glycan-specific neutralizing antibodies 936:974 Glycan-specific neutralizing antibodies 936:974 Glycan-specific neutralizing antibodies were readily detected in sera that were selected for having broad, moderate, or weak neutralization potency and breadth. 26149894 6 34 theme appreciable 1177:1187 arg1 frequency 1189:1197 appreciable frequency 1177:1197 appreciable frequency in individuals chronically infected with HIV-1 clades 1177:1251 Our results demonstrate that glycan-specific neutralizing antibodies arise with appreciable frequency in individuals chronically infected with HIV-1 clades B and C. Antibody responses that commonly occur during natural infection may be more feasible to induce by vaccination; thus glycan-specific neutralizing antibodies may be desirable responses to elicit with candidate HIV-1 vaccines. 26149894 3 35 theme glycan 699:704 arg1 ODGC 715:718 ODGC 715:718 ODGC 715:718 We tested sera with a broad range of neutralization activity from individuals infected with HIV-1 clades B or C against panels of HIV-1 Env pseudoviruses that lacked specific glycans in the outer domain glycan cluster (ODGC) or inner domain glycan cluster (IDGC) to determine the presence of glycan-dependent neutralizing antibodies. 26149894 3 35 theme glycan 699:704 arg1 cluster 706:712 the outer domain glycan cluster 682:712 the outer domain glycan cluster (ODGC) 682:719 We tested sera with a broad range of neutralization activity from individuals infected with HIV-1 clades B or C against panels of HIV-1 Env pseudoviruses that lacked specific glycans in the outer domain glycan cluster (ODGC) or inner domain glycan cluster (IDGC) to determine the presence of glycan-dependent neutralizing antibodies. 26149894 3 36 theme pseudoviruses 636:648 arg1 panels 616:621 panels 616:621 panels of HIV-1 Env pseudoviruses that lacked specific glycans in the outer domain glycan cluster (ODGC) or inner domain glycan cluster (IDGC) to determine the presence of glycan-dependent neutralizing antibodies 616:827 We tested sera with a broad range of neutralization activity from individuals infected with HIV-1 clades B or C against panels of HIV-1 Env pseudoviruses that lacked specific glycans in the outer domain glycan cluster (ODGC) or inner domain glycan cluster (IDGC) to determine the presence of glycan-dependent neutralizing antibodies. 26149894 2 37 theme glycosylation 447:459 arg1 sites 461:465 particular glycosylation sites 436:465 particular glycosylation sites 436:465 It remains unknown how frequently glycan-dependent neutralizing antibodies generally arise during the course of natural infection or whether particular glycosylation sites are preferentially targeted. 26149894 3 38 theme neutralizing 805:816 arg1 antibodies 818:827 glycan-dependent neutralizing antibodies 788:827 glycan-dependent neutralizing antibodies 788:827 We tested sera with a broad range of neutralization activity from individuals infected with HIV-1 clades B or C against panels of HIV-1 Env pseudoviruses that lacked specific glycans in the outer domain glycan cluster (ODGC) or inner domain glycan cluster (IDGC) to determine the presence of glycan-dependent neutralizing antibodies. 26149894 5 39 theme neutralization 1061:1074 arg1 potency 1076:1082 broad, moderate, or weak neutralization potency 1036:1082 broad, moderate, or weak neutralization potency 1036:1082 Glycan-specific neutralizing antibodies were readily detected in sera that were selected for having broad, moderate, or weak neutralization potency and breadth. 26149894 2 40 theme particular 436:445 arg1 sites 461:465 particular glycosylation sites 436:465 particular glycosylation sites 436:465 It remains unknown how frequently glycan-dependent neutralizing antibodies generally arise during the course of natural infection or whether particular glycosylation sites are preferentially targeted. 26149894 3 41 theme antibodies 818:827 arg1 presence 776:783 the presence 772:783 the presence of glycan-dependent neutralizing antibodies 772:827 We tested sera with a broad range of neutralization activity from individuals infected with HIV-1 clades B or C against panels of HIV-1 Env pseudoviruses that lacked specific glycans in the outer domain glycan cluster (ODGC) or inner domain glycan cluster (IDGC) to determine the presence of glycan-dependent neutralizing antibodies. 26149894 3 42 theme outer 686:690 arg1 ODGC 715:718 ODGC 715:718 ODGC 715:718 We tested sera with a broad range of neutralization activity from individuals infected with HIV-1 clades B or C against panels of HIV-1 Env pseudoviruses that lacked specific glycans in the outer domain glycan cluster (ODGC) or inner domain glycan cluster (IDGC) to determine the presence of glycan-dependent neutralizing antibodies. 26149894 3 42 theme outer 686:690 arg1 cluster 706:712 the outer domain glycan cluster 682:712 the outer domain glycan cluster (ODGC) 682:719 We tested sera with a broad range of neutralization activity from individuals infected with HIV-1 clades B or C against panels of HIV-1 Env pseudoviruses that lacked specific glycans in the outer domain glycan cluster (ODGC) or inner domain glycan cluster (IDGC) to determine the presence of glycan-dependent neutralizing antibodies. 26149894 6 43 theme natural 1308:1314 arg1 infection 1316:1324 natural infection 1308:1324 natural infection 1308:1324 Our results demonstrate that glycan-specific neutralizing antibodies arise with appreciable frequency in individuals chronically infected with HIV-1 clades B and C. Antibody responses that commonly occur during natural infection may be more feasible to induce by vaccination; thus glycan-specific neutralizing antibodies may be desirable responses to elicit with candidate HIV-1 vaccines. 26149894 6 44 theme glycan-specific 1378:1392 arg1 antibodies 1407:1416 glycan-specific neutralizing antibodies 1378:1416 glycan-specific neutralizing antibodies 1378:1416 Our results demonstrate that glycan-specific neutralizing antibodies arise with appreciable frequency in individuals chronically infected with HIV-1 clades B and C. Antibody responses that commonly occur during natural infection may be more feasible to induce by vaccination; thus glycan-specific neutralizing antibodies may be desirable responses to elicit with candidate HIV-1 vaccines. 26149894 6 45 theme C. 1259:1260 arg1 responses 1271:1279 B and C. Antibody responses 1253:1279 B and C. Antibody responses that commonly occur during natural infection 1253:1324 Our results demonstrate that glycan-specific neutralizing antibodies arise with appreciable frequency in individuals chronically infected with HIV-1 clades B and C. Antibody responses that commonly occur during natural infection may be more feasible to induce by vaccination; thus glycan-specific neutralizing antibodies may be desirable responses to elicit with candidate HIV-1 vaccines. 26149894 6 46 theme neutralizing 1394:1405 arg1 antibodies 1407:1416 glycan-specific neutralizing antibodies 1378:1416 glycan-specific neutralizing antibodies 1378:1416 Our results demonstrate that glycan-specific neutralizing antibodies arise with appreciable frequency in individuals chronically infected with HIV-1 clades B and C. Antibody responses that commonly occur during natural infection may be more feasible to induce by vaccination; thus glycan-specific neutralizing antibodies may be desirable responses to elicit with candidate HIV-1 vaccines. 26149894 3 47 theme HIV-1 Env 626:634 arg1 pseudoviruses 636:648 HIV-1 Env pseudoviruses 626:648 HIV-1 Env pseudoviruses that lacked specific glycans in the outer domain glycan cluster (ODGC) or inner domain glycan cluster (IDGC) to determine the presence of glycan-dependent neutralizing antibodies 626:827 We tested sera with a broad range of neutralization activity from individuals infected with HIV-1 clades B or C against panels of HIV-1 Env pseudoviruses that lacked specific glycans in the outer domain glycan cluster (ODGC) or inner domain glycan cluster (IDGC) to determine the presence of glycan-dependent neutralizing antibodies. 26149894 3 48 theme neutralization 533:546 arg1 activity 548:555 neutralization activity 533:555 neutralization activity 533:555 We tested sera with a broad range of neutralization activity from individuals infected with HIV-1 clades B or C against panels of HIV-1 Env pseudoviruses that lacked specific glycans in the outer domain glycan cluster (ODGC) or inner domain glycan cluster (IDGC) to determine the presence of glycan-dependent neutralizing antibodies. 26149894 4 49 contain have 875:878 arg1 individuals 846:856 individuals 846:856 individuals 846:856 Overall, 54% of individuals were observed to have neutralizing antibodies targeting these glycan regions. 26149894 4 49 contain have 875:878 arg2 antibodies 893:902 neutralizing antibodies 880:902 neutralizing antibodies targeting these glycan regions 880:933 Overall, 54% of individuals were observed to have neutralizing antibodies targeting these glycan regions. 26149894 4 49 contain have 875:878 arg1 % 841:841 54% 839:841 54% of individuals 839:856 Overall, 54% of individuals were observed to have neutralizing antibodies targeting these glycan regions. 26149894 3 50 theme glycan-dependent 788:803 arg1 antibodies 818:827 glycan-dependent neutralizing antibodies 788:827 glycan-dependent neutralizing antibodies 788:827 We tested sera with a broad range of neutralization activity from individuals infected with HIV-1 clades B or C against panels of HIV-1 Env pseudoviruses that lacked specific glycans in the outer domain glycan cluster (ODGC) or inner domain glycan cluster (IDGC) to determine the presence of glycan-dependent neutralizing antibodies. 26149894 1 51 from epitopes 233:240 arg1 envelope 255:262 the viral envelope 245:262 the viral envelope that contain N-linked glycans 245:292 A number of potent broadly neutralizing antibodies against HIV-1 have recently been identified that target epitopes on the viral envelope that contain N-linked glycans. 26149894 3 52 theme broad 518:522 arg1 range 524:528 a broad range 516:528 a broad range of neutralization activity 516:555 We tested sera with a broad range of neutralization activity from individuals infected with HIV-1 clades B or C against panels of HIV-1 Env pseudoviruses that lacked specific glycans in the outer domain glycan cluster (ODGC) or inner domain glycan cluster (IDGC) to determine the presence of glycan-dependent neutralizing antibodies. 26149894 0 53 dep Clade 112:116 arg1 B 118:118 B 118:118 B 118:118 Glycan-Dependent Neutralizing Antibodies Are Frequently Elicited in Individuals Chronically Infected with HIV-1 Clade B or C. 26149894 0 53 dep Clade 112:116 arg1 C 123:123 C 123:123 C 123:123 Glycan-Dependent Neutralizing Antibodies Are Frequently Elicited in Individuals Chronically Infected with HIV-1 Clade B or C. 26149894 1 54 contain contain 269:275 arg2 glycans 286:292 N-linked glycans 277:292 N-linked glycans 277:292 A number of potent broadly neutralizing antibodies against HIV-1 have recently been identified that target epitopes on the viral envelope that contain N-linked glycans. 26149894 1 54 contain contain 269:275 arg1 envelope 255:262 the viral envelope 245:262 the viral envelope that contain N-linked glycans 245:292 A number of potent broadly neutralizing antibodies against HIV-1 have recently been identified that target epitopes on the viral envelope that contain N-linked glycans. 26149894 2 55 theme neutralizing 346:357 arg1 antibodies 359:368 frequently glycan-dependent neutralizing antibodies 318:368 frequently glycan-dependent neutralizing antibodies 318:368 It remains unknown how frequently glycan-dependent neutralizing antibodies generally arise during the course of natural infection or whether particular glycosylation sites are preferentially targeted. 26149894 3 56 dep clades 594:599 arg1 clades 594:599 HIV-1 clades B or C 588:606 HIV-1 clades B or C 588:606 We tested sera with a broad range of neutralization activity from individuals infected with HIV-1 clades B or C against panels of HIV-1 Env pseudoviruses that lacked specific glycans in the outer domain glycan cluster (ODGC) or inner domain glycan cluster (IDGC) to determine the presence of glycan-dependent neutralizing antibodies. 26149894 3 56 dep clades 594:599 arg1 C 606:606 C 606:606 C 606:606 We tested sera with a broad range of neutralization activity from individuals infected with HIV-1 clades B or C against panels of HIV-1 Env pseudoviruses that lacked specific glycans in the outer domain glycan cluster (ODGC) or inner domain glycan cluster (IDGC) to determine the presence of glycan-dependent neutralizing antibodies. 26149894 3 56 dep clades 594:599 arg1 B 601:601 B 601:601 B 601:601 We tested sera with a broad range of neutralization activity from individuals infected with HIV-1 clades B or C against panels of HIV-1 Env pseudoviruses that lacked specific glycans in the outer domain glycan cluster (ODGC) or inner domain glycan cluster (IDGC) to determine the presence of glycan-dependent neutralizing antibodies. 26149894 6 57 theme B 1253:1253 arg1 responses 1271:1279 B and C. Antibody responses 1253:1279 B and C. Antibody responses that commonly occur during natural infection 1253:1324 Our results demonstrate that glycan-specific neutralizing antibodies arise with appreciable frequency in individuals chronically infected with HIV-1 clades B and C. Antibody responses that commonly occur during natural infection may be more feasible to induce by vaccination; thus glycan-specific neutralizing antibodies may be desirable responses to elicit with candidate HIV-1 vaccines. 26149894 1 58 theme potent 138:143 arg1 antibodies 166:175 potent broadly neutralizing antibodies 138:175 potent broadly neutralizing antibodies against HIV-1 138:189 A number of potent broadly neutralizing antibodies against HIV-1 have recently been identified that target epitopes on the viral envelope that contain N-linked glycans. 26149894 3 59 theme domain 730:735 arg1 IDGC 753:756 IDGC 753:756 IDGC 753:756 We tested sera with a broad range of neutralization activity from individuals infected with HIV-1 clades B or C against panels of HIV-1 Env pseudoviruses that lacked specific glycans in the outer domain glycan cluster (ODGC) or inner domain glycan cluster (IDGC) to determine the presence of glycan-dependent neutralizing antibodies. 26149894 3 59 theme domain 730:735 arg1 cluster 744:750 inner domain glycan cluster 724:750 inner domain glycan cluster (IDGC) 724:757 We tested sera with a broad range of neutralization activity from individuals infected with HIV-1 clades B or C against panels of HIV-1 Env pseudoviruses that lacked specific glycans in the outer domain glycan cluster (ODGC) or inner domain glycan cluster (IDGC) to determine the presence of glycan-dependent neutralizing antibodies. 26149894 3 60 theme specific 662:669 arg1 glycans 671:677 specific glycans 662:677 specific glycans 662:677 We tested sera with a broad range of neutralization activity from individuals infected with HIV-1 clades B or C against panels of HIV-1 Env pseudoviruses that lacked specific glycans in the outer domain glycan cluster (ODGC) or inner domain glycan cluster (IDGC) to determine the presence of glycan-dependent neutralizing antibodies. 26149894 1 61 theme viral 249:253 arg1 envelope 255:262 the viral envelope 245:262 the viral envelope that contain N-linked glycans 245:292 A number of potent broadly neutralizing antibodies against HIV-1 have recently been identified that target epitopes on the viral envelope that contain N-linked glycans. 26044712 8 0 theme tallies 1068:1074 arg1 motifs 1118:1123 tallies of amino acids and N-linked glycosylation motifs 1068:1123 tallies of amino acids and N-linked glycosylation motifs 1068:1123 The tool calculates tallies of amino acids and N-linked glycosylation motifs, counts of antibody-sensitive and -resistant viruses in conjunction with each amino acid or N-glycosylation motif, and performs Fisher's exact test to detect potential positive or negative amino acid associations for the selected antibody. 26044712 6 1 theme sequence 825:832 arg1 alignments 834:843 viral protein sequence alignments 811:843 viral protein sequence alignments 811:843 The output superimposes neutralization panel data, virus epidemiological data, and viral protein sequence alignments on one page, and provides further information and analyses. 26044712 8 2 from motifs 1118:1123 arg1 conjunction 1181:1191 conjunction 1181:1191 conjunction with each amino acid 1181:1212 The tool calculates tallies of amino acids and N-linked glycosylation motifs, counts of antibody-sensitive and -resistant viruses in conjunction with each amino acid or N-glycosylation motif, and performs Fisher's exact test to detect potential positive or negative amino acid associations for the selected antibody. 26044712 8 3 theme amino 1079:1083 arg1 acids 1085:1089 amino acids 1079:1089 amino acids 1079:1089 The tool calculates tallies of amino acids and N-linked glycosylation motifs, counts of antibody-sensitive and -resistant viruses in conjunction with each amino acid or N-glycosylation motif, and performs Fisher's exact test to detect potential positive or negative amino acid associations for the selected antibody. 26044712 6 4 theme viral 811:815 arg1 alignments 834:843 viral protein sequence alignments 811:843 viral protein sequence alignments 811:843 The output superimposes neutralization panel data, virus epidemiological data, and viral protein sequence alignments on one page, and provides further information and analyses. 26044712 7 5 theme HIV 1033:1035 arg1 databases 1037:1045 the HIV databases 1029:1045 the HIV databases 1029:1045 The user can highlight alignment positions, or select antibody contact residues and view position-specific information from the HIV databases. 26044712 3 6 theme HIV 485:487 arg1 sequence 506:513 each HIV Envelope protein sequence position and each antibody 480:540 sequence 506:513 CATNAP integrates neutralization and sequence data from published studies, and allows users to analyze that data for each HIV Envelope protein sequence position and each antibody. 26044712 8 7 theme viruses 1170:1176 arg1 motifs 1118:1123 tallies of amino acids and N-linked glycosylation motifs 1068:1123 tallies of amino acids and N-linked glycosylation motifs 1068:1123 The tool calculates tallies of amino acids and N-linked glycosylation motifs, counts of antibody-sensitive and -resistant viruses in conjunction with each amino acid or N-glycosylation motif, and performs Fisher's exact test to detect potential positive or negative amino acid associations for the selected antibody. 26044712 8 7 theme viruses 1170:1176 arg1 motif 1233:1237 N-glycosylation motif 1217:1237 N-glycosylation motif 1217:1237 The tool calculates tallies of amino acids and N-linked glycosylation motifs, counts of antibody-sensitive and -resistant viruses in conjunction with each amino acid or N-glycosylation motif, and performs Fisher's exact test to detect potential positive or negative amino acid associations for the selected antibody. 26044712 8 7 theme viruses 1170:1176 arg1 counts 1126:1131 counts 1126:1131 counts of antibody-sensitive and -resistant viruses in conjunction with each amino acid 1126:1212 The tool calculates tallies of amino acids and N-linked glycosylation motifs, counts of antibody-sensitive and -resistant viruses in conjunction with each amino acid or N-glycosylation motif, and performs Fisher's exact test to detect potential positive or negative amino acid associations for the selected antibody. 26044712 3 8 from studies 429:435 arg1 data 409:412 neutralization and sequence data 381:412 data 409:412 CATNAP integrates neutralization and sequence data from published studies, and allows users to analyze that data for each HIV Envelope protein sequence position and each antibody. 26044712 8 9 theme glycosylation 1104:1116 arg1 motifs 1118:1123 tallies of amino acids and N-linked glycosylation motifs 1068:1123 tallies of amino acids and N-linked glycosylation motifs 1068:1123 The tool calculates tallies of amino acids and N-linked glycosylation motifs, counts of antibody-sensitive and -resistant viruses in conjunction with each amino acid or N-glycosylation motif, and performs Fisher's exact test to detect potential positive or negative amino acid associations for the selected antibody. 26044712 6 10 theme epidemiological 785:799 arg1 data 801:804 virus epidemiological data 779:804 virus epidemiological data 779:804 The output superimposes neutralization panel data, virus epidemiological data, and viral protein sequence alignments on one page, and provides further information and analyses. 26044712 6 11 theme protein 817:823 arg1 alignments 834:843 viral protein sequence alignments 811:843 viral protein sequence alignments 811:843 The output superimposes neutralization panel data, virus epidemiological data, and viral protein sequence alignments on one page, and provides further information and analyses. 26044712 1 12 from advances 203:210 arg1 research 241:248 HIV neutralizing antibody research 215:248 HIV neutralizing antibody research 215:248 CATNAP (Compile, Analyze and Tally NAb Panels) is a new web server at Los Alamos HIV Database, created to respond to the newest advances in HIV neutralizing antibody research. 26044712 1 13 theme web 131:133 arg1 server 135:140 new web server 127:140 a new web server at Los Alamos HIV Database 125:167 CATNAP (Compile, Analyze and Tally NAb Panels) is a new web server at Los Alamos HIV Database, created to respond to the newest advances in HIV neutralizing antibody research. 26044712 6 14 theme further 871:877 arg1 information 879:889 further information 871:889 further information 871:889 The output superimposes neutralization panel data, virus epidemiological data, and viral protein sequence alignments on one page, and provides further information and analyses. 26044712 5 15 theme specific 630:637 arg1 antibodies 639:648 specific antibodies 630:648 specific antibodies 630:648 As input, the user can pick specific antibodies and viruses, choose a panel from a published study, or supply their own data. 26044712 3 16 theme protein 498:504 arg1 sequence 506:513 each HIV Envelope protein sequence position and each antibody 480:540 sequence 506:513 CATNAP integrates neutralization and sequence data from published studies, and allows users to analyze that data for each HIV Envelope protein sequence position and each antibody. 26044712 4 17 theme analysis 584:591 arg1 options 593:599 multiple data retrieval and analysis options 556:599 options 593:599 The tool has multiple data retrieval and analysis options. 26044712 7 18 theme contact 968:974 arg1 residues 976:983 antibody contact residues 959:983 antibody contact residues 959:983 The user can highlight alignment positions, or select antibody contact residues and view position-specific information from the HIV databases. 26044712 8 19 theme N-glycosylation 1217:1231 arg1 motif 1233:1237 N-glycosylation motif 1217:1237 N-glycosylation motif 1217:1237 The tool calculates tallies of amino acids and N-linked glycosylation motifs, counts of antibody-sensitive and -resistant viruses in conjunction with each amino acid or N-glycosylation motif, and performs Fisher's exact test to detect potential positive or negative amino acid associations for the selected antibody. 26044712 3 20 theme each 528:531 arg1 antibody 533:540 each antibody 528:540 each antibody 528:540 CATNAP integrates neutralization and sequence data from published studies, and allows users to analyze that data for each HIV Envelope protein sequence position and each antibody. 26044712 9 21 theme Tally 1408:1412 arg1 Panels 1418:1423 Tally NAb Panels 1408:1423 Tally NAb Panels 1408:1423 Website name: CATNAP (Compile, Analyze and Tally NAb Panels). 26044712 1 22 dep CATNAP 75:80 arg1 Analyze 92:98 Analyze 92:98 Analyze 92:98 CATNAP (Compile, Analyze and Tally NAb Panels) is a new web server at Los Alamos HIV Database, created to respond to the newest advances in HIV neutralizing antibody research. 26044712 1 22 dep CATNAP 75:80 arg1 Compile 83:89 Compile 83:89 Compile 83:89 CATNAP (Compile, Analyze and Tally NAb Panels) is a new web server at Los Alamos HIV Database, created to respond to the newest advances in HIV neutralizing antibody research. 26044712 1 22 dep CATNAP 75:80 arg1 Panels 114:119 Tally NAb Panels 104:119 Tally NAb Panels 104:119 CATNAP (Compile, Analyze and Tally NAb Panels) is a new web server at Los Alamos HIV Database, created to respond to the newest advances in HIV neutralizing antibody research. 26044712 1 23 theme NAb 110:112 arg1 Panels 114:119 Tally NAb Panels 104:119 Tally NAb Panels 104:119 CATNAP (Compile, Analyze and Tally NAb Panels) is a new web server at Los Alamos HIV Database, created to respond to the newest advances in HIV neutralizing antibody research. 26044712 0 24 theme neutralizing 45:56 arg1 panels 67:72 neutralizing antibody panels 45:72 neutralizing antibody panels 45:72 CATNAP: a tool to compile, analyze and tally neutralizing antibody panels. 26044712 5 25 from study 695:699 arg1 panel 672:676 a panel 670:676 a panel from a published study 670:699 As input, the user can pick specific antibodies and viruses, choose a panel from a published study, or supply their own data. 26044712 3 26 theme neutralization 381:394 arg1 data 409:412 neutralization and sequence data 381:412 data 409:412 CATNAP integrates neutralization and sequence data from published studies, and allows users to analyze that data for each HIV Envelope protein sequence position and each antibody. 26044712 8 27 theme positive 1293:1300 arg1 associations 1325:1336 potential positive or negative amino acid associations 1283:1336 potential positive or negative amino acid associations for the selected antibody 1283:1362 The tool calculates tallies of amino acids and N-linked glycosylation motifs, counts of antibody-sensitive and -resistant viruses in conjunction with each amino acid or N-glycosylation motif, and performs Fisher's exact test to detect potential positive or negative amino acid associations for the selected antibody. 26044712 5 28 theme own 718:720 arg1 data 722:725 their own data 712:725 their own data 712:725 As input, the user can pick specific antibodies and viruses, choose a panel from a published study, or supply their own data. 26044712 1 29 theme newest 196:201 arg1 advances 203:210 the newest advances 192:210 the newest advances in HIV neutralizing antibody research 192:248 CATNAP (Compile, Analyze and Tally NAb Panels) is a new web server at Los Alamos HIV Database, created to respond to the newest advances in HIV neutralizing antibody research. 26044712 8 30 theme negative 1305:1312 arg1 associations 1325:1336 potential positive or negative amino acid associations 1283:1336 potential positive or negative amino acid associations for the selected antibody 1283:1362 The tool calculates tallies of amino acids and N-linked glycosylation motifs, counts of antibody-sensitive and -resistant viruses in conjunction with each amino acid or N-glycosylation motif, and performs Fisher's exact test to detect potential positive or negative amino acid associations for the selected antibody. 26044712 6 31 theme virus 779:783 arg1 data 801:804 virus epidemiological data 779:804 virus epidemiological data 779:804 The output superimposes neutralization panel data, virus epidemiological data, and viral protein sequence alignments on one page, and provides further information and analyses. 26044712 2 32 theme viral 346:350 arg1 sequences 352:360 viral sequences 346:360 viral sequences 346:360 It is a comprehensive platform focusing on neutralizing antibody potencies in conjunction with viral sequences. 26044712 8 33 theme acid 1320:1323 arg1 associations 1325:1336 potential positive or negative amino acid associations 1283:1336 potential positive or negative amino acid associations for the selected antibody 1283:1362 The tool calculates tallies of amino acids and N-linked glycosylation motifs, counts of antibody-sensitive and -resistant viruses in conjunction with each amino acid or N-glycosylation motif, and performs Fisher's exact test to detect potential positive or negative amino acid associations for the selected antibody. 26044712 3 34 theme sequence 400:407 arg1 data 409:412 neutralization and sequence data 381:412 data 409:412 CATNAP integrates neutralization and sequence data from published studies, and allows users to analyze that data for each HIV Envelope protein sequence position and each antibody. 26044712 1 35 theme neutralizing 219:230 arg1 research 241:248 HIV neutralizing antibody research 215:248 HIV neutralizing antibody research 215:248 CATNAP (Compile, Analyze and Tally NAb Panels) is a new web server at Los Alamos HIV Database, created to respond to the newest advances in HIV neutralizing antibody research. 26044712 2 36 theme comprehensive 259:271 arg1 It 251:252 It 251:252 It 251:252 It is a comprehensive platform focusing on neutralizing antibody potencies in conjunction with viral sequences. 26044712 2 36 theme comprehensive 259:271 arg1 platform 273:280 a comprehensive platform 257:280 a comprehensive platform focusing on neutralizing antibody potencies in conjunction with viral sequences 257:360 It is a comprehensive platform focusing on neutralizing antibody potencies in conjunction with viral sequences. 26044712 6 37 theme neutralization 752:765 arg1 data 773:776 neutralization panel data 752:776 neutralization panel data 752:776 The output superimposes neutralization panel data, virus epidemiological data, and viral protein sequence alignments on one page, and provides further information and analyses. 26044712 8 38 theme selected 1346:1353 arg1 antibody 1355:1362 the selected antibody 1342:1362 the selected antibody 1342:1362 The tool calculates tallies of amino acids and N-linked glycosylation motifs, counts of antibody-sensitive and -resistant viruses in conjunction with each amino acid or N-glycosylation motif, and performs Fisher's exact test to detect potential positive or negative amino acid associations for the selected antibody. 26044712 9 39 dep CATNAP 1379:1384 arg1 Compile 1387:1393 Compile 1387:1393 Compile 1387:1393 Website name: CATNAP (Compile, Analyze and Tally NAb Panels). 26044712 9 39 dep CATNAP 1379:1384 arg1 Panels 1418:1423 Tally NAb Panels 1408:1423 Tally NAb Panels 1408:1423 Website name: CATNAP (Compile, Analyze and Tally NAb Panels). 26044712 9 39 dep CATNAP 1379:1384 arg1 Analyze 1396:1402 Analyze 1396:1402 Analyze 1396:1402 Website name: CATNAP (Compile, Analyze and Tally NAb Panels). 26044712 1 40 theme HIV 156:158 arg1 CATNAP 75:80 CATNAP 75:80 CATNAP (Compile, Analyze and Tally NAb Panels) 75:120 CATNAP (Compile, Analyze and Tally NAb Panels) is a new web server at Los Alamos HIV Database, created to respond to the newest advances in HIV neutralizing antibody research. 26044712 1 40 theme HIV 156:158 arg1 Database 160:167 a new web server at Los Alamos HIV Database 125:167 a new web server at Los Alamos HIV Database 125:167 CATNAP (Compile, Analyze and Tally NAb Panels) is a new web server at Los Alamos HIV Database, created to respond to the newest advances in HIV neutralizing antibody research. 26044712 0 41 dep CATNAP 0:5 arg1 tool 10:13 a tool 8:13 CATNAP: a tool to compile, analyze and tally neutralizing antibody panels. 0:73 CATNAP: a tool to compile, analyze and tally neutralizing antibody panels. 26044712 6 42 from alignments 834:843 arg1 page 852:855 one page 848:855 one page 848:855 The output superimposes neutralization panel data, virus epidemiological data, and viral protein sequence alignments on one page, and provides further information and analyses. 26044712 8 43 from counts 1126:1131 arg1 conjunction 1181:1191 conjunction 1181:1191 conjunction with each amino acid 1181:1212 The tool calculates tallies of amino acids and N-linked glycosylation motifs, counts of antibody-sensitive and -resistant viruses in conjunction with each amino acid or N-glycosylation motif, and performs Fisher's exact test to detect potential positive or negative amino acid associations for the selected antibody. 26044712 2 44 with conjunction 329:339 arg1 sequences 352:360 viral sequences 346:360 viral sequences 346:360 It is a comprehensive platform focusing on neutralizing antibody potencies in conjunction with viral sequences. 26044712 10 45 dep Website 1427:1433 arg1 address 1435:1441 address 1435:1441 address 1435:1441 Website address: http://hiv.lanl.gov/catnap. 26044712 6 46 from data 801:804 arg1 page 852:855 one page 848:855 one page 848:855 The output superimposes neutralization panel data, virus epidemiological data, and viral protein sequence alignments on one page, and provides further information and analyses. 26044712 8 47 gly glycosylation 1104:1116 arg1 acids 1085:1089 amino acids 1079:1089 amino acids 1079:1089 The tool calculates tallies of amino acids and N-linked glycosylation motifs, counts of antibody-sensitive and -resistant viruses in conjunction with each amino acid or N-glycosylation motif, and performs Fisher's exact test to detect potential positive or negative amino acid associations for the selected antibody. 26044712 8 47 gly glycosylation 1104:1116 arg2 motifs 1118:1123 tallies of amino acids and N-linked glycosylation motifs 1068:1123 tallies of amino acids and N-linked glycosylation motifs 1068:1123 The tool calculates tallies of amino acids and N-linked glycosylation motifs, counts of antibody-sensitive and -resistant viruses in conjunction with each amino acid or N-glycosylation motif, and performs Fisher's exact test to detect potential positive or negative amino acid associations for the selected antibody. 26044712 9 48 theme Website 1365:1371 arg1 name 1373:1376 Website name 1365:1376 Website name: CATNAP (Compile, Analyze and Tally NAb Panels). 1365:1425 Website name: CATNAP (Compile, Analyze and Tally NAb Panels). 26044712 8 49 theme acids 1085:1089 arg1 tallies 1068:1074 tallies 1068:1074 tallies of amino acids 1068:1089 The tool calculates tallies of amino acids and N-linked glycosylation motifs, counts of antibody-sensitive and -resistant viruses in conjunction with each amino acid or N-glycosylation motif, and performs Fisher's exact test to detect potential positive or negative amino acid associations for the selected antibody. 26044712 8 49 theme acids 1085:1089 arg1 glycosylation 1104:1116 N-linked glycosylation 1095:1116 N-linked glycosylation 1095:1116 The tool calculates tallies of amino acids and N-linked glycosylation motifs, counts of antibody-sensitive and -resistant viruses in conjunction with each amino acid or N-glycosylation motif, and performs Fisher's exact test to detect potential positive or negative amino acid associations for the selected antibody. 26044712 8 50 theme -resistant 1159:1168 arg1 viruses 1170:1176 antibody-sensitive and -resistant viruses 1136:1176 antibody-sensitive and -resistant viruses 1136:1176 The tool calculates tallies of amino acids and N-linked glycosylation motifs, counts of antibody-sensitive and -resistant viruses in conjunction with each amino acid or N-glycosylation motif, and performs Fisher's exact test to detect potential positive or negative amino acid associations for the selected antibody. 26044712 6 51 from data 773:776 arg1 page 852:855 one page 848:855 one page 848:855 The output superimposes neutralization panel data, virus epidemiological data, and viral protein sequence alignments on one page, and provides further information and analyses. 26044712 5 52 theme published 685:693 arg1 study 695:699 a published study 683:699 a published study 683:699 As input, the user can pick specific antibodies and viruses, choose a panel from a published study, or supply their own data. 26044712 7 53 theme view 989:992 arg1 information 1012:1022 view position-specific information 989:1022 view position-specific information from the HIV databases 989:1045 The user can highlight alignment positions, or select antibody contact residues and view position-specific information from the HIV databases. 26044712 1 54 theme new 127:129 arg1 server 135:140 new web server 127:140 a new web server at Los Alamos HIV Database 125:167 CATNAP (Compile, Analyze and Tally NAb Panels) is a new web server at Los Alamos HIV Database, created to respond to the newest advances in HIV neutralizing antibody research. 26044712 8 55 theme N-linked 1095:1102 arg1 glycosylation 1104:1116 N-linked glycosylation 1095:1116 N-linked glycosylation 1095:1116 The tool calculates tallies of amino acids and N-linked glycosylation motifs, counts of antibody-sensitive and -resistant viruses in conjunction with each amino acid or N-glycosylation motif, and performs Fisher's exact test to detect potential positive or negative amino acid associations for the selected antibody. 26044712 7 56 theme position-specific 994:1010 arg1 information 1012:1022 view position-specific information 989:1022 view position-specific information from the HIV databases 989:1045 The user can highlight alignment positions, or select antibody contact residues and view position-specific information from the HIV databases. 26044712 3 57 theme Envelope 489:496 arg1 sequence 506:513 each HIV Envelope protein sequence position and each antibody 480:540 sequence 506:513 CATNAP integrates neutralization and sequence data from published studies, and allows users to analyze that data for each HIV Envelope protein sequence position and each antibody. 26044712 1 58 theme server 135:140 arg1 CATNAP 75:80 CATNAP 75:80 CATNAP (Compile, Analyze and Tally NAb Panels) 75:120 CATNAP (Compile, Analyze and Tally NAb Panels) is a new web server at Los Alamos HIV Database, created to respond to the newest advances in HIV neutralizing antibody research. 26044712 1 58 theme server 135:140 arg1 Database 160:167 a new web server at Los Alamos HIV Database 125:167 a new web server at Los Alamos HIV Database 125:167 CATNAP (Compile, Analyze and Tally NAb Panels) is a new web server at Los Alamos HIV Database, created to respond to the newest advances in HIV neutralizing antibody research. 26044712 1 59 from Alamos 149:154 arg1 server 135:140 new web server 127:140 a new web server at Los Alamos HIV Database 125:167 CATNAP (Compile, Analyze and Tally NAb Panels) is a new web server at Los Alamos HIV Database, created to respond to the newest advances in HIV neutralizing antibody research. 26044712 4 60 theme data 565:568 arg1 retrieval 570:578 multiple data retrieval and analysis options 556:599 retrieval 570:578 The tool has multiple data retrieval and analysis options. 26044712 7 61 theme antibody 959:966 arg1 residues 976:983 antibody contact residues 959:983 antibody contact residues 959:983 The user can highlight alignment positions, or select antibody contact residues and view position-specific information from the HIV databases. 26044712 8 62 theme amino 1203:1207 arg1 acid 1209:1212 each amino acid 1198:1212 each amino acid 1198:1212 The tool calculates tallies of amino acids and N-linked glycosylation motifs, counts of antibody-sensitive and -resistant viruses in conjunction with each amino acid or N-glycosylation motif, and performs Fisher's exact test to detect potential positive or negative amino acid associations for the selected antibody. 26044712 7 63 theme alignment 928:936 arg1 positions 938:946 alignment positions 928:946 alignment positions 928:946 The user can highlight alignment positions, or select antibody contact residues and view position-specific information from the HIV databases. 26044712 8 64 theme antibody-sensitive 1136:1153 arg1 viruses 1170:1176 antibody-sensitive and -resistant viruses 1136:1176 antibody-sensitive and -resistant viruses 1136:1176 The tool calculates tallies of amino acids and N-linked glycosylation motifs, counts of antibody-sensitive and -resistant viruses in conjunction with each amino acid or N-glycosylation motif, and performs Fisher's exact test to detect potential positive or negative amino acid associations for the selected antibody. 26044712 10 65 dep //hiv.lanl.gov/catnap 1449:1469 arg1 Website 1427:1433 Website address 1427:1441 Website address 1427:1441 Website address: http://hiv.lanl.gov/catnap. 26044712 10 65 dep //hiv.lanl.gov/catnap 1449:1469 arg1 http 1444:1447 http 1444:1447 http 1444:1447 Website address: http://hiv.lanl.gov/catnap. 26044712 4 66 contain has 552:554 arg1 tool 547:550 The tool 543:550 The tool 543:550 The tool has multiple data retrieval and analysis options. 26044712 4 66 contain has 552:554 arg2 options 593:599 multiple data retrieval and analysis options 556:599 options 593:599 The tool has multiple data retrieval and analysis options. 26044712 4 66 contain has 552:554 arg2 retrieval 570:578 multiple data retrieval and analysis options 556:599 retrieval 570:578 The tool has multiple data retrieval and analysis options. 26044712 9 67 theme NAb 1414:1416 arg1 Panels 1418:1423 Tally NAb Panels 1408:1423 Tally NAb Panels 1408:1423 Website name: CATNAP (Compile, Analyze and Tally NAb Panels). 26044712 1 68 theme Tally 104:108 arg1 Panels 114:119 Tally NAb Panels 104:119 Tally NAb Panels 104:119 CATNAP (Compile, Analyze and Tally NAb Panels) is a new web server at Los Alamos HIV Database, created to respond to the newest advances in HIV neutralizing antibody research. 26044712 0 69 theme antibody 58:65 arg1 panels 67:72 neutralizing antibody panels 45:72 neutralizing antibody panels 45:72 CATNAP: a tool to compile, analyze and tally neutralizing antibody panels. 26044712 8 70 gly N-glycosylation 1217:1231 arg2 motif 1233:1237 N-glycosylation motif 1217:1237 N-glycosylation motif 1217:1237 The tool calculates tallies of amino acids and N-linked glycosylation motifs, counts of antibody-sensitive and -resistant viruses in conjunction with each amino acid or N-glycosylation motif, and performs Fisher's exact test to detect potential positive or negative amino acid associations for the selected antibody. 26044712 3 71 dep sequence 506:513 arg1 position 515:522 position 515:522 position 515:522 CATNAP integrates neutralization and sequence data from published studies, and allows users to analyze that data for each HIV Envelope protein sequence position and each antibody. 26044712 8 72 from motif 1233:1237 arg1 conjunction 1181:1191 conjunction 1181:1191 conjunction with each amino acid 1181:1212 The tool calculates tallies of amino acids and N-linked glycosylation motifs, counts of antibody-sensitive and -resistant viruses in conjunction with each amino acid or N-glycosylation motif, and performs Fisher's exact test to detect potential positive or negative amino acid associations for the selected antibody. 26044712 8 73 theme exact 1262:1266 arg1 test 1268:1271 Fisher's exact test 1253:1271 Fisher's exact test to detect potential positive or negative amino acid associations for the selected antibody 1253:1362 The tool calculates tallies of amino acids and N-linked glycosylation motifs, counts of antibody-sensitive and -resistant viruses in conjunction with each amino acid or N-glycosylation motif, and performs Fisher's exact test to detect potential positive or negative amino acid associations for the selected antibody. 26044712 8 74 link N-linked 1095:1102 arg1 glycosylation 1104:1116 N-linked glycosylation 1095:1116 N-linked glycosylation 1095:1116 The tool calculates tallies of amino acids and N-linked glycosylation motifs, counts of antibody-sensitive and -resistant viruses in conjunction with each amino acid or N-glycosylation motif, and performs Fisher's exact test to detect potential positive or negative amino acid associations for the selected antibody. 26044712 8 75 theme potential 1283:1291 arg1 associations 1325:1336 potential positive or negative amino acid associations 1283:1336 potential positive or negative amino acid associations for the selected antibody 1283:1362 The tool calculates tallies of amino acids and N-linked glycosylation motifs, counts of antibody-sensitive and -resistant viruses in conjunction with each amino acid or N-glycosylation motif, and performs Fisher's exact test to detect potential positive or negative amino acid associations for the selected antibody. 26044712 2 76 theme antibody 307:314 arg1 potencies 316:324 antibody potencies 307:324 antibody potencies 307:324 It is a comprehensive platform focusing on neutralizing antibody potencies in conjunction with viral sequences. 26044712 3 77 theme published 419:427 arg1 studies 429:435 published studies 419:435 published studies 419:435 CATNAP integrates neutralization and sequence data from published studies, and allows users to analyze that data for each HIV Envelope protein sequence position and each antibody. 26044712 1 78 theme HIV 215:217 arg1 research 241:248 HIV neutralizing antibody research 215:248 HIV neutralizing antibody research 215:248 CATNAP (Compile, Analyze and Tally NAb Panels) is a new web server at Los Alamos HIV Database, created to respond to the newest advances in HIV neutralizing antibody research. 26044712 8 79 theme amino 1314:1318 arg1 associations 1325:1336 potential positive or negative amino acid associations 1283:1336 potential positive or negative amino acid associations for the selected antibody 1283:1362 The tool calculates tallies of amino acids and N-linked glycosylation motifs, counts of antibody-sensitive and -resistant viruses in conjunction with each amino acid or N-glycosylation motif, and performs Fisher's exact test to detect potential positive or negative amino acid associations for the selected antibody. 26044712 1 80 theme antibody 232:239 arg1 research 241:248 HIV neutralizing antibody research 215:248 HIV neutralizing antibody research 215:248 CATNAP (Compile, Analyze and Tally NAb Panels) is a new web server at Los Alamos HIV Database, created to respond to the newest advances in HIV neutralizing antibody research. 26044712 6 81 theme panel 767:771 arg1 data 773:776 neutralization panel data 752:776 neutralization panel data 752:776 The output superimposes neutralization panel data, virus epidemiological data, and viral protein sequence alignments on one page, and provides further information and analyses. 26044712 7 82 from databases 1037:1045 arg1 information 1012:1022 view position-specific information 989:1022 view position-specific information from the HIV databases 989:1045 The user can highlight alignment positions, or select antibody contact residues and view position-specific information from the HIV databases. 26044712 7 82 from databases 1037:1045 arg1 residues 976:983 antibody contact residues 959:983 antibody contact residues 959:983 The user can highlight alignment positions, or select antibody contact residues and view position-specific information from the HIV databases. 26044712 9 83 dep name 1373:1376 arg1 CATNAP 1379:1384 CATNAP 1379:1384 Website name: CATNAP (Compile, Analyze and Tally NAb Panels). 1365:1425 Website name: CATNAP (Compile, Analyze and Tally NAb Panels). 26044712 0 84 dep tool 10:13 arg1 compile 18:24 compile 18:24 compile 18:24 CATNAP: a tool to compile, analyze and tally neutralizing antibody panels. 26044712 0 84 dep tool 10:13 arg1 tally 39:43 tally 39:43 tally neutralizing antibody panels 39:72 CATNAP: a tool to compile, analyze and tally neutralizing antibody panels. 26044712 0 84 dep tool 10:13 arg1 analyze 27:33 analyze 27:33 analyze 27:33 CATNAP: a tool to compile, analyze and tally neutralizing antibody panels. 26044712 4 85 theme multiple 556:563 arg1 retrieval 570:578 multiple data retrieval and analysis options 556:599 retrieval 570:578 The tool has multiple data retrieval and analysis options. 26044712 8 86 with conjunction 1181:1191 arg1 acid 1209:1212 each amino acid 1198:1212 each amino acid 1198:1212 The tool calculates tallies of amino acids and N-linked glycosylation motifs, counts of antibody-sensitive and -resistant viruses in conjunction with each amino acid or N-glycosylation motif, and performs Fisher's exact test to detect potential positive or negative amino acid associations for the selected antibody. 27462433 0 0 theme essential 81:89 arg1 Ncr1 76:79 the NK killer receptor Ncr1 53:79 the NK killer receptor Ncr1 essential for its activity 53:106 Identification of putative novel O-glycosylations in the NK killer receptor Ncr1 essential for its activity. 27462433 4 1 theme settings 457:464 arg1 myriad 417:422 a myriad 415:422 a myriad of pathologies and immunological settings 415:464 NKp46/Ncr1 was shown to be involved in a myriad of pathologies and immunological settings. 27462433 9 2 theme biochemical 1121:1131 arg1 assays 1181:1186 biochemical, mutational and functional in vitro and in vivo assays 1121:1186 biochemical, mutational and functional in vitro and in vivo assays 1121:1186 We next used surface plasmon resonance, biochemical, mutational and functional in vitro and in vivo assays to demonstrate that the putative O-glycosylations of Ncr1 are critical for its function. 27462433 9 3 dep in 1173:1174 arg1 vivo 1176:1179 vivo 1176:1179 vivo 1176:1179 We next used surface plasmon resonance, biochemical, mutational and functional in vitro and in vivo assays to demonstrate that the putative O-glycosylations of Ncr1 are critical for its function. 27462433 9 4 theme Ncr1 1241:1244 arg1 critical 1250:1257 critical 1250:1257 critical 1250:1257 We next used surface plasmon resonance, biochemical, mutational and functional in vitro and in vivo assays to demonstrate that the putative O-glycosylations of Ncr1 are critical for its function. 27462433 9 4 theme Ncr1 1241:1244 arg1 O-glycosylations 1221:1236 O-glycosylations 1221:1236 O-glycosylations 1221:1236 We next used surface plasmon resonance, biochemical, mutational and functional in vitro and in vivo assays to demonstrate that the putative O-glycosylations of Ncr1 are critical for its function. 27462433 8 5 theme liquid 949:954 arg1 chromatography 956:969 high-performance liquid chromatography 932:969 high-performance liquid chromatography analysis 932:978 Here we discovered using prediction algorithms and high-performance liquid chromatography analysis that Ncr1 carries two putative novel O-glycosylations, one of which (Thr 225) is conserved in NKp46. 27462433 1 6 theme tumor 140:144 arg1 cells 165:169 tumor and virus-infected cells 140:169 cells 165:169 Natural killer (NK) cells kill tumor and virus-infected cells using activating NK cell receptors. 27462433 9 7 dep in 1160:1161 arg1 vitro 1163:1167 vitro 1163:1167 vitro 1163:1167 We next used surface plasmon resonance, biochemical, mutational and functional in vitro and in vivo assays to demonstrate that the putative O-glycosylations of Ncr1 are critical for its function. 27462433 0 8 from Identification 0:13 arg1 Ncr1 76:79 the NK killer receptor Ncr1 53:79 the NK killer receptor Ncr1 essential for its activity 53:106 Identification of putative novel O-glycosylations in the NK killer receptor Ncr1 essential for its activity. 27462433 8 9 theme high-performance 932:947 arg1 chromatography 956:969 high-performance liquid chromatography 932:969 high-performance liquid chromatography analysis 932:978 Here we discovered using prediction algorithms and high-performance liquid chromatography analysis that Ncr1 carries two putative novel O-glycosylations, one of which (Thr 225) is conserved in NKp46. 27462433 2 10 theme mouse 265:269 arg1 ortholog 271:278 its mouse ortholog 261:278 its mouse ortholog Ncr1 261:283 One of the major NK-activating receptors is NKp46 and its mouse ortholog Ncr1. 27462433 8 11 theme prediction 906:915 arg1 algorithms 917:926 prediction algorithms 906:926 prediction algorithms 906:926 Here we discovered using prediction algorithms and high-performance liquid chromatography analysis that Ncr1 carries two putative novel O-glycosylations, one of which (Thr 225) is conserved in NKp46. 27462433 4 12 theme pathologies 427:437 arg1 myriad 417:422 a myriad 415:422 a myriad of pathologies and immunological settings 415:464 NKp46/Ncr1 was shown to be involved in a myriad of pathologies and immunological settings. 27462433 8 13 theme O-glycosylations 1017:1032 arg1 O-glycosylations 1017:1032 O-glycosylations 1017:1032 O-glycosylations 1017:1032 Here we discovered using prediction algorithms and high-performance liquid chromatography analysis that Ncr1 carries two putative novel O-glycosylations, one of which (Thr 225) is conserved in NKp46. 27462433 8 13 theme O-glycosylations 1017:1032 arg1 one 1035:1037 one 1035:1037 one 1035:1037 Here we discovered using prediction algorithms and high-performance liquid chromatography analysis that Ncr1 carries two putative novel O-glycosylations, one of which (Thr 225) is conserved in NKp46. 27462433 3 14 theme NK 325:326 arg1 cells 328:332 NK cells 325:332 NK cells 325:332 NKp46/Ncr1 is expressed exclusively on NK cells and on a subset of innate lymphoid cells. 27462433 5 15 theme unknown 568:574 arg1 ligand 591:596 an unknown tumor/cellular ligand 565:596 an unknown tumor/cellular ligand 565:596 Specifically, NKp46/Ncr1 was shown to interact with the viral hemagglutinin (HA) protein and with an unknown tumor/cellular ligand. 27462433 8 16 theme chromatography 956:969 arg1 analysis 971:978 high-performance liquid chromatography analysis 932:978 high-performance liquid chromatography analysis 932:978 Here we discovered using prediction algorithms and high-performance liquid chromatography analysis that Ncr1 carries two putative novel O-glycosylations, one of which (Thr 225) is conserved in NKp46. 27462433 7 17 theme mouse 818:822 arg1 Ncr1 824:827 the mouse Ncr1 814:827 the mouse Ncr1 814:827 Although the human NKp46 carries both O- and N-glycosylations that are essential for its activity, the mouse Ncr1 was predicted to have N-linked glycosylations only. 27462433 4 18 theme immunological 443:455 arg1 settings 457:464 immunological settings 443:464 immunological settings 443:464 NKp46/Ncr1 was shown to be involved in a myriad of pathologies and immunological settings. 27462433 5 19 theme tumor/cellular 576:589 arg1 ligand 591:596 an unknown tumor/cellular ligand 565:596 an unknown tumor/cellular ligand 565:596 Specifically, NKp46/Ncr1 was shown to interact with the viral hemagglutinin (HA) protein and with an unknown tumor/cellular ligand. 27462433 5 20 theme hemagglutinin 529:541 arg1 protein 548:554 the viral hemagglutinin (HA) protein 519:554 the viral hemagglutinin (HA) protein 519:554 Specifically, NKp46/Ncr1 was shown to interact with the viral hemagglutinin (HA) protein and with an unknown tumor/cellular ligand. 27462433 7 21 contain carries 740:746 arg2 N-glycosylations 760:775 N-glycosylations 760:775 N-glycosylations 760:775 Although the human NKp46 carries both O- and N-glycosylations that are essential for its activity, the mouse Ncr1 was predicted to have N-linked glycosylations only. 27462433 7 21 contain carries 740:746 arg1 NKp46 734:738 the human NKp46 724:738 the human NKp46 724:738 Although the human NKp46 carries both O- and N-glycosylations that are essential for its activity, the mouse Ncr1 was predicted to have N-linked glycosylations only. 27462433 7 21 contain carries 740:746 arg2 O- 753:754 O- 753:754 O- 753:754 Although the human NKp46 carries both O- and N-glycosylations that are essential for its activity, the mouse Ncr1 was predicted to have N-linked glycosylations only. 27462433 1 22 theme virus-infected 150:163 arg1 cells 165:169 tumor and virus-infected cells 140:169 cells 165:169 Natural killer (NK) cells kill tumor and virus-infected cells using activating NK cell receptors. 27462433 9 23 used used 1089:1092 arg2 We 1081:1082 We 1081:1082 We 1081:1082 We next used surface plasmon resonance, biochemical, mutational and functional in vitro and in vivo assays to demonstrate that the putative O-glycosylations of Ncr1 are critical for its function. 27462433 3 24 theme innate 353:358 arg1 cells 369:373 innate lymphoid cells 353:373 innate lymphoid cells 353:373 NKp46/Ncr1 is expressed exclusively on NK cells and on a subset of innate lymphoid cells. 27462433 9 25 theme plasmon 1102:1108 arg1 resonance 1110:1118 surface plasmon resonance 1094:1118 surface plasmon resonance 1094:1118 We next used surface plasmon resonance, biochemical, mutational and functional in vitro and in vivo assays to demonstrate that the putative O-glycosylations of Ncr1 are critical for its function. 27462433 9 26 theme in 1173:1174 arg1 assays 1181:1186 biochemical, mutational and functional in vitro and in vivo assays 1121:1186 biochemical, mutational and functional in vitro and in vivo assays 1121:1186 We next used surface plasmon resonance, biochemical, mutational and functional in vitro and in vivo assays to demonstrate that the putative O-glycosylations of Ncr1 are critical for its function. 27462433 9 27 theme mutational 1134:1143 arg1 assays 1181:1186 biochemical, mutational and functional in vitro and in vivo assays 1121:1186 biochemical, mutational and functional in vitro and in vivo assays 1121:1186 We next used surface plasmon resonance, biochemical, mutational and functional in vitro and in vivo assays to demonstrate that the putative O-glycosylations of Ncr1 are critical for its function. 27462433 1 28 theme activating 177:186 arg1 receptors 196:204 activating NK cell receptors 177:204 activating NK cell receptors 177:204 Natural killer (NK) cells kill tumor and virus-infected cells using activating NK cell receptors. 27462433 8 29 dep conserved 1061:1069 arg1 225 1053:1055 Thr 225 1049:1055 Thr 225 1049:1055 Here we discovered using prediction algorithms and high-performance liquid chromatography analysis that Ncr1 carries two putative novel O-glycosylations, one of which (Thr 225) is conserved in NKp46. 27462433 8 30 theme Thr 1049:1051 arg1 225 1053:1055 Thr 225 1049:1055 Thr 225 1049:1055 Here we discovered using prediction algorithms and high-performance liquid chromatography analysis that Ncr1 carries two putative novel O-glycosylations, one of which (Thr 225) is conserved in NKp46. 27462433 1 31 theme NK 188:189 arg1 receptors 196:204 activating NK cell receptors 177:204 activating NK cell receptors 177:204 Natural killer (NK) cells kill tumor and virus-infected cells using activating NK cell receptors. 27462433 2 32 dep ortholog 271:278 arg1 Ncr1 280:283 Ncr1 280:283 its mouse ortholog Ncr1 261:283 One of the major NK-activating receptors is NKp46 and its mouse ortholog Ncr1. 27462433 6 33 from patterns 705:712 arg1 different 672:680 different 672:680 different 672:680 NKp46 and Ncr1 are structurally similar; however, they are substantially different in their glycosylation patterns. 27462433 1 34 theme cell 191:194 arg1 receptors 196:204 activating NK cell receptors 177:204 activating NK cell receptors 177:204 Natural killer (NK) cells kill tumor and virus-infected cells using activating NK cell receptors. 27462433 0 35 theme O-glycosylations 33:48 arg1 Identification 0:13 Identification 0:13 Identification of putative novel O-glycosylations in the NK killer receptor Ncr1 essential for its activity. 0:107 Identification of putative novel O-glycosylations in the NK killer receptor Ncr1 essential for its activity. 27462433 3 36 theme lymphoid 360:367 arg1 cells 369:373 innate lymphoid cells 353:373 innate lymphoid cells 353:373 NKp46/Ncr1 is expressed exclusively on NK cells and on a subset of innate lymphoid cells. 27462433 0 37 theme killer 60:65 arg1 Ncr1 76:79 the NK killer receptor Ncr1 53:79 the NK killer receptor Ncr1 essential for its activity 53:106 Identification of putative novel O-glycosylations in the NK killer receptor Ncr1 essential for its activity. 27462433 1 38 theme Natural 109:115 arg1 NK 125:126 NK 125:126 NK 125:126 Natural killer (NK) cells kill tumor and virus-infected cells using activating NK cell receptors. 27462433 1 38 theme Natural 109:115 arg1 killer 117:122 Natural killer 109:122 Natural killer (NK) cells 109:133 Natural killer (NK) cells kill tumor and virus-infected cells using activating NK cell receptors. 27462433 3 39 theme cells 369:373 arg1 subset 343:348 a subset 341:348 a subset of innate lymphoid cells 341:373 NKp46/Ncr1 is expressed exclusively on NK cells and on a subset of innate lymphoid cells. 27462433 7 40 theme human 728:732 arg1 NKp46 734:738 the human NKp46 724:738 the human NKp46 724:738 Although the human NKp46 carries both O- and N-glycosylations that are essential for its activity, the mouse Ncr1 was predicted to have N-linked glycosylations only. 27462433 7 41 contain have 846:849 arg1 Ncr1 824:827 the mouse Ncr1 814:827 the mouse Ncr1 814:827 Although the human NKp46 carries both O- and N-glycosylations that are essential for its activity, the mouse Ncr1 was predicted to have N-linked glycosylations only. 27462433 7 41 contain have 846:849 arg2 glycosylations 860:873 N-linked glycosylations 851:873 N-linked glycosylations 851:873 Although the human NKp46 carries both O- and N-glycosylations that are essential for its activity, the mouse Ncr1 was predicted to have N-linked glycosylations only. 27462433 1 42 theme killer 117:122 arg1 cells 129:133 Natural killer (NK) cells 109:133 Natural killer (NK) cells 109:133 Natural killer (NK) cells kill tumor and virus-infected cells using activating NK cell receptors. 27462433 7 43 link N-linked 851:858 arg1 glycosylations 860:873 N-linked glycosylations 851:873 N-linked glycosylations 851:873 Although the human NKp46 carries both O- and N-glycosylations that are essential for its activity, the mouse Ncr1 was predicted to have N-linked glycosylations only. 27462433 5 44 theme viral 523:527 arg1 HA 544:545 HA 544:545 HA 544:545 Specifically, NKp46/Ncr1 was shown to interact with the viral hemagglutinin (HA) protein and with an unknown tumor/cellular ligand. 27462433 5 44 theme viral 523:527 arg1 hemagglutinin 529:541 viral hemagglutinin 523:541 the viral hemagglutinin (HA) protein 519:554 Specifically, NKp46/Ncr1 was shown to interact with the viral hemagglutinin (HA) protein and with an unknown tumor/cellular ligand. 27462433 9 45 theme in 1160:1161 arg1 assays 1181:1186 biochemical, mutational and functional in vitro and in vivo assays 1121:1186 biochemical, mutational and functional in vitro and in vivo assays 1121:1186 We next used surface plasmon resonance, biochemical, mutational and functional in vitro and in vivo assays to demonstrate that the putative O-glycosylations of Ncr1 are critical for its function. 27462433 8 46 contain carries 990:996 arg1 Ncr1 985:988 Ncr1 985:988 Ncr1 985:988 Here we discovered using prediction algorithms and high-performance liquid chromatography analysis that Ncr1 carries two putative novel O-glycosylations, one of which (Thr 225) is conserved in NKp46. 27462433 8 46 contain carries 990:996 arg2 algorithms 917:926 prediction algorithms 906:926 prediction algorithms 906:926 Here we discovered using prediction algorithms and high-performance liquid chromatography analysis that Ncr1 carries two putative novel O-glycosylations, one of which (Thr 225) is conserved in NKp46. 27462433 8 46 contain carries 990:996 arg2 analysis 971:978 high-performance liquid chromatography analysis 932:978 high-performance liquid chromatography analysis 932:978 Here we discovered using prediction algorithms and high-performance liquid chromatography analysis that Ncr1 carries two putative novel O-glycosylations, one of which (Thr 225) is conserved in NKp46. 27462433 8 46 contain carries 990:996 arg2 O-glycosylations 1017:1032 O-glycosylations 1017:1032 O-glycosylations 1017:1032 Here we discovered using prediction algorithms and high-performance liquid chromatography analysis that Ncr1 carries two putative novel O-glycosylations, one of which (Thr 225) is conserved in NKp46. 27462433 9 47 theme surface 1094:1100 arg1 resonance 1110:1118 surface plasmon resonance 1094:1118 surface plasmon resonance 1094:1118 We next used surface plasmon resonance, biochemical, mutational and functional in vitro and in vivo assays to demonstrate that the putative O-glycosylations of Ncr1 are critical for its function. 27462433 2 48 theme receptors 238:246 arg1 receptors 238:246 the major NK-activating receptors 214:246 the major NK-activating receptors 214:246 One of the major NK-activating receptors is NKp46 and its mouse ortholog Ncr1. 27462433 2 48 theme receptors 238:246 arg1 One 207:209 One 207:209 One 207:209 One of the major NK-activating receptors is NKp46 and its mouse ortholog Ncr1. 27462433 6 49 theme glycosylation 691:703 arg1 patterns 705:712 their glycosylation patterns 685:712 their glycosylation patterns 685:712 NKp46 and Ncr1 are structurally similar; however, they are substantially different in their glycosylation patterns. 27462433 9 50 theme functional 1149:1158 arg1 assays 1181:1186 biochemical, mutational and functional in vitro and in vivo assays 1121:1186 biochemical, mutational and functional in vitro and in vivo assays 1121:1186 We next used surface plasmon resonance, biochemical, mutational and functional in vitro and in vivo assays to demonstrate that the putative O-glycosylations of Ncr1 are critical for its function. 27462433 0 51 theme receptor 67:74 arg1 Ncr1 76:79 the NK killer receptor Ncr1 53:79 the NK killer receptor Ncr1 essential for its activity 53:106 Identification of putative novel O-glycosylations in the NK killer receptor Ncr1 essential for its activity. 27462433 2 52 theme NK-activating 224:236 arg1 receptors 238:246 the major NK-activating receptors 214:246 the major NK-activating receptors 214:246 One of the major NK-activating receptors is NKp46 and its mouse ortholog Ncr1. 27462433 7 53 theme N-linked 851:858 arg1 glycosylations 860:873 N-linked glycosylations 851:873 N-linked glycosylations 851:873 Although the human NKp46 carries both O- and N-glycosylations that are essential for its activity, the mouse Ncr1 was predicted to have N-linked glycosylations only. 27462433 0 54 theme NK 57:58 arg1 Ncr1 76:79 the NK killer receptor Ncr1 53:79 the NK killer receptor Ncr1 essential for its activity 53:106 Identification of putative novel O-glycosylations in the NK killer receptor Ncr1 essential for its activity. 27462433 2 55 theme major 218:222 arg1 receptors 238:246 the major NK-activating receptors 214:246 the major NK-activating receptors 214:246 One of the major NK-activating receptors is NKp46 and its mouse ortholog Ncr1. 27462433 6 56 from different 672:680 arg1 patterns 705:712 their glycosylation patterns 685:712 their glycosylation patterns 685:712 NKp46 and Ncr1 are structurally similar; however, they are substantially different in their glycosylation patterns. 25132301 5 0 theme ion 637:639 arg1 properties 650:659 the CID and ion mobility properties 625:659 properties 650:659 This paper examines the CID and ion mobility properties of these endoH-released glycans to determine if the missing GlcNAc influences the production of diagnostic fragment ions. 25132301 6 1 theme ribonuclease 820:831 arg1 B 833:833 ribonuclease B 820:833 ribonuclease B 820:833 METHODS N-Glycans were released from ribonuclease B, ovalbumin and gp120 with endoH to give high-mannose and hybrid glycans, and from IgG with endoS to produce biantennary complex glycans, all missing the reducing-terminal GlcNAc residue. 25132301 2 2 theme dissociation 165:176 arg1 spectra 184:190 RATIONALE Negative ion collision-induced dissociation (CID) spectra 124:190 RATIONALE Negative ion collision-induced dissociation (CID) spectra of N-glycans 124:203 RATIONALE Negative ion collision-induced dissociation (CID) spectra of N-glycans contain many diagnostic ions that provide more structural information than positive ion spectra. 25132301 7 3 theme Waters 1101:1106 arg1 spectrometer 1123:1134 a Waters Synapt G2 mass spectrometer 1099:1134 a Waters Synapt G2 mass spectrometer using nanospray sample introduction 1099:1170 Negative ion CID and travelling wave ion mobility spectra were recorded with a Waters Synapt G2 mass spectrometer using nanospray sample introduction. 25132301 11 4 theme PNGase 1853:1858 arg1 F 1860:1860 PNGase F 1853:1860 PNGase F 1853:1860 CONCLUSIONS The results show that the CID spectra of endoH- and endoS-released glycans are as useful as the corresponding spectra of the intact glycans (as released by PNGase F) in providing structural information on N-glycans. 25132301 8 5 theme same 1240:1243 arg1 informative 1291:1301 informative 1291:1301 informative 1291:1301 RESULTS The majority of glycans yielded CID spectra exhibiting the same diagnostic fragments, which were equivalently informative, as the fully released structures. 25132301 8 5 theme same 1240:1243 arg1 fragments 1256:1264 the same diagnostic fragments 1236:1264 the same diagnostic fragments 1236:1264 RESULTS The majority of glycans yielded CID spectra exhibiting the same diagnostic fragments, which were equivalently informative, as the fully released structures. 25132301 2 6 theme ion 143:145 arg1 spectra 184:190 RATIONALE Negative ion collision-induced dissociation (CID) spectra 124:190 RATIONALE Negative ion collision-induced dissociation (CID) spectra of N-glycans 124:203 RATIONALE Negative ion collision-induced dissociation (CID) spectra of N-glycans contain many diagnostic ions that provide more structural information than positive ion spectra. 25132301 11 7 dep CONCLUSIONS 1685:1695 arg1 show 1709:1712 show 1709:1712 show that the CID spectra of endoH- and endoS-released glycans are as useful as the corresponding spectra of the intact glycans (as released by PNGase F) in providing structural information on N-glycans 1709:1910 CONCLUSIONS The results show that the CID spectra of endoH- and endoS-released glycans are as useful as the corresponding spectra of the intact glycans (as released by PNGase F) in providing structural information on N-glycans. 25132301 2 8 theme positive 280:287 arg1 spectra 293:299 positive ion spectra 280:299 positive ion spectra 280:299 RATIONALE Negative ion collision-induced dissociation (CID) spectra of N-glycans contain many diagnostic ions that provide more structural information than positive ion spectra. 25132301 10 9 theme monogalactosylated 1574:1591 arg1 glycans 1593:1599 biantennary monogalactosylated glycans 1562:1599 biantennary monogalactosylated glycans from IgG 1562:1608 The exception was the partial resolution of a pair of biantennary monogalactosylated glycans from IgG where, as chloride adducts, slight separation of the isomers was observed. 25132301 7 10 theme G2 1115:1116 arg1 spectrometer 1123:1134 a Waters Synapt G2 mass spectrometer 1099:1134 a Waters Synapt G2 mass spectrometer using nanospray sample introduction 1099:1170 Negative ion CID and travelling wave ion mobility spectra were recorded with a Waters Synapt G2 mass spectrometer using nanospray sample introduction. 25132301 8 11 theme glycans 1197:1203 arg1 majority 1185:1192 The majority 1181:1192 The majority of glycans 1181:1203 RESULTS The majority of glycans yielded CID spectra exhibiting the same diagnostic fragments, which were equivalently informative, as the fully released structures. 25132301 6 12 theme complex 955:961 arg1 all 972:974 all 972:974 all 972:974 METHODS N-Glycans were released from ribonuclease B, ovalbumin and gp120 with endoH to give high-mannose and hybrid glycans, and from IgG with endoS to produce biantennary complex glycans, all missing the reducing-terminal GlcNAc residue. 25132301 6 12 theme complex 955:961 arg1 glycans 963:969 biantennary complex glycans 943:969 biantennary complex glycans 943:969 METHODS N-Glycans were released from ribonuclease B, ovalbumin and gp120 with endoH to give high-mannose and hybrid glycans, and from IgG with endoS to produce biantennary complex glycans, all missing the reducing-terminal GlcNAc residue. 25132301 11 13 theme glycans 1764:1770 arg1 spectra 1727:1733 the CID spectra 1719:1733 the CID spectra of endoH- and endoS-released glycans 1719:1770 CONCLUSIONS The results show that the CID spectra of endoH- and endoS-released glycans are as useful as the corresponding spectra of the intact glycans (as released by PNGase F) in providing structural information on N-glycans. 25132301 7 14 theme mobility 1063:1070 arg1 spectra 1072:1078 ion mobility spectra 1059:1078 ion mobility spectra 1059:1078 Negative ion CID and travelling wave ion mobility spectra were recorded with a Waters Synapt G2 mass spectrometer using nanospray sample introduction. 25132301 9 15 theme full 1450:1453 arg1 glycans 1455:1461 the full glycans 1446:1461 the full glycans 1446:1461 However, the ability of ion mobility to separate isomers was generally found to be inferior to its use with the full glycans despite the smaller nature of the compounds. 25132301 8 16 theme CID 1213:1215 arg1 spectra 1217:1223 CID spectra 1213:1223 CID spectra exhibiting the same diagnostic fragments, which were equivalently informative, as the fully released structures 1213:1335 RESULTS The majority of glycans yielded CID spectra exhibiting the same diagnostic fragments, which were equivalently informative, as the fully released structures. 25132301 11 17 theme corresponding 1793:1805 arg1 spectra 1807:1813 the corresponding spectra 1789:1813 the corresponding spectra of the intact glycans (as released by PNGase F) 1789:1861 CONCLUSIONS The results show that the CID spectra of endoH- and endoS-released glycans are as useful as the corresponding spectra of the intact glycans (as released by PNGase F) in providing structural information on N-glycans. 25132301 7 18 theme sample 1152:1157 arg1 introduction 1159:1170 nanospray sample introduction 1142:1170 nanospray sample introduction 1142:1170 Negative ion CID and travelling wave ion mobility spectra were recorded with a Waters Synapt G2 mass spectrometer using nanospray sample introduction. 25132301 10 19 theme pair 1554:1557 arg1 exception 1512:1520 The exception 1508:1520 The exception 1508:1520 The exception was the partial resolution of a pair of biantennary monogalactosylated glycans from IgG where, as chloride adducts, slight separation of the isomers was observed. 25132301 10 19 theme pair 1554:1557 arg1 resolution 1538:1547 the partial resolution 1526:1547 the partial resolution of a pair of biantennary monogalactosylated glycans from IgG 1526:1608 The exception was the partial resolution of a pair of biantennary monogalactosylated glycans from IgG where, as chloride adducts, slight separation of the isomers was observed. 25132301 3 20 theme endoS 311:315 arg1 release 317:323 endoS release 311:323 endoS release 311:323 EndoH or endoS release of glycans from glycoproteins, as used by many investigators, cleaves glycans between the GlcNAc residues of the chitobiose core leaving the glycan without the reducing-terminal GlcNAc residue. 25132301 7 21 theme Negative 1022:1029 arg1 CID 1035:1037 Negative ion CID 1022:1037 Negative ion CID 1022:1037 Negative ion CID and travelling wave ion mobility spectra were recorded with a Waters Synapt G2 mass spectrometer using nanospray sample introduction. 25132301 2 22 theme diagnostic 218:227 arg1 ions 229:232 many diagnostic ions 213:232 many diagnostic ions that provide more structural information than positive ion spectra 213:299 RATIONALE Negative ion collision-induced dissociation (CID) spectra of N-glycans contain many diagnostic ions that provide more structural information than positive ion spectra. 25132301 9 23 theme smaller 1475:1481 arg1 nature 1483:1488 the smaller nature 1471:1488 the smaller nature of the compounds 1471:1505 However, the ability of ion mobility to separate isomers was generally found to be inferior to its use with the full glycans despite the smaller nature of the compounds. 25132301 11 24 theme CID 1723:1725 arg1 spectra 1727:1733 the CID spectra 1719:1733 the CID spectra of endoH- and endoS-released glycans 1719:1770 CONCLUSIONS The results show that the CID spectra of endoH- and endoS-released glycans are as useful as the corresponding spectra of the intact glycans (as released by PNGase F) in providing structural information on N-glycans. 25132301 7 25 theme ion 1031:1033 arg1 CID 1035:1037 Negative ion CID 1022:1037 Negative ion CID 1022:1037 Negative ion CID and travelling wave ion mobility spectra were recorded with a Waters Synapt G2 mass spectrometer using nanospray sample introduction. 25132301 8 26 theme released 1317:1324 arg1 structures 1326:1335 the fully released structures 1307:1335 the fully released structures 1307:1335 RESULTS The majority of glycans yielded CID spectra exhibiting the same diagnostic fragments, which were equivalently informative, as the fully released structures. 25132301 9 27 theme compounds 1497:1505 arg1 nature 1483:1488 the smaller nature 1471:1488 the smaller nature of the compounds 1471:1505 However, the ability of ion mobility to separate isomers was generally found to be inferior to its use with the full glycans despite the smaller nature of the compounds. 25132301 6 28 theme reducing-terminal 988:1004 arg1 residue 1013:1019 the reducing-terminal GlcNAc residue 984:1019 the reducing-terminal GlcNAc residue 984:1019 METHODS N-Glycans were released from ribonuclease B, ovalbumin and gp120 with endoH to give high-mannose and hybrid glycans, and from IgG with endoS to produce biantennary complex glycans, all missing the reducing-terminal GlcNAc residue. 25132301 8 29 dep RESULTS 1173:1179 arg1 yielded 1205:1211 yielded 1205:1211 yielded CID spectra exhibiting the same diagnostic fragments, which were equivalently informative, as the fully released structures 1205:1335 RESULTS The majority of glycans yielded CID spectra exhibiting the same diagnostic fragments, which were equivalently informative, as the fully released structures. 25132301 5 30 theme glycans 685:691 arg1 CID 629:631 the CID and ion mobility properties 625:659 CID 629:631 This paper examines the CID and ion mobility properties of these endoH-released glycans to determine if the missing GlcNAc influences the production of diagnostic fragment ions. 25132301 5 30 theme glycans 685:691 arg1 properties 650:659 the CID and ion mobility properties 625:659 properties 650:659 This paper examines the CID and ion mobility properties of these endoH-released glycans to determine if the missing GlcNAc influences the production of diagnostic fragment ions. 25132301 10 31 from IgG 1606:1608 arg1 glycans 1593:1599 biantennary monogalactosylated glycans 1562:1599 biantennary monogalactosylated glycans from IgG 1562:1608 The exception was the partial resolution of a pair of biantennary monogalactosylated glycans from IgG where, as chloride adducts, slight separation of the isomers was observed. 25132301 10 31 from IgG 1606:1608 arg1 pair 1554:1557 a pair 1552:1557 a pair of biantennary monogalactosylated glycans from IgG 1552:1608 The exception was the partial resolution of a pair of biantennary monogalactosylated glycans from IgG where, as chloride adducts, slight separation of the isomers was observed. 25132301 5 32 theme fragment 768:775 arg1 ions 777:780 diagnostic fragment ions 757:780 diagnostic fragment ions 757:780 This paper examines the CID and ion mobility properties of these endoH-released glycans to determine if the missing GlcNAc influences the production of diagnostic fragment ions. 25132301 0 33 from carbohydrates 45:57 arg1 Fragmentation 0:12 Fragmentation 0:12 Fragmentation of negative ions from N-linked carbohydrates: part 6. 0:66 Fragmentation of negative ions from N-linked carbohydrates: part 6. 25132301 0 34 theme N-linked 36:43 arg1 carbohydrates 45:57 N-linked carbohydrates 36:57 N-linked carbohydrates 36:57 Fragmentation of negative ions from N-linked carbohydrates: part 6. 25132301 11 35 dep glycans 1829:1835 arg1 released 1841:1848 released 1841:1848 released by PNGase F 1841:1860 CONCLUSIONS The results show that the CID spectra of endoH- and endoS-released glycans are as useful as the corresponding spectra of the intact glycans (as released by PNGase F) in providing structural information on N-glycans. 25132301 10 36 theme chloride 1620:1627 arg1 adducts 1629:1635 chloride adducts 1620:1635 chloride adducts 1620:1635 The exception was the partial resolution of a pair of biantennary monogalactosylated glycans from IgG where, as chloride adducts, slight separation of the isomers was observed. 25132301 10 36 theme chloride 1620:1627 arg1 separation 1645:1654 slight separation 1638:1654 slight separation of the isomers 1638:1669 The exception was the partial resolution of a pair of biantennary monogalactosylated glycans from IgG where, as chloride adducts, slight separation of the isomers was observed. 25132301 3 37 theme many 367:370 arg1 investigators 372:384 many investigators 367:384 many investigators 367:384 EndoH or endoS release of glycans from glycoproteins, as used by many investigators, cleaves glycans between the GlcNAc residues of the chitobiose core leaving the glycan without the reducing-terminal GlcNAc residue. 25132301 0 38 theme negative 17:24 arg1 ions 26:29 negative ions 17:29 negative ions 17:29 Fragmentation of negative ions from N-linked carbohydrates: part 6. 25132301 6 39 with B 833:833 arg1 endoH 861:865 endoH 861:865 endoH 861:865 METHODS N-Glycans were released from ribonuclease B, ovalbumin and gp120 with endoH to give high-mannose and hybrid glycans, and from IgG with endoS to produce biantennary complex glycans, all missing the reducing-terminal GlcNAc residue. 25132301 3 40 theme core 449:452 arg1 residues 422:429 the GlcNAc residues 411:429 the GlcNAc residues of the chitobiose core leaving the glycan without the reducing-terminal GlcNAc residue 411:516 EndoH or endoS release of glycans from glycoproteins, as used by many investigators, cleaves glycans between the GlcNAc residues of the chitobiose core leaving the glycan without the reducing-terminal GlcNAc residue. 25132301 3 40 theme core 449:452 arg1 core 449:452 the chitobiose core 434:452 the chitobiose core leaving the glycan without the reducing-terminal GlcNAc residue 434:516 EndoH or endoS release of glycans from glycoproteins, as used by many investigators, cleaves glycans between the GlcNAc residues of the chitobiose core leaving the glycan without the reducing-terminal GlcNAc residue. 25132301 7 41 theme nanospray 1142:1150 arg1 introduction 1159:1170 nanospray sample introduction 1142:1170 nanospray sample introduction 1142:1170 Negative ion CID and travelling wave ion mobility spectra were recorded with a Waters Synapt G2 mass spectrometer using nanospray sample introduction. 25132301 9 42 with use 1437:1439 arg1 glycans 1455:1461 the full glycans 1446:1461 the full glycans 1446:1461 However, the ability of ion mobility to separate isomers was generally found to be inferior to its use with the full glycans despite the smaller nature of the compounds. 25132301 3 43 theme reducing-terminal 485:501 arg1 residue 510:516 the reducing-terminal GlcNAc residue 481:516 the reducing-terminal GlcNAc residue 481:516 EndoH or endoS release of glycans from glycoproteins, as used by many investigators, cleaves glycans between the GlcNAc residues of the chitobiose core leaving the glycan without the reducing-terminal GlcNAc residue. 25132301 9 44 theme mobility 1366:1373 arg1 ability 1351:1357 the ability 1347:1357 the ability of ion mobility to separate isomers 1347:1393 However, the ability of ion mobility to separate isomers was generally found to be inferior to its use with the full glycans despite the smaller nature of the compounds. 25132301 9 44 theme mobility 1366:1373 arg1 inferior 1421:1428 inferior 1421:1428 inferior 1421:1428 However, the ability of ion mobility to separate isomers was generally found to be inferior to its use with the full glycans despite the smaller nature of the compounds. 25132301 4 45 theme ion 543:545 arg1 spectra 551:557 their negative ion CID spectra 528:557 their negative ion CID spectra 528:557 However, their negative ion CID spectra do not appear to have been studied in detail. 25132301 9 46 theme separate 1378:1385 arg1 isomers 1387:1393 separate isomers 1378:1393 separate isomers 1378:1393 However, the ability of ion mobility to separate isomers was generally found to be inferior to its use with the full glycans despite the smaller nature of the compounds. 25132301 10 47 from pair 1554:1557 arg1 IgG 1606:1608 IgG 1606:1608 IgG 1606:1608 The exception was the partial resolution of a pair of biantennary monogalactosylated glycans from IgG where, as chloride adducts, slight separation of the isomers was observed. 25132301 10 48 theme partial 1530:1536 arg1 exception 1512:1520 The exception 1508:1520 The exception 1508:1520 The exception was the partial resolution of a pair of biantennary monogalactosylated glycans from IgG where, as chloride adducts, slight separation of the isomers was observed. 25132301 10 48 theme partial 1530:1536 arg1 resolution 1538:1547 the partial resolution 1526:1547 the partial resolution of a pair of biantennary monogalactosylated glycans from IgG 1526:1608 The exception was the partial resolution of a pair of biantennary monogalactosylated glycans from IgG where, as chloride adducts, slight separation of the isomers was observed. 25132301 11 49 theme structural 1876:1885 arg1 information 1887:1897 structural information 1876:1897 structural information on N-glycans 1876:1910 CONCLUSIONS The results show that the CID spectra of endoH- and endoS-released glycans are as useful as the corresponding spectra of the intact glycans (as released by PNGase F) in providing structural information on N-glycans. 25132301 0 50 dep Fragmentation 0:12 arg1 part 60:63 part 6 60:65 Fragmentation of negative ions from N-linked carbohydrates: part 6. 0:66 Fragmentation of negative ions from N-linked carbohydrates: part 6. 25132301 7 51 theme Synapt 1108:1113 arg1 spectrometer 1123:1134 a Waters Synapt G2 mass spectrometer 1099:1134 a Waters Synapt G2 mass spectrometer using nanospray sample introduction 1099:1170 Negative ion CID and travelling wave ion mobility spectra were recorded with a Waters Synapt G2 mass spectrometer using nanospray sample introduction. 25132301 10 52 dep resolution 1538:1547 arg1 observed 1675:1682 observed 1675:1682 was observed 1671:1682 The exception was the partial resolution of a pair of biantennary monogalactosylated glycans from IgG where, as chloride adducts, slight separation of the isomers was observed. 25132301 3 53 dep EndoH 302:306 arg1 used 359:362 used 359:362 used by many investigators 359:384 EndoH or endoS release of glycans from glycoproteins, as used by many investigators, cleaves glycans between the GlcNAc residues of the chitobiose core leaving the glycan without the reducing-terminal GlcNAc residue. 25132301 5 54 theme mobility 641:648 arg1 properties 650:659 the CID and ion mobility properties 625:659 properties 650:659 This paper examines the CID and ion mobility properties of these endoH-released glycans to determine if the missing GlcNAc influences the production of diagnostic fragment ions. 25132301 6 55 theme hybrid 892:897 arg1 glycans 899:905 high-mannose and hybrid glycans 875:905 glycans 899:905 METHODS N-Glycans were released from ribonuclease B, ovalbumin and gp120 with endoH to give high-mannose and hybrid glycans, and from IgG with endoS to produce biantennary complex glycans, all missing the reducing-terminal GlcNAc residue. 25132301 7 56 dep CID 1035:1037 arg1 spectra 1072:1078 ion mobility spectra 1059:1078 ion mobility spectra 1059:1078 Negative ion CID and travelling wave ion mobility spectra were recorded with a Waters Synapt G2 mass spectrometer using nanospray sample introduction. 25132301 2 57 theme collision-induced 147:163 arg1 spectra 184:190 RATIONALE Negative ion collision-induced dissociation (CID) spectra 124:190 RATIONALE Negative ion collision-induced dissociation (CID) spectra of N-glycans 124:203 RATIONALE Negative ion collision-induced dissociation (CID) spectra of N-glycans contain many diagnostic ions that provide more structural information than positive ion spectra. 25132301 2 58 theme ion 289:291 arg1 spectra 293:299 positive ion spectra 280:299 positive ion spectra 280:299 RATIONALE Negative ion collision-induced dissociation (CID) spectra of N-glycans contain many diagnostic ions that provide more structural information than positive ion spectra. 25132301 6 59 attach released 806:813 arg1 B 833:833 ribonuclease B 820:833 ribonuclease B 820:833 METHODS N-Glycans were released from ribonuclease B, ovalbumin and gp120 with endoH to give high-mannose and hybrid glycans, and from IgG with endoS to produce biantennary complex glycans, all missing the reducing-terminal GlcNAc residue. 25132301 6 59 attach released 806:813 arg2 N-Glycans 791:799 METHODS N-Glycans 783:799 METHODS N-Glycans 783:799 METHODS N-Glycans were released from ribonuclease B, ovalbumin and gp120 with endoH to give high-mannose and hybrid glycans, and from IgG with endoS to produce biantennary complex glycans, all missing the reducing-terminal GlcNAc residue. 25132301 6 59 attach released 806:813 arg1 IgG 917:919 IgG 917:919 IgG with endoS to produce biantennary complex glycans, all missing the reducing-terminal GlcNAc residue 917:1019 METHODS N-Glycans were released from ribonuclease B, ovalbumin and gp120 with endoH to give high-mannose and hybrid glycans, and from IgG with endoS to produce biantennary complex glycans, all missing the reducing-terminal GlcNAc residue. 25132301 6 60 theme high-mannose 875:886 arg1 glycans 899:905 high-mannose and hybrid glycans 875:905 glycans 899:905 METHODS N-Glycans were released from ribonuclease B, ovalbumin and gp120 with endoH to give high-mannose and hybrid glycans, and from IgG with endoS to produce biantennary complex glycans, all missing the reducing-terminal GlcNAc residue. 25132301 10 61 theme glycans 1593:1599 arg1 pair 1554:1557 a pair 1552:1557 a pair of biantennary monogalactosylated glycans from IgG 1552:1608 The exception was the partial resolution of a pair of biantennary monogalactosylated glycans from IgG where, as chloride adducts, slight separation of the isomers was observed. 25132301 2 62 theme Negative 134:141 arg1 spectra 184:190 RATIONALE Negative ion collision-induced dissociation (CID) spectra 124:190 RATIONALE Negative ion collision-induced dissociation (CID) spectra of N-glycans 124:203 RATIONALE Negative ion collision-induced dissociation (CID) spectra of N-glycans contain many diagnostic ions that provide more structural information than positive ion spectra. 25132301 6 63 theme METHODS 783:789 arg1 N-Glycans 791:799 METHODS N-Glycans 783:799 METHODS N-Glycans 783:799 METHODS N-Glycans were released from ribonuclease B, ovalbumin and gp120 with endoH to give high-mannose and hybrid glycans, and from IgG with endoS to produce biantennary complex glycans, all missing the reducing-terminal GlcNAc residue. 25132301 0 64 link N-linked 36:43 arg1 carbohydrates 45:57 N-linked carbohydrates 36:57 N-linked carbohydrates 36:57 Fragmentation of negative ions from N-linked carbohydrates: part 6. 25132301 6 65 with IgG 917:919 arg1 endoS 926:930 endoS 926:930 endoS 926:930 METHODS N-Glycans were released from ribonuclease B, ovalbumin and gp120 with endoH to give high-mannose and hybrid glycans, and from IgG with endoS to produce biantennary complex glycans, all missing the reducing-terminal GlcNAc residue. 25132301 8 66 theme diagnostic 1245:1254 arg1 informative 1291:1301 informative 1291:1301 informative 1291:1301 RESULTS The majority of glycans yielded CID spectra exhibiting the same diagnostic fragments, which were equivalently informative, as the fully released structures. 25132301 8 66 theme diagnostic 1245:1254 arg1 fragments 1256:1264 the same diagnostic fragments 1236:1264 the same diagnostic fragments 1236:1264 RESULTS The majority of glycans yielded CID spectra exhibiting the same diagnostic fragments, which were equivalently informative, as the fully released structures. 25132301 10 67 theme biantennary 1562:1572 arg1 glycans 1593:1599 biantennary monogalactosylated glycans 1562:1599 biantennary monogalactosylated glycans from IgG 1562:1608 The exception was the partial resolution of a pair of biantennary monogalactosylated glycans from IgG where, as chloride adducts, slight separation of the isomers was observed. 25132301 7 68 theme ion 1059:1061 arg1 spectra 1072:1078 ion mobility spectra 1059:1078 ion mobility spectra 1059:1078 Negative ion CID and travelling wave ion mobility spectra were recorded with a Waters Synapt G2 mass spectrometer using nanospray sample introduction. 25132301 6 69 theme biantennary 943:953 arg1 all 972:974 all 972:974 all 972:974 METHODS N-Glycans were released from ribonuclease B, ovalbumin and gp120 with endoH to give high-mannose and hybrid glycans, and from IgG with endoS to produce biantennary complex glycans, all missing the reducing-terminal GlcNAc residue. 25132301 6 69 theme biantennary 943:953 arg1 glycans 963:969 biantennary complex glycans 943:969 biantennary complex glycans 943:969 METHODS N-Glycans were released from ribonuclease B, ovalbumin and gp120 with endoH to give high-mannose and hybrid glycans, and from IgG with endoS to produce biantennary complex glycans, all missing the reducing-terminal GlcNAc residue. 25132301 11 70 theme glycans 1829:1835 arg1 spectra 1807:1813 the corresponding spectra 1789:1813 the corresponding spectra of the intact glycans (as released by PNGase F) 1789:1861 CONCLUSIONS The results show that the CID spectra of endoH- and endoS-released glycans are as useful as the corresponding spectra of the intact glycans (as released by PNGase F) in providing structural information on N-glycans. 25132301 7 71 theme travelling 1043:1052 arg1 wave 1054:1057 travelling wave 1043:1057 travelling wave 1043:1057 Negative ion CID and travelling wave ion mobility spectra were recorded with a Waters Synapt G2 mass spectrometer using nanospray sample introduction. 25132301 2 72 contain contain 205:211 arg1 spectra 184:190 RATIONALE Negative ion collision-induced dissociation (CID) spectra 124:190 RATIONALE Negative ion collision-induced dissociation (CID) spectra of N-glycans 124:203 RATIONALE Negative ion collision-induced dissociation (CID) spectra of N-glycans contain many diagnostic ions that provide more structural information than positive ion spectra. 25132301 2 72 contain contain 205:211 arg2 ions 229:232 many diagnostic ions 213:232 many diagnostic ions that provide more structural information than positive ion spectra 213:299 RATIONALE Negative ion collision-induced dissociation (CID) spectra of N-glycans contain many diagnostic ions that provide more structural information than positive ion spectra. 25132301 11 73 from information 1887:1897 arg1 N-glycans 1902:1910 N-glycans 1902:1910 N-glycans 1902:1910 CONCLUSIONS The results show that the CID spectra of endoH- and endoS-released glycans are as useful as the corresponding spectra of the intact glycans (as released by PNGase F) in providing structural information on N-glycans. 25132301 5 74 theme endoH-released 670:683 arg1 glycans 685:691 these endoH-released glycans 664:691 these endoH-released glycans 664:691 This paper examines the CID and ion mobility properties of these endoH-released glycans to determine if the missing GlcNAc influences the production of diagnostic fragment ions. 25132301 3 75 from glycoproteins 341:353 arg1 glycans 328:334 glycans 328:334 glycans from glycoproteins 328:353 EndoH or endoS release of glycans from glycoproteins, as used by many investigators, cleaves glycans between the GlcNAc residues of the chitobiose core leaving the glycan without the reducing-terminal GlcNAc residue. 25132301 3 75 from glycoproteins 341:353 arg1 EndoH 302:306 EndoH 302:306 EndoH 302:306 EndoH or endoS release of glycans from glycoproteins, as used by many investigators, cleaves glycans between the GlcNAc residues of the chitobiose core leaving the glycan without the reducing-terminal GlcNAc residue. 25132301 3 75 from glycoproteins 341:353 arg1 release 317:323 endoS release 311:323 endoS release 311:323 EndoH or endoS release of glycans from glycoproteins, as used by many investigators, cleaves glycans between the GlcNAc residues of the chitobiose core leaving the glycan without the reducing-terminal GlcNAc residue. 25132301 2 76 theme structural 252:261 arg1 information 263:273 more structural information 247:273 more structural information than positive ion spectra 247:299 RATIONALE Negative ion collision-induced dissociation (CID) spectra of N-glycans contain many diagnostic ions that provide more structural information than positive ion spectra. 25132301 6 77 theme GlcNAc 1006:1011 arg1 residue 1013:1019 the reducing-terminal GlcNAc residue 984:1019 the reducing-terminal GlcNAc residue 984:1019 METHODS N-Glycans were released from ribonuclease B, ovalbumin and gp120 with endoH to give high-mannose and hybrid glycans, and from IgG with endoS to produce biantennary complex glycans, all missing the reducing-terminal GlcNAc residue. 25132301 3 78 from EndoH 302:306 arg1 glycoproteins 341:353 glycoproteins 341:353 glycoproteins 341:353 EndoH or endoS release of glycans from glycoproteins, as used by many investigators, cleaves glycans between the GlcNAc residues of the chitobiose core leaving the glycan without the reducing-terminal GlcNAc residue. 25132301 5 79 theme diagnostic 757:766 arg1 ions 777:780 diagnostic fragment ions 757:780 diagnostic fragment ions 757:780 This paper examines the CID and ion mobility properties of these endoH-released glycans to determine if the missing GlcNAc influences the production of diagnostic fragment ions. 25132301 11 80 theme intact 1822:1827 arg1 glycans 1829:1835 the intact glycans 1818:1835 the intact glycans (as released by PNGase F) 1818:1861 CONCLUSIONS The results show that the CID spectra of endoH- and endoS-released glycans are as useful as the corresponding spectra of the intact glycans (as released by PNGase F) in providing structural information on N-glycans. 25132301 3 81 theme glycans 328:334 arg1 EndoH 302:306 EndoH 302:306 EndoH 302:306 EndoH or endoS release of glycans from glycoproteins, as used by many investigators, cleaves glycans between the GlcNAc residues of the chitobiose core leaving the glycan without the reducing-terminal GlcNAc residue. 25132301 3 81 theme glycans 328:334 arg1 release 317:323 endoS release 311:323 endoS release 311:323 EndoH or endoS release of glycans from glycoproteins, as used by many investigators, cleaves glycans between the GlcNAc residues of the chitobiose core leaving the glycan without the reducing-terminal GlcNAc residue. 25132301 11 82 theme endoS-released 1749:1762 arg1 glycans 1764:1770 endoH- and endoS-released glycans 1738:1770 endoH- and endoS-released glycans 1738:1770 CONCLUSIONS The results show that the CID spectra of endoH- and endoS-released glycans are as useful as the corresponding spectra of the intact glycans (as released by PNGase F) in providing structural information on N-glycans. 25132301 5 83 theme missing 713:719 arg1 GlcNAc 721:726 the missing GlcNAc 709:726 the missing GlcNAc 709:726 This paper examines the CID and ion mobility properties of these endoH-released glycans to determine if the missing GlcNAc influences the production of diagnostic fragment ions. 25132301 11 84 theme endoH- 1738:1743 arg1 glycans 1764:1770 endoH- and endoS-released glycans 1738:1770 endoH- and endoS-released glycans 1738:1770 CONCLUSIONS The results show that the CID spectra of endoH- and endoS-released glycans are as useful as the corresponding spectra of the intact glycans (as released by PNGase F) in providing structural information on N-glycans. 25132301 3 85 theme chitobiose 438:447 arg1 core 449:452 the chitobiose core 434:452 the chitobiose core leaving the glycan without the reducing-terminal GlcNAc residue 434:516 EndoH or endoS release of glycans from glycoproteins, as used by many investigators, cleaves glycans between the GlcNAc residues of the chitobiose core leaving the glycan without the reducing-terminal GlcNAc residue. 25132301 0 86 theme ions 26:29 arg1 Fragmentation 0:12 Fragmentation 0:12 Fragmentation of negative ions from N-linked carbohydrates: part 6. 0:66 Fragmentation of negative ions from N-linked carbohydrates: part 6. 25132301 5 87 theme ions 777:780 arg1 production 743:752 the production 739:752 the production of diagnostic fragment ions 739:780 This paper examines the CID and ion mobility properties of these endoH-released glycans to determine if the missing GlcNAc influences the production of diagnostic fragment ions. 25132301 3 88 theme GlcNAc 415:420 arg1 residues 422:429 the GlcNAc residues 411:429 the GlcNAc residues of the chitobiose core leaving the glycan without the reducing-terminal GlcNAc residue 411:516 EndoH or endoS release of glycans from glycoproteins, as used by many investigators, cleaves glycans between the GlcNAc residues of the chitobiose core leaving the glycan without the reducing-terminal GlcNAc residue. 25132301 3 88 theme GlcNAc 415:420 arg1 core 449:452 the chitobiose core 434:452 the chitobiose core leaving the glycan without the reducing-terminal GlcNAc residue 434:516 EndoH or endoS release of glycans from glycoproteins, as used by many investigators, cleaves glycans between the GlcNAc residues of the chitobiose core leaving the glycan without the reducing-terminal GlcNAc residue. 25132301 4 89 theme negative 534:541 arg1 spectra 551:557 their negative ion CID spectra 528:557 their negative ion CID spectra 528:557 However, their negative ion CID spectra do not appear to have been studied in detail. 25132301 2 90 theme CID 179:181 arg1 spectra 184:190 RATIONALE Negative ion collision-induced dissociation (CID) spectra 124:190 RATIONALE Negative ion collision-induced dissociation (CID) spectra of N-glycans 124:203 RATIONALE Negative ion collision-induced dissociation (CID) spectra of N-glycans contain many diagnostic ions that provide more structural information than positive ion spectra. 25132301 10 91 theme slight 1638:1643 arg1 adducts 1629:1635 chloride adducts 1620:1635 chloride adducts 1620:1635 The exception was the partial resolution of a pair of biantennary monogalactosylated glycans from IgG where, as chloride adducts, slight separation of the isomers was observed. 25132301 10 91 theme slight 1638:1643 arg1 separation 1645:1654 slight separation 1638:1654 slight separation of the isomers 1638:1669 The exception was the partial resolution of a pair of biantennary monogalactosylated glycans from IgG where, as chloride adducts, slight separation of the isomers was observed. 25132301 7 92 theme mass 1118:1121 arg1 spectrometer 1123:1134 a Waters Synapt G2 mass spectrometer 1099:1134 a Waters Synapt G2 mass spectrometer using nanospray sample introduction 1099:1170 Negative ion CID and travelling wave ion mobility spectra were recorded with a Waters Synapt G2 mass spectrometer using nanospray sample introduction. 25132301 9 93 theme ion 1362:1364 arg1 mobility 1366:1373 ion mobility 1362:1373 ion mobility 1362:1373 However, the ability of ion mobility to separate isomers was generally found to be inferior to its use with the full glycans despite the smaller nature of the compounds. 25132301 3 94 gly glycoproteins 341:353 arg1 glycoproteins 341:353 glycoproteins 341:353 glycoproteins 341:353 EndoH or endoS release of glycans from glycoproteins, as used by many investigators, cleaves glycans between the GlcNAc residues of the chitobiose core leaving the glycan without the reducing-terminal GlcNAc residue. 25132301 4 95 theme CID 547:549 arg1 spectra 551:557 their negative ion CID spectra 528:557 their negative ion CID spectra 528:557 However, their negative ion CID spectra do not appear to have been studied in detail. 25132301 2 96 theme many 213:216 arg1 ions 229:232 many diagnostic ions 213:232 many diagnostic ions that provide more structural information than positive ion spectra 213:299 RATIONALE Negative ion collision-induced dissociation (CID) spectra of N-glycans contain many diagnostic ions that provide more structural information than positive ion spectra. 25132301 3 97 theme GlcNAc 503:508 arg1 residue 510:516 the reducing-terminal GlcNAc residue 481:516 the reducing-terminal GlcNAc residue 481:516 EndoH or endoS release of glycans from glycoproteins, as used by many investigators, cleaves glycans between the GlcNAc residues of the chitobiose core leaving the glycan without the reducing-terminal GlcNAc residue. 25132301 2 98 theme N-glycans 195:203 arg1 spectra 184:190 RATIONALE Negative ion collision-induced dissociation (CID) spectra 124:190 RATIONALE Negative ion collision-induced dissociation (CID) spectra of N-glycans 124:203 RATIONALE Negative ion collision-induced dissociation (CID) spectra of N-glycans contain many diagnostic ions that provide more structural information than positive ion spectra. 25132301 10 99 theme isomers 1663:1669 arg1 adducts 1629:1635 chloride adducts 1620:1635 chloride adducts 1620:1635 The exception was the partial resolution of a pair of biantennary monogalactosylated glycans from IgG where, as chloride adducts, slight separation of the isomers was observed. 25132301 10 99 theme isomers 1663:1669 arg1 separation 1645:1654 slight separation 1638:1654 slight separation of the isomers 1638:1669 The exception was the partial resolution of a pair of biantennary monogalactosylated glycans from IgG where, as chloride adducts, slight separation of the isomers was observed. 25132301 2 100 theme RATIONALE 124:132 arg1 spectra 184:190 RATIONALE Negative ion collision-induced dissociation (CID) spectra 124:190 RATIONALE Negative ion collision-induced dissociation (CID) spectra of N-glycans 124:203 RATIONALE Negative ion collision-induced dissociation (CID) spectra of N-glycans contain many diagnostic ions that provide more structural information than positive ion spectra. 25132301 3 101 from release 317:323 arg1 glycoproteins 341:353 glycoproteins 341:353 glycoproteins 341:353 EndoH or endoS release of glycans from glycoproteins, as used by many investigators, cleaves glycans between the GlcNAc residues of the chitobiose core leaving the glycan without the reducing-terminal GlcNAc residue. 24816101 0 0 theme IIIA 96:99 arg1 pathology 61:69 the molecular pathology 47:69 the molecular pathology of mucopolysaccharidosis IIIA 47:99 Structure of sulfamidase provides insight into the molecular pathology of mucopolysaccharidosis IIIA. 24816101 5 1 theme unique 736:741 arg1 N-sulfatase 743:753 this unique N-sulfatase 731:753 this unique N-sulfatase 731:753 Despite the low sequence identity between this unique N-sulfatase and the group of O-sulfatases, they share a similar overall fold and active-site architecture, including a catalytic formylglycine, a divalent metal-binding site and a sulfate-binding site. 24816101 5 2 theme catalytic 862:870 arg1 site 912:915 a divalent metal-binding site 887:915 a divalent metal-binding site 887:915 Despite the low sequence identity between this unique N-sulfatase and the group of O-sulfatases, they share a similar overall fold and active-site architecture, including a catalytic formylglycine, a divalent metal-binding site and a sulfate-binding site. 24816101 5 2 theme catalytic 862:870 arg1 formylglycine 872:884 a catalytic formylglycine 860:884 a catalytic formylglycine 860:884 Despite the low sequence identity between this unique N-sulfatase and the group of O-sulfatases, they share a similar overall fold and active-site architecture, including a catalytic formylglycine, a divalent metal-binding site and a sulfate-binding site. 24816101 5 2 theme catalytic 862:870 arg1 site 939:942 a sulfate-binding site 921:942 a sulfate-binding site 921:942 Despite the low sequence identity between this unique N-sulfatase and the group of O-sulfatases, they share a similar overall fold and active-site architecture, including a catalytic formylglycine, a divalent metal-binding site and a sulfate-binding site. 24816101 0 3 theme mucopolysaccharidosis 74:94 arg1 IIIA 96:99 mucopolysaccharidosis IIIA 74:99 mucopolysaccharidosis IIIA 74:99 Structure of sulfamidase provides insight into the molecular pathology of mucopolysaccharidosis IIIA. 24816101 7 4 from function 1192:1199 arg1 IIIA 1231:1234 mucopolysaccharidosis type IIIA 1204:1234 mucopolysaccharidosis type IIIA 1204:1234 The structure also provides insight into the diverse effects of pathogenic mutations on SGSH function in mucopolysaccharidosis type IIIA and convincing evidence for the molecular consequences of many missense mutations. 24816101 1 5 theme fatal 161:165 arg1 disease 201:207 a fatal childhood-onset neurodegenerative disease 159:207 a fatal childhood-onset neurodegenerative disease with mild facial, visceral and skeletal abnormalities 159:261 Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome), a fatal childhood-onset neurodegenerative disease with mild facial, visceral and skeletal abnormalities, is caused by an inherited deficiency of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH; sulfamidase). 24816101 1 5 theme fatal 161:165 arg1 type 124:127 Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome) 102:156 Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome) 102:156 Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome), a fatal childhood-onset neurodegenerative disease with mild facial, visceral and skeletal abnormalities, is caused by an inherited deficiency of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH; sulfamidase). 24816101 6 6 theme conserved 963:971 arg1 lysine 973:978 a highly conserved lysine 954:978 a highly conserved lysine in O-sulfatases 954:994 However, a highly conserved lysine in O-sulfatases is replaced in SGSH by an arginine (Arg282) that is positioned to bind the N-linked sulfate substrate. 24816101 6 7 theme N-linked 1071:1078 arg1 substrate 1088:1096 the N-linked sulfate substrate 1067:1096 the N-linked sulfate substrate 1067:1096 However, a highly conserved lysine in O-sulfatases is replaced in SGSH by an arginine (Arg282) that is positioned to bind the N-linked sulfate substrate. 24816101 7 8 theme missense 1299:1306 arg1 mutations 1308:1316 many missense mutations 1294:1316 many missense mutations 1294:1316 The structure also provides insight into the diverse effects of pathogenic mutations on SGSH function in mucopolysaccharidosis type IIIA and convincing evidence for the molecular consequences of many missense mutations. 24816101 4 9 gly glycosylated 639:650 arg1 SGSH 652:655 glycosylated SGSH 639:655 glycosylated SGSH 639:655 Here, the crystal structure of glycosylated SGSH is presented at 2 Å resolution. 24816101 3 10 theme mutations 534:542 arg1 effect 518:523 the effect 514:523 the effect of these mutations 514:542 However, the molecular understanding of the effect of these mutations has been confined by a lack of structural data for this enzyme. 24816101 5 11 theme low 701:703 arg1 identity 714:721 the low sequence identity 697:721 the low sequence identity between this unique N-sulfatase and the group of O-sulfatases 697:783 Despite the low sequence identity between this unique N-sulfatase and the group of O-sulfatases, they share a similar overall fold and active-site architecture, including a catalytic formylglycine, a divalent metal-binding site and a sulfate-binding site. 24816101 5 12 theme sequence 705:712 arg1 identity 714:721 the low sequence identity 697:721 the low sequence identity between this unique N-sulfatase and the group of O-sulfatases 697:783 Despite the low sequence identity between this unique N-sulfatase and the group of O-sulfatases, they share a similar overall fold and active-site architecture, including a catalytic formylglycine, a divalent metal-binding site and a sulfate-binding site. 24816101 7 13 theme mucopolysaccharidosis 1204:1224 arg1 IIIA 1231:1234 mucopolysaccharidosis type IIIA 1204:1234 mucopolysaccharidosis type IIIA 1204:1234 The structure also provides insight into the diverse effects of pathogenic mutations on SGSH function in mucopolysaccharidosis type IIIA and convincing evidence for the molecular consequences of many missense mutations. 24816101 5 14 theme similar 799:805 arg1 fold 815:818 a similar overall fold 797:818 a similar overall fold 797:818 Despite the low sequence identity between this unique N-sulfatase and the group of O-sulfatases, they share a similar overall fold and active-site architecture, including a catalytic formylglycine, a divalent metal-binding site and a sulfate-binding site. 24816101 8 15 theme design 1445:1450 arg1 development 1409:1419 the development 1405:1419 the development of structure-based drug design 1405:1450 Further, the molecular characterization of SGSH mutations will lay the groundwork for the development of structure-based drug design for this devastating neurodegenerative disorder. 24816101 5 16 theme divalent 889:896 arg1 site 912:915 a divalent metal-binding site 887:915 a divalent metal-binding site 887:915 Despite the low sequence identity between this unique N-sulfatase and the group of O-sulfatases, they share a similar overall fold and active-site architecture, including a catalytic formylglycine, a divalent metal-binding site and a sulfate-binding site. 24816101 5 16 theme divalent 889:896 arg1 formylglycine 872:884 a catalytic formylglycine 860:884 a catalytic formylglycine 860:884 Despite the low sequence identity between this unique N-sulfatase and the group of O-sulfatases, they share a similar overall fold and active-site architecture, including a catalytic formylglycine, a divalent metal-binding site and a sulfate-binding site. 24816101 1 17 theme childhood-onset 167:181 arg1 disease 201:207 a fatal childhood-onset neurodegenerative disease 159:207 a fatal childhood-onset neurodegenerative disease with mild facial, visceral and skeletal abnormalities 159:261 Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome), a fatal childhood-onset neurodegenerative disease with mild facial, visceral and skeletal abnormalities, is caused by an inherited deficiency of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH; sulfamidase). 24816101 1 17 theme childhood-onset 167:181 arg1 type 124:127 Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome) 102:156 Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome) 102:156 Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome), a fatal childhood-onset neurodegenerative disease with mild facial, visceral and skeletal abnormalities, is caused by an inherited deficiency of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH; sulfamidase). 24816101 7 18 theme diverse 1144:1150 arg1 effects 1152:1158 the diverse effects 1140:1158 the diverse effects of pathogenic mutations on SGSH function in mucopolysaccharidosis type IIIA and convincing evidence for the molecular consequences of many missense mutations 1140:1316 The structure also provides insight into the diverse effects of pathogenic mutations on SGSH function in mucopolysaccharidosis type IIIA and convincing evidence for the molecular consequences of many missense mutations. 24816101 7 19 theme convincing 1240:1249 arg1 evidence 1251:1258 convincing evidence 1240:1258 convincing evidence for the molecular consequences of many missense mutations 1240:1316 The structure also provides insight into the diverse effects of pathogenic mutations on SGSH function in mucopolysaccharidosis type IIIA and convincing evidence for the molecular consequences of many missense mutations. 24816101 1 20 theme neurodegenerative 183:199 arg1 disease 201:207 a fatal childhood-onset neurodegenerative disease 159:207 a fatal childhood-onset neurodegenerative disease with mild facial, visceral and skeletal abnormalities 159:261 Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome), a fatal childhood-onset neurodegenerative disease with mild facial, visceral and skeletal abnormalities, is caused by an inherited deficiency of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH; sulfamidase). 24816101 1 20 theme neurodegenerative 183:199 arg1 type 124:127 Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome) 102:156 Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome) 102:156 Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome), a fatal childhood-onset neurodegenerative disease with mild facial, visceral and skeletal abnormalities, is caused by an inherited deficiency of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH; sulfamidase). 24816101 5 21 theme O-sulfatases 772:783 arg1 group 763:767 the group 759:767 the group of O-sulfatases 759:783 Despite the low sequence identity between this unique N-sulfatase and the group of O-sulfatases, they share a similar overall fold and active-site architecture, including a catalytic formylglycine, a divalent metal-binding site and a sulfate-binding site. 24816101 5 21 theme O-sulfatases 772:783 arg1 O-sulfatases 772:783 O-sulfatases 772:783 O-sulfatases 772:783 Despite the low sequence identity between this unique N-sulfatase and the group of O-sulfatases, they share a similar overall fold and active-site architecture, including a catalytic formylglycine, a divalent metal-binding site and a sulfate-binding site. 24816101 5 21 theme O-sulfatases 772:783 arg1 N-sulfatase 743:753 this unique N-sulfatase 731:753 this unique N-sulfatase 731:753 Despite the low sequence identity between this unique N-sulfatase and the group of O-sulfatases, they share a similar overall fold and active-site architecture, including a catalytic formylglycine, a divalent metal-binding site and a sulfate-binding site. 24816101 7 22 theme mutations 1174:1182 arg1 effects 1152:1158 the diverse effects 1140:1158 the diverse effects of pathogenic mutations on SGSH function in mucopolysaccharidosis type IIIA and convincing evidence for the molecular consequences of many missense mutations 1140:1316 The structure also provides insight into the diverse effects of pathogenic mutations on SGSH function in mucopolysaccharidosis type IIIA and convincing evidence for the molecular consequences of many missense mutations. 24816101 6 23 from lysine 973:978 arg1 O-sulfatases 983:994 O-sulfatases 983:994 O-sulfatases 983:994 However, a highly conserved lysine in O-sulfatases is replaced in SGSH by an arginine (Arg282) that is positioned to bind the N-linked sulfate substrate. 24816101 4 24 theme SGSH 652:655 arg1 structure 626:634 the crystal structure 614:634 the crystal structure of glycosylated SGSH 614:655 Here, the crystal structure of glycosylated SGSH is presented at 2 Å resolution. 24816101 1 25 theme inherited 280:288 arg1 deficiency 290:299 an inherited deficiency 277:299 an inherited deficiency of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH; sulfamidase) 277:367 Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome), a fatal childhood-onset neurodegenerative disease with mild facial, visceral and skeletal abnormalities, is caused by an inherited deficiency of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH; sulfamidase). 24816101 1 26 theme Mucopolysaccharidosis 102:122 arg1 disease 201:207 a fatal childhood-onset neurodegenerative disease 159:207 a fatal childhood-onset neurodegenerative disease with mild facial, visceral and skeletal abnormalities 159:261 Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome), a fatal childhood-onset neurodegenerative disease with mild facial, visceral and skeletal abnormalities, is caused by an inherited deficiency of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH; sulfamidase). 24816101 1 26 theme Mucopolysaccharidosis 102:122 arg1 type 124:127 Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome) 102:156 Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome) 102:156 Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome), a fatal childhood-onset neurodegenerative disease with mild facial, visceral and skeletal abnormalities, is caused by an inherited deficiency of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH; sulfamidase). 24816101 4 27 theme glycosylated 639:650 arg1 SGSH 652:655 glycosylated SGSH 639:655 glycosylated SGSH 639:655 Here, the crystal structure of glycosylated SGSH is presented at 2 Å resolution. 24816101 8 28 theme drug 1440:1443 arg1 design 1445:1450 structure-based drug design 1424:1450 structure-based drug design 1424:1450 Further, the molecular characterization of SGSH mutations will lay the groundwork for the development of structure-based drug design for this devastating neurodegenerative disorder. 24816101 7 29 from evidence 1251:1258 arg1 IIIA 1231:1234 mucopolysaccharidosis type IIIA 1204:1234 mucopolysaccharidosis type IIIA 1204:1234 The structure also provides insight into the diverse effects of pathogenic mutations on SGSH function in mucopolysaccharidosis type IIIA and convincing evidence for the molecular consequences of many missense mutations. 24816101 8 30 theme SGSH 1362:1365 arg1 mutations 1367:1375 SGSH mutations 1362:1375 SGSH mutations 1362:1375 Further, the molecular characterization of SGSH mutations will lay the groundwork for the development of structure-based drug design for this devastating neurodegenerative disorder. 24816101 1 31 theme mild 214:217 arg1 abnormalities 249:261 mild facial, visceral and skeletal abnormalities 214:261 mild facial, visceral and skeletal abnormalities 214:261 Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome), a fatal childhood-onset neurodegenerative disease with mild facial, visceral and skeletal abnormalities, is caused by an inherited deficiency of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH; sulfamidase). 24816101 0 32 theme sulfamidase 13:23 arg1 Structure 0:8 Structure 0:8 Structure of sulfamidase 0:23 Structure of sulfamidase provides insight into the molecular pathology of mucopolysaccharidosis IIIA. 24816101 1 33 dep SGSH 350:353 arg1 sulfamidase 356:366 sulfamidase 356:366 sulfamidase 356:366 Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome), a fatal childhood-onset neurodegenerative disease with mild facial, visceral and skeletal abnormalities, is caused by an inherited deficiency of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH; sulfamidase). 24816101 8 34 theme structure-based 1424:1438 arg1 design 1445:1450 structure-based drug design 1424:1450 structure-based drug design 1424:1450 Further, the molecular characterization of SGSH mutations will lay the groundwork for the development of structure-based drug design for this devastating neurodegenerative disorder. 24816101 5 35 theme sulfate-binding 923:937 arg1 formylglycine 872:884 a catalytic formylglycine 860:884 a catalytic formylglycine 860:884 Despite the low sequence identity between this unique N-sulfatase and the group of O-sulfatases, they share a similar overall fold and active-site architecture, including a catalytic formylglycine, a divalent metal-binding site and a sulfate-binding site. 24816101 5 35 theme sulfate-binding 923:937 arg1 site 939:942 a sulfate-binding site 921:942 a sulfate-binding site 921:942 Despite the low sequence identity between this unique N-sulfatase and the group of O-sulfatases, they share a similar overall fold and active-site architecture, including a catalytic formylglycine, a divalent metal-binding site and a sulfate-binding site. 24816101 1 36 theme facial 219:224 arg1 abnormalities 249:261 mild facial, visceral and skeletal abnormalities 214:261 mild facial, visceral and skeletal abnormalities 214:261 Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome), a fatal childhood-onset neurodegenerative disease with mild facial, visceral and skeletal abnormalities, is caused by an inherited deficiency of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH; sulfamidase). 24816101 3 37 theme molecular 487:495 arg1 understanding 497:509 the molecular understanding 483:509 the molecular understanding of the effect of these mutations 483:542 However, the molecular understanding of the effect of these mutations has been confined by a lack of structural data for this enzyme. 24816101 5 38 theme overall 807:813 arg1 fold 815:818 a similar overall fold 797:818 a similar overall fold 797:818 Despite the low sequence identity between this unique N-sulfatase and the group of O-sulfatases, they share a similar overall fold and active-site architecture, including a catalytic formylglycine, a divalent metal-binding site and a sulfate-binding site. 24816101 3 39 theme structural 575:584 arg1 data 586:589 structural data 575:589 structural data for this enzyme 575:605 However, the molecular understanding of the effect of these mutations has been confined by a lack of structural data for this enzyme. 24816101 7 40 theme many 1294:1297 arg1 mutations 1308:1316 many missense mutations 1294:1316 many missense mutations 1294:1316 The structure also provides insight into the diverse effects of pathogenic mutations on SGSH function in mucopolysaccharidosis type IIIA and convincing evidence for the molecular consequences of many missense mutations. 24816101 4 41 theme crystal 618:624 arg1 structure 626:634 the crystal structure 614:634 the crystal structure of glycosylated SGSH 614:655 Here, the crystal structure of glycosylated SGSH is presented at 2 Å resolution. 24816101 2 42 theme SGSH 401:404 arg1 gene 406:409 the SGSH gene 397:409 the SGSH gene 397:409 More than 100 mutations in the SGSH gene have been found to reduce or eliminate its enzymatic activity. 24816101 1 43 theme enzyme 308:313 arg1 SGSH 350:353 SGSH 350:353 SGSH 350:353 Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome), a fatal childhood-onset neurodegenerative disease with mild facial, visceral and skeletal abnormalities, is caused by an inherited deficiency of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH; sulfamidase). 24816101 1 43 theme enzyme 308:313 arg1 sulfohydrolase 334:347 the enzyme N-sulfoglucosamine sulfohydrolase 304:347 the enzyme N-sulfoglucosamine sulfohydrolase (SGSH; sulfamidase) 304:367 Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome), a fatal childhood-onset neurodegenerative disease with mild facial, visceral and skeletal abnormalities, is caused by an inherited deficiency of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH; sulfamidase). 24816101 7 44 from effects 1152:1158 arg1 function 1192:1199 SGSH function 1187:1199 SGSH function in mucopolysaccharidosis type IIIA 1187:1234 The structure also provides insight into the diverse effects of pathogenic mutations on SGSH function in mucopolysaccharidosis type IIIA and convincing evidence for the molecular consequences of many missense mutations. 24816101 7 44 from effects 1152:1158 arg1 evidence 1251:1258 convincing evidence 1240:1258 convincing evidence for the molecular consequences of many missense mutations 1240:1316 The structure also provides insight into the diverse effects of pathogenic mutations on SGSH function in mucopolysaccharidosis type IIIA and convincing evidence for the molecular consequences of many missense mutations. 24816101 3 45 theme data 586:589 arg1 lack 567:570 a lack 565:570 a lack of structural data for this enzyme 565:605 However, the molecular understanding of the effect of these mutations has been confined by a lack of structural data for this enzyme. 24816101 1 46 theme visceral 227:234 arg1 abnormalities 249:261 mild facial, visceral and skeletal abnormalities 214:261 mild facial, visceral and skeletal abnormalities 214:261 Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome), a fatal childhood-onset neurodegenerative disease with mild facial, visceral and skeletal abnormalities, is caused by an inherited deficiency of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH; sulfamidase). 24816101 0 47 theme molecular 51:59 arg1 pathology 61:69 the molecular pathology 47:69 the molecular pathology of mucopolysaccharidosis IIIA 47:99 Structure of sulfamidase provides insight into the molecular pathology of mucopolysaccharidosis IIIA. 24816101 1 48 theme N-sulfoglucosamine 315:332 arg1 SGSH 350:353 SGSH 350:353 SGSH 350:353 Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome), a fatal childhood-onset neurodegenerative disease with mild facial, visceral and skeletal abnormalities, is caused by an inherited deficiency of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH; sulfamidase). 24816101 1 48 theme N-sulfoglucosamine 315:332 arg1 sulfohydrolase 334:347 the enzyme N-sulfoglucosamine sulfohydrolase 304:347 the enzyme N-sulfoglucosamine sulfohydrolase (SGSH; sulfamidase) 304:367 Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome), a fatal childhood-onset neurodegenerative disease with mild facial, visceral and skeletal abnormalities, is caused by an inherited deficiency of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH; sulfamidase). 24816101 1 49 with disease 201:207 arg1 abnormalities 249:261 mild facial, visceral and skeletal abnormalities 214:261 mild facial, visceral and skeletal abnormalities 214:261 Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome), a fatal childhood-onset neurodegenerative disease with mild facial, visceral and skeletal abnormalities, is caused by an inherited deficiency of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH; sulfamidase). 24816101 6 50 link N-linked 1071:1078 arg1 substrate 1088:1096 the N-linked sulfate substrate 1067:1096 the N-linked sulfate substrate 1067:1096 However, a highly conserved lysine in O-sulfatases is replaced in SGSH by an arginine (Arg282) that is positioned to bind the N-linked sulfate substrate. 24816101 2 51 from mutations 384:392 arg1 gene 406:409 the SGSH gene 397:409 the SGSH gene 397:409 More than 100 mutations in the SGSH gene have been found to reduce or eliminate its enzymatic activity. 24816101 6 52 theme sulfate 1080:1086 arg1 substrate 1088:1096 the N-linked sulfate substrate 1067:1096 the N-linked sulfate substrate 1067:1096 However, a highly conserved lysine in O-sulfatases is replaced in SGSH by an arginine (Arg282) that is positioned to bind the N-linked sulfate substrate. 24816101 1 53 theme sulfohydrolase 334:347 arg1 deficiency 290:299 an inherited deficiency 277:299 an inherited deficiency of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH; sulfamidase) 277:367 Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome), a fatal childhood-onset neurodegenerative disease with mild facial, visceral and skeletal abnormalities, is caused by an inherited deficiency of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH; sulfamidase). 24816101 7 54 theme mutations 1308:1316 arg1 consequences 1278:1289 the molecular consequences 1264:1289 the molecular consequences of many missense mutations 1264:1316 The structure also provides insight into the diverse effects of pathogenic mutations on SGSH function in mucopolysaccharidosis type IIIA and convincing evidence for the molecular consequences of many missense mutations. 24816101 1 55 theme Sanfilippo 135:144 arg1 syndrome 148:155 Sanfilippo A syndrome 135:155 Sanfilippo A syndrome 135:155 Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome), a fatal childhood-onset neurodegenerative disease with mild facial, visceral and skeletal abnormalities, is caused by an inherited deficiency of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH; sulfamidase). 24816101 1 55 theme Sanfilippo 135:144 arg1 IIIA 129:132 IIIA 129:132 Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome) 102:156 Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome), a fatal childhood-onset neurodegenerative disease with mild facial, visceral and skeletal abnormalities, is caused by an inherited deficiency of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH; sulfamidase). 24816101 7 56 theme type 1226:1229 arg1 IIIA 1231:1234 mucopolysaccharidosis type IIIA 1204:1234 mucopolysaccharidosis type IIIA 1204:1234 The structure also provides insight into the diverse effects of pathogenic mutations on SGSH function in mucopolysaccharidosis type IIIA and convincing evidence for the molecular consequences of many missense mutations. 24816101 8 57 theme molecular 1332:1340 arg1 characterization 1342:1357 the molecular characterization 1328:1357 the molecular characterization of SGSH mutations 1328:1375 Further, the molecular characterization of SGSH mutations will lay the groundwork for the development of structure-based drug design for this devastating neurodegenerative disorder. 24816101 8 58 theme mutations 1367:1375 arg1 characterization 1342:1357 the molecular characterization 1328:1357 the molecular characterization of SGSH mutations 1328:1375 Further, the molecular characterization of SGSH mutations will lay the groundwork for the development of structure-based drug design for this devastating neurodegenerative disorder. 24816101 1 59 theme A 146:146 arg1 syndrome 148:155 Sanfilippo A syndrome 135:155 Sanfilippo A syndrome 135:155 Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome), a fatal childhood-onset neurodegenerative disease with mild facial, visceral and skeletal abnormalities, is caused by an inherited deficiency of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH; sulfamidase). 24816101 1 59 theme A 146:146 arg1 IIIA 129:132 IIIA 129:132 Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome) 102:156 Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome), a fatal childhood-onset neurodegenerative disease with mild facial, visceral and skeletal abnormalities, is caused by an inherited deficiency of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH; sulfamidase). 24816101 7 60 theme pathogenic 1163:1172 arg1 mutations 1174:1182 pathogenic mutations 1163:1182 pathogenic mutations 1163:1182 The structure also provides insight into the diverse effects of pathogenic mutations on SGSH function in mucopolysaccharidosis type IIIA and convincing evidence for the molecular consequences of many missense mutations. 24816101 8 61 theme neurodegenerative 1473:1489 arg1 disorder 1491:1498 this devastating neurodegenerative disorder 1456:1498 this devastating neurodegenerative disorder 1456:1498 Further, the molecular characterization of SGSH mutations will lay the groundwork for the development of structure-based drug design for this devastating neurodegenerative disorder. 24816101 5 62 theme metal-binding 898:910 arg1 site 912:915 a divalent metal-binding site 887:915 a divalent metal-binding site 887:915 Despite the low sequence identity between this unique N-sulfatase and the group of O-sulfatases, they share a similar overall fold and active-site architecture, including a catalytic formylglycine, a divalent metal-binding site and a sulfate-binding site. 24816101 5 62 theme metal-binding 898:910 arg1 formylglycine 872:884 a catalytic formylglycine 860:884 a catalytic formylglycine 860:884 Despite the low sequence identity between this unique N-sulfatase and the group of O-sulfatases, they share a similar overall fold and active-site architecture, including a catalytic formylglycine, a divalent metal-binding site and a sulfate-binding site. 24816101 1 63 theme skeletal 240:247 arg1 abnormalities 249:261 mild facial, visceral and skeletal abnormalities 214:261 mild facial, visceral and skeletal abnormalities 214:261 Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome), a fatal childhood-onset neurodegenerative disease with mild facial, visceral and skeletal abnormalities, is caused by an inherited deficiency of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH; sulfamidase). 24816101 7 64 theme SGSH 1187:1190 arg1 function 1192:1199 SGSH function 1187:1199 SGSH function in mucopolysaccharidosis type IIIA 1187:1234 The structure also provides insight into the diverse effects of pathogenic mutations on SGSH function in mucopolysaccharidosis type IIIA and convincing evidence for the molecular consequences of many missense mutations. 24816101 8 65 theme devastating 1461:1471 arg1 disorder 1491:1498 this devastating neurodegenerative disorder 1456:1498 this devastating neurodegenerative disorder 1456:1498 Further, the molecular characterization of SGSH mutations will lay the groundwork for the development of structure-based drug design for this devastating neurodegenerative disorder. 24816101 7 66 theme molecular 1268:1276 arg1 consequences 1278:1289 the molecular consequences 1264:1289 the molecular consequences of many missense mutations 1264:1316 The structure also provides insight into the diverse effects of pathogenic mutations on SGSH function in mucopolysaccharidosis type IIIA and convincing evidence for the molecular consequences of many missense mutations. 24816101 1 67 dep type 124:127 arg1 syndrome 148:155 Sanfilippo A syndrome 135:155 Sanfilippo A syndrome 135:155 Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome), a fatal childhood-onset neurodegenerative disease with mild facial, visceral and skeletal abnormalities, is caused by an inherited deficiency of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH; sulfamidase). 24816101 1 67 dep type 124:127 arg1 IIIA 129:132 IIIA 129:132 Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome) 102:156 Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome), a fatal childhood-onset neurodegenerative disease with mild facial, visceral and skeletal abnormalities, is caused by an inherited deficiency of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH; sulfamidase). 24816101 5 68 theme active-site 824:834 arg1 architecture 836:847 active-site architecture 824:847 active-site architecture 824:847 Despite the low sequence identity between this unique N-sulfatase and the group of O-sulfatases, they share a similar overall fold and active-site architecture, including a catalytic formylglycine, a divalent metal-binding site and a sulfate-binding site. 24816101 2 69 theme enzymatic 454:462 arg1 activity 464:471 its enzymatic activity 450:471 its enzymatic activity 450:471 More than 100 mutations in the SGSH gene have been found to reduce or eliminate its enzymatic activity. 24816101 3 70 theme effect 518:523 arg1 understanding 497:509 the molecular understanding 483:509 the molecular understanding of the effect of these mutations 483:542 However, the molecular understanding of the effect of these mutations has been confined by a lack of structural data for this enzyme. 24816101 4 71 theme Å 675:675 arg1 resolution 677:686 2 Å resolution 673:686 2 Å resolution 673:686 Here, the crystal structure of glycosylated SGSH is presented at 2 Å resolution. 24696276 0 0 from characterization 19:34 arg1 cantonensis 89:99 Angiostrongylus cantonensis 73:99 Angiostrongylus cantonensis 73:99 Identification and characterization of an asparaginyl endopeptidase from Angiostrongylus cantonensis. 24696276 7 1 theme recombinant 971:981 arg1 enzyme 983:988 this recombinant enzyme 966:988 this recombinant enzyme 966:988 Posttranslational modification was shown to occur via N-linked glycosylation in this recombinant enzyme. 24696276 4 2 theme acid 547:550 arg1 sequences 552:560 the amino acid sequences 537:560 the amino acid sequences of the asparaginyl endopeptidases of other parasitic helminths 537:623 This putative protein was determined to have 37-65% identity in the amino acid sequences of the asparaginyl endopeptidases of other parasitic helminths. 24696276 5 3 theme real-time 629:637 arg1 analysis 656:663 real-time quantitative PCR analysis 629:663 real-time quantitative PCR analysis 629:663 By real-time quantitative PCR analysis, Ac-AEP was revealed to be more abundantly expressed in the female adult worms than in other development stages. 24696276 6 4 theme asparaginyl 792:802 arg1 rAc-AEP 819:825 rAc-AEP 819:825 rAc-AEP 819:825 A recombinant asparaginyl endopeptidase (rAc-AEP) was then produced by a Pichia pastoris expression system. 24696276 6 4 theme asparaginyl 792:802 arg1 endopeptidase 804:816 A recombinant asparaginyl endopeptidase 778:816 A recombinant asparaginyl endopeptidase (rAc-AEP) 778:826 A recombinant asparaginyl endopeptidase (rAc-AEP) was then produced by a Pichia pastoris expression system. 24696276 1 5 theme cysteine 168:175 arg1 proteases 177:185 cysteine proteases 168:185 cysteine proteases in many organisms 168:203 Asparaginyl endopeptidase, also known as legumain, is a family of cysteine proteases in many organisms. 24696276 4 6 theme amino 541:545 arg1 sequences 552:560 the amino acid sequences 537:560 the amino acid sequences of the asparaginyl endopeptidases of other parasitic helminths 537:623 This putative protein was determined to have 37-65% identity in the amino acid sequences of the asparaginyl endopeptidases of other parasitic helminths. 24696276 0 7 from Identification 0:13 arg1 cantonensis 89:99 Angiostrongylus cantonensis 73:99 Angiostrongylus cantonensis 73:99 Identification and characterization of an asparaginyl endopeptidase from Angiostrongylus cantonensis. 24696276 5 8 theme quantitative 639:650 arg1 analysis 656:663 real-time quantitative PCR analysis 629:663 real-time quantitative PCR analysis 629:663 By real-time quantitative PCR analysis, Ac-AEP was revealed to be more abundantly expressed in the female adult worms than in other development stages. 24696276 6 9 theme recombinant 780:790 arg1 rAc-AEP 819:825 rAc-AEP 819:825 rAc-AEP 819:825 A recombinant asparaginyl endopeptidase (rAc-AEP) was then produced by a Pichia pastoris expression system. 24696276 6 9 theme recombinant 780:790 arg1 endopeptidase 804:816 A recombinant asparaginyl endopeptidase 778:816 A recombinant asparaginyl endopeptidase (rAc-AEP) 778:826 A recombinant asparaginyl endopeptidase (rAc-AEP) was then produced by a Pichia pastoris expression system. 24696276 2 10 theme cDNA 283:286 arg1 library 288:294 the cDNA library 279:294 the cDNA library of Angiostrongylus cantonensis 279:325 In this study, an asparaginyl endopeptidase (Ac-AEP) was identified from the cDNA library of Angiostrongylus cantonensis. 24696276 9 11 with patients 1240:1247 arg1 meningitis 1267:1276 eosinophilic meningitis 1254:1276 eosinophilic meningitis 1254:1276 Moreover, the purified rAc-AEP was recognized by IgG in serum samples from BALB/c or ICR mice with A. cantonensis infection and patients with eosinophilic meningitis. 24696276 9 11 with patients 1240:1247 arg1 infection 1226:1234 A. cantonensis infection 1211:1234 A. cantonensis infection 1211:1234 Moreover, the purified rAc-AEP was recognized by IgG in serum samples from BALB/c or ICR mice with A. cantonensis infection and patients with eosinophilic meningitis. 24696276 9 12 theme eosinophilic 1254:1265 arg1 meningitis 1267:1276 eosinophilic meningitis 1254:1276 eosinophilic meningitis 1254:1276 Moreover, the purified rAc-AEP was recognized by IgG in serum samples from BALB/c or ICR mice with A. cantonensis infection and patients with eosinophilic meningitis. 24696276 9 13 from mice 1201:1204 arg1 samples 1174:1180 serum samples 1168:1180 serum samples from BALB/c or ICR mice with A. cantonensis infection and patients with eosinophilic meningitis 1168:1276 Moreover, the purified rAc-AEP was recognized by IgG in serum samples from BALB/c or ICR mice with A. cantonensis infection and patients with eosinophilic meningitis. 24696276 6 14 theme expression 867:876 arg1 system 878:883 a Pichia pastoris expression system 849:883 a Pichia pastoris expression system 849:883 A recombinant asparaginyl endopeptidase (rAc-AEP) was then produced by a Pichia pastoris expression system. 24696276 5 15 theme PCR 652:654 arg1 analysis 656:663 real-time quantitative PCR analysis 629:663 real-time quantitative PCR analysis 629:663 By real-time quantitative PCR analysis, Ac-AEP was revealed to be more abundantly expressed in the female adult worms than in other development stages. 24696276 10 16 dep A. 1357:1358 arg1 cantonensis 1360:1370 cantonensis 1360:1370 cantonensis 1360:1370 These findings indicate that the rAc-AEP may have the potential for detecting A. cantonensis infection. 24696276 3 17 theme Ac-AEP 347:352 arg1 full-length 332:342 The full-length 328:342 The full-length of Ac-AEP 328:352 The full-length of Ac-AEP was determined to be 1,472 bp with an open reading frame of 1,341 bp encoding a putative protein with 446 amino acids. 24696276 3 17 theme Ac-AEP 347:352 arg1 bp 381:382 1,472 bp 375:382 1,472 bp 375:382 The full-length of Ac-AEP was determined to be 1,472 bp with an open reading frame of 1,341 bp encoding a putative protein with 446 amino acids. 24696276 6 18 theme pastoris 858:865 arg1 system 878:883 a Pichia pastoris expression system 849:883 a Pichia pastoris expression system 849:883 A recombinant asparaginyl endopeptidase (rAc-AEP) was then produced by a Pichia pastoris expression system. 24696276 1 19 from family 158:163 arg1 organisms 195:203 many organisms 190:203 many organisms 190:203 Asparaginyl endopeptidase, also known as legumain, is a family of cysteine proteases in many organisms. 24696276 1 20 theme proteases 177:185 arg1 family 158:163 a family 156:163 a family of cysteine proteases in many organisms 156:203 Asparaginyl endopeptidase, also known as legumain, is a family of cysteine proteases in many organisms. 24696276 1 20 theme proteases 177:185 arg1 endopeptidase 114:126 Asparaginyl endopeptidase 102:126 Asparaginyl endopeptidase 102:126 Asparaginyl endopeptidase, also known as legumain, is a family of cysteine proteases in many organisms. 24696276 0 21 theme endopeptidase 54:66 arg1 characterization 19:34 characterization 19:34 characterization 19:34 Identification and characterization of an asparaginyl endopeptidase from Angiostrongylus cantonensis. 24696276 0 21 theme endopeptidase 54:66 arg1 Identification 0:13 Identification 0:13 Identification 0:13 Identification and characterization of an asparaginyl endopeptidase from Angiostrongylus cantonensis. 24696276 6 22 theme Pichia 851:856 arg1 system 878:883 a Pichia pastoris expression system 849:883 a Pichia pastoris expression system 849:883 A recombinant asparaginyl endopeptidase (rAc-AEP) was then produced by a Pichia pastoris expression system. 24696276 0 23 theme asparaginyl 42:52 arg1 endopeptidase 54:66 an asparaginyl endopeptidase 39:66 an asparaginyl endopeptidase from Angiostrongylus cantonensis 39:99 Identification and characterization of an asparaginyl endopeptidase from Angiostrongylus cantonensis. 24696276 8 24 theme proteolytic 995:1005 arg1 activity 1007:1014 The proteolytic activity 991:1014 The proteolytic activity of rAc-AEP 991:1025 The proteolytic activity of rAc-AEP was inhibited by iodoacetamide but not affected by E64, pepatain A, AEBSF, and EDTA. 24696276 1 25 theme Asparaginyl 102:112 arg1 family 158:163 a family 156:163 a family of cysteine proteases in many organisms 156:203 Asparaginyl endopeptidase, also known as legumain, is a family of cysteine proteases in many organisms. 24696276 1 25 theme Asparaginyl 102:112 arg1 endopeptidase 114:126 Asparaginyl endopeptidase 102:126 Asparaginyl endopeptidase 102:126 Asparaginyl endopeptidase, also known as legumain, is a family of cysteine proteases in many organisms. 24696276 9 26 theme serum 1168:1172 arg1 samples 1174:1180 serum samples 1168:1180 serum samples from BALB/c or ICR mice with A. cantonensis infection and patients with eosinophilic meningitis 1168:1276 Moreover, the purified rAc-AEP was recognized by IgG in serum samples from BALB/c or ICR mice with A. cantonensis infection and patients with eosinophilic meningitis. 24696276 2 27 theme cantonensis 315:325 arg1 library 288:294 the cDNA library 279:294 the cDNA library of Angiostrongylus cantonensis 279:325 In this study, an asparaginyl endopeptidase (Ac-AEP) was identified from the cDNA library of Angiostrongylus cantonensis. 24696276 1 28 theme many 190:193 arg1 organisms 195:203 many organisms 190:203 many organisms 190:203 Asparaginyl endopeptidase, also known as legumain, is a family of cysteine proteases in many organisms. 24696276 8 29 theme pepatain 1083:1090 arg1 A 1092:1092 pepatain A 1083:1092 pepatain A 1083:1092 The proteolytic activity of rAc-AEP was inhibited by iodoacetamide but not affected by E64, pepatain A, AEBSF, and EDTA. 24696276 2 30 theme Angiostrongylus 299:313 arg1 cantonensis 315:325 Angiostrongylus cantonensis 299:325 Angiostrongylus cantonensis 299:325 In this study, an asparaginyl endopeptidase (Ac-AEP) was identified from the cDNA library of Angiostrongylus cantonensis. 24696276 8 31 theme rAc-AEP 1019:1025 arg1 activity 1007:1014 The proteolytic activity 991:1014 The proteolytic activity of rAc-AEP 991:1025 The proteolytic activity of rAc-AEP was inhibited by iodoacetamide but not affected by E64, pepatain A, AEBSF, and EDTA. 24696276 4 32 theme % 523:523 arg1 identity 525:532 37-65% identity 518:532 37-65% identity 518:532 This putative protein was determined to have 37-65% identity in the amino acid sequences of the asparaginyl endopeptidases of other parasitic helminths. 24696276 7 33 theme N-linked 940:947 arg1 glycosylation 949:961 N-linked glycosylation 940:961 N-linked glycosylation 940:961 Posttranslational modification was shown to occur via N-linked glycosylation in this recombinant enzyme. 24696276 3 34 with bp 381:382 arg1 frame 405:409 an open reading frame 389:409 an open reading frame of 1,341 bp encoding a putative protein with 446 amino acids 389:470 The full-length of Ac-AEP was determined to be 1,472 bp with an open reading frame of 1,341 bp encoding a putative protein with 446 amino acids. 24696276 9 35 with mice 1201:1204 arg1 meningitis 1267:1276 eosinophilic meningitis 1254:1276 eosinophilic meningitis 1254:1276 Moreover, the purified rAc-AEP was recognized by IgG in serum samples from BALB/c or ICR mice with A. cantonensis infection and patients with eosinophilic meningitis. 24696276 9 35 with mice 1201:1204 arg1 infection 1226:1234 A. cantonensis infection 1211:1234 A. cantonensis infection 1211:1234 Moreover, the purified rAc-AEP was recognized by IgG in serum samples from BALB/c or ICR mice with A. cantonensis infection and patients with eosinophilic meningitis. 24696276 4 36 theme parasitic 605:613 arg1 helminths 615:623 other parasitic helminths 599:623 other parasitic helminths 599:623 This putative protein was determined to have 37-65% identity in the amino acid sequences of the asparaginyl endopeptidases of other parasitic helminths. 24696276 9 37 theme BALB/c 1187:1192 arg1 mice 1201:1204 BALB/c or ICR mice 1187:1204 mice 1201:1204 Moreover, the purified rAc-AEP was recognized by IgG in serum samples from BALB/c or ICR mice with A. cantonensis infection and patients with eosinophilic meningitis. 24696276 4 38 theme other 599:603 arg1 helminths 615:623 other parasitic helminths 599:623 other parasitic helminths 599:623 This putative protein was determined to have 37-65% identity in the amino acid sequences of the asparaginyl endopeptidases of other parasitic helminths. 24696276 3 39 theme reading 397:403 arg1 frame 405:409 an open reading frame 389:409 an open reading frame of 1,341 bp encoding a putative protein with 446 amino acids 389:470 The full-length of Ac-AEP was determined to be 1,472 bp with an open reading frame of 1,341 bp encoding a putative protein with 446 amino acids. 24696276 3 40 with protein 443:449 arg1 acids 466:470 446 amino acids 456:470 446 amino acids 456:470 The full-length of Ac-AEP was determined to be 1,472 bp with an open reading frame of 1,341 bp encoding a putative protein with 446 amino acids. 24696276 3 41 theme bp 420:421 arg1 frame 405:409 an open reading frame 389:409 an open reading frame of 1,341 bp encoding a putative protein with 446 amino acids 389:470 The full-length of Ac-AEP was determined to be 1,472 bp with an open reading frame of 1,341 bp encoding a putative protein with 446 amino acids. 24696276 5 42 theme other 752:756 arg1 stages 770:775 other development stages 752:775 other development stages 752:775 By real-time quantitative PCR analysis, Ac-AEP was revealed to be more abundantly expressed in the female adult worms than in other development stages. 24696276 0 43 from cantonensis 89:99 arg1 characterization 19:34 characterization 19:34 characterization 19:34 Identification and characterization of an asparaginyl endopeptidase from Angiostrongylus cantonensis. 24696276 0 43 from cantonensis 89:99 arg1 Identification 0:13 Identification 0:13 Identification 0:13 Identification and characterization of an asparaginyl endopeptidase from Angiostrongylus cantonensis. 24696276 0 43 from cantonensis 89:99 arg1 endopeptidase 54:66 an asparaginyl endopeptidase 39:66 an asparaginyl endopeptidase from Angiostrongylus cantonensis 39:99 Identification and characterization of an asparaginyl endopeptidase from Angiostrongylus cantonensis. 24696276 2 44 theme asparaginyl 224:234 arg1 Ac-AEP 251:256 Ac-AEP 251:256 Ac-AEP 251:256 In this study, an asparaginyl endopeptidase (Ac-AEP) was identified from the cDNA library of Angiostrongylus cantonensis. 24696276 2 44 theme asparaginyl 224:234 arg1 endopeptidase 236:248 an asparaginyl endopeptidase 221:248 an asparaginyl endopeptidase (Ac-AEP) 221:257 In this study, an asparaginyl endopeptidase (Ac-AEP) was identified from the cDNA library of Angiostrongylus cantonensis. 24696276 3 45 theme putative 434:441 arg1 protein 443:449 a putative protein 432:449 a putative protein with 446 amino acids 432:470 The full-length of Ac-AEP was determined to be 1,472 bp with an open reading frame of 1,341 bp encoding a putative protein with 446 amino acids. 24696276 5 46 theme development 758:768 arg1 stages 770:775 other development stages 752:775 other development stages 752:775 By real-time quantitative PCR analysis, Ac-AEP was revealed to be more abundantly expressed in the female adult worms than in other development stages. 24696276 10 47 contain have 1324:1327 arg2 potential 1333:1341 the potential 1329:1341 the potential for detecting A. cantonensis infection 1329:1380 These findings indicate that the rAc-AEP may have the potential for detecting A. cantonensis infection. 24696276 10 47 contain have 1324:1327 arg1 rAc-AEP 1312:1318 the rAc-AEP 1308:1318 the rAc-AEP 1308:1318 These findings indicate that the rAc-AEP may have the potential for detecting A. cantonensis infection. 24696276 5 48 theme adult 732:736 arg1 worms 738:742 the female adult worms 721:742 the female adult worms 721:742 By real-time quantitative PCR analysis, Ac-AEP was revealed to be more abundantly expressed in the female adult worms than in other development stages. 24696276 3 49 theme open 392:395 arg1 frame 405:409 an open reading frame 389:409 an open reading frame of 1,341 bp encoding a putative protein with 446 amino acids 389:470 The full-length of Ac-AEP was determined to be 1,472 bp with an open reading frame of 1,341 bp encoding a putative protein with 446 amino acids. 24696276 4 50 theme 37-65 518:522 arg1 % 523:523 % 523:523 % 523:523 This putative protein was determined to have 37-65% identity in the amino acid sequences of the asparaginyl endopeptidases of other parasitic helminths. 24696276 9 51 theme ICR 1197:1199 arg1 mice 1201:1204 BALB/c or ICR mice 1187:1204 mice 1201:1204 Moreover, the purified rAc-AEP was recognized by IgG in serum samples from BALB/c or ICR mice with A. cantonensis infection and patients with eosinophilic meningitis. 24696276 7 52 theme Posttranslational 886:902 arg1 modification 904:915 Posttranslational modification 886:915 Posttranslational modification 886:915 Posttranslational modification was shown to occur via N-linked glycosylation in this recombinant enzyme. 24696276 9 53 theme A. 1211:1212 arg1 infection 1226:1234 A. cantonensis infection 1211:1234 A. cantonensis infection 1211:1234 Moreover, the purified rAc-AEP was recognized by IgG in serum samples from BALB/c or ICR mice with A. cantonensis infection and patients with eosinophilic meningitis. 24696276 10 54 theme A. 1357:1358 arg1 infection 1372:1380 A. cantonensis infection 1357:1380 A. cantonensis infection 1357:1380 These findings indicate that the rAc-AEP may have the potential for detecting A. cantonensis infection. 24696276 9 55 theme purified 1126:1133 arg1 rAc-AEP 1135:1141 the purified rAc-AEP 1122:1141 the purified rAc-AEP 1122:1141 Moreover, the purified rAc-AEP was recognized by IgG in serum samples from BALB/c or ICR mice with A. cantonensis infection and patients with eosinophilic meningitis. 24696276 4 56 theme asparaginyl 569:579 arg1 endopeptidases 581:594 the asparaginyl endopeptidases 565:594 the asparaginyl endopeptidases of other parasitic helminths 565:623 This putative protein was determined to have 37-65% identity in the amino acid sequences of the asparaginyl endopeptidases of other parasitic helminths. 24696276 9 57 theme cantonensis 1214:1224 arg1 infection 1226:1234 A. cantonensis infection 1211:1234 A. cantonensis infection 1211:1234 Moreover, the purified rAc-AEP was recognized by IgG in serum samples from BALB/c or ICR mice with A. cantonensis infection and patients with eosinophilic meningitis. 24696276 4 58 contain have 513:516 arg2 identity 525:532 37-65% identity 518:532 37-65% identity 518:532 This putative protein was determined to have 37-65% identity in the amino acid sequences of the asparaginyl endopeptidases of other parasitic helminths. 24696276 4 58 contain have 513:516 arg1 protein 487:493 This putative protein 473:493 This putative protein 473:493 This putative protein was determined to have 37-65% identity in the amino acid sequences of the asparaginyl endopeptidases of other parasitic helminths. 24696276 3 59 theme amino 460:464 arg1 acids 466:470 446 amino acids 456:470 446 amino acids 456:470 The full-length of Ac-AEP was determined to be 1,472 bp with an open reading frame of 1,341 bp encoding a putative protein with 446 amino acids. 24696276 5 60 theme female 725:730 arg1 worms 738:742 the female adult worms 721:742 the female adult worms 721:742 By real-time quantitative PCR analysis, Ac-AEP was revealed to be more abundantly expressed in the female adult worms than in other development stages. 24696276 4 61 theme helminths 615:623 arg1 endopeptidases 581:594 the asparaginyl endopeptidases 565:594 the asparaginyl endopeptidases of other parasitic helminths 565:623 This putative protein was determined to have 37-65% identity in the amino acid sequences of the asparaginyl endopeptidases of other parasitic helminths. 24696276 9 62 from patients 1240:1247 arg1 samples 1174:1180 serum samples 1168:1180 serum samples from BALB/c or ICR mice with A. cantonensis infection and patients with eosinophilic meningitis 1168:1276 Moreover, the purified rAc-AEP was recognized by IgG in serum samples from BALB/c or ICR mice with A. cantonensis infection and patients with eosinophilic meningitis. 24696276 1 63 from organisms 195:203 arg1 family 158:163 a family 156:163 a family of cysteine proteases in many organisms 156:203 Asparaginyl endopeptidase, also known as legumain, is a family of cysteine proteases in many organisms. 24696276 1 63 from organisms 195:203 arg1 endopeptidase 114:126 Asparaginyl endopeptidase 102:126 Asparaginyl endopeptidase 102:126 Asparaginyl endopeptidase, also known as legumain, is a family of cysteine proteases in many organisms. 24696276 7 64 link N-linked 940:947 arg1 glycosylation 949:961 N-linked glycosylation 940:961 N-linked glycosylation 940:961 Posttranslational modification was shown to occur via N-linked glycosylation in this recombinant enzyme. 24696276 0 65 theme Angiostrongylus 73:87 arg1 cantonensis 89:99 Angiostrongylus cantonensis 73:99 Angiostrongylus cantonensis 73:99 Identification and characterization of an asparaginyl endopeptidase from Angiostrongylus cantonensis. 24696276 4 66 theme putative 478:485 arg1 protein 487:493 This putative protein 473:493 This putative protein 473:493 This putative protein was determined to have 37-65% identity in the amino acid sequences of the asparaginyl endopeptidases of other parasitic helminths. 24696276 1 67 from proteases 177:185 arg1 organisms 195:203 many organisms 190:203 many organisms 190:203 Asparaginyl endopeptidase, also known as legumain, is a family of cysteine proteases in many organisms. 24696276 4 68 theme endopeptidases 581:594 arg1 sequences 552:560 the amino acid sequences 537:560 the amino acid sequences of the asparaginyl endopeptidases of other parasitic helminths 537:623 This putative protein was determined to have 37-65% identity in the amino acid sequences of the asparaginyl endopeptidases of other parasitic helminths. 28735024 5 0 gly N-glycosylated 897:910 arg1 protein 886:892 Arabidopsis p24δ5 protein 868:892 Arabidopsis p24δ5 protein 868:892 Here, we show that Arabidopsis p24δ5 protein is N-glycosylated in its GOLD domain. 28735024 5 0 gly N-glycosylated 897:910 arg2 protein 886:892 Arabidopsis p24δ5 protein 868:892 Arabidopsis p24δ5 protein 868:892 Here, we show that Arabidopsis p24δ5 protein is N-glycosylated in its GOLD domain. 28735024 5 0 gly N-glycosylated 897:910 arg1 domain 924:929 its GOLD domain 915:929 its GOLD domain 915:929 Here, we show that Arabidopsis p24δ5 protein is N-glycosylated in its GOLD domain. 28735024 6 1 theme coupled 1023:1029 arg1 transport 1031:1039 its coupled transport 1019:1039 its coupled transport with p24β2 at the ER-Golgi interface 1019:1076 Furthermore, we demonstrate that this post-translational modification is important for its coupled transport with p24β2 at the ER-Golgi interface, for its interaction with the K/HDEL receptor ERD2, and for retrograde transport of ERD2 and K/HDEL ligands from the Golgi apparatus back to the ER. 28735024 4 2 from members 647:653 arg1 function 824:831 p24 function 820:831 p24 function 820:831 Several members of the p24 family in mammals and yeast have been shown to be glycosylated, but whether Arabidopsis p24 proteins are glycosylated and the role of the sugar moiety in p24 function remain unclear. 28735024 1 3 theme C-terminal 249:258 arg1 signal 267:272 a C-terminal K/HDEL signal 247:272 a C-terminal K/HDEL signal from the Golgi apparatus 247:297 The K/HDEL receptor ERD2 mediates the transport of soluble endoplasmic reticulum (ER)-resident proteins containing a C-terminal K/HDEL signal from the Golgi apparatus back to the ER via COPI (COat Protein I)-coated vesicles. 28735024 0 4 theme Golgi-to-ER 76:86 arg1 Transport 88:96 Retrograde Golgi-to-ER Transport 65:96 Retrograde Golgi-to-ER Transport of K/HDEL Ligands in Arabidopsis 65:129 N-Linked Glycosylation of the p24 Family Protein p24δ5 Modulates Retrograde Golgi-to-ER Transport of K/HDEL Ligands in Arabidopsis. 28735024 1 5 theme COat 324:327 arg1 vesicles 347:354 COPI (COat Protein I)-coated vesicles 318:354 COPI (COat Protein I)-coated vesicles 318:354 The K/HDEL receptor ERD2 mediates the transport of soluble endoplasmic reticulum (ER)-resident proteins containing a C-terminal K/HDEL signal from the Golgi apparatus back to the ER via COPI (COat Protein I)-coated vesicles. 28735024 6 6 theme Golgi 1195:1199 arg1 apparatus 1201:1209 the Golgi apparatus 1191:1209 the Golgi apparatus 1191:1209 Furthermore, we demonstrate that this post-translational modification is important for its coupled transport with p24β2 at the ER-Golgi interface, for its interaction with the K/HDEL receptor ERD2, and for retrograde transport of ERD2 and K/HDEL ligands from the Golgi apparatus back to the ER. 28735024 1 7 theme K/HDEL 260:265 arg1 signal 267:272 a C-terminal K/HDEL signal 247:272 a C-terminal K/HDEL signal from the Golgi apparatus 247:297 The K/HDEL receptor ERD2 mediates the transport of soluble endoplasmic reticulum (ER)-resident proteins containing a C-terminal K/HDEL signal from the Golgi apparatus back to the ER via COPI (COat Protein I)-coated vesicles. 28735024 0 8 theme K/HDEL 101:106 arg1 Ligands 108:114 K/HDEL Ligands 101:114 K/HDEL Ligands 101:114 N-Linked Glycosylation of the p24 Family Protein p24δ5 Modulates Retrograde Golgi-to-ER Transport of K/HDEL Ligands in Arabidopsis. 28735024 1 9 theme Protein I 329:337 arg1 vesicles 347:354 COPI (COat Protein I)-coated vesicles 318:354 COPI (COat Protein I)-coated vesicles 318:354 The K/HDEL receptor ERD2 mediates the transport of soluble endoplasmic reticulum (ER)-resident proteins containing a C-terminal K/HDEL signal from the Golgi apparatus back to the ER via COPI (COat Protein I)-coated vesicles. 28735024 3 10 theme acidic 605:610 arg1 pH 612:613 the acidic pH 601:613 its cytoplasmic C-terminal tail at the acidic pH of the Golgi apparatus 566:636 In Arabidopsis, p24δ5 has been shown to interact directly with ERD2 via its luminal GOLD (GOLgi Dynamics) domain and with COPI proteins via its cytoplasmic C-terminal tail at the acidic pH of the Golgi apparatus. 28735024 3 11 theme luminal 502:508 arg1 domain and 532:541 its luminal GOLD (GOLgi Dynamics) domain and 498:541 its luminal GOLD (GOLgi Dynamics) domain and with COPI proteins 498:560 In Arabidopsis, p24δ5 has been shown to interact directly with ERD2 via its luminal GOLD (GOLgi Dynamics) domain and with COPI proteins via its cytoplasmic C-terminal tail at the acidic pH of the Golgi apparatus. 28735024 5 12 theme Arabidopsis 868:878 arg1 protein 886:892 Arabidopsis p24δ5 protein 868:892 Arabidopsis p24δ5 protein 868:892 Here, we show that Arabidopsis p24δ5 protein is N-glycosylated in its GOLD domain. 28735024 4 13 from role 792:795 arg1 function 824:831 p24 function 820:831 p24 function 820:831 Several members of the p24 family in mammals and yeast have been shown to be glycosylated, but whether Arabidopsis p24 proteins are glycosylated and the role of the sugar moiety in p24 function remain unclear. 28735024 4 14 theme sugar 804:808 arg1 moiety 810:815 the sugar moiety 800:815 the sugar moiety 800:815 Several members of the p24 family in mammals and yeast have been shown to be glycosylated, but whether Arabidopsis p24 proteins are glycosylated and the role of the sugar moiety in p24 function remain unclear. 28735024 3 15 theme GOLD  510:514 arg1 domain and 532:541 its luminal GOLD (GOLgi Dynamics) domain and 498:541 its luminal GOLD (GOLgi Dynamics) domain and with COPI proteins 498:560 In Arabidopsis, p24δ5 has been shown to interact directly with ERD2 via its luminal GOLD (GOLgi Dynamics) domain and with COPI proteins via its cytoplasmic C-terminal tail at the acidic pH of the Golgi apparatus. 28735024 4 16 theme family 666:671 arg1 members 647:653 Several members 639:653 Several members of the p24 family in mammals and yeast have been shown to be glycosylated, but whether Arabidopsis p24 proteins are glycosylated 639:782 Several members of the p24 family in mammals and yeast have been shown to be glycosylated, but whether Arabidopsis p24 proteins are glycosylated and the role of the sugar moiety in p24 function remain unclear. 28735024 4 16 theme family 666:671 arg1 role 792:795 the role 788:795 the role of the sugar moiety in p24 function 788:831 Several members of the p24 family in mammals and yeast have been shown to be glycosylated, but whether Arabidopsis p24 proteins are glycosylated and the role of the sugar moiety in p24 function remain unclear. 28735024 1 17 theme -coated 339:345 arg1 vesicles 347:354 COPI (COat Protein I)-coated vesicles 318:354 COPI (COat Protein I)-coated vesicles 318:354 The K/HDEL receptor ERD2 mediates the transport of soluble endoplasmic reticulum (ER)-resident proteins containing a C-terminal K/HDEL signal from the Golgi apparatus back to the ER via COPI (COat Protein I)-coated vesicles. 28735024 1 18 from apparatus 289:297 arg1 signal 267:272 a C-terminal K/HDEL signal 247:272 a C-terminal K/HDEL signal from the Golgi apparatus 247:297 The K/HDEL receptor ERD2 mediates the transport of soluble endoplasmic reticulum (ER)-resident proteins containing a C-terminal K/HDEL signal from the Golgi apparatus back to the ER via COPI (COat Protein I)-coated vesicles. 28735024 5 19 from N-glycosylated 897:910 arg1 domain 924:929 its GOLD domain 915:929 its GOLD domain 915:929 Here, we show that Arabidopsis p24δ5 protein is N-glycosylated in its GOLD domain. 28735024 5 20 from domain 924:929 arg1 N-glycosylated 897:910 N-glycosylated 897:910 N-glycosylated 897:910 Here, we show that Arabidopsis p24δ5 protein is N-glycosylated in its GOLD domain. 28735024 4 21 theme Arabidopsis 742:752 arg1 proteins 758:765 Arabidopsis p24 proteins 742:765 Arabidopsis p24 proteins 742:765 Several members of the p24 family in mammals and yeast have been shown to be glycosylated, but whether Arabidopsis p24 proteins are glycosylated and the role of the sugar moiety in p24 function remain unclear. 28735024 0 22 theme Ligands 108:114 arg1 Transport 88:96 Retrograde Golgi-to-ER Transport 65:96 Retrograde Golgi-to-ER Transport of K/HDEL Ligands in Arabidopsis 65:129 N-Linked Glycosylation of the p24 Family Protein p24δ5 Modulates Retrograde Golgi-to-ER Transport of K/HDEL Ligands in Arabidopsis. 28735024 4 23 gly glycosylated 716:727 arg1 yeast 688:692 yeast 688:692 yeast 688:692 Several members of the p24 family in mammals and yeast have been shown to be glycosylated, but whether Arabidopsis p24 proteins are glycosylated and the role of the sugar moiety in p24 function remain unclear. 28735024 4 23 gly glycosylated 716:727 arg1 mammals 676:682 mammals 676:682 mammals 676:682 Several members of the p24 family in mammals and yeast have been shown to be glycosylated, but whether Arabidopsis p24 proteins are glycosylated and the role of the sugar moiety in p24 function remain unclear. 28735024 2 24 theme ERD2 368:371 arg1 Sorting 357:363 Sorting 357:363 Sorting of ERD2 within COPI vesicles 357:392 Sorting of ERD2 within COPI vesicles is facilitated by p24 proteins. 28735024 6 25 with transport 1031:1039 arg1 p24β2 1046:1050 p24β2 1046:1050 p24β2 1046:1050 Furthermore, we demonstrate that this post-translational modification is important for its coupled transport with p24β2 at the ER-Golgi interface, for its interaction with the K/HDEL receptor ERD2, and for retrograde transport of ERD2 and K/HDEL ligands from the Golgi apparatus back to the ER. 28735024 3 26 theme Dynamics 522:529 arg1 domain and 532:541 its luminal GOLD (GOLgi Dynamics) domain and 498:541 its luminal GOLD (GOLgi Dynamics) domain and with COPI proteins 498:560 In Arabidopsis, p24δ5 has been shown to interact directly with ERD2 via its luminal GOLD (GOLgi Dynamics) domain and with COPI proteins via its cytoplasmic C-terminal tail at the acidic pH of the Golgi apparatus. 28735024 1 27 theme soluble 183:189 arg1 ER 214:215 ER 214:215 ER 214:215 The K/HDEL receptor ERD2 mediates the transport of soluble endoplasmic reticulum (ER)-resident proteins containing a C-terminal K/HDEL signal from the Golgi apparatus back to the ER via COPI (COat Protein I)-coated vesicles. 28735024 1 27 theme soluble 183:189 arg1 reticulum 203:211 soluble endoplasmic reticulum 183:211 soluble endoplasmic reticulum (ER)-resident proteins containing a C-terminal K/HDEL signal from the Golgi apparatus 183:297 The K/HDEL receptor ERD2 mediates the transport of soluble endoplasmic reticulum (ER)-resident proteins containing a C-terminal K/HDEL signal from the Golgi apparatus back to the ER via COPI (COat Protein I)-coated vesicles. 28735024 0 28 theme N-Linked 0:7 arg1 Glycosylation 9:21 N-Linked Glycosylation 0:21 N-Linked Glycosylation of the p24 Family Protein p24δ5 0:53 N-Linked Glycosylation of the p24 Family Protein p24δ5 Modulates Retrograde Golgi-to-ER Transport of K/HDEL Ligands in Arabidopsis. 28735024 6 29 theme ligands 1178:1184 arg1 transport 1149:1157 retrograde transport 1138:1157 retrograde transport of ERD2 and K/HDEL ligands from the Golgi apparatus back to the ER 1138:1224 Furthermore, we demonstrate that this post-translational modification is important for its coupled transport with p24β2 at the ER-Golgi interface, for its interaction with the K/HDEL receptor ERD2, and for retrograde transport of ERD2 and K/HDEL ligands from the Golgi apparatus back to the ER. 28735024 6 30 theme ERD2 1162:1165 arg1 ligands 1178:1184 ERD2 and K/HDEL ligands 1162:1184 ERD2 and K/HDEL ligands 1162:1184 Furthermore, we demonstrate that this post-translational modification is important for its coupled transport with p24β2 at the ER-Golgi interface, for its interaction with the K/HDEL receptor ERD2, and for retrograde transport of ERD2 and K/HDEL ligands from the Golgi apparatus back to the ER. 28735024 6 31 theme post-translational 970:987 arg1 modification 989:1000 this post-translational modification 965:1000 this post-translational modification 965:1000 Furthermore, we demonstrate that this post-translational modification is important for its coupled transport with p24β2 at the ER-Golgi interface, for its interaction with the K/HDEL receptor ERD2, and for retrograde transport of ERD2 and K/HDEL ligands from the Golgi apparatus back to the ER. 28735024 4 32 dep family 666:671 arg1 shown 704:708 shown 704:708 have been shown to be glycosylated 694:727 Several members of the p24 family in mammals and yeast have been shown to be glycosylated, but whether Arabidopsis p24 proteins are glycosylated and the role of the sugar moiety in p24 function remain unclear. 28735024 4 32 dep family 666:671 arg1 glycosylated 771:782 glycosylated 771:782 are glycosylated 767:782 Several members of the p24 family in mammals and yeast have been shown to be glycosylated, but whether Arabidopsis p24 proteins are glycosylated and the role of the sugar moiety in p24 function remain unclear. 28735024 1 33 theme endoplasmic 191:201 arg1 ER 214:215 ER 214:215 ER 214:215 The K/HDEL receptor ERD2 mediates the transport of soluble endoplasmic reticulum (ER)-resident proteins containing a C-terminal K/HDEL signal from the Golgi apparatus back to the ER via COPI (COat Protein I)-coated vesicles. 28735024 1 33 theme endoplasmic 191:201 arg1 reticulum 203:211 soluble endoplasmic reticulum 183:211 soluble endoplasmic reticulum (ER)-resident proteins containing a C-terminal K/HDEL signal from the Golgi apparatus 183:297 The K/HDEL receptor ERD2 mediates the transport of soluble endoplasmic reticulum (ER)-resident proteins containing a C-terminal K/HDEL signal from the Golgi apparatus back to the ER via COPI (COat Protein I)-coated vesicles. 28735024 2 34 theme p24 412:414 arg1 proteins 416:423 p24 proteins 412:423 p24 proteins 412:423 Sorting of ERD2 within COPI vesicles is facilitated by p24 proteins. 28735024 1 35 theme Golgi 283:287 arg1 apparatus 289:297 the Golgi apparatus 279:297 the Golgi apparatus 279:297 The K/HDEL receptor ERD2 mediates the transport of soluble endoplasmic reticulum (ER)-resident proteins containing a C-terminal K/HDEL signal from the Golgi apparatus back to the ER via COPI (COat Protein I)-coated vesicles. 28735024 4 36 theme p24 754:756 arg1 proteins 758:765 Arabidopsis p24 proteins 742:765 Arabidopsis p24 proteins 742:765 Several members of the p24 family in mammals and yeast have been shown to be glycosylated, but whether Arabidopsis p24 proteins are glycosylated and the role of the sugar moiety in p24 function remain unclear. 28735024 1 37 theme reticulum 203:211 arg1 proteins 227:234 soluble endoplasmic reticulum (ER)-resident proteins 183:234 soluble endoplasmic reticulum (ER)-resident proteins containing a C-terminal K/HDEL signal from the Golgi apparatus 183:297 The K/HDEL receptor ERD2 mediates the transport of soluble endoplasmic reticulum (ER)-resident proteins containing a C-terminal K/HDEL signal from the Golgi apparatus back to the ER via COPI (COat Protein I)-coated vesicles. 28735024 6 38 theme K/HDEL 1108:1113 arg1 ERD2 1124:1127 the K/HDEL receptor ERD2 1104:1127 the K/HDEL receptor ERD2 1104:1127 Furthermore, we demonstrate that this post-translational modification is important for its coupled transport with p24β2 at the ER-Golgi interface, for its interaction with the K/HDEL receptor ERD2, and for retrograde transport of ERD2 and K/HDEL ligands from the Golgi apparatus back to the ER. 28735024 6 39 from interface 1068:1076 arg1 transport 1031:1039 its coupled transport 1019:1039 its coupled transport with p24β2 at the ER-Golgi interface 1019:1076 Furthermore, we demonstrate that this post-translational modification is important for its coupled transport with p24β2 at the ER-Golgi interface, for its interaction with the K/HDEL receptor ERD2, and for retrograde transport of ERD2 and K/HDEL ligands from the Golgi apparatus back to the ER. 28735024 0 40 from Transport 88:96 arg1 Arabidopsis 119:129 Arabidopsis 119:129 Arabidopsis 119:129 N-Linked Glycosylation of the p24 Family Protein p24δ5 Modulates Retrograde Golgi-to-ER Transport of K/HDEL Ligands in Arabidopsis. 28735024 3 41 theme GOLgi 516:520 arg1 domain and 532:541 its luminal GOLD (GOLgi Dynamics) domain and 498:541 its luminal GOLD (GOLgi Dynamics) domain and with COPI proteins 498:560 In Arabidopsis, p24δ5 has been shown to interact directly with ERD2 via its luminal GOLD (GOLgi Dynamics) domain and with COPI proteins via its cytoplasmic C-terminal tail at the acidic pH of the Golgi apparatus. 28735024 4 42 theme Several 639:645 arg1 members 647:653 Several members 639:653 Several members of the p24 family in mammals and yeast have been shown to be glycosylated, but whether Arabidopsis p24 proteins are glycosylated 639:782 Several members of the p24 family in mammals and yeast have been shown to be glycosylated, but whether Arabidopsis p24 proteins are glycosylated and the role of the sugar moiety in p24 function remain unclear. 28735024 0 43 theme Family 34:39 arg1 p24δ5 49:53 the p24 Family Protein p24δ5 26:53 the p24 Family Protein p24δ5 26:53 N-Linked Glycosylation of the p24 Family Protein p24δ5 Modulates Retrograde Golgi-to-ER Transport of K/HDEL Ligands in Arabidopsis. 28735024 5 44 theme p24δ5 880:884 arg1 protein 886:892 Arabidopsis p24δ5 protein 868:892 Arabidopsis p24δ5 protein 868:892 Here, we show that Arabidopsis p24δ5 protein is N-glycosylated in its GOLD domain. 28735024 3 45 theme COPI 548:551 arg1 proteins 553:560 COPI proteins 548:560 COPI proteins 548:560 In Arabidopsis, p24δ5 has been shown to interact directly with ERD2 via its luminal GOLD (GOLgi Dynamics) domain and with COPI proteins via its cytoplasmic C-terminal tail at the acidic pH of the Golgi apparatus. 28735024 0 46 theme p24 30:32 arg1 p24δ5 49:53 the p24 Family Protein p24δ5 26:53 the p24 Family Protein p24δ5 26:53 N-Linked Glycosylation of the p24 Family Protein p24δ5 Modulates Retrograde Golgi-to-ER Transport of K/HDEL Ligands in Arabidopsis. 28735024 1 47 contain containing 236:245 arg2 signal 267:272 a C-terminal K/HDEL signal 247:272 a C-terminal K/HDEL signal from the Golgi apparatus 247:297 The K/HDEL receptor ERD2 mediates the transport of soluble endoplasmic reticulum (ER)-resident proteins containing a C-terminal K/HDEL signal from the Golgi apparatus back to the ER via COPI (COat Protein I)-coated vesicles. 28735024 1 47 contain containing 236:245 arg1 proteins 227:234 soluble endoplasmic reticulum (ER)-resident proteins 183:234 soluble endoplasmic reticulum (ER)-resident proteins containing a C-terminal K/HDEL signal from the Golgi apparatus 183:297 The K/HDEL receptor ERD2 mediates the transport of soluble endoplasmic reticulum (ER)-resident proteins containing a C-terminal K/HDEL signal from the Golgi apparatus back to the ER via COPI (COat Protein I)-coated vesicles. 28735024 2 48 theme COPI 380:383 arg1 vesicles 385:392 COPI vesicles 380:392 COPI vesicles 380:392 Sorting of ERD2 within COPI vesicles is facilitated by p24 proteins. 28735024 0 49 theme p24δ5 49:53 arg1 Glycosylation 9:21 N-Linked Glycosylation 0:21 N-Linked Glycosylation of the p24 Family Protein p24δ5 0:53 N-Linked Glycosylation of the p24 Family Protein p24δ5 Modulates Retrograde Golgi-to-ER Transport of K/HDEL Ligands in Arabidopsis. 28735024 3 50 with domain and 532:541 arg1 proteins 553:560 COPI proteins 548:560 COPI proteins 548:560 In Arabidopsis, p24δ5 has been shown to interact directly with ERD2 via its luminal GOLD (GOLgi Dynamics) domain and with COPI proteins via its cytoplasmic C-terminal tail at the acidic pH of the Golgi apparatus. 28735024 4 51 theme p24 820:822 arg1 function 824:831 p24 function 820:831 p24 function 820:831 Several members of the p24 family in mammals and yeast have been shown to be glycosylated, but whether Arabidopsis p24 proteins are glycosylated and the role of the sugar moiety in p24 function remain unclear. 28735024 6 52 with interaction 1087:1097 arg1 ERD2 1124:1127 the K/HDEL receptor ERD2 1104:1127 the K/HDEL receptor ERD2 1104:1127 Furthermore, we demonstrate that this post-translational modification is important for its coupled transport with p24β2 at the ER-Golgi interface, for its interaction with the K/HDEL receptor ERD2, and for retrograde transport of ERD2 and K/HDEL ligands from the Golgi apparatus back to the ER. 28735024 6 53 theme retrograde 1138:1147 arg1 transport 1149:1157 retrograde transport 1138:1157 retrograde transport of ERD2 and K/HDEL ligands from the Golgi apparatus back to the ER 1138:1224 Furthermore, we demonstrate that this post-translational modification is important for its coupled transport with p24β2 at the ER-Golgi interface, for its interaction with the K/HDEL receptor ERD2, and for retrograde transport of ERD2 and K/HDEL ligands from the Golgi apparatus back to the ER. 28735024 4 54 theme p24 662:664 arg1 family 666:671 the p24 family 658:671 the p24 family in mammals and yeast have been shown to be glycosylated, but whether Arabidopsis p24 proteins are glycosylated 658:782 Several members of the p24 family in mammals and yeast have been shown to be glycosylated, but whether Arabidopsis p24 proteins are glycosylated and the role of the sugar moiety in p24 function remain unclear. 28735024 0 55 theme Protein 41:47 arg1 p24δ5 49:53 the p24 Family Protein p24δ5 26:53 the p24 Family Protein p24δ5 26:53 N-Linked Glycosylation of the p24 Family Protein p24δ5 Modulates Retrograde Golgi-to-ER Transport of K/HDEL Ligands in Arabidopsis. 28735024 3 56 theme Golgi 622:626 arg1 apparatus 628:636 the Golgi apparatus 618:636 the Golgi apparatus 618:636 In Arabidopsis, p24δ5 has been shown to interact directly with ERD2 via its luminal GOLD (GOLgi Dynamics) domain and with COPI proteins via its cytoplasmic C-terminal tail at the acidic pH of the Golgi apparatus. 28735024 6 57 theme K/HDEL 1171:1176 arg1 ligands 1178:1184 ERD2 and K/HDEL ligands 1162:1184 ERD2 and K/HDEL ligands 1162:1184 Furthermore, we demonstrate that this post-translational modification is important for its coupled transport with p24β2 at the ER-Golgi interface, for its interaction with the K/HDEL receptor ERD2, and for retrograde transport of ERD2 and K/HDEL ligands from the Golgi apparatus back to the ER. 28735024 4 58 theme moiety 810:815 arg1 members 647:653 Several members 639:653 Several members of the p24 family in mammals and yeast have been shown to be glycosylated, but whether Arabidopsis p24 proteins are glycosylated 639:782 Several members of the p24 family in mammals and yeast have been shown to be glycosylated, but whether Arabidopsis p24 proteins are glycosylated and the role of the sugar moiety in p24 function remain unclear. 28735024 4 58 theme moiety 810:815 arg1 role 792:795 the role 788:795 the role of the sugar moiety in p24 function 788:831 Several members of the p24 family in mammals and yeast have been shown to be glycosylated, but whether Arabidopsis p24 proteins are glycosylated and the role of the sugar moiety in p24 function remain unclear. 28735024 3 59 theme apparatus 628:636 arg1 tail at 593:599 its cytoplasmic C-terminal tail at 566:599 its cytoplasmic C-terminal tail at the acidic pH of the Golgi apparatus 566:636 In Arabidopsis, p24δ5 has been shown to interact directly with ERD2 via its luminal GOLD (GOLgi Dynamics) domain and with COPI proteins via its cytoplasmic C-terminal tail at the acidic pH of the Golgi apparatus. 28735024 3 60 theme cytoplasmic 570:580 arg1 tail at 593:599 its cytoplasmic C-terminal tail at 566:599 its cytoplasmic C-terminal tail at the acidic pH of the Golgi apparatus 566:636 In Arabidopsis, p24δ5 has been shown to interact directly with ERD2 via its luminal GOLD (GOLgi Dynamics) domain and with COPI proteins via its cytoplasmic C-terminal tail at the acidic pH of the Golgi apparatus. 28735024 0 61 gly Glycosylation 9:21 arg1 p24δ5 49:53 the p24 Family Protein p24δ5 26:53 the p24 Family Protein p24δ5 26:53 N-Linked Glycosylation of the p24 Family Protein p24δ5 Modulates Retrograde Golgi-to-ER Transport of K/HDEL Ligands in Arabidopsis. 28735024 1 62 theme -resident 217:225 arg1 proteins 227:234 soluble endoplasmic reticulum (ER)-resident proteins 183:234 soluble endoplasmic reticulum (ER)-resident proteins containing a C-terminal K/HDEL signal from the Golgi apparatus 183:297 The K/HDEL receptor ERD2 mediates the transport of soluble endoplasmic reticulum (ER)-resident proteins containing a C-terminal K/HDEL signal from the Golgi apparatus back to the ER via COPI (COat Protein I)-coated vesicles. 28735024 3 63 theme C-terminal 582:591 arg1 tail at 593:599 its cytoplasmic C-terminal tail at 566:599 its cytoplasmic C-terminal tail at the acidic pH of the Golgi apparatus 566:636 In Arabidopsis, p24δ5 has been shown to interact directly with ERD2 via its luminal GOLD (GOLgi Dynamics) domain and with COPI proteins via its cytoplasmic C-terminal tail at the acidic pH of the Golgi apparatus. 28735024 1 64 theme K/HDEL 136:141 arg1 ERD2 152:155 The K/HDEL receptor ERD2 132:155 The K/HDEL receptor ERD2 132:155 The K/HDEL receptor ERD2 mediates the transport of soluble endoplasmic reticulum (ER)-resident proteins containing a C-terminal K/HDEL signal from the Golgi apparatus back to the ER via COPI (COat Protein I)-coated vesicles. 28735024 6 65 theme ER-Golgi 1059:1066 arg1 interface 1068:1076 the ER-Golgi interface 1055:1076 the ER-Golgi interface 1055:1076 Furthermore, we demonstrate that this post-translational modification is important for its coupled transport with p24β2 at the ER-Golgi interface, for its interaction with the K/HDEL receptor ERD2, and for retrograde transport of ERD2 and K/HDEL ligands from the Golgi apparatus back to the ER. 28735024 1 66 theme proteins 227:234 arg1 transport 170:178 the transport 166:178 the transport of soluble endoplasmic reticulum (ER)-resident proteins containing a C-terminal K/HDEL signal from the Golgi apparatus back to the ER 166:312 The K/HDEL receptor ERD2 mediates the transport of soluble endoplasmic reticulum (ER)-resident proteins containing a C-terminal K/HDEL signal from the Golgi apparatus back to the ER via COPI (COat Protein I)-coated vesicles. 28735024 0 67 theme Retrograde 65:74 arg1 Transport 88:96 Retrograde Golgi-to-ER Transport 65:96 Retrograde Golgi-to-ER Transport of K/HDEL Ligands in Arabidopsis 65:129 N-Linked Glycosylation of the p24 Family Protein p24δ5 Modulates Retrograde Golgi-to-ER Transport of K/HDEL Ligands in Arabidopsis. 28735024 5 68 theme GOLD 919:922 arg1 domain 924:929 its GOLD domain 915:929 its GOLD domain 915:929 Here, we show that Arabidopsis p24δ5 protein is N-glycosylated in its GOLD domain. 28735024 4 69 gly glycosylated 771:782 arg1 family 666:671 the p24 family 658:671 the p24 family in mammals and yeast have been shown to be glycosylated, but whether Arabidopsis p24 proteins are glycosylated 658:782 Several members of the p24 family in mammals and yeast have been shown to be glycosylated, but whether Arabidopsis p24 proteins are glycosylated and the role of the sugar moiety in p24 function remain unclear. 28735024 4 69 gly glycosylated 771:782 arg1 proteins 758:765 Arabidopsis p24 proteins 742:765 Arabidopsis p24 proteins 742:765 Several members of the p24 family in mammals and yeast have been shown to be glycosylated, but whether Arabidopsis p24 proteins are glycosylated and the role of the sugar moiety in p24 function remain unclear. 28735024 1 70 theme receptor 143:150 arg1 ERD2 152:155 The K/HDEL receptor ERD2 132:155 The K/HDEL receptor ERD2 132:155 The K/HDEL receptor ERD2 mediates the transport of soluble endoplasmic reticulum (ER)-resident proteins containing a C-terminal K/HDEL signal from the Golgi apparatus back to the ER via COPI (COat Protein I)-coated vesicles. 28735024 6 71 from apparatus 1201:1209 arg1 transport 1149:1157 retrograde transport 1138:1157 retrograde transport of ERD2 and K/HDEL ligands from the Golgi apparatus back to the ER 1138:1224 Furthermore, we demonstrate that this post-translational modification is important for its coupled transport with p24β2 at the ER-Golgi interface, for its interaction with the K/HDEL receptor ERD2, and for retrograde transport of ERD2 and K/HDEL ligands from the Golgi apparatus back to the ER. 28735024 1 72 theme COPI 318:321 arg1 vesicles 347:354 COPI (COat Protein I)-coated vesicles 318:354 COPI (COat Protein I)-coated vesicles 318:354 The K/HDEL receptor ERD2 mediates the transport of soluble endoplasmic reticulum (ER)-resident proteins containing a C-terminal K/HDEL signal from the Golgi apparatus back to the ER via COPI (COat Protein I)-coated vesicles. 28735024 6 73 theme receptor 1115:1122 arg1 ERD2 1124:1127 the K/HDEL receptor ERD2 1104:1127 the K/HDEL receptor ERD2 1104:1127 Furthermore, we demonstrate that this post-translational modification is important for its coupled transport with p24β2 at the ER-Golgi interface, for its interaction with the K/HDEL receptor ERD2, and for retrograde transport of ERD2 and K/HDEL ligands from the Golgi apparatus back to the ER. 28735024 3 74 dep tail at 593:599 arg1 pH 612:613 the acidic pH 601:613 its cytoplasmic C-terminal tail at the acidic pH of the Golgi apparatus 566:636 In Arabidopsis, p24δ5 has been shown to interact directly with ERD2 via its luminal GOLD (GOLgi Dynamics) domain and with COPI proteins via its cytoplasmic C-terminal tail at the acidic pH of the Golgi apparatus. 28188526 0 0 theme Intact 89:94 arg1 Glycoforms 104:113 Intact Protein Glycoforms 89:113 Intact Protein Glycoforms 89:113 Multi-Lectin Affinity Chromatography for Separation, Identification, and Quantitation of Intact Protein Glycoforms in Complex Biological Mixtures. 28188526 2 1 theme complex 525:531 arg1 mixtures 533:540 complex mixtures 525:540 complex mixtures extracted from various biological samples (such as blood and tissue) 525:609 Aberrant N-linked glycosylation has been associated with several human diseases and has prompted the development and constant improvement of analytical tools to separate, characterize, and quantify glycoproteins in complex mixtures extracted from various biological samples (such as blood and tissue). 28188526 6 2 theme Reversed-phase 1121:1134 arg1 chromatography 1136:1149 Reversed-phase chromatography 1121:1149 Reversed-phase chromatography prior to digestion 1121:1168 Reversed-phase chromatography prior to digestion is used for further fractionation, allowing for an increased number of protein identifications of moderate- to low-abundant proteins detectable in plasma. 28188526 6 3 theme protein 1241:1247 arg1 identifications 1249:1263 protein identifications 1241:1263 protein identifications of moderate- to low-abundant proteins detectable in plasma 1241:1322 Reversed-phase chromatography prior to digestion is used for further fractionation, allowing for an increased number of protein identifications of moderate- to low-abundant proteins detectable in plasma. 28188526 3 4 theme specific 738:745 arg1 types 747:751 specific types 738:751 specific types of glycosylation 738:768 Lectins, or carbohydrate-binding proteins, have been used as valuable tools for enriching for glycoproteins and selecting for specific types of glycosylation. 28188526 8 5 theme bottom-up 1469:1477 arg1 approach 1522:1529 A bottom-up, tandem mass spectrometry-based proteomics approach 1467:1529 approach 1522:1529 A bottom-up, tandem mass spectrometry-based proteomics approach is used for protein identification and quantitation, and allows for screening glycoform-specific changes across hundreds of plasma proteins. 28188526 1 6 theme key 277:279 arg1 roles 281:285 key roles 277:285 key roles 277:285 Protein glycosylation is considered to be one of the most abundant post-translational modifications and is recognized for playing key roles in cellular functions. 28188526 0 7 theme Glycoforms 104:113 arg1 Identification 53:66 Identification 53:66 Identification 53:66 Multi-Lectin Affinity Chromatography for Separation, Identification, and Quantitation of Intact Protein Glycoforms in Complex Biological Mixtures. 28188526 0 7 theme Glycoforms 104:113 arg1 Quantitation 73:84 Quantitation 73:84 Quantitation 73:84 Multi-Lectin Affinity Chromatography for Separation, Identification, and Quantitation of Intact Protein Glycoforms in Complex Biological Mixtures. 28188526 0 7 theme Glycoforms 104:113 arg1 Separation 41:50 Separation 41:50 Separation 41:50 Multi-Lectin Affinity Chromatography for Separation, Identification, and Quantitation of Intact Protein Glycoforms in Complex Biological Mixtures. 28188526 6 8 theme detectable 1303:1312 arg1 proteins 1294:1301 low-abundant proteins 1281:1301 low-abundant proteins detectable in plasma 1281:1322 Reversed-phase chromatography prior to digestion is used for further fractionation, allowing for an increased number of protein identifications of moderate- to low-abundant proteins detectable in plasma. 28188526 6 9 theme identifications 1249:1263 arg1 number 1231:1236 an increased number 1218:1236 an increased number of protein identifications of moderate- to low-abundant proteins detectable in plasma 1218:1322 Reversed-phase chromatography prior to digestion is used for further fractionation, allowing for an increased number of protein identifications of moderate- to low-abundant proteins detectable in plasma. 28188526 2 10 theme Aberrant 310:317 arg1 glycosylation 328:340 Aberrant N-linked glycosylation 310:340 Aberrant N-linked glycosylation 310:340 Aberrant N-linked glycosylation has been associated with several human diseases and has prompted the development and constant improvement of analytical tools to separate, characterize, and quantify glycoproteins in complex mixtures extracted from various biological samples (such as blood and tissue). 28188526 6 11 theme increased 1221:1229 arg1 number 1231:1236 an increased number 1218:1236 an increased number of protein identifications of moderate- to low-abundant proteins detectable in plasma 1218:1322 Reversed-phase chromatography prior to digestion is used for further fractionation, allowing for an increased number of protein identifications of moderate- to low-abundant proteins detectable in plasma. 28188526 0 12 theme Protein 96:102 arg1 Glycoforms 104:113 Intact Protein Glycoforms 89:113 Intact Protein Glycoforms 89:113 Multi-Lectin Affinity Chromatography for Separation, Identification, and Quantitation of Intact Protein Glycoforms in Complex Biological Mixtures. 28188526 3 13 theme glycosylation 756:768 arg1 types 747:751 specific types 738:751 specific types of glycosylation 738:768 Lectins, or carbohydrate-binding proteins, have been used as valuable tools for enriching for glycoproteins and selecting for specific types of glycosylation. 28188526 5 14 theme specific 1039:1046 arg1 lectins 1048:1054 specific lectins 1039:1054 specific lectins 1039:1054 Immunodepletion is used to remove highly abundant proteins from human plasma, followed by glycoform separation using multi-lectin affinity chromatography, in which specific lectins are chosen to capture and elute specific types of glycosylation. 28188526 4 15 theme multidimensional 793:808 arg1 fractionation 825:837 multidimensional intact protein fractionation 793:837 multidimensional intact protein fractionation 793:837 Herein a method using multidimensional intact protein fractionation and LC-MS/MS analysis is described. 28188526 5 16 theme multi-lectin 992:1003 arg1 chromatography 1014:1027 multi-lectin affinity chromatography 992:1027 multi-lectin affinity chromatography 992:1027 Immunodepletion is used to remove highly abundant proteins from human plasma, followed by glycoform separation using multi-lectin affinity chromatography, in which specific lectins are chosen to capture and elute specific types of glycosylation. 28188526 2 17 theme various 557:563 arg1 samples 576:582 various biological samples 557:582 various biological samples (such as blood and tissue) 557:609 Aberrant N-linked glycosylation has been associated with several human diseases and has prompted the development and constant improvement of analytical tools to separate, characterize, and quantify glycoproteins in complex mixtures extracted from various biological samples (such as blood and tissue). 28188526 0 18 from Identification 53:66 arg1 Mixtures 137:144 Complex Biological Mixtures 118:144 Complex Biological Mixtures 118:144 Multi-Lectin Affinity Chromatography for Separation, Identification, and Quantitation of Intact Protein Glycoforms in Complex Biological Mixtures. 28188526 2 19 dep separate 471:478 arg1 characterize 481:492 characterize 481:492 characterize 481:492 Aberrant N-linked glycosylation has been associated with several human diseases and has prompted the development and constant improvement of analytical tools to separate, characterize, and quantify glycoproteins in complex mixtures extracted from various biological samples (such as blood and tissue). 28188526 2 19 dep separate 471:478 arg1 quantify 499:506 quantify 499:506 quantify glycoproteins in complex mixtures extracted from various biological samples (such as blood and tissue) 499:609 Aberrant N-linked glycosylation has been associated with several human diseases and has prompted the development and constant improvement of analytical tools to separate, characterize, and quantify glycoproteins in complex mixtures extracted from various biological samples (such as blood and tissue). 28188526 2 20 theme analytical 451:460 arg1 tools 462:466 analytical tools 451:466 analytical tools to separate, characterize, and quantify glycoproteins in complex mixtures extracted from various biological samples (such as blood and tissue) 451:609 Aberrant N-linked glycosylation has been associated with several human diseases and has prompted the development and constant improvement of analytical tools to separate, characterize, and quantify glycoproteins in complex mixtures extracted from various biological samples (such as blood and tissue). 28188526 2 21 theme constant 427:434 arg1 improvement 436:446 constant improvement 427:446 constant improvement 427:446 Aberrant N-linked glycosylation has been associated with several human diseases and has prompted the development and constant improvement of analytical tools to separate, characterize, and quantify glycoproteins in complex mixtures extracted from various biological samples (such as blood and tissue). 28188526 8 22 theme proteins 1662:1669 arg1 hundreds 1643:1650 hundreds 1643:1650 hundreds of plasma proteins 1643:1669 A bottom-up, tandem mass spectrometry-based proteomics approach is used for protein identification and quantitation, and allows for screening glycoform-specific changes across hundreds of plasma proteins. 28188526 4 23 theme protein 817:823 arg1 fractionation 825:837 multidimensional intact protein fractionation 793:837 multidimensional intact protein fractionation 793:837 Herein a method using multidimensional intact protein fractionation and LC-MS/MS analysis is described. 28188526 0 24 theme Complex 118:124 arg1 Mixtures 137:144 Complex Biological Mixtures 118:144 Complex Biological Mixtures 118:144 Multi-Lectin Affinity Chromatography for Separation, Identification, and Quantitation of Intact Protein Glycoforms in Complex Biological Mixtures. 28188526 0 25 theme Affinity 13:20 arg1 Chromatography 22:35 Multi-Lectin Affinity Chromatography 0:35 Multi-Lectin Affinity Chromatography for Separation, Identification, and Quantitation of Intact Protein Glycoforms in Complex Biological Mixtures. 0:145 Multi-Lectin Affinity Chromatography for Separation, Identification, and Quantitation of Intact Protein Glycoforms in Complex Biological Mixtures. 28188526 0 26 from Separation 41:50 arg1 Mixtures 137:144 Complex Biological Mixtures 118:144 Complex Biological Mixtures 118:144 Multi-Lectin Affinity Chromatography for Separation, Identification, and Quantitation of Intact Protein Glycoforms in Complex Biological Mixtures. 28188526 8 27 theme tandem 1480:1485 arg1 approach 1522:1529 A bottom-up, tandem mass spectrometry-based proteomics approach 1467:1529 approach 1522:1529 A bottom-up, tandem mass spectrometry-based proteomics approach is used for protein identification and quantitation, and allows for screening glycoform-specific changes across hundreds of plasma proteins. 28188526 5 28 theme affinity 1005:1012 arg1 chromatography 1014:1027 multi-lectin affinity chromatography 992:1027 multi-lectin affinity chromatography 992:1027 Immunodepletion is used to remove highly abundant proteins from human plasma, followed by glycoform separation using multi-lectin affinity chromatography, in which specific lectins are chosen to capture and elute specific types of glycosylation. 28188526 0 29 theme Multi-Lectin 0:11 arg1 Chromatography 22:35 Multi-Lectin Affinity Chromatography 0:35 Multi-Lectin Affinity Chromatography for Separation, Identification, and Quantitation of Intact Protein Glycoforms in Complex Biological Mixtures. 0:145 Multi-Lectin Affinity Chromatography for Separation, Identification, and Quantitation of Intact Protein Glycoforms in Complex Biological Mixtures. 28188526 1 30 theme cellular 290:297 arg1 functions 299:307 cellular functions 290:307 cellular functions 290:307 Protein glycosylation is considered to be one of the most abundant post-translational modifications and is recognized for playing key roles in cellular functions. 28188526 5 31 theme human 939:943 arg1 plasma 945:950 human plasma 939:950 human plasma 939:950 Immunodepletion is used to remove highly abundant proteins from human plasma, followed by glycoform separation using multi-lectin affinity chromatography, in which specific lectins are chosen to capture and elute specific types of glycosylation. 28188526 3 32 used used 665:668 arg2 Lectins 612:618 Lectins 612:618 Lectins 612:618 Lectins, or carbohydrate-binding proteins, have been used as valuable tools for enriching for glycoproteins and selecting for specific types of glycosylation. 28188526 3 32 used used 665:668 arg2 tools 682:686 valuable tools 673:686 valuable tools for enriching for glycoproteins and selecting for specific types of glycosylation 673:768 Lectins, or carbohydrate-binding proteins, have been used as valuable tools for enriching for glycoproteins and selecting for specific types of glycosylation. 28188526 3 32 used used 665:668 arg2 proteins 645:652 carbohydrate-binding proteins 624:652 carbohydrate-binding proteins 624:652 Lectins, or carbohydrate-binding proteins, have been used as valuable tools for enriching for glycoproteins and selecting for specific types of glycosylation. 28188526 2 33 theme tools 462:466 arg1 development 411:421 development 411:421 development 411:421 Aberrant N-linked glycosylation has been associated with several human diseases and has prompted the development and constant improvement of analytical tools to separate, characterize, and quantify glycoproteins in complex mixtures extracted from various biological samples (such as blood and tissue). 28188526 2 33 theme tools 462:466 arg1 improvement 436:446 constant improvement 427:446 constant improvement 427:446 Aberrant N-linked glycosylation has been associated with several human diseases and has prompted the development and constant improvement of analytical tools to separate, characterize, and quantify glycoproteins in complex mixtures extracted from various biological samples (such as blood and tissue). 28188526 0 34 theme Biological 126:135 arg1 Mixtures 137:144 Complex Biological Mixtures 118:144 Complex Biological Mixtures 118:144 Multi-Lectin Affinity Chromatography for Separation, Identification, and Quantitation of Intact Protein Glycoforms in Complex Biological Mixtures. 28188526 3 35 theme valuable 673:680 arg1 Lectins 612:618 Lectins 612:618 Lectins 612:618 Lectins, or carbohydrate-binding proteins, have been used as valuable tools for enriching for glycoproteins and selecting for specific types of glycosylation. 28188526 3 35 theme valuable 673:680 arg1 tools 682:686 valuable tools 673:686 valuable tools for enriching for glycoproteins and selecting for specific types of glycosylation 673:768 Lectins, or carbohydrate-binding proteins, have been used as valuable tools for enriching for glycoproteins and selecting for specific types of glycosylation. 28188526 3 35 theme valuable 673:680 arg1 proteins 645:652 carbohydrate-binding proteins 624:652 carbohydrate-binding proteins 624:652 Lectins, or carbohydrate-binding proteins, have been used as valuable tools for enriching for glycoproteins and selecting for specific types of glycosylation. 28188526 2 36 theme N-linked 319:326 arg1 glycosylation 328:340 Aberrant N-linked glycosylation 310:340 Aberrant N-linked glycosylation 310:340 Aberrant N-linked glycosylation has been associated with several human diseases and has prompted the development and constant improvement of analytical tools to separate, characterize, and quantify glycoproteins in complex mixtures extracted from various biological samples (such as blood and tissue). 28188526 1 37 theme abundant 205:212 arg1 modifications 233:245 the most abundant post-translational modifications 196:245 the most abundant post-translational modifications 196:245 Protein glycosylation is considered to be one of the most abundant post-translational modifications and is recognized for playing key roles in cellular functions. 28188526 7 38 theme relative 1395:1402 arg1 quantitation 1404:1415 relative quantitation 1395:1415 relative quantitation between two samples (such as a case and control) 1395:1464 This method also incorporates isotopic labeling during alkylation for relative quantitation between two samples (such as a case and control). 28188526 2 39 dep samples 576:582 arg1 such 585:588 such 585:588 such 585:588 Aberrant N-linked glycosylation has been associated with several human diseases and has prompted the development and constant improvement of analytical tools to separate, characterize, and quantify glycoproteins in complex mixtures extracted from various biological samples (such as blood and tissue). 28188526 8 40 theme protein 1543:1549 arg1 identification 1551:1564 protein identification 1543:1564 protein identification 1543:1564 A bottom-up, tandem mass spectrometry-based proteomics approach is used for protein identification and quantitation, and allows for screening glycoform-specific changes across hundreds of plasma proteins. 28188526 8 41 theme mass 1487:1490 arg1 approach 1522:1529 A bottom-up, tandem mass spectrometry-based proteomics approach 1467:1529 approach 1522:1529 A bottom-up, tandem mass spectrometry-based proteomics approach is used for protein identification and quantitation, and allows for screening glycoform-specific changes across hundreds of plasma proteins. 28188526 6 42 theme prior 1151:1155 arg1 chromatography 1136:1149 Reversed-phase chromatography 1121:1149 Reversed-phase chromatography prior to digestion 1121:1168 Reversed-phase chromatography prior to digestion is used for further fractionation, allowing for an increased number of protein identifications of moderate- to low-abundant proteins detectable in plasma. 28188526 1 43 theme post-translational 214:231 arg1 modifications 233:245 the most abundant post-translational modifications 196:245 the most abundant post-translational modifications 196:245 Protein glycosylation is considered to be one of the most abundant post-translational modifications and is recognized for playing key roles in cellular functions. 28188526 5 44 theme abundant 916:923 arg1 proteins 925:932 highly abundant proteins 909:932 highly abundant proteins 909:932 Immunodepletion is used to remove highly abundant proteins from human plasma, followed by glycoform separation using multi-lectin affinity chromatography, in which specific lectins are chosen to capture and elute specific types of glycosylation. 28188526 0 45 from Quantitation 73:84 arg1 Mixtures 137:144 Complex Biological Mixtures 118:144 Complex Biological Mixtures 118:144 Multi-Lectin Affinity Chromatography for Separation, Identification, and Quantitation of Intact Protein Glycoforms in Complex Biological Mixtures. 28188526 2 46 gly glycoproteins 508:520 arg1 glycoproteins 508:520 glycoproteins 508:520 glycoproteins 508:520 Aberrant N-linked glycosylation has been associated with several human diseases and has prompted the development and constant improvement of analytical tools to separate, characterize, and quantify glycoproteins in complex mixtures extracted from various biological samples (such as blood and tissue). 28188526 6 47 used used 1173:1176 arg2 chromatography 1136:1149 Reversed-phase chromatography 1121:1149 Reversed-phase chromatography prior to digestion 1121:1168 Reversed-phase chromatography prior to digestion is used for further fractionation, allowing for an increased number of protein identifications of moderate- to low-abundant proteins detectable in plasma. 28188526 1 48 theme modifications 233:245 arg1 one 189:191 one 189:191 one 189:191 Protein glycosylation is considered to be one of the most abundant post-translational modifications and is recognized for playing key roles in cellular functions. 28188526 1 48 theme modifications 233:245 arg1 modifications 233:245 the most abundant post-translational modifications 196:245 the most abundant post-translational modifications 196:245 Protein glycosylation is considered to be one of the most abundant post-translational modifications and is recognized for playing key roles in cellular functions. 28188526 2 49 link N-linked 319:326 arg1 glycosylation 328:340 Aberrant N-linked glycosylation 310:340 Aberrant N-linked glycosylation 310:340 Aberrant N-linked glycosylation has been associated with several human diseases and has prompted the development and constant improvement of analytical tools to separate, characterize, and quantify glycoproteins in complex mixtures extracted from various biological samples (such as blood and tissue). 28188526 8 50 theme proteomics 1511:1520 arg1 approach 1522:1529 A bottom-up, tandem mass spectrometry-based proteomics approach 1467:1529 approach 1522:1529 A bottom-up, tandem mass spectrometry-based proteomics approach is used for protein identification and quantitation, and allows for screening glycoform-specific changes across hundreds of plasma proteins. 28188526 2 51 theme human 375:379 arg1 diseases 381:388 several human diseases 367:388 several human diseases 367:388 Aberrant N-linked glycosylation has been associated with several human diseases and has prompted the development and constant improvement of analytical tools to separate, characterize, and quantify glycoproteins in complex mixtures extracted from various biological samples (such as blood and tissue). 28188526 6 52 theme moderate- 1268:1276 arg1 identifications 1249:1263 protein identifications 1241:1263 protein identifications of moderate- to low-abundant proteins detectable in plasma 1241:1322 Reversed-phase chromatography prior to digestion is used for further fractionation, allowing for an increased number of protein identifications of moderate- to low-abundant proteins detectable in plasma. 28188526 5 53 theme glycosylation 1106:1118 arg1 types 1097:1101 specific types 1088:1101 specific types of glycosylation 1088:1118 Immunodepletion is used to remove highly abundant proteins from human plasma, followed by glycoform separation using multi-lectin affinity chromatography, in which specific lectins are chosen to capture and elute specific types of glycosylation. 28188526 8 54 theme spectrometry-based 1492:1509 arg1 approach 1522:1529 A bottom-up, tandem mass spectrometry-based proteomics approach 1467:1529 approach 1522:1529 A bottom-up, tandem mass spectrometry-based proteomics approach is used for protein identification and quantitation, and allows for screening glycoform-specific changes across hundreds of plasma proteins. 28188526 2 55 theme several 367:373 arg1 diseases 381:388 several human diseases 367:388 several human diseases 367:388 Aberrant N-linked glycosylation has been associated with several human diseases and has prompted the development and constant improvement of analytical tools to separate, characterize, and quantify glycoproteins in complex mixtures extracted from various biological samples (such as blood and tissue). 28188526 8 56 theme plasma 1655:1660 arg1 proteins 1662:1669 plasma proteins 1655:1669 plasma proteins 1655:1669 A bottom-up, tandem mass spectrometry-based proteomics approach is used for protein identification and quantitation, and allows for screening glycoform-specific changes across hundreds of plasma proteins. 28188526 7 57 dep samples 1429:1435 arg1 such 1438:1441 such 1438:1441 such 1438:1441 This method also incorporates isotopic labeling during alkylation for relative quantitation between two samples (such as a case and control). 28188526 5 58 theme specific 1088:1095 arg1 types 1097:1101 specific types 1088:1101 specific types of glycosylation 1088:1118 Immunodepletion is used to remove highly abundant proteins from human plasma, followed by glycoform separation using multi-lectin affinity chromatography, in which specific lectins are chosen to capture and elute specific types of glycosylation. 28188526 4 59 theme LC-MS/MS 843:850 arg1 analysis 852:859 LC-MS/MS analysis 843:859 LC-MS/MS analysis 843:859 Herein a method using multidimensional intact protein fractionation and LC-MS/MS analysis is described. 28188526 2 60 dep development 411:421 arg1 the 407:409 the 407:409 the 407:409 Aberrant N-linked glycosylation has been associated with several human diseases and has prompted the development and constant improvement of analytical tools to separate, characterize, and quantify glycoproteins in complex mixtures extracted from various biological samples (such as blood and tissue). 28188526 3 61 theme carbohydrate-binding 624:643 arg1 Lectins 612:618 Lectins 612:618 Lectins 612:618 Lectins, or carbohydrate-binding proteins, have been used as valuable tools for enriching for glycoproteins and selecting for specific types of glycosylation. 28188526 3 61 theme carbohydrate-binding 624:643 arg1 tools 682:686 valuable tools 673:686 valuable tools for enriching for glycoproteins and selecting for specific types of glycosylation 673:768 Lectins, or carbohydrate-binding proteins, have been used as valuable tools for enriching for glycoproteins and selecting for specific types of glycosylation. 28188526 3 61 theme carbohydrate-binding 624:643 arg1 proteins 645:652 carbohydrate-binding proteins 624:652 carbohydrate-binding proteins 624:652 Lectins, or carbohydrate-binding proteins, have been used as valuable tools for enriching for glycoproteins and selecting for specific types of glycosylation. 28188526 6 62 from plasma 1317:1322 arg1 detectable 1303:1312 detectable 1303:1312 detectable 1303:1312 Reversed-phase chromatography prior to digestion is used for further fractionation, allowing for an increased number of protein identifications of moderate- to low-abundant proteins detectable in plasma. 28188526 3 63 gly glycoproteins 706:718 arg1 glycoproteins 706:718 glycoproteins 706:718 glycoproteins 706:718 Lectins, or carbohydrate-binding proteins, have been used as valuable tools for enriching for glycoproteins and selecting for specific types of glycosylation. 28188526 5 64 used used 894:897 arg2 Immunodepletion 875:889 Immunodepletion 875:889 Immunodepletion 875:889 Immunodepletion is used to remove highly abundant proteins from human plasma, followed by glycoform separation using multi-lectin affinity chromatography, in which specific lectins are chosen to capture and elute specific types of glycosylation. 28188526 5 65 theme glycoform 965:973 arg1 separation 975:984 glycoform separation 965:984 glycoform separation using multi-lectin affinity chromatography 965:1027 Immunodepletion is used to remove highly abundant proteins from human plasma, followed by glycoform separation using multi-lectin affinity chromatography, in which specific lectins are chosen to capture and elute specific types of glycosylation. 28188526 4 66 theme intact 810:815 arg1 fractionation 825:837 multidimensional intact protein fractionation 793:837 multidimensional intact protein fractionation 793:837 Herein a method using multidimensional intact protein fractionation and LC-MS/MS analysis is described. 28188526 1 67 theme Protein 147:153 arg1 glycosylation 155:167 Protein glycosylation 147:167 Protein glycosylation 147:167 Protein glycosylation is considered to be one of the most abundant post-translational modifications and is recognized for playing key roles in cellular functions. 28188526 8 68 used used 1534:1537 arg2 approach 1522:1529 A bottom-up, tandem mass spectrometry-based proteomics approach 1467:1529 approach 1522:1529 A bottom-up, tandem mass spectrometry-based proteomics approach is used for protein identification and quantitation, and allows for screening glycoform-specific changes across hundreds of plasma proteins. 28188526 6 69 from detectable 1303:1312 arg1 plasma 1317:1322 plasma 1317:1322 plasma 1317:1322 Reversed-phase chromatography prior to digestion is used for further fractionation, allowing for an increased number of protein identifications of moderate- to low-abundant proteins detectable in plasma. 28188526 7 70 dep case 1448:1451 arg1 a 1446:1446 a 1446:1446 a 1446:1446 This method also incorporates isotopic labeling during alkylation for relative quantitation between two samples (such as a case and control). 28188526 7 71 theme isotopic 1355:1362 arg1 labeling 1364:1371 isotopic labeling 1355:1371 isotopic labeling 1355:1371 This method also incorporates isotopic labeling during alkylation for relative quantitation between two samples (such as a case and control). 28188526 8 72 theme glycoform-specific 1609:1626 arg1 changes 1628:1634 glycoform-specific changes 1609:1634 glycoform-specific changes 1609:1634 A bottom-up, tandem mass spectrometry-based proteomics approach is used for protein identification and quantitation, and allows for screening glycoform-specific changes across hundreds of plasma proteins. 28188526 6 73 theme low-abundant 1281:1292 arg1 proteins 1294:1301 low-abundant proteins 1281:1301 low-abundant proteins detectable in plasma 1281:1322 Reversed-phase chromatography prior to digestion is used for further fractionation, allowing for an increased number of protein identifications of moderate- to low-abundant proteins detectable in plasma. 28188526 6 74 theme further 1182:1188 arg1 fractionation 1190:1202 further fractionation 1182:1202 further fractionation 1182:1202 Reversed-phase chromatography prior to digestion is used for further fractionation, allowing for an increased number of protein identifications of moderate- to low-abundant proteins detectable in plasma. 28188526 2 75 theme biological 565:574 arg1 samples 576:582 various biological samples 557:582 various biological samples (such as blood and tissue) 557:609 Aberrant N-linked glycosylation has been associated with several human diseases and has prompted the development and constant improvement of analytical tools to separate, characterize, and quantify glycoproteins in complex mixtures extracted from various biological samples (such as blood and tissue). 28059703 6 0 theme glutaminolysis 1122:1135 arg1 function 1087:1094 a primary function 1077:1094 a primary function of aerobic glycolysis and glutaminolysis 1077:1135 Thus, a primary function of aerobic glycolysis and glutaminolysis is to co-operatively limit metabolite supply to N-glycan biosynthesis, an activity with widespread implications for autoimmunity and cancer. 28059703 4 1 from biosynthesis 771:782 arg1 blasts 823:828 mouse T cell blasts 810:828 mouse T cell blasts 810:828 Here, we report that aerobic glycolysis and glutaminolysis co-operatively reduce UDP-GlcNAc biosynthesis and N-glycan branching in mouse T cell blasts by starving the hexosamine pathway of glucose and glutamine. 28059703 0 2 theme metabolite 80:89 arg1 supply 91:96 metabolite supply 80:96 metabolite supply to N-glycosylation 80:115 Glycolysis and glutaminolysis cooperatively control T cell function by limiting metabolite supply to N-glycosylation. 28059703 1 3 theme aerobic 187:193 arg1 glycolysis 195:204 aerobic glycolysis 187:204 aerobic glycolysis 187:204 Rapidly proliferating cells switch from oxidative phosphorylation to aerobic glycolysis plus glutaminolysis, markedly increasing glucose and glutamine catabolism. 28059703 6 4 with activity 1211:1218 arg1 implications 1236:1247 widespread implications 1225:1247 widespread implications for autoimmunity and cancer 1225:1275 Thus, a primary function of aerobic glycolysis and glutaminolysis is to co-operatively limit metabolite supply to N-glycan biosynthesis, an activity with widespread implications for autoimmunity and cancer. 28059703 3 5 theme receptor 574:581 arg1 endocytosis 583:593 receptor endocytosis 574:593 receptor endocytosis 574:593 The hexosamine biosynthetic pathway requires glucose and glutamine for de novo synthesis of UDP-GlcNAc, a sugar-nucleotide that inhibits receptor endocytosis and signaling by promoting N-acetylglucosamine branching of Asn (N)-linked glycans. 28059703 2 6 theme cancer 341:346 arg1 cells 348:352 cancer cells 341:352 cancer cells 341:352 Although Otto Warburg first described aerobic glycolysis in cancer cells >90 years ago, the primary purpose of this metabolic switch remains controversial. 28059703 6 7 theme widespread 1225:1234 arg1 implications 1236:1247 widespread implications 1225:1247 widespread implications for autoimmunity and cancer 1225:1275 Thus, a primary function of aerobic glycolysis and glutaminolysis is to co-operatively limit metabolite supply to N-glycan biosynthesis, an activity with widespread implications for autoimmunity and cancer. 28059703 5 8 theme endocytic 1029:1037 arg1 loss 1039:1042 endocytic loss 1029:1042 endocytic loss of IL-2 receptor-α (CD25) 1029:1068 This drives growth and pro-inflammatory TH17 over anti-inflammatory-induced T regulatory (iTreg) differentiation, the latter by promoting endocytic loss of IL-2 receptor-α (CD25). 28059703 4 9 theme glucose 868:874 arg1 pathway 857:863 the hexosamine pathway 842:863 the hexosamine pathway of glucose and glutamine 842:888 Here, we report that aerobic glycolysis and glutaminolysis co-operatively reduce UDP-GlcNAc biosynthesis and N-glycan branching in mouse T cell blasts by starving the hexosamine pathway of glucose and glutamine. 28059703 5 10 theme pro-inflammatory 914:929 arg1 differentiation 988:1002 pro-inflammatory TH17 over anti-inflammatory-induced T regulatory (iTreg) differentiation 914:1002 pro-inflammatory TH17 over anti-inflammatory-induced T regulatory (iTreg) differentiation 914:1002 This drives growth and pro-inflammatory TH17 over anti-inflammatory-induced T regulatory (iTreg) differentiation, the latter by promoting endocytic loss of IL-2 receptor-α (CD25). 28059703 6 11 theme aerobic 1099:1105 arg1 glycolysis 1107:1116 aerobic glycolysis 1099:1116 aerobic glycolysis 1099:1116 Thus, a primary function of aerobic glycolysis and glutaminolysis is to co-operatively limit metabolite supply to N-glycan biosynthesis, an activity with widespread implications for autoimmunity and cancer. 28059703 5 12 theme anti-inflammatory-induced 941:965 arg1 differentiation 988:1002 pro-inflammatory TH17 over anti-inflammatory-induced T regulatory (iTreg) differentiation 914:1002 pro-inflammatory TH17 over anti-inflammatory-induced T regulatory (iTreg) differentiation 914:1002 This drives growth and pro-inflammatory TH17 over anti-inflammatory-induced T regulatory (iTreg) differentiation, the latter by promoting endocytic loss of IL-2 receptor-α (CD25). 28059703 0 13 theme cell 54:57 arg1 function 59:66 T cell function 52:66 T cell function 52:66 Glycolysis and glutaminolysis cooperatively control T cell function by limiting metabolite supply to N-glycosylation. 28059703 2 14 theme aerobic 319:325 arg1 glycolysis 327:336 aerobic glycolysis 319:336 aerobic glycolysis in cancer cells 319:352 Although Otto Warburg first described aerobic glycolysis in cancer cells >90 years ago, the primary purpose of this metabolic switch remains controversial. 28059703 5 15 theme T 967:967 arg1 differentiation 988:1002 pro-inflammatory TH17 over anti-inflammatory-induced T regulatory (iTreg) differentiation 914:1002 pro-inflammatory TH17 over anti-inflammatory-induced T regulatory (iTreg) differentiation 914:1002 This drives growth and pro-inflammatory TH17 over anti-inflammatory-induced T regulatory (iTreg) differentiation, the latter by promoting endocytic loss of IL-2 receptor-α (CD25). 28059703 6 16 theme metabolite 1164:1173 arg1 supply 1175:1180 metabolite supply 1164:1180 metabolite supply 1164:1180 Thus, a primary function of aerobic glycolysis and glutaminolysis is to co-operatively limit metabolite supply to N-glycan biosynthesis, an activity with widespread implications for autoimmunity and cancer. 28059703 4 17 theme cell 818:821 arg1 blasts 823:828 mouse T cell blasts 810:828 mouse T cell blasts 810:828 Here, we report that aerobic glycolysis and glutaminolysis co-operatively reduce UDP-GlcNAc biosynthesis and N-glycan branching in mouse T cell blasts by starving the hexosamine pathway of glucose and glutamine. 28059703 5 18 theme regulatory 969:978 arg1 differentiation 988:1002 pro-inflammatory TH17 over anti-inflammatory-induced T regulatory (iTreg) differentiation 914:1002 pro-inflammatory TH17 over anti-inflammatory-induced T regulatory (iTreg) differentiation 914:1002 This drives growth and pro-inflammatory TH17 over anti-inflammatory-induced T regulatory (iTreg) differentiation, the latter by promoting endocytic loss of IL-2 receptor-α (CD25). 28059703 4 19 theme T 816:816 arg1 blasts 823:828 mouse T cell blasts 810:828 mouse T cell blasts 810:828 Here, we report that aerobic glycolysis and glutaminolysis co-operatively reduce UDP-GlcNAc biosynthesis and N-glycan branching in mouse T cell blasts by starving the hexosamine pathway of glucose and glutamine. 28059703 5 20 theme TH17 931:934 arg1 differentiation 988:1002 pro-inflammatory TH17 over anti-inflammatory-induced T regulatory (iTreg) differentiation 914:1002 pro-inflammatory TH17 over anti-inflammatory-induced T regulatory (iTreg) differentiation 914:1002 This drives growth and pro-inflammatory TH17 over anti-inflammatory-induced T regulatory (iTreg) differentiation, the latter by promoting endocytic loss of IL-2 receptor-α (CD25). 28059703 4 21 theme glutamine 880:888 arg1 pathway 857:863 the hexosamine pathway 842:863 the hexosamine pathway of glucose and glutamine 842:888 Here, we report that aerobic glycolysis and glutaminolysis co-operatively reduce UDP-GlcNAc biosynthesis and N-glycan branching in mouse T cell blasts by starving the hexosamine pathway of glucose and glutamine. 28059703 3 22 theme N-acetylglucosamine 622:640 arg1 branching 642:650 N-acetylglucosamine branching 622:650 N-acetylglucosamine branching of Asn (N)-linked glycans 622:676 The hexosamine biosynthetic pathway requires glucose and glutamine for de novo synthesis of UDP-GlcNAc, a sugar-nucleotide that inhibits receptor endocytosis and signaling by promoting N-acetylglucosamine branching of Asn (N)-linked glycans. 28059703 3 23 link -linked 662:668 arg1 glycans 670:676 Asn (N)-linked glycans 655:676 Asn (N)-linked glycans 655:676 The hexosamine biosynthetic pathway requires glucose and glutamine for de novo synthesis of UDP-GlcNAc, a sugar-nucleotide that inhibits receptor endocytosis and signaling by promoting N-acetylglucosamine branching of Asn (N)-linked glycans. 28059703 5 24 theme IL-2 1047:1050 arg1 CD25 1064:1067 CD25 1064:1067 CD25 1064:1067 This drives growth and pro-inflammatory TH17 over anti-inflammatory-induced T regulatory (iTreg) differentiation, the latter by promoting endocytic loss of IL-2 receptor-α (CD25). 28059703 5 24 theme IL-2 1047:1050 arg1 receptor-α 1052:1061 IL-2 receptor-α 1047:1061 IL-2 receptor-α (CD25) 1047:1068 This drives growth and pro-inflammatory TH17 over anti-inflammatory-induced T regulatory (iTreg) differentiation, the latter by promoting endocytic loss of IL-2 receptor-α (CD25). 28059703 1 25 theme increasing 236:245 arg1 glucose 247:253 markedly increasing glucose 227:253 markedly increasing glucose 227:253 Rapidly proliferating cells switch from oxidative phosphorylation to aerobic glycolysis plus glutaminolysis, markedly increasing glucose and glutamine catabolism. 28059703 0 26 theme T 52:52 arg1 function 59:66 T cell function 52:66 T cell function 52:66 Glycolysis and glutaminolysis cooperatively control T cell function by limiting metabolite supply to N-glycosylation. 28059703 4 27 theme N-glycan 788:795 arg1 branching 797:805 N-glycan branching 788:805 N-glycan branching 788:805 Here, we report that aerobic glycolysis and glutaminolysis co-operatively reduce UDP-GlcNAc biosynthesis and N-glycan branching in mouse T cell blasts by starving the hexosamine pathway of glucose and glutamine. 28059703 4 28 theme aerobic 700:706 arg1 glycolysis 708:717 aerobic glycolysis 700:717 aerobic glycolysis 700:717 Here, we report that aerobic glycolysis and glutaminolysis co-operatively reduce UDP-GlcNAc biosynthesis and N-glycan branching in mouse T cell blasts by starving the hexosamine pathway of glucose and glutamine. 28059703 3 29 theme de 508:509 arg1 synthesis 516:524 de novo synthesis 508:524 de novo synthesis of UDP-GlcNAc, a sugar-nucleotide that inhibits receptor endocytosis and signaling by promoting N-acetylglucosamine branching of Asn (N)-linked glycans 508:676 The hexosamine biosynthetic pathway requires glucose and glutamine for de novo synthesis of UDP-GlcNAc, a sugar-nucleotide that inhibits receptor endocytosis and signaling by promoting N-acetylglucosamine branching of Asn (N)-linked glycans. 28059703 4 30 theme UDP-GlcNAc 760:769 arg1 biosynthesis 771:782 UDP-GlcNAc biosynthesis 760:782 UDP-GlcNAc biosynthesis 760:782 Here, we report that aerobic glycolysis and glutaminolysis co-operatively reduce UDP-GlcNAc biosynthesis and N-glycan branching in mouse T cell blasts by starving the hexosamine pathway of glucose and glutamine. 28059703 3 31 theme -linked 662:668 arg1 glycans 670:676 Asn (N)-linked glycans 655:676 Asn (N)-linked glycans 655:676 The hexosamine biosynthetic pathway requires glucose and glutamine for de novo synthesis of UDP-GlcNAc, a sugar-nucleotide that inhibits receptor endocytosis and signaling by promoting N-acetylglucosamine branching of Asn (N)-linked glycans. 28059703 5 32 theme over 936:939 arg1 differentiation 988:1002 pro-inflammatory TH17 over anti-inflammatory-induced T regulatory (iTreg) differentiation 914:1002 pro-inflammatory TH17 over anti-inflammatory-induced T regulatory (iTreg) differentiation 914:1002 This drives growth and pro-inflammatory TH17 over anti-inflammatory-induced T regulatory (iTreg) differentiation, the latter by promoting endocytic loss of IL-2 receptor-α (CD25). 28059703 3 33 theme hexosamine 441:450 arg1 pathway 465:471 The hexosamine biosynthetic pathway 437:471 The hexosamine biosynthetic pathway 437:471 The hexosamine biosynthetic pathway requires glucose and glutamine for de novo synthesis of UDP-GlcNAc, a sugar-nucleotide that inhibits receptor endocytosis and signaling by promoting N-acetylglucosamine branching of Asn (N)-linked glycans. 28059703 5 34 theme iTreg 981:985 arg1 differentiation 988:1002 pro-inflammatory TH17 over anti-inflammatory-induced T regulatory (iTreg) differentiation 914:1002 pro-inflammatory TH17 over anti-inflammatory-induced T regulatory (iTreg) differentiation 914:1002 This drives growth and pro-inflammatory TH17 over anti-inflammatory-induced T regulatory (iTreg) differentiation, the latter by promoting endocytic loss of IL-2 receptor-α (CD25). 28059703 1 35 theme proliferating 126:138 arg1 cells 140:144 Rapidly proliferating cells 118:144 Rapidly proliferating cells 118:144 Rapidly proliferating cells switch from oxidative phosphorylation to aerobic glycolysis plus glutaminolysis, markedly increasing glucose and glutamine catabolism. 28059703 3 36 theme biosynthetic 452:463 arg1 pathway 465:471 The hexosamine biosynthetic pathway 437:471 The hexosamine biosynthetic pathway 437:471 The hexosamine biosynthetic pathway requires glucose and glutamine for de novo synthesis of UDP-GlcNAc, a sugar-nucleotide that inhibits receptor endocytosis and signaling by promoting N-acetylglucosamine branching of Asn (N)-linked glycans. 28059703 2 37 theme primary 373:379 arg1 purpose 381:387 the primary purpose 369:387 the primary purpose of this metabolic switch 369:412 Although Otto Warburg first described aerobic glycolysis in cancer cells >90 years ago, the primary purpose of this metabolic switch remains controversial. 28059703 2 38 from glycolysis 327:336 arg1 cells 348:352 cancer cells 341:352 cancer cells 341:352 Although Otto Warburg first described aerobic glycolysis in cancer cells >90 years ago, the primary purpose of this metabolic switch remains controversial. 28059703 1 39 theme oxidative 158:166 arg1 phosphorylation 168:182 oxidative phosphorylation 158:182 oxidative phosphorylation 158:182 Rapidly proliferating cells switch from oxidative phosphorylation to aerobic glycolysis plus glutaminolysis, markedly increasing glucose and glutamine catabolism. 28059703 3 40 dep de 508:509 arg1 novo 511:514 novo 511:514 novo 511:514 The hexosamine biosynthetic pathway requires glucose and glutamine for de novo synthesis of UDP-GlcNAc, a sugar-nucleotide that inhibits receptor endocytosis and signaling by promoting N-acetylglucosamine branching of Asn (N)-linked glycans. 28059703 3 41 theme UDP-GlcNAc 529:538 arg1 synthesis 516:524 de novo synthesis 508:524 de novo synthesis of UDP-GlcNAc, a sugar-nucleotide that inhibits receptor endocytosis and signaling by promoting N-acetylglucosamine branching of Asn (N)-linked glycans 508:676 The hexosamine biosynthetic pathway requires glucose and glutamine for de novo synthesis of UDP-GlcNAc, a sugar-nucleotide that inhibits receptor endocytosis and signaling by promoting N-acetylglucosamine branching of Asn (N)-linked glycans. 28059703 1 42 theme glutamine 259:267 arg1 catabolism 269:278 glutamine catabolism 259:278 glutamine catabolism 259:278 Rapidly proliferating cells switch from oxidative phosphorylation to aerobic glycolysis plus glutaminolysis, markedly increasing glucose and glutamine catabolism. 28059703 4 43 theme hexosamine 846:855 arg1 pathway 857:863 the hexosamine pathway 842:863 the hexosamine pathway of glucose and glutamine 842:888 Here, we report that aerobic glycolysis and glutaminolysis co-operatively reduce UDP-GlcNAc biosynthesis and N-glycan branching in mouse T cell blasts by starving the hexosamine pathway of glucose and glutamine. 28059703 5 44 theme receptor-α 1052:1061 arg1 loss 1039:1042 endocytic loss 1029:1042 endocytic loss of IL-2 receptor-α (CD25) 1029:1068 This drives growth and pro-inflammatory TH17 over anti-inflammatory-induced T regulatory (iTreg) differentiation, the latter by promoting endocytic loss of IL-2 receptor-α (CD25). 28059703 6 45 theme N-glycan 1185:1192 arg1 biosynthesis 1194:1205 N-glycan biosynthesis 1185:1205 N-glycan biosynthesis 1185:1205 Thus, a primary function of aerobic glycolysis and glutaminolysis is to co-operatively limit metabolite supply to N-glycan biosynthesis, an activity with widespread implications for autoimmunity and cancer. 28059703 6 45 theme N-glycan 1185:1192 arg1 activity 1211:1218 an activity 1208:1218 an activity with widespread implications for autoimmunity and cancer 1208:1275 Thus, a primary function of aerobic glycolysis and glutaminolysis is to co-operatively limit metabolite supply to N-glycan biosynthesis, an activity with widespread implications for autoimmunity and cancer. 28059703 4 46 from branching 797:805 arg1 blasts 823:828 mouse T cell blasts 810:828 mouse T cell blasts 810:828 Here, we report that aerobic glycolysis and glutaminolysis co-operatively reduce UDP-GlcNAc biosynthesis and N-glycan branching in mouse T cell blasts by starving the hexosamine pathway of glucose and glutamine. 28059703 4 47 theme mouse 810:814 arg1 blasts 823:828 mouse T cell blasts 810:828 mouse T cell blasts 810:828 Here, we report that aerobic glycolysis and glutaminolysis co-operatively reduce UDP-GlcNAc biosynthesis and N-glycan branching in mouse T cell blasts by starving the hexosamine pathway of glucose and glutamine. 28059703 6 48 theme glycolysis 1107:1116 arg1 function 1087:1094 a primary function 1077:1094 a primary function of aerobic glycolysis and glutaminolysis 1077:1135 Thus, a primary function of aerobic glycolysis and glutaminolysis is to co-operatively limit metabolite supply to N-glycan biosynthesis, an activity with widespread implications for autoimmunity and cancer. 28059703 3 49 theme glycans 670:676 arg1 branching 642:650 N-acetylglucosamine branching 622:650 N-acetylglucosamine branching of Asn (N)-linked glycans 622:676 The hexosamine biosynthetic pathway requires glucose and glutamine for de novo synthesis of UDP-GlcNAc, a sugar-nucleotide that inhibits receptor endocytosis and signaling by promoting N-acetylglucosamine branching of Asn (N)-linked glycans. 28059703 2 50 theme switch 407:412 arg1 purpose 381:387 the primary purpose 369:387 the primary purpose of this metabolic switch 369:412 Although Otto Warburg first described aerobic glycolysis in cancer cells >90 years ago, the primary purpose of this metabolic switch remains controversial. 28059703 2 51 theme Otto 290:293 arg1 Warburg 295:301 Otto Warburg 290:301 Otto Warburg 290:301 Although Otto Warburg first described aerobic glycolysis in cancer cells >90 years ago, the primary purpose of this metabolic switch remains controversial. 28059703 2 52 theme metabolic 397:405 arg1 switch 407:412 this metabolic switch 392:412 this metabolic switch 392:412 Although Otto Warburg first described aerobic glycolysis in cancer cells >90 years ago, the primary purpose of this metabolic switch remains controversial. 28059703 6 53 theme primary 1079:1085 arg1 function 1087:1094 a primary function 1077:1094 a primary function of aerobic glycolysis and glutaminolysis 1077:1135 Thus, a primary function of aerobic glycolysis and glutaminolysis is to co-operatively limit metabolite supply to N-glycan biosynthesis, an activity with widespread implications for autoimmunity and cancer. 27001651 9 0 theme MAb 971:973 arg1 COS3A 975:979 RESULTS MAb COS3A 963:979 RESULTS MAb COS3A 963:979 RESULTS MAb COS3A bound specifically to a molecule expressed on the surface of various human hematopoietic cells and cell lines but not on erythrocytes. 27001651 13 1 theme CD63 1477:1480 arg1 molecule 1482:1489 the CD63 molecule 1473:1489 the CD63 molecule 1473:1489 CONCLUSIONS The mAb COS3A recognized the CD63 molecule and strongly diminished granulocyte phagocytosis of E. coli, suggesting that CD63 may play a crucial role in the initial step of phagocytosis. 27001651 10 2 theme N-linked 1211:1218 arg1 glycan 1220:1225 N-linked glycan 1211:1225 N-linked glycan 1211:1225 The antigen had a molecular weight of 30-70 kDa, which was reduced to 25 kDa by elimination of N-linked glycan. 27001651 13 3 dep CONCLUSIONS 1436:1446 arg1 recognized 1462:1471 recognized 1462:1471 recognized 1462:1471 CONCLUSIONS The mAb COS3A recognized the CD63 molecule and strongly diminished granulocyte phagocytosis of E. coli, suggesting that CD63 may play a crucial role in the initial step of phagocytosis. 27001651 7 4 from presence 807:814 arg1 treatment 734:742 N-glycosidase F treatment 718:742 N-glycosidase F treatment of COS3A-precipitated protein and culture of U937 cells in the presence of tunicamycin before cell lysate preparation 718:860 N-glycosidase F treatment of COS3A-precipitated protein and culture of U937 cells in the presence of tunicamycin before cell lysate preparation were used to study the glycosylation state of proteins. 27001651 7 5 theme glycosylation 885:897 arg1 state 899:903 the glycosylation state 881:903 the glycosylation state of proteins 881:915 N-glycosidase F treatment of COS3A-precipitated protein and culture of U937 cells in the presence of tunicamycin before cell lysate preparation were used to study the glycosylation state of proteins. 27001651 7 6 theme COS3A-precipitated 747:764 arg1 protein 766:772 COS3A-precipitated protein 747:772 COS3A-precipitated protein 747:772 N-glycosidase F treatment of COS3A-precipitated protein and culture of U937 cells in the presence of tunicamycin before cell lysate preparation were used to study the glycosylation state of proteins. 27001651 10 7 theme glycan 1220:1225 arg1 elimination 1196:1206 elimination 1196:1206 elimination of N-linked glycan 1196:1225 The antigen had a molecular weight of 30-70 kDa, which was reduced to 25 kDa by elimination of N-linked glycan. 27001651 2 8 theme leukocyte 258:266 arg1 molecules 276:284 leukocyte surface molecules 258:284 leukocyte surface molecules 258:284 Several mAbs against leukocyte surface molecules have been generated in our laboratory. 27001651 1 9 theme science 165:171 arg1 research 173:180 life science research 160:180 life science research 160:180 BACKGROUND Monoclonal antibodies (mAbs) have become essential tools in life science research and in medicine, because of their extreme specificity. 27001651 10 10 theme kDa 1160:1162 arg1 weight 1144:1149 a molecular weight 1132:1149 a molecular weight 1132:1149 The antigen had a molecular weight of 30-70 kDa, which was reduced to 25 kDa by elimination of N-linked glycan. 27001651 6 11 theme COS3A 617:621 arg1 target 607:612 the molecular target 593:612 the molecular target of COS3A 593:621 Biochemical characterization of the molecular target of COS3A was approached by immunoprecipitation, Western blotting and amino acid sequencing using LC-MS. 27001651 7 12 used used 867:870 arg2 treatment 734:742 N-glycosidase F treatment 718:742 N-glycosidase F treatment of COS3A-precipitated protein and culture of U937 cells in the presence of tunicamycin before cell lysate preparation 718:860 N-glycosidase F treatment of COS3A-precipitated protein and culture of U937 cells in the presence of tunicamycin before cell lysate preparation were used to study the glycosylation state of proteins. 27001651 6 13 theme target 607:612 arg1 characterization 573:588 Biochemical characterization 561:588 Biochemical characterization of the molecular target of COS3A 561:621 Biochemical characterization of the molecular target of COS3A was approached by immunoprecipitation, Western blotting and amino acid sequencing using LC-MS. 27001651 7 14 theme F 732:732 arg1 treatment 734:742 N-glycosidase F treatment 718:742 N-glycosidase F treatment of COS3A-precipitated protein and culture of U937 cells in the presence of tunicamycin before cell lysate preparation 718:860 N-glycosidase F treatment of COS3A-precipitated protein and culture of U937 cells in the presence of tunicamycin before cell lysate preparation were used to study the glycosylation state of proteins. 27001651 13 15 theme phagocytosis 1620:1631 arg1 step 1612:1615 the initial step 1600:1615 the initial step of phagocytosis 1600:1631 CONCLUSIONS The mAb COS3A recognized the CD63 molecule and strongly diminished granulocyte phagocytosis of E. coli, suggesting that CD63 may play a crucial role in the initial step of phagocytosis. 27001651 7 16 from protein 766:772 arg1 presence 807:814 the presence 803:814 the presence of tunicamycin 803:829 N-glycosidase F treatment of COS3A-precipitated protein and culture of U937 cells in the presence of tunicamycin before cell lysate preparation were used to study the glycosylation state of proteins. 27001651 6 17 theme amino 683:687 arg1 sequencing 694:703 amino acid sequencing 683:703 amino acid sequencing 683:703 Biochemical characterization of the molecular target of COS3A was approached by immunoprecipitation, Western blotting and amino acid sequencing using LC-MS. 27001651 14 18 theme further 1741:1747 arg1 study 1749:1753 further study 1741:1753 further study of the mechanism of phagocytosis 1741:1786 MAb COS3A is, therefore, suitable for both biochemical and functional studies of CD63, and may be used for further study of the mechanism of phagocytosis and also in therapeutic approaches. 27001651 5 19 theme flow 545:548 arg1 cytometry 550:558 flow cytometry 545:558 flow cytometry 545:558 METHOD Cellular distribution was analyzed by immunofluorescence staining and flow cytometry. 27001651 7 20 from culture 778:784 arg1 presence 807:814 the presence 803:814 the presence of tunicamycin 803:829 N-glycosidase F treatment of COS3A-precipitated protein and culture of U937 cells in the presence of tunicamycin before cell lysate preparation were used to study the glycosylation state of proteins. 27001651 9 21 theme various 1042:1048 arg1 cells 1070:1074 various human hematopoietic cells 1042:1074 various human hematopoietic cells 1042:1074 RESULTS MAb COS3A bound specifically to a molecule expressed on the surface of various human hematopoietic cells and cell lines but not on erythrocytes. 27001651 14 22 theme CD63 1715:1718 arg1 studies 1704:1710 both biochemical and functional studies 1672:1710 both biochemical and functional studies of CD63 1672:1718 MAb COS3A is, therefore, suitable for both biochemical and functional studies of CD63, and may be used for further study of the mechanism of phagocytosis and also in therapeutic approaches. 27001651 7 23 gly glycosylation 885:897 arg1 proteins 908:915 proteins 908:915 proteins 908:915 N-glycosidase F treatment of COS3A-precipitated protein and culture of U937 cells in the presence of tunicamycin before cell lysate preparation were used to study the glycosylation state of proteins. 27001651 9 24 theme hematopoietic 1056:1068 arg1 cells 1070:1074 various human hematopoietic cells 1042:1074 various human hematopoietic cells 1042:1074 RESULTS MAb COS3A bound specifically to a molecule expressed on the surface of various human hematopoietic cells and cell lines but not on erythrocytes. 27001651 6 25 theme Western 662:668 arg1 blotting 670:677 Western blotting 662:677 Western blotting 662:677 Biochemical characterization of the molecular target of COS3A was approached by immunoprecipitation, Western blotting and amino acid sequencing using LC-MS. 27001651 0 26 theme novel 48:52 arg1 COS3A 39:43 COS3A 39:43 COS3A 39:43 Biochemical and functional analysis of COS3A, a novel CD63-specific monoclonal antibody. 27001651 0 26 theme novel 48:52 arg1 antibody 79:86 a novel CD63-specific monoclonal antibody 46:86 a novel CD63-specific monoclonal antibody 46:86 Biochemical and functional analysis of COS3A, a novel CD63-specific monoclonal antibody. 27001651 1 27 theme essential 141:149 arg1 tools 151:155 essential tools 141:155 essential tools in life science research and in medicine 141:196 BACKGROUND Monoclonal antibodies (mAbs) have become essential tools in life science research and in medicine, because of their extreme specificity. 27001651 9 28 theme lines 1085:1089 arg1 surface 1031:1037 the surface 1027:1037 the surface of various human hematopoietic cells and cell lines 1027:1089 RESULTS MAb COS3A bound specifically to a molecule expressed on the surface of various human hematopoietic cells and cell lines but not on erythrocytes. 27001651 0 29 theme monoclonal 68:77 arg1 COS3A 39:43 COS3A 39:43 COS3A 39:43 Biochemical and functional analysis of COS3A, a novel CD63-specific monoclonal antibody. 27001651 0 29 theme monoclonal 68:77 arg1 antibody 79:86 a novel CD63-specific monoclonal antibody 46:86 a novel CD63-specific monoclonal antibody 46:86 Biochemical and functional analysis of COS3A, a novel CD63-specific monoclonal antibody. 27001651 1 30 from tools 151:155 arg1 research 173:180 life science research 160:180 life science research 160:180 BACKGROUND Monoclonal antibodies (mAbs) have become essential tools in life science research and in medicine, because of their extreme specificity. 27001651 1 30 from tools 151:155 arg1 medicine 189:196 medicine 189:196 medicine 189:196 BACKGROUND Monoclonal antibodies (mAbs) have become essential tools in life science research and in medicine, because of their extreme specificity. 27001651 10 31 theme molecular 1134:1142 arg1 weight 1144:1149 a molecular weight 1132:1149 a molecular weight 1132:1149 The antigen had a molecular weight of 30-70 kDa, which was reduced to 25 kDa by elimination of N-linked glycan. 27001651 5 32 theme Cellular 475:482 arg1 distribution 484:495 METHOD Cellular distribution 468:495 METHOD Cellular distribution 468:495 METHOD Cellular distribution was analyzed by immunofluorescence staining and flow cytometry. 27001651 13 33 theme coli 1546:1549 arg1 phagocytosis 1527:1538 strongly diminished granulocyte phagocytosis 1495:1538 strongly diminished granulocyte phagocytosis 1495:1538 CONCLUSIONS The mAb COS3A recognized the CD63 molecule and strongly diminished granulocyte phagocytosis of E. coli, suggesting that CD63 may play a crucial role in the initial step of phagocytosis. 27001651 13 33 theme coli 1546:1549 arg1 molecule 1482:1489 the CD63 molecule 1473:1489 the CD63 molecule 1473:1489 CONCLUSIONS The mAb COS3A recognized the CD63 molecule and strongly diminished granulocyte phagocytosis of E. coli, suggesting that CD63 may play a crucial role in the initial step of phagocytosis. 27001651 3 34 theme biochemical 364:374 arg1 analysis 391:398 biochemical and functional analysis 364:398 biochemical and functional analysis 364:398 From these, mAb COS3A was selected for biochemical and functional analysis. 27001651 0 35 theme Biochemical 0:10 arg1 analysis 27:34 Biochemical and functional analysis 0:34 Biochemical and functional analysis of COS3A, a novel CD63-specific monoclonal antibody 0:86 Biochemical and functional analysis of COS3A, a novel CD63-specific monoclonal antibody. 27001651 7 36 theme cell 838:841 arg1 preparation 850:860 cell lysate preparation 838:860 cell lysate preparation 838:860 N-glycosidase F treatment of COS3A-precipitated protein and culture of U937 cells in the presence of tunicamycin before cell lysate preparation were used to study the glycosylation state of proteins. 27001651 1 37 theme BACKGROUND 89:98 arg1 mAbs 123:126 mAbs 123:126 mAbs 123:126 BACKGROUND Monoclonal antibodies (mAbs) have become essential tools in life science research and in medicine, because of their extreme specificity. 27001651 1 37 theme BACKGROUND 89:98 arg1 antibodies 111:120 BACKGROUND Monoclonal antibodies 89:120 BACKGROUND Monoclonal antibodies (mAbs) 89:127 BACKGROUND Monoclonal antibodies (mAbs) have become essential tools in life science research and in medicine, because of their extreme specificity. 27001651 10 38 contain had 1128:1130 arg2 weight 1144:1149 a molecular weight 1132:1149 a molecular weight 1132:1149 The antigen had a molecular weight of 30-70 kDa, which was reduced to 25 kDa by elimination of N-linked glycan. 27001651 10 38 contain had 1128:1130 arg1 antigen 1120:1126 The antigen 1116:1126 The antigen 1116:1126 The antigen had a molecular weight of 30-70 kDa, which was reduced to 25 kDa by elimination of N-linked glycan. 27001651 13 39 theme granulocyte 1515:1525 arg1 phagocytosis 1527:1538 strongly diminished granulocyte phagocytosis 1495:1538 strongly diminished granulocyte phagocytosis 1495:1538 CONCLUSIONS The mAb COS3A recognized the CD63 molecule and strongly diminished granulocyte phagocytosis of E. coli, suggesting that CD63 may play a crucial role in the initial step of phagocytosis. 27001651 0 40 theme functional 16:25 arg1 analysis 27:34 Biochemical and functional analysis 0:34 Biochemical and functional analysis of COS3A, a novel CD63-specific monoclonal antibody 0:86 Biochemical and functional analysis of COS3A, a novel CD63-specific monoclonal antibody. 27001651 7 41 theme tunicamycin 819:829 arg1 presence 807:814 the presence 803:814 the presence of tunicamycin 803:829 N-glycosidase F treatment of COS3A-precipitated protein and culture of U937 cells in the presence of tunicamycin before cell lysate preparation were used to study the glycosylation state of proteins. 27001651 8 42 theme flow 947:950 arg1 cytometry 952:960 flow cytometry 947:960 flow cytometry 947:960 Phagocytosis was examined by flow cytometry. 27001651 6 43 theme acid 689:692 arg1 sequencing 694:703 amino acid sequencing 683:703 amino acid sequencing 683:703 Biochemical characterization of the molecular target of COS3A was approached by immunoprecipitation, Western blotting and amino acid sequencing using LC-MS. 27001651 3 44 theme functional 380:389 arg1 analysis 391:398 biochemical and functional analysis 364:398 biochemical and functional analysis 364:398 From these, mAb COS3A was selected for biochemical and functional analysis. 27001651 7 45 theme U937 789:792 arg1 cells 794:798 U937 cells 789:798 U937 cells 789:798 N-glycosidase F treatment of COS3A-precipitated protein and culture of U937 cells in the presence of tunicamycin before cell lysate preparation were used to study the glycosylation state of proteins. 27001651 14 46 used used 1732:1735 arg2 COS3A 1638:1642 MAb COS3A 1634:1642 MAb COS3A 1634:1642 MAb COS3A is, therefore, suitable for both biochemical and functional studies of CD63, and may be used for further study of the mechanism of phagocytosis and also in therapeutic approaches. 27001651 7 47 theme culture 778:784 arg1 treatment 734:742 N-glycosidase F treatment 718:742 N-glycosidase F treatment of COS3A-precipitated protein and culture of U937 cells in the presence of tunicamycin before cell lysate preparation 718:860 N-glycosidase F treatment of COS3A-precipitated protein and culture of U937 cells in the presence of tunicamycin before cell lysate preparation were used to study the glycosylation state of proteins. 27001651 10 48 link N-linked 1211:1218 arg1 glycan 1220:1225 N-linked glycan 1211:1225 N-linked glycan 1211:1225 The antigen had a molecular weight of 30-70 kDa, which was reduced to 25 kDa by elimination of N-linked glycan. 27001651 9 49 theme RESULTS 963:969 arg1 COS3A 975:979 RESULTS MAb COS3A 963:979 RESULTS MAb COS3A 963:979 RESULTS MAb COS3A bound specifically to a molecule expressed on the surface of various human hematopoietic cells and cell lines but not on erythrocytes. 27001651 7 50 theme protein 766:772 arg1 treatment 734:742 N-glycosidase F treatment 718:742 N-glycosidase F treatment of COS3A-precipitated protein and culture of U937 cells in the presence of tunicamycin before cell lysate preparation 718:860 N-glycosidase F treatment of COS3A-precipitated protein and culture of U937 cells in the presence of tunicamycin before cell lysate preparation were used to study the glycosylation state of proteins. 27001651 7 51 theme proteins 908:915 arg1 state 899:903 the glycosylation state 881:903 the glycosylation state of proteins 881:915 N-glycosidase F treatment of COS3A-precipitated protein and culture of U937 cells in the presence of tunicamycin before cell lysate preparation were used to study the glycosylation state of proteins. 27001651 2 52 theme surface 268:274 arg1 molecules 276:284 leukocyte surface molecules 258:284 leukocyte surface molecules 258:284 Several mAbs against leukocyte surface molecules have been generated in our laboratory. 27001651 1 53 theme life 160:163 arg1 research 173:180 life science research 160:180 life science research 160:180 BACKGROUND Monoclonal antibodies (mAbs) have become essential tools in life science research and in medicine, because of their extreme specificity. 27001651 13 54 theme initial 1604:1610 arg1 step 1612:1615 the initial step 1600:1615 the initial step of phagocytosis 1600:1631 CONCLUSIONS The mAb COS3A recognized the CD63 molecule and strongly diminished granulocyte phagocytosis of E. coli, suggesting that CD63 may play a crucial role in the initial step of phagocytosis. 27001651 12 55 theme granulocyte 1410:1420 arg1 phagocytosis 1422:1433 granulocyte phagocytosis 1410:1433 granulocyte phagocytosis 1410:1433 Remarkably, functional analysis demonstrated that mAb COS3A dramatically reduced granulocyte phagocytosis. 27001651 6 56 theme molecular 597:605 arg1 target 607:612 the molecular target 593:612 the molecular target of COS3A 593:621 Biochemical characterization of the molecular target of COS3A was approached by immunoprecipitation, Western blotting and amino acid sequencing using LC-MS. 27001651 13 57 theme mAb 1452:1454 arg1 COS3A 1456:1460 The mAb COS3A 1448:1460 The mAb COS3A 1448:1460 CONCLUSIONS The mAb COS3A recognized the CD63 molecule and strongly diminished granulocyte phagocytosis of E. coli, suggesting that CD63 may play a crucial role in the initial step of phagocytosis. 27001651 13 58 theme crucial 1584:1590 arg1 role 1592:1595 a crucial role 1582:1595 a crucial role 1582:1595 CONCLUSIONS The mAb COS3A recognized the CD63 molecule and strongly diminished granulocyte phagocytosis of E. coli, suggesting that CD63 may play a crucial role in the initial step of phagocytosis. 27001651 5 59 theme METHOD 468:473 arg1 distribution 484:495 METHOD Cellular distribution 468:495 METHOD Cellular distribution 468:495 METHOD Cellular distribution was analyzed by immunofluorescence staining and flow cytometry. 27001651 7 60 theme N-glycosidase 718:730 arg1 F 732:732 N-glycosidase F 718:732 N-glycosidase F treatment of COS3A-precipitated protein and culture of U937 cells in the presence of tunicamycin before cell lysate preparation 718:860 N-glycosidase F treatment of COS3A-precipitated protein and culture of U937 cells in the presence of tunicamycin before cell lysate preparation were used to study the glycosylation state of proteins. 27001651 12 61 theme mAb 1379:1381 arg1 COS3A 1383:1387 mAb COS3A 1379:1387 mAb COS3A 1379:1387 Remarkably, functional analysis demonstrated that mAb COS3A dramatically reduced granulocyte phagocytosis. 27001651 14 62 theme MAb 1634:1636 arg1 COS3A 1638:1642 MAb COS3A 1634:1642 MAb COS3A 1634:1642 MAb COS3A is, therefore, suitable for both biochemical and functional studies of CD63, and may be used for further study of the mechanism of phagocytosis and also in therapeutic approaches. 27001651 9 63 theme human 1050:1054 arg1 cells 1070:1074 various human hematopoietic cells 1042:1074 various human hematopoietic cells 1042:1074 RESULTS MAb COS3A bound specifically to a molecule expressed on the surface of various human hematopoietic cells and cell lines but not on erythrocytes. 27001651 9 64 theme cells 1070:1074 arg1 surface 1031:1037 the surface 1027:1037 the surface of various human hematopoietic cells and cell lines 1027:1089 RESULTS MAb COS3A bound specifically to a molecule expressed on the surface of various human hematopoietic cells and cell lines but not on erythrocytes. 27001651 0 65 theme CD63-specific 54:66 arg1 COS3A 39:43 COS3A 39:43 COS3A 39:43 Biochemical and functional analysis of COS3A, a novel CD63-specific monoclonal antibody. 27001651 0 65 theme CD63-specific 54:66 arg1 antibody 79:86 a novel CD63-specific monoclonal antibody 46:86 a novel CD63-specific monoclonal antibody 46:86 Biochemical and functional analysis of COS3A, a novel CD63-specific monoclonal antibody. 27001651 14 66 theme functional 1693:1702 arg1 studies 1704:1710 both biochemical and functional studies 1672:1710 both biochemical and functional studies of CD63 1672:1718 MAb COS3A is, therefore, suitable for both biochemical and functional studies of CD63, and may be used for further study of the mechanism of phagocytosis and also in therapeutic approaches. 27001651 2 67 theme Several 237:243 arg1 mAbs 245:248 Several mAbs 237:248 Several mAbs against leukocyte surface molecules 237:284 Several mAbs against leukocyte surface molecules have been generated in our laboratory. 27001651 5 68 theme immunofluorescence 513:530 arg1 staining 532:539 immunofluorescence staining 513:539 immunofluorescence staining 513:539 METHOD Cellular distribution was analyzed by immunofluorescence staining and flow cytometry. 27001651 12 69 theme functional 1341:1350 arg1 analysis 1352:1359 functional analysis 1341:1359 functional analysis 1341:1359 Remarkably, functional analysis demonstrated that mAb COS3A dramatically reduced granulocyte phagocytosis. 27001651 4 70 dep properties 426:435 arg1 the 422:424 the 422:424 the 422:424 OBJECTIVE To analyze the properties and function of the mAb COS3A. 27001651 9 71 theme cell 1080:1083 arg1 lines 1085:1089 cell lines 1080:1089 cell lines 1080:1089 RESULTS MAb COS3A bound specifically to a molecule expressed on the surface of various human hematopoietic cells and cell lines but not on erythrocytes. 27001651 14 72 theme biochemical 1677:1687 arg1 studies 1704:1710 both biochemical and functional studies 1672:1710 both biochemical and functional studies of CD63 1672:1718 MAb COS3A is, therefore, suitable for both biochemical and functional studies of CD63, and may be used for further study of the mechanism of phagocytosis and also in therapeutic approaches. 27001651 4 73 theme COS3A 461:465 arg1 function 441:448 function 441:448 function 441:448 OBJECTIVE To analyze the properties and function of the mAb COS3A. 27001651 4 73 theme COS3A 461:465 arg1 properties 426:435 properties 426:435 properties 426:435 OBJECTIVE To analyze the properties and function of the mAb COS3A. 27001651 3 74 theme mAb 337:339 arg1 COS3A 341:345 mAb COS3A 337:345 mAb COS3A 337:345 From these, mAb COS3A was selected for biochemical and functional analysis. 27001651 7 75 theme cells 794:798 arg1 protein 766:772 COS3A-precipitated protein 747:772 COS3A-precipitated protein 747:772 N-glycosidase F treatment of COS3A-precipitated protein and culture of U937 cells in the presence of tunicamycin before cell lysate preparation were used to study the glycosylation state of proteins. 27001651 7 75 theme cells 794:798 arg1 culture 778:784 culture 778:784 culture of U937 cells in the presence of tunicamycin 778:829 N-glycosidase F treatment of COS3A-precipitated protein and culture of U937 cells in the presence of tunicamycin before cell lysate preparation were used to study the glycosylation state of proteins. 27001651 6 76 theme Biochemical 561:571 arg1 characterization 573:588 Biochemical characterization 561:588 Biochemical characterization of the molecular target of COS3A 561:621 Biochemical characterization of the molecular target of COS3A was approached by immunoprecipitation, Western blotting and amino acid sequencing using LC-MS. 27001651 4 77 theme mAb 457:459 arg1 COS3A 461:465 the mAb COS3A 453:465 the mAb COS3A 453:465 OBJECTIVE To analyze the properties and function of the mAb COS3A. 27001651 11 78 theme CD63 1314:1317 arg1 molecule 1319:1326 the CD63 molecule 1310:1326 the CD63 molecule 1310:1326 LC-MS data and immunoprecipitation indicated that mAb COS3A bound specifically to the CD63 molecule. 27001651 7 79 theme lysate 843:848 arg1 preparation 850:860 cell lysate preparation 838:860 cell lysate preparation 838:860 N-glycosidase F treatment of COS3A-precipitated protein and culture of U937 cells in the presence of tunicamycin before cell lysate preparation were used to study the glycosylation state of proteins. 27001651 1 80 theme Monoclonal 100:109 arg1 mAbs 123:126 mAbs 123:126 mAbs 123:126 BACKGROUND Monoclonal antibodies (mAbs) have become essential tools in life science research and in medicine, because of their extreme specificity. 27001651 1 80 theme Monoclonal 100:109 arg1 antibodies 111:120 BACKGROUND Monoclonal antibodies 89:120 BACKGROUND Monoclonal antibodies (mAbs) 89:127 BACKGROUND Monoclonal antibodies (mAbs) have become essential tools in life science research and in medicine, because of their extreme specificity. 27001651 0 81 theme COS3A 39:43 arg1 analysis 27:34 Biochemical and functional analysis 0:34 Biochemical and functional analysis of COS3A, a novel CD63-specific monoclonal antibody 0:86 Biochemical and functional analysis of COS3A, a novel CD63-specific monoclonal antibody. 27001651 14 82 theme therapeutic 1800:1810 arg1 approaches 1812:1821 therapeutic approaches 1800:1821 therapeutic approaches 1800:1821 MAb COS3A is, therefore, suitable for both biochemical and functional studies of CD63, and may be used for further study of the mechanism of phagocytosis and also in therapeutic approaches. 27001651 11 83 theme LC-MS 1228:1232 arg1 data 1234:1237 LC-MS data 1228:1237 LC-MS data 1228:1237 LC-MS data and immunoprecipitation indicated that mAb COS3A bound specifically to the CD63 molecule. 27001651 1 84 theme extreme 216:222 arg1 specificity 224:234 their extreme specificity 210:234 their extreme specificity 210:234 BACKGROUND Monoclonal antibodies (mAbs) have become essential tools in life science research and in medicine, because of their extreme specificity. 27001651 7 85 from treatment 734:742 arg1 presence 807:814 the presence 803:814 the presence of tunicamycin 803:829 N-glycosidase F treatment of COS3A-precipitated protein and culture of U937 cells in the presence of tunicamycin before cell lysate preparation were used to study the glycosylation state of proteins. 27001651 11 86 theme mAb 1278:1280 arg1 COS3A 1282:1286 mAb COS3A 1278:1286 mAb COS3A 1278:1286 LC-MS data and immunoprecipitation indicated that mAb COS3A bound specifically to the CD63 molecule. 27001651 14 87 theme phagocytosis 1775:1786 arg1 mechanism 1762:1770 the mechanism 1758:1770 the mechanism of phagocytosis 1758:1786 MAb COS3A is, therefore, suitable for both biochemical and functional studies of CD63, and may be used for further study of the mechanism of phagocytosis and also in therapeutic approaches. 27001651 13 88 theme diminished 1504:1513 arg1 granulocyte 1515:1525 strongly diminished granulocyte 1495:1525 strongly diminished granulocyte phagocytosis 1495:1538 CONCLUSIONS The mAb COS3A recognized the CD63 molecule and strongly diminished granulocyte phagocytosis of E. coli, suggesting that CD63 may play a crucial role in the initial step of phagocytosis. 27001651 14 89 theme mechanism 1762:1770 arg1 study 1749:1753 further study 1741:1753 further study of the mechanism of phagocytosis 1741:1786 MAb COS3A is, therefore, suitable for both biochemical and functional studies of CD63, and may be used for further study of the mechanism of phagocytosis and also in therapeutic approaches. 26206502 2 0 theme N-glycoproteins 370:384 arg1 deglycosylation 341:355 the deglycosylation 337:355 the deglycosylation of misfolded N-glycoproteins that are destined for proteasomal degradation or as the result of the degradation of dolichol-linked oligosaccharides (DLOs), which serve as glycan donor substrates in N-glycosylation reactions 337:578 It is generally assumed that such fOSs are produced by the deglycosylation of misfolded N-glycoproteins that are destined for proteasomal degradation or as the result of the degradation of dolichol-linked oligosaccharides (DLOs), which serve as glycan donor substrates in N-glycosylation reactions. 26206502 0 1 theme oligosaccharides 98:113 arg1 degradation 67:77 the degradation 63:77 the degradation of dolichol-linked oligosaccharides in mammalian cells 63:132 Cytosolic-free oligosaccharides are predominantly generated by the degradation of dolichol-linked oligosaccharides in mammalian cells. 26206502 5 2 theme Glc3Man9GlcNAc2-pyrophosphate-dolichol 1089:1126 arg1 degradation 1058:1068 the degradation 1054:1068 the degradation of fully assembled Glc3Man9GlcNAc2-pyrophosphate-dolichol (PP-Dol) in the lumen of the endoplasmic reticulum 1054:1177 Quantitative analyses of fOSs using digitonin-permeabilized cells revealed that they are generated by the degradation of fully assembled Glc3Man9GlcNAc2-pyrophosphate-dolichol (PP-Dol) in the lumen of the endoplasmic reticulum. 26206502 2 3 theme misfolded 360:368 arg1 N-glycoproteins 370:384 misfolded N-glycoproteins 360:384 misfolded N-glycoproteins that are destined for proteasomal degradation or as the result of the degradation of dolichol-linked oligosaccharides (DLOs), which serve as glycan donor substrates in N-glycosylation reactions 360:578 It is generally assumed that such fOSs are produced by the deglycosylation of misfolded N-glycoproteins that are destined for proteasomal degradation or as the result of the degradation of dolichol-linked oligosaccharides (DLOs), which serve as glycan donor substrates in N-glycosylation reactions. 26206502 2 3 theme misfolded 360:368 arg1 result 442:447 the result 438:447 the result of the degradation of dolichol-linked oligosaccharides (DLOs), which serve as glycan donor substrates in N-glycosylation reactions 438:578 It is generally assumed that such fOSs are produced by the deglycosylation of misfolded N-glycoproteins that are destined for proteasomal degradation or as the result of the degradation of dolichol-linked oligosaccharides (DLOs), which serve as glycan donor substrates in N-glycosylation reactions. 26206502 4 4 from ablation 790:797 arg1 fibroblasts 879:889 mouse embryonic fibroblasts 863:889 mouse embryonic fibroblasts 863:889 The ablation of the cytosolic deglycosylating enzymes, PNGase and ENGase, in mouse embryonic fibroblasts had little effect on the amount of cytosolic fOSs generated. 26206502 6 5 theme N-glycosylation 1273:1287 arg1 peptide 1298:1304 an N-glycosylation acceptor peptide 1270:1304 an N-glycosylation acceptor peptide that is recognized by the oligosaccharyltransferase (OST) 1270:1362 Because the degradation of Glc3Man9GlcNAc2-PP-Dol is greatly inhibited in the presence of an N-glycosylation acceptor peptide that is recognized by the oligosaccharyltransferase (OST), the OST-mediated hydrolysis of DLO is the most likely mechanism responsible for the production of a large fraction of the cytosolic fOSs. 26206502 4 6 contain had 891:893 arg2 effect 902:907 little effect 895:907 little effect 895:907 The ablation of the cytosolic deglycosylating enzymes, PNGase and ENGase, in mouse embryonic fibroblasts had little effect on the amount of cytosolic fOSs generated. 26206502 4 6 contain had 891:893 arg1 ablation 790:797 The ablation 786:797 The ablation of the cytosolic deglycosylating enzymes, PNGase and ENGase, in mouse embryonic fibroblasts 786:889 The ablation of the cytosolic deglycosylating enzymes, PNGase and ENGase, in mouse embryonic fibroblasts had little effect on the amount of cytosolic fOSs generated. 26206502 0 7 theme mammalian 118:126 arg1 cells 128:132 mammalian cells 118:132 mammalian cells 118:132 Cytosolic-free oligosaccharides are predominantly generated by the degradation of dolichol-linked oligosaccharides in mammalian cells. 26206502 0 8 from degradation 67:77 arg1 cells 128:132 mammalian cells 118:132 mammalian cells 118:132 Cytosolic-free oligosaccharides are predominantly generated by the degradation of dolichol-linked oligosaccharides in mammalian cells. 26206502 4 9 theme little 895:900 arg1 effect 902:907 little effect 895:907 little effect 895:907 The ablation of the cytosolic deglycosylating enzymes, PNGase and ENGase, in mouse embryonic fibroblasts had little effect on the amount of cytosolic fOSs generated. 26206502 5 10 theme digitonin-permeabilized 988:1010 arg1 cells 1012:1016 digitonin-permeabilized cells 988:1016 digitonin-permeabilized cells 988:1016 Quantitative analyses of fOSs using digitonin-permeabilized cells revealed that they are generated by the degradation of fully assembled Glc3Man9GlcNAc2-pyrophosphate-dolichol (PP-Dol) in the lumen of the endoplasmic reticulum. 26206502 2 11 theme glycan 527:532 arg1 oligosaccharides 487:502 dolichol-linked oligosaccharides 471:502 dolichol-linked oligosaccharides (DLOs) 471:509 It is generally assumed that such fOSs are produced by the deglycosylation of misfolded N-glycoproteins that are destined for proteasomal degradation or as the result of the degradation of dolichol-linked oligosaccharides (DLOs), which serve as glycan donor substrates in N-glycosylation reactions. 26206502 2 11 theme glycan 527:532 arg1 substrates 540:549 glycan donor substrates 527:549 glycan donor substrates in N-glycosylation reactions 527:578 It is generally assumed that such fOSs are produced by the deglycosylation of misfolded N-glycoproteins that are destined for proteasomal degradation or as the result of the degradation of dolichol-linked oligosaccharides (DLOs), which serve as glycan donor substrates in N-glycosylation reactions. 26206502 3 12 theme -independent 745:756 arg1 pathway 758:764 an endo-β-N-acetylglucosaminidase (ENGase)-independent pathway 703:764 an endo-β-N-acetylglucosaminidase (ENGase)-independent pathway in mammalian cells 703:783 The findings reported herein show that the majority of cytosolic fOSs are generated by a peptide:N-glycanase (PNGase) and an endo-β-N-acetylglucosaminidase (ENGase)-independent pathway in mammalian cells. 26206502 3 13 from pathway 758:764 arg1 cells 779:783 mammalian cells 769:783 mammalian cells 769:783 The findings reported herein show that the majority of cytosolic fOSs are generated by a peptide:N-glycanase (PNGase) and an endo-β-N-acetylglucosaminidase (ENGase)-independent pathway in mammalian cells. 26206502 1 14 theme eukaryotic 187:196 arg1 cells 198:202 eukaryotic cells 187:202 eukaryotic cells 187:202 During asparagine (N)-linked protein glycosylation, eukaryotic cells generate considerable amounts of free oligosaccharides (fOSs) in the cytosol. 26206502 6 15 theme likely 1412:1417 arg1 hydrolysis 1382:1391 the OST-mediated hydrolysis 1365:1391 the OST-mediated hydrolysis of DLO 1365:1398 Because the degradation of Glc3Man9GlcNAc2-PP-Dol is greatly inhibited in the presence of an N-glycosylation acceptor peptide that is recognized by the oligosaccharyltransferase (OST), the OST-mediated hydrolysis of DLO is the most likely mechanism responsible for the production of a large fraction of the cytosolic fOSs. 26206502 6 15 theme likely 1412:1417 arg1 mechanism 1419:1427 the most likely mechanism 1403:1427 the most likely mechanism responsible for the production of a large fraction of the cytosolic fOSs 1403:1500 Because the degradation of Glc3Man9GlcNAc2-PP-Dol is greatly inhibited in the presence of an N-glycosylation acceptor peptide that is recognized by the oligosaccharyltransferase (OST), the OST-mediated hydrolysis of DLO is the most likely mechanism responsible for the production of a large fraction of the cytosolic fOSs. 26206502 0 16 theme Cytosolic-free 0:13 arg1 oligosaccharides 15:30 Cytosolic-free oligosaccharides 0:30 Cytosolic-free oligosaccharides 0:30 Cytosolic-free oligosaccharides are predominantly generated by the degradation of dolichol-linked oligosaccharides in mammalian cells. 26206502 2 17 theme proteasomal 408:418 arg1 degradation 420:430 proteasomal degradation 408:430 proteasomal degradation 408:430 It is generally assumed that such fOSs are produced by the deglycosylation of misfolded N-glycoproteins that are destined for proteasomal degradation or as the result of the degradation of dolichol-linked oligosaccharides (DLOs), which serve as glycan donor substrates in N-glycosylation reactions. 26206502 5 18 theme endoplasmic 1157:1167 arg1 reticulum 1169:1177 the endoplasmic reticulum 1153:1177 the endoplasmic reticulum 1153:1177 Quantitative analyses of fOSs using digitonin-permeabilized cells revealed that they are generated by the degradation of fully assembled Glc3Man9GlcNAc2-pyrophosphate-dolichol (PP-Dol) in the lumen of the endoplasmic reticulum. 26206502 4 19 theme embryonic 869:877 arg1 fibroblasts 879:889 mouse embryonic fibroblasts 863:889 mouse embryonic fibroblasts 863:889 The ablation of the cytosolic deglycosylating enzymes, PNGase and ENGase, in mouse embryonic fibroblasts had little effect on the amount of cytosolic fOSs generated. 26206502 2 20 link dolichol-linked 471:485 arg1 oligosaccharides 487:502 dolichol-linked oligosaccharides 471:502 dolichol-linked oligosaccharides (DLOs) 471:509 It is generally assumed that such fOSs are produced by the deglycosylation of misfolded N-glycoproteins that are destined for proteasomal degradation or as the result of the degradation of dolichol-linked oligosaccharides (DLOs), which serve as glycan donor substrates in N-glycosylation reactions. 26206502 2 20 link dolichol-linked 471:485 arg1 substrates 540:549 glycan donor substrates 527:549 glycan donor substrates in N-glycosylation reactions 527:578 It is generally assumed that such fOSs are produced by the deglycosylation of misfolded N-glycoproteins that are destined for proteasomal degradation or as the result of the degradation of dolichol-linked oligosaccharides (DLOs), which serve as glycan donor substrates in N-glycosylation reactions. 26206502 2 20 link dolichol-linked 471:485 arg1 DLOs 505:508 DLOs 505:508 DLOs 505:508 It is generally assumed that such fOSs are produced by the deglycosylation of misfolded N-glycoproteins that are destined for proteasomal degradation or as the result of the degradation of dolichol-linked oligosaccharides (DLOs), which serve as glycan donor substrates in N-glycosylation reactions. 26206502 5 21 theme Quantitative 952:963 arg1 analyses 965:972 Quantitative analyses 952:972 Quantitative analyses of fOSs using digitonin-permeabilized cells 952:1016 Quantitative analyses of fOSs using digitonin-permeabilized cells revealed that they are generated by the degradation of fully assembled Glc3Man9GlcNAc2-pyrophosphate-dolichol (PP-Dol) in the lumen of the endoplasmic reticulum. 26206502 2 22 theme degradation 456:466 arg1 N-glycoproteins 370:384 misfolded N-glycoproteins 360:384 misfolded N-glycoproteins that are destined for proteasomal degradation or as the result of the degradation of dolichol-linked oligosaccharides (DLOs), which serve as glycan donor substrates in N-glycosylation reactions 360:578 It is generally assumed that such fOSs are produced by the deglycosylation of misfolded N-glycoproteins that are destined for proteasomal degradation or as the result of the degradation of dolichol-linked oligosaccharides (DLOs), which serve as glycan donor substrates in N-glycosylation reactions. 26206502 2 22 theme degradation 456:466 arg1 result 442:447 the result 438:447 the result of the degradation of dolichol-linked oligosaccharides (DLOs), which serve as glycan donor substrates in N-glycosylation reactions 438:578 It is generally assumed that such fOSs are produced by the deglycosylation of misfolded N-glycoproteins that are destined for proteasomal degradation or as the result of the degradation of dolichol-linked oligosaccharides (DLOs), which serve as glycan donor substrates in N-glycosylation reactions. 26206502 3 23 theme mammalian 769:777 arg1 cells 779:783 mammalian cells 769:783 mammalian cells 769:783 The findings reported herein show that the majority of cytosolic fOSs are generated by a peptide:N-glycanase (PNGase) and an endo-β-N-acetylglucosaminidase (ENGase)-independent pathway in mammalian cells. 26206502 4 24 theme mouse 863:867 arg1 fibroblasts 879:889 mouse embryonic fibroblasts 863:889 mouse embryonic fibroblasts 863:889 The ablation of the cytosolic deglycosylating enzymes, PNGase and ENGase, in mouse embryonic fibroblasts had little effect on the amount of cytosolic fOSs generated. 26206502 6 25 theme Glc3Man9GlcNAc2-PP-Dol 1207:1228 arg1 degradation 1192:1202 the degradation 1188:1202 the degradation of Glc3Man9GlcNAc2-PP-Dol 1188:1228 Because the degradation of Glc3Man9GlcNAc2-PP-Dol is greatly inhibited in the presence of an N-glycosylation acceptor peptide that is recognized by the oligosaccharyltransferase (OST), the OST-mediated hydrolysis of DLO is the most likely mechanism responsible for the production of a large fraction of the cytosolic fOSs. 26206502 5 26 from degradation 1058:1068 arg1 lumen 1144:1148 the lumen 1140:1148 the lumen of the endoplasmic reticulum 1140:1177 Quantitative analyses of fOSs using digitonin-permeabilized cells revealed that they are generated by the degradation of fully assembled Glc3Man9GlcNAc2-pyrophosphate-dolichol (PP-Dol) in the lumen of the endoplasmic reticulum. 26206502 1 27 theme considerable 213:224 arg1 fOSs 260:263 fOSs 260:263 fOSs 260:263 During asparagine (N)-linked protein glycosylation, eukaryotic cells generate considerable amounts of free oligosaccharides (fOSs) in the cytosol. 26206502 1 27 theme considerable 213:224 arg1 amounts 226:232 considerable amounts 213:232 considerable amounts of free oligosaccharides (fOSs) 213:264 During asparagine (N)-linked protein glycosylation, eukaryotic cells generate considerable amounts of free oligosaccharides (fOSs) in the cytosol. 26206502 1 27 theme considerable 213:224 arg1 oligosaccharides 242:257 free oligosaccharides 237:257 free oligosaccharides (fOSs) 237:264 During asparagine (N)-linked protein glycosylation, eukaryotic cells generate considerable amounts of free oligosaccharides (fOSs) in the cytosol. 26206502 2 28 theme N-glycosylation 554:568 arg1 reactions 570:578 N-glycosylation reactions 554:578 N-glycosylation reactions 554:578 It is generally assumed that such fOSs are produced by the deglycosylation of misfolded N-glycoproteins that are destined for proteasomal degradation or as the result of the degradation of dolichol-linked oligosaccharides (DLOs), which serve as glycan donor substrates in N-glycosylation reactions. 26206502 4 29 theme fOSs 936:939 arg1 amount 916:921 the amount 912:921 the amount of cytosolic fOSs generated 912:949 The ablation of the cytosolic deglycosylating enzymes, PNGase and ENGase, in mouse embryonic fibroblasts had little effect on the amount of cytosolic fOSs generated. 26206502 4 29 theme fOSs 936:939 arg1 fOSs 936:939 cytosolic fOSs 926:939 cytosolic fOSs generated 926:949 The ablation of the cytosolic deglycosylating enzymes, PNGase and ENGase, in mouse embryonic fibroblasts had little effect on the amount of cytosolic fOSs generated. 26206502 6 30 theme acceptor 1289:1296 arg1 peptide 1298:1304 an N-glycosylation acceptor peptide 1270:1304 an N-glycosylation acceptor peptide that is recognized by the oligosaccharyltransferase (OST) 1270:1362 Because the degradation of Glc3Man9GlcNAc2-PP-Dol is greatly inhibited in the presence of an N-glycosylation acceptor peptide that is recognized by the oligosaccharyltransferase (OST), the OST-mediated hydrolysis of DLO is the most likely mechanism responsible for the production of a large fraction of the cytosolic fOSs. 26206502 5 31 theme fOSs 977:980 arg1 analyses 965:972 Quantitative analyses 952:972 Quantitative analyses of fOSs using digitonin-permeabilized cells 952:1016 Quantitative analyses of fOSs using digitonin-permeabilized cells revealed that they are generated by the degradation of fully assembled Glc3Man9GlcNAc2-pyrophosphate-dolichol (PP-Dol) in the lumen of the endoplasmic reticulum. 26206502 6 32 theme cytosolic 1487:1495 arg1 fOSs 1497:1500 the cytosolic fOSs 1483:1500 the cytosolic fOSs 1483:1500 Because the degradation of Glc3Man9GlcNAc2-PP-Dol is greatly inhibited in the presence of an N-glycosylation acceptor peptide that is recognized by the oligosaccharyltransferase (OST), the OST-mediated hydrolysis of DLO is the most likely mechanism responsible for the production of a large fraction of the cytosolic fOSs. 26206502 4 33 theme cytosolic 926:934 arg1 fOSs 936:939 cytosolic fOSs 926:939 cytosolic fOSs generated 926:949 The ablation of the cytosolic deglycosylating enzymes, PNGase and ENGase, in mouse embryonic fibroblasts had little effect on the amount of cytosolic fOSs generated. 26206502 2 34 theme such 311:314 arg1 fOSs 316:319 such fOSs 311:319 such fOSs 311:319 It is generally assumed that such fOSs are produced by the deglycosylation of misfolded N-glycoproteins that are destined for proteasomal degradation or as the result of the degradation of dolichol-linked oligosaccharides (DLOs), which serve as glycan donor substrates in N-glycosylation reactions. 26206502 1 35 link -linked 156:162 arg1 glycosylation 172:184 asparagine (N)-linked protein glycosylation 142:184 asparagine (N)-linked protein glycosylation 142:184 During asparagine (N)-linked protein glycosylation, eukaryotic cells generate considerable amounts of free oligosaccharides (fOSs) in the cytosol. 26206502 1 36 theme free 237:240 arg1 fOSs 260:263 fOSs 260:263 fOSs 260:263 During asparagine (N)-linked protein glycosylation, eukaryotic cells generate considerable amounts of free oligosaccharides (fOSs) in the cytosol. 26206502 1 36 theme free 237:240 arg1 oligosaccharides 242:257 free oligosaccharides 237:257 free oligosaccharides (fOSs) 237:264 During asparagine (N)-linked protein glycosylation, eukaryotic cells generate considerable amounts of free oligosaccharides (fOSs) in the cytosol. 26206502 2 37 gly N-glycoproteins 370:384 arg1 N-glycoproteins 370:384 misfolded N-glycoproteins 360:384 misfolded N-glycoproteins that are destined for proteasomal degradation or as the result of the degradation of dolichol-linked oligosaccharides (DLOs), which serve as glycan donor substrates in N-glycosylation reactions 360:578 It is generally assumed that such fOSs are produced by the deglycosylation of misfolded N-glycoproteins that are destined for proteasomal degradation or as the result of the degradation of dolichol-linked oligosaccharides (DLOs), which serve as glycan donor substrates in N-glycosylation reactions. 26206502 2 37 gly N-glycoproteins 370:384 arg1 result 442:447 the result 438:447 the result of the degradation of dolichol-linked oligosaccharides (DLOs), which serve as glycan donor substrates in N-glycosylation reactions 438:578 It is generally assumed that such fOSs are produced by the deglycosylation of misfolded N-glycoproteins that are destined for proteasomal degradation or as the result of the degradation of dolichol-linked oligosaccharides (DLOs), which serve as glycan donor substrates in N-glycosylation reactions. 26206502 6 38 theme fOSs 1497:1500 arg1 fraction 1471:1478 a large fraction 1463:1478 a large fraction of the cytosolic fOSs 1463:1500 Because the degradation of Glc3Man9GlcNAc2-PP-Dol is greatly inhibited in the presence of an N-glycosylation acceptor peptide that is recognized by the oligosaccharyltransferase (OST), the OST-mediated hydrolysis of DLO is the most likely mechanism responsible for the production of a large fraction of the cytosolic fOSs. 26206502 1 39 theme oligosaccharides 242:257 arg1 fOSs 260:263 fOSs 260:263 fOSs 260:263 During asparagine (N)-linked protein glycosylation, eukaryotic cells generate considerable amounts of free oligosaccharides (fOSs) in the cytosol. 26206502 1 39 theme oligosaccharides 242:257 arg1 amounts 226:232 considerable amounts 213:232 considerable amounts of free oligosaccharides (fOSs) 213:264 During asparagine (N)-linked protein glycosylation, eukaryotic cells generate considerable amounts of free oligosaccharides (fOSs) in the cytosol. 26206502 1 39 theme oligosaccharides 242:257 arg1 oligosaccharides 242:257 free oligosaccharides 237:257 free oligosaccharides (fOSs) 237:264 During asparagine (N)-linked protein glycosylation, eukaryotic cells generate considerable amounts of free oligosaccharides (fOSs) in the cytosol. 26206502 2 40 theme oligosaccharides 487:502 arg1 degradation 456:466 the degradation 452:466 the degradation of dolichol-linked oligosaccharides (DLOs), which serve as glycan donor substrates in N-glycosylation reactions 452:578 It is generally assumed that such fOSs are produced by the deglycosylation of misfolded N-glycoproteins that are destined for proteasomal degradation or as the result of the degradation of dolichol-linked oligosaccharides (DLOs), which serve as glycan donor substrates in N-glycosylation reactions. 26206502 2 41 gly deglycosylation 341:355 arg1 N-glycoproteins 370:384 misfolded N-glycoproteins 360:384 misfolded N-glycoproteins that are destined for proteasomal degradation or as the result of the degradation of dolichol-linked oligosaccharides (DLOs), which serve as glycan donor substrates in N-glycosylation reactions 360:578 It is generally assumed that such fOSs are produced by the deglycosylation of misfolded N-glycoproteins that are destined for proteasomal degradation or as the result of the degradation of dolichol-linked oligosaccharides (DLOs), which serve as glycan donor substrates in N-glycosylation reactions. 26206502 2 41 gly deglycosylation 341:355 arg1 result 442:447 the result 438:447 the result of the degradation of dolichol-linked oligosaccharides (DLOs), which serve as glycan donor substrates in N-glycosylation reactions 438:578 It is generally assumed that such fOSs are produced by the deglycosylation of misfolded N-glycoproteins that are destined for proteasomal degradation or as the result of the degradation of dolichol-linked oligosaccharides (DLOs), which serve as glycan donor substrates in N-glycosylation reactions. 26206502 4 42 gly deglycosylating 816:830 arg0 enzymes 832:838 the cytosolic deglycosylating enzymes 802:838 the cytosolic deglycosylating enzymes 802:838 The ablation of the cytosolic deglycosylating enzymes, PNGase and ENGase, in mouse embryonic fibroblasts had little effect on the amount of cytosolic fOSs generated. 26206502 4 42 gly deglycosylating 816:830 arg0 PNGase 841:846 PNGase 841:846 PNGase 841:846 The ablation of the cytosolic deglycosylating enzymes, PNGase and ENGase, in mouse embryonic fibroblasts had little effect on the amount of cytosolic fOSs generated. 26206502 4 42 gly deglycosylating 816:830 arg0 ENGase 852:857 ENGase 852:857 ENGase 852:857 The ablation of the cytosolic deglycosylating enzymes, PNGase and ENGase, in mouse embryonic fibroblasts had little effect on the amount of cytosolic fOSs generated. 26206502 6 43 theme peptide 1298:1304 arg1 presence 1258:1265 the presence 1254:1265 the presence of an N-glycosylation acceptor peptide that is recognized by the oligosaccharyltransferase (OST) 1254:1362 Because the degradation of Glc3Man9GlcNAc2-PP-Dol is greatly inhibited in the presence of an N-glycosylation acceptor peptide that is recognized by the oligosaccharyltransferase (OST), the OST-mediated hydrolysis of DLO is the most likely mechanism responsible for the production of a large fraction of the cytosolic fOSs. 26206502 2 44 theme dolichol-linked 471:485 arg1 oligosaccharides 487:502 dolichol-linked oligosaccharides 471:502 dolichol-linked oligosaccharides (DLOs) 471:509 It is generally assumed that such fOSs are produced by the deglycosylation of misfolded N-glycoproteins that are destined for proteasomal degradation or as the result of the degradation of dolichol-linked oligosaccharides (DLOs), which serve as glycan donor substrates in N-glycosylation reactions. 26206502 2 44 theme dolichol-linked 471:485 arg1 substrates 540:549 glycan donor substrates 527:549 glycan donor substrates in N-glycosylation reactions 527:578 It is generally assumed that such fOSs are produced by the deglycosylation of misfolded N-glycoproteins that are destined for proteasomal degradation or as the result of the degradation of dolichol-linked oligosaccharides (DLOs), which serve as glycan donor substrates in N-glycosylation reactions. 26206502 2 44 theme dolichol-linked 471:485 arg1 DLOs 505:508 DLOs 505:508 DLOs 505:508 It is generally assumed that such fOSs are produced by the deglycosylation of misfolded N-glycoproteins that are destined for proteasomal degradation or as the result of the degradation of dolichol-linked oligosaccharides (DLOs), which serve as glycan donor substrates in N-glycosylation reactions. 26206502 6 45 theme fraction 1471:1478 arg1 production 1449:1458 the production 1445:1458 the production of a large fraction of the cytosolic fOSs 1445:1500 Because the degradation of Glc3Man9GlcNAc2-PP-Dol is greatly inhibited in the presence of an N-glycosylation acceptor peptide that is recognized by the oligosaccharyltransferase (OST), the OST-mediated hydrolysis of DLO is the most likely mechanism responsible for the production of a large fraction of the cytosolic fOSs. 26206502 5 46 theme assembled 1079:1087 arg1 Glc3Man9GlcNAc2-pyrophosphate-dolichol 1089:1126 fully assembled Glc3Man9GlcNAc2-pyrophosphate-dolichol 1073:1126 fully assembled Glc3Man9GlcNAc2-pyrophosphate-dolichol (PP-Dol) 1073:1135 Quantitative analyses of fOSs using digitonin-permeabilized cells revealed that they are generated by the degradation of fully assembled Glc3Man9GlcNAc2-pyrophosphate-dolichol (PP-Dol) in the lumen of the endoplasmic reticulum. 26206502 5 46 theme assembled 1079:1087 arg1 PP-Dol 1129:1134 PP-Dol 1129:1134 PP-Dol 1129:1134 Quantitative analyses of fOSs using digitonin-permeabilized cells revealed that they are generated by the degradation of fully assembled Glc3Man9GlcNAc2-pyrophosphate-dolichol (PP-Dol) in the lumen of the endoplasmic reticulum. 26206502 0 47 link dolichol-linked 82:96 arg1 oligosaccharides 98:113 dolichol-linked oligosaccharides 82:113 dolichol-linked oligosaccharides 82:113 Cytosolic-free oligosaccharides are predominantly generated by the degradation of dolichol-linked oligosaccharides in mammalian cells. 26206502 4 48 theme deglycosylating 816:830 arg1 PNGase 841:846 PNGase 841:846 PNGase 841:846 The ablation of the cytosolic deglycosylating enzymes, PNGase and ENGase, in mouse embryonic fibroblasts had little effect on the amount of cytosolic fOSs generated. 26206502 4 48 theme deglycosylating 816:830 arg1 enzymes 832:838 the cytosolic deglycosylating enzymes 802:838 the cytosolic deglycosylating enzymes 802:838 The ablation of the cytosolic deglycosylating enzymes, PNGase and ENGase, in mouse embryonic fibroblasts had little effect on the amount of cytosolic fOSs generated. 26206502 4 48 theme deglycosylating 816:830 arg1 ENGase 852:857 ENGase 852:857 ENGase 852:857 The ablation of the cytosolic deglycosylating enzymes, PNGase and ENGase, in mouse embryonic fibroblasts had little effect on the amount of cytosolic fOSs generated. 26206502 6 49 theme OST-mediated 1369:1380 arg1 hydrolysis 1382:1391 the OST-mediated hydrolysis 1365:1391 the OST-mediated hydrolysis of DLO 1365:1398 Because the degradation of Glc3Man9GlcNAc2-PP-Dol is greatly inhibited in the presence of an N-glycosylation acceptor peptide that is recognized by the oligosaccharyltransferase (OST), the OST-mediated hydrolysis of DLO is the most likely mechanism responsible for the production of a large fraction of the cytosolic fOSs. 26206502 6 49 theme OST-mediated 1369:1380 arg1 mechanism 1419:1427 the most likely mechanism 1403:1427 the most likely mechanism responsible for the production of a large fraction of the cytosolic fOSs 1403:1500 Because the degradation of Glc3Man9GlcNAc2-PP-Dol is greatly inhibited in the presence of an N-glycosylation acceptor peptide that is recognized by the oligosaccharyltransferase (OST), the OST-mediated hydrolysis of DLO is the most likely mechanism responsible for the production of a large fraction of the cytosolic fOSs. 26206502 4 50 theme cytosolic 806:814 arg1 PNGase 841:846 PNGase 841:846 PNGase 841:846 The ablation of the cytosolic deglycosylating enzymes, PNGase and ENGase, in mouse embryonic fibroblasts had little effect on the amount of cytosolic fOSs generated. 26206502 4 50 theme cytosolic 806:814 arg1 enzymes 832:838 the cytosolic deglycosylating enzymes 802:838 the cytosolic deglycosylating enzymes 802:838 The ablation of the cytosolic deglycosylating enzymes, PNGase and ENGase, in mouse embryonic fibroblasts had little effect on the amount of cytosolic fOSs generated. 26206502 4 50 theme cytosolic 806:814 arg1 ENGase 852:857 ENGase 852:857 ENGase 852:857 The ablation of the cytosolic deglycosylating enzymes, PNGase and ENGase, in mouse embryonic fibroblasts had little effect on the amount of cytosolic fOSs generated. 26206502 3 51 theme fOSs 646:649 arg1 majority 624:631 the majority 620:631 the majority of cytosolic fOSs 620:649 The findings reported herein show that the majority of cytosolic fOSs are generated by a peptide:N-glycanase (PNGase) and an endo-β-N-acetylglucosaminidase (ENGase)-independent pathway in mammalian cells. 26206502 6 52 theme DLO 1396:1398 arg1 hydrolysis 1382:1391 the OST-mediated hydrolysis 1365:1391 the OST-mediated hydrolysis of DLO 1365:1398 Because the degradation of Glc3Man9GlcNAc2-PP-Dol is greatly inhibited in the presence of an N-glycosylation acceptor peptide that is recognized by the oligosaccharyltransferase (OST), the OST-mediated hydrolysis of DLO is the most likely mechanism responsible for the production of a large fraction of the cytosolic fOSs. 26206502 6 52 theme DLO 1396:1398 arg1 mechanism 1419:1427 the most likely mechanism 1403:1427 the most likely mechanism responsible for the production of a large fraction of the cytosolic fOSs 1403:1500 Because the degradation of Glc3Man9GlcNAc2-PP-Dol is greatly inhibited in the presence of an N-glycosylation acceptor peptide that is recognized by the oligosaccharyltransferase (OST), the OST-mediated hydrolysis of DLO is the most likely mechanism responsible for the production of a large fraction of the cytosolic fOSs. 26206502 2 53 from substrates 540:549 arg1 reactions 570:578 N-glycosylation reactions 554:578 N-glycosylation reactions 554:578 It is generally assumed that such fOSs are produced by the deglycosylation of misfolded N-glycoproteins that are destined for proteasomal degradation or as the result of the degradation of dolichol-linked oligosaccharides (DLOs), which serve as glycan donor substrates in N-glycosylation reactions. 26206502 6 54 theme responsible 1429:1439 arg1 hydrolysis 1382:1391 the OST-mediated hydrolysis 1365:1391 the OST-mediated hydrolysis of DLO 1365:1398 Because the degradation of Glc3Man9GlcNAc2-PP-Dol is greatly inhibited in the presence of an N-glycosylation acceptor peptide that is recognized by the oligosaccharyltransferase (OST), the OST-mediated hydrolysis of DLO is the most likely mechanism responsible for the production of a large fraction of the cytosolic fOSs. 26206502 6 54 theme responsible 1429:1439 arg1 mechanism 1419:1427 the most likely mechanism 1403:1427 the most likely mechanism responsible for the production of a large fraction of the cytosolic fOSs 1403:1500 Because the degradation of Glc3Man9GlcNAc2-PP-Dol is greatly inhibited in the presence of an N-glycosylation acceptor peptide that is recognized by the oligosaccharyltransferase (OST), the OST-mediated hydrolysis of DLO is the most likely mechanism responsible for the production of a large fraction of the cytosolic fOSs. 26206502 0 55 theme dolichol-linked 82:96 arg1 oligosaccharides 98:113 dolichol-linked oligosaccharides 82:113 dolichol-linked oligosaccharides 82:113 Cytosolic-free oligosaccharides are predominantly generated by the degradation of dolichol-linked oligosaccharides in mammalian cells. 26206502 4 56 theme enzymes 832:838 arg1 ablation 790:797 The ablation 786:797 The ablation of the cytosolic deglycosylating enzymes, PNGase and ENGase, in mouse embryonic fibroblasts 786:889 The ablation of the cytosolic deglycosylating enzymes, PNGase and ENGase, in mouse embryonic fibroblasts had little effect on the amount of cytosolic fOSs generated. 26206502 1 57 theme -linked 156:162 arg1 glycosylation 172:184 asparagine (N)-linked protein glycosylation 142:184 asparagine (N)-linked protein glycosylation 142:184 During asparagine (N)-linked protein glycosylation, eukaryotic cells generate considerable amounts of free oligosaccharides (fOSs) in the cytosol. 26206502 3 58 from N-glycanase 678:688 arg1 cells 779:783 mammalian cells 769:783 mammalian cells 769:783 The findings reported herein show that the majority of cytosolic fOSs are generated by a peptide:N-glycanase (PNGase) and an endo-β-N-acetylglucosaminidase (ENGase)-independent pathway in mammalian cells. 26206502 5 59 theme reticulum 1169:1177 arg1 lumen 1144:1148 the lumen 1140:1148 the lumen of the endoplasmic reticulum 1140:1177 Quantitative analyses of fOSs using digitonin-permeabilized cells revealed that they are generated by the degradation of fully assembled Glc3Man9GlcNAc2-pyrophosphate-dolichol (PP-Dol) in the lumen of the endoplasmic reticulum. 26206502 3 60 theme cytosolic 636:644 arg1 fOSs 646:649 cytosolic fOSs 636:649 cytosolic fOSs 636:649 The findings reported herein show that the majority of cytosolic fOSs are generated by a peptide:N-glycanase (PNGase) and an endo-β-N-acetylglucosaminidase (ENGase)-independent pathway in mammalian cells. 26206502 6 61 theme large 1465:1469 arg1 fraction 1471:1478 a large fraction 1463:1478 a large fraction of the cytosolic fOSs 1463:1500 Because the degradation of Glc3Man9GlcNAc2-PP-Dol is greatly inhibited in the presence of an N-glycosylation acceptor peptide that is recognized by the oligosaccharyltransferase (OST), the OST-mediated hydrolysis of DLO is the most likely mechanism responsible for the production of a large fraction of the cytosolic fOSs. 26206502 1 62 theme protein 164:170 arg1 glycosylation 172:184 asparagine (N)-linked protein glycosylation 142:184 asparagine (N)-linked protein glycosylation 142:184 During asparagine (N)-linked protein glycosylation, eukaryotic cells generate considerable amounts of free oligosaccharides (fOSs) in the cytosol. 26206502 2 63 theme donor 534:538 arg1 oligosaccharides 487:502 dolichol-linked oligosaccharides 471:502 dolichol-linked oligosaccharides (DLOs) 471:509 It is generally assumed that such fOSs are produced by the deglycosylation of misfolded N-glycoproteins that are destined for proteasomal degradation or as the result of the degradation of dolichol-linked oligosaccharides (DLOs), which serve as glycan donor substrates in N-glycosylation reactions. 26206502 2 63 theme donor 534:538 arg1 substrates 540:549 glycan donor substrates 527:549 glycan donor substrates in N-glycosylation reactions 527:578 It is generally assumed that such fOSs are produced by the deglycosylation of misfolded N-glycoproteins that are destined for proteasomal degradation or as the result of the degradation of dolichol-linked oligosaccharides (DLOs), which serve as glycan donor substrates in N-glycosylation reactions. 26086806 5 0 theme definitive 959:968 arg1 design 980:985 a definitive screening design 957:985 a definitive screening design of experiments (DOE) 957:1006 Furthermore, to increase the depth of glycome coverage, we executed a definitive screening design of experiments (DOE) to optimize the MS parameters for glycan analyses. 26086806 1 1 theme High-throughput 171:185 arg1 processing 201:210 High-throughput, quantitative processing 171:210 High-throughput, quantitative processing of N-linked glycans 171:230 High-throughput, quantitative processing of N-linked glycans would facilitate large-scale studies correlating the glycome with disease and open the field to basic and applied researchers. 26086806 1 2 link N-linked 215:222 arg1 glycans 224:230 N-linked glycans 215:230 N-linked glycans 215:230 High-throughput, quantitative processing of N-linked glycans would facilitate large-scale studies correlating the glycome with disease and open the field to basic and applied researchers. 26086806 6 3 from increase 1205:1212 arg1 abundances 1221:1230 ion abundances 1217:1230 ion abundances 1217:1230 We optimized MS parameters across five N-glycan responses using a standard glycan mixture, translated these to plasma and achieved up to a 3-fold increase in ion abundances. 26086806 0 4 theme Filter 101:106 arg1 Comparison 87:96 Sensitive Comparison 77:96 Sensitive Comparison of Filter and Solid Phase Extraction 77:133 Definitive Screening Design Optimization of Mass Spectrometry Parameters for Sensitive Comparison of Filter and Solid Phase Extraction Purified, INLIGHT Plasma N-Glycans. 26086806 5 5 theme experiments 990:1000 arg1 design 980:985 a definitive screening design 957:985 a definitive screening design of experiments (DOE) 957:1006 Furthermore, to increase the depth of glycome coverage, we executed a definitive screening design of experiments (DOE) to optimize the MS parameters for glycan analyses. 26086806 4 6 from terms 793:797 arg1 different 771:779 different 771:779 different 771:779 We demonstrate that FANGS-INLIGHT purification was not significantly different from SPE in terms of glycan abundances, variability, functional classes, or molecular weight distributions. 26086806 2 7 dep meet 372:375 arg1 FANGS 435:439 FANGS 435:439 FANGS 435:439 We sought to meet these goals by coupling filter-aided-N-glycan separation (FANGS) to the individuality normalization when labeling with glycan hydrazide tags (INLIGHT) for analysis of plasma. 26086806 0 8 theme Phase 118:122 arg1 Extraction 124:133 Solid Phase Extraction 112:133 Solid Phase Extraction 112:133 Definitive Screening Design Optimization of Mass Spectrometry Parameters for Sensitive Comparison of Filter and Solid Phase Extraction Purified, INLIGHT Plasma N-Glycans. 26086806 4 9 theme weight 867:872 arg1 distributions 874:886 molecular weight distributions 857:886 molecular weight distributions 857:886 We demonstrate that FANGS-INLIGHT purification was not significantly different from SPE in terms of glycan abundances, variability, functional classes, or molecular weight distributions. 26086806 4 10 theme glycan 802:807 arg1 abundances 809:818 glycan abundances 802:818 glycan abundances 802:818 We demonstrate that FANGS-INLIGHT purification was not significantly different from SPE in terms of glycan abundances, variability, functional classes, or molecular weight distributions. 26086806 0 11 theme Solid 112:116 arg1 Extraction 124:133 Solid Phase Extraction 112:133 Solid Phase Extraction 112:133 Definitive Screening Design Optimization of Mass Spectrometry Parameters for Sensitive Comparison of Filter and Solid Phase Extraction Purified, INLIGHT Plasma N-Glycans. 26086806 5 12 theme glycome 927:933 arg1 coverage 935:942 glycome coverage 927:942 glycome coverage 927:942 Furthermore, to increase the depth of glycome coverage, we executed a definitive screening design of experiments (DOE) to optimize the MS parameters for glycan analyses. 26086806 4 13 theme molecular 857:865 arg1 distributions 874:886 molecular weight distributions 857:886 molecular weight distributions 857:886 We demonstrate that FANGS-INLIGHT purification was not significantly different from SPE in terms of glycan abundances, variability, functional classes, or molecular weight distributions. 26086806 4 14 from SPE 786:788 arg1 different 771:779 different 771:779 different 771:779 We demonstrate that FANGS-INLIGHT purification was not significantly different from SPE in terms of glycan abundances, variability, functional classes, or molecular weight distributions. 26086806 3 15 theme quantitative 554:565 arg1 comparison 567:576 A quantitative comparison 552:576 A quantitative comparison of this method 552:591 A quantitative comparison of this method was conducted against solid phase extraction (SPE), a ubiquitous and trusted method for glycan purification. 26086806 6 16 theme N-glycan 1098:1105 arg1 responses 1107:1115 five N-glycan responses 1093:1115 five N-glycan responses using a standard glycan mixture 1093:1147 We optimized MS parameters across five N-glycan responses using a standard glycan mixture, translated these to plasma and achieved up to a 3-fold increase in ion abundances. 26086806 0 17 theme Screening 11:19 arg1 Optimization 28:39 Definitive Screening Design Optimization 0:39 Definitive Screening Design Optimization 0:39 Definitive Screening Design Optimization of Mass Spectrometry Parameters for Sensitive Comparison of Filter and Solid Phase Extraction Purified, INLIGHT Plasma N-Glycans. 26086806 2 18 theme filter-aided-N-glycan 401:421 arg1 separation 423:432 coupling filter-aided-N-glycan separation 392:432 coupling filter-aided-N-glycan separation 392:432 We sought to meet these goals by coupling filter-aided-N-glycan separation (FANGS) to the individuality normalization when labeling with glycan hydrazide tags (INLIGHT) for analysis of plasma. 26086806 0 19 theme Definitive 0:9 arg1 Optimization 28:39 Definitive Screening Design Optimization 0:39 Definitive Screening Design Optimization 0:39 Definitive Screening Design Optimization of Mass Spectrometry Parameters for Sensitive Comparison of Filter and Solid Phase Extraction Purified, INLIGHT Plasma N-Glycans. 26086806 4 20 theme distributions 874:886 arg1 terms 793:797 terms 793:797 terms of glycan abundances, variability, functional classes, or molecular weight distributions 793:886 We demonstrate that FANGS-INLIGHT purification was not significantly different from SPE in terms of glycan abundances, variability, functional classes, or molecular weight distributions. 26086806 4 21 from different 771:779 arg1 terms 793:797 terms 793:797 terms of glycan abundances, variability, functional classes, or molecular weight distributions 793:886 We demonstrate that FANGS-INLIGHT purification was not significantly different from SPE in terms of glycan abundances, variability, functional classes, or molecular weight distributions. 26086806 1 22 dep High-throughput 171:185 arg1 quantitative 188:199 quantitative 188:199 quantitative 188:199 High-throughput, quantitative processing of N-linked glycans would facilitate large-scale studies correlating the glycome with disease and open the field to basic and applied researchers. 26086806 2 23 theme coupling 392:399 arg1 separation 423:432 coupling filter-aided-N-glycan separation 392:432 coupling filter-aided-N-glycan separation 392:432 We sought to meet these goals by coupling filter-aided-N-glycan separation (FANGS) to the individuality normalization when labeling with glycan hydrazide tags (INLIGHT) for analysis of plasma. 26086806 5 24 theme glycan 1042:1047 arg1 analyses 1049:1056 glycan analyses 1042:1056 glycan analyses 1042:1056 Furthermore, to increase the depth of glycome coverage, we executed a definitive screening design of experiments (DOE) to optimize the MS parameters for glycan analyses. 26086806 5 25 theme screening 970:978 arg1 design 980:985 a definitive screening design 957:985 a definitive screening design of experiments (DOE) 957:1006 Furthermore, to increase the depth of glycome coverage, we executed a definitive screening design of experiments (DOE) to optimize the MS parameters for glycan analyses. 26086806 4 26 theme classes 845:851 arg1 terms 793:797 terms 793:797 terms of glycan abundances, variability, functional classes, or molecular weight distributions 793:886 We demonstrate that FANGS-INLIGHT purification was not significantly different from SPE in terms of glycan abundances, variability, functional classes, or molecular weight distributions. 26086806 1 27 theme N-linked 215:222 arg1 glycans 224:230 N-linked glycans 215:230 N-linked glycans 215:230 High-throughput, quantitative processing of N-linked glycans would facilitate large-scale studies correlating the glycome with disease and open the field to basic and applied researchers. 26086806 0 28 theme Design 21:26 arg1 Optimization 28:39 Definitive Screening Design Optimization 0:39 Definitive Screening Design Optimization 0:39 Definitive Screening Design Optimization of Mass Spectrometry Parameters for Sensitive Comparison of Filter and Solid Phase Extraction Purified, INLIGHT Plasma N-Glycans. 26086806 0 29 theme Extraction 124:133 arg1 Comparison 87:96 Sensitive Comparison 77:96 Sensitive Comparison of Filter and Solid Phase Extraction 77:133 Definitive Screening Design Optimization of Mass Spectrometry Parameters for Sensitive Comparison of Filter and Solid Phase Extraction Purified, INLIGHT Plasma N-Glycans. 26086806 3 30 theme method 586:591 arg1 comparison 567:576 A quantitative comparison 552:576 A quantitative comparison of this method 552:591 A quantitative comparison of this method was conducted against solid phase extraction (SPE), a ubiquitous and trusted method for glycan purification. 26086806 1 31 theme glycans 224:230 arg1 processing 201:210 High-throughput, quantitative processing 171:210 High-throughput, quantitative processing of N-linked glycans 171:230 High-throughput, quantitative processing of N-linked glycans would facilitate large-scale studies correlating the glycome with disease and open the field to basic and applied researchers. 26086806 0 32 theme Mass 44:47 arg1 Spectrometry 49:60 Mass Spectrometry 44:60 Mass Spectrometry Parameters for Sensitive Comparison of Filter and Solid Phase Extraction 44:133 Definitive Screening Design Optimization of Mass Spectrometry Parameters for Sensitive Comparison of Filter and Solid Phase Extraction Purified, INLIGHT Plasma N-Glycans. 26086806 3 33 theme trusted 662:668 arg1 extraction 627:636 solid phase extraction 615:636 solid phase extraction (SPE) 615:642 A quantitative comparison of this method was conducted against solid phase extraction (SPE), a ubiquitous and trusted method for glycan purification. 26086806 3 33 theme trusted 662:668 arg1 method 670:675 a ubiquitous and trusted method 645:675 a ubiquitous and trusted method for glycan purification 645:699 A quantitative comparison of this method was conducted against solid phase extraction (SPE), a ubiquitous and trusted method for glycan purification. 26086806 3 34 theme phase 621:625 arg1 SPE 639:641 SPE 639:641 SPE 639:641 A quantitative comparison of this method was conducted against solid phase extraction (SPE), a ubiquitous and trusted method for glycan purification. 26086806 3 34 theme phase 621:625 arg1 extraction 627:636 solid phase extraction 615:636 solid phase extraction (SPE) 615:642 A quantitative comparison of this method was conducted against solid phase extraction (SPE), a ubiquitous and trusted method for glycan purification. 26086806 3 34 theme phase 621:625 arg1 method 670:675 a ubiquitous and trusted method 645:675 a ubiquitous and trusted method for glycan purification 645:699 A quantitative comparison of this method was conducted against solid phase extraction (SPE), a ubiquitous and trusted method for glycan purification. 26086806 6 35 theme MS 1072:1073 arg1 parameters 1075:1084 MS parameters 1072:1084 MS parameters 1072:1084 We optimized MS parameters across five N-glycan responses using a standard glycan mixture, translated these to plasma and achieved up to a 3-fold increase in ion abundances. 26086806 2 36 theme hydrazide 503:511 arg1 INLIGHT 519:525 INLIGHT 519:525 INLIGHT 519:525 We sought to meet these goals by coupling filter-aided-N-glycan separation (FANGS) to the individuality normalization when labeling with glycan hydrazide tags (INLIGHT) for analysis of plasma. 26086806 2 36 theme hydrazide 503:511 arg1 tags 513:516 glycan hydrazide tags 496:516 glycan hydrazide tags (INLIGHT) for analysis of plasma 496:549 We sought to meet these goals by coupling filter-aided-N-glycan separation (FANGS) to the individuality normalization when labeling with glycan hydrazide tags (INLIGHT) for analysis of plasma. 26086806 1 37 theme basic 328:332 arg1 researchers 346:356 basic and applied researchers 328:356 basic and applied researchers 328:356 High-throughput, quantitative processing of N-linked glycans would facilitate large-scale studies correlating the glycome with disease and open the field to basic and applied researchers. 26086806 4 38 theme functional 834:843 arg1 classes 845:851 functional classes 834:851 functional classes 834:851 We demonstrate that FANGS-INLIGHT purification was not significantly different from SPE in terms of glycan abundances, variability, functional classes, or molecular weight distributions. 26086806 5 39 theme MS 1024:1025 arg1 parameters 1027:1036 the MS parameters 1020:1036 the MS parameters for glycan analyses 1020:1056 Furthermore, to increase the depth of glycome coverage, we executed a definitive screening design of experiments (DOE) to optimize the MS parameters for glycan analyses. 26086806 0 40 theme Parameters 62:71 arg1 Optimization 28:39 Definitive Screening Design Optimization 0:39 Definitive Screening Design Optimization 0:39 Definitive Screening Design Optimization of Mass Spectrometry Parameters for Sensitive Comparison of Filter and Solid Phase Extraction Purified, INLIGHT Plasma N-Glycans. 26086806 3 41 theme ubiquitous 647:656 arg1 extraction 627:636 solid phase extraction 615:636 solid phase extraction (SPE) 615:642 A quantitative comparison of this method was conducted against solid phase extraction (SPE), a ubiquitous and trusted method for glycan purification. 26086806 3 41 theme ubiquitous 647:656 arg1 method 670:675 a ubiquitous and trusted method 645:675 a ubiquitous and trusted method for glycan purification 645:699 A quantitative comparison of this method was conducted against solid phase extraction (SPE), a ubiquitous and trusted method for glycan purification. 26086806 5 42 theme coverage 935:942 arg1 depth 918:922 the depth 914:922 the depth of glycome coverage 914:942 Furthermore, to increase the depth of glycome coverage, we executed a definitive screening design of experiments (DOE) to optimize the MS parameters for glycan analyses. 26086806 0 43 theme Spectrometry 49:60 arg1 Parameters 62:71 Mass Spectrometry Parameters 44:71 Mass Spectrometry Parameters for Sensitive Comparison of Filter and Solid Phase Extraction 44:133 Definitive Screening Design Optimization of Mass Spectrometry Parameters for Sensitive Comparison of Filter and Solid Phase Extraction Purified, INLIGHT Plasma N-Glycans. 26086806 1 44 theme applied 338:344 arg1 researchers 346:356 basic and applied researchers 328:356 basic and applied researchers 328:356 High-throughput, quantitative processing of N-linked glycans would facilitate large-scale studies correlating the glycome with disease and open the field to basic and applied researchers. 26086806 0 45 theme Plasma 153:158 arg1 N-Glycans 160:168 Plasma N-Glycans 153:168 Plasma N-Glycans 153:168 Definitive Screening Design Optimization of Mass Spectrometry Parameters for Sensitive Comparison of Filter and Solid Phase Extraction Purified, INLIGHT Plasma N-Glycans. 26086806 3 46 theme glycan 681:686 arg1 purification 688:699 glycan purification 681:699 glycan purification 681:699 A quantitative comparison of this method was conducted against solid phase extraction (SPE), a ubiquitous and trusted method for glycan purification. 26086806 3 47 theme solid 615:619 arg1 SPE 639:641 SPE 639:641 SPE 639:641 A quantitative comparison of this method was conducted against solid phase extraction (SPE), a ubiquitous and trusted method for glycan purification. 26086806 3 47 theme solid 615:619 arg1 extraction 627:636 solid phase extraction 615:636 solid phase extraction (SPE) 615:642 A quantitative comparison of this method was conducted against solid phase extraction (SPE), a ubiquitous and trusted method for glycan purification. 26086806 3 47 theme solid 615:619 arg1 method 670:675 a ubiquitous and trusted method 645:675 a ubiquitous and trusted method for glycan purification 645:699 A quantitative comparison of this method was conducted against solid phase extraction (SPE), a ubiquitous and trusted method for glycan purification. 26086806 4 48 theme FANGS-INLIGHT 722:734 arg1 purification 736:747 FANGS-INLIGHT purification 722:747 FANGS-INLIGHT purification 722:747 We demonstrate that FANGS-INLIGHT purification was not significantly different from SPE in terms of glycan abundances, variability, functional classes, or molecular weight distributions. 26086806 6 49 theme ion 1217:1219 arg1 abundances 1221:1230 ion abundances 1217:1230 ion abundances 1217:1230 We optimized MS parameters across five N-glycan responses using a standard glycan mixture, translated these to plasma and achieved up to a 3-fold increase in ion abundances. 26086806 4 50 theme variability 821:831 arg1 terms 793:797 terms 793:797 terms of glycan abundances, variability, functional classes, or molecular weight distributions 793:886 We demonstrate that FANGS-INLIGHT purification was not significantly different from SPE in terms of glycan abundances, variability, functional classes, or molecular weight distributions. 26086806 6 51 theme glycan 1134:1139 arg1 mixture 1141:1147 a standard glycan mixture 1123:1147 a standard glycan mixture 1123:1147 We optimized MS parameters across five N-glycan responses using a standard glycan mixture, translated these to plasma and achieved up to a 3-fold increase in ion abundances. 26086806 1 52 theme large-scale 249:259 arg1 studies 261:267 large-scale studies 249:267 large-scale studies correlating the glycome with disease 249:304 High-throughput, quantitative processing of N-linked glycans would facilitate large-scale studies correlating the glycome with disease and open the field to basic and applied researchers. 26086806 4 53 theme abundances 809:818 arg1 terms 793:797 terms 793:797 terms of glycan abundances, variability, functional classes, or molecular weight distributions 793:886 We demonstrate that FANGS-INLIGHT purification was not significantly different from SPE in terms of glycan abundances, variability, functional classes, or molecular weight distributions. 26086806 6 54 theme standard 1125:1132 arg1 mixture 1141:1147 a standard glycan mixture 1123:1147 a standard glycan mixture 1123:1147 We optimized MS parameters across five N-glycan responses using a standard glycan mixture, translated these to plasma and achieved up to a 3-fold increase in ion abundances. 26086806 0 55 theme Sensitive 77:85 arg1 Comparison 87:96 Sensitive Comparison 77:96 Sensitive Comparison of Filter and Solid Phase Extraction 77:133 Definitive Screening Design Optimization of Mass Spectrometry Parameters for Sensitive Comparison of Filter and Solid Phase Extraction Purified, INLIGHT Plasma N-Glycans. 26086806 6 56 theme 3-fold 1198:1203 arg1 increase 1205:1212 a 3-fold increase 1196:1212 a 3-fold increase in ion abundances 1196:1230 We optimized MS parameters across five N-glycan responses using a standard glycan mixture, translated these to plasma and achieved up to a 3-fold increase in ion abundances. 26086806 2 57 theme glycan 496:501 arg1 INLIGHT 519:525 INLIGHT 519:525 INLIGHT 519:525 We sought to meet these goals by coupling filter-aided-N-glycan separation (FANGS) to the individuality normalization when labeling with glycan hydrazide tags (INLIGHT) for analysis of plasma. 26086806 2 57 theme glycan 496:501 arg1 tags 513:516 glycan hydrazide tags 496:516 glycan hydrazide tags (INLIGHT) for analysis of plasma 496:549 We sought to meet these goals by coupling filter-aided-N-glycan separation (FANGS) to the individuality normalization when labeling with glycan hydrazide tags (INLIGHT) for analysis of plasma. 26086806 2 58 theme individuality 449:461 arg1 normalization 463:475 the individuality normalization 445:475 the individuality normalization 445:475 We sought to meet these goals by coupling filter-aided-N-glycan separation (FANGS) to the individuality normalization when labeling with glycan hydrazide tags (INLIGHT) for analysis of plasma. 26086806 2 59 theme plasma 544:549 arg1 analysis 532:539 analysis 532:539 analysis of plasma 532:549 We sought to meet these goals by coupling filter-aided-N-glycan separation (FANGS) to the individuality normalization when labeling with glycan hydrazide tags (INLIGHT) for analysis of plasma. 25665441 3 0 theme Pulse-chase 700:710 arg1 labeling 712:719 Pulse-chase labeling 700:719 Pulse-chase labeling 700:719 Pulse-chase labeling and good knowledge on organelle-specific modifications of lysosomal proteins may enhance the information that can be obtained from such experiments. 25665441 2 1 theme protein 600:606 arg1 fraction 575:582 a very minor fraction 562:582 a very minor fraction of the cellular protein 562:606 A prerequisite in application of these techniques to lysosomal enzymes is the availability of an avid and specific antibody, because lysosomal proteins represent a very minor fraction of the cellular protein and must be purified without a significant loss many 1000-fold as conveniently as possible. 25665441 1 2 theme acids 159:163 arg1 precursors 139:148 radioactive precursors 127:148 radioactive precursors of amino acids and/or modifier groups 127:186 Incorporation of radioactive precursors of amino acids and/or modifier groups into proteins, isolation and sizing of polypeptide species of interest, and finally their detection and characterization provide a robust handle to examine the life cycle and varied modifications of any protein. 25665441 1 3 theme interest 250:257 arg1 species 239:245 polypeptide species 227:245 polypeptide species of interest 227:257 Incorporation of radioactive precursors of amino acids and/or modifier groups into proteins, isolation and sizing of polypeptide species of interest, and finally their detection and characterization provide a robust handle to examine the life cycle and varied modifications of any protein. 25665441 0 4 theme pulse-chase 63:73 arg1 labeling 75:82 pulse-chase labeling 63:82 pulse-chase labeling 63:82 Biosynthesis, targeting, and processing of lysosomal proteins: pulse-chase labeling and immune precipitation. 25665441 8 5 theme Z 1678:1678 arg1 deglycosylation 1627:1641 deglycosylation 1627:1641 deglycosylation of metabolically labeled cathepsin Z 1627:1678 In addition, results on deglycosylation of metabolically labeled cathepsin Z are shown and the alterations in the apparent size of the glycopeptides are explained. 25665441 2 6 theme cellular 591:598 arg1 protein 600:606 the cellular protein 587:606 the cellular protein 587:606 A prerequisite in application of these techniques to lysosomal enzymes is the availability of an avid and specific antibody, because lysosomal proteins represent a very minor fraction of the cellular protein and must be purified without a significant loss many 1000-fold as conveniently as possible. 25665441 8 7 gly glycopeptides 1738:1750 arg2 glycopeptides 1738:1750 the glycopeptides 1734:1750 the glycopeptides 1734:1750 In addition, results on deglycosylation of metabolically labeled cathepsin Z are shown and the alterations in the apparent size of the glycopeptides are explained. 25665441 3 8 theme such 852:855 arg1 experiments 857:867 such experiments 852:867 such experiments 852:867 Pulse-chase labeling and good knowledge on organelle-specific modifications of lysosomal proteins may enhance the information that can be obtained from such experiments. 25665441 0 9 theme immune 88:93 arg1 precipitation 95:107 immune precipitation 88:107 immune precipitation 88:107 Biosynthesis, targeting, and processing of lysosomal proteins: pulse-chase labeling and immune precipitation. 25665441 1 10 theme life 348:351 arg1 cycle 353:357 the life cycle 344:357 the life cycle 344:357 Incorporation of radioactive precursors of amino acids and/or modifier groups into proteins, isolation and sizing of polypeptide species of interest, and finally their detection and characterization provide a robust handle to examine the life cycle and varied modifications of any protein. 25665441 4 11 theme labeling 909:916 arg1 experiments 918:928 pulse-chase labeling experiments 897:928 pulse-chase labeling experiments that have proven to work with a commercially available antibody against a mouse and a human lysosomal protease 897:1039 We describe procedures for pulse-chase labeling experiments that have proven to work with a commercially available antibody against a mouse and a human lysosomal protease and can be used as a reference in establishing the technique in any laboratory that has an access to a certified isotope facility and the knowledge to handle radioactivity safely. 25665441 2 12 theme significant 639:649 arg1 loss 651:654 a significant loss 637:654 a significant loss many 1000-fold 637:669 A prerequisite in application of these techniques to lysosomal enzymes is the availability of an avid and specific antibody, because lysosomal proteins represent a very minor fraction of the cellular protein and must be purified without a significant loss many 1000-fold as conveniently as possible. 25665441 8 13 from alterations 1698:1708 arg1 size 1726:1729 the apparent size 1713:1729 the apparent size of the glycopeptides 1713:1750 In addition, results on deglycosylation of metabolically labeled cathepsin Z are shown and the alterations in the apparent size of the glycopeptides are explained. 25665441 8 14 theme apparent 1717:1724 arg1 size 1726:1729 the apparent size 1713:1729 the apparent size of the glycopeptides 1713:1750 In addition, results on deglycosylation of metabolically labeled cathepsin Z are shown and the alterations in the apparent size of the glycopeptides are explained. 25665441 2 15 theme antibody 515:522 arg1 prerequisite 402:413 A prerequisite 400:413 A prerequisite in application of these techniques to lysosomal enzymes 400:469 A prerequisite in application of these techniques to lysosomal enzymes is the availability of an avid and specific antibody, because lysosomal proteins represent a very minor fraction of the cellular protein and must be purified without a significant loss many 1000-fold as conveniently as possible. 25665441 2 15 theme antibody 515:522 arg1 availability 478:489 the availability 474:489 the availability of an avid and specific antibody 474:522 A prerequisite in application of these techniques to lysosomal enzymes is the availability of an avid and specific antibody, because lysosomal proteins represent a very minor fraction of the cellular protein and must be purified without a significant loss many 1000-fold as conveniently as possible. 25665441 3 16 theme good 725:728 arg1 knowledge 730:738 good knowledge 725:738 good knowledge 725:738 Pulse-chase labeling and good knowledge on organelle-specific modifications of lysosomal proteins may enhance the information that can be obtained from such experiments. 25665441 4 17 theme pulse-chase 897:907 arg1 experiments 918:928 pulse-chase labeling experiments 897:928 pulse-chase labeling experiments that have proven to work with a commercially available antibody against a mouse and a human lysosomal protease 897:1039 We describe procedures for pulse-chase labeling experiments that have proven to work with a commercially available antibody against a mouse and a human lysosomal protease and can be used as a reference in establishing the technique in any laboratory that has an access to a certified isotope facility and the knowledge to handle radioactivity safely. 25665441 6 18 link N-linked 1398:1405 arg1 oligosaccharides 1407:1422 two N-linked oligosaccharides 1394:1422 two N-linked oligosaccharides 1394:1422 The present model protein cathepsin Z is synthesized as a larger proenzyme that contains two N-linked oligosaccharides and matures to a shorter single chain enzyme retaining the processed oligosaccharides. 25665441 3 19 theme lysosomal 779:787 arg1 proteins 789:796 lysosomal proteins 779:796 lysosomal proteins 779:796 Pulse-chase labeling and good knowledge on organelle-specific modifications of lysosomal proteins may enhance the information that can be obtained from such experiments. 25665441 2 20 theme specific 506:513 arg1 antibody 515:522 an avid and specific antibody 494:522 an avid and specific antibody 494:522 A prerequisite in application of these techniques to lysosomal enzymes is the availability of an avid and specific antibody, because lysosomal proteins represent a very minor fraction of the cellular protein and must be purified without a significant loss many 1000-fold as conveniently as possible. 25665441 8 21 from results 1616:1622 arg1 deglycosylation 1627:1641 deglycosylation 1627:1641 deglycosylation of metabolically labeled cathepsin Z 1627:1678 In addition, results on deglycosylation of metabolically labeled cathepsin Z are shown and the alterations in the apparent size of the glycopeptides are explained. 25665441 1 22 theme modifier 172:179 arg1 groups 181:186 modifier groups 172:186 modifier groups 172:186 Incorporation of radioactive precursors of amino acids and/or modifier groups into proteins, isolation and sizing of polypeptide species of interest, and finally their detection and characterization provide a robust handle to examine the life cycle and varied modifications of any protein. 25665441 7 23 theme mature 1590:1595 arg1 form 1597:1600 the mature form 1586:1600 the mature form 1586:1600 A pulse-chase experiment demonstrates the conversion of the precursor into the mature form. 25665441 1 24 theme varied 363:368 arg1 modifications 370:382 varied modifications 363:382 varied modifications 363:382 Incorporation of radioactive precursors of amino acids and/or modifier groups into proteins, isolation and sizing of polypeptide species of interest, and finally their detection and characterization provide a robust handle to examine the life cycle and varied modifications of any protein. 25665441 8 25 theme cathepsin 1668:1676 arg1 Z 1678:1678 metabolically labeled cathepsin Z 1646:1678 metabolically labeled cathepsin Z 1646:1678 In addition, results on deglycosylation of metabolically labeled cathepsin Z are shown and the alterations in the apparent size of the glycopeptides are explained. 25665441 5 26 theme crucial 1236:1242 arg1 steps 1244:1248 the crucial steps 1232:1248 the crucial steps 1232:1248 We discuss the crucial steps and refer to alternatives described in the literature. 25665441 4 27 theme certified 1144:1152 arg1 facility 1162:1169 a certified isotope facility 1142:1169 a certified isotope facility 1142:1169 We describe procedures for pulse-chase labeling experiments that have proven to work with a commercially available antibody against a mouse and a human lysosomal protease and can be used as a reference in establishing the technique in any laboratory that has an access to a certified isotope facility and the knowledge to handle radioactivity safely. 25665441 1 28 theme groups 181:186 arg1 precursors 139:148 radioactive precursors 127:148 radioactive precursors of amino acids and/or modifier groups 127:186 Incorporation of radioactive precursors of amino acids and/or modifier groups into proteins, isolation and sizing of polypeptide species of interest, and finally their detection and characterization provide a robust handle to examine the life cycle and varied modifications of any protein. 25665441 3 29 from labeling 712:719 arg1 modifications 762:774 organelle-specific modifications 743:774 organelle-specific modifications of lysosomal proteins 743:796 Pulse-chase labeling and good knowledge on organelle-specific modifications of lysosomal proteins may enhance the information that can be obtained from such experiments. 25665441 6 30 theme N-linked 1398:1405 arg1 oligosaccharides 1407:1422 two N-linked oligosaccharides 1394:1422 two N-linked oligosaccharides 1394:1422 The present model protein cathepsin Z is synthesized as a larger proenzyme that contains two N-linked oligosaccharides and matures to a shorter single chain enzyme retaining the processed oligosaccharides. 25665441 6 31 theme model 1317:1321 arg1 Z 1341:1341 The present model protein cathepsin Z 1305:1341 The present model protein cathepsin Z 1305:1341 The present model protein cathepsin Z is synthesized as a larger proenzyme that contains two N-linked oligosaccharides and matures to a shorter single chain enzyme retaining the processed oligosaccharides. 25665441 6 31 theme model 1317:1321 arg1 proenzyme 1370:1378 a larger proenzyme 1361:1378 a larger proenzyme that contains two N-linked oligosaccharides and matures to a shorter single chain enzyme retaining the processed oligosaccharides 1361:1508 The present model protein cathepsin Z is synthesized as a larger proenzyme that contains two N-linked oligosaccharides and matures to a shorter single chain enzyme retaining the processed oligosaccharides. 25665441 2 32 theme techniques 439:448 arg1 application 418:428 application 418:428 application of these techniques to lysosomal enzymes 418:469 A prerequisite in application of these techniques to lysosomal enzymes is the availability of an avid and specific antibody, because lysosomal proteins represent a very minor fraction of the cellular protein and must be purified without a significant loss many 1000-fold as conveniently as possible. 25665441 2 33 theme 1000-fold 661:669 arg1 loss 651:654 a significant loss 637:654 a significant loss many 1000-fold 637:669 A prerequisite in application of these techniques to lysosomal enzymes is the availability of an avid and specific antibody, because lysosomal proteins represent a very minor fraction of the cellular protein and must be purified without a significant loss many 1000-fold as conveniently as possible. 25665441 6 34 theme shorter 1441:1447 arg1 chain 1456:1460 shorter single chain 1441:1460 a shorter single chain enzyme retaining the processed oligosaccharides 1439:1508 The present model protein cathepsin Z is synthesized as a larger proenzyme that contains two N-linked oligosaccharides and matures to a shorter single chain enzyme retaining the processed oligosaccharides. 25665441 4 35 contain has 1125:1127 arg1 laboratory 1109:1118 any laboratory 1105:1118 any laboratory that has an access to a certified isotope facility and the knowledge to handle radioactivity safely 1105:1218 We describe procedures for pulse-chase labeling experiments that have proven to work with a commercially available antibody against a mouse and a human lysosomal protease and can be used as a reference in establishing the technique in any laboratory that has an access to a certified isotope facility and the knowledge to handle radioactivity safely. 25665441 4 35 contain has 1125:1127 arg2 access 1132:1137 an access 1129:1137 an access to a certified isotope facility and the knowledge to handle radioactivity safely 1129:1218 We describe procedures for pulse-chase labeling experiments that have proven to work with a commercially available antibody against a mouse and a human lysosomal protease and can be used as a reference in establishing the technique in any laboratory that has an access to a certified isotope facility and the knowledge to handle radioactivity safely. 25665441 3 36 from knowledge 730:738 arg1 modifications 762:774 organelle-specific modifications 743:774 organelle-specific modifications of lysosomal proteins 743:796 Pulse-chase labeling and good knowledge on organelle-specific modifications of lysosomal proteins may enhance the information that can be obtained from such experiments. 25665441 7 37 theme pulse-chase 1513:1523 arg1 experiment 1525:1534 A pulse-chase experiment 1511:1534 A pulse-chase experiment 1511:1534 A pulse-chase experiment demonstrates the conversion of the precursor into the mature form. 25665441 7 38 theme precursor 1571:1579 arg1 conversion 1553:1562 the conversion 1549:1562 the conversion of the precursor into the mature form 1549:1600 A pulse-chase experiment demonstrates the conversion of the precursor into the mature form. 25665441 4 39 theme lysosomal 1022:1030 arg1 protease 1032:1039 a human lysosomal protease 1014:1039 a human lysosomal protease 1014:1039 We describe procedures for pulse-chase labeling experiments that have proven to work with a commercially available antibody against a mouse and a human lysosomal protease and can be used as a reference in establishing the technique in any laboratory that has an access to a certified isotope facility and the knowledge to handle radioactivity safely. 25665441 3 40 theme organelle-specific 743:760 arg1 modifications 762:774 organelle-specific modifications 743:774 organelle-specific modifications of lysosomal proteins 743:796 Pulse-chase labeling and good knowledge on organelle-specific modifications of lysosomal proteins may enhance the information that can be obtained from such experiments. 25665441 2 41 theme lysosomal 533:541 arg1 proteins 543:550 lysosomal proteins 533:550 lysosomal proteins 533:550 A prerequisite in application of these techniques to lysosomal enzymes is the availability of an avid and specific antibody, because lysosomal proteins represent a very minor fraction of the cellular protein and must be purified without a significant loss many 1000-fold as conveniently as possible. 25665441 6 42 theme chain 1456:1460 arg1 enzyme 1462:1467 a shorter single chain enzyme 1439:1467 a shorter single chain enzyme retaining the processed oligosaccharides 1439:1508 The present model protein cathepsin Z is synthesized as a larger proenzyme that contains two N-linked oligosaccharides and matures to a shorter single chain enzyme retaining the processed oligosaccharides. 25665441 4 43 theme human 1016:1020 arg1 protease 1032:1039 a human lysosomal protease 1014:1039 a human lysosomal protease 1014:1039 We describe procedures for pulse-chase labeling experiments that have proven to work with a commercially available antibody against a mouse and a human lysosomal protease and can be used as a reference in establishing the technique in any laboratory that has an access to a certified isotope facility and the knowledge to handle radioactivity safely. 25665441 6 44 theme cathepsin 1331:1339 arg1 Z 1341:1341 The present model protein cathepsin Z 1305:1341 The present model protein cathepsin Z 1305:1341 The present model protein cathepsin Z is synthesized as a larger proenzyme that contains two N-linked oligosaccharides and matures to a shorter single chain enzyme retaining the processed oligosaccharides. 25665441 6 44 theme cathepsin 1331:1339 arg1 proenzyme 1370:1378 a larger proenzyme 1361:1378 a larger proenzyme that contains two N-linked oligosaccharides and matures to a shorter single chain enzyme retaining the processed oligosaccharides 1361:1508 The present model protein cathepsin Z is synthesized as a larger proenzyme that contains two N-linked oligosaccharides and matures to a shorter single chain enzyme retaining the processed oligosaccharides. 25665441 1 45 theme protein 391:397 arg1 cycle 353:357 the life cycle 344:357 the life cycle 344:357 Incorporation of radioactive precursors of amino acids and/or modifier groups into proteins, isolation and sizing of polypeptide species of interest, and finally their detection and characterization provide a robust handle to examine the life cycle and varied modifications of any protein. 25665441 1 45 theme protein 391:397 arg1 modifications 370:382 varied modifications 363:382 varied modifications 363:382 Incorporation of radioactive precursors of amino acids and/or modifier groups into proteins, isolation and sizing of polypeptide species of interest, and finally their detection and characterization provide a robust handle to examine the life cycle and varied modifications of any protein. 25665441 8 46 gly deglycosylation 1627:1641 arg1 Z 1678:1678 metabolically labeled cathepsin Z 1646:1678 metabolically labeled cathepsin Z 1646:1678 In addition, results on deglycosylation of metabolically labeled cathepsin Z are shown and the alterations in the apparent size of the glycopeptides are explained. 25665441 0 47 theme lysosomal 43:51 arg1 proteins 53:60 lysosomal proteins 43:60 lysosomal proteins 43:60 Biosynthesis, targeting, and processing of lysosomal proteins: pulse-chase labeling and immune precipitation. 25665441 4 48 theme available 975:983 arg1 antibody 985:992 a commercially available antibody 960:992 a commercially available antibody against a mouse 960:1008 We describe procedures for pulse-chase labeling experiments that have proven to work with a commercially available antibody against a mouse and a human lysosomal protease and can be used as a reference in establishing the technique in any laboratory that has an access to a certified isotope facility and the knowledge to handle radioactivity safely. 25665441 6 49 theme protein 1323:1329 arg1 Z 1341:1341 The present model protein cathepsin Z 1305:1341 The present model protein cathepsin Z 1305:1341 The present model protein cathepsin Z is synthesized as a larger proenzyme that contains two N-linked oligosaccharides and matures to a shorter single chain enzyme retaining the processed oligosaccharides. 25665441 6 49 theme protein 1323:1329 arg1 proenzyme 1370:1378 a larger proenzyme 1361:1378 a larger proenzyme that contains two N-linked oligosaccharides and matures to a shorter single chain enzyme retaining the processed oligosaccharides 1361:1508 The present model protein cathepsin Z is synthesized as a larger proenzyme that contains two N-linked oligosaccharides and matures to a shorter single chain enzyme retaining the processed oligosaccharides. 25665441 6 50 theme single 1449:1454 arg1 chain 1456:1460 shorter single chain 1441:1460 a shorter single chain enzyme retaining the processed oligosaccharides 1439:1508 The present model protein cathepsin Z is synthesized as a larger proenzyme that contains two N-linked oligosaccharides and matures to a shorter single chain enzyme retaining the processed oligosaccharides. 25665441 2 51 theme lysosomal 453:461 arg1 enzymes 463:469 lysosomal enzymes 453:469 lysosomal enzymes 453:469 A prerequisite in application of these techniques to lysosomal enzymes is the availability of an avid and specific antibody, because lysosomal proteins represent a very minor fraction of the cellular protein and must be purified without a significant loss many 1000-fold as conveniently as possible. 25665441 1 52 theme robust 319:324 arg1 handle 326:331 a robust handle 317:331 a robust handle to examine the life cycle and varied modifications of any protein 317:397 Incorporation of radioactive precursors of amino acids and/or modifier groups into proteins, isolation and sizing of polypeptide species of interest, and finally their detection and characterization provide a robust handle to examine the life cycle and varied modifications of any protein. 25665441 2 53 theme minor 569:573 arg1 fraction 575:582 a very minor fraction 562:582 a very minor fraction of the cellular protein 562:606 A prerequisite in application of these techniques to lysosomal enzymes is the availability of an avid and specific antibody, because lysosomal proteins represent a very minor fraction of the cellular protein and must be purified without a significant loss many 1000-fold as conveniently as possible. 25665441 8 54 theme glycopeptides 1738:1750 arg1 size 1726:1729 the apparent size 1713:1729 the apparent size of the glycopeptides 1713:1750 In addition, results on deglycosylation of metabolically labeled cathepsin Z are shown and the alterations in the apparent size of the glycopeptides are explained. 25665441 8 55 theme labeled 1660:1666 arg1 Z 1678:1678 metabolically labeled cathepsin Z 1646:1678 metabolically labeled cathepsin Z 1646:1678 In addition, results on deglycosylation of metabolically labeled cathepsin Z are shown and the alterations in the apparent size of the glycopeptides are explained. 25665441 3 56 theme proteins 789:796 arg1 modifications 762:774 organelle-specific modifications 743:774 organelle-specific modifications of lysosomal proteins 743:796 Pulse-chase labeling and good knowledge on organelle-specific modifications of lysosomal proteins may enhance the information that can be obtained from such experiments. 25665441 6 57 theme present 1309:1315 arg1 Z 1341:1341 The present model protein cathepsin Z 1305:1341 The present model protein cathepsin Z 1305:1341 The present model protein cathepsin Z is synthesized as a larger proenzyme that contains two N-linked oligosaccharides and matures to a shorter single chain enzyme retaining the processed oligosaccharides. 25665441 6 57 theme present 1309:1315 arg1 proenzyme 1370:1378 a larger proenzyme 1361:1378 a larger proenzyme that contains two N-linked oligosaccharides and matures to a shorter single chain enzyme retaining the processed oligosaccharides 1361:1508 The present model protein cathepsin Z is synthesized as a larger proenzyme that contains two N-linked oligosaccharides and matures to a shorter single chain enzyme retaining the processed oligosaccharides. 25665441 6 58 contain contains 1385:1392 arg2 oligosaccharides 1407:1422 two N-linked oligosaccharides 1394:1422 two N-linked oligosaccharides 1394:1422 The present model protein cathepsin Z is synthesized as a larger proenzyme that contains two N-linked oligosaccharides and matures to a shorter single chain enzyme retaining the processed oligosaccharides. 25665441 6 58 contain contains 1385:1392 arg1 proenzyme 1370:1378 a larger proenzyme 1361:1378 a larger proenzyme that contains two N-linked oligosaccharides and matures to a shorter single chain enzyme retaining the processed oligosaccharides 1361:1508 The present model protein cathepsin Z is synthesized as a larger proenzyme that contains two N-linked oligosaccharides and matures to a shorter single chain enzyme retaining the processed oligosaccharides. 25665441 6 58 contain contains 1385:1392 arg1 Z 1341:1341 The present model protein cathepsin Z 1305:1341 The present model protein cathepsin Z 1305:1341 The present model protein cathepsin Z is synthesized as a larger proenzyme that contains two N-linked oligosaccharides and matures to a shorter single chain enzyme retaining the processed oligosaccharides. 25665441 1 59 theme radioactive 127:137 arg1 precursors 139:148 radioactive precursors 127:148 radioactive precursors of amino acids and/or modifier groups 127:186 Incorporation of radioactive precursors of amino acids and/or modifier groups into proteins, isolation and sizing of polypeptide species of interest, and finally their detection and characterization provide a robust handle to examine the life cycle and varied modifications of any protein. 25665441 2 60 from prerequisite 402:413 arg1 application 418:428 application 418:428 application of these techniques to lysosomal enzymes 418:469 A prerequisite in application of these techniques to lysosomal enzymes is the availability of an avid and specific antibody, because lysosomal proteins represent a very minor fraction of the cellular protein and must be purified without a significant loss many 1000-fold as conveniently as possible. 25665441 1 61 theme precursors 139:148 arg1 isolation 203:211 isolation 203:211 isolation 203:211 Incorporation of radioactive precursors of amino acids and/or modifier groups into proteins, isolation and sizing of polypeptide species of interest, and finally their detection and characterization provide a robust handle to examine the life cycle and varied modifications of any protein. 25665441 1 61 theme precursors 139:148 arg1 Incorporation 110:122 Incorporation 110:122 Incorporation of radioactive precursors of amino acids and/or modifier groups into proteins 110:200 Incorporation of radioactive precursors of amino acids and/or modifier groups into proteins, isolation and sizing of polypeptide species of interest, and finally their detection and characterization provide a robust handle to examine the life cycle and varied modifications of any protein. 25665441 1 61 theme precursors 139:148 arg1 characterization 292:307 characterization 292:307 characterization 292:307 Incorporation of radioactive precursors of amino acids and/or modifier groups into proteins, isolation and sizing of polypeptide species of interest, and finally their detection and characterization provide a robust handle to examine the life cycle and varied modifications of any protein. 25665441 1 61 theme precursors 139:148 arg1 detection 278:286 detection 278:286 detection 278:286 Incorporation of radioactive precursors of amino acids and/or modifier groups into proteins, isolation and sizing of polypeptide species of interest, and finally their detection and characterization provide a robust handle to examine the life cycle and varied modifications of any protein. 25665441 1 61 theme precursors 139:148 arg1 sizing 217:222 sizing 217:222 sizing 217:222 Incorporation of radioactive precursors of amino acids and/or modifier groups into proteins, isolation and sizing of polypeptide species of interest, and finally their detection and characterization provide a robust handle to examine the life cycle and varied modifications of any protein. 25665441 1 62 theme polypeptide 227:237 arg1 species 239:245 polypeptide species 227:245 polypeptide species of interest 227:257 Incorporation of radioactive precursors of amino acids and/or modifier groups into proteins, isolation and sizing of polypeptide species of interest, and finally their detection and characterization provide a robust handle to examine the life cycle and varied modifications of any protein. 25665441 2 63 theme avid 497:500 arg1 antibody 515:522 an avid and specific antibody 494:522 an avid and specific antibody 494:522 A prerequisite in application of these techniques to lysosomal enzymes is the availability of an avid and specific antibody, because lysosomal proteins represent a very minor fraction of the cellular protein and must be purified without a significant loss many 1000-fold as conveniently as possible. 25665441 4 64 theme isotope 1154:1160 arg1 facility 1162:1169 a certified isotope facility 1142:1169 a certified isotope facility 1142:1169 We describe procedures for pulse-chase labeling experiments that have proven to work with a commercially available antibody against a mouse and a human lysosomal protease and can be used as a reference in establishing the technique in any laboratory that has an access to a certified isotope facility and the knowledge to handle radioactivity safely. 25665441 1 65 theme species 239:245 arg1 isolation 203:211 isolation 203:211 isolation 203:211 Incorporation of radioactive precursors of amino acids and/or modifier groups into proteins, isolation and sizing of polypeptide species of interest, and finally their detection and characterization provide a robust handle to examine the life cycle and varied modifications of any protein. 25665441 1 65 theme species 239:245 arg1 Incorporation 110:122 Incorporation 110:122 Incorporation of radioactive precursors of amino acids and/or modifier groups into proteins 110:200 Incorporation of radioactive precursors of amino acids and/or modifier groups into proteins, isolation and sizing of polypeptide species of interest, and finally their detection and characterization provide a robust handle to examine the life cycle and varied modifications of any protein. 25665441 1 65 theme species 239:245 arg1 characterization 292:307 characterization 292:307 characterization 292:307 Incorporation of radioactive precursors of amino acids and/or modifier groups into proteins, isolation and sizing of polypeptide species of interest, and finally their detection and characterization provide a robust handle to examine the life cycle and varied modifications of any protein. 25665441 1 65 theme species 239:245 arg1 detection 278:286 detection 278:286 detection 278:286 Incorporation of radioactive precursors of amino acids and/or modifier groups into proteins, isolation and sizing of polypeptide species of interest, and finally their detection and characterization provide a robust handle to examine the life cycle and varied modifications of any protein. 25665441 1 65 theme species 239:245 arg1 sizing 217:222 sizing 217:222 sizing 217:222 Incorporation of radioactive precursors of amino acids and/or modifier groups into proteins, isolation and sizing of polypeptide species of interest, and finally their detection and characterization provide a robust handle to examine the life cycle and varied modifications of any protein. 25665441 0 66 theme proteins 53:60 arg1 targeting 14:22 targeting 14:22 targeting 14:22 Biosynthesis, targeting, and processing of lysosomal proteins: pulse-chase labeling and immune precipitation. 25665441 0 66 theme proteins 53:60 arg1 processing 29:38 processing 29:38 processing 29:38 Biosynthesis, targeting, and processing of lysosomal proteins: pulse-chase labeling and immune precipitation. 25665441 0 66 theme proteins 53:60 arg1 Biosynthesis 0:11 Biosynthesis 0:11 Biosynthesis 0:11 Biosynthesis, targeting, and processing of lysosomal proteins: pulse-chase labeling and immune precipitation. 25665441 4 67 used used 1052:1055 arg2 reference 1062:1070 a reference 1060:1070 a reference in establishing the technique in any laboratory that has an access to a certified isotope facility and the knowledge to handle radioactivity safely 1060:1218 We describe procedures for pulse-chase labeling experiments that have proven to work with a commercially available antibody against a mouse and a human lysosomal protease and can be used as a reference in establishing the technique in any laboratory that has an access to a certified isotope facility and the knowledge to handle radioactivity safely. 25665441 4 67 used used 1052:1055 arg2 We 870:871 We 870:871 We 870:871 We describe procedures for pulse-chase labeling experiments that have proven to work with a commercially available antibody against a mouse and a human lysosomal protease and can be used as a reference in establishing the technique in any laboratory that has an access to a certified isotope facility and the knowledge to handle radioactivity safely. 25665441 0 68 dep Biosynthesis 0:11 arg1 labeling 75:82 pulse-chase labeling 63:82 pulse-chase labeling 63:82 Biosynthesis, targeting, and processing of lysosomal proteins: pulse-chase labeling and immune precipitation. 25665441 0 68 dep Biosynthesis 0:11 arg1 precipitation 95:107 immune precipitation 88:107 immune precipitation 88:107 Biosynthesis, targeting, and processing of lysosomal proteins: pulse-chase labeling and immune precipitation. 25665441 1 69 theme amino 153:157 arg1 acids 159:163 amino acids 153:163 amino acids 153:163 Incorporation of radioactive precursors of amino acids and/or modifier groups into proteins, isolation and sizing of polypeptide species of interest, and finally their detection and characterization provide a robust handle to examine the life cycle and varied modifications of any protein. 25665441 6 70 theme processed 1483:1491 arg1 oligosaccharides 1493:1508 the processed oligosaccharides 1479:1508 the processed oligosaccharides 1479:1508 The present model protein cathepsin Z is synthesized as a larger proenzyme that contains two N-linked oligosaccharides and matures to a shorter single chain enzyme retaining the processed oligosaccharides. 25665441 6 71 theme larger 1363:1368 arg1 Z 1341:1341 The present model protein cathepsin Z 1305:1341 The present model protein cathepsin Z 1305:1341 The present model protein cathepsin Z is synthesized as a larger proenzyme that contains two N-linked oligosaccharides and matures to a shorter single chain enzyme retaining the processed oligosaccharides. 25665441 6 71 theme larger 1363:1368 arg1 proenzyme 1370:1378 a larger proenzyme 1361:1378 a larger proenzyme that contains two N-linked oligosaccharides and matures to a shorter single chain enzyme retaining the processed oligosaccharides 1361:1508 The present model protein cathepsin Z is synthesized as a larger proenzyme that contains two N-linked oligosaccharides and matures to a shorter single chain enzyme retaining the processed oligosaccharides. 25655076 3 0 theme misfolded 710:718 arg1 regions 720:726 misfolded regions 710:726 misfolded regions of aberrant proteins 710:747 It has previously been demonstrated that EDEM1 and EDEM2 binding does not require the trimming of substrate glycans or even ERAD substrate glycosylation, thus suggesting that both chaperones probably recognize misfolded regions of aberrant proteins. 25655076 4 1 theme protein 865:871 arg1 determinants 873:884 protein determinants 865:884 protein determinants 865:884 RESULTS In this work, we focused on the substrate recognition by EDEM1 and EDEM2, asking whether hydrophobicity of protein determinants might be important for these interactions in human cells. 25655076 1 2 theme crucial 146:152 arg1 EDEM1 126:130 BACKGROUND EDEM1 115:130 BACKGROUND EDEM1 115:130 BACKGROUND EDEM1 and EDEM2 are crucial regulators of the endoplasmic reticulum (ER)-associated degradation (ERAD) that extracts misfolded glycoproteins from the calnexin chaperone system. 25655076 1 2 theme crucial 146:152 arg1 EDEM2 136:140 EDEM2 136:140 EDEM2 136:140 BACKGROUND EDEM1 and EDEM2 are crucial regulators of the endoplasmic reticulum (ER)-associated degradation (ERAD) that extracts misfolded glycoproteins from the calnexin chaperone system. 25655076 1 2 theme crucial 146:152 arg1 regulators 154:163 crucial regulators 146:163 crucial regulators of the endoplasmic reticulum (ER)-associated degradation (ERAD) that extracts misfolded glycoproteins from the calnexin chaperone system 146:300 BACKGROUND EDEM1 and EDEM2 are crucial regulators of the endoplasmic reticulum (ER)-associated degradation (ERAD) that extracts misfolded glycoproteins from the calnexin chaperone system. 25655076 5 3 theme misfolded 1085:1093 arg1 isoform 1119:1125 the pancreatic isoform 1104:1125 the pancreatic isoform of human β-secretase, BACE457 1104:1155 In the study we used ricin, a protein toxin that utilizes the ERAD pathway in its retrotranslocation from the ER to the cytosol, and a model misfolded protein, the pancreatic isoform of human β-secretase, BACE457. 25655076 5 3 theme misfolded 1085:1093 arg1 protein 1095:1101 a model misfolded protein 1077:1101 a model misfolded protein 1077:1101 In the study we used ricin, a protein toxin that utilizes the ERAD pathway in its retrotranslocation from the ER to the cytosol, and a model misfolded protein, the pancreatic isoform of human β-secretase, BACE457. 25655076 8 4 theme EDEM 1489:1492 arg1 proteins 1494:1501 EDEM proteins 1489:1501 EDEM proteins 1489:1501 Moreover, EDEM proteins can bind hydrophobic transmembrane regions of misfolded ERAD substrates. 25655076 2 5 theme mannose 347:353 arg1 trimming 355:362 mannose trimming 347:362 mannose trimming of N-linked glycans 347:382 The degradation of ERAD substrates involves mannose trimming of N-linked glycans; however the precise mechanism of substrate recognition and sorting to the ERAD pathway is still poorly understood. 25655076 9 6 theme regulation 1634:1643 arg1 understanding 1613:1625 the general understanding 1601:1625 the general understanding of the regulation of ERAD in mammalian cells 1601:1670 These data contribute to the general understanding of the regulation of ERAD in mammalian cells. 25655076 5 7 theme protein 974:980 arg1 toxin 982:986 a protein toxin 972:986 a protein toxin that utilizes the ERAD pathway in its retrotranslocation from the ER to the cytosol 972:1070 In the study we used ricin, a protein toxin that utilizes the ERAD pathway in its retrotranslocation from the ER to the cytosol, and a model misfolded protein, the pancreatic isoform of human β-secretase, BACE457. 25655076 6 8 theme mutated 1234:1240 arg1 forms 1242:1246 mutated forms 1234:1246 mutated forms with increased and decreased hydrophobicity 1234:1290 Mutations in the hydrophobic regions of these proteins allowed us to obtain mutated forms with increased and decreased hydrophobicity. 25655076 1 9 theme misfolded 243:251 arg1 glycoproteins 253:265 misfolded glycoproteins 243:265 misfolded glycoproteins 243:265 BACKGROUND EDEM1 and EDEM2 are crucial regulators of the endoplasmic reticulum (ER)-associated degradation (ERAD) that extracts misfolded glycoproteins from the calnexin chaperone system. 25655076 3 10 theme aberrant 731:738 arg1 proteins 740:747 aberrant proteins 731:747 aberrant proteins 731:747 It has previously been demonstrated that EDEM1 and EDEM2 binding does not require the trimming of substrate glycans or even ERAD substrate glycosylation, thus suggesting that both chaperones probably recognize misfolded regions of aberrant proteins. 25655076 4 11 theme determinants 873:884 arg1 hydrophobicity 847:860 hydrophobicity 847:860 hydrophobicity of protein determinants 847:884 RESULTS In this work, we focused on the substrate recognition by EDEM1 and EDEM2, asking whether hydrophobicity of protein determinants might be important for these interactions in human cells. 25655076 7 12 theme protein 1457:1463 arg1 determinants 1465:1476 protein determinants 1457:1476 protein determinants 1457:1476 CONCLUSIONS Our data provide the first evidence that recognition of ERAD substrates by EDEM1 and EDEM2 might be determined by a sufficiently high hydrophobicity of protein determinants. 25655076 9 13 from understanding 1613:1625 arg1 cells 1666:1670 mammalian cells 1656:1670 mammalian cells 1656:1670 These data contribute to the general understanding of the regulation of ERAD in mammalian cells. 25655076 3 14 theme proteins 740:747 arg1 regions 720:726 misfolded regions 710:726 misfolded regions of aberrant proteins 710:747 It has previously been demonstrated that EDEM1 and EDEM2 binding does not require the trimming of substrate glycans or even ERAD substrate glycosylation, thus suggesting that both chaperones probably recognize misfolded regions of aberrant proteins. 25655076 9 15 theme mammalian 1656:1664 arg1 cells 1666:1670 mammalian cells 1656:1670 mammalian cells 1656:1670 These data contribute to the general understanding of the regulation of ERAD in mammalian cells. 25655076 3 16 dep trimming 586:593 arg1 glycosylation 639:651 glycosylation 639:651 glycosylation 639:651 It has previously been demonstrated that EDEM1 and EDEM2 binding does not require the trimming of substrate glycans or even ERAD substrate glycosylation, thus suggesting that both chaperones probably recognize misfolded regions of aberrant proteins. 25655076 0 17 theme human 102:106 arg1 cells 108:112 human cells 102:112 human cells 102:112 Hydrophobicity of protein determinants influences the recognition of substrates by EDEM1 and EDEM2 in human cells. 25655076 2 18 link N-linked 367:374 arg1 glycans 376:382 N-linked glycans 367:382 N-linked glycans 367:382 The degradation of ERAD substrates involves mannose trimming of N-linked glycans; however the precise mechanism of substrate recognition and sorting to the ERAD pathway is still poorly understood. 25655076 5 19 from ER 1054:1055 arg1 retrotranslocation 1026:1043 its retrotranslocation 1022:1043 its retrotranslocation from the ER to the cytosol 1022:1070 In the study we used ricin, a protein toxin that utilizes the ERAD pathway in its retrotranslocation from the ER to the cytosol, and a model misfolded protein, the pancreatic isoform of human β-secretase, BACE457. 25655076 5 19 from ER 1054:1055 arg1 pathway 1011:1017 the ERAD pathway 1002:1017 the ERAD pathway in its retrotranslocation from the ER to the cytosol 1002:1070 In the study we used ricin, a protein toxin that utilizes the ERAD pathway in its retrotranslocation from the ER to the cytosol, and a model misfolded protein, the pancreatic isoform of human β-secretase, BACE457. 25655076 8 20 theme transmembrane 1524:1536 arg1 regions 1538:1544 hydrophobic transmembrane regions 1512:1544 hydrophobic transmembrane regions of misfolded ERAD substrates 1512:1573 Moreover, EDEM proteins can bind hydrophobic transmembrane regions of misfolded ERAD substrates. 25655076 9 21 from cells 1666:1670 arg1 understanding 1613:1625 the general understanding 1601:1625 the general understanding of the regulation of ERAD in mammalian cells 1601:1670 These data contribute to the general understanding of the regulation of ERAD in mammalian cells. 25655076 7 22 theme high 1434:1437 arg1 hydrophobicity 1439:1452 a sufficiently high hydrophobicity 1419:1452 a sufficiently high hydrophobicity of protein determinants 1419:1476 CONCLUSIONS Our data provide the first evidence that recognition of ERAD substrates by EDEM1 and EDEM2 might be determined by a sufficiently high hydrophobicity of protein determinants. 25655076 1 23 theme endoplasmic 172:182 arg1 ER 195:196 ER 195:196 ER 195:196 BACKGROUND EDEM1 and EDEM2 are crucial regulators of the endoplasmic reticulum (ER)-associated degradation (ERAD) that extracts misfolded glycoproteins from the calnexin chaperone system. 25655076 1 23 theme endoplasmic 172:182 arg1 reticulum 184:192 the endoplasmic reticulum 168:192 the endoplasmic reticulum (ER)-associated degradation (ERAD) 168:227 BACKGROUND EDEM1 and EDEM2 are crucial regulators of the endoplasmic reticulum (ER)-associated degradation (ERAD) that extracts misfolded glycoproteins from the calnexin chaperone system. 25655076 2 24 theme sorting 444:450 arg1 mechanism 405:413 the precise mechanism 393:413 the precise mechanism of substrate recognition and sorting to the ERAD pathway 393:470 The degradation of ERAD substrates involves mannose trimming of N-linked glycans; however the precise mechanism of substrate recognition and sorting to the ERAD pathway is still poorly understood. 25655076 5 25 theme human 1130:1134 arg1 β-secretase 1136:1146 human β-secretase 1130:1146 human β-secretase 1130:1146 In the study we used ricin, a protein toxin that utilizes the ERAD pathway in its retrotranslocation from the ER to the cytosol, and a model misfolded protein, the pancreatic isoform of human β-secretase, BACE457. 25655076 5 25 theme human 1130:1134 arg1 BACE457 1149:1155 BACE457 1149:1155 BACE457 1149:1155 In the study we used ricin, a protein toxin that utilizes the ERAD pathway in its retrotranslocation from the ER to the cytosol, and a model misfolded protein, the pancreatic isoform of human β-secretase, BACE457. 25655076 6 26 theme proteins 1204:1211 arg1 regions 1187:1193 the hydrophobic regions 1171:1193 the hydrophobic regions of these proteins 1171:1211 Mutations in the hydrophobic regions of these proteins allowed us to obtain mutated forms with increased and decreased hydrophobicity. 25655076 1 27 gly glycoproteins 253:265 arg1 glycoproteins 253:265 misfolded glycoproteins 243:265 misfolded glycoproteins 243:265 BACKGROUND EDEM1 and EDEM2 are crucial regulators of the endoplasmic reticulum (ER)-associated degradation (ERAD) that extracts misfolded glycoproteins from the calnexin chaperone system. 25655076 1 28 theme reticulum 184:192 arg1 ERAD 223:226 ERAD 223:226 ERAD 223:226 BACKGROUND EDEM1 and EDEM2 are crucial regulators of the endoplasmic reticulum (ER)-associated degradation (ERAD) that extracts misfolded glycoproteins from the calnexin chaperone system. 25655076 1 28 theme reticulum 184:192 arg1 degradation 210:220 the endoplasmic reticulum (ER)-associated degradation 168:220 the endoplasmic reticulum (ER)-associated degradation (ERAD) 168:227 BACKGROUND EDEM1 and EDEM2 are crucial regulators of the endoplasmic reticulum (ER)-associated degradation (ERAD) that extracts misfolded glycoproteins from the calnexin chaperone system. 25655076 0 29 theme determinants 26:37 arg1 Hydrophobicity 0:13 Hydrophobicity 0:13 Hydrophobicity of protein determinants 0:37 Hydrophobicity of protein determinants influences the recognition of substrates by EDEM1 and EDEM2 in human cells. 25655076 5 30 theme β-secretase 1136:1146 arg1 isoform 1119:1125 the pancreatic isoform 1104:1125 the pancreatic isoform of human β-secretase, BACE457 1104:1155 In the study we used ricin, a protein toxin that utilizes the ERAD pathway in its retrotranslocation from the ER to the cytosol, and a model misfolded protein, the pancreatic isoform of human β-secretase, BACE457. 25655076 5 30 theme β-secretase 1136:1146 arg1 protein 1095:1101 a model misfolded protein 1077:1101 a model misfolded protein 1077:1101 In the study we used ricin, a protein toxin that utilizes the ERAD pathway in its retrotranslocation from the ER to the cytosol, and a model misfolded protein, the pancreatic isoform of human β-secretase, BACE457. 25655076 3 31 theme EDEM2 551:555 arg1 binding 557:563 EDEM2 binding 551:563 EDEM2 binding 551:563 It has previously been demonstrated that EDEM1 and EDEM2 binding does not require the trimming of substrate glycans or even ERAD substrate glycosylation, thus suggesting that both chaperones probably recognize misfolded regions of aberrant proteins. 25655076 5 32 from pathway 1011:1017 arg1 retrotranslocation 1026:1043 its retrotranslocation 1022:1043 its retrotranslocation from the ER to the cytosol 1022:1070 In the study we used ricin, a protein toxin that utilizes the ERAD pathway in its retrotranslocation from the ER to the cytosol, and a model misfolded protein, the pancreatic isoform of human β-secretase, BACE457. 25655076 5 32 from pathway 1011:1017 arg1 ER 1054:1055 the ER 1050:1055 the ER 1050:1055 In the study we used ricin, a protein toxin that utilizes the ERAD pathway in its retrotranslocation from the ER to the cytosol, and a model misfolded protein, the pancreatic isoform of human β-secretase, BACE457. 25655076 2 33 theme substrate 418:426 arg1 recognition 428:438 substrate recognition 418:438 substrate recognition 418:438 The degradation of ERAD substrates involves mannose trimming of N-linked glycans; however the precise mechanism of substrate recognition and sorting to the ERAD pathway is still poorly understood. 25655076 2 34 theme recognition 428:438 arg1 mechanism 405:413 the precise mechanism 393:413 the precise mechanism of substrate recognition and sorting to the ERAD pathway 393:470 The degradation of ERAD substrates involves mannose trimming of N-linked glycans; however the precise mechanism of substrate recognition and sorting to the ERAD pathway is still poorly understood. 25655076 1 35 theme calnexin 276:283 arg1 system 295:300 the calnexin chaperone system 272:300 the calnexin chaperone system 272:300 BACKGROUND EDEM1 and EDEM2 are crucial regulators of the endoplasmic reticulum (ER)-associated degradation (ERAD) that extracts misfolded glycoproteins from the calnexin chaperone system. 25655076 7 36 theme determinants 1465:1476 arg1 hydrophobicity 1439:1452 a sufficiently high hydrophobicity 1419:1452 a sufficiently high hydrophobicity of protein determinants 1419:1476 CONCLUSIONS Our data provide the first evidence that recognition of ERAD substrates by EDEM1 and EDEM2 might be determined by a sufficiently high hydrophobicity of protein determinants. 25655076 8 37 theme misfolded 1549:1557 arg1 substrates 1564:1573 misfolded ERAD substrates 1549:1573 misfolded ERAD substrates 1549:1573 Moreover, EDEM proteins can bind hydrophobic transmembrane regions of misfolded ERAD substrates. 25655076 9 38 theme ERAD 1648:1651 arg1 regulation 1634:1643 the regulation 1630:1643 the regulation of ERAD in mammalian cells 1630:1670 These data contribute to the general understanding of the regulation of ERAD in mammalian cells. 25655076 1 39 theme chaperone 285:293 arg1 system 295:300 the calnexin chaperone system 272:300 the calnexin chaperone system 272:300 BACKGROUND EDEM1 and EDEM2 are crucial regulators of the endoplasmic reticulum (ER)-associated degradation (ERAD) that extracts misfolded glycoproteins from the calnexin chaperone system. 25655076 0 40 from EDEM1 83:87 arg1 cells 108:112 human cells 102:112 human cells 102:112 Hydrophobicity of protein determinants influences the recognition of substrates by EDEM1 and EDEM2 in human cells. 25655076 4 41 theme substrate 790:798 arg1 recognition 800:810 the substrate recognition 786:810 the substrate recognition by EDEM1 and EDEM2 786:829 RESULTS In this work, we focused on the substrate recognition by EDEM1 and EDEM2, asking whether hydrophobicity of protein determinants might be important for these interactions in human cells. 25655076 2 42 theme glycans 376:382 arg1 trimming 355:362 mannose trimming 347:362 mannose trimming of N-linked glycans 347:382 The degradation of ERAD substrates involves mannose trimming of N-linked glycans; however the precise mechanism of substrate recognition and sorting to the ERAD pathway is still poorly understood. 25655076 5 43 used used 960:963 arg2 we 957:958 we 957:958 we 957:958 In the study we used ricin, a protein toxin that utilizes the ERAD pathway in its retrotranslocation from the ER to the cytosol, and a model misfolded protein, the pancreatic isoform of human β-secretase, BACE457. 25655076 8 44 theme substrates 1564:1573 arg1 regions 1538:1544 hydrophobic transmembrane regions 1512:1544 hydrophobic transmembrane regions of misfolded ERAD substrates 1512:1573 Moreover, EDEM proteins can bind hydrophobic transmembrane regions of misfolded ERAD substrates. 25655076 4 45 theme human 931:935 arg1 cells 937:941 human cells 931:941 human cells 931:941 RESULTS In this work, we focused on the substrate recognition by EDEM1 and EDEM2, asking whether hydrophobicity of protein determinants might be important for these interactions in human cells. 25655076 3 46 theme ERAD 624:627 arg1 substrate 629:637 even ERAD substrate 619:637 even ERAD substrate 619:637 It has previously been demonstrated that EDEM1 and EDEM2 binding does not require the trimming of substrate glycans or even ERAD substrate glycosylation, thus suggesting that both chaperones probably recognize misfolded regions of aberrant proteins. 25655076 7 47 theme ERAD 1361:1364 arg1 substrates 1366:1375 ERAD substrates 1361:1375 ERAD substrates 1361:1375 CONCLUSIONS Our data provide the first evidence that recognition of ERAD substrates by EDEM1 and EDEM2 might be determined by a sufficiently high hydrophobicity of protein determinants. 25655076 2 48 theme precise 397:403 arg1 mechanism 405:413 the precise mechanism 393:413 the precise mechanism of substrate recognition and sorting to the ERAD pathway 393:470 The degradation of ERAD substrates involves mannose trimming of N-linked glycans; however the precise mechanism of substrate recognition and sorting to the ERAD pathway is still poorly understood. 25655076 1 49 theme -associated 198:208 arg1 ERAD 223:226 ERAD 223:226 ERAD 223:226 BACKGROUND EDEM1 and EDEM2 are crucial regulators of the endoplasmic reticulum (ER)-associated degradation (ERAD) that extracts misfolded glycoproteins from the calnexin chaperone system. 25655076 1 49 theme -associated 198:208 arg1 degradation 210:220 the endoplasmic reticulum (ER)-associated degradation 168:220 the endoplasmic reticulum (ER)-associated degradation (ERAD) 168:227 BACKGROUND EDEM1 and EDEM2 are crucial regulators of the endoplasmic reticulum (ER)-associated degradation (ERAD) that extracts misfolded glycoproteins from the calnexin chaperone system. 25655076 2 50 theme ERAD 459:462 arg1 pathway 464:470 the ERAD pathway 455:470 the ERAD pathway 455:470 The degradation of ERAD substrates involves mannose trimming of N-linked glycans; however the precise mechanism of substrate recognition and sorting to the ERAD pathway is still poorly understood. 25655076 5 51 theme pancreatic 1108:1117 arg1 isoform 1119:1125 the pancreatic isoform 1104:1125 the pancreatic isoform of human β-secretase, BACE457 1104:1155 In the study we used ricin, a protein toxin that utilizes the ERAD pathway in its retrotranslocation from the ER to the cytosol, and a model misfolded protein, the pancreatic isoform of human β-secretase, BACE457. 25655076 5 51 theme pancreatic 1108:1117 arg1 protein 1095:1101 a model misfolded protein 1077:1101 a model misfolded protein 1077:1101 In the study we used ricin, a protein toxin that utilizes the ERAD pathway in its retrotranslocation from the ER to the cytosol, and a model misfolded protein, the pancreatic isoform of human β-secretase, BACE457. 25655076 4 52 from interactions 915:926 arg1 cells 937:941 human cells 931:941 human cells 931:941 RESULTS In this work, we focused on the substrate recognition by EDEM1 and EDEM2, asking whether hydrophobicity of protein determinants might be important for these interactions in human cells. 25655076 5 53 theme ERAD 1006:1009 arg1 pathway 1011:1017 the ERAD pathway 1002:1017 the ERAD pathway in its retrotranslocation from the ER to the cytosol 1002:1070 In the study we used ricin, a protein toxin that utilizes the ERAD pathway in its retrotranslocation from the ER to the cytosol, and a model misfolded protein, the pancreatic isoform of human β-secretase, BACE457. 25655076 8 54 theme hydrophobic 1512:1522 arg1 regions 1538:1544 hydrophobic transmembrane regions 1512:1544 hydrophobic transmembrane regions of misfolded ERAD substrates 1512:1573 Moreover, EDEM proteins can bind hydrophobic transmembrane regions of misfolded ERAD substrates. 25655076 9 55 from regulation 1634:1643 arg1 cells 1666:1670 mammalian cells 1656:1670 mammalian cells 1656:1670 These data contribute to the general understanding of the regulation of ERAD in mammalian cells. 25655076 6 56 theme decreased 1267:1275 arg1 hydrophobicity 1277:1290 increased and decreased hydrophobicity 1253:1290 increased and decreased hydrophobicity 1253:1290 Mutations in the hydrophobic regions of these proteins allowed us to obtain mutated forms with increased and decreased hydrophobicity. 25655076 6 57 theme hydrophobic 1175:1185 arg1 regions 1187:1193 the hydrophobic regions 1171:1193 the hydrophobic regions of these proteins 1171:1211 Mutations in the hydrophobic regions of these proteins allowed us to obtain mutated forms with increased and decreased hydrophobicity. 25655076 1 58 theme BACKGROUND 115:124 arg1 EDEM1 126:130 BACKGROUND EDEM1 115:130 BACKGROUND EDEM1 115:130 BACKGROUND EDEM1 and EDEM2 are crucial regulators of the endoplasmic reticulum (ER)-associated degradation (ERAD) that extracts misfolded glycoproteins from the calnexin chaperone system. 25655076 1 58 theme BACKGROUND 115:124 arg1 EDEM2 136:140 EDEM2 136:140 EDEM2 136:140 BACKGROUND EDEM1 and EDEM2 are crucial regulators of the endoplasmic reticulum (ER)-associated degradation (ERAD) that extracts misfolded glycoproteins from the calnexin chaperone system. 25655076 1 58 theme BACKGROUND 115:124 arg1 regulators 154:163 crucial regulators 146:163 crucial regulators of the endoplasmic reticulum (ER)-associated degradation (ERAD) that extracts misfolded glycoproteins from the calnexin chaperone system 146:300 BACKGROUND EDEM1 and EDEM2 are crucial regulators of the endoplasmic reticulum (ER)-associated degradation (ERAD) that extracts misfolded glycoproteins from the calnexin chaperone system. 25655076 3 59 theme glycans 608:614 arg1 trimming 586:593 the trimming 582:593 the trimming of substrate glycans 582:614 It has previously been demonstrated that EDEM1 and EDEM2 binding does not require the trimming of substrate glycans or even ERAD substrate glycosylation, thus suggesting that both chaperones probably recognize misfolded regions of aberrant proteins. 25655076 3 59 theme glycans 608:614 arg1 substrate 629:637 even ERAD substrate 619:637 even ERAD substrate 619:637 It has previously been demonstrated that EDEM1 and EDEM2 binding does not require the trimming of substrate glycans or even ERAD substrate glycosylation, thus suggesting that both chaperones probably recognize misfolded regions of aberrant proteins. 25655076 9 60 theme general 1605:1611 arg1 understanding 1613:1625 the general understanding 1601:1625 the general understanding of the regulation of ERAD in mammalian cells 1601:1670 These data contribute to the general understanding of the regulation of ERAD in mammalian cells. 25655076 7 61 theme first 1326:1330 arg1 evidence 1332:1339 the first evidence that recognition of ERAD substrates by EDEM1 and EDEM2 might be determined by a sufficiently high hydrophobicity of protein determinants 1322:1476 the first evidence that recognition of ERAD substrates by EDEM1 and EDEM2 might be determined by a sufficiently high hydrophobicity of protein determinants 1322:1476 CONCLUSIONS Our data provide the first evidence that recognition of ERAD substrates by EDEM1 and EDEM2 might be determined by a sufficiently high hydrophobicity of protein determinants. 25655076 7 62 dep CONCLUSIONS 1293:1303 arg1 provide 1314:1320 provide 1314:1320 provide the first evidence that recognition of ERAD substrates by EDEM1 and EDEM2 might be determined by a sufficiently high hydrophobicity of protein determinants 1314:1476 CONCLUSIONS Our data provide the first evidence that recognition of ERAD substrates by EDEM1 and EDEM2 might be determined by a sufficiently high hydrophobicity of protein determinants. 25655076 2 63 theme ERAD 322:325 arg1 substrates 327:336 ERAD substrates 322:336 ERAD substrates 322:336 The degradation of ERAD substrates involves mannose trimming of N-linked glycans; however the precise mechanism of substrate recognition and sorting to the ERAD pathway is still poorly understood. 25655076 7 64 theme substrates 1366:1375 arg1 recognition 1346:1356 recognition 1346:1356 recognition of ERAD substrates by EDEM1 and EDEM2 1346:1394 CONCLUSIONS Our data provide the first evidence that recognition of ERAD substrates by EDEM1 and EDEM2 might be determined by a sufficiently high hydrophobicity of protein determinants. 25655076 1 65 theme degradation 210:220 arg1 EDEM1 126:130 BACKGROUND EDEM1 115:130 BACKGROUND EDEM1 115:130 BACKGROUND EDEM1 and EDEM2 are crucial regulators of the endoplasmic reticulum (ER)-associated degradation (ERAD) that extracts misfolded glycoproteins from the calnexin chaperone system. 25655076 1 65 theme degradation 210:220 arg1 EDEM2 136:140 EDEM2 136:140 EDEM2 136:140 BACKGROUND EDEM1 and EDEM2 are crucial regulators of the endoplasmic reticulum (ER)-associated degradation (ERAD) that extracts misfolded glycoproteins from the calnexin chaperone system. 25655076 1 65 theme degradation 210:220 arg1 regulators 154:163 crucial regulators 146:163 crucial regulators of the endoplasmic reticulum (ER)-associated degradation (ERAD) that extracts misfolded glycoproteins from the calnexin chaperone system 146:300 BACKGROUND EDEM1 and EDEM2 are crucial regulators of the endoplasmic reticulum (ER)-associated degradation (ERAD) that extracts misfolded glycoproteins from the calnexin chaperone system. 25655076 6 66 theme increased 1253:1261 arg1 hydrophobicity 1277:1290 increased and decreased hydrophobicity 1253:1290 increased and decreased hydrophobicity 1253:1290 Mutations in the hydrophobic regions of these proteins allowed us to obtain mutated forms with increased and decreased hydrophobicity. 25655076 3 67 theme even 619:622 arg1 substrate 629:637 even ERAD substrate 619:637 even ERAD substrate 619:637 It has previously been demonstrated that EDEM1 and EDEM2 binding does not require the trimming of substrate glycans or even ERAD substrate glycosylation, thus suggesting that both chaperones probably recognize misfolded regions of aberrant proteins. 25655076 4 68 dep RESULTS 750:756 arg1 focused 775:781 focused 775:781 focused 775:781 RESULTS In this work, we focused on the substrate recognition by EDEM1 and EDEM2, asking whether hydrophobicity of protein determinants might be important for these interactions in human cells. 25655076 0 69 from EDEM2 93:97 arg1 cells 108:112 human cells 102:112 human cells 102:112 Hydrophobicity of protein determinants influences the recognition of substrates by EDEM1 and EDEM2 in human cells. 25655076 3 70 theme substrate 598:606 arg1 glycans 608:614 substrate glycans 598:614 substrate glycans 598:614 It has previously been demonstrated that EDEM1 and EDEM2 binding does not require the trimming of substrate glycans or even ERAD substrate glycosylation, thus suggesting that both chaperones probably recognize misfolded regions of aberrant proteins. 25655076 2 71 theme N-linked 367:374 arg1 glycans 376:382 N-linked glycans 367:382 N-linked glycans 367:382 The degradation of ERAD substrates involves mannose trimming of N-linked glycans; however the precise mechanism of substrate recognition and sorting to the ERAD pathway is still poorly understood. 25655076 6 72 with forms 1242:1246 arg1 hydrophobicity 1277:1290 increased and decreased hydrophobicity 1253:1290 increased and decreased hydrophobicity 1253:1290 Mutations in the hydrophobic regions of these proteins allowed us to obtain mutated forms with increased and decreased hydrophobicity. 25655076 2 73 theme substrates 327:336 arg1 degradation 307:317 The degradation 303:317 The degradation of ERAD substrates 303:336 The degradation of ERAD substrates involves mannose trimming of N-linked glycans; however the precise mechanism of substrate recognition and sorting to the ERAD pathway is still poorly understood. 25655076 0 74 theme substrates 69:78 arg1 recognition 54:64 the recognition 50:64 the recognition of substrates by EDEM1 and EDEM2 in human cells 50:112 Hydrophobicity of protein determinants influences the recognition of substrates by EDEM1 and EDEM2 in human cells. 25655076 5 75 theme model 1079:1083 arg1 isoform 1119:1125 the pancreatic isoform 1104:1125 the pancreatic isoform of human β-secretase, BACE457 1104:1155 In the study we used ricin, a protein toxin that utilizes the ERAD pathway in its retrotranslocation from the ER to the cytosol, and a model misfolded protein, the pancreatic isoform of human β-secretase, BACE457. 25655076 5 75 theme model 1079:1083 arg1 protein 1095:1101 a model misfolded protein 1077:1101 a model misfolded protein 1077:1101 In the study we used ricin, a protein toxin that utilizes the ERAD pathway in its retrotranslocation from the ER to the cytosol, and a model misfolded protein, the pancreatic isoform of human β-secretase, BACE457. 25655076 0 76 theme protein 18:24 arg1 determinants 26:37 protein determinants 18:37 protein determinants 18:37 Hydrophobicity of protein determinants influences the recognition of substrates by EDEM1 and EDEM2 in human cells. 25655076 6 77 from Mutations 1158:1166 arg1 regions 1187:1193 the hydrophobic regions 1171:1193 the hydrophobic regions of these proteins 1171:1211 Mutations in the hydrophobic regions of these proteins allowed us to obtain mutated forms with increased and decreased hydrophobicity. 25655076 8 78 theme ERAD 1559:1562 arg1 substrates 1564:1573 misfolded ERAD substrates 1549:1573 misfolded ERAD substrates 1549:1573 Moreover, EDEM proteins can bind hydrophobic transmembrane regions of misfolded ERAD substrates. 25536377 5 0 theme GlcNAc 767:772 arg1 addition 746:753 the addition 742:753 the addition of a single GlcNAc to arginine 742:784 Although the addition of a single GlcNAc to arginine is a seemingly slight alteration, the impact of NleB is considerable as arginine in this location is critical for death domain interactions and death receptor induced apoptosis. 25536377 5 0 theme GlcNAc 767:772 arg1 alteration 808:817 a seemingly slight alteration 789:817 a seemingly slight alteration 789:817 Although the addition of a single GlcNAc to arginine is a seemingly slight alteration, the impact of NleB is considerable as arginine in this location is critical for death domain interactions and death receptor induced apoptosis. 25536377 3 1 attach attachment 481:490 arg2 GlcNAc 516:521 GlcNAc 516:521 GlcNAc 516:521 NleB mediated post-translational modification of death domain containing adaptor proteins by the covalent attachment of N-acetylglucosamine (GlcNAc) to a conserved arginine in the death domain. 25536377 3 1 attach attachment 481:490 arg1 arginine 539:546 a conserved arginine 527:546 a conserved arginine in the death domain 527:566 NleB mediated post-translational modification of death domain containing adaptor proteins by the covalent attachment of N-acetylglucosamine (GlcNAc) to a conserved arginine in the death domain. 25536377 3 1 attach attachment 481:490 arg2 N-acetylglucosamine 495:513 N-acetylglucosamine 495:513 N-acetylglucosamine (GlcNAc) 495:522 NleB mediated post-translational modification of death domain containing adaptor proteins by the covalent attachment of N-acetylglucosamine (GlcNAc) to a conserved arginine in the death domain. 25536377 3 2 from arginine 539:546 arg1 domain 561:566 the death domain 551:566 the death domain 551:566 NleB mediated post-translational modification of death domain containing adaptor proteins by the covalent attachment of N-acetylglucosamine (GlcNAc) to a conserved arginine in the death domain. 25536377 2 3 theme system 346:351 arg1 NleB 369:372 the type III secretion system (T3SS) effector NleB 323:372 the type III secretion system (T3SS) effector NleB 323:372 Recently, we observed that EPEC blocks cell death using the type III secretion system (T3SS) effector NleB. 25536377 6 4 theme cell 983:986 arg1 death 988:992 cell death 983:992 cell death 983:992 Hence, by blocking cell death, NleB promotes enterocyte survival and thereby prolongs EPEC attachment to the gut epithelium. 25536377 5 5 theme induced 945:951 arg1 apoptosis 953:961 death receptor induced apoptosis 930:961 death receptor induced apoptosis 930:961 Although the addition of a single GlcNAc to arginine is a seemingly slight alteration, the impact of NleB is considerable as arginine in this location is critical for death domain interactions and death receptor induced apoptosis. 25536377 4 6 theme arginine 595:602 arg1 glycosylation 578:590 N-linked glycosylation 569:590 N-linked glycosylation of arginine 569:602 N-linked glycosylation of arginine has not previously been reported in mammalian cell biology and the precise biochemistry of this modification is not yet defined. 25536377 4 7 theme modification 700:711 arg1 biochemistry 679:690 the precise biochemistry 667:690 the precise biochemistry of this modification 667:711 N-linked glycosylation of arginine has not previously been reported in mammalian cell biology and the precise biochemistry of this modification is not yet defined. 25536377 3 8 theme N-acetylglucosamine 495:513 arg1 attachment 481:490 the covalent attachment 468:490 the covalent attachment of N-acetylglucosamine (GlcNAc) to a conserved arginine in the death domain 468:566 NleB mediated post-translational modification of death domain containing adaptor proteins by the covalent attachment of N-acetylglucosamine (GlcNAc) to a conserved arginine in the death domain. 25536377 5 9 theme slight 801:806 arg1 addition 746:753 the addition 742:753 the addition of a single GlcNAc to arginine 742:784 Although the addition of a single GlcNAc to arginine is a seemingly slight alteration, the impact of NleB is considerable as arginine in this location is critical for death domain interactions and death receptor induced apoptosis. 25536377 5 9 theme slight 801:806 arg1 alteration 808:817 a seemingly slight alteration 789:817 a seemingly slight alteration 789:817 Although the addition of a single GlcNAc to arginine is a seemingly slight alteration, the impact of NleB is considerable as arginine in this location is critical for death domain interactions and death receptor induced apoptosis. 25536377 3 10 theme conserved 529:537 arg1 arginine 539:546 a conserved arginine 527:546 a conserved arginine in the death domain 527:566 NleB mediated post-translational modification of death domain containing adaptor proteins by the covalent attachment of N-acetylglucosamine (GlcNAc) to a conserved arginine in the death domain. 25536377 1 11 theme damage 175:180 arg1 devoid 135:140 devoid 135:140 devoid 135:140 Infections with enteropathogenic Escherichia coli (EPEC) are remarkably devoid of gut inflammation and necrotic damage compared to infections caused by invasive pathogens such as Salmonella and Shigella. 25536377 0 12 from Escherichia 45:55 arg1 sweetener 13:21 A surprising sweetener 0:21 A surprising sweetener from enteropathogenic Escherichia coli 0:60 A surprising sweetener from enteropathogenic Escherichia coli. 25536377 4 13 gly glycosylation 578:590 arg1 arginine 595:602 arginine 595:602 arginine 595:602 N-linked glycosylation of arginine has not previously been reported in mammalian cell biology and the precise biochemistry of this modification is not yet defined. 25536377 4 13 gly glycosylation 578:590 arg1 biology 655:661 mammalian cell biology 640:661 mammalian cell biology 640:661 N-linked glycosylation of arginine has not previously been reported in mammalian cell biology and the precise biochemistry of this modification is not yet defined. 25536377 6 14 theme gut 1073:1075 arg1 epithelium 1077:1086 the gut epithelium 1069:1086 the gut epithelium 1069:1086 Hence, by blocking cell death, NleB promotes enterocyte survival and thereby prolongs EPEC attachment to the gut epithelium. 25536377 3 15 theme adaptor 448:454 arg1 proteins 456:463 adaptor proteins 448:463 adaptor proteins 448:463 NleB mediated post-translational modification of death domain containing adaptor proteins by the covalent attachment of N-acetylglucosamine (GlcNAc) to a conserved arginine in the death domain. 25536377 0 16 theme surprising 2:11 arg1 sweetener 13:21 A surprising sweetener 0:21 A surprising sweetener from enteropathogenic Escherichia coli 0:60 A surprising sweetener from enteropathogenic Escherichia coli. 25536377 5 17 theme receptor 936:943 arg1 apoptosis 953:961 death receptor induced apoptosis 930:961 death receptor induced apoptosis 930:961 Although the addition of a single GlcNAc to arginine is a seemingly slight alteration, the impact of NleB is considerable as arginine in this location is critical for death domain interactions and death receptor induced apoptosis. 25536377 3 18 theme death 424:428 arg1 domain 430:435 death domain 424:435 death domain containing adaptor proteins 424:463 NleB mediated post-translational modification of death domain containing adaptor proteins by the covalent attachment of N-acetylglucosamine (GlcNAc) to a conserved arginine in the death domain. 25536377 5 19 theme death 930:934 arg1 apoptosis 953:961 death receptor induced apoptosis 930:961 death receptor induced apoptosis 930:961 Although the addition of a single GlcNAc to arginine is a seemingly slight alteration, the impact of NleB is considerable as arginine in this location is critical for death domain interactions and death receptor induced apoptosis. 25536377 3 20 theme domain 430:435 arg1 modification 408:419 post-translational modification 389:419 post-translational modification of death domain containing adaptor proteins by the covalent attachment of N-acetylglucosamine (GlcNAc) to a conserved arginine in the death domain 389:566 NleB mediated post-translational modification of death domain containing adaptor proteins by the covalent attachment of N-acetylglucosamine (GlcNAc) to a conserved arginine in the death domain. 25536377 3 21 theme death 555:559 arg1 domain 561:566 the death domain 551:566 the death domain 551:566 NleB mediated post-translational modification of death domain containing adaptor proteins by the covalent attachment of N-acetylglucosamine (GlcNAc) to a conserved arginine in the death domain. 25536377 4 22 theme mammalian 640:648 arg1 biology 655:661 mammalian cell biology 640:661 mammalian cell biology 640:661 N-linked glycosylation of arginine has not previously been reported in mammalian cell biology and the precise biochemistry of this modification is not yet defined. 25536377 4 23 theme N-linked 569:576 arg1 glycosylation 578:590 N-linked glycosylation 569:590 N-linked glycosylation of arginine 569:602 N-linked glycosylation of arginine has not previously been reported in mammalian cell biology and the precise biochemistry of this modification is not yet defined. 25536377 1 24 theme necrotic 166:173 arg1 damage 175:180 necrotic damage 166:180 necrotic damage 166:180 Infections with enteropathogenic Escherichia coli (EPEC) are remarkably devoid of gut inflammation and necrotic damage compared to infections caused by invasive pathogens such as Salmonella and Shigella. 25536377 3 25 theme covalent 472:479 arg1 attachment 481:490 the covalent attachment 468:490 the covalent attachment of N-acetylglucosamine (GlcNAc) to a conserved arginine in the death domain 468:566 NleB mediated post-translational modification of death domain containing adaptor proteins by the covalent attachment of N-acetylglucosamine (GlcNAc) to a conserved arginine in the death domain. 25536377 5 26 theme death 900:904 arg1 interactions 913:924 death domain interactions 900:924 death domain interactions 900:924 Although the addition of a single GlcNAc to arginine is a seemingly slight alteration, the impact of NleB is considerable as arginine in this location is critical for death domain interactions and death receptor induced apoptosis. 25536377 5 27 theme NleB 834:837 arg1 impact 824:829 the impact 820:829 the impact of NleB 820:837 Although the addition of a single GlcNAc to arginine is a seemingly slight alteration, the impact of NleB is considerable as arginine in this location is critical for death domain interactions and death receptor induced apoptosis. 25536377 5 27 theme NleB 834:837 arg1 considerable 842:853 considerable 842:853 considerable 842:853 Although the addition of a single GlcNAc to arginine is a seemingly slight alteration, the impact of NleB is considerable as arginine in this location is critical for death domain interactions and death receptor induced apoptosis. 25536377 2 28 theme effector 360:367 arg1 NleB 369:372 the type III secretion system (T3SS) effector NleB 323:372 the type III secretion system (T3SS) effector NleB 323:372 Recently, we observed that EPEC blocks cell death using the type III secretion system (T3SS) effector NleB. 25536377 1 29 theme invasive 215:222 arg1 Salmonella 242:251 Salmonella 242:251 Salmonella 242:251 Infections with enteropathogenic Escherichia coli (EPEC) are remarkably devoid of gut inflammation and necrotic damage compared to infections caused by invasive pathogens such as Salmonella and Shigella. 25536377 1 29 theme invasive 215:222 arg1 Shigella 257:264 Shigella 257:264 Shigella 257:264 Infections with enteropathogenic Escherichia coli (EPEC) are remarkably devoid of gut inflammation and necrotic damage compared to infections caused by invasive pathogens such as Salmonella and Shigella. 25536377 1 29 theme invasive 215:222 arg1 pathogens 224:232 invasive pathogens 215:232 invasive pathogens such as Salmonella and Shigella 215:264 Infections with enteropathogenic Escherichia coli (EPEC) are remarkably devoid of gut inflammation and necrotic damage compared to infections caused by invasive pathogens such as Salmonella and Shigella. 25536377 4 30 theme cell 650:653 arg1 biology 655:661 mammalian cell biology 640:661 mammalian cell biology 640:661 N-linked glycosylation of arginine has not previously been reported in mammalian cell biology and the precise biochemistry of this modification is not yet defined. 25536377 1 31 with Infections 63:72 arg1 EPEC 114:117 EPEC 114:117 EPEC 114:117 Infections with enteropathogenic Escherichia coli (EPEC) are remarkably devoid of gut inflammation and necrotic damage compared to infections caused by invasive pathogens such as Salmonella and Shigella. 25536377 1 31 with Infections 63:72 arg1 coli 108:111 Escherichia coli 96:111 enteropathogenic Escherichia coli (EPEC) 79:118 Infections with enteropathogenic Escherichia coli (EPEC) are remarkably devoid of gut inflammation and necrotic damage compared to infections caused by invasive pathogens such as Salmonella and Shigella. 25536377 0 32 dep Escherichia 45:55 arg1 coli 57:60 coli 57:60 coli 57:60 A surprising sweetener from enteropathogenic Escherichia coli. 25536377 2 33 theme secretion 336:344 arg1 T3SS 354:357 T3SS 354:357 T3SS 354:357 Recently, we observed that EPEC blocks cell death using the type III secretion system (T3SS) effector NleB. 25536377 2 33 theme secretion 336:344 arg1 system 346:351 the type III secretion system 323:351 the type III secretion system (T3SS) effector NleB 323:372 Recently, we observed that EPEC blocks cell death using the type III secretion system (T3SS) effector NleB. 25536377 3 34 theme post-translational 389:406 arg1 modification 408:419 post-translational modification 389:419 post-translational modification of death domain containing adaptor proteins by the covalent attachment of N-acetylglucosamine (GlcNAc) to a conserved arginine in the death domain 389:566 NleB mediated post-translational modification of death domain containing adaptor proteins by the covalent attachment of N-acetylglucosamine (GlcNAc) to a conserved arginine in the death domain. 25536377 4 35 theme precise 671:677 arg1 biochemistry 679:690 the precise biochemistry 667:690 the precise biochemistry of this modification 667:711 N-linked glycosylation of arginine has not previously been reported in mammalian cell biology and the precise biochemistry of this modification is not yet defined. 25536377 2 36 theme type 327:330 arg1 T3SS 354:357 T3SS 354:357 T3SS 354:357 Recently, we observed that EPEC blocks cell death using the type III secretion system (T3SS) effector NleB. 25536377 2 36 theme type 327:330 arg1 system 346:351 the type III secretion system 323:351 the type III secretion system (T3SS) effector NleB 323:372 Recently, we observed that EPEC blocks cell death using the type III secretion system (T3SS) effector NleB. 25536377 2 37 theme cell 306:309 arg1 death 311:315 cell death 306:315 cell death using the type III secretion system (T3SS) effector NleB 306:372 Recently, we observed that EPEC blocks cell death using the type III secretion system (T3SS) effector NleB. 25536377 6 38 theme enterocyte 1009:1018 arg1 survival 1020:1027 enterocyte survival 1009:1027 enterocyte survival 1009:1027 Hence, by blocking cell death, NleB promotes enterocyte survival and thereby prolongs EPEC attachment to the gut epithelium. 25536377 6 39 theme EPEC 1050:1053 arg1 attachment 1055:1064 EPEC attachment 1050:1064 EPEC attachment 1050:1064 Hence, by blocking cell death, NleB promotes enterocyte survival and thereby prolongs EPEC attachment to the gut epithelium. 25536377 5 40 from arginine 858:865 arg1 location 875:882 this location 870:882 this location 870:882 Although the addition of a single GlcNAc to arginine is a seemingly slight alteration, the impact of NleB is considerable as arginine in this location is critical for death domain interactions and death receptor induced apoptosis. 25536377 5 41 theme domain 906:911 arg1 interactions 913:924 death domain interactions 900:924 death domain interactions 900:924 Although the addition of a single GlcNAc to arginine is a seemingly slight alteration, the impact of NleB is considerable as arginine in this location is critical for death domain interactions and death receptor induced apoptosis. 25536377 3 42 contain containing 437:446 arg1 domain 430:435 death domain 424:435 death domain containing adaptor proteins 424:463 NleB mediated post-translational modification of death domain containing adaptor proteins by the covalent attachment of N-acetylglucosamine (GlcNAc) to a conserved arginine in the death domain. 25536377 3 42 contain containing 437:446 arg2 proteins 456:463 adaptor proteins 448:463 adaptor proteins 448:463 NleB mediated post-translational modification of death domain containing adaptor proteins by the covalent attachment of N-acetylglucosamine (GlcNAc) to a conserved arginine in the death domain. 25536377 1 43 theme gut 145:147 arg1 inflammation 149:160 gut inflammation 145:160 gut inflammation 145:160 Infections with enteropathogenic Escherichia coli (EPEC) are remarkably devoid of gut inflammation and necrotic damage compared to infections caused by invasive pathogens such as Salmonella and Shigella. 25536377 5 44 theme single 760:765 arg1 GlcNAc 767:772 a single GlcNAc 758:772 a single GlcNAc 758:772 Although the addition of a single GlcNAc to arginine is a seemingly slight alteration, the impact of NleB is considerable as arginine in this location is critical for death domain interactions and death receptor induced apoptosis. 25536377 4 45 link N-linked 569:576 arg1 glycosylation 578:590 N-linked glycosylation 569:590 N-linked glycosylation of arginine 569:602 N-linked glycosylation of arginine has not previously been reported in mammalian cell biology and the precise biochemistry of this modification is not yet defined. 25536377 1 46 theme inflammation 149:160 arg1 devoid 135:140 devoid 135:140 devoid 135:140 Infections with enteropathogenic Escherichia coli (EPEC) are remarkably devoid of gut inflammation and necrotic damage compared to infections caused by invasive pathogens such as Salmonella and Shigella. 25395220 0 0 theme product 80:86 arg1 quality 88:94 product quality 80:94 product quality 80:94 Uncovering methods for the prevention of protein aggregation and improvement of product quality in a transient expression system. 25395220 9 1 theme general 1571:1577 arg1 approach 1579:1586 a general approach 1569:1586 a general approach to enhance product quality from transient expression systems 1569:1647 These techniques have produced a similar improvement in product quality with a variety of other molecules, suggesting that this may be a general approach to enhance product quality from transient expression systems. 25395220 9 1 theme general 1571:1577 arg1 this 1557:1560 this 1557:1560 this 1557:1560 These techniques have produced a similar improvement in product quality with a variety of other molecules, suggesting that this may be a general approach to enhance product quality from transient expression systems. 25395220 6 2 theme same 1043:1046 arg1 elements 1048:1055 the same elements 1039:1055 the same elements as the gene containing plasmid 1039:1086 For gene dosing to have this effect, it is critical for the carrier DNA to be an empty vector containing the same elements as the gene containing plasmid. 25395220 4 3 theme undesirable 589:599 arg1 products 601:608 undesirable products 589:608 undesirable products 589:608 The removal of undesirable products, such as aggregation, depends primarily on purification, requiring additional cumbersome steps, which can lead to a lower product yield and longer timelines. 25395220 4 3 theme undesirable 589:599 arg1 aggregation 619:629 aggregation 619:629 aggregation 619:629 The removal of undesirable products, such as aggregation, depends primarily on purification, requiring additional cumbersome steps, which can lead to a lower product yield and longer timelines. 25395220 5 4 theme secreted 893:900 arg1 molecules 902:910 secreted molecules 893:910 secreted molecules prone to aggregation 893:931 In this study, we show that reducing the level of transcription by transfecting at a lower gene dose improves the quality of secreted molecules prone to aggregation. 25395220 9 5 theme transient 1620:1628 arg1 systems 1641:1647 transient expression systems 1620:1647 transient expression systems 1620:1647 These techniques have produced a similar improvement in product quality with a variety of other molecules, suggesting that this may be a general approach to enhance product quality from transient expression systems. 25395220 2 6 theme rapid 353:357 arg1 timeline 359:366 its rapid timeline 349:366 its rapid timeline 349:366 Transient expression has become increasingly popular in recent years due to its rapid timeline and improvements in expression level. 25395220 1 7 theme research 257:264 arg1 systems 151:157 Mammalian expression systems 130:157 Mammalian expression systems 130:157 Mammalian expression systems are used routinely for the production of recombinant proteins as therapeutic molecules as well as research tools. 25395220 1 7 theme research 257:264 arg1 tools 266:270 research tools 257:270 therapeutic molecules as well as research tools 224:270 Mammalian expression systems are used routinely for the production of recombinant proteins as therapeutic molecules as well as research tools. 25395220 7 8 theme temperature 1137:1147 arg1 shift 1149:1153 a temperature shift 1135:1153 a temperature shift to hypothermic conditions during production 1135:1197 This approach can be used in combination with a temperature shift to hypothermic conditions during production to enhance the effect. 25395220 6 9 contain containing 1028:1037 arg1 vector 1021:1026 an empty vector 1012:1026 an empty vector containing the same elements as the gene containing plasmid 1012:1086 For gene dosing to have this effect, it is critical for the carrier DNA to be an empty vector containing the same elements as the gene containing plasmid. 25395220 6 9 contain containing 1028:1037 arg1 DNA 1002:1004 the carrier DNA 990:1004 the carrier DNA 990:1004 For gene dosing to have this effect, it is critical for the carrier DNA to be an empty vector containing the same elements as the gene containing plasmid. 25395220 6 9 contain containing 1028:1037 arg2 elements 1048:1055 the same elements 1039:1055 the same elements as the gene containing plasmid 1039:1086 For gene dosing to have this effect, it is critical for the carrier DNA to be an empty vector containing the same elements as the gene containing plasmid. 25395220 8 10 with products 1306:1313 arg1 quality 1337:1343 overall superior quality 1320:1343 overall superior quality 1320:1343 The observed improvements not only minimized aggregation levels, but also generated products with overall superior quality, including more homogeneous signal peptide cleavage and N-linked glycosylation profiles. 25395220 2 11 from years 336:340 arg1 popular 318:324 popular 318:324 popular 318:324 Transient expression has become increasingly popular in recent years due to its rapid timeline and improvements in expression level. 25395220 1 12 used used 163:166 arg2 systems 151:157 Mammalian expression systems 130:157 Mammalian expression systems 130:157 Mammalian expression systems are used routinely for the production of recombinant proteins as therapeutic molecules as well as research tools. 25395220 1 12 used used 163:166 arg2 tools 266:270 research tools 257:270 therapeutic molecules as well as research tools 224:270 Mammalian expression systems are used routinely for the production of recombinant proteins as therapeutic molecules as well as research tools. 25395220 1 12 used used 163:166 arg2 molecules 236:244 therapeutic molecules 224:244 therapeutic molecules as well as research tools 224:270 Mammalian expression systems are used routinely for the production of recombinant proteins as therapeutic molecules as well as research tools. 25395220 9 13 theme molecules 1530:1538 arg1 molecules 1530:1538 other molecules 1524:1538 other molecules 1524:1538 These techniques have produced a similar improvement in product quality with a variety of other molecules, suggesting that this may be a general approach to enhance product quality from transient expression systems. 25395220 9 13 theme molecules 1530:1538 arg1 variety 1513:1519 a variety 1511:1519 a variety of other molecules 1511:1538 These techniques have produced a similar improvement in product quality with a variety of other molecules, suggesting that this may be a general approach to enhance product quality from transient expression systems. 25395220 0 14 theme quality 88:94 arg1 improvement 65:75 improvement 65:75 improvement of product quality 65:94 Uncovering methods for the prevention of protein aggregation and improvement of product quality in a transient expression system. 25395220 0 14 theme quality 88:94 arg1 prevention 27:36 the prevention 23:36 the prevention of protein aggregation 23:59 Uncovering methods for the prevention of protein aggregation and improvement of product quality in a transient expression system. 25395220 9 15 theme product 1490:1496 arg1 quality 1498:1504 product quality 1490:1504 product quality 1490:1504 These techniques have produced a similar improvement in product quality with a variety of other molecules, suggesting that this may be a general approach to enhance product quality from transient expression systems. 25395220 9 16 theme other 1524:1528 arg1 molecules 1530:1538 other molecules 1524:1538 other molecules 1524:1538 These techniques have produced a similar improvement in product quality with a variety of other molecules, suggesting that this may be a general approach to enhance product quality from transient expression systems. 25395220 3 17 theme little 556:561 arg1 attention 563:571 little attention 556:571 little attention 556:571 While improvements to transient expression systems have focused mainly on the level of protein expression, the aspect of protein quality has received little attention. 25395220 3 18 theme protein 493:499 arg1 expression 501:510 protein expression 493:510 protein expression 493:510 While improvements to transient expression systems have focused mainly on the level of protein expression, the aspect of protein quality has received little attention. 25395220 0 19 theme transient 101:109 arg1 system 122:127 a transient expression system 99:127 a transient expression system 99:127 Uncovering methods for the prevention of protein aggregation and improvement of product quality in a transient expression system. 25395220 9 20 theme similar 1467:1473 arg1 improvement 1475:1485 a similar improvement 1465:1485 a similar improvement in product quality with a variety of other molecules 1465:1538 These techniques have produced a similar improvement in product quality with a variety of other molecules, suggesting that this may be a general approach to enhance product quality from transient expression systems. 25395220 5 21 theme transcription 818:830 arg1 level 809:813 the level 805:813 the level of transcription 805:830 In this study, we show that reducing the level of transcription by transfecting at a lower gene dose improves the quality of secreted molecules prone to aggregation. 25395220 3 22 theme quality 535:541 arg1 aspect 517:522 the aspect 513:522 the aspect of protein quality 513:541 While improvements to transient expression systems have focused mainly on the level of protein expression, the aspect of protein quality has received little attention. 25395220 3 23 theme expression 438:447 arg1 systems 449:455 transient expression systems 428:455 transient expression systems 428:455 While improvements to transient expression systems have focused mainly on the level of protein expression, the aspect of protein quality has received little attention. 25395220 4 24 theme products 601:608 arg1 removal 578:584 The removal 574:584 The removal of undesirable products, such as aggregation, 574:630 The removal of undesirable products, such as aggregation, depends primarily on purification, requiring additional cumbersome steps, which can lead to a lower product yield and longer timelines. 25395220 8 25 link N-linked 1401:1408 arg1 profiles 1424:1431 N-linked glycosylation profiles 1401:1431 N-linked glycosylation profiles 1401:1431 The observed improvements not only minimized aggregation levels, but also generated products with overall superior quality, including more homogeneous signal peptide cleavage and N-linked glycosylation profiles. 25395220 2 26 from timeline 359:366 arg1 level 399:403 expression level 388:403 expression level 388:403 Transient expression has become increasingly popular in recent years due to its rapid timeline and improvements in expression level. 25395220 2 27 theme Transient 273:281 arg1 expression 283:292 Transient expression 273:292 Transient expression 273:292 Transient expression has become increasingly popular in recent years due to its rapid timeline and improvements in expression level. 25395220 6 28 theme gene 938:941 arg1 dosing 943:948 gene dosing 938:948 gene dosing to have this effect 938:968 For gene dosing to have this effect, it is critical for the carrier DNA to be an empty vector containing the same elements as the gene containing plasmid. 25395220 7 29 theme hypothermic 1158:1168 arg1 conditions 1170:1179 hypothermic conditions 1158:1179 hypothermic conditions 1158:1179 This approach can be used in combination with a temperature shift to hypothermic conditions during production to enhance the effect. 25395220 2 30 theme recent 329:334 arg1 years 336:340 recent years 329:340 recent years due to its rapid timeline and improvements in expression level 329:403 Transient expression has become increasingly popular in recent years due to its rapid timeline and improvements in expression level. 25395220 6 31 theme empty 1015:1019 arg1 vector 1021:1026 an empty vector 1012:1026 an empty vector containing the same elements as the gene containing plasmid 1012:1086 For gene dosing to have this effect, it is critical for the carrier DNA to be an empty vector containing the same elements as the gene containing plasmid. 25395220 6 31 theme empty 1015:1019 arg1 DNA 1002:1004 the carrier DNA 990:1004 the carrier DNA 990:1004 For gene dosing to have this effect, it is critical for the carrier DNA to be an empty vector containing the same elements as the gene containing plasmid. 25395220 2 32 theme expression 388:397 arg1 level 399:403 expression level 388:403 expression level 388:403 Transient expression has become increasingly popular in recent years due to its rapid timeline and improvements in expression level. 25395220 9 33 with improvement 1475:1485 arg1 molecules 1530:1538 other molecules 1524:1538 other molecules 1524:1538 These techniques have produced a similar improvement in product quality with a variety of other molecules, suggesting that this may be a general approach to enhance product quality from transient expression systems. 25395220 9 33 with improvement 1475:1485 arg1 variety 1513:1519 a variety 1511:1519 a variety of other molecules 1511:1538 These techniques have produced a similar improvement in product quality with a variety of other molecules, suggesting that this may be a general approach to enhance product quality from transient expression systems. 25395220 2 34 from improvements 372:383 arg1 level 399:403 expression level 388:403 expression level 388:403 Transient expression has become increasingly popular in recent years due to its rapid timeline and improvements in expression level. 25395220 4 35 theme product 732:738 arg1 yield 740:744 a lower product yield 724:744 a lower product yield 724:744 The removal of undesirable products, such as aggregation, depends primarily on purification, requiring additional cumbersome steps, which can lead to a lower product yield and longer timelines. 25395220 4 36 theme additional 677:686 arg1 steps 699:703 additional cumbersome steps 677:703 additional cumbersome steps 677:703 The removal of undesirable products, such as aggregation, depends primarily on purification, requiring additional cumbersome steps, which can lead to a lower product yield and longer timelines. 25395220 9 37 theme product 1599:1605 arg1 quality 1607:1613 product quality 1599:1613 product quality 1599:1613 These techniques have produced a similar improvement in product quality with a variety of other molecules, suggesting that this may be a general approach to enhance product quality from transient expression systems. 25395220 7 38 used used 1110:1113 arg2 approach 1094:1101 This approach 1089:1101 This approach 1089:1101 This approach can be used in combination with a temperature shift to hypothermic conditions during production to enhance the effect. 25395220 5 39 theme prone 912:916 arg1 molecules 902:910 secreted molecules 893:910 secreted molecules prone to aggregation 893:931 In this study, we show that reducing the level of transcription by transfecting at a lower gene dose improves the quality of secreted molecules prone to aggregation. 25395220 4 40 theme longer 750:755 arg1 timelines 757:765 longer timelines 750:765 longer timelines 750:765 The removal of undesirable products, such as aggregation, depends primarily on purification, requiring additional cumbersome steps, which can lead to a lower product yield and longer timelines. 25395220 8 41 theme aggregation 1267:1277 arg1 levels 1279:1284 aggregation levels 1267:1284 aggregation levels 1267:1284 The observed improvements not only minimized aggregation levels, but also generated products with overall superior quality, including more homogeneous signal peptide cleavage and N-linked glycosylation profiles. 25395220 8 42 theme superior 1328:1335 arg1 quality 1337:1343 overall superior quality 1320:1343 overall superior quality 1320:1343 The observed improvements not only minimized aggregation levels, but also generated products with overall superior quality, including more homogeneous signal peptide cleavage and N-linked glycosylation profiles. 25395220 0 43 theme expression 111:120 arg1 system 122:127 a transient expression system 99:127 a transient expression system 99:127 Uncovering methods for the prevention of protein aggregation and improvement of product quality in a transient expression system. 25395220 7 44 with combination 1118:1128 arg1 shift 1149:1153 a temperature shift 1135:1153 a temperature shift to hypothermic conditions during production 1135:1197 This approach can be used in combination with a temperature shift to hypothermic conditions during production to enhance the effect. 25395220 1 45 theme recombinant 200:210 arg1 proteins 212:219 recombinant proteins 200:219 recombinant proteins 200:219 Mammalian expression systems are used routinely for the production of recombinant proteins as therapeutic molecules as well as research tools. 25395220 9 46 theme expression 1630:1639 arg1 systems 1641:1647 transient expression systems 1620:1647 transient expression systems 1620:1647 These techniques have produced a similar improvement in product quality with a variety of other molecules, suggesting that this may be a general approach to enhance product quality from transient expression systems. 25395220 4 47 theme cumbersome 688:697 arg1 steps 699:703 additional cumbersome steps 677:703 additional cumbersome steps 677:703 The removal of undesirable products, such as aggregation, depends primarily on purification, requiring additional cumbersome steps, which can lead to a lower product yield and longer timelines. 25395220 8 48 theme glycosylation 1410:1422 arg1 profiles 1424:1431 N-linked glycosylation profiles 1401:1431 N-linked glycosylation profiles 1401:1431 The observed improvements not only minimized aggregation levels, but also generated products with overall superior quality, including more homogeneous signal peptide cleavage and N-linked glycosylation profiles. 25395220 5 49 theme gene 859:862 arg1 dose 864:867 a lower gene dose 851:867 a lower gene dose 851:867 In this study, we show that reducing the level of transcription by transfecting at a lower gene dose improves the quality of secreted molecules prone to aggregation. 25395220 1 50 theme proteins 212:219 arg1 production 186:195 the production 182:195 the production of recombinant proteins 182:219 Mammalian expression systems are used routinely for the production of recombinant proteins as therapeutic molecules as well as research tools. 25395220 3 51 theme transient 428:436 arg1 systems 449:455 transient expression systems 428:455 transient expression systems 428:455 While improvements to transient expression systems have focused mainly on the level of protein expression, the aspect of protein quality has received little attention. 25395220 5 52 theme lower 853:857 arg1 dose 864:867 a lower gene dose 851:867 a lower gene dose 851:867 In this study, we show that reducing the level of transcription by transfecting at a lower gene dose improves the quality of secreted molecules prone to aggregation. 25395220 6 53 contain containing 1069:1078 arg2 plasmid 1080:1086 plasmid 1080:1086 plasmid 1080:1086 For gene dosing to have this effect, it is critical for the carrier DNA to be an empty vector containing the same elements as the gene containing plasmid. 25395220 6 53 contain containing 1069:1078 arg1 gene 1064:1067 the gene 1060:1067 the gene containing plasmid 1060:1086 For gene dosing to have this effect, it is critical for the carrier DNA to be an empty vector containing the same elements as the gene containing plasmid. 25395220 6 54 theme carrier 994:1000 arg1 vector 1021:1026 an empty vector 1012:1026 an empty vector containing the same elements as the gene containing plasmid 1012:1086 For gene dosing to have this effect, it is critical for the carrier DNA to be an empty vector containing the same elements as the gene containing plasmid. 25395220 6 54 theme carrier 994:1000 arg1 DNA 1002:1004 the carrier DNA 990:1004 the carrier DNA 990:1004 For gene dosing to have this effect, it is critical for the carrier DNA to be an empty vector containing the same elements as the gene containing plasmid. 25395220 0 55 theme aggregation 49:59 arg1 improvement 65:75 improvement 65:75 improvement of product quality 65:94 Uncovering methods for the prevention of protein aggregation and improvement of product quality in a transient expression system. 25395220 0 55 theme aggregation 49:59 arg1 prevention 27:36 the prevention 23:36 the prevention of protein aggregation 23:59 Uncovering methods for the prevention of protein aggregation and improvement of product quality in a transient expression system. 25395220 8 56 theme signal 1373:1378 arg1 cleavage 1388:1395 more homogeneous signal peptide cleavage 1356:1395 more homogeneous signal peptide cleavage 1356:1395 The observed improvements not only minimized aggregation levels, but also generated products with overall superior quality, including more homogeneous signal peptide cleavage and N-linked glycosylation profiles. 25395220 8 57 theme overall 1320:1326 arg1 quality 1337:1343 overall superior quality 1320:1343 overall superior quality 1320:1343 The observed improvements not only minimized aggregation levels, but also generated products with overall superior quality, including more homogeneous signal peptide cleavage and N-linked glycosylation profiles. 25395220 3 58 theme expression 501:510 arg1 level 484:488 the level 480:488 the level of protein expression 480:510 While improvements to transient expression systems have focused mainly on the level of protein expression, the aspect of protein quality has received little attention. 25395220 0 59 theme protein 41:47 arg1 aggregation 49:59 protein aggregation 41:59 protein aggregation 41:59 Uncovering methods for the prevention of protein aggregation and improvement of product quality in a transient expression system. 25395220 8 60 theme homogeneous 1361:1371 arg1 cleavage 1388:1395 more homogeneous signal peptide cleavage 1356:1395 more homogeneous signal peptide cleavage 1356:1395 The observed improvements not only minimized aggregation levels, but also generated products with overall superior quality, including more homogeneous signal peptide cleavage and N-linked glycosylation profiles. 25395220 5 61 theme molecules 902:910 arg1 quality 882:888 the quality 878:888 the quality of secreted molecules prone to aggregation 878:931 In this study, we show that reducing the level of transcription by transfecting at a lower gene dose improves the quality of secreted molecules prone to aggregation. 25395220 9 62 from improvement 1475:1485 arg1 quality 1498:1504 product quality 1490:1504 product quality 1490:1504 These techniques have produced a similar improvement in product quality with a variety of other molecules, suggesting that this may be a general approach to enhance product quality from transient expression systems. 25395220 8 63 theme observed 1226:1233 arg1 improvements 1235:1246 The observed improvements 1222:1246 The observed improvements 1222:1246 The observed improvements not only minimized aggregation levels, but also generated products with overall superior quality, including more homogeneous signal peptide cleavage and N-linked glycosylation profiles. 25395220 2 64 theme due 342:344 arg1 years 336:340 recent years 329:340 recent years due to its rapid timeline and improvements in expression level 329:403 Transient expression has become increasingly popular in recent years due to its rapid timeline and improvements in expression level. 25395220 1 65 theme therapeutic 224:234 arg1 systems 151:157 Mammalian expression systems 130:157 Mammalian expression systems 130:157 Mammalian expression systems are used routinely for the production of recombinant proteins as therapeutic molecules as well as research tools. 25395220 1 65 theme therapeutic 224:234 arg1 molecules 236:244 therapeutic molecules 224:244 therapeutic molecules as well as research tools 224:270 Mammalian expression systems are used routinely for the production of recombinant proteins as therapeutic molecules as well as research tools. 25395220 8 66 theme peptide 1380:1386 arg1 cleavage 1388:1395 more homogeneous signal peptide cleavage 1356:1395 more homogeneous signal peptide cleavage 1356:1395 The observed improvements not only minimized aggregation levels, but also generated products with overall superior quality, including more homogeneous signal peptide cleavage and N-linked glycosylation profiles. 25395220 1 67 theme Mammalian 130:138 arg1 systems 151:157 Mammalian expression systems 130:157 Mammalian expression systems 130:157 Mammalian expression systems are used routinely for the production of recombinant proteins as therapeutic molecules as well as research tools. 25395220 1 67 theme Mammalian 130:138 arg1 tools 266:270 research tools 257:270 therapeutic molecules as well as research tools 224:270 Mammalian expression systems are used routinely for the production of recombinant proteins as therapeutic molecules as well as research tools. 25395220 1 67 theme Mammalian 130:138 arg1 molecules 236:244 therapeutic molecules 224:244 therapeutic molecules as well as research tools 224:270 Mammalian expression systems are used routinely for the production of recombinant proteins as therapeutic molecules as well as research tools. 25395220 4 68 theme lower 726:730 arg1 yield 740:744 a lower product yield 724:744 a lower product yield 724:744 The removal of undesirable products, such as aggregation, depends primarily on purification, requiring additional cumbersome steps, which can lead to a lower product yield and longer timelines. 25395220 8 69 theme N-linked 1401:1408 arg1 profiles 1424:1431 N-linked glycosylation profiles 1401:1431 N-linked glycosylation profiles 1401:1431 The observed improvements not only minimized aggregation levels, but also generated products with overall superior quality, including more homogeneous signal peptide cleavage and N-linked glycosylation profiles. 25395220 1 70 theme expression 140:149 arg1 systems 151:157 Mammalian expression systems 130:157 Mammalian expression systems 130:157 Mammalian expression systems are used routinely for the production of recombinant proteins as therapeutic molecules as well as research tools. 25395220 1 70 theme expression 140:149 arg1 tools 266:270 research tools 257:270 therapeutic molecules as well as research tools 224:270 Mammalian expression systems are used routinely for the production of recombinant proteins as therapeutic molecules as well as research tools. 25395220 1 70 theme expression 140:149 arg1 molecules 236:244 therapeutic molecules 224:244 therapeutic molecules as well as research tools 224:270 Mammalian expression systems are used routinely for the production of recombinant proteins as therapeutic molecules as well as research tools. 25395220 3 71 theme protein 527:533 arg1 quality 535:541 protein quality 527:541 protein quality 527:541 While improvements to transient expression systems have focused mainly on the level of protein expression, the aspect of protein quality has received little attention. 25395220 2 72 from popular 318:324 arg1 years 336:340 recent years 329:340 recent years due to its rapid timeline and improvements in expression level 329:403 Transient expression has become increasingly popular in recent years due to its rapid timeline and improvements in expression level. 24668018 0 0 theme Pichia 65:70 arg1 anomala 72:78 Pichia anomala 65:78 Pichia anomala 65:78 Optimization of heterologous expression of the phytase (PPHY) of Pichia anomala in P. pastoris and its applicability in fractionating allergenic glycinin from soy protein. 24668018 1 1 theme acidstability 261:273 arg1 insensitivity 315:327 protease insensitivity 306:327 protease insensitivity 306:327 The phytase (PPHY) of Pichia anomala has the requisite properties of thermostability and acidstability, broad substrate spectrum, and protease insensitivity, which make it a suitable candidate as a feed and food additive. 24668018 1 1 theme acidstability 261:273 arg1 spectrum 292:299 broad substrate spectrum 276:299 broad substrate spectrum 276:299 The phytase (PPHY) of Pichia anomala has the requisite properties of thermostability and acidstability, broad substrate spectrum, and protease insensitivity, which make it a suitable candidate as a feed and food additive. 24668018 1 1 theme acidstability 261:273 arg1 properties 227:236 the requisite properties 213:236 the requisite properties of thermostability and acidstability 213:273 The phytase (PPHY) of Pichia anomala has the requisite properties of thermostability and acidstability, broad substrate spectrum, and protease insensitivity, which make it a suitable candidate as a feed and food additive. 24668018 6 2 dep characteristics 928:942 arg1 m 946:946 m 946:946 m 946:946 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) of rPPHY are 0.2 ± 0.03 mM, 78.2 ± 1.43 nmol mg(-1) s(-1), 65,655 ± 10.92 s(-1), and 328.3 ± 3.12 μM(-1) s(-1), respectively. 24668018 6 2 dep characteristics 928:942 arg1 m 979:979 m 979:979 m 979:979 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) of rPPHY are 0.2 ± 0.03 mM, 78.2 ± 1.43 nmol mg(-1) s(-1), 65,655 ± 10.92 s(-1), and 328.3 ± 3.12 μM(-1) s(-1), respectively. 24668018 6 2 dep characteristics 928:942 arg1 K 958:958 K 958:958 K(cat) 958:963 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) of rPPHY are 0.2 ± 0.03 mM, 78.2 ± 1.43 nmol mg(-1) s(-1), 65,655 ± 10.92 s(-1), and 328.3 ± 3.12 μM(-1) s(-1), respectively. 24668018 6 2 dep characteristics 928:942 arg1 cat 960:962 cat 960:962 cat 960:962 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) of rPPHY are 0.2 ± 0.03 mM, 78.2 ± 1.43 nmol mg(-1) s(-1), 65,655 ± 10.92 s(-1), and 328.3 ± 3.12 μM(-1) s(-1), respectively. 24668018 6 2 dep characteristics 928:942 arg1 characteristics 928:942 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) 916:980 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) of rPPHY 916:989 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) of rPPHY are 0.2 ± 0.03 mM, 78.2 ± 1.43 nmol mg(-1) s(-1), 65,655 ± 10.92 s(-1), and 328.3 ± 3.12 μM(-1) s(-1), respectively. 24668018 6 2 dep characteristics 928:942 arg1 V 950:950 V 950:950 V(max) 950:955 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) of rPPHY are 0.2 ± 0.03 mM, 78.2 ± 1.43 nmol mg(-1) s(-1), 65,655 ± 10.92 s(-1), and 328.3 ± 3.12 μM(-1) s(-1), respectively. 24668018 6 2 dep characteristics 928:942 arg1 K 944:944 K 944:944 K(m) 944:947 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) of rPPHY are 0.2 ± 0.03 mM, 78.2 ± 1.43 nmol mg(-1) s(-1), 65,655 ± 10.92 s(-1), and 328.3 ± 3.12 μM(-1) s(-1), respectively. 24668018 6 2 dep characteristics 928:942 arg1 /K 976:977 K(cat)/K 970:977 K(cat)/K(m) 970:980 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) of rPPHY are 0.2 ± 0.03 mM, 78.2 ± 1.43 nmol mg(-1) s(-1), 65,655 ± 10.92 s(-1), and 328.3 ± 3.12 μM(-1) s(-1), respectively. 24668018 6 2 dep characteristics 928:942 arg1 max 952:954 max 952:954 max 952:954 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) of rPPHY are 0.2 ± 0.03 mM, 78.2 ± 1.43 nmol mg(-1) s(-1), 65,655 ± 10.92 s(-1), and 328.3 ± 3.12 μM(-1) s(-1), respectively. 24668018 5 3 theme temperature 828:838 arg1 °C 870:871 60 °C 867:871 60 °C 867:871 The temperature and pH optima of rPPHY are 60 °C and 4.0, similar to the endogenous enzyme. 24668018 5 3 theme temperature 828:838 arg1 optima 847:852 The temperature and pH optima 824:852 optima 847:852 The temperature and pH optima of rPPHY are 60 °C and 4.0, similar to the endogenous enzyme. 24668018 10 4 theme allergenic 1445:1454 arg1 glycinin 1464:1471 allergenic protein glycinin 1445:1471 allergenic protein glycinin from soya protein besides dephytinization 1445:1513 The enzyme has been found useful in fractionating allergenic protein glycinin from soya protein besides dephytinization. 24668018 7 5 theme endogenous 1206:1215 arg1 yeast 1217:1221 the endogenous yeast 1202:1221 the endogenous yeast 1202:1221 The optimization of medium components led to a 21.8-fold improvement in rPPHY production over the endogenous yeast. 24668018 1 6 theme protease 306:313 arg1 insensitivity 315:327 protease insensitivity 306:327 protease insensitivity 306:327 The phytase (PPHY) of Pichia anomala has the requisite properties of thermostability and acidstability, broad substrate spectrum, and protease insensitivity, which make it a suitable candidate as a feed and food additive. 24668018 3 7 theme P. 624:625 arg1 pastoris 627:634 the recombinant P. pastoris 608:634 the recombinant P. pastoris 608:634 Three copies of PPHY have been detected integrated into the chromosomal DNA of the recombinant P. pastoris. 24668018 0 8 theme soy 159:161 arg1 protein 163:169 soy protein 159:169 soy protein 159:169 Optimization of heterologous expression of the phytase (PPHY) of Pichia anomala in P. pastoris and its applicability in fractionating allergenic glycinin from soy protein. 24668018 2 9 theme anomala 439:445 arg1 DNA 455:457 anomala genomic DNA 439:457 P. anomala genomic DNA 436:457 The 1,389-bp PPHY gene was amplified from P. anomala genomic DNA, cloned in pPICZαA, and expressed extracellularly in P. pastoris X33. 24668018 10 10 theme soya 1478:1481 arg1 protein 1483:1489 soya protein 1478:1489 soya protein 1478:1489 The enzyme has been found useful in fractionating allergenic protein glycinin from soya protein besides dephytinization. 24668018 1 11 theme requisite 217:225 arg1 properties 227:236 the requisite properties 213:236 the requisite properties of thermostability and acidstability 213:273 The phytase (PPHY) of Pichia anomala has the requisite properties of thermostability and acidstability, broad substrate spectrum, and protease insensitivity, which make it a suitable candidate as a feed and food additive. 24668018 7 12 from improvement 1165:1175 arg1 production 1186:1195 rPPHY production 1180:1195 rPPHY production 1180:1195 The optimization of medium components led to a 21.8-fold improvement in rPPHY production over the endogenous yeast. 24668018 0 13 from Optimization 0:11 arg1 pastoris 86:93 P. pastoris 83:93 P. pastoris 83:93 Optimization of heterologous expression of the phytase (PPHY) of Pichia anomala in P. pastoris and its applicability in fractionating allergenic glycinin from soy protein. 24668018 4 14 theme rPPHY 711:715 arg1 electrophoresis 683:697 electrophoresis 683:697 electrophoresis of the pure rPPHY 683:715 The size exclusion chromatography followed by electrophoresis of the pure rPPHY confirmed that this is a homohexameric glycoprotein of ~420 kDa with a 24.3 % portion as N-linked glycans. 24668018 1 15 dep feed 370:373 arg1 a 368:368 a 368:368 a 368:368 The phytase (PPHY) of Pichia anomala has the requisite properties of thermostability and acidstability, broad substrate spectrum, and protease insensitivity, which make it a suitable candidate as a feed and food additive. 24668018 0 16 theme anomala 72:78 arg1 PPHY 56:59 PPHY 56:59 PPHY 56:59 Optimization of heterologous expression of the phytase (PPHY) of Pichia anomala in P. pastoris and its applicability in fractionating allergenic glycinin from soy protein. 24668018 0 16 theme anomala 72:78 arg1 phytase 47:53 the phytase 43:53 the phytase (PPHY) of Pichia anomala 43:78 Optimization of heterologous expression of the phytase (PPHY) of Pichia anomala in P. pastoris and its applicability in fractionating allergenic glycinin from soy protein. 24668018 4 17 theme N-linked 806:813 arg1 glycans 815:821 N-linked glycans 806:821 N-linked glycans 806:821 The size exclusion chromatography followed by electrophoresis of the pure rPPHY confirmed that this is a homohexameric glycoprotein of ~420 kDa with a 24.3 % portion as N-linked glycans. 24668018 4 18 theme pure 706:709 arg1 rPPHY 711:715 the pure rPPHY 702:715 the pure rPPHY 702:715 The size exclusion chromatography followed by electrophoresis of the pure rPPHY confirmed that this is a homohexameric glycoprotein of ~420 kDa with a 24.3 % portion as N-linked glycans. 24668018 5 19 theme pH 844:845 arg1 °C 870:871 60 °C 867:871 60 °C 867:871 The temperature and pH optima of rPPHY are 60 °C and 4.0, similar to the endogenous enzyme. 24668018 5 19 theme pH 844:845 arg1 optima 847:852 The temperature and pH optima 824:852 optima 847:852 The temperature and pH optima of rPPHY are 60 °C and 4.0, similar to the endogenous enzyme. 24668018 6 20 theme mg 1027:1028 arg1 -1 1036:1037 -1 1036:1037 -1 1036:1037 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) of rPPHY are 0.2 ± 0.03 mM, 78.2 ± 1.43 nmol mg(-1) s(-1), 65,655 ± 10.92 s(-1), and 328.3 ± 3.12 μM(-1) s(-1), respectively. 24668018 6 20 theme mg 1027:1028 arg1 s 1034:1034 78.2 ± 1.43 nmol mg(-1) s 1010:1034 78.2 ± 1.43 nmol mg(-1) s(-1) 1010:1038 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) of rPPHY are 0.2 ± 0.03 mM, 78.2 ± 1.43 nmol mg(-1) s(-1), 65,655 ± 10.92 s(-1), and 328.3 ± 3.12 μM(-1) s(-1), respectively. 24668018 5 21 theme similar 882:888 arg1 °C 870:871 60 °C 867:871 60 °C 867:871 The temperature and pH optima of rPPHY are 60 °C and 4.0, similar to the endogenous enzyme. 24668018 5 21 theme similar 882:888 arg1 optima 847:852 The temperature and pH optima 824:852 optima 847:852 The temperature and pH optima of rPPHY are 60 °C and 4.0, similar to the endogenous enzyme. 24668018 6 22 theme ± 1015:1015 arg1 -1 1036:1037 -1 1036:1037 -1 1036:1037 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) of rPPHY are 0.2 ± 0.03 mM, 78.2 ± 1.43 nmol mg(-1) s(-1), 65,655 ± 10.92 s(-1), and 328.3 ± 3.12 μM(-1) s(-1), respectively. 24668018 6 22 theme ± 1015:1015 arg1 s 1034:1034 78.2 ± 1.43 nmol mg(-1) s 1010:1034 78.2 ± 1.43 nmol mg(-1) s(-1) 1010:1038 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) of rPPHY are 0.2 ± 0.03 mM, 78.2 ± 1.43 nmol mg(-1) s(-1), 65,655 ± 10.92 s(-1), and 328.3 ± 3.12 μM(-1) s(-1), respectively. 24668018 6 23 theme μM 1080:1081 arg1 -1 1089:1090 -1 1089:1090 -1 1089:1090 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) of rPPHY are 0.2 ± 0.03 mM, 78.2 ± 1.43 nmol mg(-1) s(-1), 65,655 ± 10.92 s(-1), and 328.3 ± 3.12 μM(-1) s(-1), respectively. 24668018 6 23 theme μM 1080:1081 arg1 s 1087:1087 328.3 ± 3.12 μM(-1) s 1067:1087 328.3 ± 3.12 μM(-1) s(-1) 1067:1091 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) of rPPHY are 0.2 ± 0.03 mM, 78.2 ± 1.43 nmol mg(-1) s(-1), 65,655 ± 10.92 s(-1), and 328.3 ± 3.12 μM(-1) s(-1), respectively. 24668018 6 24 theme nmol 1022:1025 arg1 -1 1036:1037 -1 1036:1037 -1 1036:1037 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) of rPPHY are 0.2 ± 0.03 mM, 78.2 ± 1.43 nmol mg(-1) s(-1), 65,655 ± 10.92 s(-1), and 328.3 ± 3.12 μM(-1) s(-1), respectively. 24668018 6 24 theme nmol 1022:1025 arg1 s 1034:1034 78.2 ± 1.43 nmol mg(-1) s 1010:1034 78.2 ± 1.43 nmol mg(-1) s(-1) 1010:1038 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) of rPPHY are 0.2 ± 0.03 mM, 78.2 ± 1.43 nmol mg(-1) s(-1), 65,655 ± 10.92 s(-1), and 328.3 ± 3.12 μM(-1) s(-1), respectively. 24668018 1 25 theme Pichia 194:199 arg1 anomala 201:207 Pichia anomala 194:207 Pichia anomala 194:207 The phytase (PPHY) of Pichia anomala has the requisite properties of thermostability and acidstability, broad substrate spectrum, and protease insensitivity, which make it a suitable candidate as a feed and food additive. 24668018 2 26 theme PPHY 407:410 arg1 gene 412:415 The 1,389-bp PPHY gene 394:415 The 1,389-bp PPHY gene 394:415 The 1,389-bp PPHY gene was amplified from P. anomala genomic DNA, cloned in pPICZαA, and expressed extracellularly in P. pastoris X33. 24668018 4 27 link N-linked 806:813 arg1 glycans 815:821 N-linked glycans 806:821 N-linked glycans 806:821 The size exclusion chromatography followed by electrophoresis of the pure rPPHY confirmed that this is a homohexameric glycoprotein of ~420 kDa with a 24.3 % portion as N-linked glycans. 24668018 4 28 theme % 793:793 arg1 portion 795:801 a 24.3 % portion 786:801 a 24.3 % portion as N-linked glycans 786:821 The size exclusion chromatography followed by electrophoresis of the pure rPPHY confirmed that this is a homohexameric glycoprotein of ~420 kDa with a 24.3 % portion as N-linked glycans. 24668018 10 29 from protein 1483:1489 arg1 glycinin 1464:1471 allergenic protein glycinin 1445:1471 allergenic protein glycinin from soya protein besides dephytinization 1445:1513 The enzyme has been found useful in fractionating allergenic protein glycinin from soya protein besides dephytinization. 24668018 9 30 theme total 1355:1359 arg1 protein 1370:1376 the total secreted protein 1351:1376 the total secreted protein into the medium 1351:1392 The rPPHY accounts for 57.1 % of the total secreted protein into the medium. 24668018 8 31 theme shake 1252:1256 arg1 flasks 1258:1263 shake flasks 1252:1263 shake flasks 1252:1263 The rPPHY titer attained in shake flasks could also be sustained in the laboratory fermenter. 24668018 3 32 theme pastoris 627:634 arg1 DNA 601:603 the chromosomal DNA 585:603 the chromosomal DNA of the recombinant P. pastoris 585:634 Three copies of PPHY have been detected integrated into the chromosomal DNA of the recombinant P. pastoris. 24668018 2 33 theme 1,389-bp 398:405 arg1 gene 412:415 The 1,389-bp PPHY gene 394:415 The 1,389-bp PPHY gene 394:415 The 1,389-bp PPHY gene was amplified from P. anomala genomic DNA, cloned in pPICZαA, and expressed extracellularly in P. pastoris X33. 24668018 1 34 theme thermostability 241:255 arg1 insensitivity 315:327 protease insensitivity 306:327 protease insensitivity 306:327 The phytase (PPHY) of Pichia anomala has the requisite properties of thermostability and acidstability, broad substrate spectrum, and protease insensitivity, which make it a suitable candidate as a feed and food additive. 24668018 1 34 theme thermostability 241:255 arg1 spectrum 292:299 broad substrate spectrum 276:299 broad substrate spectrum 276:299 The phytase (PPHY) of Pichia anomala has the requisite properties of thermostability and acidstability, broad substrate spectrum, and protease insensitivity, which make it a suitable candidate as a feed and food additive. 24668018 1 34 theme thermostability 241:255 arg1 properties 227:236 the requisite properties 213:236 the requisite properties of thermostability and acidstability 213:273 The phytase (PPHY) of Pichia anomala has the requisite properties of thermostability and acidstability, broad substrate spectrum, and protease insensitivity, which make it a suitable candidate as a feed and food additive. 24668018 4 35 theme 24.3 788:791 arg1 % 793:793 % 793:793 % 793:793 The size exclusion chromatography followed by electrophoresis of the pure rPPHY confirmed that this is a homohexameric glycoprotein of ~420 kDa with a 24.3 % portion as N-linked glycans. 24668018 7 36 theme components 1135:1144 arg1 optimization 1112:1123 The optimization 1108:1123 The optimization of medium components 1108:1144 The optimization of medium components led to a 21.8-fold improvement in rPPHY production over the endogenous yeast. 24668018 3 37 theme chromosomal 589:599 arg1 DNA 601:603 the chromosomal DNA 585:603 the chromosomal DNA of the recombinant P. pastoris 585:634 Three copies of PPHY have been detected integrated into the chromosomal DNA of the recombinant P. pastoris. 24668018 0 38 theme expression 29:38 arg1 Optimization 0:11 Optimization 0:11 Optimization of heterologous expression of the phytase (PPHY) of Pichia anomala in P. pastoris and its applicability in fractionating allergenic glycinin from soy protein. 0:170 Optimization of heterologous expression of the phytase (PPHY) of Pichia anomala in P. pastoris and its applicability in fractionating allergenic glycinin from soy protein. 24668018 4 39 theme homohexameric 742:754 arg1 this 732:735 this 732:735 this 732:735 The size exclusion chromatography followed by electrophoresis of the pure rPPHY confirmed that this is a homohexameric glycoprotein of ~420 kDa with a 24.3 % portion as N-linked glycans. 24668018 4 39 theme homohexameric 742:754 arg1 glycoprotein 756:767 a homohexameric glycoprotein 740:767 a homohexameric glycoprotein of ~420 kDa with a 24.3 % portion as N-linked glycans 740:821 The size exclusion chromatography followed by electrophoresis of the pure rPPHY confirmed that this is a homohexameric glycoprotein of ~420 kDa with a 24.3 % portion as N-linked glycans. 24668018 6 40 theme cat 972:974 arg1 m 979:979 m 979:979 m 979:979 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) of rPPHY are 0.2 ± 0.03 mM, 78.2 ± 1.43 nmol mg(-1) s(-1), 65,655 ± 10.92 s(-1), and 328.3 ± 3.12 μM(-1) s(-1), respectively. 24668018 6 40 theme cat 972:974 arg1 /K 976:977 K(cat)/K 970:977 K(cat)/K(m) 970:980 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) of rPPHY are 0.2 ± 0.03 mM, 78.2 ± 1.43 nmol mg(-1) s(-1), 65,655 ± 10.92 s(-1), and 328.3 ± 3.12 μM(-1) s(-1), respectively. 24668018 6 40 theme cat 972:974 arg1 characteristics 928:942 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) 916:980 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) of rPPHY 916:989 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) of rPPHY are 0.2 ± 0.03 mM, 78.2 ± 1.43 nmol mg(-1) s(-1), 65,655 ± 10.92 s(-1), and 328.3 ± 3.12 μM(-1) s(-1), respectively. 24668018 10 41 theme protein 1456:1462 arg1 glycinin 1464:1471 allergenic protein glycinin 1445:1471 allergenic protein glycinin from soya protein besides dephytinization 1445:1513 The enzyme has been found useful in fractionating allergenic protein glycinin from soya protein besides dephytinization. 24668018 0 42 theme heterologous 16:27 arg1 expression 29:38 heterologous expression 16:38 heterologous expression of the phytase (PPHY) of Pichia anomala in P. pastoris 16:93 Optimization of heterologous expression of the phytase (PPHY) of Pichia anomala in P. pastoris and its applicability in fractionating allergenic glycinin from soy protein. 24668018 0 43 from protein 163:169 arg1 glycinin 145:152 allergenic glycinin 134:152 allergenic glycinin from soy protein 134:169 Optimization of heterologous expression of the phytase (PPHY) of Pichia anomala in P. pastoris and its applicability in fractionating allergenic glycinin from soy protein. 24668018 6 44 theme 10.92 1050:1054 arg1 -1 1058:1059 -1 1058:1059 -1 1058:1059 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) of rPPHY are 0.2 ± 0.03 mM, 78.2 ± 1.43 nmol mg(-1) s(-1), 65,655 ± 10.92 s(-1), and 328.3 ± 3.12 μM(-1) s(-1), respectively. 24668018 6 44 theme 10.92 1050:1054 arg1 s 1056:1056 65,655 ± 10.92 s 1041:1056 65,655 ± 10.92 s(-1) 1041:1060 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) of rPPHY are 0.2 ± 0.03 mM, 78.2 ± 1.43 nmol mg(-1) s(-1), 65,655 ± 10.92 s(-1), and 328.3 ± 3.12 μM(-1) s(-1), respectively. 24668018 1 45 theme suitable 346:353 arg1 candidate 355:363 a suitable candidate 344:363 a suitable candidate as a feed and food additive 344:391 The phytase (PPHY) of Pichia anomala has the requisite properties of thermostability and acidstability, broad substrate spectrum, and protease insensitivity, which make it a suitable candidate as a feed and food additive. 24668018 9 46 theme secreted 1361:1368 arg1 protein 1370:1376 the total secreted protein 1351:1376 the total secreted protein into the medium 1351:1392 The rPPHY accounts for 57.1 % of the total secreted protein into the medium. 24668018 6 47 theme ± 1048:1048 arg1 -1 1058:1059 -1 1058:1059 -1 1058:1059 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) of rPPHY are 0.2 ± 0.03 mM, 78.2 ± 1.43 nmol mg(-1) s(-1), 65,655 ± 10.92 s(-1), and 328.3 ± 3.12 μM(-1) s(-1), respectively. 24668018 6 47 theme ± 1048:1048 arg1 s 1056:1056 65,655 ± 10.92 s 1041:1056 65,655 ± 10.92 s(-1) 1041:1060 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) of rPPHY are 0.2 ± 0.03 mM, 78.2 ± 1.43 nmol mg(-1) s(-1), 65,655 ± 10.92 s(-1), and 328.3 ± 3.12 μM(-1) s(-1), respectively. 24668018 1 48 dep has 209:211 arg1 make 336:339 make 336:339 make it a suitable candidate as a feed and food additive 336:391 The phytase (PPHY) of Pichia anomala has the requisite properties of thermostability and acidstability, broad substrate spectrum, and protease insensitivity, which make it a suitable candidate as a feed and food additive. 24668018 1 49 contain has 209:211 arg2 spectrum 292:299 broad substrate spectrum 276:299 broad substrate spectrum 276:299 The phytase (PPHY) of Pichia anomala has the requisite properties of thermostability and acidstability, broad substrate spectrum, and protease insensitivity, which make it a suitable candidate as a feed and food additive. 24668018 1 49 contain has 209:211 arg1 PPHY 185:188 PPHY 185:188 PPHY 185:188 The phytase (PPHY) of Pichia anomala has the requisite properties of thermostability and acidstability, broad substrate spectrum, and protease insensitivity, which make it a suitable candidate as a feed and food additive. 24668018 1 49 contain has 209:211 arg2 properties 227:236 the requisite properties 213:236 the requisite properties of thermostability and acidstability 213:273 The phytase (PPHY) of Pichia anomala has the requisite properties of thermostability and acidstability, broad substrate spectrum, and protease insensitivity, which make it a suitable candidate as a feed and food additive. 24668018 1 49 contain has 209:211 arg1 phytase 176:182 The phytase 172:182 The phytase (PPHY) of Pichia anomala 172:207 The phytase (PPHY) of Pichia anomala has the requisite properties of thermostability and acidstability, broad substrate spectrum, and protease insensitivity, which make it a suitable candidate as a feed and food additive. 24668018 1 49 contain has 209:211 arg2 insensitivity 315:327 protease insensitivity 306:327 protease insensitivity 306:327 The phytase (PPHY) of Pichia anomala has the requisite properties of thermostability and acidstability, broad substrate spectrum, and protease insensitivity, which make it a suitable candidate as a feed and food additive. 24668018 1 50 theme broad 276:280 arg1 spectrum 292:299 broad substrate spectrum 276:299 broad substrate spectrum 276:299 The phytase (PPHY) of Pichia anomala has the requisite properties of thermostability and acidstability, broad substrate spectrum, and protease insensitivity, which make it a suitable candidate as a feed and food additive. 24668018 0 51 theme applicability 103:115 arg1 Optimization 0:11 Optimization 0:11 Optimization of heterologous expression of the phytase (PPHY) of Pichia anomala in P. pastoris and its applicability in fractionating allergenic glycinin from soy protein. 0:170 Optimization of heterologous expression of the phytase (PPHY) of Pichia anomala in P. pastoris and its applicability in fractionating allergenic glycinin from soy protein. 24668018 6 52 theme kinetic 920:926 arg1 K 958:958 K 958:958 K(cat) 958:963 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) of rPPHY are 0.2 ± 0.03 mM, 78.2 ± 1.43 nmol mg(-1) s(-1), 65,655 ± 10.92 s(-1), and 328.3 ± 3.12 μM(-1) s(-1), respectively. 24668018 6 52 theme kinetic 920:926 arg1 mM 1006:1007 0.2 ± 0.03 mM 995:1007 0.2 ± 0.03 mM 995:1007 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) of rPPHY are 0.2 ± 0.03 mM, 78.2 ± 1.43 nmol mg(-1) s(-1), 65,655 ± 10.92 s(-1), and 328.3 ± 3.12 μM(-1) s(-1), respectively. 24668018 6 52 theme kinetic 920:926 arg1 characteristics 928:942 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) 916:980 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) of rPPHY 916:989 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) of rPPHY are 0.2 ± 0.03 mM, 78.2 ± 1.43 nmol mg(-1) s(-1), 65,655 ± 10.92 s(-1), and 328.3 ± 3.12 μM(-1) s(-1), respectively. 24668018 6 52 theme kinetic 920:926 arg1 V 950:950 V 950:950 V(max) 950:955 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) of rPPHY are 0.2 ± 0.03 mM, 78.2 ± 1.43 nmol mg(-1) s(-1), 65,655 ± 10.92 s(-1), and 328.3 ± 3.12 μM(-1) s(-1), respectively. 24668018 6 52 theme kinetic 920:926 arg1 K 944:944 K 944:944 K(m) 944:947 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) of rPPHY are 0.2 ± 0.03 mM, 78.2 ± 1.43 nmol mg(-1) s(-1), 65,655 ± 10.92 s(-1), and 328.3 ± 3.12 μM(-1) s(-1), respectively. 24668018 6 52 theme kinetic 920:926 arg1 /K 976:977 K(cat)/K 970:977 K(cat)/K(m) 970:980 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) of rPPHY are 0.2 ± 0.03 mM, 78.2 ± 1.43 nmol mg(-1) s(-1), 65,655 ± 10.92 s(-1), and 328.3 ± 3.12 μM(-1) s(-1), respectively. 24668018 3 53 dep detected 560:567 arg1 integrated 569:578 integrated 569:578 integrated into the chromosomal DNA of the recombinant P. pastoris 569:634 Three copies of PPHY have been detected integrated into the chromosomal DNA of the recombinant P. pastoris. 24668018 1 54 theme substrate 282:290 arg1 spectrum 292:299 broad substrate spectrum 276:299 broad substrate spectrum 276:299 The phytase (PPHY) of Pichia anomala has the requisite properties of thermostability and acidstability, broad substrate spectrum, and protease insensitivity, which make it a suitable candidate as a feed and food additive. 24668018 0 55 theme allergenic 134:143 arg1 glycinin 145:152 allergenic glycinin 134:152 allergenic glycinin from soy protein 134:169 Optimization of heterologous expression of the phytase (PPHY) of Pichia anomala in P. pastoris and its applicability in fractionating allergenic glycinin from soy protein. 24668018 6 56 theme ± 1073:1073 arg1 -1 1089:1090 -1 1089:1090 -1 1089:1090 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) of rPPHY are 0.2 ± 0.03 mM, 78.2 ± 1.43 nmol mg(-1) s(-1), 65,655 ± 10.92 s(-1), and 328.3 ± 3.12 μM(-1) s(-1), respectively. 24668018 6 56 theme ± 1073:1073 arg1 s 1087:1087 328.3 ± 3.12 μM(-1) s 1067:1087 328.3 ± 3.12 μM(-1) s(-1) 1067:1091 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) of rPPHY are 0.2 ± 0.03 mM, 78.2 ± 1.43 nmol mg(-1) s(-1), 65,655 ± 10.92 s(-1), and 328.3 ± 3.12 μM(-1) s(-1), respectively. 24668018 4 57 theme kDa 777:779 arg1 this 732:735 this 732:735 this 732:735 The size exclusion chromatography followed by electrophoresis of the pure rPPHY confirmed that this is a homohexameric glycoprotein of ~420 kDa with a 24.3 % portion as N-linked glycans. 24668018 4 57 theme kDa 777:779 arg1 glycoprotein 756:767 a homohexameric glycoprotein 740:767 a homohexameric glycoprotein of ~420 kDa with a 24.3 % portion as N-linked glycans 740:821 The size exclusion chromatography followed by electrophoresis of the pure rPPHY confirmed that this is a homohexameric glycoprotein of ~420 kDa with a 24.3 % portion as N-linked glycans. 24668018 2 58 dep DNA 455:457 arg1 P. 436:437 P. anomala genomic DNA 436:457 P. anomala genomic DNA 436:457 The 1,389-bp PPHY gene was amplified from P. anomala genomic DNA, cloned in pPICZαA, and expressed extracellularly in P. pastoris X33. 24668018 4 59 theme exclusion 646:654 arg1 chromatography 656:669 The size exclusion chromatography 637:669 The size exclusion chromatography followed by electrophoresis of the pure rPPHY 637:715 The size exclusion chromatography followed by electrophoresis of the pure rPPHY confirmed that this is a homohexameric glycoprotein of ~420 kDa with a 24.3 % portion as N-linked glycans. 24668018 0 60 theme phytase 47:53 arg1 applicability 103:115 its applicability 99:115 its applicability 99:115 Optimization of heterologous expression of the phytase (PPHY) of Pichia anomala in P. pastoris and its applicability in fractionating allergenic glycinin from soy protein. 24668018 0 60 theme phytase 47:53 arg1 expression 29:38 heterologous expression 16:38 heterologous expression of the phytase (PPHY) of Pichia anomala in P. pastoris 16:93 Optimization of heterologous expression of the phytase (PPHY) of Pichia anomala in P. pastoris and its applicability in fractionating allergenic glycinin from soy protein. 24668018 7 61 theme medium 1128:1133 arg1 components 1135:1144 medium components 1128:1144 medium components 1128:1144 The optimization of medium components led to a 21.8-fold improvement in rPPHY production over the endogenous yeast. 24668018 0 62 from pastoris 86:93 arg1 Optimization 0:11 Optimization 0:11 Optimization of heterologous expression of the phytase (PPHY) of Pichia anomala in P. pastoris and its applicability in fractionating allergenic glycinin from soy protein. 0:170 Optimization of heterologous expression of the phytase (PPHY) of Pichia anomala in P. pastoris and its applicability in fractionating allergenic glycinin from soy protein. 24668018 7 63 theme 21.8-fold 1155:1163 arg1 improvement 1165:1175 a 21.8-fold improvement 1153:1175 a 21.8-fold improvement in rPPHY production over the endogenous yeast 1153:1221 The optimization of medium components led to a 21.8-fold improvement in rPPHY production over the endogenous yeast. 24668018 4 64 theme size 641:644 arg1 chromatography 656:669 The size exclusion chromatography 637:669 The size exclusion chromatography followed by electrophoresis of the pure rPPHY 637:715 The size exclusion chromatography followed by electrophoresis of the pure rPPHY confirmed that this is a homohexameric glycoprotein of ~420 kDa with a 24.3 % portion as N-linked glycans. 24668018 8 65 theme rPPHY 1228:1232 arg1 titer 1234:1238 The rPPHY titer 1224:1238 The rPPHY titer attained in shake flasks 1224:1263 The rPPHY titer attained in shake flasks could also be sustained in the laboratory fermenter. 24668018 2 66 theme P. 512:513 arg1 pastoris 515:522 P. pastoris X33 512:526 P. pastoris X33 512:526 The 1,389-bp PPHY gene was amplified from P. anomala genomic DNA, cloned in pPICZαA, and expressed extracellularly in P. pastoris X33. 24668018 3 67 theme recombinant 612:622 arg1 pastoris 627:634 the recombinant P. pastoris 608:634 the recombinant P. pastoris 608:634 Three copies of PPHY have been detected integrated into the chromosomal DNA of the recombinant P. pastoris. 24668018 6 68 theme ± 999:999 arg1 mM 1006:1007 0.2 ± 0.03 mM 995:1007 0.2 ± 0.03 mM 995:1007 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) of rPPHY are 0.2 ± 0.03 mM, 78.2 ± 1.43 nmol mg(-1) s(-1), 65,655 ± 10.92 s(-1), and 328.3 ± 3.12 μM(-1) s(-1), respectively. 24668018 6 68 theme ± 999:999 arg1 characteristics 928:942 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) 916:980 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) of rPPHY 916:989 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) of rPPHY are 0.2 ± 0.03 mM, 78.2 ± 1.43 nmol mg(-1) s(-1), 65,655 ± 10.92 s(-1), and 328.3 ± 3.12 μM(-1) s(-1), respectively. 24668018 7 69 theme rPPHY 1180:1184 arg1 production 1186:1195 rPPHY production 1180:1195 rPPHY production 1180:1195 The optimization of medium components led to a 21.8-fold improvement in rPPHY production over the endogenous yeast. 24668018 9 70 theme protein 1370:1376 arg1 % 1346:1346 57.1 % 1341:1346 57.1 % of the total secreted protein into the medium 1341:1392 The rPPHY accounts for 57.1 % of the total secreted protein into the medium. 24668018 9 70 theme protein 1370:1376 arg1 protein 1370:1376 the total secreted protein 1351:1376 the total secreted protein into the medium 1351:1392 The rPPHY accounts for 57.1 % of the total secreted protein into the medium. 24668018 5 71 theme endogenous 897:906 arg1 enzyme 908:913 the endogenous enzyme 893:913 the endogenous enzyme 893:913 The temperature and pH optima of rPPHY are 60 °C and 4.0, similar to the endogenous enzyme. 24668018 5 72 theme rPPHY 857:861 arg1 °C 870:871 60 °C 867:871 60 °C 867:871 The temperature and pH optima of rPPHY are 60 °C and 4.0, similar to the endogenous enzyme. 24668018 5 72 theme rPPHY 857:861 arg1 optima 847:852 The temperature and pH optima 824:852 optima 847:852 The temperature and pH optima of rPPHY are 60 °C and 4.0, similar to the endogenous enzyme. 24668018 6 73 theme K 970:970 arg1 m 979:979 m 979:979 m 979:979 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) of rPPHY are 0.2 ± 0.03 mM, 78.2 ± 1.43 nmol mg(-1) s(-1), 65,655 ± 10.92 s(-1), and 328.3 ± 3.12 μM(-1) s(-1), respectively. 24668018 6 73 theme K 970:970 arg1 /K 976:977 K(cat)/K 970:977 K(cat)/K(m) 970:980 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) of rPPHY are 0.2 ± 0.03 mM, 78.2 ± 1.43 nmol mg(-1) s(-1), 65,655 ± 10.92 s(-1), and 328.3 ± 3.12 μM(-1) s(-1), respectively. 24668018 6 73 theme K 970:970 arg1 characteristics 928:942 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) 916:980 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) of rPPHY 916:989 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) of rPPHY are 0.2 ± 0.03 mM, 78.2 ± 1.43 nmol mg(-1) s(-1), 65,655 ± 10.92 s(-1), and 328.3 ± 3.12 μM(-1) s(-1), respectively. 24668018 0 74 from applicability 103:115 arg1 pastoris 86:93 P. pastoris 83:93 P. pastoris 83:93 Optimization of heterologous expression of the phytase (PPHY) of Pichia anomala in P. pastoris and its applicability in fractionating allergenic glycinin from soy protein. 24668018 6 75 theme 3.12 1075:1078 arg1 -1 1089:1090 -1 1089:1090 -1 1089:1090 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) of rPPHY are 0.2 ± 0.03 mM, 78.2 ± 1.43 nmol mg(-1) s(-1), 65,655 ± 10.92 s(-1), and 328.3 ± 3.12 μM(-1) s(-1), respectively. 24668018 6 75 theme 3.12 1075:1078 arg1 s 1087:1087 328.3 ± 3.12 μM(-1) s 1067:1087 328.3 ± 3.12 μM(-1) s(-1) 1067:1091 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) of rPPHY are 0.2 ± 0.03 mM, 78.2 ± 1.43 nmol mg(-1) s(-1), 65,655 ± 10.92 s(-1), and 328.3 ± 3.12 μM(-1) s(-1), respectively. 24668018 1 76 theme additive 384:391 arg1 food 379:382 food 379:382 food additive 379:391 The phytase (PPHY) of Pichia anomala has the requisite properties of thermostability and acidstability, broad substrate spectrum, and protease insensitivity, which make it a suitable candidate as a feed and food additive. 24668018 3 77 theme PPHY 545:548 arg1 copies 535:540 Three copies 529:540 Three copies of PPHY 529:548 Three copies of PPHY have been detected integrated into the chromosomal DNA of the recombinant P. pastoris. 24668018 8 78 theme laboratory 1296:1305 arg1 fermenter 1307:1315 the laboratory fermenter 1292:1315 the laboratory fermenter 1292:1315 The rPPHY titer attained in shake flasks could also be sustained in the laboratory fermenter. 24668018 1 79 theme anomala 201:207 arg1 PPHY 185:188 PPHY 185:188 PPHY 185:188 The phytase (PPHY) of Pichia anomala has the requisite properties of thermostability and acidstability, broad substrate spectrum, and protease insensitivity, which make it a suitable candidate as a feed and food additive. 24668018 1 79 theme anomala 201:207 arg1 phytase 176:182 The phytase 172:182 The phytase (PPHY) of Pichia anomala 172:207 The phytase (PPHY) of Pichia anomala has the requisite properties of thermostability and acidstability, broad substrate spectrum, and protease insensitivity, which make it a suitable candidate as a feed and food additive. 24668018 2 80 theme genomic 447:453 arg1 DNA 455:457 anomala genomic DNA 439:457 P. anomala genomic DNA 436:457 The 1,389-bp PPHY gene was amplified from P. anomala genomic DNA, cloned in pPICZαA, and expressed extracellularly in P. pastoris X33. 24668018 0 81 from expression 29:38 arg1 pastoris 86:93 P. pastoris 83:93 P. pastoris 83:93 Optimization of heterologous expression of the phytase (PPHY) of Pichia anomala in P. pastoris and its applicability in fractionating allergenic glycinin from soy protein. 24668018 6 82 theme rPPHY 985:989 arg1 K 958:958 K 958:958 K(cat) 958:963 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) of rPPHY are 0.2 ± 0.03 mM, 78.2 ± 1.43 nmol mg(-1) s(-1), 65,655 ± 10.92 s(-1), and 328.3 ± 3.12 μM(-1) s(-1), respectively. 24668018 6 82 theme rPPHY 985:989 arg1 mM 1006:1007 0.2 ± 0.03 mM 995:1007 0.2 ± 0.03 mM 995:1007 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) of rPPHY are 0.2 ± 0.03 mM, 78.2 ± 1.43 nmol mg(-1) s(-1), 65,655 ± 10.92 s(-1), and 328.3 ± 3.12 μM(-1) s(-1), respectively. 24668018 6 82 theme rPPHY 985:989 arg1 characteristics 928:942 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) 916:980 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) of rPPHY 916:989 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) of rPPHY are 0.2 ± 0.03 mM, 78.2 ± 1.43 nmol mg(-1) s(-1), 65,655 ± 10.92 s(-1), and 328.3 ± 3.12 μM(-1) s(-1), respectively. 24668018 6 82 theme rPPHY 985:989 arg1 V 950:950 V 950:950 V(max) 950:955 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) of rPPHY are 0.2 ± 0.03 mM, 78.2 ± 1.43 nmol mg(-1) s(-1), 65,655 ± 10.92 s(-1), and 328.3 ± 3.12 μM(-1) s(-1), respectively. 24668018 6 82 theme rPPHY 985:989 arg1 K 944:944 K 944:944 K(m) 944:947 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) of rPPHY are 0.2 ± 0.03 mM, 78.2 ± 1.43 nmol mg(-1) s(-1), 65,655 ± 10.92 s(-1), and 328.3 ± 3.12 μM(-1) s(-1), respectively. 24668018 6 82 theme rPPHY 985:989 arg1 /K 976:977 K(cat)/K 970:977 K(cat)/K(m) 970:980 The kinetic characteristics K(m), V(max), K(cat), and K(cat)/K(m) of rPPHY are 0.2 ± 0.03 mM, 78.2 ± 1.43 nmol mg(-1) s(-1), 65,655 ± 10.92 s(-1), and 328.3 ± 3.12 μM(-1) s(-1), respectively. 24668018 4 83 gly glycoprotein 756:767 arg1 this 732:735 this 732:735 this 732:735 The size exclusion chromatography followed by electrophoresis of the pure rPPHY confirmed that this is a homohexameric glycoprotein of ~420 kDa with a 24.3 % portion as N-linked glycans. 24668018 4 83 gly glycoprotein 756:767 arg1 glycoprotein 756:767 a homohexameric glycoprotein 740:767 a homohexameric glycoprotein of ~420 kDa with a 24.3 % portion as N-linked glycans 740:821 The size exclusion chromatography followed by electrophoresis of the pure rPPHY confirmed that this is a homohexameric glycoprotein of ~420 kDa with a 24.3 % portion as N-linked glycans. 24668018 4 84 with glycoprotein 756:767 arg1 portion 795:801 a 24.3 % portion 786:801 a 24.3 % portion as N-linked glycans 786:821 The size exclusion chromatography followed by electrophoresis of the pure rPPHY confirmed that this is a homohexameric glycoprotein of ~420 kDa with a 24.3 % portion as N-linked glycans. 24381145 7 0 theme verification 1053:1064 arg1 experiments 1066:1076 verification experiments 1053:1076 verification experiments 1053:1076 After identifying the optimal conditions for cell line A, we performed verification experiments in fed-batch bioreactors for cell lines A and B. 24381145 2 1 theme deacetylase 349:359 arg1 inhibitors 368:377 histone deacetylase (HDAC) inhibitors 341:377 histone deacetylase (HDAC) inhibitors 341:377 One method for increasing CHO cell productivity is the addition of histone deacetylase (HDAC) inhibitors to the cell culture process. 24381145 1 2 theme capacity 252:259 arg1 utilization 261:271 more efficient manufacturing capacity utilization 223:271 more efficient manufacturing capacity utilization 223:271 Improving the productivity of a biopharmaceutical Chinese hamster ovary (CHO) fed-batch cell culture can enable cost savings and more efficient manufacturing capacity utilization. 24381145 3 3 theme carboxylic 511:520 arg1 acid 522:525 branched-chain carboxylic acid 496:525 a branched-chain carboxylic acid HDAC inhibitor 494:540 In this study, we examined the effect of valproic acid (VPA, 2-propylpentanoic acid), a branched-chain carboxylic acid HDAC inhibitor, on the productivity of three of our CHO cell lines that stably express monoclonal antibodies. 24381145 5 4 dep line 753:756 arg1 A 758:758 A 758:758 A 758:758 Cell line A responded highly positively, cell line B responded mildly positively, and cell line C did not respond. 24381145 8 5 theme VPA 1175:1177 arg1 dose 1167:1170 a high dose 1160:1170 a high dose of VPA late in the culture 1160:1197 These experiments confirmed that a high dose of VPA late in the culture can increase harvest titer >20 % without greatly changing antibody aggregation, charge heterogeneity, and N-linked glycosylation profiles. 24381145 7 6 theme cell 1027:1030 arg1 A 1037:1037 cell line A 1027:1037 cell line A 1027:1037 After identifying the optimal conditions for cell line A, we performed verification experiments in fed-batch bioreactors for cell lines A and B. 24381145 1 7 theme cell 182:185 arg1 culture 187:193 a biopharmaceutical Chinese hamster ovary (CHO) fed-batch cell culture 124:193 a biopharmaceutical Chinese hamster ovary (CHO) fed-batch cell culture 124:193 Improving the productivity of a biopharmaceutical Chinese hamster ovary (CHO) fed-batch cell culture can enable cost savings and more efficient manufacturing capacity utilization. 24381145 8 8 theme charge 1279:1284 arg1 heterogeneity 1286:1298 charge heterogeneity 1279:1298 charge heterogeneity 1279:1298 These experiments confirmed that a high dose of VPA late in the culture can increase harvest titer >20 % without greatly changing antibody aggregation, charge heterogeneity, and N-linked glycosylation profiles. 24381145 3 9 theme HDAC 527:530 arg1 inhibitor 532:540 a branched-chain carboxylic acid HDAC inhibitor 494:540 a branched-chain carboxylic acid HDAC inhibitor 494:540 In this study, we examined the effect of valproic acid (VPA, 2-propylpentanoic acid), a branched-chain carboxylic acid HDAC inhibitor, on the productivity of three of our CHO cell lines that stably express monoclonal antibodies. 24381145 3 9 theme HDAC 527:530 arg1 acid 458:461 valproic acid 449:461 valproic acid (VPA, 2-propylpentanoic acid) 449:491 In this study, we examined the effect of valproic acid (VPA, 2-propylpentanoic acid), a branched-chain carboxylic acid HDAC inhibitor, on the productivity of three of our CHO cell lines that stably express monoclonal antibodies. 24381145 9 10 theme viable 1388:1393 arg1 enhancer 1410:1417 an attractive and viable small molecule enhancer 1370:1417 an attractive and viable small molecule enhancer of protein production for biopharmaceutical CHO cell culture processes 1370:1488 Our results suggest that VPA is an attractive and viable small molecule enhancer of protein production for biopharmaceutical CHO cell culture processes. 24381145 9 10 theme viable 1388:1393 arg1 VPA 1363:1365 VPA 1363:1365 VPA 1363:1365 Our results suggest that VPA is an attractive and viable small molecule enhancer of protein production for biopharmaceutical CHO cell culture processes. 24381145 8 11 from VPA 1175:1177 arg1 culture 1191:1197 the culture 1187:1197 the culture 1187:1197 These experiments confirmed that a high dose of VPA late in the culture can increase harvest titer >20 % without greatly changing antibody aggregation, charge heterogeneity, and N-linked glycosylation profiles. 24381145 9 12 theme molecule 1401:1408 arg1 enhancer 1410:1417 an attractive and viable small molecule enhancer 1370:1417 an attractive and viable small molecule enhancer of protein production for biopharmaceutical CHO cell culture processes 1370:1488 Our results suggest that VPA is an attractive and viable small molecule enhancer of protein production for biopharmaceutical CHO cell culture processes. 24381145 9 12 theme molecule 1401:1408 arg1 VPA 1363:1365 VPA 1363:1365 VPA 1363:1365 Our results suggest that VPA is an attractive and viable small molecule enhancer of protein production for biopharmaceutical CHO cell culture processes. 24381145 6 13 theme factorial 881:889 arg1 experiments 891:901 factorial experiments 881:901 factorial experiments 881:901 We then performed factorial experiments to identify the optimal VPA concentration and day of addition for cell line A. 24381145 8 14 from dose 1167:1170 arg1 culture 1191:1197 the culture 1187:1197 the culture 1187:1197 These experiments confirmed that a high dose of VPA late in the culture can increase harvest titer >20 % without greatly changing antibody aggregation, charge heterogeneity, and N-linked glycosylation profiles. 24381145 8 15 theme titer 1220:1224 arg1 % 1230:1230 harvest titer >20 % 1212:1230 harvest titer >20 % 1212:1230 These experiments confirmed that a high dose of VPA late in the culture can increase harvest titer >20 % without greatly changing antibody aggregation, charge heterogeneity, and N-linked glycosylation profiles. 24381145 3 16 theme CHO 579:581 arg1 lines 588:592 our CHO cell lines 575:592 our CHO cell lines that stably express monoclonal antibodies 575:634 In this study, we examined the effect of valproic acid (VPA, 2-propylpentanoic acid), a branched-chain carboxylic acid HDAC inhibitor, on the productivity of three of our CHO cell lines that stably express monoclonal antibodies. 24381145 8 17 from culture 1191:1197 arg1 dose 1167:1170 a high dose 1160:1170 a high dose of VPA late in the culture 1160:1197 These experiments confirmed that a high dose of VPA late in the culture can increase harvest titer >20 % without greatly changing antibody aggregation, charge heterogeneity, and N-linked glycosylation profiles. 24381145 9 18 theme production 1430:1439 arg1 enhancer 1410:1417 an attractive and viable small molecule enhancer 1370:1417 an attractive and viable small molecule enhancer of protein production for biopharmaceutical CHO cell culture processes 1370:1488 Our results suggest that VPA is an attractive and viable small molecule enhancer of protein production for biopharmaceutical CHO cell culture processes. 24381145 9 18 theme production 1430:1439 arg1 VPA 1363:1365 VPA 1363:1365 VPA 1363:1365 Our results suggest that VPA is an attractive and viable small molecule enhancer of protein production for biopharmaceutical CHO cell culture processes. 24381145 4 19 theme shake 647:651 arg1 titrations 663:672 Fed-batch shake flask VPA titrations 637:672 Fed-batch shake flask VPA titrations on the three different CHO cell lines 637:710 Fed-batch shake flask VPA titrations on the three different CHO cell lines yielded cell line-specific results. 24381145 7 20 theme cell 1107:1110 arg1 lines 1112:1116 cell lines A and B 1107:1124 cell lines A and B 1107:1124 After identifying the optimal conditions for cell line A, we performed verification experiments in fed-batch bioreactors for cell lines A and B. 24381145 7 20 theme cell 1107:1110 arg1 B 1124:1124 B 1124:1124 B 1124:1124 After identifying the optimal conditions for cell line A, we performed verification experiments in fed-batch bioreactors for cell lines A and B. 24381145 7 20 theme cell 1107:1110 arg1 A 1118:1118 A 1118:1118 A 1118:1118 After identifying the optimal conditions for cell line A, we performed verification experiments in fed-batch bioreactors for cell lines A and B. 24381145 1 21 theme hamster 152:158 arg1 CHO 167:169 CHO 167:169 CHO 167:169 Improving the productivity of a biopharmaceutical Chinese hamster ovary (CHO) fed-batch cell culture can enable cost savings and more efficient manufacturing capacity utilization. 24381145 1 21 theme hamster 152:158 arg1 ovary 160:164 Chinese hamster ovary 144:164 a biopharmaceutical Chinese hamster ovary (CHO) fed-batch cell culture 124:193 Improving the productivity of a biopharmaceutical Chinese hamster ovary (CHO) fed-batch cell culture can enable cost savings and more efficient manufacturing capacity utilization. 24381145 8 22 link N-linked 1305:1312 arg1 profiles 1328:1335 N-linked glycosylation profiles 1305:1335 N-linked glycosylation profiles 1305:1335 These experiments confirmed that a high dose of VPA late in the culture can increase harvest titer >20 % without greatly changing antibody aggregation, charge heterogeneity, and N-linked glycosylation profiles. 24381145 4 23 theme VPA 659:661 arg1 titrations 663:672 Fed-batch shake flask VPA titrations 637:672 Fed-batch shake flask VPA titrations on the three different CHO cell lines 637:710 Fed-batch shake flask VPA titrations on the three different CHO cell lines yielded cell line-specific results. 24381145 0 24 theme monoclonal 66:75 arg1 titers 86:91 monoclonal antibody titers 66:91 monoclonal antibody titers 66:91 Addition of valproic acid to CHO cell fed-batch cultures improves monoclonal antibody titers. 24381145 9 25 theme cell 1467:1470 arg1 processes 1480:1488 biopharmaceutical CHO cell culture processes 1445:1488 biopharmaceutical CHO cell culture processes 1445:1488 Our results suggest that VPA is an attractive and viable small molecule enhancer of protein production for biopharmaceutical CHO cell culture processes. 24381145 7 26 dep lines 1112:1116 arg1 lines 1112:1116 cell lines A and B 1107:1124 cell lines A and B 1107:1124 After identifying the optimal conditions for cell line A, we performed verification experiments in fed-batch bioreactors for cell lines A and B. 24381145 7 26 dep lines 1112:1116 arg1 B 1124:1124 B 1124:1124 B 1124:1124 After identifying the optimal conditions for cell line A, we performed verification experiments in fed-batch bioreactors for cell lines A and B. 24381145 7 26 dep lines 1112:1116 arg1 A 1118:1118 A 1118:1118 A 1118:1118 After identifying the optimal conditions for cell line A, we performed verification experiments in fed-batch bioreactors for cell lines A and B. 24381145 8 27 theme antibody 1257:1264 arg1 aggregation 1266:1276 antibody aggregation 1257:1276 antibody aggregation 1257:1276 These experiments confirmed that a high dose of VPA late in the culture can increase harvest titer >20 % without greatly changing antibody aggregation, charge heterogeneity, and N-linked glycosylation profiles. 24381145 4 28 theme cell 701:704 arg1 lines 706:710 the three different CHO cell lines 677:710 the three different CHO cell lines 677:710 Fed-batch shake flask VPA titrations on the three different CHO cell lines yielded cell line-specific results. 24381145 3 29 dep acid 458:461 arg1 VPA 464:466 VPA 464:466 VPA 464:466 In this study, we examined the effect of valproic acid (VPA, 2-propylpentanoic acid), a branched-chain carboxylic acid HDAC inhibitor, on the productivity of three of our CHO cell lines that stably express monoclonal antibodies. 24381145 3 29 dep acid 458:461 arg1 acid 487:490 2-propylpentanoic acid 469:490 2-propylpentanoic acid 469:490 In this study, we examined the effect of valproic acid (VPA, 2-propylpentanoic acid), a branched-chain carboxylic acid HDAC inhibitor, on the productivity of three of our CHO cell lines that stably express monoclonal antibodies. 24381145 6 30 theme VPA 927:929 arg1 concentration 931:943 the optimal VPA concentration 915:943 the optimal VPA concentration 915:943 We then performed factorial experiments to identify the optimal VPA concentration and day of addition for cell line A. 24381145 2 31 theme cell 386:389 arg1 process 399:405 the cell culture process 382:405 the cell culture process 382:405 One method for increasing CHO cell productivity is the addition of histone deacetylase (HDAC) inhibitors to the cell culture process. 24381145 0 32 theme CHO 29:31 arg1 cultures 48:55 CHO cell fed-batch cultures 29:55 CHO cell fed-batch cultures 29:55 Addition of valproic acid to CHO cell fed-batch cultures improves monoclonal antibody titers. 24381145 1 33 theme biopharmaceutical 126:142 arg1 culture 187:193 a biopharmaceutical Chinese hamster ovary (CHO) fed-batch cell culture 124:193 a biopharmaceutical Chinese hamster ovary (CHO) fed-batch cell culture 124:193 Improving the productivity of a biopharmaceutical Chinese hamster ovary (CHO) fed-batch cell culture can enable cost savings and more efficient manufacturing capacity utilization. 24381145 4 34 theme CHO 697:699 arg1 lines 706:710 the three different CHO cell lines 677:710 the three different CHO cell lines 677:710 Fed-batch shake flask VPA titrations on the three different CHO cell lines yielded cell line-specific results. 24381145 0 35 theme valproic 12:19 arg1 acid 21:24 valproic acid 12:24 valproic acid 12:24 Addition of valproic acid to CHO cell fed-batch cultures improves monoclonal antibody titers. 24381145 1 36 theme Chinese 144:150 arg1 CHO 167:169 CHO 167:169 CHO 167:169 Improving the productivity of a biopharmaceutical Chinese hamster ovary (CHO) fed-batch cell culture can enable cost savings and more efficient manufacturing capacity utilization. 24381145 1 36 theme Chinese 144:150 arg1 ovary 160:164 Chinese hamster ovary 144:164 a biopharmaceutical Chinese hamster ovary (CHO) fed-batch cell culture 124:193 Improving the productivity of a biopharmaceutical Chinese hamster ovary (CHO) fed-batch cell culture can enable cost savings and more efficient manufacturing capacity utilization. 24381145 8 37 theme glycosylation 1314:1326 arg1 profiles 1328:1335 N-linked glycosylation profiles 1305:1335 N-linked glycosylation profiles 1305:1335 These experiments confirmed that a high dose of VPA late in the culture can increase harvest titer >20 % without greatly changing antibody aggregation, charge heterogeneity, and N-linked glycosylation profiles. 24381145 5 38 theme Cell 748:751 arg1 line 753:756 Cell line 748:756 Cell line A 748:758 Cell line A responded highly positively, cell line B responded mildly positively, and cell line C did not respond. 24381145 6 39 theme line 974:977 arg1 A 979:979 cell line A 969:979 cell line A 969:979 We then performed factorial experiments to identify the optimal VPA concentration and day of addition for cell line A. 24381145 3 40 theme lines 588:592 arg1 lines 588:592 our CHO cell lines 575:592 our CHO cell lines that stably express monoclonal antibodies 575:634 In this study, we examined the effect of valproic acid (VPA, 2-propylpentanoic acid), a branched-chain carboxylic acid HDAC inhibitor, on the productivity of three of our CHO cell lines that stably express monoclonal antibodies. 24381145 3 40 theme lines 588:592 arg1 three 566:570 three 566:570 three 566:570 In this study, we examined the effect of valproic acid (VPA, 2-propylpentanoic acid), a branched-chain carboxylic acid HDAC inhibitor, on the productivity of three of our CHO cell lines that stably express monoclonal antibodies. 24381145 2 41 theme histone 341:347 arg1 HDAC 362:365 HDAC 362:365 HDAC 362:365 One method for increasing CHO cell productivity is the addition of histone deacetylase (HDAC) inhibitors to the cell culture process. 24381145 2 41 theme histone 341:347 arg1 deacetylase 349:359 histone deacetylase 341:359 histone deacetylase (HDAC) inhibitors 341:377 One method for increasing CHO cell productivity is the addition of histone deacetylase (HDAC) inhibitors to the cell culture process. 24381145 0 42 theme cell 33:36 arg1 cultures 48:55 CHO cell fed-batch cultures 29:55 CHO cell fed-batch cultures 29:55 Addition of valproic acid to CHO cell fed-batch cultures improves monoclonal antibody titers. 24381145 3 43 theme valproic 449:456 arg1 inhibitor 532:540 a branched-chain carboxylic acid HDAC inhibitor 494:540 a branched-chain carboxylic acid HDAC inhibitor 494:540 In this study, we examined the effect of valproic acid (VPA, 2-propylpentanoic acid), a branched-chain carboxylic acid HDAC inhibitor, on the productivity of three of our CHO cell lines that stably express monoclonal antibodies. 24381145 3 43 theme valproic 449:456 arg1 acid 458:461 valproic acid 449:461 valproic acid (VPA, 2-propylpentanoic acid) 449:491 In this study, we examined the effect of valproic acid (VPA, 2-propylpentanoic acid), a branched-chain carboxylic acid HDAC inhibitor, on the productivity of three of our CHO cell lines that stably express monoclonal antibodies. 24381145 9 44 theme biopharmaceutical 1445:1461 arg1 processes 1480:1488 biopharmaceutical CHO cell culture processes 1445:1488 biopharmaceutical CHO cell culture processes 1445:1488 Our results suggest that VPA is an attractive and viable small molecule enhancer of protein production for biopharmaceutical CHO cell culture processes. 24381145 3 45 theme monoclonal 614:623 arg1 antibodies 625:634 monoclonal antibodies 614:634 monoclonal antibodies 614:634 In this study, we examined the effect of valproic acid (VPA, 2-propylpentanoic acid), a branched-chain carboxylic acid HDAC inhibitor, on the productivity of three of our CHO cell lines that stably express monoclonal antibodies. 24381145 4 46 from titrations 663:672 arg1 lines 706:710 the three different CHO cell lines 677:710 the three different CHO cell lines 677:710 Fed-batch shake flask VPA titrations on the three different CHO cell lines yielded cell line-specific results. 24381145 1 47 theme manufacturing 238:250 arg1 utilization 261:271 more efficient manufacturing capacity utilization 223:271 more efficient manufacturing capacity utilization 223:271 Improving the productivity of a biopharmaceutical Chinese hamster ovary (CHO) fed-batch cell culture can enable cost savings and more efficient manufacturing capacity utilization. 24381145 3 48 theme branched-chain 496:509 arg1 acid 522:525 branched-chain carboxylic acid 496:525 a branched-chain carboxylic acid HDAC inhibitor 494:540 In this study, we examined the effect of valproic acid (VPA, 2-propylpentanoic acid), a branched-chain carboxylic acid HDAC inhibitor, on the productivity of three of our CHO cell lines that stably express monoclonal antibodies. 24381145 9 49 theme CHO 1463:1465 arg1 processes 1480:1488 biopharmaceutical CHO cell culture processes 1445:1488 biopharmaceutical CHO cell culture processes 1445:1488 Our results suggest that VPA is an attractive and viable small molecule enhancer of protein production for biopharmaceutical CHO cell culture processes. 24381145 7 50 theme line 1032:1035 arg1 A 1037:1037 cell line A 1027:1037 cell line A 1027:1037 After identifying the optimal conditions for cell line A, we performed verification experiments in fed-batch bioreactors for cell lines A and B. 24381145 8 51 theme high 1162:1165 arg1 dose 1167:1170 a high dose 1160:1170 a high dose of VPA late in the culture 1160:1197 These experiments confirmed that a high dose of VPA late in the culture can increase harvest titer >20 % without greatly changing antibody aggregation, charge heterogeneity, and N-linked glycosylation profiles. 24381145 1 52 theme fed-batch 172:180 arg1 culture 187:193 a biopharmaceutical Chinese hamster ovary (CHO) fed-batch cell culture 124:193 a biopharmaceutical Chinese hamster ovary (CHO) fed-batch cell culture 124:193 Improving the productivity of a biopharmaceutical Chinese hamster ovary (CHO) fed-batch cell culture can enable cost savings and more efficient manufacturing capacity utilization. 24381145 6 53 theme optimal 919:925 arg1 concentration 931:943 the optimal VPA concentration 915:943 the optimal VPA concentration 915:943 We then performed factorial experiments to identify the optimal VPA concentration and day of addition for cell line A. 24381145 7 54 theme optimal 1004:1010 arg1 conditions 1012:1021 the optimal conditions 1000:1021 the optimal conditions for cell line A 1000:1037 After identifying the optimal conditions for cell line A, we performed verification experiments in fed-batch bioreactors for cell lines A and B. 24381145 2 55 theme cell 304:307 arg1 productivity 309:320 CHO cell productivity 300:320 CHO cell productivity 300:320 One method for increasing CHO cell productivity is the addition of histone deacetylase (HDAC) inhibitors to the cell culture process. 24381145 1 56 theme culture 187:193 arg1 productivity 108:119 the productivity 104:119 the productivity of a biopharmaceutical Chinese hamster ovary (CHO) fed-batch cell culture 104:193 Improving the productivity of a biopharmaceutical Chinese hamster ovary (CHO) fed-batch cell culture can enable cost savings and more efficient manufacturing capacity utilization. 24381145 8 57 theme late 1179:1182 arg1 VPA 1175:1177 VPA late 1175:1182 VPA late in the culture 1175:1197 These experiments confirmed that a high dose of VPA late in the culture can increase harvest titer >20 % without greatly changing antibody aggregation, charge heterogeneity, and N-linked glycosylation profiles. 24381145 9 58 theme attractive 1373:1382 arg1 enhancer 1410:1417 an attractive and viable small molecule enhancer 1370:1417 an attractive and viable small molecule enhancer of protein production for biopharmaceutical CHO cell culture processes 1370:1488 Our results suggest that VPA is an attractive and viable small molecule enhancer of protein production for biopharmaceutical CHO cell culture processes. 24381145 9 58 theme attractive 1373:1382 arg1 VPA 1363:1365 VPA 1363:1365 VPA 1363:1365 Our results suggest that VPA is an attractive and viable small molecule enhancer of protein production for biopharmaceutical CHO cell culture processes. 24381145 9 59 theme small 1395:1399 arg1 enhancer 1410:1417 an attractive and viable small molecule enhancer 1370:1417 an attractive and viable small molecule enhancer of protein production for biopharmaceutical CHO cell culture processes 1370:1488 Our results suggest that VPA is an attractive and viable small molecule enhancer of protein production for biopharmaceutical CHO cell culture processes. 24381145 9 59 theme small 1395:1399 arg1 VPA 1363:1365 VPA 1363:1365 VPA 1363:1365 Our results suggest that VPA is an attractive and viable small molecule enhancer of protein production for biopharmaceutical CHO cell culture processes. 24381145 9 60 theme protein 1422:1428 arg1 production 1430:1439 protein production 1422:1439 protein production 1422:1439 Our results suggest that VPA is an attractive and viable small molecule enhancer of protein production for biopharmaceutical CHO cell culture processes. 24381145 3 61 theme acid 522:525 arg1 inhibitor 532:540 a branched-chain carboxylic acid HDAC inhibitor 494:540 a branched-chain carboxylic acid HDAC inhibitor 494:540 In this study, we examined the effect of valproic acid (VPA, 2-propylpentanoic acid), a branched-chain carboxylic acid HDAC inhibitor, on the productivity of three of our CHO cell lines that stably express monoclonal antibodies. 24381145 3 61 theme acid 522:525 arg1 acid 458:461 valproic acid 449:461 valproic acid (VPA, 2-propylpentanoic acid) 449:491 In this study, we examined the effect of valproic acid (VPA, 2-propylpentanoic acid), a branched-chain carboxylic acid HDAC inhibitor, on the productivity of three of our CHO cell lines that stably express monoclonal antibodies. 24381145 6 62 theme cell 969:972 arg1 A 979:979 cell line A 969:979 cell line A 969:979 We then performed factorial experiments to identify the optimal VPA concentration and day of addition for cell line A. 24381145 8 63 theme harvest 1212:1218 arg1 % 1230:1230 harvest titer >20 % 1212:1230 harvest titer >20 % 1212:1230 These experiments confirmed that a high dose of VPA late in the culture can increase harvest titer >20 % without greatly changing antibody aggregation, charge heterogeneity, and N-linked glycosylation profiles. 24381145 3 64 theme three 566:570 arg1 productivity 550:561 the productivity 546:561 the productivity of three of our CHO cell lines that stably express monoclonal antibodies 546:634 In this study, we examined the effect of valproic acid (VPA, 2-propylpentanoic acid), a branched-chain carboxylic acid HDAC inhibitor, on the productivity of three of our CHO cell lines that stably express monoclonal antibodies. 24381145 5 65 theme cell 789:792 arg1 line 794:797 cell line 789:797 cell line B 789:799 Cell line A responded highly positively, cell line B responded mildly positively, and cell line C did not respond. 24381145 5 66 theme cell 834:837 arg1 line 839:842 cell line 834:842 cell line C 834:844 Cell line A responded highly positively, cell line B responded mildly positively, and cell line C did not respond. 24381145 6 67 theme addition 956:963 arg1 day 949:951 day 949:951 day of addition for cell line A 949:979 We then performed factorial experiments to identify the optimal VPA concentration and day of addition for cell line A. 24381145 6 67 theme addition 956:963 arg1 concentration 931:943 the optimal VPA concentration 915:943 the optimal VPA concentration 915:943 We then performed factorial experiments to identify the optimal VPA concentration and day of addition for cell line A. 24381145 4 68 theme Fed-batch 637:645 arg1 titrations 663:672 Fed-batch shake flask VPA titrations 637:672 Fed-batch shake flask VPA titrations on the three different CHO cell lines 637:710 Fed-batch shake flask VPA titrations on the three different CHO cell lines yielded cell line-specific results. 24381145 0 69 theme antibody 77:84 arg1 titers 86:91 monoclonal antibody titers 66:91 monoclonal antibody titers 66:91 Addition of valproic acid to CHO cell fed-batch cultures improves monoclonal antibody titers. 24381145 1 70 theme ovary 160:164 arg1 culture 187:193 a biopharmaceutical Chinese hamster ovary (CHO) fed-batch cell culture 124:193 a biopharmaceutical Chinese hamster ovary (CHO) fed-batch cell culture 124:193 Improving the productivity of a biopharmaceutical Chinese hamster ovary (CHO) fed-batch cell culture can enable cost savings and more efficient manufacturing capacity utilization. 24381145 4 71 theme flask 653:657 arg1 titrations 663:672 Fed-batch shake flask VPA titrations 637:672 Fed-batch shake flask VPA titrations on the three different CHO cell lines 637:710 Fed-batch shake flask VPA titrations on the three different CHO cell lines yielded cell line-specific results. 24381145 9 72 theme culture 1472:1478 arg1 processes 1480:1488 biopharmaceutical CHO cell culture processes 1445:1488 biopharmaceutical CHO cell culture processes 1445:1488 Our results suggest that VPA is an attractive and viable small molecule enhancer of protein production for biopharmaceutical CHO cell culture processes. 24381145 2 73 theme CHO 300:302 arg1 productivity 309:320 CHO cell productivity 300:320 CHO cell productivity 300:320 One method for increasing CHO cell productivity is the addition of histone deacetylase (HDAC) inhibitors to the cell culture process. 24381145 4 74 theme line-specific 725:737 arg1 results 739:745 cell line-specific results 720:745 cell line-specific results 720:745 Fed-batch shake flask VPA titrations on the three different CHO cell lines yielded cell line-specific results. 24381145 4 75 theme different 687:695 arg1 lines 706:710 the three different CHO cell lines 677:710 the three different CHO cell lines 677:710 Fed-batch shake flask VPA titrations on the three different CHO cell lines yielded cell line-specific results. 24381145 2 76 theme inhibitors 368:377 arg1 addition 329:336 the addition 325:336 the addition of histone deacetylase (HDAC) inhibitors to the cell culture process 325:405 One method for increasing CHO cell productivity is the addition of histone deacetylase (HDAC) inhibitors to the cell culture process. 24381145 2 76 theme inhibitors 368:377 arg1 method 278:283 One method 274:283 One method for increasing CHO cell productivity 274:320 One method for increasing CHO cell productivity is the addition of histone deacetylase (HDAC) inhibitors to the cell culture process. 24381145 0 77 theme acid 21:24 arg1 Addition 0:7 Addition 0:7 Addition of valproic acid to CHO cell fed-batch cultures 0:55 Addition of valproic acid to CHO cell fed-batch cultures improves monoclonal antibody titers. 24381145 5 78 dep line 839:842 arg1 C 844:844 C 844:844 cell line C 834:844 Cell line A responded highly positively, cell line B responded mildly positively, and cell line C did not respond. 24381145 7 79 theme fed-batch 1081:1089 arg1 bioreactors 1091:1101 fed-batch bioreactors 1081:1101 fed-batch bioreactors for cell lines A and B 1081:1124 After identifying the optimal conditions for cell line A, we performed verification experiments in fed-batch bioreactors for cell lines A and B. 24381145 3 80 theme cell 583:586 arg1 lines 588:592 our CHO cell lines 575:592 our CHO cell lines that stably express monoclonal antibodies 575:634 In this study, we examined the effect of valproic acid (VPA, 2-propylpentanoic acid), a branched-chain carboxylic acid HDAC inhibitor, on the productivity of three of our CHO cell lines that stably express monoclonal antibodies. 24381145 8 81 theme N-linked 1305:1312 arg1 profiles 1328:1335 N-linked glycosylation profiles 1305:1335 N-linked glycosylation profiles 1305:1335 These experiments confirmed that a high dose of VPA late in the culture can increase harvest titer >20 % without greatly changing antibody aggregation, charge heterogeneity, and N-linked glycosylation profiles. 24381145 2 82 theme culture 391:397 arg1 process 399:405 the cell culture process 382:405 the cell culture process 382:405 One method for increasing CHO cell productivity is the addition of histone deacetylase (HDAC) inhibitors to the cell culture process. 24381145 0 83 theme fed-batch 38:46 arg1 cultures 48:55 CHO cell fed-batch cultures 29:55 CHO cell fed-batch cultures 29:55 Addition of valproic acid to CHO cell fed-batch cultures improves monoclonal antibody titers. 24381145 3 84 from effect 439:444 arg1 productivity 550:561 the productivity 546:561 the productivity of three of our CHO cell lines that stably express monoclonal antibodies 546:634 In this study, we examined the effect of valproic acid (VPA, 2-propylpentanoic acid), a branched-chain carboxylic acid HDAC inhibitor, on the productivity of three of our CHO cell lines that stably express monoclonal antibodies. 24381145 3 85 theme 2-propylpentanoic 469:485 arg1 VPA 464:466 VPA 464:466 VPA 464:466 In this study, we examined the effect of valproic acid (VPA, 2-propylpentanoic acid), a branched-chain carboxylic acid HDAC inhibitor, on the productivity of three of our CHO cell lines that stably express monoclonal antibodies. 24381145 3 85 theme 2-propylpentanoic 469:485 arg1 acid 487:490 2-propylpentanoic acid 469:490 2-propylpentanoic acid 469:490 In this study, we examined the effect of valproic acid (VPA, 2-propylpentanoic acid), a branched-chain carboxylic acid HDAC inhibitor, on the productivity of three of our CHO cell lines that stably express monoclonal antibodies. 24381145 3 86 theme acid 458:461 arg1 effect 439:444 the effect 435:444 the effect of valproic acid (VPA, 2-propylpentanoic acid), a branched-chain carboxylic acid HDAC inhibitor, on the productivity of three of our CHO cell lines that stably express monoclonal antibodies 435:634 In this study, we examined the effect of valproic acid (VPA, 2-propylpentanoic acid), a branched-chain carboxylic acid HDAC inhibitor, on the productivity of three of our CHO cell lines that stably express monoclonal antibodies. 24381145 1 87 theme cost 206:209 arg1 savings 211:217 cost savings 206:217 cost savings 206:217 Improving the productivity of a biopharmaceutical Chinese hamster ovary (CHO) fed-batch cell culture can enable cost savings and more efficient manufacturing capacity utilization. 24381145 5 88 dep line 794:797 arg1 B 799:799 B 799:799 cell line B 789:799 Cell line A responded highly positively, cell line B responded mildly positively, and cell line C did not respond. 24381145 1 89 theme efficient 228:236 arg1 utilization 261:271 more efficient manufacturing capacity utilization 223:271 more efficient manufacturing capacity utilization 223:271 Improving the productivity of a biopharmaceutical Chinese hamster ovary (CHO) fed-batch cell culture can enable cost savings and more efficient manufacturing capacity utilization. 24252626 6 0 theme adhesion 1300:1307 arg1 binding 1317:1323 cell adhesion protein binding 1295:1323 cell adhesion protein binding 1295:1323 All rings populated non-chair shapes and the stacked galactose and fucose pyranoses of sLe(a) and sLe(x) were rigidified, suggesting an exploitable 3D-signature of cell adhesion protein binding. 24252626 8 1 theme novel 1696:1700 arg1 entities 1711:1718 carbohydrate-based novel chemical entities 1677:1718 carbohydrate-based novel chemical entities 1677:1718 This simulation protocol, which yields conformational ensembles that are independent of initial 3D-structure, is proposed as a route to understanding oligosaccharide recognition and structure-activity relationships, toward development of carbohydrate-based novel chemical entities. 24252626 4 2 theme secondary 863:871 arg1 structure 873:881 secondary structure 863:881 secondary structure 863:881 Glycosidic linkage and pyranose ring flexing were affected by branching, linkage position, and secondary structure, implicating sequence dependent motions in glycomic functional diversity. 24252626 7 3 theme aqueous 1419:1425 arg1 conformers 1427:1436 all aqueous conformers 1415:1436 all aqueous conformers 1415:1436 Analyses of sLe(x) dynamics over 25μs revealed that only 10μs were sufficient to explore all aqueous conformers. 24252626 6 4 theme exploitable 1267:1277 arg1 3D-signature 1279:1290 an exploitable 3D-signature 1264:1290 an exploitable 3D-signature of cell adhesion protein binding 1264:1323 All rings populated non-chair shapes and the stacked galactose and fucose pyranoses of sLe(a) and sLe(x) were rigidified, suggesting an exploitable 3D-signature of cell adhesion protein binding. 24252626 1 5 theme 3D-structural 190:202 arg1 information 204:214 3D-structural information 190:214 3D-structural information 190:214 The human glycome comprises a vast untapped repository of 3D-structural information that holds the key to glycan recognition and a new era of rationally designed mimetic chemical probes, drugs, and biomaterials. 24252626 2 6 from prediction 359:368 arg1 equilibrium 452:462 thermodynamic equilibrium 438:462 thermodynamic equilibrium 438:462 Toward routine prediction of oligosaccharide conformational populations and exchange rates at thermodynamic equilibrium, we apply hardware-accelerated aqueous molecular dynamics to model μs motions in N-glycans that underpin inflammation and immunity. 24252626 6 7 theme fucose 1198:1203 arg1 pyranoses 1205:1213 the stacked galactose and fucose pyranoses 1172:1213 pyranoses 1205:1213 All rings populated non-chair shapes and the stacked galactose and fucose pyranoses of sLe(a) and sLe(x) were rigidified, suggesting an exploitable 3D-signature of cell adhesion protein binding. 24252626 5 8 dep conventional 1059:1070 arg1 ns 1073:1074 ns 1073:1074 ns 1073:1074 Linkage and ring conformational transitions that have eluded precise quantification by experiment and conventional (ns) simulations were predicted to occur on μs timescales. 24252626 5 9 theme μs 1116:1117 arg1 timescales 1119:1128 μs timescales 1116:1128 μs timescales 1116:1128 Linkage and ring conformational transitions that have eluded precise quantification by experiment and conventional (ns) simulations were predicted to occur on μs timescales. 24252626 3 10 theme 10μs 599:602 arg1 simulations 604:614 10μs simulations 599:614 10μs simulations 599:614 In 10μs simulations, conformational equilibria of mannosyl cores, sialyl Lewis (sLe) antennae, and constituent sub-sequences agreed with prior refinements (X-ray and NMR). 24252626 8 11 theme simulation 1444:1453 arg1 route 1566:1570 a route 1564:1570 a route to understanding oligosaccharide recognition and structure-activity relationships, toward development of carbohydrate-based novel chemical entities 1564:1718 This simulation protocol, which yields conformational ensembles that are independent of initial 3D-structure, is proposed as a route to understanding oligosaccharide recognition and structure-activity relationships, toward development of carbohydrate-based novel chemical entities. 24252626 8 11 theme simulation 1444:1453 arg1 protocol 1455:1462 This simulation protocol 1439:1462 This simulation protocol 1439:1462 This simulation protocol, which yields conformational ensembles that are independent of initial 3D-structure, is proposed as a route to understanding oligosaccharide recognition and structure-activity relationships, toward development of carbohydrate-based novel chemical entities. 24252626 3 12 theme mannosyl 646:653 arg1 cores 655:659 mannosyl cores 646:659 mannosyl cores 646:659 In 10μs simulations, conformational equilibria of mannosyl cores, sialyl Lewis (sLe) antennae, and constituent sub-sequences agreed with prior refinements (X-ray and NMR). 24252626 4 13 theme glycomic 926:933 arg1 diversity 946:954 glycomic functional diversity 926:954 glycomic functional diversity 926:954 Glycosidic linkage and pyranose ring flexing were affected by branching, linkage position, and secondary structure, implicating sequence dependent motions in glycomic functional diversity. 24252626 5 14 theme Linkage 957:963 arg1 transitions 989:999 Linkage and ring conformational transitions 957:999 Linkage and ring conformational transitions that have eluded precise quantification by experiment and conventional (ns) simulations 957:1087 Linkage and ring conformational transitions that have eluded precise quantification by experiment and conventional (ns) simulations were predicted to occur on μs timescales. 24252626 6 15 theme binding 1317:1323 arg1 3D-signature 1279:1290 an exploitable 3D-signature 1264:1290 an exploitable 3D-signature of cell adhesion protein binding 1264:1323 All rings populated non-chair shapes and the stacked galactose and fucose pyranoses of sLe(a) and sLe(x) were rigidified, suggesting an exploitable 3D-signature of cell adhesion protein binding. 24252626 3 16 theme Lewis 669:673 arg1 antennae 681:688 sialyl Lewis (sLe) antennae 662:688 sialyl Lewis (sLe) antennae 662:688 In 10μs simulations, conformational equilibria of mannosyl cores, sialyl Lewis (sLe) antennae, and constituent sub-sequences agreed with prior refinements (X-ray and NMR). 24252626 5 17 theme ring 969:972 arg1 transitions 989:999 Linkage and ring conformational transitions 957:999 Linkage and ring conformational transitions that have eluded precise quantification by experiment and conventional (ns) simulations 957:1087 Linkage and ring conformational transitions that have eluded precise quantification by experiment and conventional (ns) simulations were predicted to occur on μs timescales. 24252626 7 18 theme dynamics 1345:1352 arg1 Analyses 1326:1333 Analyses 1326:1333 Analyses of sLe(x) dynamics over 25μs 1326:1362 Analyses of sLe(x) dynamics over 25μs revealed that only 10μs were sufficient to explore all aqueous conformers. 24252626 2 19 theme model 525:529 arg1 motions 534:540 model μs motions 525:540 model μs motions in N-glycans that underpin inflammation and immunity 525:593 Toward routine prediction of oligosaccharide conformational populations and exchange rates at thermodynamic equilibrium, we apply hardware-accelerated aqueous molecular dynamics to model μs motions in N-glycans that underpin inflammation and immunity. 24252626 2 20 from equilibrium 452:462 arg1 populations 404:414 oligosaccharide conformational populations 373:414 oligosaccharide conformational populations 373:414 Toward routine prediction of oligosaccharide conformational populations and exchange rates at thermodynamic equilibrium, we apply hardware-accelerated aqueous molecular dynamics to model μs motions in N-glycans that underpin inflammation and immunity. 24252626 2 20 from equilibrium 452:462 arg1 rates 429:433 exchange rates 420:433 exchange rates at thermodynamic equilibrium 420:462 Toward routine prediction of oligosaccharide conformational populations and exchange rates at thermodynamic equilibrium, we apply hardware-accelerated aqueous molecular dynamics to model μs motions in N-glycans that underpin inflammation and immunity. 24252626 2 20 from equilibrium 452:462 arg1 prediction 359:368 routine prediction 351:368 routine prediction of oligosaccharide conformational populations and exchange rates at thermodynamic equilibrium 351:462 Toward routine prediction of oligosaccharide conformational populations and exchange rates at thermodynamic equilibrium, we apply hardware-accelerated aqueous molecular dynamics to model μs motions in N-glycans that underpin inflammation and immunity. 24252626 0 21 theme oligosaccharide 63:77 arg1 analysis 94:101 oligosaccharide conformational analysis 63:101 oligosaccharide conformational analysis applied to N-linked glycans 63:129 Shaping up for structural glycomics: a predictive protocol for oligosaccharide conformational analysis applied to N-linked glycans. 24252626 1 22 theme biomaterials 330:341 arg1 recognition 245:255 glycan recognition 238:255 glycan recognition 238:255 The human glycome comprises a vast untapped repository of 3D-structural information that holds the key to glycan recognition and a new era of rationally designed mimetic chemical probes, drugs, and biomaterials. 24252626 1 22 theme biomaterials 330:341 arg1 era 267:269 a new era 261:269 a new era of rationally designed mimetic chemical probes, drugs, and biomaterials 261:341 The human glycome comprises a vast untapped repository of 3D-structural information that holds the key to glycan recognition and a new era of rationally designed mimetic chemical probes, drugs, and biomaterials. 24252626 1 23 theme vast 162:165 arg1 repository 176:185 a vast untapped repository 160:185 a vast untapped repository of 3D-structural information that holds the key to glycan recognition and a new era of rationally designed mimetic chemical probes, drugs, and biomaterials 160:341 The human glycome comprises a vast untapped repository of 3D-structural information that holds the key to glycan recognition and a new era of rationally designed mimetic chemical probes, drugs, and biomaterials. 24252626 4 24 theme pyranose 791:798 arg1 ring 800:803 pyranose ring 791:803 pyranose ring 791:803 Glycosidic linkage and pyranose ring flexing were affected by branching, linkage position, and secondary structure, implicating sequence dependent motions in glycomic functional diversity. 24252626 5 25 theme precise 1018:1024 arg1 quantification 1026:1039 precise quantification 1018:1039 precise quantification 1018:1039 Linkage and ring conformational transitions that have eluded precise quantification by experiment and conventional (ns) simulations were predicted to occur on μs timescales. 24252626 1 26 theme human 136:140 arg1 glycome 142:148 The human glycome 132:148 The human glycome 132:148 The human glycome comprises a vast untapped repository of 3D-structural information that holds the key to glycan recognition and a new era of rationally designed mimetic chemical probes, drugs, and biomaterials. 24252626 8 27 theme 3D-structure 1535:1546 arg1 independent 1512:1522 independent 1512:1522 independent 1512:1522 This simulation protocol, which yields conformational ensembles that are independent of initial 3D-structure, is proposed as a route to understanding oligosaccharide recognition and structure-activity relationships, toward development of carbohydrate-based novel chemical entities. 24252626 1 28 theme mimetic 294:300 arg1 probes 311:316 rationally designed mimetic chemical probes 274:316 rationally designed mimetic chemical probes 274:316 The human glycome comprises a vast untapped repository of 3D-structural information that holds the key to glycan recognition and a new era of rationally designed mimetic chemical probes, drugs, and biomaterials. 24252626 2 29 theme conformational 389:402 arg1 populations 404:414 oligosaccharide conformational populations 373:414 oligosaccharide conformational populations 373:414 Toward routine prediction of oligosaccharide conformational populations and exchange rates at thermodynamic equilibrium, we apply hardware-accelerated aqueous molecular dynamics to model μs motions in N-glycans that underpin inflammation and immunity. 24252626 0 30 theme Shaping 0:6 arg1 up 8:9 Shaping up 0:9 Shaping up for structural glycomics: a predictive protocol for oligosaccharide conformational analysis applied to N-linked glycans. 0:130 Shaping up for structural glycomics: a predictive protocol for oligosaccharide conformational analysis applied to N-linked glycans. 24252626 6 31 theme sLe 1229:1231 arg1 pyranoses 1205:1213 the stacked galactose and fucose pyranoses 1172:1213 pyranoses 1205:1213 All rings populated non-chair shapes and the stacked galactose and fucose pyranoses of sLe(a) and sLe(x) were rigidified, suggesting an exploitable 3D-signature of cell adhesion protein binding. 24252626 6 31 theme sLe 1229:1231 arg1 rigidified 1241:1250 rigidified 1241:1250 rigidified 1241:1250 All rings populated non-chair shapes and the stacked galactose and fucose pyranoses of sLe(a) and sLe(x) were rigidified, suggesting an exploitable 3D-signature of cell adhesion protein binding. 24252626 6 31 theme sLe 1229:1231 arg1 galactose 1184:1192 the stacked galactose and fucose pyranoses 1172:1213 galactose 1184:1192 All rings populated non-chair shapes and the stacked galactose and fucose pyranoses of sLe(a) and sLe(x) were rigidified, suggesting an exploitable 3D-signature of cell adhesion protein binding. 24252626 2 32 theme thermodynamic 438:450 arg1 equilibrium 452:462 thermodynamic equilibrium 438:462 thermodynamic equilibrium 438:462 Toward routine prediction of oligosaccharide conformational populations and exchange rates at thermodynamic equilibrium, we apply hardware-accelerated aqueous molecular dynamics to model μs motions in N-glycans that underpin inflammation and immunity. 24252626 1 33 theme designed 285:292 arg1 probes 311:316 rationally designed mimetic chemical probes 274:316 rationally designed mimetic chemical probes 274:316 The human glycome comprises a vast untapped repository of 3D-structural information that holds the key to glycan recognition and a new era of rationally designed mimetic chemical probes, drugs, and biomaterials. 24252626 3 34 theme antennae 681:688 arg1 equilibria 632:641 conformational equilibria 617:641 conformational equilibria of mannosyl cores, sialyl Lewis (sLe) antennae, and constituent sub-sequences 617:719 In 10μs simulations, conformational equilibria of mannosyl cores, sialyl Lewis (sLe) antennae, and constituent sub-sequences agreed with prior refinements (X-ray and NMR). 24252626 4 35 theme linkage 841:847 arg1 position 849:856 linkage position 841:856 linkage position 841:856 Glycosidic linkage and pyranose ring flexing were affected by branching, linkage position, and secondary structure, implicating sequence dependent motions in glycomic functional diversity. 24252626 2 36 theme rates 429:433 arg1 prediction 359:368 routine prediction 351:368 routine prediction of oligosaccharide conformational populations and exchange rates at thermodynamic equilibrium 351:462 Toward routine prediction of oligosaccharide conformational populations and exchange rates at thermodynamic equilibrium, we apply hardware-accelerated aqueous molecular dynamics to model μs motions in N-glycans that underpin inflammation and immunity. 24252626 1 37 theme chemical 302:309 arg1 probes 311:316 rationally designed mimetic chemical probes 274:316 rationally designed mimetic chemical probes 274:316 The human glycome comprises a vast untapped repository of 3D-structural information that holds the key to glycan recognition and a new era of rationally designed mimetic chemical probes, drugs, and biomaterials. 24252626 2 38 theme aqueous 495:501 arg1 dynamics 513:520 hardware-accelerated aqueous molecular dynamics 474:520 hardware-accelerated aqueous molecular dynamics 474:520 Toward routine prediction of oligosaccharide conformational populations and exchange rates at thermodynamic equilibrium, we apply hardware-accelerated aqueous molecular dynamics to model μs motions in N-glycans that underpin inflammation and immunity. 24252626 6 39 theme stacked 1176:1182 arg1 rigidified 1241:1250 rigidified 1241:1250 rigidified 1241:1250 All rings populated non-chair shapes and the stacked galactose and fucose pyranoses of sLe(a) and sLe(x) were rigidified, suggesting an exploitable 3D-signature of cell adhesion protein binding. 24252626 6 39 theme stacked 1176:1182 arg1 galactose 1184:1192 the stacked galactose and fucose pyranoses 1172:1213 galactose 1184:1192 All rings populated non-chair shapes and the stacked galactose and fucose pyranoses of sLe(a) and sLe(x) were rigidified, suggesting an exploitable 3D-signature of cell adhesion protein binding. 24252626 3 40 theme sub-sequences 707:719 arg1 equilibria 632:641 conformational equilibria 617:641 conformational equilibria of mannosyl cores, sialyl Lewis (sLe) antennae, and constituent sub-sequences 617:719 In 10μs simulations, conformational equilibria of mannosyl cores, sialyl Lewis (sLe) antennae, and constituent sub-sequences agreed with prior refinements (X-ray and NMR). 24252626 8 41 theme chemical 1702:1709 arg1 entities 1711:1718 carbohydrate-based novel chemical entities 1677:1718 carbohydrate-based novel chemical entities 1677:1718 This simulation protocol, which yields conformational ensembles that are independent of initial 3D-structure, is proposed as a route to understanding oligosaccharide recognition and structure-activity relationships, toward development of carbohydrate-based novel chemical entities. 24252626 0 42 link N-linked 114:121 arg1 glycans 123:129 N-linked glycans 114:129 N-linked glycans 114:129 Shaping up for structural glycomics: a predictive protocol for oligosaccharide conformational analysis applied to N-linked glycans. 24252626 8 43 theme structure-activity 1621:1638 arg1 relationships 1640:1652 structure-activity relationships 1621:1652 structure-activity relationships 1621:1652 This simulation protocol, which yields conformational ensembles that are independent of initial 3D-structure, is proposed as a route to understanding oligosaccharide recognition and structure-activity relationships, toward development of carbohydrate-based novel chemical entities. 24252626 1 44 theme glycan 238:243 arg1 recognition 245:255 glycan recognition 238:255 glycan recognition 238:255 The human glycome comprises a vast untapped repository of 3D-structural information that holds the key to glycan recognition and a new era of rationally designed mimetic chemical probes, drugs, and biomaterials. 24252626 6 45 theme non-chair 1151:1159 arg1 shapes 1161:1166 non-chair shapes 1151:1166 non-chair shapes 1151:1166 All rings populated non-chair shapes and the stacked galactose and fucose pyranoses of sLe(a) and sLe(x) were rigidified, suggesting an exploitable 3D-signature of cell adhesion protein binding. 24252626 6 46 theme protein 1309:1315 arg1 binding 1317:1323 cell adhesion protein binding 1295:1323 cell adhesion protein binding 1295:1323 All rings populated non-chair shapes and the stacked galactose and fucose pyranoses of sLe(a) and sLe(x) were rigidified, suggesting an exploitable 3D-signature of cell adhesion protein binding. 24252626 2 47 theme routine 351:357 arg1 prediction 359:368 routine prediction 351:368 routine prediction of oligosaccharide conformational populations and exchange rates at thermodynamic equilibrium 351:462 Toward routine prediction of oligosaccharide conformational populations and exchange rates at thermodynamic equilibrium, we apply hardware-accelerated aqueous molecular dynamics to model μs motions in N-glycans that underpin inflammation and immunity. 24252626 6 48 theme cell 1295:1298 arg1 binding 1317:1323 cell adhesion protein binding 1295:1323 cell adhesion protein binding 1295:1323 All rings populated non-chair shapes and the stacked galactose and fucose pyranoses of sLe(a) and sLe(x) were rigidified, suggesting an exploitable 3D-signature of cell adhesion protein binding. 24252626 1 49 theme new 263:265 arg1 era 267:269 a new era 261:269 a new era of rationally designed mimetic chemical probes, drugs, and biomaterials 261:341 The human glycome comprises a vast untapped repository of 3D-structural information that holds the key to glycan recognition and a new era of rationally designed mimetic chemical probes, drugs, and biomaterials. 24252626 4 50 theme dependent 905:913 arg1 motions 915:921 sequence dependent motions 896:921 sequence dependent motions 896:921 Glycosidic linkage and pyranose ring flexing were affected by branching, linkage position, and secondary structure, implicating sequence dependent motions in glycomic functional diversity. 24252626 8 51 theme carbohydrate-based 1677:1694 arg1 entities 1711:1718 carbohydrate-based novel chemical entities 1677:1718 carbohydrate-based novel chemical entities 1677:1718 This simulation protocol, which yields conformational ensembles that are independent of initial 3D-structure, is proposed as a route to understanding oligosaccharide recognition and structure-activity relationships, toward development of carbohydrate-based novel chemical entities. 24252626 1 52 theme untapped 167:174 arg1 repository 176:185 a vast untapped repository 160:185 a vast untapped repository of 3D-structural information that holds the key to glycan recognition and a new era of rationally designed mimetic chemical probes, drugs, and biomaterials 160:341 The human glycome comprises a vast untapped repository of 3D-structural information that holds the key to glycan recognition and a new era of rationally designed mimetic chemical probes, drugs, and biomaterials. 24252626 6 53 theme sLe 1218:1220 arg1 pyranoses 1205:1213 the stacked galactose and fucose pyranoses 1172:1213 pyranoses 1205:1213 All rings populated non-chair shapes and the stacked galactose and fucose pyranoses of sLe(a) and sLe(x) were rigidified, suggesting an exploitable 3D-signature of cell adhesion protein binding. 24252626 6 53 theme sLe 1218:1220 arg1 rigidified 1241:1250 rigidified 1241:1250 rigidified 1241:1250 All rings populated non-chair shapes and the stacked galactose and fucose pyranoses of sLe(a) and sLe(x) were rigidified, suggesting an exploitable 3D-signature of cell adhesion protein binding. 24252626 6 53 theme sLe 1218:1220 arg1 galactose 1184:1192 the stacked galactose and fucose pyranoses 1172:1213 galactose 1184:1192 All rings populated non-chair shapes and the stacked galactose and fucose pyranoses of sLe(a) and sLe(x) were rigidified, suggesting an exploitable 3D-signature of cell adhesion protein binding. 24252626 1 54 theme information 204:214 arg1 repository 176:185 a vast untapped repository 160:185 a vast untapped repository of 3D-structural information that holds the key to glycan recognition and a new era of rationally designed mimetic chemical probes, drugs, and biomaterials 160:341 The human glycome comprises a vast untapped repository of 3D-structural information that holds the key to glycan recognition and a new era of rationally designed mimetic chemical probes, drugs, and biomaterials. 24252626 2 55 from motions 534:540 arg1 N-glycans 545:553 N-glycans 545:553 N-glycans that underpin inflammation and immunity 545:593 Toward routine prediction of oligosaccharide conformational populations and exchange rates at thermodynamic equilibrium, we apply hardware-accelerated aqueous molecular dynamics to model μs motions in N-glycans that underpin inflammation and immunity. 24252626 3 56 theme conformational 617:630 arg1 equilibria 632:641 conformational equilibria 617:641 conformational equilibria of mannosyl cores, sialyl Lewis (sLe) antennae, and constituent sub-sequences 617:719 In 10μs simulations, conformational equilibria of mannosyl cores, sialyl Lewis (sLe) antennae, and constituent sub-sequences agreed with prior refinements (X-ray and NMR). 24252626 4 57 dep linkage 779:785 arg1 flexing 805:811 flexing 805:811 flexing 805:811 Glycosidic linkage and pyranose ring flexing were affected by branching, linkage position, and secondary structure, implicating sequence dependent motions in glycomic functional diversity. 24252626 8 58 theme conformational 1478:1491 arg1 ensembles 1493:1501 conformational ensembles 1478:1501 conformational ensembles that are independent of initial 3D-structure 1478:1546 This simulation protocol, which yields conformational ensembles that are independent of initial 3D-structure, is proposed as a route to understanding oligosaccharide recognition and structure-activity relationships, toward development of carbohydrate-based novel chemical entities. 24252626 3 59 theme sialyl 662:667 arg1 sLe 676:678 sLe 676:678 sLe 676:678 In 10μs simulations, conformational equilibria of mannosyl cores, sialyl Lewis (sLe) antennae, and constituent sub-sequences agreed with prior refinements (X-ray and NMR). 24252626 3 59 theme sialyl 662:667 arg1 Lewis 669:673 sialyl Lewis 662:673 sialyl Lewis (sLe) antennae 662:688 In 10μs simulations, conformational equilibria of mannosyl cores, sialyl Lewis (sLe) antennae, and constituent sub-sequences agreed with prior refinements (X-ray and NMR). 24252626 4 60 theme functional 935:944 arg1 diversity 946:954 glycomic functional diversity 926:954 glycomic functional diversity 926:954 Glycosidic linkage and pyranose ring flexing were affected by branching, linkage position, and secondary structure, implicating sequence dependent motions in glycomic functional diversity. 24252626 3 61 theme cores 655:659 arg1 equilibria 632:641 conformational equilibria 617:641 conformational equilibria of mannosyl cores, sialyl Lewis (sLe) antennae, and constituent sub-sequences 617:719 In 10μs simulations, conformational equilibria of mannosyl cores, sialyl Lewis (sLe) antennae, and constituent sub-sequences agreed with prior refinements (X-ray and NMR). 24252626 2 62 theme μs 531:532 arg1 motions 534:540 model μs motions 525:540 model μs motions in N-glycans that underpin inflammation and immunity 525:593 Toward routine prediction of oligosaccharide conformational populations and exchange rates at thermodynamic equilibrium, we apply hardware-accelerated aqueous molecular dynamics to model μs motions in N-glycans that underpin inflammation and immunity. 24252626 0 63 theme conformational 79:92 arg1 analysis 94:101 oligosaccharide conformational analysis 63:101 oligosaccharide conformational analysis applied to N-linked glycans 63:129 Shaping up for structural glycomics: a predictive protocol for oligosaccharide conformational analysis applied to N-linked glycans. 24252626 8 64 theme initial 1527:1533 arg1 3D-structure 1535:1546 initial 3D-structure 1527:1546 initial 3D-structure 1527:1546 This simulation protocol, which yields conformational ensembles that are independent of initial 3D-structure, is proposed as a route to understanding oligosaccharide recognition and structure-activity relationships, toward development of carbohydrate-based novel chemical entities. 24252626 0 65 theme N-linked 114:121 arg1 glycans 123:129 N-linked glycans 114:129 N-linked glycans 114:129 Shaping up for structural glycomics: a predictive protocol for oligosaccharide conformational analysis applied to N-linked glycans. 24252626 2 66 theme populations 404:414 arg1 prediction 359:368 routine prediction 351:368 routine prediction of oligosaccharide conformational populations and exchange rates at thermodynamic equilibrium 351:462 Toward routine prediction of oligosaccharide conformational populations and exchange rates at thermodynamic equilibrium, we apply hardware-accelerated aqueous molecular dynamics to model μs motions in N-glycans that underpin inflammation and immunity. 24252626 5 67 theme conformational 974:987 arg1 transitions 989:999 Linkage and ring conformational transitions 957:999 Linkage and ring conformational transitions that have eluded precise quantification by experiment and conventional (ns) simulations 957:1087 Linkage and ring conformational transitions that have eluded precise quantification by experiment and conventional (ns) simulations were predicted to occur on μs timescales. 24252626 7 68 theme sLe 1338:1340 arg1 dynamics 1345:1352 sLe(x) dynamics 1338:1352 sLe(x) dynamics over 25μs 1338:1362 Analyses of sLe(x) dynamics over 25μs revealed that only 10μs were sufficient to explore all aqueous conformers. 24252626 2 69 theme oligosaccharide 373:387 arg1 populations 404:414 oligosaccharide conformational populations 373:414 oligosaccharide conformational populations 373:414 Toward routine prediction of oligosaccharide conformational populations and exchange rates at thermodynamic equilibrium, we apply hardware-accelerated aqueous molecular dynamics to model μs motions in N-glycans that underpin inflammation and immunity. 24252626 0 70 theme structural 15:24 arg1 glycomics 26:34 structural glycomics 15:34 structural glycomics 15:34 Shaping up for structural glycomics: a predictive protocol for oligosaccharide conformational analysis applied to N-linked glycans. 24252626 0 71 dep up 8:9 arg1 protocol 50:57 a predictive protocol 37:57 Shaping up for structural glycomics: a predictive protocol for oligosaccharide conformational analysis applied to N-linked glycans. 0:130 Shaping up for structural glycomics: a predictive protocol for oligosaccharide conformational analysis applied to N-linked glycans. 24252626 4 72 theme Glycosidic 768:777 arg1 linkage 779:785 Glycosidic linkage 768:785 Glycosidic linkage 768:785 Glycosidic linkage and pyranose ring flexing were affected by branching, linkage position, and secondary structure, implicating sequence dependent motions in glycomic functional diversity. 24252626 3 73 dep refinements 739:749 arg1 X-ray 752:756 X-ray 752:756 X-ray 752:756 In 10μs simulations, conformational equilibria of mannosyl cores, sialyl Lewis (sLe) antennae, and constituent sub-sequences agreed with prior refinements (X-ray and NMR). 24252626 3 73 dep refinements 739:749 arg1 refinements 739:749 prior refinements 733:749 prior refinements (X-ray and NMR) 733:765 In 10μs simulations, conformational equilibria of mannosyl cores, sialyl Lewis (sLe) antennae, and constituent sub-sequences agreed with prior refinements (X-ray and NMR). 24252626 3 73 dep refinements 739:749 arg1 NMR 762:764 NMR 762:764 NMR 762:764 In 10μs simulations, conformational equilibria of mannosyl cores, sialyl Lewis (sLe) antennae, and constituent sub-sequences agreed with prior refinements (X-ray and NMR). 24252626 2 74 theme molecular 503:511 arg1 dynamics 513:520 hardware-accelerated aqueous molecular dynamics 474:520 hardware-accelerated aqueous molecular dynamics 474:520 Toward routine prediction of oligosaccharide conformational populations and exchange rates at thermodynamic equilibrium, we apply hardware-accelerated aqueous molecular dynamics to model μs motions in N-glycans that underpin inflammation and immunity. 24252626 8 75 theme oligosaccharide 1589:1603 arg1 recognition 1605:1615 oligosaccharide recognition 1589:1615 oligosaccharide recognition 1589:1615 This simulation protocol, which yields conformational ensembles that are independent of initial 3D-structure, is proposed as a route to understanding oligosaccharide recognition and structure-activity relationships, toward development of carbohydrate-based novel chemical entities. 24252626 2 76 theme exchange 420:427 arg1 rates 429:433 exchange rates 420:433 exchange rates at thermodynamic equilibrium 420:462 Toward routine prediction of oligosaccharide conformational populations and exchange rates at thermodynamic equilibrium, we apply hardware-accelerated aqueous molecular dynamics to model μs motions in N-glycans that underpin inflammation and immunity. 24252626 0 77 theme predictive 39:48 arg1 protocol 50:57 a predictive protocol 37:57 Shaping up for structural glycomics: a predictive protocol for oligosaccharide conformational analysis applied to N-linked glycans. 0:130 Shaping up for structural glycomics: a predictive protocol for oligosaccharide conformational analysis applied to N-linked glycans. 24252626 1 78 theme probes 311:316 arg1 recognition 245:255 glycan recognition 238:255 glycan recognition 238:255 The human glycome comprises a vast untapped repository of 3D-structural information that holds the key to glycan recognition and a new era of rationally designed mimetic chemical probes, drugs, and biomaterials. 24252626 1 78 theme probes 311:316 arg1 era 267:269 a new era 261:269 a new era of rationally designed mimetic chemical probes, drugs, and biomaterials 261:341 The human glycome comprises a vast untapped repository of 3D-structural information that holds the key to glycan recognition and a new era of rationally designed mimetic chemical probes, drugs, and biomaterials. 24252626 2 79 theme hardware-accelerated 474:493 arg1 dynamics 513:520 hardware-accelerated aqueous molecular dynamics 474:520 hardware-accelerated aqueous molecular dynamics 474:520 Toward routine prediction of oligosaccharide conformational populations and exchange rates at thermodynamic equilibrium, we apply hardware-accelerated aqueous molecular dynamics to model μs motions in N-glycans that underpin inflammation and immunity. 24252626 3 80 theme constituent 695:705 arg1 sub-sequences 707:719 constituent sub-sequences 695:719 constituent sub-sequences 695:719 In 10μs simulations, conformational equilibria of mannosyl cores, sialyl Lewis (sLe) antennae, and constituent sub-sequences agreed with prior refinements (X-ray and NMR). 24252626 8 81 theme entities 1711:1718 arg1 development 1662:1672 development 1662:1672 development of carbohydrate-based novel chemical entities 1662:1718 This simulation protocol, which yields conformational ensembles that are independent of initial 3D-structure, is proposed as a route to understanding oligosaccharide recognition and structure-activity relationships, toward development of carbohydrate-based novel chemical entities. 24252626 1 82 theme drugs 319:323 arg1 recognition 245:255 glycan recognition 238:255 glycan recognition 238:255 The human glycome comprises a vast untapped repository of 3D-structural information that holds the key to glycan recognition and a new era of rationally designed mimetic chemical probes, drugs, and biomaterials. 24252626 1 82 theme drugs 319:323 arg1 era 267:269 a new era 261:269 a new era of rationally designed mimetic chemical probes, drugs, and biomaterials 261:341 The human glycome comprises a vast untapped repository of 3D-structural information that holds the key to glycan recognition and a new era of rationally designed mimetic chemical probes, drugs, and biomaterials. 24252626 5 83 theme experiment 1044:1053 arg1 simulations 1077:1087 experiment and conventional (ns) simulations 1044:1087 experiment and conventional (ns) simulations 1044:1087 Linkage and ring conformational transitions that have eluded precise quantification by experiment and conventional (ns) simulations were predicted to occur on μs timescales. 24252626 5 84 theme conventional 1059:1070 arg1 simulations 1077:1087 experiment and conventional (ns) simulations 1044:1087 experiment and conventional (ns) simulations 1044:1087 Linkage and ring conformational transitions that have eluded precise quantification by experiment and conventional (ns) simulations were predicted to occur on μs timescales. 24252626 3 85 theme prior 733:737 arg1 X-ray 752:756 X-ray 752:756 X-ray 752:756 In 10μs simulations, conformational equilibria of mannosyl cores, sialyl Lewis (sLe) antennae, and constituent sub-sequences agreed with prior refinements (X-ray and NMR). 24252626 3 85 theme prior 733:737 arg1 refinements 739:749 prior refinements 733:749 prior refinements (X-ray and NMR) 733:765 In 10μs simulations, conformational equilibria of mannosyl cores, sialyl Lewis (sLe) antennae, and constituent sub-sequences agreed with prior refinements (X-ray and NMR). 24252626 3 85 theme prior 733:737 arg1 NMR 762:764 NMR 762:764 NMR 762:764 In 10μs simulations, conformational equilibria of mannosyl cores, sialyl Lewis (sLe) antennae, and constituent sub-sequences agreed with prior refinements (X-ray and NMR). 29321770 11 0 theme GTP 1597:1599 arg1 level 1601:1605 intracellular GDP and GTP level 1575:1605 intracellular GDP and GTP level 1575:1605 Further analysis revealed that intracellular GDP and GTP level was decreased, and GMP level was increased in the mutant, suggesting that MoGuk2 exhibits enzymatic activity. 29321770 4 1 contain contains 619:626 arg2 acids 638:642 810 amino acids 628:642 810 amino acids 628:642 MoGuk2 contains 810 amino acids with a C-terminal GuKc domain and an additional N-terminal efThoc1 domain. 29321770 4 1 contain contains 619:626 arg1 MoGuk2 612:617 MoGuk2 612:617 MoGuk2 612:617 MoGuk2 contains 810 amino acids with a C-terminal GuKc domain and an additional N-terminal efThoc1 domain. 29321770 13 2 theme guanylate 1876:1884 arg1 important 1959:1967 important 1959:1967 important 1959:1967 Taken together, our data suggest that the guanylate kinase MoGuk2 is involved in the de novo GTP biosynthesis pathway and is important for infection-related morphogenesis in the rice blast fungus. 29321770 13 2 theme guanylate 1876:1884 arg1 MoGuk2 1893:1898 the guanylate kinase MoGuk2 1872:1898 the guanylate kinase MoGuk2 1872:1898 Taken together, our data suggest that the guanylate kinase MoGuk2 is involved in the de novo GTP biosynthesis pathway and is important for infection-related morphogenesis in the rice blast fungus. 29321770 8 3 theme ΔMoguk2 1080:1086 arg1 mutant 1088:1093 The ΔMoguk2 mutant 1076:1093 The ΔMoguk2 mutant 1076:1093 The ΔMoguk2 mutant showed weak reductions in vegetative growth, conidial germination, appressorial formation, and appressorial turgor, and showed significant reductions in sporulation and pathogenicity. 29321770 6 4 theme biological 840:849 arg1 role 851:854 the biological role 836:854 the biological role of MoGuk1 and MoGuk2 in M. oryzae 836:888 To investigate the biological role of MoGuk1 and MoGuk2 in M. oryzae, the gene replacement vectors were constructed. 29321770 8 5 theme appressorial 1162:1173 arg1 formation 1175:1183 appressorial formation 1162:1183 appressorial formation 1162:1183 The ΔMoguk2 mutant showed weak reductions in vegetative growth, conidial germination, appressorial formation, and appressorial turgor, and showed significant reductions in sporulation and pathogenicity. 29321770 1 6 from growth 269:274 arg1 yeast 350:354 yeast 350:354 yeast 350:354 Guanylate kinases (GKs), which convert guanosine monophosphate into guanosine diphosphate (GDP), are important for growth and mannose outer chain elongation of cell wall N-linked glycoproteins in yeast. 29321770 5 7 theme MoGuk2 750:755 arg1 Expression 719:728 Expression 719:728 Expression of either MoGuk1 or MoGuk2 in heterozygote yeast guk1 mutant 719:789 Expression of either MoGuk1 or MoGuk2 in heterozygote yeast guk1 mutant could increase its GDP level. 29321770 0 8 theme Blast 140:144 arg1 Fungus 146:151 the Rice Blast Fungus 131:151 the Rice Blast Fungus 131:151 The Atypical Guanylate Kinase MoGuk2 Plays Important Roles in Asexual/Sexual Development, Conidial Septation, and Pathogenicity in the Rice Blast Fungus. 29321770 11 9 theme GDP 1589:1591 arg1 level 1601:1605 intracellular GDP and GTP level 1575:1605 intracellular GDP and GTP level 1575:1605 Further analysis revealed that intracellular GDP and GTP level was decreased, and GMP level was increased in the mutant, suggesting that MoGuk2 exhibits enzymatic activity. 29321770 1 10 gly glycoproteins 333:345 arg1 glycoproteins 333:345 cell wall N-linked glycoproteins 314:345 cell wall N-linked glycoproteins in yeast 314:354 Guanylate kinases (GKs), which convert guanosine monophosphate into guanosine diphosphate (GDP), are important for growth and mannose outer chain elongation of cell wall N-linked glycoproteins in yeast. 29321770 9 11 theme neomycin-tunicamycin 1384:1403 arg1 neomycin 1358:1365 neomycin 1358:1365 neomycin 1358:1365 Moreover, the ΔMoguk2 mutant failed to produce perithecia and was sensitive to neomycin and a mixture of neomycin-tunicamycin. 29321770 9 11 theme neomycin-tunicamycin 1384:1403 arg1 mixture 1373:1379 a mixture 1371:1379 a mixture of neomycin-tunicamycin 1371:1403 Moreover, the ΔMoguk2 mutant failed to produce perithecia and was sensitive to neomycin and a mixture of neomycin-tunicamycin. 29321770 8 12 theme vegetative 1121:1130 arg1 growth 1132:1137 vegetative growth 1121:1137 vegetative growth 1121:1137 The ΔMoguk2 mutant showed weak reductions in vegetative growth, conidial germination, appressorial formation, and appressorial turgor, and showed significant reductions in sporulation and pathogenicity. 29321770 8 13 theme appressorial 1190:1201 arg1 turgor 1203:1208 appressorial turgor 1190:1208 appressorial turgor 1190:1208 The ΔMoguk2 mutant showed weak reductions in vegetative growth, conidial germination, appressorial formation, and appressorial turgor, and showed significant reductions in sporulation and pathogenicity. 29321770 5 14 theme guk1 779:782 arg1 mutant 784:789 heterozygote yeast guk1 mutant 760:789 heterozygote yeast guk1 mutant 760:789 Expression of either MoGuk1 or MoGuk2 in heterozygote yeast guk1 mutant could increase its GDP level. 29321770 2 15 theme rice 487:490 arg1 fungus 498:503 the rice blast fungus 483:503 the rice blast fungus 483:503 Here, we identified the ortholog of Saccharomyces cerevisiae GK Guk1, named MoGuk1 and a novel family of fungal GKs MoGuk2 in the rice blast fungus Magnaporthe oryzae. 29321770 0 16 from Development 77:87 arg1 Fungus 146:151 the Rice Blast Fungus 131:151 the Rice Blast Fungus 131:151 The Atypical Guanylate Kinase MoGuk2 Plays Important Roles in Asexual/Sexual Development, Conidial Septation, and Pathogenicity in the Rice Blast Fungus. 29321770 1 17 theme guanosine 193:201 arg1 monophosphate 203:215 guanosine monophosphate 193:215 guanosine monophosphate 193:215 Guanylate kinases (GKs), which convert guanosine monophosphate into guanosine diphosphate (GDP), are important for growth and mannose outer chain elongation of cell wall N-linked glycoproteins in yeast. 29321770 2 18 from family 452:457 arg1 fungus 498:503 the rice blast fungus 483:503 the rice blast fungus 483:503 Here, we identified the ortholog of Saccharomyces cerevisiae GK Guk1, named MoGuk1 and a novel family of fungal GKs MoGuk2 in the rice blast fungus Magnaporthe oryzae. 29321770 13 19 from morphogenesis 1991:2003 arg1 fungus 2023:2028 the rice blast fungus 2008:2028 the rice blast fungus 2008:2028 Taken together, our data suggest that the guanylate kinase MoGuk2 is involved in the de novo GTP biosynthesis pathway and is important for infection-related morphogenesis in the rice blast fungus. 29321770 7 20 theme ΔMoguk1 970:976 arg1 mutant 978:983 ΔMoguk1 mutant 970:983 the ΔMoguk2 but not ΔMoguk1 mutant 950:983 We obtained the ΔMoguk2 but not ΔMoguk1 mutant by screening over 1,000 transformants, indicating MoGuk1 might be essential for M. oryzae. 29321770 13 21 theme rice 2012:2015 arg1 fungus 2023:2028 the rice blast fungus 2008:2028 the rice blast fungus 2008:2028 Taken together, our data suggest that the guanylate kinase MoGuk2 is involved in the de novo GTP biosynthesis pathway and is important for infection-related morphogenesis in the rice blast fungus. 29321770 4 22 theme GuKc 662:665 arg1 domain 667:672 a C-terminal GuKc domain 649:672 a C-terminal GuKc domain 649:672 MoGuk2 contains 810 amino acids with a C-terminal GuKc domain and an additional N-terminal efThoc1 domain. 29321770 4 23 theme 810 628:630 arg1 acids 638:642 810 amino acids 628:642 810 amino acids 628:642 MoGuk2 contains 810 amino acids with a C-terminal GuKc domain and an additional N-terminal efThoc1 domain. 29321770 13 24 theme infection-related 1973:1989 arg1 morphogenesis 1991:2003 infection-related morphogenesis 1973:2003 infection-related morphogenesis in the rice blast fungus 1973:2028 Taken together, our data suggest that the guanylate kinase MoGuk2 is involved in the de novo GTP biosynthesis pathway and is important for infection-related morphogenesis in the rice blast fungus. 29321770 3 25 theme C-terminal 556:565 arg1 domain 572:577 an C-terminal GuKc domain 553:577 an C-terminal GuKc domain that very similar to yeast Guk1 553:609 MoGuk1 contains 242 aa with an C-terminal GuKc domain that very similar to yeast Guk1. 29321770 2 26 theme novel 446:450 arg1 family 452:457 a novel family 444:457 a novel family of fungal GKs MoGuk2 in the rice blast fungus 444:503 Here, we identified the ortholog of Saccharomyces cerevisiae GK Guk1, named MoGuk1 and a novel family of fungal GKs MoGuk2 in the rice blast fungus Magnaporthe oryzae. 29321770 1 27 theme cell 314:317 arg1 glycoproteins 333:345 cell wall N-linked glycoproteins 314:345 cell wall N-linked glycoproteins in yeast 314:354 Guanylate kinases (GKs), which convert guanosine monophosphate into guanosine diphosphate (GDP), are important for growth and mannose outer chain elongation of cell wall N-linked glycoproteins in yeast. 29321770 8 28 from reductions 1234:1243 arg1 sporulation 1248:1258 sporulation 1248:1258 sporulation 1248:1258 The ΔMoguk2 mutant showed weak reductions in vegetative growth, conidial germination, appressorial formation, and appressorial turgor, and showed significant reductions in sporulation and pathogenicity. 29321770 8 28 from reductions 1234:1243 arg1 pathogenicity 1264:1276 pathogenicity 1264:1276 pathogenicity 1264:1276 The ΔMoguk2 mutant showed weak reductions in vegetative growth, conidial germination, appressorial formation, and appressorial turgor, and showed significant reductions in sporulation and pathogenicity. 29321770 1 29 theme Guanylate 154:162 arg1 GKs 173:175 GKs 173:175 GKs 173:175 Guanylate kinases (GKs), which convert guanosine monophosphate into guanosine diphosphate (GDP), are important for growth and mannose outer chain elongation of cell wall N-linked glycoproteins in yeast. 29321770 1 29 theme Guanylate 154:162 arg1 kinases 164:170 Guanylate kinases 154:170 Guanylate kinases (GKs) 154:176 Guanylate kinases (GKs), which convert guanosine monophosphate into guanosine diphosphate (GDP), are important for growth and mannose outer chain elongation of cell wall N-linked glycoproteins in yeast. 29321770 10 30 from defects 1450:1456 arg1 formation 1496:1504 appressorial formation 1483:1504 appressorial formation 1483:1504 Exogenous GDP and ATP partially rescued the defects in conidial germination, appressorial formation, and infectious growth of the mutant. 29321770 10 30 from defects 1450:1456 arg1 growth 1522:1527 infectious growth 1511:1527 infectious growth 1511:1527 Exogenous GDP and ATP partially rescued the defects in conidial germination, appressorial formation, and infectious growth of the mutant. 29321770 10 30 from defects 1450:1456 arg1 germination 1470:1480 conidial germination 1461:1480 conidial germination 1461:1480 Exogenous GDP and ATP partially rescued the defects in conidial germination, appressorial formation, and infectious growth of the mutant. 29321770 4 31 theme efThoc1 703:709 arg1 domain 711:716 an additional N-terminal efThoc1 domain 678:716 an additional N-terminal efThoc1 domain 678:716 MoGuk2 contains 810 amino acids with a C-terminal GuKc domain and an additional N-terminal efThoc1 domain. 29321770 11 32 theme enzymatic 1697:1705 arg1 activity 1707:1714 enzymatic activity 1697:1714 enzymatic activity 1697:1714 Further analysis revealed that intracellular GDP and GTP level was decreased, and GMP level was increased in the mutant, suggesting that MoGuk2 exhibits enzymatic activity. 29321770 0 33 theme Conidial 90:97 arg1 Septation 99:107 Conidial Septation 90:107 Conidial Septation 90:107 The Atypical Guanylate Kinase MoGuk2 Plays Important Roles in Asexual/Sexual Development, Conidial Septation, and Pathogenicity in the Rice Blast Fungus. 29321770 1 34 theme N-linked 324:331 arg1 glycoproteins 333:345 cell wall N-linked glycoproteins 314:345 cell wall N-linked glycoproteins in yeast 314:354 Guanylate kinases (GKs), which convert guanosine monophosphate into guanosine diphosphate (GDP), are important for growth and mannose outer chain elongation of cell wall N-linked glycoproteins in yeast. 29321770 2 35 dep MoGuk1 433:438 arg1 Magnaporthe 505:515 Magnaporthe 505:515 Magnaporthe 505:515 Here, we identified the ortholog of Saccharomyces cerevisiae GK Guk1, named MoGuk1 and a novel family of fungal GKs MoGuk2 in the rice blast fungus Magnaporthe oryzae. 29321770 6 36 theme replacement 900:910 arg1 vectors 912:918 the gene replacement vectors 891:918 the gene replacement vectors 891:918 To investigate the biological role of MoGuk1 and MoGuk2 in M. oryzae, the gene replacement vectors were constructed. 29321770 2 37 theme GKs 469:471 arg1 MoGuk2 473:478 fungal GKs MoGuk2 462:478 fungal GKs MoGuk2 462:478 Here, we identified the ortholog of Saccharomyces cerevisiae GK Guk1, named MoGuk1 and a novel family of fungal GKs MoGuk2 in the rice blast fungus Magnaporthe oryzae. 29321770 2 38 dep Saccharomyces 393:405 arg1 cerevisiae 407:416 cerevisiae 407:416 cerevisiae 407:416 Here, we identified the ortholog of Saccharomyces cerevisiae GK Guk1, named MoGuk1 and a novel family of fungal GKs MoGuk2 in the rice blast fungus Magnaporthe oryzae. 29321770 2 39 theme Guk1 421:424 arg1 ortholog 381:388 the ortholog 377:388 the ortholog 377:388 Here, we identified the ortholog of Saccharomyces cerevisiae GK Guk1, named MoGuk1 and a novel family of fungal GKs MoGuk2 in the rice blast fungus Magnaporthe oryzae. 29321770 2 40 from MoGuk1 433:438 arg1 fungus 498:503 the rice blast fungus 483:503 the rice blast fungus 483:503 Here, we identified the ortholog of Saccharomyces cerevisiae GK Guk1, named MoGuk1 and a novel family of fungal GKs MoGuk2 in the rice blast fungus Magnaporthe oryzae. 29321770 10 41 theme Exogenous 1406:1414 arg1 GDP 1416:1418 Exogenous GDP 1406:1418 Exogenous GDP 1406:1418 Exogenous GDP and ATP partially rescued the defects in conidial germination, appressorial formation, and infectious growth of the mutant. 29321770 1 42 from yeast 350:354 arg1 elongation 300:309 mannose outer chain elongation 280:309 mannose outer chain elongation 280:309 Guanylate kinases (GKs), which convert guanosine monophosphate into guanosine diphosphate (GDP), are important for growth and mannose outer chain elongation of cell wall N-linked glycoproteins in yeast. 29321770 1 42 from yeast 350:354 arg1 growth 269:274 growth 269:274 growth 269:274 Guanylate kinases (GKs), which convert guanosine monophosphate into guanosine diphosphate (GDP), are important for growth and mannose outer chain elongation of cell wall N-linked glycoproteins in yeast. 29321770 12 43 theme MoGuk2 1826:1831 arg1 function 1814:1821 the full function 1805:1821 the full function of MoGuk2 1805:1831 Structural analysis proved that the efThoc1, GuKc, and P-loop domains are essential for the full function of MoGuk2. 29321770 4 44 theme additional 681:690 arg1 domain 711:716 an additional N-terminal efThoc1 domain 678:716 an additional N-terminal efThoc1 domain 678:716 MoGuk2 contains 810 amino acids with a C-terminal GuKc domain and an additional N-terminal efThoc1 domain. 29321770 0 45 theme Guanylate 13:21 arg1 MoGuk2 30:35 The Atypical Guanylate Kinase MoGuk2 0:35 The Atypical Guanylate Kinase MoGuk2 0:35 The Atypical Guanylate Kinase MoGuk2 Plays Important Roles in Asexual/Sexual Development, Conidial Septation, and Pathogenicity in the Rice Blast Fungus. 29321770 1 46 from glycoproteins 333:345 arg1 yeast 350:354 yeast 350:354 yeast 350:354 Guanylate kinases (GKs), which convert guanosine monophosphate into guanosine diphosphate (GDP), are important for growth and mannose outer chain elongation of cell wall N-linked glycoproteins in yeast. 29321770 9 47 theme ΔMoguk2 1293:1299 arg1 mutant 1301:1306 the ΔMoguk2 mutant 1289:1306 the ΔMoguk2 mutant 1289:1306 Moreover, the ΔMoguk2 mutant failed to produce perithecia and was sensitive to neomycin and a mixture of neomycin-tunicamycin. 29321770 9 47 theme ΔMoguk2 1293:1299 arg1 sensitive 1345:1353 sensitive 1345:1353 sensitive 1345:1353 Moreover, the ΔMoguk2 mutant failed to produce perithecia and was sensitive to neomycin and a mixture of neomycin-tunicamycin. 29321770 11 48 theme Further 1544:1550 arg1 analysis 1552:1559 Further analysis 1544:1559 Further analysis 1544:1559 Further analysis revealed that intracellular GDP and GTP level was decreased, and GMP level was increased in the mutant, suggesting that MoGuk2 exhibits enzymatic activity. 29321770 5 49 theme MoGuk1 740:745 arg1 Expression 719:728 Expression 719:728 Expression of either MoGuk1 or MoGuk2 in heterozygote yeast guk1 mutant 719:789 Expression of either MoGuk1 or MoGuk2 in heterozygote yeast guk1 mutant could increase its GDP level. 29321770 1 50 theme outer 288:292 arg1 elongation 300:309 mannose outer chain elongation 280:309 mannose outer chain elongation 280:309 Guanylate kinases (GKs), which convert guanosine monophosphate into guanosine diphosphate (GDP), are important for growth and mannose outer chain elongation of cell wall N-linked glycoproteins in yeast. 29321770 5 51 theme heterozygote 760:771 arg1 mutant 784:789 heterozygote yeast guk1 mutant 760:789 heterozygote yeast guk1 mutant 760:789 Expression of either MoGuk1 or MoGuk2 in heterozygote yeast guk1 mutant could increase its GDP level. 29321770 6 52 from role 851:854 arg1 oryzae 883:888 M. oryzae 880:888 M. oryzae 880:888 To investigate the biological role of MoGuk1 and MoGuk2 in M. oryzae, the gene replacement vectors were constructed. 29321770 11 53 theme intracellular 1575:1587 arg1 level 1601:1605 intracellular GDP and GTP level 1575:1605 intracellular GDP and GTP level 1575:1605 Further analysis revealed that intracellular GDP and GTP level was decreased, and GMP level was increased in the mutant, suggesting that MoGuk2 exhibits enzymatic activity. 29321770 3 54 dep similar 589:595 arg1 domain 572:577 an C-terminal GuKc domain 553:577 an C-terminal GuKc domain that very similar to yeast Guk1 553:609 MoGuk1 contains 242 aa with an C-terminal GuKc domain that very similar to yeast Guk1. 29321770 2 55 dep Magnaporthe 505:515 arg1 oryzae 517:522 Magnaporthe oryzae 505:522 Magnaporthe oryzae 505:522 Here, we identified the ortholog of Saccharomyces cerevisiae GK Guk1, named MoGuk1 and a novel family of fungal GKs MoGuk2 in the rice blast fungus Magnaporthe oryzae. 29321770 6 56 theme MoGuk1 859:864 arg1 role 851:854 the biological role 836:854 the biological role of MoGuk1 and MoGuk2 in M. oryzae 836:888 To investigate the biological role of MoGuk1 and MoGuk2 in M. oryzae, the gene replacement vectors were constructed. 29321770 0 57 from Pathogenicity 114:126 arg1 Fungus 146:151 the Rice Blast Fungus 131:151 the Rice Blast Fungus 131:151 The Atypical Guanylate Kinase MoGuk2 Plays Important Roles in Asexual/Sexual Development, Conidial Septation, and Pathogenicity in the Rice Blast Fungus. 29321770 10 58 theme appressorial 1483:1494 arg1 formation 1496:1504 appressorial formation 1483:1504 appressorial formation 1483:1504 Exogenous GDP and ATP partially rescued the defects in conidial germination, appressorial formation, and infectious growth of the mutant. 29321770 13 59 theme de 1919:1920 arg1 pathway 1944:1950 the de novo GTP biosynthesis pathway 1915:1950 the de novo GTP biosynthesis pathway 1915:1950 Taken together, our data suggest that the guanylate kinase MoGuk2 is involved in the de novo GTP biosynthesis pathway and is important for infection-related morphogenesis in the rice blast fungus. 29321770 8 60 from reductions 1107:1116 arg1 formation 1175:1183 appressorial formation 1162:1183 appressorial formation 1162:1183 The ΔMoguk2 mutant showed weak reductions in vegetative growth, conidial germination, appressorial formation, and appressorial turgor, and showed significant reductions in sporulation and pathogenicity. 29321770 8 60 from reductions 1107:1116 arg1 turgor 1203:1208 appressorial turgor 1190:1208 appressorial turgor 1190:1208 The ΔMoguk2 mutant showed weak reductions in vegetative growth, conidial germination, appressorial formation, and appressorial turgor, and showed significant reductions in sporulation and pathogenicity. 29321770 8 60 from reductions 1107:1116 arg1 growth 1132:1137 vegetative growth 1121:1137 vegetative growth 1121:1137 The ΔMoguk2 mutant showed weak reductions in vegetative growth, conidial germination, appressorial formation, and appressorial turgor, and showed significant reductions in sporulation and pathogenicity. 29321770 8 60 from reductions 1107:1116 arg1 germination 1149:1159 conidial germination 1140:1159 conidial germination 1140:1159 The ΔMoguk2 mutant showed weak reductions in vegetative growth, conidial germination, appressorial formation, and appressorial turgor, and showed significant reductions in sporulation and pathogenicity. 29321770 3 61 contain contains 532:539 arg2 aa 545:546 242 aa 541:546 242 aa 541:546 MoGuk1 contains 242 aa with an C-terminal GuKc domain that very similar to yeast Guk1. 29321770 3 61 contain contains 532:539 arg1 MoGuk1 525:530 MoGuk1 525:530 MoGuk1 525:530 MoGuk1 contains 242 aa with an C-terminal GuKc domain that very similar to yeast Guk1. 29321770 13 62 theme kinase 1886:1891 arg1 important 1959:1967 important 1959:1967 important 1959:1967 Taken together, our data suggest that the guanylate kinase MoGuk2 is involved in the de novo GTP biosynthesis pathway and is important for infection-related morphogenesis in the rice blast fungus. 29321770 13 62 theme kinase 1886:1891 arg1 MoGuk2 1893:1898 the guanylate kinase MoGuk2 1872:1898 the guanylate kinase MoGuk2 1872:1898 Taken together, our data suggest that the guanylate kinase MoGuk2 is involved in the de novo GTP biosynthesis pathway and is important for infection-related morphogenesis in the rice blast fungus. 29321770 13 63 theme GTP 1927:1929 arg1 pathway 1944:1950 the de novo GTP biosynthesis pathway 1915:1950 the de novo GTP biosynthesis pathway 1915:1950 Taken together, our data suggest that the guanylate kinase MoGuk2 is involved in the de novo GTP biosynthesis pathway and is important for infection-related morphogenesis in the rice blast fungus. 29321770 12 64 theme Structural 1717:1726 arg1 analysis 1728:1735 Structural analysis 1717:1735 Structural analysis 1717:1735 Structural analysis proved that the efThoc1, GuKc, and P-loop domains are essential for the full function of MoGuk2. 29321770 10 65 theme infectious 1511:1520 arg1 growth 1522:1527 infectious growth 1511:1527 infectious growth 1511:1527 Exogenous GDP and ATP partially rescued the defects in conidial germination, appressorial formation, and infectious growth of the mutant. 29321770 0 66 theme Important 43:51 arg1 Roles 53:57 Important Roles 43:57 Important Roles 43:57 The Atypical Guanylate Kinase MoGuk2 Plays Important Roles in Asexual/Sexual Development, Conidial Septation, and Pathogenicity in the Rice Blast Fungus. 29321770 7 67 theme 1,000 1003:1007 arg1 transformants 1009:1021 1,000 transformants 1003:1021 1,000 transformants 1003:1021 We obtained the ΔMoguk2 but not ΔMoguk1 mutant by screening over 1,000 transformants, indicating MoGuk1 might be essential for M. oryzae. 29321770 5 68 theme GDP 810:812 arg1 level 814:818 its GDP level 806:818 its GDP level 806:818 Expression of either MoGuk1 or MoGuk2 in heterozygote yeast guk1 mutant could increase its GDP level. 29321770 8 69 theme weak 1102:1105 arg1 reductions 1107:1116 weak reductions 1102:1116 weak reductions in vegetative growth, conidial germination, appressorial formation, and appressorial turgor 1102:1208 The ΔMoguk2 mutant showed weak reductions in vegetative growth, conidial germination, appressorial formation, and appressorial turgor, and showed significant reductions in sporulation and pathogenicity. 29321770 6 70 theme gene 895:898 arg1 vectors 912:918 the gene replacement vectors 891:918 the gene replacement vectors 891:918 To investigate the biological role of MoGuk1 and MoGuk2 in M. oryzae, the gene replacement vectors were constructed. 29321770 4 71 theme C-terminal 651:660 arg1 domain 667:672 a C-terminal GuKc domain 649:672 a C-terminal GuKc domain 649:672 MoGuk2 contains 810 amino acids with a C-terminal GuKc domain and an additional N-terminal efThoc1 domain. 29321770 10 72 theme mutant 1536:1541 arg1 formation 1496:1504 appressorial formation 1483:1504 appressorial formation 1483:1504 Exogenous GDP and ATP partially rescued the defects in conidial germination, appressorial formation, and infectious growth of the mutant. 29321770 10 72 theme mutant 1536:1541 arg1 growth 1522:1527 infectious growth 1511:1527 infectious growth 1511:1527 Exogenous GDP and ATP partially rescued the defects in conidial germination, appressorial formation, and infectious growth of the mutant. 29321770 10 72 theme mutant 1536:1541 arg1 germination 1470:1480 conidial germination 1461:1480 conidial germination 1461:1480 Exogenous GDP and ATP partially rescued the defects in conidial germination, appressorial formation, and infectious growth of the mutant. 29321770 5 73 theme yeast 773:777 arg1 mutant 784:789 heterozygote yeast guk1 mutant 760:789 heterozygote yeast guk1 mutant 760:789 Expression of either MoGuk1 or MoGuk2 in heterozygote yeast guk1 mutant could increase its GDP level. 29321770 2 74 theme blast 492:496 arg1 fungus 498:503 the rice blast fungus 483:503 the rice blast fungus 483:503 Here, we identified the ortholog of Saccharomyces cerevisiae GK Guk1, named MoGuk1 and a novel family of fungal GKs MoGuk2 in the rice blast fungus Magnaporthe oryzae. 29321770 0 75 theme Rice 135:138 arg1 Fungus 146:151 the Rice Blast Fungus 131:151 the Rice Blast Fungus 131:151 The Atypical Guanylate Kinase MoGuk2 Plays Important Roles in Asexual/Sexual Development, Conidial Septation, and Pathogenicity in the Rice Blast Fungus. 29321770 8 76 theme conidial 1140:1147 arg1 germination 1149:1159 conidial germination 1140:1159 conidial germination 1140:1159 The ΔMoguk2 mutant showed weak reductions in vegetative growth, conidial germination, appressorial formation, and appressorial turgor, and showed significant reductions in sporulation and pathogenicity. 29321770 6 77 theme MoGuk2 870:875 arg1 role 851:854 the biological role 836:854 the biological role of MoGuk1 and MoGuk2 in M. oryzae 836:888 To investigate the biological role of MoGuk1 and MoGuk2 in M. oryzae, the gene replacement vectors were constructed. 29321770 13 78 theme blast 2017:2021 arg1 fungus 2023:2028 the rice blast fungus 2008:2028 the rice blast fungus 2008:2028 Taken together, our data suggest that the guanylate kinase MoGuk2 is involved in the de novo GTP biosynthesis pathway and is important for infection-related morphogenesis in the rice blast fungus. 29321770 3 79 theme GuKc 567:570 arg1 domain 572:577 an C-terminal GuKc domain 553:577 an C-terminal GuKc domain that very similar to yeast Guk1 553:609 MoGuk1 contains 242 aa with an C-terminal GuKc domain that very similar to yeast Guk1. 29321770 0 80 from Septation 99:107 arg1 Fungus 146:151 the Rice Blast Fungus 131:151 the Rice Blast Fungus 131:151 The Atypical Guanylate Kinase MoGuk2 Plays Important Roles in Asexual/Sexual Development, Conidial Septation, and Pathogenicity in the Rice Blast Fungus. 29321770 8 81 theme significant 1222:1232 arg1 reductions 1234:1243 significant reductions 1222:1243 significant reductions in sporulation and pathogenicity 1222:1276 The ΔMoguk2 mutant showed weak reductions in vegetative growth, conidial germination, appressorial formation, and appressorial turgor, and showed significant reductions in sporulation and pathogenicity. 29321770 0 82 theme Asexual/Sexual 62:75 arg1 Development 77:87 Asexual/Sexual Development 62:87 Asexual/Sexual Development 62:87 The Atypical Guanylate Kinase MoGuk2 Plays Important Roles in Asexual/Sexual Development, Conidial Septation, and Pathogenicity in the Rice Blast Fungus. 29321770 4 83 theme amino 632:636 arg1 acids 638:642 810 amino acids 628:642 810 amino acids 628:642 MoGuk2 contains 810 amino acids with a C-terminal GuKc domain and an additional N-terminal efThoc1 domain. 29321770 1 84 theme wall 319:322 arg1 glycoproteins 333:345 cell wall N-linked glycoproteins 314:345 cell wall N-linked glycoproteins in yeast 314:354 Guanylate kinases (GKs), which convert guanosine monophosphate into guanosine diphosphate (GDP), are important for growth and mannose outer chain elongation of cell wall N-linked glycoproteins in yeast. 29321770 2 85 theme MoGuk2 473:478 arg1 family 452:457 a novel family 444:457 a novel family of fungal GKs MoGuk2 in the rice blast fungus 444:503 Here, we identified the ortholog of Saccharomyces cerevisiae GK Guk1, named MoGuk1 and a novel family of fungal GKs MoGuk2 in the rice blast fungus Magnaporthe oryzae. 29321770 2 85 theme MoGuk2 473:478 arg1 MoGuk1 433:438 MoGuk1 433:438 MoGuk1 433:438 Here, we identified the ortholog of Saccharomyces cerevisiae GK Guk1, named MoGuk1 and a novel family of fungal GKs MoGuk2 in the rice blast fungus Magnaporthe oryzae. 29321770 4 86 theme N-terminal 692:701 arg1 domain 711:716 an additional N-terminal efThoc1 domain 678:716 an additional N-terminal efThoc1 domain 678:716 MoGuk2 contains 810 amino acids with a C-terminal GuKc domain and an additional N-terminal efThoc1 domain. 29321770 1 87 theme glycoproteins 333:345 arg1 elongation 300:309 mannose outer chain elongation 280:309 mannose outer chain elongation 280:309 Guanylate kinases (GKs), which convert guanosine monophosphate into guanosine diphosphate (GDP), are important for growth and mannose outer chain elongation of cell wall N-linked glycoproteins in yeast. 29321770 1 87 theme glycoproteins 333:345 arg1 growth 269:274 growth 269:274 growth 269:274 Guanylate kinases (GKs), which convert guanosine monophosphate into guanosine diphosphate (GDP), are important for growth and mannose outer chain elongation of cell wall N-linked glycoproteins in yeast. 29321770 2 88 theme fungal 462:467 arg1 MoGuk2 473:478 fungal GKs MoGuk2 462:478 fungal GKs MoGuk2 462:478 Here, we identified the ortholog of Saccharomyces cerevisiae GK Guk1, named MoGuk1 and a novel family of fungal GKs MoGuk2 in the rice blast fungus Magnaporthe oryzae. 29321770 1 89 link N-linked 324:331 arg1 glycoproteins 333:345 cell wall N-linked glycoproteins 314:345 cell wall N-linked glycoproteins in yeast 314:354 Guanylate kinases (GKs), which convert guanosine monophosphate into guanosine diphosphate (GDP), are important for growth and mannose outer chain elongation of cell wall N-linked glycoproteins in yeast. 29321770 0 90 theme Atypical 4:11 arg1 MoGuk2 30:35 The Atypical Guanylate Kinase MoGuk2 0:35 The Atypical Guanylate Kinase MoGuk2 0:35 The Atypical Guanylate Kinase MoGuk2 Plays Important Roles in Asexual/Sexual Development, Conidial Septation, and Pathogenicity in the Rice Blast Fungus. 29321770 2 91 theme GK 418:419 arg1 Guk1 421:424 Saccharomyces cerevisiae GK Guk1 393:424 Saccharomyces cerevisiae GK Guk1 393:424 Here, we identified the ortholog of Saccharomyces cerevisiae GK Guk1, named MoGuk1 and a novel family of fungal GKs MoGuk2 in the rice blast fungus Magnaporthe oryzae. 29321770 0 92 theme Kinase 23:28 arg1 MoGuk2 30:35 The Atypical Guanylate Kinase MoGuk2 0:35 The Atypical Guanylate Kinase MoGuk2 0:35 The Atypical Guanylate Kinase MoGuk2 Plays Important Roles in Asexual/Sexual Development, Conidial Septation, and Pathogenicity in the Rice Blast Fungus. 29321770 13 93 dep de 1919:1920 arg1 novo 1922:1925 novo 1922:1925 novo 1922:1925 Taken together, our data suggest that the guanylate kinase MoGuk2 is involved in the de novo GTP biosynthesis pathway and is important for infection-related morphogenesis in the rice blast fungus. 29321770 2 94 theme Saccharomyces 393:405 arg1 Guk1 421:424 Saccharomyces cerevisiae GK Guk1 393:424 Saccharomyces cerevisiae GK Guk1 393:424 Here, we identified the ortholog of Saccharomyces cerevisiae GK Guk1, named MoGuk1 and a novel family of fungal GKs MoGuk2 in the rice blast fungus Magnaporthe oryzae. 29321770 12 95 theme full 1809:1812 arg1 function 1814:1821 the full function 1805:1821 the full function of MoGuk2 1805:1831 Structural analysis proved that the efThoc1, GuKc, and P-loop domains are essential for the full function of MoGuk2. 29321770 11 96 theme GMP 1626:1628 arg1 level 1630:1634 GMP level 1626:1634 GMP level 1626:1634 Further analysis revealed that intracellular GDP and GTP level was decreased, and GMP level was increased in the mutant, suggesting that MoGuk2 exhibits enzymatic activity. 29321770 1 97 theme guanosine 222:230 arg1 GDP 245:247 GDP 245:247 GDP 245:247 Guanylate kinases (GKs), which convert guanosine monophosphate into guanosine diphosphate (GDP), are important for growth and mannose outer chain elongation of cell wall N-linked glycoproteins in yeast. 29321770 1 97 theme guanosine 222:230 arg1 diphosphate 232:242 guanosine diphosphate 222:242 guanosine diphosphate (GDP) 222:248 Guanylate kinases (GKs), which convert guanosine monophosphate into guanosine diphosphate (GDP), are important for growth and mannose outer chain elongation of cell wall N-linked glycoproteins in yeast. 29321770 1 98 from elongation 300:309 arg1 yeast 350:354 yeast 350:354 yeast 350:354 Guanylate kinases (GKs), which convert guanosine monophosphate into guanosine diphosphate (GDP), are important for growth and mannose outer chain elongation of cell wall N-linked glycoproteins in yeast. 29321770 1 99 theme mannose 280:286 arg1 elongation 300:309 mannose outer chain elongation 280:309 mannose outer chain elongation 280:309 Guanylate kinases (GKs), which convert guanosine monophosphate into guanosine diphosphate (GDP), are important for growth and mannose outer chain elongation of cell wall N-linked glycoproteins in yeast. 29321770 12 100 theme P-loop 1772:1777 arg1 domains 1779:1785 the efThoc1, GuKc, and P-loop domains 1749:1785 the efThoc1, GuKc, and P-loop domains 1749:1785 Structural analysis proved that the efThoc1, GuKc, and P-loop domains are essential for the full function of MoGuk2. 29321770 12 100 theme P-loop 1772:1777 arg1 essential 1791:1799 essential 1791:1799 essential 1791:1799 Structural analysis proved that the efThoc1, GuKc, and P-loop domains are essential for the full function of MoGuk2. 29321770 12 101 theme efThoc1 1753:1759 arg1 domains 1779:1785 the efThoc1, GuKc, and P-loop domains 1749:1785 the efThoc1, GuKc, and P-loop domains 1749:1785 Structural analysis proved that the efThoc1, GuKc, and P-loop domains are essential for the full function of MoGuk2. 29321770 12 101 theme efThoc1 1753:1759 arg1 essential 1791:1799 essential 1791:1799 essential 1791:1799 Structural analysis proved that the efThoc1, GuKc, and P-loop domains are essential for the full function of MoGuk2. 29321770 10 102 theme conidial 1461:1468 arg1 germination 1470:1480 conidial germination 1461:1480 conidial germination 1461:1480 Exogenous GDP and ATP partially rescued the defects in conidial germination, appressorial formation, and infectious growth of the mutant. 29321770 13 103 theme biosynthesis 1931:1942 arg1 pathway 1944:1950 the de novo GTP biosynthesis pathway 1915:1950 the de novo GTP biosynthesis pathway 1915:1950 Taken together, our data suggest that the guanylate kinase MoGuk2 is involved in the de novo GTP biosynthesis pathway and is important for infection-related morphogenesis in the rice blast fungus. 29321770 1 104 theme chain 294:298 arg1 elongation 300:309 mannose outer chain elongation 280:309 mannose outer chain elongation 280:309 Guanylate kinases (GKs), which convert guanosine monophosphate into guanosine diphosphate (GDP), are important for growth and mannose outer chain elongation of cell wall N-linked glycoproteins in yeast. 29321770 12 105 theme GuKc 1762:1765 arg1 domains 1779:1785 the efThoc1, GuKc, and P-loop domains 1749:1785 the efThoc1, GuKc, and P-loop domains 1749:1785 Structural analysis proved that the efThoc1, GuKc, and P-loop domains are essential for the full function of MoGuk2. 29321770 12 105 theme GuKc 1762:1765 arg1 essential 1791:1799 essential 1791:1799 essential 1791:1799 Structural analysis proved that the efThoc1, GuKc, and P-loop domains are essential for the full function of MoGuk2. 29321770 3 106 theme yeast 600:604 arg1 Guk1 606:609 yeast Guk1 600:609 yeast Guk1 600:609 MoGuk1 contains 242 aa with an C-terminal GuKc domain that very similar to yeast Guk1. 29321770 5 107 from Expression 719:728 arg1 mutant 784:789 heterozygote yeast guk1 mutant 760:789 heterozygote yeast guk1 mutant 760:789 Expression of either MoGuk1 or MoGuk2 in heterozygote yeast guk1 mutant could increase its GDP level. 28752622 0 0 theme bacteria 82:89 arg1 strategies 63:72 metabolic and ecological strategies 38:72 metabolic and ecological strategies of soil bacteria 38:89 Response to nitrogen addition reveals metabolic and ecological strategies of soil bacteria. 28752622 4 1 theme given 809:813 arg1 reactions 824:832 given chemical reactions 809:832 given chemical reactions 809:832 By combining chemical, genomic and transcriptomic analysis, we are able to identify and link changes in community structure to specific organisms catalysing given chemical reactions. 28752622 6 2 from reactions 1034:1042 arg1 energy 1007:1012 energy 1007:1012 energy from N-linked redox reactions for physiological maintenance 1007:1072 This was driven by replacement of stable native populations, which utilize energy from N-linked redox reactions for physiological maintenance, with fast responding populations that use this energy for growth. 28752622 6 3 theme redox 1028:1032 arg1 reactions 1034:1042 N-linked redox reactions 1019:1042 N-linked redox reactions for physiological maintenance 1019:1072 This was driven by replacement of stable native populations, which utilize energy from N-linked redox reactions for physiological maintenance, with fast responding populations that use this energy for growth. 28752622 0 4 theme soil 77:80 arg1 bacteria 82:89 soil bacteria 77:89 soil bacteria 77:89 Response to nitrogen addition reveals metabolic and ecological strategies of soil bacteria. 28752622 3 5 theme deposition 613:622 arg1 impact 601:606 the impact 597:606 the impact of N deposition on prokaryotic communities 597:649 Here, we use soil microcosms to test the impact of N deposition on prokaryotic communities. 28752622 1 6 theme most 137:140 arg1 systems 155:161 the most well-studied systems 133:161 the most well-studied systems 133:161 The nitrogen (N) cycle represents one of the most well-studied systems, yet the taxonomic diversity of the organisms that contribute to it is mostly unknown, or linked to poorly characterized microbial groups. 28752622 2 7 theme little 479:484 arg1 connection 486:495 little connection 479:495 little connection to the role 479:507 While new information has allowed functional groups to be refined, they still rely on a priori knowledge of enzymes involved and the assumption of functional conservation, with little connection to the role the transformations, plays for specific organisms. 28752622 2 8 theme specific 540:547 arg1 organisms 549:557 specific organisms 540:557 specific organisms 540:557 While new information has allowed functional groups to be refined, they still rely on a priori knowledge of enzymes involved and the assumption of functional conservation, with little connection to the role the transformations, plays for specific organisms. 28752622 7 9 theme niche 1362:1366 arg1 differentiation 1368:1382 niche differentiation 1362:1382 niche differentiation 1362:1382 This model can be used to predict response to N disturbances and allows us to identify putative life strategies of different functional and taxonomic groups, thus providing insights into how they persist in ecosystems by niche differentiation. 28752622 5 10 from shift 900:904 arg1 composition 919:929 community composition 909:929 community composition 909:929 Urea deposition led to a decrease in prokaryotic richness, and a shift in community composition. 28752622 5 10 from shift 900:904 arg1 richness 884:891 prokaryotic richness 872:891 prokaryotic richness 872:891 Urea deposition led to a decrease in prokaryotic richness, and a shift in community composition. 28752622 5 11 theme prokaryotic 872:882 arg1 richness 884:891 prokaryotic richness 872:891 prokaryotic richness 872:891 Urea deposition led to a decrease in prokaryotic richness, and a shift in community composition. 28752622 4 12 theme chemical 815:822 arg1 reactions 824:832 given chemical reactions 809:832 given chemical reactions 809:832 By combining chemical, genomic and transcriptomic analysis, we are able to identify and link changes in community structure to specific organisms catalysing given chemical reactions. 28752622 2 13 theme new 308:310 arg1 information 312:322 new information 308:322 new information 308:322 While new information has allowed functional groups to be refined, they still rely on a priori knowledge of enzymes involved and the assumption of functional conservation, with little connection to the role the transformations, plays for specific organisms. 28752622 6 14 theme populations 980:990 arg1 replacement 951:961 replacement 951:961 replacement of stable native populations, which utilize energy from N-linked redox reactions for physiological maintenance, with fast responding populations that use this energy for growth 951:1138 This was driven by replacement of stable native populations, which utilize energy from N-linked redox reactions for physiological maintenance, with fast responding populations that use this energy for growth. 28752622 1 15 attach linked 253:258 arg1 groups 294:299 poorly characterized microbial groups 263:299 poorly characterized microbial groups 263:299 The nitrogen (N) cycle represents one of the most well-studied systems, yet the taxonomic diversity of the organisms that contribute to it is mostly unknown, or linked to poorly characterized microbial groups. 28752622 1 15 attach linked 253:258 arg2 diversity 182:190 the taxonomic diversity 168:190 the taxonomic diversity of the organisms that contribute to it 168:229 The nitrogen (N) cycle represents one of the most well-studied systems, yet the taxonomic diversity of the organisms that contribute to it is mostly unknown, or linked to poorly characterized microbial groups. 28752622 1 16 theme well-studied 142:153 arg1 systems 155:161 the most well-studied systems 133:161 the most well-studied systems 133:161 The nitrogen (N) cycle represents one of the most well-studied systems, yet the taxonomic diversity of the organisms that contribute to it is mostly unknown, or linked to poorly characterized microbial groups. 28752622 2 17 theme conservation 460:471 arg1 assumption 435:444 the assumption 431:444 the assumption of functional conservation, with little connection to the role the transformations, 431:528 While new information has allowed functional groups to be refined, they still rely on a priori knowledge of enzymes involved and the assumption of functional conservation, with little connection to the role the transformations, plays for specific organisms. 28752622 6 18 theme responding 1085:1094 arg1 populations 1096:1106 fast responding populations 1080:1106 fast responding populations that use this energy for growth 1080:1138 This was driven by replacement of stable native populations, which utilize energy from N-linked redox reactions for physiological maintenance, with fast responding populations that use this energy for growth. 28752622 5 19 from decrease 860:867 arg1 composition 919:929 community composition 909:929 community composition 909:929 Urea deposition led to a decrease in prokaryotic richness, and a shift in community composition. 28752622 5 19 from decrease 860:867 arg1 richness 884:891 prokaryotic richness 872:891 prokaryotic richness 872:891 Urea deposition led to a decrease in prokaryotic richness, and a shift in community composition. 28752622 5 20 theme community 909:917 arg1 composition 919:929 community composition 909:929 community composition 909:929 Urea deposition led to a decrease in prokaryotic richness, and a shift in community composition. 28752622 1 21 theme systems 155:161 arg1 systems 155:161 the most well-studied systems 133:161 the most well-studied systems 133:161 The nitrogen (N) cycle represents one of the most well-studied systems, yet the taxonomic diversity of the organisms that contribute to it is mostly unknown, or linked to poorly characterized microbial groups. 28752622 1 21 theme systems 155:161 arg1 one 126:128 one 126:128 one 126:128 The nitrogen (N) cycle represents one of the most well-studied systems, yet the taxonomic diversity of the organisms that contribute to it is mostly unknown, or linked to poorly characterized microbial groups. 28752622 2 22 with conservation 460:471 arg1 connection 486:495 little connection 479:495 little connection to the role 479:507 While new information has allowed functional groups to be refined, they still rely on a priori knowledge of enzymes involved and the assumption of functional conservation, with little connection to the role the transformations, plays for specific organisms. 28752622 4 23 theme genomic 675:681 arg1 analysis 702:709 chemical, genomic and transcriptomic analysis 665:709 chemical, genomic and transcriptomic analysis 665:709 By combining chemical, genomic and transcriptomic analysis, we are able to identify and link changes in community structure to specific organisms catalysing given chemical reactions. 28752622 2 24 theme priori 390:395 arg1 knowledge 397:405 a priori knowledge 388:405 a priori knowledge of enzymes involved 388:425 While new information has allowed functional groups to be refined, they still rely on a priori knowledge of enzymes involved and the assumption of functional conservation, with little connection to the role the transformations, plays for specific organisms. 28752622 4 25 theme specific 779:786 arg1 organisms 788:796 specific organisms 779:796 specific organisms catalysing given chemical reactions 779:832 By combining chemical, genomic and transcriptomic analysis, we are able to identify and link changes in community structure to specific organisms catalysing given chemical reactions. 28752622 6 26 theme fast 1080:1083 arg1 populations 1096:1106 fast responding populations 1080:1106 fast responding populations that use this energy for growth 1080:1138 This was driven by replacement of stable native populations, which utilize energy from N-linked redox reactions for physiological maintenance, with fast responding populations that use this energy for growth. 28752622 1 27 theme nitrogen 96:103 arg1 cycle 109:113 The nitrogen (N) cycle 92:113 The nitrogen (N) cycle 92:113 The nitrogen (N) cycle represents one of the most well-studied systems, yet the taxonomic diversity of the organisms that contribute to it is mostly unknown, or linked to poorly characterized microbial groups. 28752622 7 28 theme putative 1228:1235 arg1 strategies 1242:1251 putative life strategies 1228:1251 putative life strategies of different functional and taxonomic groups 1228:1296 This model can be used to predict response to N disturbances and allows us to identify putative life strategies of different functional and taxonomic groups, thus providing insights into how they persist in ecosystems by niche differentiation. 28752622 0 29 theme nitrogen 12:19 arg1 addition 21:28 nitrogen addition 12:28 nitrogen addition 12:28 Response to nitrogen addition reveals metabolic and ecological strategies of soil bacteria. 28752622 2 30 dep conservation 460:471 arg1 transformations 513:527 the transformations 509:527 the transformations 509:527 While new information has allowed functional groups to be refined, they still rely on a priori knowledge of enzymes involved and the assumption of functional conservation, with little connection to the role the transformations, plays for specific organisms. 28752622 6 31 with replacement 951:961 arg1 populations 1096:1106 fast responding populations 1080:1106 fast responding populations that use this energy for growth 1080:1138 This was driven by replacement of stable native populations, which utilize energy from N-linked redox reactions for physiological maintenance, with fast responding populations that use this energy for growth. 28752622 6 32 theme N-linked 1019:1026 arg1 reactions 1034:1042 N-linked redox reactions 1019:1042 N-linked redox reactions for physiological maintenance 1019:1072 This was driven by replacement of stable native populations, which utilize energy from N-linked redox reactions for physiological maintenance, with fast responding populations that use this energy for growth. 28752622 1 33 theme taxonomic 172:180 arg1 diversity 182:190 the taxonomic diversity 168:190 the taxonomic diversity of the organisms that contribute to it 168:229 The nitrogen (N) cycle represents one of the most well-studied systems, yet the taxonomic diversity of the organisms that contribute to it is mostly unknown, or linked to poorly characterized microbial groups. 28752622 0 34 theme metabolic 38:46 arg1 strategies 63:72 metabolic and ecological strategies 38:72 metabolic and ecological strategies of soil bacteria 38:89 Response to nitrogen addition reveals metabolic and ecological strategies of soil bacteria. 28752622 6 35 theme native 973:978 arg1 populations 980:990 stable native populations 966:990 stable native populations 966:990 This was driven by replacement of stable native populations, which utilize energy from N-linked redox reactions for physiological maintenance, with fast responding populations that use this energy for growth. 28752622 3 36 theme soil 573:576 arg1 microcosms 578:587 soil microcosms 573:587 soil microcosms 573:587 Here, we use soil microcosms to test the impact of N deposition on prokaryotic communities. 28752622 6 37 theme stable 966:971 arg1 populations 980:990 stable native populations 966:990 stable native populations 966:990 This was driven by replacement of stable native populations, which utilize energy from N-linked redox reactions for physiological maintenance, with fast responding populations that use this energy for growth. 28752622 0 38 theme ecological 52:61 arg1 strategies 63:72 metabolic and ecological strategies 38:72 metabolic and ecological strategies of soil bacteria 38:89 Response to nitrogen addition reveals metabolic and ecological strategies of soil bacteria. 28752622 3 39 from impact 601:606 arg1 communities 639:649 prokaryotic communities 627:649 prokaryotic communities 627:649 Here, we use soil microcosms to test the impact of N deposition on prokaryotic communities. 28752622 4 40 theme community 756:764 arg1 structure 766:774 community structure 756:774 community structure 756:774 By combining chemical, genomic and transcriptomic analysis, we are able to identify and link changes in community structure to specific organisms catalysing given chemical reactions. 28752622 1 41 theme N 106:106 arg1 cycle 109:113 The nitrogen (N) cycle 92:113 The nitrogen (N) cycle 92:113 The nitrogen (N) cycle represents one of the most well-studied systems, yet the taxonomic diversity of the organisms that contribute to it is mostly unknown, or linked to poorly characterized microbial groups. 28752622 1 42 theme characterized 270:282 arg1 groups 294:299 poorly characterized microbial groups 263:299 poorly characterized microbial groups 263:299 The nitrogen (N) cycle represents one of the most well-studied systems, yet the taxonomic diversity of the organisms that contribute to it is mostly unknown, or linked to poorly characterized microbial groups. 28752622 6 43 link N-linked 1019:1026 arg1 reactions 1034:1042 N-linked redox reactions 1019:1042 N-linked redox reactions for physiological maintenance 1019:1072 This was driven by replacement of stable native populations, which utilize energy from N-linked redox reactions for physiological maintenance, with fast responding populations that use this energy for growth. 28752622 4 44 from changes 745:751 arg1 structure 766:774 community structure 756:774 community structure 756:774 By combining chemical, genomic and transcriptomic analysis, we are able to identify and link changes in community structure to specific organisms catalysing given chemical reactions. 28752622 7 45 theme life 1237:1240 arg1 strategies 1242:1251 putative life strategies 1228:1251 putative life strategies of different functional and taxonomic groups 1228:1296 This model can be used to predict response to N disturbances and allows us to identify putative life strategies of different functional and taxonomic groups, thus providing insights into how they persist in ecosystems by niche differentiation. 28752622 1 46 theme microbial 284:292 arg1 groups 294:299 poorly characterized microbial groups 263:299 poorly characterized microbial groups 263:299 The nitrogen (N) cycle represents one of the most well-studied systems, yet the taxonomic diversity of the organisms that contribute to it is mostly unknown, or linked to poorly characterized microbial groups. 28752622 3 47 theme N 611:611 arg1 deposition 613:622 N deposition 611:622 N deposition 611:622 Here, we use soil microcosms to test the impact of N deposition on prokaryotic communities. 28752622 7 48 theme groups 1291:1296 arg1 strategies 1242:1251 putative life strategies 1228:1251 putative life strategies of different functional and taxonomic groups 1228:1296 This model can be used to predict response to N disturbances and allows us to identify putative life strategies of different functional and taxonomic groups, thus providing insights into how they persist in ecosystems by niche differentiation. 28752622 7 49 theme N 1187:1187 arg1 disturbances 1189:1200 N disturbances 1187:1200 N disturbances 1187:1200 This model can be used to predict response to N disturbances and allows us to identify putative life strategies of different functional and taxonomic groups, thus providing insights into how they persist in ecosystems by niche differentiation. 28752622 4 50 theme chemical 665:672 arg1 analysis 702:709 chemical, genomic and transcriptomic analysis 665:709 chemical, genomic and transcriptomic analysis 665:709 By combining chemical, genomic and transcriptomic analysis, we are able to identify and link changes in community structure to specific organisms catalysing given chemical reactions. 28752622 4 51 theme transcriptomic 687:700 arg1 analysis 702:709 chemical, genomic and transcriptomic analysis 665:709 chemical, genomic and transcriptomic analysis 665:709 By combining chemical, genomic and transcriptomic analysis, we are able to identify and link changes in community structure to specific organisms catalysing given chemical reactions. 28752622 4 52 attach link 740:743 arg1 organisms 788:796 specific organisms 779:796 specific organisms catalysing given chemical reactions 779:832 By combining chemical, genomic and transcriptomic analysis, we are able to identify and link changes in community structure to specific organisms catalysing given chemical reactions. 28752622 4 52 attach link 740:743 arg2 we 712:713 we 712:713 we 712:713 By combining chemical, genomic and transcriptomic analysis, we are able to identify and link changes in community structure to specific organisms catalysing given chemical reactions. 28752622 7 53 used used 1159:1162 arg2 model 1146:1150 This model 1141:1150 This model 1141:1150 This model can be used to predict response to N disturbances and allows us to identify putative life strategies of different functional and taxonomic groups, thus providing insights into how they persist in ecosystems by niche differentiation. 28752622 6 54 theme physiological 1048:1060 arg1 maintenance 1062:1072 physiological maintenance 1048:1072 physiological maintenance 1048:1072 This was driven by replacement of stable native populations, which utilize energy from N-linked redox reactions for physiological maintenance, with fast responding populations that use this energy for growth. 28752622 1 55 theme organisms 199:207 arg1 diversity 182:190 the taxonomic diversity 168:190 the taxonomic diversity of the organisms that contribute to it 168:229 The nitrogen (N) cycle represents one of the most well-studied systems, yet the taxonomic diversity of the organisms that contribute to it is mostly unknown, or linked to poorly characterized microbial groups. 28752622 2 56 theme functional 449:458 arg1 conservation 460:471 functional conservation 449:471 functional conservation 449:471 While new information has allowed functional groups to be refined, they still rely on a priori knowledge of enzymes involved and the assumption of functional conservation, with little connection to the role the transformations, plays for specific organisms. 28752622 2 57 theme functional 336:345 arg1 groups 347:352 functional groups 336:352 functional groups 336:352 While new information has allowed functional groups to be refined, they still rely on a priori knowledge of enzymes involved and the assumption of functional conservation, with little connection to the role the transformations, plays for specific organisms. 28752622 7 58 theme functional 1266:1275 arg1 strategies 1242:1251 putative life strategies 1228:1251 putative life strategies of different functional and taxonomic groups 1228:1296 This model can be used to predict response to N disturbances and allows us to identify putative life strategies of different functional and taxonomic groups, thus providing insights into how they persist in ecosystems by niche differentiation. 28752622 2 59 theme enzymes 410:416 arg1 knowledge 397:405 a priori knowledge 388:405 a priori knowledge of enzymes involved 388:425 While new information has allowed functional groups to be refined, they still rely on a priori knowledge of enzymes involved and the assumption of functional conservation, with little connection to the role the transformations, plays for specific organisms. 28752622 3 60 theme prokaryotic 627:637 arg1 communities 639:649 prokaryotic communities 627:649 prokaryotic communities 627:649 Here, we use soil microcosms to test the impact of N deposition on prokaryotic communities. 28752622 7 61 theme taxonomic 1281:1289 arg1 groups 1291:1296 different functional and taxonomic groups 1256:1296 groups 1291:1296 This model can be used to predict response to N disturbances and allows us to identify putative life strategies of different functional and taxonomic groups, thus providing insights into how they persist in ecosystems by niche differentiation. 28752622 5 62 theme Urea 835:838 arg1 deposition 840:849 Urea deposition 835:849 Urea deposition 835:849 Urea deposition led to a decrease in prokaryotic richness, and a shift in community composition. 27003260 0 0 theme Notch 106:110 arg1 pathway 122:128 the Notch signaling pathway 102:128 the Notch signaling pathway 102:128 Overexpression of protein O-fucosyltransferase 1 accelerates hepatocellular carcinoma progression via the Notch signaling pathway. 27003260 5 1 theme high 771:774 arg1 recurrence 784:793 high disease recurrence 771:793 high disease recurrence 771:793 We reported that Pofut1 was overexpressed in HCC cell lines and clinical HCC tissues, and Pofut1 overexpression clinically correlated with the unfavorable survival and high disease recurrence in HCC. 27003260 5 2 theme HCC 648:650 arg1 lines 657:661 HCC cell lines 648:661 HCC cell lines 648:661 We reported that Pofut1 was overexpressed in HCC cell lines and clinical HCC tissues, and Pofut1 overexpression clinically correlated with the unfavorable survival and high disease recurrence in HCC. 27003260 7 3 theme Notch 1005:1009 arg1 receptor 1011:1018 Notch receptor 1005:1018 Notch receptor 1005:1018 Furthermore, Pofut1 overexpression promoted the binding of Notch ligand Dll1 to Notch receptor, and hence activated Notch signaling pathway in HCC cells, indicating that Pofut1 overexpression could be a reason for the aberrant activation of Notch signaling in HCC. 27003260 5 4 theme unfavorable 746:756 arg1 survival 758:765 unfavorable survival 746:765 unfavorable survival 746:765 We reported that Pofut1 was overexpressed in HCC cell lines and clinical HCC tissues, and Pofut1 overexpression clinically correlated with the unfavorable survival and high disease recurrence in HCC. 27003260 4 5 theme human 584:588 arg1 tissues 594:600 253 human HCC tissues 580:600 253 human HCC tissues 580:600 In the present study, we detected the expression of Pofut1 in 8 HCC cell lines and 253 human HCC tissues. 27003260 5 6 theme disease 776:782 arg1 recurrence 784:793 high disease recurrence 771:793 high disease recurrence 771:793 We reported that Pofut1 was overexpressed in HCC cell lines and clinical HCC tissues, and Pofut1 overexpression clinically correlated with the unfavorable survival and high disease recurrence in HCC. 27003260 5 7 from recurrence 784:793 arg1 HCC 798:800 HCC 798:800 HCC 798:800 We reported that Pofut1 was overexpressed in HCC cell lines and clinical HCC tissues, and Pofut1 overexpression clinically correlated with the unfavorable survival and high disease recurrence in HCC. 27003260 5 8 theme cell 652:655 arg1 lines 657:661 HCC cell lines 648:661 HCC cell lines 648:661 We reported that Pofut1 was overexpressed in HCC cell lines and clinical HCC tissues, and Pofut1 overexpression clinically correlated with the unfavorable survival and high disease recurrence in HCC. 27003260 7 9 theme ligand 990:995 arg1 Dll1 997:1000 Notch ligand Dll1 984:1000 Notch ligand Dll1 984:1000 Furthermore, Pofut1 overexpression promoted the binding of Notch ligand Dll1 to Notch receptor, and hence activated Notch signaling pathway in HCC cells, indicating that Pofut1 overexpression could be a reason for the aberrant activation of Notch signaling in HCC. 27003260 1 10 theme liver 191:195 arg1 cancer 197:202 liver cancer 191:202 liver cancer 191:202 Aberrant activation of Notch signaling frequently occurs in liver cancer, and is associated with liver malignancies. 27003260 7 11 theme Dll1 997:1000 arg1 binding 973:979 the binding 969:979 the binding of Notch ligand Dll1 to Notch receptor 969:1018 Furthermore, Pofut1 overexpression promoted the binding of Notch ligand Dll1 to Notch receptor, and hence activated Notch signaling pathway in HCC cells, indicating that Pofut1 overexpression could be a reason for the aberrant activation of Notch signaling in HCC. 27003260 0 12 theme signaling 112:120 arg1 pathway 122:128 the Notch signaling pathway 102:128 the Notch signaling pathway 102:128 Overexpression of protein O-fucosyltransferase 1 accelerates hepatocellular carcinoma progression via the Notch signaling pathway. 27003260 4 13 theme present 504:510 arg1 study 512:516 the present study 500:516 the present study 500:516 In the present study, we detected the expression of Pofut1 in 8 HCC cell lines and 253 human HCC tissues. 27003260 6 14 theme in vitro 807:814 arg1 assay 816:820 The in vitro assay 803:820 The in vitro assay 803:820 The in vitro assay demonstrated that Pofut1 overexpression accelerated the cell proliferation and migration in HCC cells. 27003260 2 15 theme hepatocellular 314:327 arg1 HCC 340:342 HCC 340:342 HCC 340:342 However, the mechanisms regulating pathologic Notch activation in hepatocellular carcinoma (HCC) remain unclear. 27003260 2 15 theme hepatocellular 314:327 arg1 carcinoma 329:337 hepatocellular carcinoma 314:337 hepatocellular carcinoma (HCC) 314:343 However, the mechanisms regulating pathologic Notch activation in hepatocellular carcinoma (HCC) remain unclear. 27003260 4 16 theme HCC 590:592 arg1 tissues 594:600 253 human HCC tissues 580:600 253 human HCC tissues 580:600 In the present study, we detected the expression of Pofut1 in 8 HCC cell lines and 253 human HCC tissues. 27003260 6 17 theme HCC 914:916 arg1 cells 918:922 HCC cells 914:922 HCC cells 914:922 The in vitro assay demonstrated that Pofut1 overexpression accelerated the cell proliferation and migration in HCC cells. 27003260 7 18 theme Notch 984:988 arg1 Dll1 997:1000 Notch ligand Dll1 984:1000 Notch ligand Dll1 984:1000 Furthermore, Pofut1 overexpression promoted the binding of Notch ligand Dll1 to Notch receptor, and hence activated Notch signaling pathway in HCC cells, indicating that Pofut1 overexpression could be a reason for the aberrant activation of Notch signaling in HCC. 27003260 3 19 theme factor-like 467:477 arg1 repeats 479:485 the epidermal growth factor-like repeats 446:485 the epidermal growth factor-like repeats of Notch 446:494 Protein O-fucosyltransferase 1 (Pofut1) catalyzes the addition of O-linked fucose to the epidermal growth factor-like repeats of Notch. 27003260 0 20 theme hepatocellular 61:74 arg1 progression 86:96 hepatocellular carcinoma progression 61:96 hepatocellular carcinoma progression 61:96 Overexpression of protein O-fucosyltransferase 1 accelerates hepatocellular carcinoma progression via the Notch signaling pathway. 27003260 7 21 theme aberrant 1143:1150 arg1 activation 1152:1161 the aberrant activation 1139:1161 the aberrant activation of Notch signaling in HCC 1139:1187 Furthermore, Pofut1 overexpression promoted the binding of Notch ligand Dll1 to Notch receptor, and hence activated Notch signaling pathway in HCC cells, indicating that Pofut1 overexpression could be a reason for the aberrant activation of Notch signaling in HCC. 27003260 8 22 theme promising 1350:1358 arg1 blockage 1314:1321 blockage 1314:1321 blockage of this pathway 1314:1337 Taken together, our findings indicated that an aberrant activated Pofut1-Notch pathway was involved in HCC progression, and blockage of this pathway could be a promising strategy for the therapy of HCC. 27003260 8 22 theme promising 1350:1358 arg1 strategy 1360:1367 a promising strategy 1348:1367 a promising strategy for the therapy of HCC 1348:1390 Taken together, our findings indicated that an aberrant activated Pofut1-Notch pathway was involved in HCC progression, and blockage of this pathway could be a promising strategy for the therapy of HCC. 27003260 8 23 theme aberrant 1237:1244 arg1 pathway 1269:1275 an aberrant activated Pofut1-Notch pathway 1234:1275 an aberrant activated Pofut1-Notch pathway 1234:1275 Taken together, our findings indicated that an aberrant activated Pofut1-Notch pathway was involved in HCC progression, and blockage of this pathway could be a promising strategy for the therapy of HCC. 27003260 7 24 theme Pofut1 1095:1100 arg1 reason 1128:1133 a reason 1126:1133 a reason for the aberrant activation of Notch signaling in HCC 1126:1187 Furthermore, Pofut1 overexpression promoted the binding of Notch ligand Dll1 to Notch receptor, and hence activated Notch signaling pathway in HCC cells, indicating that Pofut1 overexpression could be a reason for the aberrant activation of Notch signaling in HCC. 27003260 7 24 theme Pofut1 1095:1100 arg1 overexpression 1102:1115 Pofut1 overexpression 1095:1115 Pofut1 overexpression 1095:1115 Furthermore, Pofut1 overexpression promoted the binding of Notch ligand Dll1 to Notch receptor, and hence activated Notch signaling pathway in HCC cells, indicating that Pofut1 overexpression could be a reason for the aberrant activation of Notch signaling in HCC. 27003260 7 25 theme HCC 1068:1070 arg1 cells 1072:1076 HCC cells 1068:1076 HCC cells 1068:1076 Furthermore, Pofut1 overexpression promoted the binding of Notch ligand Dll1 to Notch receptor, and hence activated Notch signaling pathway in HCC cells, indicating that Pofut1 overexpression could be a reason for the aberrant activation of Notch signaling in HCC. 27003260 3 26 theme epidermal 450:458 arg1 repeats 479:485 the epidermal growth factor-like repeats 446:485 the epidermal growth factor-like repeats of Notch 446:494 Protein O-fucosyltransferase 1 (Pofut1) catalyzes the addition of O-linked fucose to the epidermal growth factor-like repeats of Notch. 27003260 4 27 theme cell 565:568 arg1 lines 570:574 8 HCC cell lines 559:574 8 HCC cell lines 559:574 In the present study, we detected the expression of Pofut1 in 8 HCC cell lines and 253 human HCC tissues. 27003260 8 28 theme activated 1246:1254 arg1 pathway 1269:1275 an aberrant activated Pofut1-Notch pathway 1234:1275 an aberrant activated Pofut1-Notch pathway 1234:1275 Taken together, our findings indicated that an aberrant activated Pofut1-Notch pathway was involved in HCC progression, and blockage of this pathway could be a promising strategy for the therapy of HCC. 27003260 3 29 theme growth 460:465 arg1 repeats 479:485 the epidermal growth factor-like repeats 446:485 the epidermal growth factor-like repeats of Notch 446:494 Protein O-fucosyltransferase 1 (Pofut1) catalyzes the addition of O-linked fucose to the epidermal growth factor-like repeats of Notch. 27003260 0 30 theme O-fucosyltransferase 26:45 arg1 Overexpression 0:13 Overexpression 0:13 Overexpression of protein O-fucosyltransferase 1 0:47 Overexpression of protein O-fucosyltransferase 1 accelerates hepatocellular carcinoma progression via the Notch signaling pathway. 27003260 4 31 theme HCC 561:563 arg1 lines 570:574 8 HCC cell lines 559:574 8 HCC cell lines 559:574 In the present study, we detected the expression of Pofut1 in 8 HCC cell lines and 253 human HCC tissues. 27003260 8 32 theme pathway 1331:1337 arg1 blockage 1314:1321 blockage 1314:1321 blockage of this pathway 1314:1337 Taken together, our findings indicated that an aberrant activated Pofut1-Notch pathway was involved in HCC progression, and blockage of this pathway could be a promising strategy for the therapy of HCC. 27003260 8 32 theme pathway 1331:1337 arg1 strategy 1360:1367 a promising strategy 1348:1367 a promising strategy for the therapy of HCC 1348:1390 Taken together, our findings indicated that an aberrant activated Pofut1-Notch pathway was involved in HCC progression, and blockage of this pathway could be a promising strategy for the therapy of HCC. 27003260 0 33 theme protein 18:24 arg1 O-fucosyltransferase 26:45 protein O-fucosyltransferase 1 18:47 protein O-fucosyltransferase 1 18:47 Overexpression of protein O-fucosyltransferase 1 accelerates hepatocellular carcinoma progression via the Notch signaling pathway. 27003260 5 34 theme Pofut1 693:698 arg1 overexpression 700:713 Pofut1 overexpression 693:713 Pofut1 overexpression 693:713 We reported that Pofut1 was overexpressed in HCC cell lines and clinical HCC tissues, and Pofut1 overexpression clinically correlated with the unfavorable survival and high disease recurrence in HCC. 27003260 8 35 theme HCC 1388:1390 arg1 therapy 1377:1383 the therapy 1373:1383 the therapy of HCC 1373:1390 Taken together, our findings indicated that an aberrant activated Pofut1-Notch pathway was involved in HCC progression, and blockage of this pathway could be a promising strategy for the therapy of HCC. 27003260 1 36 theme Aberrant 131:138 arg1 activation 140:149 Aberrant activation 131:149 Aberrant activation of Notch signaling 131:168 Aberrant activation of Notch signaling frequently occurs in liver cancer, and is associated with liver malignancies. 27003260 5 37 dep survival 758:765 arg1 the 742:744 the 742:744 the 742:744 We reported that Pofut1 was overexpressed in HCC cell lines and clinical HCC tissues, and Pofut1 overexpression clinically correlated with the unfavorable survival and high disease recurrence in HCC. 27003260 8 38 theme HCC 1293:1295 arg1 progression 1297:1307 HCC progression 1293:1307 HCC progression 1293:1307 Taken together, our findings indicated that an aberrant activated Pofut1-Notch pathway was involved in HCC progression, and blockage of this pathway could be a promising strategy for the therapy of HCC. 27003260 3 39 link O-linked 427:434 arg1 fucose 436:441 O-linked fucose 427:441 O-linked fucose 427:441 Protein O-fucosyltransferase 1 (Pofut1) catalyzes the addition of O-linked fucose to the epidermal growth factor-like repeats of Notch. 27003260 8 40 theme Pofut1-Notch 1256:1267 arg1 pathway 1269:1275 an aberrant activated Pofut1-Notch pathway 1234:1275 an aberrant activated Pofut1-Notch pathway 1234:1275 Taken together, our findings indicated that an aberrant activated Pofut1-Notch pathway was involved in HCC progression, and blockage of this pathway could be a promising strategy for the therapy of HCC. 27003260 1 41 theme liver 228:232 arg1 malignancies 234:245 liver malignancies 228:245 liver malignancies 228:245 Aberrant activation of Notch signaling frequently occurs in liver cancer, and is associated with liver malignancies. 27003260 7 42 theme Notch 1166:1170 arg1 signaling 1172:1180 Notch signaling 1166:1180 Notch signaling 1166:1180 Furthermore, Pofut1 overexpression promoted the binding of Notch ligand Dll1 to Notch receptor, and hence activated Notch signaling pathway in HCC cells, indicating that Pofut1 overexpression could be a reason for the aberrant activation of Notch signaling in HCC. 27003260 4 43 theme Pofut1 549:554 arg1 expression 535:544 the expression 531:544 the expression of Pofut1 531:554 In the present study, we detected the expression of Pofut1 in 8 HCC cell lines and 253 human HCC tissues. 27003260 6 44 theme cell 878:881 arg1 proliferation 883:895 cell proliferation 878:895 cell proliferation 878:895 The in vitro assay demonstrated that Pofut1 overexpression accelerated the cell proliferation and migration in HCC cells. 27003260 7 45 theme signaling 1172:1180 arg1 activation 1152:1161 the aberrant activation 1139:1161 the aberrant activation of Notch signaling in HCC 1139:1187 Furthermore, Pofut1 overexpression promoted the binding of Notch ligand Dll1 to Notch receptor, and hence activated Notch signaling pathway in HCC cells, indicating that Pofut1 overexpression could be a reason for the aberrant activation of Notch signaling in HCC. 27003260 3 46 theme Notch 490:494 arg1 repeats 479:485 the epidermal growth factor-like repeats 446:485 the epidermal growth factor-like repeats of Notch 446:494 Protein O-fucosyltransferase 1 (Pofut1) catalyzes the addition of O-linked fucose to the epidermal growth factor-like repeats of Notch. 27003260 3 47 theme O-linked 427:434 arg1 fucose 436:441 O-linked fucose 427:441 O-linked fucose 427:441 Protein O-fucosyltransferase 1 (Pofut1) catalyzes the addition of O-linked fucose to the epidermal growth factor-like repeats of Notch. 27003260 5 48 theme clinical 667:674 arg1 tissues 680:686 clinical HCC tissues 667:686 clinical HCC tissues 667:686 We reported that Pofut1 was overexpressed in HCC cell lines and clinical HCC tissues, and Pofut1 overexpression clinically correlated with the unfavorable survival and high disease recurrence in HCC. 27003260 7 49 theme Notch 1041:1045 arg1 pathway 1057:1063 Notch signaling pathway 1041:1063 Notch signaling pathway 1041:1063 Furthermore, Pofut1 overexpression promoted the binding of Notch ligand Dll1 to Notch receptor, and hence activated Notch signaling pathway in HCC cells, indicating that Pofut1 overexpression could be a reason for the aberrant activation of Notch signaling in HCC. 27003260 3 50 theme fucose 436:441 arg1 addition 415:422 the addition 411:422 the addition of O-linked fucose to the epidermal growth factor-like repeats of Notch 411:494 Protein O-fucosyltransferase 1 (Pofut1) catalyzes the addition of O-linked fucose to the epidermal growth factor-like repeats of Notch. 27003260 5 51 theme HCC 676:678 arg1 tissues 680:686 clinical HCC tissues 667:686 clinical HCC tissues 667:686 We reported that Pofut1 was overexpressed in HCC cell lines and clinical HCC tissues, and Pofut1 overexpression clinically correlated with the unfavorable survival and high disease recurrence in HCC. 27003260 6 52 dep proliferation 883:895 arg1 the 874:876 the 874:876 the 874:876 The in vitro assay demonstrated that Pofut1 overexpression accelerated the cell proliferation and migration in HCC cells. 27003260 7 53 theme signaling 1047:1055 arg1 pathway 1057:1063 Notch signaling pathway 1041:1063 Notch signaling pathway 1041:1063 Furthermore, Pofut1 overexpression promoted the binding of Notch ligand Dll1 to Notch receptor, and hence activated Notch signaling pathway in HCC cells, indicating that Pofut1 overexpression could be a reason for the aberrant activation of Notch signaling in HCC. 27003260 2 54 theme Notch 294:298 arg1 activation 300:309 pathologic Notch activation 283:309 pathologic Notch activation 283:309 However, the mechanisms regulating pathologic Notch activation in hepatocellular carcinoma (HCC) remain unclear. 27003260 7 55 from activation 1152:1161 arg1 HCC 1185:1187 HCC 1185:1187 HCC 1185:1187 Furthermore, Pofut1 overexpression promoted the binding of Notch ligand Dll1 to Notch receptor, and hence activated Notch signaling pathway in HCC cells, indicating that Pofut1 overexpression could be a reason for the aberrant activation of Notch signaling in HCC. 27003260 1 56 theme Notch 154:158 arg1 signaling 160:168 Notch signaling 154:168 Notch signaling 154:168 Aberrant activation of Notch signaling frequently occurs in liver cancer, and is associated with liver malignancies. 27003260 7 57 theme Pofut1 938:943 arg1 overexpression 945:958 Pofut1 overexpression 938:958 Pofut1 overexpression 938:958 Furthermore, Pofut1 overexpression promoted the binding of Notch ligand Dll1 to Notch receptor, and hence activated Notch signaling pathway in HCC cells, indicating that Pofut1 overexpression could be a reason for the aberrant activation of Notch signaling in HCC. 27003260 5 58 from survival 758:765 arg1 HCC 798:800 HCC 798:800 HCC 798:800 We reported that Pofut1 was overexpressed in HCC cell lines and clinical HCC tissues, and Pofut1 overexpression clinically correlated with the unfavorable survival and high disease recurrence in HCC. 27003260 2 59 theme pathologic 283:292 arg1 activation 300:309 pathologic Notch activation 283:309 pathologic Notch activation 283:309 However, the mechanisms regulating pathologic Notch activation in hepatocellular carcinoma (HCC) remain unclear. 27003260 1 60 theme signaling 160:168 arg1 activation 140:149 Aberrant activation 131:149 Aberrant activation of Notch signaling 131:168 Aberrant activation of Notch signaling frequently occurs in liver cancer, and is associated with liver malignancies. 27003260 3 61 theme Protein 361:367 arg1 O-fucosyltransferase 369:388 Protein O-fucosyltransferase 1 361:390 Protein O-fucosyltransferase 1 (Pofut1) 361:399 Protein O-fucosyltransferase 1 (Pofut1) catalyzes the addition of O-linked fucose to the epidermal growth factor-like repeats of Notch. 27003260 3 61 theme Protein 361:367 arg1 Pofut1 393:398 Pofut1 393:398 Pofut1 393:398 Protein O-fucosyltransferase 1 (Pofut1) catalyzes the addition of O-linked fucose to the epidermal growth factor-like repeats of Notch. 27003260 6 62 theme Pofut1 840:845 arg1 overexpression 847:860 Pofut1 overexpression 840:860 Pofut1 overexpression 840:860 The in vitro assay demonstrated that Pofut1 overexpression accelerated the cell proliferation and migration in HCC cells. 27003260 0 63 theme carcinoma 76:84 arg1 progression 86:96 hepatocellular carcinoma progression 61:96 hepatocellular carcinoma progression 61:96 Overexpression of protein O-fucosyltransferase 1 accelerates hepatocellular carcinoma progression via the Notch signaling pathway. 27003260 6 64 from proliferation 883:895 arg1 cells 918:922 HCC cells 914:922 HCC cells 914:922 The in vitro assay demonstrated that Pofut1 overexpression accelerated the cell proliferation and migration in HCC cells. 27003260 6 65 from migration 901:909 arg1 cells 918:922 HCC cells 914:922 HCC cells 914:922 The in vitro assay demonstrated that Pofut1 overexpression accelerated the cell proliferation and migration in HCC cells. 26595890 4 0 theme dependent 570:578 arg1 mechanism 560:568 a mechanism 558:568 a mechanism dependent on viral O-linked glycans, which induce CXCR3 chemokines and stimulate antiviral activity in a manner dependent on neutrophils 558:705 The pathway is activated independently of known innate sensors of viral infections through a mechanism dependent on viral O-linked glycans, which induce CXCR3 chemokines and stimulate antiviral activity in a manner dependent on neutrophils. 26595890 5 1 theme antiviral 770:778 arg1 defense 780:786 antiviral defense 770:786 antiviral defense 770:786 This study therefore identifies a previously unknown layer of antiviral defense that exerts its action on epithelial surfaces before the classical IFN response is operative. 26595890 4 2 theme dependent 682:690 arg1 manner 675:680 a manner 673:680 a manner dependent on neutrophils 673:705 The pathway is activated independently of known innate sensors of viral infections through a mechanism dependent on viral O-linked glycans, which induce CXCR3 chemokines and stimulate antiviral activity in a manner dependent on neutrophils. 26595890 4 3 theme antiviral 651:659 arg1 activity 661:668 antiviral activity 651:668 antiviral activity in a manner dependent on neutrophils 651:705 The pathway is activated independently of known innate sensors of viral infections through a mechanism dependent on viral O-linked glycans, which induce CXCR3 chemokines and stimulate antiviral activity in a manner dependent on neutrophils. 26595890 4 4 theme viral 583:587 arg1 glycans 598:604 viral O-linked glycans 583:604 viral O-linked glycans 583:604 The pathway is activated independently of known innate sensors of viral infections through a mechanism dependent on viral O-linked glycans, which induce CXCR3 chemokines and stimulate antiviral activity in a manner dependent on neutrophils. 26595890 1 5 theme environmental 110:122 arg1 substances 124:133 environmental substances 110:133 environmental substances 110:133 Mucosal surfaces are exposed to environmental substances and represent a major portal of entry for microorganisms. 26595890 4 6 from activity 661:668 arg1 manner 675:680 a manner 673:680 a manner dependent on neutrophils 673:705 The pathway is activated independently of known innate sensors of viral infections through a mechanism dependent on viral O-linked glycans, which induce CXCR3 chemokines and stimulate antiviral activity in a manner dependent on neutrophils. 26595890 1 7 theme entry 167:171 arg1 portal 157:162 a major portal 149:162 a major portal of entry for microorganisms 149:190 Mucosal surfaces are exposed to environmental substances and represent a major portal of entry for microorganisms. 26595890 5 8 from action 804:809 arg1 surfaces 825:832 epithelial surfaces 814:832 epithelial surfaces 814:832 This study therefore identifies a previously unknown layer of antiviral defense that exerts its action on epithelial surfaces before the classical IFN response is operative. 26595890 5 9 theme defense 780:786 arg1 layer 761:765 a previously unknown layer 740:765 a previously unknown layer of antiviral defense that exerts its action on epithelial surfaces before the classical IFN response is operative 740:879 This study therefore identifies a previously unknown layer of antiviral defense that exerts its action on epithelial surfaces before the classical IFN response is operative. 26595890 1 10 theme Mucosal 78:84 arg1 surfaces 86:93 Mucosal surfaces 78:93 Mucosal surfaces 78:93 Mucosal surfaces are exposed to environmental substances and represent a major portal of entry for microorganisms. 26595890 0 11 theme innate 3:8 arg1 pathway 20:26 An innate antiviral pathway 0:26 An innate antiviral pathway 0:26 An innate antiviral pathway acting before interferons at epithelial surfaces. 26595890 4 12 theme infections 539:548 arg1 sensors 522:528 known innate sensors 509:528 known innate sensors of viral infections 509:548 The pathway is activated independently of known innate sensors of viral infections through a mechanism dependent on viral O-linked glycans, which induce CXCR3 chemokines and stimulate antiviral activity in a manner dependent on neutrophils. 26595890 5 13 theme epithelial 814:823 arg1 surfaces 825:832 epithelial surfaces 814:832 epithelial surfaces 814:832 This study therefore identifies a previously unknown layer of antiviral defense that exerts its action on epithelial surfaces before the classical IFN response is operative. 26595890 4 14 theme viral 533:537 arg1 infections 539:548 viral infections 533:548 viral infections 533:548 The pathway is activated independently of known innate sensors of viral infections through a mechanism dependent on viral O-linked glycans, which induce CXCR3 chemokines and stimulate antiviral activity in a manner dependent on neutrophils. 26595890 4 15 theme CXCR3 620:624 arg1 chemokines 626:635 CXCR3 chemokines 620:635 CXCR3 chemokines 620:635 The pathway is activated independently of known innate sensors of viral infections through a mechanism dependent on viral O-linked glycans, which induce CXCR3 chemokines and stimulate antiviral activity in a manner dependent on neutrophils. 26595890 0 16 theme antiviral 10:18 arg1 pathway 20:26 An innate antiviral pathway 0:26 An innate antiviral pathway 0:26 An innate antiviral pathway acting before interferons at epithelial surfaces. 26595890 3 17 theme innate 391:396 arg1 pathway 408:414 an innate antiviral pathway 388:414 an innate antiviral pathway that works at epithelial surfaces before the IFNs 388:464 Here we identify an innate antiviral pathway that works at epithelial surfaces before the IFNs. 26595890 5 18 theme classical 845:853 arg1 operative 871:879 operative 871:879 operative 871:879 This study therefore identifies a previously unknown layer of antiviral defense that exerts its action on epithelial surfaces before the classical IFN response is operative. 26595890 5 18 theme classical 845:853 arg1 response 859:866 the classical IFN response 841:866 the classical IFN response 841:866 This study therefore identifies a previously unknown layer of antiviral defense that exerts its action on epithelial surfaces before the classical IFN response is operative. 26595890 2 19 theme early 237:241 arg1 defense 243:249 early defense 237:249 early defense against infections 237:268 The innate immune system is responsible for early defense against infections and it is believed that the interferons (IFNs) constitute the first line of defense against viruses. 26595890 3 20 theme epithelial 430:439 arg1 surfaces 441:448 epithelial surfaces 430:448 epithelial surfaces before the IFNs 430:464 Here we identify an innate antiviral pathway that works at epithelial surfaces before the IFNs. 26595890 3 21 theme antiviral 398:406 arg1 pathway 408:414 an innate antiviral pathway 388:414 an innate antiviral pathway that works at epithelial surfaces before the IFNs 388:464 Here we identify an innate antiviral pathway that works at epithelial surfaces before the IFNs. 26595890 4 22 theme innate 515:520 arg1 sensors 522:528 known innate sensors 509:528 known innate sensors of viral infections 509:548 The pathway is activated independently of known innate sensors of viral infections through a mechanism dependent on viral O-linked glycans, which induce CXCR3 chemokines and stimulate antiviral activity in a manner dependent on neutrophils. 26595890 5 23 theme IFN 855:857 arg1 operative 871:879 operative 871:879 operative 871:879 This study therefore identifies a previously unknown layer of antiviral defense that exerts its action on epithelial surfaces before the classical IFN response is operative. 26595890 5 23 theme IFN 855:857 arg1 response 859:866 the classical IFN response 841:866 the classical IFN response 841:866 This study therefore identifies a previously unknown layer of antiviral defense that exerts its action on epithelial surfaces before the classical IFN response is operative. 26595890 4 24 theme known 509:513 arg1 sensors 522:528 known innate sensors 509:528 known innate sensors of viral infections 509:548 The pathway is activated independently of known innate sensors of viral infections through a mechanism dependent on viral O-linked glycans, which induce CXCR3 chemokines and stimulate antiviral activity in a manner dependent on neutrophils. 26595890 4 25 link O-linked 589:596 arg1 glycans 598:604 viral O-linked glycans 583:604 viral O-linked glycans 583:604 The pathway is activated independently of known innate sensors of viral infections through a mechanism dependent on viral O-linked glycans, which induce CXCR3 chemokines and stimulate antiviral activity in a manner dependent on neutrophils. 26595890 2 26 theme first 332:336 arg1 line 338:341 the first line 328:341 the first line of defense against viruses 328:368 The innate immune system is responsible for early defense against infections and it is believed that the interferons (IFNs) constitute the first line of defense against viruses. 26595890 2 27 theme immune 204:209 arg1 responsible 221:231 responsible 221:231 responsible 221:231 The innate immune system is responsible for early defense against infections and it is believed that the interferons (IFNs) constitute the first line of defense against viruses. 26595890 2 27 theme immune 204:209 arg1 system 211:216 The innate immune system 193:216 The innate immune system 193:216 The innate immune system is responsible for early defense against infections and it is believed that the interferons (IFNs) constitute the first line of defense against viruses. 26595890 2 28 theme innate 197:202 arg1 responsible 221:231 responsible 221:231 responsible 221:231 The innate immune system is responsible for early defense against infections and it is believed that the interferons (IFNs) constitute the first line of defense against viruses. 26595890 2 28 theme innate 197:202 arg1 system 211:216 The innate immune system 193:216 The innate immune system 193:216 The innate immune system is responsible for early defense against infections and it is believed that the interferons (IFNs) constitute the first line of defense against viruses. 26595890 1 29 theme major 151:155 arg1 portal 157:162 a major portal 149:162 a major portal of entry for microorganisms 149:190 Mucosal surfaces are exposed to environmental substances and represent a major portal of entry for microorganisms. 26595890 4 30 theme O-linked 589:596 arg1 glycans 598:604 viral O-linked glycans 583:604 viral O-linked glycans 583:604 The pathway is activated independently of known innate sensors of viral infections through a mechanism dependent on viral O-linked glycans, which induce CXCR3 chemokines and stimulate antiviral activity in a manner dependent on neutrophils. 26595890 5 31 theme unknown 753:759 arg1 layer 761:765 a previously unknown layer 740:765 a previously unknown layer of antiviral defense that exerts its action on epithelial surfaces before the classical IFN response is operative 740:879 This study therefore identifies a previously unknown layer of antiviral defense that exerts its action on epithelial surfaces before the classical IFN response is operative. 26595890 0 32 theme epithelial 57:66 arg1 surfaces 68:75 epithelial surfaces 57:75 epithelial surfaces 57:75 An innate antiviral pathway acting before interferons at epithelial surfaces. 26595890 2 33 theme defense 346:352 arg1 line 338:341 the first line 328:341 the first line of defense against viruses 328:368 The innate immune system is responsible for early defense against infections and it is believed that the interferons (IFNs) constitute the first line of defense against viruses. 26541755 0 0 theme human 94:98 arg1 cells 114:118 human breast cancer cells 94:118 human breast cancer cells 94:118 GalNAc-T4 putatively modulates the estrogen regulatory network through FOXA1 glycosylation in human breast cancer cells. 26541755 7 1 theme immunoprecipitation 1183:1201 arg1 assays 1203:1208 our immunoprecipitation assays 1179:1208 our immunoprecipitation assays 1179:1208 Further, our immunoprecipitation assays depicted the possibility of FOXA1 to undergo O-GalNAc modifications with a decrease of GalNAc residues in the GALNT4 knockdown cells and also impairment in the FOXA1-ERα association. 26541755 1 2 link O-linked 291:298 arg1 glycosylation 308:320 mucin-type O-linked protein glycosylation 280:320 mucin-type O-linked protein glycosylation 280:320 GALNT4 belongs to a family of N-acetylgalactosaminyltransferases, which catalyze the transfer of GalNAc to Serine or Threonine residues in the initial step of mucin-type O-linked protein glycosylation. 26541755 1 3 theme N-acetylgalactosaminyltransferases 151:184 arg1 family 141:146 a family 139:146 a family 139:146 GALNT4 belongs to a family of N-acetylgalactosaminyltransferases, which catalyze the transfer of GalNAc to Serine or Threonine residues in the initial step of mucin-type O-linked protein glycosylation. 26541755 9 4 theme estrogen 1554:1561 arg1 pathway 1563:1569 the estrogen pathway 1550:1569 the estrogen pathway through FOXA1 glycosylation 1550:1597 Together, these findings suggest a key role for GalNAc-T4 in the estrogen pathway through FOXA1 glycosylation. 26541755 2 5 theme post-translational 367:384 arg1 modification 386:397 the most complex post-translational modification 350:397 the most complex post-translational modification of proteins 350:409 This glycosylation type is the most complex post-translational modification of proteins, playing important roles during cellular differentiation and in pathological disorders. 26541755 2 5 theme post-translational 367:384 arg1 type 342:345 This glycosylation type 323:345 This glycosylation type 323:345 This glycosylation type is the most complex post-translational modification of proteins, playing important roles during cellular differentiation and in pathological disorders. 26541755 9 6 from role 1528:1531 arg1 pathway 1563:1569 the estrogen pathway 1550:1569 the estrogen pathway through FOXA1 glycosylation 1550:1597 Together, these findings suggest a key role for GalNAc-T4 in the estrogen pathway through FOXA1 glycosylation. 26541755 1 7 theme initial 264:270 arg1 step 272:275 the initial step 260:275 the initial step of mucin-type O-linked protein glycosylation 260:320 GALNT4 belongs to a family of N-acetylgalactosaminyltransferases, which catalyze the transfer of GalNAc to Serine or Threonine residues in the initial step of mucin-type O-linked protein glycosylation. 26541755 0 8 theme cancer 107:112 arg1 cells 114:118 human breast cancer cells 94:118 human breast cancer cells 94:118 GalNAc-T4 putatively modulates the estrogen regulatory network through FOXA1 glycosylation in human breast cancer cells. 26541755 5 9 theme mechanism 990:998 arg1 aspects 963:969 all the aspects 955:969 all the aspects of this regulatory mechanism 955:998 FOXA1, a key transcription factor, functions to promote estrogen responsive gene expression by acting as a cofactor to estrogen receptor alpha (ERα), but all the aspects of this regulatory mechanism are not fully explored. 26541755 8 10 theme GALNT4 1402:1407 arg1 expression 1409:1418 Rescuing GALNT4 expression 1393:1418 Rescuing GALNT4 expression 1393:1418 Rescuing GALNT4 expression could restore the interaction as well as the glycosylation of FOXA1. 26541755 4 11 theme cells 794:798 arg1 status 780:785 the estrogen status 767:785 the estrogen status of the cells 767:798 We investigated the expression of GalNAc-T4 in a panel of mammary epithelial cell lines and found its expression is associated with the estrogen status of the cells. 26541755 0 12 theme breast 100:105 arg1 cells 114:118 human breast cancer cells 94:118 human breast cancer cells 94:118 GalNAc-T4 putatively modulates the estrogen regulatory network through FOXA1 glycosylation in human breast cancer cells. 26541755 4 13 theme GalNAc-T4 669:677 arg1 expression 655:664 the expression 651:664 the expression of GalNAc-T4 in a panel of mammary epithelial cell lines 651:721 We investigated the expression of GalNAc-T4 in a panel of mammary epithelial cell lines and found its expression is associated with the estrogen status of the cells. 26541755 3 14 theme estrogen 581:588 arg1 pathway 590:596 the estrogen pathway 577:596 the estrogen pathway 577:596 Most of the breast cancer subtypes are estrogen receptor positive, and hence, the estrogen pathway represents a key regulatory network. 26541755 0 15 gly glycosylation 77:89 arg1 cells 114:118 human breast cancer cells 94:118 human breast cancer cells 94:118 GalNAc-T4 putatively modulates the estrogen regulatory network through FOXA1 glycosylation in human breast cancer cells. 26541755 7 16 theme O-GalNAc 1255:1262 arg1 modifications 1264:1276 O-GalNAc modifications 1255:1276 O-GalNAc modifications 1255:1276 Further, our immunoprecipitation assays depicted the possibility of FOXA1 to undergo O-GalNAc modifications with a decrease of GalNAc residues in the GALNT4 knockdown cells and also impairment in the FOXA1-ERα association. 26541755 5 17 theme receptor 929:936 arg1 alpha 938:942 estrogen receptor alpha 920:942 estrogen receptor alpha (ERα) 920:948 FOXA1, a key transcription factor, functions to promote estrogen responsive gene expression by acting as a cofactor to estrogen receptor alpha (ERα), but all the aspects of this regulatory mechanism are not fully explored. 26541755 5 17 theme receptor 929:936 arg1 ERα 945:947 ERα 945:947 ERα 945:947 FOXA1, a key transcription factor, functions to promote estrogen responsive gene expression by acting as a cofactor to estrogen receptor alpha (ERα), but all the aspects of this regulatory mechanism are not fully explored. 26541755 6 18 theme breast 1086:1091 arg1 cells 1100:1104 human breast cancer cells 1080:1104 human breast cancer cells 1080:1104 This study found that knockdown of GALNT4 expression in human breast cancer cells attenuated the protein expression of ERα, FOXA1, and Cyclin D1. 26541755 3 19 theme breast 511:516 arg1 subtypes 525:532 the breast cancer subtypes 507:532 the breast cancer subtypes 507:532 Most of the breast cancer subtypes are estrogen receptor positive, and hence, the estrogen pathway represents a key regulatory network. 26541755 6 20 theme GALNT4 1059:1064 arg1 expression 1066:1075 GALNT4 expression 1059:1075 GALNT4 expression in human breast cancer cells 1059:1104 This study found that knockdown of GALNT4 expression in human breast cancer cells attenuated the protein expression of ERα, FOXA1, and Cyclin D1. 26541755 4 21 theme mammary 693:699 arg1 lines 717:721 mammary epithelial cell lines 693:721 mammary epithelial cell lines 693:721 We investigated the expression of GalNAc-T4 in a panel of mammary epithelial cell lines and found its expression is associated with the estrogen status of the cells. 26541755 7 22 theme GalNAc 1297:1302 arg1 residues 1304:1311 GalNAc residues 1297:1311 GalNAc residues 1297:1311 Further, our immunoprecipitation assays depicted the possibility of FOXA1 to undergo O-GalNAc modifications with a decrease of GalNAc residues in the GALNT4 knockdown cells and also impairment in the FOXA1-ERα association. 26541755 6 23 theme human 1080:1084 arg1 cells 1100:1104 human breast cancer cells 1080:1104 human breast cancer cells 1080:1104 This study found that knockdown of GALNT4 expression in human breast cancer cells attenuated the protein expression of ERα, FOXA1, and Cyclin D1. 26541755 2 24 theme important 420:428 arg1 roles 430:434 important roles 420:434 important roles 420:434 This glycosylation type is the most complex post-translational modification of proteins, playing important roles during cellular differentiation and in pathological disorders. 26541755 6 25 theme FOXA1 1148:1152 arg1 expression 1129:1138 the protein expression 1117:1138 the protein expression of ERα, FOXA1, and Cyclin D1 1117:1167 This study found that knockdown of GALNT4 expression in human breast cancer cells attenuated the protein expression of ERα, FOXA1, and Cyclin D1. 26541755 7 26 theme FOXA1 1238:1242 arg1 possibility 1223:1233 the possibility 1219:1233 the possibility of FOXA1 to undergo O-GalNAc modifications with a decrease of GalNAc residues in the GALNT4 knockdown cells and also impairment in the FOXA1-ERα association 1219:1390 Further, our immunoprecipitation assays depicted the possibility of FOXA1 to undergo O-GalNAc modifications with a decrease of GalNAc residues in the GALNT4 knockdown cells and also impairment in the FOXA1-ERα association. 26541755 4 27 theme estrogen 771:778 arg1 status 780:785 the estrogen status 767:785 the estrogen status of the cells 767:798 We investigated the expression of GalNAc-T4 in a panel of mammary epithelial cell lines and found its expression is associated with the estrogen status of the cells. 26541755 4 28 theme cell 712:715 arg1 lines 717:721 mammary epithelial cell lines 693:721 mammary epithelial cell lines 693:721 We investigated the expression of GalNAc-T4 in a panel of mammary epithelial cell lines and found its expression is associated with the estrogen status of the cells. 26541755 1 29 theme mucin-type 280:289 arg1 glycosylation 308:320 mucin-type O-linked protein glycosylation 280:320 mucin-type O-linked protein glycosylation 280:320 GALNT4 belongs to a family of N-acetylgalactosaminyltransferases, which catalyze the transfer of GalNAc to Serine or Threonine residues in the initial step of mucin-type O-linked protein glycosylation. 26541755 6 30 from knockdown 1046:1054 arg1 cells 1100:1104 human breast cancer cells 1080:1104 human breast cancer cells 1080:1104 This study found that knockdown of GALNT4 expression in human breast cancer cells attenuated the protein expression of ERα, FOXA1, and Cyclin D1. 26541755 2 31 theme glycosylation 328:340 arg1 modification 386:397 the most complex post-translational modification 350:397 the most complex post-translational modification of proteins 350:409 This glycosylation type is the most complex post-translational modification of proteins, playing important roles during cellular differentiation and in pathological disorders. 26541755 2 31 theme glycosylation 328:340 arg1 type 342:345 This glycosylation type 323:345 This glycosylation type 323:345 This glycosylation type is the most complex post-translational modification of proteins, playing important roles during cellular differentiation and in pathological disorders. 26541755 7 32 from impairment 1352:1361 arg1 association 1380:1390 the FOXA1-ERα association 1366:1390 the FOXA1-ERα association 1366:1390 Further, our immunoprecipitation assays depicted the possibility of FOXA1 to undergo O-GalNAc modifications with a decrease of GalNAc residues in the GALNT4 knockdown cells and also impairment in the FOXA1-ERα association. 26541755 7 32 from impairment 1352:1361 arg1 cells 1337:1341 the GALNT4 knockdown cells 1316:1341 the GALNT4 knockdown cells 1316:1341 Further, our immunoprecipitation assays depicted the possibility of FOXA1 to undergo O-GalNAc modifications with a decrease of GalNAc residues in the GALNT4 knockdown cells and also impairment in the FOXA1-ERα association. 26541755 4 33 theme epithelial 701:710 arg1 lines 717:721 mammary epithelial cell lines 693:721 mammary epithelial cell lines 693:721 We investigated the expression of GalNAc-T4 in a panel of mammary epithelial cell lines and found its expression is associated with the estrogen status of the cells. 26541755 2 34 theme pathological 475:486 arg1 disorders 488:496 pathological disorders 475:496 pathological disorders 475:496 This glycosylation type is the most complex post-translational modification of proteins, playing important roles during cellular differentiation and in pathological disorders. 26541755 1 35 theme O-linked 291:298 arg1 glycosylation 308:320 mucin-type O-linked protein glycosylation 280:320 mucin-type O-linked protein glycosylation 280:320 GALNT4 belongs to a family of N-acetylgalactosaminyltransferases, which catalyze the transfer of GalNAc to Serine or Threonine residues in the initial step of mucin-type O-linked protein glycosylation. 26541755 6 36 from expression 1066:1075 arg1 cells 1100:1104 human breast cancer cells 1080:1104 human breast cancer cells 1080:1104 This study found that knockdown of GALNT4 expression in human breast cancer cells attenuated the protein expression of ERα, FOXA1, and Cyclin D1. 26541755 6 37 theme ERα 1143:1145 arg1 expression 1129:1138 the protein expression 1117:1138 the protein expression of ERα, FOXA1, and Cyclin D1 1117:1167 This study found that knockdown of GALNT4 expression in human breast cancer cells attenuated the protein expression of ERα, FOXA1, and Cyclin D1. 26541755 3 38 theme key 611:613 arg1 network 626:632 a key regulatory network 609:632 a key regulatory network 609:632 Most of the breast cancer subtypes are estrogen receptor positive, and hence, the estrogen pathway represents a key regulatory network. 26541755 1 39 theme protein 300:306 arg1 glycosylation 308:320 mucin-type O-linked protein glycosylation 280:320 mucin-type O-linked protein glycosylation 280:320 GALNT4 belongs to a family of N-acetylgalactosaminyltransferases, which catalyze the transfer of GalNAc to Serine or Threonine residues in the initial step of mucin-type O-linked protein glycosylation. 26541755 6 40 theme D1 1166:1167 arg1 expression 1129:1138 the protein expression 1117:1138 the protein expression of ERα, FOXA1, and Cyclin D1 1117:1167 This study found that knockdown of GALNT4 expression in human breast cancer cells attenuated the protein expression of ERα, FOXA1, and Cyclin D1. 26541755 5 41 theme estrogen 920:927 arg1 alpha 938:942 estrogen receptor alpha 920:942 estrogen receptor alpha (ERα) 920:948 FOXA1, a key transcription factor, functions to promote estrogen responsive gene expression by acting as a cofactor to estrogen receptor alpha (ERα), but all the aspects of this regulatory mechanism are not fully explored. 26541755 5 41 theme estrogen 920:927 arg1 ERα 945:947 ERα 945:947 ERα 945:947 FOXA1, a key transcription factor, functions to promote estrogen responsive gene expression by acting as a cofactor to estrogen receptor alpha (ERα), but all the aspects of this regulatory mechanism are not fully explored. 26541755 9 42 theme key 1524:1526 arg1 role 1528:1531 a key role 1522:1531 a key role for GalNAc-T4 in the estrogen pathway through FOXA1 glycosylation 1522:1597 Together, these findings suggest a key role for GalNAc-T4 in the estrogen pathway through FOXA1 glycosylation. 26541755 1 43 theme GalNAc 218:223 arg1 transfer 206:213 the transfer 202:213 the transfer of GalNAc to Serine or Threonine residues 202:255 GALNT4 belongs to a family of N-acetylgalactosaminyltransferases, which catalyze the transfer of GalNAc to Serine or Threonine residues in the initial step of mucin-type O-linked protein glycosylation. 26541755 0 44 theme regulatory 44:53 arg1 network 55:61 the estrogen regulatory network 31:61 the estrogen regulatory network 31:61 GalNAc-T4 putatively modulates the estrogen regulatory network through FOXA1 glycosylation in human breast cancer cells. 26541755 1 45 theme glycosylation 308:320 arg1 step 272:275 the initial step 260:275 the initial step of mucin-type O-linked protein glycosylation 260:320 GALNT4 belongs to a family of N-acetylgalactosaminyltransferases, which catalyze the transfer of GalNAc to Serine or Threonine residues in the initial step of mucin-type O-linked protein glycosylation. 26541755 5 46 theme responsive 866:875 arg1 expression 882:891 estrogen responsive gene expression 857:891 estrogen responsive gene expression 857:891 FOXA1, a key transcription factor, functions to promote estrogen responsive gene expression by acting as a cofactor to estrogen receptor alpha (ERα), but all the aspects of this regulatory mechanism are not fully explored. 26541755 9 47 theme FOXA1 1579:1583 arg1 glycosylation 1585:1597 FOXA1 glycosylation 1579:1597 FOXA1 glycosylation 1579:1597 Together, these findings suggest a key role for GalNAc-T4 in the estrogen pathway through FOXA1 glycosylation. 26541755 2 48 theme cellular 443:450 arg1 differentiation 452:466 cellular differentiation 443:466 cellular differentiation 443:466 This glycosylation type is the most complex post-translational modification of proteins, playing important roles during cellular differentiation and in pathological disorders. 26541755 0 49 theme estrogen 35:42 arg1 network 55:61 the estrogen regulatory network 31:61 the estrogen regulatory network 31:61 GalNAc-T4 putatively modulates the estrogen regulatory network through FOXA1 glycosylation in human breast cancer cells. 26541755 0 50 from glycosylation 77:89 arg1 cells 114:118 human breast cancer cells 94:118 human breast cancer cells 94:118 GalNAc-T4 putatively modulates the estrogen regulatory network through FOXA1 glycosylation in human breast cancer cells. 26541755 7 51 theme FOXA1-ERα 1370:1378 arg1 association 1380:1390 the FOXA1-ERα association 1366:1390 the FOXA1-ERα association 1366:1390 Further, our immunoprecipitation assays depicted the possibility of FOXA1 to undergo O-GalNAc modifications with a decrease of GalNAc residues in the GALNT4 knockdown cells and also impairment in the FOXA1-ERα association. 26541755 5 52 theme gene 877:880 arg1 expression 882:891 estrogen responsive gene expression 857:891 estrogen responsive gene expression 857:891 FOXA1, a key transcription factor, functions to promote estrogen responsive gene expression by acting as a cofactor to estrogen receptor alpha (ERα), but all the aspects of this regulatory mechanism are not fully explored. 26541755 5 53 theme key 810:812 arg1 factor 828:833 a key transcription factor 808:833 a key transcription factor 808:833 FOXA1, a key transcription factor, functions to promote estrogen responsive gene expression by acting as a cofactor to estrogen receptor alpha (ERα), but all the aspects of this regulatory mechanism are not fully explored. 26541755 5 53 theme key 810:812 arg1 FOXA1 801:805 FOXA1 801:805 FOXA1 801:805 FOXA1, a key transcription factor, functions to promote estrogen responsive gene expression by acting as a cofactor to estrogen receptor alpha (ERα), but all the aspects of this regulatory mechanism are not fully explored. 26541755 4 54 from expression 655:664 arg1 panel 684:688 a panel 682:688 a panel of mammary epithelial cell lines 682:721 We investigated the expression of GalNAc-T4 in a panel of mammary epithelial cell lines and found its expression is associated with the estrogen status of the cells. 26541755 3 55 theme regulatory 615:624 arg1 network 626:632 a key regulatory network 609:632 a key regulatory network 609:632 Most of the breast cancer subtypes are estrogen receptor positive, and hence, the estrogen pathway represents a key regulatory network. 26541755 7 56 from decrease 1285:1292 arg1 association 1380:1390 the FOXA1-ERα association 1366:1390 the FOXA1-ERα association 1366:1390 Further, our immunoprecipitation assays depicted the possibility of FOXA1 to undergo O-GalNAc modifications with a decrease of GalNAc residues in the GALNT4 knockdown cells and also impairment in the FOXA1-ERα association. 26541755 7 56 from decrease 1285:1292 arg1 cells 1337:1341 the GALNT4 knockdown cells 1316:1341 the GALNT4 knockdown cells 1316:1341 Further, our immunoprecipitation assays depicted the possibility of FOXA1 to undergo O-GalNAc modifications with a decrease of GalNAc residues in the GALNT4 knockdown cells and also impairment in the FOXA1-ERα association. 26541755 2 57 theme complex 359:365 arg1 modification 386:397 the most complex post-translational modification 350:397 the most complex post-translational modification of proteins 350:409 This glycosylation type is the most complex post-translational modification of proteins, playing important roles during cellular differentiation and in pathological disorders. 26541755 2 57 theme complex 359:365 arg1 type 342:345 This glycosylation type 323:345 This glycosylation type 323:345 This glycosylation type is the most complex post-translational modification of proteins, playing important roles during cellular differentiation and in pathological disorders. 26541755 5 58 theme transcription 814:826 arg1 factor 828:833 a key transcription factor 808:833 a key transcription factor 808:833 FOXA1, a key transcription factor, functions to promote estrogen responsive gene expression by acting as a cofactor to estrogen receptor alpha (ERα), but all the aspects of this regulatory mechanism are not fully explored. 26541755 5 58 theme transcription 814:826 arg1 FOXA1 801:805 FOXA1 801:805 FOXA1 801:805 FOXA1, a key transcription factor, functions to promote estrogen responsive gene expression by acting as a cofactor to estrogen receptor alpha (ERα), but all the aspects of this regulatory mechanism are not fully explored. 26541755 6 59 theme Cyclin 1159:1164 arg1 D1 1166:1167 Cyclin D1 1159:1167 Cyclin D1 1159:1167 This study found that knockdown of GALNT4 expression in human breast cancer cells attenuated the protein expression of ERα, FOXA1, and Cyclin D1. 26541755 8 60 theme Rescuing 1393:1400 arg1 expression 1409:1418 Rescuing GALNT4 expression 1393:1418 Rescuing GALNT4 expression 1393:1418 Rescuing GALNT4 expression could restore the interaction as well as the glycosylation of FOXA1. 26541755 7 61 theme GALNT4 1320:1325 arg1 cells 1337:1341 the GALNT4 knockdown cells 1316:1341 the GALNT4 knockdown cells 1316:1341 Further, our immunoprecipitation assays depicted the possibility of FOXA1 to undergo O-GalNAc modifications with a decrease of GalNAc residues in the GALNT4 knockdown cells and also impairment in the FOXA1-ERα association. 26541755 6 62 theme protein 1121:1127 arg1 expression 1129:1138 the protein expression 1117:1138 the protein expression of ERα, FOXA1, and Cyclin D1 1117:1167 This study found that knockdown of GALNT4 expression in human breast cancer cells attenuated the protein expression of ERα, FOXA1, and Cyclin D1. 26541755 5 63 theme regulatory 979:988 arg1 mechanism 990:998 this regulatory mechanism 974:998 this regulatory mechanism 974:998 FOXA1, a key transcription factor, functions to promote estrogen responsive gene expression by acting as a cofactor to estrogen receptor alpha (ERα), but all the aspects of this regulatory mechanism are not fully explored. 26541755 3 64 theme cancer 518:523 arg1 subtypes 525:532 the breast cancer subtypes 507:532 the breast cancer subtypes 507:532 Most of the breast cancer subtypes are estrogen receptor positive, and hence, the estrogen pathway represents a key regulatory network. 26541755 8 65 theme FOXA1 1482:1486 arg1 glycosylation 1465:1477 the glycosylation 1461:1477 the glycosylation of FOXA1 1461:1486 Rescuing GALNT4 expression could restore the interaction as well as the glycosylation of FOXA1. 26541755 1 66 dep Serine 228:233 arg1 residues 248:255 residues 248:255 residues 248:255 GALNT4 belongs to a family of N-acetylgalactosaminyltransferases, which catalyze the transfer of GalNAc to Serine or Threonine residues in the initial step of mucin-type O-linked protein glycosylation. 26541755 8 67 gly glycosylation 1465:1477 arg1 FOXA1 1482:1486 FOXA1 1482:1486 FOXA1 1482:1486 Rescuing GALNT4 expression could restore the interaction as well as the glycosylation of FOXA1. 26541755 6 68 theme cancer 1093:1098 arg1 cells 1100:1104 human breast cancer cells 1080:1104 human breast cancer cells 1080:1104 This study found that knockdown of GALNT4 expression in human breast cancer cells attenuated the protein expression of ERα, FOXA1, and Cyclin D1. 26541755 7 69 theme residues 1304:1311 arg1 decrease 1285:1292 a decrease 1283:1292 a decrease of GalNAc residues in the GALNT4 knockdown cells 1283:1341 Further, our immunoprecipitation assays depicted the possibility of FOXA1 to undergo O-GalNAc modifications with a decrease of GalNAc residues in the GALNT4 knockdown cells and also impairment in the FOXA1-ERα association. 26541755 7 69 theme residues 1304:1311 arg1 impairment 1352:1361 impairment 1352:1361 impairment in the FOXA1-ERα association 1352:1390 Further, our immunoprecipitation assays depicted the possibility of FOXA1 to undergo O-GalNAc modifications with a decrease of GalNAc residues in the GALNT4 knockdown cells and also impairment in the FOXA1-ERα association. 26541755 7 70 theme knockdown 1327:1335 arg1 cells 1337:1341 the GALNT4 knockdown cells 1316:1341 the GALNT4 knockdown cells 1316:1341 Further, our immunoprecipitation assays depicted the possibility of FOXA1 to undergo O-GalNAc modifications with a decrease of GalNAc residues in the GALNT4 knockdown cells and also impairment in the FOXA1-ERα association. 26541755 2 71 theme proteins 402:409 arg1 modification 386:397 the most complex post-translational modification 350:397 the most complex post-translational modification of proteins 350:409 This glycosylation type is the most complex post-translational modification of proteins, playing important roles during cellular differentiation and in pathological disorders. 26541755 2 71 theme proteins 402:409 arg1 type 342:345 This glycosylation type 323:345 This glycosylation type 323:345 This glycosylation type is the most complex post-translational modification of proteins, playing important roles during cellular differentiation and in pathological disorders. 26541755 6 72 theme expression 1066:1075 arg1 knockdown 1046:1054 knockdown 1046:1054 knockdown of GALNT4 expression in human breast cancer cells 1046:1104 This study found that knockdown of GALNT4 expression in human breast cancer cells attenuated the protein expression of ERα, FOXA1, and Cyclin D1. 26541755 0 73 theme FOXA1 71:75 arg1 glycosylation 77:89 FOXA1 glycosylation 71:89 FOXA1 glycosylation in human breast cancer cells 71:118 GalNAc-T4 putatively modulates the estrogen regulatory network through FOXA1 glycosylation in human breast cancer cells. 26541755 6 74 from cells 1100:1104 arg1 knockdown 1046:1054 knockdown 1046:1054 knockdown of GALNT4 expression in human breast cancer cells 1046:1104 This study found that knockdown of GALNT4 expression in human breast cancer cells attenuated the protein expression of ERα, FOXA1, and Cyclin D1. 26541755 4 75 theme lines 717:721 arg1 panel 684:688 a panel 682:688 a panel of mammary epithelial cell lines 682:721 We investigated the expression of GalNAc-T4 in a panel of mammary epithelial cell lines and found its expression is associated with the estrogen status of the cells. 26408091 1 0 gly O-GlcNAcylation 75:89 arg1 processes 192:200 many fundamental cellular processes 166:200 many fundamental cellular processes 166:200 O-GlcNAcylation is an important post-translational modification and has been implicated in many fundamental cellular processes. 26408091 5 1 theme S112 755:758 arg1 GlcNAcylation 760:772 OGT mediated H2B S112 GlcNAcylation 738:772 OGT mediated H2B S112 GlcNAcylation 738:772 OGT mediated H2B S112 GlcNAcylation increased locally upon the induction of double-strand breaks (DSBs), and depletion of OGT or overexpression of H2B S112A mutant impaired homologous recombination (HR) and nonhomologous end-joining (NHEJ). 26408091 1 2 theme many 166:169 arg1 processes 192:200 many fundamental cellular processes 166:200 many fundamental cellular processes 166:200 O-GlcNAcylation is an important post-translational modification and has been implicated in many fundamental cellular processes. 26408091 4 3 theme H2B 552:554 arg1 GlcNAcylation 561:573 OGT mediated H2B S112 GlcNAcylation 539:573 OGT mediated H2B S112 GlcNAcylation 539:573 In this study, we found that OGT and OGT mediated H2B S112 GlcNAcylation are involved in DNA damage response for maintaining genomic stability and are required for resistance to many DNA-damaging and replication stress-inducing agents. 26408091 7 4 theme damage 1189:1194 arg1 DDR 1206:1208 DDR 1206:1208 DDR 1206:1208 Taken together, our results demonstrate a new function of histone O-GlcNAcylation in DNA damage response (DDR). 26408091 7 4 theme damage 1189:1194 arg1 response 1196:1203 DNA damage response 1185:1203 DNA damage response (DDR) 1185:1209 Taken together, our results demonstrate a new function of histone O-GlcNAcylation in DNA damage response (DDR). 26408091 1 5 theme fundamental 171:181 arg1 processes 192:200 many fundamental cellular processes 166:200 many fundamental cellular processes 166:200 O-GlcNAcylation is an important post-translational modification and has been implicated in many fundamental cellular processes. 26408091 4 6 theme mediated 543:550 arg1 GlcNAcylation 561:573 OGT mediated H2B S112 GlcNAcylation 539:573 OGT mediated H2B S112 GlcNAcylation 539:573 In this study, we found that OGT and OGT mediated H2B S112 GlcNAcylation are involved in DNA damage response for maintaining genomic stability and are required for resistance to many DNA-damaging and replication stress-inducing agents. 26408091 7 7 theme O-GlcNAcylation 1166:1180 arg1 function 1146:1153 a new function 1140:1153 a new function of histone O-GlcNAcylation in DNA damage response (DDR) 1140:1209 Taken together, our results demonstrate a new function of histone O-GlcNAcylation in DNA damage response (DDR). 26408091 3 8 from role 419:422 arg1 response 467:474 DNA damage response 456:474 DNA damage response 456:474 However, the role of this histone modification in DNA damage response has not been studied yet. 26408091 2 9 theme histone 314:320 arg1 GlcNAcylation 344:356 H2B S112 GlcNAcylation 335:356 H2B S112 GlcNAcylation 335:356 Recent studies showed that O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) mediated O-GlcNAcylation of histone H2B Ser 112 (H2B S112 GlcNAcylation) plays an important role in gene transcription. 26408091 2 9 theme histone 314:320 arg1 Ser 326:328 histone H2B Ser 112 314:332 histone H2B Ser 112 (H2B S112 GlcNAcylation) 314:357 Recent studies showed that O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) mediated O-GlcNAcylation of histone H2B Ser 112 (H2B S112 GlcNAcylation) plays an important role in gene transcription. 26408091 2 10 theme H2B 322:324 arg1 GlcNAcylation 344:356 H2B S112 GlcNAcylation 335:356 H2B S112 GlcNAcylation 335:356 Recent studies showed that O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) mediated O-GlcNAcylation of histone H2B Ser 112 (H2B S112 GlcNAcylation) plays an important role in gene transcription. 26408091 2 10 theme H2B 322:324 arg1 Ser 326:328 histone H2B Ser 112 314:332 histone H2B Ser 112 (H2B S112 GlcNAcylation) 314:357 Recent studies showed that O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) mediated O-GlcNAcylation of histone H2B Ser 112 (H2B S112 GlcNAcylation) plays an important role in gene transcription. 26408091 7 11 theme histone 1158:1164 arg1 O-GlcNAcylation 1166:1180 histone O-GlcNAcylation 1158:1180 histone O-GlcNAcylation 1158:1180 Taken together, our results demonstrate a new function of histone O-GlcNAcylation in DNA damage response (DDR). 26408091 5 12 theme nonhomologous 945:957 arg1 NHEJ 972:975 NHEJ 972:975 NHEJ 972:975 OGT mediated H2B S112 GlcNAcylation increased locally upon the induction of double-strand breaks (DSBs), and depletion of OGT or overexpression of H2B S112A mutant impaired homologous recombination (HR) and nonhomologous end-joining (NHEJ). 26408091 5 12 theme nonhomologous 945:957 arg1 end-joining 959:969 nonhomologous end-joining 945:969 nonhomologous end-joining (NHEJ) 945:976 OGT mediated H2B S112 GlcNAcylation increased locally upon the induction of double-strand breaks (DSBs), and depletion of OGT or overexpression of H2B S112A mutant impaired homologous recombination (HR) and nonhomologous end-joining (NHEJ). 26408091 5 13 theme homologous 911:920 arg1 HR 937:938 HR 937:938 HR 937:938 OGT mediated H2B S112 GlcNAcylation increased locally upon the induction of double-strand breaks (DSBs), and depletion of OGT or overexpression of H2B S112A mutant impaired homologous recombination (HR) and nonhomologous end-joining (NHEJ). 26408091 5 13 theme homologous 911:920 arg1 recombination 922:934 homologous recombination 911:934 homologous recombination (HR) 911:939 OGT mediated H2B S112 GlcNAcylation increased locally upon the induction of double-strand breaks (DSBs), and depletion of OGT or overexpression of H2B S112A mutant impaired homologous recombination (HR) and nonhomologous end-joining (NHEJ). 26408091 3 14 mod modification 440:451 arg1 damage 460:465 DNA damage 456:465 DNA damage response 456:474 However, the role of this histone modification in DNA damage response has not been studied yet. 26408091 4 15 theme S112 556:559 arg1 GlcNAcylation 561:573 OGT mediated H2B S112 GlcNAcylation 539:573 OGT mediated H2B S112 GlcNAcylation 539:573 In this study, we found that OGT and OGT mediated H2B S112 GlcNAcylation are involved in DNA damage response for maintaining genomic stability and are required for resistance to many DNA-damaging and replication stress-inducing agents. 26408091 6 16 theme Nijmegen 1030:1037 arg1 syndrome 1048:1055 Nijmegen breakage syndrome 1 1030:1057 Nijmegen breakage syndrome 1 (NBS1) 1030:1064 Mechanistically, H2B S112 GlcNAcylation could bind Nijmegen breakage syndrome 1 (NBS1) and regulate NBS1 foci formation. 26408091 6 16 theme Nijmegen 1030:1037 arg1 NBS1 1060:1063 NBS1 1060:1063 NBS1 1060:1063 Mechanistically, H2B S112 GlcNAcylation could bind Nijmegen breakage syndrome 1 (NBS1) and regulate NBS1 foci formation. 26408091 1 17 theme cellular 183:190 arg1 processes 192:200 many fundamental cellular processes 166:200 many fundamental cellular processes 166:200 O-GlcNAcylation is an important post-translational modification and has been implicated in many fundamental cellular processes. 26408091 5 18 theme OGT 738:740 arg1 GlcNAcylation 760:772 OGT mediated H2B S112 GlcNAcylation 738:772 OGT mediated H2B S112 GlcNAcylation 738:772 OGT mediated H2B S112 GlcNAcylation increased locally upon the induction of double-strand breaks (DSBs), and depletion of OGT or overexpression of H2B S112A mutant impaired homologous recombination (HR) and nonhomologous end-joining (NHEJ). 26408091 5 19 theme H2B 885:887 arg1 mutant 895:900 H2B S112A mutant 885:900 H2B S112A mutant 885:900 OGT mediated H2B S112 GlcNAcylation increased locally upon the induction of double-strand breaks (DSBs), and depletion of OGT or overexpression of H2B S112A mutant impaired homologous recombination (HR) and nonhomologous end-joining (NHEJ). 26408091 2 20 theme mediated 286:293 arg1 O-GlcNAcylation 295:309 O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) mediated O-GlcNAcylation 230:309 O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) mediated O-GlcNAcylation of histone H2B Ser 112 (H2B S112 GlcNAcylation) 230:357 Recent studies showed that O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) mediated O-GlcNAcylation of histone H2B Ser 112 (H2B S112 GlcNAcylation) plays an important role in gene transcription. 26408091 3 21 theme modification 440:451 arg1 role 419:422 the role 415:422 the role of this histone modification in DNA damage response 415:474 However, the role of this histone modification in DNA damage response has not been studied yet. 26408091 0 22 theme mediated 4:11 arg1 GlcNAcylation 30:42 OGT mediated histone H2B S112 GlcNAcylation 0:42 OGT mediated histone H2B S112 GlcNAcylation 0:42 OGT mediated histone H2B S112 GlcNAcylation regulates DNA damage response. 26408091 7 23 from function 1146:1153 arg1 DDR 1206:1208 DDR 1206:1208 DDR 1206:1208 Taken together, our results demonstrate a new function of histone O-GlcNAcylation in DNA damage response (DDR). 26408091 7 23 from function 1146:1153 arg1 response 1196:1203 DNA damage response 1185:1203 DNA damage response (DDR) 1185:1209 Taken together, our results demonstrate a new function of histone O-GlcNAcylation in DNA damage response (DDR). 26408091 7 24 theme new 1142:1144 arg1 function 1146:1153 a new function 1140:1153 a new function of histone O-GlcNAcylation in DNA damage response (DDR) 1140:1209 Taken together, our results demonstrate a new function of histone O-GlcNAcylation in DNA damage response (DDR). 26408091 2 25 theme gene 386:389 arg1 transcription 391:403 gene transcription 386:403 gene transcription 386:403 Recent studies showed that O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) mediated O-GlcNAcylation of histone H2B Ser 112 (H2B S112 GlcNAcylation) plays an important role in gene transcription. 26408091 0 26 theme OGT 0:2 arg1 GlcNAcylation 30:42 OGT mediated histone H2B S112 GlcNAcylation 0:42 OGT mediated histone H2B S112 GlcNAcylation 0:42 OGT mediated histone H2B S112 GlcNAcylation regulates DNA damage response. 26408091 4 27 theme stress-inducing 714:728 arg1 agents 730:735 many DNA-damaging and replication stress-inducing agents 680:735 agents 730:735 In this study, we found that OGT and OGT mediated H2B S112 GlcNAcylation are involved in DNA damage response for maintaining genomic stability and are required for resistance to many DNA-damaging and replication stress-inducing agents. 26408091 5 28 theme OGT 860:862 arg1 depletion 847:855 depletion 847:855 depletion of OGT 847:862 OGT mediated H2B S112 GlcNAcylation increased locally upon the induction of double-strand breaks (DSBs), and depletion of OGT or overexpression of H2B S112A mutant impaired homologous recombination (HR) and nonhomologous end-joining (NHEJ). 26408091 5 28 theme OGT 860:862 arg1 overexpression 867:880 overexpression 867:880 overexpression of H2B S112A mutant 867:900 OGT mediated H2B S112 GlcNAcylation increased locally upon the induction of double-strand breaks (DSBs), and depletion of OGT or overexpression of H2B S112A mutant impaired homologous recombination (HR) and nonhomologous end-joining (NHEJ). 26408091 0 29 theme H2B 21:23 arg1 GlcNAcylation 30:42 OGT mediated histone H2B S112 GlcNAcylation 0:42 OGT mediated histone H2B S112 GlcNAcylation 0:42 OGT mediated histone H2B S112 GlcNAcylation regulates DNA damage response. 26408091 4 30 gly GlcNAcylation 561:573 arg1 response 602:609 DNA damage response 591:609 DNA damage response for maintaining genomic stability 591:643 In this study, we found that OGT and OGT mediated H2B S112 GlcNAcylation are involved in DNA damage response for maintaining genomic stability and are required for resistance to many DNA-damaging and replication stress-inducing agents. 26408091 2 31 theme Ser 326:328 arg1 O-GlcNAcylation 295:309 O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) mediated O-GlcNAcylation 230:309 O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) mediated O-GlcNAcylation of histone H2B Ser 112 (H2B S112 GlcNAcylation) 230:357 Recent studies showed that O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) mediated O-GlcNAcylation of histone H2B Ser 112 (H2B S112 GlcNAcylation) plays an important role in gene transcription. 26408091 3 32 theme damage 460:465 arg1 response 467:474 DNA damage response 456:474 DNA damage response 456:474 However, the role of this histone modification in DNA damage response has not been studied yet. 26408091 0 33 theme histone 13:19 arg1 GlcNAcylation 30:42 OGT mediated histone H2B S112 GlcNAcylation 0:42 OGT mediated histone H2B S112 GlcNAcylation 0:42 OGT mediated histone H2B S112 GlcNAcylation regulates DNA damage response. 26408091 4 34 theme OGT 539:541 arg1 GlcNAcylation 561:573 OGT mediated H2B S112 GlcNAcylation 539:573 OGT mediated H2B S112 GlcNAcylation 539:573 In this study, we found that OGT and OGT mediated H2B S112 GlcNAcylation are involved in DNA damage response for maintaining genomic stability and are required for resistance to many DNA-damaging and replication stress-inducing agents. 26408091 6 35 theme H2B 996:998 arg1 GlcNAcylation 1005:1017 H2B S112 GlcNAcylation 996:1017 H2B S112 GlcNAcylation 996:1017 Mechanistically, H2B S112 GlcNAcylation could bind Nijmegen breakage syndrome 1 (NBS1) and regulate NBS1 foci formation. 26408091 2 36 theme Recent 203:208 arg1 studies 210:216 Recent studies 203:216 Recent studies 203:216 Recent studies showed that O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) mediated O-GlcNAcylation of histone H2B Ser 112 (H2B S112 GlcNAcylation) plays an important role in gene transcription. 26408091 1 37 theme post-translational 107:124 arg1 modification 126:137 an important post-translational modification 94:137 an important post-translational modification 94:137 O-GlcNAcylation is an important post-translational modification and has been implicated in many fundamental cellular processes. 26408091 1 37 theme post-translational 107:124 arg1 O-GlcNAcylation 75:89 O-GlcNAcylation 75:89 O-GlcNAcylation 75:89 O-GlcNAcylation is an important post-translational modification and has been implicated in many fundamental cellular processes. 26408091 4 38 theme damage 595:600 arg1 response 602:609 DNA damage response 591:609 DNA damage response for maintaining genomic stability 591:643 In this study, we found that OGT and OGT mediated H2B S112 GlcNAcylation are involved in DNA damage response for maintaining genomic stability and are required for resistance to many DNA-damaging and replication stress-inducing agents. 26408091 5 39 theme mutant 895:900 arg1 depletion 847:855 depletion 847:855 depletion of OGT 847:862 OGT mediated H2B S112 GlcNAcylation increased locally upon the induction of double-strand breaks (DSBs), and depletion of OGT or overexpression of H2B S112A mutant impaired homologous recombination (HR) and nonhomologous end-joining (NHEJ). 26408091 5 39 theme mutant 895:900 arg1 overexpression 867:880 overexpression 867:880 overexpression of H2B S112A mutant 867:900 OGT mediated H2B S112 GlcNAcylation increased locally upon the induction of double-strand breaks (DSBs), and depletion of OGT or overexpression of H2B S112A mutant impaired homologous recombination (HR) and nonhomologous end-joining (NHEJ). 26408091 2 40 link O-linked 230:237 arg1 GlcNAc 260:265 GlcNAc 260:265 GlcNAc 260:265 Recent studies showed that O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) mediated O-GlcNAcylation of histone H2B Ser 112 (H2B S112 GlcNAcylation) plays an important role in gene transcription. 26408091 2 40 link O-linked 230:237 arg1 N-acetylglucosamine 239:257 O-linked N-acetylglucosamine 230:257 O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) mediated O-GlcNAcylation of histone H2B Ser 112 (H2B S112 GlcNAcylation) 230:357 Recent studies showed that O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) mediated O-GlcNAcylation of histone H2B Ser 112 (H2B S112 GlcNAcylation) plays an important role in gene transcription. 26408091 0 41 theme S112 25:28 arg1 GlcNAcylation 30:42 OGT mediated histone H2B S112 GlcNAcylation 0:42 OGT mediated histone H2B S112 GlcNAcylation 0:42 OGT mediated histone H2B S112 GlcNAcylation regulates DNA damage response. 26408091 5 42 theme double-strand 814:826 arg1 DSBs 836:839 DSBs 836:839 DSBs 836:839 OGT mediated H2B S112 GlcNAcylation increased locally upon the induction of double-strand breaks (DSBs), and depletion of OGT or overexpression of H2B S112A mutant impaired homologous recombination (HR) and nonhomologous end-joining (NHEJ). 26408091 5 42 theme double-strand 814:826 arg1 breaks 828:833 double-strand breaks 814:833 double-strand breaks (DSBs) 814:840 OGT mediated H2B S112 GlcNAcylation increased locally upon the induction of double-strand breaks (DSBs), and depletion of OGT or overexpression of H2B S112A mutant impaired homologous recombination (HR) and nonhomologous end-joining (NHEJ). 26408091 3 43 theme DNA 456:458 arg1 damage 460:465 DNA damage 456:465 DNA damage response 456:474 However, the role of this histone modification in DNA damage response has not been studied yet. 26408091 0 44 theme DNA 54:56 arg1 damage 58:63 DNA damage 54:63 DNA damage response 54:72 OGT mediated histone H2B S112 GlcNAcylation regulates DNA damage response. 26408091 3 45 theme histone 432:438 arg1 modification 440:451 this histone modification 427:451 this histone modification 427:451 However, the role of this histone modification in DNA damage response has not been studied yet. 26408091 5 46 theme S112A 889:893 arg1 mutant 895:900 H2B S112A mutant 885:900 H2B S112A mutant 885:900 OGT mediated H2B S112 GlcNAcylation increased locally upon the induction of double-strand breaks (DSBs), and depletion of OGT or overexpression of H2B S112A mutant impaired homologous recombination (HR) and nonhomologous end-joining (NHEJ). 26408091 2 47 theme O-linked 230:237 arg1 GlcNAc 260:265 GlcNAc 260:265 GlcNAc 260:265 Recent studies showed that O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) mediated O-GlcNAcylation of histone H2B Ser 112 (H2B S112 GlcNAcylation) plays an important role in gene transcription. 26408091 2 47 theme O-linked 230:237 arg1 N-acetylglucosamine 239:257 O-linked N-acetylglucosamine 230:257 O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) mediated O-GlcNAcylation of histone H2B Ser 112 (H2B S112 GlcNAcylation) 230:357 Recent studies showed that O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) mediated O-GlcNAcylation of histone H2B Ser 112 (H2B S112 GlcNAcylation) plays an important role in gene transcription. 26408091 2 48 theme N-acetylglucosamine 239:257 arg1 OGT 281:283 OGT 281:283 OGT 281:283 Recent studies showed that O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) mediated O-GlcNAcylation of histone H2B Ser 112 (H2B S112 GlcNAcylation) plays an important role in gene transcription. 26408091 2 48 theme N-acetylglucosamine 239:257 arg1 transferase 268:278 O-linked N-acetylglucosamine (GlcNAc) transferase 230:278 O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) mediated O-GlcNAcylation of histone H2B Ser 112 (H2B S112 GlcNAcylation) 230:357 Recent studies showed that O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) mediated O-GlcNAcylation of histone H2B Ser 112 (H2B S112 GlcNAcylation) plays an important role in gene transcription. 26408091 4 49 theme many 680:683 arg1 DNA-damaging 685:696 many DNA-damaging and replication stress-inducing agents 680:735 DNA-damaging 685:696 In this study, we found that OGT and OGT mediated H2B S112 GlcNAcylation are involved in DNA damage response for maintaining genomic stability and are required for resistance to many DNA-damaging and replication stress-inducing agents. 26408091 6 50 theme S112 1000:1003 arg1 GlcNAcylation 1005:1017 H2B S112 GlcNAcylation 996:1017 H2B S112 GlcNAcylation 996:1017 Mechanistically, H2B S112 GlcNAcylation could bind Nijmegen breakage syndrome 1 (NBS1) and regulate NBS1 foci formation. 26408091 5 51 theme H2B 751:753 arg1 GlcNAcylation 760:772 OGT mediated H2B S112 GlcNAcylation 738:772 OGT mediated H2B S112 GlcNAcylation 738:772 OGT mediated H2B S112 GlcNAcylation increased locally upon the induction of double-strand breaks (DSBs), and depletion of OGT or overexpression of H2B S112A mutant impaired homologous recombination (HR) and nonhomologous end-joining (NHEJ). 26408091 2 52 theme S112 339:342 arg1 GlcNAcylation 344:356 H2B S112 GlcNAcylation 335:356 H2B S112 GlcNAcylation 335:356 Recent studies showed that O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) mediated O-GlcNAcylation of histone H2B Ser 112 (H2B S112 GlcNAcylation) plays an important role in gene transcription. 26408091 2 52 theme S112 339:342 arg1 Ser 326:328 histone H2B Ser 112 314:332 histone H2B Ser 112 (H2B S112 GlcNAcylation) 314:357 Recent studies showed that O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) mediated O-GlcNAcylation of histone H2B Ser 112 (H2B S112 GlcNAcylation) plays an important role in gene transcription. 26408091 1 53 theme important 97:105 arg1 modification 126:137 an important post-translational modification 94:137 an important post-translational modification 94:137 O-GlcNAcylation is an important post-translational modification and has been implicated in many fundamental cellular processes. 26408091 1 53 theme important 97:105 arg1 O-GlcNAcylation 75:89 O-GlcNAcylation 75:89 O-GlcNAcylation 75:89 O-GlcNAcylation is an important post-translational modification and has been implicated in many fundamental cellular processes. 26408091 6 54 theme foci 1084:1087 arg1 formation 1089:1097 NBS1 foci formation 1079:1097 NBS1 foci formation 1079:1097 Mechanistically, H2B S112 GlcNAcylation could bind Nijmegen breakage syndrome 1 (NBS1) and regulate NBS1 foci formation. 26408091 5 55 theme breaks 828:833 arg1 induction 801:809 the induction 797:809 the induction of double-strand breaks (DSBs) 797:840 OGT mediated H2B S112 GlcNAcylation increased locally upon the induction of double-strand breaks (DSBs), and depletion of OGT or overexpression of H2B S112A mutant impaired homologous recombination (HR) and nonhomologous end-joining (NHEJ). 26408091 7 56 theme DNA 1185:1187 arg1 damage 1189:1194 DNA damage 1185:1194 DNA damage response (DDR) 1185:1209 Taken together, our results demonstrate a new function of histone O-GlcNAcylation in DNA damage response (DDR). 26408091 2 57 theme H2B 335:337 arg1 GlcNAcylation 344:356 H2B S112 GlcNAcylation 335:356 H2B S112 GlcNAcylation 335:356 Recent studies showed that O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) mediated O-GlcNAcylation of histone H2B Ser 112 (H2B S112 GlcNAcylation) plays an important role in gene transcription. 26408091 2 57 theme H2B 335:337 arg1 Ser 326:328 histone H2B Ser 112 314:332 histone H2B Ser 112 (H2B S112 GlcNAcylation) 314:357 Recent studies showed that O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) mediated O-GlcNAcylation of histone H2B Ser 112 (H2B S112 GlcNAcylation) plays an important role in gene transcription. 26408091 4 58 theme replication 702:712 arg1 agents 730:735 many DNA-damaging and replication stress-inducing agents 680:735 agents 730:735 In this study, we found that OGT and OGT mediated H2B S112 GlcNAcylation are involved in DNA damage response for maintaining genomic stability and are required for resistance to many DNA-damaging and replication stress-inducing agents. 26408091 5 59 theme mediated 742:749 arg1 GlcNAcylation 760:772 OGT mediated H2B S112 GlcNAcylation 738:772 OGT mediated H2B S112 GlcNAcylation 738:772 OGT mediated H2B S112 GlcNAcylation increased locally upon the induction of double-strand breaks (DSBs), and depletion of OGT or overexpression of H2B S112A mutant impaired homologous recombination (HR) and nonhomologous end-joining (NHEJ). 26408091 6 60 theme breakage 1039:1046 arg1 syndrome 1048:1055 Nijmegen breakage syndrome 1 1030:1057 Nijmegen breakage syndrome 1 (NBS1) 1030:1064 Mechanistically, H2B S112 GlcNAcylation could bind Nijmegen breakage syndrome 1 (NBS1) and regulate NBS1 foci formation. 26408091 6 60 theme breakage 1039:1046 arg1 NBS1 1060:1063 NBS1 1060:1063 NBS1 1060:1063 Mechanistically, H2B S112 GlcNAcylation could bind Nijmegen breakage syndrome 1 (NBS1) and regulate NBS1 foci formation. 26408091 6 61 theme NBS1 1079:1082 arg1 formation 1089:1097 NBS1 foci formation 1079:1097 NBS1 foci formation 1079:1097 Mechanistically, H2B S112 GlcNAcylation could bind Nijmegen breakage syndrome 1 (NBS1) and regulate NBS1 foci formation. 26408091 4 62 theme genomic 627:633 arg1 stability 635:643 genomic stability 627:643 genomic stability 627:643 In this study, we found that OGT and OGT mediated H2B S112 GlcNAcylation are involved in DNA damage response for maintaining genomic stability and are required for resistance to many DNA-damaging and replication stress-inducing agents. 26408091 4 63 theme DNA 591:593 arg1 damage 595:600 DNA damage 591:600 DNA damage response for maintaining genomic stability 591:643 In this study, we found that OGT and OGT mediated H2B S112 GlcNAcylation are involved in DNA damage response for maintaining genomic stability and are required for resistance to many DNA-damaging and replication stress-inducing agents. 26408091 0 64 theme damage 58:63 arg1 response 65:72 DNA damage response 54:72 DNA damage response 54:72 OGT mediated histone H2B S112 GlcNAcylation regulates DNA damage response. 26408091 2 65 theme transferase 268:278 arg1 O-GlcNAcylation 295:309 O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) mediated O-GlcNAcylation 230:309 O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) mediated O-GlcNAcylation of histone H2B Ser 112 (H2B S112 GlcNAcylation) 230:357 Recent studies showed that O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) mediated O-GlcNAcylation of histone H2B Ser 112 (H2B S112 GlcNAcylation) plays an important role in gene transcription. 26408091 2 66 theme important 368:376 arg1 role 378:381 an important role 365:381 an important role 365:381 Recent studies showed that O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) mediated O-GlcNAcylation of histone H2B Ser 112 (H2B S112 GlcNAcylation) plays an important role in gene transcription. 25344697 0 0 theme amyloid 79:85 arg1 formation 94:102 amyloid plaque formation 79:102 amyloid plaque formation 79:102 Pharmacological inhibition of O-GlcNAcase (OGA) prevents cognitive decline and amyloid plaque formation in bigenic tau/APP mutant mice. 25344697 4 1 theme human 687:691 arg1 tau 693:695 mutant human tau 680:695 mutant human tau 680:695 RESULTS We treated double transgenic TAPP mice, which express both mutant human tau and amyloid precursor protein (APP), with a highly selective orally bioavailable inhibitor of the enzyme responsible for removing O-GlcNAc (OGA) to increase O-GlcNAc in the brain. 25344697 2 2 theme post-translational 338:355 arg1 modification 357:368 post-translational modification 338:368 post-translational modification of nuclear and cytoplasmic proteins 338:404 Increasing the quantity of the O-linked N-acetylglucosamine (O-GlcNAc) post-translational modification of nuclear and cytoplasmic proteins slows neurodegeneration and blocks the formation of NFTs in a tauopathy mouse model. 25344697 1 3 theme disease 253:259 arg1 plaques 155:161 BACKGROUND Amyloid plaques 136:161 BACKGROUND Amyloid plaques 136:161 BACKGROUND Amyloid plaques and neurofibrillary tangles (NFTs) are the defining pathological hallmarks of Alzheimer's disease (AD). 25344697 1 3 theme disease 253:259 arg1 hallmarks 228:236 the defining pathological hallmarks 202:236 the defining pathological hallmarks of Alzheimer's disease (AD) 202:264 BACKGROUND Amyloid plaques and neurofibrillary tangles (NFTs) are the defining pathological hallmarks of Alzheimer's disease (AD). 25344697 1 3 theme disease 253:259 arg1 tangles 183:189 neurofibrillary tangles 167:189 neurofibrillary tangles (NFTs) 167:196 BACKGROUND Amyloid plaques and neurofibrillary tangles (NFTs) are the defining pathological hallmarks of Alzheimer's disease (AD). 25344697 5 4 theme decreased 983:991 arg1 levels 1011:1016 decreased β-amyloid peptide levels 983:1016 decreased β-amyloid peptide levels 983:1016 We find that increased O-GlcNAc levels block cognitive decline in the TAPP mice and this effect parallels decreased β-amyloid peptide levels and decreased levels of amyloid plaques. 25344697 5 5 theme cognitive 922:930 arg1 decline 932:938 cognitive decline 922:938 cognitive decline in the TAPP mice 922:955 We find that increased O-GlcNAc levels block cognitive decline in the TAPP mice and this effect parallels decreased β-amyloid peptide levels and decreased levels of amyloid plaques. 25344697 5 6 from decline 932:938 arg1 mice 952:955 the TAPP mice 943:955 the TAPP mice 943:955 We find that increased O-GlcNAc levels block cognitive decline in the TAPP mice and this effect parallels decreased β-amyloid peptide levels and decreased levels of amyloid plaques. 25344697 0 7 theme plaque 87:92 arg1 formation 94:102 amyloid plaque formation 79:102 amyloid plaque formation 79:102 Pharmacological inhibition of O-GlcNAcase (OGA) prevents cognitive decline and amyloid plaque formation in bigenic tau/APP mutant mice. 25344697 6 8 theme β-amyloid 1130:1138 arg1 pathology 1140:1148 β-amyloid pathology 1130:1148 β-amyloid pathology 1130:1148 CONCLUSIONS This study indicates that increased O-GlcNAc can influence β-amyloid pathology in the presence of tau pathology. 25344697 4 9 theme amyloid 701:707 arg1 APP 728:730 APP 728:730 APP 728:730 RESULTS We treated double transgenic TAPP mice, which express both mutant human tau and amyloid precursor protein (APP), with a highly selective orally bioavailable inhibitor of the enzyme responsible for removing O-GlcNAc (OGA) to increase O-GlcNAc in the brain. 25344697 4 9 theme amyloid 701:707 arg1 protein 719:725 amyloid precursor protein 701:725 amyloid precursor protein (APP) 701:731 RESULTS We treated double transgenic TAPP mice, which express both mutant human tau and amyloid precursor protein (APP), with a highly selective orally bioavailable inhibitor of the enzyme responsible for removing O-GlcNAc (OGA) to increase O-GlcNAc in the brain. 25344697 0 10 theme bigenic 107:113 arg1 mice 130:133 bigenic tau/APP mutant mice 107:133 bigenic tau/APP mutant mice 107:133 Pharmacological inhibition of O-GlcNAcase (OGA) prevents cognitive decline and amyloid plaque formation in bigenic tau/APP mutant mice. 25344697 7 11 theme Alzheimer 1292:1300 arg1 disease 1302:1308 Alzheimer disease 1292:1308 Alzheimer disease 1292:1308 The findings provide good support for OGA as a promising therapeutic target to alter disease progression in Alzheimer disease. 25344697 1 12 theme neurofibrillary 167:181 arg1 NFTs 192:195 NFTs 192:195 NFTs 192:195 BACKGROUND Amyloid plaques and neurofibrillary tangles (NFTs) are the defining pathological hallmarks of Alzheimer's disease (AD). 25344697 1 12 theme neurofibrillary 167:181 arg1 plaques 155:161 BACKGROUND Amyloid plaques 136:161 BACKGROUND Amyloid plaques 136:161 BACKGROUND Amyloid plaques and neurofibrillary tangles (NFTs) are the defining pathological hallmarks of Alzheimer's disease (AD). 25344697 1 12 theme neurofibrillary 167:181 arg1 tangles 183:189 neurofibrillary tangles 167:189 neurofibrillary tangles (NFTs) 167:196 BACKGROUND Amyloid plaques and neurofibrillary tangles (NFTs) are the defining pathological hallmarks of Alzheimer's disease (AD). 25344697 1 12 theme neurofibrillary 167:181 arg1 hallmarks 228:236 the defining pathological hallmarks 202:236 the defining pathological hallmarks of Alzheimer's disease (AD) 202:264 BACKGROUND Amyloid plaques and neurofibrillary tangles (NFTs) are the defining pathological hallmarks of Alzheimer's disease (AD). 25344697 0 13 theme Pharmacological 0:14 arg1 inhibition 16:25 Pharmacological inhibition 0:25 Pharmacological inhibition of O-GlcNAcase (OGA) 0:46 Pharmacological inhibition of O-GlcNAcase (OGA) prevents cognitive decline and amyloid plaque formation in bigenic tau/APP mutant mice. 25344697 2 14 theme proteins 397:404 arg1 modification 357:368 post-translational modification 338:368 post-translational modification of nuclear and cytoplasmic proteins 338:404 Increasing the quantity of the O-linked N-acetylglucosamine (O-GlcNAc) post-translational modification of nuclear and cytoplasmic proteins slows neurodegeneration and blocks the formation of NFTs in a tauopathy mouse model. 25344697 2 15 theme O-linked 298:305 arg1 O-GlcNAc 328:335 O-GlcNAc 328:335 O-GlcNAc 328:335 Increasing the quantity of the O-linked N-acetylglucosamine (O-GlcNAc) post-translational modification of nuclear and cytoplasmic proteins slows neurodegeneration and blocks the formation of NFTs in a tauopathy mouse model. 25344697 2 15 theme O-linked 298:305 arg1 N-acetylglucosamine 307:325 the O-linked N-acetylglucosamine 294:325 the O-linked N-acetylglucosamine (O-GlcNAc) 294:336 Increasing the quantity of the O-linked N-acetylglucosamine (O-GlcNAc) post-translational modification of nuclear and cytoplasmic proteins slows neurodegeneration and blocks the formation of NFTs in a tauopathy mouse model. 25344697 7 16 theme therapeutic 1241:1251 arg1 target 1253:1258 a promising therapeutic target 1229:1258 a promising therapeutic target to alter disease progression in Alzheimer disease 1229:1308 The findings provide good support for OGA as a promising therapeutic target to alter disease progression in Alzheimer disease. 25344697 7 16 theme therapeutic 1241:1251 arg1 support 1210:1216 good support 1205:1216 good support for OGA 1205:1224 The findings provide good support for OGA as a promising therapeutic target to alter disease progression in Alzheimer disease. 25344697 2 17 theme cytoplasmic 385:395 arg1 proteins 397:404 nuclear and cytoplasmic proteins 373:404 nuclear and cytoplasmic proteins 373:404 Increasing the quantity of the O-linked N-acetylglucosamine (O-GlcNAc) post-translational modification of nuclear and cytoplasmic proteins slows neurodegeneration and blocks the formation of NFTs in a tauopathy mouse model. 25344697 2 18 theme NFTs 458:461 arg1 formation 445:453 the formation 441:453 the formation of NFTs 441:461 Increasing the quantity of the O-linked N-acetylglucosamine (O-GlcNAc) post-translational modification of nuclear and cytoplasmic proteins slows neurodegeneration and blocks the formation of NFTs in a tauopathy mouse model. 25344697 6 19 theme pathology 1173:1181 arg1 presence 1157:1164 the presence 1153:1164 the presence of tau pathology 1153:1181 CONCLUSIONS This study indicates that increased O-GlcNAc can influence β-amyloid pathology in the presence of tau pathology. 25344697 5 20 theme decreased 1022:1030 arg1 levels 1032:1037 decreased levels 1022:1037 decreased levels of amyloid plaques 1022:1056 We find that increased O-GlcNAc levels block cognitive decline in the TAPP mice and this effect parallels decreased β-amyloid peptide levels and decreased levels of amyloid plaques. 25344697 3 21 theme plaques 571:577 arg1 formation 550:558 the formation 546:558 the formation of amyloid plaques 546:577 It remains unknown, however, if O-GlcNAc can influence the formation of amyloid plaques in the presence of tau pathology. 25344697 4 22 dep selective 748:756 arg1 bioavailable 765:776 bioavailable 765:776 bioavailable 765:776 RESULTS We treated double transgenic TAPP mice, which express both mutant human tau and amyloid precursor protein (APP), with a highly selective orally bioavailable inhibitor of the enzyme responsible for removing O-GlcNAc (OGA) to increase O-GlcNAc in the brain. 25344697 0 23 theme O-GlcNAcase 30:40 arg1 inhibition 16:25 Pharmacological inhibition 0:25 Pharmacological inhibition of O-GlcNAcase (OGA) 0:46 Pharmacological inhibition of O-GlcNAcase (OGA) prevents cognitive decline and amyloid plaque formation in bigenic tau/APP mutant mice. 25344697 3 24 theme tau 598:600 arg1 pathology 602:610 tau pathology 598:610 tau pathology 598:610 It remains unknown, however, if O-GlcNAc can influence the formation of amyloid plaques in the presence of tau pathology. 25344697 0 25 theme mutant 123:128 arg1 mice 130:133 bigenic tau/APP mutant mice 107:133 bigenic tau/APP mutant mice 107:133 Pharmacological inhibition of O-GlcNAcase (OGA) prevents cognitive decline and amyloid plaque formation in bigenic tau/APP mutant mice. 25344697 5 26 theme β-amyloid 993:1001 arg1 levels 1011:1016 decreased β-amyloid peptide levels 983:1016 decreased β-amyloid peptide levels 983:1016 We find that increased O-GlcNAc levels block cognitive decline in the TAPP mice and this effect parallels decreased β-amyloid peptide levels and decreased levels of amyloid plaques. 25344697 5 27 theme peptide 1003:1009 arg1 levels 1011:1016 decreased β-amyloid peptide levels 983:1016 decreased β-amyloid peptide levels 983:1016 We find that increased O-GlcNAc levels block cognitive decline in the TAPP mice and this effect parallels decreased β-amyloid peptide levels and decreased levels of amyloid plaques. 25344697 5 28 theme O-GlcNAc 900:907 arg1 levels 909:914 increased O-GlcNAc levels 890:914 increased O-GlcNAc levels 890:914 We find that increased O-GlcNAc levels block cognitive decline in the TAPP mice and this effect parallels decreased β-amyloid peptide levels and decreased levels of amyloid plaques. 25344697 0 29 theme tau/APP 115:121 arg1 mice 130:133 bigenic tau/APP mutant mice 107:133 bigenic tau/APP mutant mice 107:133 Pharmacological inhibition of O-GlcNAcase (OGA) prevents cognitive decline and amyloid plaque formation in bigenic tau/APP mutant mice. 25344697 4 30 theme mutant 680:685 arg1 tau 693:695 mutant human tau 680:695 mutant human tau 680:695 RESULTS We treated double transgenic TAPP mice, which express both mutant human tau and amyloid precursor protein (APP), with a highly selective orally bioavailable inhibitor of the enzyme responsible for removing O-GlcNAc (OGA) to increase O-GlcNAc in the brain. 25344697 2 31 theme nuclear 373:379 arg1 proteins 397:404 nuclear and cytoplasmic proteins 373:404 nuclear and cytoplasmic proteins 373:404 Increasing the quantity of the O-linked N-acetylglucosamine (O-GlcNAc) post-translational modification of nuclear and cytoplasmic proteins slows neurodegeneration and blocks the formation of NFTs in a tauopathy mouse model. 25344697 7 32 theme disease 1269:1275 arg1 progression 1277:1287 disease progression 1269:1287 disease progression in Alzheimer disease 1269:1308 The findings provide good support for OGA as a promising therapeutic target to alter disease progression in Alzheimer disease. 25344697 6 33 theme increased 1097:1105 arg1 O-GlcNAc 1107:1114 increased O-GlcNAc 1097:1114 increased O-GlcNAc 1097:1114 CONCLUSIONS This study indicates that increased O-GlcNAc can influence β-amyloid pathology in the presence of tau pathology. 25344697 6 34 dep CONCLUSIONS 1059:1069 arg1 indicates 1082:1090 indicates 1082:1090 indicates that increased O-GlcNAc can influence β-amyloid pathology in the presence of tau pathology 1082:1181 CONCLUSIONS This study indicates that increased O-GlcNAc can influence β-amyloid pathology in the presence of tau pathology. 25344697 6 35 theme tau 1169:1171 arg1 pathology 1173:1181 tau pathology 1169:1181 tau pathology 1169:1181 CONCLUSIONS This study indicates that increased O-GlcNAc can influence β-amyloid pathology in the presence of tau pathology. 25344697 4 36 theme transgenic 639:648 arg1 mice 655:658 double transgenic TAPP mice 632:658 double transgenic TAPP mice 632:658 RESULTS We treated double transgenic TAPP mice, which express both mutant human tau and amyloid precursor protein (APP), with a highly selective orally bioavailable inhibitor of the enzyme responsible for removing O-GlcNAc (OGA) to increase O-GlcNAc in the brain. 25344697 2 37 theme mouse 478:482 arg1 model 484:488 a tauopathy mouse model 466:488 a tauopathy mouse model 466:488 Increasing the quantity of the O-linked N-acetylglucosamine (O-GlcNAc) post-translational modification of nuclear and cytoplasmic proteins slows neurodegeneration and blocks the formation of NFTs in a tauopathy mouse model. 25344697 0 38 from decline 67:73 arg1 mice 130:133 bigenic tau/APP mutant mice 107:133 bigenic tau/APP mutant mice 107:133 Pharmacological inhibition of O-GlcNAcase (OGA) prevents cognitive decline and amyloid plaque formation in bigenic tau/APP mutant mice. 25344697 1 39 theme defining 206:213 arg1 plaques 155:161 BACKGROUND Amyloid plaques 136:161 BACKGROUND Amyloid plaques 136:161 BACKGROUND Amyloid plaques and neurofibrillary tangles (NFTs) are the defining pathological hallmarks of Alzheimer's disease (AD). 25344697 1 39 theme defining 206:213 arg1 hallmarks 228:236 the defining pathological hallmarks 202:236 the defining pathological hallmarks of Alzheimer's disease (AD) 202:264 BACKGROUND Amyloid plaques and neurofibrillary tangles (NFTs) are the defining pathological hallmarks of Alzheimer's disease (AD). 25344697 1 39 theme defining 206:213 arg1 tangles 183:189 neurofibrillary tangles 167:189 neurofibrillary tangles (NFTs) 167:196 BACKGROUND Amyloid plaques and neurofibrillary tangles (NFTs) are the defining pathological hallmarks of Alzheimer's disease (AD). 25344697 2 40 theme tauopathy 468:476 arg1 model 484:488 a tauopathy mouse model 466:488 a tauopathy mouse model 466:488 Increasing the quantity of the O-linked N-acetylglucosamine (O-GlcNAc) post-translational modification of nuclear and cytoplasmic proteins slows neurodegeneration and blocks the formation of NFTs in a tauopathy mouse model. 25344697 5 41 theme plaques 1050:1056 arg1 levels 1011:1016 decreased β-amyloid peptide levels 983:1016 decreased β-amyloid peptide levels 983:1016 We find that increased O-GlcNAc levels block cognitive decline in the TAPP mice and this effect parallels decreased β-amyloid peptide levels and decreased levels of amyloid plaques. 25344697 5 41 theme plaques 1050:1056 arg1 levels 1032:1037 decreased levels 1022:1037 decreased levels of amyloid plaques 1022:1056 We find that increased O-GlcNAc levels block cognitive decline in the TAPP mice and this effect parallels decreased β-amyloid peptide levels and decreased levels of amyloid plaques. 25344697 4 42 theme responsible 802:812 arg1 enzyme 795:800 the enzyme 791:800 the enzyme responsible for removing O-GlcNAc (OGA) to increase O-GlcNAc in the brain 791:874 RESULTS We treated double transgenic TAPP mice, which express both mutant human tau and amyloid precursor protein (APP), with a highly selective orally bioavailable inhibitor of the enzyme responsible for removing O-GlcNAc (OGA) to increase O-GlcNAc in the brain. 25344697 2 43 link O-linked 298:305 arg1 O-GlcNAc 328:335 O-GlcNAc 328:335 O-GlcNAc 328:335 Increasing the quantity of the O-linked N-acetylglucosamine (O-GlcNAc) post-translational modification of nuclear and cytoplasmic proteins slows neurodegeneration and blocks the formation of NFTs in a tauopathy mouse model. 25344697 2 43 link O-linked 298:305 arg1 N-acetylglucosamine 307:325 the O-linked N-acetylglucosamine 294:325 the O-linked N-acetylglucosamine (O-GlcNAc) 294:336 Increasing the quantity of the O-linked N-acetylglucosamine (O-GlcNAc) post-translational modification of nuclear and cytoplasmic proteins slows neurodegeneration and blocks the formation of NFTs in a tauopathy mouse model. 25344697 4 44 dep RESULTS 613:619 arg1 treated 624:630 treated 624:630 treated 624:630 RESULTS We treated double transgenic TAPP mice, which express both mutant human tau and amyloid precursor protein (APP), with a highly selective orally bioavailable inhibitor of the enzyme responsible for removing O-GlcNAc (OGA) to increase O-GlcNAc in the brain. 25344697 4 45 theme enzyme 795:800 arg1 inhibitor 778:786 a highly selective orally bioavailable inhibitor 739:786 a highly selective orally bioavailable inhibitor of the enzyme responsible for removing O-GlcNAc (OGA) to increase O-GlcNAc in the brain 739:874 RESULTS We treated double transgenic TAPP mice, which express both mutant human tau and amyloid precursor protein (APP), with a highly selective orally bioavailable inhibitor of the enzyme responsible for removing O-GlcNAc (OGA) to increase O-GlcNAc in the brain. 25344697 7 46 from progression 1277:1287 arg1 disease 1302:1308 Alzheimer disease 1292:1308 Alzheimer disease 1292:1308 The findings provide good support for OGA as a promising therapeutic target to alter disease progression in Alzheimer disease. 25344697 5 47 theme amyloid 1042:1048 arg1 plaques 1050:1056 amyloid plaques 1042:1056 amyloid plaques 1042:1056 We find that increased O-GlcNAc levels block cognitive decline in the TAPP mice and this effect parallels decreased β-amyloid peptide levels and decreased levels of amyloid plaques. 25344697 3 48 theme amyloid 563:569 arg1 plaques 571:577 amyloid plaques 563:577 amyloid plaques 563:577 It remains unknown, however, if O-GlcNAc can influence the formation of amyloid plaques in the presence of tau pathology. 25344697 5 49 theme increased 890:898 arg1 levels 909:914 increased O-GlcNAc levels 890:914 increased O-GlcNAc levels 890:914 We find that increased O-GlcNAc levels block cognitive decline in the TAPP mice and this effect parallels decreased β-amyloid peptide levels and decreased levels of amyloid plaques. 25344697 5 50 theme TAPP 947:950 arg1 mice 952:955 the TAPP mice 943:955 the TAPP mice 943:955 We find that increased O-GlcNAc levels block cognitive decline in the TAPP mice and this effect parallels decreased β-amyloid peptide levels and decreased levels of amyloid plaques. 25344697 4 51 theme precursor 709:717 arg1 APP 728:730 APP 728:730 APP 728:730 RESULTS We treated double transgenic TAPP mice, which express both mutant human tau and amyloid precursor protein (APP), with a highly selective orally bioavailable inhibitor of the enzyme responsible for removing O-GlcNAc (OGA) to increase O-GlcNAc in the brain. 25344697 4 51 theme precursor 709:717 arg1 protein 719:725 amyloid precursor protein 701:725 amyloid precursor protein (APP) 701:731 RESULTS We treated double transgenic TAPP mice, which express both mutant human tau and amyloid precursor protein (APP), with a highly selective orally bioavailable inhibitor of the enzyme responsible for removing O-GlcNAc (OGA) to increase O-GlcNAc in the brain. 25344697 1 52 theme pathological 215:226 arg1 plaques 155:161 BACKGROUND Amyloid plaques 136:161 BACKGROUND Amyloid plaques 136:161 BACKGROUND Amyloid plaques and neurofibrillary tangles (NFTs) are the defining pathological hallmarks of Alzheimer's disease (AD). 25344697 1 52 theme pathological 215:226 arg1 hallmarks 228:236 the defining pathological hallmarks 202:236 the defining pathological hallmarks of Alzheimer's disease (AD) 202:264 BACKGROUND Amyloid plaques and neurofibrillary tangles (NFTs) are the defining pathological hallmarks of Alzheimer's disease (AD). 25344697 1 52 theme pathological 215:226 arg1 tangles 183:189 neurofibrillary tangles 167:189 neurofibrillary tangles (NFTs) 167:196 BACKGROUND Amyloid plaques and neurofibrillary tangles (NFTs) are the defining pathological hallmarks of Alzheimer's disease (AD). 25344697 0 53 from formation 94:102 arg1 mice 130:133 bigenic tau/APP mutant mice 107:133 bigenic tau/APP mutant mice 107:133 Pharmacological inhibition of O-GlcNAcase (OGA) prevents cognitive decline and amyloid plaque formation in bigenic tau/APP mutant mice. 25344697 4 54 theme selective 748:756 arg1 inhibitor 778:786 a highly selective orally bioavailable inhibitor 739:786 a highly selective orally bioavailable inhibitor of the enzyme responsible for removing O-GlcNAc (OGA) to increase O-GlcNAc in the brain 739:874 RESULTS We treated double transgenic TAPP mice, which express both mutant human tau and amyloid precursor protein (APP), with a highly selective orally bioavailable inhibitor of the enzyme responsible for removing O-GlcNAc (OGA) to increase O-GlcNAc in the brain. 25344697 2 55 theme N-acetylglucosamine 307:325 arg1 quantity 282:289 the quantity 278:289 the quantity of the O-linked N-acetylglucosamine (O-GlcNAc) 278:336 Increasing the quantity of the O-linked N-acetylglucosamine (O-GlcNAc) post-translational modification of nuclear and cytoplasmic proteins slows neurodegeneration and blocks the formation of NFTs in a tauopathy mouse model. 25344697 7 56 theme promising 1231:1239 arg1 target 1253:1258 a promising therapeutic target 1229:1258 a promising therapeutic target to alter disease progression in Alzheimer disease 1229:1308 The findings provide good support for OGA as a promising therapeutic target to alter disease progression in Alzheimer disease. 25344697 7 56 theme promising 1231:1239 arg1 support 1210:1216 good support 1205:1216 good support for OGA 1205:1224 The findings provide good support for OGA as a promising therapeutic target to alter disease progression in Alzheimer disease. 25344697 7 57 theme good 1205:1208 arg1 target 1253:1258 a promising therapeutic target 1229:1258 a promising therapeutic target to alter disease progression in Alzheimer disease 1229:1308 The findings provide good support for OGA as a promising therapeutic target to alter disease progression in Alzheimer disease. 25344697 7 57 theme good 1205:1208 arg1 support 1210:1216 good support 1205:1216 good support for OGA 1205:1224 The findings provide good support for OGA as a promising therapeutic target to alter disease progression in Alzheimer disease. 25344697 4 58 theme double 632:637 arg1 mice 655:658 double transgenic TAPP mice 632:658 double transgenic TAPP mice 632:658 RESULTS We treated double transgenic TAPP mice, which express both mutant human tau and amyloid precursor protein (APP), with a highly selective orally bioavailable inhibitor of the enzyme responsible for removing O-GlcNAc (OGA) to increase O-GlcNAc in the brain. 25344697 2 59 dep slows 406:410 arg1 Increasing 267:276 Increasing 267:276 Increasing the quantity of the O-linked N-acetylglucosamine (O-GlcNAc) 267:336 Increasing the quantity of the O-linked N-acetylglucosamine (O-GlcNAc) post-translational modification of nuclear and cytoplasmic proteins slows neurodegeneration and blocks the formation of NFTs in a tauopathy mouse model. 25344697 1 60 theme BACKGROUND 136:145 arg1 plaques 155:161 BACKGROUND Amyloid plaques 136:161 BACKGROUND Amyloid plaques 136:161 BACKGROUND Amyloid plaques and neurofibrillary tangles (NFTs) are the defining pathological hallmarks of Alzheimer's disease (AD). 25344697 1 60 theme BACKGROUND 136:145 arg1 hallmarks 228:236 the defining pathological hallmarks 202:236 the defining pathological hallmarks of Alzheimer's disease (AD) 202:264 BACKGROUND Amyloid plaques and neurofibrillary tangles (NFTs) are the defining pathological hallmarks of Alzheimer's disease (AD). 25344697 1 60 theme BACKGROUND 136:145 arg1 tangles 183:189 neurofibrillary tangles 167:189 neurofibrillary tangles (NFTs) 167:196 BACKGROUND Amyloid plaques and neurofibrillary tangles (NFTs) are the defining pathological hallmarks of Alzheimer's disease (AD). 25344697 4 61 theme TAPP 650:653 arg1 mice 655:658 double transgenic TAPP mice 632:658 double transgenic TAPP mice 632:658 RESULTS We treated double transgenic TAPP mice, which express both mutant human tau and amyloid precursor protein (APP), with a highly selective orally bioavailable inhibitor of the enzyme responsible for removing O-GlcNAc (OGA) to increase O-GlcNAc in the brain. 25344697 0 62 theme cognitive 57:65 arg1 decline 67:73 cognitive decline 57:73 cognitive decline 57:73 Pharmacological inhibition of O-GlcNAcase (OGA) prevents cognitive decline and amyloid plaque formation in bigenic tau/APP mutant mice. 25344697 3 63 theme pathology 602:610 arg1 presence 586:593 the presence 582:593 the presence of tau pathology 582:610 It remains unknown, however, if O-GlcNAc can influence the formation of amyloid plaques in the presence of tau pathology. 25344697 1 64 theme Amyloid 147:153 arg1 plaques 155:161 BACKGROUND Amyloid plaques 136:161 BACKGROUND Amyloid plaques 136:161 BACKGROUND Amyloid plaques and neurofibrillary tangles (NFTs) are the defining pathological hallmarks of Alzheimer's disease (AD). 25344697 1 64 theme Amyloid 147:153 arg1 hallmarks 228:236 the defining pathological hallmarks 202:236 the defining pathological hallmarks of Alzheimer's disease (AD) 202:264 BACKGROUND Amyloid plaques and neurofibrillary tangles (NFTs) are the defining pathological hallmarks of Alzheimer's disease (AD). 25344697 1 64 theme Amyloid 147:153 arg1 tangles 183:189 neurofibrillary tangles 167:189 neurofibrillary tangles (NFTs) 167:196 BACKGROUND Amyloid plaques and neurofibrillary tangles (NFTs) are the defining pathological hallmarks of Alzheimer's disease (AD). 24619076 2 0 from stratification 479:492 arg1 patients 497:504 patients 497:504 patients with gastric cancer 497:524 Our studies were designed to investigate the expression and prognostic values of GalNAc-T5 and improve the risk stratification in patients with gastric cancer. 24619076 0 1 with patients 100:107 arg1 cancer 122:127 gastric cancer 114:127 gastric cancer 114:127 Clinical significance of polypeptide N-acetylgalactosaminyl transferase-5 (GalNAc-T5) expression in patients with gastric cancer. 24619076 11 2 theme Intratumoral 1691:1702 arg1 marker 1769:1774 an independent prognostic marker 1743:1774 an independent prognostic marker for the overall survival of gastric cancer patients 1743:1826 CONCLUSIONS Intratumoral GalNAc-T5 expression was recognised as an independent prognostic marker for the overall survival of gastric cancer patients. 24619076 11 2 theme Intratumoral 1691:1702 arg1 expression 1714:1723 Intratumoral GalNAc-T5 expression 1691:1723 Intratumoral GalNAc-T5 expression 1691:1723 CONCLUSIONS Intratumoral GalNAc-T5 expression was recognised as an independent prognostic marker for the overall survival of gastric cancer patients. 24619076 10 3 theme stage 1600:1604 arg1 system 1606:1611 the conventional clinicopathologic TNM stage system 1561:1611 the conventional clinicopathologic TNM stage system 1561:1611 Applying the prognostic value of intratumoral GalNAc-T5 density to the conventional clinicopathologic TNM stage system showed a better prognostic value in patients with gastric cancer. 24619076 3 4 theme gastric 608:614 arg1 adenocarcinoma 616:629 gastric adenocarcinoma 608:629 gastric adenocarcinoma from China 608:640 METHODS Tissue samples from a training set and a validation set of patients with gastric adenocarcinoma from China were used for analyses. 24619076 7 5 theme stratification 998:1011 arg1 scheme 1013:1018 A molecular prognostic stratification scheme 975:1018 A molecular prognostic stratification scheme incorporating GalNAc-T5 expression 975:1053 A molecular prognostic stratification scheme incorporating GalNAc-T5 expression was determined by using receiver operating characteristic analysis. 24619076 12 6 theme stage 2015:2019 arg1 system 2021:2026 the TNM stage system 2007:2026 the TNM stage system 2007:2026 Detection of GalNAc-T5 expression in gastric cancer tissues might add some prognostic information for patients with this disease and lead to a more accurate classification under the TNM stage system. 24619076 6 7 theme Cox 950:952 arg1 analysis 965:972 Cox regression analysis 950:972 Cox regression analysis 950:972 Prognostic values of GalNAc-T5 expression and clinical outcomes were evaluated by Cox regression analysis. 24619076 6 8 theme outcomes 923:930 arg1 values 879:884 Prognostic values 868:884 Prognostic values of GalNAc-T5 expression and clinical outcomes 868:930 Prognostic values of GalNAc-T5 expression and clinical outcomes were evaluated by Cox regression analysis. 24619076 3 9 theme patients 594:601 arg1 set 587:589 a validation set 574:589 a validation set of patients with gastric adenocarcinoma from China 574:640 METHODS Tissue samples from a training set and a validation set of patients with gastric adenocarcinoma from China were used for analyses. 24619076 3 9 theme patients 594:601 arg1 patients 594:601 patients 594:601 patients with gastric adenocarcinoma from China 594:640 METHODS Tissue samples from a training set and a validation set of patients with gastric adenocarcinoma from China were used for analyses. 24619076 3 9 theme patients 594:601 arg1 samples 542:548 METHODS Tissue samples 527:548 METHODS Tissue samples from a training set 527:568 METHODS Tissue samples from a training set and a validation set of patients with gastric adenocarcinoma from China were used for analyses. 24619076 7 10 theme molecular 977:985 arg1 scheme 1013:1018 A molecular prognostic stratification scheme 975:1018 A molecular prognostic stratification scheme incorporating GalNAc-T5 expression 975:1053 A molecular prognostic stratification scheme incorporating GalNAc-T5 expression was determined by using receiver operating characteristic analysis. 24619076 8 11 theme cancer 1184:1189 arg1 tissues 1191:1197 gastric cancer tissues 1176:1197 gastric cancer tissues 1176:1197 RESULTS GalNAc-T5 expression was markedly reduced in gastric cancer tissues compared with non-malignant gastric mucosa. 24619076 10 12 theme better 1622:1627 arg1 value 1640:1644 a better prognostic value 1620:1644 a better prognostic value 1620:1644 Applying the prognostic value of intratumoral GalNAc-T5 density to the conventional clinicopathologic TNM stage system showed a better prognostic value in patients with gastric cancer. 24619076 1 13 theme altered 226:232 arg1 glycosylation 243:255 the altered O-linked glycosylation 222:255 the altered O-linked glycosylation occurring during the development of various cancers and their progression via altering O-glycan biosynthesis 222:364 BACKGROUND The family of polypeptide N-acetylgalactosaminyl transferases is responsible for the altered O-linked glycosylation occurring during the development of various cancers and their progression via altering O-glycan biosynthesis. 24619076 12 14 theme GalNAc-T5 1842:1850 arg1 expression 1852:1861 GalNAc-T5 expression 1842:1861 GalNAc-T5 expression 1842:1861 Detection of GalNAc-T5 expression in gastric cancer tissues might add some prognostic information for patients with this disease and lead to a more accurate classification under the TNM stage system. 24619076 9 15 theme TNM 1374:1376 arg1 stage 1378:1382 TNM stage 1374:1382 TNM stage 1374:1382 Low intratumoral GalNAc-T5 density, which was associated with tumour cell differentiation, T classification, N classification, and TNM stage in the two independent sets, was an independent prognosticator for poor prognosis of gastric cancer patients. 24619076 9 16 from classification 1336:1349 arg1 sets 1407:1410 the two independent sets 1387:1410 the two independent sets 1387:1410 Low intratumoral GalNAc-T5 density, which was associated with tumour cell differentiation, T classification, N classification, and TNM stage in the two independent sets, was an independent prognosticator for poor prognosis of gastric cancer patients. 24619076 11 17 theme prognostic 1758:1767 arg1 marker 1769:1774 an independent prognostic marker 1743:1774 an independent prognostic marker for the overall survival of gastric cancer patients 1743:1826 CONCLUSIONS Intratumoral GalNAc-T5 expression was recognised as an independent prognostic marker for the overall survival of gastric cancer patients. 24619076 11 17 theme prognostic 1758:1767 arg1 expression 1714:1723 Intratumoral GalNAc-T5 expression 1691:1723 Intratumoral GalNAc-T5 expression 1691:1723 CONCLUSIONS Intratumoral GalNAc-T5 expression was recognised as an independent prognostic marker for the overall survival of gastric cancer patients. 24619076 5 18 theme overall 819:825 arg1 survival 827:834 overall survival 819:834 overall survival 819:834 Results were assessed for association with clinicopathological parameters and overall survival by using Kaplan-Meier analysis. 24619076 9 19 theme independent 1420:1430 arg1 prognosticator 1432:1445 an independent prognosticator 1417:1445 an independent prognosticator for poor prognosis of gastric cancer patients 1417:1491 Low intratumoral GalNAc-T5 density, which was associated with tumour cell differentiation, T classification, N classification, and TNM stage in the two independent sets, was an independent prognosticator for poor prognosis of gastric cancer patients. 24619076 9 19 theme independent 1420:1430 arg1 density 1270:1276 Low intratumoral GalNAc-T5 density 1243:1276 Low intratumoral GalNAc-T5 density 1243:1276 Low intratumoral GalNAc-T5 density, which was associated with tumour cell differentiation, T classification, N classification, and TNM stage in the two independent sets, was an independent prognosticator for poor prognosis of gastric cancer patients. 24619076 10 20 theme prognostic 1507:1516 arg1 value 1518:1522 the prognostic value 1503:1522 the prognostic value of intratumoral GalNAc-T5 density 1503:1556 Applying the prognostic value of intratumoral GalNAc-T5 density to the conventional clinicopathologic TNM stage system showed a better prognostic value in patients with gastric cancer. 24619076 9 21 theme gastric 1469:1475 arg1 patients 1484:1491 gastric cancer patients 1469:1491 gastric cancer patients 1469:1491 Low intratumoral GalNAc-T5 density, which was associated with tumour cell differentiation, T classification, N classification, and TNM stage in the two independent sets, was an independent prognosticator for poor prognosis of gastric cancer patients. 24619076 1 22 theme N-acetylgalactosaminyl 167:188 arg1 transferases 190:201 polypeptide N-acetylgalactosaminyl transferases 155:201 polypeptide N-acetylgalactosaminyl transferases 155:201 BACKGROUND The family of polypeptide N-acetylgalactosaminyl transferases is responsible for the altered O-linked glycosylation occurring during the development of various cancers and their progression via altering O-glycan biosynthesis. 24619076 10 23 theme gastric 1663:1669 arg1 cancer 1671:1676 gastric cancer 1663:1676 gastric cancer 1663:1676 Applying the prognostic value of intratumoral GalNAc-T5 density to the conventional clinicopathologic TNM stage system showed a better prognostic value in patients with gastric cancer. 24619076 9 24 theme intratumoral 1247:1258 arg1 prognosticator 1432:1445 an independent prognosticator 1417:1445 an independent prognosticator for poor prognosis of gastric cancer patients 1417:1491 Low intratumoral GalNAc-T5 density, which was associated with tumour cell differentiation, T classification, N classification, and TNM stage in the two independent sets, was an independent prognosticator for poor prognosis of gastric cancer patients. 24619076 9 24 theme intratumoral 1247:1258 arg1 density 1270:1276 Low intratumoral GalNAc-T5 density 1243:1276 Low intratumoral GalNAc-T5 density 1243:1276 Low intratumoral GalNAc-T5 density, which was associated with tumour cell differentiation, T classification, N classification, and TNM stage in the two independent sets, was an independent prognosticator for poor prognosis of gastric cancer patients. 24619076 9 25 theme patients 1484:1491 arg1 prognosis 1456:1464 poor prognosis 1451:1464 poor prognosis of gastric cancer patients 1451:1491 Low intratumoral GalNAc-T5 density, which was associated with tumour cell differentiation, T classification, N classification, and TNM stage in the two independent sets, was an independent prognosticator for poor prognosis of gastric cancer patients. 24619076 8 26 theme non-malignant 1213:1225 arg1 mucosa 1235:1240 non-malignant gastric mucosa 1213:1240 non-malignant gastric mucosa 1213:1240 RESULTS GalNAc-T5 expression was markedly reduced in gastric cancer tissues compared with non-malignant gastric mucosa. 24619076 1 27 link O-linked 234:241 arg1 glycosylation 243:255 the altered O-linked glycosylation 222:255 the altered O-linked glycosylation occurring during the development of various cancers and their progression via altering O-glycan biosynthesis 222:364 BACKGROUND The family of polypeptide N-acetylgalactosaminyl transferases is responsible for the altered O-linked glycosylation occurring during the development of various cancers and their progression via altering O-glycan biosynthesis. 24619076 5 28 theme Kaplan-Meier 845:856 arg1 analysis 858:865 Kaplan-Meier analysis 845:865 Kaplan-Meier analysis 845:865 Results were assessed for association with clinicopathological parameters and overall survival by using Kaplan-Meier analysis. 24619076 10 29 with patients 1649:1656 arg1 cancer 1671:1676 gastric cancer 1663:1676 gastric cancer 1663:1676 Applying the prognostic value of intratumoral GalNAc-T5 density to the conventional clinicopathologic TNM stage system showed a better prognostic value in patients with gastric cancer. 24619076 1 30 dep BACKGROUND 130:139 arg1 family 145:150 The family 141:150 The family of polypeptide N-acetylgalactosaminyl transferases 141:201 BACKGROUND The family of polypeptide N-acetylgalactosaminyl transferases is responsible for the altered O-linked glycosylation occurring during the development of various cancers and their progression via altering O-glycan biosynthesis. 24619076 1 30 dep BACKGROUND 130:139 arg1 responsible 206:216 responsible 206:216 responsible 206:216 BACKGROUND The family of polypeptide N-acetylgalactosaminyl transferases is responsible for the altered O-linked glycosylation occurring during the development of various cancers and their progression via altering O-glycan biosynthesis. 24619076 11 31 theme GalNAc-T5 1704:1712 arg1 marker 1769:1774 an independent prognostic marker 1743:1774 an independent prognostic marker for the overall survival of gastric cancer patients 1743:1826 CONCLUSIONS Intratumoral GalNAc-T5 expression was recognised as an independent prognostic marker for the overall survival of gastric cancer patients. 24619076 11 31 theme GalNAc-T5 1704:1712 arg1 expression 1714:1723 Intratumoral GalNAc-T5 expression 1691:1723 Intratumoral GalNAc-T5 expression 1691:1723 CONCLUSIONS Intratumoral GalNAc-T5 expression was recognised as an independent prognostic marker for the overall survival of gastric cancer patients. 24619076 2 32 theme GalNAc-T5 448:456 arg1 expression 412:421 expression 412:421 expression 412:421 Our studies were designed to investigate the expression and prognostic values of GalNAc-T5 and improve the risk stratification in patients with gastric cancer. 24619076 2 32 theme GalNAc-T5 448:456 arg1 values 438:443 prognostic values 427:443 prognostic values 427:443 Our studies were designed to investigate the expression and prognostic values of GalNAc-T5 and improve the risk stratification in patients with gastric cancer. 24619076 0 33 theme Clinical 0:7 arg1 significance 9:20 Clinical significance 0:20 Clinical significance of polypeptide N-acetylgalactosaminyl transferase-5 (GalNAc-T5) expression in patients with gastric cancer 0:127 Clinical significance of polypeptide N-acetylgalactosaminyl transferase-5 (GalNAc-T5) expression in patients with gastric cancer. 24619076 11 34 theme cancer 1812:1817 arg1 patients 1819:1826 gastric cancer patients 1804:1826 gastric cancer patients 1804:1826 CONCLUSIONS Intratumoral GalNAc-T5 expression was recognised as an independent prognostic marker for the overall survival of gastric cancer patients. 24619076 9 35 theme tumour 1305:1310 arg1 differentiation 1317:1331 tumour cell differentiation 1305:1331 tumour cell differentiation 1305:1331 Low intratumoral GalNAc-T5 density, which was associated with tumour cell differentiation, T classification, N classification, and TNM stage in the two independent sets, was an independent prognosticator for poor prognosis of gastric cancer patients. 24619076 3 36 theme Tissue 535:540 arg1 samples 542:548 METHODS Tissue samples 527:548 METHODS Tissue samples from a training set 527:568 METHODS Tissue samples from a training set and a validation set of patients with gastric adenocarcinoma from China were used for analyses. 24619076 1 37 theme O-glycan 344:351 arg1 biosynthesis 353:364 O-glycan biosynthesis 344:364 O-glycan biosynthesis 344:364 BACKGROUND The family of polypeptide N-acetylgalactosaminyl transferases is responsible for the altered O-linked glycosylation occurring during the development of various cancers and their progression via altering O-glycan biosynthesis. 24619076 12 38 with patients 1931:1938 arg1 disease 1950:1956 this disease 1945:1956 this disease 1945:1956 Detection of GalNAc-T5 expression in gastric cancer tissues might add some prognostic information for patients with this disease and lead to a more accurate classification under the TNM stage system. 24619076 2 39 theme risk 474:477 arg1 stratification 479:492 the risk stratification 470:492 the risk stratification in patients with gastric cancer 470:524 Our studies were designed to investigate the expression and prognostic values of GalNAc-T5 and improve the risk stratification in patients with gastric cancer. 24619076 0 40 theme N-acetylgalactosaminyl 37:58 arg1 expression 86:95 polypeptide N-acetylgalactosaminyl transferase-5 (GalNAc-T5) expression 25:95 polypeptide N-acetylgalactosaminyl transferase-5 (GalNAc-T5) expression in patients with gastric cancer 25:127 Clinical significance of polypeptide N-acetylgalactosaminyl transferase-5 (GalNAc-T5) expression in patients with gastric cancer. 24619076 3 41 with patients 594:601 arg1 adenocarcinoma 616:629 gastric adenocarcinoma 608:629 gastric adenocarcinoma from China 608:640 METHODS Tissue samples from a training set and a validation set of patients with gastric adenocarcinoma from China were used for analyses. 24619076 10 42 theme GalNAc-T5 1540:1548 arg1 density 1550:1556 intratumoral GalNAc-T5 density 1527:1556 intratumoral GalNAc-T5 density 1527:1556 Applying the prognostic value of intratumoral GalNAc-T5 density to the conventional clinicopathologic TNM stage system showed a better prognostic value in patients with gastric cancer. 24619076 3 43 theme training 557:564 arg1 set 566:568 a training set 555:568 a training set 555:568 METHODS Tissue samples from a training set and a validation set of patients with gastric adenocarcinoma from China were used for analyses. 24619076 12 44 from Detection 1829:1837 arg1 tissues 1881:1887 gastric cancer tissues 1866:1887 gastric cancer tissues 1866:1887 Detection of GalNAc-T5 expression in gastric cancer tissues might add some prognostic information for patients with this disease and lead to a more accurate classification under the TNM stage system. 24619076 11 45 theme gastric 1804:1810 arg1 patients 1819:1826 gastric cancer patients 1804:1826 gastric cancer patients 1804:1826 CONCLUSIONS Intratumoral GalNAc-T5 expression was recognised as an independent prognostic marker for the overall survival of gastric cancer patients. 24619076 6 46 theme Prognostic 868:877 arg1 values 879:884 Prognostic values 868:884 Prognostic values of GalNAc-T5 expression and clinical outcomes 868:930 Prognostic values of GalNAc-T5 expression and clinical outcomes were evaluated by Cox regression analysis. 24619076 10 47 theme density 1550:1556 arg1 value 1518:1522 the prognostic value 1503:1522 the prognostic value of intratumoral GalNAc-T5 density 1503:1556 Applying the prognostic value of intratumoral GalNAc-T5 density to the conventional clinicopathologic TNM stage system showed a better prognostic value in patients with gastric cancer. 24619076 8 48 theme GalNAc-T5 1131:1139 arg1 expression 1141:1150 RESULTS GalNAc-T5 expression 1123:1150 RESULTS GalNAc-T5 expression 1123:1150 RESULTS GalNAc-T5 expression was markedly reduced in gastric cancer tissues compared with non-malignant gastric mucosa. 24619076 4 49 theme GalNAc-T5 666:674 arg1 expression 676:685 GalNAc-T5 expression 666:685 GalNAc-T5 expression 666:685 GalNAc-T5 expression was retrospectively analysed by immunohistochemistry. 24619076 10 50 theme conventional 1565:1576 arg1 system 1606:1611 the conventional clinicopathologic TNM stage system 1561:1611 the conventional clinicopathologic TNM stage system 1561:1611 Applying the prognostic value of intratumoral GalNAc-T5 density to the conventional clinicopathologic TNM stage system showed a better prognostic value in patients with gastric cancer. 24619076 3 51 theme validation 576:585 arg1 patients 594:601 patients 594:601 patients with gastric adenocarcinoma from China 594:640 METHODS Tissue samples from a training set and a validation set of patients with gastric adenocarcinoma from China were used for analyses. 24619076 3 51 theme validation 576:585 arg1 set 587:589 a validation set 574:589 a validation set of patients with gastric adenocarcinoma from China 574:640 METHODS Tissue samples from a training set and a validation set of patients with gastric adenocarcinoma from China were used for analyses. 24619076 1 52 theme cancers 301:307 arg1 development 278:288 the development 274:288 the development of various cancers 274:307 BACKGROUND The family of polypeptide N-acetylgalactosaminyl transferases is responsible for the altered O-linked glycosylation occurring during the development of various cancers and their progression via altering O-glycan biosynthesis. 24619076 1 52 theme cancers 301:307 arg1 progression 319:329 their progression 313:329 their progression via altering O-glycan biosynthesis 313:364 BACKGROUND The family of polypeptide N-acetylgalactosaminyl transferases is responsible for the altered O-linked glycosylation occurring during the development of various cancers and their progression via altering O-glycan biosynthesis. 24619076 12 53 theme TNM 2011:2013 arg1 system 2021:2026 the TNM stage system 2007:2026 the TNM stage system 2007:2026 Detection of GalNAc-T5 expression in gastric cancer tissues might add some prognostic information for patients with this disease and lead to a more accurate classification under the TNM stage system. 24619076 6 54 theme clinical 914:921 arg1 outcomes 923:930 clinical outcomes 914:930 clinical outcomes 914:930 Prognostic values of GalNAc-T5 expression and clinical outcomes were evaluated by Cox regression analysis. 24619076 11 55 theme overall 1784:1790 arg1 survival 1792:1799 the overall survival 1780:1799 the overall survival of gastric cancer patients 1780:1826 CONCLUSIONS Intratumoral GalNAc-T5 expression was recognised as an independent prognostic marker for the overall survival of gastric cancer patients. 24619076 7 56 theme GalNAc-T5 1034:1042 arg1 expression 1044:1053 GalNAc-T5 expression 1034:1053 GalNAc-T5 expression 1034:1053 A molecular prognostic stratification scheme incorporating GalNAc-T5 expression was determined by using receiver operating characteristic analysis. 24619076 9 57 theme T 1334:1334 arg1 classification 1336:1349 T classification 1334:1349 T classification 1334:1349 Low intratumoral GalNAc-T5 density, which was associated with tumour cell differentiation, T classification, N classification, and TNM stage in the two independent sets, was an independent prognosticator for poor prognosis of gastric cancer patients. 24619076 8 58 theme gastric 1176:1182 arg1 tissues 1191:1197 gastric cancer tissues 1176:1197 gastric cancer tissues 1176:1197 RESULTS GalNAc-T5 expression was markedly reduced in gastric cancer tissues compared with non-malignant gastric mucosa. 24619076 10 59 theme TNM 1596:1598 arg1 system 1606:1611 the conventional clinicopathologic TNM stage system 1561:1611 the conventional clinicopathologic TNM stage system 1561:1611 Applying the prognostic value of intratumoral GalNAc-T5 density to the conventional clinicopathologic TNM stage system showed a better prognostic value in patients with gastric cancer. 24619076 12 60 theme accurate 1977:1984 arg1 classification 1986:1999 a more accurate classification 1970:1999 a more accurate classification under the TNM stage system 1970:2026 Detection of GalNAc-T5 expression in gastric cancer tissues might add some prognostic information for patients with this disease and lead to a more accurate classification under the TNM stage system. 24619076 9 61 theme independent 1395:1405 arg1 sets 1407:1410 the two independent sets 1387:1410 the two independent sets 1387:1410 Low intratumoral GalNAc-T5 density, which was associated with tumour cell differentiation, T classification, N classification, and TNM stage in the two independent sets, was an independent prognosticator for poor prognosis of gastric cancer patients. 24619076 7 62 theme prognostic 987:996 arg1 scheme 1013:1018 A molecular prognostic stratification scheme 975:1018 A molecular prognostic stratification scheme incorporating GalNAc-T5 expression 975:1053 A molecular prognostic stratification scheme incorporating GalNAc-T5 expression was determined by using receiver operating characteristic analysis. 24619076 12 63 theme expression 1852:1861 arg1 Detection 1829:1837 Detection 1829:1837 Detection of GalNAc-T5 expression in gastric cancer tissues 1829:1887 Detection of GalNAc-T5 expression in gastric cancer tissues might add some prognostic information for patients with this disease and lead to a more accurate classification under the TNM stage system. 24619076 9 64 from classification 1354:1367 arg1 sets 1407:1410 the two independent sets 1387:1410 the two independent sets 1387:1410 Low intratumoral GalNAc-T5 density, which was associated with tumour cell differentiation, T classification, N classification, and TNM stage in the two independent sets, was an independent prognosticator for poor prognosis of gastric cancer patients. 24619076 3 65 from set 566:568 arg1 set 587:589 a validation set 574:589 a validation set of patients with gastric adenocarcinoma from China 574:640 METHODS Tissue samples from a training set and a validation set of patients with gastric adenocarcinoma from China were used for analyses. 24619076 3 65 from set 566:568 arg1 patients 594:601 patients 594:601 patients with gastric adenocarcinoma from China 594:640 METHODS Tissue samples from a training set and a validation set of patients with gastric adenocarcinoma from China were used for analyses. 24619076 3 65 from set 566:568 arg1 samples 542:548 METHODS Tissue samples 527:548 METHODS Tissue samples from a training set 527:568 METHODS Tissue samples from a training set and a validation set of patients with gastric adenocarcinoma from China were used for analyses. 24619076 1 66 theme O-linked 234:241 arg1 glycosylation 243:255 the altered O-linked glycosylation 222:255 the altered O-linked glycosylation occurring during the development of various cancers and their progression via altering O-glycan biosynthesis 222:364 BACKGROUND The family of polypeptide N-acetylgalactosaminyl transferases is responsible for the altered O-linked glycosylation occurring during the development of various cancers and their progression via altering O-glycan biosynthesis. 24619076 12 67 theme gastric 1866:1872 arg1 tissues 1881:1887 gastric cancer tissues 1866:1887 gastric cancer tissues 1866:1887 Detection of GalNAc-T5 expression in gastric cancer tissues might add some prognostic information for patients with this disease and lead to a more accurate classification under the TNM stage system. 24619076 11 68 theme patients 1819:1826 arg1 survival 1792:1799 the overall survival 1780:1799 the overall survival of gastric cancer patients 1780:1826 CONCLUSIONS Intratumoral GalNAc-T5 expression was recognised as an independent prognostic marker for the overall survival of gastric cancer patients. 24619076 0 69 from patients 100:107 arg1 significance 9:20 Clinical significance 0:20 Clinical significance of polypeptide N-acetylgalactosaminyl transferase-5 (GalNAc-T5) expression in patients with gastric cancer 0:127 Clinical significance of polypeptide N-acetylgalactosaminyl transferase-5 (GalNAc-T5) expression in patients with gastric cancer. 24619076 0 70 from expression 86:95 arg1 patients 100:107 patients 100:107 patients with gastric cancer 100:127 Clinical significance of polypeptide N-acetylgalactosaminyl transferase-5 (GalNAc-T5) expression in patients with gastric cancer. 24619076 2 71 with patients 497:504 arg1 cancer 519:524 gastric cancer 511:524 gastric cancer 511:524 Our studies were designed to investigate the expression and prognostic values of GalNAc-T5 and improve the risk stratification in patients with gastric cancer. 24619076 3 72 used used 647:650 arg2 samples 542:548 METHODS Tissue samples 527:548 METHODS Tissue samples from a training set 527:568 METHODS Tissue samples from a training set and a validation set of patients with gastric adenocarcinoma from China were used for analyses. 24619076 3 72 used used 647:650 arg2 set 587:589 a validation set 574:589 a validation set of patients with gastric adenocarcinoma from China 574:640 METHODS Tissue samples from a training set and a validation set of patients with gastric adenocarcinoma from China were used for analyses. 24619076 3 72 used used 647:650 arg2 patients 594:601 patients 594:601 patients with gastric adenocarcinoma from China 594:640 METHODS Tissue samples from a training set and a validation set of patients with gastric adenocarcinoma from China were used for analyses. 24619076 6 73 theme expression 899:908 arg1 values 879:884 Prognostic values 868:884 Prognostic values of GalNAc-T5 expression and clinical outcomes 868:930 Prognostic values of GalNAc-T5 expression and clinical outcomes were evaluated by Cox regression analysis. 24619076 5 74 theme clinicopathological 784:802 arg1 parameters 804:813 clinicopathological parameters 784:813 clinicopathological parameters 784:813 Results were assessed for association with clinicopathological parameters and overall survival by using Kaplan-Meier analysis. 24619076 9 75 theme poor 1451:1454 arg1 prognosis 1456:1464 poor prognosis 1451:1464 poor prognosis of gastric cancer patients 1451:1491 Low intratumoral GalNAc-T5 density, which was associated with tumour cell differentiation, T classification, N classification, and TNM stage in the two independent sets, was an independent prognosticator for poor prognosis of gastric cancer patients. 24619076 3 76 from China 636:640 arg1 adenocarcinoma 616:629 gastric adenocarcinoma 608:629 gastric adenocarcinoma from China 608:640 METHODS Tissue samples from a training set and a validation set of patients with gastric adenocarcinoma from China were used for analyses. 24619076 0 77 theme expression 86:95 arg1 significance 9:20 Clinical significance 0:20 Clinical significance of polypeptide N-acetylgalactosaminyl transferase-5 (GalNAc-T5) expression in patients with gastric cancer 0:127 Clinical significance of polypeptide N-acetylgalactosaminyl transferase-5 (GalNAc-T5) expression in patients with gastric cancer. 24619076 1 78 theme polypeptide 155:165 arg1 transferases 190:201 polypeptide N-acetylgalactosaminyl transferases 155:201 polypeptide N-acetylgalactosaminyl transferases 155:201 BACKGROUND The family of polypeptide N-acetylgalactosaminyl transferases is responsible for the altered O-linked glycosylation occurring during the development of various cancers and their progression via altering O-glycan biosynthesis. 24619076 11 79 dep CONCLUSIONS 1679:1689 arg1 recognised 1729:1738 recognised 1729:1738 was recognised as an independent prognostic marker for the overall survival of gastric cancer patients 1725:1826 CONCLUSIONS Intratumoral GalNAc-T5 expression was recognised as an independent prognostic marker for the overall survival of gastric cancer patients. 24619076 9 80 theme Low 1243:1245 arg1 prognosticator 1432:1445 an independent prognosticator 1417:1445 an independent prognosticator for poor prognosis of gastric cancer patients 1417:1491 Low intratumoral GalNAc-T5 density, which was associated with tumour cell differentiation, T classification, N classification, and TNM stage in the two independent sets, was an independent prognosticator for poor prognosis of gastric cancer patients. 24619076 9 80 theme Low 1243:1245 arg1 density 1270:1276 Low intratumoral GalNAc-T5 density 1243:1276 Low intratumoral GalNAc-T5 density 1243:1276 Low intratumoral GalNAc-T5 density, which was associated with tumour cell differentiation, T classification, N classification, and TNM stage in the two independent sets, was an independent prognosticator for poor prognosis of gastric cancer patients. 24619076 9 81 theme cancer 1477:1482 arg1 patients 1484:1491 gastric cancer patients 1469:1491 gastric cancer patients 1469:1491 Low intratumoral GalNAc-T5 density, which was associated with tumour cell differentiation, T classification, N classification, and TNM stage in the two independent sets, was an independent prognosticator for poor prognosis of gastric cancer patients. 24619076 8 82 theme gastric 1227:1233 arg1 mucosa 1235:1240 non-malignant gastric mucosa 1213:1240 non-malignant gastric mucosa 1213:1240 RESULTS GalNAc-T5 expression was markedly reduced in gastric cancer tissues compared with non-malignant gastric mucosa. 24619076 1 83 theme transferases 190:201 arg1 family 145:150 The family 141:150 The family of polypeptide N-acetylgalactosaminyl transferases 141:201 BACKGROUND The family of polypeptide N-acetylgalactosaminyl transferases is responsible for the altered O-linked glycosylation occurring during the development of various cancers and their progression via altering O-glycan biosynthesis. 24619076 1 83 theme transferases 190:201 arg1 responsible 206:216 responsible 206:216 responsible 206:216 BACKGROUND The family of polypeptide N-acetylgalactosaminyl transferases is responsible for the altered O-linked glycosylation occurring during the development of various cancers and their progression via altering O-glycan biosynthesis. 24619076 0 84 from significance 9:20 arg1 patients 100:107 patients 100:107 patients with gastric cancer 100:127 Clinical significance of polypeptide N-acetylgalactosaminyl transferase-5 (GalNAc-T5) expression in patients with gastric cancer. 24619076 9 85 from stage 1378:1382 arg1 sets 1407:1410 the two independent sets 1387:1410 the two independent sets 1387:1410 Low intratumoral GalNAc-T5 density, which was associated with tumour cell differentiation, T classification, N classification, and TNM stage in the two independent sets, was an independent prognosticator for poor prognosis of gastric cancer patients. 24619076 9 86 theme GalNAc-T5 1260:1268 arg1 prognosticator 1432:1445 an independent prognosticator 1417:1445 an independent prognosticator for poor prognosis of gastric cancer patients 1417:1491 Low intratumoral GalNAc-T5 density, which was associated with tumour cell differentiation, T classification, N classification, and TNM stage in the two independent sets, was an independent prognosticator for poor prognosis of gastric cancer patients. 24619076 9 86 theme GalNAc-T5 1260:1268 arg1 density 1270:1276 Low intratumoral GalNAc-T5 density 1243:1276 Low intratumoral GalNAc-T5 density 1243:1276 Low intratumoral GalNAc-T5 density, which was associated with tumour cell differentiation, T classification, N classification, and TNM stage in the two independent sets, was an independent prognosticator for poor prognosis of gastric cancer patients. 24619076 0 87 theme gastric 114:120 arg1 cancer 122:127 gastric cancer 114:127 gastric cancer 114:127 Clinical significance of polypeptide N-acetylgalactosaminyl transferase-5 (GalNAc-T5) expression in patients with gastric cancer. 24619076 10 88 theme clinicopathologic 1578:1594 arg1 system 1606:1611 the conventional clinicopathologic TNM stage system 1561:1611 the conventional clinicopathologic TNM stage system 1561:1611 Applying the prognostic value of intratumoral GalNAc-T5 density to the conventional clinicopathologic TNM stage system showed a better prognostic value in patients with gastric cancer. 24619076 2 89 dep expression 412:421 arg1 the 408:410 the 408:410 the 408:410 Our studies were designed to investigate the expression and prognostic values of GalNAc-T5 and improve the risk stratification in patients with gastric cancer. 24619076 12 90 theme prognostic 1904:1913 arg1 information 1915:1925 some prognostic information 1899:1925 some prognostic information for patients with this disease 1899:1956 Detection of GalNAc-T5 expression in gastric cancer tissues might add some prognostic information for patients with this disease and lead to a more accurate classification under the TNM stage system. 24619076 11 91 theme independent 1746:1756 arg1 marker 1769:1774 an independent prognostic marker 1743:1774 an independent prognostic marker for the overall survival of gastric cancer patients 1743:1826 CONCLUSIONS Intratumoral GalNAc-T5 expression was recognised as an independent prognostic marker for the overall survival of gastric cancer patients. 24619076 11 91 theme independent 1746:1756 arg1 expression 1714:1723 Intratumoral GalNAc-T5 expression 1691:1723 Intratumoral GalNAc-T5 expression 1691:1723 CONCLUSIONS Intratumoral GalNAc-T5 expression was recognised as an independent prognostic marker for the overall survival of gastric cancer patients. 24619076 5 92 with association 767:777 arg1 parameters 804:813 clinicopathological parameters 784:813 clinicopathological parameters 784:813 Results were assessed for association with clinicopathological parameters and overall survival by using Kaplan-Meier analysis. 24619076 5 92 with association 767:777 arg1 survival 827:834 overall survival 819:834 overall survival 819:834 Results were assessed for association with clinicopathological parameters and overall survival by using Kaplan-Meier analysis. 24619076 2 93 theme gastric 511:517 arg1 cancer 519:524 gastric cancer 511:524 gastric cancer 511:524 Our studies were designed to investigate the expression and prognostic values of GalNAc-T5 and improve the risk stratification in patients with gastric cancer. 24619076 0 94 theme polypeptide 25:35 arg1 expression 86:95 polypeptide N-acetylgalactosaminyl transferase-5 (GalNAc-T5) expression 25:95 polypeptide N-acetylgalactosaminyl transferase-5 (GalNAc-T5) expression in patients with gastric cancer 25:127 Clinical significance of polypeptide N-acetylgalactosaminyl transferase-5 (GalNAc-T5) expression in patients with gastric cancer. 24619076 7 95 theme characteristic 1098:1111 arg1 analysis 1113:1120 characteristic analysis 1098:1120 characteristic analysis 1098:1120 A molecular prognostic stratification scheme incorporating GalNAc-T5 expression was determined by using receiver operating characteristic analysis. 24619076 12 96 theme cancer 1874:1879 arg1 tissues 1881:1887 gastric cancer tissues 1866:1887 gastric cancer tissues 1866:1887 Detection of GalNAc-T5 expression in gastric cancer tissues might add some prognostic information for patients with this disease and lead to a more accurate classification under the TNM stage system. 24619076 9 97 theme cell 1312:1315 arg1 differentiation 1317:1331 tumour cell differentiation 1305:1331 tumour cell differentiation 1305:1331 Low intratumoral GalNAc-T5 density, which was associated with tumour cell differentiation, T classification, N classification, and TNM stage in the two independent sets, was an independent prognosticator for poor prognosis of gastric cancer patients. 24619076 10 98 theme prognostic 1629:1638 arg1 value 1640:1644 a better prognostic value 1620:1644 a better prognostic value 1620:1644 Applying the prognostic value of intratumoral GalNAc-T5 density to the conventional clinicopathologic TNM stage system showed a better prognostic value in patients with gastric cancer. 24619076 0 99 theme transferase-5 60:72 arg1 expression 86:95 polypeptide N-acetylgalactosaminyl transferase-5 (GalNAc-T5) expression 25:95 polypeptide N-acetylgalactosaminyl transferase-5 (GalNAc-T5) expression in patients with gastric cancer 25:127 Clinical significance of polypeptide N-acetylgalactosaminyl transferase-5 (GalNAc-T5) expression in patients with gastric cancer. 24619076 9 100 from differentiation 1317:1331 arg1 sets 1407:1410 the two independent sets 1387:1410 the two independent sets 1387:1410 Low intratumoral GalNAc-T5 density, which was associated with tumour cell differentiation, T classification, N classification, and TNM stage in the two independent sets, was an independent prognosticator for poor prognosis of gastric cancer patients. 24619076 6 101 theme GalNAc-T5 889:897 arg1 expression 899:908 GalNAc-T5 expression 889:908 GalNAc-T5 expression 889:908 Prognostic values of GalNAc-T5 expression and clinical outcomes were evaluated by Cox regression analysis. 24619076 3 102 theme METHODS 527:533 arg1 samples 542:548 METHODS Tissue samples 527:548 METHODS Tissue samples from a training set 527:568 METHODS Tissue samples from a training set and a validation set of patients with gastric adenocarcinoma from China were used for analyses. 24619076 0 103 theme GalNAc-T5 75:83 arg1 expression 86:95 polypeptide N-acetylgalactosaminyl transferase-5 (GalNAc-T5) expression 25:95 polypeptide N-acetylgalactosaminyl transferase-5 (GalNAc-T5) expression in patients with gastric cancer 25:127 Clinical significance of polypeptide N-acetylgalactosaminyl transferase-5 (GalNAc-T5) expression in patients with gastric cancer. 24619076 10 104 theme intratumoral 1527:1538 arg1 density 1550:1556 intratumoral GalNAc-T5 density 1527:1556 intratumoral GalNAc-T5 density 1527:1556 Applying the prognostic value of intratumoral GalNAc-T5 density to the conventional clinicopathologic TNM stage system showed a better prognostic value in patients with gastric cancer. 24619076 9 105 theme N 1352:1352 arg1 classification 1354:1367 N classification 1352:1367 N classification 1352:1367 Low intratumoral GalNAc-T5 density, which was associated with tumour cell differentiation, T classification, N classification, and TNM stage in the two independent sets, was an independent prognosticator for poor prognosis of gastric cancer patients. 24619076 6 106 theme regression 954:963 arg1 analysis 965:972 Cox regression analysis 950:972 Cox regression analysis 950:972 Prognostic values of GalNAc-T5 expression and clinical outcomes were evaluated by Cox regression analysis. 24619076 8 107 theme RESULTS 1123:1129 arg1 expression 1141:1150 RESULTS GalNAc-T5 expression 1123:1150 RESULTS GalNAc-T5 expression 1123:1150 RESULTS GalNAc-T5 expression was markedly reduced in gastric cancer tissues compared with non-malignant gastric mucosa. 24619076 2 108 theme prognostic 427:436 arg1 values 438:443 prognostic values 427:443 prognostic values 427:443 Our studies were designed to investigate the expression and prognostic values of GalNAc-T5 and improve the risk stratification in patients with gastric cancer. 24619076 1 109 theme various 293:299 arg1 cancers 301:307 various cancers 293:307 various cancers 293:307 BACKGROUND The family of polypeptide N-acetylgalactosaminyl transferases is responsible for the altered O-linked glycosylation occurring during the development of various cancers and their progression via altering O-glycan biosynthesis. 24326295 6 0 theme pathological 1019:1030 arg1 species 1036:1042 pathological tau species 1019:1042 pathological tau species 1019:1042 More importantly, long-term inhibitor treatment strongly increased tau O-GlcNAcylation, reduced the number of dystrophic neurons, and protected against the formation of pathological tau species without altering the phosphorylation of non-pathological tau. 24326295 8 1 dep potential 1303:1311 arg1 therapeutic 1313:1323 therapeutic 1313:1323 therapeutic 1313:1323 Collectively, our results support O-GlcNAcase inhibition as a potential therapeutic strategy for the treatment of Alzheimer's Disease and other tauopathies. 24326295 6 2 theme neurons 971:977 arg1 number 950:955 the number 946:955 the number of dystrophic neurons 946:977 More importantly, long-term inhibitor treatment strongly increased tau O-GlcNAcylation, reduced the number of dystrophic neurons, and protected against the formation of pathological tau species without altering the phosphorylation of non-pathological tau. 24326295 7 3 theme tau 1170:1172 arg1 aggregation 1155:1165 the aggregation 1151:1165 the aggregation of tau 1151:1172 This indicates that O-GlcNAcylation prevents the aggregation of tau in a manner that does not affect its normal phosphorylation state. 24326295 8 4 theme potential 1303:1311 arg1 strategy 1325:1332 a potential therapeutic strategy 1301:1332 a potential therapeutic strategy for the treatment of Alzheimer's Disease and other tauopathies 1301:1395 Collectively, our results support O-GlcNAcase inhibition as a potential therapeutic strategy for the treatment of Alzheimer's Disease and other tauopathies. 24326295 8 4 theme potential 1303:1311 arg1 inhibition 1287:1296 O-GlcNAcase inhibition 1275:1296 O-GlcNAcase inhibition 1275:1296 Collectively, our results support O-GlcNAcase inhibition as a potential therapeutic strategy for the treatment of Alzheimer's Disease and other tauopathies. 24326295 6 5 theme tau 917:919 arg1 O-GlcNAcylation 921:935 tau O-GlcNAcylation 917:935 tau O-GlcNAcylation 917:935 More importantly, long-term inhibitor treatment strongly increased tau O-GlcNAcylation, reduced the number of dystrophic neurons, and protected against the formation of pathological tau species without altering the phosphorylation of non-pathological tau. 24326295 5 6 theme O-GlcNAcase 747:757 arg1 inhibitor 759:767 an O-GlcNAcase inhibitor 744:767 an O-GlcNAcase inhibitor 744:767 Acute treatment of rTg4510 mice with an O-GlcNAcase inhibitor transiently reduced tau phosphorylation at epitopes implicated in tau pathology. 24326295 6 7 theme dystrophic 960:969 arg1 neurons 971:977 dystrophic neurons 960:977 dystrophic neurons 960:977 More importantly, long-term inhibitor treatment strongly increased tau O-GlcNAcylation, reduced the number of dystrophic neurons, and protected against the formation of pathological tau species without altering the phosphorylation of non-pathological tau. 24326295 0 8 theme mouse 101:105 arg1 model 107:111 a mouse model 99:111 a mouse model of tauopathy 99:124 Increased O-GlcNAcylation reduces pathological tau without affecting its normal phosphorylation in a mouse model of tauopathy. 24326295 4 9 theme tau 599:601 arg1 O-GlcNAcylation 603:617 tau O-GlcNAcylation 599:617 tau O-GlcNAcylation 599:617 We tested if an increase in tau O-GlcNAcylation affected tau phosphorylation and aggregation in the rTg4510 tau transgenic mouse model. 24326295 0 10 theme tauopathy 116:124 arg1 model 107:111 a mouse model 99:111 a mouse model of tauopathy 99:124 Increased O-GlcNAcylation reduces pathological tau without affecting its normal phosphorylation in a mouse model of tauopathy. 24326295 2 11 theme cellular 379:386 arg1 event 388:392 a toxic cellular event 371:392 a toxic cellular event causing neurodegeneration 371:418 Progressive accumulation of tau into NFT is considered to be a toxic cellular event causing neurodegeneration. 24326295 2 11 theme cellular 379:386 arg1 accumulation 322:333 Progressive accumulation 310:333 Progressive accumulation of tau into NFT 310:349 Progressive accumulation of tau into NFT is considered to be a toxic cellular event causing neurodegeneration. 24326295 3 12 theme O-linked 439:446 arg1 O-GlcNAc 469:476 O-GlcNAc 469:476 O-GlcNAc 469:476 Tau is subject to O-linked N-acetylglucosamine (O-GlcNAc) modification and O-GlcNAcylation of tau has been suggested to regulate tau phosphorylation. 24326295 3 12 theme O-linked 439:446 arg1 N-acetylglucosamine 448:466 O-linked N-acetylglucosamine 439:466 O-linked N-acetylglucosamine (O-GlcNAc) modification 439:490 Tau is subject to O-linked N-acetylglucosamine (O-GlcNAc) modification and O-GlcNAcylation of tau has been suggested to regulate tau phosphorylation. 24326295 4 13 from increase 587:594 arg1 O-GlcNAcylation 603:617 tau O-GlcNAcylation 599:617 tau O-GlcNAcylation 599:617 We tested if an increase in tau O-GlcNAcylation affected tau phosphorylation and aggregation in the rTg4510 tau transgenic mouse model. 24326295 3 14 theme tau 550:552 arg1 phosphorylation 554:568 tau phosphorylation 550:568 tau phosphorylation 550:568 Tau is subject to O-linked N-acetylglucosamine (O-GlcNAc) modification and O-GlcNAcylation of tau has been suggested to regulate tau phosphorylation. 24326295 3 15 theme N-acetylglucosamine 448:466 arg1 modification 479:490 O-linked N-acetylglucosamine (O-GlcNAc) modification 439:490 O-linked N-acetylglucosamine (O-GlcNAc) modification 439:490 Tau is subject to O-linked N-acetylglucosamine (O-GlcNAc) modification and O-GlcNAcylation of tau has been suggested to regulate tau phosphorylation. 24326295 3 16 link O-linked 439:446 arg1 O-GlcNAc 469:476 O-GlcNAc 469:476 O-GlcNAc 469:476 Tau is subject to O-linked N-acetylglucosamine (O-GlcNAc) modification and O-GlcNAcylation of tau has been suggested to regulate tau phosphorylation. 24326295 3 16 link O-linked 439:446 arg1 N-acetylglucosamine 448:466 O-linked N-acetylglucosamine 439:466 O-linked N-acetylglucosamine (O-GlcNAc) modification 439:490 Tau is subject to O-linked N-acetylglucosamine (O-GlcNAc) modification and O-GlcNAcylation of tau has been suggested to regulate tau phosphorylation. 24326295 1 17 theme fibrillar 179:187 arg1 aggregates 189:198 fibrillar aggregates 179:198 fibrillar aggregates of hyperphosphorylated tau 179:225 Neurofibrillary tangles (NFT), mainly consisting of fibrillar aggregates of hyperphosphorylated tau, are a defining pathological feature of Alzheimer's Disease and other tauopathies. 24326295 0 18 theme Increased 0:8 arg1 O-GlcNAcylation 10:24 Increased O-GlcNAcylation 0:24 Increased O-GlcNAcylation 0:24 Increased O-GlcNAcylation reduces pathological tau without affecting its normal phosphorylation in a mouse model of tauopathy. 24326295 6 19 theme species 1036:1042 arg1 formation 1006:1014 the formation 1002:1014 the formation of pathological tau species 1002:1042 More importantly, long-term inhibitor treatment strongly increased tau O-GlcNAcylation, reduced the number of dystrophic neurons, and protected against the formation of pathological tau species without altering the phosphorylation of non-pathological tau. 24326295 2 20 theme toxic 373:377 arg1 event 388:392 a toxic cellular event 371:392 a toxic cellular event causing neurodegeneration 371:418 Progressive accumulation of tau into NFT is considered to be a toxic cellular event causing neurodegeneration. 24326295 2 20 theme toxic 373:377 arg1 accumulation 322:333 Progressive accumulation 310:333 Progressive accumulation of tau into NFT 310:349 Progressive accumulation of tau into NFT is considered to be a toxic cellular event causing neurodegeneration. 24326295 0 21 theme pathological 34:45 arg1 tau 47:49 pathological tau 34:49 pathological tau 34:49 Increased O-GlcNAcylation reduces pathological tau without affecting its normal phosphorylation in a mouse model of tauopathy. 24326295 6 22 theme tau 1032:1034 arg1 species 1036:1042 pathological tau species 1019:1042 pathological tau species 1019:1042 More importantly, long-term inhibitor treatment strongly increased tau O-GlcNAcylation, reduced the number of dystrophic neurons, and protected against the formation of pathological tau species without altering the phosphorylation of non-pathological tau. 24326295 5 23 theme rTg4510 726:732 arg1 mice 734:737 rTg4510 mice 726:737 rTg4510 mice 726:737 Acute treatment of rTg4510 mice with an O-GlcNAcase inhibitor transiently reduced tau phosphorylation at epitopes implicated in tau pathology. 24326295 2 24 theme Progressive 310:320 arg1 event 388:392 a toxic cellular event 371:392 a toxic cellular event causing neurodegeneration 371:418 Progressive accumulation of tau into NFT is considered to be a toxic cellular event causing neurodegeneration. 24326295 2 24 theme Progressive 310:320 arg1 accumulation 322:333 Progressive accumulation 310:333 Progressive accumulation of tau into NFT 310:349 Progressive accumulation of tau into NFT is considered to be a toxic cellular event causing neurodegeneration. 24326295 8 25 theme O-GlcNAcase 1275:1285 arg1 strategy 1325:1332 a potential therapeutic strategy 1301:1332 a potential therapeutic strategy for the treatment of Alzheimer's Disease and other tauopathies 1301:1395 Collectively, our results support O-GlcNAcase inhibition as a potential therapeutic strategy for the treatment of Alzheimer's Disease and other tauopathies. 24326295 8 25 theme O-GlcNAcase 1275:1285 arg1 inhibition 1287:1296 O-GlcNAcase inhibition 1275:1296 O-GlcNAcase inhibition 1275:1296 Collectively, our results support O-GlcNAcase inhibition as a potential therapeutic strategy for the treatment of Alzheimer's Disease and other tauopathies. 24326295 1 26 theme other 291:295 arg1 tauopathies 297:307 other tauopathies 291:307 other tauopathies 291:307 Neurofibrillary tangles (NFT), mainly consisting of fibrillar aggregates of hyperphosphorylated tau, are a defining pathological feature of Alzheimer's Disease and other tauopathies. 24326295 5 27 theme mice 734:737 arg1 treatment 713:721 Acute treatment 707:721 Acute treatment of rTg4510 mice with an O-GlcNAcase inhibitor 707:767 Acute treatment of rTg4510 mice with an O-GlcNAcase inhibitor transiently reduced tau phosphorylation at epitopes implicated in tau pathology. 24326295 1 28 theme hyperphosphorylated 203:221 arg1 tau 223:225 hyperphosphorylated tau 203:225 hyperphosphorylated tau 203:225 Neurofibrillary tangles (NFT), mainly consisting of fibrillar aggregates of hyperphosphorylated tau, are a defining pathological feature of Alzheimer's Disease and other tauopathies. 24326295 7 29 theme phosphorylation 1218:1232 arg1 state 1234:1238 its normal phosphorylation state 1207:1238 its normal phosphorylation state 1207:1238 This indicates that O-GlcNAcylation prevents the aggregation of tau in a manner that does not affect its normal phosphorylation state. 24326295 3 30 theme tau 515:517 arg1 O-GlcNAcylation 496:510 O-GlcNAcylation 496:510 O-GlcNAcylation of tau 496:517 Tau is subject to O-linked N-acetylglucosamine (O-GlcNAc) modification and O-GlcNAcylation of tau has been suggested to regulate tau phosphorylation. 24326295 4 31 theme rTg4510 671:677 arg1 model 700:704 the rTg4510 tau transgenic mouse model 667:704 the rTg4510 tau transgenic mouse model 667:704 We tested if an increase in tau O-GlcNAcylation affected tau phosphorylation and aggregation in the rTg4510 tau transgenic mouse model. 24326295 4 32 theme mouse 694:698 arg1 model 700:704 the rTg4510 tau transgenic mouse model 667:704 the rTg4510 tau transgenic mouse model 667:704 We tested if an increase in tau O-GlcNAcylation affected tau phosphorylation and aggregation in the rTg4510 tau transgenic mouse model. 24326295 1 33 theme tau 223:225 arg1 aggregates 189:198 fibrillar aggregates 179:198 fibrillar aggregates of hyperphosphorylated tau 179:225 Neurofibrillary tangles (NFT), mainly consisting of fibrillar aggregates of hyperphosphorylated tau, are a defining pathological feature of Alzheimer's Disease and other tauopathies. 24326295 4 34 theme transgenic 683:692 arg1 model 700:704 the rTg4510 tau transgenic mouse model 667:704 the rTg4510 tau transgenic mouse model 667:704 We tested if an increase in tau O-GlcNAcylation affected tau phosphorylation and aggregation in the rTg4510 tau transgenic mouse model. 24326295 0 35 from phosphorylation 80:94 arg1 model 107:111 a mouse model 99:111 a mouse model of tauopathy 99:124 Increased O-GlcNAcylation reduces pathological tau without affecting its normal phosphorylation in a mouse model of tauopathy. 24326295 6 36 theme non-pathological 1084:1099 arg1 tau 1101:1103 non-pathological tau 1084:1103 non-pathological tau 1084:1103 More importantly, long-term inhibitor treatment strongly increased tau O-GlcNAcylation, reduced the number of dystrophic neurons, and protected against the formation of pathological tau species without altering the phosphorylation of non-pathological tau. 24326295 5 37 theme tau 835:837 arg1 pathology 839:847 tau pathology 835:847 tau pathology 835:847 Acute treatment of rTg4510 mice with an O-GlcNAcase inhibitor transiently reduced tau phosphorylation at epitopes implicated in tau pathology. 24326295 8 38 theme other 1379:1383 arg1 tauopathies 1385:1395 other tauopathies 1379:1395 other tauopathies 1379:1395 Collectively, our results support O-GlcNAcase inhibition as a potential therapeutic strategy for the treatment of Alzheimer's Disease and other tauopathies. 24326295 7 39 theme normal 1211:1216 arg1 state 1234:1238 its normal phosphorylation state 1207:1238 its normal phosphorylation state 1207:1238 This indicates that O-GlcNAcylation prevents the aggregation of tau in a manner that does not affect its normal phosphorylation state. 24326295 5 40 theme Acute 707:711 arg1 treatment 713:721 Acute treatment 707:721 Acute treatment of rTg4510 mice with an O-GlcNAcase inhibitor 707:767 Acute treatment of rTg4510 mice with an O-GlcNAcase inhibitor transiently reduced tau phosphorylation at epitopes implicated in tau pathology. 24326295 5 41 with treatment 713:721 arg1 inhibitor 759:767 an O-GlcNAcase inhibitor 744:767 an O-GlcNAcase inhibitor 744:767 Acute treatment of rTg4510 mice with an O-GlcNAcase inhibitor transiently reduced tau phosphorylation at epitopes implicated in tau pathology. 24326295 1 42 theme Neurofibrillary 127:141 arg1 tangles 143:149 Neurofibrillary tangles 127:149 Neurofibrillary tangles (NFT) 127:155 Neurofibrillary tangles (NFT), mainly consisting of fibrillar aggregates of hyperphosphorylated tau, are a defining pathological feature of Alzheimer's Disease and other tauopathies. 24326295 1 42 theme Neurofibrillary 127:141 arg1 feature 256:262 a defining pathological feature 232:262 a defining pathological feature of Alzheimer's Disease and other tauopathies 232:307 Neurofibrillary tangles (NFT), mainly consisting of fibrillar aggregates of hyperphosphorylated tau, are a defining pathological feature of Alzheimer's Disease and other tauopathies. 24326295 1 42 theme Neurofibrillary 127:141 arg1 NFT 152:154 NFT 152:154 NFT 152:154 Neurofibrillary tangles (NFT), mainly consisting of fibrillar aggregates of hyperphosphorylated tau, are a defining pathological feature of Alzheimer's Disease and other tauopathies. 24326295 4 43 theme tau 628:630 arg1 phosphorylation 632:646 tau phosphorylation 628:646 tau phosphorylation 628:646 We tested if an increase in tau O-GlcNAcylation affected tau phosphorylation and aggregation in the rTg4510 tau transgenic mouse model. 24326295 6 44 theme inhibitor 878:886 arg1 treatment 888:896 long-term inhibitor treatment 868:896 long-term inhibitor treatment 868:896 More importantly, long-term inhibitor treatment strongly increased tau O-GlcNAcylation, reduced the number of dystrophic neurons, and protected against the formation of pathological tau species without altering the phosphorylation of non-pathological tau. 24326295 2 45 theme tau 338:340 arg1 event 388:392 a toxic cellular event 371:392 a toxic cellular event causing neurodegeneration 371:418 Progressive accumulation of tau into NFT is considered to be a toxic cellular event causing neurodegeneration. 24326295 2 45 theme tau 338:340 arg1 accumulation 322:333 Progressive accumulation 310:333 Progressive accumulation of tau into NFT 310:349 Progressive accumulation of tau into NFT is considered to be a toxic cellular event causing neurodegeneration. 24326295 6 46 theme tau 1101:1103 arg1 phosphorylation 1065:1079 the phosphorylation 1061:1079 the phosphorylation of non-pathological tau 1061:1103 More importantly, long-term inhibitor treatment strongly increased tau O-GlcNAcylation, reduced the number of dystrophic neurons, and protected against the formation of pathological tau species without altering the phosphorylation of non-pathological tau. 24326295 5 47 theme tau 789:791 arg1 phosphorylation 793:807 tau phosphorylation 789:807 tau phosphorylation 789:807 Acute treatment of rTg4510 mice with an O-GlcNAcase inhibitor transiently reduced tau phosphorylation at epitopes implicated in tau pathology. 24326295 6 48 theme long-term 868:876 arg1 treatment 888:896 long-term inhibitor treatment 868:896 long-term inhibitor treatment 868:896 More importantly, long-term inhibitor treatment strongly increased tau O-GlcNAcylation, reduced the number of dystrophic neurons, and protected against the formation of pathological tau species without altering the phosphorylation of non-pathological tau. 24326295 4 49 theme tau 679:681 arg1 model 700:704 the rTg4510 tau transgenic mouse model 667:704 the rTg4510 tau transgenic mouse model 667:704 We tested if an increase in tau O-GlcNAcylation affected tau phosphorylation and aggregation in the rTg4510 tau transgenic mouse model. 24326295 1 50 theme defining 234:241 arg1 tangles 143:149 Neurofibrillary tangles 127:149 Neurofibrillary tangles (NFT) 127:155 Neurofibrillary tangles (NFT), mainly consisting of fibrillar aggregates of hyperphosphorylated tau, are a defining pathological feature of Alzheimer's Disease and other tauopathies. 24326295 1 50 theme defining 234:241 arg1 feature 256:262 a defining pathological feature 232:262 a defining pathological feature of Alzheimer's Disease and other tauopathies 232:307 Neurofibrillary tangles (NFT), mainly consisting of fibrillar aggregates of hyperphosphorylated tau, are a defining pathological feature of Alzheimer's Disease and other tauopathies. 24326295 0 51 theme normal 73:78 arg1 phosphorylation 80:94 its normal phosphorylation 69:94 its normal phosphorylation in a mouse model of tauopathy 69:124 Increased O-GlcNAcylation reduces pathological tau without affecting its normal phosphorylation in a mouse model of tauopathy. 24326295 1 52 theme pathological 243:254 arg1 tangles 143:149 Neurofibrillary tangles 127:149 Neurofibrillary tangles (NFT) 127:155 Neurofibrillary tangles (NFT), mainly consisting of fibrillar aggregates of hyperphosphorylated tau, are a defining pathological feature of Alzheimer's Disease and other tauopathies. 24326295 1 52 theme pathological 243:254 arg1 feature 256:262 a defining pathological feature 232:262 a defining pathological feature of Alzheimer's Disease and other tauopathies 232:307 Neurofibrillary tangles (NFT), mainly consisting of fibrillar aggregates of hyperphosphorylated tau, are a defining pathological feature of Alzheimer's Disease and other tauopathies. 28154008 0 0 theme Pathogen 64:71 arg1 capsulatum 85:94 the Fungal Pathogen Histoplasma capsulatum 53:94 the Fungal Pathogen Histoplasma capsulatum 53:94 Eng1 and Exg8 Are the Major β-Glucanases Secreted by the Fungal Pathogen Histoplasma capsulatum. 28154008 1 1 contain contain 115:121 arg1 walls 109:113 Fungal cell walls 97:113 Fungal cell walls 97:113 Fungal cell walls contain β-glucan polysaccharides that stimulate immune responses when recognized by host immune cells. 28154008 1 1 contain contain 115:121 arg2 polysaccharides 132:146 β-glucan polysaccharides 123:146 β-glucan polysaccharides that stimulate immune responses when recognized by host immune cells 123:215 Fungal cell walls contain β-glucan polysaccharides that stimulate immune responses when recognized by host immune cells. 28154008 4 2 theme Exg8 700:703 arg1 proteins 705:712 the Eng1 and Exg8 proteins 687:712 proteins 705:712 Here, we characterize the enzymatic specificity of the Eng1 and Exg8 proteins and show that Exg8 is an exo-β1,3-glucanase and Eng1 is an endo-β1,3-glucanase. 28154008 9 3 from dispensable 1396:1406 arg1 contrast 1434:1441 contrast 1434:1441 contrast to Eng1 1434:1449 Exg8 is largely dispensable for virulence in vivo, in contrast to Eng1. 28154008 2 4 theme beneath 365:371 arg1 α-glucans 373:381 β-glucans beneath α-glucans 355:381 β-glucans beneath α-glucans 355:381 The fungal pathogen Histoplasma capsulatum minimizes detection of β-glucan by host cells through at least two mechanisms: concealment of β-glucans beneath α-glucans and enzymatic removal of any exposed β-glucan polysaccharides by the secreted glucanase Eng1. 28154008 0 5 theme Fungal 57:62 arg1 capsulatum 85:94 the Fungal Pathogen Histoplasma capsulatum 53:94 the Fungal Pathogen Histoplasma capsulatum 53:94 Eng1 and Exg8 Are the Major β-Glucanases Secreted by the Fungal Pathogen Histoplasma capsulatum. 28154008 5 6 theme Histoplasma 885:895 arg1 yeasts 897:902 Histoplasma yeasts 885:902 Histoplasma yeasts 885:902 Together, Eng1 and Exg8 account for nearly all of the total secreted glucanase activity of Histoplasma yeasts. 28154008 1 7 theme immune 163:168 arg1 responses 170:178 immune responses 163:178 immune responses 163:178 Fungal cell walls contain β-glucan polysaccharides that stimulate immune responses when recognized by host immune cells. 28154008 10 8 theme predominant 1567:1577 arg1 factor 1579:1584 the predominant factor 1563:1584 the predominant factor responsible for removal of exposed cell wall β-glucans to minimize host detection of Histoplasma yeasts 1563:1688 These results show that Histoplasma yeasts secrete two β1,3-glucanases and that Eng1 endoglucanase activity is the predominant factor responsible for removal of exposed cell wall β-glucans to minimize host detection of Histoplasma yeasts. 28154008 10 8 theme predominant 1567:1577 arg1 activity 1551:1558 Eng1 endoglucanase activity 1532:1558 Eng1 endoglucanase activity 1532:1558 These results show that Histoplasma yeasts secrete two β1,3-glucanases and that Eng1 endoglucanase activity is the predominant factor responsible for removal of exposed cell wall β-glucans to minimize host detection of Histoplasma yeasts. 28154008 3 9 theme Histoplasma 477:487 arg1 yeasts 489:494 Histoplasma yeasts 477:494 Histoplasma yeasts 477:494 Histoplasma yeasts also secrete the putative glucanase Exg8, which may serve a similar role as Eng1 in removing exposed β-glucans from the yeast cell surface. 28154008 2 10 theme β-glucans 355:363 arg1 α-glucans 373:381 β-glucans beneath α-glucans 355:381 β-glucans beneath α-glucans 355:381 The fungal pathogen Histoplasma capsulatum minimizes detection of β-glucan by host cells through at least two mechanisms: concealment of β-glucans beneath α-glucans and enzymatic removal of any exposed β-glucan polysaccharides by the secreted glucanase Eng1. 28154008 3 11 theme exposed 589:595 arg1 β-glucans 597:605 exposed β-glucans 589:605 exposed β-glucans 589:605 Histoplasma yeasts also secrete the putative glucanase Exg8, which may serve a similar role as Eng1 in removing exposed β-glucans from the yeast cell surface. 28154008 3 12 theme similar 556:562 arg1 role 564:567 a similar role 554:567 a similar role 554:567 Histoplasma yeasts also secrete the putative glucanase Exg8, which may serve a similar role as Eng1 in removing exposed β-glucans from the yeast cell surface. 28154008 10 13 theme wall 1626:1629 arg1 β-glucans 1631:1639 exposed cell wall β-glucans 1613:1639 exposed cell wall β-glucans 1613:1639 These results show that Histoplasma yeasts secrete two β1,3-glucanases and that Eng1 endoglucanase activity is the predominant factor responsible for removal of exposed cell wall β-glucans to minimize host detection of Histoplasma yeasts. 28154008 0 14 theme Histoplasma 73:83 arg1 capsulatum 85:94 the Fungal Pathogen Histoplasma capsulatum 53:94 the Fungal Pathogen Histoplasma capsulatum 53:94 Eng1 and Exg8 Are the Major β-Glucanases Secreted by the Fungal Pathogen Histoplasma capsulatum. 28154008 2 15 theme host 296:299 arg1 cells 301:305 host cells 296:305 host cells 296:305 The fungal pathogen Histoplasma capsulatum minimizes detection of β-glucan by host cells through at least two mechanisms: concealment of β-glucans beneath α-glucans and enzymatic removal of any exposed β-glucan polysaccharides by the secreted glucanase Eng1. 28154008 3 16 attach removing 580:587 arg2 Eng1 572:575 Eng1 572:575 Eng1 in removing exposed β-glucans from the yeast cell surface 572:633 Histoplasma yeasts also secrete the putative glucanase Exg8, which may serve a similar role as Eng1 in removing exposed β-glucans from the yeast cell surface. 28154008 3 16 attach removing 580:587 arg1 surface 627:633 the yeast cell surface 612:633 the yeast cell surface 612:633 Histoplasma yeasts also secrete the putative glucanase Exg8, which may serve a similar role as Eng1 in removing exposed β-glucans from the yeast cell surface. 28154008 10 17 theme cell 1621:1624 arg1 β-glucans 1631:1639 exposed cell wall β-glucans 1613:1639 exposed cell wall β-glucans 1613:1639 These results show that Histoplasma yeasts secrete two β1,3-glucanases and that Eng1 endoglucanase activity is the predominant factor responsible for removal of exposed cell wall β-glucans to minimize host detection of Histoplasma yeasts. 28154008 3 18 theme putative 513:520 arg1 Exg8 532:535 the putative glucanase Exg8 509:535 the putative glucanase Exg8 509:535 Histoplasma yeasts also secrete the putative glucanase Exg8, which may serve a similar role as Eng1 in removing exposed β-glucans from the yeast cell surface. 28154008 7 19 theme pH 1113:1114 arg1 conditions 1116:1125 temperature and pH conditions 1097:1125 conditions 1116:1125 Both glucanases have near maximal activity at temperature and pH conditions experienced during infection of host cells, supporting roles in Histoplasma pathogenesis. 28154008 2 20 theme polysaccharides 429:443 arg1 concealment 340:350 concealment 340:350 concealment of β-glucans beneath α-glucans 340:381 The fungal pathogen Histoplasma capsulatum minimizes detection of β-glucan by host cells through at least two mechanisms: concealment of β-glucans beneath α-glucans and enzymatic removal of any exposed β-glucan polysaccharides by the secreted glucanase Eng1. 28154008 2 20 theme polysaccharides 429:443 arg1 mechanisms 328:337 at least two mechanisms 315:337 at least two mechanisms: concealment of β-glucans beneath α-glucans and enzymatic removal of any exposed β-glucan polysaccharides 315:443 The fungal pathogen Histoplasma capsulatum minimizes detection of β-glucan by host cells through at least two mechanisms: concealment of β-glucans beneath α-glucans and enzymatic removal of any exposed β-glucan polysaccharides by the secreted glucanase Eng1. 28154008 2 20 theme polysaccharides 429:443 arg1 removal 397:403 enzymatic removal 387:403 enzymatic removal of any exposed β-glucan polysaccharides 387:443 The fungal pathogen Histoplasma capsulatum minimizes detection of β-glucan by host cells through at least two mechanisms: concealment of β-glucans beneath α-glucans and enzymatic removal of any exposed β-glucan polysaccharides by the secreted glucanase Eng1. 28154008 8 21 theme receptor 1361:1368 arg1 Dectin-1 1370:1377 the host β-glucan receptor Dectin-1 1343:1377 the host β-glucan receptor Dectin-1 1343:1377 Exg8 has a higher specific activity than Eng1 for β1,3-glucans; yet despite this, Exg8 does not reduce detection of yeasts by the host β-glucan receptor Dectin-1. 28154008 4 22 theme enzymatic 662:670 arg1 specificity 672:682 the enzymatic specificity 658:682 the enzymatic specificity of the Eng1 and Exg8 proteins 658:712 Here, we characterize the enzymatic specificity of the Eng1 and Exg8 proteins and show that Exg8 is an exo-β1,3-glucanase and Eng1 is an endo-β1,3-glucanase. 28154008 7 23 theme cells 1164:1168 arg1 infection 1146:1154 infection 1146:1154 infection of host cells 1146:1168 Both glucanases have near maximal activity at temperature and pH conditions experienced during infection of host cells, supporting roles in Histoplasma pathogenesis. 28154008 5 24 theme yeasts 897:902 arg1 activity 873:880 the total secreted glucanase activity 844:880 the total secreted glucanase activity of Histoplasma yeasts 844:902 Together, Eng1 and Exg8 account for nearly all of the total secreted glucanase activity of Histoplasma yeasts. 28154008 8 25 theme β-glucan 1352:1359 arg1 Dectin-1 1370:1377 the host β-glucan receptor Dectin-1 1343:1377 the host β-glucan receptor Dectin-1 1343:1377 Exg8 has a higher specific activity than Eng1 for β1,3-glucans; yet despite this, Exg8 does not reduce detection of yeasts by the host β-glucan receptor Dectin-1. 28154008 10 26 theme Histoplasma 1476:1486 arg1 yeasts 1488:1493 Histoplasma yeasts 1476:1493 Histoplasma yeasts 1476:1493 These results show that Histoplasma yeasts secrete two β1,3-glucanases and that Eng1 endoglucanase activity is the predominant factor responsible for removal of exposed cell wall β-glucans to minimize host detection of Histoplasma yeasts. 28154008 2 27 theme β-glucan 284:291 arg1 detection 271:279 detection 271:279 detection of β-glucan by host cells 271:305 The fungal pathogen Histoplasma capsulatum minimizes detection of β-glucan by host cells through at least two mechanisms: concealment of β-glucans beneath α-glucans and enzymatic removal of any exposed β-glucan polysaccharides by the secreted glucanase Eng1. 28154008 7 28 contain have 1067:1070 arg1 glucanases 1056:1065 Both glucanases 1051:1065 Both glucanases 1051:1065 Both glucanases have near maximal activity at temperature and pH conditions experienced during infection of host cells, supporting roles in Histoplasma pathogenesis. 28154008 7 28 contain have 1067:1070 arg2 activity 1085:1092 near maximal activity 1072:1092 near maximal activity 1072:1092 Both glucanases have near maximal activity at temperature and pH conditions experienced during infection of host cells, supporting roles in Histoplasma pathogenesis. 28154008 5 29 theme total 848:852 arg1 activity 873:880 the total secreted glucanase activity 844:880 the total secreted glucanase activity of Histoplasma yeasts 844:902 Together, Eng1 and Exg8 account for nearly all of the total secreted glucanase activity of Histoplasma yeasts. 28154008 7 30 theme Histoplasma 1191:1201 arg1 pathogenesis 1203:1214 Histoplasma pathogenesis 1191:1214 Histoplasma pathogenesis 1191:1214 Both glucanases have near maximal activity at temperature and pH conditions experienced during infection of host cells, supporting roles in Histoplasma pathogenesis. 28154008 10 31 theme endoglucanase 1537:1549 arg1 factor 1579:1584 the predominant factor 1563:1584 the predominant factor responsible for removal of exposed cell wall β-glucans to minimize host detection of Histoplasma yeasts 1563:1688 These results show that Histoplasma yeasts secrete two β1,3-glucanases and that Eng1 endoglucanase activity is the predominant factor responsible for removal of exposed cell wall β-glucans to minimize host detection of Histoplasma yeasts. 28154008 10 31 theme endoglucanase 1537:1549 arg1 activity 1551:1558 Eng1 endoglucanase activity 1532:1558 Eng1 endoglucanase activity 1532:1558 These results show that Histoplasma yeasts secrete two β1,3-glucanases and that Eng1 endoglucanase activity is the predominant factor responsible for removal of exposed cell wall β-glucans to minimize host detection of Histoplasma yeasts. 28154008 7 32 theme temperature 1097:1107 arg1 conditions 1116:1125 temperature and pH conditions 1097:1125 conditions 1116:1125 Both glucanases have near maximal activity at temperature and pH conditions experienced during infection of host cells, supporting roles in Histoplasma pathogenesis. 28154008 5 33 theme secreted 854:861 arg1 activity 873:880 the total secreted glucanase activity 844:880 the total secreted glucanase activity of Histoplasma yeasts 844:902 Together, Eng1 and Exg8 account for nearly all of the total secreted glucanase activity of Histoplasma yeasts. 28154008 2 34 theme glucanase 461:469 arg1 Eng1 471:474 the secreted glucanase Eng1 448:474 the secreted glucanase Eng1 448:474 The fungal pathogen Histoplasma capsulatum minimizes detection of β-glucan by host cells through at least two mechanisms: concealment of β-glucans beneath α-glucans and enzymatic removal of any exposed β-glucan polysaccharides by the secreted glucanase Eng1. 28154008 6 35 theme secretion 969:977 arg1 signal 979:984 a conventional secretion signal 954:984 a conventional secretion signal 954:984 Both Eng1 and Exg8 proteins are secreted through a conventional secretion signal and are modified post-translationally by O-linked glycosylation. 28154008 8 36 theme specific 1235:1242 arg1 activity 1244:1251 a higher specific activity 1226:1251 a higher specific activity than Eng1 for β1,3-glucans 1226:1278 Exg8 has a higher specific activity than Eng1 for β1,3-glucans; yet despite this, Exg8 does not reduce detection of yeasts by the host β-glucan receptor Dectin-1. 28154008 2 37 dep mechanisms 328:337 arg1 concealment 340:350 concealment 340:350 concealment of β-glucans beneath α-glucans 340:381 The fungal pathogen Histoplasma capsulatum minimizes detection of β-glucan by host cells through at least two mechanisms: concealment of β-glucans beneath α-glucans and enzymatic removal of any exposed β-glucan polysaccharides by the secreted glucanase Eng1. 28154008 2 37 dep mechanisms 328:337 arg1 mechanisms 328:337 at least two mechanisms 315:337 at least two mechanisms: concealment of β-glucans beneath α-glucans and enzymatic removal of any exposed β-glucan polysaccharides 315:443 The fungal pathogen Histoplasma capsulatum minimizes detection of β-glucan by host cells through at least two mechanisms: concealment of β-glucans beneath α-glucans and enzymatic removal of any exposed β-glucan polysaccharides by the secreted glucanase Eng1. 28154008 2 37 dep mechanisms 328:337 arg1 removal 397:403 enzymatic removal 387:403 enzymatic removal of any exposed β-glucan polysaccharides 387:443 The fungal pathogen Histoplasma capsulatum minimizes detection of β-glucan by host cells through at least two mechanisms: concealment of β-glucans beneath α-glucans and enzymatic removal of any exposed β-glucan polysaccharides by the secreted glucanase Eng1. 28154008 2 38 theme enzymatic 387:395 arg1 mechanisms 328:337 at least two mechanisms 315:337 at least two mechanisms: concealment of β-glucans beneath α-glucans and enzymatic removal of any exposed β-glucan polysaccharides 315:443 The fungal pathogen Histoplasma capsulatum minimizes detection of β-glucan by host cells through at least two mechanisms: concealment of β-glucans beneath α-glucans and enzymatic removal of any exposed β-glucan polysaccharides by the secreted glucanase Eng1. 28154008 2 38 theme enzymatic 387:395 arg1 removal 397:403 enzymatic removal 387:403 enzymatic removal of any exposed β-glucan polysaccharides 387:443 The fungal pathogen Histoplasma capsulatum minimizes detection of β-glucan by host cells through at least two mechanisms: concealment of β-glucans beneath α-glucans and enzymatic removal of any exposed β-glucan polysaccharides by the secreted glucanase Eng1. 28154008 2 39 theme secreted 452:459 arg1 Eng1 471:474 the secreted glucanase Eng1 448:474 the secreted glucanase Eng1 448:474 The fungal pathogen Histoplasma capsulatum minimizes detection of β-glucan by host cells through at least two mechanisms: concealment of β-glucans beneath α-glucans and enzymatic removal of any exposed β-glucan polysaccharides by the secreted glucanase Eng1. 28154008 6 40 theme conventional 956:967 arg1 signal 979:984 a conventional secretion signal 954:984 a conventional secretion signal 954:984 Both Eng1 and Exg8 proteins are secreted through a conventional secretion signal and are modified post-translationally by O-linked glycosylation. 28154008 8 41 theme yeasts 1333:1338 arg1 detection 1320:1328 detection 1320:1328 detection of yeasts by the host β-glucan receptor Dectin-1 1320:1377 Exg8 has a higher specific activity than Eng1 for β1,3-glucans; yet despite this, Exg8 does not reduce detection of yeasts by the host β-glucan receptor Dectin-1. 28154008 1 42 theme host 199:202 arg1 cells 211:215 host immune cells 199:215 host immune cells 199:215 Fungal cell walls contain β-glucan polysaccharides that stimulate immune responses when recognized by host immune cells. 28154008 1 43 theme Fungal 97:102 arg1 walls 109:113 Fungal cell walls 97:113 Fungal cell walls 97:113 Fungal cell walls contain β-glucan polysaccharides that stimulate immune responses when recognized by host immune cells. 28154008 1 44 theme immune 204:209 arg1 cells 211:215 host immune cells 199:215 host immune cells 199:215 Fungal cell walls contain β-glucan polysaccharides that stimulate immune responses when recognized by host immune cells. 28154008 0 45 theme Major 22:26 arg1 Exg8 9:12 Exg8 9:12 Exg8 9:12 Eng1 and Exg8 Are the Major β-Glucanases Secreted by the Fungal Pathogen Histoplasma capsulatum. 28154008 0 45 theme Major 22:26 arg1 Eng1 0:3 Eng1 0:3 Eng1 0:3 Eng1 and Exg8 Are the Major β-Glucanases Secreted by the Fungal Pathogen Histoplasma capsulatum. 28154008 0 45 theme Major 22:26 arg1 β-Glucanases 28:39 the Major β-Glucanases 18:39 the Major β-Glucanases Secreted by the Fungal Pathogen Histoplasma capsulatum 18:94 Eng1 and Exg8 Are the Major β-Glucanases Secreted by the Fungal Pathogen Histoplasma capsulatum. 28154008 4 46 theme proteins 705:712 arg1 specificity 672:682 the enzymatic specificity 658:682 the enzymatic specificity of the Eng1 and Exg8 proteins 658:712 Here, we characterize the enzymatic specificity of the Eng1 and Exg8 proteins and show that Exg8 is an exo-β1,3-glucanase and Eng1 is an endo-β1,3-glucanase. 28154008 7 47 theme near 1072:1075 arg1 activity 1085:1092 near maximal activity 1072:1092 near maximal activity 1072:1092 Both glucanases have near maximal activity at temperature and pH conditions experienced during infection of host cells, supporting roles in Histoplasma pathogenesis. 28154008 5 48 theme glucanase 863:871 arg1 activity 873:880 the total secreted glucanase activity 844:880 the total secreted glucanase activity of Histoplasma yeasts 844:902 Together, Eng1 and Exg8 account for nearly all of the total secreted glucanase activity of Histoplasma yeasts. 28154008 2 49 theme β-glucan 420:427 arg1 polysaccharides 429:443 any exposed β-glucan polysaccharides 408:443 any exposed β-glucan polysaccharides 408:443 The fungal pathogen Histoplasma capsulatum minimizes detection of β-glucan by host cells through at least two mechanisms: concealment of β-glucans beneath α-glucans and enzymatic removal of any exposed β-glucan polysaccharides by the secreted glucanase Eng1. 28154008 8 50 theme higher 1228:1233 arg1 activity 1244:1251 a higher specific activity 1226:1251 a higher specific activity than Eng1 for β1,3-glucans 1226:1278 Exg8 has a higher specific activity than Eng1 for β1,3-glucans; yet despite this, Exg8 does not reduce detection of yeasts by the host β-glucan receptor Dectin-1. 28154008 7 51 theme maximal 1077:1083 arg1 activity 1085:1092 near maximal activity 1072:1092 near maximal activity 1072:1092 Both glucanases have near maximal activity at temperature and pH conditions experienced during infection of host cells, supporting roles in Histoplasma pathogenesis. 28154008 2 52 theme exposed 412:418 arg1 polysaccharides 429:443 any exposed β-glucan polysaccharides 408:443 any exposed β-glucan polysaccharides 408:443 The fungal pathogen Histoplasma capsulatum minimizes detection of β-glucan by host cells through at least two mechanisms: concealment of β-glucans beneath α-glucans and enzymatic removal of any exposed β-glucan polysaccharides by the secreted glucanase Eng1. 28154008 7 53 theme host 1159:1162 arg1 cells 1164:1168 host cells 1159:1168 host cells 1159:1168 Both glucanases have near maximal activity at temperature and pH conditions experienced during infection of host cells, supporting roles in Histoplasma pathogenesis. 28154008 10 54 theme host 1653:1656 arg1 detection 1658:1666 host detection 1653:1666 host detection of Histoplasma yeasts 1653:1688 These results show that Histoplasma yeasts secrete two β1,3-glucanases and that Eng1 endoglucanase activity is the predominant factor responsible for removal of exposed cell wall β-glucans to minimize host detection of Histoplasma yeasts. 28154008 10 55 theme Eng1 1532:1535 arg1 factor 1579:1584 the predominant factor 1563:1584 the predominant factor responsible for removal of exposed cell wall β-glucans to minimize host detection of Histoplasma yeasts 1563:1688 These results show that Histoplasma yeasts secrete two β1,3-glucanases and that Eng1 endoglucanase activity is the predominant factor responsible for removal of exposed cell wall β-glucans to minimize host detection of Histoplasma yeasts. 28154008 10 55 theme Eng1 1532:1535 arg1 activity 1551:1558 Eng1 endoglucanase activity 1532:1558 Eng1 endoglucanase activity 1532:1558 These results show that Histoplasma yeasts secrete two β1,3-glucanases and that Eng1 endoglucanase activity is the predominant factor responsible for removal of exposed cell wall β-glucans to minimize host detection of Histoplasma yeasts. 28154008 2 56 theme fungal 222:227 arg1 pathogen 229:236 The fungal pathogen 218:236 The fungal pathogen Histoplasma capsulatum 218:259 The fungal pathogen Histoplasma capsulatum minimizes detection of β-glucan by host cells through at least two mechanisms: concealment of β-glucans beneath α-glucans and enzymatic removal of any exposed β-glucan polysaccharides by the secreted glucanase Eng1. 28154008 1 57 theme cell 104:107 arg1 walls 109:113 Fungal cell walls 97:113 Fungal cell walls 97:113 Fungal cell walls contain β-glucan polysaccharides that stimulate immune responses when recognized by host immune cells. 28154008 6 58 mod modified 994:1001 arg3 glycosylation 1036:1048 O-linked glycosylation 1027:1048 O-linked glycosylation 1027:1048 Both Eng1 and Exg8 proteins are secreted through a conventional secretion signal and are modified post-translationally by O-linked glycosylation. 28154008 6 58 mod modified 994:1001 arg1 Eng1 910:913 Eng1 910:913 Eng1 910:913 Both Eng1 and Exg8 proteins are secreted through a conventional secretion signal and are modified post-translationally by O-linked glycosylation. 28154008 3 59 theme glucanase 522:530 arg1 Exg8 532:535 the putative glucanase Exg8 509:535 the putative glucanase Exg8 509:535 Histoplasma yeasts also secrete the putative glucanase Exg8, which may serve a similar role as Eng1 in removing exposed β-glucans from the yeast cell surface. 28154008 10 60 theme exposed 1613:1619 arg1 β-glucans 1631:1639 exposed cell wall β-glucans 1613:1639 exposed cell wall β-glucans 1613:1639 These results show that Histoplasma yeasts secrete two β1,3-glucanases and that Eng1 endoglucanase activity is the predominant factor responsible for removal of exposed cell wall β-glucans to minimize host detection of Histoplasma yeasts. 28154008 6 61 theme Exg8 919:922 arg1 proteins 924:931 Exg8 proteins 919:931 Exg8 proteins 919:931 Both Eng1 and Exg8 proteins are secreted through a conventional secretion signal and are modified post-translationally by O-linked glycosylation. 28154008 8 62 contain has 1222:1224 arg2 activity 1244:1251 a higher specific activity 1226:1251 a higher specific activity than Eng1 for β1,3-glucans 1226:1278 Exg8 has a higher specific activity than Eng1 for β1,3-glucans; yet despite this, Exg8 does not reduce detection of yeasts by the host β-glucan receptor Dectin-1. 28154008 8 62 contain has 1222:1224 arg1 Exg8 1217:1220 Exg8 1217:1220 Exg8 1217:1220 Exg8 has a higher specific activity than Eng1 for β1,3-glucans; yet despite this, Exg8 does not reduce detection of yeasts by the host β-glucan receptor Dectin-1. 28154008 6 63 link O-linked 1027:1034 arg1 glycosylation 1036:1048 O-linked glycosylation 1027:1048 O-linked glycosylation 1027:1048 Both Eng1 and Exg8 proteins are secreted through a conventional secretion signal and are modified post-translationally by O-linked glycosylation. 28154008 8 64 theme host 1347:1350 arg1 Dectin-1 1370:1377 the host β-glucan receptor Dectin-1 1343:1377 the host β-glucan receptor Dectin-1 1343:1377 Exg8 has a higher specific activity than Eng1 for β1,3-glucans; yet despite this, Exg8 does not reduce detection of yeasts by the host β-glucan receptor Dectin-1. 28154008 10 65 theme yeasts 1683:1688 arg1 detection 1658:1666 host detection 1653:1666 host detection of Histoplasma yeasts 1653:1688 These results show that Histoplasma yeasts secrete two β1,3-glucanases and that Eng1 endoglucanase activity is the predominant factor responsible for removal of exposed cell wall β-glucans to minimize host detection of Histoplasma yeasts. 28154008 1 66 theme β-glucan 123:130 arg1 polysaccharides 132:146 β-glucan polysaccharides 123:146 β-glucan polysaccharides that stimulate immune responses when recognized by host immune cells 123:215 Fungal cell walls contain β-glucan polysaccharides that stimulate immune responses when recognized by host immune cells. 28154008 6 67 theme O-linked 1027:1034 arg1 glycosylation 1036:1048 O-linked glycosylation 1027:1048 O-linked glycosylation 1027:1048 Both Eng1 and Exg8 proteins are secreted through a conventional secretion signal and are modified post-translationally by O-linked glycosylation. 28154008 2 68 dep pathogen 229:236 arg1 capsulatum 250:259 Histoplasma capsulatum 238:259 The fungal pathogen Histoplasma capsulatum 218:259 The fungal pathogen Histoplasma capsulatum minimizes detection of β-glucan by host cells through at least two mechanisms: concealment of β-glucans beneath α-glucans and enzymatic removal of any exposed β-glucan polysaccharides by the secreted glucanase Eng1. 28154008 3 69 theme yeast 616:620 arg1 surface 627:633 the yeast cell surface 612:633 the yeast cell surface 612:633 Histoplasma yeasts also secrete the putative glucanase Exg8, which may serve a similar role as Eng1 in removing exposed β-glucans from the yeast cell surface. 28154008 4 70 theme Eng1 691:694 arg1 proteins 705:712 the Eng1 and Exg8 proteins 687:712 proteins 705:712 Here, we characterize the enzymatic specificity of the Eng1 and Exg8 proteins and show that Exg8 is an exo-β1,3-glucanase and Eng1 is an endo-β1,3-glucanase. 28154008 10 71 theme Histoplasma 1671:1681 arg1 yeasts 1683:1688 Histoplasma yeasts 1671:1688 Histoplasma yeasts 1671:1688 These results show that Histoplasma yeasts secrete two β1,3-glucanases and that Eng1 endoglucanase activity is the predominant factor responsible for removal of exposed cell wall β-glucans to minimize host detection of Histoplasma yeasts. 28154008 10 72 theme β-glucans 1631:1639 arg1 removal 1602:1608 removal 1602:1608 removal of exposed cell wall β-glucans to minimize host detection of Histoplasma yeasts 1602:1688 These results show that Histoplasma yeasts secrete two β1,3-glucanases and that Eng1 endoglucanase activity is the predominant factor responsible for removal of exposed cell wall β-glucans to minimize host detection of Histoplasma yeasts. 28154008 3 73 theme cell 622:625 arg1 surface 627:633 the yeast cell surface 612:633 the yeast cell surface 612:633 Histoplasma yeasts also secrete the putative glucanase Exg8, which may serve a similar role as Eng1 in removing exposed β-glucans from the yeast cell surface. 28154008 9 74 from contrast 1434:1441 arg1 dispensable 1396:1406 dispensable 1396:1406 dispensable 1396:1406 Exg8 is largely dispensable for virulence in vivo, in contrast to Eng1. 28154008 2 75 theme α-glucans 373:381 arg1 concealment 340:350 concealment 340:350 concealment of β-glucans beneath α-glucans 340:381 The fungal pathogen Histoplasma capsulatum minimizes detection of β-glucan by host cells through at least two mechanisms: concealment of β-glucans beneath α-glucans and enzymatic removal of any exposed β-glucan polysaccharides by the secreted glucanase Eng1. 28154008 2 75 theme α-glucans 373:381 arg1 mechanisms 328:337 at least two mechanisms 315:337 at least two mechanisms: concealment of β-glucans beneath α-glucans and enzymatic removal of any exposed β-glucan polysaccharides 315:443 The fungal pathogen Histoplasma capsulatum minimizes detection of β-glucan by host cells through at least two mechanisms: concealment of β-glucans beneath α-glucans and enzymatic removal of any exposed β-glucan polysaccharides by the secreted glucanase Eng1. 28154008 2 75 theme α-glucans 373:381 arg1 removal 397:403 enzymatic removal 387:403 enzymatic removal of any exposed β-glucan polysaccharides 387:443 The fungal pathogen Histoplasma capsulatum minimizes detection of β-glucan by host cells through at least two mechanisms: concealment of β-glucans beneath α-glucans and enzymatic removal of any exposed β-glucan polysaccharides by the secreted glucanase Eng1. 28154008 10 76 theme responsible 1586:1596 arg1 factor 1579:1584 the predominant factor 1563:1584 the predominant factor responsible for removal of exposed cell wall β-glucans to minimize host detection of Histoplasma yeasts 1563:1688 These results show that Histoplasma yeasts secrete two β1,3-glucanases and that Eng1 endoglucanase activity is the predominant factor responsible for removal of exposed cell wall β-glucans to minimize host detection of Histoplasma yeasts. 28154008 10 76 theme responsible 1586:1596 arg1 activity 1551:1558 Eng1 endoglucanase activity 1532:1558 Eng1 endoglucanase activity 1532:1558 These results show that Histoplasma yeasts secrete two β1,3-glucanases and that Eng1 endoglucanase activity is the predominant factor responsible for removal of exposed cell wall β-glucans to minimize host detection of Histoplasma yeasts. 27465797 1 0 theme kinase 382:387 arg1 activation 389:398 general control nonderepressible 2 (GCN2) kinase activation 340:398 general control nonderepressible 2 (GCN2) kinase activation 340:398 PURPOSE Considering the referred beneficial effects of protein restriction on diabetic nephropathy (DN) and the role of renal endothelium in its pathogenesis, we evaluated the effect of general control nonderepressible 2 (GCN2) kinase activation, a sensor of amino acid deprivation, on known detrimental molecular pathways in primary human glomerular endothelial cells (GEnC). 27465797 1 0 theme kinase 382:387 arg1 sensor 403:408 a sensor 401:408 a sensor of amino acid deprivation 401:434 PURPOSE Considering the referred beneficial effects of protein restriction on diabetic nephropathy (DN) and the role of renal endothelium in its pathogenesis, we evaluated the effect of general control nonderepressible 2 (GCN2) kinase activation, a sensor of amino acid deprivation, on known detrimental molecular pathways in primary human glomerular endothelial cells (GEnC). 27465797 2 1 theme high-glucose 574:585 arg1 conditions 587:596 normal or high-glucose conditions 564:596 normal or high-glucose conditions 564:596 METHODS GEnC were cultured under normal or high-glucose conditions in the presence or not of the GCN2 kinase activator, tryptophanol. 27465797 1 2 theme renal 274:278 arg1 endothelium 280:290 renal endothelium 274:290 renal endothelium 274:290 PURPOSE Considering the referred beneficial effects of protein restriction on diabetic nephropathy (DN) and the role of renal endothelium in its pathogenesis, we evaluated the effect of general control nonderepressible 2 (GCN2) kinase activation, a sensor of amino acid deprivation, on known detrimental molecular pathways in primary human glomerular endothelial cells (GEnC). 27465797 4 3 theme protein 867:873 arg1 PKC 885:887 PKC 885:887 PKC 885:887 Activities of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and protein kinase C (PKC) were assessed by commercial activity assays, sorbitol colorimetrically, methylglyoxal by ELISA and O-linked β-N-acetyl glucosamine (O-GlcNAc)-modified proteins by western blotting. 27465797 4 3 theme protein 867:873 arg1 C 882:882 protein kinase C 867:882 protein kinase C (PKC) 867:888 Activities of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and protein kinase C (PKC) were assessed by commercial activity assays, sorbitol colorimetrically, methylglyoxal by ELISA and O-linked β-N-acetyl glucosamine (O-GlcNAc)-modified proteins by western blotting. 27465797 6 4 theme O-GlcNAc-modified 1239:1255 arg1 proteins 1257:1264 the O-GlcNAc-modified proteins 1235:1264 the O-GlcNAc-modified proteins that produced by the hexosamine pathway 1235:1304 Also it increased the polyol pathway product sorbitol, PKC activity, the level of the O-GlcNAc-modified proteins that produced by the hexosamine pathway and the advanced glycation endproducts' precursor methylglyoxal. 27465797 1 5 theme known 440:444 arg1 pathways 468:475 known detrimental molecular pathways 440:475 known detrimental molecular pathways in primary human glomerular endothelial cells (GEnC) 440:528 PURPOSE Considering the referred beneficial effects of protein restriction on diabetic nephropathy (DN) and the role of renal endothelium in its pathogenesis, we evaluated the effect of general control nonderepressible 2 (GCN2) kinase activation, a sensor of amino acid deprivation, on known detrimental molecular pathways in primary human glomerular endothelial cells (GEnC). 27465797 4 6 theme 3-phosphate 829:839 arg1 dehydrogenase 841:853 glyceraldehyde 3-phosphate dehydrogenase 814:853 glyceraldehyde 3-phosphate dehydrogenase (GAPDH) 814:861 Activities of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and protein kinase C (PKC) were assessed by commercial activity assays, sorbitol colorimetrically, methylglyoxal by ELISA and O-linked β-N-acetyl glucosamine (O-GlcNAc)-modified proteins by western blotting. 27465797 4 6 theme 3-phosphate 829:839 arg1 GAPDH 856:860 GAPDH 856:860 GAPDH 856:860 Activities of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and protein kinase C (PKC) were assessed by commercial activity assays, sorbitol colorimetrically, methylglyoxal by ELISA and O-linked β-N-acetyl glucosamine (O-GlcNAc)-modified proteins by western blotting. 27465797 7 7 theme above 1423:1427 arg1 alterations 1450:1460 the above high-glucose-induced alterations 1419:1460 the above high-glucose-induced alterations 1419:1460 Co-treatment of GEnC with tryptophanol restored the above high-glucose-induced alterations. 27465797 1 8 theme molecular 458:466 arg1 pathways 468:475 known detrimental molecular pathways 440:475 known detrimental molecular pathways in primary human glomerular endothelial cells (GEnC) 440:528 PURPOSE Considering the referred beneficial effects of protein restriction on diabetic nephropathy (DN) and the role of renal endothelium in its pathogenesis, we evaluated the effect of general control nonderepressible 2 (GCN2) kinase activation, a sensor of amino acid deprivation, on known detrimental molecular pathways in primary human glomerular endothelial cells (GEnC). 27465797 1 9 theme protein 209:215 arg1 restriction 217:227 protein restriction 209:227 protein restriction 209:227 PURPOSE Considering the referred beneficial effects of protein restriction on diabetic nephropathy (DN) and the role of renal endothelium in its pathogenesis, we evaluated the effect of general control nonderepressible 2 (GCN2) kinase activation, a sensor of amino acid deprivation, on known detrimental molecular pathways in primary human glomerular endothelial cells (GEnC). 27465797 1 10 from role 266:269 arg1 nephropathy 241:251 diabetic nephropathy 232:251 diabetic nephropathy (DN) 232:256 PURPOSE Considering the referred beneficial effects of protein restriction on diabetic nephropathy (DN) and the role of renal endothelium in its pathogenesis, we evaluated the effect of general control nonderepressible 2 (GCN2) kinase activation, a sensor of amino acid deprivation, on known detrimental molecular pathways in primary human glomerular endothelial cells (GEnC). 27465797 1 10 from role 266:269 arg1 pathogenesis 299:310 its pathogenesis 295:310 its pathogenesis 295:310 PURPOSE Considering the referred beneficial effects of protein restriction on diabetic nephropathy (DN) and the role of renal endothelium in its pathogenesis, we evaluated the effect of general control nonderepressible 2 (GCN2) kinase activation, a sensor of amino acid deprivation, on known detrimental molecular pathways in primary human glomerular endothelial cells (GEnC). 27465797 3 11 theme western 722:728 arg1 blotting 730:737 western blotting 722:737 western blotting 722:737 Glucose transporter 1 (GLUT1) expression was assessed by western blotting and reactive oxygen species (ROS) using a fluorogenic probe. 27465797 6 12 theme advanced 1314:1321 arg1 endproducts 1333:1343 the advanced glycation endproducts 1310:1343 the advanced glycation endproducts' precursor methylglyoxal 1310:1368 Also it increased the polyol pathway product sorbitol, PKC activity, the level of the O-GlcNAc-modified proteins that produced by the hexosamine pathway and the advanced glycation endproducts' precursor methylglyoxal. 27465797 1 13 theme activation 389:398 arg1 effect 330:335 the effect 326:335 the effect of general control nonderepressible 2 (GCN2) kinase activation, a sensor of amino acid deprivation, on known detrimental molecular pathways in primary human glomerular endothelial cells (GEnC) 326:528 PURPOSE Considering the referred beneficial effects of protein restriction on diabetic nephropathy (DN) and the role of renal endothelium in its pathogenesis, we evaluated the effect of general control nonderepressible 2 (GCN2) kinase activation, a sensor of amino acid deprivation, on known detrimental molecular pathways in primary human glomerular endothelial cells (GEnC). 27465797 8 14 theme CONCLUSIONS 1463:1473 arg1 Activation 1475:1484 CONCLUSIONS Activation 1463:1484 CONCLUSIONS Activation of GCN2 kinase 1463:1499 CONCLUSIONS Activation of GCN2 kinase protects GEnC from high-glucose-induced harmful molecular pathways. 27465797 2 15 dep presence 605:612 arg1 the 601:603 the 601:603 the 601:603 METHODS GEnC were cultured under normal or high-glucose conditions in the presence or not of the GCN2 kinase activator, tryptophanol. 27465797 4 16 theme C 882:882 arg1 Activities 800:809 Activities 800:809 Activities of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and protein kinase C (PKC) 800:888 Activities of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and protein kinase C (PKC) were assessed by commercial activity assays, sorbitol colorimetrically, methylglyoxal by ELISA and O-linked β-N-acetyl glucosamine (O-GlcNAc)-modified proteins by western blotting. 27465797 6 17 theme PKC 1208:1210 arg1 activity 1212:1219 PKC activity 1208:1219 PKC activity 1208:1219 Also it increased the polyol pathway product sorbitol, PKC activity, the level of the O-GlcNAc-modified proteins that produced by the hexosamine pathway and the advanced glycation endproducts' precursor methylglyoxal. 27465797 3 18 theme oxygen 752:757 arg1 species 759:765 reactive oxygen species 743:765 reactive oxygen species (ROS) 743:771 Glucose transporter 1 (GLUT1) expression was assessed by western blotting and reactive oxygen species (ROS) using a fluorogenic probe. 27465797 3 18 theme oxygen 752:757 arg1 ROS 768:770 ROS 768:770 ROS 768:770 Glucose transporter 1 (GLUT1) expression was assessed by western blotting and reactive oxygen species (ROS) using a fluorogenic probe. 27465797 6 19 theme hexosamine 1287:1296 arg1 pathway 1298:1304 the hexosamine pathway 1283:1304 the hexosamine pathway 1283:1304 Also it increased the polyol pathway product sorbitol, PKC activity, the level of the O-GlcNAc-modified proteins that produced by the hexosamine pathway and the advanced glycation endproducts' precursor methylglyoxal. 27465797 4 20 dep ELISA 979:983 arg1 proteins 1041:1048 -modified proteins 1031:1048 -modified proteins 1031:1048 Activities of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and protein kinase C (PKC) were assessed by commercial activity assays, sorbitol colorimetrically, methylglyoxal by ELISA and O-linked β-N-acetyl glucosamine (O-GlcNAc)-modified proteins by western blotting. 27465797 2 21 theme normal 564:569 arg1 conditions 587:596 normal or high-glucose conditions 564:596 normal or high-glucose conditions 564:596 METHODS GEnC were cultured under normal or high-glucose conditions in the presence or not of the GCN2 kinase activator, tryptophanol. 27465797 8 22 theme kinase 1494:1499 arg1 Activation 1475:1484 CONCLUSIONS Activation 1463:1484 CONCLUSIONS Activation of GCN2 kinase 1463:1499 CONCLUSIONS Activation of GCN2 kinase protects GEnC from high-glucose-induced harmful molecular pathways. 27465797 1 23 theme acid 419:422 arg1 deprivation 424:434 amino acid deprivation 413:434 amino acid deprivation 413:434 PURPOSE Considering the referred beneficial effects of protein restriction on diabetic nephropathy (DN) and the role of renal endothelium in its pathogenesis, we evaluated the effect of general control nonderepressible 2 (GCN2) kinase activation, a sensor of amino acid deprivation, on known detrimental molecular pathways in primary human glomerular endothelial cells (GEnC). 27465797 6 24 theme pathway 1182:1188 arg1 sorbitol 1198:1205 the polyol pathway product sorbitol 1171:1205 the polyol pathway product sorbitol 1171:1205 Also it increased the polyol pathway product sorbitol, PKC activity, the level of the O-GlcNAc-modified proteins that produced by the hexosamine pathway and the advanced glycation endproducts' precursor methylglyoxal. 27465797 0 25 theme human 65:69 arg1 cells 94:98 human glomerular endothelial cells 65:98 human glomerular endothelial cells 65:98 Activation of general control nonderepressible 2 kinase protects human glomerular endothelial cells from harmful high-glucose-induced molecular pathways. 27465797 1 26 theme general 340:346 arg1 activation 389:398 general control nonderepressible 2 (GCN2) kinase activation 340:398 general control nonderepressible 2 (GCN2) kinase activation 340:398 PURPOSE Considering the referred beneficial effects of protein restriction on diabetic nephropathy (DN) and the role of renal endothelium in its pathogenesis, we evaluated the effect of general control nonderepressible 2 (GCN2) kinase activation, a sensor of amino acid deprivation, on known detrimental molecular pathways in primary human glomerular endothelial cells (GEnC). 27465797 1 26 theme general 340:346 arg1 sensor 403:408 a sensor 401:408 a sensor of amino acid deprivation 401:434 PURPOSE Considering the referred beneficial effects of protein restriction on diabetic nephropathy (DN) and the role of renal endothelium in its pathogenesis, we evaluated the effect of general control nonderepressible 2 (GCN2) kinase activation, a sensor of amino acid deprivation, on known detrimental molecular pathways in primary human glomerular endothelial cells (GEnC). 27465797 1 27 theme referred 178:185 arg1 effects 198:204 the referred beneficial effects 174:204 the referred beneficial effects of protein restriction on diabetic nephropathy (DN) 174:256 PURPOSE Considering the referred beneficial effects of protein restriction on diabetic nephropathy (DN) and the role of renal endothelium in its pathogenesis, we evaluated the effect of general control nonderepressible 2 (GCN2) kinase activation, a sensor of amino acid deprivation, on known detrimental molecular pathways in primary human glomerular endothelial cells (GEnC). 27465797 8 28 theme high-glucose-induced 1520:1539 arg1 pathways 1559:1566 high-glucose-induced harmful molecular pathways 1520:1566 high-glucose-induced harmful molecular pathways 1520:1566 CONCLUSIONS Activation of GCN2 kinase protects GEnC from high-glucose-induced harmful molecular pathways. 27465797 0 29 theme endothelial 82:92 arg1 cells 94:98 human glomerular endothelial cells 65:98 human glomerular endothelial cells 65:98 Activation of general control nonderepressible 2 kinase protects human glomerular endothelial cells from harmful high-glucose-induced molecular pathways. 27465797 1 30 theme nonderepressible 356:371 arg1 activation 389:398 general control nonderepressible 2 (GCN2) kinase activation 340:398 general control nonderepressible 2 (GCN2) kinase activation 340:398 PURPOSE Considering the referred beneficial effects of protein restriction on diabetic nephropathy (DN) and the role of renal endothelium in its pathogenesis, we evaluated the effect of general control nonderepressible 2 (GCN2) kinase activation, a sensor of amino acid deprivation, on known detrimental molecular pathways in primary human glomerular endothelial cells (GEnC). 27465797 1 30 theme nonderepressible 356:371 arg1 sensor 403:408 a sensor 401:408 a sensor of amino acid deprivation 401:434 PURPOSE Considering the referred beneficial effects of protein restriction on diabetic nephropathy (DN) and the role of renal endothelium in its pathogenesis, we evaluated the effect of general control nonderepressible 2 (GCN2) kinase activation, a sensor of amino acid deprivation, on known detrimental molecular pathways in primary human glomerular endothelial cells (GEnC). 27465797 4 31 theme activity 918:925 arg1 assays 927:932 commercial activity assays 907:932 commercial activity assays 907:932 Activities of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and protein kinase C (PKC) were assessed by commercial activity assays, sorbitol colorimetrically, methylglyoxal by ELISA and O-linked β-N-acetyl glucosamine (O-GlcNAc)-modified proteins by western blotting. 27465797 4 31 theme activity 918:925 arg1 sorbitol 935:942 sorbitol 935:942 sorbitol colorimetrically 935:959 Activities of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and protein kinase C (PKC) were assessed by commercial activity assays, sorbitol colorimetrically, methylglyoxal by ELISA and O-linked β-N-acetyl glucosamine (O-GlcNAc)-modified proteins by western blotting. 27465797 4 31 theme activity 918:925 arg1 methylglyoxal 962:974 methylglyoxal 962:974 methylglyoxal 962:974 Activities of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and protein kinase C (PKC) were assessed by commercial activity assays, sorbitol colorimetrically, methylglyoxal by ELISA and O-linked β-N-acetyl glucosamine (O-GlcNAc)-modified proteins by western blotting. 27465797 8 32 theme molecular 1549:1557 arg1 pathways 1559:1566 high-glucose-induced harmful molecular pathways 1520:1566 high-glucose-induced harmful molecular pathways 1520:1566 CONCLUSIONS Activation of GCN2 kinase protects GEnC from high-glucose-induced harmful molecular pathways. 27465797 2 33 theme activator 640:648 arg1 presence 605:612 presence 605:612 presence 605:612 METHODS GEnC were cultured under normal or high-glucose conditions in the presence or not of the GCN2 kinase activator, tryptophanol. 27465797 7 34 with Co-treatment 1371:1382 arg1 tryptophanol 1397:1408 tryptophanol 1397:1408 tryptophanol 1397:1408 Co-treatment of GEnC with tryptophanol restored the above high-glucose-induced alterations. 27465797 5 35 theme High 1079:1082 arg1 glucose 1084:1090 RESULTS High glucose 1071:1090 RESULTS High glucose 1071:1090 RESULTS High glucose induced GLUT1 expression, increased ROS and inhibited GAPDH. 27465797 4 36 link O-linked 989:996 arg1 glucosamine 1009:1019 O-linked β-N-acetyl glucosamine 989:1019 O-linked β-N-acetyl glucosamine (O-GlcNAc) 989:1030 Activities of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and protein kinase C (PKC) were assessed by commercial activity assays, sorbitol colorimetrically, methylglyoxal by ELISA and O-linked β-N-acetyl glucosamine (O-GlcNAc)-modified proteins by western blotting. 27465797 4 36 link O-linked 989:996 arg1 O-GlcNAc 1022:1029 O-GlcNAc 1022:1029 O-GlcNAc 1022:1029 Activities of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and protein kinase C (PKC) were assessed by commercial activity assays, sorbitol colorimetrically, methylglyoxal by ELISA and O-linked β-N-acetyl glucosamine (O-GlcNAc)-modified proteins by western blotting. 27465797 2 37 theme GCN2 628:631 arg1 activator 640:648 the GCN2 kinase activator 624:648 the GCN2 kinase activator 624:648 METHODS GEnC were cultured under normal or high-glucose conditions in the presence or not of the GCN2 kinase activator, tryptophanol. 27465797 2 37 theme GCN2 628:631 arg1 tryptophanol 651:662 tryptophanol 651:662 tryptophanol 651:662 METHODS GEnC were cultured under normal or high-glucose conditions in the presence or not of the GCN2 kinase activator, tryptophanol. 27465797 0 38 theme high-glucose-induced 113:132 arg1 pathways 144:151 harmful high-glucose-induced molecular pathways 105:151 harmful high-glucose-induced molecular pathways 105:151 Activation of general control nonderepressible 2 kinase protects human glomerular endothelial cells from harmful high-glucose-induced molecular pathways. 27465797 0 39 theme general 14:20 arg1 kinase 49:54 general control nonderepressible 2 kinase 14:54 general control nonderepressible 2 kinase 14:54 Activation of general control nonderepressible 2 kinase protects human glomerular endothelial cells from harmful high-glucose-induced molecular pathways. 27465797 9 40 theme GCN2 1639:1642 arg1 kinase 1644:1649 GCN2 kinase 1639:1649 GCN2 kinase 1639:1649 By inhibiting concurrently many pathways involved in DN pathogenesis, GCN2 kinase may serve as a pharmaceutical target for the treatment of DN. 27465797 9 40 theme GCN2 1639:1642 arg1 target 1681:1686 a pharmaceutical target 1664:1686 a pharmaceutical target for the treatment of DN 1664:1710 By inhibiting concurrently many pathways involved in DN pathogenesis, GCN2 kinase may serve as a pharmaceutical target for the treatment of DN. 27465797 0 41 theme nonderepressible 30:45 arg1 kinase 49:54 general control nonderepressible 2 kinase 14:54 general control nonderepressible 2 kinase 14:54 Activation of general control nonderepressible 2 kinase protects human glomerular endothelial cells from harmful high-glucose-induced molecular pathways. 27465797 4 42 theme O-linked 989:996 arg1 glucosamine 1009:1019 O-linked β-N-acetyl glucosamine 989:1019 O-linked β-N-acetyl glucosamine (O-GlcNAc) 989:1030 Activities of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and protein kinase C (PKC) were assessed by commercial activity assays, sorbitol colorimetrically, methylglyoxal by ELISA and O-linked β-N-acetyl glucosamine (O-GlcNAc)-modified proteins by western blotting. 27465797 4 42 theme O-linked 989:996 arg1 O-GlcNAc 1022:1029 O-GlcNAc 1022:1029 O-GlcNAc 1022:1029 Activities of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and protein kinase C (PKC) were assessed by commercial activity assays, sorbitol colorimetrically, methylglyoxal by ELISA and O-linked β-N-acetyl glucosamine (O-GlcNAc)-modified proteins by western blotting. 27465797 1 43 theme glomerular 494:503 arg1 GEnC 524:527 GEnC 524:527 GEnC 524:527 PURPOSE Considering the referred beneficial effects of protein restriction on diabetic nephropathy (DN) and the role of renal endothelium in its pathogenesis, we evaluated the effect of general control nonderepressible 2 (GCN2) kinase activation, a sensor of amino acid deprivation, on known detrimental molecular pathways in primary human glomerular endothelial cells (GEnC). 27465797 1 43 theme glomerular 494:503 arg1 cells 517:521 primary human glomerular endothelial cells 480:521 primary human glomerular endothelial cells (GEnC) 480:528 PURPOSE Considering the referred beneficial effects of protein restriction on diabetic nephropathy (DN) and the role of renal endothelium in its pathogenesis, we evaluated the effect of general control nonderepressible 2 (GCN2) kinase activation, a sensor of amino acid deprivation, on known detrimental molecular pathways in primary human glomerular endothelial cells (GEnC). 27465797 0 44 theme kinase 49:54 arg1 Activation 0:9 Activation 0:9 Activation of general control nonderepressible 2 kinase 0:54 Activation of general control nonderepressible 2 kinase protects human glomerular endothelial cells from harmful high-glucose-induced molecular pathways. 27465797 3 45 theme transporter 673:683 arg1 expression 695:704 Glucose transporter 1 (GLUT1) expression 665:704 Glucose transporter 1 (GLUT1) expression 665:704 Glucose transporter 1 (GLUT1) expression was assessed by western blotting and reactive oxygen species (ROS) using a fluorogenic probe. 27465797 9 46 theme pharmaceutical 1666:1679 arg1 kinase 1644:1649 GCN2 kinase 1639:1649 GCN2 kinase 1639:1649 By inhibiting concurrently many pathways involved in DN pathogenesis, GCN2 kinase may serve as a pharmaceutical target for the treatment of DN. 27465797 9 46 theme pharmaceutical 1666:1679 arg1 target 1681:1686 a pharmaceutical target 1664:1686 a pharmaceutical target for the treatment of DN 1664:1710 By inhibiting concurrently many pathways involved in DN pathogenesis, GCN2 kinase may serve as a pharmaceutical target for the treatment of DN. 27465797 1 47 from pathways 468:475 arg1 GEnC 524:527 GEnC 524:527 GEnC 524:527 PURPOSE Considering the referred beneficial effects of protein restriction on diabetic nephropathy (DN) and the role of renal endothelium in its pathogenesis, we evaluated the effect of general control nonderepressible 2 (GCN2) kinase activation, a sensor of amino acid deprivation, on known detrimental molecular pathways in primary human glomerular endothelial cells (GEnC). 27465797 1 47 from pathways 468:475 arg1 cells 517:521 primary human glomerular endothelial cells 480:521 primary human glomerular endothelial cells (GEnC) 480:528 PURPOSE Considering the referred beneficial effects of protein restriction on diabetic nephropathy (DN) and the role of renal endothelium in its pathogenesis, we evaluated the effect of general control nonderepressible 2 (GCN2) kinase activation, a sensor of amino acid deprivation, on known detrimental molecular pathways in primary human glomerular endothelial cells (GEnC). 27465797 4 48 theme -modified 1031:1039 arg1 proteins 1041:1048 -modified proteins 1031:1048 -modified proteins 1031:1048 Activities of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and protein kinase C (PKC) were assessed by commercial activity assays, sorbitol colorimetrically, methylglyoxal by ELISA and O-linked β-N-acetyl glucosamine (O-GlcNAc)-modified proteins by western blotting. 27465797 1 49 from effect 330:335 arg1 pathways 468:475 known detrimental molecular pathways 440:475 known detrimental molecular pathways in primary human glomerular endothelial cells (GEnC) 440:528 PURPOSE Considering the referred beneficial effects of protein restriction on diabetic nephropathy (DN) and the role of renal endothelium in its pathogenesis, we evaluated the effect of general control nonderepressible 2 (GCN2) kinase activation, a sensor of amino acid deprivation, on known detrimental molecular pathways in primary human glomerular endothelial cells (GEnC). 27465797 6 50 theme proteins 1257:1264 arg1 sorbitol 1198:1205 the polyol pathway product sorbitol 1171:1205 the polyol pathway product sorbitol 1171:1205 Also it increased the polyol pathway product sorbitol, PKC activity, the level of the O-GlcNAc-modified proteins that produced by the hexosamine pathway and the advanced glycation endproducts' precursor methylglyoxal. 27465797 6 50 theme proteins 1257:1264 arg1 activity 1212:1219 PKC activity 1208:1219 PKC activity 1208:1219 Also it increased the polyol pathway product sorbitol, PKC activity, the level of the O-GlcNAc-modified proteins that produced by the hexosamine pathway and the advanced glycation endproducts' precursor methylglyoxal. 27465797 6 50 theme proteins 1257:1264 arg1 level 1226:1230 the level 1222:1230 the level of the O-GlcNAc-modified proteins that produced by the hexosamine pathway 1222:1304 Also it increased the polyol pathway product sorbitol, PKC activity, the level of the O-GlcNAc-modified proteins that produced by the hexosamine pathway and the advanced glycation endproducts' precursor methylglyoxal. 27465797 6 50 theme proteins 1257:1264 arg1 methylglyoxal 1356:1368 the advanced glycation endproducts' precursor methylglyoxal 1310:1368 the advanced glycation endproducts' precursor methylglyoxal 1310:1368 Also it increased the polyol pathway product sorbitol, PKC activity, the level of the O-GlcNAc-modified proteins that produced by the hexosamine pathway and the advanced glycation endproducts' precursor methylglyoxal. 27465797 1 51 theme endothelium 280:290 arg1 role 266:269 the role 262:269 the role of renal endothelium in its pathogenesis 262:310 PURPOSE Considering the referred beneficial effects of protein restriction on diabetic nephropathy (DN) and the role of renal endothelium in its pathogenesis, we evaluated the effect of general control nonderepressible 2 (GCN2) kinase activation, a sensor of amino acid deprivation, on known detrimental molecular pathways in primary human glomerular endothelial cells (GEnC). 27465797 1 51 theme endothelium 280:290 arg1 effects 198:204 the referred beneficial effects 174:204 the referred beneficial effects of protein restriction on diabetic nephropathy (DN) 174:256 PURPOSE Considering the referred beneficial effects of protein restriction on diabetic nephropathy (DN) and the role of renal endothelium in its pathogenesis, we evaluated the effect of general control nonderepressible 2 (GCN2) kinase activation, a sensor of amino acid deprivation, on known detrimental molecular pathways in primary human glomerular endothelial cells (GEnC). 27465797 9 52 theme DN 1709:1710 arg1 treatment 1696:1704 the treatment 1692:1704 the treatment of DN 1692:1710 By inhibiting concurrently many pathways involved in DN pathogenesis, GCN2 kinase may serve as a pharmaceutical target for the treatment of DN. 27465797 1 53 theme detrimental 446:456 arg1 pathways 468:475 known detrimental molecular pathways 440:475 known detrimental molecular pathways in primary human glomerular endothelial cells (GEnC) 440:528 PURPOSE Considering the referred beneficial effects of protein restriction on diabetic nephropathy (DN) and the role of renal endothelium in its pathogenesis, we evaluated the effect of general control nonderepressible 2 (GCN2) kinase activation, a sensor of amino acid deprivation, on known detrimental molecular pathways in primary human glomerular endothelial cells (GEnC). 27465797 4 54 theme glyceraldehyde 814:827 arg1 dehydrogenase 841:853 glyceraldehyde 3-phosphate dehydrogenase 814:853 glyceraldehyde 3-phosphate dehydrogenase (GAPDH) 814:861 Activities of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and protein kinase C (PKC) were assessed by commercial activity assays, sorbitol colorimetrically, methylglyoxal by ELISA and O-linked β-N-acetyl glucosamine (O-GlcNAc)-modified proteins by western blotting. 27465797 4 54 theme glyceraldehyde 814:827 arg1 GAPDH 856:860 GAPDH 856:860 GAPDH 856:860 Activities of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and protein kinase C (PKC) were assessed by commercial activity assays, sorbitol colorimetrically, methylglyoxal by ELISA and O-linked β-N-acetyl glucosamine (O-GlcNAc)-modified proteins by western blotting. 27465797 7 55 theme high-glucose-induced 1429:1448 arg1 alterations 1450:1460 the above high-glucose-induced alterations 1419:1460 the above high-glucose-induced alterations 1419:1460 Co-treatment of GEnC with tryptophanol restored the above high-glucose-induced alterations. 27465797 1 56 theme restriction 217:227 arg1 role 266:269 the role 262:269 the role of renal endothelium in its pathogenesis 262:310 PURPOSE Considering the referred beneficial effects of protein restriction on diabetic nephropathy (DN) and the role of renal endothelium in its pathogenesis, we evaluated the effect of general control nonderepressible 2 (GCN2) kinase activation, a sensor of amino acid deprivation, on known detrimental molecular pathways in primary human glomerular endothelial cells (GEnC). 27465797 1 56 theme restriction 217:227 arg1 effects 198:204 the referred beneficial effects 174:204 the referred beneficial effects of protein restriction on diabetic nephropathy (DN) 174:256 PURPOSE Considering the referred beneficial effects of protein restriction on diabetic nephropathy (DN) and the role of renal endothelium in its pathogenesis, we evaluated the effect of general control nonderepressible 2 (GCN2) kinase activation, a sensor of amino acid deprivation, on known detrimental molecular pathways in primary human glomerular endothelial cells (GEnC). 27465797 4 57 theme dehydrogenase 841:853 arg1 Activities 800:809 Activities 800:809 Activities of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and protein kinase C (PKC) 800:888 Activities of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and protein kinase C (PKC) were assessed by commercial activity assays, sorbitol colorimetrically, methylglyoxal by ELISA and O-linked β-N-acetyl glucosamine (O-GlcNAc)-modified proteins by western blotting. 27465797 3 58 theme reactive 743:750 arg1 species 759:765 reactive oxygen species 743:765 reactive oxygen species (ROS) 743:771 Glucose transporter 1 (GLUT1) expression was assessed by western blotting and reactive oxygen species (ROS) using a fluorogenic probe. 27465797 3 58 theme reactive 743:750 arg1 ROS 768:770 ROS 768:770 ROS 768:770 Glucose transporter 1 (GLUT1) expression was assessed by western blotting and reactive oxygen species (ROS) using a fluorogenic probe. 27465797 6 59 theme glycation 1323:1331 arg1 endproducts 1333:1343 the advanced glycation endproducts 1310:1343 the advanced glycation endproducts' precursor methylglyoxal 1310:1368 Also it increased the polyol pathway product sorbitol, PKC activity, the level of the O-GlcNAc-modified proteins that produced by the hexosamine pathway and the advanced glycation endproducts' precursor methylglyoxal. 27465797 1 60 theme primary 480:486 arg1 GEnC 524:527 GEnC 524:527 GEnC 524:527 PURPOSE Considering the referred beneficial effects of protein restriction on diabetic nephropathy (DN) and the role of renal endothelium in its pathogenesis, we evaluated the effect of general control nonderepressible 2 (GCN2) kinase activation, a sensor of amino acid deprivation, on known detrimental molecular pathways in primary human glomerular endothelial cells (GEnC). 27465797 1 60 theme primary 480:486 arg1 cells 517:521 primary human glomerular endothelial cells 480:521 primary human glomerular endothelial cells (GEnC) 480:528 PURPOSE Considering the referred beneficial effects of protein restriction on diabetic nephropathy (DN) and the role of renal endothelium in its pathogenesis, we evaluated the effect of general control nonderepressible 2 (GCN2) kinase activation, a sensor of amino acid deprivation, on known detrimental molecular pathways in primary human glomerular endothelial cells (GEnC). 27465797 1 61 theme diabetic 232:239 arg1 nephropathy 241:251 diabetic nephropathy 232:251 diabetic nephropathy (DN) 232:256 PURPOSE Considering the referred beneficial effects of protein restriction on diabetic nephropathy (DN) and the role of renal endothelium in its pathogenesis, we evaluated the effect of general control nonderepressible 2 (GCN2) kinase activation, a sensor of amino acid deprivation, on known detrimental molecular pathways in primary human glomerular endothelial cells (GEnC). 27465797 8 62 theme GCN2 1489:1492 arg1 kinase 1494:1499 GCN2 kinase 1489:1499 GCN2 kinase 1489:1499 CONCLUSIONS Activation of GCN2 kinase protects GEnC from high-glucose-induced harmful molecular pathways. 27465797 7 63 theme GEnC 1387:1390 arg1 Co-treatment 1371:1382 Co-treatment 1371:1382 Co-treatment of GEnC with tryptophanol 1371:1408 Co-treatment of GEnC with tryptophanol restored the above high-glucose-induced alterations. 27465797 5 64 theme RESULTS 1071:1077 arg1 glucose 1084:1090 RESULTS High glucose 1071:1090 RESULTS High glucose 1071:1090 RESULTS High glucose induced GLUT1 expression, increased ROS and inhibited GAPDH. 27465797 4 65 theme kinase 875:880 arg1 PKC 885:887 PKC 885:887 PKC 885:887 Activities of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and protein kinase C (PKC) were assessed by commercial activity assays, sorbitol colorimetrically, methylglyoxal by ELISA and O-linked β-N-acetyl glucosamine (O-GlcNAc)-modified proteins by western blotting. 27465797 4 65 theme kinase 875:880 arg1 C 882:882 protein kinase C 867:882 protein kinase C (PKC) 867:888 Activities of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and protein kinase C (PKC) were assessed by commercial activity assays, sorbitol colorimetrically, methylglyoxal by ELISA and O-linked β-N-acetyl glucosamine (O-GlcNAc)-modified proteins by western blotting. 27465797 1 66 theme amino 413:417 arg1 deprivation 424:434 amino acid deprivation 413:434 amino acid deprivation 413:434 PURPOSE Considering the referred beneficial effects of protein restriction on diabetic nephropathy (DN) and the role of renal endothelium in its pathogenesis, we evaluated the effect of general control nonderepressible 2 (GCN2) kinase activation, a sensor of amino acid deprivation, on known detrimental molecular pathways in primary human glomerular endothelial cells (GEnC). 27465797 6 67 theme product 1190:1196 arg1 sorbitol 1198:1205 the polyol pathway product sorbitol 1171:1205 the polyol pathway product sorbitol 1171:1205 Also it increased the polyol pathway product sorbitol, PKC activity, the level of the O-GlcNAc-modified proteins that produced by the hexosamine pathway and the advanced glycation endproducts' precursor methylglyoxal. 27465797 3 68 theme fluorogenic 781:791 arg1 probe 793:797 a fluorogenic probe 779:797 a fluorogenic probe 779:797 Glucose transporter 1 (GLUT1) expression was assessed by western blotting and reactive oxygen species (ROS) using a fluorogenic probe. 27465797 0 69 theme glomerular 71:80 arg1 cells 94:98 human glomerular endothelial cells 65:98 human glomerular endothelial cells 65:98 Activation of general control nonderepressible 2 kinase protects human glomerular endothelial cells from harmful high-glucose-induced molecular pathways. 27465797 1 70 theme deprivation 424:434 arg1 activation 389:398 general control nonderepressible 2 (GCN2) kinase activation 340:398 general control nonderepressible 2 (GCN2) kinase activation 340:398 PURPOSE Considering the referred beneficial effects of protein restriction on diabetic nephropathy (DN) and the role of renal endothelium in its pathogenesis, we evaluated the effect of general control nonderepressible 2 (GCN2) kinase activation, a sensor of amino acid deprivation, on known detrimental molecular pathways in primary human glomerular endothelial cells (GEnC). 27465797 1 70 theme deprivation 424:434 arg1 sensor 403:408 a sensor 401:408 a sensor of amino acid deprivation 401:434 PURPOSE Considering the referred beneficial effects of protein restriction on diabetic nephropathy (DN) and the role of renal endothelium in its pathogenesis, we evaluated the effect of general control nonderepressible 2 (GCN2) kinase activation, a sensor of amino acid deprivation, on known detrimental molecular pathways in primary human glomerular endothelial cells (GEnC). 27465797 8 71 theme harmful 1541:1547 arg1 pathways 1559:1566 high-glucose-induced harmful molecular pathways 1520:1566 high-glucose-induced harmful molecular pathways 1520:1566 CONCLUSIONS Activation of GCN2 kinase protects GEnC from high-glucose-induced harmful molecular pathways. 27465797 6 72 theme polyol 1175:1180 arg1 pathway 1182:1188 the polyol pathway 1171:1188 the polyol pathway product sorbitol 1171:1205 Also it increased the polyol pathway product sorbitol, PKC activity, the level of the O-GlcNAc-modified proteins that produced by the hexosamine pathway and the advanced glycation endproducts' precursor methylglyoxal. 27465797 6 73 theme precursor 1346:1354 arg1 methylglyoxal 1356:1368 the advanced glycation endproducts' precursor methylglyoxal 1310:1368 the advanced glycation endproducts' precursor methylglyoxal 1310:1368 Also it increased the polyol pathway product sorbitol, PKC activity, the level of the O-GlcNAc-modified proteins that produced by the hexosamine pathway and the advanced glycation endproducts' precursor methylglyoxal. 27465797 1 74 theme control 348:354 arg1 activation 389:398 general control nonderepressible 2 (GCN2) kinase activation 340:398 general control nonderepressible 2 (GCN2) kinase activation 340:398 PURPOSE Considering the referred beneficial effects of protein restriction on diabetic nephropathy (DN) and the role of renal endothelium in its pathogenesis, we evaluated the effect of general control nonderepressible 2 (GCN2) kinase activation, a sensor of amino acid deprivation, on known detrimental molecular pathways in primary human glomerular endothelial cells (GEnC). 27465797 1 74 theme control 348:354 arg1 sensor 403:408 a sensor 401:408 a sensor of amino acid deprivation 401:434 PURPOSE Considering the referred beneficial effects of protein restriction on diabetic nephropathy (DN) and the role of renal endothelium in its pathogenesis, we evaluated the effect of general control nonderepressible 2 (GCN2) kinase activation, a sensor of amino acid deprivation, on known detrimental molecular pathways in primary human glomerular endothelial cells (GEnC). 27465797 1 75 theme beneficial 187:196 arg1 effects 198:204 the referred beneficial effects 174:204 the referred beneficial effects of protein restriction on diabetic nephropathy (DN) 174:256 PURPOSE Considering the referred beneficial effects of protein restriction on diabetic nephropathy (DN) and the role of renal endothelium in its pathogenesis, we evaluated the effect of general control nonderepressible 2 (GCN2) kinase activation, a sensor of amino acid deprivation, on known detrimental molecular pathways in primary human glomerular endothelial cells (GEnC). 27465797 0 76 theme harmful 105:111 arg1 pathways 144:151 harmful high-glucose-induced molecular pathways 105:151 harmful high-glucose-induced molecular pathways 105:151 Activation of general control nonderepressible 2 kinase protects human glomerular endothelial cells from harmful high-glucose-induced molecular pathways. 27465797 1 77 from effects 198:204 arg1 nephropathy 241:251 diabetic nephropathy 232:251 diabetic nephropathy (DN) 232:256 PURPOSE Considering the referred beneficial effects of protein restriction on diabetic nephropathy (DN) and the role of renal endothelium in its pathogenesis, we evaluated the effect of general control nonderepressible 2 (GCN2) kinase activation, a sensor of amino acid deprivation, on known detrimental molecular pathways in primary human glomerular endothelial cells (GEnC). 27465797 1 77 from effects 198:204 arg1 pathogenesis 299:310 its pathogenesis 295:310 its pathogenesis 295:310 PURPOSE Considering the referred beneficial effects of protein restriction on diabetic nephropathy (DN) and the role of renal endothelium in its pathogenesis, we evaluated the effect of general control nonderepressible 2 (GCN2) kinase activation, a sensor of amino acid deprivation, on known detrimental molecular pathways in primary human glomerular endothelial cells (GEnC). 27465797 9 78 theme many 1596:1599 arg1 pathways 1601:1608 concurrently many pathways 1583:1608 concurrently many pathways involved in DN pathogenesis 1583:1636 By inhibiting concurrently many pathways involved in DN pathogenesis, GCN2 kinase may serve as a pharmaceutical target for the treatment of DN. 27465797 4 79 theme commercial 907:916 arg1 assays 927:932 commercial activity assays 907:932 commercial activity assays 907:932 Activities of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and protein kinase C (PKC) were assessed by commercial activity assays, sorbitol colorimetrically, methylglyoxal by ELISA and O-linked β-N-acetyl glucosamine (O-GlcNAc)-modified proteins by western blotting. 27465797 4 79 theme commercial 907:916 arg1 sorbitol 935:942 sorbitol 935:942 sorbitol colorimetrically 935:959 Activities of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and protein kinase C (PKC) were assessed by commercial activity assays, sorbitol colorimetrically, methylglyoxal by ELISA and O-linked β-N-acetyl glucosamine (O-GlcNAc)-modified proteins by western blotting. 27465797 4 79 theme commercial 907:916 arg1 methylglyoxal 962:974 methylglyoxal 962:974 methylglyoxal 962:974 Activities of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and protein kinase C (PKC) were assessed by commercial activity assays, sorbitol colorimetrically, methylglyoxal by ELISA and O-linked β-N-acetyl glucosamine (O-GlcNAc)-modified proteins by western blotting. 27465797 2 80 theme kinase 633:638 arg1 activator 640:648 the GCN2 kinase activator 624:648 the GCN2 kinase activator 624:648 METHODS GEnC were cultured under normal or high-glucose conditions in the presence or not of the GCN2 kinase activator, tryptophanol. 27465797 2 80 theme kinase 633:638 arg1 tryptophanol 651:662 tryptophanol 651:662 tryptophanol 651:662 METHODS GEnC were cultured under normal or high-glucose conditions in the presence or not of the GCN2 kinase activator, tryptophanol. 27465797 0 81 theme molecular 134:142 arg1 pathways 144:151 harmful high-glucose-induced molecular pathways 105:151 harmful high-glucose-induced molecular pathways 105:151 Activation of general control nonderepressible 2 kinase protects human glomerular endothelial cells from harmful high-glucose-induced molecular pathways. 27465797 1 82 theme GCN2 376:379 arg1 activation 389:398 general control nonderepressible 2 (GCN2) kinase activation 340:398 general control nonderepressible 2 (GCN2) kinase activation 340:398 PURPOSE Considering the referred beneficial effects of protein restriction on diabetic nephropathy (DN) and the role of renal endothelium in its pathogenesis, we evaluated the effect of general control nonderepressible 2 (GCN2) kinase activation, a sensor of amino acid deprivation, on known detrimental molecular pathways in primary human glomerular endothelial cells (GEnC). 27465797 1 82 theme GCN2 376:379 arg1 sensor 403:408 a sensor 401:408 a sensor of amino acid deprivation 401:434 PURPOSE Considering the referred beneficial effects of protein restriction on diabetic nephropathy (DN) and the role of renal endothelium in its pathogenesis, we evaluated the effect of general control nonderepressible 2 (GCN2) kinase activation, a sensor of amino acid deprivation, on known detrimental molecular pathways in primary human glomerular endothelial cells (GEnC). 27465797 5 83 theme GLUT1 1100:1104 arg1 expression 1106:1115 GLUT1 expression 1100:1115 GLUT1 expression 1100:1115 RESULTS High glucose induced GLUT1 expression, increased ROS and inhibited GAPDH. 27465797 9 84 theme DN 1622:1623 arg1 pathogenesis 1625:1636 DN pathogenesis 1622:1636 DN pathogenesis 1622:1636 By inhibiting concurrently many pathways involved in DN pathogenesis, GCN2 kinase may serve as a pharmaceutical target for the treatment of DN. 27465797 4 85 theme β-N-acetyl 998:1007 arg1 glucosamine 1009:1019 O-linked β-N-acetyl glucosamine 989:1019 O-linked β-N-acetyl glucosamine (O-GlcNAc) 989:1030 Activities of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and protein kinase C (PKC) were assessed by commercial activity assays, sorbitol colorimetrically, methylglyoxal by ELISA and O-linked β-N-acetyl glucosamine (O-GlcNAc)-modified proteins by western blotting. 27465797 4 85 theme β-N-acetyl 998:1007 arg1 O-GlcNAc 1022:1029 O-GlcNAc 1022:1029 O-GlcNAc 1022:1029 Activities of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and protein kinase C (PKC) were assessed by commercial activity assays, sorbitol colorimetrically, methylglyoxal by ELISA and O-linked β-N-acetyl glucosamine (O-GlcNAc)-modified proteins by western blotting. 27465797 0 86 theme control 22:28 arg1 kinase 49:54 general control nonderepressible 2 kinase 14:54 general control nonderepressible 2 kinase 14:54 Activation of general control nonderepressible 2 kinase protects human glomerular endothelial cells from harmful high-glucose-induced molecular pathways. 27465797 1 87 theme human 488:492 arg1 GEnC 524:527 GEnC 524:527 GEnC 524:527 PURPOSE Considering the referred beneficial effects of protein restriction on diabetic nephropathy (DN) and the role of renal endothelium in its pathogenesis, we evaluated the effect of general control nonderepressible 2 (GCN2) kinase activation, a sensor of amino acid deprivation, on known detrimental molecular pathways in primary human glomerular endothelial cells (GEnC). 27465797 1 87 theme human 488:492 arg1 cells 517:521 primary human glomerular endothelial cells 480:521 primary human glomerular endothelial cells (GEnC) 480:528 PURPOSE Considering the referred beneficial effects of protein restriction on diabetic nephropathy (DN) and the role of renal endothelium in its pathogenesis, we evaluated the effect of general control nonderepressible 2 (GCN2) kinase activation, a sensor of amino acid deprivation, on known detrimental molecular pathways in primary human glomerular endothelial cells (GEnC). 27465797 3 88 theme Glucose 665:671 arg1 GLUT1 688:692 GLUT1 688:692 GLUT1 688:692 Glucose transporter 1 (GLUT1) expression was assessed by western blotting and reactive oxygen species (ROS) using a fluorogenic probe. 27465797 3 88 theme Glucose 665:671 arg1 transporter 673:683 Glucose transporter 1 665:685 Glucose transporter 1 (GLUT1) expression 665:704 Glucose transporter 1 (GLUT1) expression was assessed by western blotting and reactive oxygen species (ROS) using a fluorogenic probe. 27465797 1 89 theme endothelial 505:515 arg1 GEnC 524:527 GEnC 524:527 GEnC 524:527 PURPOSE Considering the referred beneficial effects of protein restriction on diabetic nephropathy (DN) and the role of renal endothelium in its pathogenesis, we evaluated the effect of general control nonderepressible 2 (GCN2) kinase activation, a sensor of amino acid deprivation, on known detrimental molecular pathways in primary human glomerular endothelial cells (GEnC). 27465797 1 89 theme endothelial 505:515 arg1 cells 517:521 primary human glomerular endothelial cells 480:521 primary human glomerular endothelial cells (GEnC) 480:528 PURPOSE Considering the referred beneficial effects of protein restriction on diabetic nephropathy (DN) and the role of renal endothelium in its pathogenesis, we evaluated the effect of general control nonderepressible 2 (GCN2) kinase activation, a sensor of amino acid deprivation, on known detrimental molecular pathways in primary human glomerular endothelial cells (GEnC). 27465797 4 90 theme western 1053:1059 arg1 blotting 1061:1068 western blotting 1053:1068 western blotting 1053:1068 Activities of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and protein kinase C (PKC) were assessed by commercial activity assays, sorbitol colorimetrically, methylglyoxal by ELISA and O-linked β-N-acetyl glucosamine (O-GlcNAc)-modified proteins by western blotting. 27465797 1 91 dep nephropathy 241:251 arg1 DN 254:255 DN 254:255 DN 254:255 PURPOSE Considering the referred beneficial effects of protein restriction on diabetic nephropathy (DN) and the role of renal endothelium in its pathogenesis, we evaluated the effect of general control nonderepressible 2 (GCN2) kinase activation, a sensor of amino acid deprivation, on known detrimental molecular pathways in primary human glomerular endothelial cells (GEnC). 27345396 10 0 theme central 1197:1203 arg1 component 1205:1213 a central component 1195:1213 a central component linking metabolism to invasion and metastasis via an SIRT1/ERK/FOXM1 axis 1195:1287 Thus, O-GlcNAcylation is a central component linking metabolism to invasion and metastasis via an SIRT1/ERK/FOXM1 axis. 27345396 10 0 theme central 1197:1203 arg1 O-GlcNAcylation 1176:1190 O-GlcNAcylation 1176:1190 O-GlcNAcylation 1176:1190 Thus, O-GlcNAcylation is a central component linking metabolism to invasion and metastasis via an SIRT1/ERK/FOXM1 axis. 27345396 7 1 theme SIRT1-mediated 790:803 arg1 degradation 817:827 SIRT1-mediated proteasomal degradation 790:827 SIRT1-mediated proteasomal degradation of oncogenic transcription factor FOXM1 790:867 Reduced O-GlcNAcylation in cancer cells leads to SIRT1-mediated proteasomal degradation of oncogenic transcription factor FOXM1 in an MEK/ERK-dependent manner. 27345396 0 2 theme pathway 81:87 arg1 modulation 61:70 SIRT1 modulation 55:70 SIRT1 modulation of FOXM1 pathway 55:87 O-GlcNAcylation regulates breast cancer metastasis via SIRT1 modulation of FOXM1 pathway. 27345396 4 3 theme O-GlcNAcylation 448:462 arg1 suppression 433:443 suppression 433:443 suppression of O-GlcNAcylation 433:462 Cancers display elevated O-GlcNAcylation and suppression of O-GlcNAcylation inhibits cancer invasion and metastasis. 27345396 8 4 theme ubiquitination 956:969 arg1 regulation 936:945 OGT-mediated regulation 923:945 OGT-mediated regulation of FOXM1 ubiquitination 923:969 SIRT1 is critical for OGT-mediated regulation of FOXM1 ubiquitination and reducing SIRT1 activity reverses OGT-mediated regulation of FOXM1. 27345396 7 5 theme proteasomal 805:815 arg1 degradation 817:827 SIRT1-mediated proteasomal degradation 790:827 SIRT1-mediated proteasomal degradation of oncogenic transcription factor FOXM1 790:867 Reduced O-GlcNAcylation in cancer cells leads to SIRT1-mediated proteasomal degradation of oncogenic transcription factor FOXM1 in an MEK/ERK-dependent manner. 27345396 7 6 from O-GlcNAcylation 749:763 arg1 cells 775:779 cancer cells 768:779 cancer cells 768:779 Reduced O-GlcNAcylation in cancer cells leads to SIRT1-mediated proteasomal degradation of oncogenic transcription factor FOXM1 in an MEK/ERK-dependent manner. 27345396 9 7 from regulation 1108:1117 arg1 cells 1163:1167 breast cancer cells 1149:1167 breast cancer cells 1149:1167 Moreover, we show that SIRT1 levels are required for OGT-mediated regulation of invasion and metastasis in breast cancer cells. 27345396 6 8 dep -dependent 722:731 arg1 kinase 713:718 AMP-activated protein kinase α 691:720 AMP-activated protein kinase α 691:720 Reducing O-GlcNAcylation elevates SIRT1 levels and activity in an AMPK (AMP-activated protein kinase α)-dependent manner. 27345396 9 9 theme invasion 1122:1129 arg1 regulation 1108:1117 OGT-mediated regulation 1095:1117 OGT-mediated regulation of invasion and metastasis in breast cancer cells 1095:1167 Moreover, we show that SIRT1 levels are required for OGT-mediated regulation of invasion and metastasis in breast cancer cells. 27345396 8 10 theme FOXM1 950:954 arg1 ubiquitination 956:969 FOXM1 ubiquitination 950:969 FOXM1 ubiquitination 950:969 SIRT1 is critical for OGT-mediated regulation of FOXM1 ubiquitination and reducing SIRT1 activity reverses OGT-mediated regulation of FOXM1. 27345396 8 11 theme FOXM1 1035:1039 arg1 regulation 1021:1030 OGT-mediated regulation 1008:1030 OGT-mediated regulation of FOXM1 1008:1039 SIRT1 is critical for OGT-mediated regulation of FOXM1 ubiquitination and reducing SIRT1 activity reverses OGT-mediated regulation of FOXM1. 27345396 4 12 theme cancer 473:478 arg1 invasion 480:487 cancer invasion 473:487 cancer invasion 473:487 Cancers display elevated O-GlcNAcylation and suppression of O-GlcNAcylation inhibits cancer invasion and metastasis. 27345396 5 13 theme cancer 542:547 arg1 invasion 549:556 cancer invasion 542:556 cancer invasion 542:556 Here, we show that the regulation of cancer invasion by OGT is dependent on the NAD+-dependent deacetylase SIRT1. 27345396 8 14 theme reducing 975:982 arg1 activity 990:997 reducing SIRT1 activity 975:997 reducing SIRT1 activity 975:997 SIRT1 is critical for OGT-mediated regulation of FOXM1 ubiquitination and reducing SIRT1 activity reverses OGT-mediated regulation of FOXM1. 27345396 3 15 theme nutrient 254:261 arg1 OGT 325:327 OGT 325:327 OGT 325:327 The nutrient sensor O-linked-β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) modifies intracellular proteins with N-acetylglucosamine. 27345396 3 15 theme nutrient 254:261 arg1 transferase 312:322 The nutrient sensor O-linked-β-N-acetylglucosamine (O-GlcNAc) transferase 250:322 The nutrient sensor O-linked-β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) 250:328 The nutrient sensor O-linked-β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) modifies intracellular proteins with N-acetylglucosamine. 27345396 5 16 theme invasion 549:556 arg1 regulation 528:537 the regulation 524:537 the regulation of cancer invasion by OGT 524:563 Here, we show that the regulation of cancer invasion by OGT is dependent on the NAD+-dependent deacetylase SIRT1. 27345396 5 16 theme invasion 549:556 arg1 dependent 568:576 dependent 568:576 dependent 568:576 Here, we show that the regulation of cancer invasion by OGT is dependent on the NAD+-dependent deacetylase SIRT1. 27345396 6 17 theme Reducing 619:626 arg1 O-GlcNAcylation 628:642 Reducing O-GlcNAcylation 619:642 Reducing O-GlcNAcylation 619:642 Reducing O-GlcNAcylation elevates SIRT1 levels and activity in an AMPK (AMP-activated protein kinase α)-dependent manner. 27345396 3 18 theme sensor 263:268 arg1 OGT 325:327 OGT 325:327 OGT 325:327 The nutrient sensor O-linked-β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) modifies intracellular proteins with N-acetylglucosamine. 27345396 3 18 theme sensor 263:268 arg1 transferase 312:322 The nutrient sensor O-linked-β-N-acetylglucosamine (O-GlcNAc) transferase 250:322 The nutrient sensor O-linked-β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) 250:328 The nutrient sensor O-linked-β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) modifies intracellular proteins with N-acetylglucosamine. 27345396 3 19 theme intracellular 339:351 arg1 proteins 353:360 intracellular proteins 339:360 intracellular proteins with N-acetylglucosamine 339:385 The nutrient sensor O-linked-β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) modifies intracellular proteins with N-acetylglucosamine. 27345396 4 20 theme elevated 404:411 arg1 O-GlcNAcylation 413:427 elevated O-GlcNAcylation 404:427 elevated O-GlcNAcylation 404:427 Cancers display elevated O-GlcNAcylation and suppression of O-GlcNAcylation inhibits cancer invasion and metastasis. 27345396 8 21 theme SIRT1 984:988 arg1 activity 990:997 reducing SIRT1 activity 975:997 reducing SIRT1 activity 975:997 SIRT1 is critical for OGT-mediated regulation of FOXM1 ubiquitination and reducing SIRT1 activity reverses OGT-mediated regulation of FOXM1. 27345396 8 22 theme OGT-mediated 1008:1019 arg1 regulation 1021:1030 OGT-mediated regulation 1008:1030 OGT-mediated regulation of FOXM1 1008:1039 SIRT1 is critical for OGT-mediated regulation of FOXM1 ubiquitination and reducing SIRT1 activity reverses OGT-mediated regulation of FOXM1. 27345396 0 23 theme cancer 33:38 arg1 metastasis 40:49 breast cancer metastasis 26:49 breast cancer metastasis 26:49 O-GlcNAcylation regulates breast cancer metastasis via SIRT1 modulation of FOXM1 pathway. 27345396 3 24 theme O-GlcNAc 302:309 arg1 OGT 325:327 OGT 325:327 OGT 325:327 The nutrient sensor O-linked-β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) modifies intracellular proteins with N-acetylglucosamine. 27345396 3 24 theme O-GlcNAc 302:309 arg1 transferase 312:322 The nutrient sensor O-linked-β-N-acetylglucosamine (O-GlcNAc) transferase 250:322 The nutrient sensor O-linked-β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) 250:328 The nutrient sensor O-linked-β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) modifies intracellular proteins with N-acetylglucosamine. 27345396 1 25 theme aerobic 105:111 arg1 glycolysis 113:122 aerobic glycolysis 105:122 aerobic glycolysis 105:122 Tumors utilize aerobic glycolysis to support growth and invasion. 27345396 0 26 theme breast 26:31 arg1 metastasis 40:49 breast cancer metastasis 26:49 breast cancer metastasis 26:49 O-GlcNAcylation regulates breast cancer metastasis via SIRT1 modulation of FOXM1 pathway. 27345396 7 27 theme MEK/ERK-dependent 875:891 arg1 manner 893:898 an MEK/ERK-dependent manner 872:898 an MEK/ERK-dependent manner 872:898 Reduced O-GlcNAcylation in cancer cells leads to SIRT1-mediated proteasomal degradation of oncogenic transcription factor FOXM1 in an MEK/ERK-dependent manner. 27345396 7 28 theme cancer 768:773 arg1 cells 775:779 cancer cells 768:779 cancer cells 768:779 Reduced O-GlcNAcylation in cancer cells leads to SIRT1-mediated proteasomal degradation of oncogenic transcription factor FOXM1 in an MEK/ERK-dependent manner. 27345396 9 29 theme OGT-mediated 1095:1106 arg1 regulation 1108:1117 OGT-mediated regulation 1095:1117 OGT-mediated regulation of invasion and metastasis in breast cancer cells 1095:1167 Moreover, we show that SIRT1 levels are required for OGT-mediated regulation of invasion and metastasis in breast cancer cells. 27345396 6 30 theme SIRT1 653:657 arg1 levels 659:664 SIRT1 levels 653:664 SIRT1 levels 653:664 Reducing O-GlcNAcylation elevates SIRT1 levels and activity in an AMPK (AMP-activated protein kinase α)-dependent manner. 27345396 3 31 theme O-linked-β-N-acetylglucosamine 270:299 arg1 OGT 325:327 OGT 325:327 OGT 325:327 The nutrient sensor O-linked-β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) modifies intracellular proteins with N-acetylglucosamine. 27345396 3 31 theme O-linked-β-N-acetylglucosamine 270:299 arg1 transferase 312:322 The nutrient sensor O-linked-β-N-acetylglucosamine (O-GlcNAc) transferase 250:322 The nutrient sensor O-linked-β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) 250:328 The nutrient sensor O-linked-β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) modifies intracellular proteins with N-acetylglucosamine. 27345396 6 32 theme -dependent 722:731 arg1 manner 733:738 an AMPK (AMP-activated protein kinase α)-dependent manner 682:738 an AMPK (AMP-activated protein kinase α)-dependent manner 682:738 Reducing O-GlcNAcylation elevates SIRT1 levels and activity in an AMPK (AMP-activated protein kinase α)-dependent manner. 27345396 2 33 theme molecular 169:177 arg1 mechanisms 179:188 the molecular mechanisms 165:188 the molecular mechanisms that link metabolism with invasion 165:223 However, the molecular mechanisms that link metabolism with invasion are not well understood. 27345396 5 34 theme NAD+-dependent 585:598 arg1 SIRT1 612:616 the NAD+-dependent deacetylase SIRT1 581:616 the NAD+-dependent deacetylase SIRT1 581:616 Here, we show that the regulation of cancer invasion by OGT is dependent on the NAD+-dependent deacetylase SIRT1. 27345396 9 35 theme SIRT1 1065:1069 arg1 levels 1071:1076 SIRT1 levels 1065:1076 SIRT1 levels 1065:1076 Moreover, we show that SIRT1 levels are required for OGT-mediated regulation of invasion and metastasis in breast cancer cells. 27345396 10 36 theme SIRT1/ERK/FOXM1 1268:1282 arg1 axis 1284:1287 an SIRT1/ERK/FOXM1 axis 1265:1287 an SIRT1/ERK/FOXM1 axis 1265:1287 Thus, O-GlcNAcylation is a central component linking metabolism to invasion and metastasis via an SIRT1/ERK/FOXM1 axis. 27345396 5 37 theme deacetylase 600:610 arg1 SIRT1 612:616 the NAD+-dependent deacetylase SIRT1 581:616 the NAD+-dependent deacetylase SIRT1 581:616 Here, we show that the regulation of cancer invasion by OGT is dependent on the NAD+-dependent deacetylase SIRT1. 27345396 0 38 theme SIRT1 55:59 arg1 modulation 61:70 SIRT1 modulation 55:70 SIRT1 modulation of FOXM1 pathway 55:87 O-GlcNAcylation regulates breast cancer metastasis via SIRT1 modulation of FOXM1 pathway. 27345396 7 39 theme factor 856:861 arg1 FOXM1 863:867 oncogenic transcription factor FOXM1 832:867 oncogenic transcription factor FOXM1 832:867 Reduced O-GlcNAcylation in cancer cells leads to SIRT1-mediated proteasomal degradation of oncogenic transcription factor FOXM1 in an MEK/ERK-dependent manner. 27345396 7 40 theme FOXM1 863:867 arg1 degradation 817:827 SIRT1-mediated proteasomal degradation 790:827 SIRT1-mediated proteasomal degradation of oncogenic transcription factor FOXM1 790:867 Reduced O-GlcNAcylation in cancer cells leads to SIRT1-mediated proteasomal degradation of oncogenic transcription factor FOXM1 in an MEK/ERK-dependent manner. 27345396 7 41 theme Reduced 741:747 arg1 O-GlcNAcylation 749:763 Reduced O-GlcNAcylation 741:763 Reduced O-GlcNAcylation in cancer cells 741:779 Reduced O-GlcNAcylation in cancer cells leads to SIRT1-mediated proteasomal degradation of oncogenic transcription factor FOXM1 in an MEK/ERK-dependent manner. 27345396 9 42 theme metastasis 1135:1144 arg1 regulation 1108:1117 OGT-mediated regulation 1095:1117 OGT-mediated regulation of invasion and metastasis in breast cancer cells 1095:1167 Moreover, we show that SIRT1 levels are required for OGT-mediated regulation of invasion and metastasis in breast cancer cells. 27345396 7 43 theme oncogenic 832:840 arg1 FOXM1 863:867 oncogenic transcription factor FOXM1 832:867 oncogenic transcription factor FOXM1 832:867 Reduced O-GlcNAcylation in cancer cells leads to SIRT1-mediated proteasomal degradation of oncogenic transcription factor FOXM1 in an MEK/ERK-dependent manner. 27345396 8 44 theme OGT-mediated 923:934 arg1 regulation 936:945 OGT-mediated regulation 923:945 OGT-mediated regulation of FOXM1 ubiquitination 923:969 SIRT1 is critical for OGT-mediated regulation of FOXM1 ubiquitination and reducing SIRT1 activity reverses OGT-mediated regulation of FOXM1. 27345396 7 45 theme transcription 842:854 arg1 FOXM1 863:867 oncogenic transcription factor FOXM1 832:867 oncogenic transcription factor FOXM1 832:867 Reduced O-GlcNAcylation in cancer cells leads to SIRT1-mediated proteasomal degradation of oncogenic transcription factor FOXM1 in an MEK/ERK-dependent manner. 27345396 0 46 theme FOXM1 75:79 arg1 pathway 81:87 FOXM1 pathway 75:87 FOXM1 pathway 75:87 O-GlcNAcylation regulates breast cancer metastasis via SIRT1 modulation of FOXM1 pathway. 27345396 3 47 with proteins 353:360 arg1 N-acetylglucosamine 367:385 N-acetylglucosamine 367:385 N-acetylglucosamine 367:385 The nutrient sensor O-linked-β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) modifies intracellular proteins with N-acetylglucosamine. 27345396 9 48 theme cancer 1156:1161 arg1 cells 1163:1167 breast cancer cells 1149:1167 breast cancer cells 1149:1167 Moreover, we show that SIRT1 levels are required for OGT-mediated regulation of invasion and metastasis in breast cancer cells. 27345396 6 49 theme protein 705:711 arg1 kinase 713:718 AMP-activated protein kinase α 691:720 AMP-activated protein kinase α 691:720 Reducing O-GlcNAcylation elevates SIRT1 levels and activity in an AMPK (AMP-activated protein kinase α)-dependent manner. 27345396 9 50 theme breast 1149:1154 arg1 cells 1163:1167 breast cancer cells 1149:1167 breast cancer cells 1149:1167 Moreover, we show that SIRT1 levels are required for OGT-mediated regulation of invasion and metastasis in breast cancer cells. 27345396 6 51 theme AMP-activated 691:703 arg1 kinase 713:718 AMP-activated protein kinase α 691:720 AMP-activated protein kinase α 691:720 Reducing O-GlcNAcylation elevates SIRT1 levels and activity in an AMPK (AMP-activated protein kinase α)-dependent manner. 28973823 13 0 theme patients 1812:1819 arg1 due 1830:1832 due 1830:1832 due 1830:1832 Collectively, the higher colon cancer risk of diabetic patients could be due to O-GlcNAcylation-mediated AMPK inactivation and subsequent activation of mTOR. 28973823 13 0 theme patients 1812:1819 arg1 risk 1795:1798 the higher colon cancer risk 1771:1798 the higher colon cancer risk of diabetic patients 1771:1819 Collectively, the higher colon cancer risk of diabetic patients could be due to O-GlcNAcylation-mediated AMPK inactivation and subsequent activation of mTOR. 28973823 11 1 theme TMG 1539:1541 arg1 Injection 1526:1534 Injection 1526:1534 Injection of TMG 1526:1541 Injection of TMG promoted the growth and enhanced O-GlcNAcylation of the tumors of the mice. 28973823 12 2 theme mTOR 1751:1754 arg1 activation 1737:1746 activation 1737:1746 activation of mTOR 1737:1754 Consistent with in vitro data, AMPK O-GlcNAcylation was increased, which reduced AMPK phosphorylation and resulted in activation of mTOR. 28973823 13 3 theme higher 1775:1780 arg1 due 1830:1832 due 1830:1832 due 1830:1832 Collectively, the higher colon cancer risk of diabetic patients could be due to O-GlcNAcylation-mediated AMPK inactivation and subsequent activation of mTOR. 28973823 13 3 theme higher 1775:1780 arg1 risk 1795:1798 the higher colon cancer risk 1771:1798 the higher colon cancer risk of diabetic patients 1771:1819 Collectively, the higher colon cancer risk of diabetic patients could be due to O-GlcNAcylation-mediated AMPK inactivation and subsequent activation of mTOR. 28973823 4 4 theme O-GlcNAcylation 673:687 arg1 involvement 653:663 the involvement 649:663 the involvement of AMPK O-GlcNAcylation on the growth of LoVo cells, a human colon cancer cell line 649:747 Given that AMP-activated kinase (AMPK) has been thought to play important roles in suppressing tumor growth, we evaluated the involvement of AMPK O-GlcNAcylation on the growth of LoVo cells, a human colon cancer cell line. 28973823 13 5 theme cancer 1788:1793 arg1 due 1830:1832 due 1830:1832 due 1830:1832 Collectively, the higher colon cancer risk of diabetic patients could be due to O-GlcNAcylation-mediated AMPK inactivation and subsequent activation of mTOR. 28973823 13 5 theme cancer 1788:1793 arg1 risk 1795:1798 the higher colon cancer risk 1771:1798 the higher colon cancer risk of diabetic patients 1771:1819 Collectively, the higher colon cancer risk of diabetic patients could be due to O-GlcNAcylation-mediated AMPK inactivation and subsequent activation of mTOR. 28973823 10 6 theme O-GlcNAcylation 1426:1440 arg1 effects 1410:1416 the effects 1406:1416 the effects of AMPK O-GlcNAcylation 1406:1440 To examine the effects of AMPK O-GlcNAcylation in vivo, the LoVo cells were s.c. transplanted onto the backs of BALB/c-nu/nu mice. 28973823 2 7 theme essential 316:324 arg1 modification 345:356 an essential post-translational modification 313:356 an essential post-translational modification that is upregulated in diabetic patients and has been implicated in tumor growth 313:437 O-linked N-acetylglucosamine (O-GlcNAc) modification of proteins at serine/threonine residues (O-GlcNAcylation) is an essential post-translational modification that is upregulated in diabetic patients and has been implicated in tumor growth. 28973823 2 7 theme essential 316:324 arg1 modification 238:249 O-linked N-acetylglucosamine (O-GlcNAc) modification 198:249 O-linked N-acetylglucosamine (O-GlcNAc) modification of proteins at serine/threonine residues (O-GlcNAcylation) 198:308 O-linked N-acetylglucosamine (O-GlcNAc) modification of proteins at serine/threonine residues (O-GlcNAcylation) is an essential post-translational modification that is upregulated in diabetic patients and has been implicated in tumor growth. 28973823 1 8 theme diabetic 179:186 arg1 patients 188:195 diabetic patients 179:195 diabetic patients 179:195 Increasing incidence of various cancers has been reported in diabetic patients. 28973823 7 9 theme AMPK 1073:1076 arg1 phosphorylation 1078:1092 reduced AMPK phosphorylation 1065:1092 reduced AMPK phosphorylation 1065:1092 These treatments increased AMPK O-GlcNAcylation in a dose-dependent manner, which led to reduced AMPK phosphorylation and mTOR activation. 28973823 7 10 theme dose-dependent 1029:1042 arg1 manner 1044:1049 a dose-dependent manner 1027:1049 a dose-dependent manner 1027:1049 These treatments increased AMPK O-GlcNAcylation in a dose-dependent manner, which led to reduced AMPK phosphorylation and mTOR activation. 28973823 5 11 theme hydrolase 829:837 arg1 G 795:795 Thiamet G 787:795 Thiamet G (TMG) 787:801 Results revealed that treatment with Thiamet G (TMG), an inhibitor of O-GlcNAc hydrolase, increased both anchorage-dependent and -independent growth of the cells. 28973823 5 11 theme hydrolase 829:837 arg1 inhibitor 807:815 an inhibitor 804:815 an inhibitor of O-GlcNAc hydrolase 804:837 Results revealed that treatment with Thiamet G (TMG), an inhibitor of O-GlcNAc hydrolase, increased both anchorage-dependent and -independent growth of the cells. 28973823 5 12 theme cells 906:910 arg1 growth 892:897 both anchorage-dependent and -independent growth 850:897 both anchorage-dependent and -independent growth of the cells 850:910 Results revealed that treatment with Thiamet G (TMG), an inhibitor of O-GlcNAc hydrolase, increased both anchorage-dependent and -independent growth of the cells. 28973823 12 13 theme AMPK 1700:1703 arg1 phosphorylation 1705:1719 AMPK phosphorylation 1700:1719 AMPK phosphorylation 1700:1719 Consistent with in vitro data, AMPK O-GlcNAcylation was increased, which reduced AMPK phosphorylation and resulted in activation of mTOR. 28973823 6 14 theme transferase 922:932 arg1 overexpression 934:947 O-GlcNAc transferase overexpression 913:947 O-GlcNAc transferase overexpression 913:947 O-GlcNAc transferase overexpression also increased the growth. 28973823 4 15 theme colon 726:730 arg1 line 744:747 human colon cancer cell line 720:747 a human colon cancer cell line 718:747 Given that AMP-activated kinase (AMPK) has been thought to play important roles in suppressing tumor growth, we evaluated the involvement of AMPK O-GlcNAcylation on the growth of LoVo cells, a human colon cancer cell line. 28973823 4 15 theme colon 726:730 arg1 cells 711:715 LoVo cells 706:715 LoVo cells 706:715 Given that AMP-activated kinase (AMPK) has been thought to play important roles in suppressing tumor growth, we evaluated the involvement of AMPK O-GlcNAcylation on the growth of LoVo cells, a human colon cancer cell line. 28973823 7 16 theme AMPK 1003:1006 arg1 O-GlcNAcylation 1008:1022 AMPK O-GlcNAcylation 1003:1022 AMPK O-GlcNAcylation 1003:1022 These treatments increased AMPK O-GlcNAcylation in a dose-dependent manner, which led to reduced AMPK phosphorylation and mTOR activation. 28973823 5 17 theme Thiamet 787:793 arg1 G 795:795 Thiamet G 787:795 Thiamet G (TMG) 787:801 Results revealed that treatment with Thiamet G (TMG), an inhibitor of O-GlcNAc hydrolase, increased both anchorage-dependent and -independent growth of the cells. 28973823 5 17 theme Thiamet 787:793 arg1 inhibitor 807:815 an inhibitor 804:815 an inhibitor of O-GlcNAc hydrolase 804:837 Results revealed that treatment with Thiamet G (TMG), an inhibitor of O-GlcNAc hydrolase, increased both anchorage-dependent and -independent growth of the cells. 28973823 5 17 theme Thiamet 787:793 arg1 TMG 798:800 TMG 798:800 TMG 798:800 Results revealed that treatment with Thiamet G (TMG), an inhibitor of O-GlcNAc hydrolase, increased both anchorage-dependent and -independent growth of the cells. 28973823 5 18 theme -independent 879:890 arg1 growth 892:897 both anchorage-dependent and -independent growth 850:897 both anchorage-dependent and -independent growth of the cells 850:910 Results revealed that treatment with Thiamet G (TMG), an inhibitor of O-GlcNAc hydrolase, increased both anchorage-dependent and -independent growth of the cells. 28973823 8 19 with consistent 1219:1228 arg1 inhibition 1257:1266 genetic inhibition 1249:1266 genetic inhibition of AMPK 1249:1274 Chemical inhibition or activation of AMPK led to increased or decreased growth, respectively, which was consistent with the data with genetic inhibition of AMPK. 28973823 8 19 with consistent 1219:1228 arg1 data 1239:1242 the data 1235:1242 the data 1235:1242 Chemical inhibition or activation of AMPK led to increased or decreased growth, respectively, which was consistent with the data with genetic inhibition of AMPK. 28973823 4 20 theme cells 711:715 arg1 growth 696:701 the growth 692:701 the growth of LoVo cells, a human colon cancer cell line 692:747 Given that AMP-activated kinase (AMPK) has been thought to play important roles in suppressing tumor growth, we evaluated the involvement of AMPK O-GlcNAcylation on the growth of LoVo cells, a human colon cancer cell line. 28973823 0 21 theme cells 85:89 arg1 proliferation 63:75 the proliferation 59:75 the proliferation of LoVo cells, a colon cancer cell line 59:115 Augmented O-GlcNAcylation of AMP-activated kinase promotes the proliferation of LoVo cells, a colon cancer cell line. 28973823 4 22 theme AMP-activated 538:550 arg1 AMPK 560:563 AMPK 560:563 AMPK 560:563 Given that AMP-activated kinase (AMPK) has been thought to play important roles in suppressing tumor growth, we evaluated the involvement of AMPK O-GlcNAcylation on the growth of LoVo cells, a human colon cancer cell line. 28973823 4 22 theme AMP-activated 538:550 arg1 kinase 552:557 AMP-activated kinase 538:557 AMP-activated kinase (AMPK) 538:564 Given that AMP-activated kinase (AMPK) has been thought to play important roles in suppressing tumor growth, we evaluated the involvement of AMPK O-GlcNAcylation on the growth of LoVo cells, a human colon cancer cell line. 28973823 13 23 theme mTOR 1909:1912 arg1 inactivation 1867:1878 O-GlcNAcylation-mediated AMPK inactivation 1837:1878 O-GlcNAcylation-mediated AMPK inactivation 1837:1878 Collectively, the higher colon cancer risk of diabetic patients could be due to O-GlcNAcylation-mediated AMPK inactivation and subsequent activation of mTOR. 28973823 13 23 theme mTOR 1909:1912 arg1 activation 1895:1904 subsequent activation 1884:1904 subsequent activation of mTOR 1884:1912 Collectively, the higher colon cancer risk of diabetic patients could be due to O-GlcNAcylation-mediated AMPK inactivation and subsequent activation of mTOR. 28973823 10 24 dep transplanted 1476:1487 arg1 s.c. 1471:1474 s.c. 1471:1474 s.c. 1471:1474 To examine the effects of AMPK O-GlcNAcylation in vivo, the LoVo cells were s.c. transplanted onto the backs of BALB/c-nu/nu mice. 28973823 9 25 theme tumor 1319:1323 arg1 growth 1325:1330 tumor growth 1319:1330 tumor growth 1319:1330 In addition, TMG-mediated acceleration of tumor growth was abolished by both chemical and genetic inhibition of AMPK. 28973823 13 26 theme AMPK 1862:1865 arg1 inactivation 1867:1878 O-GlcNAcylation-mediated AMPK inactivation 1837:1878 O-GlcNAcylation-mediated AMPK inactivation 1837:1878 Collectively, the higher colon cancer risk of diabetic patients could be due to O-GlcNAcylation-mediated AMPK inactivation and subsequent activation of mTOR. 28973823 0 27 theme cancer 100:105 arg1 cells 85:89 LoVo cells 80:89 LoVo cells 80:89 Augmented O-GlcNAcylation of AMP-activated kinase promotes the proliferation of LoVo cells, a colon cancer cell line. 28973823 0 27 theme cancer 100:105 arg1 line 112:115 colon cancer cell line 94:115 a colon cancer cell line 92:115 Augmented O-GlcNAcylation of AMP-activated kinase promotes the proliferation of LoVo cells, a colon cancer cell line. 28973823 4 28 theme cell 739:742 arg1 line 744:747 human colon cancer cell line 720:747 a human colon cancer cell line 718:747 Given that AMP-activated kinase (AMPK) has been thought to play important roles in suppressing tumor growth, we evaluated the involvement of AMPK O-GlcNAcylation on the growth of LoVo cells, a human colon cancer cell line. 28973823 4 28 theme cell 739:742 arg1 cells 711:715 LoVo cells 706:715 LoVo cells 706:715 Given that AMP-activated kinase (AMPK) has been thought to play important roles in suppressing tumor growth, we evaluated the involvement of AMPK O-GlcNAcylation on the growth of LoVo cells, a human colon cancer cell line. 28973823 0 29 theme Augmented 0:8 arg1 O-GlcNAcylation 10:24 Augmented O-GlcNAcylation 0:24 Augmented O-GlcNAcylation of AMP-activated kinase 0:48 Augmented O-GlcNAcylation of AMP-activated kinase promotes the proliferation of LoVo cells, a colon cancer cell line. 28973823 7 30 dep increased 993:1001 arg1 led 1058:1060 led 1058:1060 led to reduced AMPK phosphorylation and mTOR activation 1058:1112 These treatments increased AMPK O-GlcNAcylation in a dose-dependent manner, which led to reduced AMPK phosphorylation and mTOR activation. 28973823 9 31 theme chemical 1354:1361 arg1 inhibition 1375:1384 both chemical and genetic inhibition 1349:1384 both chemical and genetic inhibition of AMPK 1349:1392 In addition, TMG-mediated acceleration of tumor growth was abolished by both chemical and genetic inhibition of AMPK. 28973823 8 32 theme genetic 1249:1255 arg1 inhibition 1257:1266 genetic inhibition 1249:1266 genetic inhibition of AMPK 1249:1274 Chemical inhibition or activation of AMPK led to increased or decreased growth, respectively, which was consistent with the data with genetic inhibition of AMPK. 28973823 9 33 theme genetic 1367:1373 arg1 inhibition 1375:1384 both chemical and genetic inhibition 1349:1384 both chemical and genetic inhibition of AMPK 1349:1392 In addition, TMG-mediated acceleration of tumor growth was abolished by both chemical and genetic inhibition of AMPK. 28973823 0 34 theme kinase 43:48 arg1 O-GlcNAcylation 10:24 Augmented O-GlcNAcylation 0:24 Augmented O-GlcNAcylation of AMP-activated kinase 0:48 Augmented O-GlcNAcylation of AMP-activated kinase promotes the proliferation of LoVo cells, a colon cancer cell line. 28973823 11 35 theme tumors 1599:1604 arg1 growth 1556:1561 growth 1556:1561 growth 1556:1561 Injection of TMG promoted the growth and enhanced O-GlcNAcylation of the tumors of the mice. 28973823 11 35 theme tumors 1599:1604 arg1 O-GlcNAcylation 1576:1590 enhanced O-GlcNAcylation 1567:1590 enhanced O-GlcNAcylation 1567:1590 Injection of TMG promoted the growth and enhanced O-GlcNAcylation of the tumors of the mice. 28973823 10 36 theme BALB/c-nu/nu 1507:1518 arg1 mice 1520:1523 BALB/c-nu/nu mice 1507:1523 BALB/c-nu/nu mice 1507:1523 To examine the effects of AMPK O-GlcNAcylation in vivo, the LoVo cells were s.c. transplanted onto the backs of BALB/c-nu/nu mice. 28973823 2 37 theme O-linked 198:205 arg1 O-GlcNAc 228:235 O-GlcNAc 228:235 O-GlcNAc 228:235 O-linked N-acetylglucosamine (O-GlcNAc) modification of proteins at serine/threonine residues (O-GlcNAcylation) is an essential post-translational modification that is upregulated in diabetic patients and has been implicated in tumor growth. 28973823 2 37 theme O-linked 198:205 arg1 N-acetylglucosamine 207:225 O-linked N-acetylglucosamine 198:225 O-linked N-acetylglucosamine (O-GlcNAc) modification of proteins at serine/threonine residues (O-GlcNAcylation) 198:308 O-linked N-acetylglucosamine (O-GlcNAc) modification of proteins at serine/threonine residues (O-GlcNAcylation) is an essential post-translational modification that is upregulated in diabetic patients and has been implicated in tumor growth. 28973823 1 38 theme various 142:148 arg1 cancers 150:156 various cancers 142:156 various cancers 142:156 Increasing incidence of various cancers has been reported in diabetic patients. 28973823 4 39 theme tumor 622:626 arg1 growth 628:633 tumor growth 622:633 tumor growth 622:633 Given that AMP-activated kinase (AMPK) has been thought to play important roles in suppressing tumor growth, we evaluated the involvement of AMPK O-GlcNAcylation on the growth of LoVo cells, a human colon cancer cell line. 28973823 2 40 link O-linked 198:205 arg1 O-GlcNAc 228:235 O-GlcNAc 228:235 O-GlcNAc 228:235 O-linked N-acetylglucosamine (O-GlcNAc) modification of proteins at serine/threonine residues (O-GlcNAcylation) is an essential post-translational modification that is upregulated in diabetic patients and has been implicated in tumor growth. 28973823 2 40 link O-linked 198:205 arg1 N-acetylglucosamine 207:225 O-linked N-acetylglucosamine 198:225 O-linked N-acetylglucosamine (O-GlcNAc) modification of proteins at serine/threonine residues (O-GlcNAcylation) 198:308 O-linked N-acetylglucosamine (O-GlcNAc) modification of proteins at serine/threonine residues (O-GlcNAcylation) is an essential post-translational modification that is upregulated in diabetic patients and has been implicated in tumor growth. 28973823 8 41 theme AMPK 1152:1155 arg1 activation 1138:1147 activation 1138:1147 activation of AMPK 1138:1155 Chemical inhibition or activation of AMPK led to increased or decreased growth, respectively, which was consistent with the data with genetic inhibition of AMPK. 28973823 8 41 theme AMPK 1152:1155 arg1 inhibition 1124:1133 Chemical inhibition 1115:1133 Chemical inhibition 1115:1133 Chemical inhibition or activation of AMPK led to increased or decreased growth, respectively, which was consistent with the data with genetic inhibition of AMPK. 28973823 6 42 theme O-GlcNAc 913:920 arg1 overexpression 934:947 O-GlcNAc transferase overexpression 913:947 O-GlcNAc transferase overexpression 913:947 O-GlcNAc transferase overexpression also increased the growth. 28973823 12 43 with Consistent 1619:1628 arg1 data 1644:1647 in vitro data 1635:1647 in vitro data 1635:1647 Consistent with in vitro data, AMPK O-GlcNAcylation was increased, which reduced AMPK phosphorylation and resulted in activation of mTOR. 28973823 13 44 theme diabetic 1803:1810 arg1 patients 1812:1819 diabetic patients 1803:1819 diabetic patients 1803:1819 Collectively, the higher colon cancer risk of diabetic patients could be due to O-GlcNAcylation-mediated AMPK inactivation and subsequent activation of mTOR. 28973823 2 45 theme diabetic 381:388 arg1 patients 390:397 diabetic patients 381:397 diabetic patients 381:397 O-linked N-acetylglucosamine (O-GlcNAc) modification of proteins at serine/threonine residues (O-GlcNAcylation) is an essential post-translational modification that is upregulated in diabetic patients and has been implicated in tumor growth. 28973823 4 46 theme important 591:599 arg1 roles 601:605 important roles 591:605 important roles 591:605 Given that AMP-activated kinase (AMPK) has been thought to play important roles in suppressing tumor growth, we evaluated the involvement of AMPK O-GlcNAcylation on the growth of LoVo cells, a human colon cancer cell line. 28973823 10 47 theme AMPK 1421:1424 arg1 O-GlcNAcylation 1426:1440 AMPK O-GlcNAcylation 1421:1440 AMPK O-GlcNAcylation 1421:1440 To examine the effects of AMPK O-GlcNAcylation in vivo, the LoVo cells were s.c. transplanted onto the backs of BALB/c-nu/nu mice. 28973823 12 48 dep in 1635:1636 arg1 vitro 1638:1642 vitro 1638:1642 vitro 1638:1642 Consistent with in vitro data, AMPK O-GlcNAcylation was increased, which reduced AMPK phosphorylation and resulted in activation of mTOR. 28973823 13 49 theme colon 1782:1786 arg1 due 1830:1832 due 1830:1832 due 1830:1832 Collectively, the higher colon cancer risk of diabetic patients could be due to O-GlcNAcylation-mediated AMPK inactivation and subsequent activation of mTOR. 28973823 13 49 theme colon 1782:1786 arg1 risk 1795:1798 the higher colon cancer risk 1771:1798 the higher colon cancer risk of diabetic patients 1771:1819 Collectively, the higher colon cancer risk of diabetic patients could be due to O-GlcNAcylation-mediated AMPK inactivation and subsequent activation of mTOR. 28973823 4 50 theme AMPK 668:671 arg1 O-GlcNAcylation 673:687 AMPK O-GlcNAcylation 668:687 AMPK O-GlcNAcylation 668:687 Given that AMP-activated kinase (AMPK) has been thought to play important roles in suppressing tumor growth, we evaluated the involvement of AMPK O-GlcNAcylation on the growth of LoVo cells, a human colon cancer cell line. 28973823 7 51 theme mTOR 1098:1101 arg1 activation 1103:1112 mTOR activation 1098:1112 mTOR activation 1098:1112 These treatments increased AMPK O-GlcNAcylation in a dose-dependent manner, which led to reduced AMPK phosphorylation and mTOR activation. 28973823 11 52 theme enhanced 1567:1574 arg1 O-GlcNAcylation 1576:1590 enhanced O-GlcNAcylation 1567:1590 enhanced O-GlcNAcylation 1567:1590 Injection of TMG promoted the growth and enhanced O-GlcNAcylation of the tumors of the mice. 28973823 2 53 theme post-translational 326:343 arg1 modification 345:356 an essential post-translational modification 313:356 an essential post-translational modification that is upregulated in diabetic patients and has been implicated in tumor growth 313:437 O-linked N-acetylglucosamine (O-GlcNAc) modification of proteins at serine/threonine residues (O-GlcNAcylation) is an essential post-translational modification that is upregulated in diabetic patients and has been implicated in tumor growth. 28973823 2 53 theme post-translational 326:343 arg1 modification 238:249 O-linked N-acetylglucosamine (O-GlcNAc) modification 198:249 O-linked N-acetylglucosamine (O-GlcNAc) modification of proteins at serine/threonine residues (O-GlcNAcylation) 198:308 O-linked N-acetylglucosamine (O-GlcNAc) modification of proteins at serine/threonine residues (O-GlcNAcylation) is an essential post-translational modification that is upregulated in diabetic patients and has been implicated in tumor growth. 28973823 4 54 from involvement 653:663 arg1 growth 696:701 the growth 692:701 the growth of LoVo cells, a human colon cancer cell line 692:747 Given that AMP-activated kinase (AMPK) has been thought to play important roles in suppressing tumor growth, we evaluated the involvement of AMPK O-GlcNAcylation on the growth of LoVo cells, a human colon cancer cell line. 28973823 8 55 theme AMPK 1271:1274 arg1 inhibition 1257:1266 genetic inhibition 1249:1266 genetic inhibition of AMPK 1249:1274 Chemical inhibition or activation of AMPK led to increased or decreased growth, respectively, which was consistent with the data with genetic inhibition of AMPK. 28973823 7 56 theme reduced 1065:1071 arg1 phosphorylation 1078:1092 reduced AMPK phosphorylation 1065:1092 reduced AMPK phosphorylation 1065:1092 These treatments increased AMPK O-GlcNAcylation in a dose-dependent manner, which led to reduced AMPK phosphorylation and mTOR activation. 28973823 5 57 theme anchorage-dependent 855:873 arg1 growth 892:897 both anchorage-dependent and -independent growth 850:897 both anchorage-dependent and -independent growth of the cells 850:910 Results revealed that treatment with Thiamet G (TMG), an inhibitor of O-GlcNAc hydrolase, increased both anchorage-dependent and -independent growth of the cells. 28973823 5 58 theme O-GlcNAc 820:827 arg1 hydrolase 829:837 O-GlcNAc hydrolase 820:837 O-GlcNAc hydrolase 820:837 Results revealed that treatment with Thiamet G (TMG), an inhibitor of O-GlcNAc hydrolase, increased both anchorage-dependent and -independent growth of the cells. 28973823 2 59 theme serine/threonine 266:281 arg1 O-GlcNAcylation 293:307 O-GlcNAcylation 293:307 O-GlcNAcylation 293:307 O-linked N-acetylglucosamine (O-GlcNAc) modification of proteins at serine/threonine residues (O-GlcNAcylation) is an essential post-translational modification that is upregulated in diabetic patients and has been implicated in tumor growth. 28973823 2 59 theme serine/threonine 266:281 arg1 residues 283:290 serine/threonine residues 266:290 serine/threonine residues (O-GlcNAcylation) 266:308 O-linked N-acetylglucosamine (O-GlcNAc) modification of proteins at serine/threonine residues (O-GlcNAcylation) is an essential post-translational modification that is upregulated in diabetic patients and has been implicated in tumor growth. 28973823 2 60 mod modification 238:249 arg1 proteins 254:261 proteins 254:261 proteins 254:261 O-linked N-acetylglucosamine (O-GlcNAc) modification of proteins at serine/threonine residues (O-GlcNAcylation) is an essential post-translational modification that is upregulated in diabetic patients and has been implicated in tumor growth. 28973823 2 60 mod modification 238:249 arg3 O-GlcNAc 228:235 O-GlcNAc 228:235 O-GlcNAc 228:235 O-linked N-acetylglucosamine (O-GlcNAc) modification of proteins at serine/threonine residues (O-GlcNAcylation) is an essential post-translational modification that is upregulated in diabetic patients and has been implicated in tumor growth. 28973823 2 60 mod modification 238:249 arg3 N-acetylglucosamine 207:225 O-linked N-acetylglucosamine 198:225 O-linked N-acetylglucosamine (O-GlcNAc) modification of proteins at serine/threonine residues (O-GlcNAcylation) 198:308 O-linked N-acetylglucosamine (O-GlcNAc) modification of proteins at serine/threonine residues (O-GlcNAcylation) is an essential post-translational modification that is upregulated in diabetic patients and has been implicated in tumor growth. 28973823 1 61 theme Increasing 118:127 arg1 incidence 129:137 Increasing incidence 118:137 Increasing incidence of various cancers 118:156 Increasing incidence of various cancers has been reported in diabetic patients. 28973823 2 62 from residues 283:290 arg1 modification 345:356 an essential post-translational modification 313:356 an essential post-translational modification that is upregulated in diabetic patients and has been implicated in tumor growth 313:437 O-linked N-acetylglucosamine (O-GlcNAc) modification of proteins at serine/threonine residues (O-GlcNAcylation) is an essential post-translational modification that is upregulated in diabetic patients and has been implicated in tumor growth. 28973823 2 62 from residues 283:290 arg1 modification 238:249 O-linked N-acetylglucosamine (O-GlcNAc) modification 198:249 O-linked N-acetylglucosamine (O-GlcNAc) modification of proteins at serine/threonine residues (O-GlcNAcylation) 198:308 O-linked N-acetylglucosamine (O-GlcNAc) modification of proteins at serine/threonine residues (O-GlcNAcylation) is an essential post-translational modification that is upregulated in diabetic patients and has been implicated in tumor growth. 28973823 5 63 with treatment 772:780 arg1 G 795:795 Thiamet G 787:795 Thiamet G (TMG) 787:801 Results revealed that treatment with Thiamet G (TMG), an inhibitor of O-GlcNAc hydrolase, increased both anchorage-dependent and -independent growth of the cells. 28973823 5 63 with treatment 772:780 arg1 inhibitor 807:815 an inhibitor 804:815 an inhibitor of O-GlcNAc hydrolase 804:837 Results revealed that treatment with Thiamet G (TMG), an inhibitor of O-GlcNAc hydrolase, increased both anchorage-dependent and -independent growth of the cells. 28973823 5 63 with treatment 772:780 arg1 TMG 798:800 TMG 798:800 TMG 798:800 Results revealed that treatment with Thiamet G (TMG), an inhibitor of O-GlcNAc hydrolase, increased both anchorage-dependent and -independent growth of the cells. 28973823 4 64 theme human 720:724 arg1 line 744:747 human colon cancer cell line 720:747 a human colon cancer cell line 718:747 Given that AMP-activated kinase (AMPK) has been thought to play important roles in suppressing tumor growth, we evaluated the involvement of AMPK O-GlcNAcylation on the growth of LoVo cells, a human colon cancer cell line. 28973823 4 64 theme human 720:724 arg1 cells 711:715 LoVo cells 706:715 LoVo cells 706:715 Given that AMP-activated kinase (AMPK) has been thought to play important roles in suppressing tumor growth, we evaluated the involvement of AMPK O-GlcNAcylation on the growth of LoVo cells, a human colon cancer cell line. 28973823 0 65 theme LoVo 80:83 arg1 cells 85:89 LoVo cells 80:89 LoVo cells 80:89 Augmented O-GlcNAcylation of AMP-activated kinase promotes the proliferation of LoVo cells, a colon cancer cell line. 28973823 0 65 theme LoVo 80:83 arg1 line 112:115 colon cancer cell line 94:115 a colon cancer cell line 92:115 Augmented O-GlcNAcylation of AMP-activated kinase promotes the proliferation of LoVo cells, a colon cancer cell line. 28973823 2 66 theme proteins 254:261 arg1 modification 345:356 an essential post-translational modification 313:356 an essential post-translational modification that is upregulated in diabetic patients and has been implicated in tumor growth 313:437 O-linked N-acetylglucosamine (O-GlcNAc) modification of proteins at serine/threonine residues (O-GlcNAcylation) is an essential post-translational modification that is upregulated in diabetic patients and has been implicated in tumor growth. 28973823 2 66 theme proteins 254:261 arg1 modification 238:249 O-linked N-acetylglucosamine (O-GlcNAc) modification 198:249 O-linked N-acetylglucosamine (O-GlcNAc) modification of proteins at serine/threonine residues (O-GlcNAcylation) 198:308 O-linked N-acetylglucosamine (O-GlcNAc) modification of proteins at serine/threonine residues (O-GlcNAcylation) is an essential post-translational modification that is upregulated in diabetic patients and has been implicated in tumor growth. 28973823 13 67 theme subsequent 1884:1893 arg1 activation 1895:1904 subsequent activation 1884:1904 subsequent activation of mTOR 1884:1912 Collectively, the higher colon cancer risk of diabetic patients could be due to O-GlcNAcylation-mediated AMPK inactivation and subsequent activation of mTOR. 28973823 9 68 theme TMG-mediated 1290:1301 arg1 acceleration 1303:1314 TMG-mediated acceleration 1290:1314 TMG-mediated acceleration of tumor growth 1290:1330 In addition, TMG-mediated acceleration of tumor growth was abolished by both chemical and genetic inhibition of AMPK. 28973823 1 69 theme cancers 150:156 arg1 incidence 129:137 Increasing incidence 118:137 Increasing incidence of various cancers 118:156 Increasing incidence of various cancers has been reported in diabetic patients. 28973823 4 70 theme LoVo 706:709 arg1 line 744:747 human colon cancer cell line 720:747 a human colon cancer cell line 718:747 Given that AMP-activated kinase (AMPK) has been thought to play important roles in suppressing tumor growth, we evaluated the involvement of AMPK O-GlcNAcylation on the growth of LoVo cells, a human colon cancer cell line. 28973823 4 70 theme LoVo 706:709 arg1 cells 711:715 LoVo cells 706:715 LoVo cells 706:715 Given that AMP-activated kinase (AMPK) has been thought to play important roles in suppressing tumor growth, we evaluated the involvement of AMPK O-GlcNAcylation on the growth of LoVo cells, a human colon cancer cell line. 28973823 0 71 theme colon 94:98 arg1 cells 85:89 LoVo cells 80:89 LoVo cells 80:89 Augmented O-GlcNAcylation of AMP-activated kinase promotes the proliferation of LoVo cells, a colon cancer cell line. 28973823 0 71 theme colon 94:98 arg1 line 112:115 colon cancer cell line 94:115 a colon cancer cell line 92:115 Augmented O-GlcNAcylation of AMP-activated kinase promotes the proliferation of LoVo cells, a colon cancer cell line. 28973823 13 72 theme O-GlcNAcylation-mediated 1837:1860 arg1 inactivation 1867:1878 O-GlcNAcylation-mediated AMPK inactivation 1837:1878 O-GlcNAcylation-mediated AMPK inactivation 1837:1878 Collectively, the higher colon cancer risk of diabetic patients could be due to O-GlcNAcylation-mediated AMPK inactivation and subsequent activation of mTOR. 28973823 0 73 theme cell 107:110 arg1 cells 85:89 LoVo cells 80:89 LoVo cells 80:89 Augmented O-GlcNAcylation of AMP-activated kinase promotes the proliferation of LoVo cells, a colon cancer cell line. 28973823 0 73 theme cell 107:110 arg1 line 112:115 colon cancer cell line 94:115 a colon cancer cell line 92:115 Augmented O-GlcNAcylation of AMP-activated kinase promotes the proliferation of LoVo cells, a colon cancer cell line. 28973823 9 74 theme growth 1325:1330 arg1 acceleration 1303:1314 TMG-mediated acceleration 1290:1314 TMG-mediated acceleration of tumor growth 1290:1330 In addition, TMG-mediated acceleration of tumor growth was abolished by both chemical and genetic inhibition of AMPK. 28973823 12 75 theme AMPK 1650:1653 arg1 O-GlcNAcylation 1655:1669 AMPK O-GlcNAcylation 1650:1669 AMPK O-GlcNAcylation 1650:1669 Consistent with in vitro data, AMPK O-GlcNAcylation was increased, which reduced AMPK phosphorylation and resulted in activation of mTOR. 28973823 10 76 theme LoVo 1455:1458 arg1 cells 1460:1464 the LoVo cells 1451:1464 the LoVo cells 1451:1464 To examine the effects of AMPK O-GlcNAcylation in vivo, the LoVo cells were s.c. transplanted onto the backs of BALB/c-nu/nu mice. 28973823 4 77 theme cancer 732:737 arg1 line 744:747 human colon cancer cell line 720:747 a human colon cancer cell line 718:747 Given that AMP-activated kinase (AMPK) has been thought to play important roles in suppressing tumor growth, we evaluated the involvement of AMPK O-GlcNAcylation on the growth of LoVo cells, a human colon cancer cell line. 28973823 4 77 theme cancer 732:737 arg1 cells 711:715 LoVo cells 706:715 LoVo cells 706:715 Given that AMP-activated kinase (AMPK) has been thought to play important roles in suppressing tumor growth, we evaluated the involvement of AMPK O-GlcNAcylation on the growth of LoVo cells, a human colon cancer cell line. 28973823 0 78 theme AMP-activated 29:41 arg1 kinase 43:48 AMP-activated kinase 29:48 AMP-activated kinase 29:48 Augmented O-GlcNAcylation of AMP-activated kinase promotes the proliferation of LoVo cells, a colon cancer cell line. 28973823 3 79 theme tumor 498:502 arg1 growth 504:509 tumor growth 498:509 tumor growth 498:509 However, the mechanisms by which O-GlcNAcylation promotes tumor growth remain unclear. 28973823 8 80 theme Chemical 1115:1122 arg1 inhibition 1124:1133 Chemical inhibition 1115:1133 Chemical inhibition 1115:1133 Chemical inhibition or activation of AMPK led to increased or decreased growth, respectively, which was consistent with the data with genetic inhibition of AMPK. 28973823 12 81 theme in 1635:1636 arg1 data 1644:1647 in vitro data 1635:1647 in vitro data 1635:1647 Consistent with in vitro data, AMPK O-GlcNAcylation was increased, which reduced AMPK phosphorylation and resulted in activation of mTOR. 28973823 2 82 theme tumor 426:430 arg1 growth 432:437 tumor growth 426:437 tumor growth 426:437 O-linked N-acetylglucosamine (O-GlcNAc) modification of proteins at serine/threonine residues (O-GlcNAcylation) is an essential post-translational modification that is upregulated in diabetic patients and has been implicated in tumor growth. 28973823 10 83 theme mice 1520:1523 arg1 backs 1498:1502 the backs 1494:1502 the backs of BALB/c-nu/nu mice 1494:1523 To examine the effects of AMPK O-GlcNAcylation in vivo, the LoVo cells were s.c. transplanted onto the backs of BALB/c-nu/nu mice. 28973823 2 84 theme N-acetylglucosamine 207:225 arg1 modification 345:356 an essential post-translational modification 313:356 an essential post-translational modification that is upregulated in diabetic patients and has been implicated in tumor growth 313:437 O-linked N-acetylglucosamine (O-GlcNAc) modification of proteins at serine/threonine residues (O-GlcNAcylation) is an essential post-translational modification that is upregulated in diabetic patients and has been implicated in tumor growth. 28973823 2 84 theme N-acetylglucosamine 207:225 arg1 modification 238:249 O-linked N-acetylglucosamine (O-GlcNAc) modification 198:249 O-linked N-acetylglucosamine (O-GlcNAc) modification of proteins at serine/threonine residues (O-GlcNAcylation) 198:308 O-linked N-acetylglucosamine (O-GlcNAc) modification of proteins at serine/threonine residues (O-GlcNAcylation) is an essential post-translational modification that is upregulated in diabetic patients and has been implicated in tumor growth. 28973823 9 85 theme AMPK 1389:1392 arg1 inhibition 1375:1384 both chemical and genetic inhibition 1349:1384 both chemical and genetic inhibition of AMPK 1349:1392 In addition, TMG-mediated acceleration of tumor growth was abolished by both chemical and genetic inhibition of AMPK. 28973823 11 86 theme mice 1613:1616 arg1 tumors 1599:1604 the tumors 1595:1604 the tumors of the mice 1595:1616 Injection of TMG promoted the growth and enhanced O-GlcNAcylation of the tumors of the mice. 28713921 6 0 theme FOXO3‑specific 1226:1239 arg1 phosphorylation 1246:1260 FOXO3‑specific site phosphorylation 1226:1260 FOXO3‑specific site phosphorylation 1226:1260 The present study also examined the phosphoinositide 3‑kinase (PI3K)/AKT and mitogen‑activated protein kinase (MAPK)/ERK pathways, which induce FOXO1‑ and FOXO3‑specific site phosphorylation. 28713921 6 1 dep /AKT 1139:1142 arg1 the 1103:1105 the 1103:1105 the 1103:1105 The present study also examined the phosphoinositide 3‑kinase (PI3K)/AKT and mitogen‑activated protein kinase (MAPK)/ERK pathways, which induce FOXO1‑ and FOXO3‑specific site phosphorylation. 28713921 1 2 theme worldwide 151:159 arg1 cause 114:118 the most common cause 98:118 the most common cause of cancer‑associated mortality worldwide 98:159 Lung cancer is the most common cause of cancer‑associated mortality worldwide, and glucosamine has the potential to exhibit antitumor activity. 28713921 1 2 theme worldwide 151:159 arg1 cancer 88:93 Lung cancer 83:93 Lung cancer 83:93 Lung cancer is the most common cause of cancer‑associated mortality worldwide, and glucosamine has the potential to exhibit antitumor activity. 28713921 8 3 theme cell 1475:1478 arg1 proliferation 1480:1492 A549 cell proliferation 1470:1492 A549 cell proliferation 1470:1492 These observations suggested that glucosamine modulated A549 cell proliferation, possibly via O‑GlcNAc modification‑induced downregulation of the PI3K/AKT and MAPK/ERK pathways and their downstream signaling molecules, FOXO1 and FOXO3. 28713921 0 4 theme FOXO 77:80 arg1 phosphorylation 58:72 the phosphorylation 54:72 the phosphorylation of FOXO 54:80 Anti‑lung cancer effect of glucosamine by suppressing the phosphorylation of FOXO. 28713921 3 5 theme signal‑regulated 635:650 arg1 ERK 660:662 extracellular signal‑regulated kinase (ERK) 621:663 extracellular signal‑regulated kinase (ERK) 621:663 An MTT assay was performed to investigate cell viability and immunoblotting was performed to detect protein levels of FOXO1/3, phosphorylated (p)‑FOXO1/3, AKT, p‑AKT, extracellular signal‑regulated kinase (ERK) and p‑ERK, and the levels of β‑O‑linked N‑acetylglucosamine (O‑GlcNAc)‑modified FOXO1 protein. 28713921 5 6 theme FOXO1‑ 877:882 arg1 phosphorylation 914:928 FOXO1‑ and FOXO3‑specific amino acid phosphorylation 877:928 FOXO1‑ and FOXO3‑specific amino acid phosphorylation 877:928 Glucosamine inhibited FOXO1‑ and FOXO3‑specific amino acid phosphorylation, which was correlated with its translocation from the nucleus to cytoplasm, indicating a possible anti‑lung cancer mechanism of glucosamine. 28713921 3 7 theme extracellular 621:633 arg1 ERK 660:662 extracellular signal‑regulated kinase (ERK) 621:663 extracellular signal‑regulated kinase (ERK) 621:663 An MTT assay was performed to investigate cell viability and immunoblotting was performed to detect protein levels of FOXO1/3, phosphorylated (p)‑FOXO1/3, AKT, p‑AKT, extracellular signal‑regulated kinase (ERK) and p‑ERK, and the levels of β‑O‑linked N‑acetylglucosamine (O‑GlcNAc)‑modified FOXO1 protein. 28713921 3 8 theme kinase 652:657 arg1 ERK 660:662 extracellular signal‑regulated kinase (ERK) 621:663 extracellular signal‑regulated kinase (ERK) 621:663 An MTT assay was performed to investigate cell viability and immunoblotting was performed to detect protein levels of FOXO1/3, phosphorylated (p)‑FOXO1/3, AKT, p‑AKT, extracellular signal‑regulated kinase (ERK) and p‑ERK, and the levels of β‑O‑linked N‑acetylglucosamine (O‑GlcNAc)‑modified FOXO1 protein. 28713921 2 9 from effect 304:309 arg1 activity 349:356 the transcriptional activity 329:356 the transcriptional activity of forkhead box O (FOXO)1 and FOXO3 329:392 To reveal its anti‑lung cancer mechanism, the present study investigated the effect of glucosamine on the transcriptional activity of forkhead box O (FOXO)1 and FOXO3, and associated signal transduction pathways in A549 cells. 28713921 6 10 theme mitogen‑activated 1148:1164 arg1 kinase 1174:1179 mitogen‑activated protein kinase 1148:1179 mitogen‑activated protein kinase (MAPK)/ERK pathways 1148:1199 The present study also examined the phosphoinositide 3‑kinase (PI3K)/AKT and mitogen‑activated protein kinase (MAPK)/ERK pathways, which induce FOXO1‑ and FOXO3‑specific site phosphorylation. 28713921 6 10 theme mitogen‑activated 1148:1164 arg1 MAPK 1182:1185 MAPK 1182:1185 MAPK 1182:1185 The present study also examined the phosphoinositide 3‑kinase (PI3K)/AKT and mitogen‑activated protein kinase (MAPK)/ERK pathways, which induce FOXO1‑ and FOXO3‑specific site phosphorylation. 28713921 8 11 theme pathways 1582:1589 arg1 downregulation 1538:1551 O‑GlcNAc modification‑induced downregulation 1508:1551 O‑GlcNAc modification‑induced downregulation of the PI3K/AKT and MAPK/ERK pathways and their downstream signaling molecules, FOXO1 and FOXO3 1508:1647 These observations suggested that glucosamine modulated A549 cell proliferation, possibly via O‑GlcNAc modification‑induced downregulation of the PI3K/AKT and MAPK/ERK pathways and their downstream signaling molecules, FOXO1 and FOXO3. 28713921 2 12 theme present 273:279 arg1 study 281:285 the present study 269:285 the present study 269:285 To reveal its anti‑lung cancer mechanism, the present study investigated the effect of glucosamine on the transcriptional activity of forkhead box O (FOXO)1 and FOXO3, and associated signal transduction pathways in A549 cells. 28713921 7 13 from cytoplasm 1342:1350 arg1 translocation 1311:1323 the translocation 1307:1323 the translocation of FOXO from the cytoplasm to the nucleus 1307:1365 The data showed that glucosamine suppressed the translocation of FOXO from the cytoplasm to the nucleus via glucosamine‑induced O‑GlcNAc modification. 28713921 6 14 theme phosphoinositide 1107:1122 arg1 3‑kinase 1124:1131 phosphoinositide 3‑kinase 1107:1131 phosphoinositide 3‑kinase (PI3K)/AKT 1107:1142 The present study also examined the phosphoinositide 3‑kinase (PI3K)/AKT and mitogen‑activated protein kinase (MAPK)/ERK pathways, which induce FOXO1‑ and FOXO3‑specific site phosphorylation. 28713921 6 14 theme phosphoinositide 1107:1122 arg1 PI3K 1134:1137 PI3K 1134:1137 PI3K 1134:1137 The present study also examined the phosphoinositide 3‑kinase (PI3K)/AKT and mitogen‑activated protein kinase (MAPK)/ERK pathways, which induce FOXO1‑ and FOXO3‑specific site phosphorylation. 28713921 2 15 from pathways 430:437 arg1 cells 447:451 A549 cells 442:451 A549 cells 442:451 To reveal its anti‑lung cancer mechanism, the present study investigated the effect of glucosamine on the transcriptional activity of forkhead box O (FOXO)1 and FOXO3, and associated signal transduction pathways in A549 cells. 28713921 3 16 dep phosphorylated 581:594 arg1 p 597:597 p 597:597 p 597:597 An MTT assay was performed to investigate cell viability and immunoblotting was performed to detect protein levels of FOXO1/3, phosphorylated (p)‑FOXO1/3, AKT, p‑AKT, extracellular signal‑regulated kinase (ERK) and p‑ERK, and the levels of β‑O‑linked N‑acetylglucosamine (O‑GlcNAc)‑modified FOXO1 protein. 28713921 3 17 theme cell 496:499 arg1 viability 501:509 cell viability 496:509 cell viability 496:509 An MTT assay was performed to investigate cell viability and immunoblotting was performed to detect protein levels of FOXO1/3, phosphorylated (p)‑FOXO1/3, AKT, p‑AKT, extracellular signal‑regulated kinase (ERK) and p‑ERK, and the levels of β‑O‑linked N‑acetylglucosamine (O‑GlcNAc)‑modified FOXO1 protein. 28713921 6 18 theme present 1075:1081 arg1 study 1083:1087 The present study 1071:1087 The present study 1071:1087 The present study also examined the phosphoinositide 3‑kinase (PI3K)/AKT and mitogen‑activated protein kinase (MAPK)/ERK pathways, which induce FOXO1‑ and FOXO3‑specific site phosphorylation. 28713921 6 19 theme 3‑kinase 1124:1131 arg1 /AKT 1139:1142 phosphoinositide 3‑kinase (PI3K)/AKT 1107:1142 phosphoinositide 3‑kinase (PI3K)/AKT 1107:1142 The present study also examined the phosphoinositide 3‑kinase (PI3K)/AKT and mitogen‑activated protein kinase (MAPK)/ERK pathways, which induce FOXO1‑ and FOXO3‑specific site phosphorylation. 28713921 2 20 theme transduction 417:428 arg1 pathways 430:437 signal transduction pathways 410:437 signal transduction pathways in A549 cells 410:451 To reveal its anti‑lung cancer mechanism, the present study investigated the effect of glucosamine on the transcriptional activity of forkhead box O (FOXO)1 and FOXO3, and associated signal transduction pathways in A549 cells. 28713921 3 21 theme MTT 457:459 arg1 assay 461:465 An MTT assay 454:465 An MTT assay 454:465 An MTT assay was performed to investigate cell viability and immunoblotting was performed to detect protein levels of FOXO1/3, phosphorylated (p)‑FOXO1/3, AKT, p‑AKT, extracellular signal‑regulated kinase (ERK) and p‑ERK, and the levels of β‑O‑linked N‑acetylglucosamine (O‑GlcNAc)‑modified FOXO1 protein. 28713921 2 22 theme FOXO 377:380 arg1 activity 349:356 the transcriptional activity 329:356 the transcriptional activity of forkhead box O (FOXO)1 and FOXO3 329:392 To reveal its anti‑lung cancer mechanism, the present study investigated the effect of glucosamine on the transcriptional activity of forkhead box O (FOXO)1 and FOXO3, and associated signal transduction pathways in A549 cells. 28713921 0 23 theme cancer 10:15 arg1 effect 17:22 cancer effect 10:22 cancer effect of glucosamine 10:37 Anti‑lung cancer effect of glucosamine by suppressing the phosphorylation of FOXO. 28713921 8 24 theme molecules 1622:1630 arg1 downregulation 1538:1551 O‑GlcNAc modification‑induced downregulation 1508:1551 O‑GlcNAc modification‑induced downregulation of the PI3K/AKT and MAPK/ERK pathways and their downstream signaling molecules, FOXO1 and FOXO3 1508:1647 These observations suggested that glucosamine modulated A549 cell proliferation, possibly via O‑GlcNAc modification‑induced downregulation of the PI3K/AKT and MAPK/ERK pathways and their downstream signaling molecules, FOXO1 and FOXO3. 28713921 6 25 theme site 1241:1244 arg1 phosphorylation 1246:1260 FOXO3‑specific site phosphorylation 1226:1260 FOXO3‑specific site phosphorylation 1226:1260 The present study also examined the phosphoinositide 3‑kinase (PI3K)/AKT and mitogen‑activated protein kinase (MAPK)/ERK pathways, which induce FOXO1‑ and FOXO3‑specific site phosphorylation. 28713921 1 26 theme Lung 83:86 arg1 cause 114:118 the most common cause 98:118 the most common cause of cancer‑associated mortality worldwide 98:159 Lung cancer is the most common cause of cancer‑associated mortality worldwide, and glucosamine has the potential to exhibit antitumor activity. 28713921 1 26 theme Lung 83:86 arg1 cancer 88:93 Lung cancer 83:93 Lung cancer 83:93 Lung cancer is the most common cause of cancer‑associated mortality worldwide, and glucosamine has the potential to exhibit antitumor activity. 28713921 5 27 from nucleus 984:990 arg1 translocation 961:973 its translocation 957:973 its translocation from the nucleus to cytoplasm 957:1003 Glucosamine inhibited FOXO1‑ and FOXO3‑specific amino acid phosphorylation, which was correlated with its translocation from the nucleus to cytoplasm, indicating a possible anti‑lung cancer mechanism of glucosamine. 28713921 2 28 theme signal 410:415 arg1 pathways 430:437 signal transduction pathways 410:437 signal transduction pathways in A549 cells 410:451 To reveal its anti‑lung cancer mechanism, the present study investigated the effect of glucosamine on the transcriptional activity of forkhead box O (FOXO)1 and FOXO3, and associated signal transduction pathways in A549 cells. 28713921 8 29 theme signaling 1612:1620 arg1 molecules 1622:1630 their downstream signaling molecules 1595:1630 their downstream signaling molecules 1595:1630 These observations suggested that glucosamine modulated A549 cell proliferation, possibly via O‑GlcNAc modification‑induced downregulation of the PI3K/AKT and MAPK/ERK pathways and their downstream signaling molecules, FOXO1 and FOXO3. 28713921 8 29 theme signaling 1612:1620 arg1 FOXO3 1643:1647 FOXO3 1643:1647 FOXO3 1643:1647 These observations suggested that glucosamine modulated A549 cell proliferation, possibly via O‑GlcNAc modification‑induced downregulation of the PI3K/AKT and MAPK/ERK pathways and their downstream signaling molecules, FOXO1 and FOXO3. 28713921 8 29 theme signaling 1612:1620 arg1 FOXO1 1633:1637 FOXO1 1633:1637 FOXO1 1633:1637 These observations suggested that glucosamine modulated A549 cell proliferation, possibly via O‑GlcNAc modification‑induced downregulation of the PI3K/AKT and MAPK/ERK pathways and their downstream signaling molecules, FOXO1 and FOXO3. 28713921 4 30 theme O‑GlcNAc‑modified 804:820 arg1 protein 822:828 O‑GlcNAc‑modified protein 804:828 O‑GlcNAc‑modified protein 804:828 Immunoprecipitation was performed to purify O‑GlcNAc‑modified protein prior to immunoblotting. 28713921 7 31 theme glucosamine‑induced 1371:1389 arg1 modification 1400:1411 glucosamine‑induced O‑GlcNAc modification 1371:1411 glucosamine‑induced O‑GlcNAc modification 1371:1411 The data showed that glucosamine suppressed the translocation of FOXO from the cytoplasm to the nucleus via glucosamine‑induced O‑GlcNAc modification. 28713921 2 32 theme O 374:374 arg1 FOXO 377:380 forkhead box O (FOXO)1 361:382 forkhead box O (FOXO)1 361:382 To reveal its anti‑lung cancer mechanism, the present study investigated the effect of glucosamine on the transcriptional activity of forkhead box O (FOXO)1 and FOXO3, and associated signal transduction pathways in A549 cells. 28713921 6 33 theme /ERK 1187:1190 arg1 pathways 1192:1199 mitogen‑activated protein kinase (MAPK)/ERK pathways 1148:1199 mitogen‑activated protein kinase (MAPK)/ERK pathways 1148:1199 The present study also examined the phosphoinositide 3‑kinase (PI3K)/AKT and mitogen‑activated protein kinase (MAPK)/ERK pathways, which induce FOXO1‑ and FOXO3‑specific site phosphorylation. 28713921 5 34 theme possible 1019:1026 arg1 mechanism 1045:1053 a possible anti‑lung cancer mechanism 1017:1053 a possible anti‑lung cancer mechanism of glucosamine 1017:1068 Glucosamine inhibited FOXO1‑ and FOXO3‑specific amino acid phosphorylation, which was correlated with its translocation from the nucleus to cytoplasm, indicating a possible anti‑lung cancer mechanism of glucosamine. 28713921 8 35 theme MAPK/ERK 1573:1580 arg1 pathways 1582:1589 the PI3K/AKT and MAPK/ERK pathways 1556:1589 pathways 1582:1589 These observations suggested that glucosamine modulated A549 cell proliferation, possibly via O‑GlcNAc modification‑induced downregulation of the PI3K/AKT and MAPK/ERK pathways and their downstream signaling molecules, FOXO1 and FOXO3. 28713921 6 36 theme kinase 1174:1179 arg1 pathways 1192:1199 mitogen‑activated protein kinase (MAPK)/ERK pathways 1148:1199 mitogen‑activated protein kinase (MAPK)/ERK pathways 1148:1199 The present study also examined the phosphoinositide 3‑kinase (PI3K)/AKT and mitogen‑activated protein kinase (MAPK)/ERK pathways, which induce FOXO1‑ and FOXO3‑specific site phosphorylation. 28713921 5 37 theme glucosamine 1058:1068 arg1 mechanism 1045:1053 a possible anti‑lung cancer mechanism 1017:1053 a possible anti‑lung cancer mechanism of glucosamine 1017:1068 Glucosamine inhibited FOXO1‑ and FOXO3‑specific amino acid phosphorylation, which was correlated with its translocation from the nucleus to cytoplasm, indicating a possible anti‑lung cancer mechanism of glucosamine. 28713921 5 38 dep inhibited 867:875 arg1 correlated 941:950 correlated 941:950 was correlated with its translocation from the nucleus to cytoplasm 937:1003 Glucosamine inhibited FOXO1‑ and FOXO3‑specific amino acid phosphorylation, which was correlated with its translocation from the nucleus to cytoplasm, indicating a possible anti‑lung cancer mechanism of glucosamine. 28713921 2 39 theme FOXO3 388:392 arg1 activity 349:356 the transcriptional activity 329:356 the transcriptional activity of forkhead box O (FOXO)1 and FOXO3 329:392 To reveal its anti‑lung cancer mechanism, the present study investigated the effect of glucosamine on the transcriptional activity of forkhead box O (FOXO)1 and FOXO3, and associated signal transduction pathways in A549 cells. 28713921 5 40 theme amino 903:907 arg1 acid 909:912 FOXO3‑specific amino acid 888:912 FOXO3‑specific amino acid 888:912 Glucosamine inhibited FOXO1‑ and FOXO3‑specific amino acid phosphorylation, which was correlated with its translocation from the nucleus to cytoplasm, indicating a possible anti‑lung cancer mechanism of glucosamine. 28713921 1 41 contain has 178:180 arg1 glucosamine 166:176 glucosamine 166:176 glucosamine 166:176 Lung cancer is the most common cause of cancer‑associated mortality worldwide, and glucosamine has the potential to exhibit antitumor activity. 28713921 1 41 contain has 178:180 arg2 potential 186:194 the potential to exhibit antitumor activity 182:224 the potential to exhibit antitumor activity 182:224 Lung cancer is the most common cause of cancer‑associated mortality worldwide, and glucosamine has the potential to exhibit antitumor activity. 28713921 7 42 theme O‑GlcNAc 1391:1398 arg1 modification 1400:1411 glucosamine‑induced O‑GlcNAc modification 1371:1411 glucosamine‑induced O‑GlcNAc modification 1371:1411 The data showed that glucosamine suppressed the translocation of FOXO from the cytoplasm to the nucleus via glucosamine‑induced O‑GlcNAc modification. 28713921 7 43 theme FOXO 1328:1331 arg1 translocation 1311:1323 the translocation 1307:1323 the translocation of FOXO from the cytoplasm to the nucleus 1307:1365 The data showed that glucosamine suppressed the translocation of FOXO from the cytoplasm to the nucleus via glucosamine‑induced O‑GlcNAc modification. 28713921 2 44 theme A549 442:445 arg1 cells 447:451 A549 cells 442:451 A549 cells 442:451 To reveal its anti‑lung cancer mechanism, the present study investigated the effect of glucosamine on the transcriptional activity of forkhead box O (FOXO)1 and FOXO3, and associated signal transduction pathways in A549 cells. 28713921 0 45 theme glucosamine 27:37 arg1 effect 17:22 cancer effect 10:22 cancer effect of glucosamine 10:37 Anti‑lung cancer effect of glucosamine by suppressing the phosphorylation of FOXO. 28713921 3 46 theme FOXO1/3 572:578 arg1 p‑ERK 669:673 p‑ERK 669:673 p‑ERK 669:673 An MTT assay was performed to investigate cell viability and immunoblotting was performed to detect protein levels of FOXO1/3, phosphorylated (p)‑FOXO1/3, AKT, p‑AKT, extracellular signal‑regulated kinase (ERK) and p‑ERK, and the levels of β‑O‑linked N‑acetylglucosamine (O‑GlcNAc)‑modified FOXO1 protein. 28713921 3 46 theme FOXO1/3 572:578 arg1 ‑FOXO1/3 599:606 phosphorylated (p)‑FOXO1/3 581:606 phosphorylated (p)‑FOXO1/3 581:606 An MTT assay was performed to investigate cell viability and immunoblotting was performed to detect protein levels of FOXO1/3, phosphorylated (p)‑FOXO1/3, AKT, p‑AKT, extracellular signal‑regulated kinase (ERK) and p‑ERK, and the levels of β‑O‑linked N‑acetylglucosamine (O‑GlcNAc)‑modified FOXO1 protein. 28713921 3 46 theme FOXO1/3 572:578 arg1 AKT 609:611 AKT 609:611 AKT 609:611 An MTT assay was performed to investigate cell viability and immunoblotting was performed to detect protein levels of FOXO1/3, phosphorylated (p)‑FOXO1/3, AKT, p‑AKT, extracellular signal‑regulated kinase (ERK) and p‑ERK, and the levels of β‑O‑linked N‑acetylglucosamine (O‑GlcNAc)‑modified FOXO1 protein. 28713921 3 46 theme FOXO1/3 572:578 arg1 ERK 660:662 extracellular signal‑regulated kinase (ERK) 621:663 extracellular signal‑regulated kinase (ERK) 621:663 An MTT assay was performed to investigate cell viability and immunoblotting was performed to detect protein levels of FOXO1/3, phosphorylated (p)‑FOXO1/3, AKT, p‑AKT, extracellular signal‑regulated kinase (ERK) and p‑ERK, and the levels of β‑O‑linked N‑acetylglucosamine (O‑GlcNAc)‑modified FOXO1 protein. 28713921 3 46 theme FOXO1/3 572:578 arg1 levels 684:689 the levels 680:689 the levels of β‑O‑linked N‑acetylglucosamine (O‑GlcNAc)‑modified FOXO1 protein 680:757 An MTT assay was performed to investigate cell viability and immunoblotting was performed to detect protein levels of FOXO1/3, phosphorylated (p)‑FOXO1/3, AKT, p‑AKT, extracellular signal‑regulated kinase (ERK) and p‑ERK, and the levels of β‑O‑linked N‑acetylglucosamine (O‑GlcNAc)‑modified FOXO1 protein. 28713921 3 46 theme FOXO1/3 572:578 arg1 p‑AKT 614:618 p‑AKT 614:618 p‑AKT 614:618 An MTT assay was performed to investigate cell viability and immunoblotting was performed to detect protein levels of FOXO1/3, phosphorylated (p)‑FOXO1/3, AKT, p‑AKT, extracellular signal‑regulated kinase (ERK) and p‑ERK, and the levels of β‑O‑linked N‑acetylglucosamine (O‑GlcNAc)‑modified FOXO1 protein. 28713921 3 46 theme FOXO1/3 572:578 arg1 levels 562:567 protein levels 554:567 protein levels of FOXO1/3 554:578 An MTT assay was performed to investigate cell viability and immunoblotting was performed to detect protein levels of FOXO1/3, phosphorylated (p)‑FOXO1/3, AKT, p‑AKT, extracellular signal‑regulated kinase (ERK) and p‑ERK, and the levels of β‑O‑linked N‑acetylglucosamine (O‑GlcNAc)‑modified FOXO1 protein. 28713921 3 47 link β‑O‑linked 694:703 arg1 protein 751:757 β‑O‑linked N‑acetylglucosamine (O‑GlcNAc)‑modified FOXO1 protein 694:757 β‑O‑linked N‑acetylglucosamine (O‑GlcNAc)‑modified FOXO1 protein 694:757 An MTT assay was performed to investigate cell viability and immunoblotting was performed to detect protein levels of FOXO1/3, phosphorylated (p)‑FOXO1/3, AKT, p‑AKT, extracellular signal‑regulated kinase (ERK) and p‑ERK, and the levels of β‑O‑linked N‑acetylglucosamine (O‑GlcNAc)‑modified FOXO1 protein. 28713921 1 48 theme antitumor 207:215 arg1 activity 217:224 antitumor activity 207:224 antitumor activity 207:224 Lung cancer is the most common cause of cancer‑associated mortality worldwide, and glucosamine has the potential to exhibit antitumor activity. 28713921 8 49 theme O‑GlcNAc 1508:1515 arg1 downregulation 1538:1551 O‑GlcNAc modification‑induced downregulation 1508:1551 O‑GlcNAc modification‑induced downregulation of the PI3K/AKT and MAPK/ERK pathways and their downstream signaling molecules, FOXO1 and FOXO3 1508:1647 These observations suggested that glucosamine modulated A549 cell proliferation, possibly via O‑GlcNAc modification‑induced downregulation of the PI3K/AKT and MAPK/ERK pathways and their downstream signaling molecules, FOXO1 and FOXO3. 28713921 3 50 theme O‑GlcNAc 726:733 arg1 protein 751:757 β‑O‑linked N‑acetylglucosamine (O‑GlcNAc)‑modified FOXO1 protein 694:757 β‑O‑linked N‑acetylglucosamine (O‑GlcNAc)‑modified FOXO1 protein 694:757 An MTT assay was performed to investigate cell viability and immunoblotting was performed to detect protein levels of FOXO1/3, phosphorylated (p)‑FOXO1/3, AKT, p‑AKT, extracellular signal‑regulated kinase (ERK) and p‑ERK, and the levels of β‑O‑linked N‑acetylglucosamine (O‑GlcNAc)‑modified FOXO1 protein. 28713921 5 51 theme cancer 1038:1043 arg1 mechanism 1045:1053 a possible anti‑lung cancer mechanism 1017:1053 a possible anti‑lung cancer mechanism of glucosamine 1017:1068 Glucosamine inhibited FOXO1‑ and FOXO3‑specific amino acid phosphorylation, which was correlated with its translocation from the nucleus to cytoplasm, indicating a possible anti‑lung cancer mechanism of glucosamine. 28713921 3 52 theme protein 554:560 arg1 levels 562:567 protein levels 554:567 protein levels of FOXO1/3 554:578 An MTT assay was performed to investigate cell viability and immunoblotting was performed to detect protein levels of FOXO1/3, phosphorylated (p)‑FOXO1/3, AKT, p‑AKT, extracellular signal‑regulated kinase (ERK) and p‑ERK, and the levels of β‑O‑linked N‑acetylglucosamine (O‑GlcNAc)‑modified FOXO1 protein. 28713921 2 53 theme transcriptional 333:347 arg1 activity 349:356 the transcriptional activity 329:356 the transcriptional activity of forkhead box O (FOXO)1 and FOXO3 329:392 To reveal its anti‑lung cancer mechanism, the present study investigated the effect of glucosamine on the transcriptional activity of forkhead box O (FOXO)1 and FOXO3, and associated signal transduction pathways in A549 cells. 28713921 8 54 theme PI3K/AKT 1560:1567 arg1 pathways 1582:1589 the PI3K/AKT and MAPK/ERK pathways 1556:1589 pathways 1582:1589 These observations suggested that glucosamine modulated A549 cell proliferation, possibly via O‑GlcNAc modification‑induced downregulation of the PI3K/AKT and MAPK/ERK pathways and their downstream signaling molecules, FOXO1 and FOXO3. 28713921 3 55 theme β‑O‑linked 694:703 arg1 protein 751:757 β‑O‑linked N‑acetylglucosamine (O‑GlcNAc)‑modified FOXO1 protein 694:757 β‑O‑linked N‑acetylglucosamine (O‑GlcNAc)‑modified FOXO1 protein 694:757 An MTT assay was performed to investigate cell viability and immunoblotting was performed to detect protein levels of FOXO1/3, phosphorylated (p)‑FOXO1/3, AKT, p‑AKT, extracellular signal‑regulated kinase (ERK) and p‑ERK, and the levels of β‑O‑linked N‑acetylglucosamine (O‑GlcNAc)‑modified FOXO1 protein. 28713921 5 56 theme anti‑lung 1028:1036 arg1 mechanism 1045:1053 a possible anti‑lung cancer mechanism 1017:1053 a possible anti‑lung cancer mechanism of glucosamine 1017:1068 Glucosamine inhibited FOXO1‑ and FOXO3‑specific amino acid phosphorylation, which was correlated with its translocation from the nucleus to cytoplasm, indicating a possible anti‑lung cancer mechanism of glucosamine. 28713921 1 57 theme mortality 141:149 arg1 worldwide 151:159 cancer‑associated mortality worldwide 123:159 cancer‑associated mortality worldwide 123:159 Lung cancer is the most common cause of cancer‑associated mortality worldwide, and glucosamine has the potential to exhibit antitumor activity. 28713921 1 58 theme common 107:112 arg1 cause 114:118 the most common cause 98:118 the most common cause of cancer‑associated mortality worldwide 98:159 Lung cancer is the most common cause of cancer‑associated mortality worldwide, and glucosamine has the potential to exhibit antitumor activity. 28713921 1 58 theme common 107:112 arg1 cancer 88:93 Lung cancer 83:93 Lung cancer 83:93 Lung cancer is the most common cause of cancer‑associated mortality worldwide, and glucosamine has the potential to exhibit antitumor activity. 28713921 3 59 theme N‑acetylglucosamine 705:723 arg1 protein 751:757 β‑O‑linked N‑acetylglucosamine (O‑GlcNAc)‑modified FOXO1 protein 694:757 β‑O‑linked N‑acetylglucosamine (O‑GlcNAc)‑modified FOXO1 protein 694:757 An MTT assay was performed to investigate cell viability and immunoblotting was performed to detect protein levels of FOXO1/3, phosphorylated (p)‑FOXO1/3, AKT, p‑AKT, extracellular signal‑regulated kinase (ERK) and p‑ERK, and the levels of β‑O‑linked N‑acetylglucosamine (O‑GlcNAc)‑modified FOXO1 protein. 28713921 1 60 theme cancer‑associated 123:139 arg1 worldwide 151:159 cancer‑associated mortality worldwide 123:159 cancer‑associated mortality worldwide 123:159 Lung cancer is the most common cause of cancer‑associated mortality worldwide, and glucosamine has the potential to exhibit antitumor activity. 28713921 8 61 theme A549 1470:1473 arg1 proliferation 1480:1492 A549 cell proliferation 1470:1492 A549 cell proliferation 1470:1492 These observations suggested that glucosamine modulated A549 cell proliferation, possibly via O‑GlcNAc modification‑induced downregulation of the PI3K/AKT and MAPK/ERK pathways and their downstream signaling molecules, FOXO1 and FOXO3. 28713921 5 62 theme acid 909:912 arg1 phosphorylation 914:928 FOXO1‑ and FOXO3‑specific amino acid phosphorylation 877:928 FOXO1‑ and FOXO3‑specific amino acid phosphorylation 877:928 Glucosamine inhibited FOXO1‑ and FOXO3‑specific amino acid phosphorylation, which was correlated with its translocation from the nucleus to cytoplasm, indicating a possible anti‑lung cancer mechanism of glucosamine. 28713921 3 63 theme FOXO1 745:749 arg1 protein 751:757 β‑O‑linked N‑acetylglucosamine (O‑GlcNAc)‑modified FOXO1 protein 694:757 β‑O‑linked N‑acetylglucosamine (O‑GlcNAc)‑modified FOXO1 protein 694:757 An MTT assay was performed to investigate cell viability and immunoblotting was performed to detect protein levels of FOXO1/3, phosphorylated (p)‑FOXO1/3, AKT, p‑AKT, extracellular signal‑regulated kinase (ERK) and p‑ERK, and the levels of β‑O‑linked N‑acetylglucosamine (O‑GlcNAc)‑modified FOXO1 protein. 28713921 6 64 theme protein 1166:1172 arg1 kinase 1174:1179 mitogen‑activated protein kinase 1148:1179 mitogen‑activated protein kinase (MAPK)/ERK pathways 1148:1199 The present study also examined the phosphoinositide 3‑kinase (PI3K)/AKT and mitogen‑activated protein kinase (MAPK)/ERK pathways, which induce FOXO1‑ and FOXO3‑specific site phosphorylation. 28713921 6 64 theme protein 1166:1172 arg1 MAPK 1182:1185 MAPK 1182:1185 MAPK 1182:1185 The present study also examined the phosphoinositide 3‑kinase (PI3K)/AKT and mitogen‑activated protein kinase (MAPK)/ERK pathways, which induce FOXO1‑ and FOXO3‑specific site phosphorylation. 28713921 5 65 theme FOXO3‑specific 888:901 arg1 acid 909:912 FOXO3‑specific amino acid 888:912 FOXO3‑specific amino acid 888:912 Glucosamine inhibited FOXO1‑ and FOXO3‑specific amino acid phosphorylation, which was correlated with its translocation from the nucleus to cytoplasm, indicating a possible anti‑lung cancer mechanism of glucosamine. 28713921 2 66 theme cancer 251:256 arg1 mechanism 258:266 its anti‑lung cancer mechanism 237:266 its anti‑lung cancer mechanism 237:266 To reveal its anti‑lung cancer mechanism, the present study investigated the effect of glucosamine on the transcriptional activity of forkhead box O (FOXO)1 and FOXO3, and associated signal transduction pathways in A549 cells. 28713921 2 67 theme glucosamine 314:324 arg1 effect 304:309 the effect 300:309 the effect of glucosamine on the transcriptional activity of forkhead box O (FOXO)1 and FOXO3 300:392 To reveal its anti‑lung cancer mechanism, the present study investigated the effect of glucosamine on the transcriptional activity of forkhead box O (FOXO)1 and FOXO3, and associated signal transduction pathways in A549 cells. 28713921 3 68 theme protein 751:757 arg1 p‑ERK 669:673 p‑ERK 669:673 p‑ERK 669:673 An MTT assay was performed to investigate cell viability and immunoblotting was performed to detect protein levels of FOXO1/3, phosphorylated (p)‑FOXO1/3, AKT, p‑AKT, extracellular signal‑regulated kinase (ERK) and p‑ERK, and the levels of β‑O‑linked N‑acetylglucosamine (O‑GlcNAc)‑modified FOXO1 protein. 28713921 3 68 theme protein 751:757 arg1 ‑FOXO1/3 599:606 phosphorylated (p)‑FOXO1/3 581:606 phosphorylated (p)‑FOXO1/3 581:606 An MTT assay was performed to investigate cell viability and immunoblotting was performed to detect protein levels of FOXO1/3, phosphorylated (p)‑FOXO1/3, AKT, p‑AKT, extracellular signal‑regulated kinase (ERK) and p‑ERK, and the levels of β‑O‑linked N‑acetylglucosamine (O‑GlcNAc)‑modified FOXO1 protein. 28713921 3 68 theme protein 751:757 arg1 AKT 609:611 AKT 609:611 AKT 609:611 An MTT assay was performed to investigate cell viability and immunoblotting was performed to detect protein levels of FOXO1/3, phosphorylated (p)‑FOXO1/3, AKT, p‑AKT, extracellular signal‑regulated kinase (ERK) and p‑ERK, and the levels of β‑O‑linked N‑acetylglucosamine (O‑GlcNAc)‑modified FOXO1 protein. 28713921 3 68 theme protein 751:757 arg1 ERK 660:662 extracellular signal‑regulated kinase (ERK) 621:663 extracellular signal‑regulated kinase (ERK) 621:663 An MTT assay was performed to investigate cell viability and immunoblotting was performed to detect protein levels of FOXO1/3, phosphorylated (p)‑FOXO1/3, AKT, p‑AKT, extracellular signal‑regulated kinase (ERK) and p‑ERK, and the levels of β‑O‑linked N‑acetylglucosamine (O‑GlcNAc)‑modified FOXO1 protein. 28713921 3 68 theme protein 751:757 arg1 levels 684:689 the levels 680:689 the levels of β‑O‑linked N‑acetylglucosamine (O‑GlcNAc)‑modified FOXO1 protein 680:757 An MTT assay was performed to investigate cell viability and immunoblotting was performed to detect protein levels of FOXO1/3, phosphorylated (p)‑FOXO1/3, AKT, p‑AKT, extracellular signal‑regulated kinase (ERK) and p‑ERK, and the levels of β‑O‑linked N‑acetylglucosamine (O‑GlcNAc)‑modified FOXO1 protein. 28713921 3 68 theme protein 751:757 arg1 p‑AKT 614:618 p‑AKT 614:618 p‑AKT 614:618 An MTT assay was performed to investigate cell viability and immunoblotting was performed to detect protein levels of FOXO1/3, phosphorylated (p)‑FOXO1/3, AKT, p‑AKT, extracellular signal‑regulated kinase (ERK) and p‑ERK, and the levels of β‑O‑linked N‑acetylglucosamine (O‑GlcNAc)‑modified FOXO1 protein. 28713921 3 68 theme protein 751:757 arg1 levels 562:567 protein levels 554:567 protein levels of FOXO1/3 554:578 An MTT assay was performed to investigate cell viability and immunoblotting was performed to detect protein levels of FOXO1/3, phosphorylated (p)‑FOXO1/3, AKT, p‑AKT, extracellular signal‑regulated kinase (ERK) and p‑ERK, and the levels of β‑O‑linked N‑acetylglucosamine (O‑GlcNAc)‑modified FOXO1 protein. 28713921 8 69 theme modification‑induced 1517:1536 arg1 downregulation 1538:1551 O‑GlcNAc modification‑induced downregulation 1508:1551 O‑GlcNAc modification‑induced downregulation of the PI3K/AKT and MAPK/ERK pathways and their downstream signaling molecules, FOXO1 and FOXO3 1508:1647 These observations suggested that glucosamine modulated A549 cell proliferation, possibly via O‑GlcNAc modification‑induced downregulation of the PI3K/AKT and MAPK/ERK pathways and their downstream signaling molecules, FOXO1 and FOXO3. 28713921 2 70 theme anti‑lung 241:249 arg1 mechanism 258:266 its anti‑lung cancer mechanism 237:266 its anti‑lung cancer mechanism 237:266 To reveal its anti‑lung cancer mechanism, the present study investigated the effect of glucosamine on the transcriptional activity of forkhead box O (FOXO)1 and FOXO3, and associated signal transduction pathways in A549 cells. 28713921 8 71 theme downstream 1601:1610 arg1 molecules 1622:1630 their downstream signaling molecules 1595:1630 their downstream signaling molecules 1595:1630 These observations suggested that glucosamine modulated A549 cell proliferation, possibly via O‑GlcNAc modification‑induced downregulation of the PI3K/AKT and MAPK/ERK pathways and their downstream signaling molecules, FOXO1 and FOXO3. 28713921 8 71 theme downstream 1601:1610 arg1 FOXO3 1643:1647 FOXO3 1643:1647 FOXO3 1643:1647 These observations suggested that glucosamine modulated A549 cell proliferation, possibly via O‑GlcNAc modification‑induced downregulation of the PI3K/AKT and MAPK/ERK pathways and their downstream signaling molecules, FOXO1 and FOXO3. 28713921 8 71 theme downstream 1601:1610 arg1 FOXO1 1633:1637 FOXO1 1633:1637 FOXO1 1633:1637 These observations suggested that glucosamine modulated A549 cell proliferation, possibly via O‑GlcNAc modification‑induced downregulation of the PI3K/AKT and MAPK/ERK pathways and their downstream signaling molecules, FOXO1 and FOXO3. 28713921 2 72 theme box 370:372 arg1 FOXO 377:380 forkhead box O (FOXO)1 361:382 forkhead box O (FOXO)1 361:382 To reveal its anti‑lung cancer mechanism, the present study investigated the effect of glucosamine on the transcriptional activity of forkhead box O (FOXO)1 and FOXO3, and associated signal transduction pathways in A549 cells. 28713921 3 73 theme phosphorylated 581:594 arg1 ‑FOXO1/3 599:606 phosphorylated (p)‑FOXO1/3 581:606 phosphorylated (p)‑FOXO1/3 581:606 An MTT assay was performed to investigate cell viability and immunoblotting was performed to detect protein levels of FOXO1/3, phosphorylated (p)‑FOXO1/3, AKT, p‑AKT, extracellular signal‑regulated kinase (ERK) and p‑ERK, and the levels of β‑O‑linked N‑acetylglucosamine (O‑GlcNAc)‑modified FOXO1 protein. 28713921 2 74 theme forkhead 361:368 arg1 FOXO 377:380 forkhead box O (FOXO)1 361:382 forkhead box O (FOXO)1 361:382 To reveal its anti‑lung cancer mechanism, the present study investigated the effect of glucosamine on the transcriptional activity of forkhead box O (FOXO)1 and FOXO3, and associated signal transduction pathways in A549 cells. 28713921 3 75 theme ‑modified 735:743 arg1 protein 751:757 β‑O‑linked N‑acetylglucosamine (O‑GlcNAc)‑modified FOXO1 protein 694:757 β‑O‑linked N‑acetylglucosamine (O‑GlcNAc)‑modified FOXO1 protein 694:757 An MTT assay was performed to investigate cell viability and immunoblotting was performed to detect protein levels of FOXO1/3, phosphorylated (p)‑FOXO1/3, AKT, p‑AKT, extracellular signal‑regulated kinase (ERK) and p‑ERK, and the levels of β‑O‑linked N‑acetylglucosamine (O‑GlcNAc)‑modified FOXO1 protein. 27888523 1 0 gly glycosylated 180:191 arg1 proteins 153:160 Arabinogalactan proteins 137:160 Arabinogalactan proteins (AGPs) 137:167 Arabinogalactan proteins (AGPs) are highly glycosylated proteins that play pivotal roles in diverse developmental processes in plants. 27888523 1 0 gly glycosylated 180:191 arg1 proteins 193:200 highly glycosylated proteins 173:200 highly glycosylated proteins that play pivotal roles in diverse developmental processes in plants 173:269 Arabinogalactan proteins (AGPs) are highly glycosylated proteins that play pivotal roles in diverse developmental processes in plants. 27888523 10 1 theme other 1633:1637 arg1 members 1658:1664 other cotton GT31 family members 1633:1664 other cotton GT31 family members 1633:1664 We also show that GhGalT1 can form homo- and heterodimers with other cotton GT31 family members to facilitate AG glycan assembly of AGPs. 27888523 4 2 from role 659:662 arg1 development 744:754 cotton fiber development 731:754 cotton fiber development 731:754 Here, we characterized the role of a CAZy glycosyltransferase 31 (GT31) family member, GhGalT1, in cotton fiber development. 27888523 2 3 theme O-linked 299:306 arg1 glycans 283:289 Type-II AG glycans 272:289 Type-II AG glycans 272:289 Type-II AG glycans, mostly O-linked to the hydroxyproline residues of the protein backbone, account for up to 95% w/w of the AGP, but their functions are still largely unclear. 27888523 7 4 theme galactose 1061:1069 arg1 ratio 1082:1086 The galactose: arabinose ratio 1057:1086 The galactose: arabinose ratio of AG glycans 1057:1100 The galactose: arabinose ratio of AG glycans was higher in GhGalT1 overexpression fibers, but was lower in GhGalT1-silenced lines, compared with that in the wild type. 27888523 7 4 theme galactose 1061:1069 arg1 higher 1106:1111 higher 1106:1111 higher 1106:1111 The galactose: arabinose ratio of AG glycans was higher in GhGalT1 overexpression fibers, but was lower in GhGalT1-silenced lines, compared with that in the wild type. 27888523 7 4 theme galactose 1061:1069 arg1 lower 1155:1159 lower 1155:1159 lower 1155:1159 The galactose: arabinose ratio of AG glycans was higher in GhGalT1 overexpression fibers, but was lower in GhGalT1-silenced lines, compared with that in the wild type. 27888523 1 5 theme diverse 229:235 arg1 processes 251:259 diverse developmental processes 229:259 diverse developmental processes in plants 229:269 Arabinogalactan proteins (AGPs) are highly glycosylated proteins that play pivotal roles in diverse developmental processes in plants. 27888523 10 6 theme glycan 1683:1688 arg1 assembly 1690:1697 AG glycan assembly 1680:1697 AG glycan assembly of AGPs 1680:1705 We also show that GhGalT1 can form homo- and heterodimers with other cotton GT31 family members to facilitate AG glycan assembly of AGPs. 27888523 5 7 theme transgenic 781:790 arg1 GhGalT1 814:820 the transgenic cotton overexpressing GhGalT1 777:820 the transgenic cotton overexpressing GhGalT1 777:820 The fiber length of the transgenic cotton overexpressing GhGalT1 was shorter than that of the wild type, whereas in the GhGalT1-silenced lines there was a notable increase in fiber length compared with wild type. 27888523 8 8 theme FLA 1361:1363 arg1 genes 1375:1379 the fasciclin-like AGP (FLA) backbone genes 1337:1379 the fasciclin-like AGP (FLA) backbone genes 1337:1379 Overexpression of GhGalT1 upregulates transcript levels of a broad range of cell wall-related genes, especially the fasciclin-like AGP (FLA) backbone genes. 27888523 8 8 theme FLA 1361:1363 arg1 genes 1319:1323 cell wall-related genes 1301:1323 cell wall-related genes 1301:1323 Overexpression of GhGalT1 upregulates transcript levels of a broad range of cell wall-related genes, especially the fasciclin-like AGP (FLA) backbone genes. 27888523 9 9 theme activity 1392:1399 arg1 assay 1401:1405 An enzyme activity assay 1382:1405 An enzyme activity assay 1382:1405 An enzyme activity assay demonstrated that GhGalT1 is a β-1,3-galactosyltransferase (β-1,3-GalT) involved in biosynthesis of the β-1,3-galactan backbone of the type-II AG glycans of AGPs. 27888523 8 10 theme backbone 1366:1373 arg1 genes 1375:1379 the fasciclin-like AGP (FLA) backbone genes 1337:1379 the fasciclin-like AGP (FLA) backbone genes 1337:1379 Overexpression of GhGalT1 upregulates transcript levels of a broad range of cell wall-related genes, especially the fasciclin-like AGP (FLA) backbone genes. 27888523 8 10 theme backbone 1366:1373 arg1 genes 1319:1323 cell wall-related genes 1301:1323 cell wall-related genes 1301:1323 Overexpression of GhGalT1 upregulates transcript levels of a broad range of cell wall-related genes, especially the fasciclin-like AGP (FLA) backbone genes. 27888523 6 11 theme transgenic 1038:1047 arg1 cotton 1049:1054 GhGalT1 transgenic cotton 1030:1054 GhGalT1 transgenic cotton 1030:1054 The carbohydrate moieties of AGPs were altered in fibers of GhGalT1 transgenic cotton. 27888523 4 12 theme glycosyltransferase 674:692 arg1 GhGalT1 719:725 GhGalT1 719:725 GhGalT1 719:725 Here, we characterized the role of a CAZy glycosyltransferase 31 (GT31) family member, GhGalT1, in cotton fiber development. 27888523 4 12 theme glycosyltransferase 674:692 arg1 member 711:716 a CAZy glycosyltransferase 31 (GT31) family member 667:716 a CAZy glycosyltransferase 31 (GT31) family member 667:716 Here, we characterized the role of a CAZy glycosyltransferase 31 (GT31) family member, GhGalT1, in cotton fiber development. 27888523 1 13 theme Arabinogalactan 137:151 arg1 proteins 153:160 Arabinogalactan proteins 137:160 Arabinogalactan proteins (AGPs) 137:167 Arabinogalactan proteins (AGPs) are highly glycosylated proteins that play pivotal roles in diverse developmental processes in plants. 27888523 1 13 theme Arabinogalactan 137:151 arg1 proteins 193:200 highly glycosylated proteins 173:200 highly glycosylated proteins that play pivotal roles in diverse developmental processes in plants 173:269 Arabinogalactan proteins (AGPs) are highly glycosylated proteins that play pivotal roles in diverse developmental processes in plants. 27888523 1 13 theme Arabinogalactan 137:151 arg1 AGPs 163:166 AGPs 163:166 AGPs 163:166 Arabinogalactan proteins (AGPs) are highly glycosylated proteins that play pivotal roles in diverse developmental processes in plants. 27888523 8 14 theme cell 1301:1304 arg1 genes 1375:1379 the fasciclin-like AGP (FLA) backbone genes 1337:1379 the fasciclin-like AGP (FLA) backbone genes 1337:1379 Overexpression of GhGalT1 upregulates transcript levels of a broad range of cell wall-related genes, especially the fasciclin-like AGP (FLA) backbone genes. 27888523 8 14 theme cell 1301:1304 arg1 genes 1319:1323 cell wall-related genes 1301:1323 cell wall-related genes 1301:1323 Overexpression of GhGalT1 upregulates transcript levels of a broad range of cell wall-related genes, especially the fasciclin-like AGP (FLA) backbone genes. 27888523 1 15 from processes 251:259 arg1 plants 264:269 plants 264:269 plants 264:269 Arabinogalactan proteins (AGPs) are highly glycosylated proteins that play pivotal roles in diverse developmental processes in plants. 27888523 2 16 theme AG 280:281 arg1 glycans 283:289 Type-II AG glycans 272:289 Type-II AG glycans 272:289 Type-II AG glycans, mostly O-linked to the hydroxyproline residues of the protein backbone, account for up to 95% w/w of the AGP, but their functions are still largely unclear. 27888523 5 17 theme wild 851:854 arg1 type 856:859 the wild type 847:859 the wild type 847:859 The fiber length of the transgenic cotton overexpressing GhGalT1 was shorter than that of the wild type, whereas in the GhGalT1-silenced lines there was a notable increase in fiber length compared with wild type. 27888523 7 18 theme GhGalT1 1116:1122 arg1 fibers 1139:1144 GhGalT1 overexpression fibers 1116:1144 GhGalT1 overexpression fibers 1116:1144 The galactose: arabinose ratio of AG glycans was higher in GhGalT1 overexpression fibers, but was lower in GhGalT1-silenced lines, compared with that in the wild type. 27888523 8 19 theme range 1292:1296 arg1 levels 1274:1279 transcript levels 1263:1279 transcript levels of a broad range of cell wall-related genes, especially the fasciclin-like AGP (FLA) backbone genes 1263:1379 Overexpression of GhGalT1 upregulates transcript levels of a broad range of cell wall-related genes, especially the fasciclin-like AGP (FLA) backbone genes. 27888523 5 20 theme fiber 761:765 arg1 shorter 826:832 shorter 826:832 shorter 826:832 The fiber length of the transgenic cotton overexpressing GhGalT1 was shorter than that of the wild type, whereas in the GhGalT1-silenced lines there was a notable increase in fiber length compared with wild type. 27888523 5 20 theme fiber 761:765 arg1 length 767:772 The fiber length 757:772 The fiber length of the transgenic cotton overexpressing GhGalT1 757:820 The fiber length of the transgenic cotton overexpressing GhGalT1 was shorter than that of the wild type, whereas in the GhGalT1-silenced lines there was a notable increase in fiber length compared with wild type. 27888523 5 21 theme GhGalT1-silenced 877:892 arg1 lines 894:898 the GhGalT1-silenced lines 873:898 the GhGalT1-silenced lines 873:898 The fiber length of the transgenic cotton overexpressing GhGalT1 was shorter than that of the wild type, whereas in the GhGalT1-silenced lines there was a notable increase in fiber length compared with wild type. 27888523 6 22 theme AGPs 999:1002 arg1 moieties 987:994 The carbohydrate moieties 970:994 The carbohydrate moieties of AGPs 970:1002 The carbohydrate moieties of AGPs were altered in fibers of GhGalT1 transgenic cotton. 27888523 4 23 theme member 711:716 arg1 role 659:662 the role 655:662 the role of a CAZy glycosyltransferase 31 (GT31) family member, GhGalT1, in cotton fiber development 655:754 Here, we characterized the role of a CAZy glycosyltransferase 31 (GT31) family member, GhGalT1, in cotton fiber development. 27888523 7 24 theme glycans 1094:1100 arg1 ratio 1082:1086 The galactose: arabinose ratio 1057:1086 The galactose: arabinose ratio of AG glycans 1057:1100 The galactose: arabinose ratio of AG glycans was higher in GhGalT1 overexpression fibers, but was lower in GhGalT1-silenced lines, compared with that in the wild type. 27888523 7 24 theme glycans 1094:1100 arg1 higher 1106:1111 higher 1106:1111 higher 1106:1111 The galactose: arabinose ratio of AG glycans was higher in GhGalT1 overexpression fibers, but was lower in GhGalT1-silenced lines, compared with that in the wild type. 27888523 7 24 theme glycans 1094:1100 arg1 lower 1155:1159 lower 1155:1159 lower 1155:1159 The galactose: arabinose ratio of AG glycans was higher in GhGalT1 overexpression fibers, but was lower in GhGalT1-silenced lines, compared with that in the wild type. 27888523 9 25 theme β-1,3-galactan 1511:1524 arg1 backbone 1526:1533 the β-1,3-galactan backbone 1507:1533 the β-1,3-galactan backbone of the type-II AG glycans of AGPs 1507:1567 An enzyme activity assay demonstrated that GhGalT1 is a β-1,3-galactosyltransferase (β-1,3-GalT) involved in biosynthesis of the β-1,3-galactan backbone of the type-II AG glycans of AGPs. 27888523 8 26 theme genes 1319:1323 arg1 range 1292:1296 a broad range 1284:1296 a broad range of cell wall-related genes, especially the fasciclin-like AGP (FLA) backbone genes 1284:1379 Overexpression of GhGalT1 upregulates transcript levels of a broad range of cell wall-related genes, especially the fasciclin-like AGP (FLA) backbone genes. 27888523 2 27 theme AGP 397:399 arg1 AGP 397:399 the AGP 393:399 the AGP 393:399 Type-II AG glycans, mostly O-linked to the hydroxyproline residues of the protein backbone, account for up to 95% w/w of the AGP, but their functions are still largely unclear. 27888523 2 27 theme AGP 397:399 arg1 % 384:384 up to 95% 376:384 up to 95% w/w of the AGP 376:399 Type-II AG glycans, mostly O-linked to the hydroxyproline residues of the protein backbone, account for up to 95% w/w of the AGP, but their functions are still largely unclear. 27888523 5 28 theme GhGalT1 814:820 arg1 shorter 826:832 shorter 826:832 shorter 826:832 The fiber length of the transgenic cotton overexpressing GhGalT1 was shorter than that of the wild type, whereas in the GhGalT1-silenced lines there was a notable increase in fiber length compared with wild type. 27888523 5 28 theme GhGalT1 814:820 arg1 length 767:772 The fiber length 757:772 The fiber length of the transgenic cotton overexpressing GhGalT1 757:820 The fiber length of the transgenic cotton overexpressing GhGalT1 was shorter than that of the wild type, whereas in the GhGalT1-silenced lines there was a notable increase in fiber length compared with wild type. 27888523 5 29 theme wild 959:962 arg1 type 964:967 wild type 959:967 wild type 959:967 The fiber length of the transgenic cotton overexpressing GhGalT1 was shorter than that of the wild type, whereas in the GhGalT1-silenced lines there was a notable increase in fiber length compared with wild type. 27888523 7 30 theme wild 1214:1217 arg1 type 1219:1222 the wild type 1210:1222 the wild type 1210:1222 The galactose: arabinose ratio of AG glycans was higher in GhGalT1 overexpression fibers, but was lower in GhGalT1-silenced lines, compared with that in the wild type. 27888523 3 31 theme cell 614:617 arg1 development 619:629 fiber cell development 608:629 fiber cell development 608:629 Cotton fibers are extremely elongated single-cell trichomes on the seed epidermis; however, little is known of the molecular basis governing the regulation of fiber cell development. 27888523 11 32 theme fiber 1766:1770 arg1 development 1772:1782 cotton fiber development 1759:1782 cotton fiber development 1759:1782 Thus, our data demonstrate that GhGalT1 influences cotton fiber development via controlling the glycosylation of AGPs, especially FLAs. 27888523 7 33 theme arabinose 1072:1080 arg1 ratio 1082:1086 The galactose: arabinose ratio 1057:1086 The galactose: arabinose ratio of AG glycans 1057:1100 The galactose: arabinose ratio of AG glycans was higher in GhGalT1 overexpression fibers, but was lower in GhGalT1-silenced lines, compared with that in the wild type. 27888523 7 33 theme arabinose 1072:1080 arg1 higher 1106:1111 higher 1106:1111 higher 1106:1111 The galactose: arabinose ratio of AG glycans was higher in GhGalT1 overexpression fibers, but was lower in GhGalT1-silenced lines, compared with that in the wild type. 27888523 7 33 theme arabinose 1072:1080 arg1 lower 1155:1159 lower 1155:1159 lower 1155:1159 The galactose: arabinose ratio of AG glycans was higher in GhGalT1 overexpression fibers, but was lower in GhGalT1-silenced lines, compared with that in the wild type. 27888523 9 34 theme type-II 1542:1548 arg1 glycans 1553:1559 the type-II AG glycans 1538:1559 the type-II AG glycans of AGPs 1538:1567 An enzyme activity assay demonstrated that GhGalT1 is a β-1,3-galactosyltransferase (β-1,3-GalT) involved in biosynthesis of the β-1,3-galactan backbone of the type-II AG glycans of AGPs. 27888523 8 35 theme fasciclin-like 1341:1354 arg1 genes 1375:1379 the fasciclin-like AGP (FLA) backbone genes 1337:1379 the fasciclin-like AGP (FLA) backbone genes 1337:1379 Overexpression of GhGalT1 upregulates transcript levels of a broad range of cell wall-related genes, especially the fasciclin-like AGP (FLA) backbone genes. 27888523 8 35 theme fasciclin-like 1341:1354 arg1 genes 1319:1323 cell wall-related genes 1301:1323 cell wall-related genes 1301:1323 Overexpression of GhGalT1 upregulates transcript levels of a broad range of cell wall-related genes, especially the fasciclin-like AGP (FLA) backbone genes. 27888523 2 36 theme protein 346:352 arg1 backbone 354:361 the protein backbone 342:361 the protein backbone 342:361 Type-II AG glycans, mostly O-linked to the hydroxyproline residues of the protein backbone, account for up to 95% w/w of the AGP, but their functions are still largely unclear. 27888523 1 37 theme developmental 237:249 arg1 processes 251:259 diverse developmental processes 229:259 diverse developmental processes in plants 229:269 Arabinogalactan proteins (AGPs) are highly glycosylated proteins that play pivotal roles in diverse developmental processes in plants. 27888523 9 38 theme glycans 1553:1559 arg1 backbone 1526:1533 the β-1,3-galactan backbone 1507:1533 the β-1,3-galactan backbone of the type-II AG glycans of AGPs 1507:1567 An enzyme activity assay demonstrated that GhGalT1 is a β-1,3-galactosyltransferase (β-1,3-GalT) involved in biosynthesis of the β-1,3-galactan backbone of the type-II AG glycans of AGPs. 27888523 6 39 theme cotton 1049:1054 arg1 fibers 1020:1025 fibers 1020:1025 fibers of GhGalT1 transgenic cotton 1020:1054 The carbohydrate moieties of AGPs were altered in fibers of GhGalT1 transgenic cotton. 27888523 10 40 theme family 1651:1656 arg1 members 1658:1664 other cotton GT31 family members 1633:1664 other cotton GT31 family members 1633:1664 We also show that GhGalT1 can form homo- and heterodimers with other cotton GT31 family members to facilitate AG glycan assembly of AGPs. 27888523 9 41 theme AGPs 1564:1567 arg1 glycans 1553:1559 the type-II AG glycans 1538:1559 the type-II AG glycans of AGPs 1538:1567 An enzyme activity assay demonstrated that GhGalT1 is a β-1,3-galactosyltransferase (β-1,3-GalT) involved in biosynthesis of the β-1,3-galactan backbone of the type-II AG glycans of AGPs. 27888523 6 42 theme GhGalT1 1030:1036 arg1 cotton 1049:1054 GhGalT1 transgenic cotton 1030:1054 GhGalT1 transgenic cotton 1030:1054 The carbohydrate moieties of AGPs were altered in fibers of GhGalT1 transgenic cotton. 27888523 2 43 dep % 384:384 arg1 w/w 386:388 w/w 386:388 up to 95% w/w of the AGP 376:399 Type-II AG glycans, mostly O-linked to the hydroxyproline residues of the protein backbone, account for up to 95% w/w of the AGP, but their functions are still largely unclear. 27888523 3 44 theme single-cell 487:497 arg1 trichomes 499:507 extremely elongated single-cell trichomes 467:507 extremely elongated single-cell trichomes on the seed epidermis 467:529 Cotton fibers are extremely elongated single-cell trichomes on the seed epidermis; however, little is known of the molecular basis governing the regulation of fiber cell development. 27888523 3 44 theme single-cell 487:497 arg1 fibers 456:461 Cotton fibers 449:461 Cotton fibers 449:461 Cotton fibers are extremely elongated single-cell trichomes on the seed epidermis; however, little is known of the molecular basis governing the regulation of fiber cell development. 27888523 5 45 from increase 920:927 arg1 length 938:943 fiber length 932:943 fiber length 932:943 The fiber length of the transgenic cotton overexpressing GhGalT1 was shorter than that of the wild type, whereas in the GhGalT1-silenced lines there was a notable increase in fiber length compared with wild type. 27888523 7 46 theme GhGalT1-silenced 1164:1179 arg1 lines 1181:1185 GhGalT1-silenced lines 1164:1185 GhGalT1-silenced lines 1164:1185 The galactose: arabinose ratio of AG glycans was higher in GhGalT1 overexpression fibers, but was lower in GhGalT1-silenced lines, compared with that in the wild type. 27888523 3 47 from trichomes 499:507 arg1 epidermis 521:529 the seed epidermis 512:529 the seed epidermis 512:529 Cotton fibers are extremely elongated single-cell trichomes on the seed epidermis; however, little is known of the molecular basis governing the regulation of fiber cell development. 27888523 10 48 theme AG 1680:1681 arg1 assembly 1690:1697 AG glycan assembly 1680:1697 AG glycan assembly of AGPs 1680:1705 We also show that GhGalT1 can form homo- and heterodimers with other cotton GT31 family members to facilitate AG glycan assembly of AGPs. 27888523 5 49 theme fiber 932:936 arg1 length 938:943 fiber length 932:943 fiber length 932:943 The fiber length of the transgenic cotton overexpressing GhGalT1 was shorter than that of the wild type, whereas in the GhGalT1-silenced lines there was a notable increase in fiber length compared with wild type. 27888523 3 50 theme seed 516:519 arg1 epidermis 521:529 the seed epidermis 512:529 the seed epidermis 512:529 Cotton fibers are extremely elongated single-cell trichomes on the seed epidermis; however, little is known of the molecular basis governing the regulation of fiber cell development. 27888523 1 51 theme glycosylated 180:191 arg1 proteins 153:160 Arabinogalactan proteins 137:160 Arabinogalactan proteins (AGPs) 137:167 Arabinogalactan proteins (AGPs) are highly glycosylated proteins that play pivotal roles in diverse developmental processes in plants. 27888523 1 51 theme glycosylated 180:191 arg1 proteins 193:200 highly glycosylated proteins 173:200 highly glycosylated proteins that play pivotal roles in diverse developmental processes in plants 173:269 Arabinogalactan proteins (AGPs) are highly glycosylated proteins that play pivotal roles in diverse developmental processes in plants. 27888523 10 52 theme AGPs 1702:1705 arg1 assembly 1690:1697 AG glycan assembly 1680:1697 AG glycan assembly of AGPs 1680:1705 We also show that GhGalT1 can form homo- and heterodimers with other cotton GT31 family members to facilitate AG glycan assembly of AGPs. 27888523 2 53 theme hydroxyproline 315:328 arg1 backbone 354:361 the protein backbone 342:361 the protein backbone 342:361 Type-II AG glycans, mostly O-linked to the hydroxyproline residues of the protein backbone, account for up to 95% w/w of the AGP, but their functions are still largely unclear. 27888523 2 53 theme hydroxyproline 315:328 arg1 residues 330:337 the hydroxyproline residues 311:337 the hydroxyproline residues of the protein backbone 311:361 Type-II AG glycans, mostly O-linked to the hydroxyproline residues of the protein backbone, account for up to 95% w/w of the AGP, but their functions are still largely unclear. 27888523 1 54 theme pivotal 212:218 arg1 roles 220:224 pivotal roles 212:224 pivotal roles 212:224 Arabinogalactan proteins (AGPs) are highly glycosylated proteins that play pivotal roles in diverse developmental processes in plants. 27888523 11 55 gly glycosylation 1804:1816 arg1 AGPs 1821:1824 AGPs 1821:1824 AGPs 1821:1824 Thus, our data demonstrate that GhGalT1 influences cotton fiber development via controlling the glycosylation of AGPs, especially FLAs. 27888523 11 55 gly glycosylation 1804:1816 arg1 FLAs 1838:1841 FLAs 1838:1841 FLAs 1838:1841 Thus, our data demonstrate that GhGalT1 influences cotton fiber development via controlling the glycosylation of AGPs, especially FLAs. 27888523 2 56 link O-linked 299:306 arg1 glycans 283:289 Type-II AG glycans 272:289 Type-II AG glycans 272:289 Type-II AG glycans, mostly O-linked to the hydroxyproline residues of the protein backbone, account for up to 95% w/w of the AGP, but their functions are still largely unclear. 27888523 3 57 theme molecular 564:572 arg1 basis 574:578 the molecular basis 560:578 the molecular basis governing the regulation of fiber cell development 560:629 Cotton fibers are extremely elongated single-cell trichomes on the seed epidermis; however, little is known of the molecular basis governing the regulation of fiber cell development. 27888523 5 58 theme cotton 792:797 arg1 GhGalT1 814:820 the transgenic cotton overexpressing GhGalT1 777:820 the transgenic cotton overexpressing GhGalT1 777:820 The fiber length of the transgenic cotton overexpressing GhGalT1 was shorter than that of the wild type, whereas in the GhGalT1-silenced lines there was a notable increase in fiber length compared with wild type. 27888523 4 59 theme CAZy 669:672 arg1 GhGalT1 719:725 GhGalT1 719:725 GhGalT1 719:725 Here, we characterized the role of a CAZy glycosyltransferase 31 (GT31) family member, GhGalT1, in cotton fiber development. 27888523 4 59 theme CAZy 669:672 arg1 member 711:716 a CAZy glycosyltransferase 31 (GT31) family member 667:716 a CAZy glycosyltransferase 31 (GT31) family member 667:716 Here, we characterized the role of a CAZy glycosyltransferase 31 (GT31) family member, GhGalT1, in cotton fiber development. 27888523 4 60 theme fiber 738:742 arg1 development 744:754 cotton fiber development 731:754 cotton fiber development 731:754 Here, we characterized the role of a CAZy glycosyltransferase 31 (GT31) family member, GhGalT1, in cotton fiber development. 27888523 0 61 theme arabinogalactan 65:79 arg1 proteins 81:88 arabinogalactan proteins 65:88 arabinogalactan proteins 65:88 The cotton β-galactosyltransferase 1 (GalT1) that galactosylates arabinogalactan proteins participates in controlling fiber development. 27888523 2 62 theme backbone 354:361 arg1 backbone 354:361 the protein backbone 342:361 the protein backbone 342:361 Type-II AG glycans, mostly O-linked to the hydroxyproline residues of the protein backbone, account for up to 95% w/w of the AGP, but their functions are still largely unclear. 27888523 2 62 theme backbone 354:361 arg1 residues 330:337 the hydroxyproline residues 311:337 the hydroxyproline residues of the protein backbone 311:361 Type-II AG glycans, mostly O-linked to the hydroxyproline residues of the protein backbone, account for up to 95% w/w of the AGP, but their functions are still largely unclear. 27888523 2 63 theme Type-II 272:278 arg1 glycans 283:289 Type-II AG glycans 272:289 Type-II AG glycans 272:289 Type-II AG glycans, mostly O-linked to the hydroxyproline residues of the protein backbone, account for up to 95% w/w of the AGP, but their functions are still largely unclear. 27888523 8 64 theme GhGalT1 1243:1249 arg1 Overexpression 1225:1238 Overexpression 1225:1238 Overexpression of GhGalT1 1225:1249 Overexpression of GhGalT1 upregulates transcript levels of a broad range of cell wall-related genes, especially the fasciclin-like AGP (FLA) backbone genes. 27888523 7 65 theme overexpression 1124:1137 arg1 fibers 1139:1144 GhGalT1 overexpression fibers 1116:1144 GhGalT1 overexpression fibers 1116:1144 The galactose: arabinose ratio of AG glycans was higher in GhGalT1 overexpression fibers, but was lower in GhGalT1-silenced lines, compared with that in the wild type. 27888523 2 66 dep 95 382:383 arg1 to 379:380 to 379:380 to 379:380 Type-II AG glycans, mostly O-linked to the hydroxyproline residues of the protein backbone, account for up to 95% w/w of the AGP, but their functions are still largely unclear. 27888523 8 67 theme transcript 1263:1272 arg1 levels 1274:1279 transcript levels 1263:1279 transcript levels of a broad range of cell wall-related genes, especially the fasciclin-like AGP (FLA) backbone genes 1263:1379 Overexpression of GhGalT1 upregulates transcript levels of a broad range of cell wall-related genes, especially the fasciclin-like AGP (FLA) backbone genes. 27888523 5 68 theme notable 912:918 arg1 increase 920:927 a notable increase 910:927 a notable increase in fiber length 910:943 The fiber length of the transgenic cotton overexpressing GhGalT1 was shorter than that of the wild type, whereas in the GhGalT1-silenced lines there was a notable increase in fiber length compared with wild type. 27888523 0 69 theme cotton 4:9 arg1 β-galactosyltransferase 11:33 The cotton β-galactosyltransferase 1 0:35 The cotton β-galactosyltransferase 1 (GalT1) that galactosylates arabinogalactan proteins 0:88 The cotton β-galactosyltransferase 1 (GalT1) that galactosylates arabinogalactan proteins participates in controlling fiber development. 27888523 0 69 theme cotton 4:9 arg1 GalT1 38:42 GalT1 38:42 GalT1 38:42 The cotton β-galactosyltransferase 1 (GalT1) that galactosylates arabinogalactan proteins participates in controlling fiber development. 27888523 8 70 theme broad 1286:1290 arg1 range 1292:1296 a broad range 1284:1296 a broad range of cell wall-related genes, especially the fasciclin-like AGP (FLA) backbone genes 1284:1379 Overexpression of GhGalT1 upregulates transcript levels of a broad range of cell wall-related genes, especially the fasciclin-like AGP (FLA) backbone genes. 27888523 11 71 theme AGPs 1821:1824 arg1 glycosylation 1804:1816 the glycosylation 1800:1816 the glycosylation of AGPs, especially FLAs 1800:1841 Thus, our data demonstrate that GhGalT1 influences cotton fiber development via controlling the glycosylation of AGPs, especially FLAs. 27888523 7 72 theme AG 1091:1092 arg1 glycans 1094:1100 AG glycans 1091:1100 AG glycans 1091:1100 The galactose: arabinose ratio of AG glycans was higher in GhGalT1 overexpression fibers, but was lower in GhGalT1-silenced lines, compared with that in the wild type. 27888523 3 73 theme development 619:629 arg1 regulation 594:603 the regulation 590:603 the regulation of fiber cell development 590:629 Cotton fibers are extremely elongated single-cell trichomes on the seed epidermis; however, little is known of the molecular basis governing the regulation of fiber cell development. 27888523 4 74 theme family 704:709 arg1 GhGalT1 719:725 GhGalT1 719:725 GhGalT1 719:725 Here, we characterized the role of a CAZy glycosyltransferase 31 (GT31) family member, GhGalT1, in cotton fiber development. 27888523 4 74 theme family 704:709 arg1 member 711:716 a CAZy glycosyltransferase 31 (GT31) family member 667:716 a CAZy glycosyltransferase 31 (GT31) family member 667:716 Here, we characterized the role of a CAZy glycosyltransferase 31 (GT31) family member, GhGalT1, in cotton fiber development. 27888523 3 75 theme Cotton 449:454 arg1 trichomes 499:507 extremely elongated single-cell trichomes 467:507 extremely elongated single-cell trichomes on the seed epidermis 467:529 Cotton fibers are extremely elongated single-cell trichomes on the seed epidermis; however, little is known of the molecular basis governing the regulation of fiber cell development. 27888523 3 75 theme Cotton 449:454 arg1 fibers 456:461 Cotton fibers 449:461 Cotton fibers 449:461 Cotton fibers are extremely elongated single-cell trichomes on the seed epidermis; however, little is known of the molecular basis governing the regulation of fiber cell development. 27888523 9 76 theme enzyme 1385:1390 arg1 assay 1401:1405 An enzyme activity assay 1382:1405 An enzyme activity assay 1382:1405 An enzyme activity assay demonstrated that GhGalT1 is a β-1,3-galactosyltransferase (β-1,3-GalT) involved in biosynthesis of the β-1,3-galactan backbone of the type-II AG glycans of AGPs. 27888523 9 77 theme backbone 1526:1533 arg1 biosynthesis 1491:1502 biosynthesis 1491:1502 biosynthesis of the β-1,3-galactan backbone of the type-II AG glycans of AGPs 1491:1567 An enzyme activity assay demonstrated that GhGalT1 is a β-1,3-galactosyltransferase (β-1,3-GalT) involved in biosynthesis of the β-1,3-galactan backbone of the type-II AG glycans of AGPs. 27888523 6 78 theme carbohydrate 974:985 arg1 moieties 987:994 The carbohydrate moieties 970:994 The carbohydrate moieties of AGPs 970:1002 The carbohydrate moieties of AGPs were altered in fibers of GhGalT1 transgenic cotton. 27888523 3 79 theme fiber 608:612 arg1 development 619:629 fiber cell development 608:629 fiber cell development 608:629 Cotton fibers are extremely elongated single-cell trichomes on the seed epidermis; however, little is known of the molecular basis governing the regulation of fiber cell development. 27888523 8 80 theme wall-related 1306:1317 arg1 genes 1375:1379 the fasciclin-like AGP (FLA) backbone genes 1337:1379 the fasciclin-like AGP (FLA) backbone genes 1337:1379 Overexpression of GhGalT1 upregulates transcript levels of a broad range of cell wall-related genes, especially the fasciclin-like AGP (FLA) backbone genes. 27888523 8 80 theme wall-related 1306:1317 arg1 genes 1319:1323 cell wall-related genes 1301:1323 cell wall-related genes 1301:1323 Overexpression of GhGalT1 upregulates transcript levels of a broad range of cell wall-related genes, especially the fasciclin-like AGP (FLA) backbone genes. 27888523 0 81 theme fiber 118:122 arg1 development 124:134 fiber development 118:134 fiber development 118:134 The cotton β-galactosyltransferase 1 (GalT1) that galactosylates arabinogalactan proteins participates in controlling fiber development. 27888523 3 82 theme elongated 477:485 arg1 trichomes 499:507 extremely elongated single-cell trichomes 467:507 extremely elongated single-cell trichomes on the seed epidermis 467:529 Cotton fibers are extremely elongated single-cell trichomes on the seed epidermis; however, little is known of the molecular basis governing the regulation of fiber cell development. 27888523 3 82 theme elongated 477:485 arg1 fibers 456:461 Cotton fibers 449:461 Cotton fibers 449:461 Cotton fibers are extremely elongated single-cell trichomes on the seed epidermis; however, little is known of the molecular basis governing the regulation of fiber cell development. 27888523 9 83 theme AG 1550:1551 arg1 glycans 1553:1559 the type-II AG glycans 1538:1559 the type-II AG glycans of AGPs 1538:1567 An enzyme activity assay demonstrated that GhGalT1 is a β-1,3-galactosyltransferase (β-1,3-GalT) involved in biosynthesis of the β-1,3-galactan backbone of the type-II AG glycans of AGPs. 27888523 4 84 theme cotton 731:736 arg1 development 744:754 cotton fiber development 731:754 cotton fiber development 731:754 Here, we characterized the role of a CAZy glycosyltransferase 31 (GT31) family member, GhGalT1, in cotton fiber development. 27888523 11 85 theme cotton 1759:1764 arg1 development 1772:1782 cotton fiber development 1759:1782 cotton fiber development 1759:1782 Thus, our data demonstrate that GhGalT1 influences cotton fiber development via controlling the glycosylation of AGPs, especially FLAs. 27888523 5 86 theme overexpressing 799:812 arg1 GhGalT1 814:820 the transgenic cotton overexpressing GhGalT1 777:820 the transgenic cotton overexpressing GhGalT1 777:820 The fiber length of the transgenic cotton overexpressing GhGalT1 was shorter than that of the wild type, whereas in the GhGalT1-silenced lines there was a notable increase in fiber length compared with wild type. 27888523 10 87 theme cotton 1639:1644 arg1 members 1658:1664 other cotton GT31 family members 1633:1664 other cotton GT31 family members 1633:1664 We also show that GhGalT1 can form homo- and heterodimers with other cotton GT31 family members to facilitate AG glycan assembly of AGPs. 27888523 8 88 theme AGP 1356:1358 arg1 genes 1375:1379 the fasciclin-like AGP (FLA) backbone genes 1337:1379 the fasciclin-like AGP (FLA) backbone genes 1337:1379 Overexpression of GhGalT1 upregulates transcript levels of a broad range of cell wall-related genes, especially the fasciclin-like AGP (FLA) backbone genes. 27888523 8 88 theme AGP 1356:1358 arg1 genes 1319:1323 cell wall-related genes 1301:1323 cell wall-related genes 1301:1323 Overexpression of GhGalT1 upregulates transcript levels of a broad range of cell wall-related genes, especially the fasciclin-like AGP (FLA) backbone genes. 27888523 10 89 theme GT31 1646:1649 arg1 members 1658:1664 other cotton GT31 family members 1633:1664 other cotton GT31 family members 1633:1664 We also show that GhGalT1 can form homo- and heterodimers with other cotton GT31 family members to facilitate AG glycan assembly of AGPs. 27604766 0 0 from Role 9:12 arg1 Vaccine 76:82 a Self-Adjuvanting Vaccine 57:82 a Self-Adjuvanting Vaccine Against Meningococcal Meningitis B Disease 57:125 The Dual Role of Lipids of the Lipoproteins in Trumenba, a Self-Adjuvanting Vaccine Against Meningococcal Meningitis B Disease. 27604766 0 0 from Role 9:12 arg1 Trumenba 47:54 Trumenba 47:54 Trumenba 47:54 The Dual Role of Lipids of the Lipoproteins in Trumenba, a Self-Adjuvanting Vaccine Against Meningococcal Meningitis B Disease. 27604766 4 1 theme distinct 828:835 arg1 domain 861:866 the polypeptide domain 845:866 the polypeptide domain 845:866 Here, we describe the characterization of the vaccine antigens including the elucidation of their structure which is characterized by two distinct motifs, the polypeptide domain and the N-terminal lipid moiety. 27604766 4 1 theme distinct 828:835 arg1 motifs 837:842 two distinct motifs 824:842 two distinct motifs 824:842 Here, we describe the characterization of the vaccine antigens including the elucidation of their structure which is characterized by two distinct motifs, the polypeptide domain and the N-terminal lipid moiety. 27604766 4 1 theme distinct 828:835 arg1 moiety 893:898 the N-terminal lipid moiety 872:898 the N-terminal lipid moiety 872:898 Here, we describe the characterization of the vaccine antigens including the elucidation of their structure which is characterized by two distinct motifs, the polypeptide domain and the N-terminal lipid moiety. 27604766 5 2 theme polypeptides 1059:1070 arg1 size 1040:1043 the size 1036:1043 the size of the folded polypeptides 1036:1070 In the vaccine formulation, the lipoproteins self-associate to form micelles driven by the hydrophobicity of the lipids and limited by the size of the folded polypeptides. 27604766 1 3 theme bivalent 138:145 arg1 Trumenba 128:135 Trumenba 128:135 Trumenba (bivalent rLP2086) 128:154 Trumenba (bivalent rLP2086) is a vaccine licensed for the prevention of meningococcal meningitis disease caused by Neisseria meningitidis serogroup B (NmB) in individuals 10-25 years of age in the USA. 27604766 1 3 theme bivalent 138:145 arg1 rLP2086 147:153 bivalent rLP2086 138:153 bivalent rLP2086 138:153 Trumenba (bivalent rLP2086) is a vaccine licensed for the prevention of meningococcal meningitis disease caused by Neisseria meningitidis serogroup B (NmB) in individuals 10-25 years of age in the USA. 27604766 1 4 theme age 314:316 arg1 10-25 years 299:309 individuals 10-25 years 287:309 individuals 10-25 years of age in the USA 287:327 Trumenba (bivalent rLP2086) is a vaccine licensed for the prevention of meningococcal meningitis disease caused by Neisseria meningitidis serogroup B (NmB) in individuals 10-25 years of age in the USA. 27604766 8 5 theme adjuvant 1440:1447 arg1 role 1449:1452 an adjuvant role 1437:1452 an adjuvant role 1437:1452 This activity was lost with removal of the O-linked fatty acids, similar to removal of all lipids, demonstrating that this moiety plays an adjuvant role in immune activation. 27604766 1 6 from 10-25 years 299:309 arg1 USA 325:327 the USA 321:327 the USA 321:327 Trumenba (bivalent rLP2086) is a vaccine licensed for the prevention of meningococcal meningitis disease caused by Neisseria meningitidis serogroup B (NmB) in individuals 10-25 years of age in the USA. 27604766 7 7 from Analysis 1188:1195 arg1 assays 1256:1261 Toll-like receptor (TLR) activation assays 1220:1261 Toll-like receptor (TLR) activation assays 1220:1261 Analysis of the lipoproteins in Toll-like receptor (TLR) activation assays revealed their TLR2 agonist activity. 27604766 9 8 theme critical 1636:1643 arg1 parameters 1645:1654 critical parameters 1636:1654 critical parameters 1636:1654 The thorough understanding of the structure and function of each moiety of the lipoproteins, as well as their relationship, lays the foundation for identifying critical parameters to guide vaccine development and manufacture. 27604766 8 9 theme acids 1359:1363 arg1 removal 1329:1335 removal 1329:1335 removal of the O-linked fatty acids, similar to removal of all lipids 1329:1397 This activity was lost with removal of the O-linked fatty acids, similar to removal of all lipids, demonstrating that this moiety plays an adjuvant role in immune activation. 27604766 6 10 theme cell 1176:1179 arg1 walls 1181:1185 bacterial cell walls 1166:1185 bacterial cell walls 1166:1185 The micelles help to increase the structural stability of the lipoproteins in the absence of bacterial cell walls. 27604766 6 11 theme lipoproteins 1135:1146 arg1 stability 1118:1126 the structural stability 1103:1126 the structural stability of the lipoproteins in the absence of bacterial cell walls 1103:1185 The micelles help to increase the structural stability of the lipoproteins in the absence of bacterial cell walls. 27604766 1 12 theme Neisseria 243:251 arg1 meningitidis 253:264 Neisseria meningitidis serogroup B (NmB) 243:282 Neisseria meningitidis serogroup B (NmB) 243:282 Trumenba (bivalent rLP2086) is a vaccine licensed for the prevention of meningococcal meningitis disease caused by Neisseria meningitidis serogroup B (NmB) in individuals 10-25 years of age in the USA. 27604766 0 13 theme Self-Adjuvanting 59:74 arg1 Vaccine 76:82 a Self-Adjuvanting Vaccine 57:82 a Self-Adjuvanting Vaccine Against Meningococcal Meningitis B Disease 57:125 The Dual Role of Lipids of the Lipoproteins in Trumenba, a Self-Adjuvanting Vaccine Against Meningococcal Meningitis B Disease. 27604766 0 13 theme Self-Adjuvanting 59:74 arg1 Trumenba 47:54 Trumenba 47:54 Trumenba 47:54 The Dual Role of Lipids of the Lipoproteins in Trumenba, a Self-Adjuvanting Vaccine Against Meningococcal Meningitis B Disease. 27604766 4 14 theme antigens 744:751 arg1 characterization 712:727 the characterization 708:727 the characterization of the vaccine antigens including the elucidation of their structure which is characterized by two distinct motifs, the polypeptide domain and the N-terminal lipid moiety 708:898 Here, we describe the characterization of the vaccine antigens including the elucidation of their structure which is characterized by two distinct motifs, the polypeptide domain and the N-terminal lipid moiety. 27604766 0 15 theme Meningococcal 92:104 arg1 Disease 119:125 Meningococcal Meningitis B Disease 92:125 Meningococcal Meningitis B Disease 92:125 The Dual Role of Lipids of the Lipoproteins in Trumenba, a Self-Adjuvanting Vaccine Against Meningococcal Meningitis B Disease. 27604766 9 16 theme relationship 1586:1597 arg1 moiety 1541:1546 each moiety 1536:1546 each moiety of the lipoproteins, as well as their relationship, 1536:1598 The thorough understanding of the structure and function of each moiety of the lipoproteins, as well as their relationship, lays the foundation for identifying critical parameters to guide vaccine development and manufacture. 27604766 5 17 dep micelles 969:976 arg1 driven 978:983 driven 978:983 driven by the hydrophobicity of the lipids 978:1019 In the vaccine formulation, the lipoproteins self-associate to form micelles driven by the hydrophobicity of the lipids and limited by the size of the folded polypeptides. 27604766 5 17 dep micelles 969:976 arg1 limited 1025:1031 limited 1025:1031 limited by the size of the folded polypeptides 1025:1070 In the vaccine formulation, the lipoproteins self-associate to form micelles driven by the hydrophobicity of the lipids and limited by the size of the folded polypeptides. 27604766 9 18 theme thorough 1480:1487 arg1 understanding 1489:1501 The thorough understanding 1476:1501 The thorough understanding of the structure and function of each moiety of the lipoproteins, as well as their relationship, 1476:1598 The thorough understanding of the structure and function of each moiety of the lipoproteins, as well as their relationship, lays the foundation for identifying critical parameters to guide vaccine development and manufacture. 27604766 6 19 from stability 1118:1126 arg1 absence 1155:1161 the absence 1151:1161 the absence of bacterial cell walls 1151:1185 The micelles help to increase the structural stability of the lipoproteins in the absence of bacterial cell walls. 27604766 7 20 theme TLR2 1278:1281 arg1 activity 1291:1298 their TLR2 agonist activity 1272:1298 their TLR2 agonist activity 1272:1298 Analysis of the lipoproteins in Toll-like receptor (TLR) activation assays revealed their TLR2 agonist activity. 27604766 2 21 theme native 459:464 arg1 lipoproteins 466:477 native lipoproteins 459:477 native lipoproteins 459:477 The vaccine is composed of two factor H binding protein (fHbp) variants that were recombinantly expressed in Escherichia coli as native lipoproteins: rLP2086-A05 and rLP2086-B01. 27604766 2 21 theme native 459:464 arg1 variants 393:400 two factor H binding protein (fHbp) variants 357:400 two factor H binding protein (fHbp) variants that were recombinantly expressed in Escherichia coli as native lipoproteins: rLP2086-A05 and rLP2086-B01 357:506 The vaccine is composed of two factor H binding protein (fHbp) variants that were recombinantly expressed in Escherichia coli as native lipoproteins: rLP2086-A05 and rLP2086-B01. 27604766 3 22 theme fHbp 667:670 arg1 antigens 680:687 the fHbp vaccine antigens 663:687 the fHbp vaccine antigens 663:687 The vaccine was shown to induce potent bactericidal antibodies against a broad range of NmB isolates expressing fHbp that were different in sequence from the fHbp vaccine antigens. 27604766 8 23 link O-linked 1344:1351 arg1 acids 1359:1363 the O-linked fatty acids 1340:1363 the O-linked fatty acids 1340:1363 This activity was lost with removal of the O-linked fatty acids, similar to removal of all lipids, demonstrating that this moiety plays an adjuvant role in immune activation. 27604766 7 24 theme agonist 1283:1289 arg1 activity 1291:1298 their TLR2 agonist activity 1272:1298 their TLR2 agonist activity 1272:1298 Analysis of the lipoproteins in Toll-like receptor (TLR) activation assays revealed their TLR2 agonist activity. 27604766 0 25 theme Dual 4:7 arg1 Role 9:12 The Dual Role 0:12 The Dual Role of Lipids of the Lipoproteins in Trumenba, a Self-Adjuvanting Vaccine Against Meningococcal Meningitis B Disease. 0:126 The Dual Role of Lipids of the Lipoproteins in Trumenba, a Self-Adjuvanting Vaccine Against Meningococcal Meningitis B Disease. 27604766 3 26 theme vaccine 672:678 arg1 antigens 680:687 the fHbp vaccine antigens 663:687 the fHbp vaccine antigens 663:687 The vaccine was shown to induce potent bactericidal antibodies against a broad range of NmB isolates expressing fHbp that were different in sequence from the fHbp vaccine antigens. 27604766 2 27 dep variants 393:400 arg1 variants 393:400 two factor H binding protein (fHbp) variants 357:400 two factor H binding protein (fHbp) variants that were recombinantly expressed in Escherichia coli as native lipoproteins: rLP2086-A05 and rLP2086-B01 357:506 The vaccine is composed of two factor H binding protein (fHbp) variants that were recombinantly expressed in Escherichia coli as native lipoproteins: rLP2086-A05 and rLP2086-B01. 27604766 2 27 dep variants 393:400 arg1 rLP2086-B01 496:506 rLP2086-B01 496:506 rLP2086-B01 496:506 The vaccine is composed of two factor H binding protein (fHbp) variants that were recombinantly expressed in Escherichia coli as native lipoproteins: rLP2086-A05 and rLP2086-B01. 27604766 2 27 dep variants 393:400 arg1 rLP2086-A05 480:490 rLP2086-A05 480:490 rLP2086-A05 480:490 The vaccine is composed of two factor H binding protein (fHbp) variants that were recombinantly expressed in Escherichia coli as native lipoproteins: rLP2086-A05 and rLP2086-B01. 27604766 6 28 theme structural 1107:1116 arg1 stability 1118:1126 the structural stability 1103:1126 the structural stability of the lipoproteins in the absence of bacterial cell walls 1103:1185 The micelles help to increase the structural stability of the lipoproteins in the absence of bacterial cell walls. 27604766 9 29 theme function 1524:1531 arg1 understanding 1489:1501 The thorough understanding 1476:1501 The thorough understanding of the structure and function of each moiety of the lipoproteins, as well as their relationship, 1476:1598 The thorough understanding of the structure and function of each moiety of the lipoproteins, as well as their relationship, lays the foundation for identifying critical parameters to guide vaccine development and manufacture. 27604766 1 30 theme serogroup 266:274 arg1 NmB 279:281 NmB 279:281 NmB 279:281 Trumenba (bivalent rLP2086) is a vaccine licensed for the prevention of meningococcal meningitis disease caused by Neisseria meningitidis serogroup B (NmB) in individuals 10-25 years of age in the USA. 27604766 1 30 theme serogroup 266:274 arg1 B 276:276 serogroup B 266:276 Neisseria meningitidis serogroup B (NmB) 243:282 Trumenba (bivalent rLP2086) is a vaccine licensed for the prevention of meningococcal meningitis disease caused by Neisseria meningitidis serogroup B (NmB) in individuals 10-25 years of age in the USA. 27604766 3 31 from antigens 680:687 arg1 sequence 649:656 sequence 649:656 sequence from the fHbp vaccine antigens 649:687 The vaccine was shown to induce potent bactericidal antibodies against a broad range of NmB isolates expressing fHbp that were different in sequence from the fHbp vaccine antigens. 27604766 0 32 theme B 117:117 arg1 Disease 119:125 Meningococcal Meningitis B Disease 92:125 Meningococcal Meningitis B Disease 92:125 The Dual Role of Lipids of the Lipoproteins in Trumenba, a Self-Adjuvanting Vaccine Against Meningococcal Meningitis B Disease. 27604766 6 33 theme bacterial 1166:1174 arg1 walls 1181:1185 bacterial cell walls 1166:1185 bacterial cell walls 1166:1185 The micelles help to increase the structural stability of the lipoproteins in the absence of bacterial cell walls. 27604766 9 34 theme structure 1510:1518 arg1 understanding 1489:1501 The thorough understanding 1476:1501 The thorough understanding of the structure and function of each moiety of the lipoproteins, as well as their relationship, 1476:1598 The thorough understanding of the structure and function of each moiety of the lipoproteins, as well as their relationship, lays the foundation for identifying critical parameters to guide vaccine development and manufacture. 27604766 8 35 theme fatty 1353:1357 arg1 acids 1359:1363 the O-linked fatty acids 1340:1363 the O-linked fatty acids 1340:1363 This activity was lost with removal of the O-linked fatty acids, similar to removal of all lipids, demonstrating that this moiety plays an adjuvant role in immune activation. 27604766 2 36 theme protein 378:384 arg1 lipoproteins 466:477 native lipoproteins 459:477 native lipoproteins 459:477 The vaccine is composed of two factor H binding protein (fHbp) variants that were recombinantly expressed in Escherichia coli as native lipoproteins: rLP2086-A05 and rLP2086-B01. 27604766 2 36 theme protein 378:384 arg1 variants 393:400 two factor H binding protein (fHbp) variants 357:400 two factor H binding protein (fHbp) variants that were recombinantly expressed in Escherichia coli as native lipoproteins: rLP2086-A05 and rLP2086-B01 357:506 The vaccine is composed of two factor H binding protein (fHbp) variants that were recombinantly expressed in Escherichia coli as native lipoproteins: rLP2086-A05 and rLP2086-B01. 27604766 2 36 theme protein 378:384 arg1 rLP2086-B01 496:506 rLP2086-B01 496:506 rLP2086-B01 496:506 The vaccine is composed of two factor H binding protein (fHbp) variants that were recombinantly expressed in Escherichia coli as native lipoproteins: rLP2086-A05 and rLP2086-B01. 27604766 2 36 theme protein 378:384 arg1 rLP2086-A05 480:490 rLP2086-A05 480:490 rLP2086-A05 480:490 The vaccine is composed of two factor H binding protein (fHbp) variants that were recombinantly expressed in Escherichia coli as native lipoproteins: rLP2086-A05 and rLP2086-B01. 27604766 0 37 theme Meningitis 106:115 arg1 Disease 119:125 Meningococcal Meningitis B Disease 92:125 Meningococcal Meningitis B Disease 92:125 The Dual Role of Lipids of the Lipoproteins in Trumenba, a Self-Adjuvanting Vaccine Against Meningococcal Meningitis B Disease. 27604766 3 38 theme isolates 601:608 arg1 range 588:592 a broad range 580:592 a broad range of NmB isolates expressing fHbp that were different in sequence from the fHbp vaccine antigens 580:687 The vaccine was shown to induce potent bactericidal antibodies against a broad range of NmB isolates expressing fHbp that were different in sequence from the fHbp vaccine antigens. 27604766 5 39 theme vaccine 908:914 arg1 formulation 916:926 the vaccine formulation 904:926 the vaccine formulation 904:926 In the vaccine formulation, the lipoproteins self-associate to form micelles driven by the hydrophobicity of the lipids and limited by the size of the folded polypeptides. 27604766 2 40 theme binding 370:376 arg1 fHbp 387:390 fHbp 387:390 fHbp 387:390 The vaccine is composed of two factor H binding protein (fHbp) variants that were recombinantly expressed in Escherichia coli as native lipoproteins: rLP2086-A05 and rLP2086-B01. 27604766 2 40 theme binding 370:376 arg1 protein 378:384 factor H binding protein 361:384 two factor H binding protein (fHbp) variants that were recombinantly expressed in Escherichia coli as native lipoproteins: rLP2086-A05 and rLP2086-B01 357:506 The vaccine is composed of two factor H binding protein (fHbp) variants that were recombinantly expressed in Escherichia coli as native lipoproteins: rLP2086-A05 and rLP2086-B01. 27604766 3 41 from different 636:644 arg1 sequence 649:656 sequence 649:656 sequence from the fHbp vaccine antigens 649:687 The vaccine was shown to induce potent bactericidal antibodies against a broad range of NmB isolates expressing fHbp that were different in sequence from the fHbp vaccine antigens. 27604766 3 42 theme bactericidal 548:559 arg1 antibodies 561:570 potent bactericidal antibodies 541:570 potent bactericidal antibodies 541:570 The vaccine was shown to induce potent bactericidal antibodies against a broad range of NmB isolates expressing fHbp that were different in sequence from the fHbp vaccine antigens. 27604766 2 43 theme H 368:368 arg1 fHbp 387:390 fHbp 387:390 fHbp 387:390 The vaccine is composed of two factor H binding protein (fHbp) variants that were recombinantly expressed in Escherichia coli as native lipoproteins: rLP2086-A05 and rLP2086-B01. 27604766 2 43 theme H 368:368 arg1 protein 378:384 factor H binding protein 361:384 two factor H binding protein (fHbp) variants that were recombinantly expressed in Escherichia coli as native lipoproteins: rLP2086-A05 and rLP2086-B01 357:506 The vaccine is composed of two factor H binding protein (fHbp) variants that were recombinantly expressed in Escherichia coli as native lipoproteins: rLP2086-A05 and rLP2086-B01. 27604766 0 44 theme Lipids 17:22 arg1 Role 9:12 The Dual Role 0:12 The Dual Role of Lipids of the Lipoproteins in Trumenba, a Self-Adjuvanting Vaccine Against Meningococcal Meningitis B Disease. 0:126 The Dual Role of Lipids of the Lipoproteins in Trumenba, a Self-Adjuvanting Vaccine Against Meningococcal Meningitis B Disease. 27604766 3 45 from sequence 649:656 arg1 different 636:644 different 636:644 different 636:644 The vaccine was shown to induce potent bactericidal antibodies against a broad range of NmB isolates expressing fHbp that were different in sequence from the fHbp vaccine antigens. 27604766 7 46 from lipoproteins 1204:1215 arg1 assays 1256:1261 Toll-like receptor (TLR) activation assays 1220:1261 Toll-like receptor (TLR) activation assays 1220:1261 Analysis of the lipoproteins in Toll-like receptor (TLR) activation assays revealed their TLR2 agonist activity. 27604766 6 47 theme walls 1181:1185 arg1 absence 1155:1161 the absence 1151:1161 the absence of bacterial cell walls 1151:1185 The micelles help to increase the structural stability of the lipoproteins in the absence of bacterial cell walls. 27604766 2 48 theme factor 361:366 arg1 fHbp 387:390 fHbp 387:390 fHbp 387:390 The vaccine is composed of two factor H binding protein (fHbp) variants that were recombinantly expressed in Escherichia coli as native lipoproteins: rLP2086-A05 and rLP2086-B01. 27604766 2 48 theme factor 361:366 arg1 protein 378:384 factor H binding protein 361:384 two factor H binding protein (fHbp) variants that were recombinantly expressed in Escherichia coli as native lipoproteins: rLP2086-A05 and rLP2086-B01 357:506 The vaccine is composed of two factor H binding protein (fHbp) variants that were recombinantly expressed in Escherichia coli as native lipoproteins: rLP2086-A05 and rLP2086-B01. 27604766 0 49 theme Lipoproteins 31:42 arg1 Lipids 17:22 Lipids 17:22 Lipids of the Lipoproteins 17:42 The Dual Role of Lipids of the Lipoproteins in Trumenba, a Self-Adjuvanting Vaccine Against Meningococcal Meningitis B Disease. 27604766 8 50 theme immune 1457:1462 arg1 activation 1464:1473 immune activation 1457:1473 immune activation 1457:1473 This activity was lost with removal of the O-linked fatty acids, similar to removal of all lipids, demonstrating that this moiety plays an adjuvant role in immune activation. 27604766 4 51 theme polypeptide 849:859 arg1 domain 861:866 the polypeptide domain 845:866 the polypeptide domain 845:866 Here, we describe the characterization of the vaccine antigens including the elucidation of their structure which is characterized by two distinct motifs, the polypeptide domain and the N-terminal lipid moiety. 27604766 4 51 theme polypeptide 849:859 arg1 motifs 837:842 two distinct motifs 824:842 two distinct motifs 824:842 Here, we describe the characterization of the vaccine antigens including the elucidation of their structure which is characterized by two distinct motifs, the polypeptide domain and the N-terminal lipid moiety. 27604766 3 52 theme NmB 597:599 arg1 isolates 601:608 NmB isolates 597:608 NmB isolates expressing fHbp that were different in sequence from the fHbp vaccine antigens 597:687 The vaccine was shown to induce potent bactericidal antibodies against a broad range of NmB isolates expressing fHbp that were different in sequence from the fHbp vaccine antigens. 27604766 4 53 theme structure 788:796 arg1 elucidation 767:777 the elucidation 763:777 the elucidation of their structure which is characterized by two distinct motifs, the polypeptide domain and the N-terminal lipid moiety 763:898 Here, we describe the characterization of the vaccine antigens including the elucidation of their structure which is characterized by two distinct motifs, the polypeptide domain and the N-terminal lipid moiety. 27604766 5 54 theme folded 1052:1057 arg1 polypeptides 1059:1070 the folded polypeptides 1048:1070 the folded polypeptides 1048:1070 In the vaccine formulation, the lipoproteins self-associate to form micelles driven by the hydrophobicity of the lipids and limited by the size of the folded polypeptides. 27604766 7 55 theme receptor 1230:1237 arg1 assays 1256:1261 Toll-like receptor (TLR) activation assays 1220:1261 Toll-like receptor (TLR) activation assays 1220:1261 Analysis of the lipoproteins in Toll-like receptor (TLR) activation assays revealed their TLR2 agonist activity. 27604766 4 56 theme lipid 887:891 arg1 motifs 837:842 two distinct motifs 824:842 two distinct motifs 824:842 Here, we describe the characterization of the vaccine antigens including the elucidation of their structure which is characterized by two distinct motifs, the polypeptide domain and the N-terminal lipid moiety. 27604766 4 56 theme lipid 887:891 arg1 moiety 893:898 the N-terminal lipid moiety 872:898 the N-terminal lipid moiety 872:898 Here, we describe the characterization of the vaccine antigens including the elucidation of their structure which is characterized by two distinct motifs, the polypeptide domain and the N-terminal lipid moiety. 27604766 1 57 theme individuals 287:297 arg1 10-25 years 299:309 individuals 10-25 years 287:309 individuals 10-25 years of age in the USA 287:327 Trumenba (bivalent rLP2086) is a vaccine licensed for the prevention of meningococcal meningitis disease caused by Neisseria meningitidis serogroup B (NmB) in individuals 10-25 years of age in the USA. 27604766 4 58 theme N-terminal 876:885 arg1 motifs 837:842 two distinct motifs 824:842 two distinct motifs 824:842 Here, we describe the characterization of the vaccine antigens including the elucidation of their structure which is characterized by two distinct motifs, the polypeptide domain and the N-terminal lipid moiety. 27604766 4 58 theme N-terminal 876:885 arg1 moiety 893:898 the N-terminal lipid moiety 872:898 the N-terminal lipid moiety 872:898 Here, we describe the characterization of the vaccine antigens including the elucidation of their structure which is characterized by two distinct motifs, the polypeptide domain and the N-terminal lipid moiety. 27604766 3 59 theme potent 541:546 arg1 antibodies 561:570 potent bactericidal antibodies 541:570 potent bactericidal antibodies 541:570 The vaccine was shown to induce potent bactericidal antibodies against a broad range of NmB isolates expressing fHbp that were different in sequence from the fHbp vaccine antigens. 27604766 8 60 theme lipids 1392:1397 arg1 removal 1377:1383 removal 1377:1383 removal of all lipids 1377:1397 This activity was lost with removal of the O-linked fatty acids, similar to removal of all lipids, demonstrating that this moiety plays an adjuvant role in immune activation. 27604766 1 61 dep meningitidis 253:264 arg1 NmB 279:281 NmB 279:281 NmB 279:281 Trumenba (bivalent rLP2086) is a vaccine licensed for the prevention of meningococcal meningitis disease caused by Neisseria meningitidis serogroup B (NmB) in individuals 10-25 years of age in the USA. 27604766 1 61 dep meningitidis 253:264 arg1 B 276:276 serogroup B 266:276 Neisseria meningitidis serogroup B (NmB) 243:282 Trumenba (bivalent rLP2086) is a vaccine licensed for the prevention of meningococcal meningitis disease caused by Neisseria meningitidis serogroup B (NmB) in individuals 10-25 years of age in the USA. 27604766 3 62 theme broad 582:586 arg1 range 588:592 a broad range 580:592 a broad range of NmB isolates expressing fHbp that were different in sequence from the fHbp vaccine antigens 580:687 The vaccine was shown to induce potent bactericidal antibodies against a broad range of NmB isolates expressing fHbp that were different in sequence from the fHbp vaccine antigens. 27604766 7 63 from assays 1256:1261 arg1 Analysis 1188:1195 Analysis 1188:1195 Analysis of the lipoproteins in Toll-like receptor (TLR) activation assays 1188:1261 Analysis of the lipoproteins in Toll-like receptor (TLR) activation assays revealed their TLR2 agonist activity. 27604766 9 64 theme vaccine 1665:1671 arg1 development 1673:1683 vaccine development 1665:1683 vaccine development 1665:1683 The thorough understanding of the structure and function of each moiety of the lipoproteins, as well as their relationship, lays the foundation for identifying critical parameters to guide vaccine development and manufacture. 27604766 5 65 theme lipids 1014:1019 arg1 hydrophobicity 992:1005 the hydrophobicity 988:1005 the hydrophobicity of the lipids 988:1019 In the vaccine formulation, the lipoproteins self-associate to form micelles driven by the hydrophobicity of the lipids and limited by the size of the folded polypeptides. 27604766 4 66 theme vaccine 736:742 arg1 antigens 744:751 the vaccine antigens 732:751 the vaccine antigens including the elucidation of their structure which is characterized by two distinct motifs, the polypeptide domain and the N-terminal lipid moiety 732:898 Here, we describe the characterization of the vaccine antigens including the elucidation of their structure which is characterized by two distinct motifs, the polypeptide domain and the N-terminal lipid moiety. 27604766 4 66 theme vaccine 736:742 arg1 elucidation 767:777 the elucidation 763:777 the elucidation of their structure which is characterized by two distinct motifs, the polypeptide domain and the N-terminal lipid moiety 763:898 Here, we describe the characterization of the vaccine antigens including the elucidation of their structure which is characterized by two distinct motifs, the polypeptide domain and the N-terminal lipid moiety. 27604766 7 67 theme Toll-like 1220:1228 arg1 TLR 1240:1242 TLR 1240:1242 TLR 1240:1242 Analysis of the lipoproteins in Toll-like receptor (TLR) activation assays revealed their TLR2 agonist activity. 27604766 7 67 theme Toll-like 1220:1228 arg1 receptor 1230:1237 Toll-like receptor 1220:1237 Toll-like receptor (TLR) activation assays 1220:1261 Analysis of the lipoproteins in Toll-like receptor (TLR) activation assays revealed their TLR2 agonist activity. 27604766 1 68 theme meningococcal 200:212 arg1 disease 225:231 meningococcal meningitis disease 200:231 meningococcal meningitis disease caused by Neisseria meningitidis serogroup B (NmB) 200:282 Trumenba (bivalent rLP2086) is a vaccine licensed for the prevention of meningococcal meningitis disease caused by Neisseria meningitidis serogroup B (NmB) in individuals 10-25 years of age in the USA. 27604766 9 69 dep structure 1510:1518 arg1 the 1506:1508 the 1506:1508 the 1506:1508 The thorough understanding of the structure and function of each moiety of the lipoproteins, as well as their relationship, lays the foundation for identifying critical parameters to guide vaccine development and manufacture. 27604766 9 70 theme lipoproteins 1555:1566 arg1 moiety 1541:1546 each moiety 1536:1546 each moiety of the lipoproteins, as well as their relationship, 1536:1598 The thorough understanding of the structure and function of each moiety of the lipoproteins, as well as their relationship, lays the foundation for identifying critical parameters to guide vaccine development and manufacture. 27604766 7 71 theme activation 1245:1254 arg1 assays 1256:1261 Toll-like receptor (TLR) activation assays 1220:1261 Toll-like receptor (TLR) activation assays 1220:1261 Analysis of the lipoproteins in Toll-like receptor (TLR) activation assays revealed their TLR2 agonist activity. 27604766 8 72 theme O-linked 1344:1351 arg1 acids 1359:1363 the O-linked fatty acids 1340:1363 the O-linked fatty acids 1340:1363 This activity was lost with removal of the O-linked fatty acids, similar to removal of all lipids, demonstrating that this moiety plays an adjuvant role in immune activation. 27604766 1 73 theme meningitis 214:223 arg1 disease 225:231 meningococcal meningitis disease 200:231 meningococcal meningitis disease caused by Neisseria meningitidis serogroup B (NmB) 200:282 Trumenba (bivalent rLP2086) is a vaccine licensed for the prevention of meningococcal meningitis disease caused by Neisseria meningitidis serogroup B (NmB) in individuals 10-25 years of age in the USA. 27604766 8 74 theme similar 1366:1372 arg1 acids 1359:1363 the O-linked fatty acids 1340:1363 the O-linked fatty acids 1340:1363 This activity was lost with removal of the O-linked fatty acids, similar to removal of all lipids, demonstrating that this moiety plays an adjuvant role in immune activation. 27604766 7 75 theme lipoproteins 1204:1215 arg1 Analysis 1188:1195 Analysis 1188:1195 Analysis of the lipoproteins in Toll-like receptor (TLR) activation assays 1188:1261 Analysis of the lipoproteins in Toll-like receptor (TLR) activation assays revealed their TLR2 agonist activity. 27604766 9 76 theme moiety 1541:1546 arg1 function 1524:1531 function 1524:1531 function 1524:1531 The thorough understanding of the structure and function of each moiety of the lipoproteins, as well as their relationship, lays the foundation for identifying critical parameters to guide vaccine development and manufacture. 27604766 9 76 theme moiety 1541:1546 arg1 structure 1510:1518 structure 1510:1518 structure 1510:1518 The thorough understanding of the structure and function of each moiety of the lipoproteins, as well as their relationship, lays the foundation for identifying critical parameters to guide vaccine development and manufacture. 27604766 1 77 theme disease 225:231 arg1 prevention 186:195 the prevention 182:195 the prevention of meningococcal meningitis disease caused by Neisseria meningitidis serogroup B (NmB) 182:282 Trumenba (bivalent rLP2086) is a vaccine licensed for the prevention of meningococcal meningitis disease caused by Neisseria meningitidis serogroup B (NmB) in individuals 10-25 years of age in the USA. 27624963 3 0 with backbone 476:483 arg1 β-1,3- 499:504 sporadic β-1,3- 490:504 sporadic β-1,3- 490:504 β-Glucans have a conserved β-1,3-glucan backbone with sporadic β-1,3- or β-1,6-linked short glucans as branches at the 6-O-positions, and the branches may play a critical role in their immunologic functions. 27624963 3 0 with backbone 476:483 arg1 glucans 528:534 β-1,6-linked short glucans 509:534 β-1,6-linked short glucans 509:534 β-Glucans have a conserved β-1,3-glucan backbone with sporadic β-1,3- or β-1,6-linked short glucans as branches at the 6-O-positions, and the branches may play a critical role in their immunologic functions. 27624963 3 1 link β-1,6-linked 509:520 arg1 glucans 528:534 β-1,6-linked short glucans 509:534 β-1,6-linked short glucans 509:534 β-Glucans have a conserved β-1,3-glucan backbone with sporadic β-1,3- or β-1,6-linked short glucans as branches at the 6-O-positions, and the branches may play a critical role in their immunologic functions. 27624963 9 2 theme antifungal 1657:1666 arg1 design 1676:1681 antifungal vaccine design 1657:1681 antifungal vaccine design 1657:1681 Thus, branched oligo-β-glucans were identified as functional epitopes for antifungal vaccine design and the corresponding protein conjugates as promising antifungal vaccine candidates. 27624963 8 3 from infection 1564:1572 arg1 mice 1577:1580 mice 1577:1580 mice 1577:1580 Most importantly, these conjugates elicited effective protection against systemic Candida albicans infection in mice. 27624963 9 4 theme vaccine 1748:1754 arg1 candidates 1756:1765 promising antifungal vaccine candidates 1727:1765 promising antifungal vaccine candidates 1727:1765 Thus, branched oligo-β-glucans were identified as functional epitopes for antifungal vaccine design and the corresponding protein conjugates as promising antifungal vaccine candidates. 27624963 9 4 theme vaccine 1748:1754 arg1 oligo-β-glucans 1598:1612 branched oligo-β-glucans 1589:1612 branched oligo-β-glucans 1589:1612 Thus, branched oligo-β-glucans were identified as functional epitopes for antifungal vaccine design and the corresponding protein conjugates as promising antifungal vaccine candidates. 27624963 4 5 theme β-glucan 765:772 arg1 oligosaccharides 774:789 three branched β-glucan oligosaccharides 750:789 three branched β-glucan oligosaccharides 750:789 To study the immunologic properties of branched β-glucans and develop β-glucan-based antifungal vaccines, three branched β-glucan oligosaccharides with 6-O-linked β-1,6-tetraglucose, β-1,3-diglucose, and β-1,3-tetraglucose branches on a β-1,3-nonaglucan backbone, which mimic the structural epitopes of natural β-glucans, were synthesized and coupled with keyhole limpet hemocyanin (KLH) to form novel synthetic conjugate vaccines. 27624963 4 6 theme synthetic 1046:1054 arg1 vaccines 1066:1073 novel synthetic conjugate vaccines 1040:1073 novel synthetic conjugate vaccines 1040:1073 To study the immunologic properties of branched β-glucans and develop β-glucan-based antifungal vaccines, three branched β-glucan oligosaccharides with 6-O-linked β-1,6-tetraglucose, β-1,3-diglucose, and β-1,3-tetraglucose branches on a β-1,3-nonaglucan backbone, which mimic the structural epitopes of natural β-glucans, were synthesized and coupled with keyhole limpet hemocyanin (KLH) to form novel synthetic conjugate vaccines. 27624963 7 7 theme natural 1429:1435 arg1 cells 1458:1462 natural β-glucans and fungal cells 1429:1462 natural β-glucans and fungal cells 1429:1462 Moreover, antibodies induced by the synthetic oligosaccharide-KLH conjugates were able to recognize and bind to natural β-glucans and fungal cells. 27624963 8 8 theme systemic 1538:1545 arg1 infection 1564:1572 systemic Candida albicans infection 1538:1572 systemic Candida albicans infection in mice 1538:1580 Most importantly, these conjugates elicited effective protection against systemic Candida albicans infection in mice. 27624963 1 9 theme rapid 79:83 arg1 growth 85:90 the rapid growth 75:90 the rapid growth in fungal infections and drug-resistant fungal strains 75:145 With the rapid growth in fungal infections and drug-resistant fungal strains, antifungal vaccines have become an especially attractive strategy to tackle this important health problem. 27624963 1 10 from growth 85:90 arg1 strains 139:145 drug-resistant fungal strains 117:145 drug-resistant fungal strains 117:145 With the rapid growth in fungal infections and drug-resistant fungal strains, antifungal vaccines have become an especially attractive strategy to tackle this important health problem. 27624963 1 10 from growth 85:90 arg1 infections 102:111 fungal infections 95:111 fungal infections 95:111 With the rapid growth in fungal infections and drug-resistant fungal strains, antifungal vaccines have become an especially attractive strategy to tackle this important health problem. 27624963 4 11 theme novel 1040:1044 arg1 vaccines 1066:1073 novel synthetic conjugate vaccines 1040:1073 novel synthetic conjugate vaccines 1040:1073 To study the immunologic properties of branched β-glucans and develop β-glucan-based antifungal vaccines, three branched β-glucan oligosaccharides with 6-O-linked β-1,6-tetraglucose, β-1,3-diglucose, and β-1,3-tetraglucose branches on a β-1,3-nonaglucan backbone, which mimic the structural epitopes of natural β-glucans, were synthesized and coupled with keyhole limpet hemocyanin (KLH) to form novel synthetic conjugate vaccines. 27624963 4 12 with oligosaccharides 774:789 arg1 branches 867:874 6-O-linked β-1,6-tetraglucose, β-1,3-diglucose, and β-1,3-tetraglucose branches 796:874 6-O-linked β-1,6-tetraglucose, β-1,3-diglucose, and β-1,3-tetraglucose branches 796:874 To study the immunologic properties of branched β-glucans and develop β-glucan-based antifungal vaccines, three branched β-glucan oligosaccharides with 6-O-linked β-1,6-tetraglucose, β-1,3-diglucose, and β-1,3-tetraglucose branches on a β-1,3-nonaglucan backbone, which mimic the structural epitopes of natural β-glucans, were synthesized and coupled with keyhole limpet hemocyanin (KLH) to form novel synthetic conjugate vaccines. 27624963 4 13 theme branched 756:763 arg1 oligosaccharides 774:789 three branched β-glucan oligosaccharides 750:789 three branched β-glucan oligosaccharides 750:789 To study the immunologic properties of branched β-glucans and develop β-glucan-based antifungal vaccines, three branched β-glucan oligosaccharides with 6-O-linked β-1,6-tetraglucose, β-1,3-diglucose, and β-1,3-tetraglucose branches on a β-1,3-nonaglucan backbone, which mimic the structural epitopes of natural β-glucans, were synthesized and coupled with keyhole limpet hemocyanin (KLH) to form novel synthetic conjugate vaccines. 27624963 3 14 theme critical 598:605 arg1 role 607:610 a critical role 596:610 a critical role 596:610 β-Glucans have a conserved β-1,3-glucan backbone with sporadic β-1,3- or β-1,6-linked short glucans as branches at the 6-O-positions, and the branches may play a critical role in their immunologic functions. 27624963 3 15 theme immunologic 621:631 arg1 functions 633:641 their immunologic functions 615:641 their immunologic functions 615:641 β-Glucans have a conserved β-1,3-glucan backbone with sporadic β-1,3- or β-1,6-linked short glucans as branches at the 6-O-positions, and the branches may play a critical role in their immunologic functions. 27624963 4 16 theme 6-O-linked 796:805 arg1 branches 867:874 6-O-linked β-1,6-tetraglucose, β-1,3-diglucose, and β-1,3-tetraglucose branches 796:874 6-O-linked β-1,6-tetraglucose, β-1,3-diglucose, and β-1,3-tetraglucose branches 796:874 To study the immunologic properties of branched β-glucans and develop β-glucan-based antifungal vaccines, three branched β-glucan oligosaccharides with 6-O-linked β-1,6-tetraglucose, β-1,3-diglucose, and β-1,3-tetraglucose branches on a β-1,3-nonaglucan backbone, which mimic the structural epitopes of natural β-glucans, were synthesized and coupled with keyhole limpet hemocyanin (KLH) to form novel synthetic conjugate vaccines. 27624963 4 17 theme β-glucans 955:963 arg1 epitopes 935:942 the structural epitopes 920:942 the structural epitopes of natural β-glucans 920:963 To study the immunologic properties of branched β-glucans and develop β-glucan-based antifungal vaccines, three branched β-glucan oligosaccharides with 6-O-linked β-1,6-tetraglucose, β-1,3-diglucose, and β-1,3-tetraglucose branches on a β-1,3-nonaglucan backbone, which mimic the structural epitopes of natural β-glucans, were synthesized and coupled with keyhole limpet hemocyanin (KLH) to form novel synthetic conjugate vaccines. 27624963 4 18 theme branched 683:690 arg1 β-glucans 692:700 branched β-glucans 683:700 branched β-glucans 683:700 To study the immunologic properties of branched β-glucans and develop β-glucan-based antifungal vaccines, three branched β-glucan oligosaccharides with 6-O-linked β-1,6-tetraglucose, β-1,3-diglucose, and β-1,3-tetraglucose branches on a β-1,3-nonaglucan backbone, which mimic the structural epitopes of natural β-glucans, were synthesized and coupled with keyhole limpet hemocyanin (KLH) to form novel synthetic conjugate vaccines. 27624963 4 19 link 6-O-linked 796:805 arg1 branches 867:874 6-O-linked β-1,6-tetraglucose, β-1,3-diglucose, and β-1,3-tetraglucose branches 796:874 6-O-linked β-1,6-tetraglucose, β-1,3-diglucose, and β-1,3-tetraglucose branches 796:874 To study the immunologic properties of branched β-glucans and develop β-glucan-based antifungal vaccines, three branched β-glucan oligosaccharides with 6-O-linked β-1,6-tetraglucose, β-1,3-diglucose, and β-1,3-tetraglucose branches on a β-1,3-nonaglucan backbone, which mimic the structural epitopes of natural β-glucans, were synthesized and coupled with keyhole limpet hemocyanin (KLH) to form novel synthetic conjugate vaccines. 27624963 1 20 theme attractive 194:203 arg1 strategy 205:212 an especially attractive strategy 180:212 an especially attractive strategy to tackle this important health problem 180:252 With the rapid growth in fungal infections and drug-resistant fungal strains, antifungal vaccines have become an especially attractive strategy to tackle this important health problem. 27624963 4 21 theme conjugate 1056:1064 arg1 vaccines 1066:1073 novel synthetic conjugate vaccines 1040:1073 novel synthetic conjugate vaccines 1040:1073 To study the immunologic properties of branched β-glucans and develop β-glucan-based antifungal vaccines, three branched β-glucan oligosaccharides with 6-O-linked β-1,6-tetraglucose, β-1,3-diglucose, and β-1,3-tetraglucose branches on a β-1,3-nonaglucan backbone, which mimic the structural epitopes of natural β-glucans, were synthesized and coupled with keyhole limpet hemocyanin (KLH) to form novel synthetic conjugate vaccines. 27624963 4 22 theme natural 947:953 arg1 β-glucans 955:963 natural β-glucans 947:963 natural β-glucans 947:963 To study the immunologic properties of branched β-glucans and develop β-glucan-based antifungal vaccines, three branched β-glucan oligosaccharides with 6-O-linked β-1,6-tetraglucose, β-1,3-diglucose, and β-1,3-tetraglucose branches on a β-1,3-nonaglucan backbone, which mimic the structural epitopes of natural β-glucans, were synthesized and coupled with keyhole limpet hemocyanin (KLH) to form novel synthetic conjugate vaccines. 27624963 1 23 theme fungal 95:100 arg1 infections 102:111 fungal infections 95:111 fungal infections 95:111 With the rapid growth in fungal infections and drug-resistant fungal strains, antifungal vaccines have become an especially attractive strategy to tackle this important health problem. 27624963 9 24 theme promising 1727:1735 arg1 candidates 1756:1765 promising antifungal vaccine candidates 1727:1765 promising antifungal vaccine candidates 1727:1765 Thus, branched oligo-β-glucans were identified as functional epitopes for antifungal vaccine design and the corresponding protein conjugates as promising antifungal vaccine candidates. 27624963 9 24 theme promising 1727:1735 arg1 oligo-β-glucans 1598:1612 branched oligo-β-glucans 1589:1612 branched oligo-β-glucans 1589:1612 Thus, branched oligo-β-glucans were identified as functional epitopes for antifungal vaccine design and the corresponding protein conjugates as promising antifungal vaccine candidates. 27624963 4 25 theme β-glucan-based 714:727 arg1 vaccines 740:747 β-glucan-based antifungal vaccines 714:747 β-glucan-based antifungal vaccines 714:747 To study the immunologic properties of branched β-glucans and develop β-glucan-based antifungal vaccines, three branched β-glucan oligosaccharides with 6-O-linked β-1,6-tetraglucose, β-1,3-diglucose, and β-1,3-tetraglucose branches on a β-1,3-nonaglucan backbone, which mimic the structural epitopes of natural β-glucans, were synthesized and coupled with keyhole limpet hemocyanin (KLH) to form novel synthetic conjugate vaccines. 27624963 0 26 theme Oligo-β-glucan-Based 13:32 arg1 Vaccines 60:67 6-O-Branched Oligo-β-glucan-Based Antifungal Glycoconjugate Vaccines 0:67 6-O-Branched Oligo-β-glucan-Based Antifungal Glycoconjugate Vaccines 0:67 6-O-Branched Oligo-β-glucan-Based Antifungal Glycoconjugate Vaccines. 27624963 6 27 theme β-glucan 1245:1252 arg1 backbone 1254:1261 the β-glucan backbone 1241:1261 the β-glucan backbone 1241:1261 It was also discovered that the number, size, and structure of branches linked to the β-glucan backbone had a significant impact on the immunologic property. 27624963 9 28 theme corresponding 1691:1703 arg1 conjugates 1713:1722 the corresponding protein conjugates 1687:1722 the corresponding protein conjugates 1687:1722 Thus, branched oligo-β-glucans were identified as functional epitopes for antifungal vaccine design and the corresponding protein conjugates as promising antifungal vaccine candidates. 27624963 2 29 theme cell 361:364 arg1 surfaces 366:373 fungal cell surfaces 354:373 fungal cell surfaces 354:373 β-Glucans, a class of extracellular carbohydrate antigens abundantly and consistently expressed on fungal cell surfaces, are intriguing epitopes for antifungal vaccine development. 27624963 7 30 theme oligosaccharide-KLH 1363:1381 arg1 conjugates 1383:1392 the synthetic oligosaccharide-KLH conjugates 1349:1392 the synthetic oligosaccharide-KLH conjugates 1349:1392 Moreover, antibodies induced by the synthetic oligosaccharide-KLH conjugates were able to recognize and bind to natural β-glucans and fungal cells. 27624963 9 31 theme antifungal 1737:1746 arg1 candidates 1756:1765 promising antifungal vaccine candidates 1727:1765 promising antifungal vaccine candidates 1727:1765 Thus, branched oligo-β-glucans were identified as functional epitopes for antifungal vaccine design and the corresponding protein conjugates as promising antifungal vaccine candidates. 27624963 9 31 theme antifungal 1737:1746 arg1 oligo-β-glucans 1598:1612 branched oligo-β-glucans 1589:1612 branched oligo-β-glucans 1589:1612 Thus, branched oligo-β-glucans were identified as functional epitopes for antifungal vaccine design and the corresponding protein conjugates as promising antifungal vaccine candidates. 27624963 0 32 theme 6-O-Branched 0:11 arg1 Vaccines 60:67 6-O-Branched Oligo-β-glucan-Based Antifungal Glycoconjugate Vaccines 0:67 6-O-Branched Oligo-β-glucan-Based Antifungal Glycoconjugate Vaccines 0:67 6-O-Branched Oligo-β-glucan-Based Antifungal Glycoconjugate Vaccines. 27624963 3 33 contain have 446:449 arg1 β-Glucans 436:444 β-Glucans 436:444 β-Glucans 436:444 β-Glucans have a conserved β-1,3-glucan backbone with sporadic β-1,3- or β-1,6-linked short glucans as branches at the 6-O-positions, and the branches may play a critical role in their immunologic functions. 27624963 3 33 contain have 446:449 arg2 backbone 476:483 a conserved β-1,3-glucan backbone 451:483 a conserved β-1,3-glucan backbone with sporadic β-1,3- or β-1,6-linked short glucans 451:534 β-Glucans have a conserved β-1,3-glucan backbone with sporadic β-1,3- or β-1,6-linked short glucans as branches at the 6-O-positions, and the branches may play a critical role in their immunologic functions. 27624963 3 33 contain have 446:449 arg2 branches 539:546 branches 539:546 branches at the 6-O-positions 539:567 β-Glucans have a conserved β-1,3-glucan backbone with sporadic β-1,3- or β-1,6-linked short glucans as branches at the 6-O-positions, and the branches may play a critical role in their immunologic functions. 27624963 2 34 theme fungal 354:359 arg1 surfaces 366:373 fungal cell surfaces 354:373 fungal cell surfaces 354:373 β-Glucans, a class of extracellular carbohydrate antigens abundantly and consistently expressed on fungal cell surfaces, are intriguing epitopes for antifungal vaccine development. 27624963 5 35 from responses 1140:1148 arg1 mice 1153:1156 mice 1153:1156 mice 1153:1156 These glycoconjugates were proved to elicit strong IgG antibody responses in mice. 27624963 3 36 theme sporadic 490:497 arg1 β-1,3- 499:504 sporadic β-1,3- 490:504 sporadic β-1,3- 490:504 β-Glucans have a conserved β-1,3-glucan backbone with sporadic β-1,3- or β-1,6-linked short glucans as branches at the 6-O-positions, and the branches may play a critical role in their immunologic functions. 27624963 0 37 theme Glycoconjugate 45:58 arg1 Vaccines 60:67 6-O-Branched Oligo-β-glucan-Based Antifungal Glycoconjugate Vaccines 0:67 6-O-Branched Oligo-β-glucan-Based Antifungal Glycoconjugate Vaccines 0:67 6-O-Branched Oligo-β-glucan-Based Antifungal Glycoconjugate Vaccines. 27624963 4 38 theme β-1,3-diglucose 827:841 arg1 branches 867:874 6-O-linked β-1,6-tetraglucose, β-1,3-diglucose, and β-1,3-tetraglucose branches 796:874 6-O-linked β-1,6-tetraglucose, β-1,3-diglucose, and β-1,3-tetraglucose branches 796:874 To study the immunologic properties of branched β-glucans and develop β-glucan-based antifungal vaccines, three branched β-glucan oligosaccharides with 6-O-linked β-1,6-tetraglucose, β-1,3-diglucose, and β-1,3-tetraglucose branches on a β-1,3-nonaglucan backbone, which mimic the structural epitopes of natural β-glucans, were synthesized and coupled with keyhole limpet hemocyanin (KLH) to form novel synthetic conjugate vaccines. 27624963 3 39 from 6-O-positions 555:567 arg1 branches 539:546 branches 539:546 branches at the 6-O-positions 539:567 β-Glucans have a conserved β-1,3-glucan backbone with sporadic β-1,3- or β-1,6-linked short glucans as branches at the 6-O-positions, and the branches may play a critical role in their immunologic functions. 27624963 3 39 from 6-O-positions 555:567 arg1 backbone 476:483 a conserved β-1,3-glucan backbone 451:483 a conserved β-1,3-glucan backbone with sporadic β-1,3- or β-1,6-linked short glucans 451:534 β-Glucans have a conserved β-1,3-glucan backbone with sporadic β-1,3- or β-1,6-linked short glucans as branches at the 6-O-positions, and the branches may play a critical role in their immunologic functions. 27624963 1 40 theme drug-resistant 117:130 arg1 strains 139:145 drug-resistant fungal strains 117:145 drug-resistant fungal strains 117:145 With the rapid growth in fungal infections and drug-resistant fungal strains, antifungal vaccines have become an especially attractive strategy to tackle this important health problem. 27624963 5 41 theme IgG 1127:1129 arg1 responses 1140:1148 strong IgG antibody responses 1120:1148 strong IgG antibody responses in mice 1120:1156 These glycoconjugates were proved to elicit strong IgG antibody responses in mice. 27624963 4 42 theme β-glucans 692:700 arg1 properties 669:678 the immunologic properties 653:678 the immunologic properties of branched β-glucans 653:700 To study the immunologic properties of branched β-glucans and develop β-glucan-based antifungal vaccines, three branched β-glucan oligosaccharides with 6-O-linked β-1,6-tetraglucose, β-1,3-diglucose, and β-1,3-tetraglucose branches on a β-1,3-nonaglucan backbone, which mimic the structural epitopes of natural β-glucans, were synthesized and coupled with keyhole limpet hemocyanin (KLH) to form novel synthetic conjugate vaccines. 27624963 0 43 theme Antifungal 34:43 arg1 Vaccines 60:67 6-O-Branched Oligo-β-glucan-Based Antifungal Glycoconjugate Vaccines 0:67 6-O-Branched Oligo-β-glucan-Based Antifungal Glycoconjugate Vaccines 0:67 6-O-Branched Oligo-β-glucan-Based Antifungal Glycoconjugate Vaccines. 27624963 4 44 theme β-1,3-nonaglucan 881:896 arg1 backbone 898:905 a β-1,3-nonaglucan backbone 879:905 a β-1,3-nonaglucan backbone 879:905 To study the immunologic properties of branched β-glucans and develop β-glucan-based antifungal vaccines, three branched β-glucan oligosaccharides with 6-O-linked β-1,6-tetraglucose, β-1,3-diglucose, and β-1,3-tetraglucose branches on a β-1,3-nonaglucan backbone, which mimic the structural epitopes of natural β-glucans, were synthesized and coupled with keyhole limpet hemocyanin (KLH) to form novel synthetic conjugate vaccines. 27624963 6 45 theme significant 1269:1279 arg1 impact 1281:1286 a significant impact 1267:1286 a significant impact 1267:1286 It was also discovered that the number, size, and structure of branches linked to the β-glucan backbone had a significant impact on the immunologic property. 27624963 1 46 theme fungal 132:137 arg1 strains 139:145 drug-resistant fungal strains 117:145 drug-resistant fungal strains 117:145 With the rapid growth in fungal infections and drug-resistant fungal strains, antifungal vaccines have become an especially attractive strategy to tackle this important health problem. 27624963 9 47 theme vaccine 1668:1674 arg1 design 1676:1681 antifungal vaccine design 1657:1681 antifungal vaccine design 1657:1681 Thus, branched oligo-β-glucans were identified as functional epitopes for antifungal vaccine design and the corresponding protein conjugates as promising antifungal vaccine candidates. 27624963 1 48 theme important 229:237 arg1 problem 246:252 this important health problem 224:252 this important health problem 224:252 With the rapid growth in fungal infections and drug-resistant fungal strains, antifungal vaccines have become an especially attractive strategy to tackle this important health problem. 27624963 3 49 theme β-1,3-glucan 463:474 arg1 branches 539:546 branches 539:546 branches at the 6-O-positions 539:567 β-Glucans have a conserved β-1,3-glucan backbone with sporadic β-1,3- or β-1,6-linked short glucans as branches at the 6-O-positions, and the branches may play a critical role in their immunologic functions. 27624963 3 49 theme β-1,3-glucan 463:474 arg1 backbone 476:483 a conserved β-1,3-glucan backbone 451:483 a conserved β-1,3-glucan backbone with sporadic β-1,3- or β-1,6-linked short glucans 451:534 β-Glucans have a conserved β-1,3-glucan backbone with sporadic β-1,3- or β-1,6-linked short glucans as branches at the 6-O-positions, and the branches may play a critical role in their immunologic functions. 27624963 9 50 theme protein 1705:1711 arg1 conjugates 1713:1722 the corresponding protein conjugates 1687:1722 the corresponding protein conjugates 1687:1722 Thus, branched oligo-β-glucans were identified as functional epitopes for antifungal vaccine design and the corresponding protein conjugates as promising antifungal vaccine candidates. 27624963 3 51 theme β-1,6-linked 509:520 arg1 glucans 528:534 β-1,6-linked short glucans 509:534 β-1,6-linked short glucans 509:534 β-Glucans have a conserved β-1,3-glucan backbone with sporadic β-1,3- or β-1,6-linked short glucans as branches at the 6-O-positions, and the branches may play a critical role in their immunologic functions. 27624963 4 52 theme structural 924:933 arg1 epitopes 935:942 the structural epitopes 920:942 the structural epitopes of natural β-glucans 920:963 To study the immunologic properties of branched β-glucans and develop β-glucan-based antifungal vaccines, three branched β-glucan oligosaccharides with 6-O-linked β-1,6-tetraglucose, β-1,3-diglucose, and β-1,3-tetraglucose branches on a β-1,3-nonaglucan backbone, which mimic the structural epitopes of natural β-glucans, were synthesized and coupled with keyhole limpet hemocyanin (KLH) to form novel synthetic conjugate vaccines. 27624963 1 53 theme health 239:244 arg1 problem 246:252 this important health problem 224:252 this important health problem 224:252 With the rapid growth in fungal infections and drug-resistant fungal strains, antifungal vaccines have become an especially attractive strategy to tackle this important health problem. 27624963 4 54 theme antifungal 729:738 arg1 vaccines 740:747 β-glucan-based antifungal vaccines 714:747 β-glucan-based antifungal vaccines 714:747 To study the immunologic properties of branched β-glucans and develop β-glucan-based antifungal vaccines, three branched β-glucan oligosaccharides with 6-O-linked β-1,6-tetraglucose, β-1,3-diglucose, and β-1,3-tetraglucose branches on a β-1,3-nonaglucan backbone, which mimic the structural epitopes of natural β-glucans, were synthesized and coupled with keyhole limpet hemocyanin (KLH) to form novel synthetic conjugate vaccines. 27624963 5 55 theme antibody 1131:1138 arg1 responses 1140:1148 strong IgG antibody responses 1120:1148 strong IgG antibody responses in mice 1120:1156 These glycoconjugates were proved to elicit strong IgG antibody responses in mice. 27624963 3 56 theme short 522:526 arg1 glucans 528:534 β-1,6-linked short glucans 509:534 β-1,6-linked short glucans 509:534 β-Glucans have a conserved β-1,3-glucan backbone with sporadic β-1,3- or β-1,6-linked short glucans as branches at the 6-O-positions, and the branches may play a critical role in their immunologic functions. 27624963 4 57 theme limpet 1008:1013 arg1 hemocyanin 1015:1024 keyhole limpet hemocyanin 1000:1024 keyhole limpet hemocyanin (KLH) 1000:1030 To study the immunologic properties of branched β-glucans and develop β-glucan-based antifungal vaccines, three branched β-glucan oligosaccharides with 6-O-linked β-1,6-tetraglucose, β-1,3-diglucose, and β-1,3-tetraglucose branches on a β-1,3-nonaglucan backbone, which mimic the structural epitopes of natural β-glucans, were synthesized and coupled with keyhole limpet hemocyanin (KLH) to form novel synthetic conjugate vaccines. 27624963 4 57 theme limpet 1008:1013 arg1 KLH 1027:1029 KLH 1027:1029 KLH 1027:1029 To study the immunologic properties of branched β-glucans and develop β-glucan-based antifungal vaccines, three branched β-glucan oligosaccharides with 6-O-linked β-1,6-tetraglucose, β-1,3-diglucose, and β-1,3-tetraglucose branches on a β-1,3-nonaglucan backbone, which mimic the structural epitopes of natural β-glucans, were synthesized and coupled with keyhole limpet hemocyanin (KLH) to form novel synthetic conjugate vaccines. 27624963 9 58 theme branched 1589:1596 arg1 candidates 1756:1765 promising antifungal vaccine candidates 1727:1765 promising antifungal vaccine candidates 1727:1765 Thus, branched oligo-β-glucans were identified as functional epitopes for antifungal vaccine design and the corresponding protein conjugates as promising antifungal vaccine candidates. 27624963 9 58 theme branched 1589:1596 arg1 epitopes 1644:1651 functional epitopes 1633:1651 functional epitopes for antifungal vaccine design and the corresponding protein conjugates 1633:1722 Thus, branched oligo-β-glucans were identified as functional epitopes for antifungal vaccine design and the corresponding protein conjugates as promising antifungal vaccine candidates. 27624963 9 58 theme branched 1589:1596 arg1 oligo-β-glucans 1598:1612 branched oligo-β-glucans 1589:1612 branched oligo-β-glucans 1589:1612 Thus, branched oligo-β-glucans were identified as functional epitopes for antifungal vaccine design and the corresponding protein conjugates as promising antifungal vaccine candidates. 27624963 2 59 theme intriguing 380:389 arg1 β-Glucans 255:263 β-Glucans 255:263 β-Glucans 255:263 β-Glucans, a class of extracellular carbohydrate antigens abundantly and consistently expressed on fungal cell surfaces, are intriguing epitopes for antifungal vaccine development. 27624963 2 59 theme intriguing 380:389 arg1 epitopes 391:398 intriguing epitopes 380:398 intriguing epitopes for antifungal vaccine development 380:433 β-Glucans, a class of extracellular carbohydrate antigens abundantly and consistently expressed on fungal cell surfaces, are intriguing epitopes for antifungal vaccine development. 27624963 3 60 theme conserved 453:461 arg1 branches 539:546 branches 539:546 branches at the 6-O-positions 539:567 β-Glucans have a conserved β-1,3-glucan backbone with sporadic β-1,3- or β-1,6-linked short glucans as branches at the 6-O-positions, and the branches may play a critical role in their immunologic functions. 27624963 3 60 theme conserved 453:461 arg1 backbone 476:483 a conserved β-1,3-glucan backbone 451:483 a conserved β-1,3-glucan backbone with sporadic β-1,3- or β-1,6-linked short glucans 451:534 β-Glucans have a conserved β-1,3-glucan backbone with sporadic β-1,3- or β-1,6-linked short glucans as branches at the 6-O-positions, and the branches may play a critical role in their immunologic functions. 27624963 4 61 theme keyhole 1000:1006 arg1 hemocyanin 1015:1024 keyhole limpet hemocyanin 1000:1024 keyhole limpet hemocyanin (KLH) 1000:1030 To study the immunologic properties of branched β-glucans and develop β-glucan-based antifungal vaccines, three branched β-glucan oligosaccharides with 6-O-linked β-1,6-tetraglucose, β-1,3-diglucose, and β-1,3-tetraglucose branches on a β-1,3-nonaglucan backbone, which mimic the structural epitopes of natural β-glucans, were synthesized and coupled with keyhole limpet hemocyanin (KLH) to form novel synthetic conjugate vaccines. 27624963 4 61 theme keyhole 1000:1006 arg1 KLH 1027:1029 KLH 1027:1029 KLH 1027:1029 To study the immunologic properties of branched β-glucans and develop β-glucan-based antifungal vaccines, three branched β-glucan oligosaccharides with 6-O-linked β-1,6-tetraglucose, β-1,3-diglucose, and β-1,3-tetraglucose branches on a β-1,3-nonaglucan backbone, which mimic the structural epitopes of natural β-glucans, were synthesized and coupled with keyhole limpet hemocyanin (KLH) to form novel synthetic conjugate vaccines. 27624963 8 62 theme Candida 1547:1553 arg1 albicans 1555:1562 Candida albicans 1547:1562 systemic Candida albicans infection in mice 1538:1580 Most importantly, these conjugates elicited effective protection against systemic Candida albicans infection in mice. 27624963 7 63 theme fungal 1451:1456 arg1 cells 1458:1462 natural β-glucans and fungal cells 1429:1462 natural β-glucans and fungal cells 1429:1462 Moreover, antibodies induced by the synthetic oligosaccharide-KLH conjugates were able to recognize and bind to natural β-glucans and fungal cells. 27624963 6 64 theme immunologic 1295:1305 arg1 property 1307:1314 the immunologic property 1291:1314 the immunologic property 1291:1314 It was also discovered that the number, size, and structure of branches linked to the β-glucan backbone had a significant impact on the immunologic property. 27624963 2 65 theme carbohydrate 291:302 arg1 antigens 304:311 extracellular carbohydrate antigens 277:311 extracellular carbohydrate antigens abundantly and consistently expressed on fungal cell surfaces 277:373 β-Glucans, a class of extracellular carbohydrate antigens abundantly and consistently expressed on fungal cell surfaces, are intriguing epitopes for antifungal vaccine development. 27624963 6 66 dep number 1191:1196 arg1 the 1187:1189 the 1187:1189 the 1187:1189 It was also discovered that the number, size, and structure of branches linked to the β-glucan backbone had a significant impact on the immunologic property. 27624963 1 67 theme antifungal 148:157 arg1 vaccines 159:166 antifungal vaccines 148:166 antifungal vaccines 148:166 With the rapid growth in fungal infections and drug-resistant fungal strains, antifungal vaccines have become an especially attractive strategy to tackle this important health problem. 27624963 4 68 theme β-1,3-tetraglucose 848:865 arg1 branches 867:874 6-O-linked β-1,6-tetraglucose, β-1,3-diglucose, and β-1,3-tetraglucose branches 796:874 6-O-linked β-1,6-tetraglucose, β-1,3-diglucose, and β-1,3-tetraglucose branches 796:874 To study the immunologic properties of branched β-glucans and develop β-glucan-based antifungal vaccines, three branched β-glucan oligosaccharides with 6-O-linked β-1,6-tetraglucose, β-1,3-diglucose, and β-1,3-tetraglucose branches on a β-1,3-nonaglucan backbone, which mimic the structural epitopes of natural β-glucans, were synthesized and coupled with keyhole limpet hemocyanin (KLH) to form novel synthetic conjugate vaccines. 27624963 4 69 theme immunologic 657:667 arg1 properties 669:678 the immunologic properties 653:678 the immunologic properties of branched β-glucans 653:700 To study the immunologic properties of branched β-glucans and develop β-glucan-based antifungal vaccines, three branched β-glucan oligosaccharides with 6-O-linked β-1,6-tetraglucose, β-1,3-diglucose, and β-1,3-tetraglucose branches on a β-1,3-nonaglucan backbone, which mimic the structural epitopes of natural β-glucans, were synthesized and coupled with keyhole limpet hemocyanin (KLH) to form novel synthetic conjugate vaccines. 27624963 2 70 theme antigens 304:311 arg1 β-Glucans 255:263 β-Glucans 255:263 β-Glucans 255:263 β-Glucans, a class of extracellular carbohydrate antigens abundantly and consistently expressed on fungal cell surfaces, are intriguing epitopes for antifungal vaccine development. 27624963 2 70 theme antigens 304:311 arg1 class 268:272 a class 266:272 a class of extracellular carbohydrate antigens abundantly and consistently expressed on fungal cell surfaces 266:373 β-Glucans, a class of extracellular carbohydrate antigens abundantly and consistently expressed on fungal cell surfaces, are intriguing epitopes for antifungal vaccine development. 27624963 2 71 theme extracellular 277:289 arg1 antigens 304:311 extracellular carbohydrate antigens 277:311 extracellular carbohydrate antigens abundantly and consistently expressed on fungal cell surfaces 277:373 β-Glucans, a class of extracellular carbohydrate antigens abundantly and consistently expressed on fungal cell surfaces, are intriguing epitopes for antifungal vaccine development. 27624963 4 72 theme β-1,6-tetraglucose 807:824 arg1 branches 867:874 6-O-linked β-1,6-tetraglucose, β-1,3-diglucose, and β-1,3-tetraglucose branches 796:874 6-O-linked β-1,6-tetraglucose, β-1,3-diglucose, and β-1,3-tetraglucose branches 796:874 To study the immunologic properties of branched β-glucans and develop β-glucan-based antifungal vaccines, three branched β-glucan oligosaccharides with 6-O-linked β-1,6-tetraglucose, β-1,3-diglucose, and β-1,3-tetraglucose branches on a β-1,3-nonaglucan backbone, which mimic the structural epitopes of natural β-glucans, were synthesized and coupled with keyhole limpet hemocyanin (KLH) to form novel synthetic conjugate vaccines. 27624963 6 73 theme branches 1222:1229 arg1 size 1199:1202 size 1199:1202 size 1199:1202 It was also discovered that the number, size, and structure of branches linked to the β-glucan backbone had a significant impact on the immunologic property. 27624963 6 73 theme branches 1222:1229 arg1 structure 1209:1217 structure 1209:1217 structure 1209:1217 It was also discovered that the number, size, and structure of branches linked to the β-glucan backbone had a significant impact on the immunologic property. 27624963 6 73 theme branches 1222:1229 arg1 number 1191:1196 number 1191:1196 number 1191:1196 It was also discovered that the number, size, and structure of branches linked to the β-glucan backbone had a significant impact on the immunologic property. 27624963 6 74 contain had 1263:1265 arg1 size 1199:1202 size 1199:1202 size 1199:1202 It was also discovered that the number, size, and structure of branches linked to the β-glucan backbone had a significant impact on the immunologic property. 27624963 6 74 contain had 1263:1265 arg2 impact 1281:1286 a significant impact 1267:1286 a significant impact 1267:1286 It was also discovered that the number, size, and structure of branches linked to the β-glucan backbone had a significant impact on the immunologic property. 27624963 6 74 contain had 1263:1265 arg1 number 1191:1196 number 1191:1196 number 1191:1196 It was also discovered that the number, size, and structure of branches linked to the β-glucan backbone had a significant impact on the immunologic property. 27624963 6 74 contain had 1263:1265 arg1 structure 1209:1217 structure 1209:1217 structure 1209:1217 It was also discovered that the number, size, and structure of branches linked to the β-glucan backbone had a significant impact on the immunologic property. 27624963 8 75 theme effective 1509:1517 arg1 protection 1519:1528 effective protection 1509:1528 effective protection against systemic Candida albicans infection in mice 1509:1580 Most importantly, these conjugates elicited effective protection against systemic Candida albicans infection in mice. 27624963 8 76 theme albicans 1555:1562 arg1 infection 1564:1572 systemic Candida albicans infection 1538:1572 systemic Candida albicans infection in mice 1538:1580 Most importantly, these conjugates elicited effective protection against systemic Candida albicans infection in mice. 27624963 2 77 theme vaccine 415:421 arg1 development 423:433 antifungal vaccine development 404:433 antifungal vaccine development 404:433 β-Glucans, a class of extracellular carbohydrate antigens abundantly and consistently expressed on fungal cell surfaces, are intriguing epitopes for antifungal vaccine development. 27624963 7 78 theme β-glucans 1437:1445 arg1 cells 1458:1462 natural β-glucans and fungal cells 1429:1462 natural β-glucans and fungal cells 1429:1462 Moreover, antibodies induced by the synthetic oligosaccharide-KLH conjugates were able to recognize and bind to natural β-glucans and fungal cells. 27624963 6 79 attach linked 1231:1236 arg2 branches 1222:1229 branches 1222:1229 branches linked to the β-glucan backbone 1222:1261 It was also discovered that the number, size, and structure of branches linked to the β-glucan backbone had a significant impact on the immunologic property. 27624963 6 79 attach linked 1231:1236 arg1 backbone 1254:1261 the β-glucan backbone 1241:1261 the β-glucan backbone 1241:1261 It was also discovered that the number, size, and structure of branches linked to the β-glucan backbone had a significant impact on the immunologic property. 27624963 9 80 theme functional 1633:1642 arg1 epitopes 1644:1651 functional epitopes 1633:1651 functional epitopes for antifungal vaccine design and the corresponding protein conjugates 1633:1722 Thus, branched oligo-β-glucans were identified as functional epitopes for antifungal vaccine design and the corresponding protein conjugates as promising antifungal vaccine candidates. 27624963 9 80 theme functional 1633:1642 arg1 oligo-β-glucans 1598:1612 branched oligo-β-glucans 1589:1612 branched oligo-β-glucans 1589:1612 Thus, branched oligo-β-glucans were identified as functional epitopes for antifungal vaccine design and the corresponding protein conjugates as promising antifungal vaccine candidates. 27624963 5 81 theme strong 1120:1125 arg1 responses 1140:1148 strong IgG antibody responses 1120:1148 strong IgG antibody responses in mice 1120:1156 These glycoconjugates were proved to elicit strong IgG antibody responses in mice. 27624963 7 82 theme synthetic 1353:1361 arg1 conjugates 1383:1392 the synthetic oligosaccharide-KLH conjugates 1349:1392 the synthetic oligosaccharide-KLH conjugates 1349:1392 Moreover, antibodies induced by the synthetic oligosaccharide-KLH conjugates were able to recognize and bind to natural β-glucans and fungal cells. 27624963 2 83 theme antifungal 404:413 arg1 development 423:433 antifungal vaccine development 404:433 antifungal vaccine development 404:433 β-Glucans, a class of extracellular carbohydrate antigens abundantly and consistently expressed on fungal cell surfaces, are intriguing epitopes for antifungal vaccine development. 27624963 4 84 from oligosaccharides 774:789 arg1 backbone 898:905 a β-1,3-nonaglucan backbone 879:905 a β-1,3-nonaglucan backbone 879:905 To study the immunologic properties of branched β-glucans and develop β-glucan-based antifungal vaccines, three branched β-glucan oligosaccharides with 6-O-linked β-1,6-tetraglucose, β-1,3-diglucose, and β-1,3-tetraglucose branches on a β-1,3-nonaglucan backbone, which mimic the structural epitopes of natural β-glucans, were synthesized and coupled with keyhole limpet hemocyanin (KLH) to form novel synthetic conjugate vaccines. 25133541 7 0 dep in 949:950 arg1 vitro 952:956 vitro 952:956 vitro 952:956 As a secreted protein, the protein level of OPN in the uterine cavity is enriched on day 4, and in vitro embryo culturing has indicated that OPN can facilitate blastocyst hatching and adhesion. 25133541 8 1 from adhesion 1079:1086 arg1 cells 1145:1149 mouse endometrial stromal cells 1119:1149 mouse endometrial stromal cells 1119:1149 Knockdown of OPN attenuates the adhesion and invasion of blastocysts in mouse endometrial stromal cells by suppressing the expression and enzymatic activity of matrix metalloproteinase-9 in the trophoblast. 25133541 2 2 theme cell 348:351 arg1 adhesion 353:360 cell adhesion 348:360 cell adhesion 348:360 Osteopontin (OPN) is a member of the small integrin-binding ligand N-linked glycoprotein family and participates in cell adhesion and invasion. 25133541 3 3 from sites 492:496 arg1 days 501:504 days 5 and 8 501:512 days 501:504 In this study, we showed that Opn mRNA levels are up-regulated in the mouse uterus on day 4 and at the implantation sites on days 5 and 8 of pregnancy. 25133541 3 3 from sites 492:496 arg1 8 512:512 8 512:512 8 512:512 In this study, we showed that Opn mRNA levels are up-regulated in the mouse uterus on day 4 and at the implantation sites on days 5 and 8 of pregnancy. 25133541 8 4 theme matrix 1207:1212 arg1 metalloproteinase-9 1214:1232 matrix metalloproteinase-9 1207:1232 matrix metalloproteinase-9 1207:1232 Knockdown of OPN attenuates the adhesion and invasion of blastocysts in mouse endometrial stromal cells by suppressing the expression and enzymatic activity of matrix metalloproteinase-9 in the trophoblast. 25133541 7 5 theme embryo 958:963 arg1 culturing 965:973 in vitro embryo culturing 949:973 in vitro embryo culturing 949:973 As a secreted protein, the protein level of OPN in the uterine cavity is enriched on day 4, and in vitro embryo culturing has indicated that OPN can facilitate blastocyst hatching and adhesion. 25133541 6 6 theme OPN 735:737 arg1 expression 739:748 OPN expression 735:748 OPN expression in the endometrial stromal cells 735:781 OPN expression in the endometrial stromal cells is regulated by progesterone, a key regulator during decidualization. 25133541 9 7 theme stroma 1437:1442 arg1 cells 1444:1448 mouse endometrial stroma cells 1419:1448 mouse endometrial stroma cells 1419:1448 Our data indicated that OPN expression in the mouse uterus during early pregnancy is essential for blastocyst hatching and adhesion and that the knockdown of OPN in mouse endometrial stroma cells could lead to a restrained in vitro trophoblast invasion. 25133541 9 8 theme early 1320:1324 arg1 pregnancy 1326:1334 early pregnancy 1320:1334 early pregnancy 1320:1334 Our data indicated that OPN expression in the mouse uterus during early pregnancy is essential for blastocyst hatching and adhesion and that the knockdown of OPN in mouse endometrial stroma cells could lead to a restrained in vitro trophoblast invasion. 25133541 0 9 theme blastocyst 87:96 arg1 attachment 98:107 mouse blastocyst attachment 81:107 mouse blastocyst attachment 81:107 Osteopontin is expressed in the mouse uterus during early pregnancy and promotes mouse blastocyst attachment and invasion in vitro. 25133541 6 10 theme key 815:817 arg1 regulator 819:827 a key regulator 813:827 a key regulator during decidualization 813:850 OPN expression in the endometrial stromal cells is regulated by progesterone, a key regulator during decidualization. 25133541 6 10 theme key 815:817 arg1 progesterone 799:810 progesterone 799:810 progesterone 799:810 OPN expression in the endometrial stromal cells is regulated by progesterone, a key regulator during decidualization. 25133541 7 11 theme protein 880:886 arg1 level 888:892 the protein level 876:892 the protein level of OPN in the uterine cavity 876:921 As a secreted protein, the protein level of OPN in the uterine cavity is enriched on day 4, and in vitro embryo culturing has indicated that OPN can facilitate blastocyst hatching and adhesion. 25133541 7 11 theme protein 880:886 arg1 protein 867:873 a secreted protein 856:873 a secreted protein 856:873 As a secreted protein, the protein level of OPN in the uterine cavity is enriched on day 4, and in vitro embryo culturing has indicated that OPN can facilitate blastocyst hatching and adhesion. 25133541 8 12 dep expression 1170:1179 arg1 the 1166:1168 the 1166:1168 the 1166:1168 Knockdown of OPN attenuates the adhesion and invasion of blastocysts in mouse endometrial stromal cells by suppressing the expression and enzymatic activity of matrix metalloproteinase-9 in the trophoblast. 25133541 0 13 theme mouse 81:85 arg1 attachment 98:107 mouse blastocyst attachment 81:107 mouse blastocyst attachment 81:107 Osteopontin is expressed in the mouse uterus during early pregnancy and promotes mouse blastocyst attachment and invasion in vitro. 25133541 4 14 theme pregnancy 649:657 arg1 day 640:642 day 8 640:644 day 8 of pregnancy 640:657 Immunohistochemistry localized the OPN protein to the glandular epithelium on day 4 and to the decidual zone on day 8 of pregnancy. 25133541 9 15 theme OPN 1412:1414 arg1 knockdown 1399:1407 the knockdown 1395:1407 the knockdown of OPN in mouse endometrial stroma cells 1395:1448 Our data indicated that OPN expression in the mouse uterus during early pregnancy is essential for blastocyst hatching and adhesion and that the knockdown of OPN in mouse endometrial stroma cells could lead to a restrained in vitro trophoblast invasion. 25133541 8 16 theme OPN 1060:1062 arg1 Knockdown 1047:1055 Knockdown 1047:1055 Knockdown of OPN 1047:1062 Knockdown of OPN attenuates the adhesion and invasion of blastocysts in mouse endometrial stromal cells by suppressing the expression and enzymatic activity of matrix metalloproteinase-9 in the trophoblast. 25133541 8 17 from expression 1170:1179 arg1 trophoblast 1241:1251 the trophoblast 1237:1251 the trophoblast 1237:1251 Knockdown of OPN attenuates the adhesion and invasion of blastocysts in mouse endometrial stromal cells by suppressing the expression and enzymatic activity of matrix metalloproteinase-9 in the trophoblast. 25133541 4 18 from zone 632:635 arg1 day 640:642 day 8 640:644 day 8 of pregnancy 640:657 Immunohistochemistry localized the OPN protein to the glandular epithelium on day 4 and to the decidual zone on day 8 of pregnancy. 25133541 3 19 theme implantation 479:490 arg1 sites 492:496 the implantation sites 475:496 the implantation sites on days 5 and 8 of pregnancy 475:525 In this study, we showed that Opn mRNA levels are up-regulated in the mouse uterus on day 4 and at the implantation sites on days 5 and 8 of pregnancy. 25133541 1 20 theme maternal 161:168 arg1 uterus 170:175 the maternal uterus 157:175 the maternal uterus 157:175 Embryo implantation into the maternal uterus is a decisive step for successful mammalian pregnancy. 25133541 8 21 theme blastocysts 1104:1114 arg1 adhesion 1079:1086 adhesion 1079:1086 adhesion 1079:1086 Knockdown of OPN attenuates the adhesion and invasion of blastocysts in mouse endometrial stromal cells by suppressing the expression and enzymatic activity of matrix metalloproteinase-9 in the trophoblast. 25133541 8 21 theme blastocysts 1104:1114 arg1 invasion 1092:1099 invasion 1092:1099 invasion 1092:1099 Knockdown of OPN attenuates the adhesion and invasion of blastocysts in mouse endometrial stromal cells by suppressing the expression and enzymatic activity of matrix metalloproteinase-9 in the trophoblast. 25133541 5 22 theme in 697:698 arg1 decidualization 718:732 in vivo and in vitro decidualization 697:732 in vivo and in vitro decidualization 697:732 OPN mRNA and proteins are induced by in vivo and in vitro decidualization. 25133541 8 23 theme mouse 1119:1123 arg1 cells 1145:1149 mouse endometrial stromal cells 1119:1149 mouse endometrial stromal cells 1119:1149 Knockdown of OPN attenuates the adhesion and invasion of blastocysts in mouse endometrial stromal cells by suppressing the expression and enzymatic activity of matrix metalloproteinase-9 in the trophoblast. 25133541 9 24 theme endometrial 1425:1435 arg1 cells 1444:1448 mouse endometrial stroma cells 1419:1448 mouse endometrial stroma cells 1419:1448 Our data indicated that OPN expression in the mouse uterus during early pregnancy is essential for blastocyst hatching and adhesion and that the knockdown of OPN in mouse endometrial stroma cells could lead to a restrained in vitro trophoblast invasion. 25133541 8 25 from invasion 1092:1099 arg1 cells 1145:1149 mouse endometrial stromal cells 1119:1149 mouse endometrial stromal cells 1119:1149 Knockdown of OPN attenuates the adhesion and invasion of blastocysts in mouse endometrial stromal cells by suppressing the expression and enzymatic activity of matrix metalloproteinase-9 in the trophoblast. 25133541 5 26 dep in 697:698 arg1 vivo 700:703 vivo 700:703 vivo 700:703 OPN mRNA and proteins are induced by in vivo and in vitro decidualization. 25133541 7 27 theme secreted 858:865 arg1 level 888:892 the protein level 876:892 the protein level of OPN in the uterine cavity 876:921 As a secreted protein, the protein level of OPN in the uterine cavity is enriched on day 4, and in vitro embryo culturing has indicated that OPN can facilitate blastocyst hatching and adhesion. 25133541 7 27 theme secreted 858:865 arg1 protein 867:873 a secreted protein 856:873 a secreted protein 856:873 As a secreted protein, the protein level of OPN in the uterine cavity is enriched on day 4, and in vitro embryo culturing has indicated that OPN can facilitate blastocyst hatching and adhesion. 25133541 2 28 theme N-linked 299:306 arg1 family 321:326 the small integrin-binding ligand N-linked glycoprotein family 265:326 the small integrin-binding ligand N-linked glycoprotein family 265:326 Osteopontin (OPN) is a member of the small integrin-binding ligand N-linked glycoprotein family and participates in cell adhesion and invasion. 25133541 9 29 theme blastocyst 1353:1362 arg1 hatching 1364:1371 blastocyst hatching 1353:1371 blastocyst hatching 1353:1371 Our data indicated that OPN expression in the mouse uterus during early pregnancy is essential for blastocyst hatching and adhesion and that the knockdown of OPN in mouse endometrial stroma cells could lead to a restrained in vitro trophoblast invasion. 25133541 8 30 theme endometrial 1125:1135 arg1 cells 1145:1149 mouse endometrial stromal cells 1119:1149 mouse endometrial stromal cells 1119:1149 Knockdown of OPN attenuates the adhesion and invasion of blastocysts in mouse endometrial stromal cells by suppressing the expression and enzymatic activity of matrix metalloproteinase-9 in the trophoblast. 25133541 9 31 theme OPN 1278:1280 arg1 expression 1282:1291 OPN expression 1278:1291 OPN expression in the mouse uterus during early pregnancy 1278:1334 Our data indicated that OPN expression in the mouse uterus during early pregnancy is essential for blastocyst hatching and adhesion and that the knockdown of OPN in mouse endometrial stroma cells could lead to a restrained in vitro trophoblast invasion. 25133541 2 32 theme ligand 292:297 arg1 family 321:326 the small integrin-binding ligand N-linked glycoprotein family 265:326 the small integrin-binding ligand N-linked glycoprotein family 265:326 Osteopontin (OPN) is a member of the small integrin-binding ligand N-linked glycoprotein family and participates in cell adhesion and invasion. 25133541 3 33 theme Opn 406:408 arg1 levels 415:420 Opn mRNA levels 406:420 Opn mRNA levels 406:420 In this study, we showed that Opn mRNA levels are up-regulated in the mouse uterus on day 4 and at the implantation sites on days 5 and 8 of pregnancy. 25133541 7 34 theme in 949:950 arg1 culturing 965:973 in vitro embryo culturing 949:973 in vitro embryo culturing 949:973 As a secreted protein, the protein level of OPN in the uterine cavity is enriched on day 4, and in vitro embryo culturing has indicated that OPN can facilitate blastocyst hatching and adhesion. 25133541 9 35 from knockdown 1399:1407 arg1 cells 1444:1448 mouse endometrial stroma cells 1419:1448 mouse endometrial stroma cells 1419:1448 Our data indicated that OPN expression in the mouse uterus during early pregnancy is essential for blastocyst hatching and adhesion and that the knockdown of OPN in mouse endometrial stroma cells could lead to a restrained in vitro trophoblast invasion. 25133541 2 36 theme integrin-binding 275:290 arg1 family 321:326 the small integrin-binding ligand N-linked glycoprotein family 265:326 the small integrin-binding ligand N-linked glycoprotein family 265:326 Osteopontin (OPN) is a member of the small integrin-binding ligand N-linked glycoprotein family and participates in cell adhesion and invasion. 25133541 4 37 from epithelium 592:601 arg1 day 606:608 day 4 606:610 day 4 606:610 Immunohistochemistry localized the OPN protein to the glandular epithelium on day 4 and to the decidual zone on day 8 of pregnancy. 25133541 1 38 theme decisive 182:189 arg1 step 191:194 a decisive step 180:194 a decisive step for successful mammalian pregnancy 180:229 Embryo implantation into the maternal uterus is a decisive step for successful mammalian pregnancy. 25133541 1 38 theme decisive 182:189 arg1 implantation 139:150 Embryo implantation 132:150 Embryo implantation into the maternal uterus 132:175 Embryo implantation into the maternal uterus is a decisive step for successful mammalian pregnancy. 25133541 9 39 theme restrained 1466:1475 arg1 invasion 1498:1505 a restrained in vitro trophoblast invasion 1464:1505 a restrained in vitro trophoblast invasion 1464:1505 Our data indicated that OPN expression in the mouse uterus during early pregnancy is essential for blastocyst hatching and adhesion and that the knockdown of OPN in mouse endometrial stroma cells could lead to a restrained in vitro trophoblast invasion. 25133541 2 40 theme small 269:273 arg1 family 321:326 the small integrin-binding ligand N-linked glycoprotein family 265:326 the small integrin-binding ligand N-linked glycoprotein family 265:326 Osteopontin (OPN) is a member of the small integrin-binding ligand N-linked glycoprotein family and participates in cell adhesion and invasion. 25133541 4 41 theme decidual 623:630 arg1 zone 632:635 the decidual zone 619:635 the decidual zone on day 8 of pregnancy 619:657 Immunohistochemistry localized the OPN protein to the glandular epithelium on day 4 and to the decidual zone on day 8 of pregnancy. 25133541 0 42 theme mouse 32:36 arg1 uterus 38:43 the mouse uterus 28:43 the mouse uterus 28:43 Osteopontin is expressed in the mouse uterus during early pregnancy and promotes mouse blastocyst attachment and invasion in vitro. 25133541 9 43 theme trophoblast 1486:1496 arg1 invasion 1498:1505 a restrained in vitro trophoblast invasion 1464:1505 a restrained in vitro trophoblast invasion 1464:1505 Our data indicated that OPN expression in the mouse uterus during early pregnancy is essential for blastocyst hatching and adhesion and that the knockdown of OPN in mouse endometrial stroma cells could lead to a restrained in vitro trophoblast invasion. 25133541 8 44 theme stromal 1137:1143 arg1 cells 1145:1149 mouse endometrial stromal cells 1119:1149 mouse endometrial stromal cells 1119:1149 Knockdown of OPN attenuates the adhesion and invasion of blastocysts in mouse endometrial stromal cells by suppressing the expression and enzymatic activity of matrix metalloproteinase-9 in the trophoblast. 25133541 7 45 from level 888:892 arg1 cavity 916:921 the uterine cavity 904:921 the uterine cavity 904:921 As a secreted protein, the protein level of OPN in the uterine cavity is enriched on day 4, and in vitro embryo culturing has indicated that OPN can facilitate blastocyst hatching and adhesion. 25133541 3 46 theme mRNA 410:413 arg1 levels 415:420 Opn mRNA levels 406:420 Opn mRNA levels 406:420 In this study, we showed that Opn mRNA levels are up-regulated in the mouse uterus on day 4 and at the implantation sites on days 5 and 8 of pregnancy. 25133541 6 47 from expression 739:748 arg1 cells 777:781 the endometrial stromal cells 753:781 the endometrial stromal cells 753:781 OPN expression in the endometrial stromal cells is regulated by progesterone, a key regulator during decidualization. 25133541 8 48 from activity 1195:1202 arg1 trophoblast 1241:1251 the trophoblast 1237:1251 the trophoblast 1237:1251 Knockdown of OPN attenuates the adhesion and invasion of blastocysts in mouse endometrial stromal cells by suppressing the expression and enzymatic activity of matrix metalloproteinase-9 in the trophoblast. 25133541 1 49 theme successful 200:209 arg1 pregnancy 221:229 successful mammalian pregnancy 200:229 successful mammalian pregnancy 200:229 Embryo implantation into the maternal uterus is a decisive step for successful mammalian pregnancy. 25133541 7 50 theme blastocyst 1013:1022 arg1 hatching 1024:1031 blastocyst hatching 1013:1031 blastocyst hatching 1013:1031 As a secreted protein, the protein level of OPN in the uterine cavity is enriched on day 4, and in vitro embryo culturing has indicated that OPN can facilitate blastocyst hatching and adhesion. 25133541 9 51 theme mouse 1419:1423 arg1 cells 1444:1448 mouse endometrial stroma cells 1419:1448 mouse endometrial stroma cells 1419:1448 Our data indicated that OPN expression in the mouse uterus during early pregnancy is essential for blastocyst hatching and adhesion and that the knockdown of OPN in mouse endometrial stroma cells could lead to a restrained in vitro trophoblast invasion. 25133541 6 52 theme stromal 769:775 arg1 cells 777:781 the endometrial stromal cells 753:781 the endometrial stromal cells 753:781 OPN expression in the endometrial stromal cells is regulated by progesterone, a key regulator during decidualization. 25133541 3 53 theme pregnancy 517:525 arg1 days 501:504 days 5 and 8 501:512 days 501:504 In this study, we showed that Opn mRNA levels are up-regulated in the mouse uterus on day 4 and at the implantation sites on days 5 and 8 of pregnancy. 25133541 9 54 from expression 1282:1291 arg1 uterus 1306:1311 the mouse uterus 1296:1311 the mouse uterus 1296:1311 Our data indicated that OPN expression in the mouse uterus during early pregnancy is essential for blastocyst hatching and adhesion and that the knockdown of OPN in mouse endometrial stroma cells could lead to a restrained in vitro trophoblast invasion. 25133541 8 55 theme enzymatic 1185:1193 arg1 activity 1195:1202 enzymatic activity 1185:1202 enzymatic activity 1185:1202 Knockdown of OPN attenuates the adhesion and invasion of blastocysts in mouse endometrial stromal cells by suppressing the expression and enzymatic activity of matrix metalloproteinase-9 in the trophoblast. 25133541 5 56 theme in 709:710 arg1 decidualization 718:732 in vivo and in vitro decidualization 697:732 in vivo and in vitro decidualization 697:732 OPN mRNA and proteins are induced by in vivo and in vitro decidualization. 25133541 2 57 link N-linked 299:306 arg1 family 321:326 the small integrin-binding ligand N-linked glycoprotein family 265:326 the small integrin-binding ligand N-linked glycoprotein family 265:326 Osteopontin (OPN) is a member of the small integrin-binding ligand N-linked glycoprotein family and participates in cell adhesion and invasion. 25133541 8 58 dep adhesion 1079:1086 arg1 the 1075:1077 the 1075:1077 the 1075:1077 Knockdown of OPN attenuates the adhesion and invasion of blastocysts in mouse endometrial stromal cells by suppressing the expression and enzymatic activity of matrix metalloproteinase-9 in the trophoblast. 25133541 6 59 theme endometrial 757:767 arg1 cells 777:781 the endometrial stromal cells 753:781 the endometrial stromal cells 753:781 OPN expression in the endometrial stromal cells is regulated by progesterone, a key regulator during decidualization. 25133541 5 60 dep in 709:710 arg1 vitro 712:716 vitro 712:716 vitro 712:716 OPN mRNA and proteins are induced by in vivo and in vitro decidualization. 25133541 2 61 gly glycoprotein 308:319 arg1 glycoprotein 308:319 the small integrin-binding ligand N-linked glycoprotein family 265:326 the small integrin-binding ligand N-linked glycoprotein family 265:326 Osteopontin (OPN) is a member of the small integrin-binding ligand N-linked glycoprotein family and participates in cell adhesion and invasion. 25133541 7 62 theme uterine 908:914 arg1 cavity 916:921 the uterine cavity 904:921 the uterine cavity 904:921 As a secreted protein, the protein level of OPN in the uterine cavity is enriched on day 4, and in vitro embryo culturing has indicated that OPN can facilitate blastocyst hatching and adhesion. 25133541 2 63 theme family 321:326 arg1 Osteopontin 232:242 Osteopontin 232:242 Osteopontin (OPN) 232:248 Osteopontin (OPN) is a member of the small integrin-binding ligand N-linked glycoprotein family and participates in cell adhesion and invasion. 25133541 2 63 theme family 321:326 arg1 member 255:260 a member 253:260 a member of the small integrin-binding ligand N-linked glycoprotein family 253:326 Osteopontin (OPN) is a member of the small integrin-binding ligand N-linked glycoprotein family and participates in cell adhesion and invasion. 25133541 9 64 theme in 1477:1478 arg1 invasion 1498:1505 a restrained in vitro trophoblast invasion 1464:1505 a restrained in vitro trophoblast invasion 1464:1505 Our data indicated that OPN expression in the mouse uterus during early pregnancy is essential for blastocyst hatching and adhesion and that the knockdown of OPN in mouse endometrial stroma cells could lead to a restrained in vitro trophoblast invasion. 25133541 1 65 theme mammalian 211:219 arg1 pregnancy 221:229 successful mammalian pregnancy 200:229 successful mammalian pregnancy 200:229 Embryo implantation into the maternal uterus is a decisive step for successful mammalian pregnancy. 25133541 8 66 theme metalloproteinase-9 1214:1232 arg1 activity 1195:1202 enzymatic activity 1185:1202 enzymatic activity 1185:1202 Knockdown of OPN attenuates the adhesion and invasion of blastocysts in mouse endometrial stromal cells by suppressing the expression and enzymatic activity of matrix metalloproteinase-9 in the trophoblast. 25133541 8 66 theme metalloproteinase-9 1214:1232 arg1 expression 1170:1179 expression 1170:1179 expression 1170:1179 Knockdown of OPN attenuates the adhesion and invasion of blastocysts in mouse endometrial stromal cells by suppressing the expression and enzymatic activity of matrix metalloproteinase-9 in the trophoblast. 25133541 7 67 theme OPN 897:899 arg1 level 888:892 the protein level 876:892 the protein level of OPN in the uterine cavity 876:921 As a secreted protein, the protein level of OPN in the uterine cavity is enriched on day 4, and in vitro embryo culturing has indicated that OPN can facilitate blastocyst hatching and adhesion. 25133541 7 67 theme OPN 897:899 arg1 protein 867:873 a secreted protein 856:873 a secreted protein 856:873 As a secreted protein, the protein level of OPN in the uterine cavity is enriched on day 4, and in vitro embryo culturing has indicated that OPN can facilitate blastocyst hatching and adhesion. 25133541 2 68 theme glycoprotein 308:319 arg1 family 321:326 the small integrin-binding ligand N-linked glycoprotein family 265:326 the small integrin-binding ligand N-linked glycoprotein family 265:326 Osteopontin (OPN) is a member of the small integrin-binding ligand N-linked glycoprotein family and participates in cell adhesion and invasion. 25133541 3 69 theme mouse 446:450 arg1 uterus 452:457 the mouse uterus 442:457 the mouse uterus 442:457 In this study, we showed that Opn mRNA levels are up-regulated in the mouse uterus on day 4 and at the implantation sites on days 5 and 8 of pregnancy. 25133541 9 70 dep in 1477:1478 arg1 vitro 1480:1484 vitro 1480:1484 vitro 1480:1484 Our data indicated that OPN expression in the mouse uterus during early pregnancy is essential for blastocyst hatching and adhesion and that the knockdown of OPN in mouse endometrial stroma cells could lead to a restrained in vitro trophoblast invasion. 25133541 4 71 theme glandular 582:590 arg1 epithelium 592:601 the glandular epithelium 578:601 the glandular epithelium on day 4 578:610 Immunohistochemistry localized the OPN protein to the glandular epithelium on day 4 and to the decidual zone on day 8 of pregnancy. 25133541 1 72 theme Embryo 132:137 arg1 implantation 139:150 Embryo implantation 132:150 Embryo implantation into the maternal uterus 132:175 Embryo implantation into the maternal uterus is a decisive step for successful mammalian pregnancy. 25133541 1 72 theme Embryo 132:137 arg1 step 191:194 a decisive step 180:194 a decisive step for successful mammalian pregnancy 180:229 Embryo implantation into the maternal uterus is a decisive step for successful mammalian pregnancy. 25133541 9 73 theme mouse 1300:1304 arg1 uterus 1306:1311 the mouse uterus 1296:1311 the mouse uterus 1296:1311 Our data indicated that OPN expression in the mouse uterus during early pregnancy is essential for blastocyst hatching and adhesion and that the knockdown of OPN in mouse endometrial stroma cells could lead to a restrained in vitro trophoblast invasion. 25133541 0 74 theme early 52:56 arg1 pregnancy 58:66 early pregnancy 52:66 early pregnancy 52:66 Osteopontin is expressed in the mouse uterus during early pregnancy and promotes mouse blastocyst attachment and invasion in vitro. 25133541 4 75 theme OPN 563:565 arg1 protein 567:573 the OPN protein 559:573 the OPN protein 559:573 Immunohistochemistry localized the OPN protein to the glandular epithelium on day 4 and to the decidual zone on day 8 of pregnancy. 25133541 5 76 theme OPN 660:662 arg1 mRNA 664:667 OPN mRNA 660:667 OPN mRNA 660:667 OPN mRNA and proteins are induced by in vivo and in vitro decidualization. 24333479 7 0 theme novel 1059:1063 arg1 algorithms 1085:1094 novel data representation algorithms 1059:1094 novel data representation algorithms with feature selection and multiple kernel learning 1059:1146 By optimizing the objective functions iteratively, we develop novel data representation algorithms with feature selection and multiple kernel learning respectively. 24333479 5 1 theme feature 776:782 arg1 selection 784:792 feature selection 776:792 feature selection 776:792 To overcome this problem, we integrate feature selection and multiple kernel learning into the sparse coding on the manifold. 24333479 1 2 theme representation 152:165 arg1 representation 92:105 Sparse representation 85:105 Sparse representation 85:105 Sparse representation has been widely studied as a part-based data representation method and applied in many scientific and engineering fields, such as bioinformatics and medical imaging. 24333479 1 2 theme representation 152:165 arg1 method 167:172 a part-based data representation method 134:172 a part-based data representation method 134:172 Sparse representation has been widely studied as a part-based data representation method and applied in many scientific and engineering fields, such as bioinformatics and medical imaging. 24333479 4 3 theme nonlinear 533:541 arg1 distribution 543:554 nonlinear distribution 533:554 nonlinear distribution 533:554 However, due to the noisy features and nonlinear distribution of the data samples, the affinity graph constructed directly from the original feature space is not necessarily a reliable reflection of the intrinsic manifold of the data samples. 24333479 8 4 theme proposed 1289:1296 arg1 algorithms 1298:1307 the proposed algorithms 1285:1307 the proposed algorithms 1285:1307 Experimental results on two challenging tasks, N-linked glycosylation prediction and mammogram retrieval, demonstrate that the proposed algorithms outperform the traditional sparse coding methods. 24333479 0 5 from selection 8:16 arg1 manifold 75:82 manifold 75:82 manifold 75:82 Feature selection and multi-kernel learning for sparse representation on a manifold. 24333479 7 6 theme data 1065:1068 arg1 algorithms 1085:1094 novel data representation algorithms 1059:1094 novel data representation algorithms with feature selection and multiple kernel learning 1059:1146 By optimizing the objective functions iteratively, we develop novel data representation algorithms with feature selection and multiple kernel learning respectively. 24333479 1 7 theme medical 256:262 arg1 imaging 264:270 medical imaging 256:270 medical imaging 256:270 Sparse representation has been widely studied as a part-based data representation method and applied in many scientific and engineering fields, such as bioinformatics and medical imaging. 24333479 3 8 theme affinity 478:485 arg1 graph 487:491 an affinity graph 475:491 an affinity graph 475:491 Gao et al. (2013) recently proposed Laplacian sparse coding by regularizing the sparse codes with an affinity graph. 24333479 8 9 theme sparse 1336:1341 arg1 methods 1350:1356 the traditional sparse coding methods 1320:1356 the traditional sparse coding methods 1320:1356 Experimental results on two challenging tasks, N-linked glycosylation prediction and mammogram retrieval, demonstrate that the proposed algorithms outperform the traditional sparse coding methods. 24333479 4 10 dep features 520:527 arg1 the 510:512 the 510:512 the 510:512 However, due to the noisy features and nonlinear distribution of the data samples, the affinity graph constructed directly from the original feature space is not necessarily a reliable reflection of the intrinsic manifold of the data samples. 24333479 8 11 theme traditional 1324:1334 arg1 methods 1350:1356 the traditional sparse coding methods 1320:1356 the traditional sparse coding methods 1320:1356 Experimental results on two challenging tasks, N-linked glycosylation prediction and mammogram retrieval, demonstrate that the proposed algorithms outperform the traditional sparse coding methods. 24333479 2 12 from combination 328:338 arg1 dictionary 365:374 a dictionary 363:374 a dictionary 363:374 It seeks to represent a data sample as a sparse linear combination of some basic items in a dictionary. 24333479 7 13 with algorithms 1085:1094 arg1 learning 1139:1146 multiple kernel learning 1123:1146 multiple kernel learning 1123:1146 By optimizing the objective functions iteratively, we develop novel data representation algorithms with feature selection and multiple kernel learning respectively. 24333479 7 13 with algorithms 1085:1094 arg1 selection 1109:1117 feature selection 1101:1117 feature selection 1101:1117 By optimizing the objective functions iteratively, we develop novel data representation algorithms with feature selection and multiple kernel learning respectively. 24333479 4 14 theme reliable 670:677 arg1 graph 590:594 the affinity graph 577:594 the affinity graph constructed directly from the original feature space 577:647 However, due to the noisy features and nonlinear distribution of the data samples, the affinity graph constructed directly from the original feature space is not necessarily a reliable reflection of the intrinsic manifold of the data samples. 24333479 4 14 theme reliable 670:677 arg1 reflection 679:688 a reliable reflection 668:688 a reliable reflection of the intrinsic manifold of the data samples 668:734 However, due to the noisy features and nonlinear distribution of the data samples, the affinity graph constructed directly from the original feature space is not necessarily a reliable reflection of the intrinsic manifold of the data samples. 24333479 3 15 dep Gao 377:379 arg1 et al 381:385 et al 381:385 Gao et al. (2013) 377:393 Gao et al. (2013) recently proposed Laplacian sparse coding by regularizing the sparse codes with an affinity graph. 24333479 5 16 from coding 839:844 arg1 manifold 853:860 manifold 853:860 manifold 853:860 To overcome this problem, we integrate feature selection and multiple kernel learning into the sparse coding on the manifold. 24333479 3 17 dep sparse 457:462 arg1 codes 464:468 codes 464:468 codes 464:468 Gao et al. (2013) recently proposed Laplacian sparse coding by regularizing the sparse codes with an affinity graph. 24333479 8 18 theme glycosylation 1218:1230 arg1 tasks 1202:1206 two challenging tasks 1186:1206 two challenging tasks 1186:1206 Experimental results on two challenging tasks, N-linked glycosylation prediction and mammogram retrieval, demonstrate that the proposed algorithms outperform the traditional sparse coding methods. 24333479 8 18 theme glycosylation 1218:1230 arg1 prediction 1232:1241 N-linked glycosylation prediction 1209:1241 N-linked glycosylation prediction 1209:1241 Experimental results on two challenging tasks, N-linked glycosylation prediction and mammogram retrieval, demonstrate that the proposed algorithms outperform the traditional sparse coding methods. 24333479 5 19 theme kernel 807:812 arg1 learning 814:821 multiple kernel learning 798:821 multiple kernel learning 798:821 To overcome this problem, we integrate feature selection and multiple kernel learning into the sparse coding on the manifold. 24333479 6 20 theme kernel 939:944 arg1 learning 946:953 multiple kernel learning 930:953 multiple kernel learning 930:953 To this end, unified objectives are defined for feature selection, multiple kernel learning, sparse coding, and graph regularization. 24333479 4 21 theme data 723:726 arg1 samples 728:734 the data samples 719:734 the data samples 719:734 However, due to the noisy features and nonlinear distribution of the data samples, the affinity graph constructed directly from the original feature space is not necessarily a reliable reflection of the intrinsic manifold of the data samples. 24333479 7 22 theme kernel 1132:1137 arg1 learning 1139:1146 multiple kernel learning 1123:1146 multiple kernel learning 1123:1146 By optimizing the objective functions iteratively, we develop novel data representation algorithms with feature selection and multiple kernel learning respectively. 24333479 7 23 theme multiple 1123:1130 arg1 learning 1139:1146 multiple kernel learning 1123:1146 multiple kernel learning 1123:1146 By optimizing the objective functions iteratively, we develop novel data representation algorithms with feature selection and multiple kernel learning respectively. 24333479 0 24 from learning 35:42 arg1 manifold 75:82 manifold 75:82 manifold 75:82 Feature selection and multi-kernel learning for sparse representation on a manifold. 24333479 7 25 theme objective 1015:1023 arg1 functions 1025:1033 the objective functions 1011:1033 the objective functions iteratively 1011:1045 By optimizing the objective functions iteratively, we develop novel data representation algorithms with feature selection and multiple kernel learning respectively. 24333479 1 26 theme Sparse 85:90 arg1 representation 92:105 Sparse representation 85:105 Sparse representation 85:105 Sparse representation has been widely studied as a part-based data representation method and applied in many scientific and engineering fields, such as bioinformatics and medical imaging. 24333479 1 26 theme Sparse 85:90 arg1 method 167:172 a part-based data representation method 134:172 a part-based data representation method 134:172 Sparse representation has been widely studied as a part-based data representation method and applied in many scientific and engineering fields, such as bioinformatics and medical imaging. 24333479 4 27 theme original 626:633 arg1 space 643:647 the original feature space 622:647 the original feature space 622:647 However, due to the noisy features and nonlinear distribution of the data samples, the affinity graph constructed directly from the original feature space is not necessarily a reliable reflection of the intrinsic manifold of the data samples. 24333479 0 28 theme Feature 0:6 arg1 selection 8:16 Feature selection 0:16 Feature selection 0:16 Feature selection and multi-kernel learning for sparse representation on a manifold. 24333479 6 29 theme feature 911:917 arg1 selection 919:927 feature selection 911:927 feature selection 911:927 To this end, unified objectives are defined for feature selection, multiple kernel learning, sparse coding, and graph regularization. 24333479 2 30 from items 354:358 arg1 dictionary 365:374 a dictionary 363:374 a dictionary 363:374 It seeks to represent a data sample as a sparse linear combination of some basic items in a dictionary. 24333479 1 31 theme many 189:192 arg1 bioinformatics 237:250 bioinformatics 237:250 bioinformatics 237:250 Sparse representation has been widely studied as a part-based data representation method and applied in many scientific and engineering fields, such as bioinformatics and medical imaging. 24333479 1 31 theme many 189:192 arg1 imaging 264:270 medical imaging 256:270 medical imaging 256:270 Sparse representation has been widely studied as a part-based data representation method and applied in many scientific and engineering fields, such as bioinformatics and medical imaging. 24333479 1 31 theme many 189:192 arg1 fields 221:226 many scientific and engineering fields 189:226 many scientific and engineering fields 189:226 Sparse representation has been widely studied as a part-based data representation method and applied in many scientific and engineering fields, such as bioinformatics and medical imaging. 24333479 0 32 theme multi-kernel 22:33 arg1 learning 35:42 multi-kernel learning 22:42 multi-kernel learning 22:42 Feature selection and multi-kernel learning for sparse representation on a manifold. 24333479 8 33 link N-linked 1209:1216 arg1 tasks 1202:1206 two challenging tasks 1186:1206 two challenging tasks 1186:1206 Experimental results on two challenging tasks, N-linked glycosylation prediction and mammogram retrieval, demonstrate that the proposed algorithms outperform the traditional sparse coding methods. 24333479 8 33 link N-linked 1209:1216 arg1 prediction 1232:1241 N-linked glycosylation prediction 1209:1241 N-linked glycosylation prediction 1209:1241 Experimental results on two challenging tasks, N-linked glycosylation prediction and mammogram retrieval, demonstrate that the proposed algorithms outperform the traditional sparse coding methods. 24333479 2 34 theme data 297:300 arg1 combination 328:338 a sparse linear combination 312:338 a sparse linear combination of some basic items in a dictionary 312:374 It seeks to represent a data sample as a sparse linear combination of some basic items in a dictionary. 24333479 2 34 theme data 297:300 arg1 sample 302:307 a data sample 295:307 a data sample 295:307 It seeks to represent a data sample as a sparse linear combination of some basic items in a dictionary. 24333479 1 35 theme scientific 194:203 arg1 bioinformatics 237:250 bioinformatics 237:250 bioinformatics 237:250 Sparse representation has been widely studied as a part-based data representation method and applied in many scientific and engineering fields, such as bioinformatics and medical imaging. 24333479 1 35 theme scientific 194:203 arg1 imaging 264:270 medical imaging 256:270 medical imaging 256:270 Sparse representation has been widely studied as a part-based data representation method and applied in many scientific and engineering fields, such as bioinformatics and medical imaging. 24333479 1 35 theme scientific 194:203 arg1 fields 221:226 many scientific and engineering fields 189:226 many scientific and engineering fields 189:226 Sparse representation has been widely studied as a part-based data representation method and applied in many scientific and engineering fields, such as bioinformatics and medical imaging. 24333479 4 36 theme samples 728:734 arg1 manifold 707:714 manifold 707:714 manifold 707:714 However, due to the noisy features and nonlinear distribution of the data samples, the affinity graph constructed directly from the original feature space is not necessarily a reliable reflection of the intrinsic manifold of the data samples. 24333479 1 37 theme part-based 136:145 arg1 representation 92:105 Sparse representation 85:105 Sparse representation 85:105 Sparse representation has been widely studied as a part-based data representation method and applied in many scientific and engineering fields, such as bioinformatics and medical imaging. 24333479 1 37 theme part-based 136:145 arg1 method 167:172 a part-based data representation method 134:172 a part-based data representation method 134:172 Sparse representation has been widely studied as a part-based data representation method and applied in many scientific and engineering fields, such as bioinformatics and medical imaging. 24333479 4 38 theme noisy 514:518 arg1 features 520:527 noisy features 514:527 noisy features 514:527 However, due to the noisy features and nonlinear distribution of the data samples, the affinity graph constructed directly from the original feature space is not necessarily a reliable reflection of the intrinsic manifold of the data samples. 24333479 1 39 theme engineering 209:219 arg1 bioinformatics 237:250 bioinformatics 237:250 bioinformatics 237:250 Sparse representation has been widely studied as a part-based data representation method and applied in many scientific and engineering fields, such as bioinformatics and medical imaging. 24333479 1 39 theme engineering 209:219 arg1 imaging 264:270 medical imaging 256:270 medical imaging 256:270 Sparse representation has been widely studied as a part-based data representation method and applied in many scientific and engineering fields, such as bioinformatics and medical imaging. 24333479 1 39 theme engineering 209:219 arg1 fields 221:226 many scientific and engineering fields 189:226 many scientific and engineering fields 189:226 Sparse representation has been widely studied as a part-based data representation method and applied in many scientific and engineering fields, such as bioinformatics and medical imaging. 24333479 8 40 theme N-linked 1209:1216 arg1 tasks 1202:1206 two challenging tasks 1186:1206 two challenging tasks 1186:1206 Experimental results on two challenging tasks, N-linked glycosylation prediction and mammogram retrieval, demonstrate that the proposed algorithms outperform the traditional sparse coding methods. 24333479 8 40 theme N-linked 1209:1216 arg1 prediction 1232:1241 N-linked glycosylation prediction 1209:1241 N-linked glycosylation prediction 1209:1241 Experimental results on two challenging tasks, N-linked glycosylation prediction and mammogram retrieval, demonstrate that the proposed algorithms outperform the traditional sparse coding methods. 24333479 3 41 theme Laplacian 413:421 arg1 sparse 423:428 Laplacian sparse 413:428 Laplacian sparse coding by regularizing the sparse codes with an affinity graph 413:491 Gao et al. (2013) recently proposed Laplacian sparse coding by regularizing the sparse codes with an affinity graph. 24333479 7 42 theme feature 1101:1107 arg1 selection 1109:1117 feature selection 1101:1117 feature selection 1101:1117 By optimizing the objective functions iteratively, we develop novel data representation algorithms with feature selection and multiple kernel learning respectively. 24333479 6 43 theme multiple 930:937 arg1 learning 946:953 multiple kernel learning 930:953 multiple kernel learning 930:953 To this end, unified objectives are defined for feature selection, multiple kernel learning, sparse coding, and graph regularization. 24333479 8 44 theme Experimental 1162:1173 arg1 results 1175:1181 Experimental results 1162:1181 Experimental results on two challenging tasks, N-linked glycosylation prediction and mammogram retrieval, 1162:1266 Experimental results on two challenging tasks, N-linked glycosylation prediction and mammogram retrieval, demonstrate that the proposed algorithms outperform the traditional sparse coding methods. 24333479 6 45 theme graph 975:979 arg1 regularization 981:994 graph regularization 975:994 graph regularization 975:994 To this end, unified objectives are defined for feature selection, multiple kernel learning, sparse coding, and graph regularization. 24333479 5 46 theme multiple 798:805 arg1 learning 814:821 multiple kernel learning 798:821 multiple kernel learning 798:821 To overcome this problem, we integrate feature selection and multiple kernel learning into the sparse coding on the manifold. 24333479 7 47 theme representation 1070:1083 arg1 algorithms 1085:1094 novel data representation algorithms 1059:1094 novel data representation algorithms with feature selection and multiple kernel learning 1059:1146 By optimizing the objective functions iteratively, we develop novel data representation algorithms with feature selection and multiple kernel learning respectively. 24333479 5 48 theme sparse 832:837 arg1 coding 839:844 the sparse coding 828:844 the sparse coding on the manifold 828:860 To overcome this problem, we integrate feature selection and multiple kernel learning into the sparse coding on the manifold. 24333479 0 49 theme sparse 48:53 arg1 representation 55:68 sparse representation 48:68 sparse representation 48:68 Feature selection and multi-kernel learning for sparse representation on a manifold. 24333479 8 50 from results 1175:1181 arg1 tasks 1202:1206 two challenging tasks 1186:1206 two challenging tasks 1186:1206 Experimental results on two challenging tasks, N-linked glycosylation prediction and mammogram retrieval, demonstrate that the proposed algorithms outperform the traditional sparse coding methods. 24333479 8 50 from results 1175:1181 arg1 prediction 1232:1241 N-linked glycosylation prediction 1209:1241 N-linked glycosylation prediction 1209:1241 Experimental results on two challenging tasks, N-linked glycosylation prediction and mammogram retrieval, demonstrate that the proposed algorithms outperform the traditional sparse coding methods. 24333479 8 50 from results 1175:1181 arg1 retrieval 1257:1265 mammogram retrieval 1247:1265 mammogram retrieval 1247:1265 Experimental results on two challenging tasks, N-linked glycosylation prediction and mammogram retrieval, demonstrate that the proposed algorithms outperform the traditional sparse coding methods. 24333479 2 51 theme linear 321:326 arg1 combination 328:338 a sparse linear combination 312:338 a sparse linear combination of some basic items in a dictionary 312:374 It seeks to represent a data sample as a sparse linear combination of some basic items in a dictionary. 24333479 2 51 theme linear 321:326 arg1 sample 302:307 a data sample 295:307 a data sample 295:307 It seeks to represent a data sample as a sparse linear combination of some basic items in a dictionary. 24333479 2 52 from dictionary 365:374 arg1 combination 328:338 a sparse linear combination 312:338 a sparse linear combination of some basic items in a dictionary 312:374 It seeks to represent a data sample as a sparse linear combination of some basic items in a dictionary. 24333479 2 52 from dictionary 365:374 arg1 sample 302:307 a data sample 295:307 a data sample 295:307 It seeks to represent a data sample as a sparse linear combination of some basic items in a dictionary. 24333479 2 53 theme sparse 314:319 arg1 combination 328:338 a sparse linear combination 312:338 a sparse linear combination of some basic items in a dictionary 312:374 It seeks to represent a data sample as a sparse linear combination of some basic items in a dictionary. 24333479 2 53 theme sparse 314:319 arg1 sample 302:307 a data sample 295:307 a data sample 295:307 It seeks to represent a data sample as a sparse linear combination of some basic items in a dictionary. 24333479 4 54 theme manifold 707:714 arg1 graph 590:594 the affinity graph 577:594 the affinity graph constructed directly from the original feature space 577:647 However, due to the noisy features and nonlinear distribution of the data samples, the affinity graph constructed directly from the original feature space is not necessarily a reliable reflection of the intrinsic manifold of the data samples. 24333479 4 54 theme manifold 707:714 arg1 reflection 679:688 a reliable reflection 668:688 a reliable reflection of the intrinsic manifold of the data samples 668:734 However, due to the noisy features and nonlinear distribution of the data samples, the affinity graph constructed directly from the original feature space is not necessarily a reliable reflection of the intrinsic manifold of the data samples. 24333479 4 55 theme data 563:566 arg1 samples 568:574 the data samples 559:574 the data samples 559:574 However, due to the noisy features and nonlinear distribution of the data samples, the affinity graph constructed directly from the original feature space is not necessarily a reliable reflection of the intrinsic manifold of the data samples. 24333479 8 56 theme coding 1343:1348 arg1 methods 1350:1356 the traditional sparse coding methods 1320:1356 the traditional sparse coding methods 1320:1356 Experimental results on two challenging tasks, N-linked glycosylation prediction and mammogram retrieval, demonstrate that the proposed algorithms outperform the traditional sparse coding methods. 24333479 1 57 theme data 147:150 arg1 representation 92:105 Sparse representation 85:105 Sparse representation 85:105 Sparse representation has been widely studied as a part-based data representation method and applied in many scientific and engineering fields, such as bioinformatics and medical imaging. 24333479 1 57 theme data 147:150 arg1 method 167:172 a part-based data representation method 134:172 a part-based data representation method 134:172 Sparse representation has been widely studied as a part-based data representation method and applied in many scientific and engineering fields, such as bioinformatics and medical imaging. 24333479 6 58 theme sparse 956:961 arg1 coding 963:968 sparse coding 956:968 sparse coding 956:968 To this end, unified objectives are defined for feature selection, multiple kernel learning, sparse coding, and graph regularization. 24333479 4 59 theme feature 635:641 arg1 space 643:647 the original feature space 622:647 the original feature space 622:647 However, due to the noisy features and nonlinear distribution of the data samples, the affinity graph constructed directly from the original feature space is not necessarily a reliable reflection of the intrinsic manifold of the data samples. 24333479 8 60 theme mammogram 1247:1255 arg1 tasks 1202:1206 two challenging tasks 1186:1206 two challenging tasks 1186:1206 Experimental results on two challenging tasks, N-linked glycosylation prediction and mammogram retrieval, demonstrate that the proposed algorithms outperform the traditional sparse coding methods. 24333479 8 60 theme mammogram 1247:1255 arg1 retrieval 1257:1265 mammogram retrieval 1247:1265 mammogram retrieval 1247:1265 Experimental results on two challenging tasks, N-linked glycosylation prediction and mammogram retrieval, demonstrate that the proposed algorithms outperform the traditional sparse coding methods. 24333479 4 61 theme affinity 581:588 arg1 graph 590:594 the affinity graph 577:594 the affinity graph constructed directly from the original feature space 577:647 However, due to the noisy features and nonlinear distribution of the data samples, the affinity graph constructed directly from the original feature space is not necessarily a reliable reflection of the intrinsic manifold of the data samples. 24333479 4 61 theme affinity 581:588 arg1 reflection 679:688 a reliable reflection 668:688 a reliable reflection of the intrinsic manifold of the data samples 668:734 However, due to the noisy features and nonlinear distribution of the data samples, the affinity graph constructed directly from the original feature space is not necessarily a reliable reflection of the intrinsic manifold of the data samples. 24333479 2 62 theme items 354:358 arg1 combination 328:338 a sparse linear combination 312:338 a sparse linear combination of some basic items in a dictionary 312:374 It seeks to represent a data sample as a sparse linear combination of some basic items in a dictionary. 24333479 2 62 theme items 354:358 arg1 sample 302:307 a data sample 295:307 a data sample 295:307 It seeks to represent a data sample as a sparse linear combination of some basic items in a dictionary. 24333479 8 63 theme challenging 1190:1200 arg1 tasks 1202:1206 two challenging tasks 1186:1206 two challenging tasks 1186:1206 Experimental results on two challenging tasks, N-linked glycosylation prediction and mammogram retrieval, demonstrate that the proposed algorithms outperform the traditional sparse coding methods. 24333479 8 63 theme challenging 1190:1200 arg1 prediction 1232:1241 N-linked glycosylation prediction 1209:1241 N-linked glycosylation prediction 1209:1241 Experimental results on two challenging tasks, N-linked glycosylation prediction and mammogram retrieval, demonstrate that the proposed algorithms outperform the traditional sparse coding methods. 24333479 8 63 theme challenging 1190:1200 arg1 retrieval 1257:1265 mammogram retrieval 1247:1265 mammogram retrieval 1247:1265 Experimental results on two challenging tasks, N-linked glycosylation prediction and mammogram retrieval, demonstrate that the proposed algorithms outperform the traditional sparse coding methods. 24333479 2 64 theme basic 348:352 arg1 items 354:358 some basic items 343:358 some basic items in a dictionary 343:374 It seeks to represent a data sample as a sparse linear combination of some basic items in a dictionary. 24333479 6 65 theme unified 876:882 arg1 objectives 884:893 unified objectives 876:893 unified objectives 876:893 To this end, unified objectives are defined for feature selection, multiple kernel learning, sparse coding, and graph regularization. 24333479 4 66 theme samples 568:574 arg1 distribution 543:554 nonlinear distribution 533:554 nonlinear distribution 533:554 However, due to the noisy features and nonlinear distribution of the data samples, the affinity graph constructed directly from the original feature space is not necessarily a reliable reflection of the intrinsic manifold of the data samples. 24333479 4 66 theme samples 568:574 arg1 features 520:527 noisy features 514:527 noisy features 514:527 However, due to the noisy features and nonlinear distribution of the data samples, the affinity graph constructed directly from the original feature space is not necessarily a reliable reflection of the intrinsic manifold of the data samples. 28245984 6 0 theme absorptions 825:835 arg1 spectrum 802:809 the spectrum 798:809 the spectrum of these main absorptions 798:835 In infarcted myocardium, the spectrum of these main absorptions was deeply altered. 28245984 12 1 from association 1669:1679 arg1 evolution 1624:1632 a profound evolution 1613:1632 a profound evolution of protein secondary structures in association with collagen deposition and reorganization of water involved in the scar maturation of peri- and infarct zones post-MI 1613:1799 In conclusion, our results indicate a profound evolution of protein secondary structures in association with collagen deposition and reorganization of water involved in the scar maturation of peri- and infarct zones post-MI. 28245984 10 2 theme deep 1367:1370 arg1 increase 1372:1379 a deep increase 1365:1379 a deep increase of unfreezable water/freezable water in peri- and infarcted tissues 1365:1447 Thermal analysis indicates a deep increase of unfreezable water/freezable water in peri- and infarcted tissues. 28245984 2 3 theme MI 311:312 arg1 sites 314:318 MI sites 311:318 MI sites 311:318 Histopathological characterization is commonly used to detect the location, size and shape of MI sites. 28245984 5 4 from proteins 714:721 arg1 tissue 738:743 freeze-died tissue 726:743 freeze-died tissue as major absorptions bands 726:770 The FTIR spectra of healthy and remote myocardial tissue shows amides A, I, II and III associated with proteins in freeze-died tissue as major absorptions bands. 28245984 12 5 from structures 1655:1664 arg1 association 1669:1679 association 1669:1679 association with collagen deposition 1669:1704 In conclusion, our results indicate a profound evolution of protein secondary structures in association with collagen deposition and reorganization of water involved in the scar maturation of peri- and infarct zones post-MI. 28245984 7 6 from 1338cm-1 973:980 arg1 feature 921:927 the distinct feature 908:927 the distinct feature of the collagen specific absorption band at 1338cm-1 in the infarct area at 21days post-MI 908:1018 FITR evidenced an increase of the amide A band and the distinct feature of the collagen specific absorption band at 1338cm-1 in the infarct area at 21days post-MI. 28245984 7 6 from 1338cm-1 973:980 arg1 post-MI 1012:1018 21days post-MI 1005:1018 21days post-MI 1005:1018 FITR evidenced an increase of the amide A band and the distinct feature of the collagen specific absorption band at 1338cm-1 in the infarct area at 21days post-MI. 28245984 7 6 from 1338cm-1 973:980 arg1 band 965:968 the collagen specific absorption band 932:968 the collagen specific absorption band at 1338cm-1 in the infarct area at 21days post-MI 932:1018 FITR evidenced an increase of the amide A band and the distinct feature of the collagen specific absorption band at 1338cm-1 in the infarct area at 21days post-MI. 28245984 7 6 from 1338cm-1 973:980 arg1 area 997:1000 the infarct area 985:1000 the infarct area at 21days post-MI 985:1018 FITR evidenced an increase of the amide A band and the distinct feature of the collagen specific absorption band at 1338cm-1 in the infarct area at 21days post-MI. 28245984 7 6 from 1338cm-1 973:980 arg1 increase 875:882 an increase 872:882 an increase of the amide A band 872:902 FITR evidenced an increase of the amide A band and the distinct feature of the collagen specific absorption band at 1338cm-1 in the infarct area at 21days post-MI. 28245984 5 7 theme tissue 661:666 arg1 spectra 620:626 The FTIR spectra 611:626 The FTIR spectra of healthy and remote myocardial tissue 611:666 The FTIR spectra of healthy and remote myocardial tissue shows amides A, I, II and III associated with proteins in freeze-died tissue as major absorptions bands. 28245984 11 8 theme new 1562:1564 arg1 structure 1566:1574 a new structure 1560:1574 a new structure 1560:1574 In infarcted tissue is evidenced the impairment of myofibrillar proteins thermal profile and the emergence of a new structure. 28245984 1 9 theme heart 202:206 arg1 failure 208:214 heart failure 202:214 heart failure 202:214 Adverse cardiac remodeling after myocardial infarction (MI) causes impaired ventricular function and heart failure. 28245984 8 10 theme helical 1157:1163 arg1 conformation 1165:1176 the triple helical conformation 1146:1176 the triple helical conformation 1146:1176 At 21days post-MI, it also appears an important shift of amide I from 1646cm-1 to 1637cm-1 that suggests the predominance of the triple helical conformation in the proteins. 28245984 10 11 theme water/freezable 1396:1410 arg1 water 1412:1416 unfreezable water/freezable water 1384:1416 unfreezable water/freezable water 1384:1416 Thermal analysis indicates a deep increase of unfreezable water/freezable water in peri- and infarcted tissues. 28245984 9 12 from carbohydrates 1273:1285 arg1 polysaccharides 1303:1317 polysaccharides 1303:1317 polysaccharides 1303:1317 The new spectra bands also indicate an increase in proteoglycans, residues of carbohydrates in proteins and polysaccharides in ischemic areas. 28245984 9 12 from carbohydrates 1273:1285 arg1 proteins 1290:1297 proteins 1290:1297 proteins 1290:1297 The new spectra bands also indicate an increase in proteoglycans, residues of carbohydrates in proteins and polysaccharides in ischemic areas. 28245984 12 13 theme scar 1750:1753 arg1 maturation 1755:1764 the scar maturation 1746:1764 the scar maturation of peri- and infarct zones post-MI 1746:1799 In conclusion, our results indicate a profound evolution of protein secondary structures in association with collagen deposition and reorganization of water involved in the scar maturation of peri- and infarct zones post-MI. 28245984 12 14 from evolution 1624:1632 arg1 association 1669:1679 association 1669:1679 association with collagen deposition 1669:1704 In conclusion, our results indicate a profound evolution of protein secondary structures in association with collagen deposition and reorganization of water involved in the scar maturation of peri- and infarct zones post-MI. 28245984 9 15 theme new 1199:1201 arg1 spectra 1203:1209 The new spectra 1195:1209 The new spectra bands 1195:1215 The new spectra bands also indicate an increase in proteoglycans, residues of carbohydrates in proteins and polysaccharides in ischemic areas. 28245984 9 16 from residues 1261:1268 arg1 polysaccharides 1303:1317 polysaccharides 1303:1317 polysaccharides 1303:1317 The new spectra bands also indicate an increase in proteoglycans, residues of carbohydrates in proteins and polysaccharides in ischemic areas. 28245984 9 16 from residues 1261:1268 arg1 proteins 1290:1297 proteins 1290:1297 proteins 1290:1297 The new spectra bands also indicate an increase in proteoglycans, residues of carbohydrates in proteins and polysaccharides in ischemic areas. 28245984 5 17 theme freeze-died 726:736 arg1 tissue 738:743 freeze-died tissue 726:743 freeze-died tissue as major absorptions bands 726:770 The FTIR spectra of healthy and remote myocardial tissue shows amides A, I, II and III associated with proteins in freeze-died tissue as major absorptions bands. 28245984 7 18 theme 21days 1005:1010 arg1 post-MI 1012:1018 21days post-MI 1005:1018 21days post-MI 1005:1018 FITR evidenced an increase of the amide A band and the distinct feature of the collagen specific absorption band at 1338cm-1 in the infarct area at 21days post-MI. 28245984 7 19 from feature 921:927 arg1 1338cm-1 973:980 1338cm-1 973:980 1338cm-1 in the infarct area at 21days post-MI 973:1018 FITR evidenced an increase of the amide A band and the distinct feature of the collagen specific absorption band at 1338cm-1 in the infarct area at 21days post-MI. 28245984 3 20 theme chemical 352:359 arg1 composition 361:371 chemical composition 352:371 chemical composition 352:371 However, the information about chemical composition, physical structure and molecular mobility of peri- and infarct zones post-MI is rather limited. 28245984 0 21 theme post-myocardial 73:87 arg1 infarction 89:98 left ventricle remodeling post-myocardial infarction 47:98 left ventricle remodeling post-myocardial infarction 47:98 Conformational and thermal characterization of left ventricle remodeling post-myocardial infarction. 28245984 1 22 theme impaired 168:175 arg1 function 189:196 impaired ventricular function 168:196 impaired ventricular function 168:196 Adverse cardiac remodeling after myocardial infarction (MI) causes impaired ventricular function and heart failure. 28245984 12 23 theme collagen 1686:1693 arg1 deposition 1695:1704 collagen deposition 1686:1704 collagen deposition 1686:1704 In conclusion, our results indicate a profound evolution of protein secondary structures in association with collagen deposition and reorganization of water involved in the scar maturation of peri- and infarct zones post-MI. 28245984 11 24 theme thermal 1523:1529 arg1 profile 1531:1537 thermal profile 1523:1537 thermal profile 1523:1537 In infarcted tissue is evidenced the impairment of myofibrillar proteins thermal profile and the emergence of a new structure. 28245984 11 24 theme thermal 1523:1529 arg1 proteins 1514:1521 myofibrillar proteins 1501:1521 myofibrillar proteins thermal profile and the emergence of a new structure 1501:1574 In infarcted tissue is evidenced the impairment of myofibrillar proteins thermal profile and the emergence of a new structure. 28245984 7 25 theme band 965:968 arg1 feature 921:927 the distinct feature 908:927 the distinct feature of the collagen specific absorption band at 1338cm-1 in the infarct area at 21days post-MI 908:1018 FITR evidenced an increase of the amide A band and the distinct feature of the collagen specific absorption band at 1338cm-1 in the infarct area at 21days post-MI. 28245984 7 25 theme band 965:968 arg1 increase 875:882 an increase 872:882 an increase of the amide A band 872:902 FITR evidenced an increase of the amide A band and the distinct feature of the collagen specific absorption band at 1338cm-1 in the infarct area at 21days post-MI. 28245984 4 26 theme spatiotemporal 521:534 arg1 alterations 564:574 the spatiotemporal biochemical and biophysical alterations 517:574 the spatiotemporal biochemical and biophysical alterations of key cardiac components 517:600 The main objective of this work was to explore the spatiotemporal biochemical and biophysical alterations of key cardiac components post-MI. 28245984 11 27 theme myofibrillar 1501:1512 arg1 profile 1531:1537 thermal profile 1523:1537 thermal profile 1523:1537 In infarcted tissue is evidenced the impairment of myofibrillar proteins thermal profile and the emergence of a new structure. 28245984 11 27 theme myofibrillar 1501:1512 arg1 emergence 1547:1555 the emergence 1543:1555 the emergence of a new structure 1543:1574 In infarcted tissue is evidenced the impairment of myofibrillar proteins thermal profile and the emergence of a new structure. 28245984 11 27 theme myofibrillar 1501:1512 arg1 proteins 1514:1521 myofibrillar proteins 1501:1521 myofibrillar proteins thermal profile and the emergence of a new structure 1501:1574 In infarcted tissue is evidenced the impairment of myofibrillar proteins thermal profile and the emergence of a new structure. 28245984 9 28 theme carbohydrates 1273:1285 arg1 residues 1261:1268 residues 1261:1268 residues of carbohydrates in proteins and polysaccharides in ischemic areas 1261:1335 The new spectra bands also indicate an increase in proteoglycans, residues of carbohydrates in proteins and polysaccharides in ischemic areas. 28245984 9 28 theme carbohydrates 1273:1285 arg1 proteoglycans 1246:1258 proteoglycans 1246:1258 proteoglycans 1246:1258 The new spectra bands also indicate an increase in proteoglycans, residues of carbohydrates in proteins and polysaccharides in ischemic areas. 28245984 9 28 theme carbohydrates 1273:1285 arg1 carbohydrates 1273:1285 carbohydrates 1273:1285 carbohydrates in proteins and polysaccharides in ischemic areas 1273:1335 The new spectra bands also indicate an increase in proteoglycans, residues of carbohydrates in proteins and polysaccharides in ischemic areas. 28245984 8 29 theme 21days 1024:1029 arg1 post-MI 1031:1037 21days post-MI 1024:1037 21days post-MI 1024:1037 At 21days post-MI, it also appears an important shift of amide I from 1646cm-1 to 1637cm-1 that suggests the predominance of the triple helical conformation in the proteins. 28245984 7 30 theme specific 945:952 arg1 band 965:968 the collagen specific absorption band 932:968 the collagen specific absorption band at 1338cm-1 in the infarct area at 21days post-MI 932:1018 FITR evidenced an increase of the amide A band and the distinct feature of the collagen specific absorption band at 1338cm-1 in the infarct area at 21days post-MI. 28245984 12 31 theme structures 1655:1664 arg1 evolution 1624:1632 a profound evolution 1613:1632 a profound evolution of protein secondary structures in association with collagen deposition and reorganization of water involved in the scar maturation of peri- and infarct zones post-MI 1613:1799 In conclusion, our results indicate a profound evolution of protein secondary structures in association with collagen deposition and reorganization of water involved in the scar maturation of peri- and infarct zones post-MI. 28245984 5 32 theme absorptions 754:764 arg1 bands 766:770 major absorptions bands 748:770 major absorptions bands 748:770 The FTIR spectra of healthy and remote myocardial tissue shows amides A, I, II and III associated with proteins in freeze-died tissue as major absorptions bands. 28245984 1 33 theme Adverse 101:107 arg1 remodeling 117:126 Adverse cardiac remodeling 101:126 Adverse cardiac remodeling after myocardial infarction (MI) 101:159 Adverse cardiac remodeling after myocardial infarction (MI) causes impaired ventricular function and heart failure. 28245984 0 34 theme Conformational 0:13 arg1 characterization 27:42 Conformational and thermal characterization 0:42 Conformational and thermal characterization of left ventricle remodeling post-myocardial infarction. 0:99 Conformational and thermal characterization of left ventricle remodeling post-myocardial infarction. 28245984 5 35 theme FTIR 615:618 arg1 spectra 620:626 The FTIR spectra 611:626 The FTIR spectra of healthy and remote myocardial tissue 611:666 The FTIR spectra of healthy and remote myocardial tissue shows amides A, I, II and III associated with proteins in freeze-died tissue as major absorptions bands. 28245984 3 36 theme molecular 397:405 arg1 mobility 407:414 molecular mobility 397:414 molecular mobility 397:414 However, the information about chemical composition, physical structure and molecular mobility of peri- and infarct zones post-MI is rather limited. 28245984 4 37 theme key 579:581 arg1 components 591:600 key cardiac components 579:600 key cardiac components 579:600 The main objective of this work was to explore the spatiotemporal biochemical and biophysical alterations of key cardiac components post-MI. 28245984 0 38 theme thermal 19:25 arg1 characterization 27:42 Conformational and thermal characterization 0:42 Conformational and thermal characterization of left ventricle remodeling post-myocardial infarction. 0:99 Conformational and thermal characterization of left ventricle remodeling post-myocardial infarction. 28245984 9 39 theme ischemic 1322:1329 arg1 areas 1331:1335 ischemic areas 1322:1335 ischemic areas 1322:1335 The new spectra bands also indicate an increase in proteoglycans, residues of carbohydrates in proteins and polysaccharides in ischemic areas. 28245984 1 40 theme myocardial 134:143 arg1 MI 157:158 MI 157:158 MI 157:158 Adverse cardiac remodeling after myocardial infarction (MI) causes impaired ventricular function and heart failure. 28245984 1 40 theme myocardial 134:143 arg1 infarction 145:154 myocardial infarction 134:154 myocardial infarction (MI) 134:159 Adverse cardiac remodeling after myocardial infarction (MI) causes impaired ventricular function and heart failure. 28245984 12 41 theme protein 1637:1643 arg1 structures 1655:1664 protein secondary structures 1637:1664 protein secondary structures in association with collagen deposition 1637:1704 In conclusion, our results indicate a profound evolution of protein secondary structures in association with collagen deposition and reorganization of water involved in the scar maturation of peri- and infarct zones post-MI. 28245984 4 42 theme components 591:600 arg1 alterations 564:574 the spatiotemporal biochemical and biophysical alterations 517:574 the spatiotemporal biochemical and biophysical alterations of key cardiac components 517:600 The main objective of this work was to explore the spatiotemporal biochemical and biophysical alterations of key cardiac components post-MI. 28245984 10 43 dep peri- 1421:1425 arg1 tissues 1441:1447 tissues 1441:1447 tissues 1441:1447 Thermal analysis indicates a deep increase of unfreezable water/freezable water in peri- and infarcted tissues. 28245984 0 44 theme ventricle 52:60 arg1 infarction 89:98 left ventricle remodeling post-myocardial infarction 47:98 left ventricle remodeling post-myocardial infarction 47:98 Conformational and thermal characterization of left ventricle remodeling post-myocardial infarction. 28245984 8 45 theme amide 1078:1082 arg1 shift 1069:1073 an important shift 1056:1073 an important shift of amide I from 1646cm-1 to 1637cm-1 that suggests the predominance of the triple helical conformation in the proteins 1056:1192 At 21days post-MI, it also appears an important shift of amide I from 1646cm-1 to 1637cm-1 that suggests the predominance of the triple helical conformation in the proteins. 28245984 7 46 theme distinct 912:919 arg1 feature 921:927 the distinct feature 908:927 the distinct feature of the collagen specific absorption band at 1338cm-1 in the infarct area at 21days post-MI 908:1018 FITR evidenced an increase of the amide A band and the distinct feature of the collagen specific absorption band at 1338cm-1 in the infarct area at 21days post-MI. 28245984 8 47 from predominance 1130:1141 arg1 proteins 1185:1192 the proteins 1181:1192 the proteins 1181:1192 At 21days post-MI, it also appears an important shift of amide I from 1646cm-1 to 1637cm-1 that suggests the predominance of the triple helical conformation in the proteins. 28245984 12 48 theme post-MI 1793:1799 arg1 maturation 1755:1764 the scar maturation 1746:1764 the scar maturation of peri- and infarct zones post-MI 1746:1799 In conclusion, our results indicate a profound evolution of protein secondary structures in association with collagen deposition and reorganization of water involved in the scar maturation of peri- and infarct zones post-MI. 28245984 10 49 from increase 1372:1379 arg1 infarcted 1431:1439 infarcted 1431:1439 infarcted 1431:1439 Thermal analysis indicates a deep increase of unfreezable water/freezable water in peri- and infarcted tissues. 28245984 10 49 from increase 1372:1379 arg1 peri- 1421:1425 peri- 1421:1425 peri- 1421:1425 Thermal analysis indicates a deep increase of unfreezable water/freezable water in peri- and infarcted tissues. 28245984 2 50 theme Histopathological 217:233 arg1 characterization 235:250 Histopathological characterization 217:250 Histopathological characterization 217:250 Histopathological characterization is commonly used to detect the location, size and shape of MI sites. 28245984 9 51 from proteins 1290:1297 arg1 residues 1261:1268 residues 1261:1268 residues of carbohydrates in proteins and polysaccharides in ischemic areas 1261:1335 The new spectra bands also indicate an increase in proteoglycans, residues of carbohydrates in proteins and polysaccharides in ischemic areas. 28245984 9 51 from proteins 1290:1297 arg1 proteoglycans 1246:1258 proteoglycans 1246:1258 proteoglycans 1246:1258 The new spectra bands also indicate an increase in proteoglycans, residues of carbohydrates in proteins and polysaccharides in ischemic areas. 28245984 9 51 from proteins 1290:1297 arg1 areas 1331:1335 ischemic areas 1322:1335 ischemic areas 1322:1335 The new spectra bands also indicate an increase in proteoglycans, residues of carbohydrates in proteins and polysaccharides in ischemic areas. 28245984 9 51 from proteins 1290:1297 arg1 carbohydrates 1273:1285 carbohydrates 1273:1285 carbohydrates in proteins and polysaccharides in ischemic areas 1273:1335 The new spectra bands also indicate an increase in proteoglycans, residues of carbohydrates in proteins and polysaccharides in ischemic areas. 28245984 9 52 dep spectra 1203:1209 arg1 bands 1211:1215 bands 1211:1215 The new spectra bands 1195:1215 The new spectra bands also indicate an increase in proteoglycans, residues of carbohydrates in proteins and polysaccharides in ischemic areas. 28245984 7 53 theme A 897:897 arg1 band 899:902 the amide A band 887:902 the amide A band 887:902 FITR evidenced an increase of the amide A band and the distinct feature of the collagen specific absorption band at 1338cm-1 in the infarct area at 21days post-MI. 28245984 12 54 theme peri- 1769:1773 arg1 maturation 1755:1764 the scar maturation 1746:1764 the scar maturation of peri- and infarct zones post-MI 1746:1799 In conclusion, our results indicate a profound evolution of protein secondary structures in association with collagen deposition and reorganization of water involved in the scar maturation of peri- and infarct zones post-MI. 28245984 10 55 theme water 1412:1416 arg1 increase 1372:1379 a deep increase 1365:1379 a deep increase of unfreezable water/freezable water in peri- and infarcted tissues 1365:1447 Thermal analysis indicates a deep increase of unfreezable water/freezable water in peri- and infarcted tissues. 28245984 6 56 theme main 820:823 arg1 absorptions 825:835 these main absorptions 814:835 these main absorptions 814:835 In infarcted myocardium, the spectrum of these main absorptions was deeply altered. 28245984 2 57 theme sites 314:318 arg1 shape 302:306 shape 302:306 shape 302:306 Histopathological characterization is commonly used to detect the location, size and shape of MI sites. 28245984 2 57 theme sites 314:318 arg1 size 293:296 size 293:296 size 293:296 Histopathological characterization is commonly used to detect the location, size and shape of MI sites. 28245984 2 57 theme sites 314:318 arg1 location 283:290 location 283:290 location 283:290 Histopathological characterization is commonly used to detect the location, size and shape of MI sites. 28245984 12 58 theme infarct 1779:1785 arg1 post-MI 1793:1799 infarct zones post-MI 1779:1799 infarct zones post-MI 1779:1799 In conclusion, our results indicate a profound evolution of protein secondary structures in association with collagen deposition and reorganization of water involved in the scar maturation of peri- and infarct zones post-MI. 28245984 5 59 theme myocardial 650:659 arg1 tissue 661:666 healthy and remote myocardial tissue 631:666 healthy and remote myocardial tissue 631:666 The FTIR spectra of healthy and remote myocardial tissue shows amides A, I, II and III associated with proteins in freeze-died tissue as major absorptions bands. 28245984 11 60 theme structure 1566:1574 arg1 profile 1531:1537 thermal profile 1523:1537 thermal profile 1523:1537 In infarcted tissue is evidenced the impairment of myofibrillar proteins thermal profile and the emergence of a new structure. 28245984 11 60 theme structure 1566:1574 arg1 emergence 1547:1555 the emergence 1543:1555 the emergence of a new structure 1543:1574 In infarcted tissue is evidenced the impairment of myofibrillar proteins thermal profile and the emergence of a new structure. 28245984 11 60 theme structure 1566:1574 arg1 proteins 1514:1521 myofibrillar proteins 1501:1521 myofibrillar proteins thermal profile and the emergence of a new structure 1501:1574 In infarcted tissue is evidenced the impairment of myofibrillar proteins thermal profile and the emergence of a new structure. 28245984 8 61 theme triple 1150:1155 arg1 conformation 1165:1176 the triple helical conformation 1146:1176 the triple helical conformation 1146:1176 At 21days post-MI, it also appears an important shift of amide I from 1646cm-1 to 1637cm-1 that suggests the predominance of the triple helical conformation in the proteins. 28245984 8 62 attach predominance 1130:1141 arg1 proteins 1185:1192 the proteins 1181:1192 the proteins 1181:1192 At 21days post-MI, it also appears an important shift of amide I from 1646cm-1 to 1637cm-1 that suggests the predominance of the triple helical conformation in the proteins. 28245984 8 62 attach predominance 1130:1141 arg2 conformation 1165:1176 the triple helical conformation 1146:1176 the triple helical conformation 1146:1176 At 21days post-MI, it also appears an important shift of amide I from 1646cm-1 to 1637cm-1 that suggests the predominance of the triple helical conformation in the proteins. 28245984 2 63 used used 264:267 arg2 characterization 235:250 Histopathological characterization 217:250 Histopathological characterization 217:250 Histopathological characterization is commonly used to detect the location, size and shape of MI sites. 28245984 10 64 theme unfreezable 1384:1394 arg1 water 1412:1416 unfreezable water/freezable water 1384:1416 unfreezable water/freezable water 1384:1416 Thermal analysis indicates a deep increase of unfreezable water/freezable water in peri- and infarcted tissues. 28245984 8 65 theme conformation 1165:1176 arg1 predominance 1130:1141 the predominance 1126:1141 the predominance of the triple helical conformation in the proteins 1126:1192 At 21days post-MI, it also appears an important shift of amide I from 1646cm-1 to 1637cm-1 that suggests the predominance of the triple helical conformation in the proteins. 28245984 4 66 theme main 474:477 arg1 objective 479:487 The main objective 470:487 The main objective of this work 470:500 The main objective of this work was to explore the spatiotemporal biochemical and biophysical alterations of key cardiac components post-MI. 28245984 7 67 from post-MI 1012:1018 arg1 1338cm-1 973:980 1338cm-1 973:980 1338cm-1 in the infarct area at 21days post-MI 973:1018 FITR evidenced an increase of the amide A band and the distinct feature of the collagen specific absorption band at 1338cm-1 in the infarct area at 21days post-MI. 28245984 7 67 from post-MI 1012:1018 arg1 area 997:1000 the infarct area 985:1000 the infarct area at 21days post-MI 985:1018 FITR evidenced an increase of the amide A band and the distinct feature of the collagen specific absorption band at 1338cm-1 in the infarct area at 21days post-MI. 28245984 12 68 from reorganization 1710:1723 arg1 association 1669:1679 association 1669:1679 association with collagen deposition 1669:1704 In conclusion, our results indicate a profound evolution of protein secondary structures in association with collagen deposition and reorganization of water involved in the scar maturation of peri- and infarct zones post-MI. 28245984 12 69 theme reorganization 1710:1723 arg1 evolution 1624:1632 a profound evolution 1613:1632 a profound evolution of protein secondary structures in association with collagen deposition and reorganization of water involved in the scar maturation of peri- and infarct zones post-MI 1613:1799 In conclusion, our results indicate a profound evolution of protein secondary structures in association with collagen deposition and reorganization of water involved in the scar maturation of peri- and infarct zones post-MI. 28245984 0 70 theme infarction 89:98 arg1 characterization 27:42 Conformational and thermal characterization 0:42 Conformational and thermal characterization of left ventricle remodeling post-myocardial infarction. 0:99 Conformational and thermal characterization of left ventricle remodeling post-myocardial infarction. 28245984 7 71 theme infarct 989:995 arg1 area 997:1000 the infarct area 985:1000 the infarct area at 21days post-MI 985:1018 FITR evidenced an increase of the amide A band and the distinct feature of the collagen specific absorption band at 1338cm-1 in the infarct area at 21days post-MI. 28245984 12 72 theme water 1728:1732 arg1 structures 1655:1664 protein secondary structures 1637:1664 protein secondary structures in association with collagen deposition 1637:1704 In conclusion, our results indicate a profound evolution of protein secondary structures in association with collagen deposition and reorganization of water involved in the scar maturation of peri- and infarct zones post-MI. 28245984 12 72 theme water 1728:1732 arg1 reorganization 1710:1723 reorganization 1710:1723 reorganization of water involved in the scar maturation of peri- and infarct zones post-MI 1710:1799 In conclusion, our results indicate a profound evolution of protein secondary structures in association with collagen deposition and reorganization of water involved in the scar maturation of peri- and infarct zones post-MI. 28245984 11 73 theme proteins 1514:1521 arg1 impairment 1487:1496 the impairment 1483:1496 the impairment of myofibrillar proteins thermal profile and the emergence of a new structure 1483:1574 In infarcted tissue is evidenced the impairment of myofibrillar proteins thermal profile and the emergence of a new structure. 28245984 1 74 theme ventricular 177:187 arg1 function 189:196 impaired ventricular function 168:196 impaired ventricular function 168:196 Adverse cardiac remodeling after myocardial infarction (MI) causes impaired ventricular function and heart failure. 28245984 8 75 from 1646cm-1 1091:1098 arg1 shift 1069:1073 an important shift 1056:1073 an important shift of amide I from 1646cm-1 to 1637cm-1 that suggests the predominance of the triple helical conformation in the proteins 1056:1192 At 21days post-MI, it also appears an important shift of amide I from 1646cm-1 to 1637cm-1 that suggests the predominance of the triple helical conformation in the proteins. 28245984 4 76 theme biochemical 536:546 arg1 alterations 564:574 the spatiotemporal biochemical and biophysical alterations 517:574 the spatiotemporal biochemical and biophysical alterations of key cardiac components 517:600 The main objective of this work was to explore the spatiotemporal biochemical and biophysical alterations of key cardiac components post-MI. 28245984 5 77 theme healthy 631:637 arg1 tissue 661:666 healthy and remote myocardial tissue 631:666 healthy and remote myocardial tissue 631:666 The FTIR spectra of healthy and remote myocardial tissue shows amides A, I, II and III associated with proteins in freeze-died tissue as major absorptions bands. 28245984 4 78 theme work 497:500 arg1 objective 479:487 The main objective 470:487 The main objective of this work 470:500 The main objective of this work was to explore the spatiotemporal biochemical and biophysical alterations of key cardiac components post-MI. 28245984 3 79 dep peri- 419:423 arg1 zones 437:441 zones 437:441 zones 437:441 However, the information about chemical composition, physical structure and molecular mobility of peri- and infarct zones post-MI is rather limited. 28245984 5 80 theme major 748:752 arg1 bands 766:770 major absorptions bands 748:770 major absorptions bands 748:770 The FTIR spectra of healthy and remote myocardial tissue shows amides A, I, II and III associated with proteins in freeze-died tissue as major absorptions bands. 28245984 5 81 theme remote 643:648 arg1 tissue 661:666 healthy and remote myocardial tissue 631:666 healthy and remote myocardial tissue 631:666 The FTIR spectra of healthy and remote myocardial tissue shows amides A, I, II and III associated with proteins in freeze-died tissue as major absorptions bands. 28245984 12 82 theme secondary 1645:1653 arg1 structures 1655:1664 protein secondary structures 1637:1664 protein secondary structures in association with collagen deposition 1637:1704 In conclusion, our results indicate a profound evolution of protein secondary structures in association with collagen deposition and reorganization of water involved in the scar maturation of peri- and infarct zones post-MI. 28245984 3 83 theme physical 374:381 arg1 structure 383:391 physical structure 374:391 physical structure 374:391 However, the information about chemical composition, physical structure and molecular mobility of peri- and infarct zones post-MI is rather limited. 28245984 9 84 from polysaccharides 1303:1317 arg1 residues 1261:1268 residues 1261:1268 residues of carbohydrates in proteins and polysaccharides in ischemic areas 1261:1335 The new spectra bands also indicate an increase in proteoglycans, residues of carbohydrates in proteins and polysaccharides in ischemic areas. 28245984 9 84 from polysaccharides 1303:1317 arg1 proteoglycans 1246:1258 proteoglycans 1246:1258 proteoglycans 1246:1258 The new spectra bands also indicate an increase in proteoglycans, residues of carbohydrates in proteins and polysaccharides in ischemic areas. 28245984 9 84 from polysaccharides 1303:1317 arg1 areas 1331:1335 ischemic areas 1322:1335 ischemic areas 1322:1335 The new spectra bands also indicate an increase in proteoglycans, residues of carbohydrates in proteins and polysaccharides in ischemic areas. 28245984 9 84 from polysaccharides 1303:1317 arg1 carbohydrates 1273:1285 carbohydrates 1273:1285 carbohydrates in proteins and polysaccharides in ischemic areas 1273:1335 The new spectra bands also indicate an increase in proteoglycans, residues of carbohydrates in proteins and polysaccharides in ischemic areas. 28245984 7 85 theme collagen 936:943 arg1 band 965:968 the collagen specific absorption band 932:968 the collagen specific absorption band at 1338cm-1 in the infarct area at 21days post-MI 932:1018 FITR evidenced an increase of the amide A band and the distinct feature of the collagen specific absorption band at 1338cm-1 in the infarct area at 21days post-MI. 28245984 1 86 theme cardiac 109:115 arg1 remodeling 117:126 Adverse cardiac remodeling 101:126 Adverse cardiac remodeling after myocardial infarction (MI) 101:159 Adverse cardiac remodeling after myocardial infarction (MI) causes impaired ventricular function and heart failure. 28245984 3 87 theme peri- 419:423 arg1 composition 361:371 chemical composition 352:371 chemical composition 352:371 However, the information about chemical composition, physical structure and molecular mobility of peri- and infarct zones post-MI is rather limited. 28245984 3 87 theme peri- 419:423 arg1 structure 383:391 physical structure 374:391 physical structure 374:391 However, the information about chemical composition, physical structure and molecular mobility of peri- and infarct zones post-MI is rather limited. 28245984 3 87 theme peri- 419:423 arg1 mobility 407:414 molecular mobility 397:414 molecular mobility 397:414 However, the information about chemical composition, physical structure and molecular mobility of peri- and infarct zones post-MI is rather limited. 28245984 4 88 theme cardiac 583:589 arg1 components 591:600 key cardiac components 579:600 key cardiac components 579:600 The main objective of this work was to explore the spatiotemporal biochemical and biophysical alterations of key cardiac components post-MI. 28245984 11 89 dep proteins 1514:1521 arg1 profile 1531:1537 thermal profile 1523:1537 thermal profile 1523:1537 In infarcted tissue is evidenced the impairment of myofibrillar proteins thermal profile and the emergence of a new structure. 28245984 11 89 dep proteins 1514:1521 arg1 emergence 1547:1555 the emergence 1543:1555 the emergence of a new structure 1543:1574 In infarcted tissue is evidenced the impairment of myofibrillar proteins thermal profile and the emergence of a new structure. 28245984 11 89 dep proteins 1514:1521 arg1 proteins 1514:1521 myofibrillar proteins 1501:1521 myofibrillar proteins thermal profile and the emergence of a new structure 1501:1574 In infarcted tissue is evidenced the impairment of myofibrillar proteins thermal profile and the emergence of a new structure. 28245984 11 90 theme infarcted 1453:1461 arg1 tissue 1463:1468 infarcted tissue 1453:1468 infarcted tissue 1453:1468 In infarcted tissue is evidenced the impairment of myofibrillar proteins thermal profile and the emergence of a new structure. 28245984 8 91 theme important 1059:1067 arg1 shift 1069:1073 an important shift 1056:1073 an important shift of amide I from 1646cm-1 to 1637cm-1 that suggests the predominance of the triple helical conformation in the proteins 1056:1192 At 21days post-MI, it also appears an important shift of amide I from 1646cm-1 to 1637cm-1 that suggests the predominance of the triple helical conformation in the proteins. 28245984 7 92 theme absorption 954:963 arg1 band 965:968 the collagen specific absorption band 932:968 the collagen specific absorption band at 1338cm-1 in the infarct area at 21days post-MI 932:1018 FITR evidenced an increase of the amide A band and the distinct feature of the collagen specific absorption band at 1338cm-1 in the infarct area at 21days post-MI. 28245984 12 93 theme profound 1615:1622 arg1 evolution 1624:1632 a profound evolution 1613:1632 a profound evolution of protein secondary structures in association with collagen deposition and reorganization of water involved in the scar maturation of peri- and infarct zones post-MI 1613:1799 In conclusion, our results indicate a profound evolution of protein secondary structures in association with collagen deposition and reorganization of water involved in the scar maturation of peri- and infarct zones post-MI. 28245984 0 94 theme left 47:50 arg1 infarction 89:98 left ventricle remodeling post-myocardial infarction 47:98 left ventricle remodeling post-myocardial infarction 47:98 Conformational and thermal characterization of left ventricle remodeling post-myocardial infarction. 28245984 12 95 with association 1669:1679 arg1 deposition 1695:1704 collagen deposition 1686:1704 collagen deposition 1686:1704 In conclusion, our results indicate a profound evolution of protein secondary structures in association with collagen deposition and reorganization of water involved in the scar maturation of peri- and infarct zones post-MI. 28245984 5 96 dep amides 674:679 arg1 A 681:681 A 681:681 A 681:681 The FTIR spectra of healthy and remote myocardial tissue shows amides A, I, II and III associated with proteins in freeze-died tissue as major absorptions bands. 28245984 4 97 theme biophysical 552:562 arg1 alterations 564:574 the spatiotemporal biochemical and biophysical alterations 517:574 the spatiotemporal biochemical and biophysical alterations of key cardiac components 517:600 The main objective of this work was to explore the spatiotemporal biochemical and biophysical alterations of key cardiac components post-MI. 28245984 6 98 theme infarcted 776:784 arg1 myocardium 786:795 infarcted myocardium 776:795 infarcted myocardium 776:795 In infarcted myocardium, the spectrum of these main absorptions was deeply altered. 28245984 0 99 theme remodeling 62:71 arg1 infarction 89:98 left ventricle remodeling post-myocardial infarction 47:98 left ventricle remodeling post-myocardial infarction 47:98 Conformational and thermal characterization of left ventricle remodeling post-myocardial infarction. 28245984 3 100 theme infarct 429:435 arg1 composition 361:371 chemical composition 352:371 chemical composition 352:371 However, the information about chemical composition, physical structure and molecular mobility of peri- and infarct zones post-MI is rather limited. 28245984 3 100 theme infarct 429:435 arg1 structure 383:391 physical structure 374:391 physical structure 374:391 However, the information about chemical composition, physical structure and molecular mobility of peri- and infarct zones post-MI is rather limited. 28245984 3 100 theme infarct 429:435 arg1 mobility 407:414 molecular mobility 397:414 molecular mobility 397:414 However, the information about chemical composition, physical structure and molecular mobility of peri- and infarct zones post-MI is rather limited. 28245984 7 101 theme band 899:902 arg1 feature 921:927 the distinct feature 908:927 the distinct feature of the collagen specific absorption band at 1338cm-1 in the infarct area at 21days post-MI 908:1018 FITR evidenced an increase of the amide A band and the distinct feature of the collagen specific absorption band at 1338cm-1 in the infarct area at 21days post-MI. 28245984 7 101 theme band 899:902 arg1 increase 875:882 an increase 872:882 an increase of the amide A band 872:902 FITR evidenced an increase of the amide A band and the distinct feature of the collagen specific absorption band at 1338cm-1 in the infarct area at 21days post-MI. 28245984 9 102 from increase 1234:1241 arg1 residues 1261:1268 residues 1261:1268 residues of carbohydrates in proteins and polysaccharides in ischemic areas 1261:1335 The new spectra bands also indicate an increase in proteoglycans, residues of carbohydrates in proteins and polysaccharides in ischemic areas. 28245984 9 102 from increase 1234:1241 arg1 proteoglycans 1246:1258 proteoglycans 1246:1258 proteoglycans 1246:1258 The new spectra bands also indicate an increase in proteoglycans, residues of carbohydrates in proteins and polysaccharides in ischemic areas. 28245984 9 102 from increase 1234:1241 arg1 carbohydrates 1273:1285 carbohydrates 1273:1285 carbohydrates in proteins and polysaccharides in ischemic areas 1273:1335 The new spectra bands also indicate an increase in proteoglycans, residues of carbohydrates in proteins and polysaccharides in ischemic areas. 28245984 12 103 theme zones 1787:1791 arg1 post-MI 1793:1799 infarct zones post-MI 1779:1799 infarct zones post-MI 1779:1799 In conclusion, our results indicate a profound evolution of protein secondary structures in association with collagen deposition and reorganization of water involved in the scar maturation of peri- and infarct zones post-MI. 28245984 7 104 from increase 875:882 arg1 1338cm-1 973:980 1338cm-1 973:980 1338cm-1 in the infarct area at 21days post-MI 973:1018 FITR evidenced an increase of the amide A band and the distinct feature of the collagen specific absorption band at 1338cm-1 in the infarct area at 21days post-MI. 28245984 10 105 theme Thermal 1338:1344 arg1 analysis 1346:1353 Thermal analysis 1338:1353 Thermal analysis 1338:1353 Thermal analysis indicates a deep increase of unfreezable water/freezable water in peri- and infarcted tissues. 28245984 7 106 theme amide 891:895 arg1 band 899:902 the amide A band 887:902 the amide A band 887:902 FITR evidenced an increase of the amide A band and the distinct feature of the collagen specific absorption band at 1338cm-1 in the infarct area at 21days post-MI. 28758628 6 0 theme 55.7 mol 746:753 arg1 content 707:713 The G+C content 699:713 The G+C content of the DNA of strain S-27T 699:740 The G+C content of the DNA of strain S-27T was 55.7 mol%. 28758628 6 0 theme 55.7 mol 746:753 arg1 % 754:754 55.7 mol% 746:754 55.7 mol% 746:754 The G+C content of the DNA of strain S-27T was 55.7 mol%. 28758628 8 1 theme S-27T 879:883 arg1 wall 864:867 The cell wall 855:867 The cell wall of strain S-27T 855:883 The cell wall of strain S-27T contained d-glutamic acid, glycine, l-alanine, d-alanine, l-ornithine and β-alanine in a molar ratio of 1.0 : 1.6 : 1.4 : 0.6 : 0.9 : 1.1. 28758628 12 2 theme Dictyobacter 1568:1579 arg1 nov. 1598:1601 Dictyobacter aurantiacus gen. nov. 1568:1601 the name Dictyobacter aurantiacus gen. nov. 1559:1601 On the basis of its chemotaxonomic and phenotypic features and phylogenetic position, we concluded that strain S-27T represents a novel genus and species, for which we propose the name Dictyobacter aurantiacus gen. nov., sp. 28758628 12 3 dep name 1563:1566 arg1 nov. 1598:1601 Dictyobacter aurantiacus gen. nov. 1568:1601 the name Dictyobacter aurantiacus gen. nov. 1559:1601 On the basis of its chemotaxonomic and phenotypic features and phylogenetic position, we concluded that strain S-27T represents a novel genus and species, for which we propose the name Dictyobacter aurantiacus gen. nov., sp. 28758628 4 4 located observed 584:591 arg1 pH 596:597 pH 3.0 or 9.2 596:608 pH 596:597 The pH range for growth was pH 3.5 to 8.6; the optimum pH was 6.0, and no growth was observed at pH 3.0 or 9.2. 28758628 4 4 located observed 584:591 arg1 9.2 606:608 9.2 606:608 9.2 606:608 The pH range for growth was pH 3.5 to 8.6; the optimum pH was 6.0, and no growth was observed at pH 3.0 or 9.2. 28758628 4 4 located observed 584:591 arg2 growth 573:578 no growth 570:578 no growth 570:578 The pH range for growth was pH 3.5 to 8.6; the optimum pH was 6.0, and no growth was observed at pH 3.0 or 9.2. 28758628 8 5 from l-alanine 921:929 arg1 ratio 980:984 a molar ratio 972:984 a molar ratio of 1.0 : 1.6 : 1.4 : 0.6 : 0.9 : 1.1 972:1021 The cell wall of strain S-27T contained d-glutamic acid, glycine, l-alanine, d-alanine, l-ornithine and β-alanine in a molar ratio of 1.0 : 1.6 : 1.4 : 0.6 : 0.9 : 1.1. 28758628 10 6 theme cell-wall 1128:1136 arg1 arabinose 1148:1156 arabinose 1148:1156 arabinose 1148:1156 The major cell-wall sugar was arabinose. 28758628 10 6 theme cell-wall 1128:1136 arg1 sugar 1138:1142 The major cell-wall sugar 1118:1142 The major cell-wall sugar 1118:1142 The major cell-wall sugar was arabinose. 28758628 8 7 from acid 906:909 arg1 ratio 980:984 a molar ratio 972:984 a molar ratio of 1.0 : 1.6 : 1.4 : 0.6 : 0.9 : 1.1 972:1021 The cell wall of strain S-27T contained d-glutamic acid, glycine, l-alanine, d-alanine, l-ornithine and β-alanine in a molar ratio of 1.0 : 1.6 : 1.4 : 0.6 : 0.9 : 1.1. 28758628 6 8 theme S-27T 736:740 arg1 DNA 722:724 the DNA 718:724 the DNA of strain S-27T 718:740 The G+C content of the DNA of strain S-27T was 55.7 mol%. 28758628 10 9 theme major 1122:1126 arg1 arabinose 1148:1156 arabinose 1148:1156 arabinose 1148:1156 The major cell-wall sugar was arabinose. 28758628 10 9 theme major 1122:1126 arg1 sugar 1138:1142 The major cell-wall sugar 1118:1142 The major cell-wall sugar 1118:1142 The major cell-wall sugar was arabinose. 28758628 11 10 theme % 1361:1361 arg1 SOSP1-21T 1345:1353 Ktedonobacter racemifer SOSP1-21T 1321:1353 Ktedonobacter racemifer SOSP1-21T (89.6 % sequence identity) 1321:1380 Detailed phylogenetic analysis based on 16S rRNA gene sequences indicated that strain S-27T belongs to the order Ktedonobacterales and is most closely related to Ktedonobacter racemifer SOSP1-21T (89.6 % sequence identity). 28758628 11 10 theme % 1361:1361 arg1 identity 1372:1379 89.6 % sequence identity 1356:1379 89.6 % sequence identity 1356:1379 Detailed phylogenetic analysis based on 16S rRNA gene sequences indicated that strain S-27T belongs to the order Ktedonobacterales and is most closely related to Ktedonobacter racemifer SOSP1-21T (89.6 % sequence identity). 28758628 4 11 theme pH 503:504 arg1 8.6 537:539 8.6 537:539 8.6 537:539 The pH range for growth was pH 3.5 to 8.6; the optimum pH was 6.0, and no growth was observed at pH 3.0 or 9.2. 28758628 4 11 theme pH 503:504 arg1 range 506:510 The pH range 499:510 The pH range for growth 499:521 The pH range for growth was pH 3.5 to 8.6; the optimum pH was 6.0, and no growth was observed at pH 3.0 or 9.2. 28758628 6 12 theme strain 729:734 arg1 S-27T 736:740 strain S-27T 729:740 strain S-27T 729:740 The G+C content of the DNA of strain S-27T was 55.7 mol%. 28758628 11 13 theme order 1266:1270 arg1 Ktedonobacterales 1272:1288 the order Ktedonobacterales 1262:1288 the order Ktedonobacterales 1262:1288 Detailed phylogenetic analysis based on 16S rRNA gene sequences indicated that strain S-27T belongs to the order Ktedonobacterales and is most closely related to Ktedonobacter racemifer SOSP1-21T (89.6 % sequence identity). 28758628 2 14 theme paddy 270:274 arg1 soil 276:279 paddy soil 270:279 paddy soil in Gunung Salak (Mount Salak), West Java, Indonesia 270:331 A mesophilic, Gram-stain-positive, spore-forming bacterium that formed branched mycelia was isolated from paddy soil in Gunung Salak (Mount Salak), West Java, Indonesia. 28758628 3 15 theme growth 420:425 arg1 temperature 427:437 the optimum growth temperature 408:437 the optimum growth temperature 408:437 This strain, designated S-27T, grew at temperatures between 20 and 37 °C; the optimum growth temperature was 25 to 30 °C, and no growth was observed at 15 or 45 °C. 28758628 3 15 theme growth 420:425 arg1 30 °C 449:453 30 °C 449:453 30 °C 449:453 This strain, designated S-27T, grew at temperatures between 20 and 37 °C; the optimum growth temperature was 25 to 30 °C, and no growth was observed at 15 or 45 °C. 28758628 12 16 theme novel 1513:1517 arg1 genus 1519:1523 a novel genus 1511:1523 a novel genus 1511:1523 On the basis of its chemotaxonomic and phenotypic features and phylogenetic position, we concluded that strain S-27T represents a novel genus and species, for which we propose the name Dictyobacter aurantiacus gen. nov., sp. 28758628 4 17 theme optimum 546:552 arg1 6.0 561:563 6.0 561:563 6.0 561:563 The pH range for growth was pH 3.5 to 8.6; the optimum pH was 6.0, and no growth was observed at pH 3.0 or 9.2. 28758628 4 17 theme optimum 546:552 arg1 pH 554:555 the optimum pH 542:555 the optimum pH 542:555 The pH range for growth was pH 3.5 to 8.6; the optimum pH was 6.0, and no growth was observed at pH 3.0 or 9.2. 28758628 6 18 theme DNA 722:724 arg1 content 707:713 The G+C content 699:713 The G+C content of the DNA of strain S-27T 699:740 The G+C content of the DNA of strain S-27T was 55.7 mol%. 28758628 6 18 theme DNA 722:724 arg1 % 754:754 55.7 mol% 746:754 55.7 mol% 746:754 The G+C content of the DNA of strain S-27T was 55.7 mol%. 28758628 7 19 theme major 761:765 arg1 iso-C17  784:791 iso-C17  784:791 iso-C17  784:791 The major fatty acids were iso-C17 : 0 and C16 : 1 2-OH, and the major menaquinone was MK-9 (H2). 28758628 7 19 theme major 761:765 arg1 acids 773:777 The major fatty acids 757:777 The major fatty acids 757:777 The major fatty acids were iso-C17 : 0 and C16 : 1 2-OH, and the major menaquinone was MK-9 (H2). 28758628 12 20 theme aurantiacus 1581:1591 arg1 nov. 1598:1601 Dictyobacter aurantiacus gen. nov. 1568:1601 the name Dictyobacter aurantiacus gen. nov. 1559:1601 On the basis of its chemotaxonomic and phenotypic features and phylogenetic position, we concluded that strain S-27T represents a novel genus and species, for which we propose the name Dictyobacter aurantiacus gen. nov., sp. 28758628 11 21 theme Detailed 1159:1166 arg1 analysis 1181:1188 Detailed phylogenetic analysis 1159:1188 Detailed phylogenetic analysis based on 16S rRNA gene sequences 1159:1221 Detailed phylogenetic analysis based on 16S rRNA gene sequences indicated that strain S-27T belongs to the order Ktedonobacterales and is most closely related to Ktedonobacter racemifer SOSP1-21T (89.6 % sequence identity). 28758628 1 22 theme genus 140:144 arg1 Thermosporothrix 146:161 the genus Thermosporothrix 136:161 the genus Thermosporothrix 136:161 nov., a member of the family Ktedonobacteraceae, isolated from soil, and emended description of the genus Thermosporothrix. 28758628 0 23 theme aurantiacus 13:23 arg1 nov. 30:33 Dictyobacter aurantiacus gen. nov. 0:33 Dictyobacter aurantiacus gen. nov. 0:33 Dictyobacter aurantiacus gen. nov., sp. 28758628 14 24 theme Dictyobacter 1632:1643 arg1 aurantiacus 1645:1655 Dictyobacter aurantiacus 1632:1655 Dictyobacter aurantiacus 1632:1655 The type strain of Dictyobacter aurantiacus is strain S-27T (=NBRC 109595T=InaCC B312T). 28758628 7 25 theme fatty 767:771 arg1 iso-C17  784:791 iso-C17  784:791 iso-C17  784:791 The major fatty acids were iso-C17 : 0 and C16 : 1 2-OH, and the major menaquinone was MK-9 (H2). 28758628 7 25 theme fatty 767:771 arg1 acids 773:777 The major fatty acids 757:777 The major fatty acids 757:777 The major fatty acids were iso-C17 : 0 and C16 : 1 2-OH, and the major menaquinone was MK-9 (H2). 28758628 2 26 dep Salak 304:308 arg1 Mount 298:302 Mount 298:302 Mount 298:302 A mesophilic, Gram-stain-positive, spore-forming bacterium that formed branched mycelia was isolated from paddy soil in Gunung Salak (Mount Salak), West Java, Indonesia. 28758628 3 27 located observed 474:481 arg1 45 °C 492:496 45 °C 492:496 45 °C 492:496 This strain, designated S-27T, grew at temperatures between 20 and 37 °C; the optimum growth temperature was 25 to 30 °C, and no growth was observed at 15 or 45 °C. 28758628 3 27 located observed 474:481 arg1 15 486:487 15 486:487 15 486:487 This strain, designated S-27T, grew at temperatures between 20 and 37 °C; the optimum growth temperature was 25 to 30 °C, and no growth was observed at 15 or 45 °C. 28758628 3 27 located observed 474:481 arg2 growth 463:468 no growth 460:468 no growth 460:468 This strain, designated S-27T, grew at temperatures between 20 and 37 °C; the optimum growth temperature was 25 to 30 °C, and no growth was observed at 15 or 45 °C. 28758628 1 28 theme Thermosporothrix 146:161 arg1 description 121:131 description 121:131 description of the genus Thermosporothrix 121:161 nov., a member of the family Ktedonobacteraceae, isolated from soil, and emended description of the genus Thermosporothrix. 28758628 0 29 theme Dictyobacter 0:11 arg1 nov. 30:33 Dictyobacter aurantiacus gen. nov. 0:33 Dictyobacter aurantiacus gen. nov. 0:33 Dictyobacter aurantiacus gen. nov., sp. 28758628 8 30 from l-ornithine 943:953 arg1 ratio 980:984 a molar ratio 972:984 a molar ratio of 1.0 : 1.6 : 1.4 : 0.6 : 0.9 : 1.1 972:1021 The cell wall of strain S-27T contained d-glutamic acid, glycine, l-alanine, d-alanine, l-ornithine and β-alanine in a molar ratio of 1.0 : 1.6 : 1.4 : 0.6 : 0.9 : 1.1. 28758628 14 31 theme aurantiacus 1645:1655 arg1 S-27T 1667:1671 strain S-27T 1660:1671 strain S-27T (=NBRC 109595T=InaCC B312T) 1660:1699 The type strain of Dictyobacter aurantiacus is strain S-27T (=NBRC 109595T=InaCC B312T). 28758628 14 31 theme aurantiacus 1645:1655 arg1 strain 1622:1627 The type strain 1613:1627 The type strain of Dictyobacter aurantiacus 1613:1655 The type strain of Dictyobacter aurantiacus is strain S-27T (=NBRC 109595T=InaCC B312T). 28758628 1 32 theme family 62:67 arg1 Ktedonobacteraceae 69:86 the family Ktedonobacteraceae 58:86 the family Ktedonobacteraceae 58:86 nov., a member of the family Ktedonobacteraceae, isolated from soil, and emended description of the genus Thermosporothrix. 28758628 11 33 theme rRNA 1203:1206 arg1 sequences 1213:1221 16S rRNA gene sequences 1199:1221 16S rRNA gene sequences 1199:1221 Detailed phylogenetic analysis based on 16S rRNA gene sequences indicated that strain S-27T belongs to the order Ktedonobacterales and is most closely related to Ktedonobacter racemifer SOSP1-21T (89.6 % sequence identity). 28758628 14 34 theme strain 1660:1665 arg1 S-27T 1667:1671 strain S-27T 1660:1671 strain S-27T (=NBRC 109595T=InaCC B312T) 1660:1699 The type strain of Dictyobacter aurantiacus is strain S-27T (=NBRC 109595T=InaCC B312T). 28758628 14 34 theme strain 1660:1665 arg1 B312T 1694:1698 =NBRC 109595T=InaCC B312T 1674:1698 =NBRC 109595T=InaCC B312T 1674:1698 The type strain of Dictyobacter aurantiacus is strain S-27T (=NBRC 109595T=InaCC B312T). 28758628 14 34 theme strain 1660:1665 arg1 strain 1622:1627 The type strain 1613:1627 The type strain of Dictyobacter aurantiacus 1613:1655 The type strain of Dictyobacter aurantiacus is strain S-27T (=NBRC 109595T=InaCC B312T). 28758628 8 35 dep ratio 980:984 arg1  1.4  1000:1004  1.4  1000:1004  1.4  1000:1004 The cell wall of strain S-27T contained d-glutamic acid, glycine, l-alanine, d-alanine, l-ornithine and β-alanine in a molar ratio of 1.0 : 1.6 : 1.4 : 0.6 : 0.9 : 1.1. 28758628 8 35 dep ratio 980:984 arg1  1.1 1018:1021  1.1 1018:1021  1.1 1018:1021 The cell wall of strain S-27T contained d-glutamic acid, glycine, l-alanine, d-alanine, l-ornithine and β-alanine in a molar ratio of 1.0 : 1.6 : 1.4 : 0.6 : 0.9 : 1.1. 28758628 8 35 dep ratio 980:984 arg1  1.6  994:998  1.6  994:998  1.6  994:998 The cell wall of strain S-27T contained d-glutamic acid, glycine, l-alanine, d-alanine, l-ornithine and β-alanine in a molar ratio of 1.0 : 1.6 : 1.4 : 0.6 : 0.9 : 1.1. 28758628 8 35 dep ratio 980:984 arg1  0.9  1012:1016  0.9  1012:1016  0.9  1012:1016 The cell wall of strain S-27T contained d-glutamic acid, glycine, l-alanine, d-alanine, l-ornithine and β-alanine in a molar ratio of 1.0 : 1.6 : 1.4 : 0.6 : 0.9 : 1.1. 28758628 8 35 dep ratio 980:984 arg1  0.6  1006:1010  0.6  1006:1010  0.6  1006:1010 The cell wall of strain S-27T contained d-glutamic acid, glycine, l-alanine, d-alanine, l-ornithine and β-alanine in a molar ratio of 1.0 : 1.6 : 1.4 : 0.6 : 0.9 : 1.1. 28758628 12 36 theme strain 1487:1492 arg1 S-27T 1494:1498 strain S-27T 1487:1498 strain S-27T 1487:1498 On the basis of its chemotaxonomic and phenotypic features and phylogenetic position, we concluded that strain S-27T represents a novel genus and species, for which we propose the name Dictyobacter aurantiacus gen. nov., sp. 28758628 3 37 dep 30 °C 449:453 arg1 to 446:447 to 446:447 to 446:447 This strain, designated S-27T, grew at temperatures between 20 and 37 °C; the optimum growth temperature was 25 to 30 °C, and no growth was observed at 15 or 45 °C. 28758628 11 38 theme gene 1208:1211 arg1 sequences 1213:1221 16S rRNA gene sequences 1199:1221 16S rRNA gene sequences 1199:1221 Detailed phylogenetic analysis based on 16S rRNA gene sequences indicated that strain S-27T belongs to the order Ktedonobacterales and is most closely related to Ktedonobacter racemifer SOSP1-21T (89.6 % sequence identity). 28758628 14 39 theme type 1617:1620 arg1 S-27T 1667:1671 strain S-27T 1660:1671 strain S-27T (=NBRC 109595T=InaCC B312T) 1660:1699 The type strain of Dictyobacter aurantiacus is strain S-27T (=NBRC 109595T=InaCC B312T). 28758628 14 39 theme type 1617:1620 arg1 strain 1622:1627 The type strain 1613:1627 The type strain of Dictyobacter aurantiacus 1613:1655 The type strain of Dictyobacter aurantiacus is strain S-27T (=NBRC 109595T=InaCC B312T). 28758628 0 40 theme gen. 25:28 arg1 nov. 30:33 Dictyobacter aurantiacus gen. nov. 0:33 Dictyobacter aurantiacus gen. nov. 0:33 Dictyobacter aurantiacus gen. nov., sp. 28758628 11 41 theme Ktedonobacter 1321:1333 arg1 SOSP1-21T 1345:1353 Ktedonobacter racemifer SOSP1-21T 1321:1353 Ktedonobacter racemifer SOSP1-21T (89.6 % sequence identity) 1321:1380 Detailed phylogenetic analysis based on 16S rRNA gene sequences indicated that strain S-27T belongs to the order Ktedonobacterales and is most closely related to Ktedonobacter racemifer SOSP1-21T (89.6 % sequence identity). 28758628 11 41 theme Ktedonobacter 1321:1333 arg1 identity 1372:1379 89.6 % sequence identity 1356:1379 89.6 % sequence identity 1356:1379 Detailed phylogenetic analysis based on 16S rRNA gene sequences indicated that strain S-27T belongs to the order Ktedonobacterales and is most closely related to Ktedonobacter racemifer SOSP1-21T (89.6 % sequence identity). 28758628 8 42 from glycine 912:918 arg1 ratio 980:984 a molar ratio 972:984 a molar ratio of 1.0 : 1.6 : 1.4 : 0.6 : 0.9 : 1.1 972:1021 The cell wall of strain S-27T contained d-glutamic acid, glycine, l-alanine, d-alanine, l-ornithine and β-alanine in a molar ratio of 1.0 : 1.6 : 1.4 : 0.6 : 0.9 : 1.1. 28758628 15 43 theme description 1720:1730 arg1 Emendation 1702:1711 Emendation 1702:1711 Emendation of the description of the genus Thermosporothrix 1702:1760 Emendation of the description of the genus Thermosporothrix is also provided. 28758628 11 44 theme 16S 1199:1201 arg1 sequences 1213:1221 16S rRNA gene sequences 1199:1221 16S rRNA gene sequences 1199:1221 Detailed phylogenetic analysis based on 16S rRNA gene sequences indicated that strain S-27T belongs to the order Ktedonobacterales and is most closely related to Ktedonobacter racemifer SOSP1-21T (89.6 % sequence identity). 28758628 8 45 theme 1.0  989:992 arg1 ratio 980:984 a molar ratio 972:984 a molar ratio of 1.0 : 1.6 : 1.4 : 0.6 : 0.9 : 1.1 972:1021 The cell wall of strain S-27T contained d-glutamic acid, glycine, l-alanine, d-alanine, l-ornithine and β-alanine in a molar ratio of 1.0 : 1.6 : 1.4 : 0.6 : 0.9 : 1.1. 28758628 8 46 theme cell 859:862 arg1 wall 864:867 The cell wall 855:867 The cell wall of strain S-27T 855:883 The cell wall of strain S-27T contained d-glutamic acid, glycine, l-alanine, d-alanine, l-ornithine and β-alanine in a molar ratio of 1.0 : 1.6 : 1.4 : 0.6 : 0.9 : 1.1. 28758628 6 47 theme G+C 703:705 arg1 content 707:713 The G+C content 699:713 The G+C content of the DNA of strain S-27T 699:740 The G+C content of the DNA of strain S-27T was 55.7 mol%. 28758628 6 47 theme G+C 703:705 arg1 % 754:754 55.7 mol% 746:754 55.7 mol% 746:754 The G+C content of the DNA of strain S-27T was 55.7 mol%. 28758628 4 48 dep 8.6 537:539 arg1 pH 554:555 the optimum pH 542:555 the optimum pH 542:555 The pH range for growth was pH 3.5 to 8.6; the optimum pH was 6.0, and no growth was observed at pH 3.0 or 9.2. 28758628 4 48 dep 8.6 537:539 arg1 6.0 561:563 6.0 561:563 6.0 561:563 The pH range for growth was pH 3.5 to 8.6; the optimum pH was 6.0, and no growth was observed at pH 3.0 or 9.2. 28758628 4 48 dep 8.6 537:539 arg1 observed 584:591 observed 584:591 was observed at pH 3.0 or 9.2 580:608 The pH range for growth was pH 3.5 to 8.6; the optimum pH was 6.0, and no growth was observed at pH 3.0 or 9.2. 28758628 4 48 dep 8.6 537:539 arg1 to 534:535 to 534:535 to 534:535 The pH range for growth was pH 3.5 to 8.6; the optimum pH was 6.0, and no growth was observed at pH 3.0 or 9.2. 28758628 8 49 theme strain 872:877 arg1 S-27T 879:883 strain S-27T 872:883 strain S-27T 872:883 The cell wall of strain S-27T contained d-glutamic acid, glycine, l-alanine, d-alanine, l-ornithine and β-alanine in a molar ratio of 1.0 : 1.6 : 1.4 : 0.6 : 0.9 : 1.1. 28758628 8 50 theme d-glutamic 895:904 arg1 acid 906:909 d-glutamic acid 895:909 d-glutamic acid 895:909 The cell wall of strain S-27T contained d-glutamic acid, glycine, l-alanine, d-alanine, l-ornithine and β-alanine in a molar ratio of 1.0 : 1.6 : 1.4 : 0.6 : 0.9 : 1.1. 28758628 0 51 dep sp 36:37 arg1 nov. 30:33 Dictyobacter aurantiacus gen. nov. 0:33 Dictyobacter aurantiacus gen. nov. 0:33 Dictyobacter aurantiacus gen. nov., sp. 28758628 9 52 theme polar 1028:1032 arg1 lipids 1034:1039 The polar lipids 1024:1039 The polar lipids 1024:1039 The polar lipids consisted of phosphatidylglycerol, phosphatidylinositol and two glycolipids. 28758628 14 53 theme 109595T=InaCC 1680:1692 arg1 S-27T 1667:1671 strain S-27T 1660:1671 strain S-27T (=NBRC 109595T=InaCC B312T) 1660:1699 The type strain of Dictyobacter aurantiacus is strain S-27T (=NBRC 109595T=InaCC B312T). 28758628 14 53 theme 109595T=InaCC 1680:1692 arg1 B312T 1694:1698 =NBRC 109595T=InaCC B312T 1674:1698 =NBRC 109595T=InaCC B312T 1674:1698 The type strain of Dictyobacter aurantiacus is strain S-27T (=NBRC 109595T=InaCC B312T). 28758628 8 54 theme molar 974:978 arg1 ratio 980:984 a molar ratio 972:984 a molar ratio of 1.0 : 1.6 : 1.4 : 0.6 : 0.9 : 1.1 972:1021 The cell wall of strain S-27T contained d-glutamic acid, glycine, l-alanine, d-alanine, l-ornithine and β-alanine in a molar ratio of 1.0 : 1.6 : 1.4 : 0.6 : 0.9 : 1.1. 28758628 2 55 attach isolated 256:263 arg1 soil 276:279 paddy soil 270:279 paddy soil in Gunung Salak (Mount Salak), West Java, Indonesia 270:331 A mesophilic, Gram-stain-positive, spore-forming bacterium that formed branched mycelia was isolated from paddy soil in Gunung Salak (Mount Salak), West Java, Indonesia. 28758628 2 55 attach isolated 256:263 arg2 bacterium 213:221 A mesophilic, Gram-stain-positive, spore-forming bacterium 164:221 A mesophilic, Gram-stain-positive, spore-forming bacterium that formed branched mycelia 164:250 A mesophilic, Gram-stain-positive, spore-forming bacterium that formed branched mycelia was isolated from paddy soil in Gunung Salak (Mount Salak), West Java, Indonesia. 28758628 11 56 theme phylogenetic 1168:1179 arg1 analysis 1181:1188 Detailed phylogenetic analysis 1159:1188 Detailed phylogenetic analysis based on 16S rRNA gene sequences 1159:1221 Detailed phylogenetic analysis based on 16S rRNA gene sequences indicated that strain S-27T belongs to the order Ktedonobacterales and is most closely related to Ktedonobacter racemifer SOSP1-21T (89.6 % sequence identity). 28758628 8 57 from d-alanine 932:940 arg1 ratio 980:984 a molar ratio 972:984 a molar ratio of 1.0 : 1.6 : 1.4 : 0.6 : 0.9 : 1.1 972:1021 The cell wall of strain S-27T contained d-glutamic acid, glycine, l-alanine, d-alanine, l-ornithine and β-alanine in a molar ratio of 1.0 : 1.6 : 1.4 : 0.6 : 0.9 : 1.1. 28758628 14 58 theme =NBRC 1674:1678 arg1 S-27T 1667:1671 strain S-27T 1660:1671 strain S-27T (=NBRC 109595T=InaCC B312T) 1660:1699 The type strain of Dictyobacter aurantiacus is strain S-27T (=NBRC 109595T=InaCC B312T). 28758628 14 58 theme =NBRC 1674:1678 arg1 B312T 1694:1698 =NBRC 109595T=InaCC B312T 1674:1698 =NBRC 109595T=InaCC B312T 1674:1698 The type strain of Dictyobacter aurantiacus is strain S-27T (=NBRC 109595T=InaCC B312T). 28758628 7 59 theme  1 805:806 arg1 2-OH 808:811  1 2-OH 805:811  1 2-OH 805:811 The major fatty acids were iso-C17 : 0 and C16 : 1 2-OH, and the major menaquinone was MK-9 (H2). 28758628 8 60 contain contained 885:893 arg2 acid 906:909 d-glutamic acid 895:909 d-glutamic acid 895:909 The cell wall of strain S-27T contained d-glutamic acid, glycine, l-alanine, d-alanine, l-ornithine and β-alanine in a molar ratio of 1.0 : 1.6 : 1.4 : 0.6 : 0.9 : 1.1. 28758628 8 60 contain contained 885:893 arg2 glycine 912:918 glycine 912:918 glycine 912:918 The cell wall of strain S-27T contained d-glutamic acid, glycine, l-alanine, d-alanine, l-ornithine and β-alanine in a molar ratio of 1.0 : 1.6 : 1.4 : 0.6 : 0.9 : 1.1. 28758628 8 60 contain contained 885:893 arg2 l-ornithine 943:953 l-ornithine 943:953 l-ornithine 943:953 The cell wall of strain S-27T contained d-glutamic acid, glycine, l-alanine, d-alanine, l-ornithine and β-alanine in a molar ratio of 1.0 : 1.6 : 1.4 : 0.6 : 0.9 : 1.1. 28758628 8 60 contain contained 885:893 arg2 l-alanine 921:929 l-alanine 921:929 l-alanine 921:929 The cell wall of strain S-27T contained d-glutamic acid, glycine, l-alanine, d-alanine, l-ornithine and β-alanine in a molar ratio of 1.0 : 1.6 : 1.4 : 0.6 : 0.9 : 1.1. 28758628 8 60 contain contained 885:893 arg1 wall 864:867 The cell wall 855:867 The cell wall of strain S-27T 855:883 The cell wall of strain S-27T contained d-glutamic acid, glycine, l-alanine, d-alanine, l-ornithine and β-alanine in a molar ratio of 1.0 : 1.6 : 1.4 : 0.6 : 0.9 : 1.1. 28758628 8 60 contain contained 885:893 arg2 β-alanine 959:967 β-alanine 959:967 β-alanine 959:967 The cell wall of strain S-27T contained d-glutamic acid, glycine, l-alanine, d-alanine, l-ornithine and β-alanine in a molar ratio of 1.0 : 1.6 : 1.4 : 0.6 : 0.9 : 1.1. 28758628 8 60 contain contained 885:893 arg2 d-alanine 932:940 d-alanine 932:940 d-alanine 932:940 The cell wall of strain S-27T contained d-glutamic acid, glycine, l-alanine, d-alanine, l-ornithine and β-alanine in a molar ratio of 1.0 : 1.6 : 1.4 : 0.6 : 0.9 : 1.1. 28758628 12 61 theme position 1459:1466 arg1 basis 1390:1394 the basis 1386:1394 the basis of its chemotaxonomic and phenotypic features and phylogenetic position 1386:1466 On the basis of its chemotaxonomic and phenotypic features and phylogenetic position, we concluded that strain S-27T represents a novel genus and species, for which we propose the name Dictyobacter aurantiacus gen. nov., sp. 28758628 15 62 theme genus 1739:1743 arg1 Thermosporothrix 1745:1760 the genus Thermosporothrix 1735:1760 the genus Thermosporothrix 1735:1760 Emendation of the description of the genus Thermosporothrix is also provided. 28758628 12 63 theme gen. 1593:1596 arg1 nov. 1598:1601 Dictyobacter aurantiacus gen. nov. 1568:1601 the name Dictyobacter aurantiacus gen. nov. 1559:1601 On the basis of its chemotaxonomic and phenotypic features and phylogenetic position, we concluded that strain S-27T represents a novel genus and species, for which we propose the name Dictyobacter aurantiacus gen. nov., sp. 28758628 11 64 theme racemifer 1335:1343 arg1 SOSP1-21T 1345:1353 Ktedonobacter racemifer SOSP1-21T 1321:1353 Ktedonobacter racemifer SOSP1-21T (89.6 % sequence identity) 1321:1380 Detailed phylogenetic analysis based on 16S rRNA gene sequences indicated that strain S-27T belongs to the order Ktedonobacterales and is most closely related to Ktedonobacter racemifer SOSP1-21T (89.6 % sequence identity). 28758628 11 64 theme racemifer 1335:1343 arg1 identity 1372:1379 89.6 % sequence identity 1356:1379 89.6 % sequence identity 1356:1379 Detailed phylogenetic analysis based on 16S rRNA gene sequences indicated that strain S-27T belongs to the order Ktedonobacterales and is most closely related to Ktedonobacter racemifer SOSP1-21T (89.6 % sequence identity). 28758628 3 65 theme optimum 412:418 arg1 temperature 427:437 the optimum growth temperature 408:437 the optimum growth temperature 408:437 This strain, designated S-27T, grew at temperatures between 20 and 37 °C; the optimum growth temperature was 25 to 30 °C, and no growth was observed at 15 or 45 °C. 28758628 3 65 theme optimum 412:418 arg1 30 °C 449:453 30 °C 449:453 30 °C 449:453 This strain, designated S-27T, grew at temperatures between 20 and 37 °C; the optimum growth temperature was 25 to 30 °C, and no growth was observed at 15 or 45 °C. 28758628 1 66 theme Ktedonobacteraceae 69:86 arg1 member 48:53 a member 46:53 a member of the family Ktedonobacteraceae 46:86 nov., a member of the family Ktedonobacteraceae, isolated from soil, and emended description of the genus Thermosporothrix. 28758628 1 66 theme Ktedonobacteraceae 69:86 arg1 nov. 40:43 nov. 40:43 nov. 40:43 nov., a member of the family Ktedonobacteraceae, isolated from soil, and emended description of the genus Thermosporothrix. 28758628 2 67 dep mesophilic 166:175 arg1 spore-forming 199:211 spore-forming 199:211 spore-forming 199:211 A mesophilic, Gram-stain-positive, spore-forming bacterium that formed branched mycelia was isolated from paddy soil in Gunung Salak (Mount Salak), West Java, Indonesia. 28758628 2 67 dep mesophilic 166:175 arg1 Gram-stain-positive 178:196 Gram-stain-positive 178:196 Gram-stain-positive 178:196 A mesophilic, Gram-stain-positive, spore-forming bacterium that formed branched mycelia was isolated from paddy soil in Gunung Salak (Mount Salak), West Java, Indonesia. 28758628 7 68 theme major 822:826 arg1 menaquinone 828:838 the major menaquinone 818:838 the major menaquinone 818:838 The major fatty acids were iso-C17 : 0 and C16 : 1 2-OH, and the major menaquinone was MK-9 (H2). 28758628 7 68 theme major 822:826 arg1 MK-9 844:847 MK-9 844:847 MK-9 844:847 The major fatty acids were iso-C17 : 0 and C16 : 1 2-OH, and the major menaquinone was MK-9 (H2). 28758628 2 69 theme mesophilic 166:175 arg1 bacterium 213:221 A mesophilic, Gram-stain-positive, spore-forming bacterium 164:221 A mesophilic, Gram-stain-positive, spore-forming bacterium that formed branched mycelia 164:250 A mesophilic, Gram-stain-positive, spore-forming bacterium that formed branched mycelia was isolated from paddy soil in Gunung Salak (Mount Salak), West Java, Indonesia. 28758628 11 70 theme sequence 1363:1370 arg1 SOSP1-21T 1345:1353 Ktedonobacter racemifer SOSP1-21T 1321:1353 Ktedonobacter racemifer SOSP1-21T (89.6 % sequence identity) 1321:1380 Detailed phylogenetic analysis based on 16S rRNA gene sequences indicated that strain S-27T belongs to the order Ktedonobacterales and is most closely related to Ktedonobacter racemifer SOSP1-21T (89.6 % sequence identity). 28758628 11 70 theme sequence 1363:1370 arg1 identity 1372:1379 89.6 % sequence identity 1356:1379 89.6 % sequence identity 1356:1379 Detailed phylogenetic analysis based on 16S rRNA gene sequences indicated that strain S-27T belongs to the order Ktedonobacterales and is most closely related to Ktedonobacter racemifer SOSP1-21T (89.6 % sequence identity). 28758628 2 71 dep Salak 291:295 arg1 Salak 304:308 Salak 304:308 Salak 304:308 A mesophilic, Gram-stain-positive, spore-forming bacterium that formed branched mycelia was isolated from paddy soil in Gunung Salak (Mount Salak), West Java, Indonesia. 28758628 2 72 from soil 276:279 arg1 Java 317:320 Java 317:320 Java 317:320 A mesophilic, Gram-stain-positive, spore-forming bacterium that formed branched mycelia was isolated from paddy soil in Gunung Salak (Mount Salak), West Java, Indonesia. 28758628 2 72 from soil 276:279 arg1 Salak 291:295 Salak 291:295 Salak 291:295 A mesophilic, Gram-stain-positive, spore-forming bacterium that formed branched mycelia was isolated from paddy soil in Gunung Salak (Mount Salak), West Java, Indonesia. 28758628 12 73 theme chemotaxonomic 1403:1416 arg1 features 1433:1440 its chemotaxonomic and phenotypic features 1399:1440 its chemotaxonomic and phenotypic features 1399:1440 On the basis of its chemotaxonomic and phenotypic features and phylogenetic position, we concluded that strain S-27T represents a novel genus and species, for which we propose the name Dictyobacter aurantiacus gen. nov., sp. 28758628 15 74 theme Thermosporothrix 1745:1760 arg1 description 1720:1730 the description 1716:1730 the description of the genus Thermosporothrix 1716:1760 Emendation of the description of the genus Thermosporothrix is also provided. 28758628 12 75 theme features 1433:1440 arg1 basis 1390:1394 the basis 1386:1394 the basis of its chemotaxonomic and phenotypic features and phylogenetic position 1386:1466 On the basis of its chemotaxonomic and phenotypic features and phylogenetic position, we concluded that strain S-27T represents a novel genus and species, for which we propose the name Dictyobacter aurantiacus gen. nov., sp. 28758628 2 76 theme branched 235:242 arg1 mycelia 244:250 branched mycelia 235:250 branched mycelia 235:250 A mesophilic, Gram-stain-positive, spore-forming bacterium that formed branched mycelia was isolated from paddy soil in Gunung Salak (Mount Salak), West Java, Indonesia. 28758628 11 77 theme strain 1238:1243 arg1 S-27T 1245:1249 strain S-27T 1238:1249 strain S-27T 1238:1249 Detailed phylogenetic analysis based on 16S rRNA gene sequences indicated that strain S-27T belongs to the order Ktedonobacterales and is most closely related to Ktedonobacter racemifer SOSP1-21T (89.6 % sequence identity). 28758628 5 78 theme Strain 611:616 arg1 S-27T 618:622 Strain S-27T 611:622 Strain S-27T 611:622 Strain S-27T was able to hydrolyse polysaccharides such as starch, cellulose and xylan. 28758628 8 79 from β-alanine 959:967 arg1 ratio 980:984 a molar ratio 972:984 a molar ratio of 1.0 : 1.6 : 1.4 : 0.6 : 0.9 : 1.1 972:1021 The cell wall of strain S-27T contained d-glutamic acid, glycine, l-alanine, d-alanine, l-ornithine and β-alanine in a molar ratio of 1.0 : 1.6 : 1.4 : 0.6 : 0.9 : 1.1. 28758628 12 80 theme phenotypic 1422:1431 arg1 features 1433:1440 its chemotaxonomic and phenotypic features 1399:1440 its chemotaxonomic and phenotypic features 1399:1440 On the basis of its chemotaxonomic and phenotypic features and phylogenetic position, we concluded that strain S-27T represents a novel genus and species, for which we propose the name Dictyobacter aurantiacus gen. nov., sp. 28758628 12 81 theme phylogenetic 1446:1457 arg1 position 1459:1466 phylogenetic position 1446:1466 phylogenetic position 1446:1466 On the basis of its chemotaxonomic and phenotypic features and phylogenetic position, we concluded that strain S-27T represents a novel genus and species, for which we propose the name Dictyobacter aurantiacus gen. nov., sp. 29282218 0 0 theme von 76:78 arg1 factor 91:96 von Willebrand factor 76:96 von Willebrand factor clearance 76:106 A novel role for the macrophage galactose-type lectin receptor in mediating von Willebrand factor clearance. 29282218 8 1 theme human 1237:1241 arg1 VWF 1243:1245 human VWF 1237:1245 human VWF 1237:1245 Furthermore, dose-dependent binding of human VWF to purified recombinant human MGL was confirmed using surface plasmon resonance. 29282218 5 2 from experiments 763:773 arg1 mice 793:796 dual VWF/Asgr1 mice 778:796 dual VWF/Asgr1 mice 778:796 Interestingly, in vivo clearance experiments in dual VWF/Asgr1 mice demonstrated enhanced clearance of α2-3Neu-VWF even in the absence of the AMR. 29282218 2 3 theme specific 308:315 arg1 importance 317:326 the specific importance 304:326 (1) the specific importance of N- 300:332 In this study, we investigated (1) the specific importance of N- vs O-linked sialic acid in protecting against VWF clearance and (2) whether additional receptors contribute to the reduced half-life of hyposialylated VWF. 29282218 7 4 theme VWF 1095:1097 arg1 clearance 1067:1075 the markedly enhanced clearance 1045:1075 the markedly enhanced clearance of hyposialylated VWF in VWF/Asgr1 mice 1045:1115 Importantly, the markedly enhanced clearance of hyposialylated VWF in VWF/Asgr1 mice was significantly attenuated in the presence of an anti-MGL inhibitory antibody. 29282218 7 5 theme VWF/Asgr1 1102:1110 arg1 mice 1112:1115 VWF/Asgr1 mice 1102:1115 VWF/Asgr1 mice 1102:1115 Importantly, the markedly enhanced clearance of hyposialylated VWF in VWF/Asgr1 mice was significantly attenuated in the presence of an anti-MGL inhibitory antibody. 29282218 1 6 theme terminal 150:157 arg1 acid 166:169 terminal sialic acid 150:169 terminal sialic acid 150:169 Previous studies have shown that loss of terminal sialic acid causes enhanced von Willebrand factor (VWF) clearance through the Ashwell-Morrell receptor (AMR). 29282218 1 7 theme Ashwell-Morrell 237:251 arg1 AMR 263:265 AMR 263:265 AMR 263:265 Previous studies have shown that loss of terminal sialic acid causes enhanced von Willebrand factor (VWF) clearance through the Ashwell-Morrell receptor (AMR). 29282218 1 7 theme Ashwell-Morrell 237:251 arg1 receptor 253:260 Ashwell-Morrell receptor 237:260 the Ashwell-Morrell receptor (AMR) 233:266 Previous studies have shown that loss of terminal sialic acid causes enhanced von Willebrand factor (VWF) clearance through the Ashwell-Morrell receptor (AMR). 29282218 0 8 theme factor 91:96 arg1 clearance 98:106 von Willebrand factor clearance 76:106 von Willebrand factor clearance 76:106 A novel role for the macrophage galactose-type lectin receptor in mediating von Willebrand factor clearance. 29282218 7 9 theme hyposialylated 1080:1093 arg1 VWF 1095:1097 hyposialylated VWF 1080:1097 hyposialylated VWF 1080:1097 Importantly, the markedly enhanced clearance of hyposialylated VWF in VWF/Asgr1 mice was significantly attenuated in the presence of an anti-MGL inhibitory antibody. 29282218 3 10 theme α2-3-linked 490:500 arg1 acid 509:512 α2-3-linked sialic acid 490:512 α2-3-linked sialic acid 490:512 α2-3-linked sialic acid accounts for <20% of total sialic acid and is predominantly expressed on VWF O-glycans. 29282218 6 11 gly glycoproteins 953:965 arg1 glycoproteins 953:965 glycoproteins 953:965 glycoproteins expressing terminal N-acetylgalactosamine or galactose residues 953:1029 The macrophage galactose-type lectin (MGL) is a C-type lectin that binds to glycoproteins expressing terminal N-acetylgalactosamine or galactose residues. 29282218 0 12 theme Willebrand 80:89 arg1 factor 91:96 von Willebrand factor 76:96 von Willebrand factor clearance 76:106 A novel role for the macrophage galactose-type lectin receptor in mediating von Willebrand factor clearance. 29282218 3 13 theme sialic 502:507 arg1 acid 509:512 α2-3-linked sialic acid 490:512 α2-3-linked sialic acid 490:512 α2-3-linked sialic acid accounts for <20% of total sialic acid and is predominantly expressed on VWF O-glycans. 29282218 2 14 gly hyposialylated 470:483 arg1 VWF 485:487 hyposialylated VWF 470:487 hyposialylated VWF 470:487 In this study, we investigated (1) the specific importance of N- vs O-linked sialic acid in protecting against VWF clearance and (2) whether additional receptors contribute to the reduced half-life of hyposialylated VWF. 29282218 9 15 theme Ag 1353:1354 arg1 levels 1356:1361 plasma VWF:Ag levels 1342:1361 plasma VWF:Ag levels 1342:1361 Additionally, plasma VWF:Ag levels were significantly elevated in MGL1 mice compared with controls. 29282218 6 16 theme C-type 925:930 arg1 lectin 907:912 The macrophage galactose-type lectin 877:912 The macrophage galactose-type lectin (MGL) 877:918 The macrophage galactose-type lectin (MGL) is a C-type lectin that binds to glycoproteins expressing terminal N-acetylgalactosamine or galactose residues. 29282218 6 16 theme C-type 925:930 arg1 lectin 932:937 a C-type lectin 923:937 a C-type lectin that binds to glycoproteins expressing terminal N-acetylgalactosamine or galactose residues 923:1029 The macrophage galactose-type lectin (MGL) is a C-type lectin that binds to glycoproteins expressing terminal N-acetylgalactosamine or galactose residues. 29282218 3 17 link α2-3-linked 490:500 arg1 acid 509:512 α2-3-linked sialic acid 490:512 α2-3-linked sialic acid 490:512 α2-3-linked sialic acid accounts for <20% of total sialic acid and is predominantly expressed on VWF O-glycans. 29282218 5 18 dep in 745:746 arg1 vivo 748:751 vivo 748:751 vivo 748:751 Interestingly, in vivo clearance experiments in dual VWF/Asgr1 mice demonstrated enhanced clearance of α2-3Neu-VWF even in the absence of the AMR. 29282218 6 19 theme galactose 1012:1020 arg1 residues 1022:1029 terminal N-acetylgalactosamine or galactose residues 978:1029 residues 1022:1029 The macrophage galactose-type lectin (MGL) is a C-type lectin that binds to glycoproteins expressing terminal N-acetylgalactosamine or galactose residues. 29282218 8 20 theme purified 1250:1257 arg1 MGL 1277:1279 purified recombinant human MGL 1250:1279 purified recombinant human MGL 1250:1279 Furthermore, dose-dependent binding of human VWF to purified recombinant human MGL was confirmed using surface plasmon resonance. 29282218 5 21 theme α2-3Neu-VWF 833:843 arg1 clearance 820:828 enhanced clearance 811:828 enhanced clearance of α2-3Neu-VWF 811:843 Interestingly, in vivo clearance experiments in dual VWF/Asgr1 mice demonstrated enhanced clearance of α2-3Neu-VWF even in the absence of the AMR. 29282218 1 22 theme sialic 159:164 arg1 acid 166:169 terminal sialic acid 150:169 terminal sialic acid 150:169 Previous studies have shown that loss of terminal sialic acid causes enhanced von Willebrand factor (VWF) clearance through the Ashwell-Morrell receptor (AMR). 29282218 2 23 theme reduced 449:455 arg1 half-life 457:465 the reduced half-life 445:465 the reduced half-life of hyposialylated VWF 445:487 In this study, we investigated (1) the specific importance of N- vs O-linked sialic acid in protecting against VWF clearance and (2) whether additional receptors contribute to the reduced half-life of hyposialylated VWF. 29282218 2 24 theme additional 410:419 arg1 receptors 421:429 additional receptors 410:429 additional receptors 410:429 In this study, we investigated (1) the specific importance of N- vs O-linked sialic acid in protecting against VWF clearance and (2) whether additional receptors contribute to the reduced half-life of hyposialylated VWF. 29282218 7 25 theme inhibitory 1177:1186 arg1 antibody 1188:1195 an anti-MGL inhibitory antibody 1165:1195 an anti-MGL inhibitory antibody 1165:1195 Importantly, the markedly enhanced clearance of hyposialylated VWF in VWF/Asgr1 mice was significantly attenuated in the presence of an anti-MGL inhibitory antibody. 29282218 2 26 dep importance 317:326 arg1 1 301:301 1 301:301 1 301:301 In this study, we investigated (1) the specific importance of N- vs O-linked sialic acid in protecting against VWF clearance and (2) whether additional receptors contribute to the reduced half-life of hyposialylated VWF. 29282218 8 27 theme recombinant 1259:1269 arg1 MGL 1277:1279 purified recombinant human MGL 1250:1279 purified recombinant human MGL 1250:1279 Furthermore, dose-dependent binding of human VWF to purified recombinant human MGL was confirmed using surface plasmon resonance. 29282218 1 28 theme acid 166:169 arg1 loss 142:145 loss 142:145 loss of terminal sialic acid 142:169 Previous studies have shown that loss of terminal sialic acid causes enhanced von Willebrand factor (VWF) clearance through the Ashwell-Morrell receptor (AMR). 29282218 0 29 theme novel 2:6 arg1 role 8:11 A novel role 0:11 A novel role for the macrophage galactose-type lectin receptor in mediating von Willebrand factor clearance. 0:107 A novel role for the macrophage galactose-type lectin receptor in mediating von Willebrand factor clearance. 29282218 4 30 with digestion 625:633 arg1 α2-3Neu-VWF 660:670 α2-3Neu-VWF 660:670 α2-3Neu-VWF 660:670 Nevertheless, specific digestion with α2-3 neuraminidase (α2-3Neu-VWF) was sufficient to cause markedly enhanced VWF clearance. 29282218 4 30 with digestion 625:633 arg1 neuraminidase 645:657 α2-3 neuraminidase 640:657 α2-3 neuraminidase (α2-3Neu-VWF) 640:671 Nevertheless, specific digestion with α2-3 neuraminidase (α2-3Neu-VWF) was sufficient to cause markedly enhanced VWF clearance. 29282218 10 31 theme wild-type 1565:1573 arg1 clearance 1547:1555 the clearance 1543:1555 the clearance of both wild-type and hyposialylated VWF 1543:1596 Collectively, these findings identify MGL as a novel macrophage receptor for VWF that significantly contributes to the clearance of both wild-type and hyposialylated VWF. 29282218 4 32 theme specific 616:623 arg1 digestion 625:633 specific digestion 616:633 specific digestion with α2-3 neuraminidase (α2-3Neu-VWF) 616:671 Nevertheless, specific digestion with α2-3 neuraminidase (α2-3Neu-VWF) was sufficient to cause markedly enhanced VWF clearance. 29282218 7 33 theme enhanced 1058:1065 arg1 clearance 1067:1075 the markedly enhanced clearance 1045:1075 the markedly enhanced clearance of hyposialylated VWF in VWF/Asgr1 mice 1045:1115 Importantly, the markedly enhanced clearance of hyposialylated VWF in VWF/Asgr1 mice was significantly attenuated in the presence of an anti-MGL inhibitory antibody. 29282218 10 34 gly hyposialylated 1579:1592 arg1 VWF 1594:1596 hyposialylated VWF 1579:1596 hyposialylated VWF 1579:1596 Collectively, these findings identify MGL as a novel macrophage receptor for VWF that significantly contributes to the clearance of both wild-type and hyposialylated VWF. 29282218 2 35 dep investigated 287:298 arg1 contribute 431:440 contribute 431:440 contribute to the reduced half-life of hyposialylated VWF 431:487 In this study, we investigated (1) the specific importance of N- vs O-linked sialic acid in protecting against VWF clearance and (2) whether additional receptors contribute to the reduced half-life of hyposialylated VWF. 29282218 1 36 theme enhanced 178:185 arg1 clearance 215:223 enhanced von Willebrand factor (VWF) clearance 178:223 enhanced von Willebrand factor (VWF) clearance 178:223 Previous studies have shown that loss of terminal sialic acid causes enhanced von Willebrand factor (VWF) clearance through the Ashwell-Morrell receptor (AMR). 29282218 10 37 theme VWF 1594:1596 arg1 clearance 1547:1555 the clearance 1543:1555 the clearance of both wild-type and hyposialylated VWF 1543:1596 Collectively, these findings identify MGL as a novel macrophage receptor for VWF that significantly contributes to the clearance of both wild-type and hyposialylated VWF. 29282218 1 38 theme von 187:189 arg1 VWF 210:212 VWF 210:212 VWF 210:212 Previous studies have shown that loss of terminal sialic acid causes enhanced von Willebrand factor (VWF) clearance through the Ashwell-Morrell receptor (AMR). 29282218 1 38 theme von 187:189 arg1 factor 202:207 von Willebrand factor 187:207 enhanced von Willebrand factor (VWF) clearance 178:223 Previous studies have shown that loss of terminal sialic acid causes enhanced von Willebrand factor (VWF) clearance through the Ashwell-Morrell receptor (AMR). 29282218 2 39 theme VWF 380:382 arg1 clearance 384:392 VWF clearance 380:392 VWF clearance 380:392 In this study, we investigated (1) the specific importance of N- vs O-linked sialic acid in protecting against VWF clearance and (2) whether additional receptors contribute to the reduced half-life of hyposialylated VWF. 29282218 7 40 from clearance 1067:1075 arg1 mice 1112:1115 VWF/Asgr1 mice 1102:1115 VWF/Asgr1 mice 1102:1115 Importantly, the markedly enhanced clearance of hyposialylated VWF in VWF/Asgr1 mice was significantly attenuated in the presence of an anti-MGL inhibitory antibody. 29282218 10 41 theme macrophage 1481:1490 arg1 receptor 1492:1499 a novel macrophage receptor 1473:1499 a novel macrophage receptor for VWF that significantly contributes to the clearance of both wild-type and hyposialylated VWF 1473:1596 Collectively, these findings identify MGL as a novel macrophage receptor for VWF that significantly contributes to the clearance of both wild-type and hyposialylated VWF. 29282218 10 41 theme macrophage 1481:1490 arg1 MGL 1466:1468 MGL 1466:1468 MGL 1466:1468 Collectively, these findings identify MGL as a novel macrophage receptor for VWF that significantly contributes to the clearance of both wild-type and hyposialylated VWF. 29282218 3 42 theme VWF 587:589 arg1 O-glycans 591:599 VWF O-glycans 587:599 VWF O-glycans 587:599 α2-3-linked sialic acid accounts for <20% of total sialic acid and is predominantly expressed on VWF O-glycans. 29282218 4 43 theme α2-3 640:643 arg1 α2-3Neu-VWF 660:670 α2-3Neu-VWF 660:670 α2-3Neu-VWF 660:670 Nevertheless, specific digestion with α2-3 neuraminidase (α2-3Neu-VWF) was sufficient to cause markedly enhanced VWF clearance. 29282218 4 43 theme α2-3 640:643 arg1 neuraminidase 645:657 α2-3 neuraminidase 640:657 α2-3 neuraminidase (α2-3Neu-VWF) 640:671 Nevertheless, specific digestion with α2-3 neuraminidase (α2-3Neu-VWF) was sufficient to cause markedly enhanced VWF clearance. 29282218 1 44 theme Willebrand 191:200 arg1 VWF 210:212 VWF 210:212 VWF 210:212 Previous studies have shown that loss of terminal sialic acid causes enhanced von Willebrand factor (VWF) clearance through the Ashwell-Morrell receptor (AMR). 29282218 1 44 theme Willebrand 191:200 arg1 factor 202:207 von Willebrand factor 187:207 enhanced von Willebrand factor (VWF) clearance 178:223 Previous studies have shown that loss of terminal sialic acid causes enhanced von Willebrand factor (VWF) clearance through the Ashwell-Morrell receptor (AMR). 29282218 0 45 theme macrophage 21:30 arg1 receptor 54:61 the macrophage galactose-type lectin receptor 17:61 the macrophage galactose-type lectin receptor 17:61 A novel role for the macrophage galactose-type lectin receptor in mediating von Willebrand factor clearance. 29282218 9 46 theme VWF 1349:1351 arg1 levels 1356:1361 plasma VWF:Ag levels 1342:1361 plasma VWF:Ag levels 1342:1361 Additionally, plasma VWF:Ag levels were significantly elevated in MGL1 mice compared with controls. 29282218 10 47 theme novel 1475:1479 arg1 receptor 1492:1499 a novel macrophage receptor 1473:1499 a novel macrophage receptor for VWF that significantly contributes to the clearance of both wild-type and hyposialylated VWF 1473:1596 Collectively, these findings identify MGL as a novel macrophage receptor for VWF that significantly contributes to the clearance of both wild-type and hyposialylated VWF. 29282218 10 47 theme novel 1475:1479 arg1 MGL 1466:1468 MGL 1466:1468 MGL 1466:1468 Collectively, these findings identify MGL as a novel macrophage receptor for VWF that significantly contributes to the clearance of both wild-type and hyposialylated VWF. 29282218 8 48 theme human 1271:1275 arg1 MGL 1277:1279 purified recombinant human MGL 1250:1279 purified recombinant human MGL 1250:1279 Furthermore, dose-dependent binding of human VWF to purified recombinant human MGL was confirmed using surface plasmon resonance. 29282218 3 49 theme total 535:539 arg1 acid 548:551 total sialic acid 535:551 total sialic acid 535:551 α2-3-linked sialic acid accounts for <20% of total sialic acid and is predominantly expressed on VWF O-glycans. 29282218 2 50 theme N- 331:332 arg1 importance 317:326 the specific importance 304:326 (1) the specific importance of N- 300:332 In this study, we investigated (1) the specific importance of N- vs O-linked sialic acid in protecting against VWF clearance and (2) whether additional receptors contribute to the reduced half-life of hyposialylated VWF. 29282218 1 51 theme factor 202:207 arg1 clearance 215:223 enhanced von Willebrand factor (VWF) clearance 178:223 enhanced von Willebrand factor (VWF) clearance 178:223 Previous studies have shown that loss of terminal sialic acid causes enhanced von Willebrand factor (VWF) clearance through the Ashwell-Morrell receptor (AMR). 29282218 2 52 theme sialic 346:351 arg1 acid 353:356 O-linked sialic acid 337:356 O-linked sialic acid in protecting against VWF clearance 337:392 In this study, we investigated (1) the specific importance of N- vs O-linked sialic acid in protecting against VWF clearance and (2) whether additional receptors contribute to the reduced half-life of hyposialylated VWF. 29282218 2 53 theme VWF 485:487 arg1 half-life 457:465 the reduced half-life 445:465 the reduced half-life of hyposialylated VWF 445:487 In this study, we investigated (1) the specific importance of N- vs O-linked sialic acid in protecting against VWF clearance and (2) whether additional receptors contribute to the reduced half-life of hyposialylated VWF. 29282218 4 54 theme enhanced 706:713 arg1 clearance 719:727 markedly enhanced VWF clearance 697:727 markedly enhanced VWF clearance 697:727 Nevertheless, specific digestion with α2-3 neuraminidase (α2-3Neu-VWF) was sufficient to cause markedly enhanced VWF clearance. 29282218 3 55 theme sialic 541:546 arg1 acid 548:551 total sialic acid 535:551 total sialic acid 535:551 α2-3-linked sialic acid accounts for <20% of total sialic acid and is predominantly expressed on VWF O-glycans. 29282218 5 56 theme enhanced 811:818 arg1 clearance 820:828 enhanced clearance 811:828 enhanced clearance of α2-3Neu-VWF 811:843 Interestingly, in vivo clearance experiments in dual VWF/Asgr1 mice demonstrated enhanced clearance of α2-3Neu-VWF even in the absence of the AMR. 29282218 0 57 theme lectin 47:52 arg1 receptor 54:61 the macrophage galactose-type lectin receptor 17:61 the macrophage galactose-type lectin receptor 17:61 A novel role for the macrophage galactose-type lectin receptor in mediating von Willebrand factor clearance. 29282218 2 58 theme hyposialylated 470:483 arg1 VWF 485:487 hyposialylated VWF 470:487 hyposialylated VWF 470:487 In this study, we investigated (1) the specific importance of N- vs O-linked sialic acid in protecting against VWF clearance and (2) whether additional receptors contribute to the reduced half-life of hyposialylated VWF. 29282218 2 59 dep contribute 431:440 arg1 2 399:399 2 399:399 2 399:399 In this study, we investigated (1) the specific importance of N- vs O-linked sialic acid in protecting against VWF clearance and (2) whether additional receptors contribute to the reduced half-life of hyposialylated VWF. 29282218 2 60 link O-linked 337:344 arg1 acid 353:356 O-linked sialic acid 337:356 O-linked sialic acid in protecting against VWF clearance 337:392 In this study, we investigated (1) the specific importance of N- vs O-linked sialic acid in protecting against VWF clearance and (2) whether additional receptors contribute to the reduced half-life of hyposialylated VWF. 29282218 1 61 theme Previous 109:116 arg1 studies 118:124 Previous studies 109:124 Previous studies 109:124 Previous studies have shown that loss of terminal sialic acid causes enhanced von Willebrand factor (VWF) clearance through the Ashwell-Morrell receptor (AMR). 29282218 0 62 theme galactose-type 32:45 arg1 receptor 54:61 the macrophage galactose-type lectin receptor 17:61 the macrophage galactose-type lectin receptor 17:61 A novel role for the macrophage galactose-type lectin receptor in mediating von Willebrand factor clearance. 29282218 6 63 theme galactose-type 892:905 arg1 lectin 907:912 The macrophage galactose-type lectin 877:912 The macrophage galactose-type lectin (MGL) 877:918 The macrophage galactose-type lectin (MGL) is a C-type lectin that binds to glycoproteins expressing terminal N-acetylgalactosamine or galactose residues. 29282218 6 63 theme galactose-type 892:905 arg1 lectin 932:937 a C-type lectin 923:937 a C-type lectin that binds to glycoproteins expressing terminal N-acetylgalactosamine or galactose residues 923:1029 The macrophage galactose-type lectin (MGL) is a C-type lectin that binds to glycoproteins expressing terminal N-acetylgalactosamine or galactose residues. 29282218 6 63 theme galactose-type 892:905 arg1 MGL 915:917 MGL 915:917 MGL 915:917 The macrophage galactose-type lectin (MGL) is a C-type lectin that binds to glycoproteins expressing terminal N-acetylgalactosamine or galactose residues. 29282218 7 64 theme anti-MGL 1168:1175 arg1 antibody 1188:1195 an anti-MGL inhibitory antibody 1165:1195 an anti-MGL inhibitory antibody 1165:1195 Importantly, the markedly enhanced clearance of hyposialylated VWF in VWF/Asgr1 mice was significantly attenuated in the presence of an anti-MGL inhibitory antibody. 29282218 5 65 theme AMR 872:874 arg1 absence 857:863 the absence 853:863 the absence of the AMR 853:874 Interestingly, in vivo clearance experiments in dual VWF/Asgr1 mice demonstrated enhanced clearance of α2-3Neu-VWF even in the absence of the AMR. 29282218 6 66 theme macrophage 881:890 arg1 lectin 907:912 The macrophage galactose-type lectin 877:912 The macrophage galactose-type lectin (MGL) 877:918 The macrophage galactose-type lectin (MGL) is a C-type lectin that binds to glycoproteins expressing terminal N-acetylgalactosamine or galactose residues. 29282218 6 66 theme macrophage 881:890 arg1 lectin 932:937 a C-type lectin 923:937 a C-type lectin that binds to glycoproteins expressing terminal N-acetylgalactosamine or galactose residues 923:1029 The macrophage galactose-type lectin (MGL) is a C-type lectin that binds to glycoproteins expressing terminal N-acetylgalactosamine or galactose residues. 29282218 6 66 theme macrophage 881:890 arg1 MGL 915:917 MGL 915:917 MGL 915:917 The macrophage galactose-type lectin (MGL) is a C-type lectin that binds to glycoproteins expressing terminal N-acetylgalactosamine or galactose residues. 29282218 9 67 theme plasma 1342:1347 arg1 levels 1356:1361 plasma VWF:Ag levels 1342:1361 plasma VWF:Ag levels 1342:1361 Additionally, plasma VWF:Ag levels were significantly elevated in MGL1 mice compared with controls. 29282218 8 68 theme VWF 1243:1245 arg1 binding 1226:1232 dose-dependent binding 1211:1232 dose-dependent binding of human VWF to purified recombinant human MGL 1211:1279 Furthermore, dose-dependent binding of human VWF to purified recombinant human MGL was confirmed using surface plasmon resonance. 29282218 6 69 theme terminal 978:985 arg1 N-acetylgalactosamine 987:1007 terminal N-acetylgalactosamine or galactose residues 978:1029 N-acetylgalactosamine 987:1007 The macrophage galactose-type lectin (MGL) is a C-type lectin that binds to glycoproteins expressing terminal N-acetylgalactosamine or galactose residues. 29282218 4 70 theme VWF 715:717 arg1 clearance 719:727 markedly enhanced VWF clearance 697:727 markedly enhanced VWF clearance 697:727 Nevertheless, specific digestion with α2-3 neuraminidase (α2-3Neu-VWF) was sufficient to cause markedly enhanced VWF clearance. 29282218 8 71 theme surface 1301:1307 arg1 resonance 1317:1325 surface plasmon resonance 1301:1325 surface plasmon resonance 1301:1325 Furthermore, dose-dependent binding of human VWF to purified recombinant human MGL was confirmed using surface plasmon resonance. 29282218 8 72 theme dose-dependent 1211:1224 arg1 binding 1226:1232 dose-dependent binding 1211:1232 dose-dependent binding of human VWF to purified recombinant human MGL 1211:1279 Furthermore, dose-dependent binding of human VWF to purified recombinant human MGL was confirmed using surface plasmon resonance. 29282218 7 73 gly hyposialylated 1080:1093 arg1 VWF 1095:1097 hyposialylated VWF 1080:1097 hyposialylated VWF 1080:1097 Importantly, the markedly enhanced clearance of hyposialylated VWF in VWF/Asgr1 mice was significantly attenuated in the presence of an anti-MGL inhibitory antibody. 29282218 3 74 theme acid 548:551 arg1 % 530:530 <20% 527:530 <20% of total sialic acid 527:551 α2-3-linked sialic acid accounts for <20% of total sialic acid and is predominantly expressed on VWF O-glycans. 29282218 3 74 theme acid 548:551 arg1 acid 548:551 total sialic acid 535:551 total sialic acid 535:551 α2-3-linked sialic acid accounts for <20% of total sialic acid and is predominantly expressed on VWF O-glycans. 29282218 5 75 theme VWF/Asgr1 783:791 arg1 mice 793:796 dual VWF/Asgr1 mice 778:796 dual VWF/Asgr1 mice 778:796 Interestingly, in vivo clearance experiments in dual VWF/Asgr1 mice demonstrated enhanced clearance of α2-3Neu-VWF even in the absence of the AMR. 29282218 8 76 theme plasmon 1309:1315 arg1 resonance 1317:1325 surface plasmon resonance 1301:1325 surface plasmon resonance 1301:1325 Furthermore, dose-dependent binding of human VWF to purified recombinant human MGL was confirmed using surface plasmon resonance. 29282218 2 77 theme O-linked 337:344 arg1 acid 353:356 O-linked sialic acid 337:356 O-linked sialic acid in protecting against VWF clearance 337:392 In this study, we investigated (1) the specific importance of N- vs O-linked sialic acid in protecting against VWF clearance and (2) whether additional receptors contribute to the reduced half-life of hyposialylated VWF. 29282218 5 78 theme in 745:746 arg1 experiments 763:773 in vivo clearance experiments 745:773 in vivo clearance experiments in dual VWF/Asgr1 mice 745:796 Interestingly, in vivo clearance experiments in dual VWF/Asgr1 mice demonstrated enhanced clearance of α2-3Neu-VWF even in the absence of the AMR. 29282218 5 79 theme dual 778:781 arg1 mice 793:796 dual VWF/Asgr1 mice 778:796 dual VWF/Asgr1 mice 778:796 Interestingly, in vivo clearance experiments in dual VWF/Asgr1 mice demonstrated enhanced clearance of α2-3Neu-VWF even in the absence of the AMR. 29282218 10 80 theme hyposialylated 1579:1592 arg1 VWF 1594:1596 hyposialylated VWF 1579:1596 hyposialylated VWF 1579:1596 Collectively, these findings identify MGL as a novel macrophage receptor for VWF that significantly contributes to the clearance of both wild-type and hyposialylated VWF. 29282218 5 81 theme clearance 753:761 arg1 experiments 763:773 in vivo clearance experiments 745:773 in vivo clearance experiments in dual VWF/Asgr1 mice 745:796 Interestingly, in vivo clearance experiments in dual VWF/Asgr1 mice demonstrated enhanced clearance of α2-3Neu-VWF even in the absence of the AMR. 29282218 9 82 theme MGL1 1394:1397 arg1 mice 1399:1402 MGL1 mice 1394:1402 MGL1 mice 1394:1402 Additionally, plasma VWF:Ag levels were significantly elevated in MGL1 mice compared with controls. 29282218 7 83 theme antibody 1188:1195 arg1 presence 1153:1160 the presence 1149:1160 the presence of an anti-MGL inhibitory antibody 1149:1195 Importantly, the markedly enhanced clearance of hyposialylated VWF in VWF/Asgr1 mice was significantly attenuated in the presence of an anti-MGL inhibitory antibody. 26793173 2 0 theme peripheral 568:577 arg1 PBMCs 604:608 PBMCs 604:608 PBMCs 604:608 Since the fungal cell wall is the first point of contact with the host cells, here we performed a comparison of this organelle in members of the C. parapsilosis complex, and its relevance during interaction with human peripheral blood mononuclear cells (PBMCs). 26793173 2 0 theme peripheral 568:577 arg1 cells 597:601 human peripheral blood mononuclear cells 562:601 human peripheral blood mononuclear cells (PBMCs) 562:609 Since the fungal cell wall is the first point of contact with the host cells, here we performed a comparison of this organelle in members of the C. parapsilosis complex, and its relevance during interaction with human peripheral blood mononuclear cells (PBMCs). 26793173 11 1 theme cell 2204:2207 arg1 antagonist 2237:2246 antagonist 2237:2246 antagonist 2237:2246 In addition, we propose that purified cell wall mannans can be used as antagonist to block specific receptors on innate immune cells. 26793173 11 1 theme cell 2204:2207 arg1 mannans 2214:2220 purified cell wall mannans 2195:2220 purified cell wall mannans 2195:2220 In addition, we propose that purified cell wall mannans can be used as antagonist to block specific receptors on innate immune cells. 26793173 9 2 theme human 1992:1996 arg1 PBMCs 1998:2002 human PBMCs 1992:2002 human PBMCs 1992:2002 Finally, we demonstrated that purified N- and O-mannans from either C. parapsilosis sensu lato or C. albicans are capable to block the recognition of these pathogens by human PBMCs. 26793173 1 3 theme mortality 265:273 arg1 rates 275:279 mortality rates 265:279 mortality rates 265:279 The systemic infections caused by members of the Candida parapsilosis complex are currently associated to high morbility and mortality rates, and are considered as relevant as those caused by Candida albicans. 26793173 10 4 theme complex 2108:2114 arg1 members 2077:2083 the members 2073:2083 the members of the C. parapsilosis complex 2073:2114 Together; our results suggest that the innate immune recognition of the members of the C. parapsilosis complex is differential of that reported for C. albicans. 26793173 5 5 theme mannans 1147:1153 arg1 removal 1127:1133 removal 1127:1133 removal of O-linked mannans 1127:1153 Yeast cells of members of the C. parapsilosis complex stimulated more cytokine production by human PBMCs than C. albicans cells; and this significantly changed upon removal of O-linked mannans, indicating this wall component plays a significant role in cytokine stimulation by C. parapsilosis sensu lato. 26793173 3 6 theme complex 658:664 arg1 members 666:672 the C. parapsilosis complex members 638:672 the C. parapsilosis complex members 638:672 We found that the wall of the C. parapsilosis complex members is similar in composition, but differs to that from C. albicans, with less mannan content and more β-glucan and porosity levels. 26793173 8 7 theme TNFα 1769:1772 arg1 stimulation 1784:1794 TNFα and IL-1β stimulation 1769:1794 TNFα and IL-1β stimulation by members of the complex 1769:1820 Mannose receptor had a significant role during TNFα and IL-1β stimulation by members of the complex. 26793173 2 8 with contact 399:405 arg1 cells 421:425 the host cells 412:425 the host cells 412:425 Since the fungal cell wall is the first point of contact with the host cells, here we performed a comparison of this organelle in members of the C. parapsilosis complex, and its relevance during interaction with human peripheral blood mononuclear cells (PBMCs). 26793173 2 9 theme mononuclear 585:595 arg1 PBMCs 604:608 PBMCs 604:608 PBMCs 604:608 Since the fungal cell wall is the first point of contact with the host cells, here we performed a comparison of this organelle in members of the C. parapsilosis complex, and its relevance during interaction with human peripheral blood mononuclear cells (PBMCs). 26793173 2 9 theme mononuclear 585:595 arg1 cells 597:601 human peripheral blood mononuclear cells 562:601 human peripheral blood mononuclear cells (PBMCs) 562:609 Since the fungal cell wall is the first point of contact with the host cells, here we performed a comparison of this organelle in members of the C. parapsilosis complex, and its relevance during interaction with human peripheral blood mononuclear cells (PBMCs). 26793173 7 10 theme complex 1668:1674 arg1 members 1653:1659 the three members 1643:1659 the three members of the complex 1643:1674 Moreover, we found a strong dependency on β1,3-glucan recognition for the members of the C. parapsilosis complex, but not for live C. albicans cells; whereas TLR4 was required for TNFα production by the three members of the complex, and stimulation of IL-6 by C. orthopsilosis. 26793173 8 11 theme IL-1β 1778:1782 arg1 stimulation 1784:1794 TNFα and IL-1β stimulation 1769:1794 TNFα and IL-1β stimulation by members of the complex 1769:1820 Mannose receptor had a significant role during TNFα and IL-1β stimulation by members of the complex. 26793173 1 12 theme Candida 189:195 arg1 parapsilosis 197:208 Candida parapsilosis 189:208 the Candida parapsilosis complex 185:216 The systemic infections caused by members of the Candida parapsilosis complex are currently associated to high morbility and mortality rates, and are considered as relevant as those caused by Candida albicans. 26793173 10 13 theme parapsilosis 2095:2106 arg1 complex 2108:2114 the C. parapsilosis complex 2088:2114 the C. parapsilosis complex 2088:2114 Together; our results suggest that the innate immune recognition of the members of the C. parapsilosis complex is differential of that reported for C. albicans. 26793173 3 14 from similar 677:683 arg1 composition 688:698 composition 688:698 composition 688:698 We found that the wall of the C. parapsilosis complex members is similar in composition, but differs to that from C. albicans, with less mannan content and more β-glucan and porosity levels. 26793173 0 15 theme Mononuclear 121:131 arg1 Cells 133:137 Human Peripheral Blood Mononuclear Cells 98:137 Human Peripheral Blood Mononuclear Cells 98:137 Members of the Candida parapsilosis Complex and Candida albicans are Differentially Recognized by Human Peripheral Blood Mononuclear Cells. 26793173 5 16 theme C. 992:993 arg1 complex 1008:1014 the C. parapsilosis complex 988:1014 the C. parapsilosis complex 988:1014 Yeast cells of members of the C. parapsilosis complex stimulated more cytokine production by human PBMCs than C. albicans cells; and this significantly changed upon removal of O-linked mannans, indicating this wall component plays a significant role in cytokine stimulation by C. parapsilosis sensu lato. 26793173 1 17 theme complex 210:216 arg1 members 174:180 members 174:180 members of the Candida parapsilosis complex 174:216 The systemic infections caused by members of the Candida parapsilosis complex are currently associated to high morbility and mortality rates, and are considered as relevant as those caused by Candida albicans. 26793173 2 18 theme parapsilosis 498:509 arg1 complex 511:517 the C. parapsilosis complex 491:517 the C. parapsilosis complex 491:517 Since the fungal cell wall is the first point of contact with the host cells, here we performed a comparison of this organelle in members of the C. parapsilosis complex, and its relevance during interaction with human peripheral blood mononuclear cells (PBMCs). 26793173 10 19 theme that 2135:2138 arg1 differential 2119:2130 differential 2119:2130 differential 2119:2130 Together; our results suggest that the innate immune recognition of the members of the C. parapsilosis complex is differential of that reported for C. albicans. 26793173 10 19 theme that 2135:2138 arg1 recognition 2058:2068 the innate immune recognition 2040:2068 the innate immune recognition of the members of the C. parapsilosis complex 2040:2114 Together; our results suggest that the innate immune recognition of the members of the C. parapsilosis complex is differential of that reported for C. albicans. 26793173 4 20 from surface 894:900 arg1 exposure 878:885 increased chitin and β1,3-glucan exposure 845:885 increased chitin and β1,3-glucan exposure at the surface of C. parapsilosis sensu lato 845:930 Furthermore, lectin-based analysis showed increased chitin and β1,3-glucan exposure at the surface of C. parapsilosis sensu lato when compared to C. albicans. 26793173 5 21 theme complex 1008:1014 arg1 members 977:983 members 977:983 members of the C. parapsilosis complex 977:1014 Yeast cells of members of the C. parapsilosis complex stimulated more cytokine production by human PBMCs than C. albicans cells; and this significantly changed upon removal of O-linked mannans, indicating this wall component plays a significant role in cytokine stimulation by C. parapsilosis sensu lato. 26793173 7 22 theme parapsilosis 1536:1547 arg1 complex 1549:1555 the C. parapsilosis complex 1529:1555 the C. parapsilosis complex 1529:1555 Moreover, we found a strong dependency on β1,3-glucan recognition for the members of the C. parapsilosis complex, but not for live C. albicans cells; whereas TLR4 was required for TNFα production by the three members of the complex, and stimulation of IL-6 by C. orthopsilosis. 26793173 8 23 theme complex 1814:1820 arg1 members 1799:1805 members 1799:1805 members of the complex 1799:1820 Mannose receptor had a significant role during TNFα and IL-1β stimulation by members of the complex. 26793173 4 24 theme increased 845:853 arg1 exposure 878:885 increased chitin and β1,3-glucan exposure 845:885 increased chitin and β1,3-glucan exposure at the surface of C. parapsilosis sensu lato 845:930 Furthermore, lectin-based analysis showed increased chitin and β1,3-glucan exposure at the surface of C. parapsilosis sensu lato when compared to C. albicans. 26793173 9 25 theme purified 1853:1860 arg1 N- 1862:1863 N- 1862:1863 N- 1862:1863 Finally, we demonstrated that purified N- and O-mannans from either C. parapsilosis sensu lato or C. albicans are capable to block the recognition of these pathogens by human PBMCs. 26793173 11 26 theme specific 2257:2264 arg1 receptors 2266:2274 specific receptors 2257:2274 specific receptors on innate immune cells 2257:2297 In addition, we propose that purified cell wall mannans can be used as antagonist to block specific receptors on innate immune cells. 26793173 4 27 theme parapsilosis 908:919 arg1 lato 927:930 C. parapsilosis sensu lato 905:930 C. parapsilosis sensu lato 905:930 Furthermore, lectin-based analysis showed increased chitin and β1,3-glucan exposure at the surface of C. parapsilosis sensu lato when compared to C. albicans. 26793173 3 28 theme C. 726:727 arg1 albicans 729:736 C. albicans 726:736 C. albicans 726:736 We found that the wall of the C. parapsilosis complex members is similar in composition, but differs to that from C. albicans, with less mannan content and more β-glucan and porosity levels. 26793173 6 29 theme wall 1314:1317 arg1 surface 1319:1325 the wall surface 1310:1325 the wall surface 1310:1325 When inner wall components were exposed on the wall surface, C. parapsilosis sensu stricto and C. metapsilosis, but not C. orthopsilosis, stimulated higher cytokine production. 26793173 5 30 theme human 1055:1059 arg1 PBMCs 1061:1065 human PBMCs 1055:1065 human PBMCs 1055:1065 Yeast cells of members of the C. parapsilosis complex stimulated more cytokine production by human PBMCs than C. albicans cells; and this significantly changed upon removal of O-linked mannans, indicating this wall component plays a significant role in cytokine stimulation by C. parapsilosis sensu lato. 26793173 4 31 theme lato 927:930 arg1 surface 894:900 the surface 890:900 the surface of C. parapsilosis sensu lato 890:930 Furthermore, lectin-based analysis showed increased chitin and β1,3-glucan exposure at the surface of C. parapsilosis sensu lato when compared to C. albicans. 26793173 10 32 theme innate 2044:2049 arg1 differential 2119:2130 differential 2119:2130 differential 2119:2130 Together; our results suggest that the innate immune recognition of the members of the C. parapsilosis complex is differential of that reported for C. albicans. 26793173 10 32 theme innate 2044:2049 arg1 recognition 2058:2068 the innate immune recognition 2040:2068 the innate immune recognition of the members of the C. parapsilosis complex 2040:2114 Together; our results suggest that the innate immune recognition of the members of the C. parapsilosis complex is differential of that reported for C. albicans. 26793173 7 33 theme β1,3-glucan 1486:1496 arg1 recognition 1498:1508 β1,3-glucan recognition 1486:1508 β1,3-glucan recognition 1486:1508 Moreover, we found a strong dependency on β1,3-glucan recognition for the members of the C. parapsilosis complex, but not for live C. albicans cells; whereas TLR4 was required for TNFα production by the three members of the complex, and stimulation of IL-6 by C. orthopsilosis. 26793173 9 34 theme C. 1891:1892 arg1 lato 1913:1916 C. parapsilosis sensu lato 1891:1916 C. parapsilosis sensu lato 1891:1916 Finally, we demonstrated that purified N- and O-mannans from either C. parapsilosis sensu lato or C. albicans are capable to block the recognition of these pathogens by human PBMCs. 26793173 5 35 theme significant 1195:1205 arg1 role 1207:1210 a significant role 1193:1210 a significant role 1193:1210 Yeast cells of members of the C. parapsilosis complex stimulated more cytokine production by human PBMCs than C. albicans cells; and this significantly changed upon removal of O-linked mannans, indicating this wall component plays a significant role in cytokine stimulation by C. parapsilosis sensu lato. 26793173 5 36 theme more 1027:1030 arg1 production 1041:1050 more cytokine production 1027:1050 more cytokine production 1027:1050 Yeast cells of members of the C. parapsilosis complex stimulated more cytokine production by human PBMCs than C. albicans cells; and this significantly changed upon removal of O-linked mannans, indicating this wall component plays a significant role in cytokine stimulation by C. parapsilosis sensu lato. 26793173 9 37 theme sensu 1907:1911 arg1 lato 1913:1916 C. parapsilosis sensu lato 1891:1916 C. parapsilosis sensu lato 1891:1916 Finally, we demonstrated that purified N- and O-mannans from either C. parapsilosis sensu lato or C. albicans are capable to block the recognition of these pathogens by human PBMCs. 26793173 2 38 theme first 384:388 arg1 wall 372:375 the fungal cell wall 356:375 the fungal cell wall 356:375 Since the fungal cell wall is the first point of contact with the host cells, here we performed a comparison of this organelle in members of the C. parapsilosis complex, and its relevance during interaction with human peripheral blood mononuclear cells (PBMCs). 26793173 2 38 theme first 384:388 arg1 point 390:394 the first point 380:394 the first point of contact with the host cells 380:425 Since the fungal cell wall is the first point of contact with the host cells, here we performed a comparison of this organelle in members of the C. parapsilosis complex, and its relevance during interaction with human peripheral blood mononuclear cells (PBMCs). 26793173 0 39 theme Peripheral 104:113 arg1 Cells 133:137 Human Peripheral Blood Mononuclear Cells 98:137 Human Peripheral Blood Mononuclear Cells 98:137 Members of the Candida parapsilosis Complex and Candida albicans are Differentially Recognized by Human Peripheral Blood Mononuclear Cells. 26793173 6 40 theme sensu 1344:1348 arg1 stricto 1350:1356 sensu stricto 1344:1356 sensu stricto 1344:1356 When inner wall components were exposed on the wall surface, C. parapsilosis sensu stricto and C. metapsilosis, but not C. orthopsilosis, stimulated higher cytokine production. 26793173 8 41 theme Mannose 1722:1728 arg1 receptor 1730:1737 Mannose receptor 1722:1737 Mannose receptor 1722:1737 Mannose receptor had a significant role during TNFα and IL-1β stimulation by members of the complex. 26793173 2 42 theme organelle 467:475 arg1 comparison 448:457 a comparison 446:457 a comparison of this organelle 446:475 Since the fungal cell wall is the first point of contact with the host cells, here we performed a comparison of this organelle in members of the C. parapsilosis complex, and its relevance during interaction with human peripheral blood mononuclear cells (PBMCs). 26793173 7 43 theme C. 1575:1576 arg1 cells 1587:1591 live C. albicans cells 1570:1591 live C. albicans cells 1570:1591 Moreover, we found a strong dependency on β1,3-glucan recognition for the members of the C. parapsilosis complex, but not for live C. albicans cells; whereas TLR4 was required for TNFα production by the three members of the complex, and stimulation of IL-6 by C. orthopsilosis. 26793173 2 44 theme host 416:419 arg1 cells 421:425 the host cells 412:425 the host cells 412:425 Since the fungal cell wall is the first point of contact with the host cells, here we performed a comparison of this organelle in members of the C. parapsilosis complex, and its relevance during interaction with human peripheral blood mononuclear cells (PBMCs). 26793173 5 45 dep C. 1072:1073 arg1 albicans 1075:1082 albicans 1075:1082 albicans 1075:1082 Yeast cells of members of the C. parapsilosis complex stimulated more cytokine production by human PBMCs than C. albicans cells; and this significantly changed upon removal of O-linked mannans, indicating this wall component plays a significant role in cytokine stimulation by C. parapsilosis sensu lato. 26793173 10 46 theme C. 2092:2093 arg1 complex 2108:2114 the C. parapsilosis complex 2088:2114 the C. parapsilosis complex 2088:2114 Together; our results suggest that the innate immune recognition of the members of the C. parapsilosis complex is differential of that reported for C. albicans. 26793173 5 47 theme C. 1239:1240 arg1 lato 1261:1264 C. parapsilosis sensu lato 1239:1264 C. parapsilosis sensu lato 1239:1264 Yeast cells of members of the C. parapsilosis complex stimulated more cytokine production by human PBMCs than C. albicans cells; and this significantly changed upon removal of O-linked mannans, indicating this wall component plays a significant role in cytokine stimulation by C. parapsilosis sensu lato. 26793173 7 48 from dependency 1472:1481 arg1 recognition 1498:1508 β1,3-glucan recognition 1486:1508 β1,3-glucan recognition 1486:1508 Moreover, we found a strong dependency on β1,3-glucan recognition for the members of the C. parapsilosis complex, but not for live C. albicans cells; whereas TLR4 was required for TNFα production by the three members of the complex, and stimulation of IL-6 by C. orthopsilosis. 26793173 5 49 theme sensu 1255:1259 arg1 lato 1261:1264 C. parapsilosis sensu lato 1239:1264 C. parapsilosis sensu lato 1239:1264 Yeast cells of members of the C. parapsilosis complex stimulated more cytokine production by human PBMCs than C. albicans cells; and this significantly changed upon removal of O-linked mannans, indicating this wall component plays a significant role in cytokine stimulation by C. parapsilosis sensu lato. 26793173 11 50 from receptors 2266:2274 arg1 cells 2293:2297 innate immune cells 2279:2297 innate immune cells 2279:2297 In addition, we propose that purified cell wall mannans can be used as antagonist to block specific receptors on innate immune cells. 26793173 0 51 theme parapsilosis 23:34 arg1 Complex 36:42 the Candida parapsilosis Complex and Candida albicans 11:63 Complex 36:42 Members of the Candida parapsilosis Complex and Candida albicans are Differentially Recognized by Human Peripheral Blood Mononuclear Cells. 26793173 6 52 dep parapsilosis 1331:1342 arg1 stricto 1350:1356 sensu stricto 1344:1356 sensu stricto 1344:1356 When inner wall components were exposed on the wall surface, C. parapsilosis sensu stricto and C. metapsilosis, but not C. orthopsilosis, stimulated higher cytokine production. 26793173 0 53 theme albicans 56:63 arg1 Members 0:6 Members 0:6 Members of the Candida parapsilosis Complex and Candida albicans 0:63 Members of the Candida parapsilosis Complex and Candida albicans are Differentially Recognized by Human Peripheral Blood Mononuclear Cells. 26793173 9 54 from albicans 1924:1931 arg1 O-mannans 1869:1877 O-mannans 1869:1877 O-mannans 1869:1877 Finally, we demonstrated that purified N- and O-mannans from either C. parapsilosis sensu lato or C. albicans are capable to block the recognition of these pathogens by human PBMCs. 26793173 9 54 from albicans 1924:1931 arg1 N- 1862:1863 N- 1862:1863 N- 1862:1863 Finally, we demonstrated that purified N- and O-mannans from either C. parapsilosis sensu lato or C. albicans are capable to block the recognition of these pathogens by human PBMCs. 26793173 10 55 theme immune 2051:2056 arg1 differential 2119:2130 differential 2119:2130 differential 2119:2130 Together; our results suggest that the innate immune recognition of the members of the C. parapsilosis complex is differential of that reported for C. albicans. 26793173 10 55 theme immune 2051:2056 arg1 recognition 2058:2068 the innate immune recognition 2040:2068 the innate immune recognition of the members of the C. parapsilosis complex 2040:2114 Together; our results suggest that the innate immune recognition of the members of the C. parapsilosis complex is differential of that reported for C. albicans. 26793173 2 56 theme cell 367:370 arg1 wall 372:375 the fungal cell wall 356:375 the fungal cell wall 356:375 Since the fungal cell wall is the first point of contact with the host cells, here we performed a comparison of this organelle in members of the C. parapsilosis complex, and its relevance during interaction with human peripheral blood mononuclear cells (PBMCs). 26793173 2 56 theme cell 367:370 arg1 point 390:394 the first point 380:394 the first point of contact with the host cells 380:425 Since the fungal cell wall is the first point of contact with the host cells, here we performed a comparison of this organelle in members of the C. parapsilosis complex, and its relevance during interaction with human peripheral blood mononuclear cells (PBMCs). 26793173 1 57 theme high 246:249 arg1 morbility 251:259 high morbility 246:259 high morbility 246:259 The systemic infections caused by members of the Candida parapsilosis complex are currently associated to high morbility and mortality rates, and are considered as relevant as those caused by Candida albicans. 26793173 6 58 theme C. 1328:1329 arg1 parapsilosis 1331:1342 C. parapsilosis sensu stricto and C. metapsilosis, but not C. orthopsilosis, 1328:1403 parapsilosis 1331:1342 When inner wall components were exposed on the wall surface, C. parapsilosis sensu stricto and C. metapsilosis, but not C. orthopsilosis, stimulated higher cytokine production. 26793173 7 59 theme IL-6 1696:1699 arg1 stimulation 1681:1691 stimulation 1681:1691 stimulation of IL-6 by C. orthopsilosis 1681:1719 Moreover, we found a strong dependency on β1,3-glucan recognition for the members of the C. parapsilosis complex, but not for live C. albicans cells; whereas TLR4 was required for TNFα production by the three members of the complex, and stimulation of IL-6 by C. orthopsilosis. 26793173 7 59 theme IL-6 1696:1699 arg1 production 1629:1638 TNFα production 1624:1638 TNFα production by the three members of the complex 1624:1674 Moreover, we found a strong dependency on β1,3-glucan recognition for the members of the C. parapsilosis complex, but not for live C. albicans cells; whereas TLR4 was required for TNFα production by the three members of the complex, and stimulation of IL-6 by C. orthopsilosis. 26793173 11 60 theme purified 2195:2202 arg1 antagonist 2237:2246 antagonist 2237:2246 antagonist 2237:2246 In addition, we propose that purified cell wall mannans can be used as antagonist to block specific receptors on innate immune cells. 26793173 11 60 theme purified 2195:2202 arg1 mannans 2214:2220 purified cell wall mannans 2195:2220 purified cell wall mannans 2195:2220 In addition, we propose that purified cell wall mannans can be used as antagonist to block specific receptors on innate immune cells. 26793173 3 61 theme parapsilosis 645:656 arg1 members 666:672 the C. parapsilosis complex members 638:672 the C. parapsilosis complex members 638:672 We found that the wall of the C. parapsilosis complex members is similar in composition, but differs to that from C. albicans, with less mannan content and more β-glucan and porosity levels. 26793173 8 62 theme significant 1745:1755 arg1 role 1757:1760 a significant role 1743:1760 a significant role 1743:1760 Mannose receptor had a significant role during TNFα and IL-1β stimulation by members of the complex. 26793173 2 63 theme human 562:566 arg1 PBMCs 604:608 PBMCs 604:608 PBMCs 604:608 Since the fungal cell wall is the first point of contact with the host cells, here we performed a comparison of this organelle in members of the C. parapsilosis complex, and its relevance during interaction with human peripheral blood mononuclear cells (PBMCs). 26793173 2 63 theme human 562:566 arg1 cells 597:601 human peripheral blood mononuclear cells 562:601 human peripheral blood mononuclear cells (PBMCs) 562:609 Since the fungal cell wall is the first point of contact with the host cells, here we performed a comparison of this organelle in members of the C. parapsilosis complex, and its relevance during interaction with human peripheral blood mononuclear cells (PBMCs). 26793173 5 64 link O-linked 1138:1145 arg1 mannans 1147:1153 O-linked mannans 1138:1153 O-linked mannans 1138:1153 Yeast cells of members of the C. parapsilosis complex stimulated more cytokine production by human PBMCs than C. albicans cells; and this significantly changed upon removal of O-linked mannans, indicating this wall component plays a significant role in cytokine stimulation by C. parapsilosis sensu lato. 26793173 4 65 theme chitin 855:860 arg1 exposure 878:885 increased chitin and β1,3-glucan exposure 845:885 increased chitin and β1,3-glucan exposure at the surface of C. parapsilosis sensu lato 845:930 Furthermore, lectin-based analysis showed increased chitin and β1,3-glucan exposure at the surface of C. parapsilosis sensu lato when compared to C. albicans. 26793173 11 66 theme immune 2286:2291 arg1 cells 2293:2297 innate immune cells 2279:2297 innate immune cells 2279:2297 In addition, we propose that purified cell wall mannans can be used as antagonist to block specific receptors on innate immune cells. 26793173 5 67 theme O-linked 1138:1145 arg1 mannans 1147:1153 O-linked mannans 1138:1153 O-linked mannans 1138:1153 Yeast cells of members of the C. parapsilosis complex stimulated more cytokine production by human PBMCs than C. albicans cells; and this significantly changed upon removal of O-linked mannans, indicating this wall component plays a significant role in cytokine stimulation by C. parapsilosis sensu lato. 26793173 2 68 with interaction 545:555 arg1 PBMCs 604:608 PBMCs 604:608 PBMCs 604:608 Since the fungal cell wall is the first point of contact with the host cells, here we performed a comparison of this organelle in members of the C. parapsilosis complex, and its relevance during interaction with human peripheral blood mononuclear cells (PBMCs). 26793173 2 68 with interaction 545:555 arg1 cells 597:601 human peripheral blood mononuclear cells 562:601 human peripheral blood mononuclear cells (PBMCs) 562:609 Since the fungal cell wall is the first point of contact with the host cells, here we performed a comparison of this organelle in members of the C. parapsilosis complex, and its relevance during interaction with human peripheral blood mononuclear cells (PBMCs). 26793173 11 69 theme innate 2279:2284 arg1 cells 2293:2297 innate immune cells 2279:2297 innate immune cells 2279:2297 In addition, we propose that purified cell wall mannans can be used as antagonist to block specific receptors on innate immune cells. 26793173 3 70 theme members 666:672 arg1 similar 677:683 similar 677:683 similar 677:683 We found that the wall of the C. parapsilosis complex members is similar in composition, but differs to that from C. albicans, with less mannan content and more β-glucan and porosity levels. 26793173 3 70 theme members 666:672 arg1 wall 630:633 the wall 626:633 the wall of the C. parapsilosis complex members 626:672 We found that the wall of the C. parapsilosis complex members is similar in composition, but differs to that from C. albicans, with less mannan content and more β-glucan and porosity levels. 26793173 2 71 theme blood 579:583 arg1 PBMCs 604:608 PBMCs 604:608 PBMCs 604:608 Since the fungal cell wall is the first point of contact with the host cells, here we performed a comparison of this organelle in members of the C. parapsilosis complex, and its relevance during interaction with human peripheral blood mononuclear cells (PBMCs). 26793173 2 71 theme blood 579:583 arg1 cells 597:601 human peripheral blood mononuclear cells 562:601 human peripheral blood mononuclear cells (PBMCs) 562:609 Since the fungal cell wall is the first point of contact with the host cells, here we performed a comparison of this organelle in members of the C. parapsilosis complex, and its relevance during interaction with human peripheral blood mononuclear cells (PBMCs). 26793173 6 72 theme inner 1272:1276 arg1 components 1283:1292 inner wall components 1272:1292 inner wall components 1272:1292 When inner wall components were exposed on the wall surface, C. parapsilosis sensu stricto and C. metapsilosis, but not C. orthopsilosis, stimulated higher cytokine production. 26793173 1 73 theme parapsilosis 197:208 arg1 complex 210:216 the Candida parapsilosis complex 185:216 the Candida parapsilosis complex 185:216 The systemic infections caused by members of the Candida parapsilosis complex are currently associated to high morbility and mortality rates, and are considered as relevant as those caused by Candida albicans. 26793173 7 74 theme complex 1549:1555 arg1 members 1518:1524 the members 1514:1524 the members of the C. parapsilosis complex 1514:1555 Moreover, we found a strong dependency on β1,3-glucan recognition for the members of the C. parapsilosis complex, but not for live C. albicans cells; whereas TLR4 was required for TNFα production by the three members of the complex, and stimulation of IL-6 by C. orthopsilosis. 26793173 2 75 theme complex 511:517 arg1 members 480:486 members 480:486 members of the C. parapsilosis complex 480:517 Since the fungal cell wall is the first point of contact with the host cells, here we performed a comparison of this organelle in members of the C. parapsilosis complex, and its relevance during interaction with human peripheral blood mononuclear cells (PBMCs). 26793173 2 75 theme complex 511:517 arg1 relevance 528:536 its relevance 524:536 its relevance during interaction with human peripheral blood mononuclear cells (PBMCs) 524:609 Since the fungal cell wall is the first point of contact with the host cells, here we performed a comparison of this organelle in members of the C. parapsilosis complex, and its relevance during interaction with human peripheral blood mononuclear cells (PBMCs). 26793173 5 76 theme parapsilosis 995:1006 arg1 complex 1008:1014 the C. parapsilosis complex 988:1014 the C. parapsilosis complex 988:1014 Yeast cells of members of the C. parapsilosis complex stimulated more cytokine production by human PBMCs than C. albicans cells; and this significantly changed upon removal of O-linked mannans, indicating this wall component plays a significant role in cytokine stimulation by C. parapsilosis sensu lato. 26793173 6 77 theme cytokine 1423:1430 arg1 production 1432:1441 higher cytokine production 1416:1441 higher cytokine production 1416:1441 When inner wall components were exposed on the wall surface, C. parapsilosis sensu stricto and C. metapsilosis, but not C. orthopsilosis, stimulated higher cytokine production. 26793173 7 78 theme C. 1533:1534 arg1 complex 1549:1555 the C. parapsilosis complex 1529:1555 the C. parapsilosis complex 1529:1555 Moreover, we found a strong dependency on β1,3-glucan recognition for the members of the C. parapsilosis complex, but not for live C. albicans cells; whereas TLR4 was required for TNFα production by the three members of the complex, and stimulation of IL-6 by C. orthopsilosis. 26793173 2 79 theme C. 495:496 arg1 complex 511:517 the C. parapsilosis complex 491:517 the C. parapsilosis complex 491:517 Since the fungal cell wall is the first point of contact with the host cells, here we performed a comparison of this organelle in members of the C. parapsilosis complex, and its relevance during interaction with human peripheral blood mononuclear cells (PBMCs). 26793173 4 80 theme lectin-based 816:827 arg1 analysis 829:836 lectin-based analysis 816:836 lectin-based analysis 816:836 Furthermore, lectin-based analysis showed increased chitin and β1,3-glucan exposure at the surface of C. parapsilosis sensu lato when compared to C. albicans. 26793173 5 81 theme members 977:983 arg1 cells 968:972 Yeast cells 962:972 Yeast cells of members of the C. parapsilosis complex 962:1014 Yeast cells of members of the C. parapsilosis complex stimulated more cytokine production by human PBMCs than C. albicans cells; and this significantly changed upon removal of O-linked mannans, indicating this wall component plays a significant role in cytokine stimulation by C. parapsilosis sensu lato. 26793173 3 82 theme porosity 786:793 arg1 levels 795:800 more β-glucan and porosity levels 768:800 more β-glucan and porosity levels 768:800 We found that the wall of the C. parapsilosis complex members is similar in composition, but differs to that from C. albicans, with less mannan content and more β-glucan and porosity levels. 26793173 5 83 theme cytokine 1215:1222 arg1 stimulation 1224:1234 cytokine stimulation 1215:1234 cytokine stimulation by C. parapsilosis sensu lato 1215:1264 Yeast cells of members of the C. parapsilosis complex stimulated more cytokine production by human PBMCs than C. albicans cells; and this significantly changed upon removal of O-linked mannans, indicating this wall component plays a significant role in cytokine stimulation by C. parapsilosis sensu lato. 26793173 3 84 with albicans 729:736 arg1 content 756:762 less mannan content 744:762 less mannan content 744:762 We found that the wall of the C. parapsilosis complex members is similar in composition, but differs to that from C. albicans, with less mannan content and more β-glucan and porosity levels. 26793173 3 84 with albicans 729:736 arg1 levels 795:800 more β-glucan and porosity levels 768:800 more β-glucan and porosity levels 768:800 We found that the wall of the C. parapsilosis complex members is similar in composition, but differs to that from C. albicans, with less mannan content and more β-glucan and porosity levels. 26793173 1 85 theme systemic 144:151 arg1 infections 153:162 The systemic infections 140:162 The systemic infections caused by members of the Candida parapsilosis complex 140:216 The systemic infections caused by members of the Candida parapsilosis complex are currently associated to high morbility and mortality rates, and are considered as relevant as those caused by Candida albicans. 26793173 3 86 theme β-glucan 773:780 arg1 levels 795:800 more β-glucan and porosity levels 768:800 more β-glucan and porosity levels 768:800 We found that the wall of the C. parapsilosis complex members is similar in composition, but differs to that from C. albicans, with less mannan content and more β-glucan and porosity levels. 26793173 4 87 theme C. 905:906 arg1 lato 927:930 C. parapsilosis sensu lato 905:930 C. parapsilosis sensu lato 905:930 Furthermore, lectin-based analysis showed increased chitin and β1,3-glucan exposure at the surface of C. parapsilosis sensu lato when compared to C. albicans. 26793173 7 88 dep C. 1575:1576 arg1 albicans 1578:1585 albicans 1578:1585 albicans 1578:1585 Moreover, we found a strong dependency on β1,3-glucan recognition for the members of the C. parapsilosis complex, but not for live C. albicans cells; whereas TLR4 was required for TNFα production by the three members of the complex, and stimulation of IL-6 by C. orthopsilosis. 26793173 11 89 used used 2229:2232 arg2 antagonist 2237:2246 antagonist 2237:2246 antagonist 2237:2246 In addition, we propose that purified cell wall mannans can be used as antagonist to block specific receptors on innate immune cells. 26793173 11 89 used used 2229:2232 arg2 mannans 2214:2220 purified cell wall mannans 2195:2220 purified cell wall mannans 2195:2220 In addition, we propose that purified cell wall mannans can be used as antagonist to block specific receptors on innate immune cells. 26793173 1 90 theme Candida 332:338 arg1 albicans 340:347 Candida albicans 332:347 Candida albicans 332:347 The systemic infections caused by members of the Candida parapsilosis complex are currently associated to high morbility and mortality rates, and are considered as relevant as those caused by Candida albicans. 26793173 7 91 theme TNFα 1624:1627 arg1 production 1629:1638 TNFα production 1624:1638 TNFα production by the three members of the complex 1624:1674 Moreover, we found a strong dependency on β1,3-glucan recognition for the members of the C. parapsilosis complex, but not for live C. albicans cells; whereas TLR4 was required for TNFα production by the three members of the complex, and stimulation of IL-6 by C. orthopsilosis. 26793173 4 92 theme sensu 921:925 arg1 lato 927:930 C. parapsilosis sensu lato 905:930 C. parapsilosis sensu lato 905:930 Furthermore, lectin-based analysis showed increased chitin and β1,3-glucan exposure at the surface of C. parapsilosis sensu lato when compared to C. albicans. 26793173 0 93 theme Human 98:102 arg1 Cells 133:137 Human Peripheral Blood Mononuclear Cells 98:137 Human Peripheral Blood Mononuclear Cells 98:137 Members of the Candida parapsilosis Complex and Candida albicans are Differentially Recognized by Human Peripheral Blood Mononuclear Cells. 26793173 5 94 theme C. 1072:1073 arg1 cells 1084:1088 C. albicans cells 1072:1088 C. albicans cells 1072:1088 Yeast cells of members of the C. parapsilosis complex stimulated more cytokine production by human PBMCs than C. albicans cells; and this significantly changed upon removal of O-linked mannans, indicating this wall component plays a significant role in cytokine stimulation by C. parapsilosis sensu lato. 26793173 10 95 theme members 2077:2083 arg1 differential 2119:2130 differential 2119:2130 differential 2119:2130 Together; our results suggest that the innate immune recognition of the members of the C. parapsilosis complex is differential of that reported for C. albicans. 26793173 10 95 theme members 2077:2083 arg1 recognition 2058:2068 the innate immune recognition 2040:2068 the innate immune recognition of the members of the C. parapsilosis complex 2040:2114 Together; our results suggest that the innate immune recognition of the members of the C. parapsilosis complex is differential of that reported for C. albicans. 26793173 11 96 theme wall 2209:2212 arg1 antagonist 2237:2246 antagonist 2237:2246 antagonist 2237:2246 In addition, we propose that purified cell wall mannans can be used as antagonist to block specific receptors on innate immune cells. 26793173 11 96 theme wall 2209:2212 arg1 mannans 2214:2220 purified cell wall mannans 2195:2220 purified cell wall mannans 2195:2220 In addition, we propose that purified cell wall mannans can be used as antagonist to block specific receptors on innate immune cells. 26793173 7 97 theme strong 1465:1470 arg1 dependency 1472:1481 a strong dependency 1463:1481 a strong dependency on β1,3-glucan recognition for the members of the C. parapsilosis complex, but not for live C. albicans cells 1463:1591 Moreover, we found a strong dependency on β1,3-glucan recognition for the members of the C. parapsilosis complex, but not for live C. albicans cells; whereas TLR4 was required for TNFα production by the three members of the complex, and stimulation of IL-6 by C. orthopsilosis. 26793173 9 98 theme parapsilosis 1894:1905 arg1 lato 1913:1916 C. parapsilosis sensu lato 1891:1916 C. parapsilosis sensu lato 1891:1916 Finally, we demonstrated that purified N- and O-mannans from either C. parapsilosis sensu lato or C. albicans are capable to block the recognition of these pathogens by human PBMCs. 26793173 3 99 theme mannan 749:754 arg1 content 756:762 less mannan content 744:762 less mannan content 744:762 We found that the wall of the C. parapsilosis complex members is similar in composition, but differs to that from C. albicans, with less mannan content and more β-glucan and porosity levels. 26793173 0 100 theme Blood 115:119 arg1 Cells 133:137 Human Peripheral Blood Mononuclear Cells 98:137 Human Peripheral Blood Mononuclear Cells 98:137 Members of the Candida parapsilosis Complex and Candida albicans are Differentially Recognized by Human Peripheral Blood Mononuclear Cells. 26793173 5 101 theme cytokine 1032:1039 arg1 production 1041:1050 more cytokine production 1027:1050 more cytokine production 1027:1050 Yeast cells of members of the C. parapsilosis complex stimulated more cytokine production by human PBMCs than C. albicans cells; and this significantly changed upon removal of O-linked mannans, indicating this wall component plays a significant role in cytokine stimulation by C. parapsilosis sensu lato. 26793173 3 102 from composition 688:698 arg1 wall 630:633 the wall 626:633 the wall of the C. parapsilosis complex members 626:672 We found that the wall of the C. parapsilosis complex members is similar in composition, but differs to that from C. albicans, with less mannan content and more β-glucan and porosity levels. 26793173 3 102 from composition 688:698 arg1 similar 677:683 similar 677:683 similar 677:683 We found that the wall of the C. parapsilosis complex members is similar in composition, but differs to that from C. albicans, with less mannan content and more β-glucan and porosity levels. 26793173 9 103 theme C. 1921:1922 arg1 albicans 1924:1931 C. albicans 1921:1931 C. albicans 1921:1931 Finally, we demonstrated that purified N- and O-mannans from either C. parapsilosis sensu lato or C. albicans are capable to block the recognition of these pathogens by human PBMCs. 26793173 0 104 theme Candida 15:21 arg1 Complex 36:42 the Candida parapsilosis Complex and Candida albicans 11:63 Complex 36:42 Members of the Candida parapsilosis Complex and Candida albicans are Differentially Recognized by Human Peripheral Blood Mononuclear Cells. 26793173 5 105 theme parapsilosis 1242:1253 arg1 lato 1261:1264 C. parapsilosis sensu lato 1239:1264 C. parapsilosis sensu lato 1239:1264 Yeast cells of members of the C. parapsilosis complex stimulated more cytokine production by human PBMCs than C. albicans cells; and this significantly changed upon removal of O-linked mannans, indicating this wall component plays a significant role in cytokine stimulation by C. parapsilosis sensu lato. 26793173 2 106 theme contact 399:405 arg1 wall 372:375 the fungal cell wall 356:375 the fungal cell wall 356:375 Since the fungal cell wall is the first point of contact with the host cells, here we performed a comparison of this organelle in members of the C. parapsilosis complex, and its relevance during interaction with human peripheral blood mononuclear cells (PBMCs). 26793173 2 106 theme contact 399:405 arg1 point 390:394 the first point 380:394 the first point of contact with the host cells 380:425 Since the fungal cell wall is the first point of contact with the host cells, here we performed a comparison of this organelle in members of the C. parapsilosis complex, and its relevance during interaction with human peripheral blood mononuclear cells (PBMCs). 26793173 0 107 theme Complex 36:42 arg1 Members 0:6 Members 0:6 Members of the Candida parapsilosis Complex and Candida albicans 0:63 Members of the Candida parapsilosis Complex and Candida albicans are Differentially Recognized by Human Peripheral Blood Mononuclear Cells. 26793173 7 108 theme live 1570:1573 arg1 cells 1587:1591 live C. albicans cells 1570:1591 live C. albicans cells 1570:1591 Moreover, we found a strong dependency on β1,3-glucan recognition for the members of the C. parapsilosis complex, but not for live C. albicans cells; whereas TLR4 was required for TNFα production by the three members of the complex, and stimulation of IL-6 by C. orthopsilosis. 26793173 6 109 theme wall 1278:1281 arg1 components 1283:1292 inner wall components 1272:1292 inner wall components 1272:1292 When inner wall components were exposed on the wall surface, C. parapsilosis sensu stricto and C. metapsilosis, but not C. orthopsilosis, stimulated higher cytokine production. 26793173 0 110 theme Candida 48:54 arg1 albicans 56:63 the Candida parapsilosis Complex and Candida albicans 11:63 albicans 56:63 Members of the Candida parapsilosis Complex and Candida albicans are Differentially Recognized by Human Peripheral Blood Mononuclear Cells. 26793173 5 111 theme Yeast 962:966 arg1 cells 968:972 Yeast cells 962:972 Yeast cells of members of the C. parapsilosis complex 962:1014 Yeast cells of members of the C. parapsilosis complex stimulated more cytokine production by human PBMCs than C. albicans cells; and this significantly changed upon removal of O-linked mannans, indicating this wall component plays a significant role in cytokine stimulation by C. parapsilosis sensu lato. 26793173 4 112 theme β1,3-glucan 866:876 arg1 exposure 878:885 increased chitin and β1,3-glucan exposure 845:885 increased chitin and β1,3-glucan exposure at the surface of C. parapsilosis sensu lato 845:930 Furthermore, lectin-based analysis showed increased chitin and β1,3-glucan exposure at the surface of C. parapsilosis sensu lato when compared to C. albicans. 26793173 9 113 theme pathogens 1979:1987 arg1 recognition 1958:1968 the recognition 1954:1968 the recognition of these pathogens by human PBMCs 1954:2002 Finally, we demonstrated that purified N- and O-mannans from either C. parapsilosis sensu lato or C. albicans are capable to block the recognition of these pathogens by human PBMCs. 26793173 6 114 theme higher 1416:1421 arg1 production 1432:1441 higher cytokine production 1416:1441 higher cytokine production 1416:1441 When inner wall components were exposed on the wall surface, C. parapsilosis sensu stricto and C. metapsilosis, but not C. orthopsilosis, stimulated higher cytokine production. 26793173 9 115 from lato 1913:1916 arg1 O-mannans 1869:1877 O-mannans 1869:1877 O-mannans 1869:1877 Finally, we demonstrated that purified N- and O-mannans from either C. parapsilosis sensu lato or C. albicans are capable to block the recognition of these pathogens by human PBMCs. 26793173 9 115 from lato 1913:1916 arg1 N- 1862:1863 N- 1862:1863 N- 1862:1863 Finally, we demonstrated that purified N- and O-mannans from either C. parapsilosis sensu lato or C. albicans are capable to block the recognition of these pathogens by human PBMCs. 26793173 8 116 contain had 1739:1741 arg1 receptor 1730:1737 Mannose receptor 1722:1737 Mannose receptor 1722:1737 Mannose receptor had a significant role during TNFα and IL-1β stimulation by members of the complex. 26793173 8 116 contain had 1739:1741 arg2 role 1757:1760 a significant role 1743:1760 a significant role 1743:1760 Mannose receptor had a significant role during TNFα and IL-1β stimulation by members of the complex. 26793173 3 117 theme C. 642:643 arg1 members 666:672 the C. parapsilosis complex members 638:672 the C. parapsilosis complex members 638:672 We found that the wall of the C. parapsilosis complex members is similar in composition, but differs to that from C. albicans, with less mannan content and more β-glucan and porosity levels. 26793173 2 118 theme fungal 360:365 arg1 wall 372:375 the fungal cell wall 356:375 the fungal cell wall 356:375 Since the fungal cell wall is the first point of contact with the host cells, here we performed a comparison of this organelle in members of the C. parapsilosis complex, and its relevance during interaction with human peripheral blood mononuclear cells (PBMCs). 26793173 2 118 theme fungal 360:365 arg1 point 390:394 the first point 380:394 the first point of contact with the host cells 380:425 Since the fungal cell wall is the first point of contact with the host cells, here we performed a comparison of this organelle in members of the C. parapsilosis complex, and its relevance during interaction with human peripheral blood mononuclear cells (PBMCs). 26793173 5 119 theme wall 1172:1175 arg1 component 1177:1185 this wall component 1167:1185 this wall component 1167:1185 Yeast cells of members of the C. parapsilosis complex stimulated more cytokine production by human PBMCs than C. albicans cells; and this significantly changed upon removal of O-linked mannans, indicating this wall component plays a significant role in cytokine stimulation by C. parapsilosis sensu lato. 26405108 0 0 theme alvei 41:45 arg1 CCM 47:49 Paenibacillus alvei CCM 27:49 Paenibacillus alvei CCM 27:49 Flagellin glycosylation in Paenibacillus alvei CCM 2051T. 26405108 6 1 theme hag 980:982 arg1 gene 984:987 the hag gene 976:987 the hag gene on the bacterial chromosome 976:1015 Downstream of the hag gene on the bacterial chromosome, two open reading frames (PAV_2c01630, PAV_2c01640) encoding putative glycosyltransferases were shown to constitute a flagellin glycosylation island. 26405108 2 2 theme various 219:225 arg1 bacteria 241:248 various Gram-negative bacteria 219:248 various Gram-negative bacteria 219:248 The basis of flagellin glycosylation has been studied for various Gram-negative bacteria, but less is known about flagellin glycans of Gram-positive bacteria including Paenibacillus alvei, a secondary invader of honeybee colonies diseased with European foulbrood. 26405108 5 3 theme glycosylation 947:959 arg1 glycosylation 947:959 glycosylation 947:959 glycosylation 947:959 Analysis on purified flagellin demonstrated that the 30-kDa Hag protein (PAV_2c01710) is modified with an O-linked trisaccharide comprised of one hexose and two N-acetyl-hexosamine residues, at three sites of glycosylation. 26405108 5 3 theme glycosylation 947:959 arg1 sites 938:942 three sites 932:942 three sites of glycosylation 932:959 Analysis on purified flagellin demonstrated that the 30-kDa Hag protein (PAV_2c01710) is modified with an O-linked trisaccharide comprised of one hexose and two N-acetyl-hexosamine residues, at three sites of glycosylation. 26405108 3 4 theme biofilm 576:582 arg1 formation 584:592 abolished biofilm formation 566:592 abolished biofilm formation of a non-motile P. alvei mutant defective in the flagellin protein Hag 566:663 Paenibacillus alvei CCM 2051(T) swarms vigorously on solidified culture medium, with swarming relying on functional flagella as evidenced by abolished biofilm formation of a non-motile P. alvei mutant defective in the flagellin protein Hag. 26405108 4 5 theme flagella 711:718 arg1 glycobiology 676:687 the glycobiology 672:687 the glycobiology of the polar P. alvei flagella 672:718 Here, the glycobiology of the polar P. alvei flagella was investigated. 26405108 3 6 theme non-motile 599:608 arg1 mutant 619:624 a non-motile P. alvei mutant 597:624 a non-motile P. alvei mutant defective in the flagellin protein Hag 597:663 Paenibacillus alvei CCM 2051(T) swarms vigorously on solidified culture medium, with swarming relying on functional flagella as evidenced by abolished biofilm formation of a non-motile P. alvei mutant defective in the flagellin protein Hag. 26405108 8 7 theme flagella 1521:1528 arg1 glycosylation 1530:1542 flagella glycosylation 1521:1542 flagella glycosylation 1521:1542 This study reveals that flagellin glycosylation in P. alvei is pivotal to flagella formation and bacterial motility in vivo, and simultaneously identifies flagella glycosylation as a second protein O-glycosylation system in this bacterium, in addition to the well-investigated S-layer tyrosine O-glycosylation pathway. 26405108 8 7 theme flagella 1521:1528 arg1 system 1580:1585 a second protein O-glycosylation system 1547:1585 a second protein O-glycosylation system in this bacterium 1547:1603 This study reveals that flagellin glycosylation in P. alvei is pivotal to flagella formation and bacterial motility in vivo, and simultaneously identifies flagella glycosylation as a second protein O-glycosylation system in this bacterium, in addition to the well-investigated S-layer tyrosine O-glycosylation pathway. 26405108 6 8 theme open 1022:1025 arg1 frames 1035:1040 two open reading frames 1018:1040 two open reading frames (PAV_2c01630, PAV_2c01640) encoding putative glycosyltransferases 1018:1106 Downstream of the hag gene on the bacterial chromosome, two open reading frames (PAV_2c01630, PAV_2c01640) encoding putative glycosyltransferases were shown to constitute a flagellin glycosylation island. 26405108 7 9 theme gel 1269:1271 arg1 electrophoresis 1273:1287 sodium dodecyl sulfate polyacrylamide gel electrophoresis 1231:1287 sodium dodecyl sulfate polyacrylamide gel electrophoresis as well as loss of extracellular flagella production and bacterial motility 1231:1363 Mutants defective in these genes exhibited altered migration in sodium dodecyl sulfate polyacrylamide gel electrophoresis as well as loss of extracellular flagella production and bacterial motility. 26405108 3 10 theme defective 626:634 arg1 mutant 619:624 a non-motile P. alvei mutant 597:624 a non-motile P. alvei mutant defective in the flagellin protein Hag 597:663 Paenibacillus alvei CCM 2051(T) swarms vigorously on solidified culture medium, with swarming relying on functional flagella as evidenced by abolished biofilm formation of a non-motile P. alvei mutant defective in the flagellin protein Hag. 26405108 1 11 theme flagella 151:158 arg1 functionality 124:136 the functionality 120:136 the functionality of bacterial flagella 120:158 Flagellin glycosylation impacts, in several documented cases, the functionality of bacterial flagella. 26405108 8 12 theme second 1549:1554 arg1 glycosylation 1530:1542 flagella glycosylation 1521:1542 flagella glycosylation 1521:1542 This study reveals that flagellin glycosylation in P. alvei is pivotal to flagella formation and bacterial motility in vivo, and simultaneously identifies flagella glycosylation as a second protein O-glycosylation system in this bacterium, in addition to the well-investigated S-layer tyrosine O-glycosylation pathway. 26405108 8 12 theme second 1549:1554 arg1 system 1580:1585 a second protein O-glycosylation system 1547:1585 a second protein O-glycosylation system in this bacterium 1547:1603 This study reveals that flagellin glycosylation in P. alvei is pivotal to flagella formation and bacterial motility in vivo, and simultaneously identifies flagella glycosylation as a second protein O-glycosylation system in this bacterium, in addition to the well-investigated S-layer tyrosine O-glycosylation pathway. 26405108 4 13 theme P. 702:703 arg1 flagella 711:718 the polar P. alvei flagella 692:718 the polar P. alvei flagella 692:718 Here, the glycobiology of the polar P. alvei flagella was investigated. 26405108 7 14 theme sulfate 1246:1252 arg1 electrophoresis 1273:1287 sodium dodecyl sulfate polyacrylamide gel electrophoresis 1231:1287 sodium dodecyl sulfate polyacrylamide gel electrophoresis as well as loss of extracellular flagella production and bacterial motility 1231:1363 Mutants defective in these genes exhibited altered migration in sodium dodecyl sulfate polyacrylamide gel electrophoresis as well as loss of extracellular flagella production and bacterial motility. 26405108 6 15 theme bacterial 996:1004 arg1 chromosome 1006:1015 the bacterial chromosome 992:1015 the bacterial chromosome 992:1015 Downstream of the hag gene on the bacterial chromosome, two open reading frames (PAV_2c01630, PAV_2c01640) encoding putative glycosyltransferases were shown to constitute a flagellin glycosylation island. 26405108 5 16 gly glycosylation 947:959 arg2 sites 938:942 three sites 932:942 three sites of glycosylation 932:959 Analysis on purified flagellin demonstrated that the 30-kDa Hag protein (PAV_2c01710) is modified with an O-linked trisaccharide comprised of one hexose and two N-acetyl-hexosamine residues, at three sites of glycosylation. 26405108 5 16 gly glycosylation 947:959 arg2 glycosylation 947:959 glycosylation 947:959 glycosylation 947:959 Analysis on purified flagellin demonstrated that the 30-kDa Hag protein (PAV_2c01710) is modified with an O-linked trisaccharide comprised of one hexose and two N-acetyl-hexosamine residues, at three sites of glycosylation. 26405108 8 17 theme O-glycosylation 1564:1578 arg1 glycosylation 1530:1542 flagella glycosylation 1521:1542 flagella glycosylation 1521:1542 This study reveals that flagellin glycosylation in P. alvei is pivotal to flagella formation and bacterial motility in vivo, and simultaneously identifies flagella glycosylation as a second protein O-glycosylation system in this bacterium, in addition to the well-investigated S-layer tyrosine O-glycosylation pathway. 26405108 8 17 theme O-glycosylation 1564:1578 arg1 system 1580:1585 a second protein O-glycosylation system 1547:1585 a second protein O-glycosylation system in this bacterium 1547:1603 This study reveals that flagellin glycosylation in P. alvei is pivotal to flagella formation and bacterial motility in vivo, and simultaneously identifies flagella glycosylation as a second protein O-glycosylation system in this bacterium, in addition to the well-investigated S-layer tyrosine O-glycosylation pathway. 26405108 8 18 theme flagellin 1390:1398 arg1 glycosylation 1400:1412 flagellin glycosylation 1390:1412 flagellin glycosylation in P. alvei 1390:1424 This study reveals that flagellin glycosylation in P. alvei is pivotal to flagella formation and bacterial motility in vivo, and simultaneously identifies flagella glycosylation as a second protein O-glycosylation system in this bacterium, in addition to the well-investigated S-layer tyrosine O-glycosylation pathway. 26405108 7 19 theme sodium 1231:1236 arg1 electrophoresis 1273:1287 sodium dodecyl sulfate polyacrylamide gel electrophoresis 1231:1287 sodium dodecyl sulfate polyacrylamide gel electrophoresis as well as loss of extracellular flagella production and bacterial motility 1231:1363 Mutants defective in these genes exhibited altered migration in sodium dodecyl sulfate polyacrylamide gel electrophoresis as well as loss of extracellular flagella production and bacterial motility. 26405108 3 20 from defective 626:634 arg1 Hag 661:663 the flagellin protein Hag 639:663 the flagellin protein Hag 639:663 Paenibacillus alvei CCM 2051(T) swarms vigorously on solidified culture medium, with swarming relying on functional flagella as evidenced by abolished biofilm formation of a non-motile P. alvei mutant defective in the flagellin protein Hag. 26405108 5 21 theme purified 750:757 arg1 flagellin 759:767 purified flagellin 750:767 purified flagellin 750:767 Analysis on purified flagellin demonstrated that the 30-kDa Hag protein (PAV_2c01710) is modified with an O-linked trisaccharide comprised of one hexose and two N-acetyl-hexosamine residues, at three sites of glycosylation. 26405108 0 22 theme Flagellin 0:8 arg1 glycosylation 10:22 Flagellin glycosylation 0:22 Flagellin glycosylation in Paenibacillus alvei CCM 0:49 Flagellin glycosylation in Paenibacillus alvei CCM 2051T. 26405108 1 23 theme several 94:100 arg1 cases 113:117 several documented cases 94:117 several documented cases 94:117 Flagellin glycosylation impacts, in several documented cases, the functionality of bacterial flagella. 26405108 8 24 gly glycosylation 1400:1412 arg1 alvei 1420:1424 P. alvei 1417:1424 P. alvei 1417:1424 This study reveals that flagellin glycosylation in P. alvei is pivotal to flagella formation and bacterial motility in vivo, and simultaneously identifies flagella glycosylation as a second protein O-glycosylation system in this bacterium, in addition to the well-investigated S-layer tyrosine O-glycosylation pathway. 26405108 7 25 theme motility 1356:1363 arg1 electrophoresis 1273:1287 sodium dodecyl sulfate polyacrylamide gel electrophoresis 1231:1287 sodium dodecyl sulfate polyacrylamide gel electrophoresis as well as loss of extracellular flagella production and bacterial motility 1231:1363 Mutants defective in these genes exhibited altered migration in sodium dodecyl sulfate polyacrylamide gel electrophoresis as well as loss of extracellular flagella production and bacterial motility. 26405108 7 25 theme motility 1356:1363 arg1 loss 1300:1303 loss 1300:1303 sodium dodecyl sulfate polyacrylamide gel electrophoresis as well as loss of extracellular flagella production and bacterial motility 1231:1363 Mutants defective in these genes exhibited altered migration in sodium dodecyl sulfate polyacrylamide gel electrophoresis as well as loss of extracellular flagella production and bacterial motility. 26405108 3 26 theme alvei 439:443 arg1 T 454:454 T 454:454 T 454:454 Paenibacillus alvei CCM 2051(T) swarms vigorously on solidified culture medium, with swarming relying on functional flagella as evidenced by abolished biofilm formation of a non-motile P. alvei mutant defective in the flagellin protein Hag. 26405108 3 26 theme alvei 439:443 arg1 2051 449:452 Paenibacillus alvei CCM 2051 425:452 Paenibacillus alvei CCM 2051(T) 425:455 Paenibacillus alvei CCM 2051(T) swarms vigorously on solidified culture medium, with swarming relying on functional flagella as evidenced by abolished biofilm formation of a non-motile P. alvei mutant defective in the flagellin protein Hag. 26405108 6 27 from gene 984:987 arg1 chromosome 1006:1015 the bacterial chromosome 992:1015 the bacterial chromosome 992:1015 Downstream of the hag gene on the bacterial chromosome, two open reading frames (PAV_2c01630, PAV_2c01640) encoding putative glycosyltransferases were shown to constitute a flagellin glycosylation island. 26405108 2 28 theme flagellin 174:182 arg1 glycosylation 184:196 flagellin glycosylation 174:196 flagellin glycosylation 174:196 The basis of flagellin glycosylation has been studied for various Gram-negative bacteria, but less is known about flagellin glycans of Gram-positive bacteria including Paenibacillus alvei, a secondary invader of honeybee colonies diseased with European foulbrood. 26405108 8 29 theme flagella 1440:1447 arg1 formation 1449:1457 flagella formation 1440:1457 flagella formation 1440:1457 This study reveals that flagellin glycosylation in P. alvei is pivotal to flagella formation and bacterial motility in vivo, and simultaneously identifies flagella glycosylation as a second protein O-glycosylation system in this bacterium, in addition to the well-investigated S-layer tyrosine O-glycosylation pathway. 26405108 5 30 theme Hag 798:800 arg1 protein 802:808 the 30-kDa Hag protein 787:808 the 30-kDa Hag protein (PAV_2c01710) 787:822 Analysis on purified flagellin demonstrated that the 30-kDa Hag protein (PAV_2c01710) is modified with an O-linked trisaccharide comprised of one hexose and two N-acetyl-hexosamine residues, at three sites of glycosylation. 26405108 5 30 theme Hag 798:800 arg1 PAV_2c01710 811:821 PAV_2c01710 811:821 PAV_2c01710 811:821 Analysis on purified flagellin demonstrated that the 30-kDa Hag protein (PAV_2c01710) is modified with an O-linked trisaccharide comprised of one hexose and two N-acetyl-hexosamine residues, at three sites of glycosylation. 26405108 7 31 theme defective 1175:1183 arg1 Mutants 1167:1173 Mutants 1167:1173 Mutants defective in these genes 1167:1198 Mutants defective in these genes exhibited altered migration in sodium dodecyl sulfate polyacrylamide gel electrophoresis as well as loss of extracellular flagella production and bacterial motility. 26405108 0 32 gly glycosylation 10:22 arg1 CCM 47:49 Paenibacillus alvei CCM 27:49 Paenibacillus alvei CCM 27:49 Flagellin glycosylation in Paenibacillus alvei CCM 2051T. 26405108 8 33 theme well-investigated 1625:1641 arg1 pathway 1676:1682 the well-investigated S-layer tyrosine O-glycosylation pathway 1621:1682 the well-investigated S-layer tyrosine O-glycosylation pathway 1621:1682 This study reveals that flagellin glycosylation in P. alvei is pivotal to flagella formation and bacterial motility in vivo, and simultaneously identifies flagella glycosylation as a second protein O-glycosylation system in this bacterium, in addition to the well-investigated S-layer tyrosine O-glycosylation pathway. 26405108 3 34 theme protein 653:659 arg1 Hag 661:663 the flagellin protein Hag 639:663 the flagellin protein Hag 639:663 Paenibacillus alvei CCM 2051(T) swarms vigorously on solidified culture medium, with swarming relying on functional flagella as evidenced by abolished biofilm formation of a non-motile P. alvei mutant defective in the flagellin protein Hag. 26405108 2 35 theme secondary 352:360 arg1 alvei 343:347 Paenibacillus alvei 329:347 Paenibacillus alvei 329:347 The basis of flagellin glycosylation has been studied for various Gram-negative bacteria, but less is known about flagellin glycans of Gram-positive bacteria including Paenibacillus alvei, a secondary invader of honeybee colonies diseased with European foulbrood. 26405108 2 35 theme secondary 352:360 arg1 invader 362:368 a secondary invader 350:368 a secondary invader of honeybee colonies diseased with European foulbrood 350:422 The basis of flagellin glycosylation has been studied for various Gram-negative bacteria, but less is known about flagellin glycans of Gram-positive bacteria including Paenibacillus alvei, a secondary invader of honeybee colonies diseased with European foulbrood. 26405108 6 36 theme flagellin 1135:1143 arg1 island 1159:1164 a flagellin glycosylation island 1133:1164 a flagellin glycosylation island 1133:1164 Downstream of the hag gene on the bacterial chromosome, two open reading frames (PAV_2c01630, PAV_2c01640) encoding putative glycosyltransferases were shown to constitute a flagellin glycosylation island. 26405108 8 37 theme tyrosine 1651:1658 arg1 pathway 1676:1682 the well-investigated S-layer tyrosine O-glycosylation pathway 1621:1682 the well-investigated S-layer tyrosine O-glycosylation pathway 1621:1682 This study reveals that flagellin glycosylation in P. alvei is pivotal to flagella formation and bacterial motility in vivo, and simultaneously identifies flagella glycosylation as a second protein O-glycosylation system in this bacterium, in addition to the well-investigated S-layer tyrosine O-glycosylation pathway. 26405108 3 38 theme culture 489:495 arg1 medium 497:502 solidified culture medium 478:502 solidified culture medium 478:502 Paenibacillus alvei CCM 2051(T) swarms vigorously on solidified culture medium, with swarming relying on functional flagella as evidenced by abolished biofilm formation of a non-motile P. alvei mutant defective in the flagellin protein Hag. 26405108 8 39 from glycosylation 1400:1412 arg1 alvei 1420:1424 P. alvei 1417:1424 P. alvei 1417:1424 This study reveals that flagellin glycosylation in P. alvei is pivotal to flagella formation and bacterial motility in vivo, and simultaneously identifies flagella glycosylation as a second protein O-glycosylation system in this bacterium, in addition to the well-investigated S-layer tyrosine O-glycosylation pathway. 26405108 2 40 theme colonies 382:389 arg1 alvei 343:347 Paenibacillus alvei 329:347 Paenibacillus alvei 329:347 The basis of flagellin glycosylation has been studied for various Gram-negative bacteria, but less is known about flagellin glycans of Gram-positive bacteria including Paenibacillus alvei, a secondary invader of honeybee colonies diseased with European foulbrood. 26405108 2 40 theme colonies 382:389 arg1 invader 362:368 a secondary invader 350:368 a secondary invader of honeybee colonies diseased with European foulbrood 350:422 The basis of flagellin glycosylation has been studied for various Gram-negative bacteria, but less is known about flagellin glycans of Gram-positive bacteria including Paenibacillus alvei, a secondary invader of honeybee colonies diseased with European foulbrood. 26405108 3 41 from relying 519:525 arg1 flagella 541:548 functional flagella 530:548 functional flagella as evidenced by abolished biofilm formation of a non-motile P. alvei mutant defective in the flagellin protein Hag 530:663 Paenibacillus alvei CCM 2051(T) swarms vigorously on solidified culture medium, with swarming relying on functional flagella as evidenced by abolished biofilm formation of a non-motile P. alvei mutant defective in the flagellin protein Hag. 26405108 3 42 from Hag 661:663 arg1 defective 626:634 defective 626:634 defective 626:634 Paenibacillus alvei CCM 2051(T) swarms vigorously on solidified culture medium, with swarming relying on functional flagella as evidenced by abolished biofilm formation of a non-motile P. alvei mutant defective in the flagellin protein Hag. 26405108 6 43 theme glycosylation 1145:1157 arg1 island 1159:1164 a flagellin glycosylation island 1133:1164 a flagellin glycosylation island 1133:1164 Downstream of the hag gene on the bacterial chromosome, two open reading frames (PAV_2c01630, PAV_2c01640) encoding putative glycosyltransferases were shown to constitute a flagellin glycosylation island. 26405108 2 44 theme flagellin 275:283 arg1 glycans 285:291 flagellin glycans 275:291 flagellin glycans of Gram-positive bacteria including Paenibacillus alvei, a secondary invader of honeybee colonies diseased with European foulbrood 275:422 The basis of flagellin glycosylation has been studied for various Gram-negative bacteria, but less is known about flagellin glycans of Gram-positive bacteria including Paenibacillus alvei, a secondary invader of honeybee colonies diseased with European foulbrood. 26405108 5 45 mod modified 827:834 arg1 protein 802:808 the 30-kDa Hag protein 787:808 the 30-kDa Hag protein (PAV_2c01710) 787:822 Analysis on purified flagellin demonstrated that the 30-kDa Hag protein (PAV_2c01710) is modified with an O-linked trisaccharide comprised of one hexose and two N-acetyl-hexosamine residues, at three sites of glycosylation. 26405108 5 45 mod modified 827:834 arg3 trisaccharide 853:865 an O-linked trisaccharide 841:865 an O-linked trisaccharide comprised of one hexose and two N-acetyl-hexosamine residues 841:926 Analysis on purified flagellin demonstrated that the 30-kDa Hag protein (PAV_2c01710) is modified with an O-linked trisaccharide comprised of one hexose and two N-acetyl-hexosamine residues, at three sites of glycosylation. 26405108 5 45 mod modified 827:834 arg1 PAV_2c01710 811:821 PAV_2c01710 811:821 PAV_2c01710 811:821 Analysis on purified flagellin demonstrated that the 30-kDa Hag protein (PAV_2c01710) is modified with an O-linked trisaccharide comprised of one hexose and two N-acetyl-hexosamine residues, at three sites of glycosylation. 26405108 3 46 dep P. 610:611 arg1 alvei 613:617 alvei 613:617 alvei 613:617 Paenibacillus alvei CCM 2051(T) swarms vigorously on solidified culture medium, with swarming relying on functional flagella as evidenced by abolished biofilm formation of a non-motile P. alvei mutant defective in the flagellin protein Hag. 26405108 6 47 theme gene 984:987 arg1 Downstream 962:971 Downstream 962:971 Downstream 962:971 Downstream of the hag gene on the bacterial chromosome, two open reading frames (PAV_2c01630, PAV_2c01640) encoding putative glycosyltransferases were shown to constitute a flagellin glycosylation island. 26405108 3 48 theme abolished 566:574 arg1 formation 584:592 abolished biofilm formation 566:592 abolished biofilm formation of a non-motile P. alvei mutant defective in the flagellin protein Hag 566:663 Paenibacillus alvei CCM 2051(T) swarms vigorously on solidified culture medium, with swarming relying on functional flagella as evidenced by abolished biofilm formation of a non-motile P. alvei mutant defective in the flagellin protein Hag. 26405108 7 49 theme flagella 1322:1329 arg1 production 1331:1340 extracellular flagella production 1308:1340 extracellular flagella production 1308:1340 Mutants defective in these genes exhibited altered migration in sodium dodecyl sulfate polyacrylamide gel electrophoresis as well as loss of extracellular flagella production and bacterial motility. 26405108 3 50 theme P. 610:611 arg1 mutant 619:624 a non-motile P. alvei mutant 597:624 a non-motile P. alvei mutant defective in the flagellin protein Hag 597:663 Paenibacillus alvei CCM 2051(T) swarms vigorously on solidified culture medium, with swarming relying on functional flagella as evidenced by abolished biofilm formation of a non-motile P. alvei mutant defective in the flagellin protein Hag. 26405108 5 51 theme O-linked 844:851 arg1 trisaccharide 853:865 an O-linked trisaccharide 841:865 an O-linked trisaccharide comprised of one hexose and two N-acetyl-hexosamine residues 841:926 Analysis on purified flagellin demonstrated that the 30-kDa Hag protein (PAV_2c01710) is modified with an O-linked trisaccharide comprised of one hexose and two N-acetyl-hexosamine residues, at three sites of glycosylation. 26405108 5 52 from Analysis 738:745 arg1 flagellin 759:767 purified flagellin 750:767 purified flagellin 750:767 Analysis on purified flagellin demonstrated that the 30-kDa Hag protein (PAV_2c01710) is modified with an O-linked trisaccharide comprised of one hexose and two N-acetyl-hexosamine residues, at three sites of glycosylation. 26405108 2 53 theme Gram-negative 227:239 arg1 bacteria 241:248 various Gram-negative bacteria 219:248 various Gram-negative bacteria 219:248 The basis of flagellin glycosylation has been studied for various Gram-negative bacteria, but less is known about flagellin glycans of Gram-positive bacteria including Paenibacillus alvei, a secondary invader of honeybee colonies diseased with European foulbrood. 26405108 3 54 dep flagella 541:548 arg1 evidenced 553:561 evidenced 553:561 evidenced by abolished biofilm formation of a non-motile P. alvei mutant defective in the flagellin protein Hag 553:663 Paenibacillus alvei CCM 2051(T) swarms vigorously on solidified culture medium, with swarming relying on functional flagella as evidenced by abolished biofilm formation of a non-motile P. alvei mutant defective in the flagellin protein Hag. 26405108 7 55 from defective 1175:1183 arg1 genes 1194:1198 these genes 1188:1198 these genes 1188:1198 Mutants defective in these genes exhibited altered migration in sodium dodecyl sulfate polyacrylamide gel electrophoresis as well as loss of extracellular flagella production and bacterial motility. 26405108 4 56 theme alvei 705:709 arg1 flagella 711:718 the polar P. alvei flagella 692:718 the polar P. alvei flagella 692:718 Here, the glycobiology of the polar P. alvei flagella was investigated. 26405108 2 57 theme bacteria 310:317 arg1 glycans 285:291 flagellin glycans 275:291 flagellin glycans of Gram-positive bacteria including Paenibacillus alvei, a secondary invader of honeybee colonies diseased with European foulbrood 275:422 The basis of flagellin glycosylation has been studied for various Gram-negative bacteria, but less is known about flagellin glycans of Gram-positive bacteria including Paenibacillus alvei, a secondary invader of honeybee colonies diseased with European foulbrood. 26405108 6 58 theme reading 1027:1033 arg1 frames 1035:1040 two open reading frames 1018:1040 two open reading frames (PAV_2c01630, PAV_2c01640) encoding putative glycosyltransferases 1018:1106 Downstream of the hag gene on the bacterial chromosome, two open reading frames (PAV_2c01630, PAV_2c01640) encoding putative glycosyltransferases were shown to constitute a flagellin glycosylation island. 26405108 7 59 theme polyacrylamide 1254:1267 arg1 electrophoresis 1273:1287 sodium dodecyl sulfate polyacrylamide gel electrophoresis 1231:1287 sodium dodecyl sulfate polyacrylamide gel electrophoresis as well as loss of extracellular flagella production and bacterial motility 1231:1363 Mutants defective in these genes exhibited altered migration in sodium dodecyl sulfate polyacrylamide gel electrophoresis as well as loss of extracellular flagella production and bacterial motility. 26405108 3 60 theme mutant 619:624 arg1 formation 584:592 abolished biofilm formation 566:592 abolished biofilm formation of a non-motile P. alvei mutant defective in the flagellin protein Hag 566:663 Paenibacillus alvei CCM 2051(T) swarms vigorously on solidified culture medium, with swarming relying on functional flagella as evidenced by abolished biofilm formation of a non-motile P. alvei mutant defective in the flagellin protein Hag. 26405108 1 61 theme bacterial 141:149 arg1 flagella 151:158 bacterial flagella 141:158 bacterial flagella 141:158 Flagellin glycosylation impacts, in several documented cases, the functionality of bacterial flagella. 26405108 8 62 theme protein 1556:1562 arg1 glycosylation 1530:1542 flagella glycosylation 1521:1542 flagella glycosylation 1521:1542 This study reveals that flagellin glycosylation in P. alvei is pivotal to flagella formation and bacterial motility in vivo, and simultaneously identifies flagella glycosylation as a second protein O-glycosylation system in this bacterium, in addition to the well-investigated S-layer tyrosine O-glycosylation pathway. 26405108 8 62 theme protein 1556:1562 arg1 system 1580:1585 a second protein O-glycosylation system 1547:1585 a second protein O-glycosylation system in this bacterium 1547:1603 This study reveals that flagellin glycosylation in P. alvei is pivotal to flagella formation and bacterial motility in vivo, and simultaneously identifies flagella glycosylation as a second protein O-glycosylation system in this bacterium, in addition to the well-investigated S-layer tyrosine O-glycosylation pathway. 26405108 7 63 theme dodecyl 1238:1244 arg1 electrophoresis 1273:1287 sodium dodecyl sulfate polyacrylamide gel electrophoresis 1231:1287 sodium dodecyl sulfate polyacrylamide gel electrophoresis as well as loss of extracellular flagella production and bacterial motility 1231:1363 Mutants defective in these genes exhibited altered migration in sodium dodecyl sulfate polyacrylamide gel electrophoresis as well as loss of extracellular flagella production and bacterial motility. 26405108 5 64 link O-linked 844:851 arg1 trisaccharide 853:865 an O-linked trisaccharide 841:865 an O-linked trisaccharide comprised of one hexose and two N-acetyl-hexosamine residues 841:926 Analysis on purified flagellin demonstrated that the 30-kDa Hag protein (PAV_2c01710) is modified with an O-linked trisaccharide comprised of one hexose and two N-acetyl-hexosamine residues, at three sites of glycosylation. 26405108 5 65 theme N-acetyl-hexosamine 899:917 arg1 residues 919:926 two N-acetyl-hexosamine residues 895:926 two N-acetyl-hexosamine residues 895:926 Analysis on purified flagellin demonstrated that the 30-kDa Hag protein (PAV_2c01710) is modified with an O-linked trisaccharide comprised of one hexose and two N-acetyl-hexosamine residues, at three sites of glycosylation. 26405108 0 66 from glycosylation 10:22 arg1 CCM 47:49 Paenibacillus alvei CCM 27:49 Paenibacillus alvei CCM 27:49 Flagellin glycosylation in Paenibacillus alvei CCM 2051T. 26405108 4 67 theme polar 696:700 arg1 flagella 711:718 the polar P. alvei flagella 692:718 the polar P. alvei flagella 692:718 Here, the glycobiology of the polar P. alvei flagella was investigated. 26405108 1 68 theme Flagellin 58:66 arg1 glycosylation 68:80 Flagellin glycosylation 58:80 Flagellin glycosylation 58:80 Flagellin glycosylation impacts, in several documented cases, the functionality of bacterial flagella. 26405108 2 69 theme Gram-positive 296:308 arg1 bacteria 310:317 Gram-positive bacteria 296:317 Gram-positive bacteria including Paenibacillus alvei, a secondary invader of honeybee colonies diseased with European foulbrood 296:422 The basis of flagellin glycosylation has been studied for various Gram-negative bacteria, but less is known about flagellin glycans of Gram-positive bacteria including Paenibacillus alvei, a secondary invader of honeybee colonies diseased with European foulbrood. 26405108 2 69 theme Gram-positive 296:308 arg1 alvei 343:347 Paenibacillus alvei 329:347 Paenibacillus alvei 329:347 The basis of flagellin glycosylation has been studied for various Gram-negative bacteria, but less is known about flagellin glycans of Gram-positive bacteria including Paenibacillus alvei, a secondary invader of honeybee colonies diseased with European foulbrood. 26405108 6 70 dep frames 1035:1040 arg1 PAV_2c01630 1043:1053 PAV_2c01630 1043:1053 PAV_2c01630 1043:1053 Downstream of the hag gene on the bacterial chromosome, two open reading frames (PAV_2c01630, PAV_2c01640) encoding putative glycosyltransferases were shown to constitute a flagellin glycosylation island. 26405108 7 71 theme altered 1210:1216 arg1 migration 1218:1226 altered migration 1210:1226 altered migration 1210:1226 Mutants defective in these genes exhibited altered migration in sodium dodecyl sulfate polyacrylamide gel electrophoresis as well as loss of extracellular flagella production and bacterial motility. 26405108 6 72 theme putative 1078:1085 arg1 glycosyltransferases 1087:1106 putative glycosyltransferases 1078:1106 putative glycosyltransferases 1078:1106 Downstream of the hag gene on the bacterial chromosome, two open reading frames (PAV_2c01630, PAV_2c01640) encoding putative glycosyltransferases were shown to constitute a flagellin glycosylation island. 26405108 7 73 from genes 1194:1198 arg1 defective 1175:1183 defective 1175:1183 defective 1175:1183 Mutants defective in these genes exhibited altered migration in sodium dodecyl sulfate polyacrylamide gel electrophoresis as well as loss of extracellular flagella production and bacterial motility. 26405108 2 74 theme European 405:412 arg1 foulbrood 414:422 European foulbrood 405:422 European foulbrood 405:422 The basis of flagellin glycosylation has been studied for various Gram-negative bacteria, but less is known about flagellin glycans of Gram-positive bacteria including Paenibacillus alvei, a secondary invader of honeybee colonies diseased with European foulbrood. 26405108 8 75 from system 1580:1585 arg1 bacterium 1595:1603 this bacterium 1590:1603 this bacterium 1590:1603 This study reveals that flagellin glycosylation in P. alvei is pivotal to flagella formation and bacterial motility in vivo, and simultaneously identifies flagella glycosylation as a second protein O-glycosylation system in this bacterium, in addition to the well-investigated S-layer tyrosine O-glycosylation pathway. 26405108 8 76 dep pathway 1676:1682 arg1 addition 1609:1616 addition 1609:1616 addition 1609:1616 This study reveals that flagellin glycosylation in P. alvei is pivotal to flagella formation and bacterial motility in vivo, and simultaneously identifies flagella glycosylation as a second protein O-glycosylation system in this bacterium, in addition to the well-investigated S-layer tyrosine O-glycosylation pathway. 26405108 0 77 theme Paenibacillus 27:39 arg1 CCM 47:49 Paenibacillus alvei CCM 27:49 Paenibacillus alvei CCM 27:49 Flagellin glycosylation in Paenibacillus alvei CCM 2051T. 26405108 1 78 theme documented 102:111 arg1 cases 113:117 several documented cases 94:117 several documented cases 94:117 Flagellin glycosylation impacts, in several documented cases, the functionality of bacterial flagella. 26405108 7 79 theme bacterial 1346:1354 arg1 motility 1356:1363 bacterial motility 1346:1363 bacterial motility 1346:1363 Mutants defective in these genes exhibited altered migration in sodium dodecyl sulfate polyacrylamide gel electrophoresis as well as loss of extracellular flagella production and bacterial motility. 26405108 2 80 theme glycosylation 184:196 arg1 basis 165:169 The basis 161:169 The basis of flagellin glycosylation 161:196 The basis of flagellin glycosylation has been studied for various Gram-negative bacteria, but less is known about flagellin glycans of Gram-positive bacteria including Paenibacillus alvei, a secondary invader of honeybee colonies diseased with European foulbrood. 26405108 3 81 theme solidified 478:487 arg1 medium 497:502 solidified culture medium 478:502 solidified culture medium 478:502 Paenibacillus alvei CCM 2051(T) swarms vigorously on solidified culture medium, with swarming relying on functional flagella as evidenced by abolished biofilm formation of a non-motile P. alvei mutant defective in the flagellin protein Hag. 26405108 5 82 theme 30-kDa 791:796 arg1 protein 802:808 the 30-kDa Hag protein 787:808 the 30-kDa Hag protein (PAV_2c01710) 787:822 Analysis on purified flagellin demonstrated that the 30-kDa Hag protein (PAV_2c01710) is modified with an O-linked trisaccharide comprised of one hexose and two N-acetyl-hexosamine residues, at three sites of glycosylation. 26405108 5 82 theme 30-kDa 791:796 arg1 PAV_2c01710 811:821 PAV_2c01710 811:821 PAV_2c01710 811:821 Analysis on purified flagellin demonstrated that the 30-kDa Hag protein (PAV_2c01710) is modified with an O-linked trisaccharide comprised of one hexose and two N-acetyl-hexosamine residues, at three sites of glycosylation. 26405108 7 83 theme production 1331:1340 arg1 electrophoresis 1273:1287 sodium dodecyl sulfate polyacrylamide gel electrophoresis 1231:1287 sodium dodecyl sulfate polyacrylamide gel electrophoresis as well as loss of extracellular flagella production and bacterial motility 1231:1363 Mutants defective in these genes exhibited altered migration in sodium dodecyl sulfate polyacrylamide gel electrophoresis as well as loss of extracellular flagella production and bacterial motility. 26405108 7 83 theme production 1331:1340 arg1 loss 1300:1303 loss 1300:1303 sodium dodecyl sulfate polyacrylamide gel electrophoresis as well as loss of extracellular flagella production and bacterial motility 1231:1363 Mutants defective in these genes exhibited altered migration in sodium dodecyl sulfate polyacrylamide gel electrophoresis as well as loss of extracellular flagella production and bacterial motility. 26405108 3 84 theme CCM 445:447 arg1 T 454:454 T 454:454 T 454:454 Paenibacillus alvei CCM 2051(T) swarms vigorously on solidified culture medium, with swarming relying on functional flagella as evidenced by abolished biofilm formation of a non-motile P. alvei mutant defective in the flagellin protein Hag. 26405108 3 84 theme CCM 445:447 arg1 2051 449:452 Paenibacillus alvei CCM 2051 425:452 Paenibacillus alvei CCM 2051(T) 425:455 Paenibacillus alvei CCM 2051(T) swarms vigorously on solidified culture medium, with swarming relying on functional flagella as evidenced by abolished biofilm formation of a non-motile P. alvei mutant defective in the flagellin protein Hag. 26405108 8 85 theme S-layer 1643:1649 arg1 pathway 1676:1682 the well-investigated S-layer tyrosine O-glycosylation pathway 1621:1682 the well-investigated S-layer tyrosine O-glycosylation pathway 1621:1682 This study reveals that flagellin glycosylation in P. alvei is pivotal to flagella formation and bacterial motility in vivo, and simultaneously identifies flagella glycosylation as a second protein O-glycosylation system in this bacterium, in addition to the well-investigated S-layer tyrosine O-glycosylation pathway. 26405108 3 86 theme flagellin 643:651 arg1 Hag 661:663 the flagellin protein Hag 639:663 the flagellin protein Hag 639:663 Paenibacillus alvei CCM 2051(T) swarms vigorously on solidified culture medium, with swarming relying on functional flagella as evidenced by abolished biofilm formation of a non-motile P. alvei mutant defective in the flagellin protein Hag. 26405108 7 87 theme extracellular 1308:1320 arg1 production 1331:1340 extracellular flagella production 1308:1340 extracellular flagella production 1308:1340 Mutants defective in these genes exhibited altered migration in sodium dodecyl sulfate polyacrylamide gel electrophoresis as well as loss of extracellular flagella production and bacterial motility. 26405108 3 88 theme Paenibacillus 425:437 arg1 T 454:454 T 454:454 T 454:454 Paenibacillus alvei CCM 2051(T) swarms vigorously on solidified culture medium, with swarming relying on functional flagella as evidenced by abolished biofilm formation of a non-motile P. alvei mutant defective in the flagellin protein Hag. 26405108 3 88 theme Paenibacillus 425:437 arg1 2051 449:452 Paenibacillus alvei CCM 2051 425:452 Paenibacillus alvei CCM 2051(T) 425:455 Paenibacillus alvei CCM 2051(T) swarms vigorously on solidified culture medium, with swarming relying on functional flagella as evidenced by abolished biofilm formation of a non-motile P. alvei mutant defective in the flagellin protein Hag. 26405108 8 89 theme O-glycosylation 1660:1674 arg1 pathway 1676:1682 the well-investigated S-layer tyrosine O-glycosylation pathway 1621:1682 the well-investigated S-layer tyrosine O-glycosylation pathway 1621:1682 This study reveals that flagellin glycosylation in P. alvei is pivotal to flagella formation and bacterial motility in vivo, and simultaneously identifies flagella glycosylation as a second protein O-glycosylation system in this bacterium, in addition to the well-investigated S-layer tyrosine O-glycosylation pathway. 26405108 8 90 theme bacterial 1463:1471 arg1 motility 1473:1480 bacterial motility 1463:1480 bacterial motility 1463:1480 This study reveals that flagellin glycosylation in P. alvei is pivotal to flagella formation and bacterial motility in vivo, and simultaneously identifies flagella glycosylation as a second protein O-glycosylation system in this bacterium, in addition to the well-investigated S-layer tyrosine O-glycosylation pathway. 26405108 2 91 theme honeybee 373:380 arg1 colonies 382:389 honeybee colonies 373:389 honeybee colonies diseased with European foulbrood 373:422 The basis of flagellin glycosylation has been studied for various Gram-negative bacteria, but less is known about flagellin glycans of Gram-positive bacteria including Paenibacillus alvei, a secondary invader of honeybee colonies diseased with European foulbrood. 26405108 3 92 theme functional 530:539 arg1 flagella 541:548 functional flagella 530:548 functional flagella as evidenced by abolished biofilm formation of a non-motile P. alvei mutant defective in the flagellin protein Hag 530:663 Paenibacillus alvei CCM 2051(T) swarms vigorously on solidified culture medium, with swarming relying on functional flagella as evidenced by abolished biofilm formation of a non-motile P. alvei mutant defective in the flagellin protein Hag. 26260330 4 0 theme conjunctival 491:502 arg1 IOBA-NHC 515:522 IOBA-NHC 515:522 IOBA-NHC 515:522 This study employed a spontaneously immortalized normal human conjunctival cell line, IOBA-NHC, as a model to investigate hyperosmotic stress-induced changes of metabolites and proteins. 26260330 4 0 theme conjunctival 491:502 arg1 line 509:512 normal human conjunctival cell line 478:512 normal human conjunctival cell line 478:512 This study employed a spontaneously immortalized normal human conjunctival cell line, IOBA-NHC, as a model to investigate hyperosmotic stress-induced changes of metabolites and proteins. 26260330 4 0 theme conjunctival 491:502 arg1 model 530:534 a model 528:534 a model to investigate hyperosmotic stress-induced changes of metabolites and proteins 528:613 This study employed a spontaneously immortalized normal human conjunctival cell line, IOBA-NHC, as a model to investigate hyperosmotic stress-induced changes of metabolites and proteins. 26260330 4 1 theme normal 478:483 arg1 IOBA-NHC 515:522 IOBA-NHC 515:522 IOBA-NHC 515:522 This study employed a spontaneously immortalized normal human conjunctival cell line, IOBA-NHC, as a model to investigate hyperosmotic stress-induced changes of metabolites and proteins. 26260330 4 1 theme normal 478:483 arg1 line 509:512 normal human conjunctival cell line 478:512 normal human conjunctival cell line 478:512 This study employed a spontaneously immortalized normal human conjunctival cell line, IOBA-NHC, as a model to investigate hyperosmotic stress-induced changes of metabolites and proteins. 26260330 4 1 theme normal 478:483 arg1 model 530:534 a model 528:534 a model to investigate hyperosmotic stress-induced changes of metabolites and proteins 528:613 This study employed a spontaneously immortalized normal human conjunctival cell line, IOBA-NHC, as a model to investigate hyperosmotic stress-induced changes of metabolites and proteins. 26260330 8 2 theme eye 1400:1402 arg1 markers 1385:1391 metabolite markers 1374:1391 metabolite markers of dry eye 1374:1402 These findings extend the current knowledge in metabolite markers of dry eye and provide potential therapeutic targets for its treatment. 26260330 3 3 theme dry 313:315 arg1 eye 317:319 dry eye 313:319 dry eye 313:319 Recent research efforts on dry eye have been directed toward biomarker discovery for diagnosis, response to treatment, and disease mechanisms. 26260330 5 4 dep h. 793:794 arg1 showed 861:866 showed 861:866 showed significant changes under at least one hyperosmotic stress treatment as compared with controls 861:961 Global and targeted metabonomic analyses as well as proteomic analysis were performed on IOBA-NHC cells incubated in serum-free media at 280 (control), 380, and 480 mOsm for 24 h. Twenty-one metabolites and seventy-six iTRAQ-identified proteins showed significant changes under at least one hyperosmotic stress treatment as compared with controls. 26260330 6 5 theme hyperosmotic 1112:1123 arg1 stress 1125:1130 hyperosmotic stress 1112:1130 hyperosmotic stress 1112:1130 SWATH-based proteomic analysis further confirmed the involvement of inflammatory pathways such as prostaglandin 2 synthesis in IOBA-NHC cells under hyperosmotic stress. 26260330 4 6 theme stress-induced 564:577 arg1 changes 579:585 hyperosmotic stress-induced changes 551:585 hyperosmotic stress-induced changes of metabolites and proteins 551:613 This study employed a spontaneously immortalized normal human conjunctival cell line, IOBA-NHC, as a model to investigate hyperosmotic stress-induced changes of metabolites and proteins. 26260330 5 7 theme serum-free 733:742 arg1 media 744:748 serum-free media 733:748 serum-free media 733:748 Global and targeted metabonomic analyses as well as proteomic analysis were performed on IOBA-NHC cells incubated in serum-free media at 280 (control), 380, and 480 mOsm for 24 h. Twenty-one metabolites and seventy-six iTRAQ-identified proteins showed significant changes under at least one hyperosmotic stress treatment as compared with controls. 26260330 8 8 from knowledge 1361:1369 arg1 markers 1385:1391 metabolite markers 1374:1391 metabolite markers of dry eye 1374:1402 These findings extend the current knowledge in metabolite markers of dry eye and provide potential therapeutic targets for its treatment. 26260330 4 9 theme metabolites 590:600 arg1 changes 579:585 hyperosmotic stress-induced changes 551:585 hyperosmotic stress-induced changes of metabolites and proteins 551:613 This study employed a spontaneously immortalized normal human conjunctival cell line, IOBA-NHC, as a model to investigate hyperosmotic stress-induced changes of metabolites and proteins. 26260330 3 10 theme biomarker 347:355 arg1 discovery 357:365 biomarker discovery 347:365 biomarker discovery for diagnosis, response to treatment, and disease mechanisms 347:426 Recent research efforts on dry eye have been directed toward biomarker discovery for diagnosis, response to treatment, and disease mechanisms. 26260330 4 11 theme immortalized 465:476 arg1 IOBA-NHC 515:522 IOBA-NHC 515:522 IOBA-NHC 515:522 This study employed a spontaneously immortalized normal human conjunctival cell line, IOBA-NHC, as a model to investigate hyperosmotic stress-induced changes of metabolites and proteins. 26260330 4 11 theme immortalized 465:476 arg1 line 509:512 normal human conjunctival cell line 478:512 normal human conjunctival cell line 478:512 This study employed a spontaneously immortalized normal human conjunctival cell line, IOBA-NHC, as a model to investigate hyperosmotic stress-induced changes of metabolites and proteins. 26260330 4 11 theme immortalized 465:476 arg1 model 530:534 a model 528:534 a model to investigate hyperosmotic stress-induced changes of metabolites and proteins 528:613 This study employed a spontaneously immortalized normal human conjunctival cell line, IOBA-NHC, as a model to investigate hyperosmotic stress-induced changes of metabolites and proteins. 26260330 5 12 theme proteomic 668:676 arg1 analysis 678:685 proteomic analysis 668:685 Global and targeted metabonomic analyses as well as proteomic analysis 616:685 Global and targeted metabonomic analyses as well as proteomic analysis were performed on IOBA-NHC cells incubated in serum-free media at 280 (control), 380, and 480 mOsm for 24 h. Twenty-one metabolites and seventy-six iTRAQ-identified proteins showed significant changes under at least one hyperosmotic stress treatment as compared with controls. 26260330 7 13 theme hyperosmotic 1306:1317 arg1 stress 1319:1324 hyperosmotic stress 1306:1324 hyperosmotic stress 1306:1324 This study is the first to identify glycerophosphocholine synthesis and O-linked β-N-acetylglucosamine glycosylation as key activated pathways in ocular surface cells under hyperosmotic stress. 26260330 2 14 theme cell 273:276 arg1 damage 278:283 cell damage 273:283 cell damage 273:283 Tear hyperosmolarity in dry eye contributes to inflammation and cell damage. 26260330 5 15 theme Global 616:621 arg1 analyses 648:655 Global and targeted metabonomic analyses 616:655 Global and targeted metabonomic analyses as well as proteomic analysis 616:685 Global and targeted metabonomic analyses as well as proteomic analysis were performed on IOBA-NHC cells incubated in serum-free media at 280 (control), 380, and 480 mOsm for 24 h. Twenty-one metabolites and seventy-six iTRAQ-identified proteins showed significant changes under at least one hyperosmotic stress treatment as compared with controls. 26260330 8 16 theme therapeutic 1426:1436 arg1 targets 1438:1444 potential therapeutic targets 1416:1444 potential therapeutic targets for its treatment 1416:1462 These findings extend the current knowledge in metabolite markers of dry eye and provide potential therapeutic targets for its treatment. 26260330 6 17 theme IOBA-NHC 1091:1098 arg1 cells 1100:1104 IOBA-NHC cells 1091:1104 IOBA-NHC cells 1091:1104 SWATH-based proteomic analysis further confirmed the involvement of inflammatory pathways such as prostaglandin 2 synthesis in IOBA-NHC cells under hyperosmotic stress. 26260330 5 18 theme iTRAQ-identified 835:850 arg1 proteins 852:859 seventy-six iTRAQ-identified proteins 823:859 seventy-six iTRAQ-identified proteins 823:859 Global and targeted metabonomic analyses as well as proteomic analysis were performed on IOBA-NHC cells incubated in serum-free media at 280 (control), 380, and 480 mOsm for 24 h. Twenty-one metabolites and seventy-six iTRAQ-identified proteins showed significant changes under at least one hyperosmotic stress treatment as compared with controls. 26260330 7 19 theme key 1253:1255 arg1 synthesis 1191:1199 glycerophosphocholine synthesis 1169:1199 glycerophosphocholine synthesis 1169:1199 This study is the first to identify glycerophosphocholine synthesis and O-linked β-N-acetylglucosamine glycosylation as key activated pathways in ocular surface cells under hyperosmotic stress. 26260330 7 19 theme key 1253:1255 arg1 pathways 1267:1274 key activated pathways 1253:1274 key activated pathways in ocular surface cells under hyperosmotic stress 1253:1324 This study is the first to identify glycerophosphocholine synthesis and O-linked β-N-acetylglucosamine glycosylation as key activated pathways in ocular surface cells under hyperosmotic stress. 26260330 7 19 theme key 1253:1255 arg1 glycosylation 1236:1248 O-linked β-N-acetylglucosamine glycosylation 1205:1248 O-linked β-N-acetylglucosamine glycosylation 1205:1248 This study is the first to identify glycerophosphocholine synthesis and O-linked β-N-acetylglucosamine glycosylation as key activated pathways in ocular surface cells under hyperosmotic stress. 26260330 4 20 theme human 485:489 arg1 IOBA-NHC 515:522 IOBA-NHC 515:522 IOBA-NHC 515:522 This study employed a spontaneously immortalized normal human conjunctival cell line, IOBA-NHC, as a model to investigate hyperosmotic stress-induced changes of metabolites and proteins. 26260330 4 20 theme human 485:489 arg1 line 509:512 normal human conjunctival cell line 478:512 normal human conjunctival cell line 478:512 This study employed a spontaneously immortalized normal human conjunctival cell line, IOBA-NHC, as a model to investigate hyperosmotic stress-induced changes of metabolites and proteins. 26260330 4 20 theme human 485:489 arg1 model 530:534 a model 528:534 a model to investigate hyperosmotic stress-induced changes of metabolites and proteins 528:613 This study employed a spontaneously immortalized normal human conjunctival cell line, IOBA-NHC, as a model to investigate hyperosmotic stress-induced changes of metabolites and proteins. 26260330 5 21 theme targeted 627:634 arg1 analyses 648:655 Global and targeted metabonomic analyses 616:655 Global and targeted metabonomic analyses as well as proteomic analysis 616:685 Global and targeted metabonomic analyses as well as proteomic analysis were performed on IOBA-NHC cells incubated in serum-free media at 280 (control), 380, and 480 mOsm for 24 h. Twenty-one metabolites and seventy-six iTRAQ-identified proteins showed significant changes under at least one hyperosmotic stress treatment as compared with controls. 26260330 8 22 theme potential 1416:1424 arg1 targets 1438:1444 potential therapeutic targets 1416:1444 potential therapeutic targets for its treatment 1416:1462 These findings extend the current knowledge in metabolite markers of dry eye and provide potential therapeutic targets for its treatment. 26260330 1 23 theme multifactorial 143:156 arg1 disease 171:177 a multifactorial inflammatory disease 141:177 a multifactorial inflammatory disease affecting the ocular surface 141:206 "Dry eye" is a multifactorial inflammatory disease affecting the ocular surface. 26260330 1 23 theme multifactorial 143:156 arg1 " 136:136 "Dry eye" 128:136 "Dry eye" 128:136 "Dry eye" is a multifactorial inflammatory disease affecting the ocular surface. 26260330 0 24 theme Metabonomic 7:17 arg1 Analysis 33:40 Global Metabonomic and Proteomic Analysis 0:40 Global Metabonomic and Proteomic Analysis of Human Conjunctival Epithelial Cells (IOBA-NHC) in Response to Hyperosmotic Stress. 0:126 Global Metabonomic and Proteomic Analysis of Human Conjunctival Epithelial Cells (IOBA-NHC) in Response to Hyperosmotic Stress. 26260330 0 25 from Analysis 33:40 arg1 Response 95:102 Response 95:102 Response to Hyperosmotic Stress 95:125 Global Metabonomic and Proteomic Analysis of Human Conjunctival Epithelial Cells (IOBA-NHC) in Response to Hyperosmotic Stress. 26260330 5 26 theme metabonomic 636:646 arg1 analyses 648:655 Global and targeted metabonomic analyses 616:655 Global and targeted metabonomic analyses as well as proteomic analysis 616:685 Global and targeted metabonomic analyses as well as proteomic analysis were performed on IOBA-NHC cells incubated in serum-free media at 280 (control), 380, and 480 mOsm for 24 h. Twenty-one metabolites and seventy-six iTRAQ-identified proteins showed significant changes under at least one hyperosmotic stress treatment as compared with controls. 26260330 7 27 theme surface 1286:1292 arg1 cells 1294:1298 ocular surface cells 1279:1298 ocular surface cells under hyperosmotic stress 1279:1324 This study is the first to identify glycerophosphocholine synthesis and O-linked β-N-acetylglucosamine glycosylation as key activated pathways in ocular surface cells under hyperosmotic stress. 26260330 2 28 from hyperosmolarity 214:228 arg1 eye 237:239 dry eye 233:239 dry eye 233:239 Tear hyperosmolarity in dry eye contributes to inflammation and cell damage. 26260330 1 29 theme inflammatory 158:169 arg1 disease 171:177 a multifactorial inflammatory disease 141:177 a multifactorial inflammatory disease affecting the ocular surface 141:206 "Dry eye" is a multifactorial inflammatory disease affecting the ocular surface. 26260330 1 29 theme inflammatory 158:169 arg1 " 136:136 "Dry eye" 128:136 "Dry eye" 128:136 "Dry eye" is a multifactorial inflammatory disease affecting the ocular surface. 26260330 0 30 theme Global 0:5 arg1 Analysis 33:40 Global Metabonomic and Proteomic Analysis 0:40 Global Metabonomic and Proteomic Analysis of Human Conjunctival Epithelial Cells (IOBA-NHC) in Response to Hyperosmotic Stress. 0:126 Global Metabonomic and Proteomic Analysis of Human Conjunctival Epithelial Cells (IOBA-NHC) in Response to Hyperosmotic Stress. 26260330 3 31 theme disease 409:415 arg1 mechanisms 417:426 disease mechanisms 409:426 disease mechanisms 409:426 Recent research efforts on dry eye have been directed toward biomarker discovery for diagnosis, response to treatment, and disease mechanisms. 26260330 0 32 theme Proteomic 23:31 arg1 Analysis 33:40 Global Metabonomic and Proteomic Analysis 0:40 Global Metabonomic and Proteomic Analysis of Human Conjunctival Epithelial Cells (IOBA-NHC) in Response to Hyperosmotic Stress. 0:126 Global Metabonomic and Proteomic Analysis of Human Conjunctival Epithelial Cells (IOBA-NHC) in Response to Hyperosmotic Stress. 26260330 6 33 theme proteomic 976:984 arg1 analysis 986:993 SWATH-based proteomic analysis 964:993 SWATH-based proteomic analysis 964:993 SWATH-based proteomic analysis further confirmed the involvement of inflammatory pathways such as prostaglandin 2 synthesis in IOBA-NHC cells under hyperosmotic stress. 26260330 5 34 theme IOBA-NHC 705:712 arg1 cells 714:718 IOBA-NHC cells 705:718 IOBA-NHC cells incubated in serum-free media at 280 (control), 380, and 480 mOsm for 24 h. Twenty-one metabolites and seventy-six iTRAQ-identified proteins showed significant changes under at least one hyperosmotic stress treatment as compared with controls 705:961 Global and targeted metabonomic analyses as well as proteomic analysis were performed on IOBA-NHC cells incubated in serum-free media at 280 (control), 380, and 480 mOsm for 24 h. Twenty-one metabolites and seventy-six iTRAQ-identified proteins showed significant changes under at least one hyperosmotic stress treatment as compared with controls. 26260330 8 35 theme dry 1396:1398 arg1 eye 1400:1402 dry eye 1396:1402 dry eye 1396:1402 These findings extend the current knowledge in metabolite markers of dry eye and provide potential therapeutic targets for its treatment. 26260330 5 36 theme Twenty-one 796:805 arg1 metabolites 807:817 Twenty-one metabolites 796:817 Twenty-one metabolites 796:817 Global and targeted metabonomic analyses as well as proteomic analysis were performed on IOBA-NHC cells incubated in serum-free media at 280 (control), 380, and 480 mOsm for 24 h. Twenty-one metabolites and seventy-six iTRAQ-identified proteins showed significant changes under at least one hyperosmotic stress treatment as compared with controls. 26260330 7 37 theme O-linked 1205:1212 arg1 synthesis 1191:1199 glycerophosphocholine synthesis 1169:1199 glycerophosphocholine synthesis 1169:1199 This study is the first to identify glycerophosphocholine synthesis and O-linked β-N-acetylglucosamine glycosylation as key activated pathways in ocular surface cells under hyperosmotic stress. 26260330 7 37 theme O-linked 1205:1212 arg1 pathways 1267:1274 key activated pathways 1253:1274 key activated pathways in ocular surface cells under hyperosmotic stress 1253:1324 This study is the first to identify glycerophosphocholine synthesis and O-linked β-N-acetylglucosamine glycosylation as key activated pathways in ocular surface cells under hyperosmotic stress. 26260330 7 37 theme O-linked 1205:1212 arg1 glycosylation 1236:1248 O-linked β-N-acetylglucosamine glycosylation 1205:1248 O-linked β-N-acetylglucosamine glycosylation 1205:1248 This study is the first to identify glycerophosphocholine synthesis and O-linked β-N-acetylglucosamine glycosylation as key activated pathways in ocular surface cells under hyperosmotic stress. 26260330 4 38 theme hyperosmotic 551:562 arg1 changes 579:585 hyperosmotic stress-induced changes 551:585 hyperosmotic stress-induced changes of metabolites and proteins 551:613 This study employed a spontaneously immortalized normal human conjunctival cell line, IOBA-NHC, as a model to investigate hyperosmotic stress-induced changes of metabolites and proteins. 26260330 0 39 theme Hyperosmotic 107:118 arg1 Stress 120:125 Hyperosmotic Stress 107:125 Hyperosmotic Stress 107:125 Global Metabonomic and Proteomic Analysis of Human Conjunctival Epithelial Cells (IOBA-NHC) in Response to Hyperosmotic Stress. 26260330 6 40 from involvement 1017:1027 arg1 cells 1100:1104 IOBA-NHC cells 1091:1104 IOBA-NHC cells 1091:1104 SWATH-based proteomic analysis further confirmed the involvement of inflammatory pathways such as prostaglandin 2 synthesis in IOBA-NHC cells under hyperosmotic stress. 26260330 7 41 theme glycerophosphocholine 1169:1189 arg1 pathways 1267:1274 key activated pathways 1253:1274 key activated pathways in ocular surface cells under hyperosmotic stress 1253:1324 This study is the first to identify glycerophosphocholine synthesis and O-linked β-N-acetylglucosamine glycosylation as key activated pathways in ocular surface cells under hyperosmotic stress. 26260330 7 41 theme glycerophosphocholine 1169:1189 arg1 synthesis 1191:1199 glycerophosphocholine synthesis 1169:1199 glycerophosphocholine synthesis 1169:1199 This study is the first to identify glycerophosphocholine synthesis and O-linked β-N-acetylglucosamine glycosylation as key activated pathways in ocular surface cells under hyperosmotic stress. 26260330 7 41 theme glycerophosphocholine 1169:1189 arg1 glycosylation 1236:1248 O-linked β-N-acetylglucosamine glycosylation 1205:1248 O-linked β-N-acetylglucosamine glycosylation 1205:1248 This study is the first to identify glycerophosphocholine synthesis and O-linked β-N-acetylglucosamine glycosylation as key activated pathways in ocular surface cells under hyperosmotic stress. 26260330 8 42 theme current 1353:1359 arg1 knowledge 1361:1369 the current knowledge 1349:1369 the current knowledge in metabolite markers of dry eye 1349:1402 These findings extend the current knowledge in metabolite markers of dry eye and provide potential therapeutic targets for its treatment. 26260330 6 43 theme prostaglandin 1062:1074 arg1 synthesis 1078:1086 prostaglandin 2 synthesis 1062:1086 prostaglandin 2 synthesis 1062:1086 SWATH-based proteomic analysis further confirmed the involvement of inflammatory pathways such as prostaglandin 2 synthesis in IOBA-NHC cells under hyperosmotic stress. 26260330 5 44 theme significant 868:878 arg1 changes 880:886 significant changes 868:886 significant changes 868:886 Global and targeted metabonomic analyses as well as proteomic analysis were performed on IOBA-NHC cells incubated in serum-free media at 280 (control), 380, and 480 mOsm for 24 h. Twenty-one metabolites and seventy-six iTRAQ-identified proteins showed significant changes under at least one hyperosmotic stress treatment as compared with controls. 26260330 1 45 theme ocular 193:198 arg1 surface 200:206 the ocular surface 189:206 the ocular surface 189:206 "Dry eye" is a multifactorial inflammatory disease affecting the ocular surface. 26260330 6 46 theme SWATH-based 964:974 arg1 analysis 986:993 SWATH-based proteomic analysis 964:993 SWATH-based proteomic analysis 964:993 SWATH-based proteomic analysis further confirmed the involvement of inflammatory pathways such as prostaglandin 2 synthesis in IOBA-NHC cells under hyperosmotic stress. 26260330 7 47 theme ocular 1279:1284 arg1 cells 1294:1298 ocular surface cells 1279:1298 ocular surface cells under hyperosmotic stress 1279:1324 This study is the first to identify glycerophosphocholine synthesis and O-linked β-N-acetylglucosamine glycosylation as key activated pathways in ocular surface cells under hyperosmotic stress. 26260330 5 48 theme seventy-six 823:833 arg1 proteins 852:859 seventy-six iTRAQ-identified proteins 823:859 seventy-six iTRAQ-identified proteins 823:859 Global and targeted metabonomic analyses as well as proteomic analysis were performed on IOBA-NHC cells incubated in serum-free media at 280 (control), 380, and 480 mOsm for 24 h. Twenty-one metabolites and seventy-six iTRAQ-identified proteins showed significant changes under at least one hyperosmotic stress treatment as compared with controls. 26260330 0 49 theme Conjunctival 51:62 arg1 IOBA-NHC 82:89 IOBA-NHC 82:89 IOBA-NHC 82:89 Global Metabonomic and Proteomic Analysis of Human Conjunctival Epithelial Cells (IOBA-NHC) in Response to Hyperosmotic Stress. 26260330 0 49 theme Conjunctival 51:62 arg1 Cells 75:79 Human Conjunctival Epithelial Cells 45:79 Human Conjunctival Epithelial Cells (IOBA-NHC) 45:90 Global Metabonomic and Proteomic Analysis of Human Conjunctival Epithelial Cells (IOBA-NHC) in Response to Hyperosmotic Stress. 26260330 7 50 theme activated 1257:1265 arg1 synthesis 1191:1199 glycerophosphocholine synthesis 1169:1199 glycerophosphocholine synthesis 1169:1199 This study is the first to identify glycerophosphocholine synthesis and O-linked β-N-acetylglucosamine glycosylation as key activated pathways in ocular surface cells under hyperosmotic stress. 26260330 7 50 theme activated 1257:1265 arg1 pathways 1267:1274 key activated pathways 1253:1274 key activated pathways in ocular surface cells under hyperosmotic stress 1253:1324 This study is the first to identify glycerophosphocholine synthesis and O-linked β-N-acetylglucosamine glycosylation as key activated pathways in ocular surface cells under hyperosmotic stress. 26260330 7 50 theme activated 1257:1265 arg1 glycosylation 1236:1248 O-linked β-N-acetylglucosamine glycosylation 1205:1248 O-linked β-N-acetylglucosamine glycosylation 1205:1248 This study is the first to identify glycerophosphocholine synthesis and O-linked β-N-acetylglucosamine glycosylation as key activated pathways in ocular surface cells under hyperosmotic stress. 26260330 3 51 theme research 293:300 arg1 efforts 302:308 Recent research efforts 286:308 Recent research efforts on dry eye 286:319 Recent research efforts on dry eye have been directed toward biomarker discovery for diagnosis, response to treatment, and disease mechanisms. 26260330 7 52 from pathways 1267:1274 arg1 cells 1294:1298 ocular surface cells 1279:1298 ocular surface cells under hyperosmotic stress 1279:1324 This study is the first to identify glycerophosphocholine synthesis and O-linked β-N-acetylglucosamine glycosylation as key activated pathways in ocular surface cells under hyperosmotic stress. 26260330 2 53 theme Tear 209:212 arg1 hyperosmolarity 214:228 Tear hyperosmolarity 209:228 Tear hyperosmolarity in dry eye 209:239 Tear hyperosmolarity in dry eye contributes to inflammation and cell damage. 26260330 0 54 theme Human 45:49 arg1 IOBA-NHC 82:89 IOBA-NHC 82:89 IOBA-NHC 82:89 Global Metabonomic and Proteomic Analysis of Human Conjunctival Epithelial Cells (IOBA-NHC) in Response to Hyperosmotic Stress. 26260330 0 54 theme Human 45:49 arg1 Cells 75:79 Human Conjunctival Epithelial Cells 45:79 Human Conjunctival Epithelial Cells (IOBA-NHC) 45:90 Global Metabonomic and Proteomic Analysis of Human Conjunctival Epithelial Cells (IOBA-NHC) in Response to Hyperosmotic Stress. 26260330 5 55 theme hyperosmotic 907:918 arg1 treatment 927:935 at least one hyperosmotic stress treatment 894:935 at least one hyperosmotic stress treatment 894:935 Global and targeted metabonomic analyses as well as proteomic analysis were performed on IOBA-NHC cells incubated in serum-free media at 280 (control), 380, and 480 mOsm for 24 h. Twenty-one metabolites and seventy-six iTRAQ-identified proteins showed significant changes under at least one hyperosmotic stress treatment as compared with controls. 26260330 7 56 theme β-N-acetylglucosamine 1214:1234 arg1 synthesis 1191:1199 glycerophosphocholine synthesis 1169:1199 glycerophosphocholine synthesis 1169:1199 This study is the first to identify glycerophosphocholine synthesis and O-linked β-N-acetylglucosamine glycosylation as key activated pathways in ocular surface cells under hyperosmotic stress. 26260330 7 56 theme β-N-acetylglucosamine 1214:1234 arg1 pathways 1267:1274 key activated pathways 1253:1274 key activated pathways in ocular surface cells under hyperosmotic stress 1253:1324 This study is the first to identify glycerophosphocholine synthesis and O-linked β-N-acetylglucosamine glycosylation as key activated pathways in ocular surface cells under hyperosmotic stress. 26260330 7 56 theme β-N-acetylglucosamine 1214:1234 arg1 glycosylation 1236:1248 O-linked β-N-acetylglucosamine glycosylation 1205:1248 O-linked β-N-acetylglucosamine glycosylation 1205:1248 This study is the first to identify glycerophosphocholine synthesis and O-linked β-N-acetylglucosamine glycosylation as key activated pathways in ocular surface cells under hyperosmotic stress. 26260330 5 57 theme stress 920:925 arg1 treatment 927:935 at least one hyperosmotic stress treatment 894:935 at least one hyperosmotic stress treatment 894:935 Global and targeted metabonomic analyses as well as proteomic analysis were performed on IOBA-NHC cells incubated in serum-free media at 280 (control), 380, and 480 mOsm for 24 h. Twenty-one metabolites and seventy-six iTRAQ-identified proteins showed significant changes under at least one hyperosmotic stress treatment as compared with controls. 26260330 4 58 theme proteins 606:613 arg1 changes 579:585 hyperosmotic stress-induced changes 551:585 hyperosmotic stress-induced changes of metabolites and proteins 551:613 This study employed a spontaneously immortalized normal human conjunctival cell line, IOBA-NHC, as a model to investigate hyperosmotic stress-induced changes of metabolites and proteins. 26260330 3 59 theme Recent 286:291 arg1 efforts 302:308 Recent research efforts 286:308 Recent research efforts on dry eye 286:319 Recent research efforts on dry eye have been directed toward biomarker discovery for diagnosis, response to treatment, and disease mechanisms. 26260330 7 60 link O-linked 1205:1212 arg1 synthesis 1191:1199 glycerophosphocholine synthesis 1169:1199 glycerophosphocholine synthesis 1169:1199 This study is the first to identify glycerophosphocholine synthesis and O-linked β-N-acetylglucosamine glycosylation as key activated pathways in ocular surface cells under hyperosmotic stress. 26260330 7 60 link O-linked 1205:1212 arg1 pathways 1267:1274 key activated pathways 1253:1274 key activated pathways in ocular surface cells under hyperosmotic stress 1253:1324 This study is the first to identify glycerophosphocholine synthesis and O-linked β-N-acetylglucosamine glycosylation as key activated pathways in ocular surface cells under hyperosmotic stress. 26260330 7 60 link O-linked 1205:1212 arg1 glycosylation 1236:1248 O-linked β-N-acetylglucosamine glycosylation 1205:1248 O-linked β-N-acetylglucosamine glycosylation 1205:1248 This study is the first to identify glycerophosphocholine synthesis and O-linked β-N-acetylglucosamine glycosylation as key activated pathways in ocular surface cells under hyperosmotic stress. 26260330 6 61 theme pathways 1045:1052 arg1 involvement 1017:1027 the involvement 1013:1027 the involvement of inflammatory pathways such as prostaglandin 2 synthesis in IOBA-NHC cells 1013:1104 SWATH-based proteomic analysis further confirmed the involvement of inflammatory pathways such as prostaglandin 2 synthesis in IOBA-NHC cells under hyperosmotic stress. 26260330 0 62 theme Cells 75:79 arg1 Analysis 33:40 Global Metabonomic and Proteomic Analysis 0:40 Global Metabonomic and Proteomic Analysis of Human Conjunctival Epithelial Cells (IOBA-NHC) in Response to Hyperosmotic Stress. 0:126 Global Metabonomic and Proteomic Analysis of Human Conjunctival Epithelial Cells (IOBA-NHC) in Response to Hyperosmotic Stress. 26260330 1 63 theme Dry 129:131 arg1 disease 171:177 a multifactorial inflammatory disease 141:177 a multifactorial inflammatory disease affecting the ocular surface 141:206 "Dry eye" is a multifactorial inflammatory disease affecting the ocular surface. 26260330 1 63 theme Dry 129:131 arg1 " 136:136 "Dry eye" 128:136 "Dry eye" 128:136 "Dry eye" is a multifactorial inflammatory disease affecting the ocular surface. 26260330 8 64 theme metabolite 1374:1383 arg1 markers 1385:1391 metabolite markers 1374:1391 metabolite markers of dry eye 1374:1402 These findings extend the current knowledge in metabolite markers of dry eye and provide potential therapeutic targets for its treatment. 26260330 6 65 theme inflammatory 1032:1043 arg1 synthesis 1078:1086 prostaglandin 2 synthesis 1062:1086 prostaglandin 2 synthesis 1062:1086 SWATH-based proteomic analysis further confirmed the involvement of inflammatory pathways such as prostaglandin 2 synthesis in IOBA-NHC cells under hyperosmotic stress. 26260330 6 65 theme inflammatory 1032:1043 arg1 pathways 1045:1052 inflammatory pathways 1032:1052 inflammatory pathways such as prostaglandin 2 synthesis 1032:1086 SWATH-based proteomic analysis further confirmed the involvement of inflammatory pathways such as prostaglandin 2 synthesis in IOBA-NHC cells under hyperosmotic stress. 26260330 0 66 theme Epithelial 64:73 arg1 IOBA-NHC 82:89 IOBA-NHC 82:89 IOBA-NHC 82:89 Global Metabonomic and Proteomic Analysis of Human Conjunctival Epithelial Cells (IOBA-NHC) in Response to Hyperosmotic Stress. 26260330 0 66 theme Epithelial 64:73 arg1 Cells 75:79 Human Conjunctival Epithelial Cells 45:79 Human Conjunctival Epithelial Cells (IOBA-NHC) 45:90 Global Metabonomic and Proteomic Analysis of Human Conjunctival Epithelial Cells (IOBA-NHC) in Response to Hyperosmotic Stress. 26260330 4 67 theme cell 504:507 arg1 IOBA-NHC 515:522 IOBA-NHC 515:522 IOBA-NHC 515:522 This study employed a spontaneously immortalized normal human conjunctival cell line, IOBA-NHC, as a model to investigate hyperosmotic stress-induced changes of metabolites and proteins. 26260330 4 67 theme cell 504:507 arg1 line 509:512 normal human conjunctival cell line 478:512 normal human conjunctival cell line 478:512 This study employed a spontaneously immortalized normal human conjunctival cell line, IOBA-NHC, as a model to investigate hyperosmotic stress-induced changes of metabolites and proteins. 26260330 4 67 theme cell 504:507 arg1 model 530:534 a model 528:534 a model to investigate hyperosmotic stress-induced changes of metabolites and proteins 528:613 This study employed a spontaneously immortalized normal human conjunctival cell line, IOBA-NHC, as a model to investigate hyperosmotic stress-induced changes of metabolites and proteins. 26260330 2 68 theme dry 233:235 arg1 eye 237:239 dry eye 233:239 dry eye 233:239 Tear hyperosmolarity in dry eye contributes to inflammation and cell damage. 26260330 1 69 theme eye 133:135 arg1 disease 171:177 a multifactorial inflammatory disease 141:177 a multifactorial inflammatory disease affecting the ocular surface 141:206 "Dry eye" is a multifactorial inflammatory disease affecting the ocular surface. 26260330 1 69 theme eye 133:135 arg1 " 136:136 "Dry eye" 128:136 "Dry eye" 128:136 "Dry eye" is a multifactorial inflammatory disease affecting the ocular surface. 26260330 3 70 from efforts 302:308 arg1 eye 317:319 dry eye 313:319 dry eye 313:319 Recent research efforts on dry eye have been directed toward biomarker discovery for diagnosis, response to treatment, and disease mechanisms. 26091356 5 0 with ELISA 1010:1014 arg1 WFA 1021:1023 WFA 1021:1023 WFA 1021:1023 The CC-related glycosylation change was verified by the lectin-antibody sandwich ELISA with WFA in two cohorts: (1) 78 Opisthorchis viverrini infected patients without CC and 78 with CC, (2) 33 CC patients and 40 hepatolithiasis patients (the same cohort used for the above lectin microarray). 26091356 4 1 theme statistical 703:713 arg1 analysis 715:722 the statistical analysis 699:722 the statistical analysis 699:722 The high-throughput analysis detected disease-specific alterations of glycosylation, and the statistical analysis confirmed that use of Wisteria floribunda agglutinin (WFA) alone produced a diagnostic score sufficient for discriminating 33 CC cases from 40 hepatolithiasis patients and 48 normal controls (p < 0.0001). 26091356 7 2 theme Sensitive 1373:1381 arg1 detection 1383:1391 Sensitive detection 1373:1391 Sensitive detection of qualitative alterations of sialylated MUC1 glycosylation 1373:1451 Sensitive detection of qualitative alterations of sialylated MUC1 glycosylation is indispensable for the development of our glycodiagnostic test for CC. 26091356 6 3 theme = 1314:1314 arg1 ratio 1308:1312 odds ratio 1303:1312 odds ratio = 1.047 1303:1320 The WFA positivity distinguished patients with CC (opisthorchiasis: p < 0.0001, odds ratio = 1.047; hepatolithiasis: p = 0.0002, odds ratio = 1.018). 26091356 5 4 theme Opisthorchis 1048:1059 arg1 viverrini 1061:1069 78 Opisthorchis viverrini 1045:1069 78 Opisthorchis viverrini 1045:1069 The CC-related glycosylation change was verified by the lectin-antibody sandwich ELISA with WFA in two cohorts: (1) 78 Opisthorchis viverrini infected patients without CC and 78 with CC, (2) 33 CC patients and 40 hepatolithiasis patients (the same cohort used for the above lectin microarray). 26091356 1 5 theme MUC1 253:256 arg1 glycosylation 258:270 the MUC1 glycosylation 249:270 the MUC1 glycosylation 249:270 Glycoform of mucin 1 (MUC1) in cancerous cells changes markedly with cell differentiation, and thus, qualitative detection and verification of the MUC1 glycosylation changes have potential diagnostic value. 26091356 6 6 theme WFA 1227:1229 arg1 positivity 1231:1240 The WFA positivity 1223:1240 The WFA positivity 1223:1240 The WFA positivity distinguished patients with CC (opisthorchiasis: p < 0.0001, odds ratio = 1.047; hepatolithiasis: p = 0.0002, odds ratio = 1.018). 26091356 1 7 theme glycosylation 258:270 arg1 verification 233:244 verification 233:244 verification 233:244 Glycoform of mucin 1 (MUC1) in cancerous cells changes markedly with cell differentiation, and thus, qualitative detection and verification of the MUC1 glycosylation changes have potential diagnostic value. 26091356 1 7 theme glycosylation 258:270 arg1 detection 219:227 detection 219:227 detection 219:227 Glycoform of mucin 1 (MUC1) in cancerous cells changes markedly with cell differentiation, and thus, qualitative detection and verification of the MUC1 glycosylation changes have potential diagnostic value. 26091356 4 8 theme agglutinin 766:775 arg1 use 739:741 use 739:741 use of Wisteria floribunda agglutinin (WFA) 739:781 The high-throughput analysis detected disease-specific alterations of glycosylation, and the statistical analysis confirmed that use of Wisteria floribunda agglutinin (WFA) alone produced a diagnostic score sufficient for discriminating 33 CC cases from 40 hepatolithiasis patients and 48 normal controls (p < 0.0001). 26091356 4 9 from patients 883:890 arg1 controls 906:913 48 normal controls 896:913 48 normal controls (p < 0.0001) 896:926 The high-throughput analysis detected disease-specific alterations of glycosylation, and the statistical analysis confirmed that use of Wisteria floribunda agglutinin (WFA) alone produced a diagnostic score sufficient for discriminating 33 CC cases from 40 hepatolithiasis patients and 48 normal controls (p < 0.0001). 26091356 4 9 from patients 883:890 arg1 p 916:916 p < 0.0001 916:925 p < 0.0001 916:925 The high-throughput analysis detected disease-specific alterations of glycosylation, and the statistical analysis confirmed that use of Wisteria floribunda agglutinin (WFA) alone produced a diagnostic score sufficient for discriminating 33 CC cases from 40 hepatolithiasis patients and 48 normal controls (p < 0.0001). 26091356 4 9 from patients 883:890 arg1 cases 853:857 33 CC cases 847:857 33 CC cases from 40 hepatolithiasis patients 847:890 The high-throughput analysis detected disease-specific alterations of glycosylation, and the statistical analysis confirmed that use of Wisteria floribunda agglutinin (WFA) alone produced a diagnostic score sufficient for discriminating 33 CC cases from 40 hepatolithiasis patients and 48 normal controls (p < 0.0001). 26091356 4 10 theme normal 899:904 arg1 p 916:916 p < 0.0001 916:925 p < 0.0001 916:925 The high-throughput analysis detected disease-specific alterations of glycosylation, and the statistical analysis confirmed that use of Wisteria floribunda agglutinin (WFA) alone produced a diagnostic score sufficient for discriminating 33 CC cases from 40 hepatolithiasis patients and 48 normal controls (p < 0.0001). 26091356 4 10 theme normal 899:904 arg1 controls 906:913 48 normal controls 896:913 48 normal controls (p < 0.0001) 896:926 The high-throughput analysis detected disease-specific alterations of glycosylation, and the statistical analysis confirmed that use of Wisteria floribunda agglutinin (WFA) alone produced a diagnostic score sufficient for discriminating 33 CC cases from 40 hepatolithiasis patients and 48 normal controls (p < 0.0001). 26091356 3 11 theme glycan 558:563 arg1 profiles 565:572 the glycan profiles 554:572 the glycan profiles of sialylated MUC1 in 5 μL of sera 554:607 The focused glycan analysis using 43-lectin-immobilized microarray could obtain the glycan profiles of sialylated MUC1 in 5 μL of sera. 26091356 7 12 theme glycodiagnostic 1497:1511 arg1 test 1513:1516 our glycodiagnostic test 1493:1516 our glycodiagnostic test for CC 1493:1523 Sensitive detection of qualitative alterations of sialylated MUC1 glycosylation is indispensable for the development of our glycodiagnostic test for CC. 26091356 7 13 theme sialylated 1423:1432 arg1 glycosylation 1439:1451 sialylated MUC1 glycosylation 1423:1451 sialylated MUC1 glycosylation 1423:1451 Sensitive detection of qualitative alterations of sialylated MUC1 glycosylation is indispensable for the development of our glycodiagnostic test for CC. 26091356 6 14 dep distinguished 1242:1254 arg1 opisthorchiasis 1274:1288 opisthorchiasis 1274:1288 opisthorchiasis 1274:1288 The WFA positivity distinguished patients with CC (opisthorchiasis: p < 0.0001, odds ratio = 1.047; hepatolithiasis: p = 0.0002, odds ratio = 1.018). 26091356 4 15 theme floribunda 755:764 arg1 WFA 778:780 WFA 778:780 WFA 778:780 The high-throughput analysis detected disease-specific alterations of glycosylation, and the statistical analysis confirmed that use of Wisteria floribunda agglutinin (WFA) alone produced a diagnostic score sufficient for discriminating 33 CC cases from 40 hepatolithiasis patients and 48 normal controls (p < 0.0001). 26091356 4 15 theme floribunda 755:764 arg1 agglutinin 766:775 Wisteria floribunda agglutinin 746:775 Wisteria floribunda agglutinin (WFA) 746:781 The high-throughput analysis detected disease-specific alterations of glycosylation, and the statistical analysis confirmed that use of Wisteria floribunda agglutinin (WFA) alone produced a diagnostic score sufficient for discriminating 33 CC cases from 40 hepatolithiasis patients and 48 normal controls (p < 0.0001). 26091356 5 16 theme lectin-antibody 985:999 arg1 ELISA 1010:1014 the lectin-antibody sandwich ELISA 981:1014 the lectin-antibody sandwich ELISA with WFA in two cohorts 981:1038 The CC-related glycosylation change was verified by the lectin-antibody sandwich ELISA with WFA in two cohorts: (1) 78 Opisthorchis viverrini infected patients without CC and 78 with CC, (2) 33 CC patients and 40 hepatolithiasis patients (the same cohort used for the above lectin microarray). 26091356 7 17 gly sialylated 1423:1432 arg1 glycosylation 1439:1451 sialylated MUC1 glycosylation 1423:1451 sialylated MUC1 glycosylation 1423:1451 Sensitive detection of qualitative alterations of sialylated MUC1 glycosylation is indispensable for the development of our glycodiagnostic test for CC. 26091356 4 18 theme glycosylation 680:692 arg1 alterations 665:675 disease-specific alterations 648:675 disease-specific alterations of glycosylation 648:692 The high-throughput analysis detected disease-specific alterations of glycosylation, and the statistical analysis confirmed that use of Wisteria floribunda agglutinin (WFA) alone produced a diagnostic score sufficient for discriminating 33 CC cases from 40 hepatolithiasis patients and 48 normal controls (p < 0.0001). 26091356 6 19 dep = 1314:1314 arg1 1.047 1316:1320 1.047 1316:1320 1.047 1316:1320 The WFA positivity distinguished patients with CC (opisthorchiasis: p < 0.0001, odds ratio = 1.047; hepatolithiasis: p = 0.0002, odds ratio = 1.018). 26091356 6 20 dep opisthorchiasis 1274:1288 arg1 odds 1352:1355 odds ratio = 1.018 1352:1369 odds ratio = 1.018 1352:1369 The WFA positivity distinguished patients with CC (opisthorchiasis: p < 0.0001, odds ratio = 1.047; hepatolithiasis: p = 0.0002, odds ratio = 1.018). 26091356 6 20 dep opisthorchiasis 1274:1288 arg1 ratio 1308:1312 odds ratio 1303:1312 odds ratio = 1.047 1303:1320 The WFA positivity distinguished patients with CC (opisthorchiasis: p < 0.0001, odds ratio = 1.047; hepatolithiasis: p = 0.0002, odds ratio = 1.018). 26091356 6 20 dep opisthorchiasis 1274:1288 arg1 p 1291:1291 p < 0.0001 1291:1300 p < 0.0001 1291:1300 The WFA positivity distinguished patients with CC (opisthorchiasis: p < 0.0001, odds ratio = 1.047; hepatolithiasis: p = 0.0002, odds ratio = 1.018). 26091356 6 20 dep opisthorchiasis 1274:1288 arg1 0.0002 1344:1349 hepatolithiasis: p = 0.0002 1323:1349 hepatolithiasis: p = 0.0002 1323:1349 The WFA positivity distinguished patients with CC (opisthorchiasis: p < 0.0001, odds ratio = 1.047; hepatolithiasis: p = 0.0002, odds ratio = 1.018). 26091356 5 21 theme sandwich 1001:1008 arg1 ELISA 1010:1014 the lectin-antibody sandwich ELISA 981:1014 the lectin-antibody sandwich ELISA with WFA in two cohorts 981:1038 The CC-related glycosylation change was verified by the lectin-antibody sandwich ELISA with WFA in two cohorts: (1) 78 Opisthorchis viverrini infected patients without CC and 78 with CC, (2) 33 CC patients and 40 hepatolithiasis patients (the same cohort used for the above lectin microarray). 26091356 5 22 from ELISA 1010:1014 arg1 cohorts 1032:1038 two cohorts 1028:1038 two cohorts 1028:1038 The CC-related glycosylation change was verified by the lectin-antibody sandwich ELISA with WFA in two cohorts: (1) 78 Opisthorchis viverrini infected patients without CC and 78 with CC, (2) 33 CC patients and 40 hepatolithiasis patients (the same cohort used for the above lectin microarray). 26091356 1 23 theme cell 175:178 arg1 differentiation 180:194 cell differentiation 175:194 cell differentiation 175:194 Glycoform of mucin 1 (MUC1) in cancerous cells changes markedly with cell differentiation, and thus, qualitative detection and verification of the MUC1 glycosylation changes have potential diagnostic value. 26091356 0 24 theme Microarray-Based 7:22 arg1 Verification 39:50 Lectin Microarray-Based Sero-Biomarker Verification 0:50 Lectin Microarray-Based Sero-Biomarker Verification 0:50 Lectin Microarray-Based Sero-Biomarker Verification Targeting Aberrant O-Linked Glycosylation on Mucin 1. 26091356 5 25 theme hepatolithiasis 1142:1156 arg1 patients 1080:1087 patients 1080:1087 patients without CC 1080:1098 The CC-related glycosylation change was verified by the lectin-antibody sandwich ELISA with WFA in two cohorts: (1) 78 Opisthorchis viverrini infected patients without CC and 78 with CC, (2) 33 CC patients and 40 hepatolithiasis patients (the same cohort used for the above lectin microarray). 26091356 5 25 theme hepatolithiasis 1142:1156 arg1 patients 1158:1165 40 hepatolithiasis patients 1139:1165 40 hepatolithiasis patients 1139:1165 The CC-related glycosylation change was verified by the lectin-antibody sandwich ELISA with WFA in two cohorts: (1) 78 Opisthorchis viverrini infected patients without CC and 78 with CC, (2) 33 CC patients and 40 hepatolithiasis patients (the same cohort used for the above lectin microarray). 26091356 3 26 theme sialylated 577:586 arg1 MUC1 588:591 sialylated MUC1 577:591 sialylated MUC1 in 5 μL of sera 577:607 The focused glycan analysis using 43-lectin-immobilized microarray could obtain the glycan profiles of sialylated MUC1 in 5 μL of sera. 26091356 5 27 dep infected 1071:1078 arg1 1 1042:1042 1 1042:1042 1 1042:1042 The CC-related glycosylation change was verified by the lectin-antibody sandwich ELISA with WFA in two cohorts: (1) 78 Opisthorchis viverrini infected patients without CC and 78 with CC, (2) 33 CC patients and 40 hepatolithiasis patients (the same cohort used for the above lectin microarray). 26091356 0 28 theme Lectin 0:5 arg1 Verification 39:50 Lectin Microarray-Based Sero-Biomarker Verification 0:50 Lectin Microarray-Based Sero-Biomarker Verification 0:50 Lectin Microarray-Based Sero-Biomarker Verification Targeting Aberrant O-Linked Glycosylation on Mucin 1. 26091356 4 29 theme hepatolithiasis 867:881 arg1 patients 883:890 40 hepatolithiasis patients 864:890 40 hepatolithiasis patients 864:890 The high-throughput analysis detected disease-specific alterations of glycosylation, and the statistical analysis confirmed that use of Wisteria floribunda agglutinin (WFA) alone produced a diagnostic score sufficient for discriminating 33 CC cases from 40 hepatolithiasis patients and 48 normal controls (p < 0.0001). 26091356 7 30 theme alterations 1408:1418 arg1 detection 1383:1391 Sensitive detection 1373:1391 Sensitive detection of qualitative alterations of sialylated MUC1 glycosylation 1373:1451 Sensitive detection of qualitative alterations of sialylated MUC1 glycosylation is indispensable for the development of our glycodiagnostic test for CC. 26091356 3 31 theme MUC1 588:591 arg1 profiles 565:572 the glycan profiles 554:572 the glycan profiles of sialylated MUC1 in 5 μL of sera 554:607 The focused glycan analysis using 43-lectin-immobilized microarray could obtain the glycan profiles of sialylated MUC1 in 5 μL of sera. 26091356 5 32 with patients 1080:1087 arg1 CC 1112:1113 CC 1112:1113 CC 1112:1113 The CC-related glycosylation change was verified by the lectin-antibody sandwich ELISA with WFA in two cohorts: (1) 78 Opisthorchis viverrini infected patients without CC and 78 with CC, (2) 33 CC patients and 40 hepatolithiasis patients (the same cohort used for the above lectin microarray). 26091356 6 33 theme odds 1303:1306 arg1 ratio 1308:1312 odds ratio 1303:1312 odds ratio = 1.047 1303:1320 The WFA positivity distinguished patients with CC (opisthorchiasis: p < 0.0001, odds ratio = 1.047; hepatolithiasis: p = 0.0002, odds ratio = 1.018). 26091356 1 34 theme potential 285:293 arg1 value 306:310 potential diagnostic value 285:310 potential diagnostic value 285:310 Glycoform of mucin 1 (MUC1) in cancerous cells changes markedly with cell differentiation, and thus, qualitative detection and verification of the MUC1 glycosylation changes have potential diagnostic value. 26091356 6 35 theme < 1293:1293 arg1 p 1291:1291 p < 0.0001 1291:1300 p < 0.0001 1291:1300 The WFA positivity distinguished patients with CC (opisthorchiasis: p < 0.0001, odds ratio = 1.047; hepatolithiasis: p = 0.0002, odds ratio = 1.018). 26091356 2 36 from changes 370:376 arg1 CC 401:402 CC 401:402 CC 401:402 We have developed an ultrasensitive method to detect the changes in cholangiocarcinoma (CC), which produces MUC1, and applied it in the diagnostics development. 26091356 2 36 from changes 370:376 arg1 cholangiocarcinoma 381:398 cholangiocarcinoma 381:398 cholangiocarcinoma (CC) 381:403 We have developed an ultrasensitive method to detect the changes in cholangiocarcinoma (CC), which produces MUC1, and applied it in the diagnostics development. 26091356 1 37 theme mucin 119:123 arg1 MUC1 128:131 mucin 1 (MUC1) 119:132 mucin 1 (MUC1) 119:132 Glycoform of mucin 1 (MUC1) in cancerous cells changes markedly with cell differentiation, and thus, qualitative detection and verification of the MUC1 glycosylation changes have potential diagnostic value. 26091356 6 38 with patients 1256:1263 arg1 CC 1270:1271 CC 1270:1271 CC 1270:1271 The WFA positivity distinguished patients with CC (opisthorchiasis: p < 0.0001, odds ratio = 1.047; hepatolithiasis: p = 0.0002, odds ratio = 1.018). 26091356 0 39 theme Sero-Biomarker 24:37 arg1 Verification 39:50 Lectin Microarray-Based Sero-Biomarker Verification 0:50 Lectin Microarray-Based Sero-Biomarker Verification 0:50 Lectin Microarray-Based Sero-Biomarker Verification Targeting Aberrant O-Linked Glycosylation on Mucin 1. 26091356 1 40 theme diagnostic 295:304 arg1 value 306:310 potential diagnostic value 285:310 potential diagnostic value 285:310 Glycoform of mucin 1 (MUC1) in cancerous cells changes markedly with cell differentiation, and thus, qualitative detection and verification of the MUC1 glycosylation changes have potential diagnostic value. 26091356 3 41 theme glycan 486:491 arg1 analysis 493:500 The focused glycan analysis 474:500 The focused glycan analysis using 43-lectin-immobilized microarray 474:539 The focused glycan analysis using 43-lectin-immobilized microarray could obtain the glycan profiles of sialylated MUC1 in 5 μL of sera. 26091356 3 42 from μL 598:599 arg1 profiles 565:572 the glycan profiles 554:572 the glycan profiles of sialylated MUC1 in 5 μL of sera 554:607 The focused glycan analysis using 43-lectin-immobilized microarray could obtain the glycan profiles of sialylated MUC1 in 5 μL of sera. 26091356 3 43 theme 43-lectin-immobilized 508:528 arg1 microarray 530:539 43-lectin-immobilized microarray 508:539 43-lectin-immobilized microarray 508:539 The focused glycan analysis using 43-lectin-immobilized microarray could obtain the glycan profiles of sialylated MUC1 in 5 μL of sera. 26091356 0 44 theme Aberrant 62:69 arg1 Glycosylation 80:92 Aberrant O-Linked Glycosylation 62:92 Aberrant O-Linked Glycosylation 62:92 Lectin Microarray-Based Sero-Biomarker Verification Targeting Aberrant O-Linked Glycosylation on Mucin 1. 26091356 3 45 gly sialylated 577:586 arg1 MUC1 588:591 sialylated MUC1 577:591 sialylated MUC1 in 5 μL of sera 577:607 The focused glycan analysis using 43-lectin-immobilized microarray could obtain the glycan profiles of sialylated MUC1 in 5 μL of sera. 26091356 2 46 theme diagnostics 449:459 arg1 development 461:471 the diagnostics development 445:471 the diagnostics development 445:471 We have developed an ultrasensitive method to detect the changes in cholangiocarcinoma (CC), which produces MUC1, and applied it in the diagnostics development. 26091356 6 47 theme = 1342:1342 arg1 0.0002 1344:1349 hepatolithiasis: p = 0.0002 1323:1349 hepatolithiasis: p = 0.0002 1323:1349 The WFA positivity distinguished patients with CC (opisthorchiasis: p < 0.0001, odds ratio = 1.047; hepatolithiasis: p = 0.0002, odds ratio = 1.018). 26091356 7 48 theme test 1513:1516 arg1 development 1478:1488 the development 1474:1488 the development of our glycodiagnostic test for CC 1474:1523 Sensitive detection of qualitative alterations of sialylated MUC1 glycosylation is indispensable for the development of our glycodiagnostic test for CC. 26091356 1 49 theme qualitative 207:217 arg1 detection 219:227 detection 219:227 detection 219:227 Glycoform of mucin 1 (MUC1) in cancerous cells changes markedly with cell differentiation, and thus, qualitative detection and verification of the MUC1 glycosylation changes have potential diagnostic value. 26091356 6 50 theme p 1340:1340 arg1 0.0002 1344:1349 hepatolithiasis: p = 0.0002 1323:1349 hepatolithiasis: p = 0.0002 1323:1349 The WFA positivity distinguished patients with CC (opisthorchiasis: p < 0.0001, odds ratio = 1.047; hepatolithiasis: p = 0.0002, odds ratio = 1.018). 26091356 6 51 dep odds 1352:1355 arg1 ratio 1357:1361 ratio 1357:1361 odds ratio = 1.018 1352:1369 The WFA positivity distinguished patients with CC (opisthorchiasis: p < 0.0001, odds ratio = 1.047; hepatolithiasis: p = 0.0002, odds ratio = 1.018). 26091356 6 52 dep = 1363:1363 arg1 1.018 1365:1369 1.018 1365:1369 1.018 1365:1369 The WFA positivity distinguished patients with CC (opisthorchiasis: p < 0.0001, odds ratio = 1.047; hepatolithiasis: p = 0.0002, odds ratio = 1.018). 26091356 3 53 theme focused 478:484 arg1 analysis 493:500 The focused glycan analysis 474:500 The focused glycan analysis using 43-lectin-immobilized microarray 474:539 The focused glycan analysis using 43-lectin-immobilized microarray could obtain the glycan profiles of sialylated MUC1 in 5 μL of sera. 26091356 0 54 theme O-Linked 71:78 arg1 Glycosylation 80:92 Aberrant O-Linked Glycosylation 62:92 Aberrant O-Linked Glycosylation 62:92 Lectin Microarray-Based Sero-Biomarker Verification Targeting Aberrant O-Linked Glycosylation on Mucin 1. 26091356 5 55 theme CC 1123:1124 arg1 patients 1126:1133 33 CC patients 1120:1133 33 CC patients 1120:1133 The CC-related glycosylation change was verified by the lectin-antibody sandwich ELISA with WFA in two cohorts: (1) 78 Opisthorchis viverrini infected patients without CC and 78 with CC, (2) 33 CC patients and 40 hepatolithiasis patients (the same cohort used for the above lectin microarray). 26091356 5 55 theme CC 1123:1124 arg1 patients 1080:1087 patients 1080:1087 patients without CC 1080:1098 The CC-related glycosylation change was verified by the lectin-antibody sandwich ELISA with WFA in two cohorts: (1) 78 Opisthorchis viverrini infected patients without CC and 78 with CC, (2) 33 CC patients and 40 hepatolithiasis patients (the same cohort used for the above lectin microarray). 26091356 7 56 theme MUC1 1434:1437 arg1 glycosylation 1439:1451 sialylated MUC1 glycosylation 1423:1451 sialylated MUC1 glycosylation 1423:1451 Sensitive detection of qualitative alterations of sialylated MUC1 glycosylation is indispensable for the development of our glycodiagnostic test for CC. 26091356 4 57 theme CC 850:851 arg1 cases 853:857 33 CC cases 847:857 33 CC cases from 40 hepatolithiasis patients 847:890 The high-throughput analysis detected disease-specific alterations of glycosylation, and the statistical analysis confirmed that use of Wisteria floribunda agglutinin (WFA) alone produced a diagnostic score sufficient for discriminating 33 CC cases from 40 hepatolithiasis patients and 48 normal controls (p < 0.0001). 26091356 1 58 theme MUC1 128:131 arg1 Glycoform 106:114 Glycoform 106:114 Glycoform of mucin 1 (MUC1) in cancerous cells 106:151 Glycoform of mucin 1 (MUC1) in cancerous cells changes markedly with cell differentiation, and thus, qualitative detection and verification of the MUC1 glycosylation changes have potential diagnostic value. 26091356 3 59 from profiles 565:572 arg1 μL 598:599 5 μL 596:599 5 μL of sera 596:607 The focused glycan analysis using 43-lectin-immobilized microarray could obtain the glycan profiles of sialylated MUC1 in 5 μL of sera. 26091356 5 60 theme glycosylation 944:956 arg1 change 958:963 The CC-related glycosylation change 929:963 The CC-related glycosylation change 929:963 The CC-related glycosylation change was verified by the lectin-antibody sandwich ELISA with WFA in two cohorts: (1) 78 Opisthorchis viverrini infected patients without CC and 78 with CC, (2) 33 CC patients and 40 hepatolithiasis patients (the same cohort used for the above lectin microarray). 26091356 7 61 theme glycosylation 1439:1451 arg1 alterations 1408:1418 qualitative alterations 1396:1418 qualitative alterations of sialylated MUC1 glycosylation 1396:1451 Sensitive detection of qualitative alterations of sialylated MUC1 glycosylation is indispensable for the development of our glycodiagnostic test for CC. 26091356 2 62 theme ultrasensitive 334:347 arg1 method 349:354 an ultrasensitive method 331:354 an ultrasensitive method to detect the changes in cholangiocarcinoma (CC), which produces MUC1 331:424 We have developed an ultrasensitive method to detect the changes in cholangiocarcinoma (CC), which produces MUC1, and applied it in the diagnostics development. 26091356 5 63 dep patients 1126:1133 arg1 cohort 1177:1182 the same cohort 1168:1182 the same cohort used for the above lectin microarray 1168:1219 The CC-related glycosylation change was verified by the lectin-antibody sandwich ELISA with WFA in two cohorts: (1) 78 Opisthorchis viverrini infected patients without CC and 78 with CC, (2) 33 CC patients and 40 hepatolithiasis patients (the same cohort used for the above lectin microarray). 26091356 5 63 dep patients 1126:1133 arg1 2 1117:1117 2 1117:1117 2 1117:1117 The CC-related glycosylation change was verified by the lectin-antibody sandwich ELISA with WFA in two cohorts: (1) 78 Opisthorchis viverrini infected patients without CC and 78 with CC, (2) 33 CC patients and 40 hepatolithiasis patients (the same cohort used for the above lectin microarray). 26091356 4 64 theme < 918:918 arg1 p 916:916 p < 0.0001 916:925 p < 0.0001 916:925 The high-throughput analysis detected disease-specific alterations of glycosylation, and the statistical analysis confirmed that use of Wisteria floribunda agglutinin (WFA) alone produced a diagnostic score sufficient for discriminating 33 CC cases from 40 hepatolithiasis patients and 48 normal controls (p < 0.0001). 26091356 4 64 theme < 918:918 arg1 controls 906:913 48 normal controls 896:913 48 normal controls (p < 0.0001) 896:926 The high-throughput analysis detected disease-specific alterations of glycosylation, and the statistical analysis confirmed that use of Wisteria floribunda agglutinin (WFA) alone produced a diagnostic score sufficient for discriminating 33 CC cases from 40 hepatolithiasis patients and 48 normal controls (p < 0.0001). 26091356 4 65 theme diagnostic 800:809 arg1 score 811:815 a diagnostic score 798:815 a diagnostic score sufficient for discriminating 33 CC cases from 40 hepatolithiasis patients and 48 normal controls (p < 0.0001) 798:926 The high-throughput analysis detected disease-specific alterations of glycosylation, and the statistical analysis confirmed that use of Wisteria floribunda agglutinin (WFA) alone produced a diagnostic score sufficient for discriminating 33 CC cases from 40 hepatolithiasis patients and 48 normal controls (p < 0.0001). 26091356 5 66 theme CC-related 933:942 arg1 change 958:963 The CC-related glycosylation change 929:963 The CC-related glycosylation change 929:963 The CC-related glycosylation change was verified by the lectin-antibody sandwich ELISA with WFA in two cohorts: (1) 78 Opisthorchis viverrini infected patients without CC and 78 with CC, (2) 33 CC patients and 40 hepatolithiasis patients (the same cohort used for the above lectin microarray). 26091356 1 67 from Glycoform 106:114 arg1 cells 147:151 cancerous cells 137:151 cancerous cells 137:151 Glycoform of mucin 1 (MUC1) in cancerous cells changes markedly with cell differentiation, and thus, qualitative detection and verification of the MUC1 glycosylation changes have potential diagnostic value. 26091356 4 68 theme Wisteria 746:753 arg1 WFA 778:780 WFA 778:780 WFA 778:780 The high-throughput analysis detected disease-specific alterations of glycosylation, and the statistical analysis confirmed that use of Wisteria floribunda agglutinin (WFA) alone produced a diagnostic score sufficient for discriminating 33 CC cases from 40 hepatolithiasis patients and 48 normal controls (p < 0.0001). 26091356 4 68 theme Wisteria 746:753 arg1 agglutinin 766:775 Wisteria floribunda agglutinin 746:775 Wisteria floribunda agglutinin (WFA) 746:781 The high-throughput analysis detected disease-specific alterations of glycosylation, and the statistical analysis confirmed that use of Wisteria floribunda agglutinin (WFA) alone produced a diagnostic score sufficient for discriminating 33 CC cases from 40 hepatolithiasis patients and 48 normal controls (p < 0.0001). 26091356 6 69 theme hepatolithiasis 1323:1337 arg1 0.0002 1344:1349 hepatolithiasis: p = 0.0002 1323:1349 hepatolithiasis: p = 0.0002 1323:1349 The WFA positivity distinguished patients with CC (opisthorchiasis: p < 0.0001, odds ratio = 1.047; hepatolithiasis: p = 0.0002, odds ratio = 1.018). 26091356 4 70 theme disease-specific 648:663 arg1 alterations 665:675 disease-specific alterations 648:675 disease-specific alterations of glycosylation 648:692 The high-throughput analysis detected disease-specific alterations of glycosylation, and the statistical analysis confirmed that use of Wisteria floribunda agglutinin (WFA) alone produced a diagnostic score sufficient for discriminating 33 CC cases from 40 hepatolithiasis patients and 48 normal controls (p < 0.0001). 26091356 3 71 theme sera 604:607 arg1 μL 598:599 5 μL 596:599 5 μL of sera 596:607 The focused glycan analysis using 43-lectin-immobilized microarray could obtain the glycan profiles of sialylated MUC1 in 5 μL of sera. 26091356 1 72 theme cancerous 137:145 arg1 cells 147:151 cancerous cells 137:151 cancerous cells 137:151 Glycoform of mucin 1 (MUC1) in cancerous cells changes markedly with cell differentiation, and thus, qualitative detection and verification of the MUC1 glycosylation changes have potential diagnostic value. 26091356 3 73 from MUC1 588:591 arg1 μL 598:599 5 μL 596:599 5 μL of sera 596:607 The focused glycan analysis using 43-lectin-immobilized microarray could obtain the glycan profiles of sialylated MUC1 in 5 μL of sera. 26091356 4 74 theme high-throughput 614:628 arg1 analysis 630:637 The high-throughput analysis 610:637 The high-throughput analysis 610:637 The high-throughput analysis detected disease-specific alterations of glycosylation, and the statistical analysis confirmed that use of Wisteria floribunda agglutinin (WFA) alone produced a diagnostic score sufficient for discriminating 33 CC cases from 40 hepatolithiasis patients and 48 normal controls (p < 0.0001). 26091356 5 75 theme same 1172:1175 arg1 cohort 1177:1182 the same cohort 1168:1182 the same cohort used for the above lectin microarray 1168:1219 The CC-related glycosylation change was verified by the lectin-antibody sandwich ELISA with WFA in two cohorts: (1) 78 Opisthorchis viverrini infected patients without CC and 78 with CC, (2) 33 CC patients and 40 hepatolithiasis patients (the same cohort used for the above lectin microarray). 26091356 7 76 theme qualitative 1396:1406 arg1 alterations 1408:1418 qualitative alterations 1396:1418 qualitative alterations of sialylated MUC1 glycosylation 1396:1451 Sensitive detection of qualitative alterations of sialylated MUC1 glycosylation is indispensable for the development of our glycodiagnostic test for CC. 26091356 4 77 theme sufficient 817:826 arg1 score 811:815 a diagnostic score 798:815 a diagnostic score sufficient for discriminating 33 CC cases from 40 hepatolithiasis patients and 48 normal controls (p < 0.0001) 798:926 The high-throughput analysis detected disease-specific alterations of glycosylation, and the statistical analysis confirmed that use of Wisteria floribunda agglutinin (WFA) alone produced a diagnostic score sufficient for discriminating 33 CC cases from 40 hepatolithiasis patients and 48 normal controls (p < 0.0001). 26091356 6 78 theme = 1363:1363 arg1 ratio 1357:1361 ratio 1357:1361 odds ratio = 1.018 1352:1369 The WFA positivity distinguished patients with CC (opisthorchiasis: p < 0.0001, odds ratio = 1.047; hepatolithiasis: p = 0.0002, odds ratio = 1.018). 26091356 5 79 theme lectin 1203:1208 arg1 microarray 1210:1219 the above lectin microarray 1193:1219 the above lectin microarray 1193:1219 The CC-related glycosylation change was verified by the lectin-antibody sandwich ELISA with WFA in two cohorts: (1) 78 Opisthorchis viverrini infected patients without CC and 78 with CC, (2) 33 CC patients and 40 hepatolithiasis patients (the same cohort used for the above lectin microarray). 26091356 5 80 theme above 1197:1201 arg1 microarray 1210:1219 the above lectin microarray 1193:1219 the above lectin microarray 1193:1219 The CC-related glycosylation change was verified by the lectin-antibody sandwich ELISA with WFA in two cohorts: (1) 78 Opisthorchis viverrini infected patients without CC and 78 with CC, (2) 33 CC patients and 40 hepatolithiasis patients (the same cohort used for the above lectin microarray). 25268609 3 0 theme tyrosine 654:661 arg1 ratios 644:649 relatively low ratios 629:649 relatively low ratios of tyrosine and histidine 629:675 The peptide chain contained relatively high mole ratios of aspartic acid, glutamic acid and glycine (3.3-3.5 relative to arginine) but relatively low ratios of tyrosine and histidine. 25268609 3 1 theme acid 577:580 arg1 ratios 543:548 relatively high mole ratios 522:548 relatively high mole ratios of aspartic acid, glutamic acid and glycine (3.3-3.5 relative to arginine) 522:623 The peptide chain contained relatively high mole ratios of aspartic acid, glutamic acid and glycine (3.3-3.5 relative to arginine) but relatively low ratios of tyrosine and histidine. 25268609 0 2 theme culture 88:94 arg1 broth 96:100 mycelial culture broth 79:100 mycelial culture broth of a medicinal fungus 79:122 Isolation and structure characterization of an antioxidative glycopeptide from mycelial culture broth of a medicinal fungus. 25268609 3 3 theme low 640:642 arg1 ratios 644:649 relatively low ratios 629:649 relatively low ratios of tyrosine and histidine 629:675 The peptide chain contained relatively high mole ratios of aspartic acid, glutamic acid and glycine (3.3-3.5 relative to arginine) but relatively low ratios of tyrosine and histidine. 25268609 1 4 theme Cordyceps 340:348 arg1 Cs-HK1 359:364 a medicinal fungus Cordyceps sinensis Cs-HK1 321:364 a medicinal fungus Cordyceps sinensis Cs-HK1 321:364 A novel glycopeptide (Cs-GP1) with an average molecular weight (Mw) of 6.0 kDa was isolated and purified by column chromatography from the lower Mw fraction of exopolysaccharide (EPS) produced by a medicinal fungus Cordyceps sinensis Cs-HK1. 25268609 5 5 theme significant 959:969 arg1 effect 982:987 significant protective effect 959:987 significant protective effect against H2O2-induced PC12 cell injury 959:1025 Cs-GP1 exhibited remarkable antioxidant capacity with a Trolox equivalent antioxidant capacity of 1183.8 μmol/g and a ferric reducing ability of 611.1 μmol Fe(II)/g, and significant protective effect against H2O2-induced PC12 cell injury at a minimum dose of 10 μg/mL. 25268609 2 6 gly glycopeptide 480:491 arg2 glycopeptide 480:491 an O-linked glycopeptide 468:491 an O-linked glycopeptide 468:491 Its carbohydrate moiety was mainly composed of glucose and mannose at 3.2:1.0 mole ratio, indicating an O-linked glycopeptide. 25268609 6 7 from species 1168:1174 arg1 bioactivity 1104:1114 bioactivity 1104:1114 bioactivity 1104:1114 This is the first report on the structure and bioactivity of an extracellular glycopeptide from the Cordyceps species. 25268609 6 7 from species 1168:1174 arg1 structure 1090:1098 structure 1090:1098 structure 1090:1098 This is the first report on the structure and bioactivity of an extracellular glycopeptide from the Cordyceps species. 25268609 6 7 from species 1168:1174 arg1 glycopeptide 1136:1147 an extracellular glycopeptide 1119:1147 an extracellular glycopeptide from the Cordyceps species 1119:1174 This is the first report on the structure and bioactivity of an extracellular glycopeptide from the Cordyceps species. 25268609 4 8 theme chain 690:694 arg1 sequence 696:703 The peptide chain sequence 678:703 The peptide chain sequence analyzed after trypsin digestion by LC-MS 678:745 The peptide chain sequence analyzed after trypsin digestion by LC-MS was KNGIFQFGEDCAAGSISHELGGFREFREFLKQAGLE. 25268609 4 8 theme chain 690:694 arg1 KNGIFQFGEDCAAGSISHELGGFREFREFLKQAGLE 751:786 KNGIFQFGEDCAAGSISHELGGFREFREFLKQAGLE 751:786 KNGIFQFGEDCAAGSISHELGGFREFREFLKQAGLE 751:786 The peptide chain sequence analyzed after trypsin digestion by LC-MS was KNGIFQFGEDCAAGSISHELGGFREFREFLKQAGLE. 25268609 6 9 theme glycopeptide 1136:1147 arg1 bioactivity 1104:1114 bioactivity 1104:1114 bioactivity 1104:1114 This is the first report on the structure and bioactivity of an extracellular glycopeptide from the Cordyceps species. 25268609 6 9 theme glycopeptide 1136:1147 arg1 structure 1090:1098 structure 1090:1098 structure 1090:1098 This is the first report on the structure and bioactivity of an extracellular glycopeptide from the Cordyceps species. 25268609 3 10 theme histidine 667:675 arg1 ratios 644:649 relatively low ratios 629:649 relatively low ratios of tyrosine and histidine 629:675 The peptide chain contained relatively high mole ratios of aspartic acid, glutamic acid and glycine (3.3-3.5 relative to arginine) but relatively low ratios of tyrosine and histidine. 25268609 1 11 theme column 233:238 arg1 chromatography 240:253 column chromatography 233:253 column chromatography 233:253 A novel glycopeptide (Cs-GP1) with an average molecular weight (Mw) of 6.0 kDa was isolated and purified by column chromatography from the lower Mw fraction of exopolysaccharide (EPS) produced by a medicinal fungus Cordyceps sinensis Cs-HK1. 25268609 0 12 theme fungus 117:122 arg1 broth 96:100 mycelial culture broth 79:100 mycelial culture broth of a medicinal fungus 79:122 Isolation and structure characterization of an antioxidative glycopeptide from mycelial culture broth of a medicinal fungus. 25268609 6 13 dep structure 1090:1098 arg1 the 1086:1088 the 1086:1088 the 1086:1088 This is the first report on the structure and bioactivity of an extracellular glycopeptide from the Cordyceps species. 25268609 5 14 with ability 923:929 arg1 Trolox 845:850 a Trolox 843:850 a Trolox 843:850 Cs-GP1 exhibited remarkable antioxidant capacity with a Trolox equivalent antioxidant capacity of 1183.8 μmol/g and a ferric reducing ability of 611.1 μmol Fe(II)/g, and significant protective effect against H2O2-induced PC12 cell injury at a minimum dose of 10 μg/mL. 25268609 6 15 theme extracellular 1122:1134 arg1 glycopeptide 1136:1147 an extracellular glycopeptide 1119:1147 an extracellular glycopeptide from the Cordyceps species 1119:1174 This is the first report on the structure and bioactivity of an extracellular glycopeptide from the Cordyceps species. 25268609 5 16 theme equivalent 852:861 arg1 capacity 875:882 equivalent antioxidant capacity 852:882 remarkable antioxidant capacity with a Trolox equivalent antioxidant capacity of 1183.8 μmol/g 806:899 Cs-GP1 exhibited remarkable antioxidant capacity with a Trolox equivalent antioxidant capacity of 1183.8 μmol/g and a ferric reducing ability of 611.1 μmol Fe(II)/g, and significant protective effect against H2O2-induced PC12 cell injury at a minimum dose of 10 μg/mL. 25268609 0 17 theme medicinal 107:115 arg1 fungus 117:122 a medicinal fungus 105:122 a medicinal fungus 105:122 Isolation and structure characterization of an antioxidative glycopeptide from mycelial culture broth of a medicinal fungus. 25268609 1 18 theme medicinal 323:331 arg1 Cs-HK1 359:364 a medicinal fungus Cordyceps sinensis Cs-HK1 321:364 a medicinal fungus Cordyceps sinensis Cs-HK1 321:364 A novel glycopeptide (Cs-GP1) with an average molecular weight (Mw) of 6.0 kDa was isolated and purified by column chromatography from the lower Mw fraction of exopolysaccharide (EPS) produced by a medicinal fungus Cordyceps sinensis Cs-HK1. 25268609 1 19 with glycopeptide 133:144 arg1 Mw 189:190 Mw 189:190 Mw 189:190 A novel glycopeptide (Cs-GP1) with an average molecular weight (Mw) of 6.0 kDa was isolated and purified by column chromatography from the lower Mw fraction of exopolysaccharide (EPS) produced by a medicinal fungus Cordyceps sinensis Cs-HK1. 25268609 1 19 with glycopeptide 133:144 arg1 weight 181:186 an average molecular weight 160:186 an average molecular weight (Mw) of 6.0 kDa 160:202 A novel glycopeptide (Cs-GP1) with an average molecular weight (Mw) of 6.0 kDa was isolated and purified by column chromatography from the lower Mw fraction of exopolysaccharide (EPS) produced by a medicinal fungus Cordyceps sinensis Cs-HK1. 25268609 3 20 theme peptide 498:504 arg1 chain 506:510 The peptide chain 494:510 The peptide chain 494:510 The peptide chain contained relatively high mole ratios of aspartic acid, glutamic acid and glycine (3.3-3.5 relative to arginine) but relatively low ratios of tyrosine and histidine. 25268609 1 21 theme average 163:169 arg1 Mw 189:190 Mw 189:190 Mw 189:190 A novel glycopeptide (Cs-GP1) with an average molecular weight (Mw) of 6.0 kDa was isolated and purified by column chromatography from the lower Mw fraction of exopolysaccharide (EPS) produced by a medicinal fungus Cordyceps sinensis Cs-HK1. 25268609 1 21 theme average 163:169 arg1 weight 181:186 an average molecular weight 160:186 an average molecular weight (Mw) of 6.0 kDa 160:202 A novel glycopeptide (Cs-GP1) with an average molecular weight (Mw) of 6.0 kDa was isolated and purified by column chromatography from the lower Mw fraction of exopolysaccharide (EPS) produced by a medicinal fungus Cordyceps sinensis Cs-HK1. 25268609 1 22 theme fungus 333:338 arg1 Cs-HK1 359:364 a medicinal fungus Cordyceps sinensis Cs-HK1 321:364 a medicinal fungus Cordyceps sinensis Cs-HK1 321:364 A novel glycopeptide (Cs-GP1) with an average molecular weight (Mw) of 6.0 kDa was isolated and purified by column chromatography from the lower Mw fraction of exopolysaccharide (EPS) produced by a medicinal fungus Cordyceps sinensis Cs-HK1. 25268609 3 23 theme mole 538:541 arg1 ratios 543:548 relatively high mole ratios 522:548 relatively high mole ratios of aspartic acid, glutamic acid and glycine (3.3-3.5 relative to arginine) 522:623 The peptide chain contained relatively high mole ratios of aspartic acid, glutamic acid and glycine (3.3-3.5 relative to arginine) but relatively low ratios of tyrosine and histidine. 25268609 1 24 theme molecular 171:179 arg1 Mw 189:190 Mw 189:190 Mw 189:190 A novel glycopeptide (Cs-GP1) with an average molecular weight (Mw) of 6.0 kDa was isolated and purified by column chromatography from the lower Mw fraction of exopolysaccharide (EPS) produced by a medicinal fungus Cordyceps sinensis Cs-HK1. 25268609 1 24 theme molecular 171:179 arg1 weight 181:186 an average molecular weight 160:186 an average molecular weight (Mw) of 6.0 kDa 160:202 A novel glycopeptide (Cs-GP1) with an average molecular weight (Mw) of 6.0 kDa was isolated and purified by column chromatography from the lower Mw fraction of exopolysaccharide (EPS) produced by a medicinal fungus Cordyceps sinensis Cs-HK1. 25268609 5 25 with capacity 829:836 arg1 Trolox 845:850 a Trolox 843:850 a Trolox 843:850 Cs-GP1 exhibited remarkable antioxidant capacity with a Trolox equivalent antioxidant capacity of 1183.8 μmol/g and a ferric reducing ability of 611.1 μmol Fe(II)/g, and significant protective effect against H2O2-induced PC12 cell injury at a minimum dose of 10 μg/mL. 25268609 6 26 theme Cordyceps 1158:1166 arg1 species 1168:1174 the Cordyceps species 1154:1174 the Cordyceps species 1154:1174 This is the first report on the structure and bioactivity of an extracellular glycopeptide from the Cordyceps species. 25268609 4 27 theme peptide 682:688 arg1 sequence 696:703 The peptide chain sequence 678:703 The peptide chain sequence analyzed after trypsin digestion by LC-MS 678:745 The peptide chain sequence analyzed after trypsin digestion by LC-MS was KNGIFQFGEDCAAGSISHELGGFREFREFLKQAGLE. 25268609 4 27 theme peptide 682:688 arg1 KNGIFQFGEDCAAGSISHELGGFREFREFLKQAGLE 751:786 KNGIFQFGEDCAAGSISHELGGFREFREFLKQAGLE 751:786 KNGIFQFGEDCAAGSISHELGGFREFREFLKQAGLE 751:786 The peptide chain sequence analyzed after trypsin digestion by LC-MS was KNGIFQFGEDCAAGSISHELGGFREFREFLKQAGLE. 25268609 4 28 theme trypsin 720:726 arg1 digestion 728:736 trypsin digestion 720:736 trypsin digestion 720:736 The peptide chain sequence analyzed after trypsin digestion by LC-MS was KNGIFQFGEDCAAGSISHELGGFREFREFLKQAGLE. 25268609 5 29 theme remarkable 806:815 arg1 capacity 829:836 remarkable antioxidant capacity 806:836 remarkable antioxidant capacity with a Trolox equivalent antioxidant capacity of 1183.8 μmol/g 806:899 Cs-GP1 exhibited remarkable antioxidant capacity with a Trolox equivalent antioxidant capacity of 1183.8 μmol/g and a ferric reducing ability of 611.1 μmol Fe(II)/g, and significant protective effect against H2O2-induced PC12 cell injury at a minimum dose of 10 μg/mL. 25268609 5 30 theme protective 971:980 arg1 effect 982:987 significant protective effect 959:987 significant protective effect against H2O2-induced PC12 cell injury 959:1025 Cs-GP1 exhibited remarkable antioxidant capacity with a Trolox equivalent antioxidant capacity of 1183.8 μmol/g and a ferric reducing ability of 611.1 μmol Fe(II)/g, and significant protective effect against H2O2-induced PC12 cell injury at a minimum dose of 10 μg/mL. 25268609 5 31 theme cell 1015:1018 arg1 injury 1020:1025 H2O2-induced PC12 cell injury 997:1025 H2O2-induced PC12 cell injury 997:1025 Cs-GP1 exhibited remarkable antioxidant capacity with a Trolox equivalent antioxidant capacity of 1183.8 μmol/g and a ferric reducing ability of 611.1 μmol Fe(II)/g, and significant protective effect against H2O2-induced PC12 cell injury at a minimum dose of 10 μg/mL. 25268609 5 32 theme Fe 945:946 arg1 capacity 829:836 remarkable antioxidant capacity 806:836 remarkable antioxidant capacity with a Trolox equivalent antioxidant capacity of 1183.8 μmol/g 806:899 Cs-GP1 exhibited remarkable antioxidant capacity with a Trolox equivalent antioxidant capacity of 1183.8 μmol/g and a ferric reducing ability of 611.1 μmol Fe(II)/g, and significant protective effect against H2O2-induced PC12 cell injury at a minimum dose of 10 μg/mL. 25268609 5 32 theme Fe 945:946 arg1 effect 982:987 significant protective effect 959:987 significant protective effect against H2O2-induced PC12 cell injury 959:1025 Cs-GP1 exhibited remarkable antioxidant capacity with a Trolox equivalent antioxidant capacity of 1183.8 μmol/g and a ferric reducing ability of 611.1 μmol Fe(II)/g, and significant protective effect against H2O2-induced PC12 cell injury at a minimum dose of 10 μg/mL. 25268609 5 32 theme Fe 945:946 arg1 ability 923:929 a ferric reducing ability 905:929 a ferric reducing ability of 611.1 μmol Fe(II)/g 905:952 Cs-GP1 exhibited remarkable antioxidant capacity with a Trolox equivalent antioxidant capacity of 1183.8 μmol/g and a ferric reducing ability of 611.1 μmol Fe(II)/g, and significant protective effect against H2O2-induced PC12 cell injury at a minimum dose of 10 μg/mL. 25268609 6 33 from structure 1090:1098 arg1 species 1168:1174 the Cordyceps species 1154:1174 the Cordyceps species 1154:1174 This is the first report on the structure and bioactivity of an extracellular glycopeptide from the Cordyceps species. 25268609 5 34 theme μmol 940:943 arg1 Fe 945:946 611.1 μmol Fe(II)/g 934:952 611.1 μmol Fe(II)/g 934:952 Cs-GP1 exhibited remarkable antioxidant capacity with a Trolox equivalent antioxidant capacity of 1183.8 μmol/g and a ferric reducing ability of 611.1 μmol Fe(II)/g, and significant protective effect against H2O2-induced PC12 cell injury at a minimum dose of 10 μg/mL. 25268609 0 35 from broth 96:100 arg1 structure 14:22 structure 14:22 structure 14:22 Isolation and structure characterization of an antioxidative glycopeptide from mycelial culture broth of a medicinal fungus. 25268609 0 35 from broth 96:100 arg1 Isolation 0:8 Isolation 0:8 Isolation 0:8 Isolation and structure characterization of an antioxidative glycopeptide from mycelial culture broth of a medicinal fungus. 25268609 3 36 theme high 533:536 arg1 ratios 543:548 relatively high mole ratios 522:548 relatively high mole ratios of aspartic acid, glutamic acid and glycine (3.3-3.5 relative to arginine) 522:623 The peptide chain contained relatively high mole ratios of aspartic acid, glutamic acid and glycine (3.3-3.5 relative to arginine) but relatively low ratios of tyrosine and histidine. 25268609 5 37 dep capacity 829:836 arg1 capacity 875:882 equivalent antioxidant capacity 852:882 remarkable antioxidant capacity with a Trolox equivalent antioxidant capacity of 1183.8 μmol/g 806:899 Cs-GP1 exhibited remarkable antioxidant capacity with a Trolox equivalent antioxidant capacity of 1183.8 μmol/g and a ferric reducing ability of 611.1 μmol Fe(II)/g, and significant protective effect against H2O2-induced PC12 cell injury at a minimum dose of 10 μg/mL. 25268609 6 38 gly glycopeptide 1136:1147 arg1 species 1168:1174 the Cordyceps species 1154:1174 the Cordyceps species 1154:1174 This is the first report on the structure and bioactivity of an extracellular glycopeptide from the Cordyceps species. 25268609 6 38 gly glycopeptide 1136:1147 arg2 glycopeptide 1136:1147 an extracellular glycopeptide 1119:1147 an extracellular glycopeptide from the Cordyceps species 1119:1174 This is the first report on the structure and bioactivity of an extracellular glycopeptide from the Cordyceps species. 25268609 1 39 theme lower 264:268 arg1 fraction 273:280 the lower Mw fraction 260:280 the lower Mw fraction of exopolysaccharide (EPS) produced by a medicinal fungus Cordyceps sinensis Cs-HK1 260:364 A novel glycopeptide (Cs-GP1) with an average molecular weight (Mw) of 6.0 kDa was isolated and purified by column chromatography from the lower Mw fraction of exopolysaccharide (EPS) produced by a medicinal fungus Cordyceps sinensis Cs-HK1. 25268609 1 40 gly glycopeptide 133:144 arg2 Cs-GP1 147:152 Cs-GP1 147:152 Cs-GP1 147:152 A novel glycopeptide (Cs-GP1) with an average molecular weight (Mw) of 6.0 kDa was isolated and purified by column chromatography from the lower Mw fraction of exopolysaccharide (EPS) produced by a medicinal fungus Cordyceps sinensis Cs-HK1. 25268609 1 40 gly glycopeptide 133:144 arg2 glycopeptide 133:144 A novel glycopeptide 125:144 A novel glycopeptide (Cs-GP1) with an average molecular weight (Mw) of 6.0 kDa 125:202 A novel glycopeptide (Cs-GP1) with an average molecular weight (Mw) of 6.0 kDa was isolated and purified by column chromatography from the lower Mw fraction of exopolysaccharide (EPS) produced by a medicinal fungus Cordyceps sinensis Cs-HK1. 25268609 1 41 theme sinensis 350:357 arg1 Cs-HK1 359:364 a medicinal fungus Cordyceps sinensis Cs-HK1 321:364 a medicinal fungus Cordyceps sinensis Cs-HK1 321:364 A novel glycopeptide (Cs-GP1) with an average molecular weight (Mw) of 6.0 kDa was isolated and purified by column chromatography from the lower Mw fraction of exopolysaccharide (EPS) produced by a medicinal fungus Cordyceps sinensis Cs-HK1. 25268609 3 42 theme acid 562:565 arg1 ratios 543:548 relatively high mole ratios 522:548 relatively high mole ratios of aspartic acid, glutamic acid and glycine (3.3-3.5 relative to arginine) 522:623 The peptide chain contained relatively high mole ratios of aspartic acid, glutamic acid and glycine (3.3-3.5 relative to arginine) but relatively low ratios of tyrosine and histidine. 25268609 2 43 theme mole 445:448 arg1 ratio 450:454 3.2:1.0 mole ratio 437:454 3.2:1.0 mole ratio 437:454 Its carbohydrate moiety was mainly composed of glucose and mannose at 3.2:1.0 mole ratio, indicating an O-linked glycopeptide. 25268609 2 44 theme carbohydrate 371:382 arg1 moiety 384:389 Its carbohydrate moiety 367:389 Its carbohydrate moiety 367:389 Its carbohydrate moiety was mainly composed of glucose and mannose at 3.2:1.0 mole ratio, indicating an O-linked glycopeptide. 25268609 1 45 theme Mw 270:271 arg1 fraction 273:280 the lower Mw fraction 260:280 the lower Mw fraction of exopolysaccharide (EPS) produced by a medicinal fungus Cordyceps sinensis Cs-HK1 260:364 A novel glycopeptide (Cs-GP1) with an average molecular weight (Mw) of 6.0 kDa was isolated and purified by column chromatography from the lower Mw fraction of exopolysaccharide (EPS) produced by a medicinal fungus Cordyceps sinensis Cs-HK1. 25268609 5 46 theme H2O2-induced 997:1008 arg1 injury 1020:1025 H2O2-induced PC12 cell injury 997:1025 H2O2-induced PC12 cell injury 997:1025 Cs-GP1 exhibited remarkable antioxidant capacity with a Trolox equivalent antioxidant capacity of 1183.8 μmol/g and a ferric reducing ability of 611.1 μmol Fe(II)/g, and significant protective effect against H2O2-induced PC12 cell injury at a minimum dose of 10 μg/mL. 25268609 6 47 from report 1076:1081 arg1 bioactivity 1104:1114 bioactivity 1104:1114 bioactivity 1104:1114 This is the first report on the structure and bioactivity of an extracellular glycopeptide from the Cordyceps species. 25268609 6 47 from report 1076:1081 arg1 structure 1090:1098 structure 1090:1098 structure 1090:1098 This is the first report on the structure and bioactivity of an extracellular glycopeptide from the Cordyceps species. 25268609 3 48 dep glycine 586:592 arg1 3.3-3.5 595:601 3.3-3.5 595:601 3.3-3.5 595:601 The peptide chain contained relatively high mole ratios of aspartic acid, glutamic acid and glycine (3.3-3.5 relative to arginine) but relatively low ratios of tyrosine and histidine. 25268609 0 49 theme glycopeptide 61:72 arg1 structure 14:22 structure 14:22 structure 14:22 Isolation and structure characterization of an antioxidative glycopeptide from mycelial culture broth of a medicinal fungus. 25268609 0 49 theme glycopeptide 61:72 arg1 Isolation 0:8 Isolation 0:8 Isolation 0:8 Isolation and structure characterization of an antioxidative glycopeptide from mycelial culture broth of a medicinal fungus. 25268609 2 50 theme O-linked 471:478 arg1 glycopeptide 480:491 an O-linked glycopeptide 468:491 an O-linked glycopeptide 468:491 Its carbohydrate moiety was mainly composed of glucose and mannose at 3.2:1.0 mole ratio, indicating an O-linked glycopeptide. 25268609 5 51 theme antioxidant 817:827 arg1 capacity 829:836 remarkable antioxidant capacity 806:836 remarkable antioxidant capacity with a Trolox equivalent antioxidant capacity of 1183.8 μmol/g 806:899 Cs-GP1 exhibited remarkable antioxidant capacity with a Trolox equivalent antioxidant capacity of 1183.8 μmol/g and a ferric reducing ability of 611.1 μmol Fe(II)/g, and significant protective effect against H2O2-induced PC12 cell injury at a minimum dose of 10 μg/mL. 25268609 5 52 theme μg/mL 1051:1055 arg1 dose 1040:1043 a minimum dose 1030:1043 a minimum dose of 10 μg/mL 1030:1055 Cs-GP1 exhibited remarkable antioxidant capacity with a Trolox equivalent antioxidant capacity of 1183.8 μmol/g and a ferric reducing ability of 611.1 μmol Fe(II)/g, and significant protective effect against H2O2-induced PC12 cell injury at a minimum dose of 10 μg/mL. 25268609 5 53 theme PC12 1010:1013 arg1 injury 1020:1025 H2O2-induced PC12 cell injury 997:1025 H2O2-induced PC12 cell injury 997:1025 Cs-GP1 exhibited remarkable antioxidant capacity with a Trolox equivalent antioxidant capacity of 1183.8 μmol/g and a ferric reducing ability of 611.1 μmol Fe(II)/g, and significant protective effect against H2O2-induced PC12 cell injury at a minimum dose of 10 μg/mL. 25268609 5 54 theme ferric 907:912 arg1 ability 923:929 a ferric reducing ability 905:929 a ferric reducing ability of 611.1 μmol Fe(II)/g 905:952 Cs-GP1 exhibited remarkable antioxidant capacity with a Trolox equivalent antioxidant capacity of 1183.8 μmol/g and a ferric reducing ability of 611.1 μmol Fe(II)/g, and significant protective effect against H2O2-induced PC12 cell injury at a minimum dose of 10 μg/mL. 25268609 0 55 theme antioxidative 47:59 arg1 glycopeptide 61:72 an antioxidative glycopeptide 44:72 an antioxidative glycopeptide 44:72 Isolation and structure characterization of an antioxidative glycopeptide from mycelial culture broth of a medicinal fungus. 25268609 3 56 contain contained 512:520 arg1 chain 506:510 The peptide chain 494:510 The peptide chain 494:510 The peptide chain contained relatively high mole ratios of aspartic acid, glutamic acid and glycine (3.3-3.5 relative to arginine) but relatively low ratios of tyrosine and histidine. 25268609 3 56 contain contained 512:520 arg2 ratios 543:548 relatively high mole ratios 522:548 relatively high mole ratios of aspartic acid, glutamic acid and glycine (3.3-3.5 relative to arginine) 522:623 The peptide chain contained relatively high mole ratios of aspartic acid, glutamic acid and glycine (3.3-3.5 relative to arginine) but relatively low ratios of tyrosine and histidine. 25268609 3 56 contain contained 512:520 arg2 ratios 644:649 relatively low ratios 629:649 relatively low ratios of tyrosine and histidine 629:675 The peptide chain contained relatively high mole ratios of aspartic acid, glutamic acid and glycine (3.3-3.5 relative to arginine) but relatively low ratios of tyrosine and histidine. 25268609 3 57 theme aspartic 553:560 arg1 acid 562:565 aspartic acid 553:565 aspartic acid 553:565 The peptide chain contained relatively high mole ratios of aspartic acid, glutamic acid and glycine (3.3-3.5 relative to arginine) but relatively low ratios of tyrosine and histidine. 25268609 5 58 theme reducing 914:921 arg1 ability 923:929 a ferric reducing ability 905:929 a ferric reducing ability of 611.1 μmol Fe(II)/g 905:952 Cs-GP1 exhibited remarkable antioxidant capacity with a Trolox equivalent antioxidant capacity of 1183.8 μmol/g and a ferric reducing ability of 611.1 μmol Fe(II)/g, and significant protective effect against H2O2-induced PC12 cell injury at a minimum dose of 10 μg/mL. 25268609 1 59 theme exopolysaccharide 285:301 arg1 fraction 273:280 the lower Mw fraction 260:280 the lower Mw fraction of exopolysaccharide (EPS) produced by a medicinal fungus Cordyceps sinensis Cs-HK1 260:364 A novel glycopeptide (Cs-GP1) with an average molecular weight (Mw) of 6.0 kDa was isolated and purified by column chromatography from the lower Mw fraction of exopolysaccharide (EPS) produced by a medicinal fungus Cordyceps sinensis Cs-HK1. 25268609 0 60 gly glycopeptide 61:72 arg2 glycopeptide 61:72 an antioxidative glycopeptide 44:72 an antioxidative glycopeptide 44:72 Isolation and structure characterization of an antioxidative glycopeptide from mycelial culture broth of a medicinal fungus. 25268609 1 61 theme novel 127:131 arg1 Cs-GP1 147:152 Cs-GP1 147:152 Cs-GP1 147:152 A novel glycopeptide (Cs-GP1) with an average molecular weight (Mw) of 6.0 kDa was isolated and purified by column chromatography from the lower Mw fraction of exopolysaccharide (EPS) produced by a medicinal fungus Cordyceps sinensis Cs-HK1. 25268609 1 61 theme novel 127:131 arg1 glycopeptide 133:144 A novel glycopeptide 125:144 A novel glycopeptide (Cs-GP1) with an average molecular weight (Mw) of 6.0 kDa 125:202 A novel glycopeptide (Cs-GP1) with an average molecular weight (Mw) of 6.0 kDa was isolated and purified by column chromatography from the lower Mw fraction of exopolysaccharide (EPS) produced by a medicinal fungus Cordyceps sinensis Cs-HK1. 25268609 2 62 from ratio 450:454 arg1 mannose 426:432 mannose 426:432 mannose 426:432 Its carbohydrate moiety was mainly composed of glucose and mannose at 3.2:1.0 mole ratio, indicating an O-linked glycopeptide. 25268609 2 62 from ratio 450:454 arg1 glucose 414:420 glucose 414:420 glucose 414:420 Its carbohydrate moiety was mainly composed of glucose and mannose at 3.2:1.0 mole ratio, indicating an O-linked glycopeptide. 25268609 3 63 theme glycine 586:592 arg1 ratios 543:548 relatively high mole ratios 522:548 relatively high mole ratios of aspartic acid, glutamic acid and glycine (3.3-3.5 relative to arginine) 522:623 The peptide chain contained relatively high mole ratios of aspartic acid, glutamic acid and glycine (3.3-3.5 relative to arginine) but relatively low ratios of tyrosine and histidine. 25268609 2 64 link O-linked 471:478 arg1 glycopeptide 480:491 an O-linked glycopeptide 468:491 an O-linked glycopeptide 468:491 Its carbohydrate moiety was mainly composed of glucose and mannose at 3.2:1.0 mole ratio, indicating an O-linked glycopeptide. 25268609 6 65 theme first 1070:1074 arg1 report 1076:1081 the first report 1066:1081 the first report on the structure and bioactivity of an extracellular glycopeptide from the Cordyceps species 1066:1174 This is the first report on the structure and bioactivity of an extracellular glycopeptide from the Cordyceps species. 25268609 6 65 theme first 1070:1074 arg1 This 1058:1061 This 1058:1061 This 1058:1061 This is the first report on the structure and bioactivity of an extracellular glycopeptide from the Cordyceps species. 25268609 1 66 theme kDa 200:202 arg1 Mw 189:190 Mw 189:190 Mw 189:190 A novel glycopeptide (Cs-GP1) with an average molecular weight (Mw) of 6.0 kDa was isolated and purified by column chromatography from the lower Mw fraction of exopolysaccharide (EPS) produced by a medicinal fungus Cordyceps sinensis Cs-HK1. 25268609 1 66 theme kDa 200:202 arg1 weight 181:186 an average molecular weight 160:186 an average molecular weight (Mw) of 6.0 kDa 160:202 A novel glycopeptide (Cs-GP1) with an average molecular weight (Mw) of 6.0 kDa was isolated and purified by column chromatography from the lower Mw fraction of exopolysaccharide (EPS) produced by a medicinal fungus Cordyceps sinensis Cs-HK1. 25268609 0 67 theme mycelial 79:86 arg1 broth 96:100 mycelial culture broth 79:100 mycelial culture broth of a medicinal fungus 79:122 Isolation and structure characterization of an antioxidative glycopeptide from mycelial culture broth of a medicinal fungus. 25268609 5 68 theme minimum 1032:1038 arg1 dose 1040:1043 a minimum dose 1030:1043 a minimum dose of 10 μg/mL 1030:1055 Cs-GP1 exhibited remarkable antioxidant capacity with a Trolox equivalent antioxidant capacity of 1183.8 μmol/g and a ferric reducing ability of 611.1 μmol Fe(II)/g, and significant protective effect against H2O2-induced PC12 cell injury at a minimum dose of 10 μg/mL. 25268609 3 69 theme glutamic 568:575 arg1 acid 577:580 glutamic acid 568:580 glutamic acid 568:580 The peptide chain contained relatively high mole ratios of aspartic acid, glutamic acid and glycine (3.3-3.5 relative to arginine) but relatively low ratios of tyrosine and histidine. 25268609 6 70 from bioactivity 1104:1114 arg1 species 1168:1174 the Cordyceps species 1154:1174 the Cordyceps species 1154:1174 This is the first report on the structure and bioactivity of an extracellular glycopeptide from the Cordyceps species. 25268609 5 71 theme antioxidant 863:873 arg1 capacity 875:882 equivalent antioxidant capacity 852:882 remarkable antioxidant capacity with a Trolox equivalent antioxidant capacity of 1183.8 μmol/g 806:899 Cs-GP1 exhibited remarkable antioxidant capacity with a Trolox equivalent antioxidant capacity of 1183.8 μmol/g and a ferric reducing ability of 611.1 μmol Fe(II)/g, and significant protective effect against H2O2-induced PC12 cell injury at a minimum dose of 10 μg/mL. 25268609 5 72 with effect 982:987 arg1 Trolox 845:850 a Trolox 843:850 a Trolox 843:850 Cs-GP1 exhibited remarkable antioxidant capacity with a Trolox equivalent antioxidant capacity of 1183.8 μmol/g and a ferric reducing ability of 611.1 μmol Fe(II)/g, and significant protective effect against H2O2-induced PC12 cell injury at a minimum dose of 10 μg/mL. 25268609 0 73 dep Isolation 0:8 arg1 characterization 24:39 characterization 24:39 characterization 24:39 Isolation and structure characterization of an antioxidative glycopeptide from mycelial culture broth of a medicinal fungus. 25268609 5 74 theme μmol/g 894:899 arg1 capacity 829:836 remarkable antioxidant capacity 806:836 remarkable antioxidant capacity with a Trolox equivalent antioxidant capacity of 1183.8 μmol/g 806:899 Cs-GP1 exhibited remarkable antioxidant capacity with a Trolox equivalent antioxidant capacity of 1183.8 μmol/g and a ferric reducing ability of 611.1 μmol Fe(II)/g, and significant protective effect against H2O2-induced PC12 cell injury at a minimum dose of 10 μg/mL. 25268609 5 74 theme μmol/g 894:899 arg1 effect 982:987 significant protective effect 959:987 significant protective effect against H2O2-induced PC12 cell injury 959:1025 Cs-GP1 exhibited remarkable antioxidant capacity with a Trolox equivalent antioxidant capacity of 1183.8 μmol/g and a ferric reducing ability of 611.1 μmol Fe(II)/g, and significant protective effect against H2O2-induced PC12 cell injury at a minimum dose of 10 μg/mL. 25268609 5 74 theme μmol/g 894:899 arg1 ability 923:929 a ferric reducing ability 905:929 a ferric reducing ability of 611.1 μmol Fe(II)/g 905:952 Cs-GP1 exhibited remarkable antioxidant capacity with a Trolox equivalent antioxidant capacity of 1183.8 μmol/g and a ferric reducing ability of 611.1 μmol Fe(II)/g, and significant protective effect against H2O2-induced PC12 cell injury at a minimum dose of 10 μg/mL. 27542620 0 0 theme M1 94:95 arg1 polarization 108:119 M1 macrophage polarization 94:119 M1 macrophage polarization 94:119 Modification of TAK1 by O-linked N-acetylglucosamine facilitates TAK1 activation and promotes M1 macrophage polarization. 27542620 8 1 from apoptosis 1463:1471 arg1 macrophages 1476:1486 macrophages 1476:1486 macrophages 1476:1486 Results also showed that overexpression of the O-GlcNAcylation-deficient mutant of TAK1 promotes LPS-mediated apoptosis in macrophages. 27542620 6 2 from O-GlcNAcylation 1005:1019 arg1 S427 1032:1035 S427 1032:1035 S427 1032:1035 By overexpressing wild-type (WT) or S427A TAK1 mutant into macrophages, it was determined that O-GlcNAcylation of TAK1 on S427 is required for T187/S192 phosphorylation and full activation of TAK1 upon stimulation with IL-1α and NaCl. 27542620 9 3 theme macrophage 1547:1556 arg1 polarization 1558:1569 M1 macrophage polarization 1544:1569 M1 macrophage polarization 1544:1569 Importantly, TAK1 O-GlcNAcylation was found to promote M1 macrophage polarization in activated macrophages. 27542620 1 4 theme acute 270:274 arg1 responses 289:297 acute inflammatory responses 270:297 acute inflammatory responses 270:297 Macrophages play many different roles in tissue inflammation and immunity, and the plasticity of macrophage polarization is closely associated with acute inflammatory responses. 27542620 10 5 from O-GlcNAcylation 1641:1655 arg1 S427 1668:1671 S427 1668:1671 S427 1668:1671 Taken together, these data demonstrate that O-GlcNAcylation of TAK1 on S427 critically regulates the pro-inflammatory activation and M1 polarization of macrophages via modulation of the TAK1/JNK/NF-κB signaling pathway. 27542620 3 6 dep factor 440:445 arg1 kinase 465:470 -β-activated kinase 1 452:472 Transforming growth factor (TGF)-β-activated kinase 1 (TAK1) 420:479 Transforming growth factor (TGF)-β-activated kinase 1 (TAK1) is a key serine/threonine protein kinase that mediates signals transduced by pro-inflammatory cytokines such as TGF-β, tumor necrosis factor (TNF), and interleukin-1 (IL-1). 27542620 3 6 dep factor 440:445 arg1 TAK1 475:478 TAK1 475:478 TAK1 475:478 Transforming growth factor (TGF)-β-activated kinase 1 (TAK1) is a key serine/threonine protein kinase that mediates signals transduced by pro-inflammatory cytokines such as TGF-β, tumor necrosis factor (TNF), and interleukin-1 (IL-1). 27542620 2 7 theme inflammation 396:407 arg1 responses 409:417 inflammation responses 396:417 inflammation responses 396:417 O-GlcNAcylation is an important type of post-translational modification, which subtly modulates inflammation responses. 27542620 4 8 mod modified 712:719 arg3 O-GlcNAc 747:754 O-GlcNAc 747:754 O-GlcNAc 747:754 It is here reported that TGFβ-activated kinase (TAK1) is modified with N-acetylglucosamine (O-GlcNAc) on S427. 27542620 4 8 mod modified 712:719 arg1 TAK1 703:706 TAK1 703:706 TAK1 703:706 It is here reported that TGFβ-activated kinase (TAK1) is modified with N-acetylglucosamine (O-GlcNAc) on S427. 27542620 4 8 mod modified 712:719 arg3 N-acetylglucosamine 726:744 N-acetylglucosamine 726:744 N-acetylglucosamine (O-GlcNAc) on S427 726:763 It is here reported that TGFβ-activated kinase (TAK1) is modified with N-acetylglucosamine (O-GlcNAc) on S427. 27542620 4 8 mod modified 712:719 arg1 kinase 695:700 TGFβ-activated kinase 680:700 TGFβ-activated kinase (TAK1) 680:707 It is here reported that TGFβ-activated kinase (TAK1) is modified with N-acetylglucosamine (O-GlcNAc) on S427. 27542620 1 9 theme inflammatory 276:287 arg1 responses 289:297 acute inflammatory responses 270:297 acute inflammatory responses 270:297 Macrophages play many different roles in tissue inflammation and immunity, and the plasticity of macrophage polarization is closely associated with acute inflammatory responses. 27542620 2 10 theme important 322:330 arg1 O-GlcNAcylation 300:314 O-GlcNAcylation 300:314 O-GlcNAcylation 300:314 O-GlcNAcylation is an important type of post-translational modification, which subtly modulates inflammation responses. 27542620 2 10 theme important 322:330 arg1 type 332:335 an important type 319:335 an important type 319:335 O-GlcNAcylation is an important type of post-translational modification, which subtly modulates inflammation responses. 27542620 0 11 theme macrophage 97:106 arg1 polarization 108:119 M1 macrophage polarization 94:119 M1 macrophage polarization 94:119 Modification of TAK1 by O-linked N-acetylglucosamine facilitates TAK1 activation and promotes M1 macrophage polarization. 27542620 7 12 from O-GlcNAcylation 1154:1168 arg1 S427 1181:1184 S427 1181:1184 S427 1181:1184 Aborting O-GlcNAcylation of TAK1 on S427 was found to inhibit the downstream JNK and nuclear factor-κB activation and reduce the final amount of cytokines produced in activated macrophages to a great extent. 27542620 7 13 theme nuclear 1230:1236 arg1 activation 1248:1257 the downstream JNK and nuclear factor-κB activation 1207:1257 activation 1248:1257 Aborting O-GlcNAcylation of TAK1 on S427 was found to inhibit the downstream JNK and nuclear factor-κB activation and reduce the final amount of cytokines produced in activated macrophages to a great extent. 27542620 9 14 theme activated 1574:1582 arg1 macrophages 1584:1594 activated macrophages 1574:1594 activated macrophages 1574:1594 Importantly, TAK1 O-GlcNAcylation was found to promote M1 macrophage polarization in activated macrophages. 27542620 6 15 dep wild-type 928:936 arg1 mutant 957:962 mutant 957:962 mutant 957:962 By overexpressing wild-type (WT) or S427A TAK1 mutant into macrophages, it was determined that O-GlcNAcylation of TAK1 on S427 is required for T187/S192 phosphorylation and full activation of TAK1 upon stimulation with IL-1α and NaCl. 27542620 6 15 dep wild-type 928:936 arg1 WT 939:940 WT 939:940 WT 939:940 By overexpressing wild-type (WT) or S427A TAK1 mutant into macrophages, it was determined that O-GlcNAcylation of TAK1 on S427 is required for T187/S192 phosphorylation and full activation of TAK1 upon stimulation with IL-1α and NaCl. 27542620 10 16 theme M1 1730:1731 arg1 polarization 1733:1744 M1 polarization 1730:1744 M1 polarization 1730:1744 Taken together, these data demonstrate that O-GlcNAcylation of TAK1 on S427 critically regulates the pro-inflammatory activation and M1 polarization of macrophages via modulation of the TAK1/JNK/NF-κB signaling pathway. 27542620 10 17 theme pro-inflammatory 1698:1713 arg1 activation 1715:1724 pro-inflammatory activation 1698:1724 pro-inflammatory activation 1698:1724 Taken together, these data demonstrate that O-GlcNAcylation of TAK1 on S427 critically regulates the pro-inflammatory activation and M1 polarization of macrophages via modulation of the TAK1/JNK/NF-κB signaling pathway. 27542620 10 18 theme pathway 1808:1814 arg1 modulation 1765:1774 modulation 1765:1774 modulation of the TAK1/JNK/NF-κB signaling pathway 1765:1814 Taken together, these data demonstrate that O-GlcNAcylation of TAK1 on S427 critically regulates the pro-inflammatory activation and M1 polarization of macrophages via modulation of the TAK1/JNK/NF-κB signaling pathway. 27542620 6 19 theme full 1083:1086 arg1 activation 1088:1097 full activation 1083:1097 full activation of TAK1 upon stimulation with IL-1α and NaCl 1083:1142 By overexpressing wild-type (WT) or S427A TAK1 mutant into macrophages, it was determined that O-GlcNAcylation of TAK1 on S427 is required for T187/S192 phosphorylation and full activation of TAK1 upon stimulation with IL-1α and NaCl. 27542620 7 20 theme TAK1 1173:1176 arg1 O-GlcNAcylation 1154:1168 Aborting O-GlcNAcylation 1145:1168 Aborting O-GlcNAcylation of TAK1 on S427 1145:1184 Aborting O-GlcNAcylation of TAK1 on S427 was found to inhibit the downstream JNK and nuclear factor-κB activation and reduce the final amount of cytokines produced in activated macrophages to a great extent. 27542620 2 21 theme modification 359:370 arg1 O-GlcNAcylation 300:314 O-GlcNAcylation 300:314 O-GlcNAcylation 300:314 O-GlcNAcylation is an important type of post-translational modification, which subtly modulates inflammation responses. 27542620 2 21 theme modification 359:370 arg1 type 332:335 an important type 319:335 an important type 319:335 O-GlcNAcylation is an important type of post-translational modification, which subtly modulates inflammation responses. 27542620 6 22 theme T187/S192 1053:1061 arg1 phosphorylation 1063:1077 T187/S192 phosphorylation 1053:1077 T187/S192 phosphorylation 1053:1077 By overexpressing wild-type (WT) or S427A TAK1 mutant into macrophages, it was determined that O-GlcNAcylation of TAK1 on S427 is required for T187/S192 phosphorylation and full activation of TAK1 upon stimulation with IL-1α and NaCl. 27542620 2 23 theme post-translational 340:357 arg1 modification 359:370 post-translational modification 340:370 post-translational modification 340:370 O-GlcNAcylation is an important type of post-translational modification, which subtly modulates inflammation responses. 27542620 4 24 theme TGFβ-activated 680:693 arg1 TAK1 703:706 TAK1 703:706 TAK1 703:706 It is here reported that TGFβ-activated kinase (TAK1) is modified with N-acetylglucosamine (O-GlcNAc) on S427. 27542620 4 24 theme TGFβ-activated 680:693 arg1 kinase 695:700 TGFβ-activated kinase 680:700 TGFβ-activated kinase (TAK1) 680:707 It is here reported that TGFβ-activated kinase (TAK1) is modified with N-acetylglucosamine (O-GlcNAc) on S427. 27542620 3 25 theme growth 433:438 arg1 kinase 515:520 a key serine/threonine protein kinase 484:520 a key serine/threonine protein kinase that mediates signals transduced by pro-inflammatory cytokines such as TGF-β, tumor necrosis factor (TNF), and interleukin-1 (IL-1) 484:652 Transforming growth factor (TGF)-β-activated kinase 1 (TAK1) is a key serine/threonine protein kinase that mediates signals transduced by pro-inflammatory cytokines such as TGF-β, tumor necrosis factor (TNF), and interleukin-1 (IL-1). 27542620 3 25 theme growth 433:438 arg1 TGF 448:450 TGF 448:450 TGF 448:450 Transforming growth factor (TGF)-β-activated kinase 1 (TAK1) is a key serine/threonine protein kinase that mediates signals transduced by pro-inflammatory cytokines such as TGF-β, tumor necrosis factor (TNF), and interleukin-1 (IL-1). 27542620 3 25 theme growth 433:438 arg1 factor 440:445 Transforming growth factor 420:445 Transforming growth factor (TGF)-β-activated kinase 1 (TAK1) 420:479 Transforming growth factor (TGF)-β-activated kinase 1 (TAK1) is a key serine/threonine protein kinase that mediates signals transduced by pro-inflammatory cytokines such as TGF-β, tumor necrosis factor (TNF), and interleukin-1 (IL-1). 27542620 9 26 theme TAK1 1502:1505 arg1 O-GlcNAcylation 1507:1521 TAK1 O-GlcNAcylation 1502:1521 TAK1 O-GlcNAcylation 1502:1521 Importantly, TAK1 O-GlcNAcylation was found to promote M1 macrophage polarization in activated macrophages. 27542620 10 27 theme TAK1/JNK/NF-κB 1783:1796 arg1 pathway 1808:1814 the TAK1/JNK/NF-κB signaling pathway 1779:1814 the TAK1/JNK/NF-κB signaling pathway 1779:1814 Taken together, these data demonstrate that O-GlcNAcylation of TAK1 on S427 critically regulates the pro-inflammatory activation and M1 polarization of macrophages via modulation of the TAK1/JNK/NF-κB signaling pathway. 27542620 0 28 link O-linked 24:31 arg1 N-acetylglucosamine 33:51 O-linked N-acetylglucosamine 24:51 O-linked N-acetylglucosamine 24:51 Modification of TAK1 by O-linked N-acetylglucosamine facilitates TAK1 activation and promotes M1 macrophage polarization. 27542620 3 29 theme tumor 600:604 arg1 TNF 623:625 TNF 623:625 TNF 623:625 Transforming growth factor (TGF)-β-activated kinase 1 (TAK1) is a key serine/threonine protein kinase that mediates signals transduced by pro-inflammatory cytokines such as TGF-β, tumor necrosis factor (TNF), and interleukin-1 (IL-1). 27542620 3 29 theme tumor 600:604 arg1 factor 615:620 tumor necrosis factor 600:620 tumor necrosis factor (TNF) 600:626 Transforming growth factor (TGF)-β-activated kinase 1 (TAK1) is a key serine/threonine protein kinase that mediates signals transduced by pro-inflammatory cytokines such as TGF-β, tumor necrosis factor (TNF), and interleukin-1 (IL-1). 27542620 3 30 theme serine/threonine 490:505 arg1 kinase 515:520 a key serine/threonine protein kinase 484:520 a key serine/threonine protein kinase that mediates signals transduced by pro-inflammatory cytokines such as TGF-β, tumor necrosis factor (TNF), and interleukin-1 (IL-1) 484:652 Transforming growth factor (TGF)-β-activated kinase 1 (TAK1) is a key serine/threonine protein kinase that mediates signals transduced by pro-inflammatory cytokines such as TGF-β, tumor necrosis factor (TNF), and interleukin-1 (IL-1). 27542620 3 30 theme serine/threonine 490:505 arg1 factor 440:445 Transforming growth factor 420:445 Transforming growth factor (TGF)-β-activated kinase 1 (TAK1) 420:479 Transforming growth factor (TGF)-β-activated kinase 1 (TAK1) is a key serine/threonine protein kinase that mediates signals transduced by pro-inflammatory cytokines such as TGF-β, tumor necrosis factor (TNF), and interleukin-1 (IL-1). 27542620 0 31 theme TAK1 16:19 arg1 Modification 0:11 Modification 0:11 Modification of TAK1 by O-linked N-acetylglucosamine 0:51 Modification of TAK1 by O-linked N-acetylglucosamine facilitates TAK1 activation and promotes M1 macrophage polarization. 27542620 10 32 theme signaling 1798:1806 arg1 pathway 1808:1814 the TAK1/JNK/NF-κB signaling pathway 1779:1814 the TAK1/JNK/NF-κB signaling pathway 1779:1814 Taken together, these data demonstrate that O-GlcNAcylation of TAK1 on S427 critically regulates the pro-inflammatory activation and M1 polarization of macrophages via modulation of the TAK1/JNK/NF-κB signaling pathway. 27542620 3 33 theme necrosis 606:613 arg1 TNF 623:625 TNF 623:625 TNF 623:625 Transforming growth factor (TGF)-β-activated kinase 1 (TAK1) is a key serine/threonine protein kinase that mediates signals transduced by pro-inflammatory cytokines such as TGF-β, tumor necrosis factor (TNF), and interleukin-1 (IL-1). 27542620 3 33 theme necrosis 606:613 arg1 factor 615:620 tumor necrosis factor 600:620 tumor necrosis factor (TNF) 600:626 Transforming growth factor (TGF)-β-activated kinase 1 (TAK1) is a key serine/threonine protein kinase that mediates signals transduced by pro-inflammatory cytokines such as TGF-β, tumor necrosis factor (TNF), and interleukin-1 (IL-1). 27542620 3 34 theme protein 507:513 arg1 kinase 515:520 a key serine/threonine protein kinase 484:520 a key serine/threonine protein kinase that mediates signals transduced by pro-inflammatory cytokines such as TGF-β, tumor necrosis factor (TNF), and interleukin-1 (IL-1) 484:652 Transforming growth factor (TGF)-β-activated kinase 1 (TAK1) is a key serine/threonine protein kinase that mediates signals transduced by pro-inflammatory cytokines such as TGF-β, tumor necrosis factor (TNF), and interleukin-1 (IL-1). 27542620 3 34 theme protein 507:513 arg1 factor 440:445 Transforming growth factor 420:445 Transforming growth factor (TGF)-β-activated kinase 1 (TAK1) 420:479 Transforming growth factor (TGF)-β-activated kinase 1 (TAK1) is a key serine/threonine protein kinase that mediates signals transduced by pro-inflammatory cytokines such as TGF-β, tumor necrosis factor (TNF), and interleukin-1 (IL-1). 27542620 5 35 theme osmotic 780:786 arg1 IL-1 771:774 IL-1 771:774 IL-1 771:774 Both IL-1 and osmotic stress, which are known as the TAK1-signaling inducers, significantly trigger the O-GlcNAcylation of TAK1 in macrophages. 27542620 5 35 theme osmotic 780:786 arg1 stress 788:793 osmotic stress 780:793 osmotic stress 780:793 Both IL-1 and osmotic stress, which are known as the TAK1-signaling inducers, significantly trigger the O-GlcNAcylation of TAK1 in macrophages. 27542620 5 35 theme osmotic 780:786 arg1 inducers 834:841 the TAK1-signaling inducers 815:841 the TAK1-signaling inducers 815:841 Both IL-1 and osmotic stress, which are known as the TAK1-signaling inducers, significantly trigger the O-GlcNAcylation of TAK1 in macrophages. 27542620 7 36 theme final 1274:1278 arg1 cytokines 1290:1298 cytokines 1290:1298 cytokines produced in activated macrophages to a great extent 1290:1350 Aborting O-GlcNAcylation of TAK1 on S427 was found to inhibit the downstream JNK and nuclear factor-κB activation and reduce the final amount of cytokines produced in activated macrophages to a great extent. 27542620 7 36 theme final 1274:1278 arg1 amount 1280:1285 the final amount 1270:1285 the final amount of cytokines produced in activated macrophages to a great extent 1270:1350 Aborting O-GlcNAcylation of TAK1 on S427 was found to inhibit the downstream JNK and nuclear factor-κB activation and reduce the final amount of cytokines produced in activated macrophages to a great extent. 27542620 7 37 theme factor-κB 1238:1246 arg1 activation 1248:1257 the downstream JNK and nuclear factor-κB activation 1207:1257 activation 1248:1257 Aborting O-GlcNAcylation of TAK1 on S427 was found to inhibit the downstream JNK and nuclear factor-κB activation and reduce the final amount of cytokines produced in activated macrophages to a great extent. 27542620 7 38 theme activated 1312:1320 arg1 macrophages 1322:1332 activated macrophages 1312:1332 activated macrophages 1312:1332 Aborting O-GlcNAcylation of TAK1 on S427 was found to inhibit the downstream JNK and nuclear factor-κB activation and reduce the final amount of cytokines produced in activated macrophages to a great extent. 27542620 1 39 theme macrophage 219:228 arg1 polarization 230:241 macrophage polarization 219:241 macrophage polarization 219:241 Macrophages play many different roles in tissue inflammation and immunity, and the plasticity of macrophage polarization is closely associated with acute inflammatory responses. 27542620 0 40 theme O-linked 24:31 arg1 N-acetylglucosamine 33:51 O-linked N-acetylglucosamine 24:51 O-linked N-acetylglucosamine 24:51 Modification of TAK1 by O-linked N-acetylglucosamine facilitates TAK1 activation and promotes M1 macrophage polarization. 27542620 7 41 theme Aborting 1145:1152 arg1 O-GlcNAcylation 1154:1168 Aborting O-GlcNAcylation 1145:1168 Aborting O-GlcNAcylation of TAK1 on S427 1145:1184 Aborting O-GlcNAcylation of TAK1 on S427 was found to inhibit the downstream JNK and nuclear factor-κB activation and reduce the final amount of cytokines produced in activated macrophages to a great extent. 27542620 6 42 dep S427A 946:950 arg1 TAK1 952:955 S427A TAK1 946:955 S427A TAK1 946:955 By overexpressing wild-type (WT) or S427A TAK1 mutant into macrophages, it was determined that O-GlcNAcylation of TAK1 on S427 is required for T187/S192 phosphorylation and full activation of TAK1 upon stimulation with IL-1α and NaCl. 27542620 10 43 dep activation 1715:1724 arg1 the 1694:1696 the 1694:1696 the 1694:1696 Taken together, these data demonstrate that O-GlcNAcylation of TAK1 on S427 critically regulates the pro-inflammatory activation and M1 polarization of macrophages via modulation of the TAK1/JNK/NF-κB signaling pathway. 27542620 1 44 theme polarization 230:241 arg1 plasticity 205:214 the plasticity 201:214 the plasticity of macrophage polarization 201:241 Macrophages play many different roles in tissue inflammation and immunity, and the plasticity of macrophage polarization is closely associated with acute inflammatory responses. 27542620 0 45 theme TAK1 65:68 arg1 activation 70:79 TAK1 activation 65:79 TAK1 activation 65:79 Modification of TAK1 by O-linked N-acetylglucosamine facilitates TAK1 activation and promotes M1 macrophage polarization. 27542620 5 46 theme TAK1 889:892 arg1 O-GlcNAcylation 870:884 the O-GlcNAcylation 866:884 the O-GlcNAcylation of TAK1 in macrophages 866:907 Both IL-1 and osmotic stress, which are known as the TAK1-signaling inducers, significantly trigger the O-GlcNAcylation of TAK1 in macrophages. 27542620 8 47 theme O-GlcNAcylation-deficient 1400:1424 arg1 mutant 1426:1431 the O-GlcNAcylation-deficient mutant 1396:1431 the O-GlcNAcylation-deficient mutant of TAK1 1396:1439 Results also showed that overexpression of the O-GlcNAcylation-deficient mutant of TAK1 promotes LPS-mediated apoptosis in macrophages. 27542620 6 48 theme TAK1 1102:1105 arg1 phosphorylation 1063:1077 T187/S192 phosphorylation 1053:1077 T187/S192 phosphorylation 1053:1077 By overexpressing wild-type (WT) or S427A TAK1 mutant into macrophages, it was determined that O-GlcNAcylation of TAK1 on S427 is required for T187/S192 phosphorylation and full activation of TAK1 upon stimulation with IL-1α and NaCl. 27542620 6 48 theme TAK1 1102:1105 arg1 activation 1088:1097 full activation 1083:1097 full activation of TAK1 upon stimulation with IL-1α and NaCl 1083:1142 By overexpressing wild-type (WT) or S427A TAK1 mutant into macrophages, it was determined that O-GlcNAcylation of TAK1 on S427 is required for T187/S192 phosphorylation and full activation of TAK1 upon stimulation with IL-1α and NaCl. 27542620 3 49 theme -β-activated 452:463 arg1 kinase 465:470 -β-activated kinase 1 452:472 Transforming growth factor (TGF)-β-activated kinase 1 (TAK1) 420:479 Transforming growth factor (TGF)-β-activated kinase 1 (TAK1) is a key serine/threonine protein kinase that mediates signals transduced by pro-inflammatory cytokines such as TGF-β, tumor necrosis factor (TNF), and interleukin-1 (IL-1). 27542620 3 49 theme -β-activated 452:463 arg1 TAK1 475:478 TAK1 475:478 TAK1 475:478 Transforming growth factor (TGF)-β-activated kinase 1 (TAK1) is a key serine/threonine protein kinase that mediates signals transduced by pro-inflammatory cytokines such as TGF-β, tumor necrosis factor (TNF), and interleukin-1 (IL-1). 27542620 1 50 theme many 139:142 arg1 roles 154:158 many different roles 139:158 many different roles 139:158 Macrophages play many different roles in tissue inflammation and immunity, and the plasticity of macrophage polarization is closely associated with acute inflammatory responses. 27542620 8 51 theme LPS-mediated 1450:1461 arg1 apoptosis 1463:1471 LPS-mediated apoptosis 1450:1471 LPS-mediated apoptosis in macrophages 1450:1486 Results also showed that overexpression of the O-GlcNAcylation-deficient mutant of TAK1 promotes LPS-mediated apoptosis in macrophages. 27542620 8 52 theme TAK1 1436:1439 arg1 mutant 1426:1431 the O-GlcNAcylation-deficient mutant 1396:1431 the O-GlcNAcylation-deficient mutant of TAK1 1396:1439 Results also showed that overexpression of the O-GlcNAcylation-deficient mutant of TAK1 promotes LPS-mediated apoptosis in macrophages. 27542620 1 53 theme different 144:152 arg1 roles 154:158 many different roles 139:158 many different roles 139:158 Macrophages play many different roles in tissue inflammation and immunity, and the plasticity of macrophage polarization is closely associated with acute inflammatory responses. 27542620 4 54 from N-acetylglucosamine 726:744 arg1 S427 760:763 S427 760:763 S427 760:763 It is here reported that TGFβ-activated kinase (TAK1) is modified with N-acetylglucosamine (O-GlcNAc) on S427. 27542620 6 55 theme TAK1 1024:1027 arg1 O-GlcNAcylation 1005:1019 O-GlcNAcylation 1005:1019 O-GlcNAcylation of TAK1 on S427 1005:1035 By overexpressing wild-type (WT) or S427A TAK1 mutant into macrophages, it was determined that O-GlcNAcylation of TAK1 on S427 is required for T187/S192 phosphorylation and full activation of TAK1 upon stimulation with IL-1α and NaCl. 27542620 8 56 theme mutant 1426:1431 arg1 overexpression 1378:1391 overexpression 1378:1391 overexpression of the O-GlcNAcylation-deficient mutant of TAK1 1378:1439 Results also showed that overexpression of the O-GlcNAcylation-deficient mutant of TAK1 promotes LPS-mediated apoptosis in macrophages. 27542620 5 57 from O-GlcNAcylation 870:884 arg1 macrophages 897:907 macrophages 897:907 macrophages 897:907 Both IL-1 and osmotic stress, which are known as the TAK1-signaling inducers, significantly trigger the O-GlcNAcylation of TAK1 in macrophages. 27542620 9 58 theme M1 1544:1545 arg1 polarization 1558:1569 M1 macrophage polarization 1544:1569 M1 macrophage polarization 1544:1569 Importantly, TAK1 O-GlcNAcylation was found to promote M1 macrophage polarization in activated macrophages. 27542620 10 59 theme macrophages 1749:1759 arg1 activation 1715:1724 pro-inflammatory activation 1698:1724 pro-inflammatory activation 1698:1724 Taken together, these data demonstrate that O-GlcNAcylation of TAK1 on S427 critically regulates the pro-inflammatory activation and M1 polarization of macrophages via modulation of the TAK1/JNK/NF-κB signaling pathway. 27542620 10 59 theme macrophages 1749:1759 arg1 polarization 1733:1744 M1 polarization 1730:1744 M1 polarization 1730:1744 Taken together, these data demonstrate that O-GlcNAcylation of TAK1 on S427 critically regulates the pro-inflammatory activation and M1 polarization of macrophages via modulation of the TAK1/JNK/NF-κB signaling pathway. 27542620 7 60 theme downstream 1211:1220 arg1 JNK 1222:1224 the downstream JNK and nuclear factor-κB activation 1207:1257 JNK 1222:1224 Aborting O-GlcNAcylation of TAK1 on S427 was found to inhibit the downstream JNK and nuclear factor-κB activation and reduce the final amount of cytokines produced in activated macrophages to a great extent. 27542620 3 61 theme key 486:488 arg1 kinase 515:520 a key serine/threonine protein kinase 484:520 a key serine/threonine protein kinase that mediates signals transduced by pro-inflammatory cytokines such as TGF-β, tumor necrosis factor (TNF), and interleukin-1 (IL-1) 484:652 Transforming growth factor (TGF)-β-activated kinase 1 (TAK1) is a key serine/threonine protein kinase that mediates signals transduced by pro-inflammatory cytokines such as TGF-β, tumor necrosis factor (TNF), and interleukin-1 (IL-1). 27542620 3 61 theme key 486:488 arg1 factor 440:445 Transforming growth factor 420:445 Transforming growth factor (TGF)-β-activated kinase 1 (TAK1) 420:479 Transforming growth factor (TGF)-β-activated kinase 1 (TAK1) is a key serine/threonine protein kinase that mediates signals transduced by pro-inflammatory cytokines such as TGF-β, tumor necrosis factor (TNF), and interleukin-1 (IL-1). 27542620 5 62 theme TAK1-signaling 819:832 arg1 IL-1 771:774 IL-1 771:774 IL-1 771:774 Both IL-1 and osmotic stress, which are known as the TAK1-signaling inducers, significantly trigger the O-GlcNAcylation of TAK1 in macrophages. 27542620 5 62 theme TAK1-signaling 819:832 arg1 inducers 834:841 the TAK1-signaling inducers 815:841 the TAK1-signaling inducers 815:841 Both IL-1 and osmotic stress, which are known as the TAK1-signaling inducers, significantly trigger the O-GlcNAcylation of TAK1 in macrophages. 27542620 5 62 theme TAK1-signaling 819:832 arg1 stress 788:793 osmotic stress 780:793 osmotic stress 780:793 Both IL-1 and osmotic stress, which are known as the TAK1-signaling inducers, significantly trigger the O-GlcNAcylation of TAK1 in macrophages. 27542620 3 63 theme pro-inflammatory 558:573 arg1 TGF-β 593:597 TGF-β 593:597 TGF-β 593:597 Transforming growth factor (TGF)-β-activated kinase 1 (TAK1) is a key serine/threonine protein kinase that mediates signals transduced by pro-inflammatory cytokines such as TGF-β, tumor necrosis factor (TNF), and interleukin-1 (IL-1). 27542620 3 63 theme pro-inflammatory 558:573 arg1 factor 615:620 tumor necrosis factor 600:620 tumor necrosis factor (TNF) 600:626 Transforming growth factor (TGF)-β-activated kinase 1 (TAK1) is a key serine/threonine protein kinase that mediates signals transduced by pro-inflammatory cytokines such as TGF-β, tumor necrosis factor (TNF), and interleukin-1 (IL-1). 27542620 3 63 theme pro-inflammatory 558:573 arg1 interleukin-1 633:645 interleukin-1 633:645 interleukin-1 (IL-1) 633:652 Transforming growth factor (TGF)-β-activated kinase 1 (TAK1) is a key serine/threonine protein kinase that mediates signals transduced by pro-inflammatory cytokines such as TGF-β, tumor necrosis factor (TNF), and interleukin-1 (IL-1). 27542620 3 63 theme pro-inflammatory 558:573 arg1 cytokines 575:583 pro-inflammatory cytokines 558:583 pro-inflammatory cytokines such as TGF-β, tumor necrosis factor (TNF), and interleukin-1 (IL-1) 558:652 Transforming growth factor (TGF)-β-activated kinase 1 (TAK1) is a key serine/threonine protein kinase that mediates signals transduced by pro-inflammatory cytokines such as TGF-β, tumor necrosis factor (TNF), and interleukin-1 (IL-1). 27542620 7 64 theme cytokines 1290:1298 arg1 cytokines 1290:1298 cytokines 1290:1298 cytokines produced in activated macrophages to a great extent 1290:1350 Aborting O-GlcNAcylation of TAK1 on S427 was found to inhibit the downstream JNK and nuclear factor-κB activation and reduce the final amount of cytokines produced in activated macrophages to a great extent. 27542620 7 64 theme cytokines 1290:1298 arg1 amount 1280:1285 the final amount 1270:1285 the final amount of cytokines produced in activated macrophages to a great extent 1270:1350 Aborting O-GlcNAcylation of TAK1 on S427 was found to inhibit the downstream JNK and nuclear factor-κB activation and reduce the final amount of cytokines produced in activated macrophages to a great extent. 27542620 10 65 theme TAK1 1660:1663 arg1 O-GlcNAcylation 1641:1655 O-GlcNAcylation 1641:1655 O-GlcNAcylation of TAK1 on S427 1641:1671 Taken together, these data demonstrate that O-GlcNAcylation of TAK1 on S427 critically regulates the pro-inflammatory activation and M1 polarization of macrophages via modulation of the TAK1/JNK/NF-κB signaling pathway. 27542620 6 66 with stimulation 1112:1122 arg1 NaCl 1139:1142 NaCl 1139:1142 NaCl 1139:1142 By overexpressing wild-type (WT) or S427A TAK1 mutant into macrophages, it was determined that O-GlcNAcylation of TAK1 on S427 is required for T187/S192 phosphorylation and full activation of TAK1 upon stimulation with IL-1α and NaCl. 27542620 6 66 with stimulation 1112:1122 arg1 IL-1α 1129:1133 IL-1α 1129:1133 IL-1α 1129:1133 By overexpressing wild-type (WT) or S427A TAK1 mutant into macrophages, it was determined that O-GlcNAcylation of TAK1 on S427 is required for T187/S192 phosphorylation and full activation of TAK1 upon stimulation with IL-1α and NaCl. 27542620 7 67 theme great 1339:1343 arg1 extent 1345:1350 a great extent 1337:1350 a great extent 1337:1350 Aborting O-GlcNAcylation of TAK1 on S427 was found to inhibit the downstream JNK and nuclear factor-κB activation and reduce the final amount of cytokines produced in activated macrophages to a great extent. 27542620 1 68 theme tissue 163:168 arg1 inflammation 170:181 tissue inflammation 163:181 tissue inflammation 163:181 Macrophages play many different roles in tissue inflammation and immunity, and the plasticity of macrophage polarization is closely associated with acute inflammatory responses. 27542620 3 69 theme Transforming 420:431 arg1 kinase 515:520 a key serine/threonine protein kinase 484:520 a key serine/threonine protein kinase that mediates signals transduced by pro-inflammatory cytokines such as TGF-β, tumor necrosis factor (TNF), and interleukin-1 (IL-1) 484:652 Transforming growth factor (TGF)-β-activated kinase 1 (TAK1) is a key serine/threonine protein kinase that mediates signals transduced by pro-inflammatory cytokines such as TGF-β, tumor necrosis factor (TNF), and interleukin-1 (IL-1). 27542620 3 69 theme Transforming 420:431 arg1 TGF 448:450 TGF 448:450 TGF 448:450 Transforming growth factor (TGF)-β-activated kinase 1 (TAK1) is a key serine/threonine protein kinase that mediates signals transduced by pro-inflammatory cytokines such as TGF-β, tumor necrosis factor (TNF), and interleukin-1 (IL-1). 27542620 3 69 theme Transforming 420:431 arg1 factor 440:445 Transforming growth factor 420:445 Transforming growth factor (TGF)-β-activated kinase 1 (TAK1) 420:479 Transforming growth factor (TGF)-β-activated kinase 1 (TAK1) is a key serine/threonine protein kinase that mediates signals transduced by pro-inflammatory cytokines such as TGF-β, tumor necrosis factor (TNF), and interleukin-1 (IL-1). 26744353 11 0 theme model 1320:1324 arg1 establishment 1284:1296 a successful establishment 1271:1296 a successful establishment of a new chick embryo model to study the molecular mechanism of hyperglycemia-induced eye malformation 1271:1399 These results illustrated a successful establishment of a new chick embryo model to study the molecular mechanism of hyperglycemia-induced eye malformation. 26744353 12 1 theme gene 1430:1433 arg1 suppression 1406:1416 The suppression 1402:1416 The suppression of the Pax6 gene 1402:1433 The suppression of the Pax6 gene is probably mediated by oxidative stress and could be a crucial target for the therapy of GDM-induced embryonic eye malformation. 26744353 5 2 theme key 604:606 arg1 Six3 648:651 Six3 648:651 Six3 648:651 In this model, the key genes regulating eye development, Pax6, Six3 and Otx2, were downregulated by hyperglycemia. 26744353 5 2 theme key 604:606 arg1 Pax6 642:645 Pax6 642:645 Pax6 642:645 In this model, the key genes regulating eye development, Pax6, Six3 and Otx2, were downregulated by hyperglycemia. 26744353 5 2 theme key 604:606 arg1 genes 608:612 the key genes 600:612 the key genes regulating eye development 600:639 In this model, the key genes regulating eye development, Pax6, Six3 and Otx2, were downregulated by hyperglycemia. 26744353 5 2 theme key 604:606 arg1 Otx2 657:660 Otx2 657:660 Otx2 657:660 In this model, the key genes regulating eye development, Pax6, Six3 and Otx2, were downregulated by hyperglycemia. 26744353 7 3 theme Pax6 824:827 arg1 expression 834:843 Pax6 gene expression 824:843 Pax6 gene expression 824:843 A reduction in Pax6 gene expression induced eye malformation in chick embryos. 26744353 3 4 theme embryo 445:450 arg1 EDD 469:471 EDD 469:471 EDD 469:471 In this study, a high concentration of glucose (0.2 mmol per egg) was injected into the air sac of chick embryos on embryo development day (EDD) 1 to develop a hyperglycemia model. 26744353 3 4 theme embryo 445:450 arg1 day 464:466 embryo development day 445:466 embryo development day (EDD) 1 445:474 In this study, a high concentration of glucose (0.2 mmol per egg) was injected into the air sac of chick embryos on embryo development day (EDD) 1 to develop a hyperglycemia model. 26744353 12 5 theme Pax6 1425:1428 arg1 gene 1430:1433 the Pax6 gene 1421:1433 the Pax6 gene 1421:1433 The suppression of the Pax6 gene is probably mediated by oxidative stress and could be a crucial target for the therapy of GDM-induced embryonic eye malformation. 26744353 0 6 theme Pax6 100:103 arg1 inhibition 86:95 inhibition 86:95 inhibition of Pax6 in the chick embryo 86:123 A new gestational diabetes mellitus model: hyperglycemia-induced eye malformation via inhibition of Pax6 in the chick embryo. 26744353 7 7 theme gene 829:832 arg1 expression 834:843 Pax6 gene expression 824:843 Pax6 gene expression 824:843 A reduction in Pax6 gene expression induced eye malformation in chick embryos. 26744353 3 8 theme development 452:462 arg1 EDD 469:471 EDD 469:471 EDD 469:471 In this study, a high concentration of glucose (0.2 mmol per egg) was injected into the air sac of chick embryos on embryo development day (EDD) 1 to develop a hyperglycemia model. 26744353 3 8 theme development 452:462 arg1 day 464:466 embryo development day 445:466 embryo development day (EDD) 1 445:474 In this study, a high concentration of glucose (0.2 mmol per egg) was injected into the air sac of chick embryos on embryo development day (EDD) 1 to develop a hyperglycemia model. 26744353 12 9 theme oxidative 1459:1467 arg1 stress 1469:1474 oxidative stress 1459:1474 oxidative stress 1459:1474 The suppression of the Pax6 gene is probably mediated by oxidative stress and could be a crucial target for the therapy of GDM-induced embryonic eye malformation. 26744353 4 10 theme embryonic 539:547 arg1 malformation 553:564 embryonic eye malformation 539:564 embryonic eye malformation 539:564 Results showed that 47.3% of embryonic eye malformation happened on EDD 5. 26744353 3 11 dep concentration 351:363 arg1 0.2 mmol 377:384 0.2 mmol 377:384 0.2 mmol per egg 377:392 In this study, a high concentration of glucose (0.2 mmol per egg) was injected into the air sac of chick embryos on embryo development day (EDD) 1 to develop a hyperglycemia model. 26744353 11 12 theme molecular 1339:1347 arg1 mechanism 1349:1357 the molecular mechanism 1335:1357 the molecular mechanism of hyperglycemia-induced eye malformation 1335:1399 These results illustrated a successful establishment of a new chick embryo model to study the molecular mechanism of hyperglycemia-induced eye malformation. 26744353 2 13 theme GDM-induced 293:303 arg1 malformation 315:326 GDM-induced fetal eye malformation 293:326 GDM-induced fetal eye malformation 293:326 However, few models have been developed to study the underlying mechanisms of GDM-induced fetal eye malformation. 26744353 11 14 theme chick 1307:1311 arg1 model 1320:1324 a new chick embryo model 1301:1324 a new chick embryo model 1301:1324 These results illustrated a successful establishment of a new chick embryo model to study the molecular mechanism of hyperglycemia-induced eye malformation. 26744353 3 15 theme chick 428:432 arg1 embryos 434:440 chick embryos 428:440 chick embryos 428:440 In this study, a high concentration of glucose (0.2 mmol per egg) was injected into the air sac of chick embryos on embryo development day (EDD) 1 to develop a hyperglycemia model. 26744353 8 16 theme Pax6 921:924 arg1 expression 907:916 increased expression 897:916 increased expression of Pax6 in chick embryos 897:941 However, increased expression of Pax6 in chick embryos could rescue hyperglycemia-induced eye malformation. 26744353 3 17 theme air 417:419 arg1 sac 421:423 the air sac 413:423 the air sac of chick embryos on embryo development day (EDD) 1 413:474 In this study, a high concentration of glucose (0.2 mmol per egg) was injected into the air sac of chick embryos on embryo development day (EDD) 1 to develop a hyperglycemia model. 26744353 8 18 theme increased 897:905 arg1 expression 907:916 increased expression 897:916 increased expression of Pax6 in chick embryos 897:941 However, increased expression of Pax6 in chick embryos could rescue hyperglycemia-induced eye malformation. 26744353 3 19 from sac 421:423 arg1 EDD 469:471 EDD 469:471 EDD 469:471 In this study, a high concentration of glucose (0.2 mmol per egg) was injected into the air sac of chick embryos on embryo development day (EDD) 1 to develop a hyperglycemia model. 26744353 3 19 from sac 421:423 arg1 day 464:466 embryo development day 445:466 embryo development day (EDD) 1 445:474 In this study, a high concentration of glucose (0.2 mmol per egg) was injected into the air sac of chick embryos on embryo development day (EDD) 1 to develop a hyperglycemia model. 26744353 0 20 theme new 2:4 arg1 model 36:40 A new gestational diabetes mellitus model 0:40 A new gestational diabetes mellitus model: hyperglycemia-induced eye malformation via inhibition of Pax6 in the chick embryo. 0:124 A new gestational diabetes mellitus model: hyperglycemia-induced eye malformation via inhibition of Pax6 in the chick embryo. 26744353 8 21 theme chick 929:933 arg1 embryos 935:941 chick embryos 929:941 chick embryos 929:941 However, increased expression of Pax6 in chick embryos could rescue hyperglycemia-induced eye malformation. 26744353 10 22 theme antioxidant 1163:1173 arg1 edaravone 1175:1183 the antioxidant edaravone 1159:1183 the antioxidant edaravone 1159:1183 Pax6 was found to be vulnerable to free radicals, but the antioxidant edaravone could restore Pax6 expression and reverse eye malformation. 26744353 9 23 theme chick 1090:1094 arg1 embryos 1096:1102 chick embryos 1090:1102 chick embryos 1090:1102 Hyperglycemia stimulated O-linked N-acetylglucosaminylation, which caused oxidative stress in chick embryos. 26744353 8 24 from expression 907:916 arg1 embryos 935:941 chick embryos 929:941 chick embryos 929:941 However, increased expression of Pax6 in chick embryos could rescue hyperglycemia-induced eye malformation. 26744353 3 25 theme hyperglycemia 489:501 arg1 model 503:507 a hyperglycemia model 487:507 a hyperglycemia model 487:507 In this study, a high concentration of glucose (0.2 mmol per egg) was injected into the air sac of chick embryos on embryo development day (EDD) 1 to develop a hyperglycemia model. 26744353 11 26 theme eye 1384:1386 arg1 malformation 1388:1399 hyperglycemia-induced eye malformation 1362:1399 hyperglycemia-induced eye malformation 1362:1399 These results illustrated a successful establishment of a new chick embryo model to study the molecular mechanism of hyperglycemia-induced eye malformation. 26744353 0 27 theme diabetes 18:25 arg1 mellitus 27:34 gestational diabetes mellitus 6:34 A new gestational diabetes mellitus model: hyperglycemia-induced eye malformation via inhibition of Pax6 in the chick embryo. 0:124 A new gestational diabetes mellitus model: hyperglycemia-induced eye malformation via inhibition of Pax6 in the chick embryo. 26744353 12 28 theme embryonic 1537:1545 arg1 malformation 1551:1562 GDM-induced embryonic eye malformation 1525:1562 GDM-induced embryonic eye malformation 1525:1562 The suppression of the Pax6 gene is probably mediated by oxidative stress and could be a crucial target for the therapy of GDM-induced embryonic eye malformation. 26744353 2 29 theme underlying 268:277 arg1 mechanisms 279:288 the underlying mechanisms 264:288 the underlying mechanisms of GDM-induced fetal eye malformation 264:326 However, few models have been developed to study the underlying mechanisms of GDM-induced fetal eye malformation. 26744353 11 30 theme malformation 1388:1399 arg1 mechanism 1349:1357 the molecular mechanism 1335:1357 the molecular mechanism of hyperglycemia-induced eye malformation 1335:1399 These results illustrated a successful establishment of a new chick embryo model to study the molecular mechanism of hyperglycemia-induced eye malformation. 26744353 4 31 theme eye 549:551 arg1 malformation 553:564 embryonic eye malformation 539:564 embryonic eye malformation 539:564 Results showed that 47.3% of embryonic eye malformation happened on EDD 5. 26744353 0 32 theme gestational 6:16 arg1 mellitus 27:34 gestational diabetes mellitus 6:34 A new gestational diabetes mellitus model: hyperglycemia-induced eye malformation via inhibition of Pax6 in the chick embryo. 0:124 A new gestational diabetes mellitus model: hyperglycemia-induced eye malformation via inhibition of Pax6 in the chick embryo. 26744353 12 33 theme GDM-induced 1525:1535 arg1 malformation 1551:1562 GDM-induced embryonic eye malformation 1525:1562 GDM-induced embryonic eye malformation 1525:1562 The suppression of the Pax6 gene is probably mediated by oxidative stress and could be a crucial target for the therapy of GDM-induced embryonic eye malformation. 26744353 0 34 theme chick 112:116 arg1 embryo 118:123 the chick embryo 108:123 the chick embryo 108:123 A new gestational diabetes mellitus model: hyperglycemia-induced eye malformation via inhibition of Pax6 in the chick embryo. 26744353 0 35 from inhibition 86:95 arg1 embryo 118:123 the chick embryo 108:123 the chick embryo 108:123 A new gestational diabetes mellitus model: hyperglycemia-induced eye malformation via inhibition of Pax6 in the chick embryo. 26744353 7 36 from reduction 811:819 arg1 expression 834:843 Pax6 gene expression 824:843 Pax6 gene expression 824:843 A reduction in Pax6 gene expression induced eye malformation in chick embryos. 26744353 1 37 theme leading 176:182 arg1 causes 184:189 the leading causes 172:189 the leading causes of fetal malformations 172:212 Gestational diabetes mellitus (GDM) is one of the leading causes of fetal malformations. 26744353 11 38 theme hyperglycemia-induced 1362:1382 arg1 malformation 1388:1399 hyperglycemia-induced eye malformation 1362:1399 hyperglycemia-induced eye malformation 1362:1399 These results illustrated a successful establishment of a new chick embryo model to study the molecular mechanism of hyperglycemia-induced eye malformation. 26744353 3 39 theme embryos 434:440 arg1 sac 421:423 the air sac 413:423 the air sac of chick embryos on embryo development day (EDD) 1 413:474 In this study, a high concentration of glucose (0.2 mmol per egg) was injected into the air sac of chick embryos on embryo development day (EDD) 1 to develop a hyperglycemia model. 26744353 8 40 theme hyperglycemia-induced 956:976 arg1 malformation 982:993 hyperglycemia-induced eye malformation 956:993 hyperglycemia-induced eye malformation 956:993 However, increased expression of Pax6 in chick embryos could rescue hyperglycemia-induced eye malformation. 26744353 10 41 theme Pax6 1199:1202 arg1 expression 1204:1213 Pax6 expression 1199:1213 Pax6 expression 1199:1213 Pax6 was found to be vulnerable to free radicals, but the antioxidant edaravone could restore Pax6 expression and reverse eye malformation. 26744353 1 42 theme causes 184:189 arg1 one 165:167 one 165:167 one 165:167 Gestational diabetes mellitus (GDM) is one of the leading causes of fetal malformations. 26744353 1 42 theme causes 184:189 arg1 causes 184:189 the leading causes 172:189 the leading causes of fetal malformations 172:212 Gestational diabetes mellitus (GDM) is one of the leading causes of fetal malformations. 26744353 0 43 theme mellitus 27:34 arg1 model 36:40 A new gestational diabetes mellitus model 0:40 A new gestational diabetes mellitus model: hyperglycemia-induced eye malformation via inhibition of Pax6 in the chick embryo. 0:124 A new gestational diabetes mellitus model: hyperglycemia-induced eye malformation via inhibition of Pax6 in the chick embryo. 26744353 12 44 theme crucial 1491:1497 arg1 target 1499:1504 a crucial target 1489:1504 a crucial target for the therapy of GDM-induced embryonic eye malformation 1489:1562 The suppression of the Pax6 gene is probably mediated by oxidative stress and could be a crucial target for the therapy of GDM-induced embryonic eye malformation. 26744353 11 45 theme successful 1273:1282 arg1 establishment 1284:1296 a successful establishment 1271:1296 a successful establishment of a new chick embryo model to study the molecular mechanism of hyperglycemia-induced eye malformation 1271:1399 These results illustrated a successful establishment of a new chick embryo model to study the molecular mechanism of hyperglycemia-induced eye malformation. 26744353 6 46 theme Pax6 737:740 arg1 expression 723:732 the expression 719:732 the expression of Pax6 719:740 Among these genes, the expression of Pax6 was the most vulnerable to hyperglycemia, being suppressed by 70%. 26744353 6 46 theme Pax6 737:740 arg1 vulnerable 755:764 vulnerable 755:764 vulnerable 755:764 Among these genes, the expression of Pax6 was the most vulnerable to hyperglycemia, being suppressed by 70%. 26744353 11 47 theme embryo 1313:1318 arg1 model 1320:1324 a new chick embryo model 1301:1324 a new chick embryo model 1301:1324 These results illustrated a successful establishment of a new chick embryo model to study the molecular mechanism of hyperglycemia-induced eye malformation. 26744353 4 48 theme malformation 553:564 arg1 malformation 553:564 embryonic eye malformation 539:564 embryonic eye malformation 539:564 Results showed that 47.3% of embryonic eye malformation happened on EDD 5. 26744353 4 48 theme malformation 553:564 arg1 % 534:534 47.3% 530:534 47.3% of embryonic eye malformation 530:564 Results showed that 47.3% of embryonic eye malformation happened on EDD 5. 26744353 0 49 theme hyperglycemia-induced 43:63 arg1 malformation 69:80 hyperglycemia-induced eye malformation 43:80 A new gestational diabetes mellitus model: hyperglycemia-induced eye malformation via inhibition of Pax6 in the chick embryo. 0:124 A new gestational diabetes mellitus model: hyperglycemia-induced eye malformation via inhibition of Pax6 in the chick embryo. 26744353 5 50 theme eye 625:627 arg1 development 629:639 eye development 625:639 eye development 625:639 In this model, the key genes regulating eye development, Pax6, Six3 and Otx2, were downregulated by hyperglycemia. 26744353 12 51 theme eye 1547:1549 arg1 malformation 1551:1562 GDM-induced embryonic eye malformation 1525:1562 GDM-induced embryonic eye malformation 1525:1562 The suppression of the Pax6 gene is probably mediated by oxidative stress and could be a crucial target for the therapy of GDM-induced embryonic eye malformation. 26744353 11 52 theme new 1303:1305 arg1 model 1320:1324 a new chick embryo model 1301:1324 a new chick embryo model 1301:1324 These results illustrated a successful establishment of a new chick embryo model to study the molecular mechanism of hyperglycemia-induced eye malformation. 26744353 0 53 dep model 36:40 arg1 malformation 69:80 hyperglycemia-induced eye malformation 43:80 A new gestational diabetes mellitus model: hyperglycemia-induced eye malformation via inhibition of Pax6 in the chick embryo. 0:124 A new gestational diabetes mellitus model: hyperglycemia-induced eye malformation via inhibition of Pax6 in the chick embryo. 26744353 9 54 theme O-linked 1021:1028 arg1 N-acetylglucosaminylation 1030:1054 O-linked N-acetylglucosaminylation 1021:1054 O-linked N-acetylglucosaminylation 1021:1054 Hyperglycemia stimulated O-linked N-acetylglucosaminylation, which caused oxidative stress in chick embryos. 26744353 2 55 theme malformation 315:326 arg1 mechanisms 279:288 the underlying mechanisms 264:288 the underlying mechanisms of GDM-induced fetal eye malformation 264:326 However, few models have been developed to study the underlying mechanisms of GDM-induced fetal eye malformation. 26744353 3 56 theme glucose 368:374 arg1 concentration 351:363 a high concentration 344:363 a high concentration of glucose (0.2 mmol per egg) 344:393 In this study, a high concentration of glucose (0.2 mmol per egg) was injected into the air sac of chick embryos on embryo development day (EDD) 1 to develop a hyperglycemia model. 26744353 8 57 theme eye 978:980 arg1 malformation 982:993 hyperglycemia-induced eye malformation 956:993 hyperglycemia-induced eye malformation 956:993 However, increased expression of Pax6 in chick embryos could rescue hyperglycemia-induced eye malformation. 26744353 2 58 theme eye 311:313 arg1 malformation 315:326 GDM-induced fetal eye malformation 293:326 GDM-induced fetal eye malformation 293:326 However, few models have been developed to study the underlying mechanisms of GDM-induced fetal eye malformation. 26744353 10 59 theme free 1140:1143 arg1 radicals 1145:1152 free radicals 1140:1152 free radicals 1140:1152 Pax6 was found to be vulnerable to free radicals, but the antioxidant edaravone could restore Pax6 expression and reverse eye malformation. 26744353 9 60 link O-linked 1021:1028 arg1 N-acetylglucosaminylation 1030:1054 O-linked N-acetylglucosaminylation 1021:1054 O-linked N-acetylglucosaminylation 1021:1054 Hyperglycemia stimulated O-linked N-acetylglucosaminylation, which caused oxidative stress in chick embryos. 26744353 7 61 theme chick 873:877 arg1 embryos 879:885 chick embryos 873:885 chick embryos 873:885 A reduction in Pax6 gene expression induced eye malformation in chick embryos. 26744353 2 62 theme fetal 305:309 arg1 malformation 315:326 GDM-induced fetal eye malformation 293:326 GDM-induced fetal eye malformation 293:326 However, few models have been developed to study the underlying mechanisms of GDM-induced fetal eye malformation. 26744353 1 63 theme fetal 194:198 arg1 malformations 200:212 fetal malformations 194:212 fetal malformations 194:212 Gestational diabetes mellitus (GDM) is one of the leading causes of fetal malformations. 26744353 10 64 theme eye 1227:1229 arg1 malformation 1231:1242 eye malformation 1227:1242 eye malformation 1227:1242 Pax6 was found to be vulnerable to free radicals, but the antioxidant edaravone could restore Pax6 expression and reverse eye malformation. 26744353 7 65 theme eye 853:855 arg1 malformation 857:868 eye malformation 853:868 eye malformation 853:868 A reduction in Pax6 gene expression induced eye malformation in chick embryos. 26744353 1 66 theme Gestational 126:136 arg1 mellitus 147:154 Gestational diabetes mellitus 126:154 Gestational diabetes mellitus (GDM) 126:160 Gestational diabetes mellitus (GDM) is one of the leading causes of fetal malformations. 26744353 1 66 theme Gestational 126:136 arg1 GDM 157:159 GDM 157:159 GDM 157:159 Gestational diabetes mellitus (GDM) is one of the leading causes of fetal malformations. 26744353 1 67 theme malformations 200:212 arg1 causes 184:189 the leading causes 172:189 the leading causes of fetal malformations 172:212 Gestational diabetes mellitus (GDM) is one of the leading causes of fetal malformations. 26744353 2 68 theme few 224:226 arg1 models 228:233 few models 224:233 few models 224:233 However, few models have been developed to study the underlying mechanisms of GDM-induced fetal eye malformation. 26744353 1 69 theme diabetes 138:145 arg1 mellitus 147:154 Gestational diabetes mellitus 126:154 Gestational diabetes mellitus (GDM) 126:160 Gestational diabetes mellitus (GDM) is one of the leading causes of fetal malformations. 26744353 1 69 theme diabetes 138:145 arg1 GDM 157:159 GDM 157:159 GDM 157:159 Gestational diabetes mellitus (GDM) is one of the leading causes of fetal malformations. 26744353 12 70 theme malformation 1551:1562 arg1 therapy 1514:1520 the therapy 1510:1520 the therapy of GDM-induced embryonic eye malformation 1510:1562 The suppression of the Pax6 gene is probably mediated by oxidative stress and could be a crucial target for the therapy of GDM-induced embryonic eye malformation. 26744353 0 71 theme eye 65:67 arg1 malformation 69:80 hyperglycemia-induced eye malformation 43:80 A new gestational diabetes mellitus model: hyperglycemia-induced eye malformation via inhibition of Pax6 in the chick embryo. 0:124 A new gestational diabetes mellitus model: hyperglycemia-induced eye malformation via inhibition of Pax6 in the chick embryo. 26744353 9 72 theme oxidative 1070:1078 arg1 stress 1080:1085 oxidative stress 1070:1085 oxidative stress 1070:1085 Hyperglycemia stimulated O-linked N-acetylglucosaminylation, which caused oxidative stress in chick embryos. 26744353 3 73 theme high 346:349 arg1 concentration 351:363 a high concentration 344:363 a high concentration of glucose (0.2 mmol per egg) 344:393 In this study, a high concentration of glucose (0.2 mmol per egg) was injected into the air sac of chick embryos on embryo development day (EDD) 1 to develop a hyperglycemia model. 26168491 2 0 theme protein-derived 451:465 arg1 GcMAF 497:501 GcMAF 497:501 GcMAF 497:501 In particular, IgA has an O-linked sugar chain similar to that in the group-specific component (Gc) protein, a precursor of the Gc protein-derived macrophage-activating factor (GcMAF). 26168491 2 0 theme protein-derived 451:465 arg1 factor 489:494 Gc protein-derived macrophage-activating factor 448:494 the Gc protein-derived macrophage-activating factor (GcMAF) 444:502 In particular, IgA has an O-linked sugar chain similar to that in the group-specific component (Gc) protein, a precursor of the Gc protein-derived macrophage-activating factor (GcMAF). 26168491 4 1 theme western 720:726 arg1 blotting 728:735 western blotting 720:735 western blotting using Helix pomatia agglutinin lectin 720:773 RESULTS We detected the positive band in degalactosylated/ desialylated bovine colostrum by western blotting using Helix pomatia agglutinin lectin. 26168491 2 2 theme O-linked 346:353 arg1 chain 361:365 an O-linked sugar chain 343:365 an O-linked sugar chain similar to that in the group-specific component (Gc) protein, a precursor of the Gc protein-derived macrophage-activating factor (GcMAF) 343:502 In particular, IgA has an O-linked sugar chain similar to that in the group-specific component (Gc) protein, a precursor of the Gc protein-derived macrophage-activating factor (GcMAF). 26168491 2 3 theme Gc 448:449 arg1 GcMAF 497:501 GcMAF 497:501 GcMAF 497:501 In particular, IgA has an O-linked sugar chain similar to that in the group-specific component (Gc) protein, a precursor of the Gc protein-derived macrophage-activating factor (GcMAF). 26168491 2 3 theme Gc 448:449 arg1 factor 489:494 Gc protein-derived macrophage-activating factor 448:494 the Gc protein-derived macrophage-activating factor (GcMAF) 444:502 In particular, IgA has an O-linked sugar chain similar to that in the group-specific component (Gc) protein, a precursor of the Gc protein-derived macrophage-activating factor (GcMAF). 26168491 7 4 theme GcMAF 1189:1193 arg1 use 1182:1184 the use 1178:1184 the use of GcMAF, degalactosylated/desialylated bovine colostrum 1178:1241 CONCLUSION Similar to the use of GcMAF, degalactosylated/desialylated bovine colostrum can be used as a potential macrophage activator for various immunotherapies. 26168491 5 5 theme macrophages 954:964 arg1 activity 886:893 the phagocytic activity 871:893 the phagocytic activity of mouse peritoneal macrophages in vitro and of intestinal macrophages 871:964 We also found that degalactosylated/ desialylated bovine colostrum could significantly enhance the phagocytic activity of mouse peritoneal macrophages in vitro and of intestinal macrophages in vivo. 26168491 6 6 theme cytokines 1078:1086 arg1 production 1051:1060 the production 1047:1060 the production of inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) 1047:1153 Besides, degalactosylated/desialylated bovine colostrum did not mediate the production of inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). 26168491 7 7 theme macrophage 1270:1279 arg1 activator 1281:1289 a potential macrophage activator 1258:1289 a potential macrophage activator for various immunotherapies 1258:1317 CONCLUSION Similar to the use of GcMAF, degalactosylated/desialylated bovine colostrum can be used as a potential macrophage activator for various immunotherapies. 26168491 7 7 theme macrophage 1270:1279 arg1 CONCLUSION 1156:1165 CONCLUSION 1156:1165 CONCLUSION Similar to the use of GcMAF, degalactosylated/desialylated bovine colostrum 1156:1241 CONCLUSION Similar to the use of GcMAF, degalactosylated/desialylated bovine colostrum can be used as a potential macrophage activator for various immunotherapies. 26168491 2 8 contain has 339:341 arg1 IgA 335:337 IgA 335:337 IgA 335:337 In particular, IgA has an O-linked sugar chain similar to that in the group-specific component (Gc) protein, a precursor of the Gc protein-derived macrophage-activating factor (GcMAF). 26168491 2 8 contain has 339:341 arg2 chain 361:365 an O-linked sugar chain 343:365 an O-linked sugar chain similar to that in the group-specific component (Gc) protein, a precursor of the Gc protein-derived macrophage-activating factor (GcMAF) 343:502 In particular, IgA has an O-linked sugar chain similar to that in the group-specific component (Gc) protein, a precursor of the Gc protein-derived macrophage-activating factor (GcMAF). 26168491 7 9 gly degalactosylated/desialylated 1196:1224 arg1 colostrum 1233:1241 degalactosylated/desialylated bovine colostrum 1196:1241 degalactosylated/desialylated bovine colostrum 1196:1241 CONCLUSION Similar to the use of GcMAF, degalactosylated/desialylated bovine colostrum can be used as a potential macrophage activator for various immunotherapies. 26168491 7 9 gly degalactosylated/desialylated 1196:1224 arg1 GcMAF 1189:1193 GcMAF 1189:1193 GcMAF 1189:1193 CONCLUSION Similar to the use of GcMAF, degalactosylated/desialylated bovine colostrum can be used as a potential macrophage activator for various immunotherapies. 26168491 3 10 theme present 512:518 arg1 study 520:524 the present study 508:524 the present study 508:524 In the present study, we investigated the macrophage-activating effects of degalactosylated/desialylated bovine colostrum. 26168491 6 11 theme inflammatory 1065:1076 arg1 cytokines 1078:1086 inflammatory cytokines 1065:1086 inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) 1065:1153 Besides, degalactosylated/desialylated bovine colostrum did not mediate the production of inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). 26168491 6 11 theme inflammatory 1065:1076 arg1 interleukin-1β 1132:1145 interleukin-1β 1132:1145 interleukin-1β (IL-1β) 1132:1153 Besides, degalactosylated/desialylated bovine colostrum did not mediate the production of inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). 26168491 6 11 theme inflammatory 1065:1076 arg1 factor-α 1111:1118 tumor necrosis factor-α 1096:1118 tumor necrosis factor-α (TNF-α) 1096:1126 Besides, degalactosylated/desialylated bovine colostrum did not mediate the production of inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). 26168491 2 12 link O-linked 346:353 arg1 chain 361:365 an O-linked sugar chain 343:365 an O-linked sugar chain similar to that in the group-specific component (Gc) protein, a precursor of the Gc protein-derived macrophage-activating factor (GcMAF) 343:502 In particular, IgA has an O-linked sugar chain similar to that in the group-specific component (Gc) protein, a precursor of the Gc protein-derived macrophage-activating factor (GcMAF). 26168491 4 13 gly desialylated 687:698 arg1 colostrum 707:715 degalactosylated/ desialylated bovine colostrum 669:715 degalactosylated/ desialylated bovine colostrum 669:715 RESULTS We detected the positive band in degalactosylated/ desialylated bovine colostrum by western blotting using Helix pomatia agglutinin lectin. 26168491 6 14 gly degalactosylated/desialylated 984:1012 arg1 colostrum 1021:1029 degalactosylated/desialylated bovine colostrum 984:1029 degalactosylated/desialylated bovine colostrum 984:1029 Besides, degalactosylated/desialylated bovine colostrum did not mediate the production of inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). 26168491 1 15 contain has 282:284 arg2 activity 310:317 potent immunomodulating activity 286:317 potent immunomodulating activity 286:317 BACKGROUND/AIM Colostrum contains antibodies, such as immunoglobulin G (IgG), immunoglobulin A (IgA) and immunoglobulin M (IgM), and, therefore, has potent immunomodulating activity. 26168491 1 15 contain has 282:284 arg1 Colostrum 152:160 BACKGROUND/AIM Colostrum 137:160 BACKGROUND/AIM Colostrum 137:160 BACKGROUND/AIM Colostrum contains antibodies, such as immunoglobulin G (IgG), immunoglobulin A (IgA) and immunoglobulin M (IgM), and, therefore, has potent immunomodulating activity. 26168491 5 16 theme degalactosylated/ 795:811 arg1 colostrum 833:841 degalactosylated/ desialylated bovine colostrum 795:841 degalactosylated/ desialylated bovine colostrum 795:841 We also found that degalactosylated/ desialylated bovine colostrum could significantly enhance the phagocytic activity of mouse peritoneal macrophages in vitro and of intestinal macrophages in vivo. 26168491 7 17 theme Similar 1167:1173 arg1 activator 1281:1289 a potential macrophage activator 1258:1289 a potential macrophage activator for various immunotherapies 1258:1317 CONCLUSION Similar to the use of GcMAF, degalactosylated/desialylated bovine colostrum can be used as a potential macrophage activator for various immunotherapies. 26168491 7 17 theme Similar 1167:1173 arg1 CONCLUSION 1156:1165 CONCLUSION 1156:1165 CONCLUSION Similar to the use of GcMAF, degalactosylated/desialylated bovine colostrum 1156:1241 CONCLUSION Similar to the use of GcMAF, degalactosylated/desialylated bovine colostrum can be used as a potential macrophage activator for various immunotherapies. 26168491 4 18 theme desialylated 687:698 arg1 colostrum 707:715 degalactosylated/ desialylated bovine colostrum 669:715 degalactosylated/ desialylated bovine colostrum 669:715 RESULTS We detected the positive band in degalactosylated/ desialylated bovine colostrum by western blotting using Helix pomatia agglutinin lectin. 26168491 5 19 theme macrophages 915:925 arg1 activity 886:893 the phagocytic activity 871:893 the phagocytic activity of mouse peritoneal macrophages in vitro and of intestinal macrophages 871:964 We also found that degalactosylated/ desialylated bovine colostrum could significantly enhance the phagocytic activity of mouse peritoneal macrophages in vitro and of intestinal macrophages in vivo. 26168491 7 20 theme potential 1260:1268 arg1 activator 1281:1289 a potential macrophage activator 1258:1289 a potential macrophage activator for various immunotherapies 1258:1317 CONCLUSION Similar to the use of GcMAF, degalactosylated/desialylated bovine colostrum can be used as a potential macrophage activator for various immunotherapies. 26168491 7 20 theme potential 1260:1268 arg1 CONCLUSION 1156:1165 CONCLUSION 1156:1165 CONCLUSION Similar to the use of GcMAF, degalactosylated/desialylated bovine colostrum 1156:1241 CONCLUSION Similar to the use of GcMAF, degalactosylated/desialylated bovine colostrum can be used as a potential macrophage activator for various immunotherapies. 26168491 5 21 theme desialylated 813:824 arg1 colostrum 833:841 degalactosylated/ desialylated bovine colostrum 795:841 degalactosylated/ desialylated bovine colostrum 795:841 We also found that degalactosylated/ desialylated bovine colostrum could significantly enhance the phagocytic activity of mouse peritoneal macrophages in vitro and of intestinal macrophages in vivo. 26168491 0 22 theme Bovine 30:35 arg1 Colostrum 37:45 Degalactosylated/Desialylated Bovine Colostrum 0:45 Degalactosylated/Desialylated Bovine Colostrum 0:45 Degalactosylated/Desialylated Bovine Colostrum Induces Macrophage Phagocytic Activity Independently of Inflammatory Cytokine Production. 26168491 0 23 theme Cytokine 116:123 arg1 Production 125:134 Inflammatory Cytokine Production 103:134 Inflammatory Cytokine Production 103:134 Degalactosylated/Desialylated Bovine Colostrum Induces Macrophage Phagocytic Activity Independently of Inflammatory Cytokine Production. 26168491 7 24 theme various 1295:1301 arg1 immunotherapies 1303:1317 various immunotherapies 1295:1317 various immunotherapies 1295:1317 CONCLUSION Similar to the use of GcMAF, degalactosylated/desialylated bovine colostrum can be used as a potential macrophage activator for various immunotherapies. 26168491 2 25 theme factor 489:494 arg1 protein 420:426 the group-specific component (Gc) protein 386:426 the group-specific component (Gc) protein 386:426 In particular, IgA has an O-linked sugar chain similar to that in the group-specific component (Gc) protein, a precursor of the Gc protein-derived macrophage-activating factor (GcMAF). 26168491 2 25 theme factor 489:494 arg1 precursor 431:439 a precursor 429:439 a precursor of the Gc protein-derived macrophage-activating factor (GcMAF) 429:502 In particular, IgA has an O-linked sugar chain similar to that in the group-specific component (Gc) protein, a precursor of the Gc protein-derived macrophage-activating factor (GcMAF). 26168491 4 26 from band 661:664 arg1 colostrum 707:715 degalactosylated/ desialylated bovine colostrum 669:715 degalactosylated/ desialylated bovine colostrum 669:715 RESULTS We detected the positive band in degalactosylated/ desialylated bovine colostrum by western blotting using Helix pomatia agglutinin lectin. 26168491 1 27 theme immunoglobulin 215:228 arg1 IgA 233:235 IgA 233:235 IgA 233:235 BACKGROUND/AIM Colostrum contains antibodies, such as immunoglobulin G (IgG), immunoglobulin A (IgA) and immunoglobulin M (IgM), and, therefore, has potent immunomodulating activity. 26168491 1 27 theme immunoglobulin 215:228 arg1 A 230:230 immunoglobulin A 215:230 immunoglobulin A (IgA) 215:236 BACKGROUND/AIM Colostrum contains antibodies, such as immunoglobulin G (IgG), immunoglobulin A (IgA) and immunoglobulin M (IgM), and, therefore, has potent immunomodulating activity. 26168491 0 28 theme Degalactosylated/Desialylated 0:28 arg1 Colostrum 37:45 Degalactosylated/Desialylated Bovine Colostrum 0:45 Degalactosylated/Desialylated Bovine Colostrum 0:45 Degalactosylated/Desialylated Bovine Colostrum Induces Macrophage Phagocytic Activity Independently of Inflammatory Cytokine Production. 26168491 7 29 theme bovine 1226:1231 arg1 colostrum 1233:1241 degalactosylated/desialylated bovine colostrum 1196:1241 degalactosylated/desialylated bovine colostrum 1196:1241 CONCLUSION Similar to the use of GcMAF, degalactosylated/desialylated bovine colostrum can be used as a potential macrophage activator for various immunotherapies. 26168491 7 29 theme bovine 1226:1231 arg1 GcMAF 1189:1193 GcMAF 1189:1193 GcMAF 1189:1193 CONCLUSION Similar to the use of GcMAF, degalactosylated/desialylated bovine colostrum can be used as a potential macrophage activator for various immunotherapies. 26168491 1 30 theme BACKGROUND/AIM 137:150 arg1 Colostrum 152:160 BACKGROUND/AIM Colostrum 137:160 BACKGROUND/AIM Colostrum 137:160 BACKGROUND/AIM Colostrum contains antibodies, such as immunoglobulin G (IgG), immunoglobulin A (IgA) and immunoglobulin M (IgM), and, therefore, has potent immunomodulating activity. 26168491 2 31 theme similar 367:373 arg1 chain 361:365 an O-linked sugar chain 343:365 an O-linked sugar chain similar to that in the group-specific component (Gc) protein, a precursor of the Gc protein-derived macrophage-activating factor (GcMAF) 343:502 In particular, IgA has an O-linked sugar chain similar to that in the group-specific component (Gc) protein, a precursor of the Gc protein-derived macrophage-activating factor (GcMAF). 26168491 5 32 theme mouse 898:902 arg1 macrophages 915:925 mouse peritoneal macrophages 898:925 mouse peritoneal macrophages 898:925 We also found that degalactosylated/ desialylated bovine colostrum could significantly enhance the phagocytic activity of mouse peritoneal macrophages in vitro and of intestinal macrophages in vivo. 26168491 4 33 theme agglutinin 757:766 arg1 lectin 768:773 Helix pomatia agglutinin lectin 743:773 Helix pomatia agglutinin lectin 743:773 RESULTS We detected the positive band in degalactosylated/ desialylated bovine colostrum by western blotting using Helix pomatia agglutinin lectin. 26168491 3 34 gly degalactosylated/desialylated 580:608 arg1 colostrum 617:625 degalactosylated/desialylated bovine colostrum 580:625 degalactosylated/desialylated bovine colostrum 580:625 In the present study, we investigated the macrophage-activating effects of degalactosylated/desialylated bovine colostrum. 26168491 2 35 theme Gc 416:417 arg1 protein 420:426 the group-specific component (Gc) protein 386:426 the group-specific component (Gc) protein 386:426 In particular, IgA has an O-linked sugar chain similar to that in the group-specific component (Gc) protein, a precursor of the Gc protein-derived macrophage-activating factor (GcMAF). 26168491 2 35 theme Gc 416:417 arg1 precursor 431:439 a precursor 429:439 a precursor of the Gc protein-derived macrophage-activating factor (GcMAF) 429:502 In particular, IgA has an O-linked sugar chain similar to that in the group-specific component (Gc) protein, a precursor of the Gc protein-derived macrophage-activating factor (GcMAF). 26168491 2 36 theme component 405:413 arg1 protein 420:426 the group-specific component (Gc) protein 386:426 the group-specific component (Gc) protein 386:426 In particular, IgA has an O-linked sugar chain similar to that in the group-specific component (Gc) protein, a precursor of the Gc protein-derived macrophage-activating factor (GcMAF). 26168491 2 36 theme component 405:413 arg1 precursor 431:439 a precursor 429:439 a precursor of the Gc protein-derived macrophage-activating factor (GcMAF) 429:502 In particular, IgA has an O-linked sugar chain similar to that in the group-specific component (Gc) protein, a precursor of the Gc protein-derived macrophage-activating factor (GcMAF). 26168491 0 37 theme Phagocytic 66:75 arg1 Activity 77:84 Macrophage Phagocytic Activity 55:84 Macrophage Phagocytic Activity 55:84 Degalactosylated/Desialylated Bovine Colostrum Induces Macrophage Phagocytic Activity Independently of Inflammatory Cytokine Production. 26168491 1 38 theme potent 286:291 arg1 activity 310:317 potent immunomodulating activity 286:317 potent immunomodulating activity 286:317 BACKGROUND/AIM Colostrum contains antibodies, such as immunoglobulin G (IgG), immunoglobulin A (IgA) and immunoglobulin M (IgM), and, therefore, has potent immunomodulating activity. 26168491 4 39 theme positive 652:659 arg1 band 661:664 the positive band 648:664 the positive band in degalactosylated/ desialylated bovine colostrum 648:715 RESULTS We detected the positive band in degalactosylated/ desialylated bovine colostrum by western blotting using Helix pomatia agglutinin lectin. 26168491 0 40 gly Degalactosylated/Desialylated 0:28 arg1 Colostrum 37:45 Degalactosylated/Desialylated Bovine Colostrum 0:45 Degalactosylated/Desialylated Bovine Colostrum 0:45 Degalactosylated/Desialylated Bovine Colostrum Induces Macrophage Phagocytic Activity Independently of Inflammatory Cytokine Production. 26168491 4 41 theme degalactosylated/ 669:685 arg1 colostrum 707:715 degalactosylated/ desialylated bovine colostrum 669:715 degalactosylated/ desialylated bovine colostrum 669:715 RESULTS We detected the positive band in degalactosylated/ desialylated bovine colostrum by western blotting using Helix pomatia agglutinin lectin. 26168491 2 42 theme group-specific 390:403 arg1 protein 420:426 the group-specific component (Gc) protein 386:426 the group-specific component (Gc) protein 386:426 In particular, IgA has an O-linked sugar chain similar to that in the group-specific component (Gc) protein, a precursor of the Gc protein-derived macrophage-activating factor (GcMAF). 26168491 2 42 theme group-specific 390:403 arg1 precursor 431:439 a precursor 429:439 a precursor of the Gc protein-derived macrophage-activating factor (GcMAF) 429:502 In particular, IgA has an O-linked sugar chain similar to that in the group-specific component (Gc) protein, a precursor of the Gc protein-derived macrophage-activating factor (GcMAF). 26168491 0 43 theme Macrophage 55:64 arg1 Activity 77:84 Macrophage Phagocytic Activity 55:84 Macrophage Phagocytic Activity 55:84 Degalactosylated/Desialylated Bovine Colostrum Induces Macrophage Phagocytic Activity Independently of Inflammatory Cytokine Production. 26168491 1 44 theme immunomodulating 293:308 arg1 activity 310:317 potent immunomodulating activity 286:317 potent immunomodulating activity 286:317 BACKGROUND/AIM Colostrum contains antibodies, such as immunoglobulin G (IgG), immunoglobulin A (IgA) and immunoglobulin M (IgM), and, therefore, has potent immunomodulating activity. 26168491 5 45 theme bovine 826:831 arg1 colostrum 833:841 degalactosylated/ desialylated bovine colostrum 795:841 degalactosylated/ desialylated bovine colostrum 795:841 We also found that degalactosylated/ desialylated bovine colostrum could significantly enhance the phagocytic activity of mouse peritoneal macrophages in vitro and of intestinal macrophages in vivo. 26168491 3 46 theme degalactosylated/desialylated 580:608 arg1 colostrum 617:625 degalactosylated/desialylated bovine colostrum 580:625 degalactosylated/desialylated bovine colostrum 580:625 In the present study, we investigated the macrophage-activating effects of degalactosylated/desialylated bovine colostrum. 26168491 2 47 link protein-derived 451:465 arg1 GcMAF 497:501 GcMAF 497:501 GcMAF 497:501 In particular, IgA has an O-linked sugar chain similar to that in the group-specific component (Gc) protein, a precursor of the Gc protein-derived macrophage-activating factor (GcMAF). 26168491 2 47 link protein-derived 451:465 arg1 factor 489:494 Gc protein-derived macrophage-activating factor 448:494 the Gc protein-derived macrophage-activating factor (GcMAF) 444:502 In particular, IgA has an O-linked sugar chain similar to that in the group-specific component (Gc) protein, a precursor of the Gc protein-derived macrophage-activating factor (GcMAF). 26168491 5 48 theme peritoneal 904:913 arg1 macrophages 915:925 mouse peritoneal macrophages 898:925 mouse peritoneal macrophages 898:925 We also found that degalactosylated/ desialylated bovine colostrum could significantly enhance the phagocytic activity of mouse peritoneal macrophages in vitro and of intestinal macrophages in vivo. 26168491 1 49 contain contains 162:169 arg2 antibodies 171:180 antibodies 171:180 antibodies 171:180 BACKGROUND/AIM Colostrum contains antibodies, such as immunoglobulin G (IgG), immunoglobulin A (IgA) and immunoglobulin M (IgM), and, therefore, has potent immunomodulating activity. 26168491 1 49 contain contains 162:169 arg2 G 206:206 immunoglobulin G 191:206 immunoglobulin G (IgG) 191:212 BACKGROUND/AIM Colostrum contains antibodies, such as immunoglobulin G (IgG), immunoglobulin A (IgA) and immunoglobulin M (IgM), and, therefore, has potent immunomodulating activity. 26168491 1 49 contain contains 162:169 arg1 Colostrum 152:160 BACKGROUND/AIM Colostrum 137:160 BACKGROUND/AIM Colostrum 137:160 BACKGROUND/AIM Colostrum contains antibodies, such as immunoglobulin G (IgG), immunoglobulin A (IgA) and immunoglobulin M (IgM), and, therefore, has potent immunomodulating activity. 26168491 1 49 contain contains 162:169 arg2 M 257:257 immunoglobulin M 242:257 immunoglobulin M (IgM) 242:263 BACKGROUND/AIM Colostrum contains antibodies, such as immunoglobulin G (IgG), immunoglobulin A (IgA) and immunoglobulin M (IgM), and, therefore, has potent immunomodulating activity. 26168491 1 49 contain contains 162:169 arg2 A 230:230 immunoglobulin A 215:230 immunoglobulin A (IgA) 215:236 BACKGROUND/AIM Colostrum contains antibodies, such as immunoglobulin G (IgG), immunoglobulin A (IgA) and immunoglobulin M (IgM), and, therefore, has potent immunomodulating activity. 26168491 5 50 theme phagocytic 875:884 arg1 activity 886:893 the phagocytic activity 871:893 the phagocytic activity of mouse peritoneal macrophages in vitro and of intestinal macrophages 871:964 We also found that degalactosylated/ desialylated bovine colostrum could significantly enhance the phagocytic activity of mouse peritoneal macrophages in vitro and of intestinal macrophages in vivo. 26168491 3 51 theme macrophage-activating 547:567 arg1 effects 569:575 the macrophage-activating effects 543:575 the macrophage-activating effects of degalactosylated/desialylated bovine colostrum 543:625 In the present study, we investigated the macrophage-activating effects of degalactosylated/desialylated bovine colostrum. 26168491 7 52 used used 1250:1253 arg2 activator 1281:1289 a potential macrophage activator 1258:1289 a potential macrophage activator for various immunotherapies 1258:1317 CONCLUSION Similar to the use of GcMAF, degalactosylated/desialylated bovine colostrum can be used as a potential macrophage activator for various immunotherapies. 26168491 7 52 used used 1250:1253 arg2 CONCLUSION 1156:1165 CONCLUSION 1156:1165 CONCLUSION Similar to the use of GcMAF, degalactosylated/desialylated bovine colostrum 1156:1241 CONCLUSION Similar to the use of GcMAF, degalactosylated/desialylated bovine colostrum can be used as a potential macrophage activator for various immunotherapies. 26168491 6 53 theme bovine 1014:1019 arg1 colostrum 1021:1029 degalactosylated/desialylated bovine colostrum 984:1029 degalactosylated/desialylated bovine colostrum 984:1029 Besides, degalactosylated/desialylated bovine colostrum did not mediate the production of inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). 26168491 4 54 dep RESULTS 628:634 arg1 detected 639:646 detected 639:646 detected the positive band in degalactosylated/ desialylated bovine colostrum by western blotting using Helix pomatia agglutinin lectin 639:773 RESULTS We detected the positive band in degalactosylated/ desialylated bovine colostrum by western blotting using Helix pomatia agglutinin lectin. 26168491 6 55 theme degalactosylated/desialylated 984:1012 arg1 colostrum 1021:1029 degalactosylated/desialylated bovine colostrum 984:1029 degalactosylated/desialylated bovine colostrum 984:1029 Besides, degalactosylated/desialylated bovine colostrum did not mediate the production of inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). 26168491 7 56 theme degalactosylated/desialylated 1196:1224 arg1 colostrum 1233:1241 degalactosylated/desialylated bovine colostrum 1196:1241 degalactosylated/desialylated bovine colostrum 1196:1241 CONCLUSION Similar to the use of GcMAF, degalactosylated/desialylated bovine colostrum can be used as a potential macrophage activator for various immunotherapies. 26168491 7 56 theme degalactosylated/desialylated 1196:1224 arg1 GcMAF 1189:1193 GcMAF 1189:1193 GcMAF 1189:1193 CONCLUSION Similar to the use of GcMAF, degalactosylated/desialylated bovine colostrum can be used as a potential macrophage activator for various immunotherapies. 26168491 4 57 theme bovine 700:705 arg1 colostrum 707:715 degalactosylated/ desialylated bovine colostrum 669:715 degalactosylated/ desialylated bovine colostrum 669:715 RESULTS We detected the positive band in degalactosylated/ desialylated bovine colostrum by western blotting using Helix pomatia agglutinin lectin. 26168491 4 58 theme pomatia 749:755 arg1 lectin 768:773 Helix pomatia agglutinin lectin 743:773 Helix pomatia agglutinin lectin 743:773 RESULTS We detected the positive band in degalactosylated/ desialylated bovine colostrum by western blotting using Helix pomatia agglutinin lectin. 26168491 1 59 theme immunoglobulin 242:255 arg1 IgM 260:262 IgM 260:262 IgM 260:262 BACKGROUND/AIM Colostrum contains antibodies, such as immunoglobulin G (IgG), immunoglobulin A (IgA) and immunoglobulin M (IgM), and, therefore, has potent immunomodulating activity. 26168491 1 59 theme immunoglobulin 242:255 arg1 M 257:257 immunoglobulin M 242:257 immunoglobulin M (IgM) 242:263 BACKGROUND/AIM Colostrum contains antibodies, such as immunoglobulin G (IgG), immunoglobulin A (IgA) and immunoglobulin M (IgM), and, therefore, has potent immunomodulating activity. 26168491 5 60 gly desialylated 813:824 arg1 colostrum 833:841 degalactosylated/ desialylated bovine colostrum 795:841 degalactosylated/ desialylated bovine colostrum 795:841 We also found that degalactosylated/ desialylated bovine colostrum could significantly enhance the phagocytic activity of mouse peritoneal macrophages in vitro and of intestinal macrophages in vivo. 26168491 4 61 theme Helix 743:747 arg1 lectin 768:773 Helix pomatia agglutinin lectin 743:773 Helix pomatia agglutinin lectin 743:773 RESULTS We detected the positive band in degalactosylated/ desialylated bovine colostrum by western blotting using Helix pomatia agglutinin lectin. 26168491 6 62 theme necrosis 1102:1109 arg1 TNF-α 1121:1125 TNF-α 1121:1125 TNF-α 1121:1125 Besides, degalactosylated/desialylated bovine colostrum did not mediate the production of inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). 26168491 6 62 theme necrosis 1102:1109 arg1 factor-α 1111:1118 tumor necrosis factor-α 1096:1118 tumor necrosis factor-α (TNF-α) 1096:1126 Besides, degalactosylated/desialylated bovine colostrum did not mediate the production of inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). 26168491 0 63 theme Inflammatory 103:114 arg1 Production 125:134 Inflammatory Cytokine Production 103:134 Inflammatory Cytokine Production 103:134 Degalactosylated/Desialylated Bovine Colostrum Induces Macrophage Phagocytic Activity Independently of Inflammatory Cytokine Production. 26168491 5 64 theme intestinal 943:952 arg1 macrophages 954:964 intestinal macrophages 943:964 intestinal macrophages 943:964 We also found that degalactosylated/ desialylated bovine colostrum could significantly enhance the phagocytic activity of mouse peritoneal macrophages in vitro and of intestinal macrophages in vivo. 26168491 3 65 theme bovine 610:615 arg1 colostrum 617:625 degalactosylated/desialylated bovine colostrum 580:625 degalactosylated/desialylated bovine colostrum 580:625 In the present study, we investigated the macrophage-activating effects of degalactosylated/desialylated bovine colostrum. 26168491 1 66 theme immunoglobulin 191:204 arg1 G 206:206 immunoglobulin G 191:206 immunoglobulin G (IgG) 191:212 BACKGROUND/AIM Colostrum contains antibodies, such as immunoglobulin G (IgG), immunoglobulin A (IgA) and immunoglobulin M (IgM), and, therefore, has potent immunomodulating activity. 26168491 1 66 theme immunoglobulin 191:204 arg1 IgG 209:211 IgG 209:211 IgG 209:211 BACKGROUND/AIM Colostrum contains antibodies, such as immunoglobulin G (IgG), immunoglobulin A (IgA) and immunoglobulin M (IgM), and, therefore, has potent immunomodulating activity. 26168491 6 67 theme tumor 1096:1100 arg1 TNF-α 1121:1125 TNF-α 1121:1125 TNF-α 1121:1125 Besides, degalactosylated/desialylated bovine colostrum did not mediate the production of inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). 26168491 6 67 theme tumor 1096:1100 arg1 factor-α 1111:1118 tumor necrosis factor-α 1096:1118 tumor necrosis factor-α (TNF-α) 1096:1126 Besides, degalactosylated/desialylated bovine colostrum did not mediate the production of inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). 26168491 2 68 theme macrophage-activating 467:487 arg1 GcMAF 497:501 GcMAF 497:501 GcMAF 497:501 In particular, IgA has an O-linked sugar chain similar to that in the group-specific component (Gc) protein, a precursor of the Gc protein-derived macrophage-activating factor (GcMAF). 26168491 2 68 theme macrophage-activating 467:487 arg1 factor 489:494 Gc protein-derived macrophage-activating factor 448:494 the Gc protein-derived macrophage-activating factor (GcMAF) 444:502 In particular, IgA has an O-linked sugar chain similar to that in the group-specific component (Gc) protein, a precursor of the Gc protein-derived macrophage-activating factor (GcMAF). 26168491 3 69 theme colostrum 617:625 arg1 effects 569:575 the macrophage-activating effects 543:575 the macrophage-activating effects of degalactosylated/desialylated bovine colostrum 543:625 In the present study, we investigated the macrophage-activating effects of degalactosylated/desialylated bovine colostrum. 26168491 2 70 theme sugar 355:359 arg1 chain 361:365 an O-linked sugar chain 343:365 an O-linked sugar chain similar to that in the group-specific component (Gc) protein, a precursor of the Gc protein-derived macrophage-activating factor (GcMAF) 343:502 In particular, IgA has an O-linked sugar chain similar to that in the group-specific component (Gc) protein, a precursor of the Gc protein-derived macrophage-activating factor (GcMAF). 25520704 7 0 from alterations 1037:1047 arg1 levels 1061:1066 O-GlcNAc levels 1052:1066 O-GlcNAc levels 1052:1066 We reason that alterations in O-GlcNAc levels affect OGA and OGT transcription. 25520704 10 1 theme Polymerase 1696:1705 arg1 immunoprecipitation 1720:1738 RNA Polymerase II chromatin immunoprecipitation 1692:1738 RNA Polymerase II chromatin immunoprecipitation 1692:1738 Pretreating cells with protein translation inhibitor cycloheximide did not stabilize OGT or OGA protein expression in the presence of TMG; nor did TMG stabilize OGT and OGA mRNA levels when cells were treated with RNA transcription inhibitor actinomycin D. Finally, we performed RNA Polymerase II chromatin immunoprecipitation at the OGA promoter and found that RNA Pol II occupancy at the transcription start site was lower after prolonged TMG treatment. 25520704 1 2 attach attachment 162:171 arg1 threonine 227:235 threonine 227:235 threonine 227:235 O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification involving an attachment of a single β-N-acetylglucosamine moiety to serine or threonine residues in nuclear and cytoplasmic proteins. 25520704 1 2 attach attachment 162:171 arg1 serine 217:222 serine 217:222 serine 217:222 O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification involving an attachment of a single β-N-acetylglucosamine moiety to serine or threonine residues in nuclear and cytoplasmic proteins. 25520704 1 2 attach attachment 162:171 arg2 moiety 207:212 a single β-N-acetylglucosamine moiety 176:212 a single β-N-acetylglucosamine moiety 176:212 O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification involving an attachment of a single β-N-acetylglucosamine moiety to serine or threonine residues in nuclear and cytoplasmic proteins. 25520704 10 3 theme OGA 1747:1749 arg1 promoter 1751:1758 the OGA promoter 1743:1758 the OGA promoter 1743:1758 Pretreating cells with protein translation inhibitor cycloheximide did not stabilize OGT or OGA protein expression in the presence of TMG; nor did TMG stabilize OGT and OGA mRNA levels when cells were treated with RNA transcription inhibitor actinomycin D. Finally, we performed RNA Polymerase II chromatin immunoprecipitation at the OGA promoter and found that RNA Pol II occupancy at the transcription start site was lower after prolonged TMG treatment. 25520704 4 4 theme many 715:718 arg1 transcription 796:808 gene transcription 791:808 gene transcription 791:808 This process termed O-GlcNAc homeostasis appears to be critical to the regulation of many cellular functions including cell cycle progress, stress response, and gene transcription. 25520704 4 4 theme many 715:718 arg1 progress 760:767 cell cycle progress 749:767 cell cycle progress 749:767 This process termed O-GlcNAc homeostasis appears to be critical to the regulation of many cellular functions including cell cycle progress, stress response, and gene transcription. 25520704 4 4 theme many 715:718 arg1 response 777:784 stress response 770:784 stress response 770:784 This process termed O-GlcNAc homeostasis appears to be critical to the regulation of many cellular functions including cell cycle progress, stress response, and gene transcription. 25520704 4 4 theme many 715:718 arg1 functions 729:737 many cellular functions 715:737 many cellular functions including cell cycle progress, stress response, and gene transcription 715:808 This process termed O-GlcNAc homeostasis appears to be critical to the regulation of many cellular functions including cell cycle progress, stress response, and gene transcription. 25520704 7 5 theme OGT 1083:1085 arg1 transcription 1087:1099 OGA and OGT transcription 1075:1099 OGA and OGT transcription 1075:1099 We reason that alterations in O-GlcNAc levels affect OGA and OGT transcription. 25520704 10 6 theme Pretreating 1413:1423 arg1 cells 1425:1429 Pretreating cells 1413:1429 Pretreating cells with protein translation inhibitor cycloheximide 1413:1478 Pretreating cells with protein translation inhibitor cycloheximide did not stabilize OGT or OGA protein expression in the presence of TMG; nor did TMG stabilize OGT and OGA mRNA levels when cells were treated with RNA transcription inhibitor actinomycin D. Finally, we performed RNA Polymerase II chromatin immunoprecipitation at the OGA promoter and found that RNA Pol II occupancy at the transcription start site was lower after prolonged TMG treatment. 25520704 1 7 theme β-N-acetylglucosamine 185:205 arg1 moiety 207:212 a single β-N-acetylglucosamine moiety 176:212 a single β-N-acetylglucosamine moiety 176:212 O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification involving an attachment of a single β-N-acetylglucosamine moiety to serine or threonine residues in nuclear and cytoplasmic proteins. 25520704 10 8 theme OGA 1582:1584 arg1 levels 1591:1596 OGA mRNA levels 1582:1596 OGA mRNA levels 1582:1596 Pretreating cells with protein translation inhibitor cycloheximide did not stabilize OGT or OGA protein expression in the presence of TMG; nor did TMG stabilize OGT and OGA mRNA levels when cells were treated with RNA transcription inhibitor actinomycin D. Finally, we performed RNA Polymerase II chromatin immunoprecipitation at the OGA promoter and found that RNA Pol II occupancy at the transcription start site was lower after prolonged TMG treatment. 25520704 7 9 theme OGA 1075:1077 arg1 transcription 1087:1099 OGA and OGT transcription 1075:1099 OGA and OGT transcription 1075:1099 We reason that alterations in O-GlcNAc levels affect OGA and OGT transcription. 25520704 3 10 theme baseline 583:590 arg1 level 592:596 a baseline level 581:596 a baseline level 581:596 The levels of O-GlcNAc can rapidly change in response to fluctuations in the extracellular environment; however, O-GlcNAcylation returns to a baseline level quickly after stimulus removal. 25520704 8 11 theme OGT 1236:1238 arg1 expression 1248:1257 decreased OGT protein expression 1226:1257 decreased OGT protein expression 1226:1257 We treated several human cell lines with Thiamet-G (TMG, an OGA inhibitor) to increase overall O-GlcNAc levels resulting in decreased OGT protein expression and increased OGA protein expression. 25520704 4 12 theme O-GlcNAc 650:657 arg1 homeostasis 659:669 O-GlcNAc homeostasis 650:669 O-GlcNAc homeostasis 650:669 This process termed O-GlcNAc homeostasis appears to be critical to the regulation of many cellular functions including cell cycle progress, stress response, and gene transcription. 25520704 1 13 from threonine 227:235 arg1 proteins 273:280 nuclear and cytoplasmic proteins 249:280 nuclear and cytoplasmic proteins 249:280 O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification involving an attachment of a single β-N-acetylglucosamine moiety to serine or threonine residues in nuclear and cytoplasmic proteins. 25520704 8 14 theme overall 1189:1195 arg1 levels 1206:1211 overall O-GlcNAc levels 1189:1211 overall O-GlcNAc levels 1189:1211 We treated several human cell lines with Thiamet-G (TMG, an OGA inhibitor) to increase overall O-GlcNAc levels resulting in decreased OGT protein expression and increased OGA protein expression. 25520704 8 15 theme increased 1263:1271 arg1 expression 1285:1294 increased OGA protein expression 1263:1294 increased OGA protein expression 1263:1294 We treated several human cell lines with Thiamet-G (TMG, an OGA inhibitor) to increase overall O-GlcNAc levels resulting in decreased OGT protein expression and increased OGA protein expression. 25520704 10 16 theme Pol 1779:1781 arg1 occupancy 1786:1794 RNA Pol II occupancy 1775:1794 RNA Pol II occupancy at the transcription start site 1775:1826 Pretreating cells with protein translation inhibitor cycloheximide did not stabilize OGT or OGA protein expression in the presence of TMG; nor did TMG stabilize OGT and OGA mRNA levels when cells were treated with RNA transcription inhibitor actinomycin D. Finally, we performed RNA Polymerase II chromatin immunoprecipitation at the OGA promoter and found that RNA Pol II occupancy at the transcription start site was lower after prolonged TMG treatment. 25520704 1 17 from serine 217:222 arg1 proteins 273:280 nuclear and cytoplasmic proteins 249:280 nuclear and cytoplasmic proteins 249:280 O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification involving an attachment of a single β-N-acetylglucosamine moiety to serine or threonine residues in nuclear and cytoplasmic proteins. 25520704 1 18 theme post-translational 117:134 arg1 modification 136:147 a post-translational modification 115:147 a post-translational modification involving an attachment of a single β-N-acetylglucosamine moiety to serine or threonine residues in nuclear and cytoplasmic proteins 115:280 O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification involving an attachment of a single β-N-acetylglucosamine moiety to serine or threonine residues in nuclear and cytoplasmic proteins. 25520704 1 18 theme post-translational 117:134 arg1 N-acetylglucosamine 81:99 O-linked N-acetylglucosamine 72:99 O-linked N-acetylglucosamine (O-GlcNAc) 72:110 O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification involving an attachment of a single β-N-acetylglucosamine moiety to serine or threonine residues in nuclear and cytoplasmic proteins. 25520704 8 19 theme protein 1277:1283 arg1 expression 1285:1294 increased OGA protein expression 1263:1294 increased OGA protein expression 1263:1294 We treated several human cell lines with Thiamet-G (TMG, an OGA inhibitor) to increase overall O-GlcNAc levels resulting in decreased OGT protein expression and increased OGA protein expression. 25520704 10 20 theme start 1817:1821 arg1 site 1823:1826 the transcription start site 1799:1826 the transcription start site 1799:1826 Pretreating cells with protein translation inhibitor cycloheximide did not stabilize OGT or OGA protein expression in the presence of TMG; nor did TMG stabilize OGT and OGA mRNA levels when cells were treated with RNA transcription inhibitor actinomycin D. Finally, we performed RNA Polymerase II chromatin immunoprecipitation at the OGA promoter and found that RNA Pol II occupancy at the transcription start site was lower after prolonged TMG treatment. 25520704 4 21 theme functions 729:737 arg1 regulation 701:710 the regulation 697:710 the regulation of many cellular functions including cell cycle progress, stress response, and gene transcription 697:808 This process termed O-GlcNAc homeostasis appears to be critical to the regulation of many cellular functions including cell cycle progress, stress response, and gene transcription. 25520704 3 22 theme stimulus 612:619 arg1 removal 621:627 stimulus removal 612:627 stimulus removal 612:627 The levels of O-GlcNAc can rapidly change in response to fluctuations in the extracellular environment; however, O-GlcNAcylation returns to a baseline level quickly after stimulus removal. 25520704 10 23 theme translation 1444:1454 arg1 cycloheximide 1466:1478 protein translation inhibitor cycloheximide 1436:1478 protein translation inhibitor cycloheximide 1436:1478 Pretreating cells with protein translation inhibitor cycloheximide did not stabilize OGT or OGA protein expression in the presence of TMG; nor did TMG stabilize OGT and OGA mRNA levels when cells were treated with RNA transcription inhibitor actinomycin D. Finally, we performed RNA Polymerase II chromatin immunoprecipitation at the OGA promoter and found that RNA Pol II occupancy at the transcription start site was lower after prolonged TMG treatment. 25520704 2 24 theme Cellular 283:290 arg1 levels 301:306 Cellular O-GlcNAc levels 283:306 Cellular O-GlcNAc levels 283:306 Cellular O-GlcNAc levels are regulated by two enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), which add and remove the modification, respectively. 25520704 8 25 dep Thiamet-G 1143:1151 arg1 inhibitor 1166:1174 an OGA inhibitor 1159:1174 an OGA inhibitor 1159:1174 We treated several human cell lines with Thiamet-G (TMG, an OGA inhibitor) to increase overall O-GlcNAc levels resulting in decreased OGT protein expression and increased OGA protein expression. 25520704 8 25 dep Thiamet-G 1143:1151 arg1 TMG 1154:1156 TMG 1154:1156 TMG 1154:1156 We treated several human cell lines with Thiamet-G (TMG, an OGA inhibitor) to increase overall O-GlcNAc levels resulting in decreased OGT protein expression and increased OGA protein expression. 25520704 4 26 theme stress 770:775 arg1 response 777:784 stress response 770:784 stress response 770:784 This process termed O-GlcNAc homeostasis appears to be critical to the regulation of many cellular functions including cell cycle progress, stress response, and gene transcription. 25520704 4 27 theme cellular 720:727 arg1 transcription 796:808 gene transcription 791:808 gene transcription 791:808 This process termed O-GlcNAc homeostasis appears to be critical to the regulation of many cellular functions including cell cycle progress, stress response, and gene transcription. 25520704 4 27 theme cellular 720:727 arg1 progress 760:767 cell cycle progress 749:767 cell cycle progress 749:767 This process termed O-GlcNAc homeostasis appears to be critical to the regulation of many cellular functions including cell cycle progress, stress response, and gene transcription. 25520704 4 27 theme cellular 720:727 arg1 response 777:784 stress response 770:784 stress response 770:784 This process termed O-GlcNAc homeostasis appears to be critical to the regulation of many cellular functions including cell cycle progress, stress response, and gene transcription. 25520704 4 27 theme cellular 720:727 arg1 functions 729:737 many cellular functions 715:737 many cellular functions including cell cycle progress, stress response, and gene transcription 715:808 This process termed O-GlcNAc homeostasis appears to be critical to the regulation of many cellular functions including cell cycle progress, stress response, and gene transcription. 25520704 5 28 from Disruptions 811:821 arg1 homeostasis 835:845 O-GlcNAc homeostasis 826:845 O-GlcNAc homeostasis 826:845 Disruptions in O-GlcNAc homeostasis are proposed to lead to the development of diseases, such as cancer, diabetes, and Alzheimer's disease. 25520704 4 29 theme cell 749:752 arg1 progress 760:767 cell cycle progress 749:767 cell cycle progress 749:767 This process termed O-GlcNAc homeostasis appears to be critical to the regulation of many cellular functions including cell cycle progress, stress response, and gene transcription. 25520704 0 30 theme O-GlcNAcase 0:10 arg1 Expression 12:21 O-GlcNAcase Expression 0:21 O-GlcNAcase Expression 0:21 O-GlcNAcase Expression is Sensitive to Changes in O-GlcNAc Homeostasis. 25520704 3 31 dep fluctuations 498:509 arg1 response 486:493 response 486:493 response 486:493 The levels of O-GlcNAc can rapidly change in response to fluctuations in the extracellular environment; however, O-GlcNAcylation returns to a baseline level quickly after stimulus removal. 25520704 11 32 theme O-GlcNAc 1949:1956 arg1 homeostasis 1958:1968 O-GlcNAc homeostasis 1949:1968 O-GlcNAc homeostasis 1949:1968 Together, these data suggest that OGA transcription was sensitive to changes in O-GlcNAc homeostasis and was potentially regulated by O-GlcNAc. 25520704 10 33 theme OGA 1505:1507 arg1 expression 1517:1526 OGA protein expression 1505:1526 OGA protein expression 1505:1526 Pretreating cells with protein translation inhibitor cycloheximide did not stabilize OGT or OGA protein expression in the presence of TMG; nor did TMG stabilize OGT and OGA mRNA levels when cells were treated with RNA transcription inhibitor actinomycin D. Finally, we performed RNA Polymerase II chromatin immunoprecipitation at the OGA promoter and found that RNA Pol II occupancy at the transcription start site was lower after prolonged TMG treatment. 25520704 3 34 theme O-GlcNAc 455:462 arg1 levels 445:450 The levels 441:450 The levels of O-GlcNAc 441:462 The levels of O-GlcNAc can rapidly change in response to fluctuations in the extracellular environment; however, O-GlcNAcylation returns to a baseline level quickly after stimulus removal. 25520704 10 35 from site 1823:1826 arg1 occupancy 1786:1794 RNA Pol II occupancy 1775:1794 RNA Pol II occupancy at the transcription start site 1775:1826 Pretreating cells with protein translation inhibitor cycloheximide did not stabilize OGT or OGA protein expression in the presence of TMG; nor did TMG stabilize OGT and OGA mRNA levels when cells were treated with RNA transcription inhibitor actinomycin D. Finally, we performed RNA Polymerase II chromatin immunoprecipitation at the OGA promoter and found that RNA Pol II occupancy at the transcription start site was lower after prolonged TMG treatment. 25520704 9 36 theme TMG 1342:1344 arg1 treatment 1346:1354 TMG treatment 1342:1354 TMG treatment 1342:1354 OGT transcript levels slightly declined with TMG treatment, but OGA transcript levels were significantly increased. 25520704 10 37 theme RNA 1692:1694 arg1 Polymerase 1696:1705 RNA Polymerase II 1692:1708 RNA Polymerase II chromatin immunoprecipitation 1692:1738 Pretreating cells with protein translation inhibitor cycloheximide did not stabilize OGT or OGA protein expression in the presence of TMG; nor did TMG stabilize OGT and OGA mRNA levels when cells were treated with RNA transcription inhibitor actinomycin D. Finally, we performed RNA Polymerase II chromatin immunoprecipitation at the OGA promoter and found that RNA Pol II occupancy at the transcription start site was lower after prolonged TMG treatment. 25520704 4 38 theme gene 791:794 arg1 transcription 796:808 gene transcription 791:808 gene transcription 791:808 This process termed O-GlcNAc homeostasis appears to be critical to the regulation of many cellular functions including cell cycle progress, stress response, and gene transcription. 25520704 9 39 theme OGA 1361:1363 arg1 levels 1376:1381 OGA transcript levels 1361:1381 OGA transcript levels 1361:1381 OGT transcript levels slightly declined with TMG treatment, but OGA transcript levels were significantly increased. 25520704 10 40 theme TMG 1854:1856 arg1 treatment 1858:1866 prolonged TMG treatment 1844:1866 prolonged TMG treatment 1844:1866 Pretreating cells with protein translation inhibitor cycloheximide did not stabilize OGT or OGA protein expression in the presence of TMG; nor did TMG stabilize OGT and OGA mRNA levels when cells were treated with RNA transcription inhibitor actinomycin D. Finally, we performed RNA Polymerase II chromatin immunoprecipitation at the OGA promoter and found that RNA Pol II occupancy at the transcription start site was lower after prolonged TMG treatment. 25520704 2 41 dep enzymes 329:335 arg1 OGT 360:362 OGT 360:362 OGT 360:362 Cellular O-GlcNAc levels are regulated by two enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), which add and remove the modification, respectively. 25520704 2 41 dep enzymes 329:335 arg1 O-GlcNAcase 369:379 O-GlcNAcase 369:379 O-GlcNAcase (OGA) 369:385 Cellular O-GlcNAc levels are regulated by two enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), which add and remove the modification, respectively. 25520704 2 41 dep enzymes 329:335 arg1 transferase 347:357 O-GlcNAc transferase 338:357 O-GlcNAc transferase (OGT) 338:363 Cellular O-GlcNAc levels are regulated by two enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), which add and remove the modification, respectively. 25520704 2 41 dep enzymes 329:335 arg1 enzymes 329:335 two enzymes 325:335 two enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) 325:385 Cellular O-GlcNAc levels are regulated by two enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), which add and remove the modification, respectively. 25520704 2 41 dep enzymes 329:335 arg1 OGA 382:384 OGA 382:384 OGA 382:384 Cellular O-GlcNAc levels are regulated by two enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), which add and remove the modification, respectively. 25520704 8 42 theme several 1113:1119 arg1 lines 1132:1136 several human cell lines 1113:1136 several human cell lines with Thiamet-G (TMG, an OGA inhibitor) 1113:1175 We treated several human cell lines with Thiamet-G (TMG, an OGA inhibitor) to increase overall O-GlcNAc levels resulting in decreased OGT protein expression and increased OGA protein expression. 25520704 8 43 theme cell 1127:1130 arg1 lines 1132:1136 several human cell lines 1113:1136 several human cell lines with Thiamet-G (TMG, an OGA inhibitor) 1113:1175 We treated several human cell lines with Thiamet-G (TMG, an OGA inhibitor) to increase overall O-GlcNAc levels resulting in decreased OGT protein expression and increased OGA protein expression. 25520704 1 44 link O-linked 72:79 arg1 modification 136:147 a post-translational modification 115:147 a post-translational modification involving an attachment of a single β-N-acetylglucosamine moiety to serine or threonine residues in nuclear and cytoplasmic proteins 115:280 O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification involving an attachment of a single β-N-acetylglucosamine moiety to serine or threonine residues in nuclear and cytoplasmic proteins. 25520704 1 44 link O-linked 72:79 arg1 O-GlcNAc 102:109 O-GlcNAc 102:109 O-GlcNAc 102:109 O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification involving an attachment of a single β-N-acetylglucosamine moiety to serine or threonine residues in nuclear and cytoplasmic proteins. 25520704 1 44 link O-linked 72:79 arg1 N-acetylglucosamine 81:99 O-linked N-acetylglucosamine 72:99 O-linked N-acetylglucosamine (O-GlcNAc) 72:110 O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification involving an attachment of a single β-N-acetylglucosamine moiety to serine or threonine residues in nuclear and cytoplasmic proteins. 25520704 3 45 from fluctuations 498:509 arg1 environment 532:542 the extracellular environment 514:542 the extracellular environment 514:542 The levels of O-GlcNAc can rapidly change in response to fluctuations in the extracellular environment; however, O-GlcNAcylation returns to a baseline level quickly after stimulus removal. 25520704 2 46 theme O-GlcNAc 338:345 arg1 OGT 360:362 OGT 360:362 OGT 360:362 Cellular O-GlcNAc levels are regulated by two enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), which add and remove the modification, respectively. 25520704 2 46 theme O-GlcNAc 338:345 arg1 enzymes 329:335 two enzymes 325:335 two enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) 325:385 Cellular O-GlcNAc levels are regulated by two enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), which add and remove the modification, respectively. 25520704 2 46 theme O-GlcNAc 338:345 arg1 transferase 347:357 O-GlcNAc transferase 338:357 O-GlcNAc transferase (OGT) 338:363 Cellular O-GlcNAc levels are regulated by two enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), which add and remove the modification, respectively. 25520704 3 47 theme extracellular 518:530 arg1 environment 532:542 the extracellular environment 514:542 the extracellular environment 514:542 The levels of O-GlcNAc can rapidly change in response to fluctuations in the extracellular environment; however, O-GlcNAcylation returns to a baseline level quickly after stimulus removal. 25520704 1 48 theme single 178:183 arg1 moiety 207:212 a single β-N-acetylglucosamine moiety 176:212 a single β-N-acetylglucosamine moiety 176:212 O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification involving an attachment of a single β-N-acetylglucosamine moiety to serine or threonine residues in nuclear and cytoplasmic proteins. 25520704 8 49 theme O-GlcNAc 1197:1204 arg1 levels 1206:1211 overall O-GlcNAc levels 1189:1211 overall O-GlcNAc levels 1189:1211 We treated several human cell lines with Thiamet-G (TMG, an OGA inhibitor) to increase overall O-GlcNAc levels resulting in decreased OGT protein expression and increased OGA protein expression. 25520704 10 50 theme mRNA 1586:1589 arg1 levels 1591:1596 OGA mRNA levels 1582:1596 OGA mRNA levels 1582:1596 Pretreating cells with protein translation inhibitor cycloheximide did not stabilize OGT or OGA protein expression in the presence of TMG; nor did TMG stabilize OGT and OGA mRNA levels when cells were treated with RNA transcription inhibitor actinomycin D. Finally, we performed RNA Polymerase II chromatin immunoprecipitation at the OGA promoter and found that RNA Pol II occupancy at the transcription start site was lower after prolonged TMG treatment. 25520704 10 51 theme RNA 1775:1777 arg1 Pol 1779:1781 RNA Pol II 1775:1784 RNA Pol II occupancy at the transcription start site 1775:1826 Pretreating cells with protein translation inhibitor cycloheximide did not stabilize OGT or OGA protein expression in the presence of TMG; nor did TMG stabilize OGT and OGA mRNA levels when cells were treated with RNA transcription inhibitor actinomycin D. Finally, we performed RNA Polymerase II chromatin immunoprecipitation at the OGA promoter and found that RNA Pol II occupancy at the transcription start site was lower after prolonged TMG treatment. 25520704 1 52 theme moiety 207:212 arg1 attachment 162:171 an attachment 159:171 an attachment of a single β-N-acetylglucosamine moiety to serine or threonine residues in nuclear and cytoplasmic proteins 159:280 O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification involving an attachment of a single β-N-acetylglucosamine moiety to serine or threonine residues in nuclear and cytoplasmic proteins. 25520704 7 53 theme O-GlcNAc 1052:1059 arg1 levels 1061:1066 O-GlcNAc levels 1052:1066 O-GlcNAc levels 1052:1066 We reason that alterations in O-GlcNAc levels affect OGA and OGT transcription. 25520704 8 54 theme OGA 1162:1164 arg1 inhibitor 1166:1174 an OGA inhibitor 1159:1174 an OGA inhibitor 1159:1174 We treated several human cell lines with Thiamet-G (TMG, an OGA inhibitor) to increase overall O-GlcNAc levels resulting in decreased OGT protein expression and increased OGA protein expression. 25520704 8 54 theme OGA 1162:1164 arg1 TMG 1154:1156 TMG 1154:1156 TMG 1154:1156 We treated several human cell lines with Thiamet-G (TMG, an OGA inhibitor) to increase overall O-GlcNAc levels resulting in decreased OGT protein expression and increased OGA protein expression. 25520704 6 55 theme O-GlcNAc 951:958 arg1 homeostasis 960:970 O-GlcNAc homeostasis 951:970 O-GlcNAc homeostasis 951:970 O-GlcNAc homeostasis is correlated with the expression of OGT and OGA. 25520704 11 56 from changes 1938:1944 arg1 homeostasis 1958:1968 O-GlcNAc homeostasis 1949:1968 O-GlcNAc homeostasis 1949:1968 Together, these data suggest that OGA transcription was sensitive to changes in O-GlcNAc homeostasis and was potentially regulated by O-GlcNAc. 25520704 8 57 theme decreased 1226:1234 arg1 expression 1248:1257 decreased OGT protein expression 1226:1257 decreased OGT protein expression 1226:1257 We treated several human cell lines with Thiamet-G (TMG, an OGA inhibitor) to increase overall O-GlcNAc levels resulting in decreased OGT protein expression and increased OGA protein expression. 25520704 8 58 theme protein 1240:1246 arg1 expression 1248:1257 decreased OGT protein expression 1226:1257 decreased OGT protein expression 1226:1257 We treated several human cell lines with Thiamet-G (TMG, an OGA inhibitor) to increase overall O-GlcNAc levels resulting in decreased OGT protein expression and increased OGA protein expression. 25520704 2 59 theme O-GlcNAc 292:299 arg1 levels 301:306 Cellular O-GlcNAc levels 283:306 Cellular O-GlcNAc levels 283:306 Cellular O-GlcNAc levels are regulated by two enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), which add and remove the modification, respectively. 25520704 6 60 theme OGA 1017:1019 arg1 expression 995:1004 the expression 991:1004 the expression of OGT and OGA 991:1019 O-GlcNAc homeostasis is correlated with the expression of OGT and OGA. 25520704 8 61 theme OGA 1273:1275 arg1 expression 1285:1294 increased OGA protein expression 1263:1294 increased OGA protein expression 1263:1294 We treated several human cell lines with Thiamet-G (TMG, an OGA inhibitor) to increase overall O-GlcNAc levels resulting in decreased OGT protein expression and increased OGA protein expression. 25520704 10 62 theme transcription 1803:1815 arg1 site 1823:1826 the transcription start site 1799:1826 the transcription start site 1799:1826 Pretreating cells with protein translation inhibitor cycloheximide did not stabilize OGT or OGA protein expression in the presence of TMG; nor did TMG stabilize OGT and OGA mRNA levels when cells were treated with RNA transcription inhibitor actinomycin D. Finally, we performed RNA Polymerase II chromatin immunoprecipitation at the OGA promoter and found that RNA Pol II occupancy at the transcription start site was lower after prolonged TMG treatment. 25520704 5 63 theme diseases 890:897 arg1 development 875:885 the development 871:885 the development of diseases, such as cancer, diabetes, and Alzheimer's disease 871:948 Disruptions in O-GlcNAc homeostasis are proposed to lead to the development of diseases, such as cancer, diabetes, and Alzheimer's disease. 25520704 6 64 theme OGT 1009:1011 arg1 expression 995:1004 the expression 991:1004 the expression of OGT and OGA 991:1019 O-GlcNAc homeostasis is correlated with the expression of OGT and OGA. 25520704 10 65 theme protein 1436:1442 arg1 cycloheximide 1466:1478 protein translation inhibitor cycloheximide 1436:1478 protein translation inhibitor cycloheximide 1436:1478 Pretreating cells with protein translation inhibitor cycloheximide did not stabilize OGT or OGA protein expression in the presence of TMG; nor did TMG stabilize OGT and OGA mRNA levels when cells were treated with RNA transcription inhibitor actinomycin D. Finally, we performed RNA Polymerase II chromatin immunoprecipitation at the OGA promoter and found that RNA Pol II occupancy at the transcription start site was lower after prolonged TMG treatment. 25520704 8 66 with lines 1132:1136 arg1 Thiamet-G 1143:1151 Thiamet-G 1143:1151 Thiamet-G (TMG, an OGA inhibitor) 1143:1175 We treated several human cell lines with Thiamet-G (TMG, an OGA inhibitor) to increase overall O-GlcNAc levels resulting in decreased OGT protein expression and increased OGA protein expression. 25520704 1 67 theme O-linked 72:79 arg1 modification 136:147 a post-translational modification 115:147 a post-translational modification involving an attachment of a single β-N-acetylglucosamine moiety to serine or threonine residues in nuclear and cytoplasmic proteins 115:280 O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification involving an attachment of a single β-N-acetylglucosamine moiety to serine or threonine residues in nuclear and cytoplasmic proteins. 25520704 1 67 theme O-linked 72:79 arg1 O-GlcNAc 102:109 O-GlcNAc 102:109 O-GlcNAc 102:109 O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification involving an attachment of a single β-N-acetylglucosamine moiety to serine or threonine residues in nuclear and cytoplasmic proteins. 25520704 1 67 theme O-linked 72:79 arg1 N-acetylglucosamine 81:99 O-linked N-acetylglucosamine 72:99 O-linked N-acetylglucosamine (O-GlcNAc) 72:110 O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification involving an attachment of a single β-N-acetylglucosamine moiety to serine or threonine residues in nuclear and cytoplasmic proteins. 25520704 10 68 with cells 1425:1429 arg1 cycloheximide 1466:1478 protein translation inhibitor cycloheximide 1436:1478 protein translation inhibitor cycloheximide 1436:1478 Pretreating cells with protein translation inhibitor cycloheximide did not stabilize OGT or OGA protein expression in the presence of TMG; nor did TMG stabilize OGT and OGA mRNA levels when cells were treated with RNA transcription inhibitor actinomycin D. Finally, we performed RNA Polymerase II chromatin immunoprecipitation at the OGA promoter and found that RNA Pol II occupancy at the transcription start site was lower after prolonged TMG treatment. 25520704 0 69 from Changes 39:45 arg1 Homeostasis 59:69 O-GlcNAc Homeostasis 50:69 O-GlcNAc Homeostasis 50:69 O-GlcNAcase Expression is Sensitive to Changes in O-GlcNAc Homeostasis. 25520704 1 70 theme nuclear 249:255 arg1 proteins 273:280 nuclear and cytoplasmic proteins 249:280 nuclear and cytoplasmic proteins 249:280 O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification involving an attachment of a single β-N-acetylglucosamine moiety to serine or threonine residues in nuclear and cytoplasmic proteins. 25520704 9 71 theme transcript 1301:1310 arg1 levels 1312:1317 OGT transcript levels 1297:1317 OGT transcript levels 1297:1317 OGT transcript levels slightly declined with TMG treatment, but OGA transcript levels were significantly increased. 25520704 10 72 theme inhibitor 1456:1464 arg1 cycloheximide 1466:1478 protein translation inhibitor cycloheximide 1436:1478 protein translation inhibitor cycloheximide 1436:1478 Pretreating cells with protein translation inhibitor cycloheximide did not stabilize OGT or OGA protein expression in the presence of TMG; nor did TMG stabilize OGT and OGA mRNA levels when cells were treated with RNA transcription inhibitor actinomycin D. Finally, we performed RNA Polymerase II chromatin immunoprecipitation at the OGA promoter and found that RNA Pol II occupancy at the transcription start site was lower after prolonged TMG treatment. 25520704 5 73 theme O-GlcNAc 826:833 arg1 homeostasis 835:845 O-GlcNAc homeostasis 826:845 O-GlcNAc homeostasis 826:845 Disruptions in O-GlcNAc homeostasis are proposed to lead to the development of diseases, such as cancer, diabetes, and Alzheimer's disease. 25520704 1 74 dep serine 217:222 arg1 residues 237:244 residues 237:244 residues 237:244 O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification involving an attachment of a single β-N-acetylglucosamine moiety to serine or threonine residues in nuclear and cytoplasmic proteins. 25520704 10 75 theme prolonged 1844:1852 arg1 treatment 1858:1866 prolonged TMG treatment 1844:1866 prolonged TMG treatment 1844:1866 Pretreating cells with protein translation inhibitor cycloheximide did not stabilize OGT or OGA protein expression in the presence of TMG; nor did TMG stabilize OGT and OGA mRNA levels when cells were treated with RNA transcription inhibitor actinomycin D. Finally, we performed RNA Polymerase II chromatin immunoprecipitation at the OGA promoter and found that RNA Pol II occupancy at the transcription start site was lower after prolonged TMG treatment. 25520704 4 76 theme cycle 754:758 arg1 progress 760:767 cell cycle progress 749:767 cell cycle progress 749:767 This process termed O-GlcNAc homeostasis appears to be critical to the regulation of many cellular functions including cell cycle progress, stress response, and gene transcription. 25520704 11 77 theme OGA 1903:1905 arg1 transcription 1907:1919 OGA transcription 1903:1919 OGA transcription 1903:1919 Together, these data suggest that OGA transcription was sensitive to changes in O-GlcNAc homeostasis and was potentially regulated by O-GlcNAc. 25520704 0 78 theme O-GlcNAc 50:57 arg1 Homeostasis 59:69 O-GlcNAc Homeostasis 50:69 O-GlcNAc Homeostasis 50:69 O-GlcNAcase Expression is Sensitive to Changes in O-GlcNAc Homeostasis. 25520704 9 79 theme OGT 1297:1299 arg1 levels 1312:1317 OGT transcript levels 1297:1317 OGT transcript levels 1297:1317 OGT transcript levels slightly declined with TMG treatment, but OGA transcript levels were significantly increased. 25520704 10 80 theme protein 1509:1515 arg1 expression 1517:1526 OGA protein expression 1505:1526 OGA protein expression 1505:1526 Pretreating cells with protein translation inhibitor cycloheximide did not stabilize OGT or OGA protein expression in the presence of TMG; nor did TMG stabilize OGT and OGA mRNA levels when cells were treated with RNA transcription inhibitor actinomycin D. Finally, we performed RNA Polymerase II chromatin immunoprecipitation at the OGA promoter and found that RNA Pol II occupancy at the transcription start site was lower after prolonged TMG treatment. 25520704 9 81 theme transcript 1365:1374 arg1 levels 1376:1381 OGA transcript levels 1361:1381 OGA transcript levels 1361:1381 OGT transcript levels slightly declined with TMG treatment, but OGA transcript levels were significantly increased. 25520704 8 82 theme human 1121:1125 arg1 lines 1132:1136 several human cell lines 1113:1136 several human cell lines with Thiamet-G (TMG, an OGA inhibitor) 1113:1175 We treated several human cell lines with Thiamet-G (TMG, an OGA inhibitor) to increase overall O-GlcNAc levels resulting in decreased OGT protein expression and increased OGA protein expression. 25520704 10 83 theme TMG 1547:1549 arg1 presence 1535:1542 the presence 1531:1542 the presence of TMG 1531:1549 Pretreating cells with protein translation inhibitor cycloheximide did not stabilize OGT or OGA protein expression in the presence of TMG; nor did TMG stabilize OGT and OGA mRNA levels when cells were treated with RNA transcription inhibitor actinomycin D. Finally, we performed RNA Polymerase II chromatin immunoprecipitation at the OGA promoter and found that RNA Pol II occupancy at the transcription start site was lower after prolonged TMG treatment. 25520704 10 84 theme chromatin 1710:1718 arg1 immunoprecipitation 1720:1738 RNA Polymerase II chromatin immunoprecipitation 1692:1738 RNA Polymerase II chromatin immunoprecipitation 1692:1738 Pretreating cells with protein translation inhibitor cycloheximide did not stabilize OGT or OGA protein expression in the presence of TMG; nor did TMG stabilize OGT and OGA mRNA levels when cells were treated with RNA transcription inhibitor actinomycin D. Finally, we performed RNA Polymerase II chromatin immunoprecipitation at the OGA promoter and found that RNA Pol II occupancy at the transcription start site was lower after prolonged TMG treatment. 25520704 1 85 theme cytoplasmic 261:271 arg1 proteins 273:280 nuclear and cytoplasmic proteins 249:280 nuclear and cytoplasmic proteins 249:280 O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification involving an attachment of a single β-N-acetylglucosamine moiety to serine or threonine residues in nuclear and cytoplasmic proteins. 24508798 0 0 theme high 70:73 arg1 glucose 75:81 high glucose 70:81 high glucose in HepG2 cells 70:96 Development of in vitro model of insulin receptor cleavage induced by high glucose in HepG2 cells. 24508798 4 1 theme cell 607:610 arg1 lines 612:616 four human cell lines 596:616 four human cell lines that expressed IR 596:634 Among four human cell lines that expressed IR, spontaneous cleavage of IR occurred only in HepG2 cells. 24508798 9 2 theme O-linked 1256:1263 arg1 modification 1285:1296 O-linked N-acetylglucosamine modification 1256:1296 O-linked N-acetylglucosamine modification 1256:1296 Using this model, O-linked N-acetylglucosamine modification was determined to be involved in high-glucose-induced IR cleavage. 24508798 2 3 theme insulin 407:413 arg1 resistance 415:424 insulin resistance 407:424 insulin resistance 407:424 IR has a pivotal role in glucose homeostasis and diabetes development; therefore, cleavage of IR promoted by hyperglycemia is involved in insulin resistance and glucose toxicity. 24508798 2 4 contain has 272:274 arg2 role 286:289 a pivotal role 276:289 a pivotal role 276:289 IR has a pivotal role in glucose homeostasis and diabetes development; therefore, cleavage of IR promoted by hyperglycemia is involved in insulin resistance and glucose toxicity. 24508798 2 4 contain has 272:274 arg1 IR 269:270 IR 269:270 IR 269:270 IR has a pivotal role in glucose homeostasis and diabetes development; therefore, cleavage of IR promoted by hyperglycemia is involved in insulin resistance and glucose toxicity. 24508798 2 5 theme pivotal 278:284 arg1 role 286:289 a pivotal role 276:289 a pivotal role 276:289 IR has a pivotal role in glucose homeostasis and diabetes development; therefore, cleavage of IR promoted by hyperglycemia is involved in insulin resistance and glucose toxicity. 24508798 6 6 theme basal 873:877 arg1 conditions 896:905 basal and high-glucose conditions 873:905 basal and high-glucose conditions 873:905 The concentration of sIR in the medium did not differ between basal and high-glucose conditions in the initial 24-h period, but increasing the duration of pre-stimulation (>48 h) led to a significant increase in sIR levels in cells exposed to high glucose. 24508798 6 7 theme pre-stimulation 966:980 arg1 duration 954:961 the duration 950:961 the duration of pre-stimulation (>48 h) 950:988 The concentration of sIR in the medium did not differ between basal and high-glucose conditions in the initial 24-h period, but increasing the duration of pre-stimulation (>48 h) led to a significant increase in sIR levels in cells exposed to high glucose. 24508798 3 8 theme sIR 540:542 arg1 levels 544:549 sIR levels 540:549 sIR levels 540:549 To elucidate the physiology of sIR, we developed an in vitro model mimicking the changes in sIR levels in plasma from patients with diabetes. 24508798 9 9 link O-linked 1256:1263 arg1 modification 1285:1296 O-linked N-acetylglucosamine modification 1256:1296 O-linked N-acetylglucosamine modification 1256:1296 Using this model, O-linked N-acetylglucosamine modification was determined to be involved in high-glucose-induced IR cleavage. 24508798 8 10 theme plasma 1200:1205 arg1 sIR 1207:1209 plasma sIR 1200:1209 plasma sIR 1200:1209 These results are consistent with the observation of plasma sIR in patients with diabetes. 24508798 4 11 theme IR 661:662 arg1 cleavage 649:656 spontaneous cleavage 637:656 spontaneous cleavage of IR 637:662 Among four human cell lines that expressed IR, spontaneous cleavage of IR occurred only in HepG2 cells. 24508798 6 12 theme high 1054:1057 arg1 glucose 1059:1065 high glucose 1054:1065 high glucose 1054:1065 The concentration of sIR in the medium did not differ between basal and high-glucose conditions in the initial 24-h period, but increasing the duration of pre-stimulation (>48 h) led to a significant increase in sIR levels in cells exposed to high glucose. 24508798 3 13 theme sIR 479:481 arg1 physiology 465:474 the physiology 461:474 the physiology of sIR 461:481 To elucidate the physiology of sIR, we developed an in vitro model mimicking the changes in sIR levels in plasma from patients with diabetes. 24508798 3 14 with patients 566:573 arg1 diabetes 580:587 diabetes 580:587 diabetes 580:587 To elucidate the physiology of sIR, we developed an in vitro model mimicking the changes in sIR levels in plasma from patients with diabetes. 24508798 8 15 with patients 1214:1221 arg1 diabetes 1228:1235 diabetes 1228:1235 diabetes 1228:1235 These results are consistent with the observation of plasma sIR in patients with diabetes. 24508798 9 16 theme IR 1352:1353 arg1 cleavage 1355:1362 high-glucose-induced IR cleavage 1331:1362 high-glucose-induced IR cleavage 1331:1362 Using this model, O-linked N-acetylglucosamine modification was determined to be involved in high-glucose-induced IR cleavage. 24508798 6 17 from levels 1027:1032 arg1 cells 1037:1041 cells 1037:1041 cells exposed to high glucose 1037:1065 The concentration of sIR in the medium did not differ between basal and high-glucose conditions in the initial 24-h period, but increasing the duration of pre-stimulation (>48 h) led to a significant increase in sIR levels in cells exposed to high glucose. 24508798 1 18 with patients 245:252 arg1 diabetes 259:266 diabetes 259:266 diabetes 259:266 Soluble insulin receptor (sIR), the ectodomain of IR, has been detected in human plasma, and its concentration parallels that of blood glucose in patients with diabetes. 24508798 3 19 from changes 529:535 arg1 plasma 554:559 plasma 554:559 plasma from patients with diabetes 554:587 To elucidate the physiology of sIR, we developed an in vitro model mimicking the changes in sIR levels in plasma from patients with diabetes. 24508798 3 19 from changes 529:535 arg1 levels 544:549 sIR levels 540:549 sIR levels 540:549 To elucidate the physiology of sIR, we developed an in vitro model mimicking the changes in sIR levels in plasma from patients with diabetes. 24508798 3 19 from changes 529:535 arg1 patients 566:573 patients 566:573 patients with diabetes 566:587 To elucidate the physiology of sIR, we developed an in vitro model mimicking the changes in sIR levels in plasma from patients with diabetes. 24508798 3 20 dep in 500:501 arg1 vitro 503:507 vitro 503:507 vitro 503:507 To elucidate the physiology of sIR, we developed an in vitro model mimicking the changes in sIR levels in plasma from patients with diabetes. 24508798 0 21 theme HepG2 86:90 arg1 cells 92:96 HepG2 cells 86:96 HepG2 cells 86:96 Development of in vitro model of insulin receptor cleavage induced by high glucose in HepG2 cells. 24508798 11 22 theme IR 1546:1547 arg1 cleavage 1549:1556 IR cleavage 1546:1556 IR cleavage 1546:1556 These findings show that this in vitro model could be useful for determining the molecular mechanism underlying IR cleavage. 24508798 1 23 from glucose 234:240 arg1 patients 245:252 patients 245:252 patients with diabetes 245:266 Soluble insulin receptor (sIR), the ectodomain of IR, has been detected in human plasma, and its concentration parallels that of blood glucose in patients with diabetes. 24508798 7 24 from reversible 1121:1130 arg1 model 1140:1144 this model 1135:1144 this model 1135:1144 Additionally, glucose-dependent increment of sIR was reversible in this model. 24508798 6 25 theme sIR 1023:1025 arg1 levels 1027:1032 sIR levels 1023:1032 sIR levels in cells exposed to high glucose 1023:1065 The concentration of sIR in the medium did not differ between basal and high-glucose conditions in the initial 24-h period, but increasing the duration of pre-stimulation (>48 h) led to a significant increase in sIR levels in cells exposed to high glucose. 24508798 2 26 theme diabetes 318:325 arg1 development 327:337 diabetes development 318:337 diabetes development 318:337 IR has a pivotal role in glucose homeostasis and diabetes development; therefore, cleavage of IR promoted by hyperglycemia is involved in insulin resistance and glucose toxicity. 24508798 5 27 theme molecular 698:706 arg1 characteristics 708:722 The molecular characteristics 694:722 The molecular characteristics of sIR derived from HepG2 cells 694:754 The molecular characteristics of sIR derived from HepG2 cells were similar to those of sIR detected in human plasma. 24508798 5 27 theme molecular 698:706 arg1 similar 761:767 similar 761:767 similar 761:767 The molecular characteristics of sIR derived from HepG2 cells were similar to those of sIR detected in human plasma. 24508798 5 28 located detected 785:792 arg1 plasma 803:808 human plasma 797:808 human plasma 797:808 The molecular characteristics of sIR derived from HepG2 cells were similar to those of sIR detected in human plasma. 24508798 5 28 located detected 785:792 arg2 sIR 781:783 sIR 781:783 sIR detected in human plasma 781:808 The molecular characteristics of sIR derived from HepG2 cells were similar to those of sIR detected in human plasma. 24508798 3 29 from patients 566:573 arg1 plasma 554:559 plasma 554:559 plasma from patients with diabetes 554:587 To elucidate the physiology of sIR, we developed an in vitro model mimicking the changes in sIR levels in plasma from patients with diabetes. 24508798 3 29 from patients 566:573 arg1 changes 529:535 the changes 525:535 the changes in sIR levels in plasma from patients with diabetes 525:587 To elucidate the physiology of sIR, we developed an in vitro model mimicking the changes in sIR levels in plasma from patients with diabetes. 24508798 4 30 theme spontaneous 637:647 arg1 cleavage 649:656 spontaneous cleavage 637:656 spontaneous cleavage of IR 637:662 Among four human cell lines that expressed IR, spontaneous cleavage of IR occurred only in HepG2 cells. 24508798 4 31 theme HepG2 681:685 arg1 cells 687:691 HepG2 cells 681:691 HepG2 cells 681:691 Among four human cell lines that expressed IR, spontaneous cleavage of IR occurred only in HepG2 cells. 24508798 8 32 with consistent 1165:1174 arg1 observation 1185:1195 the observation 1181:1195 the observation of plasma sIR in patients with diabetes 1181:1235 These results are consistent with the observation of plasma sIR in patients with diabetes. 24508798 1 33 theme IR 149:150 arg1 receptor 115:122 Soluble insulin receptor 99:122 Soluble insulin receptor (sIR) 99:128 Soluble insulin receptor (sIR), the ectodomain of IR, has been detected in human plasma, and its concentration parallels that of blood glucose in patients with diabetes. 24508798 1 33 theme IR 149:150 arg1 ectodomain 135:144 the ectodomain 131:144 the ectodomain of IR 131:150 Soluble insulin receptor (sIR), the ectodomain of IR, has been detected in human plasma, and its concentration parallels that of blood glucose in patients with diabetes. 24508798 1 33 theme IR 149:150 arg1 IR 149:150 IR 149:150 IR 149:150 Soluble insulin receptor (sIR), the ectodomain of IR, has been detected in human plasma, and its concentration parallels that of blood glucose in patients with diabetes. 24508798 2 34 theme IR 363:364 arg1 cleavage 351:358 cleavage 351:358 cleavage of IR promoted by hyperglycemia 351:390 IR has a pivotal role in glucose homeostasis and diabetes development; therefore, cleavage of IR promoted by hyperglycemia is involved in insulin resistance and glucose toxicity. 24508798 7 35 from model 1140:1144 arg1 reversible 1121:1130 reversible 1121:1130 reversible 1121:1130 Additionally, glucose-dependent increment of sIR was reversible in this model. 24508798 6 36 theme significant 999:1009 arg1 increase 1011:1018 a significant increase 997:1018 a significant increase in sIR levels in cells exposed to high glucose 997:1065 The concentration of sIR in the medium did not differ between basal and high-glucose conditions in the initial 24-h period, but increasing the duration of pre-stimulation (>48 h) led to a significant increase in sIR levels in cells exposed to high glucose. 24508798 9 37 theme high-glucose-induced 1331:1350 arg1 cleavage 1355:1362 high-glucose-induced IR cleavage 1331:1362 high-glucose-induced IR cleavage 1331:1362 Using this model, O-linked N-acetylglucosamine modification was determined to be involved in high-glucose-induced IR cleavage. 24508798 0 38 theme in 15:16 arg1 model 24:28 in vitro model 15:28 in vitro model of insulin receptor cleavage 15:57 Development of in vitro model of insulin receptor cleavage induced by high glucose in HepG2 cells. 24508798 1 39 theme blood 228:232 arg1 glucose 234:240 blood glucose 228:240 blood glucose in patients with diabetes 228:266 Soluble insulin receptor (sIR), the ectodomain of IR, has been detected in human plasma, and its concentration parallels that of blood glucose in patients with diabetes. 24508798 10 40 theme calcium-dependent 1367:1383 arg1 protease 1385:1392 A calcium-dependent protease 1365:1392 A calcium-dependent protease 1365:1392 A calcium-dependent protease was shown to cleave IR extracellularly. 24508798 4 41 theme human 601:605 arg1 lines 612:616 four human cell lines 596:616 four human cell lines that expressed IR 596:634 Among four human cell lines that expressed IR, spontaneous cleavage of IR occurred only in HepG2 cells. 24508798 7 42 theme sIR 1113:1115 arg1 increment 1100:1108 glucose-dependent increment 1082:1108 glucose-dependent increment of sIR 1082:1115 Additionally, glucose-dependent increment of sIR was reversible in this model. 24508798 6 43 theme 24-h 922:925 arg1 period 927:932 the initial 24-h period 910:932 the initial 24-h period 910:932 The concentration of sIR in the medium did not differ between basal and high-glucose conditions in the initial 24-h period, but increasing the duration of pre-stimulation (>48 h) led to a significant increase in sIR levels in cells exposed to high glucose. 24508798 6 44 from increase 1011:1018 arg1 levels 1027:1032 sIR levels 1023:1032 sIR levels in cells exposed to high glucose 1023:1065 The concentration of sIR in the medium did not differ between basal and high-glucose conditions in the initial 24-h period, but increasing the duration of pre-stimulation (>48 h) led to a significant increase in sIR levels in cells exposed to high glucose. 24508798 5 45 theme HepG2 744:748 arg1 cells 750:754 HepG2 cells 744:754 HepG2 cells 744:754 The molecular characteristics of sIR derived from HepG2 cells were similar to those of sIR detected in human plasma. 24508798 0 46 theme model 24:28 arg1 Development 0:10 Development 0:10 Development of in vitro model of insulin receptor cleavage 0:57 Development of in vitro model of insulin receptor cleavage induced by high glucose in HepG2 cells. 24508798 9 47 theme N-acetylglucosamine 1265:1283 arg1 modification 1285:1296 O-linked N-acetylglucosamine modification 1256:1296 O-linked N-acetylglucosamine modification 1256:1296 Using this model, O-linked N-acetylglucosamine modification was determined to be involved in high-glucose-induced IR cleavage. 24508798 11 48 theme molecular 1515:1523 arg1 mechanism 1525:1533 the molecular mechanism 1511:1533 the molecular mechanism underlying IR cleavage 1511:1556 These findings show that this in vitro model could be useful for determining the molecular mechanism underlying IR cleavage. 24508798 6 49 theme initial 914:920 arg1 period 927:932 the initial 24-h period 910:932 the initial 24-h period 910:932 The concentration of sIR in the medium did not differ between basal and high-glucose conditions in the initial 24-h period, but increasing the duration of pre-stimulation (>48 h) led to a significant increase in sIR levels in cells exposed to high glucose. 24508798 0 50 theme receptor 41:48 arg1 cleavage 50:57 insulin receptor cleavage 33:57 insulin receptor cleavage 33:57 Development of in vitro model of insulin receptor cleavage induced by high glucose in HepG2 cells. 24508798 6 51 theme sIR 832:834 arg1 concentration 815:827 The concentration 811:827 The concentration of sIR in the medium 811:848 The concentration of sIR in the medium did not differ between basal and high-glucose conditions in the initial 24-h period, but increasing the duration of pre-stimulation (>48 h) led to a significant increase in sIR levels in cells exposed to high glucose. 24508798 7 52 theme glucose-dependent 1082:1098 arg1 increment 1100:1108 glucose-dependent increment 1082:1108 glucose-dependent increment of sIR 1082:1115 Additionally, glucose-dependent increment of sIR was reversible in this model. 24508798 3 53 theme in 500:501 arg1 model 509:513 an in vitro model 497:513 an in vitro model mimicking the changes in sIR levels in plasma from patients with diabetes 497:587 To elucidate the physiology of sIR, we developed an in vitro model mimicking the changes in sIR levels in plasma from patients with diabetes. 24508798 5 54 theme human 797:801 arg1 plasma 803:808 human plasma 797:808 human plasma 797:808 The molecular characteristics of sIR derived from HepG2 cells were similar to those of sIR detected in human plasma. 24508798 0 55 theme insulin 33:39 arg1 cleavage 50:57 insulin receptor cleavage 33:57 insulin receptor cleavage 33:57 Development of in vitro model of insulin receptor cleavage induced by high glucose in HepG2 cells. 24508798 6 56 from concentration 815:827 arg1 medium 843:848 the medium 839:848 the medium 839:848 The concentration of sIR in the medium did not differ between basal and high-glucose conditions in the initial 24-h period, but increasing the duration of pre-stimulation (>48 h) led to a significant increase in sIR levels in cells exposed to high glucose. 24508798 11 57 theme in 1464:1465 arg1 model 1473:1477 this in vitro model 1459:1477 this in vitro model 1459:1477 These findings show that this in vitro model could be useful for determining the molecular mechanism underlying IR cleavage. 24508798 1 58 theme Soluble 99:105 arg1 sIR 125:127 sIR 125:127 sIR 125:127 Soluble insulin receptor (sIR), the ectodomain of IR, has been detected in human plasma, and its concentration parallels that of blood glucose in patients with diabetes. 24508798 1 58 theme Soluble 99:105 arg1 receptor 115:122 Soluble insulin receptor 99:122 Soluble insulin receptor (sIR) 99:128 Soluble insulin receptor (sIR), the ectodomain of IR, has been detected in human plasma, and its concentration parallels that of blood glucose in patients with diabetes. 24508798 1 58 theme Soluble 99:105 arg1 ectodomain 135:144 the ectodomain 131:144 the ectodomain of IR 131:150 Soluble insulin receptor (sIR), the ectodomain of IR, has been detected in human plasma, and its concentration parallels that of blood glucose in patients with diabetes. 24508798 1 58 theme Soluble 99:105 arg1 IR 149:150 IR 149:150 IR 149:150 Soluble insulin receptor (sIR), the ectodomain of IR, has been detected in human plasma, and its concentration parallels that of blood glucose in patients with diabetes. 24508798 5 59 attach derived 731:737 arg2 sIR 727:729 sIR 727:729 sIR derived from HepG2 cells 727:754 The molecular characteristics of sIR derived from HepG2 cells were similar to those of sIR detected in human plasma. 24508798 5 59 attach derived 731:737 arg1 cells 750:754 HepG2 cells 744:754 HepG2 cells 744:754 The molecular characteristics of sIR derived from HepG2 cells were similar to those of sIR detected in human plasma. 24508798 1 60 theme insulin 107:113 arg1 sIR 125:127 sIR 125:127 sIR 125:127 Soluble insulin receptor (sIR), the ectodomain of IR, has been detected in human plasma, and its concentration parallels that of blood glucose in patients with diabetes. 24508798 1 60 theme insulin 107:113 arg1 receptor 115:122 Soluble insulin receptor 99:122 Soluble insulin receptor (sIR) 99:128 Soluble insulin receptor (sIR), the ectodomain of IR, has been detected in human plasma, and its concentration parallels that of blood glucose in patients with diabetes. 24508798 1 60 theme insulin 107:113 arg1 ectodomain 135:144 the ectodomain 131:144 the ectodomain of IR 131:150 Soluble insulin receptor (sIR), the ectodomain of IR, has been detected in human plasma, and its concentration parallels that of blood glucose in patients with diabetes. 24508798 1 60 theme insulin 107:113 arg1 IR 149:150 IR 149:150 IR 149:150 Soluble insulin receptor (sIR), the ectodomain of IR, has been detected in human plasma, and its concentration parallels that of blood glucose in patients with diabetes. 24508798 8 61 theme sIR 1207:1209 arg1 observation 1185:1195 the observation 1181:1195 the observation of plasma sIR in patients with diabetes 1181:1235 These results are consistent with the observation of plasma sIR in patients with diabetes. 24508798 1 62 located detected 162:169 arg1 plasma 180:185 human plasma 174:185 human plasma 174:185 Soluble insulin receptor (sIR), the ectodomain of IR, has been detected in human plasma, and its concentration parallels that of blood glucose in patients with diabetes. 24508798 1 62 located detected 162:169 arg2 IR 149:150 IR 149:150 IR 149:150 Soluble insulin receptor (sIR), the ectodomain of IR, has been detected in human plasma, and its concentration parallels that of blood glucose in patients with diabetes. 24508798 1 62 located detected 162:169 arg2 sIR 125:127 sIR 125:127 sIR 125:127 Soluble insulin receptor (sIR), the ectodomain of IR, has been detected in human plasma, and its concentration parallels that of blood glucose in patients with diabetes. 24508798 1 62 located detected 162:169 arg2 receptor 115:122 Soluble insulin receptor 99:122 Soluble insulin receptor (sIR) 99:128 Soluble insulin receptor (sIR), the ectodomain of IR, has been detected in human plasma, and its concentration parallels that of blood glucose in patients with diabetes. 24508798 1 62 located detected 162:169 arg2 ectodomain 135:144 the ectodomain 131:144 the ectodomain of IR 131:150 Soluble insulin receptor (sIR), the ectodomain of IR, has been detected in human plasma, and its concentration parallels that of blood glucose in patients with diabetes. 24508798 0 63 dep in 15:16 arg1 vitro 18:22 vitro 18:22 vitro 18:22 Development of in vitro model of insulin receptor cleavage induced by high glucose in HepG2 cells. 24508798 8 64 from observation 1185:1195 arg1 patients 1214:1221 patients 1214:1221 patients with diabetes 1214:1235 These results are consistent with the observation of plasma sIR in patients with diabetes. 24508798 11 65 dep in 1464:1465 arg1 vitro 1467:1471 vitro 1467:1471 vitro 1467:1471 These findings show that this in vitro model could be useful for determining the molecular mechanism underlying IR cleavage. 24508798 1 66 theme human 174:178 arg1 plasma 180:185 human plasma 174:185 human plasma 174:185 Soluble insulin receptor (sIR), the ectodomain of IR, has been detected in human plasma, and its concentration parallels that of blood glucose in patients with diabetes. 24508798 2 67 theme glucose 430:436 arg1 toxicity 438:445 glucose toxicity 430:445 glucose toxicity 430:445 IR has a pivotal role in glucose homeostasis and diabetes development; therefore, cleavage of IR promoted by hyperglycemia is involved in insulin resistance and glucose toxicity. 24508798 0 68 from glucose 75:81 arg1 cells 92:96 HepG2 cells 86:96 HepG2 cells 86:96 Development of in vitro model of insulin receptor cleavage induced by high glucose in HepG2 cells. 24508798 2 69 theme glucose 294:300 arg1 homeostasis 302:312 glucose homeostasis 294:312 glucose homeostasis 294:312 IR has a pivotal role in glucose homeostasis and diabetes development; therefore, cleavage of IR promoted by hyperglycemia is involved in insulin resistance and glucose toxicity. 24508798 0 70 theme cleavage 50:57 arg1 model 24:28 in vitro model 15:28 in vitro model of insulin receptor cleavage 15:57 Development of in vitro model of insulin receptor cleavage induced by high glucose in HepG2 cells. 24508798 5 71 theme sIR 727:729 arg1 characteristics 708:722 The molecular characteristics 694:722 The molecular characteristics of sIR derived from HepG2 cells 694:754 The molecular characteristics of sIR derived from HepG2 cells were similar to those of sIR detected in human plasma. 24508798 5 71 theme sIR 727:729 arg1 similar 761:767 similar 761:767 similar 761:767 The molecular characteristics of sIR derived from HepG2 cells were similar to those of sIR detected in human plasma. 24508798 6 72 theme high-glucose 883:894 arg1 conditions 896:905 basal and high-glucose conditions 873:905 basal and high-glucose conditions 873:905 The concentration of sIR in the medium did not differ between basal and high-glucose conditions in the initial 24-h period, but increasing the duration of pre-stimulation (>48 h) led to a significant increase in sIR levels in cells exposed to high glucose. 26309284 3 0 theme oviposition 443:453 arg1 oviposition 443:453 oviposition 443:453 oviposition 443:453 A heat-stable factor that can migrate from the site of oviposition in the trunk through the xylem to needles in the crown of attacked pines was purified by size-fractionation and reversed-phase-high-performance liquid chromatography using activity assays based on defense gene induction as well as the needle wilt response in pine shoot explants. 26309284 3 0 theme oviposition 443:453 arg1 site 435:438 the site 431:438 the site of oviposition in the trunk 431:466 A heat-stable factor that can migrate from the site of oviposition in the trunk through the xylem to needles in the crown of attacked pines was purified by size-fractionation and reversed-phase-high-performance liquid chromatography using activity assays based on defense gene induction as well as the needle wilt response in pine shoot explants. 26309284 7 1 theme pine 1398:1401 arg1 genes 1411:1415 pine defense genes 1398:1415 pine defense genes 1398:1415 In contrast to the native peptide, a synthetic version of the hydroxylated peptide backbone lacking the glycosyl side chains failed to induce pine defense genes or cause needle wilt in excised shoots. 26309284 7 2 theme needle 1426:1431 arg1 wilt 1433:1436 needle wilt 1426:1436 needle wilt in excised shoots 1426:1454 In contrast to the native peptide, a synthetic version of the hydroxylated peptide backbone lacking the glycosyl side chains failed to induce pine defense genes or cause needle wilt in excised shoots. 26309284 6 3 theme C6 1208:1209 arg1 position 1211:1218 the C6 position 1204:1218 the C6 position 1204:1218 The O-linked sugars were identical α-linked N-acetylgalactosamine residues modified at the C6 position by addition of phosphoethanolamine. 26309284 1 4 theme female 153:158 arg1 noctilio 166:173 female Sirex noctilio 153:173 female Sirex noctilio (F.) (Siricidae) 153:190 During oviposition, female Sirex noctilio (F.) (Siricidae) woodwasps inject their conifer hosts with a venom gland secretion. 26309284 1 4 theme female 153:158 arg1 Siricidae 181:189 Siricidae 181:189 Siricidae 181:189 During oviposition, female Sirex noctilio (F.) (Siricidae) woodwasps inject their conifer hosts with a venom gland secretion. 26309284 4 5 theme gland 877:881 arg1 tissue 883:888 S. noctilio venom gland tissue 859:888 S. noctilio venom gland tissue 859:888 An 11-amino acid, posttranslationally modified peptide (SEGPROGTKRP) encoded by the most abundant transcript recovered from S. noctilio venom gland tissue comprised the backbone of the 1,850 Da active factor. 26309284 1 6 with hosts 223:227 arg1 secretion 248:256 a venom gland secretion 234:256 a venom gland secretion 234:256 During oviposition, female Sirex noctilio (F.) (Siricidae) woodwasps inject their conifer hosts with a venom gland secretion. 26309284 7 7 theme glycosyl 1360:1367 arg1 chains 1374:1379 the glycosyl side chains 1356:1379 the glycosyl side chains 1356:1379 In contrast to the native peptide, a synthetic version of the hydroxylated peptide backbone lacking the glycosyl side chains failed to induce pine defense genes or cause needle wilt in excised shoots. 26309284 3 8 theme needle 690:695 arg1 response 702:709 the needle wilt response 686:709 defense gene induction as well as the needle wilt response in pine shoot explants 652:732 A heat-stable factor that can migrate from the site of oviposition in the trunk through the xylem to needles in the crown of attacked pines was purified by size-fractionation and reversed-phase-high-performance liquid chromatography using activity assays based on defense gene induction as well as the needle wilt response in pine shoot explants. 26309284 5 9 from hydroxylation 985:997 arg1 position 1019:1026 position 6 1019:1028 position 6 1019:1028 Posttranslational modifications included hydroxylation of a Pro residue at position 6 as well as O-glycosylation of Ser and Thr residues at positions 1 and 8, respectively. 26309284 5 9 from hydroxylation 985:997 arg1 positions 1084:1092 positions 1 and 8 1084:1100 positions 1 and 8 1084:1100 Posttranslational modifications included hydroxylation of a Pro residue at position 6 as well as O-glycosylation of Ser and Thr residues at positions 1 and 8, respectively. 26309284 7 10 from wilt 1433:1436 arg1 shoots 1449:1454 excised shoots 1441:1454 excised shoots 1441:1454 In contrast to the native peptide, a synthetic version of the hydroxylated peptide backbone lacking the glycosyl side chains failed to induce pine defense genes or cause needle wilt in excised shoots. 26309284 9 11 theme pine 1692:1695 arg1 systems 1705:1711 pine defense systems 1692:1711 pine defense systems 1692:1711 The noctilisin structure contains motifs which may explain how it avoids detection by pine defense systems. 26309284 9 12 contain contains 1631:1638 arg2 motifs 1640:1645 motifs 1640:1645 motifs which may explain how it avoids detection by pine defense systems 1640:1711 The noctilisin structure contains motifs which may explain how it avoids detection by pine defense systems. 26309284 9 12 contain contains 1631:1638 arg1 structure 1621:1629 The noctilisin structure 1606:1629 The noctilisin structure 1606:1629 The noctilisin structure contains motifs which may explain how it avoids detection by pine defense systems. 26309284 0 13 theme Defense 100:106 arg1 Responses 113:121 Defense Gene Responses 100:121 Defense Gene Responses 100:121 Noctilisin, a Venom Glycopeptide of Sirex noctilio (Hymenoptera: Siricidae), Causes Needle Wilt and Defense Gene Responses in Pines. 26309284 3 14 theme pines 522:526 arg1 crown 504:508 the crown 500:508 the crown of attacked pines 500:526 A heat-stable factor that can migrate from the site of oviposition in the trunk through the xylem to needles in the crown of attacked pines was purified by size-fractionation and reversed-phase-high-performance liquid chromatography using activity assays based on defense gene induction as well as the needle wilt response in pine shoot explants. 26309284 3 15 theme shoot 719:723 arg1 explants 725:732 pine shoot explants 714:732 pine shoot explants 714:732 A heat-stable factor that can migrate from the site of oviposition in the trunk through the xylem to needles in the crown of attacked pines was purified by size-fractionation and reversed-phase-high-performance liquid chromatography using activity assays based on defense gene induction as well as the needle wilt response in pine shoot explants. 26309284 7 16 theme peptide 1331:1337 arg1 backbone 1339:1346 the hydroxylated peptide backbone 1314:1346 the hydroxylated peptide backbone lacking the glycosyl side chains 1314:1379 In contrast to the native peptide, a synthetic version of the hydroxylated peptide backbone lacking the glycosyl side chains failed to induce pine defense genes or cause needle wilt in excised shoots. 26309284 3 17 from induction 665:673 arg1 explants 725:732 pine shoot explants 714:732 pine shoot explants 714:732 A heat-stable factor that can migrate from the site of oviposition in the trunk through the xylem to needles in the crown of attacked pines was purified by size-fractionation and reversed-phase-high-performance liquid chromatography using activity assays based on defense gene induction as well as the needle wilt response in pine shoot explants. 26309284 3 18 theme pine 714:717 arg1 explants 725:732 pine shoot explants 714:732 pine shoot explants 714:732 A heat-stable factor that can migrate from the site of oviposition in the trunk through the xylem to needles in the crown of attacked pines was purified by size-fractionation and reversed-phase-high-performance liquid chromatography using activity assays based on defense gene induction as well as the needle wilt response in pine shoot explants. 26309284 5 19 theme residue 1008:1014 arg1 hydroxylation 985:997 hydroxylation 985:997 hydroxylation of a Pro residue at position 6 as well as O-glycosylation of Ser and Thr residues at positions 1 and 8 985:1100 Posttranslational modifications included hydroxylation of a Pro residue at position 6 as well as O-glycosylation of Ser and Thr residues at positions 1 and 8, respectively. 26309284 4 20 theme noctilio 862:869 arg1 tissue 883:888 S. noctilio venom gland tissue 859:888 S. noctilio venom gland tissue 859:888 An 11-amino acid, posttranslationally modified peptide (SEGPROGTKRP) encoded by the most abundant transcript recovered from S. noctilio venom gland tissue comprised the backbone of the 1,850 Da active factor. 26309284 6 21 theme N-acetylgalactosamine 1161:1181 arg1 residues 1183:1190 identical α-linked N-acetylgalactosamine residues 1142:1190 identical α-linked N-acetylgalactosamine residues modified at the C6 position by addition of phosphoethanolamine 1142:1253 The O-linked sugars were identical α-linked N-acetylgalactosamine residues modified at the C6 position by addition of phosphoethanolamine. 26309284 6 21 theme N-acetylgalactosamine 1161:1181 arg1 sugars 1130:1135 The O-linked sugars 1117:1135 The O-linked sugars 1117:1135 The O-linked sugars were identical α-linked N-acetylgalactosamine residues modified at the C6 position by addition of phosphoethanolamine. 26309284 3 22 from needles 489:495 arg1 crown 504:508 the crown 500:508 the crown of attacked pines 500:526 A heat-stable factor that can migrate from the site of oviposition in the trunk through the xylem to needles in the crown of attacked pines was purified by size-fractionation and reversed-phase-high-performance liquid chromatography using activity assays based on defense gene induction as well as the needle wilt response in pine shoot explants. 26309284 3 23 theme size-fractionation 544:561 arg1 chromatography 606:619 size-fractionation and reversed-phase-high-performance liquid chromatography 544:619 size-fractionation and reversed-phase-high-performance liquid chromatography 544:619 A heat-stable factor that can migrate from the site of oviposition in the trunk through the xylem to needles in the crown of attacked pines was purified by size-fractionation and reversed-phase-high-performance liquid chromatography using activity assays based on defense gene induction as well as the needle wilt response in pine shoot explants. 26309284 4 24 theme Da 926:927 arg1 factor 936:941 the 1,850 Da active factor 916:941 the 1,850 Da active factor 916:941 An 11-amino acid, posttranslationally modified peptide (SEGPROGTKRP) encoded by the most abundant transcript recovered from S. noctilio venom gland tissue comprised the backbone of the 1,850 Da active factor. 26309284 6 25 theme identical 1142:1150 arg1 residues 1183:1190 identical α-linked N-acetylgalactosamine residues 1142:1190 identical α-linked N-acetylgalactosamine residues modified at the C6 position by addition of phosphoethanolamine 1142:1253 The O-linked sugars were identical α-linked N-acetylgalactosamine residues modified at the C6 position by addition of phosphoethanolamine. 26309284 6 25 theme identical 1142:1150 arg1 sugars 1130:1135 The O-linked sugars 1117:1135 The O-linked sugars 1117:1135 The O-linked sugars were identical α-linked N-acetylgalactosamine residues modified at the C6 position by addition of phosphoethanolamine. 26309284 5 26 theme residues 1072:1079 arg1 residue 1008:1014 a Pro residue 1002:1014 a Pro residue at position 6 as well as O-glycosylation of Ser and Thr residues at positions 1 and 8 1002:1100 Posttranslational modifications included hydroxylation of a Pro residue at position 6 as well as O-glycosylation of Ser and Thr residues at positions 1 and 8, respectively. 26309284 5 26 theme residues 1072:1079 arg1 Ser 1060:1062 Ser 1060:1062 Ser 1060:1062 Posttranslational modifications included hydroxylation of a Pro residue at position 6 as well as O-glycosylation of Ser and Thr residues at positions 1 and 8, respectively. 26309284 5 26 theme residues 1072:1079 arg1 residues 1072:1079 Thr residues 1068:1079 Thr residues 1068:1079 Posttranslational modifications included hydroxylation of a Pro residue at position 6 as well as O-glycosylation of Ser and Thr residues at positions 1 and 8, respectively. 26309284 5 26 theme residues 1072:1079 arg1 O-glycosylation 1041:1055 O-glycosylation 1041:1055 a Pro residue at position 6 as well as O-glycosylation of Ser and Thr residues at positions 1 and 8 1002:1100 Posttranslational modifications included hydroxylation of a Pro residue at position 6 as well as O-glycosylation of Ser and Thr residues at positions 1 and 8, respectively. 26309284 4 27 theme factor 936:941 arg1 backbone 904:911 the backbone 900:911 the backbone of the 1,850 Da active factor 900:941 An 11-amino acid, posttranslationally modified peptide (SEGPROGTKRP) encoded by the most abundant transcript recovered from S. noctilio venom gland tissue comprised the backbone of the 1,850 Da active factor. 26309284 7 28 theme hydroxylated 1318:1329 arg1 backbone 1339:1346 the hydroxylated peptide backbone 1314:1346 the hydroxylated peptide backbone lacking the glycosyl side chains 1314:1379 In contrast to the native peptide, a synthetic version of the hydroxylated peptide backbone lacking the glycosyl side chains failed to induce pine defense genes or cause needle wilt in excised shoots. 26309284 7 29 theme defense 1403:1409 arg1 genes 1411:1415 pine defense genes 1398:1415 pine defense genes 1398:1415 In contrast to the native peptide, a synthetic version of the hydroxylated peptide backbone lacking the glycosyl side chains failed to induce pine defense genes or cause needle wilt in excised shoots. 26309284 2 30 theme subsequent 337:346 arg1 infection 355:363 subsequent lethal infection 337:363 subsequent lethal infection 337:363 The secretion induces a variety of host physiological changes that facilitate subsequent lethal infection by a symbiotic fungus. 26309284 7 31 theme synthetic 1293:1301 arg1 version 1303:1309 a synthetic version 1291:1309 a synthetic version of the hydroxylated peptide backbone lacking the glycosyl side chains 1291:1379 In contrast to the native peptide, a synthetic version of the hydroxylated peptide backbone lacking the glycosyl side chains failed to induce pine defense genes or cause needle wilt in excised shoots. 26309284 3 32 from response 702:709 arg1 explants 725:732 pine shoot explants 714:732 pine shoot explants 714:732 A heat-stable factor that can migrate from the site of oviposition in the trunk through the xylem to needles in the crown of attacked pines was purified by size-fractionation and reversed-phase-high-performance liquid chromatography using activity assays based on defense gene induction as well as the needle wilt response in pine shoot explants. 26309284 1 33 theme conifer 215:221 arg1 hosts 223:227 their conifer hosts 209:227 their conifer hosts with a venom gland secretion 209:256 During oviposition, female Sirex noctilio (F.) (Siricidae) woodwasps inject their conifer hosts with a venom gland secretion. 26309284 7 34 theme native 1275:1280 arg1 peptide 1282:1288 the native peptide 1271:1288 the native peptide 1271:1288 In contrast to the native peptide, a synthetic version of the hydroxylated peptide backbone lacking the glycosyl side chains failed to induce pine defense genes or cause needle wilt in excised shoots. 26309284 4 35 theme modified 773:780 arg1 acid 747:750 An 11-amino acid 735:750 An 11-amino acid 735:750 An 11-amino acid, posttranslationally modified peptide (SEGPROGTKRP) encoded by the most abundant transcript recovered from S. noctilio venom gland tissue comprised the backbone of the 1,850 Da active factor. 26309284 4 35 theme modified 773:780 arg1 SEGPROGTKRP 791:801 SEGPROGTKRP 791:801 SEGPROGTKRP 791:801 An 11-amino acid, posttranslationally modified peptide (SEGPROGTKRP) encoded by the most abundant transcript recovered from S. noctilio venom gland tissue comprised the backbone of the 1,850 Da active factor. 26309284 4 35 theme modified 773:780 arg1 peptide 782:788 posttranslationally modified peptide 753:788 posttranslationally modified peptide (SEGPROGTKRP) encoded by the most abundant transcript recovered from S. noctilio venom gland tissue 753:888 An 11-amino acid, posttranslationally modified peptide (SEGPROGTKRP) encoded by the most abundant transcript recovered from S. noctilio venom gland tissue comprised the backbone of the 1,850 Da active factor. 26309284 3 36 theme heat-stable 390:400 arg1 factor 402:407 A heat-stable factor 388:407 A heat-stable factor that can migrate from the site of oviposition in the trunk through the xylem to needles in the crown of attacked pines 388:526 A heat-stable factor that can migrate from the site of oviposition in the trunk through the xylem to needles in the crown of attacked pines was purified by size-fractionation and reversed-phase-high-performance liquid chromatography using activity assays based on defense gene induction as well as the needle wilt response in pine shoot explants. 26309284 1 37 theme venom 236:240 arg1 secretion 248:256 a venom gland secretion 234:256 a venom gland secretion 234:256 During oviposition, female Sirex noctilio (F.) (Siricidae) woodwasps inject their conifer hosts with a venom gland secretion. 26309284 8 38 theme O-glycosylated 1518:1531 arg1 peptides 1572:1579 the O-glycosylated short-chain proline-rich antimicrobial peptides 1514:1579 the O-glycosylated short-chain proline-rich antimicrobial peptides exemplified by drosocin 1514:1603 This peptide, hereafter called noctilisin, is related to the O-glycosylated short-chain proline-rich antimicrobial peptides exemplified by drosocin. 26309284 3 39 theme reversed-phase-high-performance 567:597 arg1 chromatography 606:619 size-fractionation and reversed-phase-high-performance liquid chromatography 544:619 size-fractionation and reversed-phase-high-performance liquid chromatography 544:619 A heat-stable factor that can migrate from the site of oviposition in the trunk through the xylem to needles in the crown of attacked pines was purified by size-fractionation and reversed-phase-high-performance liquid chromatography using activity assays based on defense gene induction as well as the needle wilt response in pine shoot explants. 26309284 0 40 theme Sirex 36:40 arg1 noctilio 42:49 Sirex noctilio 36:49 Sirex noctilio (Hymenoptera: Siricidae) 36:74 Noctilisin, a Venom Glycopeptide of Sirex noctilio (Hymenoptera: Siricidae), Causes Needle Wilt and Defense Gene Responses in Pines. 26309284 5 41 theme Pro 1004:1006 arg1 residue 1008:1014 a Pro residue 1002:1014 a Pro residue at position 6 as well as O-glycosylation of Ser and Thr residues at positions 1 and 8 1002:1100 Posttranslational modifications included hydroxylation of a Pro residue at position 6 as well as O-glycosylation of Ser and Thr residues at positions 1 and 8, respectively. 26309284 5 41 theme Pro 1004:1006 arg1 Ser 1060:1062 Ser 1060:1062 Ser 1060:1062 Posttranslational modifications included hydroxylation of a Pro residue at position 6 as well as O-glycosylation of Ser and Thr residues at positions 1 and 8, respectively. 26309284 5 41 theme Pro 1004:1006 arg1 residues 1072:1079 Thr residues 1068:1079 Thr residues 1068:1079 Posttranslational modifications included hydroxylation of a Pro residue at position 6 as well as O-glycosylation of Ser and Thr residues at positions 1 and 8, respectively. 26309284 8 42 theme proline-rich 1545:1556 arg1 peptides 1572:1579 the O-glycosylated short-chain proline-rich antimicrobial peptides 1514:1579 the O-glycosylated short-chain proline-rich antimicrobial peptides exemplified by drosocin 1514:1603 This peptide, hereafter called noctilisin, is related to the O-glycosylated short-chain proline-rich antimicrobial peptides exemplified by drosocin. 26309284 4 43 theme 11-amino 738:745 arg1 acid 747:750 An 11-amino acid 735:750 An 11-amino acid 735:750 An 11-amino acid, posttranslationally modified peptide (SEGPROGTKRP) encoded by the most abundant transcript recovered from S. noctilio venom gland tissue comprised the backbone of the 1,850 Da active factor. 26309284 4 43 theme 11-amino 738:745 arg1 peptide 782:788 posttranslationally modified peptide 753:788 posttranslationally modified peptide (SEGPROGTKRP) encoded by the most abundant transcript recovered from S. noctilio venom gland tissue 753:888 An 11-amino acid, posttranslationally modified peptide (SEGPROGTKRP) encoded by the most abundant transcript recovered from S. noctilio venom gland tissue comprised the backbone of the 1,850 Da active factor. 26309284 5 44 theme Posttranslational 944:960 arg1 modifications 962:974 Posttranslational modifications 944:974 Posttranslational modifications 944:974 Posttranslational modifications included hydroxylation of a Pro residue at position 6 as well as O-glycosylation of Ser and Thr residues at positions 1 and 8, respectively. 26309284 5 45 gly O-glycosylation 1041:1055 arg1 positions 1084:1092 positions 1 and 8 1084:1100 positions 1 and 8 1084:1100 Posttranslational modifications included hydroxylation of a Pro residue at position 6 as well as O-glycosylation of Ser and Thr residues at positions 1 and 8, respectively. 26309284 5 45 gly O-glycosylation 1041:1055 arg1 position 1019:1026 position 6 1019:1028 position 6 1019:1028 Posttranslational modifications included hydroxylation of a Pro residue at position 6 as well as O-glycosylation of Ser and Thr residues at positions 1 and 8, respectively. 26309284 5 45 gly O-glycosylation 1041:1055 arg1 Ser 1060:1062 Ser 1060:1062 Ser 1060:1062 Posttranslational modifications included hydroxylation of a Pro residue at position 6 as well as O-glycosylation of Ser and Thr residues at positions 1 and 8, respectively. 26309284 5 45 gly O-glycosylation 1041:1055 arg2 positions 1084:1092 positions 1 and 8 1084:1100 positions 1 and 8 1084:1100 Posttranslational modifications included hydroxylation of a Pro residue at position 6 as well as O-glycosylation of Ser and Thr residues at positions 1 and 8, respectively. 26309284 5 45 gly O-glycosylation 1041:1055 arg1 residues 1072:1079 Thr residues 1068:1079 Thr residues 1068:1079 Posttranslational modifications included hydroxylation of a Pro residue at position 6 as well as O-glycosylation of Ser and Thr residues at positions 1 and 8, respectively. 26309284 5 45 gly O-glycosylation 1041:1055 arg2 position 1019:1026 position 6 1019:1028 position 6 1019:1028 Posttranslational modifications included hydroxylation of a Pro residue at position 6 as well as O-glycosylation of Ser and Thr residues at positions 1 and 8, respectively. 26309284 3 46 theme activity 627:634 arg1 assays 636:641 activity assays 627:641 activity assays based on defense gene induction as well as the needle wilt response in pine shoot explants 627:732 A heat-stable factor that can migrate from the site of oviposition in the trunk through the xylem to needles in the crown of attacked pines was purified by size-fractionation and reversed-phase-high-performance liquid chromatography using activity assays based on defense gene induction as well as the needle wilt response in pine shoot explants. 26309284 2 47 theme physiological 299:311 arg1 changes 313:319 host physiological changes 294:319 host physiological changes that facilitate subsequent lethal infection by a symbiotic fungus 294:385 The secretion induces a variety of host physiological changes that facilitate subsequent lethal infection by a symbiotic fungus. 26309284 7 48 theme excised 1441:1447 arg1 shoots 1449:1454 excised shoots 1441:1454 excised shoots 1441:1454 In contrast to the native peptide, a synthetic version of the hydroxylated peptide backbone lacking the glycosyl side chains failed to induce pine defense genes or cause needle wilt in excised shoots. 26309284 3 49 theme defense 652:658 arg1 induction 665:673 defense gene induction 652:673 defense gene induction as well as the needle wilt response in pine shoot explants 652:732 A heat-stable factor that can migrate from the site of oviposition in the trunk through the xylem to needles in the crown of attacked pines was purified by size-fractionation and reversed-phase-high-performance liquid chromatography using activity assays based on defense gene induction as well as the needle wilt response in pine shoot explants. 26309284 6 50 theme phosphoethanolamine 1235:1253 arg1 addition 1223:1230 addition 1223:1230 addition of phosphoethanolamine 1223:1253 The O-linked sugars were identical α-linked N-acetylgalactosamine residues modified at the C6 position by addition of phosphoethanolamine. 26309284 4 51 theme abundant 824:831 arg1 transcript 833:842 the most abundant transcript 815:842 the most abundant transcript recovered from S. noctilio venom gland tissue 815:888 An 11-amino acid, posttranslationally modified peptide (SEGPROGTKRP) encoded by the most abundant transcript recovered from S. noctilio venom gland tissue comprised the backbone of the 1,850 Da active factor. 26309284 6 52 theme O-linked 1121:1128 arg1 residues 1183:1190 identical α-linked N-acetylgalactosamine residues 1142:1190 identical α-linked N-acetylgalactosamine residues modified at the C6 position by addition of phosphoethanolamine 1142:1253 The O-linked sugars were identical α-linked N-acetylgalactosamine residues modified at the C6 position by addition of phosphoethanolamine. 26309284 6 52 theme O-linked 1121:1128 arg1 sugars 1130:1135 The O-linked sugars 1117:1135 The O-linked sugars 1117:1135 The O-linked sugars were identical α-linked N-acetylgalactosamine residues modified at the C6 position by addition of phosphoethanolamine. 26309284 3 53 from site 435:438 arg1 trunk 462:466 the trunk 458:466 the trunk 458:466 A heat-stable factor that can migrate from the site of oviposition in the trunk through the xylem to needles in the crown of attacked pines was purified by size-fractionation and reversed-phase-high-performance liquid chromatography using activity assays based on defense gene induction as well as the needle wilt response in pine shoot explants. 26309284 1 54 theme Sirex 160:164 arg1 noctilio 166:173 female Sirex noctilio 153:173 female Sirex noctilio (F.) (Siricidae) 153:190 During oviposition, female Sirex noctilio (F.) (Siricidae) woodwasps inject their conifer hosts with a venom gland secretion. 26309284 1 54 theme Sirex 160:164 arg1 Siricidae 181:189 Siricidae 181:189 Siricidae 181:189 During oviposition, female Sirex noctilio (F.) (Siricidae) woodwasps inject their conifer hosts with a venom gland secretion. 26309284 4 55 theme venom 871:875 arg1 tissue 883:888 S. noctilio venom gland tissue 859:888 S. noctilio venom gland tissue 859:888 An 11-amino acid, posttranslationally modified peptide (SEGPROGTKRP) encoded by the most abundant transcript recovered from S. noctilio venom gland tissue comprised the backbone of the 1,850 Da active factor. 26309284 7 56 theme side 1369:1372 arg1 chains 1374:1379 the glycosyl side chains 1356:1379 the glycosyl side chains 1356:1379 In contrast to the native peptide, a synthetic version of the hydroxylated peptide backbone lacking the glycosyl side chains failed to induce pine defense genes or cause needle wilt in excised shoots. 26309284 3 57 theme wilt 697:700 arg1 response 702:709 the needle wilt response 686:709 defense gene induction as well as the needle wilt response in pine shoot explants 652:732 A heat-stable factor that can migrate from the site of oviposition in the trunk through the xylem to needles in the crown of attacked pines was purified by size-fractionation and reversed-phase-high-performance liquid chromatography using activity assays based on defense gene induction as well as the needle wilt response in pine shoot explants. 26309284 0 58 theme Gene 108:111 arg1 Responses 113:121 Defense Gene Responses 100:121 Defense Gene Responses 100:121 Noctilisin, a Venom Glycopeptide of Sirex noctilio (Hymenoptera: Siricidae), Causes Needle Wilt and Defense Gene Responses in Pines. 26309284 3 59 theme attacked 513:520 arg1 pines 522:526 attacked pines 513:526 attacked pines 513:526 A heat-stable factor that can migrate from the site of oviposition in the trunk through the xylem to needles in the crown of attacked pines was purified by size-fractionation and reversed-phase-high-performance liquid chromatography using activity assays based on defense gene induction as well as the needle wilt response in pine shoot explants. 26309284 9 60 theme defense 1697:1703 arg1 systems 1705:1711 pine defense systems 1692:1711 pine defense systems 1692:1711 The noctilisin structure contains motifs which may explain how it avoids detection by pine defense systems. 26309284 5 61 theme O-glycosylation 1041:1055 arg1 hydroxylation 985:997 hydroxylation 985:997 hydroxylation of a Pro residue at position 6 as well as O-glycosylation of Ser and Thr residues at positions 1 and 8 985:1100 Posttranslational modifications included hydroxylation of a Pro residue at position 6 as well as O-glycosylation of Ser and Thr residues at positions 1 and 8, respectively. 26309284 7 62 theme backbone 1339:1346 arg1 version 1303:1309 a synthetic version 1291:1309 a synthetic version of the hydroxylated peptide backbone lacking the glycosyl side chains 1291:1379 In contrast to the native peptide, a synthetic version of the hydroxylated peptide backbone lacking the glycosyl side chains failed to induce pine defense genes or cause needle wilt in excised shoots. 26309284 6 63 link α-linked 1152:1159 arg1 residues 1183:1190 identical α-linked N-acetylgalactosamine residues 1142:1190 identical α-linked N-acetylgalactosamine residues modified at the C6 position by addition of phosphoethanolamine 1142:1253 The O-linked sugars were identical α-linked N-acetylgalactosamine residues modified at the C6 position by addition of phosphoethanolamine. 26309284 6 63 link α-linked 1152:1159 arg1 sugars 1130:1135 The O-linked sugars 1117:1135 The O-linked sugars 1117:1135 The O-linked sugars were identical α-linked N-acetylgalactosamine residues modified at the C6 position by addition of phosphoethanolamine. 26309284 4 64 theme S. 859:860 arg1 tissue 883:888 S. noctilio venom gland tissue 859:888 S. noctilio venom gland tissue 859:888 An 11-amino acid, posttranslationally modified peptide (SEGPROGTKRP) encoded by the most abundant transcript recovered from S. noctilio venom gland tissue comprised the backbone of the 1,850 Da active factor. 26309284 6 65 theme α-linked 1152:1159 arg1 residues 1183:1190 identical α-linked N-acetylgalactosamine residues 1142:1190 identical α-linked N-acetylgalactosamine residues modified at the C6 position by addition of phosphoethanolamine 1142:1253 The O-linked sugars were identical α-linked N-acetylgalactosamine residues modified at the C6 position by addition of phosphoethanolamine. 26309284 6 65 theme α-linked 1152:1159 arg1 sugars 1130:1135 The O-linked sugars 1117:1135 The O-linked sugars 1117:1135 The O-linked sugars were identical α-linked N-acetylgalactosamine residues modified at the C6 position by addition of phosphoethanolamine. 26309284 5 66 from position 1019:1026 arg1 residues 1072:1079 Thr residues 1068:1079 Thr residues 1068:1079 Posttranslational modifications included hydroxylation of a Pro residue at position 6 as well as O-glycosylation of Ser and Thr residues at positions 1 and 8, respectively. 26309284 5 66 from position 1019:1026 arg1 residue 1008:1014 a Pro residue 1002:1014 a Pro residue at position 6 as well as O-glycosylation of Ser and Thr residues at positions 1 and 8 1002:1100 Posttranslational modifications included hydroxylation of a Pro residue at position 6 as well as O-glycosylation of Ser and Thr residues at positions 1 and 8, respectively. 26309284 5 66 from position 1019:1026 arg1 Ser 1060:1062 Ser 1060:1062 Ser 1060:1062 Posttranslational modifications included hydroxylation of a Pro residue at position 6 as well as O-glycosylation of Ser and Thr residues at positions 1 and 8, respectively. 26309284 5 66 from position 1019:1026 arg1 hydroxylation 985:997 hydroxylation 985:997 hydroxylation of a Pro residue at position 6 as well as O-glycosylation of Ser and Thr residues at positions 1 and 8 985:1100 Posttranslational modifications included hydroxylation of a Pro residue at position 6 as well as O-glycosylation of Ser and Thr residues at positions 1 and 8, respectively. 26309284 5 66 from position 1019:1026 arg1 O-glycosylation 1041:1055 O-glycosylation 1041:1055 a Pro residue at position 6 as well as O-glycosylation of Ser and Thr residues at positions 1 and 8 1002:1100 Posttranslational modifications included hydroxylation of a Pro residue at position 6 as well as O-glycosylation of Ser and Thr residues at positions 1 and 8, respectively. 26309284 4 67 theme 1,850 920:924 arg1 factor 936:941 the 1,850 Da active factor 916:941 the 1,850 Da active factor 916:941 An 11-amino acid, posttranslationally modified peptide (SEGPROGTKRP) encoded by the most abundant transcript recovered from S. noctilio venom gland tissue comprised the backbone of the 1,850 Da active factor. 26309284 6 68 link O-linked 1121:1128 arg1 residues 1183:1190 identical α-linked N-acetylgalactosamine residues 1142:1190 identical α-linked N-acetylgalactosamine residues modified at the C6 position by addition of phosphoethanolamine 1142:1253 The O-linked sugars were identical α-linked N-acetylgalactosamine residues modified at the C6 position by addition of phosphoethanolamine. 26309284 6 68 link O-linked 1121:1128 arg1 sugars 1130:1135 The O-linked sugars 1117:1135 The O-linked sugars 1117:1135 The O-linked sugars were identical α-linked N-acetylgalactosamine residues modified at the C6 position by addition of phosphoethanolamine. 26309284 4 69 theme active 929:934 arg1 factor 936:941 the 1,850 Da active factor 916:941 the 1,850 Da active factor 916:941 An 11-amino acid, posttranslationally modified peptide (SEGPROGTKRP) encoded by the most abundant transcript recovered from S. noctilio venom gland tissue comprised the backbone of the 1,850 Da active factor. 26309284 8 70 theme called 1481:1486 arg1 peptide 1462:1468 This peptide 1457:1468 This peptide 1457:1468 This peptide, hereafter called noctilisin, is related to the O-glycosylated short-chain proline-rich antimicrobial peptides exemplified by drosocin. 26309284 8 70 theme called 1481:1486 arg1 noctilisin 1488:1497 hereafter called noctilisin 1471:1497 hereafter called noctilisin 1471:1497 This peptide, hereafter called noctilisin, is related to the O-glycosylated short-chain proline-rich antimicrobial peptides exemplified by drosocin. 26309284 0 71 theme Needle 84:89 arg1 Wilt 91:94 Needle Wilt 84:94 Needle Wilt 84:94 Noctilisin, a Venom Glycopeptide of Sirex noctilio (Hymenoptera: Siricidae), Causes Needle Wilt and Defense Gene Responses in Pines. 26309284 5 72 theme Ser 1060:1062 arg1 residue 1008:1014 a Pro residue 1002:1014 a Pro residue at position 6 as well as O-glycosylation of Ser and Thr residues at positions 1 and 8 1002:1100 Posttranslational modifications included hydroxylation of a Pro residue at position 6 as well as O-glycosylation of Ser and Thr residues at positions 1 and 8, respectively. 26309284 5 72 theme Ser 1060:1062 arg1 Ser 1060:1062 Ser 1060:1062 Ser 1060:1062 Posttranslational modifications included hydroxylation of a Pro residue at position 6 as well as O-glycosylation of Ser and Thr residues at positions 1 and 8, respectively. 26309284 5 72 theme Ser 1060:1062 arg1 residues 1072:1079 Thr residues 1068:1079 Thr residues 1068:1079 Posttranslational modifications included hydroxylation of a Pro residue at position 6 as well as O-glycosylation of Ser and Thr residues at positions 1 and 8, respectively. 26309284 5 72 theme Ser 1060:1062 arg1 O-glycosylation 1041:1055 O-glycosylation 1041:1055 a Pro residue at position 6 as well as O-glycosylation of Ser and Thr residues at positions 1 and 8 1002:1100 Posttranslational modifications included hydroxylation of a Pro residue at position 6 as well as O-glycosylation of Ser and Thr residues at positions 1 and 8, respectively. 26309284 5 73 theme Thr 1068:1070 arg1 residues 1072:1079 Thr residues 1068:1079 Thr residues 1068:1079 Posttranslational modifications included hydroxylation of a Pro residue at position 6 as well as O-glycosylation of Ser and Thr residues at positions 1 and 8, respectively. 26309284 8 74 gly O-glycosylated 1518:1531 arg1 peptides 1572:1579 the O-glycosylated short-chain proline-rich antimicrobial peptides 1514:1579 the O-glycosylated short-chain proline-rich antimicrobial peptides exemplified by drosocin 1514:1603 This peptide, hereafter called noctilisin, is related to the O-glycosylated short-chain proline-rich antimicrobial peptides exemplified by drosocin. 26309284 2 75 theme changes 313:319 arg1 changes 313:319 host physiological changes 294:319 host physiological changes that facilitate subsequent lethal infection by a symbiotic fungus 294:385 The secretion induces a variety of host physiological changes that facilitate subsequent lethal infection by a symbiotic fungus. 26309284 2 75 theme changes 313:319 arg1 variety 283:289 a variety 281:289 a variety of host physiological changes that facilitate subsequent lethal infection by a symbiotic fungus 281:385 The secretion induces a variety of host physiological changes that facilitate subsequent lethal infection by a symbiotic fungus. 26309284 0 76 theme Venom 14:18 arg1 Noctilisin 0:9 Noctilisin 0:9 Noctilisin 0:9 Noctilisin, a Venom Glycopeptide of Sirex noctilio (Hymenoptera: Siricidae), Causes Needle Wilt and Defense Gene Responses in Pines. 26309284 0 76 theme Venom 14:18 arg1 Glycopeptide 20:31 a Venom Glycopeptide 12:31 a Venom Glycopeptide of Sirex noctilio (Hymenoptera: Siricidae) 12:74 Noctilisin, a Venom Glycopeptide of Sirex noctilio (Hymenoptera: Siricidae), Causes Needle Wilt and Defense Gene Responses in Pines. 26309284 0 77 dep Hymenoptera 52:62 arg1 Siricidae 65:73 Siricidae 65:73 Siricidae 65:73 Noctilisin, a Venom Glycopeptide of Sirex noctilio (Hymenoptera: Siricidae), Causes Needle Wilt and Defense Gene Responses in Pines. 26309284 2 78 theme symbiotic 370:378 arg1 fungus 380:385 a symbiotic fungus 368:385 a symbiotic fungus 368:385 The secretion induces a variety of host physiological changes that facilitate subsequent lethal infection by a symbiotic fungus. 26309284 3 79 theme liquid 599:604 arg1 chromatography 606:619 size-fractionation and reversed-phase-high-performance liquid chromatography 544:619 size-fractionation and reversed-phase-high-performance liquid chromatography 544:619 A heat-stable factor that can migrate from the site of oviposition in the trunk through the xylem to needles in the crown of attacked pines was purified by size-fractionation and reversed-phase-high-performance liquid chromatography using activity assays based on defense gene induction as well as the needle wilt response in pine shoot explants. 26309284 5 80 from positions 1084:1092 arg1 residues 1072:1079 Thr residues 1068:1079 Thr residues 1068:1079 Posttranslational modifications included hydroxylation of a Pro residue at position 6 as well as O-glycosylation of Ser and Thr residues at positions 1 and 8, respectively. 26309284 5 80 from positions 1084:1092 arg1 residue 1008:1014 a Pro residue 1002:1014 a Pro residue at position 6 as well as O-glycosylation of Ser and Thr residues at positions 1 and 8 1002:1100 Posttranslational modifications included hydroxylation of a Pro residue at position 6 as well as O-glycosylation of Ser and Thr residues at positions 1 and 8, respectively. 26309284 5 80 from positions 1084:1092 arg1 Ser 1060:1062 Ser 1060:1062 Ser 1060:1062 Posttranslational modifications included hydroxylation of a Pro residue at position 6 as well as O-glycosylation of Ser and Thr residues at positions 1 and 8, respectively. 26309284 5 80 from positions 1084:1092 arg1 hydroxylation 985:997 hydroxylation 985:997 hydroxylation of a Pro residue at position 6 as well as O-glycosylation of Ser and Thr residues at positions 1 and 8 985:1100 Posttranslational modifications included hydroxylation of a Pro residue at position 6 as well as O-glycosylation of Ser and Thr residues at positions 1 and 8, respectively. 26309284 5 80 from positions 1084:1092 arg1 O-glycosylation 1041:1055 O-glycosylation 1041:1055 a Pro residue at position 6 as well as O-glycosylation of Ser and Thr residues at positions 1 and 8 1002:1100 Posttranslational modifications included hydroxylation of a Pro residue at position 6 as well as O-glycosylation of Ser and Thr residues at positions 1 and 8, respectively. 26309284 0 81 dep noctilio 42:49 arg1 Hymenoptera 52:62 Hymenoptera 52:62 Hymenoptera 52:62 Noctilisin, a Venom Glycopeptide of Sirex noctilio (Hymenoptera: Siricidae), Causes Needle Wilt and Defense Gene Responses in Pines. 26309284 8 82 theme short-chain 1533:1543 arg1 peptides 1572:1579 the O-glycosylated short-chain proline-rich antimicrobial peptides 1514:1579 the O-glycosylated short-chain proline-rich antimicrobial peptides exemplified by drosocin 1514:1603 This peptide, hereafter called noctilisin, is related to the O-glycosylated short-chain proline-rich antimicrobial peptides exemplified by drosocin. 26309284 2 83 theme lethal 348:353 arg1 infection 355:363 subsequent lethal infection 337:363 subsequent lethal infection 337:363 The secretion induces a variety of host physiological changes that facilitate subsequent lethal infection by a symbiotic fungus. 26309284 0 84 theme noctilio 42:49 arg1 Noctilisin 0:9 Noctilisin 0:9 Noctilisin 0:9 Noctilisin, a Venom Glycopeptide of Sirex noctilio (Hymenoptera: Siricidae), Causes Needle Wilt and Defense Gene Responses in Pines. 26309284 0 84 theme noctilio 42:49 arg1 Glycopeptide 20:31 a Venom Glycopeptide 12:31 a Venom Glycopeptide of Sirex noctilio (Hymenoptera: Siricidae) 12:74 Noctilisin, a Venom Glycopeptide of Sirex noctilio (Hymenoptera: Siricidae), Causes Needle Wilt and Defense Gene Responses in Pines. 26309284 1 85 theme gland 242:246 arg1 secretion 248:256 a venom gland secretion 234:256 a venom gland secretion 234:256 During oviposition, female Sirex noctilio (F.) (Siricidae) woodwasps inject their conifer hosts with a venom gland secretion. 26309284 8 86 theme antimicrobial 1558:1570 arg1 peptides 1572:1579 the O-glycosylated short-chain proline-rich antimicrobial peptides 1514:1579 the O-glycosylated short-chain proline-rich antimicrobial peptides exemplified by drosocin 1514:1603 This peptide, hereafter called noctilisin, is related to the O-glycosylated short-chain proline-rich antimicrobial peptides exemplified by drosocin. 26309284 9 87 theme noctilisin 1610:1619 arg1 structure 1621:1629 The noctilisin structure 1606:1629 The noctilisin structure 1606:1629 The noctilisin structure contains motifs which may explain how it avoids detection by pine defense systems. 26309284 3 88 theme gene 660:663 arg1 induction 665:673 defense gene induction 652:673 defense gene induction as well as the needle wilt response in pine shoot explants 652:732 A heat-stable factor that can migrate from the site of oviposition in the trunk through the xylem to needles in the crown of attacked pines was purified by size-fractionation and reversed-phase-high-performance liquid chromatography using activity assays based on defense gene induction as well as the needle wilt response in pine shoot explants. 26309284 1 89 dep noctilio 166:173 arg1 F 176:176 F 176:176 F. 176:177 During oviposition, female Sirex noctilio (F.) (Siricidae) woodwasps inject their conifer hosts with a venom gland secretion. 26309284 2 90 theme host 294:297 arg1 changes 313:319 host physiological changes 294:319 host physiological changes that facilitate subsequent lethal infection by a symbiotic fungus 294:385 The secretion induces a variety of host physiological changes that facilitate subsequent lethal infection by a symbiotic fungus. 25918883 7 0 theme hosts 1383:1387 arg1 capabilities 1361:1372 the capabilities 1357:1372 the capabilities of these hosts to act as cell factories 1357:1412 To further investigate the capabilities of these hosts to act as cell factories, we examined the glycosylation pathway gene expression profiles as well as the levels of endoplasmic reticulum (ER) and mitochondria in the untransfected hosts. 25918883 4 1 link derived 640:646 arg1 lines 658:662 clonally derived host cell lines 631:662 clonally derived host cell lines isolated from CHOK1SV for the ability to manufacture two model proteins, an IgG4 monoclonal antibody (Mab) and an Fc-fusion protein (etanercept) 631:807 In this work, we examine a panel of clonally derived host cell lines isolated from CHOK1SV for the ability to manufacture two model proteins, an IgG4 monoclonal antibody (Mab) and an Fc-fusion protein (etanercept). 25918883 9 2 theme CHOK1SV 1783:1789 arg1 pool 1791:1794 the CHOK1SV pool 1779:1794 the CHOK1SV pool 1779:1794 This work demonstrates the utility of leveraging diversity within the CHOK1SV pool to identify new host cell lines with different performance characteristics. 25918883 4 3 theme monoclonal 745:754 arg1 antibody 756:763 an IgG4 monoclonal antibody 737:763 an IgG4 monoclonal antibody (Mab) 737:769 In this work, we examine a panel of clonally derived host cell lines isolated from CHOK1SV for the ability to manufacture two model proteins, an IgG4 monoclonal antibody (Mab) and an Fc-fusion protein (etanercept). 25918883 4 3 theme monoclonal 745:754 arg1 Mab 766:768 Mab 766:768 Mab 766:768 In this work, we examine a panel of clonally derived host cell lines isolated from CHOK1SV for the ability to manufacture two model proteins, an IgG4 monoclonal antibody (Mab) and an Fc-fusion protein (etanercept). 25918883 6 4 theme tandem 1131:1136 arg1 LC-MS/MS 1157:1164 LC-MS/MS 1157:1164 LC-MS/MS 1157:1164 Furthermore, we examined the PQ attributes of the stable pool-produced Mab and etanercept (by N-glycan ultra performance liquid chromatography (UPLC) and liquid chromatography - tandem mass spectrometry (LC-MS/MS), respectively), and uncovered substantial variation between the host cell lines in Mab N-glycan micro-heterogeneity and etanercept N and O-linked macro-heterogeneity. 25918883 6 4 theme tandem 1131:1136 arg1 spectrometry 1143:1154 tandem mass spectrometry 1131:1154 tandem mass spectrometry (LC-MS/MS) 1131:1165 Furthermore, we examined the PQ attributes of the stable pool-produced Mab and etanercept (by N-glycan ultra performance liquid chromatography (UPLC) and liquid chromatography - tandem mass spectrometry (LC-MS/MS), respectively), and uncovered substantial variation between the host cell lines in Mab N-glycan micro-heterogeneity and etanercept N and O-linked macro-heterogeneity. 25918883 8 5 theme moderate 1590:1597 arg1 correlation 1599:1609 a moderate correlation 1588:1609 a moderate correlation between ER mass and the volumetric product concentration in transient and stable pool Mab production 1588:1710 We uncovered a moderate correlation between ER mass and the volumetric product concentration in transient and stable pool Mab production. 25918883 1 6 theme hamster 158:164 arg1 ovary 166:170 individual Chinese hamster ovary 139:170 individual Chinese hamster ovary (CHO) host cell lines 139:192 Much effort has been expended to improve the capabilities of individual Chinese hamster ovary (CHO) host cell lines to synthesize recombinant therapeutic proteins (rPs). 25918883 1 6 theme hamster 158:164 arg1 CHO 173:175 CHO 173:175 CHO 173:175 Much effort has been expended to improve the capabilities of individual Chinese hamster ovary (CHO) host cell lines to synthesize recombinant therapeutic proteins (rPs). 25918883 6 7 theme etanercept 1032:1041 arg1 attributes 985:994 the PQ attributes 978:994 the PQ attributes of the stable pool-produced Mab and etanercept (by N-glycan ultra performance liquid chromatography (UPLC) and liquid chromatography - tandem mass spectrometry (LC-MS/MS), respectively) 978:1180 Furthermore, we examined the PQ attributes of the stable pool-produced Mab and etanercept (by N-glycan ultra performance liquid chromatography (UPLC) and liquid chromatography - tandem mass spectrometry (LC-MS/MS), respectively), and uncovered substantial variation between the host cell lines in Mab N-glycan micro-heterogeneity and etanercept N and O-linked macro-heterogeneity. 25918883 9 8 theme new 1808:1810 arg1 lines 1822:1826 new host cell lines 1808:1826 new host cell lines with different performance characteristics 1808:1869 This work demonstrates the utility of leveraging diversity within the CHOK1SV pool to identify new host cell lines with different performance characteristics. 25918883 2 9 theme increasing 267:276 arg1 variety 278:284 the increasing variety 263:284 the increasing variety in rP molecular types and formats 263:318 However, given the increasing variety in rP molecular types and formats it may be advantageous to employ a toolbox of CHO host cell lines in biomanufacturing. 25918883 6 10 theme Mab 1024:1026 arg1 attributes 985:994 the PQ attributes 978:994 the PQ attributes of the stable pool-produced Mab and etanercept (by N-glycan ultra performance liquid chromatography (UPLC) and liquid chromatography - tandem mass spectrometry (LC-MS/MS), respectively) 978:1180 Furthermore, we examined the PQ attributes of the stable pool-produced Mab and etanercept (by N-glycan ultra performance liquid chromatography (UPLC) and liquid chromatography - tandem mass spectrometry (LC-MS/MS), respectively), and uncovered substantial variation between the host cell lines in Mab N-glycan micro-heterogeneity and etanercept N and O-linked macro-heterogeneity. 25918883 9 11 theme cell 1817:1820 arg1 lines 1822:1826 new host cell lines 1808:1826 new host cell lines with different performance characteristics 1808:1869 This work demonstrates the utility of leveraging diversity within the CHOK1SV pool to identify new host cell lines with different performance characteristics. 25918883 6 12 theme substantial 1197:1207 arg1 variation 1209:1217 substantial variation 1197:1217 substantial variation between the host cell lines in Mab N-glycan micro-heterogeneity and etanercept N and O-linked macro-heterogeneity 1197:1331 Furthermore, we examined the PQ attributes of the stable pool-produced Mab and etanercept (by N-glycan ultra performance liquid chromatography (UPLC) and liquid chromatography - tandem mass spectrometry (LC-MS/MS), respectively), and uncovered substantial variation between the host cell lines in Mab N-glycan micro-heterogeneity and etanercept N and O-linked macro-heterogeneity. 25918883 3 13 theme molecular 502:510 arg1 types 512:516 certain molecular types 494:516 certain molecular types 494:516 Such a toolbox would contain a panel of hosts with specific capabilities to synthesize certain molecular types at high volumetric concentrations and with the correct product quality (PQ). 25918883 7 14 theme reticulum 1515:1523 arg1 levels 1493:1498 the levels 1489:1498 the glycosylation pathway gene expression profiles as well as the levels of endoplasmic reticulum (ER) and mitochondria in the untransfected hosts 1427:1572 To further investigate the capabilities of these hosts to act as cell factories, we examined the glycosylation pathway gene expression profiles as well as the levels of endoplasmic reticulum (ER) and mitochondria in the untransfected hosts. 25918883 7 14 theme reticulum 1515:1523 arg1 profiles 1469:1476 the glycosylation pathway gene expression profiles 1427:1476 the glycosylation pathway gene expression profiles as well as the levels of endoplasmic reticulum (ER) and mitochondria in the untransfected hosts 1427:1572 To further investigate the capabilities of these hosts to act as cell factories, we examined the glycosylation pathway gene expression profiles as well as the levels of endoplasmic reticulum (ER) and mitochondria in the untransfected hosts. 25918883 6 15 theme liquid 1107:1112 arg1 chromatography 1114:1127 liquid chromatography 1107:1127 liquid chromatography 1107:1127 Furthermore, we examined the PQ attributes of the stable pool-produced Mab and etanercept (by N-glycan ultra performance liquid chromatography (UPLC) and liquid chromatography - tandem mass spectrometry (LC-MS/MS), respectively), and uncovered substantial variation between the host cell lines in Mab N-glycan micro-heterogeneity and etanercept N and O-linked macro-heterogeneity. 25918883 3 16 theme product 573:579 arg1 PQ 590:591 PQ 590:591 PQ 590:591 Such a toolbox would contain a panel of hosts with specific capabilities to synthesize certain molecular types at high volumetric concentrations and with the correct product quality (PQ). 25918883 3 16 theme product 573:579 arg1 quality 581:587 the correct product quality 561:587 the correct product quality (PQ) 561:592 Such a toolbox would contain a panel of hosts with specific capabilities to synthesize certain molecular types at high volumetric concentrations and with the correct product quality (PQ). 25918883 0 17 theme clone 18:22 arg1 performance 24:34 host clone performance 13:34 host clone performance 13:34 Diversity in host clone performance within a Chinese hamster ovary cell line. 25918883 1 18 theme cell 183:186 arg1 lines 188:192 individual Chinese hamster ovary (CHO) host cell lines 139:192 individual Chinese hamster ovary (CHO) host cell lines 139:192 Much effort has been expended to improve the capabilities of individual Chinese hamster ovary (CHO) host cell lines to synthesize recombinant therapeutic proteins (rPs). 25918883 9 19 theme performance 1843:1853 arg1 characteristics 1855:1869 different performance characteristics 1833:1869 different performance characteristics 1833:1869 This work demonstrates the utility of leveraging diversity within the CHOK1SV pool to identify new host cell lines with different performance characteristics. 25918883 3 20 theme volumetric 526:535 arg1 concentrations 537:550 high volumetric concentrations 521:550 high volumetric concentrations 521:550 Such a toolbox would contain a panel of hosts with specific capabilities to synthesize certain molecular types at high volumetric concentrations and with the correct product quality (PQ). 25918883 8 21 theme product 1646:1652 arg1 concentration 1654:1666 the volumetric product concentration 1631:1666 the volumetric product concentration in transient and stable pool Mab production 1631:1710 We uncovered a moderate correlation between ER mass and the volumetric product concentration in transient and stable pool Mab production. 25918883 4 22 theme derived 640:646 arg1 lines 658:662 clonally derived host cell lines 631:662 clonally derived host cell lines isolated from CHOK1SV for the ability to manufacture two model proteins, an IgG4 monoclonal antibody (Mab) and an Fc-fusion protein (etanercept) 631:807 In this work, we examine a panel of clonally derived host cell lines isolated from CHOK1SV for the ability to manufacture two model proteins, an IgG4 monoclonal antibody (Mab) and an Fc-fusion protein (etanercept). 25918883 5 23 theme pool 929:932 arg1 format 945:950 transient and stable pool production format 908:950 transient and stable pool production format 908:950 We show that these host cell lines vary in their relative ability to synthesize these proteins in transient and stable pool production format. 25918883 6 24 theme ultra 1056:1060 arg1 chromatography 1081:1094 N-glycan ultra performance liquid chromatography 1047:1094 N-glycan ultra performance liquid chromatography (UPLC) 1047:1101 Furthermore, we examined the PQ attributes of the stable pool-produced Mab and etanercept (by N-glycan ultra performance liquid chromatography (UPLC) and liquid chromatography - tandem mass spectrometry (LC-MS/MS), respectively), and uncovered substantial variation between the host cell lines in Mab N-glycan micro-heterogeneity and etanercept N and O-linked macro-heterogeneity. 25918883 6 24 theme ultra 1056:1060 arg1 UPLC 1097:1100 UPLC 1097:1100 UPLC 1097:1100 Furthermore, we examined the PQ attributes of the stable pool-produced Mab and etanercept (by N-glycan ultra performance liquid chromatography (UPLC) and liquid chromatography - tandem mass spectrometry (LC-MS/MS), respectively), and uncovered substantial variation between the host cell lines in Mab N-glycan micro-heterogeneity and etanercept N and O-linked macro-heterogeneity. 25918883 6 25 theme liquid 1074:1079 arg1 chromatography 1081:1094 N-glycan ultra performance liquid chromatography 1047:1094 N-glycan ultra performance liquid chromatography (UPLC) 1047:1101 Furthermore, we examined the PQ attributes of the stable pool-produced Mab and etanercept (by N-glycan ultra performance liquid chromatography (UPLC) and liquid chromatography - tandem mass spectrometry (LC-MS/MS), respectively), and uncovered substantial variation between the host cell lines in Mab N-glycan micro-heterogeneity and etanercept N and O-linked macro-heterogeneity. 25918883 6 25 theme liquid 1074:1079 arg1 UPLC 1097:1100 UPLC 1097:1100 UPLC 1097:1100 Furthermore, we examined the PQ attributes of the stable pool-produced Mab and etanercept (by N-glycan ultra performance liquid chromatography (UPLC) and liquid chromatography - tandem mass spectrometry (LC-MS/MS), respectively), and uncovered substantial variation between the host cell lines in Mab N-glycan micro-heterogeneity and etanercept N and O-linked macro-heterogeneity. 25918883 6 26 theme Mab 1250:1252 arg1 micro-heterogeneity 1263:1281 Mab N-glycan micro-heterogeneity 1250:1281 Mab N-glycan micro-heterogeneity 1250:1281 Furthermore, we examined the PQ attributes of the stable pool-produced Mab and etanercept (by N-glycan ultra performance liquid chromatography (UPLC) and liquid chromatography - tandem mass spectrometry (LC-MS/MS), respectively), and uncovered substantial variation between the host cell lines in Mab N-glycan micro-heterogeneity and etanercept N and O-linked macro-heterogeneity. 25918883 0 27 theme cell 67:70 arg1 line 72:75 a Chinese hamster ovary cell line 43:75 a Chinese hamster ovary cell line 43:75 Diversity in host clone performance within a Chinese hamster ovary cell line. 25918883 8 28 theme pool 1692:1695 arg1 production 1701:1710 transient and stable pool Mab production 1671:1710 transient and stable pool Mab production 1671:1710 We uncovered a moderate correlation between ER mass and the volumetric product concentration in transient and stable pool Mab production. 25918883 1 29 theme individual 139:148 arg1 ovary 166:170 individual Chinese hamster ovary 139:170 individual Chinese hamster ovary (CHO) host cell lines 139:192 Much effort has been expended to improve the capabilities of individual Chinese hamster ovary (CHO) host cell lines to synthesize recombinant therapeutic proteins (rPs). 25918883 1 29 theme individual 139:148 arg1 CHO 173:175 CHO 173:175 CHO 173:175 Much effort has been expended to improve the capabilities of individual Chinese hamster ovary (CHO) host cell lines to synthesize recombinant therapeutic proteins (rPs). 25918883 2 30 from variety 278:284 arg1 formats 312:318 formats 312:318 formats 312:318 However, given the increasing variety in rP molecular types and formats it may be advantageous to employ a toolbox of CHO host cell lines in biomanufacturing. 25918883 2 30 from variety 278:284 arg1 types 302:306 rP molecular types 289:306 rP molecular types 289:306 However, given the increasing variety in rP molecular types and formats it may be advantageous to employ a toolbox of CHO host cell lines in biomanufacturing. 25918883 7 31 theme gene 1453:1456 arg1 profiles 1469:1476 the glycosylation pathway gene expression profiles 1427:1476 the glycosylation pathway gene expression profiles as well as the levels of endoplasmic reticulum (ER) and mitochondria in the untransfected hosts 1427:1572 To further investigate the capabilities of these hosts to act as cell factories, we examined the glycosylation pathway gene expression profiles as well as the levels of endoplasmic reticulum (ER) and mitochondria in the untransfected hosts. 25918883 0 32 from Diversity 0:8 arg1 performance 24:34 host clone performance 13:34 host clone performance 13:34 Diversity in host clone performance within a Chinese hamster ovary cell line. 25918883 6 33 theme host 1231:1234 arg1 lines 1241:1245 the host cell lines 1227:1245 the host cell lines in Mab N-glycan micro-heterogeneity and etanercept N and O-linked macro-heterogeneity 1227:1331 Furthermore, we examined the PQ attributes of the stable pool-produced Mab and etanercept (by N-glycan ultra performance liquid chromatography (UPLC) and liquid chromatography - tandem mass spectrometry (LC-MS/MS), respectively), and uncovered substantial variation between the host cell lines in Mab N-glycan micro-heterogeneity and etanercept N and O-linked macro-heterogeneity. 25918883 7 34 theme glycosylation 1431:1443 arg1 profiles 1469:1476 the glycosylation pathway gene expression profiles 1427:1476 the glycosylation pathway gene expression profiles as well as the levels of endoplasmic reticulum (ER) and mitochondria in the untransfected hosts 1427:1572 To further investigate the capabilities of these hosts to act as cell factories, we examined the glycosylation pathway gene expression profiles as well as the levels of endoplasmic reticulum (ER) and mitochondria in the untransfected hosts. 25918883 3 35 contain contain 428:434 arg1 toolbox 414:420 Such a toolbox 407:420 Such a toolbox 407:420 Such a toolbox would contain a panel of hosts with specific capabilities to synthesize certain molecular types at high volumetric concentrations and with the correct product quality (PQ). 25918883 3 35 contain contain 428:434 arg2 panel 438:442 a panel 436:442 a panel of hosts with specific capabilities to synthesize certain molecular types at high volumetric concentrations and with the correct product quality (PQ) 436:592 Such a toolbox would contain a panel of hosts with specific capabilities to synthesize certain molecular types at high volumetric concentrations and with the correct product quality (PQ). 25918883 0 36 theme ovary 61:65 arg1 line 72:75 a Chinese hamster ovary cell line 43:75 a Chinese hamster ovary cell line 43:75 Diversity in host clone performance within a Chinese hamster ovary cell line. 25918883 4 37 theme cell 653:656 arg1 lines 658:662 clonally derived host cell lines 631:662 clonally derived host cell lines isolated from CHOK1SV for the ability to manufacture two model proteins, an IgG4 monoclonal antibody (Mab) and an Fc-fusion protein (etanercept) 631:807 In this work, we examine a panel of clonally derived host cell lines isolated from CHOK1SV for the ability to manufacture two model proteins, an IgG4 monoclonal antibody (Mab) and an Fc-fusion protein (etanercept). 25918883 1 38 theme Much 78:81 arg1 effort 83:88 Much effort 78:88 Much effort 78:88 Much effort has been expended to improve the capabilities of individual Chinese hamster ovary (CHO) host cell lines to synthesize recombinant therapeutic proteins (rPs). 25918883 7 39 theme mitochondria 1534:1545 arg1 levels 1493:1498 the levels 1489:1498 the glycosylation pathway gene expression profiles as well as the levels of endoplasmic reticulum (ER) and mitochondria in the untransfected hosts 1427:1572 To further investigate the capabilities of these hosts to act as cell factories, we examined the glycosylation pathway gene expression profiles as well as the levels of endoplasmic reticulum (ER) and mitochondria in the untransfected hosts. 25918883 7 39 theme mitochondria 1534:1545 arg1 profiles 1469:1476 the glycosylation pathway gene expression profiles 1427:1476 the glycosylation pathway gene expression profiles as well as the levels of endoplasmic reticulum (ER) and mitochondria in the untransfected hosts 1427:1572 To further investigate the capabilities of these hosts to act as cell factories, we examined the glycosylation pathway gene expression profiles as well as the levels of endoplasmic reticulum (ER) and mitochondria in the untransfected hosts. 25918883 2 40 theme cell 375:378 arg1 lines 380:384 CHO host cell lines 366:384 CHO host cell lines 366:384 However, given the increasing variety in rP molecular types and formats it may be advantageous to employ a toolbox of CHO host cell lines in biomanufacturing. 25918883 2 41 theme CHO 366:368 arg1 lines 380:384 CHO host cell lines 366:384 CHO host cell lines 366:384 However, given the increasing variety in rP molecular types and formats it may be advantageous to employ a toolbox of CHO host cell lines in biomanufacturing. 25918883 0 42 theme host 13:16 arg1 performance 24:34 host clone performance 13:34 host clone performance 13:34 Diversity in host clone performance within a Chinese hamster ovary cell line. 25918883 6 43 dep micro-heterogeneity 1263:1281 arg1 N 1298:1298 N 1298:1298 N 1298:1298 Furthermore, we examined the PQ attributes of the stable pool-produced Mab and etanercept (by N-glycan ultra performance liquid chromatography (UPLC) and liquid chromatography - tandem mass spectrometry (LC-MS/MS), respectively), and uncovered substantial variation between the host cell lines in Mab N-glycan micro-heterogeneity and etanercept N and O-linked macro-heterogeneity. 25918883 5 44 theme cell 834:837 arg1 lines 839:843 these host cell lines 823:843 these host cell lines 823:843 We show that these host cell lines vary in their relative ability to synthesize these proteins in transient and stable pool production format. 25918883 0 45 theme hamster 53:59 arg1 line 72:75 a Chinese hamster ovary cell line 43:75 a Chinese hamster ovary cell line 43:75 Diversity in host clone performance within a Chinese hamster ovary cell line. 25918883 7 46 from profiles 1469:1476 arg1 hosts 1568:1572 the untransfected hosts 1550:1572 the untransfected hosts 1550:1572 To further investigate the capabilities of these hosts to act as cell factories, we examined the glycosylation pathway gene expression profiles as well as the levels of endoplasmic reticulum (ER) and mitochondria in the untransfected hosts. 25918883 5 47 theme transient 908:916 arg1 format 945:950 transient and stable pool production format 908:950 transient and stable pool production format 908:950 We show that these host cell lines vary in their relative ability to synthesize these proteins in transient and stable pool production format. 25918883 8 48 from mass 1622:1625 arg1 production 1701:1710 transient and stable pool Mab production 1671:1710 transient and stable pool Mab production 1671:1710 We uncovered a moderate correlation between ER mass and the volumetric product concentration in transient and stable pool Mab production. 25918883 2 49 theme rP 289:290 arg1 types 302:306 rP molecular types 289:306 rP molecular types 289:306 However, given the increasing variety in rP molecular types and formats it may be advantageous to employ a toolbox of CHO host cell lines in biomanufacturing. 25918883 1 50 theme lines 188:192 arg1 capabilities 123:134 the capabilities 119:134 the capabilities of individual Chinese hamster ovary (CHO) host cell lines 119:192 Much effort has been expended to improve the capabilities of individual Chinese hamster ovary (CHO) host cell lines to synthesize recombinant therapeutic proteins (rPs). 25918883 2 51 from toolbox 355:361 arg1 biomanufacturing 389:404 biomanufacturing 389:404 biomanufacturing 389:404 However, given the increasing variety in rP molecular types and formats it may be advantageous to employ a toolbox of CHO host cell lines in biomanufacturing. 25918883 3 52 theme hosts 447:451 arg1 panel 438:442 a panel 436:442 a panel of hosts with specific capabilities to synthesize certain molecular types at high volumetric concentrations and with the correct product quality (PQ) 436:592 Such a toolbox would contain a panel of hosts with specific capabilities to synthesize certain molecular types at high volumetric concentrations and with the correct product quality (PQ). 25918883 9 53 theme diversity 1762:1770 arg1 utility 1740:1746 the utility 1736:1746 the utility of leveraging diversity within the CHOK1SV pool 1736:1794 This work demonstrates the utility of leveraging diversity within the CHOK1SV pool to identify new host cell lines with different performance characteristics. 25918883 1 54 theme therapeutic 220:230 arg1 proteins 232:239 recombinant therapeutic proteins 208:239 recombinant therapeutic proteins (rPs) 208:245 Much effort has been expended to improve the capabilities of individual Chinese hamster ovary (CHO) host cell lines to synthesize recombinant therapeutic proteins (rPs). 25918883 1 54 theme therapeutic 220:230 arg1 rPs 242:244 rPs 242:244 rPs 242:244 Much effort has been expended to improve the capabilities of individual Chinese hamster ovary (CHO) host cell lines to synthesize recombinant therapeutic proteins (rPs). 25918883 3 55 with hosts 447:451 arg1 capabilities 467:478 specific capabilities 458:478 specific capabilities 458:478 Such a toolbox would contain a panel of hosts with specific capabilities to synthesize certain molecular types at high volumetric concentrations and with the correct product quality (PQ). 25918883 7 56 gly glycosylation 1431:1443 arg1 mitochondria 1534:1545 mitochondria 1534:1545 mitochondria 1534:1545 To further investigate the capabilities of these hosts to act as cell factories, we examined the glycosylation pathway gene expression profiles as well as the levels of endoplasmic reticulum (ER) and mitochondria in the untransfected hosts. 25918883 7 56 gly glycosylation 1431:1443 arg1 reticulum 1515:1523 endoplasmic reticulum 1503:1523 endoplasmic reticulum (ER) 1503:1528 To further investigate the capabilities of these hosts to act as cell factories, we examined the glycosylation pathway gene expression profiles as well as the levels of endoplasmic reticulum (ER) and mitochondria in the untransfected hosts. 25918883 7 56 gly glycosylation 1431:1443 arg1 ER 1526:1527 ER 1526:1527 ER 1526:1527 To further investigate the capabilities of these hosts to act as cell factories, we examined the glycosylation pathway gene expression profiles as well as the levels of endoplasmic reticulum (ER) and mitochondria in the untransfected hosts. 25918883 6 57 theme N-glycan 1047:1054 arg1 chromatography 1081:1094 N-glycan ultra performance liquid chromatography 1047:1094 N-glycan ultra performance liquid chromatography (UPLC) 1047:1101 Furthermore, we examined the PQ attributes of the stable pool-produced Mab and etanercept (by N-glycan ultra performance liquid chromatography (UPLC) and liquid chromatography - tandem mass spectrometry (LC-MS/MS), respectively), and uncovered substantial variation between the host cell lines in Mab N-glycan micro-heterogeneity and etanercept N and O-linked macro-heterogeneity. 25918883 6 57 theme N-glycan 1047:1054 arg1 UPLC 1097:1100 UPLC 1097:1100 UPLC 1097:1100 Furthermore, we examined the PQ attributes of the stable pool-produced Mab and etanercept (by N-glycan ultra performance liquid chromatography (UPLC) and liquid chromatography - tandem mass spectrometry (LC-MS/MS), respectively), and uncovered substantial variation between the host cell lines in Mab N-glycan micro-heterogeneity and etanercept N and O-linked macro-heterogeneity. 25918883 6 58 theme mass 1138:1141 arg1 LC-MS/MS 1157:1164 LC-MS/MS 1157:1164 LC-MS/MS 1157:1164 Furthermore, we examined the PQ attributes of the stable pool-produced Mab and etanercept (by N-glycan ultra performance liquid chromatography (UPLC) and liquid chromatography - tandem mass spectrometry (LC-MS/MS), respectively), and uncovered substantial variation between the host cell lines in Mab N-glycan micro-heterogeneity and etanercept N and O-linked macro-heterogeneity. 25918883 6 58 theme mass 1138:1141 arg1 spectrometry 1143:1154 tandem mass spectrometry 1131:1154 tandem mass spectrometry (LC-MS/MS) 1131:1165 Furthermore, we examined the PQ attributes of the stable pool-produced Mab and etanercept (by N-glycan ultra performance liquid chromatography (UPLC) and liquid chromatography - tandem mass spectrometry (LC-MS/MS), respectively), and uncovered substantial variation between the host cell lines in Mab N-glycan micro-heterogeneity and etanercept N and O-linked macro-heterogeneity. 25918883 3 59 theme specific 458:465 arg1 capabilities 467:478 specific capabilities 458:478 specific capabilities 458:478 Such a toolbox would contain a panel of hosts with specific capabilities to synthesize certain molecular types at high volumetric concentrations and with the correct product quality (PQ). 25918883 1 60 theme Chinese 150:156 arg1 ovary 166:170 individual Chinese hamster ovary 139:170 individual Chinese hamster ovary (CHO) host cell lines 139:192 Much effort has been expended to improve the capabilities of individual Chinese hamster ovary (CHO) host cell lines to synthesize recombinant therapeutic proteins (rPs). 25918883 1 60 theme Chinese 150:156 arg1 CHO 173:175 CHO 173:175 CHO 173:175 Much effort has been expended to improve the capabilities of individual Chinese hamster ovary (CHO) host cell lines to synthesize recombinant therapeutic proteins (rPs). 25918883 4 61 theme IgG4 740:743 arg1 antibody 756:763 an IgG4 monoclonal antibody 737:763 an IgG4 monoclonal antibody (Mab) 737:769 In this work, we examine a panel of clonally derived host cell lines isolated from CHOK1SV for the ability to manufacture two model proteins, an IgG4 monoclonal antibody (Mab) and an Fc-fusion protein (etanercept). 25918883 4 61 theme IgG4 740:743 arg1 Mab 766:768 Mab 766:768 Mab 766:768 In this work, we examine a panel of clonally derived host cell lines isolated from CHOK1SV for the ability to manufacture two model proteins, an IgG4 monoclonal antibody (Mab) and an Fc-fusion protein (etanercept). 25918883 1 62 theme ovary 166:170 arg1 lines 188:192 individual Chinese hamster ovary (CHO) host cell lines 139:192 individual Chinese hamster ovary (CHO) host cell lines 139:192 Much effort has been expended to improve the capabilities of individual Chinese hamster ovary (CHO) host cell lines to synthesize recombinant therapeutic proteins (rPs). 25918883 9 63 theme host 1812:1815 arg1 lines 1822:1826 new host cell lines 1808:1826 new host cell lines with different performance characteristics 1808:1869 This work demonstrates the utility of leveraging diversity within the CHOK1SV pool to identify new host cell lines with different performance characteristics. 25918883 3 64 theme certain 494:500 arg1 types 512:516 certain molecular types 494:516 certain molecular types 494:516 Such a toolbox would contain a panel of hosts with specific capabilities to synthesize certain molecular types at high volumetric concentrations and with the correct product quality (PQ). 25918883 7 65 theme endoplasmic 1503:1513 arg1 reticulum 1515:1523 endoplasmic reticulum 1503:1523 endoplasmic reticulum (ER) 1503:1528 To further investigate the capabilities of these hosts to act as cell factories, we examined the glycosylation pathway gene expression profiles as well as the levels of endoplasmic reticulum (ER) and mitochondria in the untransfected hosts. 25918883 7 65 theme endoplasmic 1503:1513 arg1 ER 1526:1527 ER 1526:1527 ER 1526:1527 To further investigate the capabilities of these hosts to act as cell factories, we examined the glycosylation pathway gene expression profiles as well as the levels of endoplasmic reticulum (ER) and mitochondria in the untransfected hosts. 25918883 6 66 theme pool-produced 1010:1022 arg1 Mab 1024:1026 the stable pool-produced Mab 999:1026 the stable pool-produced Mab 999:1026 Furthermore, we examined the PQ attributes of the stable pool-produced Mab and etanercept (by N-glycan ultra performance liquid chromatography (UPLC) and liquid chromatography - tandem mass spectrometry (LC-MS/MS), respectively), and uncovered substantial variation between the host cell lines in Mab N-glycan micro-heterogeneity and etanercept N and O-linked macro-heterogeneity. 25918883 8 67 theme ER 1619:1620 arg1 mass 1622:1625 ER mass 1619:1625 ER mass 1619:1625 We uncovered a moderate correlation between ER mass and the volumetric product concentration in transient and stable pool Mab production. 25918883 1 68 theme host 178:181 arg1 lines 188:192 individual Chinese hamster ovary (CHO) host cell lines 139:192 individual Chinese hamster ovary (CHO) host cell lines 139:192 Much effort has been expended to improve the capabilities of individual Chinese hamster ovary (CHO) host cell lines to synthesize recombinant therapeutic proteins (rPs). 25918883 6 69 link O-linked 1304:1311 arg1 macro-heterogeneity 1313:1331 O-linked macro-heterogeneity 1304:1331 O-linked macro-heterogeneity 1304:1331 Furthermore, we examined the PQ attributes of the stable pool-produced Mab and etanercept (by N-glycan ultra performance liquid chromatography (UPLC) and liquid chromatography - tandem mass spectrometry (LC-MS/MS), respectively), and uncovered substantial variation between the host cell lines in Mab N-glycan micro-heterogeneity and etanercept N and O-linked macro-heterogeneity. 25918883 8 70 from concentration 1654:1666 arg1 production 1701:1710 transient and stable pool Mab production 1671:1710 transient and stable pool Mab production 1671:1710 We uncovered a moderate correlation between ER mass and the volumetric product concentration in transient and stable pool Mab production. 25918883 3 71 theme high 521:524 arg1 concentrations 537:550 high volumetric concentrations 521:550 high volumetric concentrations 521:550 Such a toolbox would contain a panel of hosts with specific capabilities to synthesize certain molecular types at high volumetric concentrations and with the correct product quality (PQ). 25918883 4 72 theme Fc-fusion 778:786 arg1 etanercept 797:806 etanercept 797:806 etanercept 797:806 In this work, we examine a panel of clonally derived host cell lines isolated from CHOK1SV for the ability to manufacture two model proteins, an IgG4 monoclonal antibody (Mab) and an Fc-fusion protein (etanercept). 25918883 4 72 theme Fc-fusion 778:786 arg1 protein 788:794 an Fc-fusion protein 775:794 an Fc-fusion protein (etanercept) 775:807 In this work, we examine a panel of clonally derived host cell lines isolated from CHOK1SV for the ability to manufacture two model proteins, an IgG4 monoclonal antibody (Mab) and an Fc-fusion protein (etanercept). 25918883 4 73 attach isolated 664:671 arg1 CHOK1SV 678:684 CHOK1SV 678:684 CHOK1SV 678:684 In this work, we examine a panel of clonally derived host cell lines isolated from CHOK1SV for the ability to manufacture two model proteins, an IgG4 monoclonal antibody (Mab) and an Fc-fusion protein (etanercept). 25918883 4 73 attach isolated 664:671 arg2 lines 658:662 clonally derived host cell lines 631:662 clonally derived host cell lines isolated from CHOK1SV for the ability to manufacture two model proteins, an IgG4 monoclonal antibody (Mab) and an Fc-fusion protein (etanercept) 631:807 In this work, we examine a panel of clonally derived host cell lines isolated from CHOK1SV for the ability to manufacture two model proteins, an IgG4 monoclonal antibody (Mab) and an Fc-fusion protein (etanercept). 25918883 5 74 theme stable 922:927 arg1 format 945:950 transient and stable pool production format 908:950 transient and stable pool production format 908:950 We show that these host cell lines vary in their relative ability to synthesize these proteins in transient and stable pool production format. 25918883 3 75 theme correct 565:571 arg1 PQ 590:591 PQ 590:591 PQ 590:591 Such a toolbox would contain a panel of hosts with specific capabilities to synthesize certain molecular types at high volumetric concentrations and with the correct product quality (PQ). 25918883 3 75 theme correct 565:571 arg1 quality 581:587 the correct product quality 561:587 the correct product quality (PQ) 561:592 Such a toolbox would contain a panel of hosts with specific capabilities to synthesize certain molecular types at high volumetric concentrations and with the correct product quality (PQ). 25918883 8 76 theme volumetric 1635:1644 arg1 concentration 1654:1666 the volumetric product concentration 1631:1666 the volumetric product concentration in transient and stable pool Mab production 1631:1710 We uncovered a moderate correlation between ER mass and the volumetric product concentration in transient and stable pool Mab production. 25918883 6 77 theme N-glycan 1254:1261 arg1 micro-heterogeneity 1263:1281 Mab N-glycan micro-heterogeneity 1250:1281 Mab N-glycan micro-heterogeneity 1250:1281 Furthermore, we examined the PQ attributes of the stable pool-produced Mab and etanercept (by N-glycan ultra performance liquid chromatography (UPLC) and liquid chromatography - tandem mass spectrometry (LC-MS/MS), respectively), and uncovered substantial variation between the host cell lines in Mab N-glycan micro-heterogeneity and etanercept N and O-linked macro-heterogeneity. 25918883 5 78 theme production 934:943 arg1 format 945:950 transient and stable pool production format 908:950 transient and stable pool production format 908:950 We show that these host cell lines vary in their relative ability to synthesize these proteins in transient and stable pool production format. 25918883 7 79 theme expression 1458:1467 arg1 profiles 1469:1476 the glycosylation pathway gene expression profiles 1427:1476 the glycosylation pathway gene expression profiles as well as the levels of endoplasmic reticulum (ER) and mitochondria in the untransfected hosts 1427:1572 To further investigate the capabilities of these hosts to act as cell factories, we examined the glycosylation pathway gene expression profiles as well as the levels of endoplasmic reticulum (ER) and mitochondria in the untransfected hosts. 25918883 6 80 theme performance 1062:1072 arg1 chromatography 1081:1094 N-glycan ultra performance liquid chromatography 1047:1094 N-glycan ultra performance liquid chromatography (UPLC) 1047:1101 Furthermore, we examined the PQ attributes of the stable pool-produced Mab and etanercept (by N-glycan ultra performance liquid chromatography (UPLC) and liquid chromatography - tandem mass spectrometry (LC-MS/MS), respectively), and uncovered substantial variation between the host cell lines in Mab N-glycan micro-heterogeneity and etanercept N and O-linked macro-heterogeneity. 25918883 6 80 theme performance 1062:1072 arg1 UPLC 1097:1100 UPLC 1097:1100 UPLC 1097:1100 Furthermore, we examined the PQ attributes of the stable pool-produced Mab and etanercept (by N-glycan ultra performance liquid chromatography (UPLC) and liquid chromatography - tandem mass spectrometry (LC-MS/MS), respectively), and uncovered substantial variation between the host cell lines in Mab N-glycan micro-heterogeneity and etanercept N and O-linked macro-heterogeneity. 25918883 6 81 from lines 1241:1245 arg1 etanercept 1287:1296 etanercept 1287:1296 etanercept 1287:1296 Furthermore, we examined the PQ attributes of the stable pool-produced Mab and etanercept (by N-glycan ultra performance liquid chromatography (UPLC) and liquid chromatography - tandem mass spectrometry (LC-MS/MS), respectively), and uncovered substantial variation between the host cell lines in Mab N-glycan micro-heterogeneity and etanercept N and O-linked macro-heterogeneity. 25918883 6 81 from lines 1241:1245 arg1 micro-heterogeneity 1263:1281 Mab N-glycan micro-heterogeneity 1250:1281 Mab N-glycan micro-heterogeneity 1250:1281 Furthermore, we examined the PQ attributes of the stable pool-produced Mab and etanercept (by N-glycan ultra performance liquid chromatography (UPLC) and liquid chromatography - tandem mass spectrometry (LC-MS/MS), respectively), and uncovered substantial variation between the host cell lines in Mab N-glycan micro-heterogeneity and etanercept N and O-linked macro-heterogeneity. 25918883 6 81 from lines 1241:1245 arg1 macro-heterogeneity 1313:1331 O-linked macro-heterogeneity 1304:1331 O-linked macro-heterogeneity 1304:1331 Furthermore, we examined the PQ attributes of the stable pool-produced Mab and etanercept (by N-glycan ultra performance liquid chromatography (UPLC) and liquid chromatography - tandem mass spectrometry (LC-MS/MS), respectively), and uncovered substantial variation between the host cell lines in Mab N-glycan micro-heterogeneity and etanercept N and O-linked macro-heterogeneity. 25918883 8 82 theme transient 1671:1679 arg1 production 1701:1710 transient and stable pool Mab production 1671:1710 transient and stable pool Mab production 1671:1710 We uncovered a moderate correlation between ER mass and the volumetric product concentration in transient and stable pool Mab production. 25918883 7 83 theme pathway 1445:1451 arg1 profiles 1469:1476 the glycosylation pathway gene expression profiles 1427:1476 the glycosylation pathway gene expression profiles as well as the levels of endoplasmic reticulum (ER) and mitochondria in the untransfected hosts 1427:1572 To further investigate the capabilities of these hosts to act as cell factories, we examined the glycosylation pathway gene expression profiles as well as the levels of endoplasmic reticulum (ER) and mitochondria in the untransfected hosts. 25918883 6 84 theme cell 1236:1239 arg1 lines 1241:1245 the host cell lines 1227:1245 the host cell lines in Mab N-glycan micro-heterogeneity and etanercept N and O-linked macro-heterogeneity 1227:1331 Furthermore, we examined the PQ attributes of the stable pool-produced Mab and etanercept (by N-glycan ultra performance liquid chromatography (UPLC) and liquid chromatography - tandem mass spectrometry (LC-MS/MS), respectively), and uncovered substantial variation between the host cell lines in Mab N-glycan micro-heterogeneity and etanercept N and O-linked macro-heterogeneity. 25918883 7 85 from levels 1493:1498 arg1 hosts 1568:1572 the untransfected hosts 1550:1572 the untransfected hosts 1550:1572 To further investigate the capabilities of these hosts to act as cell factories, we examined the glycosylation pathway gene expression profiles as well as the levels of endoplasmic reticulum (ER) and mitochondria in the untransfected hosts. 25918883 8 86 theme stable 1685:1690 arg1 production 1701:1710 transient and stable pool Mab production 1671:1710 transient and stable pool Mab production 1671:1710 We uncovered a moderate correlation between ER mass and the volumetric product concentration in transient and stable pool Mab production. 25918883 8 87 theme Mab 1697:1699 arg1 production 1701:1710 transient and stable pool Mab production 1671:1710 transient and stable pool Mab production 1671:1710 We uncovered a moderate correlation between ER mass and the volumetric product concentration in transient and stable pool Mab production. 25918883 7 88 theme untransfected 1554:1566 arg1 hosts 1568:1572 the untransfected hosts 1550:1572 the untransfected hosts 1550:1572 To further investigate the capabilities of these hosts to act as cell factories, we examined the glycosylation pathway gene expression profiles as well as the levels of endoplasmic reticulum (ER) and mitochondria in the untransfected hosts. 25918883 2 89 theme lines 380:384 arg1 toolbox 355:361 a toolbox 353:361 a toolbox of CHO host cell lines in biomanufacturing 353:404 However, given the increasing variety in rP molecular types and formats it may be advantageous to employ a toolbox of CHO host cell lines in biomanufacturing. 25918883 4 90 theme host 648:651 arg1 lines 658:662 clonally derived host cell lines 631:662 clonally derived host cell lines isolated from CHOK1SV for the ability to manufacture two model proteins, an IgG4 monoclonal antibody (Mab) and an Fc-fusion protein (etanercept) 631:807 In this work, we examine a panel of clonally derived host cell lines isolated from CHOK1SV for the ability to manufacture two model proteins, an IgG4 monoclonal antibody (Mab) and an Fc-fusion protein (etanercept). 25918883 6 91 theme O-linked 1304:1311 arg1 macro-heterogeneity 1313:1331 O-linked macro-heterogeneity 1304:1331 O-linked macro-heterogeneity 1304:1331 Furthermore, we examined the PQ attributes of the stable pool-produced Mab and etanercept (by N-glycan ultra performance liquid chromatography (UPLC) and liquid chromatography - tandem mass spectrometry (LC-MS/MS), respectively), and uncovered substantial variation between the host cell lines in Mab N-glycan micro-heterogeneity and etanercept N and O-linked macro-heterogeneity. 25918883 5 92 theme host 829:832 arg1 lines 839:843 these host cell lines 823:843 these host cell lines 823:843 We show that these host cell lines vary in their relative ability to synthesize these proteins in transient and stable pool production format. 25918883 2 93 theme host 370:373 arg1 lines 380:384 CHO host cell lines 366:384 CHO host cell lines 366:384 However, given the increasing variety in rP molecular types and formats it may be advantageous to employ a toolbox of CHO host cell lines in biomanufacturing. 25918883 9 94 with lines 1822:1826 arg1 characteristics 1855:1869 different performance characteristics 1833:1869 different performance characteristics 1833:1869 This work demonstrates the utility of leveraging diversity within the CHOK1SV pool to identify new host cell lines with different performance characteristics. 25918883 4 95 theme lines 658:662 arg1 panel 622:626 a panel 620:626 a panel of clonally derived host cell lines isolated from CHOK1SV for the ability to manufacture two model proteins, an IgG4 monoclonal antibody (Mab) and an Fc-fusion protein (etanercept) 620:807 In this work, we examine a panel of clonally derived host cell lines isolated from CHOK1SV for the ability to manufacture two model proteins, an IgG4 monoclonal antibody (Mab) and an Fc-fusion protein (etanercept). 25918883 4 96 theme model 721:725 arg1 proteins 727:734 two model proteins 717:734 two model proteins 717:734 In this work, we examine a panel of clonally derived host cell lines isolated from CHOK1SV for the ability to manufacture two model proteins, an IgG4 monoclonal antibody (Mab) and an Fc-fusion protein (etanercept). 25918883 0 97 theme Chinese 45:51 arg1 line 72:75 a Chinese hamster ovary cell line 43:75 a Chinese hamster ovary cell line 43:75 Diversity in host clone performance within a Chinese hamster ovary cell line. 25918883 6 98 theme stable 1003:1008 arg1 Mab 1024:1026 the stable pool-produced Mab 999:1026 the stable pool-produced Mab 999:1026 Furthermore, we examined the PQ attributes of the stable pool-produced Mab and etanercept (by N-glycan ultra performance liquid chromatography (UPLC) and liquid chromatography - tandem mass spectrometry (LC-MS/MS), respectively), and uncovered substantial variation between the host cell lines in Mab N-glycan micro-heterogeneity and etanercept N and O-linked macro-heterogeneity. 25918883 2 99 theme molecular 292:300 arg1 types 302:306 rP molecular types 289:306 rP molecular types 289:306 However, given the increasing variety in rP molecular types and formats it may be advantageous to employ a toolbox of CHO host cell lines in biomanufacturing. 25918883 7 100 theme cell 1399:1402 arg1 factories 1404:1412 cell factories 1399:1412 cell factories 1399:1412 To further investigate the capabilities of these hosts to act as cell factories, we examined the glycosylation pathway gene expression profiles as well as the levels of endoplasmic reticulum (ER) and mitochondria in the untransfected hosts. 25918883 5 101 theme relative 859:866 arg1 ability 868:874 their relative ability to synthesize these proteins in transient and stable pool production format 853:950 their relative ability to synthesize these proteins in transient and stable pool production format 853:950 We show that these host cell lines vary in their relative ability to synthesize these proteins in transient and stable pool production format. 25918883 9 102 theme different 1833:1841 arg1 characteristics 1855:1869 different performance characteristics 1833:1869 different performance characteristics 1833:1869 This work demonstrates the utility of leveraging diversity within the CHOK1SV pool to identify new host cell lines with different performance characteristics. 25918883 6 103 theme PQ 982:983 arg1 attributes 985:994 the PQ attributes 978:994 the PQ attributes of the stable pool-produced Mab and etanercept (by N-glycan ultra performance liquid chromatography (UPLC) and liquid chromatography - tandem mass spectrometry (LC-MS/MS), respectively) 978:1180 Furthermore, we examined the PQ attributes of the stable pool-produced Mab and etanercept (by N-glycan ultra performance liquid chromatography (UPLC) and liquid chromatography - tandem mass spectrometry (LC-MS/MS), respectively), and uncovered substantial variation between the host cell lines in Mab N-glycan micro-heterogeneity and etanercept N and O-linked macro-heterogeneity. 25918883 9 104 theme leveraging 1751:1760 arg1 diversity 1762:1770 leveraging diversity 1751:1770 leveraging diversity 1751:1770 This work demonstrates the utility of leveraging diversity within the CHOK1SV pool to identify new host cell lines with different performance characteristics. 25918883 1 105 theme recombinant 208:218 arg1 proteins 232:239 recombinant therapeutic proteins 208:239 recombinant therapeutic proteins (rPs) 208:245 Much effort has been expended to improve the capabilities of individual Chinese hamster ovary (CHO) host cell lines to synthesize recombinant therapeutic proteins (rPs). 25918883 1 105 theme recombinant 208:218 arg1 rPs 242:244 rPs 242:244 rPs 242:244 Much effort has been expended to improve the capabilities of individual Chinese hamster ovary (CHO) host cell lines to synthesize recombinant therapeutic proteins (rPs). 29058723 4 0 dep application 568:578 arg1 discover 680:687 discover 680:687 to discover OGT residues crucial for protein recognition 677:732 Data from mass spectrometry, X-ray crystallization, and biochemical and radiolabeled kinetic assays support the application of GEPs to rapidly report the impacts of OGT mutations on protein substrate or sugar binding and to discover OGT residues crucial for protein recognition. 29058723 4 0 dep application 568:578 arg1 report 599:604 report 599:604 to rapidly report the impacts of OGT mutations on protein substrate or sugar binding 588:671 Data from mass spectrometry, X-ray crystallization, and biochemical and radiolabeled kinetic assays support the application of GEPs to rapidly report the impacts of OGT mutations on protein substrate or sugar binding and to discover OGT residues crucial for protein recognition. 29058723 4 1 from assays 549:554 arg1 Data 456:459 Data 456:459 Data from mass spectrometry, X-ray crystallization, and biochemical and radiolabeled kinetic assays 456:554 Data from mass spectrometry, X-ray crystallization, and biochemical and radiolabeled kinetic assays support the application of GEPs to rapidly report the impacts of OGT mutations on protein substrate or sugar binding and to discover OGT residues crucial for protein recognition. 29058723 1 2 theme human 160:164 arg1 transferase 126:136 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase 84:136 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) 84:142 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is an essential human glycosyltransferase that adds O-GlcNAc modifications to numerous proteins. 29058723 1 2 theme human 160:164 arg1 glycosyltransferase 166:184 an essential human glycosyltransferase 147:184 an essential human glycosyltransferase that adds O-GlcNAc modifications to numerous proteins 147:238 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is an essential human glycosyltransferase that adds O-GlcNAc modifications to numerous proteins. 29058723 5 3 theme same 768:771 arg1 residues 773:780 the same residues 764:780 the same residues on the inner surface of the N-terminal domain 764:826 Interestingly, we found that the same residues on the inner surface of the N-terminal domain contribute to OGT interactions with different protein substrates. 29058723 5 4 theme inner 789:793 arg1 surface 795:801 the inner surface 785:801 the inner surface of the N-terminal domain 785:826 Interestingly, we found that the same residues on the inner surface of the N-terminal domain contribute to OGT interactions with different protein substrates. 29058723 7 5 theme OGT-substrate 1142:1154 arg1 binding 1156:1162 OGT-substrate binding 1142:1162 OGT-substrate binding 1142:1162 Hence, GEPs provide new strategies to dissect OGT-substrate binding and recognition. 29058723 4 6 theme protein 714:720 arg1 recognition 722:732 protein recognition 714:732 protein recognition 714:732 Data from mass spectrometry, X-ray crystallization, and biochemical and radiolabeled kinetic assays support the application of GEPs to rapidly report the impacts of OGT mutations on protein substrate or sugar binding and to discover OGT residues crucial for protein recognition. 29058723 1 7 link O-linked 84:91 arg1 glycosyltransferase 166:184 an essential human glycosyltransferase 147:184 an essential human glycosyltransferase that adds O-GlcNAc modifications to numerous proteins 147:238 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is an essential human glycosyltransferase that adds O-GlcNAc modifications to numerous proteins. 29058723 1 7 link O-linked 84:91 arg1 OGT 139:141 OGT 139:141 OGT 139:141 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is an essential human glycosyltransferase that adds O-GlcNAc modifications to numerous proteins. 29058723 1 7 link O-linked 84:91 arg1 transferase 126:136 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase 84:136 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) 84:142 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is an essential human glycosyltransferase that adds O-GlcNAc modifications to numerous proteins. 29058723 4 8 theme kinetic 541:547 arg1 assays 549:554 biochemical and radiolabeled kinetic assays 512:554 biochemical and radiolabeled kinetic assays 512:554 Data from mass spectrometry, X-ray crystallization, and biochemical and radiolabeled kinetic assays support the application of GEPs to rapidly report the impacts of OGT mutations on protein substrate or sugar binding and to discover OGT residues crucial for protein recognition. 29058723 4 9 theme OGT 621:623 arg1 mutations 625:633 OGT mutations 621:633 OGT mutations 621:633 Data from mass spectrometry, X-ray crystallization, and biochemical and radiolabeled kinetic assays support the application of GEPs to rapidly report the impacts of OGT mutations on protein substrate or sugar binding and to discover OGT residues crucial for protein recognition. 29058723 6 10 with crosslinking 939:950 arg1 substrates 973:982 acceptor substrates 964:982 acceptor substrates 964:982 By tuning reaction conditions, a GEP enables crosslinking of OGT with acceptor substrates in situ, affording a unique method to discover genuine substrates that weakly or transiently interact with OGT. 29058723 3 11 theme GlcNAc 358:363 arg1 GEPs 387:390 GEPs 387:390 GEPs 387:390 Here we report on GlcNAc electrophilic probes (GEPs) to expedite the characterization of OGT-substrate recognition. 29058723 3 11 theme GlcNAc 358:363 arg1 probes 379:384 GlcNAc electrophilic probes 358:384 GlcNAc electrophilic probes (GEPs) 358:391 Here we report on GlcNAc electrophilic probes (GEPs) to expedite the characterization of OGT-substrate recognition. 29058723 1 12 theme O-linked 84:91 arg1 glycosyltransferase 166:184 an essential human glycosyltransferase 147:184 an essential human glycosyltransferase that adds O-GlcNAc modifications to numerous proteins 147:238 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is an essential human glycosyltransferase that adds O-GlcNAc modifications to numerous proteins. 29058723 1 12 theme O-linked 84:91 arg1 OGT 139:141 OGT 139:141 OGT 139:141 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is an essential human glycosyltransferase that adds O-GlcNAc modifications to numerous proteins. 29058723 1 12 theme O-linked 84:91 arg1 transferase 126:136 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase 84:136 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) 84:142 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is an essential human glycosyltransferase that adds O-GlcNAc modifications to numerous proteins. 29058723 1 13 theme O-GlcNAc 196:203 arg1 modifications 205:217 O-GlcNAc modifications 196:217 O-GlcNAc modifications 196:217 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is an essential human glycosyltransferase that adds O-GlcNAc modifications to numerous proteins. 29058723 3 14 theme electrophilic 365:377 arg1 GEPs 387:390 GEPs 387:390 GEPs 387:390 Here we report on GlcNAc electrophilic probes (GEPs) to expedite the characterization of OGT-substrate recognition. 29058723 3 14 theme electrophilic 365:377 arg1 probes 379:384 GlcNAc electrophilic probes 358:384 GlcNAc electrophilic probes (GEPs) 358:391 Here we report on GlcNAc electrophilic probes (GEPs) to expedite the characterization of OGT-substrate recognition. 29058723 4 15 theme biochemical 512:522 arg1 assays 549:554 biochemical and radiolabeled kinetic assays 512:554 biochemical and radiolabeled kinetic assays 512:554 Data from mass spectrometry, X-ray crystallization, and biochemical and radiolabeled kinetic assays support the application of GEPs to rapidly report the impacts of OGT mutations on protein substrate or sugar binding and to discover OGT residues crucial for protein recognition. 29058723 7 16 theme new 1116:1118 arg1 strategies 1120:1129 new strategies 1116:1129 new strategies to dissect OGT-substrate binding and recognition 1116:1178 Hence, GEPs provide new strategies to dissect OGT-substrate binding and recognition. 29058723 1 17 theme β-N-acetylglucosamine 93:113 arg1 glycosyltransferase 166:184 an essential human glycosyltransferase 147:184 an essential human glycosyltransferase that adds O-GlcNAc modifications to numerous proteins 147:238 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is an essential human glycosyltransferase that adds O-GlcNAc modifications to numerous proteins. 29058723 1 17 theme β-N-acetylglucosamine 93:113 arg1 OGT 139:141 OGT 139:141 OGT 139:141 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is an essential human glycosyltransferase that adds O-GlcNAc modifications to numerous proteins. 29058723 1 17 theme β-N-acetylglucosamine 93:113 arg1 transferase 126:136 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase 84:136 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) 84:142 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is an essential human glycosyltransferase that adds O-GlcNAc modifications to numerous proteins. 29058723 4 18 from impacts 610:616 arg1 binding 665:671 sugar binding 659:671 sugar binding 659:671 Data from mass spectrometry, X-ray crystallization, and biochemical and radiolabeled kinetic assays support the application of GEPs to rapidly report the impacts of OGT mutations on protein substrate or sugar binding and to discover OGT residues crucial for protein recognition. 29058723 4 18 from impacts 610:616 arg1 substrate 646:654 protein substrate 638:654 protein substrate 638:654 Data from mass spectrometry, X-ray crystallization, and biochemical and radiolabeled kinetic assays support the application of GEPs to rapidly report the impacts of OGT mutations on protein substrate or sugar binding and to discover OGT residues crucial for protein recognition. 29058723 5 19 theme domain 821:826 arg1 surface 795:801 the inner surface 785:801 the inner surface of the N-terminal domain 785:826 Interestingly, we found that the same residues on the inner surface of the N-terminal domain contribute to OGT interactions with different protein substrates. 29058723 6 20 theme reaction 904:911 arg1 conditions 913:922 tuning reaction conditions 897:922 tuning reaction conditions 897:922 By tuning reaction conditions, a GEP enables crosslinking of OGT with acceptor substrates in situ, affording a unique method to discover genuine substrates that weakly or transiently interact with OGT. 29058723 5 21 with interactions 846:857 arg1 substrates 882:891 different protein substrates 864:891 different protein substrates 864:891 Interestingly, we found that the same residues on the inner surface of the N-terminal domain contribute to OGT interactions with different protein substrates. 29058723 3 22 theme recognition 443:453 arg1 characterization 409:424 the characterization 405:424 the characterization of OGT-substrate recognition 405:453 Here we report on GlcNAc electrophilic probes (GEPs) to expedite the characterization of OGT-substrate recognition. 29058723 0 23 theme Electrophilic 0:12 arg1 probes 14:19 Electrophilic probes 0:19 Electrophilic probes for deciphering substrate recognition by O-GlcNAc transferase 0:81 Electrophilic probes for deciphering substrate recognition by O-GlcNAc transferase. 29058723 4 24 from crystallization 491:505 arg1 Data 456:459 Data 456:459 Data from mass spectrometry, X-ray crystallization, and biochemical and radiolabeled kinetic assays 456:554 Data from mass spectrometry, X-ray crystallization, and biochemical and radiolabeled kinetic assays support the application of GEPs to rapidly report the impacts of OGT mutations on protein substrate or sugar binding and to discover OGT residues crucial for protein recognition. 29058723 1 25 theme O-GlcNAc 116:123 arg1 glycosyltransferase 166:184 an essential human glycosyltransferase 147:184 an essential human glycosyltransferase that adds O-GlcNAc modifications to numerous proteins 147:238 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is an essential human glycosyltransferase that adds O-GlcNAc modifications to numerous proteins. 29058723 1 25 theme O-GlcNAc 116:123 arg1 OGT 139:141 OGT 139:141 OGT 139:141 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is an essential human glycosyltransferase that adds O-GlcNAc modifications to numerous proteins. 29058723 1 25 theme O-GlcNAc 116:123 arg1 transferase 126:136 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase 84:136 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) 84:142 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is an essential human glycosyltransferase that adds O-GlcNAc modifications to numerous proteins. 29058723 4 26 theme OGT 689:691 arg1 residues 693:700 OGT residues 689:700 OGT residues crucial for protein recognition 689:732 Data from mass spectrometry, X-ray crystallization, and biochemical and radiolabeled kinetic assays support the application of GEPs to rapidly report the impacts of OGT mutations on protein substrate or sugar binding and to discover OGT residues crucial for protein recognition. 29058723 4 27 theme GEPs 583:586 arg1 application 568:578 the application 564:578 the application of GEPs to rapidly report the impacts of OGT mutations on protein substrate or sugar binding and to discover OGT residues crucial for protein recognition 564:732 Data from mass spectrometry, X-ray crystallization, and biochemical and radiolabeled kinetic assays support the application of GEPs to rapidly report the impacts of OGT mutations on protein substrate or sugar binding and to discover OGT residues crucial for protein recognition. 29058723 2 28 theme protein 320:326 arg1 substrates 328:337 various protein substrates 312:337 various protein substrates 312:337 However, little is known about the mechanism with which OGT recognizes various protein substrates. 29058723 4 29 theme sugar 659:663 arg1 binding 665:671 sugar binding 659:671 sugar binding 659:671 Data from mass spectrometry, X-ray crystallization, and biochemical and radiolabeled kinetic assays support the application of GEPs to rapidly report the impacts of OGT mutations on protein substrate or sugar binding and to discover OGT residues crucial for protein recognition. 29058723 5 30 theme OGT 842:844 arg1 interactions 846:857 OGT interactions 842:857 OGT interactions with different protein substrates 842:891 Interestingly, we found that the same residues on the inner surface of the N-terminal domain contribute to OGT interactions with different protein substrates. 29058723 6 31 theme tuning 897:902 arg1 conditions 913:922 tuning reaction conditions 897:922 tuning reaction conditions 897:922 By tuning reaction conditions, a GEP enables crosslinking of OGT with acceptor substrates in situ, affording a unique method to discover genuine substrates that weakly or transiently interact with OGT. 29058723 2 32 theme various 312:318 arg1 substrates 328:337 various protein substrates 312:337 various protein substrates 312:337 However, little is known about the mechanism with which OGT recognizes various protein substrates. 29058723 1 33 theme numerous 222:229 arg1 proteins 231:238 numerous proteins 222:238 numerous proteins 222:238 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is an essential human glycosyltransferase that adds O-GlcNAc modifications to numerous proteins. 29058723 4 34 from spectrometry 471:482 arg1 Data 456:459 Data 456:459 Data from mass spectrometry, X-ray crystallization, and biochemical and radiolabeled kinetic assays 456:554 Data from mass spectrometry, X-ray crystallization, and biochemical and radiolabeled kinetic assays support the application of GEPs to rapidly report the impacts of OGT mutations on protein substrate or sugar binding and to discover OGT residues crucial for protein recognition. 29058723 4 35 theme mass 466:469 arg1 spectrometry 471:482 mass spectrometry 466:482 mass spectrometry 466:482 Data from mass spectrometry, X-ray crystallization, and biochemical and radiolabeled kinetic assays support the application of GEPs to rapidly report the impacts of OGT mutations on protein substrate or sugar binding and to discover OGT residues crucial for protein recognition. 29058723 5 36 theme different 864:872 arg1 substrates 882:891 different protein substrates 864:891 different protein substrates 864:891 Interestingly, we found that the same residues on the inner surface of the N-terminal domain contribute to OGT interactions with different protein substrates. 29058723 0 37 theme substrate 37:45 arg1 recognition 47:57 substrate recognition 37:57 substrate recognition by O-GlcNAc transferase 37:81 Electrophilic probes for deciphering substrate recognition by O-GlcNAc transferase. 29058723 3 38 theme OGT-substrate 429:441 arg1 recognition 443:453 OGT-substrate recognition 429:453 OGT-substrate recognition 429:453 Here we report on GlcNAc electrophilic probes (GEPs) to expedite the characterization of OGT-substrate recognition. 29058723 4 39 theme X-ray 485:489 arg1 crystallization 491:505 X-ray crystallization 485:505 X-ray crystallization 485:505 Data from mass spectrometry, X-ray crystallization, and biochemical and radiolabeled kinetic assays support the application of GEPs to rapidly report the impacts of OGT mutations on protein substrate or sugar binding and to discover OGT residues crucial for protein recognition. 29058723 5 40 theme protein 874:880 arg1 substrates 882:891 different protein substrates 864:891 different protein substrates 864:891 Interestingly, we found that the same residues on the inner surface of the N-terminal domain contribute to OGT interactions with different protein substrates. 29058723 0 41 theme O-GlcNAc 62:69 arg1 transferase 71:81 O-GlcNAc transferase 62:81 O-GlcNAc transferase 62:81 Electrophilic probes for deciphering substrate recognition by O-GlcNAc transferase. 29058723 6 42 theme acceptor 964:971 arg1 substrates 973:982 acceptor substrates 964:982 acceptor substrates 964:982 By tuning reaction conditions, a GEP enables crosslinking of OGT with acceptor substrates in situ, affording a unique method to discover genuine substrates that weakly or transiently interact with OGT. 29058723 5 43 theme N-terminal 810:819 arg1 domain 821:826 the N-terminal domain 806:826 the N-terminal domain 806:826 Interestingly, we found that the same residues on the inner surface of the N-terminal domain contribute to OGT interactions with different protein substrates. 29058723 6 44 theme OGT 955:957 arg1 crosslinking 939:950 crosslinking 939:950 crosslinking of OGT with acceptor substrates 939:982 By tuning reaction conditions, a GEP enables crosslinking of OGT with acceptor substrates in situ, affording a unique method to discover genuine substrates that weakly or transiently interact with OGT. 29058723 5 45 from residues 773:780 arg1 surface 795:801 the inner surface 785:801 the inner surface of the N-terminal domain 785:826 Interestingly, we found that the same residues on the inner surface of the N-terminal domain contribute to OGT interactions with different protein substrates. 29058723 4 46 theme crucial 702:708 arg1 residues 693:700 OGT residues 689:700 OGT residues crucial for protein recognition 689:732 Data from mass spectrometry, X-ray crystallization, and biochemical and radiolabeled kinetic assays support the application of GEPs to rapidly report the impacts of OGT mutations on protein substrate or sugar binding and to discover OGT residues crucial for protein recognition. 29058723 4 47 theme mutations 625:633 arg1 impacts 610:616 the impacts 606:616 the impacts of OGT mutations on protein substrate or sugar binding 606:671 Data from mass spectrometry, X-ray crystallization, and biochemical and radiolabeled kinetic assays support the application of GEPs to rapidly report the impacts of OGT mutations on protein substrate or sugar binding and to discover OGT residues crucial for protein recognition. 29058723 6 48 theme genuine 1031:1037 arg1 substrates 1039:1048 genuine substrates 1031:1048 genuine substrates that weakly or transiently interact with OGT 1031:1093 By tuning reaction conditions, a GEP enables crosslinking of OGT with acceptor substrates in situ, affording a unique method to discover genuine substrates that weakly or transiently interact with OGT. 29058723 6 49 theme unique 1005:1010 arg1 method 1012:1017 a unique method 1003:1017 a unique method to discover genuine substrates that weakly or transiently interact with OGT 1003:1093 By tuning reaction conditions, a GEP enables crosslinking of OGT with acceptor substrates in situ, affording a unique method to discover genuine substrates that weakly or transiently interact with OGT. 29058723 4 50 theme radiolabeled 528:539 arg1 assays 549:554 biochemical and radiolabeled kinetic assays 512:554 biochemical and radiolabeled kinetic assays 512:554 Data from mass spectrometry, X-ray crystallization, and biochemical and radiolabeled kinetic assays support the application of GEPs to rapidly report the impacts of OGT mutations on protein substrate or sugar binding and to discover OGT residues crucial for protein recognition. 29058723 1 51 theme essential 150:158 arg1 transferase 126:136 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase 84:136 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) 84:142 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is an essential human glycosyltransferase that adds O-GlcNAc modifications to numerous proteins. 29058723 1 51 theme essential 150:158 arg1 glycosyltransferase 166:184 an essential human glycosyltransferase 147:184 an essential human glycosyltransferase that adds O-GlcNAc modifications to numerous proteins 147:238 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is an essential human glycosyltransferase that adds O-GlcNAc modifications to numerous proteins. 29058723 4 52 theme protein 638:644 arg1 substrate 646:654 protein substrate 638:654 protein substrate 638:654 Data from mass spectrometry, X-ray crystallization, and biochemical and radiolabeled kinetic assays support the application of GEPs to rapidly report the impacts of OGT mutations on protein substrate or sugar binding and to discover OGT residues crucial for protein recognition. 28259907 0 0 from migration 25:33 arg1 cells 72:76 human ovarian cancer cells 51:76 human ovarian cancer cells 51:76 O-GlcNAcylation promotes migration and invasion in human ovarian cancer cells via the RhoA/ROCK/MLC pathway. 28259907 7 1 with inhibition 1288:1297 arg1 Y‑27632 1321:1327 Y‑27632 1321:1327 Y‑27632 1321:1327 In addition, RhoA silencing via RNA interference and inhibition of ROCK activity with Y‑27632 prevented Thiamet‑G‑induced increases in cell migration and invasion. 28259907 6 2 theme ROCK 1122:1125 arg1 chain 1152:1156 myosin light chain 1139:1156 myosin light chain (MLC) 1139:1162 Furthermore, a pull‑down assay and western blot analysis demonstrated that Thiamet-G treatment enhanced RhoA activity and the phosphorylation of the Rho‑associated protein kinase (ROCK) substrate, myosin light chain (MLC), while OGT silencing attenuated RhoA activity and MLC phosphorylation. 28259907 6 2 theme ROCK 1122:1125 arg1 substrate 1128:1136 the Rho‑associated protein kinase (ROCK) substrate 1087:1136 the Rho‑associated protein kinase (ROCK) substrate 1087:1136 Furthermore, a pull‑down assay and western blot analysis demonstrated that Thiamet-G treatment enhanced RhoA activity and the phosphorylation of the Rho‑associated protein kinase (ROCK) substrate, myosin light chain (MLC), while OGT silencing attenuated RhoA activity and MLC phosphorylation. 28259907 3 3 theme cancer 529:534 arg1 types 514:518 several types 506:518 several types of human cancer 506:534 Accumulating evidence suggests that O-GlcNAcylation is associated with the malignancy of several types of human cancer. 28259907 4 4 theme global 612:617 arg1 levels 628:633 global O‑GlcNAc levels 612:633 global O‑GlcNAc levels 612:633 To investigate the effect of O-GlcNAcylation on ovarian cancer phenotypes, global O‑GlcNAc levels were decreased by OGT silencing through RNA interference and increased by inhibiting OGA activity with Thiamet‑G. 28259907 6 5 theme Rho‑associated 1091:1104 arg1 chain 1152:1156 myosin light chain 1139:1156 myosin light chain (MLC) 1139:1162 Furthermore, a pull‑down assay and western blot analysis demonstrated that Thiamet-G treatment enhanced RhoA activity and the phosphorylation of the Rho‑associated protein kinase (ROCK) substrate, myosin light chain (MLC), while OGT silencing attenuated RhoA activity and MLC phosphorylation. 28259907 6 5 theme Rho‑associated 1091:1104 arg1 substrate 1128:1136 the Rho‑associated protein kinase (ROCK) substrate 1087:1136 the Rho‑associated protein kinase (ROCK) substrate 1087:1136 Furthermore, a pull‑down assay and western blot analysis demonstrated that Thiamet-G treatment enhanced RhoA activity and the phosphorylation of the Rho‑associated protein kinase (ROCK) substrate, myosin light chain (MLC), while OGT silencing attenuated RhoA activity and MLC phosphorylation. 28259907 7 6 theme activity 1307:1314 arg1 inhibition 1288:1297 inhibition 1288:1297 inhibition of ROCK activity with Y‑27632 1288:1327 In addition, RhoA silencing via RNA interference and inhibition of ROCK activity with Y‑27632 prevented Thiamet‑G‑induced increases in cell migration and invasion. 28259907 7 6 theme activity 1307:1314 arg1 interference 1271:1282 RNA interference 1267:1282 RNA interference 1267:1282 In addition, RhoA silencing via RNA interference and inhibition of ROCK activity with Y‑27632 prevented Thiamet‑G‑induced increases in cell migration and invasion. 28259907 5 7 theme SKOV3 845:849 arg1 cells 867:871 SKOV3 and 59M ovarian cells 845:871 cells 867:871 Transwell assay results demonstrated that OGT silencing inhibited the migration and invasion of SKOV3 and 59M ovarian cells in vitro, while Thiamet‑G treatment promoted migration and invasion. 28259907 2 8 attach removal 265:271 arg2 O‑GlcNAc 308:315 O‑GlcNAc 308:315 O‑GlcNAc 308:315 The addition and removal of O‑Linked β-N-acetylglucosamine (O‑GlcNAc) on target proteins is catalyzed by O‑GlcNAc transferase (OGT) and O‑GlcNAcase (OGA), respectively. 28259907 2 8 attach removal 265:271 arg2 β-N-acetylglucosamine 285:305 O‑Linked β-N-acetylglucosamine 276:305 O‑Linked β-N-acetylglucosamine (O‑GlcNAc) 276:316 The addition and removal of O‑Linked β-N-acetylglucosamine (O‑GlcNAc) on target proteins is catalyzed by O‑GlcNAc transferase (OGT) and O‑GlcNAcase (OGA), respectively. 28259907 2 8 attach removal 265:271 arg3 proteins 328:335 target proteins 321:335 target proteins 321:335 The addition and removal of O‑Linked β-N-acetylglucosamine (O‑GlcNAc) on target proteins is catalyzed by O‑GlcNAc transferase (OGT) and O‑GlcNAcase (OGA), respectively. 28259907 7 9 theme RhoA 1248:1251 arg1 silencing 1253:1261 RhoA silencing 1248:1261 RhoA silencing via RNA interference and inhibition of ROCK activity with Y‑27632 1248:1327 In addition, RhoA silencing via RNA interference and inhibition of ROCK activity with Y‑27632 prevented Thiamet‑G‑induced increases in cell migration and invasion. 28259907 6 10 theme pull‑down 957:965 arg1 assay 967:971 a pull‑down assay 955:971 a pull‑down assay 955:971 Furthermore, a pull‑down assay and western blot analysis demonstrated that Thiamet-G treatment enhanced RhoA activity and the phosphorylation of the Rho‑associated protein kinase (ROCK) substrate, myosin light chain (MLC), while OGT silencing attenuated RhoA activity and MLC phosphorylation. 28259907 2 11 theme target 321:326 arg1 proteins 328:335 target proteins 321:335 target proteins 321:335 The addition and removal of O‑Linked β-N-acetylglucosamine (O‑GlcNAc) on target proteins is catalyzed by O‑GlcNAc transferase (OGT) and O‑GlcNAcase (OGA), respectively. 28259907 0 12 theme RhoA/ROCK/MLC 86:98 arg1 pathway 100:106 the RhoA/ROCK/MLC pathway 82:106 the RhoA/ROCK/MLC pathway 82:106 O-GlcNAcylation promotes migration and invasion in human ovarian cancer cells via the RhoA/ROCK/MLC pathway. 28259907 9 13 dep diagnosis 1587:1595 arg1 the 1583:1585 the 1583:1585 the 1583:1585 Therefore, O‑GlcNAcylation may be a potential target for the diagnosis and treatment of ovarian cancer. 28259907 2 14 from addition 252:259 arg1 proteins 328:335 target proteins 321:335 target proteins 321:335 The addition and removal of O‑Linked β-N-acetylglucosamine (O‑GlcNAc) on target proteins is catalyzed by O‑GlcNAc transferase (OGT) and O‑GlcNAcase (OGA), respectively. 28259907 2 15 theme O‑GlcNAc 353:360 arg1 OGT 375:377 OGT 375:377 OGT 375:377 The addition and removal of O‑Linked β-N-acetylglucosamine (O‑GlcNAc) on target proteins is catalyzed by O‑GlcNAc transferase (OGT) and O‑GlcNAcase (OGA), respectively. 28259907 2 15 theme O‑GlcNAc 353:360 arg1 transferase 362:372 O‑GlcNAc transferase 353:372 O‑GlcNAc transferase (OGT) 353:378 The addition and removal of O‑Linked β-N-acetylglucosamine (O‑GlcNAc) on target proteins is catalyzed by O‑GlcNAc transferase (OGT) and O‑GlcNAcase (OGA), respectively. 28259907 5 16 theme OGT 791:793 arg1 silencing 795:803 OGT silencing 791:803 OGT silencing 791:803 Transwell assay results demonstrated that OGT silencing inhibited the migration and invasion of SKOV3 and 59M ovarian cells in vitro, while Thiamet‑G treatment promoted migration and invasion. 28259907 7 17 theme ROCK 1302:1305 arg1 activity 1307:1314 ROCK activity 1302:1314 ROCK activity 1302:1314 In addition, RhoA silencing via RNA interference and inhibition of ROCK activity with Y‑27632 prevented Thiamet‑G‑induced increases in cell migration and invasion. 28259907 4 18 theme O‑GlcNAc 619:626 arg1 levels 628:633 global O‑GlcNAc levels 612:633 global O‑GlcNAc levels 612:633 To investigate the effect of O-GlcNAcylation on ovarian cancer phenotypes, global O‑GlcNAc levels were decreased by OGT silencing through RNA interference and increased by inhibiting OGA activity with Thiamet‑G. 28259907 6 19 theme OGT 1171:1173 arg1 silencing 1175:1183 OGT silencing 1171:1183 OGT silencing 1171:1183 Furthermore, a pull‑down assay and western blot analysis demonstrated that Thiamet-G treatment enhanced RhoA activity and the phosphorylation of the Rho‑associated protein kinase (ROCK) substrate, myosin light chain (MLC), while OGT silencing attenuated RhoA activity and MLC phosphorylation. 28259907 3 20 theme Accumulating 417:428 arg1 evidence 430:437 Accumulating evidence 417:437 Accumulating evidence 417:437 Accumulating evidence suggests that O-GlcNAcylation is associated with the malignancy of several types of human cancer. 28259907 6 21 theme MLC 1214:1216 arg1 phosphorylation 1218:1232 MLC phosphorylation 1214:1232 MLC phosphorylation 1214:1232 Furthermore, a pull‑down assay and western blot analysis demonstrated that Thiamet-G treatment enhanced RhoA activity and the phosphorylation of the Rho‑associated protein kinase (ROCK) substrate, myosin light chain (MLC), while OGT silencing attenuated RhoA activity and MLC phosphorylation. 28259907 2 22 from removal 265:271 arg1 proteins 328:335 target proteins 321:335 target proteins 321:335 The addition and removal of O‑Linked β-N-acetylglucosamine (O‑GlcNAc) on target proteins is catalyzed by O‑GlcNAc transferase (OGT) and O‑GlcNAcase (OGA), respectively. 28259907 6 23 theme myosin 1139:1144 arg1 MLC 1159:1161 MLC 1159:1161 MLC 1159:1161 Furthermore, a pull‑down assay and western blot analysis demonstrated that Thiamet-G treatment enhanced RhoA activity and the phosphorylation of the Rho‑associated protein kinase (ROCK) substrate, myosin light chain (MLC), while OGT silencing attenuated RhoA activity and MLC phosphorylation. 28259907 6 23 theme myosin 1139:1144 arg1 chain 1152:1156 myosin light chain 1139:1156 myosin light chain (MLC) 1139:1162 Furthermore, a pull‑down assay and western blot analysis demonstrated that Thiamet-G treatment enhanced RhoA activity and the phosphorylation of the Rho‑associated protein kinase (ROCK) substrate, myosin light chain (MLC), while OGT silencing attenuated RhoA activity and MLC phosphorylation. 28259907 6 23 theme myosin 1139:1144 arg1 substrate 1128:1136 the Rho‑associated protein kinase (ROCK) substrate 1087:1136 the Rho‑associated protein kinase (ROCK) substrate 1087:1136 Furthermore, a pull‑down assay and western blot analysis demonstrated that Thiamet-G treatment enhanced RhoA activity and the phosphorylation of the Rho‑associated protein kinase (ROCK) substrate, myosin light chain (MLC), while OGT silencing attenuated RhoA activity and MLC phosphorylation. 28259907 5 24 theme 59M 855:857 arg1 cells 867:871 SKOV3 and 59M ovarian cells 845:871 cells 867:871 Transwell assay results demonstrated that OGT silencing inhibited the migration and invasion of SKOV3 and 59M ovarian cells in vitro, while Thiamet‑G treatment promoted migration and invasion. 28259907 0 25 from invasion 39:46 arg1 cells 72:76 human ovarian cancer cells 51:76 human ovarian cancer cells 51:76 O-GlcNAcylation promotes migration and invasion in human ovarian cancer cells via the RhoA/ROCK/MLC pathway. 28259907 7 26 theme RNA 1267:1269 arg1 interference 1271:1282 RNA interference 1267:1282 RNA interference 1267:1282 In addition, RhoA silencing via RNA interference and inhibition of ROCK activity with Y‑27632 prevented Thiamet‑G‑induced increases in cell migration and invasion. 28259907 6 27 theme RhoA 1046:1049 arg1 activity 1051:1058 RhoA activity 1046:1058 RhoA activity 1046:1058 Furthermore, a pull‑down assay and western blot analysis demonstrated that Thiamet-G treatment enhanced RhoA activity and the phosphorylation of the Rho‑associated protein kinase (ROCK) substrate, myosin light chain (MLC), while OGT silencing attenuated RhoA activity and MLC phosphorylation. 28259907 5 28 theme ovarian 859:865 arg1 cells 867:871 SKOV3 and 59M ovarian cells 845:871 cells 867:871 Transwell assay results demonstrated that OGT silencing inhibited the migration and invasion of SKOV3 and 59M ovarian cells in vitro, while Thiamet‑G treatment promoted migration and invasion. 28259907 4 29 theme ovarian 585:591 arg1 phenotypes 600:609 ovarian cancer phenotypes 585:609 ovarian cancer phenotypes 585:609 To investigate the effect of O-GlcNAcylation on ovarian cancer phenotypes, global O‑GlcNAc levels were decreased by OGT silencing through RNA interference and increased by inhibiting OGA activity with Thiamet‑G. 28259907 6 30 theme substrate 1128:1136 arg1 activity 1051:1058 RhoA activity 1046:1058 RhoA activity 1046:1058 Furthermore, a pull‑down assay and western blot analysis demonstrated that Thiamet-G treatment enhanced RhoA activity and the phosphorylation of the Rho‑associated protein kinase (ROCK) substrate, myosin light chain (MLC), while OGT silencing attenuated RhoA activity and MLC phosphorylation. 28259907 6 30 theme substrate 1128:1136 arg1 phosphorylation 1068:1082 the phosphorylation 1064:1082 the phosphorylation of the Rho‑associated protein kinase (ROCK) substrate, myosin light chain (MLC) 1064:1162 Furthermore, a pull‑down assay and western blot analysis demonstrated that Thiamet-G treatment enhanced RhoA activity and the phosphorylation of the Rho‑associated protein kinase (ROCK) substrate, myosin light chain (MLC), while OGT silencing attenuated RhoA activity and MLC phosphorylation. 28259907 5 31 theme cells 867:871 arg1 invasion 833:840 invasion 833:840 invasion 833:840 Transwell assay results demonstrated that OGT silencing inhibited the migration and invasion of SKOV3 and 59M ovarian cells in vitro, while Thiamet‑G treatment promoted migration and invasion. 28259907 5 31 theme cells 867:871 arg1 migration 819:827 migration 819:827 migration 819:827 Transwell assay results demonstrated that OGT silencing inhibited the migration and invasion of SKOV3 and 59M ovarian cells in vitro, while Thiamet‑G treatment promoted migration and invasion. 28259907 7 32 with interference 1271:1282 arg1 Y‑27632 1321:1327 Y‑27632 1321:1327 Y‑27632 1321:1327 In addition, RhoA silencing via RNA interference and inhibition of ROCK activity with Y‑27632 prevented Thiamet‑G‑induced increases in cell migration and invasion. 28259907 5 33 dep migration 819:827 arg1 the 815:817 the 815:817 the 815:817 Transwell assay results demonstrated that OGT silencing inhibited the migration and invasion of SKOV3 and 59M ovarian cells in vitro, while Thiamet‑G treatment promoted migration and invasion. 28259907 8 34 theme cells 1479:1483 arg1 motility 1452:1459 the motility 1448:1459 the motility of ovarian cancer cells 1448:1483 These data suggest that O‑GlcNAcylation augments the motility of ovarian cancer cells via the RhoA/ROCK/MLC signaling pathway. 28259907 4 35 from effect 556:561 arg1 phenotypes 600:609 ovarian cancer phenotypes 585:609 ovarian cancer phenotypes 585:609 To investigate the effect of O-GlcNAcylation on ovarian cancer phenotypes, global O‑GlcNAc levels were decreased by OGT silencing through RNA interference and increased by inhibiting OGA activity with Thiamet‑G. 28259907 8 36 theme cancer 1472:1477 arg1 cells 1479:1483 ovarian cancer cells 1464:1483 ovarian cancer cells 1464:1483 These data suggest that O‑GlcNAcylation augments the motility of ovarian cancer cells via the RhoA/ROCK/MLC signaling pathway. 28259907 2 37 dep addition 252:259 arg1 The 248:250 The 248:250 The 248:250 The addition and removal of O‑Linked β-N-acetylglucosamine (O‑GlcNAc) on target proteins is catalyzed by O‑GlcNAc transferase (OGT) and O‑GlcNAcase (OGA), respectively. 28259907 5 38 theme Transwell 749:757 arg1 results 765:771 Transwell assay results 749:771 Transwell assay results 749:771 Transwell assay results demonstrated that OGT silencing inhibited the migration and invasion of SKOV3 and 59M ovarian cells in vitro, while Thiamet‑G treatment promoted migration and invasion. 28259907 9 39 theme ovarian 1614:1620 arg1 cancer 1622:1627 ovarian cancer 1614:1627 ovarian cancer 1614:1627 Therefore, O‑GlcNAcylation may be a potential target for the diagnosis and treatment of ovarian cancer. 28259907 1 40 theme cellular 228:235 arg1 functions 237:245 multiple cellular functions 219:245 multiple cellular functions 219:245 O-GlcNAcylation is a dynamic and reversible post-translational modification associated with the regulation of multiple cellular functions. 28259907 4 41 theme cancer 593:598 arg1 phenotypes 600:609 ovarian cancer phenotypes 585:609 ovarian cancer phenotypes 585:609 To investigate the effect of O-GlcNAcylation on ovarian cancer phenotypes, global O‑GlcNAc levels were decreased by OGT silencing through RNA interference and increased by inhibiting OGA activity with Thiamet‑G. 28259907 5 42 theme assay 759:763 arg1 results 765:771 Transwell assay results 749:771 Transwell assay results 749:771 Transwell assay results demonstrated that OGT silencing inhibited the migration and invasion of SKOV3 and 59M ovarian cells in vitro, while Thiamet‑G treatment promoted migration and invasion. 28259907 5 43 theme Thiamet‑G 889:897 arg1 treatment 899:907 Thiamet‑G treatment 889:907 Thiamet‑G treatment 889:907 Transwell assay results demonstrated that OGT silencing inhibited the migration and invasion of SKOV3 and 59M ovarian cells in vitro, while Thiamet‑G treatment promoted migration and invasion. 28259907 6 44 theme Thiamet-G 1017:1025 arg1 treatment 1027:1035 Thiamet-G treatment 1017:1035 Thiamet-G treatment 1017:1035 Furthermore, a pull‑down assay and western blot analysis demonstrated that Thiamet-G treatment enhanced RhoA activity and the phosphorylation of the Rho‑associated protein kinase (ROCK) substrate, myosin light chain (MLC), while OGT silencing attenuated RhoA activity and MLC phosphorylation. 28259907 1 45 theme functions 237:245 arg1 regulation 205:214 the regulation 201:214 the regulation of multiple cellular functions 201:245 O-GlcNAcylation is a dynamic and reversible post-translational modification associated with the regulation of multiple cellular functions. 28259907 6 46 theme light 1146:1150 arg1 MLC 1159:1161 MLC 1159:1161 MLC 1159:1161 Furthermore, a pull‑down assay and western blot analysis demonstrated that Thiamet-G treatment enhanced RhoA activity and the phosphorylation of the Rho‑associated protein kinase (ROCK) substrate, myosin light chain (MLC), while OGT silencing attenuated RhoA activity and MLC phosphorylation. 28259907 6 46 theme light 1146:1150 arg1 chain 1152:1156 myosin light chain 1139:1156 myosin light chain (MLC) 1139:1162 Furthermore, a pull‑down assay and western blot analysis demonstrated that Thiamet-G treatment enhanced RhoA activity and the phosphorylation of the Rho‑associated protein kinase (ROCK) substrate, myosin light chain (MLC), while OGT silencing attenuated RhoA activity and MLC phosphorylation. 28259907 6 46 theme light 1146:1150 arg1 substrate 1128:1136 the Rho‑associated protein kinase (ROCK) substrate 1087:1136 the Rho‑associated protein kinase (ROCK) substrate 1087:1136 Furthermore, a pull‑down assay and western blot analysis demonstrated that Thiamet-G treatment enhanced RhoA activity and the phosphorylation of the Rho‑associated protein kinase (ROCK) substrate, myosin light chain (MLC), while OGT silencing attenuated RhoA activity and MLC phosphorylation. 28259907 8 47 theme ovarian 1464:1470 arg1 cells 1479:1483 ovarian cancer cells 1464:1483 ovarian cancer cells 1464:1483 These data suggest that O‑GlcNAcylation augments the motility of ovarian cancer cells via the RhoA/ROCK/MLC signaling pathway. 28259907 7 48 from increases 1357:1365 arg1 cell 1370:1373 cell migration and invasion 1370:1396 cell migration and invasion 1370:1396 In addition, RhoA silencing via RNA interference and inhibition of ROCK activity with Y‑27632 prevented Thiamet‑G‑induced increases in cell migration and invasion. 28259907 4 49 theme RNA 675:677 arg1 interference 679:690 RNA interference 675:690 RNA interference 675:690 To investigate the effect of O-GlcNAcylation on ovarian cancer phenotypes, global O‑GlcNAc levels were decreased by OGT silencing through RNA interference and increased by inhibiting OGA activity with Thiamet‑G. 28259907 0 50 theme ovarian 57:63 arg1 cells 72:76 human ovarian cancer cells 51:76 human ovarian cancer cells 51:76 O-GlcNAcylation promotes migration and invasion in human ovarian cancer cells via the RhoA/ROCK/MLC pathway. 28259907 0 51 theme human 51:55 arg1 cells 72:76 human ovarian cancer cells 51:76 human ovarian cancer cells 51:76 O-GlcNAcylation promotes migration and invasion in human ovarian cancer cells via the RhoA/ROCK/MLC pathway. 28259907 4 52 theme O-GlcNAcylation 566:580 arg1 effect 556:561 the effect 552:561 the effect of O-GlcNAcylation on ovarian cancer phenotypes 552:609 To investigate the effect of O-GlcNAcylation on ovarian cancer phenotypes, global O‑GlcNAc levels were decreased by OGT silencing through RNA interference and increased by inhibiting OGA activity with Thiamet‑G. 28259907 7 53 dep cell 1370:1373 arg1 invasion 1389:1396 invasion 1389:1396 invasion 1389:1396 In addition, RhoA silencing via RNA interference and inhibition of ROCK activity with Y‑27632 prevented Thiamet‑G‑induced increases in cell migration and invasion. 28259907 7 53 dep cell 1370:1373 arg1 migration 1375:1383 migration 1375:1383 migration 1375:1383 In addition, RhoA silencing via RNA interference and inhibition of ROCK activity with Y‑27632 prevented Thiamet‑G‑induced increases in cell migration and invasion. 28259907 8 54 theme signaling 1507:1515 arg1 pathway 1517:1523 the RhoA/ROCK/MLC signaling pathway 1489:1523 the RhoA/ROCK/MLC signaling pathway 1489:1523 These data suggest that O‑GlcNAcylation augments the motility of ovarian cancer cells via the RhoA/ROCK/MLC signaling pathway. 28259907 3 55 theme human 523:527 arg1 cancer 529:534 human cancer 523:534 human cancer 523:534 Accumulating evidence suggests that O-GlcNAcylation is associated with the malignancy of several types of human cancer. 28259907 6 56 theme blot 985:988 arg1 analysis 990:997 western blot analysis 977:997 western blot analysis 977:997 Furthermore, a pull‑down assay and western blot analysis demonstrated that Thiamet-G treatment enhanced RhoA activity and the phosphorylation of the Rho‑associated protein kinase (ROCK) substrate, myosin light chain (MLC), while OGT silencing attenuated RhoA activity and MLC phosphorylation. 28259907 8 57 theme RhoA/ROCK/MLC 1493:1505 arg1 pathway 1517:1523 the RhoA/ROCK/MLC signaling pathway 1489:1523 the RhoA/ROCK/MLC signaling pathway 1489:1523 These data suggest that O‑GlcNAcylation augments the motility of ovarian cancer cells via the RhoA/ROCK/MLC signaling pathway. 28259907 4 58 theme OGA 720:722 arg1 activity 724:731 OGA activity 720:731 OGA activity 720:731 To investigate the effect of O-GlcNAcylation on ovarian cancer phenotypes, global O‑GlcNAc levels were decreased by OGT silencing through RNA interference and increased by inhibiting OGA activity with Thiamet‑G. 28259907 1 59 theme dynamic 130:136 arg1 modification 172:183 a dynamic and reversible post-translational modification 128:183 a dynamic and reversible post-translational modification associated with the regulation of multiple cellular functions 128:245 O-GlcNAcylation is a dynamic and reversible post-translational modification associated with the regulation of multiple cellular functions. 28259907 1 59 theme dynamic 130:136 arg1 O-GlcNAcylation 109:123 O-GlcNAcylation 109:123 O-GlcNAcylation 109:123 O-GlcNAcylation is a dynamic and reversible post-translational modification associated with the regulation of multiple cellular functions. 28259907 6 60 theme RhoA 1196:1199 arg1 activity 1201:1208 RhoA activity 1196:1208 RhoA activity 1196:1208 Furthermore, a pull‑down assay and western blot analysis demonstrated that Thiamet-G treatment enhanced RhoA activity and the phosphorylation of the Rho‑associated protein kinase (ROCK) substrate, myosin light chain (MLC), while OGT silencing attenuated RhoA activity and MLC phosphorylation. 28259907 6 61 theme protein 1106:1112 arg1 chain 1152:1156 myosin light chain 1139:1156 myosin light chain (MLC) 1139:1162 Furthermore, a pull‑down assay and western blot analysis demonstrated that Thiamet-G treatment enhanced RhoA activity and the phosphorylation of the Rho‑associated protein kinase (ROCK) substrate, myosin light chain (MLC), while OGT silencing attenuated RhoA activity and MLC phosphorylation. 28259907 6 61 theme protein 1106:1112 arg1 substrate 1128:1136 the Rho‑associated protein kinase (ROCK) substrate 1087:1136 the Rho‑associated protein kinase (ROCK) substrate 1087:1136 Furthermore, a pull‑down assay and western blot analysis demonstrated that Thiamet-G treatment enhanced RhoA activity and the phosphorylation of the Rho‑associated protein kinase (ROCK) substrate, myosin light chain (MLC), while OGT silencing attenuated RhoA activity and MLC phosphorylation. 28259907 9 62 theme cancer 1622:1627 arg1 treatment 1601:1609 treatment 1601:1609 treatment 1601:1609 Therefore, O‑GlcNAcylation may be a potential target for the diagnosis and treatment of ovarian cancer. 28259907 9 62 theme cancer 1622:1627 arg1 diagnosis 1587:1595 diagnosis 1587:1595 diagnosis 1587:1595 Therefore, O‑GlcNAcylation may be a potential target for the diagnosis and treatment of ovarian cancer. 28259907 2 63 theme β-N-acetylglucosamine 285:305 arg1 removal 265:271 removal 265:271 removal 265:271 The addition and removal of O‑Linked β-N-acetylglucosamine (O‑GlcNAc) on target proteins is catalyzed by O‑GlcNAc transferase (OGT) and O‑GlcNAcase (OGA), respectively. 28259907 2 63 theme β-N-acetylglucosamine 285:305 arg1 addition 252:259 addition 252:259 addition 252:259 The addition and removal of O‑Linked β-N-acetylglucosamine (O‑GlcNAc) on target proteins is catalyzed by O‑GlcNAc transferase (OGT) and O‑GlcNAcase (OGA), respectively. 28259907 3 64 theme types 514:518 arg1 malignancy 492:501 the malignancy 488:501 the malignancy of several types of human cancer 488:534 Accumulating evidence suggests that O-GlcNAcylation is associated with the malignancy of several types of human cancer. 28259907 3 65 theme several 506:512 arg1 types 514:518 several types 506:518 several types of human cancer 506:534 Accumulating evidence suggests that O-GlcNAcylation is associated with the malignancy of several types of human cancer. 28259907 9 66 theme potential 1562:1570 arg1 target 1572:1577 a potential target 1560:1577 a potential target for the diagnosis and treatment of ovarian cancer 1560:1627 Therefore, O‑GlcNAcylation may be a potential target for the diagnosis and treatment of ovarian cancer. 28259907 9 66 theme potential 1562:1570 arg1 O‑GlcNAcylation 1537:1551 O‑GlcNAcylation 1537:1551 O‑GlcNAcylation 1537:1551 Therefore, O‑GlcNAcylation may be a potential target for the diagnosis and treatment of ovarian cancer. 28259907 6 67 theme kinase 1114:1119 arg1 chain 1152:1156 myosin light chain 1139:1156 myosin light chain (MLC) 1139:1162 Furthermore, a pull‑down assay and western blot analysis demonstrated that Thiamet-G treatment enhanced RhoA activity and the phosphorylation of the Rho‑associated protein kinase (ROCK) substrate, myosin light chain (MLC), while OGT silencing attenuated RhoA activity and MLC phosphorylation. 28259907 6 67 theme kinase 1114:1119 arg1 substrate 1128:1136 the Rho‑associated protein kinase (ROCK) substrate 1087:1136 the Rho‑associated protein kinase (ROCK) substrate 1087:1136 Furthermore, a pull‑down assay and western blot analysis demonstrated that Thiamet-G treatment enhanced RhoA activity and the phosphorylation of the Rho‑associated protein kinase (ROCK) substrate, myosin light chain (MLC), while OGT silencing attenuated RhoA activity and MLC phosphorylation. 28259907 2 68 theme O‑Linked 276:283 arg1 O‑GlcNAc 308:315 O‑GlcNAc 308:315 O‑GlcNAc 308:315 The addition and removal of O‑Linked β-N-acetylglucosamine (O‑GlcNAc) on target proteins is catalyzed by O‑GlcNAc transferase (OGT) and O‑GlcNAcase (OGA), respectively. 28259907 2 68 theme O‑Linked 276:283 arg1 β-N-acetylglucosamine 285:305 O‑Linked β-N-acetylglucosamine 276:305 O‑Linked β-N-acetylglucosamine (O‑GlcNAc) 276:316 The addition and removal of O‑Linked β-N-acetylglucosamine (O‑GlcNAc) on target proteins is catalyzed by O‑GlcNAc transferase (OGT) and O‑GlcNAcase (OGA), respectively. 28259907 1 69 theme multiple 219:226 arg1 functions 237:245 multiple cellular functions 219:245 multiple cellular functions 219:245 O-GlcNAcylation is a dynamic and reversible post-translational modification associated with the regulation of multiple cellular functions. 28259907 1 70 theme reversible 142:151 arg1 modification 172:183 a dynamic and reversible post-translational modification 128:183 a dynamic and reversible post-translational modification associated with the regulation of multiple cellular functions 128:245 O-GlcNAcylation is a dynamic and reversible post-translational modification associated with the regulation of multiple cellular functions. 28259907 1 70 theme reversible 142:151 arg1 O-GlcNAcylation 109:123 O-GlcNAcylation 109:123 O-GlcNAcylation 109:123 O-GlcNAcylation is a dynamic and reversible post-translational modification associated with the regulation of multiple cellular functions. 28259907 4 71 theme OGT 653:655 arg1 silencing 657:665 OGT silencing 653:665 OGT silencing 653:665 To investigate the effect of O-GlcNAcylation on ovarian cancer phenotypes, global O‑GlcNAc levels were decreased by OGT silencing through RNA interference and increased by inhibiting OGA activity with Thiamet‑G. 28259907 0 72 theme cancer 65:70 arg1 cells 72:76 human ovarian cancer cells 51:76 human ovarian cancer cells 51:76 O-GlcNAcylation promotes migration and invasion in human ovarian cancer cells via the RhoA/ROCK/MLC pathway. 28259907 6 73 theme western 977:983 arg1 analysis 990:997 western blot analysis 977:997 western blot analysis 977:997 Furthermore, a pull‑down assay and western blot analysis demonstrated that Thiamet-G treatment enhanced RhoA activity and the phosphorylation of the Rho‑associated protein kinase (ROCK) substrate, myosin light chain (MLC), while OGT silencing attenuated RhoA activity and MLC phosphorylation. 28259907 7 74 theme Thiamet‑G‑induced 1339:1355 arg1 increases 1357:1365 Thiamet‑G‑induced increases 1339:1365 Thiamet‑G‑induced increases in cell migration and invasion 1339:1396 In addition, RhoA silencing via RNA interference and inhibition of ROCK activity with Y‑27632 prevented Thiamet‑G‑induced increases in cell migration and invasion. 28259907 1 75 theme post-translational 153:170 arg1 modification 172:183 a dynamic and reversible post-translational modification 128:183 a dynamic and reversible post-translational modification associated with the regulation of multiple cellular functions 128:245 O-GlcNAcylation is a dynamic and reversible post-translational modification associated with the regulation of multiple cellular functions. 28259907 1 75 theme post-translational 153:170 arg1 O-GlcNAcylation 109:123 O-GlcNAcylation 109:123 O-GlcNAcylation 109:123 O-GlcNAcylation is a dynamic and reversible post-translational modification associated with the regulation of multiple cellular functions. 27669760 0 0 theme Oxidative 99:107 arg1 Stress 109:114 Oxidative Stress 99:114 Oxidative Stress 99:114 Combined Antibody/Lectin Enrichment Identifies Extensive Changes in the O-GlcNAc Sub-proteome upon Oxidative Stress. 27669760 4 1 theme Isotope 723:729 arg1 Labeling 731:738 Stable Isotope Labeling 716:738 Stable Isotope Labeling of Amino Acids in Cell Culture (SILAC) 716:777 We achieved this goal by employing Stable Isotope Labeling of Amino Acids in Cell Culture (SILAC) and a novel "G5-lectibody" immunoprecipitation strategy that combines four O-GlcNAc-specific antibodies (CTD110.6, RL2, HGAC39, and HGAC85) and the lectin WGA. 27669760 7 2 theme RNA 1580:1582 arg1 biogenesis 1584:1593 RNA biogenesis 1580:1593 RNA biogenesis 1580:1593 Analysis of proteins with altered glycosylation suggests that stress-induced changes in O-GlcNAcylation cluster into pathways known to regulate the cell's response to injury and include protein folding, transcriptional regulation, epigenetics, and proteins involved in RNA biogenesis. 27669760 6 3 theme O-GlcNAcylation 1272:1286 arg1 status 1288:1293 the O-GlcNAcylation status 1268:1293 the O-GlcNAcylation status of 24 proteins 1268:1308 Hundreds of proteins that were identified demonstrated increased (>250) or decreased (>110) association with the G5-lectibody column upon oxidative stress, of which we validated the O-GlcNAcylation status of 24 proteins. 27669760 4 4 theme Stable 716:721 arg1 Labeling 731:738 Stable Isotope Labeling 716:738 Stable Isotope Labeling of Amino Acids in Cell Culture (SILAC) 716:777 We achieved this goal by employing Stable Isotope Labeling of Amino Acids in Cell Culture (SILAC) and a novel "G5-lectibody" immunoprecipitation strategy that combines four O-GlcNAc-specific antibodies (CTD110.6, RL2, HGAC39, and HGAC85) and the lectin WGA. 27669760 8 5 theme tissue 1730:1735 arg1 survival 1737:1744 cell and tissue survival 1721:1744 survival 1737:1744 Together, these data suggest that stress-induced O-GlcNAcylation regulates numerous and diverse cellular pathways to promote cell and tissue survival. 27669760 6 6 with association 1182:1192 arg1 column 1216:1221 the G5-lectibody column 1199:1221 the G5-lectibody column 1199:1221 Hundreds of proteins that were identified demonstrated increased (>250) or decreased (>110) association with the G5-lectibody column upon oxidative stress, of which we validated the O-GlcNAcylation status of 24 proteins. 27669760 5 7 theme basic 989:993 arg1 RPLC-MS/MS 1033:1042 basic reversed phase chromatography and C18 RPLC-MS/MS 989:1042 basic reversed phase chromatography and C18 RPLC-MS/MS 989:1042 Using the G5-lectibody column in combination with basic reversed phase chromatography and C18 RPLC-MS/MS, 990 proteins were identified and quantified. 27669760 7 8 theme stress-induced 1373:1386 arg1 changes 1388:1394 stress-induced changes 1373:1394 stress-induced changes in O-GlcNAcylation 1373:1413 Analysis of proteins with altered glycosylation suggests that stress-induced changes in O-GlcNAcylation cluster into pathways known to regulate the cell's response to injury and include protein folding, transcriptional regulation, epigenetics, and proteins involved in RNA biogenesis. 27669760 3 9 theme acute 575:579 arg1 H2O2 599:602 H2O2 599:602 H2O2 599:602 The aim of this study was to identify proteins that are differentially O-GlcNAcylated upon acute oxidative stress (H2O2) to provide insight into the mechanisms by which O-GlcNAc promotes survival. 27669760 3 9 theme acute 575:579 arg1 stress 591:596 acute oxidative stress 575:596 acute oxidative stress (H2O2) 575:603 The aim of this study was to identify proteins that are differentially O-GlcNAcylated upon acute oxidative stress (H2O2) to provide insight into the mechanisms by which O-GlcNAc promotes survival. 27669760 5 10 from column 962:967 arg1 combination 972:982 combination 972:982 combination with basic reversed phase chromatography and C18 RPLC-MS/MS 972:1042 Using the G5-lectibody column in combination with basic reversed phase chromatography and C18 RPLC-MS/MS, 990 proteins were identified and quantified. 27669760 6 11 dep increased 1145:1153 arg1 >250 1156:1159 >250 1156:1159 >250 1156:1159 Hundreds of proteins that were identified demonstrated increased (>250) or decreased (>110) association with the G5-lectibody column upon oxidative stress, of which we validated the O-GlcNAcylation status of 24 proteins. 27669760 3 12 theme oxidative 581:589 arg1 H2O2 599:602 H2O2 599:602 H2O2 599:602 The aim of this study was to identify proteins that are differentially O-GlcNAcylated upon acute oxidative stress (H2O2) to provide insight into the mechanisms by which O-GlcNAc promotes survival. 27669760 3 12 theme oxidative 581:589 arg1 stress 591:596 acute oxidative stress 575:596 acute oxidative stress (H2O2) 575:603 The aim of this study was to identify proteins that are differentially O-GlcNAcylated upon acute oxidative stress (H2O2) to provide insight into the mechanisms by which O-GlcNAc promotes survival. 27669760 8 13 theme numerous 1671:1678 arg1 pathways 1701:1708 numerous and diverse cellular pathways 1671:1708 numerous and diverse cellular pathways 1671:1708 Together, these data suggest that stress-induced O-GlcNAcylation regulates numerous and diverse cellular pathways to promote cell and tissue survival. 27669760 4 14 theme O-GlcNAc-specific 854:870 arg1 antibodies 872:881 four O-GlcNAc-specific antibodies 849:881 four O-GlcNAc-specific antibodies (CTD110.6, RL2, HGAC39, and HGAC85) 849:917 We achieved this goal by employing Stable Isotope Labeling of Amino Acids in Cell Culture (SILAC) and a novel "G5-lectibody" immunoprecipitation strategy that combines four O-GlcNAc-specific antibodies (CTD110.6, RL2, HGAC39, and HGAC85) and the lectin WGA. 27669760 4 14 theme O-GlcNAc-specific 854:870 arg1 HGAC39 899:904 HGAC39 899:904 HGAC39 899:904 We achieved this goal by employing Stable Isotope Labeling of Amino Acids in Cell Culture (SILAC) and a novel "G5-lectibody" immunoprecipitation strategy that combines four O-GlcNAc-specific antibodies (CTD110.6, RL2, HGAC39, and HGAC85) and the lectin WGA. 27669760 4 14 theme O-GlcNAc-specific 854:870 arg1 HGAC85 911:916 HGAC85 911:916 HGAC85 911:916 We achieved this goal by employing Stable Isotope Labeling of Amino Acids in Cell Culture (SILAC) and a novel "G5-lectibody" immunoprecipitation strategy that combines four O-GlcNAc-specific antibodies (CTD110.6, RL2, HGAC39, and HGAC85) and the lectin WGA. 27669760 4 14 theme O-GlcNAc-specific 854:870 arg1 RL2 894:896 RL2 894:896 RL2 894:896 We achieved this goal by employing Stable Isotope Labeling of Amino Acids in Cell Culture (SILAC) and a novel "G5-lectibody" immunoprecipitation strategy that combines four O-GlcNAc-specific antibodies (CTD110.6, RL2, HGAC39, and HGAC85) and the lectin WGA. 27669760 4 14 theme O-GlcNAc-specific 854:870 arg1 CTD110.6 884:891 CTD110.6 884:891 CTD110.6 884:891 We achieved this goal by employing Stable Isotope Labeling of Amino Acids in Cell Culture (SILAC) and a novel "G5-lectibody" immunoprecipitation strategy that combines four O-GlcNAc-specific antibodies (CTD110.6, RL2, HGAC39, and HGAC85) and the lectin WGA. 27669760 6 15 dep decreased 1165:1173 arg1 >110 1176:1179 >110 1176:1179 >110 1176:1179 Hundreds of proteins that were identified demonstrated increased (>250) or decreased (>110) association with the G5-lectibody column upon oxidative stress, of which we validated the O-GlcNAcylation status of 24 proteins. 27669760 7 16 theme altered 1337:1343 arg1 glycosylation 1345:1357 altered glycosylation 1337:1357 altered glycosylation 1337:1357 Analysis of proteins with altered glycosylation suggests that stress-induced changes in O-GlcNAcylation cluster into pathways known to regulate the cell's response to injury and include protein folding, transcriptional regulation, epigenetics, and proteins involved in RNA biogenesis. 27669760 7 17 theme proteins 1323:1330 arg1 Analysis 1311:1318 Analysis 1311:1318 Analysis of proteins with altered glycosylation 1311:1357 Analysis of proteins with altered glycosylation suggests that stress-induced changes in O-GlcNAcylation cluster into pathways known to regulate the cell's response to injury and include protein folding, transcriptional regulation, epigenetics, and proteins involved in RNA biogenesis. 27669760 0 18 from Changes 57:63 arg1 Sub-proteome 81:92 the O-GlcNAc Sub-proteome 68:92 the O-GlcNAc Sub-proteome 68:92 Combined Antibody/Lectin Enrichment Identifies Extensive Changes in the O-GlcNAc Sub-proteome upon Oxidative Stress. 27669760 4 19 dep antibodies 872:881 arg1 antibodies 872:881 four O-GlcNAc-specific antibodies 849:881 four O-GlcNAc-specific antibodies (CTD110.6, RL2, HGAC39, and HGAC85) 849:917 We achieved this goal by employing Stable Isotope Labeling of Amino Acids in Cell Culture (SILAC) and a novel "G5-lectibody" immunoprecipitation strategy that combines four O-GlcNAc-specific antibodies (CTD110.6, RL2, HGAC39, and HGAC85) and the lectin WGA. 27669760 4 19 dep antibodies 872:881 arg1 HGAC39 899:904 HGAC39 899:904 HGAC39 899:904 We achieved this goal by employing Stable Isotope Labeling of Amino Acids in Cell Culture (SILAC) and a novel "G5-lectibody" immunoprecipitation strategy that combines four O-GlcNAc-specific antibodies (CTD110.6, RL2, HGAC39, and HGAC85) and the lectin WGA. 27669760 4 19 dep antibodies 872:881 arg1 HGAC85 911:916 HGAC85 911:916 HGAC85 911:916 We achieved this goal by employing Stable Isotope Labeling of Amino Acids in Cell Culture (SILAC) and a novel "G5-lectibody" immunoprecipitation strategy that combines four O-GlcNAc-specific antibodies (CTD110.6, RL2, HGAC39, and HGAC85) and the lectin WGA. 27669760 4 19 dep antibodies 872:881 arg1 RL2 894:896 RL2 894:896 RL2 894:896 We achieved this goal by employing Stable Isotope Labeling of Amino Acids in Cell Culture (SILAC) and a novel "G5-lectibody" immunoprecipitation strategy that combines four O-GlcNAc-specific antibodies (CTD110.6, RL2, HGAC39, and HGAC85) and the lectin WGA. 27669760 4 19 dep antibodies 872:881 arg1 CTD110.6 884:891 CTD110.6 884:891 CTD110.6 884:891 We achieved this goal by employing Stable Isotope Labeling of Amino Acids in Cell Culture (SILAC) and a novel "G5-lectibody" immunoprecipitation strategy that combines four O-GlcNAc-specific antibodies (CTD110.6, RL2, HGAC39, and HGAC85) and the lectin WGA. 27669760 2 20 theme proteins 417:424 arg1 modification 371:382 the O-GlcNAc modification 358:382 the O-GlcNAc modification 358:382 Upon exposure to stress and injury, cells and tissues increase the O-GlcNAc modification, or O-GlcNAcylation, of numerous proteins promoting the cellular stress response and thus survival. 27669760 2 20 theme proteins 417:424 arg1 O-GlcNAcylation 388:402 O-GlcNAcylation 388:402 O-GlcNAcylation 388:402 Upon exposure to stress and injury, cells and tissues increase the O-GlcNAc modification, or O-GlcNAcylation, of numerous proteins promoting the cellular stress response and thus survival. 27669760 0 21 theme Antibody/Lectin 9:23 arg1 Enrichment 25:34 Combined Antibody/Lectin Enrichment 0:34 Combined Antibody/Lectin Enrichment 0:34 Combined Antibody/Lectin Enrichment Identifies Extensive Changes in the O-GlcNAc Sub-proteome upon Oxidative Stress. 27669760 7 22 theme protein 1497:1503 arg1 folding 1505:1511 protein folding 1497:1511 protein folding 1497:1511 Analysis of proteins with altered glycosylation suggests that stress-induced changes in O-GlcNAcylation cluster into pathways known to regulate the cell's response to injury and include protein folding, transcriptional regulation, epigenetics, and proteins involved in RNA biogenesis. 27669760 4 23 theme Cell 758:761 arg1 Culture 763:769 Cell Culture 758:769 Cell Culture (SILAC) 758:777 We achieved this goal by employing Stable Isotope Labeling of Amino Acids in Cell Culture (SILAC) and a novel "G5-lectibody" immunoprecipitation strategy that combines four O-GlcNAc-specific antibodies (CTD110.6, RL2, HGAC39, and HGAC85) and the lectin WGA. 27669760 4 23 theme Cell 758:761 arg1 SILAC 772:776 SILAC 772:776 SILAC 772:776 We achieved this goal by employing Stable Isotope Labeling of Amino Acids in Cell Culture (SILAC) and a novel "G5-lectibody" immunoprecipitation strategy that combines four O-GlcNAc-specific antibodies (CTD110.6, RL2, HGAC39, and HGAC85) and the lectin WGA. 27669760 2 24 theme numerous 408:415 arg1 proteins 417:424 numerous proteins 408:424 numerous proteins promoting the cellular stress response and thus survival 408:481 Upon exposure to stress and injury, cells and tissues increase the O-GlcNAc modification, or O-GlcNAcylation, of numerous proteins promoting the cellular stress response and thus survival. 27669760 0 25 theme Combined 0:7 arg1 Enrichment 25:34 Combined Antibody/Lectin Enrichment 0:34 Combined Antibody/Lectin Enrichment 0:34 Combined Antibody/Lectin Enrichment Identifies Extensive Changes in the O-GlcNAc Sub-proteome upon Oxidative Stress. 27669760 7 26 theme transcriptional 1514:1528 arg1 regulation 1530:1539 transcriptional regulation 1514:1539 transcriptional regulation 1514:1539 Analysis of proteins with altered glycosylation suggests that stress-induced changes in O-GlcNAcylation cluster into pathways known to regulate the cell's response to injury and include protein folding, transcriptional regulation, epigenetics, and proteins involved in RNA biogenesis. 27669760 7 27 gly glycosylation 1345:1357 arg1 proteins 1323:1330 proteins 1323:1330 proteins with altered glycosylation 1323:1357 Analysis of proteins with altered glycosylation suggests that stress-induced changes in O-GlcNAcylation cluster into pathways known to regulate the cell's response to injury and include protein folding, transcriptional regulation, epigenetics, and proteins involved in RNA biogenesis. 27669760 5 28 theme reversed 995:1002 arg1 chromatography 1010:1023 reversed phase chromatography 995:1023 reversed phase chromatography 995:1023 Using the G5-lectibody column in combination with basic reversed phase chromatography and C18 RPLC-MS/MS, 990 proteins were identified and quantified. 27669760 1 29 theme O-Linked 117:124 arg1 modification 194:205 a dynamic post-translational modification 165:205 a dynamic post-translational modification that modifies and regulates over 3000 nuclear, cytoplasmic, and mitochondrial proteins 165:292 O-Linked N-acetyl-β-d-glucosamine (O-GlcNAc) is a dynamic post-translational modification that modifies and regulates over 3000 nuclear, cytoplasmic, and mitochondrial proteins. 27669760 1 29 theme O-Linked 117:124 arg1 O-GlcNAc 152:159 O-GlcNAc 152:159 O-GlcNAc 152:159 O-Linked N-acetyl-β-d-glucosamine (O-GlcNAc) is a dynamic post-translational modification that modifies and regulates over 3000 nuclear, cytoplasmic, and mitochondrial proteins. 27669760 1 29 theme O-Linked 117:124 arg1 N-acetyl-β-d-glucosamine 126:149 O-Linked N-acetyl-β-d-glucosamine 117:149 O-Linked N-acetyl-β-d-glucosamine (O-GlcNAc) 117:160 O-Linked N-acetyl-β-d-glucosamine (O-GlcNAc) is a dynamic post-translational modification that modifies and regulates over 3000 nuclear, cytoplasmic, and mitochondrial proteins. 27669760 7 30 from changes 1388:1394 arg1 O-GlcNAcylation 1399:1413 O-GlcNAcylation 1399:1413 O-GlcNAcylation 1399:1413 Analysis of proteins with altered glycosylation suggests that stress-induced changes in O-GlcNAcylation cluster into pathways known to regulate the cell's response to injury and include protein folding, transcriptional regulation, epigenetics, and proteins involved in RNA biogenesis. 27669760 5 31 theme G5-lectibody 949:960 arg1 column 962:967 the G5-lectibody column 945:967 the G5-lectibody column in combination with basic reversed phase chromatography and C18 RPLC-MS/MS 945:1042 Using the G5-lectibody column in combination with basic reversed phase chromatography and C18 RPLC-MS/MS, 990 proteins were identified and quantified. 27669760 2 32 theme stress 449:454 arg1 response 456:463 the cellular stress response 436:463 the cellular stress response 436:463 Upon exposure to stress and injury, cells and tissues increase the O-GlcNAc modification, or O-GlcNAcylation, of numerous proteins promoting the cellular stress response and thus survival. 27669760 4 33 theme lectin 927:932 arg1 WGA 934:936 the lectin WGA 923:936 the lectin WGA 923:936 We achieved this goal by employing Stable Isotope Labeling of Amino Acids in Cell Culture (SILAC) and a novel "G5-lectibody" immunoprecipitation strategy that combines four O-GlcNAc-specific antibodies (CTD110.6, RL2, HGAC39, and HGAC85) and the lectin WGA. 27669760 1 34 theme nuclear 245:251 arg1 proteins 285:292 3000 nuclear, cytoplasmic, and mitochondrial proteins 240:292 3000 nuclear, cytoplasmic, and mitochondrial proteins 240:292 O-Linked N-acetyl-β-d-glucosamine (O-GlcNAc) is a dynamic post-translational modification that modifies and regulates over 3000 nuclear, cytoplasmic, and mitochondrial proteins. 27669760 5 35 theme chromatography 1010:1023 arg1 RPLC-MS/MS 1033:1042 basic reversed phase chromatography and C18 RPLC-MS/MS 989:1042 basic reversed phase chromatography and C18 RPLC-MS/MS 989:1042 Using the G5-lectibody column in combination with basic reversed phase chromatography and C18 RPLC-MS/MS, 990 proteins were identified and quantified. 27669760 4 36 from Labeling 731:738 arg1 Culture 763:769 Cell Culture 758:769 Cell Culture (SILAC) 758:777 We achieved this goal by employing Stable Isotope Labeling of Amino Acids in Cell Culture (SILAC) and a novel "G5-lectibody" immunoprecipitation strategy that combines four O-GlcNAc-specific antibodies (CTD110.6, RL2, HGAC39, and HGAC85) and the lectin WGA. 27669760 4 36 from Labeling 731:738 arg1 SILAC 772:776 SILAC 772:776 SILAC 772:776 We achieved this goal by employing Stable Isotope Labeling of Amino Acids in Cell Culture (SILAC) and a novel "G5-lectibody" immunoprecipitation strategy that combines four O-GlcNAc-specific antibodies (CTD110.6, RL2, HGAC39, and HGAC85) and the lectin WGA. 27669760 2 37 theme cellular 440:447 arg1 response 456:463 the cellular stress response 436:463 the cellular stress response 436:463 Upon exposure to stress and injury, cells and tissues increase the O-GlcNAc modification, or O-GlcNAcylation, of numerous proteins promoting the cellular stress response and thus survival. 27669760 0 38 theme Extensive 47:55 arg1 Changes 57:63 Extensive Changes 47:63 Extensive Changes in the O-GlcNAc Sub-proteome upon Oxidative Stress 47:114 Combined Antibody/Lectin Enrichment Identifies Extensive Changes in the O-GlcNAc Sub-proteome upon Oxidative Stress. 27669760 5 39 with combination 972:982 arg1 RPLC-MS/MS 1033:1042 basic reversed phase chromatography and C18 RPLC-MS/MS 989:1042 basic reversed phase chromatography and C18 RPLC-MS/MS 989:1042 Using the G5-lectibody column in combination with basic reversed phase chromatography and C18 RPLC-MS/MS, 990 proteins were identified and quantified. 27669760 4 40 theme immunoprecipitation 806:824 arg1 strategy 826:833 a novel "G5-lectibody" immunoprecipitation strategy 783:833 a novel "G5-lectibody" immunoprecipitation strategy that combines four O-GlcNAc-specific antibodies (CTD110.6, RL2, HGAC39, and HGAC85) and the lectin WGA 783:936 We achieved this goal by employing Stable Isotope Labeling of Amino Acids in Cell Culture (SILAC) and a novel "G5-lectibody" immunoprecipitation strategy that combines four O-GlcNAc-specific antibodies (CTD110.6, RL2, HGAC39, and HGAC85) and the lectin WGA. 27669760 5 41 theme C18 1029:1031 arg1 RPLC-MS/MS 1033:1042 basic reversed phase chromatography and C18 RPLC-MS/MS 989:1042 basic reversed phase chromatography and C18 RPLC-MS/MS 989:1042 Using the G5-lectibody column in combination with basic reversed phase chromatography and C18 RPLC-MS/MS, 990 proteins were identified and quantified. 27669760 6 42 theme increased 1145:1153 arg1 association 1182:1192 increased (>250) or decreased (>110) association 1145:1192 increased (>250) or decreased (>110) association with the G5-lectibody column 1145:1221 Hundreds of proteins that were identified demonstrated increased (>250) or decreased (>110) association with the G5-lectibody column upon oxidative stress, of which we validated the O-GlcNAcylation status of 24 proteins. 27669760 6 43 theme proteins 1301:1308 arg1 status 1288:1293 the O-GlcNAcylation status 1268:1293 the O-GlcNAcylation status of 24 proteins 1268:1308 Hundreds of proteins that were identified demonstrated increased (>250) or decreased (>110) association with the G5-lectibody column upon oxidative stress, of which we validated the O-GlcNAcylation status of 24 proteins. 27669760 4 44 from strategy 826:833 arg1 Culture 763:769 Cell Culture 758:769 Cell Culture (SILAC) 758:777 We achieved this goal by employing Stable Isotope Labeling of Amino Acids in Cell Culture (SILAC) and a novel "G5-lectibody" immunoprecipitation strategy that combines four O-GlcNAc-specific antibodies (CTD110.6, RL2, HGAC39, and HGAC85) and the lectin WGA. 27669760 4 44 from strategy 826:833 arg1 SILAC 772:776 SILAC 772:776 SILAC 772:776 We achieved this goal by employing Stable Isotope Labeling of Amino Acids in Cell Culture (SILAC) and a novel "G5-lectibody" immunoprecipitation strategy that combines four O-GlcNAc-specific antibodies (CTD110.6, RL2, HGAC39, and HGAC85) and the lectin WGA. 27669760 2 45 theme O-GlcNAc 362:369 arg1 modification 371:382 the O-GlcNAc modification 358:382 the O-GlcNAc modification 358:382 Upon exposure to stress and injury, cells and tissues increase the O-GlcNAc modification, or O-GlcNAcylation, of numerous proteins promoting the cellular stress response and thus survival. 27669760 8 46 theme cellular 1692:1699 arg1 pathways 1701:1708 numerous and diverse cellular pathways 1671:1708 numerous and diverse cellular pathways 1671:1708 Together, these data suggest that stress-induced O-GlcNAcylation regulates numerous and diverse cellular pathways to promote cell and tissue survival. 27669760 5 47 theme phase 1004:1008 arg1 chromatography 1010:1023 reversed phase chromatography 995:1023 reversed phase chromatography 995:1023 Using the G5-lectibody column in combination with basic reversed phase chromatography and C18 RPLC-MS/MS, 990 proteins were identified and quantified. 27669760 7 48 with proteins 1323:1330 arg1 glycosylation 1345:1357 altered glycosylation 1337:1357 altered glycosylation 1337:1357 Analysis of proteins with altered glycosylation suggests that stress-induced changes in O-GlcNAcylation cluster into pathways known to regulate the cell's response to injury and include protein folding, transcriptional regulation, epigenetics, and proteins involved in RNA biogenesis. 27669760 5 49 theme 990 1045:1047 arg1 proteins 1049:1056 990 proteins 1045:1056 990 proteins 1045:1056 Using the G5-lectibody column in combination with basic reversed phase chromatography and C18 RPLC-MS/MS, 990 proteins were identified and quantified. 27669760 6 50 theme G5-lectibody 1203:1214 arg1 column 1216:1221 the G5-lectibody column 1199:1221 the G5-lectibody column 1199:1221 Hundreds of proteins that were identified demonstrated increased (>250) or decreased (>110) association with the G5-lectibody column upon oxidative stress, of which we validated the O-GlcNAcylation status of 24 proteins. 27669760 6 51 theme oxidative 1228:1236 arg1 stress 1238:1243 oxidative stress 1228:1243 oxidative stress 1228:1243 Hundreds of proteins that were identified demonstrated increased (>250) or decreased (>110) association with the G5-lectibody column upon oxidative stress, of which we validated the O-GlcNAcylation status of 24 proteins. 27669760 3 52 theme study 500:504 arg1 aim 488:490 The aim 484:490 The aim of this study 484:504 The aim of this study was to identify proteins that are differentially O-GlcNAcylated upon acute oxidative stress (H2O2) to provide insight into the mechanisms by which O-GlcNAc promotes survival. 27669760 8 53 theme diverse 1684:1690 arg1 pathways 1701:1708 numerous and diverse cellular pathways 1671:1708 numerous and diverse cellular pathways 1671:1708 Together, these data suggest that stress-induced O-GlcNAcylation regulates numerous and diverse cellular pathways to promote cell and tissue survival. 27669760 1 54 theme cytoplasmic 254:264 arg1 proteins 285:292 3000 nuclear, cytoplasmic, and mitochondrial proteins 240:292 3000 nuclear, cytoplasmic, and mitochondrial proteins 240:292 O-Linked N-acetyl-β-d-glucosamine (O-GlcNAc) is a dynamic post-translational modification that modifies and regulates over 3000 nuclear, cytoplasmic, and mitochondrial proteins. 27669760 6 55 theme decreased 1165:1173 arg1 association 1182:1192 increased (>250) or decreased (>110) association 1145:1192 increased (>250) or decreased (>110) association with the G5-lectibody column 1145:1221 Hundreds of proteins that were identified demonstrated increased (>250) or decreased (>110) association with the G5-lectibody column upon oxidative stress, of which we validated the O-GlcNAcylation status of 24 proteins. 27669760 4 56 theme novel 785:789 arg1 strategy 826:833 a novel "G5-lectibody" immunoprecipitation strategy 783:833 a novel "G5-lectibody" immunoprecipitation strategy that combines four O-GlcNAc-specific antibodies (CTD110.6, RL2, HGAC39, and HGAC85) and the lectin WGA 783:936 We achieved this goal by employing Stable Isotope Labeling of Amino Acids in Cell Culture (SILAC) and a novel "G5-lectibody" immunoprecipitation strategy that combines four O-GlcNAc-specific antibodies (CTD110.6, RL2, HGAC39, and HGAC85) and the lectin WGA. 27669760 4 57 theme Amino 743:747 arg1 Acids 749:753 Amino Acids 743:753 Amino Acids 743:753 We achieved this goal by employing Stable Isotope Labeling of Amino Acids in Cell Culture (SILAC) and a novel "G5-lectibody" immunoprecipitation strategy that combines four O-GlcNAc-specific antibodies (CTD110.6, RL2, HGAC39, and HGAC85) and the lectin WGA. 27669760 4 58 theme Acids 749:753 arg1 strategy 826:833 a novel "G5-lectibody" immunoprecipitation strategy 783:833 a novel "G5-lectibody" immunoprecipitation strategy that combines four O-GlcNAc-specific antibodies (CTD110.6, RL2, HGAC39, and HGAC85) and the lectin WGA 783:936 We achieved this goal by employing Stable Isotope Labeling of Amino Acids in Cell Culture (SILAC) and a novel "G5-lectibody" immunoprecipitation strategy that combines four O-GlcNAc-specific antibodies (CTD110.6, RL2, HGAC39, and HGAC85) and the lectin WGA. 27669760 4 58 theme Acids 749:753 arg1 Labeling 731:738 Stable Isotope Labeling 716:738 Stable Isotope Labeling of Amino Acids in Cell Culture (SILAC) 716:777 We achieved this goal by employing Stable Isotope Labeling of Amino Acids in Cell Culture (SILAC) and a novel "G5-lectibody" immunoprecipitation strategy that combines four O-GlcNAc-specific antibodies (CTD110.6, RL2, HGAC39, and HGAC85) and the lectin WGA. 27669760 6 59 theme proteins 1102:1109 arg1 Hundreds 1090:1097 Hundreds 1090:1097 Hundreds of proteins that were identified 1090:1130 Hundreds of proteins that were identified demonstrated increased (>250) or decreased (>110) association with the G5-lectibody column upon oxidative stress, of which we validated the O-GlcNAcylation status of 24 proteins. 27669760 4 60 theme " 804:804 arg1 strategy 826:833 a novel "G5-lectibody" immunoprecipitation strategy 783:833 a novel "G5-lectibody" immunoprecipitation strategy that combines four O-GlcNAc-specific antibodies (CTD110.6, RL2, HGAC39, and HGAC85) and the lectin WGA 783:936 We achieved this goal by employing Stable Isotope Labeling of Amino Acids in Cell Culture (SILAC) and a novel "G5-lectibody" immunoprecipitation strategy that combines four O-GlcNAc-specific antibodies (CTD110.6, RL2, HGAC39, and HGAC85) and the lectin WGA. 27669760 2 61 mod modification 371:382 arg1 proteins 417:424 numerous proteins 408:424 numerous proteins promoting the cellular stress response and thus survival 408:481 Upon exposure to stress and injury, cells and tissues increase the O-GlcNAc modification, or O-GlcNAcylation, of numerous proteins promoting the cellular stress response and thus survival. 27669760 2 61 mod modification 371:382 arg3 O-GlcNAc 362:369 the O-GlcNAc modification 358:382 the O-GlcNAc modification 358:382 Upon exposure to stress and injury, cells and tissues increase the O-GlcNAc modification, or O-GlcNAcylation, of numerous proteins promoting the cellular stress response and thus survival. 27669760 8 62 theme stress-induced 1630:1643 arg1 O-GlcNAcylation 1645:1659 stress-induced O-GlcNAcylation 1630:1659 stress-induced O-GlcNAcylation 1630:1659 Together, these data suggest that stress-induced O-GlcNAcylation regulates numerous and diverse cellular pathways to promote cell and tissue survival. 27669760 0 63 theme O-GlcNAc 72:79 arg1 Sub-proteome 81:92 the O-GlcNAc Sub-proteome 68:92 the O-GlcNAc Sub-proteome 68:92 Combined Antibody/Lectin Enrichment Identifies Extensive Changes in the O-GlcNAc Sub-proteome upon Oxidative Stress. 27669760 1 64 theme post-translational 175:192 arg1 N-acetyl-β-d-glucosamine 126:149 O-Linked N-acetyl-β-d-glucosamine 117:149 O-Linked N-acetyl-β-d-glucosamine (O-GlcNAc) 117:160 O-Linked N-acetyl-β-d-glucosamine (O-GlcNAc) is a dynamic post-translational modification that modifies and regulates over 3000 nuclear, cytoplasmic, and mitochondrial proteins. 27669760 1 64 theme post-translational 175:192 arg1 modification 194:205 a dynamic post-translational modification 165:205 a dynamic post-translational modification that modifies and regulates over 3000 nuclear, cytoplasmic, and mitochondrial proteins 165:292 O-Linked N-acetyl-β-d-glucosamine (O-GlcNAc) is a dynamic post-translational modification that modifies and regulates over 3000 nuclear, cytoplasmic, and mitochondrial proteins. 27669760 4 65 theme G5-lectibody 792:803 arg1 strategy 826:833 a novel "G5-lectibody" immunoprecipitation strategy 783:833 a novel "G5-lectibody" immunoprecipitation strategy that combines four O-GlcNAc-specific antibodies (CTD110.6, RL2, HGAC39, and HGAC85) and the lectin WGA 783:936 We achieved this goal by employing Stable Isotope Labeling of Amino Acids in Cell Culture (SILAC) and a novel "G5-lectibody" immunoprecipitation strategy that combines four O-GlcNAc-specific antibodies (CTD110.6, RL2, HGAC39, and HGAC85) and the lectin WGA. 27669760 1 66 theme dynamic 167:173 arg1 N-acetyl-β-d-glucosamine 126:149 O-Linked N-acetyl-β-d-glucosamine 117:149 O-Linked N-acetyl-β-d-glucosamine (O-GlcNAc) 117:160 O-Linked N-acetyl-β-d-glucosamine (O-GlcNAc) is a dynamic post-translational modification that modifies and regulates over 3000 nuclear, cytoplasmic, and mitochondrial proteins. 27669760 1 66 theme dynamic 167:173 arg1 modification 194:205 a dynamic post-translational modification 165:205 a dynamic post-translational modification that modifies and regulates over 3000 nuclear, cytoplasmic, and mitochondrial proteins 165:292 O-Linked N-acetyl-β-d-glucosamine (O-GlcNAc) is a dynamic post-translational modification that modifies and regulates over 3000 nuclear, cytoplasmic, and mitochondrial proteins. 27669760 8 67 theme cell 1721:1724 arg1 survival 1737:1744 cell and tissue survival 1721:1744 survival 1737:1744 Together, these data suggest that stress-induced O-GlcNAcylation regulates numerous and diverse cellular pathways to promote cell and tissue survival. 27669760 1 68 theme mitochondrial 271:283 arg1 proteins 285:292 3000 nuclear, cytoplasmic, and mitochondrial proteins 240:292 3000 nuclear, cytoplasmic, and mitochondrial proteins 240:292 O-Linked N-acetyl-β-d-glucosamine (O-GlcNAc) is a dynamic post-translational modification that modifies and regulates over 3000 nuclear, cytoplasmic, and mitochondrial proteins. 24898611 3 0 theme serum-free 749:758 arg1 monolayer 760:768 serum-free monolayer 749:768 serum-free monolayer 749:768 Here, we demonstrate that the specific inhibition of O-GlcNAc hydrolase (Oga) causes increased levels of protein O-GlcNAcylation and impairs differentiation of mouse ESCs both in serum-free monolayer and in embryoid bodies (EBs). 24898611 5 1 theme markers 1103:1109 arg1 expression 1063:1072 expression 1063:1072 expression of mesodermal and endodermal markers 1063:1109 In EBs, expression of mesodermal and endodermal markers is also delayed. 24898611 5 2 theme mesodermal 1077:1086 arg1 markers 1103:1109 mesodermal and endodermal markers 1077:1109 mesodermal and endodermal markers 1077:1109 In EBs, expression of mesodermal and endodermal markers is also delayed. 24898611 1 3 theme multiple 245:252 arg1 pathways 264:271 multiple signaling pathways 245:271 multiple signaling pathways 245:271 The differentiation of mouse embryonic stem cells (ESCs) is controlled by the interaction of multiple signaling pathways, typically mediated by post-translational protein modifications. 24898611 0 4 theme ESC 81:83 arg1 differentiation 85:99 mouse ESC differentiation 75:99 mouse ESC differentiation 75:99 Elevated O-GlcNAc levels activate epigenetically repressed genes and delay mouse ESC differentiation without affecting naïve to primed cell transition. 24898611 3 5 theme O-GlcNAcylation 683:697 arg1 levels 665:670 increased levels 655:670 increased levels of protein O-GlcNAcylation 655:697 Here, we demonstrate that the specific inhibition of O-GlcNAc hydrolase (Oga) causes increased levels of protein O-GlcNAcylation and impairs differentiation of mouse ESCs both in serum-free monolayer and in embryoid bodies (EBs). 24898611 6 6 theme Dppa3 1235:1239 arg1 downregulation 1241:1254 Dppa3 downregulation 1235:1254 Dppa3 downregulation 1235:1254 However, the transition of naïve cells to primed pluripotency indicated by Rex1 (Zfp42), Nanog, Esrrb, and Dppa3 downregulation and Fgf5 upregulation remains unchanged. 24898611 1 7 theme mouse 175:179 arg1 cells 196:200 mouse embryonic stem cells 175:200 mouse embryonic stem cells (ESCs) 175:207 The differentiation of mouse embryonic stem cells (ESCs) is controlled by the interaction of multiple signaling pathways, typically mediated by post-translational protein modifications. 24898611 1 7 theme mouse 175:179 arg1 ESCs 203:206 ESCs 203:206 ESCs 203:206 The differentiation of mouse embryonic stem cells (ESCs) is controlled by the interaction of multiple signaling pathways, typically mediated by post-translational protein modifications. 24898611 1 8 theme signaling 254:262 arg1 pathways 264:271 multiple signaling pathways 245:271 multiple signaling pathways 245:271 The differentiation of mouse embryonic stem cells (ESCs) is controlled by the interaction of multiple signaling pathways, typically mediated by post-translational protein modifications. 24898611 4 9 theme Sox1-expressing 898:912 arg1 progenitors 921:931 Sox1-expressing neural progenitors 898:931 Sox1-expressing neural progenitors generated following induction of neural differentiation as well as maintained expression of the ESC marker Oct4 (Pou5f1) 898:1052 Use of reporter cell lines demonstrates that Oga inhibition leads to a reduction in the number of Sox1-expressing neural progenitors generated following induction of neural differentiation as well as maintained expression of the ESC marker Oct4 (Pou5f1). 24898611 2 10 link O-linked 354:361 arg1 O-GlcNAc 384:391 O-GlcNAc 384:391 O-GlcNAc 384:391 The addition of O-linked N-acetylglucosamine (O-GlcNAc) to serine and threonine residues of nuclear and cytoplasmic proteins is one such modification (O-GlcNAcylation), whose function in ESCs is only now beginning to be elucidated. 24898611 2 10 link O-linked 354:361 arg1 N-acetylglucosamine 363:381 O-linked N-acetylglucosamine 354:381 O-linked N-acetylglucosamine (O-GlcNAc) 354:392 The addition of O-linked N-acetylglucosamine (O-GlcNAc) to serine and threonine residues of nuclear and cytoplasmic proteins is one such modification (O-GlcNAcylation), whose function in ESCs is only now beginning to be elucidated. 24898611 1 11 theme pathways 264:271 arg1 interaction 230:240 the interaction 226:240 the interaction 226:240 The differentiation of mouse embryonic stem cells (ESCs) is controlled by the interaction of multiple signaling pathways, typically mediated by post-translational protein modifications. 24898611 3 12 theme ESCs 736:739 arg1 differentiation 711:725 differentiation 711:725 differentiation of mouse ESCs both in serum-free monolayer and in embryoid bodies (EBs) 711:797 Here, we demonstrate that the specific inhibition of O-GlcNAc hydrolase (Oga) causes increased levels of protein O-GlcNAcylation and impairs differentiation of mouse ESCs both in serum-free monolayer and in embryoid bodies (EBs). 24898611 4 13 theme marker 1033:1038 arg1 Pou5f1 1046:1051 Pou5f1 1046:1051 Pou5f1 1046:1051 Use of reporter cell lines demonstrates that Oga inhibition leads to a reduction in the number of Sox1-expressing neural progenitors generated following induction of neural differentiation as well as maintained expression of the ESC marker Oct4 (Pou5f1). 24898611 4 13 theme marker 1033:1038 arg1 Oct4 1040:1043 the ESC marker Oct4 1025:1043 the ESC marker Oct4 (Pou5f1) 1025:1052 Use of reporter cell lines demonstrates that Oga inhibition leads to a reduction in the number of Sox1-expressing neural progenitors generated following induction of neural differentiation as well as maintained expression of the ESC marker Oct4 (Pou5f1). 24898611 6 14 theme cells 1161:1165 arg1 transition 1141:1150 the transition 1137:1150 the transition of naïve cells to primed pluripotency indicated by Rex1 (Zfp42), Nanog, Esrrb, and Dppa3 downregulation and Fgf5 upregulation 1137:1276 However, the transition of naïve cells to primed pluripotency indicated by Rex1 (Zfp42), Nanog, Esrrb, and Dppa3 downregulation and Fgf5 upregulation remains unchanged. 24898611 4 15 theme neural 966:971 arg1 differentiation 973:987 neural differentiation 966:987 neural differentiation 966:987 Use of reporter cell lines demonstrates that Oga inhibition leads to a reduction in the number of Sox1-expressing neural progenitors generated following induction of neural differentiation as well as maintained expression of the ESC marker Oct4 (Pou5f1). 24898611 6 16 theme naïve 1155:1159 arg1 cells 1161:1165 naïve cells 1155:1165 naïve cells 1155:1165 However, the transition of naïve cells to primed pluripotency indicated by Rex1 (Zfp42), Nanog, Esrrb, and Dppa3 downregulation and Fgf5 upregulation remains unchanged. 24898611 1 17 theme embryonic 181:189 arg1 cells 196:200 mouse embryonic stem cells 175:200 mouse embryonic stem cells (ESCs) 175:207 The differentiation of mouse embryonic stem cells (ESCs) is controlled by the interaction of multiple signaling pathways, typically mediated by post-translational protein modifications. 24898611 1 17 theme embryonic 181:189 arg1 ESCs 203:206 ESCs 203:206 ESCs 203:206 The differentiation of mouse embryonic stem cells (ESCs) is controlled by the interaction of multiple signaling pathways, typically mediated by post-translational protein modifications. 24898611 5 18 theme endodermal 1092:1101 arg1 markers 1103:1109 mesodermal and endodermal markers 1077:1109 mesodermal and endodermal markers 1077:1109 In EBs, expression of mesodermal and endodermal markers is also delayed. 24898611 4 19 theme ESC 1029:1031 arg1 Pou5f1 1046:1051 Pou5f1 1046:1051 Pou5f1 1046:1051 Use of reporter cell lines demonstrates that Oga inhibition leads to a reduction in the number of Sox1-expressing neural progenitors generated following induction of neural differentiation as well as maintained expression of the ESC marker Oct4 (Pou5f1). 24898611 4 19 theme ESC 1029:1031 arg1 Oct4 1040:1043 the ESC marker Oct4 1025:1043 the ESC marker Oct4 (Pou5f1) 1025:1052 Use of reporter cell lines demonstrates that Oga inhibition leads to a reduction in the number of Sox1-expressing neural progenitors generated following induction of neural differentiation as well as maintained expression of the ESC marker Oct4 (Pou5f1). 24898611 1 20 theme stem 191:194 arg1 cells 196:200 mouse embryonic stem cells 175:200 mouse embryonic stem cells (ESCs) 175:207 The differentiation of mouse embryonic stem cells (ESCs) is controlled by the interaction of multiple signaling pathways, typically mediated by post-translational protein modifications. 24898611 1 20 theme stem 191:194 arg1 ESCs 203:206 ESCs 203:206 ESCs 203:206 The differentiation of mouse embryonic stem cells (ESCs) is controlled by the interaction of multiple signaling pathways, typically mediated by post-translational protein modifications. 24898611 0 21 theme O-GlcNAc 9:16 arg1 levels 18:23 Elevated O-GlcNAc levels 0:23 Elevated O-GlcNAc levels 0:23 Elevated O-GlcNAc levels activate epigenetically repressed genes and delay mouse ESC differentiation without affecting naïve to primed cell transition. 24898611 3 22 theme mouse 730:734 arg1 ESCs 736:739 mouse ESCs 730:739 mouse ESCs 730:739 Here, we demonstrate that the specific inhibition of O-GlcNAc hydrolase (Oga) causes increased levels of protein O-GlcNAcylation and impairs differentiation of mouse ESCs both in serum-free monolayer and in embryoid bodies (EBs). 24898611 7 23 theme protein 1465:1471 arg1 modification 1473:1484 this protein modification 1460:1484 this protein modification 1460:1484 Finally, we demonstrate that increased O-GlcNAcylation results in upregulation of genes normally epigenetically silenced in ESCs, supporting the emerging role for this protein modification in the regulation of histone modifications and DNA methylation. 24898611 1 24 theme cells 196:200 arg1 differentiation 156:170 The differentiation 152:170 The differentiation of mouse embryonic stem cells (ESCs) 152:207 The differentiation of mouse embryonic stem cells (ESCs) is controlled by the interaction of multiple signaling pathways, typically mediated by post-translational protein modifications. 24898611 0 25 theme Elevated 0:7 arg1 levels 18:23 Elevated O-GlcNAc levels 0:23 Elevated O-GlcNAc levels 0:23 Elevated O-GlcNAc levels activate epigenetically repressed genes and delay mouse ESC differentiation without affecting naïve to primed cell transition. 24898611 4 26 theme Oga 845:847 arg1 inhibition 849:858 Oga inhibition 845:858 Oga inhibition 845:858 Use of reporter cell lines demonstrates that Oga inhibition leads to a reduction in the number of Sox1-expressing neural progenitors generated following induction of neural differentiation as well as maintained expression of the ESC marker Oct4 (Pou5f1). 24898611 0 27 theme cell 135:138 arg1 transition 140:149 primed cell transition 128:149 primed cell transition 128:149 Elevated O-GlcNAc levels activate epigenetically repressed genes and delay mouse ESC differentiation without affecting naïve to primed cell transition. 24898611 2 28 theme cytoplasmic 442:452 arg1 proteins 454:461 nuclear and cytoplasmic proteins 430:461 nuclear and cytoplasmic proteins 430:461 The addition of O-linked N-acetylglucosamine (O-GlcNAc) to serine and threonine residues of nuclear and cytoplasmic proteins is one such modification (O-GlcNAcylation), whose function in ESCs is only now beginning to be elucidated. 24898611 2 29 theme proteins 454:461 arg1 threonine 408:416 threonine 408:416 threonine 408:416 The addition of O-linked N-acetylglucosamine (O-GlcNAc) to serine and threonine residues of nuclear and cytoplasmic proteins is one such modification (O-GlcNAcylation), whose function in ESCs is only now beginning to be elucidated. 24898611 2 29 theme proteins 454:461 arg1 serine 397:402 serine 397:402 serine 397:402 The addition of O-linked N-acetylglucosamine (O-GlcNAc) to serine and threonine residues of nuclear and cytoplasmic proteins is one such modification (O-GlcNAcylation), whose function in ESCs is only now beginning to be elucidated. 24898611 0 30 theme primed 128:133 arg1 transition 140:149 primed cell transition 128:149 primed cell transition 128:149 Elevated O-GlcNAc levels activate epigenetically repressed genes and delay mouse ESC differentiation without affecting naïve to primed cell transition. 24898611 4 31 theme progenitors 921:931 arg1 number 888:893 the number 884:893 the number of Sox1-expressing neural progenitors generated following induction of neural differentiation as well as maintained expression of the ESC marker Oct4 (Pou5f1) 884:1052 Use of reporter cell lines demonstrates that Oga inhibition leads to a reduction in the number of Sox1-expressing neural progenitors generated following induction of neural differentiation as well as maintained expression of the ESC marker Oct4 (Pou5f1). 24898611 7 32 theme genes 1379:1383 arg1 upregulation 1363:1374 upregulation 1363:1374 upregulation of genes normally epigenetically silenced in ESCs 1363:1424 Finally, we demonstrate that increased O-GlcNAcylation results in upregulation of genes normally epigenetically silenced in ESCs, supporting the emerging role for this protein modification in the regulation of histone modifications and DNA methylation. 24898611 7 33 from role 1451:1454 arg1 regulation 1493:1502 the regulation 1489:1502 the regulation of histone modifications and DNA methylation 1489:1547 Finally, we demonstrate that increased O-GlcNAcylation results in upregulation of genes normally epigenetically silenced in ESCs, supporting the emerging role for this protein modification in the regulation of histone modifications and DNA methylation. 24898611 7 34 theme increased 1326:1334 arg1 O-GlcNAcylation 1336:1350 increased O-GlcNAcylation 1326:1350 increased O-GlcNAcylation 1326:1350 Finally, we demonstrate that increased O-GlcNAcylation results in upregulation of genes normally epigenetically silenced in ESCs, supporting the emerging role for this protein modification in the regulation of histone modifications and DNA methylation. 24898611 0 35 theme repressed 49:57 arg1 genes 59:63 epigenetically repressed genes 34:63 epigenetically repressed genes 34:63 Elevated O-GlcNAc levels activate epigenetically repressed genes and delay mouse ESC differentiation without affecting naïve to primed cell transition. 24898611 1 36 theme post-translational 296:313 arg1 modifications 323:335 post-translational protein modifications 296:335 post-translational protein modifications 296:335 The differentiation of mouse embryonic stem cells (ESCs) is controlled by the interaction of multiple signaling pathways, typically mediated by post-translational protein modifications. 24898611 7 37 theme DNA 1533:1535 arg1 methylation 1537:1547 DNA methylation 1533:1547 DNA methylation 1533:1547 Finally, we demonstrate that increased O-GlcNAcylation results in upregulation of genes normally epigenetically silenced in ESCs, supporting the emerging role for this protein modification in the regulation of histone modifications and DNA methylation. 24898611 4 38 theme reporter 807:814 arg1 lines 821:825 reporter cell lines 807:825 reporter cell lines 807:825 Use of reporter cell lines demonstrates that Oga inhibition leads to a reduction in the number of Sox1-expressing neural progenitors generated following induction of neural differentiation as well as maintained expression of the ESC marker Oct4 (Pou5f1). 24898611 6 39 theme primed 1170:1175 arg1 pluripotency 1177:1188 primed pluripotency 1170:1188 primed pluripotency indicated by Rex1 (Zfp42), Nanog, Esrrb, and Dppa3 downregulation and Fgf5 upregulation 1170:1276 However, the transition of naïve cells to primed pluripotency indicated by Rex1 (Zfp42), Nanog, Esrrb, and Dppa3 downregulation and Fgf5 upregulation remains unchanged. 24898611 2 40 theme nuclear 430:436 arg1 proteins 454:461 nuclear and cytoplasmic proteins 430:461 nuclear and cytoplasmic proteins 430:461 The addition of O-linked N-acetylglucosamine (O-GlcNAc) to serine and threonine residues of nuclear and cytoplasmic proteins is one such modification (O-GlcNAcylation), whose function in ESCs is only now beginning to be elucidated. 24898611 4 41 theme maintained 1000:1009 arg1 expression 1011:1020 maintained expression 1000:1020 induction of neural differentiation as well as maintained expression of the ESC marker Oct4 (Pou5f1) 953:1052 Use of reporter cell lines demonstrates that Oga inhibition leads to a reduction in the number of Sox1-expressing neural progenitors generated following induction of neural differentiation as well as maintained expression of the ESC marker Oct4 (Pou5f1). 24898611 1 42 theme protein 315:321 arg1 modifications 323:335 post-translational protein modifications 296:335 post-translational protein modifications 296:335 The differentiation of mouse embryonic stem cells (ESCs) is controlled by the interaction of multiple signaling pathways, typically mediated by post-translational protein modifications. 24898611 3 43 theme hydrolase 632:640 arg1 inhibition 609:618 the specific inhibition 596:618 the specific inhibition of O-GlcNAc hydrolase (Oga) 596:646 Here, we demonstrate that the specific inhibition of O-GlcNAc hydrolase (Oga) causes increased levels of protein O-GlcNAcylation and impairs differentiation of mouse ESCs both in serum-free monolayer and in embryoid bodies (EBs). 24898611 7 44 theme histone 1507:1513 arg1 modifications 1515:1527 histone modifications 1507:1527 histone modifications 1507:1527 Finally, we demonstrate that increased O-GlcNAcylation results in upregulation of genes normally epigenetically silenced in ESCs, supporting the emerging role for this protein modification in the regulation of histone modifications and DNA methylation. 24898611 3 45 theme specific 600:607 arg1 inhibition 609:618 the specific inhibition 596:618 the specific inhibition of O-GlcNAc hydrolase (Oga) 596:646 Here, we demonstrate that the specific inhibition of O-GlcNAc hydrolase (Oga) causes increased levels of protein O-GlcNAcylation and impairs differentiation of mouse ESCs both in serum-free monolayer and in embryoid bodies (EBs). 24898611 7 46 theme modifications 1515:1527 arg1 regulation 1493:1502 the regulation 1489:1502 the regulation of histone modifications and DNA methylation 1489:1547 Finally, we demonstrate that increased O-GlcNAcylation results in upregulation of genes normally epigenetically silenced in ESCs, supporting the emerging role for this protein modification in the regulation of histone modifications and DNA methylation. 24898611 7 47 theme emerging 1442:1449 arg1 role 1451:1454 the emerging role 1438:1454 the emerging role for this protein modification in the regulation of histone modifications and DNA methylation 1438:1547 Finally, we demonstrate that increased O-GlcNAcylation results in upregulation of genes normally epigenetically silenced in ESCs, supporting the emerging role for this protein modification in the regulation of histone modifications and DNA methylation. 24898611 2 48 from function 513:520 arg1 ESCs 525:528 ESCs 525:528 ESCs 525:528 The addition of O-linked N-acetylglucosamine (O-GlcNAc) to serine and threonine residues of nuclear and cytoplasmic proteins is one such modification (O-GlcNAcylation), whose function in ESCs is only now beginning to be elucidated. 24898611 4 49 theme lines 821:825 arg1 Use 800:802 Use 800:802 Use of reporter cell lines 800:825 Use of reporter cell lines demonstrates that Oga inhibition leads to a reduction in the number of Sox1-expressing neural progenitors generated following induction of neural differentiation as well as maintained expression of the ESC marker Oct4 (Pou5f1). 24898611 2 50 theme N-acetylglucosamine 363:381 arg1 addition 342:349 The addition 338:349 The addition of O-linked N-acetylglucosamine (O-GlcNAc) to serine and threonine residues of nuclear and cytoplasmic proteins 338:461 The addition of O-linked N-acetylglucosamine (O-GlcNAc) to serine and threonine residues of nuclear and cytoplasmic proteins is one such modification (O-GlcNAcylation), whose function in ESCs is only now beginning to be elucidated. 24898611 2 50 theme N-acetylglucosamine 363:381 arg1 modification 475:486 one such modification 466:486 one such modification (O-GlcNAcylation) 466:504 The addition of O-linked N-acetylglucosamine (O-GlcNAc) to serine and threonine residues of nuclear and cytoplasmic proteins is one such modification (O-GlcNAcylation), whose function in ESCs is only now beginning to be elucidated. 24898611 3 51 from differentiation 711:725 arg1 monolayer 760:768 serum-free monolayer 749:768 serum-free monolayer 749:768 Here, we demonstrate that the specific inhibition of O-GlcNAc hydrolase (Oga) causes increased levels of protein O-GlcNAcylation and impairs differentiation of mouse ESCs both in serum-free monolayer and in embryoid bodies (EBs). 24898611 3 51 from differentiation 711:725 arg1 EBs 794:796 EBs 794:796 EBs 794:796 Here, we demonstrate that the specific inhibition of O-GlcNAc hydrolase (Oga) causes increased levels of protein O-GlcNAcylation and impairs differentiation of mouse ESCs both in serum-free monolayer and in embryoid bodies (EBs). 24898611 3 51 from differentiation 711:725 arg1 bodies 786:791 embryoid bodies 777:791 embryoid bodies (EBs) 777:797 Here, we demonstrate that the specific inhibition of O-GlcNAc hydrolase (Oga) causes increased levels of protein O-GlcNAcylation and impairs differentiation of mouse ESCs both in serum-free monolayer and in embryoid bodies (EBs). 24898611 4 52 theme neural 914:919 arg1 progenitors 921:931 Sox1-expressing neural progenitors 898:931 Sox1-expressing neural progenitors generated following induction of neural differentiation as well as maintained expression of the ESC marker Oct4 (Pou5f1) 898:1052 Use of reporter cell lines demonstrates that Oga inhibition leads to a reduction in the number of Sox1-expressing neural progenitors generated following induction of neural differentiation as well as maintained expression of the ESC marker Oct4 (Pou5f1). 24898611 4 53 theme cell 816:819 arg1 lines 821:825 reporter cell lines 807:825 reporter cell lines 807:825 Use of reporter cell lines demonstrates that Oga inhibition leads to a reduction in the number of Sox1-expressing neural progenitors generated following induction of neural differentiation as well as maintained expression of the ESC marker Oct4 (Pou5f1). 24898611 2 54 theme O-linked 354:361 arg1 O-GlcNAc 384:391 O-GlcNAc 384:391 O-GlcNAc 384:391 The addition of O-linked N-acetylglucosamine (O-GlcNAc) to serine and threonine residues of nuclear and cytoplasmic proteins is one such modification (O-GlcNAcylation), whose function in ESCs is only now beginning to be elucidated. 24898611 2 54 theme O-linked 354:361 arg1 N-acetylglucosamine 363:381 O-linked N-acetylglucosamine 354:381 O-linked N-acetylglucosamine (O-GlcNAc) 354:392 The addition of O-linked N-acetylglucosamine (O-GlcNAc) to serine and threonine residues of nuclear and cytoplasmic proteins is one such modification (O-GlcNAcylation), whose function in ESCs is only now beginning to be elucidated. 24898611 3 55 theme embryoid 777:784 arg1 EBs 794:796 EBs 794:796 EBs 794:796 Here, we demonstrate that the specific inhibition of O-GlcNAc hydrolase (Oga) causes increased levels of protein O-GlcNAcylation and impairs differentiation of mouse ESCs both in serum-free monolayer and in embryoid bodies (EBs). 24898611 3 55 theme embryoid 777:784 arg1 bodies 786:791 embryoid bodies 777:791 embryoid bodies (EBs) 777:797 Here, we demonstrate that the specific inhibition of O-GlcNAc hydrolase (Oga) causes increased levels of protein O-GlcNAcylation and impairs differentiation of mouse ESCs both in serum-free monolayer and in embryoid bodies (EBs). 24898611 6 56 theme Fgf5 1260:1263 arg1 upregulation 1265:1276 Fgf5 upregulation 1260:1276 Fgf5 upregulation 1260:1276 However, the transition of naïve cells to primed pluripotency indicated by Rex1 (Zfp42), Nanog, Esrrb, and Dppa3 downregulation and Fgf5 upregulation remains unchanged. 24898611 3 57 theme protein 675:681 arg1 O-GlcNAcylation 683:697 protein O-GlcNAcylation 675:697 protein O-GlcNAcylation 675:697 Here, we demonstrate that the specific inhibition of O-GlcNAc hydrolase (Oga) causes increased levels of protein O-GlcNAcylation and impairs differentiation of mouse ESCs both in serum-free monolayer and in embryoid bodies (EBs). 24898611 3 58 theme O-GlcNAc 623:630 arg1 Oga 643:645 Oga 643:645 Oga 643:645 Here, we demonstrate that the specific inhibition of O-GlcNAc hydrolase (Oga) causes increased levels of protein O-GlcNAcylation and impairs differentiation of mouse ESCs both in serum-free monolayer and in embryoid bodies (EBs). 24898611 3 58 theme O-GlcNAc 623:630 arg1 hydrolase 632:640 O-GlcNAc hydrolase 623:640 O-GlcNAc hydrolase (Oga) 623:646 Here, we demonstrate that the specific inhibition of O-GlcNAc hydrolase (Oga) causes increased levels of protein O-GlcNAcylation and impairs differentiation of mouse ESCs both in serum-free monolayer and in embryoid bodies (EBs). 24898611 3 59 theme increased 655:663 arg1 levels 665:670 increased levels 655:670 increased levels of protein O-GlcNAcylation 655:697 Here, we demonstrate that the specific inhibition of O-GlcNAc hydrolase (Oga) causes increased levels of protein O-GlcNAcylation and impairs differentiation of mouse ESCs both in serum-free monolayer and in embryoid bodies (EBs). 24898611 2 60 dep serine 397:402 arg1 residues 418:425 residues 418:425 residues 418:425 The addition of O-linked N-acetylglucosamine (O-GlcNAc) to serine and threonine residues of nuclear and cytoplasmic proteins is one such modification (O-GlcNAcylation), whose function in ESCs is only now beginning to be elucidated. 24898611 7 61 theme methylation 1537:1547 arg1 regulation 1493:1502 the regulation 1489:1502 the regulation of histone modifications and DNA methylation 1489:1547 Finally, we demonstrate that increased O-GlcNAcylation results in upregulation of genes normally epigenetically silenced in ESCs, supporting the emerging role for this protein modification in the regulation of histone modifications and DNA methylation. 24898611 0 62 theme mouse 75:79 arg1 differentiation 85:99 mouse ESC differentiation 75:99 mouse ESC differentiation 75:99 Elevated O-GlcNAc levels activate epigenetically repressed genes and delay mouse ESC differentiation without affecting naïve to primed cell transition. 24898611 4 63 theme differentiation 973:987 arg1 induction 953:961 induction 953:961 induction of neural differentiation as well as maintained expression of the ESC marker Oct4 (Pou5f1) 953:1052 Use of reporter cell lines demonstrates that Oga inhibition leads to a reduction in the number of Sox1-expressing neural progenitors generated following induction of neural differentiation as well as maintained expression of the ESC marker Oct4 (Pou5f1). 24898611 4 63 theme differentiation 973:987 arg1 expression 1011:1020 maintained expression 1000:1020 induction of neural differentiation as well as maintained expression of the ESC marker Oct4 (Pou5f1) 953:1052 Use of reporter cell lines demonstrates that Oga inhibition leads to a reduction in the number of Sox1-expressing neural progenitors generated following induction of neural differentiation as well as maintained expression of the ESC marker Oct4 (Pou5f1). 24898611 4 64 from reduction 871:879 arg1 number 888:893 the number 884:893 the number of Sox1-expressing neural progenitors generated following induction of neural differentiation as well as maintained expression of the ESC marker Oct4 (Pou5f1) 884:1052 Use of reporter cell lines demonstrates that Oga inhibition leads to a reduction in the number of Sox1-expressing neural progenitors generated following induction of neural differentiation as well as maintained expression of the ESC marker Oct4 (Pou5f1). 24898611 4 65 theme Oct4 1040:1043 arg1 induction 953:961 induction 953:961 induction of neural differentiation as well as maintained expression of the ESC marker Oct4 (Pou5f1) 953:1052 Use of reporter cell lines demonstrates that Oga inhibition leads to a reduction in the number of Sox1-expressing neural progenitors generated following induction of neural differentiation as well as maintained expression of the ESC marker Oct4 (Pou5f1). 24898611 4 65 theme Oct4 1040:1043 arg1 expression 1011:1020 maintained expression 1000:1020 induction of neural differentiation as well as maintained expression of the ESC marker Oct4 (Pou5f1) 953:1052 Use of reporter cell lines demonstrates that Oga inhibition leads to a reduction in the number of Sox1-expressing neural progenitors generated following induction of neural differentiation as well as maintained expression of the ESC marker Oct4 (Pou5f1). 24898611 2 66 theme such 470:473 arg1 addition 342:349 The addition 338:349 The addition of O-linked N-acetylglucosamine (O-GlcNAc) to serine and threonine residues of nuclear and cytoplasmic proteins 338:461 The addition of O-linked N-acetylglucosamine (O-GlcNAc) to serine and threonine residues of nuclear and cytoplasmic proteins is one such modification (O-GlcNAcylation), whose function in ESCs is only now beginning to be elucidated. 24898611 2 66 theme such 470:473 arg1 O-GlcNAcylation 489:503 O-GlcNAcylation 489:503 O-GlcNAcylation 489:503 The addition of O-linked N-acetylglucosamine (O-GlcNAc) to serine and threonine residues of nuclear and cytoplasmic proteins is one such modification (O-GlcNAcylation), whose function in ESCs is only now beginning to be elucidated. 24898611 2 66 theme such 470:473 arg1 modification 475:486 one such modification 466:486 one such modification (O-GlcNAcylation) 466:504 The addition of O-linked N-acetylglucosamine (O-GlcNAc) to serine and threonine residues of nuclear and cytoplasmic proteins is one such modification (O-GlcNAcylation), whose function in ESCs is only now beginning to be elucidated. 24144119 0 0 theme O-GlcNAc-modified 87:103 arg1 proteins 105:112 O-GlcNAc-modified proteins 87:112 O-GlcNAc-modified proteins 87:112 Multiple reaction monitoring mass spectrometry for the discovery and quantification of O-GlcNAc-modified proteins. 24144119 3 1 theme MS 517:518 arg1 method 520:525 a targeted MS method 506:525 a targeted MS method 506:525 Here, we investigate the potential of Multiple Reaction Monitoring Mass Spectrometry (MRM-MS), a targeted MS method, to detect and quantify native O-GlcNAc modified peptides without extensive labeling and enrichment. 24144119 3 1 theme MS 517:518 arg1 Spectrometry 483:494 Multiple Reaction Monitoring Mass Spectrometry 449:494 Multiple Reaction Monitoring Mass Spectrometry (MRM-MS) 449:503 Here, we investigate the potential of Multiple Reaction Monitoring Mass Spectrometry (MRM-MS), a targeted MS method, to detect and quantify native O-GlcNAc modified peptides without extensive labeling and enrichment. 24144119 7 2 theme human 1186:1190 arg1 hESC 1214:1217 hESC 1214:1217 hESC 1214:1217 We demonstrate that GSK-3β is itself modified by O-GlcNAc in human embryonic stem cells (hESC). 24144119 7 2 theme human 1186:1190 arg1 cells 1207:1211 human embryonic stem cells 1186:1211 human embryonic stem cells (hESC) 1186:1218 We demonstrate that GSK-3β is itself modified by O-GlcNAc in human embryonic stem cells (hESC). 24144119 5 3 theme whole 889:893 arg1 lysate 900:905 a trypsin-digested whole cell lysate 870:905 a trypsin-digested whole cell lysate 870:905 In addition, when diluted by 100-fold in a trypsin-digested whole cell lysate, the O-GlcNAcylated peptide remains detectable. 24144119 5 4 theme cell 895:898 arg1 lysate 900:905 a trypsin-digested whole cell lysate 870:905 a trypsin-digested whole cell lysate 870:905 In addition, when diluted by 100-fold in a trypsin-digested whole cell lysate, the O-GlcNAcylated peptide remains detectable. 24144119 11 5 theme modified 1737:1744 arg1 peptides 1746:1753 native O-GlcNAc modified peptides 1721:1753 native O-GlcNAc modified peptides 1721:1753 To the best of our knowledge, this is the first report utilizing MRM-MS to detect native O-GlcNAc modified peptides. 24144119 10 6 gly O-GlcNAcylation 1561:1575 arg1 mechanism 1628:1636 an autoinhibition mechanism 1610:1636 an autoinhibition mechanism 1610:1636 This novel O-GlcNAcylation could potentially be involved in an autoinhibition mechanism. 24144119 8 7 theme O-GlcNAcylated 1342:1355 arg1 peptide 1364:1370 a novel O-GlcNAcylated GSK-3β peptide 1334:1370 a novel O-GlcNAcylated GSK-3β peptide 1334:1370 Indeed, by only using gel electrophoresis to grossly enrich GSK-3β from whole cell lysate, we discover by MRM-MS a novel O-GlcNAcylated GSK-3β peptide, bearing 3 potential O-GlcNAcylation sites. 24144119 4 8 theme O-GlcNAcylated 765:778 arg1 peptide 780:786 O-GlcNAcylated peptide 765:786 O-GlcNAcylated peptide 765:786 We report the ability of MRM-MS to detect a standard O-GlcNAcylated peptide and show that the method is robust to quantify the amount of O-GlcNAcylated peptide with a method detection limit of 3 fmol. 24144119 0 9 theme proteins 105:112 arg1 quantification 69:82 quantification 69:82 quantification 69:82 Multiple reaction monitoring mass spectrometry for the discovery and quantification of O-GlcNAc-modified proteins. 24144119 0 9 theme proteins 105:112 arg1 discovery 55:63 discovery 55:63 discovery 55:63 Multiple reaction monitoring mass spectrometry for the discovery and quantification of O-GlcNAc-modified proteins. 24144119 9 10 theme hESC 1497:1500 arg1 treatment 1502:1510 hESC treatment 1497:1510 hESC treatment with an O-GlcNAc hydrolase inhibitor 1497:1547 We confirm our finding by quantifying the increase of O-GlcNAcylation, following hESC treatment with an O-GlcNAc hydrolase inhibitor. 24144119 3 11 theme native 551:556 arg1 peptides 576:583 native O-GlcNAc modified peptides 551:583 native O-GlcNAc modified peptides 551:583 Here, we investigate the potential of Multiple Reaction Monitoring Mass Spectrometry (MRM-MS), a targeted MS method, to detect and quantify native O-GlcNAc modified peptides without extensive labeling and enrichment. 24144119 8 12 theme gel 1243:1245 arg1 electrophoresis 1247:1261 gel electrophoresis 1243:1261 gel electrophoresis 1243:1261 Indeed, by only using gel electrophoresis to grossly enrich GSK-3β from whole cell lysate, we discover by MRM-MS a novel O-GlcNAcylated GSK-3β peptide, bearing 3 potential O-GlcNAcylation sites. 24144119 10 13 theme autoinhibition 1613:1626 arg1 mechanism 1628:1636 an autoinhibition mechanism 1610:1636 an autoinhibition mechanism 1610:1636 This novel O-GlcNAcylation could potentially be involved in an autoinhibition mechanism. 24144119 3 14 theme Reaction 458:465 arg1 Spectrometry 483:494 Multiple Reaction Monitoring Mass Spectrometry 449:494 Multiple Reaction Monitoring Mass Spectrometry (MRM-MS) 449:503 Here, we investigate the potential of Multiple Reaction Monitoring Mass Spectrometry (MRM-MS), a targeted MS method, to detect and quantify native O-GlcNAc modified peptides without extensive labeling and enrichment. 24144119 3 14 theme Reaction 458:465 arg1 MRM-MS 497:502 MRM-MS 497:502 MRM-MS 497:502 Here, we investigate the potential of Multiple Reaction Monitoring Mass Spectrometry (MRM-MS), a targeted MS method, to detect and quantify native O-GlcNAc modified peptides without extensive labeling and enrichment. 24144119 3 14 theme Reaction 458:465 arg1 method 520:525 a targeted MS method 506:525 a targeted MS method 506:525 Here, we investigate the potential of Multiple Reaction Monitoring Mass Spectrometry (MRM-MS), a targeted MS method, to detect and quantify native O-GlcNAc modified peptides without extensive labeling and enrichment. 24144119 11 15 theme native 1721:1726 arg1 peptides 1746:1753 native O-GlcNAc modified peptides 1721:1753 native O-GlcNAc modified peptides 1721:1753 To the best of our knowledge, this is the first report utilizing MRM-MS to detect native O-GlcNAc modified peptides. 24144119 4 16 theme peptide 780:786 arg1 amount 755:760 the amount 751:760 the amount of O-GlcNAcylated peptide 751:786 We report the ability of MRM-MS to detect a standard O-GlcNAcylated peptide and show that the method is robust to quantify the amount of O-GlcNAcylated peptide with a method detection limit of 3 fmol. 24144119 4 16 theme peptide 780:786 arg1 peptide 780:786 O-GlcNAcylated peptide 765:786 O-GlcNAcylated peptide 765:786 We report the ability of MRM-MS to detect a standard O-GlcNAcylated peptide and show that the method is robust to quantify the amount of O-GlcNAcylated peptide with a method detection limit of 3 fmol. 24144119 3 17 theme Monitoring 467:476 arg1 Spectrometry 483:494 Multiple Reaction Monitoring Mass Spectrometry 449:494 Multiple Reaction Monitoring Mass Spectrometry (MRM-MS) 449:503 Here, we investigate the potential of Multiple Reaction Monitoring Mass Spectrometry (MRM-MS), a targeted MS method, to detect and quantify native O-GlcNAc modified peptides without extensive labeling and enrichment. 24144119 3 17 theme Monitoring 467:476 arg1 MRM-MS 497:502 MRM-MS 497:502 MRM-MS 497:502 Here, we investigate the potential of Multiple Reaction Monitoring Mass Spectrometry (MRM-MS), a targeted MS method, to detect and quantify native O-GlcNAc modified peptides without extensive labeling and enrichment. 24144119 3 17 theme Monitoring 467:476 arg1 method 520:525 a targeted MS method 506:525 a targeted MS method 506:525 Here, we investigate the potential of Multiple Reaction Monitoring Mass Spectrometry (MRM-MS), a targeted MS method, to detect and quantify native O-GlcNAc modified peptides without extensive labeling and enrichment. 24144119 9 18 theme O-GlcNAcylation 1470:1484 arg1 increase 1458:1465 the increase 1454:1465 the increase of O-GlcNAcylation 1454:1484 We confirm our finding by quantifying the increase of O-GlcNAcylation, following hESC treatment with an O-GlcNAc hydrolase inhibitor. 24144119 4 19 theme MRM-MS 653:658 arg1 ability 642:648 the ability 638:648 the ability of MRM-MS to detect a standard O-GlcNAcylated peptide 638:702 We report the ability of MRM-MS to detect a standard O-GlcNAcylated peptide and show that the method is robust to quantify the amount of O-GlcNAcylated peptide with a method detection limit of 3 fmol. 24144119 10 20 theme novel 1555:1559 arg1 O-GlcNAcylation 1561:1575 This novel O-GlcNAcylation 1550:1575 This novel O-GlcNAcylation 1550:1575 This novel O-GlcNAcylation could potentially be involved in an autoinhibition mechanism. 24144119 7 21 theme embryonic 1192:1200 arg1 hESC 1214:1217 hESC 1214:1217 hESC 1214:1217 We demonstrate that GSK-3β is itself modified by O-GlcNAc in human embryonic stem cells (hESC). 24144119 7 21 theme embryonic 1192:1200 arg1 cells 1207:1211 human embryonic stem cells 1186:1211 human embryonic stem cells (hESC) 1186:1218 We demonstrate that GSK-3β is itself modified by O-GlcNAc in human embryonic stem cells (hESC). 24144119 4 22 theme O-GlcNAcylated 681:694 arg1 peptide 696:702 a standard O-GlcNAcylated peptide 670:702 a standard O-GlcNAcylated peptide 670:702 We report the ability of MRM-MS to detect a standard O-GlcNAcylated peptide and show that the method is robust to quantify the amount of O-GlcNAcylated peptide with a method detection limit of 3 fmol. 24144119 0 23 theme Multiple 0:7 arg1 reaction 9:16 Multiple reaction 0:16 Multiple reaction 0:16 Multiple reaction monitoring mass spectrometry for the discovery and quantification of O-GlcNAc-modified proteins. 24144119 9 24 theme hydrolase 1529:1537 arg1 inhibitor 1539:1547 an O-GlcNAc hydrolase inhibitor 1517:1547 an O-GlcNAc hydrolase inhibitor 1517:1547 We confirm our finding by quantifying the increase of O-GlcNAcylation, following hESC treatment with an O-GlcNAc hydrolase inhibitor. 24144119 2 25 theme mass 348:351 arg1 MS 367:368 MS 367:368 MS 367:368 Unfortunately, O-GlcNAc remains challenging to detect and quantify by shotgun mass spectrometry (MS) where it is time-consuming and tedious. 24144119 2 25 theme mass 348:351 arg1 spectrometry 353:364 shotgun mass spectrometry 340:364 shotgun mass spectrometry (MS) 340:369 Unfortunately, O-GlcNAc remains challenging to detect and quantify by shotgun mass spectrometry (MS) where it is time-consuming and tedious. 24144119 3 26 theme Multiple 449:456 arg1 Spectrometry 483:494 Multiple Reaction Monitoring Mass Spectrometry 449:494 Multiple Reaction Monitoring Mass Spectrometry (MRM-MS) 449:503 Here, we investigate the potential of Multiple Reaction Monitoring Mass Spectrometry (MRM-MS), a targeted MS method, to detect and quantify native O-GlcNAc modified peptides without extensive labeling and enrichment. 24144119 3 26 theme Multiple 449:456 arg1 MRM-MS 497:502 MRM-MS 497:502 MRM-MS 497:502 Here, we investigate the potential of Multiple Reaction Monitoring Mass Spectrometry (MRM-MS), a targeted MS method, to detect and quantify native O-GlcNAc modified peptides without extensive labeling and enrichment. 24144119 3 26 theme Multiple 449:456 arg1 method 520:525 a targeted MS method 506:525 a targeted MS method 506:525 Here, we investigate the potential of Multiple Reaction Monitoring Mass Spectrometry (MRM-MS), a targeted MS method, to detect and quantify native O-GlcNAc modified peptides without extensive labeling and enrichment. 24144119 0 27 theme mass 29:32 arg1 spectrometry 34:45 mass spectrometry 29:45 mass spectrometry 29:45 Multiple reaction monitoring mass spectrometry for the discovery and quantification of O-GlcNAc-modified proteins. 24144119 12 28 theme peptides/proteins 1847:1863 arg1 quantification 1810:1823 quantification 1810:1823 quantification 1810:1823 This could potentially facilitate rapid discovery and quantification of new O-GlcNAcylated peptides/proteins. 24144119 12 28 theme peptides/proteins 1847:1863 arg1 discovery 1796:1804 rapid discovery 1790:1804 rapid discovery 1790:1804 This could potentially facilitate rapid discovery and quantification of new O-GlcNAcylated peptides/proteins. 24144119 8 29 theme novel 1336:1340 arg1 peptide 1364:1370 a novel O-GlcNAcylated GSK-3β peptide 1334:1370 a novel O-GlcNAcylated GSK-3β peptide 1334:1370 Indeed, by only using gel electrophoresis to grossly enrich GSK-3β from whole cell lysate, we discover by MRM-MS a novel O-GlcNAcylated GSK-3β peptide, bearing 3 potential O-GlcNAcylation sites. 24144119 2 30 theme shotgun 340:346 arg1 MS 367:368 MS 367:368 MS 367:368 Unfortunately, O-GlcNAc remains challenging to detect and quantify by shotgun mass spectrometry (MS) where it is time-consuming and tedious. 24144119 2 30 theme shotgun 340:346 arg1 spectrometry 353:364 shotgun mass spectrometry 340:364 shotgun mass spectrometry (MS) 340:369 Unfortunately, O-GlcNAc remains challenging to detect and quantify by shotgun mass spectrometry (MS) where it is time-consuming and tedious. 24144119 9 31 theme O-GlcNAc 1520:1527 arg1 inhibitor 1539:1547 an O-GlcNAc hydrolase inhibitor 1517:1547 an O-GlcNAc hydrolase inhibitor 1517:1547 We confirm our finding by quantifying the increase of O-GlcNAcylation, following hESC treatment with an O-GlcNAc hydrolase inhibitor. 24144119 12 32 theme O-GlcNAcylated 1832:1845 arg1 peptides/proteins 1847:1863 new O-GlcNAcylated peptides/proteins 1828:1863 new O-GlcNAcylated peptides/proteins 1828:1863 This could potentially facilitate rapid discovery and quantification of new O-GlcNAcylated peptides/proteins. 24144119 8 33 theme potential 1383:1391 arg1 sites 1409:1413 3 potential O-GlcNAcylation sites 1381:1413 3 potential O-GlcNAcylation sites 1381:1413 Indeed, by only using gel electrophoresis to grossly enrich GSK-3β from whole cell lysate, we discover by MRM-MS a novel O-GlcNAcylated GSK-3β peptide, bearing 3 potential O-GlcNAcylation sites. 24144119 3 34 theme modified 567:574 arg1 peptides 576:583 native O-GlcNAc modified peptides 551:583 native O-GlcNAc modified peptides 551:583 Here, we investigate the potential of Multiple Reaction Monitoring Mass Spectrometry (MRM-MS), a targeted MS method, to detect and quantify native O-GlcNAc modified peptides without extensive labeling and enrichment. 24144119 9 35 with treatment 1502:1510 arg1 inhibitor 1539:1547 an O-GlcNAc hydrolase inhibitor 1517:1547 an O-GlcNAc hydrolase inhibitor 1517:1547 We confirm our finding by quantifying the increase of O-GlcNAcylation, following hESC treatment with an O-GlcNAc hydrolase inhibitor. 24144119 6 36 theme identical 1097:1105 arg1 site 1107:1110 identical site 1097:1110 identical site on proteins 1097:1122 Next, we apply this strategy to study glycogen synthase kinase-3 beta (GSK-3β), a kinase able to compete with O-GlcNAc transferase and modify identical site on proteins. 24144119 3 37 theme Mass 478:481 arg1 Spectrometry 483:494 Multiple Reaction Monitoring Mass Spectrometry 449:494 Multiple Reaction Monitoring Mass Spectrometry (MRM-MS) 449:503 Here, we investigate the potential of Multiple Reaction Monitoring Mass Spectrometry (MRM-MS), a targeted MS method, to detect and quantify native O-GlcNAc modified peptides without extensive labeling and enrichment. 24144119 3 37 theme Mass 478:481 arg1 MRM-MS 497:502 MRM-MS 497:502 MRM-MS 497:502 Here, we investigate the potential of Multiple Reaction Monitoring Mass Spectrometry (MRM-MS), a targeted MS method, to detect and quantify native O-GlcNAc modified peptides without extensive labeling and enrichment. 24144119 3 37 theme Mass 478:481 arg1 method 520:525 a targeted MS method 506:525 a targeted MS method 506:525 Here, we investigate the potential of Multiple Reaction Monitoring Mass Spectrometry (MRM-MS), a targeted MS method, to detect and quantify native O-GlcNAc modified peptides without extensive labeling and enrichment. 24144119 0 38 dep discovery 55:63 arg1 the 51:53 the 51:53 the 51:53 Multiple reaction monitoring mass spectrometry for the discovery and quantification of O-GlcNAc-modified proteins. 24144119 4 39 theme standard 672:679 arg1 peptide 696:702 a standard O-GlcNAcylated peptide 670:702 a standard O-GlcNAcylated peptide 670:702 We report the ability of MRM-MS to detect a standard O-GlcNAcylated peptide and show that the method is robust to quantify the amount of O-GlcNAcylated peptide with a method detection limit of 3 fmol. 24144119 1 40 theme cellular 237:244 arg1 processes 246:254 cellular processes 237:254 cellular processes 237:254 O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification regulating proteins involved in a variety of cellular processes and diseases. 24144119 12 41 theme rapid 1790:1794 arg1 discovery 1796:1804 rapid discovery 1790:1804 rapid discovery 1790:1804 This could potentially facilitate rapid discovery and quantification of new O-GlcNAcylated peptides/proteins. 24144119 3 42 theme Spectrometry 483:494 arg1 potential 436:444 the potential 432:444 the potential of Multiple Reaction Monitoring Mass Spectrometry (MRM-MS), a targeted MS method, to detect and quantify native O-GlcNAc modified peptides without extensive labeling and enrichment 432:625 Here, we investigate the potential of Multiple Reaction Monitoring Mass Spectrometry (MRM-MS), a targeted MS method, to detect and quantify native O-GlcNAc modified peptides without extensive labeling and enrichment. 24144119 8 43 theme whole 1293:1297 arg1 lysate 1304:1309 whole cell lysate 1293:1309 whole cell lysate 1293:1309 Indeed, by only using gel electrophoresis to grossly enrich GSK-3β from whole cell lysate, we discover by MRM-MS a novel O-GlcNAcylated GSK-3β peptide, bearing 3 potential O-GlcNAcylation sites. 24144119 8 44 theme O-GlcNAcylation 1393:1407 arg1 sites 1409:1413 3 potential O-GlcNAcylation sites 1381:1413 3 potential O-GlcNAcylation sites 1381:1413 Indeed, by only using gel electrophoresis to grossly enrich GSK-3β from whole cell lysate, we discover by MRM-MS a novel O-GlcNAcylated GSK-3β peptide, bearing 3 potential O-GlcNAcylation sites. 24144119 3 45 theme extensive 593:601 arg1 labeling 603:610 extensive labeling 593:610 extensive labeling 593:610 Here, we investigate the potential of Multiple Reaction Monitoring Mass Spectrometry (MRM-MS), a targeted MS method, to detect and quantify native O-GlcNAc modified peptides without extensive labeling and enrichment. 24144119 6 46 theme O-GlcNAc 1065:1072 arg1 transferase 1074:1084 O-GlcNAc transferase 1065:1084 O-GlcNAc transferase 1065:1084 Next, we apply this strategy to study glycogen synthase kinase-3 beta (GSK-3β), a kinase able to compete with O-GlcNAc transferase and modify identical site on proteins. 24144119 4 47 theme fmol 823:826 arg1 limit 812:816 a method detection limit 793:816 a method detection limit of 3 fmol 793:826 We report the ability of MRM-MS to detect a standard O-GlcNAcylated peptide and show that the method is robust to quantify the amount of O-GlcNAcylated peptide with a method detection limit of 3 fmol. 24144119 6 48 from site 1107:1110 arg1 proteins 1115:1122 proteins 1115:1122 proteins 1115:1122 Next, we apply this strategy to study glycogen synthase kinase-3 beta (GSK-3β), a kinase able to compete with O-GlcNAc transferase and modify identical site on proteins. 24144119 3 49 theme targeted 508:515 arg1 method 520:525 a targeted MS method 506:525 a targeted MS method 506:525 Here, we investigate the potential of Multiple Reaction Monitoring Mass Spectrometry (MRM-MS), a targeted MS method, to detect and quantify native O-GlcNAc modified peptides without extensive labeling and enrichment. 24144119 3 49 theme targeted 508:515 arg1 Spectrometry 483:494 Multiple Reaction Monitoring Mass Spectrometry 449:494 Multiple Reaction Monitoring Mass Spectrometry (MRM-MS) 449:503 Here, we investigate the potential of Multiple Reaction Monitoring Mass Spectrometry (MRM-MS), a targeted MS method, to detect and quantify native O-GlcNAc modified peptides without extensive labeling and enrichment. 24144119 8 50 from lysate 1304:1309 arg1 GSK-3β 1281:1286 GSK-3β 1281:1286 GSK-3β from whole cell lysate 1281:1309 Indeed, by only using gel electrophoresis to grossly enrich GSK-3β from whole cell lysate, we discover by MRM-MS a novel O-GlcNAcylated GSK-3β peptide, bearing 3 potential O-GlcNAcylation sites. 24144119 12 51 theme new 1828:1830 arg1 peptides/proteins 1847:1863 new O-GlcNAcylated peptides/proteins 1828:1863 new O-GlcNAcylated peptides/proteins 1828:1863 This could potentially facilitate rapid discovery and quantification of new O-GlcNAcylated peptides/proteins. 24144119 11 52 theme first 1681:1685 arg1 report 1687:1692 the first report 1677:1692 the first report utilizing MRM-MS to detect native O-GlcNAc modified peptides 1677:1753 To the best of our knowledge, this is the first report utilizing MRM-MS to detect native O-GlcNAc modified peptides. 24144119 11 52 theme first 1681:1685 arg1 this 1669:1672 this 1669:1672 this 1669:1672 To the best of our knowledge, this is the first report utilizing MRM-MS to detect native O-GlcNAc modified peptides. 24144119 4 53 theme method 795:800 arg1 limit 812:816 a method detection limit 793:816 a method detection limit of 3 fmol 793:826 We report the ability of MRM-MS to detect a standard O-GlcNAcylated peptide and show that the method is robust to quantify the amount of O-GlcNAcylated peptide with a method detection limit of 3 fmol. 24144119 6 54 theme kinase-3 1011:1018 arg1 kinase 1037:1042 a kinase 1035:1042 a kinase able to compete with O-GlcNAc transferase and modify identical site on proteins 1035:1122 Next, we apply this strategy to study glycogen synthase kinase-3 beta (GSK-3β), a kinase able to compete with O-GlcNAc transferase and modify identical site on proteins. 24144119 6 54 theme kinase-3 1011:1018 arg1 GSK-3β 1026:1031 GSK-3β 1026:1031 GSK-3β 1026:1031 Next, we apply this strategy to study glycogen synthase kinase-3 beta (GSK-3β), a kinase able to compete with O-GlcNAc transferase and modify identical site on proteins. 24144119 6 54 theme kinase-3 1011:1018 arg1 beta 1020:1023 glycogen synthase kinase-3 beta 993:1023 glycogen synthase kinase-3 beta (GSK-3β) 993:1032 Next, we apply this strategy to study glycogen synthase kinase-3 beta (GSK-3β), a kinase able to compete with O-GlcNAc transferase and modify identical site on proteins. 24144119 1 55 theme O-linked 115:122 arg1 modification 179:190 a post-translational modification 158:190 a post-translational modification regulating proteins involved in a variety of cellular processes and diseases 158:267 O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification regulating proteins involved in a variety of cellular processes and diseases. 24144119 1 55 theme O-linked 115:122 arg1 O-GlcNAc 145:152 O-GlcNAc 145:152 O-GlcNAc 145:152 O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification regulating proteins involved in a variety of cellular processes and diseases. 24144119 1 55 theme O-linked 115:122 arg1 N-acetylglucosamine 124:142 O-linked N-acetylglucosamine 115:142 O-linked N-acetylglucosamine (O-GlcNAc) 115:153 O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification regulating proteins involved in a variety of cellular processes and diseases. 24144119 8 56 theme cell 1299:1302 arg1 lysate 1304:1309 whole cell lysate 1293:1309 whole cell lysate 1293:1309 Indeed, by only using gel electrophoresis to grossly enrich GSK-3β from whole cell lysate, we discover by MRM-MS a novel O-GlcNAcylated GSK-3β peptide, bearing 3 potential O-GlcNAcylation sites. 24144119 8 57 theme GSK-3β 1357:1362 arg1 peptide 1364:1370 a novel O-GlcNAcylated GSK-3β peptide 1334:1370 a novel O-GlcNAcylated GSK-3β peptide 1334:1370 Indeed, by only using gel electrophoresis to grossly enrich GSK-3β from whole cell lysate, we discover by MRM-MS a novel O-GlcNAcylated GSK-3β peptide, bearing 3 potential O-GlcNAcylation sites. 24144119 5 58 theme O-GlcNAcylated 912:925 arg1 peptide 927:933 the O-GlcNAcylated peptide 908:933 the O-GlcNAcylated peptide 908:933 In addition, when diluted by 100-fold in a trypsin-digested whole cell lysate, the O-GlcNAcylated peptide remains detectable. 24144119 1 59 theme diseases 260:267 arg1 diseases 260:267 diseases 260:267 diseases 260:267 O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification regulating proteins involved in a variety of cellular processes and diseases. 24144119 1 59 theme diseases 260:267 arg1 variety 226:232 a variety 224:232 a variety of cellular processes and diseases 224:267 O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification regulating proteins involved in a variety of cellular processes and diseases. 24144119 1 59 theme diseases 260:267 arg1 processes 246:254 cellular processes 237:254 cellular processes 237:254 O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification regulating proteins involved in a variety of cellular processes and diseases. 24144119 1 60 link O-linked 115:122 arg1 modification 179:190 a post-translational modification 158:190 a post-translational modification regulating proteins involved in a variety of cellular processes and diseases 158:267 O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification regulating proteins involved in a variety of cellular processes and diseases. 24144119 1 60 link O-linked 115:122 arg1 O-GlcNAc 145:152 O-GlcNAc 145:152 O-GlcNAc 145:152 O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification regulating proteins involved in a variety of cellular processes and diseases. 24144119 1 60 link O-linked 115:122 arg1 N-acetylglucosamine 124:142 O-linked N-acetylglucosamine 115:142 O-linked N-acetylglucosamine (O-GlcNAc) 115:153 O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification regulating proteins involved in a variety of cellular processes and diseases. 24144119 1 61 theme processes 246:254 arg1 diseases 260:267 diseases 260:267 diseases 260:267 O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification regulating proteins involved in a variety of cellular processes and diseases. 24144119 1 61 theme processes 246:254 arg1 variety 226:232 a variety 224:232 a variety of cellular processes and diseases 224:267 O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification regulating proteins involved in a variety of cellular processes and diseases. 24144119 1 61 theme processes 246:254 arg1 processes 246:254 cellular processes 237:254 cellular processes 237:254 O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification regulating proteins involved in a variety of cellular processes and diseases. 24144119 5 62 theme trypsin-digested 872:887 arg1 lysate 900:905 a trypsin-digested whole cell lysate 870:905 a trypsin-digested whole cell lysate 870:905 In addition, when diluted by 100-fold in a trypsin-digested whole cell lysate, the O-GlcNAcylated peptide remains detectable. 24144119 6 63 theme able 1044:1047 arg1 kinase 1037:1042 a kinase 1035:1042 a kinase able to compete with O-GlcNAc transferase and modify identical site on proteins 1035:1122 Next, we apply this strategy to study glycogen synthase kinase-3 beta (GSK-3β), a kinase able to compete with O-GlcNAc transferase and modify identical site on proteins. 24144119 6 63 theme able 1044:1047 arg1 beta 1020:1023 glycogen synthase kinase-3 beta 993:1023 glycogen synthase kinase-3 beta (GSK-3β) 993:1032 Next, we apply this strategy to study glycogen synthase kinase-3 beta (GSK-3β), a kinase able to compete with O-GlcNAc transferase and modify identical site on proteins. 24144119 6 64 theme synthase 1002:1009 arg1 kinase-3 1011:1018 glycogen synthase kinase-3 993:1018 glycogen synthase kinase-3 beta (GSK-3β) 993:1032 Next, we apply this strategy to study glycogen synthase kinase-3 beta (GSK-3β), a kinase able to compete with O-GlcNAc transferase and modify identical site on proteins. 24144119 7 65 theme stem 1202:1205 arg1 hESC 1214:1217 hESC 1214:1217 hESC 1214:1217 We demonstrate that GSK-3β is itself modified by O-GlcNAc in human embryonic stem cells (hESC). 24144119 7 65 theme stem 1202:1205 arg1 cells 1207:1211 human embryonic stem cells 1186:1211 human embryonic stem cells (hESC) 1186:1218 We demonstrate that GSK-3β is itself modified by O-GlcNAc in human embryonic stem cells (hESC). 24144119 4 66 theme detection 802:810 arg1 limit 812:816 a method detection limit 793:816 a method detection limit of 3 fmol 793:826 We report the ability of MRM-MS to detect a standard O-GlcNAcylated peptide and show that the method is robust to quantify the amount of O-GlcNAcylated peptide with a method detection limit of 3 fmol. 24144119 1 67 theme post-translational 160:177 arg1 modification 179:190 a post-translational modification 158:190 a post-translational modification regulating proteins involved in a variety of cellular processes and diseases 158:267 O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification regulating proteins involved in a variety of cellular processes and diseases. 24144119 1 67 theme post-translational 160:177 arg1 N-acetylglucosamine 124:142 O-linked N-acetylglucosamine 115:142 O-linked N-acetylglucosamine (O-GlcNAc) 115:153 O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification regulating proteins involved in a variety of cellular processes and diseases. 24144119 6 68 theme glycogen 993:1000 arg1 kinase-3 1011:1018 glycogen synthase kinase-3 993:1018 glycogen synthase kinase-3 beta (GSK-3β) 993:1032 Next, we apply this strategy to study glycogen synthase kinase-3 beta (GSK-3β), a kinase able to compete with O-GlcNAc transferase and modify identical site on proteins. 28536142 6 0 theme significant 904:914 arg1 downregulation 916:929 significant downregulation 904:929 significant downregulation of p38 MAPK activity 904:950 The tumors grown in Ogt-Tg/+ mice showed significant downregulation of p38 MAPK activity and upregulation of the ERK1/2 signaling pathway. 28536142 9 1 theme tumor 1667:1671 arg1 proliferation 1673:1685 tumor proliferation 1667:1685 tumor proliferation 1667:1685 These data reveal that elevated O-GlcNAcylation in the TME reduces the production of inflammatory cytokines and promotes cancer progression through downregulation of p38 MAPK activity and subsequent upregulation of the ERK1/2 signaling pathway.Implications: The reduced production of inflammatory cytokines by augmented O-GlcNAcylation in the TME, mainly macrophages, promotes tumor proliferation through the inhibition of p38 MAPK and suggests a possible cause of increased morbidity and mortality rates for various cancers in diabetic patients. 28536142 11 2 theme ©2017 1869:1873 arg1 AACR 1875:1878 ©2017 AACR 1869:1878 ©2017 AACR. 1869:1879 ©2017 AACR. 28536142 4 3 from O-GlcNAcylation 698:712 arg1 TME 721:723 the TME 717:723 the TME 717:723 Here, B16 melanoma cells were subcutaneously transplanted into O-GlcNAc transferase transgenic (Ogt-Tg) mice exhibiting elevated O-GlcNAcylation to examine the effect of O-GlcNAcylation in the TME on tumor progression. 28536142 8 4 theme NF-κB 1157:1161 arg1 Activation 1143:1152 Activation 1143:1152 Activation of NF-κB, a key regulator in the cytokine production, 1143:1206 Activation of NF-κB, a key regulator in the cytokine production, was downregulated in the macrophages of the tumor tissues grown in Ogt-Tg/+ mice. 28536142 4 5 theme transferase 600:610 arg1 mice 632:635 O-GlcNAc transferase transgenic (Ogt-Tg) mice 591:635 O-GlcNAc transferase transgenic (Ogt-Tg) mice exhibiting elevated O-GlcNAcylation 591:671 Here, B16 melanoma cells were subcutaneously transplanted into O-GlcNAc transferase transgenic (Ogt-Tg) mice exhibiting elevated O-GlcNAcylation to examine the effect of O-GlcNAcylation in the TME on tumor progression. 28536142 4 6 from effect 688:693 arg1 TME 721:723 the TME 717:723 the TME 717:723 Here, B16 melanoma cells were subcutaneously transplanted into O-GlcNAc transferase transgenic (Ogt-Tg) mice exhibiting elevated O-GlcNAcylation to examine the effect of O-GlcNAcylation in the TME on tumor progression. 28536142 4 6 from effect 688:693 arg1 progression 734:744 tumor progression 728:744 tumor progression 728:744 Here, B16 melanoma cells were subcutaneously transplanted into O-GlcNAc transferase transgenic (Ogt-Tg) mice exhibiting elevated O-GlcNAcylation to examine the effect of O-GlcNAcylation in the TME on tumor progression. 28536142 0 7 theme Augmented 0:8 arg1 O-GlcNAcylation 14:28 Augmented TME O-GlcNAcylation 0:28 Augmented TME O-GlcNAcylation 0:28 Augmented TME O-GlcNAcylation Promotes Tumor Proliferation through the Inhibition of p38 MAPK. 28536142 9 8 theme p38 1713:1715 arg1 MAPK 1717:1720 p38 MAPK 1713:1720 p38 MAPK 1713:1720 These data reveal that elevated O-GlcNAcylation in the TME reduces the production of inflammatory cytokines and promotes cancer progression through downregulation of p38 MAPK activity and subsequent upregulation of the ERK1/2 signaling pathway.Implications: The reduced production of inflammatory cytokines by augmented O-GlcNAcylation in the TME, mainly macrophages, promotes tumor proliferation through the inhibition of p38 MAPK and suggests a possible cause of increased morbidity and mortality rates for various cancers in diabetic patients. 28536142 2 9 theme cancer 326:331 arg1 phenotypes 333:342 various cancer phenotypes 318:342 various cancer phenotypes 318:342 Recent studies indicate that increased O-GlcNAcylation is a general feature in cancer and contributes to various cancer phenotypes, including cell proliferation, survival, invasion, metastasis, and energy metabolism. 28536142 2 9 theme cancer 326:331 arg1 survival 375:382 survival 375:382 survival 375:382 Recent studies indicate that increased O-GlcNAcylation is a general feature in cancer and contributes to various cancer phenotypes, including cell proliferation, survival, invasion, metastasis, and energy metabolism. 28536142 2 9 theme cancer 326:331 arg1 invasion 385:392 invasion 385:392 invasion 385:392 Recent studies indicate that increased O-GlcNAcylation is a general feature in cancer and contributes to various cancer phenotypes, including cell proliferation, survival, invasion, metastasis, and energy metabolism. 28536142 2 9 theme cancer 326:331 arg1 metabolism 418:427 energy metabolism 411:427 energy metabolism 411:427 Recent studies indicate that increased O-GlcNAcylation is a general feature in cancer and contributes to various cancer phenotypes, including cell proliferation, survival, invasion, metastasis, and energy metabolism. 28536142 2 9 theme cancer 326:331 arg1 proliferation 360:372 cell proliferation 355:372 cell proliferation 355:372 Recent studies indicate that increased O-GlcNAcylation is a general feature in cancer and contributes to various cancer phenotypes, including cell proliferation, survival, invasion, metastasis, and energy metabolism. 28536142 2 9 theme cancer 326:331 arg1 metastasis 395:404 metastasis 395:404 metastasis 395:404 Recent studies indicate that increased O-GlcNAcylation is a general feature in cancer and contributes to various cancer phenotypes, including cell proliferation, survival, invasion, metastasis, and energy metabolism. 28536142 1 10 theme cellular 193:200 arg1 signaling 202:210 cellular signaling 193:210 cellular signaling 193:210 O-GlcNAcylation is a dynamic O-linked glycosylation event that plays a crucial role in regulating cellular signaling. 28536142 7 11 theme tumor 1082:1086 arg1 tissues 1088:1094 the tumor tissues 1078:1094 the tumor tissues from Ogt-Tg/+ mice 1078:1113 In addition, proinflammatory cytokine production was significantly lower in the tumor tissues from Ogt-Tg/+ mice than in those from WT mice. 28536142 5 12 theme wild-type 842:850 arg1 mice 857:860 wild-type (WT) mice 842:860 wild-type (WT) mice 842:860 In this model system, B16 tumor growth was significantly higher in Ogt-Tg/+ mice compared with wild-type (WT) mice. 28536142 8 13 theme tissues 1258:1264 arg1 macrophages 1233:1243 the macrophages 1229:1243 the macrophages of the tumor tissues grown in Ogt-Tg/+ mice 1229:1287 Activation of NF-κB, a key regulator in the cytokine production, was downregulated in the macrophages of the tumor tissues grown in Ogt-Tg/+ mice. 28536142 2 14 theme increased 242:250 arg1 O-GlcNAcylation 252:266 increased O-GlcNAcylation 242:266 increased O-GlcNAcylation 242:266 Recent studies indicate that increased O-GlcNAcylation is a general feature in cancer and contributes to various cancer phenotypes, including cell proliferation, survival, invasion, metastasis, and energy metabolism. 28536142 2 14 theme increased 242:250 arg1 feature 281:287 a general feature 271:287 a general feature in cancer 271:297 Recent studies indicate that increased O-GlcNAcylation is a general feature in cancer and contributes to various cancer phenotypes, including cell proliferation, survival, invasion, metastasis, and energy metabolism. 28536142 9 15 theme subsequent 1478:1487 arg1 upregulation 1489:1500 subsequent upregulation 1478:1500 subsequent upregulation of the ERK1/2 signaling pathway.Implications: The reduced production of inflammatory cytokines by augmented O-GlcNAcylation in the TME, mainly macrophages 1478:1655 These data reveal that elevated O-GlcNAcylation in the TME reduces the production of inflammatory cytokines and promotes cancer progression through downregulation of p38 MAPK activity and subsequent upregulation of the ERK1/2 signaling pathway.Implications: The reduced production of inflammatory cytokines by augmented O-GlcNAcylation in the TME, mainly macrophages, promotes tumor proliferation through the inhibition of p38 MAPK and suggests a possible cause of increased morbidity and mortality rates for various cancers in diabetic patients. 28536142 6 16 theme MAPK 938:941 arg1 activity 943:950 p38 MAPK activity 934:950 p38 MAPK activity 934:950 The tumors grown in Ogt-Tg/+ mice showed significant downregulation of p38 MAPK activity and upregulation of the ERK1/2 signaling pathway. 28536142 1 17 theme O-linked 124:131 arg1 O-GlcNAcylation 95:109 O-GlcNAcylation 95:109 O-GlcNAcylation 95:109 O-GlcNAcylation is a dynamic O-linked glycosylation event that plays a crucial role in regulating cellular signaling. 28536142 1 17 theme O-linked 124:131 arg1 event 147:151 a dynamic O-linked glycosylation event 114:151 a dynamic O-linked glycosylation event that plays a crucial role in regulating cellular signaling 114:210 O-GlcNAcylation is a dynamic O-linked glycosylation event that plays a crucial role in regulating cellular signaling. 28536142 9 18 theme increased 1755:1763 arg1 rates 1789:1793 increased morbidity and mortality rates 1755:1793 increased morbidity and mortality rates for various cancers in diabetic patients 1755:1834 These data reveal that elevated O-GlcNAcylation in the TME reduces the production of inflammatory cytokines and promotes cancer progression through downregulation of p38 MAPK activity and subsequent upregulation of the ERK1/2 signaling pathway.Implications: The reduced production of inflammatory cytokines by augmented O-GlcNAcylation in the TME, mainly macrophages, promotes tumor proliferation through the inhibition of p38 MAPK and suggests a possible cause of increased morbidity and mortality rates for various cancers in diabetic patients. 28536142 2 19 theme general 273:279 arg1 O-GlcNAcylation 252:266 increased O-GlcNAcylation 242:266 increased O-GlcNAcylation 242:266 Recent studies indicate that increased O-GlcNAcylation is a general feature in cancer and contributes to various cancer phenotypes, including cell proliferation, survival, invasion, metastasis, and energy metabolism. 28536142 2 19 theme general 273:279 arg1 feature 281:287 a general feature 271:287 a general feature in cancer 271:297 Recent studies indicate that increased O-GlcNAcylation is a general feature in cancer and contributes to various cancer phenotypes, including cell proliferation, survival, invasion, metastasis, and energy metabolism. 28536142 9 20 theme ERK1/2 1509:1514 arg1 pathway.Implications 1526:1545 the ERK1/2 signaling pathway.Implications 1505:1545 the ERK1/2 signaling pathway.Implications 1505:1545 These data reveal that elevated O-GlcNAcylation in the TME reduces the production of inflammatory cytokines and promotes cancer progression through downregulation of p38 MAPK activity and subsequent upregulation of the ERK1/2 signaling pathway.Implications: The reduced production of inflammatory cytokines by augmented O-GlcNAcylation in the TME, mainly macrophages, promotes tumor proliferation through the inhibition of p38 MAPK and suggests a possible cause of increased morbidity and mortality rates for various cancers in diabetic patients. 28536142 9 20 theme ERK1/2 1509:1514 arg1 macrophages 1645:1655 macrophages 1645:1655 macrophages 1645:1655 These data reveal that elevated O-GlcNAcylation in the TME reduces the production of inflammatory cytokines and promotes cancer progression through downregulation of p38 MAPK activity and subsequent upregulation of the ERK1/2 signaling pathway.Implications: The reduced production of inflammatory cytokines by augmented O-GlcNAcylation in the TME, mainly macrophages, promotes tumor proliferation through the inhibition of p38 MAPK and suggests a possible cause of increased morbidity and mortality rates for various cancers in diabetic patients. 28536142 4 21 theme tumor 728:732 arg1 progression 734:744 tumor progression 728:744 tumor progression 728:744 Here, B16 melanoma cells were subcutaneously transplanted into O-GlcNAc transferase transgenic (Ogt-Tg) mice exhibiting elevated O-GlcNAcylation to examine the effect of O-GlcNAcylation in the TME on tumor progression. 28536142 4 22 theme O-GlcNAcylation 698:712 arg1 effect 688:693 the effect 684:693 the effect of O-GlcNAcylation in the TME on tumor progression 684:744 Here, B16 melanoma cells were subcutaneously transplanted into O-GlcNAc transferase transgenic (Ogt-Tg) mice exhibiting elevated O-GlcNAcylation to examine the effect of O-GlcNAcylation in the TME on tumor progression. 28536142 9 23 theme pathway.Implications 1526:1545 arg1 upregulation 1489:1500 subsequent upregulation 1478:1500 subsequent upregulation of the ERK1/2 signaling pathway.Implications: The reduced production of inflammatory cytokines by augmented O-GlcNAcylation in the TME, mainly macrophages 1478:1655 These data reveal that elevated O-GlcNAcylation in the TME reduces the production of inflammatory cytokines and promotes cancer progression through downregulation of p38 MAPK activity and subsequent upregulation of the ERK1/2 signaling pathway.Implications: The reduced production of inflammatory cytokines by augmented O-GlcNAcylation in the TME, mainly macrophages, promotes tumor proliferation through the inhibition of p38 MAPK and suggests a possible cause of increased morbidity and mortality rates for various cancers in diabetic patients. 28536142 9 23 theme pathway.Implications 1526:1545 arg1 downregulation 1438:1451 downregulation 1438:1451 downregulation of p38 MAPK activity 1438:1472 These data reveal that elevated O-GlcNAcylation in the TME reduces the production of inflammatory cytokines and promotes cancer progression through downregulation of p38 MAPK activity and subsequent upregulation of the ERK1/2 signaling pathway.Implications: The reduced production of inflammatory cytokines by augmented O-GlcNAcylation in the TME, mainly macrophages, promotes tumor proliferation through the inhibition of p38 MAPK and suggests a possible cause of increased morbidity and mortality rates for various cancers in diabetic patients. 28536142 9 24 theme rates 1789:1793 arg1 cause 1746:1750 a possible cause 1735:1750 a possible cause of increased morbidity and mortality rates for various cancers in diabetic patients 1735:1834 These data reveal that elevated O-GlcNAcylation in the TME reduces the production of inflammatory cytokines and promotes cancer progression through downregulation of p38 MAPK activity and subsequent upregulation of the ERK1/2 signaling pathway.Implications: The reduced production of inflammatory cytokines by augmented O-GlcNAcylation in the TME, mainly macrophages, promotes tumor proliferation through the inhibition of p38 MAPK and suggests a possible cause of increased morbidity and mortality rates for various cancers in diabetic patients. 28536142 0 25 theme p38 85:87 arg1 MAPK 89:92 p38 MAPK 85:92 p38 MAPK 85:92 Augmented TME O-GlcNAcylation Promotes Tumor Proliferation through the Inhibition of p38 MAPK. 28536142 1 26 theme crucial 166:172 arg1 role 174:177 a crucial role 164:177 a crucial role 164:177 O-GlcNAcylation is a dynamic O-linked glycosylation event that plays a crucial role in regulating cellular signaling. 28536142 6 27 theme pathway 993:999 arg1 upregulation 956:967 upregulation 956:967 upregulation of the ERK1/2 signaling pathway 956:999 The tumors grown in Ogt-Tg/+ mice showed significant downregulation of p38 MAPK activity and upregulation of the ERK1/2 signaling pathway. 28536142 6 27 theme pathway 993:999 arg1 downregulation 916:929 significant downregulation 904:929 significant downregulation of p38 MAPK activity 904:950 The tumors grown in Ogt-Tg/+ mice showed significant downregulation of p38 MAPK activity and upregulation of the ERK1/2 signaling pathway. 28536142 9 28 theme various 1799:1805 arg1 cancers 1807:1813 various cancers 1799:1813 various cancers in diabetic patients 1799:1834 These data reveal that elevated O-GlcNAcylation in the TME reduces the production of inflammatory cytokines and promotes cancer progression through downregulation of p38 MAPK activity and subsequent upregulation of the ERK1/2 signaling pathway.Implications: The reduced production of inflammatory cytokines by augmented O-GlcNAcylation in the TME, mainly macrophages, promotes tumor proliferation through the inhibition of p38 MAPK and suggests a possible cause of increased morbidity and mortality rates for various cancers in diabetic patients. 28536142 6 29 theme ERK1/2 976:981 arg1 pathway 993:999 the ERK1/2 signaling pathway 972:999 the ERK1/2 signaling pathway 972:999 The tumors grown in Ogt-Tg/+ mice showed significant downregulation of p38 MAPK activity and upregulation of the ERK1/2 signaling pathway. 28536142 5 30 theme model 755:759 arg1 system 761:766 this model system 750:766 this model system 750:766 In this model system, B16 tumor growth was significantly higher in Ogt-Tg/+ mice compared with wild-type (WT) mice. 28536142 9 31 theme inflammatory 1574:1585 arg1 cytokines 1587:1595 inflammatory cytokines 1574:1595 inflammatory cytokines 1574:1595 These data reveal that elevated O-GlcNAcylation in the TME reduces the production of inflammatory cytokines and promotes cancer progression through downregulation of p38 MAPK activity and subsequent upregulation of the ERK1/2 signaling pathway.Implications: The reduced production of inflammatory cytokines by augmented O-GlcNAcylation in the TME, mainly macrophages, promotes tumor proliferation through the inhibition of p38 MAPK and suggests a possible cause of increased morbidity and mortality rates for various cancers in diabetic patients. 28536142 5 32 theme Ogt-Tg/+ 814:821 arg1 mice 823:826 Ogt-Tg/+ mice 814:826 Ogt-Tg/+ mice 814:826 In this model system, B16 tumor growth was significantly higher in Ogt-Tg/+ mice compared with wild-type (WT) mice. 28536142 4 33 theme melanoma 538:545 arg1 cells 547:551 B16 melanoma cells 534:551 B16 melanoma cells 534:551 Here, B16 melanoma cells were subcutaneously transplanted into O-GlcNAc transferase transgenic (Ogt-Tg) mice exhibiting elevated O-GlcNAcylation to examine the effect of O-GlcNAcylation in the TME on tumor progression. 28536142 2 34 from feature 281:287 arg1 cancer 292:297 cancer 292:297 cancer 292:297 Recent studies indicate that increased O-GlcNAcylation is a general feature in cancer and contributes to various cancer phenotypes, including cell proliferation, survival, invasion, metastasis, and energy metabolism. 28536142 7 35 from mice 1110:1113 arg1 tissues 1088:1094 the tumor tissues 1078:1094 the tumor tissues from Ogt-Tg/+ mice 1078:1113 In addition, proinflammatory cytokine production was significantly lower in the tumor tissues from Ogt-Tg/+ mice than in those from WT mice. 28536142 3 36 theme O-GlcNAcylation 451:465 arg1 role 443:446 the role 439:446 the role of O-GlcNAcylation in the tumor microenvironment (TME) 439:501 However, the role of O-GlcNAcylation in the tumor microenvironment (TME) is not fully elucidated. 28536142 0 37 theme Tumor 39:43 arg1 Proliferation 45:57 Tumor Proliferation 39:57 Tumor Proliferation 39:57 Augmented TME O-GlcNAcylation Promotes Tumor Proliferation through the Inhibition of p38 MAPK. 28536142 2 38 theme Recent 213:218 arg1 studies 220:226 Recent studies 213:226 Recent studies 213:226 Recent studies indicate that increased O-GlcNAcylation is a general feature in cancer and contributes to various cancer phenotypes, including cell proliferation, survival, invasion, metastasis, and energy metabolism. 28536142 4 39 theme transgenic 612:621 arg1 mice 632:635 O-GlcNAc transferase transgenic (Ogt-Tg) mice 591:635 O-GlcNAc transferase transgenic (Ogt-Tg) mice exhibiting elevated O-GlcNAcylation 591:671 Here, B16 melanoma cells were subcutaneously transplanted into O-GlcNAc transferase transgenic (Ogt-Tg) mice exhibiting elevated O-GlcNAcylation to examine the effect of O-GlcNAcylation in the TME on tumor progression. 28536142 4 40 from TME 721:723 arg1 effect 688:693 the effect 684:693 the effect of O-GlcNAcylation in the TME on tumor progression 684:744 Here, B16 melanoma cells were subcutaneously transplanted into O-GlcNAc transferase transgenic (Ogt-Tg) mice exhibiting elevated O-GlcNAcylation to examine the effect of O-GlcNAcylation in the TME on tumor progression. 28536142 9 41 theme inflammatory 1375:1386 arg1 cytokines 1388:1396 inflammatory cytokines 1375:1396 inflammatory cytokines 1375:1396 These data reveal that elevated O-GlcNAcylation in the TME reduces the production of inflammatory cytokines and promotes cancer progression through downregulation of p38 MAPK activity and subsequent upregulation of the ERK1/2 signaling pathway.Implications: The reduced production of inflammatory cytokines by augmented O-GlcNAcylation in the TME, mainly macrophages, promotes tumor proliferation through the inhibition of p38 MAPK and suggests a possible cause of increased morbidity and mortality rates for various cancers in diabetic patients. 28536142 4 42 theme Ogt-Tg 624:629 arg1 mice 632:635 O-GlcNAc transferase transgenic (Ogt-Tg) mice 591:635 O-GlcNAc transferase transgenic (Ogt-Tg) mice exhibiting elevated O-GlcNAcylation 591:671 Here, B16 melanoma cells were subcutaneously transplanted into O-GlcNAc transferase transgenic (Ogt-Tg) mice exhibiting elevated O-GlcNAcylation to examine the effect of O-GlcNAcylation in the TME on tumor progression. 28536142 5 43 theme B16 769:771 arg1 growth 779:784 B16 tumor growth 769:784 B16 tumor growth 769:784 In this model system, B16 tumor growth was significantly higher in Ogt-Tg/+ mice compared with wild-type (WT) mice. 28536142 8 44 from regulator 1170:1178 arg1 production 1196:1205 the cytokine production 1183:1205 the cytokine production 1183:1205 Activation of NF-κB, a key regulator in the cytokine production, was downregulated in the macrophages of the tumor tissues grown in Ogt-Tg/+ mice. 28536142 9 45 theme cancer 1411:1416 arg1 progression 1418:1428 cancer progression 1411:1428 cancer progression 1411:1428 These data reveal that elevated O-GlcNAcylation in the TME reduces the production of inflammatory cytokines and promotes cancer progression through downregulation of p38 MAPK activity and subsequent upregulation of the ERK1/2 signaling pathway.Implications: The reduced production of inflammatory cytokines by augmented O-GlcNAcylation in the TME, mainly macrophages, promotes tumor proliferation through the inhibition of p38 MAPK and suggests a possible cause of increased morbidity and mortality rates for various cancers in diabetic patients. 28536142 6 46 theme Ogt-Tg/+ 883:890 arg1 mice 892:895 Ogt-Tg/+ mice 883:895 Ogt-Tg/+ mice 883:895 The tumors grown in Ogt-Tg/+ mice showed significant downregulation of p38 MAPK activity and upregulation of the ERK1/2 signaling pathway. 28536142 4 47 theme O-GlcNAc 591:598 arg1 transferase 600:610 O-GlcNAc transferase 591:610 O-GlcNAc transferase transgenic (Ogt-Tg) mice exhibiting elevated O-GlcNAcylation 591:671 Here, B16 melanoma cells were subcutaneously transplanted into O-GlcNAc transferase transgenic (Ogt-Tg) mice exhibiting elevated O-GlcNAcylation to examine the effect of O-GlcNAcylation in the TME on tumor progression. 28536142 7 48 theme Ogt-Tg/+ 1101:1108 arg1 mice 1110:1113 Ogt-Tg/+ mice 1101:1113 Ogt-Tg/+ mice 1101:1113 In addition, proinflammatory cytokine production was significantly lower in the tumor tissues from Ogt-Tg/+ mice than in those from WT mice. 28536142 10 49 dep Res 1848:1850 arg1 9 1856:1856 9 1856:1856 9 1856:1856 Mol Cancer Res; 15(9); 1287-98. 28536142 10 49 dep Res 1848:1850 arg1 1287-98 1860:1866 1287-98 1860:1866 1287-98 1860:1866 Mol Cancer Res; 15(9); 1287-98. 28536142 10 49 dep Res 1848:1850 arg1 15 1853:1854 15 1853:1854 15 1853:1854 Mol Cancer Res; 15(9); 1287-98. 28536142 5 50 theme tumor 773:777 arg1 growth 779:784 B16 tumor growth 769:784 B16 tumor growth 769:784 In this model system, B16 tumor growth was significantly higher in Ogt-Tg/+ mice compared with wild-type (WT) mice. 28536142 8 51 theme key 1166:1168 arg1 NF-κB 1157:1161 NF-κB 1157:1161 NF-κB 1157:1161 Activation of NF-κB, a key regulator in the cytokine production, was downregulated in the macrophages of the tumor tissues grown in Ogt-Tg/+ mice. 28536142 8 51 theme key 1166:1168 arg1 regulator 1170:1178 a key regulator 1164:1178 a key regulator in the cytokine production 1164:1205 Activation of NF-κB, a key regulator in the cytokine production, was downregulated in the macrophages of the tumor tissues grown in Ogt-Tg/+ mice. 28536142 9 52 theme MAPK 1717:1720 arg1 inhibition 1699:1708 the inhibition 1695:1708 the inhibition of p38 MAPK 1695:1720 These data reveal that elevated O-GlcNAcylation in the TME reduces the production of inflammatory cytokines and promotes cancer progression through downregulation of p38 MAPK activity and subsequent upregulation of the ERK1/2 signaling pathway.Implications: The reduced production of inflammatory cytokines by augmented O-GlcNAcylation in the TME, mainly macrophages, promotes tumor proliferation through the inhibition of p38 MAPK and suggests a possible cause of increased morbidity and mortality rates for various cancers in diabetic patients. 28536142 2 53 theme various 318:324 arg1 phenotypes 333:342 various cancer phenotypes 318:342 various cancer phenotypes 318:342 Recent studies indicate that increased O-GlcNAcylation is a general feature in cancer and contributes to various cancer phenotypes, including cell proliferation, survival, invasion, metastasis, and energy metabolism. 28536142 2 53 theme various 318:324 arg1 survival 375:382 survival 375:382 survival 375:382 Recent studies indicate that increased O-GlcNAcylation is a general feature in cancer and contributes to various cancer phenotypes, including cell proliferation, survival, invasion, metastasis, and energy metabolism. 28536142 2 53 theme various 318:324 arg1 invasion 385:392 invasion 385:392 invasion 385:392 Recent studies indicate that increased O-GlcNAcylation is a general feature in cancer and contributes to various cancer phenotypes, including cell proliferation, survival, invasion, metastasis, and energy metabolism. 28536142 2 53 theme various 318:324 arg1 metabolism 418:427 energy metabolism 411:427 energy metabolism 411:427 Recent studies indicate that increased O-GlcNAcylation is a general feature in cancer and contributes to various cancer phenotypes, including cell proliferation, survival, invasion, metastasis, and energy metabolism. 28536142 2 53 theme various 318:324 arg1 proliferation 360:372 cell proliferation 355:372 cell proliferation 355:372 Recent studies indicate that increased O-GlcNAcylation is a general feature in cancer and contributes to various cancer phenotypes, including cell proliferation, survival, invasion, metastasis, and energy metabolism. 28536142 2 53 theme various 318:324 arg1 metastasis 395:404 metastasis 395:404 metastasis 395:404 Recent studies indicate that increased O-GlcNAcylation is a general feature in cancer and contributes to various cancer phenotypes, including cell proliferation, survival, invasion, metastasis, and energy metabolism. 28536142 9 54 theme MAPK 1460:1463 arg1 activity 1465:1472 p38 MAPK activity 1456:1472 p38 MAPK activity 1456:1472 These data reveal that elevated O-GlcNAcylation in the TME reduces the production of inflammatory cytokines and promotes cancer progression through downregulation of p38 MAPK activity and subsequent upregulation of the ERK1/2 signaling pathway.Implications: The reduced production of inflammatory cytokines by augmented O-GlcNAcylation in the TME, mainly macrophages, promotes tumor proliferation through the inhibition of p38 MAPK and suggests a possible cause of increased morbidity and mortality rates for various cancers in diabetic patients. 28536142 9 55 theme p38 1456:1458 arg1 activity 1465:1472 p38 MAPK activity 1456:1472 p38 MAPK activity 1456:1472 These data reveal that elevated O-GlcNAcylation in the TME reduces the production of inflammatory cytokines and promotes cancer progression through downregulation of p38 MAPK activity and subsequent upregulation of the ERK1/2 signaling pathway.Implications: The reduced production of inflammatory cytokines by augmented O-GlcNAcylation in the TME, mainly macrophages, promotes tumor proliferation through the inhibition of p38 MAPK and suggests a possible cause of increased morbidity and mortality rates for various cancers in diabetic patients. 28536142 8 56 theme cytokine 1187:1194 arg1 production 1196:1205 the cytokine production 1183:1205 the cytokine production 1183:1205 Activation of NF-κB, a key regulator in the cytokine production, was downregulated in the macrophages of the tumor tissues grown in Ogt-Tg/+ mice. 28536142 6 57 theme activity 943:950 arg1 upregulation 956:967 upregulation 956:967 upregulation of the ERK1/2 signaling pathway 956:999 The tumors grown in Ogt-Tg/+ mice showed significant downregulation of p38 MAPK activity and upregulation of the ERK1/2 signaling pathway. 28536142 6 57 theme activity 943:950 arg1 downregulation 916:929 significant downregulation 904:929 significant downregulation of p38 MAPK activity 904:950 The tumors grown in Ogt-Tg/+ mice showed significant downregulation of p38 MAPK activity and upregulation of the ERK1/2 signaling pathway. 28536142 9 58 theme possible 1737:1744 arg1 cause 1746:1750 a possible cause 1735:1750 a possible cause of increased morbidity and mortality rates for various cancers in diabetic patients 1735:1834 These data reveal that elevated O-GlcNAcylation in the TME reduces the production of inflammatory cytokines and promotes cancer progression through downregulation of p38 MAPK activity and subsequent upregulation of the ERK1/2 signaling pathway.Implications: The reduced production of inflammatory cytokines by augmented O-GlcNAcylation in the TME, mainly macrophages, promotes tumor proliferation through the inhibition of p38 MAPK and suggests a possible cause of increased morbidity and mortality rates for various cancers in diabetic patients. 28536142 8 59 theme tumor 1252:1256 arg1 tissues 1258:1264 the tumor tissues 1248:1264 the tumor tissues grown in Ogt-Tg/+ mice 1248:1287 Activation of NF-κB, a key regulator in the cytokine production, was downregulated in the macrophages of the tumor tissues grown in Ogt-Tg/+ mice. 28536142 7 60 theme proinflammatory 1015:1029 arg1 production 1040:1049 proinflammatory cytokine production 1015:1049 proinflammatory cytokine production 1015:1049 In addition, proinflammatory cytokine production was significantly lower in the tumor tissues from Ogt-Tg/+ mice than in those from WT mice. 28536142 1 61 theme dynamic 116:122 arg1 O-GlcNAcylation 95:109 O-GlcNAcylation 95:109 O-GlcNAcylation 95:109 O-GlcNAcylation is a dynamic O-linked glycosylation event that plays a crucial role in regulating cellular signaling. 28536142 1 61 theme dynamic 116:122 arg1 event 147:151 a dynamic O-linked glycosylation event 114:151 a dynamic O-linked glycosylation event that plays a crucial role in regulating cellular signaling 114:210 O-GlcNAcylation is a dynamic O-linked glycosylation event that plays a crucial role in regulating cellular signaling. 28536142 6 62 theme p38 934:936 arg1 activity 943:950 p38 MAPK activity 934:950 p38 MAPK activity 934:950 The tumors grown in Ogt-Tg/+ mice showed significant downregulation of p38 MAPK activity and upregulation of the ERK1/2 signaling pathway. 28536142 7 63 theme cytokine 1031:1038 arg1 production 1040:1049 proinflammatory cytokine production 1015:1049 proinflammatory cytokine production 1015:1049 In addition, proinflammatory cytokine production was significantly lower in the tumor tissues from Ogt-Tg/+ mice than in those from WT mice. 28536142 1 64 theme glycosylation 133:145 arg1 O-GlcNAcylation 95:109 O-GlcNAcylation 95:109 O-GlcNAcylation 95:109 O-GlcNAcylation is a dynamic O-linked glycosylation event that plays a crucial role in regulating cellular signaling. 28536142 1 64 theme glycosylation 133:145 arg1 event 147:151 a dynamic O-linked glycosylation event 114:151 a dynamic O-linked glycosylation event that plays a crucial role in regulating cellular signaling 114:210 O-GlcNAcylation is a dynamic O-linked glycosylation event that plays a crucial role in regulating cellular signaling. 28536142 9 65 from O-GlcNAcylation 1610:1624 arg1 TME 1633:1635 the TME 1629:1635 the TME 1629:1635 These data reveal that elevated O-GlcNAcylation in the TME reduces the production of inflammatory cytokines and promotes cancer progression through downregulation of p38 MAPK activity and subsequent upregulation of the ERK1/2 signaling pathway.Implications: The reduced production of inflammatory cytokines by augmented O-GlcNAcylation in the TME, mainly macrophages, promotes tumor proliferation through the inhibition of p38 MAPK and suggests a possible cause of increased morbidity and mortality rates for various cancers in diabetic patients. 28536142 9 66 theme morbidity 1765:1773 arg1 rates 1789:1793 increased morbidity and mortality rates 1755:1793 increased morbidity and mortality rates for various cancers in diabetic patients 1755:1834 These data reveal that elevated O-GlcNAcylation in the TME reduces the production of inflammatory cytokines and promotes cancer progression through downregulation of p38 MAPK activity and subsequent upregulation of the ERK1/2 signaling pathway.Implications: The reduced production of inflammatory cytokines by augmented O-GlcNAcylation in the TME, mainly macrophages, promotes tumor proliferation through the inhibition of p38 MAPK and suggests a possible cause of increased morbidity and mortality rates for various cancers in diabetic patients. 28536142 8 67 theme Ogt-Tg/+ 1275:1282 arg1 mice 1284:1287 Ogt-Tg/+ mice 1275:1287 Ogt-Tg/+ mice 1275:1287 Activation of NF-κB, a key regulator in the cytokine production, was downregulated in the macrophages of the tumor tissues grown in Ogt-Tg/+ mice. 28536142 9 68 theme signaling 1516:1524 arg1 pathway.Implications 1526:1545 the ERK1/2 signaling pathway.Implications 1505:1545 the ERK1/2 signaling pathway.Implications 1505:1545 These data reveal that elevated O-GlcNAcylation in the TME reduces the production of inflammatory cytokines and promotes cancer progression through downregulation of p38 MAPK activity and subsequent upregulation of the ERK1/2 signaling pathway.Implications: The reduced production of inflammatory cytokines by augmented O-GlcNAcylation in the TME, mainly macrophages, promotes tumor proliferation through the inhibition of p38 MAPK and suggests a possible cause of increased morbidity and mortality rates for various cancers in diabetic patients. 28536142 9 68 theme signaling 1516:1524 arg1 macrophages 1645:1655 macrophages 1645:1655 macrophages 1645:1655 These data reveal that elevated O-GlcNAcylation in the TME reduces the production of inflammatory cytokines and promotes cancer progression through downregulation of p38 MAPK activity and subsequent upregulation of the ERK1/2 signaling pathway.Implications: The reduced production of inflammatory cytokines by augmented O-GlcNAcylation in the TME, mainly macrophages, promotes tumor proliferation through the inhibition of p38 MAPK and suggests a possible cause of increased morbidity and mortality rates for various cancers in diabetic patients. 28536142 9 69 theme mortality 1779:1787 arg1 rates 1789:1793 increased morbidity and mortality rates 1755:1793 increased morbidity and mortality rates for various cancers in diabetic patients 1755:1834 These data reveal that elevated O-GlcNAcylation in the TME reduces the production of inflammatory cytokines and promotes cancer progression through downregulation of p38 MAPK activity and subsequent upregulation of the ERK1/2 signaling pathway.Implications: The reduced production of inflammatory cytokines by augmented O-GlcNAcylation in the TME, mainly macrophages, promotes tumor proliferation through the inhibition of p38 MAPK and suggests a possible cause of increased morbidity and mortality rates for various cancers in diabetic patients. 28536142 0 70 theme MAPK 89:92 arg1 Inhibition 71:80 the Inhibition 67:80 the Inhibition of p38 MAPK 67:92 Augmented TME O-GlcNAcylation Promotes Tumor Proliferation through the Inhibition of p38 MAPK. 28536142 9 71 theme reduced 1552:1558 arg1 production 1560:1569 The reduced production 1548:1569 The reduced production of inflammatory cytokines by augmented O-GlcNAcylation in the TME 1548:1635 These data reveal that elevated O-GlcNAcylation in the TME reduces the production of inflammatory cytokines and promotes cancer progression through downregulation of p38 MAPK activity and subsequent upregulation of the ERK1/2 signaling pathway.Implications: The reduced production of inflammatory cytokines by augmented O-GlcNAcylation in the TME, mainly macrophages, promotes tumor proliferation through the inhibition of p38 MAPK and suggests a possible cause of increased morbidity and mortality rates for various cancers in diabetic patients. 28536142 6 72 theme signaling 983:991 arg1 pathway 993:999 the ERK1/2 signaling pathway 972:999 the ERK1/2 signaling pathway 972:999 The tumors grown in Ogt-Tg/+ mice showed significant downregulation of p38 MAPK activity and upregulation of the ERK1/2 signaling pathway. 28536142 9 73 dep reduces 1349:1355 arg1 promotes 1658:1665 promotes 1658:1665 promotes tumor proliferation through the inhibition of p38 MAPK 1658:1720 These data reveal that elevated O-GlcNAcylation in the TME reduces the production of inflammatory cytokines and promotes cancer progression through downregulation of p38 MAPK activity and subsequent upregulation of the ERK1/2 signaling pathway.Implications: The reduced production of inflammatory cytokines by augmented O-GlcNAcylation in the TME, mainly macrophages, promotes tumor proliferation through the inhibition of p38 MAPK and suggests a possible cause of increased morbidity and mortality rates for various cancers in diabetic patients. 28536142 9 74 from O-GlcNAcylation 1322:1336 arg1 TME 1345:1347 the TME 1341:1347 the TME 1341:1347 These data reveal that elevated O-GlcNAcylation in the TME reduces the production of inflammatory cytokines and promotes cancer progression through downregulation of p38 MAPK activity and subsequent upregulation of the ERK1/2 signaling pathway.Implications: The reduced production of inflammatory cytokines by augmented O-GlcNAcylation in the TME, mainly macrophages, promotes tumor proliferation through the inhibition of p38 MAPK and suggests a possible cause of increased morbidity and mortality rates for various cancers in diabetic patients. 28536142 9 75 theme activity 1465:1472 arg1 upregulation 1489:1500 subsequent upregulation 1478:1500 subsequent upregulation of the ERK1/2 signaling pathway.Implications: The reduced production of inflammatory cytokines by augmented O-GlcNAcylation in the TME, mainly macrophages 1478:1655 These data reveal that elevated O-GlcNAcylation in the TME reduces the production of inflammatory cytokines and promotes cancer progression through downregulation of p38 MAPK activity and subsequent upregulation of the ERK1/2 signaling pathway.Implications: The reduced production of inflammatory cytokines by augmented O-GlcNAcylation in the TME, mainly macrophages, promotes tumor proliferation through the inhibition of p38 MAPK and suggests a possible cause of increased morbidity and mortality rates for various cancers in diabetic patients. 28536142 9 75 theme activity 1465:1472 arg1 downregulation 1438:1451 downregulation 1438:1451 downregulation of p38 MAPK activity 1438:1472 These data reveal that elevated O-GlcNAcylation in the TME reduces the production of inflammatory cytokines and promotes cancer progression through downregulation of p38 MAPK activity and subsequent upregulation of the ERK1/2 signaling pathway.Implications: The reduced production of inflammatory cytokines by augmented O-GlcNAcylation in the TME, mainly macrophages, promotes tumor proliferation through the inhibition of p38 MAPK and suggests a possible cause of increased morbidity and mortality rates for various cancers in diabetic patients. 28536142 9 76 theme diabetic 1818:1825 arg1 patients 1827:1834 diabetic patients 1818:1834 diabetic patients 1818:1834 These data reveal that elevated O-GlcNAcylation in the TME reduces the production of inflammatory cytokines and promotes cancer progression through downregulation of p38 MAPK activity and subsequent upregulation of the ERK1/2 signaling pathway.Implications: The reduced production of inflammatory cytokines by augmented O-GlcNAcylation in the TME, mainly macrophages, promotes tumor proliferation through the inhibition of p38 MAPK and suggests a possible cause of increased morbidity and mortality rates for various cancers in diabetic patients. 28536142 0 77 theme TME 10:12 arg1 O-GlcNAcylation 14:28 Augmented TME O-GlcNAcylation 0:28 Augmented TME O-GlcNAcylation 0:28 Augmented TME O-GlcNAcylation Promotes Tumor Proliferation through the Inhibition of p38 MAPK. 28536142 9 78 theme cytokines 1587:1595 arg1 production 1560:1569 The reduced production 1548:1569 The reduced production of inflammatory cytokines by augmented O-GlcNAcylation in the TME 1548:1635 These data reveal that elevated O-GlcNAcylation in the TME reduces the production of inflammatory cytokines and promotes cancer progression through downregulation of p38 MAPK activity and subsequent upregulation of the ERK1/2 signaling pathway.Implications: The reduced production of inflammatory cytokines by augmented O-GlcNAcylation in the TME, mainly macrophages, promotes tumor proliferation through the inhibition of p38 MAPK and suggests a possible cause of increased morbidity and mortality rates for various cancers in diabetic patients. 28536142 9 79 theme elevated 1313:1320 arg1 O-GlcNAcylation 1322:1336 elevated O-GlcNAcylation 1313:1336 elevated O-GlcNAcylation in the TME 1313:1347 These data reveal that elevated O-GlcNAcylation in the TME reduces the production of inflammatory cytokines and promotes cancer progression through downregulation of p38 MAPK activity and subsequent upregulation of the ERK1/2 signaling pathway.Implications: The reduced production of inflammatory cytokines by augmented O-GlcNAcylation in the TME, mainly macrophages, promotes tumor proliferation through the inhibition of p38 MAPK and suggests a possible cause of increased morbidity and mortality rates for various cancers in diabetic patients. 28536142 9 80 theme augmented 1600:1608 arg1 O-GlcNAcylation 1610:1624 augmented O-GlcNAcylation 1600:1624 augmented O-GlcNAcylation in the TME 1600:1635 These data reveal that elevated O-GlcNAcylation in the TME reduces the production of inflammatory cytokines and promotes cancer progression through downregulation of p38 MAPK activity and subsequent upregulation of the ERK1/2 signaling pathway.Implications: The reduced production of inflammatory cytokines by augmented O-GlcNAcylation in the TME, mainly macrophages, promotes tumor proliferation through the inhibition of p38 MAPK and suggests a possible cause of increased morbidity and mortality rates for various cancers in diabetic patients. 28536142 9 81 dep pathway.Implications 1526:1545 arg1 production 1560:1569 The reduced production 1548:1569 The reduced production of inflammatory cytokines by augmented O-GlcNAcylation in the TME 1548:1635 These data reveal that elevated O-GlcNAcylation in the TME reduces the production of inflammatory cytokines and promotes cancer progression through downregulation of p38 MAPK activity and subsequent upregulation of the ERK1/2 signaling pathway.Implications: The reduced production of inflammatory cytokines by augmented O-GlcNAcylation in the TME, mainly macrophages, promotes tumor proliferation through the inhibition of p38 MAPK and suggests a possible cause of increased morbidity and mortality rates for various cancers in diabetic patients. 28536142 3 82 theme tumor 474:478 arg1 TME 498:500 TME 498:500 TME 498:500 However, the role of O-GlcNAcylation in the tumor microenvironment (TME) is not fully elucidated. 28536142 3 82 theme tumor 474:478 arg1 microenvironment 480:495 the tumor microenvironment 470:495 the tumor microenvironment (TME) 470:501 However, the role of O-GlcNAcylation in the tumor microenvironment (TME) is not fully elucidated. 28536142 2 83 theme energy 411:416 arg1 metabolism 418:427 energy metabolism 411:427 energy metabolism 411:427 Recent studies indicate that increased O-GlcNAcylation is a general feature in cancer and contributes to various cancer phenotypes, including cell proliferation, survival, invasion, metastasis, and energy metabolism. 28536142 7 84 theme WT 1134:1135 arg1 mice 1137:1140 WT mice 1134:1140 WT mice 1134:1140 In addition, proinflammatory cytokine production was significantly lower in the tumor tissues from Ogt-Tg/+ mice than in those from WT mice. 28536142 9 85 from cancers 1807:1813 arg1 patients 1827:1834 diabetic patients 1818:1834 diabetic patients 1818:1834 These data reveal that elevated O-GlcNAcylation in the TME reduces the production of inflammatory cytokines and promotes cancer progression through downregulation of p38 MAPK activity and subsequent upregulation of the ERK1/2 signaling pathway.Implications: The reduced production of inflammatory cytokines by augmented O-GlcNAcylation in the TME, mainly macrophages, promotes tumor proliferation through the inhibition of p38 MAPK and suggests a possible cause of increased morbidity and mortality rates for various cancers in diabetic patients. 28536142 4 86 theme B16 534:536 arg1 cells 547:551 B16 melanoma cells 534:551 B16 melanoma cells 534:551 Here, B16 melanoma cells were subcutaneously transplanted into O-GlcNAc transferase transgenic (Ogt-Tg) mice exhibiting elevated O-GlcNAcylation to examine the effect of O-GlcNAcylation in the TME on tumor progression. 28536142 2 87 theme cell 355:358 arg1 proliferation 360:372 cell proliferation 355:372 cell proliferation 355:372 Recent studies indicate that increased O-GlcNAcylation is a general feature in cancer and contributes to various cancer phenotypes, including cell proliferation, survival, invasion, metastasis, and energy metabolism. 28536142 1 88 link O-linked 124:131 arg1 O-GlcNAcylation 95:109 O-GlcNAcylation 95:109 O-GlcNAcylation 95:109 O-GlcNAcylation is a dynamic O-linked glycosylation event that plays a crucial role in regulating cellular signaling. 28536142 1 88 link O-linked 124:131 arg1 event 147:151 a dynamic O-linked glycosylation event 114:151 a dynamic O-linked glycosylation event that plays a crucial role in regulating cellular signaling 114:210 O-GlcNAcylation is a dynamic O-linked glycosylation event that plays a crucial role in regulating cellular signaling. 28536142 4 89 theme elevated 648:655 arg1 O-GlcNAcylation 657:671 elevated O-GlcNAcylation 648:671 elevated O-GlcNAcylation 648:671 Here, B16 melanoma cells were subcutaneously transplanted into O-GlcNAc transferase transgenic (Ogt-Tg) mice exhibiting elevated O-GlcNAcylation to examine the effect of O-GlcNAcylation in the TME on tumor progression. 28536142 5 90 dep wild-type 842:850 arg1 WT 853:854 WT 853:854 WT 853:854 In this model system, B16 tumor growth was significantly higher in Ogt-Tg/+ mice compared with wild-type (WT) mice. 28536142 3 91 from role 443:446 arg1 TME 498:500 TME 498:500 TME 498:500 However, the role of O-GlcNAcylation in the tumor microenvironment (TME) is not fully elucidated. 28536142 3 91 from role 443:446 arg1 microenvironment 480:495 the tumor microenvironment 470:495 the tumor microenvironment (TME) 470:501 However, the role of O-GlcNAcylation in the tumor microenvironment (TME) is not fully elucidated. 28536142 9 92 theme cytokines 1388:1396 arg1 production 1361:1370 the production 1357:1370 the production of inflammatory cytokines 1357:1396 These data reveal that elevated O-GlcNAcylation in the TME reduces the production of inflammatory cytokines and promotes cancer progression through downregulation of p38 MAPK activity and subsequent upregulation of the ERK1/2 signaling pathway.Implications: The reduced production of inflammatory cytokines by augmented O-GlcNAcylation in the TME, mainly macrophages, promotes tumor proliferation through the inhibition of p38 MAPK and suggests a possible cause of increased morbidity and mortality rates for various cancers in diabetic patients. 28264048 2 0 link O-linked 596:603 arg1 oligosaccharides 605:620 O-linked oligosaccharides 596:620 O-linked oligosaccharides 596:620 T. forsythia is a unique Gram-negative organism endowed with an elaborate protein O-glycosylation system that allows the bacterium to express a glycosylated surface (S)-layer comprising two high molecular weight glycoproteins modified with O-linked oligosaccharides. 28264048 6 1 theme Ca2+-dependent 1302:1315 arg1 binding 1317:1323 a specific Ca2+-dependent binding 1291:1323 a specific Ca2+-dependent binding of Mincle to T. forsythia S-layer 1291:1357 Binding studies using recombinant Mincle-Fc fusion protein indicated a specific Ca2+-dependent binding of Mincle to T. forsythia S-layer. 28264048 4 2 from variety 967:973 arg1 pathogens 1029:1037 fungal and bacterial pathogens 1008:1037 pathogens 1029:1037 The macrophage-inducible C-type lectin receptor (Mincle) is an FcRγ-coupled pathogen recognition receptor that recognizes a wide variety of sugar containing ligands from fungal and bacterial pathogens. 28264048 7 3 theme secretion 1547:1555 arg1 induction 1493:1501 the induction 1489:1501 the induction of both pro- and anti-inflammatory cytokine secretion in macrophages stimulated with T. forsythia 1489:1599 Subsequent experiments with Mincle-expressing and Mincle-knockdown macrophages revealed a role for Mincle/S-layer interaction in the induction of both pro- and anti-inflammatory cytokine secretion in macrophages stimulated with T. forsythia as well as its S-layer. 28264048 3 4 theme presenting 719:728 arg1 cells 730:734 antigen presenting cells 711:734 antigen presenting cells 711:734 The T. forsythia S-layer has been implicated in the modulation of cytokine responses of antigen presenting cells, such as macrophages, that play a significant role during inflammation associated with periodontitis. 28264048 7 5 theme anti-inflammatory 1520:1536 arg1 secretion 1547:1555 both pro- and anti-inflammatory cytokine secretion 1506:1555 both pro- and anti-inflammatory cytokine secretion 1506:1555 Subsequent experiments with Mincle-expressing and Mincle-knockdown macrophages revealed a role for Mincle/S-layer interaction in the induction of both pro- and anti-inflammatory cytokine secretion in macrophages stimulated with T. forsythia as well as its S-layer. 28264048 4 6 theme macrophage-inducible 842:861 arg1 receptor 935:942 an FcRγ-coupled pathogen recognition receptor 898:942 an FcRγ-coupled pathogen recognition receptor that recognizes a wide variety of sugar containing ligands from fungal and bacterial pathogens 898:1037 The macrophage-inducible C-type lectin receptor (Mincle) is an FcRγ-coupled pathogen recognition receptor that recognizes a wide variety of sugar containing ligands from fungal and bacterial pathogens. 28264048 4 6 theme macrophage-inducible 842:861 arg1 Mincle 887:892 Mincle 887:892 Mincle 887:892 The macrophage-inducible C-type lectin receptor (Mincle) is an FcRγ-coupled pathogen recognition receptor that recognizes a wide variety of sugar containing ligands from fungal and bacterial pathogens. 28264048 4 6 theme macrophage-inducible 842:861 arg1 receptor 877:884 The macrophage-inducible C-type lectin receptor 838:884 The macrophage-inducible C-type lectin receptor (Mincle) 838:893 The macrophage-inducible C-type lectin receptor (Mincle) is an FcRγ-coupled pathogen recognition receptor that recognizes a wide variety of sugar containing ligands from fungal and bacterial pathogens. 28264048 7 7 theme pro- 1511:1514 arg1 secretion 1547:1555 both pro- and anti-inflammatory cytokine secretion 1506:1555 both pro- and anti-inflammatory cytokine secretion 1506:1555 Subsequent experiments with Mincle-expressing and Mincle-knockdown macrophages revealed a role for Mincle/S-layer interaction in the induction of both pro- and anti-inflammatory cytokine secretion in macrophages stimulated with T. forsythia as well as its S-layer. 28264048 4 8 theme lectin 870:875 arg1 receptor 935:942 an FcRγ-coupled pathogen recognition receptor 898:942 an FcRγ-coupled pathogen recognition receptor that recognizes a wide variety of sugar containing ligands from fungal and bacterial pathogens 898:1037 The macrophage-inducible C-type lectin receptor (Mincle) is an FcRγ-coupled pathogen recognition receptor that recognizes a wide variety of sugar containing ligands from fungal and bacterial pathogens. 28264048 4 8 theme lectin 870:875 arg1 Mincle 887:892 Mincle 887:892 Mincle 887:892 The macrophage-inducible C-type lectin receptor (Mincle) is an FcRγ-coupled pathogen recognition receptor that recognizes a wide variety of sugar containing ligands from fungal and bacterial pathogens. 28264048 4 8 theme lectin 870:875 arg1 receptor 877:884 The macrophage-inducible C-type lectin receptor 838:884 The macrophage-inducible C-type lectin receptor (Mincle) 838:893 The macrophage-inducible C-type lectin receptor (Mincle) is an FcRγ-coupled pathogen recognition receptor that recognizes a wide variety of sugar containing ligands from fungal and bacterial pathogens. 28264048 7 9 theme Mincle/S-layer 1459:1472 arg1 interaction 1474:1484 Mincle/S-layer interaction 1459:1484 Mincle/S-layer interaction 1459:1484 Subsequent experiments with Mincle-expressing and Mincle-knockdown macrophages revealed a role for Mincle/S-layer interaction in the induction of both pro- and anti-inflammatory cytokine secretion in macrophages stimulated with T. forsythia as well as its S-layer. 28264048 6 10 theme Mincle-Fc 1256:1264 arg1 protein 1273:1279 recombinant Mincle-Fc fusion protein 1244:1279 recombinant Mincle-Fc fusion protein 1244:1279 Binding studies using recombinant Mincle-Fc fusion protein indicated a specific Ca2+-dependent binding of Mincle to T. forsythia S-layer. 28264048 0 11 theme periodontal 93:103 arg1 forsythia 125:133 the periodontal pathogen Tannerella forsythia 89:133 the periodontal pathogen Tannerella forsythia 89:133 Macrophage inducible C-type lectin (Mincle) recognizes glycosylated surface (S)-layer of the periodontal pathogen Tannerella forsythia. 28264048 8 12 theme critical 1807:1814 arg1 role 1816:1819 a critical role 1805:1819 a critical role 1805:1819 Together, these studies revealed Mincle as an important macrophage receptor involved in the modulation of cytokine responses of macrophages against T. forsythia, and thus may play a critical role in orchestrating the host immune response against the bacterium. 28264048 2 13 theme S 522:522 arg1 -layer 524:529 a glycosylated surface (S)-layer 498:529 a glycosylated surface (S)-layer comprising two high molecular weight glycoproteins modified with O-linked oligosaccharides 498:620 T. forsythia is a unique Gram-negative organism endowed with an elaborate protein O-glycosylation system that allows the bacterium to express a glycosylated surface (S)-layer comprising two high molecular weight glycoproteins modified with O-linked oligosaccharides. 28264048 6 14 theme recombinant 1244:1254 arg1 protein 1273:1279 recombinant Mincle-Fc fusion protein 1244:1279 recombinant Mincle-Fc fusion protein 1244:1279 Binding studies using recombinant Mincle-Fc fusion protein indicated a specific Ca2+-dependent binding of Mincle to T. forsythia S-layer. 28264048 3 15 theme play 763:766 arg1 responses 698:706 cytokine responses 689:706 cytokine responses of antigen presenting cells, such as macrophages, that play a significant role during inflammation associated with periodontitis 689:835 The T. forsythia S-layer has been implicated in the modulation of cytokine responses of antigen presenting cells, such as macrophages, that play a significant role during inflammation associated with periodontitis. 28264048 0 16 theme Tannerella 114:123 arg1 forsythia 125:133 the periodontal pathogen Tannerella forsythia 89:133 the periodontal pathogen Tannerella forsythia 89:133 Macrophage inducible C-type lectin (Mincle) recognizes glycosylated surface (S)-layer of the periodontal pathogen Tannerella forsythia. 28264048 2 17 gly glycoproteins 568:580 arg1 glycoproteins 568:580 two high molecular weight glycoproteins 542:580 two high molecular weight glycoproteins modified with O-linked oligosaccharides 542:620 T. forsythia is a unique Gram-negative organism endowed with an elaborate protein O-glycosylation system that allows the bacterium to express a glycosylated surface (S)-layer comprising two high molecular weight glycoproteins modified with O-linked oligosaccharides. 28264048 2 18 theme molecular 551:559 arg1 glycoproteins 568:580 two high molecular weight glycoproteins 542:580 two high molecular weight glycoproteins modified with O-linked oligosaccharides 542:620 T. forsythia is a unique Gram-negative organism endowed with an elaborate protein O-glycosylation system that allows the bacterium to express a glycosylated surface (S)-layer comprising two high molecular weight glycoproteins modified with O-linked oligosaccharides. 28264048 7 19 theme Mincle-knockdown 1410:1425 arg1 macrophages 1427:1437 Mincle-expressing and Mincle-knockdown macrophages 1388:1437 Mincle-expressing and Mincle-knockdown macrophages 1388:1437 Subsequent experiments with Mincle-expressing and Mincle-knockdown macrophages revealed a role for Mincle/S-layer interaction in the induction of both pro- and anti-inflammatory cytokine secretion in macrophages stimulated with T. forsythia as well as its S-layer. 28264048 7 20 from role 1450:1453 arg1 induction 1493:1501 the induction 1489:1501 the induction of both pro- and anti-inflammatory cytokine secretion in macrophages stimulated with T. forsythia 1489:1599 Subsequent experiments with Mincle-expressing and Mincle-knockdown macrophages revealed a role for Mincle/S-layer interaction in the induction of both pro- and anti-inflammatory cytokine secretion in macrophages stimulated with T. forsythia as well as its S-layer. 28264048 4 21 theme pathogen 914:921 arg1 receptor 935:942 an FcRγ-coupled pathogen recognition receptor 898:942 an FcRγ-coupled pathogen recognition receptor that recognizes a wide variety of sugar containing ligands from fungal and bacterial pathogens 898:1037 The macrophage-inducible C-type lectin receptor (Mincle) is an FcRγ-coupled pathogen recognition receptor that recognizes a wide variety of sugar containing ligands from fungal and bacterial pathogens. 28264048 4 21 theme pathogen 914:921 arg1 receptor 877:884 The macrophage-inducible C-type lectin receptor 838:884 The macrophage-inducible C-type lectin receptor (Mincle) 838:893 The macrophage-inducible C-type lectin receptor (Mincle) is an FcRγ-coupled pathogen recognition receptor that recognizes a wide variety of sugar containing ligands from fungal and bacterial pathogens. 28264048 7 22 theme Mincle-expressing 1388:1404 arg1 macrophages 1427:1437 Mincle-expressing and Mincle-knockdown macrophages 1388:1437 Mincle-expressing and Mincle-knockdown macrophages 1388:1437 Subsequent experiments with Mincle-expressing and Mincle-knockdown macrophages revealed a role for Mincle/S-layer interaction in the induction of both pro- and anti-inflammatory cytokine secretion in macrophages stimulated with T. forsythia as well as its S-layer. 28264048 8 23 theme immune 1847:1852 arg1 response 1854:1861 the host immune response 1838:1861 the host immune response 1838:1861 Together, these studies revealed Mincle as an important macrophage receptor involved in the modulation of cytokine responses of macrophages against T. forsythia, and thus may play a critical role in orchestrating the host immune response against the bacterium. 28264048 4 24 theme containing 984:993 arg1 ligands 995:1001 sugar containing ligands 978:1001 sugar containing ligands from fungal and bacterial pathogens 978:1037 The macrophage-inducible C-type lectin receptor (Mincle) is an FcRγ-coupled pathogen recognition receptor that recognizes a wide variety of sugar containing ligands from fungal and bacterial pathogens. 28264048 3 25 theme significant 770:780 arg1 role 782:785 a significant role 768:785 a significant role 768:785 The T. forsythia S-layer has been implicated in the modulation of cytokine responses of antigen presenting cells, such as macrophages, that play a significant role during inflammation associated with periodontitis. 28264048 0 26 theme glycosylated 55:66 arg1 -layer 79:84 glycosylated surface (S)-layer 55:84 glycosylated surface (S)-layer of the periodontal pathogen Tannerella forsythia 55:133 Macrophage inducible C-type lectin (Mincle) recognizes glycosylated surface (S)-layer of the periodontal pathogen Tannerella forsythia. 28264048 1 27 theme supporting 307:316 arg1 tissues 318:324 the gum and tooth supporting tissues 289:324 the gum and tooth supporting tissues 289:324 The oral pathogen Tannerella forsythia is implicated in the development of periodontitis, a common inflammatory disease that leads to the destruction of the gum and tooth supporting tissues, often leading to tooth loss. 28264048 1 28 theme pathogen 145:152 arg1 forsythia 165:173 The oral pathogen Tannerella forsythia 136:173 The oral pathogen Tannerella forsythia 136:173 The oral pathogen Tannerella forsythia is implicated in the development of periodontitis, a common inflammatory disease that leads to the destruction of the gum and tooth supporting tissues, often leading to tooth loss. 28264048 7 29 from induction 1493:1501 arg1 macrophages 1560:1570 macrophages 1560:1570 macrophages stimulated with T. forsythia 1560:1599 Subsequent experiments with Mincle-expressing and Mincle-knockdown macrophages revealed a role for Mincle/S-layer interaction in the induction of both pro- and anti-inflammatory cytokine secretion in macrophages stimulated with T. forsythia as well as its S-layer. 28264048 2 30 theme surface 513:519 arg1 -layer 524:529 a glycosylated surface (S)-layer 498:529 a glycosylated surface (S)-layer comprising two high molecular weight glycoproteins modified with O-linked oligosaccharides 498:620 T. forsythia is a unique Gram-negative organism endowed with an elaborate protein O-glycosylation system that allows the bacterium to express a glycosylated surface (S)-layer comprising two high molecular weight glycoproteins modified with O-linked oligosaccharides. 28264048 1 31 theme tooth 344:348 arg1 loss 350:353 tooth loss 344:353 tooth loss 344:353 The oral pathogen Tannerella forsythia is implicated in the development of periodontitis, a common inflammatory disease that leads to the destruction of the gum and tooth supporting tissues, often leading to tooth loss. 28264048 7 32 theme Subsequent 1360:1369 arg1 experiments 1371:1381 Subsequent experiments 1360:1381 Subsequent experiments with Mincle-expressing and Mincle-knockdown macrophages 1360:1437 Subsequent experiments with Mincle-expressing and Mincle-knockdown macrophages revealed a role for Mincle/S-layer interaction in the induction of both pro- and anti-inflammatory cytokine secretion in macrophages stimulated with T. forsythia as well as its S-layer. 28264048 7 33 with experiments 1371:1381 arg1 macrophages 1427:1437 Mincle-expressing and Mincle-knockdown macrophages 1388:1437 Mincle-expressing and Mincle-knockdown macrophages 1388:1437 Subsequent experiments with Mincle-expressing and Mincle-knockdown macrophages revealed a role for Mincle/S-layer interaction in the induction of both pro- and anti-inflammatory cytokine secretion in macrophages stimulated with T. forsythia as well as its S-layer. 28264048 0 34 theme Macrophage 0:9 arg1 Mincle 36:41 Mincle 36:41 Mincle 36:41 Macrophage inducible C-type lectin (Mincle) recognizes glycosylated surface (S)-layer of the periodontal pathogen Tannerella forsythia. 28264048 0 34 theme Macrophage 0:9 arg1 lectin 28:33 Macrophage inducible C-type lectin 0:33 Macrophage inducible C-type lectin (Mincle) 0:42 Macrophage inducible C-type lectin (Mincle) recognizes glycosylated surface (S)-layer of the periodontal pathogen Tannerella forsythia. 28264048 5 35 theme cytokine 1166:1173 arg1 response 1175:1182 cytokine response 1166:1182 cytokine response of macrophages against the bacterium 1166:1219 In this study, we aimed to determine if Mincle might be involved in the recognition of T. forsythia S-layer and modulation of cytokine response of macrophages against the bacterium. 28264048 0 36 theme C-type 21:26 arg1 Mincle 36:41 Mincle 36:41 Mincle 36:41 Macrophage inducible C-type lectin (Mincle) recognizes glycosylated surface (S)-layer of the periodontal pathogen Tannerella forsythia. 28264048 0 36 theme C-type 21:26 arg1 lectin 28:33 Macrophage inducible C-type lectin 0:33 Macrophage inducible C-type lectin (Mincle) 0:42 Macrophage inducible C-type lectin (Mincle) recognizes glycosylated surface (S)-layer of the periodontal pathogen Tannerella forsythia. 28264048 2 37 theme unique 374:379 arg1 forsythia 359:367 T. forsythia 356:367 T. forsythia 356:367 T. forsythia is a unique Gram-negative organism endowed with an elaborate protein O-glycosylation system that allows the bacterium to express a glycosylated surface (S)-layer comprising two high molecular weight glycoproteins modified with O-linked oligosaccharides. 28264048 2 37 theme unique 374:379 arg1 organism 395:402 a unique Gram-negative organism 372:402 a unique Gram-negative organism endowed with an elaborate protein O-glycosylation system that allows the bacterium to express a glycosylated surface (S)-layer comprising two high molecular weight glycoproteins modified with O-linked oligosaccharides 372:620 T. forsythia is a unique Gram-negative organism endowed with an elaborate protein O-glycosylation system that allows the bacterium to express a glycosylated surface (S)-layer comprising two high molecular weight glycoproteins modified with O-linked oligosaccharides. 28264048 4 38 from pathogens 1029:1037 arg1 variety 967:973 a wide variety 960:973 a wide variety of sugar containing ligands from fungal and bacterial pathogens 960:1037 The macrophage-inducible C-type lectin receptor (Mincle) is an FcRγ-coupled pathogen recognition receptor that recognizes a wide variety of sugar containing ligands from fungal and bacterial pathogens. 28264048 4 38 from pathogens 1029:1037 arg1 ligands 995:1001 sugar containing ligands 978:1001 sugar containing ligands from fungal and bacterial pathogens 978:1037 The macrophage-inducible C-type lectin receptor (Mincle) is an FcRγ-coupled pathogen recognition receptor that recognizes a wide variety of sugar containing ligands from fungal and bacterial pathogens. 28264048 2 39 theme O-glycosylation 438:452 arg1 system 454:459 an elaborate protein O-glycosylation system 417:459 an elaborate protein O-glycosylation system that allows the bacterium to express a glycosylated surface (S)-layer comprising two high molecular weight glycoproteins modified with O-linked oligosaccharides 417:620 T. forsythia is a unique Gram-negative organism endowed with an elaborate protein O-glycosylation system that allows the bacterium to express a glycosylated surface (S)-layer comprising two high molecular weight glycoproteins modified with O-linked oligosaccharides. 28264048 5 40 theme S-layer 1140:1146 arg1 modulation 1152:1161 modulation 1152:1161 modulation of cytokine response of macrophages against the bacterium 1152:1219 In this study, we aimed to determine if Mincle might be involved in the recognition of T. forsythia S-layer and modulation of cytokine response of macrophages against the bacterium. 28264048 5 40 theme S-layer 1140:1146 arg1 recognition 1112:1122 the recognition 1108:1122 the recognition of T. forsythia S-layer 1108:1146 In this study, we aimed to determine if Mincle might be involved in the recognition of T. forsythia S-layer and modulation of cytokine response of macrophages against the bacterium. 28264048 3 41 theme forsythia 630:638 arg1 S-layer 640:646 The T. forsythia S-layer 623:646 The T. forsythia S-layer 623:646 The T. forsythia S-layer has been implicated in the modulation of cytokine responses of antigen presenting cells, such as macrophages, that play a significant role during inflammation associated with periodontitis. 28264048 1 42 theme periodontitis 211:223 arg1 development 196:206 the development 192:206 the development of periodontitis, a common inflammatory disease that leads to the destruction of the gum and tooth supporting tissues, often leading to tooth loss 192:353 The oral pathogen Tannerella forsythia is implicated in the development of periodontitis, a common inflammatory disease that leads to the destruction of the gum and tooth supporting tissues, often leading to tooth loss. 28264048 8 43 theme cytokine 1731:1738 arg1 responses 1740:1748 cytokine responses 1731:1748 cytokine responses of macrophages against T. forsythia 1731:1784 Together, these studies revealed Mincle as an important macrophage receptor involved in the modulation of cytokine responses of macrophages against T. forsythia, and thus may play a critical role in orchestrating the host immune response against the bacterium. 28264048 8 44 theme important 1671:1679 arg1 receptor 1692:1699 an important macrophage receptor 1668:1699 an important macrophage receptor involved in the modulation of cytokine responses of macrophages against T. forsythia 1668:1784 Together, these studies revealed Mincle as an important macrophage receptor involved in the modulation of cytokine responses of macrophages against T. forsythia, and thus may play a critical role in orchestrating the host immune response against the bacterium. 28264048 8 44 theme important 1671:1679 arg1 Mincle 1658:1663 Mincle 1658:1663 Mincle 1658:1663 Together, these studies revealed Mincle as an important macrophage receptor involved in the modulation of cytokine responses of macrophages against T. forsythia, and thus may play a critical role in orchestrating the host immune response against the bacterium. 28264048 3 45 theme responses 698:706 arg1 modulation 675:684 the modulation 671:684 the modulation of cytokine responses of antigen presenting cells, such as macrophages, that play a significant role during inflammation associated with periodontitis 671:835 The T. forsythia S-layer has been implicated in the modulation of cytokine responses of antigen presenting cells, such as macrophages, that play a significant role during inflammation associated with periodontitis. 28264048 1 46 theme inflammatory 235:246 arg1 disease 248:254 a common inflammatory disease 226:254 a common inflammatory disease that leads to the destruction of the gum and tooth supporting tissues, often leading to tooth loss 226:353 The oral pathogen Tannerella forsythia is implicated in the development of periodontitis, a common inflammatory disease that leads to the destruction of the gum and tooth supporting tissues, often leading to tooth loss. 28264048 1 46 theme inflammatory 235:246 arg1 periodontitis 211:223 periodontitis 211:223 periodontitis 211:223 The oral pathogen Tannerella forsythia is implicated in the development of periodontitis, a common inflammatory disease that leads to the destruction of the gum and tooth supporting tissues, often leading to tooth loss. 28264048 3 47 dep such 737:740 arg1 as 742:743 as 742:743 as 742:743 The T. forsythia S-layer has been implicated in the modulation of cytokine responses of antigen presenting cells, such as macrophages, that play a significant role during inflammation associated with periodontitis. 28264048 7 48 theme cytokine 1538:1545 arg1 secretion 1547:1555 both pro- and anti-inflammatory cytokine secretion 1506:1555 both pro- and anti-inflammatory cytokine secretion 1506:1555 Subsequent experiments with Mincle-expressing and Mincle-knockdown macrophages revealed a role for Mincle/S-layer interaction in the induction of both pro- and anti-inflammatory cytokine secretion in macrophages stimulated with T. forsythia as well as its S-layer. 28264048 6 49 theme specific 1293:1300 arg1 binding 1317:1323 a specific Ca2+-dependent binding 1291:1323 a specific Ca2+-dependent binding of Mincle to T. forsythia S-layer 1291:1357 Binding studies using recombinant Mincle-Fc fusion protein indicated a specific Ca2+-dependent binding of Mincle to T. forsythia S-layer. 28264048 2 50 theme weight 561:566 arg1 glycoproteins 568:580 two high molecular weight glycoproteins 542:580 two high molecular weight glycoproteins modified with O-linked oligosaccharides 542:620 T. forsythia is a unique Gram-negative organism endowed with an elaborate protein O-glycosylation system that allows the bacterium to express a glycosylated surface (S)-layer comprising two high molecular weight glycoproteins modified with O-linked oligosaccharides. 28264048 3 51 theme cells 730:734 arg1 responses 698:706 cytokine responses 689:706 cytokine responses of antigen presenting cells, such as macrophages, that play a significant role during inflammation associated with periodontitis 689:835 The T. forsythia S-layer has been implicated in the modulation of cytokine responses of antigen presenting cells, such as macrophages, that play a significant role during inflammation associated with periodontitis. 28264048 1 52 theme Tannerella 154:163 arg1 forsythia 165:173 The oral pathogen Tannerella forsythia 136:173 The oral pathogen Tannerella forsythia 136:173 The oral pathogen Tannerella forsythia is implicated in the development of periodontitis, a common inflammatory disease that leads to the destruction of the gum and tooth supporting tissues, often leading to tooth loss. 28264048 2 53 theme protein 430:436 arg1 O-glycosylation 438:452 elaborate protein O-glycosylation 420:452 an elaborate protein O-glycosylation system that allows the bacterium to express a glycosylated surface (S)-layer comprising two high molecular weight glycoproteins modified with O-linked oligosaccharides 417:620 T. forsythia is a unique Gram-negative organism endowed with an elaborate protein O-glycosylation system that allows the bacterium to express a glycosylated surface (S)-layer comprising two high molecular weight glycoproteins modified with O-linked oligosaccharides. 28264048 3 54 theme antigen 711:717 arg1 cells 730:734 antigen presenting cells 711:734 antigen presenting cells 711:734 The T. forsythia S-layer has been implicated in the modulation of cytokine responses of antigen presenting cells, such as macrophages, that play a significant role during inflammation associated with periodontitis. 28264048 6 55 theme fusion 1266:1271 arg1 protein 1273:1279 recombinant Mincle-Fc fusion protein 1244:1279 recombinant Mincle-Fc fusion protein 1244:1279 Binding studies using recombinant Mincle-Fc fusion protein indicated a specific Ca2+-dependent binding of Mincle to T. forsythia S-layer. 28264048 2 56 theme O-linked 596:603 arg1 oligosaccharides 605:620 O-linked oligosaccharides 596:620 O-linked oligosaccharides 596:620 T. forsythia is a unique Gram-negative organism endowed with an elaborate protein O-glycosylation system that allows the bacterium to express a glycosylated surface (S)-layer comprising two high molecular weight glycoproteins modified with O-linked oligosaccharides. 28264048 3 57 theme macrophages 745:755 arg1 responses 698:706 cytokine responses 689:706 cytokine responses of antigen presenting cells, such as macrophages, that play a significant role during inflammation associated with periodontitis 689:835 The T. forsythia S-layer has been implicated in the modulation of cytokine responses of antigen presenting cells, such as macrophages, that play a significant role during inflammation associated with periodontitis. 28264048 0 58 theme pathogen 105:112 arg1 forsythia 125:133 the periodontal pathogen Tannerella forsythia 89:133 the periodontal pathogen Tannerella forsythia 89:133 Macrophage inducible C-type lectin (Mincle) recognizes glycosylated surface (S)-layer of the periodontal pathogen Tannerella forsythia. 28264048 4 59 theme recognition 923:933 arg1 receptor 935:942 an FcRγ-coupled pathogen recognition receptor 898:942 an FcRγ-coupled pathogen recognition receptor that recognizes a wide variety of sugar containing ligands from fungal and bacterial pathogens 898:1037 The macrophage-inducible C-type lectin receptor (Mincle) is an FcRγ-coupled pathogen recognition receptor that recognizes a wide variety of sugar containing ligands from fungal and bacterial pathogens. 28264048 4 59 theme recognition 923:933 arg1 receptor 877:884 The macrophage-inducible C-type lectin receptor 838:884 The macrophage-inducible C-type lectin receptor (Mincle) 838:893 The macrophage-inducible C-type lectin receptor (Mincle) is an FcRγ-coupled pathogen recognition receptor that recognizes a wide variety of sugar containing ligands from fungal and bacterial pathogens. 28264048 0 60 theme forsythia 125:133 arg1 -layer 79:84 glycosylated surface (S)-layer 55:84 glycosylated surface (S)-layer of the periodontal pathogen Tannerella forsythia 55:133 Macrophage inducible C-type lectin (Mincle) recognizes glycosylated surface (S)-layer of the periodontal pathogen Tannerella forsythia. 28264048 4 61 theme wide 962:965 arg1 variety 967:973 a wide variety 960:973 a wide variety of sugar containing ligands from fungal and bacterial pathogens 960:1037 The macrophage-inducible C-type lectin receptor (Mincle) is an FcRγ-coupled pathogen recognition receptor that recognizes a wide variety of sugar containing ligands from fungal and bacterial pathogens. 28264048 4 61 theme wide 962:965 arg1 ligands 995:1001 sugar containing ligands 978:1001 sugar containing ligands from fungal and bacterial pathogens 978:1037 The macrophage-inducible C-type lectin receptor (Mincle) is an FcRγ-coupled pathogen recognition receptor that recognizes a wide variety of sugar containing ligands from fungal and bacterial pathogens. 28264048 2 62 with endowed 404:410 arg1 system 454:459 an elaborate protein O-glycosylation system 417:459 an elaborate protein O-glycosylation system that allows the bacterium to express a glycosylated surface (S)-layer comprising two high molecular weight glycoproteins modified with O-linked oligosaccharides 417:620 T. forsythia is a unique Gram-negative organism endowed with an elaborate protein O-glycosylation system that allows the bacterium to express a glycosylated surface (S)-layer comprising two high molecular weight glycoproteins modified with O-linked oligosaccharides. 28264048 2 63 theme high 546:549 arg1 glycoproteins 568:580 two high molecular weight glycoproteins 542:580 two high molecular weight glycoproteins modified with O-linked oligosaccharides 542:620 T. forsythia is a unique Gram-negative organism endowed with an elaborate protein O-glycosylation system that allows the bacterium to express a glycosylated surface (S)-layer comprising two high molecular weight glycoproteins modified with O-linked oligosaccharides. 28264048 6 64 theme Binding 1222:1228 arg1 studies 1230:1236 Binding studies 1222:1236 Binding studies using recombinant Mincle-Fc fusion protein 1222:1279 Binding studies using recombinant Mincle-Fc fusion protein indicated a specific Ca2+-dependent binding of Mincle to T. forsythia S-layer. 28264048 6 65 theme Mincle 1328:1333 arg1 binding 1317:1323 a specific Ca2+-dependent binding 1291:1323 a specific Ca2+-dependent binding of Mincle to T. forsythia S-layer 1291:1357 Binding studies using recombinant Mincle-Fc fusion protein indicated a specific Ca2+-dependent binding of Mincle to T. forsythia S-layer. 28264048 4 66 theme FcRγ-coupled 901:912 arg1 receptor 935:942 an FcRγ-coupled pathogen recognition receptor 898:942 an FcRγ-coupled pathogen recognition receptor that recognizes a wide variety of sugar containing ligands from fungal and bacterial pathogens 898:1037 The macrophage-inducible C-type lectin receptor (Mincle) is an FcRγ-coupled pathogen recognition receptor that recognizes a wide variety of sugar containing ligands from fungal and bacterial pathogens. 28264048 4 66 theme FcRγ-coupled 901:912 arg1 receptor 877:884 The macrophage-inducible C-type lectin receptor 838:884 The macrophage-inducible C-type lectin receptor (Mincle) 838:893 The macrophage-inducible C-type lectin receptor (Mincle) is an FcRγ-coupled pathogen recognition receptor that recognizes a wide variety of sugar containing ligands from fungal and bacterial pathogens. 28264048 2 67 gly glycosylated 500:511 arg1 -layer 524:529 a glycosylated surface (S)-layer 498:529 a glycosylated surface (S)-layer comprising two high molecular weight glycoproteins modified with O-linked oligosaccharides 498:620 T. forsythia is a unique Gram-negative organism endowed with an elaborate protein O-glycosylation system that allows the bacterium to express a glycosylated surface (S)-layer comprising two high molecular weight glycoproteins modified with O-linked oligosaccharides. 28264048 0 68 theme surface 68:74 arg1 -layer 79:84 glycosylated surface (S)-layer 55:84 glycosylated surface (S)-layer of the periodontal pathogen Tannerella forsythia 55:133 Macrophage inducible C-type lectin (Mincle) recognizes glycosylated surface (S)-layer of the periodontal pathogen Tannerella forsythia. 28264048 8 69 theme host 1842:1845 arg1 response 1854:1861 the host immune response 1838:1861 the host immune response 1838:1861 Together, these studies revealed Mincle as an important macrophage receptor involved in the modulation of cytokine responses of macrophages against T. forsythia, and thus may play a critical role in orchestrating the host immune response against the bacterium. 28264048 4 70 theme sugar 978:982 arg1 ligands 995:1001 sugar containing ligands 978:1001 sugar containing ligands from fungal and bacterial pathogens 978:1037 The macrophage-inducible C-type lectin receptor (Mincle) is an FcRγ-coupled pathogen recognition receptor that recognizes a wide variety of sugar containing ligands from fungal and bacterial pathogens. 28264048 0 71 theme S 77:77 arg1 -layer 79:84 glycosylated surface (S)-layer 55:84 glycosylated surface (S)-layer of the periodontal pathogen Tannerella forsythia 55:133 Macrophage inducible C-type lectin (Mincle) recognizes glycosylated surface (S)-layer of the periodontal pathogen Tannerella forsythia. 28264048 1 72 theme tissues 318:324 arg1 destruction 274:284 the destruction 270:284 the destruction of the gum and tooth supporting tissues 270:324 The oral pathogen Tannerella forsythia is implicated in the development of periodontitis, a common inflammatory disease that leads to the destruction of the gum and tooth supporting tissues, often leading to tooth loss. 28264048 2 73 dep O-glycosylation 438:452 arg1 elaborate 420:428 elaborate 420:428 elaborate 420:428 T. forsythia is a unique Gram-negative organism endowed with an elaborate protein O-glycosylation system that allows the bacterium to express a glycosylated surface (S)-layer comprising two high molecular weight glycoproteins modified with O-linked oligosaccharides. 28264048 1 74 theme oral 140:143 arg1 forsythia 165:173 The oral pathogen Tannerella forsythia 136:173 The oral pathogen Tannerella forsythia 136:173 The oral pathogen Tannerella forsythia is implicated in the development of periodontitis, a common inflammatory disease that leads to the destruction of the gum and tooth supporting tissues, often leading to tooth loss. 28264048 4 75 theme ligands 995:1001 arg1 variety 967:973 a wide variety 960:973 a wide variety of sugar containing ligands from fungal and bacterial pathogens 960:1037 The macrophage-inducible C-type lectin receptor (Mincle) is an FcRγ-coupled pathogen recognition receptor that recognizes a wide variety of sugar containing ligands from fungal and bacterial pathogens. 28264048 4 75 theme ligands 995:1001 arg1 ligands 995:1001 sugar containing ligands 978:1001 sugar containing ligands from fungal and bacterial pathogens 978:1037 The macrophage-inducible C-type lectin receptor (Mincle) is an FcRγ-coupled pathogen recognition receptor that recognizes a wide variety of sugar containing ligands from fungal and bacterial pathogens. 28264048 0 76 gly glycosylated 55:66 arg1 -layer 79:84 glycosylated surface (S)-layer 55:84 glycosylated surface (S)-layer of the periodontal pathogen Tannerella forsythia 55:133 Macrophage inducible C-type lectin (Mincle) recognizes glycosylated surface (S)-layer of the periodontal pathogen Tannerella forsythia. 28264048 2 77 theme glycosylated 500:511 arg1 -layer 524:529 a glycosylated surface (S)-layer 498:529 a glycosylated surface (S)-layer comprising two high molecular weight glycoproteins modified with O-linked oligosaccharides 498:620 T. forsythia is a unique Gram-negative organism endowed with an elaborate protein O-glycosylation system that allows the bacterium to express a glycosylated surface (S)-layer comprising two high molecular weight glycoproteins modified with O-linked oligosaccharides. 28264048 0 78 theme inducible 11:19 arg1 Mincle 36:41 Mincle 36:41 Mincle 36:41 Macrophage inducible C-type lectin (Mincle) recognizes glycosylated surface (S)-layer of the periodontal pathogen Tannerella forsythia. 28264048 0 78 theme inducible 11:19 arg1 lectin 28:33 Macrophage inducible C-type lectin 0:33 Macrophage inducible C-type lectin (Mincle) 0:42 Macrophage inducible C-type lectin (Mincle) recognizes glycosylated surface (S)-layer of the periodontal pathogen Tannerella forsythia. 28264048 5 79 theme response 1175:1182 arg1 modulation 1152:1161 modulation 1152:1161 modulation of cytokine response of macrophages against the bacterium 1152:1219 In this study, we aimed to determine if Mincle might be involved in the recognition of T. forsythia S-layer and modulation of cytokine response of macrophages against the bacterium. 28264048 5 79 theme response 1175:1182 arg1 recognition 1112:1122 the recognition 1108:1122 the recognition of T. forsythia S-layer 1108:1146 In this study, we aimed to determine if Mincle might be involved in the recognition of T. forsythia S-layer and modulation of cytokine response of macrophages against the bacterium. 28264048 7 80 from S-layer 1616:1622 arg1 induction 1493:1501 the induction 1489:1501 the induction of both pro- and anti-inflammatory cytokine secretion in macrophages stimulated with T. forsythia 1489:1599 Subsequent experiments with Mincle-expressing and Mincle-knockdown macrophages revealed a role for Mincle/S-layer interaction in the induction of both pro- and anti-inflammatory cytokine secretion in macrophages stimulated with T. forsythia as well as its S-layer. 28264048 2 81 theme endowed 404:410 arg1 forsythia 359:367 T. forsythia 356:367 T. forsythia 356:367 T. forsythia is a unique Gram-negative organism endowed with an elaborate protein O-glycosylation system that allows the bacterium to express a glycosylated surface (S)-layer comprising two high molecular weight glycoproteins modified with O-linked oligosaccharides. 28264048 2 81 theme endowed 404:410 arg1 organism 395:402 a unique Gram-negative organism 372:402 a unique Gram-negative organism endowed with an elaborate protein O-glycosylation system that allows the bacterium to express a glycosylated surface (S)-layer comprising two high molecular weight glycoproteins modified with O-linked oligosaccharides 372:620 T. forsythia is a unique Gram-negative organism endowed with an elaborate protein O-glycosylation system that allows the bacterium to express a glycosylated surface (S)-layer comprising two high molecular weight glycoproteins modified with O-linked oligosaccharides. 28264048 2 82 theme Gram-negative 381:393 arg1 forsythia 359:367 T. forsythia 356:367 T. forsythia 356:367 T. forsythia is a unique Gram-negative organism endowed with an elaborate protein O-glycosylation system that allows the bacterium to express a glycosylated surface (S)-layer comprising two high molecular weight glycoproteins modified with O-linked oligosaccharides. 28264048 2 82 theme Gram-negative 381:393 arg1 organism 395:402 a unique Gram-negative organism 372:402 a unique Gram-negative organism endowed with an elaborate protein O-glycosylation system that allows the bacterium to express a glycosylated surface (S)-layer comprising two high molecular weight glycoproteins modified with O-linked oligosaccharides 372:620 T. forsythia is a unique Gram-negative organism endowed with an elaborate protein O-glycosylation system that allows the bacterium to express a glycosylated surface (S)-layer comprising two high molecular weight glycoproteins modified with O-linked oligosaccharides. 28264048 5 83 theme macrophages 1187:1197 arg1 response 1175:1182 cytokine response 1166:1182 cytokine response of macrophages against the bacterium 1166:1219 In this study, we aimed to determine if Mincle might be involved in the recognition of T. forsythia S-layer and modulation of cytokine response of macrophages against the bacterium. 28264048 4 84 theme fungal 1008:1013 arg1 pathogens 1029:1037 fungal and bacterial pathogens 1008:1037 pathogens 1029:1037 The macrophage-inducible C-type lectin receptor (Mincle) is an FcRγ-coupled pathogen recognition receptor that recognizes a wide variety of sugar containing ligands from fungal and bacterial pathogens. 28264048 3 85 theme T. 627:628 arg1 S-layer 640:646 The T. forsythia S-layer 623:646 The T. forsythia S-layer 623:646 The T. forsythia S-layer has been implicated in the modulation of cytokine responses of antigen presenting cells, such as macrophages, that play a significant role during inflammation associated with periodontitis. 28264048 1 86 theme gum 293:295 arg1 tissues 318:324 the gum and tooth supporting tissues 289:324 the gum and tooth supporting tissues 289:324 The oral pathogen Tannerella forsythia is implicated in the development of periodontitis, a common inflammatory disease that leads to the destruction of the gum and tooth supporting tissues, often leading to tooth loss. 28264048 4 87 theme C-type 863:868 arg1 receptor 935:942 an FcRγ-coupled pathogen recognition receptor 898:942 an FcRγ-coupled pathogen recognition receptor that recognizes a wide variety of sugar containing ligands from fungal and bacterial pathogens 898:1037 The macrophage-inducible C-type lectin receptor (Mincle) is an FcRγ-coupled pathogen recognition receptor that recognizes a wide variety of sugar containing ligands from fungal and bacterial pathogens. 28264048 4 87 theme C-type 863:868 arg1 Mincle 887:892 Mincle 887:892 Mincle 887:892 The macrophage-inducible C-type lectin receptor (Mincle) is an FcRγ-coupled pathogen recognition receptor that recognizes a wide variety of sugar containing ligands from fungal and bacterial pathogens. 28264048 4 87 theme C-type 863:868 arg1 receptor 877:884 The macrophage-inducible C-type lectin receptor 838:884 The macrophage-inducible C-type lectin receptor (Mincle) 838:893 The macrophage-inducible C-type lectin receptor (Mincle) is an FcRγ-coupled pathogen recognition receptor that recognizes a wide variety of sugar containing ligands from fungal and bacterial pathogens. 28264048 4 88 theme bacterial 1019:1027 arg1 pathogens 1029:1037 fungal and bacterial pathogens 1008:1037 pathogens 1029:1037 The macrophage-inducible C-type lectin receptor (Mincle) is an FcRγ-coupled pathogen recognition receptor that recognizes a wide variety of sugar containing ligands from fungal and bacterial pathogens. 28264048 1 89 theme tooth 301:305 arg1 tissues 318:324 the gum and tooth supporting tissues 289:324 the gum and tooth supporting tissues 289:324 The oral pathogen Tannerella forsythia is implicated in the development of periodontitis, a common inflammatory disease that leads to the destruction of the gum and tooth supporting tissues, often leading to tooth loss. 28264048 8 90 theme responses 1740:1748 arg1 modulation 1717:1726 the modulation 1713:1726 the modulation of cytokine responses of macrophages against T. forsythia 1713:1784 Together, these studies revealed Mincle as an important macrophage receptor involved in the modulation of cytokine responses of macrophages against T. forsythia, and thus may play a critical role in orchestrating the host immune response against the bacterium. 28264048 8 91 theme macrophage 1681:1690 arg1 receptor 1692:1699 an important macrophage receptor 1668:1699 an important macrophage receptor involved in the modulation of cytokine responses of macrophages against T. forsythia 1668:1784 Together, these studies revealed Mincle as an important macrophage receptor involved in the modulation of cytokine responses of macrophages against T. forsythia, and thus may play a critical role in orchestrating the host immune response against the bacterium. 28264048 8 91 theme macrophage 1681:1690 arg1 Mincle 1658:1663 Mincle 1658:1663 Mincle 1658:1663 Together, these studies revealed Mincle as an important macrophage receptor involved in the modulation of cytokine responses of macrophages against T. forsythia, and thus may play a critical role in orchestrating the host immune response against the bacterium. 28264048 3 92 theme cytokine 689:696 arg1 responses 698:706 cytokine responses 689:706 cytokine responses of antigen presenting cells, such as macrophages, that play a significant role during inflammation associated with periodontitis 689:835 The T. forsythia S-layer has been implicated in the modulation of cytokine responses of antigen presenting cells, such as macrophages, that play a significant role during inflammation associated with periodontitis. 28264048 8 93 theme macrophages 1753:1763 arg1 responses 1740:1748 cytokine responses 1731:1748 cytokine responses of macrophages against T. forsythia 1731:1784 Together, these studies revealed Mincle as an important macrophage receptor involved in the modulation of cytokine responses of macrophages against T. forsythia, and thus may play a critical role in orchestrating the host immune response against the bacterium. 28264048 1 94 theme common 228:233 arg1 disease 248:254 a common inflammatory disease 226:254 a common inflammatory disease that leads to the destruction of the gum and tooth supporting tissues, often leading to tooth loss 226:353 The oral pathogen Tannerella forsythia is implicated in the development of periodontitis, a common inflammatory disease that leads to the destruction of the gum and tooth supporting tissues, often leading to tooth loss. 28264048 1 94 theme common 228:233 arg1 periodontitis 211:223 periodontitis 211:223 periodontitis 211:223 The oral pathogen Tannerella forsythia is implicated in the development of periodontitis, a common inflammatory disease that leads to the destruction of the gum and tooth supporting tissues, often leading to tooth loss. 26323930 9 0 theme MUC13 1218:1222 arg1 expression 1204:1213 expression 1204:1213 expression of MUC13 1204:1222 When combining expression of MUC13 with MUC20, we found that the median survival time of patients with low MUC13/high MUC20 expression was significantly shorter than that of patients with high MUC13/low MUC20 expression (27.7 months vs. 59.5 months, P = 0.021). 26323930 9 1 theme MUC20 1307:1311 arg1 expression 1313:1322 low MUC13/high MUC20 expression 1292:1322 low MUC13/high MUC20 expression 1292:1322 When combining expression of MUC13 with MUC20, we found that the median survival time of patients with low MUC13/high MUC20 expression was significantly shorter than that of patients with high MUC13/low MUC20 expression (27.7 months vs. 59.5 months, P = 0.021). 26323930 4 2 theme METHODS 629:635 arg1 Immunohistochemistry 637:656 MATERIALS AND METHODS Immunohistochemistry 615:656 MATERIALS AND METHODS Immunohistochemistry 615:656 MATERIALS AND METHODS Immunohistochemistry was used to detect the expressions of MUC13 and MUC20 in 186 patients with ESCC who received neoadjuvant chemotherapy followed by surgery. 26323930 11 3 theme MUC13/MUC20 1662:1672 arg1 expression 1674:1683 MUC13/MUC20 expression 1662:1683 MUC13/MUC20 expression 1662:1683 CONCLUSION A combination of MUC13/MUC20 expression was a potential prognostic marker for patients with ESCC, who received neoadjuvant chemotherapy followed by surgery. 26323930 10 4 theme = 1575:1575 arg1 0.531 1577:1581 hazard ratios = 0.531 1561:1581 hazard ratios = 0.531 1561:1581 Multivariate analysis showed that combination of MUC13/MUC20 expression was an independent prognostic factor (hazard ratios = 0.531, 95% confidence interval: 0.299-0.944, P = 0.031). 26323930 0 5 from expression 4:13 arg1 carcinoma 96:104 esophageal squamous cell carcinoma 71:104 esophageal squamous cell carcinoma 71:104 The expression and prognostic significance of Mucin 13 and Mucin 20 in esophageal squamous cell carcinoma. 26323930 9 6 theme high 1377:1380 arg1 expression 1398:1407 high MUC13/low MUC20 expression 1377:1407 high MUC13/low MUC20 expression 1377:1407 When combining expression of MUC13 with MUC20, we found that the median survival time of patients with low MUC13/high MUC20 expression was significantly shorter than that of patients with high MUC13/low MUC20 expression (27.7 months vs. 59.5 months, P = 0.021). 26323930 4 7 used used 662:665 arg2 Immunohistochemistry 637:656 MATERIALS AND METHODS Immunohistochemistry 615:656 MATERIALS AND METHODS Immunohistochemistry 615:656 MATERIALS AND METHODS Immunohistochemistry was used to detect the expressions of MUC13 and MUC20 in 186 patients with ESCC who received neoadjuvant chemotherapy followed by surgery. 26323930 6 8 theme MUC20 938:942 arg1 expression 914:923 The expression 910:923 The expression of MUC13 and MUC20 in ESCC 910:950 RESULTS The expression of MUC13 and MUC20 in ESCC mainly occurred in the cytoplasm. 26323930 0 9 theme squamous 82:89 arg1 carcinoma 96:104 esophageal squamous cell carcinoma 71:104 esophageal squamous cell carcinoma 71:104 The expression and prognostic significance of Mucin 13 and Mucin 20 in esophageal squamous cell carcinoma. 26323930 7 10 theme MUC13 1025:1029 arg1 expression 1031:1040 high MUC13 expression 1020:1040 high MUC13 expression 1020:1040 Among the 186 subjects, 53.8% had high MUC13 expression and 38.2% had high MUC20 expression. 26323930 10 11 dep = 1575:1575 arg1 ratios 1568:1573 ratios 1568:1573 ratios 1568:1573 Multivariate analysis showed that combination of MUC13/MUC20 expression was an independent prognostic factor (hazard ratios = 0.531, 95% confidence interval: 0.299-0.944, P = 0.031). 26323930 4 12 with patients 719:726 arg1 ESCC 733:736 ESCC 733:736 ESCC 733:736 MATERIALS AND METHODS Immunohistochemistry was used to detect the expressions of MUC13 and MUC20 in 186 patients with ESCC who received neoadjuvant chemotherapy followed by surgery. 26323930 0 13 theme esophageal 71:80 arg1 carcinoma 96:104 esophageal squamous cell carcinoma 71:104 esophageal squamous cell carcinoma 71:104 The expression and prognostic significance of Mucin 13 and Mucin 20 in esophageal squamous cell carcinoma. 26323930 1 14 gly glycoprotein 205:216 arg1 Mucin 118:122 BACKGROUND Mucin 13 107:125 BACKGROUND Mucin 13 (MUC13) 107:133 BACKGROUND Mucin 13 (MUC13) and Mucin 20 (MUC20) are high molecular weight transmembrane O-linked glycoprotein secreted by epithelium and are widely overexpressed in epithelial tumor cells. 26323930 1 14 gly glycoprotein 205:216 arg1 Mucin 139:143 Mucin 20 139:146 Mucin 20 (MUC20) 139:154 BACKGROUND Mucin 13 (MUC13) and Mucin 20 (MUC20) are high molecular weight transmembrane O-linked glycoprotein secreted by epithelium and are widely overexpressed in epithelial tumor cells. 26323930 1 14 gly glycoprotein 205:216 arg1 glycoprotein 205:216 high molecular weight transmembrane O-linked glycoprotein 160:216 high molecular weight transmembrane O-linked glycoprotein secreted by epithelium 160:239 BACKGROUND Mucin 13 (MUC13) and Mucin 20 (MUC20) are high molecular weight transmembrane O-linked glycoprotein secreted by epithelium and are widely overexpressed in epithelial tumor cells. 26323930 4 15 theme MUC13 696:700 arg1 expressions 681:691 the expressions 677:691 the expressions of MUC13 and MUC20 in 186 patients with ESCC who received neoadjuvant chemotherapy followed by surgery 677:794 MATERIALS AND METHODS Immunohistochemistry was used to detect the expressions of MUC13 and MUC20 in 186 patients with ESCC who received neoadjuvant chemotherapy followed by surgery. 26323930 6 16 theme MUC13 928:932 arg1 expression 914:923 The expression 910:923 The expression of MUC13 and MUC20 in ESCC 910:950 RESULTS The expression of MUC13 and MUC20 in ESCC mainly occurred in the cytoplasm. 26323930 9 17 with patients 1363:1370 arg1 expression 1398:1407 high MUC13/low MUC20 expression 1377:1407 high MUC13/low MUC20 expression 1377:1407 When combining expression of MUC13 with MUC20, we found that the median survival time of patients with low MUC13/high MUC20 expression was significantly shorter than that of patients with high MUC13/low MUC20 expression (27.7 months vs. 59.5 months, P = 0.021). 26323930 9 18 with patients 1278:1285 arg1 expression 1313:1322 low MUC13/high MUC20 expression 1292:1322 low MUC13/high MUC20 expression 1292:1322 When combining expression of MUC13 with MUC20, we found that the median survival time of patients with low MUC13/high MUC20 expression was significantly shorter than that of patients with high MUC13/low MUC20 expression (27.7 months vs. 59.5 months, P = 0.021). 26323930 2 19 theme prognostic 356:365 arg1 biomarkers 377:386 prognostic molecular biomarkers 356:386 prognostic molecular biomarkers of some epithelial tumors 356:412 Previously, it has been reported that MUC13 and MUC20 were prognostic molecular biomarkers of some epithelial tumors, but few has studied the relations between MUC13 or MUC20 expression and the prognosis of patients with esophageal squamous cell carcinoma (ESCC). 26323930 0 20 theme cell 91:94 arg1 carcinoma 96:104 esophageal squamous cell carcinoma 71:104 esophageal squamous cell carcinoma 71:104 The expression and prognostic significance of Mucin 13 and Mucin 20 in esophageal squamous cell carcinoma. 26323930 10 21 theme interval 1599:1606 arg1 % 1586:1586 95% 1584:1586 95% confidence interval 1584:1606 Multivariate analysis showed that combination of MUC13/MUC20 expression was an independent prognostic factor (hazard ratios = 0.531, 95% confidence interval: 0.299-0.944, P = 0.031). 26323930 7 22 theme high 1020:1023 arg1 expression 1031:1040 high MUC13 expression 1020:1040 high MUC13 expression 1020:1040 Among the 186 subjects, 53.8% had high MUC13 expression and 38.2% had high MUC20 expression. 26323930 1 23 link O-linked 196:203 arg1 Mucin 118:122 BACKGROUND Mucin 13 107:125 BACKGROUND Mucin 13 (MUC13) 107:133 BACKGROUND Mucin 13 (MUC13) and Mucin 20 (MUC20) are high molecular weight transmembrane O-linked glycoprotein secreted by epithelium and are widely overexpressed in epithelial tumor cells. 26323930 1 23 link O-linked 196:203 arg1 Mucin 139:143 Mucin 20 139:146 Mucin 20 (MUC20) 139:154 BACKGROUND Mucin 13 (MUC13) and Mucin 20 (MUC20) are high molecular weight transmembrane O-linked glycoprotein secreted by epithelium and are widely overexpressed in epithelial tumor cells. 26323930 1 23 link O-linked 196:203 arg1 glycoprotein 205:216 high molecular weight transmembrane O-linked glycoprotein 160:216 high molecular weight transmembrane O-linked glycoprotein secreted by epithelium 160:239 BACKGROUND Mucin 13 (MUC13) and Mucin 20 (MUC20) are high molecular weight transmembrane O-linked glycoprotein secreted by epithelium and are widely overexpressed in epithelial tumor cells. 26323930 4 24 theme MUC20 706:710 arg1 expressions 681:691 the expressions 677:691 the expressions of MUC13 and MUC20 in 186 patients with ESCC who received neoadjuvant chemotherapy followed by surgery 677:794 MATERIALS AND METHODS Immunohistochemistry was used to detect the expressions of MUC13 and MUC20 in 186 patients with ESCC who received neoadjuvant chemotherapy followed by surgery. 26323930 11 25 theme expression 1674:1683 arg1 marker 1712:1717 a potential prognostic marker 1689:1717 a potential prognostic marker for patients with ESCC, who received neoadjuvant chemotherapy followed by surgery 1689:1799 CONCLUSION A combination of MUC13/MUC20 expression was a potential prognostic marker for patients with ESCC, who received neoadjuvant chemotherapy followed by surgery. 26323930 11 25 theme expression 1674:1683 arg1 combination 1647:1657 A combination 1645:1657 A combination of MUC13/MUC20 expression 1645:1683 CONCLUSION A combination of MUC13/MUC20 expression was a potential prognostic marker for patients with ESCC, who received neoadjuvant chemotherapy followed by surgery. 26323930 10 26 theme Multivariate 1451:1462 arg1 analysis 1464:1471 Multivariate analysis 1451:1471 Multivariate analysis 1451:1471 Multivariate analysis showed that combination of MUC13/MUC20 expression was an independent prognostic factor (hazard ratios = 0.531, 95% confidence interval: 0.299-0.944, P = 0.031). 26323930 0 27 from significance 30:41 arg1 carcinoma 96:104 esophageal squamous cell carcinoma 71:104 esophageal squamous cell carcinoma 71:104 The expression and prognostic significance of Mucin 13 and Mucin 20 in esophageal squamous cell carcinoma. 26323930 4 28 from expressions 681:691 arg1 patients 719:726 186 patients 715:726 186 patients with ESCC who received neoadjuvant chemotherapy followed by surgery 715:794 MATERIALS AND METHODS Immunohistochemistry was used to detect the expressions of MUC13 and MUC20 in 186 patients with ESCC who received neoadjuvant chemotherapy followed by surgery. 26323930 10 29 theme MUC13/MUC20 1500:1510 arg1 expression 1512:1521 MUC13/MUC20 expression 1500:1521 MUC13/MUC20 expression 1500:1521 Multivariate analysis showed that combination of MUC13/MUC20 expression was an independent prognostic factor (hazard ratios = 0.531, 95% confidence interval: 0.299-0.944, P = 0.031). 26323930 10 30 theme expression 1512:1521 arg1 factor 1553:1558 an independent prognostic factor 1527:1558 an independent prognostic factor 1527:1558 Multivariate analysis showed that combination of MUC13/MUC20 expression was an independent prognostic factor (hazard ratios = 0.531, 95% confidence interval: 0.299-0.944, P = 0.031). 26323930 10 30 theme expression 1512:1521 arg1 combination 1485:1495 combination 1485:1495 combination of MUC13/MUC20 expression 1485:1521 Multivariate analysis showed that combination of MUC13/MUC20 expression was an independent prognostic factor (hazard ratios = 0.531, 95% confidence interval: 0.299-0.944, P = 0.031). 26323930 11 31 theme potential 1691:1699 arg1 combination 1647:1657 A combination 1645:1657 A combination of MUC13/MUC20 expression 1645:1683 CONCLUSION A combination of MUC13/MUC20 expression was a potential prognostic marker for patients with ESCC, who received neoadjuvant chemotherapy followed by surgery. 26323930 11 31 theme potential 1691:1699 arg1 marker 1712:1717 a potential prognostic marker 1689:1717 a potential prognostic marker for patients with ESCC, who received neoadjuvant chemotherapy followed by surgery 1689:1799 CONCLUSION A combination of MUC13/MUC20 expression was a potential prognostic marker for patients with ESCC, who received neoadjuvant chemotherapy followed by surgery. 26323930 9 32 dep = 1441:1441 arg1 months 1415:1420 27.7 months 1410:1420 27.7 months 1410:1420 When combining expression of MUC13 with MUC20, we found that the median survival time of patients with low MUC13/high MUC20 expression was significantly shorter than that of patients with high MUC13/low MUC20 expression (27.7 months vs. 59.5 months, P = 0.021). 26323930 9 32 dep = 1441:1441 arg1 months 1431:1436 59.5 months 1426:1436 59.5 months 1426:1436 When combining expression of MUC13 with MUC20, we found that the median survival time of patients with low MUC13/high MUC20 expression was significantly shorter than that of patients with high MUC13/low MUC20 expression (27.7 months vs. 59.5 months, P = 0.021). 26323930 8 33 theme long-term 1169:1177 arg1 survival 1179:1186 long-term survival 1169:1186 long-term survival 1169:1186 Univariate analysis showed that neither MUC13 nor MUC20 was significantly associated with long-term survival. 26323930 0 34 theme prognostic 19:28 arg1 significance 30:41 prognostic significance 19:41 prognostic significance 19:41 The expression and prognostic significance of Mucin 13 and Mucin 20 in esophageal squamous cell carcinoma. 26323930 8 35 theme Univariate 1079:1088 arg1 analysis 1090:1097 Univariate analysis 1079:1097 Univariate analysis 1079:1097 Univariate analysis showed that neither MUC13 nor MUC20 was significantly associated with long-term survival. 26323930 5 36 theme patients 892:899 arg1 expression 849:858 MUC13 or MUC20 expression 834:858 MUC13 or MUC20 expression 834:858 We analyzed the correlations between MUC13 or MUC20 expression and long-term survival of these patients. 26323930 5 36 theme patients 892:899 arg1 survival 874:881 long-term survival 864:881 long-term survival 864:881 We analyzed the correlations between MUC13 or MUC20 expression and long-term survival of these patients. 26323930 7 37 contain had 1052:1054 arg1 % 1050:1050 38.2% 1046:1050 38.2% 1046:1050 Among the 186 subjects, 53.8% had high MUC13 expression and 38.2% had high MUC20 expression. 26323930 7 37 contain had 1052:1054 arg2 expression 1067:1076 high MUC20 expression 1056:1076 high MUC20 expression 1056:1076 Among the 186 subjects, 53.8% had high MUC13 expression and 38.2% had high MUC20 expression. 26323930 2 38 theme molecular 367:375 arg1 biomarkers 377:386 prognostic molecular biomarkers 356:386 prognostic molecular biomarkers of some epithelial tumors 356:412 Previously, it has been reported that MUC13 and MUC20 were prognostic molecular biomarkers of some epithelial tumors, but few has studied the relations between MUC13 or MUC20 expression and the prognosis of patients with esophageal squamous cell carcinoma (ESCC). 26323930 2 39 theme epithelial 396:405 arg1 tumors 407:412 some epithelial tumors 391:412 some epithelial tumors 391:412 Previously, it has been reported that MUC13 and MUC20 were prognostic molecular biomarkers of some epithelial tumors, but few has studied the relations between MUC13 or MUC20 expression and the prognosis of patients with esophageal squamous cell carcinoma (ESCC). 26323930 9 40 theme survival 1261:1268 arg1 shorter 1342:1348 shorter 1342:1348 shorter 1342:1348 When combining expression of MUC13 with MUC20, we found that the median survival time of patients with low MUC13/high MUC20 expression was significantly shorter than that of patients with high MUC13/low MUC20 expression (27.7 months vs. 59.5 months, P = 0.021). 26323930 9 40 theme survival 1261:1268 arg1 time 1270:1273 the median survival time 1250:1273 the median survival time of patients with low MUC13/high MUC20 expression 1250:1322 When combining expression of MUC13 with MUC20, we found that the median survival time of patients with low MUC13/high MUC20 expression was significantly shorter than that of patients with high MUC13/low MUC20 expression (27.7 months vs. 59.5 months, P = 0.021). 26323930 2 41 theme patients 504:511 arg1 relations 439:447 the relations 435:447 the relations between MUC13 or MUC20 expression 435:481 Previously, it has been reported that MUC13 and MUC20 were prognostic molecular biomarkers of some epithelial tumors, but few has studied the relations between MUC13 or MUC20 expression and the prognosis of patients with esophageal squamous cell carcinoma (ESCC). 26323930 2 41 theme patients 504:511 arg1 prognosis 491:499 the prognosis 487:499 the prognosis of patients with esophageal squamous cell carcinoma (ESCC) 487:558 Previously, it has been reported that MUC13 and MUC20 were prognostic molecular biomarkers of some epithelial tumors, but few has studied the relations between MUC13 or MUC20 expression and the prognosis of patients with esophageal squamous cell carcinoma (ESCC). 26323930 3 42 theme study 582:586 arg1 aim 571:573 the aim 567:573 the aim of our study 567:586 Thus, the aim of our study was to explore this issue. 26323930 9 43 theme MUC20 1392:1396 arg1 expression 1398:1407 high MUC13/low MUC20 expression 1377:1407 high MUC13/low MUC20 expression 1377:1407 When combining expression of MUC13 with MUC20, we found that the median survival time of patients with low MUC13/high MUC20 expression was significantly shorter than that of patients with high MUC13/low MUC20 expression (27.7 months vs. 59.5 months, P = 0.021). 26323930 7 44 theme high 1056:1059 arg1 expression 1067:1076 high MUC20 expression 1056:1076 high MUC20 expression 1056:1076 Among the 186 subjects, 53.8% had high MUC13 expression and 38.2% had high MUC20 expression. 26323930 11 45 with patients 1723:1730 arg1 ESCC 1737:1740 ESCC 1737:1740 ESCC 1737:1740 CONCLUSION A combination of MUC13/MUC20 expression was a potential prognostic marker for patients with ESCC, who received neoadjuvant chemotherapy followed by surgery. 26323930 7 46 contain had 1016:1018 arg2 expression 1031:1040 high MUC13 expression 1020:1040 high MUC13 expression 1020:1040 Among the 186 subjects, 53.8% had high MUC13 expression and 38.2% had high MUC20 expression. 26323930 7 46 contain had 1016:1018 arg1 % 1014:1014 53.8% 1010:1014 53.8% 1010:1014 Among the 186 subjects, 53.8% had high MUC13 expression and 38.2% had high MUC20 expression. 26323930 1 47 theme high 160:163 arg1 weight 175:180 high molecular weight 160:180 high molecular weight transmembrane O-linked glycoprotein secreted by epithelium 160:239 BACKGROUND Mucin 13 (MUC13) and Mucin 20 (MUC20) are high molecular weight transmembrane O-linked glycoprotein secreted by epithelium and are widely overexpressed in epithelial tumor cells. 26323930 7 48 theme MUC20 1061:1065 arg1 expression 1067:1076 high MUC20 expression 1056:1076 high MUC20 expression 1056:1076 Among the 186 subjects, 53.8% had high MUC13 expression and 38.2% had high MUC20 expression. 26323930 1 49 theme epithelial 273:282 arg1 cells 290:294 epithelial tumor cells 273:294 epithelial tumor cells 273:294 BACKGROUND Mucin 13 (MUC13) and Mucin 20 (MUC20) are high molecular weight transmembrane O-linked glycoprotein secreted by epithelium and are widely overexpressed in epithelial tumor cells. 26323930 6 50 from expression 914:923 arg1 ESCC 947:950 ESCC 947:950 ESCC 947:950 RESULTS The expression of MUC13 and MUC20 in ESCC mainly occurred in the cytoplasm. 26323930 11 51 dep CONCLUSION 1634:1643 arg1 combination 1647:1657 A combination 1645:1657 A combination of MUC13/MUC20 expression 1645:1683 CONCLUSION A combination of MUC13/MUC20 expression was a potential prognostic marker for patients with ESCC, who received neoadjuvant chemotherapy followed by surgery. 26323930 11 51 dep CONCLUSION 1634:1643 arg1 marker 1712:1717 a potential prognostic marker 1689:1717 a potential prognostic marker for patients with ESCC, who received neoadjuvant chemotherapy followed by surgery 1689:1799 CONCLUSION A combination of MUC13/MUC20 expression was a potential prognostic marker for patients with ESCC, who received neoadjuvant chemotherapy followed by surgery. 26323930 2 52 theme tumors 407:412 arg1 biomarkers 377:386 prognostic molecular biomarkers 356:386 prognostic molecular biomarkers of some epithelial tumors 356:412 Previously, it has been reported that MUC13 and MUC20 were prognostic molecular biomarkers of some epithelial tumors, but few has studied the relations between MUC13 or MUC20 expression and the prognosis of patients with esophageal squamous cell carcinoma (ESCC). 26323930 2 53 theme MUC20 466:470 arg1 expression 472:481 MUC20 expression 466:481 MUC20 expression 466:481 Previously, it has been reported that MUC13 and MUC20 were prognostic molecular biomarkers of some epithelial tumors, but few has studied the relations between MUC13 or MUC20 expression and the prognosis of patients with esophageal squamous cell carcinoma (ESCC). 26323930 10 54 theme independent 1530:1540 arg1 combination 1485:1495 combination 1485:1495 combination of MUC13/MUC20 expression 1485:1521 Multivariate analysis showed that combination of MUC13/MUC20 expression was an independent prognostic factor (hazard ratios = 0.531, 95% confidence interval: 0.299-0.944, P = 0.031). 26323930 10 54 theme independent 1530:1540 arg1 factor 1553:1558 an independent prognostic factor 1527:1558 an independent prognostic factor 1527:1558 Multivariate analysis showed that combination of MUC13/MUC20 expression was an independent prognostic factor (hazard ratios = 0.531, 95% confidence interval: 0.299-0.944, P = 0.031). 26323930 1 55 theme tumor 284:288 arg1 cells 290:294 epithelial tumor cells 273:294 epithelial tumor cells 273:294 BACKGROUND Mucin 13 (MUC13) and Mucin 20 (MUC20) are high molecular weight transmembrane O-linked glycoprotein secreted by epithelium and are widely overexpressed in epithelial tumor cells. 26323930 9 56 theme median 1254:1259 arg1 shorter 1342:1348 shorter 1342:1348 shorter 1342:1348 When combining expression of MUC13 with MUC20, we found that the median survival time of patients with low MUC13/high MUC20 expression was significantly shorter than that of patients with high MUC13/low MUC20 expression (27.7 months vs. 59.5 months, P = 0.021). 26323930 9 56 theme median 1254:1259 arg1 time 1270:1273 the median survival time 1250:1273 the median survival time of patients with low MUC13/high MUC20 expression 1250:1322 When combining expression of MUC13 with MUC20, we found that the median survival time of patients with low MUC13/high MUC20 expression was significantly shorter than that of patients with high MUC13/low MUC20 expression (27.7 months vs. 59.5 months, P = 0.021). 26323930 0 57 theme Mucin 46:50 arg1 expression 4:13 expression 4:13 expression 4:13 The expression and prognostic significance of Mucin 13 and Mucin 20 in esophageal squamous cell carcinoma. 26323930 0 57 theme Mucin 46:50 arg1 significance 30:41 prognostic significance 19:41 prognostic significance 19:41 The expression and prognostic significance of Mucin 13 and Mucin 20 in esophageal squamous cell carcinoma. 26323930 2 58 theme cell 538:541 arg1 ESCC 554:557 ESCC 554:557 ESCC 554:557 Previously, it has been reported that MUC13 and MUC20 were prognostic molecular biomarkers of some epithelial tumors, but few has studied the relations between MUC13 or MUC20 expression and the prognosis of patients with esophageal squamous cell carcinoma (ESCC). 26323930 2 58 theme cell 538:541 arg1 carcinoma 543:551 esophageal squamous cell carcinoma 518:551 esophageal squamous cell carcinoma (ESCC) 518:558 Previously, it has been reported that MUC13 and MUC20 were prognostic molecular biomarkers of some epithelial tumors, but few has studied the relations between MUC13 or MUC20 expression and the prognosis of patients with esophageal squamous cell carcinoma (ESCC). 26323930 4 59 theme neoadjuvant 751:761 arg1 chemotherapy 763:774 neoadjuvant chemotherapy 751:774 neoadjuvant chemotherapy followed by surgery 751:794 MATERIALS AND METHODS Immunohistochemistry was used to detect the expressions of MUC13 and MUC20 in 186 patients with ESCC who received neoadjuvant chemotherapy followed by surgery. 26323930 1 60 theme BACKGROUND 107:116 arg1 Mucin 118:122 BACKGROUND Mucin 13 107:125 BACKGROUND Mucin 13 (MUC13) 107:133 BACKGROUND Mucin 13 (MUC13) and Mucin 20 (MUC20) are high molecular weight transmembrane O-linked glycoprotein secreted by epithelium and are widely overexpressed in epithelial tumor cells. 26323930 1 60 theme BACKGROUND 107:116 arg1 MUC13 128:132 MUC13 128:132 MUC13 128:132 BACKGROUND Mucin 13 (MUC13) and Mucin 20 (MUC20) are high molecular weight transmembrane O-linked glycoprotein secreted by epithelium and are widely overexpressed in epithelial tumor cells. 26323930 1 60 theme BACKGROUND 107:116 arg1 Mucin 139:143 Mucin 20 139:146 Mucin 20 (MUC20) 139:154 BACKGROUND Mucin 13 (MUC13) and Mucin 20 (MUC20) are high molecular weight transmembrane O-linked glycoprotein secreted by epithelium and are widely overexpressed in epithelial tumor cells. 26323930 1 60 theme BACKGROUND 107:116 arg1 glycoprotein 205:216 high molecular weight transmembrane O-linked glycoprotein 160:216 high molecular weight transmembrane O-linked glycoprotein secreted by epithelium 160:239 BACKGROUND Mucin 13 (MUC13) and Mucin 20 (MUC20) are high molecular weight transmembrane O-linked glycoprotein secreted by epithelium and are widely overexpressed in epithelial tumor cells. 26323930 9 61 theme low 1292:1294 arg1 expression 1313:1322 low MUC13/high MUC20 expression 1292:1322 low MUC13/high MUC20 expression 1292:1322 When combining expression of MUC13 with MUC20, we found that the median survival time of patients with low MUC13/high MUC20 expression was significantly shorter than that of patients with high MUC13/low MUC20 expression (27.7 months vs. 59.5 months, P = 0.021). 26323930 2 62 theme squamous 529:536 arg1 ESCC 554:557 ESCC 554:557 ESCC 554:557 Previously, it has been reported that MUC13 and MUC20 were prognostic molecular biomarkers of some epithelial tumors, but few has studied the relations between MUC13 or MUC20 expression and the prognosis of patients with esophageal squamous cell carcinoma (ESCC). 26323930 2 62 theme squamous 529:536 arg1 carcinoma 543:551 esophageal squamous cell carcinoma 518:551 esophageal squamous cell carcinoma (ESCC) 518:558 Previously, it has been reported that MUC13 and MUC20 were prognostic molecular biomarkers of some epithelial tumors, but few has studied the relations between MUC13 or MUC20 expression and the prognosis of patients with esophageal squamous cell carcinoma (ESCC). 26323930 6 63 dep RESULTS 902:908 arg1 occurred 959:966 occurred 959:966 occurred in the cytoplasm 959:983 RESULTS The expression of MUC13 and MUC20 in ESCC mainly occurred in the cytoplasm. 26323930 11 64 theme neoadjuvant 1756:1766 arg1 chemotherapy 1768:1779 neoadjuvant chemotherapy 1756:1779 neoadjuvant chemotherapy followed by surgery 1756:1799 CONCLUSION A combination of MUC13/MUC20 expression was a potential prognostic marker for patients with ESCC, who received neoadjuvant chemotherapy followed by surgery. 26323930 10 65 dep = 1624:1624 arg1 0.299-0.944 1609:1619 0.299-0.944 1609:1619 0.299-0.944 1609:1619 Multivariate analysis showed that combination of MUC13/MUC20 expression was an independent prognostic factor (hazard ratios = 0.531, 95% confidence interval: 0.299-0.944, P = 0.031). 26323930 10 65 dep = 1624:1624 arg1 0.531 1577:1581 hazard ratios = 0.531 1561:1581 hazard ratios = 0.531 1561:1581 Multivariate analysis showed that combination of MUC13/MUC20 expression was an independent prognostic factor (hazard ratios = 0.531, 95% confidence interval: 0.299-0.944, P = 0.031). 26323930 10 65 dep = 1624:1624 arg1 % 1586:1586 95% 1584:1586 95% confidence interval 1584:1606 Multivariate analysis showed that combination of MUC13/MUC20 expression was an independent prognostic factor (hazard ratios = 0.531, 95% confidence interval: 0.299-0.944, P = 0.031). 26323930 5 66 theme long-term 864:872 arg1 survival 874:881 long-term survival 864:881 long-term survival 864:881 We analyzed the correlations between MUC13 or MUC20 expression and long-term survival of these patients. 26323930 1 67 theme weight 175:180 arg1 Mucin 118:122 BACKGROUND Mucin 13 107:125 BACKGROUND Mucin 13 (MUC13) 107:133 BACKGROUND Mucin 13 (MUC13) and Mucin 20 (MUC20) are high molecular weight transmembrane O-linked glycoprotein secreted by epithelium and are widely overexpressed in epithelial tumor cells. 26323930 1 67 theme weight 175:180 arg1 Mucin 139:143 Mucin 20 139:146 Mucin 20 (MUC20) 139:154 BACKGROUND Mucin 13 (MUC13) and Mucin 20 (MUC20) are high molecular weight transmembrane O-linked glycoprotein secreted by epithelium and are widely overexpressed in epithelial tumor cells. 26323930 1 67 theme weight 175:180 arg1 glycoprotein 205:216 high molecular weight transmembrane O-linked glycoprotein 160:216 high molecular weight transmembrane O-linked glycoprotein secreted by epithelium 160:239 BACKGROUND Mucin 13 (MUC13) and Mucin 20 (MUC20) are high molecular weight transmembrane O-linked glycoprotein secreted by epithelium and are widely overexpressed in epithelial tumor cells. 26323930 2 68 theme esophageal 518:527 arg1 ESCC 554:557 ESCC 554:557 ESCC 554:557 Previously, it has been reported that MUC13 and MUC20 were prognostic molecular biomarkers of some epithelial tumors, but few has studied the relations between MUC13 or MUC20 expression and the prognosis of patients with esophageal squamous cell carcinoma (ESCC). 26323930 2 68 theme esophageal 518:527 arg1 carcinoma 543:551 esophageal squamous cell carcinoma 518:551 esophageal squamous cell carcinoma (ESCC) 518:558 Previously, it has been reported that MUC13 and MUC20 were prognostic molecular biomarkers of some epithelial tumors, but few has studied the relations between MUC13 or MUC20 expression and the prognosis of patients with esophageal squamous cell carcinoma (ESCC). 26323930 11 69 theme prognostic 1701:1710 arg1 combination 1647:1657 A combination 1645:1657 A combination of MUC13/MUC20 expression 1645:1683 CONCLUSION A combination of MUC13/MUC20 expression was a potential prognostic marker for patients with ESCC, who received neoadjuvant chemotherapy followed by surgery. 26323930 11 69 theme prognostic 1701:1710 arg1 marker 1712:1717 a potential prognostic marker 1689:1717 a potential prognostic marker for patients with ESCC, who received neoadjuvant chemotherapy followed by surgery 1689:1799 CONCLUSION A combination of MUC13/MUC20 expression was a potential prognostic marker for patients with ESCC, who received neoadjuvant chemotherapy followed by surgery. 26323930 1 70 theme transmembrane 182:194 arg1 Mucin 118:122 BACKGROUND Mucin 13 107:125 BACKGROUND Mucin 13 (MUC13) 107:133 BACKGROUND Mucin 13 (MUC13) and Mucin 20 (MUC20) are high molecular weight transmembrane O-linked glycoprotein secreted by epithelium and are widely overexpressed in epithelial tumor cells. 26323930 1 70 theme transmembrane 182:194 arg1 Mucin 139:143 Mucin 20 139:146 Mucin 20 (MUC20) 139:154 BACKGROUND Mucin 13 (MUC13) and Mucin 20 (MUC20) are high molecular weight transmembrane O-linked glycoprotein secreted by epithelium and are widely overexpressed in epithelial tumor cells. 26323930 1 70 theme transmembrane 182:194 arg1 glycoprotein 205:216 high molecular weight transmembrane O-linked glycoprotein 160:216 high molecular weight transmembrane O-linked glycoprotein secreted by epithelium 160:239 BACKGROUND Mucin 13 (MUC13) and Mucin 20 (MUC20) are high molecular weight transmembrane O-linked glycoprotein secreted by epithelium and are widely overexpressed in epithelial tumor cells. 26323930 0 71 theme Mucin 59:63 arg1 expression 4:13 expression 4:13 expression 4:13 The expression and prognostic significance of Mucin 13 and Mucin 20 in esophageal squamous cell carcinoma. 26323930 0 71 theme Mucin 59:63 arg1 significance 30:41 prognostic significance 19:41 prognostic significance 19:41 The expression and prognostic significance of Mucin 13 and Mucin 20 in esophageal squamous cell carcinoma. 26323930 1 72 theme molecular 165:173 arg1 weight 175:180 high molecular weight 160:180 high molecular weight transmembrane O-linked glycoprotein secreted by epithelium 160:239 BACKGROUND Mucin 13 (MUC13) and Mucin 20 (MUC20) are high molecular weight transmembrane O-linked glycoprotein secreted by epithelium and are widely overexpressed in epithelial tumor cells. 26323930 0 73 dep expression 4:13 arg1 The 0:2 The 0:2 The 0:2 The expression and prognostic significance of Mucin 13 and Mucin 20 in esophageal squamous cell carcinoma. 26323930 9 74 theme MUC13/low 1382:1390 arg1 expression 1398:1407 high MUC13/low MUC20 expression 1377:1407 high MUC13/low MUC20 expression 1377:1407 When combining expression of MUC13 with MUC20, we found that the median survival time of patients with low MUC13/high MUC20 expression was significantly shorter than that of patients with high MUC13/low MUC20 expression (27.7 months vs. 59.5 months, P = 0.021). 26323930 4 75 theme MATERIALS 615:623 arg1 Immunohistochemistry 637:656 MATERIALS AND METHODS Immunohistochemistry 615:656 MATERIALS AND METHODS Immunohistochemistry 615:656 MATERIALS AND METHODS Immunohistochemistry was used to detect the expressions of MUC13 and MUC20 in 186 patients with ESCC who received neoadjuvant chemotherapy followed by surgery. 26323930 2 76 with patients 504:511 arg1 ESCC 554:557 ESCC 554:557 ESCC 554:557 Previously, it has been reported that MUC13 and MUC20 were prognostic molecular biomarkers of some epithelial tumors, but few has studied the relations between MUC13 or MUC20 expression and the prognosis of patients with esophageal squamous cell carcinoma (ESCC). 26323930 2 76 with patients 504:511 arg1 carcinoma 543:551 esophageal squamous cell carcinoma 518:551 esophageal squamous cell carcinoma (ESCC) 518:558 Previously, it has been reported that MUC13 and MUC20 were prognostic molecular biomarkers of some epithelial tumors, but few has studied the relations between MUC13 or MUC20 expression and the prognosis of patients with esophageal squamous cell carcinoma (ESCC). 26323930 1 77 theme O-linked 196:203 arg1 Mucin 118:122 BACKGROUND Mucin 13 107:125 BACKGROUND Mucin 13 (MUC13) 107:133 BACKGROUND Mucin 13 (MUC13) and Mucin 20 (MUC20) are high molecular weight transmembrane O-linked glycoprotein secreted by epithelium and are widely overexpressed in epithelial tumor cells. 26323930 1 77 theme O-linked 196:203 arg1 Mucin 139:143 Mucin 20 139:146 Mucin 20 (MUC20) 139:154 BACKGROUND Mucin 13 (MUC13) and Mucin 20 (MUC20) are high molecular weight transmembrane O-linked glycoprotein secreted by epithelium and are widely overexpressed in epithelial tumor cells. 26323930 1 77 theme O-linked 196:203 arg1 glycoprotein 205:216 high molecular weight transmembrane O-linked glycoprotein 160:216 high molecular weight transmembrane O-linked glycoprotein secreted by epithelium 160:239 BACKGROUND Mucin 13 (MUC13) and Mucin 20 (MUC20) are high molecular weight transmembrane O-linked glycoprotein secreted by epithelium and are widely overexpressed in epithelial tumor cells. 26323930 9 78 theme MUC13/high 1296:1305 arg1 expression 1313:1322 low MUC13/high MUC20 expression 1292:1322 low MUC13/high MUC20 expression 1292:1322 When combining expression of MUC13 with MUC20, we found that the median survival time of patients with low MUC13/high MUC20 expression was significantly shorter than that of patients with high MUC13/low MUC20 expression (27.7 months vs. 59.5 months, P = 0.021). 26323930 10 79 theme prognostic 1542:1551 arg1 combination 1485:1495 combination 1485:1495 combination of MUC13/MUC20 expression 1485:1521 Multivariate analysis showed that combination of MUC13/MUC20 expression was an independent prognostic factor (hazard ratios = 0.531, 95% confidence interval: 0.299-0.944, P = 0.031). 26323930 10 79 theme prognostic 1542:1551 arg1 factor 1553:1558 an independent prognostic factor 1527:1558 an independent prognostic factor 1527:1558 Multivariate analysis showed that combination of MUC13/MUC20 expression was an independent prognostic factor (hazard ratios = 0.531, 95% confidence interval: 0.299-0.944, P = 0.031). 26323930 9 80 theme patients 1278:1285 arg1 shorter 1342:1348 shorter 1342:1348 shorter 1342:1348 When combining expression of MUC13 with MUC20, we found that the median survival time of patients with low MUC13/high MUC20 expression was significantly shorter than that of patients with high MUC13/low MUC20 expression (27.7 months vs. 59.5 months, P = 0.021). 26323930 9 80 theme patients 1278:1285 arg1 time 1270:1273 the median survival time 1250:1273 the median survival time of patients with low MUC13/high MUC20 expression 1250:1322 When combining expression of MUC13 with MUC20, we found that the median survival time of patients with low MUC13/high MUC20 expression was significantly shorter than that of patients with high MUC13/low MUC20 expression (27.7 months vs. 59.5 months, P = 0.021). 28710419 0 0 theme Cnidaria-Symbiodinium 94:114 arg1 endosymbiosis 116:128 Cnidaria-Symbiodinium endosymbiosis 94:128 Cnidaria-Symbiodinium endosymbiosis 94:128 Generation of clade- and symbiont-specific antibodies to characterize marker molecules during Cnidaria-Symbiodinium endosymbiosis. 28710419 3 1 theme molecular 369:377 arg1 interaction 379:389 the molecular interaction 365:389 the molecular interaction 365:389 However, the complexity of the molecular interaction has prevented the establishment of a mechanistic explanation of cellular regulation in this mutualistic symbiosis. 28710419 5 2 theme SGCs 717:720 arg1 cells 699:703 whole cells 693:703 whole cells of isolated SGCs 693:720 Because the endosymbiotic association occurs in the symbiotic gastrodermal cells (SGCs), whole cells of isolated SGCs were used as an antigen to generate monoclonal antibodies (mAb) to screen possible molecular candidates of symbiotic markers. 28710419 5 2 theme SGCs 717:720 arg1 antigen 738:744 an antigen to generate monoclonal antibodies (mAb) 735:784 an antigen to generate monoclonal antibodies (mAb) 735:784 Because the endosymbiotic association occurs in the symbiotic gastrodermal cells (SGCs), whole cells of isolated SGCs were used as an antigen to generate monoclonal antibodies (mAb) to screen possible molecular candidates of symbiotic markers. 28710419 8 3 theme cnidaria-Symbiodinium 1561:1581 arg1 endosymbiosis 1583:1595 cnidaria-Symbiodinium endosymbiosis 1561:1595 cnidaria-Symbiodinium endosymbiosis 1561:1595 Consequently, the 2-6F mAb can be used to detect the symbiotic state of corals and investigate the complex molecular interactions in cnidaria-Symbiodinium endosymbiosis. 28710419 3 4 theme interaction 379:389 arg1 complexity 351:360 the complexity 347:360 the complexity of the molecular interaction 347:389 However, the complexity of the molecular interaction has prevented the establishment of a mechanistic explanation of cellular regulation in this mutualistic symbiosis. 28710419 4 5 theme symbiotic 586:594 arg1 status 596:601 the symbiotic status 582:601 the symbiotic status 582:601 To date, no marker molecules have been identified to specifically represent the symbiotic status. 28710419 7 6 dep N-glycosidase 1237:1249 arg1 F. 1251:1252 F. 1251:1252 F. 1251:1252 The expression levels of 2-6F mAb-recognized proteins are highly correlated with the symbiotic status, and these proteins were characterized as N-linked glycoproteins via treatment with peptide N-glycosidase F. Furthermore, their glycan moieties were markedly different from those of free-living Symbiodinium, potentially suggesting host regulation of post-translational modification. 28710419 7 7 with treatment 1214:1222 arg1 N-glycosidase 1237:1249 peptide N-glycosidase F. 1229:1252 peptide N-glycosidase F. 1229:1252 The expression levels of 2-6F mAb-recognized proteins are highly correlated with the symbiotic status, and these proteins were characterized as N-linked glycoproteins via treatment with peptide N-glycosidase F. Furthermore, their glycan moieties were markedly different from those of free-living Symbiodinium, potentially suggesting host regulation of post-translational modification. 28710419 2 8 from Changes 237:243 arg1 molecules 248:256 molecules 248:256 molecules 248:256 Changes in molecules have been identified during the process of cnidaria-Symbiodinium endosymbiosis. 28710419 7 9 theme N-linked 1187:1194 arg1 glycoproteins 1196:1208 N-linked glycoproteins 1187:1208 N-linked glycoproteins 1187:1208 The expression levels of 2-6F mAb-recognized proteins are highly correlated with the symbiotic status, and these proteins were characterized as N-linked glycoproteins via treatment with peptide N-glycosidase F. Furthermore, their glycan moieties were markedly different from those of free-living Symbiodinium, potentially suggesting host regulation of post-translational modification. 28710419 7 9 theme N-linked 1187:1194 arg1 proteins 1156:1163 these proteins 1150:1163 these proteins 1150:1163 The expression levels of 2-6F mAb-recognized proteins are highly correlated with the symbiotic status, and these proteins were characterized as N-linked glycoproteins via treatment with peptide N-glycosidase F. Furthermore, their glycan moieties were markedly different from those of free-living Symbiodinium, potentially suggesting host regulation of post-translational modification. 28710419 8 10 theme molecular 1535:1543 arg1 interactions 1545:1556 the complex molecular interactions 1523:1556 the complex molecular interactions in cnidaria-Symbiodinium endosymbiosis 1523:1595 Consequently, the 2-6F mAb can be used to detect the symbiotic state of corals and investigate the complex molecular interactions in cnidaria-Symbiodinium endosymbiosis. 28710419 5 11 used used 727:730 arg2 antigen 738:744 an antigen to generate monoclonal antibodies (mAb) 735:784 an antigen to generate monoclonal antibodies (mAb) 735:784 Because the endosymbiotic association occurs in the symbiotic gastrodermal cells (SGCs), whole cells of isolated SGCs were used as an antigen to generate monoclonal antibodies (mAb) to screen possible molecular candidates of symbiotic markers. 28710419 5 11 used used 727:730 arg2 cells 699:703 whole cells 693:703 whole cells of isolated SGCs 693:720 Because the endosymbiotic association occurs in the symbiotic gastrodermal cells (SGCs), whole cells of isolated SGCs were used as an antigen to generate monoclonal antibodies (mAb) to screen possible molecular candidates of symbiotic markers. 28710419 6 12 theme symbiotic 954:962 arg1 Symbiodinium 964:975 clade C symbiotic Symbiodinium 946:975 clade C symbiotic Symbiodinium but not its free-living counterpart or other Symbiodinium clades 946:1040 The results showed that one of the generated monoclonal antibodies, 2-6F, specifically recognized clade C symbiotic Symbiodinium but not its free-living counterpart or other Symbiodinium clades. 28710419 6 13 theme C 952:952 arg1 Symbiodinium 964:975 clade C symbiotic Symbiodinium 946:975 clade C symbiotic Symbiodinium but not its free-living counterpart or other Symbiodinium clades 946:1040 The results showed that one of the generated monoclonal antibodies, 2-6F, specifically recognized clade C symbiotic Symbiodinium but not its free-living counterpart or other Symbiodinium clades. 28710419 5 14 theme whole 693:697 arg1 cells 699:703 whole cells 693:703 whole cells of isolated SGCs 693:720 Because the endosymbiotic association occurs in the symbiotic gastrodermal cells (SGCs), whole cells of isolated SGCs were used as an antigen to generate monoclonal antibodies (mAb) to screen possible molecular candidates of symbiotic markers. 28710419 5 14 theme whole 693:697 arg1 antigen 738:744 an antigen to generate monoclonal antibodies (mAb) 735:784 an antigen to generate monoclonal antibodies (mAb) 735:784 Because the endosymbiotic association occurs in the symbiotic gastrodermal cells (SGCs), whole cells of isolated SGCs were used as an antigen to generate monoclonal antibodies (mAb) to screen possible molecular candidates of symbiotic markers. 28710419 5 15 theme possible 796:803 arg1 candidates 815:824 possible molecular candidates 796:824 possible molecular candidates of symbiotic markers 796:845 Because the endosymbiotic association occurs in the symbiotic gastrodermal cells (SGCs), whole cells of isolated SGCs were used as an antigen to generate monoclonal antibodies (mAb) to screen possible molecular candidates of symbiotic markers. 28710419 6 16 theme clade 946:950 arg1 Symbiodinium 964:975 clade C symbiotic Symbiodinium 946:975 clade C symbiotic Symbiodinium but not its free-living counterpart or other Symbiodinium clades 946:1040 The results showed that one of the generated monoclonal antibodies, 2-6F, specifically recognized clade C symbiotic Symbiodinium but not its free-living counterpart or other Symbiodinium clades. 28710419 5 17 theme markers 839:845 arg1 candidates 815:824 possible molecular candidates 796:824 possible molecular candidates of symbiotic markers 796:845 Because the endosymbiotic association occurs in the symbiotic gastrodermal cells (SGCs), whole cells of isolated SGCs were used as an antigen to generate monoclonal antibodies (mAb) to screen possible molecular candidates of symbiotic markers. 28710419 2 18 theme endosymbiosis 323:335 arg1 process 290:296 the process 286:296 the process of cnidaria-Symbiodinium endosymbiosis 286:335 Changes in molecules have been identified during the process of cnidaria-Symbiodinium endosymbiosis. 28710419 5 19 theme symbiotic 829:837 arg1 markers 839:845 symbiotic markers 829:845 symbiotic markers 829:845 Because the endosymbiotic association occurs in the symbiotic gastrodermal cells (SGCs), whole cells of isolated SGCs were used as an antigen to generate monoclonal antibodies (mAb) to screen possible molecular candidates of symbiotic markers. 28710419 7 20 theme modification 1414:1425 arg1 regulation 1381:1390 host regulation 1376:1390 host regulation of post-translational modification 1376:1425 The expression levels of 2-6F mAb-recognized proteins are highly correlated with the symbiotic status, and these proteins were characterized as N-linked glycoproteins via treatment with peptide N-glycosidase F. Furthermore, their glycan moieties were markedly different from those of free-living Symbiodinium, potentially suggesting host regulation of post-translational modification. 28710419 5 21 theme symbiotic 656:664 arg1 SGCs 686:689 SGCs 686:689 SGCs 686:689 Because the endosymbiotic association occurs in the symbiotic gastrodermal cells (SGCs), whole cells of isolated SGCs were used as an antigen to generate monoclonal antibodies (mAb) to screen possible molecular candidates of symbiotic markers. 28710419 5 21 theme symbiotic 656:664 arg1 cells 679:683 the symbiotic gastrodermal cells 652:683 the symbiotic gastrodermal cells (SGCs) 652:690 Because the endosymbiotic association occurs in the symbiotic gastrodermal cells (SGCs), whole cells of isolated SGCs were used as an antigen to generate monoclonal antibodies (mAb) to screen possible molecular candidates of symbiotic markers. 28710419 8 22 theme symbiotic 1481:1489 arg1 state 1491:1495 the symbiotic state 1477:1495 the symbiotic state of corals 1477:1505 Consequently, the 2-6F mAb can be used to detect the symbiotic state of corals and investigate the complex molecular interactions in cnidaria-Symbiodinium endosymbiosis. 28710419 1 23 theme coral 224:228 arg1 reefs 230:234 coral reefs 224:234 coral reefs 224:234 The endosymbiosis between cnidarians and dinoflagellates is responsible for the formation of coral reefs. 28710419 3 24 theme cellular 455:462 arg1 regulation 464:473 cellular regulation 455:473 cellular regulation 455:473 However, the complexity of the molecular interaction has prevented the establishment of a mechanistic explanation of cellular regulation in this mutualistic symbiosis. 28710419 5 25 theme isolated 708:715 arg1 SGCs 717:720 isolated SGCs 708:720 isolated SGCs 708:720 Because the endosymbiotic association occurs in the symbiotic gastrodermal cells (SGCs), whole cells of isolated SGCs were used as an antigen to generate monoclonal antibodies (mAb) to screen possible molecular candidates of symbiotic markers. 28710419 5 26 theme gastrodermal 666:677 arg1 SGCs 686:689 SGCs 686:689 SGCs 686:689 Because the endosymbiotic association occurs in the symbiotic gastrodermal cells (SGCs), whole cells of isolated SGCs were used as an antigen to generate monoclonal antibodies (mAb) to screen possible molecular candidates of symbiotic markers. 28710419 5 26 theme gastrodermal 666:677 arg1 cells 679:683 the symbiotic gastrodermal cells 652:683 the symbiotic gastrodermal cells (SGCs) 652:690 Because the endosymbiotic association occurs in the symbiotic gastrodermal cells (SGCs), whole cells of isolated SGCs were used as an antigen to generate monoclonal antibodies (mAb) to screen possible molecular candidates of symbiotic markers. 28710419 1 27 theme reefs 230:234 arg1 formation 211:219 the formation 207:219 the formation of coral reefs 207:234 The endosymbiosis between cnidarians and dinoflagellates is responsible for the formation of coral reefs. 28710419 3 28 theme mechanistic 428:438 arg1 explanation 440:450 a mechanistic explanation 426:450 a mechanistic explanation of cellular regulation 426:473 However, the complexity of the molecular interaction has prevented the establishment of a mechanistic explanation of cellular regulation in this mutualistic symbiosis. 28710419 5 29 theme monoclonal 758:767 arg1 antibodies 769:778 monoclonal antibodies 758:778 monoclonal antibodies (mAb) 758:784 Because the endosymbiotic association occurs in the symbiotic gastrodermal cells (SGCs), whole cells of isolated SGCs were used as an antigen to generate monoclonal antibodies (mAb) to screen possible molecular candidates of symbiotic markers. 28710419 5 29 theme monoclonal 758:767 arg1 mAb 781:783 mAb 781:783 mAb 781:783 Because the endosymbiotic association occurs in the symbiotic gastrodermal cells (SGCs), whole cells of isolated SGCs were used as an antigen to generate monoclonal antibodies (mAb) to screen possible molecular candidates of symbiotic markers. 28710419 8 30 from interactions 1545:1556 arg1 endosymbiosis 1583:1595 cnidaria-Symbiodinium endosymbiosis 1561:1595 cnidaria-Symbiodinium endosymbiosis 1561:1595 Consequently, the 2-6F mAb can be used to detect the symbiotic state of corals and investigate the complex molecular interactions in cnidaria-Symbiodinium endosymbiosis. 28710419 7 31 link N-linked 1187:1194 arg1 glycoproteins 1196:1208 N-linked glycoproteins 1187:1208 N-linked glycoproteins 1187:1208 The expression levels of 2-6F mAb-recognized proteins are highly correlated with the symbiotic status, and these proteins were characterized as N-linked glycoproteins via treatment with peptide N-glycosidase F. Furthermore, their glycan moieties were markedly different from those of free-living Symbiodinium, potentially suggesting host regulation of post-translational modification. 28710419 7 31 link N-linked 1187:1194 arg1 proteins 1156:1163 these proteins 1150:1163 these proteins 1150:1163 The expression levels of 2-6F mAb-recognized proteins are highly correlated with the symbiotic status, and these proteins were characterized as N-linked glycoproteins via treatment with peptide N-glycosidase F. Furthermore, their glycan moieties were markedly different from those of free-living Symbiodinium, potentially suggesting host regulation of post-translational modification. 28710419 3 32 theme explanation 440:450 arg1 establishment 409:421 the establishment 405:421 the establishment of a mechanistic explanation of cellular regulation in this mutualistic symbiosis 405:503 However, the complexity of the molecular interaction has prevented the establishment of a mechanistic explanation of cellular regulation in this mutualistic symbiosis. 28710419 0 33 theme antibodies 43:52 arg1 Generation 0:9 Generation 0:9 Generation of clade- and symbiont-specific antibodies 0:52 Generation of clade- and symbiont-specific antibodies to characterize marker molecules during Cnidaria-Symbiodinium endosymbiosis. 28710419 6 34 theme Symbiodinium 1022:1033 arg1 clades 1035:1040 other Symbiodinium clades 1016:1040 other Symbiodinium clades 1016:1040 The results showed that one of the generated monoclonal antibodies, 2-6F, specifically recognized clade C symbiotic Symbiodinium but not its free-living counterpart or other Symbiodinium clades. 28710419 3 35 from establishment 409:421 arg1 symbiosis 495:503 this mutualistic symbiosis 478:503 this mutualistic symbiosis 478:503 However, the complexity of the molecular interaction has prevented the establishment of a mechanistic explanation of cellular regulation in this mutualistic symbiosis. 28710419 8 36 used used 1462:1465 arg2 mAb 1451:1453 the 2-6F mAb 1442:1453 the 2-6F mAb 1442:1453 Consequently, the 2-6F mAb can be used to detect the symbiotic state of corals and investigate the complex molecular interactions in cnidaria-Symbiodinium endosymbiosis. 28710419 7 37 gly glycoproteins 1196:1208 arg1 glycoproteins 1196:1208 N-linked glycoproteins 1187:1208 N-linked glycoproteins 1187:1208 The expression levels of 2-6F mAb-recognized proteins are highly correlated with the symbiotic status, and these proteins were characterized as N-linked glycoproteins via treatment with peptide N-glycosidase F. Furthermore, their glycan moieties were markedly different from those of free-living Symbiodinium, potentially suggesting host regulation of post-translational modification. 28710419 7 37 gly glycoproteins 1196:1208 arg1 proteins 1156:1163 these proteins 1150:1163 these proteins 1150:1163 The expression levels of 2-6F mAb-recognized proteins are highly correlated with the symbiotic status, and these proteins were characterized as N-linked glycoproteins via treatment with peptide N-glycosidase F. Furthermore, their glycan moieties were markedly different from those of free-living Symbiodinium, potentially suggesting host regulation of post-translational modification. 28710419 0 38 theme symbiont-specific 25:41 arg1 antibodies 43:52 clade- and symbiont-specific antibodies 14:52 clade- and symbiont-specific antibodies 14:52 Generation of clade- and symbiont-specific antibodies to characterize marker molecules during Cnidaria-Symbiodinium endosymbiosis. 28710419 6 39 theme other 1016:1020 arg1 clades 1035:1040 other Symbiodinium clades 1016:1040 other Symbiodinium clades 1016:1040 The results showed that one of the generated monoclonal antibodies, 2-6F, specifically recognized clade C symbiotic Symbiodinium but not its free-living counterpart or other Symbiodinium clades. 28710419 3 40 theme mutualistic 483:493 arg1 symbiosis 495:503 this mutualistic symbiosis 478:503 this mutualistic symbiosis 478:503 However, the complexity of the molecular interaction has prevented the establishment of a mechanistic explanation of cellular regulation in this mutualistic symbiosis. 28710419 8 41 theme corals 1500:1505 arg1 state 1491:1495 the symbiotic state 1477:1495 the symbiotic state of corals 1477:1505 Consequently, the 2-6F mAb can be used to detect the symbiotic state of corals and investigate the complex molecular interactions in cnidaria-Symbiodinium endosymbiosis. 28710419 5 42 theme endosymbiotic 616:628 arg1 association 630:640 the endosymbiotic association 612:640 the endosymbiotic association 612:640 Because the endosymbiotic association occurs in the symbiotic gastrodermal cells (SGCs), whole cells of isolated SGCs were used as an antigen to generate monoclonal antibodies (mAb) to screen possible molecular candidates of symbiotic markers. 28710419 3 43 theme regulation 464:473 arg1 explanation 440:450 a mechanistic explanation 426:450 a mechanistic explanation of cellular regulation 426:473 However, the complexity of the molecular interaction has prevented the establishment of a mechanistic explanation of cellular regulation in this mutualistic symbiosis. 28710419 4 44 theme marker 518:523 arg1 molecules 525:533 no marker molecules 515:533 no marker molecules 515:533 To date, no marker molecules have been identified to specifically represent the symbiotic status. 28710419 7 45 theme peptide 1229:1235 arg1 N-glycosidase 1237:1249 peptide N-glycosidase F. 1229:1252 peptide N-glycosidase F. 1229:1252 The expression levels of 2-6F mAb-recognized proteins are highly correlated with the symbiotic status, and these proteins were characterized as N-linked glycoproteins via treatment with peptide N-glycosidase F. Furthermore, their glycan moieties were markedly different from those of free-living Symbiodinium, potentially suggesting host regulation of post-translational modification. 28710419 7 46 theme symbiotic 1128:1136 arg1 status 1138:1143 the symbiotic status 1124:1143 the symbiotic status 1124:1143 The expression levels of 2-6F mAb-recognized proteins are highly correlated with the symbiotic status, and these proteins were characterized as N-linked glycoproteins via treatment with peptide N-glycosidase F. Furthermore, their glycan moieties were markedly different from those of free-living Symbiodinium, potentially suggesting host regulation of post-translational modification. 28710419 6 47 theme antibodies 904:913 arg1 2-6F 916:919 2-6F 916:919 2-6F 916:919 The results showed that one of the generated monoclonal antibodies, 2-6F, specifically recognized clade C symbiotic Symbiodinium but not its free-living counterpart or other Symbiodinium clades. 28710419 6 47 theme antibodies 904:913 arg1 antibodies 904:913 the generated monoclonal antibodies 879:913 the generated monoclonal antibodies 879:913 The results showed that one of the generated monoclonal antibodies, 2-6F, specifically recognized clade C symbiotic Symbiodinium but not its free-living counterpart or other Symbiodinium clades. 28710419 6 47 theme antibodies 904:913 arg1 one 872:874 one 872:874 one 872:874 The results showed that one of the generated monoclonal antibodies, 2-6F, specifically recognized clade C symbiotic Symbiodinium but not its free-living counterpart or other Symbiodinium clades. 28710419 7 48 from those 1318:1322 arg1 different 1303:1311 different 1303:1311 different 1303:1311 The expression levels of 2-6F mAb-recognized proteins are highly correlated with the symbiotic status, and these proteins were characterized as N-linked glycoproteins via treatment with peptide N-glycosidase F. Furthermore, their glycan moieties were markedly different from those of free-living Symbiodinium, potentially suggesting host regulation of post-translational modification. 28710419 7 49 theme mAb-recognized 1073:1086 arg1 proteins 1088:1095 2-6F mAb-recognized proteins 1068:1095 2-6F mAb-recognized proteins 1068:1095 The expression levels of 2-6F mAb-recognized proteins are highly correlated with the symbiotic status, and these proteins were characterized as N-linked glycoproteins via treatment with peptide N-glycosidase F. Furthermore, their glycan moieties were markedly different from those of free-living Symbiodinium, potentially suggesting host regulation of post-translational modification. 28710419 7 50 theme post-translational 1395:1412 arg1 modification 1414:1425 post-translational modification 1395:1425 post-translational modification 1395:1425 The expression levels of 2-6F mAb-recognized proteins are highly correlated with the symbiotic status, and these proteins were characterized as N-linked glycoproteins via treatment with peptide N-glycosidase F. Furthermore, their glycan moieties were markedly different from those of free-living Symbiodinium, potentially suggesting host regulation of post-translational modification. 28710419 6 51 theme free-living 989:999 arg1 counterpart 1001:1011 its free-living counterpart 985:1011 its free-living counterpart 985:1011 The results showed that one of the generated monoclonal antibodies, 2-6F, specifically recognized clade C symbiotic Symbiodinium but not its free-living counterpart or other Symbiodinium clades. 28710419 6 52 theme monoclonal 893:902 arg1 antibodies 904:913 the generated monoclonal antibodies 879:913 the generated monoclonal antibodies 879:913 The results showed that one of the generated monoclonal antibodies, 2-6F, specifically recognized clade C symbiotic Symbiodinium but not its free-living counterpart or other Symbiodinium clades. 28710419 2 53 theme cnidaria-Symbiodinium 301:321 arg1 endosymbiosis 323:335 cnidaria-Symbiodinium endosymbiosis 301:335 cnidaria-Symbiodinium endosymbiosis 301:335 Changes in molecules have been identified during the process of cnidaria-Symbiodinium endosymbiosis. 28710419 7 54 theme proteins 1088:1095 arg1 levels 1058:1063 The expression levels 1043:1063 The expression levels of 2-6F mAb-recognized proteins 1043:1095 The expression levels of 2-6F mAb-recognized proteins are highly correlated with the symbiotic status, and these proteins were characterized as N-linked glycoproteins via treatment with peptide N-glycosidase F. Furthermore, their glycan moieties were markedly different from those of free-living Symbiodinium, potentially suggesting host regulation of post-translational modification. 28710419 7 55 theme host 1376:1379 arg1 regulation 1381:1390 host regulation 1376:1390 host regulation of post-translational modification 1376:1425 The expression levels of 2-6F mAb-recognized proteins are highly correlated with the symbiotic status, and these proteins were characterized as N-linked glycoproteins via treatment with peptide N-glycosidase F. Furthermore, their glycan moieties were markedly different from those of free-living Symbiodinium, potentially suggesting host regulation of post-translational modification. 28710419 6 56 theme generated 883:891 arg1 antibodies 904:913 the generated monoclonal antibodies 879:913 the generated monoclonal antibodies 879:913 The results showed that one of the generated monoclonal antibodies, 2-6F, specifically recognized clade C symbiotic Symbiodinium but not its free-living counterpart or other Symbiodinium clades. 28710419 8 57 theme complex 1527:1533 arg1 interactions 1545:1556 the complex molecular interactions 1523:1556 the complex molecular interactions in cnidaria-Symbiodinium endosymbiosis 1523:1595 Consequently, the 2-6F mAb can be used to detect the symbiotic state of corals and investigate the complex molecular interactions in cnidaria-Symbiodinium endosymbiosis. 28710419 5 58 theme molecular 805:813 arg1 candidates 815:824 possible molecular candidates 796:824 possible molecular candidates of symbiotic markers 796:845 Because the endosymbiotic association occurs in the symbiotic gastrodermal cells (SGCs), whole cells of isolated SGCs were used as an antigen to generate monoclonal antibodies (mAb) to screen possible molecular candidates of symbiotic markers. 28710419 7 59 theme 2-6F 1068:1071 arg1 proteins 1088:1095 2-6F mAb-recognized proteins 1068:1095 2-6F mAb-recognized proteins 1068:1095 The expression levels of 2-6F mAb-recognized proteins are highly correlated with the symbiotic status, and these proteins were characterized as N-linked glycoproteins via treatment with peptide N-glycosidase F. Furthermore, their glycan moieties were markedly different from those of free-living Symbiodinium, potentially suggesting host regulation of post-translational modification. 28710419 8 60 theme 2-6F 1446:1449 arg1 mAb 1451:1453 the 2-6F mAb 1442:1453 the 2-6F mAb 1442:1453 Consequently, the 2-6F mAb can be used to detect the symbiotic state of corals and investigate the complex molecular interactions in cnidaria-Symbiodinium endosymbiosis. 28710419 7 61 theme free-living 1327:1337 arg1 Symbiodinium 1339:1350 free-living Symbiodinium 1327:1350 free-living Symbiodinium 1327:1350 The expression levels of 2-6F mAb-recognized proteins are highly correlated with the symbiotic status, and these proteins were characterized as N-linked glycoproteins via treatment with peptide N-glycosidase F. Furthermore, their glycan moieties were markedly different from those of free-living Symbiodinium, potentially suggesting host regulation of post-translational modification. 28710419 0 62 theme marker 70:75 arg1 molecules 77:85 marker molecules 70:85 marker molecules 70:85 Generation of clade- and symbiont-specific antibodies to characterize marker molecules during Cnidaria-Symbiodinium endosymbiosis. 28710419 0 63 theme clade- 14:19 arg1 antibodies 43:52 clade- and symbiont-specific antibodies 14:52 clade- and symbiont-specific antibodies 14:52 Generation of clade- and symbiont-specific antibodies to characterize marker molecules during Cnidaria-Symbiodinium endosymbiosis. 28710419 7 64 theme expression 1047:1056 arg1 levels 1058:1063 The expression levels 1043:1063 The expression levels of 2-6F mAb-recognized proteins 1043:1095 The expression levels of 2-6F mAb-recognized proteins are highly correlated with the symbiotic status, and these proteins were characterized as N-linked glycoproteins via treatment with peptide N-glycosidase F. Furthermore, their glycan moieties were markedly different from those of free-living Symbiodinium, potentially suggesting host regulation of post-translational modification. 28710419 7 65 theme glycan 1273:1278 arg1 moieties 1280:1287 their glycan moieties 1267:1287 their glycan moieties 1267:1287 The expression levels of 2-6F mAb-recognized proteins are highly correlated with the symbiotic status, and these proteins were characterized as N-linked glycoproteins via treatment with peptide N-glycosidase F. Furthermore, their glycan moieties were markedly different from those of free-living Symbiodinium, potentially suggesting host regulation of post-translational modification. 27666430 7 0 theme matrix 1378:1383 arg1 proteins 1385:1392 pericellular matrix proteins 1365:1392 pericellular matrix proteins of the basement membranes 1365:1418 Consistent with other SIBLING-MMP pairs, the DSPP-MMP20 pair may play a role in the normal turnover of cell surface proteins and/or repair of pericellular matrix proteins of the basement membranes in the metabolically active duct epithelial system of the nephrons. 27666430 7 1 theme proteins 1339:1346 arg1 turnover 1314:1321 the normal turnover 1303:1321 the normal turnover of cell surface proteins 1303:1346 Consistent with other SIBLING-MMP pairs, the DSPP-MMP20 pair may play a role in the normal turnover of cell surface proteins and/or repair of pericellular matrix proteins of the basement membranes in the metabolically active duct epithelial system of the nephrons. 27666430 7 2 theme surface 1331:1337 arg1 proteins 1339:1346 cell surface proteins 1326:1346 cell surface proteins 1326:1346 Consistent with other SIBLING-MMP pairs, the DSPP-MMP20 pair may play a role in the normal turnover of cell surface proteins and/or repair of pericellular matrix proteins of the basement membranes in the metabolically active duct epithelial system of the nephrons. 27666430 6 3 theme renal 1210:1214 arg1 cells 1216:1220 mixed renal cells 1204:1220 mixed renal cells 1204:1220 Furthermore, MMP20 co-expressed with DSPP in the proximal, distal, and collecting tubules, and in mixed renal cells. 27666430 3 4 with osteopontin 651:661 arg1 members 601:607 specific members 592:607 specific members of the SIBLING family 592:629 Our earlier reports have shown the co-expression of three MMPs, MMP2, MMP3, and MMP9, with specific members of the SIBLING family: bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 27666430 1 5 theme active 239:244 arg1 cells 264:268 the metabolically active ductal epithelial cells 221:268 the metabolically active ductal epithelial cells of human salivary glands 221:293 We recently reported the expression of matrix metalloproteinase 20 (MMP20), hitherto thought to be tooth specific, in the metabolically active ductal epithelial cells of human salivary glands. 27666430 0 6 theme Monkey 87:92 arg1 Kidneys 94:100 Human and Monkey Kidneys 77:100 Human and Monkey Kidneys 77:100 Matrix Metalloproteinase 20 Co-expression With Dentin Sialophosphoprotein in Human and Monkey Kidneys. 27666430 5 7 theme distal 1057:1062 arg1 tubules 1064:1070 the proximal and distal tubules 1040:1070 the proximal and distal tubules 1040:1070 Our results show that MMP20 is expressed in all segments of the human and monkey nephron with marked intensity in the proximal and distal tubules, and was absent in the glomeruli. 27666430 4 8 theme kidney 816:821 arg1 sections 823:830 human and monkey kidney sections 799:830 human and monkey kidney sections 799:830 This study investigated the expression of MMP20 and verified its co-expression with DSPP in human and monkey kidney sections and human mixed renal cells by IHC, in situ proximity ligation assay, and immunofluorescence. 27666430 3 9 theme earlier 505:511 arg1 reports 513:519 Our earlier reports 501:519 Our earlier reports 501:519 Our earlier reports have shown the co-expression of three MMPs, MMP2, MMP3, and MMP9, with specific members of the SIBLING family: bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 27666430 1 10 theme ductal 246:251 arg1 cells 264:268 the metabolically active ductal epithelial cells 221:268 the metabolically active ductal epithelial cells of human salivary glands 221:293 We recently reported the expression of matrix metalloproteinase 20 (MMP20), hitherto thought to be tooth specific, in the metabolically active ductal epithelial cells of human salivary glands. 27666430 4 11 theme ligation 886:893 arg1 assay 895:899 in situ proximity ligation assay 868:899 in situ proximity ligation assay 868:899 This study investigated the expression of MMP20 and verified its co-expression with DSPP in human and monkey kidney sections and human mixed renal cells by IHC, in situ proximity ligation assay, and immunofluorescence. 27666430 5 12 theme proximal 1044:1051 arg1 tubules 1064:1070 the proximal and distal tubules 1040:1070 the proximal and distal tubules 1040:1070 Our results show that MMP20 is expressed in all segments of the human and monkey nephron with marked intensity in the proximal and distal tubules, and was absent in the glomeruli. 27666430 4 13 theme human 836:840 arg1 cells 854:858 human mixed renal cells 836:858 human mixed renal cells 836:858 This study investigated the expression of MMP20 and verified its co-expression with DSPP in human and monkey kidney sections and human mixed renal cells by IHC, in situ proximity ligation assay, and immunofluorescence. 27666430 7 14 with Consistent 1223:1232 arg1 pairs 1257:1261 other SIBLING-MMP pairs 1239:1261 other SIBLING-MMP pairs 1239:1261 Consistent with other SIBLING-MMP pairs, the DSPP-MMP20 pair may play a role in the normal turnover of cell surface proteins and/or repair of pericellular matrix proteins of the basement membranes in the metabolically active duct epithelial system of the nephrons. 27666430 1 15 theme epithelial 253:262 arg1 cells 264:268 the metabolically active ductal epithelial cells 221:268 the metabolically active ductal epithelial cells of human salivary glands 221:293 We recently reported the expression of matrix metalloproteinase 20 (MMP20), hitherto thought to be tooth specific, in the metabolically active ductal epithelial cells of human salivary glands. 27666430 4 16 theme proximity 876:884 arg1 assay 895:899 in situ proximity ligation assay 868:899 in situ proximity ligation assay 868:899 This study investigated the expression of MMP20 and verified its co-expression with DSPP in human and monkey kidney sections and human mixed renal cells by IHC, in situ proximity ligation assay, and immunofluorescence. 27666430 5 17 theme marked 1020:1025 arg1 intensity 1027:1035 marked intensity 1020:1035 marked intensity in the proximal and distal tubules 1020:1070 Our results show that MMP20 is expressed in all segments of the human and monkey nephron with marked intensity in the proximal and distal tubules, and was absent in the glomeruli. 27666430 7 18 theme pericellular 1365:1376 arg1 proteins 1385:1392 pericellular matrix proteins 1365:1392 pericellular matrix proteins of the basement membranes 1365:1418 Consistent with other SIBLING-MMP pairs, the DSPP-MMP20 pair may play a role in the normal turnover of cell surface proteins and/or repair of pericellular matrix proteins of the basement membranes in the metabolically active duct epithelial system of the nephrons. 27666430 7 19 theme duct 1448:1451 arg1 system 1464:1469 the metabolically active duct epithelial system 1423:1469 the metabolically active duct epithelial system of the nephrons 1423:1485 Consistent with other SIBLING-MMP pairs, the DSPP-MMP20 pair may play a role in the normal turnover of cell surface proteins and/or repair of pericellular matrix proteins of the basement membranes in the metabolically active duct epithelial system of the nephrons. 27666430 4 20 theme human 799:803 arg1 sections 823:830 human and monkey kidney sections 799:830 human and monkey kidney sections 799:830 This study investigated the expression of MMP20 and verified its co-expression with DSPP in human and monkey kidney sections and human mixed renal cells by IHC, in situ proximity ligation assay, and immunofluorescence. 27666430 6 21 theme mixed 1204:1208 arg1 cells 1216:1220 mixed renal cells 1204:1220 mixed renal cells 1204:1220 Furthermore, MMP20 co-expressed with DSPP in the proximal, distal, and collecting tubules, and in mixed renal cells. 27666430 7 22 from role 1295:1298 arg1 turnover 1314:1321 the normal turnover 1303:1321 the normal turnover of cell surface proteins 1303:1346 Consistent with other SIBLING-MMP pairs, the DSPP-MMP20 pair may play a role in the normal turnover of cell surface proteins and/or repair of pericellular matrix proteins of the basement membranes in the metabolically active duct epithelial system of the nephrons. 27666430 7 22 from role 1295:1298 arg1 repair 1355:1360 repair 1355:1360 repair 1355:1360 Consistent with other SIBLING-MMP pairs, the DSPP-MMP20 pair may play a role in the normal turnover of cell surface proteins and/or repair of pericellular matrix proteins of the basement membranes in the metabolically active duct epithelial system of the nephrons. 27666430 5 23 dep human 990:994 arg1 the 986:988 the 986:988 the 986:988 Our results show that MMP20 is expressed in all segments of the human and monkey nephron with marked intensity in the proximal and distal tubules, and was absent in the glomeruli. 27666430 5 23 dep human 990:994 arg1 nephron 1007:1013 nephron 1007:1013 nephron 1007:1013 Our results show that MMP20 is expressed in all segments of the human and monkey nephron with marked intensity in the proximal and distal tubules, and was absent in the glomeruli. 27666430 3 24 theme dentin 668:673 arg1 protein 682:688 dentin matrix protein 1 668:690 dentin matrix protein 1 668:690 Our earlier reports have shown the co-expression of three MMPs, MMP2, MMP3, and MMP9, with specific members of the SIBLING family: bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 27666430 2 25 theme glycoproteins 475:487 arg1 sialophosphoprotein 392:410 dentin sialophosphoprotein 385:410 dentin sialophosphoprotein (DSPP) 385:417 Furthermore, our report indicated that MMP20 co-expressed and potentially interacts with dentin sialophosphoprotein (DSPP), a member of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs). 27666430 2 25 theme glycoproteins 475:487 arg1 member 422:427 a member 420:427 a member of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) 420:498 Furthermore, our report indicated that MMP20 co-expressed and potentially interacts with dentin sialophosphoprotein (DSPP), a member of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs). 27666430 7 26 theme epithelial 1453:1462 arg1 system 1464:1469 the metabolically active duct epithelial system 1423:1469 the metabolically active duct epithelial system of the nephrons 1423:1485 Consistent with other SIBLING-MMP pairs, the DSPP-MMP20 pair may play a role in the normal turnover of cell surface proteins and/or repair of pericellular matrix proteins of the basement membranes in the metabolically active duct epithelial system of the nephrons. 27666430 7 27 theme normal 1307:1312 arg1 turnover 1314:1321 the normal turnover 1303:1321 the normal turnover of cell surface proteins 1303:1346 Consistent with other SIBLING-MMP pairs, the DSPP-MMP20 pair may play a role in the normal turnover of cell surface proteins and/or repair of pericellular matrix proteins of the basement membranes in the metabolically active duct epithelial system of the nephrons. 27666430 7 28 theme proteins 1385:1392 arg1 role 1295:1298 a role 1293:1298 a role in the normal turnover of cell surface proteins and/or repair of pericellular matrix proteins of the basement membranes 1293:1418 Consistent with other SIBLING-MMP pairs, the DSPP-MMP20 pair may play a role in the normal turnover of cell surface proteins and/or repair of pericellular matrix proteins of the basement membranes in the metabolically active duct epithelial system of the nephrons. 27666430 0 29 theme Metalloproteinase 7:23 arg1 Co-expression 28:40 Matrix Metalloproteinase 20 Co-expression 0:40 Matrix Metalloproteinase 20 Co-expression With Dentin Sialophosphoprotein in Human and Monkey Kidneys 0:100 Matrix Metalloproteinase 20 Co-expression With Dentin Sialophosphoprotein in Human and Monkey Kidneys. 27666430 3 30 theme matrix 675:680 arg1 protein 682:688 dentin matrix protein 1 668:690 dentin matrix protein 1 668:690 Our earlier reports have shown the co-expression of three MMPs, MMP2, MMP3, and MMP9, with specific members of the SIBLING family: bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 27666430 4 31 theme monkey 809:814 arg1 sections 823:830 human and monkey kidney sections 799:830 human and monkey kidney sections 799:830 This study investigated the expression of MMP20 and verified its co-expression with DSPP in human and monkey kidney sections and human mixed renal cells by IHC, in situ proximity ligation assay, and immunofluorescence. 27666430 3 32 with sialoprotein 637:648 arg1 members 601:607 specific members 592:607 specific members of the SIBLING family 592:629 Our earlier reports have shown the co-expression of three MMPs, MMP2, MMP3, and MMP9, with specific members of the SIBLING family: bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 27666430 2 33 theme dentin 385:390 arg1 sialophosphoprotein 392:410 dentin sialophosphoprotein 385:410 dentin sialophosphoprotein (DSPP) 385:417 Furthermore, our report indicated that MMP20 co-expressed and potentially interacts with dentin sialophosphoprotein (DSPP), a member of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs). 27666430 2 33 theme dentin 385:390 arg1 member 422:427 a member 420:427 a member of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) 420:498 Furthermore, our report indicated that MMP20 co-expressed and potentially interacts with dentin sialophosphoprotein (DSPP), a member of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs). 27666430 2 33 theme dentin 385:390 arg1 DSPP 413:416 DSPP 413:416 DSPP 413:416 Furthermore, our report indicated that MMP20 co-expressed and potentially interacts with dentin sialophosphoprotein (DSPP), a member of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs). 27666430 0 34 theme Matrix 0:5 arg1 Metalloproteinase 7:23 Matrix Metalloproteinase 20 0:26 Matrix Metalloproteinase 20 Co-expression With Dentin Sialophosphoprotein in Human and Monkey Kidneys 0:100 Matrix Metalloproteinase 20 Co-expression With Dentin Sialophosphoprotein in Human and Monkey Kidneys. 27666430 6 35 theme proximal 1155:1162 arg1 tubules 1188:1194 the proximal, distal, and collecting tubules 1151:1194 the proximal, distal, and collecting tubules 1151:1194 Furthermore, MMP20 co-expressed with DSPP in the proximal, distal, and collecting tubules, and in mixed renal cells. 27666430 5 36 from glomeruli 1095:1103 arg1 absent 1081:1086 absent 1081:1086 absent 1081:1086 Our results show that MMP20 is expressed in all segments of the human and monkey nephron with marked intensity in the proximal and distal tubules, and was absent in the glomeruli. 27666430 5 37 theme monkey 1000:1005 arg1 segments 974:981 all segments 970:981 all segments of the human and monkey nephron 970:1013 Our results show that MMP20 is expressed in all segments of the human and monkey nephron with marked intensity in the proximal and distal tubules, and was absent in the glomeruli. 27666430 1 38 theme human 273:277 arg1 glands 288:293 human salivary glands 273:293 human salivary glands 273:293 We recently reported the expression of matrix metalloproteinase 20 (MMP20), hitherto thought to be tooth specific, in the metabolically active ductal epithelial cells of human salivary glands. 27666430 2 39 link N-linked 466:473 arg1 SIBLINGs 490:497 SIBLINGs 490:497 SIBLINGs 490:497 Furthermore, our report indicated that MMP20 co-expressed and potentially interacts with dentin sialophosphoprotein (DSPP), a member of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs). 27666430 2 39 link N-linked 466:473 arg1 glycoproteins 475:487 the small integrin-binding ligand N-linked glycoproteins 432:487 the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) 432:498 Furthermore, our report indicated that MMP20 co-expressed and potentially interacts with dentin sialophosphoprotein (DSPP), a member of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs). 27666430 5 40 from intensity 1027:1035 arg1 tubules 1064:1070 the proximal and distal tubules 1040:1070 the proximal and distal tubules 1040:1070 Our results show that MMP20 is expressed in all segments of the human and monkey nephron with marked intensity in the proximal and distal tubules, and was absent in the glomeruli. 27666430 1 41 theme salivary 279:286 arg1 glands 288:293 human salivary glands 273:293 human salivary glands 273:293 We recently reported the expression of matrix metalloproteinase 20 (MMP20), hitherto thought to be tooth specific, in the metabolically active ductal epithelial cells of human salivary glands. 27666430 3 42 theme MMPs 559:562 arg1 co-expression 536:548 the co-expression 532:548 the co-expression of three MMPs, MMP2, MMP3, and MMP9, with specific members of the SIBLING family 532:629 Our earlier reports have shown the co-expression of three MMPs, MMP2, MMP3, and MMP9, with specific members of the SIBLING family: bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 27666430 3 42 theme MMPs 559:562 arg1 protein 682:688 dentin matrix protein 1 668:690 dentin matrix protein 1 668:690 Our earlier reports have shown the co-expression of three MMPs, MMP2, MMP3, and MMP9, with specific members of the SIBLING family: bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 27666430 3 42 theme MMPs 559:562 arg1 osteopontin 651:661 osteopontin 651:661 osteopontin 651:661 Our earlier reports have shown the co-expression of three MMPs, MMP2, MMP3, and MMP9, with specific members of the SIBLING family: bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 27666430 3 42 theme MMPs 559:562 arg1 sialoprotein 637:648 bone sialoprotein 632:648 bone sialoprotein 632:648 Our earlier reports have shown the co-expression of three MMPs, MMP2, MMP3, and MMP9, with specific members of the SIBLING family: bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 27666430 0 43 theme Dentin 47:52 arg1 Sialophosphoprotein 54:72 Dentin Sialophosphoprotein 47:72 Dentin Sialophosphoprotein 47:72 Matrix Metalloproteinase 20 Co-expression With Dentin Sialophosphoprotein in Human and Monkey Kidneys. 27666430 1 44 theme glands 288:293 arg1 cells 264:268 the metabolically active ductal epithelial cells 221:268 the metabolically active ductal epithelial cells of human salivary glands 221:293 We recently reported the expression of matrix metalloproteinase 20 (MMP20), hitherto thought to be tooth specific, in the metabolically active ductal epithelial cells of human salivary glands. 27666430 3 45 theme SIBLING 616:622 arg1 family 624:629 the SIBLING family 612:629 the SIBLING family 612:629 Our earlier reports have shown the co-expression of three MMPs, MMP2, MMP3, and MMP9, with specific members of the SIBLING family: bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 27666430 3 46 with co-expression 536:548 arg1 members 601:607 specific members 592:607 specific members of the SIBLING family 592:629 Our earlier reports have shown the co-expression of three MMPs, MMP2, MMP3, and MMP9, with specific members of the SIBLING family: bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 27666430 2 47 theme N-linked 466:473 arg1 SIBLINGs 490:497 SIBLINGs 490:497 SIBLINGs 490:497 Furthermore, our report indicated that MMP20 co-expressed and potentially interacts with dentin sialophosphoprotein (DSPP), a member of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs). 27666430 2 47 theme N-linked 466:473 arg1 glycoproteins 475:487 the small integrin-binding ligand N-linked glycoproteins 432:487 the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) 432:498 Furthermore, our report indicated that MMP20 co-expressed and potentially interacts with dentin sialophosphoprotein (DSPP), a member of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs). 27666430 4 48 theme in 868:869 arg1 assay 895:899 in situ proximity ligation assay 868:899 in situ proximity ligation assay 868:899 This study investigated the expression of MMP20 and verified its co-expression with DSPP in human and monkey kidney sections and human mixed renal cells by IHC, in situ proximity ligation assay, and immunofluorescence. 27666430 7 49 theme membranes 1410:1418 arg1 proteins 1385:1392 pericellular matrix proteins 1365:1392 pericellular matrix proteins of the basement membranes 1365:1418 Consistent with other SIBLING-MMP pairs, the DSPP-MMP20 pair may play a role in the normal turnover of cell surface proteins and/or repair of pericellular matrix proteins of the basement membranes in the metabolically active duct epithelial system of the nephrons. 27666430 2 50 gly glycoproteins 475:487 arg1 SIBLINGs 490:497 SIBLINGs 490:497 SIBLINGs 490:497 Furthermore, our report indicated that MMP20 co-expressed and potentially interacts with dentin sialophosphoprotein (DSPP), a member of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs). 27666430 2 50 gly glycoproteins 475:487 arg1 glycoproteins 475:487 the small integrin-binding ligand N-linked glycoproteins 432:487 the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) 432:498 Furthermore, our report indicated that MMP20 co-expressed and potentially interacts with dentin sialophosphoprotein (DSPP), a member of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs). 27666430 0 51 with Co-expression 28:40 arg1 Sialophosphoprotein 54:72 Dentin Sialophosphoprotein 47:72 Dentin Sialophosphoprotein 47:72 Matrix Metalloproteinase 20 Co-expression With Dentin Sialophosphoprotein in Human and Monkey Kidneys. 27666430 2 52 theme ligand 459:464 arg1 SIBLINGs 490:497 SIBLINGs 490:497 SIBLINGs 490:497 Furthermore, our report indicated that MMP20 co-expressed and potentially interacts with dentin sialophosphoprotein (DSPP), a member of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs). 27666430 2 52 theme ligand 459:464 arg1 glycoproteins 475:487 the small integrin-binding ligand N-linked glycoproteins 432:487 the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) 432:498 Furthermore, our report indicated that MMP20 co-expressed and potentially interacts with dentin sialophosphoprotein (DSPP), a member of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs). 27666430 4 53 theme renal 848:852 arg1 cells 854:858 human mixed renal cells 836:858 human mixed renal cells 836:858 This study investigated the expression of MMP20 and verified its co-expression with DSPP in human and monkey kidney sections and human mixed renal cells by IHC, in situ proximity ligation assay, and immunofluorescence. 27666430 7 54 theme cell 1326:1329 arg1 proteins 1339:1346 cell surface proteins 1326:1346 cell surface proteins 1326:1346 Consistent with other SIBLING-MMP pairs, the DSPP-MMP20 pair may play a role in the normal turnover of cell surface proteins and/or repair of pericellular matrix proteins of the basement membranes in the metabolically active duct epithelial system of the nephrons. 27666430 7 55 theme active 1441:1446 arg1 system 1464:1469 the metabolically active duct epithelial system 1423:1469 the metabolically active duct epithelial system of the nephrons 1423:1485 Consistent with other SIBLING-MMP pairs, the DSPP-MMP20 pair may play a role in the normal turnover of cell surface proteins and/or repair of pericellular matrix proteins of the basement membranes in the metabolically active duct epithelial system of the nephrons. 27666430 2 56 theme integrin-binding 442:457 arg1 SIBLINGs 490:497 SIBLINGs 490:497 SIBLINGs 490:497 Furthermore, our report indicated that MMP20 co-expressed and potentially interacts with dentin sialophosphoprotein (DSPP), a member of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs). 27666430 2 56 theme integrin-binding 442:457 arg1 glycoproteins 475:487 the small integrin-binding ligand N-linked glycoproteins 432:487 the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) 432:498 Furthermore, our report indicated that MMP20 co-expressed and potentially interacts with dentin sialophosphoprotein (DSPP), a member of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs). 27666430 4 57 theme mixed 842:846 arg1 cells 854:858 human mixed renal cells 836:858 human mixed renal cells 836:858 This study investigated the expression of MMP20 and verified its co-expression with DSPP in human and monkey kidney sections and human mixed renal cells by IHC, in situ proximity ligation assay, and immunofluorescence. 27666430 3 58 theme bone 632:635 arg1 sialoprotein 637:648 bone sialoprotein 632:648 bone sialoprotein 632:648 Our earlier reports have shown the co-expression of three MMPs, MMP2, MMP3, and MMP9, with specific members of the SIBLING family: bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 27666430 6 59 theme distal 1165:1170 arg1 tubules 1188:1194 the proximal, distal, and collecting tubules 1151:1194 the proximal, distal, and collecting tubules 1151:1194 Furthermore, MMP20 co-expressed with DSPP in the proximal, distal, and collecting tubules, and in mixed renal cells. 27666430 4 60 from co-expression 772:784 arg1 cells 854:858 human mixed renal cells 836:858 human mixed renal cells 836:858 This study investigated the expression of MMP20 and verified its co-expression with DSPP in human and monkey kidney sections and human mixed renal cells by IHC, in situ proximity ligation assay, and immunofluorescence. 27666430 4 60 from co-expression 772:784 arg1 sections 823:830 human and monkey kidney sections 799:830 human and monkey kidney sections 799:830 This study investigated the expression of MMP20 and verified its co-expression with DSPP in human and monkey kidney sections and human mixed renal cells by IHC, in situ proximity ligation assay, and immunofluorescence. 27666430 6 61 theme collecting 1177:1186 arg1 tubules 1188:1194 the proximal, distal, and collecting tubules 1151:1194 the proximal, distal, and collecting tubules 1151:1194 Furthermore, MMP20 co-expressed with DSPP in the proximal, distal, and collecting tubules, and in mixed renal cells. 27666430 1 62 from expression 128:137 arg1 cells 264:268 the metabolically active ductal epithelial cells 221:268 the metabolically active ductal epithelial cells of human salivary glands 221:293 We recently reported the expression of matrix metalloproteinase 20 (MMP20), hitherto thought to be tooth specific, in the metabolically active ductal epithelial cells of human salivary glands. 27666430 5 63 from absent 1081:1086 arg1 glomeruli 1095:1103 the glomeruli 1091:1103 the glomeruli 1091:1103 Our results show that MMP20 is expressed in all segments of the human and monkey nephron with marked intensity in the proximal and distal tubules, and was absent in the glomeruli. 27666430 7 64 theme basement 1401:1408 arg1 membranes 1410:1418 the basement membranes 1397:1418 the basement membranes 1397:1418 Consistent with other SIBLING-MMP pairs, the DSPP-MMP20 pair may play a role in the normal turnover of cell surface proteins and/or repair of pericellular matrix proteins of the basement membranes in the metabolically active duct epithelial system of the nephrons. 27666430 4 65 theme MMP20 749:753 arg1 expression 735:744 the expression 731:744 the expression of MMP20 731:753 This study investigated the expression of MMP20 and verified its co-expression with DSPP in human and monkey kidney sections and human mixed renal cells by IHC, in situ proximity ligation assay, and immunofluorescence. 27666430 7 66 theme nephrons 1478:1485 arg1 system 1464:1469 the metabolically active duct epithelial system 1423:1469 the metabolically active duct epithelial system of the nephrons 1423:1485 Consistent with other SIBLING-MMP pairs, the DSPP-MMP20 pair may play a role in the normal turnover of cell surface proteins and/or repair of pericellular matrix proteins of the basement membranes in the metabolically active duct epithelial system of the nephrons. 27666430 3 67 theme family 624:629 arg1 members 601:607 specific members 592:607 specific members of the SIBLING family 592:629 Our earlier reports have shown the co-expression of three MMPs, MMP2, MMP3, and MMP9, with specific members of the SIBLING family: bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 27666430 3 68 theme specific 592:599 arg1 members 601:607 specific members 592:607 specific members of the SIBLING family 592:629 Our earlier reports have shown the co-expression of three MMPs, MMP2, MMP3, and MMP9, with specific members of the SIBLING family: bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 27666430 1 69 theme matrix 142:147 arg1 metalloproteinase 149:165 matrix metalloproteinase 20 142:168 matrix metalloproteinase 20 (MMP20) 142:176 We recently reported the expression of matrix metalloproteinase 20 (MMP20), hitherto thought to be tooth specific, in the metabolically active ductal epithelial cells of human salivary glands. 27666430 1 69 theme matrix 142:147 arg1 MMP20 171:175 MMP20 171:175 MMP20 171:175 We recently reported the expression of matrix metalloproteinase 20 (MMP20), hitherto thought to be tooth specific, in the metabolically active ductal epithelial cells of human salivary glands. 27666430 3 70 with protein 682:688 arg1 members 601:607 specific members 592:607 specific members of the SIBLING family 592:629 Our earlier reports have shown the co-expression of three MMPs, MMP2, MMP3, and MMP9, with specific members of the SIBLING family: bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. 27666430 5 71 theme human 990:994 arg1 segments 974:981 all segments 970:981 all segments of the human and monkey nephron 970:1013 Our results show that MMP20 is expressed in all segments of the human and monkey nephron with marked intensity in the proximal and distal tubules, and was absent in the glomeruli. 27666430 7 72 theme other 1239:1243 arg1 pairs 1257:1261 other SIBLING-MMP pairs 1239:1261 other SIBLING-MMP pairs 1239:1261 Consistent with other SIBLING-MMP pairs, the DSPP-MMP20 pair may play a role in the normal turnover of cell surface proteins and/or repair of pericellular matrix proteins of the basement membranes in the metabolically active duct epithelial system of the nephrons. 27666430 1 73 theme metalloproteinase 149:165 arg1 expression 128:137 the expression 124:137 the expression of matrix metalloproteinase 20 (MMP20), hitherto thought to be tooth specific, in the metabolically active ductal epithelial cells of human salivary glands 124:293 We recently reported the expression of matrix metalloproteinase 20 (MMP20), hitherto thought to be tooth specific, in the metabolically active ductal epithelial cells of human salivary glands. 27666430 4 74 with co-expression 772:784 arg1 DSPP 791:794 DSPP 791:794 DSPP 791:794 This study investigated the expression of MMP20 and verified its co-expression with DSPP in human and monkey kidney sections and human mixed renal cells by IHC, in situ proximity ligation assay, and immunofluorescence. 27666430 0 75 theme Human 77:81 arg1 Kidneys 94:100 Human and Monkey Kidneys 77:100 Human and Monkey Kidneys 77:100 Matrix Metalloproteinase 20 Co-expression With Dentin Sialophosphoprotein in Human and Monkey Kidneys. 27666430 0 76 from Co-expression 28:40 arg1 Kidneys 94:100 Human and Monkey Kidneys 77:100 Human and Monkey Kidneys 77:100 Matrix Metalloproteinase 20 Co-expression With Dentin Sialophosphoprotein in Human and Monkey Kidneys. 27666430 7 77 theme SIBLING-MMP 1245:1255 arg1 pairs 1257:1261 other SIBLING-MMP pairs 1239:1261 other SIBLING-MMP pairs 1239:1261 Consistent with other SIBLING-MMP pairs, the DSPP-MMP20 pair may play a role in the normal turnover of cell surface proteins and/or repair of pericellular matrix proteins of the basement membranes in the metabolically active duct epithelial system of the nephrons. 27666430 2 78 theme small 436:440 arg1 SIBLINGs 490:497 SIBLINGs 490:497 SIBLINGs 490:497 Furthermore, our report indicated that MMP20 co-expressed and potentially interacts with dentin sialophosphoprotein (DSPP), a member of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs). 27666430 2 78 theme small 436:440 arg1 glycoproteins 475:487 the small integrin-binding ligand N-linked glycoproteins 432:487 the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) 432:498 Furthermore, our report indicated that MMP20 co-expressed and potentially interacts with dentin sialophosphoprotein (DSPP), a member of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs). 27666430 7 79 theme DSPP-MMP20 1268:1277 arg1 pair 1279:1282 the DSPP-MMP20 pair 1264:1282 the DSPP-MMP20 pair 1264:1282 Consistent with other SIBLING-MMP pairs, the DSPP-MMP20 pair may play a role in the normal turnover of cell surface proteins and/or repair of pericellular matrix proteins of the basement membranes in the metabolically active duct epithelial system of the nephrons. 27666430 4 80 dep in 868:869 arg1 situ 871:874 situ 871:874 situ 871:874 This study investigated the expression of MMP20 and verified its co-expression with DSPP in human and monkey kidney sections and human mixed renal cells by IHC, in situ proximity ligation assay, and immunofluorescence. 26853939 5 0 from transitions 754:764 arg1 IR 769:770 IR 769:770 IR upon ligand binding 769:790 The resulting model provides a foundation for investigation of structural transitions in IR upon ligand binding. 26853939 5 1 from investigation 726:738 arg1 IR 769:770 IR 769:770 IR upon ligand binding 769:790 The resulting model provides a foundation for investigation of structural transitions in IR upon ligand binding. 26853939 0 2 theme Insert 99:104 arg1 Domain 106:111 the Insert Domain 95:111 the Insert Domain 95:111 Higher-Resolution Structure of the Human Insulin Receptor Ectodomain: Multi-Modal Inclusion of the Insert Domain. 26853939 3 3 theme first 491:495 arg1 domains 528:534 the first and third fibronectin type III domains 487:534 the first and third fibronectin type III domains 487:534 Here, we revise this structure using new diffraction data to 3.3 Å resolution that allow improved modeling of the N-linked glycans, the first and third fibronectin type III domains, and the insert domain. 26853939 3 4 theme fibronectin 507:517 arg1 domains 528:534 the first and third fibronectin type III domains 487:534 the first and third fibronectin type III domains 487:534 Here, we revise this structure using new diffraction data to 3.3 Å resolution that allow improved modeling of the N-linked glycans, the first and third fibronectin type III domains, and the insert domain. 26853939 5 5 theme resulting 684:692 arg1 model 694:698 The resulting model 680:698 The resulting model 680:698 The resulting model provides a foundation for investigation of structural transitions in IR upon ligand binding. 26853939 3 6 theme improved 444:451 arg1 modeling 453:460 improved modeling 444:460 improved modeling of the N-linked glycans, the first and third fibronectin type III domains, and the insert domain 444:557 Here, we revise this structure using new diffraction data to 3.3 Å resolution that allow improved modeling of the N-linked glycans, the first and third fibronectin type III domains, and the insert domain. 26853939 3 7 theme diffraction 396:406 arg1 data 408:411 new diffraction data 392:411 new diffraction data to 3.3 Å resolution that allow improved modeling of the N-linked glycans, the first and third fibronectin type III domains, and the insert domain 392:557 Here, we revise this structure using new diffraction data to 3.3 Å resolution that allow improved modeling of the N-linked glycans, the first and third fibronectin type III domains, and the insert domain. 26853939 0 8 theme Domain 106:111 arg1 Inclusion 82:90 Multi-Modal Inclusion 70:90 Higher-Resolution Structure of the Human Insulin Receptor Ectodomain: Multi-Modal Inclusion of the Insert Domain. 0:112 Higher-Resolution Structure of the Human Insulin Receptor Ectodomain: Multi-Modal Inclusion of the Insert Domain. 26853939 4 9 theme dynamics 597:604 arg1 strategy 606:613 A novel haptic interactive molecular dynamics strategy 560:613 A novel haptic interactive molecular dynamics strategy 560:613 A novel haptic interactive molecular dynamics strategy was used to aid fitting to low-resolution electron density maps. 26853939 5 10 from IR 769:770 arg1 investigation 726:738 investigation 726:738 investigation of structural transitions in IR upon ligand binding 726:790 The resulting model provides a foundation for investigation of structural transitions in IR upon ligand binding. 26853939 3 11 theme type 519:522 arg1 domains 528:534 the first and third fibronectin type III domains 487:534 the first and third fibronectin type III domains 487:534 Here, we revise this structure using new diffraction data to 3.3 Å resolution that allow improved modeling of the N-linked glycans, the first and third fibronectin type III domains, and the insert domain. 26853939 1 12 theme nutrient 173:180 arg1 uptake 182:187 nutrient uptake 173:187 nutrient uptake 173:187 Insulin receptor (IR) signaling is critical to controlling nutrient uptake and metabolism. 26853939 0 13 theme Higher-Resolution 0:16 arg1 Structure 18:26 Higher-Resolution Structure 0:26 Higher-Resolution Structure of the Human Insulin Receptor Ectodomain: Multi-Modal Inclusion of the Insert Domain. 0:112 Higher-Resolution Structure of the Human Insulin Receptor Ectodomain: Multi-Modal Inclusion of the Insert Domain. 26853939 3 14 theme new 392:394 arg1 data 408:411 new diffraction data 392:411 new diffraction data to 3.3 Å resolution that allow improved modeling of the N-linked glycans, the first and third fibronectin type III domains, and the insert domain 392:557 Here, we revise this structure using new diffraction data to 3.3 Å resolution that allow improved modeling of the N-linked glycans, the first and third fibronectin type III domains, and the insert domain. 26853939 0 15 dep Structure 18:26 arg1 Inclusion 82:90 Multi-Modal Inclusion 70:90 Higher-Resolution Structure of the Human Insulin Receptor Ectodomain: Multi-Modal Inclusion of the Insert Domain. 0:112 Higher-Resolution Structure of the Human Insulin Receptor Ectodomain: Multi-Modal Inclusion of the Insert Domain. 26853939 2 16 theme IR 279:280 arg1 ectodomain 282:291 the IR ectodomain 275:291 the IR ectodomain 275:291 However, only a low-resolution (3.8 Å) structure currently exists for the IR ectodomain, with some segments ill-defined or unmodeled due to disorder. 26853939 3 17 theme Å 420:420 arg1 resolution 422:431 3.3 Å resolution 416:431 3.3 Å resolution 416:431 Here, we revise this structure using new diffraction data to 3.3 Å resolution that allow improved modeling of the N-linked glycans, the first and third fibronectin type III domains, and the insert domain. 26853939 5 18 theme ligand 777:782 arg1 binding 784:790 ligand binding 777:790 ligand binding 777:790 The resulting model provides a foundation for investigation of structural transitions in IR upon ligand binding. 26853939 2 19 dep segments 304:311 arg1 unmodeled 328:336 unmodeled 328:336 unmodeled due to disorder 328:352 However, only a low-resolution (3.8 Å) structure currently exists for the IR ectodomain, with some segments ill-defined or unmodeled due to disorder. 26853939 2 19 dep segments 304:311 arg1 ill-defined 313:323 ill-defined 313:323 ill-defined 313:323 However, only a low-resolution (3.8 Å) structure currently exists for the IR ectodomain, with some segments ill-defined or unmodeled due to disorder. 26853939 4 20 theme novel 562:566 arg1 strategy 606:613 A novel haptic interactive molecular dynamics strategy 560:613 A novel haptic interactive molecular dynamics strategy 560:613 A novel haptic interactive molecular dynamics strategy was used to aid fitting to low-resolution electron density maps. 26853939 0 21 theme Insulin 41:47 arg1 Ectodomain 58:67 the Human Insulin Receptor Ectodomain 31:67 the Human Insulin Receptor Ectodomain 31:67 Higher-Resolution Structure of the Human Insulin Receptor Ectodomain: Multi-Modal Inclusion of the Insert Domain. 26853939 4 22 theme low-resolution 642:655 arg1 maps 674:677 low-resolution electron density maps 642:677 low-resolution electron density maps 642:677 A novel haptic interactive molecular dynamics strategy was used to aid fitting to low-resolution electron density maps. 26853939 3 23 link N-linked 469:476 arg1 glycans 478:484 the N-linked glycans 465:484 the N-linked glycans 465:484 Here, we revise this structure using new diffraction data to 3.3 Å resolution that allow improved modeling of the N-linked glycans, the first and third fibronectin type III domains, and the insert domain. 26853939 2 24 theme low-resolution 221:234 arg1 structure 244:252 only a low-resolution (3.8 Å) structure 214:252 only a low-resolution (3.8 Å) structure 214:252 However, only a low-resolution (3.8 Å) structure currently exists for the IR ectodomain, with some segments ill-defined or unmodeled due to disorder. 26853939 2 24 theme low-resolution 221:234 arg1 Å 241:241 3.8 Å 237:241 3.8 Å 237:241 However, only a low-resolution (3.8 Å) structure currently exists for the IR ectodomain, with some segments ill-defined or unmodeled due to disorder. 26853939 4 25 theme molecular 587:595 arg1 strategy 606:613 A novel haptic interactive molecular dynamics strategy 560:613 A novel haptic interactive molecular dynamics strategy 560:613 A novel haptic interactive molecular dynamics strategy was used to aid fitting to low-resolution electron density maps. 26853939 0 26 theme Human 35:39 arg1 Ectodomain 58:67 the Human Insulin Receptor Ectodomain 31:67 the Human Insulin Receptor Ectodomain 31:67 Higher-Resolution Structure of the Human Insulin Receptor Ectodomain: Multi-Modal Inclusion of the Insert Domain. 26853939 4 27 theme interactive 575:585 arg1 strategy 606:613 A novel haptic interactive molecular dynamics strategy 560:613 A novel haptic interactive molecular dynamics strategy 560:613 A novel haptic interactive molecular dynamics strategy was used to aid fitting to low-resolution electron density maps. 26853939 0 28 theme Ectodomain 58:67 arg1 Structure 18:26 Higher-Resolution Structure 0:26 Higher-Resolution Structure of the Human Insulin Receptor Ectodomain: Multi-Modal Inclusion of the Insert Domain. 0:112 Higher-Resolution Structure of the Human Insulin Receptor Ectodomain: Multi-Modal Inclusion of the Insert Domain. 26853939 5 29 theme transitions 754:764 arg1 investigation 726:738 investigation 726:738 investigation of structural transitions in IR upon ligand binding 726:790 The resulting model provides a foundation for investigation of structural transitions in IR upon ligand binding. 26853939 3 30 theme domains 528:534 arg1 modeling 453:460 improved modeling 444:460 improved modeling of the N-linked glycans, the first and third fibronectin type III domains, and the insert domain 444:557 Here, we revise this structure using new diffraction data to 3.3 Å resolution that allow improved modeling of the N-linked glycans, the first and third fibronectin type III domains, and the insert domain. 26853939 4 31 used used 619:622 arg2 strategy 606:613 A novel haptic interactive molecular dynamics strategy 560:613 A novel haptic interactive molecular dynamics strategy 560:613 A novel haptic interactive molecular dynamics strategy was used to aid fitting to low-resolution electron density maps. 26853939 1 32 theme Insulin 114:120 arg1 IR 132:133 IR 132:133 IR 132:133 Insulin receptor (IR) signaling is critical to controlling nutrient uptake and metabolism. 26853939 1 32 theme Insulin 114:120 arg1 receptor 122:129 Insulin receptor 114:129 Insulin receptor (IR) signaling 114:144 Insulin receptor (IR) signaling is critical to controlling nutrient uptake and metabolism. 26853939 0 33 theme Receptor 49:56 arg1 Ectodomain 58:67 the Human Insulin Receptor Ectodomain 31:67 the Human Insulin Receptor Ectodomain 31:67 Higher-Resolution Structure of the Human Insulin Receptor Ectodomain: Multi-Modal Inclusion of the Insert Domain. 26853939 1 34 theme receptor 122:129 arg1 signaling 136:144 Insulin receptor (IR) signaling 114:144 Insulin receptor (IR) signaling 114:144 Insulin receptor (IR) signaling is critical to controlling nutrient uptake and metabolism. 26853939 4 35 theme electron 657:664 arg1 maps 674:677 low-resolution electron density maps 642:677 low-resolution electron density maps 642:677 A novel haptic interactive molecular dynamics strategy was used to aid fitting to low-resolution electron density maps. 26853939 3 36 theme third 501:505 arg1 domains 528:534 the first and third fibronectin type III domains 487:534 the first and third fibronectin type III domains 487:534 Here, we revise this structure using new diffraction data to 3.3 Å resolution that allow improved modeling of the N-linked glycans, the first and third fibronectin type III domains, and the insert domain. 26853939 4 37 theme density 666:672 arg1 maps 674:677 low-resolution electron density maps 642:677 low-resolution electron density maps 642:677 A novel haptic interactive molecular dynamics strategy was used to aid fitting to low-resolution electron density maps. 26853939 0 38 theme Multi-Modal 70:80 arg1 Inclusion 82:90 Multi-Modal Inclusion 70:90 Higher-Resolution Structure of the Human Insulin Receptor Ectodomain: Multi-Modal Inclusion of the Insert Domain. 0:112 Higher-Resolution Structure of the Human Insulin Receptor Ectodomain: Multi-Modal Inclusion of the Insert Domain. 26853939 3 39 theme insert 545:550 arg1 domain 552:557 the insert domain 541:557 the insert domain 541:557 Here, we revise this structure using new diffraction data to 3.3 Å resolution that allow improved modeling of the N-linked glycans, the first and third fibronectin type III domains, and the insert domain. 26853939 4 40 theme haptic 568:573 arg1 strategy 606:613 A novel haptic interactive molecular dynamics strategy 560:613 A novel haptic interactive molecular dynamics strategy 560:613 A novel haptic interactive molecular dynamics strategy was used to aid fitting to low-resolution electron density maps. 26853939 3 41 theme N-linked 469:476 arg1 glycans 478:484 the N-linked glycans 465:484 the N-linked glycans 465:484 Here, we revise this structure using new diffraction data to 3.3 Å resolution that allow improved modeling of the N-linked glycans, the first and third fibronectin type III domains, and the insert domain. 26853939 5 42 theme structural 743:752 arg1 transitions 754:764 structural transitions 743:764 structural transitions in IR upon ligand binding 743:790 The resulting model provides a foundation for investigation of structural transitions in IR upon ligand binding. 26853939 3 43 theme domain 552:557 arg1 modeling 453:460 improved modeling 444:460 improved modeling of the N-linked glycans, the first and third fibronectin type III domains, and the insert domain 444:557 Here, we revise this structure using new diffraction data to 3.3 Å resolution that allow improved modeling of the N-linked glycans, the first and third fibronectin type III domains, and the insert domain. 26853939 3 44 theme glycans 478:484 arg1 modeling 453:460 improved modeling 444:460 improved modeling of the N-linked glycans, the first and third fibronectin type III domains, and the insert domain 444:557 Here, we revise this structure using new diffraction data to 3.3 Å resolution that allow improved modeling of the N-linked glycans, the first and third fibronectin type III domains, and the insert domain. 26537759 4 0 theme intriguing 556:565 arg1 option 567:572 an intriguing option 553:572 an intriguing option to rationally guide glycoengineering 553:609 Computational modeling offers an intriguing option to rationally guide glycoengineering, but the high parametric demands of current modeling approaches pose challenges to their application. 26537759 7 1 theme glycosyltransferase 1086:1104 arg1 knock-out 1106:1114 the endogenous secretome following glycosyltransferase knock-out 1051:1114 the endogenous secretome following glycosyltransferase knock-out in different Chinese hamster ovary (CHO) cell lines 1051:1166 We use this method to predict and experimentally validate glycoprofiles on EPO, IgG as well as the endogenous secretome following glycosyltransferase knock-out in different Chinese hamster ovary (CHO) cell lines. 26537759 1 2 theme most 170:173 arg1 biotherapeutics 187:201 most recombinant biotherapeutics 170:201 most recombinant biotherapeutics 170:201 Glycosylation is a critical quality attribute of most recombinant biotherapeutics. 26537759 4 3 theme current 647:653 arg1 approaches 664:673 current modeling approaches 647:673 current modeling approaches 647:673 Computational modeling offers an intriguing option to rationally guide glycoengineering, but the high parametric demands of current modeling approaches pose challenges to their application. 26537759 7 4 theme endogenous 1055:1064 arg1 knock-out 1106:1114 the endogenous secretome following glycosyltransferase knock-out 1051:1114 the endogenous secretome following glycosyltransferase knock-out in different Chinese hamster ovary (CHO) cell lines 1051:1166 We use this method to predict and experimentally validate glycoprofiles on EPO, IgG as well as the endogenous secretome following glycosyltransferase knock-out in different Chinese hamster ovary (CHO) cell lines. 26537759 1 5 theme recombinant 175:185 arg1 biotherapeutics 187:201 most recombinant biotherapeutics 170:201 most recombinant biotherapeutics 170:201 Glycosylation is a critical quality attribute of most recombinant biotherapeutics. 26537759 5 6 theme chain 816:820 arg1 modeling 822:829 Markov chain modeling 809:829 Markov chain modeling 809:829 Here we present a novel low-parameter approach to describe glycosylation using flux-balance and Markov chain modeling. 26537759 8 7 from efforts 1292:1298 arg1 factories 1318:1326 mammalian cell factories 1303:1326 mammalian cell factories for biopharmaceutical production 1303:1359 Our approach offers a flexible and user-friendly platform that can serve as a basis for powerful computational engineering efforts in mammalian cell factories for biopharmaceutical production. 26537759 5 8 theme novel 731:735 arg1 approach 751:758 a novel low-parameter approach 729:758 a novel low-parameter approach to describe glycosylation using flux-balance and Markov chain modeling 729:829 Here we present a novel low-parameter approach to describe glycosylation using flux-balance and Markov chain modeling. 26537759 7 9 theme secretome 1066:1074 arg1 knock-out 1106:1114 the endogenous secretome following glycosyltransferase knock-out 1051:1114 the endogenous secretome following glycosyltransferase knock-out in different Chinese hamster ovary (CHO) cell lines 1051:1166 We use this method to predict and experimentally validate glycoprofiles on EPO, IgG as well as the endogenous secretome following glycosyltransferase knock-out in different Chinese hamster ovary (CHO) cell lines. 26537759 4 10 theme approaches 664:673 arg1 demands 636:642 the high parametric demands 616:642 the high parametric demands of current modeling approaches 616:673 Computational modeling offers an intriguing option to rationally guide glycoengineering, but the high parametric demands of current modeling approaches pose challenges to their application. 26537759 0 11 theme model-driven 90:101 arg1 glycoengineering 103:118 model-driven glycoengineering 90:118 model-driven glycoengineering 90:118 A Markov chain model for N-linked protein glycosylation--towards a low-parameter tool for model-driven glycoengineering. 26537759 5 12 theme low-parameter 737:749 arg1 approach 751:758 a novel low-parameter approach 729:758 a novel low-parameter approach to describe glycosylation using flux-balance and Markov chain modeling 729:829 Here we present a novel low-parameter approach to describe glycosylation using flux-balance and Markov chain modeling. 26537759 4 13 theme modeling 655:662 arg1 approaches 664:673 current modeling approaches 647:673 current modeling approaches 647:673 Computational modeling offers an intriguing option to rationally guide glycoengineering, but the high parametric demands of current modeling approaches pose challenges to their application. 26537759 3 14 theme reaction 399:406 arg1 networks 408:415 the complex reaction networks 387:415 the complex reaction networks underlying glycosylation and the vast number of different glycans that can be synthesized in a host cell 387:520 However, glycoengineering can be extraordinarily difficult given the complex reaction networks underlying glycosylation and the vast number of different glycans that can be synthesized in a host cell. 26537759 4 15 theme Computational 523:535 arg1 modeling 537:544 Computational modeling 523:544 Computational modeling 523:544 Computational modeling offers an intriguing option to rationally guide glycoengineering, but the high parametric demands of current modeling approaches pose challenges to their application. 26537759 1 16 theme biotherapeutics 187:201 arg1 attribute 157:165 a critical quality attribute 138:165 a critical quality attribute of most recombinant biotherapeutics 138:201 Glycosylation is a critical quality attribute of most recombinant biotherapeutics. 26537759 1 16 theme biotherapeutics 187:201 arg1 Glycosylation 121:133 Glycosylation 121:133 Glycosylation 121:133 Glycosylation is a critical quality attribute of most recombinant biotherapeutics. 26537759 8 17 theme biopharmaceutical 1332:1348 arg1 production 1350:1359 biopharmaceutical production 1332:1359 biopharmaceutical production 1332:1359 Our approach offers a flexible and user-friendly platform that can serve as a basis for powerful computational engineering efforts in mammalian cell factories for biopharmaceutical production. 26537759 0 18 theme N-linked 25:32 arg1 protein 34:40 N-linked protein 25:40 N-linked protein 25:40 A Markov chain model for N-linked protein glycosylation--towards a low-parameter tool for model-driven glycoengineering. 26537759 8 19 theme engineering 1280:1290 arg1 efforts 1292:1298 powerful computational engineering efforts 1257:1298 powerful computational engineering efforts in mammalian cell factories for biopharmaceutical production 1257:1359 Our approach offers a flexible and user-friendly platform that can serve as a basis for powerful computational engineering efforts in mammalian cell factories for biopharmaceutical production. 26537759 0 20 theme Markov 2:7 arg1 model 15:19 A Markov chain model 0:19 A Markov chain model for N-linked protein 0:40 A Markov chain model for N-linked protein glycosylation--towards a low-parameter tool for model-driven glycoengineering. 26537759 6 21 theme glycosylation 885:897 arg1 complexity 871:880 the biological complexity 856:880 the biological complexity of glycosylation 856:897 The model recapitulates the biological complexity of glycosylation, but does not require user-provided kinetic information. 26537759 8 22 theme user-friendly 1204:1216 arg1 platform 1218:1225 a flexible and user-friendly platform 1189:1225 a flexible and user-friendly platform that can serve as a basis for powerful computational engineering efforts in mammalian cell factories for biopharmaceutical production 1189:1359 Our approach offers a flexible and user-friendly platform that can serve as a basis for powerful computational engineering efforts in mammalian cell factories for biopharmaceutical production. 26537759 8 22 theme user-friendly 1204:1216 arg1 basis 1247:1251 a basis 1245:1251 a basis for powerful computational engineering efforts in mammalian cell factories for biopharmaceutical production 1245:1359 Our approach offers a flexible and user-friendly platform that can serve as a basis for powerful computational engineering efforts in mammalian cell factories for biopharmaceutical production. 26537759 7 23 from knock-out 1106:1114 arg1 lines 1162:1166 different Chinese hamster ovary (CHO) cell lines 1119:1166 different Chinese hamster ovary (CHO) cell lines 1119:1166 We use this method to predict and experimentally validate glycoprofiles on EPO, IgG as well as the endogenous secretome following glycosyltransferase knock-out in different Chinese hamster ovary (CHO) cell lines. 26537759 4 24 theme high 620:623 arg1 demands 636:642 the high parametric demands 616:642 the high parametric demands of current modeling approaches 616:673 Computational modeling offers an intriguing option to rationally guide glycoengineering, but the high parametric demands of current modeling approaches pose challenges to their application. 26537759 6 25 theme user-provided 921:933 arg1 information 943:953 user-provided kinetic information 921:953 user-provided kinetic information 921:953 The model recapitulates the biological complexity of glycosylation, but does not require user-provided kinetic information. 26537759 0 26 link N-linked 25:32 arg1 protein 34:40 N-linked protein 25:40 N-linked protein 25:40 A Markov chain model for N-linked protein glycosylation--towards a low-parameter tool for model-driven glycoengineering. 26537759 7 27 from glycoprofiles 1014:1026 arg1 knock-out 1106:1114 the endogenous secretome following glycosyltransferase knock-out 1051:1114 the endogenous secretome following glycosyltransferase knock-out in different Chinese hamster ovary (CHO) cell lines 1051:1166 We use this method to predict and experimentally validate glycoprofiles on EPO, IgG as well as the endogenous secretome following glycosyltransferase knock-out in different Chinese hamster ovary (CHO) cell lines. 26537759 7 27 from glycoprofiles 1014:1026 arg1 IgG 1036:1038 IgG 1036:1038 IgG 1036:1038 We use this method to predict and experimentally validate glycoprofiles on EPO, IgG as well as the endogenous secretome following glycosyltransferase knock-out in different Chinese hamster ovary (CHO) cell lines. 26537759 7 27 from glycoprofiles 1014:1026 arg1 EPO 1031:1033 EPO 1031:1033 EPO 1031:1033 We use this method to predict and experimentally validate glycoprofiles on EPO, IgG as well as the endogenous secretome following glycosyltransferase knock-out in different Chinese hamster ovary (CHO) cell lines. 26537759 8 28 theme cell 1313:1316 arg1 factories 1318:1326 mammalian cell factories 1303:1326 mammalian cell factories for biopharmaceutical production 1303:1359 Our approach offers a flexible and user-friendly platform that can serve as a basis for powerful computational engineering efforts in mammalian cell factories for biopharmaceutical production. 26537759 8 29 theme computational 1266:1278 arg1 efforts 1292:1298 powerful computational engineering efforts 1257:1298 powerful computational engineering efforts in mammalian cell factories for biopharmaceutical production 1257:1359 Our approach offers a flexible and user-friendly platform that can serve as a basis for powerful computational engineering efforts in mammalian cell factories for biopharmaceutical production. 26537759 3 30 gly glycosylation 428:440 arg1 glycans 475:481 different glycans 465:481 different glycans that can be synthesized in a host cell 465:520 However, glycoengineering can be extraordinarily difficult given the complex reaction networks underlying glycosylation and the vast number of different glycans that can be synthesized in a host cell. 26537759 0 31 theme chain 9:13 arg1 model 15:19 A Markov chain model 0:19 A Markov chain model for N-linked protein 0:40 A Markov chain model for N-linked protein glycosylation--towards a low-parameter tool for model-driven glycoengineering. 26537759 7 32 from EPO 1031:1033 arg1 lines 1162:1166 different Chinese hamster ovary (CHO) cell lines 1119:1166 different Chinese hamster ovary (CHO) cell lines 1119:1166 We use this method to predict and experimentally validate glycoprofiles on EPO, IgG as well as the endogenous secretome following glycosyltransferase knock-out in different Chinese hamster ovary (CHO) cell lines. 26537759 3 33 theme glycans 475:481 arg1 number 455:460 the vast number 446:460 the vast number of different glycans that can be synthesized in a host cell 446:520 However, glycoengineering can be extraordinarily difficult given the complex reaction networks underlying glycosylation and the vast number of different glycans that can be synthesized in a host cell. 26537759 3 33 theme glycans 475:481 arg1 glycosylation 428:440 glycosylation 428:440 glycosylation 428:440 However, glycoengineering can be extraordinarily difficult given the complex reaction networks underlying glycosylation and the vast number of different glycans that can be synthesized in a host cell. 26537759 4 34 theme parametric 625:634 arg1 demands 636:642 the high parametric demands 616:642 the high parametric demands of current modeling approaches 616:673 Computational modeling offers an intriguing option to rationally guide glycoengineering, but the high parametric demands of current modeling approaches pose challenges to their application. 26537759 5 35 theme Markov 809:814 arg1 modeling 822:829 Markov chain modeling 809:829 Markov chain modeling 809:829 Here we present a novel low-parameter approach to describe glycosylation using flux-balance and Markov chain modeling. 26537759 2 36 theme glycoforms 263:272 arg1 control 252:258 careful control 244:258 careful control of glycoforms 244:272 Consequently, drug development requires careful control of glycoforms to meet bioactivity and biosafety requirements. 26537759 6 37 theme biological 860:869 arg1 complexity 871:880 the biological complexity 856:880 the biological complexity of glycosylation 856:897 The model recapitulates the biological complexity of glycosylation, but does not require user-provided kinetic information. 26537759 3 38 theme host 512:515 arg1 cell 517:520 a host cell 510:520 a host cell 510:520 However, glycoengineering can be extraordinarily difficult given the complex reaction networks underlying glycosylation and the vast number of different glycans that can be synthesized in a host cell. 26537759 8 39 theme powerful 1257:1264 arg1 efforts 1292:1298 powerful computational engineering efforts 1257:1298 powerful computational engineering efforts in mammalian cell factories for biopharmaceutical production 1257:1359 Our approach offers a flexible and user-friendly platform that can serve as a basis for powerful computational engineering efforts in mammalian cell factories for biopharmaceutical production. 26537759 7 40 theme ovary 1145:1149 arg1 lines 1162:1166 different Chinese hamster ovary (CHO) cell lines 1119:1166 different Chinese hamster ovary (CHO) cell lines 1119:1166 We use this method to predict and experimentally validate glycoprofiles on EPO, IgG as well as the endogenous secretome following glycosyltransferase knock-out in different Chinese hamster ovary (CHO) cell lines. 26537759 3 41 theme different 465:473 arg1 glycans 475:481 different glycans 465:481 different glycans that can be synthesized in a host cell 465:520 However, glycoengineering can be extraordinarily difficult given the complex reaction networks underlying glycosylation and the vast number of different glycans that can be synthesized in a host cell. 26537759 7 42 theme cell 1157:1160 arg1 lines 1162:1166 different Chinese hamster ovary (CHO) cell lines 1119:1166 different Chinese hamster ovary (CHO) cell lines 1119:1166 We use this method to predict and experimentally validate glycoprofiles on EPO, IgG as well as the endogenous secretome following glycosyltransferase knock-out in different Chinese hamster ovary (CHO) cell lines. 26537759 2 43 theme careful 244:250 arg1 control 252:258 careful control 244:258 careful control of glycoforms 244:272 Consequently, drug development requires careful control of glycoforms to meet bioactivity and biosafety requirements. 26537759 7 44 theme different 1119:1127 arg1 lines 1162:1166 different Chinese hamster ovary (CHO) cell lines 1119:1166 different Chinese hamster ovary (CHO) cell lines 1119:1166 We use this method to predict and experimentally validate glycoprofiles on EPO, IgG as well as the endogenous secretome following glycosyltransferase knock-out in different Chinese hamster ovary (CHO) cell lines. 26537759 7 45 from IgG 1036:1038 arg1 lines 1162:1166 different Chinese hamster ovary (CHO) cell lines 1119:1166 different Chinese hamster ovary (CHO) cell lines 1119:1166 We use this method to predict and experimentally validate glycoprofiles on EPO, IgG as well as the endogenous secretome following glycosyltransferase knock-out in different Chinese hamster ovary (CHO) cell lines. 26537759 2 46 theme biosafety 298:306 arg1 requirements 308:319 bioactivity and biosafety requirements 282:319 bioactivity and biosafety requirements 282:319 Consequently, drug development requires careful control of glycoforms to meet bioactivity and biosafety requirements. 26537759 7 47 theme Chinese 1129:1135 arg1 CHO 1152:1154 CHO 1152:1154 CHO 1152:1154 We use this method to predict and experimentally validate glycoprofiles on EPO, IgG as well as the endogenous secretome following glycosyltransferase knock-out in different Chinese hamster ovary (CHO) cell lines. 26537759 7 47 theme Chinese 1129:1135 arg1 ovary 1145:1149 Chinese hamster ovary 1129:1149 different Chinese hamster ovary (CHO) cell lines 1119:1166 We use this method to predict and experimentally validate glycoprofiles on EPO, IgG as well as the endogenous secretome following glycosyltransferase knock-out in different Chinese hamster ovary (CHO) cell lines. 26537759 1 48 theme critical 140:147 arg1 attribute 157:165 a critical quality attribute 138:165 a critical quality attribute of most recombinant biotherapeutics 138:201 Glycosylation is a critical quality attribute of most recombinant biotherapeutics. 26537759 1 48 theme critical 140:147 arg1 Glycosylation 121:133 Glycosylation 121:133 Glycosylation 121:133 Glycosylation is a critical quality attribute of most recombinant biotherapeutics. 26537759 6 49 theme kinetic 935:941 arg1 information 943:953 user-provided kinetic information 921:953 user-provided kinetic information 921:953 The model recapitulates the biological complexity of glycosylation, but does not require user-provided kinetic information. 26537759 7 50 theme hamster 1137:1143 arg1 CHO 1152:1154 CHO 1152:1154 CHO 1152:1154 We use this method to predict and experimentally validate glycoprofiles on EPO, IgG as well as the endogenous secretome following glycosyltransferase knock-out in different Chinese hamster ovary (CHO) cell lines. 26537759 7 50 theme hamster 1137:1143 arg1 ovary 1145:1149 Chinese hamster ovary 1129:1149 different Chinese hamster ovary (CHO) cell lines 1119:1166 We use this method to predict and experimentally validate glycoprofiles on EPO, IgG as well as the endogenous secretome following glycosyltransferase knock-out in different Chinese hamster ovary (CHO) cell lines. 26537759 1 51 theme quality 149:155 arg1 attribute 157:165 a critical quality attribute 138:165 a critical quality attribute of most recombinant biotherapeutics 138:201 Glycosylation is a critical quality attribute of most recombinant biotherapeutics. 26537759 1 51 theme quality 149:155 arg1 Glycosylation 121:133 Glycosylation 121:133 Glycosylation 121:133 Glycosylation is a critical quality attribute of most recombinant biotherapeutics. 26537759 0 52 theme low-parameter 67:79 arg1 tool 81:84 a low-parameter tool 65:84 a low-parameter tool for model-driven glycoengineering 65:118 A Markov chain model for N-linked protein glycosylation--towards a low-parameter tool for model-driven glycoengineering. 26537759 2 53 theme drug 218:221 arg1 development 223:233 drug development 218:233 drug development 218:233 Consequently, drug development requires careful control of glycoforms to meet bioactivity and biosafety requirements. 26537759 2 54 theme bioactivity 282:292 arg1 requirements 308:319 bioactivity and biosafety requirements 282:319 bioactivity and biosafety requirements 282:319 Consequently, drug development requires careful control of glycoforms to meet bioactivity and biosafety requirements. 26537759 3 55 theme complex 391:397 arg1 networks 408:415 the complex reaction networks 387:415 the complex reaction networks underlying glycosylation and the vast number of different glycans that can be synthesized in a host cell 387:520 However, glycoengineering can be extraordinarily difficult given the complex reaction networks underlying glycosylation and the vast number of different glycans that can be synthesized in a host cell. 26537759 8 56 theme mammalian 1303:1311 arg1 factories 1318:1326 mammalian cell factories 1303:1326 mammalian cell factories for biopharmaceutical production 1303:1359 Our approach offers a flexible and user-friendly platform that can serve as a basis for powerful computational engineering efforts in mammalian cell factories for biopharmaceutical production. 26537759 7 57 theme following 1076:1084 arg1 knock-out 1106:1114 the endogenous secretome following glycosyltransferase knock-out 1051:1114 the endogenous secretome following glycosyltransferase knock-out in different Chinese hamster ovary (CHO) cell lines 1051:1166 We use this method to predict and experimentally validate glycoprofiles on EPO, IgG as well as the endogenous secretome following glycosyltransferase knock-out in different Chinese hamster ovary (CHO) cell lines. 26537759 3 58 theme vast 450:453 arg1 number 455:460 the vast number 446:460 the vast number of different glycans that can be synthesized in a host cell 446:520 However, glycoengineering can be extraordinarily difficult given the complex reaction networks underlying glycosylation and the vast number of different glycans that can be synthesized in a host cell. 26537759 8 59 theme flexible 1191:1198 arg1 platform 1218:1225 a flexible and user-friendly platform 1189:1225 a flexible and user-friendly platform that can serve as a basis for powerful computational engineering efforts in mammalian cell factories for biopharmaceutical production 1189:1359 Our approach offers a flexible and user-friendly platform that can serve as a basis for powerful computational engineering efforts in mammalian cell factories for biopharmaceutical production. 26537759 8 59 theme flexible 1191:1198 arg1 basis 1247:1251 a basis 1245:1251 a basis for powerful computational engineering efforts in mammalian cell factories for biopharmaceutical production 1245:1359 Our approach offers a flexible and user-friendly platform that can serve as a basis for powerful computational engineering efforts in mammalian cell factories for biopharmaceutical production. 25805840 5 0 theme squamous 1060:1067 arg1 carcinoma 1074:1082 human oral squamous cell carcinoma 1049:1082 human oral squamous cell carcinoma 1049:1082 Recently, we documented MMP-20 expression and interaction with DSPP (another member of the SIBLING family) in human oral squamous cell carcinoma. 25805840 5 1 theme family 1038:1043 arg1 member 1016:1021 another member 1008:1021 another member of the SIBLING family 1008:1043 Recently, we documented MMP-20 expression and interaction with DSPP (another member of the SIBLING family) in human oral squamous cell carcinoma. 25805840 6 2 from DSPP 1187:1190 arg1 line 1239:1242 cell line 1234:1242 cell line 1234:1242 Here we report the expression of MMP-20, and confirm its co-expression and potential interaction with DSPP in human major salivary gland tissues and cell line using immunohistochemistry, immunofluorescence, western blot, quantitative RT-PCR, and proximity ligation assay. 25805840 6 2 from DSPP 1187:1190 arg1 tissues 1222:1228 human major salivary gland tissues 1195:1228 human major salivary gland tissues 1195:1228 Here we report the expression of MMP-20, and confirm its co-expression and potential interaction with DSPP in human major salivary gland tissues and cell line using immunohistochemistry, immunofluorescence, western blot, quantitative RT-PCR, and proximity ligation assay. 25805840 0 3 theme Interaction 62:72 arg1 Expression 0:9 Expression 0:9 Expression of Matrix Metalloproteinase (MMP)-20 and Potential Interaction with Dentin Sialophosphoprotein (DSPP) in Human Major Salivary Glands. 0:143 Expression of Matrix Metalloproteinase (MMP)-20 and Potential Interaction with Dentin Sialophosphoprotein (DSPP) in Human Major Salivary Glands. 25805840 5 4 theme cell 1069:1072 arg1 carcinoma 1074:1082 human oral squamous cell carcinoma 1049:1082 human oral squamous cell carcinoma 1049:1082 Recently, we documented MMP-20 expression and interaction with DSPP (another member of the SIBLING family) in human oral squamous cell carcinoma. 25805840 4 5 theme biological 828:837 arg1 systems 839:845 biological systems 828:845 biological systems 828:845 The SIBLING-MMP interaction was confirmed in biological systems such as the ducts of salivary glands, where all five members of the SIBLINGs are expressed. 25805840 4 5 theme biological 828:837 arg1 ducts 859:863 the ducts 855:863 the ducts of salivary glands 855:882 The SIBLING-MMP interaction was confirmed in biological systems such as the ducts of salivary glands, where all five members of the SIBLINGs are expressed. 25805840 1 6 theme Matrix 145:150 arg1 MMP-20 174:179 MMP-20 174:179 MMP-20 174:179 Matrix metalloproteinase-20 (MMP-20) expression is widely regarded as tooth-specific, with expression limited to dental hard tissues. 25805840 1 6 theme Matrix 145:150 arg1 metalloproteinase-20 152:171 Matrix metalloproteinase-20 145:171 Matrix metalloproteinase-20 (MMP-20) expression 145:191 Matrix metalloproteinase-20 (MMP-20) expression is widely regarded as tooth-specific, with expression limited to dental hard tissues. 25805840 3 7 with MMPs 675:678 arg1 MMP-3 737:741 MMP-3 737:741 MMP-3 737:741 In the mid-2000s, three members of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) were reported to bind specifically with high affinity (nM) to, and activate, three MMPs in vitro: bone sialoprotein with MMP-2; osteopontin with MMP-3; and dentin matrix protein1 with MMP-9. 25805840 3 7 with MMPs 675:678 arg1 MMP-2 713:717 MMP-2 713:717 MMP-2 713:717 In the mid-2000s, three members of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) were reported to bind specifically with high affinity (nM) to, and activate, three MMPs in vitro: bone sialoprotein with MMP-2; osteopontin with MMP-3; and dentin matrix protein1 with MMP-9. 25805840 3 7 with MMPs 675:678 arg1 MMP-9 776:780 MMP-9 776:780 MMP-9 776:780 In the mid-2000s, three members of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) were reported to bind specifically with high affinity (nM) to, and activate, three MMPs in vitro: bone sialoprotein with MMP-2; osteopontin with MMP-3; and dentin matrix protein1 with MMP-9. 25805840 1 8 theme limited 247:253 arg1 expression 236:245 expression 236:245 expression limited to dental hard tissues 236:276 Matrix metalloproteinase-20 (MMP-20) expression is widely regarded as tooth-specific, with expression limited to dental hard tissues. 25805840 6 9 theme quantitative 1306:1317 arg1 RT-PCR 1319:1324 quantitative RT-PCR 1306:1324 quantitative RT-PCR 1306:1324 Here we report the expression of MMP-20, and confirm its co-expression and potential interaction with DSPP in human major salivary gland tissues and cell line using immunohistochemistry, immunofluorescence, western blot, quantitative RT-PCR, and proximity ligation assay. 25805840 0 10 from Expression 0:9 arg1 Glands 137:142 Human Major Salivary Glands 116:142 Human Major Salivary Glands 116:142 Expression of Matrix Metalloproteinase (MMP)-20 and Potential Interaction with Dentin Sialophosphoprotein (DSPP) in Human Major Salivary Glands. 25805840 6 11 theme salivary 1207:1214 arg1 tissues 1222:1228 human major salivary gland tissues 1195:1228 human major salivary gland tissues 1195:1228 Here we report the expression of MMP-20, and confirm its co-expression and potential interaction with DSPP in human major salivary gland tissues and cell line using immunohistochemistry, immunofluorescence, western blot, quantitative RT-PCR, and proximity ligation assay. 25805840 0 12 with Interaction 62:72 arg1 Sialophosphoprotein 86:104 Dentin Sialophosphoprotein 79:104 Dentin Sialophosphoprotein (DSPP) 79:111 Expression of Matrix Metalloproteinase (MMP)-20 and Potential Interaction with Dentin Sialophosphoprotein (DSPP) in Human Major Salivary Glands. 25805840 0 12 with Interaction 62:72 arg1 DSPP 107:110 DSPP 107:110 DSPP 107:110 Expression of Matrix Metalloproteinase (MMP)-20 and Potential Interaction with Dentin Sialophosphoprotein (DSPP) in Human Major Salivary Glands. 25805840 2 13 dep process 350:356 arg1 Necessary 279:287 Necessary 279:287 Necessary 279:287 Necessary for sound enamel formation, MMP-20 and MMP-2 proteolytically process dentin sialophosphoprotein (DSPP) into dentin sialoprotein, dentin phosphoprotein, and dentin glycoprotein during tooth formation. 25805840 7 14 theme oxidation 1503:1511 arg1 byproducts 1513:1522 oxidation byproducts 1503:1522 oxidation byproducts in metabolically active duct epithelial systems 1503:1570 This report reinforces our earlier suggestion that the SIBLING-MMP complexes may be involved in the turnover of extracellular proteins damaged by oxidation byproducts in metabolically active duct epithelial systems. 25805840 0 15 theme Dentin 79:84 arg1 Sialophosphoprotein 86:104 Dentin Sialophosphoprotein 79:104 Dentin Sialophosphoprotein (DSPP) 79:111 Expression of Matrix Metalloproteinase (MMP)-20 and Potential Interaction with Dentin Sialophosphoprotein (DSPP) in Human Major Salivary Glands. 25805840 0 15 theme Dentin 79:84 arg1 DSPP 107:110 DSPP 107:110 DSPP 107:110 Expression of Matrix Metalloproteinase (MMP)-20 and Potential Interaction with Dentin Sialophosphoprotein (DSPP) in Human Major Salivary Glands. 25805840 3 16 theme bone 690:693 arg1 sialoprotein 695:706 bone sialoprotein 690:706 bone sialoprotein with MMP-2 690:717 In the mid-2000s, three members of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) were reported to bind specifically with high affinity (nM) to, and activate, three MMPs in vitro: bone sialoprotein with MMP-2; osteopontin with MMP-3; and dentin matrix protein1 with MMP-9. 25805840 6 17 theme major 1201:1205 arg1 tissues 1222:1228 human major salivary gland tissues 1195:1228 human major salivary gland tissues 1195:1228 Here we report the expression of MMP-20, and confirm its co-expression and potential interaction with DSPP in human major salivary gland tissues and cell line using immunohistochemistry, immunofluorescence, western blot, quantitative RT-PCR, and proximity ligation assay. 25805840 5 18 dep DSPP 1002:1005 arg1 member 1016:1021 another member 1008:1021 another member of the SIBLING family 1008:1043 Recently, we documented MMP-20 expression and interaction with DSPP (another member of the SIBLING family) in human oral squamous cell carcinoma. 25805840 3 19 theme ligand 551:556 arg1 glycoproteins 567:579 the small integrin-binding ligand N-linked glycoproteins 524:579 the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) 524:590 In the mid-2000s, three members of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) were reported to bind specifically with high affinity (nM) to, and activate, three MMPs in vitro: bone sialoprotein with MMP-2; osteopontin with MMP-3; and dentin matrix protein1 with MMP-9. 25805840 3 19 theme ligand 551:556 arg1 SIBLINGs 582:589 SIBLINGs 582:589 SIBLINGs 582:589 In the mid-2000s, three members of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) were reported to bind specifically with high affinity (nM) to, and activate, three MMPs in vitro: bone sialoprotein with MMP-2; osteopontin with MMP-3; and dentin matrix protein1 with MMP-9. 25805840 1 20 theme dental 258:263 arg1 tissues 270:276 dental hard tissues 258:276 dental hard tissues 258:276 Matrix metalloproteinase-20 (MMP-20) expression is widely regarded as tooth-specific, with expression limited to dental hard tissues. 25805840 7 21 theme SIBLING-MMP 1412:1422 arg1 complexes 1424:1432 the SIBLING-MMP complexes 1408:1432 the SIBLING-MMP complexes 1408:1432 This report reinforces our earlier suggestion that the SIBLING-MMP complexes may be involved in the turnover of extracellular proteins damaged by oxidation byproducts in metabolically active duct epithelial systems. 25805840 6 22 theme human 1195:1199 arg1 tissues 1222:1228 human major salivary gland tissues 1195:1228 human major salivary gland tissues 1195:1228 Here we report the expression of MMP-20, and confirm its co-expression and potential interaction with DSPP in human major salivary gland tissues and cell line using immunohistochemistry, immunofluorescence, western blot, quantitative RT-PCR, and proximity ligation assay. 25805840 1 23 theme metalloproteinase-20 152:171 arg1 tooth-specific 215:228 tooth-specific 215:228 tooth-specific 215:228 Matrix metalloproteinase-20 (MMP-20) expression is widely regarded as tooth-specific, with expression limited to dental hard tissues. 25805840 1 23 theme metalloproteinase-20 152:171 arg1 expression 182:191 Matrix metalloproteinase-20 (MMP-20) expression 145:191 Matrix metalloproteinase-20 (MMP-20) expression 145:191 Matrix metalloproteinase-20 (MMP-20) expression is widely regarded as tooth-specific, with expression limited to dental hard tissues. 25805840 5 24 with expression 970:979 arg1 DSPP 1002:1005 DSPP 1002:1005 DSPP (another member of the SIBLING family) in human oral squamous cell carcinoma 1002:1082 Recently, we documented MMP-20 expression and interaction with DSPP (another member of the SIBLING family) in human oral squamous cell carcinoma. 25805840 5 25 theme oral 1055:1058 arg1 carcinoma 1074:1082 human oral squamous cell carcinoma 1049:1082 human oral squamous cell carcinoma 1049:1082 Recently, we documented MMP-20 expression and interaction with DSPP (another member of the SIBLING family) in human oral squamous cell carcinoma. 25805840 3 26 theme small 528:532 arg1 glycoproteins 567:579 the small integrin-binding ligand N-linked glycoproteins 524:579 the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) 524:590 In the mid-2000s, three members of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) were reported to bind specifically with high affinity (nM) to, and activate, three MMPs in vitro: bone sialoprotein with MMP-2; osteopontin with MMP-3; and dentin matrix protein1 with MMP-9. 25805840 3 26 theme small 528:532 arg1 SIBLINGs 582:589 SIBLINGs 582:589 SIBLINGs 582:589 In the mid-2000s, three members of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) were reported to bind specifically with high affinity (nM) to, and activate, three MMPs in vitro: bone sialoprotein with MMP-2; osteopontin with MMP-3; and dentin matrix protein1 with MMP-9. 25805840 2 27 theme dentin 445:450 arg1 glycoprotein 452:463 dentin glycoprotein 445:463 dentin glycoprotein 445:463 Necessary for sound enamel formation, MMP-20 and MMP-2 proteolytically process dentin sialophosphoprotein (DSPP) into dentin sialoprotein, dentin phosphoprotein, and dentin glycoprotein during tooth formation. 25805840 5 28 theme human 1049:1053 arg1 carcinoma 1074:1082 human oral squamous cell carcinoma 1049:1082 human oral squamous cell carcinoma 1049:1082 Recently, we documented MMP-20 expression and interaction with DSPP (another member of the SIBLING family) in human oral squamous cell carcinoma. 25805840 3 29 link N-linked 558:565 arg1 glycoproteins 567:579 the small integrin-binding ligand N-linked glycoproteins 524:579 the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) 524:590 In the mid-2000s, three members of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) were reported to bind specifically with high affinity (nM) to, and activate, three MMPs in vitro: bone sialoprotein with MMP-2; osteopontin with MMP-3; and dentin matrix protein1 with MMP-9. 25805840 3 29 link N-linked 558:565 arg1 SIBLINGs 582:589 SIBLINGs 582:589 SIBLINGs 582:589 In the mid-2000s, three members of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) were reported to bind specifically with high affinity (nM) to, and activate, three MMPs in vitro: bone sialoprotein with MMP-2; osteopontin with MMP-3; and dentin matrix protein1 with MMP-9. 25805840 7 30 theme active 1541:1546 arg1 systems 1564:1570 metabolically active duct epithelial systems 1527:1570 metabolically active duct epithelial systems 1527:1570 This report reinforces our earlier suggestion that the SIBLING-MMP complexes may be involved in the turnover of extracellular proteins damaged by oxidation byproducts in metabolically active duct epithelial systems. 25805840 1 31 theme hard 265:268 arg1 tissues 270:276 dental hard tissues 258:276 dental hard tissues 258:276 Matrix metalloproteinase-20 (MMP-20) expression is widely regarded as tooth-specific, with expression limited to dental hard tissues. 25805840 3 32 from osteopontin 720:730 arg1 vitro 683:687 vitro 683:687 vitro 683:687 In the mid-2000s, three members of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) were reported to bind specifically with high affinity (nM) to, and activate, three MMPs in vitro: bone sialoprotein with MMP-2; osteopontin with MMP-3; and dentin matrix protein1 with MMP-9. 25805840 2 33 theme enamel 299:304 arg1 formation 306:314 sound enamel formation 293:314 sound enamel formation 293:314 Necessary for sound enamel formation, MMP-20 and MMP-2 proteolytically process dentin sialophosphoprotein (DSPP) into dentin sialoprotein, dentin phosphoprotein, and dentin glycoprotein during tooth formation. 25805840 6 34 theme gland 1216:1220 arg1 tissues 1222:1228 human major salivary gland tissues 1195:1228 human major salivary gland tissues 1195:1228 Here we report the expression of MMP-20, and confirm its co-expression and potential interaction with DSPP in human major salivary gland tissues and cell line using immunohistochemistry, immunofluorescence, western blot, quantitative RT-PCR, and proximity ligation assay. 25805840 0 35 theme Metalloproteinase 21:37 arg1 Expression 0:9 Expression 0:9 Expression of Matrix Metalloproteinase (MMP)-20 and Potential Interaction with Dentin Sialophosphoprotein (DSPP) in Human Major Salivary Glands. 0:143 Expression of Matrix Metalloproteinase (MMP)-20 and Potential Interaction with Dentin Sialophosphoprotein (DSPP) in Human Major Salivary Glands. 25805840 6 36 theme cell 1234:1237 arg1 line 1239:1242 cell line 1234:1242 cell line 1234:1242 Here we report the expression of MMP-20, and confirm its co-expression and potential interaction with DSPP in human major salivary gland tissues and cell line using immunohistochemistry, immunofluorescence, western blot, quantitative RT-PCR, and proximity ligation assay. 25805840 6 37 theme western 1292:1298 arg1 blot 1300:1303 western blot 1292:1303 western blot 1292:1303 Here we report the expression of MMP-20, and confirm its co-expression and potential interaction with DSPP in human major salivary gland tissues and cell line using immunohistochemistry, immunofluorescence, western blot, quantitative RT-PCR, and proximity ligation assay. 25805840 3 38 with osteopontin 720:730 arg1 MMP-3 737:741 MMP-3 737:741 MMP-3 737:741 In the mid-2000s, three members of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) were reported to bind specifically with high affinity (nM) to, and activate, three MMPs in vitro: bone sialoprotein with MMP-2; osteopontin with MMP-3; and dentin matrix protein1 with MMP-9. 25805840 3 38 with osteopontin 720:730 arg1 MMP-2 713:717 MMP-2 713:717 MMP-2 713:717 In the mid-2000s, three members of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) were reported to bind specifically with high affinity (nM) to, and activate, three MMPs in vitro: bone sialoprotein with MMP-2; osteopontin with MMP-3; and dentin matrix protein1 with MMP-9. 25805840 3 38 with osteopontin 720:730 arg1 MMP-9 776:780 MMP-9 776:780 MMP-9 776:780 In the mid-2000s, three members of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) were reported to bind specifically with high affinity (nM) to, and activate, three MMPs in vitro: bone sialoprotein with MMP-2; osteopontin with MMP-3; and dentin matrix protein1 with MMP-9. 25805840 2 39 theme sound 293:297 arg1 formation 306:314 sound enamel formation 293:314 sound enamel formation 293:314 Necessary for sound enamel formation, MMP-20 and MMP-2 proteolytically process dentin sialophosphoprotein (DSPP) into dentin sialoprotein, dentin phosphoprotein, and dentin glycoprotein during tooth formation. 25805840 2 40 theme dentin 418:423 arg1 phosphoprotein 425:438 dentin phosphoprotein 418:438 dentin phosphoprotein 418:438 Necessary for sound enamel formation, MMP-20 and MMP-2 proteolytically process dentin sialophosphoprotein (DSPP) into dentin sialoprotein, dentin phosphoprotein, and dentin glycoprotein during tooth formation. 25805840 0 41 theme Matrix 14:19 arg1 MMP 40:42 MMP 40:42 MMP 40:42 Expression of Matrix Metalloproteinase (MMP)-20 and Potential Interaction with Dentin Sialophosphoprotein (DSPP) in Human Major Salivary Glands. 25805840 0 41 theme Matrix 14:19 arg1 Metalloproteinase 21:37 Matrix Metalloproteinase (MMP)-20 14:46 Matrix Metalloproteinase (MMP)-20 14:46 Expression of Matrix Metalloproteinase (MMP)-20 and Potential Interaction with Dentin Sialophosphoprotein (DSPP) in Human Major Salivary Glands. 25805840 4 42 theme glands 877:882 arg1 ducts 859:863 the ducts 855:863 the ducts of salivary glands 855:882 The SIBLING-MMP interaction was confirmed in biological systems such as the ducts of salivary glands, where all five members of the SIBLINGs are expressed. 25805840 6 43 theme MMP-20 1118:1123 arg1 expression 1104:1113 the expression 1100:1113 the expression of MMP-20 1100:1123 Here we report the expression of MMP-20, and confirm its co-expression and potential interaction with DSPP in human major salivary gland tissues and cell line using immunohistochemistry, immunofluorescence, western blot, quantitative RT-PCR, and proximity ligation assay. 25805840 3 44 theme glycoproteins 567:579 arg1 members 513:519 three members 507:519 three members of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) 507:590 In the mid-2000s, three members of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) were reported to bind specifically with high affinity (nM) to, and activate, three MMPs in vitro: bone sialoprotein with MMP-2; osteopontin with MMP-3; and dentin matrix protein1 with MMP-9. 25805840 6 45 theme proximity 1331:1339 arg1 assay 1350:1354 proximity ligation assay 1331:1354 proximity ligation assay 1331:1354 Here we report the expression of MMP-20, and confirm its co-expression and potential interaction with DSPP in human major salivary gland tissues and cell line using immunohistochemistry, immunofluorescence, western blot, quantitative RT-PCR, and proximity ligation assay. 25805840 0 46 theme Major 122:126 arg1 Glands 137:142 Human Major Salivary Glands 116:142 Human Major Salivary Glands 116:142 Expression of Matrix Metalloproteinase (MMP)-20 and Potential Interaction with Dentin Sialophosphoprotein (DSPP) in Human Major Salivary Glands. 25805840 5 47 theme MMP-20 963:968 arg1 expression 970:979 MMP-20 expression 963:979 MMP-20 expression 963:979 Recently, we documented MMP-20 expression and interaction with DSPP (another member of the SIBLING family) in human oral squamous cell carcinoma. 25805840 5 48 from DSPP 1002:1005 arg1 carcinoma 1074:1082 human oral squamous cell carcinoma 1049:1082 human oral squamous cell carcinoma 1049:1082 Recently, we documented MMP-20 expression and interaction with DSPP (another member of the SIBLING family) in human oral squamous cell carcinoma. 25805840 5 49 with interaction 985:995 arg1 DSPP 1002:1005 DSPP 1002:1005 DSPP (another member of the SIBLING family) in human oral squamous cell carcinoma 1002:1082 Recently, we documented MMP-20 expression and interaction with DSPP (another member of the SIBLING family) in human oral squamous cell carcinoma. 25805840 2 50 theme tooth 472:476 arg1 formation 478:486 tooth formation 472:486 tooth formation 472:486 Necessary for sound enamel formation, MMP-20 and MMP-2 proteolytically process dentin sialophosphoprotein (DSPP) into dentin sialoprotein, dentin phosphoprotein, and dentin glycoprotein during tooth formation. 25805840 7 51 dep suggestion 1392:1401 arg1 involved 1441:1448 involved 1441:1448 may be involved in the turnover of extracellular proteins damaged by oxidation byproducts in metabolically active duct epithelial systems 1434:1570 This report reinforces our earlier suggestion that the SIBLING-MMP complexes may be involved in the turnover of extracellular proteins damaged by oxidation byproducts in metabolically active duct epithelial systems. 25805840 0 52 theme Human 116:120 arg1 Glands 137:142 Human Major Salivary Glands 116:142 Human Major Salivary Glands 116:142 Expression of Matrix Metalloproteinase (MMP)-20 and Potential Interaction with Dentin Sialophosphoprotein (DSPP) in Human Major Salivary Glands. 25805840 7 53 theme extracellular 1469:1481 arg1 proteins 1483:1490 extracellular proteins 1469:1490 extracellular proteins damaged by oxidation byproducts in metabolically active duct epithelial systems 1469:1570 This report reinforces our earlier suggestion that the SIBLING-MMP complexes may be involved in the turnover of extracellular proteins damaged by oxidation byproducts in metabolically active duct epithelial systems. 25805840 6 54 theme potential 1160:1168 arg1 interaction 1170:1180 potential interaction 1160:1180 potential interaction with DSPP in human major salivary gland tissues and cell line using immunohistochemistry, immunofluorescence, western blot, quantitative RT-PCR, and proximity ligation assay 1160:1354 Here we report the expression of MMP-20, and confirm its co-expression and potential interaction with DSPP in human major salivary gland tissues and cell line using immunohistochemistry, immunofluorescence, western blot, quantitative RT-PCR, and proximity ligation assay. 25805840 0 55 with Metalloproteinase 21:37 arg1 Sialophosphoprotein 86:104 Dentin Sialophosphoprotein 79:104 Dentin Sialophosphoprotein (DSPP) 79:111 Expression of Matrix Metalloproteinase (MMP)-20 and Potential Interaction with Dentin Sialophosphoprotein (DSPP) in Human Major Salivary Glands. 25805840 0 55 with Metalloproteinase 21:37 arg1 DSPP 107:110 DSPP 107:110 DSPP 107:110 Expression of Matrix Metalloproteinase (MMP)-20 and Potential Interaction with Dentin Sialophosphoprotein (DSPP) in Human Major Salivary Glands. 25805840 2 56 theme dentin 397:402 arg1 sialoprotein 404:415 dentin sialoprotein 397:415 dentin sialoprotein 397:415 Necessary for sound enamel formation, MMP-20 and MMP-2 proteolytically process dentin sialophosphoprotein (DSPP) into dentin sialoprotein, dentin phosphoprotein, and dentin glycoprotein during tooth formation. 25805840 3 57 from MMPs 675:678 arg1 vitro 683:687 vitro 683:687 vitro 683:687 In the mid-2000s, three members of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) were reported to bind specifically with high affinity (nM) to, and activate, three MMPs in vitro: bone sialoprotein with MMP-2; osteopontin with MMP-3; and dentin matrix protein1 with MMP-9. 25805840 7 58 theme proteins 1483:1490 arg1 turnover 1457:1464 the turnover 1453:1464 the turnover of extracellular proteins damaged by oxidation byproducts in metabolically active duct epithelial systems 1453:1570 This report reinforces our earlier suggestion that the SIBLING-MMP complexes may be involved in the turnover of extracellular proteins damaged by oxidation byproducts in metabolically active duct epithelial systems. 25805840 5 59 theme SIBLING 1030:1036 arg1 family 1038:1043 the SIBLING family 1026:1043 the SIBLING family 1026:1043 Recently, we documented MMP-20 expression and interaction with DSPP (another member of the SIBLING family) in human oral squamous cell carcinoma. 25805840 2 60 gly glycoprotein 452:463 arg1 glycoprotein 452:463 dentin glycoprotein 445:463 dentin glycoprotein 445:463 Necessary for sound enamel formation, MMP-20 and MMP-2 proteolytically process dentin sialophosphoprotein (DSPP) into dentin sialoprotein, dentin phosphoprotein, and dentin glycoprotein during tooth formation. 25805840 4 61 theme salivary 868:875 arg1 glands 877:882 salivary glands 868:882 salivary glands 868:882 The SIBLING-MMP interaction was confirmed in biological systems such as the ducts of salivary glands, where all five members of the SIBLINGs are expressed. 25805840 7 62 from byproducts 1513:1522 arg1 systems 1564:1570 metabolically active duct epithelial systems 1527:1570 metabolically active duct epithelial systems 1527:1570 This report reinforces our earlier suggestion that the SIBLING-MMP complexes may be involved in the turnover of extracellular proteins damaged by oxidation byproducts in metabolically active duct epithelial systems. 25805840 6 63 theme ligation 1341:1348 arg1 assay 1350:1354 proximity ligation assay 1331:1354 proximity ligation assay 1331:1354 Here we report the expression of MMP-20, and confirm its co-expression and potential interaction with DSPP in human major salivary gland tissues and cell line using immunohistochemistry, immunofluorescence, western blot, quantitative RT-PCR, and proximity ligation assay. 25805840 0 64 theme Salivary 128:135 arg1 Glands 137:142 Human Major Salivary Glands 116:142 Human Major Salivary Glands 116:142 Expression of Matrix Metalloproteinase (MMP)-20 and Potential Interaction with Dentin Sialophosphoprotein (DSPP) in Human Major Salivary Glands. 25805840 6 65 with interaction 1170:1180 arg1 DSPP 1187:1190 DSPP 1187:1190 DSPP in human major salivary gland tissues and cell line using immunohistochemistry, immunofluorescence, western blot, quantitative RT-PCR, and proximity ligation assay 1187:1354 Here we report the expression of MMP-20, and confirm its co-expression and potential interaction with DSPP in human major salivary gland tissues and cell line using immunohistochemistry, immunofluorescence, western blot, quantitative RT-PCR, and proximity ligation assay. 25805840 3 66 from protein1 762:769 arg1 vitro 683:687 vitro 683:687 vitro 683:687 In the mid-2000s, three members of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) were reported to bind specifically with high affinity (nM) to, and activate, three MMPs in vitro: bone sialoprotein with MMP-2; osteopontin with MMP-3; and dentin matrix protein1 with MMP-9. 25805840 3 67 gly glycoproteins 567:579 arg1 glycoproteins 567:579 the small integrin-binding ligand N-linked glycoproteins 524:579 the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) 524:590 In the mid-2000s, three members of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) were reported to bind specifically with high affinity (nM) to, and activate, three MMPs in vitro: bone sialoprotein with MMP-2; osteopontin with MMP-3; and dentin matrix protein1 with MMP-9. 25805840 3 67 gly glycoproteins 567:579 arg1 SIBLINGs 582:589 SIBLINGs 582:589 SIBLINGs 582:589 In the mid-2000s, three members of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) were reported to bind specifically with high affinity (nM) to, and activate, three MMPs in vitro: bone sialoprotein with MMP-2; osteopontin with MMP-3; and dentin matrix protein1 with MMP-9. 25805840 3 68 theme N-linked 558:565 arg1 glycoproteins 567:579 the small integrin-binding ligand N-linked glycoproteins 524:579 the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) 524:590 In the mid-2000s, three members of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) were reported to bind specifically with high affinity (nM) to, and activate, three MMPs in vitro: bone sialoprotein with MMP-2; osteopontin with MMP-3; and dentin matrix protein1 with MMP-9. 25805840 3 68 theme N-linked 558:565 arg1 SIBLINGs 582:589 SIBLINGs 582:589 SIBLINGs 582:589 In the mid-2000s, three members of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) were reported to bind specifically with high affinity (nM) to, and activate, three MMPs in vitro: bone sialoprotein with MMP-2; osteopontin with MMP-3; and dentin matrix protein1 with MMP-9. 25805840 7 69 theme epithelial 1553:1562 arg1 systems 1564:1570 metabolically active duct epithelial systems 1527:1570 metabolically active duct epithelial systems 1527:1570 This report reinforces our earlier suggestion that the SIBLING-MMP complexes may be involved in the turnover of extracellular proteins damaged by oxidation byproducts in metabolically active duct epithelial systems. 25805840 3 70 theme high 632:635 arg1 nM 647:648 nM 647:648 nM 647:648 In the mid-2000s, three members of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) were reported to bind specifically with high affinity (nM) to, and activate, three MMPs in vitro: bone sialoprotein with MMP-2; osteopontin with MMP-3; and dentin matrix protein1 with MMP-9. 25805840 3 70 theme high 632:635 arg1 affinity 637:644 high affinity 632:644 high affinity (nM) 632:649 In the mid-2000s, three members of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) were reported to bind specifically with high affinity (nM) to, and activate, three MMPs in vitro: bone sialoprotein with MMP-2; osteopontin with MMP-3; and dentin matrix protein1 with MMP-9. 25805840 6 71 with co-expression 1142:1154 arg1 DSPP 1187:1190 DSPP 1187:1190 DSPP in human major salivary gland tissues and cell line using immunohistochemistry, immunofluorescence, western blot, quantitative RT-PCR, and proximity ligation assay 1187:1354 Here we report the expression of MMP-20, and confirm its co-expression and potential interaction with DSPP in human major salivary gland tissues and cell line using immunohistochemistry, immunofluorescence, western blot, quantitative RT-PCR, and proximity ligation assay. 25805840 0 72 theme Potential 52:60 arg1 Interaction 62:72 Potential Interaction 52:72 Potential Interaction with Dentin Sialophosphoprotein (DSPP) 52:111 Expression of Matrix Metalloproteinase (MMP)-20 and Potential Interaction with Dentin Sialophosphoprotein (DSPP) in Human Major Salivary Glands. 25805840 7 73 theme earlier 1384:1390 arg1 suggestion 1392:1401 our earlier suggestion 1380:1401 our earlier suggestion that the SIBLING-MMP complexes may be involved in the turnover of extracellular proteins damaged by oxidation byproducts in metabolically active duct epithelial systems 1380:1570 This report reinforces our earlier suggestion that the SIBLING-MMP complexes may be involved in the turnover of extracellular proteins damaged by oxidation byproducts in metabolically active duct epithelial systems. 25805840 4 74 theme SIBLING-MMP 787:797 arg1 interaction 799:809 The SIBLING-MMP interaction 783:809 The SIBLING-MMP interaction 783:809 The SIBLING-MMP interaction was confirmed in biological systems such as the ducts of salivary glands, where all five members of the SIBLINGs are expressed. 25805840 7 75 theme duct 1548:1551 arg1 systems 1564:1570 metabolically active duct epithelial systems 1527:1570 metabolically active duct epithelial systems 1527:1570 This report reinforces our earlier suggestion that the SIBLING-MMP complexes may be involved in the turnover of extracellular proteins damaged by oxidation byproducts in metabolically active duct epithelial systems. 25805840 3 76 with sialoprotein 695:706 arg1 MMP-3 737:741 MMP-3 737:741 MMP-3 737:741 In the mid-2000s, three members of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) were reported to bind specifically with high affinity (nM) to, and activate, three MMPs in vitro: bone sialoprotein with MMP-2; osteopontin with MMP-3; and dentin matrix protein1 with MMP-9. 25805840 3 76 with sialoprotein 695:706 arg1 MMP-2 713:717 MMP-2 713:717 MMP-2 713:717 In the mid-2000s, three members of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) were reported to bind specifically with high affinity (nM) to, and activate, three MMPs in vitro: bone sialoprotein with MMP-2; osteopontin with MMP-3; and dentin matrix protein1 with MMP-9. 25805840 3 76 with sialoprotein 695:706 arg1 MMP-9 776:780 MMP-9 776:780 MMP-9 776:780 In the mid-2000s, three members of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) were reported to bind specifically with high affinity (nM) to, and activate, three MMPs in vitro: bone sialoprotein with MMP-2; osteopontin with MMP-3; and dentin matrix protein1 with MMP-9. 25805840 3 77 theme dentin 748:753 arg1 protein1 762:769 dentin matrix protein1 748:769 dentin matrix protein1 with MMP-9 748:780 In the mid-2000s, three members of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) were reported to bind specifically with high affinity (nM) to, and activate, three MMPs in vitro: bone sialoprotein with MMP-2; osteopontin with MMP-3; and dentin matrix protein1 with MMP-9. 25805840 4 78 theme SIBLINGs 915:922 arg1 members 900:906 all five members 891:906 all five members of the SIBLINGs 891:922 The SIBLING-MMP interaction was confirmed in biological systems such as the ducts of salivary glands, where all five members of the SIBLINGs are expressed. 25805840 3 79 theme integrin-binding 534:549 arg1 glycoproteins 567:579 the small integrin-binding ligand N-linked glycoproteins 524:579 the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) 524:590 In the mid-2000s, three members of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) were reported to bind specifically with high affinity (nM) to, and activate, three MMPs in vitro: bone sialoprotein with MMP-2; osteopontin with MMP-3; and dentin matrix protein1 with MMP-9. 25805840 3 79 theme integrin-binding 534:549 arg1 SIBLINGs 582:589 SIBLINGs 582:589 SIBLINGs 582:589 In the mid-2000s, three members of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) were reported to bind specifically with high affinity (nM) to, and activate, three MMPs in vitro: bone sialoprotein with MMP-2; osteopontin with MMP-3; and dentin matrix protein1 with MMP-9. 25805840 3 80 from sialoprotein 695:706 arg1 vitro 683:687 vitro 683:687 vitro 683:687 In the mid-2000s, three members of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) were reported to bind specifically with high affinity (nM) to, and activate, three MMPs in vitro: bone sialoprotein with MMP-2; osteopontin with MMP-3; and dentin matrix protein1 with MMP-9. 25805840 3 81 with protein1 762:769 arg1 MMP-3 737:741 MMP-3 737:741 MMP-3 737:741 In the mid-2000s, three members of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) were reported to bind specifically with high affinity (nM) to, and activate, three MMPs in vitro: bone sialoprotein with MMP-2; osteopontin with MMP-3; and dentin matrix protein1 with MMP-9. 25805840 3 81 with protein1 762:769 arg1 MMP-2 713:717 MMP-2 713:717 MMP-2 713:717 In the mid-2000s, three members of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) were reported to bind specifically with high affinity (nM) to, and activate, three MMPs in vitro: bone sialoprotein with MMP-2; osteopontin with MMP-3; and dentin matrix protein1 with MMP-9. 25805840 3 81 with protein1 762:769 arg1 MMP-9 776:780 MMP-9 776:780 MMP-9 776:780 In the mid-2000s, three members of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) were reported to bind specifically with high affinity (nM) to, and activate, three MMPs in vitro: bone sialoprotein with MMP-2; osteopontin with MMP-3; and dentin matrix protein1 with MMP-9. 25805840 2 82 theme dentin 358:363 arg1 DSPP 386:389 DSPP 386:389 DSPP 386:389 Necessary for sound enamel formation, MMP-20 and MMP-2 proteolytically process dentin sialophosphoprotein (DSPP) into dentin sialoprotein, dentin phosphoprotein, and dentin glycoprotein during tooth formation. 25805840 2 82 theme dentin 358:363 arg1 sialophosphoprotein 365:383 dentin sialophosphoprotein 358:383 dentin sialophosphoprotein (DSPP) 358:390 Necessary for sound enamel formation, MMP-20 and MMP-2 proteolytically process dentin sialophosphoprotein (DSPP) into dentin sialoprotein, dentin phosphoprotein, and dentin glycoprotein during tooth formation. 25805840 3 83 theme matrix 755:760 arg1 protein1 762:769 dentin matrix protein1 748:769 dentin matrix protein1 with MMP-9 748:780 In the mid-2000s, three members of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) were reported to bind specifically with high affinity (nM) to, and activate, three MMPs in vitro: bone sialoprotein with MMP-2; osteopontin with MMP-3; and dentin matrix protein1 with MMP-9. 25471383 6 0 theme thioredoxin 1064:1074 arg1 domains 1087:1093 three tandem thioredoxin (Trx)-like domains 1051:1093 three tandem thioredoxin (Trx)-like domains 1051:1093 Based on bioinformatics analyses, the folding-sensor region of UGGT was predicted to harbour three tandem thioredoxin (Trx)-like domains, which are often found in proteins involved in ER quality control. 25471383 8 1 theme UGGT 1497:1500 arg1 mechanism 1484:1492 the folding-sensor mechanism 1465:1492 the folding-sensor mechanism of UGGT 1465:1500 Our structural data suggest that this hydrophobic patch is involved in intermolecular interactions, thereby contributing to the folding-sensor mechanism of UGGT. 25471383 2 2 theme N-linked 372:379 arg1 intermediates 388:400 N-linked glycan intermediates 372:400 N-linked glycan intermediates displayed on proteins 372:422 In this system, a series of N-linked glycan intermediates displayed on proteins serve as quality tags. 25471383 5 3 theme UGGT 952:955 arg1 study 943:947 a structural study 930:947 a structural study of UGGT 930:955 To elucidate the folding-sensor mechanism in the ER, we performed a structural study of UGGT. 25471383 7 4 theme Trx-like 1234:1241 arg1 domain 1243:1248 the third Trx-like domain 1224:1248 the third Trx-like domain 1224:1248 Furthermore, we determined the three-dimensional structure of the third Trx-like domain, which exhibits an extensive hydrophobic patch concealed by its flexible C-terminal helix. 25471383 0 5 theme crystal 98:104 arg1 structure 106:114 crystal structure 98:114 Structural insight into substrate recognition by the endoplasmic reticulum folding-sensor enzyme: crystal structure of third thioredoxin-like domain of UDP-glucose:glycoprotein glucosyltransferase. 0:196 Structural insight into substrate recognition by the endoplasmic reticulum folding-sensor enzyme: crystal structure of third thioredoxin-like domain of UDP-glucose:glycoprotein glucosyltransferase. 25471383 2 6 link N-linked 372:379 arg1 intermediates 388:400 N-linked glycan intermediates 372:400 N-linked glycan intermediates displayed on proteins 372:422 In this system, a series of N-linked glycan intermediates displayed on proteins serve as quality tags. 25471383 8 7 theme hydrophobic 1379:1389 arg1 patch 1391:1395 this hydrophobic patch 1374:1395 this hydrophobic patch 1374:1395 Our structural data suggest that this hydrophobic patch is involved in intermolecular interactions, thereby contributing to the folding-sensor mechanism of UGGT. 25471383 7 8 theme extensive 1269:1277 arg1 patch 1291:1295 an extensive hydrophobic patch 1266:1295 an extensive hydrophobic patch concealed by its flexible C-terminal helix 1266:1338 Furthermore, we determined the three-dimensional structure of the third Trx-like domain, which exhibits an extensive hydrophobic patch concealed by its flexible C-terminal helix. 25471383 1 9 theme efficient 290:298 arg1 folding 300:306 the efficient folding 286:306 the efficient folding of newly synthesized glycoproteins 286:341 The endoplasmic reticulum (ER) possesses a protein quality control system that supports the efficient folding of newly synthesized glycoproteins. 25471383 0 10 theme third 119:123 arg1 UDP-glucose 152:162 UDP-glucose 152:162 UDP-glucose 152:162 Structural insight into substrate recognition by the endoplasmic reticulum folding-sensor enzyme: crystal structure of third thioredoxin-like domain of UDP-glucose:glycoprotein glucosyltransferase. 25471383 0 10 theme third 119:123 arg1 domain 142:147 third thioredoxin-like domain 119:147 third thioredoxin-like domain of UDP-glucose 119:162 Structural insight into substrate recognition by the endoplasmic reticulum folding-sensor enzyme: crystal structure of third thioredoxin-like domain of UDP-glucose:glycoprotein glucosyltransferase. 25471383 6 11 located found 1112:1116 arg1 proteins 1121:1128 proteins 1121:1128 proteins involved in ER quality control 1121:1159 Based on bioinformatics analyses, the folding-sensor region of UGGT was predicted to harbour three tandem thioredoxin (Trx)-like domains, which are often found in proteins involved in ER quality control. 25471383 6 11 located found 1112:1116 arg2 domains 1087:1093 three tandem thioredoxin (Trx)-like domains 1051:1093 three tandem thioredoxin (Trx)-like domains 1051:1093 Based on bioinformatics analyses, the folding-sensor region of UGGT was predicted to harbour three tandem thioredoxin (Trx)-like domains, which are often found in proteins involved in ER quality control. 25471383 7 12 theme three-dimensional 1193:1209 arg1 structure 1211:1219 the three-dimensional structure 1189:1219 the three-dimensional structure of the third Trx-like domain, which exhibits an extensive hydrophobic patch concealed by its flexible C-terminal helix 1189:1338 Furthermore, we determined the three-dimensional structure of the third Trx-like domain, which exhibits an extensive hydrophobic patch concealed by its flexible C-terminal helix. 25471383 4 13 theme structural 799:808 arg1 information 810:820 no structural information 796:820 no structural information 796:820 Despite its functional importance, no structural information is available for this key enzyme to date. 25471383 3 14 theme ER 559:560 arg1 control 570:576 ER quality control 559:576 ER quality control 559:576 The ER folding-sensor enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) operates as the gatekeeper for ER quality control by specifically transferring monoglucose residues to incompletely folded glycoproteins, thereby allowing them to interact with lectin chaperone complexes to facilitate their folding. 25471383 7 15 theme flexible 1314:1321 arg1 helix 1334:1338 its flexible C-terminal helix 1310:1338 its flexible C-terminal helix 1310:1338 Furthermore, we determined the three-dimensional structure of the third Trx-like domain, which exhibits an extensive hydrophobic patch concealed by its flexible C-terminal helix. 25471383 3 16 theme folding-sensor 454:467 arg1 UDP-glucose 476:486 The ER folding-sensor enzyme UDP-glucose 447:486 The ER folding-sensor enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) operates as the gatekeeper for ER quality control by specifically transferring monoglucose residues to incompletely folded glycoproteins, thereby allowing them to interact with lectin chaperone complexes to facilitate their folding. 447:759 The ER folding-sensor enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) operates as the gatekeeper for ER quality control by specifically transferring monoglucose residues to incompletely folded glycoproteins, thereby allowing them to interact with lectin chaperone complexes to facilitate their folding. 25471383 7 17 theme third 1228:1232 arg1 domain 1243:1248 the third Trx-like domain 1224:1248 the third Trx-like domain 1224:1248 Furthermore, we determined the three-dimensional structure of the third Trx-like domain, which exhibits an extensive hydrophobic patch concealed by its flexible C-terminal helix. 25471383 3 18 theme quality 562:568 arg1 control 570:576 ER quality control 559:576 ER quality control 559:576 The ER folding-sensor enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) operates as the gatekeeper for ER quality control by specifically transferring monoglucose residues to incompletely folded glycoproteins, thereby allowing them to interact with lectin chaperone complexes to facilitate their folding. 25471383 1 19 theme endoplasmic 202:212 arg1 reticulum 214:222 The endoplasmic reticulum 198:222 The endoplasmic reticulum (ER) 198:227 The endoplasmic reticulum (ER) possesses a protein quality control system that supports the efficient folding of newly synthesized glycoproteins. 25471383 1 19 theme endoplasmic 202:212 arg1 ER 225:226 ER 225:226 ER 225:226 The endoplasmic reticulum (ER) possesses a protein quality control system that supports the efficient folding of newly synthesized glycoproteins. 25471383 8 20 theme structural 1345:1354 arg1 data 1356:1359 Our structural data 1341:1359 Our structural data 1341:1359 Our structural data suggest that this hydrophobic patch is involved in intermolecular interactions, thereby contributing to the folding-sensor mechanism of UGGT. 25471383 3 21 theme monoglucose 607:617 arg1 residues 619:626 monoglucose residues 607:626 monoglucose residues 607:626 The ER folding-sensor enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) operates as the gatekeeper for ER quality control by specifically transferring monoglucose residues to incompletely folded glycoproteins, thereby allowing them to interact with lectin chaperone complexes to facilitate their folding. 25471383 0 22 theme Structural 0:9 arg1 insight 11:17 Structural insight 0:17 Structural insight into substrate recognition by the endoplasmic reticulum folding-sensor enzyme: crystal structure of third thioredoxin-like domain of UDP-glucose:glycoprotein glucosyltransferase. 0:196 Structural insight into substrate recognition by the endoplasmic reticulum folding-sensor enzyme: crystal structure of third thioredoxin-like domain of UDP-glucose:glycoprotein glucosyltransferase. 25471383 3 23 theme ER 451:452 arg1 UDP-glucose 476:486 The ER folding-sensor enzyme UDP-glucose 447:486 The ER folding-sensor enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) operates as the gatekeeper for ER quality control by specifically transferring monoglucose residues to incompletely folded glycoproteins, thereby allowing them to interact with lectin chaperone complexes to facilitate their folding. 447:759 The ER folding-sensor enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) operates as the gatekeeper for ER quality control by specifically transferring monoglucose residues to incompletely folded glycoproteins, thereby allowing them to interact with lectin chaperone complexes to facilitate their folding. 25471383 0 24 theme substrate 24:32 arg1 recognition 34:44 substrate recognition 24:44 substrate recognition 24:44 Structural insight into substrate recognition by the endoplasmic reticulum folding-sensor enzyme: crystal structure of third thioredoxin-like domain of UDP-glucose:glycoprotein glucosyltransferase. 25471383 6 25 theme UGGT 1021:1024 arg1 region 1011:1016 the folding-sensor region 992:1016 the folding-sensor region of UGGT 992:1024 Based on bioinformatics analyses, the folding-sensor region of UGGT was predicted to harbour three tandem thioredoxin (Trx)-like domains, which are often found in proteins involved in ER quality control. 25471383 0 26 theme domain 142:147 arg1 structure 106:114 crystal structure 98:114 Structural insight into substrate recognition by the endoplasmic reticulum folding-sensor enzyme: crystal structure of third thioredoxin-like domain of UDP-glucose:glycoprotein glucosyltransferase. 0:196 Structural insight into substrate recognition by the endoplasmic reticulum folding-sensor enzyme: crystal structure of third thioredoxin-like domain of UDP-glucose:glycoprotein glucosyltransferase. 25471383 6 27 theme -like 1081:1085 arg1 domains 1087:1093 three tandem thioredoxin (Trx)-like domains 1051:1093 three tandem thioredoxin (Trx)-like domains 1051:1093 Based on bioinformatics analyses, the folding-sensor region of UGGT was predicted to harbour three tandem thioredoxin (Trx)-like domains, which are often found in proteins involved in ER quality control. 25471383 3 28 gly glycoproteins 651:663 arg1 glycoproteins 651:663 incompletely folded glycoproteins 631:663 incompletely folded glycoproteins 631:663 The ER folding-sensor enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) operates as the gatekeeper for ER quality control by specifically transferring monoglucose residues to incompletely folded glycoproteins, thereby allowing them to interact with lectin chaperone complexes to facilitate their folding. 25471383 3 29 theme glycoprotein 488:499 arg1 UGGT 522:525 UGGT 522:525 UGGT 522:525 The ER folding-sensor enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) operates as the gatekeeper for ER quality control by specifically transferring monoglucose residues to incompletely folded glycoproteins, thereby allowing them to interact with lectin chaperone complexes to facilitate their folding. 25471383 3 29 theme glycoprotein 488:499 arg1 glucosyltransferase 501:519 glycoprotein glucosyltransferase 488:519 glycoprotein glucosyltransferase (UGGT) 488:526 The ER folding-sensor enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) operates as the gatekeeper for ER quality control by specifically transferring monoglucose residues to incompletely folded glycoproteins, thereby allowing them to interact with lectin chaperone complexes to facilitate their folding. 25471383 0 30 theme thioredoxin-like 125:140 arg1 UDP-glucose 152:162 UDP-glucose 152:162 UDP-glucose 152:162 Structural insight into substrate recognition by the endoplasmic reticulum folding-sensor enzyme: crystal structure of third thioredoxin-like domain of UDP-glucose:glycoprotein glucosyltransferase. 25471383 0 30 theme thioredoxin-like 125:140 arg1 domain 142:147 third thioredoxin-like domain 119:147 third thioredoxin-like domain of UDP-glucose 119:162 Structural insight into substrate recognition by the endoplasmic reticulum folding-sensor enzyme: crystal structure of third thioredoxin-like domain of UDP-glucose:glycoprotein glucosyltransferase. 25471383 7 31 theme hydrophobic 1279:1289 arg1 patch 1291:1295 an extensive hydrophobic patch 1266:1295 an extensive hydrophobic patch concealed by its flexible C-terminal helix 1266:1338 Furthermore, we determined the three-dimensional structure of the third Trx-like domain, which exhibits an extensive hydrophobic patch concealed by its flexible C-terminal helix. 25471383 8 32 theme intermolecular 1412:1425 arg1 interactions 1427:1438 intermolecular interactions 1412:1438 intermolecular interactions 1412:1438 Our structural data suggest that this hydrophobic patch is involved in intermolecular interactions, thereby contributing to the folding-sensor mechanism of UGGT. 25471383 5 33 theme structural 932:941 arg1 study 943:947 a structural study 930:947 a structural study of UGGT 930:955 To elucidate the folding-sensor mechanism in the ER, we performed a structural study of UGGT. 25471383 1 34 theme synthesized 317:327 arg1 glycoproteins 329:341 newly synthesized glycoproteins 311:341 newly synthesized glycoproteins 311:341 The endoplasmic reticulum (ER) possesses a protein quality control system that supports the efficient folding of newly synthesized glycoproteins. 25471383 0 35 theme UDP-glucose 152:162 arg1 UDP-glucose 152:162 UDP-glucose 152:162 UDP-glucose 152:162 Structural insight into substrate recognition by the endoplasmic reticulum folding-sensor enzyme: crystal structure of third thioredoxin-like domain of UDP-glucose:glycoprotein glucosyltransferase. 25471383 0 35 theme UDP-glucose 152:162 arg1 domain 142:147 third thioredoxin-like domain 119:147 third thioredoxin-like domain of UDP-glucose 119:162 Structural insight into substrate recognition by the endoplasmic reticulum folding-sensor enzyme: crystal structure of third thioredoxin-like domain of UDP-glucose:glycoprotein glucosyltransferase. 25471383 3 36 theme lectin 705:710 arg1 complexes 722:730 lectin chaperone complexes 705:730 lectin chaperone complexes 705:730 The ER folding-sensor enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) operates as the gatekeeper for ER quality control by specifically transferring monoglucose residues to incompletely folded glycoproteins, thereby allowing them to interact with lectin chaperone complexes to facilitate their folding. 25471383 3 37 theme folded 644:649 arg1 glycoproteins 651:663 incompletely folded glycoproteins 631:663 incompletely folded glycoproteins 631:663 The ER folding-sensor enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) operates as the gatekeeper for ER quality control by specifically transferring monoglucose residues to incompletely folded glycoproteins, thereby allowing them to interact with lectin chaperone complexes to facilitate their folding. 25471383 2 38 theme quality 433:439 arg1 series 362:367 a series 360:367 a series of N-linked glycan intermediates displayed on proteins 360:422 In this system, a series of N-linked glycan intermediates displayed on proteins serve as quality tags. 25471383 2 38 theme quality 433:439 arg1 tags 441:444 quality tags 433:444 quality tags 433:444 In this system, a series of N-linked glycan intermediates displayed on proteins serve as quality tags. 25471383 1 39 theme glycoproteins 329:341 arg1 folding 300:306 the efficient folding 286:306 the efficient folding of newly synthesized glycoproteins 286:341 The endoplasmic reticulum (ER) possesses a protein quality control system that supports the efficient folding of newly synthesized glycoproteins. 25471383 3 40 gly glycoprotein 488:499 arg1 glycoprotein 488:499 glycoprotein glucosyltransferase 488:519 glycoprotein glucosyltransferase (UGGT) 488:526 The ER folding-sensor enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) operates as the gatekeeper for ER quality control by specifically transferring monoglucose residues to incompletely folded glycoproteins, thereby allowing them to interact with lectin chaperone complexes to facilitate their folding. 25471383 0 41 theme endoplasmic 53:63 arg1 reticulum 65:73 the endoplasmic reticulum 49:73 the endoplasmic reticulum folding-sensor enzyme 49:95 Structural insight into substrate recognition by the endoplasmic reticulum folding-sensor enzyme: crystal structure of third thioredoxin-like domain of UDP-glucose:glycoprotein glucosyltransferase. 25471383 6 42 theme folding-sensor 996:1009 arg1 region 1011:1016 the folding-sensor region 992:1016 the folding-sensor region of UGGT 992:1024 Based on bioinformatics analyses, the folding-sensor region of UGGT was predicted to harbour three tandem thioredoxin (Trx)-like domains, which are often found in proteins involved in ER quality control. 25471383 0 43 theme glycoprotein 164:175 arg1 glucosyltransferase 177:195 glycoprotein glucosyltransferase 164:195 Structural insight into substrate recognition by the endoplasmic reticulum folding-sensor enzyme: crystal structure of third thioredoxin-like domain of UDP-glucose:glycoprotein glucosyltransferase. 0:196 Structural insight into substrate recognition by the endoplasmic reticulum folding-sensor enzyme: crystal structure of third thioredoxin-like domain of UDP-glucose:glycoprotein glucosyltransferase. 25471383 7 44 theme domain 1243:1248 arg1 structure 1211:1219 the three-dimensional structure 1189:1219 the three-dimensional structure of the third Trx-like domain, which exhibits an extensive hydrophobic patch concealed by its flexible C-terminal helix 1189:1338 Furthermore, we determined the three-dimensional structure of the third Trx-like domain, which exhibits an extensive hydrophobic patch concealed by its flexible C-terminal helix. 25471383 4 45 theme functional 773:782 arg1 importance 784:793 its functional importance 769:793 its functional importance 769:793 Despite its functional importance, no structural information is available for this key enzyme to date. 25471383 5 46 from mechanism 896:904 arg1 ER 913:914 the ER 909:914 the ER 909:914 To elucidate the folding-sensor mechanism in the ER, we performed a structural study of UGGT. 25471383 7 47 theme C-terminal 1323:1332 arg1 helix 1334:1338 its flexible C-terminal helix 1310:1338 its flexible C-terminal helix 1310:1338 Furthermore, we determined the three-dimensional structure of the third Trx-like domain, which exhibits an extensive hydrophobic patch concealed by its flexible C-terminal helix. 25471383 1 48 contain possesses 229:237 arg1 reticulum 214:222 The endoplasmic reticulum 198:222 The endoplasmic reticulum (ER) 198:227 The endoplasmic reticulum (ER) possesses a protein quality control system that supports the efficient folding of newly synthesized glycoproteins. 25471383 1 48 contain possesses 229:237 arg2 system 265:270 a protein quality control system 239:270 a protein quality control system that supports the efficient folding of newly synthesized glycoproteins 239:341 The endoplasmic reticulum (ER) possesses a protein quality control system that supports the efficient folding of newly synthesized glycoproteins. 25471383 1 48 contain possesses 229:237 arg1 ER 225:226 ER 225:226 ER 225:226 The endoplasmic reticulum (ER) possesses a protein quality control system that supports the efficient folding of newly synthesized glycoproteins. 25471383 3 49 dep UDP-glucose 476:486 arg1 operates 528:535 operates 528:535 operates 528:535 The ER folding-sensor enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) operates as the gatekeeper for ER quality control by specifically transferring monoglucose residues to incompletely folded glycoproteins, thereby allowing them to interact with lectin chaperone complexes to facilitate their folding. 25471383 6 50 theme quality 1145:1151 arg1 control 1153:1159 ER quality control 1142:1159 ER quality control 1142:1159 Based on bioinformatics analyses, the folding-sensor region of UGGT was predicted to harbour three tandem thioredoxin (Trx)-like domains, which are often found in proteins involved in ER quality control. 25471383 6 51 theme ER 1142:1143 arg1 control 1153:1159 ER quality control 1142:1159 ER quality control 1142:1159 Based on bioinformatics analyses, the folding-sensor region of UGGT was predicted to harbour three tandem thioredoxin (Trx)-like domains, which are often found in proteins involved in ER quality control. 25471383 1 52 theme protein 241:247 arg1 system 265:270 a protein quality control system 239:270 a protein quality control system that supports the efficient folding of newly synthesized glycoproteins 239:341 The endoplasmic reticulum (ER) possesses a protein quality control system that supports the efficient folding of newly synthesized glycoproteins. 25471383 4 53 theme key 844:846 arg1 enzyme 848:853 this key enzyme 839:853 this key enzyme to date 839:861 Despite its functional importance, no structural information is available for this key enzyme to date. 25471383 3 54 theme chaperone 712:720 arg1 complexes 722:730 lectin chaperone complexes 705:730 lectin chaperone complexes 705:730 The ER folding-sensor enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) operates as the gatekeeper for ER quality control by specifically transferring monoglucose residues to incompletely folded glycoproteins, thereby allowing them to interact with lectin chaperone complexes to facilitate their folding. 25471383 8 55 theme folding-sensor 1469:1482 arg1 mechanism 1484:1492 the folding-sensor mechanism 1465:1492 the folding-sensor mechanism of UGGT 1465:1500 Our structural data suggest that this hydrophobic patch is involved in intermolecular interactions, thereby contributing to the folding-sensor mechanism of UGGT. 25471383 2 56 theme glycan 381:386 arg1 intermediates 388:400 N-linked glycan intermediates 372:400 N-linked glycan intermediates displayed on proteins 372:422 In this system, a series of N-linked glycan intermediates displayed on proteins serve as quality tags. 25471383 1 57 theme quality 249:255 arg1 system 265:270 a protein quality control system 239:270 a protein quality control system that supports the efficient folding of newly synthesized glycoproteins 239:341 The endoplasmic reticulum (ER) possesses a protein quality control system that supports the efficient folding of newly synthesized glycoproteins. 25471383 0 58 theme folding-sensor 75:88 arg1 enzyme 90:95 the endoplasmic reticulum folding-sensor enzyme 49:95 the endoplasmic reticulum folding-sensor enzyme 49:95 Structural insight into substrate recognition by the endoplasmic reticulum folding-sensor enzyme: crystal structure of third thioredoxin-like domain of UDP-glucose:glycoprotein glucosyltransferase. 25471383 0 59 dep insight 11:17 arg1 structure 106:114 crystal structure 98:114 Structural insight into substrate recognition by the endoplasmic reticulum folding-sensor enzyme: crystal structure of third thioredoxin-like domain of UDP-glucose:glycoprotein glucosyltransferase. 0:196 Structural insight into substrate recognition by the endoplasmic reticulum folding-sensor enzyme: crystal structure of third thioredoxin-like domain of UDP-glucose:glycoprotein glucosyltransferase. 25471383 0 59 dep insight 11:17 arg1 glucosyltransferase 177:195 glycoprotein glucosyltransferase 164:195 Structural insight into substrate recognition by the endoplasmic reticulum folding-sensor enzyme: crystal structure of third thioredoxin-like domain of UDP-glucose:glycoprotein glucosyltransferase. 0:196 Structural insight into substrate recognition by the endoplasmic reticulum folding-sensor enzyme: crystal structure of third thioredoxin-like domain of UDP-glucose:glycoprotein glucosyltransferase. 25471383 1 60 gly glycoproteins 329:341 arg1 glycoproteins 329:341 newly synthesized glycoproteins 311:341 newly synthesized glycoproteins 311:341 The endoplasmic reticulum (ER) possesses a protein quality control system that supports the efficient folding of newly synthesized glycoproteins. 25471383 2 61 theme intermediates 388:400 arg1 series 362:367 a series 360:367 a series of N-linked glycan intermediates displayed on proteins 360:422 In this system, a series of N-linked glycan intermediates displayed on proteins serve as quality tags. 25471383 2 61 theme intermediates 388:400 arg1 tags 441:444 quality tags 433:444 quality tags 433:444 In this system, a series of N-linked glycan intermediates displayed on proteins serve as quality tags. 25471383 3 62 theme enzyme 469:474 arg1 UDP-glucose 476:486 The ER folding-sensor enzyme UDP-glucose 447:486 The ER folding-sensor enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) operates as the gatekeeper for ER quality control by specifically transferring monoglucose residues to incompletely folded glycoproteins, thereby allowing them to interact with lectin chaperone complexes to facilitate their folding. 447:759 The ER folding-sensor enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) operates as the gatekeeper for ER quality control by specifically transferring monoglucose residues to incompletely folded glycoproteins, thereby allowing them to interact with lectin chaperone complexes to facilitate their folding. 25471383 1 63 theme control 257:263 arg1 system 265:270 a protein quality control system 239:270 a protein quality control system that supports the efficient folding of newly synthesized glycoproteins 239:341 The endoplasmic reticulum (ER) possesses a protein quality control system that supports the efficient folding of newly synthesized glycoproteins. 25471383 0 64 theme reticulum 65:73 arg1 enzyme 90:95 the endoplasmic reticulum folding-sensor enzyme 49:95 the endoplasmic reticulum folding-sensor enzyme 49:95 Structural insight into substrate recognition by the endoplasmic reticulum folding-sensor enzyme: crystal structure of third thioredoxin-like domain of UDP-glucose:glycoprotein glucosyltransferase. 25471383 6 65 theme bioinformatics 967:980 arg1 analyses 982:989 bioinformatics analyses 967:989 bioinformatics analyses 967:989 Based on bioinformatics analyses, the folding-sensor region of UGGT was predicted to harbour three tandem thioredoxin (Trx)-like domains, which are often found in proteins involved in ER quality control. 25471383 5 66 theme folding-sensor 881:894 arg1 mechanism 896:904 the folding-sensor mechanism 877:904 the folding-sensor mechanism in the ER 877:914 To elucidate the folding-sensor mechanism in the ER, we performed a structural study of UGGT. 25471383 0 67 gly glycoprotein 164:175 arg1 glycoprotein 164:175 glycoprotein glucosyltransferase 164:195 Structural insight into substrate recognition by the endoplasmic reticulum folding-sensor enzyme: crystal structure of third thioredoxin-like domain of UDP-glucose:glycoprotein glucosyltransferase. 0:196 Structural insight into substrate recognition by the endoplasmic reticulum folding-sensor enzyme: crystal structure of third thioredoxin-like domain of UDP-glucose:glycoprotein glucosyltransferase. 25471383 6 68 theme tandem 1057:1062 arg1 domains 1087:1093 three tandem thioredoxin (Trx)-like domains 1051:1093 three tandem thioredoxin (Trx)-like domains 1051:1093 Based on bioinformatics analyses, the folding-sensor region of UGGT was predicted to harbour three tandem thioredoxin (Trx)-like domains, which are often found in proteins involved in ER quality control. 25411339 7 0 theme COP-I 1323:1327 arg1 machinery 1337:1345 COP-I vesicle machinery 1323:1345 COP-I vesicle machinery 1323:1345 The QCVs are highly mobile, displaying dynamics that are dependent on microtubules and COP-II but not on COP-I vesicle machinery. 25411339 4 1 link ER-derived 717:726 arg1 membrane 703:710 the ER membrane 696:710 the ER membrane 696:710 One such question is the subcellular localization of ERManI, which has been suggested to localize to the ER membrane, the ER-derived quality control compartment (ERQC), and, surprisingly, recently to the Golgi apparatus. 25411339 4 1 link ER-derived 717:726 arg1 ERQC 757:760 ERQC 757:760 ERQC 757:760 One such question is the subcellular localization of ERManI, which has been suggested to localize to the ER membrane, the ER-derived quality control compartment (ERQC), and, surprisingly, recently to the Golgi apparatus. 25411339 4 1 link ER-derived 717:726 arg1 compartment 744:754 the ER-derived quality control compartment 713:754 the ER-derived quality control compartment (ERQC) 713:761 One such question is the subcellular localization of ERManI, which has been suggested to localize to the ER membrane, the ER-derived quality control compartment (ERQC), and, surprisingly, recently to the Golgi apparatus. 25411339 1 2 with glycoproteins 303:315 arg1 time 322:325 time 322:325 time 322:325 Endoplasmic reticulum α1,2 mannosidase I (ERManI), a central component of ER quality control and ER-associated degradation (ERAD), acts as a timer enzyme, modifying N-linked sugar chains of glycoproteins with time. 25411339 8 3 theme juxtanuclear 1399:1410 arg1 region 1412:1417 a juxtanuclear region 1397:1417 a juxtanuclear region 1397:1417 Under ER stress conditions, the QCVs converge in a juxtanuclear region, at the ERQC, as previously reported. 25411339 9 4 theme active 1515:1520 arg1 process 1533:1539 an active autophagic process 1512:1539 an active autophagic process 1512:1539 Our results also suggest that ERManI is turned over by an active autophagic process. 25411339 7 5 theme vesicle 1329:1335 arg1 machinery 1337:1345 COP-I vesicle machinery 1323:1345 COP-I vesicle machinery 1323:1345 The QCVs are highly mobile, displaying dynamics that are dependent on microtubules and COP-II but not on COP-I vesicle machinery. 25411339 10 6 from ERManI 1674:1679 arg1 pattern 1692:1698 a Golgi pattern 1684:1698 a Golgi pattern 1684:1698 Of importance, we found that membrane disturbance, as is common in immunofluorescence methods, leads to an artificial appearance of ERManI in a Golgi pattern. 25411339 1 7 theme glycoproteins 303:315 arg1 chains 293:298 N-linked sugar chains 278:298 N-linked sugar chains of glycoproteins with time 278:325 Endoplasmic reticulum α1,2 mannosidase I (ERManI), a central component of ER quality control and ER-associated degradation (ERAD), acts as a timer enzyme, modifying N-linked sugar chains of glycoproteins with time. 25411339 9 8 theme autophagic 1522:1531 arg1 process 1533:1539 an active autophagic process 1512:1539 an active autophagic process 1512:1539 Our results also suggest that ERManI is turned over by an active autophagic process. 25411339 5 9 dep try 819:821 arg1 clarify 826:832 clarify 826:832 To try to clarify this controversy 816:849 To try to clarify this controversy, we applied a series of approaches that indicate that ERManI is located, at the steady state, in quality control vesicles (QCVs) to which ERAD substrates are transported and in which they interact with the enzyme. 25411339 3 10 gly glycoprotein 499:510 arg1 glycoprotein 499:510 glycoprotein quality control 499:526 glycoprotein quality control 499:526 Despite the importance of ERManI in maintenance of glycoprotein quality control, fundamental questions regarding this enzyme remain controversial. 25411339 4 11 theme quality 728:734 arg1 membrane 703:710 the ER membrane 696:710 the ER membrane 696:710 One such question is the subcellular localization of ERManI, which has been suggested to localize to the ER membrane, the ER-derived quality control compartment (ERQC), and, surprisingly, recently to the Golgi apparatus. 25411339 4 11 theme quality 728:734 arg1 ERQC 757:760 ERQC 757:760 ERQC 757:760 One such question is the subcellular localization of ERManI, which has been suggested to localize to the ER membrane, the ER-derived quality control compartment (ERQC), and, surprisingly, recently to the Golgi apparatus. 25411339 4 11 theme quality 728:734 arg1 compartment 744:754 the ER-derived quality control compartment 713:754 the ER-derived quality control compartment (ERQC) 713:761 One such question is the subcellular localization of ERManI, which has been suggested to localize to the ER membrane, the ER-derived quality control compartment (ERQC), and, surprisingly, recently to the Golgi apparatus. 25411339 6 12 theme endogenous 1070:1079 arg1 ERManI 1107:1112 Both endogenous and exogenously expressed ERManI 1065:1112 Both endogenous and exogenously expressed ERManI 1065:1112 Both endogenous and exogenously expressed ERManI migrate at an ER-like density on iodixanol gradients, suggesting that the QCVs are derived from the ER. 25411339 6 13 theme expressed 1097:1105 arg1 ERManI 1107:1112 Both endogenous and exogenously expressed ERManI 1065:1112 Both endogenous and exogenously expressed ERManI 1065:1112 Both endogenous and exogenously expressed ERManI migrate at an ER-like density on iodixanol gradients, suggesting that the QCVs are derived from the ER. 25411339 3 14 theme fundamental 529:539 arg1 questions 541:549 fundamental questions 529:549 fundamental questions regarding this enzyme 529:571 Despite the importance of ERManI in maintenance of glycoprotein quality control, fundamental questions regarding this enzyme remain controversial. 25411339 5 15 from state 938:942 arg1 located 915:921 located 915:921 located 915:921 To try to clarify this controversy, we applied a series of approaches that indicate that ERManI is located, at the steady state, in quality control vesicles (QCVs) to which ERAD substrates are transported and in which they interact with the enzyme. 25411339 5 16 theme approaches 875:884 arg1 series 865:870 a series 863:870 a series of approaches that indicate that ERManI is located, at the steady state, in quality control vesicles (QCVs) to which ERAD substrates are transported and in which they interact with the enzyme 863:1062 To try to clarify this controversy, we applied a series of approaches that indicate that ERManI is located, at the steady state, in quality control vesicles (QCVs) to which ERAD substrates are transported and in which they interact with the enzyme. 25411339 10 17 theme membrane 1571:1578 arg1 disturbance 1580:1590 membrane disturbance 1571:1590 membrane disturbance 1571:1590 Of importance, we found that membrane disturbance, as is common in immunofluorescence methods, leads to an artificial appearance of ERManI in a Golgi pattern. 25411339 2 18 gly glycoprotein 347:358 arg1 glycoprotein 347:358 glycoprotein folding attempts 347:375 glycoprotein folding attempts 347:375 This process halts glycoprotein folding attempts when necessary and targets terminally misfolded glycoproteins to ERAD. 25411339 10 19 from common 1599:1604 arg1 methods 1628:1634 immunofluorescence methods 1609:1634 immunofluorescence methods 1609:1634 Of importance, we found that membrane disturbance, as is common in immunofluorescence methods, leads to an artificial appearance of ERManI in a Golgi pattern. 25411339 3 20 theme quality 512:518 arg1 control 520:526 glycoprotein quality control 499:526 glycoprotein quality control 499:526 Despite the importance of ERManI in maintenance of glycoprotein quality control, fundamental questions regarding this enzyme remain controversial. 25411339 0 21 theme glycoprotein 88:99 arg1 substrates 101:110 its glycoprotein substrates 84:110 its glycoprotein substrates 84:110 Mammalian ER mannosidase I resides in quality control vesicles, where it encounters its glycoprotein substrates. 25411339 10 22 dep leads 1637:1641 arg1 common 1599:1604 common 1599:1604 common 1599:1604 Of importance, we found that membrane disturbance, as is common in immunofluorescence methods, leads to an artificial appearance of ERManI in a Golgi pattern. 25411339 4 23 theme Golgi 799:803 arg1 apparatus 805:813 the Golgi apparatus 795:813 the Golgi apparatus 795:813 One such question is the subcellular localization of ERManI, which has been suggested to localize to the ER membrane, the ER-derived quality control compartment (ERQC), and, surprisingly, recently to the Golgi apparatus. 25411339 2 24 theme misfolded 415:423 arg1 glycoproteins 425:437 terminally misfolded glycoproteins 404:437 terminally misfolded glycoproteins 404:437 This process halts glycoprotein folding attempts when necessary and targets terminally misfolded glycoproteins to ERAD. 25411339 1 25 gly glycoproteins 303:315 arg1 glycoproteins 303:315 glycoproteins 303:315 glycoproteins with time 303:325 Endoplasmic reticulum α1,2 mannosidase I (ERManI), a central component of ER quality control and ER-associated degradation (ERAD), acts as a timer enzyme, modifying N-linked sugar chains of glycoproteins with time. 25411339 2 26 theme glycoprotein 347:358 arg1 folding 360:366 glycoprotein folding attempts 347:375 glycoprotein folding attempts 347:375 This process halts glycoprotein folding attempts when necessary and targets terminally misfolded glycoproteins to ERAD. 25411339 0 27 theme ER 10:11 arg1 mannosidase 13:23 Mammalian ER mannosidase I 0:25 Mammalian ER mannosidase I 0:25 Mammalian ER mannosidase I resides in quality control vesicles, where it encounters its glycoprotein substrates. 25411339 3 28 from importance 460:469 arg1 maintenance 484:494 maintenance 484:494 maintenance of glycoprotein quality control 484:526 Despite the importance of ERManI in maintenance of glycoprotein quality control, fundamental questions regarding this enzyme remain controversial. 25411339 4 29 theme ER-derived 717:726 arg1 membrane 703:710 the ER membrane 696:710 the ER membrane 696:710 One such question is the subcellular localization of ERManI, which has been suggested to localize to the ER membrane, the ER-derived quality control compartment (ERQC), and, surprisingly, recently to the Golgi apparatus. 25411339 4 29 theme ER-derived 717:726 arg1 ERQC 757:760 ERQC 757:760 ERQC 757:760 One such question is the subcellular localization of ERManI, which has been suggested to localize to the ER membrane, the ER-derived quality control compartment (ERQC), and, surprisingly, recently to the Golgi apparatus. 25411339 4 29 theme ER-derived 717:726 arg1 compartment 744:754 the ER-derived quality control compartment 713:754 the ER-derived quality control compartment (ERQC) 713:761 One such question is the subcellular localization of ERManI, which has been suggested to localize to the ER membrane, the ER-derived quality control compartment (ERQC), and, surprisingly, recently to the Golgi apparatus. 25411339 0 30 theme Mammalian 0:8 arg1 mannosidase 13:23 Mammalian ER mannosidase I 0:25 Mammalian ER mannosidase I 0:25 Mammalian ER mannosidase I resides in quality control vesicles, where it encounters its glycoprotein substrates. 25411339 5 31 located located 915:921 arg1 state 938:942 the steady state 927:942 the steady state 927:942 To try to clarify this controversy, we applied a series of approaches that indicate that ERManI is located, at the steady state, in quality control vesicles (QCVs) to which ERAD substrates are transported and in which they interact with the enzyme. 25411339 5 31 located located 915:921 arg2 ERManI 905:910 ERManI 905:910 ERManI 905:910 To try to clarify this controversy, we applied a series of approaches that indicate that ERManI is located, at the steady state, in quality control vesicles (QCVs) to which ERAD substrates are transported and in which they interact with the enzyme. 25411339 5 31 located located 915:921 arg1 QCVs 974:977 QCVs 974:977 QCVs 974:977 To try to clarify this controversy, we applied a series of approaches that indicate that ERManI is located, at the steady state, in quality control vesicles (QCVs) to which ERAD substrates are transported and in which they interact with the enzyme. 25411339 5 31 located located 915:921 arg1 vesicles 964:971 quality control vesicles 948:971 quality control vesicles (QCVs) to which ERAD substrates are transported and in which they interact with the enzyme 948:1062 To try to clarify this controversy, we applied a series of approaches that indicate that ERManI is located, at the steady state, in quality control vesicles (QCVs) to which ERAD substrates are transported and in which they interact with the enzyme. 25411339 5 32 theme steady 931:936 arg1 state 938:942 the steady state 927:942 the steady state 927:942 To try to clarify this controversy, we applied a series of approaches that indicate that ERManI is located, at the steady state, in quality control vesicles (QCVs) to which ERAD substrates are transported and in which they interact with the enzyme. 25411339 6 33 attach derived 1197:1203 arg2 QCVs 1188:1191 the QCVs 1184:1191 the QCVs 1184:1191 Both endogenous and exogenously expressed ERManI migrate at an ER-like density on iodixanol gradients, suggesting that the QCVs are derived from the ER. 25411339 6 33 attach derived 1197:1203 arg1 ER 1214:1215 the ER 1210:1215 the ER 1210:1215 Both endogenous and exogenously expressed ERManI migrate at an ER-like density on iodixanol gradients, suggesting that the QCVs are derived from the ER. 25411339 1 34 theme central 166:172 arg1 I 152:152 Endoplasmic reticulum α1,2 mannosidase I 113:152 Endoplasmic reticulum α1,2 mannosidase I (ERManI) 113:161 Endoplasmic reticulum α1,2 mannosidase I (ERManI), a central component of ER quality control and ER-associated degradation (ERAD), acts as a timer enzyme, modifying N-linked sugar chains of glycoproteins with time. 25411339 1 34 theme central 166:172 arg1 component 174:182 a central component 164:182 a central component of ER quality control and ER-associated degradation (ERAD) 164:241 Endoplasmic reticulum α1,2 mannosidase I (ERManI), a central component of ER quality control and ER-associated degradation (ERAD), acts as a timer enzyme, modifying N-linked sugar chains of glycoproteins with time. 25411339 0 35 gly glycoprotein 88:99 arg1 glycoprotein 88:99 its glycoprotein substrates 84:110 its glycoprotein substrates 84:110 Mammalian ER mannosidase I resides in quality control vesicles, where it encounters its glycoprotein substrates. 25411339 5 36 from vesicles 964:971 arg1 located 915:921 located 915:921 located 915:921 To try to clarify this controversy, we applied a series of approaches that indicate that ERManI is located, at the steady state, in quality control vesicles (QCVs) to which ERAD substrates are transported and in which they interact with the enzyme. 25411339 3 37 theme ERManI 474:479 arg1 importance 460:469 the importance 456:469 the importance of ERManI in maintenance of glycoprotein quality control 456:526 Despite the importance of ERManI in maintenance of glycoprotein quality control, fundamental questions regarding this enzyme remain controversial. 25411339 10 38 theme immunofluorescence 1609:1626 arg1 methods 1628:1634 immunofluorescence methods 1609:1634 immunofluorescence methods 1609:1634 Of importance, we found that membrane disturbance, as is common in immunofluorescence methods, leads to an artificial appearance of ERManI in a Golgi pattern. 25411339 4 39 theme subcellular 620:630 arg1 question 604:611 One such question 595:611 One such question 595:611 One such question is the subcellular localization of ERManI, which has been suggested to localize to the ER membrane, the ER-derived quality control compartment (ERQC), and, surprisingly, recently to the Golgi apparatus. 25411339 4 39 theme subcellular 620:630 arg1 localization 632:643 the subcellular localization 616:643 the subcellular localization of ERManI, which has been suggested to localize to the ER membrane, the ER-derived quality control compartment (ERQC), and, surprisingly, recently to the Golgi apparatus 616:813 One such question is the subcellular localization of ERManI, which has been suggested to localize to the ER membrane, the ER-derived quality control compartment (ERQC), and, surprisingly, recently to the Golgi apparatus. 25411339 1 40 theme timer 254:258 arg1 I 152:152 Endoplasmic reticulum α1,2 mannosidase I 113:152 Endoplasmic reticulum α1,2 mannosidase I (ERManI) 113:161 Endoplasmic reticulum α1,2 mannosidase I (ERManI), a central component of ER quality control and ER-associated degradation (ERAD), acts as a timer enzyme, modifying N-linked sugar chains of glycoproteins with time. 25411339 1 40 theme timer 254:258 arg1 enzyme 260:265 a timer enzyme 252:265 a timer enzyme 252:265 Endoplasmic reticulum α1,2 mannosidase I (ERManI), a central component of ER quality control and ER-associated degradation (ERAD), acts as a timer enzyme, modifying N-linked sugar chains of glycoproteins with time. 25411339 4 41 theme ERManI 648:653 arg1 question 604:611 One such question 595:611 One such question 595:611 One such question is the subcellular localization of ERManI, which has been suggested to localize to the ER membrane, the ER-derived quality control compartment (ERQC), and, surprisingly, recently to the Golgi apparatus. 25411339 4 41 theme ERManI 648:653 arg1 localization 632:643 the subcellular localization 616:643 the subcellular localization of ERManI, which has been suggested to localize to the ER membrane, the ER-derived quality control compartment (ERQC), and, surprisingly, recently to the Golgi apparatus 616:813 One such question is the subcellular localization of ERManI, which has been suggested to localize to the ER membrane, the ER-derived quality control compartment (ERQC), and, surprisingly, recently to the Golgi apparatus. 25411339 10 42 theme ERManI 1674:1679 arg1 appearance 1660:1669 an artificial appearance 1646:1669 an artificial appearance of ERManI in a Golgi pattern 1646:1698 Of importance, we found that membrane disturbance, as is common in immunofluorescence methods, leads to an artificial appearance of ERManI in a Golgi pattern. 25411339 1 43 theme ER 187:188 arg1 control 198:204 ER quality control 187:204 ER quality control 187:204 Endoplasmic reticulum α1,2 mannosidase I (ERManI), a central component of ER quality control and ER-associated degradation (ERAD), acts as a timer enzyme, modifying N-linked sugar chains of glycoproteins with time. 25411339 8 44 theme stress 1357:1362 arg1 conditions 1364:1373 ER stress conditions 1354:1373 ER stress conditions 1354:1373 Under ER stress conditions, the QCVs converge in a juxtanuclear region, at the ERQC, as previously reported. 25411339 5 45 theme quality 948:954 arg1 QCVs 974:977 QCVs 974:977 QCVs 974:977 To try to clarify this controversy, we applied a series of approaches that indicate that ERManI is located, at the steady state, in quality control vesicles (QCVs) to which ERAD substrates are transported and in which they interact with the enzyme. 25411339 5 45 theme quality 948:954 arg1 vesicles 964:971 quality control vesicles 948:971 quality control vesicles (QCVs) to which ERAD substrates are transported and in which they interact with the enzyme 948:1062 To try to clarify this controversy, we applied a series of approaches that indicate that ERManI is located, at the steady state, in quality control vesicles (QCVs) to which ERAD substrates are transported and in which they interact with the enzyme. 25411339 1 46 theme quality 190:196 arg1 control 198:204 ER quality control 187:204 ER quality control 187:204 Endoplasmic reticulum α1,2 mannosidase I (ERManI), a central component of ER quality control and ER-associated degradation (ERAD), acts as a timer enzyme, modifying N-linked sugar chains of glycoproteins with time. 25411339 0 47 theme control 46:52 arg1 vesicles 54:61 quality control vesicles 38:61 quality control vesicles 38:61 Mammalian ER mannosidase I resides in quality control vesicles, where it encounters its glycoprotein substrates. 25411339 10 48 theme Golgi 1686:1690 arg1 pattern 1692:1698 a Golgi pattern 1684:1698 a Golgi pattern 1684:1698 Of importance, we found that membrane disturbance, as is common in immunofluorescence methods, leads to an artificial appearance of ERManI in a Golgi pattern. 25411339 10 49 from appearance 1660:1669 arg1 pattern 1692:1698 a Golgi pattern 1684:1698 a Golgi pattern 1684:1698 Of importance, we found that membrane disturbance, as is common in immunofluorescence methods, leads to an artificial appearance of ERManI in a Golgi pattern. 25411339 8 50 theme ER 1354:1355 arg1 conditions 1364:1373 ER stress conditions 1354:1373 ER stress conditions 1354:1373 Under ER stress conditions, the QCVs converge in a juxtanuclear region, at the ERQC, as previously reported. 25411339 5 51 theme control 956:962 arg1 QCVs 974:977 QCVs 974:977 QCVs 974:977 To try to clarify this controversy, we applied a series of approaches that indicate that ERManI is located, at the steady state, in quality control vesicles (QCVs) to which ERAD substrates are transported and in which they interact with the enzyme. 25411339 5 51 theme control 956:962 arg1 vesicles 964:971 quality control vesicles 948:971 quality control vesicles (QCVs) to which ERAD substrates are transported and in which they interact with the enzyme 948:1062 To try to clarify this controversy, we applied a series of approaches that indicate that ERManI is located, at the steady state, in quality control vesicles (QCVs) to which ERAD substrates are transported and in which they interact with the enzyme. 25411339 1 52 link N-linked 278:285 arg1 chains 293:298 N-linked sugar chains 278:298 N-linked sugar chains of glycoproteins with time 278:325 Endoplasmic reticulum α1,2 mannosidase I (ERManI), a central component of ER quality control and ER-associated degradation (ERAD), acts as a timer enzyme, modifying N-linked sugar chains of glycoproteins with time. 25411339 4 53 theme ER 700:701 arg1 membrane 703:710 the ER membrane 696:710 the ER membrane 696:710 One such question is the subcellular localization of ERManI, which has been suggested to localize to the ER membrane, the ER-derived quality control compartment (ERQC), and, surprisingly, recently to the Golgi apparatus. 25411339 4 53 theme ER 700:701 arg1 compartment 744:754 the ER-derived quality control compartment 713:754 the ER-derived quality control compartment (ERQC) 713:761 One such question is the subcellular localization of ERManI, which has been suggested to localize to the ER membrane, the ER-derived quality control compartment (ERQC), and, surprisingly, recently to the Golgi apparatus. 25411339 0 54 theme quality 38:44 arg1 vesicles 54:61 quality control vesicles 38:61 quality control vesicles 38:61 Mammalian ER mannosidase I resides in quality control vesicles, where it encounters its glycoprotein substrates. 25411339 10 55 theme artificial 1649:1658 arg1 appearance 1660:1669 an artificial appearance 1646:1669 an artificial appearance of ERManI in a Golgi pattern 1646:1698 Of importance, we found that membrane disturbance, as is common in immunofluorescence methods, leads to an artificial appearance of ERManI in a Golgi pattern. 25411339 10 56 from pattern 1692:1698 arg1 appearance 1660:1669 an artificial appearance 1646:1669 an artificial appearance of ERManI in a Golgi pattern 1646:1698 Of importance, we found that membrane disturbance, as is common in immunofluorescence methods, leads to an artificial appearance of ERManI in a Golgi pattern. 25411339 1 57 theme Endoplasmic 113:123 arg1 reticulum 125:133 Endoplasmic reticulum 113:133 Endoplasmic reticulum α1,2 mannosidase I (ERManI) 113:161 Endoplasmic reticulum α1,2 mannosidase I (ERManI), a central component of ER quality control and ER-associated degradation (ERAD), acts as a timer enzyme, modifying N-linked sugar chains of glycoproteins with time. 25411339 1 58 theme N-linked 278:285 arg1 chains 293:298 N-linked sugar chains 278:298 N-linked sugar chains of glycoproteins with time 278:325 Endoplasmic reticulum α1,2 mannosidase I (ERManI), a central component of ER quality control and ER-associated degradation (ERAD), acts as a timer enzyme, modifying N-linked sugar chains of glycoproteins with time. 25411339 6 59 theme ER-like 1128:1134 arg1 density 1136:1142 an ER-like density 1125:1142 an ER-like density on iodixanol gradients 1125:1165 Both endogenous and exogenously expressed ERManI migrate at an ER-like density on iodixanol gradients, suggesting that the QCVs are derived from the ER. 25411339 6 60 theme iodixanol 1147:1155 arg1 gradients 1157:1165 iodixanol gradients 1147:1165 iodixanol gradients 1147:1165 Both endogenous and exogenously expressed ERManI migrate at an ER-like density on iodixanol gradients, suggesting that the QCVs are derived from the ER. 25411339 1 61 theme reticulum 125:133 arg1 I 152:152 Endoplasmic reticulum α1,2 mannosidase I 113:152 Endoplasmic reticulum α1,2 mannosidase I (ERManI) 113:161 Endoplasmic reticulum α1,2 mannosidase I (ERManI), a central component of ER quality control and ER-associated degradation (ERAD), acts as a timer enzyme, modifying N-linked sugar chains of glycoproteins with time. 25411339 1 61 theme reticulum 125:133 arg1 enzyme 260:265 a timer enzyme 252:265 a timer enzyme 252:265 Endoplasmic reticulum α1,2 mannosidase I (ERManI), a central component of ER quality control and ER-associated degradation (ERAD), acts as a timer enzyme, modifying N-linked sugar chains of glycoproteins with time. 25411339 1 61 theme reticulum 125:133 arg1 component 174:182 a central component 164:182 a central component of ER quality control and ER-associated degradation (ERAD) 164:241 Endoplasmic reticulum α1,2 mannosidase I (ERManI), a central component of ER quality control and ER-associated degradation (ERAD), acts as a timer enzyme, modifying N-linked sugar chains of glycoproteins with time. 25411339 1 61 theme reticulum 125:133 arg1 ERManI 155:160 ERManI 155:160 ERManI 155:160 Endoplasmic reticulum α1,2 mannosidase I (ERManI), a central component of ER quality control and ER-associated degradation (ERAD), acts as a timer enzyme, modifying N-linked sugar chains of glycoproteins with time. 25411339 4 62 theme control 736:742 arg1 membrane 703:710 the ER membrane 696:710 the ER membrane 696:710 One such question is the subcellular localization of ERManI, which has been suggested to localize to the ER membrane, the ER-derived quality control compartment (ERQC), and, surprisingly, recently to the Golgi apparatus. 25411339 4 62 theme control 736:742 arg1 ERQC 757:760 ERQC 757:760 ERQC 757:760 One such question is the subcellular localization of ERManI, which has been suggested to localize to the ER membrane, the ER-derived quality control compartment (ERQC), and, surprisingly, recently to the Golgi apparatus. 25411339 4 62 theme control 736:742 arg1 compartment 744:754 the ER-derived quality control compartment 713:754 the ER-derived quality control compartment (ERQC) 713:761 One such question is the subcellular localization of ERManI, which has been suggested to localize to the ER membrane, the ER-derived quality control compartment (ERQC), and, surprisingly, recently to the Golgi apparatus. 25411339 1 63 theme control 198:204 arg1 I 152:152 Endoplasmic reticulum α1,2 mannosidase I 113:152 Endoplasmic reticulum α1,2 mannosidase I (ERManI) 113:161 Endoplasmic reticulum α1,2 mannosidase I (ERManI), a central component of ER quality control and ER-associated degradation (ERAD), acts as a timer enzyme, modifying N-linked sugar chains of glycoproteins with time. 25411339 1 63 theme control 198:204 arg1 component 174:182 a central component 164:182 a central component of ER quality control and ER-associated degradation (ERAD) 164:241 Endoplasmic reticulum α1,2 mannosidase I (ERManI), a central component of ER quality control and ER-associated degradation (ERAD), acts as a timer enzyme, modifying N-linked sugar chains of glycoproteins with time. 25411339 3 64 theme control 520:526 arg1 maintenance 484:494 maintenance 484:494 maintenance of glycoprotein quality control 484:526 Despite the importance of ERManI in maintenance of glycoprotein quality control, fundamental questions regarding this enzyme remain controversial. 25411339 2 65 gly glycoproteins 425:437 arg1 glycoproteins 425:437 terminally misfolded glycoproteins 404:437 terminally misfolded glycoproteins 404:437 This process halts glycoprotein folding attempts when necessary and targets terminally misfolded glycoproteins to ERAD. 25411339 5 66 theme ERAD 989:992 arg1 substrates 994:1003 ERAD substrates 989:1003 ERAD substrates 989:1003 To try to clarify this controversy, we applied a series of approaches that indicate that ERManI is located, at the steady state, in quality control vesicles (QCVs) to which ERAD substrates are transported and in which they interact with the enzyme. 25411339 1 67 theme α1,2 135:138 arg1 I 152:152 Endoplasmic reticulum α1,2 mannosidase I 113:152 Endoplasmic reticulum α1,2 mannosidase I (ERManI) 113:161 Endoplasmic reticulum α1,2 mannosidase I (ERManI), a central component of ER quality control and ER-associated degradation (ERAD), acts as a timer enzyme, modifying N-linked sugar chains of glycoproteins with time. 25411339 1 67 theme α1,2 135:138 arg1 enzyme 260:265 a timer enzyme 252:265 a timer enzyme 252:265 Endoplasmic reticulum α1,2 mannosidase I (ERManI), a central component of ER quality control and ER-associated degradation (ERAD), acts as a timer enzyme, modifying N-linked sugar chains of glycoproteins with time. 25411339 1 67 theme α1,2 135:138 arg1 component 174:182 a central component 164:182 a central component of ER quality control and ER-associated degradation (ERAD) 164:241 Endoplasmic reticulum α1,2 mannosidase I (ERManI), a central component of ER quality control and ER-associated degradation (ERAD), acts as a timer enzyme, modifying N-linked sugar chains of glycoproteins with time. 25411339 1 67 theme α1,2 135:138 arg1 ERManI 155:160 ERManI 155:160 ERManI 155:160 Endoplasmic reticulum α1,2 mannosidase I (ERManI), a central component of ER quality control and ER-associated degradation (ERAD), acts as a timer enzyme, modifying N-linked sugar chains of glycoproteins with time. 25411339 10 68 from methods 1628:1634 arg1 common 1599:1604 common 1599:1604 common 1599:1604 Of importance, we found that membrane disturbance, as is common in immunofluorescence methods, leads to an artificial appearance of ERManI in a Golgi pattern. 25411339 4 69 theme such 599:602 arg1 question 604:611 One such question 595:611 One such question 595:611 One such question is the subcellular localization of ERManI, which has been suggested to localize to the ER membrane, the ER-derived quality control compartment (ERQC), and, surprisingly, recently to the Golgi apparatus. 25411339 4 69 theme such 599:602 arg1 localization 632:643 the subcellular localization 616:643 the subcellular localization of ERManI, which has been suggested to localize to the ER membrane, the ER-derived quality control compartment (ERQC), and, surprisingly, recently to the Golgi apparatus 616:813 One such question is the subcellular localization of ERManI, which has been suggested to localize to the ER membrane, the ER-derived quality control compartment (ERQC), and, surprisingly, recently to the Golgi apparatus. 25411339 5 70 from located 915:921 arg1 QCVs 974:977 QCVs 974:977 QCVs 974:977 To try to clarify this controversy, we applied a series of approaches that indicate that ERManI is located, at the steady state, in quality control vesicles (QCVs) to which ERAD substrates are transported and in which they interact with the enzyme. 25411339 5 70 from located 915:921 arg1 vesicles 964:971 quality control vesicles 948:971 quality control vesicles (QCVs) to which ERAD substrates are transported and in which they interact with the enzyme 948:1062 To try to clarify this controversy, we applied a series of approaches that indicate that ERManI is located, at the steady state, in quality control vesicles (QCVs) to which ERAD substrates are transported and in which they interact with the enzyme. 25411339 2 71 dep folding 360:366 arg1 attempts 368:375 attempts 368:375 attempts 368:375 This process halts glycoprotein folding attempts when necessary and targets terminally misfolded glycoproteins to ERAD. 25411339 1 72 theme mannosidase 140:150 arg1 I 152:152 Endoplasmic reticulum α1,2 mannosidase I 113:152 Endoplasmic reticulum α1,2 mannosidase I (ERManI) 113:161 Endoplasmic reticulum α1,2 mannosidase I (ERManI), a central component of ER quality control and ER-associated degradation (ERAD), acts as a timer enzyme, modifying N-linked sugar chains of glycoproteins with time. 25411339 1 72 theme mannosidase 140:150 arg1 enzyme 260:265 a timer enzyme 252:265 a timer enzyme 252:265 Endoplasmic reticulum α1,2 mannosidase I (ERManI), a central component of ER quality control and ER-associated degradation (ERAD), acts as a timer enzyme, modifying N-linked sugar chains of glycoproteins with time. 25411339 1 72 theme mannosidase 140:150 arg1 component 174:182 a central component 164:182 a central component of ER quality control and ER-associated degradation (ERAD) 164:241 Endoplasmic reticulum α1,2 mannosidase I (ERManI), a central component of ER quality control and ER-associated degradation (ERAD), acts as a timer enzyme, modifying N-linked sugar chains of glycoproteins with time. 25411339 1 72 theme mannosidase 140:150 arg1 ERManI 155:160 ERManI 155:160 ERManI 155:160 Endoplasmic reticulum α1,2 mannosidase I (ERManI), a central component of ER quality control and ER-associated degradation (ERAD), acts as a timer enzyme, modifying N-linked sugar chains of glycoproteins with time. 25411339 6 73 from density 1136:1142 arg1 gradients 1157:1165 iodixanol gradients 1147:1165 iodixanol gradients 1147:1165 Both endogenous and exogenously expressed ERManI migrate at an ER-like density on iodixanol gradients, suggesting that the QCVs are derived from the ER. 25411339 1 74 theme ER-associated 210:222 arg1 ERAD 237:240 ERAD 237:240 ERAD 237:240 Endoplasmic reticulum α1,2 mannosidase I (ERManI), a central component of ER quality control and ER-associated degradation (ERAD), acts as a timer enzyme, modifying N-linked sugar chains of glycoproteins with time. 25411339 1 74 theme ER-associated 210:222 arg1 degradation 224:234 ER-associated degradation 210:234 ER-associated degradation (ERAD) 210:241 Endoplasmic reticulum α1,2 mannosidase I (ERManI), a central component of ER quality control and ER-associated degradation (ERAD), acts as a timer enzyme, modifying N-linked sugar chains of glycoproteins with time. 25411339 1 75 theme sugar 287:291 arg1 chains 293:298 N-linked sugar chains 278:298 N-linked sugar chains of glycoproteins with time 278:325 Endoplasmic reticulum α1,2 mannosidase I (ERManI), a central component of ER quality control and ER-associated degradation (ERAD), acts as a timer enzyme, modifying N-linked sugar chains of glycoproteins with time. 25411339 3 76 theme glycoprotein 499:510 arg1 control 520:526 glycoprotein quality control 499:526 glycoprotein quality control 499:526 Despite the importance of ERManI in maintenance of glycoprotein quality control, fundamental questions regarding this enzyme remain controversial. 25411339 1 77 theme degradation 224:234 arg1 I 152:152 Endoplasmic reticulum α1,2 mannosidase I 113:152 Endoplasmic reticulum α1,2 mannosidase I (ERManI) 113:161 Endoplasmic reticulum α1,2 mannosidase I (ERManI), a central component of ER quality control and ER-associated degradation (ERAD), acts as a timer enzyme, modifying N-linked sugar chains of glycoproteins with time. 25411339 1 77 theme degradation 224:234 arg1 component 174:182 a central component 164:182 a central component of ER quality control and ER-associated degradation (ERAD) 164:241 Endoplasmic reticulum α1,2 mannosidase I (ERManI), a central component of ER quality control and ER-associated degradation (ERAD), acts as a timer enzyme, modifying N-linked sugar chains of glycoproteins with time. 24728980 8 0 dep identify 1697:1704 arg1 degree 1775:1780 degree 1775:1780 degree 1775:1780 The acquired experimental data sets were then used to identify which glycans can be controlled by the media supplements and to what degree. 24728980 8 0 dep identify 1697:1704 arg1 controlled 1727:1736 controlled 1727:1736 can be controlled by the media supplements 1720:1761 The acquired experimental data sets were then used to identify which glycans can be controlled by the media supplements and to what degree. 24728980 7 1 from concentrations 1470:1483 arg1 presence 1492:1499 the presence 1488:1499 the presence of the media supplements to provide insight into the intracellular conditions that may be contributing to the changes in glycan distribution 1488:1640 We also include data indicating the glycosylation enzyme gene transcript levels as well as the intracellular nucleotide sugar concentrations in the presence of the media supplements to provide insight into the intracellular conditions that may be contributing to the changes in glycan distribution. 24728980 3 2 theme such 562:565 arg1 strategies 567:576 no such strategies 559:576 no such strategies 559:576 While an appropriately implemented on-line glycosylation control strategy during production can help to ensure a consistent glycan distribution, to date no such strategies have been reported. 24728980 7 3 theme glycan 1622:1627 arg1 distribution 1629:1640 glycan distribution 1622:1640 glycan distribution 1622:1640 We also include data indicating the glycosylation enzyme gene transcript levels as well as the intracellular nucleotide sugar concentrations in the presence of the media supplements to provide insight into the intracellular conditions that may be contributing to the changes in glycan distribution. 24728980 6 4 theme certain 1327:1333 arg1 glycans 1335:1341 certain glycans 1327:1341 certain glycans 1327:1341 Specifically, we implemented a statistically designed series of experiments to determine the significant main effects (as well as interaction effects) of media supplementation with manganese, galactose, ammonia and found that each had significant effects on certain glycans. 24728980 1 5 link N-linked 78:85 arg1 distribution 94:105 N-linked glycan distribution 78:105 N-linked glycan distribution 78:105 N-linked glycan distribution affects important end-use characteristics such as the bioactivity and efficacy of many therapeutic proteins, (including monoclonal antibodies), in vivo. 24728980 4 6 theme glycan 835:840 arg1 distribution 842:853 the glycan distribution 831:853 the glycan distribution 831:853 Our goal is to develop and validate a comprehensive strategy for effective on-line control of glycosylation, the successful achievement of which requires first identifying appropriate manipulated variables that can be used to direct the glycan distribution to a desired state. 24728980 4 7 used used 816:819 arg2 variables 794:802 appropriate manipulated variables 770:802 appropriate manipulated variables that can be used to direct the glycan distribution to a desired state 770:872 Our goal is to develop and validate a comprehensive strategy for effective on-line control of glycosylation, the successful achievement of which requires first identifying appropriate manipulated variables that can be used to direct the glycan distribution to a desired state. 24728980 7 8 theme sugar 1464:1468 arg1 concentrations 1470:1483 the intracellular nucleotide sugar concentrations 1435:1483 the glycosylation enzyme gene transcript levels as well as the intracellular nucleotide sugar concentrations in the presence of the media supplements to provide insight into the intracellular conditions that may be contributing to the changes in glycan distribution 1376:1640 We also include data indicating the glycosylation enzyme gene transcript levels as well as the intracellular nucleotide sugar concentrations in the presence of the media supplements to provide insight into the intracellular conditions that may be contributing to the changes in glycan distribution. 24728980 7 9 theme supplements 1514:1524 arg1 presence 1492:1499 the presence 1488:1499 the presence of the media supplements to provide insight into the intracellular conditions that may be contributing to the changes in glycan distribution 1488:1640 We also include data indicating the glycosylation enzyme gene transcript levels as well as the intracellular nucleotide sugar concentrations in the presence of the media supplements to provide insight into the intracellular conditions that may be contributing to the changes in glycan distribution. 24728980 6 10 theme media 1223:1227 arg1 supplementation 1229:1243 media supplementation 1223:1243 media supplementation 1223:1243 Specifically, we implemented a statistically designed series of experiments to determine the significant main effects (as well as interaction effects) of media supplementation with manganese, galactose, ammonia and found that each had significant effects on certain glycans. 24728980 4 11 theme appropriate 770:780 arg1 variables 794:802 appropriate manipulated variables 770:802 appropriate manipulated variables that can be used to direct the glycan distribution to a desired state 770:872 Our goal is to develop and validate a comprehensive strategy for effective on-line control of glycosylation, the successful achievement of which requires first identifying appropriate manipulated variables that can be used to direct the glycan distribution to a desired state. 24728980 4 12 theme comprehensive 636:648 arg1 strategy 650:657 a comprehensive strategy 634:657 a comprehensive strategy for effective on-line control of glycosylation, the successful achievement of which requires first identifying appropriate manipulated variables that can be used to direct the glycan distribution to a desired state 634:872 Our goal is to develop and validate a comprehensive strategy for effective on-line control of glycosylation, the successful achievement of which requires first identifying appropriate manipulated variables that can be used to direct the glycan distribution to a desired state. 24728980 9 13 theme manipulated 1825:1835 arg1 MnCl2 1802:1806 MnCl2 1802:1806 MnCl2 1802:1806 We determined that MnCl2 can be used as a manipulated variable to increase the relative abundance of M51 and decrease FA2 simultaneously, and galactose can be used as a manipulated variable to increase the relative abundance of FA2G1 and decrease FA2 and A2 simultaneously. 24728980 9 13 theme manipulated 1825:1835 arg1 variable 1837:1844 a manipulated variable 1823:1844 a manipulated variable 1823:1844 We determined that MnCl2 can be used as a manipulated variable to increase the relative abundance of M51 and decrease FA2 simultaneously, and galactose can be used as a manipulated variable to increase the relative abundance of FA2G1 and decrease FA2 and A2 simultaneously. 24728980 6 14 theme significant 1304:1314 arg1 effects 1316:1322 significant effects 1304:1322 significant effects 1304:1322 Specifically, we implemented a statistically designed series of experiments to determine the significant main effects (as well as interaction effects) of media supplementation with manganese, galactose, ammonia and found that each had significant effects on certain glycans. 24728980 1 15 theme N-linked 78:85 arg1 distribution 94:105 N-linked glycan distribution 78:105 N-linked glycan distribution 78:105 N-linked glycan distribution affects important end-use characteristics such as the bioactivity and efficacy of many therapeutic proteins, (including monoclonal antibodies), in vivo. 24728980 5 16 theme media 946:950 arg1 type 952:955 media type 946:955 media type 946:955 While various culture conditions such as bioreactor process variables, media type, and media supplements have been shown to affect the glycan distribution, in this study we focus on the latter. 24728980 1 17 theme many 189:192 arg1 proteins 206:213 many therapeutic proteins 189:213 many therapeutic proteins 189:213 N-linked glycan distribution affects important end-use characteristics such as the bioactivity and efficacy of many therapeutic proteins, (including monoclonal antibodies), in vivo. 24728980 8 18 used used 1689:1692 arg2 sets 1674:1677 The acquired experimental data sets 1643:1677 The acquired experimental data sets 1643:1677 The acquired experimental data sets were then used to identify which glycans can be controlled by the media supplements and to what degree. 24728980 9 19 used used 1815:1818 arg2 variable 1837:1844 a manipulated variable 1823:1844 a manipulated variable 1823:1844 We determined that MnCl2 can be used as a manipulated variable to increase the relative abundance of M51 and decrease FA2 simultaneously, and galactose can be used as a manipulated variable to increase the relative abundance of FA2G1 and decrease FA2 and A2 simultaneously. 24728980 9 19 used used 1815:1818 arg2 MnCl2 1802:1806 MnCl2 1802:1806 MnCl2 1802:1806 We determined that MnCl2 can be used as a manipulated variable to increase the relative abundance of M51 and decrease FA2 simultaneously, and galactose can be used as a manipulated variable to increase the relative abundance of FA2G1 and decrease FA2 and A2 simultaneously. 24728980 9 20 used used 1942:1945 arg2 galactose 1925:1933 galactose 1925:1933 galactose 1925:1933 We determined that MnCl2 can be used as a manipulated variable to increase the relative abundance of M51 and decrease FA2 simultaneously, and galactose can be used as a manipulated variable to increase the relative abundance of FA2G1 and decrease FA2 and A2 simultaneously. 24728980 9 20 used used 1942:1945 arg2 variable 1964:1971 a manipulated variable 1950:1971 a manipulated variable 1950:1971 We determined that MnCl2 can be used as a manipulated variable to increase the relative abundance of M51 and decrease FA2 simultaneously, and galactose can be used as a manipulated variable to increase the relative abundance of FA2G1 and decrease FA2 and A2 simultaneously. 24728980 1 21 theme glycan 87:92 arg1 distribution 94:105 N-linked glycan distribution 78:105 N-linked glycan distribution 78:105 N-linked glycan distribution affects important end-use characteristics such as the bioactivity and efficacy of many therapeutic proteins, (including monoclonal antibodies), in vivo. 24728980 1 22 theme therapeutic 194:204 arg1 proteins 206:213 many therapeutic proteins 189:213 many therapeutic proteins 189:213 N-linked glycan distribution affects important end-use characteristics such as the bioactivity and efficacy of many therapeutic proteins, (including monoclonal antibodies), in vivo. 24728980 3 23 theme on-line 441:447 arg1 strategy 471:478 an appropriately implemented on-line glycosylation control strategy 412:478 an appropriately implemented on-line glycosylation control strategy during production 412:496 While an appropriately implemented on-line glycosylation control strategy during production can help to ensure a consistent glycan distribution, to date no such strategies have been reported. 24728980 7 24 theme media 1508:1512 arg1 supplements 1514:1524 the media supplements 1504:1524 the media supplements 1504:1524 We also include data indicating the glycosylation enzyme gene transcript levels as well as the intracellular nucleotide sugar concentrations in the presence of the media supplements to provide insight into the intracellular conditions that may be contributing to the changes in glycan distribution. 24728980 8 25 theme experimental 1656:1667 arg1 sets 1674:1677 The acquired experimental data sets 1643:1677 The acquired experimental data sets 1643:1677 The acquired experimental data sets were then used to identify which glycans can be controlled by the media supplements and to what degree. 24728980 5 26 theme glycan 1010:1015 arg1 distribution 1017:1028 the glycan distribution 1006:1028 the glycan distribution 1006:1028 While various culture conditions such as bioreactor process variables, media type, and media supplements have been shown to affect the glycan distribution, in this study we focus on the latter. 24728980 7 27 from levels 1417:1422 arg1 presence 1492:1499 the presence 1488:1499 the presence of the media supplements to provide insight into the intracellular conditions that may be contributing to the changes in glycan distribution 1488:1640 We also include data indicating the glycosylation enzyme gene transcript levels as well as the intracellular nucleotide sugar concentrations in the presence of the media supplements to provide insight into the intracellular conditions that may be contributing to the changes in glycan distribution. 24728980 1 28 theme proteins 206:213 arg1 efficacy 177:184 efficacy 177:184 efficacy 177:184 N-linked glycan distribution affects important end-use characteristics such as the bioactivity and efficacy of many therapeutic proteins, (including monoclonal antibodies), in vivo. 24728980 1 28 theme proteins 206:213 arg1 bioactivity 161:171 bioactivity 161:171 bioactivity 161:171 N-linked glycan distribution affects important end-use characteristics such as the bioactivity and efficacy of many therapeutic proteins, (including monoclonal antibodies), in vivo. 24728980 3 29 theme glycosylation 449:461 arg1 strategy 471:478 an appropriately implemented on-line glycosylation control strategy 412:478 an appropriately implemented on-line glycosylation control strategy during production 412:496 While an appropriately implemented on-line glycosylation control strategy during production can help to ensure a consistent glycan distribution, to date no such strategies have been reported. 24728980 6 30 theme interaction 1199:1209 arg1 effects 1211:1217 interaction effects 1199:1217 the significant main effects (as well as interaction effects) of media supplementation with manganese, galactose, ammonia 1158:1278 Specifically, we implemented a statistically designed series of experiments to determine the significant main effects (as well as interaction effects) of media supplementation with manganese, galactose, ammonia and found that each had significant effects on certain glycans. 24728980 6 31 theme designed 1114:1121 arg1 series 1123:1128 a statistically designed series 1098:1128 a statistically designed series of experiments 1098:1143 Specifically, we implemented a statistically designed series of experiments to determine the significant main effects (as well as interaction effects) of media supplementation with manganese, galactose, ammonia and found that each had significant effects on certain glycans. 24728980 0 32 theme variables 30:38 arg1 Identification 0:13 Identification 0:13 Identification of manipulated variables for a glycosylation control strategy. 0:76 Identification of manipulated variables for a glycosylation control strategy. 24728980 5 33 theme various 881:887 arg1 media 962:966 media 962:966 media 962:966 While various culture conditions such as bioreactor process variables, media type, and media supplements have been shown to affect the glycan distribution, in this study we focus on the latter. 24728980 5 33 theme various 881:887 arg1 type 952:955 media type 946:955 media type 946:955 While various culture conditions such as bioreactor process variables, media type, and media supplements have been shown to affect the glycan distribution, in this study we focus on the latter. 24728980 5 33 theme various 881:887 arg1 variables 935:943 bioreactor process variables 916:943 bioreactor process variables 916:943 While various culture conditions such as bioreactor process variables, media type, and media supplements have been shown to affect the glycan distribution, in this study we focus on the latter. 24728980 5 33 theme various 881:887 arg1 conditions 897:906 various culture conditions 881:906 various culture conditions such as bioreactor process variables, media type, and media supplements 881:978 While various culture conditions such as bioreactor process variables, media type, and media supplements have been shown to affect the glycan distribution, in this study we focus on the latter. 24728980 7 34 from changes 1611:1617 arg1 distribution 1629:1640 glycan distribution 1622:1640 glycan distribution 1622:1640 We also include data indicating the glycosylation enzyme gene transcript levels as well as the intracellular nucleotide sugar concentrations in the presence of the media supplements to provide insight into the intracellular conditions that may be contributing to the changes in glycan distribution. 24728980 1 35 dep bioactivity 161:171 arg1 the 157:159 the 157:159 the 157:159 N-linked glycan distribution affects important end-use characteristics such as the bioactivity and efficacy of many therapeutic proteins, (including monoclonal antibodies), in vivo. 24728980 3 36 theme glycan 530:535 arg1 distribution 537:548 a consistent glycan distribution 517:548 a consistent glycan distribution 517:548 While an appropriately implemented on-line glycosylation control strategy during production can help to ensure a consistent glycan distribution, to date no such strategies have been reported. 24728980 0 37 theme manipulated 18:28 arg1 variables 30:38 manipulated variables 18:38 manipulated variables for a glycosylation control strategy 18:75 Identification of manipulated variables for a glycosylation control strategy. 24728980 2 38 theme glycan 283:288 arg1 distributions 290:302 desired glycan distributions 275:302 desired glycan distributions 275:302 Yet, obtaining desired glycan distributions consistently during batch-to-batch production can be challenging for biopharmaceutical manufacturers. 24728980 7 39 theme nucleotide 1453:1462 arg1 concentrations 1470:1483 the intracellular nucleotide sugar concentrations 1435:1483 the glycosylation enzyme gene transcript levels as well as the intracellular nucleotide sugar concentrations in the presence of the media supplements to provide insight into the intracellular conditions that may be contributing to the changes in glycan distribution 1376:1640 We also include data indicating the glycosylation enzyme gene transcript levels as well as the intracellular nucleotide sugar concentrations in the presence of the media supplements to provide insight into the intracellular conditions that may be contributing to the changes in glycan distribution. 24728980 6 40 contain had 1300:1302 arg1 each 1295:1298 each 1295:1298 each 1295:1298 Specifically, we implemented a statistically designed series of experiments to determine the significant main effects (as well as interaction effects) of media supplementation with manganese, galactose, ammonia and found that each had significant effects on certain glycans. 24728980 6 40 contain had 1300:1302 arg2 effects 1316:1322 significant effects 1304:1322 significant effects 1304:1322 Specifically, we implemented a statistically designed series of experiments to determine the significant main effects (as well as interaction effects) of media supplementation with manganese, galactose, ammonia and found that each had significant effects on certain glycans. 24728980 6 41 theme significant 1162:1172 arg1 effects 1179:1185 the significant main effects 1158:1185 the significant main effects (as well as interaction effects) of media supplementation with manganese, galactose, ammonia 1158:1278 Specifically, we implemented a statistically designed series of experiments to determine the significant main effects (as well as interaction effects) of media supplementation with manganese, galactose, ammonia and found that each had significant effects on certain glycans. 24728980 8 42 theme acquired 1647:1654 arg1 sets 1674:1677 The acquired experimental data sets 1643:1677 The acquired experimental data sets 1643:1677 The acquired experimental data sets were then used to identify which glycans can be controlled by the media supplements and to what degree. 24728980 5 43 theme bioreactor 916:925 arg1 variables 935:943 bioreactor process variables 916:943 bioreactor process variables 916:943 While various culture conditions such as bioreactor process variables, media type, and media supplements have been shown to affect the glycan distribution, in this study we focus on the latter. 24728980 1 44 dep proteins 206:213 arg1 including 217:225 including 217:225 including monoclonal antibodies 217:247 N-linked glycan distribution affects important end-use characteristics such as the bioactivity and efficacy of many therapeutic proteins, (including monoclonal antibodies), in vivo. 24728980 1 45 theme important 115:123 arg1 characteristics 133:147 important end-use characteristics 115:147 important end-use characteristics such as the bioactivity and efficacy of many therapeutic proteins, (including monoclonal antibodies), in vivo 115:257 N-linked glycan distribution affects important end-use characteristics such as the bioactivity and efficacy of many therapeutic proteins, (including monoclonal antibodies), in vivo. 24728980 1 45 theme important 115:123 arg1 efficacy 177:184 efficacy 177:184 efficacy 177:184 N-linked glycan distribution affects important end-use characteristics such as the bioactivity and efficacy of many therapeutic proteins, (including monoclonal antibodies), in vivo. 24728980 1 45 theme important 115:123 arg1 bioactivity 161:171 bioactivity 161:171 bioactivity 161:171 N-linked glycan distribution affects important end-use characteristics such as the bioactivity and efficacy of many therapeutic proteins, (including monoclonal antibodies), in vivo. 24728980 1 46 theme monoclonal 227:236 arg1 antibodies 238:247 monoclonal antibodies 227:247 monoclonal antibodies 227:247 N-linked glycan distribution affects important end-use characteristics such as the bioactivity and efficacy of many therapeutic proteins, (including monoclonal antibodies), in vivo. 24728980 6 47 theme experiments 1133:1143 arg1 series 1123:1128 a statistically designed series 1098:1128 a statistically designed series of experiments 1098:1143 Specifically, we implemented a statistically designed series of experiments to determine the significant main effects (as well as interaction effects) of media supplementation with manganese, galactose, ammonia and found that each had significant effects on certain glycans. 24728980 7 48 theme intracellular 1439:1451 arg1 concentrations 1470:1483 the intracellular nucleotide sugar concentrations 1435:1483 the glycosylation enzyme gene transcript levels as well as the intracellular nucleotide sugar concentrations in the presence of the media supplements to provide insight into the intracellular conditions that may be contributing to the changes in glycan distribution 1376:1640 We also include data indicating the glycosylation enzyme gene transcript levels as well as the intracellular nucleotide sugar concentrations in the presence of the media supplements to provide insight into the intracellular conditions that may be contributing to the changes in glycan distribution. 24728980 5 49 theme culture 889:895 arg1 media 962:966 media 962:966 media 962:966 While various culture conditions such as bioreactor process variables, media type, and media supplements have been shown to affect the glycan distribution, in this study we focus on the latter. 24728980 5 49 theme culture 889:895 arg1 type 952:955 media type 946:955 media type 946:955 While various culture conditions such as bioreactor process variables, media type, and media supplements have been shown to affect the glycan distribution, in this study we focus on the latter. 24728980 5 49 theme culture 889:895 arg1 variables 935:943 bioreactor process variables 916:943 bioreactor process variables 916:943 While various culture conditions such as bioreactor process variables, media type, and media supplements have been shown to affect the glycan distribution, in this study we focus on the latter. 24728980 5 49 theme culture 889:895 arg1 conditions 897:906 various culture conditions 881:906 various culture conditions such as bioreactor process variables, media type, and media supplements 881:978 While various culture conditions such as bioreactor process variables, media type, and media supplements have been shown to affect the glycan distribution, in this study we focus on the latter. 24728980 9 50 theme relative 1989:1996 arg1 abundance 1998:2006 the relative abundance 1985:2006 the relative abundance of FA2G1 1985:2015 We determined that MnCl2 can be used as a manipulated variable to increase the relative abundance of M51 and decrease FA2 simultaneously, and galactose can be used as a manipulated variable to increase the relative abundance of FA2G1 and decrease FA2 and A2 simultaneously. 24728980 3 51 theme consistent 519:528 arg1 distribution 537:548 a consistent glycan distribution 517:548 a consistent glycan distribution 517:548 While an appropriately implemented on-line glycosylation control strategy during production can help to ensure a consistent glycan distribution, to date no such strategies have been reported. 24728980 0 52 theme control 60:66 arg1 strategy 68:75 a glycosylation control strategy 44:75 a glycosylation control strategy 44:75 Identification of manipulated variables for a glycosylation control strategy. 24728980 9 53 theme relative 1862:1869 arg1 abundance 1871:1879 the relative abundance 1858:1879 the relative abundance of M51 1858:1886 We determined that MnCl2 can be used as a manipulated variable to increase the relative abundance of M51 and decrease FA2 simultaneously, and galactose can be used as a manipulated variable to increase the relative abundance of FA2G1 and decrease FA2 and A2 simultaneously. 24728980 9 54 theme M51 1884:1886 arg1 abundance 1871:1879 the relative abundance 1858:1879 the relative abundance of M51 1858:1886 We determined that MnCl2 can be used as a manipulated variable to increase the relative abundance of M51 and decrease FA2 simultaneously, and galactose can be used as a manipulated variable to increase the relative abundance of FA2G1 and decrease FA2 and A2 simultaneously. 24728980 5 55 dep variables 935:943 arg1 supplements 968:978 supplements 968:978 supplements 968:978 While various culture conditions such as bioreactor process variables, media type, and media supplements have been shown to affect the glycan distribution, in this study we focus on the latter. 24728980 2 56 theme biopharmaceutical 373:389 arg1 manufacturers 391:403 biopharmaceutical manufacturers 373:403 biopharmaceutical manufacturers 373:403 Yet, obtaining desired glycan distributions consistently during batch-to-batch production can be challenging for biopharmaceutical manufacturers. 24728980 0 57 theme glycosylation 46:58 arg1 strategy 68:75 a glycosylation control strategy 44:75 a glycosylation control strategy 44:75 Identification of manipulated variables for a glycosylation control strategy. 24728980 6 58 with effects 1211:1217 arg1 ammonia 1272:1278 ammonia 1272:1278 ammonia 1272:1278 Specifically, we implemented a statistically designed series of experiments to determine the significant main effects (as well as interaction effects) of media supplementation with manganese, galactose, ammonia and found that each had significant effects on certain glycans. 24728980 6 58 with effects 1211:1217 arg1 galactose 1261:1269 galactose 1261:1269 galactose 1261:1269 Specifically, we implemented a statistically designed series of experiments to determine the significant main effects (as well as interaction effects) of media supplementation with manganese, galactose, ammonia and found that each had significant effects on certain glycans. 24728980 6 58 with effects 1211:1217 arg1 manganese 1250:1258 manganese 1250:1258 manganese 1250:1258 Specifically, we implemented a statistically designed series of experiments to determine the significant main effects (as well as interaction effects) of media supplementation with manganese, galactose, ammonia and found that each had significant effects on certain glycans. 24728980 7 59 theme glycosylation 1380:1392 arg1 levels 1417:1422 the glycosylation enzyme gene transcript levels 1376:1422 the glycosylation enzyme gene transcript levels as well as the intracellular nucleotide sugar concentrations in the presence of the media supplements to provide insight into the intracellular conditions that may be contributing to the changes in glycan distribution 1376:1640 We also include data indicating the glycosylation enzyme gene transcript levels as well as the intracellular nucleotide sugar concentrations in the presence of the media supplements to provide insight into the intracellular conditions that may be contributing to the changes in glycan distribution. 24728980 4 60 theme manipulated 782:792 arg1 variables 794:802 appropriate manipulated variables 770:802 appropriate manipulated variables that can be used to direct the glycan distribution to a desired state 770:872 Our goal is to develop and validate a comprehensive strategy for effective on-line control of glycosylation, the successful achievement of which requires first identifying appropriate manipulated variables that can be used to direct the glycan distribution to a desired state. 24728980 7 61 theme gene 1401:1404 arg1 levels 1417:1422 the glycosylation enzyme gene transcript levels 1376:1422 the glycosylation enzyme gene transcript levels as well as the intracellular nucleotide sugar concentrations in the presence of the media supplements to provide insight into the intracellular conditions that may be contributing to the changes in glycan distribution 1376:1640 We also include data indicating the glycosylation enzyme gene transcript levels as well as the intracellular nucleotide sugar concentrations in the presence of the media supplements to provide insight into the intracellular conditions that may be contributing to the changes in glycan distribution. 24728980 7 62 theme transcript 1406:1415 arg1 levels 1417:1422 the glycosylation enzyme gene transcript levels 1376:1422 the glycosylation enzyme gene transcript levels as well as the intracellular nucleotide sugar concentrations in the presence of the media supplements to provide insight into the intracellular conditions that may be contributing to the changes in glycan distribution 1376:1640 We also include data indicating the glycosylation enzyme gene transcript levels as well as the intracellular nucleotide sugar concentrations in the presence of the media supplements to provide insight into the intracellular conditions that may be contributing to the changes in glycan distribution. 24728980 4 63 theme desired 860:866 arg1 state 868:872 a desired state 858:872 a desired state 858:872 Our goal is to develop and validate a comprehensive strategy for effective on-line control of glycosylation, the successful achievement of which requires first identifying appropriate manipulated variables that can be used to direct the glycan distribution to a desired state. 24728980 9 64 theme FA2G1 2011:2015 arg1 abundance 1998:2006 the relative abundance 1985:2006 the relative abundance of FA2G1 1985:2015 We determined that MnCl2 can be used as a manipulated variable to increase the relative abundance of M51 and decrease FA2 simultaneously, and galactose can be used as a manipulated variable to increase the relative abundance of FA2G1 and decrease FA2 and A2 simultaneously. 24728980 2 65 theme batch-to-batch 324:337 arg1 production 339:348 batch-to-batch production 324:348 batch-to-batch production 324:348 Yet, obtaining desired glycan distributions consistently during batch-to-batch production can be challenging for biopharmaceutical manufacturers. 24728980 4 66 theme effective 663:671 arg1 control 681:687 effective on-line control 663:687 effective on-line control 663:687 Our goal is to develop and validate a comprehensive strategy for effective on-line control of glycosylation, the successful achievement of which requires first identifying appropriate manipulated variables that can be used to direct the glycan distribution to a desired state. 24728980 2 67 theme desired 275:281 arg1 distributions 290:302 desired glycan distributions 275:302 desired glycan distributions 275:302 Yet, obtaining desired glycan distributions consistently during batch-to-batch production can be challenging for biopharmaceutical manufacturers. 24728980 7 68 theme intracellular 1554:1566 arg1 conditions 1568:1577 the intracellular conditions 1550:1577 the intracellular conditions that may be contributing to the changes in glycan distribution 1550:1640 We also include data indicating the glycosylation enzyme gene transcript levels as well as the intracellular nucleotide sugar concentrations in the presence of the media supplements to provide insight into the intracellular conditions that may be contributing to the changes in glycan distribution. 24728980 6 69 theme supplementation 1229:1243 arg1 effects 1179:1185 the significant main effects 1158:1185 the significant main effects (as well as interaction effects) of media supplementation with manganese, galactose, ammonia 1158:1278 Specifically, we implemented a statistically designed series of experiments to determine the significant main effects (as well as interaction effects) of media supplementation with manganese, galactose, ammonia and found that each had significant effects on certain glycans. 24728980 6 69 theme supplementation 1229:1243 arg1 effects 1211:1217 interaction effects 1199:1217 the significant main effects (as well as interaction effects) of media supplementation with manganese, galactose, ammonia 1158:1278 Specifically, we implemented a statistically designed series of experiments to determine the significant main effects (as well as interaction effects) of media supplementation with manganese, galactose, ammonia and found that each had significant effects on certain glycans. 24728980 6 70 theme main 1174:1177 arg1 effects 1179:1185 the significant main effects 1158:1185 the significant main effects (as well as interaction effects) of media supplementation with manganese, galactose, ammonia 1158:1278 Specifically, we implemented a statistically designed series of experiments to determine the significant main effects (as well as interaction effects) of media supplementation with manganese, galactose, ammonia and found that each had significant effects on certain glycans. 24728980 9 71 theme manipulated 1952:1962 arg1 galactose 1925:1933 galactose 1925:1933 galactose 1925:1933 We determined that MnCl2 can be used as a manipulated variable to increase the relative abundance of M51 and decrease FA2 simultaneously, and galactose can be used as a manipulated variable to increase the relative abundance of FA2G1 and decrease FA2 and A2 simultaneously. 24728980 9 71 theme manipulated 1952:1962 arg1 variable 1964:1971 a manipulated variable 1950:1971 a manipulated variable 1950:1971 We determined that MnCl2 can be used as a manipulated variable to increase the relative abundance of M51 and decrease FA2 simultaneously, and galactose can be used as a manipulated variable to increase the relative abundance of FA2G1 and decrease FA2 and A2 simultaneously. 24728980 8 72 theme data 1669:1672 arg1 sets 1674:1677 The acquired experimental data sets 1643:1677 The acquired experimental data sets 1643:1677 The acquired experimental data sets were then used to identify which glycans can be controlled by the media supplements and to what degree. 24728980 8 73 theme media 1745:1749 arg1 supplements 1751:1761 the media supplements 1741:1761 the media supplements 1741:1761 The acquired experimental data sets were then used to identify which glycans can be controlled by the media supplements and to what degree. 24728980 5 74 theme process 927:933 arg1 variables 935:943 bioreactor process variables 916:943 bioreactor process variables 916:943 While various culture conditions such as bioreactor process variables, media type, and media supplements have been shown to affect the glycan distribution, in this study we focus on the latter. 24728980 7 75 theme enzyme 1394:1399 arg1 levels 1417:1422 the glycosylation enzyme gene transcript levels 1376:1422 the glycosylation enzyme gene transcript levels as well as the intracellular nucleotide sugar concentrations in the presence of the media supplements to provide insight into the intracellular conditions that may be contributing to the changes in glycan distribution 1376:1640 We also include data indicating the glycosylation enzyme gene transcript levels as well as the intracellular nucleotide sugar concentrations in the presence of the media supplements to provide insight into the intracellular conditions that may be contributing to the changes in glycan distribution. 24728980 4 76 theme glycosylation 692:704 arg1 control 681:687 effective on-line control 663:687 effective on-line control 663:687 Our goal is to develop and validate a comprehensive strategy for effective on-line control of glycosylation, the successful achievement of which requires first identifying appropriate manipulated variables that can be used to direct the glycan distribution to a desired state. 24728980 1 77 dep important 115:123 arg1 end-use 125:131 end-use 125:131 end-use 125:131 N-linked glycan distribution affects important end-use characteristics such as the bioactivity and efficacy of many therapeutic proteins, (including monoclonal antibodies), in vivo. 24728980 4 78 theme successful 711:720 arg1 achievement 722:732 the successful achievement 707:732 the successful achievement 707:732 Our goal is to develop and validate a comprehensive strategy for effective on-line control of glycosylation, the successful achievement of which requires first identifying appropriate manipulated variables that can be used to direct the glycan distribution to a desired state. 24728980 4 79 theme control 681:687 arg1 achievement 722:732 the successful achievement 707:732 the successful achievement 707:732 Our goal is to develop and validate a comprehensive strategy for effective on-line control of glycosylation, the successful achievement of which requires first identifying appropriate manipulated variables that can be used to direct the glycan distribution to a desired state. 24728980 3 80 theme control 463:469 arg1 strategy 471:478 an appropriately implemented on-line glycosylation control strategy 412:478 an appropriately implemented on-line glycosylation control strategy during production 412:496 While an appropriately implemented on-line glycosylation control strategy during production can help to ensure a consistent glycan distribution, to date no such strategies have been reported. 24728980 6 81 with effects 1179:1185 arg1 ammonia 1272:1278 ammonia 1272:1278 ammonia 1272:1278 Specifically, we implemented a statistically designed series of experiments to determine the significant main effects (as well as interaction effects) of media supplementation with manganese, galactose, ammonia and found that each had significant effects on certain glycans. 24728980 6 81 with effects 1179:1185 arg1 galactose 1261:1269 galactose 1261:1269 galactose 1261:1269 Specifically, we implemented a statistically designed series of experiments to determine the significant main effects (as well as interaction effects) of media supplementation with manganese, galactose, ammonia and found that each had significant effects on certain glycans. 24728980 6 81 with effects 1179:1185 arg1 manganese 1250:1258 manganese 1250:1258 manganese 1250:1258 Specifically, we implemented a statistically designed series of experiments to determine the significant main effects (as well as interaction effects) of media supplementation with manganese, galactose, ammonia and found that each had significant effects on certain glycans. 24728980 3 82 theme implemented 429:439 arg1 strategy 471:478 an appropriately implemented on-line glycosylation control strategy 412:478 an appropriately implemented on-line glycosylation control strategy during production 412:496 While an appropriately implemented on-line glycosylation control strategy during production can help to ensure a consistent glycan distribution, to date no such strategies have been reported. 24728980 4 83 theme on-line 673:679 arg1 control 681:687 effective on-line control 663:687 effective on-line control 663:687 Our goal is to develop and validate a comprehensive strategy for effective on-line control of glycosylation, the successful achievement of which requires first identifying appropriate manipulated variables that can be used to direct the glycan distribution to a desired state. 24619407 3 0 theme asialoglycoprotein 508:525 arg1 receptor 527:534 the asialoglycoprotein receptor 504:534 the asialoglycoprotein receptor (ASGR) 504:541 Two highly abundant, carbohydrate-specific, endocytic receptors, the asialoglycoprotein receptor (ASGR) and the mannose receptor (ManR) are expressed in the liver by parenchymal and sinusoidal endothelial cells, respectively. 24619407 3 0 theme asialoglycoprotein 508:525 arg1 receptors 493:501 Two highly abundant, carbohydrate-specific, endocytic receptors 439:501 Two highly abundant, carbohydrate-specific, endocytic receptors 439:501 Two highly abundant, carbohydrate-specific, endocytic receptors, the asialoglycoprotein receptor (ASGR) and the mannose receptor (ManR) are expressed in the liver by parenchymal and sinusoidal endothelial cells, respectively. 24619407 3 0 theme asialoglycoprotein 508:525 arg1 ASGR 537:540 ASGR 537:540 ASGR 537:540 Two highly abundant, carbohydrate-specific, endocytic receptors, the asialoglycoprotein receptor (ASGR) and the mannose receptor (ManR) are expressed in the liver by parenchymal and sinusoidal endothelial cells, respectively. 24619407 4 1 theme β1,4-linked 789:799 arg1 GalNAc-4-SO4 801:812 β1,4-linked GalNAc-4-SO4 789:812 β1,4-linked GalNAc-4-SO4 789:812 We demonstrate that the ManR mediates the clearance of glycoproteins such as LH that bear N-linked glycans terminating with β1,4-linked GalNAc-4-SO4, as well as glycoproteins bearing glycans that terminate with Man. 24619407 0 2 from points 119:124 arg1 cycle 146:150 the reproductive cycle 129:150 the reproductive cycle 129:150 Modulation of mannose and asialoglycoprotein receptor expression determines glycoprotein hormone half-life at critical points in the reproductive cycle. 24619407 3 3 theme endothelial 632:642 arg1 cells 644:648 parenchymal and sinusoidal endothelial cells 605:648 parenchymal and sinusoidal endothelial cells 605:648 Two highly abundant, carbohydrate-specific, endocytic receptors, the asialoglycoprotein receptor (ASGR) and the mannose receptor (ManR) are expressed in the liver by parenchymal and sinusoidal endothelial cells, respectively. 24619407 9 4 theme reduced 1367:1373 arg1 expression 1375:1384 reduced expression 1367:1384 reduced expression of the ManR at the time of sexual maturation 1367:1429 Thus, reduced expression of the ManR at the time of sexual maturation will increase the potency of LH in vivo, whereas increased expression during pregnancy will reduce LH potency until progesterone and receptor levels fall prior to parturition. 24619407 7 5 theme ASGR 1172:1175 arg1 mRNA 1177:1180 ASGR mRNA 1172:1180 ASGR mRNA 1172:1180 In contrast, ManR mRNA, but not ASGR mRNA, decreases in male mice at the time of sexual maturation. 24619407 9 6 theme receptor 1564:1571 arg1 levels 1573:1578 progesterone and receptor levels 1547:1578 progesterone and receptor levels 1547:1578 Thus, reduced expression of the ManR at the time of sexual maturation will increase the potency of LH in vivo, whereas increased expression during pregnancy will reduce LH potency until progesterone and receptor levels fall prior to parturition. 24619407 0 7 gly glycoprotein 76:87 arg1 glycoprotein 76:87 glycoprotein hormone half-life 76:105 glycoprotein hormone half-life 76:105 Modulation of mannose and asialoglycoprotein receptor expression determines glycoprotein hormone half-life at critical points in the reproductive cycle. 24619407 5 8 from progesterone 957:968 arg1 mice 982:985 pregnant mice 973:985 pregnant mice 973:985 Steady state levels of mRNA encoding the ASGR and the ManR are regulated by progesterone in pregnant mice, reaching maximal levels on day 12.5 of pregnancy. 24619407 0 9 theme critical 110:117 arg1 points 119:124 critical points 110:124 critical points in the reproductive cycle 110:150 Modulation of mannose and asialoglycoprotein receptor expression determines glycoprotein hormone half-life at critical points in the reproductive cycle. 24619407 8 10 theme expression 1277:1286 arg1 levels 1253:1258 levels 1253:1258 levels of ManR and ASGR expression 1253:1286 We show that levels of ManR and ASGR expression control the clearance rate for glycoproteins bearing recognized glycans. 24619407 3 11 theme mannose 551:557 arg1 ManR 569:572 ManR 569:572 ManR 569:572 Two highly abundant, carbohydrate-specific, endocytic receptors, the asialoglycoprotein receptor (ASGR) and the mannose receptor (ManR) are expressed in the liver by parenchymal and sinusoidal endothelial cells, respectively. 24619407 3 11 theme mannose 551:557 arg1 receptors 493:501 Two highly abundant, carbohydrate-specific, endocytic receptors 439:501 Two highly abundant, carbohydrate-specific, endocytic receptors 439:501 Two highly abundant, carbohydrate-specific, endocytic receptors, the asialoglycoprotein receptor (ASGR) and the mannose receptor (ManR) are expressed in the liver by parenchymal and sinusoidal endothelial cells, respectively. 24619407 3 11 theme mannose 551:557 arg1 receptor 559:566 the mannose receptor 547:566 the mannose receptor (ManR) 547:573 Two highly abundant, carbohydrate-specific, endocytic receptors, the asialoglycoprotein receptor (ASGR) and the mannose receptor (ManR) are expressed in the liver by parenchymal and sinusoidal endothelial cells, respectively. 24619407 6 12 theme pregnant 1125:1132 arg1 mice 1134:1137 pregnant mice 1125:1137 pregnant mice 1125:1137 Protein expression and glycan-specific binding activity also increase in the livers of pregnant mice. 24619407 8 13 theme clearance 1300:1308 arg1 rate 1310:1313 the clearance rate 1296:1313 the clearance rate for glycoproteins bearing recognized glycans 1296:1358 We show that levels of ManR and ASGR expression control the clearance rate for glycoproteins bearing recognized glycans. 24619407 6 14 theme binding 1077:1083 arg1 activity 1085:1092 glycan-specific binding activity 1061:1092 glycan-specific binding activity 1061:1092 Protein expression and glycan-specific binding activity also increase in the livers of pregnant mice. 24619407 5 15 theme mRNA 904:907 arg1 levels 894:899 Steady state levels 881:899 Steady state levels of mRNA encoding the ASGR and the ManR 881:938 Steady state levels of mRNA encoding the ASGR and the ManR are regulated by progesterone in pregnant mice, reaching maximal levels on day 12.5 of pregnancy. 24619407 3 16 gly asialoglycoprotein 508:525 arg1 asialoglycoprotein 508:525 the asialoglycoprotein receptor 504:534 the asialoglycoprotein receptor (ASGR) 504:541 Two highly abundant, carbohydrate-specific, endocytic receptors, the asialoglycoprotein receptor (ASGR) and the mannose receptor (ManR) are expressed in the liver by parenchymal and sinusoidal endothelial cells, respectively. 24619407 6 17 theme glycan-specific 1061:1075 arg1 activity 1085:1092 glycan-specific binding activity 1061:1092 glycan-specific binding activity 1061:1092 Protein expression and glycan-specific binding activity also increase in the livers of pregnant mice. 24619407 2 18 theme regulated 375:383 arg1 release 385:391 regulated release 375:391 regulated release into the circulation 375:412 We have shown that clearance rates for glycoproteins such as luteinizing hormone (LH) that undergo regulated release into the circulation determine their potency. 24619407 8 19 gly glycoproteins 1319:1331 arg1 glycoproteins 1319:1331 glycoproteins 1319:1331 glycoproteins bearing recognized glycans 1319:1358 We show that levels of ManR and ASGR expression control the clearance rate for glycoproteins bearing recognized glycans. 24619407 5 20 theme Steady 881:886 arg1 levels 894:899 Steady state levels 881:899 Steady state levels of mRNA encoding the ASGR and the ManR 881:938 Steady state levels of mRNA encoding the ASGR and the ManR are regulated by progesterone in pregnant mice, reaching maximal levels on day 12.5 of pregnancy. 24619407 9 21 theme progesterone 1547:1558 arg1 levels 1573:1578 progesterone and receptor levels 1547:1578 progesterone and receptor levels 1547:1578 Thus, reduced expression of the ManR at the time of sexual maturation will increase the potency of LH in vivo, whereas increased expression during pregnancy will reduce LH potency until progesterone and receptor levels fall prior to parturition. 24619407 9 22 dep increase 1436:1443 arg1 whereas 1472:1478 whereas 1472:1478 whereas 1472:1478 Thus, reduced expression of the ManR at the time of sexual maturation will increase the potency of LH in vivo, whereas increased expression during pregnancy will reduce LH potency until progesterone and receptor levels fall prior to parturition. 24619407 6 23 theme Protein 1038:1044 arg1 expression 1046:1055 Protein expression 1038:1055 Protein expression 1038:1055 Protein expression and glycan-specific binding activity also increase in the livers of pregnant mice. 24619407 0 24 theme mannose 14:20 arg1 expression 54:63 mannose and asialoglycoprotein receptor expression 14:63 expression 54:63 Modulation of mannose and asialoglycoprotein receptor expression determines glycoprotein hormone half-life at critical points in the reproductive cycle. 24619407 9 25 theme sexual 1413:1418 arg1 maturation 1420:1429 sexual maturation 1413:1429 sexual maturation 1413:1429 Thus, reduced expression of the ManR at the time of sexual maturation will increase the potency of LH in vivo, whereas increased expression during pregnancy will reduce LH potency until progesterone and receptor levels fall prior to parturition. 24619407 0 26 theme reproductive 133:144 arg1 cycle 146:150 the reproductive cycle 129:150 the reproductive cycle 129:150 Modulation of mannose and asialoglycoprotein receptor expression determines glycoprotein hormone half-life at critical points in the reproductive cycle. 24619407 2 27 theme clearance 295:303 arg1 rates 305:309 clearance rates 295:309 clearance rates for glycoproteins such as luteinizing hormone (LH) that undergo regulated release into the circulation 295:412 We have shown that clearance rates for glycoproteins such as luteinizing hormone (LH) that undergo regulated release into the circulation determine their potency. 24619407 8 28 theme ManR 1263:1266 arg1 levels 1253:1258 levels 1253:1258 levels of ManR and ASGR expression 1253:1286 We show that levels of ManR and ASGR expression control the clearance rate for glycoproteins bearing recognized glycans. 24619407 0 29 theme receptor 45:52 arg1 expression 54:63 mannose and asialoglycoprotein receptor expression 14:63 expression 54:63 Modulation of mannose and asialoglycoprotein receptor expression determines glycoprotein hormone half-life at critical points in the reproductive cycle. 24619407 1 30 from activity 258:265 arg1 vivo 270:273 vivo 270:273 vivo 270:273 The rate at which glycoproteins are cleared from the circulation has a critical impact on their biologic activity in vivo. 24619407 4 31 link β1,4-linked 789:799 arg1 GalNAc-4-SO4 801:812 β1,4-linked GalNAc-4-SO4 789:812 β1,4-linked GalNAc-4-SO4 789:812 We demonstrate that the ManR mediates the clearance of glycoproteins such as LH that bear N-linked glycans terminating with β1,4-linked GalNAc-4-SO4, as well as glycoproteins bearing glycans that terminate with Man. 24619407 9 32 theme LH 1530:1531 arg1 potency 1533:1539 LH potency 1530:1539 LH potency 1530:1539 Thus, reduced expression of the ManR at the time of sexual maturation will increase the potency of LH in vivo, whereas increased expression during pregnancy will reduce LH potency until progesterone and receptor levels fall prior to parturition. 24619407 3 33 theme abundant 450:457 arg1 receptor 527:534 the asialoglycoprotein receptor 504:534 the asialoglycoprotein receptor (ASGR) 504:541 Two highly abundant, carbohydrate-specific, endocytic receptors, the asialoglycoprotein receptor (ASGR) and the mannose receptor (ManR) are expressed in the liver by parenchymal and sinusoidal endothelial cells, respectively. 24619407 3 33 theme abundant 450:457 arg1 receptors 493:501 Two highly abundant, carbohydrate-specific, endocytic receptors 439:501 Two highly abundant, carbohydrate-specific, endocytic receptors 439:501 Two highly abundant, carbohydrate-specific, endocytic receptors, the asialoglycoprotein receptor (ASGR) and the mannose receptor (ManR) are expressed in the liver by parenchymal and sinusoidal endothelial cells, respectively. 24619407 3 33 theme abundant 450:457 arg1 receptor 559:566 the mannose receptor 547:566 the mannose receptor (ManR) 547:573 Two highly abundant, carbohydrate-specific, endocytic receptors, the asialoglycoprotein receptor (ASGR) and the mannose receptor (ManR) are expressed in the liver by parenchymal and sinusoidal endothelial cells, respectively. 24619407 0 34 theme asialoglycoprotein 26:43 arg1 expression 54:63 mannose and asialoglycoprotein receptor expression 14:63 expression 54:63 Modulation of mannose and asialoglycoprotein receptor expression determines glycoprotein hormone half-life at critical points in the reproductive cycle. 24619407 4 35 gly glycoproteins 720:732 arg1 LH 742:743 LH 742:743 LH that bear N-linked glycans terminating with β1,4-linked GalNAc-4-SO4 742:812 We demonstrate that the ManR mediates the clearance of glycoproteins such as LH that bear N-linked glycans terminating with β1,4-linked GalNAc-4-SO4, as well as glycoproteins bearing glycans that terminate with Man. 24619407 4 35 gly glycoproteins 720:732 arg1 glycoproteins 720:732 glycoproteins 720:732 glycoproteins such as LH that bear N-linked glycans terminating with β1,4-linked GalNAc-4-SO4 720:812 We demonstrate that the ManR mediates the clearance of glycoproteins such as LH that bear N-linked glycans terminating with β1,4-linked GalNAc-4-SO4, as well as glycoproteins bearing glycans that terminate with Man. 24619407 3 36 theme sinusoidal 621:630 arg1 cells 644:648 parenchymal and sinusoidal endothelial cells 605:648 parenchymal and sinusoidal endothelial cells 605:648 Two highly abundant, carbohydrate-specific, endocytic receptors, the asialoglycoprotein receptor (ASGR) and the mannose receptor (ManR) are expressed in the liver by parenchymal and sinusoidal endothelial cells, respectively. 24619407 8 37 theme recognized 1341:1350 arg1 glycans 1352:1358 recognized glycans 1341:1358 recognized glycans 1341:1358 We show that levels of ManR and ASGR expression control the clearance rate for glycoproteins bearing recognized glycans. 24619407 1 38 theme critical 224:231 arg1 impact 233:238 a critical impact 222:238 a critical impact 222:238 The rate at which glycoproteins are cleared from the circulation has a critical impact on their biologic activity in vivo. 24619407 9 39 theme ManR 1393:1396 arg1 expression 1375:1384 reduced expression 1367:1384 reduced expression of the ManR at the time of sexual maturation 1367:1429 Thus, reduced expression of the ManR at the time of sexual maturation will increase the potency of LH in vivo, whereas increased expression during pregnancy will reduce LH potency until progesterone and receptor levels fall prior to parturition. 24619407 0 40 theme glycoprotein 76:87 arg1 half-life 97:105 glycoprotein hormone half-life 76:105 glycoprotein hormone half-life 76:105 Modulation of mannose and asialoglycoprotein receptor expression determines glycoprotein hormone half-life at critical points in the reproductive cycle. 24619407 4 41 theme glycoproteins 826:838 arg1 clearance 707:715 the clearance 703:715 the clearance of glycoproteins such as LH that bear N-linked glycans terminating with β1,4-linked GalNAc-4-SO4, as well as glycoproteins bearing glycans that terminate with Man 703:878 We demonstrate that the ManR mediates the clearance of glycoproteins such as LH that bear N-linked glycans terminating with β1,4-linked GalNAc-4-SO4, as well as glycoproteins bearing glycans that terminate with Man. 24619407 3 42 dep abundant 450:457 arg1 endocytic 483:491 endocytic 483:491 endocytic 483:491 Two highly abundant, carbohydrate-specific, endocytic receptors, the asialoglycoprotein receptor (ASGR) and the mannose receptor (ManR) are expressed in the liver by parenchymal and sinusoidal endothelial cells, respectively. 24619407 3 42 dep abundant 450:457 arg1 carbohydrate-specific 460:480 carbohydrate-specific 460:480 carbohydrate-specific 460:480 Two highly abundant, carbohydrate-specific, endocytic receptors, the asialoglycoprotein receptor (ASGR) and the mannose receptor (ManR) are expressed in the liver by parenchymal and sinusoidal endothelial cells, respectively. 24619407 0 43 theme expression 54:63 arg1 Modulation 0:9 Modulation 0:9 Modulation of mannose and asialoglycoprotein receptor expression 0:63 Modulation of mannose and asialoglycoprotein receptor expression determines glycoprotein hormone half-life at critical points in the reproductive cycle. 24619407 4 44 contain bear 750:753 arg1 LH 742:743 LH 742:743 LH that bear N-linked glycans terminating with β1,4-linked GalNAc-4-SO4 742:812 We demonstrate that the ManR mediates the clearance of glycoproteins such as LH that bear N-linked glycans terminating with β1,4-linked GalNAc-4-SO4, as well as glycoproteins bearing glycans that terminate with Man. 24619407 4 44 contain bear 750:753 arg2 glycans 764:770 N-linked glycans 755:770 N-linked glycans terminating with β1,4-linked GalNAc-4-SO4 755:812 We demonstrate that the ManR mediates the clearance of glycoproteins such as LH that bear N-linked glycans terminating with β1,4-linked GalNAc-4-SO4, as well as glycoproteins bearing glycans that terminate with Man. 24619407 9 45 from time 1405:1408 arg1 expression 1375:1384 reduced expression 1367:1384 reduced expression of the ManR at the time of sexual maturation 1367:1429 Thus, reduced expression of the ManR at the time of sexual maturation will increase the potency of LH in vivo, whereas increased expression during pregnancy will reduce LH potency until progesterone and receptor levels fall prior to parturition. 24619407 5 46 theme pregnancy 1027:1035 arg1 day 1015:1017 day 12.5 1015:1022 day 12.5 of pregnancy 1015:1035 Steady state levels of mRNA encoding the ASGR and the ManR are regulated by progesterone in pregnant mice, reaching maximal levels on day 12.5 of pregnancy. 24619407 7 47 theme maturation 1228:1237 arg1 time 1213:1216 the time 1209:1216 the time of sexual maturation 1209:1237 In contrast, ManR mRNA, but not ASGR mRNA, decreases in male mice at the time of sexual maturation. 24619407 2 48 theme luteinizing 337:347 arg1 LH 358:359 LH 358:359 LH 358:359 We have shown that clearance rates for glycoproteins such as luteinizing hormone (LH) that undergo regulated release into the circulation determine their potency. 24619407 2 48 theme luteinizing 337:347 arg1 hormone 349:355 luteinizing hormone 337:355 luteinizing hormone (LH) that undergo regulated release into the circulation 337:412 We have shown that clearance rates for glycoproteins such as luteinizing hormone (LH) that undergo regulated release into the circulation determine their potency. 24619407 5 49 theme maximal 997:1003 arg1 levels 1005:1010 maximal levels 997:1010 maximal levels 997:1010 Steady state levels of mRNA encoding the ASGR and the ManR are regulated by progesterone in pregnant mice, reaching maximal levels on day 12.5 of pregnancy. 24619407 1 50 gly glycoproteins 171:183 arg1 glycoproteins 171:183 glycoproteins 171:183 glycoproteins 171:183 The rate at which glycoproteins are cleared from the circulation has a critical impact on their biologic activity in vivo. 24619407 3 51 theme parenchymal 605:615 arg1 cells 644:648 parenchymal and sinusoidal endothelial cells 605:648 parenchymal and sinusoidal endothelial cells 605:648 Two highly abundant, carbohydrate-specific, endocytic receptors, the asialoglycoprotein receptor (ASGR) and the mannose receptor (ManR) are expressed in the liver by parenchymal and sinusoidal endothelial cells, respectively. 24619407 0 52 gly asialoglycoprotein 26:43 arg1 asialoglycoprotein 26:43 mannose and asialoglycoprotein receptor expression 14:63 asialoglycoprotein 26:43 Modulation of mannose and asialoglycoprotein receptor expression determines glycoprotein hormone half-life at critical points in the reproductive cycle. 24619407 9 53 theme LH 1460:1461 arg1 potency 1449:1455 the potency 1445:1455 the potency of LH 1445:1461 Thus, reduced expression of the ManR at the time of sexual maturation will increase the potency of LH in vivo, whereas increased expression during pregnancy will reduce LH potency until progesterone and receptor levels fall prior to parturition. 24619407 4 54 link N-linked 755:762 arg1 glycans 764:770 N-linked glycans 755:770 N-linked glycans terminating with β1,4-linked GalNAc-4-SO4 755:812 We demonstrate that the ManR mediates the clearance of glycoproteins such as LH that bear N-linked glycans terminating with β1,4-linked GalNAc-4-SO4, as well as glycoproteins bearing glycans that terminate with Man. 24619407 5 55 theme pregnant 973:980 arg1 mice 982:985 pregnant mice 973:985 pregnant mice 973:985 Steady state levels of mRNA encoding the ASGR and the ManR are regulated by progesterone in pregnant mice, reaching maximal levels on day 12.5 of pregnancy. 24619407 1 56 contain has 218:220 arg2 impact 233:238 a critical impact 222:238 a critical impact 222:238 The rate at which glycoproteins are cleared from the circulation has a critical impact on their biologic activity in vivo. 24619407 1 56 contain has 218:220 arg1 rate 157:160 The rate 153:160 The rate at which glycoproteins are cleared from the circulation 153:216 The rate at which glycoproteins are cleared from the circulation has a critical impact on their biologic activity in vivo. 24619407 4 57 theme N-linked 755:762 arg1 glycans 764:770 N-linked glycans 755:770 N-linked glycans terminating with β1,4-linked GalNAc-4-SO4 755:812 We demonstrate that the ManR mediates the clearance of glycoproteins such as LH that bear N-linked glycans terminating with β1,4-linked GalNAc-4-SO4, as well as glycoproteins bearing glycans that terminate with Man. 24619407 7 58 theme sexual 1221:1226 arg1 maturation 1228:1237 sexual maturation 1221:1237 sexual maturation 1221:1237 In contrast, ManR mRNA, but not ASGR mRNA, decreases in male mice at the time of sexual maturation. 24619407 8 59 theme ASGR 1272:1275 arg1 expression 1277:1286 ASGR expression 1272:1286 ASGR expression 1272:1286 We show that levels of ManR and ASGR expression control the clearance rate for glycoproteins bearing recognized glycans. 24619407 4 60 theme glycoproteins 720:732 arg1 clearance 707:715 the clearance 703:715 the clearance of glycoproteins such as LH that bear N-linked glycans terminating with β1,4-linked GalNAc-4-SO4, as well as glycoproteins bearing glycans that terminate with Man 703:878 We demonstrate that the ManR mediates the clearance of glycoproteins such as LH that bear N-linked glycans terminating with β1,4-linked GalNAc-4-SO4, as well as glycoproteins bearing glycans that terminate with Man. 24619407 0 61 theme hormone 89:95 arg1 half-life 97:105 glycoprotein hormone half-life 76:105 glycoprotein hormone half-life 76:105 Modulation of mannose and asialoglycoprotein receptor expression determines glycoprotein hormone half-life at critical points in the reproductive cycle. 24619407 9 62 theme maturation 1420:1429 arg1 time 1405:1408 the time 1401:1408 the time of sexual maturation 1401:1429 Thus, reduced expression of the ManR at the time of sexual maturation will increase the potency of LH in vivo, whereas increased expression during pregnancy will reduce LH potency until progesterone and receptor levels fall prior to parturition. 24619407 5 63 theme state 888:892 arg1 levels 894:899 Steady state levels 881:899 Steady state levels of mRNA encoding the ASGR and the ManR 881:938 Steady state levels of mRNA encoding the ASGR and the ManR are regulated by progesterone in pregnant mice, reaching maximal levels on day 12.5 of pregnancy. 24619407 7 64 theme male 1196:1199 arg1 mice 1201:1204 male mice 1196:1204 male mice 1196:1204 In contrast, ManR mRNA, but not ASGR mRNA, decreases in male mice at the time of sexual maturation. 24619407 2 65 gly glycoproteins 315:327 arg1 hormone 349:355 luteinizing hormone 337:355 luteinizing hormone (LH) that undergo regulated release into the circulation 337:412 We have shown that clearance rates for glycoproteins such as luteinizing hormone (LH) that undergo regulated release into the circulation determine their potency. 24619407 2 65 gly glycoproteins 315:327 arg1 glycoproteins 315:327 glycoproteins 315:327 glycoproteins such as luteinizing hormone (LH) that undergo regulated release into the circulation 315:412 We have shown that clearance rates for glycoproteins such as luteinizing hormone (LH) that undergo regulated release into the circulation determine their potency. 24619407 6 66 theme mice 1134:1137 arg1 livers 1115:1120 the livers 1111:1120 the livers of pregnant mice 1111:1137 Protein expression and glycan-specific binding activity also increase in the livers of pregnant mice. 24619407 4 67 gly glycoproteins 826:838 arg1 LH 742:743 LH 742:743 LH that bear N-linked glycans terminating with β1,4-linked GalNAc-4-SO4 742:812 We demonstrate that the ManR mediates the clearance of glycoproteins such as LH that bear N-linked glycans terminating with β1,4-linked GalNAc-4-SO4, as well as glycoproteins bearing glycans that terminate with Man. 24619407 4 67 gly glycoproteins 826:838 arg1 glycoproteins 826:838 glycoproteins 826:838 glycoproteins bearing glycans that terminate with Man 826:878 We demonstrate that the ManR mediates the clearance of glycoproteins such as LH that bear N-linked glycans terminating with β1,4-linked GalNAc-4-SO4, as well as glycoproteins bearing glycans that terminate with Man. 24619407 9 68 theme increased 1480:1488 arg1 expression 1490:1499 increased expression 1480:1499 increased expression during pregnancy 1480:1516 Thus, reduced expression of the ManR at the time of sexual maturation will increase the potency of LH in vivo, whereas increased expression during pregnancy will reduce LH potency until progesterone and receptor levels fall prior to parturition. 24619407 7 69 theme ManR 1153:1156 arg1 mRNA 1158:1161 ManR mRNA 1153:1161 ManR mRNA 1153:1161 In contrast, ManR mRNA, but not ASGR mRNA, decreases in male mice at the time of sexual maturation. 24619407 1 70 theme biologic 249:256 arg1 activity 258:265 their biologic activity 243:265 their biologic activity in vivo 243:273 The rate at which glycoproteins are cleared from the circulation has a critical impact on their biologic activity in vivo. 28801661 3 0 from condition 540:548 arg1 occupancy 506:514 site occupancy 501:514 site occupancy of modifications in one condition 501:548 In this manuscript, we distinguish three statistical goals for therapeutic protein characterization: (1) estimation of site occupancy of modifications in one condition, (2) detection of differential site occupancy between conditions, and (3) estimation of combined site occupancy across multiple modification sites. 28801661 7 1 theme appropriate 1422:1432 arg1 modeling 1446:1453 appropriate statistical modeling 1422:1453 appropriate statistical modeling 1422:1453 The results demonstrated the importance of replicated studies of protein characterization, and of appropriate statistical modeling, for reproducible, accurate and efficient site occupancy estimation and differential analysis. 28801661 7 2 theme site 1497:1500 arg1 estimation 1512:1521 reproducible, accurate and efficient site occupancy estimation 1460:1521 reproducible, accurate and efficient site occupancy estimation 1460:1521 The results demonstrated the importance of replicated studies of protein characterization, and of appropriate statistical modeling, for reproducible, accurate and efficient site occupancy estimation and differential analysis. 28801661 1 3 theme mass 117:120 arg1 spectrometry 122:133 liquid chromatography-tandem mass spectrometry 88:133 liquid chromatography-tandem mass spectrometry (LC-MS/MS) 88:144 Peptide mapping with liquid chromatography-tandem mass spectrometry (LC-MS/MS) is an important analytical method for characterization of post-translational and chemical modifications in therapeutic proteins. 28801661 1 3 theme mass 117:120 arg1 LC-MS/MS 136:143 LC-MS/MS 136:143 LC-MS/MS 136:143 Peptide mapping with liquid chromatography-tandem mass spectrometry (LC-MS/MS) is an important analytical method for characterization of post-translational and chemical modifications in therapeutic proteins. 28801661 3 4 theme differential 568:579 arg1 occupancy 586:594 differential site occupancy 568:594 differential site occupancy 568:594 In this manuscript, we distinguish three statistical goals for therapeutic protein characterization: (1) estimation of site occupancy of modifications in one condition, (2) detection of differential site occupancy between conditions, and (3) estimation of combined site occupancy across multiple modification sites. 28801661 6 5 with simulation 1105:1114 arg1 measurements 1267:1278 orthogonal experimental measurements 1243:1278 orthogonal experimental measurements of N-linked glycoforms 1243:1301 The performance was compared to a 'naïve' data analysis approach, by using computer simulation, evaluation of differential site occupancy in positive and negative controls, and comparisons of estimated site occupancy with orthogonal experimental measurements of N-linked glycoforms and total oxidation. 28801661 6 5 with simulation 1105:1114 arg1 oxidation 1313:1321 total oxidation 1307:1321 total oxidation 1307:1321 The performance was compared to a 'naïve' data analysis approach, by using computer simulation, evaluation of differential site occupancy in positive and negative controls, and comparisons of estimated site occupancy with orthogonal experimental measurements of N-linked glycoforms and total oxidation. 28801661 1 6 theme post-translational 204:221 arg1 modifications 236:248 post-translational and chemical modifications 204:248 modifications 236:248 Peptide mapping with liquid chromatography-tandem mass spectrometry (LC-MS/MS) is an important analytical method for characterization of post-translational and chemical modifications in therapeutic proteins. 28801661 6 7 with evaluation 1117:1126 arg1 measurements 1267:1278 orthogonal experimental measurements 1243:1278 orthogonal experimental measurements of N-linked glycoforms 1243:1301 The performance was compared to a 'naïve' data analysis approach, by using computer simulation, evaluation of differential site occupancy in positive and negative controls, and comparisons of estimated site occupancy with orthogonal experimental measurements of N-linked glycoforms and total oxidation. 28801661 6 7 with evaluation 1117:1126 arg1 oxidation 1313:1321 total oxidation 1307:1321 total oxidation 1307:1321 The performance was compared to a 'naïve' data analysis approach, by using computer simulation, evaluation of differential site occupancy in positive and negative controls, and comparisons of estimated site occupancy with orthogonal experimental measurements of N-linked glycoforms and total oxidation. 28801661 4 8 theme LC-MS/MS 876:883 arg1 data 885:888 LC-MS/MS data 876:888 LC-MS/MS data 876:888 We propose an approach, which addresses these goals in terms of summarizing the quantitative information from the mass spectra, statistical modeling, and model-based analysis of LC-MS/MS data. 28801661 6 9 theme N-linked 1283:1290 arg1 glycoforms 1292:1301 N-linked glycoforms 1283:1301 N-linked glycoforms 1283:1301 The performance was compared to a 'naïve' data analysis approach, by using computer simulation, evaluation of differential site occupancy in positive and negative controls, and comparisons of estimated site occupancy with orthogonal experimental measurements of N-linked glycoforms and total oxidation. 28801661 1 10 theme chemical 227:234 arg1 modifications 236:248 post-translational and chemical modifications 204:248 modifications 236:248 Peptide mapping with liquid chromatography-tandem mass spectrometry (LC-MS/MS) is an important analytical method for characterization of post-translational and chemical modifications in therapeutic proteins. 28801661 7 11 theme statistical 1434:1444 arg1 modeling 1446:1453 appropriate statistical modeling 1422:1453 appropriate statistical modeling 1422:1453 The results demonstrated the importance of replicated studies of protein characterization, and of appropriate statistical modeling, for reproducible, accurate and efficient site occupancy estimation and differential analysis. 28801661 6 12 link N-linked 1283:1290 arg1 glycoforms 1292:1301 N-linked glycoforms 1283:1301 N-linked glycoforms 1283:1301 The performance was compared to a 'naïve' data analysis approach, by using computer simulation, evaluation of differential site occupancy in positive and negative controls, and comparisons of estimated site occupancy with orthogonal experimental measurements of N-linked glycoforms and total oxidation. 28801661 3 13 theme occupancy 586:594 arg1 estimation 624:633 (3) estimation 620:633 (3) estimation of combined site occupancy across multiple modification sites 620:695 In this manuscript, we distinguish three statistical goals for therapeutic protein characterization: (1) estimation of site occupancy of modifications in one condition, (2) detection of differential site occupancy between conditions, and (3) estimation of combined site occupancy across multiple modification sites. 28801661 3 13 theme occupancy 586:594 arg1 goals 435:439 three statistical goals 417:439 three statistical goals for therapeutic protein characterization: (1) estimation of site occupancy of modifications in one condition, (2) detection of differential site occupancy between conditions, and (3) estimation of combined site occupancy across multiple modification sites 417:695 In this manuscript, we distinguish three statistical goals for therapeutic protein characterization: (1) estimation of site occupancy of modifications in one condition, (2) detection of differential site occupancy between conditions, and (3) estimation of combined site occupancy across multiple modification sites. 28801661 3 13 theme occupancy 586:594 arg1 detection 555:563 (2) detection 551:563 (2) detection of differential site occupancy between conditions 551:613 In this manuscript, we distinguish three statistical goals for therapeutic protein characterization: (1) estimation of site occupancy of modifications in one condition, (2) detection of differential site occupancy between conditions, and (3) estimation of combined site occupancy across multiple modification sites. 28801661 3 13 theme occupancy 586:594 arg1 estimation 487:496 (1) estimation 483:496 (1) estimation of site occupancy of modifications in one condition 483:548 In this manuscript, we distinguish three statistical goals for therapeutic protein characterization: (1) estimation of site occupancy of modifications in one condition, (2) detection of differential site occupancy between conditions, and (3) estimation of combined site occupancy across multiple modification sites. 28801661 3 14 dep estimation 624:633 arg1 3 621:621 3 621:621 3 621:621 In this manuscript, we distinguish three statistical goals for therapeutic protein characterization: (1) estimation of site occupancy of modifications in one condition, (2) detection of differential site occupancy between conditions, and (3) estimation of combined site occupancy across multiple modification sites. 28801661 6 15 with comparisons 1198:1208 arg1 measurements 1267:1278 orthogonal experimental measurements 1243:1278 orthogonal experimental measurements of N-linked glycoforms 1243:1301 The performance was compared to a 'naïve' data analysis approach, by using computer simulation, evaluation of differential site occupancy in positive and negative controls, and comparisons of estimated site occupancy with orthogonal experimental measurements of N-linked glycoforms and total oxidation. 28801661 6 15 with comparisons 1198:1208 arg1 oxidation 1313:1321 total oxidation 1307:1321 total oxidation 1307:1321 The performance was compared to a 'naïve' data analysis approach, by using computer simulation, evaluation of differential site occupancy in positive and negative controls, and comparisons of estimated site occupancy with orthogonal experimental measurements of N-linked glycoforms and total oxidation. 28801661 7 16 theme modeling 1446:1453 arg1 importance 1353:1362 the importance 1349:1362 the importance of replicated studies of protein characterization, and of appropriate statistical modeling 1349:1453 The results demonstrated the importance of replicated studies of protein characterization, and of appropriate statistical modeling, for reproducible, accurate and efficient site occupancy estimation and differential analysis. 28801661 1 17 with mapping 75:81 arg1 spectrometry 122:133 liquid chromatography-tandem mass spectrometry 88:133 liquid chromatography-tandem mass spectrometry (LC-MS/MS) 88:144 Peptide mapping with liquid chromatography-tandem mass spectrometry (LC-MS/MS) is an important analytical method for characterization of post-translational and chemical modifications in therapeutic proteins. 28801661 1 17 with mapping 75:81 arg1 LC-MS/MS 136:143 LC-MS/MS 136:143 LC-MS/MS 136:143 Peptide mapping with liquid chromatography-tandem mass spectrometry (LC-MS/MS) is an important analytical method for characterization of post-translational and chemical modifications in therapeutic proteins. 28801661 6 18 theme experimental 1254:1265 arg1 measurements 1267:1278 orthogonal experimental measurements 1243:1278 orthogonal experimental measurements of N-linked glycoforms 1243:1301 The performance was compared to a 'naïve' data analysis approach, by using computer simulation, evaluation of differential site occupancy in positive and negative controls, and comparisons of estimated site occupancy with orthogonal experimental measurements of N-linked glycoforms and total oxidation. 28801661 1 19 from modifications 236:248 arg1 proteins 265:272 therapeutic proteins 253:272 therapeutic proteins 253:272 Peptide mapping with liquid chromatography-tandem mass spectrometry (LC-MS/MS) is an important analytical method for characterization of post-translational and chemical modifications in therapeutic proteins. 28801661 3 20 dep detection 555:563 arg1 2 552:552 2 552:552 2 552:552 In this manuscript, we distinguish three statistical goals for therapeutic protein characterization: (1) estimation of site occupancy of modifications in one condition, (2) detection of differential site occupancy between conditions, and (3) estimation of combined site occupancy across multiple modification sites. 28801661 2 21 from consensus 321:329 arg1 analysis 350:357 the statistical analysis 334:357 the statistical analysis of the resulting data 334:379 Despite its importance, there is currently no consensus on the statistical analysis of the resulting data. 28801661 3 22 theme combined 638:645 arg1 occupancy 652:660 combined site occupancy 638:660 combined site occupancy 638:660 In this manuscript, we distinguish three statistical goals for therapeutic protein characterization: (1) estimation of site occupancy of modifications in one condition, (2) detection of differential site occupancy between conditions, and (3) estimation of combined site occupancy across multiple modification sites. 28801661 1 23 theme important 152:160 arg1 method 173:178 an important analytical method 149:178 an important analytical method for characterization of post-translational and chemical modifications in therapeutic proteins 149:272 Peptide mapping with liquid chromatography-tandem mass spectrometry (LC-MS/MS) is an important analytical method for characterization of post-translational and chemical modifications in therapeutic proteins. 28801661 1 23 theme important 152:160 arg1 mapping 75:81 Peptide mapping 67:81 Peptide mapping with liquid chromatography-tandem mass spectrometry (LC-MS/MS) 67:144 Peptide mapping with liquid chromatography-tandem mass spectrometry (LC-MS/MS) is an important analytical method for characterization of post-translational and chemical modifications in therapeutic proteins. 28801661 6 24 theme site 1223:1226 arg1 occupancy 1228:1236 estimated site occupancy 1213:1236 estimated site occupancy 1213:1236 The performance was compared to a 'naïve' data analysis approach, by using computer simulation, evaluation of differential site occupancy in positive and negative controls, and comparisons of estimated site occupancy with orthogonal experimental measurements of N-linked glycoforms and total oxidation. 28801661 4 25 theme quantitative 778:789 arg1 information 791:801 the quantitative information 774:801 the quantitative information from the mass spectra 774:823 We propose an approach, which addresses these goals in terms of summarizing the quantitative information from the mass spectra, statistical modeling, and model-based analysis of LC-MS/MS data. 28801661 5 26 theme antibody 998:1005 arg1 intermediate 1007:1018 its monoclonal antibody intermediate 983:1018 its monoclonal antibody intermediate 983:1018 We illustrate the approach using an LC-MS/MS experiment from an antibody-drug conjugate and its monoclonal antibody intermediate. 28801661 1 27 theme chromatography-tandem 95:115 arg1 spectrometry 122:133 liquid chromatography-tandem mass spectrometry 88:133 liquid chromatography-tandem mass spectrometry (LC-MS/MS) 88:144 Peptide mapping with liquid chromatography-tandem mass spectrometry (LC-MS/MS) is an important analytical method for characterization of post-translational and chemical modifications in therapeutic proteins. 28801661 1 27 theme chromatography-tandem 95:115 arg1 LC-MS/MS 136:143 LC-MS/MS 136:143 LC-MS/MS 136:143 Peptide mapping with liquid chromatography-tandem mass spectrometry (LC-MS/MS) is an important analytical method for characterization of post-translational and chemical modifications in therapeutic proteins. 28801661 7 28 theme protein 1389:1395 arg1 characterization 1397:1412 protein characterization 1389:1412 protein characterization 1389:1412 The results demonstrated the importance of replicated studies of protein characterization, and of appropriate statistical modeling, for reproducible, accurate and efficient site occupancy estimation and differential analysis. 28801661 3 29 theme statistical 423:433 arg1 estimation 624:633 (3) estimation 620:633 (3) estimation of combined site occupancy across multiple modification sites 620:695 In this manuscript, we distinguish three statistical goals for therapeutic protein characterization: (1) estimation of site occupancy of modifications in one condition, (2) detection of differential site occupancy between conditions, and (3) estimation of combined site occupancy across multiple modification sites. 28801661 3 29 theme statistical 423:433 arg1 goals 435:439 three statistical goals 417:439 three statistical goals for therapeutic protein characterization: (1) estimation of site occupancy of modifications in one condition, (2) detection of differential site occupancy between conditions, and (3) estimation of combined site occupancy across multiple modification sites 417:695 In this manuscript, we distinguish three statistical goals for therapeutic protein characterization: (1) estimation of site occupancy of modifications in one condition, (2) detection of differential site occupancy between conditions, and (3) estimation of combined site occupancy across multiple modification sites. 28801661 3 29 theme statistical 423:433 arg1 detection 555:563 (2) detection 551:563 (2) detection of differential site occupancy between conditions 551:613 In this manuscript, we distinguish three statistical goals for therapeutic protein characterization: (1) estimation of site occupancy of modifications in one condition, (2) detection of differential site occupancy between conditions, and (3) estimation of combined site occupancy across multiple modification sites. 28801661 3 29 theme statistical 423:433 arg1 estimation 487:496 (1) estimation 483:496 (1) estimation of site occupancy of modifications in one condition 483:548 In this manuscript, we distinguish three statistical goals for therapeutic protein characterization: (1) estimation of site occupancy of modifications in one condition, (2) detection of differential site occupancy between conditions, and (3) estimation of combined site occupancy across multiple modification sites. 28801661 6 30 from comparisons 1198:1208 arg1 controls 1184:1191 positive and negative controls 1162:1191 positive and negative controls 1162:1191 The performance was compared to a 'naïve' data analysis approach, by using computer simulation, evaluation of differential site occupancy in positive and negative controls, and comparisons of estimated site occupancy with orthogonal experimental measurements of N-linked glycoforms and total oxidation. 28801661 0 31 theme Statistical 0:10 arg1 characterization 12:27 Statistical characterization 0:27 Statistical characterization of therapeutic protein modifications. 0:65 Statistical characterization of therapeutic protein modifications. 28801661 7 32 theme studies 1378:1384 arg1 importance 1353:1362 the importance 1349:1362 the importance of replicated studies of protein characterization, and of appropriate statistical modeling 1349:1453 The results demonstrated the importance of replicated studies of protein characterization, and of appropriate statistical modeling, for reproducible, accurate and efficient site occupancy estimation and differential analysis. 28801661 7 33 theme characterization 1397:1412 arg1 importance 1353:1362 the importance 1349:1362 the importance of replicated studies of protein characterization, and of appropriate statistical modeling 1349:1453 The results demonstrated the importance of replicated studies of protein characterization, and of appropriate statistical modeling, for reproducible, accurate and efficient site occupancy estimation and differential analysis. 28801661 3 34 theme site 501:504 arg1 occupancy 506:514 site occupancy 501:514 site occupancy of modifications in one condition 501:548 In this manuscript, we distinguish three statistical goals for therapeutic protein characterization: (1) estimation of site occupancy of modifications in one condition, (2) detection of differential site occupancy between conditions, and (3) estimation of combined site occupancy across multiple modification sites. 28801661 6 35 theme analysis 1068:1075 arg1 approach 1077:1084 a 'naïve' data analysis approach 1053:1084 a 'naïve' data analysis approach 1053:1084 The performance was compared to a 'naïve' data analysis approach, by using computer simulation, evaluation of differential site occupancy in positive and negative controls, and comparisons of estimated site occupancy with orthogonal experimental measurements of N-linked glycoforms and total oxidation. 28801661 3 36 theme protein 457:463 arg1 characterization 465:480 therapeutic protein characterization 445:480 therapeutic protein characterization 445:480 In this manuscript, we distinguish three statistical goals for therapeutic protein characterization: (1) estimation of site occupancy of modifications in one condition, (2) detection of differential site occupancy between conditions, and (3) estimation of combined site occupancy across multiple modification sites. 28801661 3 37 theme multiple 669:676 arg1 sites 691:695 multiple modification sites 669:695 multiple modification sites 669:695 In this manuscript, we distinguish three statistical goals for therapeutic protein characterization: (1) estimation of site occupancy of modifications in one condition, (2) detection of differential site occupancy between conditions, and (3) estimation of combined site occupancy across multiple modification sites. 28801661 3 38 gly occupancy 506:514 arg2 site 501:504 site occupancy 501:514 site occupancy of modifications in one condition 501:548 In this manuscript, we distinguish three statistical goals for therapeutic protein characterization: (1) estimation of site occupancy of modifications in one condition, (2) detection of differential site occupancy between conditions, and (3) estimation of combined site occupancy across multiple modification sites. 28801661 3 38 gly occupancy 506:514 arg1 modifications 519:531 modifications 519:531 modifications in one condition 519:548 In this manuscript, we distinguish three statistical goals for therapeutic protein characterization: (1) estimation of site occupancy of modifications in one condition, (2) detection of differential site occupancy between conditions, and (3) estimation of combined site occupancy across multiple modification sites. 28801661 3 38 gly occupancy 506:514 arg2 modifications 519:531 modifications 519:531 modifications in one condition 519:548 In this manuscript, we distinguish three statistical goals for therapeutic protein characterization: (1) estimation of site occupancy of modifications in one condition, (2) detection of differential site occupancy between conditions, and (3) estimation of combined site occupancy across multiple modification sites. 28801661 0 39 theme protein 44:50 arg1 modifications 52:64 therapeutic protein modifications 32:64 therapeutic protein modifications 32:64 Statistical characterization of therapeutic protein modifications. 28801661 3 40 theme occupancy 652:660 arg1 estimation 624:633 (3) estimation 620:633 (3) estimation of combined site occupancy across multiple modification sites 620:695 In this manuscript, we distinguish three statistical goals for therapeutic protein characterization: (1) estimation of site occupancy of modifications in one condition, (2) detection of differential site occupancy between conditions, and (3) estimation of combined site occupancy across multiple modification sites. 28801661 3 40 theme occupancy 652:660 arg1 goals 435:439 three statistical goals 417:439 three statistical goals for therapeutic protein characterization: (1) estimation of site occupancy of modifications in one condition, (2) detection of differential site occupancy between conditions, and (3) estimation of combined site occupancy across multiple modification sites 417:695 In this manuscript, we distinguish three statistical goals for therapeutic protein characterization: (1) estimation of site occupancy of modifications in one condition, (2) detection of differential site occupancy between conditions, and (3) estimation of combined site occupancy across multiple modification sites. 28801661 3 40 theme occupancy 652:660 arg1 detection 555:563 (2) detection 551:563 (2) detection of differential site occupancy between conditions 551:613 In this manuscript, we distinguish three statistical goals for therapeutic protein characterization: (1) estimation of site occupancy of modifications in one condition, (2) detection of differential site occupancy between conditions, and (3) estimation of combined site occupancy across multiple modification sites. 28801661 3 40 theme occupancy 652:660 arg1 estimation 487:496 (1) estimation 483:496 (1) estimation of site occupancy of modifications in one condition 483:548 In this manuscript, we distinguish three statistical goals for therapeutic protein characterization: (1) estimation of site occupancy of modifications in one condition, (2) detection of differential site occupancy between conditions, and (3) estimation of combined site occupancy across multiple modification sites. 28801661 6 41 theme occupancy 1149:1157 arg1 evaluation 1117:1126 evaluation 1117:1126 evaluation of differential site occupancy in positive and negative controls 1117:1191 The performance was compared to a 'naïve' data analysis approach, by using computer simulation, evaluation of differential site occupancy in positive and negative controls, and comparisons of estimated site occupancy with orthogonal experimental measurements of N-linked glycoforms and total oxidation. 28801661 6 41 theme occupancy 1149:1157 arg1 simulation 1105:1114 computer simulation 1096:1114 computer simulation 1096:1114 The performance was compared to a 'naïve' data analysis approach, by using computer simulation, evaluation of differential site occupancy in positive and negative controls, and comparisons of estimated site occupancy with orthogonal experimental measurements of N-linked glycoforms and total oxidation. 28801661 6 41 theme occupancy 1149:1157 arg1 comparisons 1198:1208 comparisons 1198:1208 comparisons of estimated site occupancy with orthogonal experimental measurements of N-linked glycoforms and total oxidation 1198:1321 The performance was compared to a 'naïve' data analysis approach, by using computer simulation, evaluation of differential site occupancy in positive and negative controls, and comparisons of estimated site occupancy with orthogonal experimental measurements of N-linked glycoforms and total oxidation. 28801661 4 42 theme mass 812:815 arg1 spectra 817:823 the mass spectra 808:823 the mass spectra 808:823 We propose an approach, which addresses these goals in terms of summarizing the quantitative information from the mass spectra, statistical modeling, and model-based analysis of LC-MS/MS data. 28801661 3 43 from occupancy 506:514 arg1 condition 540:548 one condition 536:548 one condition 536:548 In this manuscript, we distinguish three statistical goals for therapeutic protein characterization: (1) estimation of site occupancy of modifications in one condition, (2) detection of differential site occupancy between conditions, and (3) estimation of combined site occupancy across multiple modification sites. 28801661 2 44 theme data 376:379 arg1 analysis 350:357 the statistical analysis 334:357 the statistical analysis of the resulting data 334:379 Despite its importance, there is currently no consensus on the statistical analysis of the resulting data. 28801661 6 45 theme differential 1131:1142 arg1 occupancy 1149:1157 differential site occupancy 1131:1157 differential site occupancy in positive and negative controls 1131:1191 The performance was compared to a 'naïve' data analysis approach, by using computer simulation, evaluation of differential site occupancy in positive and negative controls, and comparisons of estimated site occupancy with orthogonal experimental measurements of N-linked glycoforms and total oxidation. 28801661 6 46 from simulation 1105:1114 arg1 controls 1184:1191 positive and negative controls 1162:1191 positive and negative controls 1162:1191 The performance was compared to a 'naïve' data analysis approach, by using computer simulation, evaluation of differential site occupancy in positive and negative controls, and comparisons of estimated site occupancy with orthogonal experimental measurements of N-linked glycoforms and total oxidation. 28801661 1 47 theme Peptide 67:73 arg1 method 173:178 an important analytical method 149:178 an important analytical method for characterization of post-translational and chemical modifications in therapeutic proteins 149:272 Peptide mapping with liquid chromatography-tandem mass spectrometry (LC-MS/MS) is an important analytical method for characterization of post-translational and chemical modifications in therapeutic proteins. 28801661 1 47 theme Peptide 67:73 arg1 mapping 75:81 Peptide mapping 67:81 Peptide mapping with liquid chromatography-tandem mass spectrometry (LC-MS/MS) 67:144 Peptide mapping with liquid chromatography-tandem mass spectrometry (LC-MS/MS) is an important analytical method for characterization of post-translational and chemical modifications in therapeutic proteins. 28801661 6 48 from evaluation 1117:1126 arg1 controls 1184:1191 positive and negative controls 1162:1191 positive and negative controls 1162:1191 The performance was compared to a 'naïve' data analysis approach, by using computer simulation, evaluation of differential site occupancy in positive and negative controls, and comparisons of estimated site occupancy with orthogonal experimental measurements of N-linked glycoforms and total oxidation. 28801661 4 49 theme data 885:888 arg1 modeling 838:845 statistical modeling 826:845 statistical modeling 826:845 We propose an approach, which addresses these goals in terms of summarizing the quantitative information from the mass spectra, statistical modeling, and model-based analysis of LC-MS/MS data. 28801661 4 49 theme data 885:888 arg1 information 791:801 the quantitative information 774:801 the quantitative information from the mass spectra 774:823 We propose an approach, which addresses these goals in terms of summarizing the quantitative information from the mass spectra, statistical modeling, and model-based analysis of LC-MS/MS data. 28801661 4 49 theme data 885:888 arg1 analysis 864:871 model-based analysis 852:871 model-based analysis of LC-MS/MS data 852:888 We propose an approach, which addresses these goals in terms of summarizing the quantitative information from the mass spectra, statistical modeling, and model-based analysis of LC-MS/MS data. 28801661 7 50 theme differential 1527:1538 arg1 analysis 1540:1547 differential analysis 1527:1547 differential analysis 1527:1547 The results demonstrated the importance of replicated studies of protein characterization, and of appropriate statistical modeling, for reproducible, accurate and efficient site occupancy estimation and differential analysis. 28801661 7 51 theme occupancy 1502:1510 arg1 estimation 1512:1521 reproducible, accurate and efficient site occupancy estimation 1460:1521 reproducible, accurate and efficient site occupancy estimation 1460:1521 The results demonstrated the importance of replicated studies of protein characterization, and of appropriate statistical modeling, for reproducible, accurate and efficient site occupancy estimation and differential analysis. 28801661 6 52 theme total 1307:1311 arg1 oxidation 1313:1321 total oxidation 1307:1321 total oxidation 1307:1321 The performance was compared to a 'naïve' data analysis approach, by using computer simulation, evaluation of differential site occupancy in positive and negative controls, and comparisons of estimated site occupancy with orthogonal experimental measurements of N-linked glycoforms and total oxidation. 28801661 4 53 theme model-based 852:862 arg1 analysis 864:871 model-based analysis 852:871 model-based analysis of LC-MS/MS data 852:888 We propose an approach, which addresses these goals in terms of summarizing the quantitative information from the mass spectra, statistical modeling, and model-based analysis of LC-MS/MS data. 28801661 7 54 theme efficient 1487:1495 arg1 estimation 1512:1521 reproducible, accurate and efficient site occupancy estimation 1460:1521 reproducible, accurate and efficient site occupancy estimation 1460:1521 The results demonstrated the importance of replicated studies of protein characterization, and of appropriate statistical modeling, for reproducible, accurate and efficient site occupancy estimation and differential analysis. 28801661 6 55 theme glycoforms 1292:1301 arg1 measurements 1267:1278 orthogonal experimental measurements 1243:1278 orthogonal experimental measurements of N-linked glycoforms 1243:1301 The performance was compared to a 'naïve' data analysis approach, by using computer simulation, evaluation of differential site occupancy in positive and negative controls, and comparisons of estimated site occupancy with orthogonal experimental measurements of N-linked glycoforms and total oxidation. 28801661 6 55 theme glycoforms 1292:1301 arg1 oxidation 1313:1321 total oxidation 1307:1321 total oxidation 1307:1321 The performance was compared to a 'naïve' data analysis approach, by using computer simulation, evaluation of differential site occupancy in positive and negative controls, and comparisons of estimated site occupancy with orthogonal experimental measurements of N-linked glycoforms and total oxidation. 28801661 3 56 from modifications 519:531 arg1 condition 540:548 one condition 536:548 one condition 536:548 In this manuscript, we distinguish three statistical goals for therapeutic protein characterization: (1) estimation of site occupancy of modifications in one condition, (2) detection of differential site occupancy between conditions, and (3) estimation of combined site occupancy across multiple modification sites. 28801661 6 57 theme negative 1175:1182 arg1 controls 1184:1191 positive and negative controls 1162:1191 positive and negative controls 1162:1191 The performance was compared to a 'naïve' data analysis approach, by using computer simulation, evaluation of differential site occupancy in positive and negative controls, and comparisons of estimated site occupancy with orthogonal experimental measurements of N-linked glycoforms and total oxidation. 28801661 3 58 theme site 581:584 arg1 occupancy 586:594 differential site occupancy 568:594 differential site occupancy 568:594 In this manuscript, we distinguish three statistical goals for therapeutic protein characterization: (1) estimation of site occupancy of modifications in one condition, (2) detection of differential site occupancy between conditions, and (3) estimation of combined site occupancy across multiple modification sites. 28801661 1 59 theme modifications 236:248 arg1 characterization 184:199 characterization 184:199 characterization of post-translational and chemical modifications in therapeutic proteins 184:272 Peptide mapping with liquid chromatography-tandem mass spectrometry (LC-MS/MS) is an important analytical method for characterization of post-translational and chemical modifications in therapeutic proteins. 28801661 7 60 theme accurate 1474:1481 arg1 estimation 1512:1521 reproducible, accurate and efficient site occupancy estimation 1460:1521 reproducible, accurate and efficient site occupancy estimation 1460:1521 The results demonstrated the importance of replicated studies of protein characterization, and of appropriate statistical modeling, for reproducible, accurate and efficient site occupancy estimation and differential analysis. 28801661 6 61 theme positive 1162:1169 arg1 controls 1184:1191 positive and negative controls 1162:1191 positive and negative controls 1162:1191 The performance was compared to a 'naïve' data analysis approach, by using computer simulation, evaluation of differential site occupancy in positive and negative controls, and comparisons of estimated site occupancy with orthogonal experimental measurements of N-linked glycoforms and total oxidation. 28801661 1 62 theme therapeutic 253:263 arg1 proteins 265:272 therapeutic proteins 253:272 therapeutic proteins 253:272 Peptide mapping with liquid chromatography-tandem mass spectrometry (LC-MS/MS) is an important analytical method for characterization of post-translational and chemical modifications in therapeutic proteins. 28801661 1 63 from proteins 265:272 arg1 characterization 184:199 characterization 184:199 characterization of post-translational and chemical modifications in therapeutic proteins 184:272 Peptide mapping with liquid chromatography-tandem mass spectrometry (LC-MS/MS) is an important analytical method for characterization of post-translational and chemical modifications in therapeutic proteins. 28801661 5 64 theme LC-MS/MS 927:934 arg1 experiment 936:945 an LC-MS/MS experiment 924:945 an LC-MS/MS experiment 924:945 We illustrate the approach using an LC-MS/MS experiment from an antibody-drug conjugate and its monoclonal antibody intermediate. 28801661 6 65 theme orthogonal 1243:1252 arg1 measurements 1267:1278 orthogonal experimental measurements 1243:1278 orthogonal experimental measurements of N-linked glycoforms 1243:1301 The performance was compared to a 'naïve' data analysis approach, by using computer simulation, evaluation of differential site occupancy in positive and negative controls, and comparisons of estimated site occupancy with orthogonal experimental measurements of N-linked glycoforms and total oxidation. 28801661 6 66 theme naïve 1056:1060 arg1 approach 1077:1084 a 'naïve' data analysis approach 1053:1084 a 'naïve' data analysis approach 1053:1084 The performance was compared to a 'naïve' data analysis approach, by using computer simulation, evaluation of differential site occupancy in positive and negative controls, and comparisons of estimated site occupancy with orthogonal experimental measurements of N-linked glycoforms and total oxidation. 28801661 6 67 from occupancy 1149:1157 arg1 controls 1184:1191 positive and negative controls 1162:1191 positive and negative controls 1162:1191 The performance was compared to a 'naïve' data analysis approach, by using computer simulation, evaluation of differential site occupancy in positive and negative controls, and comparisons of estimated site occupancy with orthogonal experimental measurements of N-linked glycoforms and total oxidation. 28801661 6 68 theme occupancy 1228:1236 arg1 evaluation 1117:1126 evaluation 1117:1126 evaluation of differential site occupancy in positive and negative controls 1117:1191 The performance was compared to a 'naïve' data analysis approach, by using computer simulation, evaluation of differential site occupancy in positive and negative controls, and comparisons of estimated site occupancy with orthogonal experimental measurements of N-linked glycoforms and total oxidation. 28801661 6 68 theme occupancy 1228:1236 arg1 simulation 1105:1114 computer simulation 1096:1114 computer simulation 1096:1114 The performance was compared to a 'naïve' data analysis approach, by using computer simulation, evaluation of differential site occupancy in positive and negative controls, and comparisons of estimated site occupancy with orthogonal experimental measurements of N-linked glycoforms and total oxidation. 28801661 6 68 theme occupancy 1228:1236 arg1 comparisons 1198:1208 comparisons 1198:1208 comparisons of estimated site occupancy with orthogonal experimental measurements of N-linked glycoforms and total oxidation 1198:1321 The performance was compared to a 'naïve' data analysis approach, by using computer simulation, evaluation of differential site occupancy in positive and negative controls, and comparisons of estimated site occupancy with orthogonal experimental measurements of N-linked glycoforms and total oxidation. 28801661 4 69 from spectra 817:823 arg1 modeling 838:845 statistical modeling 826:845 statistical modeling 826:845 We propose an approach, which addresses these goals in terms of summarizing the quantitative information from the mass spectra, statistical modeling, and model-based analysis of LC-MS/MS data. 28801661 4 69 from spectra 817:823 arg1 information 791:801 the quantitative information 774:801 the quantitative information from the mass spectra 774:823 We propose an approach, which addresses these goals in terms of summarizing the quantitative information from the mass spectra, statistical modeling, and model-based analysis of LC-MS/MS data. 28801661 4 69 from spectra 817:823 arg1 analysis 864:871 model-based analysis 852:871 model-based analysis of LC-MS/MS data 852:888 We propose an approach, which addresses these goals in terms of summarizing the quantitative information from the mass spectra, statistical modeling, and model-based analysis of LC-MS/MS data. 28801661 1 70 theme analytical 162:171 arg1 method 173:178 an important analytical method 149:178 an important analytical method for characterization of post-translational and chemical modifications in therapeutic proteins 149:272 Peptide mapping with liquid chromatography-tandem mass spectrometry (LC-MS/MS) is an important analytical method for characterization of post-translational and chemical modifications in therapeutic proteins. 28801661 1 70 theme analytical 162:171 arg1 mapping 75:81 Peptide mapping 67:81 Peptide mapping with liquid chromatography-tandem mass spectrometry (LC-MS/MS) 67:144 Peptide mapping with liquid chromatography-tandem mass spectrometry (LC-MS/MS) is an important analytical method for characterization of post-translational and chemical modifications in therapeutic proteins. 28801661 6 71 theme estimated 1213:1221 arg1 occupancy 1228:1236 estimated site occupancy 1213:1236 estimated site occupancy 1213:1236 The performance was compared to a 'naïve' data analysis approach, by using computer simulation, evaluation of differential site occupancy in positive and negative controls, and comparisons of estimated site occupancy with orthogonal experimental measurements of N-linked glycoforms and total oxidation. 28801661 1 72 from characterization 184:199 arg1 proteins 265:272 therapeutic proteins 253:272 therapeutic proteins 253:272 Peptide mapping with liquid chromatography-tandem mass spectrometry (LC-MS/MS) is an important analytical method for characterization of post-translational and chemical modifications in therapeutic proteins. 28801661 5 73 theme monoclonal 987:996 arg1 antibody 998:1005 its monoclonal antibody 983:1005 its monoclonal antibody intermediate 983:1018 We illustrate the approach using an LC-MS/MS experiment from an antibody-drug conjugate and its monoclonal antibody intermediate. 28801661 2 74 theme statistical 338:348 arg1 analysis 350:357 the statistical analysis 334:357 the statistical analysis of the resulting data 334:379 Despite its importance, there is currently no consensus on the statistical analysis of the resulting data. 28801661 3 75 dep goals 435:439 arg1 estimation 624:633 (3) estimation 620:633 (3) estimation of combined site occupancy across multiple modification sites 620:695 In this manuscript, we distinguish three statistical goals for therapeutic protein characterization: (1) estimation of site occupancy of modifications in one condition, (2) detection of differential site occupancy between conditions, and (3) estimation of combined site occupancy across multiple modification sites. 28801661 3 75 dep goals 435:439 arg1 goals 435:439 three statistical goals 417:439 three statistical goals for therapeutic protein characterization: (1) estimation of site occupancy of modifications in one condition, (2) detection of differential site occupancy between conditions, and (3) estimation of combined site occupancy across multiple modification sites 417:695 In this manuscript, we distinguish three statistical goals for therapeutic protein characterization: (1) estimation of site occupancy of modifications in one condition, (2) detection of differential site occupancy between conditions, and (3) estimation of combined site occupancy across multiple modification sites. 28801661 3 75 dep goals 435:439 arg1 detection 555:563 (2) detection 551:563 (2) detection of differential site occupancy between conditions 551:613 In this manuscript, we distinguish three statistical goals for therapeutic protein characterization: (1) estimation of site occupancy of modifications in one condition, (2) detection of differential site occupancy between conditions, and (3) estimation of combined site occupancy across multiple modification sites. 28801661 3 75 dep goals 435:439 arg1 estimation 487:496 (1) estimation 483:496 (1) estimation of site occupancy of modifications in one condition 483:548 In this manuscript, we distinguish three statistical goals for therapeutic protein characterization: (1) estimation of site occupancy of modifications in one condition, (2) detection of differential site occupancy between conditions, and (3) estimation of combined site occupancy across multiple modification sites. 28801661 3 76 theme modifications 519:531 arg1 occupancy 506:514 site occupancy 501:514 site occupancy of modifications in one condition 501:548 In this manuscript, we distinguish three statistical goals for therapeutic protein characterization: (1) estimation of site occupancy of modifications in one condition, (2) detection of differential site occupancy between conditions, and (3) estimation of combined site occupancy across multiple modification sites. 28801661 1 77 theme liquid 88:93 arg1 spectrometry 122:133 liquid chromatography-tandem mass spectrometry 88:133 liquid chromatography-tandem mass spectrometry (LC-MS/MS) 88:144 Peptide mapping with liquid chromatography-tandem mass spectrometry (LC-MS/MS) is an important analytical method for characterization of post-translational and chemical modifications in therapeutic proteins. 28801661 1 77 theme liquid 88:93 arg1 LC-MS/MS 136:143 LC-MS/MS 136:143 LC-MS/MS 136:143 Peptide mapping with liquid chromatography-tandem mass spectrometry (LC-MS/MS) is an important analytical method for characterization of post-translational and chemical modifications in therapeutic proteins. 28801661 6 78 theme computer 1096:1103 arg1 simulation 1105:1114 computer simulation 1096:1114 computer simulation 1096:1114 The performance was compared to a 'naïve' data analysis approach, by using computer simulation, evaluation of differential site occupancy in positive and negative controls, and comparisons of estimated site occupancy with orthogonal experimental measurements of N-linked glycoforms and total oxidation. 28801661 5 79 theme antibody-drug 955:967 arg1 conjugate 969:977 an antibody-drug conjugate 952:977 an antibody-drug conjugate 952:977 We illustrate the approach using an LC-MS/MS experiment from an antibody-drug conjugate and its monoclonal antibody intermediate. 28801661 7 80 theme replicated 1367:1376 arg1 studies 1378:1384 replicated studies 1367:1384 replicated studies 1367:1384 The results demonstrated the importance of replicated studies of protein characterization, and of appropriate statistical modeling, for reproducible, accurate and efficient site occupancy estimation and differential analysis. 28801661 0 81 theme therapeutic 32:42 arg1 modifications 52:64 therapeutic protein modifications 32:64 therapeutic protein modifications 32:64 Statistical characterization of therapeutic protein modifications. 28801661 6 82 from controls 1184:1191 arg1 evaluation 1117:1126 evaluation 1117:1126 evaluation of differential site occupancy in positive and negative controls 1117:1191 The performance was compared to a 'naïve' data analysis approach, by using computer simulation, evaluation of differential site occupancy in positive and negative controls, and comparisons of estimated site occupancy with orthogonal experimental measurements of N-linked glycoforms and total oxidation. 28801661 6 82 from controls 1184:1191 arg1 simulation 1105:1114 computer simulation 1096:1114 computer simulation 1096:1114 The performance was compared to a 'naïve' data analysis approach, by using computer simulation, evaluation of differential site occupancy in positive and negative controls, and comparisons of estimated site occupancy with orthogonal experimental measurements of N-linked glycoforms and total oxidation. 28801661 6 82 from controls 1184:1191 arg1 comparisons 1198:1208 comparisons 1198:1208 comparisons of estimated site occupancy with orthogonal experimental measurements of N-linked glycoforms and total oxidation 1198:1321 The performance was compared to a 'naïve' data analysis approach, by using computer simulation, evaluation of differential site occupancy in positive and negative controls, and comparisons of estimated site occupancy with orthogonal experimental measurements of N-linked glycoforms and total oxidation. 28801661 3 83 theme occupancy 506:514 arg1 estimation 624:633 (3) estimation 620:633 (3) estimation of combined site occupancy across multiple modification sites 620:695 In this manuscript, we distinguish three statistical goals for therapeutic protein characterization: (1) estimation of site occupancy of modifications in one condition, (2) detection of differential site occupancy between conditions, and (3) estimation of combined site occupancy across multiple modification sites. 28801661 3 83 theme occupancy 506:514 arg1 goals 435:439 three statistical goals 417:439 three statistical goals for therapeutic protein characterization: (1) estimation of site occupancy of modifications in one condition, (2) detection of differential site occupancy between conditions, and (3) estimation of combined site occupancy across multiple modification sites 417:695 In this manuscript, we distinguish three statistical goals for therapeutic protein characterization: (1) estimation of site occupancy of modifications in one condition, (2) detection of differential site occupancy between conditions, and (3) estimation of combined site occupancy across multiple modification sites. 28801661 3 83 theme occupancy 506:514 arg1 detection 555:563 (2) detection 551:563 (2) detection of differential site occupancy between conditions 551:613 In this manuscript, we distinguish three statistical goals for therapeutic protein characterization: (1) estimation of site occupancy of modifications in one condition, (2) detection of differential site occupancy between conditions, and (3) estimation of combined site occupancy across multiple modification sites. 28801661 3 83 theme occupancy 506:514 arg1 estimation 487:496 (1) estimation 483:496 (1) estimation of site occupancy of modifications in one condition 483:548 In this manuscript, we distinguish three statistical goals for therapeutic protein characterization: (1) estimation of site occupancy of modifications in one condition, (2) detection of differential site occupancy between conditions, and (3) estimation of combined site occupancy across multiple modification sites. 28801661 0 84 theme modifications 52:64 arg1 characterization 12:27 Statistical characterization 0:27 Statistical characterization of therapeutic protein modifications. 0:65 Statistical characterization of therapeutic protein modifications. 28801661 6 85 theme data 1063:1066 arg1 approach 1077:1084 a 'naïve' data analysis approach 1053:1084 a 'naïve' data analysis approach 1053:1084 The performance was compared to a 'naïve' data analysis approach, by using computer simulation, evaluation of differential site occupancy in positive and negative controls, and comparisons of estimated site occupancy with orthogonal experimental measurements of N-linked glycoforms and total oxidation. 28801661 3 86 theme site 647:650 arg1 occupancy 652:660 combined site occupancy 638:660 combined site occupancy 638:660 In this manuscript, we distinguish three statistical goals for therapeutic protein characterization: (1) estimation of site occupancy of modifications in one condition, (2) detection of differential site occupancy between conditions, and (3) estimation of combined site occupancy across multiple modification sites. 28801661 4 87 theme statistical 826:836 arg1 modeling 838:845 statistical modeling 826:845 statistical modeling 826:845 We propose an approach, which addresses these goals in terms of summarizing the quantitative information from the mass spectra, statistical modeling, and model-based analysis of LC-MS/MS data. 28801661 3 88 theme therapeutic 445:455 arg1 characterization 465:480 therapeutic protein characterization 445:480 therapeutic protein characterization 445:480 In this manuscript, we distinguish three statistical goals for therapeutic protein characterization: (1) estimation of site occupancy of modifications in one condition, (2) detection of differential site occupancy between conditions, and (3) estimation of combined site occupancy across multiple modification sites. 28801661 3 89 dep estimation 487:496 arg1 1 484:484 1 484:484 1 484:484 In this manuscript, we distinguish three statistical goals for therapeutic protein characterization: (1) estimation of site occupancy of modifications in one condition, (2) detection of differential site occupancy between conditions, and (3) estimation of combined site occupancy across multiple modification sites. 28801661 6 90 theme site 1144:1147 arg1 occupancy 1149:1157 differential site occupancy 1131:1157 differential site occupancy in positive and negative controls 1131:1191 The performance was compared to a 'naïve' data analysis approach, by using computer simulation, evaluation of differential site occupancy in positive and negative controls, and comparisons of estimated site occupancy with orthogonal experimental measurements of N-linked glycoforms and total oxidation. 28801661 3 91 theme modification 678:689 arg1 sites 691:695 multiple modification sites 669:695 multiple modification sites 669:695 In this manuscript, we distinguish three statistical goals for therapeutic protein characterization: (1) estimation of site occupancy of modifications in one condition, (2) detection of differential site occupancy between conditions, and (3) estimation of combined site occupancy across multiple modification sites. 28801661 2 92 theme resulting 366:374 arg1 data 376:379 the resulting data 362:379 the resulting data 362:379 Despite its importance, there is currently no consensus on the statistical analysis of the resulting data. 28801661 7 93 theme reproducible 1460:1471 arg1 estimation 1512:1521 reproducible, accurate and efficient site occupancy estimation 1460:1521 reproducible, accurate and efficient site occupancy estimation 1460:1521 The results demonstrated the importance of replicated studies of protein characterization, and of appropriate statistical modeling, for reproducible, accurate and efficient site occupancy estimation and differential analysis. 25635619 4 0 theme other 1108:1112 arg1 indicators 1114:1123 other indicators 1108:1123 other indicators of alternative macrophage activation 1108:1160 However, in mice immunologically sensitized to MDI via prior skin exposure, identical GSH-MDI doses induced substantially greater inflammatory responses, including significantly increased airway eosinophil numbers and mucus production, along with IL-12/IL-23β, chitinases, and other indicators of alternative macrophage activation. 25635619 4 1 theme GSH-MDI 917:923 arg1 doses 925:929 identical GSH-MDI doses 907:929 identical GSH-MDI doses 907:929 However, in mice immunologically sensitized to MDI via prior skin exposure, identical GSH-MDI doses induced substantially greater inflammatory responses, including significantly increased airway eosinophil numbers and mucus production, along with IL-12/IL-23β, chitinases, and other indicators of alternative macrophage activation. 25635619 3 2 theme Chitinase 778:786 arg1 YM-1 788:791 Chitinase YM-1 778:791 Chitinase YM-1 778:791 In naïve mice, a mixture of GSH reaction products with the chemical allergen, methylene-diphenyl diisocyanate (MDI), induced innate immune responses, characterized by significantly increased airway levels of Chitinase YM-1 and IL-12/IL-23β (but not α) subunit. 25635619 1 3 theme chemical 203:210 arg1 cause 212:216 a leading chemical cause 193:216 a leading chemical cause of occupational asthma 193:239 Isocyanates have been a leading chemical cause of occupational asthma since their utility for generating polyurethane was first recognized over 60 years ago, yet the mechanisms of isocyanate asthma pathogenesis remain unclear. 25635619 1 3 theme chemical 203:210 arg1 Isocyanates 171:181 Isocyanates 171:181 Isocyanates 171:181 Isocyanates have been a leading chemical cause of occupational asthma since their utility for generating polyurethane was first recognized over 60 years ago, yet the mechanisms of isocyanate asthma pathogenesis remain unclear. 25635619 4 4 theme skin 892:895 arg1 exposure 897:904 prior skin exposure 886:904 prior skin exposure 886:904 However, in mice immunologically sensitized to MDI via prior skin exposure, identical GSH-MDI doses induced substantially greater inflammatory responses, including significantly increased airway eosinophil numbers and mucus production, along with IL-12/IL-23β, chitinases, and other indicators of alternative macrophage activation. 25635619 7 5 theme MDI 1630:1632 arg1 exposure 1634:1641 MDI exposure 1630:1641 MDI exposure 1630:1641 Together, the data support a possible thiol mediated transcarbamoylating mechanism linking MDI exposure to pathogenic eosinophilic inflammatory responses. 25635619 0 6 theme eosinophilic 137:148 arg1 inflammation 157:168 eosinophilic airway inflammation 137:168 eosinophilic airway inflammation 137:168 Glutathione reaction products with a chemical allergen, methylene-diphenyl diisocyanate, stimulate alternative macrophage activation and eosinophilic airway inflammation. 25635619 3 7 theme reaction 602:609 arg1 products 611:618 GSH reaction products 598:618 GSH reaction products 598:618 In naïve mice, a mixture of GSH reaction products with the chemical allergen, methylene-diphenyl diisocyanate (MDI), induced innate immune responses, characterized by significantly increased airway levels of Chitinase YM-1 and IL-12/IL-23β (but not α) subunit. 25635619 1 8 theme asthma 234:239 arg1 cause 212:216 a leading chemical cause 193:216 a leading chemical cause of occupational asthma 193:239 Isocyanates have been a leading chemical cause of occupational asthma since their utility for generating polyurethane was first recognized over 60 years ago, yet the mechanisms of isocyanate asthma pathogenesis remain unclear. 25635619 1 8 theme asthma 234:239 arg1 Isocyanates 171:181 Isocyanates 171:181 Isocyanates 171:181 Isocyanates have been a leading chemical cause of occupational asthma since their utility for generating polyurethane was first recognized over 60 years ago, yet the mechanisms of isocyanate asthma pathogenesis remain unclear. 25635619 7 9 theme mediated 1583:1590 arg1 mechanism 1612:1620 a possible thiol mediated transcarbamoylating mechanism 1566:1620 a possible thiol mediated transcarbamoylating mechanism linking MDI exposure to pathogenic eosinophilic inflammatory responses 1566:1691 Together, the data support a possible thiol mediated transcarbamoylating mechanism linking MDI exposure to pathogenic eosinophilic inflammatory responses. 25635619 5 10 from site 1277:1280 arg1 albumin 1309:1315 human albumin 1303:1315 human albumin 1303:1315 The "self"-protein albumin in mouse airway fluid was uniquely modified by GSH-MDI at position (414)K, a preferred site of MDI reactivity on human albumin. 25635619 3 11 theme chemical 629:636 arg1 allergen 638:645 the chemical allergen 625:645 the chemical allergen 625:645 In naïve mice, a mixture of GSH reaction products with the chemical allergen, methylene-diphenyl diisocyanate (MDI), induced innate immune responses, characterized by significantly increased airway levels of Chitinase YM-1 and IL-12/IL-23β (but not α) subunit. 25635619 3 11 theme chemical 629:636 arg1 diisocyanate 667:678 methylene-diphenyl diisocyanate 648:678 methylene-diphenyl diisocyanate (MDI) 648:684 In naïve mice, a mixture of GSH reaction products with the chemical allergen, methylene-diphenyl diisocyanate (MDI), induced innate immune responses, characterized by significantly increased airway levels of Chitinase YM-1 and IL-12/IL-23β (but not α) subunit. 25635619 7 12 theme possible 1568:1575 arg1 mechanism 1612:1620 a possible thiol mediated transcarbamoylating mechanism 1566:1620 a possible thiol mediated transcarbamoylating mechanism linking MDI exposure to pathogenic eosinophilic inflammatory responses 1566:1691 Together, the data support a possible thiol mediated transcarbamoylating mechanism linking MDI exposure to pathogenic eosinophilic inflammatory responses. 25635619 4 13 theme greater 953:959 arg1 responses 974:982 substantially greater inflammatory responses 939:982 substantially greater inflammatory responses 939:982 However, in mice immunologically sensitized to MDI via prior skin exposure, identical GSH-MDI doses induced substantially greater inflammatory responses, including significantly increased airway eosinophil numbers and mucus production, along with IL-12/IL-23β, chitinases, and other indicators of alternative macrophage activation. 25635619 4 13 theme greater 953:959 arg1 numbers 1037:1043 significantly increased airway eosinophil numbers 995:1043 significantly increased airway eosinophil numbers 995:1043 However, in mice immunologically sensitized to MDI via prior skin exposure, identical GSH-MDI doses induced substantially greater inflammatory responses, including significantly increased airway eosinophil numbers and mucus production, along with IL-12/IL-23β, chitinases, and other indicators of alternative macrophage activation. 25635619 4 13 theme greater 953:959 arg1 production 1055:1064 mucus production 1049:1064 mucus production 1049:1064 However, in mice immunologically sensitized to MDI via prior skin exposure, identical GSH-MDI doses induced substantially greater inflammatory responses, including significantly increased airway eosinophil numbers and mucus production, along with IL-12/IL-23β, chitinases, and other indicators of alternative macrophage activation. 25635619 0 14 theme methylene-diphenyl 56:73 arg1 allergen 46:53 a chemical allergen 35:53 a chemical allergen 35:53 Glutathione reaction products with a chemical allergen, methylene-diphenyl diisocyanate, stimulate alternative macrophage activation and eosinophilic airway inflammation. 25635619 0 14 theme methylene-diphenyl 56:73 arg1 diisocyanate 75:86 methylene-diphenyl diisocyanate 56:86 methylene-diphenyl diisocyanate 56:86 Glutathione reaction products with a chemical allergen, methylene-diphenyl diisocyanate, stimulate alternative macrophage activation and eosinophilic airway inflammation. 25635619 1 15 theme isocyanate 351:360 arg1 pathogenesis 369:380 isocyanate asthma pathogenesis 351:380 isocyanate asthma pathogenesis 351:380 Isocyanates have been a leading chemical cause of occupational asthma since their utility for generating polyurethane was first recognized over 60 years ago, yet the mechanisms of isocyanate asthma pathogenesis remain unclear. 25635619 2 16 theme tract 543:547 arg1 exposure 560:567 respiratory tract isocyanate exposure 531:567 respiratory tract isocyanate exposure 531:567 The present study provides in vivo evidence that a GSH mediated pathway underlies asthma-like eosinophilic inflammatory responses to respiratory tract isocyanate exposure. 25635619 5 17 dep position 1248:1255 arg1 K 1262:1262 K 1262:1262 position (414)K 1248:1262 The "self"-protein albumin in mouse airway fluid was uniquely modified by GSH-MDI at position (414)K, a preferred site of MDI reactivity on human albumin. 25635619 5 18 theme MDI 1285:1287 arg1 reactivity 1289:1298 MDI reactivity 1285:1298 MDI reactivity 1285:1298 The "self"-protein albumin in mouse airway fluid was uniquely modified by GSH-MDI at position (414)K, a preferred site of MDI reactivity on human albumin. 25635619 1 19 theme pathogenesis 369:380 arg1 mechanisms 337:346 the mechanisms 333:346 the mechanisms of isocyanate asthma pathogenesis 333:380 Isocyanates have been a leading chemical cause of occupational asthma since their utility for generating polyurethane was first recognized over 60 years ago, yet the mechanisms of isocyanate asthma pathogenesis remain unclear. 25635619 4 20 theme increased 1009:1017 arg1 numbers 1037:1043 significantly increased airway eosinophil numbers 995:1043 significantly increased airway eosinophil numbers 995:1043 However, in mice immunologically sensitized to MDI via prior skin exposure, identical GSH-MDI doses induced substantially greater inflammatory responses, including significantly increased airway eosinophil numbers and mucus production, along with IL-12/IL-23β, chitinases, and other indicators of alternative macrophage activation. 25635619 0 21 theme alternative 99:109 arg1 activation 122:131 alternative macrophage activation 99:131 alternative macrophage activation 99:131 Glutathione reaction products with a chemical allergen, methylene-diphenyl diisocyanate, stimulate alternative macrophage activation and eosinophilic airway inflammation. 25635619 4 22 theme eosinophil 1026:1035 arg1 numbers 1037:1043 significantly increased airway eosinophil numbers 995:1043 significantly increased airway eosinophil numbers 995:1043 However, in mice immunologically sensitized to MDI via prior skin exposure, identical GSH-MDI doses induced substantially greater inflammatory responses, including significantly increased airway eosinophil numbers and mucus production, along with IL-12/IL-23β, chitinases, and other indicators of alternative macrophage activation. 25635619 7 23 theme inflammatory 1670:1681 arg1 responses 1683:1691 pathogenic eosinophilic inflammatory responses 1646:1691 pathogenic eosinophilic inflammatory responses 1646:1691 Together, the data support a possible thiol mediated transcarbamoylating mechanism linking MDI exposure to pathogenic eosinophilic inflammatory responses. 25635619 2 24 theme asthma-like 480:490 arg1 responses 518:526 asthma-like eosinophilic inflammatory responses 480:526 asthma-like eosinophilic inflammatory responses to respiratory tract isocyanate exposure 480:567 The present study provides in vivo evidence that a GSH mediated pathway underlies asthma-like eosinophilic inflammatory responses to respiratory tract isocyanate exposure. 25635619 0 25 theme Glutathione 0:10 arg1 products 21:28 Glutathione reaction products 0:28 Glutathione reaction products with a chemical allergen, methylene-diphenyl diisocyanate, 0:87 Glutathione reaction products with a chemical allergen, methylene-diphenyl diisocyanate, stimulate alternative macrophage activation and eosinophilic airway inflammation. 25635619 7 26 theme pathogenic 1646:1655 arg1 responses 1683:1691 pathogenic eosinophilic inflammatory responses 1646:1691 pathogenic eosinophilic inflammatory responses 1646:1691 Together, the data support a possible thiol mediated transcarbamoylating mechanism linking MDI exposure to pathogenic eosinophilic inflammatory responses. 25635619 2 27 theme GSH 449:451 arg1 pathway 462:468 a GSH mediated pathway 447:468 a GSH mediated pathway 447:468 The present study provides in vivo evidence that a GSH mediated pathway underlies asthma-like eosinophilic inflammatory responses to respiratory tract isocyanate exposure. 25635619 3 28 theme innate 695:700 arg1 responses 709:717 innate immune responses 695:717 innate immune responses 695:717 In naïve mice, a mixture of GSH reaction products with the chemical allergen, methylene-diphenyl diisocyanate (MDI), induced innate immune responses, characterized by significantly increased airway levels of Chitinase YM-1 and IL-12/IL-23β (but not α) subunit. 25635619 6 29 theme unique 1419:1424 arg1 GSH 1397:1399 GSH's NH2-terminus 1397:1414 GSH's NH2-terminus 1397:1414 The (414)K-MDI conjugation appears to covalently cross-link GSH to albumin via GSH's NH2-terminus, a unique conformation possibly resulting from cyclized mono(GSH)-MDI or asymmetric (S,N'-linked) bis(GSH)-MDI conjugates. 25635619 6 29 theme unique 1419:1424 arg1 conformation 1426:1437 a unique conformation 1417:1437 a unique conformation possibly resulting from cyclized mono(GSH)-MDI or asymmetric (S,N'-linked) bis(GSH)-MDI conjugates 1417:1536 The (414)K-MDI conjugation appears to covalently cross-link GSH to albumin via GSH's NH2-terminus, a unique conformation possibly resulting from cyclized mono(GSH)-MDI or asymmetric (S,N'-linked) bis(GSH)-MDI conjugates. 25635619 2 30 theme inflammatory 505:516 arg1 responses 518:526 asthma-like eosinophilic inflammatory responses 480:526 asthma-like eosinophilic inflammatory responses to respiratory tract isocyanate exposure 480:567 The present study provides in vivo evidence that a GSH mediated pathway underlies asthma-like eosinophilic inflammatory responses to respiratory tract isocyanate exposure. 25635619 0 31 with products 21:28 arg1 allergen 46:53 a chemical allergen 35:53 a chemical allergen 35:53 Glutathione reaction products with a chemical allergen, methylene-diphenyl diisocyanate, stimulate alternative macrophage activation and eosinophilic airway inflammation. 25635619 0 31 with products 21:28 arg1 diisocyanate 75:86 methylene-diphenyl diisocyanate 56:86 methylene-diphenyl diisocyanate 56:86 Glutathione reaction products with a chemical allergen, methylene-diphenyl diisocyanate, stimulate alternative macrophage activation and eosinophilic airway inflammation. 25635619 4 32 theme activation 1151:1160 arg1 chitinases 1092:1101 chitinases 1092:1101 chitinases 1092:1101 However, in mice immunologically sensitized to MDI via prior skin exposure, identical GSH-MDI doses induced substantially greater inflammatory responses, including significantly increased airway eosinophil numbers and mucus production, along with IL-12/IL-23β, chitinases, and other indicators of alternative macrophage activation. 25635619 4 32 theme activation 1151:1160 arg1 IL-12/IL-23β 1078:1089 IL-12/IL-23β 1078:1089 IL-12/IL-23β 1078:1089 However, in mice immunologically sensitized to MDI via prior skin exposure, identical GSH-MDI doses induced substantially greater inflammatory responses, including significantly increased airway eosinophil numbers and mucus production, along with IL-12/IL-23β, chitinases, and other indicators of alternative macrophage activation. 25635619 4 32 theme activation 1151:1160 arg1 indicators 1114:1123 other indicators 1108:1123 other indicators of alternative macrophage activation 1108:1160 However, in mice immunologically sensitized to MDI via prior skin exposure, identical GSH-MDI doses induced substantially greater inflammatory responses, including significantly increased airway eosinophil numbers and mucus production, along with IL-12/IL-23β, chitinases, and other indicators of alternative macrophage activation. 25635619 6 33 theme asymmetric 1489:1498 arg1 GSH 1518:1520 GSH 1518:1520 GSH 1518:1520 The (414)K-MDI conjugation appears to covalently cross-link GSH to albumin via GSH's NH2-terminus, a unique conformation possibly resulting from cyclized mono(GSH)-MDI or asymmetric (S,N'-linked) bis(GSH)-MDI conjugates. 25635619 6 33 theme asymmetric 1489:1498 arg1 bis 1514:1516 asymmetric (S,N'-linked) bis 1489:1516 bis 1514:1516 The (414)K-MDI conjugation appears to covalently cross-link GSH to albumin via GSH's NH2-terminus, a unique conformation possibly resulting from cyclized mono(GSH)-MDI or asymmetric (S,N'-linked) bis(GSH)-MDI conjugates. 25635619 3 34 theme naïve 573:577 arg1 mice 579:582 naïve mice 573:582 naïve mice 573:582 In naïve mice, a mixture of GSH reaction products with the chemical allergen, methylene-diphenyl diisocyanate (MDI), induced innate immune responses, characterized by significantly increased airway levels of Chitinase YM-1 and IL-12/IL-23β (but not α) subunit. 25635619 5 35 theme preferred 1267:1275 arg1 reactivity 1289:1298 MDI reactivity 1285:1298 MDI reactivity 1285:1298 The "self"-protein albumin in mouse airway fluid was uniquely modified by GSH-MDI at position (414)K, a preferred site of MDI reactivity on human albumin. 25635619 5 35 theme preferred 1267:1275 arg1 position 1248:1255 position (414) 1248:1261 position (414)K 1248:1262 The "self"-protein albumin in mouse airway fluid was uniquely modified by GSH-MDI at position (414)K, a preferred site of MDI reactivity on human albumin. 25635619 5 35 theme preferred 1267:1275 arg1 site 1277:1280 a preferred site 1265:1280 a preferred site of MDI reactivity on human albumin 1265:1315 The "self"-protein albumin in mouse airway fluid was uniquely modified by GSH-MDI at position (414)K, a preferred site of MDI reactivity on human albumin. 25635619 5 36 from albumin 1182:1188 arg1 fluid 1206:1210 mouse airway fluid 1193:1210 mouse airway fluid 1193:1210 The "self"-protein albumin in mouse airway fluid was uniquely modified by GSH-MDI at position (414)K, a preferred site of MDI reactivity on human albumin. 25635619 3 37 theme airway 761:766 arg1 levels 768:773 significantly increased airway levels 737:773 significantly increased airway levels of Chitinase YM-1 737:791 In naïve mice, a mixture of GSH reaction products with the chemical allergen, methylene-diphenyl diisocyanate (MDI), induced innate immune responses, characterized by significantly increased airway levels of Chitinase YM-1 and IL-12/IL-23β (but not α) subunit. 25635619 6 38 theme GSH 1477:1479 arg1 -MDI 1481:1484 cyclized mono(GSH)-MDI 1463:1484 cyclized mono(GSH)-MDI 1463:1484 The (414)K-MDI conjugation appears to covalently cross-link GSH to albumin via GSH's NH2-terminus, a unique conformation possibly resulting from cyclized mono(GSH)-MDI or asymmetric (S,N'-linked) bis(GSH)-MDI conjugates. 25635619 3 39 dep IL-12/IL-23β 797:808 arg1 α 819:819 α 819:819 α 819:819 In naïve mice, a mixture of GSH reaction products with the chemical allergen, methylene-diphenyl diisocyanate (MDI), induced innate immune responses, characterized by significantly increased airway levels of Chitinase YM-1 and IL-12/IL-23β (but not α) subunit. 25635619 4 40 theme alternative 1128:1138 arg1 activation 1151:1160 alternative macrophage activation 1128:1160 alternative macrophage activation 1128:1160 However, in mice immunologically sensitized to MDI via prior skin exposure, identical GSH-MDI doses induced substantially greater inflammatory responses, including significantly increased airway eosinophil numbers and mucus production, along with IL-12/IL-23β, chitinases, and other indicators of alternative macrophage activation. 25635619 6 41 theme mono 1472:1475 arg1 -MDI 1481:1484 cyclized mono(GSH)-MDI 1463:1484 cyclized mono(GSH)-MDI 1463:1484 The (414)K-MDI conjugation appears to covalently cross-link GSH to albumin via GSH's NH2-terminus, a unique conformation possibly resulting from cyclized mono(GSH)-MDI or asymmetric (S,N'-linked) bis(GSH)-MDI conjugates. 25635619 4 42 theme identical 907:915 arg1 doses 925:929 identical GSH-MDI doses 907:929 identical GSH-MDI doses 907:929 However, in mice immunologically sensitized to MDI via prior skin exposure, identical GSH-MDI doses induced substantially greater inflammatory responses, including significantly increased airway eosinophil numbers and mucus production, along with IL-12/IL-23β, chitinases, and other indicators of alternative macrophage activation. 25635619 3 43 theme YM-1 788:791 arg1 levels 768:773 significantly increased airway levels 737:773 significantly increased airway levels of Chitinase YM-1 737:791 In naïve mice, a mixture of GSH reaction products with the chemical allergen, methylene-diphenyl diisocyanate (MDI), induced innate immune responses, characterized by significantly increased airway levels of Chitinase YM-1 and IL-12/IL-23β (but not α) subunit. 25635619 3 43 theme YM-1 788:791 arg1 subunit 822:828 IL-12/IL-23β (but not α) subunit 797:828 IL-12/IL-23β (but not α) subunit 797:828 In naïve mice, a mixture of GSH reaction products with the chemical allergen, methylene-diphenyl diisocyanate (MDI), induced innate immune responses, characterized by significantly increased airway levels of Chitinase YM-1 and IL-12/IL-23β (but not α) subunit. 25635619 1 44 theme leading 195:201 arg1 cause 212:216 a leading chemical cause 193:216 a leading chemical cause of occupational asthma 193:239 Isocyanates have been a leading chemical cause of occupational asthma since their utility for generating polyurethane was first recognized over 60 years ago, yet the mechanisms of isocyanate asthma pathogenesis remain unclear. 25635619 1 44 theme leading 195:201 arg1 Isocyanates 171:181 Isocyanates 171:181 Isocyanates 171:181 Isocyanates have been a leading chemical cause of occupational asthma since their utility for generating polyurethane was first recognized over 60 years ago, yet the mechanisms of isocyanate asthma pathogenesis remain unclear. 25635619 4 45 theme mucus 1049:1053 arg1 production 1055:1064 mucus production 1049:1064 mucus production 1049:1064 However, in mice immunologically sensitized to MDI via prior skin exposure, identical GSH-MDI doses induced substantially greater inflammatory responses, including significantly increased airway eosinophil numbers and mucus production, along with IL-12/IL-23β, chitinases, and other indicators of alternative macrophage activation. 25635619 3 46 theme products 611:618 arg1 mixture 587:593 a mixture 585:593 a mixture of GSH reaction products with the chemical allergen, methylene-diphenyl diisocyanate (MDI), 585:685 In naïve mice, a mixture of GSH reaction products with the chemical allergen, methylene-diphenyl diisocyanate (MDI), induced innate immune responses, characterized by significantly increased airway levels of Chitinase YM-1 and IL-12/IL-23β (but not α) subunit. 25635619 5 47 theme mouse 1193:1197 arg1 fluid 1206:1210 mouse airway fluid 1193:1210 mouse airway fluid 1193:1210 The "self"-protein albumin in mouse airway fluid was uniquely modified by GSH-MDI at position (414)K, a preferred site of MDI reactivity on human albumin. 25635619 6 48 link N'-linked 1503:1511 arg1 GSH 1518:1520 GSH 1518:1520 GSH 1518:1520 The (414)K-MDI conjugation appears to covalently cross-link GSH to albumin via GSH's NH2-terminus, a unique conformation possibly resulting from cyclized mono(GSH)-MDI or asymmetric (S,N'-linked) bis(GSH)-MDI conjugates. 25635619 6 48 link N'-linked 1503:1511 arg1 bis 1514:1516 asymmetric (S,N'-linked) bis 1489:1516 bis 1514:1516 The (414)K-MDI conjugation appears to covalently cross-link GSH to albumin via GSH's NH2-terminus, a unique conformation possibly resulting from cyclized mono(GSH)-MDI or asymmetric (S,N'-linked) bis(GSH)-MDI conjugates. 25635619 0 49 theme airway 150:155 arg1 inflammation 157:168 eosinophilic airway inflammation 137:168 eosinophilic airway inflammation 137:168 Glutathione reaction products with a chemical allergen, methylene-diphenyl diisocyanate, stimulate alternative macrophage activation and eosinophilic airway inflammation. 25635619 3 50 theme GSH 598:600 arg1 products 611:618 GSH reaction products 598:618 GSH reaction products 598:618 In naïve mice, a mixture of GSH reaction products with the chemical allergen, methylene-diphenyl diisocyanate (MDI), induced innate immune responses, characterized by significantly increased airway levels of Chitinase YM-1 and IL-12/IL-23β (but not α) subunit. 25635619 6 51 theme N'-linked 1503:1511 arg1 GSH 1518:1520 GSH 1518:1520 GSH 1518:1520 The (414)K-MDI conjugation appears to covalently cross-link GSH to albumin via GSH's NH2-terminus, a unique conformation possibly resulting from cyclized mono(GSH)-MDI or asymmetric (S,N'-linked) bis(GSH)-MDI conjugates. 25635619 6 51 theme N'-linked 1503:1511 arg1 bis 1514:1516 asymmetric (S,N'-linked) bis 1489:1516 bis 1514:1516 The (414)K-MDI conjugation appears to covalently cross-link GSH to albumin via GSH's NH2-terminus, a unique conformation possibly resulting from cyclized mono(GSH)-MDI or asymmetric (S,N'-linked) bis(GSH)-MDI conjugates. 25635619 1 52 theme occupational 221:232 arg1 asthma 234:239 occupational asthma 221:239 occupational asthma 221:239 Isocyanates have been a leading chemical cause of occupational asthma since their utility for generating polyurethane was first recognized over 60 years ago, yet the mechanisms of isocyanate asthma pathogenesis remain unclear. 25635619 7 53 theme transcarbamoylating 1592:1610 arg1 mechanism 1612:1620 a possible thiol mediated transcarbamoylating mechanism 1566:1620 a possible thiol mediated transcarbamoylating mechanism linking MDI exposure to pathogenic eosinophilic inflammatory responses 1566:1691 Together, the data support a possible thiol mediated transcarbamoylating mechanism linking MDI exposure to pathogenic eosinophilic inflammatory responses. 25635619 4 54 theme inflammatory 961:972 arg1 responses 974:982 substantially greater inflammatory responses 939:982 substantially greater inflammatory responses 939:982 However, in mice immunologically sensitized to MDI via prior skin exposure, identical GSH-MDI doses induced substantially greater inflammatory responses, including significantly increased airway eosinophil numbers and mucus production, along with IL-12/IL-23β, chitinases, and other indicators of alternative macrophage activation. 25635619 4 54 theme inflammatory 961:972 arg1 numbers 1037:1043 significantly increased airway eosinophil numbers 995:1043 significantly increased airway eosinophil numbers 995:1043 However, in mice immunologically sensitized to MDI via prior skin exposure, identical GSH-MDI doses induced substantially greater inflammatory responses, including significantly increased airway eosinophil numbers and mucus production, along with IL-12/IL-23β, chitinases, and other indicators of alternative macrophage activation. 25635619 4 54 theme inflammatory 961:972 arg1 production 1055:1064 mucus production 1049:1064 mucus production 1049:1064 However, in mice immunologically sensitized to MDI via prior skin exposure, identical GSH-MDI doses induced substantially greater inflammatory responses, including significantly increased airway eosinophil numbers and mucus production, along with IL-12/IL-23β, chitinases, and other indicators of alternative macrophage activation. 25635619 3 55 theme IL-12/IL-23β 797:808 arg1 subunit 822:828 IL-12/IL-23β (but not α) subunit 797:828 IL-12/IL-23β (but not α) subunit 797:828 In naïve mice, a mixture of GSH reaction products with the chemical allergen, methylene-diphenyl diisocyanate (MDI), induced innate immune responses, characterized by significantly increased airway levels of Chitinase YM-1 and IL-12/IL-23β (but not α) subunit. 25635619 6 56 theme S 1501:1501 arg1 GSH 1518:1520 GSH 1518:1520 GSH 1518:1520 The (414)K-MDI conjugation appears to covalently cross-link GSH to albumin via GSH's NH2-terminus, a unique conformation possibly resulting from cyclized mono(GSH)-MDI or asymmetric (S,N'-linked) bis(GSH)-MDI conjugates. 25635619 6 56 theme S 1501:1501 arg1 bis 1514:1516 asymmetric (S,N'-linked) bis 1489:1516 bis 1514:1516 The (414)K-MDI conjugation appears to covalently cross-link GSH to albumin via GSH's NH2-terminus, a unique conformation possibly resulting from cyclized mono(GSH)-MDI or asymmetric (S,N'-linked) bis(GSH)-MDI conjugates. 25635619 5 57 mod modified 1225:1232 arg1 albumin 1182:1188 The "self"-protein albumin 1163:1188 The "self"-protein albumin in mouse airway fluid 1163:1210 The "self"-protein albumin in mouse airway fluid was uniquely modified by GSH-MDI at position (414)K, a preferred site of MDI reactivity on human albumin. 25635619 5 57 mod modified 1225:1232 arg3 GSH-MDI 1237:1243 GSH-MDI 1237:1243 GSH-MDI 1237:1243 The "self"-protein albumin in mouse airway fluid was uniquely modified by GSH-MDI at position (414)K, a preferred site of MDI reactivity on human albumin. 25635619 6 58 theme K-MDI 1327:1331 arg1 conjugation 1333:1343 The (414)K-MDI conjugation 1318:1343 The (414)K-MDI conjugation 1318:1343 The (414)K-MDI conjugation appears to covalently cross-link GSH to albumin via GSH's NH2-terminus, a unique conformation possibly resulting from cyclized mono(GSH)-MDI or asymmetric (S,N'-linked) bis(GSH)-MDI conjugates. 25635619 5 59 theme human 1303:1307 arg1 albumin 1309:1315 human albumin 1303:1315 human albumin 1303:1315 The "self"-protein albumin in mouse airway fluid was uniquely modified by GSH-MDI at position (414)K, a preferred site of MDI reactivity on human albumin. 25635619 6 60 theme 414 1323:1325 arg1 conjugation 1333:1343 The (414)K-MDI conjugation 1318:1343 The (414)K-MDI conjugation 1318:1343 The (414)K-MDI conjugation appears to covalently cross-link GSH to albumin via GSH's NH2-terminus, a unique conformation possibly resulting from cyclized mono(GSH)-MDI or asymmetric (S,N'-linked) bis(GSH)-MDI conjugates. 25635619 6 61 theme NH2-terminus 1403:1414 arg1 GSH 1397:1399 GSH's NH2-terminus 1397:1414 GSH's NH2-terminus 1397:1414 The (414)K-MDI conjugation appears to covalently cross-link GSH to albumin via GSH's NH2-terminus, a unique conformation possibly resulting from cyclized mono(GSH)-MDI or asymmetric (S,N'-linked) bis(GSH)-MDI conjugates. 25635619 6 61 theme NH2-terminus 1403:1414 arg1 conformation 1426:1437 a unique conformation 1417:1437 a unique conformation possibly resulting from cyclized mono(GSH)-MDI or asymmetric (S,N'-linked) bis(GSH)-MDI conjugates 1417:1536 The (414)K-MDI conjugation appears to covalently cross-link GSH to albumin via GSH's NH2-terminus, a unique conformation possibly resulting from cyclized mono(GSH)-MDI or asymmetric (S,N'-linked) bis(GSH)-MDI conjugates. 25635619 3 62 theme methylene-diphenyl 648:665 arg1 allergen 638:645 the chemical allergen 625:645 the chemical allergen 625:645 In naïve mice, a mixture of GSH reaction products with the chemical allergen, methylene-diphenyl diisocyanate (MDI), induced innate immune responses, characterized by significantly increased airway levels of Chitinase YM-1 and IL-12/IL-23β (but not α) subunit. 25635619 3 62 theme methylene-diphenyl 648:665 arg1 diisocyanate 667:678 methylene-diphenyl diisocyanate 648:678 methylene-diphenyl diisocyanate (MDI) 648:684 In naïve mice, a mixture of GSH reaction products with the chemical allergen, methylene-diphenyl diisocyanate (MDI), induced innate immune responses, characterized by significantly increased airway levels of Chitinase YM-1 and IL-12/IL-23β (but not α) subunit. 25635619 3 62 theme methylene-diphenyl 648:665 arg1 MDI 681:683 MDI 681:683 MDI 681:683 In naïve mice, a mixture of GSH reaction products with the chemical allergen, methylene-diphenyl diisocyanate (MDI), induced innate immune responses, characterized by significantly increased airway levels of Chitinase YM-1 and IL-12/IL-23β (but not α) subunit. 25635619 2 63 theme isocyanate 549:558 arg1 exposure 560:567 respiratory tract isocyanate exposure 531:567 respiratory tract isocyanate exposure 531:567 The present study provides in vivo evidence that a GSH mediated pathway underlies asthma-like eosinophilic inflammatory responses to respiratory tract isocyanate exposure. 25635619 1 64 theme asthma 362:367 arg1 pathogenesis 369:380 isocyanate asthma pathogenesis 351:380 isocyanate asthma pathogenesis 351:380 Isocyanates have been a leading chemical cause of occupational asthma since their utility for generating polyurethane was first recognized over 60 years ago, yet the mechanisms of isocyanate asthma pathogenesis remain unclear. 25635619 6 65 theme -MDI 1522:1525 arg1 conjugates 1527:1536 -MDI conjugates 1522:1536 -MDI conjugates 1522:1536 The (414)K-MDI conjugation appears to covalently cross-link GSH to albumin via GSH's NH2-terminus, a unique conformation possibly resulting from cyclized mono(GSH)-MDI or asymmetric (S,N'-linked) bis(GSH)-MDI conjugates. 25635619 2 66 theme respiratory 531:541 arg1 exposure 560:567 respiratory tract isocyanate exposure 531:567 respiratory tract isocyanate exposure 531:567 The present study provides in vivo evidence that a GSH mediated pathway underlies asthma-like eosinophilic inflammatory responses to respiratory tract isocyanate exposure. 25635619 5 67 theme reactivity 1289:1298 arg1 reactivity 1289:1298 MDI reactivity 1285:1298 MDI reactivity 1285:1298 The "self"-protein albumin in mouse airway fluid was uniquely modified by GSH-MDI at position (414)K, a preferred site of MDI reactivity on human albumin. 25635619 5 67 theme reactivity 1289:1298 arg1 position 1248:1255 position (414) 1248:1261 position (414)K 1248:1262 The "self"-protein albumin in mouse airway fluid was uniquely modified by GSH-MDI at position (414)K, a preferred site of MDI reactivity on human albumin. 25635619 5 67 theme reactivity 1289:1298 arg1 site 1277:1280 a preferred site 1265:1280 a preferred site of MDI reactivity on human albumin 1265:1315 The "self"-protein albumin in mouse airway fluid was uniquely modified by GSH-MDI at position (414)K, a preferred site of MDI reactivity on human albumin. 25635619 0 68 theme macrophage 111:120 arg1 activation 122:131 alternative macrophage activation 99:131 alternative macrophage activation 99:131 Glutathione reaction products with a chemical allergen, methylene-diphenyl diisocyanate, stimulate alternative macrophage activation and eosinophilic airway inflammation. 25635619 5 69 theme airway 1199:1204 arg1 fluid 1206:1210 mouse airway fluid 1193:1210 mouse airway fluid 1193:1210 The "self"-protein albumin in mouse airway fluid was uniquely modified by GSH-MDI at position (414)K, a preferred site of MDI reactivity on human albumin. 25635619 5 70 theme self 1168:1171 arg1 albumin 1182:1188 The "self"-protein albumin 1163:1188 The "self"-protein albumin in mouse airway fluid 1163:1210 The "self"-protein albumin in mouse airway fluid was uniquely modified by GSH-MDI at position (414)K, a preferred site of MDI reactivity on human albumin. 25635619 4 71 theme airway 1019:1024 arg1 numbers 1037:1043 significantly increased airway eosinophil numbers 995:1043 significantly increased airway eosinophil numbers 995:1043 However, in mice immunologically sensitized to MDI via prior skin exposure, identical GSH-MDI doses induced substantially greater inflammatory responses, including significantly increased airway eosinophil numbers and mucus production, along with IL-12/IL-23β, chitinases, and other indicators of alternative macrophage activation. 25635619 2 72 theme in 425:426 arg1 evidence 433:440 in vivo evidence that a GSH mediated pathway underlies asthma-like eosinophilic inflammatory responses to respiratory tract isocyanate exposure 425:567 in vivo evidence that a GSH mediated pathway underlies asthma-like eosinophilic inflammatory responses to respiratory tract isocyanate exposure 425:567 The present study provides in vivo evidence that a GSH mediated pathway underlies asthma-like eosinophilic inflammatory responses to respiratory tract isocyanate exposure. 25635619 0 73 theme reaction 12:19 arg1 products 21:28 Glutathione reaction products 0:28 Glutathione reaction products with a chemical allergen, methylene-diphenyl diisocyanate, 0:87 Glutathione reaction products with a chemical allergen, methylene-diphenyl diisocyanate, stimulate alternative macrophage activation and eosinophilic airway inflammation. 25635619 5 74 theme -protein 1173:1180 arg1 albumin 1182:1188 The "self"-protein albumin 1163:1188 The "self"-protein albumin in mouse airway fluid 1163:1210 The "self"-protein albumin in mouse airway fluid was uniquely modified by GSH-MDI at position (414)K, a preferred site of MDI reactivity on human albumin. 25635619 7 75 theme eosinophilic 1657:1668 arg1 responses 1683:1691 pathogenic eosinophilic inflammatory responses 1646:1691 pathogenic eosinophilic inflammatory responses 1646:1691 Together, the data support a possible thiol mediated transcarbamoylating mechanism linking MDI exposure to pathogenic eosinophilic inflammatory responses. 25635619 2 76 theme mediated 453:460 arg1 pathway 462:468 a GSH mediated pathway 447:468 a GSH mediated pathway 447:468 The present study provides in vivo evidence that a GSH mediated pathway underlies asthma-like eosinophilic inflammatory responses to respiratory tract isocyanate exposure. 25635619 2 77 theme present 402:408 arg1 study 410:414 The present study 398:414 The present study 398:414 The present study provides in vivo evidence that a GSH mediated pathway underlies asthma-like eosinophilic inflammatory responses to respiratory tract isocyanate exposure. 25635619 0 78 theme chemical 37:44 arg1 allergen 46:53 a chemical allergen 35:53 a chemical allergen 35:53 Glutathione reaction products with a chemical allergen, methylene-diphenyl diisocyanate, stimulate alternative macrophage activation and eosinophilic airway inflammation. 25635619 0 78 theme chemical 37:44 arg1 diisocyanate 75:86 methylene-diphenyl diisocyanate 56:86 methylene-diphenyl diisocyanate 56:86 Glutathione reaction products with a chemical allergen, methylene-diphenyl diisocyanate, stimulate alternative macrophage activation and eosinophilic airway inflammation. 25635619 3 79 with mixture 587:593 arg1 allergen 638:645 the chemical allergen 625:645 the chemical allergen 625:645 In naïve mice, a mixture of GSH reaction products with the chemical allergen, methylene-diphenyl diisocyanate (MDI), induced innate immune responses, characterized by significantly increased airway levels of Chitinase YM-1 and IL-12/IL-23β (but not α) subunit. 25635619 3 79 with mixture 587:593 arg1 diisocyanate 667:678 methylene-diphenyl diisocyanate 648:678 methylene-diphenyl diisocyanate (MDI) 648:684 In naïve mice, a mixture of GSH reaction products with the chemical allergen, methylene-diphenyl diisocyanate (MDI), induced innate immune responses, characterized by significantly increased airway levels of Chitinase YM-1 and IL-12/IL-23β (but not α) subunit. 25635619 7 80 theme thiol 1577:1581 arg1 mechanism 1612:1620 a possible thiol mediated transcarbamoylating mechanism 1566:1620 a possible thiol mediated transcarbamoylating mechanism linking MDI exposure to pathogenic eosinophilic inflammatory responses 1566:1691 Together, the data support a possible thiol mediated transcarbamoylating mechanism linking MDI exposure to pathogenic eosinophilic inflammatory responses. 25635619 4 81 theme prior 886:890 arg1 exposure 897:904 prior skin exposure 886:904 prior skin exposure 886:904 However, in mice immunologically sensitized to MDI via prior skin exposure, identical GSH-MDI doses induced substantially greater inflammatory responses, including significantly increased airway eosinophil numbers and mucus production, along with IL-12/IL-23β, chitinases, and other indicators of alternative macrophage activation. 25635619 2 82 theme eosinophilic 492:503 arg1 responses 518:526 asthma-like eosinophilic inflammatory responses 480:526 asthma-like eosinophilic inflammatory responses to respiratory tract isocyanate exposure 480:567 The present study provides in vivo evidence that a GSH mediated pathway underlies asthma-like eosinophilic inflammatory responses to respiratory tract isocyanate exposure. 25635619 4 83 theme macrophage 1140:1149 arg1 activation 1151:1160 alternative macrophage activation 1128:1160 alternative macrophage activation 1128:1160 However, in mice immunologically sensitized to MDI via prior skin exposure, identical GSH-MDI doses induced substantially greater inflammatory responses, including significantly increased airway eosinophil numbers and mucus production, along with IL-12/IL-23β, chitinases, and other indicators of alternative macrophage activation. 25635619 3 84 theme immune 702:707 arg1 responses 709:717 innate immune responses 695:717 innate immune responses 695:717 In naïve mice, a mixture of GSH reaction products with the chemical allergen, methylene-diphenyl diisocyanate (MDI), induced innate immune responses, characterized by significantly increased airway levels of Chitinase YM-1 and IL-12/IL-23β (but not α) subunit. 25635619 6 85 dep -MDI 1481:1484 arg1 conjugates 1527:1536 -MDI conjugates 1522:1536 -MDI conjugates 1522:1536 The (414)K-MDI conjugation appears to covalently cross-link GSH to albumin via GSH's NH2-terminus, a unique conformation possibly resulting from cyclized mono(GSH)-MDI or asymmetric (S,N'-linked) bis(GSH)-MDI conjugates. 25635619 3 86 theme increased 751:759 arg1 levels 768:773 significantly increased airway levels 737:773 significantly increased airway levels of Chitinase YM-1 737:791 In naïve mice, a mixture of GSH reaction products with the chemical allergen, methylene-diphenyl diisocyanate (MDI), induced innate immune responses, characterized by significantly increased airway levels of Chitinase YM-1 and IL-12/IL-23β (but not α) subunit. 25635619 2 87 dep in 425:426 arg1 vivo 428:431 vivo 428:431 vivo 428:431 The present study provides in vivo evidence that a GSH mediated pathway underlies asthma-like eosinophilic inflammatory responses to respiratory tract isocyanate exposure. 25635619 6 88 theme cyclized 1463:1470 arg1 -MDI 1481:1484 cyclized mono(GSH)-MDI 1463:1484 cyclized mono(GSH)-MDI 1463:1484 The (414)K-MDI conjugation appears to covalently cross-link GSH to albumin via GSH's NH2-terminus, a unique conformation possibly resulting from cyclized mono(GSH)-MDI or asymmetric (S,N'-linked) bis(GSH)-MDI conjugates. 24832382 0 0 theme proper 154:159 arg1 processing 167:176 proper lipid processing 154:176 proper lipid processing 154:176 Surface oxidation under ambient air--not only a fast and economical method to identify double bond positions in unsaturated lipids but also a reminder of proper lipid processing. 24832382 5 1 theme conditions 645:654 arg1 Investigations 623:636 Investigations 623:636 Investigations of the conditions controlling the appearance of these products 623:699 Investigations of the conditions controlling the appearance of these products indicated that the surface oxidation depends on light and ambient air. 24832382 1 2 theme unsaturated 253:263 arg1 lipids 265:270 unsaturated lipids 253:270 unsaturated lipids 253:270 A simple, fast approach elucidated carbon-carbon double bond positions in unsaturated lipids. 24832382 9 3 theme sites 1434:1438 arg1 assignment 1396:1405 assignment 1396:1405 assignment of the native unsaturation sites 1396:1438 Co-localization of the starting lipids and their oxidation products after TLC separation allowed assignment of the native unsaturation sites. 24832382 8 4 theme Direct 1144:1149 arg1 sampling 1151:1158 Direct sampling 1144:1158 Direct sampling by thin-layer chromatography (TLC)-ESI-MS 1144:1200 Direct sampling by thin-layer chromatography (TLC)-ESI-MS provides a powerful approach to elucidate detailed structural information on biological samples. 24832382 2 5 theme various 300:306 arg1 surfaces 308:315 various surfaces 300:315 various surfaces 300:315 Lipids were deposited onto various surfaces and the products from their oxidation in ambient air were observed by electrospray ionization (ESI) mass spectrometry (MS). 24832382 7 6 theme isolated 1089:1096 arg1 bond 1105:1108 the isolated double bond 1085:1108 the isolated double bond in the N-linked fatty acyl chain 1085:1141 The 3-hydroxyl group in the sphingoid base of sulfatides offered some protection from oxidation for the Δ4,5-double bond, slowing its oxidation rate relative to that of the isolated double bond in the N-linked fatty acyl chain. 24832382 4 7 theme certain 607:613 arg1 lipids 615:620 certain lipids 607:620 certain lipids 607:620 Ozonides and carboxylic acids were generated in certain lipids. 24832382 10 8 theme oxidation 1589:1597 arg1 products 1599:1606 their oxidation products 1583:1606 their oxidation products 1583:1606 Phosphatidylserine and N,N-dimethyl phosphatidylethanolamine isomers in a bovine brain total lipid extract were distinguished on the basis of their oxidation products. 24832382 5 9 theme products 692:699 arg1 appearance 672:681 the appearance 668:681 the appearance of these products 668:699 Investigations of the conditions controlling the appearance of these products indicated that the surface oxidation depends on light and ambient air. 24832382 3 10 theme cleaved 528:534 arg1 positions 548:556 the cleaved double bond positions 524:556 the cleaved double bond positions 524:556 The most common oxidative products, aldehydes, were detected as transformations at the cleaved double bond positions. 24832382 1 11 theme simple 181:186 arg1 approach 194:201 A simple, fast approach 179:201 A simple, fast approach 179:201 A simple, fast approach elucidated carbon-carbon double bond positions in unsaturated lipids. 24832382 8 12 theme chromatography 1174:1187 arg1 -ESI-MS 1194:1200 thin-layer chromatography (TLC)-ESI-MS 1163:1200 thin-layer chromatography (TLC)-ESI-MS 1163:1200 Direct sampling by thin-layer chromatography (TLC)-ESI-MS provides a powerful approach to elucidate detailed structural information on biological samples. 24832382 1 13 from positions 240:248 arg1 lipids 265:270 unsaturated lipids 253:270 unsaturated lipids 253:270 A simple, fast approach elucidated carbon-carbon double bond positions in unsaturated lipids. 24832382 0 14 theme ambient 24:30 arg1 air--not 32:39 ambient air--not 24:39 ambient air--not 24:39 Surface oxidation under ambient air--not only a fast and economical method to identify double bond positions in unsaturated lipids but also a reminder of proper lipid processing. 24832382 8 15 theme structural 1253:1262 arg1 information 1264:1274 detailed structural information 1244:1274 detailed structural information on biological samples 1244:1296 Direct sampling by thin-layer chromatography (TLC)-ESI-MS provides a powerful approach to elucidate detailed structural information on biological samples. 24832382 7 16 theme Δ4,5-double 1020:1030 arg1 bond 1032:1035 the Δ4,5-double bond 1016:1035 the Δ4,5-double bond 1016:1035 The 3-hydroxyl group in the sphingoid base of sulfatides offered some protection from oxidation for the Δ4,5-double bond, slowing its oxidation rate relative to that of the isolated double bond in the N-linked fatty acyl chain. 24832382 6 17 theme unsaturated 896:906 arg1 lipids 908:913 unsaturated lipids 896:913 unsaturated lipids 896:913 Since the lipid oxidation was slower in a high concentration of ozone, singlet oxygen appeared to be a parallel oxidant for unsaturated lipids. 24832382 11 18 theme artifactual 1755:1765 arg1 oxidation 1767:1775 artifactual oxidation 1755:1775 artifactual oxidation after the plate development 1755:1803 Meanwhile, the findings reported herein reveal a potential pitfall in the assignment of structures to lipids extracted from TLC plates because of artifactual oxidation after the plate development. 24832382 7 19 theme sphingoid 944:952 arg1 base 954:957 the sphingoid base 940:957 the sphingoid base of sulfatides 940:971 The 3-hydroxyl group in the sphingoid base of sulfatides offered some protection from oxidation for the Δ4,5-double bond, slowing its oxidation rate relative to that of the isolated double bond in the N-linked fatty acyl chain. 24832382 7 20 from bond 1105:1108 arg1 chain 1137:1141 the N-linked fatty acyl chain 1113:1141 the N-linked fatty acyl chain 1113:1141 The 3-hydroxyl group in the sphingoid base of sulfatides offered some protection from oxidation for the Δ4,5-double bond, slowing its oxidation rate relative to that of the isolated double bond in the N-linked fatty acyl chain. 24832382 11 21 theme plate 1787:1791 arg1 development 1793:1803 the plate development 1783:1803 the plate development 1783:1803 Meanwhile, the findings reported herein reveal a potential pitfall in the assignment of structures to lipids extracted from TLC plates because of artifactual oxidation after the plate development. 24832382 5 22 theme ambient 759:765 arg1 air 767:769 ambient air 759:769 ambient air 759:769 Investigations of the conditions controlling the appearance of these products indicated that the surface oxidation depends on light and ambient air. 24832382 0 23 theme processing 167:176 arg1 lipids 124:129 unsaturated lipids 112:129 unsaturated lipids but also a reminder of proper lipid processing 112:176 Surface oxidation under ambient air--not only a fast and economical method to identify double bond positions in unsaturated lipids but also a reminder of proper lipid processing. 24832382 0 23 theme processing 167:176 arg1 reminder 142:149 a reminder 140:149 unsaturated lipids but also a reminder of proper lipid processing 112:176 Surface oxidation under ambient air--not only a fast and economical method to identify double bond positions in unsaturated lipids but also a reminder of proper lipid processing. 24832382 5 24 theme surface 720:726 arg1 oxidation 728:736 the surface oxidation 716:736 the surface oxidation 716:736 Investigations of the conditions controlling the appearance of these products indicated that the surface oxidation depends on light and ambient air. 24832382 7 25 theme 3-hydroxyl 920:929 arg1 group 931:935 The 3-hydroxyl group 916:935 The 3-hydroxyl group in the sphingoid base of sulfatides 916:971 The 3-hydroxyl group in the sphingoid base of sulfatides offered some protection from oxidation for the Δ4,5-double bond, slowing its oxidation rate relative to that of the isolated double bond in the N-linked fatty acyl chain. 24832382 9 26 theme native 1414:1419 arg1 sites 1434:1438 the native unsaturation sites 1410:1438 the native unsaturation sites 1410:1438 Co-localization of the starting lipids and their oxidation products after TLC separation allowed assignment of the native unsaturation sites. 24832382 11 27 from pitfall 1668:1674 arg1 assignment 1683:1692 the assignment 1679:1692 the assignment of structures to lipids extracted from TLC plates because of artifactual oxidation after the plate development 1679:1803 Meanwhile, the findings reported herein reveal a potential pitfall in the assignment of structures to lipids extracted from TLC plates because of artifactual oxidation after the plate development. 24832382 10 28 theme N 1464:1464 arg1 isomers 1502:1508 N,N-dimethyl phosphatidylethanolamine isomers 1464:1508 N,N-dimethyl phosphatidylethanolamine isomers 1464:1508 Phosphatidylserine and N,N-dimethyl phosphatidylethanolamine isomers in a bovine brain total lipid extract were distinguished on the basis of their oxidation products. 24832382 0 29 theme Surface 0:6 arg1 oxidation 8:16 Surface oxidation 0:16 Surface oxidation under ambient air--not 0:39 Surface oxidation under ambient air--not only a fast and economical method to identify double bond positions in unsaturated lipids but also a reminder of proper lipid processing. 24832382 2 30 theme mass 417:420 arg1 spectrometry 422:433 electrospray ionization (ESI) mass spectrometry 387:433 electrospray ionization (ESI) mass spectrometry (MS) 387:438 Lipids were deposited onto various surfaces and the products from their oxidation in ambient air were observed by electrospray ionization (ESI) mass spectrometry (MS). 24832382 2 30 theme mass 417:420 arg1 MS 436:437 MS 436:437 MS 436:437 Lipids were deposited onto various surfaces and the products from their oxidation in ambient air were observed by electrospray ionization (ESI) mass spectrometry (MS). 24832382 2 31 theme ESI 412:414 arg1 spectrometry 422:433 electrospray ionization (ESI) mass spectrometry 387:433 electrospray ionization (ESI) mass spectrometry (MS) 387:438 Lipids were deposited onto various surfaces and the products from their oxidation in ambient air were observed by electrospray ionization (ESI) mass spectrometry (MS). 24832382 2 31 theme ESI 412:414 arg1 MS 436:437 MS 436:437 MS 436:437 Lipids were deposited onto various surfaces and the products from their oxidation in ambient air were observed by electrospray ionization (ESI) mass spectrometry (MS). 24832382 7 32 theme fatty 1126:1130 arg1 chain 1137:1141 the N-linked fatty acyl chain 1113:1141 the N-linked fatty acyl chain 1113:1141 The 3-hydroxyl group in the sphingoid base of sulfatides offered some protection from oxidation for the Δ4,5-double bond, slowing its oxidation rate relative to that of the isolated double bond in the N-linked fatty acyl chain. 24832382 9 33 theme starting 1322:1329 arg1 lipids 1331:1336 the starting lipids 1318:1336 the starting lipids 1318:1336 Co-localization of the starting lipids and their oxidation products after TLC separation allowed assignment of the native unsaturation sites. 24832382 6 34 theme singlet 843:849 arg1 oxygen 851:856 singlet oxygen 843:856 singlet oxygen 843:856 Since the lipid oxidation was slower in a high concentration of ozone, singlet oxygen appeared to be a parallel oxidant for unsaturated lipids. 24832382 6 34 theme singlet 843:849 arg1 oxidant 884:890 a parallel oxidant 873:890 a parallel oxidant for unsaturated lipids 873:913 Since the lipid oxidation was slower in a high concentration of ozone, singlet oxygen appeared to be a parallel oxidant for unsaturated lipids. 24832382 2 35 theme ionization 400:409 arg1 spectrometry 422:433 electrospray ionization (ESI) mass spectrometry 387:433 electrospray ionization (ESI) mass spectrometry (MS) 387:438 Lipids were deposited onto various surfaces and the products from their oxidation in ambient air were observed by electrospray ionization (ESI) mass spectrometry (MS). 24832382 2 35 theme ionization 400:409 arg1 MS 436:437 MS 436:437 MS 436:437 Lipids were deposited onto various surfaces and the products from their oxidation in ambient air were observed by electrospray ionization (ESI) mass spectrometry (MS). 24832382 6 36 theme ozone 836:840 arg1 concentration 819:831 a high concentration 812:831 a high concentration of ozone 812:840 Since the lipid oxidation was slower in a high concentration of ozone, singlet oxygen appeared to be a parallel oxidant for unsaturated lipids. 24832382 10 37 theme lipid 1534:1538 arg1 extract 1540:1546 a bovine brain total lipid extract 1513:1546 a bovine brain total lipid extract 1513:1546 Phosphatidylserine and N,N-dimethyl phosphatidylethanolamine isomers in a bovine brain total lipid extract were distinguished on the basis of their oxidation products. 24832382 11 38 theme structures 1697:1706 arg1 assignment 1683:1692 the assignment 1679:1692 the assignment of structures to lipids extracted from TLC plates because of artifactual oxidation after the plate development 1679:1803 Meanwhile, the findings reported herein reveal a potential pitfall in the assignment of structures to lipids extracted from TLC plates because of artifactual oxidation after the plate development. 24832382 3 39 theme oxidative 457:465 arg1 transformations 505:519 transformations 505:519 transformations at the cleaved double bond positions 505:556 The most common oxidative products, aldehydes, were detected as transformations at the cleaved double bond positions. 24832382 3 39 theme oxidative 457:465 arg1 aldehydes 477:485 aldehydes 477:485 aldehydes 477:485 The most common oxidative products, aldehydes, were detected as transformations at the cleaved double bond positions. 24832382 3 39 theme oxidative 457:465 arg1 products 467:474 The most common oxidative products 441:474 The most common oxidative products 441:474 The most common oxidative products, aldehydes, were detected as transformations at the cleaved double bond positions. 24832382 9 40 theme oxidation 1348:1356 arg1 products 1358:1365 their oxidation products 1342:1365 their oxidation products 1342:1365 Co-localization of the starting lipids and their oxidation products after TLC separation allowed assignment of the native unsaturation sites. 24832382 10 41 theme brain 1522:1526 arg1 extract 1540:1546 a bovine brain total lipid extract 1513:1546 a bovine brain total lipid extract 1513:1546 Phosphatidylserine and N,N-dimethyl phosphatidylethanolamine isomers in a bovine brain total lipid extract were distinguished on the basis of their oxidation products. 24832382 7 42 from group 931:935 arg1 base 954:957 the sphingoid base 940:957 the sphingoid base of sulfatides 940:971 The 3-hydroxyl group in the sphingoid base of sulfatides offered some protection from oxidation for the Δ4,5-double bond, slowing its oxidation rate relative to that of the isolated double bond in the N-linked fatty acyl chain. 24832382 4 43 theme carboxylic 572:581 arg1 acids 583:587 carboxylic acids 572:587 carboxylic acids 572:587 Ozonides and carboxylic acids were generated in certain lipids. 24832382 2 44 theme electrospray 387:398 arg1 spectrometry 422:433 electrospray ionization (ESI) mass spectrometry 387:433 electrospray ionization (ESI) mass spectrometry (MS) 387:438 Lipids were deposited onto various surfaces and the products from their oxidation in ambient air were observed by electrospray ionization (ESI) mass spectrometry (MS). 24832382 2 44 theme electrospray 387:398 arg1 MS 436:437 MS 436:437 MS 436:437 Lipids were deposited onto various surfaces and the products from their oxidation in ambient air were observed by electrospray ionization (ESI) mass spectrometry (MS). 24832382 2 45 theme ambient 358:364 arg1 air 366:368 ambient air 358:368 ambient air 358:368 Lipids were deposited onto various surfaces and the products from their oxidation in ambient air were observed by electrospray ionization (ESI) mass spectrometry (MS). 24832382 1 46 theme carbon-carbon 214:226 arg1 positions 240:248 carbon-carbon double bond positions 214:248 carbon-carbon double bond positions in unsaturated lipids 214:270 A simple, fast approach elucidated carbon-carbon double bond positions in unsaturated lipids. 24832382 7 47 theme double 1098:1103 arg1 bond 1105:1108 the isolated double bond 1085:1108 the isolated double bond in the N-linked fatty acyl chain 1085:1141 The 3-hydroxyl group in the sphingoid base of sulfatides offered some protection from oxidation for the Δ4,5-double bond, slowing its oxidation rate relative to that of the isolated double bond in the N-linked fatty acyl chain. 24832382 11 48 theme potential 1658:1666 arg1 pitfall 1668:1674 a potential pitfall 1656:1674 a potential pitfall in the assignment of structures to lipids extracted from TLC plates because of artifactual oxidation after the plate development 1656:1803 Meanwhile, the findings reported herein reveal a potential pitfall in the assignment of structures to lipids extracted from TLC plates because of artifactual oxidation after the plate development. 24832382 0 49 theme lipid 161:165 arg1 processing 167:176 proper lipid processing 154:176 proper lipid processing 154:176 Surface oxidation under ambient air--not only a fast and economical method to identify double bond positions in unsaturated lipids but also a reminder of proper lipid processing. 24832382 1 50 theme bond 235:238 arg1 positions 240:248 carbon-carbon double bond positions 214:248 carbon-carbon double bond positions in unsaturated lipids 214:270 A simple, fast approach elucidated carbon-carbon double bond positions in unsaturated lipids. 24832382 6 51 theme parallel 875:882 arg1 oxygen 851:856 singlet oxygen 843:856 singlet oxygen 843:856 Since the lipid oxidation was slower in a high concentration of ozone, singlet oxygen appeared to be a parallel oxidant for unsaturated lipids. 24832382 6 51 theme parallel 875:882 arg1 oxidant 884:890 a parallel oxidant 873:890 a parallel oxidant for unsaturated lipids 873:913 Since the lipid oxidation was slower in a high concentration of ozone, singlet oxygen appeared to be a parallel oxidant for unsaturated lipids. 24832382 7 52 theme relative 1065:1072 arg1 rate 1060:1063 its oxidation rate 1046:1063 its oxidation rate relative to that of the isolated double bond in the N-linked fatty acyl chain 1046:1141 The 3-hydroxyl group in the sphingoid base of sulfatides offered some protection from oxidation for the Δ4,5-double bond, slowing its oxidation rate relative to that of the isolated double bond in the N-linked fatty acyl chain. 24832382 6 53 theme lipid 782:786 arg1 oxidation 788:796 the lipid oxidation 778:796 the lipid oxidation 778:796 Since the lipid oxidation was slower in a high concentration of ozone, singlet oxygen appeared to be a parallel oxidant for unsaturated lipids. 24832382 6 53 theme lipid 782:786 arg1 slower 802:807 slower 802:807 slower 802:807 Since the lipid oxidation was slower in a high concentration of ozone, singlet oxygen appeared to be a parallel oxidant for unsaturated lipids. 24832382 9 54 theme unsaturation 1421:1432 arg1 sites 1434:1438 the native unsaturation sites 1410:1438 the native unsaturation sites 1410:1438 Co-localization of the starting lipids and their oxidation products after TLC separation allowed assignment of the native unsaturation sites. 24832382 2 55 from oxidation 345:353 arg1 products 325:332 the products 321:332 the products from their oxidation in ambient air 321:368 Lipids were deposited onto various surfaces and the products from their oxidation in ambient air were observed by electrospray ionization (ESI) mass spectrometry (MS). 24832382 2 55 from oxidation 345:353 arg1 air 366:368 ambient air 358:368 ambient air 358:368 Lipids were deposited onto various surfaces and the products from their oxidation in ambient air were observed by electrospray ionization (ESI) mass spectrometry (MS). 24832382 7 56 theme oxidation 1050:1058 arg1 rate 1060:1063 its oxidation rate 1046:1063 its oxidation rate relative to that of the isolated double bond in the N-linked fatty acyl chain 1046:1141 The 3-hydroxyl group in the sphingoid base of sulfatides offered some protection from oxidation for the Δ4,5-double bond, slowing its oxidation rate relative to that of the isolated double bond in the N-linked fatty acyl chain. 24832382 3 57 theme double 536:541 arg1 positions 548:556 the cleaved double bond positions 524:556 the cleaved double bond positions 524:556 The most common oxidative products, aldehydes, were detected as transformations at the cleaved double bond positions. 24832382 10 58 theme products 1599:1606 arg1 basis 1574:1578 the basis 1570:1578 the basis of their oxidation products 1570:1606 Phosphatidylserine and N,N-dimethyl phosphatidylethanolamine isomers in a bovine brain total lipid extract were distinguished on the basis of their oxidation products. 24832382 0 59 theme unsaturated 112:122 arg1 lipids 124:129 unsaturated lipids 112:129 unsaturated lipids but also a reminder of proper lipid processing 112:176 Surface oxidation under ambient air--not only a fast and economical method to identify double bond positions in unsaturated lipids but also a reminder of proper lipid processing. 24832382 3 60 theme bond 543:546 arg1 positions 548:556 the cleaved double bond positions 524:556 the cleaved double bond positions 524:556 The most common oxidative products, aldehydes, were detected as transformations at the cleaved double bond positions. 24832382 10 61 from Phosphatidylserine 1441:1458 arg1 extract 1540:1546 a bovine brain total lipid extract 1513:1546 a bovine brain total lipid extract 1513:1546 Phosphatidylserine and N,N-dimethyl phosphatidylethanolamine isomers in a bovine brain total lipid extract were distinguished on the basis of their oxidation products. 24832382 8 62 theme powerful 1213:1220 arg1 approach 1222:1229 a powerful approach 1211:1229 a powerful approach to elucidate detailed structural information on biological samples 1211:1296 Direct sampling by thin-layer chromatography (TLC)-ESI-MS provides a powerful approach to elucidate detailed structural information on biological samples. 24832382 8 63 theme thin-layer 1163:1172 arg1 chromatography 1174:1187 thin-layer chromatography 1163:1187 thin-layer chromatography (TLC)-ESI-MS 1163:1200 Direct sampling by thin-layer chromatography (TLC)-ESI-MS provides a powerful approach to elucidate detailed structural information on biological samples. 24832382 8 63 theme thin-layer 1163:1172 arg1 TLC 1190:1192 TLC 1190:1192 TLC 1190:1192 Direct sampling by thin-layer chromatography (TLC)-ESI-MS provides a powerful approach to elucidate detailed structural information on biological samples. 24832382 0 64 from positions 99:107 arg1 lipids 124:129 unsaturated lipids 112:129 unsaturated lipids but also a reminder of proper lipid processing 112:176 Surface oxidation under ambient air--not only a fast and economical method to identify double bond positions in unsaturated lipids but also a reminder of proper lipid processing. 24832382 0 64 from positions 99:107 arg1 reminder 142:149 a reminder 140:149 unsaturated lipids but also a reminder of proper lipid processing 112:176 Surface oxidation under ambient air--not only a fast and economical method to identify double bond positions in unsaturated lipids but also a reminder of proper lipid processing. 24832382 8 65 theme detailed 1244:1251 arg1 information 1264:1274 detailed structural information 1244:1274 detailed structural information on biological samples 1244:1296 Direct sampling by thin-layer chromatography (TLC)-ESI-MS provides a powerful approach to elucidate detailed structural information on biological samples. 24832382 7 66 link N-linked 1117:1124 arg1 chain 1137:1141 the N-linked fatty acyl chain 1113:1141 the N-linked fatty acyl chain 1113:1141 The 3-hydroxyl group in the sphingoid base of sulfatides offered some protection from oxidation for the Δ4,5-double bond, slowing its oxidation rate relative to that of the isolated double bond in the N-linked fatty acyl chain. 24832382 10 67 from isomers 1502:1508 arg1 extract 1540:1546 a bovine brain total lipid extract 1513:1546 a bovine brain total lipid extract 1513:1546 Phosphatidylserine and N,N-dimethyl phosphatidylethanolamine isomers in a bovine brain total lipid extract were distinguished on the basis of their oxidation products. 24832382 0 68 theme economical 57:66 arg1 method 68:73 a fast and economical method 46:73 a fast and economical method to identify double bond positions in unsaturated lipids but also a reminder of proper lipid processing 46:176 Surface oxidation under ambient air--not only a fast and economical method to identify double bond positions in unsaturated lipids but also a reminder of proper lipid processing. 24832382 7 69 theme sulfatides 962:971 arg1 base 954:957 the sphingoid base 940:957 the sphingoid base of sulfatides 940:971 The 3-hydroxyl group in the sphingoid base of sulfatides offered some protection from oxidation for the Δ4,5-double bond, slowing its oxidation rate relative to that of the isolated double bond in the N-linked fatty acyl chain. 24832382 8 70 theme biological 1279:1288 arg1 samples 1290:1296 biological samples 1279:1296 biological samples 1279:1296 Direct sampling by thin-layer chromatography (TLC)-ESI-MS provides a powerful approach to elucidate detailed structural information on biological samples. 24832382 0 71 theme double 87:92 arg1 positions 99:107 double bond positions 87:107 double bond positions in unsaturated lipids but also a reminder of proper lipid processing 87:176 Surface oxidation under ambient air--not only a fast and economical method to identify double bond positions in unsaturated lipids but also a reminder of proper lipid processing. 24832382 8 72 from information 1264:1274 arg1 samples 1290:1296 biological samples 1279:1296 biological samples 1279:1296 Direct sampling by thin-layer chromatography (TLC)-ESI-MS provides a powerful approach to elucidate detailed structural information on biological samples. 24832382 7 73 theme acyl 1132:1135 arg1 chain 1137:1141 the N-linked fatty acyl chain 1113:1141 the N-linked fatty acyl chain 1113:1141 The 3-hydroxyl group in the sphingoid base of sulfatides offered some protection from oxidation for the Δ4,5-double bond, slowing its oxidation rate relative to that of the isolated double bond in the N-linked fatty acyl chain. 24832382 3 74 from positions 548:556 arg1 transformations 505:519 transformations 505:519 transformations at the cleaved double bond positions 505:556 The most common oxidative products, aldehydes, were detected as transformations at the cleaved double bond positions. 24832382 3 74 from positions 548:556 arg1 products 467:474 The most common oxidative products 441:474 The most common oxidative products 441:474 The most common oxidative products, aldehydes, were detected as transformations at the cleaved double bond positions. 24832382 7 75 theme N-linked 1117:1124 arg1 chain 1137:1141 the N-linked fatty acyl chain 1113:1141 the N-linked fatty acyl chain 1113:1141 The 3-hydroxyl group in the sphingoid base of sulfatides offered some protection from oxidation for the Δ4,5-double bond, slowing its oxidation rate relative to that of the isolated double bond in the N-linked fatty acyl chain. 24832382 9 76 theme lipids 1331:1336 arg1 Co-localization 1299:1313 Co-localization 1299:1313 Co-localization of the starting lipids and their oxidation products after TLC separation 1299:1386 Co-localization of the starting lipids and their oxidation products after TLC separation allowed assignment of the native unsaturation sites. 24832382 10 77 theme phosphatidylethanolamine 1477:1500 arg1 isomers 1502:1508 N,N-dimethyl phosphatidylethanolamine isomers 1464:1508 N,N-dimethyl phosphatidylethanolamine isomers 1464:1508 Phosphatidylserine and N,N-dimethyl phosphatidylethanolamine isomers in a bovine brain total lipid extract were distinguished on the basis of their oxidation products. 24832382 0 78 theme bond 94:97 arg1 positions 99:107 double bond positions 87:107 double bond positions in unsaturated lipids but also a reminder of proper lipid processing 87:176 Surface oxidation under ambient air--not only a fast and economical method to identify double bond positions in unsaturated lipids but also a reminder of proper lipid processing. 24832382 0 79 theme fast 48:51 arg1 method 68:73 a fast and economical method 46:73 a fast and economical method to identify double bond positions in unsaturated lipids but also a reminder of proper lipid processing 46:176 Surface oxidation under ambient air--not only a fast and economical method to identify double bond positions in unsaturated lipids but also a reminder of proper lipid processing. 24832382 10 80 theme total 1528:1532 arg1 extract 1540:1546 a bovine brain total lipid extract 1513:1546 a bovine brain total lipid extract 1513:1546 Phosphatidylserine and N,N-dimethyl phosphatidylethanolamine isomers in a bovine brain total lipid extract were distinguished on the basis of their oxidation products. 24832382 11 81 theme TLC 1733:1735 arg1 plates 1737:1742 TLC plates 1733:1742 TLC plates 1733:1742 Meanwhile, the findings reported herein reveal a potential pitfall in the assignment of structures to lipids extracted from TLC plates because of artifactual oxidation after the plate development. 24832382 9 82 theme products 1358:1365 arg1 Co-localization 1299:1313 Co-localization 1299:1313 Co-localization of the starting lipids and their oxidation products after TLC separation 1299:1386 Co-localization of the starting lipids and their oxidation products after TLC separation allowed assignment of the native unsaturation sites. 24832382 6 83 theme high 814:817 arg1 concentration 819:831 a high concentration 812:831 a high concentration of ozone 812:840 Since the lipid oxidation was slower in a high concentration of ozone, singlet oxygen appeared to be a parallel oxidant for unsaturated lipids. 24832382 7 84 from oxidation 1002:1010 arg1 protection 986:995 some protection 981:995 some protection from oxidation for the Δ4,5-double bond 981:1035 The 3-hydroxyl group in the sphingoid base of sulfatides offered some protection from oxidation for the Δ4,5-double bond, slowing its oxidation rate relative to that of the isolated double bond in the N-linked fatty acyl chain. 24832382 10 85 theme bovine 1515:1520 arg1 extract 1540:1546 a bovine brain total lipid extract 1513:1546 a bovine brain total lipid extract 1513:1546 Phosphatidylserine and N,N-dimethyl phosphatidylethanolamine isomers in a bovine brain total lipid extract were distinguished on the basis of their oxidation products. 24832382 3 86 theme common 450:455 arg1 transformations 505:519 transformations 505:519 transformations at the cleaved double bond positions 505:556 The most common oxidative products, aldehydes, were detected as transformations at the cleaved double bond positions. 24832382 3 86 theme common 450:455 arg1 aldehydes 477:485 aldehydes 477:485 aldehydes 477:485 The most common oxidative products, aldehydes, were detected as transformations at the cleaved double bond positions. 24832382 3 86 theme common 450:455 arg1 products 467:474 The most common oxidative products 441:474 The most common oxidative products 441:474 The most common oxidative products, aldehydes, were detected as transformations at the cleaved double bond positions. 24832382 9 87 theme TLC 1373:1375 arg1 separation 1377:1386 TLC separation 1373:1386 TLC separation 1373:1386 Co-localization of the starting lipids and their oxidation products after TLC separation allowed assignment of the native unsaturation sites. 24832382 1 88 dep simple 181:186 arg1 fast 189:192 fast 189:192 fast 189:192 A simple, fast approach elucidated carbon-carbon double bond positions in unsaturated lipids. 24832382 1 89 theme double 228:233 arg1 positions 240:248 carbon-carbon double bond positions 214:248 carbon-carbon double bond positions in unsaturated lipids 214:270 A simple, fast approach elucidated carbon-carbon double bond positions in unsaturated lipids. 24561590 3 0 from lack 745:748 arg1 gene 795:798 the wild-type lysostaphin gene 769:798 the wild-type lysostaphin gene 769:798 While Pichia pastoris is widely used for high-level production of recombinant proteins, there are two major barriers to the production of lysostaphin in this industrially relevant host: lack of expression from the wild-type lysostaphin gene and aberrant glycosylation of the wild-type protein sequence. 24561590 5 1 theme optimized 1167:1175 arg1 variants 1189:1196 The optimized lysostaphin variants 1163:1196 The optimized lysostaphin variants 1163:1196 The optimized lysostaphin variants could be produced at approximately 500 mg/liter in a small-scale bioreactor, and 50% of that material could be recovered at high purity with a simple 2-step purification. 24561590 1 2 theme therapeutic 166:176 arg1 agent 178:182 a promising therapeutic agent 154:182 a promising therapeutic agent for the treatment of staphylococcal infections 154:229 Lysostaphin represents a promising therapeutic agent for the treatment of staphylococcal infections, in particular those of methicillin-resistant Staphylococcus aureus (MRSA). 24561590 0 3 theme active 74:79 arg1 lysostaphin 99:109 fully active and aglycosylated lysostaphin 68:109 fully active and aglycosylated lysostaphin 68:109 Gene and protein sequence optimization for high-level production of fully active and aglycosylated lysostaphin in Pichia pastoris. 24561590 3 4 gly glycosylation 813:825 arg1 sequence 852:859 the wild-type protein sequence 830:859 the wild-type protein sequence 830:859 While Pichia pastoris is widely used for high-level production of recombinant proteins, there are two major barriers to the production of lysostaphin in this industrially relevant host: lack of expression from the wild-type lysostaphin gene and aberrant glycosylation of the wild-type protein sequence. 24561590 3 4 gly glycosylation 813:825 arg1 expression 753:762 expression 753:762 expression from the wild-type lysostaphin gene 753:798 While Pichia pastoris is widely used for high-level production of recombinant proteins, there are two major barriers to the production of lysostaphin in this industrially relevant host: lack of expression from the wild-type lysostaphin gene and aberrant glycosylation of the wild-type protein sequence. 24561590 3 5 from glycosylation 813:825 arg1 gene 795:798 the wild-type lysostaphin gene 769:798 the wild-type lysostaphin gene 769:798 While Pichia pastoris is widely used for high-level production of recombinant proteins, there are two major barriers to the production of lysostaphin in this industrially relevant host: lack of expression from the wild-type lysostaphin gene and aberrant glycosylation of the wild-type protein sequence. 24561590 6 6 theme novel 1397:1401 arg1 system 1425:1430 this novel high-level expression system 1392:1430 this novel high-level expression system 1392:1430 It is anticipated that this novel high-level expression system will bring down one of the major barriers to future development of biomedical, veterinary, and research applications of lysostaphin and its engineered variants. 24561590 2 7 theme various 375:381 arg1 limitations 383:393 various limitations 375:393 various limitations 375:393 However, conventional expression systems for the enzyme suffer from various limitations, and there remains a need for an efficient and cost-effective production process to facilitate clinical translation and the development of nonmedical applications. 24561590 6 8 theme biomedical 1499:1508 arg1 applications 1536:1547 biomedical, veterinary, and research applications 1499:1547 biomedical, veterinary, and research applications of lysostaphin and its engineered variants 1499:1590 It is anticipated that this novel high-level expression system will bring down one of the major barriers to future development of biomedical, veterinary, and research applications of lysostaphin and its engineered variants. 24561590 0 9 theme lysostaphin 99:109 arg1 production 54:63 high-level production 43:63 high-level production of fully active and aglycosylated lysostaphin in Pichia pastoris 43:128 Gene and protein sequence optimization for high-level production of fully active and aglycosylated lysostaphin in Pichia pastoris. 24561590 4 10 theme improved 932:939 arg1 usage 947:951 improved codon usage 932:951 improved codon usage 932:951 The first barrier can be overcome with a synthetic gene incorporating improved codon usage and balanced A+T/G+C content, and the second barrier can be overcome by disrupting an N-linked glycosylation sequon using a broadened choice of mutations that yield aglyscosylated and fully active lysostaphin. 24561590 3 11 theme high-level 600:609 arg1 production 611:620 high-level production 600:620 high-level production of recombinant proteins 600:644 While Pichia pastoris is widely used for high-level production of recombinant proteins, there are two major barriers to the production of lysostaphin in this industrially relevant host: lack of expression from the wild-type lysostaphin gene and aberrant glycosylation of the wild-type protein sequence. 24561590 6 12 theme high-level 1403:1412 arg1 system 1425:1430 this novel high-level expression system 1392:1430 this novel high-level expression system 1392:1430 It is anticipated that this novel high-level expression system will bring down one of the major barriers to future development of biomedical, veterinary, and research applications of lysostaphin and its engineered variants. 24561590 0 13 theme aglycosylated 85:97 arg1 lysostaphin 99:109 fully active and aglycosylated lysostaphin 68:109 fully active and aglycosylated lysostaphin 68:109 Gene and protein sequence optimization for high-level production of fully active and aglycosylated lysostaphin in Pichia pastoris. 24561590 0 14 from production 54:63 arg1 pastoris 121:128 Pichia pastoris 114:128 Pichia pastoris 114:128 Gene and protein sequence optimization for high-level production of fully active and aglycosylated lysostaphin in Pichia pastoris. 24561590 5 15 theme material 1291:1298 arg1 % 1281:1281 50% 1279:1281 50% of that material 1279:1298 The optimized lysostaphin variants could be produced at approximately 500 mg/liter in a small-scale bioreactor, and 50% of that material could be recovered at high purity with a simple 2-step purification. 24561590 5 15 theme material 1291:1298 arg1 material 1291:1298 that material 1286:1298 that material 1286:1298 The optimized lysostaphin variants could be produced at approximately 500 mg/liter in a small-scale bioreactor, and 50% of that material could be recovered at high purity with a simple 2-step purification. 24561590 6 16 theme engineered 1572:1581 arg1 variants 1583:1590 its engineered variants 1568:1590 its engineered variants 1568:1590 It is anticipated that this novel high-level expression system will bring down one of the major barriers to future development of biomedical, veterinary, and research applications of lysostaphin and its engineered variants. 24561590 0 17 theme Pichia 114:119 arg1 pastoris 121:128 Pichia pastoris 114:128 Pichia pastoris 114:128 Gene and protein sequence optimization for high-level production of fully active and aglycosylated lysostaphin in Pichia pastoris. 24561590 2 18 theme efficient 428:436 arg1 process 468:474 an efficient and cost-effective production process 425:474 an efficient and cost-effective production process 425:474 However, conventional expression systems for the enzyme suffer from various limitations, and there remains a need for an efficient and cost-effective production process to facilitate clinical translation and the development of nonmedical applications. 24561590 2 19 theme applications 545:556 arg1 translation 499:509 clinical translation 490:509 clinical translation 490:509 However, conventional expression systems for the enzyme suffer from various limitations, and there remains a need for an efficient and cost-effective production process to facilitate clinical translation and the development of nonmedical applications. 24561590 2 19 theme applications 545:556 arg1 development 519:529 the development 515:529 the development of nonmedical applications 515:556 However, conventional expression systems for the enzyme suffer from various limitations, and there remains a need for an efficient and cost-effective production process to facilitate clinical translation and the development of nonmedical applications. 24561590 6 20 theme of 1452:1453 arg1 barriers 1465:1472 down one of the major barriers 1443:1472 down one of the major barriers 1443:1472 It is anticipated that this novel high-level expression system will bring down one of the major barriers to future development of biomedical, veterinary, and research applications of lysostaphin and its engineered variants. 24561590 6 21 theme major 1459:1463 arg1 barriers 1465:1472 down one of the major barriers 1443:1472 down one of the major barriers 1443:1472 It is anticipated that this novel high-level expression system will bring down one of the major barriers to future development of biomedical, veterinary, and research applications of lysostaphin and its engineered variants. 24561590 6 22 theme future 1477:1482 arg1 development 1484:1494 future development 1477:1494 future development of biomedical, veterinary, and research applications of lysostaphin and its engineered variants 1477:1590 It is anticipated that this novel high-level expression system will bring down one of the major barriers to future development of biomedical, veterinary, and research applications of lysostaphin and its engineered variants. 24561590 6 23 theme variants 1583:1590 arg1 applications 1536:1547 biomedical, veterinary, and research applications 1499:1547 biomedical, veterinary, and research applications of lysostaphin and its engineered variants 1499:1590 It is anticipated that this novel high-level expression system will bring down one of the major barriers to future development of biomedical, veterinary, and research applications of lysostaphin and its engineered variants. 24561590 3 24 from production 683:692 arg1 host 739:742 this industrially relevant host 712:742 this industrially relevant host 712:742 While Pichia pastoris is widely used for high-level production of recombinant proteins, there are two major barriers to the production of lysostaphin in this industrially relevant host: lack of expression from the wild-type lysostaphin gene and aberrant glycosylation of the wild-type protein sequence. 24561590 3 25 theme expression 753:762 arg1 glycosylation 813:825 aberrant glycosylation 804:825 aberrant glycosylation of the wild-type protein sequence 804:859 While Pichia pastoris is widely used for high-level production of recombinant proteins, there are two major barriers to the production of lysostaphin in this industrially relevant host: lack of expression from the wild-type lysostaphin gene and aberrant glycosylation of the wild-type protein sequence. 24561590 3 25 theme expression 753:762 arg1 lack 745:748 lack 745:748 lack of expression from the wild-type lysostaphin gene 745:798 While Pichia pastoris is widely used for high-level production of recombinant proteins, there are two major barriers to the production of lysostaphin in this industrially relevant host: lack of expression from the wild-type lysostaphin gene and aberrant glycosylation of the wild-type protein sequence. 24561590 3 26 from gene 795:798 arg1 expression 753:762 expression 753:762 expression from the wild-type lysostaphin gene 753:798 While Pichia pastoris is widely used for high-level production of recombinant proteins, there are two major barriers to the production of lysostaphin in this industrially relevant host: lack of expression from the wild-type lysostaphin gene and aberrant glycosylation of the wild-type protein sequence. 24561590 3 26 from gene 795:798 arg1 lack 745:748 lack 745:748 lack of expression from the wild-type lysostaphin gene 745:798 While Pichia pastoris is widely used for high-level production of recombinant proteins, there are two major barriers to the production of lysostaphin in this industrially relevant host: lack of expression from the wild-type lysostaphin gene and aberrant glycosylation of the wild-type protein sequence. 24561590 3 26 from gene 795:798 arg1 glycosylation 813:825 aberrant glycosylation 804:825 aberrant glycosylation of the wild-type protein sequence 804:859 While Pichia pastoris is widely used for high-level production of recombinant proteins, there are two major barriers to the production of lysostaphin in this industrially relevant host: lack of expression from the wild-type lysostaphin gene and aberrant glycosylation of the wild-type protein sequence. 24561590 6 27 theme down 1443:1446 arg1 barriers 1465:1472 down one of the major barriers 1443:1472 down one of the major barriers 1443:1472 It is anticipated that this novel high-level expression system will bring down one of the major barriers to future development of biomedical, veterinary, and research applications of lysostaphin and its engineered variants. 24561590 0 28 gly aglycosylated 85:97 arg1 lysostaphin 99:109 fully active and aglycosylated lysostaphin 68:109 fully active and aglycosylated lysostaphin 68:109 Gene and protein sequence optimization for high-level production of fully active and aglycosylated lysostaphin in Pichia pastoris. 24561590 4 29 link N-linked 1039:1046 arg1 sequon 1062:1067 an N-linked glycosylation sequon 1036:1067 an N-linked glycosylation sequon using a broadened choice of mutations that yield aglyscosylated and fully active lysostaphin 1036:1160 The first barrier can be overcome with a synthetic gene incorporating improved codon usage and balanced A+T/G+C content, and the second barrier can be overcome by disrupting an N-linked glycosylation sequon using a broadened choice of mutations that yield aglyscosylated and fully active lysostaphin. 24561590 3 30 used used 591:594 arg2 pastoris 572:579 Pichia pastoris 565:579 Pichia pastoris 565:579 While Pichia pastoris is widely used for high-level production of recombinant proteins, there are two major barriers to the production of lysostaphin in this industrially relevant host: lack of expression from the wild-type lysostaphin gene and aberrant glycosylation of the wild-type protein sequence. 24561590 3 31 theme relevant 730:737 arg1 host 739:742 this industrially relevant host 712:742 this industrially relevant host 712:742 While Pichia pastoris is widely used for high-level production of recombinant proteins, there are two major barriers to the production of lysostaphin in this industrially relevant host: lack of expression from the wild-type lysostaphin gene and aberrant glycosylation of the wild-type protein sequence. 24561590 5 32 theme simple 1341:1346 arg1 purification 1355:1366 a simple 2-step purification 1339:1366 a simple 2-step purification 1339:1366 The optimized lysostaphin variants could be produced at approximately 500 mg/liter in a small-scale bioreactor, and 50% of that material could be recovered at high purity with a simple 2-step purification. 24561590 4 33 theme synthetic 903:911 arg1 gene 913:916 a synthetic gene 901:916 a synthetic gene incorporating improved codon usage and balanced A+T/G+C content 901:980 The first barrier can be overcome with a synthetic gene incorporating improved codon usage and balanced A+T/G+C content, and the second barrier can be overcome by disrupting an N-linked glycosylation sequon using a broadened choice of mutations that yield aglyscosylated and fully active lysostaphin. 24561590 2 34 theme production 457:466 arg1 process 468:474 an efficient and cost-effective production process 425:474 an efficient and cost-effective production process 425:474 However, conventional expression systems for the enzyme suffer from various limitations, and there remains a need for an efficient and cost-effective production process to facilitate clinical translation and the development of nonmedical applications. 24561590 2 35 theme expression 329:338 arg1 systems 340:346 conventional expression systems 316:346 conventional expression systems for the enzyme 316:361 However, conventional expression systems for the enzyme suffer from various limitations, and there remains a need for an efficient and cost-effective production process to facilitate clinical translation and the development of nonmedical applications. 24561590 5 36 theme 2-step 1348:1353 arg1 purification 1355:1366 a simple 2-step purification 1339:1366 a simple 2-step purification 1339:1366 The optimized lysostaphin variants could be produced at approximately 500 mg/liter in a small-scale bioreactor, and 50% of that material could be recovered at high purity with a simple 2-step purification. 24561590 1 37 theme staphylococcal 205:218 arg1 infections 220:229 staphylococcal infections 205:229 staphylococcal infections 205:229 Lysostaphin represents a promising therapeutic agent for the treatment of staphylococcal infections, in particular those of methicillin-resistant Staphylococcus aureus (MRSA). 24561590 2 38 theme cost-effective 442:455 arg1 process 468:474 an efficient and cost-effective production process 425:474 an efficient and cost-effective production process 425:474 However, conventional expression systems for the enzyme suffer from various limitations, and there remains a need for an efficient and cost-effective production process to facilitate clinical translation and the development of nonmedical applications. 24561590 3 39 theme wild-type 773:781 arg1 gene 795:798 the wild-type lysostaphin gene 769:798 the wild-type lysostaphin gene 769:798 While Pichia pastoris is widely used for high-level production of recombinant proteins, there are two major barriers to the production of lysostaphin in this industrially relevant host: lack of expression from the wild-type lysostaphin gene and aberrant glycosylation of the wild-type protein sequence. 24561590 4 40 theme A+T/G+C 966:972 arg1 content 974:980 balanced A+T/G+C content 957:980 balanced A+T/G+C content 957:980 The first barrier can be overcome with a synthetic gene incorporating improved codon usage and balanced A+T/G+C content, and the second barrier can be overcome by disrupting an N-linked glycosylation sequon using a broadened choice of mutations that yield aglyscosylated and fully active lysostaphin. 24561590 2 41 theme conventional 316:327 arg1 systems 340:346 conventional expression systems 316:346 conventional expression systems for the enzyme 316:361 However, conventional expression systems for the enzyme suffer from various limitations, and there remains a need for an efficient and cost-effective production process to facilitate clinical translation and the development of nonmedical applications. 24561590 6 42 theme lysostaphin 1552:1562 arg1 applications 1536:1547 biomedical, veterinary, and research applications 1499:1547 biomedical, veterinary, and research applications of lysostaphin and its engineered variants 1499:1590 It is anticipated that this novel high-level expression system will bring down one of the major barriers to future development of biomedical, veterinary, and research applications of lysostaphin and its engineered variants. 24561590 1 43 theme infections 220:229 arg1 treatment 192:200 the treatment 188:200 the treatment of staphylococcal infections 188:229 Lysostaphin represents a promising therapeutic agent for the treatment of staphylococcal infections, in particular those of methicillin-resistant Staphylococcus aureus (MRSA). 24561590 4 44 theme N-linked 1039:1046 arg1 sequon 1062:1067 an N-linked glycosylation sequon 1036:1067 an N-linked glycosylation sequon using a broadened choice of mutations that yield aglyscosylated and fully active lysostaphin 1036:1160 The first barrier can be overcome with a synthetic gene incorporating improved codon usage and balanced A+T/G+C content, and the second barrier can be overcome by disrupting an N-linked glycosylation sequon using a broadened choice of mutations that yield aglyscosylated and fully active lysostaphin. 24561590 3 45 theme lysostaphin 783:793 arg1 gene 795:798 the wild-type lysostaphin gene 769:798 the wild-type lysostaphin gene 769:798 While Pichia pastoris is widely used for high-level production of recombinant proteins, there are two major barriers to the production of lysostaphin in this industrially relevant host: lack of expression from the wild-type lysostaphin gene and aberrant glycosylation of the wild-type protein sequence. 24561590 4 46 theme first 866:870 arg1 barrier 872:878 The first barrier 862:878 The first barrier 862:878 The first barrier can be overcome with a synthetic gene incorporating improved codon usage and balanced A+T/G+C content, and the second barrier can be overcome by disrupting an N-linked glycosylation sequon using a broadened choice of mutations that yield aglyscosylated and fully active lysostaphin. 24561590 6 47 theme applications 1536:1547 arg1 development 1484:1494 future development 1477:1494 future development of biomedical, veterinary, and research applications of lysostaphin and its engineered variants 1477:1590 It is anticipated that this novel high-level expression system will bring down one of the major barriers to future development of biomedical, veterinary, and research applications of lysostaphin and its engineered variants. 24561590 4 48 theme glycosylation 1048:1060 arg1 sequon 1062:1067 an N-linked glycosylation sequon 1036:1067 an N-linked glycosylation sequon using a broadened choice of mutations that yield aglyscosylated and fully active lysostaphin 1036:1160 The first barrier can be overcome with a synthetic gene incorporating improved codon usage and balanced A+T/G+C content, and the second barrier can be overcome by disrupting an N-linked glycosylation sequon using a broadened choice of mutations that yield aglyscosylated and fully active lysostaphin. 24561590 1 49 dep particular 235:244 arg1 those 246:250 those 246:250 those 246:250 Lysostaphin represents a promising therapeutic agent for the treatment of staphylococcal infections, in particular those of methicillin-resistant Staphylococcus aureus (MRSA). 24561590 0 50 theme sequence 17:24 arg1 optimization 26:37 protein sequence optimization 9:37 protein sequence optimization 9:37 Gene and protein sequence optimization for high-level production of fully active and aglycosylated lysostaphin in Pichia pastoris. 24561590 5 51 theme small-scale 1251:1261 arg1 bioreactor 1263:1272 a small-scale bioreactor 1249:1272 a small-scale bioreactor 1249:1272 The optimized lysostaphin variants could be produced at approximately 500 mg/liter in a small-scale bioreactor, and 50% of that material could be recovered at high purity with a simple 2-step purification. 24561590 2 52 theme clinical 490:497 arg1 translation 499:509 clinical translation 490:509 clinical translation 490:509 However, conventional expression systems for the enzyme suffer from various limitations, and there remains a need for an efficient and cost-effective production process to facilitate clinical translation and the development of nonmedical applications. 24561590 4 53 theme second 991:996 arg1 barrier 998:1004 the second barrier 987:1004 the second barrier 987:1004 The first barrier can be overcome with a synthetic gene incorporating improved codon usage and balanced A+T/G+C content, and the second barrier can be overcome by disrupting an N-linked glycosylation sequon using a broadened choice of mutations that yield aglyscosylated and fully active lysostaphin. 24561590 6 54 theme expression 1414:1423 arg1 system 1425:1430 this novel high-level expression system 1392:1430 this novel high-level expression system 1392:1430 It is anticipated that this novel high-level expression system will bring down one of the major barriers to future development of biomedical, veterinary, and research applications of lysostaphin and its engineered variants. 24561590 3 55 theme recombinant 625:635 arg1 proteins 637:644 recombinant proteins 625:644 recombinant proteins 625:644 While Pichia pastoris is widely used for high-level production of recombinant proteins, there are two major barriers to the production of lysostaphin in this industrially relevant host: lack of expression from the wild-type lysostaphin gene and aberrant glycosylation of the wild-type protein sequence. 24561590 0 56 theme high-level 43:52 arg1 production 54:63 high-level production 43:63 high-level production of fully active and aglycosylated lysostaphin in Pichia pastoris 43:128 Gene and protein sequence optimization for high-level production of fully active and aglycosylated lysostaphin in Pichia pastoris. 24561590 3 57 theme aberrant 804:811 arg1 glycosylation 813:825 aberrant glycosylation 804:825 aberrant glycosylation of the wild-type protein sequence 804:859 While Pichia pastoris is widely used for high-level production of recombinant proteins, there are two major barriers to the production of lysostaphin in this industrially relevant host: lack of expression from the wild-type lysostaphin gene and aberrant glycosylation of the wild-type protein sequence. 24561590 4 58 theme codon 941:945 arg1 usage 947:951 improved codon usage 932:951 improved codon usage 932:951 The first barrier can be overcome with a synthetic gene incorporating improved codon usage and balanced A+T/G+C content, and the second barrier can be overcome by disrupting an N-linked glycosylation sequon using a broadened choice of mutations that yield aglyscosylated and fully active lysostaphin. 24561590 3 59 theme proteins 637:644 arg1 production 611:620 high-level production 600:620 high-level production of recombinant proteins 600:644 While Pichia pastoris is widely used for high-level production of recombinant proteins, there are two major barriers to the production of lysostaphin in this industrially relevant host: lack of expression from the wild-type lysostaphin gene and aberrant glycosylation of the wild-type protein sequence. 24561590 5 60 theme high 1322:1325 arg1 purity 1327:1332 high purity 1322:1332 high purity 1322:1332 The optimized lysostaphin variants could be produced at approximately 500 mg/liter in a small-scale bioreactor, and 50% of that material could be recovered at high purity with a simple 2-step purification. 24561590 4 61 theme balanced 957:964 arg1 content 974:980 balanced A+T/G+C content 957:980 balanced A+T/G+C content 957:980 The first barrier can be overcome with a synthetic gene incorporating improved codon usage and balanced A+T/G+C content, and the second barrier can be overcome by disrupting an N-linked glycosylation sequon using a broadened choice of mutations that yield aglyscosylated and fully active lysostaphin. 24561590 4 62 theme broadened 1077:1085 arg1 choice 1087:1092 a broadened choice 1075:1092 a broadened choice of mutations that yield aglyscosylated and fully active lysostaphin 1075:1160 The first barrier can be overcome with a synthetic gene incorporating improved codon usage and balanced A+T/G+C content, and the second barrier can be overcome by disrupting an N-linked glycosylation sequon using a broadened choice of mutations that yield aglyscosylated and fully active lysostaphin. 24561590 3 63 theme major 661:665 arg1 barriers 667:674 two major barriers 657:674 two major barriers to the production of lysostaphin in this industrially relevant host 657:742 While Pichia pastoris is widely used for high-level production of recombinant proteins, there are two major barriers to the production of lysostaphin in this industrially relevant host: lack of expression from the wild-type lysostaphin gene and aberrant glycosylation of the wild-type protein sequence. 24561590 4 64 theme aglyscosylated 1118:1131 arg1 lysostaphin 1150:1160 aglyscosylated and fully active lysostaphin 1118:1160 aglyscosylated and fully active lysostaphin 1118:1160 The first barrier can be overcome with a synthetic gene incorporating improved codon usage and balanced A+T/G+C content, and the second barrier can be overcome by disrupting an N-linked glycosylation sequon using a broadened choice of mutations that yield aglyscosylated and fully active lysostaphin. 24561590 3 65 theme sequence 852:859 arg1 glycosylation 813:825 aberrant glycosylation 804:825 aberrant glycosylation of the wild-type protein sequence 804:859 While Pichia pastoris is widely used for high-level production of recombinant proteins, there are two major barriers to the production of lysostaphin in this industrially relevant host: lack of expression from the wild-type lysostaphin gene and aberrant glycosylation of the wild-type protein sequence. 24561590 3 65 theme sequence 852:859 arg1 lack 745:748 lack 745:748 lack of expression from the wild-type lysostaphin gene 745:798 While Pichia pastoris is widely used for high-level production of recombinant proteins, there are two major barriers to the production of lysostaphin in this industrially relevant host: lack of expression from the wild-type lysostaphin gene and aberrant glycosylation of the wild-type protein sequence. 24561590 3 66 theme lysostaphin 697:707 arg1 production 683:692 the production 679:692 the production of lysostaphin in this industrially relevant host 679:742 While Pichia pastoris is widely used for high-level production of recombinant proteins, there are two major barriers to the production of lysostaphin in this industrially relevant host: lack of expression from the wild-type lysostaphin gene and aberrant glycosylation of the wild-type protein sequence. 24561590 4 67 theme active 1143:1148 arg1 lysostaphin 1150:1160 aglyscosylated and fully active lysostaphin 1118:1160 aglyscosylated and fully active lysostaphin 1118:1160 The first barrier can be overcome with a synthetic gene incorporating improved codon usage and balanced A+T/G+C content, and the second barrier can be overcome by disrupting an N-linked glycosylation sequon using a broadened choice of mutations that yield aglyscosylated and fully active lysostaphin. 24561590 2 68 theme nonmedical 534:543 arg1 applications 545:556 nonmedical applications 534:556 nonmedical applications 534:556 However, conventional expression systems for the enzyme suffer from various limitations, and there remains a need for an efficient and cost-effective production process to facilitate clinical translation and the development of nonmedical applications. 24561590 4 69 gly glycosylation 1048:1060 arg2 sequon 1062:1067 an N-linked glycosylation sequon 1036:1067 an N-linked glycosylation sequon using a broadened choice of mutations that yield aglyscosylated and fully active lysostaphin 1036:1160 The first barrier can be overcome with a synthetic gene incorporating improved codon usage and balanced A+T/G+C content, and the second barrier can be overcome by disrupting an N-linked glycosylation sequon using a broadened choice of mutations that yield aglyscosylated and fully active lysostaphin. 24561590 3 70 dep are 653:655 arg1 glycosylation 813:825 aberrant glycosylation 804:825 aberrant glycosylation of the wild-type protein sequence 804:859 While Pichia pastoris is widely used for high-level production of recombinant proteins, there are two major barriers to the production of lysostaphin in this industrially relevant host: lack of expression from the wild-type lysostaphin gene and aberrant glycosylation of the wild-type protein sequence. 24561590 3 70 dep are 653:655 arg1 lack 745:748 lack 745:748 lack of expression from the wild-type lysostaphin gene 745:798 While Pichia pastoris is widely used for high-level production of recombinant proteins, there are two major barriers to the production of lysostaphin in this industrially relevant host: lack of expression from the wild-type lysostaphin gene and aberrant glycosylation of the wild-type protein sequence. 24561590 6 71 theme research 1527:1534 arg1 applications 1536:1547 biomedical, veterinary, and research applications 1499:1547 biomedical, veterinary, and research applications of lysostaphin and its engineered variants 1499:1590 It is anticipated that this novel high-level expression system will bring down one of the major barriers to future development of biomedical, veterinary, and research applications of lysostaphin and its engineered variants. 24561590 3 72 theme wild-type 834:842 arg1 sequence 852:859 the wild-type protein sequence 830:859 the wild-type protein sequence 830:859 While Pichia pastoris is widely used for high-level production of recombinant proteins, there are two major barriers to the production of lysostaphin in this industrially relevant host: lack of expression from the wild-type lysostaphin gene and aberrant glycosylation of the wild-type protein sequence. 24561590 6 73 theme veterinary 1511:1520 arg1 applications 1536:1547 biomedical, veterinary, and research applications 1499:1547 biomedical, veterinary, and research applications of lysostaphin and its engineered variants 1499:1590 It is anticipated that this novel high-level expression system will bring down one of the major barriers to future development of biomedical, veterinary, and research applications of lysostaphin and its engineered variants. 24561590 5 74 theme lysostaphin 1177:1187 arg1 variants 1189:1196 The optimized lysostaphin variants 1163:1196 The optimized lysostaphin variants 1163:1196 The optimized lysostaphin variants could be produced at approximately 500 mg/liter in a small-scale bioreactor, and 50% of that material could be recovered at high purity with a simple 2-step purification. 24561590 0 75 theme protein 9:15 arg1 optimization 26:37 protein sequence optimization 9:37 protein sequence optimization 9:37 Gene and protein sequence optimization for high-level production of fully active and aglycosylated lysostaphin in Pichia pastoris. 24561590 1 76 theme promising 156:164 arg1 agent 178:182 a promising therapeutic agent 154:182 a promising therapeutic agent for the treatment of staphylococcal infections 154:229 Lysostaphin represents a promising therapeutic agent for the treatment of staphylococcal infections, in particular those of methicillin-resistant Staphylococcus aureus (MRSA). 24561590 4 77 theme mutations 1097:1105 arg1 choice 1087:1092 a broadened choice 1075:1092 a broadened choice of mutations that yield aglyscosylated and fully active lysostaphin 1075:1160 The first barrier can be overcome with a synthetic gene incorporating improved codon usage and balanced A+T/G+C content, and the second barrier can be overcome by disrupting an N-linked glycosylation sequon using a broadened choice of mutations that yield aglyscosylated and fully active lysostaphin. 24561590 3 78 theme protein 844:850 arg1 sequence 852:859 the wild-type protein sequence 830:859 the wild-type protein sequence 830:859 While Pichia pastoris is widely used for high-level production of recombinant proteins, there are two major barriers to the production of lysostaphin in this industrially relevant host: lack of expression from the wild-type lysostaphin gene and aberrant glycosylation of the wild-type protein sequence. 24365146 3 0 theme threonine 328:336 arg1 substitution 338:349 Simultaneous threonine substitution 315:349 Simultaneous threonine substitution for these residues 315:368 Simultaneous threonine substitution for these residues completely abrogates the glycosylation, but does not prevent Nox1 from forming a heterodimer with p22(phox), trafficking to the cell surface, or producing superoxide. 24365146 1 1 theme NADPH 164:168 arg1 oxidases 170:177 superoxide-producing NADPH oxidases 143:177 superoxide-producing NADPH oxidases 143:177 Nox1 is a membrane-integrated protein that belongs to the Nox family of superoxide-producing NADPH oxidases. 24365146 6 2 from Pro-156 1013:1019 arg1 mutation 1037:1044 a mutation 1035:1044 a mutation leading to a defective interaction with the Nox1-activating protein Noxo1 1035:1118 Superoxide production by unglycosylated Nox1 is largely dependent on p22(phox), which is abrogated by glutamine substitution for Pro-156 in p22(phox), a mutation leading to a defective interaction with the Nox1-activating protein Noxo1. 24365146 6 2 from Pro-156 1013:1019 arg1 phox 1028:1031 phox 1028:1031 phox 1028:1031 Superoxide production by unglycosylated Nox1 is largely dependent on p22(phox), which is abrogated by glutamine substitution for Pro-156 in p22(phox), a mutation leading to a defective interaction with the Nox1-activating protein Noxo1. 24365146 6 2 from Pro-156 1013:1019 arg1 p22 1024:1026 p22 1024:1026 p22(phox) 1024:1032 Superoxide production by unglycosylated Nox1 is largely dependent on p22(phox), which is abrogated by glutamine substitution for Pro-156 in p22(phox), a mutation leading to a defective interaction with the Nox1-activating protein Noxo1. 24365146 1 3 theme oxidases 170:177 arg1 family 133:138 the Nox family 125:138 the Nox family of superoxide-producing NADPH oxidases 125:177 Nox1 is a membrane-integrated protein that belongs to the Nox family of superoxide-producing NADPH oxidases. 24365146 6 4 gly unglycosylated 909:922 arg1 Nox1 924:927 unglycosylated Nox1 909:927 unglycosylated Nox1 909:927 Superoxide production by unglycosylated Nox1 is largely dependent on p22(phox), which is abrogated by glutamine substitution for Pro-156 in p22(phox), a mutation leading to a defective interaction with the Nox1-activating protein Noxo1. 24365146 6 5 with interaction 1069:1079 arg1 Noxo1 1114:1118 the Nox1-activating protein Noxo1 1086:1118 the Nox1-activating protein Noxo1 1086:1118 Superoxide production by unglycosylated Nox1 is largely dependent on p22(phox), which is abrogated by glutamine substitution for Pro-156 in p22(phox), a mutation leading to a defective interaction with the Nox1-activating protein Noxo1. 24365146 2 6 theme extracellular 280:292 arg1 loops 294:298 the second and third extracellular loops 259:298 the second and third extracellular loops 259:298 Here we show that human Nox1 undergoes glycosylation at Asn-162 and Asn-236 in the second and third extracellular loops, respectively. 24365146 3 7 theme cell 498:501 arg1 surface 503:509 the cell surface 494:509 the cell surface 494:509 Simultaneous threonine substitution for these residues completely abrogates the glycosylation, but does not prevent Nox1 from forming a heterodimer with p22(phox), trafficking to the cell surface, or producing superoxide. 24365146 7 8 theme glycosylation-independent 1181:1205 arg1 manner 1207:1212 a glycosylation-independent manner 1179:1212 a glycosylation-independent manner 1179:1212 Thus p22(phox) directly contributes to Nox1 activation in a glycosylation-independent manner, besides its significant role in Nox1 glycan maturation. 24365146 2 9 theme third 274:278 arg1 loops 294:298 the second and third extracellular loops 259:298 the second and third extracellular loops 259:298 Here we show that human Nox1 undergoes glycosylation at Asn-162 and Asn-236 in the second and third extracellular loops, respectively. 24365146 7 10 theme glycan 1252:1257 arg1 maturation 1259:1268 Nox1 glycan maturation 1247:1268 Nox1 glycan maturation 1247:1268 Thus p22(phox) directly contributes to Nox1 activation in a glycosylation-independent manner, besides its significant role in Nox1 glycan maturation. 24365146 5 11 gly glycosylation 772:784 arg1 Nox1 824:827 Nox1 824:827 Nox1 824:827 These findings indicate that glycosylation and subsequent N-glycan maturation of Nox1 are both dispensable for its cell surface recruitment. 24365146 1 12 theme membrane-integrated 81:99 arg1 protein 101:107 a membrane-integrated protein 79:107 a membrane-integrated protein that belongs to the Nox family of superoxide-producing NADPH oxidases 79:177 Nox1 is a membrane-integrated protein that belongs to the Nox family of superoxide-producing NADPH oxidases. 24365146 1 12 theme membrane-integrated 81:99 arg1 Nox1 71:74 Nox1 71:74 Nox1 71:74 Nox1 is a membrane-integrated protein that belongs to the Nox family of superoxide-producing NADPH oxidases. 24365146 2 13 from Asn-162 236:242 arg1 glycosylation 219:231 glycosylation 219:231 glycosylation at Asn-162 and Asn-236 219:254 Here we show that human Nox1 undergoes glycosylation at Asn-162 and Asn-236 in the second and third extracellular loops, respectively. 24365146 5 14 theme Nox1 824:827 arg1 glycosylation 772:784 glycosylation 772:784 glycosylation 772:784 These findings indicate that glycosylation and subsequent N-glycan maturation of Nox1 are both dispensable for its cell surface recruitment. 24365146 5 14 theme Nox1 824:827 arg1 maturation 810:819 subsequent N-glycan maturation 790:819 subsequent N-glycan maturation of Nox1 790:827 These findings indicate that glycosylation and subsequent N-glycan maturation of Nox1 are both dispensable for its cell surface recruitment. 24365146 0 15 theme N-Linked 0:7 arg1 glycosylation 9:21 N-Linked glycosylation 0:21 N-Linked glycosylation of the superoxide-producing NADPH oxidase Nox1. 0:69 N-Linked glycosylation of the superoxide-producing NADPH oxidase Nox1. 24365146 4 16 theme complex 686:692 arg1 N-glycans 694:702 complex N-glycans 686:702 complex N-glycans 686:702 In the absence of p22(phox), Nox1 is transported to the plasma membrane mainly as a form with high mannose N-glycans, although their conversion into complex N-glycans is induced by expression of p22(phox). 24365146 7 17 theme Nox1 1247:1250 arg1 maturation 1259:1268 Nox1 glycan maturation 1247:1268 Nox1 glycan maturation 1247:1268 Thus p22(phox) directly contributes to Nox1 activation in a glycosylation-independent manner, besides its significant role in Nox1 glycan maturation. 24365146 6 18 theme defective 1059:1067 arg1 interaction 1069:1079 a defective interaction 1057:1079 a defective interaction with the Nox1-activating protein Noxo1 1057:1118 Superoxide production by unglycosylated Nox1 is largely dependent on p22(phox), which is abrogated by glutamine substitution for Pro-156 in p22(phox), a mutation leading to a defective interaction with the Nox1-activating protein Noxo1. 24365146 2 19 from Asn-236 248:254 arg1 glycosylation 219:231 glycosylation 219:231 glycosylation at Asn-162 and Asn-236 219:254 Here we show that human Nox1 undergoes glycosylation at Asn-162 and Asn-236 in the second and third extracellular loops, respectively. 24365146 4 20 theme plasma 593:598 arg1 membrane 600:607 the plasma membrane 589:607 the plasma membrane 589:607 In the absence of p22(phox), Nox1 is transported to the plasma membrane mainly as a form with high mannose N-glycans, although their conversion into complex N-glycans is induced by expression of p22(phox). 24365146 4 21 theme p22 555:557 arg1 absence 544:550 the absence 540:550 the absence of p22(phox) 540:563 In the absence of p22(phox), Nox1 is transported to the plasma membrane mainly as a form with high mannose N-glycans, although their conversion into complex N-glycans is induced by expression of p22(phox). 24365146 4 22 theme p22 732:734 arg1 expression 718:727 expression 718:727 expression of p22(phox) 718:740 In the absence of p22(phox), Nox1 is transported to the plasma membrane mainly as a form with high mannose N-glycans, although their conversion into complex N-glycans is induced by expression of p22(phox). 24365146 7 23 theme Nox1 1160:1163 arg1 activation 1165:1174 Nox1 activation 1160:1174 Nox1 activation 1160:1174 Thus p22(phox) directly contributes to Nox1 activation in a glycosylation-independent manner, besides its significant role in Nox1 glycan maturation. 24365146 6 24 theme glutamine 986:994 arg1 substitution 996:1007 glutamine substitution 986:1007 glutamine substitution for Pro-156 in p22(phox), a mutation leading to a defective interaction with the Nox1-activating protein Noxo1 986:1118 Superoxide production by unglycosylated Nox1 is largely dependent on p22(phox), which is abrogated by glutamine substitution for Pro-156 in p22(phox), a mutation leading to a defective interaction with the Nox1-activating protein Noxo1. 24365146 0 25 theme NADPH 51:55 arg1 Nox1 65:68 the superoxide-producing NADPH oxidase Nox1 26:68 the superoxide-producing NADPH oxidase Nox1 26:68 N-Linked glycosylation of the superoxide-producing NADPH oxidase Nox1. 24365146 4 26 with form 621:624 arg1 N-glycans 644:652 high mannose N-glycans 631:652 high mannose N-glycans 631:652 In the absence of p22(phox), Nox1 is transported to the plasma membrane mainly as a form with high mannose N-glycans, although their conversion into complex N-glycans is induced by expression of p22(phox). 24365146 5 27 theme subsequent 790:799 arg1 maturation 810:819 subsequent N-glycan maturation 790:819 subsequent N-glycan maturation of Nox1 790:827 These findings indicate that glycosylation and subsequent N-glycan maturation of Nox1 are both dispensable for its cell surface recruitment. 24365146 0 28 theme superoxide-producing 30:49 arg1 Nox1 65:68 the superoxide-producing NADPH oxidase Nox1 26:68 the superoxide-producing NADPH oxidase Nox1 26:68 N-Linked glycosylation of the superoxide-producing NADPH oxidase Nox1. 24365146 6 29 theme unglycosylated 909:922 arg1 Nox1 924:927 unglycosylated Nox1 909:927 unglycosylated Nox1 909:927 Superoxide production by unglycosylated Nox1 is largely dependent on p22(phox), which is abrogated by glutamine substitution for Pro-156 in p22(phox), a mutation leading to a defective interaction with the Nox1-activating protein Noxo1. 24365146 0 30 gly glycosylation 9:21 arg1 Nox1 65:68 the superoxide-producing NADPH oxidase Nox1 26:68 the superoxide-producing NADPH oxidase Nox1 26:68 N-Linked glycosylation of the superoxide-producing NADPH oxidase Nox1. 24365146 5 31 theme N-glycan 801:808 arg1 maturation 810:819 subsequent N-glycan maturation 790:819 subsequent N-glycan maturation of Nox1 790:827 These findings indicate that glycosylation and subsequent N-glycan maturation of Nox1 are both dispensable for its cell surface recruitment. 24365146 0 32 theme Nox1 65:68 arg1 glycosylation 9:21 N-Linked glycosylation 0:21 N-Linked glycosylation of the superoxide-producing NADPH oxidase Nox1. 0:69 N-Linked glycosylation of the superoxide-producing NADPH oxidase Nox1. 24365146 5 33 theme cell 858:861 arg1 recruitment 871:881 its cell surface recruitment 854:881 its cell surface recruitment 854:881 These findings indicate that glycosylation and subsequent N-glycan maturation of Nox1 are both dispensable for its cell surface recruitment. 24365146 0 34 theme oxidase 57:63 arg1 Nox1 65:68 the superoxide-producing NADPH oxidase Nox1 26:68 the superoxide-producing NADPH oxidase Nox1 26:68 N-Linked glycosylation of the superoxide-producing NADPH oxidase Nox1. 24365146 6 35 theme protein 1106:1112 arg1 Noxo1 1114:1118 the Nox1-activating protein Noxo1 1086:1118 the Nox1-activating protein Noxo1 1086:1118 Superoxide production by unglycosylated Nox1 is largely dependent on p22(phox), which is abrogated by glutamine substitution for Pro-156 in p22(phox), a mutation leading to a defective interaction with the Nox1-activating protein Noxo1. 24365146 3 36 theme Simultaneous 315:326 arg1 substitution 338:349 Simultaneous threonine substitution 315:349 Simultaneous threonine substitution for these residues 315:368 Simultaneous threonine substitution for these residues completely abrogates the glycosylation, but does not prevent Nox1 from forming a heterodimer with p22(phox), trafficking to the cell surface, or producing superoxide. 24365146 5 37 theme surface 863:869 arg1 recruitment 871:881 its cell surface recruitment 854:881 its cell surface recruitment 854:881 These findings indicate that glycosylation and subsequent N-glycan maturation of Nox1 are both dispensable for its cell surface recruitment. 24365146 6 38 theme Superoxide 884:893 arg1 production 895:904 Superoxide production 884:904 Superoxide production by unglycosylated Nox1 884:927 Superoxide production by unglycosylated Nox1 is largely dependent on p22(phox), which is abrogated by glutamine substitution for Pro-156 in p22(phox), a mutation leading to a defective interaction with the Nox1-activating protein Noxo1. 24365146 3 39 with heterodimer 451:461 arg1 phox 472:475 phox 472:475 phox 472:475 Simultaneous threonine substitution for these residues completely abrogates the glycosylation, but does not prevent Nox1 from forming a heterodimer with p22(phox), trafficking to the cell surface, or producing superoxide. 24365146 3 39 with heterodimer 451:461 arg1 trafficking 479:489 trafficking 479:489 trafficking to the cell surface 479:509 Simultaneous threonine substitution for these residues completely abrogates the glycosylation, but does not prevent Nox1 from forming a heterodimer with p22(phox), trafficking to the cell surface, or producing superoxide. 24365146 3 39 with heterodimer 451:461 arg1 p22 468:470 p22 468:470 p22(phox) 468:476 Simultaneous threonine substitution for these residues completely abrogates the glycosylation, but does not prevent Nox1 from forming a heterodimer with p22(phox), trafficking to the cell surface, or producing superoxide. 24365146 2 40 theme second 263:268 arg1 loops 294:298 the second and third extracellular loops 259:298 the second and third extracellular loops 259:298 Here we show that human Nox1 undergoes glycosylation at Asn-162 and Asn-236 in the second and third extracellular loops, respectively. 24365146 7 41 from role 1239:1242 arg1 maturation 1259:1268 Nox1 glycan maturation 1247:1268 Nox1 glycan maturation 1247:1268 Thus p22(phox) directly contributes to Nox1 activation in a glycosylation-independent manner, besides its significant role in Nox1 glycan maturation. 24365146 1 42 theme Nox 129:131 arg1 family 133:138 the Nox family 125:138 the Nox family of superoxide-producing NADPH oxidases 125:177 Nox1 is a membrane-integrated protein that belongs to the Nox family of superoxide-producing NADPH oxidases. 24365146 2 43 theme human 198:202 arg1 Nox1 204:207 human Nox1 198:207 human Nox1 198:207 Here we show that human Nox1 undergoes glycosylation at Asn-162 and Asn-236 in the second and third extracellular loops, respectively. 24365146 4 44 theme high 631:634 arg1 N-glycans 644:652 high mannose N-glycans 631:652 high mannose N-glycans 631:652 In the absence of p22(phox), Nox1 is transported to the plasma membrane mainly as a form with high mannose N-glycans, although their conversion into complex N-glycans is induced by expression of p22(phox). 24365146 7 45 theme significant 1227:1237 arg1 role 1239:1242 its significant role 1223:1242 its significant role in Nox1 glycan maturation 1223:1268 Thus p22(phox) directly contributes to Nox1 activation in a glycosylation-independent manner, besides its significant role in Nox1 glycan maturation. 24365146 4 46 theme mannose 636:642 arg1 N-glycans 644:652 high mannose N-glycans 631:652 high mannose N-glycans 631:652 In the absence of p22(phox), Nox1 is transported to the plasma membrane mainly as a form with high mannose N-glycans, although their conversion into complex N-glycans is induced by expression of p22(phox). 24365146 6 47 theme Nox1-activating 1090:1104 arg1 Noxo1 1114:1118 the Nox1-activating protein Noxo1 1086:1118 the Nox1-activating protein Noxo1 1086:1118 Superoxide production by unglycosylated Nox1 is largely dependent on p22(phox), which is abrogated by glutamine substitution for Pro-156 in p22(phox), a mutation leading to a defective interaction with the Nox1-activating protein Noxo1. 24365146 2 48 gly glycosylation 219:231 arg2 Asn-236 248:254 Asn-236 248:254 Asn-236 248:254 Here we show that human Nox1 undergoes glycosylation at Asn-162 and Asn-236 in the second and third extracellular loops, respectively. 24365146 2 48 gly glycosylation 219:231 arg1 Asn-162 236:242 Asn-162 236:242 Asn-162 236:242 Here we show that human Nox1 undergoes glycosylation at Asn-162 and Asn-236 in the second and third extracellular loops, respectively. 24365146 2 48 gly glycosylation 219:231 arg1 loops 294:298 the second and third extracellular loops 259:298 the second and third extracellular loops 259:298 Here we show that human Nox1 undergoes glycosylation at Asn-162 and Asn-236 in the second and third extracellular loops, respectively. 24365146 2 48 gly glycosylation 219:231 arg1 Nox1 204:207 human Nox1 198:207 human Nox1 198:207 Here we show that human Nox1 undergoes glycosylation at Asn-162 and Asn-236 in the second and third extracellular loops, respectively. 24365146 2 48 gly glycosylation 219:231 arg1 Asn-236 248:254 Asn-236 248:254 Asn-236 248:254 Here we show that human Nox1 undergoes glycosylation at Asn-162 and Asn-236 in the second and third extracellular loops, respectively. 24365146 2 48 gly glycosylation 219:231 arg2 Asn-162 236:242 Asn-162 236:242 Asn-162 236:242 Here we show that human Nox1 undergoes glycosylation at Asn-162 and Asn-236 in the second and third extracellular loops, respectively. 24365146 1 49 theme superoxide-producing 143:162 arg1 oxidases 170:177 superoxide-producing NADPH oxidases 143:177 superoxide-producing NADPH oxidases 143:177 Nox1 is a membrane-integrated protein that belongs to the Nox family of superoxide-producing NADPH oxidases. 25682038 6 0 theme pathway 1140:1146 arg1 activity 1148:1155 increased hexosamine pathway activity 1119:1155 increased hexosamine pathway activity 1119:1155 Urea-induced ROS caused the activation of endothelial pro-inflammatory pathways through the inhibition of GAPDH, including increased protein kinase C isoforms activity, increased hexosamine pathway activity, and accumulation of intracellular AGEs (advanced glycation end products). 25682038 2 1 theme ROS 363:365 arg1 production 367:376 ROS production 363:376 ROS production 363:376 Here we investigate the hypothesis that concentrations of urea associated with CRF and increased ROS production in adipocytes might also increase ROS production directly in arterial endothelial cells, causing the same pathophysiologic changes seen with hyperglycemia. 25682038 9 2 theme oxidative 1485:1493 arg1 stress 1495:1500 aortic oxidative stress 1478:1500 aortic oxidative stress 1478:1500 In uremic mice, treatment with MnTBAP prevented aortic oxidative stress, PGI2 synthase activity reduction and increased expression of the pro-inflammatory proteins TNFα, IL-6, VCAM1, Endoglin, and MCP-1. 25682038 3 3 theme 20mM 567:570 arg1 urea 572:575 20mM urea 567:575 20mM urea 567:575 METHODS Primary cultures of human aortic endothelial cells (HAEC) were exposed to 20mM urea for 48 h. C57BL/6J wild-type mice underwent 5/6 nephrectomy or a sham operation. 25682038 1 4 dep OBJECTIVE 73:81 arg1 understood 205:214 understood 205:214 are poorly understood 194:214 OBJECTIVE The pathogenic events responsible for accelerated atherosclerosis in patients with chronic renal failure (CRF) are poorly understood. 25682038 10 5 theme pathways 1799:1806 arg1 activation 1770:1779 activation 1770:1779 activation of proatherogenic pathways 1770:1806 CONCLUSIONS Taken together, these data show that urea itself, at levels common in patients with CRF, causes endothelial dysfunction and activation of proatherogenic pathways. 25682038 10 5 theme pathways 1799:1806 arg1 dysfunction 1754:1764 endothelial dysfunction 1742:1764 endothelial dysfunction 1742:1764 CONCLUSIONS Taken together, these data show that urea itself, at levels common in patients with CRF, causes endothelial dysfunction and activation of proatherogenic pathways. 25682038 9 6 theme synthase 1508:1515 arg1 reduction 1526:1534 PGI2 synthase activity reduction 1503:1534 PGI2 synthase activity reduction 1503:1534 In uremic mice, treatment with MnTBAP prevented aortic oxidative stress, PGI2 synthase activity reduction and increased expression of the pro-inflammatory proteins TNFα, IL-6, VCAM1, Endoglin, and MCP-1. 25682038 6 7 theme glycation 1207:1215 arg1 products 1221:1228 advanced glycation end products 1198:1228 advanced glycation end products 1198:1228 Urea-induced ROS caused the activation of endothelial pro-inflammatory pathways through the inhibition of GAPDH, including increased protein kinase C isoforms activity, increased hexosamine pathway activity, and accumulation of intracellular AGEs (advanced glycation end products). 25682038 6 7 theme glycation 1207:1215 arg1 AGEs 1192:1195 intracellular AGEs 1178:1195 intracellular AGEs (advanced glycation end products) 1178:1229 Urea-induced ROS caused the activation of endothelial pro-inflammatory pathways through the inhibition of GAPDH, including increased protein kinase C isoforms activity, increased hexosamine pathway activity, and accumulation of intracellular AGEs (advanced glycation end products). 25682038 4 8 theme mice 698:701 arg1 controls 713:720 their controls 707:720 their controls 707:720 Randomized groups of 5/6 nephrectomized mice and their controls were also injected i.p. with a SOD/catalase mimetic (MnTBAP) for 15 days starting immediately after the final surgical procedure. 25682038 4 8 theme mice 698:701 arg1 groups 669:674 Randomized groups 658:674 Randomized groups of 5/6 nephrectomized mice and their controls 658:720 Randomized groups of 5/6 nephrectomized mice and their controls were also injected i.p. with a SOD/catalase mimetic (MnTBAP) for 15 days starting immediately after the final surgical procedure. 25682038 4 8 theme mice 698:701 arg1 mice 698:701 5/6 nephrectomized mice 679:701 5/6 nephrectomized mice 679:701 Randomized groups of 5/6 nephrectomized mice and their controls were also injected i.p. with a SOD/catalase mimetic (MnTBAP) for 15 days starting immediately after the final surgical procedure. 25682038 3 9 theme C57BL/6J 587:594 arg1 mice 606:609 48 h. C57BL/6J wild-type mice 581:609 48 h. C57BL/6J wild-type mice 581:609 METHODS Primary cultures of human aortic endothelial cells (HAEC) were exposed to 20mM urea for 48 h. C57BL/6J wild-type mice underwent 5/6 nephrectomy or a sham operation. 25682038 6 10 theme endothelial 992:1002 arg1 pathways 1021:1028 endothelial pro-inflammatory pathways 992:1028 endothelial pro-inflammatory pathways 992:1028 Urea-induced ROS caused the activation of endothelial pro-inflammatory pathways through the inhibition of GAPDH, including increased protein kinase C isoforms activity, increased hexosamine pathway activity, and accumulation of intracellular AGEs (advanced glycation end products). 25682038 2 11 theme increased 304:312 arg1 production 318:327 increased ROS production 304:327 increased ROS production in adipocytes 304:341 Here we investigate the hypothesis that concentrations of urea associated with CRF and increased ROS production in adipocytes might also increase ROS production directly in arterial endothelial cells, causing the same pathophysiologic changes seen with hyperglycemia. 25682038 5 12 theme RESULTS 852:858 arg1 Urea 860:863 RESULTS Urea 852:863 RESULTS Urea at concentrations seen in CRF 852:893 RESULTS Urea at concentrations seen in CRF induced mitochondrial ROS production in cultured HAEC. 25682038 4 13 dep mimetic 766:772 arg1 MnTBAP 775:780 MnTBAP 775:780 MnTBAP 775:780 Randomized groups of 5/6 nephrectomized mice and their controls were also injected i.p. with a SOD/catalase mimetic (MnTBAP) for 15 days starting immediately after the final surgical procedure. 25682038 8 14 theme mitochondrial 1360:1372 arg1 production 1378:1387 mitochondrial ROS production 1360:1387 mitochondrial ROS production 1360:1387 Normalization of mitochondrial ROS production prevented each of these effects of urea. 25682038 5 15 theme cultured 935:942 arg1 HAEC 944:947 cultured HAEC 935:947 cultured HAEC 935:947 RESULTS Urea at concentrations seen in CRF induced mitochondrial ROS production in cultured HAEC. 25682038 6 16 theme Urea-induced 950:961 arg1 ROS 963:965 Urea-induced ROS 950:965 Urea-induced ROS 950:965 Urea-induced ROS caused the activation of endothelial pro-inflammatory pathways through the inhibition of GAPDH, including increased protein kinase C isoforms activity, increased hexosamine pathway activity, and accumulation of intracellular AGEs (advanced glycation end products). 25682038 8 17 theme production 1378:1387 arg1 Normalization 1343:1355 Normalization 1343:1355 Normalization of mitochondrial ROS production 1343:1387 Normalization of mitochondrial ROS production prevented each of these effects of urea. 25682038 3 18 theme sham 642:645 arg1 operation 647:655 a sham operation 640:655 a sham operation 640:655 METHODS Primary cultures of human aortic endothelial cells (HAEC) were exposed to 20mM urea for 48 h. C57BL/6J wild-type mice underwent 5/6 nephrectomy or a sham operation. 25682038 3 19 theme Primary 493:499 arg1 cultures 501:508 Primary cultures 493:508 Primary cultures of human aortic endothelial cells (HAEC) 493:549 METHODS Primary cultures of human aortic endothelial cells (HAEC) were exposed to 20mM urea for 48 h. C57BL/6J wild-type mice underwent 5/6 nephrectomy or a sham operation. 25682038 9 20 theme pro-inflammatory 1568:1583 arg1 IL-6 1600:1603 IL-6 1600:1603 IL-6 1600:1603 In uremic mice, treatment with MnTBAP prevented aortic oxidative stress, PGI2 synthase activity reduction and increased expression of the pro-inflammatory proteins TNFα, IL-6, VCAM1, Endoglin, and MCP-1. 25682038 9 20 theme pro-inflammatory 1568:1583 arg1 MCP-1 1627:1631 MCP-1 1627:1631 MCP-1 1627:1631 In uremic mice, treatment with MnTBAP prevented aortic oxidative stress, PGI2 synthase activity reduction and increased expression of the pro-inflammatory proteins TNFα, IL-6, VCAM1, Endoglin, and MCP-1. 25682038 9 20 theme pro-inflammatory 1568:1583 arg1 VCAM1 1606:1610 VCAM1 1606:1610 VCAM1 1606:1610 In uremic mice, treatment with MnTBAP prevented aortic oxidative stress, PGI2 synthase activity reduction and increased expression of the pro-inflammatory proteins TNFα, IL-6, VCAM1, Endoglin, and MCP-1. 25682038 9 20 theme pro-inflammatory 1568:1583 arg1 proteins 1585:1592 the pro-inflammatory proteins TNFα, IL-6, VCAM1, Endoglin, and MCP-1 1564:1631 the pro-inflammatory proteins TNFα, IL-6, VCAM1, Endoglin, and MCP-1 1564:1631 In uremic mice, treatment with MnTBAP prevented aortic oxidative stress, PGI2 synthase activity reduction and increased expression of the pro-inflammatory proteins TNFα, IL-6, VCAM1, Endoglin, and MCP-1. 25682038 9 20 theme pro-inflammatory 1568:1583 arg1 TNFα 1594:1597 TNFα 1594:1597 TNFα 1594:1597 In uremic mice, treatment with MnTBAP prevented aortic oxidative stress, PGI2 synthase activity reduction and increased expression of the pro-inflammatory proteins TNFα, IL-6, VCAM1, Endoglin, and MCP-1. 25682038 9 20 theme pro-inflammatory 1568:1583 arg1 Endoglin 1613:1620 Endoglin 1613:1620 Endoglin 1613:1620 In uremic mice, treatment with MnTBAP prevented aortic oxidative stress, PGI2 synthase activity reduction and increased expression of the pro-inflammatory proteins TNFα, IL-6, VCAM1, Endoglin, and MCP-1. 25682038 7 21 theme PGI2 1302:1305 arg1 synthase 1307:1314 the anti-atherosclerosis enzyme PGI2 synthase 1270:1314 the anti-atherosclerosis enzyme PGI2 synthase 1270:1314 Urea-induced ROS directly inactivated the anti-atherosclerosis enzyme PGI2 synthase and also caused ER stress. 25682038 5 22 from concentrations 868:881 arg1 Urea 860:863 RESULTS Urea 852:863 RESULTS Urea at concentrations seen in CRF 852:893 RESULTS Urea at concentrations seen in CRF induced mitochondrial ROS production in cultured HAEC. 25682038 5 23 theme mitochondrial 903:915 arg1 production 921:930 mitochondrial ROS production 903:930 mitochondrial ROS production 903:930 RESULTS Urea at concentrations seen in CRF induced mitochondrial ROS production in cultured HAEC. 25682038 7 24 theme anti-atherosclerosis 1274:1293 arg1 synthase 1307:1314 the anti-atherosclerosis enzyme PGI2 synthase 1270:1314 the anti-atherosclerosis enzyme PGI2 synthase 1270:1314 Urea-induced ROS directly inactivated the anti-atherosclerosis enzyme PGI2 synthase and also caused ER stress. 25682038 9 25 dep proteins 1585:1592 arg1 IL-6 1600:1603 IL-6 1600:1603 IL-6 1600:1603 In uremic mice, treatment with MnTBAP prevented aortic oxidative stress, PGI2 synthase activity reduction and increased expression of the pro-inflammatory proteins TNFα, IL-6, VCAM1, Endoglin, and MCP-1. 25682038 9 25 dep proteins 1585:1592 arg1 MCP-1 1627:1631 MCP-1 1627:1631 MCP-1 1627:1631 In uremic mice, treatment with MnTBAP prevented aortic oxidative stress, PGI2 synthase activity reduction and increased expression of the pro-inflammatory proteins TNFα, IL-6, VCAM1, Endoglin, and MCP-1. 25682038 9 25 dep proteins 1585:1592 arg1 VCAM1 1606:1610 VCAM1 1606:1610 VCAM1 1606:1610 In uremic mice, treatment with MnTBAP prevented aortic oxidative stress, PGI2 synthase activity reduction and increased expression of the pro-inflammatory proteins TNFα, IL-6, VCAM1, Endoglin, and MCP-1. 25682038 9 25 dep proteins 1585:1592 arg1 proteins 1585:1592 the pro-inflammatory proteins TNFα, IL-6, VCAM1, Endoglin, and MCP-1 1564:1631 the pro-inflammatory proteins TNFα, IL-6, VCAM1, Endoglin, and MCP-1 1564:1631 In uremic mice, treatment with MnTBAP prevented aortic oxidative stress, PGI2 synthase activity reduction and increased expression of the pro-inflammatory proteins TNFα, IL-6, VCAM1, Endoglin, and MCP-1. 25682038 9 25 dep proteins 1585:1592 arg1 TNFα 1594:1597 TNFα 1594:1597 TNFα 1594:1597 In uremic mice, treatment with MnTBAP prevented aortic oxidative stress, PGI2 synthase activity reduction and increased expression of the pro-inflammatory proteins TNFα, IL-6, VCAM1, Endoglin, and MCP-1. 25682038 9 25 dep proteins 1585:1592 arg1 Endoglin 1613:1620 Endoglin 1613:1620 Endoglin 1613:1620 In uremic mice, treatment with MnTBAP prevented aortic oxidative stress, PGI2 synthase activity reduction and increased expression of the pro-inflammatory proteins TNFα, IL-6, VCAM1, Endoglin, and MCP-1. 25682038 6 26 theme pathways 1021:1028 arg1 activation 978:987 the activation 974:987 the activation of endothelial pro-inflammatory pathways 974:1028 Urea-induced ROS caused the activation of endothelial pro-inflammatory pathways through the inhibition of GAPDH, including increased protein kinase C isoforms activity, increased hexosamine pathway activity, and accumulation of intracellular AGEs (advanced glycation end products). 25682038 10 27 theme common 1706:1711 arg1 levels 1699:1704 levels 1699:1704 levels common in patients with CRF 1699:1732 CONCLUSIONS Taken together, these data show that urea itself, at levels common in patients with CRF, causes endothelial dysfunction and activation of proatherogenic pathways. 25682038 1 28 with patients 152:159 arg1 CRF 189:191 CRF 189:191 CRF 189:191 OBJECTIVE The pathogenic events responsible for accelerated atherosclerosis in patients with chronic renal failure (CRF) are poorly understood. 25682038 1 28 with patients 152:159 arg1 failure 180:186 chronic renal failure 166:186 chronic renal failure (CRF) 166:192 OBJECTIVE The pathogenic events responsible for accelerated atherosclerosis in patients with chronic renal failure (CRF) are poorly understood. 25682038 0 29 from dysfunction 35:45 arg1 failure 64:70 chronic renal failure 50:70 chronic renal failure 50:70 Urea-induced ROS cause endothelial dysfunction in chronic renal failure. 25682038 2 30 theme endothelial 399:409 arg1 cells 411:415 arterial endothelial cells 390:415 arterial endothelial cells 390:415 Here we investigate the hypothesis that concentrations of urea associated with CRF and increased ROS production in adipocytes might also increase ROS production directly in arterial endothelial cells, causing the same pathophysiologic changes seen with hyperglycemia. 25682038 0 31 theme Urea-induced 0:11 arg1 ROS 13:15 Urea-induced ROS 0:15 Urea-induced ROS 0:15 Urea-induced ROS cause endothelial dysfunction in chronic renal failure. 25682038 2 32 from concentrations 257:270 arg1 adipocytes 332:341 adipocytes 332:341 adipocytes 332:341 Here we investigate the hypothesis that concentrations of urea associated with CRF and increased ROS production in adipocytes might also increase ROS production directly in arterial endothelial cells, causing the same pathophysiologic changes seen with hyperglycemia. 25682038 6 33 theme isoforms 1100:1107 arg1 activity 1109:1116 increased protein kinase C isoforms activity 1073:1116 increased protein kinase C isoforms activity 1073:1116 Urea-induced ROS caused the activation of endothelial pro-inflammatory pathways through the inhibition of GAPDH, including increased protein kinase C isoforms activity, increased hexosamine pathway activity, and accumulation of intracellular AGEs (advanced glycation end products). 25682038 2 34 theme pathophysiologic 435:450 arg1 changes 452:458 the same pathophysiologic changes 426:458 the same pathophysiologic changes seen with hyperglycemia 426:482 Here we investigate the hypothesis that concentrations of urea associated with CRF and increased ROS production in adipocytes might also increase ROS production directly in arterial endothelial cells, causing the same pathophysiologic changes seen with hyperglycemia. 25682038 6 35 theme kinase 1091:1096 arg1 C 1098:1098 protein kinase C 1083:1098 increased protein kinase C isoforms activity 1073:1116 Urea-induced ROS caused the activation of endothelial pro-inflammatory pathways through the inhibition of GAPDH, including increased protein kinase C isoforms activity, increased hexosamine pathway activity, and accumulation of intracellular AGEs (advanced glycation end products). 25682038 4 36 theme final 826:830 arg1 procedure 841:849 the final surgical procedure 822:849 the final surgical procedure 822:849 Randomized groups of 5/6 nephrectomized mice and their controls were also injected i.p. with a SOD/catalase mimetic (MnTBAP) for 15 days starting immediately after the final surgical procedure. 25682038 6 37 theme increased 1073:1081 arg1 activity 1109:1116 increased protein kinase C isoforms activity 1073:1116 increased protein kinase C isoforms activity 1073:1116 Urea-induced ROS caused the activation of endothelial pro-inflammatory pathways through the inhibition of GAPDH, including increased protein kinase C isoforms activity, increased hexosamine pathway activity, and accumulation of intracellular AGEs (advanced glycation end products). 25682038 3 38 theme aortic 519:524 arg1 HAEC 545:548 HAEC 545:548 HAEC 545:548 METHODS Primary cultures of human aortic endothelial cells (HAEC) were exposed to 20mM urea for 48 h. C57BL/6J wild-type mice underwent 5/6 nephrectomy or a sham operation. 25682038 3 38 theme aortic 519:524 arg1 cells 538:542 human aortic endothelial cells 513:542 human aortic endothelial cells (HAEC) 513:549 METHODS Primary cultures of human aortic endothelial cells (HAEC) were exposed to 20mM urea for 48 h. C57BL/6J wild-type mice underwent 5/6 nephrectomy or a sham operation. 25682038 0 39 theme chronic 50:56 arg1 failure 64:70 chronic renal failure 50:70 chronic renal failure 50:70 Urea-induced ROS cause endothelial dysfunction in chronic renal failure. 25682038 10 40 from common 1706:1711 arg1 patients 1716:1723 patients 1716:1723 patients with CRF 1716:1732 CONCLUSIONS Taken together, these data show that urea itself, at levels common in patients with CRF, causes endothelial dysfunction and activation of proatherogenic pathways. 25682038 3 41 dep METHODS 485:491 arg1 exposed 556:562 exposed 556:562 were exposed to 20mM urea for 48 h. C57BL/6J wild-type mice 551:609 METHODS Primary cultures of human aortic endothelial cells (HAEC) were exposed to 20mM urea for 48 h. C57BL/6J wild-type mice underwent 5/6 nephrectomy or a sham operation. 25682038 10 42 from patients 1716:1723 arg1 common 1706:1711 common 1706:1711 common 1706:1711 CONCLUSIONS Taken together, these data show that urea itself, at levels common in patients with CRF, causes endothelial dysfunction and activation of proatherogenic pathways. 25682038 1 43 theme chronic 166:172 arg1 CRF 189:191 CRF 189:191 CRF 189:191 OBJECTIVE The pathogenic events responsible for accelerated atherosclerosis in patients with chronic renal failure (CRF) are poorly understood. 25682038 1 43 theme chronic 166:172 arg1 failure 180:186 chronic renal failure 166:186 chronic renal failure (CRF) 166:192 OBJECTIVE The pathogenic events responsible for accelerated atherosclerosis in patients with chronic renal failure (CRF) are poorly understood. 25682038 10 44 theme proatherogenic 1784:1797 arg1 pathways 1799:1806 proatherogenic pathways 1784:1806 proatherogenic pathways 1784:1806 CONCLUSIONS Taken together, these data show that urea itself, at levels common in patients with CRF, causes endothelial dysfunction and activation of proatherogenic pathways. 25682038 3 45 theme cells 538:542 arg1 cultures 501:508 Primary cultures 493:508 Primary cultures of human aortic endothelial cells (HAEC) 493:549 METHODS Primary cultures of human aortic endothelial cells (HAEC) were exposed to 20mM urea for 48 h. C57BL/6J wild-type mice underwent 5/6 nephrectomy or a sham operation. 25682038 9 46 theme aortic 1478:1483 arg1 stress 1495:1500 aortic oxidative stress 1478:1500 aortic oxidative stress 1478:1500 In uremic mice, treatment with MnTBAP prevented aortic oxidative stress, PGI2 synthase activity reduction and increased expression of the pro-inflammatory proteins TNFα, IL-6, VCAM1, Endoglin, and MCP-1. 25682038 6 47 theme hexosamine 1129:1138 arg1 activity 1148:1155 increased hexosamine pathway activity 1119:1155 increased hexosamine pathway activity 1119:1155 Urea-induced ROS caused the activation of endothelial pro-inflammatory pathways through the inhibition of GAPDH, including increased protein kinase C isoforms activity, increased hexosamine pathway activity, and accumulation of intracellular AGEs (advanced glycation end products). 25682038 10 48 with patients 1716:1723 arg1 CRF 1730:1732 CRF 1730:1732 CRF 1730:1732 CONCLUSIONS Taken together, these data show that urea itself, at levels common in patients with CRF, causes endothelial dysfunction and activation of proatherogenic pathways. 25682038 5 49 theme ROS 917:919 arg1 production 921:930 mitochondrial ROS production 903:930 mitochondrial ROS production 903:930 RESULTS Urea at concentrations seen in CRF induced mitochondrial ROS production in cultured HAEC. 25682038 9 50 theme PGI2 1503:1506 arg1 synthase 1508:1515 PGI2 synthase 1503:1515 PGI2 synthase activity reduction 1503:1534 In uremic mice, treatment with MnTBAP prevented aortic oxidative stress, PGI2 synthase activity reduction and increased expression of the pro-inflammatory proteins TNFα, IL-6, VCAM1, Endoglin, and MCP-1. 25682038 6 51 theme end 1217:1219 arg1 products 1221:1228 advanced glycation end products 1198:1228 advanced glycation end products 1198:1228 Urea-induced ROS caused the activation of endothelial pro-inflammatory pathways through the inhibition of GAPDH, including increased protein kinase C isoforms activity, increased hexosamine pathway activity, and accumulation of intracellular AGEs (advanced glycation end products). 25682038 6 51 theme end 1217:1219 arg1 AGEs 1192:1195 intracellular AGEs 1178:1195 intracellular AGEs (advanced glycation end products) 1178:1229 Urea-induced ROS caused the activation of endothelial pro-inflammatory pathways through the inhibition of GAPDH, including increased protein kinase C isoforms activity, increased hexosamine pathway activity, and accumulation of intracellular AGEs (advanced glycation end products). 25682038 3 52 theme 48 h. 581:585 arg1 mice 606:609 48 h. C57BL/6J wild-type mice 581:609 48 h. C57BL/6J wild-type mice 581:609 METHODS Primary cultures of human aortic endothelial cells (HAEC) were exposed to 20mM urea for 48 h. C57BL/6J wild-type mice underwent 5/6 nephrectomy or a sham operation. 25682038 9 53 theme activity 1517:1524 arg1 reduction 1526:1534 PGI2 synthase activity reduction 1503:1534 PGI2 synthase activity reduction 1503:1534 In uremic mice, treatment with MnTBAP prevented aortic oxidative stress, PGI2 synthase activity reduction and increased expression of the pro-inflammatory proteins TNFα, IL-6, VCAM1, Endoglin, and MCP-1. 25682038 6 54 theme pro-inflammatory 1004:1019 arg1 pathways 1021:1028 endothelial pro-inflammatory pathways 992:1028 endothelial pro-inflammatory pathways 992:1028 Urea-induced ROS caused the activation of endothelial pro-inflammatory pathways through the inhibition of GAPDH, including increased protein kinase C isoforms activity, increased hexosamine pathway activity, and accumulation of intracellular AGEs (advanced glycation end products). 25682038 6 55 theme advanced 1198:1205 arg1 products 1221:1228 advanced glycation end products 1198:1228 advanced glycation end products 1198:1228 Urea-induced ROS caused the activation of endothelial pro-inflammatory pathways through the inhibition of GAPDH, including increased protein kinase C isoforms activity, increased hexosamine pathway activity, and accumulation of intracellular AGEs (advanced glycation end products). 25682038 6 55 theme advanced 1198:1205 arg1 AGEs 1192:1195 intracellular AGEs 1178:1195 intracellular AGEs (advanced glycation end products) 1178:1229 Urea-induced ROS caused the activation of endothelial pro-inflammatory pathways through the inhibition of GAPDH, including increased protein kinase C isoforms activity, increased hexosamine pathway activity, and accumulation of intracellular AGEs (advanced glycation end products). 25682038 4 56 theme nephrectomized 683:696 arg1 mice 698:701 5/6 nephrectomized mice 679:701 5/6 nephrectomized mice 679:701 Randomized groups of 5/6 nephrectomized mice and their controls were also injected i.p. with a SOD/catalase mimetic (MnTBAP) for 15 days starting immediately after the final surgical procedure. 25682038 2 57 theme ROS 314:316 arg1 production 318:327 increased ROS production 304:327 increased ROS production in adipocytes 304:341 Here we investigate the hypothesis that concentrations of urea associated with CRF and increased ROS production in adipocytes might also increase ROS production directly in arterial endothelial cells, causing the same pathophysiologic changes seen with hyperglycemia. 25682038 6 58 theme AGEs 1192:1195 arg1 activity 1148:1155 increased hexosamine pathway activity 1119:1155 increased hexosamine pathway activity 1119:1155 Urea-induced ROS caused the activation of endothelial pro-inflammatory pathways through the inhibition of GAPDH, including increased protein kinase C isoforms activity, increased hexosamine pathway activity, and accumulation of intracellular AGEs (advanced glycation end products). 25682038 6 58 theme AGEs 1192:1195 arg1 activity 1109:1116 increased protein kinase C isoforms activity 1073:1116 increased protein kinase C isoforms activity 1073:1116 Urea-induced ROS caused the activation of endothelial pro-inflammatory pathways through the inhibition of GAPDH, including increased protein kinase C isoforms activity, increased hexosamine pathway activity, and accumulation of intracellular AGEs (advanced glycation end products). 25682038 6 58 theme AGEs 1192:1195 arg1 accumulation 1162:1173 accumulation 1162:1173 accumulation of intracellular AGEs (advanced glycation end products) 1162:1229 Urea-induced ROS caused the activation of endothelial pro-inflammatory pathways through the inhibition of GAPDH, including increased protein kinase C isoforms activity, increased hexosamine pathway activity, and accumulation of intracellular AGEs (advanced glycation end products). 25682038 10 59 theme endothelial 1742:1752 arg1 dysfunction 1754:1764 endothelial dysfunction 1742:1764 endothelial dysfunction 1742:1764 CONCLUSIONS Taken together, these data show that urea itself, at levels common in patients with CRF, causes endothelial dysfunction and activation of proatherogenic pathways. 25682038 4 60 theme Randomized 658:667 arg1 controls 713:720 their controls 707:720 their controls 707:720 Randomized groups of 5/6 nephrectomized mice and their controls were also injected i.p. with a SOD/catalase mimetic (MnTBAP) for 15 days starting immediately after the final surgical procedure. 25682038 4 60 theme Randomized 658:667 arg1 groups 669:674 Randomized groups 658:674 Randomized groups of 5/6 nephrectomized mice and their controls 658:720 Randomized groups of 5/6 nephrectomized mice and their controls were also injected i.p. with a SOD/catalase mimetic (MnTBAP) for 15 days starting immediately after the final surgical procedure. 25682038 4 60 theme Randomized 658:667 arg1 mice 698:701 5/6 nephrectomized mice 679:701 5/6 nephrectomized mice 679:701 Randomized groups of 5/6 nephrectomized mice and their controls were also injected i.p. with a SOD/catalase mimetic (MnTBAP) for 15 days starting immediately after the final surgical procedure. 25682038 3 61 theme wild-type 596:604 arg1 mice 606:609 48 h. C57BL/6J wild-type mice 581:609 48 h. C57BL/6J wild-type mice 581:609 METHODS Primary cultures of human aortic endothelial cells (HAEC) were exposed to 20mM urea for 48 h. C57BL/6J wild-type mice underwent 5/6 nephrectomy or a sham operation. 25682038 1 62 theme accelerated 121:131 arg1 atherosclerosis 133:147 accelerated atherosclerosis 121:147 accelerated atherosclerosis in patients with chronic renal failure (CRF) 121:192 OBJECTIVE The pathogenic events responsible for accelerated atherosclerosis in patients with chronic renal failure (CRF) are poorly understood. 25682038 2 63 theme urea 275:278 arg1 concentrations 257:270 concentrations 257:270 concentrations of urea associated with CRF 257:298 Here we investigate the hypothesis that concentrations of urea associated with CRF and increased ROS production in adipocytes might also increase ROS production directly in arterial endothelial cells, causing the same pathophysiologic changes seen with hyperglycemia. 25682038 2 63 theme urea 275:278 arg1 production 318:327 increased ROS production 304:327 increased ROS production in adipocytes 304:341 Here we investigate the hypothesis that concentrations of urea associated with CRF and increased ROS production in adipocytes might also increase ROS production directly in arterial endothelial cells, causing the same pathophysiologic changes seen with hyperglycemia. 25682038 9 64 theme proteins 1585:1592 arg1 expression 1550:1559 increased expression 1540:1559 increased expression of the pro-inflammatory proteins TNFα, IL-6, VCAM1, Endoglin, and MCP-1 1540:1631 In uremic mice, treatment with MnTBAP prevented aortic oxidative stress, PGI2 synthase activity reduction and increased expression of the pro-inflammatory proteins TNFα, IL-6, VCAM1, Endoglin, and MCP-1. 25682038 9 64 theme proteins 1585:1592 arg1 reduction 1526:1534 PGI2 synthase activity reduction 1503:1534 PGI2 synthase activity reduction 1503:1534 In uremic mice, treatment with MnTBAP prevented aortic oxidative stress, PGI2 synthase activity reduction and increased expression of the pro-inflammatory proteins TNFα, IL-6, VCAM1, Endoglin, and MCP-1. 25682038 9 64 theme proteins 1585:1592 arg1 stress 1495:1500 aortic oxidative stress 1478:1500 aortic oxidative stress 1478:1500 In uremic mice, treatment with MnTBAP prevented aortic oxidative stress, PGI2 synthase activity reduction and increased expression of the pro-inflammatory proteins TNFα, IL-6, VCAM1, Endoglin, and MCP-1. 25682038 8 65 theme ROS 1374:1376 arg1 production 1378:1387 mitochondrial ROS production 1360:1387 mitochondrial ROS production 1360:1387 Normalization of mitochondrial ROS production prevented each of these effects of urea. 25682038 7 66 theme enzyme 1295:1300 arg1 synthase 1307:1314 the anti-atherosclerosis enzyme PGI2 synthase 1270:1314 the anti-atherosclerosis enzyme PGI2 synthase 1270:1314 Urea-induced ROS directly inactivated the anti-atherosclerosis enzyme PGI2 synthase and also caused ER stress. 25682038 6 67 theme GAPDH 1056:1060 arg1 inhibition 1042:1051 the inhibition 1038:1051 the inhibition of GAPDH, including increased protein kinase C isoforms activity, increased hexosamine pathway activity, and accumulation of intracellular AGEs (advanced glycation end products) 1038:1229 Urea-induced ROS caused the activation of endothelial pro-inflammatory pathways through the inhibition of GAPDH, including increased protein kinase C isoforms activity, increased hexosamine pathway activity, and accumulation of intracellular AGEs (advanced glycation end products). 25682038 1 68 theme renal 174:178 arg1 CRF 189:191 CRF 189:191 CRF 189:191 OBJECTIVE The pathogenic events responsible for accelerated atherosclerosis in patients with chronic renal failure (CRF) are poorly understood. 25682038 1 68 theme renal 174:178 arg1 failure 180:186 chronic renal failure 166:186 chronic renal failure (CRF) 166:192 OBJECTIVE The pathogenic events responsible for accelerated atherosclerosis in patients with chronic renal failure (CRF) are poorly understood. 25682038 4 69 theme controls 713:720 arg1 controls 713:720 their controls 707:720 their controls 707:720 Randomized groups of 5/6 nephrectomized mice and their controls were also injected i.p. with a SOD/catalase mimetic (MnTBAP) for 15 days starting immediately after the final surgical procedure. 25682038 4 69 theme controls 713:720 arg1 groups 669:674 Randomized groups 658:674 Randomized groups of 5/6 nephrectomized mice and their controls 658:720 Randomized groups of 5/6 nephrectomized mice and their controls were also injected i.p. with a SOD/catalase mimetic (MnTBAP) for 15 days starting immediately after the final surgical procedure. 25682038 4 69 theme controls 713:720 arg1 mice 698:701 5/6 nephrectomized mice 679:701 5/6 nephrectomized mice 679:701 Randomized groups of 5/6 nephrectomized mice and their controls were also injected i.p. with a SOD/catalase mimetic (MnTBAP) for 15 days starting immediately after the final surgical procedure. 25682038 2 70 from production 318:327 arg1 adipocytes 332:341 adipocytes 332:341 adipocytes 332:341 Here we investigate the hypothesis that concentrations of urea associated with CRF and increased ROS production in adipocytes might also increase ROS production directly in arterial endothelial cells, causing the same pathophysiologic changes seen with hyperglycemia. 25682038 7 71 theme Urea-induced 1232:1243 arg1 ROS 1245:1247 Urea-induced ROS 1232:1247 Urea-induced ROS 1232:1247 Urea-induced ROS directly inactivated the anti-atherosclerosis enzyme PGI2 synthase and also caused ER stress. 25682038 9 72 theme increased 1540:1548 arg1 expression 1550:1559 increased expression 1540:1559 increased expression of the pro-inflammatory proteins TNFα, IL-6, VCAM1, Endoglin, and MCP-1 1540:1631 In uremic mice, treatment with MnTBAP prevented aortic oxidative stress, PGI2 synthase activity reduction and increased expression of the pro-inflammatory proteins TNFα, IL-6, VCAM1, Endoglin, and MCP-1. 25682038 6 73 theme increased 1119:1127 arg1 activity 1148:1155 increased hexosamine pathway activity 1119:1155 increased hexosamine pathway activity 1119:1155 Urea-induced ROS caused the activation of endothelial pro-inflammatory pathways through the inhibition of GAPDH, including increased protein kinase C isoforms activity, increased hexosamine pathway activity, and accumulation of intracellular AGEs (advanced glycation end products). 25682038 8 74 theme urea 1424:1427 arg1 effects 1413:1419 these effects 1407:1419 these effects of urea 1407:1427 Normalization of mitochondrial ROS production prevented each of these effects of urea. 25682038 1 75 theme pathogenic 87:96 arg1 events 98:103 The pathogenic events 83:103 The pathogenic events responsible for accelerated atherosclerosis in patients with chronic renal failure (CRF) 83:192 OBJECTIVE The pathogenic events responsible for accelerated atherosclerosis in patients with chronic renal failure (CRF) are poorly understood. 25682038 2 76 theme arterial 390:397 arg1 cells 411:415 arterial endothelial cells 390:415 arterial endothelial cells 390:415 Here we investigate the hypothesis that concentrations of urea associated with CRF and increased ROS production in adipocytes might also increase ROS production directly in arterial endothelial cells, causing the same pathophysiologic changes seen with hyperglycemia. 25682038 0 77 theme endothelial 23:33 arg1 dysfunction 35:45 endothelial dysfunction 23:45 endothelial dysfunction in chronic renal failure 23:70 Urea-induced ROS cause endothelial dysfunction in chronic renal failure. 25682038 1 78 from atherosclerosis 133:147 arg1 patients 152:159 patients 152:159 patients with chronic renal failure (CRF) 152:192 OBJECTIVE The pathogenic events responsible for accelerated atherosclerosis in patients with chronic renal failure (CRF) are poorly understood. 25682038 1 79 theme responsible 105:115 arg1 events 98:103 The pathogenic events 83:103 The pathogenic events responsible for accelerated atherosclerosis in patients with chronic renal failure (CRF) 83:192 OBJECTIVE The pathogenic events responsible for accelerated atherosclerosis in patients with chronic renal failure (CRF) are poorly understood. 25682038 6 80 theme C 1098:1098 arg1 isoforms 1100:1107 protein kinase C isoforms 1083:1107 increased protein kinase C isoforms activity 1073:1116 Urea-induced ROS caused the activation of endothelial pro-inflammatory pathways through the inhibition of GAPDH, including increased protein kinase C isoforms activity, increased hexosamine pathway activity, and accumulation of intracellular AGEs (advanced glycation end products). 25682038 4 81 theme mimetic 766:772 arg1 SOD/catalase 753:764 a SOD/catalase 751:764 a SOD/catalase mimetic (MnTBAP) 751:781 Randomized groups of 5/6 nephrectomized mice and their controls were also injected i.p. with a SOD/catalase mimetic (MnTBAP) for 15 days starting immediately after the final surgical procedure. 25682038 2 82 theme same 430:433 arg1 changes 452:458 the same pathophysiologic changes 426:458 the same pathophysiologic changes seen with hyperglycemia 426:482 Here we investigate the hypothesis that concentrations of urea associated with CRF and increased ROS production in adipocytes might also increase ROS production directly in arterial endothelial cells, causing the same pathophysiologic changes seen with hyperglycemia. 25682038 6 83 theme protein 1083:1089 arg1 C 1098:1098 protein kinase C 1083:1098 increased protein kinase C isoforms activity 1073:1116 Urea-induced ROS caused the activation of endothelial pro-inflammatory pathways through the inhibition of GAPDH, including increased protein kinase C isoforms activity, increased hexosamine pathway activity, and accumulation of intracellular AGEs (advanced glycation end products). 25682038 0 84 theme renal 58:62 arg1 failure 64:70 chronic renal failure 50:70 chronic renal failure 50:70 Urea-induced ROS cause endothelial dysfunction in chronic renal failure. 25682038 9 85 theme uremic 1433:1438 arg1 mice 1440:1443 uremic mice 1433:1443 uremic mice 1433:1443 In uremic mice, treatment with MnTBAP prevented aortic oxidative stress, PGI2 synthase activity reduction and increased expression of the pro-inflammatory proteins TNFα, IL-6, VCAM1, Endoglin, and MCP-1. 25682038 6 86 theme intracellular 1178:1190 arg1 products 1221:1228 advanced glycation end products 1198:1228 advanced glycation end products 1198:1228 Urea-induced ROS caused the activation of endothelial pro-inflammatory pathways through the inhibition of GAPDH, including increased protein kinase C isoforms activity, increased hexosamine pathway activity, and accumulation of intracellular AGEs (advanced glycation end products). 25682038 6 86 theme intracellular 1178:1190 arg1 AGEs 1192:1195 intracellular AGEs 1178:1195 intracellular AGEs (advanced glycation end products) 1178:1229 Urea-induced ROS caused the activation of endothelial pro-inflammatory pathways through the inhibition of GAPDH, including increased protein kinase C isoforms activity, increased hexosamine pathway activity, and accumulation of intracellular AGEs (advanced glycation end products). 25682038 4 87 theme surgical 832:839 arg1 procedure 841:849 the final surgical procedure 822:849 the final surgical procedure 822:849 Randomized groups of 5/6 nephrectomized mice and their controls were also injected i.p. with a SOD/catalase mimetic (MnTBAP) for 15 days starting immediately after the final surgical procedure. 25682038 3 88 theme endothelial 526:536 arg1 HAEC 545:548 HAEC 545:548 HAEC 545:548 METHODS Primary cultures of human aortic endothelial cells (HAEC) were exposed to 20mM urea for 48 h. C57BL/6J wild-type mice underwent 5/6 nephrectomy or a sham operation. 25682038 3 88 theme endothelial 526:536 arg1 cells 538:542 human aortic endothelial cells 513:542 human aortic endothelial cells (HAEC) 513:549 METHODS Primary cultures of human aortic endothelial cells (HAEC) were exposed to 20mM urea for 48 h. C57BL/6J wild-type mice underwent 5/6 nephrectomy or a sham operation. 25682038 7 89 theme ER 1332:1333 arg1 stress 1335:1340 ER stress 1332:1340 ER stress 1332:1340 Urea-induced ROS directly inactivated the anti-atherosclerosis enzyme PGI2 synthase and also caused ER stress. 25682038 3 90 theme human 513:517 arg1 HAEC 545:548 HAEC 545:548 HAEC 545:548 METHODS Primary cultures of human aortic endothelial cells (HAEC) were exposed to 20mM urea for 48 h. C57BL/6J wild-type mice underwent 5/6 nephrectomy or a sham operation. 25682038 3 90 theme human 513:517 arg1 cells 538:542 human aortic endothelial cells 513:542 human aortic endothelial cells (HAEC) 513:549 METHODS Primary cultures of human aortic endothelial cells (HAEC) were exposed to 20mM urea for 48 h. C57BL/6J wild-type mice underwent 5/6 nephrectomy or a sham operation. 25682038 9 91 with treatment 1446:1454 arg1 MnTBAP 1461:1466 MnTBAP 1461:1466 MnTBAP 1461:1466 In uremic mice, treatment with MnTBAP prevented aortic oxidative stress, PGI2 synthase activity reduction and increased expression of the pro-inflammatory proteins TNFα, IL-6, VCAM1, Endoglin, and MCP-1. 28808112 7 0 theme regulatory 1165:1174 arg1 mechanism 1176:1184 a post-translational regulatory mechanism 1144:1184 a post-translational regulatory mechanism essential for maintaining perforin in an inactive state until its secretion from the inhibitory acidic environment of the secretory granule 1144:1324 In sum, our studies reveal a post-translational regulatory mechanism essential for maintaining perforin in an inactive state until its secretion from the inhibitory acidic environment of the secretory granule. 28808112 4 1 gly glycosylation 557:569 arg1 Asn549 601:606 Asn549 601:606 Asn549 within the endoplasmic reticulum 601:639 Here, we show that N-linked glycosylation of the perforin C-terminus at Asn549 within the endoplasmic reticulum inhibits oligomerisation of perforin monomers and thus protects the host cell from premature pore formation. 28808112 4 1 gly glycosylation 557:569 arg2 Asn549 601:606 Asn549 601:606 Asn549 within the endoplasmic reticulum 601:639 Here, we show that N-linked glycosylation of the perforin C-terminus at Asn549 within the endoplasmic reticulum inhibits oligomerisation of perforin monomers and thus protects the host cell from premature pore formation. 28808112 4 1 gly glycosylation 557:569 arg1 C-terminus 587:596 the perforin C-terminus 574:596 the perforin C-terminus 574:596 Here, we show that N-linked glycosylation of the perforin C-terminus at Asn549 within the endoplasmic reticulum inhibits oligomerisation of perforin monomers and thus protects the host cell from premature pore formation. 28808112 4 2 theme pore 734:737 arg1 formation 739:747 premature pore formation 724:747 premature pore formation 724:747 Here, we show that N-linked glycosylation of the perforin C-terminus at Asn549 within the endoplasmic reticulum inhibits oligomerisation of perforin monomers and thus protects the host cell from premature pore formation. 28808112 6 3 theme unstructured 1070:1081 arg1 nature 1095:1100 the unstructured and exposed nature 1066:1100 the unstructured and exposed nature of the region 1066:1114 Despite evolutionary conservation of the C-terminus, we found that processing is carried out by multiple proteases, which we attribute to the unstructured and exposed nature of the region. 28808112 1 4 theme cytotoxic 183:191 arg1 lymphocytes 193:203 cytotoxic lymphocytes 183:203 cytotoxic lymphocytes 183:203 Perforin is a highly cytotoxic pore-forming protein essential for immune surveillance by cytotoxic lymphocytes. 28808112 6 5 theme C-terminus 969:978 arg1 conservation 949:960 evolutionary conservation 936:960 evolutionary conservation of the C-terminus 936:978 Despite evolutionary conservation of the C-terminus, we found that processing is carried out by multiple proteases, which we attribute to the unstructured and exposed nature of the region. 28808112 7 6 theme post-translational 1146:1163 arg1 mechanism 1176:1184 a post-translational regulatory mechanism 1144:1184 a post-translational regulatory mechanism essential for maintaining perforin in an inactive state until its secretion from the inhibitory acidic environment of the secretory granule 1144:1324 In sum, our studies reveal a post-translational regulatory mechanism essential for maintaining perforin in an inactive state until its secretion from the inhibitory acidic environment of the secretory granule. 28808112 4 7 theme premature 724:732 arg1 formation 739:747 premature pore formation 724:747 premature pore formation 724:747 Here, we show that N-linked glycosylation of the perforin C-terminus at Asn549 within the endoplasmic reticulum inhibits oligomerisation of perforin monomers and thus protects the host cell from premature pore formation. 28808112 4 8 link N-linked 548:555 arg1 glycosylation 557:569 N-linked glycosylation 548:569 N-linked glycosylation of the perforin C-terminus at Asn549 within the endoplasmic reticulum 548:639 Here, we show that N-linked glycosylation of the perforin C-terminus at Asn549 within the endoplasmic reticulum inhibits oligomerisation of perforin monomers and thus protects the host cell from premature pore formation. 28808112 5 9 theme perforin 888:895 arg1 activation 897:906 perforin activation 888:906 perforin activation prior to secretion 888:925 Subsequent removal of this glycan occurs through proteolytic processing of the C-terminus within secretory granules and is imperative for perforin activation prior to secretion. 28808112 3 10 theme secretory 439:447 arg1 granules 449:456 secretory granules 439:456 secretory granules 439:456 However, how cytotoxic lymphocytes remain protected from their own perforin prior to its export to secretory granules, particularly in the Ca2+-rich endoplasmic reticulum, remains unknown. 28808112 4 11 theme perforin 669:676 arg1 monomers 678:685 perforin monomers 669:685 perforin monomers 669:685 Here, we show that N-linked glycosylation of the perforin C-terminus at Asn549 within the endoplasmic reticulum inhibits oligomerisation of perforin monomers and thus protects the host cell from premature pore formation. 28808112 2 12 theme secretory 284:292 arg1 granules 294:301 acidic secretory granules 277:301 acidic secretory granules where it remains functionally inert 277:337 Prior to delivery to target cells by exocytosis, perforin is stored in acidic secretory granules where it remains functionally inert. 28808112 4 13 from Asn549 601:606 arg1 glycosylation 557:569 N-linked glycosylation 548:569 N-linked glycosylation of the perforin C-terminus at Asn549 within the endoplasmic reticulum 548:639 Here, we show that N-linked glycosylation of the perforin C-terminus at Asn549 within the endoplasmic reticulum inhibits oligomerisation of perforin monomers and thus protects the host cell from premature pore formation. 28808112 7 14 theme inactive 1227:1234 arg1 state 1236:1240 an inactive state 1224:1240 an inactive state until its secretion from the inhibitory acidic environment of the secretory granule 1224:1324 In sum, our studies reveal a post-translational regulatory mechanism essential for maintaining perforin in an inactive state until its secretion from the inhibitory acidic environment of the secretory granule. 28808112 6 15 theme evolutionary 936:947 arg1 conservation 949:960 evolutionary conservation 936:960 evolutionary conservation of the C-terminus 936:978 Despite evolutionary conservation of the C-terminus, we found that processing is carried out by multiple proteases, which we attribute to the unstructured and exposed nature of the region. 28808112 7 16 theme inhibitory 1271:1280 arg1 environment 1289:1299 the inhibitory acidic environment 1267:1299 the inhibitory acidic environment of the secretory granule 1267:1324 In sum, our studies reveal a post-translational regulatory mechanism essential for maintaining perforin in an inactive state until its secretion from the inhibitory acidic environment of the secretory granule. 28808112 4 17 theme host 709:712 arg1 cell 714:717 the host cell 705:717 the host cell 705:717 Here, we show that N-linked glycosylation of the perforin C-terminus at Asn549 within the endoplasmic reticulum inhibits oligomerisation of perforin monomers and thus protects the host cell from premature pore formation. 28808112 3 18 theme prior 416:420 arg1 perforin 407:414 their own perforin 397:414 their own perforin prior to its export to secretory granules, particularly in the Ca2+-rich endoplasmic reticulum, 397:510 However, how cytotoxic lymphocytes remain protected from their own perforin prior to its export to secretory granules, particularly in the Ca2+-rich endoplasmic reticulum, remains unknown. 28808112 7 19 from environment 1289:1299 arg1 secretion 1252:1260 its secretion 1248:1260 its secretion from the inhibitory acidic environment of the secretory granule 1248:1324 In sum, our studies reveal a post-translational regulatory mechanism essential for maintaining perforin in an inactive state until its secretion from the inhibitory acidic environment of the secretory granule. 28808112 6 20 theme region 1109:1114 arg1 nature 1095:1100 the unstructured and exposed nature 1066:1100 the unstructured and exposed nature of the region 1066:1114 Despite evolutionary conservation of the C-terminus, we found that processing is carried out by multiple proteases, which we attribute to the unstructured and exposed nature of the region. 28808112 0 21 theme activation 23:32 arg1 Regulation 0:9 Regulation 0:9 Regulation of perforin activation 0:32 Regulation of perforin activation and pre-synaptic toxicity through C-terminal glycosylation. 28808112 0 21 theme activation 23:32 arg1 toxicity 51:58 pre-synaptic toxicity 38:58 pre-synaptic toxicity through C-terminal glycosylation 38:91 Regulation of perforin activation and pre-synaptic toxicity through C-terminal glycosylation. 28808112 6 22 theme multiple 1024:1031 arg1 proteases 1033:1041 multiple proteases 1024:1041 multiple proteases 1024:1041 Despite evolutionary conservation of the C-terminus, we found that processing is carried out by multiple proteases, which we attribute to the unstructured and exposed nature of the region. 28808112 3 23 theme Ca2+-rich 479:487 arg1 reticulum 501:509 the Ca2+-rich endoplasmic reticulum 475:509 the Ca2+-rich endoplasmic reticulum 475:509 However, how cytotoxic lymphocytes remain protected from their own perforin prior to its export to secretory granules, particularly in the Ca2+-rich endoplasmic reticulum, remains unknown. 28808112 3 24 theme own 403:405 arg1 perforin 407:414 their own perforin 397:414 their own perforin prior to its export to secretory granules, particularly in the Ca2+-rich endoplasmic reticulum, 397:510 However, how cytotoxic lymphocytes remain protected from their own perforin prior to its export to secretory granules, particularly in the Ca2+-rich endoplasmic reticulum, remains unknown. 28808112 4 25 theme C-terminus 587:596 arg1 glycosylation 557:569 N-linked glycosylation 548:569 N-linked glycosylation of the perforin C-terminus at Asn549 within the endoplasmic reticulum 548:639 Here, we show that N-linked glycosylation of the perforin C-terminus at Asn549 within the endoplasmic reticulum inhibits oligomerisation of perforin monomers and thus protects the host cell from premature pore formation. 28808112 1 26 theme cytotoxic 115:123 arg1 Perforin 94:101 Perforin 94:101 Perforin 94:101 Perforin is a highly cytotoxic pore-forming protein essential for immune surveillance by cytotoxic lymphocytes. 28808112 1 26 theme cytotoxic 115:123 arg1 protein 138:144 a highly cytotoxic pore-forming protein 106:144 a highly cytotoxic pore-forming protein essential for immune surveillance by cytotoxic lymphocytes 106:203 Perforin is a highly cytotoxic pore-forming protein essential for immune surveillance by cytotoxic lymphocytes. 28808112 3 27 theme endoplasmic 489:499 arg1 reticulum 501:509 the Ca2+-rich endoplasmic reticulum 475:509 the Ca2+-rich endoplasmic reticulum 475:509 However, how cytotoxic lymphocytes remain protected from their own perforin prior to its export to secretory granules, particularly in the Ca2+-rich endoplasmic reticulum, remains unknown. 28808112 0 28 theme pre-synaptic 38:49 arg1 toxicity 51:58 pre-synaptic toxicity 38:58 pre-synaptic toxicity through C-terminal glycosylation 38:91 Regulation of perforin activation and pre-synaptic toxicity through C-terminal glycosylation. 28808112 4 29 theme perforin 578:585 arg1 C-terminus 587:596 the perforin C-terminus 574:596 the perforin C-terminus 574:596 Here, we show that N-linked glycosylation of the perforin C-terminus at Asn549 within the endoplasmic reticulum inhibits oligomerisation of perforin monomers and thus protects the host cell from premature pore formation. 28808112 5 30 theme Subsequent 750:759 arg1 removal 761:767 Subsequent removal 750:767 Subsequent removal of this glycan 750:782 Subsequent removal of this glycan occurs through proteolytic processing of the C-terminus within secretory granules and is imperative for perforin activation prior to secretion. 28808112 7 31 theme secretory 1308:1316 arg1 granule 1318:1324 the secretory granule 1304:1324 the secretory granule 1304:1324 In sum, our studies reveal a post-translational regulatory mechanism essential for maintaining perforin in an inactive state until its secretion from the inhibitory acidic environment of the secretory granule. 28808112 5 32 theme C-terminus 829:838 arg1 processing 811:820 proteolytic processing 799:820 proteolytic processing of the C-terminus 799:838 Subsequent removal of this glycan occurs through proteolytic processing of the C-terminus within secretory granules and is imperative for perforin activation prior to secretion. 28808112 4 33 theme monomers 678:685 arg1 oligomerisation 650:664 oligomerisation 650:664 oligomerisation of perforin monomers 650:685 Here, we show that N-linked glycosylation of the perforin C-terminus at Asn549 within the endoplasmic reticulum inhibits oligomerisation of perforin monomers and thus protects the host cell from premature pore formation. 28808112 7 34 theme essential 1186:1194 arg1 mechanism 1176:1184 a post-translational regulatory mechanism 1144:1184 a post-translational regulatory mechanism essential for maintaining perforin in an inactive state until its secretion from the inhibitory acidic environment of the secretory granule 1144:1324 In sum, our studies reveal a post-translational regulatory mechanism essential for maintaining perforin in an inactive state until its secretion from the inhibitory acidic environment of the secretory granule. 28808112 6 35 theme exposed 1087:1093 arg1 nature 1095:1100 the unstructured and exposed nature 1066:1100 the unstructured and exposed nature of the region 1066:1114 Despite evolutionary conservation of the C-terminus, we found that processing is carried out by multiple proteases, which we attribute to the unstructured and exposed nature of the region. 28808112 0 36 theme C-terminal 68:77 arg1 glycosylation 79:91 C-terminal glycosylation 68:91 C-terminal glycosylation 68:91 Regulation of perforin activation and pre-synaptic toxicity through C-terminal glycosylation. 28808112 1 37 theme pore-forming 125:136 arg1 Perforin 94:101 Perforin 94:101 Perforin 94:101 Perforin is a highly cytotoxic pore-forming protein essential for immune surveillance by cytotoxic lymphocytes. 28808112 1 37 theme pore-forming 125:136 arg1 protein 138:144 a highly cytotoxic pore-forming protein 106:144 a highly cytotoxic pore-forming protein essential for immune surveillance by cytotoxic lymphocytes 106:203 Perforin is a highly cytotoxic pore-forming protein essential for immune surveillance by cytotoxic lymphocytes. 28808112 5 38 theme secretory 847:855 arg1 granules 857:864 secretory granules 847:864 secretory granules 847:864 Subsequent removal of this glycan occurs through proteolytic processing of the C-terminus within secretory granules and is imperative for perforin activation prior to secretion. 28808112 4 39 theme N-linked 548:555 arg1 glycosylation 557:569 N-linked glycosylation 548:569 N-linked glycosylation of the perforin C-terminus at Asn549 within the endoplasmic reticulum 548:639 Here, we show that N-linked glycosylation of the perforin C-terminus at Asn549 within the endoplasmic reticulum inhibits oligomerisation of perforin monomers and thus protects the host cell from premature pore formation. 28808112 2 40 theme target 227:232 arg1 cells 234:238 target cells 227:238 target cells 227:238 Prior to delivery to target cells by exocytosis, perforin is stored in acidic secretory granules where it remains functionally inert. 28808112 2 41 theme acidic 277:282 arg1 granules 294:301 acidic secretory granules 277:301 acidic secretory granules where it remains functionally inert 277:337 Prior to delivery to target cells by exocytosis, perforin is stored in acidic secretory granules where it remains functionally inert. 28808112 5 42 theme proteolytic 799:809 arg1 processing 811:820 proteolytic processing 799:820 proteolytic processing of the C-terminus 799:838 Subsequent removal of this glycan occurs through proteolytic processing of the C-terminus within secretory granules and is imperative for perforin activation prior to secretion. 28808112 1 43 theme essential 146:154 arg1 Perforin 94:101 Perforin 94:101 Perforin 94:101 Perforin is a highly cytotoxic pore-forming protein essential for immune surveillance by cytotoxic lymphocytes. 28808112 1 43 theme essential 146:154 arg1 protein 138:144 a highly cytotoxic pore-forming protein 106:144 a highly cytotoxic pore-forming protein essential for immune surveillance by cytotoxic lymphocytes 106:203 Perforin is a highly cytotoxic pore-forming protein essential for immune surveillance by cytotoxic lymphocytes. 28808112 5 44 theme glycan 777:782 arg1 removal 761:767 Subsequent removal 750:767 Subsequent removal of this glycan 750:782 Subsequent removal of this glycan occurs through proteolytic processing of the C-terminus within secretory granules and is imperative for perforin activation prior to secretion. 28808112 4 45 theme endoplasmic 619:629 arg1 reticulum 631:639 the endoplasmic reticulum 615:639 the endoplasmic reticulum 615:639 Here, we show that N-linked glycosylation of the perforin C-terminus at Asn549 within the endoplasmic reticulum inhibits oligomerisation of perforin monomers and thus protects the host cell from premature pore formation. 28808112 7 46 theme acidic 1282:1287 arg1 environment 1289:1299 the inhibitory acidic environment 1267:1299 the inhibitory acidic environment of the secretory granule 1267:1324 In sum, our studies reveal a post-translational regulatory mechanism essential for maintaining perforin in an inactive state until its secretion from the inhibitory acidic environment of the secretory granule. 28808112 5 47 theme prior 908:912 arg1 activation 897:906 perforin activation 888:906 perforin activation prior to secretion 888:925 Subsequent removal of this glycan occurs through proteolytic processing of the C-terminus within secretory granules and is imperative for perforin activation prior to secretion. 28808112 3 48 from granules 449:456 arg1 reticulum 501:509 the Ca2+-rich endoplasmic reticulum 475:509 the Ca2+-rich endoplasmic reticulum 475:509 However, how cytotoxic lymphocytes remain protected from their own perforin prior to its export to secretory granules, particularly in the Ca2+-rich endoplasmic reticulum, remains unknown. 28808112 1 49 theme immune 160:165 arg1 surveillance 167:178 immune surveillance 160:178 immune surveillance by cytotoxic lymphocytes 160:203 Perforin is a highly cytotoxic pore-forming protein essential for immune surveillance by cytotoxic lymphocytes. 28808112 3 50 theme cytotoxic 353:361 arg1 lymphocytes 363:373 cytotoxic lymphocytes 353:373 cytotoxic lymphocytes 353:373 However, how cytotoxic lymphocytes remain protected from their own perforin prior to its export to secretory granules, particularly in the Ca2+-rich endoplasmic reticulum, remains unknown. 28808112 0 51 theme perforin 14:21 arg1 activation 23:32 perforin activation 14:32 perforin activation 14:32 Regulation of perforin activation and pre-synaptic toxicity through C-terminal glycosylation. 28808112 7 52 theme granule 1318:1324 arg1 environment 1289:1299 the inhibitory acidic environment 1267:1299 the inhibitory acidic environment of the secretory granule 1267:1324 In sum, our studies reveal a post-translational regulatory mechanism essential for maintaining perforin in an inactive state until its secretion from the inhibitory acidic environment of the secretory granule. 28161794 5 0 theme TLR6ED 730:735 arg1 modules 808:814 TLR6ED with secondary structure contents similar to leucine-rich repeat (LRR) modules 730:814 TLR6ED with secondary structure contents similar to leucine-rich repeat (LRR) modules 730:814 Circular dichroism (CD) experiments confirmed the structural formation of TLR6ED with secondary structure contents similar to leucine-rich repeat (LRR) modules. 28161794 6 1 theme modifications 979:991 arg1 preservation 936:947 preservation 936:947 preservation of some key posttranslational modifications often lacking in bacteria-expressed proteins 936:1036 In addition, we also provided a procedure for preparing this recombinant protein using Sf9 insect cells, which ensures preservation of some key posttranslational modifications often lacking in bacteria-expressed proteins. 28161794 7 2 with effects 1214:1220 arg1 TLR4 1189:1192 TLR4 1189:1192 TLR4 1189:1192 These materials would be useful for analyzing novel molecules that bind directly to TLR6, complex formations with other regulators including TLR2 and TLR4, and the functional effects of N-linked glycosylation. 28161794 7 2 with effects 1214:1220 arg1 TLR2 1180:1183 TLR2 1180:1183 TLR2 1180:1183 These materials would be useful for analyzing novel molecules that bind directly to TLR6, complex formations with other regulators including TLR2 and TLR4, and the functional effects of N-linked glycosylation. 28161794 7 2 with effects 1214:1220 arg1 regulators 1159:1168 other regulators 1153:1168 other regulators including TLR2 and TLR4 1153:1192 These materials would be useful for analyzing novel molecules that bind directly to TLR6, complex formations with other regulators including TLR2 and TLR4, and the functional effects of N-linked glycosylation. 28161794 6 3 theme key 957:959 arg1 modifications 979:991 some key posttranslational modifications 952:991 some key posttranslational modifications often lacking in bacteria-expressed proteins 952:1036 In addition, we also provided a procedure for preparing this recombinant protein using Sf9 insect cells, which ensures preservation of some key posttranslational modifications often lacking in bacteria-expressed proteins. 28161794 3 4 from coli 462:465 arg1 receptor 427:434 human Toll-like receptor 6 411:436 human Toll-like receptor 6 (TLR6ED) in Escherichia coli 411:465 In this study, we propose an efficient method for preparation of the extracellular domain of human Toll-like receptor 6 (TLR6ED) in Escherichia coli using the bubbling cultivation method. 28161794 3 4 from coli 462:465 arg1 domain 401:406 the extracellular domain 383:406 the extracellular domain of human Toll-like receptor 6 (TLR6ED) in Escherichia coli 383:465 In this study, we propose an efficient method for preparation of the extracellular domain of human Toll-like receptor 6 (TLR6ED) in Escherichia coli using the bubbling cultivation method. 28161794 6 5 theme bacteria-expressed 1010:1027 arg1 proteins 1029:1036 bacteria-expressed proteins 1010:1036 bacteria-expressed proteins 1010:1036 In addition, we also provided a procedure for preparing this recombinant protein using Sf9 insect cells, which ensures preservation of some key posttranslational modifications often lacking in bacteria-expressed proteins. 28161794 7 6 with formations 1137:1146 arg1 TLR4 1189:1192 TLR4 1189:1192 TLR4 1189:1192 These materials would be useful for analyzing novel molecules that bind directly to TLR6, complex formations with other regulators including TLR2 and TLR4, and the functional effects of N-linked glycosylation. 28161794 7 6 with formations 1137:1146 arg1 TLR2 1180:1183 TLR2 1180:1183 TLR2 1180:1183 These materials would be useful for analyzing novel molecules that bind directly to TLR6, complex formations with other regulators including TLR2 and TLR4, and the functional effects of N-linked glycosylation. 28161794 7 6 with formations 1137:1146 arg1 regulators 1159:1168 other regulators 1153:1168 other regulators including TLR2 and TLR4 1153:1192 These materials would be useful for analyzing novel molecules that bind directly to TLR6, complex formations with other regulators including TLR2 and TLR4, and the functional effects of N-linked glycosylation. 28161794 7 7 with TLR6 1123:1126 arg1 TLR4 1189:1192 TLR4 1189:1192 TLR4 1189:1192 These materials would be useful for analyzing novel molecules that bind directly to TLR6, complex formations with other regulators including TLR2 and TLR4, and the functional effects of N-linked glycosylation. 28161794 7 7 with TLR6 1123:1126 arg1 TLR2 1180:1183 TLR2 1180:1183 TLR2 1180:1183 These materials would be useful for analyzing novel molecules that bind directly to TLR6, complex formations with other regulators including TLR2 and TLR4, and the functional effects of N-linked glycosylation. 28161794 7 7 with TLR6 1123:1126 arg1 regulators 1159:1168 other regulators 1153:1168 other regulators including TLR2 and TLR4 1153:1192 These materials would be useful for analyzing novel molecules that bind directly to TLR6, complex formations with other regulators including TLR2 and TLR4, and the functional effects of N-linked glycosylation. 28161794 4 8 theme expression 551:560 arg1 level 542:546 the level 538:546 the level of expression of TLR6ED into a soluble fraction 538:594 Our preparation method improved the level of expression of TLR6ED into a soluble fraction as compared with typical cultivation using a rotary shaker. 28161794 2 9 theme novel 248:252 arg1 ligands 254:260 novel ligands 248:260 novel ligands 248:260 To further elucidate the function of TLRs, it is important to identify novel ligands and their action mechanisms including polymer assembly. 28161794 2 9 theme novel 248:252 arg1 assembly 308:315 polymer assembly 300:315 polymer assembly 300:315 To further elucidate the function of TLRs, it is important to identify novel ligands and their action mechanisms including polymer assembly. 28161794 1 10 theme ligands 168:174 arg1 ligands 168:174 ligands 168:174 ligands 168:174 Toll-like receptors (TLRs) mediate immune responses upon recognition of a variety of ligands. 28161794 1 10 theme ligands 168:174 arg1 variety 157:163 a variety 155:163 a variety of ligands 155:174 Toll-like receptors (TLRs) mediate immune responses upon recognition of a variety of ligands. 28161794 1 11 theme variety 157:163 arg1 recognition 140:150 recognition 140:150 recognition of a variety of ligands 140:174 Toll-like receptors (TLRs) mediate immune responses upon recognition of a variety of ligands. 28161794 5 12 theme structural 706:715 arg1 formation 717:725 the structural formation 702:725 the structural formation of TLR6ED with secondary structure contents similar to leucine-rich repeat (LRR) modules 702:814 Circular dichroism (CD) experiments confirmed the structural formation of TLR6ED with secondary structure contents similar to leucine-rich repeat (LRR) modules. 28161794 7 13 theme novel 1085:1089 arg1 molecules 1091:1099 novel molecules 1085:1099 novel molecules that bind directly to TLR6, complex formations with other regulators including TLR2 and TLR4, and the functional effects of N-linked glycosylation 1085:1246 These materials would be useful for analyzing novel molecules that bind directly to TLR6, complex formations with other regulators including TLR2 and TLR4, and the functional effects of N-linked glycosylation. 28161794 3 14 theme human 411:415 arg1 receptor 427:434 human Toll-like receptor 6 411:436 human Toll-like receptor 6 (TLR6ED) in Escherichia coli 411:465 In this study, we propose an efficient method for preparation of the extracellular domain of human Toll-like receptor 6 (TLR6ED) in Escherichia coli using the bubbling cultivation method. 28161794 3 14 theme human 411:415 arg1 TLR6ED 439:444 TLR6ED 439:444 TLR6ED 439:444 In this study, we propose an efficient method for preparation of the extracellular domain of human Toll-like receptor 6 (TLR6ED) in Escherichia coli using the bubbling cultivation method. 28161794 3 15 theme efficient 347:355 arg1 method 357:362 an efficient method 344:362 an efficient method for preparation of the extracellular domain of human Toll-like receptor 6 (TLR6ED) in Escherichia coli using the bubbling cultivation method 344:503 In this study, we propose an efficient method for preparation of the extracellular domain of human Toll-like receptor 6 (TLR6ED) in Escherichia coli using the bubbling cultivation method. 28161794 1 16 theme Toll-like 83:91 arg1 receptors 93:101 Toll-like receptors 83:101 Toll-like receptors (TLRs) 83:108 Toll-like receptors (TLRs) mediate immune responses upon recognition of a variety of ligands. 28161794 1 16 theme Toll-like 83:91 arg1 TLRs 104:107 TLRs 104:107 TLRs 104:107 Toll-like receptors (TLRs) mediate immune responses upon recognition of a variety of ligands. 28161794 7 17 theme other 1153:1157 arg1 TLR4 1189:1192 TLR4 1189:1192 TLR4 1189:1192 These materials would be useful for analyzing novel molecules that bind directly to TLR6, complex formations with other regulators including TLR2 and TLR4, and the functional effects of N-linked glycosylation. 28161794 7 17 theme other 1153:1157 arg1 TLR2 1180:1183 TLR2 1180:1183 TLR2 1180:1183 These materials would be useful for analyzing novel molecules that bind directly to TLR6, complex formations with other regulators including TLR2 and TLR4, and the functional effects of N-linked glycosylation. 28161794 7 17 theme other 1153:1157 arg1 regulators 1159:1168 other regulators 1153:1168 other regulators including TLR2 and TLR4 1153:1192 These materials would be useful for analyzing novel molecules that bind directly to TLR6, complex formations with other regulators including TLR2 and TLR4, and the functional effects of N-linked glycosylation. 28161794 3 18 theme extracellular 387:399 arg1 receptor 427:434 human Toll-like receptor 6 411:436 human Toll-like receptor 6 (TLR6ED) in Escherichia coli 411:465 In this study, we propose an efficient method for preparation of the extracellular domain of human Toll-like receptor 6 (TLR6ED) in Escherichia coli using the bubbling cultivation method. 28161794 3 18 theme extracellular 387:399 arg1 domain 401:406 the extracellular domain 383:406 the extracellular domain of human Toll-like receptor 6 (TLR6ED) in Escherichia coli 383:465 In this study, we propose an efficient method for preparation of the extracellular domain of human Toll-like receptor 6 (TLR6ED) in Escherichia coli using the bubbling cultivation method. 28161794 5 19 theme leucine-rich 782:793 arg1 LRR 803:805 LRR 803:805 LRR 803:805 Circular dichroism (CD) experiments confirmed the structural formation of TLR6ED with secondary structure contents similar to leucine-rich repeat (LRR) modules. 28161794 5 19 theme leucine-rich 782:793 arg1 repeat 795:800 leucine-rich repeat 782:800 leucine-rich repeat (LRR) 782:806 Circular dichroism (CD) experiments confirmed the structural formation of TLR6ED with secondary structure contents similar to leucine-rich repeat (LRR) modules. 28161794 7 20 theme complex 1129:1135 arg1 formations 1137:1146 complex formations 1129:1146 complex formations with other regulators including TLR2 and TLR4 1129:1192 These materials would be useful for analyzing novel molecules that bind directly to TLR6, complex formations with other regulators including TLR2 and TLR4, and the functional effects of N-linked glycosylation. 28161794 3 21 theme domain 401:406 arg1 preparation 368:378 preparation 368:378 preparation of the extracellular domain of human Toll-like receptor 6 (TLR6ED) in Escherichia coli using the bubbling cultivation method 368:503 In this study, we propose an efficient method for preparation of the extracellular domain of human Toll-like receptor 6 (TLR6ED) in Escherichia coli using the bubbling cultivation method. 28161794 0 22 theme Extracellular 19:31 arg1 Receptor 71:78 Recombinant Human Toll-like Receptor 6 43:80 Recombinant Human Toll-like Receptor 6 43:80 Preparation of the Extracellular Domain of Recombinant Human Toll-like Receptor 6. 28161794 0 22 theme Extracellular 19:31 arg1 Domain 33:38 the Extracellular Domain 15:38 the Extracellular Domain of Recombinant Human Toll-like Receptor 6 15:80 Preparation of the Extracellular Domain of Recombinant Human Toll-like Receptor 6. 28161794 4 23 theme preparation 510:520 arg1 method 522:527 Our preparation method 506:527 Our preparation method 506:527 Our preparation method improved the level of expression of TLR6ED into a soluble fraction as compared with typical cultivation using a rotary shaker. 28161794 5 24 theme dichroism 665:673 arg1 experiments 680:690 Circular dichroism (CD) experiments 656:690 Circular dichroism (CD) experiments 656:690 Circular dichroism (CD) experiments confirmed the structural formation of TLR6ED with secondary structure contents similar to leucine-rich repeat (LRR) modules. 28161794 2 25 theme action 272:277 arg1 mechanisms 279:288 their action mechanisms 266:288 their action mechanisms 266:288 To further elucidate the function of TLRs, it is important to identify novel ligands and their action mechanisms including polymer assembly. 28161794 2 25 theme action 272:277 arg1 assembly 308:315 polymer assembly 300:315 polymer assembly 300:315 To further elucidate the function of TLRs, it is important to identify novel ligands and their action mechanisms including polymer assembly. 28161794 3 26 theme cultivation 486:496 arg1 method 498:503 the bubbling cultivation method 473:503 the bubbling cultivation method 473:503 In this study, we propose an efficient method for preparation of the extracellular domain of human Toll-like receptor 6 (TLR6ED) in Escherichia coli using the bubbling cultivation method. 28161794 5 27 theme secondary 742:750 arg1 contents 762:769 secondary structure contents 742:769 secondary structure contents similar to leucine-rich repeat (LRR) 742:806 Circular dichroism (CD) experiments confirmed the structural formation of TLR6ED with secondary structure contents similar to leucine-rich repeat (LRR) modules. 28161794 7 28 link N-linked 1225:1232 arg1 glycosylation 1234:1246 N-linked glycosylation 1225:1246 N-linked glycosylation 1225:1246 These materials would be useful for analyzing novel molecules that bind directly to TLR6, complex formations with other regulators including TLR2 and TLR4, and the functional effects of N-linked glycosylation. 28161794 5 29 theme modules 808:814 arg1 formation 717:725 the structural formation 702:725 the structural formation of TLR6ED with secondary structure contents similar to leucine-rich repeat (LRR) modules 702:814 Circular dichroism (CD) experiments confirmed the structural formation of TLR6ED with secondary structure contents similar to leucine-rich repeat (LRR) modules. 28161794 3 30 theme Toll-like 417:425 arg1 receptor 427:434 human Toll-like receptor 6 411:436 human Toll-like receptor 6 (TLR6ED) in Escherichia coli 411:465 In this study, we propose an efficient method for preparation of the extracellular domain of human Toll-like receptor 6 (TLR6ED) in Escherichia coli using the bubbling cultivation method. 28161794 3 30 theme Toll-like 417:425 arg1 TLR6ED 439:444 TLR6ED 439:444 TLR6ED 439:444 In this study, we propose an efficient method for preparation of the extracellular domain of human Toll-like receptor 6 (TLR6ED) in Escherichia coli using the bubbling cultivation method. 28161794 0 31 theme Domain 33:38 arg1 Preparation 0:10 Preparation 0:10 Preparation of the Extracellular Domain of Recombinant Human Toll-like Receptor 6 0:80 Preparation of the Extracellular Domain of Recombinant Human Toll-like Receptor 6. 28161794 6 32 theme insect 908:913 arg1 cells 915:919 Sf9 insect cells 904:919 Sf9 insect cells 904:919 In addition, we also provided a procedure for preparing this recombinant protein using Sf9 insect cells, which ensures preservation of some key posttranslational modifications often lacking in bacteria-expressed proteins. 28161794 5 33 theme structure 752:760 arg1 contents 762:769 secondary structure contents 742:769 secondary structure contents similar to leucine-rich repeat (LRR) 742:806 Circular dichroism (CD) experiments confirmed the structural formation of TLR6ED with secondary structure contents similar to leucine-rich repeat (LRR) modules. 28161794 2 34 theme TLRs 214:217 arg1 function 202:209 the function 198:209 the function of TLRs 198:217 To further elucidate the function of TLRs, it is important to identify novel ligands and their action mechanisms including polymer assembly. 28161794 3 35 theme receptor 427:434 arg1 receptor 427:434 human Toll-like receptor 6 411:436 human Toll-like receptor 6 (TLR6ED) in Escherichia coli 411:465 In this study, we propose an efficient method for preparation of the extracellular domain of human Toll-like receptor 6 (TLR6ED) in Escherichia coli using the bubbling cultivation method. 28161794 3 35 theme receptor 427:434 arg1 domain 401:406 the extracellular domain 383:406 the extracellular domain of human Toll-like receptor 6 (TLR6ED) in Escherichia coli 383:465 In this study, we propose an efficient method for preparation of the extracellular domain of human Toll-like receptor 6 (TLR6ED) in Escherichia coli using the bubbling cultivation method. 28161794 0 36 theme Human 55:59 arg1 Receptor 71:78 Recombinant Human Toll-like Receptor 6 43:80 Recombinant Human Toll-like Receptor 6 43:80 Preparation of the Extracellular Domain of Recombinant Human Toll-like Receptor 6. 28161794 6 37 theme Sf9 904:906 arg1 cells 915:919 Sf9 insect cells 904:919 Sf9 insect cells 904:919 In addition, we also provided a procedure for preparing this recombinant protein using Sf9 insect cells, which ensures preservation of some key posttranslational modifications often lacking in bacteria-expressed proteins. 28161794 5 38 theme similar 771:777 arg1 contents 762:769 secondary structure contents 742:769 secondary structure contents similar to leucine-rich repeat (LRR) 742:806 Circular dichroism (CD) experiments confirmed the structural formation of TLR6ED with secondary structure contents similar to leucine-rich repeat (LRR) modules. 28161794 7 39 theme functional 1203:1212 arg1 effects 1214:1220 the functional effects 1199:1220 the functional effects of N-linked glycosylation 1199:1246 These materials would be useful for analyzing novel molecules that bind directly to TLR6, complex formations with other regulators including TLR2 and TLR4, and the functional effects of N-linked glycosylation. 28161794 3 40 from receptor 427:434 arg1 coli 462:465 Escherichia coli 450:465 Escherichia coli 450:465 In this study, we propose an efficient method for preparation of the extracellular domain of human Toll-like receptor 6 (TLR6ED) in Escherichia coli using the bubbling cultivation method. 28161794 0 41 theme Recombinant 43:53 arg1 Receptor 71:78 Recombinant Human Toll-like Receptor 6 43:80 Recombinant Human Toll-like Receptor 6 43:80 Preparation of the Extracellular Domain of Recombinant Human Toll-like Receptor 6. 28161794 7 42 theme glycosylation 1234:1246 arg1 effects 1214:1220 the functional effects 1199:1220 the functional effects of N-linked glycosylation 1199:1246 These materials would be useful for analyzing novel molecules that bind directly to TLR6, complex formations with other regulators including TLR2 and TLR4, and the functional effects of N-linked glycosylation. 28161794 7 42 theme glycosylation 1234:1246 arg1 TLR6 1123:1126 TLR6 1123:1126 TLR6 1123:1126 These materials would be useful for analyzing novel molecules that bind directly to TLR6, complex formations with other regulators including TLR2 and TLR4, and the functional effects of N-linked glycosylation. 28161794 7 42 theme glycosylation 1234:1246 arg1 formations 1137:1146 complex formations 1129:1146 complex formations with other regulators including TLR2 and TLR4 1129:1192 These materials would be useful for analyzing novel molecules that bind directly to TLR6, complex formations with other regulators including TLR2 and TLR4, and the functional effects of N-linked glycosylation. 28161794 5 43 with TLR6ED 730:735 arg1 contents 762:769 secondary structure contents 742:769 secondary structure contents similar to leucine-rich repeat (LRR) 742:806 Circular dichroism (CD) experiments confirmed the structural formation of TLR6ED with secondary structure contents similar to leucine-rich repeat (LRR) modules. 28161794 4 44 theme rotary 641:646 arg1 shaker 648:653 a rotary shaker 639:653 a rotary shaker 639:653 Our preparation method improved the level of expression of TLR6ED into a soluble fraction as compared with typical cultivation using a rotary shaker. 28161794 1 45 theme immune 118:123 arg1 responses 125:133 immune responses 118:133 immune responses 118:133 Toll-like receptors (TLRs) mediate immune responses upon recognition of a variety of ligands. 28161794 5 46 theme Circular 656:663 arg1 CD 676:677 CD 676:677 CD 676:677 Circular dichroism (CD) experiments confirmed the structural formation of TLR6ED with secondary structure contents similar to leucine-rich repeat (LRR) modules. 28161794 5 46 theme Circular 656:663 arg1 dichroism 665:673 Circular dichroism 656:673 Circular dichroism (CD) experiments 656:690 Circular dichroism (CD) experiments confirmed the structural formation of TLR6ED with secondary structure contents similar to leucine-rich repeat (LRR) modules. 28161794 2 47 theme polymer 300:306 arg1 assembly 308:315 polymer assembly 300:315 polymer assembly 300:315 To further elucidate the function of TLRs, it is important to identify novel ligands and their action mechanisms including polymer assembly. 28161794 4 48 theme TLR6ED 565:570 arg1 expression 551:560 expression 551:560 expression of TLR6ED into a soluble fraction 551:594 Our preparation method improved the level of expression of TLR6ED into a soluble fraction as compared with typical cultivation using a rotary shaker. 28161794 0 49 theme Receptor 71:78 arg1 Receptor 71:78 Recombinant Human Toll-like Receptor 6 43:80 Recombinant Human Toll-like Receptor 6 43:80 Preparation of the Extracellular Domain of Recombinant Human Toll-like Receptor 6. 28161794 0 49 theme Receptor 71:78 arg1 Domain 33:38 the Extracellular Domain 15:38 the Extracellular Domain of Recombinant Human Toll-like Receptor 6 15:80 Preparation of the Extracellular Domain of Recombinant Human Toll-like Receptor 6. 28161794 3 50 from domain 401:406 arg1 coli 462:465 Escherichia coli 450:465 Escherichia coli 450:465 In this study, we propose an efficient method for preparation of the extracellular domain of human Toll-like receptor 6 (TLR6ED) in Escherichia coli using the bubbling cultivation method. 28161794 7 51 theme N-linked 1225:1232 arg1 glycosylation 1234:1246 N-linked glycosylation 1225:1246 N-linked glycosylation 1225:1246 These materials would be useful for analyzing novel molecules that bind directly to TLR6, complex formations with other regulators including TLR2 and TLR4, and the functional effects of N-linked glycosylation. 28161794 4 52 theme typical 613:619 arg1 cultivation 621:631 typical cultivation 613:631 typical cultivation using a rotary shaker 613:653 Our preparation method improved the level of expression of TLR6ED into a soluble fraction as compared with typical cultivation using a rotary shaker. 28161794 4 53 theme soluble 579:585 arg1 fraction 587:594 a soluble fraction 577:594 a soluble fraction 577:594 Our preparation method improved the level of expression of TLR6ED into a soluble fraction as compared with typical cultivation using a rotary shaker. 28161794 0 54 theme Toll-like 61:69 arg1 Receptor 71:78 Recombinant Human Toll-like Receptor 6 43:80 Recombinant Human Toll-like Receptor 6 43:80 Preparation of the Extracellular Domain of Recombinant Human Toll-like Receptor 6. 28161794 6 55 theme recombinant 878:888 arg1 protein 890:896 this recombinant protein 873:896 this recombinant protein 873:896 In addition, we also provided a procedure for preparing this recombinant protein using Sf9 insect cells, which ensures preservation of some key posttranslational modifications often lacking in bacteria-expressed proteins. 28161794 3 56 theme bubbling 477:484 arg1 method 498:503 the bubbling cultivation method 473:503 the bubbling cultivation method 473:503 In this study, we propose an efficient method for preparation of the extracellular domain of human Toll-like receptor 6 (TLR6ED) in Escherichia coli using the bubbling cultivation method. 28161794 6 57 theme posttranslational 961:977 arg1 modifications 979:991 some key posttranslational modifications 952:991 some key posttranslational modifications often lacking in bacteria-expressed proteins 952:1036 In addition, we also provided a procedure for preparing this recombinant protein using Sf9 insect cells, which ensures preservation of some key posttranslational modifications often lacking in bacteria-expressed proteins. 27693289 8 0 theme host 1293:1296 arg1 mechanisms 1308:1317 the host and viral mechanisms 1289:1317 mechanisms 1308:1317 Studies of the shifts in PI viral swarms will contribute to our understanding of the host and viral mechanisms that function in the maintenance of pestivirus persistent infections. 27693289 8 1 theme shifts 1223:1228 arg1 Studies 1208:1214 Studies 1208:1214 Studies of the shifts in PI viral swarms 1208:1247 Studies of the shifts in PI viral swarms will contribute to our understanding of the host and viral mechanisms that function in the maintenance of pestivirus persistent infections. 27693289 2 2 theme viruses 364:370 arg1 swarms 343:348 swarms 343:348 swarms of individual viruses 343:370 Pestivirus strains exist as quasispecies (swarms of individual viruses) in infected animals and the viral populations making up the quasispecies differ widely in size and diversity in each animal. 27693289 1 3 theme due 256:258 arg1 producers 246:254 cattle producers 239:254 cattle producers due to both acute and persistent infections 239:298 'HoBi'-like virus is an atypical group within the Pestivirus genus that is implicated in economic losses for cattle producers due to both acute and persistent infections. 27693289 0 4 from dynamics 9:16 arg1 calves 82:87 persistently infected calves 60:87 persistently infected calves 60:87 Temporal dynamics of 'HoBi'-like pestivirus quasispecies in persistently infected calves generated under experimental conditions. 27693289 2 5 theme individual 353:362 arg1 viruses 364:370 individual viruses 353:370 individual viruses 353:370 Pestivirus strains exist as quasispecies (swarms of individual viruses) in infected animals and the viral populations making up the quasispecies differ widely in size and diversity in each animal. 27693289 3 6 from quasispecies 529:540 arg1 calves 584:589 persistently infected (PI) calves 557:589 persistently infected (PI) calves 557:589 In the present study the viral quasispecies circulating in persistently infected (PI) calves, generated and maintained under experimental conditions using two different 'HoBi'-like strains, was observed over time. 27693289 3 6 from quasispecies 529:540 arg1 PI 580:581 PI 580:581 PI 580:581 In the present study the viral quasispecies circulating in persistently infected (PI) calves, generated and maintained under experimental conditions using two different 'HoBi'-like strains, was observed over time. 27693289 0 7 theme experimental 105:116 arg1 conditions 118:127 experimental conditions 105:127 experimental conditions 105:127 Temporal dynamics of 'HoBi'-like pestivirus quasispecies in persistently infected calves generated under experimental conditions. 27693289 5 8 gly glycosylation 872:884 arg2 site 886:889 a putative N-linked glycosylation site 852:889 a putative N-linked glycosylation site 852:889 Mutations observed included the loss of a putative N-linked glycosylation site in the E2 region and the change of specific residues in E1/E2. 27693289 2 9 from quasispecies 329:340 arg1 animals 385:391 infected animals 376:391 infected animals 376:391 Pestivirus strains exist as quasispecies (swarms of individual viruses) in infected animals and the viral populations making up the quasispecies differ widely in size and diversity in each animal. 27693289 8 10 theme mechanisms 1308:1317 arg1 understanding 1272:1284 our understanding 1268:1284 our understanding of the host and viral mechanisms that function in the maintenance of pestivirus persistent infections 1268:1386 Studies of the shifts in PI viral swarms will contribute to our understanding of the host and viral mechanisms that function in the maintenance of pestivirus persistent infections. 27693289 3 11 located observed 692:699 arg2 quasispecies 529:540 the viral quasispecies 519:540 the viral quasispecies 519:540 In the present study the viral quasispecies circulating in persistently infected (PI) calves, generated and maintained under experimental conditions using two different 'HoBi'-like strains, was observed over time. 27693289 3 11 located observed 692:699 arg1 study 513:517 the present study 501:517 the present study 501:517 In the present study the viral quasispecies circulating in persistently infected (PI) calves, generated and maintained under experimental conditions using two different 'HoBi'-like strains, was observed over time. 27693289 8 12 from Studies 1208:1214 arg1 swarms 1242:1247 PI viral swarms 1233:1247 PI viral swarms 1233:1247 Studies of the shifts in PI viral swarms will contribute to our understanding of the host and viral mechanisms that function in the maintenance of pestivirus persistent infections. 27693289 7 13 theme first 1084:1088 arg1 This 1072:1075 This 1072:1075 This 1072:1075 This is the first study characterizing variation in the viral swarms of animals persistently infected with HoBi-like viruses over time. 27693289 7 13 theme first 1084:1088 arg1 study 1090:1094 the first study 1080:1094 the first study characterizing variation in the viral swarms of animals persistently infected with HoBi-like viruses over time 1080:1205 This is the first study characterizing variation in the viral swarms of animals persistently infected with HoBi-like viruses over time. 27693289 4 14 from development 755:765 arg1 variability 735:745 genetic variability 727:745 genetic variability 727:745 An increase in genetic variability and the development of certain mutations was observed over time. 27693289 8 15 theme viral 1302:1306 arg1 mechanisms 1308:1317 the host and viral mechanisms 1289:1317 mechanisms 1308:1317 Studies of the shifts in PI viral swarms will contribute to our understanding of the host and viral mechanisms that function in the maintenance of pestivirus persistent infections. 27693289 1 16 theme acute 268:272 arg1 infections 289:298 both acute and persistent infections 263:298 both acute and persistent infections 263:298 'HoBi'-like virus is an atypical group within the Pestivirus genus that is implicated in economic losses for cattle producers due to both acute and persistent infections. 27693289 5 17 link N-linked 863:870 arg1 site 886:889 a putative N-linked glycosylation site 852:889 a putative N-linked glycosylation site 852:889 Mutations observed included the loss of a putative N-linked glycosylation site in the E2 region and the change of specific residues in E1/E2. 27693289 4 18 theme genetic 727:733 arg1 variability 735:745 genetic variability 727:745 genetic variability 727:745 An increase in genetic variability and the development of certain mutations was observed over time. 27693289 4 19 theme certain 770:776 arg1 mutations 778:786 certain mutations 770:786 certain mutations 770:786 An increase in genetic variability and the development of certain mutations was observed over time. 27693289 6 20 theme pestivirus 1040:1049 arg1 adaption 1024:1031 continued adaption 1014:1031 continued adaption of the pestivirus to individual hosts 1014:1069 It is hypothesized that these changes may be the results on continued adaption of the pestivirus to individual hosts. 27693289 6 21 theme individual 1054:1063 arg1 hosts 1065:1069 individual hosts 1054:1069 individual hosts 1054:1069 It is hypothesized that these changes may be the results on continued adaption of the pestivirus to individual hosts. 27693289 5 22 theme E2 898:899 arg1 region 901:906 the E2 region 894:906 the E2 region 894:906 Mutations observed included the loss of a putative N-linked glycosylation site in the E2 region and the change of specific residues in E1/E2. 27693289 3 23 theme viral 523:527 arg1 quasispecies 529:540 the viral quasispecies 519:540 the viral quasispecies 519:540 In the present study the viral quasispecies circulating in persistently infected (PI) calves, generated and maintained under experimental conditions using two different 'HoBi'-like strains, was observed over time. 27693289 1 24 theme Pestivirus 180:189 arg1 genus 191:195 the Pestivirus genus 176:195 the Pestivirus genus that is implicated in economic losses for cattle producers due to both acute and persistent infections 176:298 'HoBi'-like virus is an atypical group within the Pestivirus genus that is implicated in economic losses for cattle producers due to both acute and persistent infections. 27693289 7 25 theme animals 1144:1150 arg1 animals 1144:1150 animals 1144:1150 animals persistently infected with HoBi-like viruses over time 1144:1205 This is the first study characterizing variation in the viral swarms of animals persistently infected with HoBi-like viruses over time. 27693289 7 25 theme animals 1144:1150 arg1 swarms 1134:1139 the viral swarms 1124:1139 the viral swarms of animals persistently infected with HoBi-like viruses over time 1124:1205 This is the first study characterizing variation in the viral swarms of animals persistently infected with HoBi-like viruses over time. 27693289 5 26 from change 916:921 arg1 region 901:906 the E2 region 894:906 the E2 region 894:906 Mutations observed included the loss of a putative N-linked glycosylation site in the E2 region and the change of specific residues in E1/E2. 27693289 5 26 from change 916:921 arg1 E1/E2 947:951 E1/E2 947:951 E1/E2 947:951 Mutations observed included the loss of a putative N-linked glycosylation site in the E2 region and the change of specific residues in E1/E2. 27693289 3 27 theme infected 570:577 arg1 calves 584:589 persistently infected (PI) calves 557:589 persistently infected (PI) calves 557:589 In the present study the viral quasispecies circulating in persistently infected (PI) calves, generated and maintained under experimental conditions using two different 'HoBi'-like strains, was observed over time. 27693289 3 27 theme infected 570:577 arg1 PI 580:581 PI 580:581 PI 580:581 In the present study the viral quasispecies circulating in persistently infected (PI) calves, generated and maintained under experimental conditions using two different 'HoBi'-like strains, was observed over time. 27693289 5 28 theme N-linked 863:870 arg1 site 886:889 a putative N-linked glycosylation site 852:889 a putative N-linked glycosylation site 852:889 Mutations observed included the loss of a putative N-linked glycosylation site in the E2 region and the change of specific residues in E1/E2. 27693289 0 29 theme Temporal 0:7 arg1 dynamics 9:16 Temporal dynamics 0:16 Temporal dynamics of 'HoBi'-like pestivirus quasispecies in persistently infected calves 0:87 Temporal dynamics of 'HoBi'-like pestivirus quasispecies in persistently infected calves generated under experimental conditions. 27693289 2 30 dep quasispecies 329:340 arg1 swarms 343:348 swarms 343:348 swarms of individual viruses 343:370 Pestivirus strains exist as quasispecies (swarms of individual viruses) in infected animals and the viral populations making up the quasispecies differ widely in size and diversity in each animal. 27693289 8 31 theme PI 1233:1234 arg1 swarms 1242:1247 PI viral swarms 1233:1247 PI viral swarms 1233:1247 Studies of the shifts in PI viral swarms will contribute to our understanding of the host and viral mechanisms that function in the maintenance of pestivirus persistent infections. 27693289 2 32 theme infected 376:383 arg1 animals 385:391 infected animals 376:391 infected animals 376:391 Pestivirus strains exist as quasispecies (swarms of individual viruses) in infected animals and the viral populations making up the quasispecies differ widely in size and diversity in each animal. 27693289 1 33 theme persistent 278:287 arg1 infections 289:298 both acute and persistent infections 263:298 both acute and persistent infections 263:298 'HoBi'-like virus is an atypical group within the Pestivirus genus that is implicated in economic losses for cattle producers due to both acute and persistent infections. 27693289 5 34 theme residues 935:942 arg1 loss 844:847 the loss 840:847 the loss of a putative N-linked glycosylation site in the E2 region 840:906 Mutations observed included the loss of a putative N-linked glycosylation site in the E2 region and the change of specific residues in E1/E2. 27693289 5 34 theme residues 935:942 arg1 change 916:921 the change 912:921 the change of specific residues in E1/E2 912:951 Mutations observed included the loss of a putative N-linked glycosylation site in the E2 region and the change of specific residues in E1/E2. 27693289 8 35 theme viral 1236:1240 arg1 swarms 1242:1247 PI viral swarms 1233:1247 PI viral swarms 1233:1247 Studies of the shifts in PI viral swarms will contribute to our understanding of the host and viral mechanisms that function in the maintenance of pestivirus persistent infections. 27693289 5 36 theme specific 926:933 arg1 residues 935:942 specific residues 926:942 specific residues 926:942 Mutations observed included the loss of a putative N-linked glycosylation site in the E2 region and the change of specific residues in E1/E2. 27693289 2 37 theme Pestivirus 301:310 arg1 strains 312:318 Pestivirus strains 301:318 Pestivirus strains 301:318 Pestivirus strains exist as quasispecies (swarms of individual viruses) in infected animals and the viral populations making up the quasispecies differ widely in size and diversity in each animal. 27693289 5 38 theme site 886:889 arg1 loss 844:847 the loss 840:847 the loss of a putative N-linked glycosylation site in the E2 region 840:906 Mutations observed included the loss of a putative N-linked glycosylation site in the E2 region and the change of specific residues in E1/E2. 27693289 5 38 theme site 886:889 arg1 change 916:921 the change 912:921 the change of specific residues in E1/E2 912:951 Mutations observed included the loss of a putative N-linked glycosylation site in the E2 region and the change of specific residues in E1/E2. 27693289 0 39 theme pestivirus 33:42 arg1 quasispecies 44:55 'HoBi'-like pestivirus quasispecies 21:55 'HoBi'-like pestivirus quasispecies 21:55 Temporal dynamics of 'HoBi'-like pestivirus quasispecies in persistently infected calves generated under experimental conditions. 27693289 8 40 theme persistent 1366:1375 arg1 infections 1377:1386 pestivirus persistent infections 1355:1386 pestivirus persistent infections 1355:1386 Studies of the shifts in PI viral swarms will contribute to our understanding of the host and viral mechanisms that function in the maintenance of pestivirus persistent infections. 27693289 5 41 theme glycosylation 872:884 arg1 site 886:889 a putative N-linked glycosylation site 852:889 a putative N-linked glycosylation site 852:889 Mutations observed included the loss of a putative N-linked glycosylation site in the E2 region and the change of specific residues in E1/E2. 27693289 6 42 theme continued 1014:1022 arg1 adaption 1024:1031 continued adaption 1014:1031 continued adaption of the pestivirus to individual hosts 1014:1069 It is hypothesized that these changes may be the results on continued adaption of the pestivirus to individual hosts. 27693289 0 43 theme HoBi'-like 22:31 arg1 quasispecies 44:55 'HoBi'-like pestivirus quasispecies 21:55 'HoBi'-like pestivirus quasispecies 21:55 Temporal dynamics of 'HoBi'-like pestivirus quasispecies in persistently infected calves generated under experimental conditions. 27693289 7 44 theme viral 1128:1132 arg1 animals 1144:1150 animals 1144:1150 animals persistently infected with HoBi-like viruses over time 1144:1205 This is the first study characterizing variation in the viral swarms of animals persistently infected with HoBi-like viruses over time. 27693289 7 44 theme viral 1128:1132 arg1 swarms 1134:1139 the viral swarms 1124:1139 the viral swarms of animals persistently infected with HoBi-like viruses over time 1124:1205 This is the first study characterizing variation in the viral swarms of animals persistently infected with HoBi-like viruses over time. 27693289 3 45 theme experimental 623:634 arg1 conditions 636:645 experimental conditions 623:645 experimental conditions using two different 'HoBi'-like strains 623:685 In the present study the viral quasispecies circulating in persistently infected (PI) calves, generated and maintained under experimental conditions using two different 'HoBi'-like strains, was observed over time. 27693289 8 46 theme pestivirus 1355:1364 arg1 infections 1377:1386 pestivirus persistent infections 1355:1386 pestivirus persistent infections 1355:1386 Studies of the shifts in PI viral swarms will contribute to our understanding of the host and viral mechanisms that function in the maintenance of pestivirus persistent infections. 27693289 5 47 from loss 844:847 arg1 region 901:906 the E2 region 894:906 the E2 region 894:906 Mutations observed included the loss of a putative N-linked glycosylation site in the E2 region and the change of specific residues in E1/E2. 27693289 5 47 from loss 844:847 arg1 E1/E2 947:951 E1/E2 947:951 E1/E2 947:951 Mutations observed included the loss of a putative N-linked glycosylation site in the E2 region and the change of specific residues in E1/E2. 27693289 1 48 theme economic 219:226 arg1 losses 228:233 economic losses 219:233 economic losses for cattle producers due to both acute and persistent infections 219:298 'HoBi'-like virus is an atypical group within the Pestivirus genus that is implicated in economic losses for cattle producers due to both acute and persistent infections. 27693289 7 49 theme HoBi-like 1179:1187 arg1 viruses 1189:1195 HoBi-like viruses 1179:1195 HoBi-like viruses 1179:1195 This is the first study characterizing variation in the viral swarms of animals persistently infected with HoBi-like viruses over time. 27693289 8 50 from shifts 1223:1228 arg1 swarms 1242:1247 PI viral swarms 1233:1247 PI viral swarms 1233:1247 Studies of the shifts in PI viral swarms will contribute to our understanding of the host and viral mechanisms that function in the maintenance of pestivirus persistent infections. 27693289 6 51 from results 1003:1009 arg1 adaption 1024:1031 continued adaption 1014:1031 continued adaption of the pestivirus to individual hosts 1014:1069 It is hypothesized that these changes may be the results on continued adaption of the pestivirus to individual hosts. 27693289 0 52 theme quasispecies 44:55 arg1 dynamics 9:16 Temporal dynamics 0:16 Temporal dynamics of 'HoBi'-like pestivirus quasispecies in persistently infected calves 0:87 Temporal dynamics of 'HoBi'-like pestivirus quasispecies in persistently infected calves generated under experimental conditions. 27693289 3 53 theme HoBi'-like 668:677 arg1 strains 679:685 two different 'HoBi'-like strains 653:685 two different 'HoBi'-like strains 653:685 In the present study the viral quasispecies circulating in persistently infected (PI) calves, generated and maintained under experimental conditions using two different 'HoBi'-like strains, was observed over time. 27693289 8 54 theme infections 1377:1386 arg1 maintenance 1340:1350 the maintenance 1336:1350 the maintenance of pestivirus persistent infections 1336:1386 Studies of the shifts in PI viral swarms will contribute to our understanding of the host and viral mechanisms that function in the maintenance of pestivirus persistent infections. 27693289 1 55 theme HoBi'-like 131:140 arg1 virus 142:146 'HoBi'-like virus 130:146 'HoBi'-like virus 130:146 'HoBi'-like virus is an atypical group within the Pestivirus genus that is implicated in economic losses for cattle producers due to both acute and persistent infections. 27693289 1 55 theme HoBi'-like 131:140 arg1 group 163:167 an atypical group 151:167 an atypical group within the Pestivirus genus that is implicated in economic losses for cattle producers due to both acute and persistent infections 151:298 'HoBi'-like virus is an atypical group within the Pestivirus genus that is implicated in economic losses for cattle producers due to both acute and persistent infections. 27693289 4 56 from increase 715:722 arg1 variability 735:745 genetic variability 727:745 genetic variability 727:745 An increase in genetic variability and the development of certain mutations was observed over time. 27693289 3 57 dep quasispecies 529:540 arg1 maintained 606:615 maintained 606:615 maintained under experimental conditions using two different 'HoBi'-like strains 606:685 In the present study the viral quasispecies circulating in persistently infected (PI) calves, generated and maintained under experimental conditions using two different 'HoBi'-like strains, was observed over time. 27693289 3 57 dep quasispecies 529:540 arg1 generated 592:600 generated 592:600 generated 592:600 In the present study the viral quasispecies circulating in persistently infected (PI) calves, generated and maintained under experimental conditions using two different 'HoBi'-like strains, was observed over time. 27693289 3 58 theme different 657:665 arg1 strains 679:685 two different 'HoBi'-like strains 653:685 two different 'HoBi'-like strains 653:685 In the present study the viral quasispecies circulating in persistently infected (PI) calves, generated and maintained under experimental conditions using two different 'HoBi'-like strains, was observed over time. 27693289 4 59 theme mutations 778:786 arg1 development 755:765 the development 751:765 the development of certain mutations 751:786 An increase in genetic variability and the development of certain mutations was observed over time. 27693289 4 59 theme mutations 778:786 arg1 increase 715:722 An increase 712:722 An increase in genetic variability 712:745 An increase in genetic variability and the development of certain mutations was observed over time. 27693289 0 60 theme infected 73:80 arg1 calves 82:87 persistently infected calves 60:87 persistently infected calves 60:87 Temporal dynamics of 'HoBi'-like pestivirus quasispecies in persistently infected calves generated under experimental conditions. 27693289 2 61 theme viral 401:405 arg1 populations 407:417 the viral populations 397:417 the viral populations making up the quasispecies 397:444 Pestivirus strains exist as quasispecies (swarms of individual viruses) in infected animals and the viral populations making up the quasispecies differ widely in size and diversity in each animal. 27693289 8 62 from swarms 1242:1247 arg1 Studies 1208:1214 Studies 1208:1214 Studies of the shifts in PI viral swarms 1208:1247 Studies of the shifts in PI viral swarms will contribute to our understanding of the host and viral mechanisms that function in the maintenance of pestivirus persistent infections. 27693289 3 63 theme present 505:511 arg1 study 513:517 the present study 501:517 the present study 501:517 In the present study the viral quasispecies circulating in persistently infected (PI) calves, generated and maintained under experimental conditions using two different 'HoBi'-like strains, was observed over time. 27693289 5 64 theme putative 854:861 arg1 site 886:889 a putative N-linked glycosylation site 852:889 a putative N-linked glycosylation site 852:889 Mutations observed included the loss of a putative N-linked glycosylation site in the E2 region and the change of specific residues in E1/E2. 27693289 1 65 theme cattle 239:244 arg1 producers 246:254 cattle producers 239:254 cattle producers due to both acute and persistent infections 239:298 'HoBi'-like virus is an atypical group within the Pestivirus genus that is implicated in economic losses for cattle producers due to both acute and persistent infections. 27693289 7 66 from variation 1111:1119 arg1 animals 1144:1150 animals 1144:1150 animals persistently infected with HoBi-like viruses over time 1144:1205 This is the first study characterizing variation in the viral swarms of animals persistently infected with HoBi-like viruses over time. 27693289 7 66 from variation 1111:1119 arg1 swarms 1134:1139 the viral swarms 1124:1139 the viral swarms of animals persistently infected with HoBi-like viruses over time 1124:1205 This is the first study characterizing variation in the viral swarms of animals persistently infected with HoBi-like viruses over time. 27693289 1 67 theme atypical 154:161 arg1 virus 142:146 'HoBi'-like virus 130:146 'HoBi'-like virus 130:146 'HoBi'-like virus is an atypical group within the Pestivirus genus that is implicated in economic losses for cattle producers due to both acute and persistent infections. 27693289 1 67 theme atypical 154:161 arg1 group 163:167 an atypical group 151:167 an atypical group within the Pestivirus genus that is implicated in economic losses for cattle producers due to both acute and persistent infections 151:298 'HoBi'-like virus is an atypical group within the Pestivirus genus that is implicated in economic losses for cattle producers due to both acute and persistent infections. 26980432 0 0 theme Subunit 79:85 arg1 Gene 93:96 Luteinizing Hormone Beta Subunit (lhb) Gene 54:96 Luteinizing Hormone Beta Subunit (lhb) Gene in Catla catla 54:111 Identification, cDNA Cloning, and Characterization of Luteinizing Hormone Beta Subunit (lhb) Gene in Catla catla. 26980432 5 1 theme glycosylation 645:657 arg1 site 659:662 a single N-linked glycosylation site 627:662 a single N-linked glycosylation site (NET) 627:668 The coding sequence of lhb gene consist of a single N-linked glycosylation site (NET) and 12 cysteine knot residues. 26980432 9 2 dep identification 1111:1124 arg1 the 1107:1109 the 1107:1109 the 1107:1109 To best our knowledge, this is the first report on the identification, molecular characterization and structural information regarding luteinizing hormone in Indian major carp. 26980432 0 3 theme Beta 74:77 arg1 Gene 93:96 Luteinizing Hormone Beta Subunit (lhb) Gene 54:96 Luteinizing Hormone Beta Subunit (lhb) Gene in Catla catla 54:111 Identification, cDNA Cloning, and Characterization of Luteinizing Hormone Beta Subunit (lhb) Gene in Catla catla. 26980432 7 4 theme 3D 844:845 arg1 protein 861:867 3D structure Lhβ protein 844:867 3D structure Lhβ protein 844:867 3D structure Lhβ protein comprises of five β-sheets and six coils/loops. 26980432 3 5 theme cDNA 374:377 arg1 sequence 379:386 cDNA sequence 374:386 cDNA sequence 374:386 The lhb full-length of cDNA sequence is 629 bp which consists of 43bp 5'-UTR (untranslated region) 447bp, ORF(open reading frame) and 139 bp of 3'-UTR respectively. 26980432 0 6 theme lhb 88:90 arg1 Gene 93:96 Luteinizing Hormone Beta Subunit (lhb) Gene 54:96 Luteinizing Hormone Beta Subunit (lhb) Gene in Catla catla 54:111 Identification, cDNA Cloning, and Characterization of Luteinizing Hormone Beta Subunit (lhb) Gene in Catla catla. 26980432 0 7 from Identification 0:13 arg1 catla 107:111 catla 107:111 catla 107:111 Identification, cDNA Cloning, and Characterization of Luteinizing Hormone Beta Subunit (lhb) Gene in Catla catla. 26980432 8 8 theme qPCR 921:924 arg1 results 926:932 The qPCR results 917:932 The qPCR results 917:932 The qPCR results revealed lhb mRNA is mainly expressed in the pituitary, ovary while moderate expression was observed in brain and testis. 26980432 7 9 theme structure 847:855 arg1 protein 861:867 3D structure Lhβ protein 844:867 3D structure Lhβ protein 844:867 3D structure Lhβ protein comprises of five β-sheets and six coils/loops. 26980432 3 10 theme open 461:464 arg1 bp 395:396 629 bp 391:396 629 bp which consists of 43bp 5'-UTR (untranslated region) 447bp 391:454 The lhb full-length of cDNA sequence is 629 bp which consists of 43bp 5'-UTR (untranslated region) 447bp, ORF(open reading frame) and 139 bp of 3'-UTR respectively. 26980432 3 10 theme open 461:464 arg1 frame 474:478 open reading frame 461:478 open reading frame 461:478 The lhb full-length of cDNA sequence is 629 bp which consists of 43bp 5'-UTR (untranslated region) 447bp, ORF(open reading frame) and 139 bp of 3'-UTR respectively. 26980432 9 11 theme structural 1158:1167 arg1 information 1169:1179 structural information 1158:1179 structural information 1158:1179 To best our knowledge, this is the first report on the identification, molecular characterization and structural information regarding luteinizing hormone in Indian major carp. 26980432 8 12 located observed 1026:1033 arg1 testis 1048:1053 testis 1048:1053 testis 1048:1053 The qPCR results revealed lhb mRNA is mainly expressed in the pituitary, ovary while moderate expression was observed in brain and testis. 26980432 8 12 located observed 1026:1033 arg1 brain 1038:1042 brain 1038:1042 brain 1038:1042 The qPCR results revealed lhb mRNA is mainly expressed in the pituitary, ovary while moderate expression was observed in brain and testis. 26980432 8 12 located observed 1026:1033 arg2 expression 1011:1020 moderate expression 1002:1020 moderate expression 1002:1020 The qPCR results revealed lhb mRNA is mainly expressed in the pituitary, ovary while moderate expression was observed in brain and testis. 26980432 6 13 theme high 774:777 arg1 similarity 779:788 high similarity 774:788 high similarity with Carassius auratus followed by Gobiocypris rarus 774:841 Phylogenetic analysis of C. catla Lhβ deduced amino acid sequence showed high similarity with Carassius auratus followed by Gobiocypris rarus. 26980432 8 14 dep observed 1026:1033 arg1 ovary 990:994 ovary 990:994 ovary 990:994 The qPCR results revealed lhb mRNA is mainly expressed in the pituitary, ovary while moderate expression was observed in brain and testis. 26980432 3 15 theme reading 466:472 arg1 bp 395:396 629 bp 391:396 629 bp which consists of 43bp 5'-UTR (untranslated region) 447bp 391:454 The lhb full-length of cDNA sequence is 629 bp which consists of 43bp 5'-UTR (untranslated region) 447bp, ORF(open reading frame) and 139 bp of 3'-UTR respectively. 26980432 3 15 theme reading 466:472 arg1 frame 474:478 open reading frame 461:478 open reading frame 461:478 The lhb full-length of cDNA sequence is 629 bp which consists of 43bp 5'-UTR (untranslated region) 447bp, ORF(open reading frame) and 139 bp of 3'-UTR respectively. 26980432 0 16 theme Gene 93:96 arg1 Identification 0:13 Identification 0:13 Identification 0:13 Identification, cDNA Cloning, and Characterization of Luteinizing Hormone Beta Subunit (lhb) Gene in Catla catla. 26980432 0 16 theme Gene 93:96 arg1 Cloning 21:27 cDNA Cloning 16:27 cDNA Cloning 16:27 Identification, cDNA Cloning, and Characterization of Luteinizing Hormone Beta Subunit (lhb) Gene in Catla catla. 26980432 0 16 theme Gene 93:96 arg1 Characterization 34:49 Characterization 34:49 Characterization 34:49 Identification, cDNA Cloning, and Characterization of Luteinizing Hormone Beta Subunit (lhb) Gene in Catla catla. 26980432 0 17 from Characterization 34:49 arg1 catla 107:111 catla 107:111 catla 107:111 Identification, cDNA Cloning, and Characterization of Luteinizing Hormone Beta Subunit (lhb) Gene in Catla catla. 26980432 8 18 theme moderate 1002:1009 arg1 expression 1011:1020 moderate expression 1002:1020 moderate expression 1002:1020 The qPCR results revealed lhb mRNA is mainly expressed in the pituitary, ovary while moderate expression was observed in brain and testis. 26980432 2 19 theme hormone 258:264 arg1 beta 266:269 luteinizing hormone beta 246:269 the present study luteinizing hormone beta 228:269 In the present study luteinizing hormone beta, (lhb) subunit gene was cloned and characterized from the brain of Catla catla. 26980432 2 20 dep study 240:244 arg1 beta 266:269 luteinizing hormone beta 246:269 the present study luteinizing hormone beta 228:269 In the present study luteinizing hormone beta, (lhb) subunit gene was cloned and characterized from the brain of Catla catla. 26980432 1 21 theme significant 143:153 arg1 role 155:158 a significant role 141:158 a significant role 141:158 Reproductive hormones play a significant role in the gonadal development and gametogenesis process of animals. 26980432 6 22 theme acid 753:756 arg1 sequence 758:765 C. catla Lhβ deduced amino acid sequence 726:765 C. catla Lhβ deduced amino acid sequence 726:765 Phylogenetic analysis of C. catla Lhβ deduced amino acid sequence showed high similarity with Carassius auratus followed by Gobiocypris rarus. 26980432 2 23 theme luteinizing 246:256 arg1 beta 266:269 luteinizing hormone beta 246:269 the present study luteinizing hormone beta 228:269 In the present study luteinizing hormone beta, (lhb) subunit gene was cloned and characterized from the brain of Catla catla. 26980432 9 24 theme first 1091:1095 arg1 report 1097:1102 the first report 1087:1102 the first report on the identification, molecular characterization and structural information regarding luteinizing hormone in Indian major carp 1087:1230 To best our knowledge, this is the first report on the identification, molecular characterization and structural information regarding luteinizing hormone in Indian major carp. 26980432 9 24 theme first 1091:1095 arg1 this 1079:1082 this 1079:1082 this 1079:1082 To best our knowledge, this is the first report on the identification, molecular characterization and structural information regarding luteinizing hormone in Indian major carp. 26980432 2 25 theme catla 344:348 arg1 brain 329:333 the brain 325:333 the brain of Catla catla 325:348 In the present study luteinizing hormone beta, (lhb) subunit gene was cloned and characterized from the brain of Catla catla. 26980432 6 26 theme amino 747:751 arg1 sequence 758:765 C. catla Lhβ deduced amino acid sequence 726:765 C. catla Lhβ deduced amino acid sequence 726:765 Phylogenetic analysis of C. catla Lhβ deduced amino acid sequence showed high similarity with Carassius auratus followed by Gobiocypris rarus. 26980432 5 27 theme single 629:634 arg1 site 659:662 a single N-linked glycosylation site 627:662 a single N-linked glycosylation site (NET) 627:668 The coding sequence of lhb gene consist of a single N-linked glycosylation site (NET) and 12 cysteine knot residues. 26980432 2 28 theme subunit 278:284 arg1 gene 286:289 (lhb) subunit gene 272:289 (lhb) subunit gene 272:289 In the present study luteinizing hormone beta, (lhb) subunit gene was cloned and characterized from the brain of Catla catla. 26980432 6 29 theme sequence 758:765 arg1 analysis 714:721 Phylogenetic analysis 701:721 Phylogenetic analysis of C. catla Lhβ deduced amino acid sequence 701:765 Phylogenetic analysis of C. catla Lhβ deduced amino acid sequence showed high similarity with Carassius auratus followed by Gobiocypris rarus. 26980432 2 30 theme Catla 338:342 arg1 catla 344:348 Catla catla 338:348 Catla catla 338:348 In the present study luteinizing hormone beta, (lhb) subunit gene was cloned and characterized from the brain of Catla catla. 26980432 5 31 theme cysteine 677:684 arg1 residues 691:698 12 cysteine knot residues 674:698 12 cysteine knot residues 674:698 The coding sequence of lhb gene consist of a single N-linked glycosylation site (NET) and 12 cysteine knot residues. 26980432 8 32 theme lhb 943:945 arg1 mRNA 947:950 lhb mRNA 943:950 lhb mRNA 943:950 The qPCR results revealed lhb mRNA is mainly expressed in the pituitary, ovary while moderate expression was observed in brain and testis. 26980432 9 33 theme molecular 1127:1135 arg1 characterization 1137:1152 molecular characterization 1127:1152 molecular characterization 1127:1152 To best our knowledge, this is the first report on the identification, molecular characterization and structural information regarding luteinizing hormone in Indian major carp. 26980432 3 34 theme sequence 379:386 arg1 full-length 359:369 The lhb full-length 351:369 The lhb full-length of cDNA sequence 351:386 The lhb full-length of cDNA sequence is 629 bp which consists of 43bp 5'-UTR (untranslated region) 447bp, ORF(open reading frame) and 139 bp of 3'-UTR respectively. 26980432 3 34 theme sequence 379:386 arg1 bp 395:396 629 bp 391:396 629 bp which consists of 43bp 5'-UTR (untranslated region) 447bp 391:454 The lhb full-length of cDNA sequence is 629 bp which consists of 43bp 5'-UTR (untranslated region) 447bp, ORF(open reading frame) and 139 bp of 3'-UTR respectively. 26980432 5 35 theme knot 686:689 arg1 residues 691:698 12 cysteine knot residues 674:698 12 cysteine knot residues 674:698 The coding sequence of lhb gene consist of a single N-linked glycosylation site (NET) and 12 cysteine knot residues. 26980432 9 36 theme Indian 1214:1219 arg1 carp 1227:1230 Indian major carp 1214:1230 Indian major carp 1214:1230 To best our knowledge, this is the first report on the identification, molecular characterization and structural information regarding luteinizing hormone in Indian major carp. 26980432 5 37 theme coding 588:593 arg1 sequence 595:602 The coding sequence 584:602 The coding sequence of lhb gene 584:614 The coding sequence of lhb gene consist of a single N-linked glycosylation site (NET) and 12 cysteine knot residues. 26980432 9 38 theme best 1059:1062 arg1 knowledge 1068:1076 best our knowledge 1059:1076 best our knowledge 1059:1076 To best our knowledge, this is the first report on the identification, molecular characterization and structural information regarding luteinizing hormone in Indian major carp. 26980432 2 39 theme lhb 273:275 arg1 gene 286:289 (lhb) subunit gene 272:289 (lhb) subunit gene 272:289 In the present study luteinizing hormone beta, (lhb) subunit gene was cloned and characterized from the brain of Catla catla. 26980432 1 40 theme gonadal 167:173 arg1 development 175:185 gonadal development 167:185 gonadal development 167:185 Reproductive hormones play a significant role in the gonadal development and gametogenesis process of animals. 26980432 0 41 theme cDNA 16:19 arg1 Cloning 21:27 cDNA Cloning 16:27 cDNA Cloning 16:27 Identification, cDNA Cloning, and Characterization of Luteinizing Hormone Beta Subunit (lhb) Gene in Catla catla. 26980432 9 42 theme major 1221:1225 arg1 carp 1227:1230 Indian major carp 1214:1230 Indian major carp 1214:1230 To best our knowledge, this is the first report on the identification, molecular characterization and structural information regarding luteinizing hormone in Indian major carp. 26980432 5 43 dep site 659:662 arg1 NET 665:667 NET 665:667 NET 665:667 The coding sequence of lhb gene consist of a single N-linked glycosylation site (NET) and 12 cysteine knot residues. 26980432 6 44 theme deduced 739:745 arg1 sequence 758:765 C. catla Lhβ deduced amino acid sequence 726:765 C. catla Lhβ deduced amino acid sequence 726:765 Phylogenetic analysis of C. catla Lhβ deduced amino acid sequence showed high similarity with Carassius auratus followed by Gobiocypris rarus. 26980432 5 45 link N-linked 636:643 arg1 site 659:662 a single N-linked glycosylation site 627:662 a single N-linked glycosylation site (NET) 627:668 The coding sequence of lhb gene consist of a single N-linked glycosylation site (NET) and 12 cysteine knot residues. 26980432 4 46 theme acids 577:581 arg1 peptide 556:562 a peptide 554:562 a peptide of 148 amino acids 554:581 The coding region of lhb gene encoded a peptide of 148 amino acids. 26980432 4 46 theme acids 577:581 arg1 region 527:532 The coding region 516:532 The coding region of lhb gene 516:544 The coding region of lhb gene encoded a peptide of 148 amino acids. 26980432 6 47 theme Lhβ 735:737 arg1 sequence 758:765 C. catla Lhβ deduced amino acid sequence 726:765 C. catla Lhβ deduced amino acid sequence 726:765 Phylogenetic analysis of C. catla Lhβ deduced amino acid sequence showed high similarity with Carassius auratus followed by Gobiocypris rarus. 26980432 3 48 theme 3'-UTR 495:500 arg1 frame 474:478 open reading frame 461:478 open reading frame 461:478 The lhb full-length of cDNA sequence is 629 bp which consists of 43bp 5'-UTR (untranslated region) 447bp, ORF(open reading frame) and 139 bp of 3'-UTR respectively. 26980432 3 48 theme 3'-UTR 495:500 arg1 bp 489:490 139 bp 485:490 139 bp of 3'-UTR respectively 485:513 The lhb full-length of cDNA sequence is 629 bp which consists of 43bp 5'-UTR (untranslated region) 447bp, ORF(open reading frame) and 139 bp of 3'-UTR respectively. 26980432 3 48 theme 3'-UTR 495:500 arg1 full-length 359:369 The lhb full-length 351:369 The lhb full-length of cDNA sequence 351:386 The lhb full-length of cDNA sequence is 629 bp which consists of 43bp 5'-UTR (untranslated region) 447bp, ORF(open reading frame) and 139 bp of 3'-UTR respectively. 26980432 3 48 theme 3'-UTR 495:500 arg1 ORF 457:459 ORF 457:459 ORF 457:459 The lhb full-length of cDNA sequence is 629 bp which consists of 43bp 5'-UTR (untranslated region) 447bp, ORF(open reading frame) and 139 bp of 3'-UTR respectively. 26980432 3 48 theme 3'-UTR 495:500 arg1 bp 395:396 629 bp 391:396 629 bp which consists of 43bp 5'-UTR (untranslated region) 447bp 391:454 The lhb full-length of cDNA sequence is 629 bp which consists of 43bp 5'-UTR (untranslated region) 447bp, ORF(open reading frame) and 139 bp of 3'-UTR respectively. 26980432 9 49 from hormone 1203:1209 arg1 carp 1227:1230 Indian major carp 1214:1230 Indian major carp 1214:1230 To best our knowledge, this is the first report on the identification, molecular characterization and structural information regarding luteinizing hormone in Indian major carp. 26980432 5 50 theme lhb 607:609 arg1 gene 611:614 lhb gene 607:614 lhb gene 607:614 The coding sequence of lhb gene consist of a single N-linked glycosylation site (NET) and 12 cysteine knot residues. 26980432 6 51 dep Gobiocypris 825:835 arg1 rarus 837:841 Gobiocypris rarus 825:841 Gobiocypris rarus 825:841 Phylogenetic analysis of C. catla Lhβ deduced amino acid sequence showed high similarity with Carassius auratus followed by Gobiocypris rarus. 26980432 4 52 theme gene 541:544 arg1 peptide 556:562 a peptide 554:562 a peptide of 148 amino acids 554:581 The coding region of lhb gene encoded a peptide of 148 amino acids. 26980432 4 52 theme gene 541:544 arg1 region 527:532 The coding region 516:532 The coding region of lhb gene 516:544 The coding region of lhb gene encoded a peptide of 148 amino acids. 26980432 5 53 theme gene 611:614 arg1 sequence 595:602 The coding sequence 584:602 The coding sequence of lhb gene 584:614 The coding sequence of lhb gene consist of a single N-linked glycosylation site (NET) and 12 cysteine knot residues. 26980432 5 54 theme N-linked 636:643 arg1 site 659:662 a single N-linked glycosylation site 627:662 a single N-linked glycosylation site (NET) 627:668 The coding sequence of lhb gene consist of a single N-linked glycosylation site (NET) and 12 cysteine knot residues. 26980432 9 55 theme luteinizing 1191:1201 arg1 hormone 1203:1209 luteinizing hormone 1191:1209 luteinizing hormone in Indian major carp 1191:1230 To best our knowledge, this is the first report on the identification, molecular characterization and structural information regarding luteinizing hormone in Indian major carp. 26980432 6 56 with similarity 779:788 arg1 auratus 805:811 Carassius auratus 795:811 Carassius auratus followed by Gobiocypris rarus 795:841 Phylogenetic analysis of C. catla Lhβ deduced amino acid sequence showed high similarity with Carassius auratus followed by Gobiocypris rarus. 26980432 3 57 theme lhb 355:357 arg1 full-length 359:369 The lhb full-length 351:369 The lhb full-length of cDNA sequence 351:386 The lhb full-length of cDNA sequence is 629 bp which consists of 43bp 5'-UTR (untranslated region) 447bp, ORF(open reading frame) and 139 bp of 3'-UTR respectively. 26980432 3 57 theme lhb 355:357 arg1 bp 395:396 629 bp 391:396 629 bp which consists of 43bp 5'-UTR (untranslated region) 447bp 391:454 The lhb full-length of cDNA sequence is 629 bp which consists of 43bp 5'-UTR (untranslated region) 447bp, ORF(open reading frame) and 139 bp of 3'-UTR respectively. 26980432 6 58 theme Carassius 795:803 arg1 auratus 805:811 Carassius auratus 795:811 Carassius auratus followed by Gobiocypris rarus 795:841 Phylogenetic analysis of C. catla Lhβ deduced amino acid sequence showed high similarity with Carassius auratus followed by Gobiocypris rarus. 26980432 0 59 from Gene 93:96 arg1 catla 107:111 catla 107:111 catla 107:111 Identification, cDNA Cloning, and Characterization of Luteinizing Hormone Beta Subunit (lhb) Gene in Catla catla. 26980432 3 60 theme untranslated 429:440 arg1 5'-UTR 421:426 5'-UTR 421:426 43bp 5'-UTR (untranslated region) 447bp 416:454 The lhb full-length of cDNA sequence is 629 bp which consists of 43bp 5'-UTR (untranslated region) 447bp, ORF(open reading frame) and 139 bp of 3'-UTR respectively. 26980432 3 60 theme untranslated 429:440 arg1 region 442:447 untranslated region 429:447 untranslated region 429:447 The lhb full-length of cDNA sequence is 629 bp which consists of 43bp 5'-UTR (untranslated region) 447bp, ORF(open reading frame) and 139 bp of 3'-UTR respectively. 26980432 9 61 from report 1097:1102 arg1 identification 1111:1124 identification 1111:1124 identification 1111:1124 To best our knowledge, this is the first report on the identification, molecular characterization and structural information regarding luteinizing hormone in Indian major carp. 26980432 9 61 from report 1097:1102 arg1 characterization 1137:1152 molecular characterization 1127:1152 molecular characterization 1127:1152 To best our knowledge, this is the first report on the identification, molecular characterization and structural information regarding luteinizing hormone in Indian major carp. 26980432 9 61 from report 1097:1102 arg1 information 1169:1179 structural information 1158:1179 structural information 1158:1179 To best our knowledge, this is the first report on the identification, molecular characterization and structural information regarding luteinizing hormone in Indian major carp. 26980432 3 62 theme 43bp 416:419 arg1 447bp 450:454 43bp 5'-UTR (untranslated region) 447bp 416:454 43bp 5'-UTR (untranslated region) 447bp 416:454 The lhb full-length of cDNA sequence is 629 bp which consists of 43bp 5'-UTR (untranslated region) 447bp, ORF(open reading frame) and 139 bp of 3'-UTR respectively. 26980432 5 63 gly glycosylation 645:657 arg2 site 659:662 a single N-linked glycosylation site 627:662 a single N-linked glycosylation site (NET) 627:668 The coding sequence of lhb gene consist of a single N-linked glycosylation site (NET) and 12 cysteine knot residues. 26980432 6 64 theme Phylogenetic 701:712 arg1 analysis 714:721 Phylogenetic analysis 701:721 Phylogenetic analysis of C. catla Lhβ deduced amino acid sequence 701:765 Phylogenetic analysis of C. catla Lhβ deduced amino acid sequence showed high similarity with Carassius auratus followed by Gobiocypris rarus. 26980432 2 65 theme present 232:238 arg1 study 240:244 the present study luteinizing hormone beta 228:269 the present study luteinizing hormone beta 228:269 In the present study luteinizing hormone beta, (lhb) subunit gene was cloned and characterized from the brain of Catla catla. 26980432 3 66 theme 5'-UTR 421:426 arg1 447bp 450:454 43bp 5'-UTR (untranslated region) 447bp 416:454 43bp 5'-UTR (untranslated region) 447bp 416:454 The lhb full-length of cDNA sequence is 629 bp which consists of 43bp 5'-UTR (untranslated region) 447bp, ORF(open reading frame) and 139 bp of 3'-UTR respectively. 26980432 0 67 from catla 107:111 arg1 Identification 0:13 Identification 0:13 Identification 0:13 Identification, cDNA Cloning, and Characterization of Luteinizing Hormone Beta Subunit (lhb) Gene in Catla catla. 26980432 0 67 from catla 107:111 arg1 Cloning 21:27 cDNA Cloning 16:27 cDNA Cloning 16:27 Identification, cDNA Cloning, and Characterization of Luteinizing Hormone Beta Subunit (lhb) Gene in Catla catla. 26980432 0 67 from catla 107:111 arg1 Characterization 34:49 Characterization 34:49 Characterization 34:49 Identification, cDNA Cloning, and Characterization of Luteinizing Hormone Beta Subunit (lhb) Gene in Catla catla. 26980432 0 68 theme Hormone 66:72 arg1 Gene 93:96 Luteinizing Hormone Beta Subunit (lhb) Gene 54:96 Luteinizing Hormone Beta Subunit (lhb) Gene in Catla catla 54:111 Identification, cDNA Cloning, and Characterization of Luteinizing Hormone Beta Subunit (lhb) Gene in Catla catla. 26980432 4 69 theme lhb 537:539 arg1 gene 541:544 lhb gene 537:544 lhb gene 537:544 The coding region of lhb gene encoded a peptide of 148 amino acids. 26980432 1 70 theme Reproductive 114:125 arg1 hormones 127:134 Reproductive hormones 114:134 Reproductive hormones 114:134 Reproductive hormones play a significant role in the gonadal development and gametogenesis process of animals. 26980432 1 71 theme animals 216:222 arg1 development 175:185 gonadal development 167:185 gonadal development 167:185 Reproductive hormones play a significant role in the gonadal development and gametogenesis process of animals. 26980432 1 71 theme animals 216:222 arg1 gametogenesis 191:203 gametogenesis 191:203 gametogenesis 191:203 Reproductive hormones play a significant role in the gonadal development and gametogenesis process of animals. 26980432 0 72 theme Luteinizing 54:64 arg1 Gene 93:96 Luteinizing Hormone Beta Subunit (lhb) Gene 54:96 Luteinizing Hormone Beta Subunit (lhb) Gene in Catla catla 54:111 Identification, cDNA Cloning, and Characterization of Luteinizing Hormone Beta Subunit (lhb) Gene in Catla catla. 26980432 0 73 from Cloning 21:27 arg1 catla 107:111 catla 107:111 catla 107:111 Identification, cDNA Cloning, and Characterization of Luteinizing Hormone Beta Subunit (lhb) Gene in Catla catla. 26980432 1 74 dep development 175:185 arg1 process 205:211 process 205:211 process 205:211 Reproductive hormones play a significant role in the gonadal development and gametogenesis process of animals. 26980432 1 74 dep development 175:185 arg1 the 163:165 the 163:165 the 163:165 Reproductive hormones play a significant role in the gonadal development and gametogenesis process of animals. 26980432 7 75 theme Lhβ 857:859 arg1 protein 861:867 3D structure Lhβ protein 844:867 3D structure Lhβ protein 844:867 3D structure Lhβ protein comprises of five β-sheets and six coils/loops. 26980432 4 76 theme amino 571:575 arg1 acids 577:581 148 amino acids 567:581 148 amino acids 567:581 The coding region of lhb gene encoded a peptide of 148 amino acids. 26980432 4 77 theme coding 520:525 arg1 peptide 556:562 a peptide 554:562 a peptide of 148 amino acids 554:581 The coding region of lhb gene encoded a peptide of 148 amino acids. 26980432 4 77 theme coding 520:525 arg1 region 527:532 The coding region 516:532 The coding region of lhb gene 516:544 The coding region of lhb gene encoded a peptide of 148 amino acids. 26452918 0 0 theme chromatography-electrospray 94:120 arg1 spectrometry 127:138 liquid chromatography-electrospray mass spectrometry 87:138 liquid chromatography-electrospray mass spectrometry 87:138 Hydrazino-s-triazine based labelling reagents for highly sensitive glycan analysis via liquid chromatography-electrospray mass spectrometry. 26452918 5 1 theme labelling 917:925 arg1 example 951:957 an example 948:957 an example for highly sensitive profiling of N-linked glycans 948:1008 Furthermore, the most optimal labelling reagent was taken as an example for highly sensitive profiling of N-linked glycans both cleaved from chicken avidin and glycoproteins in human serum, indicating prospective availability for these labelling reagents in frontier of glycomics researches. 26452918 5 1 theme labelling 917:925 arg1 reagent 927:933 the most optimal labelling reagent 900:933 the most optimal labelling reagent 900:933 Furthermore, the most optimal labelling reagent was taken as an example for highly sensitive profiling of N-linked glycans both cleaved from chicken avidin and glycoproteins in human serum, indicating prospective availability for these labelling reagents in frontier of glycomics researches. 26452918 1 2 theme mass 187:190 arg1 MS 206:207 MS 206:207 MS 206:207 Labelling strategy plays an important role in mass spectrometry (MS) based glycan analysis due to the high hydrophilicity and low ionization efficiency of glycans. 26452918 1 2 theme mass 187:190 arg1 spectrometry 192:203 mass spectrometry 187:203 mass spectrometry (MS) based glycan analysis 187:230 Labelling strategy plays an important role in mass spectrometry (MS) based glycan analysis due to the high hydrophilicity and low ionization efficiency of glycans. 26452918 1 3 theme low 267:269 arg1 efficiency 282:291 low ionization efficiency 267:291 low ionization efficiency 267:291 Labelling strategy plays an important role in mass spectrometry (MS) based glycan analysis due to the high hydrophilicity and low ionization efficiency of glycans. 26452918 0 4 theme liquid 87:92 arg1 spectrometry 127:138 liquid chromatography-electrospray mass spectrometry 87:138 liquid chromatography-electrospray mass spectrometry 87:138 Hydrazino-s-triazine based labelling reagents for highly sensitive glycan analysis via liquid chromatography-electrospray mass spectrometry. 26452918 5 5 theme researches 1167:1176 arg1 frontier 1145:1152 frontier 1145:1152 frontier of glycomics researches 1145:1176 Furthermore, the most optimal labelling reagent was taken as an example for highly sensitive profiling of N-linked glycans both cleaved from chicken avidin and glycoproteins in human serum, indicating prospective availability for these labelling reagents in frontier of glycomics researches. 26452918 1 6 theme spectrometry 192:203 arg1 analysis 223:230 mass spectrometry (MS) based glycan analysis 187:230 mass spectrometry (MS) based glycan analysis 187:230 Labelling strategy plays an important role in mass spectrometry (MS) based glycan analysis due to the high hydrophilicity and low ionization efficiency of glycans. 26452918 1 7 theme ionization 271:280 arg1 efficiency 282:291 low ionization efficiency 267:291 low ionization efficiency 267:291 Labelling strategy plays an important role in mass spectrometry (MS) based glycan analysis due to the high hydrophilicity and low ionization efficiency of glycans. 26452918 2 8 theme controllable 389:400 arg1 conditions 402:411 facile and controllable conditions 378:411 facile and controllable conditions 378:411 Ten hydrazino-s-triazine based labelling reagents were synthesized under facile and controllable conditions for highly sensitive liquid chromatography-electrospray mass spectrometry glycan analysis in this work. 26452918 2 9 theme hydrazino-s-triazine 309:328 arg1 reagents 346:353 Ten hydrazino-s-triazine based labelling reagents 305:353 Ten hydrazino-s-triazine based labelling reagents 305:353 Ten hydrazino-s-triazine based labelling reagents were synthesized under facile and controllable conditions for highly sensitive liquid chromatography-electrospray mass spectrometry glycan analysis in this work. 26452918 2 10 theme based 330:334 arg1 reagents 346:353 Ten hydrazino-s-triazine based labelling reagents 305:353 Ten hydrazino-s-triazine based labelling reagents 305:353 Ten hydrazino-s-triazine based labelling reagents were synthesized under facile and controllable conditions for highly sensitive liquid chromatography-electrospray mass spectrometry glycan analysis in this work. 26452918 0 11 theme mass 122:125 arg1 spectrometry 127:138 liquid chromatography-electrospray mass spectrometry 87:138 liquid chromatography-electrospray mass spectrometry 87:138 Hydrazino-s-triazine based labelling reagents for highly sensitive glycan analysis via liquid chromatography-electrospray mass spectrometry. 26452918 3 12 theme labelling 582:590 arg1 reagents 592:599 these new labelling reagents 572:599 these new labelling reagents 572:599 Attached to N-glycans through non-reductive reactions, these new labelling reagents were evaluated in aspect of the differently enhanced glycan response to mass spectrometry. 26452918 4 13 with analysis 782:789 arg1 linearity 809:817 satisfactory linearity 796:817 satisfactory linearity 796:817 Three of the ten labelling reagents demonstrated to be reliable and remarkable for glycan analysis with satisfactory linearity and lowered limits of detection using maltoheptaose (DP7) as model. 26452918 4 14 theme labelling 709:717 arg1 reagents 719:726 the ten labelling reagents 701:726 the ten labelling reagents 701:726 Three of the ten labelling reagents demonstrated to be reliable and remarkable for glycan analysis with satisfactory linearity and lowered limits of detection using maltoheptaose (DP7) as model. 26452918 5 15 theme human 1064:1068 arg1 serum 1070:1074 human serum 1064:1074 human serum 1064:1074 Furthermore, the most optimal labelling reagent was taken as an example for highly sensitive profiling of N-linked glycans both cleaved from chicken avidin and glycoproteins in human serum, indicating prospective availability for these labelling reagents in frontier of glycomics researches. 26452918 5 16 from availability 1100:1111 arg1 frontier 1145:1152 frontier 1145:1152 frontier of glycomics researches 1145:1176 Furthermore, the most optimal labelling reagent was taken as an example for highly sensitive profiling of N-linked glycans both cleaved from chicken avidin and glycoproteins in human serum, indicating prospective availability for these labelling reagents in frontier of glycomics researches. 26452918 2 17 theme mass 469:472 arg1 spectrometry 474:485 highly sensitive liquid chromatography-electrospray mass spectrometry 417:485 highly sensitive liquid chromatography-electrospray mass spectrometry glycan analysis 417:501 Ten hydrazino-s-triazine based labelling reagents were synthesized under facile and controllable conditions for highly sensitive liquid chromatography-electrospray mass spectrometry glycan analysis in this work. 26452918 2 18 theme chromatography-electrospray 441:467 arg1 spectrometry 474:485 highly sensitive liquid chromatography-electrospray mass spectrometry 417:485 highly sensitive liquid chromatography-electrospray mass spectrometry glycan analysis 417:501 Ten hydrazino-s-triazine based labelling reagents were synthesized under facile and controllable conditions for highly sensitive liquid chromatography-electrospray mass spectrometry glycan analysis in this work. 26452918 3 19 theme glycan 654:659 arg1 response 661:668 the differently enhanced glycan response 629:668 the differently enhanced glycan response to mass spectrometry 629:689 Attached to N-glycans through non-reductive reactions, these new labelling reagents were evaluated in aspect of the differently enhanced glycan response to mass spectrometry. 26452918 2 20 theme liquid 434:439 arg1 spectrometry 474:485 highly sensitive liquid chromatography-electrospray mass spectrometry 417:485 highly sensitive liquid chromatography-electrospray mass spectrometry glycan analysis 417:501 Ten hydrazino-s-triazine based labelling reagents were synthesized under facile and controllable conditions for highly sensitive liquid chromatography-electrospray mass spectrometry glycan analysis in this work. 26452918 1 21 theme glycans 296:302 arg1 hydrophilicity 248:261 high hydrophilicity 243:261 high hydrophilicity 243:261 Labelling strategy plays an important role in mass spectrometry (MS) based glycan analysis due to the high hydrophilicity and low ionization efficiency of glycans. 26452918 1 21 theme glycans 296:302 arg1 efficiency 282:291 low ionization efficiency 267:291 low ionization efficiency 267:291 Labelling strategy plays an important role in mass spectrometry (MS) based glycan analysis due to the high hydrophilicity and low ionization efficiency of glycans. 26452918 3 22 theme response 661:668 arg1 aspect 619:624 aspect 619:624 aspect of the differently enhanced glycan response to mass spectrometry 619:689 Attached to N-glycans through non-reductive reactions, these new labelling reagents were evaluated in aspect of the differently enhanced glycan response to mass spectrometry. 26452918 1 23 theme based 210:214 arg1 analysis 223:230 mass spectrometry (MS) based glycan analysis 187:230 mass spectrometry (MS) based glycan analysis 187:230 Labelling strategy plays an important role in mass spectrometry (MS) based glycan analysis due to the high hydrophilicity and low ionization efficiency of glycans. 26452918 2 24 theme labelling 336:344 arg1 reagents 346:353 Ten hydrazino-s-triazine based labelling reagents 305:353 Ten hydrazino-s-triazine based labelling reagents 305:353 Ten hydrazino-s-triazine based labelling reagents were synthesized under facile and controllable conditions for highly sensitive liquid chromatography-electrospray mass spectrometry glycan analysis in this work. 26452918 1 25 theme glycan 216:221 arg1 analysis 223:230 mass spectrometry (MS) based glycan analysis 187:230 mass spectrometry (MS) based glycan analysis 187:230 Labelling strategy plays an important role in mass spectrometry (MS) based glycan analysis due to the high hydrophilicity and low ionization efficiency of glycans. 26452918 0 26 theme labelling 27:35 arg1 reagents 37:44 labelling reagents 27:44 labelling reagents for highly sensitive glycan analysis 27:81 Hydrazino-s-triazine based labelling reagents for highly sensitive glycan analysis via liquid chromatography-electrospray mass spectrometry. 26452918 5 27 theme chicken 1028:1034 arg1 avidin 1036:1041 chicken avidin 1028:1041 chicken avidin 1028:1041 Furthermore, the most optimal labelling reagent was taken as an example for highly sensitive profiling of N-linked glycans both cleaved from chicken avidin and glycoproteins in human serum, indicating prospective availability for these labelling reagents in frontier of glycomics researches. 26452918 1 28 dep hydrophilicity 248:261 arg1 the 239:241 the 239:241 the 239:241 Labelling strategy plays an important role in mass spectrometry (MS) based glycan analysis due to the high hydrophilicity and low ionization efficiency of glycans. 26452918 1 29 theme Labelling 141:149 arg1 strategy 151:158 Labelling strategy 141:158 Labelling strategy 141:158 Labelling strategy plays an important role in mass spectrometry (MS) based glycan analysis due to the high hydrophilicity and low ionization efficiency of glycans. 26452918 3 30 theme non-reductive 547:559 arg1 reactions 561:569 non-reductive reactions 547:569 non-reductive reactions 547:569 Attached to N-glycans through non-reductive reactions, these new labelling reagents were evaluated in aspect of the differently enhanced glycan response to mass spectrometry. 26452918 3 31 theme new 578:580 arg1 reagents 592:599 these new labelling reagents 572:599 these new labelling reagents 572:599 Attached to N-glycans through non-reductive reactions, these new labelling reagents were evaluated in aspect of the differently enhanced glycan response to mass spectrometry. 26452918 3 32 theme enhanced 645:652 arg1 response 661:668 the differently enhanced glycan response 629:668 the differently enhanced glycan response to mass spectrometry 629:689 Attached to N-glycans through non-reductive reactions, these new labelling reagents were evaluated in aspect of the differently enhanced glycan response to mass spectrometry. 26452918 2 33 theme sensitive 424:432 arg1 spectrometry 474:485 highly sensitive liquid chromatography-electrospray mass spectrometry 417:485 highly sensitive liquid chromatography-electrospray mass spectrometry glycan analysis 417:501 Ten hydrazino-s-triazine based labelling reagents were synthesized under facile and controllable conditions for highly sensitive liquid chromatography-electrospray mass spectrometry glycan analysis in this work. 26452918 2 34 theme glycan 487:492 arg1 analysis 494:501 highly sensitive liquid chromatography-electrospray mass spectrometry glycan analysis 417:501 highly sensitive liquid chromatography-electrospray mass spectrometry glycan analysis 417:501 Ten hydrazino-s-triazine based labelling reagents were synthesized under facile and controllable conditions for highly sensitive liquid chromatography-electrospray mass spectrometry glycan analysis in this work. 26452918 5 35 theme glycans 1002:1008 arg1 profiling 980:988 highly sensitive profiling 963:988 highly sensitive profiling of N-linked glycans 963:1008 Furthermore, the most optimal labelling reagent was taken as an example for highly sensitive profiling of N-linked glycans both cleaved from chicken avidin and glycoproteins in human serum, indicating prospective availability for these labelling reagents in frontier of glycomics researches. 26452918 2 36 theme spectrometry 474:485 arg1 analysis 494:501 highly sensitive liquid chromatography-electrospray mass spectrometry glycan analysis 417:501 highly sensitive liquid chromatography-electrospray mass spectrometry glycan analysis 417:501 Ten hydrazino-s-triazine based labelling reagents were synthesized under facile and controllable conditions for highly sensitive liquid chromatography-electrospray mass spectrometry glycan analysis in this work. 26452918 0 37 theme glycan 67:72 arg1 analysis 74:81 highly sensitive glycan analysis 50:81 highly sensitive glycan analysis 50:81 Hydrazino-s-triazine based labelling reagents for highly sensitive glycan analysis via liquid chromatography-electrospray mass spectrometry. 26452918 5 38 theme labelling 1123:1131 arg1 reagents 1133:1140 these labelling reagents 1117:1140 these labelling reagents 1117:1140 Furthermore, the most optimal labelling reagent was taken as an example for highly sensitive profiling of N-linked glycans both cleaved from chicken avidin and glycoproteins in human serum, indicating prospective availability for these labelling reagents in frontier of glycomics researches. 26452918 5 39 theme N-linked 993:1000 arg1 glycans 1002:1008 N-linked glycans 993:1008 N-linked glycans 993:1008 Furthermore, the most optimal labelling reagent was taken as an example for highly sensitive profiling of N-linked glycans both cleaved from chicken avidin and glycoproteins in human serum, indicating prospective availability for these labelling reagents in frontier of glycomics researches. 26452918 0 40 theme sensitive 57:65 arg1 analysis 74:81 highly sensitive glycan analysis 50:81 highly sensitive glycan analysis 50:81 Hydrazino-s-triazine based labelling reagents for highly sensitive glycan analysis via liquid chromatography-electrospray mass spectrometry. 26452918 3 41 theme mass 673:676 arg1 spectrometry 678:689 mass spectrometry 673:689 mass spectrometry 673:689 Attached to N-glycans through non-reductive reactions, these new labelling reagents were evaluated in aspect of the differently enhanced glycan response to mass spectrometry. 26452918 2 42 theme facile 378:383 arg1 conditions 402:411 facile and controllable conditions 378:411 facile and controllable conditions 378:411 Ten hydrazino-s-triazine based labelling reagents were synthesized under facile and controllable conditions for highly sensitive liquid chromatography-electrospray mass spectrometry glycan analysis in this work. 26452918 5 43 link N-linked 993:1000 arg1 glycans 1002:1008 N-linked glycans 993:1008 N-linked glycans 993:1008 Furthermore, the most optimal labelling reagent was taken as an example for highly sensitive profiling of N-linked glycans both cleaved from chicken avidin and glycoproteins in human serum, indicating prospective availability for these labelling reagents in frontier of glycomics researches. 26452918 5 44 dep taken 939:943 arg1 both 1010:1013 both 1010:1013 both 1010:1013 Furthermore, the most optimal labelling reagent was taken as an example for highly sensitive profiling of N-linked glycans both cleaved from chicken avidin and glycoproteins in human serum, indicating prospective availability for these labelling reagents in frontier of glycomics researches. 26452918 4 45 theme detection 841:849 arg1 limits 831:836 limits 831:836 limits of detection using maltoheptaose (DP7) as model 831:884 Three of the ten labelling reagents demonstrated to be reliable and remarkable for glycan analysis with satisfactory linearity and lowered limits of detection using maltoheptaose (DP7) as model. 26452918 1 46 theme important 169:177 arg1 role 179:182 an important role 166:182 an important role 166:182 Labelling strategy plays an important role in mass spectrometry (MS) based glycan analysis due to the high hydrophilicity and low ionization efficiency of glycans. 26452918 1 47 theme high 243:246 arg1 hydrophilicity 248:261 high hydrophilicity 243:261 high hydrophilicity 243:261 Labelling strategy plays an important role in mass spectrometry (MS) based glycan analysis due to the high hydrophilicity and low ionization efficiency of glycans. 26452918 5 48 theme glycomics 1157:1165 arg1 researches 1167:1176 glycomics researches 1157:1176 glycomics researches 1157:1176 Furthermore, the most optimal labelling reagent was taken as an example for highly sensitive profiling of N-linked glycans both cleaved from chicken avidin and glycoproteins in human serum, indicating prospective availability for these labelling reagents in frontier of glycomics researches. 26452918 5 49 theme prospective 1088:1098 arg1 availability 1100:1111 prospective availability 1088:1111 prospective availability for these labelling reagents in frontier of glycomics researches 1088:1176 Furthermore, the most optimal labelling reagent was taken as an example for highly sensitive profiling of N-linked glycans both cleaved from chicken avidin and glycoproteins in human serum, indicating prospective availability for these labelling reagents in frontier of glycomics researches. 26452918 4 50 theme reagents 719:726 arg1 reagents 719:726 the ten labelling reagents 701:726 the ten labelling reagents 701:726 Three of the ten labelling reagents demonstrated to be reliable and remarkable for glycan analysis with satisfactory linearity and lowered limits of detection using maltoheptaose (DP7) as model. 26452918 4 50 theme reagents 719:726 arg1 Three 692:696 Three 692:696 Three 692:696 Three of the ten labelling reagents demonstrated to be reliable and remarkable for glycan analysis with satisfactory linearity and lowered limits of detection using maltoheptaose (DP7) as model. 26452918 4 51 theme glycan 775:780 arg1 analysis 782:789 glycan analysis 775:789 glycan analysis with satisfactory linearity 775:817 Three of the ten labelling reagents demonstrated to be reliable and remarkable for glycan analysis with satisfactory linearity and lowered limits of detection using maltoheptaose (DP7) as model. 26452918 5 52 gly glycoproteins 1047:1059 arg1 glycoproteins 1047:1059 glycoproteins 1047:1059 glycoproteins 1047:1059 Furthermore, the most optimal labelling reagent was taken as an example for highly sensitive profiling of N-linked glycans both cleaved from chicken avidin and glycoproteins in human serum, indicating prospective availability for these labelling reagents in frontier of glycomics researches. 26452918 5 53 theme optimal 909:915 arg1 example 951:957 an example 948:957 an example for highly sensitive profiling of N-linked glycans 948:1008 Furthermore, the most optimal labelling reagent was taken as an example for highly sensitive profiling of N-linked glycans both cleaved from chicken avidin and glycoproteins in human serum, indicating prospective availability for these labelling reagents in frontier of glycomics researches. 26452918 5 53 theme optimal 909:915 arg1 reagent 927:933 the most optimal labelling reagent 900:933 the most optimal labelling reagent 900:933 Furthermore, the most optimal labelling reagent was taken as an example for highly sensitive profiling of N-linked glycans both cleaved from chicken avidin and glycoproteins in human serum, indicating prospective availability for these labelling reagents in frontier of glycomics researches. 26452918 5 54 theme sensitive 970:978 arg1 profiling 980:988 highly sensitive profiling 963:988 highly sensitive profiling of N-linked glycans 963:1008 Furthermore, the most optimal labelling reagent was taken as an example for highly sensitive profiling of N-linked glycans both cleaved from chicken avidin and glycoproteins in human serum, indicating prospective availability for these labelling reagents in frontier of glycomics researches. 26452918 4 55 theme satisfactory 796:807 arg1 linearity 809:817 satisfactory linearity 796:817 satisfactory linearity 796:817 Three of the ten labelling reagents demonstrated to be reliable and remarkable for glycan analysis with satisfactory linearity and lowered limits of detection using maltoheptaose (DP7) as model. 28510840 6 0 theme strong 1059:1064 arg1 tolerance 1071:1079 the strong salt tolerance 1055:1079 the strong salt tolerance 1055:1079 Spartina alterniflora is widely used for shoreline protection and tidal marsh restoration due to the strong salt tolerance although the exact molecular mechanism is little known. 28510840 4 1 with OST 649:651 arg1 isoforms 683:690 different catalytic STT3 isoforms 658:690 different catalytic STT3 isoforms 658:690 OST with different catalytic STT3 isoforms has different enzymatic properties in mammals. 28510840 14 2 theme N-glycosylation 2455:2469 arg1 process 2471:2477 a similar N-glycosylation process 2445:2477 a similar N-glycosylation process 2445:2477 Moreover, SaSTT3 genes could successfully rescue Arabidopsis stt3a-2 salt-sensitive phenotype, suggesting there exists a similar N-glycosylation process in S. alterniflora. 28510840 2 3 theme Biochemical 354:364 arg1 assay 378:382 Biochemical and genetic assay 354:382 Biochemical and genetic assay 354:382 Biochemical and genetic assay leads to the identification of the nine subunits (Ost 1-6, Stt3, Swp1 and Wbp1) of the yeast OST and in which Stt3p is proposed playing a central and conserved role in N-glycosylation. 28510840 1 4 theme endoplasmic 267:277 arg1 ER 290:291 ER 290:291 ER 290:291 BACKGROUND Asparagine (N)-linked glycosylation is one of the most crucial post-translational modifications, which is catalyzed in the lumen of the endoplasmic reticulum (ER) by the oligosaccharyltransferase (OST) in eukaryotic cells. 28510840 1 4 theme endoplasmic 267:277 arg1 reticulum 279:287 the endoplasmic reticulum 263:287 the endoplasmic reticulum (ER) 263:292 BACKGROUND Asparagine (N)-linked glycosylation is one of the most crucial post-translational modifications, which is catalyzed in the lumen of the endoplasmic reticulum (ER) by the oligosaccharyltransferase (OST) in eukaryotic cells. 28510840 1 5 theme crucial 186:192 arg1 modifications 213:225 the most crucial post-translational modifications 177:225 the most crucial post-translational modifications 177:225 BACKGROUND Asparagine (N)-linked glycosylation is one of the most crucial post-translational modifications, which is catalyzed in the lumen of the endoplasmic reticulum (ER) by the oligosaccharyltransferase (OST) in eukaryotic cells. 28510840 12 6 theme STT3A 1990:1994 arg1 functions 1996:2004 STT3A functions 1990:2004 STT3A functions conservatively between glycophyte and halophyte and N-glycosylation 1990:2072 The functional complementation in which the cDNA of SaSTT3A and SaSTT3B driven by CaMV 35S promoter completely or partially rescued Arabidopsis stt3a-2 mutant salt-sensitive phenotype, indicating STT3A functions conservatively between glycophyte and halophyte and N-glycosylation might be involved in plant resistance to salinity. 28510840 10 7 theme gene 1571:1574 arg1 structures 1576:1585 The gene structures 1567:1585 The gene structures of both genes 1567:1599 The gene structures of both genes were conserved among the analyzed plant species. 28510840 1 8 theme modifications 213:225 arg1 one 170:172 one 170:172 one 170:172 BACKGROUND Asparagine (N)-linked glycosylation is one of the most crucial post-translational modifications, which is catalyzed in the lumen of the endoplasmic reticulum (ER) by the oligosaccharyltransferase (OST) in eukaryotic cells. 28510840 1 8 theme modifications 213:225 arg1 modifications 213:225 the most crucial post-translational modifications 177:225 the most crucial post-translational modifications 177:225 BACKGROUND Asparagine (N)-linked glycosylation is one of the most crucial post-translational modifications, which is catalyzed in the lumen of the endoplasmic reticulum (ER) by the oligosaccharyltransferase (OST) in eukaryotic cells. 28510840 11 9 contain had 1744:1746 arg2 helices 1772:1778 13 and 11 transmembrane helices 1748:1778 helices 1772:1778 Subcellular localization and transmembrane structure prediction revealed that these two genes had 13 and 11 transmembrane helices respectively. 28510840 11 9 contain had 1744:1746 arg1 genes 1738:1742 these two genes 1728:1742 these two genes 1728:1742 Subcellular localization and transmembrane structure prediction revealed that these two genes had 13 and 11 transmembrane helices respectively. 28510840 9 10 theme SaSTT3A 1462:1468 arg1 sequences 1478:1486 SaSTT3A genomic sequences 1462:1486 SaSTT3A genomic sequences 1462:1486 SaSTT3A genomic sequences spanned over 23 exons and 22 introns, while SaSTT3B had 6 exons and 5 introns. 28510840 12 11 theme salt-sensitive 1953:1966 arg1 phenotype 1968:1976 Arabidopsis stt3a-2 mutant salt-sensitive phenotype 1926:1976 Arabidopsis stt3a-2 mutant salt-sensitive phenotype 1926:1976 The functional complementation in which the cDNA of SaSTT3A and SaSTT3B driven by CaMV 35S promoter completely or partially rescued Arabidopsis stt3a-2 mutant salt-sensitive phenotype, indicating STT3A functions conservatively between glycophyte and halophyte and N-glycosylation might be involved in plant resistance to salinity. 28510840 10 12 theme genes 1595:1599 arg1 structures 1576:1585 The gene structures 1567:1585 The gene structures of both genes 1567:1599 The gene structures of both genes were conserved among the analyzed plant species. 28510840 5 13 theme STT3A 755:759 arg1 mutation 743:750 The mutation 739:750 The mutation of STT3A in Arabidopsis thaliana 739:783 The mutation of STT3A in Arabidopsis thaliana causes a salt hypersensitive phenotype the inhibited root growth and swollen root tips suggesting protein N-glycosylation is indispensable for plant growth and development. 28510840 4 14 contain has 692:694 arg2 properties 716:725 different enzymatic properties 696:725 different enzymatic properties 696:725 OST with different catalytic STT3 isoforms has different enzymatic properties in mammals. 28510840 4 14 contain has 692:694 arg1 OST 649:651 OST 649:651 OST with different catalytic STT3 isoforms 649:690 OST with different catalytic STT3 isoforms has different enzymatic properties in mammals. 28510840 15 15 theme evidence 2533:2540 arg1 piece 2524:2528 a first piece 2516:2528 a first piece of evidence 2516:2540 Here we provided a first piece of evidence that the N-glycosylation might be involved in salt tolerance of halophyte. 28510840 5 16 theme root 862:865 arg1 tips 867:870 swollen root tips 854:870 swollen root tips 854:870 The mutation of STT3A in Arabidopsis thaliana causes a salt hypersensitive phenotype the inhibited root growth and swollen root tips suggesting protein N-glycosylation is indispensable for plant growth and development. 28510840 7 17 theme Arabidopsis 1329:1339 arg1 mutant 1341:1346 Arabidopsis mutant 1329:1346 Arabidopsis mutant to observe the functional conservation 1329:1385 To explore the possible biological roles of N-glycosylation in plant adaptive resistance to salinity stress, we cloned the STT3 genes from S. alterniflora and heterogenously expressed them in Arabidopsis mutant to observe the functional conservation. 28510840 14 18 theme stt3a-2 2387:2393 arg1 phenotype 2410:2418 Arabidopsis stt3a-2 salt-sensitive phenotype 2375:2418 Arabidopsis stt3a-2 salt-sensitive phenotype 2375:2418 Moreover, SaSTT3 genes could successfully rescue Arabidopsis stt3a-2 salt-sensitive phenotype, suggesting there exists a similar N-glycosylation process in S. alterniflora. 28510840 13 19 theme isoform 2146:2152 arg1 SaSTT3A 2161:2167 SaSTT3A 2161:2167 SaSTT3A 2161:2167 CONCLUSIONS Two STT3 isoform genes, SaSTT3A and SaSTT3B, were cloned from S. alterniflora and they were evolutionally conserved at gene structure and coding sequences compared with their counterparts. 28510840 13 19 theme isoform 2146:2152 arg1 genes 2154:2158 CONCLUSIONS Two STT3 isoform genes 2125:2158 CONCLUSIONS Two STT3 isoform genes 2125:2158 CONCLUSIONS Two STT3 isoform genes, SaSTT3A and SaSTT3B, were cloned from S. alterniflora and they were evolutionally conserved at gene structure and coding sequences compared with their counterparts. 28510840 13 19 theme isoform 2146:2152 arg1 SaSTT3B 2173:2179 SaSTT3B 2173:2179 SaSTT3B 2173:2179 CONCLUSIONS Two STT3 isoform genes, SaSTT3A and SaSTT3B, were cloned from S. alterniflora and they were evolutionally conserved at gene structure and coding sequences compared with their counterparts. 28510840 3 20 theme isoform 578:584 arg1 STT3A 593:597 STT3A 593:597 STT3A 593:597 Two STT3 isoform genes, STT3A and STT3B, exist in the plant and mammal genomes. 28510840 3 20 theme isoform 578:584 arg1 genes 586:590 Two STT3 isoform genes 569:590 Two STT3 isoform genes 569:590 Two STT3 isoform genes, STT3A and STT3B, exist in the plant and mammal genomes. 28510840 3 20 theme isoform 578:584 arg1 STT3B 603:607 STT3B 603:607 STT3B 603:607 Two STT3 isoform genes, STT3A and STT3B, exist in the plant and mammal genomes. 28510840 7 21 theme adaptive 1206:1213 arg1 resistance 1215:1224 plant adaptive resistance 1200:1224 plant adaptive resistance to salinity stress 1200:1243 To explore the possible biological roles of N-glycosylation in plant adaptive resistance to salinity stress, we cloned the STT3 genes from S. alterniflora and heterogenously expressed them in Arabidopsis mutant to observe the functional conservation. 28510840 8 22 dep RESULTS 1388:1394 arg1 SaSTT3A 1396:1402 SaSTT3A 1396:1402 SaSTT3A 1396:1402 RESULTS SaSTT3A and SaSTT3B genes were cloned from Spartina alterniflora. 28510840 8 22 dep RESULTS 1388:1394 arg1 genes 1416:1420 SaSTT3B genes 1408:1420 SaSTT3B genes 1408:1420 RESULTS SaSTT3A and SaSTT3B genes were cloned from Spartina alterniflora. 28510840 11 23 theme transmembrane 1758:1770 arg1 helices 1772:1778 13 and 11 transmembrane helices 1748:1778 helices 1772:1778 Subcellular localization and transmembrane structure prediction revealed that these two genes had 13 and 11 transmembrane helices respectively. 28510840 6 24 theme Spartina 958:965 arg1 alterniflora 967:978 Spartina alterniflora 958:978 Spartina alterniflora 958:978 Spartina alterniflora is widely used for shoreline protection and tidal marsh restoration due to the strong salt tolerance although the exact molecular mechanism is little known. 28510840 4 25 theme different 696:704 arg1 properties 716:725 different enzymatic properties 696:725 different enzymatic properties 696:725 OST with different catalytic STT3 isoforms has different enzymatic properties in mammals. 28510840 4 26 theme STT3 678:681 arg1 isoforms 683:690 different catalytic STT3 isoforms 658:690 different catalytic STT3 isoforms 658:690 OST with different catalytic STT3 isoforms has different enzymatic properties in mammals. 28510840 12 27 theme Arabidopsis 1926:1936 arg1 phenotype 1968:1976 Arabidopsis stt3a-2 mutant salt-sensitive phenotype 1926:1976 Arabidopsis stt3a-2 mutant salt-sensitive phenotype 1926:1976 The functional complementation in which the cDNA of SaSTT3A and SaSTT3B driven by CaMV 35S promoter completely or partially rescued Arabidopsis stt3a-2 mutant salt-sensitive phenotype, indicating STT3A functions conservatively between glycophyte and halophyte and N-glycosylation might be involved in plant resistance to salinity. 28510840 15 28 theme salt 2588:2591 arg1 tolerance 2593:2601 salt tolerance 2588:2601 salt tolerance of halophyte 2588:2614 Here we provided a first piece of evidence that the N-glycosylation might be involved in salt tolerance of halophyte. 28510840 5 29 theme plant 928:932 arg1 growth 934:939 plant growth 928:939 plant growth 928:939 The mutation of STT3A in Arabidopsis thaliana causes a salt hypersensitive phenotype the inhibited root growth and swollen root tips suggesting protein N-glycosylation is indispensable for plant growth and development. 28510840 2 30 theme OST 477:479 arg1 subunits 424:431 the nine subunits 415:431 the nine subunits (Ost 1-6, Stt3, Swp1 and Wbp1) of the yeast OST and in which Stt3p is proposed playing a central and conserved role in N-glycosylation 415:566 Biochemical and genetic assay leads to the identification of the nine subunits (Ost 1-6, Stt3, Swp1 and Wbp1) of the yeast OST and in which Stt3p is proposed playing a central and conserved role in N-glycosylation. 28510840 10 31 theme analyzed 1626:1633 arg1 species 1641:1647 the analyzed plant species 1622:1647 the analyzed plant species 1622:1647 The gene structures of both genes were conserved among the analyzed plant species. 28510840 7 32 theme biological 1161:1170 arg1 roles 1172:1176 the possible biological roles 1148:1176 the possible biological roles of N-glycosylation in plant adaptive resistance to salinity stress 1148:1243 To explore the possible biological roles of N-glycosylation in plant adaptive resistance to salinity stress, we cloned the STT3 genes from S. alterniflora and heterogenously expressed them in Arabidopsis mutant to observe the functional conservation. 28510840 5 33 from mutation 743:750 arg1 thaliana 776:783 Arabidopsis thaliana 764:783 Arabidopsis thaliana 764:783 The mutation of STT3A in Arabidopsis thaliana causes a salt hypersensitive phenotype the inhibited root growth and swollen root tips suggesting protein N-glycosylation is indispensable for plant growth and development. 28510840 12 34 theme 35S 1881:1883 arg1 promoter 1885:1892 CaMV 35S promoter 1876:1892 CaMV 35S promoter 1876:1892 The functional complementation in which the cDNA of SaSTT3A and SaSTT3B driven by CaMV 35S promoter completely or partially rescued Arabidopsis stt3a-2 mutant salt-sensitive phenotype, indicating STT3A functions conservatively between glycophyte and halophyte and N-glycosylation might be involved in plant resistance to salinity. 28510840 4 35 theme catalytic 668:676 arg1 isoforms 683:690 different catalytic STT3 isoforms 658:690 different catalytic STT3 isoforms 658:690 OST with different catalytic STT3 isoforms has different enzymatic properties in mammals. 28510840 13 36 theme gene 2256:2259 arg1 structure 2261:2269 gene structure 2256:2269 gene structure 2256:2269 CONCLUSIONS Two STT3 isoform genes, SaSTT3A and SaSTT3B, were cloned from S. alterniflora and they were evolutionally conserved at gene structure and coding sequences compared with their counterparts. 28510840 6 37 theme marsh 1030:1034 arg1 restoration 1036:1046 tidal marsh restoration 1024:1046 tidal marsh restoration 1024:1046 Spartina alterniflora is widely used for shoreline protection and tidal marsh restoration due to the strong salt tolerance although the exact molecular mechanism is little known. 28510840 2 38 theme Ost 434:436 arg1 1-6 438:440 Ost 1-6 434:440 Ost 1-6 434:440 Biochemical and genetic assay leads to the identification of the nine subunits (Ost 1-6, Stt3, Swp1 and Wbp1) of the yeast OST and in which Stt3p is proposed playing a central and conserved role in N-glycosylation. 28510840 2 39 theme subunits 424:431 arg1 identification 397:410 the identification 393:410 the identification of the nine subunits (Ost 1-6, Stt3, Swp1 and Wbp1) of the yeast OST and in which Stt3p is proposed playing a central and conserved role in N-glycosylation 393:566 Biochemical and genetic assay leads to the identification of the nine subunits (Ost 1-6, Stt3, Swp1 and Wbp1) of the yeast OST and in which Stt3p is proposed playing a central and conserved role in N-glycosylation. 28510840 0 40 theme oligosaccharyltransferase 14:38 arg1 subunits 50:57 Two conserved oligosaccharyltransferase catalytic subunits 0:57 Two conserved oligosaccharyltransferase catalytic subunits required for N-glycosylation 0:86 Two conserved oligosaccharyltransferase catalytic subunits required for N-glycosylation exist in Spartina alterniflora. 28510840 12 41 theme SaSTT3B 1858:1864 arg1 cDNA 1838:1841 the cDNA 1834:1841 the cDNA of SaSTT3A and SaSTT3B driven by CaMV 35S promoter 1834:1892 The functional complementation in which the cDNA of SaSTT3A and SaSTT3B driven by CaMV 35S promoter completely or partially rescued Arabidopsis stt3a-2 mutant salt-sensitive phenotype, indicating STT3A functions conservatively between glycophyte and halophyte and N-glycosylation might be involved in plant resistance to salinity. 28510840 11 42 theme structure 1693:1701 arg1 prediction 1703:1712 transmembrane structure prediction 1679:1712 transmembrane structure prediction 1679:1712 Subcellular localization and transmembrane structure prediction revealed that these two genes had 13 and 11 transmembrane helices respectively. 28510840 5 43 dep phenotype 814:822 arg1 growth 843:848 the inhibited root growth 824:848 the inhibited root growth 824:848 The mutation of STT3A in Arabidopsis thaliana causes a salt hypersensitive phenotype the inhibited root growth and swollen root tips suggesting protein N-glycosylation is indispensable for plant growth and development. 28510840 5 44 theme salt 794:797 arg1 phenotype 814:822 a salt hypersensitive phenotype 792:822 a salt hypersensitive phenotype 792:822 The mutation of STT3A in Arabidopsis thaliana causes a salt hypersensitive phenotype the inhibited root growth and swollen root tips suggesting protein N-glycosylation is indispensable for plant growth and development. 28510840 6 45 theme shoreline 999:1007 arg1 protection 1009:1018 shoreline protection 999:1018 shoreline protection 999:1018 Spartina alterniflora is widely used for shoreline protection and tidal marsh restoration due to the strong salt tolerance although the exact molecular mechanism is little known. 28510840 1 46 link -linked 145:151 arg1 glycosylation 153:165 BACKGROUND Asparagine (N)-linked glycosylation 120:165 BACKGROUND Asparagine (N)-linked glycosylation 120:165 BACKGROUND Asparagine (N)-linked glycosylation is one of the most crucial post-translational modifications, which is catalyzed in the lumen of the endoplasmic reticulum (ER) by the oligosaccharyltransferase (OST) in eukaryotic cells. 28510840 2 47 dep subunits 424:431 arg1 1-6 438:440 Ost 1-6 434:440 Ost 1-6 434:440 Biochemical and genetic assay leads to the identification of the nine subunits (Ost 1-6, Stt3, Swp1 and Wbp1) of the yeast OST and in which Stt3p is proposed playing a central and conserved role in N-glycosylation. 28510840 2 47 dep subunits 424:431 arg1 Wbp1 458:461 Wbp1 458:461 Wbp1 458:461 Biochemical and genetic assay leads to the identification of the nine subunits (Ost 1-6, Stt3, Swp1 and Wbp1) of the yeast OST and in which Stt3p is proposed playing a central and conserved role in N-glycosylation. 28510840 2 47 dep subunits 424:431 arg1 Swp1 449:452 Swp1 449:452 Swp1 449:452 Biochemical and genetic assay leads to the identification of the nine subunits (Ost 1-6, Stt3, Swp1 and Wbp1) of the yeast OST and in which Stt3p is proposed playing a central and conserved role in N-glycosylation. 28510840 2 47 dep subunits 424:431 arg1 Stt3 443:446 Stt3 443:446 Stt3 443:446 Biochemical and genetic assay leads to the identification of the nine subunits (Ost 1-6, Stt3, Swp1 and Wbp1) of the yeast OST and in which Stt3p is proposed playing a central and conserved role in N-glycosylation. 28510840 6 48 theme exact 1094:1098 arg1 little 1123:1128 little 1123:1128 little 1123:1128 Spartina alterniflora is widely used for shoreline protection and tidal marsh restoration due to the strong salt tolerance although the exact molecular mechanism is little known. 28510840 6 48 theme exact 1094:1098 arg1 mechanism 1110:1118 the exact molecular mechanism 1090:1118 the exact molecular mechanism 1090:1118 Spartina alterniflora is widely used for shoreline protection and tidal marsh restoration due to the strong salt tolerance although the exact molecular mechanism is little known. 28510840 8 49 theme SaSTT3B 1408:1414 arg1 genes 1416:1420 SaSTT3B genes 1408:1420 SaSTT3B genes 1408:1420 RESULTS SaSTT3A and SaSTT3B genes were cloned from Spartina alterniflora. 28510840 12 50 theme SaSTT3A 1846:1852 arg1 cDNA 1838:1841 the cDNA 1834:1841 the cDNA of SaSTT3A and SaSTT3B driven by CaMV 35S promoter 1834:1892 The functional complementation in which the cDNA of SaSTT3A and SaSTT3B driven by CaMV 35S promoter completely or partially rescued Arabidopsis stt3a-2 mutant salt-sensitive phenotype, indicating STT3A functions conservatively between glycophyte and halophyte and N-glycosylation might be involved in plant resistance to salinity. 28510840 5 51 theme root 838:841 arg1 growth 843:848 the inhibited root growth 824:848 the inhibited root growth 824:848 The mutation of STT3A in Arabidopsis thaliana causes a salt hypersensitive phenotype the inhibited root growth and swollen root tips suggesting protein N-glycosylation is indispensable for plant growth and development. 28510840 5 52 theme hypersensitive 799:812 arg1 phenotype 814:822 a salt hypersensitive phenotype 792:822 a salt hypersensitive phenotype 792:822 The mutation of STT3A in Arabidopsis thaliana causes a salt hypersensitive phenotype the inhibited root growth and swollen root tips suggesting protein N-glycosylation is indispensable for plant growth and development. 28510840 12 53 theme functional 1798:1807 arg1 complementation 1809:1823 The functional complementation 1794:1823 The functional complementation in which the cDNA of SaSTT3A and SaSTT3B driven by CaMV 35S promoter completely or partially rescued Arabidopsis stt3a-2 mutant salt-sensitive phenotype, indicating STT3A functions conservatively between glycophyte and halophyte and N-glycosylation might be involved in plant resistance to salinity. 1794:2123 The functional complementation in which the cDNA of SaSTT3A and SaSTT3B driven by CaMV 35S promoter completely or partially rescued Arabidopsis stt3a-2 mutant salt-sensitive phenotype, indicating STT3A functions conservatively between glycophyte and halophyte and N-glycosylation might be involved in plant resistance to salinity. 28510840 6 54 theme salt 1066:1069 arg1 tolerance 1071:1079 the strong salt tolerance 1055:1079 the strong salt tolerance 1055:1079 Spartina alterniflora is widely used for shoreline protection and tidal marsh restoration due to the strong salt tolerance although the exact molecular mechanism is little known. 28510840 3 55 theme mammal 633:638 arg1 genomes 640:646 the plant and mammal genomes 619:646 the plant and mammal genomes 619:646 Two STT3 isoform genes, STT3A and STT3B, exist in the plant and mammal genomes. 28510840 3 56 theme plant 623:627 arg1 genomes 640:646 the plant and mammal genomes 619:646 the plant and mammal genomes 619:646 Two STT3 isoform genes, STT3A and STT3B, exist in the plant and mammal genomes. 28510840 1 57 from oligosaccharyltransferase 301:325 arg1 cells 347:351 eukaryotic cells 336:351 eukaryotic cells 336:351 BACKGROUND Asparagine (N)-linked glycosylation is one of the most crucial post-translational modifications, which is catalyzed in the lumen of the endoplasmic reticulum (ER) by the oligosaccharyltransferase (OST) in eukaryotic cells. 28510840 14 58 theme similar 2447:2453 arg1 process 2471:2477 a similar N-glycosylation process 2445:2477 a similar N-glycosylation process 2445:2477 Moreover, SaSTT3 genes could successfully rescue Arabidopsis stt3a-2 salt-sensitive phenotype, suggesting there exists a similar N-glycosylation process in S. alterniflora. 28510840 1 59 theme reticulum 279:287 arg1 lumen 254:258 the lumen 250:258 the lumen of the endoplasmic reticulum (ER) 250:292 BACKGROUND Asparagine (N)-linked glycosylation is one of the most crucial post-translational modifications, which is catalyzed in the lumen of the endoplasmic reticulum (ER) by the oligosaccharyltransferase (OST) in eukaryotic cells. 28510840 2 60 theme conserved 534:542 arg1 role 544:547 a central and conserved role 520:547 a central and conserved role 520:547 Biochemical and genetic assay leads to the identification of the nine subunits (Ost 1-6, Stt3, Swp1 and Wbp1) of the yeast OST and in which Stt3p is proposed playing a central and conserved role in N-glycosylation. 28510840 11 61 theme Subcellular 1650:1660 arg1 localization 1662:1673 Subcellular localization 1650:1673 Subcellular localization 1650:1673 Subcellular localization and transmembrane structure prediction revealed that these two genes had 13 and 11 transmembrane helices respectively. 28510840 1 62 theme most 181:184 arg1 modifications 213:225 the most crucial post-translational modifications 177:225 the most crucial post-translational modifications 177:225 BACKGROUND Asparagine (N)-linked glycosylation is one of the most crucial post-translational modifications, which is catalyzed in the lumen of the endoplasmic reticulum (ER) by the oligosaccharyltransferase (OST) in eukaryotic cells. 28510840 6 63 used used 990:993 arg2 alterniflora 967:978 Spartina alterniflora 958:978 Spartina alterniflora 958:978 Spartina alterniflora is widely used for shoreline protection and tidal marsh restoration due to the strong salt tolerance although the exact molecular mechanism is little known. 28510840 1 64 theme post-translational 194:211 arg1 modifications 213:225 the most crucial post-translational modifications 177:225 the most crucial post-translational modifications 177:225 BACKGROUND Asparagine (N)-linked glycosylation is one of the most crucial post-translational modifications, which is catalyzed in the lumen of the endoplasmic reticulum (ER) by the oligosaccharyltransferase (OST) in eukaryotic cells. 28510840 5 65 theme Arabidopsis 764:774 arg1 thaliana 776:783 Arabidopsis thaliana 764:783 Arabidopsis thaliana 764:783 The mutation of STT3A in Arabidopsis thaliana causes a salt hypersensitive phenotype the inhibited root growth and swollen root tips suggesting protein N-glycosylation is indispensable for plant growth and development. 28510840 9 66 theme genomic 1470:1476 arg1 sequences 1478:1486 SaSTT3A genomic sequences 1462:1486 SaSTT3A genomic sequences 1462:1486 SaSTT3A genomic sequences spanned over 23 exons and 22 introns, while SaSTT3B had 6 exons and 5 introns. 28510840 12 67 theme mutant 1946:1951 arg1 phenotype 1968:1976 Arabidopsis stt3a-2 mutant salt-sensitive phenotype 1926:1976 Arabidopsis stt3a-2 mutant salt-sensitive phenotype 1926:1976 The functional complementation in which the cDNA of SaSTT3A and SaSTT3B driven by CaMV 35S promoter completely or partially rescued Arabidopsis stt3a-2 mutant salt-sensitive phenotype, indicating STT3A functions conservatively between glycophyte and halophyte and N-glycosylation might be involved in plant resistance to salinity. 28510840 7 68 from roles 1172:1176 arg1 resistance 1215:1224 plant adaptive resistance 1200:1224 plant adaptive resistance to salinity stress 1200:1243 To explore the possible biological roles of N-glycosylation in plant adaptive resistance to salinity stress, we cloned the STT3 genes from S. alterniflora and heterogenously expressed them in Arabidopsis mutant to observe the functional conservation. 28510840 7 69 theme functional 1363:1372 arg1 conservation 1374:1385 the functional conservation 1359:1385 the functional conservation 1359:1385 To explore the possible biological roles of N-glycosylation in plant adaptive resistance to salinity stress, we cloned the STT3 genes from S. alterniflora and heterogenously expressed them in Arabidopsis mutant to observe the functional conservation. 28510840 5 70 theme swollen 854:860 arg1 tips 867:870 swollen root tips 854:870 swollen root tips 854:870 The mutation of STT3A in Arabidopsis thaliana causes a salt hypersensitive phenotype the inhibited root growth and swollen root tips suggesting protein N-glycosylation is indispensable for plant growth and development. 28510840 2 71 theme central 522:528 arg1 role 544:547 a central and conserved role 520:547 a central and conserved role 520:547 Biochemical and genetic assay leads to the identification of the nine subunits (Ost 1-6, Stt3, Swp1 and Wbp1) of the yeast OST and in which Stt3p is proposed playing a central and conserved role in N-glycosylation. 28510840 14 72 theme salt-sensitive 2395:2408 arg1 phenotype 2410:2418 Arabidopsis stt3a-2 salt-sensitive phenotype 2375:2418 Arabidopsis stt3a-2 salt-sensitive phenotype 2375:2418 Moreover, SaSTT3 genes could successfully rescue Arabidopsis stt3a-2 salt-sensitive phenotype, suggesting there exists a similar N-glycosylation process in S. alterniflora. 28510840 13 73 theme STT3 2141:2144 arg1 SaSTT3A 2161:2167 SaSTT3A 2161:2167 SaSTT3A 2161:2167 CONCLUSIONS Two STT3 isoform genes, SaSTT3A and SaSTT3B, were cloned from S. alterniflora and they were evolutionally conserved at gene structure and coding sequences compared with their counterparts. 28510840 13 73 theme STT3 2141:2144 arg1 genes 2154:2158 CONCLUSIONS Two STT3 isoform genes 2125:2158 CONCLUSIONS Two STT3 isoform genes 2125:2158 CONCLUSIONS Two STT3 isoform genes, SaSTT3A and SaSTT3B, were cloned from S. alterniflora and they were evolutionally conserved at gene structure and coding sequences compared with their counterparts. 28510840 13 73 theme STT3 2141:2144 arg1 SaSTT3B 2173:2179 SaSTT3B 2173:2179 SaSTT3B 2173:2179 CONCLUSIONS Two STT3 isoform genes, SaSTT3A and SaSTT3B, were cloned from S. alterniflora and they were evolutionally conserved at gene structure and coding sequences compared with their counterparts. 28510840 3 74 theme STT3 573:576 arg1 STT3A 593:597 STT3A 593:597 STT3A 593:597 Two STT3 isoform genes, STT3A and STT3B, exist in the plant and mammal genomes. 28510840 3 74 theme STT3 573:576 arg1 genes 586:590 Two STT3 isoform genes 569:590 Two STT3 isoform genes 569:590 Two STT3 isoform genes, STT3A and STT3B, exist in the plant and mammal genomes. 28510840 3 74 theme STT3 573:576 arg1 STT3B 603:607 STT3B 603:607 STT3B 603:607 Two STT3 isoform genes, STT3A and STT3B, exist in the plant and mammal genomes. 28510840 1 75 theme -linked 145:151 arg1 glycosylation 153:165 BACKGROUND Asparagine (N)-linked glycosylation 120:165 BACKGROUND Asparagine (N)-linked glycosylation 120:165 BACKGROUND Asparagine (N)-linked glycosylation is one of the most crucial post-translational modifications, which is catalyzed in the lumen of the endoplasmic reticulum (ER) by the oligosaccharyltransferase (OST) in eukaryotic cells. 28510840 14 76 theme Arabidopsis 2375:2385 arg1 phenotype 2410:2418 Arabidopsis stt3a-2 salt-sensitive phenotype 2375:2418 Arabidopsis stt3a-2 salt-sensitive phenotype 2375:2418 Moreover, SaSTT3 genes could successfully rescue Arabidopsis stt3a-2 salt-sensitive phenotype, suggesting there exists a similar N-glycosylation process in S. alterniflora. 28510840 11 77 theme 13 1748:1749 arg1 helices 1772:1778 13 and 11 transmembrane helices 1748:1778 helices 1772:1778 Subcellular localization and transmembrane structure prediction revealed that these two genes had 13 and 11 transmembrane helices respectively. 28510840 7 78 theme plant 1200:1204 arg1 resistance 1215:1224 plant adaptive resistance 1200:1224 plant adaptive resistance to salinity stress 1200:1243 To explore the possible biological roles of N-glycosylation in plant adaptive resistance to salinity stress, we cloned the STT3 genes from S. alterniflora and heterogenously expressed them in Arabidopsis mutant to observe the functional conservation. 28510840 14 79 theme SaSTT3 2336:2341 arg1 genes 2343:2347 SaSTT3 genes 2336:2347 SaSTT3 genes 2336:2347 Moreover, SaSTT3 genes could successfully rescue Arabidopsis stt3a-2 salt-sensitive phenotype, suggesting there exists a similar N-glycosylation process in S. alterniflora. 28510840 5 80 theme inhibited 828:836 arg1 growth 843:848 the inhibited root growth 824:848 the inhibited root growth 824:848 The mutation of STT3A in Arabidopsis thaliana causes a salt hypersensitive phenotype the inhibited root growth and swollen root tips suggesting protein N-glycosylation is indispensable for plant growth and development. 28510840 7 81 theme N-glycosylation 1181:1195 arg1 roles 1172:1176 the possible biological roles 1148:1176 the possible biological roles of N-glycosylation in plant adaptive resistance to salinity stress 1148:1243 To explore the possible biological roles of N-glycosylation in plant adaptive resistance to salinity stress, we cloned the STT3 genes from S. alterniflora and heterogenously expressed them in Arabidopsis mutant to observe the functional conservation. 28510840 1 82 theme eukaryotic 336:345 arg1 cells 347:351 eukaryotic cells 336:351 eukaryotic cells 336:351 BACKGROUND Asparagine (N)-linked glycosylation is one of the most crucial post-translational modifications, which is catalyzed in the lumen of the endoplasmic reticulum (ER) by the oligosaccharyltransferase (OST) in eukaryotic cells. 28510840 15 83 theme first 2518:2522 arg1 piece 2524:2528 a first piece 2516:2528 a first piece of evidence 2516:2540 Here we provided a first piece of evidence that the N-glycosylation might be involved in salt tolerance of halophyte. 28510840 12 84 theme plant 2095:2099 arg1 resistance 2101:2110 plant resistance 2095:2110 plant resistance to salinity 2095:2122 The functional complementation in which the cDNA of SaSTT3A and SaSTT3B driven by CaMV 35S promoter completely or partially rescued Arabidopsis stt3a-2 mutant salt-sensitive phenotype, indicating STT3A functions conservatively between glycophyte and halophyte and N-glycosylation might be involved in plant resistance to salinity. 28510840 13 85 theme CONCLUSIONS 2125:2135 arg1 SaSTT3A 2161:2167 SaSTT3A 2161:2167 SaSTT3A 2161:2167 CONCLUSIONS Two STT3 isoform genes, SaSTT3A and SaSTT3B, were cloned from S. alterniflora and they were evolutionally conserved at gene structure and coding sequences compared with their counterparts. 28510840 13 85 theme CONCLUSIONS 2125:2135 arg1 genes 2154:2158 CONCLUSIONS Two STT3 isoform genes 2125:2158 CONCLUSIONS Two STT3 isoform genes 2125:2158 CONCLUSIONS Two STT3 isoform genes, SaSTT3A and SaSTT3B, were cloned from S. alterniflora and they were evolutionally conserved at gene structure and coding sequences compared with their counterparts. 28510840 13 85 theme CONCLUSIONS 2125:2135 arg1 SaSTT3B 2173:2179 SaSTT3B 2173:2179 SaSTT3B 2173:2179 CONCLUSIONS Two STT3 isoform genes, SaSTT3A and SaSTT3B, were cloned from S. alterniflora and they were evolutionally conserved at gene structure and coding sequences compared with their counterparts. 28510840 12 86 theme stt3a-2 1938:1944 arg1 phenotype 1968:1976 Arabidopsis stt3a-2 mutant salt-sensitive phenotype 1926:1976 Arabidopsis stt3a-2 mutant salt-sensitive phenotype 1926:1976 The functional complementation in which the cDNA of SaSTT3A and SaSTT3B driven by CaMV 35S promoter completely or partially rescued Arabidopsis stt3a-2 mutant salt-sensitive phenotype, indicating STT3A functions conservatively between glycophyte and halophyte and N-glycosylation might be involved in plant resistance to salinity. 28510840 15 87 theme halophyte 2606:2614 arg1 tolerance 2593:2601 salt tolerance 2588:2601 salt tolerance of halophyte 2588:2614 Here we provided a first piece of evidence that the N-glycosylation might be involved in salt tolerance of halophyte. 28510840 11 88 theme 11 1755:1756 arg1 helices 1772:1778 13 and 11 transmembrane helices 1748:1778 helices 1772:1778 Subcellular localization and transmembrane structure prediction revealed that these two genes had 13 and 11 transmembrane helices respectively. 28510840 7 89 theme possible 1152:1159 arg1 roles 1172:1176 the possible biological roles 1148:1176 the possible biological roles of N-glycosylation in plant adaptive resistance to salinity stress 1148:1243 To explore the possible biological roles of N-glycosylation in plant adaptive resistance to salinity stress, we cloned the STT3 genes from S. alterniflora and heterogenously expressed them in Arabidopsis mutant to observe the functional conservation. 28510840 2 90 theme yeast 471:475 arg1 OST 477:479 the yeast OST 467:479 the yeast OST and in which Stt3p is proposed playing a central and conserved role in N-glycosylation 467:566 Biochemical and genetic assay leads to the identification of the nine subunits (Ost 1-6, Stt3, Swp1 and Wbp1) of the yeast OST and in which Stt3p is proposed playing a central and conserved role in N-glycosylation. 28510840 4 91 theme enzymatic 706:714 arg1 properties 716:725 different enzymatic properties 696:725 different enzymatic properties 696:725 OST with different catalytic STT3 isoforms has different enzymatic properties in mammals. 28510840 0 92 theme conserved 4:12 arg1 subunits 50:57 Two conserved oligosaccharyltransferase catalytic subunits 0:57 Two conserved oligosaccharyltransferase catalytic subunits required for N-glycosylation 0:86 Two conserved oligosaccharyltransferase catalytic subunits required for N-glycosylation exist in Spartina alterniflora. 28510840 5 93 theme protein 883:889 arg1 N-glycosylation 891:905 protein N-glycosylation 883:905 protein N-glycosylation 883:905 The mutation of STT3A in Arabidopsis thaliana causes a salt hypersensitive phenotype the inhibited root growth and swollen root tips suggesting protein N-glycosylation is indispensable for plant growth and development. 28510840 4 94 theme different 658:666 arg1 isoforms 683:690 different catalytic STT3 isoforms 658:690 different catalytic STT3 isoforms 658:690 OST with different catalytic STT3 isoforms has different enzymatic properties in mammals. 28510840 0 95 theme catalytic 40:48 arg1 subunits 50:57 Two conserved oligosaccharyltransferase catalytic subunits 0:57 Two conserved oligosaccharyltransferase catalytic subunits required for N-glycosylation 0:86 Two conserved oligosaccharyltransferase catalytic subunits required for N-glycosylation exist in Spartina alterniflora. 28510840 6 96 theme tidal 1024:1028 arg1 restoration 1036:1046 tidal marsh restoration 1024:1046 tidal marsh restoration 1024:1046 Spartina alterniflora is widely used for shoreline protection and tidal marsh restoration due to the strong salt tolerance although the exact molecular mechanism is little known. 28510840 11 97 theme transmembrane 1679:1691 arg1 prediction 1703:1712 transmembrane structure prediction 1679:1712 transmembrane structure prediction 1679:1712 Subcellular localization and transmembrane structure prediction revealed that these two genes had 13 and 11 transmembrane helices respectively. 28510840 7 98 gly N-glycosylation 1181:1195 arg1 plant 1200:1204 plant adaptive resistance 1200:1224 plant adaptive resistance to salinity stress 1200:1243 To explore the possible biological roles of N-glycosylation in plant adaptive resistance to salinity stress, we cloned the STT3 genes from S. alterniflora and heterogenously expressed them in Arabidopsis mutant to observe the functional conservation. 28510840 13 99 theme coding 2275:2280 arg1 sequences 2282:2290 coding sequences 2275:2290 coding sequences 2275:2290 CONCLUSIONS Two STT3 isoform genes, SaSTT3A and SaSTT3B, were cloned from S. alterniflora and they were evolutionally conserved at gene structure and coding sequences compared with their counterparts. 28510840 12 100 theme CaMV 1876:1879 arg1 promoter 1885:1892 CaMV 35S promoter 1876:1892 CaMV 35S promoter 1876:1892 The functional complementation in which the cDNA of SaSTT3A and SaSTT3B driven by CaMV 35S promoter completely or partially rescued Arabidopsis stt3a-2 mutant salt-sensitive phenotype, indicating STT3A functions conservatively between glycophyte and halophyte and N-glycosylation might be involved in plant resistance to salinity. 28510840 7 101 theme STT3 1260:1263 arg1 genes 1265:1269 the STT3 genes 1256:1269 the STT3 genes 1256:1269 To explore the possible biological roles of N-glycosylation in plant adaptive resistance to salinity stress, we cloned the STT3 genes from S. alterniflora and heterogenously expressed them in Arabidopsis mutant to observe the functional conservation. 28510840 15 102 gly N-glycosylation 2551:2565 arg1 tolerance 2593:2601 salt tolerance 2588:2601 salt tolerance of halophyte 2588:2614 Here we provided a first piece of evidence that the N-glycosylation might be involved in salt tolerance of halophyte. 28510840 10 103 theme plant 1635:1639 arg1 species 1641:1647 the analyzed plant species 1622:1647 the analyzed plant species 1622:1647 The gene structures of both genes were conserved among the analyzed plant species. 28510840 6 104 theme molecular 1100:1108 arg1 little 1123:1128 little 1123:1128 little 1123:1128 Spartina alterniflora is widely used for shoreline protection and tidal marsh restoration due to the strong salt tolerance although the exact molecular mechanism is little known. 28510840 6 104 theme molecular 1100:1108 arg1 mechanism 1110:1118 the exact molecular mechanism 1090:1118 the exact molecular mechanism 1090:1118 Spartina alterniflora is widely used for shoreline protection and tidal marsh restoration due to the strong salt tolerance although the exact molecular mechanism is little known. 28510840 7 105 theme salinity 1229:1236 arg1 stress 1238:1243 salinity stress 1229:1243 salinity stress 1229:1243 To explore the possible biological roles of N-glycosylation in plant adaptive resistance to salinity stress, we cloned the STT3 genes from S. alterniflora and heterogenously expressed them in Arabidopsis mutant to observe the functional conservation. 28510840 9 106 contain had 1540:1542 arg2 introns 1558:1564 5 introns 1556:1564 5 introns 1556:1564 SaSTT3A genomic sequences spanned over 23 exons and 22 introns, while SaSTT3B had 6 exons and 5 introns. 28510840 9 106 contain had 1540:1542 arg1 SaSTT3B 1532:1538 SaSTT3B 1532:1538 SaSTT3B 1532:1538 SaSTT3A genomic sequences spanned over 23 exons and 22 introns, while SaSTT3B had 6 exons and 5 introns. 28510840 9 106 contain had 1540:1542 arg2 exons 1546:1550 6 exons 1544:1550 6 exons 1544:1550 SaSTT3A genomic sequences spanned over 23 exons and 22 introns, while SaSTT3B had 6 exons and 5 introns. 28510840 2 107 theme genetic 370:376 arg1 assay 378:382 Biochemical and genetic assay 354:382 Biochemical and genetic assay 354:382 Biochemical and genetic assay leads to the identification of the nine subunits (Ost 1-6, Stt3, Swp1 and Wbp1) of the yeast OST and in which Stt3p is proposed playing a central and conserved role in N-glycosylation. 26306528 7 0 theme chGMII-GnMan5Gn 970:984 arg1 modes 961:965 the probable binding modes 940:965 the probable binding modes of chGMII-GnMan5Gn, chGMII-SW 940:995 By homology modeling and molecular docking, we obtained the predicted 3D structure of chGMII and the probable binding modes of chGMII-GnMan5Gn, chGMII-SW. 26306528 7 0 theme chGMII-GnMan5Gn 970:984 arg1 structure 916:924 the predicted 3D structure 899:924 the predicted 3D structure of chGMII 899:934 By homology modeling and molecular docking, we obtained the predicted 3D structure of chGMII and the probable binding modes of chGMII-GnMan5Gn, chGMII-SW. 26306528 1 1 theme glycosyl 119:126 arg1 α-mannosidase 88:100 Golgi α-mannosidase II 82:103 Golgi α-mannosidase II (GMII) 82:110 Golgi α-mannosidase II (GMII), a key glycosyl hydrolase in the N-linked glycosylation pathway, has been demonstrated to be closely associated with the genesis and development of cancer. 26306528 1 1 theme glycosyl 119:126 arg1 hydrolase 128:136 a key glycosyl hydrolase 113:136 a key glycosyl hydrolase in the N-linked glycosylation pathway 113:174 Golgi α-mannosidase II (GMII), a key glycosyl hydrolase in the N-linked glycosylation pathway, has been demonstrated to be closely associated with the genesis and development of cancer. 26306528 5 2 theme gene 577:580 arg1 profile 593:599 The gene expression profile 573:599 The gene expression profile analysis 573:608 The gene expression profile analysis showed GMII was the highest expressed gene in the spleen. 26306528 2 3 theme Capra 307:311 arg1 hircus 313:318 cDNA-encoding Capra hircus GMII 293:323 cDNA-encoding Capra hircus GMII (chGMII) 293:332 In this study, we cloned cDNA-encoding Capra hircus GMII (chGMII) and expressed it in Pichia pastoris expression system. 26306528 2 3 theme Capra 307:311 arg1 chGMII 326:331 chGMII 326:331 chGMII 326:331 In this study, we cloned cDNA-encoding Capra hircus GMII (chGMII) and expressed it in Pichia pastoris expression system. 26306528 5 4 from gene 648:651 arg1 spleen 660:665 the spleen 656:665 the spleen 656:665 The gene expression profile analysis showed GMII was the highest expressed gene in the spleen. 26306528 5 5 theme expression 582:591 arg1 profile 593:599 The gene expression profile 573:599 The gene expression profile analysis 573:608 The gene expression profile analysis showed GMII was the highest expressed gene in the spleen. 26306528 1 6 from hydrolase 128:136 arg1 pathway 168:174 the N-linked glycosylation pathway 141:174 the N-linked glycosylation pathway 141:174 Golgi α-mannosidase II (GMII), a key glycosyl hydrolase in the N-linked glycosylation pathway, has been demonstrated to be closely associated with the genesis and development of cancer. 26306528 3 7 theme amino 478:482 arg1 acids 484:488 1144 amino acids 473:488 1144 amino acids 473:488 The chGMII cDNA contains an open reading frame of 3432 bp encoding a polypeptide of 1144 amino acids. 26306528 3 8 theme acids 484:488 arg1 polypeptide 458:468 a polypeptide 456:468 a polypeptide of 1144 amino acids 456:488 The chGMII cDNA contains an open reading frame of 3432 bp encoding a polypeptide of 1144 amino acids. 26306528 3 9 theme 3432 bp 439:445 arg1 frame 430:434 an open reading frame 414:434 an open reading frame of 3432 bp encoding a polypeptide of 1144 amino acids 414:488 The chGMII cDNA contains an open reading frame of 3432 bp encoding a polypeptide of 1144 amino acids. 26306528 7 10 theme probable 944:951 arg1 modes 961:965 the probable binding modes 940:965 the probable binding modes of chGMII-GnMan5Gn, chGMII-SW 940:995 By homology modeling and molecular docking, we obtained the predicted 3D structure of chGMII and the probable binding modes of chGMII-GnMan5Gn, chGMII-SW. 26306528 1 11 link N-linked 145:152 arg1 pathway 168:174 the N-linked glycosylation pathway 141:174 the N-linked glycosylation pathway 141:174 Golgi α-mannosidase II (GMII), a key glycosyl hydrolase in the N-linked glycosylation pathway, has been demonstrated to be closely associated with the genesis and development of cancer. 26306528 8 12 theme small 1000:1004 arg1 cavity 1006:1011 A small cavity 998:1011 A small cavity containing Tyr355 and zinc ion fixed by residues Asp290, His176, Asp178, and His570 998:1095 A small cavity containing Tyr355 and zinc ion fixed by residues Asp290, His176, Asp178, and His570 was identified as the active center of chGMII. 26306528 8 12 theme small 1000:1004 arg1 center 1126:1131 the active center 1115:1131 the active center of chGMII 1115:1141 A small cavity containing Tyr355 and zinc ion fixed by residues Asp290, His176, Asp178, and His570 was identified as the active center of chGMII. 26306528 5 13 dep showed 610:615 arg1 gene 648:651 the highest expressed gene 626:651 the highest expressed gene in the spleen 626:665 The gene expression profile analysis showed GMII was the highest expressed gene in the spleen. 26306528 7 14 theme molecular 868:876 arg1 docking 878:884 molecular docking 868:884 molecular docking 868:884 By homology modeling and molecular docking, we obtained the predicted 3D structure of chGMII and the probable binding modes of chGMII-GnMan5Gn, chGMII-SW. 26306528 9 15 theme chGMII 1224:1229 arg1 mechanism 1211:1219 the catalytic mechanism 1197:1219 the catalytic mechanism of chGMII 1197:1229 These results not only provide a clue for clarifying the catalytic mechanism of chGMII but also lay a theoretical foundation for subsequent investigations in the field of anticancer therapy for mammals. 26306528 9 16 theme theoretical 1246:1256 arg1 foundation 1258:1267 a theoretical foundation 1244:1267 a theoretical foundation for subsequent investigations in the field of anticancer therapy for mammals 1244:1344 These results not only provide a clue for clarifying the catalytic mechanism of chGMII but also lay a theoretical foundation for subsequent investigations in the field of anticancer therapy for mammals. 26306528 4 17 theme deduced 495:501 arg1 mass 513:516 The deduced molecular mass 491:516 The deduced molecular mass 491:516 The deduced molecular mass and pI of chGMII was 130.5 kDa and 8.04, respectively. 26306528 4 17 theme deduced 495:501 arg1 130.5 kDa 539:547 130.5 kDa 539:547 130.5 kDa 539:547 The deduced molecular mass and pI of chGMII was 130.5 kDa and 8.04, respectively. 26306528 7 18 theme homology 846:853 arg1 modeling 855:862 homology modeling 846:862 homology modeling 846:862 By homology modeling and molecular docking, we obtained the predicted 3D structure of chGMII and the probable binding modes of chGMII-GnMan5Gn, chGMII-SW. 26306528 1 19 theme N-linked 145:152 arg1 pathway 168:174 the N-linked glycosylation pathway 141:174 the N-linked glycosylation pathway 141:174 Golgi α-mannosidase II (GMII), a key glycosyl hydrolase in the N-linked glycosylation pathway, has been demonstrated to be closely associated with the genesis and development of cancer. 26306528 1 20 theme Golgi 82:86 arg1 α-mannosidase 88:100 Golgi α-mannosidase II 82:103 Golgi α-mannosidase II (GMII) 82:110 Golgi α-mannosidase II (GMII), a key glycosyl hydrolase in the N-linked glycosylation pathway, has been demonstrated to be closely associated with the genesis and development of cancer. 26306528 1 20 theme Golgi 82:86 arg1 GMII 106:109 GMII 106:109 GMII 106:109 Golgi α-mannosidase II (GMII), a key glycosyl hydrolase in the N-linked glycosylation pathway, has been demonstrated to be closely associated with the genesis and development of cancer. 26306528 1 20 theme Golgi 82:86 arg1 hydrolase 128:136 a key glycosyl hydrolase 113:136 a key glycosyl hydrolase in the N-linked glycosylation pathway 113:174 Golgi α-mannosidase II (GMII), a key glycosyl hydrolase in the N-linked glycosylation pathway, has been demonstrated to be closely associated with the genesis and development of cancer. 26306528 0 21 dep α-Mannosidase 64:76 arg1 Expression 9:18 Expression 9:18 Expression 9:18 Cloning, Expression, and Characterization of Capra hircus Golgi α-Mannosidase II. 26306528 0 21 dep α-Mannosidase 64:76 arg1 Characterization 25:40 Characterization 25:40 Characterization 25:40 Cloning, Expression, and Characterization of Capra hircus Golgi α-Mannosidase II. 26306528 0 21 dep α-Mannosidase 64:76 arg1 Cloning 0:6 Cloning 0:6 Cloning 0:6 Cloning, Expression, and Characterization of Capra hircus Golgi α-Mannosidase II. 26306528 1 22 theme glycosylation 154:166 arg1 pathway 168:174 the N-linked glycosylation pathway 141:174 the N-linked glycosylation pathway 141:174 Golgi α-mannosidase II (GMII), a key glycosyl hydrolase in the N-linked glycosylation pathway, has been demonstrated to be closely associated with the genesis and development of cancer. 26306528 6 23 theme maximum 698:704 arg1 activity 706:713 maximum activity 698:713 maximum activity 698:713 The recombinant chGMII showed maximum activity at pH 5.4 and 42 °C and was activated by Fe(2+), Zn(2+), Ca(2+), and Mn(2+) and strongly inhibited by Co(2+), Cu(2+), and EDTA. 26306528 8 24 theme active 1119:1124 arg1 cavity 1006:1011 A small cavity 998:1011 A small cavity containing Tyr355 and zinc ion fixed by residues Asp290, His176, Asp178, and His570 998:1095 A small cavity containing Tyr355 and zinc ion fixed by residues Asp290, His176, Asp178, and His570 was identified as the active center of chGMII. 26306528 8 24 theme active 1119:1124 arg1 center 1126:1131 the active center 1115:1131 the active center of chGMII 1115:1141 A small cavity containing Tyr355 and zinc ion fixed by residues Asp290, His176, Asp178, and His570 was identified as the active center of chGMII. 26306528 2 25 theme pastoris 361:368 arg1 system 381:386 Pichia pastoris expression system 354:386 Pichia pastoris expression system 354:386 In this study, we cloned cDNA-encoding Capra hircus GMII (chGMII) and expressed it in Pichia pastoris expression system. 26306528 2 26 theme expression 370:379 arg1 system 381:386 Pichia pastoris expression system 354:386 Pichia pastoris expression system 354:386 In this study, we cloned cDNA-encoding Capra hircus GMII (chGMII) and expressed it in Pichia pastoris expression system. 26306528 4 27 theme molecular 503:511 arg1 mass 513:516 The deduced molecular mass 491:516 The deduced molecular mass 491:516 The deduced molecular mass and pI of chGMII was 130.5 kDa and 8.04, respectively. 26306528 4 27 theme molecular 503:511 arg1 130.5 kDa 539:547 130.5 kDa 539:547 130.5 kDa 539:547 The deduced molecular mass and pI of chGMII was 130.5 kDa and 8.04, respectively. 26306528 5 28 theme highest 630:636 arg1 gene 648:651 the highest expressed gene 626:651 the highest expressed gene in the spleen 626:665 The gene expression profile analysis showed GMII was the highest expressed gene in the spleen. 26306528 9 29 theme anticancer 1315:1324 arg1 therapy 1326:1332 anticancer therapy 1315:1332 anticancer therapy for mammals 1315:1344 These results not only provide a clue for clarifying the catalytic mechanism of chGMII but also lay a theoretical foundation for subsequent investigations in the field of anticancer therapy for mammals. 26306528 2 30 theme Pichia 354:359 arg1 pastoris 361:368 Pichia pastoris 354:368 Pichia pastoris expression system 354:386 In this study, we cloned cDNA-encoding Capra hircus GMII (chGMII) and expressed it in Pichia pastoris expression system. 26306528 7 31 theme 3D 913:914 arg1 structure 916:924 the predicted 3D structure 899:924 the predicted 3D structure of chGMII 899:934 By homology modeling and molecular docking, we obtained the predicted 3D structure of chGMII and the probable binding modes of chGMII-GnMan5Gn, chGMII-SW. 26306528 1 32 theme cancer 260:265 arg1 development 245:255 development 245:255 development 245:255 Golgi α-mannosidase II (GMII), a key glycosyl hydrolase in the N-linked glycosylation pathway, has been demonstrated to be closely associated with the genesis and development of cancer. 26306528 1 32 theme cancer 260:265 arg1 genesis 233:239 genesis 233:239 genesis 233:239 Golgi α-mannosidase II (GMII), a key glycosyl hydrolase in the N-linked glycosylation pathway, has been demonstrated to be closely associated with the genesis and development of cancer. 26306528 5 33 theme expressed 638:646 arg1 gene 648:651 the highest expressed gene 626:651 the highest expressed gene in the spleen 626:665 The gene expression profile analysis showed GMII was the highest expressed gene in the spleen. 26306528 9 34 theme catalytic 1201:1209 arg1 mechanism 1211:1219 the catalytic mechanism 1197:1219 the catalytic mechanism of chGMII 1197:1229 These results not only provide a clue for clarifying the catalytic mechanism of chGMII but also lay a theoretical foundation for subsequent investigations in the field of anticancer therapy for mammals. 26306528 9 35 theme therapy 1326:1332 arg1 field 1306:1310 the field 1302:1310 the field of anticancer therapy for mammals 1302:1344 These results not only provide a clue for clarifying the catalytic mechanism of chGMII but also lay a theoretical foundation for subsequent investigations in the field of anticancer therapy for mammals. 26306528 3 36 theme chGMII 393:398 arg1 cDNA 400:403 The chGMII cDNA 389:403 The chGMII cDNA 389:403 The chGMII cDNA contains an open reading frame of 3432 bp encoding a polypeptide of 1144 amino acids. 26306528 7 37 theme binding 953:959 arg1 modes 961:965 the probable binding modes 940:965 the probable binding modes of chGMII-GnMan5Gn, chGMII-SW 940:995 By homology modeling and molecular docking, we obtained the predicted 3D structure of chGMII and the probable binding modes of chGMII-GnMan5Gn, chGMII-SW. 26306528 0 38 theme Capra 45:49 arg1 hircus 51:56 Capra hircus 45:56 Capra hircus 45:56 Cloning, Expression, and Characterization of Capra hircus Golgi α-Mannosidase II. 26306528 3 39 contain contains 405:412 arg1 cDNA 400:403 The chGMII cDNA 389:403 The chGMII cDNA 389:403 The chGMII cDNA contains an open reading frame of 3432 bp encoding a polypeptide of 1144 amino acids. 26306528 3 39 contain contains 405:412 arg2 frame 430:434 an open reading frame 414:434 an open reading frame of 3432 bp encoding a polypeptide of 1144 amino acids 414:488 The chGMII cDNA contains an open reading frame of 3432 bp encoding a polypeptide of 1144 amino acids. 26306528 2 40 theme cDNA-encoding 293:305 arg1 hircus 313:318 cDNA-encoding Capra hircus GMII 293:323 cDNA-encoding Capra hircus GMII (chGMII) 293:332 In this study, we cloned cDNA-encoding Capra hircus GMII (chGMII) and expressed it in Pichia pastoris expression system. 26306528 2 40 theme cDNA-encoding 293:305 arg1 chGMII 326:331 chGMII 326:331 chGMII 326:331 In this study, we cloned cDNA-encoding Capra hircus GMII (chGMII) and expressed it in Pichia pastoris expression system. 26306528 7 41 theme predicted 903:911 arg1 structure 916:924 the predicted 3D structure 899:924 the predicted 3D structure of chGMII 899:934 By homology modeling and molecular docking, we obtained the predicted 3D structure of chGMII and the probable binding modes of chGMII-GnMan5Gn, chGMII-SW. 26306528 8 42 contain containing 1013:1022 arg1 cavity 1006:1011 A small cavity 998:1011 A small cavity containing Tyr355 and zinc ion fixed by residues Asp290, His176, Asp178, and His570 998:1095 A small cavity containing Tyr355 and zinc ion fixed by residues Asp290, His176, Asp178, and His570 was identified as the active center of chGMII. 26306528 8 42 contain containing 1013:1022 arg2 ion 1040:1042 zinc ion 1035:1042 zinc ion 1035:1042 A small cavity containing Tyr355 and zinc ion fixed by residues Asp290, His176, Asp178, and His570 was identified as the active center of chGMII. 26306528 8 42 contain containing 1013:1022 arg1 center 1126:1131 the active center 1115:1131 the active center of chGMII 1115:1141 A small cavity containing Tyr355 and zinc ion fixed by residues Asp290, His176, Asp178, and His570 was identified as the active center of chGMII. 26306528 8 42 contain containing 1013:1022 arg2 Tyr355 1024:1029 Tyr355 1024:1029 Tyr355 1024:1029 A small cavity containing Tyr355 and zinc ion fixed by residues Asp290, His176, Asp178, and His570 was identified as the active center of chGMII. 26306528 6 43 theme recombinant 672:682 arg1 chGMII 684:689 The recombinant chGMII 668:689 The recombinant chGMII 668:689 The recombinant chGMII showed maximum activity at pH 5.4 and 42 °C and was activated by Fe(2+), Zn(2+), Ca(2+), and Mn(2+) and strongly inhibited by Co(2+), Cu(2+), and EDTA. 26306528 8 44 theme fixed 1044:1048 arg1 Tyr355 1024:1029 Tyr355 1024:1029 Tyr355 1024:1029 A small cavity containing Tyr355 and zinc ion fixed by residues Asp290, His176, Asp178, and His570 was identified as the active center of chGMII. 26306528 9 45 theme subsequent 1273:1282 arg1 investigations 1284:1297 subsequent investigations 1273:1297 subsequent investigations in the field of anticancer therapy for mammals 1273:1344 These results not only provide a clue for clarifying the catalytic mechanism of chGMII but also lay a theoretical foundation for subsequent investigations in the field of anticancer therapy for mammals. 26306528 1 46 dep genesis 233:239 arg1 the 229:231 the 229:231 the 229:231 Golgi α-mannosidase II (GMII), a key glycosyl hydrolase in the N-linked glycosylation pathway, has been demonstrated to be closely associated with the genesis and development of cancer. 26306528 3 47 theme open 417:420 arg1 frame 430:434 an open reading frame 414:434 an open reading frame of 3432 bp encoding a polypeptide of 1144 amino acids 414:488 The chGMII cDNA contains an open reading frame of 3432 bp encoding a polypeptide of 1144 amino acids. 26306528 8 48 dep residues 1053:1060 arg1 His570 1090:1095 His570 1090:1095 His570 1090:1095 A small cavity containing Tyr355 and zinc ion fixed by residues Asp290, His176, Asp178, and His570 was identified as the active center of chGMII. 26306528 8 48 dep residues 1053:1060 arg1 His176 1070:1075 His176 1070:1075 His176 1070:1075 A small cavity containing Tyr355 and zinc ion fixed by residues Asp290, His176, Asp178, and His570 was identified as the active center of chGMII. 26306528 8 48 dep residues 1053:1060 arg1 Asp290 1062:1067 Asp290 1062:1067 Asp290 1062:1067 A small cavity containing Tyr355 and zinc ion fixed by residues Asp290, His176, Asp178, and His570 was identified as the active center of chGMII. 26306528 8 48 dep residues 1053:1060 arg1 residues 1053:1060 residues 1053:1060 residues Asp290, His176, Asp178, and His570 1053:1095 A small cavity containing Tyr355 and zinc ion fixed by residues Asp290, His176, Asp178, and His570 was identified as the active center of chGMII. 26306528 8 48 dep residues 1053:1060 arg1 Asp178 1078:1083 Asp178 1078:1083 Asp178 1078:1083 A small cavity containing Tyr355 and zinc ion fixed by residues Asp290, His176, Asp178, and His570 was identified as the active center of chGMII. 26306528 3 49 theme reading 422:428 arg1 frame 430:434 an open reading frame 414:434 an open reading frame of 3432 bp encoding a polypeptide of 1144 amino acids 414:488 The chGMII cDNA contains an open reading frame of 3432 bp encoding a polypeptide of 1144 amino acids. 26306528 4 50 theme chGMII 528:533 arg1 pI 522:523 pI 522:523 pI 522:523 The deduced molecular mass and pI of chGMII was 130.5 kDa and 8.04, respectively. 26306528 4 50 theme chGMII 528:533 arg1 mass 513:516 The deduced molecular mass 491:516 The deduced molecular mass 491:516 The deduced molecular mass and pI of chGMII was 130.5 kDa and 8.04, respectively. 26306528 4 50 theme chGMII 528:533 arg1 130.5 kDa 539:547 130.5 kDa 539:547 130.5 kDa 539:547 The deduced molecular mass and pI of chGMII was 130.5 kDa and 8.04, respectively. 26306528 0 51 theme Golgi 58:62 arg1 α-Mannosidase 64:76 Golgi α-Mannosidase II 58:79 Golgi α-Mannosidase II 58:79 Cloning, Expression, and Characterization of Capra hircus Golgi α-Mannosidase II. 26306528 8 52 theme zinc 1035:1038 arg1 ion 1040:1042 zinc ion 1035:1042 zinc ion 1035:1042 A small cavity containing Tyr355 and zinc ion fixed by residues Asp290, His176, Asp178, and His570 was identified as the active center of chGMII. 26306528 8 53 theme chGMII 1136:1141 arg1 cavity 1006:1011 A small cavity 998:1011 A small cavity containing Tyr355 and zinc ion fixed by residues Asp290, His176, Asp178, and His570 998:1095 A small cavity containing Tyr355 and zinc ion fixed by residues Asp290, His176, Asp178, and His570 was identified as the active center of chGMII. 26306528 8 53 theme chGMII 1136:1141 arg1 center 1126:1131 the active center 1115:1131 the active center of chGMII 1115:1141 A small cavity containing Tyr355 and zinc ion fixed by residues Asp290, His176, Asp178, and His570 was identified as the active center of chGMII. 26306528 5 54 theme profile 593:599 arg1 analysis 601:608 The gene expression profile analysis 573:608 The gene expression profile analysis 573:608 The gene expression profile analysis showed GMII was the highest expressed gene in the spleen. 26306528 0 55 theme hircus 51:56 arg1 Expression 9:18 Expression 9:18 Expression 9:18 Cloning, Expression, and Characterization of Capra hircus Golgi α-Mannosidase II. 26306528 0 55 theme hircus 51:56 arg1 Characterization 25:40 Characterization 25:40 Characterization 25:40 Cloning, Expression, and Characterization of Capra hircus Golgi α-Mannosidase II. 26306528 0 55 theme hircus 51:56 arg1 Cloning 0:6 Cloning 0:6 Cloning 0:6 Cloning, Expression, and Characterization of Capra hircus Golgi α-Mannosidase II. 26306528 7 56 theme chGMII 929:934 arg1 modes 961:965 the probable binding modes 940:965 the probable binding modes of chGMII-GnMan5Gn, chGMII-SW 940:995 By homology modeling and molecular docking, we obtained the predicted 3D structure of chGMII and the probable binding modes of chGMII-GnMan5Gn, chGMII-SW. 26306528 7 56 theme chGMII 929:934 arg1 structure 916:924 the predicted 3D structure 899:924 the predicted 3D structure of chGMII 899:934 By homology modeling and molecular docking, we obtained the predicted 3D structure of chGMII and the probable binding modes of chGMII-GnMan5Gn, chGMII-SW. 26306528 1 57 theme key 115:117 arg1 α-mannosidase 88:100 Golgi α-mannosidase II 82:103 Golgi α-mannosidase II (GMII) 82:110 Golgi α-mannosidase II (GMII), a key glycosyl hydrolase in the N-linked glycosylation pathway, has been demonstrated to be closely associated with the genesis and development of cancer. 26306528 1 57 theme key 115:117 arg1 hydrolase 128:136 a key glycosyl hydrolase 113:136 a key glycosyl hydrolase in the N-linked glycosylation pathway 113:174 Golgi α-mannosidase II (GMII), a key glycosyl hydrolase in the N-linked glycosylation pathway, has been demonstrated to be closely associated with the genesis and development of cancer. 26306528 9 58 from investigations 1284:1297 arg1 field 1306:1310 the field 1302:1310 the field of anticancer therapy for mammals 1302:1344 These results not only provide a clue for clarifying the catalytic mechanism of chGMII but also lay a theoretical foundation for subsequent investigations in the field of anticancer therapy for mammals. 25914713 7 0 theme LC-MS/MS 1091:1098 arg1 approaches 1100:1109 LC-MS/MS approaches 1091:1109 LC-MS/MS approaches 1091:1109 Although, being less sensitive than LC-MS/MS approaches in detecting and identifying low-abundant proteins, gel-based approaches are valuable tools for the differentiation and relative quantification of protein isoforms and/or modified proteins. 25914713 1 1 theme three-steps 128:138 arg1 procedure 151:159 a three-steps extraction procedure 126:159 a three-steps extraction procedure using sequentially CaCl2, EGTA, and LiCl-complemented buffers 126:221 Cell wall proteins were extracted from alfalfa stems according to a three-steps extraction procedure using sequentially CaCl2, EGTA, and LiCl-complemented buffers. 25914713 9 2 theme extracting 1484:1493 arg1 complementary 1599:1611 complementary 1599:1611 complementary 1599:1611 This study highlights how the extracting protocols as well as the analytical techniques devoted to the study of the plant cell wall proteome are complementary and how they may be combined to elucidate the dynamism of the plant cell wall proteome in biological studies. 25914713 9 2 theme extracting 1484:1493 arg1 protocols 1495:1503 the extracting protocols 1480:1503 the extracting protocols as well as the analytical techniques devoted to the study of the plant cell wall proteome 1480:1593 This study highlights how the extracting protocols as well as the analytical techniques devoted to the study of the plant cell wall proteome are complementary and how they may be combined to elucidate the dynamism of the plant cell wall proteome in biological studies. 25914713 1 3 theme extraction 140:149 arg1 procedure 151:159 a three-steps extraction procedure 126:159 a three-steps extraction procedure using sequentially CaCl2, EGTA, and LiCl-complemented buffers 126:221 Cell wall proteins were extracted from alfalfa stems according to a three-steps extraction procedure using sequentially CaCl2, EGTA, and LiCl-complemented buffers. 25914713 7 4 theme valuable 1188:1195 arg1 approaches 1173:1182 gel-based approaches 1163:1182 gel-based approaches 1163:1182 Although, being less sensitive than LC-MS/MS approaches in detecting and identifying low-abundant proteins, gel-based approaches are valuable tools for the differentiation and relative quantification of protein isoforms and/or modified proteins. 25914713 7 4 theme valuable 1188:1195 arg1 tools 1197:1201 valuable tools 1188:1201 valuable tools for the differentiation and relative quantification of protein isoforms and/or modified proteins 1188:1298 Although, being less sensitive than LC-MS/MS approaches in detecting and identifying low-abundant proteins, gel-based approaches are valuable tools for the differentiation and relative quantification of protein isoforms and/or modified proteins. 25914713 2 5 theme wall 276:279 arg1 proteins 281:288 cell wall proteins 271:288 cell wall proteins 271:288 The efficiency of this protocol for extracting cell wall proteins was compared with the two previously published methods optimized for alfalfa stem cell wall protein analysis. 25914713 8 6 theme N-linked 1398:1405 arg1 chains 1414:1419 different N-linked glycan chains 1388:1419 different N-linked glycan chains 1388:1419 In particular isoforms, having variations in their amino-acid sequence and/or carrying different N-linked glycan chains were detected and characterized. 25914713 8 7 theme different 1388:1396 arg1 chains 1414:1419 different N-linked glycan chains 1388:1419 different N-linked glycan chains 1388:1419 In particular isoforms, having variations in their amino-acid sequence and/or carrying different N-linked glycan chains were detected and characterized. 25914713 9 8 theme analytical 1520:1529 arg1 techniques 1531:1540 the analytical techniques 1516:1540 the extracting protocols as well as the analytical techniques devoted to the study of the plant cell wall proteome 1480:1593 This study highlights how the extracting protocols as well as the analytical techniques devoted to the study of the plant cell wall proteome are complementary and how they may be combined to elucidate the dynamism of the plant cell wall proteome in biological studies. 25914713 9 8 theme analytical 1520:1529 arg1 complementary 1599:1611 complementary 1599:1611 complementary 1599:1611 This study highlights how the extracting protocols as well as the analytical techniques devoted to the study of the plant cell wall proteome are complementary and how they may be combined to elucidate the dynamism of the plant cell wall proteome in biological studies. 25914713 2 9 theme cell 271:274 arg1 proteins 281:288 cell wall proteins 271:288 cell wall proteins 271:288 The efficiency of this protocol for extracting cell wall proteins was compared with the two previously published methods optimized for alfalfa stem cell wall protein analysis. 25914713 3 10 theme NCBInr 545:550 arg1 proteins 531:538 cell wall proteins 521:538 cell wall proteins (242 NCBInr identifiers) 521:563 Following LC-MS/MS analysis the three-steps extraction procedure resulted in the identification of the highest number of cell wall proteins (242 NCBInr identifiers) and gave the lowest percentage of non-cell wall proteins (about 30%). 25914713 3 10 theme NCBInr 545:550 arg1 identifiers 552:562 242 NCBInr identifiers 541:562 242 NCBInr identifiers 541:562 Following LC-MS/MS analysis the three-steps extraction procedure resulted in the identification of the highest number of cell wall proteins (242 NCBInr identifiers) and gave the lowest percentage of non-cell wall proteins (about 30%). 25914713 8 11 theme particular 1304:1313 arg1 isoforms 1315:1322 particular isoforms 1304:1322 particular isoforms 1304:1322 In particular isoforms, having variations in their amino-acid sequence and/or carrying different N-linked glycan chains were detected and characterized. 25914713 7 12 theme modified 1282:1289 arg1 proteins 1291:1298 modified proteins 1282:1298 modified proteins 1282:1298 Although, being less sensitive than LC-MS/MS approaches in detecting and identifying low-abundant proteins, gel-based approaches are valuable tools for the differentiation and relative quantification of protein isoforms and/or modified proteins. 25914713 9 13 theme cell 1681:1684 arg1 proteome 1691:1698 the plant cell wall proteome 1671:1698 the plant cell wall proteome 1671:1698 This study highlights how the extracting protocols as well as the analytical techniques devoted to the study of the plant cell wall proteome are complementary and how they may be combined to elucidate the dynamism of the plant cell wall proteome in biological studies. 25914713 3 14 theme proteins 531:538 arg1 number 511:516 the highest number 499:516 the highest number of cell wall proteins (242 NCBInr identifiers) 499:563 Following LC-MS/MS analysis the three-steps extraction procedure resulted in the identification of the highest number of cell wall proteins (242 NCBInr identifiers) and gave the lowest percentage of non-cell wall proteins (about 30%). 25914713 6 15 theme wall 1037:1040 arg1 compartment 1042:1052 the cell wall compartment 1028:1052 the cell wall compartment 1028:1052 With this technique, 75% of the identified proteins were shown to be fraction-specific and 72.7% were predicted as belonging to the cell wall compartment. 25914713 2 16 theme protein 382:388 arg1 analysis 390:397 wall protein analysis 377:397 stem cell wall protein analysis 367:397 The efficiency of this protocol for extracting cell wall proteins was compared with the two previously published methods optimized for alfalfa stem cell wall protein analysis. 25914713 9 17 theme wall 1686:1689 arg1 proteome 1691:1698 the plant cell wall proteome 1671:1698 the plant cell wall proteome 1671:1698 This study highlights how the extracting protocols as well as the analytical techniques devoted to the study of the plant cell wall proteome are complementary and how they may be combined to elucidate the dynamism of the plant cell wall proteome in biological studies. 25914713 1 18 theme Cell 60:63 arg1 proteins 70:77 Cell wall proteins 60:77 Cell wall proteins 60:77 Cell wall proteins were extracted from alfalfa stems according to a three-steps extraction procedure using sequentially CaCl2, EGTA, and LiCl-complemented buffers. 25914713 2 19 theme wall 377:380 arg1 analysis 390:397 wall protein analysis 377:397 stem cell wall protein analysis 367:397 The efficiency of this protocol for extracting cell wall proteins was compared with the two previously published methods optimized for alfalfa stem cell wall protein analysis. 25914713 0 20 theme improved 3:10 arg1 protocol 12:19 An improved protocol 0:19 An improved protocol 0:19 An improved protocol to study the plant cell wall proteome. 25914713 6 21 theme identified 932:941 arg1 proteins 943:950 the identified proteins 928:950 the identified proteins 928:950 With this technique, 75% of the identified proteins were shown to be fraction-specific and 72.7% were predicted as belonging to the cell wall compartment. 25914713 9 22 theme proteome 1691:1698 arg1 dynamism 1659:1666 the dynamism 1655:1666 the dynamism of the plant cell wall proteome in biological studies 1655:1720 This study highlights how the extracting protocols as well as the analytical techniques devoted to the study of the plant cell wall proteome are complementary and how they may be combined to elucidate the dynamism of the plant cell wall proteome in biological studies. 25914713 8 23 from variations 1332:1341 arg1 sequence 1363:1370 their amino-acid sequence 1346:1370 their amino-acid sequence 1346:1370 In particular isoforms, having variations in their amino-acid sequence and/or carrying different N-linked glycan chains were detected and characterized. 25914713 1 24 theme wall 65:68 arg1 proteins 70:77 Cell wall proteins 60:77 Cell wall proteins 60:77 Cell wall proteins were extracted from alfalfa stems according to a three-steps extraction procedure using sequentially CaCl2, EGTA, and LiCl-complemented buffers. 25914713 5 25 theme proteomic 843:851 arg1 characterization 853:868 a more detailed proteomic characterization 827:868 a more detailed proteomic characterization using 2D-gel electrophoresis 827:897 This three-step protocol was therefore selected for a more detailed proteomic characterization using 2D-gel electrophoresis. 25914713 5 26 theme three-step 780:789 arg1 protocol 791:798 This three-step protocol 775:798 This three-step protocol 775:798 This three-step protocol was therefore selected for a more detailed proteomic characterization using 2D-gel electrophoresis. 25914713 9 27 theme proteome 1586:1593 arg1 study 1557:1561 the study 1553:1561 the study of the plant cell wall proteome 1553:1593 This study highlights how the extracting protocols as well as the analytical techniques devoted to the study of the plant cell wall proteome are complementary and how they may be combined to elucidate the dynamism of the plant cell wall proteome in biological studies. 25914713 3 28 theme proteins 613:620 arg1 percentage 585:594 the lowest percentage 574:594 the lowest percentage of non-cell wall proteins 574:620 Following LC-MS/MS analysis the three-steps extraction procedure resulted in the identification of the highest number of cell wall proteins (242 NCBInr identifiers) and gave the lowest percentage of non-cell wall proteins (about 30%). 25914713 2 29 theme stem 367:370 arg1 cell 372:375 stem cell wall protein analysis 367:397 stem cell wall protein analysis 367:397 The efficiency of this protocol for extracting cell wall proteins was compared with the two previously published methods optimized for alfalfa stem cell wall protein analysis. 25914713 7 30 theme low-abundant 1140:1151 arg1 proteins 1153:1160 low-abundant proteins 1140:1160 low-abundant proteins 1140:1160 Although, being less sensitive than LC-MS/MS approaches in detecting and identifying low-abundant proteins, gel-based approaches are valuable tools for the differentiation and relative quantification of protein isoforms and/or modified proteins. 25914713 9 31 theme biological 1703:1712 arg1 studies 1714:1720 biological studies 1703:1720 biological studies 1703:1720 This study highlights how the extracting protocols as well as the analytical techniques devoted to the study of the plant cell wall proteome are complementary and how they may be combined to elucidate the dynamism of the plant cell wall proteome in biological studies. 25914713 8 32 theme glycan 1407:1412 arg1 chains 1414:1419 different N-linked glycan chains 1388:1419 different N-linked glycan chains 1388:1419 In particular isoforms, having variations in their amino-acid sequence and/or carrying different N-linked glycan chains were detected and characterized. 25914713 6 33 theme proteins 943:950 arg1 proteins 943:950 the identified proteins 928:950 the identified proteins 928:950 With this technique, 75% of the identified proteins were shown to be fraction-specific and 72.7% were predicted as belonging to the cell wall compartment. 25914713 6 33 theme proteins 943:950 arg1 % 923:923 75% 921:923 75% of the identified proteins 921:950 With this technique, 75% of the identified proteins were shown to be fraction-specific and 72.7% were predicted as belonging to the cell wall compartment. 25914713 9 34 theme cell 1576:1579 arg1 proteome 1586:1593 the plant cell wall proteome 1566:1593 the plant cell wall proteome 1566:1593 This study highlights how the extracting protocols as well as the analytical techniques devoted to the study of the plant cell wall proteome are complementary and how they may be combined to elucidate the dynamism of the plant cell wall proteome in biological studies. 25914713 3 35 dep gave 569:572 arg1 % 631:631 about 30% 623:631 about 30% 623:631 Following LC-MS/MS analysis the three-steps extraction procedure resulted in the identification of the highest number of cell wall proteins (242 NCBInr identifiers) and gave the lowest percentage of non-cell wall proteins (about 30%). 25914713 5 36 theme detailed 834:841 arg1 characterization 853:868 a more detailed proteomic characterization 827:868 a more detailed proteomic characterization using 2D-gel electrophoresis 827:897 This three-step protocol was therefore selected for a more detailed proteomic characterization using 2D-gel electrophoresis. 25914713 3 37 theme number 511:516 arg1 identification 481:494 the identification 477:494 the identification of the highest number of cell wall proteins (242 NCBInr identifiers) 477:563 Following LC-MS/MS analysis the three-steps extraction procedure resulted in the identification of the highest number of cell wall proteins (242 NCBInr identifiers) and gave the lowest percentage of non-cell wall proteins (about 30%). 25914713 3 38 theme highest 503:509 arg1 number 511:516 the highest number 499:516 the highest number of cell wall proteins (242 NCBInr identifiers) 499:563 Following LC-MS/MS analysis the three-steps extraction procedure resulted in the identification of the highest number of cell wall proteins (242 NCBInr identifiers) and gave the lowest percentage of non-cell wall proteins (about 30%). 25914713 7 39 dep differentiation 1211:1225 arg1 the 1207:1209 the 1207:1209 the 1207:1209 Although, being less sensitive than LC-MS/MS approaches in detecting and identifying low-abundant proteins, gel-based approaches are valuable tools for the differentiation and relative quantification of protein isoforms and/or modified proteins. 25914713 7 40 theme gel-based 1163:1171 arg1 approaches 1173:1182 gel-based approaches 1163:1182 gel-based approaches 1163:1182 Although, being less sensitive than LC-MS/MS approaches in detecting and identifying low-abundant proteins, gel-based approaches are valuable tools for the differentiation and relative quantification of protein isoforms and/or modified proteins. 25914713 7 40 theme gel-based 1163:1171 arg1 tools 1197:1201 valuable tools 1188:1201 valuable tools for the differentiation and relative quantification of protein isoforms and/or modified proteins 1188:1298 Although, being less sensitive than LC-MS/MS approaches in detecting and identifying low-abundant proteins, gel-based approaches are valuable tools for the differentiation and relative quantification of protein isoforms and/or modified proteins. 25914713 6 41 theme cell 1032:1035 arg1 compartment 1042:1052 the cell wall compartment 1028:1052 the cell wall compartment 1028:1052 With this technique, 75% of the identified proteins were shown to be fraction-specific and 72.7% were predicted as belonging to the cell wall compartment. 25914713 3 42 theme LC-MS/MS 410:417 arg1 analysis 419:426 LC-MS/MS analysis 410:426 LC-MS/MS analysis 410:426 Following LC-MS/MS analysis the three-steps extraction procedure resulted in the identification of the highest number of cell wall proteins (242 NCBInr identifiers) and gave the lowest percentage of non-cell wall proteins (about 30%). 25914713 4 43 theme identified 724:733 arg1 proteins 735:742 the identified proteins 720:742 the identified proteins 720:742 However, the three protocols are rather complementary than substitutive since 43% of the identified proteins were specific to one protocol. 25914713 0 44 theme cell 40:43 arg1 proteome 50:57 the plant cell wall proteome 30:57 the plant cell wall proteome 30:57 An improved protocol to study the plant cell wall proteome. 25914713 8 45 link N-linked 1398:1405 arg1 chains 1414:1419 different N-linked glycan chains 1388:1419 different N-linked glycan chains 1388:1419 In particular isoforms, having variations in their amino-acid sequence and/or carrying different N-linked glycan chains were detected and characterized. 25914713 8 46 theme amino-acid 1352:1361 arg1 sequence 1363:1370 their amino-acid sequence 1346:1370 their amino-acid sequence 1346:1370 In particular isoforms, having variations in their amino-acid sequence and/or carrying different N-linked glycan chains were detected and characterized. 25914713 3 47 theme three-steps 432:442 arg1 procedure 455:463 the three-steps extraction procedure 428:463 the three-steps extraction procedure 428:463 Following LC-MS/MS analysis the three-steps extraction procedure resulted in the identification of the highest number of cell wall proteins (242 NCBInr identifiers) and gave the lowest percentage of non-cell wall proteins (about 30%). 25914713 9 48 dep highlights 1465:1474 arg1 techniques 1531:1540 the analytical techniques 1516:1540 the extracting protocols as well as the analytical techniques devoted to the study of the plant cell wall proteome 1480:1593 This study highlights how the extracting protocols as well as the analytical techniques devoted to the study of the plant cell wall proteome are complementary and how they may be combined to elucidate the dynamism of the plant cell wall proteome in biological studies. 25914713 9 48 dep highlights 1465:1474 arg1 complementary 1599:1611 complementary 1599:1611 complementary 1599:1611 This study highlights how the extracting protocols as well as the analytical techniques devoted to the study of the plant cell wall proteome are complementary and how they may be combined to elucidate the dynamism of the plant cell wall proteome in biological studies. 25914713 9 48 dep highlights 1465:1474 arg1 protocols 1495:1503 the extracting protocols 1480:1503 the extracting protocols as well as the analytical techniques devoted to the study of the plant cell wall proteome 1480:1593 This study highlights how the extracting protocols as well as the analytical techniques devoted to the study of the plant cell wall proteome are complementary and how they may be combined to elucidate the dynamism of the plant cell wall proteome in biological studies. 25914713 9 48 dep highlights 1465:1474 arg1 combined 1633:1640 combined 1633:1640 may be combined to elucidate the dynamism of the plant cell wall proteome in biological studies 1626:1720 This study highlights how the extracting protocols as well as the analytical techniques devoted to the study of the plant cell wall proteome are complementary and how they may be combined to elucidate the dynamism of the plant cell wall proteome in biological studies. 25914713 2 49 theme published 327:335 arg1 methods 337:343 the two previously published methods 308:343 the two previously published methods optimized for alfalfa stem cell wall protein analysis 308:397 The efficiency of this protocol for extracting cell wall proteins was compared with the two previously published methods optimized for alfalfa stem cell wall protein analysis. 25914713 0 50 theme plant 34:38 arg1 proteome 50:57 the plant cell wall proteome 30:57 the plant cell wall proteome 30:57 An improved protocol to study the plant cell wall proteome. 25914713 9 51 from dynamism 1659:1666 arg1 studies 1714:1720 biological studies 1703:1720 biological studies 1703:1720 This study highlights how the extracting protocols as well as the analytical techniques devoted to the study of the plant cell wall proteome are complementary and how they may be combined to elucidate the dynamism of the plant cell wall proteome in biological studies. 25914713 3 52 theme lowest 578:583 arg1 percentage 585:594 the lowest percentage 574:594 the lowest percentage of non-cell wall proteins 574:620 Following LC-MS/MS analysis the three-steps extraction procedure resulted in the identification of the highest number of cell wall proteins (242 NCBInr identifiers) and gave the lowest percentage of non-cell wall proteins (about 30%). 25914713 9 53 theme plant 1675:1679 arg1 proteome 1691:1698 the plant cell wall proteome 1671:1698 the plant cell wall proteome 1671:1698 This study highlights how the extracting protocols as well as the analytical techniques devoted to the study of the plant cell wall proteome are complementary and how they may be combined to elucidate the dynamism of the plant cell wall proteome in biological studies. 25914713 1 54 theme alfalfa 99:105 arg1 stems 107:111 alfalfa stems 99:111 alfalfa stems 99:111 Cell wall proteins were extracted from alfalfa stems according to a three-steps extraction procedure using sequentially CaCl2, EGTA, and LiCl-complemented buffers. 25914713 7 55 theme protein 1258:1264 arg1 isoforms 1266:1273 protein isoforms 1258:1273 protein isoforms 1258:1273 Although, being less sensitive than LC-MS/MS approaches in detecting and identifying low-abundant proteins, gel-based approaches are valuable tools for the differentiation and relative quantification of protein isoforms and/or modified proteins. 25914713 2 56 theme protocol 247:254 arg1 efficiency 228:237 The efficiency 224:237 The efficiency of this protocol for extracting cell wall proteins 224:288 The efficiency of this protocol for extracting cell wall proteins was compared with the two previously published methods optimized for alfalfa stem cell wall protein analysis. 25914713 2 57 dep cell 372:375 arg1 analysis 390:397 wall protein analysis 377:397 stem cell wall protein analysis 367:397 The efficiency of this protocol for extracting cell wall proteins was compared with the two previously published methods optimized for alfalfa stem cell wall protein analysis. 25914713 10 58 with ProteomeXchange 1746:1760 arg1 identifier 1767:1776 identifier PXD001927 1767:1786 identifier PXD001927 1767:1786 Data are available via ProteomeXchange with identifier PXD001927. 25914713 7 59 theme isoforms 1266:1273 arg1 differentiation 1211:1225 differentiation 1211:1225 differentiation 1211:1225 Although, being less sensitive than LC-MS/MS approaches in detecting and identifying low-abundant proteins, gel-based approaches are valuable tools for the differentiation and relative quantification of protein isoforms and/or modified proteins. 25914713 7 59 theme isoforms 1266:1273 arg1 quantification 1240:1253 relative quantification 1231:1253 relative quantification 1231:1253 Although, being less sensitive than LC-MS/MS approaches in detecting and identifying low-abundant proteins, gel-based approaches are valuable tools for the differentiation and relative quantification of protein isoforms and/or modified proteins. 25914713 1 60 theme LiCl-complemented 197:213 arg1 buffers 215:221 LiCl-complemented buffers 197:221 LiCl-complemented buffers 197:221 Cell wall proteins were extracted from alfalfa stems according to a three-steps extraction procedure using sequentially CaCl2, EGTA, and LiCl-complemented buffers. 25914713 9 61 theme wall 1581:1584 arg1 proteome 1586:1593 the plant cell wall proteome 1566:1593 the plant cell wall proteome 1566:1593 This study highlights how the extracting protocols as well as the analytical techniques devoted to the study of the plant cell wall proteome are complementary and how they may be combined to elucidate the dynamism of the plant cell wall proteome in biological studies. 25914713 7 62 theme proteins 1291:1298 arg1 differentiation 1211:1225 differentiation 1211:1225 differentiation 1211:1225 Although, being less sensitive than LC-MS/MS approaches in detecting and identifying low-abundant proteins, gel-based approaches are valuable tools for the differentiation and relative quantification of protein isoforms and/or modified proteins. 25914713 7 62 theme proteins 1291:1298 arg1 quantification 1240:1253 relative quantification 1231:1253 relative quantification 1231:1253 Although, being less sensitive than LC-MS/MS approaches in detecting and identifying low-abundant proteins, gel-based approaches are valuable tools for the differentiation and relative quantification of protein isoforms and/or modified proteins. 25914713 4 63 theme proteins 735:742 arg1 proteins 735:742 the identified proteins 720:742 the identified proteins 720:742 However, the three protocols are rather complementary than substitutive since 43% of the identified proteins were specific to one protocol. 25914713 4 63 theme proteins 735:742 arg1 % 715:715 43% 713:715 43% of the identified proteins 713:742 However, the three protocols are rather complementary than substitutive since 43% of the identified proteins were specific to one protocol. 25914713 5 64 theme 2D-gel 876:881 arg1 electrophoresis 883:897 2D-gel electrophoresis 876:897 2D-gel electrophoresis 876:897 This three-step protocol was therefore selected for a more detailed proteomic characterization using 2D-gel electrophoresis. 25914713 3 65 theme non-cell 599:606 arg1 proteins 613:620 non-cell wall proteins 599:620 non-cell wall proteins 599:620 Following LC-MS/MS analysis the three-steps extraction procedure resulted in the identification of the highest number of cell wall proteins (242 NCBInr identifiers) and gave the lowest percentage of non-cell wall proteins (about 30%). 25914713 3 66 theme cell 521:524 arg1 proteins 531:538 cell wall proteins 521:538 cell wall proteins (242 NCBInr identifiers) 521:563 Following LC-MS/MS analysis the three-steps extraction procedure resulted in the identification of the highest number of cell wall proteins (242 NCBInr identifiers) and gave the lowest percentage of non-cell wall proteins (about 30%). 25914713 3 66 theme cell 521:524 arg1 identifiers 552:562 242 NCBInr identifiers 541:562 242 NCBInr identifiers 541:562 Following LC-MS/MS analysis the three-steps extraction procedure resulted in the identification of the highest number of cell wall proteins (242 NCBInr identifiers) and gave the lowest percentage of non-cell wall proteins (about 30%). 25914713 3 67 theme extraction 444:453 arg1 procedure 455:463 the three-steps extraction procedure 428:463 the three-steps extraction procedure 428:463 Following LC-MS/MS analysis the three-steps extraction procedure resulted in the identification of the highest number of cell wall proteins (242 NCBInr identifiers) and gave the lowest percentage of non-cell wall proteins (about 30%). 25914713 9 68 theme plant 1570:1574 arg1 proteome 1586:1593 the plant cell wall proteome 1566:1593 the plant cell wall proteome 1566:1593 This study highlights how the extracting protocols as well as the analytical techniques devoted to the study of the plant cell wall proteome are complementary and how they may be combined to elucidate the dynamism of the plant cell wall proteome in biological studies. 25914713 0 69 theme wall 45:48 arg1 proteome 50:57 the plant cell wall proteome 30:57 the plant cell wall proteome 30:57 An improved protocol to study the plant cell wall proteome. 25914713 3 70 theme wall 608:611 arg1 proteins 613:620 non-cell wall proteins 599:620 non-cell wall proteins 599:620 Following LC-MS/MS analysis the three-steps extraction procedure resulted in the identification of the highest number of cell wall proteins (242 NCBInr identifiers) and gave the lowest percentage of non-cell wall proteins (about 30%). 25914713 3 71 theme wall 526:529 arg1 proteins 531:538 cell wall proteins 521:538 cell wall proteins (242 NCBInr identifiers) 521:563 Following LC-MS/MS analysis the three-steps extraction procedure resulted in the identification of the highest number of cell wall proteins (242 NCBInr identifiers) and gave the lowest percentage of non-cell wall proteins (about 30%). 25914713 3 71 theme wall 526:529 arg1 identifiers 552:562 242 NCBInr identifiers 541:562 242 NCBInr identifiers 541:562 Following LC-MS/MS analysis the three-steps extraction procedure resulted in the identification of the highest number of cell wall proteins (242 NCBInr identifiers) and gave the lowest percentage of non-cell wall proteins (about 30%). 25914713 7 72 theme relative 1231:1238 arg1 quantification 1240:1253 relative quantification 1231:1253 relative quantification 1231:1253 Although, being less sensitive than LC-MS/MS approaches in detecting and identifying low-abundant proteins, gel-based approaches are valuable tools for the differentiation and relative quantification of protein isoforms and/or modified proteins. 25824284 2 0 theme death 373:377 arg1 induction 328:336 induction 328:336 induction of an inflammatory programmed cell death 328:377 For the leading human fungal pathogen Candida albicans, filamentation is thought to be required for immune cell escape via induction of an inflammatory programmed cell death. 25824284 4 1 theme C. 628:629 arg1 filamentation 640:652 C. albicans filamentation 628:652 C. albicans filamentation 628:652 We demonstrate that C. albicans filamentation is not required for escape from host immune cells; instead, macrophage pyroptosis is driven by fungal cell-wall remodelling and exposure of glycosylated proteins in response to the macrophage phagosome. 25824284 0 2 theme escape 69:74 arg1 mechanisms 45:54 mechanisms 45:54 mechanisms of host cell escape 45:74 Global analysis of fungal morphology exposes mechanisms of host cell escape. 25824284 5 3 dep killed 873:878 arg1 phagocytized 892:903 phagocytized 892:903 phagocytized 892:903 The capacity of killed, previously phagocytized cells to drive macrophage lysis is also observed with the distantly related fungal pathogen Cryptococcus neoformans. 25824284 1 4 theme diverse 179:185 arg1 pathogens 194:202 diverse fungal pathogens 179:202 diverse fungal pathogens 179:202 Developmental transitions between single-cell yeast and multicellular filaments underpin virulence of diverse fungal pathogens. 25824284 6 5 theme global 1044:1049 arg1 view 1051:1054 a global view 1042:1054 a global view of morphogenetic circuitry governing a key virulence trait 1042:1113 This study provides a global view of morphogenetic circuitry governing a key virulence trait, and illuminates a new mechanism by which fungi trigger host cell death. 25824284 2 6 theme cell 368:371 arg1 death 373:377 an inflammatory programmed cell death 341:377 an inflammatory programmed cell death 341:377 For the leading human fungal pathogen Candida albicans, filamentation is thought to be required for immune cell escape via induction of an inflammatory programmed cell death. 25824284 2 7 theme immune 305:310 arg1 escape 317:322 immune cell escape 305:322 immune cell escape 305:322 For the leading human fungal pathogen Candida albicans, filamentation is thought to be required for immune cell escape via induction of an inflammatory programmed cell death. 25824284 2 8 theme cell 312:315 arg1 escape 317:322 immune cell escape 305:322 immune cell escape 305:322 For the leading human fungal pathogen Candida albicans, filamentation is thought to be required for immune cell escape via induction of an inflammatory programmed cell death. 25824284 5 9 theme pathogen 988:995 arg1 neoformans 1010:1019 the distantly related fungal pathogen Cryptococcus neoformans 959:1019 the distantly related fungal pathogen Cryptococcus neoformans 959:1019 The capacity of killed, previously phagocytized cells to drive macrophage lysis is also observed with the distantly related fungal pathogen Cryptococcus neoformans. 25824284 4 10 theme proteins 807:814 arg1 exposure 782:789 exposure 782:789 exposure of glycosylated proteins 782:814 We demonstrate that C. albicans filamentation is not required for escape from host immune cells; instead, macrophage pyroptosis is driven by fungal cell-wall remodelling and exposure of glycosylated proteins in response to the macrophage phagosome. 25824284 4 10 theme proteins 807:814 arg1 remodelling 766:776 fungal cell-wall remodelling 749:776 fungal cell-wall remodelling 749:776 We demonstrate that C. albicans filamentation is not required for escape from host immune cells; instead, macrophage pyroptosis is driven by fungal cell-wall remodelling and exposure of glycosylated proteins in response to the macrophage phagosome. 25824284 3 11 theme N-linked 584:591 arg1 glycosylation 593:605 N-linked glycosylation 584:605 N-linked glycosylation 584:605 Here we perform a genome-scale analysis of C. albicans morphogenesis and identify 102 negative morphogenetic regulators and 872 positive regulators, highlighting key roles for ergosterol biosynthesis and N-linked glycosylation. 25824284 4 12 theme cell-wall 756:764 arg1 remodelling 766:776 fungal cell-wall remodelling 749:776 fungal cell-wall remodelling 749:776 We demonstrate that C. albicans filamentation is not required for escape from host immune cells; instead, macrophage pyroptosis is driven by fungal cell-wall remodelling and exposure of glycosylated proteins in response to the macrophage phagosome. 25824284 4 13 theme fungal 749:754 arg1 remodelling 766:776 fungal cell-wall remodelling 749:776 fungal cell-wall remodelling 749:776 We demonstrate that C. albicans filamentation is not required for escape from host immune cells; instead, macrophage pyroptosis is driven by fungal cell-wall remodelling and exposure of glycosylated proteins in response to the macrophage phagosome. 25824284 3 14 theme ergosterol 556:565 arg1 biosynthesis 567:578 ergosterol biosynthesis 556:578 ergosterol biosynthesis 556:578 Here we perform a genome-scale analysis of C. albicans morphogenesis and identify 102 negative morphogenetic regulators and 872 positive regulators, highlighting key roles for ergosterol biosynthesis and N-linked glycosylation. 25824284 5 15 theme macrophage 920:929 arg1 lysis 931:935 macrophage lysis 920:935 macrophage lysis 920:935 The capacity of killed, previously phagocytized cells to drive macrophage lysis is also observed with the distantly related fungal pathogen Cryptococcus neoformans. 25824284 1 16 theme fungal 187:192 arg1 pathogens 194:202 diverse fungal pathogens 179:202 diverse fungal pathogens 179:202 Developmental transitions between single-cell yeast and multicellular filaments underpin virulence of diverse fungal pathogens. 25824284 3 17 link N-linked 584:591 arg1 glycosylation 593:605 N-linked glycosylation 584:605 N-linked glycosylation 584:605 Here we perform a genome-scale analysis of C. albicans morphogenesis and identify 102 negative morphogenetic regulators and 872 positive regulators, highlighting key roles for ergosterol biosynthesis and N-linked glycosylation. 25824284 6 18 theme cell 1176:1179 arg1 death 1181:1185 host cell death 1171:1185 host cell death 1171:1185 This study provides a global view of morphogenetic circuitry governing a key virulence trait, and illuminates a new mechanism by which fungi trigger host cell death. 25824284 3 19 theme genome-scale 398:409 arg1 analysis 411:418 a genome-scale analysis 396:418 a genome-scale analysis of C. albicans morphogenesis 396:447 Here we perform a genome-scale analysis of C. albicans morphogenesis and identify 102 negative morphogenetic regulators and 872 positive regulators, highlighting key roles for ergosterol biosynthesis and N-linked glycosylation. 25824284 1 20 theme pathogens 194:202 arg1 virulence 166:174 virulence 166:174 virulence of diverse fungal pathogens 166:202 Developmental transitions between single-cell yeast and multicellular filaments underpin virulence of diverse fungal pathogens. 25824284 3 21 dep C. 423:424 arg1 albicans 426:433 albicans 426:433 albicans 426:433 Here we perform a genome-scale analysis of C. albicans morphogenesis and identify 102 negative morphogenetic regulators and 872 positive regulators, highlighting key roles for ergosterol biosynthesis and N-linked glycosylation. 25824284 1 22 theme Developmental 77:89 arg1 transitions 91:101 Developmental transitions 77:101 Developmental transitions between single-cell yeast and multicellular filaments 77:155 Developmental transitions between single-cell yeast and multicellular filaments underpin virulence of diverse fungal pathogens. 25824284 4 23 from cells 698:702 arg1 escape 674:679 escape 674:679 escape from host immune cells 674:702 We demonstrate that C. albicans filamentation is not required for escape from host immune cells; instead, macrophage pyroptosis is driven by fungal cell-wall remodelling and exposure of glycosylated proteins in response to the macrophage phagosome. 25824284 3 24 theme morphogenesis 435:447 arg1 analysis 411:418 a genome-scale analysis 396:418 a genome-scale analysis of C. albicans morphogenesis 396:447 Here we perform a genome-scale analysis of C. albicans morphogenesis and identify 102 negative morphogenetic regulators and 872 positive regulators, highlighting key roles for ergosterol biosynthesis and N-linked glycosylation. 25824284 0 25 theme Global 0:5 arg1 analysis 7:14 Global analysis 0:14 Global analysis of fungal morphology 0:35 Global analysis of fungal morphology exposes mechanisms of host cell escape. 25824284 4 26 from exposure 782:789 arg1 response 819:826 response 819:826 response to the macrophage phagosome 819:854 We demonstrate that C. albicans filamentation is not required for escape from host immune cells; instead, macrophage pyroptosis is driven by fungal cell-wall remodelling and exposure of glycosylated proteins in response to the macrophage phagosome. 25824284 5 27 theme Cryptococcus 997:1008 arg1 neoformans 1010:1019 the distantly related fungal pathogen Cryptococcus neoformans 959:1019 the distantly related fungal pathogen Cryptococcus neoformans 959:1019 The capacity of killed, previously phagocytized cells to drive macrophage lysis is also observed with the distantly related fungal pathogen Cryptococcus neoformans. 25824284 6 28 theme morphogenetic 1059:1071 arg1 circuitry 1073:1081 morphogenetic circuitry 1059:1081 morphogenetic circuitry governing a key virulence trait 1059:1113 This study provides a global view of morphogenetic circuitry governing a key virulence trait, and illuminates a new mechanism by which fungi trigger host cell death. 25824284 0 29 theme fungal 19:24 arg1 morphology 26:35 fungal morphology 19:35 fungal morphology 19:35 Global analysis of fungal morphology exposes mechanisms of host cell escape. 25824284 5 30 theme fungal 981:986 arg1 neoformans 1010:1019 the distantly related fungal pathogen Cryptococcus neoformans 959:1019 the distantly related fungal pathogen Cryptococcus neoformans 959:1019 The capacity of killed, previously phagocytized cells to drive macrophage lysis is also observed with the distantly related fungal pathogen Cryptococcus neoformans. 25824284 4 31 theme glycosylated 794:805 arg1 proteins 807:814 glycosylated proteins 794:814 glycosylated proteins 794:814 We demonstrate that C. albicans filamentation is not required for escape from host immune cells; instead, macrophage pyroptosis is driven by fungal cell-wall remodelling and exposure of glycosylated proteins in response to the macrophage phagosome. 25824284 5 32 theme killed 873:878 arg1 cells 905:909 killed, previously phagocytized cells 873:909 killed, previously phagocytized cells 873:909 The capacity of killed, previously phagocytized cells to drive macrophage lysis is also observed with the distantly related fungal pathogen Cryptococcus neoformans. 25824284 1 33 theme single-cell 111:121 arg1 yeast 123:127 single-cell yeast 111:127 single-cell yeast 111:127 Developmental transitions between single-cell yeast and multicellular filaments underpin virulence of diverse fungal pathogens. 25824284 3 34 theme C. 423:424 arg1 morphogenesis 435:447 C. albicans morphogenesis 423:447 C. albicans morphogenesis 423:447 Here we perform a genome-scale analysis of C. albicans morphogenesis and identify 102 negative morphogenetic regulators and 872 positive regulators, highlighting key roles for ergosterol biosynthesis and N-linked glycosylation. 25824284 4 35 theme immune 691:696 arg1 cells 698:702 host immune cells 686:702 host immune cells 686:702 We demonstrate that C. albicans filamentation is not required for escape from host immune cells; instead, macrophage pyroptosis is driven by fungal cell-wall remodelling and exposure of glycosylated proteins in response to the macrophage phagosome. 25824284 3 36 theme negative 466:473 arg1 regulators 489:498 102 negative morphogenetic regulators 462:498 102 negative morphogenetic regulators 462:498 Here we perform a genome-scale analysis of C. albicans morphogenesis and identify 102 negative morphogenetic regulators and 872 positive regulators, highlighting key roles for ergosterol biosynthesis and N-linked glycosylation. 25824284 0 37 theme morphology 26:35 arg1 analysis 7:14 Global analysis 0:14 Global analysis of fungal morphology 0:35 Global analysis of fungal morphology exposes mechanisms of host cell escape. 25824284 4 38 dep C. 628:629 arg1 albicans 631:638 albicans 631:638 albicans 631:638 We demonstrate that C. albicans filamentation is not required for escape from host immune cells; instead, macrophage pyroptosis is driven by fungal cell-wall remodelling and exposure of glycosylated proteins in response to the macrophage phagosome. 25824284 5 39 theme cells 905:909 arg1 capacity 861:868 The capacity 857:868 The capacity of killed, previously phagocytized cells to drive macrophage lysis 857:935 The capacity of killed, previously phagocytized cells to drive macrophage lysis is also observed with the distantly related fungal pathogen Cryptococcus neoformans. 25824284 3 40 theme morphogenetic 475:487 arg1 regulators 489:498 102 negative morphogenetic regulators 462:498 102 negative morphogenetic regulators 462:498 Here we perform a genome-scale analysis of C. albicans morphogenesis and identify 102 negative morphogenetic regulators and 872 positive regulators, highlighting key roles for ergosterol biosynthesis and N-linked glycosylation. 25824284 6 41 theme virulence 1099:1107 arg1 trait 1109:1113 a key virulence trait 1093:1113 a key virulence trait 1093:1113 This study provides a global view of morphogenetic circuitry governing a key virulence trait, and illuminates a new mechanism by which fungi trigger host cell death. 25824284 2 42 theme Candida 243:249 arg1 albicans 251:258 the leading human fungal pathogen Candida albicans 209:258 the leading human fungal pathogen Candida albicans 209:258 For the leading human fungal pathogen Candida albicans, filamentation is thought to be required for immune cell escape via induction of an inflammatory programmed cell death. 25824284 2 43 theme programmed 357:366 arg1 death 373:377 an inflammatory programmed cell death 341:377 an inflammatory programmed cell death 341:377 For the leading human fungal pathogen Candida albicans, filamentation is thought to be required for immune cell escape via induction of an inflammatory programmed cell death. 25824284 2 44 theme fungal 227:232 arg1 albicans 251:258 the leading human fungal pathogen Candida albicans 209:258 the leading human fungal pathogen Candida albicans 209:258 For the leading human fungal pathogen Candida albicans, filamentation is thought to be required for immune cell escape via induction of an inflammatory programmed cell death. 25824284 2 45 theme pathogen 234:241 arg1 albicans 251:258 the leading human fungal pathogen Candida albicans 209:258 the leading human fungal pathogen Candida albicans 209:258 For the leading human fungal pathogen Candida albicans, filamentation is thought to be required for immune cell escape via induction of an inflammatory programmed cell death. 25824284 3 46 theme key 542:544 arg1 roles 546:550 key roles 542:550 key roles 542:550 Here we perform a genome-scale analysis of C. albicans morphogenesis and identify 102 negative morphogenetic regulators and 872 positive regulators, highlighting key roles for ergosterol biosynthesis and N-linked glycosylation. 25824284 2 47 theme inflammatory 344:355 arg1 death 373:377 an inflammatory programmed cell death 341:377 an inflammatory programmed cell death 341:377 For the leading human fungal pathogen Candida albicans, filamentation is thought to be required for immune cell escape via induction of an inflammatory programmed cell death. 25824284 4 48 from remodelling 766:776 arg1 response 819:826 response 819:826 response to the macrophage phagosome 819:854 We demonstrate that C. albicans filamentation is not required for escape from host immune cells; instead, macrophage pyroptosis is driven by fungal cell-wall remodelling and exposure of glycosylated proteins in response to the macrophage phagosome. 25824284 2 49 theme human 221:225 arg1 albicans 251:258 the leading human fungal pathogen Candida albicans 209:258 the leading human fungal pathogen Candida albicans 209:258 For the leading human fungal pathogen Candida albicans, filamentation is thought to be required for immune cell escape via induction of an inflammatory programmed cell death. 25824284 4 50 theme macrophage 835:844 arg1 phagosome 846:854 the macrophage phagosome 831:854 the macrophage phagosome 831:854 We demonstrate that C. albicans filamentation is not required for escape from host immune cells; instead, macrophage pyroptosis is driven by fungal cell-wall remodelling and exposure of glycosylated proteins in response to the macrophage phagosome. 25824284 1 51 theme multicellular 133:145 arg1 filaments 147:155 multicellular filaments 133:155 multicellular filaments 133:155 Developmental transitions between single-cell yeast and multicellular filaments underpin virulence of diverse fungal pathogens. 25824284 6 52 theme host 1171:1174 arg1 death 1181:1185 host cell death 1171:1185 host cell death 1171:1185 This study provides a global view of morphogenetic circuitry governing a key virulence trait, and illuminates a new mechanism by which fungi trigger host cell death. 25824284 6 53 theme key 1095:1097 arg1 trait 1109:1113 a key virulence trait 1093:1113 a key virulence trait 1093:1113 This study provides a global view of morphogenetic circuitry governing a key virulence trait, and illuminates a new mechanism by which fungi trigger host cell death. 25824284 2 54 theme leading 213:219 arg1 albicans 251:258 the leading human fungal pathogen Candida albicans 209:258 the leading human fungal pathogen Candida albicans 209:258 For the leading human fungal pathogen Candida albicans, filamentation is thought to be required for immune cell escape via induction of an inflammatory programmed cell death. 25824284 3 55 theme positive 508:515 arg1 regulators 517:526 872 positive regulators 504:526 872 positive regulators 504:526 Here we perform a genome-scale analysis of C. albicans morphogenesis and identify 102 negative morphogenetic regulators and 872 positive regulators, highlighting key roles for ergosterol biosynthesis and N-linked glycosylation. 25824284 5 56 theme related 973:979 arg1 neoformans 1010:1019 the distantly related fungal pathogen Cryptococcus neoformans 959:1019 the distantly related fungal pathogen Cryptococcus neoformans 959:1019 The capacity of killed, previously phagocytized cells to drive macrophage lysis is also observed with the distantly related fungal pathogen Cryptococcus neoformans. 25824284 0 57 theme cell 64:67 arg1 escape 69:74 host cell escape 59:74 host cell escape 59:74 Global analysis of fungal morphology exposes mechanisms of host cell escape. 25824284 4 58 theme host 686:689 arg1 cells 698:702 host immune cells 686:702 host immune cells 686:702 We demonstrate that C. albicans filamentation is not required for escape from host immune cells; instead, macrophage pyroptosis is driven by fungal cell-wall remodelling and exposure of glycosylated proteins in response to the macrophage phagosome. 25824284 4 59 gly glycosylated 794:805 arg1 proteins 807:814 glycosylated proteins 794:814 glycosylated proteins 794:814 We demonstrate that C. albicans filamentation is not required for escape from host immune cells; instead, macrophage pyroptosis is driven by fungal cell-wall remodelling and exposure of glycosylated proteins in response to the macrophage phagosome. 25824284 6 60 theme new 1134:1136 arg1 mechanism 1138:1146 a new mechanism 1132:1146 a new mechanism by which fungi trigger host cell death 1132:1185 This study provides a global view of morphogenetic circuitry governing a key virulence trait, and illuminates a new mechanism by which fungi trigger host cell death. 25824284 0 61 theme host 59:62 arg1 escape 69:74 host cell escape 59:74 host cell escape 59:74 Global analysis of fungal morphology exposes mechanisms of host cell escape. 25824284 4 62 theme macrophage 714:723 arg1 pyroptosis 725:734 macrophage pyroptosis 714:734 macrophage pyroptosis 714:734 We demonstrate that C. albicans filamentation is not required for escape from host immune cells; instead, macrophage pyroptosis is driven by fungal cell-wall remodelling and exposure of glycosylated proteins in response to the macrophage phagosome. 25824284 6 63 theme circuitry 1073:1081 arg1 view 1051:1054 a global view 1042:1054 a global view of morphogenetic circuitry governing a key virulence trait 1042:1113 This study provides a global view of morphogenetic circuitry governing a key virulence trait, and illuminates a new mechanism by which fungi trigger host cell death. 25701360 3 0 theme amino 293:297 arg1 acids 299:303 amino acids metabolism 293:314 amino acids metabolism 293:314 It is the final product of amino acids metabolism, which contains sulfur-cysteine and homocysteine (Hcy). 25701360 4 1 theme protein-bound 448:460 arg1 Hcy 462:464 protein-bound Hcy 448:464 protein-bound Hcy (S-linked, and N-linked) 448:489 In human plasma, there are several various forms of homocysteine: free Hcy, protein-bound Hcy (S-linked, and N-linked), and homocysteine thiolactone (HTL). 25701360 4 1 theme protein-bound 448:460 arg1 forms 415:419 several various forms 399:419 several various forms of homocysteine: free Hcy, protein-bound Hcy (S-linked, and N-linked), and homocysteine thiolactone (HTL) 399:525 In human plasma, there are several various forms of homocysteine: free Hcy, protein-bound Hcy (S-linked, and N-linked), and homocysteine thiolactone (HTL). 25701360 5 2 theme blood 685:689 arg1 platelets 691:699 blood platelets 685:699 blood platelets 685:699 Our previous works have shown that both Hcy in the reduced form and its thiolactone may modify fibrinolysis, coagulation process, and biological activity of blood platelets. 25701360 6 3 theme superoxide 791:800 arg1 radicals 808:815 superoxide anion radicals 791:815 superoxide anion radicals (O 2 (-•) ) 791:827 Moreover, we have observed that HTL, like its precursor-Hcy stimulated the generation of superoxide anion radicals (O 2 (-•) ) in blood platelets. 25701360 3 4 theme acids 299:303 arg1 It 266:267 It 266:267 It 266:267 It is the final product of amino acids metabolism, which contains sulfur-cysteine and homocysteine (Hcy). 25701360 3 4 theme acids 299:303 arg1 product 282:288 the final product 272:288 the final product 272:288 It is the final product of amino acids metabolism, which contains sulfur-cysteine and homocysteine (Hcy). 25701360 7 5 theme tested 974:979 arg1 concentrations 981:994 tested concentrations 974:994 tested concentrations 974:994 The aim of our study in vitro was to establish the influence of sodium hydrosulfide (NaHS, as a fast-releasing H2S donor; at tested concentrations: 10-1000 µM) on the plasma lipid peroxidation induced by the reduced Hcy (at final concentrations of 0.01-1 mM) and HTL (at final concentrations of 0.1-1 µM). 25701360 7 6 theme final 1073:1077 arg1 concentrations 1079:1092 final concentrations 1073:1092 final concentrations of 0.01-1 mM 1073:1105 The aim of our study in vitro was to establish the influence of sodium hydrosulfide (NaHS, as a fast-releasing H2S donor; at tested concentrations: 10-1000 µM) on the plasma lipid peroxidation induced by the reduced Hcy (at final concentrations of 0.01-1 mM) and HTL (at final concentrations of 0.1-1 µM). 25701360 9 7 theme lipid 1388:1392 arg1 peroxidation 1394:1405 the lipid peroxidation 1384:1405 the lipid peroxidation in plasma preincubated with 1 mM Hcy or 1 µM HTL 1384:1454 The protective effect of 10 and 100 µM NaHS against the lipid peroxidation in plasma preincubated with 1 mM Hcy or 1 µM HTL was also observed. 25701360 7 8 theme 0.1-1 1144:1148 arg1 µM 1150:1151 0.1-1 µM 1144:1151 0.1-1 µM 1144:1151 The aim of our study in vitro was to establish the influence of sodium hydrosulfide (NaHS, as a fast-releasing H2S donor; at tested concentrations: 10-1000 µM) on the plasma lipid peroxidation induced by the reduced Hcy (at final concentrations of 0.01-1 mM) and HTL (at final concentrations of 0.1-1 µM). 25701360 5 9 theme reduced 579:585 arg1 form 587:590 the reduced form 575:590 the reduced form 575:590 Our previous works have shown that both Hcy in the reduced form and its thiolactone may modify fibrinolysis, coagulation process, and biological activity of blood platelets. 25701360 5 10 theme previous 532:539 arg1 works 541:545 Our previous works 528:545 Our previous works 528:545 Our previous works have shown that both Hcy in the reduced form and its thiolactone may modify fibrinolysis, coagulation process, and biological activity of blood platelets. 25701360 4 11 dep forms 415:419 arg1 Hcy 443:445 free Hcy 438:445 free Hcy 438:445 In human plasma, there are several various forms of homocysteine: free Hcy, protein-bound Hcy (S-linked, and N-linked), and homocysteine thiolactone (HTL). 25701360 4 11 dep forms 415:419 arg1 Hcy 462:464 protein-bound Hcy 448:464 protein-bound Hcy (S-linked, and N-linked) 448:489 In human plasma, there are several various forms of homocysteine: free Hcy, protein-bound Hcy (S-linked, and N-linked), and homocysteine thiolactone (HTL). 25701360 4 11 dep forms 415:419 arg1 HTL 522:524 HTL 522:524 HTL 522:524 In human plasma, there are several various forms of homocysteine: free Hcy, protein-bound Hcy (S-linked, and N-linked), and homocysteine thiolactone (HTL). 25701360 4 11 dep forms 415:419 arg1 forms 415:419 several various forms 399:419 several various forms of homocysteine: free Hcy, protein-bound Hcy (S-linked, and N-linked), and homocysteine thiolactone (HTL) 399:525 In human plasma, there are several various forms of homocysteine: free Hcy, protein-bound Hcy (S-linked, and N-linked), and homocysteine thiolactone (HTL). 25701360 4 11 dep forms 415:419 arg1 thiolactone 509:519 homocysteine thiolactone 496:519 homocysteine thiolactone (HTL) 496:525 In human plasma, there are several various forms of homocysteine: free Hcy, protein-bound Hcy (S-linked, and N-linked), and homocysteine thiolactone (HTL). 25701360 7 12 from concentrations 1126:1139 arg1 HTL 1112:1114 HTL 1112:1114 HTL (at final concentrations of 0.1-1 µM) 1112:1152 The aim of our study in vitro was to establish the influence of sodium hydrosulfide (NaHS, as a fast-releasing H2S donor; at tested concentrations: 10-1000 µM) on the plasma lipid peroxidation induced by the reduced Hcy (at final concentrations of 0.01-1 mM) and HTL (at final concentrations of 0.1-1 µM). 25701360 7 12 from concentrations 1126:1139 arg1 Hcy 1065:1067 the reduced Hcy 1053:1067 the reduced Hcy (at final concentrations of 0.01-1 mM) 1053:1106 The aim of our study in vitro was to establish the influence of sodium hydrosulfide (NaHS, as a fast-releasing H2S donor; at tested concentrations: 10-1000 µM) on the plasma lipid peroxidation induced by the reduced Hcy (at final concentrations of 0.01-1 mM) and HTL (at final concentrations of 0.1-1 µM). 25701360 4 13 theme free 438:441 arg1 Hcy 443:445 free Hcy 438:445 free Hcy 438:445 In human plasma, there are several various forms of homocysteine: free Hcy, protein-bound Hcy (S-linked, and N-linked), and homocysteine thiolactone (HTL). 25701360 4 13 theme free 438:441 arg1 forms 415:419 several various forms 399:419 several various forms of homocysteine: free Hcy, protein-bound Hcy (S-linked, and N-linked), and homocysteine thiolactone (HTL) 399:525 In human plasma, there are several various forms of homocysteine: free Hcy, protein-bound Hcy (S-linked, and N-linked), and homocysteine thiolactone (HTL). 25701360 7 14 from concentrations 1079:1092 arg1 HTL 1112:1114 HTL 1112:1114 HTL (at final concentrations of 0.1-1 µM) 1112:1152 The aim of our study in vitro was to establish the influence of sodium hydrosulfide (NaHS, as a fast-releasing H2S donor; at tested concentrations: 10-1000 µM) on the plasma lipid peroxidation induced by the reduced Hcy (at final concentrations of 0.01-1 mM) and HTL (at final concentrations of 0.1-1 µM). 25701360 7 14 from concentrations 1079:1092 arg1 Hcy 1065:1067 the reduced Hcy 1053:1067 the reduced Hcy (at final concentrations of 0.01-1 mM) 1053:1106 The aim of our study in vitro was to establish the influence of sodium hydrosulfide (NaHS, as a fast-releasing H2S donor; at tested concentrations: 10-1000 µM) on the plasma lipid peroxidation induced by the reduced Hcy (at final concentrations of 0.01-1 mM) and HTL (at final concentrations of 0.1-1 µM). 25701360 7 15 dep NaHS 934:937 arg1 µM 1005:1006 10-1000 µM 997:1006 10-1000 µM 997:1006 The aim of our study in vitro was to establish the influence of sodium hydrosulfide (NaHS, as a fast-releasing H2S donor; at tested concentrations: 10-1000 µM) on the plasma lipid peroxidation induced by the reduced Hcy (at final concentrations of 0.01-1 mM) and HTL (at final concentrations of 0.1-1 µM). 25701360 7 16 theme lipid 1023:1027 arg1 peroxidation 1029:1040 the plasma lipid peroxidation 1012:1040 the plasma lipid peroxidation induced by the reduced Hcy (at final concentrations of 0.01-1 mM) and HTL (at final concentrations of 0.1-1 µM) 1012:1152 The aim of our study in vitro was to establish the influence of sodium hydrosulfide (NaHS, as a fast-releasing H2S donor; at tested concentrations: 10-1000 µM) on the plasma lipid peroxidation induced by the reduced Hcy (at final concentrations of 0.01-1 mM) and HTL (at final concentrations of 0.1-1 µM). 25701360 6 17 theme radicals 808:815 arg1 generation 777:786 the generation 773:786 the generation of superoxide anion radicals (O 2 (-•) ) in blood platelets 773:846 Moreover, we have observed that HTL, like its precursor-Hcy stimulated the generation of superoxide anion radicals (O 2 (-•) ) in blood platelets. 25701360 7 18 theme fast-releasing 945:958 arg1 donor 964:968 a fast-releasing H2S donor; 943:969 a fast-releasing H2S donor; at tested concentrations 943:994 The aim of our study in vitro was to establish the influence of sodium hydrosulfide (NaHS, as a fast-releasing H2S donor; at tested concentrations: 10-1000 µM) on the plasma lipid peroxidation induced by the reduced Hcy (at final concentrations of 0.01-1 mM) and HTL (at final concentrations of 0.1-1 µM). 25701360 4 19 theme human 375:379 arg1 plasma 381:386 human plasma 375:386 human plasma 375:386 In human plasma, there are several various forms of homocysteine: free Hcy, protein-bound Hcy (S-linked, and N-linked), and homocysteine thiolactone (HTL). 25701360 1 20 theme recent 157:162 arg1 years 164:168 recent years 157:168 recent years 157:168 Hydrogen sulfide (H2S) has been investigated widely in recent years. 25701360 5 21 theme biological 662:671 arg1 activity 673:680 biological activity 662:680 biological activity of blood platelets 662:699 Our previous works have shown that both Hcy in the reduced form and its thiolactone may modify fibrinolysis, coagulation process, and biological activity of blood platelets. 25701360 6 22 theme anion 802:806 arg1 radicals 808:815 superoxide anion radicals 791:815 superoxide anion radicals (O 2 (-•) ) 791:827 Moreover, we have observed that HTL, like its precursor-Hcy stimulated the generation of superoxide anion radicals (O 2 (-•) ) in blood platelets. 25701360 7 23 theme H2S 960:962 arg1 donor 964:968 a fast-releasing H2S donor; 943:969 a fast-releasing H2S donor; at tested concentrations 943:994 The aim of our study in vitro was to establish the influence of sodium hydrosulfide (NaHS, as a fast-releasing H2S donor; at tested concentrations: 10-1000 µM) on the plasma lipid peroxidation induced by the reduced Hcy (at final concentrations of 0.01-1 mM) and HTL (at final concentrations of 0.1-1 µM). 25701360 7 24 theme plasma 1016:1021 arg1 peroxidation 1029:1040 the plasma lipid peroxidation 1012:1040 the plasma lipid peroxidation induced by the reduced Hcy (at final concentrations of 0.01-1 mM) and HTL (at final concentrations of 0.1-1 µM) 1012:1152 The aim of our study in vitro was to establish the influence of sodium hydrosulfide (NaHS, as a fast-releasing H2S donor; at tested concentrations: 10-1000 µM) on the plasma lipid peroxidation induced by the reduced Hcy (at final concentrations of 0.01-1 mM) and HTL (at final concentrations of 0.1-1 µM). 25701360 8 25 theme mM 1258:1259 arg1 Hcy 1261:1263 1 mM Hcy 1256:1263 1 mM Hcy 1256:1263 Our results indicate that 10 and 100 µM NaHS decreased the lipid peroxidation in plasma treated with 1 mM Hcy or 1 µM HTL (when NaHS and Hcy/HTL were added to plasma together). 25701360 7 26 theme µM 1150:1151 arg1 concentrations 1126:1139 final concentrations 1120:1139 final concentrations of 0.1-1 µM 1120:1151 The aim of our study in vitro was to establish the influence of sodium hydrosulfide (NaHS, as a fast-releasing H2S donor; at tested concentrations: 10-1000 µM) on the plasma lipid peroxidation induced by the reduced Hcy (at final concentrations of 0.01-1 mM) and HTL (at final concentrations of 0.1-1 µM). 25701360 10 27 theme homocysteine 1591:1602 arg1 forms 1582:1586 different forms 1572:1586 different forms of homocysteine 1572:1602 Considering the data presented in this study, we suggest that the lipid peroxidation (induced by different forms of homocysteine) may be reduced by hydrogen sulfide. 25701360 5 28 theme platelets 691:699 arg1 fibrinolysis 623:634 fibrinolysis 623:634 fibrinolysis 623:634 Our previous works have shown that both Hcy in the reduced form and its thiolactone may modify fibrinolysis, coagulation process, and biological activity of blood platelets. 25701360 5 28 theme platelets 691:699 arg1 process 649:655 coagulation process 637:655 coagulation process 637:655 Our previous works have shown that both Hcy in the reduced form and its thiolactone may modify fibrinolysis, coagulation process, and biological activity of blood platelets. 25701360 5 28 theme platelets 691:699 arg1 activity 673:680 biological activity 662:680 biological activity of blood platelets 662:699 Our previous works have shown that both Hcy in the reduced form and its thiolactone may modify fibrinolysis, coagulation process, and biological activity of blood platelets. 25701360 7 29 theme reduced 1057:1063 arg1 Hcy 1065:1067 the reduced Hcy 1053:1067 the reduced Hcy (at final concentrations of 0.01-1 mM) 1053:1106 The aim of our study in vitro was to establish the influence of sodium hydrosulfide (NaHS, as a fast-releasing H2S donor; at tested concentrations: 10-1000 µM) on the plasma lipid peroxidation induced by the reduced Hcy (at final concentrations of 0.01-1 mM) and HTL (at final concentrations of 0.1-1 µM). 25701360 0 30 theme Hydrogen 0:7 arg1 sulfide 9:15 Hydrogen sulfide 0:15 Hydrogen sulfide 0:15 Hydrogen sulfide decreases the plasma lipid peroxidation induced by homocysteine and its thiolactone. 25701360 9 31 theme 1 1435:1435 arg1 mM 1437:1438 mM 1437:1438 mM 1437:1438 The protective effect of 10 and 100 µM NaHS against the lipid peroxidation in plasma preincubated with 1 mM Hcy or 1 µM HTL was also observed. 25701360 8 32 from peroxidation 1220:1231 arg1 plasma 1236:1241 plasma 1236:1241 plasma treated with 1 mM Hcy or 1 µM HTL (when NaHS and Hcy/HTL were added to plasma together) 1236:1329 Our results indicate that 10 and 100 µM NaHS decreased the lipid peroxidation in plasma treated with 1 mM Hcy or 1 µM HTL (when NaHS and Hcy/HTL were added to plasma together). 25701360 5 33 from Hcy 568:570 arg1 form 587:590 the reduced form 575:590 the reduced form 575:590 Our previous works have shown that both Hcy in the reduced form and its thiolactone may modify fibrinolysis, coagulation process, and biological activity of blood platelets. 25701360 9 34 theme mM 1437:1438 arg1 Hcy 1440:1442 1 mM Hcy or 1 µM HTL 1435:1454 Hcy 1440:1442 The protective effect of 10 and 100 µM NaHS against the lipid peroxidation in plasma preincubated with 1 mM Hcy or 1 µM HTL was also observed. 25701360 1 35 theme Hydrogen 102:109 arg1 H2S 120:122 H2S 120:122 H2S 120:122 Hydrogen sulfide (H2S) has been investigated widely in recent years. 25701360 1 35 theme Hydrogen 102:109 arg1 sulfide 111:117 Hydrogen sulfide 102:117 Hydrogen sulfide (H2S) 102:123 Hydrogen sulfide (H2S) has been investigated widely in recent years. 25701360 8 36 theme µM 1192:1193 arg1 NaHS 1195:1198 10 and 100 µM NaHS 1181:1198 10 and 100 µM NaHS 1181:1198 Our results indicate that 10 and 100 µM NaHS decreased the lipid peroxidation in plasma treated with 1 mM Hcy or 1 µM HTL (when NaHS and Hcy/HTL were added to plasma together). 25701360 6 37 from generation 777:786 arg1 platelets 838:846 blood platelets 832:846 blood platelets 832:846 Moreover, we have observed that HTL, like its precursor-Hcy stimulated the generation of superoxide anion radicals (O 2 (-•) ) in blood platelets. 25701360 3 38 dep acids 299:303 arg1 metabolism 305:314 metabolism 305:314 amino acids metabolism 293:314 It is the final product of amino acids metabolism, which contains sulfur-cysteine and homocysteine (Hcy). 25701360 10 39 theme different 1572:1580 arg1 forms 1582:1586 different forms 1572:1586 different forms of homocysteine 1572:1602 Considering the data presented in this study, we suggest that the lipid peroxidation (induced by different forms of homocysteine) may be reduced by hydrogen sulfide. 25701360 9 40 theme protective 1336:1345 arg1 effect 1347:1352 The protective effect 1332:1352 The protective effect of 10 and 100 µM NaHS against the lipid peroxidation in plasma preincubated with 1 mM Hcy or 1 µM HTL 1332:1454 The protective effect of 10 and 100 µM NaHS against the lipid peroxidation in plasma preincubated with 1 mM Hcy or 1 µM HTL was also observed. 25701360 7 41 theme final 1120:1124 arg1 concentrations 1126:1139 final concentrations 1120:1139 final concentrations of 0.1-1 µM 1120:1151 The aim of our study in vitro was to establish the influence of sodium hydrosulfide (NaHS, as a fast-releasing H2S donor; at tested concentrations: 10-1000 µM) on the plasma lipid peroxidation induced by the reduced Hcy (at final concentrations of 0.01-1 mM) and HTL (at final concentrations of 0.1-1 µM). 25701360 0 42 theme lipid 38:42 arg1 peroxidation 44:55 the plasma lipid peroxidation 27:55 the plasma lipid peroxidation induced by homocysteine and its thiolactone 27:99 Hydrogen sulfide decreases the plasma lipid peroxidation induced by homocysteine and its thiolactone. 25701360 4 43 theme homocysteine 496:507 arg1 forms 415:419 several various forms 399:419 several various forms of homocysteine: free Hcy, protein-bound Hcy (S-linked, and N-linked), and homocysteine thiolactone (HTL) 399:525 In human plasma, there are several various forms of homocysteine: free Hcy, protein-bound Hcy (S-linked, and N-linked), and homocysteine thiolactone (HTL). 25701360 4 43 theme homocysteine 496:507 arg1 HTL 522:524 HTL 522:524 HTL 522:524 In human plasma, there are several various forms of homocysteine: free Hcy, protein-bound Hcy (S-linked, and N-linked), and homocysteine thiolactone (HTL). 25701360 4 43 theme homocysteine 496:507 arg1 thiolactone 509:519 homocysteine thiolactone 496:519 homocysteine thiolactone (HTL) 496:525 In human plasma, there are several various forms of homocysteine: free Hcy, protein-bound Hcy (S-linked, and N-linked), and homocysteine thiolactone (HTL). 25701360 7 44 theme hydrosulfide 920:931 arg1 influence 900:908 the influence 896:908 the influence of sodium hydrosulfide (NaHS, as a fast-releasing H2S donor; at tested concentrations: 10-1000 µM) on the plasma lipid peroxidation induced by the reduced Hcy (at final concentrations of 0.01-1 mM) and HTL (at final concentrations of 0.1-1 µM) 896:1152 The aim of our study in vitro was to establish the influence of sodium hydrosulfide (NaHS, as a fast-releasing H2S donor; at tested concentrations: 10-1000 µM) on the plasma lipid peroxidation induced by the reduced Hcy (at final concentrations of 0.01-1 mM) and HTL (at final concentrations of 0.1-1 µM). 25701360 4 45 theme various 407:413 arg1 Hcy 443:445 free Hcy 438:445 free Hcy 438:445 In human plasma, there are several various forms of homocysteine: free Hcy, protein-bound Hcy (S-linked, and N-linked), and homocysteine thiolactone (HTL). 25701360 4 45 theme various 407:413 arg1 forms 415:419 several various forms 399:419 several various forms of homocysteine: free Hcy, protein-bound Hcy (S-linked, and N-linked), and homocysteine thiolactone (HTL) 399:525 In human plasma, there are several various forms of homocysteine: free Hcy, protein-bound Hcy (S-linked, and N-linked), and homocysteine thiolactone (HTL). 25701360 4 45 theme various 407:413 arg1 thiolactone 509:519 homocysteine thiolactone 496:519 homocysteine thiolactone (HTL) 496:525 In human plasma, there are several various forms of homocysteine: free Hcy, protein-bound Hcy (S-linked, and N-linked), and homocysteine thiolactone (HTL). 25701360 4 45 theme various 407:413 arg1 Hcy 462:464 protein-bound Hcy 448:464 protein-bound Hcy (S-linked, and N-linked) 448:489 In human plasma, there are several various forms of homocysteine: free Hcy, protein-bound Hcy (S-linked, and N-linked), and homocysteine thiolactone (HTL). 25701360 2 46 theme biological 213:222 arg1 system 258:263 cardiovascular system 243:263 cardiovascular system 243:263 H2S plays a variety of roles in different biological systems, including cardiovascular system. 25701360 2 46 theme biological 213:222 arg1 systems 224:230 different biological systems 203:230 different biological systems 203:230 H2S plays a variety of roles in different biological systems, including cardiovascular system. 25701360 0 47 theme plasma 31:36 arg1 peroxidation 44:55 the plasma lipid peroxidation 27:55 the plasma lipid peroxidation induced by homocysteine and its thiolactone 27:99 Hydrogen sulfide decreases the plasma lipid peroxidation induced by homocysteine and its thiolactone. 25701360 6 48 theme blood 832:836 arg1 platelets 838:846 blood platelets 832:846 blood platelets 832:846 Moreover, we have observed that HTL, like its precursor-Hcy stimulated the generation of superoxide anion radicals (O 2 (-•) ) in blood platelets. 25701360 5 49 theme coagulation 637:647 arg1 process 649:655 coagulation process 637:655 coagulation process 637:655 Our previous works have shown that both Hcy in the reduced form and its thiolactone may modify fibrinolysis, coagulation process, and biological activity of blood platelets. 25701360 4 50 theme homocysteine 424:435 arg1 Hcy 443:445 free Hcy 438:445 free Hcy 438:445 In human plasma, there are several various forms of homocysteine: free Hcy, protein-bound Hcy (S-linked, and N-linked), and homocysteine thiolactone (HTL). 25701360 4 50 theme homocysteine 424:435 arg1 forms 415:419 several various forms 399:419 several various forms of homocysteine: free Hcy, protein-bound Hcy (S-linked, and N-linked), and homocysteine thiolactone (HTL) 399:525 In human plasma, there are several various forms of homocysteine: free Hcy, protein-bound Hcy (S-linked, and N-linked), and homocysteine thiolactone (HTL). 25701360 4 50 theme homocysteine 424:435 arg1 thiolactone 509:519 homocysteine thiolactone 496:519 homocysteine thiolactone (HTL) 496:525 In human plasma, there are several various forms of homocysteine: free Hcy, protein-bound Hcy (S-linked, and N-linked), and homocysteine thiolactone (HTL). 25701360 4 50 theme homocysteine 424:435 arg1 Hcy 462:464 protein-bound Hcy 448:464 protein-bound Hcy (S-linked, and N-linked) 448:489 In human plasma, there are several various forms of homocysteine: free Hcy, protein-bound Hcy (S-linked, and N-linked), and homocysteine thiolactone (HTL). 25701360 2 51 theme different 203:211 arg1 system 258:263 cardiovascular system 243:263 cardiovascular system 243:263 H2S plays a variety of roles in different biological systems, including cardiovascular system. 25701360 2 51 theme different 203:211 arg1 systems 224:230 different biological systems 203:230 different biological systems 203:230 H2S plays a variety of roles in different biological systems, including cardiovascular system. 25701360 3 52 contain contains 323:330 arg1 It 266:267 It 266:267 It 266:267 It is the final product of amino acids metabolism, which contains sulfur-cysteine and homocysteine (Hcy). 25701360 3 52 contain contains 323:330 arg2 homocysteine 352:363 homocysteine 352:363 homocysteine (Hcy) 352:369 It is the final product of amino acids metabolism, which contains sulfur-cysteine and homocysteine (Hcy). 25701360 3 52 contain contains 323:330 arg2 sulfur-cysteine 332:346 sulfur-cysteine 332:346 sulfur-cysteine 332:346 It is the final product of amino acids metabolism, which contains sulfur-cysteine and homocysteine (Hcy). 25701360 3 52 contain contains 323:330 arg1 product 282:288 the final product 272:288 the final product 272:288 It is the final product of amino acids metabolism, which contains sulfur-cysteine and homocysteine (Hcy). 25701360 3 52 contain contains 323:330 arg2 Hcy 366:368 Hcy 366:368 Hcy 366:368 It is the final product of amino acids metabolism, which contains sulfur-cysteine and homocysteine (Hcy). 25701360 9 53 from peroxidation 1394:1405 arg1 plasma 1410:1415 plasma 1410:1415 plasma preincubated with 1 mM Hcy or 1 µM HTL 1410:1454 The protective effect of 10 and 100 µM NaHS against the lipid peroxidation in plasma preincubated with 1 mM Hcy or 1 µM HTL was also observed. 25701360 9 54 theme µM 1449:1450 arg1 HTL 1452:1454 1 mM Hcy or 1 µM HTL 1435:1454 HTL 1452:1454 The protective effect of 10 and 100 µM NaHS against the lipid peroxidation in plasma preincubated with 1 mM Hcy or 1 µM HTL was also observed. 25701360 8 55 theme µM 1270:1271 arg1 HTL 1273:1275 1 µM HTL 1268:1275 1 µM HTL (when NaHS and Hcy/HTL were added to plasma together) 1268:1329 Our results indicate that 10 and 100 µM NaHS decreased the lipid peroxidation in plasma treated with 1 mM Hcy or 1 µM HTL (when NaHS and Hcy/HTL were added to plasma together). 25701360 4 56 dep Hcy 462:464 arg1 N-linked 481:488 N-linked 481:488 N-linked 481:488 In human plasma, there are several various forms of homocysteine: free Hcy, protein-bound Hcy (S-linked, and N-linked), and homocysteine thiolactone (HTL). 25701360 4 56 dep Hcy 462:464 arg1 S-linked 467:474 S-linked 467:474 S-linked 467:474 In human plasma, there are several various forms of homocysteine: free Hcy, protein-bound Hcy (S-linked, and N-linked), and homocysteine thiolactone (HTL). 25701360 7 57 theme sodium 913:918 arg1 NaHS 934:937 NaHS 934:937 NaHS 934:937 The aim of our study in vitro was to establish the influence of sodium hydrosulfide (NaHS, as a fast-releasing H2S donor; at tested concentrations: 10-1000 µM) on the plasma lipid peroxidation induced by the reduced Hcy (at final concentrations of 0.01-1 mM) and HTL (at final concentrations of 0.1-1 µM). 25701360 7 57 theme sodium 913:918 arg1 hydrosulfide 920:931 sodium hydrosulfide 913:931 sodium hydrosulfide (NaHS, as a fast-releasing H2S donor; at tested concentrations: 10-1000 µM) 913:1007 The aim of our study in vitro was to establish the influence of sodium hydrosulfide (NaHS, as a fast-releasing H2S donor; at tested concentrations: 10-1000 µM) on the plasma lipid peroxidation induced by the reduced Hcy (at final concentrations of 0.01-1 mM) and HTL (at final concentrations of 0.1-1 µM). 25701360 2 58 theme roles 194:198 arg1 roles 194:198 roles 194:198 roles 194:198 H2S plays a variety of roles in different biological systems, including cardiovascular system. 25701360 2 58 theme roles 194:198 arg1 variety 183:189 a variety 181:189 a variety of roles 181:198 H2S plays a variety of roles in different biological systems, including cardiovascular system. 25701360 8 59 theme 1 1256:1256 arg1 mM 1258:1259 mM 1258:1259 mM 1258:1259 Our results indicate that 10 and 100 µM NaHS decreased the lipid peroxidation in plasma treated with 1 mM Hcy or 1 µM HTL (when NaHS and Hcy/HTL were added to plasma together). 25701360 10 60 theme lipid 1541:1545 arg1 peroxidation 1547:1558 the lipid peroxidation 1537:1558 the lipid peroxidation (induced by different forms of homocysteine) 1537:1603 Considering the data presented in this study, we suggest that the lipid peroxidation (induced by different forms of homocysteine) may be reduced by hydrogen sulfide. 25701360 8 61 theme lipid 1214:1218 arg1 peroxidation 1220:1231 the lipid peroxidation 1210:1231 the lipid peroxidation in plasma treated with 1 mM Hcy or 1 µM HTL (when NaHS and Hcy/HTL were added to plasma together) 1210:1329 Our results indicate that 10 and 100 µM NaHS decreased the lipid peroxidation in plasma treated with 1 mM Hcy or 1 µM HTL (when NaHS and Hcy/HTL were added to plasma together). 25701360 2 62 theme cardiovascular 243:256 arg1 system 258:263 cardiovascular system 243:263 cardiovascular system 243:263 H2S plays a variety of roles in different biological systems, including cardiovascular system. 25701360 7 63 theme 0.01-1 1097:1102 arg1 mM 1104:1105 0.01-1 mM 1097:1105 0.01-1 mM 1097:1105 The aim of our study in vitro was to establish the influence of sodium hydrosulfide (NaHS, as a fast-releasing H2S donor; at tested concentrations: 10-1000 µM) on the plasma lipid peroxidation induced by the reduced Hcy (at final concentrations of 0.01-1 mM) and HTL (at final concentrations of 0.1-1 µM). 25701360 5 64 from thiolactone 600:610 arg1 form 587:590 the reduced form 575:590 the reduced form 575:590 Our previous works have shown that both Hcy in the reduced form and its thiolactone may modify fibrinolysis, coagulation process, and biological activity of blood platelets. 25701360 3 65 theme final 276:280 arg1 It 266:267 It 266:267 It 266:267 It is the final product of amino acids metabolism, which contains sulfur-cysteine and homocysteine (Hcy). 25701360 3 65 theme final 276:280 arg1 product 282:288 the final product 272:288 the final product 272:288 It is the final product of amino acids metabolism, which contains sulfur-cysteine and homocysteine (Hcy). 25701360 4 66 theme several 399:405 arg1 Hcy 443:445 free Hcy 438:445 free Hcy 438:445 In human plasma, there are several various forms of homocysteine: free Hcy, protein-bound Hcy (S-linked, and N-linked), and homocysteine thiolactone (HTL). 25701360 4 66 theme several 399:405 arg1 forms 415:419 several various forms 399:419 several various forms of homocysteine: free Hcy, protein-bound Hcy (S-linked, and N-linked), and homocysteine thiolactone (HTL) 399:525 In human plasma, there are several various forms of homocysteine: free Hcy, protein-bound Hcy (S-linked, and N-linked), and homocysteine thiolactone (HTL). 25701360 4 66 theme several 399:405 arg1 thiolactone 509:519 homocysteine thiolactone 496:519 homocysteine thiolactone (HTL) 496:525 In human plasma, there are several various forms of homocysteine: free Hcy, protein-bound Hcy (S-linked, and N-linked), and homocysteine thiolactone (HTL). 25701360 4 66 theme several 399:405 arg1 Hcy 462:464 protein-bound Hcy 448:464 protein-bound Hcy (S-linked, and N-linked) 448:489 In human plasma, there are several various forms of homocysteine: free Hcy, protein-bound Hcy (S-linked, and N-linked), and homocysteine thiolactone (HTL). 25701360 9 67 theme µM 1368:1369 arg1 NaHS 1371:1374 10 and 100 µM NaHS 1357:1374 10 and 100 µM NaHS 1357:1374 The protective effect of 10 and 100 µM NaHS against the lipid peroxidation in plasma preincubated with 1 mM Hcy or 1 µM HTL was also observed. 25701360 7 68 theme study 864:868 arg1 aim 853:855 The aim 849:855 The aim of our study in vitro 849:877 The aim of our study in vitro was to establish the influence of sodium hydrosulfide (NaHS, as a fast-releasing H2S donor; at tested concentrations: 10-1000 µM) on the plasma lipid peroxidation induced by the reduced Hcy (at final concentrations of 0.01-1 mM) and HTL (at final concentrations of 0.1-1 µM). 25701360 7 69 theme mM 1104:1105 arg1 concentrations 1079:1092 final concentrations 1073:1092 final concentrations of 0.01-1 mM 1073:1105 The aim of our study in vitro was to establish the influence of sodium hydrosulfide (NaHS, as a fast-releasing H2S donor; at tested concentrations: 10-1000 µM) on the plasma lipid peroxidation induced by the reduced Hcy (at final concentrations of 0.01-1 mM) and HTL (at final concentrations of 0.1-1 µM). 25701360 7 70 from influence 900:908 arg1 peroxidation 1029:1040 the plasma lipid peroxidation 1012:1040 the plasma lipid peroxidation induced by the reduced Hcy (at final concentrations of 0.01-1 mM) and HTL (at final concentrations of 0.1-1 µM) 1012:1152 The aim of our study in vitro was to establish the influence of sodium hydrosulfide (NaHS, as a fast-releasing H2S donor; at tested concentrations: 10-1000 µM) on the plasma lipid peroxidation induced by the reduced Hcy (at final concentrations of 0.01-1 mM) and HTL (at final concentrations of 0.1-1 µM). 25701360 9 71 theme NaHS 1371:1374 arg1 effect 1347:1352 The protective effect 1332:1352 The protective effect of 10 and 100 µM NaHS against the lipid peroxidation in plasma preincubated with 1 mM Hcy or 1 µM HTL 1332:1454 The protective effect of 10 and 100 µM NaHS against the lipid peroxidation in plasma preincubated with 1 mM Hcy or 1 µM HTL was also observed. 25701360 10 72 theme hydrogen 1623:1630 arg1 sulfide 1632:1638 hydrogen sulfide 1623:1638 hydrogen sulfide 1623:1638 Considering the data presented in this study, we suggest that the lipid peroxidation (induced by different forms of homocysteine) may be reduced by hydrogen sulfide. 25701360 8 73 dep HTL 1273:1275 arg1 added 1305:1309 added 1305:1309 were added to plasma together 1300:1328 Our results indicate that 10 and 100 µM NaHS decreased the lipid peroxidation in plasma treated with 1 mM Hcy or 1 µM HTL (when NaHS and Hcy/HTL were added to plasma together). 25701360 7 74 from concentrations 981:994 arg1 donor 964:968 a fast-releasing H2S donor; 943:969 a fast-releasing H2S donor; at tested concentrations 943:994 The aim of our study in vitro was to establish the influence of sodium hydrosulfide (NaHS, as a fast-releasing H2S donor; at tested concentrations: 10-1000 µM) on the plasma lipid peroxidation induced by the reduced Hcy (at final concentrations of 0.01-1 mM) and HTL (at final concentrations of 0.1-1 µM). 25701360 6 75 dep radicals 808:815 arg1 O 818:818 O 2 818:820 O 2 (-•) 818:825 Moreover, we have observed that HTL, like its precursor-Hcy stimulated the generation of superoxide anion radicals (O 2 (-•) ) in blood platelets. 25701360 6 75 dep radicals 808:815 arg1 -• 823:824 -• 823:824 -• 823:824 Moreover, we have observed that HTL, like its precursor-Hcy stimulated the generation of superoxide anion radicals (O 2 (-•) ) in blood platelets. 28632942 0 0 from mechanism 20:28 arg1 interactions 37:48 the interactions 33:48 the interactions of gp120 with CD4 and antibody 33:79 The glycan-mediated mechanism on the interactions of gp120 with CD4 and antibody: Insights from molecular dynamics simulation. 28632942 1 1 from antibodies 304:313 arg1 glycans 170:176 234 and 276 gp120 glycans 152:176 glycans 170:176 N-linked glycans such as 234 and 276 gp120 glycans are vital components of HIV evasion from humoral immunity and important for HIV-1 neutralization of many broadly neutralizing antibodies (bNAbs). 28632942 1 1 from antibodies 304:313 arg1 components 188:197 vital components 182:197 vital components of HIV evasion from humoral immunity and important for HIV-1 neutralization of many broadly neutralizing antibodies (bNAbs) 182:321 N-linked glycans such as 234 and 276 gp120 glycans are vital components of HIV evasion from humoral immunity and important for HIV-1 neutralization of many broadly neutralizing antibodies (bNAbs). 28632942 1 1 from antibodies 304:313 arg1 evasion 206:212 HIV evasion 202:212 HIV evasion from humoral immunity and important for HIV-1 neutralization of many broadly neutralizing antibodies (bNAbs) 202:321 N-linked glycans such as 234 and 276 gp120 glycans are vital components of HIV evasion from humoral immunity and important for HIV-1 neutralization of many broadly neutralizing antibodies (bNAbs). 28632942 1 1 from antibodies 304:313 arg1 glycans 136:142 N-linked glycans 127:142 N-linked glycans such as 234 and 276 gp120 glycans 127:176 N-linked glycans such as 234 and 276 gp120 glycans are vital components of HIV evasion from humoral immunity and important for HIV-1 neutralization of many broadly neutralizing antibodies (bNAbs). 28632942 6 2 with interactions 1297:1308 arg1 antibody 1332:1339 antibody 1332:1339 antibody 1332:1339 Through the structural analysis, it can be seen that 234 gp120 glycan leads to moving upward of two glycans and the variable region of heavy chain, which is favorable for the interactions of gp120 with CD4 and antibody. 28632942 6 2 with interactions 1297:1308 arg1 CD4 1324:1326 CD4 1324:1326 CD4 1324:1326 Through the structural analysis, it can be seen that 234 gp120 glycan leads to moving upward of two glycans and the variable region of heavy chain, which is favorable for the interactions of gp120 with CD4 and antibody. 28632942 4 3 theme gp120 849:853 arg1 interface 836:844 the binding interface 824:844 the binding interface of gp120, CD4 and antibody stable 824:878 Our results reveal that 276 gp120 glycan can enhance gp120-CD4 and gp120-antibody interactions through the formation of hydrogen bonds of the glycan with CD4 and antibody and make the binding interface of gp120, CD4 and antibody stable; 234 gp120 glycan primarily reinforces gp120-antibody interactions and weakly affects gp120-CD4 interactions as it mainly lies between gp120 and antibody. 28632942 6 4 theme variable 1238:1245 arg1 region 1247:1252 the variable region 1234:1252 the variable region of heavy chain, which is favorable for the interactions of gp120 with CD4 and antibody 1234:1339 Through the structural analysis, it can be seen that 234 gp120 glycan leads to moving upward of two glycans and the variable region of heavy chain, which is favorable for the interactions of gp120 with CD4 and antibody. 28632942 7 5 theme design 1410:1415 arg1 vaccines 1417:1424 design vaccines 1410:1424 design vaccines 1410:1424 The information obtained in this study can provide the guidance for design vaccines and small molecule inhibitors. 28632942 1 6 theme 234 152:154 arg1 glycans 170:176 234 and 276 gp120 glycans 152:176 glycans 170:176 N-linked glycans such as 234 and 276 gp120 glycans are vital components of HIV evasion from humoral immunity and important for HIV-1 neutralization of many broadly neutralizing antibodies (bNAbs). 28632942 4 7 with glycan 786:791 arg1 antibody 806:813 antibody 806:813 antibody 806:813 Our results reveal that 276 gp120 glycan can enhance gp120-CD4 and gp120-antibody interactions through the formation of hydrogen bonds of the glycan with CD4 and antibody and make the binding interface of gp120, CD4 and antibody stable; 234 gp120 glycan primarily reinforces gp120-antibody interactions and weakly affects gp120-CD4 interactions as it mainly lies between gp120 and antibody. 28632942 4 7 with glycan 786:791 arg1 CD4 798:800 CD4 798:800 CD4 798:800 Our results reveal that 276 gp120 glycan can enhance gp120-CD4 and gp120-antibody interactions through the formation of hydrogen bonds of the glycan with CD4 and antibody and make the binding interface of gp120, CD4 and antibody stable; 234 gp120 glycan primarily reinforces gp120-antibody interactions and weakly affects gp120-CD4 interactions as it mainly lies between gp120 and antibody. 28632942 6 8 theme glycans 1222:1228 arg1 region 1247:1252 the variable region 1234:1252 the variable region of heavy chain, which is favorable for the interactions of gp120 with CD4 and antibody 1234:1339 Through the structural analysis, it can be seen that 234 gp120 glycan leads to moving upward of two glycans and the variable region of heavy chain, which is favorable for the interactions of gp120 with CD4 and antibody. 28632942 6 8 theme glycans 1222:1228 arg1 upward 1208:1213 moving upward 1201:1213 moving upward of two glycans 1201:1228 Through the structural analysis, it can be seen that 234 gp120 glycan leads to moving upward of two glycans and the variable region of heavy chain, which is favorable for the interactions of gp120 with CD4 and antibody. 28632942 4 9 theme stable 873:878 arg1 antibody 864:871 antibody stable 864:878 antibody stable 864:878 Our results reveal that 276 gp120 glycan can enhance gp120-CD4 and gp120-antibody interactions through the formation of hydrogen bonds of the glycan with CD4 and antibody and make the binding interface of gp120, CD4 and antibody stable; 234 gp120 glycan primarily reinforces gp120-antibody interactions and weakly affects gp120-CD4 interactions as it mainly lies between gp120 and antibody. 28632942 5 10 theme gp120-CD4 1079:1087 arg1 associations 1108:1119 gp120-CD4 and gp120-antibody associations 1079:1119 gp120-CD4 and gp120-antibody associations 1079:1119 The co-operating of two glycans can enhance gp120-CD4 and gp120-antibody associations. 28632942 4 11 theme gp120-CD4 697:705 arg1 interactions 726:737 gp120-CD4 and gp120-antibody interactions 697:737 gp120-CD4 and gp120-antibody interactions 697:737 Our results reveal that 276 gp120 glycan can enhance gp120-CD4 and gp120-antibody interactions through the formation of hydrogen bonds of the glycan with CD4 and antibody and make the binding interface of gp120, CD4 and antibody stable; 234 gp120 glycan primarily reinforces gp120-antibody interactions and weakly affects gp120-CD4 interactions as it mainly lies between gp120 and antibody. 28632942 1 12 theme important 240:248 arg1 bNAbs 316:320 bNAbs 316:320 bNAbs 316:320 N-linked glycans such as 234 and 276 gp120 glycans are vital components of HIV evasion from humoral immunity and important for HIV-1 neutralization of many broadly neutralizing antibodies (bNAbs). 28632942 1 12 theme important 240:248 arg1 antibodies 304:313 broadly neutralizing antibodies 283:313 important for HIV-1 neutralization of many broadly neutralizing antibodies (bNAbs) 240:321 N-linked glycans such as 234 and 276 gp120 glycans are vital components of HIV evasion from humoral immunity and important for HIV-1 neutralization of many broadly neutralizing antibodies (bNAbs). 28632942 4 13 theme antibody 864:871 arg1 interface 836:844 the binding interface 824:844 the binding interface of gp120, CD4 and antibody stable 824:878 Our results reveal that 276 gp120 glycan can enhance gp120-CD4 and gp120-antibody interactions through the formation of hydrogen bonds of the glycan with CD4 and antibody and make the binding interface of gp120, CD4 and antibody stable; 234 gp120 glycan primarily reinforces gp120-antibody interactions and weakly affects gp120-CD4 interactions as it mainly lies between gp120 and antibody. 28632942 6 14 theme structural 1134:1143 arg1 analysis 1145:1152 the structural analysis 1130:1152 the structural analysis 1130:1152 Through the structural analysis, it can be seen that 234 gp120 glycan leads to moving upward of two glycans and the variable region of heavy chain, which is favorable for the interactions of gp120 with CD4 and antibody. 28632942 0 15 theme molecular 96:104 arg1 simulation 115:124 molecular dynamics simulation 96:124 molecular dynamics simulation 96:124 The glycan-mediated mechanism on the interactions of gp120 with CD4 and antibody: Insights from molecular dynamics simulation. 28632942 3 16 with interactions 431:442 arg1 antibody 466:473 antibody 466:473 antibody 466:473 To investigate the roles of the glycans on the interactions of gp120 with CD4 and antibody, molecular dynamic simulations based on gp120-CD4-8ANC195 complex with 234 and 276 gp120 glycans, 234 gp120 glycan, 276 gp120 glycan, and without glycan were performed. 28632942 3 16 with interactions 431:442 arg1 CD4 458:460 CD4 458:460 CD4 458:460 To investigate the roles of the glycans on the interactions of gp120 with CD4 and antibody, molecular dynamic simulations based on gp120-CD4-8ANC195 complex with 234 and 276 gp120 glycans, 234 gp120 glycan, 276 gp120 glycan, and without glycan were performed. 28632942 0 17 dep Insights 82:89 arg1 mechanism 20:28 The glycan-mediated mechanism 0:28 The glycan-mediated mechanism on the interactions of gp120 with CD4 and antibody 0:79 The glycan-mediated mechanism on the interactions of gp120 with CD4 and antibody: Insights from molecular dynamics simulation. 28632942 2 18 theme action 351:356 arg1 mechanism 358:366 the action mechanism 347:366 the action mechanism of two glycans 347:381 However, it is unknown the action mechanism of two glycans. 28632942 5 19 theme glycans 1059:1065 arg1 co-operating 1039:1050 co-operating 1039:1050 co-operating 1039:1050 The co-operating of two glycans can enhance gp120-CD4 and gp120-antibody associations. 28632942 3 20 theme dynamic 486:492 arg1 simulations 494:504 molecular dynamic simulations 476:504 molecular dynamic simulations based on gp120-CD4-8ANC195 complex with 234 and 276 gp120 glycans, 234 gp120 glycan, 276 gp120 glycan, and without glycan 476:626 To investigate the roles of the glycans on the interactions of gp120 with CD4 and antibody, molecular dynamic simulations based on gp120-CD4-8ANC195 complex with 234 and 276 gp120 glycans, 234 gp120 glycan, 276 gp120 glycan, and without glycan were performed. 28632942 1 21 theme 276 160:162 arg1 glycans 170:176 234 and 276 gp120 glycans 152:176 glycans 170:176 N-linked glycans such as 234 and 276 gp120 glycans are vital components of HIV evasion from humoral immunity and important for HIV-1 neutralization of many broadly neutralizing antibodies (bNAbs). 28632942 0 22 theme glycan-mediated 4:18 arg1 mechanism 20:28 The glycan-mediated mechanism 0:28 The glycan-mediated mechanism on the interactions of gp120 with CD4 and antibody 0:79 The glycan-mediated mechanism on the interactions of gp120 with CD4 and antibody: Insights from molecular dynamics simulation. 28632942 6 23 theme gp120 1179:1183 arg1 glycan 1185:1190 234 gp120 glycan 1175:1190 234 gp120 glycan 1175:1190 Through the structural analysis, it can be seen that 234 gp120 glycan leads to moving upward of two glycans and the variable region of heavy chain, which is favorable for the interactions of gp120 with CD4 and antibody. 28632942 4 24 theme gp120 672:676 arg1 glycan 678:683 276 gp120 glycan 668:683 276 gp120 glycan 668:683 Our results reveal that 276 gp120 glycan can enhance gp120-CD4 and gp120-antibody interactions through the formation of hydrogen bonds of the glycan with CD4 and antibody and make the binding interface of gp120, CD4 and antibody stable; 234 gp120 glycan primarily reinforces gp120-antibody interactions and weakly affects gp120-CD4 interactions as it mainly lies between gp120 and antibody. 28632942 3 25 theme molecular 476:484 arg1 simulations 494:504 molecular dynamic simulations 476:504 molecular dynamic simulations based on gp120-CD4-8ANC195 complex with 234 and 276 gp120 glycans, 234 gp120 glycan, 276 gp120 glycan, and without glycan 476:626 To investigate the roles of the glycans on the interactions of gp120 with CD4 and antibody, molecular dynamic simulations based on gp120-CD4-8ANC195 complex with 234 and 276 gp120 glycans, 234 gp120 glycan, 276 gp120 glycan, and without glycan were performed. 28632942 1 26 theme gp120 164:168 arg1 glycans 170:176 234 and 276 gp120 glycans 152:176 glycans 170:176 N-linked glycans such as 234 and 276 gp120 glycans are vital components of HIV evasion from humoral immunity and important for HIV-1 neutralization of many broadly neutralizing antibodies (bNAbs). 28632942 6 27 theme heavy 1257:1261 arg1 chain 1263:1267 heavy chain 1257:1267 heavy chain 1257:1267 Through the structural analysis, it can be seen that 234 gp120 glycan leads to moving upward of two glycans and the variable region of heavy chain, which is favorable for the interactions of gp120 with CD4 and antibody. 28632942 1 28 theme HIV-1 254:258 arg1 neutralization 260:273 HIV-1 neutralization 254:273 HIV-1 neutralization of many 254:281 N-linked glycans such as 234 and 276 gp120 glycans are vital components of HIV evasion from humoral immunity and important for HIV-1 neutralization of many broadly neutralizing antibodies (bNAbs). 28632942 4 29 theme glycan 786:791 arg1 formation 751:759 the formation 747:759 the formation of hydrogen bonds of the glycan with CD4 and antibody 747:813 Our results reveal that 276 gp120 glycan can enhance gp120-CD4 and gp120-antibody interactions through the formation of hydrogen bonds of the glycan with CD4 and antibody and make the binding interface of gp120, CD4 and antibody stable; 234 gp120 glycan primarily reinforces gp120-antibody interactions and weakly affects gp120-CD4 interactions as it mainly lies between gp120 and antibody. 28632942 6 30 theme chain 1263:1267 arg1 region 1247:1252 the variable region 1234:1252 the variable region of heavy chain, which is favorable for the interactions of gp120 with CD4 and antibody 1234:1339 Through the structural analysis, it can be seen that 234 gp120 glycan leads to moving upward of two glycans and the variable region of heavy chain, which is favorable for the interactions of gp120 with CD4 and antibody. 28632942 6 30 theme chain 1263:1267 arg1 upward 1208:1213 moving upward 1201:1213 moving upward of two glycans 1201:1228 Through the structural analysis, it can be seen that 234 gp120 glycan leads to moving upward of two glycans and the variable region of heavy chain, which is favorable for the interactions of gp120 with CD4 and antibody. 28632942 3 31 with complex 533:539 arg1 glycan 583:588 234 gp120 glycan 573:588 234 gp120 glycan 573:588 To investigate the roles of the glycans on the interactions of gp120 with CD4 and antibody, molecular dynamic simulations based on gp120-CD4-8ANC195 complex with 234 and 276 gp120 glycans, 234 gp120 glycan, 276 gp120 glycan, and without glycan were performed. 28632942 3 31 with complex 533:539 arg1 glycan 601:606 276 gp120 glycan 591:606 276 gp120 glycan 591:606 To investigate the roles of the glycans on the interactions of gp120 with CD4 and antibody, molecular dynamic simulations based on gp120-CD4-8ANC195 complex with 234 and 276 gp120 glycans, 234 gp120 glycan, 276 gp120 glycan, and without glycan were performed. 28632942 3 31 with complex 533:539 arg1 glycans 564:570 234 and 276 gp120 glycans 546:570 glycans 564:570 To investigate the roles of the glycans on the interactions of gp120 with CD4 and antibody, molecular dynamic simulations based on gp120-CD4-8ANC195 complex with 234 and 276 gp120 glycans, 234 gp120 glycan, 276 gp120 glycan, and without glycan were performed. 28632942 4 32 theme hydrogen 764:771 arg1 bonds 773:777 hydrogen bonds 764:777 hydrogen bonds 764:777 Our results reveal that 276 gp120 glycan can enhance gp120-CD4 and gp120-antibody interactions through the formation of hydrogen bonds of the glycan with CD4 and antibody and make the binding interface of gp120, CD4 and antibody stable; 234 gp120 glycan primarily reinforces gp120-antibody interactions and weakly affects gp120-CD4 interactions as it mainly lies between gp120 and antibody. 28632942 0 33 theme dynamics 106:113 arg1 simulation 115:124 molecular dynamics simulation 96:124 molecular dynamics simulation 96:124 The glycan-mediated mechanism on the interactions of gp120 with CD4 and antibody: Insights from molecular dynamics simulation. 28632942 3 34 theme 276 591:593 arg1 gp120 595:599 gp120 595:599 gp120 595:599 To investigate the roles of the glycans on the interactions of gp120 with CD4 and antibody, molecular dynamic simulations based on gp120-CD4-8ANC195 complex with 234 and 276 gp120 glycans, 234 gp120 glycan, 276 gp120 glycan, and without glycan were performed. 28632942 3 35 theme gp120-CD4-8ANC195 515:531 arg1 complex 533:539 gp120-CD4-8ANC195 complex 515:539 gp120-CD4-8ANC195 complex with 234 and 276 gp120 glycans, 234 gp120 glycan, 276 gp120 glycan, and without glycan 515:626 To investigate the roles of the glycans on the interactions of gp120 with CD4 and antibody, molecular dynamic simulations based on gp120-CD4-8ANC195 complex with 234 and 276 gp120 glycans, 234 gp120 glycan, 276 gp120 glycan, and without glycan were performed. 28632942 1 36 theme vital 182:186 arg1 glycans 170:176 234 and 276 gp120 glycans 152:176 glycans 170:176 N-linked glycans such as 234 and 276 gp120 glycans are vital components of HIV evasion from humoral immunity and important for HIV-1 neutralization of many broadly neutralizing antibodies (bNAbs). 28632942 1 36 theme vital 182:186 arg1 components 188:197 vital components 182:197 vital components of HIV evasion from humoral immunity and important for HIV-1 neutralization of many broadly neutralizing antibodies (bNAbs) 182:321 N-linked glycans such as 234 and 276 gp120 glycans are vital components of HIV evasion from humoral immunity and important for HIV-1 neutralization of many broadly neutralizing antibodies (bNAbs). 28632942 1 36 theme vital 182:186 arg1 glycans 136:142 N-linked glycans 127:142 N-linked glycans such as 234 and 276 gp120 glycans 127:176 N-linked glycans such as 234 and 276 gp120 glycans are vital components of HIV evasion from humoral immunity and important for HIV-1 neutralization of many broadly neutralizing antibodies (bNAbs). 28632942 1 37 theme many 278:281 arg1 neutralization 260:273 HIV-1 neutralization 254:273 HIV-1 neutralization of many 254:281 N-linked glycans such as 234 and 276 gp120 glycans are vital components of HIV evasion from humoral immunity and important for HIV-1 neutralization of many broadly neutralizing antibodies (bNAbs). 28632942 1 38 from immunity 227:234 arg1 glycans 170:176 234 and 276 gp120 glycans 152:176 glycans 170:176 N-linked glycans such as 234 and 276 gp120 glycans are vital components of HIV evasion from humoral immunity and important for HIV-1 neutralization of many broadly neutralizing antibodies (bNAbs). 28632942 1 38 from immunity 227:234 arg1 components 188:197 vital components 182:197 vital components of HIV evasion from humoral immunity and important for HIV-1 neutralization of many broadly neutralizing antibodies (bNAbs) 182:321 N-linked glycans such as 234 and 276 gp120 glycans are vital components of HIV evasion from humoral immunity and important for HIV-1 neutralization of many broadly neutralizing antibodies (bNAbs). 28632942 1 38 from immunity 227:234 arg1 evasion 206:212 HIV evasion 202:212 HIV evasion from humoral immunity and important for HIV-1 neutralization of many broadly neutralizing antibodies (bNAbs) 202:321 N-linked glycans such as 234 and 276 gp120 glycans are vital components of HIV evasion from humoral immunity and important for HIV-1 neutralization of many broadly neutralizing antibodies (bNAbs). 28632942 1 38 from immunity 227:234 arg1 glycans 136:142 N-linked glycans 127:142 N-linked glycans such as 234 and 276 gp120 glycans 127:176 N-linked glycans such as 234 and 276 gp120 glycans are vital components of HIV evasion from humoral immunity and important for HIV-1 neutralization of many broadly neutralizing antibodies (bNAbs). 28632942 3 39 theme gp120 595:599 arg1 glycans 564:570 234 and 276 gp120 glycans 546:570 glycans 564:570 To investigate the roles of the glycans on the interactions of gp120 with CD4 and antibody, molecular dynamic simulations based on gp120-CD4-8ANC195 complex with 234 and 276 gp120 glycans, 234 gp120 glycan, 276 gp120 glycan, and without glycan were performed. 28632942 3 39 theme gp120 595:599 arg1 glycan 601:606 276 gp120 glycan 591:606 276 gp120 glycan 591:606 To investigate the roles of the glycans on the interactions of gp120 with CD4 and antibody, molecular dynamic simulations based on gp120-CD4-8ANC195 complex with 234 and 276 gp120 glycans, 234 gp120 glycan, 276 gp120 glycan, and without glycan were performed. 28632942 3 40 theme 276 554:556 arg1 glycan 583:588 234 gp120 glycan 573:588 234 gp120 glycan 573:588 To investigate the roles of the glycans on the interactions of gp120 with CD4 and antibody, molecular dynamic simulations based on gp120-CD4-8ANC195 complex with 234 and 276 gp120 glycans, 234 gp120 glycan, 276 gp120 glycan, and without glycan were performed. 28632942 3 40 theme 276 554:556 arg1 glycan 601:606 276 gp120 glycan 591:606 276 gp120 glycan 591:606 To investigate the roles of the glycans on the interactions of gp120 with CD4 and antibody, molecular dynamic simulations based on gp120-CD4-8ANC195 complex with 234 and 276 gp120 glycans, 234 gp120 glycan, 276 gp120 glycan, and without glycan were performed. 28632942 3 40 theme 276 554:556 arg1 glycans 564:570 234 and 276 gp120 glycans 546:570 glycans 564:570 To investigate the roles of the glycans on the interactions of gp120 with CD4 and antibody, molecular dynamic simulations based on gp120-CD4-8ANC195 complex with 234 and 276 gp120 glycans, 234 gp120 glycan, 276 gp120 glycan, and without glycan were performed. 28632942 2 41 theme glycans 375:381 arg1 mechanism 358:366 the action mechanism 347:366 the action mechanism of two glycans 347:381 However, it is unknown the action mechanism of two glycans. 28632942 4 42 theme gp120-antibody 919:932 arg1 interactions 934:945 gp120-antibody interactions 919:945 gp120-antibody interactions 919:945 Our results reveal that 276 gp120 glycan can enhance gp120-CD4 and gp120-antibody interactions through the formation of hydrogen bonds of the glycan with CD4 and antibody and make the binding interface of gp120, CD4 and antibody stable; 234 gp120 glycan primarily reinforces gp120-antibody interactions and weakly affects gp120-CD4 interactions as it mainly lies between gp120 and antibody. 28632942 4 43 theme CD4 856:858 arg1 interface 836:844 the binding interface 824:844 the binding interface of gp120, CD4 and antibody stable 824:878 Our results reveal that 276 gp120 glycan can enhance gp120-CD4 and gp120-antibody interactions through the formation of hydrogen bonds of the glycan with CD4 and antibody and make the binding interface of gp120, CD4 and antibody stable; 234 gp120 glycan primarily reinforces gp120-antibody interactions and weakly affects gp120-CD4 interactions as it mainly lies between gp120 and antibody. 28632942 7 44 theme molecule 1436:1443 arg1 inhibitors 1445:1454 small molecule inhibitors 1430:1454 small molecule inhibitors 1430:1454 The information obtained in this study can provide the guidance for design vaccines and small molecule inhibitors. 28632942 3 45 theme gp120 558:562 arg1 glycan 583:588 234 gp120 glycan 573:588 234 gp120 glycan 573:588 To investigate the roles of the glycans on the interactions of gp120 with CD4 and antibody, molecular dynamic simulations based on gp120-CD4-8ANC195 complex with 234 and 276 gp120 glycans, 234 gp120 glycan, 276 gp120 glycan, and without glycan were performed. 28632942 3 45 theme gp120 558:562 arg1 glycan 601:606 276 gp120 glycan 591:606 276 gp120 glycan 591:606 To investigate the roles of the glycans on the interactions of gp120 with CD4 and antibody, molecular dynamic simulations based on gp120-CD4-8ANC195 complex with 234 and 276 gp120 glycans, 234 gp120 glycan, 276 gp120 glycan, and without glycan were performed. 28632942 3 45 theme gp120 558:562 arg1 glycans 564:570 234 and 276 gp120 glycans 546:570 glycans 564:570 To investigate the roles of the glycans on the interactions of gp120 with CD4 and antibody, molecular dynamic simulations based on gp120-CD4-8ANC195 complex with 234 and 276 gp120 glycans, 234 gp120 glycan, 276 gp120 glycan, and without glycan were performed. 28632942 1 46 from components 188:197 arg1 bNAbs 316:320 bNAbs 316:320 bNAbs 316:320 N-linked glycans such as 234 and 276 gp120 glycans are vital components of HIV evasion from humoral immunity and important for HIV-1 neutralization of many broadly neutralizing antibodies (bNAbs). 28632942 1 46 from components 188:197 arg1 antibodies 304:313 broadly neutralizing antibodies 283:313 important for HIV-1 neutralization of many broadly neutralizing antibodies (bNAbs) 240:321 N-linked glycans such as 234 and 276 gp120 glycans are vital components of HIV evasion from humoral immunity and important for HIV-1 neutralization of many broadly neutralizing antibodies (bNAbs). 28632942 1 46 from components 188:197 arg1 immunity 227:234 humoral immunity 219:234 humoral immunity 219:234 N-linked glycans such as 234 and 276 gp120 glycans are vital components of HIV evasion from humoral immunity and important for HIV-1 neutralization of many broadly neutralizing antibodies (bNAbs). 28632942 3 47 theme glycans 416:422 arg1 roles 403:407 the roles 399:407 the roles of the glycans on the interactions of gp120 with CD4 and antibody 399:473 To investigate the roles of the glycans on the interactions of gp120 with CD4 and antibody, molecular dynamic simulations based on gp120-CD4-8ANC195 complex with 234 and 276 gp120 glycans, 234 gp120 glycan, 276 gp120 glycan, and without glycan were performed. 28632942 0 48 theme gp120 53:57 arg1 interactions 37:48 the interactions 33:48 the interactions of gp120 with CD4 and antibody 33:79 The glycan-mediated mechanism on the interactions of gp120 with CD4 and antibody: Insights from molecular dynamics simulation. 28632942 1 49 theme neutralizing 291:302 arg1 bNAbs 316:320 bNAbs 316:320 bNAbs 316:320 N-linked glycans such as 234 and 276 gp120 glycans are vital components of HIV evasion from humoral immunity and important for HIV-1 neutralization of many broadly neutralizing antibodies (bNAbs). 28632942 1 49 theme neutralizing 291:302 arg1 antibodies 304:313 broadly neutralizing antibodies 283:313 important for HIV-1 neutralization of many broadly neutralizing antibodies (bNAbs) 240:321 N-linked glycans such as 234 and 276 gp120 glycans are vital components of HIV evasion from humoral immunity and important for HIV-1 neutralization of many broadly neutralizing antibodies (bNAbs). 28632942 4 50 theme binding 828:834 arg1 interface 836:844 the binding interface 824:844 the binding interface of gp120, CD4 and antibody stable 824:878 Our results reveal that 276 gp120 glycan can enhance gp120-CD4 and gp120-antibody interactions through the formation of hydrogen bonds of the glycan with CD4 and antibody and make the binding interface of gp120, CD4 and antibody stable; 234 gp120 glycan primarily reinforces gp120-antibody interactions and weakly affects gp120-CD4 interactions as it mainly lies between gp120 and antibody. 28632942 3 51 theme 234 546:548 arg1 glycan 583:588 234 gp120 glycan 573:588 234 gp120 glycan 573:588 To investigate the roles of the glycans on the interactions of gp120 with CD4 and antibody, molecular dynamic simulations based on gp120-CD4-8ANC195 complex with 234 and 276 gp120 glycans, 234 gp120 glycan, 276 gp120 glycan, and without glycan were performed. 28632942 3 51 theme 234 546:548 arg1 glycan 601:606 276 gp120 glycan 591:606 276 gp120 glycan 591:606 To investigate the roles of the glycans on the interactions of gp120 with CD4 and antibody, molecular dynamic simulations based on gp120-CD4-8ANC195 complex with 234 and 276 gp120 glycans, 234 gp120 glycan, 276 gp120 glycan, and without glycan were performed. 28632942 3 51 theme 234 546:548 arg1 glycans 564:570 234 and 276 gp120 glycans 546:570 glycans 564:570 To investigate the roles of the glycans on the interactions of gp120 with CD4 and antibody, molecular dynamic simulations based on gp120-CD4-8ANC195 complex with 234 and 276 gp120 glycans, 234 gp120 glycan, 276 gp120 glycan, and without glycan were performed. 28632942 3 52 theme gp120 447:451 arg1 interactions 431:442 the interactions 427:442 the interactions of gp120 with CD4 and antibody 427:473 To investigate the roles of the glycans on the interactions of gp120 with CD4 and antibody, molecular dynamic simulations based on gp120-CD4-8ANC195 complex with 234 and 276 gp120 glycans, 234 gp120 glycan, 276 gp120 glycan, and without glycan were performed. 28632942 1 53 link N-linked 127:134 arg1 glycans 170:176 234 and 276 gp120 glycans 152:176 glycans 170:176 N-linked glycans such as 234 and 276 gp120 glycans are vital components of HIV evasion from humoral immunity and important for HIV-1 neutralization of many broadly neutralizing antibodies (bNAbs). 28632942 1 53 link N-linked 127:134 arg1 components 188:197 vital components 182:197 vital components of HIV evasion from humoral immunity and important for HIV-1 neutralization of many broadly neutralizing antibodies (bNAbs) 182:321 N-linked glycans such as 234 and 276 gp120 glycans are vital components of HIV evasion from humoral immunity and important for HIV-1 neutralization of many broadly neutralizing antibodies (bNAbs). 28632942 1 53 link N-linked 127:134 arg1 glycans 136:142 N-linked glycans 127:142 N-linked glycans such as 234 and 276 gp120 glycans 127:176 N-linked glycans such as 234 and 276 gp120 glycans are vital components of HIV evasion from humoral immunity and important for HIV-1 neutralization of many broadly neutralizing antibodies (bNAbs). 28632942 4 54 theme bonds 773:777 arg1 formation 751:759 the formation 747:759 the formation of hydrogen bonds of the glycan with CD4 and antibody 747:813 Our results reveal that 276 gp120 glycan can enhance gp120-CD4 and gp120-antibody interactions through the formation of hydrogen bonds of the glycan with CD4 and antibody and make the binding interface of gp120, CD4 and antibody stable; 234 gp120 glycan primarily reinforces gp120-antibody interactions and weakly affects gp120-CD4 interactions as it mainly lies between gp120 and antibody. 28632942 7 55 theme small 1430:1434 arg1 inhibitors 1445:1454 small molecule inhibitors 1430:1454 small molecule inhibitors 1430:1454 The information obtained in this study can provide the guidance for design vaccines and small molecule inhibitors. 28632942 3 56 from roles 403:407 arg1 interactions 431:442 the interactions 427:442 the interactions of gp120 with CD4 and antibody 427:473 To investigate the roles of the glycans on the interactions of gp120 with CD4 and antibody, molecular dynamic simulations based on gp120-CD4-8ANC195 complex with 234 and 276 gp120 glycans, 234 gp120 glycan, 276 gp120 glycan, and without glycan were performed. 28632942 1 57 theme HIV 202:204 arg1 evasion 206:212 HIV evasion 202:212 HIV evasion from humoral immunity and important for HIV-1 neutralization of many broadly neutralizing antibodies (bNAbs) 202:321 N-linked glycans such as 234 and 276 gp120 glycans are vital components of HIV evasion from humoral immunity and important for HIV-1 neutralization of many broadly neutralizing antibodies (bNAbs). 28632942 4 58 theme gp120-antibody 711:724 arg1 interactions 726:737 gp120-CD4 and gp120-antibody interactions 697:737 gp120-CD4 and gp120-antibody interactions 697:737 Our results reveal that 276 gp120 glycan can enhance gp120-CD4 and gp120-antibody interactions through the formation of hydrogen bonds of the glycan with CD4 and antibody and make the binding interface of gp120, CD4 and antibody stable; 234 gp120 glycan primarily reinforces gp120-antibody interactions and weakly affects gp120-CD4 interactions as it mainly lies between gp120 and antibody. 28632942 6 59 theme moving 1201:1206 arg1 upward 1208:1213 moving upward 1201:1213 moving upward of two glycans 1201:1228 Through the structural analysis, it can be seen that 234 gp120 glycan leads to moving upward of two glycans and the variable region of heavy chain, which is favorable for the interactions of gp120 with CD4 and antibody. 28632942 3 60 theme gp120 577:581 arg1 glycan 583:588 234 gp120 glycan 573:588 234 gp120 glycan 573:588 To investigate the roles of the glycans on the interactions of gp120 with CD4 and antibody, molecular dynamic simulations based on gp120-CD4-8ANC195 complex with 234 and 276 gp120 glycans, 234 gp120 glycan, 276 gp120 glycan, and without glycan were performed. 28632942 3 60 theme gp120 577:581 arg1 glycans 564:570 234 and 276 gp120 glycans 546:570 glycans 564:570 To investigate the roles of the glycans on the interactions of gp120 with CD4 and antibody, molecular dynamic simulations based on gp120-CD4-8ANC195 complex with 234 and 276 gp120 glycans, 234 gp120 glycan, 276 gp120 glycan, and without glycan were performed. 28632942 1 61 theme N-linked 127:134 arg1 glycans 170:176 234 and 276 gp120 glycans 152:176 glycans 170:176 N-linked glycans such as 234 and 276 gp120 glycans are vital components of HIV evasion from humoral immunity and important for HIV-1 neutralization of many broadly neutralizing antibodies (bNAbs). 28632942 1 61 theme N-linked 127:134 arg1 components 188:197 vital components 182:197 vital components of HIV evasion from humoral immunity and important for HIV-1 neutralization of many broadly neutralizing antibodies (bNAbs) 182:321 N-linked glycans such as 234 and 276 gp120 glycans are vital components of HIV evasion from humoral immunity and important for HIV-1 neutralization of many broadly neutralizing antibodies (bNAbs). 28632942 1 61 theme N-linked 127:134 arg1 glycans 136:142 N-linked glycans 127:142 N-linked glycans such as 234 and 276 gp120 glycans 127:176 N-linked glycans such as 234 and 276 gp120 glycans are vital components of HIV evasion from humoral immunity and important for HIV-1 neutralization of many broadly neutralizing antibodies (bNAbs). 28632942 1 62 theme evasion 206:212 arg1 glycans 170:176 234 and 276 gp120 glycans 152:176 glycans 170:176 N-linked glycans such as 234 and 276 gp120 glycans are vital components of HIV evasion from humoral immunity and important for HIV-1 neutralization of many broadly neutralizing antibodies (bNAbs). 28632942 1 62 theme evasion 206:212 arg1 components 188:197 vital components 182:197 vital components of HIV evasion from humoral immunity and important for HIV-1 neutralization of many broadly neutralizing antibodies (bNAbs) 182:321 N-linked glycans such as 234 and 276 gp120 glycans are vital components of HIV evasion from humoral immunity and important for HIV-1 neutralization of many broadly neutralizing antibodies (bNAbs). 28632942 1 62 theme evasion 206:212 arg1 glycans 136:142 N-linked glycans 127:142 N-linked glycans such as 234 and 276 gp120 glycans 127:176 N-linked glycans such as 234 and 276 gp120 glycans are vital components of HIV evasion from humoral immunity and important for HIV-1 neutralization of many broadly neutralizing antibodies (bNAbs). 28632942 6 63 theme gp120 1313:1317 arg1 interactions 1297:1308 the interactions 1293:1308 the interactions of gp120 with CD4 and antibody 1293:1339 Through the structural analysis, it can be seen that 234 gp120 glycan leads to moving upward of two glycans and the variable region of heavy chain, which is favorable for the interactions of gp120 with CD4 and antibody. 28632942 0 64 from simulation 115:124 arg1 Insights 82:89 Insights 82:89 Insights from molecular dynamics simulation 82:124 The glycan-mediated mechanism on the interactions of gp120 with CD4 and antibody: Insights from molecular dynamics simulation. 28632942 4 65 theme gp120 885:889 arg1 glycan 891:896 234 gp120 glycan 881:896 234 gp120 glycan 881:896 Our results reveal that 276 gp120 glycan can enhance gp120-CD4 and gp120-antibody interactions through the formation of hydrogen bonds of the glycan with CD4 and antibody and make the binding interface of gp120, CD4 and antibody stable; 234 gp120 glycan primarily reinforces gp120-antibody interactions and weakly affects gp120-CD4 interactions as it mainly lies between gp120 and antibody. 28632942 5 66 theme gp120-antibody 1093:1106 arg1 associations 1108:1119 gp120-CD4 and gp120-antibody associations 1079:1119 gp120-CD4 and gp120-antibody associations 1079:1119 The co-operating of two glycans can enhance gp120-CD4 and gp120-antibody associations. 28632942 0 67 with interactions 37:48 arg1 antibody 72:79 antibody 72:79 antibody 72:79 The glycan-mediated mechanism on the interactions of gp120 with CD4 and antibody: Insights from molecular dynamics simulation. 28632942 0 67 with interactions 37:48 arg1 CD4 64:66 CD4 64:66 CD4 64:66 The glycan-mediated mechanism on the interactions of gp120 with CD4 and antibody: Insights from molecular dynamics simulation. 28632942 4 68 theme gp120-CD4 966:974 arg1 interactions 976:987 gp120-CD4 interactions 966:987 gp120-CD4 interactions 966:987 Our results reveal that 276 gp120 glycan can enhance gp120-CD4 and gp120-antibody interactions through the formation of hydrogen bonds of the glycan with CD4 and antibody and make the binding interface of gp120, CD4 and antibody stable; 234 gp120 glycan primarily reinforces gp120-antibody interactions and weakly affects gp120-CD4 interactions as it mainly lies between gp120 and antibody. 28632942 1 69 theme humoral 219:225 arg1 immunity 227:234 humoral immunity 219:234 humoral immunity 219:234 N-linked glycans such as 234 and 276 gp120 glycans are vital components of HIV evasion from humoral immunity and important for HIV-1 neutralization of many broadly neutralizing antibodies (bNAbs). 27891772 7 0 from injection 1529:1537 arg1 variation 1584:1592 technical variation 1574:1592 technical variation 1574:1592 The described twoplex 12 C6 /13 C6 aniline 2D LC-MS platform is ideally suited for differential glycomic analysis of structurally complex N-glycan pools due to combination and analysis of samples in a single LC-MS injection and the associated minimization in technical variation. 27891772 7 0 from injection 1529:1537 arg1 analysis 1491:1498 analysis 1491:1498 analysis 1491:1498 The described twoplex 12 C6 /13 C6 aniline 2D LC-MS platform is ideally suited for differential glycomic analysis of structurally complex N-glycan pools due to combination and analysis of samples in a single LC-MS injection and the associated minimization in technical variation. 27891772 7 0 from injection 1529:1537 arg1 combination 1475:1485 combination 1475:1485 combination 1475:1485 The described twoplex 12 C6 /13 C6 aniline 2D LC-MS platform is ideally suited for differential glycomic analysis of structurally complex N-glycan pools due to combination and analysis of samples in a single LC-MS injection and the associated minimization in technical variation. 27891772 7 1 theme twoplex 1329:1335 arg1 platform 1367:1374 The described twoplex 12 C6 /13 C6 aniline 2D LC-MS platform 1315:1374 The described twoplex 12 C6 /13 C6 aniline 2D LC-MS platform 1315:1374 The described twoplex 12 C6 /13 C6 aniline 2D LC-MS platform is ideally suited for differential glycomic analysis of structurally complex N-glycan pools due to combination and analysis of samples in a single LC-MS injection and the associated minimization in technical variation. 27891772 2 2 theme complex 420:426 arg1 samples 435:441 complex glycan samples 420:441 complex glycan samples 420:441 Commonly used analytical platforms for comparative relative quantitation of complex glycan samples include MALDI-TOF-MS or chromatographic glycan profiling with subsequent data alignment and statistical evaluation. 27891772 2 3 with profiling 490:498 arg1 alignment 521:529 subsequent data alignment 505:529 subsequent data alignment 505:529 Commonly used analytical platforms for comparative relative quantitation of complex glycan samples include MALDI-TOF-MS or chromatographic glycan profiling with subsequent data alignment and statistical evaluation. 27891772 2 3 with profiling 490:498 arg1 evaluation 547:556 statistical evaluation 535:556 statistical evaluation 535:556 Commonly used analytical platforms for comparative relative quantitation of complex glycan samples include MALDI-TOF-MS or chromatographic glycan profiling with subsequent data alignment and statistical evaluation. 27891772 7 4 theme LC-MS 1361:1365 arg1 platform 1367:1374 The described twoplex 12 C6 /13 C6 aniline 2D LC-MS platform 1315:1374 The described twoplex 12 C6 /13 C6 aniline 2D LC-MS platform 1315:1374 The described twoplex 12 C6 /13 C6 aniline 2D LC-MS platform is ideally suited for differential glycomic analysis of structurally complex N-glycan pools due to combination and analysis of samples in a single LC-MS injection and the associated minimization in technical variation. 27891772 4 5 theme twoplex 800:806 arg1 oligosaccharides 838:853 twoplex isotopically labeled N-linked oligosaccharides 800:853 twoplex isotopically labeled N-linked oligosaccharides 800:853 Here, we introduce an offline 2D LC-MSE workflow for the fractionation and relative quantitation of twoplex isotopically labeled N-linked oligosaccharides using neutral 12 C6 and 13 C6 aniline (Δmass = 6 Da). 27891772 1 6 from proteins 334:341 arg1 characterization 289:304 the quantitative characterization 272:304 the quantitative characterization of N-glycans on therapeutic proteins 272:341 Quantitative glycomics represents an actively expanding research field ranging from the discovery of disease-associated glycan alterations to the quantitative characterization of N-glycans on therapeutic proteins. 27891772 6 7 attach released 1222:1229 arg1 proteins 1242:1249 serum proteins 1236:1249 serum proteins of patients diagnosed with various stages of colorectal cancer 1236:1312 The potential of the method was demonstrated for the differential analysis of structurally defined N-glycans released from serum proteins of patients diagnosed with various stages of colorectal cancer. 27891772 6 7 attach released 1222:1229 arg2 N-glycans 1212:1220 structurally defined N-glycans 1191:1220 structurally defined N-glycans released from serum proteins of patients diagnosed with various stages of colorectal cancer 1191:1312 The potential of the method was demonstrated for the differential analysis of structurally defined N-glycans released from serum proteins of patients diagnosed with various stages of colorectal cancer. 27891772 2 8 theme used 353:356 arg1 platforms 369:377 Commonly used analytical platforms 344:377 Commonly used analytical platforms for comparative relative quantitation of complex glycan samples 344:441 Commonly used analytical platforms for comparative relative quantitation of complex glycan samples include MALDI-TOF-MS or chromatographic glycan profiling with subsequent data alignment and statistical evaluation. 27891772 6 9 theme method 1134:1139 arg1 potential 1117:1125 The potential 1113:1125 The potential of the method 1113:1139 The potential of the method was demonstrated for the differential analysis of structurally defined N-glycans released from serum proteins of patients diagnosed with various stages of colorectal cancer. 27891772 7 10 theme single 1516:1521 arg1 injection 1529:1537 a single LC-MS injection 1514:1537 a single LC-MS injection 1514:1537 The described twoplex 12 C6 /13 C6 aniline 2D LC-MS platform is ideally suited for differential glycomic analysis of structurally complex N-glycan pools due to combination and analysis of samples in a single LC-MS injection and the associated minimization in technical variation. 27891772 7 11 theme aniline 1350:1356 arg1 platform 1367:1374 The described twoplex 12 C6 /13 C6 aniline 2D LC-MS platform 1315:1374 The described twoplex 12 C6 /13 C6 aniline 2D LC-MS platform 1315:1374 The described twoplex 12 C6 /13 C6 aniline 2D LC-MS platform is ideally suited for differential glycomic analysis of structurally complex N-glycan pools due to combination and analysis of samples in a single LC-MS injection and the associated minimization in technical variation. 27891772 1 12 theme glycan 250:255 arg1 alterations 257:267 disease-associated glycan alterations 231:267 disease-associated glycan alterations 231:267 Quantitative glycomics represents an actively expanding research field ranging from the discovery of disease-associated glycan alterations to the quantitative characterization of N-glycans on therapeutic proteins. 27891772 6 13 theme cancer 1307:1312 arg1 stages 1286:1291 various stages 1278:1291 various stages of colorectal cancer 1278:1312 The potential of the method was demonstrated for the differential analysis of structurally defined N-glycans released from serum proteins of patients diagnosed with various stages of colorectal cancer. 27891772 4 14 theme neutral 861:867 arg1 C6 872:873 neutral 12 C6 and 13 C6 aniline 861:891 C6 872:873 Here, we introduce an offline 2D LC-MSE workflow for the fractionation and relative quantitation of twoplex isotopically labeled N-linked oligosaccharides using neutral 12 C6 and 13 C6 aniline (Δmass = 6 Da). 27891772 1 15 theme Quantitative 130:141 arg1 glycomics 143:151 Quantitative glycomics 130:151 Quantitative glycomics 130:151 Quantitative glycomics represents an actively expanding research field ranging from the discovery of disease-associated glycan alterations to the quantitative characterization of N-glycans on therapeutic proteins. 27891772 7 16 theme associated 1547:1556 arg1 minimization 1558:1569 the associated minimization 1543:1569 the associated minimization in technical variation 1543:1592 The described twoplex 12 C6 /13 C6 aniline 2D LC-MS platform is ideally suited for differential glycomic analysis of structurally complex N-glycan pools due to combination and analysis of samples in a single LC-MS injection and the associated minimization in technical variation. 27891772 6 17 theme N-glycans 1212:1220 arg1 analysis 1179:1186 the differential analysis 1162:1186 the differential analysis of structurally defined N-glycans released from serum proteins of patients diagnosed with various stages of colorectal cancer 1162:1312 The potential of the method was demonstrated for the differential analysis of structurally defined N-glycans released from serum proteins of patients diagnosed with various stages of colorectal cancer. 27891772 4 18 theme labeled 821:827 arg1 oligosaccharides 838:853 twoplex isotopically labeled N-linked oligosaccharides 800:853 twoplex isotopically labeled N-linked oligosaccharides 800:853 Here, we introduce an offline 2D LC-MSE workflow for the fractionation and relative quantitation of twoplex isotopically labeled N-linked oligosaccharides using neutral 12 C6 and 13 C6 aniline (Δmass = 6 Da). 27891772 0 19 theme sialic 61:66 arg1 acid 68:71 linkage-specific sialic acid 44:71 linkage-specific sialic acid 44:71 Twoplex 12/13 C6 aniline stable isotope and linkage-specific sialic acid labeling 2D-LC-MS workflow for quantitative N-glycomics. 27891772 5 20 theme sialic 955:960 arg1 acids 962:966 sialic acids 955:966 sialic acids 955:966 Additional linkage-specific derivatization of sialic acids using 4-(4,6-dimethoxy-1,3,5-trizain-2-yl)-4-methylmorpholinium chloride offered simultaneous and advanced in-depth structural characterization. 27891772 4 21 dep = 900:900 arg1 Da 904:905 6 Da 902:905 6 Da 902:905 Here, we introduce an offline 2D LC-MSE workflow for the fractionation and relative quantitation of twoplex isotopically labeled N-linked oligosaccharides using neutral 12 C6 and 13 C6 aniline (Δmass = 6 Da). 27891772 4 22 theme oligosaccharides 838:853 arg1 fractionation 757:769 fractionation 757:769 fractionation 757:769 Here, we introduce an offline 2D LC-MSE workflow for the fractionation and relative quantitation of twoplex isotopically labeled N-linked oligosaccharides using neutral 12 C6 and 13 C6 aniline (Δmass = 6 Da). 27891772 4 22 theme oligosaccharides 838:853 arg1 quantitation 784:795 relative quantitation 775:795 relative quantitation of twoplex isotopically labeled N-linked oligosaccharides 775:853 Here, we introduce an offline 2D LC-MSE workflow for the fractionation and relative quantitation of twoplex isotopically labeled N-linked oligosaccharides using neutral 12 C6 and 13 C6 aniline (Δmass = 6 Da). 27891772 0 23 theme labeling 73:80 arg1 2D-LC-MS 82:89 Twoplex 12/13 C6 aniline stable isotope and linkage-specific sialic acid labeling 2D-LC-MS 0:89 Twoplex 12/13 C6 aniline stable isotope and linkage-specific sialic acid labeling 2D-LC-MS 0:89 Twoplex 12/13 C6 aniline stable isotope and linkage-specific sialic acid labeling 2D-LC-MS workflow for quantitative N-glycomics. 27891772 1 24 theme research 186:193 arg1 field 195:199 an actively expanding research field 164:199 an actively expanding research field ranging from the discovery of disease-associated glycan alterations to the quantitative characterization of N-glycans on therapeutic proteins 164:341 Quantitative glycomics represents an actively expanding research field ranging from the discovery of disease-associated glycan alterations to the quantitative characterization of N-glycans on therapeutic proteins. 27891772 2 25 theme subsequent 505:514 arg1 alignment 521:529 subsequent data alignment 505:529 subsequent data alignment 505:529 Commonly used analytical platforms for comparative relative quantitation of complex glycan samples include MALDI-TOF-MS or chromatographic glycan profiling with subsequent data alignment and statistical evaluation. 27891772 2 26 theme glycan 483:488 arg1 profiling 490:498 MALDI-TOF-MS or chromatographic glycan profiling 451:498 MALDI-TOF-MS or chromatographic glycan profiling with subsequent data alignment and statistical evaluation 451:556 Commonly used analytical platforms for comparative relative quantitation of complex glycan samples include MALDI-TOF-MS or chromatographic glycan profiling with subsequent data alignment and statistical evaluation. 27891772 0 27 theme quantitative 104:115 arg1 N-glycomics 117:127 quantitative N-glycomics 104:127 quantitative N-glycomics 104:127 Twoplex 12/13 C6 aniline stable isotope and linkage-specific sialic acid labeling 2D-LC-MS workflow for quantitative N-glycomics. 27891772 0 28 theme isotope 32:38 arg1 2D-LC-MS 82:89 Twoplex 12/13 C6 aniline stable isotope and linkage-specific sialic acid labeling 2D-LC-MS 0:89 Twoplex 12/13 C6 aniline stable isotope and linkage-specific sialic acid labeling 2D-LC-MS 0:89 Twoplex 12/13 C6 aniline stable isotope and linkage-specific sialic acid labeling 2D-LC-MS workflow for quantitative N-glycomics. 27891772 0 29 theme Twoplex 0:6 arg1 isotope 32:38 Twoplex 12/13 C6 aniline stable isotope 0:38 Twoplex 12/13 C6 aniline stable isotope 0:38 Twoplex 12/13 C6 aniline stable isotope and linkage-specific sialic acid labeling 2D-LC-MS workflow for quantitative N-glycomics. 27891772 1 30 theme therapeutic 322:332 arg1 proteins 334:341 therapeutic proteins 322:341 therapeutic proteins 322:341 Quantitative glycomics represents an actively expanding research field ranging from the discovery of disease-associated glycan alterations to the quantitative characterization of N-glycans on therapeutic proteins. 27891772 6 31 theme patients 1254:1261 arg1 proteins 1242:1249 serum proteins 1236:1249 serum proteins of patients diagnosed with various stages of colorectal cancer 1236:1312 The potential of the method was demonstrated for the differential analysis of structurally defined N-glycans released from serum proteins of patients diagnosed with various stages of colorectal cancer. 27891772 2 32 theme data 516:519 arg1 alignment 521:529 subsequent data alignment 505:529 subsequent data alignment 505:529 Commonly used analytical platforms for comparative relative quantitation of complex glycan samples include MALDI-TOF-MS or chromatographic glycan profiling with subsequent data alignment and statistical evaluation. 27891772 0 33 theme C6 14:15 arg1 isotope 32:38 Twoplex 12/13 C6 aniline stable isotope 0:38 Twoplex 12/13 C6 aniline stable isotope 0:38 Twoplex 12/13 C6 aniline stable isotope and linkage-specific sialic acid labeling 2D-LC-MS workflow for quantitative N-glycomics. 27891772 0 34 theme stable 25:30 arg1 isotope 32:38 Twoplex 12/13 C6 aniline stable isotope 0:38 Twoplex 12/13 C6 aniline stable isotope 0:38 Twoplex 12/13 C6 aniline stable isotope and linkage-specific sialic acid labeling 2D-LC-MS workflow for quantitative N-glycomics. 27891772 7 35 theme C6 1347:1348 arg1 platform 1367:1374 The described twoplex 12 C6 /13 C6 aniline 2D LC-MS platform 1315:1374 The described twoplex 12 C6 /13 C6 aniline 2D LC-MS platform 1315:1374 The described twoplex 12 C6 /13 C6 aniline 2D LC-MS platform is ideally suited for differential glycomic analysis of structurally complex N-glycan pools due to combination and analysis of samples in a single LC-MS injection and the associated minimization in technical variation. 27891772 4 36 dep fractionation 757:769 arg1 the 753:755 the 753:755 the 753:755 Here, we introduce an offline 2D LC-MSE workflow for the fractionation and relative quantitation of twoplex isotopically labeled N-linked oligosaccharides using neutral 12 C6 and 13 C6 aniline (Δmass = 6 Da). 27891772 7 37 from analysis 1491:1498 arg1 minimization 1558:1569 the associated minimization 1543:1569 the associated minimization in technical variation 1543:1592 The described twoplex 12 C6 /13 C6 aniline 2D LC-MS platform is ideally suited for differential glycomic analysis of structurally complex N-glycan pools due to combination and analysis of samples in a single LC-MS injection and the associated minimization in technical variation. 27891772 7 37 from analysis 1491:1498 arg1 injection 1529:1537 a single LC-MS injection 1514:1537 a single LC-MS injection 1514:1537 The described twoplex 12 C6 /13 C6 aniline 2D LC-MS platform is ideally suited for differential glycomic analysis of structurally complex N-glycan pools due to combination and analysis of samples in a single LC-MS injection and the associated minimization in technical variation. 27891772 3 38 theme run-to-run 598:607 arg1 variation 619:627 run-to-run technical variation 598:627 run-to-run technical variation 598:627 Limitations of such approaches include run-to-run technical variation and the potential introduction of subjectivity during data processing. 27891772 5 39 theme Additional 909:918 arg1 derivatization 937:950 Additional linkage-specific derivatization 909:950 Additional linkage-specific derivatization of sialic acids using 4-(4,6-dimethoxy-1,3,5-trizain-2-yl)-4-methylmorpholinium chloride 909:1039 Additional linkage-specific derivatization of sialic acids using 4-(4,6-dimethoxy-1,3,5-trizain-2-yl)-4-methylmorpholinium chloride offered simultaneous and advanced in-depth structural characterization. 27891772 7 40 from samples 1503:1509 arg1 minimization 1558:1569 the associated minimization 1543:1569 the associated minimization in technical variation 1543:1592 The described twoplex 12 C6 /13 C6 aniline 2D LC-MS platform is ideally suited for differential glycomic analysis of structurally complex N-glycan pools due to combination and analysis of samples in a single LC-MS injection and the associated minimization in technical variation. 27891772 7 40 from samples 1503:1509 arg1 injection 1529:1537 a single LC-MS injection 1514:1537 a single LC-MS injection 1514:1537 The described twoplex 12 C6 /13 C6 aniline 2D LC-MS platform is ideally suited for differential glycomic analysis of structurally complex N-glycan pools due to combination and analysis of samples in a single LC-MS injection and the associated minimization in technical variation. 27891772 2 41 theme relative 395:402 arg1 quantitation 404:415 comparative relative quantitation 383:415 comparative relative quantitation of complex glycan samples 383:441 Commonly used analytical platforms for comparative relative quantitation of complex glycan samples include MALDI-TOF-MS or chromatographic glycan profiling with subsequent data alignment and statistical evaluation. 27891772 1 42 theme alterations 257:267 arg1 discovery 218:226 the discovery 214:226 the discovery of disease-associated glycan alterations 214:267 Quantitative glycomics represents an actively expanding research field ranging from the discovery of disease-associated glycan alterations to the quantitative characterization of N-glycans on therapeutic proteins. 27891772 5 43 theme simultaneous 1049:1060 arg1 characterization 1095:1110 simultaneous and advanced in-depth structural characterization 1049:1110 simultaneous and advanced in-depth structural characterization 1049:1110 Additional linkage-specific derivatization of sialic acids using 4-(4,6-dimethoxy-1,3,5-trizain-2-yl)-4-methylmorpholinium chloride offered simultaneous and advanced in-depth structural characterization. 27891772 4 44 theme offline 722:728 arg1 workflow 740:747 an offline 2D LC-MSE workflow 719:747 an offline 2D LC-MSE workflow for the fractionation and relative quantitation of twoplex isotopically labeled N-linked oligosaccharides using neutral 12 C6 and 13 C6 aniline (Δmass = 6 Da) 719:906 Here, we introduce an offline 2D LC-MSE workflow for the fractionation and relative quantitation of twoplex isotopically labeled N-linked oligosaccharides using neutral 12 C6 and 13 C6 aniline (Δmass = 6 Da). 27891772 6 45 theme colorectal 1296:1305 arg1 cancer 1307:1312 colorectal cancer 1296:1312 colorectal cancer 1296:1312 The potential of the method was demonstrated for the differential analysis of structurally defined N-glycans released from serum proteins of patients diagnosed with various stages of colorectal cancer. 27891772 4 46 theme LC-MSE 733:738 arg1 workflow 740:747 an offline 2D LC-MSE workflow 719:747 an offline 2D LC-MSE workflow for the fractionation and relative quantitation of twoplex isotopically labeled N-linked oligosaccharides using neutral 12 C6 and 13 C6 aniline (Δmass = 6 Da) 719:906 Here, we introduce an offline 2D LC-MSE workflow for the fractionation and relative quantitation of twoplex isotopically labeled N-linked oligosaccharides using neutral 12 C6 and 13 C6 aniline (Δmass = 6 Da). 27891772 7 47 theme described 1319:1327 arg1 platform 1367:1374 The described twoplex 12 C6 /13 C6 aniline 2D LC-MS platform 1315:1374 The described twoplex 12 C6 /13 C6 aniline 2D LC-MS platform 1315:1374 The described twoplex 12 C6 /13 C6 aniline 2D LC-MS platform is ideally suited for differential glycomic analysis of structurally complex N-glycan pools due to combination and analysis of samples in a single LC-MS injection and the associated minimization in technical variation. 27891772 2 48 theme glycan 428:433 arg1 samples 435:441 complex glycan samples 420:441 complex glycan samples 420:441 Commonly used analytical platforms for comparative relative quantitation of complex glycan samples include MALDI-TOF-MS or chromatographic glycan profiling with subsequent data alignment and statistical evaluation. 27891772 5 49 theme structural 1084:1093 arg1 characterization 1095:1110 simultaneous and advanced in-depth structural characterization 1049:1110 simultaneous and advanced in-depth structural characterization 1049:1110 Additional linkage-specific derivatization of sialic acids using 4-(4,6-dimethoxy-1,3,5-trizain-2-yl)-4-methylmorpholinium chloride offered simultaneous and advanced in-depth structural characterization. 27891772 7 50 theme complex 1445:1451 arg1 pools 1462:1466 structurally complex N-glycan pools 1432:1466 structurally complex N-glycan pools due to combination and analysis of samples in a single LC-MS injection and the associated minimization in technical variation 1432:1592 The described twoplex 12 C6 /13 C6 aniline 2D LC-MS platform is ideally suited for differential glycomic analysis of structurally complex N-glycan pools due to combination and analysis of samples in a single LC-MS injection and the associated minimization in technical variation. 27891772 3 51 theme subjectivity 663:674 arg1 introduction 647:658 the potential introduction 633:658 the potential introduction of subjectivity during data processing 633:697 Limitations of such approaches include run-to-run technical variation and the potential introduction of subjectivity during data processing. 27891772 3 51 theme subjectivity 663:674 arg1 variation 619:627 run-to-run technical variation 598:627 run-to-run technical variation 598:627 Limitations of such approaches include run-to-run technical variation and the potential introduction of subjectivity during data processing. 27891772 1 52 theme N-glycans 309:317 arg1 characterization 289:304 the quantitative characterization 272:304 the quantitative characterization of N-glycans on therapeutic proteins 272:341 Quantitative glycomics represents an actively expanding research field ranging from the discovery of disease-associated glycan alterations to the quantitative characterization of N-glycans on therapeutic proteins. 27891772 7 53 theme 2D 1358:1359 arg1 platform 1367:1374 The described twoplex 12 C6 /13 C6 aniline 2D LC-MS platform 1315:1374 The described twoplex 12 C6 /13 C6 aniline 2D LC-MS platform 1315:1374 The described twoplex 12 C6 /13 C6 aniline 2D LC-MS platform is ideally suited for differential glycomic analysis of structurally complex N-glycan pools due to combination and analysis of samples in a single LC-MS injection and the associated minimization in technical variation. 27891772 5 54 theme 4,6-dimethoxy-1,3,5-trizain-2-yl 977:1008 arg1 chloride 1032:1039 4-(4,6-dimethoxy-1,3,5-trizain-2-yl)-4-methylmorpholinium chloride 974:1039 4-(4,6-dimethoxy-1,3,5-trizain-2-yl)-4-methylmorpholinium chloride 974:1039 Additional linkage-specific derivatization of sialic acids using 4-(4,6-dimethoxy-1,3,5-trizain-2-yl)-4-methylmorpholinium chloride offered simultaneous and advanced in-depth structural characterization. 27891772 7 55 theme C6 1340:1341 arg1 platform 1367:1374 The described twoplex 12 C6 /13 C6 aniline 2D LC-MS platform 1315:1374 The described twoplex 12 C6 /13 C6 aniline 2D LC-MS platform 1315:1374 The described twoplex 12 C6 /13 C6 aniline 2D LC-MS platform is ideally suited for differential glycomic analysis of structurally complex N-glycan pools due to combination and analysis of samples in a single LC-MS injection and the associated minimization in technical variation. 27891772 4 56 theme relative 775:782 arg1 quantitation 784:795 relative quantitation 775:795 relative quantitation of twoplex isotopically labeled N-linked oligosaccharides 775:853 Here, we introduce an offline 2D LC-MSE workflow for the fractionation and relative quantitation of twoplex isotopically labeled N-linked oligosaccharides using neutral 12 C6 and 13 C6 aniline (Δmass = 6 Da). 27891772 7 57 theme glycomic 1411:1418 arg1 analysis 1420:1427 differential glycomic analysis 1398:1427 differential glycomic analysis of structurally complex N-glycan pools due to combination and analysis of samples in a single LC-MS injection and the associated minimization in technical variation 1398:1592 The described twoplex 12 C6 /13 C6 aniline 2D LC-MS platform is ideally suited for differential glycomic analysis of structurally complex N-glycan pools due to combination and analysis of samples in a single LC-MS injection and the associated minimization in technical variation. 27891772 5 58 theme -4-methylmorpholinium 1010:1030 arg1 chloride 1032:1039 4-(4,6-dimethoxy-1,3,5-trizain-2-yl)-4-methylmorpholinium chloride 974:1039 4-(4,6-dimethoxy-1,3,5-trizain-2-yl)-4-methylmorpholinium chloride 974:1039 Additional linkage-specific derivatization of sialic acids using 4-(4,6-dimethoxy-1,3,5-trizain-2-yl)-4-methylmorpholinium chloride offered simultaneous and advanced in-depth structural characterization. 27891772 7 59 from combination 1475:1485 arg1 minimization 1558:1569 the associated minimization 1543:1569 the associated minimization in technical variation 1543:1592 The described twoplex 12 C6 /13 C6 aniline 2D LC-MS platform is ideally suited for differential glycomic analysis of structurally complex N-glycan pools due to combination and analysis of samples in a single LC-MS injection and the associated minimization in technical variation. 27891772 7 59 from combination 1475:1485 arg1 injection 1529:1537 a single LC-MS injection 1514:1537 a single LC-MS injection 1514:1537 The described twoplex 12 C6 /13 C6 aniline 2D LC-MS platform is ideally suited for differential glycomic analysis of structurally complex N-glycan pools due to combination and analysis of samples in a single LC-MS injection and the associated minimization in technical variation. 27891772 4 60 link N-linked 829:836 arg1 oligosaccharides 838:853 twoplex isotopically labeled N-linked oligosaccharides 800:853 twoplex isotopically labeled N-linked oligosaccharides 800:853 Here, we introduce an offline 2D LC-MSE workflow for the fractionation and relative quantitation of twoplex isotopically labeled N-linked oligosaccharides using neutral 12 C6 and 13 C6 aniline (Δmass = 6 Da). 27891772 1 61 from N-glycans 309:317 arg1 proteins 334:341 therapeutic proteins 322:341 therapeutic proteins 322:341 Quantitative glycomics represents an actively expanding research field ranging from the discovery of disease-associated glycan alterations to the quantitative characterization of N-glycans on therapeutic proteins. 27891772 2 62 theme analytical 358:367 arg1 platforms 369:377 Commonly used analytical platforms 344:377 Commonly used analytical platforms for comparative relative quantitation of complex glycan samples 344:441 Commonly used analytical platforms for comparative relative quantitation of complex glycan samples include MALDI-TOF-MS or chromatographic glycan profiling with subsequent data alignment and statistical evaluation. 27891772 5 63 theme acids 962:966 arg1 derivatization 937:950 Additional linkage-specific derivatization 909:950 Additional linkage-specific derivatization of sialic acids using 4-(4,6-dimethoxy-1,3,5-trizain-2-yl)-4-methylmorpholinium chloride 909:1039 Additional linkage-specific derivatization of sialic acids using 4-(4,6-dimethoxy-1,3,5-trizain-2-yl)-4-methylmorpholinium chloride offered simultaneous and advanced in-depth structural characterization. 27891772 5 64 theme advanced 1066:1073 arg1 characterization 1095:1110 simultaneous and advanced in-depth structural characterization 1049:1110 simultaneous and advanced in-depth structural characterization 1049:1110 Additional linkage-specific derivatization of sialic acids using 4-(4,6-dimethoxy-1,3,5-trizain-2-yl)-4-methylmorpholinium chloride offered simultaneous and advanced in-depth structural characterization. 27891772 1 65 from characterization 289:304 arg1 proteins 334:341 therapeutic proteins 322:341 therapeutic proteins 322:341 Quantitative glycomics represents an actively expanding research field ranging from the discovery of disease-associated glycan alterations to the quantitative characterization of N-glycans on therapeutic proteins. 27891772 1 66 theme disease-associated 231:248 arg1 alterations 257:267 disease-associated glycan alterations 231:267 disease-associated glycan alterations 231:267 Quantitative glycomics represents an actively expanding research field ranging from the discovery of disease-associated glycan alterations to the quantitative characterization of N-glycans on therapeutic proteins. 27891772 5 67 theme in-depth 1075:1082 arg1 characterization 1095:1110 simultaneous and advanced in-depth structural characterization 1049:1110 simultaneous and advanced in-depth structural characterization 1049:1110 Additional linkage-specific derivatization of sialic acids using 4-(4,6-dimethoxy-1,3,5-trizain-2-yl)-4-methylmorpholinium chloride offered simultaneous and advanced in-depth structural characterization. 27891772 7 68 theme technical 1574:1582 arg1 variation 1584:1592 technical variation 1574:1592 technical variation 1574:1592 The described twoplex 12 C6 /13 C6 aniline 2D LC-MS platform is ideally suited for differential glycomic analysis of structurally complex N-glycan pools due to combination and analysis of samples in a single LC-MS injection and the associated minimization in technical variation. 27891772 7 69 theme pools 1462:1466 arg1 analysis 1420:1427 differential glycomic analysis 1398:1427 differential glycomic analysis of structurally complex N-glycan pools due to combination and analysis of samples in a single LC-MS injection and the associated minimization in technical variation 1398:1592 The described twoplex 12 C6 /13 C6 aniline 2D LC-MS platform is ideally suited for differential glycomic analysis of structurally complex N-glycan pools due to combination and analysis of samples in a single LC-MS injection and the associated minimization in technical variation. 27891772 3 70 theme data 683:686 arg1 processing 688:697 data processing 683:697 data processing 683:697 Limitations of such approaches include run-to-run technical variation and the potential introduction of subjectivity during data processing. 27891772 3 71 theme approaches 579:588 arg1 Limitations 559:569 Limitations 559:569 Limitations of such approaches 559:588 Limitations of such approaches include run-to-run technical variation and the potential introduction of subjectivity during data processing. 27891772 0 72 theme acid 68:71 arg1 2D-LC-MS 82:89 Twoplex 12/13 C6 aniline stable isotope and linkage-specific sialic acid labeling 2D-LC-MS 0:89 Twoplex 12/13 C6 aniline stable isotope and linkage-specific sialic acid labeling 2D-LC-MS 0:89 Twoplex 12/13 C6 aniline stable isotope and linkage-specific sialic acid labeling 2D-LC-MS workflow for quantitative N-glycomics. 27891772 6 73 theme defined 1204:1210 arg1 N-glycans 1212:1220 structurally defined N-glycans 1191:1220 structurally defined N-glycans released from serum proteins of patients diagnosed with various stages of colorectal cancer 1191:1312 The potential of the method was demonstrated for the differential analysis of structurally defined N-glycans released from serum proteins of patients diagnosed with various stages of colorectal cancer. 27891772 7 74 theme differential 1398:1409 arg1 analysis 1420:1427 differential glycomic analysis 1398:1427 differential glycomic analysis of structurally complex N-glycan pools due to combination and analysis of samples in a single LC-MS injection and the associated minimization in technical variation 1398:1592 The described twoplex 12 C6 /13 C6 aniline 2D LC-MS platform is ideally suited for differential glycomic analysis of structurally complex N-glycan pools due to combination and analysis of samples in a single LC-MS injection and the associated minimization in technical variation. 27891772 1 75 theme expanding 176:184 arg1 field 195:199 an actively expanding research field 164:199 an actively expanding research field ranging from the discovery of disease-associated glycan alterations to the quantitative characterization of N-glycans on therapeutic proteins 164:341 Quantitative glycomics represents an actively expanding research field ranging from the discovery of disease-associated glycan alterations to the quantitative characterization of N-glycans on therapeutic proteins. 27891772 4 76 theme N-linked 829:836 arg1 oligosaccharides 838:853 twoplex isotopically labeled N-linked oligosaccharides 800:853 twoplex isotopically labeled N-linked oligosaccharides 800:853 Here, we introduce an offline 2D LC-MSE workflow for the fractionation and relative quantitation of twoplex isotopically labeled N-linked oligosaccharides using neutral 12 C6 and 13 C6 aniline (Δmass = 6 Da). 27891772 6 77 theme differential 1166:1177 arg1 analysis 1179:1186 the differential analysis 1162:1186 the differential analysis of structurally defined N-glycans released from serum proteins of patients diagnosed with various stages of colorectal cancer 1162:1312 The potential of the method was demonstrated for the differential analysis of structurally defined N-glycans released from serum proteins of patients diagnosed with various stages of colorectal cancer. 27891772 2 78 theme comparative 383:393 arg1 quantitation 404:415 comparative relative quantitation 383:415 comparative relative quantitation of complex glycan samples 383:441 Commonly used analytical platforms for comparative relative quantitation of complex glycan samples include MALDI-TOF-MS or chromatographic glycan profiling with subsequent data alignment and statistical evaluation. 27891772 7 79 theme LC-MS 1523:1527 arg1 injection 1529:1537 a single LC-MS injection 1514:1537 a single LC-MS injection 1514:1537 The described twoplex 12 C6 /13 C6 aniline 2D LC-MS platform is ideally suited for differential glycomic analysis of structurally complex N-glycan pools due to combination and analysis of samples in a single LC-MS injection and the associated minimization in technical variation. 27891772 4 80 theme = 900:900 arg1 Δmass 894:898 Δmass 894:898 Δmass = 6 Da 894:905 Here, we introduce an offline 2D LC-MSE workflow for the fractionation and relative quantitation of twoplex isotopically labeled N-linked oligosaccharides using neutral 12 C6 and 13 C6 aniline (Δmass = 6 Da). 27891772 2 81 theme chromatographic 467:481 arg1 profiling 490:498 MALDI-TOF-MS or chromatographic glycan profiling 451:498 MALDI-TOF-MS or chromatographic glycan profiling with subsequent data alignment and statistical evaluation 451:556 Commonly used analytical platforms for comparative relative quantitation of complex glycan samples include MALDI-TOF-MS or chromatographic glycan profiling with subsequent data alignment and statistical evaluation. 27891772 5 82 theme linkage-specific 920:935 arg1 derivatization 937:950 Additional linkage-specific derivatization 909:950 Additional linkage-specific derivatization of sialic acids using 4-(4,6-dimethoxy-1,3,5-trizain-2-yl)-4-methylmorpholinium chloride 909:1039 Additional linkage-specific derivatization of sialic acids using 4-(4,6-dimethoxy-1,3,5-trizain-2-yl)-4-methylmorpholinium chloride offered simultaneous and advanced in-depth structural characterization. 27891772 4 83 dep C6 872:873 arg1 Δmass 894:898 Δmass 894:898 Δmass = 6 Da 894:905 Here, we introduce an offline 2D LC-MSE workflow for the fractionation and relative quantitation of twoplex isotopically labeled N-linked oligosaccharides using neutral 12 C6 and 13 C6 aniline (Δmass = 6 Da). 27891772 7 84 from minimization 1558:1569 arg1 variation 1584:1592 technical variation 1574:1592 technical variation 1574:1592 The described twoplex 12 C6 /13 C6 aniline 2D LC-MS platform is ideally suited for differential glycomic analysis of structurally complex N-glycan pools due to combination and analysis of samples in a single LC-MS injection and the associated minimization in technical variation. 27891772 7 84 from minimization 1558:1569 arg1 analysis 1491:1498 analysis 1491:1498 analysis 1491:1498 The described twoplex 12 C6 /13 C6 aniline 2D LC-MS platform is ideally suited for differential glycomic analysis of structurally complex N-glycan pools due to combination and analysis of samples in a single LC-MS injection and the associated minimization in technical variation. 27891772 7 84 from minimization 1558:1569 arg1 combination 1475:1485 combination 1475:1485 combination 1475:1485 The described twoplex 12 C6 /13 C6 aniline 2D LC-MS platform is ideally suited for differential glycomic analysis of structurally complex N-glycan pools due to combination and analysis of samples in a single LC-MS injection and the associated minimization in technical variation. 27891772 2 85 theme statistical 535:545 arg1 evaluation 547:556 statistical evaluation 535:556 statistical evaluation 535:556 Commonly used analytical platforms for comparative relative quantitation of complex glycan samples include MALDI-TOF-MS or chromatographic glycan profiling with subsequent data alignment and statistical evaluation. 27891772 2 86 theme MALDI-TOF-MS 451:462 arg1 profiling 490:498 MALDI-TOF-MS or chromatographic glycan profiling 451:498 MALDI-TOF-MS or chromatographic glycan profiling with subsequent data alignment and statistical evaluation 451:556 Commonly used analytical platforms for comparative relative quantitation of complex glycan samples include MALDI-TOF-MS or chromatographic glycan profiling with subsequent data alignment and statistical evaluation. 27891772 0 87 theme aniline 17:23 arg1 isotope 32:38 Twoplex 12/13 C6 aniline stable isotope 0:38 Twoplex 12/13 C6 aniline stable isotope 0:38 Twoplex 12/13 C6 aniline stable isotope and linkage-specific sialic acid labeling 2D-LC-MS workflow for quantitative N-glycomics. 27891772 7 88 theme samples 1503:1509 arg1 analysis 1491:1498 analysis 1491:1498 analysis 1491:1498 The described twoplex 12 C6 /13 C6 aniline 2D LC-MS platform is ideally suited for differential glycomic analysis of structurally complex N-glycan pools due to combination and analysis of samples in a single LC-MS injection and the associated minimization in technical variation. 27891772 7 88 theme samples 1503:1509 arg1 combination 1475:1485 combination 1475:1485 combination 1475:1485 The described twoplex 12 C6 /13 C6 aniline 2D LC-MS platform is ideally suited for differential glycomic analysis of structurally complex N-glycan pools due to combination and analysis of samples in a single LC-MS injection and the associated minimization in technical variation. 27891772 4 89 theme C6 882:883 arg1 aniline 885:891 neutral 12 C6 and 13 C6 aniline 861:891 aniline 885:891 Here, we introduce an offline 2D LC-MSE workflow for the fractionation and relative quantitation of twoplex isotopically labeled N-linked oligosaccharides using neutral 12 C6 and 13 C6 aniline (Δmass = 6 Da). 27891772 3 90 theme such 574:577 arg1 approaches 579:588 such approaches 574:588 such approaches 574:588 Limitations of such approaches include run-to-run technical variation and the potential introduction of subjectivity during data processing. 27891772 7 91 theme /13 1343:1345 arg1 platform 1367:1374 The described twoplex 12 C6 /13 C6 aniline 2D LC-MS platform 1315:1374 The described twoplex 12 C6 /13 C6 aniline 2D LC-MS platform 1315:1374 The described twoplex 12 C6 /13 C6 aniline 2D LC-MS platform is ideally suited for differential glycomic analysis of structurally complex N-glycan pools due to combination and analysis of samples in a single LC-MS injection and the associated minimization in technical variation. 27891772 6 92 theme serum 1236:1240 arg1 proteins 1242:1249 serum proteins 1236:1249 serum proteins of patients diagnosed with various stages of colorectal cancer 1236:1312 The potential of the method was demonstrated for the differential analysis of structurally defined N-glycans released from serum proteins of patients diagnosed with various stages of colorectal cancer. 27891772 6 93 theme various 1278:1284 arg1 stages 1286:1291 various stages 1278:1291 various stages of colorectal cancer 1278:1312 The potential of the method was demonstrated for the differential analysis of structurally defined N-glycans released from serum proteins of patients diagnosed with various stages of colorectal cancer. 27891772 0 94 theme linkage-specific 44:59 arg1 acid 68:71 linkage-specific sialic acid 44:71 linkage-specific sialic acid 44:71 Twoplex 12/13 C6 aniline stable isotope and linkage-specific sialic acid labeling 2D-LC-MS workflow for quantitative N-glycomics. 27891772 2 95 theme samples 435:441 arg1 quantitation 404:415 comparative relative quantitation 383:415 comparative relative quantitation of complex glycan samples 383:441 Commonly used analytical platforms for comparative relative quantitation of complex glycan samples include MALDI-TOF-MS or chromatographic glycan profiling with subsequent data alignment and statistical evaluation. 27891772 3 96 theme technical 609:617 arg1 variation 619:627 run-to-run technical variation 598:627 run-to-run technical variation 598:627 Limitations of such approaches include run-to-run technical variation and the potential introduction of subjectivity during data processing. 27891772 7 97 theme due 1468:1470 arg1 pools 1462:1466 structurally complex N-glycan pools 1432:1466 structurally complex N-glycan pools due to combination and analysis of samples in a single LC-MS injection and the associated minimization in technical variation 1432:1592 The described twoplex 12 C6 /13 C6 aniline 2D LC-MS platform is ideally suited for differential glycomic analysis of structurally complex N-glycan pools due to combination and analysis of samples in a single LC-MS injection and the associated minimization in technical variation. 27891772 4 98 theme 2D 730:731 arg1 workflow 740:747 an offline 2D LC-MSE workflow 719:747 an offline 2D LC-MSE workflow for the fractionation and relative quantitation of twoplex isotopically labeled N-linked oligosaccharides using neutral 12 C6 and 13 C6 aniline (Δmass = 6 Da) 719:906 Here, we introduce an offline 2D LC-MSE workflow for the fractionation and relative quantitation of twoplex isotopically labeled N-linked oligosaccharides using neutral 12 C6 and 13 C6 aniline (Δmass = 6 Da). 27891772 3 99 theme potential 637:645 arg1 introduction 647:658 the potential introduction 633:658 the potential introduction of subjectivity during data processing 633:697 Limitations of such approaches include run-to-run technical variation and the potential introduction of subjectivity during data processing. 27891772 7 100 theme N-glycan 1453:1460 arg1 pools 1462:1466 structurally complex N-glycan pools 1432:1466 structurally complex N-glycan pools due to combination and analysis of samples in a single LC-MS injection and the associated minimization in technical variation 1432:1592 The described twoplex 12 C6 /13 C6 aniline 2D LC-MS platform is ideally suited for differential glycomic analysis of structurally complex N-glycan pools due to combination and analysis of samples in a single LC-MS injection and the associated minimization in technical variation. 27891772 0 101 theme 12/13 8:12 arg1 isotope 32:38 Twoplex 12/13 C6 aniline stable isotope 0:38 Twoplex 12/13 C6 aniline stable isotope 0:38 Twoplex 12/13 C6 aniline stable isotope and linkage-specific sialic acid labeling 2D-LC-MS workflow for quantitative N-glycomics. 27891772 1 102 theme quantitative 276:287 arg1 characterization 289:304 the quantitative characterization 272:304 the quantitative characterization of N-glycans on therapeutic proteins 272:341 Quantitative glycomics represents an actively expanding research field ranging from the discovery of disease-associated glycan alterations to the quantitative characterization of N-glycans on therapeutic proteins. 27810882 5 0 theme N-linked 1108:1115 arg1 glycoproteins 1117:1129 N-linked glycoproteins 1108:1129 N-linked glycoproteins 1108:1129 Specificities of the adhesin (FimH) also varied between the isolates: most bound to α-(1-3) mannan and yeast extracts as expected, but some recognised β-(1-4)-mannans and N-linked glycoproteins from plants, and T1F from two of the isolates mediated binding to plant roots. 27810882 5 1 theme yeast 1040:1044 arg1 extracts 1046:1053 yeast extracts 1040:1053 yeast extracts 1040:1053 Specificities of the adhesin (FimH) also varied between the isolates: most bound to α-(1-3) mannan and yeast extracts as expected, but some recognised β-(1-4)-mannans and N-linked glycoproteins from plants, and T1F from two of the isolates mediated binding to plant roots. 27810882 3 2 theme environmental 492:504 arg1 isolates 525:532 136 environmental and animal E. coli isolates 488:532 136 environmental and animal E. coli isolates that express T1F at 37°C 488:557 Analysis of a group of 136 environmental and animal E. coli isolates that express T1F at 37°C showed that 28% are also capable of expression at 20°C, in a phase variable manner. 27810882 0 3 theme fimbriae 77:84 arg1 thermoregulation 10:25 Alternate thermoregulation 0:25 Alternate thermoregulation 0:25 Alternate thermoregulation and functional binding of Escherichia coli type 1 fimbriae in environmental and animal isolates. 27810882 0 3 theme fimbriae 77:84 arg1 binding 42:48 functional binding 31:48 functional binding 31:48 Alternate thermoregulation and functional binding of Escherichia coli type 1 fimbriae in environmental and animal isolates. 27810882 0 4 from thermoregulation 10:25 arg1 isolates 114:121 environmental and animal isolates 89:121 environmental and animal isolates 89:121 Alternate thermoregulation and functional binding of Escherichia coli type 1 fimbriae in environmental and animal isolates. 27810882 4 5 theme heterogeneous 647:659 arg1 proportions 661:671 The heterogeneous proportions 643:671 The heterogeneous proportions 643:671 The heterogeneous proportions varied widely, and although growth temperature impacted the total proportion expressing T1F, there was no direct correlation between growth at 37°C and 20°C, indicative of differences in thermoregulation of the genetic switch (fimS) that controls phase variation. 27810882 4 6 theme fimS 900:903 arg1 thermoregulation 860:875 thermoregulation 860:875 thermoregulation of the genetic switch (fimS) that controls phase variation 860:934 The heterogeneous proportions varied widely, and although growth temperature impacted the total proportion expressing T1F, there was no direct correlation between growth at 37°C and 20°C, indicative of differences in thermoregulation of the genetic switch (fimS) that controls phase variation. 27810882 5 7 link N-linked 1108:1115 arg1 glycoproteins 1117:1129 N-linked glycoproteins 1108:1129 N-linked glycoproteins 1108:1129 Specificities of the adhesin (FimH) also varied between the isolates: most bound to α-(1-3) mannan and yeast extracts as expected, but some recognised β-(1-4)-mannans and N-linked glycoproteins from plants, and T1F from two of the isolates mediated binding to plant roots. 27810882 4 8 theme total 733:737 arg1 proportion 739:748 the total proportion 729:748 the total proportion expressing T1F 729:763 The heterogeneous proportions varied widely, and although growth temperature impacted the total proportion expressing T1F, there was no direct correlation between growth at 37°C and 20°C, indicative of differences in thermoregulation of the genetic switch (fimS) that controls phase variation. 27810882 1 9 theme mannosylated 253:264 arg1 tissue 271:276 mannosylated host tissue 253:276 mannosylated host tissue 253:276 Type 1 fimbriae (T1F) are well characterised cell surface organelles expressed by Escherichia coli and required for adherence to mannosylated host tissue. 27810882 0 10 theme environmental 89:101 arg1 isolates 114:121 environmental and animal isolates 89:121 environmental and animal isolates 89:121 Alternate thermoregulation and functional binding of Escherichia coli type 1 fimbriae in environmental and animal isolates. 27810882 5 11 from two 1157:1159 arg1 -mannans 1095:1102 some recognised β-(1-4)-mannans 1072:1102 some recognised β-(1-4)-mannans 1072:1102 Specificities of the adhesin (FimH) also varied between the isolates: most bound to α-(1-3) mannan and yeast extracts as expected, but some recognised β-(1-4)-mannans and N-linked glycoproteins from plants, and T1F from two of the isolates mediated binding to plant roots. 27810882 5 11 from two 1157:1159 arg1 glycoproteins 1117:1129 N-linked glycoproteins 1108:1129 N-linked glycoproteins 1108:1129 Specificities of the adhesin (FimH) also varied between the isolates: most bound to α-(1-3) mannan and yeast extracts as expected, but some recognised β-(1-4)-mannans and N-linked glycoproteins from plants, and T1F from two of the isolates mediated binding to plant roots. 27810882 1 12 theme host 266:269 arg1 tissue 271:276 mannosylated host tissue 253:276 mannosylated host tissue 253:276 Type 1 fimbriae (T1F) are well characterised cell surface organelles expressed by Escherichia coli and required for adherence to mannosylated host tissue. 27810882 3 13 theme coli 520:523 arg1 isolates 525:532 136 environmental and animal E. coli isolates 488:532 136 environmental and animal E. coli isolates that express T1F at 37°C 488:557 Analysis of a group of 136 environmental and animal E. coli isolates that express T1F at 37°C showed that 28% are also capable of expression at 20°C, in a phase variable manner. 27810882 3 14 from capable 584:590 arg1 manner 635:640 a phase variable manner 618:640 a phase variable manner 618:640 Analysis of a group of 136 environmental and animal E. coli isolates that express T1F at 37°C showed that 28% are also capable of expression at 20°C, in a phase variable manner. 27810882 5 15 theme α- 1021:1022 arg1 mannan 1029:1034 α-(1-3) mannan 1021:1034 α-(1-3) mannan 1021:1034 Specificities of the adhesin (FimH) also varied between the isolates: most bound to α-(1-3) mannan and yeast extracts as expected, but some recognised β-(1-4)-mannans and N-linked glycoproteins from plants, and T1F from two of the isolates mediated binding to plant roots. 27810882 0 16 theme animal 107:112 arg1 isolates 114:121 environmental and animal isolates 89:121 environmental and animal isolates 89:121 Alternate thermoregulation and functional binding of Escherichia coli type 1 fimbriae in environmental and animal isolates. 27810882 3 17 theme isolates 525:532 arg1 group 479:483 a group 477:483 a group of 136 environmental and animal E. coli isolates that express T1F at 37°C 477:557 Analysis of a group of 136 environmental and animal E. coli isolates that express T1F at 37°C showed that 28% are also capable of expression at 20°C, in a phase variable manner. 27810882 3 17 theme isolates 525:532 arg1 isolates 525:532 136 environmental and animal E. coli isolates 488:532 136 environmental and animal E. coli isolates that express T1F at 37°C 488:557 Analysis of a group of 136 environmental and animal E. coli isolates that express T1F at 37°C showed that 28% are also capable of expression at 20°C, in a phase variable manner. 27810882 1 18 theme characterised 155:167 arg1 fimbriae 131:138 Type 1 fimbriae 124:138 Type 1 fimbriae (T1F) 124:144 Type 1 fimbriae (T1F) are well characterised cell surface organelles expressed by Escherichia coli and required for adherence to mannosylated host tissue. 27810882 1 18 theme characterised 155:167 arg1 organelles 182:191 well characterised cell surface organelles 150:191 well characterised cell surface organelles expressed by Escherichia coli and required for adherence to mannosylated host tissue 150:276 Type 1 fimbriae (T1F) are well characterised cell surface organelles expressed by Escherichia coli and required for adherence to mannosylated host tissue. 27810882 2 19 theme submammalian 438:449 arg1 temperatures 451:462 submammalian temperatures 438:462 submammalian temperatures 438:462 They satisfy molecular Koch's postulates as a virulence determinant and a host-adapted role has been reinforced by reports that T1F expression is repressed at submammalian temperatures. 27810882 0 20 from binding 42:48 arg1 isolates 114:121 environmental and animal isolates 89:121 environmental and animal isolates 89:121 Alternate thermoregulation and functional binding of Escherichia coli type 1 fimbriae in environmental and animal isolates. 27810882 5 21 theme adhesin 958:964 arg1 Specificities 937:949 Specificities 937:949 Specificities of the adhesin (FimH) 937:971 Specificities of the adhesin (FimH) also varied between the isolates: most bound to α-(1-3) mannan and yeast extracts as expected, but some recognised β-(1-4)-mannans and N-linked glycoproteins from plants, and T1F from two of the isolates mediated binding to plant roots. 27810882 4 22 theme growth 701:706 arg1 temperature 708:718 growth temperature 701:718 growth temperature 701:718 The heterogeneous proportions varied widely, and although growth temperature impacted the total proportion expressing T1F, there was no direct correlation between growth at 37°C and 20°C, indicative of differences in thermoregulation of the genetic switch (fimS) that controls phase variation. 27810882 1 23 theme cell 169:172 arg1 fimbriae 131:138 Type 1 fimbriae 124:138 Type 1 fimbriae (T1F) 124:144 Type 1 fimbriae (T1F) are well characterised cell surface organelles expressed by Escherichia coli and required for adherence to mannosylated host tissue. 27810882 1 23 theme cell 169:172 arg1 organelles 182:191 well characterised cell surface organelles 150:191 well characterised cell surface organelles expressed by Escherichia coli and required for adherence to mannosylated host tissue 150:276 Type 1 fimbriae (T1F) are well characterised cell surface organelles expressed by Escherichia coli and required for adherence to mannosylated host tissue. 27810882 0 24 theme Alternate 0:8 arg1 thermoregulation 10:25 Alternate thermoregulation 0:25 Alternate thermoregulation 0:25 Alternate thermoregulation and functional binding of Escherichia coli type 1 fimbriae in environmental and animal isolates. 27810882 5 25 theme recognised 1077:1086 arg1 -mannans 1095:1102 some recognised β-(1-4)-mannans 1072:1102 some recognised β-(1-4)-mannans 1072:1102 Specificities of the adhesin (FimH) also varied between the isolates: most bound to α-(1-3) mannan and yeast extracts as expected, but some recognised β-(1-4)-mannans and N-linked glycoproteins from plants, and T1F from two of the isolates mediated binding to plant roots. 27810882 6 26 theme alternative 1404:1414 arg1 hosts 1416:1420 alternative hosts 1404:1420 alternative hosts 1404:1420 The results expand our view of a well-described adherence factor to show alternative expression profiles and adhesin specificities, which in turn may confer an advantage for certain isolates in alternative hosts and habitats. 27810882 1 27 theme surface 174:180 arg1 fimbriae 131:138 Type 1 fimbriae 124:138 Type 1 fimbriae (T1F) 124:144 Type 1 fimbriae (T1F) are well characterised cell surface organelles expressed by Escherichia coli and required for adherence to mannosylated host tissue. 27810882 1 27 theme surface 174:180 arg1 organelles 182:191 well characterised cell surface organelles 150:191 well characterised cell surface organelles expressed by Escherichia coli and required for adherence to mannosylated host tissue 150:276 Type 1 fimbriae (T1F) are well characterised cell surface organelles expressed by Escherichia coli and required for adherence to mannosylated host tissue. 27810882 0 28 theme functional 31:40 arg1 binding 42:48 functional binding 31:48 functional binding 31:48 Alternate thermoregulation and functional binding of Escherichia coli type 1 fimbriae in environmental and animal isolates. 27810882 5 29 theme β- 1088:1089 arg1 -mannans 1095:1102 some recognised β-(1-4)-mannans 1072:1102 some recognised β-(1-4)-mannans 1072:1102 Specificities of the adhesin (FimH) also varied between the isolates: most bound to α-(1-3) mannan and yeast extracts as expected, but some recognised β-(1-4)-mannans and N-linked glycoproteins from plants, and T1F from two of the isolates mediated binding to plant roots. 27810882 4 30 theme genetic 884:890 arg1 fimS 900:903 the genetic switch (fimS) 880:904 the genetic switch (fimS) that controls phase variation 880:934 The heterogeneous proportions varied widely, and although growth temperature impacted the total proportion expressing T1F, there was no direct correlation between growth at 37°C and 20°C, indicative of differences in thermoregulation of the genetic switch (fimS) that controls phase variation. 27810882 1 31 gly mannosylated 253:264 arg1 tissue 271:276 mannosylated host tissue 253:276 mannosylated host tissue 253:276 Type 1 fimbriae (T1F) are well characterised cell surface organelles expressed by Escherichia coli and required for adherence to mannosylated host tissue. 27810882 6 32 theme well-described 1243:1256 arg1 factor 1268:1273 a well-described adherence factor 1241:1273 a well-described adherence factor 1241:1273 The results expand our view of a well-described adherence factor to show alternative expression profiles and adhesin specificities, which in turn may confer an advantage for certain isolates in alternative hosts and habitats. 27810882 2 33 theme molecular 292:300 arg1 Koch 302:305 molecular Koch 292:305 molecular Koch's postulates as a virulence determinant 292:345 They satisfy molecular Koch's postulates as a virulence determinant and a host-adapted role has been reinforced by reports that T1F expression is repressed at submammalian temperatures. 27810882 5 34 theme plant 1197:1201 arg1 roots 1203:1207 plant roots 1197:1207 plant roots 1197:1207 Specificities of the adhesin (FimH) also varied between the isolates: most bound to α-(1-3) mannan and yeast extracts as expected, but some recognised β-(1-4)-mannans and N-linked glycoproteins from plants, and T1F from two of the isolates mediated binding to plant roots. 27810882 2 35 theme T1F 407:409 arg1 expression 411:420 T1F expression 407:420 T1F expression 407:420 They satisfy molecular Koch's postulates as a virulence determinant and a host-adapted role has been reinforced by reports that T1F expression is repressed at submammalian temperatures. 27810882 2 36 theme virulence 325:333 arg1 determinant 335:345 a virulence determinant 323:345 a virulence determinant 323:345 They satisfy molecular Koch's postulates as a virulence determinant and a host-adapted role has been reinforced by reports that T1F expression is repressed at submammalian temperatures. 27810882 3 37 from manner 635:640 arg1 capable 584:590 capable 584:590 capable 584:590 Analysis of a group of 136 environmental and animal E. coli isolates that express T1F at 37°C showed that 28% are also capable of expression at 20°C, in a phase variable manner. 27810882 4 38 theme direct 779:784 arg1 correlation 786:796 no direct correlation 776:796 no direct correlation between growth 776:811 The heterogeneous proportions varied widely, and although growth temperature impacted the total proportion expressing T1F, there was no direct correlation between growth at 37°C and 20°C, indicative of differences in thermoregulation of the genetic switch (fimS) that controls phase variation. 27810882 6 39 theme certain 1384:1390 arg1 isolates 1392:1399 certain isolates 1384:1399 certain isolates 1384:1399 The results expand our view of a well-described adherence factor to show alternative expression profiles and adhesin specificities, which in turn may confer an advantage for certain isolates in alternative hosts and habitats. 27810882 6 40 theme expression 1295:1304 arg1 profiles 1306:1313 alternative expression profiles 1283:1313 alternative expression profiles 1283:1313 The results expand our view of a well-described adherence factor to show alternative expression profiles and adhesin specificities, which in turn may confer an advantage for certain isolates in alternative hosts and habitats. 27810882 6 41 theme factor 1268:1273 arg1 view 1233:1236 our view 1229:1236 our view of a well-described adherence factor to show alternative expression profiles and adhesin specificities, which in turn may confer an advantage for certain isolates in alternative hosts and habitats 1229:1433 The results expand our view of a well-described adherence factor to show alternative expression profiles and adhesin specificities, which in turn may confer an advantage for certain isolates in alternative hosts and habitats. 27810882 4 42 theme switch 892:897 arg1 fimS 900:903 the genetic switch (fimS) 880:904 the genetic switch (fimS) that controls phase variation 880:934 The heterogeneous proportions varied widely, and although growth temperature impacted the total proportion expressing T1F, there was no direct correlation between growth at 37°C and 20°C, indicative of differences in thermoregulation of the genetic switch (fimS) that controls phase variation. 27810882 0 43 dep Escherichia 53:63 arg1 coli 65:68 coli 65:68 coli 65:68 Alternate thermoregulation and functional binding of Escherichia coli type 1 fimbriae in environmental and animal isolates. 27810882 6 44 theme alternative 1283:1293 arg1 profiles 1306:1313 alternative expression profiles 1283:1313 alternative expression profiles 1283:1313 The results expand our view of a well-described adherence factor to show alternative expression profiles and adhesin specificities, which in turn may confer an advantage for certain isolates in alternative hosts and habitats. 27810882 5 45 from plants 1136:1141 arg1 -mannans 1095:1102 some recognised β-(1-4)-mannans 1072:1102 some recognised β-(1-4)-mannans 1072:1102 Specificities of the adhesin (FimH) also varied between the isolates: most bound to α-(1-3) mannan and yeast extracts as expected, but some recognised β-(1-4)-mannans and N-linked glycoproteins from plants, and T1F from two of the isolates mediated binding to plant roots. 27810882 5 45 from plants 1136:1141 arg1 glycoproteins 1117:1129 N-linked glycoproteins 1108:1129 N-linked glycoproteins 1108:1129 Specificities of the adhesin (FimH) also varied between the isolates: most bound to α-(1-3) mannan and yeast extracts as expected, but some recognised β-(1-4)-mannans and N-linked glycoproteins from plants, and T1F from two of the isolates mediated binding to plant roots. 27810882 4 46 theme phase 920:924 arg1 variation 926:934 phase variation 920:934 phase variation 920:934 The heterogeneous proportions varied widely, and although growth temperature impacted the total proportion expressing T1F, there was no direct correlation between growth at 37°C and 20°C, indicative of differences in thermoregulation of the genetic switch (fimS) that controls phase variation. 27810882 2 47 dep Koch 302:305 arg1 postulates 309:318 postulates 309:318 postulates as a virulence determinant 309:345 They satisfy molecular Koch's postulates as a virulence determinant and a host-adapted role has been reinforced by reports that T1F expression is repressed at submammalian temperatures. 27810882 0 48 theme Escherichia 53:63 arg1 fimbriae 77:84 Escherichia coli type 1 fimbriae 53:84 Escherichia coli type 1 fimbriae 53:84 Alternate thermoregulation and functional binding of Escherichia coli type 1 fimbriae in environmental and animal isolates. 27810882 4 49 theme differences 845:855 arg1 indicative 831:840 indicative 831:840 indicative 831:840 The heterogeneous proportions varied widely, and although growth temperature impacted the total proportion expressing T1F, there was no direct correlation between growth at 37°C and 20°C, indicative of differences in thermoregulation of the genetic switch (fimS) that controls phase variation. 27810882 3 50 theme variable 626:633 arg1 manner 635:640 a phase variable manner 618:640 a phase variable manner 618:640 Analysis of a group of 136 environmental and animal E. coli isolates that express T1F at 37°C showed that 28% are also capable of expression at 20°C, in a phase variable manner. 27810882 1 51 theme Type 124:127 arg1 T1F 141:143 T1F 141:143 T1F 141:143 Type 1 fimbriae (T1F) are well characterised cell surface organelles expressed by Escherichia coli and required for adherence to mannosylated host tissue. 27810882 1 51 theme Type 124:127 arg1 fimbriae 131:138 Type 1 fimbriae 124:138 Type 1 fimbriae (T1F) 124:144 Type 1 fimbriae (T1F) are well characterised cell surface organelles expressed by Escherichia coli and required for adherence to mannosylated host tissue. 27810882 1 51 theme Type 124:127 arg1 organelles 182:191 well characterised cell surface organelles 150:191 well characterised cell surface organelles expressed by Escherichia coli and required for adherence to mannosylated host tissue 150:276 Type 1 fimbriae (T1F) are well characterised cell surface organelles expressed by Escherichia coli and required for adherence to mannosylated host tissue. 27810882 6 52 theme adherence 1258:1266 arg1 factor 1268:1273 a well-described adherence factor 1241:1273 a well-described adherence factor 1241:1273 The results expand our view of a well-described adherence factor to show alternative expression profiles and adhesin specificities, which in turn may confer an advantage for certain isolates in alternative hosts and habitats. 27810882 5 53 gly glycoproteins 1117:1129 arg1 glycoproteins 1117:1129 N-linked glycoproteins 1108:1129 N-linked glycoproteins 1108:1129 Specificities of the adhesin (FimH) also varied between the isolates: most bound to α-(1-3) mannan and yeast extracts as expected, but some recognised β-(1-4)-mannans and N-linked glycoproteins from plants, and T1F from two of the isolates mediated binding to plant roots. 27810882 6 54 theme adhesin 1319:1325 arg1 specificities 1327:1339 adhesin specificities 1319:1339 adhesin specificities 1319:1339 The results expand our view of a well-described adherence factor to show alternative expression profiles and adhesin specificities, which in turn may confer an advantage for certain isolates in alternative hosts and habitats. 27810882 5 55 from T1F 1148:1150 arg1 -mannans 1095:1102 some recognised β-(1-4)-mannans 1072:1102 some recognised β-(1-4)-mannans 1072:1102 Specificities of the adhesin (FimH) also varied between the isolates: most bound to α-(1-3) mannan and yeast extracts as expected, but some recognised β-(1-4)-mannans and N-linked glycoproteins from plants, and T1F from two of the isolates mediated binding to plant roots. 27810882 5 55 from T1F 1148:1150 arg1 glycoproteins 1117:1129 N-linked glycoproteins 1108:1129 N-linked glycoproteins 1108:1129 Specificities of the adhesin (FimH) also varied between the isolates: most bound to α-(1-3) mannan and yeast extracts as expected, but some recognised β-(1-4)-mannans and N-linked glycoproteins from plants, and T1F from two of the isolates mediated binding to plant roots. 27810882 3 56 theme expression 595:604 arg1 capable 584:590 capable 584:590 capable 584:590 Analysis of a group of 136 environmental and animal E. coli isolates that express T1F at 37°C showed that 28% are also capable of expression at 20°C, in a phase variable manner. 27810882 3 57 theme E. 517:518 arg1 isolates 525:532 136 environmental and animal E. coli isolates 488:532 136 environmental and animal E. coli isolates that express T1F at 37°C 488:557 Analysis of a group of 136 environmental and animal E. coli isolates that express T1F at 37°C showed that 28% are also capable of expression at 20°C, in a phase variable manner. 27810882 5 58 theme isolates 1168:1175 arg1 two 1157:1159 two 1157:1159 two 1157:1159 Specificities of the adhesin (FimH) also varied between the isolates: most bound to α-(1-3) mannan and yeast extracts as expected, but some recognised β-(1-4)-mannans and N-linked glycoproteins from plants, and T1F from two of the isolates mediated binding to plant roots. 27810882 5 58 theme isolates 1168:1175 arg1 isolates 1168:1175 the isolates 1164:1175 the isolates 1164:1175 Specificities of the adhesin (FimH) also varied between the isolates: most bound to α-(1-3) mannan and yeast extracts as expected, but some recognised β-(1-4)-mannans and N-linked glycoproteins from plants, and T1F from two of the isolates mediated binding to plant roots. 27810882 4 59 from differences 845:855 arg1 thermoregulation 860:875 thermoregulation 860:875 thermoregulation of the genetic switch (fimS) that controls phase variation 860:934 The heterogeneous proportions varied widely, and although growth temperature impacted the total proportion expressing T1F, there was no direct correlation between growth at 37°C and 20°C, indicative of differences in thermoregulation of the genetic switch (fimS) that controls phase variation. 27810882 1 60 dep organelles 182:191 arg1 required 227:234 required 227:234 required for adherence to mannosylated host tissue 227:276 Type 1 fimbriae (T1F) are well characterised cell surface organelles expressed by Escherichia coli and required for adherence to mannosylated host tissue. 27810882 1 60 dep organelles 182:191 arg1 expressed 193:201 expressed 193:201 expressed by Escherichia coli 193:221 Type 1 fimbriae (T1F) are well characterised cell surface organelles expressed by Escherichia coli and required for adherence to mannosylated host tissue. 27810882 3 61 theme animal 510:515 arg1 isolates 525:532 136 environmental and animal E. coli isolates 488:532 136 environmental and animal E. coli isolates that express T1F at 37°C 488:557 Analysis of a group of 136 environmental and animal E. coli isolates that express T1F at 37°C showed that 28% are also capable of expression at 20°C, in a phase variable manner. 27810882 3 62 theme group 479:483 arg1 Analysis 465:472 Analysis 465:472 Analysis of a group of 136 environmental and animal E. coli isolates that express T1F at 37°C 465:557 Analysis of a group of 136 environmental and animal E. coli isolates that express T1F at 37°C showed that 28% are also capable of expression at 20°C, in a phase variable manner. 27810882 0 63 theme type 70:73 arg1 fimbriae 77:84 Escherichia coli type 1 fimbriae 53:84 Escherichia coli type 1 fimbriae 53:84 Alternate thermoregulation and functional binding of Escherichia coli type 1 fimbriae in environmental and animal isolates. 27810882 2 64 theme host-adapted 353:364 arg1 role 366:369 a host-adapted role 351:369 a host-adapted role 351:369 They satisfy molecular Koch's postulates as a virulence determinant and a host-adapted role has been reinforced by reports that T1F expression is repressed at submammalian temperatures. 27810882 3 65 from 20°C 609:612 arg1 expression 595:604 expression 595:604 expression at 20°C 595:612 Analysis of a group of 136 environmental and animal E. coli isolates that express T1F at 37°C showed that 28% are also capable of expression at 20°C, in a phase variable manner. 27749016 4 0 theme indolent 642:649 arg1 disease 651:657 indolent disease 642:657 indolent disease 642:657 Thus, the development of novel approaches specific for prostate cancer that can differentiate aggressive from indolent disease remains an urgent medical need. 27749016 6 1 theme phase 982:986 arg1 extraction 988:997 solid phase extraction 976:997 solid phase extraction of N-linked glycosite-containing peptides and LC-MS/MS 976:1052 Glycoproteins from urine samples of prostate cancer patients with different Gleason scores were characterized via solid phase extraction of N-linked glycosite-containing peptides and LC-MS/MS. 27749016 5 2 from patients 763:770 arg1 specimens 732:740 urine specimens 726:740 urine specimens from prostate cancer patients 726:770 In the current study, we evaluated urine specimens from prostate cancer patients using LC-MS/MS, with the aim of identifying effective urinary prostate cancer biomarkers. 27749016 3 3 theme indolent 469:476 arg1 cancers 487:493 indolent prostate cancers 469:493 indolent prostate cancers 469:493 However, blood prostate-specific antigen levels are less effective in distinguishing aggressive from indolent prostate cancers and other benign prostatic diseases. 27749016 8 4 gly glycoproteins 1330:1342 arg1 glycoproteins 1330:1342 AG prostate cancer associated glycoproteins 1300:1342 AG prostate cancer associated glycoproteins 1300:1342 Glycoproteomic comparison on urine and tissues from aggressive and non-aggressive prostate cancers as well as sera from prostate cancer patients revealed that the majority of AG prostate cancer associated glycoproteins were more readily detected in patient's urine than serum samples. 27749016 8 5 theme prostate 1303:1310 arg1 cancer 1312:1317 AG prostate cancer 1300:1317 AG prostate cancer 1300:1317 Glycoproteomic comparison on urine and tissues from aggressive and non-aggressive prostate cancers as well as sera from prostate cancer patients revealed that the majority of AG prostate cancer associated glycoproteins were more readily detected in patient's urine than serum samples. 27749016 5 6 theme current 698:704 arg1 study 706:710 the current study 694:710 the current study 694:710 In the current study, we evaluated urine specimens from prostate cancer patients using LC-MS/MS, with the aim of identifying effective urinary prostate cancer biomarkers. 27749016 8 7 theme associated 1319:1328 arg1 glycoproteins 1330:1342 AG prostate cancer associated glycoproteins 1300:1342 AG prostate cancer associated glycoproteins 1300:1342 Glycoproteomic comparison on urine and tissues from aggressive and non-aggressive prostate cancers as well as sera from prostate cancer patients revealed that the majority of AG prostate cancer associated glycoproteins were more readily detected in patient's urine than serum samples. 27749016 1 8 theme available 209:217 arg1 tests 219:223 available tests 209:223 available tests 209:223 Clinical management of prostate cancer remains a significant challenge due to the lack of available tests for guiding treatment decisions. 27749016 8 9 from comparison 1140:1149 arg1 urine 1154:1158 urine 1154:1158 urine 1154:1158 Glycoproteomic comparison on urine and tissues from aggressive and non-aggressive prostate cancers as well as sera from prostate cancer patients revealed that the majority of AG prostate cancer associated glycoproteins were more readily detected in patient's urine than serum samples. 27749016 8 9 from comparison 1140:1149 arg1 tissues 1164:1170 tissues 1164:1170 tissues 1164:1170 Glycoproteomic comparison on urine and tissues from aggressive and non-aggressive prostate cancers as well as sera from prostate cancer patients revealed that the majority of AG prostate cancer associated glycoproteins were more readily detected in patient's urine than serum samples. 27749016 6 10 theme glycosite-containing 1011:1030 arg1 peptides 1032:1039 N-linked glycosite-containing peptides 1002:1039 N-linked glycosite-containing peptides 1002:1039 Glycoproteins from urine samples of prostate cancer patients with different Gleason scores were characterized via solid phase extraction of N-linked glycosite-containing peptides and LC-MS/MS. 27749016 9 11 with patients 1505:1512 arg1 cancer 1531:1536 AG prostate cancer 1519:1536 AG prostate cancer 1519:1536 Our data collectively indicate that urine provides a potential source for biomarker testing in patients with AG prostate cancer. 27749016 5 12 theme prostate 747:754 arg1 patients 763:770 prostate cancer patients 747:770 prostate cancer patients 747:770 In the current study, we evaluated urine specimens from prostate cancer patients using LC-MS/MS, with the aim of identifying effective urinary prostate cancer biomarkers. 27749016 2 13 theme prostate-specific 268:284 arg1 test 294:297 The blood prostate-specific antigen test 258:297 The blood prostate-specific antigen test 258:297 The blood prostate-specific antigen test has facilitated early detection and intervention of prostate cancer. 27749016 7 14 theme glycosite-containing 1078:1097 arg1 peptides 1099:1106 2923 unique glycosite-containing peptides 1066:1106 2923 unique glycosite-containing peptides 1066:1106 A total of 2923 unique glycosite-containing peptides were identified. 27749016 1 15 theme cancer 151:156 arg1 management 128:137 Clinical management 119:137 Clinical management of prostate cancer 119:156 Clinical management of prostate cancer remains a significant challenge due to the lack of available tests for guiding treatment decisions. 27749016 8 16 from cancers 1216:1222 arg1 urine 1154:1158 urine 1154:1158 urine 1154:1158 Glycoproteomic comparison on urine and tissues from aggressive and non-aggressive prostate cancers as well as sera from prostate cancer patients revealed that the majority of AG prostate cancer associated glycoproteins were more readily detected in patient's urine than serum samples. 27749016 8 16 from cancers 1216:1222 arg1 tissues 1164:1170 tissues 1164:1170 tissues 1164:1170 Glycoproteomic comparison on urine and tissues from aggressive and non-aggressive prostate cancers as well as sera from prostate cancer patients revealed that the majority of AG prostate cancer associated glycoproteins were more readily detected in patient's urine than serum samples. 27749016 7 17 theme 2923 1066:1069 arg1 peptides 1099:1106 2923 unique glycosite-containing peptides 1066:1106 2923 unique glycosite-containing peptides 1066:1106 A total of 2923 unique glycosite-containing peptides were identified. 27749016 5 18 theme urinary 826:832 arg1 biomarkers 850:859 effective urinary prostate cancer biomarkers 816:859 effective urinary prostate cancer biomarkers 816:859 In the current study, we evaluated urine specimens from prostate cancer patients using LC-MS/MS, with the aim of identifying effective urinary prostate cancer biomarkers. 27749016 8 19 from sera 1235:1238 arg1 urine 1154:1158 urine 1154:1158 urine 1154:1158 Glycoproteomic comparison on urine and tissues from aggressive and non-aggressive prostate cancers as well as sera from prostate cancer patients revealed that the majority of AG prostate cancer associated glycoproteins were more readily detected in patient's urine than serum samples. 27749016 8 19 from sera 1235:1238 arg1 tissues 1164:1170 tissues 1164:1170 tissues 1164:1170 Glycoproteomic comparison on urine and tissues from aggressive and non-aggressive prostate cancers as well as sera from prostate cancer patients revealed that the majority of AG prostate cancer associated glycoproteins were more readily detected in patient's urine than serum samples. 27749016 3 20 theme prostate-specific 383:399 arg1 antigen 401:407 blood prostate-specific antigen 377:407 blood prostate-specific antigen levels 377:414 However, blood prostate-specific antigen levels are less effective in distinguishing aggressive from indolent prostate cancers and other benign prostatic diseases. 27749016 4 21 theme novel 557:561 arg1 approaches 563:572 novel approaches 557:572 novel approaches specific for prostate cancer that can differentiate aggressive from indolent disease 557:657 Thus, the development of novel approaches specific for prostate cancer that can differentiate aggressive from indolent disease remains an urgent medical need. 27749016 0 22 theme mass 100:103 arg1 spectrometry 105:116 mass spectrometry 100:116 mass spectrometry 100:116 Detection of aggressive prostate cancer associated glycoproteins in urine using glycoproteomics and mass spectrometry. 27749016 9 23 from testing 1494:1500 arg1 patients 1505:1512 patients 1505:1512 patients with AG prostate cancer 1505:1536 Our data collectively indicate that urine provides a potential source for biomarker testing in patients with AG prostate cancer. 27749016 0 24 from glycoproteins 51:63 arg1 urine 68:72 urine 68:72 urine using glycoproteomics and mass spectrometry 68:116 Detection of aggressive prostate cancer associated glycoproteins in urine using glycoproteomics and mass spectrometry. 27749016 6 25 link N-linked 1002:1009 arg1 peptides 1032:1039 N-linked glycosite-containing peptides 1002:1039 N-linked glycosite-containing peptides 1002:1039 Glycoproteins from urine samples of prostate cancer patients with different Gleason scores were characterized via solid phase extraction of N-linked glycosite-containing peptides and LC-MS/MS. 27749016 8 26 theme aggressive 1177:1186 arg1 cancers 1216:1222 aggressive and non-aggressive prostate cancers 1177:1222 aggressive and non-aggressive prostate cancers as well as sera from prostate cancer patients 1177:1268 Glycoproteomic comparison on urine and tissues from aggressive and non-aggressive prostate cancers as well as sera from prostate cancer patients revealed that the majority of AG prostate cancer associated glycoproteins were more readily detected in patient's urine than serum samples. 27749016 6 27 theme Gleason 938:944 arg1 scores 946:951 different Gleason scores 928:951 different Gleason scores 928:951 Glycoproteins from urine samples of prostate cancer patients with different Gleason scores were characterized via solid phase extraction of N-linked glycosite-containing peptides and LC-MS/MS. 27749016 3 28 theme prostatic 512:520 arg1 diseases 522:529 other benign prostatic diseases 499:529 other benign prostatic diseases 499:529 However, blood prostate-specific antigen levels are less effective in distinguishing aggressive from indolent prostate cancers and other benign prostatic diseases. 27749016 0 29 theme aggressive 13:22 arg1 cancer 33:38 aggressive prostate cancer 13:38 aggressive prostate cancer 13:38 Detection of aggressive prostate cancer associated glycoproteins in urine using glycoproteomics and mass spectrometry. 27749016 8 30 theme non-aggressive 1192:1205 arg1 cancers 1216:1222 aggressive and non-aggressive prostate cancers 1177:1222 aggressive and non-aggressive prostate cancers as well as sera from prostate cancer patients 1177:1268 Glycoproteomic comparison on urine and tissues from aggressive and non-aggressive prostate cancers as well as sera from prostate cancer patients revealed that the majority of AG prostate cancer associated glycoproteins were more readily detected in patient's urine than serum samples. 27749016 1 31 theme Clinical 119:126 arg1 management 128:137 Clinical management 119:137 Clinical management of prostate cancer 119:156 Clinical management of prostate cancer remains a significant challenge due to the lack of available tests for guiding treatment decisions. 27749016 3 32 theme other 499:503 arg1 diseases 522:529 other benign prostatic diseases 499:529 other benign prostatic diseases 499:529 However, blood prostate-specific antigen levels are less effective in distinguishing aggressive from indolent prostate cancers and other benign prostatic diseases. 27749016 0 33 theme cancer 33:38 arg1 Detection 0:8 Detection 0:8 Detection of aggressive prostate cancer 0:38 Detection of aggressive prostate cancer associated glycoproteins in urine using glycoproteomics and mass spectrometry. 27749016 9 34 theme biomarker 1484:1492 arg1 testing 1494:1500 biomarker testing 1484:1500 biomarker testing in patients with AG prostate cancer 1484:1536 Our data collectively indicate that urine provides a potential source for biomarker testing in patients with AG prostate cancer. 27749016 5 35 theme cancer 843:848 arg1 biomarkers 850:859 effective urinary prostate cancer biomarkers 816:859 effective urinary prostate cancer biomarkers 816:859 In the current study, we evaluated urine specimens from prostate cancer patients using LC-MS/MS, with the aim of identifying effective urinary prostate cancer biomarkers. 27749016 6 36 theme different 928:936 arg1 scores 946:951 different Gleason scores 928:951 different Gleason scores 928:951 Glycoproteins from urine samples of prostate cancer patients with different Gleason scores were characterized via solid phase extraction of N-linked glycosite-containing peptides and LC-MS/MS. 27749016 4 37 theme specific 574:581 arg1 approaches 563:572 novel approaches 557:572 novel approaches specific for prostate cancer that can differentiate aggressive from indolent disease 557:657 Thus, the development of novel approaches specific for prostate cancer that can differentiate aggressive from indolent disease remains an urgent medical need. 27749016 8 38 dep associated 1319:1328 arg1 cancer 1312:1317 AG prostate cancer 1300:1317 AG prostate cancer 1300:1317 Glycoproteomic comparison on urine and tissues from aggressive and non-aggressive prostate cancers as well as sera from prostate cancer patients revealed that the majority of AG prostate cancer associated glycoproteins were more readily detected in patient's urine than serum samples. 27749016 6 39 theme patients 914:921 arg1 samples 887:893 urine samples 881:893 urine samples of prostate cancer patients with different Gleason scores 881:951 Glycoproteins from urine samples of prostate cancer patients with different Gleason scores were characterized via solid phase extraction of N-linked glycosite-containing peptides and LC-MS/MS. 27749016 4 40 theme prostate 587:594 arg1 cancer 596:601 prostate cancer 587:601 prostate cancer 587:601 Thus, the development of novel approaches specific for prostate cancer that can differentiate aggressive from indolent disease remains an urgent medical need. 27749016 2 41 theme cancer 360:365 arg1 intervention 335:346 intervention 335:346 intervention 335:346 The blood prostate-specific antigen test has facilitated early detection and intervention of prostate cancer. 27749016 2 41 theme cancer 360:365 arg1 detection 321:329 detection 321:329 detection 321:329 The blood prostate-specific antigen test has facilitated early detection and intervention of prostate cancer. 27749016 6 42 theme prostate 898:905 arg1 patients 914:921 prostate cancer patients 898:921 prostate cancer patients with different Gleason scores 898:951 Glycoproteins from urine samples of prostate cancer patients with different Gleason scores were characterized via solid phase extraction of N-linked glycosite-containing peptides and LC-MS/MS. 27749016 9 43 theme prostate 1522:1529 arg1 cancer 1531:1536 AG prostate cancer 1519:1536 AG prostate cancer 1519:1536 Our data collectively indicate that urine provides a potential source for biomarker testing in patients with AG prostate cancer. 27749016 8 44 theme prostate 1245:1252 arg1 patients 1261:1268 prostate cancer patients 1245:1268 prostate cancer patients 1245:1268 Glycoproteomic comparison on urine and tissues from aggressive and non-aggressive prostate cancers as well as sera from prostate cancer patients revealed that the majority of AG prostate cancer associated glycoproteins were more readily detected in patient's urine than serum samples. 27749016 6 45 theme N-linked 1002:1009 arg1 peptides 1032:1039 N-linked glycosite-containing peptides 1002:1039 N-linked glycosite-containing peptides 1002:1039 Glycoproteins from urine samples of prostate cancer patients with different Gleason scores were characterized via solid phase extraction of N-linked glycosite-containing peptides and LC-MS/MS. 27749016 4 46 theme medical 677:683 arg1 need 685:688 an urgent medical need 667:688 an urgent medical need 667:688 Thus, the development of novel approaches specific for prostate cancer that can differentiate aggressive from indolent disease remains an urgent medical need. 27749016 6 47 theme urine 881:885 arg1 samples 887:893 urine samples 881:893 urine samples of prostate cancer patients with different Gleason scores 881:951 Glycoproteins from urine samples of prostate cancer patients with different Gleason scores were characterized via solid phase extraction of N-linked glycosite-containing peptides and LC-MS/MS. 27749016 2 48 theme early 315:319 arg1 detection 321:329 detection 321:329 detection 321:329 The blood prostate-specific antigen test has facilitated early detection and intervention of prostate cancer. 27749016 6 49 theme solid 976:980 arg1 extraction 988:997 solid phase extraction 976:997 solid phase extraction of N-linked glycosite-containing peptides and LC-MS/MS 976:1052 Glycoproteins from urine samples of prostate cancer patients with different Gleason scores were characterized via solid phase extraction of N-linked glycosite-containing peptides and LC-MS/MS. 27749016 1 50 theme due 190:192 arg1 challenge 180:188 a significant challenge 166:188 a significant challenge due to the lack of available tests for guiding treatment decisions 166:255 Clinical management of prostate cancer remains a significant challenge due to the lack of available tests for guiding treatment decisions. 27749016 8 51 theme AG 1300:1301 arg1 cancer 1312:1317 AG prostate cancer 1300:1317 AG prostate cancer 1300:1317 Glycoproteomic comparison on urine and tissues from aggressive and non-aggressive prostate cancers as well as sera from prostate cancer patients revealed that the majority of AG prostate cancer associated glycoproteins were more readily detected in patient's urine than serum samples. 27749016 8 52 theme Glycoproteomic 1125:1138 arg1 comparison 1140:1149 Glycoproteomic comparison 1125:1149 Glycoproteomic comparison on urine and tissues from aggressive and non-aggressive prostate cancers as well as sera from prostate cancer patients 1125:1268 Glycoproteomic comparison on urine and tissues from aggressive and non-aggressive prostate cancers as well as sera from prostate cancer patients revealed that the majority of AG prostate cancer associated glycoproteins were more readily detected in patient's urine than serum samples. 27749016 5 53 theme cancer 756:761 arg1 patients 763:770 prostate cancer patients 747:770 prostate cancer patients 747:770 In the current study, we evaluated urine specimens from prostate cancer patients using LC-MS/MS, with the aim of identifying effective urinary prostate cancer biomarkers. 27749016 1 54 theme tests 219:223 arg1 lack 201:204 the lack 197:204 the lack of available tests for guiding treatment decisions 197:255 Clinical management of prostate cancer remains a significant challenge due to the lack of available tests for guiding treatment decisions. 27749016 8 55 theme glycoproteins 1330:1342 arg1 majority 1288:1295 the majority 1284:1295 the majority of AG prostate cancer associated glycoproteins 1284:1342 Glycoproteomic comparison on urine and tissues from aggressive and non-aggressive prostate cancers as well as sera from prostate cancer patients revealed that the majority of AG prostate cancer associated glycoproteins were more readily detected in patient's urine than serum samples. 27749016 6 56 theme LC-MS/MS 1045:1052 arg1 extraction 988:997 solid phase extraction 976:997 solid phase extraction of N-linked glycosite-containing peptides and LC-MS/MS 976:1052 Glycoproteins from urine samples of prostate cancer patients with different Gleason scores were characterized via solid phase extraction of N-linked glycosite-containing peptides and LC-MS/MS. 27749016 8 57 theme serum 1395:1399 arg1 samples 1401:1407 serum samples 1395:1407 serum samples 1395:1407 Glycoproteomic comparison on urine and tissues from aggressive and non-aggressive prostate cancers as well as sera from prostate cancer patients revealed that the majority of AG prostate cancer associated glycoproteins were more readily detected in patient's urine than serum samples. 27749016 5 58 theme urine 726:730 arg1 specimens 732:740 urine specimens 726:740 urine specimens from prostate cancer patients 726:770 In the current study, we evaluated urine specimens from prostate cancer patients using LC-MS/MS, with the aim of identifying effective urinary prostate cancer biomarkers. 27749016 6 59 theme peptides 1032:1039 arg1 extraction 988:997 solid phase extraction 976:997 solid phase extraction of N-linked glycosite-containing peptides and LC-MS/MS 976:1052 Glycoproteins from urine samples of prostate cancer patients with different Gleason scores were characterized via solid phase extraction of N-linked glycosite-containing peptides and LC-MS/MS. 27749016 2 60 theme antigen 286:292 arg1 test 294:297 The blood prostate-specific antigen test 258:297 The blood prostate-specific antigen test 258:297 The blood prostate-specific antigen test has facilitated early detection and intervention of prostate cancer. 27749016 1 61 theme prostate 142:149 arg1 cancer 151:156 prostate cancer 142:156 prostate cancer 142:156 Clinical management of prostate cancer remains a significant challenge due to the lack of available tests for guiding treatment decisions. 27749016 2 62 theme blood 262:266 arg1 test 294:297 The blood prostate-specific antigen test 258:297 The blood prostate-specific antigen test 258:297 The blood prostate-specific antigen test has facilitated early detection and intervention of prostate cancer. 27749016 7 63 theme peptides 1099:1106 arg1 total 1057:1061 A total 1055:1061 A total of 2923 unique glycosite-containing peptides 1055:1106 A total of 2923 unique glycosite-containing peptides were identified. 27749016 5 64 theme effective 816:824 arg1 biomarkers 850:859 effective urinary prostate cancer biomarkers 816:859 effective urinary prostate cancer biomarkers 816:859 In the current study, we evaluated urine specimens from prostate cancer patients using LC-MS/MS, with the aim of identifying effective urinary prostate cancer biomarkers. 27749016 8 65 located detected 1362:1369 arg2 majority 1288:1295 the majority 1284:1295 the majority of AG prostate cancer associated glycoproteins 1284:1342 Glycoproteomic comparison on urine and tissues from aggressive and non-aggressive prostate cancers as well as sera from prostate cancer patients revealed that the majority of AG prostate cancer associated glycoproteins were more readily detected in patient's urine than serum samples. 27749016 8 65 located detected 1362:1369 arg1 urine 1384:1388 patient's urine 1374:1388 patient's urine than serum samples 1374:1407 Glycoproteomic comparison on urine and tissues from aggressive and non-aggressive prostate cancers as well as sera from prostate cancer patients revealed that the majority of AG prostate cancer associated glycoproteins were more readily detected in patient's urine than serum samples. 27749016 7 66 theme unique 1071:1076 arg1 peptides 1099:1106 2923 unique glycosite-containing peptides 1066:1106 2923 unique glycosite-containing peptides 1066:1106 A total of 2923 unique glycosite-containing peptides were identified. 27749016 1 67 theme significant 168:178 arg1 challenge 180:188 a significant challenge 166:188 a significant challenge due to the lack of available tests for guiding treatment decisions 166:255 Clinical management of prostate cancer remains a significant challenge due to the lack of available tests for guiding treatment decisions. 27749016 4 68 theme approaches 563:572 arg1 development 542:552 the development 538:552 the development of novel approaches specific for prostate cancer that can differentiate aggressive from indolent disease 538:657 Thus, the development of novel approaches specific for prostate cancer that can differentiate aggressive from indolent disease remains an urgent medical need. 27749016 3 69 theme antigen 401:407 arg1 levels 409:414 blood prostate-specific antigen levels 377:414 blood prostate-specific antigen levels 377:414 However, blood prostate-specific antigen levels are less effective in distinguishing aggressive from indolent prostate cancers and other benign prostatic diseases. 27749016 3 70 theme blood 377:381 arg1 antigen 401:407 blood prostate-specific antigen 377:407 blood prostate-specific antigen levels 377:414 However, blood prostate-specific antigen levels are less effective in distinguishing aggressive from indolent prostate cancers and other benign prostatic diseases. 27749016 1 71 theme treatment 237:245 arg1 decisions 247:255 treatment decisions 237:255 treatment decisions 237:255 Clinical management of prostate cancer remains a significant challenge due to the lack of available tests for guiding treatment decisions. 27749016 6 72 from samples 887:893 arg1 Glycoproteins 862:874 Glycoproteins 862:874 Glycoproteins from urine samples of prostate cancer patients with different Gleason scores 862:951 Glycoproteins from urine samples of prostate cancer patients with different Gleason scores were characterized via solid phase extraction of N-linked glycosite-containing peptides and LC-MS/MS. 27749016 3 73 theme prostate 478:485 arg1 cancers 487:493 indolent prostate cancers 469:493 indolent prostate cancers 469:493 However, blood prostate-specific antigen levels are less effective in distinguishing aggressive from indolent prostate cancers and other benign prostatic diseases. 27749016 0 74 theme prostate 24:31 arg1 cancer 33:38 aggressive prostate cancer 13:38 aggressive prostate cancer 13:38 Detection of aggressive prostate cancer associated glycoproteins in urine using glycoproteomics and mass spectrometry. 27749016 9 75 theme potential 1463:1471 arg1 source 1473:1478 a potential source 1461:1478 a potential source for biomarker testing in patients with AG prostate cancer 1461:1536 Our data collectively indicate that urine provides a potential source for biomarker testing in patients with AG prostate cancer. 27749016 8 76 theme prostate 1207:1214 arg1 cancers 1216:1222 aggressive and non-aggressive prostate cancers 1177:1222 aggressive and non-aggressive prostate cancers as well as sera from prostate cancer patients 1177:1268 Glycoproteomic comparison on urine and tissues from aggressive and non-aggressive prostate cancers as well as sera from prostate cancer patients revealed that the majority of AG prostate cancer associated glycoproteins were more readily detected in patient's urine than serum samples. 27749016 5 77 theme prostate 834:841 arg1 biomarkers 850:859 effective urinary prostate cancer biomarkers 816:859 effective urinary prostate cancer biomarkers 816:859 In the current study, we evaluated urine specimens from prostate cancer patients using LC-MS/MS, with the aim of identifying effective urinary prostate cancer biomarkers. 27749016 8 78 from patients 1261:1268 arg1 cancers 1216:1222 aggressive and non-aggressive prostate cancers 1177:1222 aggressive and non-aggressive prostate cancers as well as sera from prostate cancer patients 1177:1268 Glycoproteomic comparison on urine and tissues from aggressive and non-aggressive prostate cancers as well as sera from prostate cancer patients revealed that the majority of AG prostate cancer associated glycoproteins were more readily detected in patient's urine than serum samples. 27749016 8 78 from patients 1261:1268 arg1 sera 1235:1238 sera 1235:1238 aggressive and non-aggressive prostate cancers as well as sera from prostate cancer patients 1177:1268 Glycoproteomic comparison on urine and tissues from aggressive and non-aggressive prostate cancers as well as sera from prostate cancer patients revealed that the majority of AG prostate cancer associated glycoproteins were more readily detected in patient's urine than serum samples. 27749016 6 79 with patients 914:921 arg1 scores 946:951 different Gleason scores 928:951 different Gleason scores 928:951 Glycoproteins from urine samples of prostate cancer patients with different Gleason scores were characterized via solid phase extraction of N-linked glycosite-containing peptides and LC-MS/MS. 27749016 3 80 theme benign 505:510 arg1 diseases 522:529 other benign prostatic diseases 499:529 other benign prostatic diseases 499:529 However, blood prostate-specific antigen levels are less effective in distinguishing aggressive from indolent prostate cancers and other benign prostatic diseases. 27749016 6 81 theme cancer 907:912 arg1 patients 914:921 prostate cancer patients 898:921 prostate cancer patients with different Gleason scores 898:951 Glycoproteins from urine samples of prostate cancer patients with different Gleason scores were characterized via solid phase extraction of N-linked glycosite-containing peptides and LC-MS/MS. 27749016 4 82 theme urgent 670:675 arg1 need 685:688 an urgent medical need 667:688 an urgent medical need 667:688 Thus, the development of novel approaches specific for prostate cancer that can differentiate aggressive from indolent disease remains an urgent medical need. 27749016 2 83 theme prostate 351:358 arg1 cancer 360:365 prostate cancer 351:365 prostate cancer 351:365 The blood prostate-specific antigen test has facilitated early detection and intervention of prostate cancer. 27749016 9 84 theme AG 1519:1520 arg1 cancer 1531:1536 AG prostate cancer 1519:1536 AG prostate cancer 1519:1536 Our data collectively indicate that urine provides a potential source for biomarker testing in patients with AG prostate cancer. 27749016 8 85 theme cancer 1254:1259 arg1 patients 1261:1268 prostate cancer patients 1245:1268 prostate cancer patients 1245:1268 Glycoproteomic comparison on urine and tissues from aggressive and non-aggressive prostate cancers as well as sera from prostate cancer patients revealed that the majority of AG prostate cancer associated glycoproteins were more readily detected in patient's urine than serum samples. 27749016 0 86 gly glycoproteins 51:63 arg1 glycoproteins 51:63 glycoproteins 51:63 glycoproteins in urine using glycoproteomics and mass spectrometry 51:116 Detection of aggressive prostate cancer associated glycoproteins in urine using glycoproteomics and mass spectrometry. 27028816 6 0 theme primary 817:823 arg1 analysis 835:842 the primary structure analysis 813:842 the primary structure analysis 813:842 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 1 theme casein 969:974 arg1 segments 1035:1042 five putative hydrophobic segments 1009:1042 five putative hydrophobic segments 1009:1042 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 1 theme casein 969:974 arg1 sites 1002:1006 casein kinase II phosphorylation sites 969:1006 casein kinase II phosphorylation sites 969:1006 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 3 2 theme laevis 451:456 arg1 cDNA 458:461 a Xenopus laevis cDNA 441:461 a Xenopus laevis cDNA predicted to encode the xCLCA3 gene 441:497 In an effort to identify novel CLCA genes in Xenopus laevis, we successfully cloned and characterized a Xenopus laevis cDNA predicted to encode the xCLCA3 gene. 27028816 1 3 theme anion 185:189 arg1 accessories 152:162 Calcium (Ca^(2+))-activated chloride channel accessories 107:162 Calcium (Ca^(2+))-activated chloride channel accessories (CLCAs) 107:170 Calcium (Ca^(2+))-activated chloride channel accessories (CLCAs) are putative anion channel-related proteins with diverse physiological functions. 27028816 1 3 theme anion 185:189 arg1 proteins 207:214 putative anion channel-related proteins 176:214 putative anion channel-related proteins with diverse physiological functions 176:251 Calcium (Ca^(2+))-activated chloride channel accessories (CLCAs) are putative anion channel-related proteins with diverse physiological functions. 27028816 6 4 theme metalloprotease 1059:1073 arg1 motif 1075:1079 the HExxH metalloprotease motif 1049:1079 the HExxH metalloprotease motif 1049:1079 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 3 5 theme xCLCA3 487:492 arg1 gene 494:497 the xCLCA3 gene 483:497 the xCLCA3 gene 483:497 In an effort to identify novel CLCA genes in Xenopus laevis, we successfully cloned and characterized a Xenopus laevis cDNA predicted to encode the xCLCA3 gene. 27028816 2 6 theme CLCA 264:267 arg1 diversity 269:277 CLCA diversity 264:277 CLCA diversity 264:277 Exploring CLCA diversity is important for prediction of gene structure and function. 27028816 6 7 theme signal 873:878 arg1 sequence 880:887 a predicted signal sequence 861:887 a predicted signal sequence 861:887 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 9 8 theme candidate 1523:1531 arg1 member 1545:1550 a candidate CLCA family member 1521:1550 a candidate CLCA family member 1521:1550 These results suggest that xCLCA3 may be a candidate CLCA family member as well as a metalloprotease, rather than just an ion channel accessory protein. 27028816 9 8 theme candidate 1523:1531 arg1 xCLCA3 1507:1512 xCLCA3 1507:1512 xCLCA3 1507:1512 These results suggest that xCLCA3 may be a candidate CLCA family member as well as a metalloprotease, rather than just an ion channel accessory protein. 27028816 6 9 theme hydrophobic 1023:1033 arg1 segments 1035:1042 five putative hydrophobic segments 1009:1042 five putative hydrophobic segments 1009:1042 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 9 theme hydrophobic 1023:1033 arg1 sites 1002:1006 casein kinase II phosphorylation sites 969:1006 casein kinase II phosphorylation sites 969:1006 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 1 10 theme chloride 135:142 arg1 channel 144:150 Calcium (Ca^(2+))-activated chloride channel 107:150 Calcium (Ca^(2+))-activated chloride channel accessories (CLCAs) 107:170 Calcium (Ca^(2+))-activated chloride channel accessories (CLCAs) are putative anion channel-related proteins with diverse physiological functions. 27028816 9 11 theme family 1538:1543 arg1 member 1545:1550 a candidate CLCA family member 1521:1550 a candidate CLCA family member 1521:1550 These results suggest that xCLCA3 may be a candidate CLCA family member as well as a metalloprotease, rather than just an ion channel accessory protein. 27028816 9 11 theme family 1538:1543 arg1 xCLCA3 1507:1512 xCLCA3 1507:1512 xCLCA3 1507:1512 These results suggest that xCLCA3 may be a candidate CLCA family member as well as a metalloprotease, rather than just an ion channel accessory protein. 27028816 4 12 theme ends 586:589 arg1 analysis 548:555 computational analysis 534:555 computational analysis 534:555 Cloning of xCLCA3 was achieved by computational analysis, rapid amplification of cDNA ends (RACE), and a tissue distribution analysis by semi-quantitative reverse transcription (RT) PCR or real-time PCR. 27028816 4 12 theme ends 586:589 arg1 amplification 564:576 rapid amplification 558:576 rapid amplification of cDNA ends (RACE) 558:596 Cloning of xCLCA3 was achieved by computational analysis, rapid amplification of cDNA ends (RACE), and a tissue distribution analysis by semi-quantitative reverse transcription (RT) PCR or real-time PCR. 27028816 4 12 theme ends 586:589 arg1 analysis 625:632 a tissue distribution analysis 603:632 a tissue distribution analysis 603:632 Cloning of xCLCA3 was achieved by computational analysis, rapid amplification of cDNA ends (RACE), and a tissue distribution analysis by semi-quantitative reverse transcription (RT) PCR or real-time PCR. 27028816 5 13 theme xCLCA3 726:731 arg1 sequence 738:745 a 2958 bp xCLCA3 cDNA sequence 716:745 a 2958 bp xCLCA3 cDNA sequence with an open reading frame encoding 943 amino acids 716:797 We obtained a 2958 bp xCLCA3 cDNA sequence with an open reading frame encoding 943 amino acids. 27028816 5 14 theme open 755:758 arg1 frame 768:772 an open reading frame 752:772 an open reading frame encoding 943 amino acids 752:797 We obtained a 2958 bp xCLCA3 cDNA sequence with an open reading frame encoding 943 amino acids. 27028816 8 15 theme tissues 1340:1346 arg1 number 1330:1335 a number 1328:1335 a number of tissues, with strong expression in the brain, colon, small intestine, lung, kidney, and spleen, 1328:1434 Expression analysis showed that xCLCA3 is expressed in a number of tissues, with strong expression in the brain, colon, small intestine, lung, kidney, and spleen, and poor expression in the heart and liver. 27028816 8 15 theme tissues 1340:1346 arg1 expression 1445:1454 poor expression 1440:1454 poor expression in the heart and liver 1440:1477 Expression analysis showed that xCLCA3 is expressed in a number of tissues, with strong expression in the brain, colon, small intestine, lung, kidney, and spleen, and poor expression in the heart and liver. 27028816 7 16 theme C-terminal 1254:1263 arg1 region 1265:1270 the C-terminal region 1250:1270 the C-terminal region 1250:1270 Additionally, the transmembrane prediction server yielded a preserved N-terminal CLCA domain and a von Willebrand factor type A domain with one transmembrane domain in the C-terminal region. 27028816 4 17 theme reverse 655:661 arg1 PCR 682:684 semi-quantitative reverse transcription (RT) PCR 637:684 semi-quantitative reverse transcription (RT) PCR 637:684 Cloning of xCLCA3 was achieved by computational analysis, rapid amplification of cDNA ends (RACE), and a tissue distribution analysis by semi-quantitative reverse transcription (RT) PCR or real-time PCR. 27028816 6 18 theme N- 918:919 arg1 glycosylation 922:934 N-linked (N-) glycosylation 908:934 N-linked (N-) glycosylation 908:934 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 7 19 theme transmembrane 1226:1238 arg1 domain 1240:1245 one transmembrane domain 1222:1245 one transmembrane domain in the C-terminal region 1222:1270 Additionally, the transmembrane prediction server yielded a preserved N-terminal CLCA domain and a von Willebrand factor type A domain with one transmembrane domain in the C-terminal region. 27028816 8 20 dep brain 1379:1383 arg1 the 1375:1377 the 1375:1377 the 1375:1377 Expression analysis showed that xCLCA3 is expressed in a number of tissues, with strong expression in the brain, colon, small intestine, lung, kidney, and spleen, and poor expression in the heart and liver. 27028816 1 21 theme Calcium 107:113 arg1 channel 144:150 Calcium (Ca^(2+))-activated chloride channel 107:150 Calcium (Ca^(2+))-activated chloride channel accessories (CLCAs) 107:170 Calcium (Ca^(2+))-activated chloride channel accessories (CLCAs) are putative anion channel-related proteins with diverse physiological functions. 27028816 6 22 theme N-linked 908:915 arg1 glycosylation 922:934 N-linked (N-) glycosylation 908:934 N-linked (N-) glycosylation 908:934 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 4 23 theme distribution 612:623 arg1 analysis 625:632 a tissue distribution analysis 603:632 a tissue distribution analysis 603:632 Cloning of xCLCA3 was achieved by computational analysis, rapid amplification of cDNA ends (RACE), and a tissue distribution analysis by semi-quantitative reverse transcription (RT) PCR or real-time PCR. 27028816 7 24 theme transmembrane 1100:1112 arg1 server 1125:1130 the transmembrane prediction server 1096:1130 the transmembrane prediction server 1096:1130 Additionally, the transmembrane prediction server yielded a preserved N-terminal CLCA domain and a von Willebrand factor type A domain with one transmembrane domain in the C-terminal region. 27028816 0 25 from [Identification 0:14 arg1 laevis 98:103 Xenopus laevis 90:103 Xenopus laevis 90:103 [Identification of a Novel Calcium (Ca^(2+))-Activated Chloride Channel Accessory Gene in Xenopus laevis]. 27028816 0 26 theme Chloride 55:62 arg1 Channel 64:70 a Novel Calcium (Ca^(2+))-Activated Chloride Channel 19:70 a Novel Calcium (Ca^(2+))-Activated Chloride Channel Accessory Gene 19:85 [Identification of a Novel Calcium (Ca^(2+))-Activated Chloride Channel Accessory Gene in Xenopus laevis]. 27028816 6 27 link N-linked 908:915 arg1 glycosylation 922:934 N-linked (N-) glycosylation 908:934 N-linked (N-) glycosylation 908:934 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 9 28 theme ion 1602:1604 arg1 protein 1624:1630 just an ion channel accessory protein 1594:1630 just an ion channel accessory protein 1594:1630 These results suggest that xCLCA3 may be a candidate CLCA family member as well as a metalloprotease, rather than just an ion channel accessory protein. 27028816 7 29 theme type 1203:1206 arg1 domain 1210:1215 a von Willebrand factor type A domain 1179:1215 a von Willebrand factor type A domain 1179:1215 Additionally, the transmembrane prediction server yielded a preserved N-terminal CLCA domain and a von Willebrand factor type A domain with one transmembrane domain in the C-terminal region. 27028816 0 30 theme Accessory 72:80 arg1 Gene 82:85 a Novel Calcium (Ca^(2+))-Activated Chloride Channel Accessory Gene 19:85 a Novel Calcium (Ca^(2+))-Activated Chloride Channel Accessory Gene 19:85 [Identification of a Novel Calcium (Ca^(2+))-Activated Chloride Channel Accessory Gene in Xenopus laevis]. 27028816 6 31 theme PKC 960:962 arg1 sites 899:903 multiple sites 890:903 multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments 890:1042 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 31 theme PKC 960:962 arg1 sites 1002:1006 casein kinase II phosphorylation sites 969:1006 casein kinase II phosphorylation sites 969:1006 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 31 theme PKC 960:962 arg1 glycosylation 922:934 N-linked (N-) glycosylation 908:934 N-linked (N-) glycosylation 908:934 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 31 theme PKC 960:962 arg1 N-myristoylation 937:952 N-myristoylation 937:952 N-myristoylation 937:952 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 31 theme PKC 960:962 arg1 sequence 880:887 a predicted signal sequence 861:887 a predicted signal sequence 861:887 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 31 theme PKC 960:962 arg1 PKA 955:957 PKA 955:957 PKA 955:957 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 31 theme PKC 960:962 arg1 motif 1075:1079 the HExxH metalloprotease motif 1049:1079 the HExxH metalloprotease motif 1049:1079 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 31 theme PKC 960:962 arg1 PKC 960:962 PKC 960:962 PKC 960:962 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 9 32 theme accessory 1614:1622 arg1 protein 1624:1630 just an ion channel accessory protein 1594:1630 just an ion channel accessory protein 1594:1630 These results suggest that xCLCA3 may be a candidate CLCA family member as well as a metalloprotease, rather than just an ion channel accessory protein. 27028816 3 33 theme CLCA 370:373 arg1 genes 375:379 novel CLCA genes 364:379 novel CLCA genes in Xenopus laevis 364:397 In an effort to identify novel CLCA genes in Xenopus laevis, we successfully cloned and characterized a Xenopus laevis cDNA predicted to encode the xCLCA3 gene. 27028816 5 34 theme bp 723:724 arg1 sequence 738:745 a 2958 bp xCLCA3 cDNA sequence 716:745 a 2958 bp xCLCA3 cDNA sequence with an open reading frame encoding 943 amino acids 716:797 We obtained a 2958 bp xCLCA3 cDNA sequence with an open reading frame encoding 943 amino acids. 27028816 6 35 theme PKA 955:957 arg1 sites 899:903 multiple sites 890:903 multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments 890:1042 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 35 theme PKA 955:957 arg1 sites 1002:1006 casein kinase II phosphorylation sites 969:1006 casein kinase II phosphorylation sites 969:1006 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 35 theme PKA 955:957 arg1 glycosylation 922:934 N-linked (N-) glycosylation 908:934 N-linked (N-) glycosylation 908:934 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 35 theme PKA 955:957 arg1 N-myristoylation 937:952 N-myristoylation 937:952 N-myristoylation 937:952 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 35 theme PKA 955:957 arg1 sequence 880:887 a predicted signal sequence 861:887 a predicted signal sequence 861:887 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 35 theme PKA 955:957 arg1 PKA 955:957 PKA 955:957 PKA 955:957 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 35 theme PKA 955:957 arg1 motif 1075:1079 the HExxH metalloprotease motif 1049:1079 the HExxH metalloprotease motif 1049:1079 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 35 theme PKA 955:957 arg1 PKC 960:962 PKC 960:962 PKC 960:962 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 8 36 theme Expression 1273:1282 arg1 analysis 1284:1291 Expression analysis 1273:1291 Expression analysis 1273:1291 Expression analysis showed that xCLCA3 is expressed in a number of tissues, with strong expression in the brain, colon, small intestine, lung, kidney, and spleen, and poor expression in the heart and liver. 27028816 5 37 theme cDNA 733:736 arg1 sequence 738:745 a 2958 bp xCLCA3 cDNA sequence 716:745 a 2958 bp xCLCA3 cDNA sequence with an open reading frame encoding 943 amino acids 716:797 We obtained a 2958 bp xCLCA3 cDNA sequence with an open reading frame encoding 943 amino acids. 27028816 6 38 theme N-myristoylation 937:952 arg1 sites 899:903 multiple sites 890:903 multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments 890:1042 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 38 theme N-myristoylation 937:952 arg1 sites 1002:1006 casein kinase II phosphorylation sites 969:1006 casein kinase II phosphorylation sites 969:1006 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 38 theme N-myristoylation 937:952 arg1 glycosylation 922:934 N-linked (N-) glycosylation 908:934 N-linked (N-) glycosylation 908:934 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 38 theme N-myristoylation 937:952 arg1 N-myristoylation 937:952 N-myristoylation 937:952 N-myristoylation 937:952 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 38 theme N-myristoylation 937:952 arg1 sequence 880:887 a predicted signal sequence 861:887 a predicted signal sequence 861:887 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 38 theme N-myristoylation 937:952 arg1 PKA 955:957 PKA 955:957 PKA 955:957 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 38 theme N-myristoylation 937:952 arg1 motif 1075:1079 the HExxH metalloprotease motif 1049:1079 the HExxH metalloprotease motif 1049:1079 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 38 theme N-myristoylation 937:952 arg1 PKC 960:962 PKC 960:962 PKC 960:962 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 5 39 with sequence 738:745 arg1 frame 768:772 an open reading frame 752:772 an open reading frame encoding 943 amino acids 752:797 We obtained a 2958 bp xCLCA3 cDNA sequence with an open reading frame encoding 943 amino acids. 27028816 0 40 theme Calcium 27:33 arg1 Channel 64:70 a Novel Calcium (Ca^(2+))-Activated Chloride Channel 19:70 a Novel Calcium (Ca^(2+))-Activated Chloride Channel Accessory Gene 19:85 [Identification of a Novel Calcium (Ca^(2+))-Activated Chloride Channel Accessory Gene in Xenopus laevis]. 27028816 7 41 theme Willebrand 1185:1194 arg1 factor 1196:1201 a von Willebrand factor 1179:1201 a von Willebrand factor type A domain 1179:1215 Additionally, the transmembrane prediction server yielded a preserved N-terminal CLCA domain and a von Willebrand factor type A domain with one transmembrane domain in the C-terminal region. 27028816 0 42 theme Ca^ 36:38 arg1 Channel 64:70 a Novel Calcium (Ca^(2+))-Activated Chloride Channel 19:70 a Novel Calcium (Ca^(2+))-Activated Chloride Channel Accessory Gene 19:85 [Identification of a Novel Calcium (Ca^(2+))-Activated Chloride Channel Accessory Gene in Xenopus laevis]. 27028816 1 43 dep channel 144:150 arg1 2+ 120:121 2+ 120:121 2+ 120:121 Calcium (Ca^(2+))-activated chloride channel accessories (CLCAs) are putative anion channel-related proteins with diverse physiological functions. 27028816 1 43 dep channel 144:150 arg1 Ca^ 116:118 Ca^ 116:118 Ca^(2+) 116:122 Calcium (Ca^(2+))-activated chloride channel accessories (CLCAs) are putative anion channel-related proteins with diverse physiological functions. 27028816 6 44 theme phosphorylation 986:1000 arg1 segments 1035:1042 five putative hydrophobic segments 1009:1042 five putative hydrophobic segments 1009:1042 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 44 theme phosphorylation 986:1000 arg1 sites 1002:1006 casein kinase II phosphorylation sites 969:1006 casein kinase II phosphorylation sites 969:1006 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 4 45 theme computational 534:546 arg1 analysis 548:555 computational analysis 534:555 computational analysis 534:555 Cloning of xCLCA3 was achieved by computational analysis, rapid amplification of cDNA ends (RACE), and a tissue distribution analysis by semi-quantitative reverse transcription (RT) PCR or real-time PCR. 27028816 6 46 theme glycosylation 922:934 arg1 sites 899:903 multiple sites 890:903 multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments 890:1042 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 46 theme glycosylation 922:934 arg1 sites 1002:1006 casein kinase II phosphorylation sites 969:1006 casein kinase II phosphorylation sites 969:1006 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 46 theme glycosylation 922:934 arg1 glycosylation 922:934 N-linked (N-) glycosylation 908:934 N-linked (N-) glycosylation 908:934 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 46 theme glycosylation 922:934 arg1 N-myristoylation 937:952 N-myristoylation 937:952 N-myristoylation 937:952 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 46 theme glycosylation 922:934 arg1 sequence 880:887 a predicted signal sequence 861:887 a predicted signal sequence 861:887 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 46 theme glycosylation 922:934 arg1 PKA 955:957 PKA 955:957 PKA 955:957 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 46 theme glycosylation 922:934 arg1 motif 1075:1079 the HExxH metalloprotease motif 1049:1079 the HExxH metalloprotease motif 1049:1079 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 46 theme glycosylation 922:934 arg1 PKC 960:962 PKC 960:962 PKC 960:962 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 3 47 from genes 375:379 arg1 laevis 392:397 Xenopus laevis 384:397 Xenopus laevis 384:397 In an effort to identify novel CLCA genes in Xenopus laevis, we successfully cloned and characterized a Xenopus laevis cDNA predicted to encode the xCLCA3 gene. 27028816 6 48 theme structure 825:833 arg1 analysis 835:842 the primary structure analysis 813:842 the primary structure analysis 813:842 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 49 theme kinase 976:981 arg1 segments 1035:1042 five putative hydrophobic segments 1009:1042 five putative hydrophobic segments 1009:1042 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 49 theme kinase 976:981 arg1 sites 1002:1006 casein kinase II phosphorylation sites 969:1006 casein kinase II phosphorylation sites 969:1006 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 2 50 theme gene 310:313 arg1 structure 315:323 gene structure 310:323 gene structure 310:323 Exploring CLCA diversity is important for prediction of gene structure and function. 27028816 1 51 theme putative 176:183 arg1 accessories 152:162 Calcium (Ca^(2+))-activated chloride channel accessories 107:162 Calcium (Ca^(2+))-activated chloride channel accessories (CLCAs) 107:170 Calcium (Ca^(2+))-activated chloride channel accessories (CLCAs) are putative anion channel-related proteins with diverse physiological functions. 27028816 1 51 theme putative 176:183 arg1 proteins 207:214 putative anion channel-related proteins 176:214 putative anion channel-related proteins with diverse physiological functions 176:251 Calcium (Ca^(2+))-activated chloride channel accessories (CLCAs) are putative anion channel-related proteins with diverse physiological functions. 27028816 4 52 theme xCLCA3 511:516 arg1 Cloning 500:506 Cloning 500:506 Cloning of xCLCA3 500:516 Cloning of xCLCA3 was achieved by computational analysis, rapid amplification of cDNA ends (RACE), and a tissue distribution analysis by semi-quantitative reverse transcription (RT) PCR or real-time PCR. 27028816 1 53 theme channel-related 191:205 arg1 accessories 152:162 Calcium (Ca^(2+))-activated chloride channel accessories 107:162 Calcium (Ca^(2+))-activated chloride channel accessories (CLCAs) 107:170 Calcium (Ca^(2+))-activated chloride channel accessories (CLCAs) are putative anion channel-related proteins with diverse physiological functions. 27028816 1 53 theme channel-related 191:205 arg1 proteins 207:214 putative anion channel-related proteins 176:214 putative anion channel-related proteins with diverse physiological functions 176:251 Calcium (Ca^(2+))-activated chloride channel accessories (CLCAs) are putative anion channel-related proteins with diverse physiological functions. 27028816 5 54 theme reading 760:766 arg1 frame 768:772 an open reading frame 752:772 an open reading frame encoding 943 amino acids 752:797 We obtained a 2958 bp xCLCA3 cDNA sequence with an open reading frame encoding 943 amino acids. 27028816 8 55 from number 1330:1335 arg1 liver 1473:1477 liver 1473:1477 liver 1473:1477 Expression analysis showed that xCLCA3 is expressed in a number of tissues, with strong expression in the brain, colon, small intestine, lung, kidney, and spleen, and poor expression in the heart and liver. 27028816 8 55 from number 1330:1335 arg1 heart 1463:1467 heart 1463:1467 heart 1463:1467 Expression analysis showed that xCLCA3 is expressed in a number of tissues, with strong expression in the brain, colon, small intestine, lung, kidney, and spleen, and poor expression in the heart and liver. 27028816 0 56 theme Xenopus 90:96 arg1 laevis 98:103 Xenopus laevis 90:103 Xenopus laevis 90:103 [Identification of a Novel Calcium (Ca^(2+))-Activated Chloride Channel Accessory Gene in Xenopus laevis]. 27028816 1 57 theme -activated 124:133 arg1 channel 144:150 Calcium (Ca^(2+))-activated chloride channel 107:150 Calcium (Ca^(2+))-activated chloride channel accessories (CLCAs) 107:170 Calcium (Ca^(2+))-activated chloride channel accessories (CLCAs) are putative anion channel-related proteins with diverse physiological functions. 27028816 6 58 theme predicted 863:871 arg1 sequence 880:887 a predicted signal sequence 861:887 a predicted signal sequence 861:887 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 9 59 theme CLCA 1533:1536 arg1 member 1545:1550 a candidate CLCA family member 1521:1550 a candidate CLCA family member 1521:1550 These results suggest that xCLCA3 may be a candidate CLCA family member as well as a metalloprotease, rather than just an ion channel accessory protein. 27028816 9 59 theme CLCA 1533:1536 arg1 xCLCA3 1507:1512 xCLCA3 1507:1512 xCLCA3 1507:1512 These results suggest that xCLCA3 may be a candidate CLCA family member as well as a metalloprotease, rather than just an ion channel accessory protein. 27028816 6 60 theme putative 1014:1021 arg1 segments 1035:1042 five putative hydrophobic segments 1009:1042 five putative hydrophobic segments 1009:1042 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 60 theme putative 1014:1021 arg1 sites 1002:1006 casein kinase II phosphorylation sites 969:1006 casein kinase II phosphorylation sites 969:1006 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 3 61 theme Xenopus 443:449 arg1 cDNA 458:461 a Xenopus laevis cDNA 441:461 a Xenopus laevis cDNA predicted to encode the xCLCA3 gene 441:497 In an effort to identify novel CLCA genes in Xenopus laevis, we successfully cloned and characterized a Xenopus laevis cDNA predicted to encode the xCLCA3 gene. 27028816 8 62 from expression 1445:1454 arg1 liver 1473:1477 liver 1473:1477 liver 1473:1477 Expression analysis showed that xCLCA3 is expressed in a number of tissues, with strong expression in the brain, colon, small intestine, lung, kidney, and spleen, and poor expression in the heart and liver. 27028816 8 62 from expression 1445:1454 arg1 heart 1463:1467 heart 1463:1467 heart 1463:1467 Expression analysis showed that xCLCA3 is expressed in a number of tissues, with strong expression in the brain, colon, small intestine, lung, kidney, and spleen, and poor expression in the heart and liver. 27028816 1 63 theme channel 144:150 arg1 proteins 207:214 putative anion channel-related proteins 176:214 putative anion channel-related proteins with diverse physiological functions 176:251 Calcium (Ca^(2+))-activated chloride channel accessories (CLCAs) are putative anion channel-related proteins with diverse physiological functions. 27028816 1 63 theme channel 144:150 arg1 CLCAs 165:169 CLCAs 165:169 CLCAs 165:169 Calcium (Ca^(2+))-activated chloride channel accessories (CLCAs) are putative anion channel-related proteins with diverse physiological functions. 27028816 1 63 theme channel 144:150 arg1 accessories 152:162 Calcium (Ca^(2+))-activated chloride channel accessories 107:162 Calcium (Ca^(2+))-activated chloride channel accessories (CLCAs) 107:170 Calcium (Ca^(2+))-activated chloride channel accessories (CLCAs) are putative anion channel-related proteins with diverse physiological functions. 27028816 4 64 theme cDNA 581:584 arg1 RACE 592:595 RACE 592:595 RACE 592:595 Cloning of xCLCA3 was achieved by computational analysis, rapid amplification of cDNA ends (RACE), and a tissue distribution analysis by semi-quantitative reverse transcription (RT) PCR or real-time PCR. 27028816 4 64 theme cDNA 581:584 arg1 ends 586:589 cDNA ends 581:589 cDNA ends (RACE) 581:596 Cloning of xCLCA3 was achieved by computational analysis, rapid amplification of cDNA ends (RACE), and a tissue distribution analysis by semi-quantitative reverse transcription (RT) PCR or real-time PCR. 27028816 1 65 dep diverse 221:227 arg1 physiological 229:241 physiological 229:241 physiological 229:241 Calcium (Ca^(2+))-activated chloride channel accessories (CLCAs) are putative anion channel-related proteins with diverse physiological functions. 27028816 8 66 theme strong 1354:1359 arg1 expression 1361:1370 strong expression 1354:1370 strong expression in the brain, colon, small intestine, lung, kidney, and spleen 1354:1433 Expression analysis showed that xCLCA3 is expressed in a number of tissues, with strong expression in the brain, colon, small intestine, lung, kidney, and spleen, and poor expression in the heart and liver. 27028816 4 67 theme semi-quantitative 637:653 arg1 PCR 682:684 semi-quantitative reverse transcription (RT) PCR 637:684 semi-quantitative reverse transcription (RT) PCR 637:684 Cloning of xCLCA3 was achieved by computational analysis, rapid amplification of cDNA ends (RACE), and a tissue distribution analysis by semi-quantitative reverse transcription (RT) PCR or real-time PCR. 27028816 7 68 theme CLCA 1163:1166 arg1 domain 1168:1173 a preserved N-terminal CLCA domain 1140:1173 a preserved N-terminal CLCA domain 1140:1173 Additionally, the transmembrane prediction server yielded a preserved N-terminal CLCA domain and a von Willebrand factor type A domain with one transmembrane domain in the C-terminal region. 27028816 7 69 theme prediction 1114:1123 arg1 server 1125:1130 the transmembrane prediction server 1096:1130 the transmembrane prediction server 1096:1130 Additionally, the transmembrane prediction server yielded a preserved N-terminal CLCA domain and a von Willebrand factor type A domain with one transmembrane domain in the C-terminal region. 27028816 5 70 theme amino 787:791 arg1 acids 793:797 943 amino acids 783:797 943 amino acids 783:797 We obtained a 2958 bp xCLCA3 cDNA sequence with an open reading frame encoding 943 amino acids. 27028816 8 71 theme poor 1440:1443 arg1 expression 1445:1454 poor expression 1440:1454 poor expression in the heart and liver 1440:1477 Expression analysis showed that xCLCA3 is expressed in a number of tissues, with strong expression in the brain, colon, small intestine, lung, kidney, and spleen, and poor expression in the heart and liver. 27028816 6 72 gly glycosylation 922:934 arg2 PKA 955:957 PKA 955:957 PKA 955:957 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 72 gly glycosylation 922:934 arg2 sites 1002:1006 casein kinase II phosphorylation sites 969:1006 casein kinase II phosphorylation sites 969:1006 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 72 gly glycosylation 922:934 arg2 PKC 960:962 PKC 960:962 PKC 960:962 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 72 gly glycosylation 922:934 arg2 sites 899:903 multiple sites 890:903 multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments 890:1042 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 72 gly glycosylation 922:934 arg2 glycosylation 922:934 N-linked (N-) glycosylation 908:934 N-linked (N-) glycosylation 908:934 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 72 gly glycosylation 922:934 arg2 N-myristoylation 937:952 N-myristoylation 937:952 N-myristoylation 937:952 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 8 73 from expression 1361:1370 arg1 intestine 1399:1407 small intestine 1393:1407 small intestine 1393:1407 Expression analysis showed that xCLCA3 is expressed in a number of tissues, with strong expression in the brain, colon, small intestine, lung, kidney, and spleen, and poor expression in the heart and liver. 27028816 8 73 from expression 1361:1370 arg1 spleen 1428:1433 spleen 1428:1433 spleen 1428:1433 Expression analysis showed that xCLCA3 is expressed in a number of tissues, with strong expression in the brain, colon, small intestine, lung, kidney, and spleen, and poor expression in the heart and liver. 27028816 8 73 from expression 1361:1370 arg1 brain 1379:1383 brain 1379:1383 brain 1379:1383 Expression analysis showed that xCLCA3 is expressed in a number of tissues, with strong expression in the brain, colon, small intestine, lung, kidney, and spleen, and poor expression in the heart and liver. 27028816 8 73 from expression 1361:1370 arg1 lung 1410:1413 lung 1410:1413 lung 1410:1413 Expression analysis showed that xCLCA3 is expressed in a number of tissues, with strong expression in the brain, colon, small intestine, lung, kidney, and spleen, and poor expression in the heart and liver. 27028816 8 73 from expression 1361:1370 arg1 colon 1386:1390 colon 1386:1390 colon 1386:1390 Expression analysis showed that xCLCA3 is expressed in a number of tissues, with strong expression in the brain, colon, small intestine, lung, kidney, and spleen, and poor expression in the heart and liver. 27028816 8 73 from expression 1361:1370 arg1 kidney 1416:1421 kidney 1416:1421 kidney 1416:1421 Expression analysis showed that xCLCA3 is expressed in a number of tissues, with strong expression in the brain, colon, small intestine, lung, kidney, and spleen, and poor expression in the heart and liver. 27028816 0 74 theme -Activated 44:53 arg1 Channel 64:70 a Novel Calcium (Ca^(2+))-Activated Chloride Channel 19:70 a Novel Calcium (Ca^(2+))-Activated Chloride Channel Accessory Gene 19:85 [Identification of a Novel Calcium (Ca^(2+))-Activated Chloride Channel Accessory Gene in Xenopus laevis]. 27028816 4 75 theme tissue 605:610 arg1 analysis 625:632 a tissue distribution analysis 603:632 a tissue distribution analysis 603:632 Cloning of xCLCA3 was achieved by computational analysis, rapid amplification of cDNA ends (RACE), and a tissue distribution analysis by semi-quantitative reverse transcription (RT) PCR or real-time PCR. 27028816 0 76 theme Channel 64:70 arg1 Gene 82:85 a Novel Calcium (Ca^(2+))-Activated Chloride Channel Accessory Gene 19:85 a Novel Calcium (Ca^(2+))-Activated Chloride Channel Accessory Gene 19:85 [Identification of a Novel Calcium (Ca^(2+))-Activated Chloride Channel Accessory Gene in Xenopus laevis]. 27028816 8 77 dep heart 1463:1467 arg1 the 1459:1461 the 1459:1461 the 1459:1461 Expression analysis showed that xCLCA3 is expressed in a number of tissues, with strong expression in the brain, colon, small intestine, lung, kidney, and spleen, and poor expression in the heart and liver. 27028816 6 78 theme multiple 890:897 arg1 sites 899:903 multiple sites 890:903 multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments 890:1042 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 78 theme multiple 890:897 arg1 sites 1002:1006 casein kinase II phosphorylation sites 969:1006 casein kinase II phosphorylation sites 969:1006 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 78 theme multiple 890:897 arg1 glycosylation 922:934 N-linked (N-) glycosylation 908:934 N-linked (N-) glycosylation 908:934 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 78 theme multiple 890:897 arg1 N-myristoylation 937:952 N-myristoylation 937:952 N-myristoylation 937:952 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 78 theme multiple 890:897 arg1 PKA 955:957 PKA 955:957 PKA 955:957 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 78 theme multiple 890:897 arg1 PKC 960:962 PKC 960:962 PKC 960:962 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 8 79 theme small 1393:1397 arg1 intestine 1399:1407 small intestine 1393:1407 small intestine 1393:1407 Expression analysis showed that xCLCA3 is expressed in a number of tissues, with strong expression in the brain, colon, small intestine, lung, kidney, and spleen, and poor expression in the heart and liver. 27028816 0 80 theme Gene 82:85 arg1 [Identification 0:14 [Identification 0:14 [Identification of a Novel Calcium (Ca^(2+))-Activated Chloride Channel Accessory Gene in Xenopus laevis 0:103 [Identification of a Novel Calcium (Ca^(2+))-Activated Chloride Channel Accessory Gene in Xenopus laevis]. 27028816 7 81 from domain 1240:1245 arg1 region 1265:1270 the C-terminal region 1250:1270 the C-terminal region 1250:1270 Additionally, the transmembrane prediction server yielded a preserved N-terminal CLCA domain and a von Willebrand factor type A domain with one transmembrane domain in the C-terminal region. 27028816 9 82 theme channel 1606:1612 arg1 protein 1624:1630 just an ion channel accessory protein 1594:1630 just an ion channel accessory protein 1594:1630 These results suggest that xCLCA3 may be a candidate CLCA family member as well as a metalloprotease, rather than just an ion channel accessory protein. 27028816 4 83 theme real-time 689:697 arg1 PCR 699:701 real-time PCR 689:701 real-time PCR 689:701 Cloning of xCLCA3 was achieved by computational analysis, rapid amplification of cDNA ends (RACE), and a tissue distribution analysis by semi-quantitative reverse transcription (RT) PCR or real-time PCR. 27028816 3 84 theme Xenopus 384:390 arg1 laevis 392:397 Xenopus laevis 384:397 Xenopus laevis 384:397 In an effort to identify novel CLCA genes in Xenopus laevis, we successfully cloned and characterized a Xenopus laevis cDNA predicted to encode the xCLCA3 gene. 27028816 5 85 theme 2958 718:721 arg1 bp 723:724 bp 723:724 bp 723:724 We obtained a 2958 bp xCLCA3 cDNA sequence with an open reading frame encoding 943 amino acids. 27028816 7 86 theme A 1208:1208 arg1 domain 1210:1215 a von Willebrand factor type A domain 1179:1215 a von Willebrand factor type A domain 1179:1215 Additionally, the transmembrane prediction server yielded a preserved N-terminal CLCA domain and a von Willebrand factor type A domain with one transmembrane domain in the C-terminal region. 27028816 4 87 theme transcription 663:675 arg1 PCR 682:684 semi-quantitative reverse transcription (RT) PCR 637:684 semi-quantitative reverse transcription (RT) PCR 637:684 Cloning of xCLCA3 was achieved by computational analysis, rapid amplification of cDNA ends (RACE), and a tissue distribution analysis by semi-quantitative reverse transcription (RT) PCR or real-time PCR. 27028816 2 88 theme function 329:336 arg1 prediction 296:305 prediction 296:305 prediction of gene structure and function 296:336 Exploring CLCA diversity is important for prediction of gene structure and function. 27028816 0 89 theme Novel 21:25 arg1 Channel 64:70 a Novel Calcium (Ca^(2+))-Activated Chloride Channel 19:70 a Novel Calcium (Ca^(2+))-Activated Chloride Channel Accessory Gene 19:85 [Identification of a Novel Calcium (Ca^(2+))-Activated Chloride Channel Accessory Gene in Xenopus laevis]. 27028816 1 90 theme diverse 221:227 arg1 functions 243:251 diverse physiological functions 221:251 diverse physiological functions 221:251 Calcium (Ca^(2+))-activated chloride channel accessories (CLCAs) are putative anion channel-related proteins with diverse physiological functions. 27028816 7 91 theme factor 1196:1201 arg1 domain 1210:1215 a von Willebrand factor type A domain 1179:1215 a von Willebrand factor type A domain 1179:1215 Additionally, the transmembrane prediction server yielded a preserved N-terminal CLCA domain and a von Willebrand factor type A domain with one transmembrane domain in the C-terminal region. 27028816 4 92 theme RT 678:679 arg1 PCR 682:684 semi-quantitative reverse transcription (RT) PCR 637:684 semi-quantitative reverse transcription (RT) PCR 637:684 Cloning of xCLCA3 was achieved by computational analysis, rapid amplification of cDNA ends (RACE), and a tissue distribution analysis by semi-quantitative reverse transcription (RT) PCR or real-time PCR. 27028816 6 93 theme II 983:984 arg1 segments 1035:1042 five putative hydrophobic segments 1009:1042 five putative hydrophobic segments 1009:1042 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 93 theme II 983:984 arg1 sites 1002:1006 casein kinase II phosphorylation sites 969:1006 casein kinase II phosphorylation sites 969:1006 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 7 94 theme von 1181:1183 arg1 factor 1196:1201 a von Willebrand factor 1179:1201 a von Willebrand factor type A domain 1179:1215 Additionally, the transmembrane prediction server yielded a preserved N-terminal CLCA domain and a von Willebrand factor type A domain with one transmembrane domain in the C-terminal region. 27028816 3 95 theme novel 364:368 arg1 genes 375:379 novel CLCA genes 364:379 novel CLCA genes in Xenopus laevis 364:397 In an effort to identify novel CLCA genes in Xenopus laevis, we successfully cloned and characterized a Xenopus laevis cDNA predicted to encode the xCLCA3 gene. 27028816 1 96 with proteins 207:214 arg1 functions 243:251 diverse physiological functions 221:251 diverse physiological functions 221:251 Calcium (Ca^(2+))-activated chloride channel accessories (CLCAs) are putative anion channel-related proteins with diverse physiological functions. 27028816 8 97 with tissues 1340:1346 arg1 expression 1361:1370 strong expression 1354:1370 strong expression in the brain, colon, small intestine, lung, kidney, and spleen 1354:1433 Expression analysis showed that xCLCA3 is expressed in a number of tissues, with strong expression in the brain, colon, small intestine, lung, kidney, and spleen, and poor expression in the heart and liver. 27028816 6 98 theme sites 1002:1006 arg1 sites 899:903 multiple sites 890:903 multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments 890:1042 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 98 theme sites 1002:1006 arg1 sites 1002:1006 casein kinase II phosphorylation sites 969:1006 casein kinase II phosphorylation sites 969:1006 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 98 theme sites 1002:1006 arg1 glycosylation 922:934 N-linked (N-) glycosylation 908:934 N-linked (N-) glycosylation 908:934 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 98 theme sites 1002:1006 arg1 N-myristoylation 937:952 N-myristoylation 937:952 N-myristoylation 937:952 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 98 theme sites 1002:1006 arg1 sequence 880:887 a predicted signal sequence 861:887 a predicted signal sequence 861:887 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 98 theme sites 1002:1006 arg1 PKA 955:957 PKA 955:957 PKA 955:957 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 98 theme sites 1002:1006 arg1 motif 1075:1079 the HExxH metalloprotease motif 1049:1079 the HExxH metalloprotease motif 1049:1079 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 98 theme sites 1002:1006 arg1 PKC 960:962 PKC 960:962 PKC 960:962 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 7 99 theme N-terminal 1152:1161 arg1 domain 1168:1173 a preserved N-terminal CLCA domain 1140:1173 a preserved N-terminal CLCA domain 1140:1173 Additionally, the transmembrane prediction server yielded a preserved N-terminal CLCA domain and a von Willebrand factor type A domain with one transmembrane domain in the C-terminal region. 27028816 7 100 theme preserved 1142:1150 arg1 domain 1168:1173 a preserved N-terminal CLCA domain 1140:1173 a preserved N-terminal CLCA domain 1140:1173 Additionally, the transmembrane prediction server yielded a preserved N-terminal CLCA domain and a von Willebrand factor type A domain with one transmembrane domain in the C-terminal region. 27028816 4 101 theme rapid 558:562 arg1 amplification 564:576 rapid amplification 558:576 rapid amplification of cDNA ends (RACE) 558:596 Cloning of xCLCA3 was achieved by computational analysis, rapid amplification of cDNA ends (RACE), and a tissue distribution analysis by semi-quantitative reverse transcription (RT) PCR or real-time PCR. 27028816 6 102 contain contains 852:859 arg2 PKA 955:957 PKA 955:957 PKA 955:957 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 102 contain contains 852:859 arg2 motif 1075:1079 the HExxH metalloprotease motif 1049:1079 the HExxH metalloprotease motif 1049:1079 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 102 contain contains 852:859 arg2 sites 1002:1006 casein kinase II phosphorylation sites 969:1006 casein kinase II phosphorylation sites 969:1006 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 102 contain contains 852:859 arg2 PKC 960:962 PKC 960:962 PKC 960:962 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 102 contain contains 852:859 arg2 sequence 880:887 a predicted signal sequence 861:887 a predicted signal sequence 861:887 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 102 contain contains 852:859 arg2 sites 899:903 multiple sites 890:903 multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments 890:1042 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 102 contain contains 852:859 arg1 xCLCA3 845:850 xCLCA3 845:850 xCLCA3 845:850 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 102 contain contains 852:859 arg2 glycosylation 922:934 N-linked (N-) glycosylation 908:934 N-linked (N-) glycosylation 908:934 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 6 102 contain contains 852:859 arg2 N-myristoylation 937:952 N-myristoylation 937:952 N-myristoylation 937:952 According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. 27028816 2 103 theme structure 315:323 arg1 prediction 296:305 prediction 296:305 prediction of gene structure and function 296:336 Exploring CLCA diversity is important for prediction of gene structure and function. 26405106 1 0 link N-linked 91:98 arg1 glycans 100:106 N-linked glycans 91:106 N-linked glycans 91:106 N-linked glycans are on protein surfaces and have direct and water/ion-mediated interactions with surrounding amino acids. 26405106 5 1 theme glycoprotein 693:704 arg1 structures 714:723 The glycoprotein crystal structures 689:723 The glycoprotein crystal structures 689:723 The glycoprotein crystal structures are analyzed to compare the conformational freedom of the N-glycan on the protein surface with the simulation result. 26405106 1 2 theme water/ion-mediated 152:169 arg1 interactions 171:182 direct and water/ion-mediated interactions 141:182 direct and water/ion-mediated interactions with surrounding amino acids 141:211 N-linked glycans are on protein surfaces and have direct and water/ion-mediated interactions with surrounding amino acids. 26405106 5 3 theme protein 799:805 arg1 surface 807:813 the protein surface 795:813 the protein surface 795:813 The glycoprotein crystal structures are analyzed to compare the conformational freedom of the N-glycan on the protein surface with the simulation result. 26405106 5 4 theme simulation 824:833 arg1 result 835:840 the simulation result 820:840 the simulation result 820:840 The glycoprotein crystal structures are analyzed to compare the conformational freedom of the N-glycan on the protein surface with the simulation result. 26405106 0 5 from conformations 10:22 arg1 glycoproteins 76:88 glycoproteins 76:88 glycoproteins 76:88 Preferred conformations of N-glycan core pentasaccharide in solution and in glycoproteins. 26405106 0 5 from conformations 10:22 arg1 solution 60:67 solution 60:67 solution 60:67 Preferred conformations of N-glycan core pentasaccharide in solution and in glycoproteins. 26405106 1 6 with interactions 171:182 arg1 acids 207:211 surrounding amino acids 189:211 surrounding amino acids 189:211 N-linked glycans are on protein surfaces and have direct and water/ion-mediated interactions with surrounding amino acids. 26405106 7 7 theme side 1043:1046 arg1 chain 1048:1052 the protein side chain 1031:1052 the protein side chain 1031:1052 The interactions between the carbohydrate and the protein side chain appear to be responsible for the increased conformational diversity of the N-glycan on the protein surface. 26405106 4 8 theme pentasaccharide 612:626 arg1 variability 593:603 the comparable conformational variability 563:603 the comparable conformational variability of the pentasaccharide in solution 563:638 Both simulations yield the comparable conformational variability of the pentasaccharide in solution, indicating the convergence of both simulations. 26405106 5 9 theme N-glycan 783:790 arg1 freedom 768:774 the conformational freedom 749:774 the conformational freedom of the N-glycan on the protein surface 749:813 The glycoprotein crystal structures are analyzed to compare the conformational freedom of the N-glycan on the protein surface with the simulation result. 26405106 6 10 theme free 877:880 arg1 pentasaccharide 861:875 the pentasaccharide 857:875 the pentasaccharide free in solution 857:892 Surprisingly, the pentasaccharide free in solution shows more restricted conformational variability than the N-glycan on the protein surface. 26405106 6 11 from N-glycan 952:959 arg1 surface 976:982 the protein surface 964:982 the protein surface 964:982 Surprisingly, the pentasaccharide free in solution shows more restricted conformational variability than the N-glycan on the protein surface. 26405106 6 12 theme protein 968:974 arg1 surface 976:982 the protein surface 964:982 the protein surface 964:982 Surprisingly, the pentasaccharide free in solution shows more restricted conformational variability than the N-glycan on the protein surface. 26405106 3 13 theme MD 524:525 arg1 simulations 527:537 temperature replica-exchange MD simulations 495:537 standard molecular dynamics (MD) simulations as well as temperature replica-exchange MD simulations 439:537 In this work, we have examined the conformational freedom of the N-glycan core pentasaccharide moiety in solution using standard molecular dynamics (MD) simulations as well as temperature replica-exchange MD simulations. 26405106 5 14 from freedom 768:774 arg1 surface 807:813 the protein surface 795:813 the protein surface 795:813 The glycoprotein crystal structures are analyzed to compare the conformational freedom of the N-glycan on the protein surface with the simulation result. 26405106 8 15 theme causality 1257:1265 arg1 relationship 1267:1278 an unexpected causality relationship 1243:1278 an unexpected causality relationship between intramolecular hydrogen bonds and the conformational states in that the hydrogen bonds play a role in maintaining the conformational states rather than driving the change in glycosidic torsional states 1243:1488 Finally, the transfer entropy analysis of the simulation trajectory also reveals an unexpected causality relationship between intramolecular hydrogen bonds and the conformational states in that the hydrogen bonds play a role in maintaining the conformational states rather than driving the change in glycosidic torsional states. 26405106 3 16 theme temperature 495:505 arg1 simulations 527:537 temperature replica-exchange MD simulations 495:537 standard molecular dynamics (MD) simulations as well as temperature replica-exchange MD simulations 439:537 In this work, we have examined the conformational freedom of the N-glycan core pentasaccharide moiety in solution using standard molecular dynamics (MD) simulations as well as temperature replica-exchange MD simulations. 26405106 7 17 theme protein 1035:1041 arg1 chain 1048:1052 the protein side chain 1031:1052 the protein side chain 1031:1052 The interactions between the carbohydrate and the protein side chain appear to be responsible for the increased conformational diversity of the N-glycan on the protein surface. 26405106 0 18 gly glycoproteins 76:88 arg1 glycoproteins 76:88 glycoproteins 76:88 glycoproteins 76:88 Preferred conformations of N-glycan core pentasaccharide in solution and in glycoproteins. 26405106 3 19 theme standard 439:446 arg1 simulations 472:482 standard molecular dynamics (MD) simulations 439:482 standard molecular dynamics (MD) simulations as well as temperature replica-exchange MD simulations 439:537 In this work, we have examined the conformational freedom of the N-glycan core pentasaccharide moiety in solution using standard molecular dynamics (MD) simulations as well as temperature replica-exchange MD simulations. 26405106 3 20 theme dynamics 458:465 arg1 simulations 472:482 standard molecular dynamics (MD) simulations 439:482 standard molecular dynamics (MD) simulations as well as temperature replica-exchange MD simulations 439:537 In this work, we have examined the conformational freedom of the N-glycan core pentasaccharide moiety in solution using standard molecular dynamics (MD) simulations as well as temperature replica-exchange MD simulations. 26405106 3 21 theme conformational 354:367 arg1 freedom 369:375 the conformational freedom 350:375 the conformational freedom of the N-glycan core pentasaccharide moiety in solution 350:431 In this work, we have examined the conformational freedom of the N-glycan core pentasaccharide moiety in solution using standard molecular dynamics (MD) simulations as well as temperature replica-exchange MD simulations. 26405106 3 22 theme pentasaccharide 398:412 arg1 moiety 414:419 the N-glycan core pentasaccharide moiety 380:419 the N-glycan core pentasaccharide moiety 380:419 In this work, we have examined the conformational freedom of the N-glycan core pentasaccharide moiety in solution using standard molecular dynamics (MD) simulations as well as temperature replica-exchange MD simulations. 26405106 1 23 theme surrounding 189:199 arg1 acids 207:211 surrounding amino acids 189:211 surrounding amino acids 189:211 N-linked glycans are on protein surfaces and have direct and water/ion-mediated interactions with surrounding amino acids. 26405106 3 24 theme core 393:396 arg1 moiety 414:419 the N-glycan core pentasaccharide moiety 380:419 the N-glycan core pentasaccharide moiety 380:419 In this work, we have examined the conformational freedom of the N-glycan core pentasaccharide moiety in solution using standard molecular dynamics (MD) simulations as well as temperature replica-exchange MD simulations. 26405106 8 25 theme trajectory 1219:1228 arg1 analysis 1192:1199 the transfer entropy analysis 1171:1199 the transfer entropy analysis of the simulation trajectory 1171:1228 Finally, the transfer entropy analysis of the simulation trajectory also reveals an unexpected causality relationship between intramolecular hydrogen bonds and the conformational states in that the hydrogen bonds play a role in maintaining the conformational states rather than driving the change in glycosidic torsional states. 26405106 8 26 theme unexpected 1246:1255 arg1 relationship 1267:1278 an unexpected causality relationship 1243:1278 an unexpected causality relationship between intramolecular hydrogen bonds and the conformational states in that the hydrogen bonds play a role in maintaining the conformational states rather than driving the change in glycosidic torsional states 1243:1488 Finally, the transfer entropy analysis of the simulation trajectory also reveals an unexpected causality relationship between intramolecular hydrogen bonds and the conformational states in that the hydrogen bonds play a role in maintaining the conformational states rather than driving the change in glycosidic torsional states. 26405106 1 27 theme N-linked 91:98 arg1 glycans 100:106 N-linked glycans 91:106 N-linked glycans 91:106 N-linked glycans are on protein surfaces and have direct and water/ion-mediated interactions with surrounding amino acids. 26405106 7 28 theme N-glycan 1129:1136 arg1 diversity 1112:1120 the increased conformational diversity 1083:1120 the increased conformational diversity of the N-glycan on the protein surface 1083:1159 The interactions between the carbohydrate and the protein side chain appear to be responsible for the increased conformational diversity of the N-glycan on the protein surface. 26405106 1 29 theme amino 201:205 arg1 acids 207:211 surrounding amino acids 189:211 surrounding amino acids 189:211 N-linked glycans are on protein surfaces and have direct and water/ion-mediated interactions with surrounding amino acids. 26405106 0 30 theme Preferred 0:8 arg1 conformations 10:22 Preferred conformations 0:22 Preferred conformations of N-glycan core pentasaccharide in solution and in glycoproteins 0:88 Preferred conformations of N-glycan core pentasaccharide in solution and in glycoproteins. 26405106 8 31 theme transfer 1175:1182 arg1 analysis 1192:1199 the transfer entropy analysis 1171:1199 the transfer entropy analysis of the simulation trajectory 1171:1228 Finally, the transfer entropy analysis of the simulation trajectory also reveals an unexpected causality relationship between intramolecular hydrogen bonds and the conformational states in that the hydrogen bonds play a role in maintaining the conformational states rather than driving the change in glycosidic torsional states. 26405106 8 32 theme glycosidic 1462:1471 arg1 states 1483:1488 glycosidic torsional states 1462:1488 glycosidic torsional states 1462:1488 Finally, the transfer entropy analysis of the simulation trajectory also reveals an unexpected causality relationship between intramolecular hydrogen bonds and the conformational states in that the hydrogen bonds play a role in maintaining the conformational states rather than driving the change in glycosidic torsional states. 26405106 3 33 theme molecular 448:456 arg1 simulations 472:482 standard molecular dynamics (MD) simulations 439:482 standard molecular dynamics (MD) simulations as well as temperature replica-exchange MD simulations 439:537 In this work, we have examined the conformational freedom of the N-glycan core pentasaccharide moiety in solution using standard molecular dynamics (MD) simulations as well as temperature replica-exchange MD simulations. 26405106 0 34 theme N-glycan 27:34 arg1 pentasaccharide 41:55 N-glycan core pentasaccharide 27:55 N-glycan core pentasaccharide 27:55 Preferred conformations of N-glycan core pentasaccharide in solution and in glycoproteins. 26405106 4 35 theme conformational 578:591 arg1 variability 593:603 the comparable conformational variability 563:603 the comparable conformational variability of the pentasaccharide in solution 563:638 Both simulations yield the comparable conformational variability of the pentasaccharide in solution, indicating the convergence of both simulations. 26405106 5 36 theme conformational 753:766 arg1 freedom 768:774 the conformational freedom 749:774 the conformational freedom of the N-glycan on the protein surface 749:813 The glycoprotein crystal structures are analyzed to compare the conformational freedom of the N-glycan on the protein surface with the simulation result. 26405106 8 37 theme hydrogen 1303:1310 arg1 bonds 1312:1316 intramolecular hydrogen bonds 1288:1316 intramolecular hydrogen bonds 1288:1316 Finally, the transfer entropy analysis of the simulation trajectory also reveals an unexpected causality relationship between intramolecular hydrogen bonds and the conformational states in that the hydrogen bonds play a role in maintaining the conformational states rather than driving the change in glycosidic torsional states. 26405106 4 38 theme simulations 676:686 arg1 convergence 656:666 the convergence 652:666 the convergence of both simulations 652:686 Both simulations yield the comparable conformational variability of the pentasaccharide in solution, indicating the convergence of both simulations. 26405106 3 39 theme N-glycan 384:391 arg1 moiety 414:419 the N-glycan core pentasaccharide moiety 380:419 the N-glycan core pentasaccharide moiety 380:419 In this work, we have examined the conformational freedom of the N-glycan core pentasaccharide moiety in solution using standard molecular dynamics (MD) simulations as well as temperature replica-exchange MD simulations. 26405106 2 40 theme free 301:304 arg1 glycans 293:299 the same glycans 284:299 the same glycans free in solution 284:316 Such contacts could restrict their conformational freedom compared to the same glycans free in solution. 26405106 8 41 theme torsional 1473:1481 arg1 states 1483:1488 glycosidic torsional states 1462:1488 glycosidic torsional states 1462:1488 Finally, the transfer entropy analysis of the simulation trajectory also reveals an unexpected causality relationship between intramolecular hydrogen bonds and the conformational states in that the hydrogen bonds play a role in maintaining the conformational states rather than driving the change in glycosidic torsional states. 26405106 5 42 theme crystal 706:712 arg1 structures 714:723 The glycoprotein crystal structures 689:723 The glycoprotein crystal structures 689:723 The glycoprotein crystal structures are analyzed to compare the conformational freedom of the N-glycan on the protein surface with the simulation result. 26405106 8 43 theme hydrogen 1360:1367 arg1 bonds 1369:1373 the hydrogen bonds 1356:1373 the hydrogen bonds 1356:1373 Finally, the transfer entropy analysis of the simulation trajectory also reveals an unexpected causality relationship between intramolecular hydrogen bonds and the conformational states in that the hydrogen bonds play a role in maintaining the conformational states rather than driving the change in glycosidic torsional states. 26405106 0 44 theme pentasaccharide 41:55 arg1 conformations 10:22 Preferred conformations 0:22 Preferred conformations of N-glycan core pentasaccharide in solution and in glycoproteins 0:88 Preferred conformations of N-glycan core pentasaccharide in solution and in glycoproteins. 26405106 6 45 from free 877:880 arg1 solution 885:892 solution 885:892 solution 885:892 Surprisingly, the pentasaccharide free in solution shows more restricted conformational variability than the N-glycan on the protein surface. 26405106 3 46 theme MD 468:469 arg1 simulations 472:482 standard molecular dynamics (MD) simulations 439:482 standard molecular dynamics (MD) simulations as well as temperature replica-exchange MD simulations 439:537 In this work, we have examined the conformational freedom of the N-glycan core pentasaccharide moiety in solution using standard molecular dynamics (MD) simulations as well as temperature replica-exchange MD simulations. 26405106 0 47 theme core 36:39 arg1 pentasaccharide 41:55 N-glycan core pentasaccharide 27:55 N-glycan core pentasaccharide 27:55 Preferred conformations of N-glycan core pentasaccharide in solution and in glycoproteins. 26405106 6 48 from solution 885:892 arg1 free 877:880 free 877:880 free 877:880 Surprisingly, the pentasaccharide free in solution shows more restricted conformational variability than the N-glycan on the protein surface. 26405106 3 49 from freedom 369:375 arg1 solution 424:431 solution 424:431 solution 424:431 In this work, we have examined the conformational freedom of the N-glycan core pentasaccharide moiety in solution using standard molecular dynamics (MD) simulations as well as temperature replica-exchange MD simulations. 26405106 2 50 theme conformational 249:262 arg1 freedom 264:270 their conformational freedom 243:270 their conformational freedom 243:270 Such contacts could restrict their conformational freedom compared to the same glycans free in solution. 26405106 7 51 theme increased 1087:1095 arg1 diversity 1112:1120 the increased conformational diversity 1083:1120 the increased conformational diversity of the N-glycan on the protein surface 1083:1159 The interactions between the carbohydrate and the protein side chain appear to be responsible for the increased conformational diversity of the N-glycan on the protein surface. 26405106 4 52 from variability 593:603 arg1 solution 631:638 solution 631:638 solution 631:638 Both simulations yield the comparable conformational variability of the pentasaccharide in solution, indicating the convergence of both simulations. 26405106 3 53 theme moiety 414:419 arg1 freedom 369:375 the conformational freedom 350:375 the conformational freedom of the N-glycan core pentasaccharide moiety in solution 350:431 In this work, we have examined the conformational freedom of the N-glycan core pentasaccharide moiety in solution using standard molecular dynamics (MD) simulations as well as temperature replica-exchange MD simulations. 26405106 8 54 theme entropy 1184:1190 arg1 analysis 1192:1199 the transfer entropy analysis 1171:1199 the transfer entropy analysis of the simulation trajectory 1171:1228 Finally, the transfer entropy analysis of the simulation trajectory also reveals an unexpected causality relationship between intramolecular hydrogen bonds and the conformational states in that the hydrogen bonds play a role in maintaining the conformational states rather than driving the change in glycosidic torsional states. 26405106 6 55 theme conformational 916:929 arg1 variability 931:941 more restricted conformational variability 900:941 more restricted conformational variability 900:941 Surprisingly, the pentasaccharide free in solution shows more restricted conformational variability than the N-glycan on the protein surface. 26405106 7 56 theme conformational 1097:1110 arg1 diversity 1112:1120 the increased conformational diversity 1083:1120 the increased conformational diversity of the N-glycan on the protein surface 1083:1159 The interactions between the carbohydrate and the protein side chain appear to be responsible for the increased conformational diversity of the N-glycan on the protein surface. 26405106 1 57 theme protein 115:121 arg1 surfaces 123:130 protein surfaces 115:130 protein surfaces 115:130 N-linked glycans are on protein surfaces and have direct and water/ion-mediated interactions with surrounding amino acids. 26405106 4 58 theme comparable 567:576 arg1 variability 593:603 the comparable conformational variability 563:603 the comparable conformational variability of the pentasaccharide in solution 563:638 Both simulations yield the comparable conformational variability of the pentasaccharide in solution, indicating the convergence of both simulations. 26405106 7 59 theme protein 1145:1151 arg1 surface 1153:1159 the protein surface 1141:1159 the protein surface 1141:1159 The interactions between the carbohydrate and the protein side chain appear to be responsible for the increased conformational diversity of the N-glycan on the protein surface. 26405106 6 60 theme restricted 905:914 arg1 variability 931:941 more restricted conformational variability 900:941 more restricted conformational variability 900:941 Surprisingly, the pentasaccharide free in solution shows more restricted conformational variability than the N-glycan on the protein surface. 26405106 3 61 theme replica-exchange 507:522 arg1 simulations 527:537 temperature replica-exchange MD simulations 495:537 standard molecular dynamics (MD) simulations as well as temperature replica-exchange MD simulations 439:537 In this work, we have examined the conformational freedom of the N-glycan core pentasaccharide moiety in solution using standard molecular dynamics (MD) simulations as well as temperature replica-exchange MD simulations. 26405106 2 62 from free 301:304 arg1 solution 309:316 solution 309:316 solution 309:316 Such contacts could restrict their conformational freedom compared to the same glycans free in solution. 26405106 2 63 theme same 288:291 arg1 glycans 293:299 the same glycans 284:299 the same glycans free in solution 284:316 Such contacts could restrict their conformational freedom compared to the same glycans free in solution. 26405106 8 64 from change 1452:1457 arg1 states 1483:1488 glycosidic torsional states 1462:1488 glycosidic torsional states 1462:1488 Finally, the transfer entropy analysis of the simulation trajectory also reveals an unexpected causality relationship between intramolecular hydrogen bonds and the conformational states in that the hydrogen bonds play a role in maintaining the conformational states rather than driving the change in glycosidic torsional states. 26405106 7 65 from diversity 1112:1120 arg1 surface 1153:1159 the protein surface 1141:1159 the protein surface 1141:1159 The interactions between the carbohydrate and the protein side chain appear to be responsible for the increased conformational diversity of the N-glycan on the protein surface. 26405106 2 66 theme Such 214:217 arg1 contacts 219:226 Such contacts 214:226 Such contacts 214:226 Such contacts could restrict their conformational freedom compared to the same glycans free in solution. 26405106 2 67 from solution 309:316 arg1 free 301:304 free 301:304 free 301:304 Such contacts could restrict their conformational freedom compared to the same glycans free in solution. 26405106 8 68 theme simulation 1208:1217 arg1 trajectory 1219:1228 the simulation trajectory 1204:1228 the simulation trajectory 1204:1228 Finally, the transfer entropy analysis of the simulation trajectory also reveals an unexpected causality relationship between intramolecular hydrogen bonds and the conformational states in that the hydrogen bonds play a role in maintaining the conformational states rather than driving the change in glycosidic torsional states. 26405106 1 69 theme direct 141:146 arg1 interactions 171:182 direct and water/ion-mediated interactions 141:182 direct and water/ion-mediated interactions with surrounding amino acids 141:211 N-linked glycans are on protein surfaces and have direct and water/ion-mediated interactions with surrounding amino acids. 26405106 5 70 gly glycoprotein 693:704 arg1 glycoprotein 693:704 The glycoprotein crystal structures 689:723 The glycoprotein crystal structures 689:723 The glycoprotein crystal structures are analyzed to compare the conformational freedom of the N-glycan on the protein surface with the simulation result. 26405106 8 71 theme conformational 1326:1339 arg1 states 1341:1346 the conformational states 1322:1346 the conformational states 1322:1346 Finally, the transfer entropy analysis of the simulation trajectory also reveals an unexpected causality relationship between intramolecular hydrogen bonds and the conformational states in that the hydrogen bonds play a role in maintaining the conformational states rather than driving the change in glycosidic torsional states. 26405106 1 72 contain have 136:139 arg2 interactions 171:182 direct and water/ion-mediated interactions 141:182 direct and water/ion-mediated interactions with surrounding amino acids 141:211 N-linked glycans are on protein surfaces and have direct and water/ion-mediated interactions with surrounding amino acids. 26405106 1 72 contain have 136:139 arg1 glycans 100:106 N-linked glycans 91:106 N-linked glycans 91:106 N-linked glycans are on protein surfaces and have direct and water/ion-mediated interactions with surrounding amino acids. 26405106 8 73 theme intramolecular 1288:1301 arg1 bonds 1312:1316 intramolecular hydrogen bonds 1288:1316 intramolecular hydrogen bonds 1288:1316 Finally, the transfer entropy analysis of the simulation trajectory also reveals an unexpected causality relationship between intramolecular hydrogen bonds and the conformational states in that the hydrogen bonds play a role in maintaining the conformational states rather than driving the change in glycosidic torsional states. 26405106 8 74 theme conformational 1406:1419 arg1 states 1421:1426 the conformational states 1402:1426 the conformational states 1402:1426 Finally, the transfer entropy analysis of the simulation trajectory also reveals an unexpected causality relationship between intramolecular hydrogen bonds and the conformational states in that the hydrogen bonds play a role in maintaining the conformational states rather than driving the change in glycosidic torsional states. 25781897 2 0 theme expression 383:392 arg1 effect 329:334 the effect 325:334 the effect of high-level endo-β-N-acetylglucosaminidase H expression in Pichia pastoris 325:411 The present study aimed to assess the effect of high-level endo-β-N-acetylglucosaminidase H expression in Pichia pastoris. 25781897 4 1 theme pHBM905A 591:598 arg1 vector 600:605 a pHBM905A vector 589:605 a pHBM905A vector 589:605 This novel gene was cloned into a pHBM905A vector and introduced into Pichia pastoris GS115 for secretary expression. 25781897 9 2 theme recombinant 1282:1292 arg1 strain 1294:1299 this recombinant strain 1277:1299 this recombinant strain 1277:1299 Moreover, our study showed that the N-linked glycan side-chains of several recombinant proteins expressed in Pichia pastoris can be efficiently removed through either the co-fermentation of this recombinant strain with strains expressing substrates or by mixing the cell culture supernatants of the endo-β-N-acetylglucosaminidase H expressing strain with strains expressing substrates after fermentation. 25781897 2 3 theme H 381:381 arg1 expression 383:392 high-level endo-β-N-acetylglucosaminidase H expression 339:392 high-level endo-β-N-acetylglucosaminidase H expression 339:392 The present study aimed to assess the effect of high-level endo-β-N-acetylglucosaminidase H expression in Pichia pastoris. 25781897 9 4 dep co-fermentation 1258:1272 arg1 either 1247:1252 either 1247:1252 either 1247:1252 Moreover, our study showed that the N-linked glycan side-chains of several recombinant proteins expressed in Pichia pastoris can be efficiently removed through either the co-fermentation of this recombinant strain with strains expressing substrates or by mixing the cell culture supernatants of the endo-β-N-acetylglucosaminidase H expressing strain with strains expressing substrates after fermentation. 25781897 9 5 theme strain 1294:1299 arg1 co-fermentation 1258:1272 either the co-fermentation 1247:1272 co-fermentation 1258:1272 Moreover, our study showed that the N-linked glycan side-chains of several recombinant proteins expressed in Pichia pastoris can be efficiently removed through either the co-fermentation of this recombinant strain with strains expressing substrates or by mixing the cell culture supernatants of the endo-β-N-acetylglucosaminidase H expressing strain with strains expressing substrates after fermentation. 25781897 2 6 from effect 329:334 arg1 pastoris 404:411 Pichia pastoris 397:411 Pichia pastoris 397:411 The present study aimed to assess the effect of high-level endo-β-N-acetylglucosaminidase H expression in Pichia pastoris. 25781897 5 7 theme 6-d 746:748 arg1 induction 750:758 a 6-d induction 744:758 a 6-d induction 744:758 The yield of the target protein reached approximately 397 mg/l after a 6-d induction with 1% (v/v) methanol in shake flasks, which is much higher than that observed upon heterologous expression in Escherichia coli and silkworm. 25781897 5 7 theme 6-d 746:748 arg1 higher 814:819 higher 814:819 higher 814:819 The yield of the target protein reached approximately 397 mg/l after a 6-d induction with 1% (v/v) methanol in shake flasks, which is much higher than that observed upon heterologous expression in Escherichia coli and silkworm. 25781897 0 8 from plicatus 76:83 arg1 expression 11:20 High-level expression 0:20 High-level expression of endo-β-N-acetylglucosaminidase H from Streptomyces plicatus in Pichia pastoris and its application for the deglycosylation of glycoproteins. 0:164 High-level expression of endo-β-N-acetylglucosaminidase H from Streptomyces plicatus in Pichia pastoris and its application for the deglycosylation of glycoproteins. 25781897 8 9 theme optimum 1024:1030 arg1 pH 1032:1033 Its optimum pH 1020:1033 Its optimum pH 1020:1033 Its optimum pH and temperature were pH 5.5 and 37°C, respectively. 25781897 9 10 theme recombinant 1162:1172 arg1 proteins 1174:1181 several recombinant proteins 1154:1181 several recombinant proteins expressed in Pichia pastoris 1154:1210 Moreover, our study showed that the N-linked glycan side-chains of several recombinant proteins expressed in Pichia pastoris can be efficiently removed through either the co-fermentation of this recombinant strain with strains expressing substrates or by mixing the cell culture supernatants of the endo-β-N-acetylglucosaminidase H expressing strain with strains expressing substrates after fermentation. 25781897 2 11 theme present 295:301 arg1 study 303:307 The present study 291:307 The present study 291:307 The present study aimed to assess the effect of high-level endo-β-N-acetylglucosaminidase H expression in Pichia pastoris. 25781897 1 12 theme glycoproteins 276:288 arg1 study 267:271 the study 263:271 the study of glycoproteins 263:288 Endo-β-N-acetylglucosaminidase H (Endo H, EC3.2.1.96) is a glycohydrolase that is widely used in the study of glycoproteins. 25781897 2 13 theme endo-β-N-acetylglucosaminidase 350:379 arg1 expression 383:392 high-level endo-β-N-acetylglucosaminidase H expression 339:392 high-level endo-β-N-acetylglucosaminidase H expression 339:392 The present study aimed to assess the effect of high-level endo-β-N-acetylglucosaminidase H expression in Pichia pastoris. 25781897 10 14 theme first 1504:1508 arg1 report 1510:1515 the first report 1500:1515 the first report of high-level endo-β-N-acetylglucosaminidase H expression in Pichia pastoris 1500:1592 This is the first report of high-level endo-β-N-acetylglucosaminidase H expression in Pichia pastoris and the application of this enzyme in the deglycosylation of raw glycoproteins heterologously expressed in Pichia pastoris using simplified methods. 25781897 10 14 theme first 1504:1508 arg1 This 1492:1495 This 1492:1495 This 1492:1495 This is the first report of high-level endo-β-N-acetylglucosaminidase H expression in Pichia pastoris and the application of this enzyme in the deglycosylation of raw glycoproteins heterologously expressed in Pichia pastoris using simplified methods. 25781897 3 15 theme usage 486:490 arg1 bias 492:495 the codon usage bias 476:495 the codon usage bias of Pichia pastoris 476:514 The DNA coding sequence of this enzyme was optimized based on the codon usage bias of Pichia pastoris and synthesized through overlapping PCR. 25781897 5 16 theme heterologous 845:856 arg1 expression 858:867 heterologous expression 845:867 heterologous expression in Escherichia coli and silkworm 845:900 The yield of the target protein reached approximately 397 mg/l after a 6-d induction with 1% (v/v) methanol in shake flasks, which is much higher than that observed upon heterologous expression in Escherichia coli and silkworm. 25781897 10 17 theme simplified 1723:1732 arg1 methods 1734:1740 simplified methods 1723:1740 simplified methods 1723:1740 This is the first report of high-level endo-β-N-acetylglucosaminidase H expression in Pichia pastoris and the application of this enzyme in the deglycosylation of raw glycoproteins heterologously expressed in Pichia pastoris using simplified methods. 25781897 10 18 theme glycoproteins 1659:1671 arg1 deglycosylation 1636:1650 the deglycosylation 1632:1650 the deglycosylation of raw glycoproteins heterologously expressed in Pichia pastoris using simplified methods 1632:1740 This is the first report of high-level endo-β-N-acetylglucosaminidase H expression in Pichia pastoris and the application of this enzyme in the deglycosylation of raw glycoproteins heterologously expressed in Pichia pastoris using simplified methods. 25781897 9 19 theme strain 1430:1435 arg1 supernatants 1366:1377 the cell culture supernatants 1349:1377 the cell culture supernatants of the endo-β-N-acetylglucosaminidase H expressing strain 1349:1435 Moreover, our study showed that the N-linked glycan side-chains of several recombinant proteins expressed in Pichia pastoris can be efficiently removed through either the co-fermentation of this recombinant strain with strains expressing substrates or by mixing the cell culture supernatants of the endo-β-N-acetylglucosaminidase H expressing strain with strains expressing substrates after fermentation. 25781897 3 20 theme DNA 418:420 arg1 sequence 429:436 The DNA coding sequence 414:436 The DNA coding sequence of this enzyme 414:451 The DNA coding sequence of this enzyme was optimized based on the codon usage bias of Pichia pastoris and synthesized through overlapping PCR. 25781897 3 21 theme Pichia 500:505 arg1 pastoris 507:514 Pichia pastoris 500:514 Pichia pastoris 500:514 The DNA coding sequence of this enzyme was optimized based on the codon usage bias of Pichia pastoris and synthesized through overlapping PCR. 25781897 10 22 theme raw 1655:1657 arg1 glycoproteins 1659:1671 raw glycoproteins 1655:1671 raw glycoproteins heterologously expressed in Pichia pastoris using simplified methods 1655:1740 This is the first report of high-level endo-β-N-acetylglucosaminidase H expression in Pichia pastoris and the application of this enzyme in the deglycosylation of raw glycoproteins heterologously expressed in Pichia pastoris using simplified methods. 25781897 9 23 link N-linked 1123:1130 arg1 side-chains 1139:1149 the N-linked glycan side-chains 1119:1149 the N-linked glycan side-chains of several recombinant proteins expressed in Pichia pastoris 1119:1210 Moreover, our study showed that the N-linked glycan side-chains of several recombinant proteins expressed in Pichia pastoris can be efficiently removed through either the co-fermentation of this recombinant strain with strains expressing substrates or by mixing the cell culture supernatants of the endo-β-N-acetylglucosaminidase H expressing strain with strains expressing substrates after fermentation. 25781897 10 24 theme enzyme 1622:1627 arg1 report 1510:1515 the first report 1500:1515 the first report of high-level endo-β-N-acetylglucosaminidase H expression in Pichia pastoris 1500:1592 This is the first report of high-level endo-β-N-acetylglucosaminidase H expression in Pichia pastoris and the application of this enzyme in the deglycosylation of raw glycoproteins heterologously expressed in Pichia pastoris using simplified methods. 25781897 10 24 theme enzyme 1622:1627 arg1 application 1602:1612 the application 1598:1612 the application of this enzyme 1598:1627 This is the first report of high-level endo-β-N-acetylglucosaminidase H expression in Pichia pastoris and the application of this enzyme in the deglycosylation of raw glycoproteins heterologously expressed in Pichia pastoris using simplified methods. 25781897 10 24 theme enzyme 1622:1627 arg1 This 1492:1495 This 1492:1495 This 1492:1495 This is the first report of high-level endo-β-N-acetylglucosaminidase H expression in Pichia pastoris and the application of this enzyme in the deglycosylation of raw glycoproteins heterologously expressed in Pichia pastoris using simplified methods. 25781897 5 25 theme 1 765:765 arg1 % 766:766 % 766:766 % 766:766 The yield of the target protein reached approximately 397 mg/l after a 6-d induction with 1% (v/v) methanol in shake flasks, which is much higher than that observed upon heterologous expression in Escherichia coli and silkworm. 25781897 3 26 theme enzyme 446:451 arg1 sequence 429:436 The DNA coding sequence 414:436 The DNA coding sequence of this enzyme 414:451 The DNA coding sequence of this enzyme was optimized based on the codon usage bias of Pichia pastoris and synthesized through overlapping PCR. 25781897 0 27 theme High-level 0:9 arg1 expression 11:20 High-level expression 0:20 High-level expression of endo-β-N-acetylglucosaminidase H from Streptomyces plicatus in Pichia pastoris and its application for the deglycosylation of glycoproteins. 0:164 High-level expression of endo-β-N-acetylglucosaminidase H from Streptomyces plicatus in Pichia pastoris and its application for the deglycosylation of glycoproteins. 25781897 10 28 gly glycoproteins 1659:1671 arg1 glycoproteins 1659:1671 raw glycoproteins 1655:1671 raw glycoproteins heterologously expressed in Pichia pastoris using simplified methods 1655:1740 This is the first report of high-level endo-β-N-acetylglucosaminidase H expression in Pichia pastoris and the application of this enzyme in the deglycosylation of raw glycoproteins heterologously expressed in Pichia pastoris using simplified methods. 25781897 1 29 gly glycoproteins 276:288 arg1 glycoproteins 276:288 glycoproteins 276:288 glycoproteins 276:288 Endo-β-N-acetylglucosaminidase H (Endo H, EC3.2.1.96) is a glycohydrolase that is widely used in the study of glycoproteins. 25781897 1 30 dep Endo 200:203 arg1 H 205:205 H 205:205 Endo H 200:205 Endo-β-N-acetylglucosaminidase H (Endo H, EC3.2.1.96) is a glycohydrolase that is widely used in the study of glycoproteins. 25781897 9 31 theme N-linked 1123:1130 arg1 side-chains 1139:1149 the N-linked glycan side-chains 1119:1149 the N-linked glycan side-chains of several recombinant proteins expressed in Pichia pastoris 1119:1210 Moreover, our study showed that the N-linked glycan side-chains of several recombinant proteins expressed in Pichia pastoris can be efficiently removed through either the co-fermentation of this recombinant strain with strains expressing substrates or by mixing the cell culture supernatants of the endo-β-N-acetylglucosaminidase H expressing strain with strains expressing substrates after fermentation. 25781897 0 32 theme endo-β-N-acetylglucosaminidase 25:54 arg1 H 56:56 endo-β-N-acetylglucosaminidase H 25:56 endo-β-N-acetylglucosaminidase H 25:56 High-level expression of endo-β-N-acetylglucosaminidase H from Streptomyces plicatus in Pichia pastoris and its application for the deglycosylation of glycoproteins. 25781897 9 33 theme Pichia 1196:1201 arg1 pastoris 1203:1210 Pichia pastoris 1196:1210 Pichia pastoris 1196:1210 Moreover, our study showed that the N-linked glycan side-chains of several recombinant proteins expressed in Pichia pastoris can be efficiently removed through either the co-fermentation of this recombinant strain with strains expressing substrates or by mixing the cell culture supernatants of the endo-β-N-acetylglucosaminidase H expressing strain with strains expressing substrates after fermentation. 25781897 10 34 theme endo-β-N-acetylglucosaminidase 1531:1560 arg1 expression 1564:1573 high-level endo-β-N-acetylglucosaminidase H expression 1520:1573 high-level endo-β-N-acetylglucosaminidase H expression in Pichia pastoris 1520:1592 This is the first report of high-level endo-β-N-acetylglucosaminidase H expression in Pichia pastoris and the application of this enzyme in the deglycosylation of raw glycoproteins heterologously expressed in Pichia pastoris using simplified methods. 25781897 9 35 theme proteins 1174:1181 arg1 side-chains 1139:1149 the N-linked glycan side-chains 1119:1149 the N-linked glycan side-chains of several recombinant proteins expressed in Pichia pastoris 1119:1210 Moreover, our study showed that the N-linked glycan side-chains of several recombinant proteins expressed in Pichia pastoris can be efficiently removed through either the co-fermentation of this recombinant strain with strains expressing substrates or by mixing the cell culture supernatants of the endo-β-N-acetylglucosaminidase H expressing strain with strains expressing substrates after fermentation. 25781897 3 36 theme codon 480:484 arg1 bias 492:495 the codon usage bias 476:495 the codon usage bias of Pichia pastoris 476:514 The DNA coding sequence of this enzyme was optimized based on the codon usage bias of Pichia pastoris and synthesized through overlapping PCR. 25781897 7 37 theme specific 985:992 arg1 activity 994:1001 Its specific activity 981:1001 Its specific activity 981:1001 Its specific activity was 461573 U/mg. 25781897 6 38 theme enzymatic 948:956 arg1 features 958:965 its enzymatic features 944:965 its enzymatic features 944:965 This recombinant enzyme was purified and its enzymatic features were studied. 25781897 10 39 theme high-level 1520:1529 arg1 expression 1564:1573 high-level endo-β-N-acetylglucosaminidase H expression 1520:1573 high-level endo-β-N-acetylglucosaminidase H expression in Pichia pastoris 1520:1592 This is the first report of high-level endo-β-N-acetylglucosaminidase H expression in Pichia pastoris and the application of this enzyme in the deglycosylation of raw glycoproteins heterologously expressed in Pichia pastoris using simplified methods. 25781897 5 40 from induction 750:758 arg1 flasks 792:797 shake flasks 786:797 shake flasks 786:797 The yield of the target protein reached approximately 397 mg/l after a 6-d induction with 1% (v/v) methanol in shake flasks, which is much higher than that observed upon heterologous expression in Escherichia coli and silkworm. 25781897 1 41 dep H 197:197 arg1 Endo 200:203 Endo 200:203 Endo 200:203 Endo-β-N-acetylglucosaminidase H (Endo H, EC3.2.1.96) is a glycohydrolase that is widely used in the study of glycoproteins. 25781897 1 42 theme Endo-β-N-acetylglucosaminidase 166:195 arg1 H 197:197 Endo-β-N-acetylglucosaminidase H 166:197 Endo-β-N-acetylglucosaminidase H (Endo H, EC3.2.1.96) 166:218 Endo-β-N-acetylglucosaminidase H (Endo H, EC3.2.1.96) is a glycohydrolase that is widely used in the study of glycoproteins. 25781897 1 42 theme Endo-β-N-acetylglucosaminidase 166:195 arg1 glycohydrolase 225:238 a glycohydrolase 223:238 a glycohydrolase that is widely used in the study of glycoproteins 223:288 Endo-β-N-acetylglucosaminidase H (Endo H, EC3.2.1.96) is a glycohydrolase that is widely used in the study of glycoproteins. 25781897 10 43 from expression 1564:1573 arg1 pastoris 1585:1592 Pichia pastoris 1578:1592 Pichia pastoris 1578:1592 This is the first report of high-level endo-β-N-acetylglucosaminidase H expression in Pichia pastoris and the application of this enzyme in the deglycosylation of raw glycoproteins heterologously expressed in Pichia pastoris using simplified methods. 25781897 3 44 theme pastoris 507:514 arg1 bias 492:495 the codon usage bias 476:495 the codon usage bias of Pichia pastoris 476:514 The DNA coding sequence of this enzyme was optimized based on the codon usage bias of Pichia pastoris and synthesized through overlapping PCR. 25781897 10 45 from pastoris 1585:1592 arg1 report 1510:1515 the first report 1500:1515 the first report of high-level endo-β-N-acetylglucosaminidase H expression in Pichia pastoris 1500:1592 This is the first report of high-level endo-β-N-acetylglucosaminidase H expression in Pichia pastoris and the application of this enzyme in the deglycosylation of raw glycoproteins heterologously expressed in Pichia pastoris using simplified methods. 25781897 10 45 from pastoris 1585:1592 arg1 application 1602:1612 the application 1598:1612 the application of this enzyme 1598:1627 This is the first report of high-level endo-β-N-acetylglucosaminidase H expression in Pichia pastoris and the application of this enzyme in the deglycosylation of raw glycoproteins heterologously expressed in Pichia pastoris using simplified methods. 25781897 10 45 from pastoris 1585:1592 arg1 This 1492:1495 This 1492:1495 This 1492:1495 This is the first report of high-level endo-β-N-acetylglucosaminidase H expression in Pichia pastoris and the application of this enzyme in the deglycosylation of raw glycoproteins heterologously expressed in Pichia pastoris using simplified methods. 25781897 5 46 with induction 750:758 arg1 methanol 774:781 1% (v/v) methanol 765:781 1% (v/v) methanol 765:781 The yield of the target protein reached approximately 397 mg/l after a 6-d induction with 1% (v/v) methanol in shake flasks, which is much higher than that observed upon heterologous expression in Escherichia coli and silkworm. 25781897 10 47 theme Pichia 1701:1706 arg1 pastoris 1708:1715 Pichia pastoris 1701:1715 Pichia pastoris using simplified methods 1701:1740 This is the first report of high-level endo-β-N-acetylglucosaminidase H expression in Pichia pastoris and the application of this enzyme in the deglycosylation of raw glycoproteins heterologously expressed in Pichia pastoris using simplified methods. 25781897 0 48 theme H 56:56 arg1 expression 11:20 High-level expression 0:20 High-level expression of endo-β-N-acetylglucosaminidase H from Streptomyces plicatus in Pichia pastoris and its application for the deglycosylation of glycoproteins. 0:164 High-level expression of endo-β-N-acetylglucosaminidase H from Streptomyces plicatus in Pichia pastoris and its application for the deglycosylation of glycoproteins. 25781897 9 49 theme cell 1353:1356 arg1 supernatants 1366:1377 the cell culture supernatants 1349:1377 the cell culture supernatants of the endo-β-N-acetylglucosaminidase H expressing strain 1349:1435 Moreover, our study showed that the N-linked glycan side-chains of several recombinant proteins expressed in Pichia pastoris can be efficiently removed through either the co-fermentation of this recombinant strain with strains expressing substrates or by mixing the cell culture supernatants of the endo-β-N-acetylglucosaminidase H expressing strain with strains expressing substrates after fermentation. 25781897 0 50 theme glycoproteins 151:163 arg1 deglycosylation 132:146 the deglycosylation 128:146 the deglycosylation of glycoproteins 128:163 High-level expression of endo-β-N-acetylglucosaminidase H from Streptomyces plicatus in Pichia pastoris and its application for the deglycosylation of glycoproteins. 25781897 10 51 from application 1602:1612 arg1 pastoris 1585:1592 Pichia pastoris 1578:1592 Pichia pastoris 1578:1592 This is the first report of high-level endo-β-N-acetylglucosaminidase H expression in Pichia pastoris and the application of this enzyme in the deglycosylation of raw glycoproteins heterologously expressed in Pichia pastoris using simplified methods. 25781897 10 51 from application 1602:1612 arg1 deglycosylation 1636:1650 the deglycosylation 1632:1650 the deglycosylation of raw glycoproteins heterologously expressed in Pichia pastoris using simplified methods 1632:1740 This is the first report of high-level endo-β-N-acetylglucosaminidase H expression in Pichia pastoris and the application of this enzyme in the deglycosylation of raw glycoproteins heterologously expressed in Pichia pastoris using simplified methods. 25781897 4 52 theme secretary 653:661 arg1 expression 663:672 secretary expression 653:672 secretary expression 653:672 This novel gene was cloned into a pHBM905A vector and introduced into Pichia pastoris GS115 for secretary expression. 25781897 3 53 theme coding 422:427 arg1 sequence 429:436 The DNA coding sequence 414:436 The DNA coding sequence of this enzyme 414:451 The DNA coding sequence of this enzyme was optimized based on the codon usage bias of Pichia pastoris and synthesized through overlapping PCR. 25781897 9 54 theme culture 1358:1364 arg1 supernatants 1366:1377 the cell culture supernatants 1349:1377 the cell culture supernatants of the endo-β-N-acetylglucosaminidase H expressing strain 1349:1435 Moreover, our study showed that the N-linked glycan side-chains of several recombinant proteins expressed in Pichia pastoris can be efficiently removed through either the co-fermentation of this recombinant strain with strains expressing substrates or by mixing the cell culture supernatants of the endo-β-N-acetylglucosaminidase H expressing strain with strains expressing substrates after fermentation. 25781897 10 55 theme Pichia 1578:1583 arg1 pastoris 1585:1592 Pichia pastoris 1578:1592 Pichia pastoris 1578:1592 This is the first report of high-level endo-β-N-acetylglucosaminidase H expression in Pichia pastoris and the application of this enzyme in the deglycosylation of raw glycoproteins heterologously expressed in Pichia pastoris using simplified methods. 25781897 10 56 theme expression 1564:1573 arg1 report 1510:1515 the first report 1500:1515 the first report of high-level endo-β-N-acetylglucosaminidase H expression in Pichia pastoris 1500:1592 This is the first report of high-level endo-β-N-acetylglucosaminidase H expression in Pichia pastoris and the application of this enzyme in the deglycosylation of raw glycoproteins heterologously expressed in Pichia pastoris using simplified methods. 25781897 10 56 theme expression 1564:1573 arg1 application 1602:1612 the application 1598:1612 the application of this enzyme 1598:1627 This is the first report of high-level endo-β-N-acetylglucosaminidase H expression in Pichia pastoris and the application of this enzyme in the deglycosylation of raw glycoproteins heterologously expressed in Pichia pastoris using simplified methods. 25781897 10 56 theme expression 1564:1573 arg1 This 1492:1495 This 1492:1495 This 1492:1495 This is the first report of high-level endo-β-N-acetylglucosaminidase H expression in Pichia pastoris and the application of this enzyme in the deglycosylation of raw glycoproteins heterologously expressed in Pichia pastoris using simplified methods. 25781897 0 57 gly deglycosylation 132:146 arg1 glycoproteins 151:163 glycoproteins 151:163 glycoproteins 151:163 High-level expression of endo-β-N-acetylglucosaminidase H from Streptomyces plicatus in Pichia pastoris and its application for the deglycosylation of glycoproteins. 25781897 5 58 theme shake 786:790 arg1 flasks 792:797 shake flasks 786:797 shake flasks 786:797 The yield of the target protein reached approximately 397 mg/l after a 6-d induction with 1% (v/v) methanol in shake flasks, which is much higher than that observed upon heterologous expression in Escherichia coli and silkworm. 25781897 4 59 theme novel 562:566 arg1 gene 568:571 This novel gene 557:571 This novel gene 557:571 This novel gene was cloned into a pHBM905A vector and introduced into Pichia pastoris GS115 for secretary expression. 25781897 5 60 theme target 692:697 arg1 protein 699:705 the target protein 688:705 the target protein 688:705 The yield of the target protein reached approximately 397 mg/l after a 6-d induction with 1% (v/v) methanol in shake flasks, which is much higher than that observed upon heterologous expression in Escherichia coli and silkworm. 25781897 2 61 theme high-level 339:348 arg1 expression 383:392 high-level endo-β-N-acetylglucosaminidase H expression 339:392 high-level endo-β-N-acetylglucosaminidase H expression 339:392 The present study aimed to assess the effect of high-level endo-β-N-acetylglucosaminidase H expression in Pichia pastoris. 25781897 5 62 dep % 766:766 arg1 v/v 769:771 v/v 769:771 v/v 769:771 The yield of the target protein reached approximately 397 mg/l after a 6-d induction with 1% (v/v) methanol in shake flasks, which is much higher than that observed upon heterologous expression in Escherichia coli and silkworm. 25781897 10 63 gly deglycosylation 1636:1650 arg1 glycoproteins 1659:1671 raw glycoproteins 1655:1671 raw glycoproteins heterologously expressed in Pichia pastoris using simplified methods 1655:1740 This is the first report of high-level endo-β-N-acetylglucosaminidase H expression in Pichia pastoris and the application of this enzyme in the deglycosylation of raw glycoproteins heterologously expressed in Pichia pastoris using simplified methods. 25781897 5 64 theme protein 699:705 arg1 yield 679:683 The yield 675:683 The yield of the target protein 675:705 The yield of the target protein reached approximately 397 mg/l after a 6-d induction with 1% (v/v) methanol in shake flasks, which is much higher than that observed upon heterologous expression in Escherichia coli and silkworm. 25781897 1 65 used used 255:258 arg2 H 197:197 Endo-β-N-acetylglucosaminidase H 166:197 Endo-β-N-acetylglucosaminidase H (Endo H, EC3.2.1.96) 166:218 Endo-β-N-acetylglucosaminidase H (Endo H, EC3.2.1.96) is a glycohydrolase that is widely used in the study of glycoproteins. 25781897 1 65 used used 255:258 arg2 glycohydrolase 225:238 a glycohydrolase 223:238 a glycohydrolase that is widely used in the study of glycoproteins 223:288 Endo-β-N-acetylglucosaminidase H (Endo H, EC3.2.1.96) is a glycohydrolase that is widely used in the study of glycoproteins. 25781897 9 66 theme several 1154:1160 arg1 proteins 1174:1181 several recombinant proteins 1154:1181 several recombinant proteins expressed in Pichia pastoris 1154:1210 Moreover, our study showed that the N-linked glycan side-chains of several recombinant proteins expressed in Pichia pastoris can be efficiently removed through either the co-fermentation of this recombinant strain with strains expressing substrates or by mixing the cell culture supernatants of the endo-β-N-acetylglucosaminidase H expressing strain with strains expressing substrates after fermentation. 25781897 0 67 gly glycoproteins 151:163 arg1 glycoproteins 151:163 glycoproteins 151:163 glycoproteins 151:163 High-level expression of endo-β-N-acetylglucosaminidase H from Streptomyces plicatus in Pichia pastoris and its application for the deglycosylation of glycoproteins. 25781897 10 68 theme H 1562:1562 arg1 expression 1564:1573 high-level endo-β-N-acetylglucosaminidase H expression 1520:1573 high-level endo-β-N-acetylglucosaminidase H expression in Pichia pastoris 1520:1592 This is the first report of high-level endo-β-N-acetylglucosaminidase H expression in Pichia pastoris and the application of this enzyme in the deglycosylation of raw glycoproteins heterologously expressed in Pichia pastoris using simplified methods. 25781897 0 69 from application 112:122 arg1 expression 11:20 High-level expression 0:20 High-level expression of endo-β-N-acetylglucosaminidase H from Streptomyces plicatus in Pichia pastoris and its application for the deglycosylation of glycoproteins. 0:164 High-level expression of endo-β-N-acetylglucosaminidase H from Streptomyces plicatus in Pichia pastoris and its application for the deglycosylation of glycoproteins. 25781897 9 70 theme endo-β-N-acetylglucosaminidase 1386:1415 arg1 strain 1430:1435 the endo-β-N-acetylglucosaminidase H expressing strain 1382:1435 the endo-β-N-acetylglucosaminidase H expressing strain 1382:1435 Moreover, our study showed that the N-linked glycan side-chains of several recombinant proteins expressed in Pichia pastoris can be efficiently removed through either the co-fermentation of this recombinant strain with strains expressing substrates or by mixing the cell culture supernatants of the endo-β-N-acetylglucosaminidase H expressing strain with strains expressing substrates after fermentation. 25781897 0 71 theme Pichia 88:93 arg1 pastoris 95:102 Pichia pastoris 88:102 Pichia pastoris 88:102 High-level expression of endo-β-N-acetylglucosaminidase H from Streptomyces plicatus in Pichia pastoris and its application for the deglycosylation of glycoproteins. 25781897 5 72 from expression 858:867 arg1 coli 884:887 Escherichia coli 872:887 Escherichia coli 872:887 The yield of the target protein reached approximately 397 mg/l after a 6-d induction with 1% (v/v) methanol in shake flasks, which is much higher than that observed upon heterologous expression in Escherichia coli and silkworm. 25781897 5 72 from expression 858:867 arg1 silkworm 893:900 silkworm 893:900 silkworm 893:900 The yield of the target protein reached approximately 397 mg/l after a 6-d induction with 1% (v/v) methanol in shake flasks, which is much higher than that observed upon heterologous expression in Escherichia coli and silkworm. 25781897 2 73 theme Pichia 397:402 arg1 pastoris 404:411 Pichia pastoris 397:411 Pichia pastoris 397:411 The present study aimed to assess the effect of high-level endo-β-N-acetylglucosaminidase H expression in Pichia pastoris. 25781897 10 74 from report 1510:1515 arg1 pastoris 1585:1592 Pichia pastoris 1578:1592 Pichia pastoris 1578:1592 This is the first report of high-level endo-β-N-acetylglucosaminidase H expression in Pichia pastoris and the application of this enzyme in the deglycosylation of raw glycoproteins heterologously expressed in Pichia pastoris using simplified methods. 25781897 10 74 from report 1510:1515 arg1 deglycosylation 1636:1650 the deglycosylation 1632:1650 the deglycosylation of raw glycoproteins heterologously expressed in Pichia pastoris using simplified methods 1632:1740 This is the first report of high-level endo-β-N-acetylglucosaminidase H expression in Pichia pastoris and the application of this enzyme in the deglycosylation of raw glycoproteins heterologously expressed in Pichia pastoris using simplified methods. 25781897 9 75 theme H 1417:1417 arg1 strain 1430:1435 the endo-β-N-acetylglucosaminidase H expressing strain 1382:1435 the endo-β-N-acetylglucosaminidase H expressing strain 1382:1435 Moreover, our study showed that the N-linked glycan side-chains of several recombinant proteins expressed in Pichia pastoris can be efficiently removed through either the co-fermentation of this recombinant strain with strains expressing substrates or by mixing the cell culture supernatants of the endo-β-N-acetylglucosaminidase H expressing strain with strains expressing substrates after fermentation. 25781897 5 76 theme % 766:766 arg1 methanol 774:781 1% (v/v) methanol 765:781 1% (v/v) methanol 765:781 The yield of the target protein reached approximately 397 mg/l after a 6-d induction with 1% (v/v) methanol in shake flasks, which is much higher than that observed upon heterologous expression in Escherichia coli and silkworm. 25781897 6 77 theme recombinant 908:918 arg1 enzyme 920:925 This recombinant enzyme 903:925 This recombinant enzyme 903:925 This recombinant enzyme was purified and its enzymatic features were studied. 25781897 9 78 theme expressing 1419:1428 arg1 strain 1430:1435 the endo-β-N-acetylglucosaminidase H expressing strain 1382:1435 the endo-β-N-acetylglucosaminidase H expressing strain 1382:1435 Moreover, our study showed that the N-linked glycan side-chains of several recombinant proteins expressed in Pichia pastoris can be efficiently removed through either the co-fermentation of this recombinant strain with strains expressing substrates or by mixing the cell culture supernatants of the endo-β-N-acetylglucosaminidase H expressing strain with strains expressing substrates after fermentation. 25781897 9 79 theme glycan 1132:1137 arg1 side-chains 1139:1149 the N-linked glycan side-chains 1119:1149 the N-linked glycan side-chains of several recombinant proteins expressed in Pichia pastoris 1119:1210 Moreover, our study showed that the N-linked glycan side-chains of several recombinant proteins expressed in Pichia pastoris can be efficiently removed through either the co-fermentation of this recombinant strain with strains expressing substrates or by mixing the cell culture supernatants of the endo-β-N-acetylglucosaminidase H expressing strain with strains expressing substrates after fermentation. 25781897 3 80 theme overlapping 540:550 arg1 PCR 552:554 overlapping PCR 540:554 overlapping PCR 540:554 The DNA coding sequence of this enzyme was optimized based on the codon usage bias of Pichia pastoris and synthesized through overlapping PCR. 25781897 4 81 theme Pichia 627:632 arg1 pastoris 634:641 Pichia pastoris GS115 627:647 Pichia pastoris GS115 for secretary expression 627:672 This novel gene was cloned into a pHBM905A vector and introduced into Pichia pastoris GS115 for secretary expression. 25127151 0 0 theme pharmacophore 81:93 arg1 mapping 95:101 pharmacophore mapping 81:101 pharmacophore mapping from known antibacterial leads 81:132 Extending the N-linked aminopiperidine class to the mycobacterial gyrase domain: pharmacophore mapping from known antibacterial leads. 25127151 3 1 theme molecular 485:493 arg1 strategy 509:516 molecular hybridization strategy 485:516 molecular hybridization strategy 485:516 With this as objective, a series of 1-(2-(4-aminopiperidin-1-yl)ethyl)-1,5-naphthyridin-2(1H)-one derivatives were designed by molecular hybridization strategy and synthesized following nine step reaction to yield activity in low nanomolar range and commendable antibacterial activities. 25127151 4 2 theme 78 nM 812:816 arg1 IC50 804:807 an IC50 801:807 an IC50 of 78 nM against Mycobacterium tuberculosis DNA gyrase enzyme 801:869 Compound 1-(4-fluorophenyl)-3-(1-(2-(7-methoxy-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl)urea (35) emerged as the most promising inhibitor with an IC50 of 78 nM against Mycobacterium tuberculosis DNA gyrase enzyme, with MTB MIC of 0.62 μM, and not cytotoxic at 50 μM in eukaryotic cell line. 25127151 3 3 theme hybridization 495:507 arg1 strategy 509:516 molecular hybridization strategy 485:516 molecular hybridization strategy 485:516 With this as objective, a series of 1-(2-(4-aminopiperidin-1-yl)ethyl)-1,5-naphthyridin-2(1H)-one derivatives were designed by molecular hybridization strategy and synthesized following nine step reaction to yield activity in low nanomolar range and commendable antibacterial activities. 25127151 4 4 theme tuberculosis 840:851 arg1 enzyme 864:869 Mycobacterium tuberculosis DNA gyrase enzyme 826:869 Mycobacterium tuberculosis DNA gyrase enzyme 826:869 Compound 1-(4-fluorophenyl)-3-(1-(2-(7-methoxy-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl)urea (35) emerged as the most promising inhibitor with an IC50 of 78 nM against Mycobacterium tuberculosis DNA gyrase enzyme, with MTB MIC of 0.62 μM, and not cytotoxic at 50 μM in eukaryotic cell line. 25127151 0 5 link N-linked 14:21 arg1 class 39:43 the N-linked aminopiperidine class 10:43 the N-linked aminopiperidine class 10:43 Extending the N-linked aminopiperidine class to the mycobacterial gyrase domain: pharmacophore mapping from known antibacterial leads. 25127151 0 6 dep antibacterial 114:126 arg1 leads 128:132 leads 128:132 leads 128:132 Extending the N-linked aminopiperidine class to the mycobacterial gyrase domain: pharmacophore mapping from known antibacterial leads. 25127151 4 7 theme 0.62 μM 888:894 arg1 MIC 881:883 MTB MIC 877:883 MTB MIC of 0.62 μM 877:894 Compound 1-(4-fluorophenyl)-3-(1-(2-(7-methoxy-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl)urea (35) emerged as the most promising inhibitor with an IC50 of 78 nM against Mycobacterium tuberculosis DNA gyrase enzyme, with MTB MIC of 0.62 μM, and not cytotoxic at 50 μM in eukaryotic cell line. 25127151 4 8 theme Mycobacterium 826:838 arg1 enzyme 864:869 Mycobacterium tuberculosis DNA gyrase enzyme 826:869 Mycobacterium tuberculosis DNA gyrase enzyme 826:869 Compound 1-(4-fluorophenyl)-3-(1-(2-(7-methoxy-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl)urea (35) emerged as the most promising inhibitor with an IC50 of 78 nM against Mycobacterium tuberculosis DNA gyrase enzyme, with MTB MIC of 0.62 μM, and not cytotoxic at 50 μM in eukaryotic cell line. 25127151 3 9 theme step 549:552 arg1 reaction 554:561 nine step reaction 544:561 nine step reaction 544:561 With this as objective, a series of 1-(2-(4-aminopiperidin-1-yl)ethyl)-1,5-naphthyridin-2(1H)-one derivatives were designed by molecular hybridization strategy and synthesized following nine step reaction to yield activity in low nanomolar range and commendable antibacterial activities. 25127151 1 10 theme DNA 145:147 arg1 target 203:208 a well-established and clinically validated target 159:208 a well-established and clinically validated target to develop novel antibacterial 159:239 Bacterial DNA gyrase is a well-established and clinically validated target to develop novel antibacterial. 25127151 1 10 theme DNA 145:147 arg1 gyrase 149:154 Bacterial DNA gyrase 135:154 Bacterial DNA gyrase 135:154 Bacterial DNA gyrase is a well-established and clinically validated target to develop novel antibacterial. 25127151 2 11 theme better 296:301 arg1 compounds 303:311 synthetically better compounds 282:311 synthetically better compounds with possibility of hit to lead development 282:355 Our effort was designated to search for synthetically better compounds with possibility of hit to lead development. 25127151 4 12 from 50 μM 918:922 arg1 line 943:946 eukaryotic cell line 927:946 eukaryotic cell line 927:946 Compound 1-(4-fluorophenyl)-3-(1-(2-(7-methoxy-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl)urea (35) emerged as the most promising inhibitor with an IC50 of 78 nM against Mycobacterium tuberculosis DNA gyrase enzyme, with MTB MIC of 0.62 μM, and not cytotoxic at 50 μM in eukaryotic cell line. 25127151 4 12 from 50 μM 918:922 arg1 cytotoxic 905:913 cytotoxic 905:913 cytotoxic 905:913 Compound 1-(4-fluorophenyl)-3-(1-(2-(7-methoxy-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl)urea (35) emerged as the most promising inhibitor with an IC50 of 78 nM against Mycobacterium tuberculosis DNA gyrase enzyme, with MTB MIC of 0.62 μM, and not cytotoxic at 50 μM in eukaryotic cell line. 25127151 3 13 theme -1,5-naphthyridin-2 428:446 arg1 derivatives 456:466 1-(2-(4-aminopiperidin-1-yl)ethyl)-1,5-naphthyridin-2(1H)-one derivatives 394:466 1-(2-(4-aminopiperidin-1-yl)ethyl)-1,5-naphthyridin-2(1H)-one derivatives 394:466 With this as objective, a series of 1-(2-(4-aminopiperidin-1-yl)ethyl)-1,5-naphthyridin-2(1H)-one derivatives were designed by molecular hybridization strategy and synthesized following nine step reaction to yield activity in low nanomolar range and commendable antibacterial activities. 25127151 1 14 theme validated 193:201 arg1 target 203:208 a well-established and clinically validated target 159:208 a well-established and clinically validated target to develop novel antibacterial 159:239 Bacterial DNA gyrase is a well-established and clinically validated target to develop novel antibacterial. 25127151 1 14 theme validated 193:201 arg1 gyrase 149:154 Bacterial DNA gyrase 135:154 Bacterial DNA gyrase 135:154 Bacterial DNA gyrase is a well-established and clinically validated target to develop novel antibacterial. 25127151 3 15 theme 1- 394:395 arg1 derivatives 456:466 1-(2-(4-aminopiperidin-1-yl)ethyl)-1,5-naphthyridin-2(1H)-one derivatives 394:466 1-(2-(4-aminopiperidin-1-yl)ethyl)-1,5-naphthyridin-2(1H)-one derivatives 394:466 With this as objective, a series of 1-(2-(4-aminopiperidin-1-yl)ethyl)-1,5-naphthyridin-2(1H)-one derivatives were designed by molecular hybridization strategy and synthesized following nine step reaction to yield activity in low nanomolar range and commendable antibacterial activities. 25127151 2 16 theme hit 333:335 arg1 possibility 318:328 possibility 318:328 possibility of hit to lead development 318:355 Our effort was designated to search for synthetically better compounds with possibility of hit to lead development. 25127151 4 17 theme -3- 673:675 arg1 urea 746:749 Compound 1-(4-fluorophenyl)-3-(1-(2-(7-methoxy-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl)urea (35) 646:754 Compound 1-(4-fluorophenyl)-3-(1-(2-(7-methoxy-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl)urea (35) 646:754 Compound 1-(4-fluorophenyl)-3-(1-(2-(7-methoxy-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl)urea (35) emerged as the most promising inhibitor with an IC50 of 78 nM against Mycobacterium tuberculosis DNA gyrase enzyme, with MTB MIC of 0.62 μM, and not cytotoxic at 50 μM in eukaryotic cell line. 25127151 4 17 theme -3- 673:675 arg1 piperidin-4-yl 731:744 1-(2-(7-methoxy-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl 677:744 1-(2-(7-methoxy-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl 677:744 Compound 1-(4-fluorophenyl)-3-(1-(2-(7-methoxy-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl)urea (35) emerged as the most promising inhibitor with an IC50 of 78 nM against Mycobacterium tuberculosis DNA gyrase enzyme, with MTB MIC of 0.62 μM, and not cytotoxic at 50 μM in eukaryotic cell line. 25127151 0 18 theme aminopiperidine 23:37 arg1 class 39:43 the N-linked aminopiperidine class 10:43 the N-linked aminopiperidine class 10:43 Extending the N-linked aminopiperidine class to the mycobacterial gyrase domain: pharmacophore mapping from known antibacterial leads. 25127151 4 19 theme -yl 721:723 arg1 ethyl 725:729 2-(7-methoxy-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl 680:729 2-(7-methoxy-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl 680:729 Compound 1-(4-fluorophenyl)-3-(1-(2-(7-methoxy-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl)urea (35) emerged as the most promising inhibitor with an IC50 of 78 nM against Mycobacterium tuberculosis DNA gyrase enzyme, with MTB MIC of 0.62 μM, and not cytotoxic at 50 μM in eukaryotic cell line. 25127151 4 19 theme -yl 721:723 arg1 1- 677:678 1- 677:678 1- 677:678 Compound 1-(4-fluorophenyl)-3-(1-(2-(7-methoxy-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl)urea (35) emerged as the most promising inhibitor with an IC50 of 78 nM against Mycobacterium tuberculosis DNA gyrase enzyme, with MTB MIC of 0.62 μM, and not cytotoxic at 50 μM in eukaryotic cell line. 25127151 4 20 theme MTB 877:879 arg1 MIC 881:883 MTB MIC 877:883 MTB MIC of 0.62 μM 877:894 Compound 1-(4-fluorophenyl)-3-(1-(2-(7-methoxy-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl)urea (35) emerged as the most promising inhibitor with an IC50 of 78 nM against Mycobacterium tuberculosis DNA gyrase enzyme, with MTB MIC of 0.62 μM, and not cytotoxic at 50 μM in eukaryotic cell line. 25127151 4 21 theme promising 776:784 arg1 inhibitor 786:794 the most promising inhibitor 767:794 the most promising inhibitor with an IC50 of 78 nM against Mycobacterium tuberculosis DNA gyrase enzyme, with MTB MIC of 0.62 μM, and not cytotoxic at 50 μM in eukaryotic cell line 767:946 Compound 1-(4-fluorophenyl)-3-(1-(2-(7-methoxy-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl)urea (35) emerged as the most promising inhibitor with an IC50 of 78 nM against Mycobacterium tuberculosis DNA gyrase enzyme, with MTB MIC of 0.62 μM, and not cytotoxic at 50 μM in eukaryotic cell line. 25127151 4 22 theme Compound 646:653 arg1 urea 746:749 Compound 1-(4-fluorophenyl)-3-(1-(2-(7-methoxy-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl)urea (35) 646:754 Compound 1-(4-fluorophenyl)-3-(1-(2-(7-methoxy-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl)urea (35) 646:754 Compound 1-(4-fluorophenyl)-3-(1-(2-(7-methoxy-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl)urea (35) emerged as the most promising inhibitor with an IC50 of 78 nM against Mycobacterium tuberculosis DNA gyrase enzyme, with MTB MIC of 0.62 μM, and not cytotoxic at 50 μM in eukaryotic cell line. 25127151 4 22 theme Compound 646:653 arg1 piperidin-4-yl 731:744 1-(2-(7-methoxy-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl 677:744 1-(2-(7-methoxy-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl 677:744 Compound 1-(4-fluorophenyl)-3-(1-(2-(7-methoxy-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl)urea (35) emerged as the most promising inhibitor with an IC50 of 78 nM against Mycobacterium tuberculosis DNA gyrase enzyme, with MTB MIC of 0.62 μM, and not cytotoxic at 50 μM in eukaryotic cell line. 25127151 0 23 theme N-linked 14:21 arg1 class 39:43 the N-linked aminopiperidine class 10:43 the N-linked aminopiperidine class 10:43 Extending the N-linked aminopiperidine class to the mycobacterial gyrase domain: pharmacophore mapping from known antibacterial leads. 25127151 1 24 theme well-established 161:176 arg1 target 203:208 a well-established and clinically validated target 159:208 a well-established and clinically validated target to develop novel antibacterial 159:239 Bacterial DNA gyrase is a well-established and clinically validated target to develop novel antibacterial. 25127151 1 24 theme well-established 161:176 arg1 gyrase 149:154 Bacterial DNA gyrase 135:154 Bacterial DNA gyrase 135:154 Bacterial DNA gyrase is a well-established and clinically validated target to develop novel antibacterial. 25127151 3 25 theme -one 451:454 arg1 derivatives 456:466 1-(2-(4-aminopiperidin-1-yl)ethyl)-1,5-naphthyridin-2(1H)-one derivatives 394:466 1-(2-(4-aminopiperidin-1-yl)ethyl)-1,5-naphthyridin-2(1H)-one derivatives 394:466 With this as objective, a series of 1-(2-(4-aminopiperidin-1-yl)ethyl)-1,5-naphthyridin-2(1H)-one derivatives were designed by molecular hybridization strategy and synthesized following nine step reaction to yield activity in low nanomolar range and commendable antibacterial activities. 25127151 4 26 theme cell 938:941 arg1 line 943:946 eukaryotic cell line 927:946 eukaryotic cell line 927:946 Compound 1-(4-fluorophenyl)-3-(1-(2-(7-methoxy-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl)urea (35) emerged as the most promising inhibitor with an IC50 of 78 nM against Mycobacterium tuberculosis DNA gyrase enzyme, with MTB MIC of 0.62 μM, and not cytotoxic at 50 μM in eukaryotic cell line. 25127151 3 27 theme nanomolar 588:596 arg1 range 598:602 low nanomolar range 584:602 low nanomolar range 584:602 With this as objective, a series of 1-(2-(4-aminopiperidin-1-yl)ethyl)-1,5-naphthyridin-2(1H)-one derivatives were designed by molecular hybridization strategy and synthesized following nine step reaction to yield activity in low nanomolar range and commendable antibacterial activities. 25127151 1 28 theme novel 221:225 arg1 antibacterial 227:239 novel antibacterial 221:239 novel antibacterial 221:239 Bacterial DNA gyrase is a well-established and clinically validated target to develop novel antibacterial. 25127151 3 29 theme 4-aminopiperidin-1-yl 400:420 arg1 1- 394:395 1- 394:395 1- 394:395 With this as objective, a series of 1-(2-(4-aminopiperidin-1-yl)ethyl)-1,5-naphthyridin-2(1H)-one derivatives were designed by molecular hybridization strategy and synthesized following nine step reaction to yield activity in low nanomolar range and commendable antibacterial activities. 25127151 3 29 theme 4-aminopiperidin-1-yl 400:420 arg1 ethyl 422:426 2-(4-aminopiperidin-1-yl)ethyl 397:426 2-(4-aminopiperidin-1-yl)ethyl 397:426 With this as objective, a series of 1-(2-(4-aminopiperidin-1-yl)ethyl)-1,5-naphthyridin-2(1H)-one derivatives were designed by molecular hybridization strategy and synthesized following nine step reaction to yield activity in low nanomolar range and commendable antibacterial activities. 25127151 4 30 theme eukaryotic 927:936 arg1 line 943:946 eukaryotic cell line 927:946 eukaryotic cell line 927:946 Compound 1-(4-fluorophenyl)-3-(1-(2-(7-methoxy-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl)urea (35) emerged as the most promising inhibitor with an IC50 of 78 nM against Mycobacterium tuberculosis DNA gyrase enzyme, with MTB MIC of 0.62 μM, and not cytotoxic at 50 μM in eukaryotic cell line. 25127151 3 31 theme 1H 448:449 arg1 derivatives 456:466 1-(2-(4-aminopiperidin-1-yl)ethyl)-1,5-naphthyridin-2(1H)-one derivatives 394:466 1-(2-(4-aminopiperidin-1-yl)ethyl)-1,5-naphthyridin-2(1H)-one derivatives 394:466 With this as objective, a series of 1-(2-(4-aminopiperidin-1-yl)ethyl)-1,5-naphthyridin-2(1H)-one derivatives were designed by molecular hybridization strategy and synthesized following nine step reaction to yield activity in low nanomolar range and commendable antibacterial activities. 25127151 0 32 theme mycobacterial 52:64 arg1 domain 73:78 the mycobacterial gyrase domain 48:78 the mycobacterial gyrase domain 48:78 Extending the N-linked aminopiperidine class to the mycobacterial gyrase domain: pharmacophore mapping from known antibacterial leads. 25127151 4 33 theme gyrase 857:862 arg1 enzyme 864:869 Mycobacterium tuberculosis DNA gyrase enzyme 826:869 Mycobacterium tuberculosis DNA gyrase enzyme 826:869 Compound 1-(4-fluorophenyl)-3-(1-(2-(7-methoxy-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl)urea (35) emerged as the most promising inhibitor with an IC50 of 78 nM against Mycobacterium tuberculosis DNA gyrase enzyme, with MTB MIC of 0.62 μM, and not cytotoxic at 50 μM in eukaryotic cell line. 25127151 4 34 theme DNA 853:855 arg1 enzyme 864:869 Mycobacterium tuberculosis DNA gyrase enzyme 826:869 Mycobacterium tuberculosis DNA gyrase enzyme 826:869 Compound 1-(4-fluorophenyl)-3-(1-(2-(7-methoxy-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl)urea (35) emerged as the most promising inhibitor with an IC50 of 78 nM against Mycobacterium tuberculosis DNA gyrase enzyme, with MTB MIC of 0.62 μM, and not cytotoxic at 50 μM in eukaryotic cell line. 25127151 0 35 from antibacterial 114:126 arg1 mapping 95:101 pharmacophore mapping 81:101 pharmacophore mapping from known antibacterial leads 81:132 Extending the N-linked aminopiperidine class to the mycobacterial gyrase domain: pharmacophore mapping from known antibacterial leads. 25127151 3 36 theme low 584:586 arg1 range 598:602 low nanomolar range 584:602 low nanomolar range 584:602 With this as objective, a series of 1-(2-(4-aminopiperidin-1-yl)ethyl)-1,5-naphthyridin-2(1H)-one derivatives were designed by molecular hybridization strategy and synthesized following nine step reaction to yield activity in low nanomolar range and commendable antibacterial activities. 25127151 3 37 theme commendable 608:618 arg1 activities 634:643 commendable antibacterial activities 608:643 commendable antibacterial activities 608:643 With this as objective, a series of 1-(2-(4-aminopiperidin-1-yl)ethyl)-1,5-naphthyridin-2(1H)-one derivatives were designed by molecular hybridization strategy and synthesized following nine step reaction to yield activity in low nanomolar range and commendable antibacterial activities. 25127151 3 38 theme antibacterial 620:632 arg1 activities 634:643 commendable antibacterial activities 608:643 commendable antibacterial activities 608:643 With this as objective, a series of 1-(2-(4-aminopiperidin-1-yl)ethyl)-1,5-naphthyridin-2(1H)-one derivatives were designed by molecular hybridization strategy and synthesized following nine step reaction to yield activity in low nanomolar range and commendable antibacterial activities. 25127151 1 39 theme Bacterial 135:143 arg1 target 203:208 a well-established and clinically validated target 159:208 a well-established and clinically validated target to develop novel antibacterial 159:239 Bacterial DNA gyrase is a well-established and clinically validated target to develop novel antibacterial. 25127151 1 39 theme Bacterial 135:143 arg1 gyrase 149:154 Bacterial DNA gyrase 135:154 Bacterial DNA gyrase 135:154 Bacterial DNA gyrase is a well-established and clinically validated target to develop novel antibacterial. 25127151 4 40 with inhibitor 786:794 arg1 IC50 804:807 an IC50 801:807 an IC50 of 78 nM against Mycobacterium tuberculosis DNA gyrase enzyme 801:869 Compound 1-(4-fluorophenyl)-3-(1-(2-(7-methoxy-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl)urea (35) emerged as the most promising inhibitor with an IC50 of 78 nM against Mycobacterium tuberculosis DNA gyrase enzyme, with MTB MIC of 0.62 μM, and not cytotoxic at 50 μM in eukaryotic cell line. 25127151 4 40 with inhibitor 786:794 arg1 MIC 881:883 MTB MIC 877:883 MTB MIC of 0.62 μM 877:894 Compound 1-(4-fluorophenyl)-3-(1-(2-(7-methoxy-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl)urea (35) emerged as the most promising inhibitor with an IC50 of 78 nM against Mycobacterium tuberculosis DNA gyrase enzyme, with MTB MIC of 0.62 μM, and not cytotoxic at 50 μM in eukaryotic cell line. 25127151 2 41 theme lead 340:343 arg1 development 345:355 lead development 340:355 lead development 340:355 Our effort was designated to search for synthetically better compounds with possibility of hit to lead development. 25127151 3 42 theme derivatives 456:466 arg1 series 384:389 a series 382:389 a series of 1-(2-(4-aminopiperidin-1-yl)ethyl)-1,5-naphthyridin-2(1H)-one derivatives 382:466 With this as objective, a series of 1-(2-(4-aminopiperidin-1-yl)ethyl)-1,5-naphthyridin-2(1H)-one derivatives were designed by molecular hybridization strategy and synthesized following nine step reaction to yield activity in low nanomolar range and commendable antibacterial activities. 25127151 4 43 theme 4-fluorophenyl 658:671 arg1 urea 746:749 Compound 1-(4-fluorophenyl)-3-(1-(2-(7-methoxy-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl)urea (35) 646:754 Compound 1-(4-fluorophenyl)-3-(1-(2-(7-methoxy-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl)urea (35) 646:754 Compound 1-(4-fluorophenyl)-3-(1-(2-(7-methoxy-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl)urea (35) emerged as the most promising inhibitor with an IC50 of 78 nM against Mycobacterium tuberculosis DNA gyrase enzyme, with MTB MIC of 0.62 μM, and not cytotoxic at 50 μM in eukaryotic cell line. 25127151 4 43 theme 4-fluorophenyl 658:671 arg1 piperidin-4-yl 731:744 1-(2-(7-methoxy-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl 677:744 1-(2-(7-methoxy-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl 677:744 Compound 1-(4-fluorophenyl)-3-(1-(2-(7-methoxy-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl)urea (35) emerged as the most promising inhibitor with an IC50 of 78 nM against Mycobacterium tuberculosis DNA gyrase enzyme, with MTB MIC of 0.62 μM, and not cytotoxic at 50 μM in eukaryotic cell line. 25127151 0 44 theme gyrase 66:71 arg1 domain 73:78 the mycobacterial gyrase domain 48:78 the mycobacterial gyrase domain 48:78 Extending the N-linked aminopiperidine class to the mycobacterial gyrase domain: pharmacophore mapping from known antibacterial leads. 25127151 0 45 dep Extending 0:8 arg1 mapping 95:101 pharmacophore mapping 81:101 pharmacophore mapping from known antibacterial leads 81:132 Extending the N-linked aminopiperidine class to the mycobacterial gyrase domain: pharmacophore mapping from known antibacterial leads. 25127151 4 46 theme 1- 677:678 arg1 urea 746:749 Compound 1-(4-fluorophenyl)-3-(1-(2-(7-methoxy-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl)urea (35) 646:754 Compound 1-(4-fluorophenyl)-3-(1-(2-(7-methoxy-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl)urea (35) 646:754 Compound 1-(4-fluorophenyl)-3-(1-(2-(7-methoxy-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl)urea (35) emerged as the most promising inhibitor with an IC50 of 78 nM against Mycobacterium tuberculosis DNA gyrase enzyme, with MTB MIC of 0.62 μM, and not cytotoxic at 50 μM in eukaryotic cell line. 25127151 4 46 theme 1- 677:678 arg1 piperidin-4-yl 731:744 1-(2-(7-methoxy-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl 677:744 1-(2-(7-methoxy-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl 677:744 Compound 1-(4-fluorophenyl)-3-(1-(2-(7-methoxy-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl)urea (35) emerged as the most promising inhibitor with an IC50 of 78 nM against Mycobacterium tuberculosis DNA gyrase enzyme, with MTB MIC of 0.62 μM, and not cytotoxic at 50 μM in eukaryotic cell line. 25127151 2 47 with compounds 303:311 arg1 possibility 318:328 possibility 318:328 possibility of hit to lead development 318:355 Our effort was designated to search for synthetically better compounds with possibility of hit to lead development. 29192251 0 0 theme respiratory 73:83 arg1 epithelium 85:94 the respiratory epithelium 69:94 the respiratory epithelium 69:94 Access to a main alphaherpesvirus receptor, located basolaterally in the respiratory epithelium, is masked by intercellular junctions. 29192251 8 1 from crucial 1216:1222 arg1 defence 1245:1251 the host's innate defence 1227:1251 the host's innate defence against primary alphaherpesvirus infections 1227:1295 Overall, our findings demonstrate that integrity of the respiratory epithelium is crucial in the host's innate defence against primary alphaherpesvirus infections. 29192251 2 2 theme respiratory 360:370 arg1 epithelium 372:381 the respiratory epithelium 356:381 the respiratory epithelium 356:381 To date, the polarity of alphaherpesvirus infection in the respiratory epithelium and the role of respiratory epithelial integrity herein has not been studied. 29192251 1 3 theme external 253:260 arg1 exposure 262:269 external exposure 253:269 external exposure 253:269 The respiratory epithelium of humans and animals is frequently exposed to alphaherpesviruses, originating from either external exposure or reactivation from latency. 29192251 2 4 theme respiratory 399:409 arg1 integrity 422:430 respiratory epithelial integrity 399:430 respiratory epithelial integrity 399:430 To date, the polarity of alphaherpesvirus infection in the respiratory epithelium and the role of respiratory epithelial integrity herein has not been studied. 29192251 3 5 theme well-known 497:506 arg1 type 480:483 Equine herpesvirus type 1 461:485 Equine herpesvirus type 1 (EHV1) 461:492 Equine herpesvirus type 1 (EHV1), a well-known member of the alphaherpesvirus family, was used to infect equine respiratory mucosal explants and primary equine respiratory epithelial cells (EREC), grown at the air-liquid interface. 29192251 3 5 theme well-known 497:506 arg1 member 508:513 a well-known member 495:513 a well-known member of the alphaherpesvirus family 495:544 Equine herpesvirus type 1 (EHV1), a well-known member of the alphaherpesvirus family, was used to infect equine respiratory mucosal explants and primary equine respiratory epithelial cells (EREC), grown at the air-liquid interface. 29192251 2 6 from polarity 314:321 arg1 epithelium 372:381 the respiratory epithelium 356:381 the respiratory epithelium 356:381 To date, the polarity of alphaherpesvirus infection in the respiratory epithelium and the role of respiratory epithelial integrity herein has not been studied. 29192251 6 7 theme intercellular 1006:1018 arg1 junctions 1020:1028 intercellular junctions 1006:1028 intercellular junctions 1006:1028 Restriction of infection via apical inoculation was overcome by disruption of intercellular junctions. 29192251 3 8 theme herpesvirus 468:478 arg1 member 508:513 a well-known member 495:513 a well-known member of the alphaherpesvirus family 495:544 Equine herpesvirus type 1 (EHV1), a well-known member of the alphaherpesvirus family, was used to infect equine respiratory mucosal explants and primary equine respiratory epithelial cells (EREC), grown at the air-liquid interface. 29192251 3 8 theme herpesvirus 468:478 arg1 type 480:483 Equine herpesvirus type 1 461:485 Equine herpesvirus type 1 (EHV1) 461:492 Equine herpesvirus type 1 (EHV1), a well-known member of the alphaherpesvirus family, was used to infect equine respiratory mucosal explants and primary equine respiratory epithelial cells (EREC), grown at the air-liquid interface. 29192251 3 8 theme herpesvirus 468:478 arg1 EHV1 488:491 EHV1 488:491 EHV1 488:491 Equine herpesvirus type 1 (EHV1), a well-known member of the alphaherpesvirus family, was used to infect equine respiratory mucosal explants and primary equine respiratory epithelial cells (EREC), grown at the air-liquid interface. 29192251 3 9 theme air-liquid 671:680 arg1 interface 682:690 the air-liquid interface 667:690 the air-liquid interface 667:690 Equine herpesvirus type 1 (EHV1), a well-known member of the alphaherpesvirus family, was used to infect equine respiratory mucosal explants and primary equine respiratory epithelial cells (EREC), grown at the air-liquid interface. 29192251 3 10 theme family 539:544 arg1 type 480:483 Equine herpesvirus type 1 461:485 Equine herpesvirus type 1 (EHV1) 461:492 Equine herpesvirus type 1 (EHV1), a well-known member of the alphaherpesvirus family, was used to infect equine respiratory mucosal explants and primary equine respiratory epithelial cells (EREC), grown at the air-liquid interface. 29192251 3 10 theme family 539:544 arg1 member 508:513 a well-known member 495:513 a well-known member of the alphaherpesvirus family 495:544 Equine herpesvirus type 1 (EHV1), a well-known member of the alphaherpesvirus family, was used to infect equine respiratory mucosal explants and primary equine respiratory epithelial cells (EREC), grown at the air-liquid interface. 29192251 9 11 theme defence 1465:1471 arg1 mechanisms 1473:1482 host defence mechanisms 1460:1482 host defence mechanisms 1460:1482 In addition, by targeting a basolaterally located receptor in the respiratory epithelium, alphaherpesviruses have generated a strategy to efficiently escape from host defence mechanisms during reactivation from latency. 29192251 0 12 from located 44:50 arg1 epithelium 85:94 the respiratory epithelium 69:94 the respiratory epithelium 69:94 Access to a main alphaherpesvirus receptor, located basolaterally in the respiratory epithelium, is masked by intercellular junctions. 29192251 8 13 theme respiratory 1190:1200 arg1 epithelium 1202:1211 the respiratory epithelium 1186:1211 the respiratory epithelium 1186:1211 Overall, our findings demonstrate that integrity of the respiratory epithelium is crucial in the host's innate defence against primary alphaherpesvirus infections. 29192251 9 14 theme located 1340:1346 arg1 receptor 1348:1355 a basolaterally located receptor 1324:1355 a basolaterally located receptor in the respiratory epithelium 1324:1385 In addition, by targeting a basolaterally located receptor in the respiratory epithelium, alphaherpesviruses have generated a strategy to efficiently escape from host defence mechanisms during reactivation from latency. 29192251 7 15 theme cellular 1107:1114 arg1 glycans 1125:1131 cellular N-linked glycans 1107:1131 cellular N-linked glycans 1107:1131 Finally, basolateral but not apical EHV1 infection of EREC was dependent on cellular N-linked glycans. 29192251 2 16 from infection 343:351 arg1 epithelium 372:381 the respiratory epithelium 356:381 the respiratory epithelium 356:381 To date, the polarity of alphaherpesvirus infection in the respiratory epithelium and the role of respiratory epithelial integrity herein has not been studied. 29192251 2 17 theme role 391:394 arg1 polarity 314:321 the polarity 310:321 the polarity of alphaherpesvirus infection in the respiratory epithelium and the role of respiratory epithelial integrity 310:430 To date, the polarity of alphaherpesvirus infection in the respiratory epithelium and the role of respiratory epithelial integrity herein has not been studied. 29192251 1 18 theme humans 165:170 arg1 epithelium 151:160 The respiratory epithelium 135:160 The respiratory epithelium of humans and animals 135:182 The respiratory epithelium of humans and animals is frequently exposed to alphaherpesviruses, originating from either external exposure or reactivation from latency. 29192251 5 19 theme basolateral 901:911 arg1 surfaces 918:925 basolateral cell surfaces 901:925 basolateral cell surfaces 901:925 EHV1 preferentially bound to and entered EREC at basolateral cell surfaces. 29192251 6 20 theme junctions 1020:1028 arg1 disruption 992:1001 disruption 992:1001 disruption of intercellular junctions 992:1028 Restriction of infection via apical inoculation was overcome by disruption of intercellular junctions. 29192251 3 21 theme alphaherpesvirus 522:537 arg1 family 539:544 the alphaherpesvirus family 518:544 the alphaherpesvirus family 518:544 Equine herpesvirus type 1 (EHV1), a well-known member of the alphaherpesvirus family, was used to infect equine respiratory mucosal explants and primary equine respiratory epithelial cells (EREC), grown at the air-liquid interface. 29192251 9 22 from receptor 1348:1355 arg1 epithelium 1376:1385 the respiratory epithelium 1360:1385 the respiratory epithelium 1360:1385 In addition, by targeting a basolaterally located receptor in the respiratory epithelium, alphaherpesviruses have generated a strategy to efficiently escape from host defence mechanisms during reactivation from latency. 29192251 8 23 theme epithelium 1202:1211 arg1 integrity 1173:1181 integrity 1173:1181 integrity of the respiratory epithelium 1173:1211 Overall, our findings demonstrate that integrity of the respiratory epithelium is crucial in the host's innate defence against primary alphaherpesvirus infections. 29192251 1 24 theme animals 176:182 arg1 epithelium 151:160 The respiratory epithelium 135:160 The respiratory epithelium of humans and animals 135:182 The respiratory epithelium of humans and animals is frequently exposed to alphaherpesviruses, originating from either external exposure or reactivation from latency. 29192251 7 25 theme N-linked 1116:1123 arg1 glycans 1125:1131 cellular N-linked glycans 1107:1131 cellular N-linked glycans 1107:1131 Finally, basolateral but not apical EHV1 infection of EREC was dependent on cellular N-linked glycans. 29192251 1 26 from latency 292:298 arg1 exposure 262:269 external exposure 253:269 external exposure 253:269 The respiratory epithelium of humans and animals is frequently exposed to alphaherpesviruses, originating from either external exposure or reactivation from latency. 29192251 1 26 from latency 292:298 arg1 reactivation 274:285 reactivation 274:285 reactivation from latency 274:298 The respiratory epithelium of humans and animals is frequently exposed to alphaherpesviruses, originating from either external exposure or reactivation from latency. 29192251 7 27 link N-linked 1116:1123 arg1 glycans 1125:1131 cellular N-linked glycans 1107:1131 cellular N-linked glycans 1107:1131 Finally, basolateral but not apical EHV1 infection of EREC was dependent on cellular N-linked glycans. 29192251 0 28 theme main 12:15 arg1 receptor 34:41 a main alphaherpesvirus receptor 10:41 a main alphaherpesvirus receptor 10:41 Access to a main alphaherpesvirus receptor, located basolaterally in the respiratory epithelium, is masked by intercellular junctions. 29192251 9 29 theme respiratory 1364:1374 arg1 epithelium 1376:1385 the respiratory epithelium 1360:1385 the respiratory epithelium 1360:1385 In addition, by targeting a basolaterally located receptor in the respiratory epithelium, alphaherpesviruses have generated a strategy to efficiently escape from host defence mechanisms during reactivation from latency. 29192251 0 30 theme intercellular 110:122 arg1 junctions 124:132 intercellular junctions 110:132 intercellular junctions 110:132 Access to a main alphaherpesvirus receptor, located basolaterally in the respiratory epithelium, is masked by intercellular junctions. 29192251 2 31 from epithelium 372:381 arg1 polarity 314:321 the polarity 310:321 the polarity of alphaherpesvirus infection in the respiratory epithelium and the role of respiratory epithelial integrity 310:430 To date, the polarity of alphaherpesvirus infection in the respiratory epithelium and the role of respiratory epithelial integrity herein has not been studied. 29192251 4 32 theme explants 734:741 arg1 infection 713:721 and infection 709:721 infection 713:721 EHV1 binding to and infection of mucosal explants was greatly enhanced upon destruction of the respiratory epithelium integrity with EGTA or N-acetylcysteine. 29192251 4 33 theme integrity 811:819 arg1 destruction 769:779 destruction 769:779 destruction of the respiratory epithelium integrity 769:819 EHV1 binding to and infection of mucosal explants was greatly enhanced upon destruction of the respiratory epithelium integrity with EGTA or N-acetylcysteine. 29192251 3 34 used used 551:554 arg2 type 480:483 Equine herpesvirus type 1 461:485 Equine herpesvirus type 1 (EHV1) 461:492 Equine herpesvirus type 1 (EHV1), a well-known member of the alphaherpesvirus family, was used to infect equine respiratory mucosal explants and primary equine respiratory epithelial cells (EREC), grown at the air-liquid interface. 29192251 3 34 used used 551:554 arg2 member 508:513 a well-known member 495:513 a well-known member of the alphaherpesvirus family 495:544 Equine herpesvirus type 1 (EHV1), a well-known member of the alphaherpesvirus family, was used to infect equine respiratory mucosal explants and primary equine respiratory epithelial cells (EREC), grown at the air-liquid interface. 29192251 3 34 used used 551:554 arg2 EHV1 488:491 EHV1 488:491 EHV1 488:491 Equine herpesvirus type 1 (EHV1), a well-known member of the alphaherpesvirus family, was used to infect equine respiratory mucosal explants and primary equine respiratory epithelial cells (EREC), grown at the air-liquid interface. 29192251 4 35 theme mucosal 726:732 arg1 explants 734:741 mucosal explants 726:741 mucosal explants 726:741 EHV1 binding to and infection of mucosal explants was greatly enhanced upon destruction of the respiratory epithelium integrity with EGTA or N-acetylcysteine. 29192251 4 36 theme EHV1 693:696 arg1 binding 698:704 EHV1 binding 693:704 EHV1 binding to and infection of mucosal explants 693:741 EHV1 binding to and infection of mucosal explants was greatly enhanced upon destruction of the respiratory epithelium integrity with EGTA or N-acetylcysteine. 29192251 3 37 theme Equine 461:466 arg1 member 508:513 a well-known member 495:513 a well-known member of the alphaherpesvirus family 495:544 Equine herpesvirus type 1 (EHV1), a well-known member of the alphaherpesvirus family, was used to infect equine respiratory mucosal explants and primary equine respiratory epithelial cells (EREC), grown at the air-liquid interface. 29192251 3 37 theme Equine 461:466 arg1 type 480:483 Equine herpesvirus type 1 461:485 Equine herpesvirus type 1 (EHV1) 461:492 Equine herpesvirus type 1 (EHV1), a well-known member of the alphaherpesvirus family, was used to infect equine respiratory mucosal explants and primary equine respiratory epithelial cells (EREC), grown at the air-liquid interface. 29192251 3 37 theme Equine 461:466 arg1 EHV1 488:491 EHV1 488:491 EHV1 488:491 Equine herpesvirus type 1 (EHV1), a well-known member of the alphaherpesvirus family, was used to infect equine respiratory mucosal explants and primary equine respiratory epithelial cells (EREC), grown at the air-liquid interface. 29192251 3 38 theme mucosal 585:591 arg1 explants 593:600 equine respiratory mucosal explants 566:600 equine respiratory mucosal explants 566:600 Equine herpesvirus type 1 (EHV1), a well-known member of the alphaherpesvirus family, was used to infect equine respiratory mucosal explants and primary equine respiratory epithelial cells (EREC), grown at the air-liquid interface. 29192251 8 39 theme primary 1261:1267 arg1 infections 1286:1295 primary alphaherpesvirus infections 1261:1295 primary alphaherpesvirus infections 1261:1295 Overall, our findings demonstrate that integrity of the respiratory epithelium is crucial in the host's innate defence against primary alphaherpesvirus infections. 29192251 2 40 theme integrity 422:430 arg1 infection 343:351 alphaherpesvirus infection 326:351 alphaherpesvirus infection in the respiratory epithelium 326:381 To date, the polarity of alphaherpesvirus infection in the respiratory epithelium and the role of respiratory epithelial integrity herein has not been studied. 29192251 2 40 theme integrity 422:430 arg1 role 391:394 the role 387:394 the role of respiratory epithelial integrity 387:430 To date, the polarity of alphaherpesvirus infection in the respiratory epithelium and the role of respiratory epithelial integrity herein has not been studied. 29192251 0 41 theme alphaherpesvirus 17:32 arg1 receptor 34:41 a main alphaherpesvirus receptor 10:41 a main alphaherpesvirus receptor 10:41 Access to a main alphaherpesvirus receptor, located basolaterally in the respiratory epithelium, is masked by intercellular junctions. 29192251 6 42 theme apical 957:962 arg1 inoculation 964:974 apical inoculation 957:974 apical inoculation 957:974 Restriction of infection via apical inoculation was overcome by disruption of intercellular junctions. 29192251 9 43 theme host 1460:1463 arg1 mechanisms 1473:1482 host defence mechanisms 1460:1482 host defence mechanisms 1460:1482 In addition, by targeting a basolaterally located receptor in the respiratory epithelium, alphaherpesviruses have generated a strategy to efficiently escape from host defence mechanisms during reactivation from latency. 29192251 3 44 theme epithelial 633:642 arg1 EREC 651:654 EREC 651:654 EREC 651:654 Equine herpesvirus type 1 (EHV1), a well-known member of the alphaherpesvirus family, was used to infect equine respiratory mucosal explants and primary equine respiratory epithelial cells (EREC), grown at the air-liquid interface. 29192251 3 44 theme epithelial 633:642 arg1 cells 644:648 primary equine respiratory epithelial cells 606:648 primary equine respiratory epithelial cells (EREC) 606:655 Equine herpesvirus type 1 (EHV1), a well-known member of the alphaherpesvirus family, was used to infect equine respiratory mucosal explants and primary equine respiratory epithelial cells (EREC), grown at the air-liquid interface. 29192251 4 45 theme epithelium 800:809 arg1 integrity 811:819 the respiratory epithelium integrity 784:819 the respiratory epithelium integrity 784:819 EHV1 binding to and infection of mucosal explants was greatly enhanced upon destruction of the respiratory epithelium integrity with EGTA or N-acetylcysteine. 29192251 2 46 from role 391:394 arg1 epithelium 372:381 the respiratory epithelium 356:381 the respiratory epithelium 356:381 To date, the polarity of alphaherpesvirus infection in the respiratory epithelium and the role of respiratory epithelial integrity herein has not been studied. 29192251 2 47 theme epithelial 411:420 arg1 integrity 422:430 respiratory epithelial integrity 399:430 respiratory epithelial integrity 399:430 To date, the polarity of alphaherpesvirus infection in the respiratory epithelium and the role of respiratory epithelial integrity herein has not been studied. 29192251 0 48 theme located 44:50 arg1 receptor 34:41 a main alphaherpesvirus receptor 10:41 a main alphaherpesvirus receptor 10:41 Access to a main alphaherpesvirus receptor, located basolaterally in the respiratory epithelium, is masked by intercellular junctions. 29192251 7 49 theme EREC 1085:1088 arg1 infection 1072:1080 basolateral but not apical EHV1 infection 1040:1080 basolateral but not apical EHV1 infection of EREC 1040:1088 Finally, basolateral but not apical EHV1 infection of EREC was dependent on cellular N-linked glycans. 29192251 7 50 theme apical 1060:1065 arg1 infection 1072:1080 basolateral but not apical EHV1 infection 1040:1080 basolateral but not apical EHV1 infection of EREC 1040:1088 Finally, basolateral but not apical EHV1 infection of EREC was dependent on cellular N-linked glycans. 29192251 3 51 theme equine 566:571 arg1 explants 593:600 equine respiratory mucosal explants 566:600 equine respiratory mucosal explants 566:600 Equine herpesvirus type 1 (EHV1), a well-known member of the alphaherpesvirus family, was used to infect equine respiratory mucosal explants and primary equine respiratory epithelial cells (EREC), grown at the air-liquid interface. 29192251 7 52 theme basolateral 1040:1050 arg1 infection 1072:1080 basolateral but not apical EHV1 infection 1040:1080 basolateral but not apical EHV1 infection of EREC 1040:1088 Finally, basolateral but not apical EHV1 infection of EREC was dependent on cellular N-linked glycans. 29192251 5 53 theme cell 913:916 arg1 surfaces 918:925 basolateral cell surfaces 901:925 basolateral cell surfaces 901:925 EHV1 preferentially bound to and entered EREC at basolateral cell surfaces. 29192251 6 54 theme infection 943:951 arg1 Restriction 928:938 Restriction 928:938 Restriction of infection via apical inoculation 928:974 Restriction of infection via apical inoculation was overcome by disruption of intercellular junctions. 29192251 7 55 theme EHV1 1067:1070 arg1 infection 1072:1080 basolateral but not apical EHV1 infection 1040:1080 basolateral but not apical EHV1 infection of EREC 1040:1088 Finally, basolateral but not apical EHV1 infection of EREC was dependent on cellular N-linked glycans. 29192251 3 56 theme respiratory 573:583 arg1 explants 593:600 equine respiratory mucosal explants 566:600 equine respiratory mucosal explants 566:600 Equine herpesvirus type 1 (EHV1), a well-known member of the alphaherpesvirus family, was used to infect equine respiratory mucosal explants and primary equine respiratory epithelial cells (EREC), grown at the air-liquid interface. 29192251 2 57 theme infection 343:351 arg1 polarity 314:321 the polarity 310:321 the polarity of alphaherpesvirus infection in the respiratory epithelium and the role of respiratory epithelial integrity 310:430 To date, the polarity of alphaherpesvirus infection in the respiratory epithelium and the role of respiratory epithelial integrity herein has not been studied. 29192251 3 58 theme equine 614:619 arg1 EREC 651:654 EREC 651:654 EREC 651:654 Equine herpesvirus type 1 (EHV1), a well-known member of the alphaherpesvirus family, was used to infect equine respiratory mucosal explants and primary equine respiratory epithelial cells (EREC), grown at the air-liquid interface. 29192251 3 58 theme equine 614:619 arg1 cells 644:648 primary equine respiratory epithelial cells 606:648 primary equine respiratory epithelial cells (EREC) 606:655 Equine herpesvirus type 1 (EHV1), a well-known member of the alphaherpesvirus family, was used to infect equine respiratory mucosal explants and primary equine respiratory epithelial cells (EREC), grown at the air-liquid interface. 29192251 8 59 theme alphaherpesvirus 1269:1284 arg1 infections 1286:1295 primary alphaherpesvirus infections 1261:1295 primary alphaherpesvirus infections 1261:1295 Overall, our findings demonstrate that integrity of the respiratory epithelium is crucial in the host's innate defence against primary alphaherpesvirus infections. 29192251 2 60 theme alphaherpesvirus 326:341 arg1 infection 343:351 alphaherpesvirus infection 326:351 alphaherpesvirus infection in the respiratory epithelium 326:381 To date, the polarity of alphaherpesvirus infection in the respiratory epithelium and the role of respiratory epithelial integrity herein has not been studied. 29192251 8 61 from defence 1245:1251 arg1 crucial 1216:1222 crucial 1216:1222 crucial 1216:1222 Overall, our findings demonstrate that integrity of the respiratory epithelium is crucial in the host's innate defence against primary alphaherpesvirus infections. 29192251 3 62 theme respiratory 621:631 arg1 EREC 651:654 EREC 651:654 EREC 651:654 Equine herpesvirus type 1 (EHV1), a well-known member of the alphaherpesvirus family, was used to infect equine respiratory mucosal explants and primary equine respiratory epithelial cells (EREC), grown at the air-liquid interface. 29192251 3 62 theme respiratory 621:631 arg1 cells 644:648 primary equine respiratory epithelial cells 606:648 primary equine respiratory epithelial cells (EREC) 606:655 Equine herpesvirus type 1 (EHV1), a well-known member of the alphaherpesvirus family, was used to infect equine respiratory mucosal explants and primary equine respiratory epithelial cells (EREC), grown at the air-liquid interface. 29192251 0 63 from epithelium 85:94 arg1 located 44:50 located 44:50 located 44:50 Access to a main alphaherpesvirus receptor, located basolaterally in the respiratory epithelium, is masked by intercellular junctions. 29192251 4 64 theme respiratory 788:798 arg1 integrity 811:819 the respiratory epithelium integrity 784:819 the respiratory epithelium integrity 784:819 EHV1 binding to and infection of mucosal explants was greatly enhanced upon destruction of the respiratory epithelium integrity with EGTA or N-acetylcysteine. 29192251 9 65 from latency 1509:1515 arg1 reactivation 1491:1502 reactivation 1491:1502 reactivation from latency 1491:1515 In addition, by targeting a basolaterally located receptor in the respiratory epithelium, alphaherpesviruses have generated a strategy to efficiently escape from host defence mechanisms during reactivation from latency. 29192251 8 66 theme innate 1238:1243 arg1 defence 1245:1251 the host's innate defence 1227:1251 the host's innate defence against primary alphaherpesvirus infections 1227:1295 Overall, our findings demonstrate that integrity of the respiratory epithelium is crucial in the host's innate defence against primary alphaherpesvirus infections. 29192251 3 67 theme primary 606:612 arg1 EREC 651:654 EREC 651:654 EREC 651:654 Equine herpesvirus type 1 (EHV1), a well-known member of the alphaherpesvirus family, was used to infect equine respiratory mucosal explants and primary equine respiratory epithelial cells (EREC), grown at the air-liquid interface. 29192251 3 67 theme primary 606:612 arg1 cells 644:648 primary equine respiratory epithelial cells 606:648 primary equine respiratory epithelial cells (EREC) 606:655 Equine herpesvirus type 1 (EHV1), a well-known member of the alphaherpesvirus family, was used to infect equine respiratory mucosal explants and primary equine respiratory epithelial cells (EREC), grown at the air-liquid interface. 29192251 1 68 theme respiratory 139:149 arg1 epithelium 151:160 The respiratory epithelium 135:160 The respiratory epithelium of humans and animals 135:182 The respiratory epithelium of humans and animals is frequently exposed to alphaherpesviruses, originating from either external exposure or reactivation from latency. 28687228 0 0 with ureas 31:35 arg1 thiourea 42:49 thiourea 42:49 thiourea 42:49 Effect of replacing main-chain ureas with thiourea and guanidinium surrogates on the bactericidal activity of membrane active oligourea foldamers. 28687228 4 1 theme anthracis 891:899 arg1 forms 879:883 different bacterial forms 859:883 different bacterial forms of B. anthracis (germinated spores and encapsulated bacilli) 859:944 A series of analogues in which urea linkages at selected positions are replaced by thiourea and guanidium surrogates have been prepared on solid support and tested against different bacterial forms of B. anthracis (germinated spores and encapsulated bacilli). 28687228 3 2 theme site-selective 508:521 arg1 modifications 532:544 site-selective chemical modifications 508:544 site-selective chemical modifications of the oligourea backbone 508:570 Here we have used site-selective chemical modifications of the oligourea backbone to gain additional insight into the relationship between structure and function and modulate anthracidal activity. 28687228 0 3 from Effect 0:5 arg1 activity 98:105 the bactericidal activity 81:105 the bactericidal activity of membrane active oligourea 81:134 Effect of replacing main-chain ureas with thiourea and guanidinium surrogates on the bactericidal activity of membrane active oligourea foldamers. 28687228 3 4 theme chemical 523:530 arg1 modifications 532:544 site-selective chemical modifications 508:544 site-selective chemical modifications of the oligourea backbone 508:570 Here we have used site-selective chemical modifications of the oligourea backbone to gain additional insight into the relationship between structure and function and modulate anthracidal activity. 28687228 3 5 theme oligourea 553:561 arg1 backbone 563:570 the oligourea backbone 549:570 the oligourea backbone 549:570 Here we have used site-selective chemical modifications of the oligourea backbone to gain additional insight into the relationship between structure and function and modulate anthracidal activity. 28687228 5 6 theme dipole 1034:1039 arg1 end 1017:1019 the negative end 1004:1019 the negative end of the helix dipole 1004:1039 Urea→thiourea and urea→guanidinium replacements close to the negative end of the helix dipole led to analogues with increased potency and selectivity for B. anthracis versus mammalian cells. 28687228 0 7 theme bactericidal 85:96 arg1 activity 98:105 the bactericidal activity 81:105 the bactericidal activity of membrane active oligourea 81:134 Effect of replacing main-chain ureas with thiourea and guanidinium surrogates on the bactericidal activity of membrane active oligourea foldamers. 28687228 4 8 theme guanidium 783:791 arg1 surrogates 793:802 guanidium surrogates 783:802 guanidium surrogates 783:802 A series of analogues in which urea linkages at selected positions are replaced by thiourea and guanidium surrogates have been prepared on solid support and tested against different bacterial forms of B. anthracis (germinated spores and encapsulated bacilli). 28687228 0 9 with surrogates 67:76 arg1 thiourea 42:49 thiourea 42:49 thiourea 42:49 Effect of replacing main-chain ureas with thiourea and guanidinium surrogates on the bactericidal activity of membrane active oligourea foldamers. 28687228 3 10 theme backbone 563:570 arg1 modifications 532:544 site-selective chemical modifications 508:544 site-selective chemical modifications of the oligourea backbone 508:570 Here we have used site-selective chemical modifications of the oligourea backbone to gain additional insight into the relationship between structure and function and modulate anthracidal activity. 28687228 0 11 theme membrane 110:117 arg1 oligourea 126:134 membrane active oligourea 110:134 membrane active oligourea 110:134 Effect of replacing main-chain ureas with thiourea and guanidinium surrogates on the bactericidal activity of membrane active oligourea foldamers. 28687228 4 12 theme analogues 699:707 arg1 series 689:694 A series 687:694 A series of analogues in which urea linkages at selected positions are replaced by thiourea 687:777 A series of analogues in which urea linkages at selected positions are replaced by thiourea and guanidium surrogates have been prepared on solid support and tested against different bacterial forms of B. anthracis (germinated spores and encapsulated bacilli). 28687228 4 12 theme analogues 699:707 arg1 surrogates 793:802 guanidium surrogates 783:802 guanidium surrogates 783:802 A series of analogues in which urea linkages at selected positions are replaced by thiourea and guanidium surrogates have been prepared on solid support and tested against different bacterial forms of B. anthracis (germinated spores and encapsulated bacilli). 28687228 4 13 theme bacterial 869:877 arg1 forms 879:883 different bacterial forms 859:883 different bacterial forms of B. anthracis (germinated spores and encapsulated bacilli) 859:944 A series of analogues in which urea linkages at selected positions are replaced by thiourea and guanidium surrogates have been prepared on solid support and tested against different bacterial forms of B. anthracis (germinated spores and encapsulated bacilli). 28687228 2 14 theme N'-linked 280:288 arg1 class 314:318 one such class 305:318 one such class of AMP mimics with activities in vitro against a broad range of bacteria including Bacillus anthracis, a Gram-positive sporulating bacillus and causing agent of anthrax 305:487 Amphiphilic cationic helical N,N'-linked oligoureas are one such class of AMP mimics with activities in vitro against a broad range of bacteria including Bacillus anthracis, a Gram-positive sporulating bacillus and causing agent of anthrax. 28687228 2 14 theme N'-linked 280:288 arg1 oligoureas 290:299 Amphiphilic cationic helical N,N'-linked oligoureas 249:299 oligoureas 290:299 Amphiphilic cationic helical N,N'-linked oligoureas are one such class of AMP mimics with activities in vitro against a broad range of bacteria including Bacillus anthracis, a Gram-positive sporulating bacillus and causing agent of anthrax. 28687228 2 15 theme bacteria 384:391 arg1 range 375:379 a broad range 367:379 a broad range of bacteria including Bacillus anthracis, a Gram-positive sporulating bacillus and causing agent of anthrax 367:487 Amphiphilic cationic helical N,N'-linked oligoureas are one such class of AMP mimics with activities in vitro against a broad range of bacteria including Bacillus anthracis, a Gram-positive sporulating bacillus and causing agent of anthrax. 28687228 4 16 theme B. 888:889 arg1 anthracis 891:899 B. anthracis 888:899 B. anthracis (germinated spores and encapsulated bacilli) 888:944 A series of analogues in which urea linkages at selected positions are replaced by thiourea and guanidium surrogates have been prepared on solid support and tested against different bacterial forms of B. anthracis (germinated spores and encapsulated bacilli). 28687228 3 17 theme additional 580:589 arg1 insight 591:597 additional insight 580:597 additional insight into the relationship between structure and function 580:650 Here we have used site-selective chemical modifications of the oligourea backbone to gain additional insight into the relationship between structure and function and modulate anthracidal activity. 28687228 1 18 theme potential 198:206 arg1 mimics 208:213 potential mimics 198:213 potential mimics of antimicrobial peptides (AMPs) 198:246 Membrane-active foldamers have recently emerged as potential mimics of antimicrobial peptides (AMPs). 28687228 4 19 theme urea 718:721 arg1 linkages 723:730 urea linkages 718:730 urea linkages at selected positions 718:752 A series of analogues in which urea linkages at selected positions are replaced by thiourea and guanidium surrogates have been prepared on solid support and tested against different bacterial forms of B. anthracis (germinated spores and encapsulated bacilli). 28687228 0 20 theme main-chain 20:29 arg1 ureas 31:35 replacing main-chain ureas 10:35 replacing main-chain ureas with thiourea 10:49 Effect of replacing main-chain ureas with thiourea and guanidinium surrogates on the bactericidal activity of membrane active oligourea foldamers. 28687228 2 21 link N'-linked 280:288 arg1 class 314:318 one such class 305:318 one such class of AMP mimics with activities in vitro against a broad range of bacteria including Bacillus anthracis, a Gram-positive sporulating bacillus and causing agent of anthrax 305:487 Amphiphilic cationic helical N,N'-linked oligoureas are one such class of AMP mimics with activities in vitro against a broad range of bacteria including Bacillus anthracis, a Gram-positive sporulating bacillus and causing agent of anthrax. 28687228 2 21 link N'-linked 280:288 arg1 oligoureas 290:299 Amphiphilic cationic helical N,N'-linked oligoureas 249:299 oligoureas 290:299 Amphiphilic cationic helical N,N'-linked oligoureas are one such class of AMP mimics with activities in vitro against a broad range of bacteria including Bacillus anthracis, a Gram-positive sporulating bacillus and causing agent of anthrax. 28687228 0 22 theme oligourea 126:134 arg1 activity 98:105 the bactericidal activity 81:105 the bactericidal activity of membrane active oligourea 81:134 Effect of replacing main-chain ureas with thiourea and guanidinium surrogates on the bactericidal activity of membrane active oligourea foldamers. 28687228 5 23 theme negative 1008:1015 arg1 end 1017:1019 the negative end 1004:1019 the negative end of the helix dipole 1004:1039 Urea→thiourea and urea→guanidinium replacements close to the negative end of the helix dipole led to analogues with increased potency and selectivity for B. anthracis versus mammalian cells. 28687228 0 24 theme replacing 10:18 arg1 ureas 31:35 replacing main-chain ureas 10:35 replacing main-chain ureas with thiourea 10:49 Effect of replacing main-chain ureas with thiourea and guanidinium surrogates on the bactericidal activity of membrane active oligourea foldamers. 28687228 0 25 theme active 119:124 arg1 oligourea 126:134 membrane active oligourea 110:134 membrane active oligourea 110:134 Effect of replacing main-chain ureas with thiourea and guanidinium surrogates on the bactericidal activity of membrane active oligourea foldamers. 28687228 2 26 theme such 309:312 arg1 class 314:318 one such class 305:318 one such class of AMP mimics with activities in vitro against a broad range of bacteria including Bacillus anthracis, a Gram-positive sporulating bacillus and causing agent of anthrax 305:487 Amphiphilic cationic helical N,N'-linked oligoureas are one such class of AMP mimics with activities in vitro against a broad range of bacteria including Bacillus anthracis, a Gram-positive sporulating bacillus and causing agent of anthrax. 28687228 2 26 theme such 309:312 arg1 oligoureas 290:299 Amphiphilic cationic helical N,N'-linked oligoureas 249:299 oligoureas 290:299 Amphiphilic cationic helical N,N'-linked oligoureas are one such class of AMP mimics with activities in vitro against a broad range of bacteria including Bacillus anthracis, a Gram-positive sporulating bacillus and causing agent of anthrax. 28687228 5 27 theme increased 1063:1071 arg1 potency 1073:1079 potency 1073:1079 potency 1073:1079 Urea→thiourea and urea→guanidinium replacements close to the negative end of the helix dipole led to analogues with increased potency and selectivity for B. anthracis versus mammalian cells. 28687228 1 28 theme antimicrobial 218:230 arg1 AMPs 242:245 AMPs 242:245 AMPs 242:245 Membrane-active foldamers have recently emerged as potential mimics of antimicrobial peptides (AMPs). 28687228 1 28 theme antimicrobial 218:230 arg1 peptides 232:239 antimicrobial peptides 218:239 antimicrobial peptides (AMPs) 218:246 Membrane-active foldamers have recently emerged as potential mimics of antimicrobial peptides (AMPs). 28687228 2 29 theme anthrax 481:487 arg1 agent 472:476 agent 472:476 agent of anthrax 472:487 Amphiphilic cationic helical N,N'-linked oligoureas are one such class of AMP mimics with activities in vitro against a broad range of bacteria including Bacillus anthracis, a Gram-positive sporulating bacillus and causing agent of anthrax. 28687228 5 30 with analogues 1048:1056 arg1 selectivity 1085:1095 selectivity 1085:1095 selectivity 1085:1095 Urea→thiourea and urea→guanidinium replacements close to the negative end of the helix dipole led to analogues with increased potency and selectivity for B. anthracis versus mammalian cells. 28687228 5 30 with analogues 1048:1056 arg1 potency 1073:1079 potency 1073:1079 potency 1073:1079 Urea→thiourea and urea→guanidinium replacements close to the negative end of the helix dipole led to analogues with increased potency and selectivity for B. anthracis versus mammalian cells. 28687228 2 31 theme Amphiphilic 249:259 arg1 class 314:318 one such class 305:318 one such class of AMP mimics with activities in vitro against a broad range of bacteria including Bacillus anthracis, a Gram-positive sporulating bacillus and causing agent of anthrax 305:487 Amphiphilic cationic helical N,N'-linked oligoureas are one such class of AMP mimics with activities in vitro against a broad range of bacteria including Bacillus anthracis, a Gram-positive sporulating bacillus and causing agent of anthrax. 28687228 2 31 theme Amphiphilic 249:259 arg1 oligoureas 290:299 Amphiphilic cationic helical N,N'-linked oligoureas 249:299 oligoureas 290:299 Amphiphilic cationic helical N,N'-linked oligoureas are one such class of AMP mimics with activities in vitro against a broad range of bacteria including Bacillus anthracis, a Gram-positive sporulating bacillus and causing agent of anthrax. 28687228 1 32 theme peptides 232:239 arg1 mimics 208:213 potential mimics 198:213 potential mimics of antimicrobial peptides (AMPs) 198:246 Membrane-active foldamers have recently emerged as potential mimics of antimicrobial peptides (AMPs). 28687228 0 33 theme ureas 31:35 arg1 Effect 0:5 Effect 0:5 Effect of replacing main-chain ureas with thiourea and guanidinium surrogates on the bactericidal activity of membrane active oligourea 0:134 Effect of replacing main-chain ureas with thiourea and guanidinium surrogates on the bactericidal activity of membrane active oligourea foldamers. 28687228 5 34 theme mammalian 1121:1129 arg1 cells 1131:1135 mammalian cells 1121:1135 mammalian cells 1121:1135 Urea→thiourea and urea→guanidinium replacements close to the negative end of the helix dipole led to analogues with increased potency and selectivity for B. anthracis versus mammalian cells. 28687228 4 35 theme encapsulated 924:935 arg1 bacilli 937:943 encapsulated bacilli 924:943 encapsulated bacilli 924:943 A series of analogues in which urea linkages at selected positions are replaced by thiourea and guanidium surrogates have been prepared on solid support and tested against different bacterial forms of B. anthracis (germinated spores and encapsulated bacilli). 28687228 3 36 theme anthracidal 665:675 arg1 activity 677:684 anthracidal activity 665:684 anthracidal activity 665:684 Here we have used site-selective chemical modifications of the oligourea backbone to gain additional insight into the relationship between structure and function and modulate anthracidal activity. 28687228 4 37 theme different 859:867 arg1 forms 879:883 different bacterial forms 859:883 different bacterial forms of B. anthracis (germinated spores and encapsulated bacilli) 859:944 A series of analogues in which urea linkages at selected positions are replaced by thiourea and guanidium surrogates have been prepared on solid support and tested against different bacterial forms of B. anthracis (germinated spores and encapsulated bacilli). 28687228 4 38 theme selected 735:742 arg1 positions 744:752 selected positions 735:752 selected positions 735:752 A series of analogues in which urea linkages at selected positions are replaced by thiourea and guanidium surrogates have been prepared on solid support and tested against different bacterial forms of B. anthracis (germinated spores and encapsulated bacilli). 28687228 4 39 dep anthracis 891:899 arg1 bacilli 937:943 encapsulated bacilli 924:943 encapsulated bacilli 924:943 A series of analogues in which urea linkages at selected positions are replaced by thiourea and guanidium surrogates have been prepared on solid support and tested against different bacterial forms of B. anthracis (germinated spores and encapsulated bacilli). 28687228 4 39 dep anthracis 891:899 arg1 spores 913:918 germinated spores 902:918 germinated spores 902:918 A series of analogues in which urea linkages at selected positions are replaced by thiourea and guanidium surrogates have been prepared on solid support and tested against different bacterial forms of B. anthracis (germinated spores and encapsulated bacilli). 28687228 5 40 theme Urea→thiourea 947:959 arg1 replacements 982:993 Urea→thiourea and urea→guanidinium replacements 947:993 replacements 982:993 Urea→thiourea and urea→guanidinium replacements close to the negative end of the helix dipole led to analogues with increased potency and selectivity for B. anthracis versus mammalian cells. 28687228 4 41 theme solid 826:830 arg1 support 832:838 solid support 826:838 solid support 826:838 A series of analogues in which urea linkages at selected positions are replaced by thiourea and guanidium surrogates have been prepared on solid support and tested against different bacterial forms of B. anthracis (germinated spores and encapsulated bacilli). 28687228 2 42 dep bacteria 384:391 arg1 including 393:401 including 393:401 including Bacillus anthracis, a Gram-positive sporulating bacillus 393:458 Amphiphilic cationic helical N,N'-linked oligoureas are one such class of AMP mimics with activities in vitro against a broad range of bacteria including Bacillus anthracis, a Gram-positive sporulating bacillus and causing agent of anthrax. 28687228 2 42 dep bacteria 384:391 arg1 causing 464:470 causing 464:470 causing agent of anthrax 464:487 Amphiphilic cationic helical N,N'-linked oligoureas are one such class of AMP mimics with activities in vitro against a broad range of bacteria including Bacillus anthracis, a Gram-positive sporulating bacillus and causing agent of anthrax. 28687228 1 43 theme Membrane-active 147:161 arg1 foldamers 163:171 Membrane-active foldamers 147:171 Membrane-active foldamers 147:171 Membrane-active foldamers have recently emerged as potential mimics of antimicrobial peptides (AMPs). 28687228 5 44 theme helix 1028:1032 arg1 dipole 1034:1039 the helix dipole 1024:1039 the helix dipole 1024:1039 Urea→thiourea and urea→guanidinium replacements close to the negative end of the helix dipole led to analogues with increased potency and selectivity for B. anthracis versus mammalian cells. 28687228 4 45 from positions 744:752 arg1 linkages 723:730 urea linkages 718:730 urea linkages at selected positions 718:752 A series of analogues in which urea linkages at selected positions are replaced by thiourea and guanidium surrogates have been prepared on solid support and tested against different bacterial forms of B. anthracis (germinated spores and encapsulated bacilli). 28687228 3 46 used used 503:506 arg2 we 495:496 we 495:496 we 495:496 Here we have used site-selective chemical modifications of the oligourea backbone to gain additional insight into the relationship between structure and function and modulate anthracidal activity. 28687228 2 47 theme N 278:278 arg1 class 314:318 one such class 305:318 one such class of AMP mimics with activities in vitro against a broad range of bacteria including Bacillus anthracis, a Gram-positive sporulating bacillus and causing agent of anthrax 305:487 Amphiphilic cationic helical N,N'-linked oligoureas are one such class of AMP mimics with activities in vitro against a broad range of bacteria including Bacillus anthracis, a Gram-positive sporulating bacillus and causing agent of anthrax. 28687228 2 47 theme N 278:278 arg1 oligoureas 290:299 Amphiphilic cationic helical N,N'-linked oligoureas 249:299 oligoureas 290:299 Amphiphilic cationic helical N,N'-linked oligoureas are one such class of AMP mimics with activities in vitro against a broad range of bacteria including Bacillus anthracis, a Gram-positive sporulating bacillus and causing agent of anthrax. 28687228 5 48 theme urea→guanidinium 965:980 arg1 replacements 982:993 Urea→thiourea and urea→guanidinium replacements 947:993 replacements 982:993 Urea→thiourea and urea→guanidinium replacements close to the negative end of the helix dipole led to analogues with increased potency and selectivity for B. anthracis versus mammalian cells. 28687228 4 49 theme germinated 902:911 arg1 spores 913:918 germinated spores 902:918 germinated spores 902:918 A series of analogues in which urea linkages at selected positions are replaced by thiourea and guanidium surrogates have been prepared on solid support and tested against different bacterial forms of B. anthracis (germinated spores and encapsulated bacilli). 28687228 0 50 theme surrogates 67:76 arg1 Effect 0:5 Effect 0:5 Effect of replacing main-chain ureas with thiourea and guanidinium surrogates on the bactericidal activity of membrane active oligourea 0:134 Effect of replacing main-chain ureas with thiourea and guanidinium surrogates on the bactericidal activity of membrane active oligourea foldamers. 28687228 2 51 theme helical 270:276 arg1 class 314:318 one such class 305:318 one such class of AMP mimics with activities in vitro against a broad range of bacteria including Bacillus anthracis, a Gram-positive sporulating bacillus and causing agent of anthrax 305:487 Amphiphilic cationic helical N,N'-linked oligoureas are one such class of AMP mimics with activities in vitro against a broad range of bacteria including Bacillus anthracis, a Gram-positive sporulating bacillus and causing agent of anthrax. 28687228 2 51 theme helical 270:276 arg1 oligoureas 290:299 Amphiphilic cationic helical N,N'-linked oligoureas 249:299 oligoureas 290:299 Amphiphilic cationic helical N,N'-linked oligoureas are one such class of AMP mimics with activities in vitro against a broad range of bacteria including Bacillus anthracis, a Gram-positive sporulating bacillus and causing agent of anthrax. 28687228 2 52 theme broad 369:373 arg1 range 375:379 a broad range 367:379 a broad range of bacteria including Bacillus anthracis, a Gram-positive sporulating bacillus and causing agent of anthrax 367:487 Amphiphilic cationic helical N,N'-linked oligoureas are one such class of AMP mimics with activities in vitro against a broad range of bacteria including Bacillus anthracis, a Gram-positive sporulating bacillus and causing agent of anthrax. 28687228 0 53 theme guanidinium 55:65 arg1 surrogates 67:76 guanidinium surrogates 55:76 guanidinium surrogates 55:76 Effect of replacing main-chain ureas with thiourea and guanidinium surrogates on the bactericidal activity of membrane active oligourea foldamers. 28687228 2 54 theme cationic 261:268 arg1 class 314:318 one such class 305:318 one such class of AMP mimics with activities in vitro against a broad range of bacteria including Bacillus anthracis, a Gram-positive sporulating bacillus and causing agent of anthrax 305:487 Amphiphilic cationic helical N,N'-linked oligoureas are one such class of AMP mimics with activities in vitro against a broad range of bacteria including Bacillus anthracis, a Gram-positive sporulating bacillus and causing agent of anthrax. 28687228 2 54 theme cationic 261:268 arg1 oligoureas 290:299 Amphiphilic cationic helical N,N'-linked oligoureas 249:299 oligoureas 290:299 Amphiphilic cationic helical N,N'-linked oligoureas are one such class of AMP mimics with activities in vitro against a broad range of bacteria including Bacillus anthracis, a Gram-positive sporulating bacillus and causing agent of anthrax. 27561202 7 0 theme in vivo 1140:1146 arg1 bioactivities 1148:1160 the in vivo bioactivities 1136:1160 the in vivo bioactivities of FSH glycoforms in Fshb null mice 1136:1196 Here, we evaluated the in vivo bioactivities of FSH glycoforms in Fshb null mice using a pharmacological rescue approach. 27561202 10 1 theme signaling 1652:1660 arg1 components 1662:1671 key signaling components 1648:1671 key signaling components downstream of the FSH-receptor 1648:1702 Western blot analyses followed by densitometry of key signaling components downstream of the FSH-receptor confirmed that the hypo-glycosylated FSH21/18 elicited a response similar to that by fully-glycosylated FSH24 in ovaries of Fshb null mice. 27561202 1 2 theme N-linked 217:224 arg1 glycans 226:232 N-linked glycans 217:232 N-linked glycans at Asn7 and Asn24 residues that are co-translationally attached early during subunit biosynthesis 217:330 The hormone - specific FSHβ subunit of the human FSH heterodimer consists of N-linked glycans at Asn7 and Asn24 residues that are co-translationally attached early during subunit biosynthesis. 27561202 7 3 from bioactivities 1148:1160 arg1 mice 1193:1196 Fshb null mice 1183:1196 Fshb null mice 1183:1196 Here, we evaluated the in vivo bioactivities of FSH glycoforms in Fshb null mice using a pharmacological rescue approach. 27561202 6 4 theme glycoform 1084:1092 arg1 bioactivity 1043:1053 the in vivo bioactivity 1031:1053 the in vivo bioactivity of the hypo-glycosylated FSH glycoform 1031:1092 However, the in vivo bioactivity of the hypo-glycosylated FSH glycoform has never been tested. 27561202 1 5 from residues 252:259 arg1 glycans 226:232 N-linked glycans 217:232 N-linked glycans at Asn7 and Asn24 residues that are co-translationally attached early during subunit biosynthesis 217:330 The hormone - specific FSHβ subunit of the human FSH heterodimer consists of N-linked glycans at Asn7 and Asn24 residues that are co-translationally attached early during subunit biosynthesis. 27561202 3 6 theme FSH 488:490 arg1 glycoforms 492:501 The resulting FSH glycoforms 474:501 The resulting FSH glycoforms 474:501 The resulting FSH glycoforms are termed hypo-glycosylated (FSH21/18, missing either an Asn24 or Asn7 N-glycan chain on the β - subunit, respectively) or fully glycosylated (FSH24, possessing of both Asn7 and Asn24 N-linked glycans on the β - subunit) FSH. 27561202 4 7 theme FSH 764:766 arg1 FSH24 793:797 FSH24 793:797 FSH24 793:797 The recombinant versions of human FSH glycoforms (FSH21/18 and FSH24) have been purified and biochemically characterized. 27561202 4 7 theme FSH 764:766 arg1 FSH21/18 780:787 FSH21/18 780:787 FSH21/18 780:787 The recombinant versions of human FSH glycoforms (FSH21/18 and FSH24) have been purified and biochemically characterized. 27561202 4 7 theme FSH 764:766 arg1 glycoforms 768:777 human FSH glycoforms 758:777 human FSH glycoforms (FSH21/18 and FSH24) 758:798 The recombinant versions of human FSH glycoforms (FSH21/18 and FSH24) have been purified and biochemically characterized. 27561202 6 8 theme hypo-glycosylated 1062:1078 arg1 glycoform 1084:1092 the hypo-glycosylated FSH glycoform 1058:1092 the hypo-glycosylated FSH glycoform 1058:1092 However, the in vivo bioactivity of the hypo-glycosylated FSH glycoform has never been tested. 27561202 6 9 gly hypo-glycosylated 1062:1078 arg1 glycoform 1084:1092 the hypo-glycosylated FSH glycoform 1058:1092 the hypo-glycosylated FSH glycoform 1058:1092 However, the in vivo bioactivity of the hypo-glycosylated FSH glycoform has never been tested. 27561202 3 10 theme Asn7 673:676 arg1 glycans 697:703 both Asn7 and Asn24 N-linked glycans 668:703 both Asn7 and Asn24 N-linked glycans on the β 668:712 The resulting FSH glycoforms are termed hypo-glycosylated (FSH21/18, missing either an Asn24 or Asn7 N-glycan chain on the β - subunit, respectively) or fully glycosylated (FSH24, possessing of both Asn7 and Asn24 N-linked glycans on the β - subunit) FSH. 27561202 1 11 theme specific 154:161 arg1 subunit 168:174 The hormone - specific FSHβ subunit 140:174 subunit 168:174 The hormone - specific FSHβ subunit of the human FSH heterodimer consists of N-linked glycans at Asn7 and Asn24 residues that are co-translationally attached early during subunit biosynthesis. 27561202 12 12 theme FSH21/18 2088:2095 arg1 glycoform 2097:2105 recombinant hypo-glycosylated human FSH21/18 glycoform 2052:2105 recombinant hypo-glycosylated human FSH21/18 glycoform 2052:2105 Thus, our data establish that recombinant hypo-glycosylated human FSH21/18 glycoform elicits bioactivity in vivo similar to the fully-glycosylated FSH. 27561202 3 13 from possessing 654:663 arg1 β 712:712 the β 708:712 the β 708:712 The resulting FSH glycoforms are termed hypo-glycosylated (FSH21/18, missing either an Asn24 or Asn7 N-glycan chain on the β - subunit, respectively) or fully glycosylated (FSH24, possessing of both Asn7 and Asn24 N-linked glycans on the β - subunit) FSH. 27561202 0 14 theme human 100:104 arg1 glycoforms 110:119 human FSH glycoforms 100:119 human FSH glycoforms 100:119 Evaluation of in vivo bioactivities of recombinant hypo- (FSH21/18) and fully- (FSH24) glycosylated human FSH glycoforms in Fshb null mice. 27561202 3 15 theme hypo-glycosylated 514:530 arg1 FSH 725:727 hypo-glycosylated (FSH21/18, missing either an Asn24 or Asn7 N-glycan chain on the β - subunit, respectively) or fully glycosylated (FSH24, possessing of both Asn7 and Asn24 N-linked glycans on the β - subunit) FSH 514:727 hypo-glycosylated (FSH21/18, missing either an Asn24 or Asn7 N-glycan chain on the β - subunit, respectively) or fully glycosylated (FSH24, possessing of both Asn7 and Asn24 N-linked glycans on the β - subunit) FSH 514:727 The resulting FSH glycoforms are termed hypo-glycosylated (FSH21/18, missing either an Asn24 or Asn7 N-glycan chain on the β - subunit, respectively) or fully glycosylated (FSH24, possessing of both Asn7 and Asn24 N-linked glycans on the β - subunit) FSH. 27561202 13 16 theme glycoforms 2335:2344 arg1 combination 2300:2310 a combination 2298:2310 a combination of different human FSH glycoforms 2298:2344 Our studies may have clinical implications particularly in formulating FSH-based ovarian follicle induction protocols using a combination of different human FSH glycoforms. 27561202 12 17 gly fully-glycosylated 2150:2167 arg1 FSH 2169:2171 the fully-glycosylated FSH 2146:2171 the fully-glycosylated FSH 2146:2171 Thus, our data establish that recombinant hypo-glycosylated human FSH21/18 glycoform elicits bioactivity in vivo similar to the fully-glycosylated FSH. 27561202 10 18 theme similar 1770:1776 arg1 response 1761:1768 a response 1759:1768 a response similar to that by fully-glycosylated FSH24 in ovaries of Fshb null mice 1759:1841 Western blot analyses followed by densitometry of key signaling components downstream of the FSH-receptor confirmed that the hypo-glycosylated FSH21/18 elicited a response similar to that by fully-glycosylated FSH24 in ovaries of Fshb null mice. 27561202 13 19 theme follicle 2263:2270 arg1 protocols 2282:2290 FSH-based ovarian follicle induction protocols 2245:2290 FSH-based ovarian follicle induction protocols using a combination of different human FSH glycoforms 2245:2344 Our studies may have clinical implications particularly in formulating FSH-based ovarian follicle induction protocols using a combination of different human FSH glycoforms. 27561202 6 20 gly glycoform 1084:1092 arg1 FSH 1080:1082 the hypo-glycosylated FSH glycoform 1058:1092 the hypo-glycosylated FSH glycoform 1058:1092 However, the in vivo bioactivity of the hypo-glycosylated FSH glycoform has never been tested. 27561202 3 21 theme Asn24 N-linked 682:695 arg1 glycans 697:703 both Asn7 and Asn24 N-linked glycans 668:703 both Asn7 and Asn24 N-linked glycans on the β 668:712 The resulting FSH glycoforms are termed hypo-glycosylated (FSH21/18, missing either an Asn24 or Asn7 N-glycan chain on the β - subunit, respectively) or fully glycosylated (FSH24, possessing of both Asn7 and Asn24 N-linked glycans on the β - subunit) FSH. 27561202 0 22 theme Fshb 124:127 arg1 mice 134:137 Fshb null mice 124:137 Fshb null mice 124:137 Evaluation of in vivo bioactivities of recombinant hypo- (FSH21/18) and fully- (FSH24) glycosylated human FSH glycoforms in Fshb null mice. 27561202 8 23 theme ovarian 1364:1370 arg1 genes 1372:1376 ovarian genes 1364:1376 ovarian genes 1364:1376 In Fshb null female mice, both hypo- and fully-glycosylated FSH elicited an ovarian weight gain response by 48 h and induced ovarian genes in a dose- and time-dependent manner. 27561202 3 24 gly hypo-glycosylated 514:530 arg1 FSH 725:727 hypo-glycosylated (FSH21/18, missing either an Asn24 or Asn7 N-glycan chain on the β - subunit, respectively) or fully glycosylated (FSH24, possessing of both Asn7 and Asn24 N-linked glycans on the β - subunit) FSH 514:727 hypo-glycosylated (FSH21/18, missing either an Asn24 or Asn7 N-glycan chain on the β - subunit, respectively) or fully glycosylated (FSH24, possessing of both Asn7 and Asn24 N-linked glycans on the β - subunit) FSH 514:727 The resulting FSH glycoforms are termed hypo-glycosylated (FSH21/18, missing either an Asn24 or Asn7 N-glycan chain on the β - subunit, respectively) or fully glycosylated (FSH24, possessing of both Asn7 and Asn24 N-linked glycans on the β - subunit) FSH. 27561202 12 25 gly glycoform 2097:2105 arg1 FSH21/18 2088:2095 recombinant hypo-glycosylated human FSH21/18 glycoform 2052:2105 recombinant hypo-glycosylated human FSH21/18 glycoform 2052:2105 Thus, our data establish that recombinant hypo-glycosylated human FSH21/18 glycoform elicits bioactivity in vivo similar to the fully-glycosylated FSH. 27561202 3 26 theme N-glycan 575:582 arg1 chain 584:588 either an Asn24 or Asn7 N-glycan chain 551:588 chain 584:588 The resulting FSH glycoforms are termed hypo-glycosylated (FSH21/18, missing either an Asn24 or Asn7 N-glycan chain on the β - subunit, respectively) or fully glycosylated (FSH24, possessing of both Asn7 and Asn24 N-linked glycans on the β - subunit) FSH. 27561202 13 27 theme human 2325:2329 arg1 glycoforms 2335:2344 different human FSH glycoforms 2315:2344 different human FSH glycoforms 2315:2344 Our studies may have clinical implications particularly in formulating FSH-based ovarian follicle induction protocols using a combination of different human FSH glycoforms. 27561202 12 28 theme hypo-glycosylated 2064:2080 arg1 glycoform 2097:2105 recombinant hypo-glycosylated human FSH21/18 glycoform 2052:2105 recombinant hypo-glycosylated human FSH21/18 glycoform 2052:2105 Thus, our data establish that recombinant hypo-glycosylated human FSH21/18 glycoform elicits bioactivity in vivo similar to the fully-glycosylated FSH. 27561202 11 29 theme fully-glycosylated 1932:1949 arg1 FSH24 1951:1955 the fully-glycosylated FSH24 1928:1955 the fully-glycosylated FSH24 1928:1955 When injected into Fshb null males, hypo-glycosylated FSH21/18 was more active than the fully-glycosylated FSH24 in inducing FSH-responsive genes and Sertoli cell proliferation. 27561202 3 30 dep hypo-glycosylated 514:530 arg1 subunit 716:722 subunit 716:722 subunit 716:722 The resulting FSH glycoforms are termed hypo-glycosylated (FSH21/18, missing either an Asn24 or Asn7 N-glycan chain on the β - subunit, respectively) or fully glycosylated (FSH24, possessing of both Asn7 and Asn24 N-linked glycans on the β - subunit) FSH. 27561202 3 30 dep hypo-glycosylated 514:530 arg1 FSH24 647:651 FSH24 647:651 FSH24 647:651 The resulting FSH glycoforms are termed hypo-glycosylated (FSH21/18, missing either an Asn24 or Asn7 N-glycan chain on the β - subunit, respectively) or fully glycosylated (FSH24, possessing of both Asn7 and Asn24 N-linked glycans on the β - subunit) FSH. 27561202 3 30 dep hypo-glycosylated 514:530 arg1 FSH21/18 533:540 FSH21/18 533:540 FSH21/18 533:540 The resulting FSH glycoforms are termed hypo-glycosylated (FSH21/18, missing either an Asn24 or Asn7 N-glycan chain on the β - subunit, respectively) or fully glycosylated (FSH24, possessing of both Asn7 and Asn24 N-linked glycans on the β - subunit) FSH. 27561202 3 30 dep hypo-glycosylated 514:530 arg1 possessing 654:663 possessing 654:663 possessing of both Asn7 and Asn24 N-linked glycans on the β 654:712 The resulting FSH glycoforms are termed hypo-glycosylated (FSH21/18, missing either an Asn24 or Asn7 N-glycan chain on the β - subunit, respectively) or fully glycosylated (FSH24, possessing of both Asn7 and Asn24 N-linked glycans on the β - subunit) FSH. 27561202 8 31 theme dose- 1383:1387 arg1 manner 1408:1413 a dose- and time-dependent manner 1381:1413 a dose- and time-dependent manner 1381:1413 In Fshb null female mice, both hypo- and fully-glycosylated FSH elicited an ovarian weight gain response by 48 h and induced ovarian genes in a dose- and time-dependent manner. 27561202 1 32 theme subunit 311:317 arg1 biosynthesis 319:330 subunit biosynthesis 311:330 subunit biosynthesis 311:330 The hormone - specific FSHβ subunit of the human FSH heterodimer consists of N-linked glycans at Asn7 and Asn24 residues that are co-translationally attached early during subunit biosynthesis. 27561202 3 33 dep FSH21/18 533:540 arg1 subunit 601:607 subunit 601:607 subunit 601:607 The resulting FSH glycoforms are termed hypo-glycosylated (FSH21/18, missing either an Asn24 or Asn7 N-glycan chain on the β - subunit, respectively) or fully glycosylated (FSH24, possessing of both Asn7 and Asn24 N-linked glycans on the β - subunit) FSH. 27561202 8 34 theme time-dependent 1393:1406 arg1 manner 1408:1413 a dose- and time-dependent manner 1381:1413 a dose- and time-dependent manner 1381:1413 In Fshb null female mice, both hypo- and fully-glycosylated FSH elicited an ovarian weight gain response by 48 h and induced ovarian genes in a dose- and time-dependent manner. 27561202 8 35 theme null 1247:1250 arg1 mice 1259:1262 Fshb null female mice 1242:1262 Fshb null female mice 1242:1262 In Fshb null female mice, both hypo- and fully-glycosylated FSH elicited an ovarian weight gain response by 48 h and induced ovarian genes in a dose- and time-dependent manner. 27561202 5 36 from assay 1000:1004 arg1 active 973:978 active 973:978 active 973:978 In vitro functional studies have indicated that FSH21/18 exhibits faster FSH- receptor binding kinetics and is much more active than FSH24 in every assay tested to date. 27561202 9 37 theme qPCR 1444:1447 arg1 assays 1449:1454 real time qPCR assays 1434:1454 real time qPCR assays 1434:1454 Quantification by real time qPCR assays indicated that hypo-glycosylated FSH21/18 was bioactive in vivo and induced FSH-responsive ovarian genes similar to fully-glycosylated FSH24. 27561202 11 38 theme Fshb 1863:1866 arg1 males 1873:1877 Fshb null males 1863:1877 Fshb null males 1863:1877 When injected into Fshb null males, hypo-glycosylated FSH21/18 was more active than the fully-glycosylated FSH24 in inducing FSH-responsive genes and Sertoli cell proliferation. 27561202 2 39 from subunit 409:415 arg1 number 352:357 the number 348:357 the number of N-glycans (none, one or two) on the human FSHβ subunit 348:415 Differences in the number of N-glycans (none, one or two) on the human FSHβ subunit contribute to macroheterogeneity in the FSH heterodimer. 27561202 1 40 theme Asn7 237:240 arg1 residues 252:259 Asn7 and Asn24 residues 237:259 Asn7 and Asn24 residues that are co-translationally attached early during subunit biosynthesis 237:330 The hormone - specific FSHβ subunit of the human FSH heterodimer consists of N-linked glycans at Asn7 and Asn24 residues that are co-translationally attached early during subunit biosynthesis. 27561202 5 41 theme In vitro 852:859 arg1 studies 872:878 In vitro functional studies 852:878 In vitro functional studies 852:878 In vitro functional studies have indicated that FSH21/18 exhibits faster FSH- receptor binding kinetics and is much more active than FSH24 in every assay tested to date. 27561202 13 42 theme ovarian 2255:2261 arg1 protocols 2282:2290 FSH-based ovarian follicle induction protocols 2245:2290 FSH-based ovarian follicle induction protocols using a combination of different human FSH glycoforms 2245:2344 Our studies may have clinical implications particularly in formulating FSH-based ovarian follicle induction protocols using a combination of different human FSH glycoforms. 27561202 9 43 theme bioactive 1502:1510 arg1 in vivo 1512:1518 bioactive in vivo 1502:1518 bioactive in vivo 1502:1518 Quantification by real time qPCR assays indicated that hypo-glycosylated FSH21/18 was bioactive in vivo and induced FSH-responsive ovarian genes similar to fully-glycosylated FSH24. 27561202 11 44 theme hypo-glycosylated 1880:1896 arg1 FSH21/18 1898:1905 hypo-glycosylated FSH21/18 1880:1905 hypo-glycosylated FSH21/18 1880:1905 When injected into Fshb null males, hypo-glycosylated FSH21/18 was more active than the fully-glycosylated FSH24 in inducing FSH-responsive genes and Sertoli cell proliferation. 27561202 0 45 theme in vivo 14:20 arg1 bioactivities 22:34 in vivo bioactivities 14:34 in vivo bioactivities of recombinant hypo- (FSH21/18) and fully- (FSH24) 14:85 Evaluation of in vivo bioactivities of recombinant hypo- (FSH21/18) and fully- (FSH24) glycosylated human FSH glycoforms in Fshb null mice. 27561202 1 46 theme Asn24 246:250 arg1 residues 252:259 Asn7 and Asn24 residues 237:259 Asn7 and Asn24 residues that are co-translationally attached early during subunit biosynthesis 237:330 The hormone - specific FSHβ subunit of the human FSH heterodimer consists of N-linked glycans at Asn7 and Asn24 residues that are co-translationally attached early during subunit biosynthesis. 27561202 10 47 theme FSH-receptor 1691:1702 arg1 downstream 1673:1682 downstream 1673:1682 downstream 1673:1682 Western blot analyses followed by densitometry of key signaling components downstream of the FSH-receptor confirmed that the hypo-glycosylated FSH21/18 elicited a response similar to that by fully-glycosylated FSH24 in ovaries of Fshb null mice. 27561202 10 48 from FSH24 1808:1812 arg1 ovaries 1817:1823 ovaries 1817:1823 ovaries of Fshb null mice 1817:1841 Western blot analyses followed by densitometry of key signaling components downstream of the FSH-receptor confirmed that the hypo-glycosylated FSH21/18 elicited a response similar to that by fully-glycosylated FSH24 in ovaries of Fshb null mice. 27561202 7 49 theme pharmacological 1206:1220 arg1 approach 1229:1236 a pharmacological rescue approach 1204:1236 a pharmacological rescue approach 1204:1236 Here, we evaluated the in vivo bioactivities of FSH glycoforms in Fshb null mice using a pharmacological rescue approach. 27561202 10 50 theme blot 1606:1609 arg1 analyses 1611:1618 Western blot analyses 1598:1618 Western blot analyses followed by densitometry of key signaling components downstream of the FSH-receptor 1598:1702 Western blot analyses followed by densitometry of key signaling components downstream of the FSH-receptor confirmed that the hypo-glycosylated FSH21/18 elicited a response similar to that by fully-glycosylated FSH24 in ovaries of Fshb null mice. 27561202 13 51 theme clinical 2195:2202 arg1 implications 2204:2215 clinical implications 2195:2215 clinical implications 2195:2215 Our studies may have clinical implications particularly in formulating FSH-based ovarian follicle induction protocols using a combination of different human FSH glycoforms. 27561202 13 52 contain have 2190:2193 arg1 studies 2178:2184 Our studies 2174:2184 Our studies 2174:2184 Our studies may have clinical implications particularly in formulating FSH-based ovarian follicle induction protocols using a combination of different human FSH glycoforms. 27561202 13 52 contain have 2190:2193 arg2 implications 2204:2215 clinical implications 2195:2215 clinical implications 2195:2215 Our studies may have clinical implications particularly in formulating FSH-based ovarian follicle induction protocols using a combination of different human FSH glycoforms. 27561202 2 53 theme FSHβ 404:407 arg1 subunit 409:415 the human FSHβ subunit 394:415 the human FSHβ subunit 394:415 Differences in the number of N-glycans (none, one or two) on the human FSHβ subunit contribute to macroheterogeneity in the FSH heterodimer. 27561202 9 54 gly hypo-glycosylated 1471:1487 arg1 FSH21/18 1489:1496 hypo-glycosylated FSH21/18 1471:1496 hypo-glycosylated FSH21/18 1471:1496 Quantification by real time qPCR assays indicated that hypo-glycosylated FSH21/18 was bioactive in vivo and induced FSH-responsive ovarian genes similar to fully-glycosylated FSH24. 27561202 3 55 from β 712:712 arg1 possessing 654:663 possessing 654:663 possessing of both Asn7 and Asn24 N-linked glycans on the β 654:712 The resulting FSH glycoforms are termed hypo-glycosylated (FSH21/18, missing either an Asn24 or Asn7 N-glycan chain on the β - subunit, respectively) or fully glycosylated (FSH24, possessing of both Asn7 and Asn24 N-linked glycans on the β - subunit) FSH. 27561202 4 56 theme recombinant 734:744 arg1 versions 746:753 The recombinant versions 730:753 The recombinant versions of human FSH glycoforms (FSH21/18 and FSH24) 730:798 The recombinant versions of human FSH glycoforms (FSH21/18 and FSH24) have been purified and biochemically characterized. 27561202 10 57 theme key 1648:1650 arg1 components 1662:1671 key signaling components 1648:1671 key signaling components downstream of the FSH-receptor 1648:1702 Western blot analyses followed by densitometry of key signaling components downstream of the FSH-receptor confirmed that the hypo-glycosylated FSH21/18 elicited a response similar to that by fully-glycosylated FSH24 in ovaries of Fshb null mice. 27561202 4 58 dep glycoforms 768:777 arg1 FSH24 793:797 FSH24 793:797 FSH24 793:797 The recombinant versions of human FSH glycoforms (FSH21/18 and FSH24) have been purified and biochemically characterized. 27561202 4 58 dep glycoforms 768:777 arg1 FSH21/18 780:787 FSH21/18 780:787 FSH21/18 780:787 The recombinant versions of human FSH glycoforms (FSH21/18 and FSH24) have been purified and biochemically characterized. 27561202 4 58 dep glycoforms 768:777 arg1 glycoforms 768:777 human FSH glycoforms 758:777 human FSH glycoforms (FSH21/18 and FSH24) 758:798 The recombinant versions of human FSH glycoforms (FSH21/18 and FSH24) have been purified and biochemically characterized. 27561202 7 59 theme null 1188:1191 arg1 mice 1193:1196 Fshb null mice 1183:1196 Fshb null mice 1183:1196 Here, we evaluated the in vivo bioactivities of FSH glycoforms in Fshb null mice using a pharmacological rescue approach. 27561202 8 60 theme weight 1323:1328 arg1 response 1335:1342 an ovarian weight gain response 1312:1342 an ovarian weight gain response 1312:1342 In Fshb null female mice, both hypo- and fully-glycosylated FSH elicited an ovarian weight gain response by 48 h and induced ovarian genes in a dose- and time-dependent manner. 27561202 9 61 theme similar 1561:1567 arg1 genes 1555:1559 FSH-responsive ovarian genes 1532:1559 FSH-responsive ovarian genes similar to fully-glycosylated FSH24 1532:1595 Quantification by real time qPCR assays indicated that hypo-glycosylated FSH21/18 was bioactive in vivo and induced FSH-responsive ovarian genes similar to fully-glycosylated FSH24. 27561202 8 62 gly fully-glycosylated 1280:1297 arg1 FSH 1299:1301 fully-glycosylated FSH 1280:1301 fully-glycosylated FSH 1280:1301 In Fshb null female mice, both hypo- and fully-glycosylated FSH elicited an ovarian weight gain response by 48 h and induced ovarian genes in a dose- and time-dependent manner. 27561202 7 63 gly glycoforms 1169:1178 arg1 FSH 1165:1167 FSH glycoforms 1165:1178 FSH glycoforms 1165:1178 Here, we evaluated the in vivo bioactivities of FSH glycoforms in Fshb null mice using a pharmacological rescue approach. 27561202 5 64 theme faster 918:923 arg1 kinetics 947:954 faster FSH- receptor binding kinetics 918:954 faster FSH- receptor binding kinetics 918:954 In vitro functional studies have indicated that FSH21/18 exhibits faster FSH- receptor binding kinetics and is much more active than FSH24 in every assay tested to date. 27561202 3 65 gly glycoforms 492:501 arg1 FSH 488:490 The resulting FSH glycoforms 474:501 The resulting FSH glycoforms 474:501 The resulting FSH glycoforms are termed hypo-glycosylated (FSH21/18, missing either an Asn24 or Asn7 N-glycan chain on the β - subunit, respectively) or fully glycosylated (FSH24, possessing of both Asn7 and Asn24 N-linked glycans on the β - subunit) FSH. 27561202 10 66 theme null 1833:1836 arg1 mice 1838:1841 Fshb null mice 1828:1841 Fshb null mice 1828:1841 Western blot analyses followed by densitometry of key signaling components downstream of the FSH-receptor confirmed that the hypo-glycosylated FSH21/18 elicited a response similar to that by fully-glycosylated FSH24 in ovaries of Fshb null mice. 27561202 1 67 theme heterodimer 193:203 arg1 hormone 144:150 The hormone - specific FSHβ subunit 140:174 hormone 144:150 The hormone - specific FSHβ subunit of the human FSH heterodimer consists of N-linked glycans at Asn7 and Asn24 residues that are co-translationally attached early during subunit biosynthesis. 27561202 5 68 theme receptor 930:937 arg1 kinetics 947:954 faster FSH- receptor binding kinetics 918:954 faster FSH- receptor binding kinetics 918:954 In vitro functional studies have indicated that FSH21/18 exhibits faster FSH- receptor binding kinetics and is much more active than FSH24 in every assay tested to date. 27561202 7 69 theme FSH 1165:1167 arg1 glycoforms 1169:1178 FSH glycoforms 1165:1178 FSH glycoforms 1165:1178 Here, we evaluated the in vivo bioactivities of FSH glycoforms in Fshb null mice using a pharmacological rescue approach. 27561202 10 70 theme fully-glycosylated 1789:1806 arg1 FSH24 1808:1812 fully-glycosylated FSH24 1789:1812 fully-glycosylated FSH24 in ovaries of Fshb null mice 1789:1841 Western blot analyses followed by densitometry of key signaling components downstream of the FSH-receptor confirmed that the hypo-glycosylated FSH21/18 elicited a response similar to that by fully-glycosylated FSH24 in ovaries of Fshb null mice. 27561202 3 71 theme glycosylated 633:644 arg1 FSH 725:727 hypo-glycosylated (FSH21/18, missing either an Asn24 or Asn7 N-glycan chain on the β - subunit, respectively) or fully glycosylated (FSH24, possessing of both Asn7 and Asn24 N-linked glycans on the β - subunit) FSH 514:727 hypo-glycosylated (FSH21/18, missing either an Asn24 or Asn7 N-glycan chain on the β - subunit, respectively) or fully glycosylated (FSH24, possessing of both Asn7 and Asn24 N-linked glycans on the β - subunit) FSH 514:727 The resulting FSH glycoforms are termed hypo-glycosylated (FSH21/18, missing either an Asn24 or Asn7 N-glycan chain on the β - subunit, respectively) or fully glycosylated (FSH24, possessing of both Asn7 and Asn24 N-linked glycans on the β - subunit) FSH. 27561202 10 72 theme components 1662:1671 arg1 densitometry 1632:1643 densitometry 1632:1643 densitometry of key signaling components downstream of the FSH-receptor 1632:1702 Western blot analyses followed by densitometry of key signaling components downstream of the FSH-receptor confirmed that the hypo-glycosylated FSH21/18 elicited a response similar to that by fully-glycosylated FSH24 in ovaries of Fshb null mice. 27561202 11 73 gly hypo-glycosylated 1880:1896 arg1 FSH21/18 1898:1905 hypo-glycosylated FSH21/18 1880:1905 hypo-glycosylated FSH21/18 1880:1905 When injected into Fshb null males, hypo-glycosylated FSH21/18 was more active than the fully-glycosylated FSH24 in inducing FSH-responsive genes and Sertoli cell proliferation. 27561202 4 74 theme glycoforms 768:777 arg1 versions 746:753 The recombinant versions 730:753 The recombinant versions of human FSH glycoforms (FSH21/18 and FSH24) 730:798 The recombinant versions of human FSH glycoforms (FSH21/18 and FSH24) have been purified and biochemically characterized. 27561202 6 75 theme in vivo 1035:1041 arg1 bioactivity 1043:1053 the in vivo bioactivity 1031:1053 the in vivo bioactivity of the hypo-glycosylated FSH glycoform 1031:1092 However, the in vivo bioactivity of the hypo-glycosylated FSH glycoform has never been tested. 27561202 1 76 link N-linked 217:224 arg1 glycans 226:232 N-linked glycans 217:232 N-linked glycans at Asn7 and Asn24 residues that are co-translationally attached early during subunit biosynthesis 217:330 The hormone - specific FSHβ subunit of the human FSH heterodimer consists of N-linked glycans at Asn7 and Asn24 residues that are co-translationally attached early during subunit biosynthesis. 27561202 3 77 theme resulting 478:486 arg1 glycoforms 492:501 The resulting FSH glycoforms 474:501 The resulting FSH glycoforms 474:501 The resulting FSH glycoforms are termed hypo-glycosylated (FSH21/18, missing either an Asn24 or Asn7 N-glycan chain on the β - subunit, respectively) or fully glycosylated (FSH24, possessing of both Asn7 and Asn24 N-linked glycans on the β - subunit) FSH. 27561202 4 78 gly glycoforms 768:777 arg1 FSH 764:766 human FSH glycoforms 758:777 human FSH glycoforms (FSH21/18 and FSH24) 758:798 The recombinant versions of human FSH glycoforms (FSH21/18 and FSH24) have been purified and biochemically characterized. 27561202 0 79 theme hypo- 51:55 arg1 bioactivities 22:34 in vivo bioactivities 14:34 in vivo bioactivities of recombinant hypo- (FSH21/18) and fully- (FSH24) 14:85 Evaluation of in vivo bioactivities of recombinant hypo- (FSH21/18) and fully- (FSH24) glycosylated human FSH glycoforms in Fshb null mice. 27561202 2 80 from Differences 333:343 arg1 number 352:357 the number 348:357 the number of N-glycans (none, one or two) on the human FSHβ subunit 348:415 Differences in the number of N-glycans (none, one or two) on the human FSHβ subunit contribute to macroheterogeneity in the FSH heterodimer. 27561202 6 81 theme FSH 1080:1082 arg1 glycoform 1084:1092 the hypo-glycosylated FSH glycoform 1058:1092 the hypo-glycosylated FSH glycoform 1058:1092 However, the in vivo bioactivity of the hypo-glycosylated FSH glycoform has never been tested. 27561202 13 82 theme different 2315:2323 arg1 glycoforms 2335:2344 different human FSH glycoforms 2315:2344 different human FSH glycoforms 2315:2344 Our studies may have clinical implications particularly in formulating FSH-based ovarian follicle induction protocols using a combination of different human FSH glycoforms. 27561202 4 83 theme human 758:762 arg1 FSH24 793:797 FSH24 793:797 FSH24 793:797 The recombinant versions of human FSH glycoforms (FSH21/18 and FSH24) have been purified and biochemically characterized. 27561202 4 83 theme human 758:762 arg1 FSH21/18 780:787 FSH21/18 780:787 FSH21/18 780:787 The recombinant versions of human FSH glycoforms (FSH21/18 and FSH24) have been purified and biochemically characterized. 27561202 4 83 theme human 758:762 arg1 glycoforms 768:777 human FSH glycoforms 758:777 human FSH glycoforms (FSH21/18 and FSH24) 758:798 The recombinant versions of human FSH glycoforms (FSH21/18 and FSH24) have been purified and biochemically characterized. 27561202 12 84 theme similar 2135:2141 arg1 in vivo 2127:2133 bioactivity in vivo 2115:2133 bioactivity in vivo similar to the fully-glycosylated FSH 2115:2171 Thus, our data establish that recombinant hypo-glycosylated human FSH21/18 glycoform elicits bioactivity in vivo similar to the fully-glycosylated FSH. 27561202 0 85 theme FSH 106:108 arg1 glycoforms 110:119 human FSH glycoforms 100:119 human FSH glycoforms 100:119 Evaluation of in vivo bioactivities of recombinant hypo- (FSH21/18) and fully- (FSH24) glycosylated human FSH glycoforms in Fshb null mice. 27561202 10 86 theme hypo-glycosylated 1723:1739 arg1 FSH21/18 1741:1748 the hypo-glycosylated FSH21/18 1719:1748 the hypo-glycosylated FSH21/18 1719:1748 Western blot analyses followed by densitometry of key signaling components downstream of the FSH-receptor confirmed that the hypo-glycosylated FSH21/18 elicited a response similar to that by fully-glycosylated FSH24 in ovaries of Fshb null mice. 27561202 1 87 theme FSHβ 163:166 arg1 subunit 168:174 The hormone - specific FSHβ subunit 140:174 subunit 168:174 The hormone - specific FSHβ subunit of the human FSH heterodimer consists of N-linked glycans at Asn7 and Asn24 residues that are co-translationally attached early during subunit biosynthesis. 27561202 2 88 from macroheterogeneity 431:448 arg1 heterodimer 461:471 the FSH heterodimer 453:471 the FSH heterodimer 453:471 Differences in the number of N-glycans (none, one or two) on the human FSHβ subunit contribute to macroheterogeneity in the FSH heterodimer. 27561202 9 89 theme hypo-glycosylated 1471:1487 arg1 FSH21/18 1489:1496 hypo-glycosylated FSH21/18 1471:1496 hypo-glycosylated FSH21/18 1471:1496 Quantification by real time qPCR assays indicated that hypo-glycosylated FSH21/18 was bioactive in vivo and induced FSH-responsive ovarian genes similar to fully-glycosylated FSH24. 27561202 9 90 theme real 1434:1437 arg1 assays 1449:1454 real time qPCR assays 1434:1454 real time qPCR assays 1434:1454 Quantification by real time qPCR assays indicated that hypo-glycosylated FSH21/18 was bioactive in vivo and induced FSH-responsive ovarian genes similar to fully-glycosylated FSH24. 27561202 12 91 theme human 2082:2086 arg1 glycoform 2097:2105 recombinant hypo-glycosylated human FSH21/18 glycoform 2052:2105 recombinant hypo-glycosylated human FSH21/18 glycoform 2052:2105 Thus, our data establish that recombinant hypo-glycosylated human FSH21/18 glycoform elicits bioactivity in vivo similar to the fully-glycosylated FSH. 27561202 3 92 link Asn24 N-linked 682:695 arg1 glycans 697:703 both Asn7 and Asn24 N-linked glycans 668:703 both Asn7 and Asn24 N-linked glycans on the β 668:712 The resulting FSH glycoforms are termed hypo-glycosylated (FSH21/18, missing either an Asn24 or Asn7 N-glycan chain on the β - subunit, respectively) or fully glycosylated (FSH24, possessing of both Asn7 and Asn24 N-linked glycans on the β - subunit) FSH. 27561202 0 93 theme null 129:132 arg1 mice 134:137 Fshb null mice 124:137 Fshb null mice 124:137 Evaluation of in vivo bioactivities of recombinant hypo- (FSH21/18) and fully- (FSH24) glycosylated human FSH glycoforms in Fshb null mice. 27561202 10 94 gly fully-glycosylated 1789:1806 arg1 FSH24 1808:1812 fully-glycosylated FSH24 1789:1812 fully-glycosylated FSH24 in ovaries of Fshb null mice 1789:1841 Western blot analyses followed by densitometry of key signaling components downstream of the FSH-receptor confirmed that the hypo-glycosylated FSH21/18 elicited a response similar to that by fully-glycosylated FSH24 in ovaries of Fshb null mice. 27561202 12 95 gly hypo-glycosylated 2064:2080 arg1 glycoform 2097:2105 recombinant hypo-glycosylated human FSH21/18 glycoform 2052:2105 recombinant hypo-glycosylated human FSH21/18 glycoform 2052:2105 Thus, our data establish that recombinant hypo-glycosylated human FSH21/18 glycoform elicits bioactivity in vivo similar to the fully-glycosylated FSH. 27561202 13 96 gly glycoforms 2335:2344 arg1 FSH 2331:2333 different human FSH glycoforms 2315:2344 different human FSH glycoforms 2315:2344 Our studies may have clinical implications particularly in formulating FSH-based ovarian follicle induction protocols using a combination of different human FSH glycoforms. 27561202 3 97 theme glycans 697:703 arg1 possessing 654:663 possessing 654:663 possessing of both Asn7 and Asn24 N-linked glycans on the β 654:712 The resulting FSH glycoforms are termed hypo-glycosylated (FSH21/18, missing either an Asn24 or Asn7 N-glycan chain on the β - subunit, respectively) or fully glycosylated (FSH24, possessing of both Asn7 and Asn24 N-linked glycans on the β - subunit) FSH. 27561202 12 98 theme fully-glycosylated 2150:2167 arg1 FSH 2169:2171 the fully-glycosylated FSH 2146:2171 the fully-glycosylated FSH 2146:2171 Thus, our data establish that recombinant hypo-glycosylated human FSH21/18 glycoform elicits bioactivity in vivo similar to the fully-glycosylated FSH. 27561202 3 99 theme Asn7 570:573 arg1 chain 584:588 either an Asn24 or Asn7 N-glycan chain 551:588 chain 584:588 The resulting FSH glycoforms are termed hypo-glycosylated (FSH21/18, missing either an Asn24 or Asn7 N-glycan chain on the β - subunit, respectively) or fully glycosylated (FSH24, possessing of both Asn7 and Asn24 N-linked glycans on the β - subunit) FSH. 27561202 0 100 gly glycoforms 110:119 arg1 FSH 106:108 human FSH glycoforms 100:119 human FSH glycoforms 100:119 Evaluation of in vivo bioactivities of recombinant hypo- (FSH21/18) and fully- (FSH24) glycosylated human FSH glycoforms in Fshb null mice. 27561202 11 101 theme Sertoli 1994:2000 arg1 proliferation 2007:2019 Sertoli cell proliferation 1994:2019 Sertoli cell proliferation 1994:2019 When injected into Fshb null males, hypo-glycosylated FSH21/18 was more active than the fully-glycosylated FSH24 in inducing FSH-responsive genes and Sertoli cell proliferation. 27561202 12 102 theme recombinant 2052:2062 arg1 glycoform 2097:2105 recombinant hypo-glycosylated human FSH21/18 glycoform 2052:2105 recombinant hypo-glycosylated human FSH21/18 glycoform 2052:2105 Thus, our data establish that recombinant hypo-glycosylated human FSH21/18 glycoform elicits bioactivity in vivo similar to the fully-glycosylated FSH. 27561202 5 103 from active 973:978 arg1 assay 1000:1004 every assay 994:1004 every assay tested to date 994:1019 In vitro functional studies have indicated that FSH21/18 exhibits faster FSH- receptor binding kinetics and is much more active than FSH24 in every assay tested to date. 27561202 13 104 theme FSH 2331:2333 arg1 glycoforms 2335:2344 different human FSH glycoforms 2315:2344 different human FSH glycoforms 2315:2344 Our studies may have clinical implications particularly in formulating FSH-based ovarian follicle induction protocols using a combination of different human FSH glycoforms. 27561202 13 105 theme induction 2272:2280 arg1 protocols 2282:2290 FSH-based ovarian follicle induction protocols 2245:2290 FSH-based ovarian follicle induction protocols using a combination of different human FSH glycoforms 2245:2344 Our studies may have clinical implications particularly in formulating FSH-based ovarian follicle induction protocols using a combination of different human FSH glycoforms. 27561202 1 106 theme human 183:187 arg1 heterodimer 193:203 the human FSH heterodimer 179:203 the human FSH heterodimer 179:203 The hormone - specific FSHβ subunit of the human FSH heterodimer consists of N-linked glycans at Asn7 and Asn24 residues that are co-translationally attached early during subunit biosynthesis. 27561202 0 107 theme fully- 72:77 arg1 bioactivities 22:34 in vivo bioactivities 14:34 in vivo bioactivities of recombinant hypo- (FSH21/18) and fully- (FSH24) 14:85 Evaluation of in vivo bioactivities of recombinant hypo- (FSH21/18) and fully- (FSH24) glycosylated human FSH glycoforms in Fshb null mice. 27561202 3 108 from glycans 697:703 arg1 β 712:712 the β 708:712 the β 708:712 The resulting FSH glycoforms are termed hypo-glycosylated (FSH21/18, missing either an Asn24 or Asn7 N-glycan chain on the β - subunit, respectively) or fully glycosylated (FSH24, possessing of both Asn7 and Asn24 N-linked glycans on the β - subunit) FSH. 27561202 9 109 theme ovarian 1547:1553 arg1 genes 1555:1559 FSH-responsive ovarian genes 1532:1559 FSH-responsive ovarian genes similar to fully-glycosylated FSH24 1532:1595 Quantification by real time qPCR assays indicated that hypo-glycosylated FSH21/18 was bioactive in vivo and induced FSH-responsive ovarian genes similar to fully-glycosylated FSH24. 27561202 9 110 theme time 1439:1442 arg1 assays 1449:1454 real time qPCR assays 1434:1454 real time qPCR assays 1434:1454 Quantification by real time qPCR assays indicated that hypo-glycosylated FSH21/18 was bioactive in vivo and induced FSH-responsive ovarian genes similar to fully-glycosylated FSH24. 27561202 11 111 theme cell 2002:2005 arg1 proliferation 2007:2019 Sertoli cell proliferation 1994:2019 Sertoli cell proliferation 1994:2019 When injected into Fshb null males, hypo-glycosylated FSH21/18 was more active than the fully-glycosylated FSH24 in inducing FSH-responsive genes and Sertoli cell proliferation. 27561202 8 112 theme Fshb 1242:1245 arg1 mice 1259:1262 Fshb null female mice 1242:1262 Fshb null female mice 1242:1262 In Fshb null female mice, both hypo- and fully-glycosylated FSH elicited an ovarian weight gain response by 48 h and induced ovarian genes in a dose- and time-dependent manner. 27561202 2 113 theme FSH 457:459 arg1 heterodimer 461:471 the FSH heterodimer 453:471 the FSH heterodimer 453:471 Differences in the number of N-glycans (none, one or two) on the human FSHβ subunit contribute to macroheterogeneity in the FSH heterodimer. 27561202 8 114 theme female 1252:1257 arg1 mice 1259:1262 Fshb null female mice 1242:1262 Fshb null female mice 1242:1262 In Fshb null female mice, both hypo- and fully-glycosylated FSH elicited an ovarian weight gain response by 48 h and induced ovarian genes in a dose- and time-dependent manner. 27561202 2 115 theme N-glycans 362:370 arg1 number 352:357 the number 348:357 the number of N-glycans (none, one or two) on the human FSHβ subunit 348:415 Differences in the number of N-glycans (none, one or two) on the human FSHβ subunit contribute to macroheterogeneity in the FSH heterodimer. 27561202 9 116 theme fully-glycosylated 1572:1589 arg1 FSH24 1591:1595 fully-glycosylated FSH24 1572:1595 fully-glycosylated FSH24 1572:1595 Quantification by real time qPCR assays indicated that hypo-glycosylated FSH21/18 was bioactive in vivo and induced FSH-responsive ovarian genes similar to fully-glycosylated FSH24. 27561202 7 117 theme rescue 1222:1227 arg1 approach 1229:1236 a pharmacological rescue approach 1204:1236 a pharmacological rescue approach 1204:1236 Here, we evaluated the in vivo bioactivities of FSH glycoforms in Fshb null mice using a pharmacological rescue approach. 27561202 0 118 theme bioactivities 22:34 arg1 Evaluation 0:9 Evaluation 0:9 Evaluation of in vivo bioactivities of recombinant hypo- (FSH21/18) and fully- (FSH24) 0:85 Evaluation of in vivo bioactivities of recombinant hypo- (FSH21/18) and fully- (FSH24) glycosylated human FSH glycoforms in Fshb null mice. 27561202 13 119 theme FSH-based 2245:2253 arg1 protocols 2282:2290 FSH-based ovarian follicle induction protocols 2245:2290 FSH-based ovarian follicle induction protocols using a combination of different human FSH glycoforms 2245:2344 Our studies may have clinical implications particularly in formulating FSH-based ovarian follicle induction protocols using a combination of different human FSH glycoforms. 27561202 5 120 theme functional 861:870 arg1 studies 872:878 In vitro functional studies 852:878 In vitro functional studies 852:878 In vitro functional studies have indicated that FSH21/18 exhibits faster FSH- receptor binding kinetics and is much more active than FSH24 in every assay tested to date. 27561202 11 121 gly fully-glycosylated 1932:1949 arg1 FSH24 1951:1955 the fully-glycosylated FSH24 1928:1955 the fully-glycosylated FSH24 1928:1955 When injected into Fshb null males, hypo-glycosylated FSH21/18 was more active than the fully-glycosylated FSH24 in inducing FSH-responsive genes and Sertoli cell proliferation. 27561202 10 122 theme Fshb 1828:1831 arg1 mice 1838:1841 Fshb null mice 1828:1841 Fshb null mice 1828:1841 Western blot analyses followed by densitometry of key signaling components downstream of the FSH-receptor confirmed that the hypo-glycosylated FSH21/18 elicited a response similar to that by fully-glycosylated FSH24 in ovaries of Fshb null mice. 27561202 10 123 gly hypo-glycosylated 1723:1739 arg1 FSH21/18 1741:1748 the hypo-glycosylated FSH21/18 1719:1748 the hypo-glycosylated FSH21/18 1719:1748 Western blot analyses followed by densitometry of key signaling components downstream of the FSH-receptor confirmed that the hypo-glycosylated FSH21/18 elicited a response similar to that by fully-glycosylated FSH24 in ovaries of Fshb null mice. 27561202 5 124 theme binding 939:945 arg1 kinetics 947:954 faster FSH- receptor binding kinetics 918:954 faster FSH- receptor binding kinetics 918:954 In vitro functional studies have indicated that FSH21/18 exhibits faster FSH- receptor binding kinetics and is much more active than FSH24 in every assay tested to date. 27561202 3 125 gly glycosylated 633:644 arg1 FSH 725:727 hypo-glycosylated (FSH21/18, missing either an Asn24 or Asn7 N-glycan chain on the β - subunit, respectively) or fully glycosylated (FSH24, possessing of both Asn7 and Asn24 N-linked glycans on the β - subunit) FSH 514:727 hypo-glycosylated (FSH21/18, missing either an Asn24 or Asn7 N-glycan chain on the β - subunit, respectively) or fully glycosylated (FSH24, possessing of both Asn7 and Asn24 N-linked glycans on the β - subunit) FSH 514:727 The resulting FSH glycoforms are termed hypo-glycosylated (FSH21/18, missing either an Asn24 or Asn7 N-glycan chain on the β - subunit, respectively) or fully glycosylated (FSH24, possessing of both Asn7 and Asn24 N-linked glycans on the β - subunit) FSH. 27561202 8 126 theme fully-glycosylated 1280:1297 arg1 FSH 1299:1301 fully-glycosylated FSH 1280:1301 fully-glycosylated FSH 1280:1301 In Fshb null female mice, both hypo- and fully-glycosylated FSH elicited an ovarian weight gain response by 48 h and induced ovarian genes in a dose- and time-dependent manner. 27561202 10 127 theme Western 1598:1604 arg1 analyses 1611:1618 Western blot analyses 1598:1618 Western blot analyses followed by densitometry of key signaling components downstream of the FSH-receptor 1598:1702 Western blot analyses followed by densitometry of key signaling components downstream of the FSH-receptor confirmed that the hypo-glycosylated FSH21/18 elicited a response similar to that by fully-glycosylated FSH24 in ovaries of Fshb null mice. 27561202 2 128 from number 352:357 arg1 subunit 409:415 the human FSHβ subunit 394:415 the human FSHβ subunit 394:415 Differences in the number of N-glycans (none, one or two) on the human FSHβ subunit contribute to macroheterogeneity in the FSH heterodimer. 27561202 7 129 theme Fshb 1183:1186 arg1 mice 1193:1196 Fshb null mice 1183:1196 Fshb null mice 1183:1196 Here, we evaluated the in vivo bioactivities of FSH glycoforms in Fshb null mice using a pharmacological rescue approach. 27561202 2 130 theme human 398:402 arg1 subunit 409:415 the human FSHβ subunit 394:415 the human FSHβ subunit 394:415 Differences in the number of N-glycans (none, one or two) on the human FSHβ subunit contribute to macroheterogeneity in the FSH heterodimer. 27561202 9 131 gly fully-glycosylated 1572:1589 arg1 FSH24 1591:1595 fully-glycosylated FSH24 1572:1595 fully-glycosylated FSH24 1572:1595 Quantification by real time qPCR assays indicated that hypo-glycosylated FSH21/18 was bioactive in vivo and induced FSH-responsive ovarian genes similar to fully-glycosylated FSH24. 27561202 2 132 dep N-glycans 362:370 arg1 two 386:388 two 386:388 two 386:388 Differences in the number of N-glycans (none, one or two) on the human FSHβ subunit contribute to macroheterogeneity in the FSH heterodimer. 27561202 2 132 dep N-glycans 362:370 arg1 one 379:381 one 379:381 one 379:381 Differences in the number of N-glycans (none, one or two) on the human FSHβ subunit contribute to macroheterogeneity in the FSH heterodimer. 27561202 2 132 dep N-glycans 362:370 arg1 none 373:376 none 373:376 none 373:376 Differences in the number of N-glycans (none, one or two) on the human FSHβ subunit contribute to macroheterogeneity in the FSH heterodimer. 27561202 9 133 theme FSH-responsive 1532:1545 arg1 genes 1555:1559 FSH-responsive ovarian genes 1532:1559 FSH-responsive ovarian genes similar to fully-glycosylated FSH24 1532:1595 Quantification by real time qPCR assays indicated that hypo-glycosylated FSH21/18 was bioactive in vivo and induced FSH-responsive ovarian genes similar to fully-glycosylated FSH24. 27561202 2 134 from N-glycans 362:370 arg1 subunit 409:415 the human FSHβ subunit 394:415 the human FSHβ subunit 394:415 Differences in the number of N-glycans (none, one or two) on the human FSHβ subunit contribute to macroheterogeneity in the FSH heterodimer. 27561202 7 135 theme glycoforms 1169:1178 arg1 bioactivities 1148:1160 the in vivo bioactivities 1136:1160 the in vivo bioactivities of FSH glycoforms in Fshb null mice 1136:1196 Here, we evaluated the in vivo bioactivities of FSH glycoforms in Fshb null mice using a pharmacological rescue approach. 27561202 11 136 theme FSH-responsive 1969:1982 arg1 genes 1984:1988 FSH-responsive genes 1969:1988 FSH-responsive genes 1969:1988 When injected into Fshb null males, hypo-glycosylated FSH21/18 was more active than the fully-glycosylated FSH24 in inducing FSH-responsive genes and Sertoli cell proliferation. 27561202 10 137 theme mice 1838:1841 arg1 ovaries 1817:1823 ovaries 1817:1823 ovaries of Fshb null mice 1817:1841 Western blot analyses followed by densitometry of key signaling components downstream of the FSH-receptor confirmed that the hypo-glycosylated FSH21/18 elicited a response similar to that by fully-glycosylated FSH24 in ovaries of Fshb null mice. 27561202 8 138 theme ovarian 1315:1321 arg1 response 1335:1342 an ovarian weight gain response 1312:1342 an ovarian weight gain response 1312:1342 In Fshb null female mice, both hypo- and fully-glycosylated FSH elicited an ovarian weight gain response by 48 h and induced ovarian genes in a dose- and time-dependent manner. 27561202 1 139 theme FSH 189:191 arg1 heterodimer 193:203 the human FSH heterodimer 179:203 the human FSH heterodimer 179:203 The hormone - specific FSHβ subunit of the human FSH heterodimer consists of N-linked glycans at Asn7 and Asn24 residues that are co-translationally attached early during subunit biosynthesis. 27561202 5 140 theme FSH- 925:928 arg1 kinetics 947:954 faster FSH- receptor binding kinetics 918:954 faster FSH- receptor binding kinetics 918:954 In vitro functional studies have indicated that FSH21/18 exhibits faster FSH- receptor binding kinetics and is much more active than FSH24 in every assay tested to date. 27561202 11 141 theme null 1868:1871 arg1 males 1873:1877 Fshb null males 1863:1877 Fshb null males 1863:1877 When injected into Fshb null males, hypo-glycosylated FSH21/18 was more active than the fully-glycosylated FSH24 in inducing FSH-responsive genes and Sertoli cell proliferation. 27561202 8 142 theme gain 1330:1333 arg1 response 1335:1342 an ovarian weight gain response 1312:1342 an ovarian weight gain response 1312:1342 In Fshb null female mice, both hypo- and fully-glycosylated FSH elicited an ovarian weight gain response by 48 h and induced ovarian genes in a dose- and time-dependent manner. 27561202 10 143 theme downstream 1673:1682 arg1 components 1662:1671 key signaling components 1648:1671 key signaling components downstream of the FSH-receptor 1648:1702 Western blot analyses followed by densitometry of key signaling components downstream of the FSH-receptor confirmed that the hypo-glycosylated FSH21/18 elicited a response similar to that by fully-glycosylated FSH24 in ovaries of Fshb null mice. 24994778 10 0 theme phylogenetic 1201:1212 arg1 analysis 1214:1221 phylogenetic analysis 1201:1221 phylogenetic analysis 1201:1221 Based on the phylogenetic analysis and physiological properties of the novel isolate we propose a novel species of the genus Thermosipho, Thermosipho activus sp. 24994778 9 1 theme gene 998:1001 arg1 sequences 1003:1011 16S rRNA gene sequences 989:1011 16S rRNA gene sequences 989:1011 Phylogenetic analysis of 16S rRNA gene sequences showed the affiliation of strain Rift-s3(T) with the genus Thermosipho, with Thermosipho atlanticus Ob7(T) as the closest relative (96.5 % 16S rRNA gene sequence similarity). 24994778 9 2 theme strain 1039:1044 arg1 T 1054:1054 T 1054:1054 T 1054:1054 Phylogenetic analysis of 16S rRNA gene sequences showed the affiliation of strain Rift-s3(T) with the genus Thermosipho, with Thermosipho atlanticus Ob7(T) as the closest relative (96.5 % 16S rRNA gene sequence similarity). 24994778 9 2 theme strain 1039:1044 arg1 Rift-s3 1046:1052 strain Rift-s3 1039:1052 strain Rift-s3(T) 1039:1055 Phylogenetic analysis of 16S rRNA gene sequences showed the affiliation of strain Rift-s3(T) with the genus Thermosipho, with Thermosipho atlanticus Ob7(T) as the closest relative (96.5 % 16S rRNA gene sequence similarity). 24994778 9 3 theme sequences 1003:1011 arg1 analysis 977:984 Phylogenetic analysis 964:984 Phylogenetic analysis of 16S rRNA gene sequences 964:1011 Phylogenetic analysis of 16S rRNA gene sequences showed the affiliation of strain Rift-s3(T) with the genus Thermosipho, with Thermosipho atlanticus Ob7(T) as the closest relative (96.5 % 16S rRNA gene sequence similarity). 24994778 7 4 theme carbon 861:866 arg1 hydrogen 848:855 hydrogen 848:855 hydrogen 848:855 Acetate, hydrogen and carbon dioxide were the main products of glucose fermentation. 24994778 7 4 theme carbon 861:866 arg1 dioxide 868:874 carbon dioxide 861:874 carbon dioxide 861:874 Acetate, hydrogen and carbon dioxide were the main products of glucose fermentation. 24994778 7 4 theme carbon 861:866 arg1 Acetate 839:845 Acetate 839:845 Acetate 839:845 Acetate, hydrogen and carbon dioxide were the main products of glucose fermentation. 24994778 7 4 theme carbon 861:866 arg1 products 890:897 the main products 881:897 the main products of glucose fermentation 881:921 Acetate, hydrogen and carbon dioxide were the main products of glucose fermentation. 24994778 2 5 theme California 309:318 arg1 Gulf 301:304 Gulf 301:304 Gulf of California 301:318 A novel obligately anaerobic, extremely thermophilic, organotrophic bacterium, strain Rift-s3(T), was isolated from a deep-sea sample containing Riftia pachyptila sheath from Guaymas Basin, Gulf of California. 24994778 2 5 theme California 309:318 arg1 Basin 294:298 Guaymas Basin 286:298 Guaymas Basin 286:298 A novel obligately anaerobic, extremely thermophilic, organotrophic bacterium, strain Rift-s3(T), was isolated from a deep-sea sample containing Riftia pachyptila sheath from Guaymas Basin, Gulf of California. 24994778 9 6 theme rRNA 1156:1159 arg1 relative 1135:1142 the closest relative 1123:1142 the closest relative (96.5 % 16S rRNA gene sequence similarity) 1123:1185 Phylogenetic analysis of 16S rRNA gene sequences showed the affiliation of strain Rift-s3(T) with the genus Thermosipho, with Thermosipho atlanticus Ob7(T) as the closest relative (96.5 % 16S rRNA gene sequence similarity). 24994778 9 6 theme rRNA 1156:1159 arg1 similarity 1175:1184 96.5 % 16S rRNA gene sequence similarity 1145:1184 96.5 % 16S rRNA gene sequence similarity 1145:1184 Phylogenetic analysis of 16S rRNA gene sequences showed the affiliation of strain Rift-s3(T) with the genus Thermosipho, with Thermosipho atlanticus Ob7(T) as the closest relative (96.5 % 16S rRNA gene sequence similarity). 24994778 3 7 from µm 367:368 arg1 length 396:401 length 396:401 length 396:401 Cells of the novel isolate were rods, 0.3-0.8 µm in width and 1.5-10 µm in length, surrounded by a sheath-like structure (toga). 24994778 3 7 from µm 367:368 arg1 width 373:377 width 373:377 width 373:377 Cells of the novel isolate were rods, 0.3-0.8 µm in width and 1.5-10 µm in length, surrounded by a sheath-like structure (toga). 24994778 9 8 with Thermosipho 1072:1082 arg1 T 1117:1117 T 1117:1117 T 1117:1117 Phylogenetic analysis of 16S rRNA gene sequences showed the affiliation of strain Rift-s3(T) with the genus Thermosipho, with Thermosipho atlanticus Ob7(T) as the closest relative (96.5 % 16S rRNA gene sequence similarity). 24994778 9 8 with Thermosipho 1072:1082 arg1 Ob7 1113:1115 Thermosipho atlanticus Ob7 1090:1115 Thermosipho atlanticus Ob7(T) 1090:1118 Phylogenetic analysis of 16S rRNA gene sequences showed the affiliation of strain Rift-s3(T) with the genus Thermosipho, with Thermosipho atlanticus Ob7(T) as the closest relative (96.5 % 16S rRNA gene sequence similarity). 24994778 2 9 theme Riftia 256:261 arg1 pachyptila 263:272 Riftia pachyptila 256:272 Riftia pachyptila sheath 256:279 A novel obligately anaerobic, extremely thermophilic, organotrophic bacterium, strain Rift-s3(T), was isolated from a deep-sea sample containing Riftia pachyptila sheath from Guaymas Basin, Gulf of California. 24994778 4 10 theme g 573:573 arg1 l 575:575 3 to 60 g l(-1) 565:579 3 to 60 g l(-1) 565:579 Strain Rift-s3(T) grew at temperatures ranging from 44 to 75 °C, at pH 5.5 to 8.0, and with NaCl concentrations of 3 to 60 g l(-1). 24994778 2 11 theme anaerobic 130:138 arg1 bacterium 179:187 A novel obligately anaerobic, extremely thermophilic, organotrophic bacterium 111:187 A novel obligately anaerobic, extremely thermophilic, organotrophic bacterium 111:187 A novel obligately anaerobic, extremely thermophilic, organotrophic bacterium, strain Rift-s3(T), was isolated from a deep-sea sample containing Riftia pachyptila sheath from Guaymas Basin, Gulf of California. 24994778 2 11 theme anaerobic 130:138 arg1 Rift-s3 197:203 strain Rift-s3 190:203 strain Rift-s3(T) 190:206 A novel obligately anaerobic, extremely thermophilic, organotrophic bacterium, strain Rift-s3(T), was isolated from a deep-sea sample containing Riftia pachyptila sheath from Guaymas Basin, Gulf of California. 24994778 9 12 theme 96.5  1145:1149 arg1 % 1150:1150 % 1150:1150 % 1150:1150 Phylogenetic analysis of 16S rRNA gene sequences showed the affiliation of strain Rift-s3(T) with the genus Thermosipho, with Thermosipho atlanticus Ob7(T) as the closest relative (96.5 % 16S rRNA gene sequence similarity). 24994778 8 13 theme G+C 928:930 arg1 % 961:961 30 mol% 955:961 30 mol% 955:961 The G+C content of the DNA was 30 mol%. 24994778 8 13 theme G+C 928:930 arg1 content 932:938 The G+C content 924:938 The G+C content of the DNA 924:949 The G+C content of the DNA was 30 mol%. 24994778 8 14 theme mol 958:960 arg1 % 961:961 30 mol% 955:961 30 mol% 955:961 The G+C content of the DNA was 30 mol%. 24994778 8 14 theme mol 958:960 arg1 content 932:938 The G+C content 924:938 The G+C content of the DNA 924:949 The G+C content of the DNA was 30 mol%. 24994778 10 15 theme physiological 1227:1239 arg1 properties 1241:1250 physiological properties 1227:1250 physiological properties 1227:1250 Based on the phylogenetic analysis and physiological properties of the novel isolate we propose a novel species of the genus Thermosipho, Thermosipho activus sp. 24994778 10 16 theme activus 1338:1344 arg1 species 1292:1298 a novel species 1284:1298 a novel species of the genus Thermosipho 1284:1323 Based on the phylogenetic analysis and physiological properties of the novel isolate we propose a novel species of the genus Thermosipho, Thermosipho activus sp. 24994778 10 16 theme activus 1338:1344 arg1 sp 1346:1347 Thermosipho activus sp 1326:1347 Thermosipho activus sp 1326:1347 Based on the phylogenetic analysis and physiological properties of the novel isolate we propose a novel species of the genus Thermosipho, Thermosipho activus sp. 24994778 2 17 theme deep-sea 229:236 arg1 sample 238:243 a deep-sea sample 227:243 a deep-sea sample containing Riftia pachyptila sheath from Guaymas Basin, Gulf of California 227:318 A novel obligately anaerobic, extremely thermophilic, organotrophic bacterium, strain Rift-s3(T), was isolated from a deep-sea sample containing Riftia pachyptila sheath from Guaymas Basin, Gulf of California. 24994778 10 18 theme Thermosipho 1313:1323 arg1 sp 1346:1347 Thermosipho activus sp 1326:1347 Thermosipho activus sp 1326:1347 Based on the phylogenetic analysis and physiological properties of the novel isolate we propose a novel species of the genus Thermosipho, Thermosipho activus sp. 24994778 10 18 theme Thermosipho 1313:1323 arg1 species 1292:1298 a novel species 1284:1298 a novel species of the genus Thermosipho 1284:1323 Based on the phylogenetic analysis and physiological properties of the novel isolate we propose a novel species of the genus Thermosipho, Thermosipho activus sp. 24994778 0 19 theme activus 12:18 arg1 sp 20:21 Thermosipho activus sp 0:21 Thermosipho activus sp. 0:22 Thermosipho activus sp. 24994778 2 20 theme novel 113:117 arg1 bacterium 179:187 A novel obligately anaerobic, extremely thermophilic, organotrophic bacterium 111:187 A novel obligately anaerobic, extremely thermophilic, organotrophic bacterium 111:187 A novel obligately anaerobic, extremely thermophilic, organotrophic bacterium, strain Rift-s3(T), was isolated from a deep-sea sample containing Riftia pachyptila sheath from Guaymas Basin, Gulf of California. 24994778 2 20 theme novel 113:117 arg1 Rift-s3 197:203 strain Rift-s3 190:203 strain Rift-s3(T) 190:206 A novel obligately anaerobic, extremely thermophilic, organotrophic bacterium, strain Rift-s3(T), was isolated from a deep-sea sample containing Riftia pachyptila sheath from Guaymas Basin, Gulf of California. 24994778 2 21 theme Guaymas 286:292 arg1 Gulf 301:304 Gulf 301:304 Gulf of California 301:318 A novel obligately anaerobic, extremely thermophilic, organotrophic bacterium, strain Rift-s3(T), was isolated from a deep-sea sample containing Riftia pachyptila sheath from Guaymas Basin, Gulf of California. 24994778 2 21 theme Guaymas 286:292 arg1 Basin 294:298 Guaymas Basin 286:298 Guaymas Basin 286:298 A novel obligately anaerobic, extremely thermophilic, organotrophic bacterium, strain Rift-s3(T), was isolated from a deep-sea sample containing Riftia pachyptila sheath from Guaymas Basin, Gulf of California. 24994778 7 22 theme glucose 902:908 arg1 fermentation 910:921 glucose fermentation 902:921 glucose fermentation 902:921 Acetate, hydrogen and carbon dioxide were the main products of glucose fermentation. 24994778 9 23 theme gene 1161:1164 arg1 relative 1135:1142 the closest relative 1123:1142 the closest relative (96.5 % 16S rRNA gene sequence similarity) 1123:1185 Phylogenetic analysis of 16S rRNA gene sequences showed the affiliation of strain Rift-s3(T) with the genus Thermosipho, with Thermosipho atlanticus Ob7(T) as the closest relative (96.5 % 16S rRNA gene sequence similarity). 24994778 9 23 theme gene 1161:1164 arg1 similarity 1175:1184 96.5 % 16S rRNA gene sequence similarity 1145:1184 96.5 % 16S rRNA gene sequence similarity 1145:1184 Phylogenetic analysis of 16S rRNA gene sequences showed the affiliation of strain Rift-s3(T) with the genus Thermosipho, with Thermosipho atlanticus Ob7(T) as the closest relative (96.5 % 16S rRNA gene sequence similarity). 24994778 0 24 theme Thermosipho 0:10 arg1 sp 20:21 Thermosipho activus sp 0:21 Thermosipho activus sp. 0:22 Thermosipho activus sp. 24994778 9 25 theme Rift-s3 1046:1052 arg1 affiliation 1024:1034 the affiliation 1020:1034 the affiliation of strain Rift-s3(T) 1020:1055 Phylogenetic analysis of 16S rRNA gene sequences showed the affiliation of strain Rift-s3(T) with the genus Thermosipho, with Thermosipho atlanticus Ob7(T) as the closest relative (96.5 % 16S rRNA gene sequence similarity). 24994778 9 25 theme Rift-s3 1046:1052 arg1 relative 1135:1142 the closest relative 1123:1142 the closest relative (96.5 % 16S rRNA gene sequence similarity) 1123:1185 Phylogenetic analysis of 16S rRNA gene sequences showed the affiliation of strain Rift-s3(T) with the genus Thermosipho, with Thermosipho atlanticus Ob7(T) as the closest relative (96.5 % 16S rRNA gene sequence similarity). 24994778 9 26 theme atlanticus 1102:1111 arg1 T 1117:1117 T 1117:1117 T 1117:1117 Phylogenetic analysis of 16S rRNA gene sequences showed the affiliation of strain Rift-s3(T) with the genus Thermosipho, with Thermosipho atlanticus Ob7(T) as the closest relative (96.5 % 16S rRNA gene sequence similarity). 24994778 9 26 theme atlanticus 1102:1111 arg1 Ob7 1113:1115 Thermosipho atlanticus Ob7 1090:1115 Thermosipho atlanticus Ob7(T) 1090:1118 Phylogenetic analysis of 16S rRNA gene sequences showed the affiliation of strain Rift-s3(T) with the genus Thermosipho, with Thermosipho atlanticus Ob7(T) as the closest relative (96.5 % 16S rRNA gene sequence similarity). 24994778 5 27 theme NaCl 623:626 arg1 -1 635:636 -1 635:636 -1 635:636 Under optimum conditions (65 °C, pH 6.0, NaCl 25 g l(-1)), the doubling time was 30 min. 24994778 5 27 theme NaCl 623:626 arg1 l 633:633 NaCl 25 g l 623:633 NaCl 25 g l(-1) 623:637 Under optimum conditions (65 °C, pH 6.0, NaCl 25 g l(-1)), the doubling time was 30 min. 24994778 5 27 theme NaCl 623:626 arg1 °C 611:612 65 °C 608:612 65 °C 608:612 Under optimum conditions (65 °C, pH 6.0, NaCl 25 g l(-1)), the doubling time was 30 min. 24994778 5 28 dep conditions 596:605 arg1 pH 615:616 pH 6.0 615:620 pH 6.0 615:620 Under optimum conditions (65 °C, pH 6.0, NaCl 25 g l(-1)), the doubling time was 30 min. 24994778 5 28 dep conditions 596:605 arg1 °C 611:612 65 °C 608:612 65 °C 608:612 Under optimum conditions (65 °C, pH 6.0, NaCl 25 g l(-1)), the doubling time was 30 min. 24994778 5 28 dep conditions 596:605 arg1 l 633:633 NaCl 25 g l 623:633 NaCl 25 g l(-1) 623:637 Under optimum conditions (65 °C, pH 6.0, NaCl 25 g l(-1)), the doubling time was 30 min. 24994778 10 29 theme genus 1307:1311 arg1 Thermosipho 1313:1323 the genus Thermosipho 1303:1323 the genus Thermosipho 1303:1323 Based on the phylogenetic analysis and physiological properties of the novel isolate we propose a novel species of the genus Thermosipho, Thermosipho activus sp. 24994778 4 30 dep 60 570:571 arg1 to 567:568 to 567:568 to 567:568 Strain Rift-s3(T) grew at temperatures ranging from 44 to 75 °C, at pH 5.5 to 8.0, and with NaCl concentrations of 3 to 60 g l(-1). 24994778 9 31 theme closest 1127:1133 arg1 similarity 1175:1184 96.5 % 16S rRNA gene sequence similarity 1145:1184 96.5 % 16S rRNA gene sequence similarity 1145:1184 Phylogenetic analysis of 16S rRNA gene sequences showed the affiliation of strain Rift-s3(T) with the genus Thermosipho, with Thermosipho atlanticus Ob7(T) as the closest relative (96.5 % 16S rRNA gene sequence similarity). 24994778 9 31 theme closest 1127:1133 arg1 affiliation 1024:1034 the affiliation 1020:1034 the affiliation of strain Rift-s3(T) 1020:1055 Phylogenetic analysis of 16S rRNA gene sequences showed the affiliation of strain Rift-s3(T) with the genus Thermosipho, with Thermosipho atlanticus Ob7(T) as the closest relative (96.5 % 16S rRNA gene sequence similarity). 24994778 9 31 theme closest 1127:1133 arg1 relative 1135:1142 the closest relative 1123:1142 the closest relative (96.5 % 16S rRNA gene sequence similarity) 1123:1185 Phylogenetic analysis of 16S rRNA gene sequences showed the affiliation of strain Rift-s3(T) with the genus Thermosipho, with Thermosipho atlanticus Ob7(T) as the closest relative (96.5 % 16S rRNA gene sequence similarity). 24994778 5 32 theme g 631:631 arg1 -1 635:636 -1 635:636 -1 635:636 Under optimum conditions (65 °C, pH 6.0, NaCl 25 g l(-1)), the doubling time was 30 min. 24994778 5 32 theme g 631:631 arg1 l 633:633 NaCl 25 g l 623:633 NaCl 25 g l(-1) 623:637 Under optimum conditions (65 °C, pH 6.0, NaCl 25 g l(-1)), the doubling time was 30 min. 24994778 5 32 theme g 631:631 arg1 °C 611:612 65 °C 608:612 65 °C 608:612 Under optimum conditions (65 °C, pH 6.0, NaCl 25 g l(-1)), the doubling time was 30 min. 24994778 3 33 theme novel 334:338 arg1 isolate 340:346 the novel isolate 330:346 the novel isolate 330:346 Cells of the novel isolate were rods, 0.3-0.8 µm in width and 1.5-10 µm in length, surrounded by a sheath-like structure (toga). 24994778 2 34 contain containing 245:254 arg2 sheath 274:279 Riftia pachyptila sheath 256:279 Riftia pachyptila sheath 256:279 A novel obligately anaerobic, extremely thermophilic, organotrophic bacterium, strain Rift-s3(T), was isolated from a deep-sea sample containing Riftia pachyptila sheath from Guaymas Basin, Gulf of California. 24994778 2 34 contain containing 245:254 arg1 sample 238:243 a deep-sea sample 227:243 a deep-sea sample containing Riftia pachyptila sheath from Guaymas Basin, Gulf of California 227:318 A novel obligately anaerobic, extremely thermophilic, organotrophic bacterium, strain Rift-s3(T), was isolated from a deep-sea sample containing Riftia pachyptila sheath from Guaymas Basin, Gulf of California. 24994778 2 35 theme pachyptila 263:272 arg1 sheath 274:279 Riftia pachyptila sheath 256:279 Riftia pachyptila sheath 256:279 A novel obligately anaerobic, extremely thermophilic, organotrophic bacterium, strain Rift-s3(T), was isolated from a deep-sea sample containing Riftia pachyptila sheath from Guaymas Basin, Gulf of California. 24994778 1 36 dep thermophilic 32:43 arg1 hydrolytic 57:66 hydrolytic 57:66 hydrolytic 57:66 nov., a thermophilic, anaerobic, hydrolytic bacterium isolated from a deep-sea sample. 24994778 1 36 dep thermophilic 32:43 arg1 anaerobic 46:54 anaerobic 46:54 anaerobic 46:54 nov., a thermophilic, anaerobic, hydrolytic bacterium isolated from a deep-sea sample. 24994778 2 37 dep anaerobic 130:138 arg1 organotrophic 165:177 organotrophic 165:177 organotrophic 165:177 A novel obligately anaerobic, extremely thermophilic, organotrophic bacterium, strain Rift-s3(T), was isolated from a deep-sea sample containing Riftia pachyptila sheath from Guaymas Basin, Gulf of California. 24994778 2 37 dep anaerobic 130:138 arg1 thermophilic 151:162 thermophilic 151:162 thermophilic 151:162 A novel obligately anaerobic, extremely thermophilic, organotrophic bacterium, strain Rift-s3(T), was isolated from a deep-sea sample containing Riftia pachyptila sheath from Guaymas Basin, Gulf of California. 24994778 7 38 theme fermentation 910:921 arg1 hydrogen 848:855 hydrogen 848:855 hydrogen 848:855 Acetate, hydrogen and carbon dioxide were the main products of glucose fermentation. 24994778 7 38 theme fermentation 910:921 arg1 dioxide 868:874 carbon dioxide 861:874 carbon dioxide 861:874 Acetate, hydrogen and carbon dioxide were the main products of glucose fermentation. 24994778 7 38 theme fermentation 910:921 arg1 Acetate 839:845 Acetate 839:845 Acetate 839:845 Acetate, hydrogen and carbon dioxide were the main products of glucose fermentation. 24994778 7 38 theme fermentation 910:921 arg1 products 890:897 the main products 881:897 the main products of glucose fermentation 881:921 Acetate, hydrogen and carbon dioxide were the main products of glucose fermentation. 24994778 9 39 theme % 1150:1150 arg1 relative 1135:1142 the closest relative 1123:1142 the closest relative (96.5 % 16S rRNA gene sequence similarity) 1123:1185 Phylogenetic analysis of 16S rRNA gene sequences showed the affiliation of strain Rift-s3(T) with the genus Thermosipho, with Thermosipho atlanticus Ob7(T) as the closest relative (96.5 % 16S rRNA gene sequence similarity). 24994778 9 39 theme % 1150:1150 arg1 similarity 1175:1184 96.5 % 16S rRNA gene sequence similarity 1145:1184 96.5 % 16S rRNA gene sequence similarity 1145:1184 Phylogenetic analysis of 16S rRNA gene sequences showed the affiliation of strain Rift-s3(T) with the genus Thermosipho, with Thermosipho atlanticus Ob7(T) as the closest relative (96.5 % 16S rRNA gene sequence similarity). 24994778 7 40 theme main 885:888 arg1 hydrogen 848:855 hydrogen 848:855 hydrogen 848:855 Acetate, hydrogen and carbon dioxide were the main products of glucose fermentation. 24994778 7 40 theme main 885:888 arg1 dioxide 868:874 carbon dioxide 861:874 carbon dioxide 861:874 Acetate, hydrogen and carbon dioxide were the main products of glucose fermentation. 24994778 7 40 theme main 885:888 arg1 Acetate 839:845 Acetate 839:845 Acetate 839:845 Acetate, hydrogen and carbon dioxide were the main products of glucose fermentation. 24994778 7 40 theme main 885:888 arg1 products 890:897 the main products 881:897 the main products of glucose fermentation 881:921 Acetate, hydrogen and carbon dioxide were the main products of glucose fermentation. 24994778 4 41 theme Strain 450:455 arg1 Rift-s3 457:463 Strain Rift-s3 450:463 Strain Rift-s3(T) 450:466 Strain Rift-s3(T) grew at temperatures ranging from 44 to 75 °C, at pH 5.5 to 8.0, and with NaCl concentrations of 3 to 60 g l(-1). 24994778 4 41 theme Strain 450:455 arg1 T 465:465 T 465:465 T 465:465 Strain Rift-s3(T) grew at temperatures ranging from 44 to 75 °C, at pH 5.5 to 8.0, and with NaCl concentrations of 3 to 60 g l(-1). 24994778 10 42 theme isolate 1265:1271 arg1 analysis 1214:1221 phylogenetic analysis 1201:1221 phylogenetic analysis 1201:1221 Based on the phylogenetic analysis and physiological properties of the novel isolate we propose a novel species of the genus Thermosipho, Thermosipho activus sp. 24994778 10 42 theme isolate 1265:1271 arg1 properties 1241:1250 physiological properties 1227:1250 physiological properties 1227:1250 Based on the phylogenetic analysis and physiological properties of the novel isolate we propose a novel species of the genus Thermosipho, Thermosipho activus sp. 24994778 3 43 from µm 390:391 arg1 length 396:401 length 396:401 length 396:401 Cells of the novel isolate were rods, 0.3-0.8 µm in width and 1.5-10 µm in length, surrounded by a sheath-like structure (toga). 24994778 3 43 from µm 390:391 arg1 width 373:377 width 373:377 width 373:377 Cells of the novel isolate were rods, 0.3-0.8 µm in width and 1.5-10 µm in length, surrounded by a sheath-like structure (toga). 24994778 9 44 theme 16S 1152:1154 arg1 relative 1135:1142 the closest relative 1123:1142 the closest relative (96.5 % 16S rRNA gene sequence similarity) 1123:1185 Phylogenetic analysis of 16S rRNA gene sequences showed the affiliation of strain Rift-s3(T) with the genus Thermosipho, with Thermosipho atlanticus Ob7(T) as the closest relative (96.5 % 16S rRNA gene sequence similarity). 24994778 9 44 theme 16S 1152:1154 arg1 similarity 1175:1184 96.5 % 16S rRNA gene sequence similarity 1145:1184 96.5 % 16S rRNA gene sequence similarity 1145:1184 Phylogenetic analysis of 16S rRNA gene sequences showed the affiliation of strain Rift-s3(T) with the genus Thermosipho, with Thermosipho atlanticus Ob7(T) as the closest relative (96.5 % 16S rRNA gene sequence similarity). 24994778 10 45 theme novel 1286:1290 arg1 sp 1346:1347 Thermosipho activus sp 1326:1347 Thermosipho activus sp 1326:1347 Based on the phylogenetic analysis and physiological properties of the novel isolate we propose a novel species of the genus Thermosipho, Thermosipho activus sp. 24994778 10 45 theme novel 1286:1290 arg1 species 1292:1298 a novel species 1284:1298 a novel species of the genus Thermosipho 1284:1323 Based on the phylogenetic analysis and physiological properties of the novel isolate we propose a novel species of the genus Thermosipho, Thermosipho activus sp. 24994778 11 46 dep Rift-s3 1361:1367 arg1 B-2803 1395:1400  = DSM 26467(T) = VKM B-2803 1373:1400  = DSM 26467(T) = VKM B-2803(T) 1373:1403 nov., with Rift-s3(T) ( = DSM 26467(T) = VKM B-2803(T)) as the type strain. 24994778 11 46 dep Rift-s3 1361:1367 arg1 T 1402:1402 T 1402:1402 T 1402:1402 nov., with Rift-s3(T) ( = DSM 26467(T) = VKM B-2803(T)) as the type strain. 24994778 11 46 dep Rift-s3 1361:1367 arg1 strain 1418:1423 the type strain 1409:1423 the type strain 1409:1423 nov., with Rift-s3(T) ( = DSM 26467(T) = VKM B-2803(T)) as the type strain. 24994778 4 47 dep pH 518:519 arg1 to 525:526 to 525:526 to 525:526 Strain Rift-s3(T) grew at temperatures ranging from 44 to 75 °C, at pH 5.5 to 8.0, and with NaCl concentrations of 3 to 60 g l(-1). 24994778 1 48 theme deep-sea 94:101 arg1 sample 103:108 a deep-sea sample 92:108 a deep-sea sample 92:108 nov., a thermophilic, anaerobic, hydrolytic bacterium isolated from a deep-sea sample. 24994778 8 49 theme DNA 947:949 arg1 % 961:961 30 mol% 955:961 30 mol% 955:961 The G+C content of the DNA was 30 mol%. 24994778 8 49 theme DNA 947:949 arg1 content 932:938 The G+C content 924:938 The G+C content of the DNA 924:949 The G+C content of the DNA was 30 mol%. 24994778 9 50 theme genus 1066:1070 arg1 Thermosipho 1072:1082 the genus Thermosipho 1062:1082 the genus Thermosipho 1062:1082 Phylogenetic analysis of 16S rRNA gene sequences showed the affiliation of strain Rift-s3(T) with the genus Thermosipho, with Thermosipho atlanticus Ob7(T) as the closest relative (96.5 % 16S rRNA gene sequence similarity). 24994778 9 51 theme rRNA 993:996 arg1 sequences 1003:1011 16S rRNA gene sequences 989:1011 16S rRNA gene sequences 989:1011 Phylogenetic analysis of 16S rRNA gene sequences showed the affiliation of strain Rift-s3(T) with the genus Thermosipho, with Thermosipho atlanticus Ob7(T) as the closest relative (96.5 % 16S rRNA gene sequence similarity). 24994778 9 52 theme Phylogenetic 964:975 arg1 analysis 977:984 Phylogenetic analysis 964:984 Phylogenetic analysis of 16S rRNA gene sequences 964:1011 Phylogenetic analysis of 16S rRNA gene sequences showed the affiliation of strain Rift-s3(T) with the genus Thermosipho, with Thermosipho atlanticus Ob7(T) as the closest relative (96.5 % 16S rRNA gene sequence similarity). 24994778 3 53 theme sheath-like 420:430 arg1 toga 443:446 toga 443:446 toga 443:446 Cells of the novel isolate were rods, 0.3-0.8 µm in width and 1.5-10 µm in length, surrounded by a sheath-like structure (toga). 24994778 3 53 theme sheath-like 420:430 arg1 structure 432:440 a sheath-like structure 418:440 a sheath-like structure (toga) 418:447 Cells of the novel isolate were rods, 0.3-0.8 µm in width and 1.5-10 µm in length, surrounded by a sheath-like structure (toga). 24994778 11 54 theme type 1413:1416 arg1 strain 1418:1423 the type strain 1409:1423 the type strain 1409:1423 nov., with Rift-s3(T) ( = DSM 26467(T) = VKM B-2803(T)) as the type strain. 24994778 2 55 theme strain 190:195 arg1 T 205:205 T 205:205 T 205:205 A novel obligately anaerobic, extremely thermophilic, organotrophic bacterium, strain Rift-s3(T), was isolated from a deep-sea sample containing Riftia pachyptila sheath from Guaymas Basin, Gulf of California. 24994778 2 55 theme strain 190:195 arg1 bacterium 179:187 A novel obligately anaerobic, extremely thermophilic, organotrophic bacterium 111:187 A novel obligately anaerobic, extremely thermophilic, organotrophic bacterium 111:187 A novel obligately anaerobic, extremely thermophilic, organotrophic bacterium, strain Rift-s3(T), was isolated from a deep-sea sample containing Riftia pachyptila sheath from Guaymas Basin, Gulf of California. 24994778 2 55 theme strain 190:195 arg1 Rift-s3 197:203 strain Rift-s3 190:203 strain Rift-s3(T) 190:206 A novel obligately anaerobic, extremely thermophilic, organotrophic bacterium, strain Rift-s3(T), was isolated from a deep-sea sample containing Riftia pachyptila sheath from Guaymas Basin, Gulf of California. 24994778 4 56 theme l 575:575 arg1 concentrations 547:560 NaCl concentrations 542:560 NaCl concentrations of 3 to 60 g l(-1) 542:579 Strain Rift-s3(T) grew at temperatures ranging from 44 to 75 °C, at pH 5.5 to 8.0, and with NaCl concentrations of 3 to 60 g l(-1). 24994778 11 57 dep nov. 1350:1353 arg1 with 1356:1359 with 1356:1359 with 1356:1359 nov., with Rift-s3(T) ( = DSM 26467(T) = VKM B-2803(T)) as the type strain. 24994778 11 58 theme  = VKM 1388:1393 arg1 T 1402:1402 T 1402:1402 T 1402:1402 nov., with Rift-s3(T) ( = DSM 26467(T) = VKM B-2803(T)) as the type strain. 24994778 11 58 theme  = VKM 1388:1393 arg1 B-2803 1395:1400  = DSM 26467(T) = VKM B-2803 1373:1400  = DSM 26467(T) = VKM B-2803(T) 1373:1403 nov., with Rift-s3(T) ( = DSM 26467(T) = VKM B-2803(T)) as the type strain. 24994778 10 59 dep analysis 1214:1221 arg1 the 1197:1199 the 1197:1199 the 1197:1199 Based on the phylogenetic analysis and physiological properties of the novel isolate we propose a novel species of the genus Thermosipho, Thermosipho activus sp. 24994778 4 60 dep 75 508:509 arg1 to 505:506 to 505:506 to 505:506 Strain Rift-s3(T) grew at temperatures ranging from 44 to 75 °C, at pH 5.5 to 8.0, and with NaCl concentrations of 3 to 60 g l(-1). 24994778 10 61 theme Thermosipho 1326:1336 arg1 species 1292:1298 a novel species 1284:1298 a novel species of the genus Thermosipho 1284:1323 Based on the phylogenetic analysis and physiological properties of the novel isolate we propose a novel species of the genus Thermosipho, Thermosipho activus sp. 24994778 10 61 theme Thermosipho 1326:1336 arg1 sp 1346:1347 Thermosipho activus sp 1326:1347 Thermosipho activus sp 1326:1347 Based on the phylogenetic analysis and physiological properties of the novel isolate we propose a novel species of the genus Thermosipho, Thermosipho activus sp. 24994778 4 62 theme NaCl 542:545 arg1 concentrations 547:560 NaCl concentrations 542:560 NaCl concentrations of 3 to 60 g l(-1) 542:579 Strain Rift-s3(T) grew at temperatures ranging from 44 to 75 °C, at pH 5.5 to 8.0, and with NaCl concentrations of 3 to 60 g l(-1). 24994778 9 63 theme sequence 1166:1173 arg1 relative 1135:1142 the closest relative 1123:1142 the closest relative (96.5 % 16S rRNA gene sequence similarity) 1123:1185 Phylogenetic analysis of 16S rRNA gene sequences showed the affiliation of strain Rift-s3(T) with the genus Thermosipho, with Thermosipho atlanticus Ob7(T) as the closest relative (96.5 % 16S rRNA gene sequence similarity). 24994778 9 63 theme sequence 1166:1173 arg1 similarity 1175:1184 96.5 % 16S rRNA gene sequence similarity 1145:1184 96.5 % 16S rRNA gene sequence similarity 1145:1184 Phylogenetic analysis of 16S rRNA gene sequences showed the affiliation of strain Rift-s3(T) with the genus Thermosipho, with Thermosipho atlanticus Ob7(T) as the closest relative (96.5 % 16S rRNA gene sequence similarity). 24994778 9 64 theme 16S 989:991 arg1 sequences 1003:1011 16S rRNA gene sequences 989:1011 16S rRNA gene sequences 989:1011 Phylogenetic analysis of 16S rRNA gene sequences showed the affiliation of strain Rift-s3(T) with the genus Thermosipho, with Thermosipho atlanticus Ob7(T) as the closest relative (96.5 % 16S rRNA gene sequence similarity). 24994778 5 65 theme doubling 645:652 arg1 time 654:657 the doubling time 641:657 the doubling time 641:657 Under optimum conditions (65 °C, pH 6.0, NaCl 25 g l(-1)), the doubling time was 30 min. 24994778 5 65 theme doubling 645:652 arg1 min 666:668 30 min 663:668 30 min 663:668 Under optimum conditions (65 °C, pH 6.0, NaCl 25 g l(-1)), the doubling time was 30 min. 24994778 9 66 theme Thermosipho 1090:1100 arg1 T 1117:1117 T 1117:1117 T 1117:1117 Phylogenetic analysis of 16S rRNA gene sequences showed the affiliation of strain Rift-s3(T) with the genus Thermosipho, with Thermosipho atlanticus Ob7(T) as the closest relative (96.5 % 16S rRNA gene sequence similarity). 24994778 9 66 theme Thermosipho 1090:1100 arg1 Ob7 1113:1115 Thermosipho atlanticus Ob7 1090:1115 Thermosipho atlanticus Ob7(T) 1090:1118 Phylogenetic analysis of 16S rRNA gene sequences showed the affiliation of strain Rift-s3(T) with the genus Thermosipho, with Thermosipho atlanticus Ob7(T) as the closest relative (96.5 % 16S rRNA gene sequence similarity). 24994778 5 67 theme optimum 588:594 arg1 conditions 596:605 optimum conditions 588:605 optimum conditions (65 °C, pH 6.0, NaCl 25 g l(-1)) 588:638 Under optimum conditions (65 °C, pH 6.0, NaCl 25 g l(-1)), the doubling time was 30 min. 24994778 3 68 from rods 353:356 arg1 length 396:401 length 396:401 length 396:401 Cells of the novel isolate were rods, 0.3-0.8 µm in width and 1.5-10 µm in length, surrounded by a sheath-like structure (toga). 24994778 3 68 from rods 353:356 arg1 width 373:377 width 373:377 width 373:377 Cells of the novel isolate were rods, 0.3-0.8 µm in width and 1.5-10 µm in length, surrounded by a sheath-like structure (toga). 24994778 1 69 theme thermophilic 32:43 arg1 nov. 24:27 nov. 24:27 nov. 24:27 nov., a thermophilic, anaerobic, hydrolytic bacterium isolated from a deep-sea sample. 24994778 1 69 theme thermophilic 32:43 arg1 bacterium 68:76 a thermophilic, anaerobic, hydrolytic bacterium 30:76 a thermophilic, anaerobic, hydrolytic bacterium 30:76 nov., a thermophilic, anaerobic, hydrolytic bacterium isolated from a deep-sea sample. 24994778 10 70 theme novel 1259:1263 arg1 isolate 1265:1271 the novel isolate 1255:1271 the novel isolate 1255:1271 Based on the phylogenetic analysis and physiological properties of the novel isolate we propose a novel species of the genus Thermosipho, Thermosipho activus sp. 24994778 3 71 theme isolate 340:346 arg1 Cells 321:325 Cells 321:325 Cells of the novel isolate 321:346 Cells of the novel isolate were rods, 0.3-0.8 µm in width and 1.5-10 µm in length, surrounded by a sheath-like structure (toga). 24994778 2 72 attach isolated 213:220 arg2 Rift-s3 197:203 strain Rift-s3 190:203 strain Rift-s3(T) 190:206 A novel obligately anaerobic, extremely thermophilic, organotrophic bacterium, strain Rift-s3(T), was isolated from a deep-sea sample containing Riftia pachyptila sheath from Guaymas Basin, Gulf of California. 24994778 2 72 attach isolated 213:220 arg2 bacterium 179:187 A novel obligately anaerobic, extremely thermophilic, organotrophic bacterium 111:187 A novel obligately anaerobic, extremely thermophilic, organotrophic bacterium 111:187 A novel obligately anaerobic, extremely thermophilic, organotrophic bacterium, strain Rift-s3(T), was isolated from a deep-sea sample containing Riftia pachyptila sheath from Guaymas Basin, Gulf of California. 24994778 2 72 attach isolated 213:220 arg1 sample 238:243 a deep-sea sample 227:243 a deep-sea sample containing Riftia pachyptila sheath from Guaymas Basin, Gulf of California 227:318 A novel obligately anaerobic, extremely thermophilic, organotrophic bacterium, strain Rift-s3(T), was isolated from a deep-sea sample containing Riftia pachyptila sheath from Guaymas Basin, Gulf of California. 29932601 8 0 from fibers 1231:1236 arg1 lesions 1257:1263 lesions 1257:1263 lesions 1257:1263 Collagenous fibers and macrophages in lesions were detected by sirius red staining and immunological histological chemistry to evaluate the atherosclerotic plaque stability. 29932601 12 1 theme model（P 1755:1761 arg1 0.01） 1765:1769 model（P < 0.01） 1755:1769 model（P < 0.01） 1755:1769 Serum TG level was reduced by Mai Shu (1, 2, 4 g·kg-1) compared to model（P < 0.01）. 29932601 17 2 theme Shu 2400:2402 arg1 effect 2386:2391 The effect 2382:2391 The effect of Mai Shu 2382:2402 The effect of Mai Shu may be associated with the decrease of macrophages in plaque. 29932601 11 3 theme Serum 1593:1597 arg1 level 1602:1606 Serum TC level 1593:1606 Serum TC level 1593:1606 Serum TC level was decreased by Mai Shu (4 g·kg-1, P < 0.001) compared to the untreated model. 29932601 15 4 theme Collagenous 2083:2093 arg1 fibers 2095:2100 Collagenous fibers 2083:2100 Collagenous fibers in lesions 2083:2111 Collagenous fibers in lesions were observationally increased by Mai Shu (1, 2 g·kg-1) and macrophages were decreased (2, 4 g·kg-1) compared to model. 29932601 16 5 theme serum 2299:2303 arg1 levels 2311:2316 the serum lipid levels 2295:2316 the serum lipid levels 2295:2316 These results demonstrate that Mai Shu can obviously decrease the serum lipid levels and the risk of leukocyte-endothelial adhesion in ApoE-/- mice. 29932601 14 6 theme Shu 2011:2013 arg1 group 2037:2041 Mai Shu (4 g·kg-1, P < 0.001) group 2007:2041 Mai Shu (4 g·kg-1, P < 0.001) group 2007:2041 Rolling velocity of white blood cells of Mai Shu (4 g·kg-1, P < 0.001) group was increased over the untreated model. 29932601 1 7 from formation 301:309 arg1 mice 377:380 apolipoprotein E knock-out (ApoE-/-) mice 340:380 apolipoprotein E knock-out (ApoE-/-) mice 340:380 The research aimed to investigate the suppression effect of Mai Shu which contains hawthorn, hippophae, medlar, phytosterols（β-sitosterol, stigmasterol and campesterol）, β-glucan and lycopeneon formation of atherosclerotic plaque in apolipoprotein E knock-out (ApoE-/-) mice. 29932601 17 8 theme macrophages 2443:2453 arg1 decrease 2431:2438 the decrease 2427:2438 the decrease of macrophages in plaque 2427:2463 The effect of Mai Shu may be associated with the decrease of macrophages in plaque. 29932601 7 9 theme mesenteric 1132:1141 arg1 artery 1143:1148 mesenteric artery 1132:1148 mesenteric artery of mice 1132:1156 Intravital fluorescence microscopic system was used to evaluate the leukocyte-endothelial adhesion in mesenteric artery of mice by detecting the rolling velocity of white blood cells（WBC）. 29932601 7 10 theme cells（WBC） 1207:1216 arg1 velocity 1183:1190 the rolling velocity 1171:1190 the rolling velocity of white blood cells（WBC） 1171:1216 Intravital fluorescence microscopic system was used to evaluate the leukocyte-endothelial adhesion in mesenteric artery of mice by detecting the rolling velocity of white blood cells（WBC）. 29932601 5 11 theme high 852:855 arg1 lipoprotein 865:875 high density lipoprotein 852:875 high density lipoprotein cholesterol（HDL-C） level 852:900 At the end of administration, the blood of mice was collected for tests of the serum total cholesterol（TC）, total triglyceride（TG） and high density lipoprotein cholesterol（HDL-C） level. 29932601 8 12 theme Collagenous 1219:1229 arg1 fibers 1231:1236 Collagenous fibers 1219:1236 Collagenous fibers 1219:1236 Collagenous fibers and macrophages in lesions were detected by sirius red staining and immunological histological chemistry to evaluate the atherosclerotic plaque stability. 29932601 8 13 from macrophages 1242:1252 arg1 lesions 1257:1263 lesions 1257:1263 lesions 1257:1263 Collagenous fibers and macrophages in lesions were detected by sirius red staining and immunological histological chemistry to evaluate the atherosclerotic plaque stability. 29932601 4 14 theme intragastric 671:682 arg1 route 684:688 intragastric route 671:688 intragastric route for 10 weeks continuously 671:714 The mice were administrated with Mai Shu (1, 2, 4 g·kg-1·d-1) or other contrast materials by intragastric route for 10 weeks continuously. 29932601 14 15 theme blood 1992:1996 arg1 cells 1998:2002 white blood cells 1986:2002 white blood cells of Mai Shu (4 g·kg-1, P < 0.001) group 1986:2041 Rolling velocity of white blood cells of Mai Shu (4 g·kg-1, P < 0.001) group was increased over the untreated model. 29932601 1 16 theme Shu 171:173 arg1 effect 157:162 the suppression effect 141:162 the suppression effect of Mai Shu which contains hawthorn, hippophae, medlar, phytosterols（β-sitosterol, stigmasterol and campesterol）, β-glucan and lycopeneon formation of atherosclerotic plaque in apolipoprotein E knock-out (ApoE-/-) mice 141:380 The research aimed to investigate the suppression effect of Mai Shu which contains hawthorn, hippophae, medlar, phytosterols（β-sitosterol, stigmasterol and campesterol）, β-glucan and lycopeneon formation of atherosclerotic plaque in apolipoprotein E knock-out (ApoE-/-) mice. 29932601 14 17 theme group 2037:2041 arg1 cells 1998:2002 white blood cells 1986:2002 white blood cells of Mai Shu (4 g·kg-1, P < 0.001) group 1986:2041 Rolling velocity of white blood cells of Mai Shu (4 g·kg-1, P < 0.001) group was increased over the untreated model. 29932601 16 18 theme leukocyte-endothelial 2334:2354 arg1 adhesion 2356:2363 leukocyte-endothelial adhesion 2334:2363 leukocyte-endothelial adhesion 2334:2363 These results demonstrate that Mai Shu can obviously decrease the serum lipid levels and the risk of leukocyte-endothelial adhesion in ApoE-/- mice. 29932601 11 19 dep < 1646:1646 arg1 g·kg-1 1636:1641 4 g·kg-1 1634:1641 4 g·kg-1 1634:1641 Serum TC level was decreased by Mai Shu (4 g·kg-1, P < 0.001) compared to the untreated model. 29932601 4 20 theme other 643:647 arg1 materials 658:666 other contrast materials 643:666 other contrast materials 643:666 The mice were administrated with Mai Shu (1, 2, 4 g·kg-1·d-1) or other contrast materials by intragastric route for 10 weeks continuously. 29932601 14 21 theme Rolling 1966:1972 arg1 velocity 1974:1981 Rolling velocity 1966:1981 Rolling velocity of white blood cells of Mai Shu (4 g·kg-1, P < 0.001) group 1966:2041 Rolling velocity of white blood cells of Mai Shu (4 g·kg-1, P < 0.001) group was increased over the untreated model. 29932601 1 22 from hawthorn 190:197 arg1 mice 377:380 apolipoprotein E knock-out (ApoE-/-) mice 340:380 apolipoprotein E knock-out (ApoE-/-) mice 340:380 The research aimed to investigate the suppression effect of Mai Shu which contains hawthorn, hippophae, medlar, phytosterols（β-sitosterol, stigmasterol and campesterol）, β-glucan and lycopeneon formation of atherosclerotic plaque in apolipoprotein E knock-out (ApoE-/-) mice. 29932601 15 23 from fibers 2095:2100 arg1 lesions 2105:2111 lesions 2105:2111 lesions 2105:2111 Collagenous fibers in lesions were observationally increased by Mai Shu (1, 2 g·kg-1) and macrophages were decreased (2, 4 g·kg-1) compared to model. 29932601 1 24 from hippophae 200:208 arg1 mice 377:380 apolipoprotein E knock-out (ApoE-/-) mice 340:380 apolipoprotein E knock-out (ApoE-/-) mice 340:380 The research aimed to investigate the suppression effect of Mai Shu which contains hawthorn, hippophae, medlar, phytosterols（β-sitosterol, stigmasterol and campesterol）, β-glucan and lycopeneon formation of atherosclerotic plaque in apolipoprotein E knock-out (ApoE-/-) mice. 29932601 13 25 from Area 1772:1775 arg1 aorta 1807:1811 aorta 1807:1811 aorta 1807:1811 Area of atherosclerotic lesions in aorta and aortic root was decreased in Mai Shu group (aorta: 1 g·kg-1, P < 0.05; 2 g·kg-1, P < 0.01; 4 g·kg-1, P < 0.001; aortic root: 2, 4 g·kg-1, P < 0.01). 29932601 13 25 from Area 1772:1775 arg1 root 1824:1827 aortic root 1817:1827 aortic root 1817:1827 Area of atherosclerotic lesions in aorta and aortic root was decreased in Mai Shu group (aorta: 1 g·kg-1, P < 0.05; 2 g·kg-1, P < 0.01; 4 g·kg-1, P < 0.001; aortic root: 2, 4 g·kg-1, P < 0.01). 29932601 6 26 theme aortic 940:945 arg1 root 947:950 aortic root 940:950 aortic root 940:950 Atherosclerotic lesions in aorta and aortic root were assessed by calculating the relative area of lesions（oil red O stained）. 29932601 2 27 used used 457:460 arg2 methods 444:450 Liquid chromatography-ultravioletmass spectrometry（LC-UV-MC） methods 383:450 Liquid chromatography-ultravioletmass spectrometry（LC-UV-MC） methods 383:450 Liquid chromatography-ultravioletmass spectrometry（LC-UV-MC） methods were used to analyze the main chemical composition of Mai Shu. 29932601 7 28 theme microscopic 1054:1064 arg1 system 1066:1071 Intravital fluorescence microscopic system 1030:1071 Intravital fluorescence microscopic system 1030:1071 Intravital fluorescence microscopic system was used to evaluate the leukocyte-endothelial adhesion in mesenteric artery of mice by detecting the rolling velocity of white blood cells（WBC）. 29932601 8 29 theme plaque 1375:1380 arg1 stability 1382:1390 the atherosclerotic plaque stability 1355:1390 the atherosclerotic plaque stability 1355:1390 Collagenous fibers and macrophages in lesions were detected by sirius red staining and immunological histological chemistry to evaluate the atherosclerotic plaque stability. 29932601 0 30 theme atherosclerotic 47:61 arg1 plaque 63:68 atherosclerotic plaque 47:68 atherosclerotic plaque of apolipoprotein E knock-out mice 47:103 [Suppression effect of Mai Shu on formation of atherosclerotic plaque of apolipoprotein E knock-out mice]. 29932601 1 31 theme plaque 330:335 arg1 formation 301:309 lycopeneon formation 290:309 lycopeneon formation 290:309 The research aimed to investigate the suppression effect of Mai Shu which contains hawthorn, hippophae, medlar, phytosterols（β-sitosterol, stigmasterol and campesterol）, β-glucan and lycopeneon formation of atherosclerotic plaque in apolipoprotein E knock-out (ApoE-/-) mice. 29932601 1 31 theme plaque 330:335 arg1 hippophae 200:208 hippophae 200:208 hippophae 200:208 The research aimed to investigate the suppression effect of Mai Shu which contains hawthorn, hippophae, medlar, phytosterols（β-sitosterol, stigmasterol and campesterol）, β-glucan and lycopeneon formation of atherosclerotic plaque in apolipoprotein E knock-out (ApoE-/-) mice. 29932601 1 31 theme plaque 330:335 arg1 medlar 211:216 medlar 211:216 medlar 211:216 The research aimed to investigate the suppression effect of Mai Shu which contains hawthorn, hippophae, medlar, phytosterols（β-sitosterol, stigmasterol and campesterol）, β-glucan and lycopeneon formation of atherosclerotic plaque in apolipoprotein E knock-out (ApoE-/-) mice. 29932601 1 31 theme plaque 330:335 arg1 campesterol） 263:274 campesterol） 263:274 campesterol） 263:274 The research aimed to investigate the suppression effect of Mai Shu which contains hawthorn, hippophae, medlar, phytosterols（β-sitosterol, stigmasterol and campesterol）, β-glucan and lycopeneon formation of atherosclerotic plaque in apolipoprotein E knock-out (ApoE-/-) mice. 29932601 1 31 theme plaque 330:335 arg1 β-glucan 277:284 β-glucan 277:284 β-glucan 277:284 The research aimed to investigate the suppression effect of Mai Shu which contains hawthorn, hippophae, medlar, phytosterols（β-sitosterol, stigmasterol and campesterol）, β-glucan and lycopeneon formation of atherosclerotic plaque in apolipoprotein E knock-out (ApoE-/-) mice. 29932601 1 31 theme plaque 330:335 arg1 hawthorn 190:197 hawthorn 190:197 hawthorn 190:197 The research aimed to investigate the suppression effect of Mai Shu which contains hawthorn, hippophae, medlar, phytosterols（β-sitosterol, stigmasterol and campesterol）, β-glucan and lycopeneon formation of atherosclerotic plaque in apolipoprotein E knock-out (ApoE-/-) mice. 29932601 1 31 theme plaque 330:335 arg1 phytosterols（β-sitosterol 219:243 phytosterols（β-sitosterol 219:243 phytosterols（β-sitosterol 219:243 The research aimed to investigate the suppression effect of Mai Shu which contains hawthorn, hippophae, medlar, phytosterols（β-sitosterol, stigmasterol and campesterol）, β-glucan and lycopeneon formation of atherosclerotic plaque in apolipoprotein E knock-out (ApoE-/-) mice. 29932601 1 31 theme plaque 330:335 arg1 stigmasterol 246:257 stigmasterol 246:257 stigmasterol 246:257 The research aimed to investigate the suppression effect of Mai Shu which contains hawthorn, hippophae, medlar, phytosterols（β-sitosterol, stigmasterol and campesterol）, β-glucan and lycopeneon formation of atherosclerotic plaque in apolipoprotein E knock-out (ApoE-/-) mice. 29932601 7 32 theme white 1195:1199 arg1 cells（WBC） 1207:1216 white blood cells（WBC） 1195:1216 white blood cells（WBC） 1195:1216 Intravital fluorescence microscopic system was used to evaluate the leukocyte-endothelial adhesion in mesenteric artery of mice by detecting the rolling velocity of white blood cells（WBC）. 29932601 12 33 theme TG 1694:1695 arg1 level 1697:1701 Serum TG level 1688:1701 Serum TG level 1688:1701 Serum TG level was reduced by Mai Shu (1, 2, 4 g·kg-1) compared to model（P < 0.01）. 29932601 6 34 theme O 1018:1018 arg1 stained） 1020:1027 lesions（oil red O stained） 1002:1027 lesions（oil red O stained） 1002:1027 Atherosclerotic lesions in aorta and aortic root were assessed by calculating the relative area of lesions（oil red O stained）. 29932601 5 35 theme mice 760:763 arg1 blood 751:755 the blood 747:755 the blood of mice 747:763 At the end of administration, the blood of mice was collected for tests of the serum total cholesterol（TC）, total triglyceride（TG） and high density lipoprotein cholesterol（HDL-C） level. 29932601 1 36 theme apolipoprotein 340:353 arg1 mice 377:380 apolipoprotein E knock-out (ApoE-/-) mice 340:380 apolipoprotein E knock-out (ApoE-/-) mice 340:380 The research aimed to investigate the suppression effect of Mai Shu which contains hawthorn, hippophae, medlar, phytosterols（β-sitosterol, stigmasterol and campesterol）, β-glucan and lycopeneon formation of atherosclerotic plaque in apolipoprotein E knock-out (ApoE-/-) mice. 29932601 16 37 from levels 2311:2316 arg1 mice 2376:2379 ApoE-/- mice 2368:2379 ApoE-/- mice 2368:2379 These results demonstrate that Mai Shu can obviously decrease the serum lipid levels and the risk of leukocyte-endothelial adhesion in ApoE-/- mice. 29932601 1 38 theme suppression 145:155 arg1 effect 157:162 the suppression effect 141:162 the suppression effect of Mai Shu which contains hawthorn, hippophae, medlar, phytosterols（β-sitosterol, stigmasterol and campesterol）, β-glucan and lycopeneon formation of atherosclerotic plaque in apolipoprotein E knock-out (ApoE-/-) mice 141:380 The research aimed to investigate the suppression effect of Mai Shu which contains hawthorn, hippophae, medlar, phytosterols（β-sitosterol, stigmasterol and campesterol）, β-glucan and lycopeneon formation of atherosclerotic plaque in apolipoprotein E knock-out (ApoE-/-) mice. 29932601 6 39 theme lesions（oil 1002:1012 arg1 stained） 1020:1027 lesions（oil red O stained） 1002:1027 lesions（oil red O stained） 1002:1027 Atherosclerotic lesions in aorta and aortic root were assessed by calculating the relative area of lesions（oil red O stained）. 29932601 13 40 theme Shu 1850:1852 arg1 group 1854:1858 Mai Shu group 1846:1858 Mai Shu group 1846:1858 Area of atherosclerotic lesions in aorta and aortic root was decreased in Mai Shu group (aorta: 1 g·kg-1, P < 0.05; 2 g·kg-1, P < 0.01; 4 g·kg-1, P < 0.001; aortic root: 2, 4 g·kg-1, P < 0.01). 29932601 0 41 theme E 88:88 arg1 mice 100:103 apolipoprotein E knock-out mice 73:103 apolipoprotein E knock-out mice 73:103 [Suppression effect of Mai Shu on formation of atherosclerotic plaque of apolipoprotein E knock-out mice]. 29932601 1 42 theme knock-out 357:365 arg1 mice 377:380 apolipoprotein E knock-out (ApoE-/-) mice 340:380 apolipoprotein E knock-out (ApoE-/-) mice 340:380 The research aimed to investigate the suppression effect of Mai Shu which contains hawthorn, hippophae, medlar, phytosterols（β-sitosterol, stigmasterol and campesterol）, β-glucan and lycopeneon formation of atherosclerotic plaque in apolipoprotein E knock-out (ApoE-/-) mice. 29932601 13 43 theme aortic 1817:1822 arg1 root 1824:1827 aortic root 1817:1827 aortic root 1817:1827 Area of atherosclerotic lesions in aorta and aortic root was decreased in Mai Shu group (aorta: 1 g·kg-1, P < 0.05; 2 g·kg-1, P < 0.01; 4 g·kg-1, P < 0.001; aortic root: 2, 4 g·kg-1, P < 0.01). 29932601 2 44 theme chromatography-ultravioletmass 390:419 arg1 methods 444:450 Liquid chromatography-ultravioletmass spectrometry（LC-UV-MC） methods 383:450 Liquid chromatography-ultravioletmass spectrometry（LC-UV-MC） methods 383:450 Liquid chromatography-ultravioletmass spectrometry（LC-UV-MC） methods were used to analyze the main chemical composition of Mai Shu. 29932601 0 45 theme mice 100:103 arg1 plaque 63:68 atherosclerotic plaque 47:68 atherosclerotic plaque of apolipoprotein E knock-out mice 47:103 [Suppression effect of Mai Shu on formation of atherosclerotic plaque of apolipoprotein E knock-out mice]. 29932601 1 46 theme ApoE-/- 368:374 arg1 mice 377:380 apolipoprotein E knock-out (ApoE-/-) mice 340:380 apolipoprotein E knock-out (ApoE-/-) mice 340:380 The research aimed to investigate the suppression effect of Mai Shu which contains hawthorn, hippophae, medlar, phytosterols（β-sitosterol, stigmasterol and campesterol）, β-glucan and lycopeneon formation of atherosclerotic plaque in apolipoprotein E knock-out (ApoE-/-) mice. 29932601 2 47 theme main 477:480 arg1 composition 491:501 the main chemical composition 473:501 the main chemical composition of Mai Shu 473:512 Liquid chromatography-ultravioletmass spectrometry（LC-UV-MC） methods were used to analyze the main chemical composition of Mai Shu. 29932601 10 48 theme lipid 1513:1517 arg1 level 1519:1523 The serum lipid level 1503:1523 The serum lipid level of model animals 1503:1540 The serum lipid level of model animals was significantly higher than the control animals. 29932601 10 48 theme lipid 1513:1517 arg1 higher 1560:1565 higher 1560:1565 higher 1560:1565 The serum lipid level of model animals was significantly higher than the control animals. 29932601 0 49 theme [Suppression 0:11 arg1 effect 13:18 [Suppression effect 0:18 [Suppression effect of Mai Shu on formation of atherosclerotic plaque of apolipoprotein E knock-out mice 0:103 [Suppression effect of Mai Shu on formation of atherosclerotic plaque of apolipoprotein E knock-out mice]. 29932601 7 50 from adhesion 1120:1127 arg1 artery 1143:1148 mesenteric artery 1132:1148 mesenteric artery of mice 1132:1156 Intravital fluorescence microscopic system was used to evaluate the leukocyte-endothelial adhesion in mesenteric artery of mice by detecting the rolling velocity of white blood cells（WBC）. 29932601 13 51 theme lesions 1796:1802 arg1 Area 1772:1775 Area 1772:1775 Area of atherosclerotic lesions in aorta and aortic root 1772:1827 Area of atherosclerotic lesions in aorta and aortic root was decreased in Mai Shu group (aorta: 1 g·kg-1, P < 0.05; 2 g·kg-1, P < 0.01; 4 g·kg-1, P < 0.001; aortic root: 2, 4 g·kg-1, P < 0.01). 29932601 5 52 theme total 802:806 arg1 cholesterol（TC） 808:822 the serum total cholesterol（TC） 792:822 the serum total cholesterol（TC） 792:822 At the end of administration, the blood of mice was collected for tests of the serum total cholesterol（TC）, total triglyceride（TG） and high density lipoprotein cholesterol（HDL-C） level. 29932601 5 52 theme total 802:806 arg1 triglyceride（TG） 831:846 total triglyceride（TG） 825:846 total triglyceride（TG） 825:846 At the end of administration, the blood of mice was collected for tests of the serum total cholesterol（TC）, total triglyceride（TG） and high density lipoprotein cholesterol（HDL-C） level. 29932601 5 52 theme total 802:806 arg1 level 896:900 high density lipoprotein cholesterol（HDL-C） level 852:900 high density lipoprotein cholesterol（HDL-C） level 852:900 At the end of administration, the blood of mice was collected for tests of the serum total cholesterol（TC）, total triglyceride（TG） and high density lipoprotein cholesterol（HDL-C） level. 29932601 10 53 theme animals 1534:1540 arg1 level 1519:1523 The serum lipid level 1503:1523 The serum lipid level of model animals 1503:1540 The serum lipid level of model animals was significantly higher than the control animals. 29932601 10 53 theme animals 1534:1540 arg1 higher 1560:1565 higher 1560:1565 higher 1560:1565 The serum lipid level of model animals was significantly higher than the control animals. 29932601 0 54 theme Shu 27:29 arg1 effect 13:18 [Suppression effect 0:18 [Suppression effect of Mai Shu on formation of atherosclerotic plaque of apolipoprotein E knock-out mice 0:103 [Suppression effect of Mai Shu on formation of atherosclerotic plaque of apolipoprotein E knock-out mice]. 29932601 1 55 theme lycopeneon 290:299 arg1 formation 301:309 lycopeneon formation 290:309 lycopeneon formation 290:309 The research aimed to investigate the suppression effect of Mai Shu which contains hawthorn, hippophae, medlar, phytosterols（β-sitosterol, stigmasterol and campesterol）, β-glucan and lycopeneon formation of atherosclerotic plaque in apolipoprotein E knock-out (ApoE-/-) mice. 29932601 13 56 from aorta 1807:1811 arg1 Area 1772:1775 Area 1772:1775 Area of atherosclerotic lesions in aorta and aortic root 1772:1827 Area of atherosclerotic lesions in aorta and aortic root was decreased in Mai Shu group (aorta: 1 g·kg-1, P < 0.05; 2 g·kg-1, P < 0.01; 4 g·kg-1, P < 0.001; aortic root: 2, 4 g·kg-1, P < 0.01). 29932601 10 57 theme control 1576:1582 arg1 animals 1584:1590 the control animals 1572:1590 the control animals 1572:1590 The serum lipid level of model animals was significantly higher than the control animals. 29932601 3 58 theme Atherosclerotic 515:529 arg1 models 536:541 Atherosclerotic mice models 515:541 Atherosclerotic mice models 515:541 Atherosclerotic mice models were established by high-fat diet. 29932601 9 59 theme various 1430:1436 arg1 ） 1500:1500 various flavonoids（9.5%）, phytosterols（23.8%） and polysaccharides（8.9%） 1430:1500 various flavonoids（9.5%）, phytosterols（23.8%） and polysaccharides（8.9%） 1430:1500 Results showed that Mai Shu contains various flavonoids（9.5%）, phytosterols（23.8%） and polysaccharides（8.9%）. 29932601 13 60 from lesions 1796:1802 arg1 aorta 1807:1811 aorta 1807:1811 aorta 1807:1811 Area of atherosclerotic lesions in aorta and aortic root was decreased in Mai Shu group (aorta: 1 g·kg-1, P < 0.05; 2 g·kg-1, P < 0.01; 4 g·kg-1, P < 0.001; aortic root: 2, 4 g·kg-1, P < 0.01). 29932601 13 60 from lesions 1796:1802 arg1 root 1824:1827 aortic root 1817:1827 aortic root 1817:1827 Area of atherosclerotic lesions in aorta and aortic root was decreased in Mai Shu group (aorta: 1 g·kg-1, P < 0.05; 2 g·kg-1, P < 0.01; 4 g·kg-1, P < 0.001; aortic root: 2, 4 g·kg-1, P < 0.01). 29932601 9 61 theme % 1452:1452 arg1 ） 1500:1500 various flavonoids（9.5%）, phytosterols（23.8%） and polysaccharides（8.9%） 1430:1500 various flavonoids（9.5%）, phytosterols（23.8%） and polysaccharides（8.9%） 1430:1500 Results showed that Mai Shu contains various flavonoids（9.5%）, phytosterols（23.8%） and polysaccharides（8.9%）. 29932601 12 62 theme < 1763:1763 arg1 0.01） 1765:1769 model（P < 0.01） 1755:1769 model（P < 0.01） 1755:1769 Serum TG level was reduced by Mai Shu (1, 2, 4 g·kg-1) compared to model（P < 0.01）. 29932601 7 63 theme mice 1153:1156 arg1 artery 1143:1148 mesenteric artery 1132:1148 mesenteric artery of mice 1132:1156 Intravital fluorescence microscopic system was used to evaluate the leukocyte-endothelial adhesion in mesenteric artery of mice by detecting the rolling velocity of white blood cells（WBC）. 29932601 9 64 theme % 1473:1473 arg1 ） 1500:1500 various flavonoids（9.5%）, phytosterols（23.8%） and polysaccharides（8.9%） 1430:1500 various flavonoids（9.5%）, phytosterols（23.8%） and polysaccharides（8.9%） 1430:1500 Results showed that Mai Shu contains various flavonoids（9.5%）, phytosterols（23.8%） and polysaccharides（8.9%）. 29932601 1 65 from campesterol） 263:274 arg1 mice 377:380 apolipoprotein E knock-out (ApoE-/-) mice 340:380 apolipoprotein E knock-out (ApoE-/-) mice 340:380 The research aimed to investigate the suppression effect of Mai Shu which contains hawthorn, hippophae, medlar, phytosterols（β-sitosterol, stigmasterol and campesterol）, β-glucan and lycopeneon formation of atherosclerotic plaque in apolipoprotein E knock-out (ApoE-/-) mice. 29932601 13 66 dep aorta 1861:1865 arg1 < 1900:1900 P < 0.01 1898:1905 P < 0.01 1898:1905 Area of atherosclerotic lesions in aorta and aortic root was decreased in Mai Shu group (aorta: 1 g·kg-1, P < 0.05; 2 g·kg-1, P < 0.01; 4 g·kg-1, P < 0.001; aortic root: 2, 4 g·kg-1, P < 0.01). 29932601 13 66 dep aorta 1861:1865 arg1 < 1957:1957 P < 0.01 1955:1962 P < 0.01 1955:1962 Area of atherosclerotic lesions in aorta and aortic root was decreased in Mai Shu group (aorta: 1 g·kg-1, P < 0.05; 2 g·kg-1, P < 0.01; 4 g·kg-1, P < 0.001; aortic root: 2, 4 g·kg-1, P < 0.01). 29932601 13 66 dep aorta 1861:1865 arg1 P 1918:1918 P < 0.001 1918:1926 P < 0.001 1918:1926 Area of atherosclerotic lesions in aorta and aortic root was decreased in Mai Shu group (aorta: 1 g·kg-1, P < 0.05; 2 g·kg-1, P < 0.01; 4 g·kg-1, P < 0.001; aortic root: 2, 4 g·kg-1, P < 0.01). 29932601 13 66 dep aorta 1861:1865 arg1 < 1880:1880 P < 0.05 1878:1885 P < 0.05 1878:1885 Area of atherosclerotic lesions in aorta and aortic root was decreased in Mai Shu group (aorta: 1 g·kg-1, P < 0.05; 2 g·kg-1, P < 0.01; 4 g·kg-1, P < 0.001; aortic root: 2, 4 g·kg-1, P < 0.01). 29932601 13 66 dep aorta 1861:1865 arg1 g·kg-1 1947:1952 4 g·kg-1 1945:1952 4 g·kg-1 1945:1952 Area of atherosclerotic lesions in aorta and aortic root was decreased in Mai Shu group (aorta: 1 g·kg-1, P < 0.05; 2 g·kg-1, P < 0.01; 4 g·kg-1, P < 0.001; aortic root: 2, 4 g·kg-1, P < 0.01). 29932601 13 66 dep aorta 1861:1865 arg1 g·kg-1 1870:1875 1 g·kg-1 1868:1875 1 g·kg-1 1868:1875 Area of atherosclerotic lesions in aorta and aortic root was decreased in Mai Shu group (aorta: 1 g·kg-1, P < 0.05; 2 g·kg-1, P < 0.01; 4 g·kg-1, P < 0.001; aortic root: 2, 4 g·kg-1, P < 0.01). 29932601 13 66 dep aorta 1861:1865 arg1 g·kg-1 1910:1915 4 g·kg-1 1908:1915 4 g·kg-1 1908:1915 Area of atherosclerotic lesions in aorta and aortic root was decreased in Mai Shu group (aorta: 1 g·kg-1, P < 0.05; 2 g·kg-1, P < 0.01; 4 g·kg-1, P < 0.001; aortic root: 2, 4 g·kg-1, P < 0.01). 29932601 13 66 dep aorta 1861:1865 arg1 g·kg-1 1890:1895 2 g·kg-1 1888:1895 2 g·kg-1 1888:1895 Area of atherosclerotic lesions in aorta and aortic root was decreased in Mai Shu group (aorta: 1 g·kg-1, P < 0.05; 2 g·kg-1, P < 0.01; 4 g·kg-1, P < 0.001; aortic root: 2, 4 g·kg-1, P < 0.01). 29932601 13 66 dep aorta 1861:1865 arg1 root 1936:1939 aortic root 1929:1939 aortic root 1929:1939 Area of atherosclerotic lesions in aorta and aortic root was decreased in Mai Shu group (aorta: 1 g·kg-1, P < 0.05; 2 g·kg-1, P < 0.01; 4 g·kg-1, P < 0.001; aortic root: 2, 4 g·kg-1, P < 0.01). 29932601 11 67 theme TC 1599:1600 arg1 level 1602:1606 Serum TC level 1593:1606 Serum TC level 1593:1606 Serum TC level was decreased by Mai Shu (4 g·kg-1, P < 0.001) compared to the untreated model. 29932601 6 68 theme Atherosclerotic 903:917 arg1 lesions 919:925 Atherosclerotic lesions 903:925 Atherosclerotic lesions in aorta and aortic root 903:950 Atherosclerotic lesions in aorta and aortic root were assessed by calculating the relative area of lesions（oil red O stained）. 29932601 14 69 dep 0.001 2030:2034 arg1 g·kg-1 2018:2023 4 g·kg-1 2016:2023 4 g·kg-1 2016:2023 Rolling velocity of white blood cells of Mai Shu (4 g·kg-1, P < 0.001) group was increased over the untreated model. 29932601 14 69 dep 0.001 2030:2034 arg1 < 2028:2028 < 2028:2028 < 2028:2028 Rolling velocity of white blood cells of Mai Shu (4 g·kg-1, P < 0.001) group was increased over the untreated model. 29932601 1 70 from β-glucan 277:284 arg1 mice 377:380 apolipoprotein E knock-out (ApoE-/-) mice 340:380 apolipoprotein E knock-out (ApoE-/-) mice 340:380 The research aimed to investigate the suppression effect of Mai Shu which contains hawthorn, hippophae, medlar, phytosterols（β-sitosterol, stigmasterol and campesterol）, β-glucan and lycopeneon formation of atherosclerotic plaque in apolipoprotein E knock-out (ApoE-/-) mice. 29932601 3 71 theme high-fat 563:570 arg1 diet 572:575 high-fat diet 563:575 high-fat diet 563:575 Atherosclerotic mice models were established by high-fat diet. 29932601 8 72 theme red 1289:1291 arg1 staining 1293:1300 sirius red staining 1282:1300 sirius red staining 1282:1300 Collagenous fibers and macrophages in lesions were detected by sirius red staining and immunological histological chemistry to evaluate the atherosclerotic plaque stability. 29932601 9 73 theme % 1499:1499 arg1 ） 1500:1500 various flavonoids（9.5%）, phytosterols（23.8%） and polysaccharides（8.9%） 1430:1500 various flavonoids（9.5%）, phytosterols（23.8%） and polysaccharides（8.9%） 1430:1500 Results showed that Mai Shu contains various flavonoids（9.5%）, phytosterols（23.8%） and polysaccharides（8.9%）. 29932601 14 74 dep group 2037:2041 arg1 0.001 2030:2034 0.001 2030:2034 0.001 2030:2034 Rolling velocity of white blood cells of Mai Shu (4 g·kg-1, P < 0.001) group was increased over the untreated model. 29932601 4 75 theme contrast 649:656 arg1 materials 658:666 other contrast materials 643:666 other contrast materials 643:666 The mice were administrated with Mai Shu (1, 2, 4 g·kg-1·d-1) or other contrast materials by intragastric route for 10 weeks continuously. 29932601 14 76 theme cells 1998:2002 arg1 velocity 1974:1981 Rolling velocity 1966:1981 Rolling velocity of white blood cells of Mai Shu (4 g·kg-1, P < 0.001) group 1966:2041 Rolling velocity of white blood cells of Mai Shu (4 g·kg-1, P < 0.001) group was increased over the untreated model. 29932601 11 77 theme untreated 1671:1679 arg1 model 1681:1685 the untreated model 1667:1685 the untreated model 1667:1685 Serum TC level was decreased by Mai Shu (4 g·kg-1, P < 0.001) compared to the untreated model. 29932601 7 78 theme leukocyte-endothelial 1098:1118 arg1 adhesion 1120:1127 the leukocyte-endothelial adhesion 1094:1127 the leukocyte-endothelial adhesion in mesenteric artery of mice 1094:1156 Intravital fluorescence microscopic system was used to evaluate the leukocyte-endothelial adhesion in mesenteric artery of mice by detecting the rolling velocity of white blood cells（WBC）. 29932601 5 79 theme density 857:863 arg1 lipoprotein 865:875 high density lipoprotein 852:875 high density lipoprotein cholesterol（HDL-C） level 852:900 At the end of administration, the blood of mice was collected for tests of the serum total cholesterol（TC）, total triglyceride（TG） and high density lipoprotein cholesterol（HDL-C） level. 29932601 7 80 used used 1077:1080 arg2 system 1066:1071 Intravital fluorescence microscopic system 1030:1071 Intravital fluorescence microscopic system 1030:1071 Intravital fluorescence microscopic system was used to evaluate the leukocyte-endothelial adhesion in mesenteric artery of mice by detecting the rolling velocity of white blood cells（WBC）. 29932601 6 81 theme relative 985:992 arg1 area 994:997 the relative area 981:997 the relative area of lesions（oil red O stained） 981:1027 Atherosclerotic lesions in aorta and aortic root were assessed by calculating the relative area of lesions（oil red O stained）. 29932601 13 82 dep decreased 1833:1841 arg1 aorta 1861:1865 aorta 1861:1865 aorta 1861:1865 Area of atherosclerotic lesions in aorta and aortic root was decreased in Mai Shu group (aorta: 1 g·kg-1, P < 0.05; 2 g·kg-1, P < 0.01; 4 g·kg-1, P < 0.001; aortic root: 2, 4 g·kg-1, P < 0.01). 29932601 8 83 theme sirius 1282:1287 arg1 staining 1293:1300 sirius red staining 1282:1300 sirius red staining 1282:1300 Collagenous fibers and macrophages in lesions were detected by sirius red staining and immunological histological chemistry to evaluate the atherosclerotic plaque stability. 29932601 14 84 theme white 1986:1990 arg1 cells 1998:2002 white blood cells 1986:2002 white blood cells of Mai Shu (4 g·kg-1, P < 0.001) group 1986:2041 Rolling velocity of white blood cells of Mai Shu (4 g·kg-1, P < 0.001) group was increased over the untreated model. 29932601 1 85 from stigmasterol 246:257 arg1 mice 377:380 apolipoprotein E knock-out (ApoE-/-) mice 340:380 apolipoprotein E knock-out (ApoE-/-) mice 340:380 The research aimed to investigate the suppression effect of Mai Shu which contains hawthorn, hippophae, medlar, phytosterols（β-sitosterol, stigmasterol and campesterol）, β-glucan and lycopeneon formation of atherosclerotic plaque in apolipoprotein E knock-out (ApoE-/-) mice. 29932601 13 86 theme P 1878:1878 arg1 < 1880:1880 P < 0.05 1878:1885 P < 0.05 1878:1885 Area of atherosclerotic lesions in aorta and aortic root was decreased in Mai Shu group (aorta: 1 g·kg-1, P < 0.05; 2 g·kg-1, P < 0.01; 4 g·kg-1, P < 0.001; aortic root: 2, 4 g·kg-1, P < 0.01). 29932601 5 87 theme cholesterol（TC） 808:822 arg1 tests 783:787 tests 783:787 tests of the serum total cholesterol（TC）, total triglyceride（TG） and high density lipoprotein cholesterol（HDL-C） level 783:900 At the end of administration, the blood of mice was collected for tests of the serum total cholesterol（TC）, total triglyceride（TG） and high density lipoprotein cholesterol（HDL-C） level. 29932601 15 88 dep decreased 2190:2198 arg1 g·kg-1 2206:2211 2, 4 g·kg-1 2201:2211 2, 4 g·kg-1 2201:2211 Collagenous fibers in lesions were observationally increased by Mai Shu (1, 2 g·kg-1) and macrophages were decreased (2, 4 g·kg-1) compared to model. 29932601 1 89 from phytosterols（β-sitosterol 219:243 arg1 mice 377:380 apolipoprotein E knock-out (ApoE-/-) mice 340:380 apolipoprotein E knock-out (ApoE-/-) mice 340:380 The research aimed to investigate the suppression effect of Mai Shu which contains hawthorn, hippophae, medlar, phytosterols（β-sitosterol, stigmasterol and campesterol）, β-glucan and lycopeneon formation of atherosclerotic plaque in apolipoprotein E knock-out (ApoE-/-) mice. 29932601 13 90 theme P 1955:1955 arg1 < 1957:1957 P < 0.01 1955:1962 P < 0.01 1955:1962 Area of atherosclerotic lesions in aorta and aortic root was decreased in Mai Shu group (aorta: 1 g·kg-1, P < 0.05; 2 g·kg-1, P < 0.01; 4 g·kg-1, P < 0.001; aortic root: 2, 4 g·kg-1, P < 0.01). 29932601 5 91 theme lipoprotein 865:875 arg1 cholesterol（TC） 808:822 the serum total cholesterol（TC） 792:822 the serum total cholesterol（TC） 792:822 At the end of administration, the blood of mice was collected for tests of the serum total cholesterol（TC）, total triglyceride（TG） and high density lipoprotein cholesterol（HDL-C） level. 29932601 5 91 theme lipoprotein 865:875 arg1 level 896:900 high density lipoprotein cholesterol（HDL-C） level 852:900 high density lipoprotein cholesterol（HDL-C） level 852:900 At the end of administration, the blood of mice was collected for tests of the serum total cholesterol（TC）, total triglyceride（TG） and high density lipoprotein cholesterol（HDL-C） level. 29932601 5 92 theme total 825:829 arg1 cholesterol（TC） 808:822 the serum total cholesterol（TC） 792:822 the serum total cholesterol（TC） 792:822 At the end of administration, the blood of mice was collected for tests of the serum total cholesterol（TC）, total triglyceride（TG） and high density lipoprotein cholesterol（HDL-C） level. 29932601 5 92 theme total 825:829 arg1 triglyceride（TG） 831:846 total triglyceride（TG） 825:846 total triglyceride（TG） 825:846 At the end of administration, the blood of mice was collected for tests of the serum total cholesterol（TC）, total triglyceride（TG） and high density lipoprotein cholesterol（HDL-C） level. 29932601 16 93 theme ApoE-/- 2368:2374 arg1 mice 2376:2379 ApoE-/- mice 2368:2379 ApoE-/- mice 2368:2379 These results demonstrate that Mai Shu can obviously decrease the serum lipid levels and the risk of leukocyte-endothelial adhesion in ApoE-/- mice. 29932601 16 94 theme lipid 2305:2309 arg1 levels 2311:2316 the serum lipid levels 2295:2316 the serum lipid levels 2295:2316 These results demonstrate that Mai Shu can obviously decrease the serum lipid levels and the risk of leukocyte-endothelial adhesion in ApoE-/- mice. 29932601 8 95 theme immunological 1306:1318 arg1 chemistry 1333:1341 immunological histological chemistry 1306:1341 immunological histological chemistry 1306:1341 Collagenous fibers and macrophages in lesions were detected by sirius red staining and immunological histological chemistry to evaluate the atherosclerotic plaque stability. 29932601 1 96 from medlar 211:216 arg1 mice 377:380 apolipoprotein E knock-out (ApoE-/-) mice 340:380 apolipoprotein E knock-out (ApoE-/-) mice 340:380 The research aimed to investigate the suppression effect of Mai Shu which contains hawthorn, hippophae, medlar, phytosterols（β-sitosterol, stigmasterol and campesterol）, β-glucan and lycopeneon formation of atherosclerotic plaque in apolipoprotein E knock-out (ApoE-/-) mice. 29932601 7 97 theme Intravital 1030:1039 arg1 system 1066:1071 Intravital fluorescence microscopic system 1030:1071 Intravital fluorescence microscopic system 1030:1071 Intravital fluorescence microscopic system was used to evaluate the leukocyte-endothelial adhesion in mesenteric artery of mice by detecting the rolling velocity of white blood cells（WBC）. 29932601 7 98 theme fluorescence 1041:1052 arg1 system 1066:1071 Intravital fluorescence microscopic system 1030:1071 Intravital fluorescence microscopic system 1030:1071 Intravital fluorescence microscopic system was used to evaluate the leukocyte-endothelial adhesion in mesenteric artery of mice by detecting the rolling velocity of white blood cells（WBC）. 29932601 15 99 dep Shu 2151:2153 arg1 1 2156:2156 1 2156:2156 1 2156:2156 Collagenous fibers in lesions were observationally increased by Mai Shu (1, 2 g·kg-1) and macrophages were decreased (2, 4 g·kg-1) compared to model. 29932601 15 99 dep Shu 2151:2153 arg1 g·kg-1 2161:2166 2 g·kg-1 2159:2166 2 g·kg-1 2159:2166 Collagenous fibers in lesions were observationally increased by Mai Shu (1, 2 g·kg-1) and macrophages were decreased (2, 4 g·kg-1) compared to model. 29932601 0 100 theme plaque 63:68 arg1 formation 34:42 formation 34:42 formation of atherosclerotic plaque of apolipoprotein E knock-out mice 34:103 [Suppression effect of Mai Shu on formation of atherosclerotic plaque of apolipoprotein E knock-out mice]. 29932601 14 101 theme untreated 2066:2074 arg1 model 2076:2080 the untreated model 2062:2080 the untreated model 2062:2080 Rolling velocity of white blood cells of Mai Shu (4 g·kg-1, P < 0.001) group was increased over the untreated model. 29932601 5 102 theme cholesterol（HDL-C） 877:894 arg1 cholesterol（TC） 808:822 the serum total cholesterol（TC） 792:822 the serum total cholesterol（TC） 792:822 At the end of administration, the blood of mice was collected for tests of the serum total cholesterol（TC）, total triglyceride（TG） and high density lipoprotein cholesterol（HDL-C） level. 29932601 5 102 theme cholesterol（HDL-C） 877:894 arg1 level 896:900 high density lipoprotein cholesterol（HDL-C） level 852:900 high density lipoprotein cholesterol（HDL-C） level 852:900 At the end of administration, the blood of mice was collected for tests of the serum total cholesterol（TC）, total triglyceride（TG） and high density lipoprotein cholesterol（HDL-C） level. 29932601 6 103 theme stained） 1020:1027 arg1 area 994:997 the relative area 981:997 the relative area of lesions（oil red O stained） 981:1027 Atherosclerotic lesions in aorta and aortic root were assessed by calculating the relative area of lesions（oil red O stained）. 29932601 8 104 theme atherosclerotic 1359:1373 arg1 plaque 1375:1380 the atherosclerotic plaque 1355:1380 the atherosclerotic plaque stability 1355:1390 Collagenous fibers and macrophages in lesions were detected by sirius red staining and immunological histological chemistry to evaluate the atherosclerotic plaque stability. 29932601 0 105 theme apolipoprotein 73:86 arg1 E 88:88 apolipoprotein E 73:88 apolipoprotein E knock-out mice 73:103 [Suppression effect of Mai Shu on formation of atherosclerotic plaque of apolipoprotein E knock-out mice]. 29932601 13 106 theme aortic 1929:1934 arg1 g·kg-1 1947:1952 4 g·kg-1 1945:1952 4 g·kg-1 1945:1952 Area of atherosclerotic lesions in aorta and aortic root was decreased in Mai Shu group (aorta: 1 g·kg-1, P < 0.05; 2 g·kg-1, P < 0.01; 4 g·kg-1, P < 0.001; aortic root: 2, 4 g·kg-1, P < 0.01). 29932601 13 106 theme aortic 1929:1934 arg1 root 1936:1939 aortic root 1929:1939 aortic root 1929:1939 Area of atherosclerotic lesions in aorta and aortic root was decreased in Mai Shu group (aorta: 1 g·kg-1, P < 0.05; 2 g·kg-1, P < 0.01; 4 g·kg-1, P < 0.001; aortic root: 2, 4 g·kg-1, P < 0.01). 29932601 12 107 theme Serum 1688:1692 arg1 level 1697:1701 Serum TG level 1688:1701 Serum TG level 1688:1701 Serum TG level was reduced by Mai Shu (1, 2, 4 g·kg-1) compared to model（P < 0.01）. 29932601 6 108 theme red 1014:1016 arg1 stained） 1020:1027 lesions（oil red O stained） 1002:1027 lesions（oil red O stained） 1002:1027 Atherosclerotic lesions in aorta and aortic root were assessed by calculating the relative area of lesions（oil red O stained）. 29932601 2 109 theme Shu 510:512 arg1 composition 491:501 the main chemical composition 473:501 the main chemical composition of Mai Shu 473:512 Liquid chromatography-ultravioletmass spectrometry（LC-UV-MC） methods were used to analyze the main chemical composition of Mai Shu. 29932601 0 110 from effect 13:18 arg1 formation 34:42 formation 34:42 formation of atherosclerotic plaque of apolipoprotein E knock-out mice 34:103 [Suppression effect of Mai Shu on formation of atherosclerotic plaque of apolipoprotein E knock-out mice]. 29932601 13 111 theme Mai 1846:1848 arg1 group 1854:1858 Mai Shu group 1846:1858 Mai Shu group 1846:1858 Area of atherosclerotic lesions in aorta and aortic root was decreased in Mai Shu group (aorta: 1 g·kg-1, P < 0.05; 2 g·kg-1, P < 0.01; 4 g·kg-1, P < 0.001; aortic root: 2, 4 g·kg-1, P < 0.01). 29932601 0 112 theme knock-out 90:98 arg1 mice 100:103 apolipoprotein E knock-out mice 73:103 apolipoprotein E knock-out mice 73:103 [Suppression effect of Mai Shu on formation of atherosclerotic plaque of apolipoprotein E knock-out mice]. 29932601 1 113 theme E 355:355 arg1 mice 377:380 apolipoprotein E knock-out (ApoE-/-) mice 340:380 apolipoprotein E knock-out (ApoE-/-) mice 340:380 The research aimed to investigate the suppression effect of Mai Shu which contains hawthorn, hippophae, medlar, phytosterols（β-sitosterol, stigmasterol and campesterol）, β-glucan and lycopeneon formation of atherosclerotic plaque in apolipoprotein E knock-out (ApoE-/-) mice. 29932601 5 114 theme administration 731:744 arg1 end 724:726 the end 720:726 the end of administration 720:744 At the end of administration, the blood of mice was collected for tests of the serum total cholesterol（TC）, total triglyceride（TG） and high density lipoprotein cholesterol（HDL-C） level. 29932601 2 115 theme Liquid 383:388 arg1 methods 444:450 Liquid chromatography-ultravioletmass spectrometry（LC-UV-MC） methods 383:450 Liquid chromatography-ultravioletmass spectrometry（LC-UV-MC） methods 383:450 Liquid chromatography-ultravioletmass spectrometry（LC-UV-MC） methods were used to analyze the main chemical composition of Mai Shu. 29932601 7 116 theme blood 1201:1205 arg1 cells（WBC） 1207:1216 white blood cells（WBC） 1195:1216 white blood cells（WBC） 1195:1216 Intravital fluorescence microscopic system was used to evaluate the leukocyte-endothelial adhesion in mesenteric artery of mice by detecting the rolling velocity of white blood cells（WBC）. 29932601 13 117 dep root 1936:1939 arg1 2 1942:1942 2 1942:1942 2 1942:1942 Area of atherosclerotic lesions in aorta and aortic root was decreased in Mai Shu group (aorta: 1 g·kg-1, P < 0.05; 2 g·kg-1, P < 0.01; 4 g·kg-1, P < 0.001; aortic root: 2, 4 g·kg-1, P < 0.01). 29932601 10 118 theme serum 1507:1511 arg1 level 1519:1523 The serum lipid level 1503:1523 The serum lipid level of model animals 1503:1540 The serum lipid level of model animals was significantly higher than the control animals. 29932601 10 118 theme serum 1507:1511 arg1 higher 1560:1565 higher 1560:1565 higher 1560:1565 The serum lipid level of model animals was significantly higher than the control animals. 29932601 13 119 theme atherosclerotic 1780:1794 arg1 lesions 1796:1802 atherosclerotic lesions 1780:1802 atherosclerotic lesions in aorta and aortic root 1780:1827 Area of atherosclerotic lesions in aorta and aortic root was decreased in Mai Shu group (aorta: 1 g·kg-1, P < 0.05; 2 g·kg-1, P < 0.01; 4 g·kg-1, P < 0.001; aortic root: 2, 4 g·kg-1, P < 0.01). 29932601 5 120 theme serum 796:800 arg1 cholesterol（TC） 808:822 the serum total cholesterol（TC） 792:822 the serum total cholesterol（TC） 792:822 At the end of administration, the blood of mice was collected for tests of the serum total cholesterol（TC）, total triglyceride（TG） and high density lipoprotein cholesterol（HDL-C） level. 29932601 5 120 theme serum 796:800 arg1 triglyceride（TG） 831:846 total triglyceride（TG） 825:846 total triglyceride（TG） 825:846 At the end of administration, the blood of mice was collected for tests of the serum total cholesterol（TC）, total triglyceride（TG） and high density lipoprotein cholesterol（HDL-C） level. 29932601 5 120 theme serum 796:800 arg1 level 896:900 high density lipoprotein cholesterol（HDL-C） level 852:900 high density lipoprotein cholesterol（HDL-C） level 852:900 At the end of administration, the blood of mice was collected for tests of the serum total cholesterol（TC）, total triglyceride（TG） and high density lipoprotein cholesterol（HDL-C） level. 29932601 7 121 theme rolling 1175:1181 arg1 velocity 1183:1190 the rolling velocity 1171:1190 the rolling velocity of white blood cells（WBC） 1171:1216 Intravital fluorescence microscopic system was used to evaluate the leukocyte-endothelial adhesion in mesenteric artery of mice by detecting the rolling velocity of white blood cells（WBC）. 29932601 8 122 theme histological 1320:1331 arg1 chemistry 1333:1341 immunological histological chemistry 1306:1341 immunological histological chemistry 1306:1341 Collagenous fibers and macrophages in lesions were detected by sirius red staining and immunological histological chemistry to evaluate the atherosclerotic plaque stability. 29932601 10 123 theme model 1528:1532 arg1 animals 1534:1540 model animals 1528:1540 model animals 1528:1540 The serum lipid level of model animals was significantly higher than the control animals. 29932601 2 124 theme spectrometry（LC-UV-MC） 421:442 arg1 methods 444:450 Liquid chromatography-ultravioletmass spectrometry（LC-UV-MC） methods 383:450 Liquid chromatography-ultravioletmass spectrometry（LC-UV-MC） methods 383:450 Liquid chromatography-ultravioletmass spectrometry（LC-UV-MC） methods were used to analyze the main chemical composition of Mai Shu. 29932601 17 125 from decrease 2431:2438 arg1 plaque 2458:2463 plaque 2458:2463 plaque 2458:2463 The effect of Mai Shu may be associated with the decrease of macrophages in plaque. 29932601 13 126 theme < 1920:1920 arg1 P 1918:1918 P < 0.001 1918:1926 P < 0.001 1918:1926 Area of atherosclerotic lesions in aorta and aortic root was decreased in Mai Shu group (aorta: 1 g·kg-1, P < 0.05; 2 g·kg-1, P < 0.01; 4 g·kg-1, P < 0.001; aortic root: 2, 4 g·kg-1, P < 0.01). 29932601 2 127 theme chemical 482:489 arg1 composition 491:501 the main chemical composition 473:501 the main chemical composition of Mai Shu 473:512 Liquid chromatography-ultravioletmass spectrometry（LC-UV-MC） methods were used to analyze the main chemical composition of Mai Shu. 29932601 3 128 theme mice 531:534 arg1 models 536:541 Atherosclerotic mice models 515:541 Atherosclerotic mice models 515:541 Atherosclerotic mice models were established by high-fat diet. 29932601 1 129 theme atherosclerotic 314:328 arg1 plaque 330:335 atherosclerotic plaque 314:335 atherosclerotic plaque 314:335 The research aimed to investigate the suppression effect of Mai Shu which contains hawthorn, hippophae, medlar, phytosterols（β-sitosterol, stigmasterol and campesterol）, β-glucan and lycopeneon formation of atherosclerotic plaque in apolipoprotein E knock-out (ApoE-/-) mice. 29932601 13 130 from root 1824:1827 arg1 Area 1772:1775 Area 1772:1775 Area of atherosclerotic lesions in aorta and aortic root 1772:1827 Area of atherosclerotic lesions in aorta and aortic root was decreased in Mai Shu group (aorta: 1 g·kg-1, P < 0.05; 2 g·kg-1, P < 0.01; 4 g·kg-1, P < 0.001; aortic root: 2, 4 g·kg-1, P < 0.01). 29932601 16 131 from risk 2326:2329 arg1 mice 2376:2379 ApoE-/- mice 2368:2379 ApoE-/- mice 2368:2379 These results demonstrate that Mai Shu can obviously decrease the serum lipid levels and the risk of leukocyte-endothelial adhesion in ApoE-/- mice. 29932601 13 132 theme P 1898:1898 arg1 < 1900:1900 P < 0.01 1898:1905 P < 0.01 1898:1905 Area of atherosclerotic lesions in aorta and aortic root was decreased in Mai Shu group (aorta: 1 g·kg-1, P < 0.05; 2 g·kg-1, P < 0.01; 4 g·kg-1, P < 0.001; aortic root: 2, 4 g·kg-1, P < 0.01). 29932601 1 133 contain contains 181:188 arg2 hawthorn 190:197 hawthorn 190:197 hawthorn 190:197 The research aimed to investigate the suppression effect of Mai Shu which contains hawthorn, hippophae, medlar, phytosterols（β-sitosterol, stigmasterol and campesterol）, β-glucan and lycopeneon formation of atherosclerotic plaque in apolipoprotein E knock-out (ApoE-/-) mice. 29932601 1 133 contain contains 181:188 arg2 phytosterols（β-sitosterol 219:243 phytosterols（β-sitosterol 219:243 phytosterols（β-sitosterol 219:243 The research aimed to investigate the suppression effect of Mai Shu which contains hawthorn, hippophae, medlar, phytosterols（β-sitosterol, stigmasterol and campesterol）, β-glucan and lycopeneon formation of atherosclerotic plaque in apolipoprotein E knock-out (ApoE-/-) mice. 29932601 1 133 contain contains 181:188 arg2 β-glucan 277:284 β-glucan 277:284 β-glucan 277:284 The research aimed to investigate the suppression effect of Mai Shu which contains hawthorn, hippophae, medlar, phytosterols（β-sitosterol, stigmasterol and campesterol）, β-glucan and lycopeneon formation of atherosclerotic plaque in apolipoprotein E knock-out (ApoE-/-) mice. 29932601 1 133 contain contains 181:188 arg2 formation 301:309 lycopeneon formation 290:309 lycopeneon formation 290:309 The research aimed to investigate the suppression effect of Mai Shu which contains hawthorn, hippophae, medlar, phytosterols（β-sitosterol, stigmasterol and campesterol）, β-glucan and lycopeneon formation of atherosclerotic plaque in apolipoprotein E knock-out (ApoE-/-) mice. 29932601 1 133 contain contains 181:188 arg2 stigmasterol 246:257 stigmasterol 246:257 stigmasterol 246:257 The research aimed to investigate the suppression effect of Mai Shu which contains hawthorn, hippophae, medlar, phytosterols（β-sitosterol, stigmasterol and campesterol）, β-glucan and lycopeneon formation of atherosclerotic plaque in apolipoprotein E knock-out (ApoE-/-) mice. 29932601 1 133 contain contains 181:188 arg2 hippophae 200:208 hippophae 200:208 hippophae 200:208 The research aimed to investigate the suppression effect of Mai Shu which contains hawthorn, hippophae, medlar, phytosterols（β-sitosterol, stigmasterol and campesterol）, β-glucan and lycopeneon formation of atherosclerotic plaque in apolipoprotein E knock-out (ApoE-/-) mice. 29932601 1 133 contain contains 181:188 arg1 effect 157:162 the suppression effect 141:162 the suppression effect of Mai Shu which contains hawthorn, hippophae, medlar, phytosterols（β-sitosterol, stigmasterol and campesterol）, β-glucan and lycopeneon formation of atherosclerotic plaque in apolipoprotein E knock-out (ApoE-/-) mice 141:380 The research aimed to investigate the suppression effect of Mai Shu which contains hawthorn, hippophae, medlar, phytosterols（β-sitosterol, stigmasterol and campesterol）, β-glucan and lycopeneon formation of atherosclerotic plaque in apolipoprotein E knock-out (ApoE-/-) mice. 29932601 1 133 contain contains 181:188 arg2 medlar 211:216 medlar 211:216 medlar 211:216 The research aimed to investigate the suppression effect of Mai Shu which contains hawthorn, hippophae, medlar, phytosterols（β-sitosterol, stigmasterol and campesterol）, β-glucan and lycopeneon formation of atherosclerotic plaque in apolipoprotein E knock-out (ApoE-/-) mice. 29932601 16 134 theme adhesion 2356:2363 arg1 levels 2311:2316 the serum lipid levels 2295:2316 the serum lipid levels 2295:2316 These results demonstrate that Mai Shu can obviously decrease the serum lipid levels and the risk of leukocyte-endothelial adhesion in ApoE-/- mice. 29932601 16 134 theme adhesion 2356:2363 arg1 risk 2326:2329 the risk 2322:2329 the risk of leukocyte-endothelial adhesion in ApoE-/- mice 2322:2379 These results demonstrate that Mai Shu can obviously decrease the serum lipid levels and the risk of leukocyte-endothelial adhesion in ApoE-/- mice. 29932601 6 135 from lesions 919:925 arg1 aorta 930:934 aorta 930:934 aorta 930:934 Atherosclerotic lesions in aorta and aortic root were assessed by calculating the relative area of lesions（oil red O stained）. 29932601 6 135 from lesions 919:925 arg1 root 947:950 aortic root 940:950 aortic root 940:950 Atherosclerotic lesions in aorta and aortic root were assessed by calculating the relative area of lesions（oil red O stained）. 29932601 9 136 contain contains 1421:1428 arg2 ） 1500:1500 various flavonoids（9.5%）, phytosterols（23.8%） and polysaccharides（8.9%） 1430:1500 various flavonoids（9.5%）, phytosterols（23.8%） and polysaccharides（8.9%） 1430:1500 Results showed that Mai Shu contains various flavonoids（9.5%）, phytosterols（23.8%） and polysaccharides（8.9%）. 29932601 9 136 contain contains 1421:1428 arg1 Shu 1417:1419 Shu 1417:1419 Shu 1417:1419 Results showed that Mai Shu contains various flavonoids（9.5%）, phytosterols（23.8%） and polysaccharides（8.9%）. 28910556 10 0 theme improved 1700:1707 arg1 osteointegration 1709:1724 improved osteointegration 1700:1724 improved osteointegration 1700:1724 It is believed that incorporating DMP1-C or DSP on the surface of a bone implant may improve the collagen interactions with the implant, thereby facilitating improved osteointegration. 28910556 0 1 from influence 12:20 arg1 denaturation 76:87 denaturation 76:87 denaturation 76:87 Probing the influence of SIBLING proteins on collagen-I fibrillogenesis and denaturation. 28910556 0 1 from influence 12:20 arg1 fibrillogenesis 56:70 collagen-I fibrillogenesis 45:70 collagen-I fibrillogenesis 45:70 Probing the influence of SIBLING proteins on collagen-I fibrillogenesis and denaturation. 28910556 6 2 from role 1063:1066 arg1 processes 1093:1101 these processes 1087:1101 these processes 1087:1101 The role of calcium ions in these processes was also investigated. 28910556 3 3 theme dentin 642:647 arg1 protein 656:662 dentin matrix protein 1 642:664 dentin matrix protein 1 (DMP1-C) 642:673 In this work, bone sialoprotein, osteopontin (OPN), dentin sialoprotein (DSP), dentin phosphoprotein (DPP), C-terminal fragment of dentin matrix protein 1 (DMP1-C), and proteoglycan versions of DSP (DSP-PG) and DMP1 (DMP1-PG) were tested individually to determine their roles in collagen fibrillogenesis and the prevention of denaturation. 28910556 3 3 theme dentin 642:647 arg1 DMP1-C 667:672 DMP1-C 667:672 DMP1-C 667:672 In this work, bone sialoprotein, osteopontin (OPN), dentin sialoprotein (DSP), dentin phosphoprotein (DPP), C-terminal fragment of dentin matrix protein 1 (DMP1-C), and proteoglycan versions of DSP (DSP-PG) and DMP1 (DMP1-PG) were tested individually to determine their roles in collagen fibrillogenesis and the prevention of denaturation. 28910556 3 4 theme C-terminal 619:628 arg1 fragment 630:637 C-terminal fragment 619:637 C-terminal fragment of dentin matrix protein 1 (DMP1-C) 619:673 In this work, bone sialoprotein, osteopontin (OPN), dentin sialoprotein (DSP), dentin phosphoprotein (DPP), C-terminal fragment of dentin matrix protein 1 (DMP1-C), and proteoglycan versions of DSP (DSP-PG) and DMP1 (DMP1-PG) were tested individually to determine their roles in collagen fibrillogenesis and the prevention of denaturation. 28910556 1 5 gly glycoprotein 223:234 arg1 binding 205:211 small integrin binding 190:211 small integrin binding 190:211 Bone tissue is comprised of collagen, non-collagenous proteins, and hydroxyapatite and the SIBLING (small integrin binding, N-linked glycoprotein) family of proteins is the primary group of non-collagenous proteins. 28910556 1 5 gly glycoprotein 223:234 arg1 glycoprotein 223:234 N-linked glycoprotein 214:234 N-linked glycoprotein 214:234 Bone tissue is comprised of collagen, non-collagenous proteins, and hydroxyapatite and the SIBLING (small integrin binding, N-linked glycoprotein) family of proteins is the primary group of non-collagenous proteins. 28910556 1 6 theme proteins 247:254 arg1 family 237:242 the SIBLING (small integrin binding, N-linked glycoprotein) family 177:242 the SIBLING (small integrin binding, N-linked glycoprotein) family of proteins 177:254 Bone tissue is comprised of collagen, non-collagenous proteins, and hydroxyapatite and the SIBLING (small integrin binding, N-linked glycoprotein) family of proteins is the primary group of non-collagenous proteins. 28910556 1 6 theme proteins 247:254 arg1 group 271:275 the primary group 259:275 the primary group of non-collagenous proteins 259:303 Bone tissue is comprised of collagen, non-collagenous proteins, and hydroxyapatite and the SIBLING (small integrin binding, N-linked glycoprotein) family of proteins is the primary group of non-collagenous proteins. 28910556 1 6 theme proteins 247:254 arg1 proteins 296:303 non-collagenous proteins 280:303 non-collagenous proteins 280:303 Bone tissue is comprised of collagen, non-collagenous proteins, and hydroxyapatite and the SIBLING (small integrin binding, N-linked glycoprotein) family of proteins is the primary group of non-collagenous proteins. 28910556 5 7 dep DSP 1016:1018 arg1 the 1000:1002 the 1000:1002 the 1000:1002 In addition, the denaturation time was faster in the presence of DSP and OPN, indicating a negative impact. 28910556 5 7 dep DSP 1016:1018 arg1 presence 1004:1011 presence 1004:1011 presence 1004:1011 In addition, the denaturation time was faster in the presence of DSP and OPN, indicating a negative impact. 28910556 3 8 theme DMP1 722:725 arg1 versions 693:700 proteoglycan versions 680:700 proteoglycan versions of DSP (DSP-PG) and DMP1 (DMP1-PG) 680:735 In this work, bone sialoprotein, osteopontin (OPN), dentin sialoprotein (DSP), dentin phosphoprotein (DPP), C-terminal fragment of dentin matrix protein 1 (DMP1-C), and proteoglycan versions of DSP (DSP-PG) and DMP1 (DMP1-PG) were tested individually to determine their roles in collagen fibrillogenesis and the prevention of denaturation. 28910556 3 8 theme DMP1 722:725 arg1 phosphoprotein 597:610 dentin phosphoprotein 590:610 dentin phosphoprotein (DPP) 590:616 In this work, bone sialoprotein, osteopontin (OPN), dentin sialoprotein (DSP), dentin phosphoprotein (DPP), C-terminal fragment of dentin matrix protein 1 (DMP1-C), and proteoglycan versions of DSP (DSP-PG) and DMP1 (DMP1-PG) were tested individually to determine their roles in collagen fibrillogenesis and the prevention of denaturation. 28910556 3 8 theme DMP1 722:725 arg1 fragment 630:637 C-terminal fragment 619:637 C-terminal fragment of dentin matrix protein 1 (DMP1-C) 619:673 In this work, bone sialoprotein, osteopontin (OPN), dentin sialoprotein (DSP), dentin phosphoprotein (DPP), C-terminal fragment of dentin matrix protein 1 (DMP1-C), and proteoglycan versions of DSP (DSP-PG) and DMP1 (DMP1-PG) were tested individually to determine their roles in collagen fibrillogenesis and the prevention of denaturation. 28910556 3 8 theme DMP1 722:725 arg1 osteopontin 544:554 osteopontin 544:554 osteopontin (OPN) 544:560 In this work, bone sialoprotein, osteopontin (OPN), dentin sialoprotein (DSP), dentin phosphoprotein (DPP), C-terminal fragment of dentin matrix protein 1 (DMP1-C), and proteoglycan versions of DSP (DSP-PG) and DMP1 (DMP1-PG) were tested individually to determine their roles in collagen fibrillogenesis and the prevention of denaturation. 28910556 3 8 theme DMP1 722:725 arg1 sialoprotein 570:581 dentin sialoprotein 563:581 dentin sialoprotein (DSP) 563:587 In this work, bone sialoprotein, osteopontin (OPN), dentin sialoprotein (DSP), dentin phosphoprotein (DPP), C-terminal fragment of dentin matrix protein 1 (DMP1-C), and proteoglycan versions of DSP (DSP-PG) and DMP1 (DMP1-PG) were tested individually to determine their roles in collagen fibrillogenesis and the prevention of denaturation. 28910556 3 8 theme DMP1 722:725 arg1 sialoprotein 530:541 bone sialoprotein 525:541 bone sialoprotein 525:541 In this work, bone sialoprotein, osteopontin (OPN), dentin sialoprotein (DSP), dentin phosphoprotein (DPP), C-terminal fragment of dentin matrix protein 1 (DMP1-C), and proteoglycan versions of DSP (DSP-PG) and DMP1 (DMP1-PG) were tested individually to determine their roles in collagen fibrillogenesis and the prevention of denaturation. 28910556 3 8 theme DMP1 722:725 arg1 DPP 613:615 DPP 613:615 DPP 613:615 In this work, bone sialoprotein, osteopontin (OPN), dentin sialoprotein (DSP), dentin phosphoprotein (DPP), C-terminal fragment of dentin matrix protein 1 (DMP1-C), and proteoglycan versions of DSP (DSP-PG) and DMP1 (DMP1-PG) were tested individually to determine their roles in collagen fibrillogenesis and the prevention of denaturation. 28910556 3 8 theme DMP1 722:725 arg1 DSP 584:586 DSP 584:586 DSP 584:586 In this work, bone sialoprotein, osteopontin (OPN), dentin sialoprotein (DSP), dentin phosphoprotein (DPP), C-terminal fragment of dentin matrix protein 1 (DMP1-C), and proteoglycan versions of DSP (DSP-PG) and DMP1 (DMP1-PG) were tested individually to determine their roles in collagen fibrillogenesis and the prevention of denaturation. 28910556 3 8 theme DMP1 722:725 arg1 OPN 557:559 OPN 557:559 OPN 557:559 In this work, bone sialoprotein, osteopontin (OPN), dentin sialoprotein (DSP), dentin phosphoprotein (DPP), C-terminal fragment of dentin matrix protein 1 (DMP1-C), and proteoglycan versions of DSP (DSP-PG) and DMP1 (DMP1-PG) were tested individually to determine their roles in collagen fibrillogenesis and the prevention of denaturation. 28910556 10 9 theme implant 1615:1621 arg1 surface 1597:1603 the surface 1593:1603 the surface of a bone implant 1593:1621 It is believed that incorporating DMP1-C or DSP on the surface of a bone implant may improve the collagen interactions with the implant, thereby facilitating improved osteointegration. 28910556 10 10 with interactions 1648:1659 arg1 implant 1670:1676 the implant 1666:1676 the implant 1666:1676 It is believed that incorporating DMP1-C or DSP on the surface of a bone implant may improve the collagen interactions with the implant, thereby facilitating improved osteointegration. 28910556 2 11 theme surrounding 491:501 arg1 tissue 503:508 the surrounding tissue 487:508 the surrounding tissue 487:508 By replicating the native interactions between collagen and the SIBLING proteins at the interface of an implant, it is believed that a bone scaffold will more easily integrate with the surrounding tissue. 28910556 2 12 theme implant 410:416 arg1 interface 394:402 the interface 390:402 the interface of an implant 390:416 By replicating the native interactions between collagen and the SIBLING proteins at the interface of an implant, it is believed that a bone scaffold will more easily integrate with the surrounding tissue. 28910556 3 13 from roles 781:785 arg1 fibrillogenesis 799:813 collagen fibrillogenesis 790:813 collagen fibrillogenesis 790:813 In this work, bone sialoprotein, osteopontin (OPN), dentin sialoprotein (DSP), dentin phosphoprotein (DPP), C-terminal fragment of dentin matrix protein 1 (DMP1-C), and proteoglycan versions of DSP (DSP-PG) and DMP1 (DMP1-PG) were tested individually to determine their roles in collagen fibrillogenesis and the prevention of denaturation. 28910556 9 14 contain had 1470:1472 arg1 Calcium 1376:1382 Calcium 1376:1382 Calcium 1376:1382 Calcium had a similar effect on the proteoglycan variants in the fibrillogenesis process, but had no impact on the denaturation process in the presence of these two. 28910556 9 14 contain had 1470:1472 arg2 impact 1477:1482 no impact 1474:1482 no impact 1474:1482 Calcium had a similar effect on the proteoglycan variants in the fibrillogenesis process, but had no impact on the denaturation process in the presence of these two. 28910556 9 15 contain had 1384:1386 arg1 Calcium 1376:1382 Calcium 1376:1382 Calcium 1376:1382 Calcium had a similar effect on the proteoglycan variants in the fibrillogenesis process, but had no impact on the denaturation process in the presence of these two. 28910556 9 15 contain had 1384:1386 arg2 effect 1398:1403 a similar effect 1388:1403 a similar effect on the proteoglycan variants 1388:1432 Calcium had a similar effect on the proteoglycan variants in the fibrillogenesis process, but had no impact on the denaturation process in the presence of these two. 28910556 3 16 theme matrix 649:654 arg1 protein 656:662 dentin matrix protein 1 642:664 dentin matrix protein 1 (DMP1-C) 642:673 In this work, bone sialoprotein, osteopontin (OPN), dentin sialoprotein (DSP), dentin phosphoprotein (DPP), C-terminal fragment of dentin matrix protein 1 (DMP1-C), and proteoglycan versions of DSP (DSP-PG) and DMP1 (DMP1-PG) were tested individually to determine their roles in collagen fibrillogenesis and the prevention of denaturation. 28910556 3 16 theme matrix 649:654 arg1 DMP1-C 667:672 DMP1-C 667:672 DMP1-C 667:672 In this work, bone sialoprotein, osteopontin (OPN), dentin sialoprotein (DSP), dentin phosphoprotein (DPP), C-terminal fragment of dentin matrix protein 1 (DMP1-C), and proteoglycan versions of DSP (DSP-PG) and DMP1 (DMP1-PG) were tested individually to determine their roles in collagen fibrillogenesis and the prevention of denaturation. 28910556 4 17 contain had 931:933 arg1 SIBLINGs 922:929 other SIBLINGs 916:929 other SIBLINGs 916:929 It was shown that DSP and DPP slowed down fibrillogenesis, while other SIBLINGs had limited impact. 28910556 4 17 contain had 931:933 arg2 impact 943:948 limited impact 935:948 limited impact 935:948 It was shown that DSP and DPP slowed down fibrillogenesis, while other SIBLINGs had limited impact. 28910556 3 18 theme collagen 790:797 arg1 fibrillogenesis 799:813 collagen fibrillogenesis 790:813 collagen fibrillogenesis 790:813 In this work, bone sialoprotein, osteopontin (OPN), dentin sialoprotein (DSP), dentin phosphoprotein (DPP), C-terminal fragment of dentin matrix protein 1 (DMP1-C), and proteoglycan versions of DSP (DSP-PG) and DMP1 (DMP1-PG) were tested individually to determine their roles in collagen fibrillogenesis and the prevention of denaturation. 28910556 3 19 theme protein 656:662 arg1 versions 693:700 proteoglycan versions 680:700 proteoglycan versions of DSP (DSP-PG) and DMP1 (DMP1-PG) 680:735 In this work, bone sialoprotein, osteopontin (OPN), dentin sialoprotein (DSP), dentin phosphoprotein (DPP), C-terminal fragment of dentin matrix protein 1 (DMP1-C), and proteoglycan versions of DSP (DSP-PG) and DMP1 (DMP1-PG) were tested individually to determine their roles in collagen fibrillogenesis and the prevention of denaturation. 28910556 3 19 theme protein 656:662 arg1 phosphoprotein 597:610 dentin phosphoprotein 590:610 dentin phosphoprotein (DPP) 590:616 In this work, bone sialoprotein, osteopontin (OPN), dentin sialoprotein (DSP), dentin phosphoprotein (DPP), C-terminal fragment of dentin matrix protein 1 (DMP1-C), and proteoglycan versions of DSP (DSP-PG) and DMP1 (DMP1-PG) were tested individually to determine their roles in collagen fibrillogenesis and the prevention of denaturation. 28910556 3 19 theme protein 656:662 arg1 fragment 630:637 C-terminal fragment 619:637 C-terminal fragment of dentin matrix protein 1 (DMP1-C) 619:673 In this work, bone sialoprotein, osteopontin (OPN), dentin sialoprotein (DSP), dentin phosphoprotein (DPP), C-terminal fragment of dentin matrix protein 1 (DMP1-C), and proteoglycan versions of DSP (DSP-PG) and DMP1 (DMP1-PG) were tested individually to determine their roles in collagen fibrillogenesis and the prevention of denaturation. 28910556 3 19 theme protein 656:662 arg1 osteopontin 544:554 osteopontin 544:554 osteopontin (OPN) 544:560 In this work, bone sialoprotein, osteopontin (OPN), dentin sialoprotein (DSP), dentin phosphoprotein (DPP), C-terminal fragment of dentin matrix protein 1 (DMP1-C), and proteoglycan versions of DSP (DSP-PG) and DMP1 (DMP1-PG) were tested individually to determine their roles in collagen fibrillogenesis and the prevention of denaturation. 28910556 3 19 theme protein 656:662 arg1 sialoprotein 570:581 dentin sialoprotein 563:581 dentin sialoprotein (DSP) 563:587 In this work, bone sialoprotein, osteopontin (OPN), dentin sialoprotein (DSP), dentin phosphoprotein (DPP), C-terminal fragment of dentin matrix protein 1 (DMP1-C), and proteoglycan versions of DSP (DSP-PG) and DMP1 (DMP1-PG) were tested individually to determine their roles in collagen fibrillogenesis and the prevention of denaturation. 28910556 3 19 theme protein 656:662 arg1 sialoprotein 530:541 bone sialoprotein 525:541 bone sialoprotein 525:541 In this work, bone sialoprotein, osteopontin (OPN), dentin sialoprotein (DSP), dentin phosphoprotein (DPP), C-terminal fragment of dentin matrix protein 1 (DMP1-C), and proteoglycan versions of DSP (DSP-PG) and DMP1 (DMP1-PG) were tested individually to determine their roles in collagen fibrillogenesis and the prevention of denaturation. 28910556 3 19 theme protein 656:662 arg1 DPP 613:615 DPP 613:615 DPP 613:615 In this work, bone sialoprotein, osteopontin (OPN), dentin sialoprotein (DSP), dentin phosphoprotein (DPP), C-terminal fragment of dentin matrix protein 1 (DMP1-C), and proteoglycan versions of DSP (DSP-PG) and DMP1 (DMP1-PG) were tested individually to determine their roles in collagen fibrillogenesis and the prevention of denaturation. 28910556 3 19 theme protein 656:662 arg1 DSP 584:586 DSP 584:586 DSP 584:586 In this work, bone sialoprotein, osteopontin (OPN), dentin sialoprotein (DSP), dentin phosphoprotein (DPP), C-terminal fragment of dentin matrix protein 1 (DMP1-C), and proteoglycan versions of DSP (DSP-PG) and DMP1 (DMP1-PG) were tested individually to determine their roles in collagen fibrillogenesis and the prevention of denaturation. 28910556 3 19 theme protein 656:662 arg1 OPN 557:559 OPN 557:559 OPN 557:559 In this work, bone sialoprotein, osteopontin (OPN), dentin sialoprotein (DSP), dentin phosphoprotein (DPP), C-terminal fragment of dentin matrix protein 1 (DMP1-C), and proteoglycan versions of DSP (DSP-PG) and DMP1 (DMP1-PG) were tested individually to determine their roles in collagen fibrillogenesis and the prevention of denaturation. 28910556 9 20 theme denaturation 1491:1502 arg1 process 1504:1510 the denaturation process 1487:1510 the denaturation process in the presence of these two 1487:1539 Calcium had a similar effect on the proteoglycan variants in the fibrillogenesis process, but had no impact on the denaturation process in the presence of these two. 28910556 5 21 theme negative 1042:1049 arg1 impact 1051:1056 a negative impact 1040:1056 a negative impact 1040:1056 In addition, the denaturation time was faster in the presence of DSP and OPN, indicating a negative impact. 28910556 1 22 theme Bone 90:93 arg1 tissue 95:100 Bone tissue 90:100 Bone tissue 90:100 Bone tissue is comprised of collagen, non-collagenous proteins, and hydroxyapatite and the SIBLING (small integrin binding, N-linked glycoprotein) family of proteins is the primary group of non-collagenous proteins. 28910556 1 23 theme SIBLING 181:187 arg1 family 237:242 the SIBLING (small integrin binding, N-linked glycoprotein) family 177:242 the SIBLING (small integrin binding, N-linked glycoprotein) family of proteins 177:254 Bone tissue is comprised of collagen, non-collagenous proteins, and hydroxyapatite and the SIBLING (small integrin binding, N-linked glycoprotein) family of proteins is the primary group of non-collagenous proteins. 28910556 1 23 theme SIBLING 181:187 arg1 group 271:275 the primary group 259:275 the primary group of non-collagenous proteins 259:303 Bone tissue is comprised of collagen, non-collagenous proteins, and hydroxyapatite and the SIBLING (small integrin binding, N-linked glycoprotein) family of proteins is the primary group of non-collagenous proteins. 28910556 1 23 theme SIBLING 181:187 arg1 proteins 296:303 non-collagenous proteins 280:303 non-collagenous proteins 280:303 Bone tissue is comprised of collagen, non-collagenous proteins, and hydroxyapatite and the SIBLING (small integrin binding, N-linked glycoprotein) family of proteins is the primary group of non-collagenous proteins. 28910556 4 24 theme other 916:920 arg1 SIBLINGs 922:929 other SIBLINGs 916:929 other SIBLINGs 916:929 It was shown that DSP and DPP slowed down fibrillogenesis, while other SIBLINGs had limited impact. 28910556 1 25 theme primary 263:269 arg1 family 237:242 the SIBLING (small integrin binding, N-linked glycoprotein) family 177:242 the SIBLING (small integrin binding, N-linked glycoprotein) family of proteins 177:254 Bone tissue is comprised of collagen, non-collagenous proteins, and hydroxyapatite and the SIBLING (small integrin binding, N-linked glycoprotein) family of proteins is the primary group of non-collagenous proteins. 28910556 1 25 theme primary 263:269 arg1 group 271:275 the primary group 259:275 the primary group of non-collagenous proteins 259:303 Bone tissue is comprised of collagen, non-collagenous proteins, and hydroxyapatite and the SIBLING (small integrin binding, N-linked glycoprotein) family of proteins is the primary group of non-collagenous proteins. 28910556 1 25 theme primary 263:269 arg1 proteins 296:303 non-collagenous proteins 280:303 non-collagenous proteins 280:303 Bone tissue is comprised of collagen, non-collagenous proteins, and hydroxyapatite and the SIBLING (small integrin binding, N-linked glycoprotein) family of proteins is the primary group of non-collagenous proteins. 28910556 9 26 theme fibrillogenesis 1441:1455 arg1 process 1457:1463 the fibrillogenesis process 1437:1463 the fibrillogenesis process 1437:1463 Calcium had a similar effect on the proteoglycan variants in the fibrillogenesis process, but had no impact on the denaturation process in the presence of these two. 28910556 1 27 link N-linked 214:221 arg1 binding 205:211 small integrin binding 190:211 small integrin binding 190:211 Bone tissue is comprised of collagen, non-collagenous proteins, and hydroxyapatite and the SIBLING (small integrin binding, N-linked glycoprotein) family of proteins is the primary group of non-collagenous proteins. 28910556 1 27 link N-linked 214:221 arg1 glycoprotein 223:234 N-linked glycoprotein 214:234 N-linked glycoprotein 214:234 Bone tissue is comprised of collagen, non-collagenous proteins, and hydroxyapatite and the SIBLING (small integrin binding, N-linked glycoprotein) family of proteins is the primary group of non-collagenous proteins. 28910556 9 28 theme similar 1390:1396 arg1 effect 1398:1403 a similar effect 1388:1403 a similar effect on the proteoglycan variants 1388:1432 Calcium had a similar effect on the proteoglycan variants in the fibrillogenesis process, but had no impact on the denaturation process in the presence of these two. 28910556 3 29 theme denaturation 837:848 arg1 roles 781:785 their roles 775:785 their roles in collagen fibrillogenesis 775:813 In this work, bone sialoprotein, osteopontin (OPN), dentin sialoprotein (DSP), dentin phosphoprotein (DPP), C-terminal fragment of dentin matrix protein 1 (DMP1-C), and proteoglycan versions of DSP (DSP-PG) and DMP1 (DMP1-PG) were tested individually to determine their roles in collagen fibrillogenesis and the prevention of denaturation. 28910556 3 29 theme denaturation 837:848 arg1 prevention 823:832 the prevention 819:832 the prevention of denaturation 819:848 In this work, bone sialoprotein, osteopontin (OPN), dentin sialoprotein (DSP), dentin phosphoprotein (DPP), C-terminal fragment of dentin matrix protein 1 (DMP1-C), and proteoglycan versions of DSP (DSP-PG) and DMP1 (DMP1-PG) were tested individually to determine their roles in collagen fibrillogenesis and the prevention of denaturation. 28910556 4 30 theme limited 935:941 arg1 impact 943:948 limited impact 935:948 limited impact 935:948 It was shown that DSP and DPP slowed down fibrillogenesis, while other SIBLINGs had limited impact. 28910556 9 31 from process 1504:1510 arg1 presence 1519:1526 the presence 1515:1526 the presence of these two 1515:1539 Calcium had a similar effect on the proteoglycan variants in the fibrillogenesis process, but had no impact on the denaturation process in the presence of these two. 28910556 3 32 theme bone 525:528 arg1 sialoprotein 530:541 bone sialoprotein 525:541 bone sialoprotein 525:541 In this work, bone sialoprotein, osteopontin (OPN), dentin sialoprotein (DSP), dentin phosphoprotein (DPP), C-terminal fragment of dentin matrix protein 1 (DMP1-C), and proteoglycan versions of DSP (DSP-PG) and DMP1 (DMP1-PG) were tested individually to determine their roles in collagen fibrillogenesis and the prevention of denaturation. 28910556 3 33 from prevention 823:832 arg1 fibrillogenesis 799:813 collagen fibrillogenesis 790:813 collagen fibrillogenesis 790:813 In this work, bone sialoprotein, osteopontin (OPN), dentin sialoprotein (DSP), dentin phosphoprotein (DPP), C-terminal fragment of dentin matrix protein 1 (DMP1-C), and proteoglycan versions of DSP (DSP-PG) and DMP1 (DMP1-PG) were tested individually to determine their roles in collagen fibrillogenesis and the prevention of denaturation. 28910556 1 34 theme small 190:194 arg1 binding 205:211 small integrin binding 190:211 small integrin binding 190:211 Bone tissue is comprised of collagen, non-collagenous proteins, and hydroxyapatite and the SIBLING (small integrin binding, N-linked glycoprotein) family of proteins is the primary group of non-collagenous proteins. 28910556 1 34 theme small 190:194 arg1 glycoprotein 223:234 N-linked glycoprotein 214:234 N-linked glycoprotein 214:234 Bone tissue is comprised of collagen, non-collagenous proteins, and hydroxyapatite and the SIBLING (small integrin binding, N-linked glycoprotein) family of proteins is the primary group of non-collagenous proteins. 28910556 3 35 theme dentin 590:595 arg1 DPP 613:615 DPP 613:615 DPP 613:615 In this work, bone sialoprotein, osteopontin (OPN), dentin sialoprotein (DSP), dentin phosphoprotein (DPP), C-terminal fragment of dentin matrix protein 1 (DMP1-C), and proteoglycan versions of DSP (DSP-PG) and DMP1 (DMP1-PG) were tested individually to determine their roles in collagen fibrillogenesis and the prevention of denaturation. 28910556 3 35 theme dentin 590:595 arg1 phosphoprotein 597:610 dentin phosphoprotein 590:610 dentin phosphoprotein (DPP) 590:616 In this work, bone sialoprotein, osteopontin (OPN), dentin sialoprotein (DSP), dentin phosphoprotein (DPP), C-terminal fragment of dentin matrix protein 1 (DMP1-C), and proteoglycan versions of DSP (DSP-PG) and DMP1 (DMP1-PG) were tested individually to determine their roles in collagen fibrillogenesis and the prevention of denaturation. 28910556 1 36 theme integrin 196:203 arg1 binding 205:211 small integrin binding 190:211 small integrin binding 190:211 Bone tissue is comprised of collagen, non-collagenous proteins, and hydroxyapatite and the SIBLING (small integrin binding, N-linked glycoprotein) family of proteins is the primary group of non-collagenous proteins. 28910556 1 36 theme integrin 196:203 arg1 glycoprotein 223:234 N-linked glycoprotein 214:234 N-linked glycoprotein 214:234 Bone tissue is comprised of collagen, non-collagenous proteins, and hydroxyapatite and the SIBLING (small integrin binding, N-linked glycoprotein) family of proteins is the primary group of non-collagenous proteins. 28910556 0 37 theme proteins 33:40 arg1 influence 12:20 the influence 8:20 the influence of SIBLING proteins on collagen-I fibrillogenesis and denaturation 8:87 Probing the influence of SIBLING proteins on collagen-I fibrillogenesis and denaturation. 28910556 1 38 theme non-collagenous 280:294 arg1 proteins 296:303 non-collagenous proteins 280:303 non-collagenous proteins 280:303 Bone tissue is comprised of collagen, non-collagenous proteins, and hydroxyapatite and the SIBLING (small integrin binding, N-linked glycoprotein) family of proteins is the primary group of non-collagenous proteins. 28910556 1 39 dep SIBLING 181:187 arg1 binding 205:211 small integrin binding 190:211 small integrin binding 190:211 Bone tissue is comprised of collagen, non-collagenous proteins, and hydroxyapatite and the SIBLING (small integrin binding, N-linked glycoprotein) family of proteins is the primary group of non-collagenous proteins. 28910556 1 39 dep SIBLING 181:187 arg1 glycoprotein 223:234 N-linked glycoprotein 214:234 N-linked glycoprotein 214:234 Bone tissue is comprised of collagen, non-collagenous proteins, and hydroxyapatite and the SIBLING (small integrin binding, N-linked glycoprotein) family of proteins is the primary group of non-collagenous proteins. 28910556 0 40 theme SIBLING 25:31 arg1 proteins 33:40 SIBLING proteins 25:40 SIBLING proteins 25:40 Probing the influence of SIBLING proteins on collagen-I fibrillogenesis and denaturation. 28910556 1 41 theme proteins 296:303 arg1 family 237:242 the SIBLING (small integrin binding, N-linked glycoprotein) family 177:242 the SIBLING (small integrin binding, N-linked glycoprotein) family of proteins 177:254 Bone tissue is comprised of collagen, non-collagenous proteins, and hydroxyapatite and the SIBLING (small integrin binding, N-linked glycoprotein) family of proteins is the primary group of non-collagenous proteins. 28910556 1 41 theme proteins 296:303 arg1 group 271:275 the primary group 259:275 the primary group of non-collagenous proteins 259:303 Bone tissue is comprised of collagen, non-collagenous proteins, and hydroxyapatite and the SIBLING (small integrin binding, N-linked glycoprotein) family of proteins is the primary group of non-collagenous proteins. 28910556 1 41 theme proteins 296:303 arg1 proteins 296:303 non-collagenous proteins 280:303 non-collagenous proteins 280:303 Bone tissue is comprised of collagen, non-collagenous proteins, and hydroxyapatite and the SIBLING (small integrin binding, N-linked glycoprotein) family of proteins is the primary group of non-collagenous proteins. 28910556 5 42 theme denaturation 968:979 arg1 faster 990:995 faster 990:995 faster 990:995 In addition, the denaturation time was faster in the presence of DSP and OPN, indicating a negative impact. 28910556 5 42 theme denaturation 968:979 arg1 time 981:984 the denaturation time 964:984 the denaturation time 964:984 In addition, the denaturation time was faster in the presence of DSP and OPN, indicating a negative impact. 28910556 9 43 theme proteoglycan 1412:1423 arg1 variants 1425:1432 the proteoglycan variants 1408:1432 the proteoglycan variants 1408:1432 Calcium had a similar effect on the proteoglycan variants in the fibrillogenesis process, but had no impact on the denaturation process in the presence of these two. 28910556 2 44 theme bone 441:444 arg1 scaffold 446:453 a bone scaffold 439:453 a bone scaffold 439:453 By replicating the native interactions between collagen and the SIBLING proteins at the interface of an implant, it is believed that a bone scaffold will more easily integrate with the surrounding tissue. 28910556 3 45 theme DSP 705:707 arg1 versions 693:700 proteoglycan versions 680:700 proteoglycan versions of DSP (DSP-PG) and DMP1 (DMP1-PG) 680:735 In this work, bone sialoprotein, osteopontin (OPN), dentin sialoprotein (DSP), dentin phosphoprotein (DPP), C-terminal fragment of dentin matrix protein 1 (DMP1-C), and proteoglycan versions of DSP (DSP-PG) and DMP1 (DMP1-PG) were tested individually to determine their roles in collagen fibrillogenesis and the prevention of denaturation. 28910556 3 45 theme DSP 705:707 arg1 phosphoprotein 597:610 dentin phosphoprotein 590:610 dentin phosphoprotein (DPP) 590:616 In this work, bone sialoprotein, osteopontin (OPN), dentin sialoprotein (DSP), dentin phosphoprotein (DPP), C-terminal fragment of dentin matrix protein 1 (DMP1-C), and proteoglycan versions of DSP (DSP-PG) and DMP1 (DMP1-PG) were tested individually to determine their roles in collagen fibrillogenesis and the prevention of denaturation. 28910556 3 45 theme DSP 705:707 arg1 fragment 630:637 C-terminal fragment 619:637 C-terminal fragment of dentin matrix protein 1 (DMP1-C) 619:673 In this work, bone sialoprotein, osteopontin (OPN), dentin sialoprotein (DSP), dentin phosphoprotein (DPP), C-terminal fragment of dentin matrix protein 1 (DMP1-C), and proteoglycan versions of DSP (DSP-PG) and DMP1 (DMP1-PG) were tested individually to determine their roles in collagen fibrillogenesis and the prevention of denaturation. 28910556 3 45 theme DSP 705:707 arg1 osteopontin 544:554 osteopontin 544:554 osteopontin (OPN) 544:560 In this work, bone sialoprotein, osteopontin (OPN), dentin sialoprotein (DSP), dentin phosphoprotein (DPP), C-terminal fragment of dentin matrix protein 1 (DMP1-C), and proteoglycan versions of DSP (DSP-PG) and DMP1 (DMP1-PG) were tested individually to determine their roles in collagen fibrillogenesis and the prevention of denaturation. 28910556 3 45 theme DSP 705:707 arg1 sialoprotein 570:581 dentin sialoprotein 563:581 dentin sialoprotein (DSP) 563:587 In this work, bone sialoprotein, osteopontin (OPN), dentin sialoprotein (DSP), dentin phosphoprotein (DPP), C-terminal fragment of dentin matrix protein 1 (DMP1-C), and proteoglycan versions of DSP (DSP-PG) and DMP1 (DMP1-PG) were tested individually to determine their roles in collagen fibrillogenesis and the prevention of denaturation. 28910556 3 45 theme DSP 705:707 arg1 sialoprotein 530:541 bone sialoprotein 525:541 bone sialoprotein 525:541 In this work, bone sialoprotein, osteopontin (OPN), dentin sialoprotein (DSP), dentin phosphoprotein (DPP), C-terminal fragment of dentin matrix protein 1 (DMP1-C), and proteoglycan versions of DSP (DSP-PG) and DMP1 (DMP1-PG) were tested individually to determine their roles in collagen fibrillogenesis and the prevention of denaturation. 28910556 3 45 theme DSP 705:707 arg1 DPP 613:615 DPP 613:615 DPP 613:615 In this work, bone sialoprotein, osteopontin (OPN), dentin sialoprotein (DSP), dentin phosphoprotein (DPP), C-terminal fragment of dentin matrix protein 1 (DMP1-C), and proteoglycan versions of DSP (DSP-PG) and DMP1 (DMP1-PG) were tested individually to determine their roles in collagen fibrillogenesis and the prevention of denaturation. 28910556 3 45 theme DSP 705:707 arg1 DSP 584:586 DSP 584:586 DSP 584:586 In this work, bone sialoprotein, osteopontin (OPN), dentin sialoprotein (DSP), dentin phosphoprotein (DPP), C-terminal fragment of dentin matrix protein 1 (DMP1-C), and proteoglycan versions of DSP (DSP-PG) and DMP1 (DMP1-PG) were tested individually to determine their roles in collagen fibrillogenesis and the prevention of denaturation. 28910556 3 45 theme DSP 705:707 arg1 OPN 557:559 OPN 557:559 OPN 557:559 In this work, bone sialoprotein, osteopontin (OPN), dentin sialoprotein (DSP), dentin phosphoprotein (DPP), C-terminal fragment of dentin matrix protein 1 (DMP1-C), and proteoglycan versions of DSP (DSP-PG) and DMP1 (DMP1-PG) were tested individually to determine their roles in collagen fibrillogenesis and the prevention of denaturation. 28910556 8 46 theme most 1298:1301 arg1 cases 1303:1307 most cases 1298:1307 most cases 1298:1307 Calcium also sped up the denaturation in most cases, with the exception of DMP1-C and DSP where the opposite was seen. 28910556 7 47 theme negative 1217:1224 arg1 impact 1226:1231 a negative impact 1215:1231 a negative impact 1215:1231 The presence of calcium ions sped up fibrillogenesis in all scenarios tested, but it had a negative impact by reducing the extent. 28910556 7 48 theme calcium 1142:1148 arg1 ions 1150:1153 calcium ions 1142:1153 calcium ions 1142:1153 The presence of calcium ions sped up fibrillogenesis in all scenarios tested, but it had a negative impact by reducing the extent. 28910556 3 49 theme proteoglycan 680:691 arg1 versions 693:700 proteoglycan versions 680:700 proteoglycan versions of DSP (DSP-PG) and DMP1 (DMP1-PG) 680:735 In this work, bone sialoprotein, osteopontin (OPN), dentin sialoprotein (DSP), dentin phosphoprotein (DPP), C-terminal fragment of dentin matrix protein 1 (DMP1-C), and proteoglycan versions of DSP (DSP-PG) and DMP1 (DMP1-PG) were tested individually to determine their roles in collagen fibrillogenesis and the prevention of denaturation. 28910556 9 50 theme two 1537:1539 arg1 presence 1519:1526 the presence 1515:1526 the presence of these two 1515:1539 Calcium had a similar effect on the proteoglycan variants in the fibrillogenesis process, but had no impact on the denaturation process in the presence of these two. 28910556 7 51 theme ions 1150:1153 arg1 presence 1130:1137 The presence 1126:1137 The presence of calcium ions 1126:1153 The presence of calcium ions sped up fibrillogenesis in all scenarios tested, but it had a negative impact by reducing the extent. 28910556 9 52 from effect 1398:1403 arg1 variants 1425:1432 the proteoglycan variants 1408:1432 the proteoglycan variants 1408:1432 Calcium had a similar effect on the proteoglycan variants in the fibrillogenesis process, but had no impact on the denaturation process in the presence of these two. 28910556 6 53 theme ions 1079:1082 arg1 role 1063:1066 The role 1059:1066 The role of calcium ions in these processes 1059:1101 The role of calcium ions in these processes was also investigated. 28910556 2 54 theme native 325:330 arg1 interactions 332:343 the native interactions 321:343 the native interactions between collagen and the SIBLING proteins 321:385 By replicating the native interactions between collagen and the SIBLING proteins at the interface of an implant, it is believed that a bone scaffold will more easily integrate with the surrounding tissue. 28910556 1 55 theme N-linked 214:221 arg1 binding 205:211 small integrin binding 190:211 small integrin binding 190:211 Bone tissue is comprised of collagen, non-collagenous proteins, and hydroxyapatite and the SIBLING (small integrin binding, N-linked glycoprotein) family of proteins is the primary group of non-collagenous proteins. 28910556 1 55 theme N-linked 214:221 arg1 glycoprotein 223:234 N-linked glycoprotein 214:234 N-linked glycoprotein 214:234 Bone tissue is comprised of collagen, non-collagenous proteins, and hydroxyapatite and the SIBLING (small integrin binding, N-linked glycoprotein) family of proteins is the primary group of non-collagenous proteins. 28910556 6 56 theme calcium 1071:1077 arg1 ions 1079:1082 calcium ions 1071:1082 calcium ions 1071:1082 The role of calcium ions in these processes was also investigated. 28910556 1 57 theme non-collagenous 128:142 arg1 proteins 144:151 non-collagenous proteins 128:151 non-collagenous proteins 128:151 Bone tissue is comprised of collagen, non-collagenous proteins, and hydroxyapatite and the SIBLING (small integrin binding, N-linked glycoprotein) family of proteins is the primary group of non-collagenous proteins. 28910556 8 58 theme DSP 1343:1345 arg1 exception 1319:1327 the exception 1315:1327 the exception of DMP1-C and DSP where the opposite was seen 1315:1373 Calcium also sped up the denaturation in most cases, with the exception of DMP1-C and DSP where the opposite was seen. 28910556 10 59 theme collagen 1639:1646 arg1 interactions 1648:1659 the collagen interactions 1635:1659 the collagen interactions with the implant 1635:1676 It is believed that incorporating DMP1-C or DSP on the surface of a bone implant may improve the collagen interactions with the implant, thereby facilitating improved osteointegration. 28910556 3 60 theme dentin 563:568 arg1 sialoprotein 570:581 dentin sialoprotein 563:581 dentin sialoprotein (DSP) 563:587 In this work, bone sialoprotein, osteopontin (OPN), dentin sialoprotein (DSP), dentin phosphoprotein (DPP), C-terminal fragment of dentin matrix protein 1 (DMP1-C), and proteoglycan versions of DSP (DSP-PG) and DMP1 (DMP1-PG) were tested individually to determine their roles in collagen fibrillogenesis and the prevention of denaturation. 28910556 3 60 theme dentin 563:568 arg1 DSP 584:586 DSP 584:586 DSP 584:586 In this work, bone sialoprotein, osteopontin (OPN), dentin sialoprotein (DSP), dentin phosphoprotein (DPP), C-terminal fragment of dentin matrix protein 1 (DMP1-C), and proteoglycan versions of DSP (DSP-PG) and DMP1 (DMP1-PG) were tested individually to determine their roles in collagen fibrillogenesis and the prevention of denaturation. 28910556 2 61 theme SIBLING 370:376 arg1 proteins 378:385 the SIBLING proteins 366:385 the SIBLING proteins 366:385 By replicating the native interactions between collagen and the SIBLING proteins at the interface of an implant, it is believed that a bone scaffold will more easily integrate with the surrounding tissue. 28910556 0 62 theme collagen-I 45:54 arg1 fibrillogenesis 56:70 collagen-I fibrillogenesis 45:70 collagen-I fibrillogenesis 45:70 Probing the influence of SIBLING proteins on collagen-I fibrillogenesis and denaturation. 28910556 8 63 theme DMP1-C 1332:1337 arg1 exception 1319:1327 the exception 1315:1327 the exception of DMP1-C and DSP where the opposite was seen 1315:1373 Calcium also sped up the denaturation in most cases, with the exception of DMP1-C and DSP where the opposite was seen. 28910556 10 64 theme bone 1610:1613 arg1 implant 1615:1621 a bone implant 1608:1621 a bone implant 1608:1621 It is believed that incorporating DMP1-C or DSP on the surface of a bone implant may improve the collagen interactions with the implant, thereby facilitating improved osteointegration. 28910556 7 65 contain had 1211:1213 arg2 impact 1226:1231 a negative impact 1215:1231 a negative impact 1215:1231 The presence of calcium ions sped up fibrillogenesis in all scenarios tested, but it had a negative impact by reducing the extent. 28910556 7 65 contain had 1211:1213 arg1 it 1208:1209 it 1208:1209 it 1208:1209 The presence of calcium ions sped up fibrillogenesis in all scenarios tested, but it had a negative impact by reducing the extent. 28747311 8 0 with form 1205:1208 arg1 mass 1227:1230 an observed mass 1215:1230 an observed mass of 33,510 Da (matching oxidized form) 1215:1268 The expressed protein, purified by nickel affinity, ion exchange, and size exclusion chromatography to >90% purity, was present in monomeric form with an observed mass of 33,510 Da (matching oxidized form). 28747311 9 1 theme predicted 1344:1352 arg1 bonds 1364:1368 predicted disulfide bonds 1344:1368 predicted disulfide bonds 1344:1368 Peptide mapping and disulfide analysis confirmed the proper formation of predicted disulfide bonds. 28747311 8 2 theme ion 1116:1118 arg1 exchange 1120:1127 ion exchange 1116:1127 ion exchange 1116:1127 The expressed protein, purified by nickel affinity, ion exchange, and size exclusion chromatography to >90% purity, was present in monomeric form with an observed mass of 33,510 Da (matching oxidized form). 28747311 7 3 theme N-linked 1040:1047 arg1 glycosylation 1049:1061 potential N-linked glycosylation 1030:1061 potential N-linked glycosylation 1030:1061 Since the native host lacks glycosylation machinery, a single N585Q mutation was made to eliminate potential N-linked glycosylation. 28747311 2 4 theme surface 310:316 arg1 protein 318:324 a gametocyte surface protein 297:324 a gametocyte surface protein involved in gamete function 297:352 Pfs230, a gametocyte surface protein involved in gamete function, has long been a promising candidate. 28747311 2 4 theme surface 310:316 arg1 Pfs230 289:294 Pfs230 289:294 Pfs230 289:294 Pfs230, a gametocyte surface protein involved in gamete function, has long been a promising candidate. 28747311 6 5 theme affinity 884:891 arg1 tag 893:895 a polyhistidine affinity tag 868:895 a polyhistidine affinity tag 868:895 Pfs230C1 (amino acids 443 to 731) with a polyhistidine affinity tag was expressed in Super Sf9 cells. 28747311 12 6 theme expression 1875:1884 arg1 system 1886:1891 the scalable baculovirus expression system 1850:1891 the scalable baculovirus expression system 1850:1891 Our results also support the continued use of the scalable baculovirus expression system for the generation of complex Plasmodium proteins. 28747311 6 7 theme amino 839:843 arg1 Pfs230C1 829:836 Pfs230C1 829:836 Pfs230C1 (amino acids 443 to 731) with a polyhistidine affinity tag 829:895 Pfs230C1 (amino acids 443 to 731) with a polyhistidine affinity tag was expressed in Super Sf9 cells. 28747311 6 7 theme amino 839:843 arg1 acids 845:849 amino acids 443 to 731 839:860 amino acids 443 to 731 839:860 Pfs230C1 (amino acids 443 to 731) with a polyhistidine affinity tag was expressed in Super Sf9 cells. 28747311 8 8 theme size 1134:1137 arg1 chromatography 1149:1162 size exclusion chromatography 1134:1162 size exclusion chromatography 1134:1162 The expressed protein, purified by nickel affinity, ion exchange, and size exclusion chromatography to >90% purity, was present in monomeric form with an observed mass of 33,510 Da (matching oxidized form). 28747311 6 9 theme Super 914:918 arg1 cells 924:928 Super Sf9 cells 914:928 Super Sf9 cells 914:928 Pfs230C1 (amino acids 443 to 731) with a polyhistidine affinity tag was expressed in Super Sf9 cells. 28747311 3 10 with size 409:412 arg1 multitude 499:507 a multitude 497:507 a multitude of disulfide bonds 497:526 Due to the large size (3,135 amino acids), complex domains, and repeating 6-cysteine (6-Cys) motifs with a multitude of disulfide bonds, the feasibility of expression of a full-length protein has been difficult. 28747311 10 11 theme functional 1497:1506 arg1 activity 1508:1515 functional activity 1497:1515 functional activity 1497:1515 Antibodies, generated against Pfs230C1 in mice, bound to the gametocyte in an immunofluorescence assay (IFA) and demonstrated functional activity in both the standard membrane feeding assay (SMFA) and the exflagellation assay (EXA). 28747311 11 12 theme continued 1688:1696 arg1 advancement 1698:1708 the continued advancement 1684:1708 the continued advancement of an N-terminal Pfs230 antigen (Pfs230C1) 1684:1751 The biochemical, biophysical, and immunological results reported herein support the continued advancement of an N-terminal Pfs230 antigen (Pfs230C1) as a component of a transmission-blocking vaccine. 28747311 11 12 theme continued 1688:1696 arg1 component 1758:1766 a component 1756:1766 a component of a transmission-blocking vaccine 1756:1801 The biochemical, biophysical, and immunological results reported herein support the continued advancement of an N-terminal Pfs230 antigen (Pfs230C1) as a component of a transmission-blocking vaccine. 28747311 3 13 theme expression 548:557 arg1 feasibility 533:543 the feasibility 529:543 the feasibility of expression of a full-length protein 529:582 Due to the large size (3,135 amino acids), complex domains, and repeating 6-cysteine (6-Cys) motifs with a multitude of disulfide bonds, the feasibility of expression of a full-length protein has been difficult. 28747311 3 13 theme expression 548:557 arg1 difficult 593:601 difficult 593:601 difficult 593:601 Due to the large size (3,135 amino acids), complex domains, and repeating 6-cysteine (6-Cys) motifs with a multitude of disulfide bonds, the feasibility of expression of a full-length protein has been difficult. 28747311 5 14 theme Pfs230 810:815 arg1 Pfs230 810:815 Pfs230 810:815 Pfs230 (Pfs230C1) 810:826 Here we utilized a heterologous expression system, baculovirus, to produce an N-terminal domain of Pfs230 (Pfs230C1). 28747311 5 14 theme Pfs230 810:815 arg1 domain 800:805 an N-terminal domain 786:805 an N-terminal domain of Pfs230 (Pfs230C1) 786:826 Here we utilized a heterologous expression system, baculovirus, to produce an N-terminal domain of Pfs230 (Pfs230C1). 28747311 3 15 theme complex 435:441 arg1 domains 443:449 complex domains 435:449 complex domains 435:449 Due to the large size (3,135 amino acids), complex domains, and repeating 6-cysteine (6-Cys) motifs with a multitude of disulfide bonds, the feasibility of expression of a full-length protein has been difficult. 28747311 10 16 theme membrane 1538:1545 arg1 SMFA 1562:1565 SMFA 1562:1565 SMFA 1562:1565 Antibodies, generated against Pfs230C1 in mice, bound to the gametocyte in an immunofluorescence assay (IFA) and demonstrated functional activity in both the standard membrane feeding assay (SMFA) and the exflagellation assay (EXA). 28747311 10 16 theme membrane 1538:1545 arg1 assay 1555:1559 the standard membrane feeding assay 1525:1559 the standard membrane feeding assay (SMFA) 1525:1566 Antibodies, generated against Pfs230C1 in mice, bound to the gametocyte in an immunofluorescence assay (IFA) and demonstrated functional activity in both the standard membrane feeding assay (SMFA) and the exflagellation assay (EXA). 28747311 11 17 theme antigen 1734:1740 arg1 advancement 1698:1708 the continued advancement 1684:1708 the continued advancement of an N-terminal Pfs230 antigen (Pfs230C1) 1684:1751 The biochemical, biophysical, and immunological results reported herein support the continued advancement of an N-terminal Pfs230 antigen (Pfs230C1) as a component of a transmission-blocking vaccine. 28747311 11 17 theme antigen 1734:1740 arg1 component 1758:1766 a component 1756:1766 a component of a transmission-blocking vaccine 1756:1801 The biochemical, biophysical, and immunological results reported herein support the continued advancement of an N-terminal Pfs230 antigen (Pfs230C1) as a component of a transmission-blocking vaccine. 28747311 8 18 theme >90 1167:1169 arg1 % 1170:1170 % 1170:1170 % 1170:1170 The expressed protein, purified by nickel affinity, ion exchange, and size exclusion chromatography to >90% purity, was present in monomeric form with an observed mass of 33,510 Da (matching oxidized form). 28747311 1 19 from humans 267:272 arg1 transmission 249:260 parasite transmission 240:260 parasite transmission from humans to mosquitoes 240:286 Transmission-blocking vaccines have the potential to accelerate malaria parasite elimination by inducing antibodies that block parasite transmission from humans to mosquitoes. 28747311 11 20 theme N-terminal 1716:1725 arg1 Pfs230C1 1743:1750 Pfs230C1 1743:1750 Pfs230C1 1743:1750 The biochemical, biophysical, and immunological results reported herein support the continued advancement of an N-terminal Pfs230 antigen (Pfs230C1) as a component of a transmission-blocking vaccine. 28747311 11 20 theme N-terminal 1716:1725 arg1 antigen 1734:1740 an N-terminal Pfs230 antigen 1713:1740 an N-terminal Pfs230 antigen (Pfs230C1) 1713:1751 The biochemical, biophysical, and immunological results reported herein support the continued advancement of an N-terminal Pfs230 antigen (Pfs230C1) as a component of a transmission-blocking vaccine. 28747311 7 21 theme single 986:991 arg1 mutation 999:1006 a single N585Q mutation 984:1006 a single N585Q mutation 984:1006 Since the native host lacks glycosylation machinery, a single N585Q mutation was made to eliminate potential N-linked glycosylation. 28747311 3 22 theme protein 576:582 arg1 expression 548:557 expression 548:557 expression of a full-length protein 548:582 Due to the large size (3,135 amino acids), complex domains, and repeating 6-cysteine (6-Cys) motifs with a multitude of disulfide bonds, the feasibility of expression of a full-length protein has been difficult. 28747311 7 23 theme native 941:946 arg1 host 948:951 the native host 937:951 the native host 937:951 Since the native host lacks glycosylation machinery, a single N585Q mutation was made to eliminate potential N-linked glycosylation. 28747311 6 24 theme polyhistidine 870:882 arg1 tag 893:895 a polyhistidine affinity tag 868:895 a polyhistidine affinity tag 868:895 Pfs230C1 (amino acids 443 to 731) with a polyhistidine affinity tag was expressed in Super Sf9 cells. 28747311 11 25 theme immunological 1638:1650 arg1 results 1652:1658 The biochemical, biophysical, and immunological results 1604:1658 The biochemical, biophysical, and immunological results reported herein 1604:1674 The biochemical, biophysical, and immunological results reported herein support the continued advancement of an N-terminal Pfs230 antigen (Pfs230C1) as a component of a transmission-blocking vaccine. 28747311 8 26 from form 1205:1208 arg1 protein 1078:1084 The expressed protein 1064:1084 The expressed protein 1064:1084 The expressed protein, purified by nickel affinity, ion exchange, and size exclusion chromatography to >90% purity, was present in monomeric form with an observed mass of 33,510 Da (matching oxidized form). 28747311 8 26 from form 1205:1208 arg1 present 1184:1190 present 1184:1190 present 1184:1190 The expressed protein, purified by nickel affinity, ion exchange, and size exclusion chromatography to >90% purity, was present in monomeric form with an observed mass of 33,510 Da (matching oxidized form). 28747311 5 27 theme heterologous 730:741 arg1 baculovirus 762:772 baculovirus 762:772 baculovirus 762:772 Here we utilized a heterologous expression system, baculovirus, to produce an N-terminal domain of Pfs230 (Pfs230C1). 28747311 5 27 theme heterologous 730:741 arg1 system 754:759 a heterologous expression system 728:759 a heterologous expression system 728:759 Here we utilized a heterologous expression system, baculovirus, to produce an N-terminal domain of Pfs230 (Pfs230C1). 28747311 1 28 theme malaria 177:183 arg1 elimination 194:204 malaria parasite elimination 177:204 malaria parasite elimination 177:204 Transmission-blocking vaccines have the potential to accelerate malaria parasite elimination by inducing antibodies that block parasite transmission from humans to mosquitoes. 28747311 4 29 theme domains 670:676 arg1 generation 649:658 the generation 645:658 the generation of single domains, including N-terminal fragments 645:708 A priority focus, therefore, has been on the generation of single domains, including N-terminal fragments. 28747311 0 30 theme Transmission-Blocking 72:92 arg1 Candidate 102:110 a Biological Active Transmission-Blocking Vaccine Candidate 52:110 a Biological Active Transmission-Blocking Vaccine Candidate 52:110 N-Terminal Pfs230 Domain Produced in Baculovirus as a Biological Active Transmission-Blocking Vaccine Candidate. 28747311 8 31 theme oxidized 1255:1262 arg1 form 1264:1267 oxidized form 1255:1267 oxidized form 1255:1267 The expressed protein, purified by nickel affinity, ion exchange, and size exclusion chromatography to >90% purity, was present in monomeric form with an observed mass of 33,510 Da (matching oxidized form). 28747311 8 32 theme observed 1218:1225 arg1 mass 1227:1230 an observed mass 1215:1230 an observed mass of 33,510 Da (matching oxidized form) 1215:1268 The expressed protein, purified by nickel affinity, ion exchange, and size exclusion chromatography to >90% purity, was present in monomeric form with an observed mass of 33,510 Da (matching oxidized form). 28747311 12 33 theme complex 1915:1921 arg1 proteins 1934:1941 complex Plasmodium proteins 1915:1941 complex Plasmodium proteins 1915:1941 Our results also support the continued use of the scalable baculovirus expression system for the generation of complex Plasmodium proteins. 28747311 11 34 theme vaccine 1795:1801 arg1 advancement 1698:1708 the continued advancement 1684:1708 the continued advancement of an N-terminal Pfs230 antigen (Pfs230C1) 1684:1751 The biochemical, biophysical, and immunological results reported herein support the continued advancement of an N-terminal Pfs230 antigen (Pfs230C1) as a component of a transmission-blocking vaccine. 28747311 11 34 theme vaccine 1795:1801 arg1 component 1758:1766 a component 1756:1766 a component of a transmission-blocking vaccine 1756:1801 The biochemical, biophysical, and immunological results reported herein support the continued advancement of an N-terminal Pfs230 antigen (Pfs230C1) as a component of a transmission-blocking vaccine. 28747311 0 35 theme N-Terminal 0:9 arg1 Domain 18:23 N-Terminal Pfs230 Domain 0:23 N-Terminal Pfs230 Domain 0:23 N-Terminal Pfs230 Domain Produced in Baculovirus as a Biological Active Transmission-Blocking Vaccine Candidate. 28747311 8 36 attach present 1184:1190 arg2 protein 1078:1084 The expressed protein 1064:1084 The expressed protein 1064:1084 The expressed protein, purified by nickel affinity, ion exchange, and size exclusion chromatography to >90% purity, was present in monomeric form with an observed mass of 33,510 Da (matching oxidized form). 28747311 8 36 attach present 1184:1190 arg2 present 1184:1190 present 1184:1190 present 1184:1190 The expressed protein, purified by nickel affinity, ion exchange, and size exclusion chromatography to >90% purity, was present in monomeric form with an observed mass of 33,510 Da (matching oxidized form). 28747311 8 36 attach present 1184:1190 arg1 form 1205:1208 monomeric form 1195:1208 monomeric form with an observed mass of 33,510 Da (matching oxidized form) 1195:1268 The expressed protein, purified by nickel affinity, ion exchange, and size exclusion chromatography to >90% purity, was present in monomeric form with an observed mass of 33,510 Da (matching oxidized form). 28747311 6 37 with Pfs230C1 829:836 arg1 tag 893:895 a polyhistidine affinity tag 868:895 a polyhistidine affinity tag 868:895 Pfs230C1 (amino acids 443 to 731) with a polyhistidine affinity tag was expressed in Super Sf9 cells. 28747311 3 38 theme 6-cysteine 466:475 arg1 motifs 485:490 repeating 6-cysteine (6-Cys) motifs 456:490 repeating 6-cysteine (6-Cys) motifs with a multitude of disulfide bonds 456:526 Due to the large size (3,135 amino acids), complex domains, and repeating 6-cysteine (6-Cys) motifs with a multitude of disulfide bonds, the feasibility of expression of a full-length protein has been difficult. 28747311 0 39 theme Biological 54:63 arg1 Candidate 102:110 a Biological Active Transmission-Blocking Vaccine Candidate 52:110 a Biological Active Transmission-Blocking Vaccine Candidate 52:110 N-Terminal Pfs230 Domain Produced in Baculovirus as a Biological Active Transmission-Blocking Vaccine Candidate. 28747311 2 40 theme promising 371:379 arg1 Pfs230 289:294 Pfs230 289:294 Pfs230 289:294 Pfs230, a gametocyte surface protein involved in gamete function, has long been a promising candidate. 28747311 2 40 theme promising 371:379 arg1 candidate 381:389 a promising candidate 369:389 a promising candidate 369:389 Pfs230, a gametocyte surface protein involved in gamete function, has long been a promising candidate. 28747311 11 41 theme biophysical 1621:1631 arg1 results 1652:1658 The biochemical, biophysical, and immunological results 1604:1658 The biochemical, biophysical, and immunological results reported herein 1604:1674 The biochemical, biophysical, and immunological results reported herein support the continued advancement of an N-terminal Pfs230 antigen (Pfs230C1) as a component of a transmission-blocking vaccine. 28747311 3 42 theme 6-Cys 478:482 arg1 motifs 485:490 repeating 6-cysteine (6-Cys) motifs 456:490 repeating 6-cysteine (6-Cys) motifs with a multitude of disulfide bonds 456:526 Due to the large size (3,135 amino acids), complex domains, and repeating 6-cysteine (6-Cys) motifs with a multitude of disulfide bonds, the feasibility of expression of a full-length protein has been difficult. 28747311 9 43 theme disulfide 1291:1299 arg1 analysis 1301:1308 disulfide analysis 1291:1308 disulfide analysis 1291:1308 Peptide mapping and disulfide analysis confirmed the proper formation of predicted disulfide bonds. 28747311 11 44 theme biochemical 1608:1618 arg1 results 1652:1658 The biochemical, biophysical, and immunological results 1604:1658 The biochemical, biophysical, and immunological results reported herein 1604:1674 The biochemical, biophysical, and immunological results reported herein support the continued advancement of an N-terminal Pfs230 antigen (Pfs230C1) as a component of a transmission-blocking vaccine. 28747311 9 45 theme bonds 1364:1368 arg1 formation 1331:1339 the proper formation 1320:1339 the proper formation of predicted disulfide bonds 1320:1368 Peptide mapping and disulfide analysis confirmed the proper formation of predicted disulfide bonds. 28747311 12 46 theme Plasmodium 1923:1932 arg1 proteins 1934:1941 complex Plasmodium proteins 1915:1941 complex Plasmodium proteins 1915:1941 Our results also support the continued use of the scalable baculovirus expression system for the generation of complex Plasmodium proteins. 28747311 10 47 theme immunofluorescence 1449:1466 arg1 assay 1468:1472 an immunofluorescence assay 1446:1472 an immunofluorescence assay (IFA) 1446:1478 Antibodies, generated against Pfs230C1 in mice, bound to the gametocyte in an immunofluorescence assay (IFA) and demonstrated functional activity in both the standard membrane feeding assay (SMFA) and the exflagellation assay (EXA). 28747311 10 47 theme immunofluorescence 1449:1466 arg1 IFA 1475:1477 IFA 1475:1477 IFA 1475:1477 Antibodies, generated against Pfs230C1 in mice, bound to the gametocyte in an immunofluorescence assay (IFA) and demonstrated functional activity in both the standard membrane feeding assay (SMFA) and the exflagellation assay (EXA). 28747311 5 48 theme expression 743:752 arg1 baculovirus 762:772 baculovirus 762:772 baculovirus 762:772 Here we utilized a heterologous expression system, baculovirus, to produce an N-terminal domain of Pfs230 (Pfs230C1). 28747311 5 48 theme expression 743:752 arg1 system 754:759 a heterologous expression system 728:759 a heterologous expression system 728:759 Here we utilized a heterologous expression system, baculovirus, to produce an N-terminal domain of Pfs230 (Pfs230C1). 28747311 9 49 theme proper 1324:1329 arg1 formation 1331:1339 the proper formation 1320:1339 the proper formation of predicted disulfide bonds 1320:1368 Peptide mapping and disulfide analysis confirmed the proper formation of predicted disulfide bonds. 28747311 1 50 contain have 144:147 arg2 potential 153:161 the potential to accelerate malaria parasite elimination by inducing antibodies that block parasite transmission from humans to mosquitoes 149:286 the potential to accelerate malaria parasite elimination by inducing antibodies that block parasite transmission from humans to mosquitoes 149:286 Transmission-blocking vaccines have the potential to accelerate malaria parasite elimination by inducing antibodies that block parasite transmission from humans to mosquitoes. 28747311 1 50 contain have 144:147 arg1 vaccines 135:142 Transmission-blocking vaccines 113:142 Transmission-blocking vaccines 113:142 Transmission-blocking vaccines have the potential to accelerate malaria parasite elimination by inducing antibodies that block parasite transmission from humans to mosquitoes. 28747311 8 51 theme nickel 1099:1104 arg1 affinity 1106:1113 nickel affinity 1099:1113 nickel affinity 1099:1113 The expressed protein, purified by nickel affinity, ion exchange, and size exclusion chromatography to >90% purity, was present in monomeric form with an observed mass of 33,510 Da (matching oxidized form). 28747311 7 52 theme potential 1030:1038 arg1 glycosylation 1049:1061 potential N-linked glycosylation 1030:1061 potential N-linked glycosylation 1030:1061 Since the native host lacks glycosylation machinery, a single N585Q mutation was made to eliminate potential N-linked glycosylation. 28747311 3 53 theme bonds 522:526 arg1 multitude 499:507 a multitude 497:507 a multitude of disulfide bonds 497:526 Due to the large size (3,135 amino acids), complex domains, and repeating 6-cysteine (6-Cys) motifs with a multitude of disulfide bonds, the feasibility of expression of a full-length protein has been difficult. 28747311 9 54 theme disulfide 1354:1362 arg1 bonds 1364:1368 predicted disulfide bonds 1344:1368 predicted disulfide bonds 1344:1368 Peptide mapping and disulfide analysis confirmed the proper formation of predicted disulfide bonds. 28747311 8 55 theme % 1170:1170 arg1 purity 1172:1177 >90% purity 1167:1177 >90% purity 1167:1177 The expressed protein, purified by nickel affinity, ion exchange, and size exclusion chromatography to >90% purity, was present in monomeric form with an observed mass of 33,510 Da (matching oxidized form). 28747311 3 56 with motifs 485:490 arg1 multitude 499:507 a multitude 497:507 a multitude of disulfide bonds 497:526 Due to the large size (3,135 amino acids), complex domains, and repeating 6-cysteine (6-Cys) motifs with a multitude of disulfide bonds, the feasibility of expression of a full-length protein has been difficult. 28747311 12 57 theme baculovirus 1863:1873 arg1 system 1886:1891 the scalable baculovirus expression system 1850:1891 the scalable baculovirus expression system 1850:1891 Our results also support the continued use of the scalable baculovirus expression system for the generation of complex Plasmodium proteins. 28747311 6 58 theme Sf9 920:922 arg1 cells 924:928 Super Sf9 cells 914:928 Super Sf9 cells 914:928 Pfs230C1 (amino acids 443 to 731) with a polyhistidine affinity tag was expressed in Super Sf9 cells. 28747311 12 59 theme system 1886:1891 arg1 use 1843:1845 the continued use 1829:1845 the continued use of the scalable baculovirus expression system for the generation of complex Plasmodium proteins 1829:1941 Our results also support the continued use of the scalable baculovirus expression system for the generation of complex Plasmodium proteins. 28747311 8 60 theme Da 1242:1243 arg1 mass 1227:1230 an observed mass 1215:1230 an observed mass of 33,510 Da (matching oxidized form) 1215:1268 The expressed protein, purified by nickel affinity, ion exchange, and size exclusion chromatography to >90% purity, was present in monomeric form with an observed mass of 33,510 Da (matching oxidized form). 28747311 10 61 theme feeding 1547:1553 arg1 SMFA 1562:1565 SMFA 1562:1565 SMFA 1562:1565 Antibodies, generated against Pfs230C1 in mice, bound to the gametocyte in an immunofluorescence assay (IFA) and demonstrated functional activity in both the standard membrane feeding assay (SMFA) and the exflagellation assay (EXA). 28747311 10 61 theme feeding 1547:1553 arg1 assay 1555:1559 the standard membrane feeding assay 1525:1559 the standard membrane feeding assay (SMFA) 1525:1566 Antibodies, generated against Pfs230C1 in mice, bound to the gametocyte in an immunofluorescence assay (IFA) and demonstrated functional activity in both the standard membrane feeding assay (SMFA) and the exflagellation assay (EXA). 28747311 7 62 theme N585Q 993:997 arg1 mutation 999:1006 a single N585Q mutation 984:1006 a single N585Q mutation 984:1006 Since the native host lacks glycosylation machinery, a single N585Q mutation was made to eliminate potential N-linked glycosylation. 28747311 8 63 theme exclusion 1139:1147 arg1 chromatography 1149:1162 size exclusion chromatography 1134:1162 size exclusion chromatography 1134:1162 The expressed protein, purified by nickel affinity, ion exchange, and size exclusion chromatography to >90% purity, was present in monomeric form with an observed mass of 33,510 Da (matching oxidized form). 28747311 8 64 theme monomeric 1195:1203 arg1 form 1205:1208 monomeric form 1195:1208 monomeric form with an observed mass of 33,510 Da (matching oxidized form) 1195:1268 The expressed protein, purified by nickel affinity, ion exchange, and size exclusion chromatography to >90% purity, was present in monomeric form with an observed mass of 33,510 Da (matching oxidized form). 28747311 10 65 theme standard 1529:1536 arg1 SMFA 1562:1565 SMFA 1562:1565 SMFA 1562:1565 Antibodies, generated against Pfs230C1 in mice, bound to the gametocyte in an immunofluorescence assay (IFA) and demonstrated functional activity in both the standard membrane feeding assay (SMFA) and the exflagellation assay (EXA). 28747311 10 65 theme standard 1529:1536 arg1 assay 1555:1559 the standard membrane feeding assay 1525:1559 the standard membrane feeding assay (SMFA) 1525:1566 Antibodies, generated against Pfs230C1 in mice, bound to the gametocyte in an immunofluorescence assay (IFA) and demonstrated functional activity in both the standard membrane feeding assay (SMFA) and the exflagellation assay (EXA). 28747311 3 66 theme full-length 564:574 arg1 protein 576:582 a full-length protein 562:582 a full-length protein 562:582 Due to the large size (3,135 amino acids), complex domains, and repeating 6-cysteine (6-Cys) motifs with a multitude of disulfide bonds, the feasibility of expression of a full-length protein has been difficult. 28747311 7 67 theme glycosylation 959:971 arg1 machinery 973:981 glycosylation machinery 959:981 glycosylation machinery 959:981 Since the native host lacks glycosylation machinery, a single N585Q mutation was made to eliminate potential N-linked glycosylation. 28747311 10 68 from Pfs230C1 1401:1408 arg1 mice 1413:1416 mice 1413:1416 mice 1413:1416 Antibodies, generated against Pfs230C1 in mice, bound to the gametocyte in an immunofluorescence assay (IFA) and demonstrated functional activity in both the standard membrane feeding assay (SMFA) and the exflagellation assay (EXA). 28747311 11 69 theme Pfs230 1727:1732 arg1 Pfs230C1 1743:1750 Pfs230C1 1743:1750 Pfs230C1 1743:1750 The biochemical, biophysical, and immunological results reported herein support the continued advancement of an N-terminal Pfs230 antigen (Pfs230C1) as a component of a transmission-blocking vaccine. 28747311 11 69 theme Pfs230 1727:1732 arg1 antigen 1734:1740 an N-terminal Pfs230 antigen 1713:1740 an N-terminal Pfs230 antigen (Pfs230C1) 1713:1751 The biochemical, biophysical, and immunological results reported herein support the continued advancement of an N-terminal Pfs230 antigen (Pfs230C1) as a component of a transmission-blocking vaccine. 28747311 3 70 with domains 443:449 arg1 multitude 499:507 a multitude 497:507 a multitude of disulfide bonds 497:526 Due to the large size (3,135 amino acids), complex domains, and repeating 6-cysteine (6-Cys) motifs with a multitude of disulfide bonds, the feasibility of expression of a full-length protein has been difficult. 28747311 2 71 theme gametocyte 299:308 arg1 protein 318:324 a gametocyte surface protein 297:324 a gametocyte surface protein involved in gamete function 297:352 Pfs230, a gametocyte surface protein involved in gamete function, has long been a promising candidate. 28747311 2 71 theme gametocyte 299:308 arg1 Pfs230 289:294 Pfs230 289:294 Pfs230 289:294 Pfs230, a gametocyte surface protein involved in gamete function, has long been a promising candidate. 28747311 4 72 theme N-terminal 689:698 arg1 fragments 700:708 N-terminal fragments 689:708 N-terminal fragments 689:708 A priority focus, therefore, has been on the generation of single domains, including N-terminal fragments. 28747311 0 73 theme Active 65:70 arg1 Candidate 102:110 a Biological Active Transmission-Blocking Vaccine Candidate 52:110 a Biological Active Transmission-Blocking Vaccine Candidate 52:110 N-Terminal Pfs230 Domain Produced in Baculovirus as a Biological Active Transmission-Blocking Vaccine Candidate. 28747311 0 74 theme Vaccine 94:100 arg1 Candidate 102:110 a Biological Active Transmission-Blocking Vaccine Candidate 52:110 a Biological Active Transmission-Blocking Vaccine Candidate 52:110 N-Terminal Pfs230 Domain Produced in Baculovirus as a Biological Active Transmission-Blocking Vaccine Candidate. 28747311 5 75 used utilized 719:726 arg2 we 716:717 we 716:717 we 716:717 Here we utilized a heterologous expression system, baculovirus, to produce an N-terminal domain of Pfs230 (Pfs230C1). 28747311 8 76 from present 1184:1190 arg1 form 1205:1208 monomeric form 1195:1208 monomeric form with an observed mass of 33,510 Da (matching oxidized form) 1195:1268 The expressed protein, purified by nickel affinity, ion exchange, and size exclusion chromatography to >90% purity, was present in monomeric form with an observed mass of 33,510 Da (matching oxidized form). 28747311 1 77 theme parasite 185:192 arg1 elimination 194:204 malaria parasite elimination 177:204 malaria parasite elimination 177:204 Transmission-blocking vaccines have the potential to accelerate malaria parasite elimination by inducing antibodies that block parasite transmission from humans to mosquitoes. 28747311 4 78 theme single 663:668 arg1 domains 670:676 single domains 663:676 single domains 663:676 A priority focus, therefore, has been on the generation of single domains, including N-terminal fragments. 28747311 4 78 theme single 663:668 arg1 fragments 700:708 N-terminal fragments 689:708 N-terminal fragments 689:708 A priority focus, therefore, has been on the generation of single domains, including N-terminal fragments. 28747311 12 79 theme continued 1833:1841 arg1 use 1843:1845 the continued use 1829:1845 the continued use of the scalable baculovirus expression system for the generation of complex Plasmodium proteins 1829:1941 Our results also support the continued use of the scalable baculovirus expression system for the generation of complex Plasmodium proteins. 28747311 2 80 theme gamete 338:343 arg1 function 345:352 gamete function 338:352 gamete function 338:352 Pfs230, a gametocyte surface protein involved in gamete function, has long been a promising candidate. 28747311 8 81 located present 1184:1190 arg2 protein 1078:1084 The expressed protein 1064:1084 The expressed protein 1064:1084 The expressed protein, purified by nickel affinity, ion exchange, and size exclusion chromatography to >90% purity, was present in monomeric form with an observed mass of 33,510 Da (matching oxidized form). 28747311 8 81 located present 1184:1190 arg2 present 1184:1190 present 1184:1190 present 1184:1190 The expressed protein, purified by nickel affinity, ion exchange, and size exclusion chromatography to >90% purity, was present in monomeric form with an observed mass of 33,510 Da (matching oxidized form). 28747311 8 81 located present 1184:1190 arg1 form 1205:1208 monomeric form 1195:1208 monomeric form with an observed mass of 33,510 Da (matching oxidized form) 1195:1268 The expressed protein, purified by nickel affinity, ion exchange, and size exclusion chromatography to >90% purity, was present in monomeric form with an observed mass of 33,510 Da (matching oxidized form). 28747311 1 82 theme parasite 240:247 arg1 transmission 249:260 parasite transmission 240:260 parasite transmission from humans to mosquitoes 240:286 Transmission-blocking vaccines have the potential to accelerate malaria parasite elimination by inducing antibodies that block parasite transmission from humans to mosquitoes. 28747311 0 83 theme Pfs230 11:16 arg1 Domain 18:23 N-Terminal Pfs230 Domain 0:23 N-Terminal Pfs230 Domain 0:23 N-Terminal Pfs230 Domain Produced in Baculovirus as a Biological Active Transmission-Blocking Vaccine Candidate. 28747311 7 84 link N-linked 1040:1047 arg1 glycosylation 1049:1061 potential N-linked glycosylation 1030:1061 potential N-linked glycosylation 1030:1061 Since the native host lacks glycosylation machinery, a single N585Q mutation was made to eliminate potential N-linked glycosylation. 28747311 5 85 theme N-terminal 789:798 arg1 Pfs230 810:815 Pfs230 810:815 Pfs230 (Pfs230C1) 810:826 Here we utilized a heterologous expression system, baculovirus, to produce an N-terminal domain of Pfs230 (Pfs230C1). 28747311 5 85 theme N-terminal 789:798 arg1 domain 800:805 an N-terminal domain 786:805 an N-terminal domain of Pfs230 (Pfs230C1) 786:826 Here we utilized a heterologous expression system, baculovirus, to produce an N-terminal domain of Pfs230 (Pfs230C1). 28747311 1 86 theme Transmission-blocking 113:133 arg1 vaccines 135:142 Transmission-blocking vaccines 113:142 Transmission-blocking vaccines 113:142 Transmission-blocking vaccines have the potential to accelerate malaria parasite elimination by inducing antibodies that block parasite transmission from humans to mosquitoes. 28747311 3 87 theme large 403:407 arg1 size 409:412 the large size 399:412 the large size (3,135 amino acids) 399:432 Due to the large size (3,135 amino acids), complex domains, and repeating 6-cysteine (6-Cys) motifs with a multitude of disulfide bonds, the feasibility of expression of a full-length protein has been difficult. 28747311 3 87 theme large 403:407 arg1 acids 427:431 3,135 amino acids 415:431 3,135 amino acids 415:431 Due to the large size (3,135 amino acids), complex domains, and repeating 6-cysteine (6-Cys) motifs with a multitude of disulfide bonds, the feasibility of expression of a full-length protein has been difficult. 28747311 10 88 theme exflagellation 1576:1589 arg1 EXA 1598:1600 EXA 1598:1600 EXA 1598:1600 Antibodies, generated against Pfs230C1 in mice, bound to the gametocyte in an immunofluorescence assay (IFA) and demonstrated functional activity in both the standard membrane feeding assay (SMFA) and the exflagellation assay (EXA). 28747311 10 88 theme exflagellation 1576:1589 arg1 assay 1591:1595 the exflagellation assay 1572:1595 the exflagellation assay (EXA) 1572:1601 Antibodies, generated against Pfs230C1 in mice, bound to the gametocyte in an immunofluorescence assay (IFA) and demonstrated functional activity in both the standard membrane feeding assay (SMFA) and the exflagellation assay (EXA). 28747311 3 89 theme repeating 456:464 arg1 motifs 485:490 repeating 6-cysteine (6-Cys) motifs 456:490 repeating 6-cysteine (6-Cys) motifs with a multitude of disulfide bonds 456:526 Due to the large size (3,135 amino acids), complex domains, and repeating 6-cysteine (6-Cys) motifs with a multitude of disulfide bonds, the feasibility of expression of a full-length protein has been difficult. 28747311 9 90 theme Peptide 1271:1277 arg1 mapping 1279:1285 Peptide mapping 1271:1285 Peptide mapping 1271:1285 Peptide mapping and disulfide analysis confirmed the proper formation of predicted disulfide bonds. 28747311 3 91 theme amino 421:425 arg1 size 409:412 the large size 399:412 the large size (3,135 amino acids) 399:432 Due to the large size (3,135 amino acids), complex domains, and repeating 6-cysteine (6-Cys) motifs with a multitude of disulfide bonds, the feasibility of expression of a full-length protein has been difficult. 28747311 3 91 theme amino 421:425 arg1 acids 427:431 3,135 amino acids 415:431 3,135 amino acids 415:431 Due to the large size (3,135 amino acids), complex domains, and repeating 6-cysteine (6-Cys) motifs with a multitude of disulfide bonds, the feasibility of expression of a full-length protein has been difficult. 28747311 8 92 theme expressed 1068:1076 arg1 protein 1078:1084 The expressed protein 1064:1084 The expressed protein 1064:1084 The expressed protein, purified by nickel affinity, ion exchange, and size exclusion chromatography to >90% purity, was present in monomeric form with an observed mass of 33,510 Da (matching oxidized form). 28747311 8 92 theme expressed 1068:1076 arg1 present 1184:1190 present 1184:1190 present 1184:1190 The expressed protein, purified by nickel affinity, ion exchange, and size exclusion chromatography to >90% purity, was present in monomeric form with an observed mass of 33,510 Da (matching oxidized form). 28747311 6 93 dep acids 845:849 arg1 to 855:856 to 855:856 to 855:856 Pfs230C1 (amino acids 443 to 731) with a polyhistidine affinity tag was expressed in Super Sf9 cells. 28747311 11 94 theme transmission-blocking 1773:1793 arg1 vaccine 1795:1801 a transmission-blocking vaccine 1771:1801 a transmission-blocking vaccine 1771:1801 The biochemical, biophysical, and immunological results reported herein support the continued advancement of an N-terminal Pfs230 antigen (Pfs230C1) as a component of a transmission-blocking vaccine. 28747311 12 95 theme proteins 1934:1941 arg1 generation 1901:1910 the generation 1897:1910 the generation of complex Plasmodium proteins 1897:1941 Our results also support the continued use of the scalable baculovirus expression system for the generation of complex Plasmodium proteins. 28747311 4 96 theme priority 606:613 arg1 focus 615:619 A priority focus 604:619 A priority focus 604:619 A priority focus, therefore, has been on the generation of single domains, including N-terminal fragments. 28747311 12 97 theme scalable 1854:1861 arg1 system 1886:1891 the scalable baculovirus expression system 1850:1891 the scalable baculovirus expression system 1850:1891 Our results also support the continued use of the scalable baculovirus expression system for the generation of complex Plasmodium proteins. 28747311 3 98 theme disulfide 512:520 arg1 bonds 522:526 disulfide bonds 512:526 disulfide bonds 512:526 Due to the large size (3,135 amino acids), complex domains, and repeating 6-cysteine (6-Cys) motifs with a multitude of disulfide bonds, the feasibility of expression of a full-length protein has been difficult. 26903438 3 0 theme primary 262:268 arg1 unit 280:283 The primary repeating unit 258:283 The primary repeating unit present in chicken egg white KS 258:315 The primary repeating unit present in chicken egg white KS was →4) β-N-acetyl-6-O-sulfo-d-glucosamine (1 → 3) β-d-galactose (1→ with some 6-O-sulfo galactose residues present. 26903438 5 1 theme 2,8- 703:706 arg1 residues 747:754 2,8- and 2,9-linked N-acetylneuraminic acid residues 703:754 2,8- and 2,9-linked N-acetylneuraminic acid residues 703:754 Of particular interest was the presence of substantial amounts of 2,8- and 2,9-linked N-acetylneuraminic acid residues in the form of oligosialic acid terminating the non-reducing ends of the KS chains. 26903438 3 2 theme repeating 270:278 arg1 unit 280:283 The primary repeating unit 258:283 The primary repeating unit present in chicken egg white KS 258:315 The primary repeating unit present in chicken egg white KS was →4) β-N-acetyl-6-O-sulfo-d-glucosamine (1 → 3) β-d-galactose (1→ with some 6-O-sulfo galactose residues present. 26903438 1 3 theme ∼0.06 143:147 arg1 % 151:151 ∼0.06 wt% 143:151 ∼0.06 wt% (dry weight) 143:164 Keratan sulfate (KS) was isolated from chicken egg white in amounts corresponding to ∼0.06 wt% (dry weight). 26903438 1 3 theme ∼0.06 143:147 arg1 weight 158:163 dry weight 154:163 dry weight 154:163 Keratan sulfate (KS) was isolated from chicken egg white in amounts corresponding to ∼0.06 wt% (dry weight). 26903438 5 4 link 2,9-linked 712:721 arg1 residues 747:754 2,8- and 2,9-linked N-acetylneuraminic acid residues 703:754 2,8- and 2,9-linked N-acetylneuraminic acid residues 703:754 Of particular interest was the presence of substantial amounts of 2,8- and 2,9-linked N-acetylneuraminic acid residues in the form of oligosialic acid terminating the non-reducing ends of the KS chains. 26903438 1 5 theme Keratan 58:64 arg1 KS 75:76 KS 75:76 KS 75:76 Keratan sulfate (KS) was isolated from chicken egg white in amounts corresponding to ∼0.06 wt% (dry weight). 26903438 1 5 theme Keratan 58:64 arg1 sulfate 66:72 Keratan sulfate 58:72 Keratan sulfate (KS) 58:77 Keratan sulfate (KS) was isolated from chicken egg white in amounts corresponding to ∼0.06 wt% (dry weight). 26903438 3 6 theme white 308:312 arg1 egg 304:306 chicken egg white 296:312 chicken egg white 296:312 The primary repeating unit present in chicken egg white KS was →4) β-N-acetyl-6-O-sulfo-d-glucosamine (1 → 3) β-d-galactose (1→ with some 6-O-sulfo galactose residues present. 26903438 3 7 attach present 285:291 arg2 KS 314:315 The primary repeating unit present in chicken egg white KS 258:315 The primary repeating unit present in chicken egg white KS 258:315 The primary repeating unit present in chicken egg white KS was →4) β-N-acetyl-6-O-sulfo-d-glucosamine (1 → 3) β-d-galactose (1→ with some 6-O-sulfo galactose residues present. 26903438 3 7 attach present 285:291 arg1 egg 304:306 chicken egg white 296:312 chicken egg white 296:312 The primary repeating unit present in chicken egg white KS was →4) β-N-acetyl-6-O-sulfo-d-glucosamine (1 → 3) β-d-galactose (1→ with some 6-O-sulfo galactose residues present. 26903438 5 8 theme non-reducing 804:815 arg1 ends 817:820 the non-reducing ends 800:820 the non-reducing ends of the KS chains 800:837 Of particular interest was the presence of substantial amounts of 2,8- and 2,9-linked N-acetylneuraminic acid residues in the form of oligosialic acid terminating the non-reducing ends of the KS chains. 26903438 3 9 dep β-N-acetyl-6-O-sulfo-d-glucosamine 325:358 arg1 →4 321:322 →4 321:322 →4 321:322 The primary repeating unit present in chicken egg white KS was →4) β-N-acetyl-6-O-sulfo-d-glucosamine (1 → 3) β-d-galactose (1→ with some 6-O-sulfo galactose residues present. 26903438 4 10 theme oxygen 571:576 arg1 species 578:584 reactive oxygen species 562:584 reactive oxygen species generated using copper (II) and hydrogen peroxide 562:634 This KS was somewhat resistant to depolymerization using keratanase 1 but could be depolymerized efficiently through the use of reactive oxygen species generated using copper (II) and hydrogen peroxide. 26903438 1 11 theme wt 149:150 arg1 % 151:151 ∼0.06 wt% 143:151 ∼0.06 wt% (dry weight) 143:164 Keratan sulfate (KS) was isolated from chicken egg white in amounts corresponding to ∼0.06 wt% (dry weight). 26903438 1 11 theme wt 149:150 arg1 weight 158:163 dry weight 154:163 dry weight 154:163 Keratan sulfate (KS) was isolated from chicken egg white in amounts corresponding to ∼0.06 wt% (dry weight). 26903438 3 12 theme chicken 296:302 arg1 egg 304:306 chicken egg white 296:312 chicken egg white 296:312 The primary repeating unit present in chicken egg white KS was →4) β-N-acetyl-6-O-sulfo-d-glucosamine (1 → 3) β-d-galactose (1→ with some 6-O-sulfo galactose residues present. 26903438 0 13 from egg 47:49 arg1 glycosaminoglycan 16:32 Keratan sulfate glycosaminoglycan 0:32 Keratan sulfate glycosaminoglycan from chicken egg white. 0:56 Keratan sulfate glycosaminoglycan from chicken egg white. 26903438 2 14 theme kDa 223:225 arg1 weight 206:211 a weight-average molecular weight 179:211 a weight-average molecular weight of ∼36-41 kDa 179:225 This KS had a weight-average molecular weight of ∼36-41 kDa with a polydispersity of ∼1.3. 26903438 0 15 theme sulfate 8:14 arg1 glycosaminoglycan 16:32 Keratan sulfate glycosaminoglycan 0:32 Keratan sulfate glycosaminoglycan from chicken egg white. 0:56 Keratan sulfate glycosaminoglycan from chicken egg white. 26903438 5 16 theme amounts 692:698 arg1 presence 668:675 the presence 664:675 the presence of substantial amounts of 2,8- and 2,9-linked N-acetylneuraminic acid residues in the form of oligosialic acid terminating the non-reducing ends of the KS chains 664:837 Of particular interest was the presence of substantial amounts of 2,8- and 2,9-linked N-acetylneuraminic acid residues in the form of oligosialic acid terminating the non-reducing ends of the KS chains. 26903438 0 17 theme Keratan 0:6 arg1 glycosaminoglycan 16:32 Keratan sulfate glycosaminoglycan 0:32 Keratan sulfate glycosaminoglycan from chicken egg white. 0:56 Keratan sulfate glycosaminoglycan from chicken egg white. 26903438 1 18 theme dry 154:156 arg1 % 151:151 ∼0.06 wt% 143:151 ∼0.06 wt% (dry weight) 143:164 Keratan sulfate (KS) was isolated from chicken egg white in amounts corresponding to ∼0.06 wt% (dry weight). 26903438 1 18 theme dry 154:156 arg1 weight 158:163 dry weight 154:163 dry weight 154:163 Keratan sulfate (KS) was isolated from chicken egg white in amounts corresponding to ∼0.06 wt% (dry weight). 26903438 1 19 from egg 105:107 arg1 amounts 118:124 amounts 118:124 amounts corresponding to ∼0.06 wt% (dry weight) 118:164 Keratan sulfate (KS) was isolated from chicken egg white in amounts corresponding to ∼0.06 wt% (dry weight). 26903438 2 20 theme ∼1.3 252:255 arg1 polydispersity 234:247 a polydispersity 232:247 a polydispersity of ∼1.3 232:255 This KS had a weight-average molecular weight of ∼36-41 kDa with a polydispersity of ∼1.3. 26903438 6 21 attach N-linked 869:876 arg1 core 891:894 a protein core 881:894 a protein core 881:894 Most of the KS appears to be N-linked to a protein core as evidenced by its sensitivity to PNGase F. 26903438 6 21 attach N-linked 869:876 arg2 KS 852:853 the KS 848:853 the KS 848:853 Most of the KS appears to be N-linked to a protein core as evidenced by its sensitivity to PNGase F. 26903438 6 21 attach N-linked 869:876 arg2 Most 840:843 Most 840:843 Most 840:843 Most of the KS appears to be N-linked to a protein core as evidenced by its sensitivity to PNGase F. 26903438 4 22 theme species 578:584 arg1 use 555:557 the use 551:557 the use of reactive oxygen species generated using copper (II) and hydrogen peroxide 551:634 This KS was somewhat resistant to depolymerization using keratanase 1 but could be depolymerized efficiently through the use of reactive oxygen species generated using copper (II) and hydrogen peroxide. 26903438 6 23 theme protein 883:889 arg1 core 891:894 a protein core 881:894 a protein core 881:894 Most of the KS appears to be N-linked to a protein core as evidenced by its sensitivity to PNGase F. 26903438 5 24 theme particular 640:649 arg1 interest 651:658 particular interest 640:658 particular interest 640:658 Of particular interest was the presence of substantial amounts of 2,8- and 2,9-linked N-acetylneuraminic acid residues in the form of oligosialic acid terminating the non-reducing ends of the KS chains. 26903438 3 25 theme 6-O-sulfo 396:404 arg1 residues 416:423 some 6-O-sulfo galactose residues 391:423 some 6-O-sulfo galactose residues 391:423 The primary repeating unit present in chicken egg white KS was →4) β-N-acetyl-6-O-sulfo-d-glucosamine (1 → 3) β-d-galactose (1→ with some 6-O-sulfo galactose residues present. 26903438 5 26 theme 2,9-linked 712:721 arg1 residues 747:754 2,8- and 2,9-linked N-acetylneuraminic acid residues 703:754 2,8- and 2,9-linked N-acetylneuraminic acid residues 703:754 Of particular interest was the presence of substantial amounts of 2,8- and 2,9-linked N-acetylneuraminic acid residues in the form of oligosialic acid terminating the non-reducing ends of the KS chains. 26903438 5 27 theme interest 651:658 arg1 presence 668:675 the presence 664:675 the presence of substantial amounts of 2,8- and 2,9-linked N-acetylneuraminic acid residues in the form of oligosialic acid terminating the non-reducing ends of the KS chains 664:837 Of particular interest was the presence of substantial amounts of 2,8- and 2,9-linked N-acetylneuraminic acid residues in the form of oligosialic acid terminating the non-reducing ends of the KS chains. 26903438 2 28 theme weight-average 181:194 arg1 weight 206:211 a weight-average molecular weight 179:211 a weight-average molecular weight of ∼36-41 kDa 179:225 This KS had a weight-average molecular weight of ∼36-41 kDa with a polydispersity of ∼1.3. 26903438 0 29 theme chicken 39:45 arg1 egg 47:49 chicken egg white 39:55 chicken egg white 39:55 Keratan sulfate glycosaminoglycan from chicken egg white. 26903438 5 30 theme N-acetylneuraminic 723:740 arg1 residues 747:754 2,8- and 2,9-linked N-acetylneuraminic acid residues 703:754 2,8- and 2,9-linked N-acetylneuraminic acid residues 703:754 Of particular interest was the presence of substantial amounts of 2,8- and 2,9-linked N-acetylneuraminic acid residues in the form of oligosialic acid terminating the non-reducing ends of the KS chains. 26903438 3 31 from egg 304:306 arg1 present 285:291 present 285:291 present 285:291 The primary repeating unit present in chicken egg white KS was →4) β-N-acetyl-6-O-sulfo-d-glucosamine (1 → 3) β-d-galactose (1→ with some 6-O-sulfo galactose residues present. 26903438 6 32 theme PNGase 931:936 arg1 F 938:938 PNGase F 931:938 PNGase F 931:938 Most of the KS appears to be N-linked to a protein core as evidenced by its sensitivity to PNGase F. 26903438 5 33 theme substantial 680:690 arg1 residues 747:754 2,8- and 2,9-linked N-acetylneuraminic acid residues 703:754 2,8- and 2,9-linked N-acetylneuraminic acid residues 703:754 Of particular interest was the presence of substantial amounts of 2,8- and 2,9-linked N-acetylneuraminic acid residues in the form of oligosialic acid terminating the non-reducing ends of the KS chains. 26903438 5 33 theme substantial 680:690 arg1 amounts 692:698 substantial amounts 680:698 substantial amounts of 2,8- and 2,9-linked N-acetylneuraminic acid residues 680:754 Of particular interest was the presence of substantial amounts of 2,8- and 2,9-linked N-acetylneuraminic acid residues in the form of oligosialic acid terminating the non-reducing ends of the KS chains. 26903438 3 34 theme β-N-acetyl-6-O-sulfo-d-glucosamine 325:358 arg1 β-d-galactose 368:380 →4) β-N-acetyl-6-O-sulfo-d-glucosamine (1 → 3) β-d-galactose 321:380 →4) β-N-acetyl-6-O-sulfo-d-glucosamine (1 → 3) β-d-galactose (1→ with some 6-O-sulfo galactose residues 321:423 The primary repeating unit present in chicken egg white KS was →4) β-N-acetyl-6-O-sulfo-d-glucosamine (1 → 3) β-d-galactose (1→ with some 6-O-sulfo galactose residues present. 26903438 5 35 theme KS 829:830 arg1 chains 832:837 the KS chains 825:837 the KS chains 825:837 Of particular interest was the presence of substantial amounts of 2,8- and 2,9-linked N-acetylneuraminic acid residues in the form of oligosialic acid terminating the non-reducing ends of the KS chains. 26903438 5 36 theme residues 747:754 arg1 residues 747:754 2,8- and 2,9-linked N-acetylneuraminic acid residues 703:754 2,8- and 2,9-linked N-acetylneuraminic acid residues 703:754 Of particular interest was the presence of substantial amounts of 2,8- and 2,9-linked N-acetylneuraminic acid residues in the form of oligosialic acid terminating the non-reducing ends of the KS chains. 26903438 5 36 theme residues 747:754 arg1 amounts 692:698 substantial amounts 680:698 substantial amounts of 2,8- and 2,9-linked N-acetylneuraminic acid residues 680:754 Of particular interest was the presence of substantial amounts of 2,8- and 2,9-linked N-acetylneuraminic acid residues in the form of oligosialic acid terminating the non-reducing ends of the KS chains. 26903438 5 37 from presence 668:675 arg1 form 763:766 the form 759:766 the form of oligosialic acid terminating the non-reducing ends of the KS chains 759:837 Of particular interest was the presence of substantial amounts of 2,8- and 2,9-linked N-acetylneuraminic acid residues in the form of oligosialic acid terminating the non-reducing ends of the KS chains. 26903438 3 38 dep β-d-galactose 368:380 arg1 1→ 383:384 1→ 383:384 →4) β-N-acetyl-6-O-sulfo-d-glucosamine (1 → 3) β-d-galactose (1→ with some 6-O-sulfo galactose residues 321:423 The primary repeating unit present in chicken egg white KS was →4) β-N-acetyl-6-O-sulfo-d-glucosamine (1 → 3) β-d-galactose (1→ with some 6-O-sulfo galactose residues present. 26903438 1 39 theme chicken 97:103 arg1 egg 105:107 chicken egg white 97:113 chicken egg white in amounts corresponding to ∼0.06 wt% (dry weight) 97:164 Keratan sulfate (KS) was isolated from chicken egg white in amounts corresponding to ∼0.06 wt% (dry weight). 26903438 0 40 theme white 51:55 arg1 egg 47:49 chicken egg white 39:55 chicken egg white 39:55 Keratan sulfate glycosaminoglycan from chicken egg white. 26903438 3 41 theme galactose 406:414 arg1 residues 416:423 some 6-O-sulfo galactose residues 391:423 some 6-O-sulfo galactose residues 391:423 The primary repeating unit present in chicken egg white KS was →4) β-N-acetyl-6-O-sulfo-d-glucosamine (1 → 3) β-d-galactose (1→ with some 6-O-sulfo galactose residues present. 26903438 1 42 attach isolated 83:90 arg2 KS 75:76 KS 75:76 KS 75:76 Keratan sulfate (KS) was isolated from chicken egg white in amounts corresponding to ∼0.06 wt% (dry weight). 26903438 1 42 attach isolated 83:90 arg1 egg 105:107 chicken egg white 97:113 chicken egg white in amounts corresponding to ∼0.06 wt% (dry weight) 97:164 Keratan sulfate (KS) was isolated from chicken egg white in amounts corresponding to ∼0.06 wt% (dry weight). 26903438 1 42 attach isolated 83:90 arg2 sulfate 66:72 Keratan sulfate 58:72 Keratan sulfate (KS) 58:77 Keratan sulfate (KS) was isolated from chicken egg white in amounts corresponding to ∼0.06 wt% (dry weight). 26903438 3 43 with β-d-galactose 368:380 arg1 residues 416:423 some 6-O-sulfo galactose residues 391:423 some 6-O-sulfo galactose residues 391:423 The primary repeating unit present in chicken egg white KS was →4) β-N-acetyl-6-O-sulfo-d-glucosamine (1 → 3) β-d-galactose (1→ with some 6-O-sulfo galactose residues present. 26903438 5 44 theme acid 742:745 arg1 residues 747:754 2,8- and 2,9-linked N-acetylneuraminic acid residues 703:754 2,8- and 2,9-linked N-acetylneuraminic acid residues 703:754 Of particular interest was the presence of substantial amounts of 2,8- and 2,9-linked N-acetylneuraminic acid residues in the form of oligosialic acid terminating the non-reducing ends of the KS chains. 26903438 1 45 theme white 109:113 arg1 egg 105:107 chicken egg white 97:113 chicken egg white in amounts corresponding to ∼0.06 wt% (dry weight) 97:164 Keratan sulfate (KS) was isolated from chicken egg white in amounts corresponding to ∼0.06 wt% (dry weight). 26903438 5 46 attach presence 668:675 arg2 residues 747:754 2,8- and 2,9-linked N-acetylneuraminic acid residues 703:754 2,8- and 2,9-linked N-acetylneuraminic acid residues 703:754 Of particular interest was the presence of substantial amounts of 2,8- and 2,9-linked N-acetylneuraminic acid residues in the form of oligosialic acid terminating the non-reducing ends of the KS chains. 26903438 5 46 attach presence 668:675 arg2 interest 651:658 particular interest 640:658 particular interest 640:658 Of particular interest was the presence of substantial amounts of 2,8- and 2,9-linked N-acetylneuraminic acid residues in the form of oligosialic acid terminating the non-reducing ends of the KS chains. 26903438 5 46 attach presence 668:675 arg1 form 763:766 the form 759:766 the form of oligosialic acid terminating the non-reducing ends of the KS chains 759:837 Of particular interest was the presence of substantial amounts of 2,8- and 2,9-linked N-acetylneuraminic acid residues in the form of oligosialic acid terminating the non-reducing ends of the KS chains. 26903438 5 46 attach presence 668:675 arg2 amounts 692:698 substantial amounts 680:698 substantial amounts of 2,8- and 2,9-linked N-acetylneuraminic acid residues 680:754 Of particular interest was the presence of substantial amounts of 2,8- and 2,9-linked N-acetylneuraminic acid residues in the form of oligosialic acid terminating the non-reducing ends of the KS chains. 26903438 5 47 theme acid 783:786 arg1 form 763:766 the form 759:766 the form of oligosialic acid terminating the non-reducing ends of the KS chains 759:837 Of particular interest was the presence of substantial amounts of 2,8- and 2,9-linked N-acetylneuraminic acid residues in the form of oligosialic acid terminating the non-reducing ends of the KS chains. 26903438 2 48 contain had 175:177 arg1 KS 172:173 This KS 167:173 This KS 167:173 This KS had a weight-average molecular weight of ∼36-41 kDa with a polydispersity of ∼1.3. 26903438 2 48 contain had 175:177 arg2 weight 206:211 a weight-average molecular weight 179:211 a weight-average molecular weight of ∼36-41 kDa 179:225 This KS had a weight-average molecular weight of ∼36-41 kDa with a polydispersity of ∼1.3. 26903438 3 49 theme unit 280:283 arg1 KS 314:315 The primary repeating unit present in chicken egg white KS 258:315 The primary repeating unit present in chicken egg white KS 258:315 The primary repeating unit present in chicken egg white KS was →4) β-N-acetyl-6-O-sulfo-d-glucosamine (1 → 3) β-d-galactose (1→ with some 6-O-sulfo galactose residues present. 26903438 3 50 from present 285:291 arg1 egg 304:306 chicken egg white 296:312 chicken egg white 296:312 The primary repeating unit present in chicken egg white KS was →4) β-N-acetyl-6-O-sulfo-d-glucosamine (1 → 3) β-d-galactose (1→ with some 6-O-sulfo galactose residues present. 26903438 5 51 theme oligosialic 771:781 arg1 acid 783:786 oligosialic acid 771:786 oligosialic acid terminating the non-reducing ends of the KS chains 771:837 Of particular interest was the presence of substantial amounts of 2,8- and 2,9-linked N-acetylneuraminic acid residues in the form of oligosialic acid terminating the non-reducing ends of the KS chains. 26903438 4 52 theme hydrogen 618:625 arg1 peroxide 627:634 hydrogen peroxide 618:634 hydrogen peroxide 618:634 This KS was somewhat resistant to depolymerization using keratanase 1 but could be depolymerized efficiently through the use of reactive oxygen species generated using copper (II) and hydrogen peroxide. 26903438 4 53 theme reactive 562:569 arg1 species 578:584 reactive oxygen species 562:584 reactive oxygen species generated using copper (II) and hydrogen peroxide 562:634 This KS was somewhat resistant to depolymerization using keratanase 1 but could be depolymerized efficiently through the use of reactive oxygen species generated using copper (II) and hydrogen peroxide. 26903438 3 54 theme present 285:291 arg1 KS 314:315 The primary repeating unit present in chicken egg white KS 258:315 The primary repeating unit present in chicken egg white KS 258:315 The primary repeating unit present in chicken egg white KS was →4) β-N-acetyl-6-O-sulfo-d-glucosamine (1 → 3) β-d-galactose (1→ with some 6-O-sulfo galactose residues present. 26903438 2 55 theme molecular 196:204 arg1 weight 206:211 a weight-average molecular weight 179:211 a weight-average molecular weight of ∼36-41 kDa 179:225 This KS had a weight-average molecular weight of ∼36-41 kDa with a polydispersity of ∼1.3. 26903438 5 56 theme chains 832:837 arg1 ends 817:820 the non-reducing ends 800:820 the non-reducing ends of the KS chains 800:837 Of particular interest was the presence of substantial amounts of 2,8- and 2,9-linked N-acetylneuraminic acid residues in the form of oligosialic acid terminating the non-reducing ends of the KS chains. 26842584 6 0 theme unreduced 1133:1141 arg1 glycans 1143:1149 the unreduced glycans 1129:1149 the unreduced glycans with the exception that the prominent (2,4) A cleavage ion from the reducing terminus was replaced by a prominent [M-H3 PO4](-) ion 1129:1281 Estimated collisional cross sections were measured with dextran as the calibrant, RESULTS Fragment ions were similar to those from the unreduced glycans with the exception that the prominent (2,4) A cleavage ion from the reducing terminus was replaced by a prominent [M-H3 PO4](-) ion. 26842584 4 1 theme mobility 581:588 arg1 properties 590:599 the ion mobility properties 573:599 the ion mobility properties of N-glycans 573:612 We examined the effect of reduction on the production of diagnostic fragment ions and on the ion mobility properties of N-glycans. 26842584 10 2 theme unreduced 1916:1924 arg1 glycans 1926:1932 the unreduced glycans 1912:1932 the unreduced glycans 1912:1932 CONCLUSIONS Reduction of the reducing terminal GlcNAc residue resulted in fewer diagnostic ions from the chitobiose core but fragmentation of the remainder of the molecules generally paralleled that of the unreduced glycans. 26842584 5 3 theme ribonuclease 680:691 arg1 B 693:693 ribonuclease B 680:693 ribonuclease B 680:693 METHODS Released N-glycans from the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin were reduced with sodium cyanoborohydride and both negative ion CID spectra and ion mobility properties of their phosphate adducts were examined with a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer with electrospray sample introduction. 26842584 5 3 theme ribonuclease 680:691 arg1 glycoproteins 651:663 the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin 647:739 the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin 647:739 METHODS Released N-glycans from the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin were reduced with sodium cyanoborohydride and both negative ion CID spectra and ion mobility properties of their phosphate adducts were examined with a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer with electrospray sample introduction. 26842584 2 4 theme residues 298:305 arg1 location 286:293 location 286:293 location of residues such as fucose 286:320 RATIONALE Negative ion collision-induced dissociation (CID) spectra of released N-glycans provide very informative structural information relating to branching patterns and location of residues such as fucose. 26842584 2 4 theme residues 298:305 arg1 patterns 273:280 branching patterns 263:280 branching patterns 263:280 RATIONALE Negative ion collision-induced dissociation (CID) spectra of released N-glycans provide very informative structural information relating to branching patterns and location of residues such as fucose. 26842584 6 5 theme cleavage 1197:1204 arg1 ion 1206:1208 A cleavage ion 1195:1208 the prominent (2,4) A cleavage ion from the reducing terminus 1175:1235 Estimated collisional cross sections were measured with dextran as the calibrant, RESULTS Fragment ions were similar to those from the unreduced glycans with the exception that the prominent (2,4) A cleavage ion from the reducing terminus was replaced by a prominent [M-H3 PO4](-) ion. 26842584 2 6 theme collision-induced 136:152 arg1 spectra 173:179 RATIONALE Negative ion collision-induced dissociation (CID) spectra 113:179 RATIONALE Negative ion collision-induced dissociation (CID) spectra of released N-glycans 113:201 RATIONALE Negative ion collision-induced dissociation (CID) spectra of released N-glycans provide very informative structural information relating to branching patterns and location of residues such as fucose. 26842584 10 7 theme terminal 1748:1755 arg1 residue 1764:1770 the reducing terminal GlcNAc residue 1735:1770 the reducing terminal GlcNAc residue 1735:1770 CONCLUSIONS Reduction of the reducing terminal GlcNAc residue resulted in fewer diagnostic ions from the chitobiose core but fragmentation of the remainder of the molecules generally paralleled that of the unreduced glycans. 26842584 6 8 with glycans 1143:1149 arg1 exception 1160:1168 the exception that the prominent (2,4) A cleavage ion from the reducing terminus was replaced by a prominent [M-H3 PO4](-) ion 1156:1281 the exception that the prominent (2,4) A cleavage ion from the reducing terminus was replaced by a prominent [M-H3 PO4](-) ion 1156:1281 Estimated collisional cross sections were measured with dextran as the calibrant, RESULTS Fragment ions were similar to those from the unreduced glycans with the exception that the prominent (2,4) A cleavage ion from the reducing terminus was replaced by a prominent [M-H3 PO4](-) ion. 26842584 6 9 theme [M-H3 1265:1269 arg1 ion 1279:1281 a prominent [M-H3 PO4](-) ion 1253:1281 a prominent [M-H3 PO4](-) ion 1253:1281 Estimated collisional cross sections were measured with dextran as the calibrant, RESULTS Fragment ions were similar to those from the unreduced glycans with the exception that the prominent (2,4) A cleavage ion from the reducing terminus was replaced by a prominent [M-H3 PO4](-) ion. 26842584 10 10 theme diagnostic 1790:1799 arg1 ions 1801:1804 fewer diagnostic ions 1784:1804 fewer diagnostic ions from the chitobiose core 1784:1829 CONCLUSIONS Reduction of the reducing terminal GlcNAc residue resulted in fewer diagnostic ions from the chitobiose core but fragmentation of the remainder of the molecules generally paralleled that of the unreduced glycans. 26842584 5 11 theme Waters 893:898 arg1 spectrometer 946:957 a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer 891:957 a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer 891:957 METHODS Released N-glycans from the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin were reduced with sodium cyanoborohydride and both negative ion CID spectra and ion mobility properties of their phosphate adducts were examined with a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer with electrospray sample introduction. 26842584 6 12 theme cross 1020:1024 arg1 calibrant 1069:1077 the calibrant 1065:1077 the calibrant 1065:1077 Estimated collisional cross sections were measured with dextran as the calibrant, RESULTS Fragment ions were similar to those from the unreduced glycans with the exception that the prominent (2,4) A cleavage ion from the reducing terminus was replaced by a prominent [M-H3 PO4](-) ion. 26842584 6 12 theme cross 1020:1024 arg1 sections 1026:1033 Estimated collisional cross sections 998:1033 Estimated collisional cross sections 998:1033 Estimated collisional cross sections were measured with dextran as the calibrant, RESULTS Fragment ions were similar to those from the unreduced glycans with the exception that the prominent (2,4) A cleavage ion from the reducing terminus was replaced by a prominent [M-H3 PO4](-) ion. 26842584 9 13 theme anomer 1691:1696 arg1 separation 1698:1707 anomer separation 1691:1707 anomer separation 1691:1707 This observation showed that this asymmetry was due to anomer separation. 26842584 7 14 theme unreduced 1381:1389 arg1 glycans 1391:1397 the unreduced glycans 1377:1397 the unreduced glycans 1377:1397 Other ions arising from the chitobiose core were of lower relative abundance than those from the unreduced glycans. 26842584 11 15 theme core 2030:2033 arg1 GlcNAc 2035:2040 the core GlcNAc 2026:2040 the core GlcNAc 2026:2040 Thus, most structural information, with the exception of the linkage position of fucose on the core GlcNAc, was available. 26842584 5 16 theme phosphate 854:862 arg1 adducts 864:870 their phosphate adducts 848:870 their phosphate adducts 848:870 METHODS Released N-glycans from the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin were reduced with sodium cyanoborohydride and both negative ion CID spectra and ion mobility properties of their phosphate adducts were examined with a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer with electrospray sample introduction. 26842584 6 17 theme Estimated 998:1006 arg1 calibrant 1069:1077 the calibrant 1065:1077 the calibrant 1065:1077 Estimated collisional cross sections were measured with dextran as the calibrant, RESULTS Fragment ions were similar to those from the unreduced glycans with the exception that the prominent (2,4) A cleavage ion from the reducing terminus was replaced by a prominent [M-H3 PO4](-) ion. 26842584 6 17 theme Estimated 998:1006 arg1 sections 1026:1033 Estimated collisional cross sections 998:1033 Estimated collisional cross sections 998:1033 Estimated collisional cross sections were measured with dextran as the calibrant, RESULTS Fragment ions were similar to those from the unreduced glycans with the exception that the prominent (2,4) A cleavage ion from the reducing terminus was replaced by a prominent [M-H3 PO4](-) ion. 26842584 0 18 from carbohydrates 73:85 arg1 Fragmentation 0:12 Fragmentation 0:12 Fragmentation 0:12 Fragmentation and ion mobility properties of negative ions from N-linked carbohydrates: Part 7. 26842584 0 18 from carbohydrates 73:85 arg1 properties 31:40 ion mobility properties 18:40 ion mobility properties 18:40 Fragmentation and ion mobility properties of negative ions from N-linked carbohydrates: Part 7. 26842584 0 18 from carbohydrates 73:85 arg1 ions 54:57 negative ions 45:57 negative ions from N-linked carbohydrates 45:85 Fragmentation and ion mobility properties of negative ions from N-linked carbohydrates: Part 7. 26842584 6 19 theme prominent 1255:1263 arg1 ion 1279:1281 a prominent [M-H3 PO4](-) ion 1253:1281 a prominent [M-H3 PO4](-) ion 1253:1281 Estimated collisional cross sections were measured with dextran as the calibrant, RESULTS Fragment ions were similar to those from the unreduced glycans with the exception that the prominent (2,4) A cleavage ion from the reducing terminus was replaced by a prominent [M-H3 PO4](-) ion. 26842584 5 20 gly glycoproteins 651:663 arg1 fetuin 672:677 bovine fetuin 665:677 bovine fetuin 665:677 METHODS Released N-glycans from the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin were reduced with sodium cyanoborohydride and both negative ion CID spectra and ion mobility properties of their phosphate adducts were examined with a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer with electrospray sample introduction. 26842584 5 20 gly glycoproteins 651:663 arg1 B 693:693 ribonuclease B 680:693 ribonuclease B 680:693 METHODS Released N-glycans from the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin were reduced with sodium cyanoborohydride and both negative ion CID spectra and ion mobility properties of their phosphate adducts were examined with a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer with electrospray sample introduction. 26842584 5 20 gly glycoproteins 651:663 arg1 glycoproteins 651:663 the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin 647:739 the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin 647:739 METHODS Released N-glycans from the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin were reduced with sodium cyanoborohydride and both negative ion CID spectra and ion mobility properties of their phosphate adducts were examined with a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer with electrospray sample introduction. 26842584 5 20 gly glycoproteins 651:663 arg1 ovalbumin 704:712 chicken ovalbumin 696:712 chicken ovalbumin 696:712 METHODS Released N-glycans from the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin were reduced with sodium cyanoborohydride and both negative ion CID spectra and ion mobility properties of their phosphate adducts were examined with a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer with electrospray sample introduction. 26842584 5 20 gly glycoproteins 651:663 arg1 thyroglobulin 727:739 porcine thyroglobulin 719:739 porcine thyroglobulin 719:739 METHODS Released N-glycans from the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin were reduced with sodium cyanoborohydride and both negative ion CID spectra and ion mobility properties of their phosphate adducts were examined with a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer with electrospray sample introduction. 26842584 8 21 theme prominent 1615:1623 arg1 asymmetry 1625:1633 prominent asymmetry 1615:1633 prominent asymmetry 1615:1633 Estimated collisional cross sections were similar to those of the unreduced compounds but with symmetrical arrival time distribution (ATD) profiles, unlike those of the unreduced glycans whose peaks often contained prominent asymmetry. 26842584 10 22 theme chitobiose 1815:1824 arg1 core 1826:1829 the chitobiose core 1811:1829 the chitobiose core 1811:1829 CONCLUSIONS Reduction of the reducing terminal GlcNAc residue resulted in fewer diagnostic ions from the chitobiose core but fragmentation of the remainder of the molecules generally paralleled that of the unreduced glycans. 26842584 2 23 theme informative 216:226 arg1 information 239:249 very informative structural information 211:249 very informative structural information relating to branching patterns and location of residues such as fucose 211:320 RATIONALE Negative ion collision-induced dissociation (CID) spectra of released N-glycans provide very informative structural information relating to branching patterns and location of residues such as fucose. 26842584 5 24 theme mass 941:944 arg1 spectrometer 946:957 a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer 891:957 a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer 891:957 METHODS Released N-glycans from the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin were reduced with sodium cyanoborohydride and both negative ion CID spectra and ion mobility properties of their phosphate adducts were examined with a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer with electrospray sample introduction. 26842584 7 25 theme relative 1342:1349 arg1 abundance 1351:1359 lower relative abundance 1336:1359 lower relative abundance 1336:1359 Other ions arising from the chitobiose core were of lower relative abundance than those from the unreduced glycans. 26842584 12 26 with symmetrical 2073:2083 arg1 result 2094:2099 the result that cross sections were more appropriate for data-base searching than those from the non-reduced compounds where asymmetry produced lower precision in the measurement 2090:2267 the result that cross sections were more appropriate for data-base searching than those from the non-reduced compounds where asymmetry produced lower precision in the measurement 2090:2267 ATD peaks were symmetrical with the result that cross sections were more appropriate for data-base searching than those from the non-reduced compounds where asymmetry produced lower precision in the measurement. 26842584 11 27 theme linkage 1996:2002 arg1 position 2004:2011 the linkage position 1992:2011 the linkage position of fucose on the core GlcNAc 1992:2040 Thus, most structural information, with the exception of the linkage position of fucose on the core GlcNAc, was available. 26842584 6 28 theme reducing 1219:1226 arg1 terminus 1228:1235 the reducing terminus 1215:1235 the reducing terminus 1215:1235 Estimated collisional cross sections were measured with dextran as the calibrant, RESULTS Fragment ions were similar to those from the unreduced glycans with the exception that the prominent (2,4) A cleavage ion from the reducing terminus was replaced by a prominent [M-H3 PO4](-) ion. 26842584 5 29 theme G2Si 907:910 arg1 spectrometer 946:957 a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer 891:957 a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer 891:957 METHODS Released N-glycans from the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin were reduced with sodium cyanoborohydride and both negative ion CID spectra and ion mobility properties of their phosphate adducts were examined with a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer with electrospray sample introduction. 26842584 12 30 theme ATD 2058:2060 arg1 peaks 2062:2066 ATD peaks 2058:2066 ATD peaks 2058:2066 ATD peaks were symmetrical with the result that cross sections were more appropriate for data-base searching than those from the non-reduced compounds where asymmetry produced lower precision in the measurement. 26842584 5 31 theme negative 792:799 arg1 spectra 809:815 negative ion CID spectra 792:815 negative ion CID spectra 792:815 METHODS Released N-glycans from the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin were reduced with sodium cyanoborohydride and both negative ion CID spectra and ion mobility properties of their phosphate adducts were examined with a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer with electrospray sample introduction. 26842584 5 32 theme ion 928:930 arg1 spectrometer 946:957 a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer 891:957 a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer 891:957 METHODS Released N-glycans from the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin were reduced with sodium cyanoborohydride and both negative ion CID spectra and ion mobility properties of their phosphate adducts were examined with a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer with electrospray sample introduction. 26842584 8 33 theme arrival 1507:1513 arg1 profiles 1539:1546 symmetrical arrival time distribution (ATD) profiles 1495:1546 symmetrical arrival time distribution (ATD) profiles 1495:1546 Estimated collisional cross sections were similar to those of the unreduced compounds but with symmetrical arrival time distribution (ATD) profiles, unlike those of the unreduced glycans whose peaks often contained prominent asymmetry. 26842584 8 33 theme arrival 1507:1513 arg1 ATD 1534:1536 ATD 1534:1536 ATD 1534:1536 Estimated collisional cross sections were similar to those of the unreduced compounds but with symmetrical arrival time distribution (ATD) profiles, unlike those of the unreduced glycans whose peaks often contained prominent asymmetry. 26842584 6 34 from terminus 1228:1235 arg1 ion 1206:1208 A cleavage ion 1195:1208 the prominent (2,4) A cleavage ion from the reducing terminus 1175:1235 Estimated collisional cross sections were measured with dextran as the calibrant, RESULTS Fragment ions were similar to those from the unreduced glycans with the exception that the prominent (2,4) A cleavage ion from the reducing terminus was replaced by a prominent [M-H3 PO4](-) ion. 26842584 10 35 theme residue 1764:1770 arg1 Reduction 1722:1730 CONCLUSIONS Reduction 1710:1730 CONCLUSIONS Reduction of the reducing terminal GlcNAc residue 1710:1770 CONCLUSIONS Reduction of the reducing terminal GlcNAc residue resulted in fewer diagnostic ions from the chitobiose core but fragmentation of the remainder of the molecules generally paralleled that of the unreduced glycans. 26842584 8 36 theme distribution 1520:1531 arg1 profiles 1539:1546 symmetrical arrival time distribution (ATD) profiles 1495:1546 symmetrical arrival time distribution (ATD) profiles 1495:1546 Estimated collisional cross sections were similar to those of the unreduced compounds but with symmetrical arrival time distribution (ATD) profiles, unlike those of the unreduced glycans whose peaks often contained prominent asymmetry. 26842584 8 36 theme distribution 1520:1531 arg1 ATD 1534:1536 ATD 1534:1536 ATD 1534:1536 Estimated collisional cross sections were similar to those of the unreduced compounds but with symmetrical arrival time distribution (ATD) profiles, unlike those of the unreduced glycans whose peaks often contained prominent asymmetry. 26842584 3 37 theme peaks 455:459 arg1 production 432:441 production 432:441 production of multiple peaks from α- and β-anomers 432:481 For some structural studies, particularly those involving chromatography, glycans are often reduced to avoid production of multiple peaks from α- and β-anomers. 26842584 5 38 theme sodium 759:764 arg1 cyanoborohydride 766:781 sodium cyanoborohydride 759:781 sodium cyanoborohydride 759:781 METHODS Released N-glycans from the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin were reduced with sodium cyanoborohydride and both negative ion CID spectra and ion mobility properties of their phosphate adducts were examined with a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer with electrospray sample introduction. 26842584 10 39 from core 1826:1829 arg1 ions 1801:1804 fewer diagnostic ions 1784:1804 fewer diagnostic ions from the chitobiose core 1784:1829 CONCLUSIONS Reduction of the reducing terminal GlcNAc residue resulted in fewer diagnostic ions from the chitobiose core but fragmentation of the remainder of the molecules generally paralleled that of the unreduced glycans. 26842584 0 40 from properties 31:40 arg1 carbohydrates 73:85 N-linked carbohydrates 64:85 N-linked carbohydrates 64:85 Fragmentation and ion mobility properties of negative ions from N-linked carbohydrates: Part 7. 26842584 8 41 contain contained 1605:1613 arg2 asymmetry 1625:1633 prominent asymmetry 1615:1633 prominent asymmetry 1615:1633 Estimated collisional cross sections were similar to those of the unreduced compounds but with symmetrical arrival time distribution (ATD) profiles, unlike those of the unreduced glycans whose peaks often contained prominent asymmetry. 26842584 8 41 contain contained 1605:1613 arg1 peaks 1593:1597 peaks 1593:1597 peaks 1593:1597 Estimated collisional cross sections were similar to those of the unreduced compounds but with symmetrical arrival time distribution (ATD) profiles, unlike those of the unreduced glycans whose peaks often contained prominent asymmetry. 26842584 5 42 theme mobility 825:832 arg1 properties 834:843 ion mobility properties 821:843 ion mobility properties 821:843 METHODS Released N-glycans from the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin were reduced with sodium cyanoborohydride and both negative ion CID spectra and ion mobility properties of their phosphate adducts were examined with a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer with electrospray sample introduction. 26842584 5 43 theme sample 977:982 arg1 introduction 984:995 electrospray sample introduction 964:995 electrospray sample introduction 964:995 METHODS Released N-glycans from the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin were reduced with sodium cyanoborohydride and both negative ion CID spectra and ion mobility properties of their phosphate adducts were examined with a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer with electrospray sample introduction. 26842584 7 44 theme chitobiose 1312:1321 arg1 core 1323:1326 the chitobiose core 1308:1326 the chitobiose core 1308:1326 Other ions arising from the chitobiose core were of lower relative abundance than those from the unreduced glycans. 26842584 4 45 theme ions 561:564 arg1 production 527:536 the production 523:536 the production of diagnostic fragment ions 523:564 We examined the effect of reduction on the production of diagnostic fragment ions and on the ion mobility properties of N-glycans. 26842584 11 46 theme most 1941:1944 arg1 information 1957:1967 most structural information 1941:1967 most structural information 1941:1967 Thus, most structural information, with the exception of the linkage position of fucose on the core GlcNAc, was available. 26842584 0 47 theme ion 18:20 arg1 properties 31:40 ion mobility properties 18:40 ion mobility properties 18:40 Fragmentation and ion mobility properties of negative ions from N-linked carbohydrates: Part 7. 26842584 11 48 theme position 2004:2011 arg1 exception 1979:1987 the exception 1975:1987 the exception of the linkage position of fucose on the core GlcNAc 1975:2040 Thus, most structural information, with the exception of the linkage position of fucose on the core GlcNAc, was available. 26842584 1 49 theme Reduced 96:102 arg1 glycans 104:110 Reduced glycans 96:110 Reduced glycans. 96:111 Reduced glycans. 26842584 11 50 with available 2047:2055 arg1 exception 1979:1987 the exception 1975:1987 the exception of the linkage position of fucose on the core GlcNAc 1975:2040 Thus, most structural information, with the exception of the linkage position of fucose on the core GlcNAc, was available. 26842584 6 51 theme Fragment 1088:1095 arg1 ions 1097:1100 Fragment ions 1088:1100 RESULTS Fragment ions 1080:1100 Estimated collisional cross sections were measured with dextran as the calibrant, RESULTS Fragment ions were similar to those from the unreduced glycans with the exception that the prominent (2,4) A cleavage ion from the reducing terminus was replaced by a prominent [M-H3 PO4](-) ion. 26842584 5 52 theme CID 805:807 arg1 spectra 809:815 negative ion CID spectra 792:815 negative ion CID spectra 792:815 METHODS Released N-glycans from the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin were reduced with sodium cyanoborohydride and both negative ion CID spectra and ion mobility properties of their phosphate adducts were examined with a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer with electrospray sample introduction. 26842584 2 53 theme CID 168:170 arg1 spectra 173:179 RATIONALE Negative ion collision-induced dissociation (CID) spectra 113:179 RATIONALE Negative ion collision-induced dissociation (CID) spectra of released N-glycans 113:201 RATIONALE Negative ion collision-induced dissociation (CID) spectra of released N-glycans provide very informative structural information relating to branching patterns and location of residues such as fucose. 26842584 8 54 theme Estimated 1400:1408 arg1 sections 1428:1435 Estimated collisional cross sections 1400:1435 Estimated collisional cross sections 1400:1435 Estimated collisional cross sections were similar to those of the unreduced compounds but with symmetrical arrival time distribution (ATD) profiles, unlike those of the unreduced glycans whose peaks often contained prominent asymmetry. 26842584 10 55 theme CONCLUSIONS 1710:1720 arg1 Reduction 1722:1730 CONCLUSIONS Reduction 1710:1730 CONCLUSIONS Reduction of the reducing terminal GlcNAc residue 1710:1770 CONCLUSIONS Reduction of the reducing terminal GlcNAc residue resulted in fewer diagnostic ions from the chitobiose core but fragmentation of the remainder of the molecules generally paralleled that of the unreduced glycans. 26842584 0 56 theme negative 45:52 arg1 ions 54:57 negative ions 45:57 negative ions from N-linked carbohydrates 45:85 Fragmentation and ion mobility properties of negative ions from N-linked carbohydrates: Part 7. 26842584 8 57 theme symmetrical 1495:1505 arg1 profiles 1539:1546 symmetrical arrival time distribution (ATD) profiles 1495:1546 symmetrical arrival time distribution (ATD) profiles 1495:1546 Estimated collisional cross sections were similar to those of the unreduced compounds but with symmetrical arrival time distribution (ATD) profiles, unlike those of the unreduced glycans whose peaks often contained prominent asymmetry. 26842584 8 57 theme symmetrical 1495:1505 arg1 ATD 1534:1536 ATD 1534:1536 ATD 1534:1536 Estimated collisional cross sections were similar to those of the unreduced compounds but with symmetrical arrival time distribution (ATD) profiles, unlike those of the unreduced glycans whose peaks often contained prominent asymmetry. 26842584 0 58 link N-linked 64:71 arg1 carbohydrates 73:85 N-linked carbohydrates 64:85 N-linked carbohydrates 64:85 Fragmentation and ion mobility properties of negative ions from N-linked carbohydrates: Part 7. 26842584 8 59 theme unreduced 1569:1577 arg1 glycans 1579:1585 the unreduced glycans 1565:1585 the unreduced glycans whose peaks often contained prominent asymmetry 1565:1633 Estimated collisional cross sections were similar to those of the unreduced compounds but with symmetrical arrival time distribution (ATD) profiles, unlike those of the unreduced glycans whose peaks often contained prominent asymmetry. 26842584 4 60 theme diagnostic 541:550 arg1 ions 561:564 diagnostic fragment ions 541:564 diagnostic fragment ions 541:564 We examined the effect of reduction on the production of diagnostic fragment ions and on the ion mobility properties of N-glycans. 26842584 8 61 theme cross 1422:1426 arg1 sections 1428:1435 Estimated collisional cross sections 1400:1435 Estimated collisional cross sections 1400:1435 Estimated collisional cross sections were similar to those of the unreduced compounds but with symmetrical arrival time distribution (ATD) profiles, unlike those of the unreduced glycans whose peaks often contained prominent asymmetry. 26842584 11 62 from GlcNAc 2035:2040 arg1 exception 1979:1987 the exception 1975:1987 the exception of the linkage position of fucose on the core GlcNAc 1975:2040 Thus, most structural information, with the exception of the linkage position of fucose on the core GlcNAc, was available. 26842584 4 63 theme N-glycans 604:612 arg1 properties 590:599 the ion mobility properties 573:599 the ion mobility properties of N-glycans 573:612 We examined the effect of reduction on the production of diagnostic fragment ions and on the ion mobility properties of N-glycans. 26842584 2 64 theme released 184:191 arg1 N-glycans 193:201 released N-glycans 184:201 released N-glycans 184:201 RATIONALE Negative ion collision-induced dissociation (CID) spectra of released N-glycans provide very informative structural information relating to branching patterns and location of residues such as fucose. 26842584 10 65 theme reducing 1739:1746 arg1 residue 1764:1770 the reducing terminal GlcNAc residue 1735:1770 the reducing terminal GlcNAc residue 1735:1770 CONCLUSIONS Reduction of the reducing terminal GlcNAc residue resulted in fewer diagnostic ions from the chitobiose core but fragmentation of the remainder of the molecules generally paralleled that of the unreduced glycans. 26842584 0 66 dep Fragmentation 0:12 arg1 Part 88:91 Part 7 88:93 Fragmentation and ion mobility properties of negative ions from N-linked carbohydrates: Part 7. 0:94 Fragmentation and ion mobility properties of negative ions from N-linked carbohydrates: Part 7. 26842584 11 67 from position 2004:2011 arg1 GlcNAc 2035:2040 the core GlcNAc 2026:2040 the core GlcNAc 2026:2040 Thus, most structural information, with the exception of the linkage position of fucose on the core GlcNAc, was available. 26842584 2 68 theme RATIONALE 113:121 arg1 spectra 173:179 RATIONALE Negative ion collision-induced dissociation (CID) spectra 113:179 RATIONALE Negative ion collision-induced dissociation (CID) spectra of released N-glycans 113:201 RATIONALE Negative ion collision-induced dissociation (CID) spectra of released N-glycans provide very informative structural information relating to branching patterns and location of residues such as fucose. 26842584 5 69 theme bovine 665:670 arg1 fetuin 672:677 bovine fetuin 665:677 bovine fetuin 665:677 METHODS Released N-glycans from the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin were reduced with sodium cyanoborohydride and both negative ion CID spectra and ion mobility properties of their phosphate adducts were examined with a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer with electrospray sample introduction. 26842584 5 69 theme bovine 665:670 arg1 glycoproteins 651:663 the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin 647:739 the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin 647:739 METHODS Released N-glycans from the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin were reduced with sodium cyanoborohydride and both negative ion CID spectra and ion mobility properties of their phosphate adducts were examined with a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer with electrospray sample introduction. 26842584 10 70 theme remainder 1856:1864 arg1 fragmentation 1835:1847 fragmentation 1835:1847 fragmentation of the remainder of the molecules 1835:1881 CONCLUSIONS Reduction of the reducing terminal GlcNAc residue resulted in fewer diagnostic ions from the chitobiose core but fragmentation of the remainder of the molecules generally paralleled that of the unreduced glycans. 26842584 4 71 theme ion 577:579 arg1 properties 590:599 the ion mobility properties 573:599 the ion mobility properties of N-glycans 573:612 We examined the effect of reduction on the production of diagnostic fragment ions and on the ion mobility properties of N-glycans. 26842584 12 72 theme non-reduced 2187:2197 arg1 compounds 2199:2207 the non-reduced compounds 2183:2207 the non-reduced compounds 2183:2207 ATD peaks were symmetrical with the result that cross sections were more appropriate for data-base searching than those from the non-reduced compounds where asymmetry produced lower precision in the measurement. 26842584 11 73 theme fucose 2016:2021 arg1 position 2004:2011 the linkage position 1992:2011 the linkage position of fucose on the core GlcNAc 1992:2040 Thus, most structural information, with the exception of the linkage position of fucose on the core GlcNAc, was available. 26842584 11 74 from exception 1979:1987 arg1 GlcNAc 2035:2040 the core GlcNAc 2026:2040 the core GlcNAc 2026:2040 Thus, most structural information, with the exception of the linkage position of fucose on the core GlcNAc, was available. 26842584 2 75 theme dissociation 154:165 arg1 spectra 173:179 RATIONALE Negative ion collision-induced dissociation (CID) spectra 113:179 RATIONALE Negative ion collision-induced dissociation (CID) spectra of released N-glycans 113:201 RATIONALE Negative ion collision-induced dissociation (CID) spectra of released N-glycans provide very informative structural information relating to branching patterns and location of residues such as fucose. 26842584 4 76 from effect 500:505 arg1 properties 590:599 the ion mobility properties 573:599 the ion mobility properties of N-glycans 573:612 We examined the effect of reduction on the production of diagnostic fragment ions and on the ion mobility properties of N-glycans. 26842584 4 76 from effect 500:505 arg1 production 527:536 the production 523:536 the production of diagnostic fragment ions 523:564 We examined the effect of reduction on the production of diagnostic fragment ions and on the ion mobility properties of N-glycans. 26842584 10 77 theme GlcNAc 1757:1762 arg1 residue 1764:1770 the reducing terminal GlcNAc residue 1735:1770 the reducing terminal GlcNAc residue 1735:1770 CONCLUSIONS Reduction of the reducing terminal GlcNAc residue resulted in fewer diagnostic ions from the chitobiose core but fragmentation of the remainder of the molecules generally paralleled that of the unreduced glycans. 26842584 2 78 theme ion 132:134 arg1 spectra 173:179 RATIONALE Negative ion collision-induced dissociation (CID) spectra 113:179 RATIONALE Negative ion collision-induced dissociation (CID) spectra of released N-glycans 113:201 RATIONALE Negative ion collision-induced dissociation (CID) spectra of released N-glycans provide very informative structural information relating to branching patterns and location of residues such as fucose. 26842584 5 79 attach Released 623:630 arg2 METHODS 615:621 METHODS 615:621 METHODS Released N-glycans from the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin 615:739 METHODS Released N-glycans from the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin were reduced with sodium cyanoborohydride and both negative ion CID spectra and ion mobility properties of their phosphate adducts were examined with a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer with electrospray sample introduction. 26842584 5 79 attach Released 623:630 arg1 thyroglobulin 727:739 porcine thyroglobulin 719:739 porcine thyroglobulin 719:739 METHODS Released N-glycans from the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin were reduced with sodium cyanoborohydride and both negative ion CID spectra and ion mobility properties of their phosphate adducts were examined with a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer with electrospray sample introduction. 26842584 5 79 attach Released 623:630 arg1 B 693:693 ribonuclease B 680:693 ribonuclease B 680:693 METHODS Released N-glycans from the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin were reduced with sodium cyanoborohydride and both negative ion CID spectra and ion mobility properties of their phosphate adducts were examined with a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer with electrospray sample introduction. 26842584 5 79 attach Released 623:630 arg1 glycoproteins 651:663 the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin 647:739 the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin 647:739 METHODS Released N-glycans from the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin were reduced with sodium cyanoborohydride and both negative ion CID spectra and ion mobility properties of their phosphate adducts were examined with a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer with electrospray sample introduction. 26842584 5 79 attach Released 623:630 arg1 ovalbumin 704:712 chicken ovalbumin 696:712 chicken ovalbumin 696:712 METHODS Released N-glycans from the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin were reduced with sodium cyanoborohydride and both negative ion CID spectra and ion mobility properties of their phosphate adducts were examined with a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer with electrospray sample introduction. 26842584 5 79 attach Released 623:630 arg1 fetuin 672:677 bovine fetuin 665:677 bovine fetuin 665:677 METHODS Released N-glycans from the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin were reduced with sodium cyanoborohydride and both negative ion CID spectra and ion mobility properties of their phosphate adducts were examined with a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer with electrospray sample introduction. 26842584 10 80 theme fewer 1784:1788 arg1 ions 1801:1804 fewer diagnostic ions 1784:1804 fewer diagnostic ions from the chitobiose core 1784:1829 CONCLUSIONS Reduction of the reducing terminal GlcNAc residue resulted in fewer diagnostic ions from the chitobiose core but fragmentation of the remainder of the molecules generally paralleled that of the unreduced glycans. 26842584 6 81 theme collisional 1008:1018 arg1 calibrant 1069:1077 the calibrant 1065:1077 the calibrant 1065:1077 Estimated collisional cross sections were measured with dextran as the calibrant, RESULTS Fragment ions were similar to those from the unreduced glycans with the exception that the prominent (2,4) A cleavage ion from the reducing terminus was replaced by a prominent [M-H3 PO4](-) ion. 26842584 6 81 theme collisional 1008:1018 arg1 sections 1026:1033 Estimated collisional cross sections 998:1033 Estimated collisional cross sections 998:1033 Estimated collisional cross sections were measured with dextran as the calibrant, RESULTS Fragment ions were similar to those from the unreduced glycans with the exception that the prominent (2,4) A cleavage ion from the reducing terminus was replaced by a prominent [M-H3 PO4](-) ion. 26842584 6 82 theme prominent 1179:1187 arg1 ion 1206:1208 A cleavage ion 1195:1208 the prominent (2,4) A cleavage ion from the reducing terminus 1175:1235 Estimated collisional cross sections were measured with dextran as the calibrant, RESULTS Fragment ions were similar to those from the unreduced glycans with the exception that the prominent (2,4) A cleavage ion from the reducing terminus was replaced by a prominent [M-H3 PO4](-) ion. 26842584 5 83 theme porcine 719:725 arg1 glycoproteins 651:663 the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin 647:739 the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin 647:739 METHODS Released N-glycans from the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin were reduced with sodium cyanoborohydride and both negative ion CID spectra and ion mobility properties of their phosphate adducts were examined with a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer with electrospray sample introduction. 26842584 5 83 theme porcine 719:725 arg1 thyroglobulin 727:739 porcine thyroglobulin 719:739 porcine thyroglobulin 719:739 METHODS Released N-glycans from the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin were reduced with sodium cyanoborohydride and both negative ion CID spectra and ion mobility properties of their phosphate adducts were examined with a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer with electrospray sample introduction. 26842584 5 84 theme adducts 864:870 arg1 spectra 809:815 negative ion CID spectra 792:815 negative ion CID spectra 792:815 METHODS Released N-glycans from the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin were reduced with sodium cyanoborohydride and both negative ion CID spectra and ion mobility properties of their phosphate adducts were examined with a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer with electrospray sample introduction. 26842584 5 84 theme adducts 864:870 arg1 properties 834:843 ion mobility properties 821:843 ion mobility properties 821:843 METHODS Released N-glycans from the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin were reduced with sodium cyanoborohydride and both negative ion CID spectra and ion mobility properties of their phosphate adducts were examined with a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer with electrospray sample introduction. 26842584 6 85 dep ion 1206:1208 arg1 2,4 1190:1192 2,4 1190:1192 2,4 1190:1192 Estimated collisional cross sections were measured with dextran as the calibrant, RESULTS Fragment ions were similar to those from the unreduced glycans with the exception that the prominent (2,4) A cleavage ion from the reducing terminus was replaced by a prominent [M-H3 PO4](-) ion. 26842584 2 86 theme structural 228:237 arg1 information 239:249 very informative structural information 211:249 very informative structural information relating to branching patterns and location of residues such as fucose 211:320 RATIONALE Negative ion collision-induced dissociation (CID) spectra of released N-glycans provide very informative structural information relating to branching patterns and location of residues such as fucose. 26842584 5 87 theme mobility 932:939 arg1 spectrometer 946:957 a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer 891:957 a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer 891:957 METHODS Released N-glycans from the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin were reduced with sodium cyanoborohydride and both negative ion CID spectra and ion mobility properties of their phosphate adducts were examined with a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer with electrospray sample introduction. 26842584 0 88 from Fragmentation 0:12 arg1 carbohydrates 73:85 N-linked carbohydrates 64:85 N-linked carbohydrates 64:85 Fragmentation and ion mobility properties of negative ions from N-linked carbohydrates: Part 7. 26842584 8 89 theme unreduced 1466:1474 arg1 compounds 1476:1484 the unreduced compounds 1462:1484 the unreduced compounds 1462:1484 Estimated collisional cross sections were similar to those of the unreduced compounds but with symmetrical arrival time distribution (ATD) profiles, unlike those of the unreduced glycans whose peaks often contained prominent asymmetry. 26842584 5 90 theme chicken 696:702 arg1 ovalbumin 704:712 chicken ovalbumin 696:712 chicken ovalbumin 696:712 METHODS Released N-glycans from the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin were reduced with sodium cyanoborohydride and both negative ion CID spectra and ion mobility properties of their phosphate adducts were examined with a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer with electrospray sample introduction. 26842584 5 90 theme chicken 696:702 arg1 glycoproteins 651:663 the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin 647:739 the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin 647:739 METHODS Released N-glycans from the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin were reduced with sodium cyanoborohydride and both negative ion CID spectra and ion mobility properties of their phosphate adducts were examined with a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer with electrospray sample introduction. 26842584 12 91 theme data-base 2147:2155 arg1 searching 2157:2165 data-base searching 2147:2165 data-base searching 2147:2165 ATD peaks were symmetrical with the result that cross sections were more appropriate for data-base searching than those from the non-reduced compounds where asymmetry produced lower precision in the measurement. 26842584 0 92 theme N-linked 64:71 arg1 carbohydrates 73:85 N-linked carbohydrates 64:85 N-linked carbohydrates 64:85 Fragmentation and ion mobility properties of negative ions from N-linked carbohydrates: Part 7. 26842584 2 93 theme branching 263:271 arg1 patterns 273:280 branching patterns 263:280 branching patterns 263:280 RATIONALE Negative ion collision-induced dissociation (CID) spectra of released N-glycans provide very informative structural information relating to branching patterns and location of residues such as fucose. 26842584 5 94 theme Synapt 900:905 arg1 spectrometer 946:957 a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer 891:957 a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer 891:957 METHODS Released N-glycans from the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin were reduced with sodium cyanoborohydride and both negative ion CID spectra and ion mobility properties of their phosphate adducts were examined with a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer with electrospray sample introduction. 26842584 4 95 theme reduction 510:518 arg1 effect 500:505 the effect 496:505 the effect of reduction on the production of diagnostic fragment ions and on the ion mobility properties of N-glycans 496:612 We examined the effect of reduction on the production of diagnostic fragment ions and on the ion mobility properties of N-glycans. 26842584 5 96 theme travelling-wave 912:926 arg1 spectrometer 946:957 a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer 891:957 a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer 891:957 METHODS Released N-glycans from the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin were reduced with sodium cyanoborohydride and both negative ion CID spectra and ion mobility properties of their phosphate adducts were examined with a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer with electrospray sample introduction. 26842584 3 97 theme structural 332:341 arg1 studies 343:349 some structural studies 327:349 some structural studies 327:349 For some structural studies, particularly those involving chromatography, glycans are often reduced to avoid production of multiple peaks from α- and β-anomers. 26842584 3 97 theme structural 332:341 arg1 those 365:369 those 365:369 those 365:369 For some structural studies, particularly those involving chromatography, glycans are often reduced to avoid production of multiple peaks from α- and β-anomers. 26842584 8 98 theme time 1515:1518 arg1 profiles 1539:1546 symmetrical arrival time distribution (ATD) profiles 1495:1546 symmetrical arrival time distribution (ATD) profiles 1495:1546 Estimated collisional cross sections were similar to those of the unreduced compounds but with symmetrical arrival time distribution (ATD) profiles, unlike those of the unreduced glycans whose peaks often contained prominent asymmetry. 26842584 8 98 theme time 1515:1518 arg1 ATD 1534:1536 ATD 1534:1536 ATD 1534:1536 Estimated collisional cross sections were similar to those of the unreduced compounds but with symmetrical arrival time distribution (ATD) profiles, unlike those of the unreduced glycans whose peaks often contained prominent asymmetry. 26842584 3 99 from production 432:441 arg1 β-anomers 473:481 β-anomers 473:481 β-anomers 473:481 For some structural studies, particularly those involving chromatography, glycans are often reduced to avoid production of multiple peaks from α- and β-anomers. 26842584 3 99 from production 432:441 arg1 α- 466:467 α- 466:467 α- 466:467 For some structural studies, particularly those involving chromatography, glycans are often reduced to avoid production of multiple peaks from α- and β-anomers. 26842584 12 100 theme lower 2234:2238 arg1 precision 2240:2248 lower precision 2234:2248 lower precision 2234:2248 ATD peaks were symmetrical with the result that cross sections were more appropriate for data-base searching than those from the non-reduced compounds where asymmetry produced lower precision in the measurement. 26842584 6 101 dep RESULTS 1080:1086 arg1 ions 1097:1100 Fragment ions 1088:1100 RESULTS Fragment ions 1080:1100 Estimated collisional cross sections were measured with dextran as the calibrant, RESULTS Fragment ions were similar to those from the unreduced glycans with the exception that the prominent (2,4) A cleavage ion from the reducing terminus was replaced by a prominent [M-H3 PO4](-) ion. 26842584 5 102 theme ion 821:823 arg1 properties 834:843 ion mobility properties 821:843 ion mobility properties 821:843 METHODS Released N-glycans from the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin were reduced with sodium cyanoborohydride and both negative ion CID spectra and ion mobility properties of their phosphate adducts were examined with a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer with electrospray sample introduction. 26842584 5 103 theme electrospray 964:975 arg1 introduction 984:995 electrospray sample introduction 964:995 electrospray sample introduction 964:995 METHODS Released N-glycans from the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin were reduced with sodium cyanoborohydride and both negative ion CID spectra and ion mobility properties of their phosphate adducts were examined with a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer with electrospray sample introduction. 26842584 3 104 theme multiple 446:453 arg1 peaks 455:459 multiple peaks 446:459 multiple peaks from α- and β-anomers 446:481 For some structural studies, particularly those involving chromatography, glycans are often reduced to avoid production of multiple peaks from α- and β-anomers. 26842584 0 105 theme mobility 22:29 arg1 properties 31:40 ion mobility properties 18:40 ion mobility properties 18:40 Fragmentation and ion mobility properties of negative ions from N-linked carbohydrates: Part 7. 26842584 10 106 theme molecules 1873:1881 arg1 remainder 1856:1864 the remainder 1852:1864 the remainder of the molecules 1852:1881 CONCLUSIONS Reduction of the reducing terminal GlcNAc residue resulted in fewer diagnostic ions from the chitobiose core but fragmentation of the remainder of the molecules generally paralleled that of the unreduced glycans. 26842584 11 107 theme structural 1946:1955 arg1 information 1957:1967 most structural information 1941:1967 most structural information 1941:1967 Thus, most structural information, with the exception of the linkage position of fucose on the core GlcNAc, was available. 26842584 5 108 theme ion 801:803 arg1 spectra 809:815 negative ion CID spectra 792:815 negative ion CID spectra 792:815 METHODS Released N-glycans from the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin were reduced with sodium cyanoborohydride and both negative ion CID spectra and ion mobility properties of their phosphate adducts were examined with a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer with electrospray sample introduction. 26842584 12 109 theme cross 2106:2110 arg1 sections 2112:2119 cross sections 2106:2119 cross sections 2106:2119 ATD peaks were symmetrical with the result that cross sections were more appropriate for data-base searching than those from the non-reduced compounds where asymmetry produced lower precision in the measurement. 26842584 7 110 theme Other 1284:1288 arg1 ions 1290:1293 Other ions 1284:1293 Other ions arising from the chitobiose core 1284:1326 Other ions arising from the chitobiose core were of lower relative abundance than those from the unreduced glycans. 26842584 5 111 dep glycoproteins 651:663 arg1 fetuin 672:677 bovine fetuin 665:677 bovine fetuin 665:677 METHODS Released N-glycans from the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin were reduced with sodium cyanoborohydride and both negative ion CID spectra and ion mobility properties of their phosphate adducts were examined with a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer with electrospray sample introduction. 26842584 5 111 dep glycoproteins 651:663 arg1 B 693:693 ribonuclease B 680:693 ribonuclease B 680:693 METHODS Released N-glycans from the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin were reduced with sodium cyanoborohydride and both negative ion CID spectra and ion mobility properties of their phosphate adducts were examined with a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer with electrospray sample introduction. 26842584 5 111 dep glycoproteins 651:663 arg1 ovalbumin 704:712 chicken ovalbumin 696:712 chicken ovalbumin 696:712 METHODS Released N-glycans from the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin were reduced with sodium cyanoborohydride and both negative ion CID spectra and ion mobility properties of their phosphate adducts were examined with a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer with electrospray sample introduction. 26842584 5 111 dep glycoproteins 651:663 arg1 glycoproteins 651:663 the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin 647:739 the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin 647:739 METHODS Released N-glycans from the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin were reduced with sodium cyanoborohydride and both negative ion CID spectra and ion mobility properties of their phosphate adducts were examined with a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer with electrospray sample introduction. 26842584 5 111 dep glycoproteins 651:663 arg1 thyroglobulin 727:739 porcine thyroglobulin 719:739 porcine thyroglobulin 719:739 METHODS Released N-glycans from the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin were reduced with sodium cyanoborohydride and both negative ion CID spectra and ion mobility properties of their phosphate adducts were examined with a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer with electrospray sample introduction. 26842584 3 112 from α- 466:467 arg1 peaks 455:459 multiple peaks 446:459 multiple peaks from α- and β-anomers 446:481 For some structural studies, particularly those involving chromatography, glycans are often reduced to avoid production of multiple peaks from α- and β-anomers. 26842584 3 112 from α- 466:467 arg1 production 432:441 production 432:441 production of multiple peaks from α- and β-anomers 432:481 For some structural studies, particularly those involving chromatography, glycans are often reduced to avoid production of multiple peaks from α- and β-anomers. 26842584 0 113 theme ions 54:57 arg1 Fragmentation 0:12 Fragmentation 0:12 Fragmentation 0:12 Fragmentation and ion mobility properties of negative ions from N-linked carbohydrates: Part 7. 26842584 0 113 theme ions 54:57 arg1 properties 31:40 ion mobility properties 18:40 ion mobility properties 18:40 Fragmentation and ion mobility properties of negative ions from N-linked carbohydrates: Part 7. 26842584 4 114 theme fragment 552:559 arg1 ions 561:564 diagnostic fragment ions 541:564 diagnostic fragment ions 541:564 We examined the effect of reduction on the production of diagnostic fragment ions and on the ion mobility properties of N-glycans. 26842584 3 115 from β-anomers 473:481 arg1 peaks 455:459 multiple peaks 446:459 multiple peaks from α- and β-anomers 446:481 For some structural studies, particularly those involving chromatography, glycans are often reduced to avoid production of multiple peaks from α- and β-anomers. 26842584 3 115 from β-anomers 473:481 arg1 production 432:441 production 432:441 production of multiple peaks from α- and β-anomers 432:481 For some structural studies, particularly those involving chromatography, glycans are often reduced to avoid production of multiple peaks from α- and β-anomers. 26842584 2 116 theme N-glycans 193:201 arg1 spectra 173:179 RATIONALE Negative ion collision-induced dissociation (CID) spectra 113:179 RATIONALE Negative ion collision-induced dissociation (CID) spectra of released N-glycans 113:201 RATIONALE Negative ion collision-induced dissociation (CID) spectra of released N-glycans provide very informative structural information relating to branching patterns and location of residues such as fucose. 26842584 8 117 theme collisional 1410:1420 arg1 sections 1428:1435 Estimated collisional cross sections 1400:1435 Estimated collisional cross sections 1400:1435 Estimated collisional cross sections were similar to those of the unreduced compounds but with symmetrical arrival time distribution (ATD) profiles, unlike those of the unreduced glycans whose peaks often contained prominent asymmetry. 26842584 2 118 theme Negative 123:130 arg1 spectra 173:179 RATIONALE Negative ion collision-induced dissociation (CID) spectra 113:179 RATIONALE Negative ion collision-induced dissociation (CID) spectra of released N-glycans 113:201 RATIONALE Negative ion collision-induced dissociation (CID) spectra of released N-glycans provide very informative structural information relating to branching patterns and location of residues such as fucose. 26745591 8 0 contain have 1123:1126 arg1 N-glycosylation 1071:1085 N-glycosylation 1071:1085 N-glycosylation on specific asparagine residues 1071:1117 In contrast, N-glycosylation on specific asparagine residues may have an essential role in the conducting function of the channel by enhancing the channel permeability and / or the pore opening of the channel. 26745591 8 0 contain have 1123:1126 arg2 role 1141:1144 an essential role 1128:1144 an essential role 1128:1144 In contrast, N-glycosylation on specific asparagine residues may have an essential role in the conducting function of the channel by enhancing the channel permeability and / or the pore opening of the channel. 26745591 4 1 theme signaling 558:566 arg1 pathway 568:574 an essential signaling pathway 545:574 an essential signaling pathway by which the cellular environment can control expression of T-type channels 545:650 Asparagine-linked glycosylation has recently emerged as an essential signaling pathway by which the cellular environment can control expression of T-type channels. 26745591 8 2 from N-glycosylation 1071:1085 arg1 residues 1110:1117 specific asparagine residues 1090:1117 specific asparagine residues 1090:1117 In contrast, N-glycosylation on specific asparagine residues may have an essential role in the conducting function of the channel by enhancing the channel permeability and / or the pore opening of the channel. 26745591 9 3 link N-linked 1304:1311 arg1 glycosylation 1313:1325 N-linked glycosylation 1304:1325 N-linked glycosylation of hCav3.2 channels 1304:1345 Our data suggest that modulation of N-linked glycosylation of hCav3.2 channels may play an important physiological role, and could also support the alteration of T-type currents observed in disease states. 26745591 9 4 gly glycosylation 1313:1325 arg1 channels 1338:1345 hCav3.2 channels 1330:1345 hCav3.2 channels 1330:1345 Our data suggest that modulation of N-linked glycosylation of hCav3.2 channels may play an important physiological role, and could also support the alteration of T-type currents observed in disease states. 26745591 8 5 theme channel 1259:1265 arg1 permeability 1213:1224 the channel permeability and / or the pore opening 1201:1250 permeability 1213:1224 In contrast, N-glycosylation on specific asparagine residues may have an essential role in the conducting function of the channel by enhancing the channel permeability and / or the pore opening of the channel. 26745591 8 5 theme channel 1259:1265 arg1 opening 1244:1250 the pore opening 1235:1250 the pore opening 1235:1250 In contrast, N-glycosylation on specific asparagine residues may have an essential role in the conducting function of the channel by enhancing the channel permeability and / or the pore opening of the channel. 26745591 5 6 theme T-type 714:719 arg1 channels 721:728 T-type channels 714:728 T-type channels 714:728 However, the role of N-glycans in the conducting function of T-type channels remains elusive. 26745591 5 7 from role 666:669 arg1 function 702:709 the conducting function 687:709 the conducting function of T-type channels 687:728 However, the role of N-glycans in the conducting function of T-type channels remains elusive. 26745591 4 8 theme channels 643:650 arg1 expression 622:631 expression 622:631 expression of T-type channels 622:650 Asparagine-linked glycosylation has recently emerged as an essential signaling pathway by which the cellular environment can control expression of T-type channels. 26745591 9 9 theme important 1359:1367 arg1 role 1383:1386 an important physiological role 1356:1386 an important physiological role 1356:1386 Our data suggest that modulation of N-linked glycosylation of hCav3.2 channels may play an important physiological role, and could also support the alteration of T-type currents observed in disease states. 26745591 5 10 theme channels 721:728 arg1 function 702:709 the conducting function 687:709 the conducting function of T-type channels 687:728 However, the role of N-glycans in the conducting function of T-type channels remains elusive. 26745591 7 11 theme channel 1034:1040 arg1 voltage-sensor 1042:1055 the channel voltage-sensor 1030:1055 the channel voltage-sensor 1030:1055 Patch-clamp recordings of gating currents revealed that N-glycans attached to hCav3.2 channels have a minimal effect on the functioning of the channel voltage-sensor. 26745591 7 12 attach attached 957:964 arg1 channels 977:984 hCav3.2 channels 969:984 hCav3.2 channels 969:984 Patch-clamp recordings of gating currents revealed that N-glycans attached to hCav3.2 channels have a minimal effect on the functioning of the channel voltage-sensor. 26745591 7 12 attach attached 957:964 arg2 N-glycans 947:955 N-glycans 947:955 N-glycans attached to hCav3.2 channels 947:984 Patch-clamp recordings of gating currents revealed that N-glycans attached to hCav3.2 channels have a minimal effect on the functioning of the channel voltage-sensor. 26745591 9 13 theme physiological 1369:1381 arg1 role 1383:1386 an important physiological role 1356:1386 an important physiological role 1356:1386 Our data suggest that modulation of N-linked glycosylation of hCav3.2 channels may play an important physiological role, and could also support the alteration of T-type currents observed in disease states. 26745591 2 14 theme neuronal 312:319 arg1 epilepsy 362:369 epilepsy 362:369 epilepsy 362:369 Defects in T-type channel expression have been linked to various neuronal disorders including neuropathic pain and epilepsy. 26745591 2 14 theme neuronal 312:319 arg1 disorders 321:329 various neuronal disorders 304:329 various neuronal disorders including neuropathic pain and epilepsy 304:369 Defects in T-type channel expression have been linked to various neuronal disorders including neuropathic pain and epilepsy. 26745591 2 14 theme neuronal 312:319 arg1 pain 353:356 neuropathic pain 341:356 neuropathic pain 341:356 Defects in T-type channel expression have been linked to various neuronal disorders including neuropathic pain and epilepsy. 26745591 7 15 theme currents 924:931 arg1 recordings 903:912 Patch-clamp recordings 891:912 Patch-clamp recordings of gating currents 891:931 Patch-clamp recordings of gating currents revealed that N-glycans attached to hCav3.2 channels have a minimal effect on the functioning of the channel voltage-sensor. 26745591 7 16 theme gating 917:922 arg1 currents 924:931 gating currents 917:931 gating currents 917:931 Patch-clamp recordings of gating currents revealed that N-glycans attached to hCav3.2 channels have a minimal effect on the functioning of the channel voltage-sensor. 26745591 8 17 theme pore 1239:1242 arg1 opening 1244:1250 the pore opening 1235:1250 the pore opening 1235:1250 In contrast, N-glycosylation on specific asparagine residues may have an essential role in the conducting function of the channel by enhancing the channel permeability and / or the pore opening of the channel. 26745591 9 18 theme disease 1458:1464 arg1 states 1466:1471 disease states 1458:1471 disease states 1458:1471 Our data suggest that modulation of N-linked glycosylation of hCav3.2 channels may play an important physiological role, and could also support the alteration of T-type currents observed in disease states. 26745591 8 19 theme essential 1131:1139 arg1 role 1141:1144 an essential role 1128:1144 an essential role 1128:1144 In contrast, N-glycosylation on specific asparagine residues may have an essential role in the conducting function of the channel by enhancing the channel permeability and / or the pore opening of the channel. 26745591 5 20 theme N-glycans 674:682 arg1 role 666:669 the role 662:669 the role of N-glycans in the conducting function of T-type channels 662:728 However, the role of N-glycans in the conducting function of T-type channels remains elusive. 26745591 2 21 theme various 304:310 arg1 epilepsy 362:369 epilepsy 362:369 epilepsy 362:369 Defects in T-type channel expression have been linked to various neuronal disorders including neuropathic pain and epilepsy. 26745591 2 21 theme various 304:310 arg1 disorders 321:329 various neuronal disorders 304:329 various neuronal disorders including neuropathic pain and epilepsy 304:369 Defects in T-type channel expression have been linked to various neuronal disorders including neuropathic pain and epilepsy. 26745591 2 21 theme various 304:310 arg1 pain 353:356 neuropathic pain 341:356 neuropathic pain 341:356 Defects in T-type channel expression have been linked to various neuronal disorders including neuropathic pain and epilepsy. 26745591 2 22 from Defects 247:253 arg1 expression 273:282 T-type channel expression 258:282 T-type channel expression 258:282 Defects in T-type channel expression have been linked to various neuronal disorders including neuropathic pain and epilepsy. 26745591 3 23 theme channels 479:486 arg1 expression 445:454 expression 445:454 expression 445:454 Currently, little is known about the cellular mechanisms controlling the expression and function of T-type channels. 26745591 3 23 theme channels 479:486 arg1 function 460:467 function 460:467 function 460:467 Currently, little is known about the cellular mechanisms controlling the expression and function of T-type channels. 26745591 4 24 theme essential 548:556 arg1 pathway 568:574 an essential signaling pathway 545:574 an essential signaling pathway by which the cellular environment can control expression of T-type channels 545:650 Asparagine-linked glycosylation has recently emerged as an essential signaling pathway by which the cellular environment can control expression of T-type channels. 26745591 3 25 dep expression 445:454 arg1 the 441:443 the 441:443 the 441:443 Currently, little is known about the cellular mechanisms controlling the expression and function of T-type channels. 26745591 1 26 theme Low-voltage-gated 93:109 arg1 channels 126:133 Low-voltage-gated T-type calcium channels 93:133 Low-voltage-gated T-type calcium channels 93:133 Low-voltage-gated T-type calcium channels are expressed throughout the nervous system where they play an essential role in shaping neuronal excitability. 26745591 1 27 theme essential 198:206 arg1 role 208:211 an essential role 195:211 an essential role 195:211 Low-voltage-gated T-type calcium channels are expressed throughout the nervous system where they play an essential role in shaping neuronal excitability. 26745591 9 28 theme channels 1338:1345 arg1 glycosylation 1313:1325 N-linked glycosylation 1304:1325 N-linked glycosylation of hCav3.2 channels 1304:1345 Our data suggest that modulation of N-linked glycosylation of hCav3.2 channels may play an important physiological role, and could also support the alteration of T-type currents observed in disease states. 26745591 5 29 theme conducting 691:700 arg1 function 702:709 the conducting function 687:709 the conducting function of T-type channels 687:728 However, the role of N-glycans in the conducting function of T-type channels remains elusive. 26745591 6 30 theme N-glycosylation 845:859 arg1 role 837:840 the role 833:840 the role of N-glycosylation on the gating of the channel 833:888 In the present study, we used human Cav3.2 glycosylation-deficient channels to assess the role of N-glycosylation on the gating of the channel. 26745591 1 31 theme T-type 111:116 arg1 channels 126:133 Low-voltage-gated T-type calcium channels 93:133 Low-voltage-gated T-type calcium channels 93:133 Low-voltage-gated T-type calcium channels are expressed throughout the nervous system where they play an essential role in shaping neuronal excitability. 26745591 6 32 theme present 754:760 arg1 study 762:766 the present study 750:766 the present study 750:766 In the present study, we used human Cav3.2 glycosylation-deficient channels to assess the role of N-glycosylation on the gating of the channel. 26745591 9 33 located observed 1446:1453 arg2 currents 1437:1444 T-type currents 1430:1444 T-type currents observed in disease states 1430:1471 Our data suggest that modulation of N-linked glycosylation of hCav3.2 channels may play an important physiological role, and could also support the alteration of T-type currents observed in disease states. 26745591 9 33 located observed 1446:1453 arg1 states 1466:1471 disease states 1458:1471 disease states 1458:1471 Our data suggest that modulation of N-linked glycosylation of hCav3.2 channels may play an important physiological role, and could also support the alteration of T-type currents observed in disease states. 26745591 7 34 contain have 986:989 arg1 N-glycans 947:955 N-glycans 947:955 N-glycans attached to hCav3.2 channels 947:984 Patch-clamp recordings of gating currents revealed that N-glycans attached to hCav3.2 channels have a minimal effect on the functioning of the channel voltage-sensor. 26745591 7 34 contain have 986:989 arg2 effect 1001:1006 a minimal effect 991:1006 a minimal effect 991:1006 Patch-clamp recordings of gating currents revealed that N-glycans attached to hCav3.2 channels have a minimal effect on the functioning of the channel voltage-sensor. 26745591 7 35 theme minimal 993:999 arg1 effect 1001:1006 a minimal effect 991:1006 a minimal effect 991:1006 Patch-clamp recordings of gating currents revealed that N-glycans attached to hCav3.2 channels have a minimal effect on the functioning of the channel voltage-sensor. 26745591 1 36 theme calcium 118:124 arg1 channels 126:133 Low-voltage-gated T-type calcium channels 93:133 Low-voltage-gated T-type calcium channels 93:133 Low-voltage-gated T-type calcium channels are expressed throughout the nervous system where they play an essential role in shaping neuronal excitability. 26745591 7 37 theme Patch-clamp 891:901 arg1 recordings 903:912 Patch-clamp recordings 891:912 Patch-clamp recordings of gating currents 891:931 Patch-clamp recordings of gating currents revealed that N-glycans attached to hCav3.2 channels have a minimal effect on the functioning of the channel voltage-sensor. 26745591 3 38 theme T-type 472:477 arg1 channels 479:486 T-type channels 472:486 T-type channels 472:486 Currently, little is known about the cellular mechanisms controlling the expression and function of T-type channels. 26745591 0 39 theme T-type 21:26 arg1 permeability 44:55 Cav3.2 T-type calcium channel permeability 14:55 Cav3.2 T-type calcium channel permeability 14:55 Modulation of Cav3.2 T-type calcium channel permeability by asparagine-linked glycosylation. 26745591 8 40 theme specific 1090:1097 arg1 residues 1110:1117 specific asparagine residues 1090:1117 specific asparagine residues 1090:1117 In contrast, N-glycosylation on specific asparagine residues may have an essential role in the conducting function of the channel by enhancing the channel permeability and / or the pore opening of the channel. 26745591 8 41 theme conducting 1153:1162 arg1 function 1164:1171 the conducting function 1149:1171 the conducting function of the channel 1149:1186 In contrast, N-glycosylation on specific asparagine residues may have an essential role in the conducting function of the channel by enhancing the channel permeability and / or the pore opening of the channel. 26745591 2 42 theme neuropathic 341:351 arg1 pain 353:356 neuropathic pain 341:356 neuropathic pain 341:356 Defects in T-type channel expression have been linked to various neuronal disorders including neuropathic pain and epilepsy. 26745591 1 43 theme shaping 216:222 arg1 excitability 233:244 shaping neuronal excitability 216:244 shaping neuronal excitability 216:244 Low-voltage-gated T-type calcium channels are expressed throughout the nervous system where they play an essential role in shaping neuronal excitability. 26745591 0 44 theme Cav3.2 14:19 arg1 permeability 44:55 Cav3.2 T-type calcium channel permeability 14:55 Cav3.2 T-type calcium channel permeability 14:55 Modulation of Cav3.2 T-type calcium channel permeability by asparagine-linked glycosylation. 26745591 4 45 theme T-type 636:641 arg1 channels 643:650 T-type channels 636:650 T-type channels 636:650 Asparagine-linked glycosylation has recently emerged as an essential signaling pathway by which the cellular environment can control expression of T-type channels. 26745591 1 46 theme neuronal 224:231 arg1 excitability 233:244 shaping neuronal excitability 216:244 shaping neuronal excitability 216:244 Low-voltage-gated T-type calcium channels are expressed throughout the nervous system where they play an essential role in shaping neuronal excitability. 26745591 0 47 theme channel 36:42 arg1 permeability 44:55 Cav3.2 T-type calcium channel permeability 14:55 Cav3.2 T-type calcium channel permeability 14:55 Modulation of Cav3.2 T-type calcium channel permeability by asparagine-linked glycosylation. 26745591 4 48 theme Asparagine-linked 489:505 arg1 glycosylation 507:519 Asparagine-linked glycosylation 489:519 Asparagine-linked glycosylation 489:519 Asparagine-linked glycosylation has recently emerged as an essential signaling pathway by which the cellular environment can control expression of T-type channels. 26745591 2 49 theme channel 265:271 arg1 expression 273:282 T-type channel expression 258:282 T-type channel expression 258:282 Defects in T-type channel expression have been linked to various neuronal disorders including neuropathic pain and epilepsy. 26745591 0 50 theme calcium 28:34 arg1 permeability 44:55 Cav3.2 T-type calcium channel permeability 14:55 Cav3.2 T-type calcium channel permeability 14:55 Modulation of Cav3.2 T-type calcium channel permeability by asparagine-linked glycosylation. 26745591 4 51 theme cellular 589:596 arg1 environment 598:608 the cellular environment 585:608 the cellular environment 585:608 Asparagine-linked glycosylation has recently emerged as an essential signaling pathway by which the cellular environment can control expression of T-type channels. 26745591 8 52 gly N-glycosylation 1071:1085 arg1 residues 1110:1117 specific asparagine residues 1090:1117 specific asparagine residues 1090:1117 In contrast, N-glycosylation on specific asparagine residues may have an essential role in the conducting function of the channel by enhancing the channel permeability and / or the pore opening of the channel. 26745591 2 53 theme T-type 258:263 arg1 expression 273:282 T-type channel expression 258:282 T-type channel expression 258:282 Defects in T-type channel expression have been linked to various neuronal disorders including neuropathic pain and epilepsy. 26745591 8 54 theme channel 1180:1186 arg1 function 1164:1171 the conducting function 1149:1171 the conducting function of the channel 1149:1186 In contrast, N-glycosylation on specific asparagine residues may have an essential role in the conducting function of the channel by enhancing the channel permeability and / or the pore opening of the channel. 26745591 9 55 theme N-linked 1304:1311 arg1 glycosylation 1313:1325 N-linked glycosylation 1304:1325 N-linked glycosylation of hCav3.2 channels 1304:1345 Our data suggest that modulation of N-linked glycosylation of hCav3.2 channels may play an important physiological role, and could also support the alteration of T-type currents observed in disease states. 26745591 6 56 used used 772:775 arg2 we 769:770 we 769:770 we 769:770 In the present study, we used human Cav3.2 glycosylation-deficient channels to assess the role of N-glycosylation on the gating of the channel. 26745591 0 57 theme permeability 44:55 arg1 Modulation 0:9 Modulation 0:9 Modulation of Cav3.2 T-type calcium channel permeability by asparagine-linked glycosylation. 0:91 Modulation of Cav3.2 T-type calcium channel permeability by asparagine-linked glycosylation. 26745591 9 58 theme T-type 1430:1435 arg1 currents 1437:1444 T-type currents 1430:1444 T-type currents observed in disease states 1430:1471 Our data suggest that modulation of N-linked glycosylation of hCav3.2 channels may play an important physiological role, and could also support the alteration of T-type currents observed in disease states. 26745591 9 59 theme glycosylation 1313:1325 arg1 modulation 1290:1299 modulation 1290:1299 modulation of N-linked glycosylation of hCav3.2 channels 1290:1345 Our data suggest that modulation of N-linked glycosylation of hCav3.2 channels may play an important physiological role, and could also support the alteration of T-type currents observed in disease states. 26745591 6 60 from role 837:840 arg1 gating 868:873 the gating 864:873 the gating of the channel 864:888 In the present study, we used human Cav3.2 glycosylation-deficient channels to assess the role of N-glycosylation on the gating of the channel. 26745591 9 61 theme currents 1437:1444 arg1 alteration 1416:1425 the alteration 1412:1425 the alteration of T-type currents observed in disease states 1412:1471 Our data suggest that modulation of N-linked glycosylation of hCav3.2 channels may play an important physiological role, and could also support the alteration of T-type currents observed in disease states. 26745591 0 62 link asparagine-linked 60:76 arg1 glycosylation 78:90 asparagine-linked glycosylation 60:90 asparagine-linked glycosylation 60:90 Modulation of Cav3.2 T-type calcium channel permeability by asparagine-linked glycosylation. 26745591 9 63 theme hCav3.2 1330:1336 arg1 channels 1338:1345 hCav3.2 channels 1330:1345 hCav3.2 channels 1330:1345 Our data suggest that modulation of N-linked glycosylation of hCav3.2 channels may play an important physiological role, and could also support the alteration of T-type currents observed in disease states. 26745591 6 64 theme glycosylation-deficient 790:812 arg1 channels 814:821 human Cav3.2 glycosylation-deficient channels 777:821 human Cav3.2 glycosylation-deficient channels 777:821 In the present study, we used human Cav3.2 glycosylation-deficient channels to assess the role of N-glycosylation on the gating of the channel. 26745591 1 65 theme nervous 164:170 arg1 system 172:177 the nervous system 160:177 the nervous system where they play an essential role in shaping neuronal excitability 160:244 Low-voltage-gated T-type calcium channels are expressed throughout the nervous system where they play an essential role in shaping neuronal excitability. 26745591 7 66 theme hCav3.2 969:975 arg1 channels 977:984 hCav3.2 channels 969:984 hCav3.2 channels 969:984 Patch-clamp recordings of gating currents revealed that N-glycans attached to hCav3.2 channels have a minimal effect on the functioning of the channel voltage-sensor. 26745591 2 67 attach linked 294:299 arg2 Defects 247:253 Defects 247:253 Defects in T-type channel expression 247:282 Defects in T-type channel expression have been linked to various neuronal disorders including neuropathic pain and epilepsy. 26745591 2 67 attach linked 294:299 arg1 epilepsy 362:369 epilepsy 362:369 epilepsy 362:369 Defects in T-type channel expression have been linked to various neuronal disorders including neuropathic pain and epilepsy. 26745591 2 67 attach linked 294:299 arg1 disorders 321:329 various neuronal disorders 304:329 various neuronal disorders including neuropathic pain and epilepsy 304:369 Defects in T-type channel expression have been linked to various neuronal disorders including neuropathic pain and epilepsy. 26745591 2 67 attach linked 294:299 arg1 pain 353:356 neuropathic pain 341:356 neuropathic pain 341:356 Defects in T-type channel expression have been linked to various neuronal disorders including neuropathic pain and epilepsy. 26745591 8 68 theme channel 1205:1211 arg1 permeability 1213:1224 the channel permeability and / or the pore opening 1201:1250 permeability 1213:1224 In contrast, N-glycosylation on specific asparagine residues may have an essential role in the conducting function of the channel by enhancing the channel permeability and / or the pore opening of the channel. 26745591 6 69 theme channel 882:888 arg1 gating 868:873 the gating 864:873 the gating of the channel 864:888 In the present study, we used human Cav3.2 glycosylation-deficient channels to assess the role of N-glycosylation on the gating of the channel. 26745591 6 70 theme Cav3.2 783:788 arg1 channels 814:821 human Cav3.2 glycosylation-deficient channels 777:821 human Cav3.2 glycosylation-deficient channels 777:821 In the present study, we used human Cav3.2 glycosylation-deficient channels to assess the role of N-glycosylation on the gating of the channel. 26745591 8 71 theme asparagine 1099:1108 arg1 residues 1110:1117 specific asparagine residues 1090:1117 specific asparagine residues 1090:1117 In contrast, N-glycosylation on specific asparagine residues may have an essential role in the conducting function of the channel by enhancing the channel permeability and / or the pore opening of the channel. 26745591 0 72 theme asparagine-linked 60:76 arg1 glycosylation 78:90 asparagine-linked glycosylation 60:90 asparagine-linked glycosylation 60:90 Modulation of Cav3.2 T-type calcium channel permeability by asparagine-linked glycosylation. 26745591 3 73 theme cellular 409:416 arg1 mechanisms 418:427 the cellular mechanisms 405:427 the cellular mechanisms controlling the expression and function of T-type channels 405:486 Currently, little is known about the cellular mechanisms controlling the expression and function of T-type channels. 26745591 6 74 theme human 777:781 arg1 channels 814:821 human Cav3.2 glycosylation-deficient channels 777:821 human Cav3.2 glycosylation-deficient channels 777:821 In the present study, we used human Cav3.2 glycosylation-deficient channels to assess the role of N-glycosylation on the gating of the channel. 26745591 4 75 link Asparagine-linked 489:505 arg1 glycosylation 507:519 Asparagine-linked glycosylation 489:519 Asparagine-linked glycosylation 489:519 Asparagine-linked glycosylation has recently emerged as an essential signaling pathway by which the cellular environment can control expression of T-type channels. 26721430 0 0 theme protein 84:90 arg1 localization 47:58 plasma membrane localization 31:58 plasma membrane localization of multidrug resistance protein 4 (MRP4) 31:99 N-linked glycans do not affect plasma membrane localization of multidrug resistance protein 4 (MRP4) but selectively alter its prostaglandin E2 transport activity. 26721430 2 1 theme apical 453:458 arg1 membrane 482:489 the apical or basolateral plasma membrane 449:489 the apical or basolateral plasma membrane 449:489 MRP4 mediates the ATP-dependent efflux of many endogenous and exogenous solutes across the plasma membrane, and in polarized cells, it localizes to the apical or basolateral plasma membrane depending on the tissue type. 26721430 4 2 theme immunofluorescence 656:673 arg1 studies 675:681 confocal immunofluorescence studies 647:681 confocal immunofluorescence studies 647:681 Furthermore, confocal immunofluorescence studies showed that N-glycans do not affect MRP4's apical membrane localization in polarized LLC-PK1 cells or basolateral membrane localization in polarized MDCKI cells. 26721430 4 3 theme membrane 733:740 arg1 localization 742:753 MRP4's apical membrane localization 719:753 MRP4's apical membrane localization in polarized LLC-PK1 cells or basolateral membrane localization in polarized MDCKI cells 719:842 Furthermore, confocal immunofluorescence studies showed that N-glycans do not affect MRP4's apical membrane localization in polarized LLC-PK1 cells or basolateral membrane localization in polarized MDCKI cells. 26721430 1 4 theme subfamily 217:225 arg1 C 227:227 subfamily C 217:227 subfamily C of the ATP-binding cassette superfamily of membrane transport proteins 217:298 Multidrug resistance protein 4 (MRP4) is a member of subfamily C of the ATP-binding cassette superfamily of membrane transport proteins. 26721430 0 5 theme resistance 73:82 arg1 protein 84:90 multidrug resistance protein 4 63:92 multidrug resistance protein 4 (MRP4) 63:99 N-linked glycans do not affect plasma membrane localization of multidrug resistance protein 4 (MRP4) but selectively alter its prostaglandin E2 transport activity. 26721430 0 5 theme resistance 73:82 arg1 MRP4 95:98 MRP4 95:98 MRP4 95:98 N-linked glycans do not affect plasma membrane localization of multidrug resistance protein 4 (MRP4) but selectively alter its prostaglandin E2 transport activity. 26721430 4 6 from localization 742:753 arg1 cells 776:780 polarized LLC-PK1 cells 758:780 polarized LLC-PK1 cells 758:780 Furthermore, confocal immunofluorescence studies showed that N-glycans do not affect MRP4's apical membrane localization in polarized LLC-PK1 cells or basolateral membrane localization in polarized MDCKI cells. 26721430 4 6 from localization 742:753 arg1 localization 806:817 basolateral membrane localization 785:817 basolateral membrane localization 785:817 Furthermore, confocal immunofluorescence studies showed that N-glycans do not affect MRP4's apical membrane localization in polarized LLC-PK1 cells or basolateral membrane localization in polarized MDCKI cells. 26721430 4 7 theme confocal 647:654 arg1 studies 675:681 confocal immunofluorescence studies 647:681 confocal immunofluorescence studies 647:681 Furthermore, confocal immunofluorescence studies showed that N-glycans do not affect MRP4's apical membrane localization in polarized LLC-PK1 cells or basolateral membrane localization in polarized MDCKI cells. 26721430 1 8 theme C 227:227 arg1 member 207:212 a member 205:212 a member of subfamily C of the ATP-binding cassette superfamily of membrane transport proteins 205:298 Multidrug resistance protein 4 (MRP4) is a member of subfamily C of the ATP-binding cassette superfamily of membrane transport proteins. 26721430 1 8 theme C 227:227 arg1 protein 185:191 Multidrug resistance protein 4 164:193 Multidrug resistance protein 4 (MRP4) 164:200 Multidrug resistance protein 4 (MRP4) is a member of subfamily C of the ATP-binding cassette superfamily of membrane transport proteins. 26721430 5 9 theme estradiol 979:987 arg1 glucuronide 989:999 estradiol glucuronide 979:999 estradiol glucuronide 979:999 However, vesicular transport assays showed that N-glycans differentially affect MRP4's ability to transport prostaglandin E2, but not estradiol glucuronide. 26721430 4 10 theme apical 726:731 arg1 localization 742:753 MRP4's apical membrane localization 719:753 MRP4's apical membrane localization in polarized LLC-PK1 cells or basolateral membrane localization in polarized MDCKI cells 719:842 Furthermore, confocal immunofluorescence studies showed that N-glycans do not affect MRP4's apical membrane localization in polarized LLC-PK1 cells or basolateral membrane localization in polarized MDCKI cells. 26721430 6 11 gly N-glycosylation 1036:1050 arg2 Asn754 1066:1071 Asn754 1066:1071 Asn754 1066:1071 Together these data indicate that N-glycosylation at Asn746 and Asn754 is not essential for plasma membrane localization of MRP4 but cause substrate-selective effects on its transport activity. 26721430 6 11 gly N-glycosylation 1036:1050 arg1 MRP4 1126:1129 MRP4 1126:1129 MRP4 1126:1129 Together these data indicate that N-glycosylation at Asn746 and Asn754 is not essential for plasma membrane localization of MRP4 but cause substrate-selective effects on its transport activity. 26721430 6 11 gly N-glycosylation 1036:1050 arg1 Asn746 1055:1060 Asn746 1055:1060 Asn746 1055:1060 Together these data indicate that N-glycosylation at Asn746 and Asn754 is not essential for plasma membrane localization of MRP4 but cause substrate-selective effects on its transport activity. 26721430 6 11 gly N-glycosylation 1036:1050 arg1 plasma 1094:1099 plasma membrane localization 1094:1121 plasma membrane localization of MRP4 1094:1129 Together these data indicate that N-glycosylation at Asn746 and Asn754 is not essential for plasma membrane localization of MRP4 but cause substrate-selective effects on its transport activity. 26721430 6 11 gly N-glycosylation 1036:1050 arg1 membrane 1101:1108 plasma membrane localization 1094:1121 plasma membrane localization of MRP4 1094:1129 Together these data indicate that N-glycosylation at Asn746 and Asn754 is not essential for plasma membrane localization of MRP4 but cause substrate-selective effects on its transport activity. 26721430 6 11 gly N-glycosylation 1036:1050 arg1 Asn754 1066:1071 Asn754 1066:1071 Asn754 1066:1071 Together these data indicate that N-glycosylation at Asn746 and Asn754 is not essential for plasma membrane localization of MRP4 but cause substrate-selective effects on its transport activity. 26721430 6 11 gly N-glycosylation 1036:1050 arg2 Asn746 1055:1060 Asn746 1055:1060 Asn746 1055:1060 Together these data indicate that N-glycosylation at Asn746 and Asn754 is not essential for plasma membrane localization of MRP4 but cause substrate-selective effects on its transport activity. 26721430 4 12 theme polarized 822:830 arg1 cells 838:842 polarized MDCKI cells 822:842 polarized MDCKI cells 822:842 Furthermore, confocal immunofluorescence studies showed that N-glycans do not affect MRP4's apical membrane localization in polarized LLC-PK1 cells or basolateral membrane localization in polarized MDCKI cells. 26721430 0 13 link N-linked 0:7 arg1 glycans 9:15 N-linked glycans 0:15 N-linked glycans 0:15 N-linked glycans do not affect plasma membrane localization of multidrug resistance protein 4 (MRP4) but selectively alter its prostaglandin E2 transport activity. 26721430 6 14 theme transport 1176:1184 arg1 activity 1186:1193 its transport activity 1172:1193 its transport activity 1172:1193 Together these data indicate that N-glycosylation at Asn746 and Asn754 is not essential for plasma membrane localization of MRP4 but cause substrate-selective effects on its transport activity. 26721430 2 15 theme exogenous 363:371 arg1 solutes 373:379 many endogenous and exogenous solutes 343:379 many endogenous and exogenous solutes 343:379 MRP4 mediates the ATP-dependent efflux of many endogenous and exogenous solutes across the plasma membrane, and in polarized cells, it localizes to the apical or basolateral plasma membrane depending on the tissue type. 26721430 2 16 theme plasma 475:480 arg1 membrane 482:489 the apical or basolateral plasma membrane 449:489 the apical or basolateral plasma membrane 449:489 MRP4 mediates the ATP-dependent efflux of many endogenous and exogenous solutes across the plasma membrane, and in polarized cells, it localizes to the apical or basolateral plasma membrane depending on the tissue type. 26721430 2 17 theme polarized 416:424 arg1 cells 426:430 polarized cells 416:430 polarized cells 416:430 MRP4 mediates the ATP-dependent efflux of many endogenous and exogenous solutes across the plasma membrane, and in polarized cells, it localizes to the apical or basolateral plasma membrane depending on the tissue type. 26721430 1 18 theme Multidrug 164:172 arg1 member 207:212 a member 205:212 a member of subfamily C of the ATP-binding cassette superfamily of membrane transport proteins 205:298 Multidrug resistance protein 4 (MRP4) is a member of subfamily C of the ATP-binding cassette superfamily of membrane transport proteins. 26721430 1 18 theme Multidrug 164:172 arg1 protein 185:191 Multidrug resistance protein 4 164:193 Multidrug resistance protein 4 (MRP4) 164:200 Multidrug resistance protein 4 (MRP4) is a member of subfamily C of the ATP-binding cassette superfamily of membrane transport proteins. 26721430 1 18 theme Multidrug 164:172 arg1 MRP4 196:199 MRP4 196:199 MRP4 196:199 Multidrug resistance protein 4 (MRP4) is a member of subfamily C of the ATP-binding cassette superfamily of membrane transport proteins. 26721430 2 19 theme basolateral 463:473 arg1 membrane 482:489 the apical or basolateral plasma membrane 449:489 the apical or basolateral plasma membrane 449:489 MRP4 mediates the ATP-dependent efflux of many endogenous and exogenous solutes across the plasma membrane, and in polarized cells, it localizes to the apical or basolateral plasma membrane depending on the tissue type. 26721430 3 20 from Asn754 626:631 arg1 N-glycosylated 597:610 N-glycosylated 597:610 N-glycosylated 597:610 MRP4 is a 170 kDa glycoprotein and here we show that MRP4 is simultaneously N-glycosylated at Asn746 and Asn754. 26721430 1 21 theme resistance 174:183 arg1 member 207:212 a member 205:212 a member of subfamily C of the ATP-binding cassette superfamily of membrane transport proteins 205:298 Multidrug resistance protein 4 (MRP4) is a member of subfamily C of the ATP-binding cassette superfamily of membrane transport proteins. 26721430 1 21 theme resistance 174:183 arg1 protein 185:191 Multidrug resistance protein 4 164:193 Multidrug resistance protein 4 (MRP4) 164:200 Multidrug resistance protein 4 (MRP4) is a member of subfamily C of the ATP-binding cassette superfamily of membrane transport proteins. 26721430 1 21 theme resistance 174:183 arg1 MRP4 196:199 MRP4 196:199 MRP4 196:199 Multidrug resistance protein 4 (MRP4) is a member of subfamily C of the ATP-binding cassette superfamily of membrane transport proteins. 26721430 0 22 theme N-linked 0:7 arg1 glycans 9:15 N-linked glycans 0:15 N-linked glycans 0:15 N-linked glycans do not affect plasma membrane localization of multidrug resistance protein 4 (MRP4) but selectively alter its prostaglandin E2 transport activity. 26721430 1 23 theme ATP-binding 236:246 arg1 superfamily 257:267 the ATP-binding cassette superfamily 232:267 the ATP-binding cassette superfamily of membrane transport proteins 232:298 Multidrug resistance protein 4 (MRP4) is a member of subfamily C of the ATP-binding cassette superfamily of membrane transport proteins. 26721430 4 24 theme MDCKI 832:836 arg1 cells 838:842 polarized MDCKI cells 822:842 polarized MDCKI cells 822:842 Furthermore, confocal immunofluorescence studies showed that N-glycans do not affect MRP4's apical membrane localization in polarized LLC-PK1 cells or basolateral membrane localization in polarized MDCKI cells. 26721430 6 25 from Asn746 1055:1060 arg1 N-glycosylation 1036:1050 N-glycosylation 1036:1050 N-glycosylation at Asn746 and Asn754 1036:1071 Together these data indicate that N-glycosylation at Asn746 and Asn754 is not essential for plasma membrane localization of MRP4 but cause substrate-selective effects on its transport activity. 26721430 3 26 theme 170 531:533 arg1 kDa 535:537 kDa 535:537 kDa 535:537 MRP4 is a 170 kDa glycoprotein and here we show that MRP4 is simultaneously N-glycosylated at Asn746 and Asn754. 26721430 5 27 theme vesicular 854:862 arg1 transport 864:872 vesicular transport 854:872 vesicular transport assays 854:879 However, vesicular transport assays showed that N-glycans differentially affect MRP4's ability to transport prostaglandin E2, but not estradiol glucuronide. 26721430 1 28 theme cassette 248:255 arg1 superfamily 257:267 the ATP-binding cassette superfamily 232:267 the ATP-binding cassette superfamily of membrane transport proteins 232:298 Multidrug resistance protein 4 (MRP4) is a member of subfamily C of the ATP-binding cassette superfamily of membrane transport proteins. 26721430 6 29 theme substrate-selective 1141:1159 arg1 effects 1161:1167 substrate-selective effects 1141:1167 substrate-selective effects on its transport activity 1141:1193 Together these data indicate that N-glycosylation at Asn746 and Asn754 is not essential for plasma membrane localization of MRP4 but cause substrate-selective effects on its transport activity. 26721430 6 30 from Asn754 1066:1071 arg1 N-glycosylation 1036:1050 N-glycosylation 1036:1050 N-glycosylation at Asn746 and Asn754 1036:1071 Together these data indicate that N-glycosylation at Asn746 and Asn754 is not essential for plasma membrane localization of MRP4 but cause substrate-selective effects on its transport activity. 26721430 1 31 theme superfamily 257:267 arg1 C 227:227 subfamily C 217:227 subfamily C of the ATP-binding cassette superfamily of membrane transport proteins 217:298 Multidrug resistance protein 4 (MRP4) is a member of subfamily C of the ATP-binding cassette superfamily of membrane transport proteins. 26721430 5 32 theme transport 864:872 arg1 assays 874:879 vesicular transport assays 854:879 vesicular transport assays 854:879 However, vesicular transport assays showed that N-glycans differentially affect MRP4's ability to transport prostaglandin E2, but not estradiol glucuronide. 26721430 0 33 theme plasma 31:36 arg1 localization 47:58 plasma membrane localization 31:58 plasma membrane localization of multidrug resistance protein 4 (MRP4) 31:99 N-linked glycans do not affect plasma membrane localization of multidrug resistance protein 4 (MRP4) but selectively alter its prostaglandin E2 transport activity. 26721430 2 34 theme tissue 508:513 arg1 type 515:518 the tissue type 504:518 the tissue type 504:518 MRP4 mediates the ATP-dependent efflux of many endogenous and exogenous solutes across the plasma membrane, and in polarized cells, it localizes to the apical or basolateral plasma membrane depending on the tissue type. 26721430 3 35 gly glycoprotein 539:550 arg1 glycoprotein 539:550 a 170 kDa glycoprotein 529:550 a 170 kDa glycoprotein 529:550 MRP4 is a 170 kDa glycoprotein and here we show that MRP4 is simultaneously N-glycosylated at Asn746 and Asn754. 26721430 3 35 gly glycoprotein 539:550 arg1 MRP4 521:524 MRP4 521:524 MRP4 521:524 MRP4 is a 170 kDa glycoprotein and here we show that MRP4 is simultaneously N-glycosylated at Asn746 and Asn754. 26721430 4 36 theme basolateral 785:795 arg1 localization 806:817 basolateral membrane localization 785:817 basolateral membrane localization 785:817 Furthermore, confocal immunofluorescence studies showed that N-glycans do not affect MRP4's apical membrane localization in polarized LLC-PK1 cells or basolateral membrane localization in polarized MDCKI cells. 26721430 6 37 from effects 1161:1167 arg1 activity 1186:1193 its transport activity 1172:1193 its transport activity 1172:1193 Together these data indicate that N-glycosylation at Asn746 and Asn754 is not essential for plasma membrane localization of MRP4 but cause substrate-selective effects on its transport activity. 26721430 2 38 theme plasma 392:397 arg1 membrane 399:406 the plasma membrane 388:406 the plasma membrane 388:406 MRP4 mediates the ATP-dependent efflux of many endogenous and exogenous solutes across the plasma membrane, and in polarized cells, it localizes to the apical or basolateral plasma membrane depending on the tissue type. 26721430 1 39 theme membrane 272:279 arg1 proteins 291:298 membrane transport proteins 272:298 membrane transport proteins 272:298 Multidrug resistance protein 4 (MRP4) is a member of subfamily C of the ATP-binding cassette superfamily of membrane transport proteins. 26721430 3 40 gly N-glycosylated 597:610 arg2 Asn754 626:631 Asn754 626:631 Asn754 626:631 MRP4 is a 170 kDa glycoprotein and here we show that MRP4 is simultaneously N-glycosylated at Asn746 and Asn754. 26721430 3 40 gly N-glycosylated 597:610 arg2 Asn746 615:620 Asn746 615:620 Asn746 615:620 MRP4 is a 170 kDa glycoprotein and here we show that MRP4 is simultaneously N-glycosylated at Asn746 and Asn754. 26721430 3 40 gly N-glycosylated 597:610 arg1 MRP4 574:577 MRP4 574:577 MRP4 574:577 MRP4 is a 170 kDa glycoprotein and here we show that MRP4 is simultaneously N-glycosylated at Asn746 and Asn754. 26721430 4 41 from localization 806:817 arg1 cells 838:842 polarized MDCKI cells 822:842 polarized MDCKI cells 822:842 Furthermore, confocal immunofluorescence studies showed that N-glycans do not affect MRP4's apical membrane localization in polarized LLC-PK1 cells or basolateral membrane localization in polarized MDCKI cells. 26721430 1 42 theme transport 281:289 arg1 proteins 291:298 membrane transport proteins 272:298 membrane transport proteins 272:298 Multidrug resistance protein 4 (MRP4) is a member of subfamily C of the ATP-binding cassette superfamily of membrane transport proteins. 26721430 0 43 theme E2 141:142 arg1 activity 154:161 its prostaglandin E2 transport activity 123:161 its prostaglandin E2 transport activity 123:161 N-linked glycans do not affect plasma membrane localization of multidrug resistance protein 4 (MRP4) but selectively alter its prostaglandin E2 transport activity. 26721430 3 44 theme kDa 535:537 arg1 glycoprotein 539:550 a 170 kDa glycoprotein 529:550 a 170 kDa glycoprotein 529:550 MRP4 is a 170 kDa glycoprotein and here we show that MRP4 is simultaneously N-glycosylated at Asn746 and Asn754. 26721430 3 44 theme kDa 535:537 arg1 MRP4 521:524 MRP4 521:524 MRP4 521:524 MRP4 is a 170 kDa glycoprotein and here we show that MRP4 is simultaneously N-glycosylated at Asn746 and Asn754. 26721430 6 45 theme membrane 1101:1108 arg1 localization 1110:1121 plasma membrane localization 1094:1121 plasma membrane localization of MRP4 1094:1129 Together these data indicate that N-glycosylation at Asn746 and Asn754 is not essential for plasma membrane localization of MRP4 but cause substrate-selective effects on its transport activity. 26721430 2 46 theme ATP-dependent 319:331 arg1 efflux 333:338 the ATP-dependent efflux 315:338 the ATP-dependent efflux of many endogenous and exogenous solutes across the plasma membrane 315:406 MRP4 mediates the ATP-dependent efflux of many endogenous and exogenous solutes across the plasma membrane, and in polarized cells, it localizes to the apical or basolateral plasma membrane depending on the tissue type. 26721430 0 47 theme membrane 38:45 arg1 localization 47:58 plasma membrane localization 31:58 plasma membrane localization of multidrug resistance protein 4 (MRP4) 31:99 N-linked glycans do not affect plasma membrane localization of multidrug resistance protein 4 (MRP4) but selectively alter its prostaglandin E2 transport activity. 26721430 1 48 theme proteins 291:298 arg1 superfamily 257:267 the ATP-binding cassette superfamily 232:267 the ATP-binding cassette superfamily of membrane transport proteins 232:298 Multidrug resistance protein 4 (MRP4) is a member of subfamily C of the ATP-binding cassette superfamily of membrane transport proteins. 26721430 0 49 theme prostaglandin 127:139 arg1 activity 154:161 its prostaglandin E2 transport activity 123:161 its prostaglandin E2 transport activity 123:161 N-linked glycans do not affect plasma membrane localization of multidrug resistance protein 4 (MRP4) but selectively alter its prostaglandin E2 transport activity. 26721430 4 50 theme membrane 797:804 arg1 localization 806:817 basolateral membrane localization 785:817 basolateral membrane localization 785:817 Furthermore, confocal immunofluorescence studies showed that N-glycans do not affect MRP4's apical membrane localization in polarized LLC-PK1 cells or basolateral membrane localization in polarized MDCKI cells. 26721430 6 51 theme MRP4 1126:1129 arg1 localization 1110:1121 plasma membrane localization 1094:1121 plasma membrane localization of MRP4 1094:1129 Together these data indicate that N-glycosylation at Asn746 and Asn754 is not essential for plasma membrane localization of MRP4 but cause substrate-selective effects on its transport activity. 26721430 4 52 theme polarized 758:766 arg1 cells 776:780 polarized LLC-PK1 cells 758:780 polarized LLC-PK1 cells 758:780 Furthermore, confocal immunofluorescence studies showed that N-glycans do not affect MRP4's apical membrane localization in polarized LLC-PK1 cells or basolateral membrane localization in polarized MDCKI cells. 26721430 0 53 theme transport 144:152 arg1 activity 154:161 its prostaglandin E2 transport activity 123:161 its prostaglandin E2 transport activity 123:161 N-linked glycans do not affect plasma membrane localization of multidrug resistance protein 4 (MRP4) but selectively alter its prostaglandin E2 transport activity. 26721430 5 54 theme prostaglandin 953:965 arg1 E2 967:968 prostaglandin E2 953:968 prostaglandin E2 953:968 However, vesicular transport assays showed that N-glycans differentially affect MRP4's ability to transport prostaglandin E2, but not estradiol glucuronide. 26721430 4 55 from cells 776:780 arg1 cells 838:842 polarized MDCKI cells 822:842 polarized MDCKI cells 822:842 Furthermore, confocal immunofluorescence studies showed that N-glycans do not affect MRP4's apical membrane localization in polarized LLC-PK1 cells or basolateral membrane localization in polarized MDCKI cells. 26721430 6 56 theme plasma 1094:1099 arg1 localization 1110:1121 plasma membrane localization 1094:1121 plasma membrane localization of MRP4 1094:1129 Together these data indicate that N-glycosylation at Asn746 and Asn754 is not essential for plasma membrane localization of MRP4 but cause substrate-selective effects on its transport activity. 26721430 0 57 theme multidrug 63:71 arg1 protein 84:90 multidrug resistance protein 4 63:92 multidrug resistance protein 4 (MRP4) 63:99 N-linked glycans do not affect plasma membrane localization of multidrug resistance protein 4 (MRP4) but selectively alter its prostaglandin E2 transport activity. 26721430 0 57 theme multidrug 63:71 arg1 MRP4 95:98 MRP4 95:98 MRP4 95:98 N-linked glycans do not affect plasma membrane localization of multidrug resistance protein 4 (MRP4) but selectively alter its prostaglandin E2 transport activity. 26721430 2 58 theme endogenous 348:357 arg1 solutes 373:379 many endogenous and exogenous solutes 343:379 many endogenous and exogenous solutes 343:379 MRP4 mediates the ATP-dependent efflux of many endogenous and exogenous solutes across the plasma membrane, and in polarized cells, it localizes to the apical or basolateral plasma membrane depending on the tissue type. 26721430 2 59 theme solutes 373:379 arg1 efflux 333:338 the ATP-dependent efflux 315:338 the ATP-dependent efflux of many endogenous and exogenous solutes across the plasma membrane 315:406 MRP4 mediates the ATP-dependent efflux of many endogenous and exogenous solutes across the plasma membrane, and in polarized cells, it localizes to the apical or basolateral plasma membrane depending on the tissue type. 26721430 3 60 from Asn746 615:620 arg1 N-glycosylated 597:610 N-glycosylated 597:610 N-glycosylated 597:610 MRP4 is a 170 kDa glycoprotein and here we show that MRP4 is simultaneously N-glycosylated at Asn746 and Asn754. 26721430 4 61 theme LLC-PK1 768:774 arg1 cells 776:780 polarized LLC-PK1 cells 758:780 polarized LLC-PK1 cells 758:780 Furthermore, confocal immunofluorescence studies showed that N-glycans do not affect MRP4's apical membrane localization in polarized LLC-PK1 cells or basolateral membrane localization in polarized MDCKI cells. 26721430 2 62 theme many 343:346 arg1 solutes 373:379 many endogenous and exogenous solutes 343:379 many endogenous and exogenous solutes 343:379 MRP4 mediates the ATP-dependent efflux of many endogenous and exogenous solutes across the plasma membrane, and in polarized cells, it localizes to the apical or basolateral plasma membrane depending on the tissue type. 25340554 2 0 gly glycoprotein 316:327 arg1 receptor 351:358 a common receptor 342:358 a common receptor 342:358 IL-6 cytokines bind to their specific receptors and activate glycoprotein 130 (gp130), a common receptor, followed by further activation of STAT3 and extracellular signal-regulated kinase (ERK)1/2 through janus kinases (JAKs); however the importance of glycosylation of gp130 remains to be elucidated in cardiac myocytes. 25340554 2 0 gly glycoprotein 316:327 arg1 glycoprotein 316:327 glycoprotein 130 316:331 glycoprotein 130 (gp130) 316:339 IL-6 cytokines bind to their specific receptors and activate glycoprotein 130 (gp130), a common receptor, followed by further activation of STAT3 and extracellular signal-regulated kinase (ERK)1/2 through janus kinases (JAKs); however the importance of glycosylation of gp130 remains to be elucidated in cardiac myocytes. 25340554 2 0 gly glycoprotein 316:327 arg1 gp130 334:338 gp130 334:338 gp130 334:338 IL-6 cytokines bind to their specific receptors and activate glycoprotein 130 (gp130), a common receptor, followed by further activation of STAT3 and extracellular signal-regulated kinase (ERK)1/2 through janus kinases (JAKs); however the importance of glycosylation of gp130 remains to be elucidated in cardiac myocytes. 25340554 5 1 theme Tm 859:860 arg1 treatment 862:870 Tm treatment 859:870 Tm treatment 859:870 Tm treatment inhibited leukemia inhibitory factor (LIF)-mediated activation of STAT3 and ERK1/2. 25340554 4 2 theme unglycosylated 839:852 arg1 one 854:856 its unglycosylated one 835:856 its unglycosylated one 835:856 In cardiomyocytes, the treatment with Tm completely replaced the glycosylated form of gp130 with its unglycosylated one. 25340554 7 3 theme protein-tyrosine 1176:1191 arg1 phosphatase 1193:1203 protein-tyrosine phosphatase 1176:1203 protein-tyrosine phosphatase 1B (PTP1B) 1176:1214 Interestingly, Tm inhibited the activation of JAKs 1 and 2, without influencing the expression of suppressor of cytokine signalings (SOCSs) and protein-tyrosine phosphatase 1B (PTP1B), which are endogenous inhibitors of JAKs. 25340554 9 4 theme gp130 1667:1671 arg1 glycosylation 1650:1662 glycosylation 1650:1662 glycosylation of gp130 1650:1671 Collectively, these findings indicate that glycosylation of gp130 is essential for signal transduction of IL-6 family cytokines in cardiomyocytes. 25340554 8 5 gly glycosylation 1340:1352 arg1 receptors 1372:1380 their specific receptors 1357:1380 their specific receptors 1357:1380 To exclude the possibility that Tm blocks LIF and IL-11 signals by inhibiting the glycosylation of their specific receptors, we investigated whether the stimulation with IL-6 plus soluble IL-6 receptor (sIL-6R) could transduce their signals in Tm-treated cardiomyocytes and found that this stimulation was unable to activate the downstream signals. 25340554 9 6 theme IL-6 1713:1716 arg1 cytokines 1725:1733 IL-6 family cytokines 1713:1733 IL-6 family cytokines 1713:1733 Collectively, these findings indicate that glycosylation of gp130 is essential for signal transduction of IL-6 family cytokines in cardiomyocytes. 25340554 8 7 theme IL-6 1446:1449 arg1 sIL-6R 1461:1466 sIL-6R 1461:1466 sIL-6R 1461:1466 To exclude the possibility that Tm blocks LIF and IL-11 signals by inhibiting the glycosylation of their specific receptors, we investigated whether the stimulation with IL-6 plus soluble IL-6 receptor (sIL-6R) could transduce their signals in Tm-treated cardiomyocytes and found that this stimulation was unable to activate the downstream signals. 25340554 8 7 theme IL-6 1446:1449 arg1 receptor 1451:1458 soluble IL-6 receptor 1438:1458 soluble IL-6 receptor (sIL-6R) 1438:1467 To exclude the possibility that Tm blocks LIF and IL-11 signals by inhibiting the glycosylation of their specific receptors, we investigated whether the stimulation with IL-6 plus soluble IL-6 receptor (sIL-6R) could transduce their signals in Tm-treated cardiomyocytes and found that this stimulation was unable to activate the downstream signals. 25340554 5 8 theme leukemia 882:889 arg1 factor 902:907 leukemia inhibitory factor 882:907 leukemia inhibitory factor 882:907 Tm treatment inhibited leukemia inhibitory factor (LIF)-mediated activation of STAT3 and ERK1/2. 25340554 7 9 theme JAKs 1078:1081 arg1 activation 1064:1073 the activation 1060:1073 the activation of JAKs 1 and 2 1060:1089 Interestingly, Tm inhibited the activation of JAKs 1 and 2, without influencing the expression of suppressor of cytokine signalings (SOCSs) and protein-tyrosine phosphatase 1B (PTP1B), which are endogenous inhibitors of JAKs. 25340554 0 10 theme family 98:103 arg1 cytokines 105:113 IL-6 family cytokines 93:113 IL-6 family cytokines 93:113 The inhibition of N-glycosylation of glycoprotein 130 molecule abolishes STAT3 activation by IL-6 family cytokines in cultured cardiac myocytes. 25340554 8 11 theme soluble 1438:1444 arg1 sIL-6R 1461:1466 sIL-6R 1461:1466 sIL-6R 1461:1466 To exclude the possibility that Tm blocks LIF and IL-11 signals by inhibiting the glycosylation of their specific receptors, we investigated whether the stimulation with IL-6 plus soluble IL-6 receptor (sIL-6R) could transduce their signals in Tm-treated cardiomyocytes and found that this stimulation was unable to activate the downstream signals. 25340554 8 11 theme soluble 1438:1444 arg1 receptor 1451:1458 soluble IL-6 receptor 1438:1458 soluble IL-6 receptor (sIL-6R) 1438:1467 To exclude the possibility that Tm blocks LIF and IL-11 signals by inhibiting the glycosylation of their specific receptors, we investigated whether the stimulation with IL-6 plus soluble IL-6 receptor (sIL-6R) could transduce their signals in Tm-treated cardiomyocytes and found that this stimulation was unable to activate the downstream signals. 25340554 5 12 theme STAT3 938:942 arg1 activation 924:933 leukemia inhibitory factor (LIF)-mediated activation 882:933 leukemia inhibitory factor (LIF)-mediated activation of STAT3 and ERK1/2 882:953 Tm treatment inhibited leukemia inhibitory factor (LIF)-mediated activation of STAT3 and ERK1/2. 25340554 4 13 with treatment 761:769 arg1 Tm 776:777 Tm 776:777 Tm 776:777 In cardiomyocytes, the treatment with Tm completely replaced the glycosylated form of gp130 with its unglycosylated one. 25340554 0 14 theme IL-6 93:96 arg1 cytokines 105:113 IL-6 family cytokines 93:113 IL-6 family cytokines 93:113 The inhibition of N-glycosylation of glycoprotein 130 molecule abolishes STAT3 activation by IL-6 family cytokines in cultured cardiac myocytes. 25340554 9 15 theme cytokines 1725:1733 arg1 transduction 1697:1708 signal transduction 1690:1708 signal transduction of IL-6 family cytokines in cardiomyocytes 1690:1751 Collectively, these findings indicate that glycosylation of gp130 is essential for signal transduction of IL-6 family cytokines in cardiomyocytes. 25340554 7 16 theme phosphatase 1193:1203 arg1 1B 1205:1206 protein-tyrosine phosphatase 1B 1176:1206 protein-tyrosine phosphatase 1B (PTP1B) 1176:1214 Interestingly, Tm inhibited the activation of JAKs 1 and 2, without influencing the expression of suppressor of cytokine signalings (SOCSs) and protein-tyrosine phosphatase 1B (PTP1B), which are endogenous inhibitors of JAKs. 25340554 7 16 theme phosphatase 1193:1203 arg1 PTP1B 1209:1213 PTP1B 1209:1213 PTP1B 1209:1213 Interestingly, Tm inhibited the activation of JAKs 1 and 2, without influencing the expression of suppressor of cytokine signalings (SOCSs) and protein-tyrosine phosphatase 1B (PTP1B), which are endogenous inhibitors of JAKs. 25340554 2 17 gly glycosylation 508:520 arg1 gp130 525:529 gp130 525:529 gp130 525:529 IL-6 cytokines bind to their specific receptors and activate glycoprotein 130 (gp130), a common receptor, followed by further activation of STAT3 and extracellular signal-regulated kinase (ERK)1/2 through janus kinases (JAKs); however the importance of glycosylation of gp130 remains to be elucidated in cardiac myocytes. 25340554 8 18 dep LIF 1300:1302 arg1 signals 1314:1320 signals 1314:1320 signals 1314:1320 To exclude the possibility that Tm blocks LIF and IL-11 signals by inhibiting the glycosylation of their specific receptors, we investigated whether the stimulation with IL-6 plus soluble IL-6 receptor (sIL-6R) could transduce their signals in Tm-treated cardiomyocytes and found that this stimulation was unable to activate the downstream signals. 25340554 7 19 theme suppressor 1130:1139 arg1 inhibitors 1238:1247 endogenous inhibitors 1227:1247 endogenous inhibitors of JAKs 1227:1255 Interestingly, Tm inhibited the activation of JAKs 1 and 2, without influencing the expression of suppressor of cytokine signalings (SOCSs) and protein-tyrosine phosphatase 1B (PTP1B), which are endogenous inhibitors of JAKs. 25340554 7 19 theme suppressor 1130:1139 arg1 expression 1116:1125 the expression 1112:1125 the expression 1112:1125 Interestingly, Tm inhibited the activation of JAKs 1 and 2, without influencing the expression of suppressor of cytokine signalings (SOCSs) and protein-tyrosine phosphatase 1B (PTP1B), which are endogenous inhibitors of JAKs. 25340554 3 20 theme enzyme 695:700 arg1 inhibitor 682:690 an inhibitor 679:690 an inhibitor of enzyme involved in N-linked glycosylation 679:735 In this study, we examined the biological significance of gp130 glycosylation using tunicamycin (Tm), an inhibitor of enzyme involved in N-linked glycosylation. 25340554 3 20 theme enzyme 695:700 arg1 tunicamycin 661:671 gp130 glycosylation using tunicamycin 635:671 gp130 glycosylation using tunicamycin (Tm) 635:676 In this study, we examined the biological significance of gp130 glycosylation using tunicamycin (Tm), an inhibitor of enzyme involved in N-linked glycosylation. 25340554 9 21 theme family 1718:1723 arg1 cytokines 1725:1733 IL-6 family cytokines 1713:1733 IL-6 family cytokines 1713:1733 Collectively, these findings indicate that glycosylation of gp130 is essential for signal transduction of IL-6 family cytokines in cardiomyocytes. 25340554 9 22 from transduction 1697:1708 arg1 cardiomyocytes 1738:1751 cardiomyocytes 1738:1751 cardiomyocytes 1738:1751 Collectively, these findings indicate that glycosylation of gp130 is essential for signal transduction of IL-6 family cytokines in cardiomyocytes. 25340554 5 23 theme ERK1/2 948:953 arg1 activation 924:933 leukemia inhibitory factor (LIF)-mediated activation 882:933 leukemia inhibitory factor (LIF)-mediated activation of STAT3 and ERK1/2 882:953 Tm treatment inhibited leukemia inhibitory factor (LIF)-mediated activation of STAT3 and ERK1/2. 25340554 7 24 theme JAKs 1252:1255 arg1 inhibitors 1238:1247 endogenous inhibitors 1227:1247 endogenous inhibitors of JAKs 1227:1255 Interestingly, Tm inhibited the activation of JAKs 1 and 2, without influencing the expression of suppressor of cytokine signalings (SOCSs) and protein-tyrosine phosphatase 1B (PTP1B), which are endogenous inhibitors of JAKs. 25340554 7 24 theme JAKs 1252:1255 arg1 expression 1116:1125 the expression 1112:1125 the expression 1112:1125 Interestingly, Tm inhibited the activation of JAKs 1 and 2, without influencing the expression of suppressor of cytokine signalings (SOCSs) and protein-tyrosine phosphatase 1B (PTP1B), which are endogenous inhibitors of JAKs. 25340554 1 25 theme family 166:171 arg1 cytokines 173:181 Interleukin-6 (IL-6) family cytokines 145:181 Interleukin-6 (IL-6) family cytokines 145:181 Interleukin-6 (IL-6) family cytokines play important roles in cardioprotection against pathological stresses. 25340554 7 26 theme cytokine 1144:1151 arg1 SOCSs 1165:1169 SOCSs 1165:1169 SOCSs 1165:1169 Interestingly, Tm inhibited the activation of JAKs 1 and 2, without influencing the expression of suppressor of cytokine signalings (SOCSs) and protein-tyrosine phosphatase 1B (PTP1B), which are endogenous inhibitors of JAKs. 25340554 7 26 theme cytokine 1144:1151 arg1 signalings 1153:1162 cytokine signalings 1144:1162 cytokine signalings (SOCSs) 1144:1170 Interestingly, Tm inhibited the activation of JAKs 1 and 2, without influencing the expression of suppressor of cytokine signalings (SOCSs) and protein-tyrosine phosphatase 1B (PTP1B), which are endogenous inhibitors of JAKs. 25340554 2 27 theme specific 284:291 arg1 receptors 293:301 their specific receptors 278:301 their specific receptors 278:301 IL-6 cytokines bind to their specific receptors and activate glycoprotein 130 (gp130), a common receptor, followed by further activation of STAT3 and extracellular signal-regulated kinase (ERK)1/2 through janus kinases (JAKs); however the importance of glycosylation of gp130 remains to be elucidated in cardiac myocytes. 25340554 4 28 gly unglycosylated 839:852 arg1 one 854:856 its unglycosylated one 835:856 its unglycosylated one 835:856 In cardiomyocytes, the treatment with Tm completely replaced the glycosylated form of gp130 with its unglycosylated one. 25340554 7 29 theme 1B 1205:1206 arg1 suppressor 1130:1139 suppressor 1130:1139 suppressor of cytokine signalings (SOCSs) and protein-tyrosine phosphatase 1B (PTP1B) 1130:1214 Interestingly, Tm inhibited the activation of JAKs 1 and 2, without influencing the expression of suppressor of cytokine signalings (SOCSs) and protein-tyrosine phosphatase 1B (PTP1B), which are endogenous inhibitors of JAKs. 25340554 9 30 gly glycosylation 1650:1662 arg1 cytokines 1725:1733 IL-6 family cytokines 1713:1733 IL-6 family cytokines 1713:1733 Collectively, these findings indicate that glycosylation of gp130 is essential for signal transduction of IL-6 family cytokines in cardiomyocytes. 25340554 9 30 gly glycosylation 1650:1662 arg1 signal 1690:1695 signal transduction 1690:1708 signal transduction of IL-6 family cytokines in cardiomyocytes 1690:1751 Collectively, these findings indicate that glycosylation of gp130 is essential for signal transduction of IL-6 family cytokines in cardiomyocytes. 25340554 9 30 gly glycosylation 1650:1662 arg1 gp130 1667:1671 gp130 1667:1671 gp130 1667:1671 Collectively, these findings indicate that glycosylation of gp130 is essential for signal transduction of IL-6 family cytokines in cardiomyocytes. 25340554 6 31 theme Tm 1028:1029 arg1 presence 1016:1023 the presence 1012:1023 the presence of Tm 1012:1029 Similarly, IL-11 failed to activate STAT3 and ERK1/2 in the presence of Tm. 25340554 3 32 theme N-linked 714:721 arg1 glycosylation 723:735 N-linked glycosylation 714:735 N-linked glycosylation 714:735 In this study, we examined the biological significance of gp130 glycosylation using tunicamycin (Tm), an inhibitor of enzyme involved in N-linked glycosylation. 25340554 4 33 theme gp130 824:828 arg1 form 816:819 the glycosylated form 799:819 the glycosylated form of gp130 799:828 In cardiomyocytes, the treatment with Tm completely replaced the glycosylated form of gp130 with its unglycosylated one. 25340554 5 34 theme -mediated 914:922 arg1 activation 924:933 leukemia inhibitory factor (LIF)-mediated activation 882:933 leukemia inhibitory factor (LIF)-mediated activation of STAT3 and ERK1/2 882:953 Tm treatment inhibited leukemia inhibitory factor (LIF)-mediated activation of STAT3 and ERK1/2. 25340554 1 35 theme important 188:196 arg1 roles 198:202 important roles 188:202 important roles 188:202 Interleukin-6 (IL-6) family cytokines play important roles in cardioprotection against pathological stresses. 25340554 2 36 theme ERK 444:446 arg1 activation 381:390 further activation 373:390 further activation of STAT3 and extracellular signal-regulated kinase (ERK)1/2 through janus kinases (JAKs) 373:479 IL-6 cytokines bind to their specific receptors and activate glycoprotein 130 (gp130), a common receptor, followed by further activation of STAT3 and extracellular signal-regulated kinase (ERK)1/2 through janus kinases (JAKs); however the importance of glycosylation of gp130 remains to be elucidated in cardiac myocytes. 25340554 0 37 theme cardiac 127:133 arg1 myocytes 135:142 cultured cardiac myocytes 118:142 cultured cardiac myocytes 118:142 The inhibition of N-glycosylation of glycoprotein 130 molecule abolishes STAT3 activation by IL-6 family cytokines in cultured cardiac myocytes. 25340554 5 38 theme inhibitory 891:900 arg1 factor 902:907 leukemia inhibitory factor 882:907 leukemia inhibitory factor 882:907 Tm treatment inhibited leukemia inhibitory factor (LIF)-mediated activation of STAT3 and ERK1/2. 25340554 8 39 theme downstream 1587:1596 arg1 signals 1598:1604 the downstream signals 1583:1604 the downstream signals 1583:1604 To exclude the possibility that Tm blocks LIF and IL-11 signals by inhibiting the glycosylation of their specific receptors, we investigated whether the stimulation with IL-6 plus soluble IL-6 receptor (sIL-6R) could transduce their signals in Tm-treated cardiomyocytes and found that this stimulation was unable to activate the downstream signals. 25340554 2 40 theme kinase 436:441 arg1 ERK 444:446 extracellular signal-regulated kinase (ERK)1/2 405:450 extracellular signal-regulated kinase (ERK)1/2 405:450 IL-6 cytokines bind to their specific receptors and activate glycoprotein 130 (gp130), a common receptor, followed by further activation of STAT3 and extracellular signal-regulated kinase (ERK)1/2 through janus kinases (JAKs); however the importance of glycosylation of gp130 remains to be elucidated in cardiac myocytes. 25340554 4 41 gly glycosylated 803:814 arg1 gp130 824:828 gp130 824:828 gp130 824:828 In cardiomyocytes, the treatment with Tm completely replaced the glycosylated form of gp130 with its unglycosylated one. 25340554 4 41 gly glycosylated 803:814 arg1 form 816:819 the glycosylated form 799:819 the glycosylated form of gp130 799:828 In cardiomyocytes, the treatment with Tm completely replaced the glycosylated form of gp130 with its unglycosylated one. 25340554 0 42 theme cultured 118:125 arg1 myocytes 135:142 cultured cardiac myocytes 118:142 cultured cardiac myocytes 118:142 The inhibition of N-glycosylation of glycoprotein 130 molecule abolishes STAT3 activation by IL-6 family cytokines in cultured cardiac myocytes. 25340554 5 43 dep -mediated 914:922 arg1 factor 902:907 leukemia inhibitory factor 882:907 leukemia inhibitory factor 882:907 Tm treatment inhibited leukemia inhibitory factor (LIF)-mediated activation of STAT3 and ERK1/2. 25340554 2 44 theme signal-regulated 419:434 arg1 ERK 444:446 extracellular signal-regulated kinase (ERK)1/2 405:450 extracellular signal-regulated kinase (ERK)1/2 405:450 IL-6 cytokines bind to their specific receptors and activate glycoprotein 130 (gp130), a common receptor, followed by further activation of STAT3 and extracellular signal-regulated kinase (ERK)1/2 through janus kinases (JAKs); however the importance of glycosylation of gp130 remains to be elucidated in cardiac myocytes. 25340554 0 45 theme glycoprotein 37:48 arg1 molecule 54:61 glycoprotein 130 molecule 37:61 glycoprotein 130 molecule 37:61 The inhibition of N-glycosylation of glycoprotein 130 molecule abolishes STAT3 activation by IL-6 family cytokines in cultured cardiac myocytes. 25340554 2 46 theme gp130 525:529 arg1 glycosylation 508:520 glycosylation 508:520 glycosylation of gp130 508:529 IL-6 cytokines bind to their specific receptors and activate glycoprotein 130 (gp130), a common receptor, followed by further activation of STAT3 and extracellular signal-regulated kinase (ERK)1/2 through janus kinases (JAKs); however the importance of glycosylation of gp130 remains to be elucidated in cardiac myocytes. 25340554 0 47 from activation 79:88 arg1 myocytes 135:142 cultured cardiac myocytes 118:142 cultured cardiac myocytes 118:142 The inhibition of N-glycosylation of glycoprotein 130 molecule abolishes STAT3 activation by IL-6 family cytokines in cultured cardiac myocytes. 25340554 2 48 theme IL-6 255:258 arg1 cytokines 260:268 IL-6 cytokines 255:268 IL-6 cytokines 255:268 IL-6 cytokines bind to their specific receptors and activate glycoprotein 130 (gp130), a common receptor, followed by further activation of STAT3 and extracellular signal-regulated kinase (ERK)1/2 through janus kinases (JAKs); however the importance of glycosylation of gp130 remains to be elucidated in cardiac myocytes. 25340554 2 49 theme further 373:379 arg1 activation 381:390 further activation 373:390 further activation of STAT3 and extracellular signal-regulated kinase (ERK)1/2 through janus kinases (JAKs) 373:479 IL-6 cytokines bind to their specific receptors and activate glycoprotein 130 (gp130), a common receptor, followed by further activation of STAT3 and extracellular signal-regulated kinase (ERK)1/2 through janus kinases (JAKs); however the importance of glycosylation of gp130 remains to be elucidated in cardiac myocytes. 25340554 2 50 theme extracellular 405:417 arg1 ERK 444:446 extracellular signal-regulated kinase (ERK)1/2 405:450 extracellular signal-regulated kinase (ERK)1/2 405:450 IL-6 cytokines bind to their specific receptors and activate glycoprotein 130 (gp130), a common receptor, followed by further activation of STAT3 and extracellular signal-regulated kinase (ERK)1/2 through janus kinases (JAKs); however the importance of glycosylation of gp130 remains to be elucidated in cardiac myocytes. 25340554 2 51 theme STAT3 395:399 arg1 activation 381:390 further activation 373:390 further activation of STAT3 and extracellular signal-regulated kinase (ERK)1/2 through janus kinases (JAKs) 373:479 IL-6 cytokines bind to their specific receptors and activate glycoprotein 130 (gp130), a common receptor, followed by further activation of STAT3 and extracellular signal-regulated kinase (ERK)1/2 through janus kinases (JAKs); however the importance of glycosylation of gp130 remains to be elucidated in cardiac myocytes. 25340554 8 52 theme Tm-treated 1502:1511 arg1 cardiomyocytes 1513:1526 Tm-treated cardiomyocytes 1502:1526 Tm-treated cardiomyocytes 1502:1526 To exclude the possibility that Tm blocks LIF and IL-11 signals by inhibiting the glycosylation of their specific receptors, we investigated whether the stimulation with IL-6 plus soluble IL-6 receptor (sIL-6R) could transduce their signals in Tm-treated cardiomyocytes and found that this stimulation was unable to activate the downstream signals. 25340554 0 53 theme N-glycosylation 18:32 arg1 inhibition 4:13 The inhibition 0:13 The inhibition of N-glycosylation of glycoprotein 130 molecule 0:61 The inhibition of N-glycosylation of glycoprotein 130 molecule abolishes STAT3 activation by IL-6 family cytokines in cultured cardiac myocytes. 25340554 7 54 theme endogenous 1227:1236 arg1 inhibitors 1238:1247 endogenous inhibitors 1227:1247 endogenous inhibitors of JAKs 1227:1255 Interestingly, Tm inhibited the activation of JAKs 1 and 2, without influencing the expression of suppressor of cytokine signalings (SOCSs) and protein-tyrosine phosphatase 1B (PTP1B), which are endogenous inhibitors of JAKs. 25340554 7 54 theme endogenous 1227:1236 arg1 expression 1116:1125 the expression 1112:1125 the expression 1112:1125 Interestingly, Tm inhibited the activation of JAKs 1 and 2, without influencing the expression of suppressor of cytokine signalings (SOCSs) and protein-tyrosine phosphatase 1B (PTP1B), which are endogenous inhibitors of JAKs. 25340554 2 55 theme janus 460:464 arg1 JAKs 475:478 JAKs 475:478 JAKs 475:478 IL-6 cytokines bind to their specific receptors and activate glycoprotein 130 (gp130), a common receptor, followed by further activation of STAT3 and extracellular signal-regulated kinase (ERK)1/2 through janus kinases (JAKs); however the importance of glycosylation of gp130 remains to be elucidated in cardiac myocytes. 25340554 2 55 theme janus 460:464 arg1 kinases 466:472 janus kinases 460:472 janus kinases (JAKs) 460:479 IL-6 cytokines bind to their specific receptors and activate glycoprotein 130 (gp130), a common receptor, followed by further activation of STAT3 and extracellular signal-regulated kinase (ERK)1/2 through janus kinases (JAKs); however the importance of glycosylation of gp130 remains to be elucidated in cardiac myocytes. 25340554 2 56 theme glycosylation 508:520 arg1 importance 494:503 the importance 490:503 the importance of glycosylation of gp130 490:529 IL-6 cytokines bind to their specific receptors and activate glycoprotein 130 (gp130), a common receptor, followed by further activation of STAT3 and extracellular signal-regulated kinase (ERK)1/2 through janus kinases (JAKs); however the importance of glycosylation of gp130 remains to be elucidated in cardiac myocytes. 25340554 2 57 theme cardiac 559:565 arg1 myocytes 567:574 cardiac myocytes 559:574 cardiac myocytes 559:574 IL-6 cytokines bind to their specific receptors and activate glycoprotein 130 (gp130), a common receptor, followed by further activation of STAT3 and extracellular signal-regulated kinase (ERK)1/2 through janus kinases (JAKs); however the importance of glycosylation of gp130 remains to be elucidated in cardiac myocytes. 25340554 3 58 theme biological 608:617 arg1 significance 619:630 the biological significance 604:630 the biological significance of gp130 glycosylation using tunicamycin (Tm), an inhibitor of enzyme involved in N-linked glycosylation 604:735 In this study, we examined the biological significance of gp130 glycosylation using tunicamycin (Tm), an inhibitor of enzyme involved in N-linked glycosylation. 25340554 4 59 theme glycosylated 803:814 arg1 form 816:819 the glycosylated form 799:819 the glycosylated form of gp130 799:828 In cardiomyocytes, the treatment with Tm completely replaced the glycosylated form of gp130 with its unglycosylated one. 25340554 2 60 theme common 344:349 arg1 glycoprotein 316:327 glycoprotein 130 316:331 glycoprotein 130 (gp130) 316:339 IL-6 cytokines bind to their specific receptors and activate glycoprotein 130 (gp130), a common receptor, followed by further activation of STAT3 and extracellular signal-regulated kinase (ERK)1/2 through janus kinases (JAKs); however the importance of glycosylation of gp130 remains to be elucidated in cardiac myocytes. 25340554 2 60 theme common 344:349 arg1 receptor 351:358 a common receptor 342:358 a common receptor 342:358 IL-6 cytokines bind to their specific receptors and activate glycoprotein 130 (gp130), a common receptor, followed by further activation of STAT3 and extracellular signal-regulated kinase (ERK)1/2 through janus kinases (JAKs); however the importance of glycosylation of gp130 remains to be elucidated in cardiac myocytes. 25340554 7 61 theme 2 1089:1089 arg1 activation 1064:1073 the activation 1060:1073 the activation of JAKs 1 and 2 1060:1089 Interestingly, Tm inhibited the activation of JAKs 1 and 2, without influencing the expression of suppressor of cytokine signalings (SOCSs) and protein-tyrosine phosphatase 1B (PTP1B), which are endogenous inhibitors of JAKs. 25340554 3 62 theme using 655:659 arg1 inhibitor 682:690 an inhibitor 679:690 an inhibitor of enzyme involved in N-linked glycosylation 679:735 In this study, we examined the biological significance of gp130 glycosylation using tunicamycin (Tm), an inhibitor of enzyme involved in N-linked glycosylation. 25340554 3 62 theme using 655:659 arg1 Tm 674:675 Tm 674:675 Tm 674:675 In this study, we examined the biological significance of gp130 glycosylation using tunicamycin (Tm), an inhibitor of enzyme involved in N-linked glycosylation. 25340554 3 62 theme using 655:659 arg1 tunicamycin 661:671 gp130 glycosylation using tunicamycin 635:671 gp130 glycosylation using tunicamycin (Tm) 635:676 In this study, we examined the biological significance of gp130 glycosylation using tunicamycin (Tm), an inhibitor of enzyme involved in N-linked glycosylation. 25340554 8 63 theme receptors 1372:1380 arg1 glycosylation 1340:1352 the glycosylation 1336:1352 the glycosylation of their specific receptors 1336:1380 To exclude the possibility that Tm blocks LIF and IL-11 signals by inhibiting the glycosylation of their specific receptors, we investigated whether the stimulation with IL-6 plus soluble IL-6 receptor (sIL-6R) could transduce their signals in Tm-treated cardiomyocytes and found that this stimulation was unable to activate the downstream signals. 25340554 9 64 theme signal 1690:1695 arg1 transduction 1697:1708 signal transduction 1690:1708 signal transduction of IL-6 family cytokines in cardiomyocytes 1690:1751 Collectively, these findings indicate that glycosylation of gp130 is essential for signal transduction of IL-6 family cytokines in cardiomyocytes. 25340554 3 65 theme tunicamycin 661:671 arg1 significance 619:630 the biological significance 604:630 the biological significance of gp130 glycosylation using tunicamycin (Tm), an inhibitor of enzyme involved in N-linked glycosylation 604:735 In this study, we examined the biological significance of gp130 glycosylation using tunicamycin (Tm), an inhibitor of enzyme involved in N-linked glycosylation. 25340554 1 66 theme pathological 232:243 arg1 stresses 245:252 pathological stresses 232:252 pathological stresses 232:252 Interleukin-6 (IL-6) family cytokines play important roles in cardioprotection against pathological stresses. 25340554 3 67 theme gp130 635:639 arg1 inhibitor 682:690 an inhibitor 679:690 an inhibitor of enzyme involved in N-linked glycosylation 679:735 In this study, we examined the biological significance of gp130 glycosylation using tunicamycin (Tm), an inhibitor of enzyme involved in N-linked glycosylation. 25340554 3 67 theme gp130 635:639 arg1 Tm 674:675 Tm 674:675 Tm 674:675 In this study, we examined the biological significance of gp130 glycosylation using tunicamycin (Tm), an inhibitor of enzyme involved in N-linked glycosylation. 25340554 3 67 theme gp130 635:639 arg1 tunicamycin 661:671 gp130 glycosylation using tunicamycin 635:671 gp130 glycosylation using tunicamycin (Tm) 635:676 In this study, we examined the biological significance of gp130 glycosylation using tunicamycin (Tm), an inhibitor of enzyme involved in N-linked glycosylation. 25340554 0 68 gly glycoprotein 37:48 arg1 glycoprotein 37:48 glycoprotein 130 molecule 37:61 glycoprotein 130 molecule 37:61 The inhibition of N-glycosylation of glycoprotein 130 molecule abolishes STAT3 activation by IL-6 family cytokines in cultured cardiac myocytes. 25340554 0 69 theme STAT3 73:77 arg1 activation 79:88 STAT3 activation 73:88 STAT3 activation by IL-6 family cytokines in cultured cardiac myocytes 73:142 The inhibition of N-glycosylation of glycoprotein 130 molecule abolishes STAT3 activation by IL-6 family cytokines in cultured cardiac myocytes. 25340554 3 70 theme glycosylation 641:653 arg1 inhibitor 682:690 an inhibitor 679:690 an inhibitor of enzyme involved in N-linked glycosylation 679:735 In this study, we examined the biological significance of gp130 glycosylation using tunicamycin (Tm), an inhibitor of enzyme involved in N-linked glycosylation. 25340554 3 70 theme glycosylation 641:653 arg1 Tm 674:675 Tm 674:675 Tm 674:675 In this study, we examined the biological significance of gp130 glycosylation using tunicamycin (Tm), an inhibitor of enzyme involved in N-linked glycosylation. 25340554 3 70 theme glycosylation 641:653 arg1 tunicamycin 661:671 gp130 glycosylation using tunicamycin 635:671 gp130 glycosylation using tunicamycin (Tm) 635:676 In this study, we examined the biological significance of gp130 glycosylation using tunicamycin (Tm), an inhibitor of enzyme involved in N-linked glycosylation. 25340554 8 71 theme specific 1363:1370 arg1 receptors 1372:1380 their specific receptors 1357:1380 their specific receptors 1357:1380 To exclude the possibility that Tm blocks LIF and IL-11 signals by inhibiting the glycosylation of their specific receptors, we investigated whether the stimulation with IL-6 plus soluble IL-6 receptor (sIL-6R) could transduce their signals in Tm-treated cardiomyocytes and found that this stimulation was unable to activate the downstream signals. 25340554 1 72 theme Interleukin-6 145:157 arg1 cytokines 173:181 Interleukin-6 (IL-6) family cytokines 145:181 Interleukin-6 (IL-6) family cytokines 145:181 Interleukin-6 (IL-6) family cytokines play important roles in cardioprotection against pathological stresses. 25340554 0 73 theme molecule 54:61 arg1 inhibition 4:13 The inhibition 0:13 The inhibition of N-glycosylation of glycoprotein 130 molecule 0:61 The inhibition of N-glycosylation of glycoprotein 130 molecule abolishes STAT3 activation by IL-6 family cytokines in cultured cardiac myocytes. 25340554 3 74 link N-linked 714:721 arg1 glycosylation 723:735 N-linked glycosylation 714:735 N-linked glycosylation 714:735 In this study, we examined the biological significance of gp130 glycosylation using tunicamycin (Tm), an inhibitor of enzyme involved in N-linked glycosylation. 25340554 8 75 with stimulation 1411:1421 arg1 IL-6 1428:1431 IL-6 1428:1431 IL-6 1428:1431 To exclude the possibility that Tm blocks LIF and IL-11 signals by inhibiting the glycosylation of their specific receptors, we investigated whether the stimulation with IL-6 plus soluble IL-6 receptor (sIL-6R) could transduce their signals in Tm-treated cardiomyocytes and found that this stimulation was unable to activate the downstream signals. 25340554 8 75 with stimulation 1411:1421 arg1 sIL-6R 1461:1466 sIL-6R 1461:1466 sIL-6R 1461:1466 To exclude the possibility that Tm blocks LIF and IL-11 signals by inhibiting the glycosylation of their specific receptors, we investigated whether the stimulation with IL-6 plus soluble IL-6 receptor (sIL-6R) could transduce their signals in Tm-treated cardiomyocytes and found that this stimulation was unable to activate the downstream signals. 25340554 8 75 with stimulation 1411:1421 arg1 receptor 1451:1458 soluble IL-6 receptor 1438:1458 soluble IL-6 receptor (sIL-6R) 1438:1467 To exclude the possibility that Tm blocks LIF and IL-11 signals by inhibiting the glycosylation of their specific receptors, we investigated whether the stimulation with IL-6 plus soluble IL-6 receptor (sIL-6R) could transduce their signals in Tm-treated cardiomyocytes and found that this stimulation was unable to activate the downstream signals. 25340554 7 76 theme signalings 1153:1162 arg1 suppressor 1130:1139 suppressor 1130:1139 suppressor of cytokine signalings (SOCSs) and protein-tyrosine phosphatase 1B (PTP1B) 1130:1214 Interestingly, Tm inhibited the activation of JAKs 1 and 2, without influencing the expression of suppressor of cytokine signalings (SOCSs) and protein-tyrosine phosphatase 1B (PTP1B), which are endogenous inhibitors of JAKs. 25030055 7 0 theme Reserve 1499:1505 arg1 strain 1507:1512 the Western Reserve strain 1487:1512 the Western Reserve strain 1487:1512 Recombinant vaccinia viruses expressing FLAG-tagged glycosylated VCP (FLAG-VCPg) and nonglycosylated VCP (FLAG-VCP) were constructed based on the Western Reserve strain. 25030055 2 1 theme smallpox 334:341 arg1 vaccine 343:349 an attenuated smallpox vaccine 320:349 an attenuated smallpox vaccine 320:349 Previously, we reported that an attenuated smallpox vaccine, LC16m8, which was derived from the Lister strain of vaccinia virus (VV-Lister), expressed a glycosylated form of VCP, whereas published sequence data at that time indicated that the VV-Lister VCP has no motif for N-linked glycosylation. 25030055 2 1 theme smallpox 334:341 arg1 LC16m8 352:357 LC16m8 352:357 LC16m8 352:357 Previously, we reported that an attenuated smallpox vaccine, LC16m8, which was derived from the Lister strain of vaccinia virus (VV-Lister), expressed a glycosylated form of VCP, whereas published sequence data at that time indicated that the VV-Lister VCP has no motif for N-linked glycosylation. 25030055 6 2 theme purified 1177:1184 arg1 VCP 1186:1188 partially purified VCP 1167:1188 partially purified VCP from the isolates 1167:1206 Individual Lister virus clones expressing either the glycosylated VCP or the nonglycosylated species were isolated, and partially purified VCP from the isolates were found to be functional equivalents in binding human C3b and C4b complement proteins and inhibiting hemolysis and in immunogenicity. 25030055 2 3 link N-linked 565:572 arg1 glycosylation 574:586 N-linked glycosylation 565:586 N-linked glycosylation 565:586 Previously, we reported that an attenuated smallpox vaccine, LC16m8, which was derived from the Lister strain of vaccinia virus (VV-Lister), expressed a glycosylated form of VCP, whereas published sequence data at that time indicated that the VV-Lister VCP has no motif for N-linked glycosylation. 25030055 6 4 theme human 1259:1263 arg1 proteins 1288:1295 human C3b and C4b complement proteins 1259:1295 human C3b and C4b complement proteins 1259:1295 Individual Lister virus clones expressing either the glycosylated VCP or the nonglycosylated species were isolated, and partially purified VCP from the isolates were found to be functional equivalents in binding human C3b and C4b complement proteins and inhibiting hemolysis and in immunogenicity. 25030055 1 5 theme classic 246:252 arg1 pathways 281:288 the classic and alternative complement pathways 242:288 the classic and alternative complement pathways 242:288 The vaccinia virus complement control protein (VCP) is a secreted viral protein that binds the C3b and C4b complement components and inhibits the classic and alternative complement pathways. 25030055 4 6 theme Expression 788:797 arg1 analysis 799:806 Expression analysis 788:806 Expression analysis 788:806 Expression analysis indicated that VV-Lister contains substrains expressing glycosylated VCP and substrains expressing nonglycosylated VCP. 25030055 7 7 theme nonglycosylated 1430:1444 arg1 VCP 1446:1448 nonglycosylated VCP 1430:1448 nonglycosylated VCP (FLAG-VCP) 1430:1459 Recombinant vaccinia viruses expressing FLAG-tagged glycosylated VCP (FLAG-VCPg) and nonglycosylated VCP (FLAG-VCP) were constructed based on the Western Reserve strain. 25030055 7 7 theme nonglycosylated 1430:1444 arg1 FLAG-VCP 1451:1458 FLAG-VCP 1451:1458 FLAG-VCP 1451:1458 Recombinant vaccinia viruses expressing FLAG-tagged glycosylated VCP (FLAG-VCPg) and nonglycosylated VCP (FLAG-VCP) were constructed based on the Western Reserve strain. 25030055 1 8 theme secreted 157:164 arg1 protein 172:178 a secreted viral protein 155:178 a secreted viral protein that binds the C3b and C4b complement components and inhibits the classic and alternative complement pathways 155:288 The vaccinia virus complement control protein (VCP) is a secreted viral protein that binds the C3b and C4b complement components and inhibits the classic and alternative complement pathways. 25030055 1 8 theme secreted 157:164 arg1 protein 138:144 The vaccinia virus complement control protein 100:144 The vaccinia virus complement control protein (VCP) 100:150 The vaccinia virus complement control protein (VCP) is a secreted viral protein that binds the C3b and C4b complement components and inhibits the classic and alternative complement pathways. 25030055 6 9 theme functional 1225:1234 arg1 equivalents 1236:1246 functional equivalents 1225:1246 functional equivalents 1225:1246 Individual Lister virus clones expressing either the glycosylated VCP or the nonglycosylated species were isolated, and partially purified VCP from the isolates were found to be functional equivalents in binding human C3b and C4b complement proteins and inhibiting hemolysis and in immunogenicity. 25030055 3 10 gly glycosylated 770:781 arg1 VCP 783:785 the glycosylated VCP 766:785 the glycosylated VCP 766:785 We were interested in determining whether the glycosylation of VCP impairs its biological activity, possibly contributing to the attenuation of LC16m8, and the likely origin of the glycosylated VCP. 25030055 7 11 theme glycosylated 1397:1408 arg1 FLAG-VCPg 1415:1423 FLAG-VCPg 1415:1423 FLAG-VCPg 1415:1423 Recombinant vaccinia viruses expressing FLAG-tagged glycosylated VCP (FLAG-VCPg) and nonglycosylated VCP (FLAG-VCP) were constructed based on the Western Reserve strain. 25030055 7 11 theme glycosylated 1397:1408 arg1 VCP 1410:1412 FLAG-tagged glycosylated VCP 1385:1412 FLAG-tagged glycosylated VCP (FLAG-VCPg) 1385:1424 Recombinant vaccinia viruses expressing FLAG-tagged glycosylated VCP (FLAG-VCPg) and nonglycosylated VCP (FLAG-VCP) were constructed based on the Western Reserve strain. 25030055 3 12 theme LC16m8 733:738 arg1 origin 756:761 the likely origin 745:761 the likely origin of the glycosylated VCP 745:785 We were interested in determining whether the glycosylation of VCP impairs its biological activity, possibly contributing to the attenuation of LC16m8, and the likely origin of the glycosylated VCP. 25030055 3 12 theme LC16m8 733:738 arg1 attenuation 718:728 the attenuation 714:728 the attenuation of LC16m8 714:738 We were interested in determining whether the glycosylation of VCP impairs its biological activity, possibly contributing to the attenuation of LC16m8, and the likely origin of the glycosylated VCP. 25030055 9 13 gly glycosylation 1635:1647 arg1 VCP 1691:1693 VCP 1691:1693 VCP 1691:1693 Our data suggest that glycosylation did not affect the biological activity of VCP and thus may not have contributed to the attenuation of LC16m8. 25030055 9 13 gly glycosylation 1635:1647 arg1 LC16m8 1751:1756 LC16m8 1751:1756 LC16m8 1751:1756 Our data suggest that glycosylation did not affect the biological activity of VCP and thus may not have contributed to the attenuation of LC16m8. 25030055 1 14 theme C3b 195:197 arg1 components 218:227 the C3b and C4b complement components 191:227 the C3b and C4b complement components 191:227 The vaccinia virus complement control protein (VCP) is a secreted viral protein that binds the C3b and C4b complement components and inhibits the classic and alternative complement pathways. 25030055 4 15 theme glycosylated 864:875 arg1 VCP 877:879 glycosylated VCP 864:879 glycosylated VCP 864:879 Expression analysis indicated that VV-Lister contains substrains expressing glycosylated VCP and substrains expressing nonglycosylated VCP. 25030055 1 16 theme complement 119:128 arg1 VCP 147:149 VCP 147:149 VCP 147:149 The vaccinia virus complement control protein (VCP) is a secreted viral protein that binds the C3b and C4b complement components and inhibits the classic and alternative complement pathways. 25030055 1 16 theme complement 119:128 arg1 protein 138:144 The vaccinia virus complement control protein 100:144 The vaccinia virus complement control protein (VCP) 100:150 The vaccinia virus complement control protein (VCP) is a secreted viral protein that binds the C3b and C4b complement components and inhibits the classic and alternative complement pathways. 25030055 1 16 theme complement 119:128 arg1 protein 172:178 a secreted viral protein 155:178 a secreted viral protein that binds the C3b and C4b complement components and inhibits the classic and alternative complement pathways 155:288 The vaccinia virus complement control protein (VCP) is a secreted viral protein that binds the C3b and C4b complement components and inhibits the classic and alternative complement pathways. 25030055 7 17 theme vaccinia 1357:1364 arg1 viruses 1366:1372 Recombinant vaccinia viruses 1345:1372 Recombinant vaccinia viruses expressing FLAG-tagged glycosylated VCP (FLAG-VCPg) and nonglycosylated VCP (FLAG-VCP) 1345:1459 Recombinant vaccinia viruses expressing FLAG-tagged glycosylated VCP (FLAG-VCPg) and nonglycosylated VCP (FLAG-VCP) were constructed based on the Western Reserve strain. 25030055 3 18 theme likely 749:754 arg1 origin 756:761 the likely origin 745:761 the likely origin of the glycosylated VCP 745:785 We were interested in determining whether the glycosylation of VCP impairs its biological activity, possibly contributing to the attenuation of LC16m8, and the likely origin of the glycosylated VCP. 25030055 6 19 theme complement 1277:1286 arg1 proteins 1288:1295 human C3b and C4b complement proteins 1259:1295 human C3b and C4b complement proteins 1259:1295 Individual Lister virus clones expressing either the glycosylated VCP or the nonglycosylated species were isolated, and partially purified VCP from the isolates were found to be functional equivalents in binding human C3b and C4b complement proteins and inhibiting hemolysis and in immunogenicity. 25030055 5 20 theme nonglycosylated 1026:1040 arg1 VCP 1042:1044 nonglycosylated VCP 1026:1044 nonglycosylated VCP 1026:1044 Other strains of smallpox vaccine, as well as laboratory strains of vaccinia virus, all expressed nonglycosylated VCP. 25030055 1 21 theme control 130:136 arg1 VCP 147:149 VCP 147:149 VCP 147:149 The vaccinia virus complement control protein (VCP) is a secreted viral protein that binds the C3b and C4b complement components and inhibits the classic and alternative complement pathways. 25030055 1 21 theme control 130:136 arg1 protein 138:144 The vaccinia virus complement control protein 100:144 The vaccinia virus complement control protein (VCP) 100:150 The vaccinia virus complement control protein (VCP) is a secreted viral protein that binds the C3b and C4b complement components and inhibits the classic and alternative complement pathways. 25030055 1 21 theme control 130:136 arg1 protein 172:178 a secreted viral protein 155:178 a secreted viral protein that binds the C3b and C4b complement components and inhibits the classic and alternative complement pathways 155:288 The vaccinia virus complement control protein (VCP) is a secreted viral protein that binds the C3b and C4b complement components and inhibits the classic and alternative complement pathways. 25030055 5 22 gly nonglycosylated 1026:1040 arg1 VCP 1042:1044 nonglycosylated VCP 1026:1044 nonglycosylated VCP 1026:1044 Other strains of smallpox vaccine, as well as laboratory strains of vaccinia virus, all expressed nonglycosylated VCP. 25030055 0 23 theme lister 67:72 arg1 strain 74:79 the lister strain 63:79 the lister strain of vaccinia virus 63:97 Glycosylated and nonglycosylated complement control protein of the lister strain of vaccinia virus. 25030055 4 24 gly glycosylated 864:875 arg1 VCP 877:879 glycosylated VCP 864:879 glycosylated VCP 864:879 Expression analysis indicated that VV-Lister contains substrains expressing glycosylated VCP and substrains expressing nonglycosylated VCP. 25030055 4 25 contain contains 833:840 arg2 substrains 842:851 substrains 842:851 substrains expressing glycosylated VCP 842:879 Expression analysis indicated that VV-Lister contains substrains expressing glycosylated VCP and substrains expressing nonglycosylated VCP. 25030055 4 25 contain contains 833:840 arg1 VV-Lister 823:831 VV-Lister 823:831 VV-Lister 823:831 Expression analysis indicated that VV-Lister contains substrains expressing glycosylated VCP and substrains expressing nonglycosylated VCP. 25030055 4 25 contain contains 833:840 arg2 substrains 885:894 substrains 885:894 substrains expressing nonglycosylated VCP 885:925 Expression analysis indicated that VV-Lister contains substrains expressing glycosylated VCP and substrains expressing nonglycosylated VCP. 25030055 2 26 theme glycosylated 444:455 arg1 form 457:460 a glycosylated form 442:460 a glycosylated form of VCP 442:467 Previously, we reported that an attenuated smallpox vaccine, LC16m8, which was derived from the Lister strain of vaccinia virus (VV-Lister), expressed a glycosylated form of VCP, whereas published sequence data at that time indicated that the VV-Lister VCP has no motif for N-linked glycosylation. 25030055 3 27 theme glycosylated 770:781 arg1 VCP 783:785 the glycosylated VCP 766:785 the glycosylated VCP 766:785 We were interested in determining whether the glycosylation of VCP impairs its biological activity, possibly contributing to the attenuation of LC16m8, and the likely origin of the glycosylated VCP. 25030055 2 28 theme published 478:486 arg1 data 497:500 published sequence data 478:500 published sequence data at that time 478:513 Previously, we reported that an attenuated smallpox vaccine, LC16m8, which was derived from the Lister strain of vaccinia virus (VV-Lister), expressed a glycosylated form of VCP, whereas published sequence data at that time indicated that the VV-Lister VCP has no motif for N-linked glycosylation. 25030055 8 29 theme Purified 1515:1522 arg1 FLAG-VCP 1524:1531 FLAG-VCP 1524:1531 FLAG-VCP 1524:1531 Purified FLAG-VCP and FLAG-VCPg bind human C3b and C4b and blocked complement-mediated hemolysis. 25030055 2 30 gly glycosylated 444:455 arg1 form 457:460 a glycosylated form 442:460 a glycosylated form of VCP 442:467 Previously, we reported that an attenuated smallpox vaccine, LC16m8, which was derived from the Lister strain of vaccinia virus (VV-Lister), expressed a glycosylated form of VCP, whereas published sequence data at that time indicated that the VV-Lister VCP has no motif for N-linked glycosylation. 25030055 2 30 gly glycosylated 444:455 arg1 VCP 465:467 VCP 465:467 VCP 465:467 Previously, we reported that an attenuated smallpox vaccine, LC16m8, which was derived from the Lister strain of vaccinia virus (VV-Lister), expressed a glycosylated form of VCP, whereas published sequence data at that time indicated that the VV-Lister VCP has no motif for N-linked glycosylation. 25030055 0 31 theme virus 93:97 arg1 strain 74:79 the lister strain 63:79 the lister strain of vaccinia virus 63:97 Glycosylated and nonglycosylated complement control protein of the lister strain of vaccinia virus. 25030055 5 32 theme vaccine 954:960 arg1 strains 934:940 Other strains 928:940 Other strains of smallpox vaccine 928:960 Other strains of smallpox vaccine, as well as laboratory strains of vaccinia virus, all expressed nonglycosylated VCP. 25030055 5 32 theme vaccine 954:960 arg1 strains 985:991 laboratory strains 974:991 laboratory strains of vaccinia virus 974:1009 Other strains of smallpox vaccine, as well as laboratory strains of vaccinia virus, all expressed nonglycosylated VCP. 25030055 6 33 theme Lister 1058:1063 arg1 clones 1071:1076 Individual Lister virus clones 1047:1076 Individual Lister virus clones expressing either the glycosylated VCP or the nonglycosylated species 1047:1146 Individual Lister virus clones expressing either the glycosylated VCP or the nonglycosylated species were isolated, and partially purified VCP from the isolates were found to be functional equivalents in binding human C3b and C4b complement proteins and inhibiting hemolysis and in immunogenicity. 25030055 6 34 gly glycosylated 1100:1111 arg1 VCP 1113:1115 the glycosylated VCP 1096:1115 the glycosylated VCP 1096:1115 Individual Lister virus clones expressing either the glycosylated VCP or the nonglycosylated species were isolated, and partially purified VCP from the isolates were found to be functional equivalents in binding human C3b and C4b complement proteins and inhibiting hemolysis and in immunogenicity. 25030055 5 35 theme Other 928:932 arg1 strains 934:940 Other strains 928:940 Other strains of smallpox vaccine 928:960 Other strains of smallpox vaccine, as well as laboratory strains of vaccinia virus, all expressed nonglycosylated VCP. 25030055 2 36 theme vaccinia 404:411 arg1 virus 413:417 vaccinia virus 404:417 vaccinia virus (VV-Lister) 404:429 Previously, we reported that an attenuated smallpox vaccine, LC16m8, which was derived from the Lister strain of vaccinia virus (VV-Lister), expressed a glycosylated form of VCP, whereas published sequence data at that time indicated that the VV-Lister VCP has no motif for N-linked glycosylation. 25030055 2 36 theme vaccinia 404:411 arg1 VV-Lister 420:428 VV-Lister 420:428 VV-Lister 420:428 Previously, we reported that an attenuated smallpox vaccine, LC16m8, which was derived from the Lister strain of vaccinia virus (VV-Lister), expressed a glycosylated form of VCP, whereas published sequence data at that time indicated that the VV-Lister VCP has no motif for N-linked glycosylation. 25030055 1 37 theme complement 270:279 arg1 pathways 281:288 the classic and alternative complement pathways 242:288 the classic and alternative complement pathways 242:288 The vaccinia virus complement control protein (VCP) is a secreted viral protein that binds the C3b and C4b complement components and inhibits the classic and alternative complement pathways. 25030055 1 38 theme vaccinia 104:111 arg1 VCP 147:149 VCP 147:149 VCP 147:149 The vaccinia virus complement control protein (VCP) is a secreted viral protein that binds the C3b and C4b complement components and inhibits the classic and alternative complement pathways. 25030055 1 38 theme vaccinia 104:111 arg1 protein 138:144 The vaccinia virus complement control protein 100:144 The vaccinia virus complement control protein (VCP) 100:150 The vaccinia virus complement control protein (VCP) is a secreted viral protein that binds the C3b and C4b complement components and inhibits the classic and alternative complement pathways. 25030055 1 38 theme vaccinia 104:111 arg1 protein 172:178 a secreted viral protein 155:178 a secreted viral protein that binds the C3b and C4b complement components and inhibits the classic and alternative complement pathways 155:288 The vaccinia virus complement control protein (VCP) is a secreted viral protein that binds the C3b and C4b complement components and inhibits the classic and alternative complement pathways. 25030055 0 39 theme control 44:50 arg1 protein 52:58 control protein 44:58 control protein of the lister strain of vaccinia virus 44:97 Glycosylated and nonglycosylated complement control protein of the lister strain of vaccinia virus. 25030055 5 40 theme vaccinia 996:1003 arg1 virus 1005:1009 vaccinia virus 996:1009 vaccinia virus 996:1009 Other strains of smallpox vaccine, as well as laboratory strains of vaccinia virus, all expressed nonglycosylated VCP. 25030055 10 41 theme glycosylated 1852:1863 arg1 VCP 1865:1867 glycosylated VCP 1852:1867 glycosylated VCP 1852:1867 In addition, the LC16m8 virus likely originated from a substrain of VV-Lister that expresses glycosylated VCP. 25030055 2 42 theme attenuated 323:332 arg1 vaccine 343:349 an attenuated smallpox vaccine 320:349 an attenuated smallpox vaccine 320:349 Previously, we reported that an attenuated smallpox vaccine, LC16m8, which was derived from the Lister strain of vaccinia virus (VV-Lister), expressed a glycosylated form of VCP, whereas published sequence data at that time indicated that the VV-Lister VCP has no motif for N-linked glycosylation. 25030055 2 42 theme attenuated 323:332 arg1 LC16m8 352:357 LC16m8 352:357 LC16m8 352:357 Previously, we reported that an attenuated smallpox vaccine, LC16m8, which was derived from the Lister strain of vaccinia virus (VV-Lister), expressed a glycosylated form of VCP, whereas published sequence data at that time indicated that the VV-Lister VCP has no motif for N-linked glycosylation. 25030055 3 43 gly glycosylation 635:647 arg1 VCP 652:654 VCP 652:654 VCP 652:654 We were interested in determining whether the glycosylation of VCP impairs its biological activity, possibly contributing to the attenuation of LC16m8, and the likely origin of the glycosylated VCP. 25030055 6 44 theme glycosylated 1100:1111 arg1 VCP 1113:1115 the glycosylated VCP 1096:1115 the glycosylated VCP 1096:1115 Individual Lister virus clones expressing either the glycosylated VCP or the nonglycosylated species were isolated, and partially purified VCP from the isolates were found to be functional equivalents in binding human C3b and C4b complement proteins and inhibiting hemolysis and in immunogenicity. 25030055 1 45 theme complement 207:216 arg1 components 218:227 the C3b and C4b complement components 191:227 the C3b and C4b complement components 191:227 The vaccinia virus complement control protein (VCP) is a secreted viral protein that binds the C3b and C4b complement components and inhibits the classic and alternative complement pathways. 25030055 7 46 theme Western 1491:1497 arg1 strain 1507:1512 the Western Reserve strain 1487:1512 the Western Reserve strain 1487:1512 Recombinant vaccinia viruses expressing FLAG-tagged glycosylated VCP (FLAG-VCPg) and nonglycosylated VCP (FLAG-VCP) were constructed based on the Western Reserve strain. 25030055 6 47 theme C4b 1273:1275 arg1 proteins 1288:1295 human C3b and C4b complement proteins 1259:1295 human C3b and C4b complement proteins 1259:1295 Individual Lister virus clones expressing either the glycosylated VCP or the nonglycosylated species were isolated, and partially purified VCP from the isolates were found to be functional equivalents in binding human C3b and C4b complement proteins and inhibiting hemolysis and in immunogenicity. 25030055 9 48 theme biological 1668:1677 arg1 activity 1679:1686 the biological activity 1664:1686 the biological activity of VCP 1664:1693 Our data suggest that glycosylation did not affect the biological activity of VCP and thus may not have contributed to the attenuation of LC16m8. 25030055 2 49 from time 510:513 arg1 data 497:500 published sequence data 478:500 published sequence data at that time 478:513 Previously, we reported that an attenuated smallpox vaccine, LC16m8, which was derived from the Lister strain of vaccinia virus (VV-Lister), expressed a glycosylated form of VCP, whereas published sequence data at that time indicated that the VV-Lister VCP has no motif for N-linked glycosylation. 25030055 6 50 theme C3b 1265:1267 arg1 proteins 1288:1295 human C3b and C4b complement proteins 1259:1295 human C3b and C4b complement proteins 1259:1295 Individual Lister virus clones expressing either the glycosylated VCP or the nonglycosylated species were isolated, and partially purified VCP from the isolates were found to be functional equivalents in binding human C3b and C4b complement proteins and inhibiting hemolysis and in immunogenicity. 25030055 2 51 theme VV-Lister 534:542 arg1 VCP 544:546 the VV-Lister VCP 530:546 the VV-Lister VCP 530:546 Previously, we reported that an attenuated smallpox vaccine, LC16m8, which was derived from the Lister strain of vaccinia virus (VV-Lister), expressed a glycosylated form of VCP, whereas published sequence data at that time indicated that the VV-Lister VCP has no motif for N-linked glycosylation. 25030055 7 52 gly nonglycosylated 1430:1444 arg1 VCP 1446:1448 nonglycosylated VCP 1430:1448 nonglycosylated VCP (FLAG-VCP) 1430:1459 Recombinant vaccinia viruses expressing FLAG-tagged glycosylated VCP (FLAG-VCPg) and nonglycosylated VCP (FLAG-VCP) were constructed based on the Western Reserve strain. 25030055 7 52 gly nonglycosylated 1430:1444 arg1 FLAG-VCP 1451:1458 FLAG-VCP 1451:1458 FLAG-VCP 1451:1458 Recombinant vaccinia viruses expressing FLAG-tagged glycosylated VCP (FLAG-VCPg) and nonglycosylated VCP (FLAG-VCP) were constructed based on the Western Reserve strain. 25030055 2 53 theme N-linked 565:572 arg1 glycosylation 574:586 N-linked glycosylation 565:586 N-linked glycosylation 565:586 Previously, we reported that an attenuated smallpox vaccine, LC16m8, which was derived from the Lister strain of vaccinia virus (VV-Lister), expressed a glycosylated form of VCP, whereas published sequence data at that time indicated that the VV-Lister VCP has no motif for N-linked glycosylation. 25030055 3 54 theme biological 668:677 arg1 activity 679:686 its biological activity 664:686 its biological activity 664:686 We were interested in determining whether the glycosylation of VCP impairs its biological activity, possibly contributing to the attenuation of LC16m8, and the likely origin of the glycosylated VCP. 25030055 1 55 theme viral 166:170 arg1 protein 172:178 a secreted viral protein 155:178 a secreted viral protein that binds the C3b and C4b complement components and inhibits the classic and alternative complement pathways 155:288 The vaccinia virus complement control protein (VCP) is a secreted viral protein that binds the C3b and C4b complement components and inhibits the classic and alternative complement pathways. 25030055 1 55 theme viral 166:170 arg1 protein 138:144 The vaccinia virus complement control protein 100:144 The vaccinia virus complement control protein (VCP) 100:150 The vaccinia virus complement control protein (VCP) is a secreted viral protein that binds the C3b and C4b complement components and inhibits the classic and alternative complement pathways. 25030055 6 56 gly nonglycosylated 1124:1138 arg1 species 1140:1146 the nonglycosylated species 1120:1146 the nonglycosylated species 1120:1146 Individual Lister virus clones expressing either the glycosylated VCP or the nonglycosylated species were isolated, and partially purified VCP from the isolates were found to be functional equivalents in binding human C3b and C4b complement proteins and inhibiting hemolysis and in immunogenicity. 25030055 10 57 theme LC16m8 1776:1781 arg1 virus 1783:1787 the LC16m8 virus 1772:1787 the LC16m8 virus 1772:1787 In addition, the LC16m8 virus likely originated from a substrain of VV-Lister that expresses glycosylated VCP. 25030055 6 58 theme nonglycosylated 1124:1138 arg1 species 1140:1146 the nonglycosylated species 1120:1146 the nonglycosylated species 1120:1146 Individual Lister virus clones expressing either the glycosylated VCP or the nonglycosylated species were isolated, and partially purified VCP from the isolates were found to be functional equivalents in binding human C3b and C4b complement proteins and inhibiting hemolysis and in immunogenicity. 25030055 10 59 gly glycosylated 1852:1863 arg1 VCP 1865:1867 glycosylated VCP 1852:1867 glycosylated VCP 1852:1867 In addition, the LC16m8 virus likely originated from a substrain of VV-Lister that expresses glycosylated VCP. 25030055 7 60 gly glycosylated 1397:1408 arg1 FLAG-VCPg 1415:1423 FLAG-VCPg 1415:1423 FLAG-VCPg 1415:1423 Recombinant vaccinia viruses expressing FLAG-tagged glycosylated VCP (FLAG-VCPg) and nonglycosylated VCP (FLAG-VCP) were constructed based on the Western Reserve strain. 25030055 7 60 gly glycosylated 1397:1408 arg1 VCP 1410:1412 FLAG-tagged glycosylated VCP 1385:1412 FLAG-tagged glycosylated VCP (FLAG-VCPg) 1385:1424 Recombinant vaccinia viruses expressing FLAG-tagged glycosylated VCP (FLAG-VCPg) and nonglycosylated VCP (FLAG-VCP) were constructed based on the Western Reserve strain. 25030055 2 61 theme sequence 488:495 arg1 data 497:500 published sequence data 478:500 published sequence data at that time 478:513 Previously, we reported that an attenuated smallpox vaccine, LC16m8, which was derived from the Lister strain of vaccinia virus (VV-Lister), expressed a glycosylated form of VCP, whereas published sequence data at that time indicated that the VV-Lister VCP has no motif for N-linked glycosylation. 25030055 1 62 theme virus 113:117 arg1 VCP 147:149 VCP 147:149 VCP 147:149 The vaccinia virus complement control protein (VCP) is a secreted viral protein that binds the C3b and C4b complement components and inhibits the classic and alternative complement pathways. 25030055 1 62 theme virus 113:117 arg1 protein 138:144 The vaccinia virus complement control protein 100:144 The vaccinia virus complement control protein (VCP) 100:150 The vaccinia virus complement control protein (VCP) is a secreted viral protein that binds the C3b and C4b complement components and inhibits the classic and alternative complement pathways. 25030055 1 62 theme virus 113:117 arg1 protein 172:178 a secreted viral protein 155:178 a secreted viral protein that binds the C3b and C4b complement components and inhibits the classic and alternative complement pathways 155:288 The vaccinia virus complement control protein (VCP) is a secreted viral protein that binds the C3b and C4b complement components and inhibits the classic and alternative complement pathways. 25030055 7 63 theme FLAG-tagged 1385:1395 arg1 FLAG-VCPg 1415:1423 FLAG-VCPg 1415:1423 FLAG-VCPg 1415:1423 Recombinant vaccinia viruses expressing FLAG-tagged glycosylated VCP (FLAG-VCPg) and nonglycosylated VCP (FLAG-VCP) were constructed based on the Western Reserve strain. 25030055 7 63 theme FLAG-tagged 1385:1395 arg1 VCP 1410:1412 FLAG-tagged glycosylated VCP 1385:1412 FLAG-tagged glycosylated VCP (FLAG-VCPg) 1385:1424 Recombinant vaccinia viruses expressing FLAG-tagged glycosylated VCP (FLAG-VCPg) and nonglycosylated VCP (FLAG-VCP) were constructed based on the Western Reserve strain. 25030055 4 64 gly nonglycosylated 907:921 arg1 VCP 923:925 nonglycosylated VCP 907:925 nonglycosylated VCP 907:925 Expression analysis indicated that VV-Lister contains substrains expressing glycosylated VCP and substrains expressing nonglycosylated VCP. 25030055 9 65 theme LC16m8 1751:1756 arg1 attenuation 1736:1746 the attenuation 1732:1746 the attenuation of LC16m8 1732:1756 Our data suggest that glycosylation did not affect the biological activity of VCP and thus may not have contributed to the attenuation of LC16m8. 25030055 2 66 contain has 548:550 arg1 VCP 544:546 the VV-Lister VCP 530:546 the VV-Lister VCP 530:546 Previously, we reported that an attenuated smallpox vaccine, LC16m8, which was derived from the Lister strain of vaccinia virus (VV-Lister), expressed a glycosylated form of VCP, whereas published sequence data at that time indicated that the VV-Lister VCP has no motif for N-linked glycosylation. 25030055 2 66 contain has 548:550 arg2 motif 555:559 no motif 552:559 no motif for N-linked glycosylation 552:586 Previously, we reported that an attenuated smallpox vaccine, LC16m8, which was derived from the Lister strain of vaccinia virus (VV-Lister), expressed a glycosylated form of VCP, whereas published sequence data at that time indicated that the VV-Lister VCP has no motif for N-linked glycosylation. 25030055 0 67 theme strain 74:79 arg1 protein 52:58 control protein 44:58 control protein of the lister strain of vaccinia virus 44:97 Glycosylated and nonglycosylated complement control protein of the lister strain of vaccinia virus. 25030055 10 68 theme VV-Lister 1827:1835 arg1 substrain 1814:1822 a substrain 1812:1822 a substrain of VV-Lister that expresses glycosylated VCP 1812:1867 In addition, the LC16m8 virus likely originated from a substrain of VV-Lister that expresses glycosylated VCP. 25030055 9 69 theme VCP 1691:1693 arg1 activity 1679:1686 the biological activity 1664:1686 the biological activity of VCP 1664:1693 Our data suggest that glycosylation did not affect the biological activity of VCP and thus may not have contributed to the attenuation of LC16m8. 25030055 7 70 theme Recombinant 1345:1355 arg1 viruses 1366:1372 Recombinant vaccinia viruses 1345:1372 Recombinant vaccinia viruses expressing FLAG-tagged glycosylated VCP (FLAG-VCPg) and nonglycosylated VCP (FLAG-VCP) 1345:1459 Recombinant vaccinia viruses expressing FLAG-tagged glycosylated VCP (FLAG-VCPg) and nonglycosylated VCP (FLAG-VCP) were constructed based on the Western Reserve strain. 25030055 0 71 theme vaccinia 84:91 arg1 virus 93:97 vaccinia virus 84:97 vaccinia virus 84:97 Glycosylated and nonglycosylated complement control protein of the lister strain of vaccinia virus. 25030055 6 72 from isolates 1199:1206 arg1 VCP 1186:1188 partially purified VCP 1167:1188 partially purified VCP from the isolates 1167:1206 Individual Lister virus clones expressing either the glycosylated VCP or the nonglycosylated species were isolated, and partially purified VCP from the isolates were found to be functional equivalents in binding human C3b and C4b complement proteins and inhibiting hemolysis and in immunogenicity. 25030055 3 73 theme VCP 783:785 arg1 origin 756:761 the likely origin 745:761 the likely origin of the glycosylated VCP 745:785 We were interested in determining whether the glycosylation of VCP impairs its biological activity, possibly contributing to the attenuation of LC16m8, and the likely origin of the glycosylated VCP. 25030055 3 73 theme VCP 783:785 arg1 attenuation 718:728 the attenuation 714:728 the attenuation of LC16m8 714:738 We were interested in determining whether the glycosylation of VCP impairs its biological activity, possibly contributing to the attenuation of LC16m8, and the likely origin of the glycosylated VCP. 25030055 5 74 theme smallpox 945:952 arg1 vaccine 954:960 smallpox vaccine 945:960 smallpox vaccine 945:960 Other strains of smallpox vaccine, as well as laboratory strains of vaccinia virus, all expressed nonglycosylated VCP. 25030055 6 75 theme virus 1065:1069 arg1 clones 1071:1076 Individual Lister virus clones 1047:1076 Individual Lister virus clones expressing either the glycosylated VCP or the nonglycosylated species 1047:1146 Individual Lister virus clones expressing either the glycosylated VCP or the nonglycosylated species were isolated, and partially purified VCP from the isolates were found to be functional equivalents in binding human C3b and C4b complement proteins and inhibiting hemolysis and in immunogenicity. 25030055 2 76 theme VCP 465:467 arg1 form 457:460 a glycosylated form 442:460 a glycosylated form of VCP 442:467 Previously, we reported that an attenuated smallpox vaccine, LC16m8, which was derived from the Lister strain of vaccinia virus (VV-Lister), expressed a glycosylated form of VCP, whereas published sequence data at that time indicated that the VV-Lister VCP has no motif for N-linked glycosylation. 25030055 8 77 theme human 1552:1556 arg1 C3b 1558:1560 human C3b 1552:1560 human C3b 1552:1560 Purified FLAG-VCP and FLAG-VCPg bind human C3b and C4b and blocked complement-mediated hemolysis. 25030055 6 78 theme Individual 1047:1056 arg1 clones 1071:1076 Individual Lister virus clones 1047:1076 Individual Lister virus clones expressing either the glycosylated VCP or the nonglycosylated species 1047:1146 Individual Lister virus clones expressing either the glycosylated VCP or the nonglycosylated species were isolated, and partially purified VCP from the isolates were found to be functional equivalents in binding human C3b and C4b complement proteins and inhibiting hemolysis and in immunogenicity. 25030055 2 79 theme virus 413:417 arg1 strain 394:399 the Lister strain 383:399 the Lister strain of vaccinia virus (VV-Lister) 383:429 Previously, we reported that an attenuated smallpox vaccine, LC16m8, which was derived from the Lister strain of vaccinia virus (VV-Lister), expressed a glycosylated form of VCP, whereas published sequence data at that time indicated that the VV-Lister VCP has no motif for N-linked glycosylation. 25030055 1 80 theme alternative 258:268 arg1 pathways 281:288 the classic and alternative complement pathways 242:288 the classic and alternative complement pathways 242:288 The vaccinia virus complement control protein (VCP) is a secreted viral protein that binds the C3b and C4b complement components and inhibits the classic and alternative complement pathways. 25030055 2 81 theme Lister 387:392 arg1 strain 394:399 the Lister strain 383:399 the Lister strain of vaccinia virus (VV-Lister) 383:429 Previously, we reported that an attenuated smallpox vaccine, LC16m8, which was derived from the Lister strain of vaccinia virus (VV-Lister), expressed a glycosylated form of VCP, whereas published sequence data at that time indicated that the VV-Lister VCP has no motif for N-linked glycosylation. 25030055 8 82 theme complement-mediated 1582:1600 arg1 hemolysis 1602:1610 complement-mediated hemolysis 1582:1610 complement-mediated hemolysis 1582:1610 Purified FLAG-VCP and FLAG-VCPg bind human C3b and C4b and blocked complement-mediated hemolysis. 25030055 5 83 theme virus 1005:1009 arg1 strains 934:940 Other strains 928:940 Other strains of smallpox vaccine 928:960 Other strains of smallpox vaccine, as well as laboratory strains of vaccinia virus, all expressed nonglycosylated VCP. 25030055 5 83 theme virus 1005:1009 arg1 strains 985:991 laboratory strains 974:991 laboratory strains of vaccinia virus 974:1009 Other strains of smallpox vaccine, as well as laboratory strains of vaccinia virus, all expressed nonglycosylated VCP. 25030055 4 84 theme nonglycosylated 907:921 arg1 VCP 923:925 nonglycosylated VCP 907:925 nonglycosylated VCP 907:925 Expression analysis indicated that VV-Lister contains substrains expressing glycosylated VCP and substrains expressing nonglycosylated VCP. 25030055 2 85 attach derived 370:376 arg2 LC16m8 352:357 LC16m8 352:357 LC16m8 352:357 Previously, we reported that an attenuated smallpox vaccine, LC16m8, which was derived from the Lister strain of vaccinia virus (VV-Lister), expressed a glycosylated form of VCP, whereas published sequence data at that time indicated that the VV-Lister VCP has no motif for N-linked glycosylation. 25030055 2 85 attach derived 370:376 arg2 vaccine 343:349 an attenuated smallpox vaccine 320:349 an attenuated smallpox vaccine 320:349 Previously, we reported that an attenuated smallpox vaccine, LC16m8, which was derived from the Lister strain of vaccinia virus (VV-Lister), expressed a glycosylated form of VCP, whereas published sequence data at that time indicated that the VV-Lister VCP has no motif for N-linked glycosylation. 25030055 2 85 attach derived 370:376 arg1 strain 394:399 the Lister strain 383:399 the Lister strain of vaccinia virus (VV-Lister) 383:429 Previously, we reported that an attenuated smallpox vaccine, LC16m8, which was derived from the Lister strain of vaccinia virus (VV-Lister), expressed a glycosylated form of VCP, whereas published sequence data at that time indicated that the VV-Lister VCP has no motif for N-linked glycosylation. 25030055 1 86 theme C4b 203:205 arg1 components 218:227 the C3b and C4b complement components 191:227 the C3b and C4b complement components 191:227 The vaccinia virus complement control protein (VCP) is a secreted viral protein that binds the C3b and C4b complement components and inhibits the classic and alternative complement pathways. 25030055 5 87 theme laboratory 974:983 arg1 strains 985:991 laboratory strains 974:991 laboratory strains of vaccinia virus 974:1009 Other strains of smallpox vaccine, as well as laboratory strains of vaccinia virus, all expressed nonglycosylated VCP. 25030055 3 88 theme VCP 652:654 arg1 glycosylation 635:647 the glycosylation 631:647 the glycosylation of VCP 631:654 We were interested in determining whether the glycosylation of VCP impairs its biological activity, possibly contributing to the attenuation of LC16m8, and the likely origin of the glycosylated VCP. 24962585 6 0 theme peptides 982:989 arg1 quantification 932:945 quantification 932:945 quantification 932:945 To characterize the NGT-catalyzed reaction, we developed a sensitive and quantitative in vitro assay based on HPLC separation and quantification of fluorescently labeled substrate peptides. 24962585 6 0 theme peptides 982:989 arg1 separation 917:926 HPLC separation 912:926 HPLC separation 912:926 To characterize the NGT-catalyzed reaction, we developed a sensitive and quantitative in vitro assay based on HPLC separation and quantification of fluorescently labeled substrate peptides. 24962585 7 1 theme substrates 1196:1205 arg1 number 1164:1169 a number 1162:1169 a number of different sugar donor substrates 1162:1205 With this assay we were able to directly quantify glycopeptide formation by Actinobacillus pleuropneumoniae NGT and determine its substrate specificities: NGT turns over a number of different sugar donor substrates and allows for activation by both UDP and GDP. 24962585 7 2 theme glycopeptide 1042:1053 arg1 formation 1055:1063 glycopeptide formation 1042:1063 glycopeptide formation by Actinobacillus pleuropneumoniae NGT 1042:1102 With this assay we were able to directly quantify glycopeptide formation by Actinobacillus pleuropneumoniae NGT and determine its substrate specificities: NGT turns over a number of different sugar donor substrates and allows for activation by both UDP and GDP. 24962585 2 3 from residue 312:318 arg1 S/T 337:339 S/T 337:339 S/T 337:339 The classical, highly conserved pathway entails the assembly of a lipid-linked oligosaccharide and its transfer to an asparagine residue in the sequon NX(S/T) of a secreted protein by the integral membrane protein oligosaccharyltransferase. 24962585 2 3 from residue 312:318 arg1 NX 334:335 the sequon NX 323:335 the sequon NX(S/T) of a secreted protein 323:362 The classical, highly conserved pathway entails the assembly of a lipid-linked oligosaccharide and its transfer to an asparagine residue in the sequon NX(S/T) of a secreted protein by the integral membrane protein oligosaccharyltransferase. 24962585 8 4 theme NX 1428:1429 arg1 substrates 1466:1475 the optimal NGT substrates 1450:1475 the optimal NGT substrates 1450:1475 Quantitative analysis of peptide substrate turnover demonstrated a strikingly similar specificity as the classical, oligosaccharyltransferase-catalyzed N-glycosylation, with NX(S/T) sequons being the optimal NGT substrates. 24962585 8 4 theme NX 1428:1429 arg1 sequons 1436:1442 NX(S/T) sequons 1428:1442 NX(S/T) sequons 1428:1442 Quantitative analysis of peptide substrate turnover demonstrated a strikingly similar specificity as the classical, oligosaccharyltransferase-catalyzed N-glycosylation, with NX(S/T) sequons being the optimal NGT substrates. 24962585 6 5 theme substrate 972:980 arg1 peptides 982:989 fluorescently labeled substrate peptides 950:989 fluorescently labeled substrate peptides 950:989 To characterize the NGT-catalyzed reaction, we developed a sensitive and quantitative in vitro assay based on HPLC separation and quantification of fluorescently labeled substrate peptides. 24962585 8 6 theme turnover 1297:1304 arg1 analysis 1267:1274 Quantitative analysis 1254:1274 Quantitative analysis of peptide substrate turnover 1254:1304 Quantitative analysis of peptide substrate turnover demonstrated a strikingly similar specificity as the classical, oligosaccharyltransferase-catalyzed N-glycosylation, with NX(S/T) sequons being the optimal NGT substrates. 24962585 1 7 theme life 177:180 arg1 kingdoms 165:172 all kingdoms 161:172 all kingdoms of life 161:180 N-Linked protein glycosylation is a very common post-translational modification that can be found in all kingdoms of life. 24962585 2 8 link lipid-linked 249:260 arg1 oligosaccharide 262:276 a lipid-linked oligosaccharide 247:276 a lipid-linked oligosaccharide 247:276 The classical, highly conserved pathway entails the assembly of a lipid-linked oligosaccharide and its transfer to an asparagine residue in the sequon NX(S/T) of a secreted protein by the integral membrane protein oligosaccharyltransferase. 24962585 1 9 located found 152:156 arg1 kingdoms 165:172 all kingdoms 161:172 all kingdoms of life 161:180 N-Linked protein glycosylation is a very common post-translational modification that can be found in all kingdoms of life. 24962585 1 9 located found 152:156 arg2 modification 127:138 a very common post-translational modification 94:138 a very common post-translational modification that can be found in all kingdoms of life 94:180 N-Linked protein glycosylation is a very common post-translational modification that can be found in all kingdoms of life. 24962585 1 9 located found 152:156 arg2 glycosylation 77:89 N-Linked protein glycosylation 60:89 N-Linked protein glycosylation 60:89 N-Linked protein glycosylation is a very common post-translational modification that can be found in all kingdoms of life. 24962585 7 10 theme sugar 1184:1188 arg1 substrates 1196:1205 different sugar donor substrates 1174:1205 different sugar donor substrates 1174:1205 With this assay we were able to directly quantify glycopeptide formation by Actinobacillus pleuropneumoniae NGT and determine its substrate specificities: NGT turns over a number of different sugar donor substrates and allows for activation by both UDP and GDP. 24962585 6 11 theme sensitive 861:869 arg1 assay 897:901 a sensitive and quantitative in vitro assay 859:901 a sensitive and quantitative in vitro assay based on HPLC separation and quantification of fluorescently labeled substrate peptides 859:989 To characterize the NGT-catalyzed reaction, we developed a sensitive and quantitative in vitro assay based on HPLC separation and quantification of fluorescently labeled substrate peptides. 24962585 2 12 theme asparagine 301:310 arg1 residue 312:318 an asparagine residue 298:318 an asparagine residue in the sequon NX(S/T) of a secreted protein 298:362 The classical, highly conserved pathway entails the assembly of a lipid-linked oligosaccharide and its transfer to an asparagine residue in the sequon NX(S/T) of a secreted protein by the integral membrane protein oligosaccharyltransferase. 24962585 1 13 theme common 101:106 arg1 glycosylation 77:89 N-Linked protein glycosylation 60:89 N-Linked protein glycosylation 60:89 N-Linked protein glycosylation is a very common post-translational modification that can be found in all kingdoms of life. 24962585 1 13 theme common 101:106 arg1 modification 127:138 a very common post-translational modification 94:138 a very common post-translational modification that can be found in all kingdoms of life 94:180 N-Linked protein glycosylation is a very common post-translational modification that can be found in all kingdoms of life. 24962585 7 14 theme donor 1190:1194 arg1 substrates 1196:1205 different sugar donor substrates 1174:1205 different sugar donor substrates 1174:1205 With this assay we were able to directly quantify glycopeptide formation by Actinobacillus pleuropneumoniae NGT and determine its substrate specificities: NGT turns over a number of different sugar donor substrates and allows for activation by both UDP and GDP. 24962585 8 15 dep classical 1359:1367 arg1 oligosaccharyltransferase-catalyzed 1370:1404 oligosaccharyltransferase-catalyzed 1370:1404 oligosaccharyltransferase-catalyzed 1370:1404 Quantitative analysis of peptide substrate turnover demonstrated a strikingly similar specificity as the classical, oligosaccharyltransferase-catalyzed N-glycosylation, with NX(S/T) sequons being the optimal NGT substrates. 24962585 2 16 dep classical 187:195 arg1 conserved 205:213 conserved 205:213 conserved 205:213 The classical, highly conserved pathway entails the assembly of a lipid-linked oligosaccharide and its transfer to an asparagine residue in the sequon NX(S/T) of a secreted protein by the integral membrane protein oligosaccharyltransferase. 24962585 5 17 theme catalyzing 782:791 arg1 enzymes 793:799 N-glycosylation catalyzing enzymes 766:799 N-glycosylation catalyzing enzymes 766:799 As these enzymes are not related to oligosaccharyltransferase, NGTs constitute a novel class of N-glycosylation catalyzing enzymes. 24962585 8 18 theme optimal 1454:1460 arg1 substrates 1466:1475 the optimal NGT substrates 1450:1475 the optimal NGT substrates 1450:1475 Quantitative analysis of peptide substrate turnover demonstrated a strikingly similar specificity as the classical, oligosaccharyltransferase-catalyzed N-glycosylation, with NX(S/T) sequons being the optimal NGT substrates. 24962585 8 18 theme optimal 1454:1460 arg1 sequons 1436:1442 NX(S/T) sequons 1428:1442 NX(S/T) sequons 1428:1442 Quantitative analysis of peptide substrate turnover demonstrated a strikingly similar specificity as the classical, oligosaccharyltransferase-catalyzed N-glycosylation, with NX(S/T) sequons being the optimal NGT substrates. 24962585 2 19 theme membrane 380:387 arg1 protein 389:395 the integral membrane protein 367:395 the integral membrane protein oligosaccharyltransferase 367:421 The classical, highly conserved pathway entails the assembly of a lipid-linked oligosaccharide and its transfer to an asparagine residue in the sequon NX(S/T) of a secreted protein by the integral membrane protein oligosaccharyltransferase. 24962585 5 20 theme enzymes 793:799 arg1 class 757:761 a novel class 749:761 a novel class of N-glycosylation catalyzing enzymes 749:799 As these enzymes are not related to oligosaccharyltransferase, NGTs constitute a novel class of N-glycosylation catalyzing enzymes. 24962585 7 21 theme different 1174:1182 arg1 substrates 1196:1205 different sugar donor substrates 1174:1205 different sugar donor substrates 1174:1205 With this assay we were able to directly quantify glycopeptide formation by Actinobacillus pleuropneumoniae NGT and determine its substrate specificities: NGT turns over a number of different sugar donor substrates and allows for activation by both UDP and GDP. 24962585 2 22 theme integral 371:378 arg1 protein 389:395 the integral membrane protein 367:395 the integral membrane protein oligosaccharyltransferase 367:421 The classical, highly conserved pathway entails the assembly of a lipid-linked oligosaccharide and its transfer to an asparagine residue in the sequon NX(S/T) of a secreted protein by the integral membrane protein oligosaccharyltransferase. 24962585 8 23 theme Quantitative 1254:1265 arg1 analysis 1267:1274 Quantitative analysis 1254:1274 Quantitative analysis of peptide substrate turnover 1254:1304 Quantitative analysis of peptide substrate turnover demonstrated a strikingly similar specificity as the classical, oligosaccharyltransferase-catalyzed N-glycosylation, with NX(S/T) sequons being the optimal NGT substrates. 24962585 3 24 theme soluble 529:535 arg1 NGT 560:562 NGT 560:562 NGT 560:562 A few species in the class of γ-proteobacteria encode a cytoplasmic N-glycosylation system mediated by a soluble N-glycosyltransferase (NGT). 24962585 3 24 theme soluble 529:535 arg1 N-glycosyltransferase 537:557 a soluble N-glycosyltransferase 527:557 a soluble N-glycosyltransferase (NGT) 527:563 A few species in the class of γ-proteobacteria encode a cytoplasmic N-glycosylation system mediated by a soluble N-glycosyltransferase (NGT). 24962585 2 25 theme sequon 327:332 arg1 S/T 337:339 S/T 337:339 S/T 337:339 The classical, highly conserved pathway entails the assembly of a lipid-linked oligosaccharide and its transfer to an asparagine residue in the sequon NX(S/T) of a secreted protein by the integral membrane protein oligosaccharyltransferase. 24962585 2 25 theme sequon 327:332 arg1 NX 334:335 the sequon NX 323:335 the sequon NX(S/T) of a secreted protein 323:362 The classical, highly conserved pathway entails the assembly of a lipid-linked oligosaccharide and its transfer to an asparagine residue in the sequon NX(S/T) of a secreted protein by the integral membrane protein oligosaccharyltransferase. 24962585 3 26 theme few 426:428 arg1 system 508:513 a cytoplasmic N-glycosylation system 478:513 a cytoplasmic N-glycosylation system mediated by a soluble N-glycosyltransferase (NGT) 478:563 A few species in the class of γ-proteobacteria encode a cytoplasmic N-glycosylation system mediated by a soluble N-glycosyltransferase (NGT). 24962585 3 26 theme few 426:428 arg1 species 430:436 A few species 424:436 A few species in the class of γ-proteobacteria 424:469 A few species in the class of γ-proteobacteria encode a cytoplasmic N-glycosylation system mediated by a soluble N-glycosyltransferase (NGT). 24962585 0 27 theme Substrate 0:8 arg1 specificity 10:20 Substrate specificity 0:20 Substrate specificity of cytoplasmic N-glycosyltransferase 0:57 Substrate specificity of cytoplasmic N-glycosyltransferase. 24962585 6 28 dep in 888:889 arg1 vitro 891:895 vitro 891:895 vitro 891:895 To characterize the NGT-catalyzed reaction, we developed a sensitive and quantitative in vitro assay based on HPLC separation and quantification of fluorescently labeled substrate peptides. 24962585 7 29 theme NGT 1147:1149 arg1 turns 1151:1155 NGT turns 1147:1155 its substrate specificities: NGT turns over a number of different sugar donor substrates 1118:1205 With this assay we were able to directly quantify glycopeptide formation by Actinobacillus pleuropneumoniae NGT and determine its substrate specificities: NGT turns over a number of different sugar donor substrates and allows for activation by both UDP and GDP. 24962585 1 30 theme post-translational 108:125 arg1 glycosylation 77:89 N-Linked protein glycosylation 60:89 N-Linked protein glycosylation 60:89 N-Linked protein glycosylation is a very common post-translational modification that can be found in all kingdoms of life. 24962585 1 30 theme post-translational 108:125 arg1 modification 127:138 a very common post-translational modification 94:138 a very common post-translational modification that can be found in all kingdoms of life 94:180 N-Linked protein glycosylation is a very common post-translational modification that can be found in all kingdoms of life. 24962585 8 31 theme peptide 1279:1285 arg1 turnover 1297:1304 peptide substrate turnover 1279:1304 peptide substrate turnover 1279:1304 Quantitative analysis of peptide substrate turnover demonstrated a strikingly similar specificity as the classical, oligosaccharyltransferase-catalyzed N-glycosylation, with NX(S/T) sequons being the optimal NGT substrates. 24962585 6 32 theme HPLC 912:915 arg1 separation 917:926 HPLC separation 912:926 HPLC separation 912:926 To characterize the NGT-catalyzed reaction, we developed a sensitive and quantitative in vitro assay based on HPLC separation and quantification of fluorescently labeled substrate peptides. 24962585 0 33 theme cytoplasmic 25:35 arg1 N-glycosyltransferase 37:57 cytoplasmic N-glycosyltransferase 25:57 cytoplasmic N-glycosyltransferase 25:57 Substrate specificity of cytoplasmic N-glycosyltransferase. 24962585 2 34 theme oligosaccharide 262:276 arg1 transfer 286:293 its transfer 282:293 its transfer to an asparagine residue in the sequon NX(S/T) of a secreted protein 282:362 The classical, highly conserved pathway entails the assembly of a lipid-linked oligosaccharide and its transfer to an asparagine residue in the sequon NX(S/T) of a secreted protein by the integral membrane protein oligosaccharyltransferase. 24962585 2 34 theme oligosaccharide 262:276 arg1 assembly 235:242 the assembly 231:242 the assembly of a lipid-linked oligosaccharide 231:276 The classical, highly conserved pathway entails the assembly of a lipid-linked oligosaccharide and its transfer to an asparagine residue in the sequon NX(S/T) of a secreted protein by the integral membrane protein oligosaccharyltransferase. 24962585 6 35 theme NGT-catalyzed 822:834 arg1 reaction 836:843 the NGT-catalyzed reaction 818:843 the NGT-catalyzed reaction 818:843 To characterize the NGT-catalyzed reaction, we developed a sensitive and quantitative in vitro assay based on HPLC separation and quantification of fluorescently labeled substrate peptides. 24962585 3 36 theme γ-proteobacteria 454:469 arg1 class 445:449 the class 441:449 the class of γ-proteobacteria 441:469 A few species in the class of γ-proteobacteria encode a cytoplasmic N-glycosylation system mediated by a soluble N-glycosyltransferase (NGT). 24962585 8 37 theme NGT 1462:1464 arg1 substrates 1466:1475 the optimal NGT substrates 1450:1475 the optimal NGT substrates 1450:1475 Quantitative analysis of peptide substrate turnover demonstrated a strikingly similar specificity as the classical, oligosaccharyltransferase-catalyzed N-glycosylation, with NX(S/T) sequons being the optimal NGT substrates. 24962585 8 37 theme NGT 1462:1464 arg1 sequons 1436:1442 NX(S/T) sequons 1428:1442 NX(S/T) sequons 1428:1442 Quantitative analysis of peptide substrate turnover demonstrated a strikingly similar specificity as the classical, oligosaccharyltransferase-catalyzed N-glycosylation, with NX(S/T) sequons being the optimal NGT substrates. 24962585 7 38 gly glycopeptide 1042:1053 arg2 glycopeptide 1042:1053 glycopeptide formation 1042:1063 glycopeptide formation by Actinobacillus pleuropneumoniae NGT 1042:1102 With this assay we were able to directly quantify glycopeptide formation by Actinobacillus pleuropneumoniae NGT and determine its substrate specificities: NGT turns over a number of different sugar donor substrates and allows for activation by both UDP and GDP. 24962585 8 39 theme substrate 1287:1295 arg1 turnover 1297:1304 peptide substrate turnover 1279:1304 peptide substrate turnover 1279:1304 Quantitative analysis of peptide substrate turnover demonstrated a strikingly similar specificity as the classical, oligosaccharyltransferase-catalyzed N-glycosylation, with NX(S/T) sequons being the optimal NGT substrates. 24962585 5 40 theme novel 751:755 arg1 class 757:761 a novel class 749:761 a novel class of N-glycosylation catalyzing enzymes 749:799 As these enzymes are not related to oligosaccharyltransferase, NGTs constitute a novel class of N-glycosylation catalyzing enzymes. 24962585 2 41 theme classical 187:195 arg1 pathway 215:221 The classical, highly conserved pathway 183:221 The classical, highly conserved pathway 183:221 The classical, highly conserved pathway entails the assembly of a lipid-linked oligosaccharide and its transfer to an asparagine residue in the sequon NX(S/T) of a secreted protein by the integral membrane protein oligosaccharyltransferase. 24962585 8 42 theme similar 1332:1338 arg1 specificity 1340:1350 a strikingly similar specificity 1319:1350 a strikingly similar specificity as the classical, oligosaccharyltransferase-catalyzed N-glycosylation 1319:1420 Quantitative analysis of peptide substrate turnover demonstrated a strikingly similar specificity as the classical, oligosaccharyltransferase-catalyzed N-glycosylation, with NX(S/T) sequons being the optimal NGT substrates. 24962585 0 43 theme N-glycosyltransferase 37:57 arg1 specificity 10:20 Substrate specificity 0:20 Substrate specificity of cytoplasmic N-glycosyltransferase 0:57 Substrate specificity of cytoplasmic N-glycosyltransferase. 24962585 4 44 theme nucleotide-activated 583:602 arg1 sugars 604:609 nucleotide-activated sugars 583:609 nucleotide-activated sugars 583:609 This enzyme uses nucleotide-activated sugars to modify asparagine residues with single monosaccharides. 24962585 2 45 theme protein 389:395 arg1 oligosaccharyltransferase 397:421 the integral membrane protein oligosaccharyltransferase 367:421 the integral membrane protein oligosaccharyltransferase 367:421 The classical, highly conserved pathway entails the assembly of a lipid-linked oligosaccharide and its transfer to an asparagine residue in the sequon NX(S/T) of a secreted protein by the integral membrane protein oligosaccharyltransferase. 24962585 7 46 with able 1016:1019 arg1 assay 1002:1006 this assay 997:1006 this assay 997:1006 With this assay we were able to directly quantify glycopeptide formation by Actinobacillus pleuropneumoniae NGT and determine its substrate specificities: NGT turns over a number of different sugar donor substrates and allows for activation by both UDP and GDP. 24962585 7 47 theme substrate 1122:1130 arg1 specificities 1132:1144 its substrate specificities 1118:1144 its substrate specificities: NGT turns over a number of different sugar donor substrates 1118:1205 With this assay we were able to directly quantify glycopeptide formation by Actinobacillus pleuropneumoniae NGT and determine its substrate specificities: NGT turns over a number of different sugar donor substrates and allows for activation by both UDP and GDP. 24962585 4 48 with residues 632:639 arg1 monosaccharides 653:667 single monosaccharides 646:667 single monosaccharides 646:667 This enzyme uses nucleotide-activated sugars to modify asparagine residues with single monosaccharides. 24962585 3 49 theme N-glycosylation 492:506 arg1 system 508:513 a cytoplasmic N-glycosylation system 478:513 a cytoplasmic N-glycosylation system mediated by a soluble N-glycosyltransferase (NGT) 478:563 A few species in the class of γ-proteobacteria encode a cytoplasmic N-glycosylation system mediated by a soluble N-glycosyltransferase (NGT). 24962585 3 49 theme N-glycosylation 492:506 arg1 species 430:436 A few species 424:436 A few species in the class of γ-proteobacteria 424:469 A few species in the class of γ-proteobacteria encode a cytoplasmic N-glycosylation system mediated by a soluble N-glycosyltransferase (NGT). 24962585 6 50 theme labeled 964:970 arg1 peptides 982:989 fluorescently labeled substrate peptides 950:989 fluorescently labeled substrate peptides 950:989 To characterize the NGT-catalyzed reaction, we developed a sensitive and quantitative in vitro assay based on HPLC separation and quantification of fluorescently labeled substrate peptides. 24962585 7 51 theme Actinobacillus 1068:1081 arg1 NGT 1100:1102 Actinobacillus pleuropneumoniae NGT 1068:1102 Actinobacillus pleuropneumoniae NGT 1068:1102 With this assay we were able to directly quantify glycopeptide formation by Actinobacillus pleuropneumoniae NGT and determine its substrate specificities: NGT turns over a number of different sugar donor substrates and allows for activation by both UDP and GDP. 24962585 1 52 theme protein 69:75 arg1 glycosylation 77:89 N-Linked protein glycosylation 60:89 N-Linked protein glycosylation 60:89 N-Linked protein glycosylation is a very common post-translational modification that can be found in all kingdoms of life. 24962585 1 52 theme protein 69:75 arg1 modification 127:138 a very common post-translational modification 94:138 a very common post-translational modification that can be found in all kingdoms of life 94:180 N-Linked protein glycosylation is a very common post-translational modification that can be found in all kingdoms of life. 24962585 7 53 theme pleuropneumoniae 1083:1098 arg1 NGT 1100:1102 Actinobacillus pleuropneumoniae NGT 1068:1102 Actinobacillus pleuropneumoniae NGT 1068:1102 With this assay we were able to directly quantify glycopeptide formation by Actinobacillus pleuropneumoniae NGT and determine its substrate specificities: NGT turns over a number of different sugar donor substrates and allows for activation by both UDP and GDP. 24962585 7 54 dep able 1016:1019 arg1 determine 1108:1116 determine 1108:1116 determine its substrate specificities: NGT turns over a number of different sugar donor substrates 1108:1205 With this assay we were able to directly quantify glycopeptide formation by Actinobacillus pleuropneumoniae NGT and determine its substrate specificities: NGT turns over a number of different sugar donor substrates and allows for activation by both UDP and GDP. 24962585 7 54 dep able 1016:1019 arg1 quantify 1033:1040 quantify 1033:1040 quantify glycopeptide formation by Actinobacillus pleuropneumoniae NGT 1033:1102 With this assay we were able to directly quantify glycopeptide formation by Actinobacillus pleuropneumoniae NGT and determine its substrate specificities: NGT turns over a number of different sugar donor substrates and allows for activation by both UDP and GDP. 24962585 7 54 dep able 1016:1019 arg1 allows 1211:1216 allows 1211:1216 allows for activation by both UDP and GDP 1211:1251 With this assay we were able to directly quantify glycopeptide formation by Actinobacillus pleuropneumoniae NGT and determine its substrate specificities: NGT turns over a number of different sugar donor substrates and allows for activation by both UDP and GDP. 24962585 8 55 theme classical 1359:1367 arg1 N-glycosylation 1406:1420 the classical, oligosaccharyltransferase-catalyzed N-glycosylation 1355:1420 the classical, oligosaccharyltransferase-catalyzed N-glycosylation 1355:1420 Quantitative analysis of peptide substrate turnover demonstrated a strikingly similar specificity as the classical, oligosaccharyltransferase-catalyzed N-glycosylation, with NX(S/T) sequons being the optimal NGT substrates. 24962585 6 56 theme in 888:889 arg1 assay 897:901 a sensitive and quantitative in vitro assay 859:901 a sensitive and quantitative in vitro assay based on HPLC separation and quantification of fluorescently labeled substrate peptides 859:989 To characterize the NGT-catalyzed reaction, we developed a sensitive and quantitative in vitro assay based on HPLC separation and quantification of fluorescently labeled substrate peptides. 24962585 3 57 theme cytoplasmic 480:490 arg1 system 508:513 a cytoplasmic N-glycosylation system 478:513 a cytoplasmic N-glycosylation system mediated by a soluble N-glycosyltransferase (NGT) 478:563 A few species in the class of γ-proteobacteria encode a cytoplasmic N-glycosylation system mediated by a soluble N-glycosyltransferase (NGT). 24962585 3 57 theme cytoplasmic 480:490 arg1 species 430:436 A few species 424:436 A few species in the class of γ-proteobacteria 424:469 A few species in the class of γ-proteobacteria encode a cytoplasmic N-glycosylation system mediated by a soluble N-glycosyltransferase (NGT). 24962585 7 58 dep specificities 1132:1144 arg1 turns 1151:1155 NGT turns 1147:1155 its substrate specificities: NGT turns over a number of different sugar donor substrates 1118:1205 With this assay we were able to directly quantify glycopeptide formation by Actinobacillus pleuropneumoniae NGT and determine its substrate specificities: NGT turns over a number of different sugar donor substrates and allows for activation by both UDP and GDP. 24962585 4 59 theme asparagine 621:630 arg1 residues 632:639 asparagine residues 621:639 asparagine residues with single monosaccharides 621:667 This enzyme uses nucleotide-activated sugars to modify asparagine residues with single monosaccharides. 24962585 6 60 theme quantitative 875:886 arg1 assay 897:901 a sensitive and quantitative in vitro assay 859:901 a sensitive and quantitative in vitro assay based on HPLC separation and quantification of fluorescently labeled substrate peptides 859:989 To characterize the NGT-catalyzed reaction, we developed a sensitive and quantitative in vitro assay based on HPLC separation and quantification of fluorescently labeled substrate peptides. 24962585 1 61 theme N-Linked 60:67 arg1 glycosylation 77:89 N-Linked protein glycosylation 60:89 N-Linked protein glycosylation 60:89 N-Linked protein glycosylation is a very common post-translational modification that can be found in all kingdoms of life. 24962585 1 61 theme N-Linked 60:67 arg1 modification 127:138 a very common post-translational modification 94:138 a very common post-translational modification that can be found in all kingdoms of life 94:180 N-Linked protein glycosylation is a very common post-translational modification that can be found in all kingdoms of life. 24962585 3 62 from species 430:436 arg1 class 445:449 the class 441:449 the class of γ-proteobacteria 441:469 A few species in the class of γ-proteobacteria encode a cytoplasmic N-glycosylation system mediated by a soluble N-glycosyltransferase (NGT). 24962585 2 63 theme protein 356:362 arg1 S/T 337:339 S/T 337:339 S/T 337:339 The classical, highly conserved pathway entails the assembly of a lipid-linked oligosaccharide and its transfer to an asparagine residue in the sequon NX(S/T) of a secreted protein by the integral membrane protein oligosaccharyltransferase. 24962585 2 63 theme protein 356:362 arg1 NX 334:335 the sequon NX 323:335 the sequon NX(S/T) of a secreted protein 323:362 The classical, highly conserved pathway entails the assembly of a lipid-linked oligosaccharide and its transfer to an asparagine residue in the sequon NX(S/T) of a secreted protein by the integral membrane protein oligosaccharyltransferase. 24962585 4 64 theme single 646:651 arg1 monosaccharides 653:667 single monosaccharides 646:667 single monosaccharides 646:667 This enzyme uses nucleotide-activated sugars to modify asparagine residues with single monosaccharides. 24962585 2 65 theme lipid-linked 249:260 arg1 oligosaccharide 262:276 a lipid-linked oligosaccharide 247:276 a lipid-linked oligosaccharide 247:276 The classical, highly conserved pathway entails the assembly of a lipid-linked oligosaccharide and its transfer to an asparagine residue in the sequon NX(S/T) of a secreted protein by the integral membrane protein oligosaccharyltransferase. 24962585 2 66 theme secreted 347:354 arg1 protein 356:362 a secreted protein 345:362 a secreted protein 345:362 The classical, highly conserved pathway entails the assembly of a lipid-linked oligosaccharide and its transfer to an asparagine residue in the sequon NX(S/T) of a secreted protein by the integral membrane protein oligosaccharyltransferase. 24962585 5 67 theme N-glycosylation 766:780 arg1 enzymes 793:799 N-glycosylation catalyzing enzymes 766:799 N-glycosylation catalyzing enzymes 766:799 As these enzymes are not related to oligosaccharyltransferase, NGTs constitute a novel class of N-glycosylation catalyzing enzymes. 24561051 2 0 theme AGH 293:295 arg1 cDNAs 297:301 12 new AGH cDNAs 286:301 12 new AGH cDNAs in species belonging to five different families of the infra-order Ligiamorpha of terrestrial isopods 286:403 In this study, we amplified 12 new AGH cDNAs in species belonging to five different families of the infra-order Ligiamorpha of terrestrial isopods. 24561051 6 1 theme feminizing 1154:1163 arg1 bacteria 1179:1186 widespread feminizing endosymbiotic bacteria 1143:1186 widespread feminizing endosymbiotic bacteria in isopods 1143:1197 An in-depth understanding of the regulation of AGH expression would help deciphering the interaction between Wolbachia, widespread feminizing endosymbiotic bacteria in isopods, and the sex differentiation of their hosts. 24561051 6 2 from differentiation 1212:1226 arg1 isopods 1191:1197 isopods 1191:1197 isopods 1191:1197 An in-depth understanding of the regulation of AGH expression would help deciphering the interaction between Wolbachia, widespread feminizing endosymbiotic bacteria in isopods, and the sex differentiation of their hosts. 24561051 0 3 from evolution 10:18 arg1 isopods 61:67 terrestrial isopods 49:67 terrestrial isopods 49:67 Molecular evolution of the androgenic hormone in terrestrial isopods. 24561051 2 4 theme new 289:291 arg1 cDNAs 297:301 12 new AGH cDNAs 286:301 12 new AGH cDNAs in species belonging to five different families of the infra-order Ligiamorpha of terrestrial isopods 286:403 In this study, we amplified 12 new AGH cDNAs in species belonging to five different families of the infra-order Ligiamorpha of terrestrial isopods. 24561051 5 5 theme Armadillidiidae 896:910 arg1 families 935:942 the Armadillidiidae and the Porcellionidae families 892:942 the Armadillidiidae and the Porcellionidae families which are congruent with the narrow specificity of AG heterospecific grafting 892:1020 The phylogenetic relationships of AGH sequences allowed one to distinguish two main clades, corresponding to members of the Armadillidiidae and the Porcellionidae families which are congruent with the narrow specificity of AG heterospecific grafting. 24561051 5 5 theme Armadillidiidae 896:910 arg1 congruent 954:962 congruent 954:962 congruent 954:962 The phylogenetic relationships of AGH sequences allowed one to distinguish two main clades, corresponding to members of the Armadillidiidae and the Porcellionidae families which are congruent with the narrow specificity of AG heterospecific grafting. 24561051 5 6 theme heterospecific 998:1011 arg1 grafting 1013:1020 AG heterospecific grafting 995:1020 AG heterospecific grafting 995:1020 The phylogenetic relationships of AGH sequences allowed one to distinguish two main clades, corresponding to members of the Armadillidiidae and the Porcellionidae families which are congruent with the narrow specificity of AG heterospecific grafting. 24561051 5 7 theme families 935:942 arg1 members 881:887 members 881:887 members of the Armadillidiidae and the Porcellionidae families which are congruent with the narrow specificity of AG heterospecific grafting 881:1020 The phylogenetic relationships of AGH sequences allowed one to distinguish two main clades, corresponding to members of the Armadillidiidae and the Porcellionidae families which are congruent with the narrow specificity of AG heterospecific grafting. 24561051 3 8 link N-linked 610:617 arg1 motif 633:637 a putative N-linked glycosylation motif 599:637 a putative N-linked glycosylation motif on the A chains 599:653 Putative essential amino acids for the production of a functional AGH protein exhibit signatures of negative selection and are strictly conserved including typical proteolytic cleavage motifs, a putative N-linked glycosylation motif on the A chains and the eight Cys positions. 24561051 1 9 theme primary 212:218 arg1 characters 246:255 the primary and secondary male sexual characters 208:255 the primary and secondary male sexual characters 208:255 In crustaceans, the androgenic gland (AG), thanks to the synthesis of the androgenic gland hormone (AGH), controls the differentiation of the primary and secondary male sexual characters. 24561051 4 10 theme insulin-like 687:698 arg1 factor 707:712 insulin-like growth factor 687:712 An insulin-like growth factor motif 684:718 An insulin-like growth factor motif was also identified in Armadillidium AGH sequences. 24561051 3 11 theme A 646:646 arg1 chains 648:653 the A chains 642:653 the A chains 642:653 Putative essential amino acids for the production of a functional AGH protein exhibit signatures of negative selection and are strictly conserved including typical proteolytic cleavage motifs, a putative N-linked glycosylation motif on the A chains and the eight Cys positions. 24561051 6 12 theme expression 1074:1083 arg1 regulation 1056:1065 the regulation 1052:1065 the regulation of AGH expression 1052:1083 An in-depth understanding of the regulation of AGH expression would help deciphering the interaction between Wolbachia, widespread feminizing endosymbiotic bacteria in isopods, and the sex differentiation of their hosts. 24561051 6 13 from bacteria 1179:1186 arg1 isopods 1191:1197 isopods 1191:1197 isopods 1191:1197 An in-depth understanding of the regulation of AGH expression would help deciphering the interaction between Wolbachia, widespread feminizing endosymbiotic bacteria in isopods, and the sex differentiation of their hosts. 24561051 5 14 theme AGH 806:808 arg1 sequences 810:818 AGH sequences 806:818 AGH sequences 806:818 The phylogenetic relationships of AGH sequences allowed one to distinguish two main clades, corresponding to members of the Armadillidiidae and the Porcellionidae families which are congruent with the narrow specificity of AG heterospecific grafting. 24561051 3 15 theme AGH 472:474 arg1 protein 476:482 a functional AGH protein 459:482 a functional AGH protein 459:482 Putative essential amino acids for the production of a functional AGH protein exhibit signatures of negative selection and are strictly conserved including typical proteolytic cleavage motifs, a putative N-linked glycosylation motif on the A chains and the eight Cys positions. 24561051 6 16 theme in-depth 1026:1033 arg1 understanding 1035:1047 An in-depth understanding 1023:1047 An in-depth understanding of the regulation of AGH expression 1023:1083 An in-depth understanding of the regulation of AGH expression would help deciphering the interaction between Wolbachia, widespread feminizing endosymbiotic bacteria in isopods, and the sex differentiation of their hosts. 24561051 3 17 theme protein 476:482 arg1 production 445:454 the production 441:454 the production of a functional AGH protein 441:482 Putative essential amino acids for the production of a functional AGH protein exhibit signatures of negative selection and are strictly conserved including typical proteolytic cleavage motifs, a putative N-linked glycosylation motif on the A chains and the eight Cys positions. 24561051 6 18 theme AGH 1070:1072 arg1 expression 1074:1083 AGH expression 1070:1083 AGH expression 1070:1083 An in-depth understanding of the regulation of AGH expression would help deciphering the interaction between Wolbachia, widespread feminizing endosymbiotic bacteria in isopods, and the sex differentiation of their hosts. 24561051 6 19 theme sex 1208:1210 arg1 differentiation 1212:1226 the sex differentiation 1204:1226 the sex differentiation of their hosts 1204:1241 An in-depth understanding of the regulation of AGH expression would help deciphering the interaction between Wolbachia, widespread feminizing endosymbiotic bacteria in isopods, and the sex differentiation of their hosts. 24561051 2 20 theme terrestrial 385:395 arg1 isopods 397:403 terrestrial isopods 385:403 terrestrial isopods 385:403 In this study, we amplified 12 new AGH cDNAs in species belonging to five different families of the infra-order Ligiamorpha of terrestrial isopods. 24561051 3 21 theme Cys 669:671 arg1 positions 673:681 the eight Cys positions 659:681 the eight Cys positions 659:681 Putative essential amino acids for the production of a functional AGH protein exhibit signatures of negative selection and are strictly conserved including typical proteolytic cleavage motifs, a putative N-linked glycosylation motif on the A chains and the eight Cys positions. 24561051 5 22 theme narrow 973:978 arg1 specificity 980:990 the narrow specificity 969:990 the narrow specificity of AG heterospecific grafting 969:1020 The phylogenetic relationships of AGH sequences allowed one to distinguish two main clades, corresponding to members of the Armadillidiidae and the Porcellionidae families which are congruent with the narrow specificity of AG heterospecific grafting. 24561051 3 23 theme selection 515:523 arg1 signatures 492:501 signatures 492:501 signatures of negative selection 492:523 Putative essential amino acids for the production of a functional AGH protein exhibit signatures of negative selection and are strictly conserved including typical proteolytic cleavage motifs, a putative N-linked glycosylation motif on the A chains and the eight Cys positions. 24561051 3 24 from motifs 591:596 arg1 chains 648:653 the A chains 642:653 the A chains 642:653 Putative essential amino acids for the production of a functional AGH protein exhibit signatures of negative selection and are strictly conserved including typical proteolytic cleavage motifs, a putative N-linked glycosylation motif on the A chains and the eight Cys positions. 24561051 1 25 theme androgenic 144:153 arg1 AGH 170:172 AGH 170:172 AGH 170:172 In crustaceans, the androgenic gland (AG), thanks to the synthesis of the androgenic gland hormone (AGH), controls the differentiation of the primary and secondary male sexual characters. 24561051 1 25 theme androgenic 144:153 arg1 hormone 161:167 the androgenic gland hormone 140:167 the androgenic gland hormone (AGH) 140:173 In crustaceans, the androgenic gland (AG), thanks to the synthesis of the androgenic gland hormone (AGH), controls the differentiation of the primary and secondary male sexual characters. 24561051 0 26 theme Molecular 0:8 arg1 evolution 10:18 Molecular evolution 0:18 Molecular evolution of the androgenic hormone in terrestrial isopods 0:67 Molecular evolution of the androgenic hormone in terrestrial isopods. 24561051 1 27 theme secondary 224:232 arg1 characters 246:255 the primary and secondary male sexual characters 208:255 the primary and secondary male sexual characters 208:255 In crustaceans, the androgenic gland (AG), thanks to the synthesis of the androgenic gland hormone (AGH), controls the differentiation of the primary and secondary male sexual characters. 24561051 6 28 theme widespread 1143:1152 arg1 bacteria 1179:1186 widespread feminizing endosymbiotic bacteria 1143:1186 widespread feminizing endosymbiotic bacteria in isopods 1143:1197 An in-depth understanding of the regulation of AGH expression would help deciphering the interaction between Wolbachia, widespread feminizing endosymbiotic bacteria in isopods, and the sex differentiation of their hosts. 24561051 1 29 theme gland 155:159 arg1 AGH 170:172 AGH 170:172 AGH 170:172 In crustaceans, the androgenic gland (AG), thanks to the synthesis of the androgenic gland hormone (AGH), controls the differentiation of the primary and secondary male sexual characters. 24561051 1 29 theme gland 155:159 arg1 hormone 161:167 the androgenic gland hormone 140:167 the androgenic gland hormone (AGH) 140:173 In crustaceans, the androgenic gland (AG), thanks to the synthesis of the androgenic gland hormone (AGH), controls the differentiation of the primary and secondary male sexual characters. 24561051 2 30 theme Ligiamorpha 370:380 arg1 families 342:349 five different families 327:349 five different families of the infra-order Ligiamorpha of terrestrial isopods 327:403 In this study, we amplified 12 new AGH cDNAs in species belonging to five different families of the infra-order Ligiamorpha of terrestrial isopods. 24561051 1 31 theme male 234:237 arg1 characters 246:255 the primary and secondary male sexual characters 208:255 the primary and secondary male sexual characters 208:255 In crustaceans, the androgenic gland (AG), thanks to the synthesis of the androgenic gland hormone (AGH), controls the differentiation of the primary and secondary male sexual characters. 24561051 2 32 from cDNAs 297:301 arg1 species 306:312 species 306:312 species belonging to five different families of the infra-order Ligiamorpha of terrestrial isopods 306:403 In this study, we amplified 12 new AGH cDNAs in species belonging to five different families of the infra-order Ligiamorpha of terrestrial isopods. 24561051 1 33 theme androgenic 90:99 arg1 AG 108:109 AG 108:109 AG 108:109 In crustaceans, the androgenic gland (AG), thanks to the synthesis of the androgenic gland hormone (AGH), controls the differentiation of the primary and secondary male sexual characters. 24561051 1 33 theme androgenic 90:99 arg1 gland 101:105 the androgenic gland 86:105 the androgenic gland (AG) 86:110 In crustaceans, the androgenic gland (AG), thanks to the synthesis of the androgenic gland hormone (AGH), controls the differentiation of the primary and secondary male sexual characters. 24561051 6 34 from Wolbachia 1132:1140 arg1 isopods 1191:1197 isopods 1191:1197 isopods 1191:1197 An in-depth understanding of the regulation of AGH expression would help deciphering the interaction between Wolbachia, widespread feminizing endosymbiotic bacteria in isopods, and the sex differentiation of their hosts. 24561051 1 35 theme hormone 161:167 arg1 synthesis 127:135 the synthesis 123:135 the synthesis of the androgenic gland hormone (AGH) 123:173 In crustaceans, the androgenic gland (AG), thanks to the synthesis of the androgenic gland hormone (AGH), controls the differentiation of the primary and secondary male sexual characters. 24561051 2 36 theme infra-order 358:368 arg1 Ligiamorpha 370:380 the infra-order Ligiamorpha 354:380 the infra-order Ligiamorpha of terrestrial isopods 354:403 In this study, we amplified 12 new AGH cDNAs in species belonging to five different families of the infra-order Ligiamorpha of terrestrial isopods. 24561051 1 37 theme sexual 239:244 arg1 characters 246:255 the primary and secondary male sexual characters 208:255 the primary and secondary male sexual characters 208:255 In crustaceans, the androgenic gland (AG), thanks to the synthesis of the androgenic gland hormone (AGH), controls the differentiation of the primary and secondary male sexual characters. 24561051 3 38 theme putative 601:608 arg1 motif 633:637 a putative N-linked glycosylation motif 599:637 a putative N-linked glycosylation motif on the A chains 599:653 Putative essential amino acids for the production of a functional AGH protein exhibit signatures of negative selection and are strictly conserved including typical proteolytic cleavage motifs, a putative N-linked glycosylation motif on the A chains and the eight Cys positions. 24561051 3 39 theme negative 506:513 arg1 selection 515:523 negative selection 506:523 negative selection 506:523 Putative essential amino acids for the production of a functional AGH protein exhibit signatures of negative selection and are strictly conserved including typical proteolytic cleavage motifs, a putative N-linked glycosylation motif on the A chains and the eight Cys positions. 24561051 3 40 theme essential 415:423 arg1 acids 431:435 Putative essential amino acids 406:435 Putative essential amino acids for the production of a functional AGH protein 406:482 Putative essential amino acids for the production of a functional AGH protein exhibit signatures of negative selection and are strictly conserved including typical proteolytic cleavage motifs, a putative N-linked glycosylation motif on the A chains and the eight Cys positions. 24561051 0 41 theme hormone 38:44 arg1 evolution 10:18 Molecular evolution 0:18 Molecular evolution of the androgenic hormone in terrestrial isopods 0:67 Molecular evolution of the androgenic hormone in terrestrial isopods. 24561051 1 42 theme characters 246:255 arg1 differentiation 189:203 the differentiation 185:203 the differentiation of the primary and secondary male sexual characters 185:255 In crustaceans, the androgenic gland (AG), thanks to the synthesis of the androgenic gland hormone (AGH), controls the differentiation of the primary and secondary male sexual characters. 24561051 3 43 theme N-linked 610:617 arg1 motif 633:637 a putative N-linked glycosylation motif 599:637 a putative N-linked glycosylation motif on the A chains 599:653 Putative essential amino acids for the production of a functional AGH protein exhibit signatures of negative selection and are strictly conserved including typical proteolytic cleavage motifs, a putative N-linked glycosylation motif on the A chains and the eight Cys positions. 24561051 6 44 theme hosts 1237:1241 arg1 bacteria 1179:1186 widespread feminizing endosymbiotic bacteria 1143:1186 widespread feminizing endosymbiotic bacteria in isopods 1143:1197 An in-depth understanding of the regulation of AGH expression would help deciphering the interaction between Wolbachia, widespread feminizing endosymbiotic bacteria in isopods, and the sex differentiation of their hosts. 24561051 6 44 theme hosts 1237:1241 arg1 Wolbachia 1132:1140 Wolbachia 1132:1140 Wolbachia 1132:1140 An in-depth understanding of the regulation of AGH expression would help deciphering the interaction between Wolbachia, widespread feminizing endosymbiotic bacteria in isopods, and the sex differentiation of their hosts. 24561051 6 44 theme hosts 1237:1241 arg1 differentiation 1212:1226 the sex differentiation 1204:1226 the sex differentiation of their hosts 1204:1241 An in-depth understanding of the regulation of AGH expression would help deciphering the interaction between Wolbachia, widespread feminizing endosymbiotic bacteria in isopods, and the sex differentiation of their hosts. 24561051 5 45 theme sequences 810:818 arg1 relationships 789:801 The phylogenetic relationships 772:801 The phylogenetic relationships of AGH sequences 772:818 The phylogenetic relationships of AGH sequences allowed one to distinguish two main clades, corresponding to members of the Armadillidiidae and the Porcellionidae families which are congruent with the narrow specificity of AG heterospecific grafting. 24561051 0 46 theme androgenic 27:36 arg1 hormone 38:44 the androgenic hormone 23:44 the androgenic hormone 23:44 Molecular evolution of the androgenic hormone in terrestrial isopods. 24561051 5 47 with congruent 954:962 arg1 specificity 980:990 the narrow specificity 969:990 the narrow specificity of AG heterospecific grafting 969:1020 The phylogenetic relationships of AGH sequences allowed one to distinguish two main clades, corresponding to members of the Armadillidiidae and the Porcellionidae families which are congruent with the narrow specificity of AG heterospecific grafting. 24561051 3 48 from positions 673:681 arg1 chains 648:653 the A chains 642:653 the A chains 642:653 Putative essential amino acids for the production of a functional AGH protein exhibit signatures of negative selection and are strictly conserved including typical proteolytic cleavage motifs, a putative N-linked glycosylation motif on the A chains and the eight Cys positions. 24561051 2 49 theme different 332:340 arg1 families 342:349 five different families 327:349 five different families of the infra-order Ligiamorpha of terrestrial isopods 327:403 In this study, we amplified 12 new AGH cDNAs in species belonging to five different families of the infra-order Ligiamorpha of terrestrial isopods. 24561051 0 50 theme terrestrial 49:59 arg1 isopods 61:67 terrestrial isopods 49:67 terrestrial isopods 49:67 Molecular evolution of the androgenic hormone in terrestrial isopods. 24561051 5 51 theme main 851:854 arg1 clades 856:861 two main clades 847:861 two main clades 847:861 The phylogenetic relationships of AGH sequences allowed one to distinguish two main clades, corresponding to members of the Armadillidiidae and the Porcellionidae families which are congruent with the narrow specificity of AG heterospecific grafting. 24561051 5 52 theme phylogenetic 776:787 arg1 relationships 789:801 The phylogenetic relationships 772:801 The phylogenetic relationships of AGH sequences 772:818 The phylogenetic relationships of AGH sequences allowed one to distinguish two main clades, corresponding to members of the Armadillidiidae and the Porcellionidae families which are congruent with the narrow specificity of AG heterospecific grafting. 24561051 2 53 theme isopods 397:403 arg1 Ligiamorpha 370:380 the infra-order Ligiamorpha 354:380 the infra-order Ligiamorpha of terrestrial isopods 354:403 In this study, we amplified 12 new AGH cDNAs in species belonging to five different families of the infra-order Ligiamorpha of terrestrial isopods. 24561051 5 54 theme grafting 1013:1020 arg1 specificity 980:990 the narrow specificity 969:990 the narrow specificity of AG heterospecific grafting 969:1020 The phylogenetic relationships of AGH sequences allowed one to distinguish two main clades, corresponding to members of the Armadillidiidae and the Porcellionidae families which are congruent with the narrow specificity of AG heterospecific grafting. 24561051 4 55 theme AGH 757:759 arg1 sequences 761:769 Armadillidium AGH sequences 743:769 Armadillidium AGH sequences 743:769 An insulin-like growth factor motif was also identified in Armadillidium AGH sequences. 24561051 4 56 theme Armadillidium 743:755 arg1 sequences 761:769 Armadillidium AGH sequences 743:769 Armadillidium AGH sequences 743:769 An insulin-like growth factor motif was also identified in Armadillidium AGH sequences. 24561051 3 57 theme cleavage 582:589 arg1 motifs 591:596 typical proteolytic cleavage motifs 562:596 typical proteolytic cleavage motifs 562:596 Putative essential amino acids for the production of a functional AGH protein exhibit signatures of negative selection and are strictly conserved including typical proteolytic cleavage motifs, a putative N-linked glycosylation motif on the A chains and the eight Cys positions. 24561051 5 58 theme AG 995:996 arg1 grafting 1013:1020 AG heterospecific grafting 995:1020 AG heterospecific grafting 995:1020 The phylogenetic relationships of AGH sequences allowed one to distinguish two main clades, corresponding to members of the Armadillidiidae and the Porcellionidae families which are congruent with the narrow specificity of AG heterospecific grafting. 24561051 3 59 theme amino 425:429 arg1 acids 431:435 Putative essential amino acids 406:435 Putative essential amino acids for the production of a functional AGH protein 406:482 Putative essential amino acids for the production of a functional AGH protein exhibit signatures of negative selection and are strictly conserved including typical proteolytic cleavage motifs, a putative N-linked glycosylation motif on the A chains and the eight Cys positions. 24561051 4 60 theme factor 707:712 arg1 motif 714:718 An insulin-like growth factor motif 684:718 An insulin-like growth factor motif 684:718 An insulin-like growth factor motif was also identified in Armadillidium AGH sequences. 24561051 6 61 theme endosymbiotic 1165:1177 arg1 bacteria 1179:1186 widespread feminizing endosymbiotic bacteria 1143:1186 widespread feminizing endosymbiotic bacteria in isopods 1143:1197 An in-depth understanding of the regulation of AGH expression would help deciphering the interaction between Wolbachia, widespread feminizing endosymbiotic bacteria in isopods, and the sex differentiation of their hosts. 24561051 3 62 theme glycosylation 619:631 arg1 motif 633:637 a putative N-linked glycosylation motif 599:637 a putative N-linked glycosylation motif on the A chains 599:653 Putative essential amino acids for the production of a functional AGH protein exhibit signatures of negative selection and are strictly conserved including typical proteolytic cleavage motifs, a putative N-linked glycosylation motif on the A chains and the eight Cys positions. 24561051 4 63 theme growth 700:705 arg1 factor 707:712 insulin-like growth factor 687:712 An insulin-like growth factor motif 684:718 An insulin-like growth factor motif was also identified in Armadillidium AGH sequences. 24561051 3 64 theme typical 562:568 arg1 motifs 591:596 typical proteolytic cleavage motifs 562:596 typical proteolytic cleavage motifs 562:596 Putative essential amino acids for the production of a functional AGH protein exhibit signatures of negative selection and are strictly conserved including typical proteolytic cleavage motifs, a putative N-linked glycosylation motif on the A chains and the eight Cys positions. 24561051 3 65 theme Putative 406:413 arg1 acids 431:435 Putative essential amino acids 406:435 Putative essential amino acids for the production of a functional AGH protein 406:482 Putative essential amino acids for the production of a functional AGH protein exhibit signatures of negative selection and are strictly conserved including typical proteolytic cleavage motifs, a putative N-linked glycosylation motif on the A chains and the eight Cys positions. 24561051 5 66 theme Porcellionidae 920:933 arg1 families 935:942 the Armadillidiidae and the Porcellionidae families 892:942 the Armadillidiidae and the Porcellionidae families which are congruent with the narrow specificity of AG heterospecific grafting 892:1020 The phylogenetic relationships of AGH sequences allowed one to distinguish two main clades, corresponding to members of the Armadillidiidae and the Porcellionidae families which are congruent with the narrow specificity of AG heterospecific grafting. 24561051 5 66 theme Porcellionidae 920:933 arg1 congruent 954:962 congruent 954:962 congruent 954:962 The phylogenetic relationships of AGH sequences allowed one to distinguish two main clades, corresponding to members of the Armadillidiidae and the Porcellionidae families which are congruent with the narrow specificity of AG heterospecific grafting. 24561051 6 67 theme regulation 1056:1065 arg1 understanding 1035:1047 An in-depth understanding 1023:1047 An in-depth understanding of the regulation of AGH expression 1023:1083 An in-depth understanding of the regulation of AGH expression would help deciphering the interaction between Wolbachia, widespread feminizing endosymbiotic bacteria in isopods, and the sex differentiation of their hosts. 24561051 3 68 from motif 633:637 arg1 chains 648:653 the A chains 642:653 the A chains 642:653 Putative essential amino acids for the production of a functional AGH protein exhibit signatures of negative selection and are strictly conserved including typical proteolytic cleavage motifs, a putative N-linked glycosylation motif on the A chains and the eight Cys positions. 24561051 3 69 theme proteolytic 570:580 arg1 motifs 591:596 typical proteolytic cleavage motifs 562:596 typical proteolytic cleavage motifs 562:596 Putative essential amino acids for the production of a functional AGH protein exhibit signatures of negative selection and are strictly conserved including typical proteolytic cleavage motifs, a putative N-linked glycosylation motif on the A chains and the eight Cys positions. 24561051 3 70 theme functional 461:470 arg1 protein 476:482 a functional AGH protein 459:482 a functional AGH protein 459:482 Putative essential amino acids for the production of a functional AGH protein exhibit signatures of negative selection and are strictly conserved including typical proteolytic cleavage motifs, a putative N-linked glycosylation motif on the A chains and the eight Cys positions. 24561051 3 71 gly glycosylation 619:631 arg2 motif 633:637 a putative N-linked glycosylation motif 599:637 a putative N-linked glycosylation motif on the A chains 599:653 Putative essential amino acids for the production of a functional AGH protein exhibit signatures of negative selection and are strictly conserved including typical proteolytic cleavage motifs, a putative N-linked glycosylation motif on the A chains and the eight Cys positions. 29042437 5 0 dep processing 798:807 arg1 the 794:796 the 794:796 the 794:796 We herein investigated the processing and membrane translocation of Mid1. 29042437 10 1 theme wild-type 1567:1575 arg1 Mid1 1577:1580 wild-type Mid1 1567:1580 wild-type Mid1 1567:1580 In the sec71Δ and sec72Δ single mutants defective in the post-translational protein transport into the endoplasmic reticulum (ER), Mid1ΔN23 could not mediate Ca2+ influx and did not undergo N-glycosylation, whereas wild-type Mid1 exhibited normal Ca2+ influx activity and N-glycosylation in these mutants. 29042437 11 2 theme signal 1673:1678 arg1 protein 1705:1711 the signal peptide-lacking Mid1ΔN23 protein 1669:1711 the signal peptide-lacking Mid1ΔN23 protein 1669:1711 Therefore, the signal peptide-lacking Mid1ΔN23 protein may be translocated to the ER exclusively through the post-translational protein translocation, which typically requires an N-terminal signal peptide. 29042437 6 3 theme N-terminal 889:898 arg1 peptide 907:913 a 20-amino-acid-long N-terminal signal peptide 868:913 a 20-amino-acid-long N-terminal signal peptide 868:913 Mid1 was found to have a 20-amino-acid-long N-terminal signal peptide and appeared to be entirely localized extracellularly. 29042437 10 4 theme protein 1428:1434 arg1 transport 1436:1444 the post-translational protein transport 1405:1444 the post-translational protein transport into the endoplasmic reticulum (ER) 1405:1480 In the sec71Δ and sec72Δ single mutants defective in the post-translational protein transport into the endoplasmic reticulum (ER), Mid1ΔN23 could not mediate Ca2+ influx and did not undergo N-glycosylation, whereas wild-type Mid1 exhibited normal Ca2+ influx activity and N-glycosylation in these mutants. 29042437 1 5 theme pore-forming 262:273 arg1 family 303:308 the eukaryotic pore-forming, four-domain cation channel family 247:308 the eukaryotic pore-forming, four-domain cation channel family 247:308 Saccharomyces cerevisiae Mid1 is composed of 548 amino acids and a regulatory subunit of Cch1, a member of the eukaryotic pore-forming, four-domain cation channel family. 29042437 8 6 theme amino 1187:1191 arg1 residues 1198:1205 209 N-terminal amino acid residues 1172:1205 209 N-terminal amino acid residues 1172:1205 Moreover, an N-terminal truncation analysis revealed that even truncated Mid1 lacking 209 N-terminal amino acid residues was N-glycosylated and maintained Ca2+ influx activity. 29042437 10 7 theme Ca2+ 1599:1602 arg1 influx 1604:1609 normal Ca2+ influx 1592:1609 normal Ca2+ influx activity 1592:1618 In the sec71Δ and sec72Δ single mutants defective in the post-translational protein transport into the endoplasmic reticulum (ER), Mid1ΔN23 could not mediate Ca2+ influx and did not undergo N-glycosylation, whereas wild-type Mid1 exhibited normal Ca2+ influx activity and N-glycosylation in these mutants. 29042437 1 8 theme amino 189:193 arg1 acids 195:199 548 amino acids 185:199 548 amino acids 185:199 Saccharomyces cerevisiae Mid1 is composed of 548 amino acids and a regulatory subunit of Cch1, a member of the eukaryotic pore-forming, four-domain cation channel family. 29042437 10 9 gly N-glycosylation 1542:1556 arg1 Mid1ΔN23 1483:1490 Mid1ΔN23 1483:1490 Mid1ΔN23 1483:1490 In the sec71Δ and sec72Δ single mutants defective in the post-translational protein transport into the endoplasmic reticulum (ER), Mid1ΔN23 could not mediate Ca2+ influx and did not undergo N-glycosylation, whereas wild-type Mid1 exhibited normal Ca2+ influx activity and N-glycosylation in these mutants. 29042437 10 10 theme endoplasmic 1455:1465 arg1 ER 1478:1479 ER 1478:1479 ER 1478:1479 In the sec71Δ and sec72Δ single mutants defective in the post-translational protein transport into the endoplasmic reticulum (ER), Mid1ΔN23 could not mediate Ca2+ influx and did not undergo N-glycosylation, whereas wild-type Mid1 exhibited normal Ca2+ influx activity and N-glycosylation in these mutants. 29042437 10 10 theme endoplasmic 1455:1465 arg1 reticulum 1467:1475 the endoplasmic reticulum 1451:1475 the endoplasmic reticulum (ER) 1451:1480 In the sec71Δ and sec72Δ single mutants defective in the post-translational protein transport into the endoplasmic reticulum (ER), Mid1ΔN23 could not mediate Ca2+ influx and did not undergo N-glycosylation, whereas wild-type Mid1 exhibited normal Ca2+ influx activity and N-glycosylation in these mutants. 29042437 3 11 theme sequence 534:541 arg1 similarity 543:552 overall primary sequence similarity 518:552 overall primary sequence similarity 518:552 Despite a lack in overall primary sequence similarity, Mid1 resembles in some aspects VGCC α2/δ regulatory subunits and NALCN-associated proteins. 29042437 0 12 theme family 132:137 arg1 subunit 86:92 the yeast regulatory Mid1 subunit 60:92 the yeast regulatory Mid1 subunit of the Cch1/VGCC/NALCN cation channel family 60:137 Post-translational processing and membrane translocation of the yeast regulatory Mid1 subunit of the Cch1/VGCC/NALCN cation channel family. 29042437 3 13 theme overall 518:524 arg1 similarity 543:552 overall primary sequence similarity 518:552 overall primary sequence similarity 518:552 Despite a lack in overall primary sequence similarity, Mid1 resembles in some aspects VGCC α2/δ regulatory subunits and NALCN-associated proteins. 29042437 1 14 theme regulatory 207:216 arg1 member 237:242 a member 235:242 a member of the eukaryotic pore-forming, four-domain cation channel family 235:308 Saccharomyces cerevisiae Mid1 is composed of 548 amino acids and a regulatory subunit of Cch1, a member of the eukaryotic pore-forming, four-domain cation channel family. 29042437 1 14 theme regulatory 207:216 arg1 subunit 218:224 a regulatory subunit 205:224 a regulatory subunit of Cch1 205:232 Saccharomyces cerevisiae Mid1 is composed of 548 amino acids and a regulatory subunit of Cch1, a member of the eukaryotic pore-forming, four-domain cation channel family. 29042437 5 15 theme Mid1 839:842 arg1 processing 798:807 processing 798:807 processing 798:807 We herein investigated the processing and membrane translocation of Mid1. 29042437 5 15 theme Mid1 839:842 arg1 translocation 822:834 membrane translocation 813:834 membrane translocation 813:834 We herein investigated the processing and membrane translocation of Mid1. 29042437 8 16 theme influx 1246:1251 arg1 activity 1253:1260 Ca2+ influx activity 1241:1260 Ca2+ influx activity 1241:1260 Moreover, an N-terminal truncation analysis revealed that even truncated Mid1 lacking 209 N-terminal amino acid residues was N-glycosylated and maintained Ca2+ influx activity. 29042437 7 17 theme Ca2+ 1051:1054 arg1 influx 1056:1061 Ca2+ influx 1051:1061 Ca2+ influx activity 1051:1070 A signal peptide-deleted Mid1 protein, Mid1ΔN23, was N-glycosylated and retained Ca2+ influx activity through Cch1. 29042437 9 18 theme Mid1 1290:1293 arg1 protein 1295:1301 A 219-amino-acid-truncated Mid1 protein 1263:1301 A 219-amino-acid-truncated Mid1 protein 1263:1301 A 219-amino-acid-truncated Mid1 protein lost this activity but was still N-glycosylated. 29042437 1 19 dep pore-forming 262:273 arg1 four-domain 276:286 four-domain 276:286 four-domain 276:286 Saccharomyces cerevisiae Mid1 is composed of 548 amino acids and a regulatory subunit of Cch1, a member of the eukaryotic pore-forming, four-domain cation channel family. 29042437 7 20 theme Mid1 995:998 arg1 Mid1ΔN23 1009:1016 Mid1ΔN23 1009:1016 Mid1ΔN23 1009:1016 A signal peptide-deleted Mid1 protein, Mid1ΔN23, was N-glycosylated and retained Ca2+ influx activity through Cch1. 29042437 7 20 theme Mid1 995:998 arg1 N-glycosylated 1023:1036 N-glycosylated 1023:1036 N-glycosylated 1023:1036 A signal peptide-deleted Mid1 protein, Mid1ΔN23, was N-glycosylated and retained Ca2+ influx activity through Cch1. 29042437 7 20 theme Mid1 995:998 arg1 protein 1000:1006 A signal peptide-deleted Mid1 protein 970:1006 A signal peptide-deleted Mid1 protein 970:1006 A signal peptide-deleted Mid1 protein, Mid1ΔN23, was N-glycosylated and retained Ca2+ influx activity through Cch1. 29042437 2 21 theme Ca2+ 477:480 arg1 VGCCs 492:496 VGCCs 492:496 VGCCs 492:496 The amino acid sequence and voltage insensitivity of Cch1 are more similar to those of Na+ leak channel non-selective (NALCN) than to the α1 subunit of voltage-gated Ca2+ channels (VGCCs). 29042437 2 21 theme Ca2+ 477:480 arg1 channels 482:489 voltage-gated Ca2+ channels 463:489 voltage-gated Ca2+ channels (VGCCs) 463:497 The amino acid sequence and voltage insensitivity of Cch1 are more similar to those of Na+ leak channel non-selective (NALCN) than to the α1 subunit of voltage-gated Ca2+ channels (VGCCs). 29042437 4 22 theme α2/δ 661:664 arg1 subunits 666:673 animal α2/δ subunits 654:673 animal α2/δ subunits 654:673 Unlike animal α2/δ subunits, Mid1 and NALCN-associated proteins are essential for the function of the pore-forming subunit. 29042437 0 23 theme regulatory 70:79 arg1 subunit 86:92 the yeast regulatory Mid1 subunit 60:92 the yeast regulatory Mid1 subunit of the Cch1/VGCC/NALCN cation channel family 60:137 Post-translational processing and membrane translocation of the yeast regulatory Mid1 subunit of the Cch1/VGCC/NALCN cation channel family. 29042437 7 24 theme signal 972:977 arg1 Mid1ΔN23 1009:1016 Mid1ΔN23 1009:1016 Mid1ΔN23 1009:1016 A signal peptide-deleted Mid1 protein, Mid1ΔN23, was N-glycosylated and retained Ca2+ influx activity through Cch1. 29042437 7 24 theme signal 972:977 arg1 N-glycosylated 1023:1036 N-glycosylated 1023:1036 N-glycosylated 1023:1036 A signal peptide-deleted Mid1 protein, Mid1ΔN23, was N-glycosylated and retained Ca2+ influx activity through Cch1. 29042437 7 24 theme signal 972:977 arg1 protein 1000:1006 A signal peptide-deleted Mid1 protein 970:1006 A signal peptide-deleted Mid1 protein 970:1006 A signal peptide-deleted Mid1 protein, Mid1ΔN23, was N-glycosylated and retained Ca2+ influx activity through Cch1. 29042437 11 25 theme signal 1848:1853 arg1 peptide 1855:1861 an N-terminal signal peptide 1834:1861 an N-terminal signal peptide 1834:1861 Therefore, the signal peptide-lacking Mid1ΔN23 protein may be translocated to the ER exclusively through the post-translational protein translocation, which typically requires an N-terminal signal peptide. 29042437 0 26 theme subunit 86:92 arg1 processing 19:28 Post-translational processing 0:28 Post-translational processing 0:28 Post-translational processing and membrane translocation of the yeast regulatory Mid1 subunit of the Cch1/VGCC/NALCN cation channel family. 29042437 0 26 theme subunit 86:92 arg1 translocation 43:55 membrane translocation 34:55 membrane translocation 34:55 Post-translational processing and membrane translocation of the yeast regulatory Mid1 subunit of the Cch1/VGCC/NALCN cation channel family. 29042437 1 27 dep Saccharomyces 140:152 arg1 cerevisiae 154:163 cerevisiae 154:163 cerevisiae 154:163 Saccharomyces cerevisiae Mid1 is composed of 548 amino acids and a regulatory subunit of Cch1, a member of the eukaryotic pore-forming, four-domain cation channel family. 29042437 3 28 from lack 510:513 arg1 similarity 543:552 overall primary sequence similarity 518:552 overall primary sequence similarity 518:552 Despite a lack in overall primary sequence similarity, Mid1 resembles in some aspects VGCC α2/δ regulatory subunits and NALCN-associated proteins. 29042437 7 29 gly N-glycosylated 1023:1036 arg1 Mid1ΔN23 1009:1016 Mid1ΔN23 1009:1016 Mid1ΔN23 1009:1016 A signal peptide-deleted Mid1 protein, Mid1ΔN23, was N-glycosylated and retained Ca2+ influx activity through Cch1. 29042437 7 29 gly N-glycosylated 1023:1036 arg1 N-glycosylated 1023:1036 N-glycosylated 1023:1036 N-glycosylated 1023:1036 A signal peptide-deleted Mid1 protein, Mid1ΔN23, was N-glycosylated and retained Ca2+ influx activity through Cch1. 29042437 7 29 gly N-glycosylated 1023:1036 arg1 protein 1000:1006 A signal peptide-deleted Mid1 protein 970:1006 A signal peptide-deleted Mid1 protein 970:1006 A signal peptide-deleted Mid1 protein, Mid1ΔN23, was N-glycosylated and retained Ca2+ influx activity through Cch1. 29042437 10 30 theme Ca2+ 1510:1513 arg1 influx 1515:1520 Ca2+ influx 1510:1520 Ca2+ influx 1510:1520 In the sec71Δ and sec72Δ single mutants defective in the post-translational protein transport into the endoplasmic reticulum (ER), Mid1ΔN23 could not mediate Ca2+ influx and did not undergo N-glycosylation, whereas wild-type Mid1 exhibited normal Ca2+ influx activity and N-glycosylation in these mutants. 29042437 4 31 theme pore-forming 749:760 arg1 subunit 762:768 the pore-forming subunit 745:768 the pore-forming subunit 745:768 Unlike animal α2/δ subunits, Mid1 and NALCN-associated proteins are essential for the function of the pore-forming subunit. 29042437 0 32 theme cation 117:122 arg1 family 132:137 the Cch1/VGCC/NALCN cation channel family 97:137 the Cch1/VGCC/NALCN cation channel family 97:137 Post-translational processing and membrane translocation of the yeast regulatory Mid1 subunit of the Cch1/VGCC/NALCN cation channel family. 29042437 0 33 theme Post-translational 0:17 arg1 processing 19:28 Post-translational processing 0:28 Post-translational processing 0:28 Post-translational processing and membrane translocation of the yeast regulatory Mid1 subunit of the Cch1/VGCC/NALCN cation channel family. 29042437 10 34 theme post-translational 1409:1426 arg1 transport 1436:1444 the post-translational protein transport 1405:1444 the post-translational protein transport into the endoplasmic reticulum (ER) 1405:1480 In the sec71Δ and sec72Δ single mutants defective in the post-translational protein transport into the endoplasmic reticulum (ER), Mid1ΔN23 could not mediate Ca2+ influx and did not undergo N-glycosylation, whereas wild-type Mid1 exhibited normal Ca2+ influx activity and N-glycosylation in these mutants. 29042437 1 35 theme cation 288:293 arg1 family 303:308 the eukaryotic pore-forming, four-domain cation channel family 247:308 the eukaryotic pore-forming, four-domain cation channel family 247:308 Saccharomyces cerevisiae Mid1 is composed of 548 amino acids and a regulatory subunit of Cch1, a member of the eukaryotic pore-forming, four-domain cation channel family. 29042437 2 36 theme α1 449:450 arg1 subunit 452:458 the α1 subunit 445:458 the α1 subunit of voltage-gated Ca2+ channels (VGCCs) 445:497 The amino acid sequence and voltage insensitivity of Cch1 are more similar to those of Na+ leak channel non-selective (NALCN) than to the α1 subunit of voltage-gated Ca2+ channels (VGCCs). 29042437 2 37 theme Na+ 398:400 arg1 NALCN 430:434 NALCN 430:434 NALCN 430:434 The amino acid sequence and voltage insensitivity of Cch1 are more similar to those of Na+ leak channel non-selective (NALCN) than to the α1 subunit of voltage-gated Ca2+ channels (VGCCs). 29042437 2 37 theme Na+ 398:400 arg1 channel 407:413 Na+ leak channel non-selective 398:427 Na+ leak channel non-selective (NALCN) 398:435 The amino acid sequence and voltage insensitivity of Cch1 are more similar to those of Na+ leak channel non-selective (NALCN) than to the α1 subunit of voltage-gated Ca2+ channels (VGCCs). 29042437 1 38 theme family 303:308 arg1 member 237:242 a member 235:242 a member of the eukaryotic pore-forming, four-domain cation channel family 235:308 Saccharomyces cerevisiae Mid1 is composed of 548 amino acids and a regulatory subunit of Cch1, a member of the eukaryotic pore-forming, four-domain cation channel family. 29042437 1 38 theme family 303:308 arg1 subunit 218:224 a regulatory subunit 205:224 a regulatory subunit of Cch1 205:232 Saccharomyces cerevisiae Mid1 is composed of 548 amino acids and a regulatory subunit of Cch1, a member of the eukaryotic pore-forming, four-domain cation channel family. 29042437 3 39 theme regulatory 596:605 arg1 subunits 607:614 regulatory subunits 596:614 regulatory subunits 596:614 Despite a lack in overall primary sequence similarity, Mid1 resembles in some aspects VGCC α2/δ regulatory subunits and NALCN-associated proteins. 29042437 10 40 theme sec72Δ 1370:1375 arg1 mutants 1384:1390 the sec71Δ and sec72Δ single mutants 1355:1390 mutants 1384:1390 In the sec71Δ and sec72Δ single mutants defective in the post-translational protein transport into the endoplasmic reticulum (ER), Mid1ΔN23 could not mediate Ca2+ influx and did not undergo N-glycosylation, whereas wild-type Mid1 exhibited normal Ca2+ influx activity and N-glycosylation in these mutants. 29042437 2 41 theme voltage 339:345 arg1 insensitivity 347:359 voltage insensitivity 339:359 voltage insensitivity of Cch1 339:367 The amino acid sequence and voltage insensitivity of Cch1 are more similar to those of Na+ leak channel non-selective (NALCN) than to the α1 subunit of voltage-gated Ca2+ channels (VGCCs). 29042437 8 42 theme N-terminal 1099:1108 arg1 analysis 1121:1128 an N-terminal truncation analysis 1096:1128 an N-terminal truncation analysis 1096:1128 Moreover, an N-terminal truncation analysis revealed that even truncated Mid1 lacking 209 N-terminal amino acid residues was N-glycosylated and maintained Ca2+ influx activity. 29042437 1 43 theme Cch1 229:232 arg1 acids 195:199 548 amino acids 185:199 548 amino acids 185:199 Saccharomyces cerevisiae Mid1 is composed of 548 amino acids and a regulatory subunit of Cch1, a member of the eukaryotic pore-forming, four-domain cation channel family. 29042437 1 43 theme Cch1 229:232 arg1 member 237:242 a member 235:242 a member of the eukaryotic pore-forming, four-domain cation channel family 235:308 Saccharomyces cerevisiae Mid1 is composed of 548 amino acids and a regulatory subunit of Cch1, a member of the eukaryotic pore-forming, four-domain cation channel family. 29042437 1 43 theme Cch1 229:232 arg1 subunit 218:224 a regulatory subunit 205:224 a regulatory subunit of Cch1 205:232 Saccharomyces cerevisiae Mid1 is composed of 548 amino acids and a regulatory subunit of Cch1, a member of the eukaryotic pore-forming, four-domain cation channel family. 29042437 12 44 theme protein 1915:1921 arg1 translocation 1923:1935 protein translocation 1915:1935 protein translocation 1915:1935 Mid1 may provide a tool for studying mechanisms of protein translocation into the ER. 29042437 10 45 from transport 1436:1444 arg1 defective 1392:1400 defective 1392:1400 defective 1392:1400 In the sec71Δ and sec72Δ single mutants defective in the post-translational protein transport into the endoplasmic reticulum (ER), Mid1ΔN23 could not mediate Ca2+ influx and did not undergo N-glycosylation, whereas wild-type Mid1 exhibited normal Ca2+ influx activity and N-glycosylation in these mutants. 29042437 10 46 theme normal 1592:1597 arg1 influx 1604:1609 normal Ca2+ influx 1592:1609 normal Ca2+ influx activity 1592:1618 In the sec71Δ and sec72Δ single mutants defective in the post-translational protein transport into the endoplasmic reticulum (ER), Mid1ΔN23 could not mediate Ca2+ influx and did not undergo N-glycosylation, whereas wild-type Mid1 exhibited normal Ca2+ influx activity and N-glycosylation in these mutants. 29042437 11 47 theme post-translational 1767:1784 arg1 translocation 1794:1806 the post-translational protein translocation 1763:1806 the post-translational protein translocation 1763:1806 Therefore, the signal peptide-lacking Mid1ΔN23 protein may be translocated to the ER exclusively through the post-translational protein translocation, which typically requires an N-terminal signal peptide. 29042437 8 48 theme truncated 1149:1157 arg1 Mid1 1159:1162 even truncated Mid1 1144:1162 even truncated Mid1 lacking 209 N-terminal amino acid residues 1144:1205 Moreover, an N-terminal truncation analysis revealed that even truncated Mid1 lacking 209 N-terminal amino acid residues was N-glycosylated and maintained Ca2+ influx activity. 29042437 6 49 theme signal 900:905 arg1 peptide 907:913 a 20-amino-acid-long N-terminal signal peptide 868:913 a 20-amino-acid-long N-terminal signal peptide 868:913 Mid1 was found to have a 20-amino-acid-long N-terminal signal peptide and appeared to be entirely localized extracellularly. 29042437 11 50 theme peptide-lacking 1680:1694 arg1 protein 1705:1711 the signal peptide-lacking Mid1ΔN23 protein 1669:1711 the signal peptide-lacking Mid1ΔN23 protein 1669:1711 Therefore, the signal peptide-lacking Mid1ΔN23 protein may be translocated to the ER exclusively through the post-translational protein translocation, which typically requires an N-terminal signal peptide. 29042437 1 51 theme eukaryotic 251:260 arg1 family 303:308 the eukaryotic pore-forming, four-domain cation channel family 247:308 the eukaryotic pore-forming, four-domain cation channel family 247:308 Saccharomyces cerevisiae Mid1 is composed of 548 amino acids and a regulatory subunit of Cch1, a member of the eukaryotic pore-forming, four-domain cation channel family. 29042437 2 52 theme amino 315:319 arg1 sequence 326:333 The amino acid sequence 311:333 The amino acid sequence 311:333 The amino acid sequence and voltage insensitivity of Cch1 are more similar to those of Na+ leak channel non-selective (NALCN) than to the α1 subunit of voltage-gated Ca2+ channels (VGCCs). 29042437 2 52 theme amino 315:319 arg1 similar 378:384 similar 378:384 similar 378:384 The amino acid sequence and voltage insensitivity of Cch1 are more similar to those of Na+ leak channel non-selective (NALCN) than to the α1 subunit of voltage-gated Ca2+ channels (VGCCs). 29042437 6 53 theme 20-amino-acid-long 870:887 arg1 peptide 907:913 a 20-amino-acid-long N-terminal signal peptide 868:913 a 20-amino-acid-long N-terminal signal peptide 868:913 Mid1 was found to have a 20-amino-acid-long N-terminal signal peptide and appeared to be entirely localized extracellularly. 29042437 10 54 theme influx 1604:1609 arg1 activity 1611:1618 normal Ca2+ influx activity 1592:1618 normal Ca2+ influx activity 1592:1618 In the sec71Δ and sec72Δ single mutants defective in the post-translational protein transport into the endoplasmic reticulum (ER), Mid1ΔN23 could not mediate Ca2+ influx and did not undergo N-glycosylation, whereas wild-type Mid1 exhibited normal Ca2+ influx activity and N-glycosylation in these mutants. 29042437 8 55 gly N-glycosylated 1211:1224 arg1 Mid1 1159:1162 even truncated Mid1 1144:1162 even truncated Mid1 lacking 209 N-terminal amino acid residues 1144:1205 Moreover, an N-terminal truncation analysis revealed that even truncated Mid1 lacking 209 N-terminal amino acid residues was N-glycosylated and maintained Ca2+ influx activity. 29042437 8 56 theme N-terminal 1176:1185 arg1 residues 1198:1205 209 N-terminal amino acid residues 1172:1205 209 N-terminal amino acid residues 1172:1205 Moreover, an N-terminal truncation analysis revealed that even truncated Mid1 lacking 209 N-terminal amino acid residues was N-glycosylated and maintained Ca2+ influx activity. 29042437 3 57 theme primary 526:532 arg1 similarity 543:552 overall primary sequence similarity 518:552 overall primary sequence similarity 518:552 Despite a lack in overall primary sequence similarity, Mid1 resembles in some aspects VGCC α2/δ regulatory subunits and NALCN-associated proteins. 29042437 8 58 theme acid 1193:1196 arg1 residues 1198:1205 209 N-terminal amino acid residues 1172:1205 209 N-terminal amino acid residues 1172:1205 Moreover, an N-terminal truncation analysis revealed that even truncated Mid1 lacking 209 N-terminal amino acid residues was N-glycosylated and maintained Ca2+ influx activity. 29042437 5 59 theme membrane 813:820 arg1 translocation 822:834 membrane translocation 813:834 membrane translocation 813:834 We herein investigated the processing and membrane translocation of Mid1. 29042437 6 60 contain have 863:866 arg1 Mid1 845:848 Mid1 845:848 Mid1 845:848 Mid1 was found to have a 20-amino-acid-long N-terminal signal peptide and appeared to be entirely localized extracellularly. 29042437 6 60 contain have 863:866 arg2 peptide 907:913 a 20-amino-acid-long N-terminal signal peptide 868:913 a 20-amino-acid-long N-terminal signal peptide 868:913 Mid1 was found to have a 20-amino-acid-long N-terminal signal peptide and appeared to be entirely localized extracellularly. 29042437 7 61 theme influx 1056:1061 arg1 activity 1063:1070 Ca2+ influx activity 1051:1070 Ca2+ influx activity 1051:1070 A signal peptide-deleted Mid1 protein, Mid1ΔN23, was N-glycosylated and retained Ca2+ influx activity through Cch1. 29042437 3 62 dep aspects 578:584 arg1 VGCC 586:589 VGCC 586:589 VGCC 586:589 Despite a lack in overall primary sequence similarity, Mid1 resembles in some aspects VGCC α2/δ regulatory subunits and NALCN-associated proteins. 29042437 9 63 theme 219-amino-acid-truncated 1265:1288 arg1 protein 1295:1301 A 219-amino-acid-truncated Mid1 protein 1263:1301 A 219-amino-acid-truncated Mid1 protein 1263:1301 A 219-amino-acid-truncated Mid1 protein lost this activity but was still N-glycosylated. 29042437 8 64 theme Ca2+ 1241:1244 arg1 influx 1246:1251 Ca2+ influx 1241:1251 Ca2+ influx activity 1241:1260 Moreover, an N-terminal truncation analysis revealed that even truncated Mid1 lacking 209 N-terminal amino acid residues was N-glycosylated and maintained Ca2+ influx activity. 29042437 1 65 theme Saccharomyces 140:152 arg1 Mid1 165:168 Saccharomyces cerevisiae Mid1 140:168 Saccharomyces cerevisiae Mid1 140:168 Saccharomyces cerevisiae Mid1 is composed of 548 amino acids and a regulatory subunit of Cch1, a member of the eukaryotic pore-forming, four-domain cation channel family. 29042437 4 66 theme NALCN-associated 685:700 arg1 proteins 702:709 NALCN-associated proteins 685:709 NALCN-associated proteins 685:709 Unlike animal α2/δ subunits, Mid1 and NALCN-associated proteins are essential for the function of the pore-forming subunit. 29042437 0 67 theme Mid1 81:84 arg1 subunit 86:92 the yeast regulatory Mid1 subunit 60:92 the yeast regulatory Mid1 subunit of the Cch1/VGCC/NALCN cation channel family 60:137 Post-translational processing and membrane translocation of the yeast regulatory Mid1 subunit of the Cch1/VGCC/NALCN cation channel family. 29042437 2 68 theme voltage-gated 463:475 arg1 VGCCs 492:496 VGCCs 492:496 VGCCs 492:496 The amino acid sequence and voltage insensitivity of Cch1 are more similar to those of Na+ leak channel non-selective (NALCN) than to the α1 subunit of voltage-gated Ca2+ channels (VGCCs). 29042437 2 68 theme voltage-gated 463:475 arg1 channels 482:489 voltage-gated Ca2+ channels 463:489 voltage-gated Ca2+ channels (VGCCs) 463:497 The amino acid sequence and voltage insensitivity of Cch1 are more similar to those of Na+ leak channel non-selective (NALCN) than to the α1 subunit of voltage-gated Ca2+ channels (VGCCs). 29042437 4 69 theme animal 654:659 arg1 subunits 666:673 animal α2/δ subunits 654:673 animal α2/δ subunits 654:673 Unlike animal α2/δ subunits, Mid1 and NALCN-associated proteins are essential for the function of the pore-forming subunit. 29042437 7 70 theme peptide-deleted 979:993 arg1 Mid1ΔN23 1009:1016 Mid1ΔN23 1009:1016 Mid1ΔN23 1009:1016 A signal peptide-deleted Mid1 protein, Mid1ΔN23, was N-glycosylated and retained Ca2+ influx activity through Cch1. 29042437 7 70 theme peptide-deleted 979:993 arg1 N-glycosylated 1023:1036 N-glycosylated 1023:1036 N-glycosylated 1023:1036 A signal peptide-deleted Mid1 protein, Mid1ΔN23, was N-glycosylated and retained Ca2+ influx activity through Cch1. 29042437 7 70 theme peptide-deleted 979:993 arg1 protein 1000:1006 A signal peptide-deleted Mid1 protein 970:1006 A signal peptide-deleted Mid1 protein 970:1006 A signal peptide-deleted Mid1 protein, Mid1ΔN23, was N-glycosylated and retained Ca2+ influx activity through Cch1. 29042437 0 71 theme Cch1/VGCC/NALCN 101:115 arg1 family 132:137 the Cch1/VGCC/NALCN cation channel family 97:137 the Cch1/VGCC/NALCN cation channel family 97:137 Post-translational processing and membrane translocation of the yeast regulatory Mid1 subunit of the Cch1/VGCC/NALCN cation channel family. 29042437 11 72 theme N-terminal 1837:1846 arg1 peptide 1855:1861 an N-terminal signal peptide 1834:1861 an N-terminal signal peptide 1834:1861 Therefore, the signal peptide-lacking Mid1ΔN23 protein may be translocated to the ER exclusively through the post-translational protein translocation, which typically requires an N-terminal signal peptide. 29042437 0 73 theme channel 124:130 arg1 family 132:137 the Cch1/VGCC/NALCN cation channel family 97:137 the Cch1/VGCC/NALCN cation channel family 97:137 Post-translational processing and membrane translocation of the yeast regulatory Mid1 subunit of the Cch1/VGCC/NALCN cation channel family. 29042437 2 74 theme channels 482:489 arg1 subunit 452:458 the α1 subunit 445:458 the α1 subunit of voltage-gated Ca2+ channels (VGCCs) 445:497 The amino acid sequence and voltage insensitivity of Cch1 are more similar to those of Na+ leak channel non-selective (NALCN) than to the α1 subunit of voltage-gated Ca2+ channels (VGCCs). 29042437 10 75 gly N-glycosylation 1624:1638 arg1 mutants 1649:1655 these mutants 1643:1655 these mutants 1643:1655 In the sec71Δ and sec72Δ single mutants defective in the post-translational protein transport into the endoplasmic reticulum (ER), Mid1ΔN23 could not mediate Ca2+ influx and did not undergo N-glycosylation, whereas wild-type Mid1 exhibited normal Ca2+ influx activity and N-glycosylation in these mutants. 29042437 0 76 theme membrane 34:41 arg1 translocation 43:55 membrane translocation 34:55 membrane translocation 34:55 Post-translational processing and membrane translocation of the yeast regulatory Mid1 subunit of the Cch1/VGCC/NALCN cation channel family. 29042437 10 77 from defective 1392:1400 arg1 transport 1436:1444 the post-translational protein transport 1405:1444 the post-translational protein transport into the endoplasmic reticulum (ER) 1405:1480 In the sec71Δ and sec72Δ single mutants defective in the post-translational protein transport into the endoplasmic reticulum (ER), Mid1ΔN23 could not mediate Ca2+ influx and did not undergo N-glycosylation, whereas wild-type Mid1 exhibited normal Ca2+ influx activity and N-glycosylation in these mutants. 29042437 2 78 theme non-selective 415:427 arg1 NALCN 430:434 NALCN 430:434 NALCN 430:434 The amino acid sequence and voltage insensitivity of Cch1 are more similar to those of Na+ leak channel non-selective (NALCN) than to the α1 subunit of voltage-gated Ca2+ channels (VGCCs). 29042437 2 78 theme non-selective 415:427 arg1 channel 407:413 Na+ leak channel non-selective 398:427 Na+ leak channel non-selective (NALCN) 398:435 The amino acid sequence and voltage insensitivity of Cch1 are more similar to those of Na+ leak channel non-selective (NALCN) than to the α1 subunit of voltage-gated Ca2+ channels (VGCCs). 29042437 2 79 theme leak 402:405 arg1 NALCN 430:434 NALCN 430:434 NALCN 430:434 The amino acid sequence and voltage insensitivity of Cch1 are more similar to those of Na+ leak channel non-selective (NALCN) than to the α1 subunit of voltage-gated Ca2+ channels (VGCCs). 29042437 2 79 theme leak 402:405 arg1 channel 407:413 Na+ leak channel non-selective 398:427 Na+ leak channel non-selective (NALCN) 398:435 The amino acid sequence and voltage insensitivity of Cch1 are more similar to those of Na+ leak channel non-selective (NALCN) than to the α1 subunit of voltage-gated Ca2+ channels (VGCCs). 29042437 1 80 theme channel 295:301 arg1 family 303:308 the eukaryotic pore-forming, four-domain cation channel family 247:308 the eukaryotic pore-forming, four-domain cation channel family 247:308 Saccharomyces cerevisiae Mid1 is composed of 548 amino acids and a regulatory subunit of Cch1, a member of the eukaryotic pore-forming, four-domain cation channel family. 29042437 10 81 theme single 1377:1382 arg1 mutants 1384:1390 the sec71Δ and sec72Δ single mutants 1355:1390 mutants 1384:1390 In the sec71Δ and sec72Δ single mutants defective in the post-translational protein transport into the endoplasmic reticulum (ER), Mid1ΔN23 could not mediate Ca2+ influx and did not undergo N-glycosylation, whereas wild-type Mid1 exhibited normal Ca2+ influx activity and N-glycosylation in these mutants. 29042437 0 82 theme yeast 64:68 arg1 subunit 86:92 the yeast regulatory Mid1 subunit 60:92 the yeast regulatory Mid1 subunit of the Cch1/VGCC/NALCN cation channel family 60:137 Post-translational processing and membrane translocation of the yeast regulatory Mid1 subunit of the Cch1/VGCC/NALCN cation channel family. 29042437 8 83 theme truncation 1110:1119 arg1 analysis 1121:1128 an N-terminal truncation analysis 1096:1128 an N-terminal truncation analysis 1096:1128 Moreover, an N-terminal truncation analysis revealed that even truncated Mid1 lacking 209 N-terminal amino acid residues was N-glycosylated and maintained Ca2+ influx activity. 29042437 11 84 theme protein 1786:1792 arg1 translocation 1794:1806 the post-translational protein translocation 1763:1806 the post-translational protein translocation 1763:1806 Therefore, the signal peptide-lacking Mid1ΔN23 protein may be translocated to the ER exclusively through the post-translational protein translocation, which typically requires an N-terminal signal peptide. 29042437 12 85 theme translocation 1923:1935 arg1 mechanisms 1901:1910 mechanisms 1901:1910 mechanisms of protein translocation 1901:1935 Mid1 may provide a tool for studying mechanisms of protein translocation into the ER. 29042437 3 86 theme NALCN-associated 620:635 arg1 proteins 637:644 NALCN-associated proteins 620:644 NALCN-associated proteins 620:644 Despite a lack in overall primary sequence similarity, Mid1 resembles in some aspects VGCC α2/δ regulatory subunits and NALCN-associated proteins. 29042437 4 87 theme subunit 762:768 arg1 function 733:740 the function 729:740 the function of the pore-forming subunit 729:768 Unlike animal α2/δ subunits, Mid1 and NALCN-associated proteins are essential for the function of the pore-forming subunit. 29042437 2 88 theme acid 321:324 arg1 sequence 326:333 The amino acid sequence 311:333 The amino acid sequence 311:333 The amino acid sequence and voltage insensitivity of Cch1 are more similar to those of Na+ leak channel non-selective (NALCN) than to the α1 subunit of voltage-gated Ca2+ channels (VGCCs). 29042437 2 88 theme acid 321:324 arg1 similar 378:384 similar 378:384 similar 378:384 The amino acid sequence and voltage insensitivity of Cch1 are more similar to those of Na+ leak channel non-selective (NALCN) than to the α1 subunit of voltage-gated Ca2+ channels (VGCCs). 29042437 11 89 theme Mid1ΔN23 1696:1703 arg1 protein 1705:1711 the signal peptide-lacking Mid1ΔN23 protein 1669:1711 the signal peptide-lacking Mid1ΔN23 protein 1669:1711 Therefore, the signal peptide-lacking Mid1ΔN23 protein may be translocated to the ER exclusively through the post-translational protein translocation, which typically requires an N-terminal signal peptide. 29042437 10 90 theme defective 1392:1400 arg1 sec71Δ 1359:1364 the sec71Δ and sec72Δ single mutants 1355:1390 sec71Δ 1359:1364 In the sec71Δ and sec72Δ single mutants defective in the post-translational protein transport into the endoplasmic reticulum (ER), Mid1ΔN23 could not mediate Ca2+ influx and did not undergo N-glycosylation, whereas wild-type Mid1 exhibited normal Ca2+ influx activity and N-glycosylation in these mutants. 29042437 2 91 theme Cch1 364:367 arg1 sequence 326:333 The amino acid sequence 311:333 The amino acid sequence 311:333 The amino acid sequence and voltage insensitivity of Cch1 are more similar to those of Na+ leak channel non-selective (NALCN) than to the α1 subunit of voltage-gated Ca2+ channels (VGCCs). 29042437 2 91 theme Cch1 364:367 arg1 insensitivity 347:359 voltage insensitivity 339:359 voltage insensitivity of Cch1 339:367 The amino acid sequence and voltage insensitivity of Cch1 are more similar to those of Na+ leak channel non-selective (NALCN) than to the α1 subunit of voltage-gated Ca2+ channels (VGCCs). 29042437 2 91 theme Cch1 364:367 arg1 similar 378:384 similar 378:384 similar 378:384 The amino acid sequence and voltage insensitivity of Cch1 are more similar to those of Na+ leak channel non-selective (NALCN) than to the α1 subunit of voltage-gated Ca2+ channels (VGCCs). 27655845 8 0 theme glycoproteome 1455:1467 arg1 analysis 1334:1341 a global analysis 1325:1341 a global analysis of O-GlcNAc dynamics during T cell activation 1325:1387 Overall, our studies provide a global analysis of O-GlcNAc dynamics during T cell activation and the first characterization, to our knowledge, of the O-GlcNAc glycoproteome in human T cells. 27655845 8 0 theme glycoproteome 1455:1467 arg1 characterization 1403:1418 the first characterization 1393:1418 the first characterization 1393:1418 Overall, our studies provide a global analysis of O-GlcNAc dynamics during T cell activation and the first characterization, to our knowledge, of the O-GlcNAc glycoproteome in human T cells. 27655845 7 1 theme proteins 1106:1113 arg1 Many 1083:1086 Many 1083:1086 Many 1083:1086 Many of the identified proteins had a functional relationship to RNA metabolism, and consistent with a connection between O-GlcNAc and RNA, inhibition of OGT impaired nascent RNA synthesis upon T cell activation. 27655845 7 1 theme proteins 1106:1113 arg1 proteins 1106:1113 the identified proteins 1091:1113 the identified proteins 1091:1113 Many of the identified proteins had a functional relationship to RNA metabolism, and consistent with a connection between O-GlcNAc and RNA, inhibition of OGT impaired nascent RNA synthesis upon T cell activation. 27655845 1 2 theme protein 130:136 arg1 modifications 156:168 protein posttranslational modifications 130:168 protein posttranslational modifications 130:168 T cell activation in response to Ag is largely regulated by protein posttranslational modifications. 27655845 5 3 theme immunological 953:965 arg1 synapse 967:973 the immunological synapse 949:973 the immunological synapse of murine T cells 949:991 T cell activation also led to changes in the relative expression of O-GlcNAc transferase (OGT) isoforms and accumulation of OGT at the immunological synapse of murine T cells. 27655845 5 4 theme isoforms 913:920 arg1 expression 872:881 the relative expression 859:881 the relative expression of O-GlcNAc transferase (OGT) isoforms 859:920 T cell activation also led to changes in the relative expression of O-GlcNAc transferase (OGT) isoforms and accumulation of OGT at the immunological synapse of murine T cells. 27655845 5 4 theme isoforms 913:920 arg1 accumulation 926:937 accumulation 926:937 accumulation of OGT at the immunological synapse of murine T cells 926:991 T cell activation also led to changes in the relative expression of O-GlcNAc transferase (OGT) isoforms and accumulation of OGT at the immunological synapse of murine T cells. 27655845 0 5 from Analysis 7:14 arg1 Cells 63:67 Activated Human T Cells 45:67 Activated Human T Cells 45:67 Global Analysis of O-GlcNAc Glycoproteins in Activated Human T Cells. 27655845 3 6 theme T 531:531 arg1 activation 538:547 T cell activation 531:547 T cell activation 531:547 Given that O-GlcNAc appears to regulate cell signaling pathways and protein activity similarly to phosphorylation, we performed a comprehensive analysis of O-GlcNAc during T cell activation to address the functional importance of this modification and to identify the modified proteins. 27655845 7 7 contain had 1115:1117 arg1 Many 1083:1086 Many 1083:1086 Many 1083:1086 Many of the identified proteins had a functional relationship to RNA metabolism, and consistent with a connection between O-GlcNAc and RNA, inhibition of OGT impaired nascent RNA synthesis upon T cell activation. 27655845 7 7 contain had 1115:1117 arg1 proteins 1106:1113 the identified proteins 1091:1113 the identified proteins 1091:1113 Many of the identified proteins had a functional relationship to RNA metabolism, and consistent with a connection between O-GlcNAc and RNA, inhibition of OGT impaired nascent RNA synthesis upon T cell activation. 27655845 7 7 contain had 1115:1117 arg2 relationship 1132:1143 a functional relationship 1119:1143 a functional relationship to RNA metabolism 1119:1161 Many of the identified proteins had a functional relationship to RNA metabolism, and consistent with a connection between O-GlcNAc and RNA, inhibition of OGT impaired nascent RNA synthesis upon T cell activation. 27655845 8 8 from glycoproteome 1455:1467 arg1 cells 1480:1484 human T cells 1472:1484 human T cells 1472:1484 Overall, our studies provide a global analysis of O-GlcNAc dynamics during T cell activation and the first characterization, to our knowledge, of the O-GlcNAc glycoproteome in human T cells. 27655845 2 9 gly glycosylation 272:284 arg1 residues 306:313 serine/threonine residues 289:313 serine/threonine residues 289:313 Although phosphorylation has been extensively characterized in T cells, much less is known about the glycosylation of serine/threonine residues by O-linked N-acetylglucosamine (O-GlcNAc). 27655845 8 10 theme human 1472:1476 arg1 cells 1480:1484 human T cells 1472:1484 human T cells 1472:1484 Overall, our studies provide a global analysis of O-GlcNAc dynamics during T cell activation and the first characterization, to our knowledge, of the O-GlcNAc glycoproteome in human T cells. 27655845 3 11 theme cell 399:402 arg1 pathways 414:421 cell signaling pathways 399:421 cell signaling pathways 399:421 Given that O-GlcNAc appears to regulate cell signaling pathways and protein activity similarly to phosphorylation, we performed a comprehensive analysis of O-GlcNAc during T cell activation to address the functional importance of this modification and to identify the modified proteins. 27655845 4 12 theme IL-2 766:769 arg1 production 771:780 IL-2 production 766:780 IL-2 production 766:780 Activation of T cells through the TCR resulted in a global elevation of O-GlcNAc levels and in the absence of O-GlcNAc, IL-2 production and proliferation were compromised. 27655845 5 13 from synapse 967:973 arg1 changes 848:854 changes 848:854 changes in the relative expression of O-GlcNAc transferase (OGT) isoforms and accumulation of OGT at the immunological synapse of murine T cells 848:991 T cell activation also led to changes in the relative expression of O-GlcNAc transferase (OGT) isoforms and accumulation of OGT at the immunological synapse of murine T cells. 27655845 5 13 from synapse 967:973 arg1 expression 872:881 the relative expression 859:881 the relative expression of O-GlcNAc transferase (OGT) isoforms 859:920 T cell activation also led to changes in the relative expression of O-GlcNAc transferase (OGT) isoforms and accumulation of OGT at the immunological synapse of murine T cells. 27655845 5 13 from synapse 967:973 arg1 accumulation 926:937 accumulation 926:937 accumulation of OGT at the immunological synapse of murine T cells 926:991 T cell activation also led to changes in the relative expression of O-GlcNAc transferase (OGT) isoforms and accumulation of OGT at the immunological synapse of murine T cells. 27655845 1 14 theme posttranslational 138:154 arg1 modifications 156:168 protein posttranslational modifications 130:168 protein posttranslational modifications 130:168 T cell activation in response to Ag is largely regulated by protein posttranslational modifications. 27655845 2 15 theme O-linked 318:325 arg1 O-GlcNAc 348:355 O-GlcNAc 348:355 O-GlcNAc 348:355 Although phosphorylation has been extensively characterized in T cells, much less is known about the glycosylation of serine/threonine residues by O-linked N-acetylglucosamine (O-GlcNAc). 27655845 2 15 theme O-linked 318:325 arg1 N-acetylglucosamine 327:345 O-linked N-acetylglucosamine 318:345 O-linked N-acetylglucosamine (O-GlcNAc) 318:356 Although phosphorylation has been extensively characterized in T cells, much less is known about the glycosylation of serine/threonine residues by O-linked N-acetylglucosamine (O-GlcNAc). 27655845 5 16 theme cell 820:823 arg1 activation 825:834 T cell activation 818:834 T cell activation 818:834 T cell activation also led to changes in the relative expression of O-GlcNAc transferase (OGT) isoforms and accumulation of OGT at the immunological synapse of murine T cells. 27655845 7 17 theme identified 1095:1104 arg1 proteins 1106:1113 the identified proteins 1091:1113 the identified proteins 1091:1113 Many of the identified proteins had a functional relationship to RNA metabolism, and consistent with a connection between O-GlcNAc and RNA, inhibition of OGT impaired nascent RNA synthesis upon T cell activation. 27655845 3 18 theme functional 564:573 arg1 importance 575:584 the functional importance 560:584 the functional importance of this modification 560:605 Given that O-GlcNAc appears to regulate cell signaling pathways and protein activity similarly to phosphorylation, we performed a comprehensive analysis of O-GlcNAc during T cell activation to address the functional importance of this modification and to identify the modified proteins. 27655845 7 19 theme cell 1279:1282 arg1 activation 1284:1293 T cell activation 1277:1293 T cell activation 1277:1293 Many of the identified proteins had a functional relationship to RNA metabolism, and consistent with a connection between O-GlcNAc and RNA, inhibition of OGT impaired nascent RNA synthesis upon T cell activation. 27655845 4 20 dep O-GlcNAc 756:763 arg1 the 741:743 the 741:743 the 741:743 Activation of T cells through the TCR resulted in a global elevation of O-GlcNAc levels and in the absence of O-GlcNAc, IL-2 production and proliferation were compromised. 27655845 4 20 dep O-GlcNAc 756:763 arg1 absence 745:751 absence 745:751 absence 745:751 Activation of T cells through the TCR resulted in a global elevation of O-GlcNAc levels and in the absence of O-GlcNAc, IL-2 production and proliferation were compromised. 27655845 8 21 theme global 1327:1332 arg1 analysis 1334:1341 a global analysis 1325:1341 a global analysis of O-GlcNAc dynamics during T cell activation 1325:1387 Overall, our studies provide a global analysis of O-GlcNAc dynamics during T cell activation and the first characterization, to our knowledge, of the O-GlcNAc glycoproteome in human T cells. 27655845 6 22 theme T 1074:1074 arg1 cells 1076:1080 human T cells 1068:1080 human T cells 1068:1080 Using a glycoproteomics approach, we identified >200 O-GlcNAc proteins in human T cells. 27655845 7 23 theme functional 1121:1130 arg1 relationship 1132:1143 a functional relationship 1119:1143 a functional relationship to RNA metabolism 1119:1161 Many of the identified proteins had a functional relationship to RNA metabolism, and consistent with a connection between O-GlcNAc and RNA, inhibition of OGT impaired nascent RNA synthesis upon T cell activation. 27655845 1 24 theme T 70:70 arg1 activation 77:86 T cell activation 70:86 T cell activation in response to Ag 70:104 T cell activation in response to Ag is largely regulated by protein posttranslational modifications. 27655845 8 25 theme T 1371:1371 arg1 activation 1378:1387 T cell activation 1371:1387 T cell activation 1371:1387 Overall, our studies provide a global analysis of O-GlcNAc dynamics during T cell activation and the first characterization, to our knowledge, of the O-GlcNAc glycoproteome in human T cells. 27655845 5 26 theme relative 863:870 arg1 expression 872:881 the relative expression 859:881 the relative expression of O-GlcNAc transferase (OGT) isoforms 859:920 T cell activation also led to changes in the relative expression of O-GlcNAc transferase (OGT) isoforms and accumulation of OGT at the immunological synapse of murine T cells. 27655845 5 27 theme T 818:818 arg1 activation 825:834 T cell activation 818:834 T cell activation 818:834 T cell activation also led to changes in the relative expression of O-GlcNAc transferase (OGT) isoforms and accumulation of OGT at the immunological synapse of murine T cells. 27655845 1 28 theme cell 72:75 arg1 activation 77:86 T cell activation 70:86 T cell activation in response to Ag 70:104 T cell activation in response to Ag is largely regulated by protein posttranslational modifications. 27655845 7 29 theme nascent 1250:1256 arg1 synthesis 1262:1270 nascent RNA synthesis 1250:1270 nascent RNA synthesis 1250:1270 Many of the identified proteins had a functional relationship to RNA metabolism, and consistent with a connection between O-GlcNAc and RNA, inhibition of OGT impaired nascent RNA synthesis upon T cell activation. 27655845 0 30 theme Global 0:5 arg1 Analysis 7:14 Global Analysis 0:14 Global Analysis of O-GlcNAc Glycoproteins in Activated Human T Cells. 0:68 Global Analysis of O-GlcNAc Glycoproteins in Activated Human T Cells. 27655845 3 31 theme modification 594:605 arg1 importance 575:584 the functional importance 560:584 the functional importance of this modification 560:605 Given that O-GlcNAc appears to regulate cell signaling pathways and protein activity similarly to phosphorylation, we performed a comprehensive analysis of O-GlcNAc during T cell activation to address the functional importance of this modification and to identify the modified proteins. 27655845 8 32 from characterization 1403:1418 arg1 cells 1480:1484 human T cells 1472:1484 human T cells 1472:1484 Overall, our studies provide a global analysis of O-GlcNAc dynamics during T cell activation and the first characterization, to our knowledge, of the O-GlcNAc glycoproteome in human T cells. 27655845 0 33 theme O-GlcNAc 19:26 arg1 Glycoproteins 28:40 O-GlcNAc Glycoproteins 19:40 O-GlcNAc Glycoproteins 19:40 Global Analysis of O-GlcNAc Glycoproteins in Activated Human T Cells. 27655845 3 34 dep performed 477:485 arg1 identify 614:621 identify 614:621 to identify the modified proteins 611:643 Given that O-GlcNAc appears to regulate cell signaling pathways and protein activity similarly to phosphorylation, we performed a comprehensive analysis of O-GlcNAc during T cell activation to address the functional importance of this modification and to identify the modified proteins. 27655845 3 34 dep performed 477:485 arg1 address 552:558 address 552:558 to address the functional importance of this modification 549:605 Given that O-GlcNAc appears to regulate cell signaling pathways and protein activity similarly to phosphorylation, we performed a comprehensive analysis of O-GlcNAc during T cell activation to address the functional importance of this modification and to identify the modified proteins. 27655845 2 35 theme residues 306:313 arg1 glycosylation 272:284 the glycosylation 268:284 the glycosylation of serine/threonine residues by O-linked N-acetylglucosamine (O-GlcNAc) 268:356 Although phosphorylation has been extensively characterized in T cells, much less is known about the glycosylation of serine/threonine residues by O-linked N-acetylglucosamine (O-GlcNAc). 27655845 6 36 theme human 1068:1072 arg1 cells 1076:1080 human T cells 1068:1080 human T cells 1068:1080 Using a glycoproteomics approach, we identified >200 O-GlcNAc proteins in human T cells. 27655845 4 37 theme T 660:660 arg1 cells 662:666 T cells 660:666 T cells 660:666 Activation of T cells through the TCR resulted in a global elevation of O-GlcNAc levels and in the absence of O-GlcNAc, IL-2 production and proliferation were compromised. 27655845 5 38 theme OGT 942:944 arg1 expression 872:881 the relative expression 859:881 the relative expression of O-GlcNAc transferase (OGT) isoforms 859:920 T cell activation also led to changes in the relative expression of O-GlcNAc transferase (OGT) isoforms and accumulation of OGT at the immunological synapse of murine T cells. 27655845 5 38 theme OGT 942:944 arg1 accumulation 926:937 accumulation 926:937 accumulation of OGT at the immunological synapse of murine T cells 926:991 T cell activation also led to changes in the relative expression of O-GlcNAc transferase (OGT) isoforms and accumulation of OGT at the immunological synapse of murine T cells. 27655845 2 39 theme serine/threonine 289:304 arg1 residues 306:313 serine/threonine residues 289:313 serine/threonine residues 289:313 Although phosphorylation has been extensively characterized in T cells, much less is known about the glycosylation of serine/threonine residues by O-linked N-acetylglucosamine (O-GlcNAc). 27655845 4 40 theme global 698:703 arg1 elevation 705:713 a global elevation 696:713 a global elevation of O-GlcNAc levels 696:732 Activation of T cells through the TCR resulted in a global elevation of O-GlcNAc levels and in the absence of O-GlcNAc, IL-2 production and proliferation were compromised. 27655845 4 41 theme O-GlcNAc 718:725 arg1 levels 727:732 O-GlcNAc levels 718:732 O-GlcNAc levels 718:732 Activation of T cells through the TCR resulted in a global elevation of O-GlcNAc levels and in the absence of O-GlcNAc, IL-2 production and proliferation were compromised. 27655845 8 42 from analysis 1334:1341 arg1 cells 1480:1484 human T cells 1472:1484 human T cells 1472:1484 Overall, our studies provide a global analysis of O-GlcNAc dynamics during T cell activation and the first characterization, to our knowledge, of the O-GlcNAc glycoproteome in human T cells. 27655845 7 43 with consistent 1168:1177 arg1 connection 1186:1195 a connection 1184:1195 a connection between O-GlcNAc and RNA 1184:1220 Many of the identified proteins had a functional relationship to RNA metabolism, and consistent with a connection between O-GlcNAc and RNA, inhibition of OGT impaired nascent RNA synthesis upon T cell activation. 27655845 0 44 theme Glycoproteins 28:40 arg1 Analysis 7:14 Global Analysis 0:14 Global Analysis of O-GlcNAc Glycoproteins in Activated Human T Cells. 0:68 Global Analysis of O-GlcNAc Glycoproteins in Activated Human T Cells. 27655845 3 45 theme protein 427:433 arg1 activity 435:442 protein activity 427:442 protein activity 427:442 Given that O-GlcNAc appears to regulate cell signaling pathways and protein activity similarly to phosphorylation, we performed a comprehensive analysis of O-GlcNAc during T cell activation to address the functional importance of this modification and to identify the modified proteins. 27655845 7 46 theme RNA 1148:1150 arg1 metabolism 1152:1161 RNA metabolism 1148:1161 RNA metabolism 1148:1161 Many of the identified proteins had a functional relationship to RNA metabolism, and consistent with a connection between O-GlcNAc and RNA, inhibition of OGT impaired nascent RNA synthesis upon T cell activation. 27655845 5 47 from changes 848:854 arg1 synapse 967:973 the immunological synapse 949:973 the immunological synapse of murine T cells 949:991 T cell activation also led to changes in the relative expression of O-GlcNAc transferase (OGT) isoforms and accumulation of OGT at the immunological synapse of murine T cells. 27655845 5 47 from changes 848:854 arg1 expression 872:881 the relative expression 859:881 the relative expression of O-GlcNAc transferase (OGT) isoforms 859:920 T cell activation also led to changes in the relative expression of O-GlcNAc transferase (OGT) isoforms and accumulation of OGT at the immunological synapse of murine T cells. 27655845 5 47 from changes 848:854 arg1 accumulation 926:937 accumulation 926:937 accumulation of OGT at the immunological synapse of murine T cells 926:991 T cell activation also led to changes in the relative expression of O-GlcNAc transferase (OGT) isoforms and accumulation of OGT at the immunological synapse of murine T cells. 27655845 4 48 theme cells 662:666 arg1 Activation 646:655 Activation 646:655 Activation of T cells through the TCR 646:682 Activation of T cells through the TCR resulted in a global elevation of O-GlcNAc levels and in the absence of O-GlcNAc, IL-2 production and proliferation were compromised. 27655845 3 49 theme signaling 404:412 arg1 pathways 414:421 cell signaling pathways 399:421 cell signaling pathways 399:421 Given that O-GlcNAc appears to regulate cell signaling pathways and protein activity similarly to phosphorylation, we performed a comprehensive analysis of O-GlcNAc during T cell activation to address the functional importance of this modification and to identify the modified proteins. 27655845 5 50 theme O-GlcNAc 886:893 arg1 OGT 908:910 OGT 908:910 OGT 908:910 T cell activation also led to changes in the relative expression of O-GlcNAc transferase (OGT) isoforms and accumulation of OGT at the immunological synapse of murine T cells. 27655845 5 50 theme O-GlcNAc 886:893 arg1 transferase 895:905 O-GlcNAc transferase 886:905 O-GlcNAc transferase (OGT) isoforms 886:920 T cell activation also led to changes in the relative expression of O-GlcNAc transferase (OGT) isoforms and accumulation of OGT at the immunological synapse of murine T cells. 27655845 0 51 theme T 61:61 arg1 Cells 63:67 Activated Human T Cells 45:67 Activated Human T Cells 45:67 Global Analysis of O-GlcNAc Glycoproteins in Activated Human T Cells. 27655845 2 52 theme T 234:234 arg1 cells 236:240 T cells 234:240 T cells 234:240 Although phosphorylation has been extensively characterized in T cells, much less is known about the glycosylation of serine/threonine residues by O-linked N-acetylglucosamine (O-GlcNAc). 27655845 4 53 theme levels 727:732 arg1 elevation 705:713 a global elevation 696:713 a global elevation of O-GlcNAc levels 696:732 Activation of T cells through the TCR resulted in a global elevation of O-GlcNAc levels and in the absence of O-GlcNAc, IL-2 production and proliferation were compromised. 27655845 0 54 theme Activated 45:53 arg1 Cells 63:67 Activated Human T Cells 45:67 Activated Human T Cells 45:67 Global Analysis of O-GlcNAc Glycoproteins in Activated Human T Cells. 27655845 2 55 link O-linked 318:325 arg1 O-GlcNAc 348:355 O-GlcNAc 348:355 O-GlcNAc 348:355 Although phosphorylation has been extensively characterized in T cells, much less is known about the glycosylation of serine/threonine residues by O-linked N-acetylglucosamine (O-GlcNAc). 27655845 2 55 link O-linked 318:325 arg1 N-acetylglucosamine 327:345 O-linked N-acetylglucosamine 318:345 O-linked N-acetylglucosamine (O-GlcNAc) 318:356 Although phosphorylation has been extensively characterized in T cells, much less is known about the glycosylation of serine/threonine residues by O-linked N-acetylglucosamine (O-GlcNAc). 27655845 8 56 theme cell 1373:1376 arg1 activation 1378:1387 T cell activation 1371:1387 T cell activation 1371:1387 Overall, our studies provide a global analysis of O-GlcNAc dynamics during T cell activation and the first characterization, to our knowledge, of the O-GlcNAc glycoproteome in human T cells. 27655845 7 57 theme RNA 1258:1260 arg1 synthesis 1262:1270 nascent RNA synthesis 1250:1270 nascent RNA synthesis 1250:1270 Many of the identified proteins had a functional relationship to RNA metabolism, and consistent with a connection between O-GlcNAc and RNA, inhibition of OGT impaired nascent RNA synthesis upon T cell activation. 27655845 3 58 theme O-GlcNAc 515:522 arg1 analysis 503:510 a comprehensive analysis 487:510 a comprehensive analysis of O-GlcNAc 487:522 Given that O-GlcNAc appears to regulate cell signaling pathways and protein activity similarly to phosphorylation, we performed a comprehensive analysis of O-GlcNAc during T cell activation to address the functional importance of this modification and to identify the modified proteins. 27655845 5 59 theme T 985:985 arg1 cells 987:991 murine T cells 978:991 murine T cells 978:991 T cell activation also led to changes in the relative expression of O-GlcNAc transferase (OGT) isoforms and accumulation of OGT at the immunological synapse of murine T cells. 27655845 8 60 theme O-GlcNAc 1346:1353 arg1 dynamics 1355:1362 O-GlcNAc dynamics 1346:1362 O-GlcNAc dynamics 1346:1362 Overall, our studies provide a global analysis of O-GlcNAc dynamics during T cell activation and the first characterization, to our knowledge, of the O-GlcNAc glycoproteome in human T cells. 27655845 3 61 theme comprehensive 489:501 arg1 analysis 503:510 a comprehensive analysis 487:510 a comprehensive analysis of O-GlcNAc 487:522 Given that O-GlcNAc appears to regulate cell signaling pathways and protein activity similarly to phosphorylation, we performed a comprehensive analysis of O-GlcNAc during T cell activation to address the functional importance of this modification and to identify the modified proteins. 27655845 8 62 theme dynamics 1355:1362 arg1 analysis 1334:1341 a global analysis 1325:1341 a global analysis of O-GlcNAc dynamics during T cell activation 1325:1387 Overall, our studies provide a global analysis of O-GlcNAc dynamics during T cell activation and the first characterization, to our knowledge, of the O-GlcNAc glycoproteome in human T cells. 27655845 8 62 theme dynamics 1355:1362 arg1 characterization 1403:1418 the first characterization 1393:1418 the first characterization 1393:1418 Overall, our studies provide a global analysis of O-GlcNAc dynamics during T cell activation and the first characterization, to our knowledge, of the O-GlcNAc glycoproteome in human T cells. 27655845 5 63 theme murine 978:983 arg1 cells 987:991 murine T cells 978:991 murine T cells 978:991 T cell activation also led to changes in the relative expression of O-GlcNAc transferase (OGT) isoforms and accumulation of OGT at the immunological synapse of murine T cells. 27655845 8 64 theme O-GlcNAc 1446:1453 arg1 glycoproteome 1455:1467 the O-GlcNAc glycoproteome 1442:1467 the O-GlcNAc glycoproteome in human T cells 1442:1484 Overall, our studies provide a global analysis of O-GlcNAc dynamics during T cell activation and the first characterization, to our knowledge, of the O-GlcNAc glycoproteome in human T cells. 27655845 5 65 theme cells 987:991 arg1 synapse 967:973 the immunological synapse 949:973 the immunological synapse of murine T cells 949:991 T cell activation also led to changes in the relative expression of O-GlcNAc transferase (OGT) isoforms and accumulation of OGT at the immunological synapse of murine T cells. 27655845 7 66 theme OGT 1237:1239 arg1 inhibition 1223:1232 inhibition 1223:1232 inhibition of OGT 1223:1239 Many of the identified proteins had a functional relationship to RNA metabolism, and consistent with a connection between O-GlcNAc and RNA, inhibition of OGT impaired nascent RNA synthesis upon T cell activation. 27655845 8 67 theme T 1478:1478 arg1 cells 1480:1484 human T cells 1472:1484 human T cells 1472:1484 Overall, our studies provide a global analysis of O-GlcNAc dynamics during T cell activation and the first characterization, to our knowledge, of the O-GlcNAc glycoproteome in human T cells. 27655845 7 68 theme T 1277:1277 arg1 activation 1284:1293 T cell activation 1277:1293 T cell activation 1277:1293 Many of the identified proteins had a functional relationship to RNA metabolism, and consistent with a connection between O-GlcNAc and RNA, inhibition of OGT impaired nascent RNA synthesis upon T cell activation. 27655845 3 69 theme modified 627:634 arg1 proteins 636:643 the modified proteins 623:643 the modified proteins 623:643 Given that O-GlcNAc appears to regulate cell signaling pathways and protein activity similarly to phosphorylation, we performed a comprehensive analysis of O-GlcNAc during T cell activation to address the functional importance of this modification and to identify the modified proteins. 27655845 6 70 theme O-GlcNAc 1047:1054 arg1 proteins 1056:1063 >200 O-GlcNAc proteins 1042:1063 >200 O-GlcNAc proteins 1042:1063 Using a glycoproteomics approach, we identified >200 O-GlcNAc proteins in human T cells. 27655845 3 71 theme cell 533:536 arg1 activation 538:547 T cell activation 531:547 T cell activation 531:547 Given that O-GlcNAc appears to regulate cell signaling pathways and protein activity similarly to phosphorylation, we performed a comprehensive analysis of O-GlcNAc during T cell activation to address the functional importance of this modification and to identify the modified proteins. 27655845 1 72 from activation 77:86 arg1 response 91:98 response 91:98 response to Ag 91:104 T cell activation in response to Ag is largely regulated by protein posttranslational modifications. 27655845 6 73 theme glycoproteomics 1002:1016 arg1 approach 1018:1025 a glycoproteomics approach 1000:1025 a glycoproteomics approach 1000:1025 Using a glycoproteomics approach, we identified >200 O-GlcNAc proteins in human T cells. 27655845 0 74 theme Human 55:59 arg1 Cells 63:67 Activated Human T Cells 45:67 Activated Human T Cells 45:67 Global Analysis of O-GlcNAc Glycoproteins in Activated Human T Cells. 27655845 8 75 theme first 1397:1401 arg1 characterization 1403:1418 the first characterization 1393:1418 the first characterization 1393:1418 Overall, our studies provide a global analysis of O-GlcNAc dynamics during T cell activation and the first characterization, to our knowledge, of the O-GlcNAc glycoproteome in human T cells. 27655845 5 76 theme transferase 895:905 arg1 isoforms 913:920 O-GlcNAc transferase (OGT) isoforms 886:920 O-GlcNAc transferase (OGT) isoforms 886:920 T cell activation also led to changes in the relative expression of O-GlcNAc transferase (OGT) isoforms and accumulation of OGT at the immunological synapse of murine T cells. 27655845 8 77 from cells 1480:1484 arg1 analysis 1334:1341 a global analysis 1325:1341 a global analysis of O-GlcNAc dynamics during T cell activation 1325:1387 Overall, our studies provide a global analysis of O-GlcNAc dynamics during T cell activation and the first characterization, to our knowledge, of the O-GlcNAc glycoproteome in human T cells. 27655845 8 77 from cells 1480:1484 arg1 characterization 1403:1418 the first characterization 1393:1418 the first characterization 1393:1418 Overall, our studies provide a global analysis of O-GlcNAc dynamics during T cell activation and the first characterization, to our knowledge, of the O-GlcNAc glycoproteome in human T cells. 24923446 9 0 theme inhibitors 1649:1658 arg1 development 1620:1630 the development 1616:1630 the development of anti-adhesive inhibitors that could deter the adherence of pathogenic oral streptococci and thereby prevent the onset of infections 1616:1765 This study concludes that identification of the metal ion and carbohydrate adherence motifs on both SRCRs and AgI/II homologs could lead to the development of anti-adhesive inhibitors that could deter the adherence of pathogenic oral streptococci and thereby prevent the onset of infections. 24923446 7 1 theme described 1140:1148 arg1 peptide 1157:1163 The previously described SRCRP2 peptide 1125:1163 The previously described SRCRP2 peptide that was shown to aggregate several oral streptococci 1125:1217 The previously described SRCRP2 peptide that was shown to aggregate several oral streptococci displayed limited aggregation and also nonspecific adherence compared to SRCR domains. 24923446 1 2 theme protein 275:281 arg1 antigen 283:289 the surface protein antigen I/II (AgI/II) 263:303 the surface protein antigen I/II (AgI/II) 263:303 Oral streptococci adhere to tooth-immobilized glycoprotein 340 (GP340) via the surface protein antigen I/II (AgI/II) and its homologs as the first step in pathogenesis. 24923446 9 3 theme infections 1756:1765 arg1 onset 1747:1751 the onset 1743:1751 the onset of infections 1743:1765 This study concludes that identification of the metal ion and carbohydrate adherence motifs on both SRCRs and AgI/II homologs could lead to the development of anti-adhesive inhibitors that could deter the adherence of pathogenic oral streptococci and thereby prevent the onset of infections. 24923446 9 4 theme metal 1524:1528 arg1 ion 1530:1532 metal ion 1524:1532 metal ion 1524:1532 This study concludes that identification of the metal ion and carbohydrate adherence motifs on both SRCRs and AgI/II homologs could lead to the development of anti-adhesive inhibitors that could deter the adherence of pathogenic oral streptococci and thereby prevent the onset of infections. 24923446 4 5 attach present 778:784 arg2 carbohydrates 764:776 the O-linked carbohydrates 751:776 the O-linked carbohydrates present on the SRCRs 751:797 This interaction is significantly dependent on the O-linked carbohydrates present on the SRCRs. 24923446 4 5 attach present 778:784 arg1 SRCRs 793:797 the SRCRs 789:797 the SRCRs 789:797 This interaction is significantly dependent on the O-linked carbohydrates present on the SRCRs. 24923446 6 6 from increase 1070:1077 arg1 aggregation 1112:1122 aggregation 1112:1122 aggregation 1112:1122 Compared with the single SRCR domain, the three tandem SRCR domains displayed a collective/cooperative increase in their bacterial adherence and aggregation. 24923446 6 6 from increase 1070:1077 arg1 adherence 1098:1106 their bacterial adherence 1082:1106 their bacterial adherence 1082:1106 Compared with the single SRCR domain, the three tandem SRCR domains displayed a collective/cooperative increase in their bacterial adherence and aggregation. 24923446 9 7 from SRCRs 1576:1580 arg1 identification 1502:1515 identification 1502:1515 identification of the metal ion and carbohydrate adherence motifs on both SRCRs and AgI/II homologs 1502:1600 This study concludes that identification of the metal ion and carbohydrate adherence motifs on both SRCRs and AgI/II homologs could lead to the development of anti-adhesive inhibitors that could deter the adherence of pathogenic oral streptococci and thereby prevent the onset of infections. 24923446 9 8 theme adherence 1551:1559 arg1 motifs 1561:1566 carbohydrate adherence motifs 1538:1566 carbohydrate adherence motifs 1538:1566 This study concludes that identification of the metal ion and carbohydrate adherence motifs on both SRCRs and AgI/II homologs could lead to the development of anti-adhesive inhibitors that could deter the adherence of pathogenic oral streptococci and thereby prevent the onset of infections. 24923446 0 9 theme high 134:137 arg1 interaction 148:158 the high affinity interaction 130:158 the high affinity interaction with antigen I/II homologs 130:185 The calcium-induced conformation and glycosylation of scavenger-rich cysteine repeat (SRCR) domains of glycoprotein 340 influence the high affinity interaction with antigen I/II homologs. 24923446 3 10 theme nanomolar 599:607 arg1 affinity 609:616 nanomolar affinity 599:616 nanomolar affinity 599:616 Our results also show that AgI/II adheres specifically with nanomolar affinity to the calcium-induced SRCR conformation in an immobilized state and not in solution. 24923446 1 11 theme glycoprotein 234:245 arg1 GP340 252:256 GP340 252:256 GP340 252:256 Oral streptococci adhere to tooth-immobilized glycoprotein 340 (GP340) via the surface protein antigen I/II (AgI/II) and its homologs as the first step in pathogenesis. 24923446 1 11 theme glycoprotein 234:245 arg1 340 247:249 tooth-immobilized glycoprotein 340 216:249 tooth-immobilized glycoprotein 340 (GP340) via the surface protein antigen I/II (AgI/II) and its homologs 216:320 Oral streptococci adhere to tooth-immobilized glycoprotein 340 (GP340) via the surface protein antigen I/II (AgI/II) and its homologs as the first step in pathogenesis. 24923446 8 12 theme species-specific 1332:1347 arg1 adherence/aggregation 1349:1369 distinct species-specific adherence/aggregation 1323:1369 distinct species-specific adherence/aggregation between Streptococcus mutans AgI/II and Streptococcus gordonii SspB in their interaction with the SRCRs 1323:1473 Finally, we show distinct species-specific adherence/aggregation between Streptococcus mutans AgI/II and Streptococcus gordonii SspB in their interaction with the SRCRs. 24923446 5 13 theme C-terminal 913:922 arg1 regions 924:930 the apical and C-terminal regions 898:930 the apical and C-terminal regions of AgI/II 898:940 This study also establishes that a single SRCR domain of GP340 contains the two surfaces to which the apical and C-terminal regions of AgI/II noncompetitively adhere. 24923446 0 14 theme antigen 165:171 arg1 homologs 178:185 antigen I/II homologs 165:185 antigen I/II homologs 165:185 The calcium-induced conformation and glycosylation of scavenger-rich cysteine repeat (SRCR) domains of glycoprotein 340 influence the high affinity interaction with antigen I/II homologs. 24923446 3 15 theme calcium-induced 625:639 arg1 conformation 646:657 the calcium-induced SRCR conformation 621:657 the calcium-induced SRCR conformation in an immobilized state and not in solution 621:701 Our results also show that AgI/II adheres specifically with nanomolar affinity to the calcium-induced SRCR conformation in an immobilized state and not in solution. 24923446 9 16 theme AgI/II 1586:1591 arg1 homologs 1593:1600 AgI/II homologs 1586:1600 AgI/II homologs 1586:1600 This study concludes that identification of the metal ion and carbohydrate adherence motifs on both SRCRs and AgI/II homologs could lead to the development of anti-adhesive inhibitors that could deter the adherence of pathogenic oral streptococci and thereby prevent the onset of infections. 24923446 6 17 theme SRCR 1022:1025 arg1 domains 1027:1033 the three tandem SRCR domains 1005:1033 the three tandem SRCR domains 1005:1033 Compared with the single SRCR domain, the three tandem SRCR domains displayed a collective/cooperative increase in their bacterial adherence and aggregation. 24923446 0 18 theme repeat 78:83 arg1 domains 92:98 scavenger-rich cysteine repeat (SRCR) domains 54:98 scavenger-rich cysteine repeat (SRCR) domains of glycoprotein 340 54:118 The calcium-induced conformation and glycosylation of scavenger-rich cysteine repeat (SRCR) domains of glycoprotein 340 influence the high affinity interaction with antigen I/II homologs. 24923446 0 18 theme repeat 78:83 arg1 340 116:118 glycoprotein 340 103:118 glycoprotein 340 103:118 The calcium-induced conformation and glycosylation of scavenger-rich cysteine repeat (SRCR) domains of glycoprotein 340 influence the high affinity interaction with antigen I/II homologs. 24923446 7 19 theme several 1193:1199 arg1 streptococci 1206:1217 aggregate several oral streptococci 1183:1217 aggregate several oral streptococci 1183:1217 The previously described SRCRP2 peptide that was shown to aggregate several oral streptococci displayed limited aggregation and also nonspecific adherence compared to SRCR domains. 24923446 3 20 from conformation 646:657 arg1 state 677:681 an immobilized state 662:681 an immobilized state 662:681 Our results also show that AgI/II adheres specifically with nanomolar affinity to the calcium-induced SRCR conformation in an immobilized state and not in solution. 24923446 3 20 from conformation 646:657 arg1 solution 694:701 solution 694:701 solution 694:701 Our results also show that AgI/II adheres specifically with nanomolar affinity to the calcium-induced SRCR conformation in an immobilized state and not in solution. 24923446 2 21 theme cysteine 497:504 arg1 repeat 506:511 scavenger-rich cysteine repeat 482:511 the scavenger-rich cysteine repeat (SRCRs) domains of GP340 478:536 Studying this interaction using recombinant proteins, we observed that calcium increases the conformational stability of the scavenger-rich cysteine repeat (SRCRs) domains of GP340. 24923446 2 21 theme cysteine 497:504 arg1 SRCRs 514:518 SRCRs 514:518 SRCRs 514:518 Studying this interaction using recombinant proteins, we observed that calcium increases the conformational stability of the scavenger-rich cysteine repeat (SRCRs) domains of GP340. 24923446 0 22 theme SRCR 86:89 arg1 domains 92:98 scavenger-rich cysteine repeat (SRCR) domains 54:98 scavenger-rich cysteine repeat (SRCR) domains of glycoprotein 340 54:118 The calcium-induced conformation and glycosylation of scavenger-rich cysteine repeat (SRCR) domains of glycoprotein 340 influence the high affinity interaction with antigen I/II homologs. 24923446 0 22 theme SRCR 86:89 arg1 340 116:118 glycoprotein 340 103:118 glycoprotein 340 103:118 The calcium-induced conformation and glycosylation of scavenger-rich cysteine repeat (SRCR) domains of glycoprotein 340 influence the high affinity interaction with antigen I/II homologs. 24923446 1 23 theme first 329:333 arg1 step 335:338 the first step 325:338 the first step in pathogenesis 325:354 Oral streptococci adhere to tooth-immobilized glycoprotein 340 (GP340) via the surface protein antigen I/II (AgI/II) and its homologs as the first step in pathogenesis. 24923446 5 24 theme apical 902:907 arg1 regions 924:930 the apical and C-terminal regions 898:930 the apical and C-terminal regions of AgI/II 898:940 This study also establishes that a single SRCR domain of GP340 contains the two surfaces to which the apical and C-terminal regions of AgI/II noncompetitively adhere. 24923446 0 25 with interaction 148:158 arg1 homologs 178:185 antigen I/II homologs 165:185 antigen I/II homologs 165:185 The calcium-induced conformation and glycosylation of scavenger-rich cysteine repeat (SRCR) domains of glycoprotein 340 influence the high affinity interaction with antigen I/II homologs. 24923446 8 26 with interaction 1448:1458 arg1 SRCRs 1469:1473 the SRCRs 1465:1473 the SRCRs 1465:1473 Finally, we show distinct species-specific adherence/aggregation between Streptococcus mutans AgI/II and Streptococcus gordonii SspB in their interaction with the SRCRs. 24923446 0 27 theme domains 92:98 arg1 conformation 20:31 calcium-induced conformation 4:31 calcium-induced conformation 4:31 The calcium-induced conformation and glycosylation of scavenger-rich cysteine repeat (SRCR) domains of glycoprotein 340 influence the high affinity interaction with antigen I/II homologs. 24923446 0 27 theme domains 92:98 arg1 glycosylation 37:49 glycosylation 37:49 glycosylation 37:49 The calcium-induced conformation and glycosylation of scavenger-rich cysteine repeat (SRCR) domains of glycoprotein 340 influence the high affinity interaction with antigen I/II homologs. 24923446 6 28 theme SRCR 992:995 arg1 domain 997:1002 the single SRCR domain 981:1002 the single SRCR domain 981:1002 Compared with the single SRCR domain, the three tandem SRCR domains displayed a collective/cooperative increase in their bacterial adherence and aggregation. 24923446 5 29 contain contains 863:870 arg2 surfaces 880:887 the two surfaces 872:887 the two surfaces to which the apical and C-terminal regions of AgI/II noncompetitively adhere 872:964 This study also establishes that a single SRCR domain of GP340 contains the two surfaces to which the apical and C-terminal regions of AgI/II noncompetitively adhere. 24923446 5 29 contain contains 863:870 arg1 GP340 857:861 GP340 857:861 GP340 857:861 This study also establishes that a single SRCR domain of GP340 contains the two surfaces to which the apical and C-terminal regions of AgI/II noncompetitively adhere. 24923446 5 29 contain contains 863:870 arg1 domain 847:852 a single SRCR domain 833:852 a single SRCR domain of GP340 833:861 This study also establishes that a single SRCR domain of GP340 contains the two surfaces to which the apical and C-terminal regions of AgI/II noncompetitively adhere. 24923446 2 30 theme recombinant 389:399 arg1 proteins 401:408 recombinant proteins 389:408 recombinant proteins 389:408 Studying this interaction using recombinant proteins, we observed that calcium increases the conformational stability of the scavenger-rich cysteine repeat (SRCRs) domains of GP340. 24923446 0 31 theme glycoprotein 103:114 arg1 340 116:118 glycoprotein 340 103:118 glycoprotein 340 103:118 The calcium-induced conformation and glycosylation of scavenger-rich cysteine repeat (SRCR) domains of glycoprotein 340 influence the high affinity interaction with antigen I/II homologs. 24923446 9 32 theme anti-adhesive 1635:1647 arg1 inhibitors 1649:1658 anti-adhesive inhibitors 1635:1658 anti-adhesive inhibitors that could deter the adherence of pathogenic oral streptococci and thereby prevent the onset of infections 1635:1765 This study concludes that identification of the metal ion and carbohydrate adherence motifs on both SRCRs and AgI/II homologs could lead to the development of anti-adhesive inhibitors that could deter the adherence of pathogenic oral streptococci and thereby prevent the onset of infections. 24923446 6 33 theme bacterial 1088:1096 arg1 adherence 1098:1106 their bacterial adherence 1082:1106 their bacterial adherence 1082:1106 Compared with the single SRCR domain, the three tandem SRCR domains displayed a collective/cooperative increase in their bacterial adherence and aggregation. 24923446 5 34 theme single 835:840 arg1 GP340 857:861 GP340 857:861 GP340 857:861 This study also establishes that a single SRCR domain of GP340 contains the two surfaces to which the apical and C-terminal regions of AgI/II noncompetitively adhere. 24923446 5 34 theme single 835:840 arg1 domain 847:852 a single SRCR domain 833:852 a single SRCR domain of GP340 833:861 This study also establishes that a single SRCR domain of GP340 contains the two surfaces to which the apical and C-terminal regions of AgI/II noncompetitively adhere. 24923446 6 35 theme collective/cooperative 1047:1068 arg1 increase 1070:1077 a collective/cooperative increase 1045:1077 a collective/cooperative increase in their bacterial adherence and aggregation 1045:1122 Compared with the single SRCR domain, the three tandem SRCR domains displayed a collective/cooperative increase in their bacterial adherence and aggregation. 24923446 9 36 dep ion 1530:1532 arg1 the 1520:1522 the 1520:1522 the 1520:1522 This study concludes that identification of the metal ion and carbohydrate adherence motifs on both SRCRs and AgI/II homologs could lead to the development of anti-adhesive inhibitors that could deter the adherence of pathogenic oral streptococci and thereby prevent the onset of infections. 24923446 1 37 from step 335:338 arg1 pathogenesis 343:354 pathogenesis 343:354 pathogenesis 343:354 Oral streptococci adhere to tooth-immobilized glycoprotein 340 (GP340) via the surface protein antigen I/II (AgI/II) and its homologs as the first step in pathogenesis. 24923446 9 38 from motifs 1561:1566 arg1 SRCRs 1576:1580 SRCRs 1576:1580 SRCRs 1576:1580 This study concludes that identification of the metal ion and carbohydrate adherence motifs on both SRCRs and AgI/II homologs could lead to the development of anti-adhesive inhibitors that could deter the adherence of pathogenic oral streptococci and thereby prevent the onset of infections. 24923446 9 38 from motifs 1561:1566 arg1 homologs 1593:1600 AgI/II homologs 1586:1600 AgI/II homologs 1586:1600 This study concludes that identification of the metal ion and carbohydrate adherence motifs on both SRCRs and AgI/II homologs could lead to the development of anti-adhesive inhibitors that could deter the adherence of pathogenic oral streptococci and thereby prevent the onset of infections. 24923446 0 39 theme scavenger-rich 54:67 arg1 domains 92:98 scavenger-rich cysteine repeat (SRCR) domains 54:98 scavenger-rich cysteine repeat (SRCR) domains of glycoprotein 340 54:118 The calcium-induced conformation and glycosylation of scavenger-rich cysteine repeat (SRCR) domains of glycoprotein 340 influence the high affinity interaction with antigen I/II homologs. 24923446 0 39 theme scavenger-rich 54:67 arg1 340 116:118 glycoprotein 340 103:118 glycoprotein 340 103:118 The calcium-induced conformation and glycosylation of scavenger-rich cysteine repeat (SRCR) domains of glycoprotein 340 influence the high affinity interaction with antigen I/II homologs. 24923446 9 40 theme pathogenic 1694:1703 arg1 streptococci 1710:1721 pathogenic oral streptococci 1694:1721 pathogenic oral streptococci 1694:1721 This study concludes that identification of the metal ion and carbohydrate adherence motifs on both SRCRs and AgI/II homologs could lead to the development of anti-adhesive inhibitors that could deter the adherence of pathogenic oral streptococci and thereby prevent the onset of infections. 24923446 9 41 theme streptococci 1710:1721 arg1 adherence 1681:1689 the adherence 1677:1689 the adherence of pathogenic oral streptococci 1677:1721 This study concludes that identification of the metal ion and carbohydrate adherence motifs on both SRCRs and AgI/II homologs could lead to the development of anti-adhesive inhibitors that could deter the adherence of pathogenic oral streptococci and thereby prevent the onset of infections. 24923446 9 42 from ion 1530:1532 arg1 SRCRs 1576:1580 SRCRs 1576:1580 SRCRs 1576:1580 This study concludes that identification of the metal ion and carbohydrate adherence motifs on both SRCRs and AgI/II homologs could lead to the development of anti-adhesive inhibitors that could deter the adherence of pathogenic oral streptococci and thereby prevent the onset of infections. 24923446 9 42 from ion 1530:1532 arg1 homologs 1593:1600 AgI/II homologs 1586:1600 AgI/II homologs 1586:1600 This study concludes that identification of the metal ion and carbohydrate adherence motifs on both SRCRs and AgI/II homologs could lead to the development of anti-adhesive inhibitors that could deter the adherence of pathogenic oral streptococci and thereby prevent the onset of infections. 24923446 4 43 link O-linked 755:762 arg1 carbohydrates 764:776 the O-linked carbohydrates 751:776 the O-linked carbohydrates present on the SRCRs 751:797 This interaction is significantly dependent on the O-linked carbohydrates present on the SRCRs. 24923446 7 44 theme SRCRP2 1150:1155 arg1 peptide 1157:1163 The previously described SRCRP2 peptide 1125:1163 The previously described SRCRP2 peptide that was shown to aggregate several oral streptococci 1125:1217 The previously described SRCRP2 peptide that was shown to aggregate several oral streptococci displayed limited aggregation and also nonspecific adherence compared to SRCR domains. 24923446 7 45 theme SRCR 1292:1295 arg1 domains 1297:1303 SRCR domains 1292:1303 SRCR domains 1292:1303 The previously described SRCRP2 peptide that was shown to aggregate several oral streptococci displayed limited aggregation and also nonspecific adherence compared to SRCR domains. 24923446 1 46 theme surface 267:273 arg1 antigen 283:289 the surface protein antigen I/II (AgI/II) 263:303 the surface protein antigen I/II (AgI/II) 263:303 Oral streptococci adhere to tooth-immobilized glycoprotein 340 (GP340) via the surface protein antigen I/II (AgI/II) and its homologs as the first step in pathogenesis. 24923446 9 47 from homologs 1593:1600 arg1 identification 1502:1515 identification 1502:1515 identification of the metal ion and carbohydrate adherence motifs on both SRCRs and AgI/II homologs 1502:1600 This study concludes that identification of the metal ion and carbohydrate adherence motifs on both SRCRs and AgI/II homologs could lead to the development of anti-adhesive inhibitors that could deter the adherence of pathogenic oral streptococci and thereby prevent the onset of infections. 24923446 1 48 theme Oral 188:191 arg1 streptococci 193:204 Oral streptococci 188:204 Oral streptococci 188:204 Oral streptococci adhere to tooth-immobilized glycoprotein 340 (GP340) via the surface protein antigen I/II (AgI/II) and its homologs as the first step in pathogenesis. 24923446 7 49 theme nonspecific 1258:1268 arg1 adherence 1270:1278 nonspecific adherence 1258:1278 nonspecific adherence 1258:1278 The previously described SRCRP2 peptide that was shown to aggregate several oral streptococci displayed limited aggregation and also nonspecific adherence compared to SRCR domains. 24923446 1 50 gly glycoprotein 234:245 arg1 glycoprotein 234:245 tooth-immobilized glycoprotein 340 216:249 tooth-immobilized glycoprotein 340 (GP340) via the surface protein antigen I/II (AgI/II) and its homologs 216:320 Oral streptococci adhere to tooth-immobilized glycoprotein 340 (GP340) via the surface protein antigen I/II (AgI/II) and its homologs as the first step in pathogenesis. 24923446 9 51 theme ion 1530:1532 arg1 identification 1502:1515 identification 1502:1515 identification of the metal ion and carbohydrate adherence motifs on both SRCRs and AgI/II homologs 1502:1600 This study concludes that identification of the metal ion and carbohydrate adherence motifs on both SRCRs and AgI/II homologs could lead to the development of anti-adhesive inhibitors that could deter the adherence of pathogenic oral streptococci and thereby prevent the onset of infections. 24923446 6 52 theme single 985:990 arg1 domain 997:1002 the single SRCR domain 981:1002 the single SRCR domain 981:1002 Compared with the single SRCR domain, the three tandem SRCR domains displayed a collective/cooperative increase in their bacterial adherence and aggregation. 24923446 8 53 dep Streptococcus 1379:1391 arg1 SspB 1434:1437 SspB 1434:1437 SspB 1434:1437 Finally, we show distinct species-specific adherence/aggregation between Streptococcus mutans AgI/II and Streptococcus gordonii SspB in their interaction with the SRCRs. 24923446 8 53 dep Streptococcus 1379:1391 arg1 AgI/II 1400:1405 Streptococcus mutans AgI/II 1379:1405 Streptococcus mutans AgI/II 1379:1405 Finally, we show distinct species-specific adherence/aggregation between Streptococcus mutans AgI/II and Streptococcus gordonii SspB in their interaction with the SRCRs. 24923446 9 54 theme carbohydrate 1538:1549 arg1 motifs 1561:1566 carbohydrate adherence motifs 1538:1566 carbohydrate adherence motifs 1538:1566 This study concludes that identification of the metal ion and carbohydrate adherence motifs on both SRCRs and AgI/II homologs could lead to the development of anti-adhesive inhibitors that could deter the adherence of pathogenic oral streptococci and thereby prevent the onset of infections. 24923446 0 55 theme affinity 139:146 arg1 interaction 148:158 the high affinity interaction 130:158 the high affinity interaction with antigen I/II homologs 130:185 The calcium-induced conformation and glycosylation of scavenger-rich cysteine repeat (SRCR) domains of glycoprotein 340 influence the high affinity interaction with antigen I/II homologs. 24923446 9 56 theme motifs 1561:1566 arg1 identification 1502:1515 identification 1502:1515 identification of the metal ion and carbohydrate adherence motifs on both SRCRs and AgI/II homologs 1502:1600 This study concludes that identification of the metal ion and carbohydrate adherence motifs on both SRCRs and AgI/II homologs could lead to the development of anti-adhesive inhibitors that could deter the adherence of pathogenic oral streptococci and thereby prevent the onset of infections. 24923446 2 57 theme GP340 532:536 arg1 GP340 532:536 GP340 532:536 GP340 532:536 Studying this interaction using recombinant proteins, we observed that calcium increases the conformational stability of the scavenger-rich cysteine repeat (SRCRs) domains of GP340. 24923446 2 57 theme GP340 532:536 arg1 domains 521:527 the scavenger-rich cysteine repeat (SRCRs) domains 478:527 the scavenger-rich cysteine repeat (SRCRs) domains of GP340 478:536 Studying this interaction using recombinant proteins, we observed that calcium increases the conformational stability of the scavenger-rich cysteine repeat (SRCRs) domains of GP340. 24923446 8 58 theme distinct 1323:1330 arg1 adherence/aggregation 1349:1369 distinct species-specific adherence/aggregation 1323:1369 distinct species-specific adherence/aggregation between Streptococcus mutans AgI/II and Streptococcus gordonii SspB in their interaction with the SRCRs 1323:1473 Finally, we show distinct species-specific adherence/aggregation between Streptococcus mutans AgI/II and Streptococcus gordonii SspB in their interaction with the SRCRs. 24923446 0 59 theme I/II 173:176 arg1 homologs 178:185 antigen I/II homologs 165:185 antigen I/II homologs 165:185 The calcium-induced conformation and glycosylation of scavenger-rich cysteine repeat (SRCR) domains of glycoprotein 340 influence the high affinity interaction with antigen I/II homologs. 24923446 0 60 gly glycosylation 37:49 arg1 domains 92:98 scavenger-rich cysteine repeat (SRCR) domains 54:98 scavenger-rich cysteine repeat (SRCR) domains of glycoprotein 340 54:118 The calcium-induced conformation and glycosylation of scavenger-rich cysteine repeat (SRCR) domains of glycoprotein 340 influence the high affinity interaction with antigen I/II homologs. 24923446 0 60 gly glycosylation 37:49 arg1 340 116:118 glycoprotein 340 103:118 glycoprotein 340 103:118 The calcium-induced conformation and glycosylation of scavenger-rich cysteine repeat (SRCR) domains of glycoprotein 340 influence the high affinity interaction with antigen I/II homologs. 24923446 5 61 theme SRCR 842:845 arg1 GP340 857:861 GP340 857:861 GP340 857:861 This study also establishes that a single SRCR domain of GP340 contains the two surfaces to which the apical and C-terminal regions of AgI/II noncompetitively adhere. 24923446 5 61 theme SRCR 842:845 arg1 domain 847:852 a single SRCR domain 833:852 a single SRCR domain of GP340 833:861 This study also establishes that a single SRCR domain of GP340 contains the two surfaces to which the apical and C-terminal regions of AgI/II noncompetitively adhere. 24923446 6 62 theme tandem 1015:1020 arg1 domains 1027:1033 the three tandem SRCR domains 1005:1033 the three tandem SRCR domains 1005:1033 Compared with the single SRCR domain, the three tandem SRCR domains displayed a collective/cooperative increase in their bacterial adherence and aggregation. 24923446 2 63 theme repeat 506:511 arg1 GP340 532:536 GP340 532:536 GP340 532:536 Studying this interaction using recombinant proteins, we observed that calcium increases the conformational stability of the scavenger-rich cysteine repeat (SRCRs) domains of GP340. 24923446 2 63 theme repeat 506:511 arg1 domains 521:527 the scavenger-rich cysteine repeat (SRCRs) domains 478:527 the scavenger-rich cysteine repeat (SRCRs) domains of GP340 478:536 Studying this interaction using recombinant proteins, we observed that calcium increases the conformational stability of the scavenger-rich cysteine repeat (SRCRs) domains of GP340. 24923446 9 64 dep deter 1671:1675 arg1 prevent 1735:1741 prevent 1735:1741 prevent the onset of infections 1735:1765 This study concludes that identification of the metal ion and carbohydrate adherence motifs on both SRCRs and AgI/II homologs could lead to the development of anti-adhesive inhibitors that could deter the adherence of pathogenic oral streptococci and thereby prevent the onset of infections. 24923446 2 65 theme scavenger-rich 482:495 arg1 repeat 506:511 scavenger-rich cysteine repeat 482:511 the scavenger-rich cysteine repeat (SRCRs) domains of GP340 478:536 Studying this interaction using recombinant proteins, we observed that calcium increases the conformational stability of the scavenger-rich cysteine repeat (SRCRs) domains of GP340. 24923446 2 65 theme scavenger-rich 482:495 arg1 SRCRs 514:518 SRCRs 514:518 SRCRs 514:518 Studying this interaction using recombinant proteins, we observed that calcium increases the conformational stability of the scavenger-rich cysteine repeat (SRCRs) domains of GP340. 24923446 1 66 dep antigen 283:289 arg1 AgI/II 297:302 AgI/II 297:302 AgI/II 297:302 Oral streptococci adhere to tooth-immobilized glycoprotein 340 (GP340) via the surface protein antigen I/II (AgI/II) and its homologs as the first step in pathogenesis. 24923446 1 66 dep antigen 283:289 arg1 I/II 291:294 I/II 291:294 the surface protein antigen I/II (AgI/II) 263:303 Oral streptococci adhere to tooth-immobilized glycoprotein 340 (GP340) via the surface protein antigen I/II (AgI/II) and its homologs as the first step in pathogenesis. 24923446 0 67 dep conformation 20:31 arg1 The 0:2 The 0:2 The 0:2 The calcium-induced conformation and glycosylation of scavenger-rich cysteine repeat (SRCR) domains of glycoprotein 340 influence the high affinity interaction with antigen I/II homologs. 24923446 8 68 from adherence/aggregation 1349:1369 arg1 interaction 1448:1458 their interaction 1442:1458 their interaction with the SRCRs 1442:1473 Finally, we show distinct species-specific adherence/aggregation between Streptococcus mutans AgI/II and Streptococcus gordonii SspB in their interaction with the SRCRs. 24923446 2 69 theme domains 521:527 arg1 stability 465:473 the conformational stability 446:473 the conformational stability of the scavenger-rich cysteine repeat (SRCRs) domains of GP340 446:536 Studying this interaction using recombinant proteins, we observed that calcium increases the conformational stability of the scavenger-rich cysteine repeat (SRCRs) domains of GP340. 24923446 4 70 theme present 778:784 arg1 carbohydrates 764:776 the O-linked carbohydrates 751:776 the O-linked carbohydrates present on the SRCRs 751:797 This interaction is significantly dependent on the O-linked carbohydrates present on the SRCRs. 24923446 0 71 theme 340 116:118 arg1 domains 92:98 scavenger-rich cysteine repeat (SRCR) domains 54:98 scavenger-rich cysteine repeat (SRCR) domains of glycoprotein 340 54:118 The calcium-induced conformation and glycosylation of scavenger-rich cysteine repeat (SRCR) domains of glycoprotein 340 influence the high affinity interaction with antigen I/II homologs. 24923446 0 71 theme 340 116:118 arg1 340 116:118 glycoprotein 340 103:118 glycoprotein 340 103:118 The calcium-induced conformation and glycosylation of scavenger-rich cysteine repeat (SRCR) domains of glycoprotein 340 influence the high affinity interaction with antigen I/II homologs. 24923446 0 72 theme calcium-induced 4:18 arg1 conformation 20:31 calcium-induced conformation 4:31 calcium-induced conformation 4:31 The calcium-induced conformation and glycosylation of scavenger-rich cysteine repeat (SRCR) domains of glycoprotein 340 influence the high affinity interaction with antigen I/II homologs. 24923446 5 73 theme AgI/II 935:940 arg1 regions 924:930 the apical and C-terminal regions 898:930 the apical and C-terminal regions of AgI/II 898:940 This study also establishes that a single SRCR domain of GP340 contains the two surfaces to which the apical and C-terminal regions of AgI/II noncompetitively adhere. 24923446 7 74 theme aggregate 1183:1191 arg1 streptococci 1206:1217 aggregate several oral streptococci 1183:1217 aggregate several oral streptococci 1183:1217 The previously described SRCRP2 peptide that was shown to aggregate several oral streptococci displayed limited aggregation and also nonspecific adherence compared to SRCR domains. 24923446 9 75 from identification 1502:1515 arg1 SRCRs 1576:1580 SRCRs 1576:1580 SRCRs 1576:1580 This study concludes that identification of the metal ion and carbohydrate adherence motifs on both SRCRs and AgI/II homologs could lead to the development of anti-adhesive inhibitors that could deter the adherence of pathogenic oral streptococci and thereby prevent the onset of infections. 24923446 9 75 from identification 1502:1515 arg1 homologs 1593:1600 AgI/II homologs 1586:1600 AgI/II homologs 1586:1600 This study concludes that identification of the metal ion and carbohydrate adherence motifs on both SRCRs and AgI/II homologs could lead to the development of anti-adhesive inhibitors that could deter the adherence of pathogenic oral streptococci and thereby prevent the onset of infections. 24923446 0 76 gly glycoprotein 103:114 arg1 glycoprotein 103:114 glycoprotein 340 103:118 glycoprotein 340 103:118 The calcium-induced conformation and glycosylation of scavenger-rich cysteine repeat (SRCR) domains of glycoprotein 340 influence the high affinity interaction with antigen I/II homologs. 24923446 4 77 theme O-linked 755:762 arg1 carbohydrates 764:776 the O-linked carbohydrates 751:776 the O-linked carbohydrates present on the SRCRs 751:797 This interaction is significantly dependent on the O-linked carbohydrates present on the SRCRs. 24923446 1 78 theme tooth-immobilized 216:232 arg1 GP340 252:256 GP340 252:256 GP340 252:256 Oral streptococci adhere to tooth-immobilized glycoprotein 340 (GP340) via the surface protein antigen I/II (AgI/II) and its homologs as the first step in pathogenesis. 24923446 1 78 theme tooth-immobilized 216:232 arg1 340 247:249 tooth-immobilized glycoprotein 340 216:249 tooth-immobilized glycoprotein 340 (GP340) via the surface protein antigen I/II (AgI/II) and its homologs 216:320 Oral streptococci adhere to tooth-immobilized glycoprotein 340 (GP340) via the surface protein antigen I/II (AgI/II) and its homologs as the first step in pathogenesis. 24923446 3 79 theme SRCR 641:644 arg1 conformation 646:657 the calcium-induced SRCR conformation 621:657 the calcium-induced SRCR conformation in an immobilized state and not in solution 621:701 Our results also show that AgI/II adheres specifically with nanomolar affinity to the calcium-induced SRCR conformation in an immobilized state and not in solution. 24923446 7 80 theme limited 1229:1235 arg1 aggregation 1237:1247 limited aggregation 1229:1247 limited aggregation 1229:1247 The previously described SRCRP2 peptide that was shown to aggregate several oral streptococci displayed limited aggregation and also nonspecific adherence compared to SRCR domains. 24923446 0 81 theme cysteine 69:76 arg1 domains 92:98 scavenger-rich cysteine repeat (SRCR) domains 54:98 scavenger-rich cysteine repeat (SRCR) domains of glycoprotein 340 54:118 The calcium-induced conformation and glycosylation of scavenger-rich cysteine repeat (SRCR) domains of glycoprotein 340 influence the high affinity interaction with antigen I/II homologs. 24923446 0 81 theme cysteine 69:76 arg1 340 116:118 glycoprotein 340 103:118 glycoprotein 340 103:118 The calcium-induced conformation and glycosylation of scavenger-rich cysteine repeat (SRCR) domains of glycoprotein 340 influence the high affinity interaction with antigen I/II homologs. 24923446 2 82 theme conformational 450:463 arg1 stability 465:473 the conformational stability 446:473 the conformational stability of the scavenger-rich cysteine repeat (SRCRs) domains of GP340 446:536 Studying this interaction using recombinant proteins, we observed that calcium increases the conformational stability of the scavenger-rich cysteine repeat (SRCRs) domains of GP340. 24923446 9 83 theme oral 1705:1708 arg1 streptococci 1710:1721 pathogenic oral streptococci 1694:1721 pathogenic oral streptococci 1694:1721 This study concludes that identification of the metal ion and carbohydrate adherence motifs on both SRCRs and AgI/II homologs could lead to the development of anti-adhesive inhibitors that could deter the adherence of pathogenic oral streptococci and thereby prevent the onset of infections. 24923446 3 84 theme immobilized 665:675 arg1 state 677:681 an immobilized state 662:681 an immobilized state 662:681 Our results also show that AgI/II adheres specifically with nanomolar affinity to the calcium-induced SRCR conformation in an immobilized state and not in solution. 24923446 5 85 theme GP340 857:861 arg1 GP340 857:861 GP340 857:861 GP340 857:861 This study also establishes that a single SRCR domain of GP340 contains the two surfaces to which the apical and C-terminal regions of AgI/II noncompetitively adhere. 24923446 5 85 theme GP340 857:861 arg1 domain 847:852 a single SRCR domain 833:852 a single SRCR domain of GP340 833:861 This study also establishes that a single SRCR domain of GP340 contains the two surfaces to which the apical and C-terminal regions of AgI/II noncompetitively adhere. 24923446 7 86 theme oral 1201:1204 arg1 streptococci 1206:1217 aggregate several oral streptococci 1183:1217 aggregate several oral streptococci 1183:1217 The previously described SRCRP2 peptide that was shown to aggregate several oral streptococci displayed limited aggregation and also nonspecific adherence compared to SRCR domains. 24239648 0 0 theme subunit 54:60 arg1 gene 62:65 mammalian gonadotropin β subunit gene 29:65 mammalian gonadotropin β subunit gene 29:65 The role of the 3' region of mammalian gonadotropin β subunit gene in the luteinizing hormone to chorionic gonadotropin evolution. 24239648 3 1 theme CTP-like 387:394 arg1 sequences 396:404 CTP-like sequences 387:404 CTP-like sequences 387:404 Although CTP-like sequences are encrypted in the LHβ genes of several mammals, the CGβ subunit developed only in primates and equids. 24239648 1 2 theme CGβ 131:133 arg1 subunits 135:142 CGβ subunits 131:142 CGβ subunits 131:142 CGβ subunits comprise a unique carboxyl-terminal peptide (CTP) that has multiple O-linked glycans and extends serum half-life of the protein. 24239648 6 3 theme serum 921:925 arg1 half-life 927:935 serum half-life 921:935 serum half-life 921:935 O-glycan deficiency and the associated incapacity to extend serum half-life is a major drawback of the boCTP. 24239648 0 4 theme β 52:52 arg1 gene 62:65 mammalian gonadotropin β subunit gene 29:65 mammalian gonadotropin β subunit gene 29:65 The role of the 3' region of mammalian gonadotropin β subunit gene in the luteinizing hormone to chorionic gonadotropin evolution. 24239648 0 5 from role 4:7 arg1 hormone 86:92 the luteinizing hormone 70:92 the luteinizing hormone to chorionic gonadotropin evolution 70:128 The role of the 3' region of mammalian gonadotropin β subunit gene in the luteinizing hormone to chorionic gonadotropin evolution. 24239648 2 6 theme untranslated 318:329 arg1 region 331:336 a previously untranslated region 305:336 a previously untranslated region of the LHβ gene 305:352 It has evolved by incorporating a previously untranslated region of the LHβ gene into the reading frame. 24239648 4 7 theme CGβ-CTP 676:682 arg1 characteristics 643:657 key characteristics 639:657 key characteristics of the human (h) CGβ-CTP 639:682 To study this restriction in evolution, we examined whether the cryptic CTP decoded from the bovine LHβ gene (boCTP) possesses key characteristics of the human (h) CGβ-CTP. 24239648 0 8 theme gene 62:65 arg1 region 19:24 the 3' region 12:24 the 3' region of mammalian gonadotropin β subunit gene 12:65 The role of the 3' region of mammalian gonadotropin β subunit gene in the luteinizing hormone to chorionic gonadotropin evolution. 24239648 1 9 theme serum 241:245 arg1 half-life 247:255 serum half-life 241:255 serum half-life of the protein 241:270 CGβ subunits comprise a unique carboxyl-terminal peptide (CTP) that has multiple O-linked glycans and extends serum half-life of the protein. 24239648 0 10 theme luteinizing 74:84 arg1 hormone 86:92 the luteinizing hormone 70:92 the luteinizing hormone to chorionic gonadotropin evolution 70:128 The role of the 3' region of mammalian gonadotropin β subunit gene in the luteinizing hormone to chorionic gonadotropin evolution. 24239648 4 11 theme key 639:641 arg1 characteristics 643:657 key characteristics 639:657 key characteristics of the human (h) CGβ-CTP 639:682 To study this restriction in evolution, we examined whether the cryptic CTP decoded from the bovine LHβ gene (boCTP) possesses key characteristics of the human (h) CGβ-CTP. 24239648 1 12 theme unique 155:160 arg1 CTP 189:191 CTP 189:191 CTP 189:191 CGβ subunits comprise a unique carboxyl-terminal peptide (CTP) that has multiple O-linked glycans and extends serum half-life of the protein. 24239648 1 12 theme unique 155:160 arg1 peptide 180:186 a unique carboxyl-terminal peptide 153:186 a unique carboxyl-terminal peptide (CTP) that has multiple O-linked glycans and extends serum half-life of the protein 153:270 CGβ subunits comprise a unique carboxyl-terminal peptide (CTP) that has multiple O-linked glycans and extends serum half-life of the protein. 24239648 4 13 contain possesses 629:637 arg1 CTP 584:586 the cryptic CTP 572:586 the cryptic CTP decoded from the bovine LHβ gene (boCTP) 572:627 To study this restriction in evolution, we examined whether the cryptic CTP decoded from the bovine LHβ gene (boCTP) possesses key characteristics of the human (h) CGβ-CTP. 24239648 4 13 contain possesses 629:637 arg2 characteristics 643:657 key characteristics 639:657 key characteristics of the human (h) CGβ-CTP 639:682 To study this restriction in evolution, we examined whether the cryptic CTP decoded from the bovine LHβ gene (boCTP) possesses key characteristics of the human (h) CGβ-CTP. 24239648 5 14 theme hormone 738:744 arg1 biosynthesis 746:757 hormone biosynthesis 738:757 hormone biosynthesis 738:757 The boCTP does not impede several crucial aspects of hormone biosynthesis, but compared to the hCGβ-CTP, the stretch lacks O-glycans and determinants for circulatory survival. 24239648 5 15 theme circulatory 839:849 arg1 survival 851:858 circulatory survival 839:858 circulatory survival 839:858 The boCTP does not impede several crucial aspects of hormone biosynthesis, but compared to the hCGβ-CTP, the stretch lacks O-glycans and determinants for circulatory survival. 24239648 5 16 theme several 711:717 arg1 aspects 727:733 several crucial aspects 711:733 several crucial aspects of hormone biosynthesis 711:757 The boCTP does not impede several crucial aspects of hormone biosynthesis, but compared to the hCGβ-CTP, the stretch lacks O-glycans and determinants for circulatory survival. 24239648 1 17 link O-linked 212:219 arg1 glycans 221:227 multiple O-linked glycans 203:227 multiple O-linked glycans 203:227 CGβ subunits comprise a unique carboxyl-terminal peptide (CTP) that has multiple O-linked glycans and extends serum half-life of the protein. 24239648 4 18 theme human 666:670 arg1 CGβ-CTP 676:682 the human (h) CGβ-CTP 662:682 the human (h) CGβ-CTP 662:682 To study this restriction in evolution, we examined whether the cryptic CTP decoded from the bovine LHβ gene (boCTP) possesses key characteristics of the human (h) CGβ-CTP. 24239648 2 19 theme gene 349:352 arg1 region 331:336 a previously untranslated region 305:336 a previously untranslated region of the LHβ gene 305:352 It has evolved by incorporating a previously untranslated region of the LHβ gene into the reading frame. 24239648 5 20 theme crucial 719:725 arg1 aspects 727:733 several crucial aspects 711:733 several crucial aspects of hormone biosynthesis 711:757 The boCTP does not impede several crucial aspects of hormone biosynthesis, but compared to the hCGβ-CTP, the stretch lacks O-glycans and determinants for circulatory survival. 24239648 6 21 theme associated 889:898 arg1 incapacity 900:909 the associated incapacity to extend serum half-life 885:935 the associated incapacity to extend serum half-life 885:935 O-glycan deficiency and the associated incapacity to extend serum half-life is a major drawback of the boCTP. 24239648 6 21 theme associated 889:898 arg1 drawback 948:955 a major drawback 940:955 a major drawback of the boCTP 940:968 O-glycan deficiency and the associated incapacity to extend serum half-life is a major drawback of the boCTP. 24239648 6 21 theme associated 889:898 arg1 deficiency 870:879 O-glycan deficiency 861:879 O-glycan deficiency 861:879 O-glycan deficiency and the associated incapacity to extend serum half-life is a major drawback of the boCTP. 24239648 2 22 theme LHβ 345:347 arg1 gene 349:352 the LHβ gene 341:352 the LHβ gene 341:352 It has evolved by incorporating a previously untranslated region of the LHβ gene into the reading frame. 24239648 4 23 theme h 673:673 arg1 CGβ-CTP 676:682 the human (h) CGβ-CTP 662:682 the human (h) CGβ-CTP 662:682 To study this restriction in evolution, we examined whether the cryptic CTP decoded from the bovine LHβ gene (boCTP) possesses key characteristics of the human (h) CGβ-CTP. 24239648 3 24 theme LHβ 427:429 arg1 genes 431:435 the LHβ genes 423:435 the LHβ genes of several mammals 423:454 Although CTP-like sequences are encrypted in the LHβ genes of several mammals, the CGβ subunit developed only in primates and equids. 24239648 3 25 theme CGβ 461:463 arg1 subunit 465:471 the CGβ subunit 457:471 the CGβ subunit 457:471 Although CTP-like sequences are encrypted in the LHβ genes of several mammals, the CGβ subunit developed only in primates and equids. 24239648 5 26 theme biosynthesis 746:757 arg1 aspects 727:733 several crucial aspects 711:733 several crucial aspects of hormone biosynthesis 711:757 The boCTP does not impede several crucial aspects of hormone biosynthesis, but compared to the hCGβ-CTP, the stretch lacks O-glycans and determinants for circulatory survival. 24239648 1 27 theme protein 264:270 arg1 half-life 247:255 serum half-life 241:255 serum half-life of the protein 241:270 CGβ subunits comprise a unique carboxyl-terminal peptide (CTP) that has multiple O-linked glycans and extends serum half-life of the protein. 24239648 0 28 theme gonadotropin 107:118 arg1 evolution 120:128 chorionic gonadotropin evolution 97:128 chorionic gonadotropin evolution 97:128 The role of the 3' region of mammalian gonadotropin β subunit gene in the luteinizing hormone to chorionic gonadotropin evolution. 24239648 1 29 theme carboxyl-terminal 162:178 arg1 CTP 189:191 CTP 189:191 CTP 189:191 CGβ subunits comprise a unique carboxyl-terminal peptide (CTP) that has multiple O-linked glycans and extends serum half-life of the protein. 24239648 1 29 theme carboxyl-terminal 162:178 arg1 peptide 180:186 a unique carboxyl-terminal peptide 153:186 a unique carboxyl-terminal peptide (CTP) that has multiple O-linked glycans and extends serum half-life of the protein 153:270 CGβ subunits comprise a unique carboxyl-terminal peptide (CTP) that has multiple O-linked glycans and extends serum half-life of the protein. 24239648 7 30 theme alternative 1048:1058 arg1 mechanisms 1060:1069 consequently alternative mechanisms 1035:1069 consequently alternative mechanisms 1035:1069 This may explain why LH did not evolve into CG in ruminants and consequently alternative mechanisms evolved to delay luteolysis early in gestation. 24239648 6 31 theme O-glycan 861:868 arg1 drawback 948:955 a major drawback 940:955 a major drawback of the boCTP 940:968 O-glycan deficiency and the associated incapacity to extend serum half-life is a major drawback of the boCTP. 24239648 6 31 theme O-glycan 861:868 arg1 incapacity 900:909 the associated incapacity to extend serum half-life 885:935 the associated incapacity to extend serum half-life 885:935 O-glycan deficiency and the associated incapacity to extend serum half-life is a major drawback of the boCTP. 24239648 6 31 theme O-glycan 861:868 arg1 deficiency 870:879 O-glycan deficiency 861:879 O-glycan deficiency 861:879 O-glycan deficiency and the associated incapacity to extend serum half-life is a major drawback of the boCTP. 24239648 0 32 theme chorionic 97:105 arg1 evolution 120:128 chorionic gonadotropin evolution 97:128 chorionic gonadotropin evolution 97:128 The role of the 3' region of mammalian gonadotropin β subunit gene in the luteinizing hormone to chorionic gonadotropin evolution. 24239648 2 33 theme reading 363:369 arg1 frame 371:375 the reading frame 359:375 the reading frame 359:375 It has evolved by incorporating a previously untranslated region of the LHβ gene into the reading frame. 24239648 4 34 theme LHβ 612:614 arg1 boCTP 622:626 boCTP 622:626 boCTP 622:626 To study this restriction in evolution, we examined whether the cryptic CTP decoded from the bovine LHβ gene (boCTP) possesses key characteristics of the human (h) CGβ-CTP. 24239648 4 34 theme LHβ 612:614 arg1 gene 616:619 the bovine LHβ gene 601:619 the bovine LHβ gene (boCTP) 601:627 To study this restriction in evolution, we examined whether the cryptic CTP decoded from the bovine LHβ gene (boCTP) possesses key characteristics of the human (h) CGβ-CTP. 24239648 1 35 contain has 199:201 arg1 CTP 189:191 CTP 189:191 CTP 189:191 CGβ subunits comprise a unique carboxyl-terminal peptide (CTP) that has multiple O-linked glycans and extends serum half-life of the protein. 24239648 1 35 contain has 199:201 arg2 glycans 221:227 multiple O-linked glycans 203:227 multiple O-linked glycans 203:227 CGβ subunits comprise a unique carboxyl-terminal peptide (CTP) that has multiple O-linked glycans and extends serum half-life of the protein. 24239648 1 35 contain has 199:201 arg1 peptide 180:186 a unique carboxyl-terminal peptide 153:186 a unique carboxyl-terminal peptide (CTP) that has multiple O-linked glycans and extends serum half-life of the protein 153:270 CGβ subunits comprise a unique carboxyl-terminal peptide (CTP) that has multiple O-linked glycans and extends serum half-life of the protein. 24239648 3 36 theme mammals 448:454 arg1 genes 431:435 the LHβ genes 423:435 the LHβ genes of several mammals 423:454 Although CTP-like sequences are encrypted in the LHβ genes of several mammals, the CGβ subunit developed only in primates and equids. 24239648 0 37 theme region 19:24 arg1 role 4:7 The role 0:7 The role of the 3' region of mammalian gonadotropin β subunit gene in the luteinizing hormone to chorionic gonadotropin evolution. 0:129 The role of the 3' region of mammalian gonadotropin β subunit gene in the luteinizing hormone to chorionic gonadotropin evolution. 24239648 7 38 from CG 1015:1016 arg1 ruminants 1021:1029 ruminants 1021:1029 ruminants 1021:1029 This may explain why LH did not evolve into CG in ruminants and consequently alternative mechanisms evolved to delay luteolysis early in gestation. 24239648 4 39 theme bovine 605:610 arg1 boCTP 622:626 boCTP 622:626 boCTP 622:626 To study this restriction in evolution, we examined whether the cryptic CTP decoded from the bovine LHβ gene (boCTP) possesses key characteristics of the human (h) CGβ-CTP. 24239648 4 39 theme bovine 605:610 arg1 gene 616:619 the bovine LHβ gene 601:619 the bovine LHβ gene (boCTP) 601:627 To study this restriction in evolution, we examined whether the cryptic CTP decoded from the bovine LHβ gene (boCTP) possesses key characteristics of the human (h) CGβ-CTP. 24239648 6 40 theme major 942:946 arg1 drawback 948:955 a major drawback 940:955 a major drawback of the boCTP 940:968 O-glycan deficiency and the associated incapacity to extend serum half-life is a major drawback of the boCTP. 24239648 6 40 theme major 942:946 arg1 incapacity 900:909 the associated incapacity to extend serum half-life 885:935 the associated incapacity to extend serum half-life 885:935 O-glycan deficiency and the associated incapacity to extend serum half-life is a major drawback of the boCTP. 24239648 6 40 theme major 942:946 arg1 deficiency 870:879 O-glycan deficiency 861:879 O-glycan deficiency 861:879 O-glycan deficiency and the associated incapacity to extend serum half-life is a major drawback of the boCTP. 24239648 6 41 theme boCTP 964:968 arg1 drawback 948:955 a major drawback 940:955 a major drawback of the boCTP 940:968 O-glycan deficiency and the associated incapacity to extend serum half-life is a major drawback of the boCTP. 24239648 6 41 theme boCTP 964:968 arg1 incapacity 900:909 the associated incapacity to extend serum half-life 885:935 the associated incapacity to extend serum half-life 885:935 O-glycan deficiency and the associated incapacity to extend serum half-life is a major drawback of the boCTP. 24239648 6 41 theme boCTP 964:968 arg1 deficiency 870:879 O-glycan deficiency 861:879 O-glycan deficiency 861:879 O-glycan deficiency and the associated incapacity to extend serum half-life is a major drawback of the boCTP. 24239648 3 42 theme several 440:446 arg1 mammals 448:454 several mammals 440:454 several mammals 440:454 Although CTP-like sequences are encrypted in the LHβ genes of several mammals, the CGβ subunit developed only in primates and equids. 24239648 0 43 theme gonadotropin 39:50 arg1 gene 62:65 mammalian gonadotropin β subunit gene 29:65 mammalian gonadotropin β subunit gene 29:65 The role of the 3' region of mammalian gonadotropin β subunit gene in the luteinizing hormone to chorionic gonadotropin evolution. 24239648 4 44 theme cryptic 576:582 arg1 CTP 584:586 the cryptic CTP 572:586 the cryptic CTP decoded from the bovine LHβ gene (boCTP) 572:627 To study this restriction in evolution, we examined whether the cryptic CTP decoded from the bovine LHβ gene (boCTP) possesses key characteristics of the human (h) CGβ-CTP. 24239648 1 45 theme multiple 203:210 arg1 glycans 221:227 multiple O-linked glycans 203:227 multiple O-linked glycans 203:227 CGβ subunits comprise a unique carboxyl-terminal peptide (CTP) that has multiple O-linked glycans and extends serum half-life of the protein. 24239648 0 46 theme mammalian 29:37 arg1 gene 62:65 mammalian gonadotropin β subunit gene 29:65 mammalian gonadotropin β subunit gene 29:65 The role of the 3' region of mammalian gonadotropin β subunit gene in the luteinizing hormone to chorionic gonadotropin evolution. 24239648 1 47 theme O-linked 212:219 arg1 glycans 221:227 multiple O-linked glycans 203:227 multiple O-linked glycans 203:227 CGβ subunits comprise a unique carboxyl-terminal peptide (CTP) that has multiple O-linked glycans and extends serum half-life of the protein. 28903979 2 0 theme metabolic 373:381 arg1 adaptation 383:392 metabolic adaptation 373:392 metabolic adaptation to starvation 373:406 Here we demonstrate that O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is required for glucagon-stimulated liver autophagy and metabolic adaptation to starvation. 28903979 2 1 link O-linked 257:264 arg1 transferase 299:309 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase 257:309 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) 257:315 Here we demonstrate that O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is required for glucagon-stimulated liver autophagy and metabolic adaptation to starvation. 28903979 2 1 link O-linked 257:264 arg1 OGT 312:314 OGT 312:314 OGT 312:314 Here we demonstrate that O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is required for glucagon-stimulated liver autophagy and metabolic adaptation to starvation. 28903979 5 2 theme OGT 845:847 arg1 phosphorylation 849:863 OGT phosphorylation 845:863 OGT phosphorylation 845:863 These findings uncover a signaling cascade by which starvation promotes autophagy through OGT phosphorylation and establish the importance of O-GlcNAc signaling in coupling liver autophagy to nutrient homeostasis. 28903979 4 3 theme calcium 544:550 arg1 signaling 552:560 glucagon-induced calcium signaling 527:560 glucagon-induced calcium signaling 527:560 Upon glucagon-induced calcium signaling, calcium/calmodulin-dependent kinase II (CaMKII) phosphorylates OGT, which in turn promotes O-GlcNAc modification and activation of Ulk proteins by potentiating AMPK-dependent phosphorylation. 28903979 4 4 theme glucagon-induced 527:542 arg1 signaling 552:560 glucagon-induced calcium signaling 527:560 glucagon-induced calcium signaling 527:560 Upon glucagon-induced calcium signaling, calcium/calmodulin-dependent kinase II (CaMKII) phosphorylates OGT, which in turn promotes O-GlcNAc modification and activation of Ulk proteins by potentiating AMPK-dependent phosphorylation. 28903979 4 5 theme proteins 698:705 arg1 activation 680:689 activation 680:689 activation of Ulk proteins 680:705 Upon glucagon-induced calcium signaling, calcium/calmodulin-dependent kinase II (CaMKII) phosphorylates OGT, which in turn promotes O-GlcNAc modification and activation of Ulk proteins by potentiating AMPK-dependent phosphorylation. 28903979 4 5 theme proteins 698:705 arg1 modification 663:674 O-GlcNAc modification 654:674 O-GlcNAc modification 654:674 Upon glucagon-induced calcium signaling, calcium/calmodulin-dependent kinase II (CaMKII) phosphorylates OGT, which in turn promotes O-GlcNAc modification and activation of Ulk proteins by potentiating AMPK-dependent phosphorylation. 28903979 5 6 theme nutrient 947:954 arg1 homeostasis 956:966 nutrient homeostasis 947:966 nutrient homeostasis 947:966 These findings uncover a signaling cascade by which starvation promotes autophagy through OGT phosphorylation and establish the importance of O-GlcNAc signaling in coupling liver autophagy to nutrient homeostasis. 28903979 3 7 theme autophagic 457:466 arg1 flux 468:471 autophagic flux 457:471 autophagic flux 457:471 Genetic ablation of OGT in mouse livers reduces autophagic flux and the production of glucose and ketone bodies. 28903979 5 8 from importance 883:892 arg1 autophagy 934:942 coupling liver autophagy 919:942 coupling liver autophagy to nutrient homeostasis 919:966 These findings uncover a signaling cascade by which starvation promotes autophagy through OGT phosphorylation and establish the importance of O-GlcNAc signaling in coupling liver autophagy to nutrient homeostasis. 28903979 2 9 theme O-GlcNAc 289:296 arg1 transferase 299:309 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase 257:309 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) 257:315 Here we demonstrate that O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is required for glucagon-stimulated liver autophagy and metabolic adaptation to starvation. 28903979 2 9 theme O-GlcNAc 289:296 arg1 OGT 312:314 OGT 312:314 OGT 312:314 Here we demonstrate that O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is required for glucagon-stimulated liver autophagy and metabolic adaptation to starvation. 28903979 4 10 mod modification 663:674 arg1 proteins 698:705 Ulk proteins 694:705 Ulk proteins 694:705 Upon glucagon-induced calcium signaling, calcium/calmodulin-dependent kinase II (CaMKII) phosphorylates OGT, which in turn promotes O-GlcNAc modification and activation of Ulk proteins by potentiating AMPK-dependent phosphorylation. 28903979 4 10 mod modification 663:674 arg3 O-GlcNAc 654:661 O-GlcNAc modification 654:674 O-GlcNAc modification 654:674 Upon glucagon-induced calcium signaling, calcium/calmodulin-dependent kinase II (CaMKII) phosphorylates OGT, which in turn promotes O-GlcNAc modification and activation of Ulk proteins by potentiating AMPK-dependent phosphorylation. 28903979 1 11 theme other 174:178 arg1 organs 180:185 other organs 174:185 other organs 174:185 Starvation induces liver autophagy, which is thought to provide nutrients for use by other organs and thereby maintain whole-body homeostasis. 28903979 0 12 theme O-GlcNAc 18:25 arg1 signaling 27:35 Calcium-dependent O-GlcNAc signaling 0:35 Calcium-dependent O-GlcNAc signaling 0:35 Calcium-dependent O-GlcNAc signaling drives liver autophagy in adaptation to starvation. 28903979 3 13 from ablation 417:424 arg1 livers 442:447 mouse livers 436:447 mouse livers 436:447 Genetic ablation of OGT in mouse livers reduces autophagic flux and the production of glucose and ketone bodies. 28903979 0 14 theme Calcium-dependent 0:16 arg1 signaling 27:35 Calcium-dependent O-GlcNAc signaling 0:35 Calcium-dependent O-GlcNAc signaling 0:35 Calcium-dependent O-GlcNAc signaling drives liver autophagy in adaptation to starvation. 28903979 1 15 theme liver 108:112 arg1 autophagy 114:122 liver autophagy 108:122 liver autophagy 108:122 Starvation induces liver autophagy, which is thought to provide nutrients for use by other organs and thereby maintain whole-body homeostasis. 28903979 5 16 theme O-GlcNAc 897:904 arg1 signaling 906:914 O-GlcNAc signaling 897:914 O-GlcNAc signaling 897:914 These findings uncover a signaling cascade by which starvation promotes autophagy through OGT phosphorylation and establish the importance of O-GlcNAc signaling in coupling liver autophagy to nutrient homeostasis. 28903979 5 17 theme signaling 906:914 arg1 importance 883:892 the importance 879:892 the importance of O-GlcNAc signaling in coupling liver autophagy to nutrient homeostasis 879:966 These findings uncover a signaling cascade by which starvation promotes autophagy through OGT phosphorylation and establish the importance of O-GlcNAc signaling in coupling liver autophagy to nutrient homeostasis. 28903979 5 18 theme coupling 919:926 arg1 autophagy 934:942 coupling liver autophagy 919:942 coupling liver autophagy to nutrient homeostasis 919:966 These findings uncover a signaling cascade by which starvation promotes autophagy through OGT phosphorylation and establish the importance of O-GlcNAc signaling in coupling liver autophagy to nutrient homeostasis. 28903979 3 19 theme bodies 514:519 arg1 flux 468:471 autophagic flux 457:471 autophagic flux 457:471 Genetic ablation of OGT in mouse livers reduces autophagic flux and the production of glucose and ketone bodies. 28903979 3 19 theme bodies 514:519 arg1 production 481:490 the production 477:490 the production of glucose and ketone bodies 477:519 Genetic ablation of OGT in mouse livers reduces autophagic flux and the production of glucose and ketone bodies. 28903979 5 20 theme liver 928:932 arg1 autophagy 934:942 coupling liver autophagy 919:942 coupling liver autophagy to nutrient homeostasis 919:966 These findings uncover a signaling cascade by which starvation promotes autophagy through OGT phosphorylation and establish the importance of O-GlcNAc signaling in coupling liver autophagy to nutrient homeostasis. 28903979 5 21 theme signaling 780:788 arg1 cascade 790:796 a signaling cascade 778:796 a signaling cascade by which starvation promotes autophagy through OGT phosphorylation 778:863 These findings uncover a signaling cascade by which starvation promotes autophagy through OGT phosphorylation and establish the importance of O-GlcNAc signaling in coupling liver autophagy to nutrient homeostasis. 28903979 1 22 theme whole-body 208:217 arg1 homeostasis 219:229 whole-body homeostasis 208:229 whole-body homeostasis 208:229 Starvation induces liver autophagy, which is thought to provide nutrients for use by other organs and thereby maintain whole-body homeostasis. 28903979 0 23 theme liver 44:48 arg1 autophagy 50:58 liver autophagy 44:58 liver autophagy 44:58 Calcium-dependent O-GlcNAc signaling drives liver autophagy in adaptation to starvation. 28903979 3 24 theme mouse 436:440 arg1 livers 442:447 mouse livers 436:447 mouse livers 436:447 Genetic ablation of OGT in mouse livers reduces autophagic flux and the production of glucose and ketone bodies. 28903979 3 25 theme ketone 507:512 arg1 bodies 514:519 ketone bodies 507:519 ketone bodies 507:519 Genetic ablation of OGT in mouse livers reduces autophagic flux and the production of glucose and ketone bodies. 28903979 3 26 theme OGT 429:431 arg1 ablation 417:424 Genetic ablation 409:424 Genetic ablation of OGT in mouse livers 409:447 Genetic ablation of OGT in mouse livers reduces autophagic flux and the production of glucose and ketone bodies. 28903979 2 27 theme liver 353:357 arg1 autophagy 359:367 glucagon-stimulated liver autophagy 333:367 glucagon-stimulated liver autophagy 333:367 Here we demonstrate that O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is required for glucagon-stimulated liver autophagy and metabolic adaptation to starvation. 28903979 4 28 theme calcium/calmodulin-dependent 563:590 arg1 kinase 592:597 calcium/calmodulin-dependent kinase II 563:600 calcium/calmodulin-dependent kinase II (CaMKII) 563:609 Upon glucagon-induced calcium signaling, calcium/calmodulin-dependent kinase II (CaMKII) phosphorylates OGT, which in turn promotes O-GlcNAc modification and activation of Ulk proteins by potentiating AMPK-dependent phosphorylation. 28903979 4 28 theme calcium/calmodulin-dependent 563:590 arg1 CaMKII 603:608 CaMKII 603:608 CaMKII 603:608 Upon glucagon-induced calcium signaling, calcium/calmodulin-dependent kinase II (CaMKII) phosphorylates OGT, which in turn promotes O-GlcNAc modification and activation of Ulk proteins by potentiating AMPK-dependent phosphorylation. 28903979 2 29 theme glucagon-stimulated 333:351 arg1 autophagy 359:367 glucagon-stimulated liver autophagy 333:367 glucagon-stimulated liver autophagy 333:367 Here we demonstrate that O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is required for glucagon-stimulated liver autophagy and metabolic adaptation to starvation. 28903979 2 30 theme β-N-acetylglucosamine 266:286 arg1 transferase 299:309 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase 257:309 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) 257:315 Here we demonstrate that O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is required for glucagon-stimulated liver autophagy and metabolic adaptation to starvation. 28903979 2 30 theme β-N-acetylglucosamine 266:286 arg1 OGT 312:314 OGT 312:314 OGT 312:314 Here we demonstrate that O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is required for glucagon-stimulated liver autophagy and metabolic adaptation to starvation. 28903979 4 31 theme AMPK-dependent 723:736 arg1 phosphorylation 738:752 AMPK-dependent phosphorylation 723:752 AMPK-dependent phosphorylation 723:752 Upon glucagon-induced calcium signaling, calcium/calmodulin-dependent kinase II (CaMKII) phosphorylates OGT, which in turn promotes O-GlcNAc modification and activation of Ulk proteins by potentiating AMPK-dependent phosphorylation. 28903979 3 32 theme glucose 495:501 arg1 flux 468:471 autophagic flux 457:471 autophagic flux 457:471 Genetic ablation of OGT in mouse livers reduces autophagic flux and the production of glucose and ketone bodies. 28903979 3 32 theme glucose 495:501 arg1 production 481:490 the production 477:490 the production of glucose and ketone bodies 477:519 Genetic ablation of OGT in mouse livers reduces autophagic flux and the production of glucose and ketone bodies. 28903979 2 33 theme O-linked 257:264 arg1 transferase 299:309 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase 257:309 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) 257:315 Here we demonstrate that O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is required for glucagon-stimulated liver autophagy and metabolic adaptation to starvation. 28903979 2 33 theme O-linked 257:264 arg1 OGT 312:314 OGT 312:314 OGT 312:314 Here we demonstrate that O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is required for glucagon-stimulated liver autophagy and metabolic adaptation to starvation. 28903979 4 34 theme Ulk 694:696 arg1 proteins 698:705 Ulk proteins 694:705 Ulk proteins 694:705 Upon glucagon-induced calcium signaling, calcium/calmodulin-dependent kinase II (CaMKII) phosphorylates OGT, which in turn promotes O-GlcNAc modification and activation of Ulk proteins by potentiating AMPK-dependent phosphorylation. 28903979 4 35 theme O-GlcNAc 654:661 arg1 modification 663:674 O-GlcNAc modification 654:674 O-GlcNAc modification 654:674 Upon glucagon-induced calcium signaling, calcium/calmodulin-dependent kinase II (CaMKII) phosphorylates OGT, which in turn promotes O-GlcNAc modification and activation of Ulk proteins by potentiating AMPK-dependent phosphorylation. 28903979 3 36 theme Genetic 409:415 arg1 ablation 417:424 Genetic ablation 409:424 Genetic ablation of OGT in mouse livers 409:447 Genetic ablation of OGT in mouse livers reduces autophagic flux and the production of glucose and ketone bodies. 28204496 12 0 theme biomedical 2044:2053 arg1 initiatives 2064:2074 biomedical research initiatives 2044:2074 biomedical research initiatives 2044:2074 This study presents an example for guiding biomedical research initiatives, as well as medical and personal/family perspectives, regarding newly-identified genomic sequence differences. 28204496 11 1 from frequency 1660:1668 arg1 prevalence 1711:1720 prevalence 1711:1720 prevalence of CHST8 (c.299 C > T, R77W) across different ethnic groups 1711:1780 These findings, an allele frequency of 0.004357, and a 10-fold difference in prevalence of CHST8 (c.299 C > T, R77W) across different ethnic groups, suggest that this sequence represents a "passenger" distributed polymorphism, a simple sequence variant form of the enzyme having normal activity, rather than a "driver" disease-causing mutation that accounts for PSS. 28204496 1 2 from study 335:339 arg1 or 352:353 or 352:353 or 352:353 Expanded access to DNA sequencing now fosters ready detection of site-specific human genome alterations whose actual significance requires in-depth functional study to rule in or out disease-causing mutations. 28204496 11 3 theme 0.004357 1673:1680 arg1 findings 1640:1647 These findings 1634:1647 These findings 1634:1647 These findings, an allele frequency of 0.004357, and a 10-fold difference in prevalence of CHST8 (c.299 C > T, R77W) across different ethnic groups, suggest that this sequence represents a "passenger" distributed polymorphism, a simple sequence variant form of the enzyme having normal activity, rather than a "driver" disease-causing mutation that accounts for PSS. 28204496 11 3 theme 0.004357 1673:1680 arg1 difference 1697:1706 a 10-fold difference 1687:1706 a 10-fold difference in prevalence of CHST8 (c.299 C > T, R77W) across different ethnic groups 1687:1780 These findings, an allele frequency of 0.004357, and a 10-fold difference in prevalence of CHST8 (c.299 C > T, R77W) across different ethnic groups, suggest that this sequence represents a "passenger" distributed polymorphism, a simple sequence variant form of the enzyme having normal activity, rather than a "driver" disease-causing mutation that accounts for PSS. 28204496 11 3 theme 0.004357 1673:1680 arg1 frequency 1660:1668 an allele frequency 1650:1668 an allele frequency of 0.004357 1650:1680 These findings, an allele frequency of 0.004357, and a 10-fold difference in prevalence of CHST8 (c.299 C > T, R77W) across different ethnic groups, suggest that this sequence represents a "passenger" distributed polymorphism, a simple sequence variant form of the enzyme having normal activity, rather than a "driver" disease-causing mutation that accounts for PSS. 28204496 3 4 theme > 581:581 arg1 T 583:583 c.229 C > T 573:583 c.229 C > T 573:583 A recent whole-exome sequencing study identifies (c.229 C > T) in the GalNAc-4-ST1 glycosyltransferase (CHST8) as a disease-causing missense R77W mutation yielding the genodermatosis peeling skin syndrome (PSS) when homozygous. 28204496 11 5 theme simple 1863:1868 arg1 form 1887:1890 a simple sequence variant form 1861:1890 a simple sequence variant form of the enzyme having normal activity 1861:1927 These findings, an allele frequency of 0.004357, and a 10-fold difference in prevalence of CHST8 (c.299 C > T, R77W) across different ethnic groups, suggest that this sequence represents a "passenger" distributed polymorphism, a simple sequence variant form of the enzyme having normal activity, rather than a "driver" disease-causing mutation that accounts for PSS. 28204496 11 5 theme simple 1863:1868 arg1 polymorphism 1847:1858 polymorphism 1847:1858 polymorphism 1847:1858 These findings, an allele frequency of 0.004357, and a 10-fold difference in prevalence of CHST8 (c.299 C > T, R77W) across different ethnic groups, suggest that this sequence represents a "passenger" distributed polymorphism, a simple sequence variant form of the enzyme having normal activity, rather than a "driver" disease-causing mutation that accounts for PSS. 28204496 0 6 theme consistent 127:136 arg1 properties 116:125 normal properties 109:125 normal properties consistent with a simple sequence polymorphisim 109:173 The glycan-specific sulfotransferase (R77W)GalNAc-4-ST1 putatively responsible for peeling skin syndrome has normal properties consistent with a simple sequence polymorphisim. 28204496 8 7 theme catalytic 1292:1300 arg1 activity 1302:1309 catalytic activity 1292:1309 catalytic activity of GalNAc-4-ST1 completely equivalent between wild type and (R77W) sulfotransferases 1292:1394 We find expression, processing and catalytic activity of GalNAc-4-ST1 completely equivalent between wild type and (R77W) sulfotransferases. 28204496 7 8 link O-linked 1204:1211 arg1 oligosaccharides 1213:1228 O-linked oligosaccharides 1204:1228 O-linked oligosaccharides 1204:1228 However, GalNAc-4-ST1 has minimal activity toward glycosaminoglycans, instead modifying terminal β1,4-linked GalNAc on N- and O-linked oligosaccharides on specific glycoproteins. 28204496 11 9 from difference 1697:1706 arg1 prevalence 1711:1720 prevalence 1711:1720 prevalence of CHST8 (c.299 C > T, R77W) across different ethnic groups 1711:1780 These findings, an allele frequency of 0.004357, and a 10-fold difference in prevalence of CHST8 (c.299 C > T, R77W) across different ethnic groups, suggest that this sequence represents a "passenger" distributed polymorphism, a simple sequence variant form of the enzyme having normal activity, rather than a "driver" disease-causing mutation that accounts for PSS. 28204496 11 10 theme variant 1879:1885 arg1 form 1887:1890 a simple sequence variant form 1861:1890 a simple sequence variant form of the enzyme having normal activity 1861:1927 These findings, an allele frequency of 0.004357, and a 10-fold difference in prevalence of CHST8 (c.299 C > T, R77W) across different ethnic groups, suggest that this sequence represents a "passenger" distributed polymorphism, a simple sequence variant form of the enzyme having normal activity, rather than a "driver" disease-causing mutation that accounts for PSS. 28204496 11 10 theme variant 1879:1885 arg1 polymorphism 1847:1858 polymorphism 1847:1858 polymorphism 1847:1858 These findings, an allele frequency of 0.004357, and a 10-fold difference in prevalence of CHST8 (c.299 C > T, R77W) across different ethnic groups, suggest that this sequence represents a "passenger" distributed polymorphism, a simple sequence variant form of the enzyme having normal activity, rather than a "driver" disease-causing mutation that accounts for PSS. 28204496 0 11 theme sequence 152:159 arg1 polymorphisim 161:173 a simple sequence polymorphisim 143:173 a simple sequence polymorphisim 143:173 The glycan-specific sulfotransferase (R77W)GalNAc-4-ST1 putatively responsible for peeling skin syndrome has normal properties consistent with a simple sequence polymorphisim. 28204496 12 12 theme genomic 2157:2163 arg1 differences 2174:2184 newly-identified genomic sequence differences 2140:2184 newly-identified genomic sequence differences 2140:2184 This study presents an example for guiding biomedical research initiatives, as well as medical and personal/family perspectives, regarding newly-identified genomic sequence differences. 28204496 3 13 theme R77W 664:667 arg1 mutation 669:676 a disease-causing missense R77W mutation 637:676 a disease-causing missense R77W mutation yielding the genodermatosis peeling skin syndrome (PSS) 637:732 A recent whole-exome sequencing study identifies (c.229 C > T) in the GalNAc-4-ST1 glycosyltransferase (CHST8) as a disease-causing missense R77W mutation yielding the genodermatosis peeling skin syndrome (PSS) when homozygous. 28204496 6 14 theme condition 1067:1075 arg1 diagnosis 1036:1044 potential clinical and/or prenatal diagnosis 1001:1044 potential clinical and/or prenatal diagnosis of a harmful medical condition 1001:1075 Such an identification could point toward potential clinical and/or prenatal diagnosis of a harmful medical condition. 28204496 0 15 with consistent 127:136 arg1 polymorphisim 161:173 a simple sequence polymorphisim 143:173 a simple sequence polymorphisim 143:173 The glycan-specific sulfotransferase (R77W)GalNAc-4-ST1 putatively responsible for peeling skin syndrome has normal properties consistent with a simple sequence polymorphisim. 28204496 0 16 theme responsible 67:77 arg1 GalNAc-4-ST1 43:54 The glycan-specific sulfotransferase (R77W)GalNAc-4-ST1 0:54 The glycan-specific sulfotransferase (R77W)GalNAc-4-ST1 putatively responsible for peeling skin syndrome 0:103 The glycan-specific sulfotransferase (R77W)GalNAc-4-ST1 putatively responsible for peeling skin syndrome has normal properties consistent with a simple sequence polymorphisim. 28204496 5 17 theme GalNAc-4-ST1 844:855 arg1 activity 857:864 keratinocyte GalNAc-4-ST1 activity 831:864 keratinocyte GalNAc-4-ST1 activity 831:864 2012;99:202-208) cite this sequence change as reducing keratinocyte GalNAc-4-ST1 activity, thus decreasing glycosaminoglycan sulfation, as the mechanism for this blistering disorder. 28204496 6 18 theme harmful 1051:1057 arg1 condition 1067:1075 a harmful medical condition 1049:1075 a harmful medical condition 1049:1075 Such an identification could point toward potential clinical and/or prenatal diagnosis of a harmful medical condition. 28204496 10 19 theme GalNAc-4-ST1 1541:1552 arg1 loss-of-function 1521:1536 loss-of-function 1521:1536 loss-of-function of GalNAc-4-ST1 1521:1552 In addition, loss-of-function of GalNAc-4-ST1 primarily presents as reproductive system aberrations rather than skin effects. 28204496 0 20 theme peeling 83:89 arg1 syndrome 96:103 peeling skin syndrome 83:103 peeling skin syndrome 83:103 The glycan-specific sulfotransferase (R77W)GalNAc-4-ST1 putatively responsible for peeling skin syndrome has normal properties consistent with a simple sequence polymorphisim. 28204496 1 21 theme Expanded 176:183 arg1 access 185:190 Expanded access 176:190 Expanded access to DNA sequencing 176:208 Expanded access to DNA sequencing now fosters ready detection of site-specific human genome alterations whose actual significance requires in-depth functional study to rule in or out disease-causing mutations. 28204496 11 22 theme passenger 1824:1832 arg1 " 1833:1833 a "passenger" 1821:1833 a "passenger" distributed polymorphism, a simple sequence variant form of the enzyme having normal activity, rather than a "driver" disease-causing mutation that accounts for PSS 1821:1998 These findings, an allele frequency of 0.004357, and a 10-fold difference in prevalence of CHST8 (c.299 C > T, R77W) across different ethnic groups, suggest that this sequence represents a "passenger" distributed polymorphism, a simple sequence variant form of the enzyme having normal activity, rather than a "driver" disease-causing mutation that accounts for PSS. 28204496 10 23 dep system 1589:1594 arg1 aberrations 1596:1606 aberrations 1596:1606 reproductive system aberrations rather than skin effects 1576:1631 In addition, loss-of-function of GalNAc-4-ST1 primarily presents as reproductive system aberrations rather than skin effects. 28204496 6 24 theme prenatal 1027:1034 arg1 diagnosis 1036:1044 potential clinical and/or prenatal diagnosis 1001:1044 potential clinical and/or prenatal diagnosis of a harmful medical condition 1001:1075 Such an identification could point toward potential clinical and/or prenatal diagnosis of a harmful medical condition. 28204496 10 25 theme reproductive 1576:1587 arg1 system 1589:1594 reproductive system aberrations rather than skin effects 1576:1631 reproductive system aberrations rather than skin effects 1576:1631 In addition, loss-of-function of GalNAc-4-ST1 primarily presents as reproductive system aberrations rather than skin effects. 28204496 2 26 theme sequence 427:434 arg1 differences 436:446 genomic sequence differences 419:446 genomic sequence differences 419:446 This is a particular concern for genomic sequence differences in glycosyltransferases, whose implications are often difficult to assess. 28204496 0 27 theme normal 109:114 arg1 properties 116:125 normal properties 109:125 normal properties consistent with a simple sequence polymorphisim 109:173 The glycan-specific sulfotransferase (R77W)GalNAc-4-ST1 putatively responsible for peeling skin syndrome has normal properties consistent with a simple sequence polymorphisim. 28204496 3 28 dep identifies 561:570 arg1 T 583:583 c.229 C > T 573:583 c.229 C > T 573:583 A recent whole-exome sequencing study identifies (c.229 C > T) in the GalNAc-4-ST1 glycosyltransferase (CHST8) as a disease-causing missense R77W mutation yielding the genodermatosis peeling skin syndrome (PSS) when homozygous. 28204496 7 29 link β1,4-linked 1175:1185 arg1 GalNAc 1187:1192 terminal β1,4-linked GalNAc 1166:1192 terminal β1,4-linked GalNAc on N- and O-linked oligosaccharides on specific glycoproteins 1166:1254 However, GalNAc-4-ST1 has minimal activity toward glycosaminoglycans, instead modifying terminal β1,4-linked GalNAc on N- and O-linked oligosaccharides on specific glycoproteins. 28204496 0 30 theme sulfotransferase 20:35 arg1 GalNAc-4-ST1 43:54 The glycan-specific sulfotransferase (R77W)GalNAc-4-ST1 0:54 The glycan-specific sulfotransferase (R77W)GalNAc-4-ST1 putatively responsible for peeling skin syndrome 0:103 The glycan-specific sulfotransferase (R77W)GalNAc-4-ST1 putatively responsible for peeling skin syndrome has normal properties consistent with a simple sequence polymorphisim. 28204496 1 31 theme functional 324:333 arg1 study 335:339 in-depth functional study 315:339 in-depth functional study to rule in or out disease-causing mutations 315:383 Expanded access to DNA sequencing now fosters ready detection of site-specific human genome alterations whose actual significance requires in-depth functional study to rule in or out disease-causing mutations. 28204496 3 32 theme genodermatosis 691:704 arg1 PSS 729:731 PSS 729:731 PSS 729:731 A recent whole-exome sequencing study identifies (c.229 C > T) in the GalNAc-4-ST1 glycosyltransferase (CHST8) as a disease-causing missense R77W mutation yielding the genodermatosis peeling skin syndrome (PSS) when homozygous. 28204496 3 32 theme genodermatosis 691:704 arg1 syndrome 719:726 the genodermatosis peeling skin syndrome 687:726 the genodermatosis peeling skin syndrome (PSS) 687:732 A recent whole-exome sequencing study identifies (c.229 C > T) in the GalNAc-4-ST1 glycosyltransferase (CHST8) as a disease-causing missense R77W mutation yielding the genodermatosis peeling skin syndrome (PSS) when homozygous. 28204496 0 33 theme R77W 38:41 arg1 GalNAc-4-ST1 43:54 The glycan-specific sulfotransferase (R77W)GalNAc-4-ST1 0:54 The glycan-specific sulfotransferase (R77W)GalNAc-4-ST1 putatively responsible for peeling skin syndrome 0:103 The glycan-specific sulfotransferase (R77W)GalNAc-4-ST1 putatively responsible for peeling skin syndrome has normal properties consistent with a simple sequence polymorphisim. 28204496 7 34 from GalNAc 1187:1192 arg1 oligosaccharides 1213:1228 O-linked oligosaccharides 1204:1228 O-linked oligosaccharides 1204:1228 However, GalNAc-4-ST1 has minimal activity toward glycosaminoglycans, instead modifying terminal β1,4-linked GalNAc on N- and O-linked oligosaccharides on specific glycoproteins. 28204496 7 34 from GalNAc 1187:1192 arg1 N- 1197:1198 N- 1197:1198 N- 1197:1198 However, GalNAc-4-ST1 has minimal activity toward glycosaminoglycans, instead modifying terminal β1,4-linked GalNAc on N- and O-linked oligosaccharides on specific glycoproteins. 28204496 11 35 theme different 1758:1766 arg1 groups 1775:1780 different ethnic groups 1758:1780 different ethnic groups 1758:1780 These findings, an allele frequency of 0.004357, and a 10-fold difference in prevalence of CHST8 (c.299 C > T, R77W) across different ethnic groups, suggest that this sequence represents a "passenger" distributed polymorphism, a simple sequence variant form of the enzyme having normal activity, rather than a "driver" disease-causing mutation that accounts for PSS. 28204496 3 36 theme whole-exome 532:542 arg1 study 555:559 A recent whole-exome sequencing study 523:559 A recent whole-exome sequencing study 523:559 A recent whole-exome sequencing study identifies (c.229 C > T) in the GalNAc-4-ST1 glycosyltransferase (CHST8) as a disease-causing missense R77W mutation yielding the genodermatosis peeling skin syndrome (PSS) when homozygous. 28204496 7 37 theme O-linked 1204:1211 arg1 oligosaccharides 1213:1228 O-linked oligosaccharides 1204:1228 O-linked oligosaccharides 1204:1228 However, GalNAc-4-ST1 has minimal activity toward glycosaminoglycans, instead modifying terminal β1,4-linked GalNAc on N- and O-linked oligosaccharides on specific glycoproteins. 28204496 7 38 theme terminal 1166:1173 arg1 GalNAc 1187:1192 terminal β1,4-linked GalNAc 1166:1192 terminal β1,4-linked GalNAc on N- and O-linked oligosaccharides on specific glycoproteins 1166:1254 However, GalNAc-4-ST1 has minimal activity toward glycosaminoglycans, instead modifying terminal β1,4-linked GalNAc on N- and O-linked oligosaccharides on specific glycoproteins. 28204496 7 39 from N- 1197:1198 arg1 glycoproteins 1242:1254 specific glycoproteins 1233:1254 specific glycoproteins 1233:1254 However, GalNAc-4-ST1 has minimal activity toward glycosaminoglycans, instead modifying terminal β1,4-linked GalNAc on N- and O-linked oligosaccharides on specific glycoproteins. 28204496 0 40 contain has 105:107 arg2 properties 116:125 normal properties 109:125 normal properties consistent with a simple sequence polymorphisim 109:173 The glycan-specific sulfotransferase (R77W)GalNAc-4-ST1 putatively responsible for peeling skin syndrome has normal properties consistent with a simple sequence polymorphisim. 28204496 0 40 contain has 105:107 arg1 GalNAc-4-ST1 43:54 The glycan-specific sulfotransferase (R77W)GalNAc-4-ST1 0:54 The glycan-specific sulfotransferase (R77W)GalNAc-4-ST1 putatively responsible for peeling skin syndrome 0:103 The glycan-specific sulfotransferase (R77W)GalNAc-4-ST1 putatively responsible for peeling skin syndrome has normal properties consistent with a simple sequence polymorphisim. 28204496 11 41 theme enzyme 1899:1904 arg1 form 1887:1890 a simple sequence variant form 1861:1890 a simple sequence variant form of the enzyme having normal activity 1861:1927 These findings, an allele frequency of 0.004357, and a 10-fold difference in prevalence of CHST8 (c.299 C > T, R77W) across different ethnic groups, suggest that this sequence represents a "passenger" distributed polymorphism, a simple sequence variant form of the enzyme having normal activity, rather than a "driver" disease-causing mutation that accounts for PSS. 28204496 11 41 theme enzyme 1899:1904 arg1 polymorphism 1847:1858 polymorphism 1847:1858 polymorphism 1847:1858 These findings, an allele frequency of 0.004357, and a 10-fold difference in prevalence of CHST8 (c.299 C > T, R77W) across different ethnic groups, suggest that this sequence represents a "passenger" distributed polymorphism, a simple sequence variant form of the enzyme having normal activity, rather than a "driver" disease-causing mutation that accounts for PSS. 28204496 3 42 theme skin 714:717 arg1 PSS 729:731 PSS 729:731 PSS 729:731 A recent whole-exome sequencing study identifies (c.229 C > T) in the GalNAc-4-ST1 glycosyltransferase (CHST8) as a disease-causing missense R77W mutation yielding the genodermatosis peeling skin syndrome (PSS) when homozygous. 28204496 3 42 theme skin 714:717 arg1 syndrome 719:726 the genodermatosis peeling skin syndrome 687:726 the genodermatosis peeling skin syndrome (PSS) 687:732 A recent whole-exome sequencing study identifies (c.229 C > T) in the GalNAc-4-ST1 glycosyltransferase (CHST8) as a disease-causing missense R77W mutation yielding the genodermatosis peeling skin syndrome (PSS) when homozygous. 28204496 7 43 gly glycoproteins 1242:1254 arg1 glycoproteins 1242:1254 specific glycoproteins 1233:1254 specific glycoproteins 1233:1254 However, GalNAc-4-ST1 has minimal activity toward glycosaminoglycans, instead modifying terminal β1,4-linked GalNAc on N- and O-linked oligosaccharides on specific glycoproteins. 28204496 11 44 theme CHST8 1725:1729 arg1 prevalence 1711:1720 prevalence 1711:1720 prevalence of CHST8 (c.299 C > T, R77W) across different ethnic groups 1711:1780 These findings, an allele frequency of 0.004357, and a 10-fold difference in prevalence of CHST8 (c.299 C > T, R77W) across different ethnic groups, suggest that this sequence represents a "passenger" distributed polymorphism, a simple sequence variant form of the enzyme having normal activity, rather than a "driver" disease-causing mutation that accounts for PSS. 28204496 2 45 theme particular 396:405 arg1 concern 407:413 a particular concern 394:413 a particular concern for genomic sequence differences in glycosyltransferases, whose implications are often difficult to assess 394:520 This is a particular concern for genomic sequence differences in glycosyltransferases, whose implications are often difficult to assess. 28204496 2 45 theme particular 396:405 arg1 This 386:389 This 386:389 This 386:389 This is a particular concern for genomic sequence differences in glycosyltransferases, whose implications are often difficult to assess. 28204496 1 46 theme human 255:259 arg1 alterations 268:278 site-specific human genome alterations 241:278 site-specific human genome alterations 241:278 Expanded access to DNA sequencing now fosters ready detection of site-specific human genome alterations whose actual significance requires in-depth functional study to rule in or out disease-causing mutations. 28204496 1 47 theme alterations 268:278 arg1 detection 228:236 ready detection 222:236 ready detection of site-specific human genome alterations whose actual significance requires in-depth functional study to rule in or out disease-causing mutations 222:383 Expanded access to DNA sequencing now fosters ready detection of site-specific human genome alterations whose actual significance requires in-depth functional study to rule in or out disease-causing mutations. 28204496 7 48 theme β1,4-linked 1175:1185 arg1 GalNAc 1187:1192 terminal β1,4-linked GalNAc 1166:1192 terminal β1,4-linked GalNAc on N- and O-linked oligosaccharides on specific glycoproteins 1166:1254 However, GalNAc-4-ST1 has minimal activity toward glycosaminoglycans, instead modifying terminal β1,4-linked GalNAc on N- and O-linked oligosaccharides on specific glycoproteins. 28204496 11 49 theme allele 1653:1658 arg1 frequency 1660:1668 an allele frequency 1650:1668 an allele frequency of 0.004357 1650:1680 These findings, an allele frequency of 0.004357, and a 10-fold difference in prevalence of CHST8 (c.299 C > T, R77W) across different ethnic groups, suggest that this sequence represents a "passenger" distributed polymorphism, a simple sequence variant form of the enzyme having normal activity, rather than a "driver" disease-causing mutation that accounts for PSS. 28204496 1 50 theme actual 286:291 arg1 significance 293:304 significance 293:304 significance 293:304 Expanded access to DNA sequencing now fosters ready detection of site-specific human genome alterations whose actual significance requires in-depth functional study to rule in or out disease-causing mutations. 28204496 11 51 theme normal 1913:1918 arg1 activity 1920:1927 normal activity 1913:1927 normal activity 1913:1927 These findings, an allele frequency of 0.004357, and a 10-fold difference in prevalence of CHST8 (c.299 C > T, R77W) across different ethnic groups, suggest that this sequence represents a "passenger" distributed polymorphism, a simple sequence variant form of the enzyme having normal activity, rather than a "driver" disease-causing mutation that accounts for PSS. 28204496 3 52 theme C 579:579 arg1 T 583:583 c.229 C > T 573:583 c.229 C > T 573:583 A recent whole-exome sequencing study identifies (c.229 C > T) in the GalNAc-4-ST1 glycosyltransferase (CHST8) as a disease-causing missense R77W mutation yielding the genodermatosis peeling skin syndrome (PSS) when homozygous. 28204496 5 53 theme glycosaminoglycan 883:899 arg1 sulfation 901:909 glycosaminoglycan sulfation 883:909 glycosaminoglycan sulfation 883:909 2012;99:202-208) cite this sequence change as reducing keratinocyte GalNAc-4-ST1 activity, thus decreasing glycosaminoglycan sulfation, as the mechanism for this blistering disorder. 28204496 5 53 theme glycosaminoglycan 883:899 arg1 mechanism 919:927 the mechanism 915:927 the mechanism for this blistering disorder 915:956 2012;99:202-208) cite this sequence change as reducing keratinocyte GalNAc-4-ST1 activity, thus decreasing glycosaminoglycan sulfation, as the mechanism for this blistering disorder. 28204496 12 54 theme research 2055:2062 arg1 initiatives 2064:2074 biomedical research initiatives 2044:2074 biomedical research initiatives 2044:2074 This study presents an example for guiding biomedical research initiatives, as well as medical and personal/family perspectives, regarding newly-identified genomic sequence differences. 28204496 8 55 theme GalNAc-4-ST1 1314:1325 arg1 processing 1277:1286 processing 1277:1286 processing 1277:1286 We find expression, processing and catalytic activity of GalNAc-4-ST1 completely equivalent between wild type and (R77W) sulfotransferases. 28204496 8 55 theme GalNAc-4-ST1 1314:1325 arg1 activity 1302:1309 catalytic activity 1292:1309 catalytic activity of GalNAc-4-ST1 completely equivalent between wild type and (R77W) sulfotransferases 1292:1394 We find expression, processing and catalytic activity of GalNAc-4-ST1 completely equivalent between wild type and (R77W) sulfotransferases. 28204496 8 55 theme GalNAc-4-ST1 1314:1325 arg1 expression 1265:1274 expression 1265:1274 expression 1265:1274 We find expression, processing and catalytic activity of GalNAc-4-ST1 completely equivalent between wild type and (R77W) sulfotransferases. 28204496 3 56 theme GalNAc-4-ST1 593:604 arg1 CHST8 627:631 CHST8 627:631 CHST8 627:631 A recent whole-exome sequencing study identifies (c.229 C > T) in the GalNAc-4-ST1 glycosyltransferase (CHST8) as a disease-causing missense R77W mutation yielding the genodermatosis peeling skin syndrome (PSS) when homozygous. 28204496 3 56 theme GalNAc-4-ST1 593:604 arg1 glycosyltransferase 606:624 the GalNAc-4-ST1 glycosyltransferase 589:624 the GalNAc-4-ST1 glycosyltransferase (CHST8) 589:632 A recent whole-exome sequencing study identifies (c.229 C > T) in the GalNAc-4-ST1 glycosyltransferase (CHST8) as a disease-causing missense R77W mutation yielding the genodermatosis peeling skin syndrome (PSS) when homozygous. 28204496 1 57 theme DNA 195:197 arg1 sequencing 199:208 DNA sequencing 195:208 DNA sequencing 195:208 Expanded access to DNA sequencing now fosters ready detection of site-specific human genome alterations whose actual significance requires in-depth functional study to rule in or out disease-causing mutations. 28204496 9 58 dep little 1426:1431 arg1 mRNA 1452:1455 GalNAc-4-ST1 mRNA 1439:1455 GalNAc-4-ST1 mRNA 1439:1455 Moreover, keratinocytes have little or no GalNAc-4-ST1 mRNA, indicating that they do not express GalNAc-4-ST1. 28204496 8 59 theme equivalent 1338:1347 arg1 activity 1302:1309 catalytic activity 1292:1309 catalytic activity of GalNAc-4-ST1 completely equivalent between wild type and (R77W) sulfotransferases 1292:1394 We find expression, processing and catalytic activity of GalNAc-4-ST1 completely equivalent between wild type and (R77W) sulfotransferases. 28204496 11 60 theme sequence 1870:1877 arg1 form 1887:1890 a simple sequence variant form 1861:1890 a simple sequence variant form of the enzyme having normal activity 1861:1927 These findings, an allele frequency of 0.004357, and a 10-fold difference in prevalence of CHST8 (c.299 C > T, R77W) across different ethnic groups, suggest that this sequence represents a "passenger" distributed polymorphism, a simple sequence variant form of the enzyme having normal activity, rather than a "driver" disease-causing mutation that accounts for PSS. 28204496 11 60 theme sequence 1870:1877 arg1 polymorphism 1847:1858 polymorphism 1847:1858 polymorphism 1847:1858 These findings, an allele frequency of 0.004357, and a 10-fold difference in prevalence of CHST8 (c.299 C > T, R77W) across different ethnic groups, suggest that this sequence represents a "passenger" distributed polymorphism, a simple sequence variant form of the enzyme having normal activity, rather than a "driver" disease-causing mutation that accounts for PSS. 28204496 6 61 theme potential 1001:1009 arg1 diagnosis 1036:1044 potential clinical and/or prenatal diagnosis 1001:1044 potential clinical and/or prenatal diagnosis of a harmful medical condition 1001:1075 Such an identification could point toward potential clinical and/or prenatal diagnosis of a harmful medical condition. 28204496 8 62 theme wild 1357:1360 arg1 type 1362:1365 wild type 1357:1365 wild type 1357:1365 We find expression, processing and catalytic activity of GalNAc-4-ST1 completely equivalent between wild type and (R77W) sulfotransferases. 28204496 7 63 theme minimal 1104:1110 arg1 activity 1112:1119 minimal activity 1104:1119 minimal activity toward glycosaminoglycans 1104:1145 However, GalNAc-4-ST1 has minimal activity toward glycosaminoglycans, instead modifying terminal β1,4-linked GalNAc on N- and O-linked oligosaccharides on specific glycoproteins. 28204496 1 64 theme ready 222:226 arg1 detection 228:236 ready detection 222:236 ready detection of site-specific human genome alterations whose actual significance requires in-depth functional study to rule in or out disease-causing mutations 222:383 Expanded access to DNA sequencing now fosters ready detection of site-specific human genome alterations whose actual significance requires in-depth functional study to rule in or out disease-causing mutations. 28204496 5 65 theme blistering 938:947 arg1 disorder 949:956 this blistering disorder 933:956 this blistering disorder 933:956 2012;99:202-208) cite this sequence change as reducing keratinocyte GalNAc-4-ST1 activity, thus decreasing glycosaminoglycan sulfation, as the mechanism for this blistering disorder. 28204496 6 66 dep potential 1001:1009 arg1 clinical 1011:1018 clinical 1011:1018 clinical 1011:1018 Such an identification could point toward potential clinical and/or prenatal diagnosis of a harmful medical condition. 28204496 8 67 theme R77W 1372:1375 arg1 sulfotransferases 1378:1394 (R77W) sulfotransferases 1371:1394 (R77W) sulfotransferases 1371:1394 We find expression, processing and catalytic activity of GalNAc-4-ST1 completely equivalent between wild type and (R77W) sulfotransferases. 28204496 7 68 theme specific 1233:1240 arg1 glycoproteins 1242:1254 specific glycoproteins 1233:1254 specific glycoproteins 1233:1254 However, GalNAc-4-ST1 has minimal activity toward glycosaminoglycans, instead modifying terminal β1,4-linked GalNAc on N- and O-linked oligosaccharides on specific glycoproteins. 28204496 3 69 theme missense 655:662 arg1 mutation 669:676 a disease-causing missense R77W mutation 637:676 a disease-causing missense R77W mutation yielding the genodermatosis peeling skin syndrome (PSS) 637:732 A recent whole-exome sequencing study identifies (c.229 C > T) in the GalNAc-4-ST1 glycosyltransferase (CHST8) as a disease-causing missense R77W mutation yielding the genodermatosis peeling skin syndrome (PSS) when homozygous. 28204496 12 70 theme newly-identified 2140:2155 arg1 differences 2174:2184 newly-identified genomic sequence differences 2140:2184 newly-identified genomic sequence differences 2140:2184 This study presents an example for guiding biomedical research initiatives, as well as medical and personal/family perspectives, regarding newly-identified genomic sequence differences. 28204496 11 71 from findings 1640:1647 arg1 prevalence 1711:1720 prevalence 1711:1720 prevalence of CHST8 (c.299 C > T, R77W) across different ethnic groups 1711:1780 These findings, an allele frequency of 0.004357, and a 10-fold difference in prevalence of CHST8 (c.299 C > T, R77W) across different ethnic groups, suggest that this sequence represents a "passenger" distributed polymorphism, a simple sequence variant form of the enzyme having normal activity, rather than a "driver" disease-causing mutation that accounts for PSS. 28204496 6 72 theme medical 1059:1065 arg1 condition 1067:1075 a harmful medical condition 1049:1075 a harmful medical condition 1049:1075 Such an identification could point toward potential clinical and/or prenatal diagnosis of a harmful medical condition. 28204496 12 73 theme medical 2088:2094 arg1 perspectives 2116:2127 medical and personal/family perspectives 2088:2127 medical and personal/family perspectives 2088:2127 This study presents an example for guiding biomedical research initiatives, as well as medical and personal/family perspectives, regarding newly-identified genomic sequence differences. 28204496 0 74 theme skin 91:94 arg1 syndrome 96:103 peeling skin syndrome 83:103 peeling skin syndrome 83:103 The glycan-specific sulfotransferase (R77W)GalNAc-4-ST1 putatively responsible for peeling skin syndrome has normal properties consistent with a simple sequence polymorphisim. 28204496 1 75 theme disease-causing 359:373 arg1 mutations 375:383 disease-causing mutations 359:383 disease-causing mutations 359:383 Expanded access to DNA sequencing now fosters ready detection of site-specific human genome alterations whose actual significance requires in-depth functional study to rule in or out disease-causing mutations. 28204496 3 76 theme disease-causing 639:653 arg1 mutation 669:676 a disease-causing missense R77W mutation 637:676 a disease-causing missense R77W mutation yielding the genodermatosis peeling skin syndrome (PSS) 637:732 A recent whole-exome sequencing study identifies (c.229 C > T) in the GalNAc-4-ST1 glycosyltransferase (CHST8) as a disease-causing missense R77W mutation yielding the genodermatosis peeling skin syndrome (PSS) when homozygous. 28204496 7 77 from oligosaccharides 1213:1228 arg1 glycoproteins 1242:1254 specific glycoproteins 1233:1254 specific glycoproteins 1233:1254 However, GalNAc-4-ST1 has minimal activity toward glycosaminoglycans, instead modifying terminal β1,4-linked GalNAc on N- and O-linked oligosaccharides on specific glycoproteins. 28204496 12 78 theme personal/family 2100:2114 arg1 perspectives 2116:2127 medical and personal/family perspectives 2088:2127 medical and personal/family perspectives 2088:2127 This study presents an example for guiding biomedical research initiatives, as well as medical and personal/family perspectives, regarding newly-identified genomic sequence differences. 28204496 12 79 theme sequence 2165:2172 arg1 differences 2174:2184 newly-identified genomic sequence differences 2140:2184 newly-identified genomic sequence differences 2140:2184 This study presents an example for guiding biomedical research initiatives, as well as medical and personal/family perspectives, regarding newly-identified genomic sequence differences. 28204496 7 80 contain has 1100:1102 arg1 GalNAc-4-ST1 1087:1098 GalNAc-4-ST1 1087:1098 GalNAc-4-ST1 1087:1098 However, GalNAc-4-ST1 has minimal activity toward glycosaminoglycans, instead modifying terminal β1,4-linked GalNAc on N- and O-linked oligosaccharides on specific glycoproteins. 28204496 7 80 contain has 1100:1102 arg2 activity 1112:1119 minimal activity 1104:1119 minimal activity toward glycosaminoglycans 1104:1145 However, GalNAc-4-ST1 has minimal activity toward glycosaminoglycans, instead modifying terminal β1,4-linked GalNAc on N- and O-linked oligosaccharides on specific glycoproteins. 28204496 2 81 theme genomic 419:425 arg1 differences 436:446 genomic sequence differences 419:446 genomic sequence differences 419:446 This is a particular concern for genomic sequence differences in glycosyltransferases, whose implications are often difficult to assess. 28204496 0 82 theme glycan-specific 4:18 arg1 GalNAc-4-ST1 43:54 The glycan-specific sulfotransferase (R77W)GalNAc-4-ST1 0:54 The glycan-specific sulfotransferase (R77W)GalNAc-4-ST1 putatively responsible for peeling skin syndrome 0:103 The glycan-specific sulfotransferase (R77W)GalNAc-4-ST1 putatively responsible for peeling skin syndrome has normal properties consistent with a simple sequence polymorphisim. 28204496 0 83 theme simple 145:150 arg1 polymorphisim 161:173 a simple sequence polymorphisim 143:173 a simple sequence polymorphisim 143:173 The glycan-specific sulfotransferase (R77W)GalNAc-4-ST1 putatively responsible for peeling skin syndrome has normal properties consistent with a simple sequence polymorphisim. 28204496 1 84 dep mutations 375:383 arg1 out 355:357 out 355:357 out 355:357 Expanded access to DNA sequencing now fosters ready detection of site-specific human genome alterations whose actual significance requires in-depth functional study to rule in or out disease-causing mutations. 28204496 9 85 contain have 1421:1424 arg2 little 1426:1431 little 1426:1431 little 1426:1431 Moreover, keratinocytes have little or no GalNAc-4-ST1 mRNA, indicating that they do not express GalNAc-4-ST1. 28204496 9 85 contain have 1421:1424 arg1 keratinocytes 1407:1419 keratinocytes 1407:1419 keratinocytes 1407:1419 Moreover, keratinocytes have little or no GalNAc-4-ST1 mRNA, indicating that they do not express GalNAc-4-ST1. 28204496 9 85 contain have 1421:1424 arg2 no 1436:1437 no 1436:1437 no 1436:1437 Moreover, keratinocytes have little or no GalNAc-4-ST1 mRNA, indicating that they do not express GalNAc-4-ST1. 28204496 10 86 attach presents 1564:1571 arg2 loss-of-function 1521:1536 loss-of-function 1521:1536 loss-of-function of GalNAc-4-ST1 1521:1552 In addition, loss-of-function of GalNAc-4-ST1 primarily presents as reproductive system aberrations rather than skin effects. 28204496 10 86 attach presents 1564:1571 arg1 addition 1511:1518 addition 1511:1518 addition 1511:1518 In addition, loss-of-function of GalNAc-4-ST1 primarily presents as reproductive system aberrations rather than skin effects. 28204496 5 87 theme keratinocyte 831:842 arg1 activity 857:864 keratinocyte GalNAc-4-ST1 activity 831:864 keratinocyte GalNAc-4-ST1 activity 831:864 2012;99:202-208) cite this sequence change as reducing keratinocyte GalNAc-4-ST1 activity, thus decreasing glycosaminoglycan sulfation, as the mechanism for this blistering disorder. 28204496 1 88 theme in-depth 315:322 arg1 study 335:339 in-depth functional study 315:339 in-depth functional study to rule in or out disease-causing mutations 315:383 Expanded access to DNA sequencing now fosters ready detection of site-specific human genome alterations whose actual significance requires in-depth functional study to rule in or out disease-causing mutations. 28204496 4 89 dep Cabral 751:756 arg1 Genomics 766:773 Genomics 766:773 Genomics 766:773 Cabral et al. (Genomics. 28204496 4 89 dep Cabral 751:756 arg1 al 761:762 Cabral et al 751:762 Cabral et al. 751:763 Cabral et al. (Genomics. 28204496 11 90 theme ethnic 1768:1773 arg1 groups 1775:1780 different ethnic groups 1758:1780 different ethnic groups 1758:1780 These findings, an allele frequency of 0.004357, and a 10-fold difference in prevalence of CHST8 (c.299 C > T, R77W) across different ethnic groups, suggest that this sequence represents a "passenger" distributed polymorphism, a simple sequence variant form of the enzyme having normal activity, rather than a "driver" disease-causing mutation that accounts for PSS. 28204496 9 91 theme GalNAc-4-ST1 1439:1450 arg1 mRNA 1452:1455 GalNAc-4-ST1 mRNA 1439:1455 GalNAc-4-ST1 mRNA 1439:1455 Moreover, keratinocytes have little or no GalNAc-4-ST1 mRNA, indicating that they do not express GalNAc-4-ST1. 28204496 11 92 theme " 1951:1951 arg1 mutation 1969:1976 a "driver" disease-causing mutation 1942:1976 polymorphism, a simple sequence variant form of the enzyme having normal activity, rather than a "driver" disease-causing mutation that accounts for PSS 1847:1998 These findings, an allele frequency of 0.004357, and a 10-fold difference in prevalence of CHST8 (c.299 C > T, R77W) across different ethnic groups, suggest that this sequence represents a "passenger" distributed polymorphism, a simple sequence variant form of the enzyme having normal activity, rather than a "driver" disease-causing mutation that accounts for PSS. 28204496 11 93 theme 10-fold 1689:1695 arg1 difference 1697:1706 a 10-fold difference 1687:1706 a 10-fold difference in prevalence of CHST8 (c.299 C > T, R77W) across different ethnic groups 1687:1780 These findings, an allele frequency of 0.004357, and a 10-fold difference in prevalence of CHST8 (c.299 C > T, R77W) across different ethnic groups, suggest that this sequence represents a "passenger" distributed polymorphism, a simple sequence variant form of the enzyme having normal activity, rather than a "driver" disease-causing mutation that accounts for PSS. 28204496 5 94 theme sequence 803:810 arg1 change 812:817 this sequence change 798:817 this sequence change 798:817 2012;99:202-208) cite this sequence change as reducing keratinocyte GalNAc-4-ST1 activity, thus decreasing glycosaminoglycan sulfation, as the mechanism for this blistering disorder. 28204496 11 95 contain having 1906:1911 arg1 enzyme 1899:1904 the enzyme 1895:1904 the enzyme having normal activity 1895:1927 These findings, an allele frequency of 0.004357, and a 10-fold difference in prevalence of CHST8 (c.299 C > T, R77W) across different ethnic groups, suggest that this sequence represents a "passenger" distributed polymorphism, a simple sequence variant form of the enzyme having normal activity, rather than a "driver" disease-causing mutation that accounts for PSS. 28204496 11 95 contain having 1906:1911 arg2 activity 1920:1927 normal activity 1913:1927 normal activity 1913:1927 These findings, an allele frequency of 0.004357, and a 10-fold difference in prevalence of CHST8 (c.299 C > T, R77W) across different ethnic groups, suggest that this sequence represents a "passenger" distributed polymorphism, a simple sequence variant form of the enzyme having normal activity, rather than a "driver" disease-causing mutation that accounts for PSS. 28204496 3 96 theme sequencing 544:553 arg1 study 555:559 A recent whole-exome sequencing study 523:559 A recent whole-exome sequencing study 523:559 A recent whole-exome sequencing study identifies (c.229 C > T) in the GalNAc-4-ST1 glycosyltransferase (CHST8) as a disease-causing missense R77W mutation yielding the genodermatosis peeling skin syndrome (PSS) when homozygous. 28204496 10 97 theme skin 1620:1623 arg1 effects 1625:1631 skin effects 1620:1631 reproductive system aberrations rather than skin effects 1576:1631 In addition, loss-of-function of GalNAc-4-ST1 primarily presents as reproductive system aberrations rather than skin effects. 28204496 3 98 theme peeling 706:712 arg1 PSS 729:731 PSS 729:731 PSS 729:731 A recent whole-exome sequencing study identifies (c.229 C > T) in the GalNAc-4-ST1 glycosyltransferase (CHST8) as a disease-causing missense R77W mutation yielding the genodermatosis peeling skin syndrome (PSS) when homozygous. 28204496 3 98 theme peeling 706:712 arg1 syndrome 719:726 the genodermatosis peeling skin syndrome 687:726 the genodermatosis peeling skin syndrome (PSS) 687:732 A recent whole-exome sequencing study identifies (c.229 C > T) in the GalNAc-4-ST1 glycosyltransferase (CHST8) as a disease-causing missense R77W mutation yielding the genodermatosis peeling skin syndrome (PSS) when homozygous. 28204496 3 99 theme recent 525:530 arg1 study 555:559 A recent whole-exome sequencing study 523:559 A recent whole-exome sequencing study 523:559 A recent whole-exome sequencing study identifies (c.229 C > T) in the GalNAc-4-ST1 glycosyltransferase (CHST8) as a disease-causing missense R77W mutation yielding the genodermatosis peeling skin syndrome (PSS) when homozygous. 28204496 1 100 theme site-specific 241:253 arg1 alterations 268:278 site-specific human genome alterations 241:278 site-specific human genome alterations 241:278 Expanded access to DNA sequencing now fosters ready detection of site-specific human genome alterations whose actual significance requires in-depth functional study to rule in or out disease-causing mutations. 28204496 2 101 from differences 436:446 arg1 glycosyltransferases 451:470 glycosyltransferases 451:470 glycosyltransferases 451:470 This is a particular concern for genomic sequence differences in glycosyltransferases, whose implications are often difficult to assess. 28204496 11 102 theme disease-causing 1953:1967 arg1 mutation 1969:1976 a "driver" disease-causing mutation 1942:1976 polymorphism, a simple sequence variant form of the enzyme having normal activity, rather than a "driver" disease-causing mutation that accounts for PSS 1847:1998 These findings, an allele frequency of 0.004357, and a 10-fold difference in prevalence of CHST8 (c.299 C > T, R77W) across different ethnic groups, suggest that this sequence represents a "passenger" distributed polymorphism, a simple sequence variant form of the enzyme having normal activity, rather than a "driver" disease-causing mutation that accounts for PSS. 28204496 1 103 theme genome 261:266 arg1 alterations 268:278 site-specific human genome alterations 241:278 site-specific human genome alterations 241:278 Expanded access to DNA sequencing now fosters ready detection of site-specific human genome alterations whose actual significance requires in-depth functional study to rule in or out disease-causing mutations. 28012129 12 0 from cells 1478:1482 arg1 vicinity 1493:1500 close vicinity 1487:1500 close vicinity to extracellular trophoblasts 1487:1530 Co-localization of CD24 with Siglec-10 was observed in endometrial glands and in first trimester decidual cells in close vicinity to extracellular trophoblasts. 28012129 12 1 theme decidual 1469:1476 arg1 cells 1478:1482 first trimester decidual cells 1453:1482 first trimester decidual cells in close vicinity to extracellular trophoblasts 1453:1530 Co-localization of CD24 with Siglec-10 was observed in endometrial glands and in first trimester decidual cells in close vicinity to extracellular trophoblasts. 28012129 8 2 theme EDTA-sensitive 979:992 arg1 interaction 1009:1019 EDTA-sensitive CD24-Siglec-10 interaction 979:1019 EDTA-sensitive CD24-Siglec-10 interaction via the terminal sialic acid glycan residues of CD24 979:1072 EDTA-sensitive CD24-Siglec-10 interaction via the terminal sialic acid glycan residues of CD24 was observed. 28012129 3 3 theme suppression 501:511 arg1 response 513:520 the immune suppression response 490:520 the immune suppression response in the placenta 490:536 This interaction was assessed as a candidate complex for the immune suppression response in the placenta. 28012129 7 4 with consistent 913:922 arg1 degree 938:943 its high degree 929:943 its high degree of N- and O-linked glycosylation 929:976 Placental CD24 had an apparent molecular weight of 30-70 kDa consistent with its high degree of N- and O-linked glycosylation. 28012129 5 5 theme Siglecs 663:669 arg1 Binding 640:646 Binding 640:646 Binding of recombinant Siglecs to placental CD24 640:687 Binding of recombinant Siglecs to placental CD24 was evaluated by ELISA. 28012129 3 6 from response 513:520 arg1 placenta 529:536 the placenta 525:536 the placenta 525:536 This interaction was assessed as a candidate complex for the immune suppression response in the placenta. 28012129 7 7 theme apparent 874:881 arg1 weight 893:898 an apparent molecular weight 871:898 an apparent molecular weight of 30-70 kDa consistent with its high degree of N- and O-linked glycosylation 871:976 Placental CD24 had an apparent molecular weight of 30-70 kDa consistent with its high degree of N- and O-linked glycosylation. 28012129 14 8 theme interactions 1752:1763 arg1 regions 1726:1732 these regions 1720:1732 these regions of fetal-maternal interactions 1720:1763 The presence of the CD24-Siglec-10 in these regions of fetal-maternal interactions suggests a possible role in mediating immune tolerance at the fetal-maternal interface. 28012129 12 9 with Co-localization 1372:1386 arg1 Siglec-10 1401:1409 Siglec-10 1401:1409 Siglec-10 1401:1409 Co-localization of CD24 with Siglec-10 was observed in endometrial glands and in first trimester decidual cells in close vicinity to extracellular trophoblasts. 28012129 14 10 theme possible 1776:1783 arg1 role 1785:1788 a possible role 1774:1788 a possible role 1774:1788 The presence of the CD24-Siglec-10 in these regions of fetal-maternal interactions suggests a possible role in mediating immune tolerance at the fetal-maternal interface. 28012129 13 11 theme placental 1639:1647 arg1 layers 1631:1636 the placenta cytotrophoblast layers 1602:1636 the placenta cytotrophoblast layers 1602:1636 This study is the first to demonstrate the early presence of CD24 in the placenta cytotrophoblast layers, placental bed and maternal uterine glands. 28012129 13 11 theme placental 1639:1647 arg1 bed 1649:1651 placental bed 1639:1651 placental bed 1639:1651 This study is the first to demonstrate the early presence of CD24 in the placenta cytotrophoblast layers, placental bed and maternal uterine glands. 28012129 12 12 theme first 1453:1457 arg1 cells 1478:1482 first trimester decidual cells 1453:1482 first trimester decidual cells in close vicinity to extracellular trophoblasts 1453:1530 Co-localization of CD24 with Siglec-10 was observed in endometrial glands and in first trimester decidual cells in close vicinity to extracellular trophoblasts. 28012129 8 13 theme sialic 1038:1043 arg1 CD24 1069:1072 CD24 1069:1072 CD24 1069:1072 EDTA-sensitive CD24-Siglec-10 interaction via the terminal sialic acid glycan residues of CD24 was observed. 28012129 8 13 theme sialic 1038:1043 arg1 residues 1057:1064 the terminal sialic acid glycan residues 1025:1064 the terminal sialic acid glycan residues of CD24 1025:1072 EDTA-sensitive CD24-Siglec-10 interaction via the terminal sialic acid glycan residues of CD24 was observed. 28012129 2 14 gly glycoprotein 258:269 arg1 CD24 239:242 CD24 239:242 CD24 239:242 CD24, a mucin-like glycoprotein expressed at the surface of hematopoietic cells and diverse tumor cells, is known to interact with the sialic acid-binding immunoglobulin-type lectins (Siglecs). 28012129 2 14 gly glycoprotein 258:269 arg1 glycoprotein 258:269 a mucin-like glycoprotein 245:269 a mucin-like glycoprotein expressed at the surface of hematopoietic cells and diverse tumor cells 245:341 CD24, a mucin-like glycoprotein expressed at the surface of hematopoietic cells and diverse tumor cells, is known to interact with the sialic acid-binding immunoglobulin-type lectins (Siglecs). 28012129 6 15 theme placental 769:777 arg1 tissues 779:785 first trimester placental tissues 753:785 first trimester placental tissues 753:785 The expression of CD24 and Siglec-10 in first trimester placental tissues was investigated by immunohistochemistry and immunofluorescence. 28012129 2 16 theme cells 313:317 arg1 surface 288:294 the surface 284:294 the surface of hematopoietic cells and diverse tumor cells 284:341 CD24, a mucin-like glycoprotein expressed at the surface of hematopoietic cells and diverse tumor cells, is known to interact with the sialic acid-binding immunoglobulin-type lectins (Siglecs). 28012129 7 17 theme Placental 852:860 arg1 CD24 862:865 Placental CD24 852:865 Placental CD24 852:865 Placental CD24 had an apparent molecular weight of 30-70 kDa consistent with its high degree of N- and O-linked glycosylation. 28012129 8 18 theme glycan 1050:1055 arg1 CD24 1069:1072 CD24 1069:1072 CD24 1069:1072 EDTA-sensitive CD24-Siglec-10 interaction via the terminal sialic acid glycan residues of CD24 was observed. 28012129 8 18 theme glycan 1050:1055 arg1 residues 1057:1064 the terminal sialic acid glycan residues 1025:1064 the terminal sialic acid glycan residues of CD24 1025:1072 EDTA-sensitive CD24-Siglec-10 interaction via the terminal sialic acid glycan residues of CD24 was observed. 28012129 0 19 theme fetal-maternal 103:116 arg1 interface 118:126 the fetal-maternal interface 99:126 the fetal-maternal interface 99:126 Expression of CD24 and Siglec-10 in first trimester placenta: implications for immune tolerance at the fetal-maternal interface. 28012129 14 20 theme fetal-maternal 1737:1750 arg1 interactions 1752:1763 fetal-maternal interactions 1737:1763 fetal-maternal interactions 1737:1763 The presence of the CD24-Siglec-10 in these regions of fetal-maternal interactions suggests a possible role in mediating immune tolerance at the fetal-maternal interface. 28012129 13 21 theme placenta 1606:1613 arg1 layers 1631:1636 the placenta cytotrophoblast layers 1602:1636 the placenta cytotrophoblast layers 1602:1636 This study is the first to demonstrate the early presence of CD24 in the placenta cytotrophoblast layers, placental bed and maternal uterine glands. 28012129 13 21 theme placenta 1606:1613 arg1 bed 1649:1651 placental bed 1639:1651 placental bed 1639:1651 This study is the first to demonstrate the early presence of CD24 in the placenta cytotrophoblast layers, placental bed and maternal uterine glands. 28012129 13 21 theme placenta 1606:1613 arg1 glands 1674:1679 maternal uterine glands 1657:1679 maternal uterine glands 1657:1679 This study is the first to demonstrate the early presence of CD24 in the placenta cytotrophoblast layers, placental bed and maternal uterine glands. 28012129 13 22 theme early 1576:1580 arg1 presence 1582:1589 the early presence 1572:1589 the early presence of CD24 in the placenta cytotrophoblast layers, placental bed and maternal uterine glands 1572:1679 This study is the first to demonstrate the early presence of CD24 in the placenta cytotrophoblast layers, placental bed and maternal uterine glands. 28012129 5 23 theme placental 674:682 arg1 CD24 684:687 placental CD24 674:687 placental CD24 674:687 Binding of recombinant Siglecs to placental CD24 was evaluated by ELISA. 28012129 14 24 from presence 1686:1693 arg1 regions 1726:1732 these regions 1720:1732 these regions of fetal-maternal interactions 1720:1763 The presence of the CD24-Siglec-10 in these regions of fetal-maternal interactions suggests a possible role in mediating immune tolerance at the fetal-maternal interface. 28012129 10 25 theme villous 1236:1242 arg1 cytotrophoblasts 1261:1276 villous and extravillous cytotrophoblasts 1236:1276 villous and extravillous cytotrophoblasts 1236:1276 During the first trimester, and already in gestational week (GA) 8, CD24 showed high expression in villous and extravillous cytotrophoblasts. 28012129 2 26 theme mucin-like 247:256 arg1 CD24 239:242 CD24 239:242 CD24 239:242 CD24, a mucin-like glycoprotein expressed at the surface of hematopoietic cells and diverse tumor cells, is known to interact with the sialic acid-binding immunoglobulin-type lectins (Siglecs). 28012129 2 26 theme mucin-like 247:256 arg1 glycoprotein 258:269 a mucin-like glycoprotein 245:269 a mucin-like glycoprotein expressed at the surface of hematopoietic cells and diverse tumor cells 245:341 CD24, a mucin-like glycoprotein expressed at the surface of hematopoietic cells and diverse tumor cells, is known to interact with the sialic acid-binding immunoglobulin-type lectins (Siglecs). 28012129 1 27 theme fetal-maternal 151:164 arg1 interface 166:174 the fetal-maternal interface 147:174 the fetal-maternal interface 147:174 During pregnancy, the fetal-maternal interface establishes immune tolerance between the fetus and the mother. 28012129 0 28 from Expression 0:9 arg1 placenta 52:59 first trimester placenta 36:59 first trimester placenta 36:59 Expression of CD24 and Siglec-10 in first trimester placenta: implications for immune tolerance at the fetal-maternal interface. 28012129 10 29 theme extravillous 1248:1259 arg1 cytotrophoblasts 1261:1276 villous and extravillous cytotrophoblasts 1236:1276 villous and extravillous cytotrophoblasts 1236:1276 During the first trimester, and already in gestational week (GA) 8, CD24 showed high expression in villous and extravillous cytotrophoblasts. 28012129 0 30 theme immune 79:84 arg1 tolerance 86:94 immune tolerance 79:94 immune tolerance 79:94 Expression of CD24 and Siglec-10 in first trimester placenta: implications for immune tolerance at the fetal-maternal interface. 28012129 7 31 theme glycosylation 964:976 arg1 degree 938:943 its high degree 929:943 its high degree of N- and O-linked glycosylation 929:976 Placental CD24 had an apparent molecular weight of 30-70 kDa consistent with its high degree of N- and O-linked glycosylation. 28012129 11 32 theme stromal 1315:1321 arg1 cells 1323:1327 stromal cells 1315:1327 stromal cells 1315:1327 There was also a mild expression in stromal cells, while syncytiotrophoblasts were negative. 28012129 2 33 theme acid-binding 381:392 arg1 lectins 414:420 the sialic acid-binding immunoglobulin-type lectins 370:420 the sialic acid-binding immunoglobulin-type lectins (Siglecs) 370:430 CD24, a mucin-like glycoprotein expressed at the surface of hematopoietic cells and diverse tumor cells, is known to interact with the sialic acid-binding immunoglobulin-type lectins (Siglecs). 28012129 2 33 theme acid-binding 381:392 arg1 Siglecs 423:429 Siglecs 423:429 Siglecs 423:429 CD24, a mucin-like glycoprotein expressed at the surface of hematopoietic cells and diverse tumor cells, is known to interact with the sialic acid-binding immunoglobulin-type lectins (Siglecs). 28012129 11 34 from expression 1301:1310 arg1 cells 1323:1327 stromal cells 1315:1327 stromal cells 1315:1327 There was also a mild expression in stromal cells, while syncytiotrophoblasts were negative. 28012129 4 35 theme was 544:546 arg1 affinity 548:555 CD24 was affinity 539:555 CD24 was affinity 539:555 CD24 was affinity purified from term placenta and characterized by SDS-PAGE, Western blot and ELISA. 28012129 0 36 theme CD24 14:17 arg1 Expression 0:9 Expression 0:9 Expression of CD24 and Siglec-10 in first trimester placenta: implications for immune tolerance at the fetal-maternal interface. 0:127 Expression of CD24 and Siglec-10 in first trimester placenta: implications for immune tolerance at the fetal-maternal interface. 28012129 0 37 theme Siglec-10 23:31 arg1 Expression 0:9 Expression 0:9 Expression of CD24 and Siglec-10 in first trimester placenta: implications for immune tolerance at the fetal-maternal interface. 0:127 Expression of CD24 and Siglec-10 in first trimester placenta: implications for immune tolerance at the fetal-maternal interface. 28012129 14 38 theme fetal-maternal 1827:1840 arg1 interface 1842:1850 the fetal-maternal interface 1823:1850 the fetal-maternal interface 1823:1850 The presence of the CD24-Siglec-10 in these regions of fetal-maternal interactions suggests a possible role in mediating immune tolerance at the fetal-maternal interface. 28012129 0 39 theme first 36:40 arg1 placenta 52:59 first trimester placenta 36:59 first trimester placenta 36:59 Expression of CD24 and Siglec-10 in first trimester placenta: implications for immune tolerance at the fetal-maternal interface. 28012129 13 40 theme maternal 1657:1664 arg1 layers 1631:1636 the placenta cytotrophoblast layers 1602:1636 the placenta cytotrophoblast layers 1602:1636 This study is the first to demonstrate the early presence of CD24 in the placenta cytotrophoblast layers, placental bed and maternal uterine glands. 28012129 13 40 theme maternal 1657:1664 arg1 glands 1674:1679 maternal uterine glands 1657:1679 maternal uterine glands 1657:1679 This study is the first to demonstrate the early presence of CD24 in the placenta cytotrophoblast layers, placental bed and maternal uterine glands. 28012129 2 41 theme tumor 331:335 arg1 cells 337:341 diverse tumor cells 323:341 diverse tumor cells 323:341 CD24, a mucin-like glycoprotein expressed at the surface of hematopoietic cells and diverse tumor cells, is known to interact with the sialic acid-binding immunoglobulin-type lectins (Siglecs). 28012129 14 42 theme immune 1803:1808 arg1 tolerance 1810:1818 immune tolerance 1803:1818 immune tolerance 1803:1818 The presence of the CD24-Siglec-10 in these regions of fetal-maternal interactions suggests a possible role in mediating immune tolerance at the fetal-maternal interface. 28012129 0 43 dep Expression 0:9 arg1 implications 62:73 implications 62:73 Expression of CD24 and Siglec-10 in first trimester placenta: implications for immune tolerance at the fetal-maternal interface. 0:127 Expression of CD24 and Siglec-10 in first trimester placenta: implications for immune tolerance at the fetal-maternal interface. 28012129 8 44 theme CD24-Siglec-10 994:1007 arg1 interaction 1009:1019 EDTA-sensitive CD24-Siglec-10 interaction 979:1019 EDTA-sensitive CD24-Siglec-10 interaction via the terminal sialic acid glycan residues of CD24 979:1072 EDTA-sensitive CD24-Siglec-10 interaction via the terminal sialic acid glycan residues of CD24 was observed. 28012129 3 45 theme immune 494:499 arg1 response 513:520 the immune suppression response 490:520 the immune suppression response in the placenta 490:536 This interaction was assessed as a candidate complex for the immune suppression response in the placenta. 28012129 7 46 theme consistent 913:922 arg1 weight 893:898 an apparent molecular weight 871:898 an apparent molecular weight of 30-70 kDa consistent with its high degree of N- and O-linked glycosylation 871:976 Placental CD24 had an apparent molecular weight of 30-70 kDa consistent with its high degree of N- and O-linked glycosylation. 28012129 10 47 theme high 1217:1220 arg1 expression 1222:1231 high expression 1217:1231 high expression in villous and extravillous cytotrophoblasts 1217:1276 During the first trimester, and already in gestational week (GA) 8, CD24 showed high expression in villous and extravillous cytotrophoblasts. 28012129 12 48 theme close 1487:1491 arg1 vicinity 1493:1500 close vicinity 1487:1500 close vicinity to extracellular trophoblasts 1487:1530 Co-localization of CD24 with Siglec-10 was observed in endometrial glands and in first trimester decidual cells in close vicinity to extracellular trophoblasts. 28012129 4 49 theme term 571:574 arg1 placenta 576:583 term placenta 571:583 term placenta 571:583 CD24 was affinity purified from term placenta and characterized by SDS-PAGE, Western blot and ELISA. 28012129 5 50 theme recombinant 651:661 arg1 Siglecs 663:669 recombinant Siglecs 651:669 recombinant Siglecs 651:669 Binding of recombinant Siglecs to placental CD24 was evaluated by ELISA. 28012129 13 51 theme cytotrophoblast 1615:1629 arg1 layers 1631:1636 the placenta cytotrophoblast layers 1602:1636 the placenta cytotrophoblast layers 1602:1636 This study is the first to demonstrate the early presence of CD24 in the placenta cytotrophoblast layers, placental bed and maternal uterine glands. 28012129 13 51 theme cytotrophoblast 1615:1629 arg1 bed 1649:1651 placental bed 1639:1651 placental bed 1639:1651 This study is the first to demonstrate the early presence of CD24 in the placenta cytotrophoblast layers, placental bed and maternal uterine glands. 28012129 13 51 theme cytotrophoblast 1615:1629 arg1 glands 1674:1679 maternal uterine glands 1657:1679 maternal uterine glands 1657:1679 This study is the first to demonstrate the early presence of CD24 in the placenta cytotrophoblast layers, placental bed and maternal uterine glands. 28012129 8 52 theme terminal 1029:1036 arg1 CD24 1069:1072 CD24 1069:1072 CD24 1069:1072 EDTA-sensitive CD24-Siglec-10 interaction via the terminal sialic acid glycan residues of CD24 was observed. 28012129 8 52 theme terminal 1029:1036 arg1 residues 1057:1064 the terminal sialic acid glycan residues 1025:1064 the terminal sialic acid glycan residues of CD24 1025:1072 EDTA-sensitive CD24-Siglec-10 interaction via the terminal sialic acid glycan residues of CD24 was observed. 28012129 10 53 from expression 1222:1231 arg1 cytotrophoblasts 1261:1276 villous and extravillous cytotrophoblasts 1236:1276 villous and extravillous cytotrophoblasts 1236:1276 During the first trimester, and already in gestational week (GA) 8, CD24 showed high expression in villous and extravillous cytotrophoblasts. 28012129 7 54 theme molecular 883:891 arg1 weight 893:898 an apparent molecular weight 871:898 an apparent molecular weight of 30-70 kDa consistent with its high degree of N- and O-linked glycosylation 871:976 Placental CD24 had an apparent molecular weight of 30-70 kDa consistent with its high degree of N- and O-linked glycosylation. 28012129 12 55 theme trimester 1459:1467 arg1 cells 1478:1482 first trimester decidual cells 1453:1482 first trimester decidual cells in close vicinity to extracellular trophoblasts 1453:1530 Co-localization of CD24 with Siglec-10 was observed in endometrial glands and in first trimester decidual cells in close vicinity to extracellular trophoblasts. 28012129 8 56 theme acid 1045:1048 arg1 CD24 1069:1072 CD24 1069:1072 CD24 1069:1072 EDTA-sensitive CD24-Siglec-10 interaction via the terminal sialic acid glycan residues of CD24 was observed. 28012129 8 56 theme acid 1045:1048 arg1 residues 1057:1064 the terminal sialic acid glycan residues 1025:1064 the terminal sialic acid glycan residues of CD24 1025:1072 EDTA-sensitive CD24-Siglec-10 interaction via the terminal sialic acid glycan residues of CD24 was observed. 28012129 12 57 theme endometrial 1427:1437 arg1 glands 1439:1444 endometrial glands 1427:1444 endometrial glands 1427:1444 Co-localization of CD24 with Siglec-10 was observed in endometrial glands and in first trimester decidual cells in close vicinity to extracellular trophoblasts. 28012129 13 58 theme CD24 1594:1597 arg1 presence 1582:1589 the early presence 1572:1589 the early presence of CD24 in the placenta cytotrophoblast layers, placental bed and maternal uterine glands 1572:1679 This study is the first to demonstrate the early presence of CD24 in the placenta cytotrophoblast layers, placental bed and maternal uterine glands. 28012129 1 59 theme immune 188:193 arg1 tolerance 195:203 immune tolerance 188:203 immune tolerance between the fetus and the mother 188:236 During pregnancy, the fetal-maternal interface establishes immune tolerance between the fetus and the mother. 28012129 12 60 theme CD24 1391:1394 arg1 Co-localization 1372:1386 Co-localization 1372:1386 Co-localization of CD24 with Siglec-10 1372:1409 Co-localization of CD24 with Siglec-10 was observed in endometrial glands and in first trimester decidual cells in close vicinity to extracellular trophoblasts. 28012129 13 61 from presence 1582:1589 arg1 layers 1631:1636 the placenta cytotrophoblast layers 1602:1636 the placenta cytotrophoblast layers 1602:1636 This study is the first to demonstrate the early presence of CD24 in the placenta cytotrophoblast layers, placental bed and maternal uterine glands. 28012129 13 61 from presence 1582:1589 arg1 bed 1649:1651 placental bed 1639:1651 placental bed 1639:1651 This study is the first to demonstrate the early presence of CD24 in the placenta cytotrophoblast layers, placental bed and maternal uterine glands. 28012129 13 61 from presence 1582:1589 arg1 glands 1674:1679 maternal uterine glands 1657:1679 maternal uterine glands 1657:1679 This study is the first to demonstrate the early presence of CD24 in the placenta cytotrophoblast layers, placental bed and maternal uterine glands. 28012129 6 62 theme trimester 759:767 arg1 tissues 779:785 first trimester placental tissues 753:785 first trimester placental tissues 753:785 The expression of CD24 and Siglec-10 in first trimester placental tissues was investigated by immunohistochemistry and immunofluorescence. 28012129 2 63 theme hematopoietic 299:311 arg1 cells 313:317 hematopoietic cells 299:317 hematopoietic cells 299:317 CD24, a mucin-like glycoprotein expressed at the surface of hematopoietic cells and diverse tumor cells, is known to interact with the sialic acid-binding immunoglobulin-type lectins (Siglecs). 28012129 14 64 theme CD24-Siglec-10 1702:1715 arg1 presence 1686:1693 The presence 1682:1693 The presence of the CD24-Siglec-10 in these regions of fetal-maternal interactions 1682:1763 The presence of the CD24-Siglec-10 in these regions of fetal-maternal interactions suggests a possible role in mediating immune tolerance at the fetal-maternal interface. 28012129 3 65 theme candidate 468:476 arg1 interaction 438:448 This interaction 433:448 This interaction 433:448 This interaction was assessed as a candidate complex for the immune suppression response in the placenta. 28012129 3 65 theme candidate 468:476 arg1 complex 478:484 a candidate complex 466:484 a candidate complex for the immune suppression response in the placenta 466:536 This interaction was assessed as a candidate complex for the immune suppression response in the placenta. 28012129 12 66 located observed 1415:1422 arg2 Co-localization 1372:1386 Co-localization 1372:1386 Co-localization of CD24 with Siglec-10 1372:1409 Co-localization of CD24 with Siglec-10 was observed in endometrial glands and in first trimester decidual cells in close vicinity to extracellular trophoblasts. 28012129 12 66 located observed 1415:1422 arg1 glands 1439:1444 endometrial glands 1427:1444 endometrial glands 1427:1444 Co-localization of CD24 with Siglec-10 was observed in endometrial glands and in first trimester decidual cells in close vicinity to extracellular trophoblasts. 28012129 7 67 link O-linked 955:962 arg1 glycosylation 964:976 O-linked glycosylation 955:976 O-linked glycosylation 955:976 Placental CD24 had an apparent molecular weight of 30-70 kDa consistent with its high degree of N- and O-linked glycosylation. 28012129 8 68 theme CD24 1069:1072 arg1 CD24 1069:1072 CD24 1069:1072 CD24 1069:1072 EDTA-sensitive CD24-Siglec-10 interaction via the terminal sialic acid glycan residues of CD24 was observed. 28012129 8 68 theme CD24 1069:1072 arg1 residues 1057:1064 the terminal sialic acid glycan residues 1025:1064 the terminal sialic acid glycan residues of CD24 1025:1072 EDTA-sensitive CD24-Siglec-10 interaction via the terminal sialic acid glycan residues of CD24 was observed. 28012129 11 69 theme mild 1296:1299 arg1 expression 1301:1310 a mild expression 1294:1310 a mild expression in stromal cells 1294:1327 There was also a mild expression in stromal cells, while syncytiotrophoblasts were negative. 28012129 2 70 theme sialic 374:379 arg1 lectins 414:420 the sialic acid-binding immunoglobulin-type lectins 370:420 the sialic acid-binding immunoglobulin-type lectins (Siglecs) 370:430 CD24, a mucin-like glycoprotein expressed at the surface of hematopoietic cells and diverse tumor cells, is known to interact with the sialic acid-binding immunoglobulin-type lectins (Siglecs). 28012129 2 70 theme sialic 374:379 arg1 Siglecs 423:429 Siglecs 423:429 Siglecs 423:429 CD24, a mucin-like glycoprotein expressed at the surface of hematopoietic cells and diverse tumor cells, is known to interact with the sialic acid-binding immunoglobulin-type lectins (Siglecs). 28012129 7 71 theme O-linked 955:962 arg1 glycosylation 964:976 O-linked glycosylation 955:976 O-linked glycosylation 955:976 Placental CD24 had an apparent molecular weight of 30-70 kDa consistent with its high degree of N- and O-linked glycosylation. 28012129 14 72 attach presence 1686:1693 arg1 regions 1726:1732 these regions 1720:1732 these regions of fetal-maternal interactions 1720:1763 The presence of the CD24-Siglec-10 in these regions of fetal-maternal interactions suggests a possible role in mediating immune tolerance at the fetal-maternal interface. 28012129 14 72 attach presence 1686:1693 arg2 CD24-Siglec-10 1702:1715 the CD24-Siglec-10 1698:1715 the CD24-Siglec-10 1698:1715 The presence of the CD24-Siglec-10 in these regions of fetal-maternal interactions suggests a possible role in mediating immune tolerance at the fetal-maternal interface. 28012129 7 73 theme N- 948:949 arg1 degree 938:943 its high degree 929:943 its high degree of N- and O-linked glycosylation 929:976 Placental CD24 had an apparent molecular weight of 30-70 kDa consistent with its high degree of N- and O-linked glycosylation. 28012129 13 74 attach presence 1582:1589 arg2 CD24 1594:1597 CD24 1594:1597 CD24 1594:1597 This study is the first to demonstrate the early presence of CD24 in the placenta cytotrophoblast layers, placental bed and maternal uterine glands. 28012129 13 74 attach presence 1582:1589 arg1 bed 1649:1651 placental bed 1639:1651 placental bed 1639:1651 This study is the first to demonstrate the early presence of CD24 in the placenta cytotrophoblast layers, placental bed and maternal uterine glands. 28012129 13 74 attach presence 1582:1589 arg1 glands 1674:1679 maternal uterine glands 1657:1679 maternal uterine glands 1657:1679 This study is the first to demonstrate the early presence of CD24 in the placenta cytotrophoblast layers, placental bed and maternal uterine glands. 28012129 13 74 attach presence 1582:1589 arg1 layers 1631:1636 the placenta cytotrophoblast layers 1602:1636 the placenta cytotrophoblast layers 1602:1636 This study is the first to demonstrate the early presence of CD24 in the placenta cytotrophoblast layers, placental bed and maternal uterine glands. 28012129 10 75 theme first 1148:1152 arg1 trimester 1154:1162 the first trimester 1144:1162 the first trimester 1144:1162 During the first trimester, and already in gestational week (GA) 8, CD24 showed high expression in villous and extravillous cytotrophoblasts. 28012129 0 76 from interface 118:126 arg1 implications 62:73 implications 62:73 Expression of CD24 and Siglec-10 in first trimester placenta: implications for immune tolerance at the fetal-maternal interface. 0:127 Expression of CD24 and Siglec-10 in first trimester placenta: implications for immune tolerance at the fetal-maternal interface. 28012129 6 77 theme first 753:757 arg1 tissues 779:785 first trimester placental tissues 753:785 first trimester placental tissues 753:785 The expression of CD24 and Siglec-10 in first trimester placental tissues was investigated by immunohistochemistry and immunofluorescence. 28012129 2 78 theme immunoglobulin-type 394:412 arg1 lectins 414:420 the sialic acid-binding immunoglobulin-type lectins 370:420 the sialic acid-binding immunoglobulin-type lectins (Siglecs) 370:430 CD24, a mucin-like glycoprotein expressed at the surface of hematopoietic cells and diverse tumor cells, is known to interact with the sialic acid-binding immunoglobulin-type lectins (Siglecs). 28012129 2 78 theme immunoglobulin-type 394:412 arg1 Siglecs 423:429 Siglecs 423:429 Siglecs 423:429 CD24, a mucin-like glycoprotein expressed at the surface of hematopoietic cells and diverse tumor cells, is known to interact with the sialic acid-binding immunoglobulin-type lectins (Siglecs). 28012129 0 79 theme trimester 42:50 arg1 placenta 52:59 first trimester placenta 36:59 first trimester placenta 36:59 Expression of CD24 and Siglec-10 in first trimester placenta: implications for immune tolerance at the fetal-maternal interface. 28012129 10 80 theme gestational 1180:1190 arg1 GA 1198:1199 GA 1198:1199 GA 1198:1199 During the first trimester, and already in gestational week (GA) 8, CD24 showed high expression in villous and extravillous cytotrophoblasts. 28012129 10 80 theme gestational 1180:1190 arg1 week 1192:1195 gestational week (GA) 8 1180:1202 gestational week (GA) 8 1180:1202 During the first trimester, and already in gestational week (GA) 8, CD24 showed high expression in villous and extravillous cytotrophoblasts. 28012129 4 81 theme CD24 539:542 arg1 affinity 548:555 CD24 was affinity 539:555 CD24 was affinity 539:555 CD24 was affinity purified from term placenta and characterized by SDS-PAGE, Western blot and ELISA. 28012129 7 82 contain had 867:869 arg2 weight 893:898 an apparent molecular weight 871:898 an apparent molecular weight of 30-70 kDa consistent with its high degree of N- and O-linked glycosylation 871:976 Placental CD24 had an apparent molecular weight of 30-70 kDa consistent with its high degree of N- and O-linked glycosylation. 28012129 7 82 contain had 867:869 arg1 CD24 862:865 Placental CD24 852:865 Placental CD24 852:865 Placental CD24 had an apparent molecular weight of 30-70 kDa consistent with its high degree of N- and O-linked glycosylation. 28012129 6 83 theme Siglec-10 740:748 arg1 expression 717:726 The expression 713:726 The expression of CD24 and Siglec-10 in first trimester placental tissues 713:785 The expression of CD24 and Siglec-10 in first trimester placental tissues was investigated by immunohistochemistry and immunofluorescence. 28012129 2 84 theme cells 337:341 arg1 surface 288:294 the surface 284:294 the surface of hematopoietic cells and diverse tumor cells 284:341 CD24, a mucin-like glycoprotein expressed at the surface of hematopoietic cells and diverse tumor cells, is known to interact with the sialic acid-binding immunoglobulin-type lectins (Siglecs). 28012129 7 85 theme high 933:936 arg1 degree 938:943 its high degree 929:943 its high degree of N- and O-linked glycosylation 929:976 Placental CD24 had an apparent molecular weight of 30-70 kDa consistent with its high degree of N- and O-linked glycosylation. 28012129 13 86 theme uterine 1666:1672 arg1 layers 1631:1636 the placenta cytotrophoblast layers 1602:1636 the placenta cytotrophoblast layers 1602:1636 This study is the first to demonstrate the early presence of CD24 in the placenta cytotrophoblast layers, placental bed and maternal uterine glands. 28012129 13 86 theme uterine 1666:1672 arg1 glands 1674:1679 maternal uterine glands 1657:1679 maternal uterine glands 1657:1679 This study is the first to demonstrate the early presence of CD24 in the placenta cytotrophoblast layers, placental bed and maternal uterine glands. 28012129 6 87 theme CD24 731:734 arg1 expression 717:726 The expression 713:726 The expression of CD24 and Siglec-10 in first trimester placental tissues 713:785 The expression of CD24 and Siglec-10 in first trimester placental tissues was investigated by immunohistochemistry and immunofluorescence. 28012129 2 88 theme diverse 323:329 arg1 cells 337:341 diverse tumor cells 323:341 diverse tumor cells 323:341 CD24, a mucin-like glycoprotein expressed at the surface of hematopoietic cells and diverse tumor cells, is known to interact with the sialic acid-binding immunoglobulin-type lectins (Siglecs). 28012129 12 89 theme extracellular 1505:1517 arg1 trophoblasts 1519:1530 extracellular trophoblasts 1505:1530 extracellular trophoblasts 1505:1530 Co-localization of CD24 with Siglec-10 was observed in endometrial glands and in first trimester decidual cells in close vicinity to extracellular trophoblasts. 28012129 6 90 from expression 717:726 arg1 tissues 779:785 first trimester placental tissues 753:785 first trimester placental tissues 753:785 The expression of CD24 and Siglec-10 in first trimester placental tissues was investigated by immunohistochemistry and immunofluorescence. 28012129 4 91 theme Western 616:622 arg1 blot 624:627 Western blot 616:627 Western blot 616:627 CD24 was affinity purified from term placenta and characterized by SDS-PAGE, Western blot and ELISA. 28012129 7 92 theme 30-70 kDa 903:911 arg1 weight 893:898 an apparent molecular weight 871:898 an apparent molecular weight of 30-70 kDa consistent with its high degree of N- and O-linked glycosylation 871:976 Placental CD24 had an apparent molecular weight of 30-70 kDa consistent with its high degree of N- and O-linked glycosylation. 24713701 3 0 theme -based 477:482 arg1 screen 495:500 a SILAC (stable isotope labeling of amino acids in cell culture)-based proteomics screen 413:500 a SILAC (stable isotope labeling of amino acids in cell culture)-based proteomics screen 413:500 Using a SILAC (stable isotope labeling of amino acids in cell culture)-based proteomics screen, we quantified the changes in mitochondrial protein expression in OGT- and OGA-overexpressing cells. 24713701 3 1 theme proteomics 484:493 arg1 screen 495:500 a SILAC (stable isotope labeling of amino acids in cell culture)-based proteomics screen 413:500 a SILAC (stable isotope labeling of amino acids in cell culture)-based proteomics screen 413:500 Using a SILAC (stable isotope labeling of amino acids in cell culture)-based proteomics screen, we quantified the changes in mitochondrial protein expression in OGT- and OGA-overexpressing cells. 24713701 7 2 theme metabolite 1018:1027 arg1 production 1029:1038 metabolite production 1018:1038 metabolite production 1018:1038 These data demonstrate that alterations in O-GlcNAc cycling profoundly affect energy and metabolite production. 24713701 1 3 theme Mitochondrial 81:93 arg1 impairment 95:104 Mitochondrial impairment 81:104 Mitochondrial impairment 81:104 Mitochondrial impairment is commonly found in many diseases such as diabetes, cancer, and Alzheimer disease. 24713701 3 4 theme mitochondrial 532:544 arg1 expression 554:563 mitochondrial protein expression 532:563 mitochondrial protein expression in OGT- and OGA-overexpressing cells 532:600 Using a SILAC (stable isotope labeling of amino acids in cell culture)-based proteomics screen, we quantified the changes in mitochondrial protein expression in OGT- and OGA-overexpressing cells. 24713701 3 5 dep -based 477:482 arg1 labeling 437:444 stable isotope labeling 422:444 stable isotope labeling of amino acids in cell culture 422:475 Using a SILAC (stable isotope labeling of amino acids in cell culture)-based proteomics screen, we quantified the changes in mitochondrial protein expression in OGT- and OGA-overexpressing cells. 24713701 0 6 link O-linked 9:16 arg1 cycling 40:46 O-linked β-N-acetylglucosamine cycling 9:46 O-linked β-N-acetylglucosamine cycling 9:46 Altering O-linked β-N-acetylglucosamine cycling disrupts mitochondrial function. 24713701 2 7 theme O-GlcNAc 292:299 arg1 OGA 336:338 OGA 336:338 OGA 336:338 We demonstrate that the enzymes responsible for the addition or removal of the O-GlcNAc modification, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), respectively, are critical regulators of mitochondrial function. 24713701 2 7 theme O-GlcNAc 292:299 arg1 OGT 314:316 OGT 314:316 OGT 314:316 We demonstrate that the enzymes responsible for the addition or removal of the O-GlcNAc modification, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), respectively, are critical regulators of mitochondrial function. 24713701 2 7 theme O-GlcNAc 292:299 arg1 transferase 301:311 O-GlcNAc transferase 292:311 O-GlcNAc transferase (OGT) 292:317 We demonstrate that the enzymes responsible for the addition or removal of the O-GlcNAc modification, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), respectively, are critical regulators of mitochondrial function. 24713701 2 7 theme O-GlcNAc 292:299 arg1 enzymes 214:220 the enzymes 210:220 the enzymes responsible for the addition or removal of the O-GlcNAc modification 210:289 We demonstrate that the enzymes responsible for the addition or removal of the O-GlcNAc modification, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), respectively, are critical regulators of mitochondrial function. 24713701 4 8 from decreases 663:671 arg1 proteins 699:706 mitochondria-localized proteins 676:706 mitochondria-localized proteins involved in the respiratory chain and the tricarboxylic acid cycle 676:773 Strikingly, overexpression of OGT or OGA showed significant decreases in mitochondria-localized proteins involved in the respiratory chain and the tricarboxylic acid cycle. 24713701 4 9 theme respiratory 724:734 arg1 chain 736:740 the respiratory chain 720:740 the respiratory chain 720:740 Strikingly, overexpression of OGT or OGA showed significant decreases in mitochondria-localized proteins involved in the respiratory chain and the tricarboxylic acid cycle. 24713701 7 10 from alterations 957:967 arg1 cycling 981:987 O-GlcNAc cycling 972:987 O-GlcNAc cycling 972:987 These data demonstrate that alterations in O-GlcNAc cycling profoundly affect energy and metabolite production. 24713701 2 11 theme mitochondrial 383:395 arg1 function 397:404 mitochondrial function 383:404 mitochondrial function 383:404 We demonstrate that the enzymes responsible for the addition or removal of the O-GlcNAc modification, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), respectively, are critical regulators of mitochondrial function. 24713701 5 12 theme mitochondrial 789:801 arg1 morphology 803:812 mitochondrial morphology 789:812 mitochondrial morphology 789:812 Furthermore, mitochondrial morphology was altered in these cells. 24713701 2 13 theme modification 278:289 arg1 addition 242:249 addition 242:249 addition 242:249 We demonstrate that the enzymes responsible for the addition or removal of the O-GlcNAc modification, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), respectively, are critical regulators of mitochondrial function. 24713701 2 13 theme modification 278:289 arg1 removal 254:260 removal 254:260 removal 254:260 We demonstrate that the enzymes responsible for the addition or removal of the O-GlcNAc modification, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), respectively, are critical regulators of mitochondrial function. 24713701 3 14 theme isotope 429:435 arg1 labeling 437:444 stable isotope labeling 422:444 stable isotope labeling of amino acids in cell culture 422:475 Using a SILAC (stable isotope labeling of amino acids in cell culture)-based proteomics screen, we quantified the changes in mitochondrial protein expression in OGT- and OGA-overexpressing cells. 24713701 0 15 theme O-linked 9:16 arg1 cycling 40:46 O-linked β-N-acetylglucosamine cycling 9:46 O-linked β-N-acetylglucosamine cycling 9:46 Altering O-linked β-N-acetylglucosamine cycling disrupts mitochondrial function. 24713701 6 16 theme OGT/OGA-overexpressing 899:920 arg1 cells 922:926 OGT/OGA-overexpressing cells 899:926 OGT/OGA-overexpressing cells 899:926 Both cellular respiration and glycolysis were reduced in OGT/OGA-overexpressing cells. 24713701 4 17 theme OGA 640:642 arg1 overexpression 615:628 overexpression 615:628 overexpression of OGT or OGA 615:642 Strikingly, overexpression of OGT or OGA showed significant decreases in mitochondria-localized proteins involved in the respiratory chain and the tricarboxylic acid cycle. 24713701 3 18 theme protein 546:552 arg1 expression 554:563 mitochondrial protein expression 532:563 mitochondrial protein expression in OGT- and OGA-overexpressing cells 532:600 Using a SILAC (stable isotope labeling of amino acids in cell culture)-based proteomics screen, we quantified the changes in mitochondrial protein expression in OGT- and OGA-overexpressing cells. 24713701 2 19 theme critical 360:367 arg1 enzymes 214:220 the enzymes 210:220 the enzymes responsible for the addition or removal of the O-GlcNAc modification 210:289 We demonstrate that the enzymes responsible for the addition or removal of the O-GlcNAc modification, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), respectively, are critical regulators of mitochondrial function. 24713701 2 19 theme critical 360:367 arg1 regulators 369:378 critical regulators 360:378 critical regulators of mitochondrial function 360:404 We demonstrate that the enzymes responsible for the addition or removal of the O-GlcNAc modification, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), respectively, are critical regulators of mitochondrial function. 24713701 7 20 theme O-GlcNAc 972:979 arg1 cycling 981:987 O-GlcNAc cycling 972:987 O-GlcNAc cycling 972:987 These data demonstrate that alterations in O-GlcNAc cycling profoundly affect energy and metabolite production. 24713701 1 21 theme many 127:130 arg1 diabetes 149:156 diabetes 149:156 diabetes 149:156 Mitochondrial impairment is commonly found in many diseases such as diabetes, cancer, and Alzheimer disease. 24713701 1 21 theme many 127:130 arg1 disease 181:187 Alzheimer disease 171:187 Alzheimer disease 171:187 Mitochondrial impairment is commonly found in many diseases such as diabetes, cancer, and Alzheimer disease. 24713701 1 21 theme many 127:130 arg1 cancer 159:164 cancer 159:164 cancer 159:164 Mitochondrial impairment is commonly found in many diseases such as diabetes, cancer, and Alzheimer disease. 24713701 1 21 theme many 127:130 arg1 diseases 132:139 many diseases 127:139 many diseases such as diabetes, cancer, and Alzheimer disease 127:187 Mitochondrial impairment is commonly found in many diseases such as diabetes, cancer, and Alzheimer disease. 24713701 3 22 theme amino 449:453 arg1 acids 455:459 amino acids 449:459 amino acids 449:459 Using a SILAC (stable isotope labeling of amino acids in cell culture)-based proteomics screen, we quantified the changes in mitochondrial protein expression in OGT- and OGA-overexpressing cells. 24713701 0 23 theme β-N-acetylglucosamine 18:38 arg1 cycling 40:46 O-linked β-N-acetylglucosamine cycling 9:46 O-linked β-N-acetylglucosamine cycling 9:46 Altering O-linked β-N-acetylglucosamine cycling disrupts mitochondrial function. 24713701 1 24 theme Alzheimer 171:179 arg1 disease 181:187 Alzheimer disease 171:187 Alzheimer disease 171:187 Mitochondrial impairment is commonly found in many diseases such as diabetes, cancer, and Alzheimer disease. 24713701 3 25 theme acids 455:459 arg1 labeling 437:444 stable isotope labeling 422:444 stable isotope labeling of amino acids in cell culture 422:475 Using a SILAC (stable isotope labeling of amino acids in cell culture)-based proteomics screen, we quantified the changes in mitochondrial protein expression in OGT- and OGA-overexpressing cells. 24713701 0 26 theme mitochondrial 57:69 arg1 function 71:78 mitochondrial function 57:78 mitochondrial function 57:78 Altering O-linked β-N-acetylglucosamine cycling disrupts mitochondrial function. 24713701 4 27 theme OGT 633:635 arg1 overexpression 615:628 overexpression 615:628 overexpression of OGT or OGA 615:642 Strikingly, overexpression of OGT or OGA showed significant decreases in mitochondria-localized proteins involved in the respiratory chain and the tricarboxylic acid cycle. 24713701 4 28 theme significant 651:661 arg1 decreases 663:671 significant decreases 651:671 significant decreases in mitochondria-localized proteins involved in the respiratory chain and the tricarboxylic acid cycle 651:773 Strikingly, overexpression of OGT or OGA showed significant decreases in mitochondria-localized proteins involved in the respiratory chain and the tricarboxylic acid cycle. 24713701 3 29 theme stable 422:427 arg1 labeling 437:444 stable isotope labeling 422:444 stable isotope labeling of amino acids in cell culture 422:475 Using a SILAC (stable isotope labeling of amino acids in cell culture)-based proteomics screen, we quantified the changes in mitochondrial protein expression in OGT- and OGA-overexpressing cells. 24713701 3 30 theme OGA-overexpressing 577:594 arg1 cells 596:600 OGT- and OGA-overexpressing cells 568:600 OGT- and OGA-overexpressing cells 568:600 Using a SILAC (stable isotope labeling of amino acids in cell culture)-based proteomics screen, we quantified the changes in mitochondrial protein expression in OGT- and OGA-overexpressing cells. 24713701 3 31 from labeling 437:444 arg1 culture 469:475 cell culture 464:475 cell culture 464:475 Using a SILAC (stable isotope labeling of amino acids in cell culture)-based proteomics screen, we quantified the changes in mitochondrial protein expression in OGT- and OGA-overexpressing cells. 24713701 2 32 theme function 397:404 arg1 enzymes 214:220 the enzymes 210:220 the enzymes responsible for the addition or removal of the O-GlcNAc modification 210:289 We demonstrate that the enzymes responsible for the addition or removal of the O-GlcNAc modification, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), respectively, are critical regulators of mitochondrial function. 24713701 2 32 theme function 397:404 arg1 regulators 369:378 critical regulators 360:378 critical regulators of mitochondrial function 360:404 We demonstrate that the enzymes responsible for the addition or removal of the O-GlcNAc modification, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), respectively, are critical regulators of mitochondrial function. 24713701 3 33 from changes 521:527 arg1 expression 554:563 mitochondrial protein expression 532:563 mitochondrial protein expression in OGT- and OGA-overexpressing cells 532:600 Using a SILAC (stable isotope labeling of amino acids in cell culture)-based proteomics screen, we quantified the changes in mitochondrial protein expression in OGT- and OGA-overexpressing cells. 24713701 1 34 located found 118:122 arg1 diabetes 149:156 diabetes 149:156 diabetes 149:156 Mitochondrial impairment is commonly found in many diseases such as diabetes, cancer, and Alzheimer disease. 24713701 1 34 located found 118:122 arg1 disease 181:187 Alzheimer disease 171:187 Alzheimer disease 171:187 Mitochondrial impairment is commonly found in many diseases such as diabetes, cancer, and Alzheimer disease. 24713701 1 34 located found 118:122 arg1 cancer 159:164 cancer 159:164 cancer 159:164 Mitochondrial impairment is commonly found in many diseases such as diabetes, cancer, and Alzheimer disease. 24713701 1 34 located found 118:122 arg2 impairment 95:104 Mitochondrial impairment 81:104 Mitochondrial impairment 81:104 Mitochondrial impairment is commonly found in many diseases such as diabetes, cancer, and Alzheimer disease. 24713701 1 34 located found 118:122 arg1 diseases 132:139 many diseases 127:139 many diseases such as diabetes, cancer, and Alzheimer disease 127:187 Mitochondrial impairment is commonly found in many diseases such as diabetes, cancer, and Alzheimer disease. 24713701 2 35 theme responsible 222:232 arg1 O-GlcNAcase 323:333 O-GlcNAcase 323:333 O-GlcNAcase 323:333 We demonstrate that the enzymes responsible for the addition or removal of the O-GlcNAc modification, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), respectively, are critical regulators of mitochondrial function. 24713701 2 35 theme responsible 222:232 arg1 transferase 301:311 O-GlcNAc transferase 292:311 O-GlcNAc transferase (OGT) 292:317 We demonstrate that the enzymes responsible for the addition or removal of the O-GlcNAc modification, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), respectively, are critical regulators of mitochondrial function. 24713701 2 35 theme responsible 222:232 arg1 enzymes 214:220 the enzymes 210:220 the enzymes responsible for the addition or removal of the O-GlcNAc modification 210:289 We demonstrate that the enzymes responsible for the addition or removal of the O-GlcNAc modification, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), respectively, are critical regulators of mitochondrial function. 24713701 2 35 theme responsible 222:232 arg1 regulators 369:378 critical regulators 360:378 critical regulators of mitochondrial function 360:404 We demonstrate that the enzymes responsible for the addition or removal of the O-GlcNAc modification, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), respectively, are critical regulators of mitochondrial function. 24713701 3 36 theme OGT- 568:571 arg1 cells 596:600 OGT- and OGA-overexpressing cells 568:600 OGT- and OGA-overexpressing cells 568:600 Using a SILAC (stable isotope labeling of amino acids in cell culture)-based proteomics screen, we quantified the changes in mitochondrial protein expression in OGT- and OGA-overexpressing cells. 24713701 2 37 theme O-GlcNAc 269:276 arg1 modification 278:289 the O-GlcNAc modification 265:289 the O-GlcNAc modification 265:289 We demonstrate that the enzymes responsible for the addition or removal of the O-GlcNAc modification, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), respectively, are critical regulators of mitochondrial function. 24713701 4 38 theme acid 764:767 arg1 cycle 769:773 the tricarboxylic acid cycle 746:773 the tricarboxylic acid cycle 746:773 Strikingly, overexpression of OGT or OGA showed significant decreases in mitochondria-localized proteins involved in the respiratory chain and the tricarboxylic acid cycle. 24713701 6 39 theme cellular 847:854 arg1 respiration 856:866 cellular respiration 847:866 cellular respiration 847:866 Both cellular respiration and glycolysis were reduced in OGT/OGA-overexpressing cells. 24713701 4 40 theme tricarboxylic 750:762 arg1 cycle 769:773 the tricarboxylic acid cycle 746:773 the tricarboxylic acid cycle 746:773 Strikingly, overexpression of OGT or OGA showed significant decreases in mitochondria-localized proteins involved in the respiratory chain and the tricarboxylic acid cycle. 24713701 3 41 theme cell 464:467 arg1 culture 469:475 cell culture 464:475 cell culture 464:475 Using a SILAC (stable isotope labeling of amino acids in cell culture)-based proteomics screen, we quantified the changes in mitochondrial protein expression in OGT- and OGA-overexpressing cells. 24713701 2 42 dep addition 242:249 arg1 the 238:240 the 238:240 the 238:240 We demonstrate that the enzymes responsible for the addition or removal of the O-GlcNAc modification, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), respectively, are critical regulators of mitochondrial function. 24713701 4 43 theme mitochondria-localized 676:697 arg1 proteins 699:706 mitochondria-localized proteins 676:706 mitochondria-localized proteins involved in the respiratory chain and the tricarboxylic acid cycle 676:773 Strikingly, overexpression of OGT or OGA showed significant decreases in mitochondria-localized proteins involved in the respiratory chain and the tricarboxylic acid cycle. 24713701 3 44 from expression 554:563 arg1 cells 596:600 OGT- and OGA-overexpressing cells 568:600 OGT- and OGA-overexpressing cells 568:600 Using a SILAC (stable isotope labeling of amino acids in cell culture)-based proteomics screen, we quantified the changes in mitochondrial protein expression in OGT- and OGA-overexpressing cells. 24616106 3 0 with association 520:530 arg1 transferase 554:564 O-GlcNAc transferase 545:564 O-GlcNAc transferase 545:564 We report that association of TLEs with O-GlcNAc transferase, an enzyme that catalyzes posttranslational modification of proteins by O-linked N-acetylglucosamine, is essential for TLE-mediated transcriptional repression. 24616106 3 0 with association 520:530 arg1 enzyme 570:575 an enzyme 567:575 an enzyme that catalyzes posttranslational modification of proteins by O-linked N-acetylglucosamine 567:665 We report that association of TLEs with O-GlcNAc transferase, an enzyme that catalyzes posttranslational modification of proteins by O-linked N-acetylglucosamine, is essential for TLE-mediated transcriptional repression. 24616106 4 1 theme gene 766:769 arg1 promoters 771:779 Wnt-responsive gene promoters 751:779 Wnt-responsive gene promoters 751:779 Removal of O-GlcNAc from Wnt-responsive gene promoters is critical for gene activation from Wnt-responsive promoters. 24616106 1 2 theme critical 236:243 arg1 orthologues 174:184 its mammalian orthologues 160:184 its mammalian orthologues 160:184 The Drosophila Groucho protein and its mammalian orthologues the transducin-like enhancers of split (TLEs) are critical transcriptional corepressors that repress Wnt and other signaling pathways. 24616106 1 2 theme critical 236:243 arg1 protein 148:154 The Drosophila Groucho protein 125:154 The Drosophila Groucho protein 125:154 The Drosophila Groucho protein and its mammalian orthologues the transducin-like enhancers of split (TLEs) are critical transcriptional corepressors that repress Wnt and other signaling pathways. 24616106 1 2 theme critical 236:243 arg1 corepressors 261:272 critical transcriptional corepressors 236:272 critical transcriptional corepressors that repress Wnt and other signaling pathways 236:318 The Drosophila Groucho protein and its mammalian orthologues the transducin-like enhancers of split (TLEs) are critical transcriptional corepressors that repress Wnt and other signaling pathways. 24616106 3 3 link O-linked 638:645 arg1 N-acetylglucosamine 647:665 O-linked N-acetylglucosamine 638:665 O-linked N-acetylglucosamine 638:665 We report that association of TLEs with O-GlcNAc transferase, an enzyme that catalyzes posttranslational modification of proteins by O-linked N-acetylglucosamine, is essential for TLE-mediated transcriptional repression. 24616106 4 4 theme Wnt-responsive 751:764 arg1 promoters 771:779 Wnt-responsive gene promoters 751:779 Wnt-responsive gene promoters 751:779 Removal of O-GlcNAc from Wnt-responsive gene promoters is critical for gene activation from Wnt-responsive promoters. 24616106 1 5 theme transcriptional 245:259 arg1 orthologues 174:184 its mammalian orthologues 160:184 its mammalian orthologues 160:184 The Drosophila Groucho protein and its mammalian orthologues the transducin-like enhancers of split (TLEs) are critical transcriptional corepressors that repress Wnt and other signaling pathways. 24616106 1 5 theme transcriptional 245:259 arg1 protein 148:154 The Drosophila Groucho protein 125:154 The Drosophila Groucho protein 125:154 The Drosophila Groucho protein and its mammalian orthologues the transducin-like enhancers of split (TLEs) are critical transcriptional corepressors that repress Wnt and other signaling pathways. 24616106 1 5 theme transcriptional 245:259 arg1 corepressors 261:272 critical transcriptional corepressors 236:272 critical transcriptional corepressors that repress Wnt and other signaling pathways 236:318 The Drosophila Groucho protein and its mammalian orthologues the transducin-like enhancers of split (TLEs) are critical transcriptional corepressors that repress Wnt and other signaling pathways. 24616106 0 6 theme repression 86:95 arg1 enhancer 53:60 transducin-like enhancer 37:60 transducin-like enhancer of split (TLE)-mediated repression of canonical Wnt signaling 37:122 O-GlcNAc transferase is critical for transducin-like enhancer of split (TLE)-mediated repression of canonical Wnt signaling. 24616106 0 7 theme -mediated 76:84 arg1 TLE 72:74 TLE 72:74 TLE 72:74 O-GlcNAc transferase is critical for transducin-like enhancer of split (TLE)-mediated repression of canonical Wnt signaling. 24616106 0 7 theme -mediated 76:84 arg1 repression 86:95 split (TLE)-mediated repression 65:95 split (TLE)-mediated repression of canonical Wnt signaling 65:122 O-GlcNAc transferase is critical for transducin-like enhancer of split (TLE)-mediated repression of canonical Wnt signaling. 24616106 0 8 theme canonical 100:108 arg1 signaling 114:122 canonical Wnt signaling 100:122 canonical Wnt signaling 100:122 O-GlcNAc transferase is critical for transducin-like enhancer of split (TLE)-mediated repression of canonical Wnt signaling. 24616106 4 9 from promoters 833:841 arg1 activation 802:811 gene activation 797:811 gene activation from Wnt-responsive promoters 797:841 Removal of O-GlcNAc from Wnt-responsive gene promoters is critical for gene activation from Wnt-responsive promoters. 24616106 3 10 theme O-GlcNAc 545:552 arg1 transferase 554:564 O-GlcNAc transferase 545:564 O-GlcNAc transferase 545:564 We report that association of TLEs with O-GlcNAc transferase, an enzyme that catalyzes posttranslational modification of proteins by O-linked N-acetylglucosamine, is essential for TLE-mediated transcriptional repression. 24616106 3 10 theme O-GlcNAc 545:552 arg1 enzyme 570:575 an enzyme 567:575 an enzyme that catalyzes posttranslational modification of proteins by O-linked N-acetylglucosamine 567:665 We report that association of TLEs with O-GlcNAc transferase, an enzyme that catalyzes posttranslational modification of proteins by O-linked N-acetylglucosamine, is essential for TLE-mediated transcriptional repression. 24616106 2 11 theme pathway-specific 393:408 arg1 factors 424:430 pathway-specific transcription factors 393:430 pathway-specific transcription factors 393:430 Although it is known that Groucho/TLEs are recruited to target genes by pathway-specific transcription factors, molecular events after the corepressor recruitment are largely unclear. 24616106 5 12 theme molecular 875:883 arg1 mechanism 885:893 a molecular mechanism 873:893 a molecular mechanism by which Groucho/TLEs repress gene transcription 873:942 Thus, these studies identify a molecular mechanism by which Groucho/TLEs repress gene transcription and provide a model whereby O-GlcNAc may control distinct intracellular signaling pathways. 24616106 1 13 theme mammalian 164:172 arg1 orthologues 174:184 its mammalian orthologues 160:184 its mammalian orthologues 160:184 The Drosophila Groucho protein and its mammalian orthologues the transducin-like enhancers of split (TLEs) are critical transcriptional corepressors that repress Wnt and other signaling pathways. 24616106 1 13 theme mammalian 164:172 arg1 protein 148:154 The Drosophila Groucho protein 125:154 The Drosophila Groucho protein 125:154 The Drosophila Groucho protein and its mammalian orthologues the transducin-like enhancers of split (TLEs) are critical transcriptional corepressors that repress Wnt and other signaling pathways. 24616106 1 13 theme mammalian 164:172 arg1 corepressors 261:272 critical transcriptional corepressors 236:272 critical transcriptional corepressors that repress Wnt and other signaling pathways 236:318 The Drosophila Groucho protein and its mammalian orthologues the transducin-like enhancers of split (TLEs) are critical transcriptional corepressors that repress Wnt and other signaling pathways. 24616106 2 14 theme corepressor 460:470 arg1 recruitment 472:482 the corepressor recruitment 456:482 the corepressor recruitment 456:482 Although it is known that Groucho/TLEs are recruited to target genes by pathway-specific transcription factors, molecular events after the corepressor recruitment are largely unclear. 24616106 1 15 dep protein 148:154 arg1 enhancers 206:214 the transducin-like enhancers 186:214 the transducin-like enhancers of split (TLEs) 186:230 The Drosophila Groucho protein and its mammalian orthologues the transducin-like enhancers of split (TLEs) are critical transcriptional corepressors that repress Wnt and other signaling pathways. 24616106 0 16 theme O-GlcNAc 0:7 arg1 transferase 9:19 O-GlcNAc transferase 0:19 O-GlcNAc transferase 0:19 O-GlcNAc transferase is critical for transducin-like enhancer of split (TLE)-mediated repression of canonical Wnt signaling. 24616106 3 17 theme posttranslational 592:608 arg1 modification 610:621 posttranslational modification 592:621 posttranslational modification of proteins by O-linked N-acetylglucosamine 592:665 We report that association of TLEs with O-GlcNAc transferase, an enzyme that catalyzes posttranslational modification of proteins by O-linked N-acetylglucosamine, is essential for TLE-mediated transcriptional repression. 24616106 2 18 theme target 377:382 arg1 genes 384:388 target genes 377:388 target genes 377:388 Although it is known that Groucho/TLEs are recruited to target genes by pathway-specific transcription factors, molecular events after the corepressor recruitment are largely unclear. 24616106 1 19 theme Wnt 287:289 arg1 pathways 311:318 Wnt and other signaling pathways 287:318 pathways 311:318 The Drosophila Groucho protein and its mammalian orthologues the transducin-like enhancers of split (TLEs) are critical transcriptional corepressors that repress Wnt and other signaling pathways. 24616106 0 20 theme signaling 114:122 arg1 TLE 72:74 TLE 72:74 TLE 72:74 O-GlcNAc transferase is critical for transducin-like enhancer of split (TLE)-mediated repression of canonical Wnt signaling. 24616106 0 20 theme signaling 114:122 arg1 repression 86:95 split (TLE)-mediated repression 65:95 split (TLE)-mediated repression of canonical Wnt signaling 65:122 O-GlcNAc transferase is critical for transducin-like enhancer of split (TLE)-mediated repression of canonical Wnt signaling. 24616106 4 21 theme Wnt-responsive 818:831 arg1 promoters 833:841 Wnt-responsive promoters 818:841 Wnt-responsive promoters 818:841 Removal of O-GlcNAc from Wnt-responsive gene promoters is critical for gene activation from Wnt-responsive promoters. 24616106 1 22 theme transducin-like 190:204 arg1 enhancers 206:214 the transducin-like enhancers 186:214 the transducin-like enhancers of split (TLEs) 186:230 The Drosophila Groucho protein and its mammalian orthologues the transducin-like enhancers of split (TLEs) are critical transcriptional corepressors that repress Wnt and other signaling pathways. 24616106 4 23 theme gene 797:800 arg1 activation 802:811 gene activation 797:811 gene activation from Wnt-responsive promoters 797:841 Removal of O-GlcNAc from Wnt-responsive gene promoters is critical for gene activation from Wnt-responsive promoters. 24616106 0 24 theme Wnt 110:112 arg1 signaling 114:122 canonical Wnt signaling 100:122 canonical Wnt signaling 100:122 O-GlcNAc transferase is critical for transducin-like enhancer of split (TLE)-mediated repression of canonical Wnt signaling. 24616106 3 25 theme TLE-mediated 685:696 arg1 repression 714:723 TLE-mediated transcriptional repression 685:723 TLE-mediated transcriptional repression 685:723 We report that association of TLEs with O-GlcNAc transferase, an enzyme that catalyzes posttranslational modification of proteins by O-linked N-acetylglucosamine, is essential for TLE-mediated transcriptional repression. 24616106 3 26 theme TLEs 535:538 arg1 association 520:530 association 520:530 association of TLEs with O-GlcNAc transferase, an enzyme that catalyzes posttranslational modification of proteins by O-linked N-acetylglucosamine, 520:666 We report that association of TLEs with O-GlcNAc transferase, an enzyme that catalyzes posttranslational modification of proteins by O-linked N-acetylglucosamine, is essential for TLE-mediated transcriptional repression. 24616106 0 27 theme transducin-like 37:51 arg1 enhancer 53:60 transducin-like enhancer 37:60 transducin-like enhancer of split (TLE)-mediated repression of canonical Wnt signaling 37:122 O-GlcNAc transferase is critical for transducin-like enhancer of split (TLE)-mediated repression of canonical Wnt signaling. 24616106 1 28 theme other 295:299 arg1 pathways 311:318 Wnt and other signaling pathways 287:318 pathways 311:318 The Drosophila Groucho protein and its mammalian orthologues the transducin-like enhancers of split (TLEs) are critical transcriptional corepressors that repress Wnt and other signaling pathways. 24616106 3 29 theme transcriptional 698:712 arg1 repression 714:723 TLE-mediated transcriptional repression 685:723 TLE-mediated transcriptional repression 685:723 We report that association of TLEs with O-GlcNAc transferase, an enzyme that catalyzes posttranslational modification of proteins by O-linked N-acetylglucosamine, is essential for TLE-mediated transcriptional repression. 24616106 3 30 theme proteins 626:633 arg1 modification 610:621 posttranslational modification 592:621 posttranslational modification of proteins by O-linked N-acetylglucosamine 592:665 We report that association of TLEs with O-GlcNAc transferase, an enzyme that catalyzes posttranslational modification of proteins by O-linked N-acetylglucosamine, is essential for TLE-mediated transcriptional repression. 24616106 5 31 theme gene 925:928 arg1 transcription 930:942 gene transcription 925:942 gene transcription 925:942 Thus, these studies identify a molecular mechanism by which Groucho/TLEs repress gene transcription and provide a model whereby O-GlcNAc may control distinct intracellular signaling pathways. 24616106 1 32 theme signaling 301:309 arg1 pathways 311:318 Wnt and other signaling pathways 287:318 pathways 311:318 The Drosophila Groucho protein and its mammalian orthologues the transducin-like enhancers of split (TLEs) are critical transcriptional corepressors that repress Wnt and other signaling pathways. 24616106 2 33 theme transcription 410:422 arg1 factors 424:430 pathway-specific transcription factors 393:430 pathway-specific transcription factors 393:430 Although it is known that Groucho/TLEs are recruited to target genes by pathway-specific transcription factors, molecular events after the corepressor recruitment are largely unclear. 24616106 5 34 theme distinct 993:1000 arg1 pathways 1026:1033 distinct intracellular signaling pathways 993:1033 distinct intracellular signaling pathways 993:1033 Thus, these studies identify a molecular mechanism by which Groucho/TLEs repress gene transcription and provide a model whereby O-GlcNAc may control distinct intracellular signaling pathways. 24616106 5 35 theme intracellular 1002:1014 arg1 pathways 1026:1033 distinct intracellular signaling pathways 993:1033 distinct intracellular signaling pathways 993:1033 Thus, these studies identify a molecular mechanism by which Groucho/TLEs repress gene transcription and provide a model whereby O-GlcNAc may control distinct intracellular signaling pathways. 24616106 5 36 theme signaling 1016:1024 arg1 pathways 1026:1033 distinct intracellular signaling pathways 993:1033 distinct intracellular signaling pathways 993:1033 Thus, these studies identify a molecular mechanism by which Groucho/TLEs repress gene transcription and provide a model whereby O-GlcNAc may control distinct intracellular signaling pathways. 24616106 4 37 theme O-GlcNAc 737:744 arg1 Removal 726:732 Removal 726:732 Removal of O-GlcNAc from Wnt-responsive gene promoters 726:779 Removal of O-GlcNAc from Wnt-responsive gene promoters is critical for gene activation from Wnt-responsive promoters. 24616106 1 38 theme split 219:223 arg1 enhancers 206:214 the transducin-like enhancers 186:214 the transducin-like enhancers of split (TLEs) 186:230 The Drosophila Groucho protein and its mammalian orthologues the transducin-like enhancers of split (TLEs) are critical transcriptional corepressors that repress Wnt and other signaling pathways. 24616106 3 39 theme O-linked 638:645 arg1 N-acetylglucosamine 647:665 O-linked N-acetylglucosamine 638:665 O-linked N-acetylglucosamine 638:665 We report that association of TLEs with O-GlcNAc transferase, an enzyme that catalyzes posttranslational modification of proteins by O-linked N-acetylglucosamine, is essential for TLE-mediated transcriptional repression. 24616106 2 40 theme molecular 433:441 arg1 events 443:448 molecular events 433:448 molecular events after the corepressor recruitment 433:482 Although it is known that Groucho/TLEs are recruited to target genes by pathway-specific transcription factors, molecular events after the corepressor recruitment are largely unclear. 24616106 1 41 theme Drosophila 129:138 arg1 orthologues 174:184 its mammalian orthologues 160:184 its mammalian orthologues 160:184 The Drosophila Groucho protein and its mammalian orthologues the transducin-like enhancers of split (TLEs) are critical transcriptional corepressors that repress Wnt and other signaling pathways. 24616106 1 41 theme Drosophila 129:138 arg1 corepressors 261:272 critical transcriptional corepressors 236:272 critical transcriptional corepressors that repress Wnt and other signaling pathways 236:318 The Drosophila Groucho protein and its mammalian orthologues the transducin-like enhancers of split (TLEs) are critical transcriptional corepressors that repress Wnt and other signaling pathways. 24616106 1 41 theme Drosophila 129:138 arg1 protein 148:154 The Drosophila Groucho protein 125:154 The Drosophila Groucho protein 125:154 The Drosophila Groucho protein and its mammalian orthologues the transducin-like enhancers of split (TLEs) are critical transcriptional corepressors that repress Wnt and other signaling pathways. 24616106 4 42 from promoters 771:779 arg1 Removal 726:732 Removal 726:732 Removal of O-GlcNAc from Wnt-responsive gene promoters 726:779 Removal of O-GlcNAc from Wnt-responsive gene promoters is critical for gene activation from Wnt-responsive promoters. 24616106 0 43 theme split 65:69 arg1 TLE 72:74 TLE 72:74 TLE 72:74 O-GlcNAc transferase is critical for transducin-like enhancer of split (TLE)-mediated repression of canonical Wnt signaling. 24616106 0 43 theme split 65:69 arg1 repression 86:95 split (TLE)-mediated repression 65:95 split (TLE)-mediated repression of canonical Wnt signaling 65:122 O-GlcNAc transferase is critical for transducin-like enhancer of split (TLE)-mediated repression of canonical Wnt signaling. 24616106 1 44 theme Groucho 140:146 arg1 orthologues 174:184 its mammalian orthologues 160:184 its mammalian orthologues 160:184 The Drosophila Groucho protein and its mammalian orthologues the transducin-like enhancers of split (TLEs) are critical transcriptional corepressors that repress Wnt and other signaling pathways. 24616106 1 44 theme Groucho 140:146 arg1 corepressors 261:272 critical transcriptional corepressors 236:272 critical transcriptional corepressors that repress Wnt and other signaling pathways 236:318 The Drosophila Groucho protein and its mammalian orthologues the transducin-like enhancers of split (TLEs) are critical transcriptional corepressors that repress Wnt and other signaling pathways. 24616106 1 44 theme Groucho 140:146 arg1 protein 148:154 The Drosophila Groucho protein 125:154 The Drosophila Groucho protein 125:154 The Drosophila Groucho protein and its mammalian orthologues the transducin-like enhancers of split (TLEs) are critical transcriptional corepressors that repress Wnt and other signaling pathways. 28154133 7 0 theme many 1292:1295 arg1 pathways 1317:1324 many cellular regulation pathways 1292:1324 many cellular regulation pathways 1292:1324 Our study generates a snapshot of the O-GlcNAc modification landscape in plants, indicating functions in many cellular regulation pathways and providing a powerful resource for further dissecting these functions at the molecular level. 28154133 7 1 from plants 1260:1265 arg1 snapshot 1209:1216 a snapshot 1207:1216 a snapshot of the O-GlcNAc modification landscape in plants 1207:1265 Our study generates a snapshot of the O-GlcNAc modification landscape in plants, indicating functions in many cellular regulation pathways and providing a powerful resource for further dissecting these functions at the molecular level. 28154133 3 2 theme mass 539:542 arg1 spectrometry 544:555 mass spectrometry 539:555 mass spectrometry 539:555 Here, we report a large-scale proteomic identification of O-GlcNAc-modified proteins and sites in the model plant Arabidopsis thaliana Using lectin weak affinity chromatography to enrich modified peptides, followed by mass spectrometry, we identified 971 O-GlcNAc-modified peptides belonging to 262 proteins. 28154133 5 3 theme physiological 840:852 arg1 processes 854:862 developmental and physiological processes 822:862 developmental and physiological processes 822:862 Many proteins have functions in developmental and physiological processes specific to plants, such as hormone responses and flower development. 28154133 5 3 theme physiological 840:852 arg1 development 921:931 flower development 914:931 flower development 914:931 Many proteins have functions in developmental and physiological processes specific to plants, such as hormone responses and flower development. 28154133 5 3 theme physiological 840:852 arg1 responses 900:908 hormone responses 892:908 hormone responses 892:908 Many proteins have functions in developmental and physiological processes specific to plants, such as hormone responses and flower development. 28154133 6 4 theme modifications 1134:1146 arg1 cooccurrence 1110:1121 cooccurrence 1110:1121 cooccurrence of the two modifications in the same peptide molecule 1110:1175 Mass spectrometric analysis of phosphopeptides from the same samples showed that a large number of peptides could be modified by either O-GlcNAcylation or phosphorylation, but cooccurrence of the two modifications in the same peptide molecule was rare. 28154133 3 5 dep sites 410:414 arg1 identified 561:570 identified 561:570 identified 971 O-GlcNAc-modified peptides belonging to 262 proteins 561:627 Here, we report a large-scale proteomic identification of O-GlcNAc-modified proteins and sites in the model plant Arabidopsis thaliana Using lectin weak affinity chromatography to enrich modified peptides, followed by mass spectrometry, we identified 971 O-GlcNAc-modified peptides belonging to 262 proteins. 28154133 3 6 from proteins 397:404 arg1 thaliana 447:454 the model plant Arabidopsis thaliana 419:454 the model plant Arabidopsis thaliana 419:454 Here, we report a large-scale proteomic identification of O-GlcNAc-modified proteins and sites in the model plant Arabidopsis thaliana Using lectin weak affinity chromatography to enrich modified peptides, followed by mass spectrometry, we identified 971 O-GlcNAc-modified peptides belonging to 262 proteins. 28154133 6 7 from samples 995:1001 arg1 phosphopeptides 965:979 phosphopeptides 965:979 phosphopeptides from the same samples 965:1001 Mass spectrometric analysis of phosphopeptides from the same samples showed that a large number of peptides could be modified by either O-GlcNAcylation or phosphorylation, but cooccurrence of the two modifications in the same peptide molecule was rare. 28154133 6 7 from samples 995:1001 arg1 analysis 953:960 Mass spectrometric analysis 934:960 Mass spectrometric analysis of phosphopeptides from the same samples 934:1001 Mass spectrometric analysis of phosphopeptides from the same samples showed that a large number of peptides could be modified by either O-GlcNAcylation or phosphorylation, but cooccurrence of the two modifications in the same peptide molecule was rare. 28154133 3 8 theme O-GlcNAc-modified 379:395 arg1 proteins 397:404 O-GlcNAc-modified proteins 379:404 O-GlcNAc-modified proteins 379:404 Here, we report a large-scale proteomic identification of O-GlcNAc-modified proteins and sites in the model plant Arabidopsis thaliana Using lectin weak affinity chromatography to enrich modified peptides, followed by mass spectrometry, we identified 971 O-GlcNAc-modified peptides belonging to 262 proteins. 28154133 3 9 from thaliana 447:454 arg1 identification 361:374 a large-scale proteomic identification 337:374 a large-scale proteomic identification of O-GlcNAc-modified proteins and sites in the model plant Arabidopsis thaliana Using lectin weak affinity chromatography to enrich modified peptides, followed by mass spectrometry, we identified 971 O-GlcNAc-modified peptides belonging to 262 proteins 337:627 Here, we report a large-scale proteomic identification of O-GlcNAc-modified proteins and sites in the model plant Arabidopsis thaliana Using lectin weak affinity chromatography to enrich modified peptides, followed by mass spectrometry, we identified 971 O-GlcNAc-modified peptides belonging to 262 proteins. 28154133 6 10 from cooccurrence 1110:1121 arg1 molecule 1168:1175 the same peptide molecule 1151:1175 the same peptide molecule 1151:1175 Mass spectrometric analysis of phosphopeptides from the same samples showed that a large number of peptides could be modified by either O-GlcNAcylation or phosphorylation, but cooccurrence of the two modifications in the same peptide molecule was rare. 28154133 6 11 theme spectrometric 939:951 arg1 analysis 953:960 Mass spectrometric analysis 934:960 Mass spectrometric analysis of phosphopeptides from the same samples 934:1001 Mass spectrometric analysis of phosphopeptides from the same samples showed that a large number of peptides could be modified by either O-GlcNAcylation or phosphorylation, but cooccurrence of the two modifications in the same peptide molecule was rare. 28154133 3 12 theme O-GlcNAc-modified 576:592 arg1 peptides 594:601 971 O-GlcNAc-modified peptides 572:601 971 O-GlcNAc-modified peptides belonging to 262 proteins 572:627 Here, we report a large-scale proteomic identification of O-GlcNAc-modified proteins and sites in the model plant Arabidopsis thaliana Using lectin weak affinity chromatography to enrich modified peptides, followed by mass spectrometry, we identified 971 O-GlcNAc-modified peptides belonging to 262 proteins. 28154133 6 13 from molecule 1168:1175 arg1 cooccurrence 1110:1121 cooccurrence 1110:1121 cooccurrence of the two modifications in the same peptide molecule 1110:1175 Mass spectrometric analysis of phosphopeptides from the same samples showed that a large number of peptides could be modified by either O-GlcNAcylation or phosphorylation, but cooccurrence of the two modifications in the same peptide molecule was rare. 28154133 3 14 theme proteins 397:404 arg1 identification 361:374 a large-scale proteomic identification 337:374 a large-scale proteomic identification of O-GlcNAc-modified proteins and sites in the model plant Arabidopsis thaliana Using lectin weak affinity chromatography to enrich modified peptides, followed by mass spectrometry, we identified 971 O-GlcNAc-modified peptides belonging to 262 proteins 337:627 Here, we report a large-scale proteomic identification of O-GlcNAc-modified proteins and sites in the model plant Arabidopsis thaliana Using lectin weak affinity chromatography to enrich modified peptides, followed by mass spectrometry, we identified 971 O-GlcNAc-modified peptides belonging to 262 proteins. 28154133 6 15 theme same 990:993 arg1 samples 995:1001 the same samples 986:1001 the same samples 986:1001 Mass spectrometric analysis of phosphopeptides from the same samples showed that a large number of peptides could be modified by either O-GlcNAcylation or phosphorylation, but cooccurrence of the two modifications in the same peptide molecule was rare. 28154133 7 16 theme cellular 1297:1304 arg1 pathways 1317:1324 many cellular regulation pathways 1292:1324 many cellular regulation pathways 1292:1324 Our study generates a snapshot of the O-GlcNAc modification landscape in plants, indicating functions in many cellular regulation pathways and providing a powerful resource for further dissecting these functions at the molecular level. 28154133 1 17 theme N-acetylglucosamine 166:184 arg1 modification 197:208 O-linked N-acetylglucosamine (O-GlcNAc) modification 157:208 O-linked N-acetylglucosamine (O-GlcNAc) modification in plants 157:218 Genetic studies have shown essential functions of O-linked N-acetylglucosamine (O-GlcNAc) modification in plants. 28154133 4 18 theme modified 634:641 arg1 proteins 643:650 The modified proteins 630:650 The modified proteins 630:650 The modified proteins are involved in cellular regulatory processes, including transcription, translation, epigenetic gene regulation, and signal transduction. 28154133 3 19 from sites 410:414 arg1 thaliana 447:454 the model plant Arabidopsis thaliana 419:454 the model plant Arabidopsis thaliana 419:454 Here, we report a large-scale proteomic identification of O-GlcNAc-modified proteins and sites in the model plant Arabidopsis thaliana Using lectin weak affinity chromatography to enrich modified peptides, followed by mass spectrometry, we identified 971 O-GlcNAc-modified peptides belonging to 262 proteins. 28154133 7 20 theme landscape 1247:1255 arg1 snapshot 1209:1216 a snapshot 1207:1216 a snapshot of the O-GlcNAc modification landscape in plants 1207:1265 Our study generates a snapshot of the O-GlcNAc modification landscape in plants, indicating functions in many cellular regulation pathways and providing a powerful resource for further dissecting these functions at the molecular level. 28154133 4 21 theme regulatory 677:686 arg1 regulation 753:762 epigenetic gene regulation 737:762 epigenetic gene regulation 737:762 The modified proteins are involved in cellular regulatory processes, including transcription, translation, epigenetic gene regulation, and signal transduction. 28154133 4 21 theme regulatory 677:686 arg1 translation 724:734 translation 724:734 translation 724:734 The modified proteins are involved in cellular regulatory processes, including transcription, translation, epigenetic gene regulation, and signal transduction. 28154133 4 21 theme regulatory 677:686 arg1 transduction 776:787 signal transduction 769:787 signal transduction 769:787 The modified proteins are involved in cellular regulatory processes, including transcription, translation, epigenetic gene regulation, and signal transduction. 28154133 4 21 theme regulatory 677:686 arg1 processes 688:696 cellular regulatory processes 668:696 cellular regulatory processes 668:696 The modified proteins are involved in cellular regulatory processes, including transcription, translation, epigenetic gene regulation, and signal transduction. 28154133 4 21 theme regulatory 677:686 arg1 transcription 709:721 transcription 709:721 transcription 709:721 The modified proteins are involved in cellular regulatory processes, including transcription, translation, epigenetic gene regulation, and signal transduction. 28154133 7 22 theme molecular 1406:1414 arg1 level 1416:1420 the molecular level 1402:1420 the molecular level 1402:1420 Our study generates a snapshot of the O-GlcNAc modification landscape in plants, indicating functions in many cellular regulation pathways and providing a powerful resource for further dissecting these functions at the molecular level. 28154133 3 23 theme weak 469:472 arg1 chromatography 483:496 lectin weak affinity chromatography 462:496 lectin weak affinity chromatography 462:496 Here, we report a large-scale proteomic identification of O-GlcNAc-modified proteins and sites in the model plant Arabidopsis thaliana Using lectin weak affinity chromatography to enrich modified peptides, followed by mass spectrometry, we identified 971 O-GlcNAc-modified peptides belonging to 262 proteins. 28154133 6 24 theme phosphopeptides 965:979 arg1 analysis 953:960 Mass spectrometric analysis 934:960 Mass spectrometric analysis of phosphopeptides from the same samples 934:1001 Mass spectrometric analysis of phosphopeptides from the same samples showed that a large number of peptides could be modified by either O-GlcNAcylation or phosphorylation, but cooccurrence of the two modifications in the same peptide molecule was rare. 28154133 3 25 theme large-scale 339:349 arg1 identification 361:374 a large-scale proteomic identification 337:374 a large-scale proteomic identification of O-GlcNAc-modified proteins and sites in the model plant Arabidopsis thaliana Using lectin weak affinity chromatography to enrich modified peptides, followed by mass spectrometry, we identified 971 O-GlcNAc-modified peptides belonging to 262 proteins 337:627 Here, we report a large-scale proteomic identification of O-GlcNAc-modified proteins and sites in the model plant Arabidopsis thaliana Using lectin weak affinity chromatography to enrich modified peptides, followed by mass spectrometry, we identified 971 O-GlcNAc-modified peptides belonging to 262 proteins. 28154133 7 26 from landscape 1247:1255 arg1 plants 1260:1265 plants 1260:1265 plants 1260:1265 Our study generates a snapshot of the O-GlcNAc modification landscape in plants, indicating functions in many cellular regulation pathways and providing a powerful resource for further dissecting these functions at the molecular level. 28154133 3 27 theme affinity 474:481 arg1 chromatography 483:496 lectin weak affinity chromatography 462:496 lectin weak affinity chromatography 462:496 Here, we report a large-scale proteomic identification of O-GlcNAc-modified proteins and sites in the model plant Arabidopsis thaliana Using lectin weak affinity chromatography to enrich modified peptides, followed by mass spectrometry, we identified 971 O-GlcNAc-modified peptides belonging to 262 proteins. 28154133 6 28 mod modified 1051:1058 arg1 number 1023:1028 a large number 1015:1028 a large number of peptides 1015:1040 Mass spectrometric analysis of phosphopeptides from the same samples showed that a large number of peptides could be modified by either O-GlcNAcylation or phosphorylation, but cooccurrence of the two modifications in the same peptide molecule was rare. 28154133 6 28 mod modified 1051:1058 arg3 O-GlcNAcylation 1070:1084 O-GlcNAcylation 1070:1084 O-GlcNAcylation 1070:1084 Mass spectrometric analysis of phosphopeptides from the same samples showed that a large number of peptides could be modified by either O-GlcNAcylation or phosphorylation, but cooccurrence of the two modifications in the same peptide molecule was rare. 28154133 6 28 mod modified 1051:1058 arg3 phosphorylation 1089:1103 phosphorylation 1089:1103 phosphorylation 1089:1103 Mass spectrometric analysis of phosphopeptides from the same samples showed that a large number of peptides could be modified by either O-GlcNAcylation or phosphorylation, but cooccurrence of the two modifications in the same peptide molecule was rare. 28154133 6 29 theme peptide 1160:1166 arg1 molecule 1168:1175 the same peptide molecule 1151:1175 the same peptide molecule 1151:1175 Mass spectrometric analysis of phosphopeptides from the same samples showed that a large number of peptides could be modified by either O-GlcNAcylation or phosphorylation, but cooccurrence of the two modifications in the same peptide molecule was rare. 28154133 1 30 from functions 144:152 arg1 plants 213:218 plants 213:218 plants 213:218 Genetic studies have shown essential functions of O-linked N-acetylglucosamine (O-GlcNAc) modification in plants. 28154133 3 31 theme 262 616:618 arg1 proteins 620:627 262 proteins 616:627 262 proteins 616:627 Here, we report a large-scale proteomic identification of O-GlcNAc-modified proteins and sites in the model plant Arabidopsis thaliana Using lectin weak affinity chromatography to enrich modified peptides, followed by mass spectrometry, we identified 971 O-GlcNAc-modified peptides belonging to 262 proteins. 28154133 5 32 contain have 804:807 arg2 functions 809:817 functions 809:817 functions 809:817 Many proteins have functions in developmental and physiological processes specific to plants, such as hormone responses and flower development. 28154133 5 32 contain have 804:807 arg1 proteins 795:802 Many proteins 790:802 Many proteins 790:802 Many proteins have functions in developmental and physiological processes specific to plants, such as hormone responses and flower development. 28154133 1 33 theme modification 197:208 arg1 functions 144:152 essential functions 134:152 essential functions of O-linked N-acetylglucosamine (O-GlcNAc) modification in plants 134:218 Genetic studies have shown essential functions of O-linked N-acetylglucosamine (O-GlcNAc) modification in plants. 28154133 0 34 theme Proteomic 0:8 arg1 analysis 10:17 Proteomic analysis 0:17 Proteomic analysis 0:17 Proteomic analysis reveals O-GlcNAc modification on proteins with key regulatory functions in Arabidopsis. 28154133 7 35 theme O-GlcNAc 1225:1232 arg1 modification 1234:1245 O-GlcNAc modification 1225:1245 the O-GlcNAc modification landscape in plants 1221:1265 Our study generates a snapshot of the O-GlcNAc modification landscape in plants, indicating functions in many cellular regulation pathways and providing a powerful resource for further dissecting these functions at the molecular level. 28154133 6 36 from modifications 1134:1146 arg1 molecule 1168:1175 the same peptide molecule 1151:1175 the same peptide molecule 1151:1175 Mass spectrometric analysis of phosphopeptides from the same samples showed that a large number of peptides could be modified by either O-GlcNAcylation or phosphorylation, but cooccurrence of the two modifications in the same peptide molecule was rare. 28154133 3 37 theme lectin 462:467 arg1 chromatography 483:496 lectin weak affinity chromatography 462:496 lectin weak affinity chromatography 462:496 Here, we report a large-scale proteomic identification of O-GlcNAc-modified proteins and sites in the model plant Arabidopsis thaliana Using lectin weak affinity chromatography to enrich modified peptides, followed by mass spectrometry, we identified 971 O-GlcNAc-modified peptides belonging to 262 proteins. 28154133 0 38 theme O-GlcNAc 27:34 arg1 modification 36:47 O-GlcNAc modification 27:47 O-GlcNAc modification 27:47 Proteomic analysis reveals O-GlcNAc modification on proteins with key regulatory functions in Arabidopsis. 28154133 1 39 theme Genetic 107:113 arg1 studies 115:121 Genetic studies 107:121 Genetic studies 107:121 Genetic studies have shown essential functions of O-linked N-acetylglucosamine (O-GlcNAc) modification in plants. 28154133 2 40 dep proteins 234:241 arg1 the 230:232 the 230:232 the 230:232 However, the proteins and sites subject to this posttranslational modification are largely unknown. 28154133 3 41 theme sites 410:414 arg1 identification 361:374 a large-scale proteomic identification 337:374 a large-scale proteomic identification of O-GlcNAc-modified proteins and sites in the model plant Arabidopsis thaliana Using lectin weak affinity chromatography to enrich modified peptides, followed by mass spectrometry, we identified 971 O-GlcNAc-modified peptides belonging to 262 proteins 337:627 Here, we report a large-scale proteomic identification of O-GlcNAc-modified proteins and sites in the model plant Arabidopsis thaliana Using lectin weak affinity chromatography to enrich modified peptides, followed by mass spectrometry, we identified 971 O-GlcNAc-modified peptides belonging to 262 proteins. 28154133 3 42 from identification 361:374 arg1 thaliana 447:454 the model plant Arabidopsis thaliana 419:454 the model plant Arabidopsis thaliana 419:454 Here, we report a large-scale proteomic identification of O-GlcNAc-modified proteins and sites in the model plant Arabidopsis thaliana Using lectin weak affinity chromatography to enrich modified peptides, followed by mass spectrometry, we identified 971 O-GlcNAc-modified peptides belonging to 262 proteins. 28154133 3 43 theme modified 508:515 arg1 peptides 517:524 modified peptides 508:524 modified peptides 508:524 Here, we report a large-scale proteomic identification of O-GlcNAc-modified proteins and sites in the model plant Arabidopsis thaliana Using lectin weak affinity chromatography to enrich modified peptides, followed by mass spectrometry, we identified 971 O-GlcNAc-modified peptides belonging to 262 proteins. 28154133 3 44 theme Arabidopsis 435:445 arg1 thaliana 447:454 the model plant Arabidopsis thaliana 419:454 the model plant Arabidopsis thaliana 419:454 Here, we report a large-scale proteomic identification of O-GlcNAc-modified proteins and sites in the model plant Arabidopsis thaliana Using lectin weak affinity chromatography to enrich modified peptides, followed by mass spectrometry, we identified 971 O-GlcNAc-modified peptides belonging to 262 proteins. 28154133 6 45 theme peptides 1033:1040 arg1 number 1023:1028 a large number 1015:1028 a large number of peptides 1015:1040 Mass spectrometric analysis of phosphopeptides from the same samples showed that a large number of peptides could be modified by either O-GlcNAcylation or phosphorylation, but cooccurrence of the two modifications in the same peptide molecule was rare. 28154133 0 46 from functions 81:89 arg1 Arabidopsis 94:104 Arabidopsis 94:104 Arabidopsis 94:104 Proteomic analysis reveals O-GlcNAc modification on proteins with key regulatory functions in Arabidopsis. 28154133 3 47 dep Using 456:460 arg1 followed 527:534 followed 527:534 followed by mass spectrometry 527:555 Here, we report a large-scale proteomic identification of O-GlcNAc-modified proteins and sites in the model plant Arabidopsis thaliana Using lectin weak affinity chromatography to enrich modified peptides, followed by mass spectrometry, we identified 971 O-GlcNAc-modified peptides belonging to 262 proteins. 28154133 5 48 theme flower 914:919 arg1 development 921:931 flower development 914:931 flower development 914:931 Many proteins have functions in developmental and physiological processes specific to plants, such as hormone responses and flower development. 28154133 5 49 theme specific 864:871 arg1 processes 854:862 developmental and physiological processes 822:862 developmental and physiological processes 822:862 Many proteins have functions in developmental and physiological processes specific to plants, such as hormone responses and flower development. 28154133 5 49 theme specific 864:871 arg1 development 921:931 flower development 914:931 flower development 914:931 Many proteins have functions in developmental and physiological processes specific to plants, such as hormone responses and flower development. 28154133 5 49 theme specific 864:871 arg1 responses 900:908 hormone responses 892:908 hormone responses 892:908 Many proteins have functions in developmental and physiological processes specific to plants, such as hormone responses and flower development. 28154133 1 50 link O-linked 157:164 arg1 O-GlcNAc 187:194 O-GlcNAc 187:194 O-GlcNAc 187:194 Genetic studies have shown essential functions of O-linked N-acetylglucosamine (O-GlcNAc) modification in plants. 28154133 1 50 link O-linked 157:164 arg1 N-acetylglucosamine 166:184 O-linked N-acetylglucosamine 157:184 O-linked N-acetylglucosamine (O-GlcNAc) modification in plants 157:218 Genetic studies have shown essential functions of O-linked N-acetylglucosamine (O-GlcNAc) modification in plants. 28154133 6 51 theme Mass 934:937 arg1 analysis 953:960 Mass spectrometric analysis 934:960 Mass spectrometric analysis of phosphopeptides from the same samples 934:1001 Mass spectrometric analysis of phosphopeptides from the same samples showed that a large number of peptides could be modified by either O-GlcNAcylation or phosphorylation, but cooccurrence of the two modifications in the same peptide molecule was rare. 28154133 6 52 from analysis 953:960 arg1 samples 995:1001 the same samples 986:1001 the same samples 986:1001 Mass spectrometric analysis of phosphopeptides from the same samples showed that a large number of peptides could be modified by either O-GlcNAcylation or phosphorylation, but cooccurrence of the two modifications in the same peptide molecule was rare. 28154133 7 53 dep generates 1197:1205 arg1 providing 1330:1338 providing 1330:1338 providing a powerful resource for further dissecting these functions at the molecular level 1330:1420 Our study generates a snapshot of the O-GlcNAc modification landscape in plants, indicating functions in many cellular regulation pathways and providing a powerful resource for further dissecting these functions at the molecular level. 28154133 7 53 dep generates 1197:1205 arg1 indicating 1268:1277 indicating 1268:1277 indicating functions in many cellular regulation pathways 1268:1324 Our study generates a snapshot of the O-GlcNAc modification landscape in plants, indicating functions in many cellular regulation pathways and providing a powerful resource for further dissecting these functions at the molecular level. 28154133 3 54 theme model 423:427 arg1 thaliana 447:454 the model plant Arabidopsis thaliana 419:454 the model plant Arabidopsis thaliana 419:454 Here, we report a large-scale proteomic identification of O-GlcNAc-modified proteins and sites in the model plant Arabidopsis thaliana Using lectin weak affinity chromatography to enrich modified peptides, followed by mass spectrometry, we identified 971 O-GlcNAc-modified peptides belonging to 262 proteins. 28154133 5 55 theme Many 790:793 arg1 proteins 795:802 Many proteins 790:802 Many proteins 790:802 Many proteins have functions in developmental and physiological processes specific to plants, such as hormone responses and flower development. 28154133 3 56 theme proteomic 351:359 arg1 identification 361:374 a large-scale proteomic identification 337:374 a large-scale proteomic identification of O-GlcNAc-modified proteins and sites in the model plant Arabidopsis thaliana Using lectin weak affinity chromatography to enrich modified peptides, followed by mass spectrometry, we identified 971 O-GlcNAc-modified peptides belonging to 262 proteins 337:627 Here, we report a large-scale proteomic identification of O-GlcNAc-modified proteins and sites in the model plant Arabidopsis thaliana Using lectin weak affinity chromatography to enrich modified peptides, followed by mass spectrometry, we identified 971 O-GlcNAc-modified peptides belonging to 262 proteins. 28154133 4 57 theme signal 769:774 arg1 transduction 776:787 signal transduction 769:787 signal transduction 769:787 The modified proteins are involved in cellular regulatory processes, including transcription, translation, epigenetic gene regulation, and signal transduction. 28154133 3 58 theme plant 429:433 arg1 thaliana 447:454 the model plant Arabidopsis thaliana 419:454 the model plant Arabidopsis thaliana 419:454 Here, we report a large-scale proteomic identification of O-GlcNAc-modified proteins and sites in the model plant Arabidopsis thaliana Using lectin weak affinity chromatography to enrich modified peptides, followed by mass spectrometry, we identified 971 O-GlcNAc-modified peptides belonging to 262 proteins. 28154133 6 59 theme large 1017:1021 arg1 number 1023:1028 a large number 1015:1028 a large number of peptides 1015:1040 Mass spectrometric analysis of phosphopeptides from the same samples showed that a large number of peptides could be modified by either O-GlcNAcylation or phosphorylation, but cooccurrence of the two modifications in the same peptide molecule was rare. 28154133 7 60 theme regulation 1306:1315 arg1 pathways 1317:1324 many cellular regulation pathways 1292:1324 many cellular regulation pathways 1292:1324 Our study generates a snapshot of the O-GlcNAc modification landscape in plants, indicating functions in many cellular regulation pathways and providing a powerful resource for further dissecting these functions at the molecular level. 28154133 1 61 from plants 213:218 arg1 functions 144:152 essential functions 134:152 essential functions of O-linked N-acetylglucosamine (O-GlcNAc) modification in plants 134:218 Genetic studies have shown essential functions of O-linked N-acetylglucosamine (O-GlcNAc) modification in plants. 28154133 7 62 from functions 1279:1287 arg1 pathways 1317:1324 many cellular regulation pathways 1292:1324 many cellular regulation pathways 1292:1324 Our study generates a snapshot of the O-GlcNAc modification landscape in plants, indicating functions in many cellular regulation pathways and providing a powerful resource for further dissecting these functions at the molecular level. 28154133 7 63 theme modification 1234:1245 arg1 landscape 1247:1255 the O-GlcNAc modification landscape 1221:1255 the O-GlcNAc modification landscape in plants 1221:1265 Our study generates a snapshot of the O-GlcNAc modification landscape in plants, indicating functions in many cellular regulation pathways and providing a powerful resource for further dissecting these functions at the molecular level. 28154133 2 64 theme posttranslational 269:285 arg1 modification 287:298 this posttranslational modification 264:298 this posttranslational modification 264:298 However, the proteins and sites subject to this posttranslational modification are largely unknown. 28154133 5 65 theme developmental 822:834 arg1 processes 854:862 developmental and physiological processes 822:862 developmental and physiological processes 822:862 Many proteins have functions in developmental and physiological processes specific to plants, such as hormone responses and flower development. 28154133 5 65 theme developmental 822:834 arg1 development 921:931 flower development 914:931 flower development 914:931 Many proteins have functions in developmental and physiological processes specific to plants, such as hormone responses and flower development. 28154133 5 65 theme developmental 822:834 arg1 responses 900:908 hormone responses 892:908 hormone responses 892:908 Many proteins have functions in developmental and physiological processes specific to plants, such as hormone responses and flower development. 28154133 1 66 theme essential 134:142 arg1 functions 144:152 essential functions 134:152 essential functions of O-linked N-acetylglucosamine (O-GlcNAc) modification in plants 134:218 Genetic studies have shown essential functions of O-linked N-acetylglucosamine (O-GlcNAc) modification in plants. 28154133 5 67 theme hormone 892:898 arg1 responses 900:908 hormone responses 892:908 hormone responses 892:908 Many proteins have functions in developmental and physiological processes specific to plants, such as hormone responses and flower development. 28154133 1 68 from modification 197:208 arg1 plants 213:218 plants 213:218 plants 213:218 Genetic studies have shown essential functions of O-linked N-acetylglucosamine (O-GlcNAc) modification in plants. 28154133 4 69 theme epigenetic 737:746 arg1 regulation 753:762 epigenetic gene regulation 737:762 epigenetic gene regulation 737:762 The modified proteins are involved in cellular regulatory processes, including transcription, translation, epigenetic gene regulation, and signal transduction. 28154133 7 70 theme powerful 1342:1349 arg1 resource 1351:1358 a powerful resource 1340:1358 a powerful resource for further dissecting these functions at the molecular level 1340:1420 Our study generates a snapshot of the O-GlcNAc modification landscape in plants, indicating functions in many cellular regulation pathways and providing a powerful resource for further dissecting these functions at the molecular level. 28154133 0 71 theme regulatory 70:79 arg1 functions 81:89 key regulatory functions 66:89 key regulatory functions in Arabidopsis 66:104 Proteomic analysis reveals O-GlcNAc modification on proteins with key regulatory functions in Arabidopsis. 28154133 0 72 with proteins 52:59 arg1 functions 81:89 key regulatory functions 66:89 key regulatory functions in Arabidopsis 66:104 Proteomic analysis reveals O-GlcNAc modification on proteins with key regulatory functions in Arabidopsis. 28154133 4 73 theme gene 748:751 arg1 regulation 753:762 epigenetic gene regulation 737:762 epigenetic gene regulation 737:762 The modified proteins are involved in cellular regulatory processes, including transcription, translation, epigenetic gene regulation, and signal transduction. 28154133 6 74 theme same 1155:1158 arg1 molecule 1168:1175 the same peptide molecule 1151:1175 the same peptide molecule 1151:1175 Mass spectrometric analysis of phosphopeptides from the same samples showed that a large number of peptides could be modified by either O-GlcNAcylation or phosphorylation, but cooccurrence of the two modifications in the same peptide molecule was rare. 28154133 4 75 theme cellular 668:675 arg1 regulation 753:762 epigenetic gene regulation 737:762 epigenetic gene regulation 737:762 The modified proteins are involved in cellular regulatory processes, including transcription, translation, epigenetic gene regulation, and signal transduction. 28154133 4 75 theme cellular 668:675 arg1 translation 724:734 translation 724:734 translation 724:734 The modified proteins are involved in cellular regulatory processes, including transcription, translation, epigenetic gene regulation, and signal transduction. 28154133 4 75 theme cellular 668:675 arg1 transduction 776:787 signal transduction 769:787 signal transduction 769:787 The modified proteins are involved in cellular regulatory processes, including transcription, translation, epigenetic gene regulation, and signal transduction. 28154133 4 75 theme cellular 668:675 arg1 processes 688:696 cellular regulatory processes 668:696 cellular regulatory processes 668:696 The modified proteins are involved in cellular regulatory processes, including transcription, translation, epigenetic gene regulation, and signal transduction. 28154133 4 75 theme cellular 668:675 arg1 transcription 709:721 transcription 709:721 transcription 709:721 The modified proteins are involved in cellular regulatory processes, including transcription, translation, epigenetic gene regulation, and signal transduction. 28154133 0 76 theme key 66:68 arg1 functions 81:89 key regulatory functions 66:89 key regulatory functions in Arabidopsis 66:104 Proteomic analysis reveals O-GlcNAc modification on proteins with key regulatory functions in Arabidopsis. 28154133 7 77 from snapshot 1209:1216 arg1 plants 1260:1265 plants 1260:1265 plants 1260:1265 Our study generates a snapshot of the O-GlcNAc modification landscape in plants, indicating functions in many cellular regulation pathways and providing a powerful resource for further dissecting these functions at the molecular level. 28154133 2 78 theme subject 253:259 arg1 proteins 234:241 proteins 234:241 proteins 234:241 However, the proteins and sites subject to this posttranslational modification are largely unknown. 28154133 1 79 theme O-linked 157:164 arg1 O-GlcNAc 187:194 O-GlcNAc 187:194 O-GlcNAc 187:194 Genetic studies have shown essential functions of O-linked N-acetylglucosamine (O-GlcNAc) modification in plants. 28154133 1 79 theme O-linked 157:164 arg1 N-acetylglucosamine 166:184 O-linked N-acetylglucosamine 157:184 O-linked N-acetylglucosamine (O-GlcNAc) modification in plants 157:218 Genetic studies have shown essential functions of O-linked N-acetylglucosamine (O-GlcNAc) modification in plants. 28038474 0 0 theme myocardial 88:97 arg1 injury 120:125 myocardial ischemia/reperfusion injury 88:125 myocardial ischemia/reperfusion injury 88:125 Inhibition of ALDH2 by O-GlcNAcylation contributes to the hyperglycemic exacerbation of myocardial ischemia/reperfusion injury. 28038474 5 1 dep glucose 837:843 arg1 30mmol/L 850:857 30mmol/L 850:857 30mmol/L 850:857 High glucose (HG, 30mmol/L) markedly increased ALDH2 O-GlcNAc modification compared with Con group (5mmol/L) (P<0.05). 28038474 5 1 dep glucose 837:843 arg1 HG 846:847 HG 846:847 HG 846:847 High glucose (HG, 30mmol/L) markedly increased ALDH2 O-GlcNAc modification compared with Con group (5mmol/L) (P<0.05). 28038474 9 2 theme O-GlcNAc 1460:1467 arg1 modification 1469:1480 ALDH2 O-GlcNAc modification 1454:1480 ALDH2 O-GlcNAc modification 1454:1480 Alda-1, a specific activator of ALDH2, significantly decreased ALDH2 O-GlcNAc modification and improved infarct size, apoptosis index and cardiac dysfunction induced by I/R combined with hyperglycemia. 28038474 10 3 theme therapeutic 1747:1757 arg1 potential 1759:1767 therapeutic potential 1747:1767 therapeutic potential for inducing cardioprotection 1747:1797 These findings demonstrate that ALDH2 O-GlcNAc modification is a key mechanism for the hyperglycemic exacerbation of myocardial I/R injury and Alda-1 has therapeutic potential for inducing cardioprotection. 28038474 6 4 from % 1054:1054 arg1 group 1067:1071 Con+DON group 1059:1071 Con+DON group 1059:1071 ALDH2 O-GlcNAc modification was increased by 62.9% in Con+PUGNAc group whereas it was decreased by 44.1% in Con+DON group compared with Con group (P<0.05). 28038474 5 5 theme Con 921:923 arg1 5mmol/L 932:938 5mmol/L 932:938 5mmol/L 932:938 High glucose (HG, 30mmol/L) markedly increased ALDH2 O-GlcNAc modification compared with Con group (5mmol/L) (P<0.05). 28038474 5 5 theme Con 921:923 arg1 P<0.05 942:947 P<0.05 942:947 P<0.05 942:947 High glucose (HG, 30mmol/L) markedly increased ALDH2 O-GlcNAc modification compared with Con group (5mmol/L) (P<0.05). 28038474 5 5 theme Con 921:923 arg1 group 925:929 Con group 921:929 Con group (5mmol/L) (P<0.05) 921:948 High glucose (HG, 30mmol/L) markedly increased ALDH2 O-GlcNAc modification compared with Con group (5mmol/L) (P<0.05). 28038474 9 6 theme specific 1401:1408 arg1 Alda-1 1391:1396 Alda-1 1391:1396 Alda-1 1391:1396 Alda-1, a specific activator of ALDH2, significantly decreased ALDH2 O-GlcNAc modification and improved infarct size, apoptosis index and cardiac dysfunction induced by I/R combined with hyperglycemia. 28038474 9 6 theme specific 1401:1408 arg1 activator 1410:1418 a specific activator 1399:1418 a specific activator of ALDH2 1399:1427 Alda-1, a specific activator of ALDH2, significantly decreased ALDH2 O-GlcNAc modification and improved infarct size, apoptosis index and cardiac dysfunction induced by I/R combined with hyperglycemia. 28038474 0 7 theme injury 120:125 arg1 exacerbation 72:83 the hyperglycemic exacerbation 54:83 the hyperglycemic exacerbation of myocardial ischemia/reperfusion injury 54:125 Inhibition of ALDH2 by O-GlcNAcylation contributes to the hyperglycemic exacerbation of myocardial ischemia/reperfusion injury. 28038474 9 8 theme ALDH2 1454:1458 arg1 modification 1469:1480 ALDH2 O-GlcNAc modification 1454:1480 ALDH2 O-GlcNAc modification 1454:1480 Alda-1, a specific activator of ALDH2, significantly decreased ALDH2 O-GlcNAc modification and improved infarct size, apoptosis index and cardiac dysfunction induced by I/R combined with hyperglycemia. 28038474 8 9 theme HG+H/R 1368:1373 arg1 P<0.05 1382:1387 P<0.05 1382:1387 P<0.05 1382:1387 Moreover, DON decreased levels of 4-hydroxy-2-nonenal (4-HNE), aldehydes, protein carbonyl accumulation and apoptosis index compared with HG+H/R group (P<0.05). 28038474 8 9 theme HG+H/R 1368:1373 arg1 group 1375:1379 HG+H/R group 1368:1379 HG+H/R group (P<0.05) 1368:1388 Moreover, DON decreased levels of 4-hydroxy-2-nonenal (4-HNE), aldehydes, protein carbonyl accumulation and apoptosis index compared with HG+H/R group (P<0.05). 28038474 2 10 theme O-linked-N-acetylglucosamine 323:350 arg1 mechanism 461:469 a mechanism 459:469 a mechanism for the hyperglycemic exacerbation of myocardial I/R injury 459:529 Here, we investigated whether excessive O-linked-N-acetylglucosamine (O-GlcNAc) modification of acetaldehyde dehydrogenase 2 (ALDH2), an important cardioprotective enzyme, was a mechanism for the hyperglycemic exacerbation of myocardial I/R injury. 28038474 2 10 theme O-linked-N-acetylglucosamine 323:350 arg1 modification 363:374 excessive O-linked-N-acetylglucosamine (O-GlcNAc) modification 313:374 excessive O-linked-N-acetylglucosamine (O-GlcNAc) modification of acetaldehyde dehydrogenase 2 (ALDH2), an important cardioprotective enzyme, 313:453 Here, we investigated whether excessive O-linked-N-acetylglucosamine (O-GlcNAc) modification of acetaldehyde dehydrogenase 2 (ALDH2), an important cardioprotective enzyme, was a mechanism for the hyperglycemic exacerbation of myocardial I/R injury. 28038474 8 11 theme carbonyl 1312:1319 arg1 accumulation 1321:1332 protein carbonyl accumulation 1304:1332 protein carbonyl accumulation 1304:1332 Moreover, DON decreased levels of 4-hydroxy-2-nonenal (4-HNE), aldehydes, protein carbonyl accumulation and apoptosis index compared with HG+H/R group (P<0.05). 28038474 0 12 theme ischemia/reperfusion 99:118 arg1 injury 120:125 myocardial ischemia/reperfusion injury 88:125 myocardial ischemia/reperfusion injury 88:125 Inhibition of ALDH2 by O-GlcNAcylation contributes to the hyperglycemic exacerbation of myocardial ischemia/reperfusion injury. 28038474 10 13 theme I/R 1721:1723 arg1 injury 1725:1730 myocardial I/R injury 1710:1730 myocardial I/R injury 1710:1730 These findings demonstrate that ALDH2 O-GlcNAc modification is a key mechanism for the hyperglycemic exacerbation of myocardial I/R injury and Alda-1 has therapeutic potential for inducing cardioprotection. 28038474 2 14 theme excessive 313:321 arg1 mechanism 461:469 a mechanism 459:469 a mechanism for the hyperglycemic exacerbation of myocardial I/R injury 459:529 Here, we investigated whether excessive O-linked-N-acetylglucosamine (O-GlcNAc) modification of acetaldehyde dehydrogenase 2 (ALDH2), an important cardioprotective enzyme, was a mechanism for the hyperglycemic exacerbation of myocardial I/R injury. 28038474 2 14 theme excessive 313:321 arg1 modification 363:374 excessive O-linked-N-acetylglucosamine (O-GlcNAc) modification 313:374 excessive O-linked-N-acetylglucosamine (O-GlcNAc) modification of acetaldehyde dehydrogenase 2 (ALDH2), an important cardioprotective enzyme, 313:453 Here, we investigated whether excessive O-linked-N-acetylglucosamine (O-GlcNAc) modification of acetaldehyde dehydrogenase 2 (ALDH2), an important cardioprotective enzyme, was a mechanism for the hyperglycemic exacerbation of myocardial I/R injury. 28038474 7 15 theme Con+DON 1215:1221 arg1 group 1223:1227 Con+DON group 1215:1227 Con+DON group 1215:1227 Accordingly, ALDH2 activity was decreased by 18.1% in Con+PUGNAc group whereas it was increased by 17.9% in Con+DON group. 28038474 10 16 contain has 1743:1745 arg1 Alda-1 1736:1741 Alda-1 1736:1741 Alda-1 1736:1741 These findings demonstrate that ALDH2 O-GlcNAc modification is a key mechanism for the hyperglycemic exacerbation of myocardial I/R injury and Alda-1 has therapeutic potential for inducing cardioprotection. 28038474 10 16 contain has 1743:1745 arg2 potential 1759:1767 therapeutic potential 1747:1767 therapeutic potential for inducing cardioprotection 1747:1797 These findings demonstrate that ALDH2 O-GlcNAc modification is a key mechanism for the hyperglycemic exacerbation of myocardial I/R injury and Alda-1 has therapeutic potential for inducing cardioprotection. 28038474 4 17 theme ALDH2 727:731 arg1 modification 742:753 ALDH2 O-GlcNAc modification 727:753 ALDH2 O-GlcNAc modification 727:753 ALDH2 O-GlcNAc modification was increased whereas its activity was decreased in AHG+I/R and DM+I/R rats. 28038474 6 18 theme Con+DON 1059:1065 arg1 group 1067:1071 Con+DON group 1059:1071 Con+DON group 1059:1071 ALDH2 O-GlcNAc modification was increased by 62.9% in Con+PUGNAc group whereas it was decreased by 44.1% in Con+DON group compared with Con group (P<0.05). 28038474 9 19 theme infarct 1495:1501 arg1 size 1503:1506 infarct size 1495:1506 infarct size 1495:1506 Alda-1, a specific activator of ALDH2, significantly decreased ALDH2 O-GlcNAc modification and improved infarct size, apoptosis index and cardiac dysfunction induced by I/R combined with hyperglycemia. 28038474 5 20 theme ALDH2 879:883 arg1 modification 894:905 ALDH2 O-GlcNAc modification 879:905 ALDH2 O-GlcNAc modification 879:905 High glucose (HG, 30mmol/L) markedly increased ALDH2 O-GlcNAc modification compared with Con group (5mmol/L) (P<0.05). 28038474 1 21 theme myocardial 197:206 arg1 I/R 230:232 I/R 230:232 I/R 230:232 Although hyperglycemia is causally related to adverse outcomes after myocardial ischemia/reperfusion (I/R), the underlying mechanisms are largely unknown. 28038474 1 21 theme myocardial 197:206 arg1 ischemia/reperfusion 208:227 myocardial ischemia/reperfusion 197:227 myocardial ischemia/reperfusion (I/R) 197:233 Although hyperglycemia is causally related to adverse outcomes after myocardial ischemia/reperfusion (I/R), the underlying mechanisms are largely unknown. 28038474 10 22 theme ALDH2 1625:1629 arg1 mechanism 1662:1670 a key mechanism 1656:1670 a key mechanism for the hyperglycemic exacerbation of myocardial I/R injury 1656:1730 These findings demonstrate that ALDH2 O-GlcNAc modification is a key mechanism for the hyperglycemic exacerbation of myocardial I/R injury and Alda-1 has therapeutic potential for inducing cardioprotection. 28038474 10 22 theme ALDH2 1625:1629 arg1 modification 1640:1651 ALDH2 O-GlcNAc modification 1625:1651 ALDH2 O-GlcNAc modification 1625:1651 These findings demonstrate that ALDH2 O-GlcNAc modification is a key mechanism for the hyperglycemic exacerbation of myocardial I/R injury and Alda-1 has therapeutic potential for inducing cardioprotection. 28038474 5 23 theme High 832:835 arg1 glucose 837:843 High glucose 832:843 High glucose (HG, 30mmol/L) 832:858 High glucose (HG, 30mmol/L) markedly increased ALDH2 O-GlcNAc modification compared with Con group (5mmol/L) (P<0.05). 28038474 2 24 theme cardioprotective 430:445 arg1 dehydrogenase 392:404 acetaldehyde dehydrogenase 2 379:406 acetaldehyde dehydrogenase 2 (ALDH2) 379:414 Here, we investigated whether excessive O-linked-N-acetylglucosamine (O-GlcNAc) modification of acetaldehyde dehydrogenase 2 (ALDH2), an important cardioprotective enzyme, was a mechanism for the hyperglycemic exacerbation of myocardial I/R injury. 28038474 2 24 theme cardioprotective 430:445 arg1 enzyme 447:452 an important cardioprotective enzyme 417:452 an important cardioprotective enzyme 417:452 Here, we investigated whether excessive O-linked-N-acetylglucosamine (O-GlcNAc) modification of acetaldehyde dehydrogenase 2 (ALDH2), an important cardioprotective enzyme, was a mechanism for the hyperglycemic exacerbation of myocardial I/R injury. 28038474 8 25 theme protein 1304:1310 arg1 accumulation 1321:1332 protein carbonyl accumulation 1304:1332 protein carbonyl accumulation 1304:1332 Moreover, DON decreased levels of 4-hydroxy-2-nonenal (4-HNE), aldehydes, protein carbonyl accumulation and apoptosis index compared with HG+H/R group (P<0.05). 28038474 2 26 theme important 420:428 arg1 dehydrogenase 392:404 acetaldehyde dehydrogenase 2 379:406 acetaldehyde dehydrogenase 2 (ALDH2) 379:414 Here, we investigated whether excessive O-linked-N-acetylglucosamine (O-GlcNAc) modification of acetaldehyde dehydrogenase 2 (ALDH2), an important cardioprotective enzyme, was a mechanism for the hyperglycemic exacerbation of myocardial I/R injury. 28038474 2 26 theme important 420:428 arg1 enzyme 447:452 an important cardioprotective enzyme 417:452 an important cardioprotective enzyme 417:452 Here, we investigated whether excessive O-linked-N-acetylglucosamine (O-GlcNAc) modification of acetaldehyde dehydrogenase 2 (ALDH2), an important cardioprotective enzyme, was a mechanism for the hyperglycemic exacerbation of myocardial I/R injury. 28038474 2 27 theme hyperglycemic 479:491 arg1 exacerbation 493:504 the hyperglycemic exacerbation 475:504 the hyperglycemic exacerbation of myocardial I/R injury 475:529 Here, we investigated whether excessive O-linked-N-acetylglucosamine (O-GlcNAc) modification of acetaldehyde dehydrogenase 2 (ALDH2), an important cardioprotective enzyme, was a mechanism for the hyperglycemic exacerbation of myocardial I/R injury. 28038474 9 28 theme apoptosis 1509:1517 arg1 index 1519:1523 apoptosis index 1509:1523 apoptosis index 1509:1523 Alda-1, a specific activator of ALDH2, significantly decreased ALDH2 O-GlcNAc modification and improved infarct size, apoptosis index and cardiac dysfunction induced by I/R combined with hyperglycemia. 28038474 4 29 dep AHG+I/R 807:813 arg1 rats 826:829 rats 826:829 rats 826:829 ALDH2 O-GlcNAc modification was increased whereas its activity was decreased in AHG+I/R and DM+I/R rats. 28038474 2 30 mod modification 363:374 arg1 dehydrogenase 392:404 acetaldehyde dehydrogenase 2 379:406 acetaldehyde dehydrogenase 2 (ALDH2) 379:414 Here, we investigated whether excessive O-linked-N-acetylglucosamine (O-GlcNAc) modification of acetaldehyde dehydrogenase 2 (ALDH2), an important cardioprotective enzyme, was a mechanism for the hyperglycemic exacerbation of myocardial I/R injury. 28038474 2 30 mod modification 363:374 arg1 ALDH2 409:413 ALDH2 409:413 ALDH2 409:413 Here, we investigated whether excessive O-linked-N-acetylglucosamine (O-GlcNAc) modification of acetaldehyde dehydrogenase 2 (ALDH2), an important cardioprotective enzyme, was a mechanism for the hyperglycemic exacerbation of myocardial I/R injury. 28038474 2 30 mod modification 363:374 arg1 enzyme 447:452 an important cardioprotective enzyme 417:452 an important cardioprotective enzyme 417:452 Here, we investigated whether excessive O-linked-N-acetylglucosamine (O-GlcNAc) modification of acetaldehyde dehydrogenase 2 (ALDH2), an important cardioprotective enzyme, was a mechanism for the hyperglycemic exacerbation of myocardial I/R injury. 28038474 2 30 mod modification 363:374 arg3 O-linked-N-acetylglucosamine 323:350 excessive O-linked-N-acetylglucosamine (O-GlcNAc) modification 313:374 excessive O-linked-N-acetylglucosamine (O-GlcNAc) modification of acetaldehyde dehydrogenase 2 (ALDH2), an important cardioprotective enzyme, 313:453 Here, we investigated whether excessive O-linked-N-acetylglucosamine (O-GlcNAc) modification of acetaldehyde dehydrogenase 2 (ALDH2), an important cardioprotective enzyme, was a mechanism for the hyperglycemic exacerbation of myocardial I/R injury. 28038474 2 30 mod modification 363:374 arg3 O-GlcNAc 353:360 excessive O-linked-N-acetylglucosamine (O-GlcNAc) modification 313:374 excessive O-linked-N-acetylglucosamine (O-GlcNAc) modification of acetaldehyde dehydrogenase 2 (ALDH2), an important cardioprotective enzyme, 313:453 Here, we investigated whether excessive O-linked-N-acetylglucosamine (O-GlcNAc) modification of acetaldehyde dehydrogenase 2 (ALDH2), an important cardioprotective enzyme, was a mechanism for the hyperglycemic exacerbation of myocardial I/R injury. 28038474 2 31 theme O-GlcNAc 353:360 arg1 mechanism 461:469 a mechanism 459:469 a mechanism for the hyperglycemic exacerbation of myocardial I/R injury 459:529 Here, we investigated whether excessive O-linked-N-acetylglucosamine (O-GlcNAc) modification of acetaldehyde dehydrogenase 2 (ALDH2), an important cardioprotective enzyme, was a mechanism for the hyperglycemic exacerbation of myocardial I/R injury. 28038474 2 31 theme O-GlcNAc 353:360 arg1 modification 363:374 excessive O-linked-N-acetylglucosamine (O-GlcNAc) modification 313:374 excessive O-linked-N-acetylglucosamine (O-GlcNAc) modification of acetaldehyde dehydrogenase 2 (ALDH2), an important cardioprotective enzyme, 313:453 Here, we investigated whether excessive O-linked-N-acetylglucosamine (O-GlcNAc) modification of acetaldehyde dehydrogenase 2 (ALDH2), an important cardioprotective enzyme, was a mechanism for the hyperglycemic exacerbation of myocardial I/R injury. 28038474 9 32 theme cardiac 1529:1535 arg1 dysfunction 1537:1547 cardiac dysfunction 1529:1547 cardiac dysfunction 1529:1547 Alda-1, a specific activator of ALDH2, significantly decreased ALDH2 O-GlcNAc modification and improved infarct size, apoptosis index and cardiac dysfunction induced by I/R combined with hyperglycemia. 28038474 0 33 theme ALDH2 14:18 arg1 Inhibition 0:9 Inhibition 0:9 Inhibition of ALDH2 by O-GlcNAcylation 0:37 Inhibition of ALDH2 by O-GlcNAcylation contributes to the hyperglycemic exacerbation of myocardial ischemia/reperfusion injury. 28038474 6 34 theme O-GlcNAc 957:964 arg1 modification 966:977 ALDH2 O-GlcNAc modification 951:977 ALDH2 O-GlcNAc modification 951:977 ALDH2 O-GlcNAc modification was increased by 62.9% in Con+PUGNAc group whereas it was decreased by 44.1% in Con+DON group compared with Con group (P<0.05). 28038474 10 35 theme myocardial 1710:1719 arg1 injury 1725:1730 myocardial I/R injury 1710:1730 myocardial I/R injury 1710:1730 These findings demonstrate that ALDH2 O-GlcNAc modification is a key mechanism for the hyperglycemic exacerbation of myocardial I/R injury and Alda-1 has therapeutic potential for inducing cardioprotection. 28038474 3 36 theme normal 689:694 arg1 NS 704:705 NS 704:705 NS 704:705 Both acute hyperglycemia (AHG) and diabetes (DM)-induced chronic hyperglycemia increased cardiac dysfunction, infarct size and apoptosis index compared with normal saline (NS)+I/R rats (P<0.05). 28038474 3 36 theme normal 689:694 arg1 saline 696:701 normal saline 689:701 normal saline (NS)+I/R rats (P<0.05) 689:724 Both acute hyperglycemia (AHG) and diabetes (DM)-induced chronic hyperglycemia increased cardiac dysfunction, infarct size and apoptosis index compared with normal saline (NS)+I/R rats (P<0.05). 28038474 3 37 theme chronic 589:595 arg1 hyperglycemia 597:609 diabetes (DM)-induced chronic hyperglycemia 567:609 diabetes (DM)-induced chronic hyperglycemia 567:609 Both acute hyperglycemia (AHG) and diabetes (DM)-induced chronic hyperglycemia increased cardiac dysfunction, infarct size and apoptosis index compared with normal saline (NS)+I/R rats (P<0.05). 28038474 10 38 theme O-GlcNAc 1631:1638 arg1 mechanism 1662:1670 a key mechanism 1656:1670 a key mechanism for the hyperglycemic exacerbation of myocardial I/R injury 1656:1730 These findings demonstrate that ALDH2 O-GlcNAc modification is a key mechanism for the hyperglycemic exacerbation of myocardial I/R injury and Alda-1 has therapeutic potential for inducing cardioprotection. 28038474 10 38 theme O-GlcNAc 1631:1638 arg1 modification 1640:1651 ALDH2 O-GlcNAc modification 1625:1651 ALDH2 O-GlcNAc modification 1625:1651 These findings demonstrate that ALDH2 O-GlcNAc modification is a key mechanism for the hyperglycemic exacerbation of myocardial I/R injury and Alda-1 has therapeutic potential for inducing cardioprotection. 28038474 2 39 theme injury 524:529 arg1 exacerbation 493:504 the hyperglycemic exacerbation 475:504 the hyperglycemic exacerbation of myocardial I/R injury 475:529 Here, we investigated whether excessive O-linked-N-acetylglucosamine (O-GlcNAc) modification of acetaldehyde dehydrogenase 2 (ALDH2), an important cardioprotective enzyme, was a mechanism for the hyperglycemic exacerbation of myocardial I/R injury. 28038474 6 40 theme ALDH2 951:955 arg1 modification 966:977 ALDH2 O-GlcNAc modification 951:977 ALDH2 O-GlcNAc modification 951:977 ALDH2 O-GlcNAc modification was increased by 62.9% in Con+PUGNAc group whereas it was decreased by 44.1% in Con+DON group compared with Con group (P<0.05). 28038474 9 41 theme ALDH2 1423:1427 arg1 Alda-1 1391:1396 Alda-1 1391:1396 Alda-1 1391:1396 Alda-1, a specific activator of ALDH2, significantly decreased ALDH2 O-GlcNAc modification and improved infarct size, apoptosis index and cardiac dysfunction induced by I/R combined with hyperglycemia. 28038474 9 41 theme ALDH2 1423:1427 arg1 activator 1410:1418 a specific activator 1399:1418 a specific activator of ALDH2 1399:1427 Alda-1, a specific activator of ALDH2, significantly decreased ALDH2 O-GlcNAc modification and improved infarct size, apoptosis index and cardiac dysfunction induced by I/R combined with hyperglycemia. 28038474 3 42 theme saline 696:701 arg1 P<0.05 718:723 P<0.05 718:723 P<0.05 718:723 Both acute hyperglycemia (AHG) and diabetes (DM)-induced chronic hyperglycemia increased cardiac dysfunction, infarct size and apoptosis index compared with normal saline (NS)+I/R rats (P<0.05). 28038474 3 42 theme saline 696:701 arg1 rats 712:715 normal saline (NS)+I/R rats 689:715 normal saline (NS)+I/R rats (P<0.05) 689:724 Both acute hyperglycemia (AHG) and diabetes (DM)-induced chronic hyperglycemia increased cardiac dysfunction, infarct size and apoptosis index compared with normal saline (NS)+I/R rats (P<0.05). 28038474 8 43 theme apoptosis 1338:1346 arg1 index 1348:1352 apoptosis index 1338:1352 apoptosis index 1338:1352 Moreover, DON decreased levels of 4-hydroxy-2-nonenal (4-HNE), aldehydes, protein carbonyl accumulation and apoptosis index compared with HG+H/R group (P<0.05). 28038474 5 44 theme O-GlcNAc 885:892 arg1 modification 894:905 ALDH2 O-GlcNAc modification 879:905 ALDH2 O-GlcNAc modification 879:905 High glucose (HG, 30mmol/L) markedly increased ALDH2 O-GlcNAc modification compared with Con group (5mmol/L) (P<0.05). 28038474 7 45 from % 1210:1210 arg1 group 1223:1227 Con+DON group 1215:1227 Con+DON group 1215:1227 Accordingly, ALDH2 activity was decreased by 18.1% in Con+PUGNAc group whereas it was increased by 17.9% in Con+DON group. 28038474 2 46 theme I/R 520:522 arg1 injury 524:529 myocardial I/R injury 509:529 myocardial I/R injury 509:529 Here, we investigated whether excessive O-linked-N-acetylglucosamine (O-GlcNAc) modification of acetaldehyde dehydrogenase 2 (ALDH2), an important cardioprotective enzyme, was a mechanism for the hyperglycemic exacerbation of myocardial I/R injury. 28038474 7 47 theme ALDH2 1120:1124 arg1 activity 1126:1133 ALDH2 activity 1120:1133 ALDH2 activity 1120:1133 Accordingly, ALDH2 activity was decreased by 18.1% in Con+PUGNAc group whereas it was increased by 17.9% in Con+DON group. 28038474 3 48 theme infarct 642:648 arg1 size 650:653 infarct size 642:653 infarct size 642:653 Both acute hyperglycemia (AHG) and diabetes (DM)-induced chronic hyperglycemia increased cardiac dysfunction, infarct size and apoptosis index compared with normal saline (NS)+I/R rats (P<0.05). 28038474 1 49 theme underlying 240:249 arg1 mechanisms 251:260 the underlying mechanisms 236:260 the underlying mechanisms 236:260 Although hyperglycemia is causally related to adverse outcomes after myocardial ischemia/reperfusion (I/R), the underlying mechanisms are largely unknown. 28038474 1 49 theme underlying 240:249 arg1 unknown 274:280 unknown 274:280 unknown 274:280 Although hyperglycemia is causally related to adverse outcomes after myocardial ischemia/reperfusion (I/R), the underlying mechanisms are largely unknown. 28038474 2 50 theme myocardial 509:518 arg1 injury 524:529 myocardial I/R injury 509:529 myocardial I/R injury 509:529 Here, we investigated whether excessive O-linked-N-acetylglucosamine (O-GlcNAc) modification of acetaldehyde dehydrogenase 2 (ALDH2), an important cardioprotective enzyme, was a mechanism for the hyperglycemic exacerbation of myocardial I/R injury. 28038474 3 51 theme cardiac 621:627 arg1 dysfunction 629:639 cardiac dysfunction 621:639 cardiac dysfunction 621:639 Both acute hyperglycemia (AHG) and diabetes (DM)-induced chronic hyperglycemia increased cardiac dysfunction, infarct size and apoptosis index compared with normal saline (NS)+I/R rats (P<0.05). 28038474 3 52 theme acute 537:541 arg1 AHG 558:560 AHG 558:560 AHG 558:560 Both acute hyperglycemia (AHG) and diabetes (DM)-induced chronic hyperglycemia increased cardiac dysfunction, infarct size and apoptosis index compared with normal saline (NS)+I/R rats (P<0.05). 28038474 3 52 theme acute 537:541 arg1 hyperglycemia 543:555 acute hyperglycemia 537:555 acute hyperglycemia (AHG) 537:561 Both acute hyperglycemia (AHG) and diabetes (DM)-induced chronic hyperglycemia increased cardiac dysfunction, infarct size and apoptosis index compared with normal saline (NS)+I/R rats (P<0.05). 28038474 10 53 theme hyperglycemic 1680:1692 arg1 exacerbation 1694:1705 the hyperglycemic exacerbation 1676:1705 the hyperglycemic exacerbation of myocardial I/R injury 1676:1730 These findings demonstrate that ALDH2 O-GlcNAc modification is a key mechanism for the hyperglycemic exacerbation of myocardial I/R injury and Alda-1 has therapeutic potential for inducing cardioprotection. 28038474 8 54 theme 4-hydroxy-2-nonenal 1264:1282 arg1 index 1348:1352 apoptosis index 1338:1352 apoptosis index 1338:1352 Moreover, DON decreased levels of 4-hydroxy-2-nonenal (4-HNE), aldehydes, protein carbonyl accumulation and apoptosis index compared with HG+H/R group (P<0.05). 28038474 8 54 theme 4-hydroxy-2-nonenal 1264:1282 arg1 aldehydes 1293:1301 aldehydes 1293:1301 aldehydes 1293:1301 Moreover, DON decreased levels of 4-hydroxy-2-nonenal (4-HNE), aldehydes, protein carbonyl accumulation and apoptosis index compared with HG+H/R group (P<0.05). 28038474 8 54 theme 4-hydroxy-2-nonenal 1264:1282 arg1 levels 1254:1259 levels 1254:1259 levels of 4-hydroxy-2-nonenal (4-HNE) 1254:1290 Moreover, DON decreased levels of 4-hydroxy-2-nonenal (4-HNE), aldehydes, protein carbonyl accumulation and apoptosis index compared with HG+H/R group (P<0.05). 28038474 8 54 theme 4-hydroxy-2-nonenal 1264:1282 arg1 accumulation 1321:1332 protein carbonyl accumulation 1304:1332 protein carbonyl accumulation 1304:1332 Moreover, DON decreased levels of 4-hydroxy-2-nonenal (4-HNE), aldehydes, protein carbonyl accumulation and apoptosis index compared with HG+H/R group (P<0.05). 28038474 2 55 theme dehydrogenase 392:404 arg1 mechanism 461:469 a mechanism 459:469 a mechanism for the hyperglycemic exacerbation of myocardial I/R injury 459:529 Here, we investigated whether excessive O-linked-N-acetylglucosamine (O-GlcNAc) modification of acetaldehyde dehydrogenase 2 (ALDH2), an important cardioprotective enzyme, was a mechanism for the hyperglycemic exacerbation of myocardial I/R injury. 28038474 2 55 theme dehydrogenase 392:404 arg1 modification 363:374 excessive O-linked-N-acetylglucosamine (O-GlcNAc) modification 313:374 excessive O-linked-N-acetylglucosamine (O-GlcNAc) modification of acetaldehyde dehydrogenase 2 (ALDH2), an important cardioprotective enzyme, 313:453 Here, we investigated whether excessive O-linked-N-acetylglucosamine (O-GlcNAc) modification of acetaldehyde dehydrogenase 2 (ALDH2), an important cardioprotective enzyme, was a mechanism for the hyperglycemic exacerbation of myocardial I/R injury. 28038474 3 56 theme +I/R 707:710 arg1 P<0.05 718:723 P<0.05 718:723 P<0.05 718:723 Both acute hyperglycemia (AHG) and diabetes (DM)-induced chronic hyperglycemia increased cardiac dysfunction, infarct size and apoptosis index compared with normal saline (NS)+I/R rats (P<0.05). 28038474 3 56 theme +I/R 707:710 arg1 rats 712:715 normal saline (NS)+I/R rats 689:715 normal saline (NS)+I/R rats (P<0.05) 689:724 Both acute hyperglycemia (AHG) and diabetes (DM)-induced chronic hyperglycemia increased cardiac dysfunction, infarct size and apoptosis index compared with normal saline (NS)+I/R rats (P<0.05). 28038474 3 57 theme apoptosis 659:667 arg1 index 669:673 apoptosis index 659:673 apoptosis index 659:673 Both acute hyperglycemia (AHG) and diabetes (DM)-induced chronic hyperglycemia increased cardiac dysfunction, infarct size and apoptosis index compared with normal saline (NS)+I/R rats (P<0.05). 28038474 2 58 theme acetaldehyde 379:390 arg1 dehydrogenase 392:404 acetaldehyde dehydrogenase 2 379:406 acetaldehyde dehydrogenase 2 (ALDH2) 379:414 Here, we investigated whether excessive O-linked-N-acetylglucosamine (O-GlcNAc) modification of acetaldehyde dehydrogenase 2 (ALDH2), an important cardioprotective enzyme, was a mechanism for the hyperglycemic exacerbation of myocardial I/R injury. 28038474 2 58 theme acetaldehyde 379:390 arg1 ALDH2 409:413 ALDH2 409:413 ALDH2 409:413 Here, we investigated whether excessive O-linked-N-acetylglucosamine (O-GlcNAc) modification of acetaldehyde dehydrogenase 2 (ALDH2), an important cardioprotective enzyme, was a mechanism for the hyperglycemic exacerbation of myocardial I/R injury. 28038474 2 58 theme acetaldehyde 379:390 arg1 enzyme 447:452 an important cardioprotective enzyme 417:452 an important cardioprotective enzyme 417:452 Here, we investigated whether excessive O-linked-N-acetylglucosamine (O-GlcNAc) modification of acetaldehyde dehydrogenase 2 (ALDH2), an important cardioprotective enzyme, was a mechanism for the hyperglycemic exacerbation of myocardial I/R injury. 28038474 3 59 theme -induced 580:587 arg1 hyperglycemia 597:609 diabetes (DM)-induced chronic hyperglycemia 567:609 diabetes (DM)-induced chronic hyperglycemia 567:609 Both acute hyperglycemia (AHG) and diabetes (DM)-induced chronic hyperglycemia increased cardiac dysfunction, infarct size and apoptosis index compared with normal saline (NS)+I/R rats (P<0.05). 28038474 10 60 theme injury 1725:1730 arg1 exacerbation 1694:1705 the hyperglycemic exacerbation 1676:1705 the hyperglycemic exacerbation of myocardial I/R injury 1676:1730 These findings demonstrate that ALDH2 O-GlcNAc modification is a key mechanism for the hyperglycemic exacerbation of myocardial I/R injury and Alda-1 has therapeutic potential for inducing cardioprotection. 28038474 4 61 theme O-GlcNAc 733:740 arg1 modification 742:753 ALDH2 O-GlcNAc modification 727:753 ALDH2 O-GlcNAc modification 727:753 ALDH2 O-GlcNAc modification was increased whereas its activity was decreased in AHG+I/R and DM+I/R rats. 28038474 10 62 theme key 1658:1660 arg1 mechanism 1662:1670 a key mechanism 1656:1670 a key mechanism for the hyperglycemic exacerbation of myocardial I/R injury 1656:1730 These findings demonstrate that ALDH2 O-GlcNAc modification is a key mechanism for the hyperglycemic exacerbation of myocardial I/R injury and Alda-1 has therapeutic potential for inducing cardioprotection. 28038474 10 62 theme key 1658:1660 arg1 modification 1640:1651 ALDH2 O-GlcNAc modification 1625:1651 ALDH2 O-GlcNAc modification 1625:1651 These findings demonstrate that ALDH2 O-GlcNAc modification is a key mechanism for the hyperglycemic exacerbation of myocardial I/R injury and Alda-1 has therapeutic potential for inducing cardioprotection. 28038474 6 63 theme Con 1087:1089 arg1 P<0.05 1098:1103 P<0.05 1098:1103 P<0.05 1098:1103 ALDH2 O-GlcNAc modification was increased by 62.9% in Con+PUGNAc group whereas it was decreased by 44.1% in Con+DON group compared with Con group (P<0.05). 28038474 6 63 theme Con 1087:1089 arg1 group 1091:1095 Con group 1087:1095 Con group (P<0.05) 1087:1104 ALDH2 O-GlcNAc modification was increased by 62.9% in Con+PUGNAc group whereas it was decreased by 44.1% in Con+DON group compared with Con group (P<0.05). 28038474 6 64 theme Con+PUGNAc 1005:1014 arg1 group 1016:1020 Con+PUGNAc group 1005:1020 Con+PUGNAc group 1005:1020 ALDH2 O-GlcNAc modification was increased by 62.9% in Con+PUGNAc group whereas it was decreased by 44.1% in Con+DON group compared with Con group (P<0.05). 28038474 0 65 theme hyperglycemic 58:70 arg1 exacerbation 72:83 the hyperglycemic exacerbation 54:83 the hyperglycemic exacerbation of myocardial ischemia/reperfusion injury 54:125 Inhibition of ALDH2 by O-GlcNAcylation contributes to the hyperglycemic exacerbation of myocardial ischemia/reperfusion injury. 28038474 1 66 theme adverse 174:180 arg1 outcomes 182:189 adverse outcomes 174:189 adverse outcomes after myocardial ischemia/reperfusion (I/R) 174:233 Although hyperglycemia is causally related to adverse outcomes after myocardial ischemia/reperfusion (I/R), the underlying mechanisms are largely unknown. 28038474 7 67 theme Con+PUGNAc 1161:1170 arg1 group 1172:1176 Con+PUGNAc group 1161:1176 Con+PUGNAc group 1161:1176 Accordingly, ALDH2 activity was decreased by 18.1% in Con+PUGNAc group whereas it was increased by 17.9% in Con+DON group. 26337219 3 0 theme phosphate 974:982 arg1 reabsorption 949:960 reabsorption 949:960 reabsorption of filtered phosphate in the kidneys 949:997 The medical and dental pathology is believed to be caused primarily by high serum phosphate levels (hyperphosphatemia), which, in turn, is caused by failure of GALNT3 to glycosylate the phosphate regulator protein FGF23, impairing its ability inhibit reabsorption of filtered phosphate in the kidneys. 26337219 3 1 dep ability 933:939 arg1 inhibit 941:947 inhibit 941:947 inhibit reabsorption of filtered phosphate in the kidneys 941:997 The medical and dental pathology is believed to be caused primarily by high serum phosphate levels (hyperphosphatemia), which, in turn, is caused by failure of GALNT3 to glycosylate the phosphate regulator protein FGF23, impairing its ability inhibit reabsorption of filtered phosphate in the kidneys. 26337219 0 2 theme tumoral 86:92 arg1 HFTC 106:109 HFTC 106:109 HFTC 106:109 Root anomalies and dentin dysplasia in autosomal recessive hyperphosphatemic familial tumoral calcinosis (HFTC). 26337219 0 2 theme tumoral 86:92 arg1 calcinosis 94:103 autosomal recessive hyperphosphatemic familial tumoral calcinosis 39:103 autosomal recessive hyperphosphatemic familial tumoral calcinosis (HFTC) 39:110 Root anomalies and dentin dysplasia in autosomal recessive hyperphosphatemic familial tumoral calcinosis (HFTC). 26337219 0 3 from anomalies 5:13 arg1 HFTC 106:109 HFTC 106:109 HFTC 106:109 Root anomalies and dentin dysplasia in autosomal recessive hyperphosphatemic familial tumoral calcinosis (HFTC). 26337219 0 3 from anomalies 5:13 arg1 calcinosis 94:103 autosomal recessive hyperphosphatemic familial tumoral calcinosis 39:103 autosomal recessive hyperphosphatemic familial tumoral calcinosis (HFTC) 39:110 Root anomalies and dentin dysplasia in autosomal recessive hyperphosphatemic familial tumoral calcinosis (HFTC). 26337219 2 4 theme case 417:420 arg1 report 422:427 this HFTC case report 407:427 this HFTC case report 407:427 (1) In this HFTC case report, we document the dental phenotype associated with a homozygous missense mutation (g.29077 C>T; c.484 C>T; p.Arg162*) in GALNT3 (OMIM 6017563), a gene encoding UDP-GalNAc transferase 3 that catalyzes the first step of O-linked oligosaccharide biosynthesis in the Golgi. 26337219 3 5 theme filtered 965:972 arg1 phosphate 974:982 filtered phosphate 965:982 filtered phosphate 965:982 The medical and dental pathology is believed to be caused primarily by high serum phosphate levels (hyperphosphatemia), which, in turn, is caused by failure of GALNT3 to glycosylate the phosphate regulator protein FGF23, impairing its ability inhibit reabsorption of filtered phosphate in the kidneys. 26337219 1 6 theme tooth 261:265 arg1 defects 272:278 tooth root defects 261:278 tooth root defects 261:278 Hyperphosphatemic familial tumoral calcinosis (HFTC, OMIM #211900) is an autosomal recessive metabolic disorder characterized by hyperphosphatemia, tooth root defects, and the progressive deposition of calcium phosphate crystals in periarticular spaces, soft tissues, and sometimes bone. 26337219 2 7 link O-linked 646:653 arg1 biosynthesis 671:682 O-linked oligosaccharide biosynthesis 646:682 O-linked oligosaccharide biosynthesis 646:682 (1) In this HFTC case report, we document the dental phenotype associated with a homozygous missense mutation (g.29077 C>T; c.484 C>T; p.Arg162*) in GALNT3 (OMIM 6017563), a gene encoding UDP-GalNAc transferase 3 that catalyzes the first step of O-linked oligosaccharide biosynthesis in the Golgi. 26337219 1 8 from deposition 301:310 arg1 spaces 359:364 periarticular spaces 345:364 periarticular spaces 345:364 Hyperphosphatemic familial tumoral calcinosis (HFTC, OMIM #211900) is an autosomal recessive metabolic disorder characterized by hyperphosphatemia, tooth root defects, and the progressive deposition of calcium phosphate crystals in periarticular spaces, soft tissues, and sometimes bone. 26337219 1 8 from deposition 301:310 arg1 tissues 372:378 soft tissues 367:378 soft tissues 367:378 Hyperphosphatemic familial tumoral calcinosis (HFTC, OMIM #211900) is an autosomal recessive metabolic disorder characterized by hyperphosphatemia, tooth root defects, and the progressive deposition of calcium phosphate crystals in periarticular spaces, soft tissues, and sometimes bone. 26337219 1 9 theme root 267:270 arg1 defects 272:278 tooth root defects 261:278 tooth root defects 261:278 Hyperphosphatemic familial tumoral calcinosis (HFTC, OMIM #211900) is an autosomal recessive metabolic disorder characterized by hyperphosphatemia, tooth root defects, and the progressive deposition of calcium phosphate crystals in periarticular spaces, soft tissues, and sometimes bone. 26337219 2 10 theme missense 492:499 arg1 * 543:543 g.29077 C>T; c.484 C>T; p.Arg162* 511:543 g.29077 C>T; c.484 C>T; p.Arg162* 511:543 (1) In this HFTC case report, we document the dental phenotype associated with a homozygous missense mutation (g.29077 C>T; c.484 C>T; p.Arg162*) in GALNT3 (OMIM 6017563), a gene encoding UDP-GalNAc transferase 3 that catalyzes the first step of O-linked oligosaccharide biosynthesis in the Golgi. 26337219 2 10 theme missense 492:499 arg1 mutation 501:508 a homozygous missense mutation 479:508 a homozygous missense mutation (g.29077 C>T; c.484 C>T; p.Arg162*) in GALNT3 (OMIM 6017563), a gene encoding UDP-GalNAc transferase 3 that catalyzes the first step of O-linked oligosaccharide biosynthesis in the Golgi 479:695 (1) In this HFTC case report, we document the dental phenotype associated with a homozygous missense mutation (g.29077 C>T; c.484 C>T; p.Arg162*) in GALNT3 (OMIM 6017563), a gene encoding UDP-GalNAc transferase 3 that catalyzes the first step of O-linked oligosaccharide biosynthesis in the Golgi. 26337219 2 11 dep document 433:440 arg1 1 401:401 1 401:401 1 401:401 (1) In this HFTC case report, we document the dental phenotype associated with a homozygous missense mutation (g.29077 C>T; c.484 C>T; p.Arg162*) in GALNT3 (OMIM 6017563), a gene encoding UDP-GalNAc transferase 3 that catalyzes the first step of O-linked oligosaccharide biosynthesis in the Golgi. 26337219 3 12 theme protein 904:910 arg1 FGF23 912:916 the phosphate regulator protein FGF23 880:916 the phosphate regulator protein FGF23 880:916 The medical and dental pathology is believed to be caused primarily by high serum phosphate levels (hyperphosphatemia), which, in turn, is caused by failure of GALNT3 to glycosylate the phosphate regulator protein FGF23, impairing its ability inhibit reabsorption of filtered phosphate in the kidneys. 26337219 1 13 dep calcinosis 148:157 arg1 HFTC 160:163 HFTC 160:163 HFTC 160:163 Hyperphosphatemic familial tumoral calcinosis (HFTC, OMIM #211900) is an autosomal recessive metabolic disorder characterized by hyperphosphatemia, tooth root defects, and the progressive deposition of calcium phosphate crystals in periarticular spaces, soft tissues, and sometimes bone. 26337219 1 13 dep calcinosis 148:157 arg1 # 171:171 # 171:171 # 171:171 Hyperphosphatemic familial tumoral calcinosis (HFTC, OMIM #211900) is an autosomal recessive metabolic disorder characterized by hyperphosphatemia, tooth root defects, and the progressive deposition of calcium phosphate crystals in periarticular spaces, soft tissues, and sometimes bone. 26337219 2 14 theme homozygous 481:490 arg1 * 543:543 g.29077 C>T; c.484 C>T; p.Arg162* 511:543 g.29077 C>T; c.484 C>T; p.Arg162* 511:543 (1) In this HFTC case report, we document the dental phenotype associated with a homozygous missense mutation (g.29077 C>T; c.484 C>T; p.Arg162*) in GALNT3 (OMIM 6017563), a gene encoding UDP-GalNAc transferase 3 that catalyzes the first step of O-linked oligosaccharide biosynthesis in the Golgi. 26337219 2 14 theme homozygous 481:490 arg1 mutation 501:508 a homozygous missense mutation 479:508 a homozygous missense mutation (g.29077 C>T; c.484 C>T; p.Arg162*) in GALNT3 (OMIM 6017563), a gene encoding UDP-GalNAc transferase 3 that catalyzes the first step of O-linked oligosaccharide biosynthesis in the Golgi 479:695 (1) In this HFTC case report, we document the dental phenotype associated with a homozygous missense mutation (g.29077 C>T; c.484 C>T; p.Arg162*) in GALNT3 (OMIM 6017563), a gene encoding UDP-GalNAc transferase 3 that catalyzes the first step of O-linked oligosaccharide biosynthesis in the Golgi. 26337219 1 15 theme soft 367:370 arg1 tissues 372:378 soft tissues 367:378 soft tissues 367:378 Hyperphosphatemic familial tumoral calcinosis (HFTC, OMIM #211900) is an autosomal recessive metabolic disorder characterized by hyperphosphatemia, tooth root defects, and the progressive deposition of calcium phosphate crystals in periarticular spaces, soft tissues, and sometimes bone. 26337219 2 16 theme C>T 519:521 arg1 * 543:543 g.29077 C>T; c.484 C>T; p.Arg162* 511:543 g.29077 C>T; c.484 C>T; p.Arg162* 511:543 (1) In this HFTC case report, we document the dental phenotype associated with a homozygous missense mutation (g.29077 C>T; c.484 C>T; p.Arg162*) in GALNT3 (OMIM 6017563), a gene encoding UDP-GalNAc transferase 3 that catalyzes the first step of O-linked oligosaccharide biosynthesis in the Golgi. 26337219 2 16 theme C>T 519:521 arg1 mutation 501:508 a homozygous missense mutation 479:508 a homozygous missense mutation (g.29077 C>T; c.484 C>T; p.Arg162*) in GALNT3 (OMIM 6017563), a gene encoding UDP-GalNAc transferase 3 that catalyzes the first step of O-linked oligosaccharide biosynthesis in the Golgi 479:695 (1) In this HFTC case report, we document the dental phenotype associated with a homozygous missense mutation (g.29077 C>T; c.484 C>T; p.Arg162*) in GALNT3 (OMIM 6017563), a gene encoding UDP-GalNAc transferase 3 that catalyzes the first step of O-linked oligosaccharide biosynthesis in the Golgi. 26337219 2 17 theme dental 446:451 arg1 phenotype 453:461 the dental phenotype 442:461 the dental phenotype associated with a homozygous missense mutation (g.29077 C>T; c.484 C>T; p.Arg162*) in GALNT3 (OMIM 6017563), a gene encoding UDP-GalNAc transferase 3 that catalyzes the first step of O-linked oligosaccharide biosynthesis in the Golgi 442:695 (1) In this HFTC case report, we document the dental phenotype associated with a homozygous missense mutation (g.29077 C>T; c.484 C>T; p.Arg162*) in GALNT3 (OMIM 6017563), a gene encoding UDP-GalNAc transferase 3 that catalyzes the first step of O-linked oligosaccharide biosynthesis in the Golgi. 26337219 0 18 theme Root 0:3 arg1 anomalies 5:13 Root anomalies 0:13 Root anomalies 0:13 Root anomalies and dentin dysplasia in autosomal recessive hyperphosphatemic familial tumoral calcinosis (HFTC). 26337219 0 19 from dysplasia 26:34 arg1 HFTC 106:109 HFTC 106:109 HFTC 106:109 Root anomalies and dentin dysplasia in autosomal recessive hyperphosphatemic familial tumoral calcinosis (HFTC). 26337219 0 19 from dysplasia 26:34 arg1 calcinosis 94:103 autosomal recessive hyperphosphatemic familial tumoral calcinosis 39:103 autosomal recessive hyperphosphatemic familial tumoral calcinosis (HFTC) 39:110 Root anomalies and dentin dysplasia in autosomal recessive hyperphosphatemic familial tumoral calcinosis (HFTC). 26337219 3 20 gly glycosylate 868:878 arg1 FGF23 912:916 the phosphate regulator protein FGF23 880:916 the phosphate regulator protein FGF23 880:916 The medical and dental pathology is believed to be caused primarily by high serum phosphate levels (hyperphosphatemia), which, in turn, is caused by failure of GALNT3 to glycosylate the phosphate regulator protein FGF23, impairing its ability inhibit reabsorption of filtered phosphate in the kidneys. 26337219 2 21 from step 638:641 arg1 Golgi 691:695 the Golgi 687:695 the Golgi 687:695 (1) In this HFTC case report, we document the dental phenotype associated with a homozygous missense mutation (g.29077 C>T; c.484 C>T; p.Arg162*) in GALNT3 (OMIM 6017563), a gene encoding UDP-GalNAc transferase 3 that catalyzes the first step of O-linked oligosaccharide biosynthesis in the Golgi. 26337219 1 22 theme periarticular 345:357 arg1 spaces 359:364 periarticular spaces 345:364 periarticular spaces 345:364 Hyperphosphatemic familial tumoral calcinosis (HFTC, OMIM #211900) is an autosomal recessive metabolic disorder characterized by hyperphosphatemia, tooth root defects, and the progressive deposition of calcium phosphate crystals in periarticular spaces, soft tissues, and sometimes bone. 26337219 0 23 theme dentin 19:24 arg1 dysplasia 26:34 dentin dysplasia 19:34 dentin dysplasia 19:34 Root anomalies and dentin dysplasia in autosomal recessive hyperphosphatemic familial tumoral calcinosis (HFTC). 26337219 1 24 dep spaces 359:364 arg1 bone 395:398 bone 395:398 bone 395:398 Hyperphosphatemic familial tumoral calcinosis (HFTC, OMIM #211900) is an autosomal recessive metabolic disorder characterized by hyperphosphatemia, tooth root defects, and the progressive deposition of calcium phosphate crystals in periarticular spaces, soft tissues, and sometimes bone. 26337219 2 25 theme UDP-GalNAc 588:597 arg1 transferase 599:609 UDP-GalNAc transferase 3 588:611 UDP-GalNAc transferase 3 that catalyzes the first step of O-linked oligosaccharide biosynthesis in the Golgi 588:695 (1) In this HFTC case report, we document the dental phenotype associated with a homozygous missense mutation (g.29077 C>T; c.484 C>T; p.Arg162*) in GALNT3 (OMIM 6017563), a gene encoding UDP-GalNAc transferase 3 that catalyzes the first step of O-linked oligosaccharide biosynthesis in the Golgi. 26337219 3 26 theme regulator 894:902 arg1 FGF23 912:916 the phosphate regulator protein FGF23 880:916 the phosphate regulator protein FGF23 880:916 The medical and dental pathology is believed to be caused primarily by high serum phosphate levels (hyperphosphatemia), which, in turn, is caused by failure of GALNT3 to glycosylate the phosphate regulator protein FGF23, impairing its ability inhibit reabsorption of filtered phosphate in the kidneys. 26337219 1 27 from defects 272:278 arg1 spaces 359:364 periarticular spaces 345:364 periarticular spaces 345:364 Hyperphosphatemic familial tumoral calcinosis (HFTC, OMIM #211900) is an autosomal recessive metabolic disorder characterized by hyperphosphatemia, tooth root defects, and the progressive deposition of calcium phosphate crystals in periarticular spaces, soft tissues, and sometimes bone. 26337219 1 27 from defects 272:278 arg1 tissues 372:378 soft tissues 367:378 soft tissues 367:378 Hyperphosphatemic familial tumoral calcinosis (HFTC, OMIM #211900) is an autosomal recessive metabolic disorder characterized by hyperphosphatemia, tooth root defects, and the progressive deposition of calcium phosphate crystals in periarticular spaces, soft tissues, and sometimes bone. 26337219 1 28 theme autosomal 186:194 arg1 disorder 216:223 an autosomal recessive metabolic disorder 183:223 an autosomal recessive metabolic disorder characterized by hyperphosphatemia, tooth root defects, and the progressive deposition of calcium phosphate crystals in periarticular spaces, soft tissues, and sometimes bone 183:398 Hyperphosphatemic familial tumoral calcinosis (HFTC, OMIM #211900) is an autosomal recessive metabolic disorder characterized by hyperphosphatemia, tooth root defects, and the progressive deposition of calcium phosphate crystals in periarticular spaces, soft tissues, and sometimes bone. 26337219 1 28 theme autosomal 186:194 arg1 calcinosis 148:157 Hyperphosphatemic familial tumoral calcinosis 113:157 Hyperphosphatemic familial tumoral calcinosis (HFTC, OMIM #211900) 113:178 Hyperphosphatemic familial tumoral calcinosis (HFTC, OMIM #211900) is an autosomal recessive metabolic disorder characterized by hyperphosphatemia, tooth root defects, and the progressive deposition of calcium phosphate crystals in periarticular spaces, soft tissues, and sometimes bone. 26337219 1 29 theme progressive 289:299 arg1 deposition 301:310 the progressive deposition 285:310 the progressive deposition of calcium phosphate crystals in periarticular spaces, soft tissues, and sometimes bone 285:398 Hyperphosphatemic familial tumoral calcinosis (HFTC, OMIM #211900) is an autosomal recessive metabolic disorder characterized by hyperphosphatemia, tooth root defects, and the progressive deposition of calcium phosphate crystals in periarticular spaces, soft tissues, and sometimes bone. 26337219 1 30 theme recessive 196:204 arg1 disorder 216:223 an autosomal recessive metabolic disorder 183:223 an autosomal recessive metabolic disorder characterized by hyperphosphatemia, tooth root defects, and the progressive deposition of calcium phosphate crystals in periarticular spaces, soft tissues, and sometimes bone 183:398 Hyperphosphatemic familial tumoral calcinosis (HFTC, OMIM #211900) is an autosomal recessive metabolic disorder characterized by hyperphosphatemia, tooth root defects, and the progressive deposition of calcium phosphate crystals in periarticular spaces, soft tissues, and sometimes bone. 26337219 1 30 theme recessive 196:204 arg1 calcinosis 148:157 Hyperphosphatemic familial tumoral calcinosis 113:157 Hyperphosphatemic familial tumoral calcinosis (HFTC, OMIM #211900) 113:178 Hyperphosphatemic familial tumoral calcinosis (HFTC, OMIM #211900) is an autosomal recessive metabolic disorder characterized by hyperphosphatemia, tooth root defects, and the progressive deposition of calcium phosphate crystals in periarticular spaces, soft tissues, and sometimes bone. 26337219 2 31 theme HFTC 412:415 arg1 report 422:427 this HFTC case report 407:427 this HFTC case report 407:427 (1) In this HFTC case report, we document the dental phenotype associated with a homozygous missense mutation (g.29077 C>T; c.484 C>T; p.Arg162*) in GALNT3 (OMIM 6017563), a gene encoding UDP-GalNAc transferase 3 that catalyzes the first step of O-linked oligosaccharide biosynthesis in the Golgi. 26337219 3 32 theme GALNT3 858:863 arg1 failure 847:853 failure 847:853 failure of GALNT3 to glycosylate the phosphate regulator protein FGF23, impairing its ability inhibit reabsorption of filtered phosphate in the kidneys 847:997 The medical and dental pathology is believed to be caused primarily by high serum phosphate levels (hyperphosphatemia), which, in turn, is caused by failure of GALNT3 to glycosylate the phosphate regulator protein FGF23, impairing its ability inhibit reabsorption of filtered phosphate in the kidneys. 26337219 1 33 theme metabolic 206:214 arg1 disorder 216:223 an autosomal recessive metabolic disorder 183:223 an autosomal recessive metabolic disorder characterized by hyperphosphatemia, tooth root defects, and the progressive deposition of calcium phosphate crystals in periarticular spaces, soft tissues, and sometimes bone 183:398 Hyperphosphatemic familial tumoral calcinosis (HFTC, OMIM #211900) is an autosomal recessive metabolic disorder characterized by hyperphosphatemia, tooth root defects, and the progressive deposition of calcium phosphate crystals in periarticular spaces, soft tissues, and sometimes bone. 26337219 1 33 theme metabolic 206:214 arg1 calcinosis 148:157 Hyperphosphatemic familial tumoral calcinosis 113:157 Hyperphosphatemic familial tumoral calcinosis (HFTC, OMIM #211900) 113:178 Hyperphosphatemic familial tumoral calcinosis (HFTC, OMIM #211900) is an autosomal recessive metabolic disorder characterized by hyperphosphatemia, tooth root defects, and the progressive deposition of calcium phosphate crystals in periarticular spaces, soft tissues, and sometimes bone. 26337219 0 34 theme recessive 49:57 arg1 HFTC 106:109 HFTC 106:109 HFTC 106:109 Root anomalies and dentin dysplasia in autosomal recessive hyperphosphatemic familial tumoral calcinosis (HFTC). 26337219 0 34 theme recessive 49:57 arg1 calcinosis 94:103 autosomal recessive hyperphosphatemic familial tumoral calcinosis 39:103 autosomal recessive hyperphosphatemic familial tumoral calcinosis (HFTC) 39:110 Root anomalies and dentin dysplasia in autosomal recessive hyperphosphatemic familial tumoral calcinosis (HFTC). 26337219 3 35 theme dental 714:719 arg1 pathology 721:729 The medical and dental pathology 698:729 The medical and dental pathology 698:729 The medical and dental pathology is believed to be caused primarily by high serum phosphate levels (hyperphosphatemia), which, in turn, is caused by failure of GALNT3 to glycosylate the phosphate regulator protein FGF23, impairing its ability inhibit reabsorption of filtered phosphate in the kidneys. 26337219 2 36 theme first 632:636 arg1 step 638:641 the first step 628:641 the first step of O-linked oligosaccharide biosynthesis in the Golgi 628:695 (1) In this HFTC case report, we document the dental phenotype associated with a homozygous missense mutation (g.29077 C>T; c.484 C>T; p.Arg162*) in GALNT3 (OMIM 6017563), a gene encoding UDP-GalNAc transferase 3 that catalyzes the first step of O-linked oligosaccharide biosynthesis in the Golgi. 26337219 1 37 theme Hyperphosphatemic 113:129 arg1 disorder 216:223 an autosomal recessive metabolic disorder 183:223 an autosomal recessive metabolic disorder characterized by hyperphosphatemia, tooth root defects, and the progressive deposition of calcium phosphate crystals in periarticular spaces, soft tissues, and sometimes bone 183:398 Hyperphosphatemic familial tumoral calcinosis (HFTC, OMIM #211900) is an autosomal recessive metabolic disorder characterized by hyperphosphatemia, tooth root defects, and the progressive deposition of calcium phosphate crystals in periarticular spaces, soft tissues, and sometimes bone. 26337219 1 37 theme Hyperphosphatemic 113:129 arg1 calcinosis 148:157 Hyperphosphatemic familial tumoral calcinosis 113:157 Hyperphosphatemic familial tumoral calcinosis (HFTC, OMIM #211900) 113:178 Hyperphosphatemic familial tumoral calcinosis (HFTC, OMIM #211900) is an autosomal recessive metabolic disorder characterized by hyperphosphatemia, tooth root defects, and the progressive deposition of calcium phosphate crystals in periarticular spaces, soft tissues, and sometimes bone. 26337219 0 38 theme autosomal 39:47 arg1 HFTC 106:109 HFTC 106:109 HFTC 106:109 Root anomalies and dentin dysplasia in autosomal recessive hyperphosphatemic familial tumoral calcinosis (HFTC). 26337219 0 38 theme autosomal 39:47 arg1 calcinosis 94:103 autosomal recessive hyperphosphatemic familial tumoral calcinosis 39:103 autosomal recessive hyperphosphatemic familial tumoral calcinosis (HFTC) 39:110 Root anomalies and dentin dysplasia in autosomal recessive hyperphosphatemic familial tumoral calcinosis (HFTC). 26337219 1 39 theme calcium 315:321 arg1 crystals 333:340 calcium phosphate crystals 315:340 calcium phosphate crystals 315:340 Hyperphosphatemic familial tumoral calcinosis (HFTC, OMIM #211900) is an autosomal recessive metabolic disorder characterized by hyperphosphatemia, tooth root defects, and the progressive deposition of calcium phosphate crystals in periarticular spaces, soft tissues, and sometimes bone. 26337219 1 40 from hyperphosphatemia 242:258 arg1 spaces 359:364 periarticular spaces 345:364 periarticular spaces 345:364 Hyperphosphatemic familial tumoral calcinosis (HFTC, OMIM #211900) is an autosomal recessive metabolic disorder characterized by hyperphosphatemia, tooth root defects, and the progressive deposition of calcium phosphate crystals in periarticular spaces, soft tissues, and sometimes bone. 26337219 1 40 from hyperphosphatemia 242:258 arg1 tissues 372:378 soft tissues 367:378 soft tissues 367:378 Hyperphosphatemic familial tumoral calcinosis (HFTC, OMIM #211900) is an autosomal recessive metabolic disorder characterized by hyperphosphatemia, tooth root defects, and the progressive deposition of calcium phosphate crystals in periarticular spaces, soft tissues, and sometimes bone. 26337219 1 41 theme familial 131:138 arg1 disorder 216:223 an autosomal recessive metabolic disorder 183:223 an autosomal recessive metabolic disorder characterized by hyperphosphatemia, tooth root defects, and the progressive deposition of calcium phosphate crystals in periarticular spaces, soft tissues, and sometimes bone 183:398 Hyperphosphatemic familial tumoral calcinosis (HFTC, OMIM #211900) is an autosomal recessive metabolic disorder characterized by hyperphosphatemia, tooth root defects, and the progressive deposition of calcium phosphate crystals in periarticular spaces, soft tissues, and sometimes bone. 26337219 1 41 theme familial 131:138 arg1 calcinosis 148:157 Hyperphosphatemic familial tumoral calcinosis 113:157 Hyperphosphatemic familial tumoral calcinosis (HFTC, OMIM #211900) 113:178 Hyperphosphatemic familial tumoral calcinosis (HFTC, OMIM #211900) is an autosomal recessive metabolic disorder characterized by hyperphosphatemia, tooth root defects, and the progressive deposition of calcium phosphate crystals in periarticular spaces, soft tissues, and sometimes bone. 26337219 3 42 theme phosphate 780:788 arg1 hyperphosphatemia 798:814 hyperphosphatemia 798:814 hyperphosphatemia 798:814 The medical and dental pathology is believed to be caused primarily by high serum phosphate levels (hyperphosphatemia), which, in turn, is caused by failure of GALNT3 to glycosylate the phosphate regulator protein FGF23, impairing its ability inhibit reabsorption of filtered phosphate in the kidneys. 26337219 3 42 theme phosphate 780:788 arg1 levels 790:795 high serum phosphate levels 769:795 high serum phosphate levels (hyperphosphatemia) 769:815 The medical and dental pathology is believed to be caused primarily by high serum phosphate levels (hyperphosphatemia), which, in turn, is caused by failure of GALNT3 to glycosylate the phosphate regulator protein FGF23, impairing its ability inhibit reabsorption of filtered phosphate in the kidneys. 26337219 1 43 theme phosphate 323:331 arg1 crystals 333:340 calcium phosphate crystals 315:340 calcium phosphate crystals 315:340 Hyperphosphatemic familial tumoral calcinosis (HFTC, OMIM #211900) is an autosomal recessive metabolic disorder characterized by hyperphosphatemia, tooth root defects, and the progressive deposition of calcium phosphate crystals in periarticular spaces, soft tissues, and sometimes bone. 26337219 2 44 theme C>T 530:532 arg1 * 543:543 g.29077 C>T; c.484 C>T; p.Arg162* 511:543 g.29077 C>T; c.484 C>T; p.Arg162* 511:543 (1) In this HFTC case report, we document the dental phenotype associated with a homozygous missense mutation (g.29077 C>T; c.484 C>T; p.Arg162*) in GALNT3 (OMIM 6017563), a gene encoding UDP-GalNAc transferase 3 that catalyzes the first step of O-linked oligosaccharide biosynthesis in the Golgi. 26337219 2 44 theme C>T 530:532 arg1 mutation 501:508 a homozygous missense mutation 479:508 a homozygous missense mutation (g.29077 C>T; c.484 C>T; p.Arg162*) in GALNT3 (OMIM 6017563), a gene encoding UDP-GalNAc transferase 3 that catalyzes the first step of O-linked oligosaccharide biosynthesis in the Golgi 479:695 (1) In this HFTC case report, we document the dental phenotype associated with a homozygous missense mutation (g.29077 C>T; c.484 C>T; p.Arg162*) in GALNT3 (OMIM 6017563), a gene encoding UDP-GalNAc transferase 3 that catalyzes the first step of O-linked oligosaccharide biosynthesis in the Golgi. 26337219 1 45 theme tumoral 140:146 arg1 disorder 216:223 an autosomal recessive metabolic disorder 183:223 an autosomal recessive metabolic disorder characterized by hyperphosphatemia, tooth root defects, and the progressive deposition of calcium phosphate crystals in periarticular spaces, soft tissues, and sometimes bone 183:398 Hyperphosphatemic familial tumoral calcinosis (HFTC, OMIM #211900) is an autosomal recessive metabolic disorder characterized by hyperphosphatemia, tooth root defects, and the progressive deposition of calcium phosphate crystals in periarticular spaces, soft tissues, and sometimes bone. 26337219 1 45 theme tumoral 140:146 arg1 calcinosis 148:157 Hyperphosphatemic familial tumoral calcinosis 113:157 Hyperphosphatemic familial tumoral calcinosis (HFTC, OMIM #211900) 113:178 Hyperphosphatemic familial tumoral calcinosis (HFTC, OMIM #211900) is an autosomal recessive metabolic disorder characterized by hyperphosphatemia, tooth root defects, and the progressive deposition of calcium phosphate crystals in periarticular spaces, soft tissues, and sometimes bone. 26337219 3 46 theme medical 702:708 arg1 pathology 721:729 The medical and dental pathology 698:729 The medical and dental pathology 698:729 The medical and dental pathology is believed to be caused primarily by high serum phosphate levels (hyperphosphatemia), which, in turn, is caused by failure of GALNT3 to glycosylate the phosphate regulator protein FGF23, impairing its ability inhibit reabsorption of filtered phosphate in the kidneys. 26337219 2 47 from mutation 501:508 arg1 gene 574:577 a gene 572:577 a gene encoding UDP-GalNAc transferase 3 that catalyzes the first step of O-linked oligosaccharide biosynthesis in the Golgi 572:695 (1) In this HFTC case report, we document the dental phenotype associated with a homozygous missense mutation (g.29077 C>T; c.484 C>T; p.Arg162*) in GALNT3 (OMIM 6017563), a gene encoding UDP-GalNAc transferase 3 that catalyzes the first step of O-linked oligosaccharide biosynthesis in the Golgi. 26337219 2 47 from mutation 501:508 arg1 OMIM 557:560 OMIM 6017563 557:568 OMIM 6017563 557:568 (1) In this HFTC case report, we document the dental phenotype associated with a homozygous missense mutation (g.29077 C>T; c.484 C>T; p.Arg162*) in GALNT3 (OMIM 6017563), a gene encoding UDP-GalNAc transferase 3 that catalyzes the first step of O-linked oligosaccharide biosynthesis in the Golgi. 26337219 2 47 from mutation 501:508 arg1 GALNT3 549:554 GALNT3 549:554 GALNT3 (OMIM 6017563) 549:569 (1) In this HFTC case report, we document the dental phenotype associated with a homozygous missense mutation (g.29077 C>T; c.484 C>T; p.Arg162*) in GALNT3 (OMIM 6017563), a gene encoding UDP-GalNAc transferase 3 that catalyzes the first step of O-linked oligosaccharide biosynthesis in the Golgi. 26337219 2 48 theme biosynthesis 671:682 arg1 step 638:641 the first step 628:641 the first step of O-linked oligosaccharide biosynthesis in the Golgi 628:695 (1) In this HFTC case report, we document the dental phenotype associated with a homozygous missense mutation (g.29077 C>T; c.484 C>T; p.Arg162*) in GALNT3 (OMIM 6017563), a gene encoding UDP-GalNAc transferase 3 that catalyzes the first step of O-linked oligosaccharide biosynthesis in the Golgi. 26337219 3 49 from reabsorption 949:960 arg1 kidneys 991:997 the kidneys 987:997 the kidneys 987:997 The medical and dental pathology is believed to be caused primarily by high serum phosphate levels (hyperphosphatemia), which, in turn, is caused by failure of GALNT3 to glycosylate the phosphate regulator protein FGF23, impairing its ability inhibit reabsorption of filtered phosphate in the kidneys. 26337219 3 50 theme high 769:772 arg1 hyperphosphatemia 798:814 hyperphosphatemia 798:814 hyperphosphatemia 798:814 The medical and dental pathology is believed to be caused primarily by high serum phosphate levels (hyperphosphatemia), which, in turn, is caused by failure of GALNT3 to glycosylate the phosphate regulator protein FGF23, impairing its ability inhibit reabsorption of filtered phosphate in the kidneys. 26337219 3 50 theme high 769:772 arg1 levels 790:795 high serum phosphate levels 769:795 high serum phosphate levels (hyperphosphatemia) 769:815 The medical and dental pathology is believed to be caused primarily by high serum phosphate levels (hyperphosphatemia), which, in turn, is caused by failure of GALNT3 to glycosylate the phosphate regulator protein FGF23, impairing its ability inhibit reabsorption of filtered phosphate in the kidneys. 26337219 3 51 theme phosphate 884:892 arg1 FGF23 912:916 the phosphate regulator protein FGF23 880:916 the phosphate regulator protein FGF23 880:916 The medical and dental pathology is believed to be caused primarily by high serum phosphate levels (hyperphosphatemia), which, in turn, is caused by failure of GALNT3 to glycosylate the phosphate regulator protein FGF23, impairing its ability inhibit reabsorption of filtered phosphate in the kidneys. 26337219 0 52 theme familial 77:84 arg1 HFTC 106:109 HFTC 106:109 HFTC 106:109 Root anomalies and dentin dysplasia in autosomal recessive hyperphosphatemic familial tumoral calcinosis (HFTC). 26337219 0 52 theme familial 77:84 arg1 calcinosis 94:103 autosomal recessive hyperphosphatemic familial tumoral calcinosis 39:103 autosomal recessive hyperphosphatemic familial tumoral calcinosis (HFTC) 39:110 Root anomalies and dentin dysplasia in autosomal recessive hyperphosphatemic familial tumoral calcinosis (HFTC). 26337219 2 53 theme oligosaccharide 655:669 arg1 biosynthesis 671:682 O-linked oligosaccharide biosynthesis 646:682 O-linked oligosaccharide biosynthesis 646:682 (1) In this HFTC case report, we document the dental phenotype associated with a homozygous missense mutation (g.29077 C>T; c.484 C>T; p.Arg162*) in GALNT3 (OMIM 6017563), a gene encoding UDP-GalNAc transferase 3 that catalyzes the first step of O-linked oligosaccharide biosynthesis in the Golgi. 26337219 3 54 theme serum 774:778 arg1 hyperphosphatemia 798:814 hyperphosphatemia 798:814 hyperphosphatemia 798:814 The medical and dental pathology is believed to be caused primarily by high serum phosphate levels (hyperphosphatemia), which, in turn, is caused by failure of GALNT3 to glycosylate the phosphate regulator protein FGF23, impairing its ability inhibit reabsorption of filtered phosphate in the kidneys. 26337219 3 54 theme serum 774:778 arg1 levels 790:795 high serum phosphate levels 769:795 high serum phosphate levels (hyperphosphatemia) 769:815 The medical and dental pathology is believed to be caused primarily by high serum phosphate levels (hyperphosphatemia), which, in turn, is caused by failure of GALNT3 to glycosylate the phosphate regulator protein FGF23, impairing its ability inhibit reabsorption of filtered phosphate in the kidneys. 26337219 0 55 theme hyperphosphatemic 59:75 arg1 HFTC 106:109 HFTC 106:109 HFTC 106:109 Root anomalies and dentin dysplasia in autosomal recessive hyperphosphatemic familial tumoral calcinosis (HFTC). 26337219 0 55 theme hyperphosphatemic 59:75 arg1 calcinosis 94:103 autosomal recessive hyperphosphatemic familial tumoral calcinosis 39:103 autosomal recessive hyperphosphatemic familial tumoral calcinosis (HFTC) 39:110 Root anomalies and dentin dysplasia in autosomal recessive hyperphosphatemic familial tumoral calcinosis (HFTC). 26337219 1 56 theme crystals 333:340 arg1 hyperphosphatemia 242:258 hyperphosphatemia 242:258 hyperphosphatemia 242:258 Hyperphosphatemic familial tumoral calcinosis (HFTC, OMIM #211900) is an autosomal recessive metabolic disorder characterized by hyperphosphatemia, tooth root defects, and the progressive deposition of calcium phosphate crystals in periarticular spaces, soft tissues, and sometimes bone. 26337219 1 56 theme crystals 333:340 arg1 deposition 301:310 the progressive deposition 285:310 the progressive deposition of calcium phosphate crystals in periarticular spaces, soft tissues, and sometimes bone 285:398 Hyperphosphatemic familial tumoral calcinosis (HFTC, OMIM #211900) is an autosomal recessive metabolic disorder characterized by hyperphosphatemia, tooth root defects, and the progressive deposition of calcium phosphate crystals in periarticular spaces, soft tissues, and sometimes bone. 26337219 1 56 theme crystals 333:340 arg1 defects 272:278 tooth root defects 261:278 tooth root defects 261:278 Hyperphosphatemic familial tumoral calcinosis (HFTC, OMIM #211900) is an autosomal recessive metabolic disorder characterized by hyperphosphatemia, tooth root defects, and the progressive deposition of calcium phosphate crystals in periarticular spaces, soft tissues, and sometimes bone. 26337219 2 57 theme O-linked 646:653 arg1 biosynthesis 671:682 O-linked oligosaccharide biosynthesis 646:682 O-linked oligosaccharide biosynthesis 646:682 (1) In this HFTC case report, we document the dental phenotype associated with a homozygous missense mutation (g.29077 C>T; c.484 C>T; p.Arg162*) in GALNT3 (OMIM 6017563), a gene encoding UDP-GalNAc transferase 3 that catalyzes the first step of O-linked oligosaccharide biosynthesis in the Golgi. 26784927 8 0 theme palmitoyltransferase 1056:1075 arg1 levels 970:975 mRNA levels 965:975 mRNA levels of Per2, Bmal1, Cryptochrome1 (Cry1), agouti-related peptide (AgRP), carnitine palmitoyltransferase 1C (Cpt1c), and O-linked N-acetylglucosamine transferase (Ogt) 965:1138 Thus, the AMPK inhibitor Compound C was utilized, and mRNA levels of Per2, Bmal1, Cryptochrome1 (Cry1), agouti-related peptide (AgRP), carnitine palmitoyltransferase 1C (Cpt1c), and O-linked N-acetylglucosamine transferase (Ogt) were measured. 26784927 12 1 from dysregulation 1875:1887 arg1 repression 1812:1821 AMPK-independent repression 1795:1821 AMPK-independent repression of specific genes 1795:1839 Importantly, the effects of the most commonly used AMPK inhibitor Compound C should be interpreted with caution, considering its role in AMPK-independent repression of specific genes, and especially clock gene rhythm dysregulation. 26784927 4 2 theme comparable 567:576 arg1 glucose 558:564 0.5 or 5.5 mM glucose 544:564 0.5 or 5.5 mM glucose 544:564 mHypoE-37 neurons were exposed to 0.5 or 5.5 mM glucose, comparable to physiological levels in the brain. 26784927 2 3 theme clock 347:351 arg1 expression 358:367 clock gene expression 347:367 clock gene expression 347:367 It is unclear if nutrients can directly control clock gene expression. 26784927 8 4 theme AMPK 921:924 arg1 C 945:945 the AMPK inhibitor Compound C 917:945 the AMPK inhibitor Compound C 917:945 Thus, the AMPK inhibitor Compound C was utilized, and mRNA levels of Per2, Bmal1, Cryptochrome1 (Cry1), agouti-related peptide (AgRP), carnitine palmitoyltransferase 1C (Cpt1c), and O-linked N-acetylglucosamine transferase (Ogt) were measured. 26784927 4 5 theme physiological 581:593 arg1 levels 595:600 physiological levels 581:600 physiological levels in the brain 581:613 mHypoE-37 neurons were exposed to 0.5 or 5.5 mM glucose, comparable to physiological levels in the brain. 26784927 11 6 theme genes 1530:1534 arg1 expression 1510:1519 the rhythmic expression 1497:1519 the rhythmic expression of clock genes 1497:1534 The consequences of inhibition of the rhythmic expression of clock genes, and in turn downstream metabolic mediators, such as AgRP, could have detrimental effects on overall metabolic processes. 26784927 6 7 theme mRNA 776:779 arg1 levels 781:786 Per2 mRNA levels 771:786 Per2 mRNA levels 771:786 Incubation with 5.5 mM glucose significantly shortened the period and delayed the phase of Per2 mRNA levels, but had no effect on Bmal1. 26784927 3 8 theme genes 503:507 arg1 rhythms 481:487 robust circadian rhythms 464:487 robust circadian rhythms of core clock genes 464:507 We have therefore utilized the immortalized, hypothalamic cell line mHypoE-37, which exhibits robust circadian rhythms of core clock genes. 26784927 11 9 dep such 1581:1584 arg1 as 1586:1587 as 1586:1587 as 1586:1587 The consequences of inhibition of the rhythmic expression of clock genes, and in turn downstream metabolic mediators, such as AgRP, could have detrimental effects on overall metabolic processes. 26784927 12 10 theme clock 1857:1861 arg1 dysregulation 1875:1887 clock gene rhythm dysregulation 1857:1887 clock gene rhythm dysregulation 1857:1887 Importantly, the effects of the most commonly used AMPK inhibitor Compound C should be interpreted with caution, considering its role in AMPK-independent repression of specific genes, and especially clock gene rhythm dysregulation. 26784927 8 11 theme Compound 936:943 arg1 C 945:945 the AMPK inhibitor Compound C 917:945 the AMPK inhibitor Compound C 917:945 Thus, the AMPK inhibitor Compound C was utilized, and mRNA levels of Per2, Bmal1, Cryptochrome1 (Cry1), agouti-related peptide (AgRP), carnitine palmitoyltransferase 1C (Cpt1c), and O-linked N-acetylglucosamine transferase (Ogt) were measured. 26784927 10 12 theme gene 1401:1404 arg1 expression 1406:1415 gene expression 1401:1415 gene expression 1401:1415 Because AMPK was not inhibited at the same time or concentrations as the clock genes, we suggest that the effect of Compound C on gene expression occurs through an AMPK-independent mechanism. 26784927 11 13 from consequences 1467:1478 arg1 turn 1544:1547 turn 1544:1547 turn 1544:1547 The consequences of inhibition of the rhythmic expression of clock genes, and in turn downstream metabolic mediators, such as AgRP, could have detrimental effects on overall metabolic processes. 26784927 1 14 theme proper 273:278 arg1 control 290:296 proper metabolic control 273:296 proper metabolic control 273:296 Specific neurons in the hypothalamus are regulated by peripheral hormones and nutrients to maintain proper metabolic control. 26784927 11 15 from inhibition 1483:1492 arg1 turn 1544:1547 turn 1544:1547 turn 1544:1547 The consequences of inhibition of the rhythmic expression of clock genes, and in turn downstream metabolic mediators, such as AgRP, could have detrimental effects on overall metabolic processes. 26784927 8 16 theme N-acetylglucosamine 1102:1120 arg1 Ogt 1135:1137 Ogt 1135:1137 Ogt 1135:1137 Thus, the AMPK inhibitor Compound C was utilized, and mRNA levels of Per2, Bmal1, Cryptochrome1 (Cry1), agouti-related peptide (AgRP), carnitine palmitoyltransferase 1C (Cpt1c), and O-linked N-acetylglucosamine transferase (Ogt) were measured. 26784927 8 16 theme N-acetylglucosamine 1102:1120 arg1 transferase 1122:1132 O-linked N-acetylglucosamine transferase 1093:1132 O-linked N-acetylglucosamine transferase (Ogt) 1093:1138 Thus, the AMPK inhibitor Compound C was utilized, and mRNA levels of Per2, Bmal1, Cryptochrome1 (Cry1), agouti-related peptide (AgRP), carnitine palmitoyltransferase 1C (Cpt1c), and O-linked N-acetylglucosamine transferase (Ogt) were measured. 26784927 11 17 theme overall 1629:1635 arg1 processes 1647:1655 overall metabolic processes 1629:1655 overall metabolic processes 1629:1655 The consequences of inhibition of the rhythmic expression of clock genes, and in turn downstream metabolic mediators, such as AgRP, could have detrimental effects on overall metabolic processes. 26784927 8 18 used utilized 951:958 arg2 C 945:945 the AMPK inhibitor Compound C 917:945 the AMPK inhibitor Compound C 917:945 Thus, the AMPK inhibitor Compound C was utilized, and mRNA levels of Per2, Bmal1, Cryptochrome1 (Cry1), agouti-related peptide (AgRP), carnitine palmitoyltransferase 1C (Cpt1c), and O-linked N-acetylglucosamine transferase (Ogt) were measured. 26784927 0 19 theme Genes 123:127 arg1 AgRP 133:136 AgRP 133:136 AgRP 133:136 Glucose Alters Per2 Rhythmicity Independent of AMPK, Whereas AMPK Inhibitor Compound C Causes Profound Repression of Clock Genes and AgRP in mHypoE-37 Hypothalamic Neurons. 26784927 0 19 theme Genes 123:127 arg1 Repression 103:112 Profound Repression 94:112 Profound Repression of Clock Genes 94:127 Glucose Alters Per2 Rhythmicity Independent of AMPK, Whereas AMPK Inhibitor Compound C Causes Profound Repression of Clock Genes and AgRP in mHypoE-37 Hypothalamic Neurons. 26784927 12 20 theme AMPK-independent 1795:1810 arg1 repression 1812:1821 AMPK-independent repression 1795:1821 AMPK-independent repression of specific genes 1795:1839 Importantly, the effects of the most commonly used AMPK inhibitor Compound C should be interpreted with caution, considering its role in AMPK-independent repression of specific genes, and especially clock gene rhythm dysregulation. 26784927 12 21 theme AMPK 1709:1712 arg1 C 1733:1733 the most commonly used AMPK inhibitor Compound C 1686:1733 the most commonly used AMPK inhibitor Compound C 1686:1733 Importantly, the effects of the most commonly used AMPK inhibitor Compound C should be interpreted with caution, considering its role in AMPK-independent repression of specific genes, and especially clock gene rhythm dysregulation. 26784927 6 22 with Incubation 680:689 arg1 glucose 703:709 5.5 mM glucose 696:709 5.5 mM glucose 696:709 Incubation with 5.5 mM glucose significantly shortened the period and delayed the phase of Per2 mRNA levels, but had no effect on Bmal1. 26784927 11 23 contain have 1601:1604 arg1 consequences 1467:1478 The consequences 1463:1478 The consequences of inhibition of the rhythmic expression of clock genes, and in turn downstream metabolic mediators, such as AgRP, 1463:1593 The consequences of inhibition of the rhythmic expression of clock genes, and in turn downstream metabolic mediators, such as AgRP, could have detrimental effects on overall metabolic processes. 26784927 11 23 contain have 1601:1604 arg2 effects 1618:1624 detrimental effects 1606:1624 detrimental effects 1606:1624 The consequences of inhibition of the rhythmic expression of clock genes, and in turn downstream metabolic mediators, such as AgRP, could have detrimental effects on overall metabolic processes. 26784927 0 24 theme Inhibitor 66:74 arg1 C 85:85 AMPK Inhibitor Compound C 61:85 AMPK Inhibitor Compound C 61:85 Glucose Alters Per2 Rhythmicity Independent of AMPK, Whereas AMPK Inhibitor Compound C Causes Profound Repression of Clock Genes and AgRP in mHypoE-37 Hypothalamic Neurons. 26784927 8 25 theme mRNA 965:968 arg1 levels 970:975 mRNA levels 965:975 mRNA levels of Per2, Bmal1, Cryptochrome1 (Cry1), agouti-related peptide (AgRP), carnitine palmitoyltransferase 1C (Cpt1c), and O-linked N-acetylglucosamine transferase (Ogt) 965:1138 Thus, the AMPK inhibitor Compound C was utilized, and mRNA levels of Per2, Bmal1, Cryptochrome1 (Cry1), agouti-related peptide (AgRP), carnitine palmitoyltransferase 1C (Cpt1c), and O-linked N-acetylglucosamine transferase (Ogt) were measured. 26784927 4 26 theme mHypoE-37 510:518 arg1 neurons 520:526 mHypoE-37 neurons 510:526 mHypoE-37 neurons 510:526 mHypoE-37 neurons were exposed to 0.5 or 5.5 mM glucose, comparable to physiological levels in the brain. 26784927 9 27 theme Per2 1220:1223 arg1 levels 1210:1215 transcript levels 1199:1215 transcript levels of Per2, Bmal1, Cry1, and AgRP, but not Cpt1c or Ogt 1199:1268 Remarkably, Compound C dramatically reduced transcript levels of Per2, Bmal1, Cry1, and AgRP, but not Cpt1c or Ogt. 26784927 11 28 from turn 1544:1547 arg1 consequences 1467:1478 The consequences 1463:1478 The consequences of inhibition of the rhythmic expression of clock genes, and in turn downstream metabolic mediators, such as AgRP, 1463:1593 The consequences of inhibition of the rhythmic expression of clock genes, and in turn downstream metabolic mediators, such as AgRP, could have detrimental effects on overall metabolic processes. 26784927 0 29 theme Profound 94:101 arg1 Repression 103:112 Profound Repression 94:112 Profound Repression of Clock Genes 94:127 Glucose Alters Per2 Rhythmicity Independent of AMPK, Whereas AMPK Inhibitor Compound C Causes Profound Repression of Clock Genes and AgRP in mHypoE-37 Hypothalamic Neurons. 26784927 9 30 theme Bmal1 1226:1230 arg1 levels 1210:1215 transcript levels 1199:1215 transcript levels of Per2, Bmal1, Cry1, and AgRP, but not Cpt1c or Ogt 1199:1268 Remarkably, Compound C dramatically reduced transcript levels of Per2, Bmal1, Cry1, and AgRP, but not Cpt1c or Ogt. 26784927 12 31 theme C 1733:1733 arg1 effects 1675:1681 the effects 1671:1681 the effects of the most commonly used AMPK inhibitor Compound C 1671:1733 Importantly, the effects of the most commonly used AMPK inhibitor Compound C should be interpreted with caution, considering its role in AMPK-independent repression of specific genes, and especially clock gene rhythm dysregulation. 26784927 11 32 dep expression 1510:1519 arg1 mediators 1570:1578 downstream metabolic mediators 1549:1578 downstream metabolic mediators 1549:1578 The consequences of inhibition of the rhythmic expression of clock genes, and in turn downstream metabolic mediators, such as AgRP, could have detrimental effects on overall metabolic processes. 26784927 3 33 theme cell 428:431 arg1 line 433:436 the immortalized, hypothalamic cell line mHypoE-37 397:446 line 433:436 We have therefore utilized the immortalized, hypothalamic cell line mHypoE-37, which exhibits robust circadian rhythms of core clock genes. 26784927 12 34 theme Compound 1724:1731 arg1 C 1733:1733 the most commonly used AMPK inhibitor Compound C 1686:1733 the most commonly used AMPK inhibitor Compound C 1686:1733 Importantly, the effects of the most commonly used AMPK inhibitor Compound C should be interpreted with caution, considering its role in AMPK-independent repression of specific genes, and especially clock gene rhythm dysregulation. 26784927 9 35 theme Cry1 1233:1236 arg1 levels 1210:1215 transcript levels 1199:1215 transcript levels of Per2, Bmal1, Cry1, and AgRP, but not Cpt1c or Ogt 1199:1268 Remarkably, Compound C dramatically reduced transcript levels of Per2, Bmal1, Cry1, and AgRP, but not Cpt1c or Ogt. 26784927 7 36 theme AMPK 877:880 arg1 phosphorylation 882:896 AMPK phosphorylation 877:896 AMPK phosphorylation 877:896 Glucose had no significant effect on phospho-GSK3β, whereas AMPK phosphorylation was altered. 26784927 3 37 theme robust 464:469 arg1 rhythms 481:487 robust circadian rhythms 464:487 robust circadian rhythms of core clock genes 464:507 We have therefore utilized the immortalized, hypothalamic cell line mHypoE-37, which exhibits robust circadian rhythms of core clock genes. 26784927 0 38 theme Per2 15:18 arg1 Rhythmicity 20:30 Per2 Rhythmicity 15:30 Per2 Rhythmicity Independent of AMPK 15:50 Glucose Alters Per2 Rhythmicity Independent of AMPK, Whereas AMPK Inhibitor Compound C Causes Profound Repression of Clock Genes and AgRP in mHypoE-37 Hypothalamic Neurons. 26784927 12 39 theme used 1704:1707 arg1 C 1733:1733 the most commonly used AMPK inhibitor Compound C 1686:1733 the most commonly used AMPK inhibitor Compound C 1686:1733 Importantly, the effects of the most commonly used AMPK inhibitor Compound C should be interpreted with caution, considering its role in AMPK-independent repression of specific genes, and especially clock gene rhythm dysregulation. 26784927 11 40 theme downstream 1549:1558 arg1 mediators 1570:1578 downstream metabolic mediators 1549:1578 downstream metabolic mediators 1549:1578 The consequences of inhibition of the rhythmic expression of clock genes, and in turn downstream metabolic mediators, such as AgRP, could have detrimental effects on overall metabolic processes. 26784927 0 41 theme Independent 32:42 arg1 Rhythmicity 20:30 Per2 Rhythmicity 15:30 Per2 Rhythmicity Independent of AMPK 15:50 Glucose Alters Per2 Rhythmicity Independent of AMPK, Whereas AMPK Inhibitor Compound C Causes Profound Repression of Clock Genes and AgRP in mHypoE-37 Hypothalamic Neurons. 26784927 12 42 theme inhibitor 1714:1722 arg1 C 1733:1733 the most commonly used AMPK inhibitor Compound C 1686:1733 the most commonly used AMPK inhibitor Compound C 1686:1733 Importantly, the effects of the most commonly used AMPK inhibitor Compound C should be interpreted with caution, considering its role in AMPK-independent repression of specific genes, and especially clock gene rhythm dysregulation. 26784927 3 43 theme core 492:495 arg1 genes 503:507 core clock genes 492:507 core clock genes 492:507 We have therefore utilized the immortalized, hypothalamic cell line mHypoE-37, which exhibits robust circadian rhythms of core clock genes. 26784927 0 44 theme AMPK 47:50 arg1 Independent 32:42 Independent 32:42 Independent 32:42 Glucose Alters Per2 Rhythmicity Independent of AMPK, Whereas AMPK Inhibitor Compound C Causes Profound Repression of Clock Genes and AgRP in mHypoE-37 Hypothalamic Neurons. 26784927 8 45 theme agouti-related 1015:1028 arg1 peptide 1030:1036 agouti-related peptide 1015:1036 agouti-related peptide (AgRP) 1015:1043 Thus, the AMPK inhibitor Compound C was utilized, and mRNA levels of Per2, Bmal1, Cryptochrome1 (Cry1), agouti-related peptide (AgRP), carnitine palmitoyltransferase 1C (Cpt1c), and O-linked N-acetylglucosamine transferase (Ogt) were measured. 26784927 8 45 theme agouti-related 1015:1028 arg1 AgRP 1039:1042 AgRP 1039:1042 AgRP 1039:1042 Thus, the AMPK inhibitor Compound C was utilized, and mRNA levels of Per2, Bmal1, Cryptochrome1 (Cry1), agouti-related peptide (AgRP), carnitine palmitoyltransferase 1C (Cpt1c), and O-linked N-acetylglucosamine transferase (Ogt) were measured. 26784927 12 46 from role 1787:1790 arg1 repression 1812:1821 AMPK-independent repression 1795:1821 AMPK-independent repression of specific genes 1795:1839 Importantly, the effects of the most commonly used AMPK inhibitor Compound C should be interpreted with caution, considering its role in AMPK-independent repression of specific genes, and especially clock gene rhythm dysregulation. 26784927 11 47 theme inhibition 1483:1492 arg1 consequences 1467:1478 The consequences 1463:1478 The consequences of inhibition of the rhythmic expression of clock genes, and in turn downstream metabolic mediators, such as AgRP, 1463:1593 The consequences of inhibition of the rhythmic expression of clock genes, and in turn downstream metabolic mediators, such as AgRP, could have detrimental effects on overall metabolic processes. 26784927 1 48 theme peripheral 227:236 arg1 hormones 238:245 peripheral hormones 227:245 peripheral hormones 227:245 Specific neurons in the hypothalamus are regulated by peripheral hormones and nutrients to maintain proper metabolic control. 26784927 12 49 theme gene 1863:1866 arg1 dysregulation 1875:1887 clock gene rhythm dysregulation 1857:1887 clock gene rhythm dysregulation 1857:1887 Importantly, the effects of the most commonly used AMPK inhibitor Compound C should be interpreted with caution, considering its role in AMPK-independent repression of specific genes, and especially clock gene rhythm dysregulation. 26784927 10 50 theme Compound 1387:1394 arg1 C 1396:1396 Compound C 1387:1396 Compound C 1387:1396 Because AMPK was not inhibited at the same time or concentrations as the clock genes, we suggest that the effect of Compound C on gene expression occurs through an AMPK-independent mechanism. 26784927 11 51 theme expression 1510:1519 arg1 inhibition 1483:1492 inhibition 1483:1492 inhibition of the rhythmic expression of clock genes, and in turn downstream metabolic mediators, such as AgRP, 1483:1593 The consequences of inhibition of the rhythmic expression of clock genes, and in turn downstream metabolic mediators, such as AgRP, could have detrimental effects on overall metabolic processes. 26784927 6 52 theme 5.5 696:698 arg1 mM 700:701 mM 700:701 mM 700:701 Incubation with 5.5 mM glucose significantly shortened the period and delayed the phase of Per2 mRNA levels, but had no effect on Bmal1. 26784927 2 53 theme gene 353:356 arg1 expression 358:367 clock gene expression 347:367 clock gene expression 347:367 It is unclear if nutrients can directly control clock gene expression. 26784927 8 54 theme carnitine 1046:1054 arg1 palmitoyltransferase 1056:1075 carnitine palmitoyltransferase 1C 1046:1078 carnitine palmitoyltransferase 1C (Cpt1c) 1046:1086 Thus, the AMPK inhibitor Compound C was utilized, and mRNA levels of Per2, Bmal1, Cryptochrome1 (Cry1), agouti-related peptide (AgRP), carnitine palmitoyltransferase 1C (Cpt1c), and O-linked N-acetylglucosamine transferase (Ogt) were measured. 26784927 8 54 theme carnitine 1046:1054 arg1 Cpt1c 1081:1085 Cpt1c 1081:1085 Cpt1c 1081:1085 Thus, the AMPK inhibitor Compound C was utilized, and mRNA levels of Per2, Bmal1, Cryptochrome1 (Cry1), agouti-related peptide (AgRP), carnitine palmitoyltransferase 1C (Cpt1c), and O-linked N-acetylglucosamine transferase (Ogt) were measured. 26784927 8 55 theme inhibitor 926:934 arg1 C 945:945 the AMPK inhibitor Compound C 917:945 the AMPK inhibitor Compound C 917:945 Thus, the AMPK inhibitor Compound C was utilized, and mRNA levels of Per2, Bmal1, Cryptochrome1 (Cry1), agouti-related peptide (AgRP), carnitine palmitoyltransferase 1C (Cpt1c), and O-linked N-acetylglucosamine transferase (Ogt) were measured. 26784927 6 56 theme levels 781:786 arg1 phase 762:766 the phase 758:766 the phase of Per2 mRNA levels 758:786 Incubation with 5.5 mM glucose significantly shortened the period and delayed the phase of Per2 mRNA levels, but had no effect on Bmal1. 26784927 4 57 from levels 595:600 arg1 brain 609:613 the brain 605:613 the brain 605:613 mHypoE-37 neurons were exposed to 0.5 or 5.5 mM glucose, comparable to physiological levels in the brain. 26784927 6 58 theme Per2 771:774 arg1 levels 781:786 Per2 mRNA levels 771:786 Per2 mRNA levels 771:786 Incubation with 5.5 mM glucose significantly shortened the period and delayed the phase of Per2 mRNA levels, but had no effect on Bmal1. 26784927 5 59 dep Per2 616:619 arg1 mRNAs 631:635 mRNAs 631:635 mRNAs 631:635 Per2 and Bmal1 mRNAs were assessed every 3 hours over 36 hours. 26784927 11 60 theme clock 1524:1528 arg1 genes 1530:1534 clock genes 1524:1534 clock genes 1524:1534 The consequences of inhibition of the rhythmic expression of clock genes, and in turn downstream metabolic mediators, such as AgRP, could have detrimental effects on overall metabolic processes. 26784927 1 61 theme Specific 173:180 arg1 neurons 182:188 Specific neurons 173:188 Specific neurons in the hypothalamus 173:208 Specific neurons in the hypothalamus are regulated by peripheral hormones and nutrients to maintain proper metabolic control. 26784927 10 62 theme same 1309:1312 arg1 time 1314:1317 the same time 1305:1317 the same time 1305:1317 Because AMPK was not inhibited at the same time or concentrations as the clock genes, we suggest that the effect of Compound C on gene expression occurs through an AMPK-independent mechanism. 26784927 10 63 theme AMPK-independent 1435:1450 arg1 mechanism 1452:1460 an AMPK-independent mechanism 1432:1460 an AMPK-independent mechanism 1432:1460 Because AMPK was not inhibited at the same time or concentrations as the clock genes, we suggest that the effect of Compound C on gene expression occurs through an AMPK-independent mechanism. 26784927 0 64 theme Clock 117:121 arg1 Genes 123:127 Clock Genes 117:127 Clock Genes 117:127 Glucose Alters Per2 Rhythmicity Independent of AMPK, Whereas AMPK Inhibitor Compound C Causes Profound Repression of Clock Genes and AgRP in mHypoE-37 Hypothalamic Neurons. 26784927 8 65 theme O-linked 1093:1100 arg1 Ogt 1135:1137 Ogt 1135:1137 Ogt 1135:1137 Thus, the AMPK inhibitor Compound C was utilized, and mRNA levels of Per2, Bmal1, Cryptochrome1 (Cry1), agouti-related peptide (AgRP), carnitine palmitoyltransferase 1C (Cpt1c), and O-linked N-acetylglucosamine transferase (Ogt) were measured. 26784927 8 65 theme O-linked 1093:1100 arg1 transferase 1122:1132 O-linked N-acetylglucosamine transferase 1093:1132 O-linked N-acetylglucosamine transferase (Ogt) 1093:1138 Thus, the AMPK inhibitor Compound C was utilized, and mRNA levels of Per2, Bmal1, Cryptochrome1 (Cry1), agouti-related peptide (AgRP), carnitine palmitoyltransferase 1C (Cpt1c), and O-linked N-acetylglucosamine transferase (Ogt) were measured. 26784927 11 66 theme metabolic 1637:1645 arg1 processes 1647:1655 overall metabolic processes 1629:1655 overall metabolic processes 1629:1655 The consequences of inhibition of the rhythmic expression of clock genes, and in turn downstream metabolic mediators, such as AgRP, could have detrimental effects on overall metabolic processes. 26784927 8 67 theme transferase 1122:1132 arg1 levels 970:975 mRNA levels 965:975 mRNA levels of Per2, Bmal1, Cryptochrome1 (Cry1), agouti-related peptide (AgRP), carnitine palmitoyltransferase 1C (Cpt1c), and O-linked N-acetylglucosamine transferase (Ogt) 965:1138 Thus, the AMPK inhibitor Compound C was utilized, and mRNA levels of Per2, Bmal1, Cryptochrome1 (Cry1), agouti-related peptide (AgRP), carnitine palmitoyltransferase 1C (Cpt1c), and O-linked N-acetylglucosamine transferase (Ogt) were measured. 26784927 12 68 theme genes 1835:1839 arg1 repression 1812:1821 AMPK-independent repression 1795:1821 AMPK-independent repression of specific genes 1795:1839 Importantly, the effects of the most commonly used AMPK inhibitor Compound C should be interpreted with caution, considering its role in AMPK-independent repression of specific genes, and especially clock gene rhythm dysregulation. 26784927 0 69 theme Hypothalamic 151:162 arg1 Neurons 164:170 mHypoE-37 Hypothalamic Neurons 141:170 mHypoE-37 Hypothalamic Neurons 141:170 Glucose Alters Per2 Rhythmicity Independent of AMPK, Whereas AMPK Inhibitor Compound C Causes Profound Repression of Clock Genes and AgRP in mHypoE-37 Hypothalamic Neurons. 26784927 9 70 theme Compound 1167:1174 arg1 C 1176:1176 Compound C 1167:1176 Compound C 1167:1176 Remarkably, Compound C dramatically reduced transcript levels of Per2, Bmal1, Cry1, and AgRP, but not Cpt1c or Ogt. 26784927 0 71 theme AMPK 61:64 arg1 C 85:85 AMPK Inhibitor Compound C 61:85 AMPK Inhibitor Compound C 61:85 Glucose Alters Per2 Rhythmicity Independent of AMPK, Whereas AMPK Inhibitor Compound C Causes Profound Repression of Clock Genes and AgRP in mHypoE-37 Hypothalamic Neurons. 26784927 1 72 from neurons 182:188 arg1 hypothalamus 197:208 the hypothalamus 193:208 the hypothalamus 193:208 Specific neurons in the hypothalamus are regulated by peripheral hormones and nutrients to maintain proper metabolic control. 26784927 12 73 theme specific 1826:1833 arg1 genes 1835:1839 specific genes 1826:1839 specific genes 1826:1839 Importantly, the effects of the most commonly used AMPK inhibitor Compound C should be interpreted with caution, considering its role in AMPK-independent repression of specific genes, and especially clock gene rhythm dysregulation. 26784927 6 74 contain had 793:795 arg2 effect 800:805 no effect 797:805 no effect 797:805 Incubation with 5.5 mM glucose significantly shortened the period and delayed the phase of Per2 mRNA levels, but had no effect on Bmal1. 26784927 6 74 contain had 793:795 arg1 Incubation 680:689 Incubation 680:689 Incubation with 5.5 mM glucose 680:709 Incubation with 5.5 mM glucose significantly shortened the period and delayed the phase of Per2 mRNA levels, but had no effect on Bmal1. 26784927 0 75 theme Compound 76:83 arg1 C 85:85 AMPK Inhibitor Compound C 61:85 AMPK Inhibitor Compound C 61:85 Glucose Alters Per2 Rhythmicity Independent of AMPK, Whereas AMPK Inhibitor Compound C Causes Profound Repression of Clock Genes and AgRP in mHypoE-37 Hypothalamic Neurons. 26784927 9 76 theme transcript 1199:1208 arg1 levels 1210:1215 transcript levels 1199:1215 transcript levels of Per2, Bmal1, Cry1, and AgRP, but not Cpt1c or Ogt 1199:1268 Remarkably, Compound C dramatically reduced transcript levels of Per2, Bmal1, Cry1, and AgRP, but not Cpt1c or Ogt. 26784927 4 77 dep glucose 558:564 arg1 mM 555:556 mM 555:556 mM 555:556 mHypoE-37 neurons were exposed to 0.5 or 5.5 mM glucose, comparable to physiological levels in the brain. 26784927 7 78 contain had 825:827 arg2 effect 844:849 no significant effect 829:849 no significant effect 829:849 Glucose had no significant effect on phospho-GSK3β, whereas AMPK phosphorylation was altered. 26784927 7 78 contain had 825:827 arg1 Glucose 817:823 Glucose 817:823 Glucose 817:823 Glucose had no significant effect on phospho-GSK3β, whereas AMPK phosphorylation was altered. 26784927 8 79 theme Per2 980:983 arg1 levels 970:975 mRNA levels 965:975 mRNA levels of Per2, Bmal1, Cryptochrome1 (Cry1), agouti-related peptide (AgRP), carnitine palmitoyltransferase 1C (Cpt1c), and O-linked N-acetylglucosamine transferase (Ogt) 965:1138 Thus, the AMPK inhibitor Compound C was utilized, and mRNA levels of Per2, Bmal1, Cryptochrome1 (Cry1), agouti-related peptide (AgRP), carnitine palmitoyltransferase 1C (Cpt1c), and O-linked N-acetylglucosamine transferase (Ogt) were measured. 26784927 8 80 link O-linked 1093:1100 arg1 Ogt 1135:1137 Ogt 1135:1137 Ogt 1135:1137 Thus, the AMPK inhibitor Compound C was utilized, and mRNA levels of Per2, Bmal1, Cryptochrome1 (Cry1), agouti-related peptide (AgRP), carnitine palmitoyltransferase 1C (Cpt1c), and O-linked N-acetylglucosamine transferase (Ogt) were measured. 26784927 8 80 link O-linked 1093:1100 arg1 transferase 1122:1132 O-linked N-acetylglucosamine transferase 1093:1132 O-linked N-acetylglucosamine transferase (Ogt) 1093:1138 Thus, the AMPK inhibitor Compound C was utilized, and mRNA levels of Per2, Bmal1, Cryptochrome1 (Cry1), agouti-related peptide (AgRP), carnitine palmitoyltransferase 1C (Cpt1c), and O-linked N-acetylglucosamine transferase (Ogt) were measured. 26784927 10 81 from effect 1377:1382 arg1 expression 1406:1415 gene expression 1401:1415 gene expression 1401:1415 Because AMPK was not inhibited at the same time or concentrations as the clock genes, we suggest that the effect of Compound C on gene expression occurs through an AMPK-independent mechanism. 26784927 11 82 theme detrimental 1606:1616 arg1 effects 1618:1624 detrimental effects 1606:1624 detrimental effects 1606:1624 The consequences of inhibition of the rhythmic expression of clock genes, and in turn downstream metabolic mediators, such as AgRP, could have detrimental effects on overall metabolic processes. 26784927 4 83 dep mM 555:556 arg1 5.5 551:553 5.5 551:553 5.5 551:553 mHypoE-37 neurons were exposed to 0.5 or 5.5 mM glucose, comparable to physiological levels in the brain. 26784927 4 83 dep mM 555:556 arg1 0.5 544:546 0.5 544:546 0.5 544:546 mHypoE-37 neurons were exposed to 0.5 or 5.5 mM glucose, comparable to physiological levels in the brain. 26784927 8 84 theme Bmal1 986:990 arg1 levels 970:975 mRNA levels 965:975 mRNA levels of Per2, Bmal1, Cryptochrome1 (Cry1), agouti-related peptide (AgRP), carnitine palmitoyltransferase 1C (Cpt1c), and O-linked N-acetylglucosamine transferase (Ogt) 965:1138 Thus, the AMPK inhibitor Compound C was utilized, and mRNA levels of Per2, Bmal1, Cryptochrome1 (Cry1), agouti-related peptide (AgRP), carnitine palmitoyltransferase 1C (Cpt1c), and O-linked N-acetylglucosamine transferase (Ogt) were measured. 26784927 8 85 theme Cryptochrome1 993:1005 arg1 Cry1 1008:1011 Cryptochrome1 (Cry1) 993:1012 Cryptochrome1 (Cry1) 993:1012 Thus, the AMPK inhibitor Compound C was utilized, and mRNA levels of Per2, Bmal1, Cryptochrome1 (Cry1), agouti-related peptide (AgRP), carnitine palmitoyltransferase 1C (Cpt1c), and O-linked N-acetylglucosamine transferase (Ogt) were measured. 26784927 1 86 theme metabolic 280:288 arg1 control 290:296 proper metabolic control 273:296 proper metabolic control 273:296 Specific neurons in the hypothalamus are regulated by peripheral hormones and nutrients to maintain proper metabolic control. 26784927 8 87 theme Cry1 1008:1011 arg1 levels 970:975 mRNA levels 965:975 mRNA levels of Per2, Bmal1, Cryptochrome1 (Cry1), agouti-related peptide (AgRP), carnitine palmitoyltransferase 1C (Cpt1c), and O-linked N-acetylglucosamine transferase (Ogt) 965:1138 Thus, the AMPK inhibitor Compound C was utilized, and mRNA levels of Per2, Bmal1, Cryptochrome1 (Cry1), agouti-related peptide (AgRP), carnitine palmitoyltransferase 1C (Cpt1c), and O-linked N-acetylglucosamine transferase (Ogt) were measured. 26784927 3 88 theme circadian 471:479 arg1 rhythms 481:487 robust circadian rhythms 464:487 robust circadian rhythms of core clock genes 464:507 We have therefore utilized the immortalized, hypothalamic cell line mHypoE-37, which exhibits robust circadian rhythms of core clock genes. 26784927 9 89 theme AgRP 1243:1246 arg1 levels 1210:1215 transcript levels 1199:1215 transcript levels of Per2, Bmal1, Cry1, and AgRP, but not Cpt1c or Ogt 1199:1268 Remarkably, Compound C dramatically reduced transcript levels of Per2, Bmal1, Cry1, and AgRP, but not Cpt1c or Ogt. 26784927 3 90 used utilized 388:395 arg2 We 370:371 We 370:371 We 370:371 We have therefore utilized the immortalized, hypothalamic cell line mHypoE-37, which exhibits robust circadian rhythms of core clock genes. 26784927 3 91 theme hypothalamic 415:426 arg1 line 433:436 the immortalized, hypothalamic cell line mHypoE-37 397:446 line 433:436 We have therefore utilized the immortalized, hypothalamic cell line mHypoE-37, which exhibits robust circadian rhythms of core clock genes. 26784927 10 92 theme clock 1344:1348 arg1 genes 1350:1354 the clock genes 1340:1354 the clock genes 1340:1354 Because AMPK was not inhibited at the same time or concentrations as the clock genes, we suggest that the effect of Compound C on gene expression occurs through an AMPK-independent mechanism. 26784927 8 93 theme peptide 1030:1036 arg1 levels 970:975 mRNA levels 965:975 mRNA levels of Per2, Bmal1, Cryptochrome1 (Cry1), agouti-related peptide (AgRP), carnitine palmitoyltransferase 1C (Cpt1c), and O-linked N-acetylglucosamine transferase (Ogt) 965:1138 Thus, the AMPK inhibitor Compound C was utilized, and mRNA levels of Per2, Bmal1, Cryptochrome1 (Cry1), agouti-related peptide (AgRP), carnitine palmitoyltransferase 1C (Cpt1c), and O-linked N-acetylglucosamine transferase (Ogt) were measured. 26784927 3 94 theme immortalized 401:412 arg1 line 433:436 the immortalized, hypothalamic cell line mHypoE-37 397:446 line 433:436 We have therefore utilized the immortalized, hypothalamic cell line mHypoE-37, which exhibits robust circadian rhythms of core clock genes. 26784927 3 95 theme clock 497:501 arg1 genes 503:507 core clock genes 492:507 core clock genes 492:507 We have therefore utilized the immortalized, hypothalamic cell line mHypoE-37, which exhibits robust circadian rhythms of core clock genes. 26784927 9 96 theme Cpt1c 1257:1261 arg1 levels 1210:1215 transcript levels 1199:1215 transcript levels of Per2, Bmal1, Cry1, and AgRP, but not Cpt1c or Ogt 1199:1268 Remarkably, Compound C dramatically reduced transcript levels of Per2, Bmal1, Cry1, and AgRP, but not Cpt1c or Ogt. 26784927 11 97 theme metabolic 1560:1568 arg1 mediators 1570:1578 downstream metabolic mediators 1549:1578 downstream metabolic mediators 1549:1578 The consequences of inhibition of the rhythmic expression of clock genes, and in turn downstream metabolic mediators, such as AgRP, could have detrimental effects on overall metabolic processes. 26784927 12 98 theme rhythm 1868:1873 arg1 dysregulation 1875:1887 clock gene rhythm dysregulation 1857:1887 clock gene rhythm dysregulation 1857:1887 Importantly, the effects of the most commonly used AMPK inhibitor Compound C should be interpreted with caution, considering its role in AMPK-independent repression of specific genes, and especially clock gene rhythm dysregulation. 26784927 0 99 dep Alters 8:13 arg1 Whereas 53:59 Whereas 53:59 Whereas 53:59 Glucose Alters Per2 Rhythmicity Independent of AMPK, Whereas AMPK Inhibitor Compound C Causes Profound Repression of Clock Genes and AgRP in mHypoE-37 Hypothalamic Neurons. 26784927 10 100 theme C 1396:1396 arg1 effect 1377:1382 the effect 1373:1382 the effect of Compound C on gene expression 1373:1415 Because AMPK was not inhibited at the same time or concentrations as the clock genes, we suggest that the effect of Compound C on gene expression occurs through an AMPK-independent mechanism. 26784927 11 101 theme rhythmic 1501:1508 arg1 expression 1510:1519 the rhythmic expression 1497:1519 the rhythmic expression of clock genes 1497:1534 The consequences of inhibition of the rhythmic expression of clock genes, and in turn downstream metabolic mediators, such as AgRP, could have detrimental effects on overall metabolic processes. 26784927 6 102 theme mM 700:701 arg1 glucose 703:709 5.5 mM glucose 696:709 5.5 mM glucose 696:709 Incubation with 5.5 mM glucose significantly shortened the period and delayed the phase of Per2 mRNA levels, but had no effect on Bmal1. 26784927 7 103 theme significant 832:842 arg1 effect 844:849 no significant effect 829:849 no significant effect 829:849 Glucose had no significant effect on phospho-GSK3β, whereas AMPK phosphorylation was altered. 26724145 9 0 theme Ki67 1659:1662 arg1 LI 1664:1665 Ki67 LI 1659:1665 Ki67 LI 1659:1665 O-GlcNAcylation expression decreased in metastatic nodal lesions compared to the invasive front and tumor center, and was inversely correlated with Ki67 LI. 26724145 5 1 dep RESULTS 1059:1065 arg1 showed 1138:1143 showed 1138:1143 showed greater increases in metastatic nodal lesions 1138:1189 Western blot was also conducted in primary CRC tissue RESULTS Membranous E-cadherin expression was lowest in the invasive front, but showed greater increases in metastatic nodal lesions. 26724145 5 1 dep RESULTS 1059:1065 arg1 lowest 1104:1109 lowest 1104:1109 lowest 1104:1109 Western blot was also conducted in primary CRC tissue RESULTS Membranous E-cadherin expression was lowest in the invasive front, but showed greater increases in metastatic nodal lesions. 26724145 3 2 theme expression 690:699 arg1 levels 701:706 O-GlcNAcylation expression levels 674:706 O-GlcNAcylation expression levels in those areas 674:721 The current study examined the status of EMT/MET in both the tumor center and invasive front of the primary colorectal carcinoma (CRC) and metastatic nodal lesions, which were compared to O-GlcNAcylation expression levels in those areas. 26724145 2 3 theme mesenchymal 376:386 arg1 transition 388:397 epithelial to mesenchymal transition 362:397 epithelial to mesenchymal transition (EMT)/mesenchymal to epithelial transition (MET) 362:446 The E-cadherin/β-catenin system, an integral component of epithelial to mesenchymal transition (EMT)/mesenchymal to epithelial transition (MET), is affected through O-GlcNAcylation. 26724145 2 3 theme mesenchymal 376:386 arg1 EMT 400:402 EMT 400:402 EMT 400:402 The E-cadherin/β-catenin system, an integral component of epithelial to mesenchymal transition (EMT)/mesenchymal to epithelial transition (MET), is affected through O-GlcNAcylation. 26724145 1 4 theme serine 275:280 arg1 residue 295:301 a serine or threonine residue 273:301 residue 295:301 INTRODUCTION O-GlcNAcylation is an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety linked to the side chain hydroxyl of a serine or threonine residue. 26724145 13 5 theme membranous 2032:2041 arg1 expression 2054:2063 Differential membranous E-cadherin expression 2019:2063 Differential membranous E-cadherin expression 2019:2063 CONCLUSIONS Differential membranous E-cadherin expression, cell proliferation and O-GlcNAcylation in metastatic nodal lesion compared to primary CRC may play role in establishing its lesions; however, these findings are not sufficient to show the role of O-GlcNAcylation in the EMT/MET of CRC. 26724145 11 6 theme E-cadherin 1879:1888 arg1 expression 1821:1830 its expression 1817:1830 its expression 1817:1830 In addition, there was no correlation between its expression and the level of nuclear β-catenin, membranous E-cadherin and Snail. 26724145 11 6 theme E-cadherin 1879:1888 arg1 level 1840:1844 the level 1836:1844 the level of nuclear β-catenin, membranous E-cadherin and Snail 1836:1898 In addition, there was no correlation between its expression and the level of nuclear β-catenin, membranous E-cadherin and Snail. 26724145 1 7 theme threonine 285:293 arg1 residue 295:301 a serine or threonine residue 273:301 residue 295:301 INTRODUCTION O-GlcNAcylation is an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety linked to the side chain hydroxyl of a serine or threonine residue. 26724145 3 8 theme tumor 547:551 arg1 center 553:558 the tumor center 543:558 the tumor center 543:558 The current study examined the status of EMT/MET in both the tumor center and invasive front of the primary colorectal carcinoma (CRC) and metastatic nodal lesions, which were compared to O-GlcNAcylation expression levels in those areas. 26724145 13 9 from proliferation 2071:2083 arg1 lesion 2125:2130 metastatic nodal lesion 2108:2130 metastatic nodal lesion compared to primary CRC 2108:2154 CONCLUSIONS Differential membranous E-cadherin expression, cell proliferation and O-GlcNAcylation in metastatic nodal lesion compared to primary CRC may play role in establishing its lesions; however, these findings are not sufficient to show the role of O-GlcNAcylation in the EMT/MET of CRC. 26724145 4 10 dep MATERIAL 804:811 arg1 performed 910:918 performed 910:918 was performed in 40 primary CRC tissues, 40 nonneoplastic colons, and 17 nodal metastatic lesions 906:1002 In addition, the cliniopathological significance of O-GlcNAcylation was studied MATERIAL AND METHODS Immunohistochemical staining for E-cadherin, β-catenin, Snail, O-GlcNAc and Ki67 was performed in 40 primary CRC tissues, 40 nonneoplastic colons, and 17 nodal metastatic lesions. 26724145 7 11 theme nodal 1382:1386 arg1 lesions 1388:1394 metastatic nodal lesions 1371:1394 metastatic nodal lesions 1371:1394 The Ki67 labeling index (LI) was lowest in the invasive front, and increased in metastatic nodal lesions. 26724145 0 12 theme colorectal 133:142 arg1 cancer 144:149 colorectal cancer 133:149 colorectal cancer 133:149 Differential membranous E-cadherin expression, cell proliferation and O-GlcNAcylation between primary and metastatic nodal lesion in colorectal cancer. 26724145 5 13 theme E-cadherin 1078:1087 arg1 expression 1089:1098 Membranous E-cadherin expression 1067:1098 Membranous E-cadherin expression 1067:1098 Western blot was also conducted in primary CRC tissue RESULTS Membranous E-cadherin expression was lowest in the invasive front, but showed greater increases in metastatic nodal lesions. 26724145 3 14 theme EMT/MET 527:533 arg1 status 517:522 the status 513:522 the status of EMT/MET in both the tumor center and invasive front of the primary colorectal carcinoma (CRC) and metastatic nodal lesions, which were compared to O-GlcNAcylation expression levels in those areas 513:721 The current study examined the status of EMT/MET in both the tumor center and invasive front of the primary colorectal carcinoma (CRC) and metastatic nodal lesions, which were compared to O-GlcNAcylation expression levels in those areas. 26724145 12 15 theme cliniopathological 1976:1993 arg1 parameters 1995:2004 cliniopathological parameters 1976:2004 cliniopathological parameters 1976:2004 No significant relationship was observed between O-GlcNAcylation level and cliniopathological parameters. 26724145 3 16 from levels 701:706 arg1 areas 717:721 those areas 711:721 those areas 711:721 The current study examined the status of EMT/MET in both the tumor center and invasive front of the primary colorectal carcinoma (CRC) and metastatic nodal lesions, which were compared to O-GlcNAcylation expression levels in those areas. 26724145 13 17 from O-GlcNAcylation 2089:2103 arg1 lesion 2125:2130 metastatic nodal lesion 2108:2130 metastatic nodal lesion compared to primary CRC 2108:2154 CONCLUSIONS Differential membranous E-cadherin expression, cell proliferation and O-GlcNAcylation in metastatic nodal lesion compared to primary CRC may play role in establishing its lesions; however, these findings are not sufficient to show the role of O-GlcNAcylation in the EMT/MET of CRC. 26724145 5 18 theme CRC 1048:1050 arg1 RESULTS 1059:1065 primary CRC tissue RESULTS 1040:1065 primary CRC tissue RESULTS Membranous E-cadherin expression was lowest in the invasive front, but showed greater increases in metastatic nodal lesions 1040:1189 Western blot was also conducted in primary CRC tissue RESULTS Membranous E-cadherin expression was lowest in the invasive front, but showed greater increases in metastatic nodal lesions. 26724145 3 19 theme colorectal 594:603 arg1 carcinoma 605:613 the primary colorectal carcinoma 582:613 the primary colorectal carcinoma (CRC) 582:619 The current study examined the status of EMT/MET in both the tumor center and invasive front of the primary colorectal carcinoma (CRC) and metastatic nodal lesions, which were compared to O-GlcNAcylation expression levels in those areas. 26724145 3 19 theme colorectal 594:603 arg1 CRC 616:618 CRC 616:618 CRC 616:618 The current study examined the status of EMT/MET in both the tumor center and invasive front of the primary colorectal carcinoma (CRC) and metastatic nodal lesions, which were compared to O-GlcNAcylation expression levels in those areas. 26724145 4 20 theme primary 926:932 arg1 tissues 938:944 40 primary CRC tissues 923:944 40 primary CRC tissues 923:944 In addition, the cliniopathological significance of O-GlcNAcylation was studied MATERIAL AND METHODS Immunohistochemical staining for E-cadherin, β-catenin, Snail, O-GlcNAc and Ki67 was performed in 40 primary CRC tissues, 40 nonneoplastic colons, and 17 nodal metastatic lesions. 26724145 0 21 from lesion 123:128 arg1 cancer 144:149 colorectal cancer 133:149 colorectal cancer 133:149 Differential membranous E-cadherin expression, cell proliferation and O-GlcNAcylation between primary and metastatic nodal lesion in colorectal cancer. 26724145 3 22 theme metastatic 625:634 arg1 lesions 642:648 metastatic nodal lesions 625:648 metastatic nodal lesions 625:648 The current study examined the status of EMT/MET in both the tumor center and invasive front of the primary colorectal carcinoma (CRC) and metastatic nodal lesions, which were compared to O-GlcNAcylation expression levels in those areas. 26724145 9 23 theme O-GlcNAcylation 1511:1525 arg1 expression 1527:1536 O-GlcNAcylation expression 1511:1536 O-GlcNAcylation expression 1511:1536 O-GlcNAcylation expression decreased in metastatic nodal lesions compared to the invasive front and tumor center, and was inversely correlated with Ki67 LI. 26724145 13 24 dep CONCLUSIONS 2007:2017 arg1 sufficient 2231:2240 sufficient 2231:2240 sufficient 2231:2240 CONCLUSIONS Differential membranous E-cadherin expression, cell proliferation and O-GlcNAcylation in metastatic nodal lesion compared to primary CRC may play role in establishing its lesions; however, these findings are not sufficient to show the role of O-GlcNAcylation in the EMT/MET of CRC. 26724145 13 24 dep CONCLUSIONS 2007:2017 arg1 play 2160:2163 play 2160:2163 may play role in establishing its lesions 2156:2196 CONCLUSIONS Differential membranous E-cadherin expression, cell proliferation and O-GlcNAcylation in metastatic nodal lesion compared to primary CRC may play role in establishing its lesions; however, these findings are not sufficient to show the role of O-GlcNAcylation in the EMT/MET of CRC. 26724145 4 25 theme nodal 979:983 arg1 lesions 996:1002 17 nodal metastatic lesions 976:1002 17 nodal metastatic lesions 976:1002 In addition, the cliniopathological significance of O-GlcNAcylation was studied MATERIAL AND METHODS Immunohistochemical staining for E-cadherin, β-catenin, Snail, O-GlcNAc and Ki67 was performed in 40 primary CRC tissues, 40 nonneoplastic colons, and 17 nodal metastatic lesions. 26724145 6 26 theme expression 1206:1215 arg1 level 1217:1221 its expression level 1202:1221 its expression level 1202:1221 Moreover, its expression level was negatively correlated with that of nuclear β-catenin and Snail. 26724145 13 27 theme primary 2144:2150 arg1 CRC 2152:2154 primary CRC 2144:2154 primary CRC 2144:2154 CONCLUSIONS Differential membranous E-cadherin expression, cell proliferation and O-GlcNAcylation in metastatic nodal lesion compared to primary CRC may play role in establishing its lesions; however, these findings are not sufficient to show the role of O-GlcNAcylation in the EMT/MET of CRC. 26724145 8 28 theme nonneoplastic 1489:1501 arg1 colons 1503:1508 nonneoplastic colons 1489:1508 nonneoplastic colons 1489:1508 Primary CRC showed higher expression of O-GlcNAcylation and O-GlcNAc-transferase (OGT) than nonneoplastic colons. 26724145 0 29 theme primary 94:100 arg1 lesion 123:128 primary and metastatic nodal lesion 94:128 primary and metastatic nodal lesion in colorectal cancer 94:149 Differential membranous E-cadherin expression, cell proliferation and O-GlcNAcylation between primary and metastatic nodal lesion in colorectal cancer. 26724145 1 30 theme O-linked 187:194 arg1 O-GlcNAcylation 165:179 INTRODUCTION O-GlcNAcylation 152:179 INTRODUCTION O-GlcNAcylation 152:179 INTRODUCTION O-GlcNAcylation is an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety linked to the side chain hydroxyl of a serine or threonine residue. 26724145 1 30 theme O-linked 187:194 arg1 moiety 229:234 an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety 184:234 an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety linked to the side chain hydroxyl of a serine or threonine residue 184:301 INTRODUCTION O-GlcNAcylation is an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety linked to the side chain hydroxyl of a serine or threonine residue. 26724145 10 31 theme tumor 1738:1742 arg1 center 1744:1749 tumor center 1738:1749 tumor center 1738:1749 However, O-GlcNAcylation expression was only slightly changed between tumor center and invasive front. 26724145 4 32 theme O-GlcNAcylation 776:790 arg1 significance 760:771 the cliniopathological significance 737:771 the cliniopathological significance of O-GlcNAcylation 737:790 In addition, the cliniopathological significance of O-GlcNAcylation was studied MATERIAL AND METHODS Immunohistochemical staining for E-cadherin, β-catenin, Snail, O-GlcNAc and Ki67 was performed in 40 primary CRC tissues, 40 nonneoplastic colons, and 17 nodal metastatic lesions. 26724145 0 33 theme metastatic 106:115 arg1 lesion 123:128 primary and metastatic nodal lesion 94:128 primary and metastatic nodal lesion in colorectal cancer 94:149 Differential membranous E-cadherin expression, cell proliferation and O-GlcNAcylation between primary and metastatic nodal lesion in colorectal cancer. 26724145 13 34 theme nodal 2119:2123 arg1 lesion 2125:2130 metastatic nodal lesion 2108:2130 metastatic nodal lesion compared to primary CRC 2108:2154 CONCLUSIONS Differential membranous E-cadherin expression, cell proliferation and O-GlcNAcylation in metastatic nodal lesion compared to primary CRC may play role in establishing its lesions; however, these findings are not sufficient to show the role of O-GlcNAcylation in the EMT/MET of CRC. 26724145 12 35 theme O-GlcNAcylation 1950:1964 arg1 level 1966:1970 O-GlcNAcylation level 1950:1970 O-GlcNAcylation level 1950:1970 No significant relationship was observed between O-GlcNAcylation level and cliniopathological parameters. 26724145 1 36 theme INTRODUCTION 152:163 arg1 moiety 229:234 an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety 184:234 an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety linked to the side chain hydroxyl of a serine or threonine residue 184:301 INTRODUCTION O-GlcNAcylation is an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety linked to the side chain hydroxyl of a serine or threonine residue. 26724145 1 36 theme INTRODUCTION 152:163 arg1 O-GlcNAcylation 165:179 INTRODUCTION O-GlcNAcylation 152:179 INTRODUCTION O-GlcNAcylation 152:179 INTRODUCTION O-GlcNAcylation is an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety linked to the side chain hydroxyl of a serine or threonine residue. 26724145 2 37 theme epithelial 420:429 arg1 MET 443:445 MET 443:445 MET 443:445 The E-cadherin/β-catenin system, an integral component of epithelial to mesenchymal transition (EMT)/mesenchymal to epithelial transition (MET), is affected through O-GlcNAcylation. 26724145 2 37 theme epithelial 420:429 arg1 transition 431:440 epithelial transition 420:440 epithelial transition (MET) 420:446 The E-cadherin/β-catenin system, an integral component of epithelial to mesenchymal transition (EMT)/mesenchymal to epithelial transition (MET), is affected through O-GlcNAcylation. 26724145 5 38 theme invasive 1118:1125 arg1 front 1127:1131 the invasive front 1114:1131 the invasive front 1114:1131 Western blot was also conducted in primary CRC tissue RESULTS Membranous E-cadherin expression was lowest in the invasive front, but showed greater increases in metastatic nodal lesions. 26724145 2 39 theme /mesenchymal 404:415 arg1 transition 388:397 epithelial to mesenchymal transition 362:397 epithelial to mesenchymal transition (EMT)/mesenchymal to epithelial transition (MET) 362:446 The E-cadherin/β-catenin system, an integral component of epithelial to mesenchymal transition (EMT)/mesenchymal to epithelial transition (MET), is affected through O-GlcNAcylation. 26724145 2 39 theme /mesenchymal 404:415 arg1 EMT 400:402 EMT 400:402 EMT 400:402 The E-cadherin/β-catenin system, an integral component of epithelial to mesenchymal transition (EMT)/mesenchymal to epithelial transition (MET), is affected through O-GlcNAcylation. 26724145 0 40 theme Differential 0:11 arg1 expression 35:44 Differential membranous E-cadherin expression 0:44 Differential membranous E-cadherin expression 0:44 Differential membranous E-cadherin expression, cell proliferation and O-GlcNAcylation between primary and metastatic nodal lesion in colorectal cancer. 26724145 1 41 theme residue 295:301 arg1 hydroxyl 261:268 the side chain hydroxyl 246:268 the side chain hydroxyl of a serine or threonine residue 246:301 INTRODUCTION O-GlcNAcylation is an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety linked to the side chain hydroxyl of a serine or threonine residue. 26724145 9 42 theme invasive 1592:1599 arg1 front 1601:1605 the invasive front 1588:1605 the invasive front 1588:1605 O-GlcNAcylation expression decreased in metastatic nodal lesions compared to the invasive front and tumor center, and was inversely correlated with Ki67 LI. 26724145 0 43 theme E-cadherin 24:33 arg1 expression 35:44 Differential membranous E-cadherin expression 0:44 Differential membranous E-cadherin expression 0:44 Differential membranous E-cadherin expression, cell proliferation and O-GlcNAcylation between primary and metastatic nodal lesion in colorectal cancer. 26724145 10 44 theme invasive 1755:1762 arg1 front 1764:1768 invasive front 1755:1768 invasive front 1755:1768 However, O-GlcNAcylation expression was only slightly changed between tumor center and invasive front. 26724145 10 45 theme O-GlcNAcylation 1677:1691 arg1 expression 1693:1702 O-GlcNAcylation expression 1677:1702 O-GlcNAcylation expression 1677:1702 However, O-GlcNAcylation expression was only slightly changed between tumor center and invasive front. 26724145 3 46 theme lesions 642:648 arg1 center 553:558 the tumor center 543:558 the tumor center 543:558 The current study examined the status of EMT/MET in both the tumor center and invasive front of the primary colorectal carcinoma (CRC) and metastatic nodal lesions, which were compared to O-GlcNAcylation expression levels in those areas. 26724145 3 46 theme lesions 642:648 arg1 front 573:577 invasive front 564:577 invasive front 564:577 The current study examined the status of EMT/MET in both the tumor center and invasive front of the primary colorectal carcinoma (CRC) and metastatic nodal lesions, which were compared to O-GlcNAcylation expression levels in those areas. 26724145 8 47 theme Primary 1397:1403 arg1 CRC 1405:1407 Primary CRC 1397:1407 Primary CRC 1397:1407 Primary CRC showed higher expression of O-GlcNAcylation and O-GlcNAc-transferase (OGT) than nonneoplastic colons. 26724145 5 48 theme metastatic 1166:1175 arg1 lesions 1183:1189 metastatic nodal lesions 1166:1189 metastatic nodal lesions 1166:1189 Western blot was also conducted in primary CRC tissue RESULTS Membranous E-cadherin expression was lowest in the invasive front, but showed greater increases in metastatic nodal lesions. 26724145 5 49 theme primary 1040:1046 arg1 RESULTS 1059:1065 primary CRC tissue RESULTS 1040:1065 primary CRC tissue RESULTS Membranous E-cadherin expression was lowest in the invasive front, but showed greater increases in metastatic nodal lesions 1040:1189 Western blot was also conducted in primary CRC tissue RESULTS Membranous E-cadherin expression was lowest in the invasive front, but showed greater increases in metastatic nodal lesions. 26724145 7 50 theme Ki67 1295:1298 arg1 LI 1316:1317 LI 1316:1317 LI 1316:1317 The Ki67 labeling index (LI) was lowest in the invasive front, and increased in metastatic nodal lesions. 26724145 7 50 theme Ki67 1295:1298 arg1 lowest 1324:1329 lowest 1324:1329 lowest 1324:1329 The Ki67 labeling index (LI) was lowest in the invasive front, and increased in metastatic nodal lesions. 26724145 7 50 theme Ki67 1295:1298 arg1 index 1309:1313 The Ki67 labeling index 1291:1313 The Ki67 labeling index (LI) 1291:1318 The Ki67 labeling index (LI) was lowest in the invasive front, and increased in metastatic nodal lesions. 26724145 3 51 theme O-GlcNAcylation 674:688 arg1 levels 701:706 O-GlcNAcylation expression levels 674:706 O-GlcNAcylation expression levels in those areas 674:721 The current study examined the status of EMT/MET in both the tumor center and invasive front of the primary colorectal carcinoma (CRC) and metastatic nodal lesions, which were compared to O-GlcNAcylation expression levels in those areas. 26724145 13 52 theme metastatic 2108:2117 arg1 lesion 2125:2130 metastatic nodal lesion 2108:2130 metastatic nodal lesion compared to primary CRC 2108:2154 CONCLUSIONS Differential membranous E-cadherin expression, cell proliferation and O-GlcNAcylation in metastatic nodal lesion compared to primary CRC may play role in establishing its lesions; however, these findings are not sufficient to show the role of O-GlcNAcylation in the EMT/MET of CRC. 26724145 11 53 theme nuclear 1849:1855 arg1 β-catenin 1857:1865 nuclear β-catenin 1849:1865 nuclear β-catenin 1849:1865 In addition, there was no correlation between its expression and the level of nuclear β-catenin, membranous E-cadherin and Snail. 26724145 1 54 theme side 250:253 arg1 chain 255:259 the side chain 246:259 the side chain hydroxyl of a serine or threonine residue 246:301 INTRODUCTION O-GlcNAcylation is an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety linked to the side chain hydroxyl of a serine or threonine residue. 26724145 5 55 theme Western 1005:1011 arg1 blot 1013:1016 Western blot 1005:1016 Western blot 1005:1016 Western blot was also conducted in primary CRC tissue RESULTS Membranous E-cadherin expression was lowest in the invasive front, but showed greater increases in metastatic nodal lesions. 26724145 4 56 theme Immunohistochemical 825:843 arg1 staining 845:852 Immunohistochemical staining 825:852 Immunohistochemical staining for E-cadherin, β-catenin, Snail, O-GlcNAc and Ki67 825:904 In addition, the cliniopathological significance of O-GlcNAcylation was studied MATERIAL AND METHODS Immunohistochemical staining for E-cadherin, β-catenin, Snail, O-GlcNAc and Ki67 was performed in 40 primary CRC tissues, 40 nonneoplastic colons, and 17 nodal metastatic lesions. 26724145 11 57 theme Snail 1894:1898 arg1 expression 1821:1830 its expression 1817:1830 its expression 1817:1830 In addition, there was no correlation between its expression and the level of nuclear β-catenin, membranous E-cadherin and Snail. 26724145 11 57 theme Snail 1894:1898 arg1 level 1840:1844 the level 1836:1844 the level of nuclear β-catenin, membranous E-cadherin and Snail 1836:1898 In addition, there was no correlation between its expression and the level of nuclear β-catenin, membranous E-cadherin and Snail. 26724145 2 58 theme transition 388:397 arg1 component 349:357 an integral component 337:357 an integral component of epithelial to mesenchymal transition (EMT)/mesenchymal to epithelial transition (MET) 337:446 The E-cadherin/β-catenin system, an integral component of epithelial to mesenchymal transition (EMT)/mesenchymal to epithelial transition (MET), is affected through O-GlcNAcylation. 26724145 2 58 theme transition 388:397 arg1 system 329:334 The E-cadherin/β-catenin system 304:334 The E-cadherin/β-catenin system 304:334 The E-cadherin/β-catenin system, an integral component of epithelial to mesenchymal transition (EMT)/mesenchymal to epithelial transition (MET), is affected through O-GlcNAcylation. 26724145 5 59 from increases 1153:1161 arg1 lesions 1183:1189 metastatic nodal lesions 1166:1189 metastatic nodal lesions 1166:1189 Western blot was also conducted in primary CRC tissue RESULTS Membranous E-cadherin expression was lowest in the invasive front, but showed greater increases in metastatic nodal lesions. 26724145 13 60 theme Differential 2019:2030 arg1 expression 2054:2063 Differential membranous E-cadherin expression 2019:2063 Differential membranous E-cadherin expression 2019:2063 CONCLUSIONS Differential membranous E-cadherin expression, cell proliferation and O-GlcNAcylation in metastatic nodal lesion compared to primary CRC may play role in establishing its lesions; however, these findings are not sufficient to show the role of O-GlcNAcylation in the EMT/MET of CRC. 26724145 2 61 theme E-cadherin/β-catenin 308:327 arg1 component 349:357 an integral component 337:357 an integral component of epithelial to mesenchymal transition (EMT)/mesenchymal to epithelial transition (MET) 337:446 The E-cadherin/β-catenin system, an integral component of epithelial to mesenchymal transition (EMT)/mesenchymal to epithelial transition (MET), is affected through O-GlcNAcylation. 26724145 2 61 theme E-cadherin/β-catenin 308:327 arg1 system 329:334 The E-cadherin/β-catenin system 304:334 The E-cadherin/β-catenin system 304:334 The E-cadherin/β-catenin system, an integral component of epithelial to mesenchymal transition (EMT)/mesenchymal to epithelial transition (MET), is affected through O-GlcNAcylation. 26724145 13 62 theme E-cadherin 2043:2052 arg1 expression 2054:2063 Differential membranous E-cadherin expression 2019:2063 Differential membranous E-cadherin expression 2019:2063 CONCLUSIONS Differential membranous E-cadherin expression, cell proliferation and O-GlcNAcylation in metastatic nodal lesion compared to primary CRC may play role in establishing its lesions; however, these findings are not sufficient to show the role of O-GlcNAcylation in the EMT/MET of CRC. 26724145 13 63 from expression 2054:2063 arg1 lesion 2125:2130 metastatic nodal lesion 2108:2130 metastatic nodal lesion compared to primary CRC 2108:2154 CONCLUSIONS Differential membranous E-cadherin expression, cell proliferation and O-GlcNAcylation in metastatic nodal lesion compared to primary CRC may play role in establishing its lesions; however, these findings are not sufficient to show the role of O-GlcNAcylation in the EMT/MET of CRC. 26724145 1 64 theme β-N-acetylglucosamine 196:216 arg1 O-GlcNAcylation 165:179 INTRODUCTION O-GlcNAcylation 152:179 INTRODUCTION O-GlcNAcylation 152:179 INTRODUCTION O-GlcNAcylation is an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety linked to the side chain hydroxyl of a serine or threonine residue. 26724145 1 64 theme β-N-acetylglucosamine 196:216 arg1 moiety 229:234 an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety 184:234 an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety linked to the side chain hydroxyl of a serine or threonine residue 184:301 INTRODUCTION O-GlcNAcylation is an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety linked to the side chain hydroxyl of a serine or threonine residue. 26724145 13 65 theme O-GlcNAcylation 2262:2276 arg1 role 2254:2257 the role 2250:2257 the role of O-GlcNAcylation in the EMT/MET of CRC 2250:2298 CONCLUSIONS Differential membranous E-cadherin expression, cell proliferation and O-GlcNAcylation in metastatic nodal lesion compared to primary CRC may play role in establishing its lesions; however, these findings are not sufficient to show the role of O-GlcNAcylation in the EMT/MET of CRC. 26724145 6 66 theme nuclear 1262:1268 arg1 β-catenin 1270:1278 nuclear β-catenin 1262:1278 nuclear β-catenin 1262:1278 Moreover, its expression level was negatively correlated with that of nuclear β-catenin and Snail. 26724145 2 67 theme integral 340:347 arg1 component 349:357 an integral component 337:357 an integral component of epithelial to mesenchymal transition (EMT)/mesenchymal to epithelial transition (MET) 337:446 The E-cadherin/β-catenin system, an integral component of epithelial to mesenchymal transition (EMT)/mesenchymal to epithelial transition (MET), is affected through O-GlcNAcylation. 26724145 2 67 theme integral 340:347 arg1 system 329:334 The E-cadherin/β-catenin system 304:334 The E-cadherin/β-catenin system 304:334 The E-cadherin/β-catenin system, an integral component of epithelial to mesenchymal transition (EMT)/mesenchymal to epithelial transition (MET), is affected through O-GlcNAcylation. 26724145 1 68 theme O-GlcNAc 219:226 arg1 O-GlcNAcylation 165:179 INTRODUCTION O-GlcNAcylation 152:179 INTRODUCTION O-GlcNAcylation 152:179 INTRODUCTION O-GlcNAcylation is an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety linked to the side chain hydroxyl of a serine or threonine residue. 26724145 1 68 theme O-GlcNAc 219:226 arg1 moiety 229:234 an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety 184:234 an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety linked to the side chain hydroxyl of a serine or threonine residue 184:301 INTRODUCTION O-GlcNAcylation is an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety linked to the side chain hydroxyl of a serine or threonine residue. 26724145 3 69 from status 517:522 arg1 center 553:558 the tumor center 543:558 the tumor center 543:558 The current study examined the status of EMT/MET in both the tumor center and invasive front of the primary colorectal carcinoma (CRC) and metastatic nodal lesions, which were compared to O-GlcNAcylation expression levels in those areas. 26724145 3 69 from status 517:522 arg1 front 573:577 invasive front 564:577 invasive front 564:577 The current study examined the status of EMT/MET in both the tumor center and invasive front of the primary colorectal carcinoma (CRC) and metastatic nodal lesions, which were compared to O-GlcNAcylation expression levels in those areas. 26724145 3 70 theme invasive 564:571 arg1 front 573:577 invasive front 564:577 invasive front 564:577 The current study examined the status of EMT/MET in both the tumor center and invasive front of the primary colorectal carcinoma (CRC) and metastatic nodal lesions, which were compared to O-GlcNAcylation expression levels in those areas. 26724145 4 71 theme CRC 934:936 arg1 tissues 938:944 40 primary CRC tissues 923:944 40 primary CRC tissues 923:944 In addition, the cliniopathological significance of O-GlcNAcylation was studied MATERIAL AND METHODS Immunohistochemical staining for E-cadherin, β-catenin, Snail, O-GlcNAc and Ki67 was performed in 40 primary CRC tissues, 40 nonneoplastic colons, and 17 nodal metastatic lesions. 26724145 8 72 theme O-GlcNAcylation 1437:1451 arg1 expression 1423:1432 higher expression 1416:1432 higher expression of O-GlcNAcylation and O-GlcNAc-transferase (OGT) 1416:1482 Primary CRC showed higher expression of O-GlcNAcylation and O-GlcNAc-transferase (OGT) than nonneoplastic colons. 26724145 9 73 theme metastatic 1551:1560 arg1 lesions 1568:1574 metastatic nodal lesions 1551:1574 metastatic nodal lesions 1551:1574 O-GlcNAcylation expression decreased in metastatic nodal lesions compared to the invasive front and tumor center, and was inversely correlated with Ki67 LI. 26724145 3 74 theme carcinoma 605:613 arg1 center 553:558 the tumor center 543:558 the tumor center 543:558 The current study examined the status of EMT/MET in both the tumor center and invasive front of the primary colorectal carcinoma (CRC) and metastatic nodal lesions, which were compared to O-GlcNAcylation expression levels in those areas. 26724145 3 74 theme carcinoma 605:613 arg1 front 573:577 invasive front 564:577 invasive front 564:577 The current study examined the status of EMT/MET in both the tumor center and invasive front of the primary colorectal carcinoma (CRC) and metastatic nodal lesions, which were compared to O-GlcNAcylation expression levels in those areas. 26724145 8 75 theme O-GlcNAc-transferase 1457:1476 arg1 expression 1423:1432 higher expression 1416:1432 higher expression of O-GlcNAcylation and O-GlcNAc-transferase (OGT) 1416:1482 Primary CRC showed higher expression of O-GlcNAcylation and O-GlcNAc-transferase (OGT) than nonneoplastic colons. 26724145 7 76 theme metastatic 1371:1380 arg1 lesions 1388:1394 metastatic nodal lesions 1371:1394 metastatic nodal lesions 1371:1394 The Ki67 labeling index (LI) was lowest in the invasive front, and increased in metastatic nodal lesions. 26724145 3 77 theme primary 586:592 arg1 carcinoma 605:613 the primary colorectal carcinoma 582:613 the primary colorectal carcinoma (CRC) 582:619 The current study examined the status of EMT/MET in both the tumor center and invasive front of the primary colorectal carcinoma (CRC) and metastatic nodal lesions, which were compared to O-GlcNAcylation expression levels in those areas. 26724145 3 77 theme primary 586:592 arg1 CRC 616:618 CRC 616:618 CRC 616:618 The current study examined the status of EMT/MET in both the tumor center and invasive front of the primary colorectal carcinoma (CRC) and metastatic nodal lesions, which were compared to O-GlcNAcylation expression levels in those areas. 26724145 13 78 from role 2254:2257 arg1 EMT/MET 2285:2291 the EMT/MET 2281:2291 the EMT/MET of CRC 2281:2298 CONCLUSIONS Differential membranous E-cadherin expression, cell proliferation and O-GlcNAcylation in metastatic nodal lesion compared to primary CRC may play role in establishing its lesions; however, these findings are not sufficient to show the role of O-GlcNAcylation in the EMT/MET of CRC. 26724145 5 79 theme tissue 1052:1057 arg1 RESULTS 1059:1065 primary CRC tissue RESULTS 1040:1065 primary CRC tissue RESULTS Membranous E-cadherin expression was lowest in the invasive front, but showed greater increases in metastatic nodal lesions 1040:1189 Western blot was also conducted in primary CRC tissue RESULTS Membranous E-cadherin expression was lowest in the invasive front, but showed greater increases in metastatic nodal lesions. 26724145 5 80 theme Membranous 1067:1076 arg1 expression 1089:1098 Membranous E-cadherin expression 1067:1098 Membranous E-cadherin expression 1067:1098 Western blot was also conducted in primary CRC tissue RESULTS Membranous E-cadherin expression was lowest in the invasive front, but showed greater increases in metastatic nodal lesions. 26724145 7 81 theme invasive 1338:1345 arg1 front 1347:1351 the invasive front 1334:1351 the invasive front 1334:1351 The Ki67 labeling index (LI) was lowest in the invasive front, and increased in metastatic nodal lesions. 26724145 4 82 theme metastatic 985:994 arg1 lesions 996:1002 17 nodal metastatic lesions 976:1002 17 nodal metastatic lesions 976:1002 In addition, the cliniopathological significance of O-GlcNAcylation was studied MATERIAL AND METHODS Immunohistochemical staining for E-cadherin, β-catenin, Snail, O-GlcNAc and Ki67 was performed in 40 primary CRC tissues, 40 nonneoplastic colons, and 17 nodal metastatic lesions. 26724145 0 83 theme nodal 117:121 arg1 lesion 123:128 primary and metastatic nodal lesion 94:128 primary and metastatic nodal lesion in colorectal cancer 94:149 Differential membranous E-cadherin expression, cell proliferation and O-GlcNAcylation between primary and metastatic nodal lesion in colorectal cancer. 26724145 5 84 theme greater 1145:1151 arg1 increases 1153:1161 greater increases 1145:1161 greater increases in metastatic nodal lesions 1145:1189 Western blot was also conducted in primary CRC tissue RESULTS Membranous E-cadherin expression was lowest in the invasive front, but showed greater increases in metastatic nodal lesions. 26724145 9 85 theme nodal 1562:1566 arg1 lesions 1568:1574 metastatic nodal lesions 1551:1574 metastatic nodal lesions 1551:1574 O-GlcNAcylation expression decreased in metastatic nodal lesions compared to the invasive front and tumor center, and was inversely correlated with Ki67 LI. 26724145 4 86 theme nonneoplastic 950:962 arg1 colons 964:969 40 nonneoplastic colons 947:969 40 nonneoplastic colons 947:969 In addition, the cliniopathological significance of O-GlcNAcylation was studied MATERIAL AND METHODS Immunohistochemical staining for E-cadherin, β-catenin, Snail, O-GlcNAc and Ki67 was performed in 40 primary CRC tissues, 40 nonneoplastic colons, and 17 nodal metastatic lesions. 26724145 2 87 dep mesenchymal 376:386 arg1 to 373:374 to 373:374 to 373:374 The E-cadherin/β-catenin system, an integral component of epithelial to mesenchymal transition (EMT)/mesenchymal to epithelial transition (MET), is affected through O-GlcNAcylation. 26724145 12 88 theme significant 1904:1914 arg1 relationship 1916:1927 No significant relationship 1901:1927 No significant relationship 1901:1927 No significant relationship was observed between O-GlcNAcylation level and cliniopathological parameters. 26724145 0 89 theme membranous 13:22 arg1 expression 35:44 Differential membranous E-cadherin expression 0:44 Differential membranous E-cadherin expression 0:44 Differential membranous E-cadherin expression, cell proliferation and O-GlcNAcylation between primary and metastatic nodal lesion in colorectal cancer. 26724145 1 90 link O-linked 187:194 arg1 O-GlcNAcylation 165:179 INTRODUCTION O-GlcNAcylation 152:179 INTRODUCTION O-GlcNAcylation 152:179 INTRODUCTION O-GlcNAcylation is an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety linked to the side chain hydroxyl of a serine or threonine residue. 26724145 1 90 link O-linked 187:194 arg1 moiety 229:234 an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety 184:234 an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety linked to the side chain hydroxyl of a serine or threonine residue 184:301 INTRODUCTION O-GlcNAcylation is an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety linked to the side chain hydroxyl of a serine or threonine residue. 26724145 4 91 theme cliniopathological 741:758 arg1 significance 760:771 the cliniopathological significance 737:771 the cliniopathological significance of O-GlcNAcylation 737:790 In addition, the cliniopathological significance of O-GlcNAcylation was studied MATERIAL AND METHODS Immunohistochemical staining for E-cadherin, β-catenin, Snail, O-GlcNAc and Ki67 was performed in 40 primary CRC tissues, 40 nonneoplastic colons, and 17 nodal metastatic lesions. 26724145 3 92 theme current 490:496 arg1 study 498:502 The current study 486:502 The current study 486:502 The current study examined the status of EMT/MET in both the tumor center and invasive front of the primary colorectal carcinoma (CRC) and metastatic nodal lesions, which were compared to O-GlcNAcylation expression levels in those areas. 26724145 0 93 theme cell 47:50 arg1 proliferation 52:64 cell proliferation 47:64 cell proliferation 47:64 Differential membranous E-cadherin expression, cell proliferation and O-GlcNAcylation between primary and metastatic nodal lesion in colorectal cancer. 26724145 13 94 theme CRC 2296:2298 arg1 EMT/MET 2285:2291 the EMT/MET 2281:2291 the EMT/MET of CRC 2281:2298 CONCLUSIONS Differential membranous E-cadherin expression, cell proliferation and O-GlcNAcylation in metastatic nodal lesion compared to primary CRC may play role in establishing its lesions; however, these findings are not sufficient to show the role of O-GlcNAcylation in the EMT/MET of CRC. 26724145 9 95 theme tumor 1611:1615 arg1 center 1617:1622 tumor center 1611:1622 tumor center 1611:1622 O-GlcNAcylation expression decreased in metastatic nodal lesions compared to the invasive front and tumor center, and was inversely correlated with Ki67 LI. 26724145 7 96 theme labeling 1300:1307 arg1 LI 1316:1317 LI 1316:1317 LI 1316:1317 The Ki67 labeling index (LI) was lowest in the invasive front, and increased in metastatic nodal lesions. 26724145 7 96 theme labeling 1300:1307 arg1 lowest 1324:1329 lowest 1324:1329 lowest 1324:1329 The Ki67 labeling index (LI) was lowest in the invasive front, and increased in metastatic nodal lesions. 26724145 7 96 theme labeling 1300:1307 arg1 index 1309:1313 The Ki67 labeling index 1291:1313 The Ki67 labeling index (LI) 1291:1318 The Ki67 labeling index (LI) was lowest in the invasive front, and increased in metastatic nodal lesions. 26724145 3 97 theme nodal 636:640 arg1 lesions 642:648 metastatic nodal lesions 625:648 metastatic nodal lesions 625:648 The current study examined the status of EMT/MET in both the tumor center and invasive front of the primary colorectal carcinoma (CRC) and metastatic nodal lesions, which were compared to O-GlcNAcylation expression levels in those areas. 26724145 1 98 attach linked 236:241 arg1 hydroxyl 261:268 the side chain hydroxyl 246:268 the side chain hydroxyl of a serine or threonine residue 246:301 INTRODUCTION O-GlcNAcylation is an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety linked to the side chain hydroxyl of a serine or threonine residue. 26724145 1 98 attach linked 236:241 arg2 moiety 229:234 an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety 184:234 an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety linked to the side chain hydroxyl of a serine or threonine residue 184:301 INTRODUCTION O-GlcNAcylation is an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety linked to the side chain hydroxyl of a serine or threonine residue. 26724145 1 98 attach linked 236:241 arg2 O-GlcNAcylation 165:179 INTRODUCTION O-GlcNAcylation 152:179 INTRODUCTION O-GlcNAcylation 152:179 INTRODUCTION O-GlcNAcylation is an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety linked to the side chain hydroxyl of a serine or threonine residue. 26724145 11 99 theme membranous 1868:1877 arg1 E-cadherin 1879:1888 membranous E-cadherin 1868:1888 membranous E-cadherin 1868:1888 In addition, there was no correlation between its expression and the level of nuclear β-catenin, membranous E-cadherin and Snail. 26724145 5 100 theme nodal 1177:1181 arg1 lesions 1183:1189 metastatic nodal lesions 1166:1189 metastatic nodal lesions 1166:1189 Western blot was also conducted in primary CRC tissue RESULTS Membranous E-cadherin expression was lowest in the invasive front, but showed greater increases in metastatic nodal lesions. 26724145 11 101 theme β-catenin 1857:1865 arg1 expression 1821:1830 its expression 1817:1830 its expression 1817:1830 In addition, there was no correlation between its expression and the level of nuclear β-catenin, membranous E-cadherin and Snail. 26724145 11 101 theme β-catenin 1857:1865 arg1 level 1840:1844 the level 1836:1844 the level of nuclear β-catenin, membranous E-cadherin and Snail 1836:1898 In addition, there was no correlation between its expression and the level of nuclear β-catenin, membranous E-cadherin and Snail. 26724145 1 102 theme chain 255:259 arg1 hydroxyl 261:268 the side chain hydroxyl 246:268 the side chain hydroxyl of a serine or threonine residue 246:301 INTRODUCTION O-GlcNAcylation is an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety linked to the side chain hydroxyl of a serine or threonine residue. 26724145 8 103 theme higher 1416:1421 arg1 expression 1423:1432 higher expression 1416:1432 higher expression of O-GlcNAcylation and O-GlcNAc-transferase (OGT) 1416:1482 Primary CRC showed higher expression of O-GlcNAcylation and O-GlcNAc-transferase (OGT) than nonneoplastic colons. 26724145 13 104 theme cell 2066:2069 arg1 proliferation 2071:2083 cell proliferation 2066:2083 cell proliferation 2066:2083 CONCLUSIONS Differential membranous E-cadherin expression, cell proliferation and O-GlcNAcylation in metastatic nodal lesion compared to primary CRC may play role in establishing its lesions; however, these findings are not sufficient to show the role of O-GlcNAcylation in the EMT/MET of CRC. 25568075 12 0 theme new 1826:1828 arg1 evidence 1830:1837 new evidence 1826:1837 new evidence of leptin-induced stimulation of the HBP 1826:1878 These data demonstrate development of leptin resistance in sucrose-drinking mice and provide new evidence of leptin-induced stimulation of the HBP. 25568075 7 1 from effect 1174:1179 arg1 cells 1217:1221 leptin responsiveness cells 1195:1221 leptin responsiveness cells 1195:1221 To test the effect of glucose on leptin responsiveness cells were incubated in 5.5 mM (LG) or 20 mM (HG) glucose for 18 h and were treated with 0 or 50 ng/ml leptin for 15 min. 25568075 4 2 theme signaling 819:827 arg1 suppressor 796:805 suppressor 796:805 suppressor of cytokine signaling 3 in the liver and hypothalamus 796:859 Resistance was associated with increased activity of the HBP and with phosphorylation of transcription factor signal transducer and activator of transcription-3 Tyr705 [pSTAT3(Y705)] but inhibition of suppressor of cytokine signaling 3 in the liver and hypothalamus. 25568075 2 3 theme leptin 374:379 arg1 responsiveness 381:394 leptin responsiveness 374:394 leptin responsiveness in mice in which HBP activity was stimulated by offering 30% sucrose solution in addition to chow and water or by infusing glucosamine 374:529 Here we tested leptin responsiveness in mice in which HBP activity was stimulated by offering 30% sucrose solution in addition to chow and water or by infusing glucosamine. 25568075 1 4 theme 2-day 179:183 arg1 infusion 196:203 a 2-day peripheral infusion 177:203 a 2-day peripheral infusion of glucosamine 177:218 We previously reported that a 2-day peripheral infusion of glucosamine caused leptin resistance in rats, suggesting a role for the hexosamine biosynthetic pathway (HBP) in the development of leptin resistance. 25568075 12 5 theme sucrose-drinking 1792:1807 arg1 mice 1809:1812 sucrose-drinking mice 1792:1812 sucrose-drinking mice 1792:1812 These data demonstrate development of leptin resistance in sucrose-drinking mice and provide new evidence of leptin-induced stimulation of the HBP. 25568075 0 6 theme leptin-dependent 109:124 arg1 phosphorylation 132:146 leptin-dependent STAT3 phosphorylation 109:146 leptin-dependent STAT3 phosphorylation 109:146 In vivo and in vitro evidence that chronic activation of the hexosamine biosynthetic pathway interferes with leptin-dependent STAT3 phosphorylation. 25568075 1 7 theme glucosamine 208:218 arg1 infusion 196:203 a 2-day peripheral infusion 177:203 a 2-day peripheral infusion of glucosamine 177:218 We previously reported that a 2-day peripheral infusion of glucosamine caused leptin resistance in rats, suggesting a role for the hexosamine biosynthetic pathway (HBP) in the development of leptin resistance. 25568075 1 8 theme leptin 227:232 arg1 resistance 234:243 leptin resistance 227:243 leptin resistance 227:243 We previously reported that a 2-day peripheral infusion of glucosamine caused leptin resistance in rats, suggesting a role for the hexosamine biosynthetic pathway (HBP) in the development of leptin resistance. 25568075 12 9 theme resistance 1778:1787 arg1 development 1756:1766 development 1756:1766 development of leptin resistance in sucrose-drinking mice 1756:1812 These data demonstrate development of leptin resistance in sucrose-drinking mice and provide new evidence of leptin-induced stimulation of the HBP. 25568075 9 10 theme HG 1552:1553 arg1 cells 1555:1559 HG cells 1552:1559 HG cells 1552:1559 Leptin did not stimulate these proteins in HG cells, suggesting leptin resistance. 25568075 4 11 theme transcription 684:696 arg1 factor 698:703 transcription factor signal transducer and activator of transcription-3 Tyr705 [pSTAT3(Y705)] but inhibition of suppressor of cytokine signaling 3 in the liver and hypothalamus 684:859 transcription factor signal transducer and activator of transcription-3 Tyr705 [pSTAT3(Y705)] but inhibition of suppressor of cytokine signaling 3 in the liver and hypothalamus 684:859 Resistance was associated with increased activity of the HBP and with phosphorylation of transcription factor signal transducer and activator of transcription-3 Tyr705 [pSTAT3(Y705)] but inhibition of suppressor of cytokine signaling 3 in the liver and hypothalamus. 25568075 6 12 theme HepG2 1149:1153 arg1 cells 1155:1159 HepG2 cells 1149:1159 HepG2 cells 1149:1159 In an in vitro system, glucose, glucosamine, and leptin each dose dependently increased O-linked β-N-acetylglucosamine (O-GlcNAc) protein and pSTAT3(Y705) in HepG2 cells. 25568075 4 13 theme HBP 652:654 arg1 activity 636:643 increased activity 626:643 increased activity of the HBP 626:654 Resistance was associated with increased activity of the HBP and with phosphorylation of transcription factor signal transducer and activator of transcription-3 Tyr705 [pSTAT3(Y705)] but inhibition of suppressor of cytokine signaling 3 in the liver and hypothalamus. 25568075 4 14 theme signal 705:710 arg1 transducer 712:721 signal transducer 705:721 signal transducer 705:721 Resistance was associated with increased activity of the HBP and with phosphorylation of transcription factor signal transducer and activator of transcription-3 Tyr705 [pSTAT3(Y705)] but inhibition of suppressor of cytokine signaling 3 in the liver and hypothalamus. 25568075 9 15 theme leptin 1573:1578 arg1 resistance 1580:1589 leptin resistance 1573:1589 leptin resistance 1573:1589 Leptin did not stimulate these proteins in HG cells, suggesting leptin resistance. 25568075 4 16 from hypothalamus 848:859 arg1 suppressor 796:805 suppressor 796:805 suppressor of cytokine signaling 3 in the liver and hypothalamus 796:859 Resistance was associated with increased activity of the HBP and with phosphorylation of transcription factor signal transducer and activator of transcription-3 Tyr705 [pSTAT3(Y705)] but inhibition of suppressor of cytokine signaling 3 in the liver and hypothalamus. 25568075 5 17 theme Intravenous 862:872 arg1 infusion 874:881 Intravenous infusion 862:881 Intravenous infusion of glucosamine for 3 h 862:904 Intravenous infusion of glucosamine for 3 h stimulated pSTAT3(Y705) but prevented leptin-induced phosphorylation of STAT3(S727). 25568075 4 18 from liver 838:842 arg1 suppressor 796:805 suppressor 796:805 suppressor of cytokine signaling 3 in the liver and hypothalamus 796:859 Resistance was associated with increased activity of the HBP and with phosphorylation of transcription factor signal transducer and activator of transcription-3 Tyr705 [pSTAT3(Y705)] but inhibition of suppressor of cytokine signaling 3 in the liver and hypothalamus. 25568075 4 19 theme Tyr705 756:761 arg1 Y705 771:774 Y705 771:774 Y705 771:774 Resistance was associated with increased activity of the HBP and with phosphorylation of transcription factor signal transducer and activator of transcription-3 Tyr705 [pSTAT3(Y705)] but inhibition of suppressor of cytokine signaling 3 in the liver and hypothalamus. 25568075 4 19 theme Tyr705 756:761 arg1 [pSTAT3 763:769 transcription-3 Tyr705 [pSTAT3 740:769 transcription-3 Tyr705 [pSTAT3(Y705)] 740:776 Resistance was associated with increased activity of the HBP and with phosphorylation of transcription factor signal transducer and activator of transcription-3 Tyr705 [pSTAT3(Y705)] but inhibition of suppressor of cytokine signaling 3 in the liver and hypothalamus. 25568075 0 20 theme biosynthetic 72:83 arg1 pathway 85:91 the hexosamine biosynthetic pathway 57:91 the hexosamine biosynthetic pathway 57:91 In vivo and in vitro evidence that chronic activation of the hexosamine biosynthetic pathway interferes with leptin-dependent STAT3 phosphorylation. 25568075 1 21 theme resistance 347:356 arg1 development 325:335 the development 321:335 the development of leptin resistance 321:356 We previously reported that a 2-day peripheral infusion of glucosamine caused leptin resistance in rats, suggesting a role for the hexosamine biosynthetic pathway (HBP) in the development of leptin resistance. 25568075 11 22 with Inhibition 1647:1656 arg1 azaserine 1671:1679 azaserine 1671:1679 azaserine 1671:1679 Inhibition of GFAT with azaserine prevented LG + leptin and HG stimulation of pSTAT3. 25568075 4 23 from signaling 819:827 arg1 liver 838:842 liver 838:842 liver 838:842 Resistance was associated with increased activity of the HBP and with phosphorylation of transcription factor signal transducer and activator of transcription-3 Tyr705 [pSTAT3(Y705)] but inhibition of suppressor of cytokine signaling 3 in the liver and hypothalamus. 25568075 4 23 from signaling 819:827 arg1 hypothalamus 848:859 hypothalamus 848:859 hypothalamus 848:859 Resistance was associated with increased activity of the HBP and with phosphorylation of transcription factor signal transducer and activator of transcription-3 Tyr705 [pSTAT3(Y705)] but inhibition of suppressor of cytokine signaling 3 in the liver and hypothalamus. 25568075 5 24 theme leptin-induced 944:957 arg1 phosphorylation 959:973 leptin-induced phosphorylation 944:973 leptin-induced phosphorylation of STAT3(S727) 944:988 Intravenous infusion of glucosamine for 3 h stimulated pSTAT3(Y705) but prevented leptin-induced phosphorylation of STAT3(S727). 25568075 8 25 theme similar 1373:1379 arg1 increases 1381:1389 similar increases 1373:1389 similar increases in O-GlcNAc protein, glutamine fructose-6-phosphate amidotransferase (GFAT), and pSTAT3(Y705) 1373:1483 HG alone and LG + leptin produced similar increases in O-GlcNAc protein, glutamine fructose-6-phosphate amidotransferase (GFAT), and pSTAT3(Y705) compared with LG media. 25568075 11 26 theme HG 1707:1708 arg1 stimulation 1710:1720 LG + leptin and HG stimulation 1691:1720 LG + leptin and HG stimulation of pSTAT3 1691:1730 Inhibition of GFAT with azaserine prevented LG + leptin and HG stimulation of pSTAT3. 25568075 0 27 theme In 0:1 arg1 evidence 21:28 In vivo and in vitro evidence 0:28 In vivo and in vitro evidence that chronic activation of the hexosamine biosynthetic pathway 0:91 In vivo and in vitro evidence that chronic activation of the hexosamine biosynthetic pathway interferes with leptin-dependent STAT3 phosphorylation. 25568075 2 28 dep stimulated 430:439 arg1 infusing 510:517 infusing 510:517 infusing glucosamine 510:529 Here we tested leptin responsiveness in mice in which HBP activity was stimulated by offering 30% sucrose solution in addition to chow and water or by infusing glucosamine. 25568075 2 28 dep stimulated 430:439 arg1 offering 444:451 offering 444:451 offering 30% sucrose solution in addition to chow and water 444:502 Here we tested leptin responsiveness in mice in which HBP activity was stimulated by offering 30% sucrose solution in addition to chow and water or by infusing glucosamine. 25568075 4 29 dep factor 698:703 arg1 activator 727:735 activator 727:735 activator of transcription-3 Tyr705 [pSTAT3(Y705)] but inhibition of suppressor of cytokine signaling 3 in the liver and hypothalamus 727:859 Resistance was associated with increased activity of the HBP and with phosphorylation of transcription factor signal transducer and activator of transcription-3 Tyr705 [pSTAT3(Y705)] but inhibition of suppressor of cytokine signaling 3 in the liver and hypothalamus. 25568075 4 29 dep factor 698:703 arg1 transducer 712:721 signal transducer 705:721 signal transducer 705:721 Resistance was associated with increased activity of the HBP and with phosphorylation of transcription factor signal transducer and activator of transcription-3 Tyr705 [pSTAT3(Y705)] but inhibition of suppressor of cytokine signaling 3 in the liver and hypothalamus. 25568075 2 30 theme HBP 413:415 arg1 activity 417:424 HBP activity 413:424 HBP activity 413:424 Here we tested leptin responsiveness in mice in which HBP activity was stimulated by offering 30% sucrose solution in addition to chow and water or by infusing glucosamine. 25568075 1 31 theme biosynthetic 291:302 arg1 HBP 313:315 HBP 313:315 HBP 313:315 We previously reported that a 2-day peripheral infusion of glucosamine caused leptin resistance in rats, suggesting a role for the hexosamine biosynthetic pathway (HBP) in the development of leptin resistance. 25568075 1 31 theme biosynthetic 291:302 arg1 pathway 304:310 the hexosamine biosynthetic pathway 276:310 the hexosamine biosynthetic pathway (HBP) 276:316 We previously reported that a 2-day peripheral infusion of glucosamine caused leptin resistance in rats, suggesting a role for the hexosamine biosynthetic pathway (HBP) in the development of leptin resistance. 25568075 2 32 dep chow 489:492 arg1 addition 477:484 addition 477:484 addition 477:484 Here we tested leptin responsiveness in mice in which HBP activity was stimulated by offering 30% sucrose solution in addition to chow and water or by infusing glucosamine. 25568075 2 33 theme sucrose 457:463 arg1 solution 465:472 30% sucrose solution 453:472 30% sucrose solution 453:472 Here we tested leptin responsiveness in mice in which HBP activity was stimulated by offering 30% sucrose solution in addition to chow and water or by infusing glucosamine. 25568075 2 34 theme 30 453:454 arg1 % 455:455 % 455:455 % 455:455 Here we tested leptin responsiveness in mice in which HBP activity was stimulated by offering 30% sucrose solution in addition to chow and water or by infusing glucosamine. 25568075 8 35 theme glutamine 1412:1420 arg1 GFAT 1461:1464 GFAT 1461:1464 GFAT 1461:1464 HG alone and LG + leptin produced similar increases in O-GlcNAc protein, glutamine fructose-6-phosphate amidotransferase (GFAT), and pSTAT3(Y705) compared with LG media. 25568075 8 35 theme glutamine 1412:1420 arg1 amidotransferase 1443:1458 glutamine fructose-6-phosphate amidotransferase 1412:1458 glutamine fructose-6-phosphate amidotransferase (GFAT) 1412:1465 HG alone and LG + leptin produced similar increases in O-GlcNAc protein, glutamine fructose-6-phosphate amidotransferase (GFAT), and pSTAT3(Y705) compared with LG media. 25568075 7 36 dep leptin 1320:1325 arg1 ng/ml 1314:1318 ng/ml 1314:1318 ng/ml 1314:1318 To test the effect of glucose on leptin responsiveness cells were incubated in 5.5 mM (LG) or 20 mM (HG) glucose for 18 h and were treated with 0 or 50 ng/ml leptin for 15 min. 25568075 11 37 theme GFAT 1661:1664 arg1 Inhibition 1647:1656 Inhibition 1647:1656 Inhibition of GFAT with azaserine 1647:1679 Inhibition of GFAT with azaserine prevented LG + leptin and HG stimulation of pSTAT3. 25568075 7 38 theme leptin 1195:1200 arg1 responsiveness 1202:1215 leptin responsiveness 1195:1215 leptin responsiveness cells 1195:1221 To test the effect of glucose on leptin responsiveness cells were incubated in 5.5 mM (LG) or 20 mM (HG) glucose for 18 h and were treated with 0 or 50 ng/ml leptin for 15 min. 25568075 11 39 theme leptin 1696:1701 arg1 stimulation 1710:1720 LG + leptin and HG stimulation 1691:1720 LG + leptin and HG stimulation of pSTAT3 1691:1730 Inhibition of GFAT with azaserine prevented LG + leptin and HG stimulation of pSTAT3. 25568075 8 40 theme LG 1499:1500 arg1 media 1502:1506 LG media 1499:1506 LG media 1499:1506 HG alone and LG + leptin produced similar increases in O-GlcNAc protein, glutamine fructose-6-phosphate amidotransferase (GFAT), and pSTAT3(Y705) compared with LG media. 25568075 12 41 theme leptin-induced 1842:1855 arg1 stimulation 1857:1867 leptin-induced stimulation 1842:1867 leptin-induced stimulation of the HBP 1842:1878 These data demonstrate development of leptin resistance in sucrose-drinking mice and provide new evidence of leptin-induced stimulation of the HBP. 25568075 0 42 dep In 0:1 arg1 vivo 3:6 vivo 3:6 vivo 3:6 In vivo and in vitro evidence that chronic activation of the hexosamine biosynthetic pathway interferes with leptin-dependent STAT3 phosphorylation. 25568075 4 43 dep liver 838:842 arg1 the 834:836 the 834:836 the 834:836 Resistance was associated with increased activity of the HBP and with phosphorylation of transcription factor signal transducer and activator of transcription-3 Tyr705 [pSTAT3(Y705)] but inhibition of suppressor of cytokine signaling 3 in the liver and hypothalamus. 25568075 7 44 theme glucose 1184:1190 arg1 effect 1174:1179 the effect 1170:1179 the effect of glucose on leptin responsiveness cells 1170:1221 To test the effect of glucose on leptin responsiveness cells were incubated in 5.5 mM (LG) or 20 mM (HG) glucose for 18 h and were treated with 0 or 50 ng/ml leptin for 15 min. 25568075 11 45 theme LG 1691:1692 arg1 stimulation 1710:1720 LG + leptin and HG stimulation 1691:1720 LG + leptin and HG stimulation of pSTAT3 1691:1730 Inhibition of GFAT with azaserine prevented LG + leptin and HG stimulation of pSTAT3. 25568075 10 46 theme Leptin-induced 1592:1605 arg1 S727 1614:1617 S727 1614:1617 S727 1614:1617 Leptin-induced pSTAT3(S727) was prevented by HG media. 25568075 10 46 theme Leptin-induced 1592:1605 arg1 pSTAT3 1607:1612 Leptin-induced pSTAT3 1592:1612 Leptin-induced pSTAT3(S727) 1592:1618 Leptin-induced pSTAT3(S727) was prevented by HG media. 25568075 6 47 theme O-linked 1079:1086 arg1 protein 1121:1127 O-linked β-N-acetylglucosamine (O-GlcNAc) protein 1079:1127 O-linked β-N-acetylglucosamine (O-GlcNAc) protein 1079:1127 In an in vitro system, glucose, glucosamine, and leptin each dose dependently increased O-linked β-N-acetylglucosamine (O-GlcNAc) protein and pSTAT3(Y705) in HepG2 cells. 25568075 4 48 theme cytokine 810:817 arg1 signaling 819:827 cytokine signaling 3 810:829 cytokine signaling 3 in the liver and hypothalamus 810:859 Resistance was associated with increased activity of the HBP and with phosphorylation of transcription factor signal transducer and activator of transcription-3 Tyr705 [pSTAT3(Y705)] but inhibition of suppressor of cytokine signaling 3 in the liver and hypothalamus. 25568075 4 49 theme increased 626:634 arg1 activity 636:643 increased activity 626:643 increased activity of the HBP 626:654 Resistance was associated with increased activity of the HBP and with phosphorylation of transcription factor signal transducer and activator of transcription-3 Tyr705 [pSTAT3(Y705)] but inhibition of suppressor of cytokine signaling 3 in the liver and hypothalamus. 25568075 1 50 theme peripheral 185:194 arg1 infusion 196:203 a 2-day peripheral infusion 177:203 a 2-day peripheral infusion of glucosamine 177:218 We previously reported that a 2-day peripheral infusion of glucosamine caused leptin resistance in rats, suggesting a role for the hexosamine biosynthetic pathway (HBP) in the development of leptin resistance. 25568075 6 51 theme O-GlcNAc 1111:1118 arg1 protein 1121:1127 O-linked β-N-acetylglucosamine (O-GlcNAc) protein 1079:1127 O-linked β-N-acetylglucosamine (O-GlcNAc) protein 1079:1127 In an in vitro system, glucose, glucosamine, and leptin each dose dependently increased O-linked β-N-acetylglucosamine (O-GlcNAc) protein and pSTAT3(Y705) in HepG2 cells. 25568075 0 52 theme STAT3 126:130 arg1 phosphorylation 132:146 leptin-dependent STAT3 phosphorylation 109:146 leptin-dependent STAT3 phosphorylation 109:146 In vivo and in vitro evidence that chronic activation of the hexosamine biosynthetic pathway interferes with leptin-dependent STAT3 phosphorylation. 25568075 6 53 theme β-N-acetylglucosamine 1088:1108 arg1 protein 1121:1127 O-linked β-N-acetylglucosamine (O-GlcNAc) protein 1079:1127 O-linked β-N-acetylglucosamine (O-GlcNAc) protein 1079:1127 In an in vitro system, glucose, glucosamine, and leptin each dose dependently increased O-linked β-N-acetylglucosamine (O-GlcNAc) protein and pSTAT3(Y705) in HepG2 cells. 25568075 10 54 theme HG 1637:1638 arg1 media 1640:1644 HG media 1637:1644 HG media 1637:1644 Leptin-induced pSTAT3(S727) was prevented by HG media. 25568075 4 55 from suppressor 796:805 arg1 liver 838:842 liver 838:842 liver 838:842 Resistance was associated with increased activity of the HBP and with phosphorylation of transcription factor signal transducer and activator of transcription-3 Tyr705 [pSTAT3(Y705)] but inhibition of suppressor of cytokine signaling 3 in the liver and hypothalamus. 25568075 4 55 from suppressor 796:805 arg1 hypothalamus 848:859 hypothalamus 848:859 hypothalamus 848:859 Resistance was associated with increased activity of the HBP and with phosphorylation of transcription factor signal transducer and activator of transcription-3 Tyr705 [pSTAT3(Y705)] but inhibition of suppressor of cytokine signaling 3 in the liver and hypothalamus. 25568075 5 56 theme glucosamine 886:896 arg1 infusion 874:881 Intravenous infusion 862:881 Intravenous infusion of glucosamine for 3 h 862:904 Intravenous infusion of glucosamine for 3 h stimulated pSTAT3(Y705) but prevented leptin-induced phosphorylation of STAT3(S727). 25568075 12 57 theme leptin 1771:1776 arg1 resistance 1778:1787 leptin resistance 1771:1787 leptin resistance 1771:1787 These data demonstrate development of leptin resistance in sucrose-drinking mice and provide new evidence of leptin-induced stimulation of the HBP. 25568075 1 58 from role 267:270 arg1 development 325:335 the development 321:335 the development of leptin resistance 321:356 We previously reported that a 2-day peripheral infusion of glucosamine caused leptin resistance in rats, suggesting a role for the hexosamine biosynthetic pathway (HBP) in the development of leptin resistance. 25568075 6 59 dep in 997:998 arg1 vitro 1000:1004 vitro 1000:1004 vitro 1000:1004 In an in vitro system, glucose, glucosamine, and leptin each dose dependently increased O-linked β-N-acetylglucosamine (O-GlcNAc) protein and pSTAT3(Y705) in HepG2 cells. 25568075 4 60 theme factor 698:703 arg1 phosphorylation 665:679 phosphorylation 665:679 phosphorylation of transcription factor signal transducer and activator of transcription-3 Tyr705 [pSTAT3(Y705)] but inhibition of suppressor of cytokine signaling 3 in the liver and hypothalamus 665:859 Resistance was associated with increased activity of the HBP and with phosphorylation of transcription factor signal transducer and activator of transcription-3 Tyr705 [pSTAT3(Y705)] but inhibition of suppressor of cytokine signaling 3 in the liver and hypothalamus. 25568075 3 61 theme access 576:581 arg1 days 568:571 33 days 565:571 33 days of access to sucrose 565:592 Mice were leptin resistant after 33 days of access to sucrose. 25568075 12 62 theme HBP 1876:1878 arg1 stimulation 1857:1867 leptin-induced stimulation 1842:1867 leptin-induced stimulation of the HBP 1842:1878 These data demonstrate development of leptin resistance in sucrose-drinking mice and provide new evidence of leptin-induced stimulation of the HBP. 25568075 0 63 theme hexosamine 61:70 arg1 pathway 85:91 the hexosamine biosynthetic pathway 57:91 the hexosamine biosynthetic pathway 57:91 In vivo and in vitro evidence that chronic activation of the hexosamine biosynthetic pathway interferes with leptin-dependent STAT3 phosphorylation. 25568075 0 64 theme pathway 85:91 arg1 activation 43:52 chronic activation 35:52 chronic activation of the hexosamine biosynthetic pathway 35:91 In vivo and in vitro evidence that chronic activation of the hexosamine biosynthetic pathway interferes with leptin-dependent STAT3 phosphorylation. 25568075 1 65 theme leptin 340:345 arg1 resistance 347:356 leptin resistance 340:356 leptin resistance 340:356 We previously reported that a 2-day peripheral infusion of glucosamine caused leptin resistance in rats, suggesting a role for the hexosamine biosynthetic pathway (HBP) in the development of leptin resistance. 25568075 4 66 theme transcription-3 740:754 arg1 Y705 771:774 Y705 771:774 Y705 771:774 Resistance was associated with increased activity of the HBP and with phosphorylation of transcription factor signal transducer and activator of transcription-3 Tyr705 [pSTAT3(Y705)] but inhibition of suppressor of cytokine signaling 3 in the liver and hypothalamus. 25568075 4 66 theme transcription-3 740:754 arg1 [pSTAT3 763:769 transcription-3 Tyr705 [pSTAT3 740:769 transcription-3 Tyr705 [pSTAT3(Y705)] 740:776 Resistance was associated with increased activity of the HBP and with phosphorylation of transcription factor signal transducer and activator of transcription-3 Tyr705 [pSTAT3(Y705)] but inhibition of suppressor of cytokine signaling 3 in the liver and hypothalamus. 25568075 4 67 theme [pSTAT3 763:769 arg1 activator 727:735 activator 727:735 activator of transcription-3 Tyr705 [pSTAT3(Y705)] but inhibition of suppressor of cytokine signaling 3 in the liver and hypothalamus 727:859 Resistance was associated with increased activity of the HBP and with phosphorylation of transcription factor signal transducer and activator of transcription-3 Tyr705 [pSTAT3(Y705)] but inhibition of suppressor of cytokine signaling 3 in the liver and hypothalamus. 25568075 4 67 theme [pSTAT3 763:769 arg1 transducer 712:721 signal transducer 705:721 signal transducer 705:721 Resistance was associated with increased activity of the HBP and with phosphorylation of transcription factor signal transducer and activator of transcription-3 Tyr705 [pSTAT3(Y705)] but inhibition of suppressor of cytokine signaling 3 in the liver and hypothalamus. 25568075 11 68 theme pSTAT3 1725:1730 arg1 stimulation 1710:1720 LG + leptin and HG stimulation 1691:1720 LG + leptin and HG stimulation of pSTAT3 1691:1730 Inhibition of GFAT with azaserine prevented LG + leptin and HG stimulation of pSTAT3. 25568075 8 69 theme O-GlcNAc 1394:1401 arg1 protein 1403:1409 O-GlcNAc protein 1394:1409 O-GlcNAc protein 1394:1409 HG alone and LG + leptin produced similar increases in O-GlcNAc protein, glutamine fructose-6-phosphate amidotransferase (GFAT), and pSTAT3(Y705) compared with LG media. 25568075 0 70 theme in 12:13 arg1 evidence 21:28 In vivo and in vitro evidence 0:28 In vivo and in vitro evidence that chronic activation of the hexosamine biosynthetic pathway 0:91 In vivo and in vitro evidence that chronic activation of the hexosamine biosynthetic pathway interferes with leptin-dependent STAT3 phosphorylation. 25568075 1 71 theme hexosamine 280:289 arg1 HBP 313:315 HBP 313:315 HBP 313:315 We previously reported that a 2-day peripheral infusion of glucosamine caused leptin resistance in rats, suggesting a role for the hexosamine biosynthetic pathway (HBP) in the development of leptin resistance. 25568075 1 71 theme hexosamine 280:289 arg1 pathway 304:310 the hexosamine biosynthetic pathway 276:310 the hexosamine biosynthetic pathway (HBP) 276:316 We previously reported that a 2-day peripheral infusion of glucosamine caused leptin resistance in rats, suggesting a role for the hexosamine biosynthetic pathway (HBP) in the development of leptin resistance. 25568075 8 72 from increases 1381:1389 arg1 protein 1403:1409 O-GlcNAc protein 1394:1409 O-GlcNAc protein 1394:1409 HG alone and LG + leptin produced similar increases in O-GlcNAc protein, glutamine fructose-6-phosphate amidotransferase (GFAT), and pSTAT3(Y705) compared with LG media. 25568075 8 72 from increases 1381:1389 arg1 Y705 1479:1482 Y705 1479:1482 Y705 1479:1482 HG alone and LG + leptin produced similar increases in O-GlcNAc protein, glutamine fructose-6-phosphate amidotransferase (GFAT), and pSTAT3(Y705) compared with LG media. 25568075 8 72 from increases 1381:1389 arg1 GFAT 1461:1464 GFAT 1461:1464 GFAT 1461:1464 HG alone and LG + leptin produced similar increases in O-GlcNAc protein, glutamine fructose-6-phosphate amidotransferase (GFAT), and pSTAT3(Y705) compared with LG media. 25568075 8 72 from increases 1381:1389 arg1 amidotransferase 1443:1458 glutamine fructose-6-phosphate amidotransferase 1412:1458 glutamine fructose-6-phosphate amidotransferase (GFAT) 1412:1465 HG alone and LG + leptin produced similar increases in O-GlcNAc protein, glutamine fructose-6-phosphate amidotransferase (GFAT), and pSTAT3(Y705) compared with LG media. 25568075 8 72 from increases 1381:1389 arg1 pSTAT3 1472:1477 pSTAT3 1472:1477 pSTAT3(Y705) 1472:1483 HG alone and LG + leptin produced similar increases in O-GlcNAc protein, glutamine fructose-6-phosphate amidotransferase (GFAT), and pSTAT3(Y705) compared with LG media. 25568075 7 73 dep mM 1245:1246 arg1 glucose 1267:1273 glucose 1267:1273 glucose 1267:1273 To test the effect of glucose on leptin responsiveness cells were incubated in 5.5 mM (LG) or 20 mM (HG) glucose for 18 h and were treated with 0 or 50 ng/ml leptin for 15 min. 25568075 6 74 theme in 997:998 arg1 system 1006:1011 an in vitro system 994:1011 an in vitro system 994:1011 In an in vitro system, glucose, glucosamine, and leptin each dose dependently increased O-linked β-N-acetylglucosamine (O-GlcNAc) protein and pSTAT3(Y705) in HepG2 cells. 25568075 2 75 theme % 455:455 arg1 solution 465:472 30% sucrose solution 453:472 30% sucrose solution 453:472 Here we tested leptin responsiveness in mice in which HBP activity was stimulated by offering 30% sucrose solution in addition to chow and water or by infusing glucosamine. 25568075 8 76 theme fructose-6-phosphate 1422:1441 arg1 GFAT 1461:1464 GFAT 1461:1464 GFAT 1461:1464 HG alone and LG + leptin produced similar increases in O-GlcNAc protein, glutamine fructose-6-phosphate amidotransferase (GFAT), and pSTAT3(Y705) compared with LG media. 25568075 8 76 theme fructose-6-phosphate 1422:1441 arg1 amidotransferase 1443:1458 glutamine fructose-6-phosphate amidotransferase 1412:1458 glutamine fructose-6-phosphate amidotransferase (GFAT) 1412:1465 HG alone and LG + leptin produced similar increases in O-GlcNAc protein, glutamine fructose-6-phosphate amidotransferase (GFAT), and pSTAT3(Y705) compared with LG media. 25568075 6 77 link O-linked 1079:1086 arg1 protein 1121:1127 O-linked β-N-acetylglucosamine (O-GlcNAc) protein 1079:1127 O-linked β-N-acetylglucosamine (O-GlcNAc) protein 1079:1127 In an in vitro system, glucose, glucosamine, and leptin each dose dependently increased O-linked β-N-acetylglucosamine (O-GlcNAc) protein and pSTAT3(Y705) in HepG2 cells. 25568075 4 78 theme inhibition 782:791 arg1 activator 727:735 activator 727:735 activator of transcription-3 Tyr705 [pSTAT3(Y705)] but inhibition of suppressor of cytokine signaling 3 in the liver and hypothalamus 727:859 Resistance was associated with increased activity of the HBP and with phosphorylation of transcription factor signal transducer and activator of transcription-3 Tyr705 [pSTAT3(Y705)] but inhibition of suppressor of cytokine signaling 3 in the liver and hypothalamus. 25568075 4 78 theme inhibition 782:791 arg1 transducer 712:721 signal transducer 705:721 signal transducer 705:721 Resistance was associated with increased activity of the HBP and with phosphorylation of transcription factor signal transducer and activator of transcription-3 Tyr705 [pSTAT3(Y705)] but inhibition of suppressor of cytokine signaling 3 in the liver and hypothalamus. 25568075 0 79 theme chronic 35:41 arg1 activation 43:52 chronic activation 35:52 chronic activation of the hexosamine biosynthetic pathway 35:91 In vivo and in vitro evidence that chronic activation of the hexosamine biosynthetic pathway interferes with leptin-dependent STAT3 phosphorylation. 25568075 7 80 dep ng/ml 1314:1318 arg1 50 1311:1312 50 1311:1312 50 1311:1312 To test the effect of glucose on leptin responsiveness cells were incubated in 5.5 mM (LG) or 20 mM (HG) glucose for 18 h and were treated with 0 or 50 ng/ml leptin for 15 min. 25568075 7 80 dep ng/ml 1314:1318 arg1 0 1306:1306 0 1306:1306 0 1306:1306 To test the effect of glucose on leptin responsiveness cells were incubated in 5.5 mM (LG) or 20 mM (HG) glucose for 18 h and were treated with 0 or 50 ng/ml leptin for 15 min. 25568075 7 81 theme responsiveness 1202:1215 arg1 cells 1217:1221 leptin responsiveness cells 1195:1221 leptin responsiveness cells 1195:1221 To test the effect of glucose on leptin responsiveness cells were incubated in 5.5 mM (LG) or 20 mM (HG) glucose for 18 h and were treated with 0 or 50 ng/ml leptin for 15 min. 25568075 4 82 theme suppressor 796:805 arg1 inhibition 782:791 inhibition 782:791 inhibition of suppressor of cytokine signaling 3 in the liver and hypothalamus 782:859 Resistance was associated with increased activity of the HBP and with phosphorylation of transcription factor signal transducer and activator of transcription-3 Tyr705 [pSTAT3(Y705)] but inhibition of suppressor of cytokine signaling 3 in the liver and hypothalamus. 25568075 0 83 dep in 12:13 arg1 vitro 15:19 vitro 15:19 vitro 15:19 In vivo and in vitro evidence that chronic activation of the hexosamine biosynthetic pathway interferes with leptin-dependent STAT3 phosphorylation. 25568075 2 84 from responsiveness 381:394 arg1 mice 399:402 mice 399:402 mice in which HBP activity was stimulated by offering 30% sucrose solution in addition to chow and water or by infusing glucosamine 399:529 Here we tested leptin responsiveness in mice in which HBP activity was stimulated by offering 30% sucrose solution in addition to chow and water or by infusing glucosamine. 25568075 12 85 theme stimulation 1857:1867 arg1 evidence 1830:1837 new evidence 1826:1837 new evidence of leptin-induced stimulation of the HBP 1826:1878 These data demonstrate development of leptin resistance in sucrose-drinking mice and provide new evidence of leptin-induced stimulation of the HBP. 25568075 12 86 from development 1756:1766 arg1 mice 1809:1812 sucrose-drinking mice 1792:1812 sucrose-drinking mice 1792:1812 These data demonstrate development of leptin resistance in sucrose-drinking mice and provide new evidence of leptin-induced stimulation of the HBP. 25568075 5 87 theme STAT3 978:982 arg1 phosphorylation 959:973 leptin-induced phosphorylation 944:973 leptin-induced phosphorylation of STAT3(S727) 944:988 Intravenous infusion of glucosamine for 3 h stimulated pSTAT3(Y705) but prevented leptin-induced phosphorylation of STAT3(S727). 25183011 6 0 theme reporter 909:916 arg1 plasmid 918:924 reporter plasmid 909:924 reporter plasmid 909:924 Indeed, co-transfection of the OGA-3'UTR containing reporter plasmid and miR-539 overexpression plasmid significantly reduced reporter activity. 25183011 3 1 with consistent 499:508 arg1 role 532:535 the pro-adaptive role 515:535 the pro-adaptive role of increased O-GlcNAcylation during heart failure 515:585 We recently reported reduced OGA expression in the failing heart, which is consistent with the pro-adaptive role of increased O-GlcNAcylation during heart failure; however, molecular mechanisms regulating these enzymes during heart failure remain unknown. 25183011 9 2 theme other 1458:1462 arg1 diseases 1474:1481 other metabolic diseases 1458:1481 other metabolic diseases 1458:1481 Manipulation of miR-539 may represent a novel therapeutic target in the treatment of heart failure and other metabolic diseases. 25183011 7 3 theme OGA 1185:1187 arg1 expression 1197:1206 OGA protein expression 1185:1206 OGA protein expression 1185:1206 Overexpression of miR-539 in neonatal rat cardiomyocytes significantly suppressed OGA expression and consequently increased O-GlcNAcylation; conversely, the miR-539 inhibitor rescued OGA protein expression and restored O-GlcNAcylation. 25183011 6 4 contain containing 898:907 arg2 plasmid 918:924 reporter plasmid 909:924 reporter plasmid 909:924 Indeed, co-transfection of the OGA-3'UTR containing reporter plasmid and miR-539 overexpression plasmid significantly reduced reporter activity. 25183011 6 4 contain containing 898:907 arg2 plasmid 953:959 miR-539 overexpression plasmid 930:959 miR-539 overexpression plasmid 930:959 Indeed, co-transfection of the OGA-3'UTR containing reporter plasmid and miR-539 overexpression plasmid significantly reduced reporter activity. 25183011 6 4 contain containing 898:907 arg1 UTR 894:896 the OGA-3'UTR 884:896 the OGA-3'UTR containing reporter plasmid and miR-539 overexpression plasmid 884:959 Indeed, co-transfection of the OGA-3'UTR containing reporter plasmid and miR-539 overexpression plasmid significantly reduced reporter activity. 25183011 6 5 theme UTR 894:896 arg1 co-transfection 865:879 co-transfection 865:879 co-transfection of the OGA-3'UTR containing reporter plasmid and miR-539 overexpression plasmid 865:959 Indeed, co-transfection of the OGA-3'UTR containing reporter plasmid and miR-539 overexpression plasmid significantly reduced reporter activity. 25183011 7 6 theme miR-539 1159:1165 arg1 inhibitor 1167:1175 the miR-539 inhibitor 1155:1175 the miR-539 inhibitor 1155:1175 Overexpression of miR-539 in neonatal rat cardiomyocytes significantly suppressed OGA expression and consequently increased O-GlcNAcylation; conversely, the miR-539 inhibitor rescued OGA protein expression and restored O-GlcNAcylation. 25183011 3 7 theme increased 540:548 arg1 O-GlcNAcylation 550:564 increased O-GlcNAcylation 540:564 increased O-GlcNAcylation during heart failure 540:585 We recently reported reduced OGA expression in the failing heart, which is consistent with the pro-adaptive role of increased O-GlcNAcylation during heart failure; however, molecular mechanisms regulating these enzymes during heart failure remain unknown. 25183011 3 8 theme heart 573:577 arg1 failure 579:585 heart failure 573:585 heart failure 573:585 We recently reported reduced OGA expression in the failing heart, which is consistent with the pro-adaptive role of increased O-GlcNAcylation during heart failure; however, molecular mechanisms regulating these enzymes during heart failure remain unknown. 25183011 9 9 theme diseases 1474:1481 arg1 treatment 1427:1435 the treatment 1423:1435 the treatment of heart failure and other metabolic diseases 1423:1481 Manipulation of miR-539 may represent a novel therapeutic target in the treatment of heart failure and other metabolic diseases. 25183011 4 10 theme miRNAs 776:781 arg1 expression 754:763 expression 754:763 expression of several miRNAs 754:781 Using miRNA microarray analysis, we observed acute and chronic changes in expression of several miRNAs. 25183011 3 11 theme O-GlcNAcylation 550:564 arg1 role 532:535 the pro-adaptive role 515:535 the pro-adaptive role of increased O-GlcNAcylation during heart failure 515:585 We recently reported reduced OGA expression in the failing heart, which is consistent with the pro-adaptive role of increased O-GlcNAcylation during heart failure; however, molecular mechanisms regulating these enzymes during heart failure remain unknown. 25183011 4 12 theme chronic 735:741 arg1 changes 743:749 acute and chronic changes 725:749 acute and chronic changes 725:749 Using miRNA microarray analysis, we observed acute and chronic changes in expression of several miRNAs. 25183011 8 13 from target 1284:1289 arg1 heart 1309:1313 the heart 1305:1313 the heart 1305:1313 In conclusion, this work identifies the first target of miR-539 in the heart and the first miRNA that regulates OGA. 25183011 3 14 theme failing 475:481 arg1 heart 483:487 the failing heart 471:487 the failing heart 471:487 We recently reported reduced OGA expression in the failing heart, which is consistent with the pro-adaptive role of increased O-GlcNAcylation during heart failure; however, molecular mechanisms regulating these enzymes during heart failure remain unknown. 25183011 4 15 theme microarray 692:701 arg1 analysis 703:710 miRNA microarray analysis 686:710 miRNA microarray analysis 686:710 Using miRNA microarray analysis, we observed acute and chronic changes in expression of several miRNAs. 25183011 3 16 theme reduced 445:451 arg1 expression 457:466 reduced OGA expression 445:466 reduced OGA expression 445:466 We recently reported reduced OGA expression in the failing heart, which is consistent with the pro-adaptive role of increased O-GlcNAcylation during heart failure; however, molecular mechanisms regulating these enzymes during heart failure remain unknown. 25183011 9 17 theme miR-539 1371:1377 arg1 Manipulation 1355:1366 Manipulation 1355:1366 Manipulation of miR-539 1355:1377 Manipulation of miR-539 may represent a novel therapeutic target in the treatment of heart failure and other metabolic diseases. 25183011 2 18 theme nuclear 390:396 arg1 proteins 414:421 many nuclear and cytoplasmic proteins 385:421 many nuclear and cytoplasmic proteins 385:421 One such signal, O-linked β-N-acetylglucosamine (O-GlcNAc), is an essential post-translational modification regulated by two enzymes, O-GlcNAc transferase and O-GlcNAcase (OGA), which modulate the function of many nuclear and cytoplasmic proteins. 25183011 9 19 dep novel 1395:1399 arg1 therapeutic 1401:1411 therapeutic 1401:1411 therapeutic 1401:1411 Manipulation of miR-539 may represent a novel therapeutic target in the treatment of heart failure and other metabolic diseases. 25183011 2 20 theme many 385:388 arg1 proteins 414:421 many nuclear and cytoplasmic proteins 385:421 many nuclear and cytoplasmic proteins 385:421 One such signal, O-linked β-N-acetylglucosamine (O-GlcNAc), is an essential post-translational modification regulated by two enzymes, O-GlcNAc transferase and O-GlcNAcase (OGA), which modulate the function of many nuclear and cytoplasmic proteins. 25183011 4 21 theme miRNA 686:690 arg1 analysis 703:710 miRNA microarray analysis 686:710 miRNA microarray analysis 686:710 Using miRNA microarray analysis, we observed acute and chronic changes in expression of several miRNAs. 25183011 6 22 theme reporter 983:990 arg1 activity 992:999 reporter activity 983:999 reporter activity 983:999 Indeed, co-transfection of the OGA-3'UTR containing reporter plasmid and miR-539 overexpression plasmid significantly reduced reporter activity. 25183011 4 23 theme several 768:774 arg1 miRNAs 776:781 several miRNAs 768:781 several miRNAs 768:781 Using miRNA microarray analysis, we observed acute and chronic changes in expression of several miRNAs. 25183011 9 24 theme novel 1395:1399 arg1 target 1413:1418 a novel therapeutic target 1393:1418 a novel therapeutic target in the treatment of heart failure and other metabolic diseases 1393:1481 Manipulation of miR-539 may represent a novel therapeutic target in the treatment of heart failure and other metabolic diseases. 25183011 2 25 theme O-GlcNAc 310:317 arg1 enzymes 301:307 two enzymes 297:307 two enzymes 297:307 One such signal, O-linked β-N-acetylglucosamine (O-GlcNAc), is an essential post-translational modification regulated by two enzymes, O-GlcNAc transferase and O-GlcNAcase (OGA), which modulate the function of many nuclear and cytoplasmic proteins. 25183011 2 25 theme O-GlcNAc 310:317 arg1 transferase 319:329 O-GlcNAc transferase 310:329 O-GlcNAc transferase 310:329 One such signal, O-linked β-N-acetylglucosamine (O-GlcNAc), is an essential post-translational modification regulated by two enzymes, O-GlcNAc transferase and O-GlcNAcase (OGA), which modulate the function of many nuclear and cytoplasmic proteins. 25183011 2 26 link O-linked 193:200 arg1 β-N-acetylglucosamine 202:222 O-linked β-N-acetylglucosamine 193:222 O-linked β-N-acetylglucosamine (O-GlcNAc) 193:233 One such signal, O-linked β-N-acetylglucosamine (O-GlcNAc), is an essential post-translational modification regulated by two enzymes, O-GlcNAc transferase and O-GlcNAcase (OGA), which modulate the function of many nuclear and cytoplasmic proteins. 25183011 2 26 link O-linked 193:200 arg1 One 176:178 One 176:178 One 176:178 One such signal, O-linked β-N-acetylglucosamine (O-GlcNAc), is an essential post-translational modification regulated by two enzymes, O-GlcNAc transferase and O-GlcNAcase (OGA), which modulate the function of many nuclear and cytoplasmic proteins. 25183011 2 26 link O-linked 193:200 arg1 O-GlcNAc 225:232 O-GlcNAc 225:232 O-GlcNAc 225:232 One such signal, O-linked β-N-acetylglucosamine (O-GlcNAc), is an essential post-translational modification regulated by two enzymes, O-GlcNAc transferase and O-GlcNAcase (OGA), which modulate the function of many nuclear and cytoplasmic proteins. 25183011 8 27 theme first 1278:1282 arg1 target 1284:1289 the first target 1274:1289 the first target of miR-539 in the heart 1274:1313 In conclusion, this work identifies the first target of miR-539 in the heart and the first miRNA that regulates OGA. 25183011 4 28 theme acute 725:729 arg1 changes 743:749 acute and chronic changes 725:749 acute and chronic changes 725:749 Using miRNA microarray analysis, we observed acute and chronic changes in expression of several miRNAs. 25183011 5 29 theme OGA 847:849 arg1 mRNA 851:854 OGA mRNA 847:854 OGA mRNA 847:854 Here, we focused on miR-539 because it was predicted to target OGA mRNA. 25183011 3 30 theme molecular 597:605 arg1 mechanisms 607:616 molecular mechanisms 597:616 molecular mechanisms regulating these enzymes during heart failure 597:662 We recently reported reduced OGA expression in the failing heart, which is consistent with the pro-adaptive role of increased O-GlcNAcylation during heart failure; however, molecular mechanisms regulating these enzymes during heart failure remain unknown. 25183011 2 31 theme proteins 414:421 arg1 function 373:380 the function 369:380 the function of many nuclear and cytoplasmic proteins 369:421 One such signal, O-linked β-N-acetylglucosamine (O-GlcNAc), is an essential post-translational modification regulated by two enzymes, O-GlcNAc transferase and O-GlcNAcase (OGA), which modulate the function of many nuclear and cytoplasmic proteins. 25183011 0 32 theme failing 32:38 arg1 heart 40:44 failing heart 32:44 failing heart 32:44 MicroRNA-539 is up-regulated in failing heart, and suppresses O-GlcNAcase expression. 25183011 9 33 theme metabolic 1464:1472 arg1 diseases 1474:1481 other metabolic diseases 1458:1481 other metabolic diseases 1458:1481 Manipulation of miR-539 may represent a novel therapeutic target in the treatment of heart failure and other metabolic diseases. 25183011 3 34 theme heart 650:654 arg1 failure 656:662 heart failure 650:662 heart failure 650:662 We recently reported reduced OGA expression in the failing heart, which is consistent with the pro-adaptive role of increased O-GlcNAcylation during heart failure; however, molecular mechanisms regulating these enzymes during heart failure remain unknown. 25183011 3 35 from expression 457:466 arg1 heart 483:487 the failing heart 471:487 the failing heart 471:487 We recently reported reduced OGA expression in the failing heart, which is consistent with the pro-adaptive role of increased O-GlcNAcylation during heart failure; however, molecular mechanisms regulating these enzymes during heart failure remain unknown. 25183011 2 36 theme cytoplasmic 402:412 arg1 proteins 414:421 many nuclear and cytoplasmic proteins 385:421 many nuclear and cytoplasmic proteins 385:421 One such signal, O-linked β-N-acetylglucosamine (O-GlcNAc), is an essential post-translational modification regulated by two enzymes, O-GlcNAc transferase and O-GlcNAcase (OGA), which modulate the function of many nuclear and cytoplasmic proteins. 25183011 7 37 theme protein 1189:1195 arg1 expression 1197:1206 OGA protein expression 1185:1206 OGA protein expression 1185:1206 Overexpression of miR-539 in neonatal rat cardiomyocytes significantly suppressed OGA expression and consequently increased O-GlcNAcylation; conversely, the miR-539 inhibitor rescued OGA protein expression and restored O-GlcNAcylation. 25183011 6 38 theme overexpression 938:951 arg1 plasmid 953:959 miR-539 overexpression plasmid 930:959 miR-539 overexpression plasmid 930:959 Indeed, co-transfection of the OGA-3'UTR containing reporter plasmid and miR-539 overexpression plasmid significantly reduced reporter activity. 25183011 7 39 theme OGA 1084:1086 arg1 expression 1088:1097 OGA expression 1084:1097 OGA expression 1084:1097 Overexpression of miR-539 in neonatal rat cardiomyocytes significantly suppressed OGA expression and consequently increased O-GlcNAcylation; conversely, the miR-539 inhibitor rescued OGA protein expression and restored O-GlcNAcylation. 25183011 1 40 theme related 117:123 arg1 pathways 135:142 related signaling pathways 117:142 related signaling pathways 117:142 Derangements in metabolism and related signaling pathways characterize the failing heart. 25183011 6 41 theme miR-539 930:936 arg1 plasmid 953:959 miR-539 overexpression plasmid 930:959 miR-539 overexpression plasmid 930:959 Indeed, co-transfection of the OGA-3'UTR containing reporter plasmid and miR-539 overexpression plasmid significantly reduced reporter activity. 25183011 7 42 from Overexpression 1002:1015 arg1 cardiomyocytes 1044:1057 neonatal rat cardiomyocytes 1031:1057 neonatal rat cardiomyocytes 1031:1057 Overexpression of miR-539 in neonatal rat cardiomyocytes significantly suppressed OGA expression and consequently increased O-GlcNAcylation; conversely, the miR-539 inhibitor rescued OGA protein expression and restored O-GlcNAcylation. 25183011 1 43 theme signaling 125:133 arg1 pathways 135:142 related signaling pathways 117:142 related signaling pathways 117:142 Derangements in metabolism and related signaling pathways characterize the failing heart. 25183011 7 44 theme neonatal 1031:1038 arg1 cardiomyocytes 1044:1057 neonatal rat cardiomyocytes 1031:1057 neonatal rat cardiomyocytes 1031:1057 Overexpression of miR-539 in neonatal rat cardiomyocytes significantly suppressed OGA expression and consequently increased O-GlcNAcylation; conversely, the miR-539 inhibitor rescued OGA protein expression and restored O-GlcNAcylation. 25183011 8 45 theme first 1323:1327 arg1 miRNA 1329:1333 the first miRNA 1319:1333 the first miRNA that regulates OGA 1319:1352 In conclusion, this work identifies the first target of miR-539 in the heart and the first miRNA that regulates OGA. 25183011 7 46 theme rat 1040:1042 arg1 cardiomyocytes 1044:1057 neonatal rat cardiomyocytes 1031:1057 neonatal rat cardiomyocytes 1031:1057 Overexpression of miR-539 in neonatal rat cardiomyocytes significantly suppressed OGA expression and consequently increased O-GlcNAcylation; conversely, the miR-539 inhibitor rescued OGA protein expression and restored O-GlcNAcylation. 25183011 8 47 from miRNA 1329:1333 arg1 heart 1309:1313 the heart 1305:1313 the heart 1305:1313 In conclusion, this work identifies the first target of miR-539 in the heart and the first miRNA that regulates OGA. 25183011 1 48 theme failing 161:167 arg1 heart 169:173 the failing heart 157:173 the failing heart 157:173 Derangements in metabolism and related signaling pathways characterize the failing heart. 25183011 1 49 from Derangements 86:97 arg1 pathways 135:142 related signaling pathways 117:142 related signaling pathways 117:142 Derangements in metabolism and related signaling pathways characterize the failing heart. 25183011 1 49 from Derangements 86:97 arg1 metabolism 102:111 metabolism 102:111 metabolism 102:111 Derangements in metabolism and related signaling pathways characterize the failing heart. 25183011 9 50 theme heart 1440:1444 arg1 failure 1446:1452 heart failure 1440:1452 heart failure 1440:1452 Manipulation of miR-539 may represent a novel therapeutic target in the treatment of heart failure and other metabolic diseases. 25183011 0 51 theme O-GlcNAcase 62:72 arg1 expression 74:83 O-GlcNAcase expression 62:83 O-GlcNAcase expression 62:83 MicroRNA-539 is up-regulated in failing heart, and suppresses O-GlcNAcase expression. 25183011 2 52 theme O-linked 193:200 arg1 β-N-acetylglucosamine 202:222 O-linked β-N-acetylglucosamine 193:222 O-linked β-N-acetylglucosamine (O-GlcNAc) 193:233 One such signal, O-linked β-N-acetylglucosamine (O-GlcNAc), is an essential post-translational modification regulated by two enzymes, O-GlcNAc transferase and O-GlcNAcase (OGA), which modulate the function of many nuclear and cytoplasmic proteins. 25183011 2 52 theme O-linked 193:200 arg1 One 176:178 One 176:178 One 176:178 One such signal, O-linked β-N-acetylglucosamine (O-GlcNAc), is an essential post-translational modification regulated by two enzymes, O-GlcNAc transferase and O-GlcNAcase (OGA), which modulate the function of many nuclear and cytoplasmic proteins. 25183011 2 52 theme O-linked 193:200 arg1 O-GlcNAc 225:232 O-GlcNAc 225:232 O-GlcNAc 225:232 One such signal, O-linked β-N-acetylglucosamine (O-GlcNAc), is an essential post-translational modification regulated by two enzymes, O-GlcNAc transferase and O-GlcNAcase (OGA), which modulate the function of many nuclear and cytoplasmic proteins. 25183011 2 53 theme post-translational 252:269 arg1 One 176:178 One 176:178 One 176:178 One such signal, O-linked β-N-acetylglucosamine (O-GlcNAc), is an essential post-translational modification regulated by two enzymes, O-GlcNAc transferase and O-GlcNAcase (OGA), which modulate the function of many nuclear and cytoplasmic proteins. 25183011 2 53 theme post-translational 252:269 arg1 modification 271:282 an essential post-translational modification 239:282 an essential post-translational modification regulated by two enzymes, O-GlcNAc transferase and O-GlcNAcase (OGA), which modulate the function of many nuclear and cytoplasmic proteins 239:421 One such signal, O-linked β-N-acetylglucosamine (O-GlcNAc), is an essential post-translational modification regulated by two enzymes, O-GlcNAc transferase and O-GlcNAcase (OGA), which modulate the function of many nuclear and cytoplasmic proteins. 25183011 7 54 theme miR-539 1020:1026 arg1 Overexpression 1002:1015 Overexpression 1002:1015 Overexpression of miR-539 in neonatal rat cardiomyocytes 1002:1057 Overexpression of miR-539 in neonatal rat cardiomyocytes significantly suppressed OGA expression and consequently increased O-GlcNAcylation; conversely, the miR-539 inhibitor rescued OGA protein expression and restored O-GlcNAcylation. 25183011 3 55 theme OGA 453:455 arg1 expression 457:466 reduced OGA expression 445:466 reduced OGA expression 445:466 We recently reported reduced OGA expression in the failing heart, which is consistent with the pro-adaptive role of increased O-GlcNAcylation during heart failure; however, molecular mechanisms regulating these enzymes during heart failure remain unknown. 25183011 9 56 theme failure 1446:1452 arg1 treatment 1427:1435 the treatment 1423:1435 the treatment of heart failure and other metabolic diseases 1423:1481 Manipulation of miR-539 may represent a novel therapeutic target in the treatment of heart failure and other metabolic diseases. 25183011 8 57 theme miR-539 1294:1300 arg1 target 1284:1289 the first target 1274:1289 the first target of miR-539 in the heart 1274:1313 In conclusion, this work identifies the first target of miR-539 in the heart and the first miRNA that regulates OGA. 25183011 8 57 theme miR-539 1294:1300 arg1 miRNA 1329:1333 the first miRNA 1319:1333 the first miRNA that regulates OGA 1319:1352 In conclusion, this work identifies the first target of miR-539 in the heart and the first miRNA that regulates OGA. 25183011 2 58 theme essential 242:250 arg1 One 176:178 One 176:178 One 176:178 One such signal, O-linked β-N-acetylglucosamine (O-GlcNAc), is an essential post-translational modification regulated by two enzymes, O-GlcNAc transferase and O-GlcNAcase (OGA), which modulate the function of many nuclear and cytoplasmic proteins. 25183011 2 58 theme essential 242:250 arg1 modification 271:282 an essential post-translational modification 239:282 an essential post-translational modification regulated by two enzymes, O-GlcNAc transferase and O-GlcNAcase (OGA), which modulate the function of many nuclear and cytoplasmic proteins 239:421 One such signal, O-linked β-N-acetylglucosamine (O-GlcNAc), is an essential post-translational modification regulated by two enzymes, O-GlcNAc transferase and O-GlcNAcase (OGA), which modulate the function of many nuclear and cytoplasmic proteins. 25183011 3 59 theme pro-adaptive 519:530 arg1 role 532:535 the pro-adaptive role 515:535 the pro-adaptive role of increased O-GlcNAcylation during heart failure 515:585 We recently reported reduced OGA expression in the failing heart, which is consistent with the pro-adaptive role of increased O-GlcNAcylation during heart failure; however, molecular mechanisms regulating these enzymes during heart failure remain unknown. 25183011 9 60 from target 1413:1418 arg1 treatment 1427:1435 the treatment 1423:1435 the treatment of heart failure and other metabolic diseases 1423:1481 Manipulation of miR-539 may represent a novel therapeutic target in the treatment of heart failure and other metabolic diseases. 25176179 1 0 theme subsequent 244:253 arg1 ischemia 281:288 sustained ischemia 271:288 sustained ischemia 271:288 Ischemic preconditioning is an intrinsic process in which preconditioning ischemia (ischemia of shorter duration) protects the organs against the subsequent index ischemia (sustained ischemia). 25176179 1 0 theme subsequent 244:253 arg1 ischemia 261:268 the subsequent index ischemia 240:268 the subsequent index ischemia (sustained ischemia) 240:289 Ischemic preconditioning is an intrinsic process in which preconditioning ischemia (ischemia of shorter duration) protects the organs against the subsequent index ischemia (sustained ischemia). 25176179 7 1 theme drug-eluting 1495:1506 arg1 surgery 1395:1401 graft surgery 1389:1401 graft surgery 1389:1401 The institution of RIPC is beneficial in mitigating myocardial injury in patients undergoing various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery. 25176179 7 1 theme drug-eluting 1495:1506 arg1 implantation 1514:1525 drug-eluting stent implantation 1495:1525 drug-eluting stent implantation 1495:1525 The institution of RIPC is beneficial in mitigating myocardial injury in patients undergoing various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery. 25176179 7 2 theme coronary 1451:1458 arg1 surgery 1395:1401 graft surgery 1389:1401 graft surgery 1389:1401 The institution of RIPC is beneficial in mitigating myocardial injury in patients undergoing various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery. 25176179 7 2 theme coronary 1451:1458 arg1 intervention 1460:1471 percutaneous coronary intervention 1438:1471 percutaneous coronary intervention 1438:1471 The institution of RIPC is beneficial in mitigating myocardial injury in patients undergoing various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery. 25176179 6 3 theme 3-4 1155:1157 arg1 periods 1171:1177 3-4 consecutive periods 1155:1177 3-4 consecutive periods to precondition the tissue 1155:1204 This cycle is repeated for 3-4 consecutive periods to precondition the tissue and improve the survival. 25176179 9 4 theme possible 1983:1990 arg1 mechanisms 1992:2001 the other possible mechanisms 1973:2001 the other possible mechanisms responsible for producing multi-organ protection during RIPC 1973:2062 However, comprehensive studies are required to elucidate the other possible mechanisms responsible for producing multi-organ protection during RIPC. 25176179 8 5 theme O-linked 1759:1766 arg1 O-GlcNAc 1791:1798 O-GlcNAc 1791:1798 O-GlcNAc 1791:1798 The involvement of hypoxia inducible factor-1α (HIF-1α), ATP-sensitive potassium channels, signal transducer and activator of transcription (STAT), matrix metalloproteinases, O-linked β-N-acetylglucosamine (O-GlcNAc) levels, autonomous nervous system in mediating RIPC-induced cardioprotective effects has been explored clinically. 25176179 8 5 theme O-linked 1759:1766 arg1 β-N-acetylglucosamine 1768:1788 O-linked β-N-acetylglucosamine 1759:1788 O-linked β-N-acetylglucosamine (O-GlcNAc) levels 1759:1806 The involvement of hypoxia inducible factor-1α (HIF-1α), ATP-sensitive potassium channels, signal transducer and activator of transcription (STAT), matrix metalloproteinases, O-linked β-N-acetylglucosamine (O-GlcNAc) levels, autonomous nervous system in mediating RIPC-induced cardioprotective effects has been explored clinically. 25176179 7 6 theme heart 1474:1478 arg1 surgery 1486:1492 heart valve surgery 1474:1492 heart valve surgery 1474:1492 The institution of RIPC is beneficial in mitigating myocardial injury in patients undergoing various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery. 25176179 7 6 theme heart 1474:1478 arg1 surgery 1395:1401 graft surgery 1389:1401 graft surgery 1389:1401 The institution of RIPC is beneficial in mitigating myocardial injury in patients undergoing various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery. 25176179 7 7 theme aneurysm 1421:1428 arg1 repair 1430:1435 abdominal aortic aneurysm repair 1404:1435 abdominal aortic aneurysm repair 1404:1435 The institution of RIPC is beneficial in mitigating myocardial injury in patients undergoing various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery. 25176179 7 7 theme aneurysm 1421:1428 arg1 surgery 1395:1401 graft surgery 1389:1401 graft surgery 1389:1401 The institution of RIPC is beneficial in mitigating myocardial injury in patients undergoing various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery. 25176179 9 8 theme responsible 2003:2013 arg1 mechanisms 1992:2001 the other possible mechanisms 1973:2001 the other possible mechanisms responsible for producing multi-organ protection during RIPC 1973:2062 However, comprehensive studies are required to elucidate the other possible mechanisms responsible for producing multi-organ protection during RIPC. 25176179 2 9 theme ischemic 299:306 arg1 approach 358:365 an innovative treatment approach 334:365 an innovative treatment approach in which interspersed cycles of preconditioning ischemia followed by reperfusion to a remote organ (other than target organ) protect the target organ against index ischemia and reperfusion-induced injury 334:569 Remote ischemic preconditioning (RIPC) is an innovative treatment approach in which interspersed cycles of preconditioning ischemia followed by reperfusion to a remote organ (other than target organ) protect the target organ against index ischemia and reperfusion-induced injury. 25176179 2 9 theme ischemic 299:306 arg1 RIPC 325:328 RIPC 325:328 RIPC 325:328 Remote ischemic preconditioning (RIPC) is an innovative treatment approach in which interspersed cycles of preconditioning ischemia followed by reperfusion to a remote organ (other than target organ) protect the target organ against index ischemia and reperfusion-induced injury. 25176179 2 9 theme ischemic 299:306 arg1 preconditioning 308:322 Remote ischemic preconditioning 292:322 Remote ischemic preconditioning (RIPC) 292:329 Remote ischemic preconditioning (RIPC) is an innovative treatment approach in which interspersed cycles of preconditioning ischemia followed by reperfusion to a remote organ (other than target organ) protect the target organ against index ischemia and reperfusion-induced injury. 25176179 7 10 theme abdominal 1404:1412 arg1 aneurysm 1421:1428 abdominal aortic aneurysm 1404:1428 abdominal aortic aneurysm repair 1404:1435 The institution of RIPC is beneficial in mitigating myocardial injury in patients undergoing various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery. 25176179 1 11 theme shorter 194:200 arg1 duration 202:209 shorter duration 194:209 shorter duration 194:209 Ischemic preconditioning is an intrinsic process in which preconditioning ischemia (ischemia of shorter duration) protects the organs against the subsequent index ischemia (sustained ischemia). 25176179 2 12 theme index 525:529 arg1 ischemia 531:538 index ischemia 525:538 index ischemia 525:538 Remote ischemic preconditioning (RIPC) is an innovative treatment approach in which interspersed cycles of preconditioning ischemia followed by reperfusion to a remote organ (other than target organ) protect the target organ against index ischemia and reperfusion-induced injury. 25176179 7 13 dep artery 1375:1380 arg1 repair 1430:1435 abdominal aortic aneurysm repair 1404:1435 abdominal aortic aneurysm repair 1404:1435 The institution of RIPC is beneficial in mitigating myocardial injury in patients undergoing various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery. 25176179 7 13 dep artery 1375:1380 arg1 surgery 1575:1581 elective decompression surgery 1552:1581 elective decompression surgery 1552:1581 The institution of RIPC is beneficial in mitigating myocardial injury in patients undergoing various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery. 25176179 7 13 dep artery 1375:1380 arg1 bypass 1382:1387 bypass 1382:1387 bypass 1382:1387 The institution of RIPC is beneficial in mitigating myocardial injury in patients undergoing various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery. 25176179 7 13 dep artery 1375:1380 arg1 surgery 1486:1492 heart valve surgery 1474:1492 heart valve surgery 1474:1492 The institution of RIPC is beneficial in mitigating myocardial injury in patients undergoing various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery. 25176179 7 13 dep artery 1375:1380 arg1 surgery 1395:1401 graft surgery 1389:1401 graft surgery 1389:1401 The institution of RIPC is beneficial in mitigating myocardial injury in patients undergoing various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery. 25176179 7 13 dep artery 1375:1380 arg1 transplantation 1535:1549 kidney transplantation 1528:1549 kidney transplantation 1528:1549 The institution of RIPC is beneficial in mitigating myocardial injury in patients undergoing various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery. 25176179 7 13 dep artery 1375:1380 arg1 intervention 1460:1471 percutaneous coronary intervention 1438:1471 percutaneous coronary intervention 1438:1471 The institution of RIPC is beneficial in mitigating myocardial injury in patients undergoing various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery. 25176179 7 13 dep artery 1375:1380 arg1 implantation 1514:1525 drug-eluting stent implantation 1495:1525 drug-eluting stent implantation 1495:1525 The institution of RIPC is beneficial in mitigating myocardial injury in patients undergoing various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery. 25176179 6 14 dep precondition 1182:1193 arg1 tissue 1199:1204 the tissue 1195:1204 the tissue 1195:1204 This cycle is repeated for 3-4 consecutive periods to precondition the tissue and improve the survival. 25176179 3 15 theme various 580:586 arg1 organs 588:593 various organs 580:593 various organs 580:593 RIPC of various organs to provide multi-organ salvage became a successful approach in numerous species of animals. 25176179 8 16 theme nervous 1820:1826 arg1 factor-1α 1621:1629 hypoxia inducible factor-1α 1603:1629 hypoxia inducible factor-1α (HIF-1α) 1603:1638 The involvement of hypoxia inducible factor-1α (HIF-1α), ATP-sensitive potassium channels, signal transducer and activator of transcription (STAT), matrix metalloproteinases, O-linked β-N-acetylglucosamine (O-GlcNAc) levels, autonomous nervous system in mediating RIPC-induced cardioprotective effects has been explored clinically. 25176179 8 16 theme nervous 1820:1826 arg1 system 1828:1833 autonomous nervous system 1809:1833 autonomous nervous system 1809:1833 The involvement of hypoxia inducible factor-1α (HIF-1α), ATP-sensitive potassium channels, signal transducer and activator of transcription (STAT), matrix metalloproteinases, O-linked β-N-acetylglucosamine (O-GlcNAc) levels, autonomous nervous system in mediating RIPC-induced cardioprotective effects has been explored clinically. 25176179 7 17 theme coronary 1366:1373 arg1 artery 1375:1380 coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery 1366:1581 coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery 1366:1581 The institution of RIPC is beneficial in mitigating myocardial injury in patients undergoing various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery. 25176179 4 18 from injury 825:830 arg1 myocardium 868:877 myocardium 868:877 myocardium 868:877 Consequently, the concept of RIPC evolved in clinical setups, and provided beneficial effects in alleviating ischemia-reperfusion-induced injury in various remote organs, including myocardium. 25176179 4 18 from injury 825:830 arg1 organs 850:855 various remote organs 835:855 various remote organs 835:855 Consequently, the concept of RIPC evolved in clinical setups, and provided beneficial effects in alleviating ischemia-reperfusion-induced injury in various remote organs, including myocardium. 25176179 3 19 theme multi-organ 606:616 arg1 salvage 618:624 multi-organ salvage 606:624 multi-organ salvage 606:624 RIPC of various organs to provide multi-organ salvage became a successful approach in numerous species of animals. 25176179 8 20 theme RIPC-induced 1848:1859 arg1 effects 1878:1884 RIPC-induced cardioprotective effects 1848:1884 RIPC-induced cardioprotective effects 1848:1884 The involvement of hypoxia inducible factor-1α (HIF-1α), ATP-sensitive potassium channels, signal transducer and activator of transcription (STAT), matrix metalloproteinases, O-linked β-N-acetylglucosamine (O-GlcNAc) levels, autonomous nervous system in mediating RIPC-induced cardioprotective effects has been explored clinically. 25176179 2 21 theme target 478:483 arg1 organ 485:489 target organ 478:489 target organ 478:489 Remote ischemic preconditioning (RIPC) is an innovative treatment approach in which interspersed cycles of preconditioning ischemia followed by reperfusion to a remote organ (other than target organ) protect the target organ against index ischemia and reperfusion-induced injury. 25176179 0 22 theme concept 63:69 arg1 evolution 50:58 evolution 50:58 RIPC for multiorgan salvage in clinical settings: evolution of concept, evidences and mechanisms. 0:96 RIPC for multiorgan salvage in clinical settings: evolution of concept, evidences and mechanisms. 25176179 0 23 from RIPC 0:3 arg1 settings 40:47 clinical settings 31:47 clinical settings 31:47 RIPC for multiorgan salvage in clinical settings: evolution of concept, evidences and mechanisms. 25176179 0 24 theme evidences 72:80 arg1 evolution 50:58 evolution 50:58 RIPC for multiorgan salvage in clinical settings: evolution of concept, evidences and mechanisms. 0:96 RIPC for multiorgan salvage in clinical settings: evolution of concept, evidences and mechanisms. 25176179 5 25 theme 5 1087:1087 arg1 min 1089:1091 min 1089:1091 min 1089:1091 Clinically, RIPC stimulus is generally delivered by inflating the blood pressure cuff tied on the upper arm 20 mm greater than the systolic blood pressure, rendering the forearm ischemic for 5 min, followed 5 min reperfusion by deflating the cuff. 25176179 0 26 theme mechanisms 86:95 arg1 evolution 50:58 evolution 50:58 RIPC for multiorgan salvage in clinical settings: evolution of concept, evidences and mechanisms. 0:96 RIPC for multiorgan salvage in clinical settings: evolution of concept, evidences and mechanisms. 25176179 7 27 theme surgical 1333:1340 arg1 interventions 1342:1354 various surgical interventions 1325:1354 various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery 1325:1581 The institution of RIPC is beneficial in mitigating myocardial injury in patients undergoing various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery. 25176179 7 27 theme surgical 1333:1340 arg1 artery 1375:1380 coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery 1366:1581 coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery 1366:1581 The institution of RIPC is beneficial in mitigating myocardial injury in patients undergoing various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery. 25176179 4 28 theme clinical 732:739 arg1 setups 741:746 clinical setups 732:746 clinical setups 732:746 Consequently, the concept of RIPC evolved in clinical setups, and provided beneficial effects in alleviating ischemia-reperfusion-induced injury in various remote organs, including myocardium. 25176179 0 29 theme multiorgan 9:18 arg1 salvage 20:26 multiorgan salvage 9:26 multiorgan salvage 9:26 RIPC for multiorgan salvage in clinical settings: evolution of concept, evidences and mechanisms. 25176179 4 30 theme various 835:841 arg1 myocardium 868:877 myocardium 868:877 myocardium 868:877 Consequently, the concept of RIPC evolved in clinical setups, and provided beneficial effects in alleviating ischemia-reperfusion-induced injury in various remote organs, including myocardium. 25176179 4 30 theme various 835:841 arg1 organs 850:855 various remote organs 835:855 various remote organs 835:855 Consequently, the concept of RIPC evolved in clinical setups, and provided beneficial effects in alleviating ischemia-reperfusion-induced injury in various remote organs, including myocardium. 25176179 2 31 theme preconditioning 399:413 arg1 ischemia 415:422 preconditioning ischemia 399:422 preconditioning ischemia 399:422 Remote ischemic preconditioning (RIPC) is an innovative treatment approach in which interspersed cycles of preconditioning ischemia followed by reperfusion to a remote organ (other than target organ) protect the target organ against index ischemia and reperfusion-induced injury. 25176179 7 32 theme elective 1552:1559 arg1 surgery 1395:1401 graft surgery 1389:1401 graft surgery 1389:1401 The institution of RIPC is beneficial in mitigating myocardial injury in patients undergoing various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery. 25176179 7 32 theme elective 1552:1559 arg1 surgery 1575:1581 elective decompression surgery 1552:1581 elective decompression surgery 1552:1581 The institution of RIPC is beneficial in mitigating myocardial injury in patients undergoing various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery. 25176179 7 33 theme myocardial 1284:1293 arg1 injury 1295:1300 myocardial injury 1284:1300 myocardial injury in patients undergoing various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery 1284:1581 The institution of RIPC is beneficial in mitigating myocardial injury in patients undergoing various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery. 25176179 8 34 theme inducible 1611:1619 arg1 activator 1697:1705 activator 1697:1705 activator of transcription 1697:1722 The involvement of hypoxia inducible factor-1α (HIF-1α), ATP-sensitive potassium channels, signal transducer and activator of transcription (STAT), matrix metalloproteinases, O-linked β-N-acetylglucosamine (O-GlcNAc) levels, autonomous nervous system in mediating RIPC-induced cardioprotective effects has been explored clinically. 25176179 8 34 theme inducible 1611:1619 arg1 system 1828:1833 autonomous nervous system 1809:1833 autonomous nervous system 1809:1833 The involvement of hypoxia inducible factor-1α (HIF-1α), ATP-sensitive potassium channels, signal transducer and activator of transcription (STAT), matrix metalloproteinases, O-linked β-N-acetylglucosamine (O-GlcNAc) levels, autonomous nervous system in mediating RIPC-induced cardioprotective effects has been explored clinically. 25176179 8 34 theme inducible 1611:1619 arg1 factor-1α 1621:1629 hypoxia inducible factor-1α 1603:1629 hypoxia inducible factor-1α (HIF-1α) 1603:1638 The involvement of hypoxia inducible factor-1α (HIF-1α), ATP-sensitive potassium channels, signal transducer and activator of transcription (STAT), matrix metalloproteinases, O-linked β-N-acetylglucosamine (O-GlcNAc) levels, autonomous nervous system in mediating RIPC-induced cardioprotective effects has been explored clinically. 25176179 8 34 theme inducible 1611:1619 arg1 metalloproteinases 1739:1756 matrix metalloproteinases 1732:1756 matrix metalloproteinases 1732:1756 The involvement of hypoxia inducible factor-1α (HIF-1α), ATP-sensitive potassium channels, signal transducer and activator of transcription (STAT), matrix metalloproteinases, O-linked β-N-acetylglucosamine (O-GlcNAc) levels, autonomous nervous system in mediating RIPC-induced cardioprotective effects has been explored clinically. 25176179 8 34 theme inducible 1611:1619 arg1 channels 1665:1672 ATP-sensitive potassium channels 1641:1672 ATP-sensitive potassium channels 1641:1672 The involvement of hypoxia inducible factor-1α (HIF-1α), ATP-sensitive potassium channels, signal transducer and activator of transcription (STAT), matrix metalloproteinases, O-linked β-N-acetylglucosamine (O-GlcNAc) levels, autonomous nervous system in mediating RIPC-induced cardioprotective effects has been explored clinically. 25176179 8 34 theme inducible 1611:1619 arg1 HIF-1α 1632:1637 HIF-1α 1632:1637 HIF-1α 1632:1637 The involvement of hypoxia inducible factor-1α (HIF-1α), ATP-sensitive potassium channels, signal transducer and activator of transcription (STAT), matrix metalloproteinases, O-linked β-N-acetylglucosamine (O-GlcNAc) levels, autonomous nervous system in mediating RIPC-induced cardioprotective effects has been explored clinically. 25176179 8 34 theme inducible 1611:1619 arg1 levels 1801:1806 O-linked β-N-acetylglucosamine (O-GlcNAc) levels 1759:1806 O-linked β-N-acetylglucosamine (O-GlcNAc) levels 1759:1806 The involvement of hypoxia inducible factor-1α (HIF-1α), ATP-sensitive potassium channels, signal transducer and activator of transcription (STAT), matrix metalloproteinases, O-linked β-N-acetylglucosamine (O-GlcNAc) levels, autonomous nervous system in mediating RIPC-induced cardioprotective effects has been explored clinically. 25176179 8 34 theme inducible 1611:1619 arg1 transducer 1682:1691 signal transducer 1675:1691 signal transducer 1675:1691 The involvement of hypoxia inducible factor-1α (HIF-1α), ATP-sensitive potassium channels, signal transducer and activator of transcription (STAT), matrix metalloproteinases, O-linked β-N-acetylglucosamine (O-GlcNAc) levels, autonomous nervous system in mediating RIPC-induced cardioprotective effects has been explored clinically. 25176179 3 35 theme successful 635:644 arg1 approach 646:653 a successful approach 633:653 a successful approach in numerous species of animals 633:684 RIPC of various organs to provide multi-organ salvage became a successful approach in numerous species of animals. 25176179 7 36 from injury 1295:1300 arg1 patients 1305:1312 patients 1305:1312 patients undergoing various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery 1305:1581 The institution of RIPC is beneficial in mitigating myocardial injury in patients undergoing various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery. 25176179 3 37 theme animals 678:684 arg1 species 667:673 numerous species 658:673 numerous species of animals 658:684 RIPC of various organs to provide multi-organ salvage became a successful approach in numerous species of animals. 25176179 7 38 theme stent 1508:1512 arg1 surgery 1395:1401 graft surgery 1389:1401 graft surgery 1389:1401 The institution of RIPC is beneficial in mitigating myocardial injury in patients undergoing various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery. 25176179 7 38 theme stent 1508:1512 arg1 implantation 1514:1525 drug-eluting stent implantation 1495:1525 drug-eluting stent implantation 1495:1525 The institution of RIPC is beneficial in mitigating myocardial injury in patients undergoing various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery. 25176179 5 39 theme systolic 1011:1018 arg1 pressure 1026:1033 the systolic blood pressure 1007:1033 the systolic blood pressure 1007:1033 Clinically, RIPC stimulus is generally delivered by inflating the blood pressure cuff tied on the upper arm 20 mm greater than the systolic blood pressure, rendering the forearm ischemic for 5 min, followed 5 min reperfusion by deflating the cuff. 25176179 8 40 theme ATP-sensitive 1641:1653 arg1 factor-1α 1621:1629 hypoxia inducible factor-1α 1603:1629 hypoxia inducible factor-1α (HIF-1α) 1603:1638 The involvement of hypoxia inducible factor-1α (HIF-1α), ATP-sensitive potassium channels, signal transducer and activator of transcription (STAT), matrix metalloproteinases, O-linked β-N-acetylglucosamine (O-GlcNAc) levels, autonomous nervous system in mediating RIPC-induced cardioprotective effects has been explored clinically. 25176179 8 40 theme ATP-sensitive 1641:1653 arg1 channels 1665:1672 ATP-sensitive potassium channels 1641:1672 ATP-sensitive potassium channels 1641:1672 The involvement of hypoxia inducible factor-1α (HIF-1α), ATP-sensitive potassium channels, signal transducer and activator of transcription (STAT), matrix metalloproteinases, O-linked β-N-acetylglucosamine (O-GlcNAc) levels, autonomous nervous system in mediating RIPC-induced cardioprotective effects has been explored clinically. 25176179 2 41 theme innovative 337:346 arg1 preconditioning 308:322 Remote ischemic preconditioning 292:322 Remote ischemic preconditioning (RIPC) 292:329 Remote ischemic preconditioning (RIPC) is an innovative treatment approach in which interspersed cycles of preconditioning ischemia followed by reperfusion to a remote organ (other than target organ) protect the target organ against index ischemia and reperfusion-induced injury. 25176179 2 41 theme innovative 337:346 arg1 approach 358:365 an innovative treatment approach 334:365 an innovative treatment approach in which interspersed cycles of preconditioning ischemia followed by reperfusion to a remote organ (other than target organ) protect the target organ against index ischemia and reperfusion-induced injury 334:569 Remote ischemic preconditioning (RIPC) is an innovative treatment approach in which interspersed cycles of preconditioning ischemia followed by reperfusion to a remote organ (other than target organ) protect the target organ against index ischemia and reperfusion-induced injury. 25176179 1 42 theme index 255:259 arg1 ischemia 281:288 sustained ischemia 271:288 sustained ischemia 271:288 Ischemic preconditioning is an intrinsic process in which preconditioning ischemia (ischemia of shorter duration) protects the organs against the subsequent index ischemia (sustained ischemia). 25176179 1 42 theme index 255:259 arg1 ischemia 261:268 the subsequent index ischemia 240:268 the subsequent index ischemia (sustained ischemia) 240:289 Ischemic preconditioning is an intrinsic process in which preconditioning ischemia (ischemia of shorter duration) protects the organs against the subsequent index ischemia (sustained ischemia). 25176179 7 43 theme valve 1480:1484 arg1 surgery 1486:1492 heart valve surgery 1474:1492 heart valve surgery 1474:1492 The institution of RIPC is beneficial in mitigating myocardial injury in patients undergoing various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery. 25176179 7 43 theme valve 1480:1484 arg1 surgery 1395:1401 graft surgery 1389:1401 graft surgery 1389:1401 The institution of RIPC is beneficial in mitigating myocardial injury in patients undergoing various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery. 25176179 6 44 theme consecutive 1159:1169 arg1 periods 1171:1177 3-4 consecutive periods 1155:1177 3-4 consecutive periods to precondition the tissue 1155:1204 This cycle is repeated for 3-4 consecutive periods to precondition the tissue and improve the survival. 25176179 9 45 theme other 1977:1981 arg1 mechanisms 1992:2001 the other possible mechanisms 1973:2001 the other possible mechanisms responsible for producing multi-organ protection during RIPC 1973:2062 However, comprehensive studies are required to elucidate the other possible mechanisms responsible for producing multi-organ protection during RIPC. 25176179 8 46 theme signal 1675:1680 arg1 STAT 1725:1728 STAT 1725:1728 STAT 1725:1728 The involvement of hypoxia inducible factor-1α (HIF-1α), ATP-sensitive potassium channels, signal transducer and activator of transcription (STAT), matrix metalloproteinases, O-linked β-N-acetylglucosamine (O-GlcNAc) levels, autonomous nervous system in mediating RIPC-induced cardioprotective effects has been explored clinically. 25176179 8 46 theme signal 1675:1680 arg1 factor-1α 1621:1629 hypoxia inducible factor-1α 1603:1629 hypoxia inducible factor-1α (HIF-1α) 1603:1638 The involvement of hypoxia inducible factor-1α (HIF-1α), ATP-sensitive potassium channels, signal transducer and activator of transcription (STAT), matrix metalloproteinases, O-linked β-N-acetylglucosamine (O-GlcNAc) levels, autonomous nervous system in mediating RIPC-induced cardioprotective effects has been explored clinically. 25176179 8 46 theme signal 1675:1680 arg1 transducer 1682:1691 signal transducer 1675:1691 signal transducer 1675:1691 The involvement of hypoxia inducible factor-1α (HIF-1α), ATP-sensitive potassium channels, signal transducer and activator of transcription (STAT), matrix metalloproteinases, O-linked β-N-acetylglucosamine (O-GlcNAc) levels, autonomous nervous system in mediating RIPC-induced cardioprotective effects has been explored clinically. 25176179 3 47 from approach 646:653 arg1 species 667:673 numerous species 658:673 numerous species of animals 658:684 RIPC of various organs to provide multi-organ salvage became a successful approach in numerous species of animals. 25176179 8 48 theme matrix 1732:1737 arg1 factor-1α 1621:1629 hypoxia inducible factor-1α 1603:1629 hypoxia inducible factor-1α (HIF-1α) 1603:1638 The involvement of hypoxia inducible factor-1α (HIF-1α), ATP-sensitive potassium channels, signal transducer and activator of transcription (STAT), matrix metalloproteinases, O-linked β-N-acetylglucosamine (O-GlcNAc) levels, autonomous nervous system in mediating RIPC-induced cardioprotective effects has been explored clinically. 25176179 8 48 theme matrix 1732:1737 arg1 metalloproteinases 1739:1756 matrix metalloproteinases 1732:1756 matrix metalloproteinases 1732:1756 The involvement of hypoxia inducible factor-1α (HIF-1α), ATP-sensitive potassium channels, signal transducer and activator of transcription (STAT), matrix metalloproteinases, O-linked β-N-acetylglucosamine (O-GlcNAc) levels, autonomous nervous system in mediating RIPC-induced cardioprotective effects has been explored clinically. 25176179 1 49 theme preconditioning 156:170 arg1 ischemia 172:179 preconditioning ischemia 156:179 preconditioning ischemia (ischemia of shorter duration) 156:210 Ischemic preconditioning is an intrinsic process in which preconditioning ischemia (ischemia of shorter duration) protects the organs against the subsequent index ischemia (sustained ischemia). 25176179 7 50 theme percutaneous 1438:1449 arg1 surgery 1395:1401 graft surgery 1389:1401 graft surgery 1389:1401 The institution of RIPC is beneficial in mitigating myocardial injury in patients undergoing various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery. 25176179 7 50 theme percutaneous 1438:1449 arg1 intervention 1460:1471 percutaneous coronary intervention 1438:1471 percutaneous coronary intervention 1438:1471 The institution of RIPC is beneficial in mitigating myocardial injury in patients undergoing various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery. 25176179 5 51 theme RIPC 892:895 arg1 stimulus 897:904 RIPC stimulus 892:904 RIPC stimulus 892:904 Clinically, RIPC stimulus is generally delivered by inflating the blood pressure cuff tied on the upper arm 20 mm greater than the systolic blood pressure, rendering the forearm ischemic for 5 min, followed 5 min reperfusion by deflating the cuff. 25176179 1 52 dep ischemia 172:179 arg1 ischemia 182:189 ischemia 182:189 ischemia of shorter duration 182:209 Ischemic preconditioning is an intrinsic process in which preconditioning ischemia (ischemia of shorter duration) protects the organs against the subsequent index ischemia (sustained ischemia). 25176179 2 53 theme Remote 292:297 arg1 approach 358:365 an innovative treatment approach 334:365 an innovative treatment approach in which interspersed cycles of preconditioning ischemia followed by reperfusion to a remote organ (other than target organ) protect the target organ against index ischemia and reperfusion-induced injury 334:569 Remote ischemic preconditioning (RIPC) is an innovative treatment approach in which interspersed cycles of preconditioning ischemia followed by reperfusion to a remote organ (other than target organ) protect the target organ against index ischemia and reperfusion-induced injury. 25176179 2 53 theme Remote 292:297 arg1 RIPC 325:328 RIPC 325:328 RIPC 325:328 Remote ischemic preconditioning (RIPC) is an innovative treatment approach in which interspersed cycles of preconditioning ischemia followed by reperfusion to a remote organ (other than target organ) protect the target organ against index ischemia and reperfusion-induced injury. 25176179 2 53 theme Remote 292:297 arg1 preconditioning 308:322 Remote ischemic preconditioning 292:322 Remote ischemic preconditioning (RIPC) 292:329 Remote ischemic preconditioning (RIPC) is an innovative treatment approach in which interspersed cycles of preconditioning ischemia followed by reperfusion to a remote organ (other than target organ) protect the target organ against index ischemia and reperfusion-induced injury. 25176179 8 54 theme β-N-acetylglucosamine 1768:1788 arg1 factor-1α 1621:1629 hypoxia inducible factor-1α 1603:1629 hypoxia inducible factor-1α (HIF-1α) 1603:1638 The involvement of hypoxia inducible factor-1α (HIF-1α), ATP-sensitive potassium channels, signal transducer and activator of transcription (STAT), matrix metalloproteinases, O-linked β-N-acetylglucosamine (O-GlcNAc) levels, autonomous nervous system in mediating RIPC-induced cardioprotective effects has been explored clinically. 25176179 8 54 theme β-N-acetylglucosamine 1768:1788 arg1 levels 1801:1806 O-linked β-N-acetylglucosamine (O-GlcNAc) levels 1759:1806 O-linked β-N-acetylglucosamine (O-GlcNAc) levels 1759:1806 The involvement of hypoxia inducible factor-1α (HIF-1α), ATP-sensitive potassium channels, signal transducer and activator of transcription (STAT), matrix metalloproteinases, O-linked β-N-acetylglucosamine (O-GlcNAc) levels, autonomous nervous system in mediating RIPC-induced cardioprotective effects has been explored clinically. 25176179 7 55 theme aortic 1414:1419 arg1 aneurysm 1421:1428 abdominal aortic aneurysm 1404:1428 abdominal aortic aneurysm repair 1404:1435 The institution of RIPC is beneficial in mitigating myocardial injury in patients undergoing various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery. 25176179 9 56 theme multi-organ 2029:2039 arg1 protection 2041:2050 multi-organ protection 2029:2050 multi-organ protection 2029:2050 However, comprehensive studies are required to elucidate the other possible mechanisms responsible for producing multi-organ protection during RIPC. 25176179 3 57 theme organs 588:593 arg1 RIPC 572:575 RIPC 572:575 RIPC of various organs to provide multi-organ salvage 572:624 RIPC of various organs to provide multi-organ salvage became a successful approach in numerous species of animals. 25176179 1 58 theme duration 202:209 arg1 ischemia 182:189 ischemia 182:189 ischemia of shorter duration 182:209 Ischemic preconditioning is an intrinsic process in which preconditioning ischemia (ischemia of shorter duration) protects the organs against the subsequent index ischemia (sustained ischemia). 25176179 1 59 theme Ischemic 98:105 arg1 process 139:145 an intrinsic process 126:145 an intrinsic process in which preconditioning ischemia (ischemia of shorter duration) protects the organs against the subsequent index ischemia (sustained ischemia) 126:289 Ischemic preconditioning is an intrinsic process in which preconditioning ischemia (ischemia of shorter duration) protects the organs against the subsequent index ischemia (sustained ischemia). 25176179 1 59 theme Ischemic 98:105 arg1 preconditioning 107:121 Ischemic preconditioning 98:121 Ischemic preconditioning 98:121 Ischemic preconditioning is an intrinsic process in which preconditioning ischemia (ischemia of shorter duration) protects the organs against the subsequent index ischemia (sustained ischemia). 25176179 7 60 theme graft 1389:1393 arg1 repair 1430:1435 abdominal aortic aneurysm repair 1404:1435 abdominal aortic aneurysm repair 1404:1435 The institution of RIPC is beneficial in mitigating myocardial injury in patients undergoing various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery. 25176179 7 60 theme graft 1389:1393 arg1 surgery 1575:1581 elective decompression surgery 1552:1581 elective decompression surgery 1552:1581 The institution of RIPC is beneficial in mitigating myocardial injury in patients undergoing various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery. 25176179 7 60 theme graft 1389:1393 arg1 surgery 1486:1492 heart valve surgery 1474:1492 heart valve surgery 1474:1492 The institution of RIPC is beneficial in mitigating myocardial injury in patients undergoing various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery. 25176179 7 60 theme graft 1389:1393 arg1 surgery 1395:1401 graft surgery 1389:1401 graft surgery 1389:1401 The institution of RIPC is beneficial in mitigating myocardial injury in patients undergoing various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery. 25176179 7 60 theme graft 1389:1393 arg1 transplantation 1535:1549 kidney transplantation 1528:1549 kidney transplantation 1528:1549 The institution of RIPC is beneficial in mitigating myocardial injury in patients undergoing various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery. 25176179 7 60 theme graft 1389:1393 arg1 intervention 1460:1471 percutaneous coronary intervention 1438:1471 percutaneous coronary intervention 1438:1471 The institution of RIPC is beneficial in mitigating myocardial injury in patients undergoing various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery. 25176179 7 60 theme graft 1389:1393 arg1 implantation 1514:1525 drug-eluting stent implantation 1495:1525 drug-eluting stent implantation 1495:1525 The institution of RIPC is beneficial in mitigating myocardial injury in patients undergoing various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery. 25176179 5 61 theme forearm 1050:1056 arg1 ischemic 1058:1065 the forearm ischemic 1046:1065 the forearm ischemic 1046:1065 Clinically, RIPC stimulus is generally delivered by inflating the blood pressure cuff tied on the upper arm 20 mm greater than the systolic blood pressure, rendering the forearm ischemic for 5 min, followed 5 min reperfusion by deflating the cuff. 25176179 8 62 theme autonomous 1809:1818 arg1 factor-1α 1621:1629 hypoxia inducible factor-1α 1603:1629 hypoxia inducible factor-1α (HIF-1α) 1603:1638 The involvement of hypoxia inducible factor-1α (HIF-1α), ATP-sensitive potassium channels, signal transducer and activator of transcription (STAT), matrix metalloproteinases, O-linked β-N-acetylglucosamine (O-GlcNAc) levels, autonomous nervous system in mediating RIPC-induced cardioprotective effects has been explored clinically. 25176179 8 62 theme autonomous 1809:1818 arg1 system 1828:1833 autonomous nervous system 1809:1833 autonomous nervous system 1809:1833 The involvement of hypoxia inducible factor-1α (HIF-1α), ATP-sensitive potassium channels, signal transducer and activator of transcription (STAT), matrix metalloproteinases, O-linked β-N-acetylglucosamine (O-GlcNAc) levels, autonomous nervous system in mediating RIPC-induced cardioprotective effects has been explored clinically. 25176179 5 63 theme blood 946:950 arg1 pressure 952:959 the blood pressure cuff 942:964 the blood pressure cuff tied on the upper arm 20 mm greater than the systolic blood pressure 942:1033 Clinically, RIPC stimulus is generally delivered by inflating the blood pressure cuff tied on the upper arm 20 mm greater than the systolic blood pressure, rendering the forearm ischemic for 5 min, followed 5 min reperfusion by deflating the cuff. 25176179 2 64 theme reperfusion-induced 544:562 arg1 injury 564:569 reperfusion-induced injury 544:569 reperfusion-induced injury 544:569 Remote ischemic preconditioning (RIPC) is an innovative treatment approach in which interspersed cycles of preconditioning ischemia followed by reperfusion to a remote organ (other than target organ) protect the target organ against index ischemia and reperfusion-induced injury. 25176179 4 65 theme RIPC 716:719 arg1 concept 705:711 the concept 701:711 the concept of RIPC 701:719 Consequently, the concept of RIPC evolved in clinical setups, and provided beneficial effects in alleviating ischemia-reperfusion-induced injury in various remote organs, including myocardium. 25176179 1 66 theme intrinsic 129:137 arg1 process 139:145 an intrinsic process 126:145 an intrinsic process in which preconditioning ischemia (ischemia of shorter duration) protects the organs against the subsequent index ischemia (sustained ischemia) 126:289 Ischemic preconditioning is an intrinsic process in which preconditioning ischemia (ischemia of shorter duration) protects the organs against the subsequent index ischemia (sustained ischemia). 25176179 1 66 theme intrinsic 129:137 arg1 preconditioning 107:121 Ischemic preconditioning 98:121 Ischemic preconditioning 98:121 Ischemic preconditioning is an intrinsic process in which preconditioning ischemia (ischemia of shorter duration) protects the organs against the subsequent index ischemia (sustained ischemia). 25176179 2 67 dep organ 460:464 arg1 other 467:471 other 467:471 other 467:471 Remote ischemic preconditioning (RIPC) is an innovative treatment approach in which interspersed cycles of preconditioning ischemia followed by reperfusion to a remote organ (other than target organ) protect the target organ against index ischemia and reperfusion-induced injury. 25176179 8 68 theme cardioprotective 1861:1876 arg1 effects 1878:1884 RIPC-induced cardioprotective effects 1848:1884 RIPC-induced cardioprotective effects 1848:1884 The involvement of hypoxia inducible factor-1α (HIF-1α), ATP-sensitive potassium channels, signal transducer and activator of transcription (STAT), matrix metalloproteinases, O-linked β-N-acetylglucosamine (O-GlcNAc) levels, autonomous nervous system in mediating RIPC-induced cardioprotective effects has been explored clinically. 25176179 5 69 theme upper 978:982 arg1 arm 984:986 the upper arm 974:986 the upper arm 20 mm greater than the systolic blood pressure 974:1033 Clinically, RIPC stimulus is generally delivered by inflating the blood pressure cuff tied on the upper arm 20 mm greater than the systolic blood pressure, rendering the forearm ischemic for 5 min, followed 5 min reperfusion by deflating the cuff. 25176179 2 70 theme target 504:509 arg1 organ 511:515 the target organ 500:515 the target organ 500:515 Remote ischemic preconditioning (RIPC) is an innovative treatment approach in which interspersed cycles of preconditioning ischemia followed by reperfusion to a remote organ (other than target organ) protect the target organ against index ischemia and reperfusion-induced injury. 25176179 5 71 theme min 1089:1091 arg1 reperfusion 1093:1103 5 min reperfusion 1087:1103 5 min reperfusion 1087:1103 Clinically, RIPC stimulus is generally delivered by inflating the blood pressure cuff tied on the upper arm 20 mm greater than the systolic blood pressure, rendering the forearm ischemic for 5 min, followed 5 min reperfusion by deflating the cuff. 25176179 7 72 theme various 1325:1331 arg1 interventions 1342:1354 various surgical interventions 1325:1354 various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery 1325:1581 The institution of RIPC is beneficial in mitigating myocardial injury in patients undergoing various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery. 25176179 7 72 theme various 1325:1331 arg1 artery 1375:1380 coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery 1366:1581 coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery 1366:1581 The institution of RIPC is beneficial in mitigating myocardial injury in patients undergoing various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery. 25176179 4 73 theme beneficial 762:771 arg1 effects 773:779 beneficial effects 762:779 beneficial effects 762:779 Consequently, the concept of RIPC evolved in clinical setups, and provided beneficial effects in alleviating ischemia-reperfusion-induced injury in various remote organs, including myocardium. 25176179 2 74 theme interspersed 376:387 arg1 cycles 389:394 interspersed cycles 376:394 interspersed cycles of preconditioning ischemia followed by reperfusion to a remote organ (other than target organ) 376:490 Remote ischemic preconditioning (RIPC) is an innovative treatment approach in which interspersed cycles of preconditioning ischemia followed by reperfusion to a remote organ (other than target organ) protect the target organ against index ischemia and reperfusion-induced injury. 25176179 5 75 theme cuff 961:964 arg1 pressure 952:959 the blood pressure cuff 942:964 the blood pressure cuff tied on the upper arm 20 mm greater than the systolic blood pressure 942:1033 Clinically, RIPC stimulus is generally delivered by inflating the blood pressure cuff tied on the upper arm 20 mm greater than the systolic blood pressure, rendering the forearm ischemic for 5 min, followed 5 min reperfusion by deflating the cuff. 25176179 1 76 theme sustained 271:279 arg1 ischemia 281:288 sustained ischemia 271:288 sustained ischemia 271:288 Ischemic preconditioning is an intrinsic process in which preconditioning ischemia (ischemia of shorter duration) protects the organs against the subsequent index ischemia (sustained ischemia). 25176179 1 76 theme sustained 271:279 arg1 ischemia 261:268 the subsequent index ischemia 240:268 the subsequent index ischemia (sustained ischemia) 240:289 Ischemic preconditioning is an intrinsic process in which preconditioning ischemia (ischemia of shorter duration) protects the organs against the subsequent index ischemia (sustained ischemia). 25176179 8 77 link O-linked 1759:1766 arg1 O-GlcNAc 1791:1798 O-GlcNAc 1791:1798 O-GlcNAc 1791:1798 The involvement of hypoxia inducible factor-1α (HIF-1α), ATP-sensitive potassium channels, signal transducer and activator of transcription (STAT), matrix metalloproteinases, O-linked β-N-acetylglucosamine (O-GlcNAc) levels, autonomous nervous system in mediating RIPC-induced cardioprotective effects has been explored clinically. 25176179 8 77 link O-linked 1759:1766 arg1 β-N-acetylglucosamine 1768:1788 O-linked β-N-acetylglucosamine 1759:1788 O-linked β-N-acetylglucosamine (O-GlcNAc) levels 1759:1806 The involvement of hypoxia inducible factor-1α (HIF-1α), ATP-sensitive potassium channels, signal transducer and activator of transcription (STAT), matrix metalloproteinases, O-linked β-N-acetylglucosamine (O-GlcNAc) levels, autonomous nervous system in mediating RIPC-induced cardioprotective effects has been explored clinically. 25176179 2 78 theme ischemia 415:422 arg1 cycles 389:394 interspersed cycles 376:394 interspersed cycles of preconditioning ischemia followed by reperfusion to a remote organ (other than target organ) 376:490 Remote ischemic preconditioning (RIPC) is an innovative treatment approach in which interspersed cycles of preconditioning ischemia followed by reperfusion to a remote organ (other than target organ) protect the target organ against index ischemia and reperfusion-induced injury. 25176179 0 79 theme clinical 31:38 arg1 settings 40:47 clinical settings 31:47 clinical settings 31:47 RIPC for multiorgan salvage in clinical settings: evolution of concept, evidences and mechanisms. 25176179 5 80 theme blood 1020:1024 arg1 pressure 1026:1033 the systolic blood pressure 1007:1033 the systolic blood pressure 1007:1033 Clinically, RIPC stimulus is generally delivered by inflating the blood pressure cuff tied on the upper arm 20 mm greater than the systolic blood pressure, rendering the forearm ischemic for 5 min, followed 5 min reperfusion by deflating the cuff. 25176179 8 81 theme factor-1α 1621:1629 arg1 involvement 1588:1598 The involvement 1584:1598 The involvement of hypoxia inducible factor-1α (HIF-1α), ATP-sensitive potassium channels, signal transducer and activator of transcription (STAT), matrix metalloproteinases, O-linked β-N-acetylglucosamine (O-GlcNAc) levels, autonomous nervous system in mediating RIPC-induced cardioprotective effects 1584:1884 The involvement of hypoxia inducible factor-1α (HIF-1α), ATP-sensitive potassium channels, signal transducer and activator of transcription (STAT), matrix metalloproteinases, O-linked β-N-acetylglucosamine (O-GlcNAc) levels, autonomous nervous system in mediating RIPC-induced cardioprotective effects has been explored clinically. 25176179 7 82 theme decompression 1561:1573 arg1 surgery 1395:1401 graft surgery 1389:1401 graft surgery 1389:1401 The institution of RIPC is beneficial in mitigating myocardial injury in patients undergoing various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery. 25176179 7 82 theme decompression 1561:1573 arg1 surgery 1575:1581 elective decompression surgery 1552:1581 elective decompression surgery 1552:1581 The institution of RIPC is beneficial in mitigating myocardial injury in patients undergoing various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery. 25176179 2 83 theme remote 453:458 arg1 organ 460:464 a remote organ 451:464 a remote organ (other than target organ) 451:490 Remote ischemic preconditioning (RIPC) is an innovative treatment approach in which interspersed cycles of preconditioning ischemia followed by reperfusion to a remote organ (other than target organ) protect the target organ against index ischemia and reperfusion-induced injury. 25176179 4 84 theme remote 843:848 arg1 myocardium 868:877 myocardium 868:877 myocardium 868:877 Consequently, the concept of RIPC evolved in clinical setups, and provided beneficial effects in alleviating ischemia-reperfusion-induced injury in various remote organs, including myocardium. 25176179 4 84 theme remote 843:848 arg1 organs 850:855 various remote organs 835:855 various remote organs 835:855 Consequently, the concept of RIPC evolved in clinical setups, and provided beneficial effects in alleviating ischemia-reperfusion-induced injury in various remote organs, including myocardium. 25176179 0 85 dep RIPC 0:3 arg1 evolution 50:58 evolution 50:58 RIPC for multiorgan salvage in clinical settings: evolution of concept, evidences and mechanisms. 0:96 RIPC for multiorgan salvage in clinical settings: evolution of concept, evidences and mechanisms. 25176179 5 86 theme greater 994:1000 arg1 arm 984:986 the upper arm 974:986 the upper arm 20 mm greater than the systolic blood pressure 974:1033 Clinically, RIPC stimulus is generally delivered by inflating the blood pressure cuff tied on the upper arm 20 mm greater than the systolic blood pressure, rendering the forearm ischemic for 5 min, followed 5 min reperfusion by deflating the cuff. 25176179 7 87 theme RIPC 1251:1254 arg1 institution 1236:1246 The institution 1232:1246 The institution of RIPC 1232:1254 The institution of RIPC is beneficial in mitigating myocardial injury in patients undergoing various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery. 25176179 7 87 theme RIPC 1251:1254 arg1 beneficial 1259:1268 beneficial 1259:1268 beneficial 1259:1268 The institution of RIPC is beneficial in mitigating myocardial injury in patients undergoing various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery. 25176179 9 88 theme comprehensive 1925:1937 arg1 studies 1939:1945 comprehensive studies 1925:1945 comprehensive studies 1925:1945 However, comprehensive studies are required to elucidate the other possible mechanisms responsible for producing multi-organ protection during RIPC. 25176179 3 89 theme numerous 658:665 arg1 species 667:673 numerous species 658:673 numerous species of animals 658:684 RIPC of various organs to provide multi-organ salvage became a successful approach in numerous species of animals. 25176179 8 90 theme transcription 1710:1722 arg1 STAT 1725:1728 STAT 1725:1728 STAT 1725:1728 The involvement of hypoxia inducible factor-1α (HIF-1α), ATP-sensitive potassium channels, signal transducer and activator of transcription (STAT), matrix metalloproteinases, O-linked β-N-acetylglucosamine (O-GlcNAc) levels, autonomous nervous system in mediating RIPC-induced cardioprotective effects has been explored clinically. 25176179 8 90 theme transcription 1710:1722 arg1 factor-1α 1621:1629 hypoxia inducible factor-1α 1603:1629 hypoxia inducible factor-1α (HIF-1α) 1603:1638 The involvement of hypoxia inducible factor-1α (HIF-1α), ATP-sensitive potassium channels, signal transducer and activator of transcription (STAT), matrix metalloproteinases, O-linked β-N-acetylglucosamine (O-GlcNAc) levels, autonomous nervous system in mediating RIPC-induced cardioprotective effects has been explored clinically. 25176179 8 90 theme transcription 1710:1722 arg1 activator 1697:1705 activator 1697:1705 activator of transcription 1697:1722 The involvement of hypoxia inducible factor-1α (HIF-1α), ATP-sensitive potassium channels, signal transducer and activator of transcription (STAT), matrix metalloproteinases, O-linked β-N-acetylglucosamine (O-GlcNAc) levels, autonomous nervous system in mediating RIPC-induced cardioprotective effects has been explored clinically. 25176179 8 90 theme transcription 1710:1722 arg1 transducer 1682:1691 signal transducer 1675:1691 signal transducer 1675:1691 The involvement of hypoxia inducible factor-1α (HIF-1α), ATP-sensitive potassium channels, signal transducer and activator of transcription (STAT), matrix metalloproteinases, O-linked β-N-acetylglucosamine (O-GlcNAc) levels, autonomous nervous system in mediating RIPC-induced cardioprotective effects has been explored clinically. 25176179 7 91 theme kidney 1528:1533 arg1 transplantation 1535:1549 kidney transplantation 1528:1549 kidney transplantation 1528:1549 The institution of RIPC is beneficial in mitigating myocardial injury in patients undergoing various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery. 25176179 7 91 theme kidney 1528:1533 arg1 surgery 1395:1401 graft surgery 1389:1401 graft surgery 1389:1401 The institution of RIPC is beneficial in mitigating myocardial injury in patients undergoing various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery. 25176179 8 92 theme potassium 1655:1663 arg1 factor-1α 1621:1629 hypoxia inducible factor-1α 1603:1629 hypoxia inducible factor-1α (HIF-1α) 1603:1638 The involvement of hypoxia inducible factor-1α (HIF-1α), ATP-sensitive potassium channels, signal transducer and activator of transcription (STAT), matrix metalloproteinases, O-linked β-N-acetylglucosamine (O-GlcNAc) levels, autonomous nervous system in mediating RIPC-induced cardioprotective effects has been explored clinically. 25176179 8 92 theme potassium 1655:1663 arg1 channels 1665:1672 ATP-sensitive potassium channels 1641:1672 ATP-sensitive potassium channels 1641:1672 The involvement of hypoxia inducible factor-1α (HIF-1α), ATP-sensitive potassium channels, signal transducer and activator of transcription (STAT), matrix metalloproteinases, O-linked β-N-acetylglucosamine (O-GlcNAc) levels, autonomous nervous system in mediating RIPC-induced cardioprotective effects has been explored clinically. 25176179 4 93 theme ischemia-reperfusion-induced 796:823 arg1 injury 825:830 ischemia-reperfusion-induced injury 796:830 ischemia-reperfusion-induced injury in various remote organs, including myocardium 796:877 Consequently, the concept of RIPC evolved in clinical setups, and provided beneficial effects in alleviating ischemia-reperfusion-induced injury in various remote organs, including myocardium. 25176179 2 94 theme treatment 348:356 arg1 preconditioning 308:322 Remote ischemic preconditioning 292:322 Remote ischemic preconditioning (RIPC) 292:329 Remote ischemic preconditioning (RIPC) is an innovative treatment approach in which interspersed cycles of preconditioning ischemia followed by reperfusion to a remote organ (other than target organ) protect the target organ against index ischemia and reperfusion-induced injury. 25176179 2 94 theme treatment 348:356 arg1 approach 358:365 an innovative treatment approach 334:365 an innovative treatment approach in which interspersed cycles of preconditioning ischemia followed by reperfusion to a remote organ (other than target organ) protect the target organ against index ischemia and reperfusion-induced injury 334:569 Remote ischemic preconditioning (RIPC) is an innovative treatment approach in which interspersed cycles of preconditioning ischemia followed by reperfusion to a remote organ (other than target organ) protect the target organ against index ischemia and reperfusion-induced injury. 25835259 0 0 theme Diabetic 98:105 arg1 Retinopathy 107:117 Streptozotocin-induced Diabetic Retinopathy 75:117 Streptozotocin-induced Diabetic Retinopathy 75:117 Increased O-GlcNAcylation of NF-κB Enhances Retinal Ganglion Cell Death in Streptozotocin-induced Diabetic Retinopathy. 25835259 1 1 theme hexoxamine 180:189 arg1 pathway 204:210 the hexoxamine biosynthetic pathway 176:210 the hexoxamine biosynthetic pathway 176:210 PURPOSE Hyperglycemia results in increased flux through the hexoxamine biosynthetic pathway. 25835259 6 2 dep NeuN 1082:1085 arg1 cells 1194:1198 nick-end labeling-positive cells 1167:1198 nick-end labeling-positive cells 1167:1198 OGT colocalized with NeuN, a RGC-specific marker, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive cells in the ganglion cell layer of diabetic retinas. 25835259 0 3 theme Streptozotocin-induced 75:96 arg1 Retinopathy 107:117 Streptozotocin-induced Diabetic Retinopathy 75:117 Streptozotocin-induced Diabetic Retinopathy 75:117 Increased O-GlcNAcylation of NF-κB Enhances Retinal Ganglion Cell Death in Streptozotocin-induced Diabetic Retinopathy. 25835259 2 4 theme cells 399:403 arg1 apoptosis 369:377 apoptosis 369:377 apoptosis of retinal ganglion cells (RGCs) in diabetic retinopathy (DR) 369:439 We examined whether hyperglycemia increases O-GlcNAcylation in the diabetic retina and whether elevated O-GlcNAcylation of nuclear factor (NF)-κB increases apoptosis of retinal ganglion cells (RGCs) in diabetic retinopathy (DR). 25835259 6 5 theme labeling-positive 1176:1192 arg1 cells 1194:1198 nick-end labeling-positive cells 1167:1198 nick-end labeling-positive cells 1167:1198 OGT colocalized with NeuN, a RGC-specific marker, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive cells in the ganglion cell layer of diabetic retinas. 25835259 8 6 theme subunit 1507:1513 arg1 O-GlcNAcylation 1480:1494 O-GlcNAcylation 1480:1494 O-GlcNAcylation of the p65 subunit of NF-κB 1480:1522 CONCLUSION The present data suggest that hyperglycemia increases O-GlcNAcylation in DR and that O-GlcNAcylation of the p65 subunit of NF-κB is involved in hyperglycemia-induced NF-κB activation and RGC death in DR. 25835259 2 7 from apoptosis 369:377 arg1 retinopathy 424:434 diabetic retinopathy 415:434 diabetic retinopathy (DR) 415:439 We examined whether hyperglycemia increases O-GlcNAcylation in the diabetic retina and whether elevated O-GlcNAcylation of nuclear factor (NF)-κB increases apoptosis of retinal ganglion cells (RGCs) in diabetic retinopathy (DR). 25835259 2 7 from apoptosis 369:377 arg1 DR 437:438 DR 437:438 DR 437:438 We examined whether hyperglycemia increases O-GlcNAcylation in the diabetic retina and whether elevated O-GlcNAcylation of nuclear factor (NF)-κB increases apoptosis of retinal ganglion cells (RGCs) in diabetic retinopathy (DR). 25835259 5 8 theme diabetic 1019:1026 arg1 retinas 1028:1034 diabetic retinas 1019:1034 diabetic retinas 1019:1034 Immunoprecipitations were performed to investigate whether O-GlcNAcylation of NF-κB led to its activation and RGC death in DR. RESULTS The expression levels of O-GlcNAcylated proteins and OGT were markedly higher in diabetic retinas than in control retinas. 25835259 7 9 theme diabetic 1342:1349 arg1 retinas 1351:1357 diabetic retinas 1342:1357 diabetic retinas 1342:1357 The p65 subunit of NF-κB was O-GlcNAcylated and the level of O-GlcNAcylated p65 was higher in diabetic retinas than in control retinas. 25835259 6 10 theme retinas 1239:1245 arg1 layer 1221:1225 the ganglion cell layer 1203:1225 the ganglion cell layer of diabetic retinas 1203:1245 OGT colocalized with NeuN, a RGC-specific marker, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive cells in the ganglion cell layer of diabetic retinas. 25835259 2 11 theme factor 344:349 arg1 -κB 355:357 nuclear factor (NF)-κB 336:357 nuclear factor (NF)-κB 336:357 We examined whether hyperglycemia increases O-GlcNAcylation in the diabetic retina and whether elevated O-GlcNAcylation of nuclear factor (NF)-κB increases apoptosis of retinal ganglion cells (RGCs) in diabetic retinopathy (DR). 25835259 4 12 theme expression 627:636 arg1 levels 638:643 expression levels 627:643 expression levels of O-GlcNAcylated proteins, O-linked N-acetylglucosamine transferase (OGT), β-d-N-acetylglucosaminidase and NF-κB, 627:758 All mice were killed 2 months after injections and expression levels of O-GlcNAcylated proteins, O-linked N-acetylglucosamine transferase (OGT), β-d-N-acetylglucosaminidase and NF-κB, and the extent of RGC death were examined. 25835259 7 13 theme NF-κB 1267:1271 arg1 O-GlcNAcylated 1277:1290 O-GlcNAcylated 1277:1290 O-GlcNAcylated 1277:1290 The p65 subunit of NF-κB was O-GlcNAcylated and the level of O-GlcNAcylated p65 was higher in diabetic retinas than in control retinas. 25835259 7 13 theme NF-κB 1267:1271 arg1 subunit 1256:1262 The p65 subunit 1248:1262 The p65 subunit of NF-κB 1248:1271 The p65 subunit of NF-κB was O-GlcNAcylated and the level of O-GlcNAcylated p65 was higher in diabetic retinas than in control retinas. 25835259 3 14 theme consecutive 509:519 arg1 injections 537:546 five consecutive intraperitoneal injections 504:546 five consecutive intraperitoneal injections of 55 mg/kg streptozotocin 504:573 MATERIALS AND METHODS Diabetes was induced in C57BL/6 mice by five consecutive intraperitoneal injections of 55 mg/kg streptozotocin. 25835259 7 15 theme p65 1252:1254 arg1 O-GlcNAcylated 1277:1290 O-GlcNAcylated 1277:1290 O-GlcNAcylated 1277:1290 The p65 subunit of NF-κB was O-GlcNAcylated and the level of O-GlcNAcylated p65 was higher in diabetic retinas than in control retinas. 25835259 7 15 theme p65 1252:1254 arg1 subunit 1256:1262 The p65 subunit 1248:1262 The p65 subunit of NF-κB 1248:1271 The p65 subunit of NF-κB was O-GlcNAcylated and the level of O-GlcNAcylated p65 was higher in diabetic retinas than in control retinas. 25835259 2 16 theme nuclear 336:342 arg1 factor 344:349 nuclear factor 336:349 nuclear factor (NF)-κB 336:357 We examined whether hyperglycemia increases O-GlcNAcylation in the diabetic retina and whether elevated O-GlcNAcylation of nuclear factor (NF)-κB increases apoptosis of retinal ganglion cells (RGCs) in diabetic retinopathy (DR). 25835259 2 16 theme nuclear 336:342 arg1 NF 352:353 NF 352:353 NF 352:353 We examined whether hyperglycemia increases O-GlcNAcylation in the diabetic retina and whether elevated O-GlcNAcylation of nuclear factor (NF)-κB increases apoptosis of retinal ganglion cells (RGCs) in diabetic retinopathy (DR). 25835259 6 17 theme deoxynucleotidyl 1124:1139 arg1 dUTP 1162:1165 terminal deoxynucleotidyl transferase-mediated dUTP 1115:1165 terminal deoxynucleotidyl transferase-mediated dUTP 1115:1165 OGT colocalized with NeuN, a RGC-specific marker, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive cells in the ganglion cell layer of diabetic retinas. 25835259 8 18 from activation 1567:1576 arg1 DR 1595:1596 DR 1595:1596 DR 1595:1596 CONCLUSION The present data suggest that hyperglycemia increases O-GlcNAcylation in DR and that O-GlcNAcylation of the p65 subunit of NF-κB is involved in hyperglycemia-induced NF-κB activation and RGC death in DR. 25835259 5 19 theme O-GlcNAcylated 963:976 arg1 proteins 978:985 O-GlcNAcylated proteins 963:985 O-GlcNAcylated proteins 963:985 Immunoprecipitations were performed to investigate whether O-GlcNAcylation of NF-κB led to its activation and RGC death in DR. RESULTS The expression levels of O-GlcNAcylated proteins and OGT were markedly higher in diabetic retinas than in control retinas. 25835259 6 20 theme ganglion 1207:1214 arg1 layer 1221:1225 the ganglion cell layer 1203:1225 the ganglion cell layer of diabetic retinas 1203:1245 OGT colocalized with NeuN, a RGC-specific marker, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive cells in the ganglion cell layer of diabetic retinas. 25835259 5 21 theme control 1044:1050 arg1 retinas 1052:1058 control retinas 1044:1058 control retinas 1044:1058 Immunoprecipitations were performed to investigate whether O-GlcNAcylation of NF-κB led to its activation and RGC death in DR. RESULTS The expression levels of O-GlcNAcylated proteins and OGT were markedly higher in diabetic retinas than in control retinas. 25835259 6 22 theme nick-end 1167:1174 arg1 cells 1194:1198 nick-end labeling-positive cells 1167:1198 nick-end labeling-positive cells 1167:1198 OGT colocalized with NeuN, a RGC-specific marker, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive cells in the ganglion cell layer of diabetic retinas. 25835259 6 23 theme transferase-mediated 1141:1160 arg1 dUTP 1162:1165 terminal deoxynucleotidyl transferase-mediated dUTP 1115:1165 terminal deoxynucleotidyl transferase-mediated dUTP 1115:1165 OGT colocalized with NeuN, a RGC-specific marker, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive cells in the ganglion cell layer of diabetic retinas. 25835259 5 24 theme NF-κB 881:885 arg1 O-GlcNAcylation 862:876 O-GlcNAcylation 862:876 O-GlcNAcylation of NF-κB 862:885 Immunoprecipitations were performed to investigate whether O-GlcNAcylation of NF-κB led to its activation and RGC death in DR. RESULTS The expression levels of O-GlcNAcylated proteins and OGT were markedly higher in diabetic retinas than in control retinas. 25835259 7 25 theme control 1367:1373 arg1 retinas 1375:1381 control retinas 1367:1381 control retinas 1367:1381 The p65 subunit of NF-κB was O-GlcNAcylated and the level of O-GlcNAcylated p65 was higher in diabetic retinas than in control retinas. 25835259 2 26 theme diabetic 415:422 arg1 retinopathy 424:434 diabetic retinopathy 415:434 diabetic retinopathy (DR) 415:439 We examined whether hyperglycemia increases O-GlcNAcylation in the diabetic retina and whether elevated O-GlcNAcylation of nuclear factor (NF)-κB increases apoptosis of retinal ganglion cells (RGCs) in diabetic retinopathy (DR). 25835259 2 26 theme diabetic 415:422 arg1 DR 437:438 DR 437:438 DR 437:438 We examined whether hyperglycemia increases O-GlcNAcylation in the diabetic retina and whether elevated O-GlcNAcylation of nuclear factor (NF)-κB increases apoptosis of retinal ganglion cells (RGCs) in diabetic retinopathy (DR). 25835259 0 27 theme Increased 0:8 arg1 O-GlcNAcylation 10:24 Increased O-GlcNAcylation 0:24 Increased O-GlcNAcylation of NF-κB 0:33 Increased O-GlcNAcylation of NF-κB Enhances Retinal Ganglion Cell Death in Streptozotocin-induced Diabetic Retinopathy. 25835259 2 28 theme -κB 355:357 arg1 O-GlcNAcylation 317:331 elevated O-GlcNAcylation 308:331 elevated O-GlcNAcylation of nuclear factor (NF)-κB 308:357 We examined whether hyperglycemia increases O-GlcNAcylation in the diabetic retina and whether elevated O-GlcNAcylation of nuclear factor (NF)-κB increases apoptosis of retinal ganglion cells (RGCs) in diabetic retinopathy (DR). 25835259 3 29 theme METHODS 456:462 arg1 Diabetes 464:471 MATERIALS AND METHODS Diabetes 442:471 MATERIALS AND METHODS Diabetes 442:471 MATERIALS AND METHODS Diabetes was induced in C57BL/6 mice by five consecutive intraperitoneal injections of 55 mg/kg streptozotocin. 25835259 0 30 theme NF-κB 29:33 arg1 O-GlcNAcylation 10:24 Increased O-GlcNAcylation 0:24 Increased O-GlcNAcylation of NF-κB 0:33 Increased O-GlcNAcylation of NF-κB Enhances Retinal Ganglion Cell Death in Streptozotocin-induced Diabetic Retinopathy. 25835259 8 31 theme hyperglycemia-induced 1539:1559 arg1 activation 1567:1576 hyperglycemia-induced NF-κB activation 1539:1576 hyperglycemia-induced NF-κB activation 1539:1576 CONCLUSION The present data suggest that hyperglycemia increases O-GlcNAcylation in DR and that O-GlcNAcylation of the p65 subunit of NF-κB is involved in hyperglycemia-induced NF-κB activation and RGC death in DR. 25835259 1 32 theme PURPOSE 120:126 arg1 Hyperglycemia 128:140 PURPOSE Hyperglycemia 120:140 PURPOSE Hyperglycemia 120:140 PURPOSE Hyperglycemia results in increased flux through the hexoxamine biosynthetic pathway. 25835259 3 33 theme C57BL/6 488:494 arg1 mice 496:499 C57BL/6 mice 488:499 C57BL/6 mice 488:499 MATERIALS AND METHODS Diabetes was induced in C57BL/6 mice by five consecutive intraperitoneal injections of 55 mg/kg streptozotocin. 25835259 4 34 theme death 782:786 arg1 extent 768:773 the extent 764:773 the extent of RGC death 764:786 All mice were killed 2 months after injections and expression levels of O-GlcNAcylated proteins, O-linked N-acetylglucosamine transferase (OGT), β-d-N-acetylglucosaminidase and NF-κB, and the extent of RGC death were examined. 25835259 4 34 theme death 782:786 arg1 levels 638:643 expression levels 627:643 expression levels of O-GlcNAcylated proteins, O-linked N-acetylglucosamine transferase (OGT), β-d-N-acetylglucosaminidase and NF-κB, 627:758 All mice were killed 2 months after injections and expression levels of O-GlcNAcylated proteins, O-linked N-acetylglucosamine transferase (OGT), β-d-N-acetylglucosaminidase and NF-κB, and the extent of RGC death were examined. 25835259 1 35 theme biosynthetic 191:202 arg1 pathway 204:210 the hexoxamine biosynthetic pathway 176:210 the hexoxamine biosynthetic pathway 176:210 PURPOSE Hyperglycemia results in increased flux through the hexoxamine biosynthetic pathway. 25835259 8 36 gly O-GlcNAcylation 1480:1494 arg1 activation 1567:1576 hyperglycemia-induced NF-κB activation 1539:1576 hyperglycemia-induced NF-κB activation 1539:1576 CONCLUSION The present data suggest that hyperglycemia increases O-GlcNAcylation in DR and that O-GlcNAcylation of the p65 subunit of NF-κB is involved in hyperglycemia-induced NF-κB activation and RGC death in DR. 25835259 8 36 gly O-GlcNAcylation 1480:1494 arg1 death 1586:1590 RGC death 1582:1590 RGC death in DR 1582:1596 CONCLUSION The present data suggest that hyperglycemia increases O-GlcNAcylation in DR and that O-GlcNAcylation of the p65 subunit of NF-κB is involved in hyperglycemia-induced NF-κB activation and RGC death in DR. 25835259 4 37 theme O-linked 673:680 arg1 transferase 702:712 O-linked N-acetylglucosamine transferase 673:712 O-linked N-acetylglucosamine transferase (OGT) 673:718 All mice were killed 2 months after injections and expression levels of O-GlcNAcylated proteins, O-linked N-acetylglucosamine transferase (OGT), β-d-N-acetylglucosaminidase and NF-κB, and the extent of RGC death were examined. 25835259 4 37 theme O-linked 673:680 arg1 proteins 663:670 O-GlcNAcylated proteins 648:670 O-GlcNAcylated proteins 648:670 All mice were killed 2 months after injections and expression levels of O-GlcNAcylated proteins, O-linked N-acetylglucosamine transferase (OGT), β-d-N-acetylglucosaminidase and NF-κB, and the extent of RGC death were examined. 25835259 4 37 theme O-linked 673:680 arg1 OGT 715:717 OGT 715:717 OGT 715:717 All mice were killed 2 months after injections and expression levels of O-GlcNAcylated proteins, O-linked N-acetylglucosamine transferase (OGT), β-d-N-acetylglucosaminidase and NF-κB, and the extent of RGC death were examined. 25835259 0 38 theme Retinal 44:50 arg1 Death 66:70 Retinal Ganglion Cell Death 44:70 Retinal Ganglion Cell Death in Streptozotocin-induced Diabetic Retinopathy 44:117 Increased O-GlcNAcylation of NF-κB Enhances Retinal Ganglion Cell Death in Streptozotocin-induced Diabetic Retinopathy. 25835259 3 39 theme intraperitoneal 521:535 arg1 injections 537:546 five consecutive intraperitoneal injections 504:546 five consecutive intraperitoneal injections of 55 mg/kg streptozotocin 504:573 MATERIALS AND METHODS Diabetes was induced in C57BL/6 mice by five consecutive intraperitoneal injections of 55 mg/kg streptozotocin. 25835259 6 40 theme cell 1216:1219 arg1 layer 1221:1225 the ganglion cell layer 1203:1225 the ganglion cell layer of diabetic retinas 1203:1245 OGT colocalized with NeuN, a RGC-specific marker, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive cells in the ganglion cell layer of diabetic retinas. 25835259 8 41 theme present 1399:1405 arg1 data 1407:1410 The present data 1395:1410 The present data 1395:1410 CONCLUSION The present data suggest that hyperglycemia increases O-GlcNAcylation in DR and that O-GlcNAcylation of the p65 subunit of NF-κB is involved in hyperglycemia-induced NF-κB activation and RGC death in DR. 25835259 6 42 theme terminal 1115:1122 arg1 dUTP 1162:1165 terminal deoxynucleotidyl transferase-mediated dUTP 1115:1165 terminal deoxynucleotidyl transferase-mediated dUTP 1115:1165 OGT colocalized with NeuN, a RGC-specific marker, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive cells in the ganglion cell layer of diabetic retinas. 25835259 5 43 theme RGC 913:915 arg1 death 917:921 RGC death 913:921 RGC death in DR. RESULTS The expression levels of O-GlcNAcylated proteins 913:985 Immunoprecipitations were performed to investigate whether O-GlcNAcylation of NF-κB led to its activation and RGC death in DR. RESULTS The expression levels of O-GlcNAcylated proteins and OGT were markedly higher in diabetic retinas than in control retinas. 25835259 3 44 theme MATERIALS 442:450 arg1 Diabetes 464:471 MATERIALS AND METHODS Diabetes 442:471 MATERIALS AND METHODS Diabetes 442:471 MATERIALS AND METHODS Diabetes was induced in C57BL/6 mice by five consecutive intraperitoneal injections of 55 mg/kg streptozotocin. 25835259 8 45 theme NF-κB 1561:1565 arg1 activation 1567:1576 hyperglycemia-induced NF-κB activation 1539:1576 hyperglycemia-induced NF-κB activation 1539:1576 CONCLUSION The present data suggest that hyperglycemia increases O-GlcNAcylation in DR and that O-GlcNAcylation of the p65 subunit of NF-κB is involved in hyperglycemia-induced NF-κB activation and RGC death in DR. 25835259 2 46 theme diabetic 280:287 arg1 retina 289:294 the diabetic retina 276:294 the diabetic retina 276:294 We examined whether hyperglycemia increases O-GlcNAcylation in the diabetic retina and whether elevated O-GlcNAcylation of nuclear factor (NF)-κB increases apoptosis of retinal ganglion cells (RGCs) in diabetic retinopathy (DR). 25835259 6 47 theme RGC-specific 1090:1101 arg1 NeuN 1082:1085 NeuN 1082:1085 NeuN 1082:1085 OGT colocalized with NeuN, a RGC-specific marker, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive cells in the ganglion cell layer of diabetic retinas. 25835259 6 47 theme RGC-specific 1090:1101 arg1 marker 1103:1108 a RGC-specific marker 1088:1108 a RGC-specific marker 1088:1108 OGT colocalized with NeuN, a RGC-specific marker, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive cells in the ganglion cell layer of diabetic retinas. 25835259 0 48 theme Cell 61:64 arg1 Death 66:70 Retinal Ganglion Cell Death 44:70 Retinal Ganglion Cell Death in Streptozotocin-induced Diabetic Retinopathy 44:117 Increased O-GlcNAcylation of NF-κB Enhances Retinal Ganglion Cell Death in Streptozotocin-induced Diabetic Retinopathy. 25835259 5 49 theme expression 942:951 arg1 levels 953:958 The expression levels 938:958 The expression levels of O-GlcNAcylated proteins 938:985 Immunoprecipitations were performed to investigate whether O-GlcNAcylation of NF-κB led to its activation and RGC death in DR. RESULTS The expression levels of O-GlcNAcylated proteins and OGT were markedly higher in diabetic retinas than in control retinas. 25835259 8 50 from death 1586:1590 arg1 DR 1595:1596 DR 1595:1596 DR 1595:1596 CONCLUSION The present data suggest that hyperglycemia increases O-GlcNAcylation in DR and that O-GlcNAcylation of the p65 subunit of NF-κB is involved in hyperglycemia-induced NF-κB activation and RGC death in DR. 25835259 0 51 from Death 66:70 arg1 Retinopathy 107:117 Streptozotocin-induced Diabetic Retinopathy 75:117 Streptozotocin-induced Diabetic Retinopathy 75:117 Increased O-GlcNAcylation of NF-κB Enhances Retinal Ganglion Cell Death in Streptozotocin-induced Diabetic Retinopathy. 25835259 8 52 theme p65 1503:1505 arg1 subunit 1507:1513 the p65 subunit 1499:1513 the p65 subunit of NF-κB 1499:1522 CONCLUSION The present data suggest that hyperglycemia increases O-GlcNAcylation in DR and that O-GlcNAcylation of the p65 subunit of NF-κB is involved in hyperglycemia-induced NF-κB activation and RGC death in DR. 25835259 5 53 from death 917:921 arg1 DR. 926:928 DR. 926:928 DR. 926:928 Immunoprecipitations were performed to investigate whether O-GlcNAcylation of NF-κB led to its activation and RGC death in DR. RESULTS The expression levels of O-GlcNAcylated proteins and OGT were markedly higher in diabetic retinas than in control retinas. 25835259 2 54 theme ganglion 390:397 arg1 RGCs 406:409 RGCs 406:409 RGCs 406:409 We examined whether hyperglycemia increases O-GlcNAcylation in the diabetic retina and whether elevated O-GlcNAcylation of nuclear factor (NF)-κB increases apoptosis of retinal ganglion cells (RGCs) in diabetic retinopathy (DR). 25835259 2 54 theme ganglion 390:397 arg1 cells 399:403 retinal ganglion cells 382:403 retinal ganglion cells (RGCs) 382:410 We examined whether hyperglycemia increases O-GlcNAcylation in the diabetic retina and whether elevated O-GlcNAcylation of nuclear factor (NF)-κB increases apoptosis of retinal ganglion cells (RGCs) in diabetic retinopathy (DR). 25835259 0 55 theme Ganglion 52:59 arg1 Death 66:70 Retinal Ganglion Cell Death 44:70 Retinal Ganglion Cell Death in Streptozotocin-induced Diabetic Retinopathy 44:117 Increased O-GlcNAcylation of NF-κB Enhances Retinal Ganglion Cell Death in Streptozotocin-induced Diabetic Retinopathy. 25835259 5 56 dep DR. 926:928 arg1 RESULTS 930:936 RESULTS 930:936 RESULTS The expression levels of O-GlcNAcylated proteins 930:985 Immunoprecipitations were performed to investigate whether O-GlcNAcylation of NF-κB led to its activation and RGC death in DR. RESULTS The expression levels of O-GlcNAcylated proteins and OGT were markedly higher in diabetic retinas than in control retinas. 25835259 5 57 from activation 898:907 arg1 DR. 926:928 DR. 926:928 DR. 926:928 Immunoprecipitations were performed to investigate whether O-GlcNAcylation of NF-κB led to its activation and RGC death in DR. RESULTS The expression levels of O-GlcNAcylated proteins and OGT were markedly higher in diabetic retinas than in control retinas. 25835259 2 58 theme retinal 382:388 arg1 RGCs 406:409 RGCs 406:409 RGCs 406:409 We examined whether hyperglycemia increases O-GlcNAcylation in the diabetic retina and whether elevated O-GlcNAcylation of nuclear factor (NF)-κB increases apoptosis of retinal ganglion cells (RGCs) in diabetic retinopathy (DR). 25835259 2 58 theme retinal 382:388 arg1 cells 399:403 retinal ganglion cells 382:403 retinal ganglion cells (RGCs) 382:410 We examined whether hyperglycemia increases O-GlcNAcylation in the diabetic retina and whether elevated O-GlcNAcylation of nuclear factor (NF)-κB increases apoptosis of retinal ganglion cells (RGCs) in diabetic retinopathy (DR). 25835259 8 59 from O-GlcNAcylation 1449:1463 arg1 DR 1468:1469 DR 1468:1469 DR 1468:1469 CONCLUSION The present data suggest that hyperglycemia increases O-GlcNAcylation in DR and that O-GlcNAcylation of the p65 subunit of NF-κB is involved in hyperglycemia-induced NF-κB activation and RGC death in DR. 25835259 8 60 theme NF-κB 1518:1522 arg1 subunit 1507:1513 the p65 subunit 1499:1513 the p65 subunit of NF-κB 1499:1522 CONCLUSION The present data suggest that hyperglycemia increases O-GlcNAcylation in DR and that O-GlcNAcylation of the p65 subunit of NF-κB is involved in hyperglycemia-induced NF-κB activation and RGC death in DR. 25835259 8 61 dep CONCLUSION 1384:1393 arg1 suggest 1412:1418 suggest 1412:1418 suggest that hyperglycemia increases O-GlcNAcylation in DR and that O-GlcNAcylation of the p65 subunit of NF-κB is involved in hyperglycemia-induced NF-κB activation and RGC death in DR 1412:1596 CONCLUSION The present data suggest that hyperglycemia increases O-GlcNAcylation in DR and that O-GlcNAcylation of the p65 subunit of NF-κB is involved in hyperglycemia-induced NF-κB activation and RGC death in DR. 25835259 1 62 theme increased 153:161 arg1 flux 163:166 increased flux 153:166 increased flux through the hexoxamine biosynthetic pathway 153:210 PURPOSE Hyperglycemia results in increased flux through the hexoxamine biosynthetic pathway. 25835259 6 63 theme diabetic 1230:1237 arg1 retinas 1239:1245 diabetic retinas 1230:1245 diabetic retinas 1230:1245 OGT colocalized with NeuN, a RGC-specific marker, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive cells in the ganglion cell layer of diabetic retinas. 25835259 4 64 theme O-GlcNAcylated 648:661 arg1 transferase 702:712 O-linked N-acetylglucosamine transferase 673:712 O-linked N-acetylglucosamine transferase (OGT) 673:718 All mice were killed 2 months after injections and expression levels of O-GlcNAcylated proteins, O-linked N-acetylglucosamine transferase (OGT), β-d-N-acetylglucosaminidase and NF-κB, and the extent of RGC death were examined. 25835259 4 64 theme O-GlcNAcylated 648:661 arg1 proteins 663:670 O-GlcNAcylated proteins 648:670 O-GlcNAcylated proteins 648:670 All mice were killed 2 months after injections and expression levels of O-GlcNAcylated proteins, O-linked N-acetylglucosamine transferase (OGT), β-d-N-acetylglucosaminidase and NF-κB, and the extent of RGC death were examined. 25835259 4 64 theme O-GlcNAcylated 648:661 arg1 NF-κB 753:757 NF-κB 753:757 NF-κB 753:757 All mice were killed 2 months after injections and expression levels of O-GlcNAcylated proteins, O-linked N-acetylglucosamine transferase (OGT), β-d-N-acetylglucosaminidase and NF-κB, and the extent of RGC death were examined. 25835259 4 64 theme O-GlcNAcylated 648:661 arg1 β-d-N-acetylglucosaminidase 721:747 β-d-N-acetylglucosaminidase 721:747 β-d-N-acetylglucosaminidase 721:747 All mice were killed 2 months after injections and expression levels of O-GlcNAcylated proteins, O-linked N-acetylglucosamine transferase (OGT), β-d-N-acetylglucosaminidase and NF-κB, and the extent of RGC death were examined. 25835259 5 65 theme proteins 978:985 arg1 levels 953:958 The expression levels 938:958 The expression levels of O-GlcNAcylated proteins 938:985 Immunoprecipitations were performed to investigate whether O-GlcNAcylation of NF-κB led to its activation and RGC death in DR. RESULTS The expression levels of O-GlcNAcylated proteins and OGT were markedly higher in diabetic retinas than in control retinas. 25835259 2 66 theme elevated 308:315 arg1 O-GlcNAcylation 317:331 elevated O-GlcNAcylation 308:331 elevated O-GlcNAcylation of nuclear factor (NF)-κB 308:357 We examined whether hyperglycemia increases O-GlcNAcylation in the diabetic retina and whether elevated O-GlcNAcylation of nuclear factor (NF)-κB increases apoptosis of retinal ganglion cells (RGCs) in diabetic retinopathy (DR). 25835259 4 67 theme RGC 778:780 arg1 death 782:786 RGC death 778:786 RGC death 778:786 All mice were killed 2 months after injections and expression levels of O-GlcNAcylated proteins, O-linked N-acetylglucosamine transferase (OGT), β-d-N-acetylglucosaminidase and NF-κB, and the extent of RGC death were examined. 25835259 8 68 theme RGC 1582:1584 arg1 death 1586:1590 RGC death 1582:1590 RGC death in DR 1582:1596 CONCLUSION The present data suggest that hyperglycemia increases O-GlcNAcylation in DR and that O-GlcNAcylation of the p65 subunit of NF-κB is involved in hyperglycemia-induced NF-κB activation and RGC death in DR. 25835259 4 69 theme N-acetylglucosamine 682:700 arg1 transferase 702:712 O-linked N-acetylglucosamine transferase 673:712 O-linked N-acetylglucosamine transferase (OGT) 673:718 All mice were killed 2 months after injections and expression levels of O-GlcNAcylated proteins, O-linked N-acetylglucosamine transferase (OGT), β-d-N-acetylglucosaminidase and NF-κB, and the extent of RGC death were examined. 25835259 4 69 theme N-acetylglucosamine 682:700 arg1 proteins 663:670 O-GlcNAcylated proteins 648:670 O-GlcNAcylated proteins 648:670 All mice were killed 2 months after injections and expression levels of O-GlcNAcylated proteins, O-linked N-acetylglucosamine transferase (OGT), β-d-N-acetylglucosaminidase and NF-κB, and the extent of RGC death were examined. 25835259 4 69 theme N-acetylglucosamine 682:700 arg1 OGT 715:717 OGT 715:717 OGT 715:717 All mice were killed 2 months after injections and expression levels of O-GlcNAcylated proteins, O-linked N-acetylglucosamine transferase (OGT), β-d-N-acetylglucosaminidase and NF-κB, and the extent of RGC death were examined. 25835259 3 70 theme 55 mg/kg 551:558 arg1 streptozotocin 560:573 55 mg/kg streptozotocin 551:573 55 mg/kg streptozotocin 551:573 MATERIALS AND METHODS Diabetes was induced in C57BL/6 mice by five consecutive intraperitoneal injections of 55 mg/kg streptozotocin. 25835259 7 71 theme O-GlcNAcylated 1309:1322 arg1 p65 1324:1326 O-GlcNAcylated p65 1309:1326 O-GlcNAcylated p65 1309:1326 The p65 subunit of NF-κB was O-GlcNAcylated and the level of O-GlcNAcylated p65 was higher in diabetic retinas than in control retinas. 25835259 4 72 link O-linked 673:680 arg1 transferase 702:712 O-linked N-acetylglucosamine transferase 673:712 O-linked N-acetylglucosamine transferase (OGT) 673:718 All mice were killed 2 months after injections and expression levels of O-GlcNAcylated proteins, O-linked N-acetylglucosamine transferase (OGT), β-d-N-acetylglucosaminidase and NF-κB, and the extent of RGC death were examined. 25835259 4 72 link O-linked 673:680 arg1 proteins 663:670 O-GlcNAcylated proteins 648:670 O-GlcNAcylated proteins 648:670 All mice were killed 2 months after injections and expression levels of O-GlcNAcylated proteins, O-linked N-acetylglucosamine transferase (OGT), β-d-N-acetylglucosaminidase and NF-κB, and the extent of RGC death were examined. 25835259 4 72 link O-linked 673:680 arg1 OGT 715:717 OGT 715:717 OGT 715:717 All mice were killed 2 months after injections and expression levels of O-GlcNAcylated proteins, O-linked N-acetylglucosamine transferase (OGT), β-d-N-acetylglucosaminidase and NF-κB, and the extent of RGC death were examined. 25835259 3 73 theme streptozotocin 560:573 arg1 injections 537:546 five consecutive intraperitoneal injections 504:546 five consecutive intraperitoneal injections of 55 mg/kg streptozotocin 504:573 MATERIALS AND METHODS Diabetes was induced in C57BL/6 mice by five consecutive intraperitoneal injections of 55 mg/kg streptozotocin. 25835259 7 74 theme p65 1324:1326 arg1 higher 1332:1337 higher 1332:1337 higher 1332:1337 The p65 subunit of NF-κB was O-GlcNAcylated and the level of O-GlcNAcylated p65 was higher in diabetic retinas than in control retinas. 25835259 7 74 theme p65 1324:1326 arg1 level 1300:1304 the level 1296:1304 the level of O-GlcNAcylated p65 1296:1326 The p65 subunit of NF-κB was O-GlcNAcylated and the level of O-GlcNAcylated p65 was higher in diabetic retinas than in control retinas. 25835259 4 75 theme proteins 663:670 arg1 extent 768:773 the extent 764:773 the extent of RGC death 764:786 All mice were killed 2 months after injections and expression levels of O-GlcNAcylated proteins, O-linked N-acetylglucosamine transferase (OGT), β-d-N-acetylglucosaminidase and NF-κB, and the extent of RGC death were examined. 25835259 4 75 theme proteins 663:670 arg1 levels 638:643 expression levels 627:643 expression levels of O-GlcNAcylated proteins, O-linked N-acetylglucosamine transferase (OGT), β-d-N-acetylglucosaminidase and NF-κB, 627:758 All mice were killed 2 months after injections and expression levels of O-GlcNAcylated proteins, O-linked N-acetylglucosamine transferase (OGT), β-d-N-acetylglucosaminidase and NF-κB, and the extent of RGC death were examined. 25315705 7 0 from increases 991:999 arg1 levels 1042:1047 total protein O-GlcNAcylation levels 1012:1047 total protein O-GlcNAcylation levels 1012:1047 Higher levels of mRNA/protein for both OGT and OGA as well as significant increases of 60 % in total protein O-GlcNAcylation levels were noted in SCLC compared with NCLM (p < 0.05). 25315705 10 1 theme p 1524:1524 arg1 tumors 1516:1521 poorly differentiated tumors 1494:1521 poorly differentiated tumors (p < 0.05) 1494:1532 In addition, the highest OGT and OGA protein levels were observed in poorly differentiated tumors (p < 0.05). 25315705 10 1 theme p 1524:1524 arg1 < 1526:1526 p < 0.05 1524:1531 p < 0.05 1524:1531 In addition, the highest OGT and OGA protein levels were observed in poorly differentiated tumors (p < 0.05). 25315705 6 2 theme MGEA5 787:791 arg1 transcripts 793:803 OGT and MGEA5 transcripts 779:803 OGT and MGEA5 transcripts 779:803 A positive expression of OGT and MGEA5 transcripts and OGT and OGA proteins was confirmed in 75.5 and 68.9 % and in 43.7 and 59.4 % samples of SCLC, respectively. 25315705 12 3 from prognosis 1782:1790 arg1 cancer 1805:1810 laryngeal cancer 1795:1810 laryngeal cancer 1795:1810 The results suggest that increased O-GlcNAcylation may have an effect on tumor aggressiveness and prognosis in laryngeal cancer. 25315705 7 4 from levels 924:929 arg1 levels 1042:1047 total protein O-GlcNAcylation levels 1012:1047 total protein O-GlcNAcylation levels 1012:1047 Higher levels of mRNA/protein for both OGT and OGA as well as significant increases of 60 % in total protein O-GlcNAcylation levels were noted in SCLC compared with NCLM (p < 0.05). 25315705 7 5 theme O-GlcNAcylation 1026:1040 arg1 levels 1042:1047 total protein O-GlcNAcylation levels 1012:1047 total protein O-GlcNAcylation levels 1012:1047 Higher levels of mRNA/protein for both OGT and OGA as well as significant increases of 60 % in total protein O-GlcNAcylation levels were noted in SCLC compared with NCLM (p < 0.05). 25315705 6 6 theme OGT 779:781 arg1 transcripts 793:803 OGT and MGEA5 transcripts 779:803 OGT and MGEA5 transcripts 779:803 A positive expression of OGT and MGEA5 transcripts and OGT and OGA proteins was confirmed in 75.5 and 68.9 % and in 43.7 and 59.4 % samples of SCLC, respectively. 25315705 1 7 theme cancers 181:187 arg1 development 138:148 development 138:148 development 138:148 Aberrant protein O-GlcNAcylation may contribute to the development and malignant behavior of many cancers. 25315705 1 7 theme cancers 181:187 arg1 behavior 164:171 malignant behavior 154:171 malignant behavior 154:171 Aberrant protein O-GlcNAcylation may contribute to the development and malignant behavior of many cancers. 25315705 12 8 from aggressiveness 1763:1776 arg1 cancer 1805:1810 laryngeal cancer 1795:1810 laryngeal cancer 1795:1810 The results suggest that increased O-GlcNAcylation may have an effect on tumor aggressiveness and prognosis in laryngeal cancer. 25315705 4 9 theme real-time 675:683 arg1 PCR 685:687 quantitative real-time PCR 662:687 quantitative real-time PCR 662:687 The mRNA levels of OGT and MGEA5 genes were determined in 106 squamous cell laryngeal cancer (SCLC) cases and 73 non-cancerous adjacent laryngeal mucosa (NCLM) controls using quantitative real-time PCR. 25315705 7 10 theme total 1012:1016 arg1 levels 1042:1047 total protein O-GlcNAcylation levels 1012:1047 total protein O-GlcNAcylation levels 1012:1047 Higher levels of mRNA/protein for both OGT and OGA as well as significant increases of 60 % in total protein O-GlcNAcylation levels were noted in SCLC compared with NCLM (p < 0.05). 25315705 12 11 theme tumor 1757:1761 arg1 aggressiveness 1763:1776 tumor aggressiveness 1757:1776 tumor aggressiveness 1757:1776 The results suggest that increased O-GlcNAcylation may have an effect on tumor aggressiveness and prognosis in laryngeal cancer. 25315705 8 12 theme mRNA 1148:1151 arg1 level 1125:1129 an increased level 1112:1129 an increased level of OGT and MGEA5 mRNA 1112:1151 As a result, an increased level of OGT and MGEA5 mRNA was related to larger tumor size, nodal metastases, higher grade and tumor behavior according to TFG scale, as well as incidence of disease recurrence (p < 0.05). 25315705 8 12 theme mRNA 1148:1151 arg1 related 1157:1163 related 1157:1163 related 1157:1163 As a result, an increased level of OGT and MGEA5 mRNA was related to larger tumor size, nodal metastases, higher grade and tumor behavior according to TFG scale, as well as incidence of disease recurrence (p < 0.05). 25315705 7 13 theme % 1007:1007 arg1 levels 924:929 Higher levels 917:929 Higher levels of mRNA/protein for both OGT and OGA as well as significant increases of 60 % in total protein O-GlcNAcylation levels 917:1047 Higher levels of mRNA/protein for both OGT and OGA as well as significant increases of 60 % in total protein O-GlcNAcylation levels were noted in SCLC compared with NCLM (p < 0.05). 25315705 7 13 theme % 1007:1007 arg1 increases 991:999 significant increases 979:999 Higher levels of mRNA/protein for both OGT and OGA as well as significant increases of 60 % in total protein O-GlcNAcylation levels 917:1047 Higher levels of mRNA/protein for both OGT and OGA as well as significant increases of 60 % in total protein O-GlcNAcylation levels were noted in SCLC compared with NCLM (p < 0.05). 25315705 6 14 dep % 884:884 arg1 43.7 870:873 43.7 870:873 43.7 870:873 A positive expression of OGT and MGEA5 transcripts and OGT and OGA proteins was confirmed in 75.5 and 68.9 % and in 43.7 and 59.4 % samples of SCLC, respectively. 25315705 6 14 dep % 884:884 arg1 59.4 879:882 59.4 879:882 59.4 879:882 A positive expression of OGT and MGEA5 transcripts and OGT and OGA proteins was confirmed in 75.5 and 68.9 % and in 43.7 and 59.4 % samples of SCLC, respectively. 25315705 10 15 theme OGT 1450:1452 arg1 levels 1470:1475 the highest OGT and OGA protein levels 1438:1475 the highest OGT and OGA protein levels 1438:1475 In addition, the highest OGT and OGA protein levels were observed in poorly differentiated tumors (p < 0.05). 25315705 5 16 theme OGA 711:713 arg1 proteins 715:722 OGA proteins 711:722 OGA proteins 711:722 The level of OGT and OGA proteins was analyzed by Western blot. 25315705 12 17 contain have 1739:1742 arg2 effect 1747:1752 an effect 1744:1752 an effect 1744:1752 The results suggest that increased O-GlcNAcylation may have an effect on tumor aggressiveness and prognosis in laryngeal cancer. 25315705 12 17 contain have 1739:1742 arg1 O-GlcNAcylation 1719:1733 increased O-GlcNAcylation 1709:1733 increased O-GlcNAcylation 1709:1733 The results suggest that increased O-GlcNAcylation may have an effect on tumor aggressiveness and prognosis in laryngeal cancer. 25315705 8 18 theme increased 1115:1123 arg1 level 1125:1129 an increased level 1112:1129 an increased level of OGT and MGEA5 mRNA 1112:1151 As a result, an increased level of OGT and MGEA5 mRNA was related to larger tumor size, nodal metastases, higher grade and tumor behavior according to TFG scale, as well as incidence of disease recurrence (p < 0.05). 25315705 8 18 theme increased 1115:1123 arg1 related 1157:1163 related 1157:1163 related 1157:1163 As a result, an increased level of OGT and MGEA5 mRNA was related to larger tumor size, nodal metastases, higher grade and tumor behavior according to TFG scale, as well as incidence of disease recurrence (p < 0.05). 25315705 8 19 theme p 1305:1305 arg1 recurrence 1293:1302 disease recurrence 1285:1302 disease recurrence (p < 0.05) 1285:1313 As a result, an increased level of OGT and MGEA5 mRNA was related to larger tumor size, nodal metastases, higher grade and tumor behavior according to TFG scale, as well as incidence of disease recurrence (p < 0.05). 25315705 8 19 theme p 1305:1305 arg1 < 1307:1307 p < 0.05 1305:1312 p < 0.05 1305:1312 As a result, an increased level of OGT and MGEA5 mRNA was related to larger tumor size, nodal metastases, higher grade and tumor behavior according to TFG scale, as well as incidence of disease recurrence (p < 0.05). 25315705 8 20 theme larger 1168:1173 arg1 size 1181:1184 larger tumor size 1168:1184 larger tumor size 1168:1184 As a result, an increased level of OGT and MGEA5 mRNA was related to larger tumor size, nodal metastases, higher grade and tumor behavior according to TFG scale, as well as incidence of disease recurrence (p < 0.05). 25315705 7 21 theme significant 979:989 arg1 increases 991:999 significant increases 979:999 Higher levels of mRNA/protein for both OGT and OGA as well as significant increases of 60 % in total protein O-GlcNAcylation levels 917:1047 Higher levels of mRNA/protein for both OGT and OGA as well as significant increases of 60 % in total protein O-GlcNAcylation levels were noted in SCLC compared with NCLM (p < 0.05). 25315705 2 22 theme O-linked 225:232 arg1 transferase 256:266 O-linked β-N-acetylglucosamine transferase 225:266 O-linked β-N-acetylglucosamine transferase (OGT) 225:272 This modification is controlled by O-linked β-N-acetylglucosamine transferase (OGT) and O-GlcNAcase (OGA). 25315705 2 22 theme O-linked 225:232 arg1 OGT 269:271 OGT 269:271 OGT 269:271 This modification is controlled by O-linked β-N-acetylglucosamine transferase (OGT) and O-GlcNAcase (OGA). 25315705 7 23 theme mRNA/protein 934:945 arg1 levels 924:929 Higher levels 917:929 Higher levels of mRNA/protein for both OGT and OGA as well as significant increases of 60 % in total protein O-GlcNAcylation levels 917:1047 Higher levels of mRNA/protein for both OGT and OGA as well as significant increases of 60 % in total protein O-GlcNAcylation levels were noted in SCLC compared with NCLM (p < 0.05). 25315705 7 23 theme mRNA/protein 934:945 arg1 increases 991:999 significant increases 979:999 Higher levels of mRNA/protein for both OGT and OGA as well as significant increases of 60 % in total protein O-GlcNAcylation levels 917:1047 Higher levels of mRNA/protein for both OGT and OGA as well as significant increases of 60 % in total protein O-GlcNAcylation levels were noted in SCLC compared with NCLM (p < 0.05). 25315705 8 24 theme nodal 1187:1191 arg1 metastases 1193:1202 nodal metastases 1187:1202 nodal metastases 1187:1202 As a result, an increased level of OGT and MGEA5 mRNA was related to larger tumor size, nodal metastases, higher grade and tumor behavior according to TFG scale, as well as incidence of disease recurrence (p < 0.05). 25315705 0 25 theme human 59:63 arg1 cancer 75:80 human laryngeal cancer 59:80 human laryngeal cancer 59:80 Gene and protein expression of O-GlcNAc-cycling enzymes in human laryngeal cancer. 25315705 0 26 theme protein 9:15 arg1 expression 17:26 Gene and protein expression 0:26 Gene and protein expression of O-GlcNAc-cycling enzymes in human laryngeal cancer. 0:81 Gene and protein expression of O-GlcNAc-cycling enzymes in human laryngeal cancer. 25315705 11 27 with correlations 1538:1549 arg1 parameters 1562:1571 other parameters 1556:1571 other parameters 1556:1571 No correlations with other parameters were noted, but the results showed a trend of more advanced tumors to be more frequently OGT and OGA positive. 25315705 1 28 theme malignant 154:162 arg1 behavior 164:171 malignant behavior 154:171 malignant behavior 154:171 Aberrant protein O-GlcNAcylation may contribute to the development and malignant behavior of many cancers. 25315705 3 29 theme study 313:317 arg1 aim 301:303 The aim 297:303 The aim of this study 297:317 The aim of this study was to determine the expression of O-GlcNAc cycling enzymes mRNA/protein and to investigate their relationship with clinicopathological parameters in laryngeal cancer. 25315705 4 30 theme genes 520:524 arg1 levels 496:501 The mRNA levels 487:501 The mRNA levels of OGT and MGEA5 genes 487:524 The mRNA levels of OGT and MGEA5 genes were determined in 106 squamous cell laryngeal cancer (SCLC) cases and 73 non-cancerous adjacent laryngeal mucosa (NCLM) controls using quantitative real-time PCR. 25315705 11 31 theme other 1556:1560 arg1 parameters 1562:1571 other parameters 1556:1571 other parameters 1556:1571 No correlations with other parameters were noted, but the results showed a trend of more advanced tumors to be more frequently OGT and OGA positive. 25315705 4 32 theme mRNA 491:494 arg1 levels 496:501 The mRNA levels 487:501 The mRNA levels of OGT and MGEA5 genes 487:524 The mRNA levels of OGT and MGEA5 genes were determined in 106 squamous cell laryngeal cancer (SCLC) cases and 73 non-cancerous adjacent laryngeal mucosa (NCLM) controls using quantitative real-time PCR. 25315705 8 33 theme tumor 1222:1226 arg1 behavior 1228:1235 tumor behavior 1222:1235 tumor behavior 1222:1235 As a result, an increased level of OGT and MGEA5 mRNA was related to larger tumor size, nodal metastases, higher grade and tumor behavior according to TFG scale, as well as incidence of disease recurrence (p < 0.05). 25315705 10 34 theme protein 1462:1468 arg1 levels 1470:1475 the highest OGT and OGA protein levels 1438:1475 the highest OGT and OGA protein levels 1438:1475 In addition, the highest OGT and OGA protein levels were observed in poorly differentiated tumors (p < 0.05). 25315705 3 35 theme mRNA/protein 379:390 arg1 expression 340:349 the expression 336:349 the expression of O-GlcNAc cycling enzymes mRNA/protein 336:390 The aim of this study was to determine the expression of O-GlcNAc cycling enzymes mRNA/protein and to investigate their relationship with clinicopathological parameters in laryngeal cancer. 25315705 0 36 theme laryngeal 65:73 arg1 cancer 75:80 human laryngeal cancer 59:80 human laryngeal cancer 59:80 Gene and protein expression of O-GlcNAc-cycling enzymes in human laryngeal cancer. 25315705 0 37 theme Gene 0:3 arg1 expression 17:26 Gene and protein expression 0:26 Gene and protein expression of O-GlcNAc-cycling enzymes in human laryngeal cancer. 0:81 Gene and protein expression of O-GlcNAc-cycling enzymes in human laryngeal cancer. 25315705 1 38 theme protein 92:98 arg1 O-GlcNAcylation 100:114 Aberrant protein O-GlcNAcylation 83:114 Aberrant protein O-GlcNAcylation 83:114 Aberrant protein O-GlcNAcylation may contribute to the development and malignant behavior of many cancers. 25315705 3 39 theme cycling 363:369 arg1 mRNA/protein 379:390 O-GlcNAc cycling enzymes mRNA/protein 354:390 O-GlcNAc cycling enzymes mRNA/protein 354:390 The aim of this study was to determine the expression of O-GlcNAc cycling enzymes mRNA/protein and to investigate their relationship with clinicopathological parameters in laryngeal cancer. 25315705 4 40 theme cell 558:561 arg1 SCLC 581:584 SCLC 581:584 SCLC 581:584 The mRNA levels of OGT and MGEA5 genes were determined in 106 squamous cell laryngeal cancer (SCLC) cases and 73 non-cancerous adjacent laryngeal mucosa (NCLM) controls using quantitative real-time PCR. 25315705 4 40 theme cell 558:561 arg1 cancer 573:578 squamous cell laryngeal cancer 549:578 106 squamous cell laryngeal cancer (SCLC) cases 545:591 The mRNA levels of OGT and MGEA5 genes were determined in 106 squamous cell laryngeal cancer (SCLC) cases and 73 non-cancerous adjacent laryngeal mucosa (NCLM) controls using quantitative real-time PCR. 25315705 8 41 theme TFG 1250:1252 arg1 scale 1254:1258 TFG scale 1250:1258 TFG scale 1250:1258 As a result, an increased level of OGT and MGEA5 mRNA was related to larger tumor size, nodal metastases, higher grade and tumor behavior according to TFG scale, as well as incidence of disease recurrence (p < 0.05). 25315705 7 42 theme p 1088:1088 arg1 NCLM 1082:1085 NCLM 1082:1085 NCLM (p < 0.05) 1082:1096 Higher levels of mRNA/protein for both OGT and OGA as well as significant increases of 60 % in total protein O-GlcNAcylation levels were noted in SCLC compared with NCLM (p < 0.05). 25315705 7 42 theme p 1088:1088 arg1 < 1090:1090 p < 0.05 1088:1095 p < 0.05 1088:1095 Higher levels of mRNA/protein for both OGT and OGA as well as significant increases of 60 % in total protein O-GlcNAcylation levels were noted in SCLC compared with NCLM (p < 0.05). 25315705 6 43 theme 75.5 847:850 arg1 % 861:861 75.5 and 68.9 % 847:861 % 861:861 A positive expression of OGT and MGEA5 transcripts and OGT and OGA proteins was confirmed in 75.5 and 68.9 % and in 43.7 and 59.4 % samples of SCLC, respectively. 25315705 4 44 theme cancer 573:578 arg1 cases 587:591 106 squamous cell laryngeal cancer (SCLC) cases 545:591 106 squamous cell laryngeal cancer (SCLC) cases 545:591 The mRNA levels of OGT and MGEA5 genes were determined in 106 squamous cell laryngeal cancer (SCLC) cases and 73 non-cancerous adjacent laryngeal mucosa (NCLM) controls using quantitative real-time PCR. 25315705 3 45 theme laryngeal 469:477 arg1 cancer 479:484 laryngeal cancer 469:484 laryngeal cancer 469:484 The aim of this study was to determine the expression of O-GlcNAc cycling enzymes mRNA/protein and to investigate their relationship with clinicopathological parameters in laryngeal cancer. 25315705 11 46 theme tumors 1633:1638 arg1 trend 1610:1614 a trend 1608:1614 a trend of more advanced tumors 1608:1638 No correlations with other parameters were noted, but the results showed a trend of more advanced tumors to be more frequently OGT and OGA positive. 25315705 0 47 theme enzymes 48:54 arg1 expression 17:26 Gene and protein expression 0:26 Gene and protein expression of O-GlcNAc-cycling enzymes in human laryngeal cancer. 0:81 Gene and protein expression of O-GlcNAc-cycling enzymes in human laryngeal cancer. 25315705 0 48 from expression 17:26 arg1 cancer 75:80 human laryngeal cancer 59:80 human laryngeal cancer 59:80 Gene and protein expression of O-GlcNAc-cycling enzymes in human laryngeal cancer. 25315705 6 49 theme proteins 821:828 arg1 expression 765:774 A positive expression 754:774 A positive expression of OGT and MGEA5 transcripts and OGT and OGA proteins 754:828 A positive expression of OGT and MGEA5 transcripts and OGT and OGA proteins was confirmed in 75.5 and 68.9 % and in 43.7 and 59.4 % samples of SCLC, respectively. 25315705 9 50 dep OGT 1347:1349 arg1 transcripts 1361:1371 transcripts 1361:1371 transcripts 1361:1371 An inverse association between OGT and MGEA5 transcripts was determined with regard to prognosis (p < 0.05). 25315705 10 51 theme differentiated 1501:1514 arg1 tumors 1516:1521 poorly differentiated tumors 1494:1521 poorly differentiated tumors (p < 0.05) 1494:1532 In addition, the highest OGT and OGA protein levels were observed in poorly differentiated tumors (p < 0.05). 25315705 10 51 theme differentiated 1501:1514 arg1 < 1526:1526 p < 0.05 1524:1531 p < 0.05 1524:1531 In addition, the highest OGT and OGA protein levels were observed in poorly differentiated tumors (p < 0.05). 25315705 8 52 theme disease 1285:1291 arg1 recurrence 1293:1302 disease recurrence 1285:1302 disease recurrence (p < 0.05) 1285:1313 As a result, an increased level of OGT and MGEA5 mRNA was related to larger tumor size, nodal metastases, higher grade and tumor behavior according to TFG scale, as well as incidence of disease recurrence (p < 0.05). 25315705 8 52 theme disease 1285:1291 arg1 < 1307:1307 p < 0.05 1305:1312 p < 0.05 1305:1312 As a result, an increased level of OGT and MGEA5 mRNA was related to larger tumor size, nodal metastases, higher grade and tumor behavior according to TFG scale, as well as incidence of disease recurrence (p < 0.05). 25315705 12 53 theme laryngeal 1795:1803 arg1 cancer 1805:1810 laryngeal cancer 1795:1810 laryngeal cancer 1795:1810 The results suggest that increased O-GlcNAcylation may have an effect on tumor aggressiveness and prognosis in laryngeal cancer. 25315705 4 54 theme adjacent 614:621 arg1 controls 647:654 73 non-cancerous adjacent laryngeal mucosa (NCLM) controls 597:654 73 non-cancerous adjacent laryngeal mucosa (NCLM) controls 597:654 The mRNA levels of OGT and MGEA5 genes were determined in 106 squamous cell laryngeal cancer (SCLC) cases and 73 non-cancerous adjacent laryngeal mucosa (NCLM) controls using quantitative real-time PCR. 25315705 10 55 located observed 1482:1489 arg1 tumors 1516:1521 poorly differentiated tumors 1494:1521 poorly differentiated tumors (p < 0.05) 1494:1532 In addition, the highest OGT and OGA protein levels were observed in poorly differentiated tumors (p < 0.05). 25315705 10 55 located observed 1482:1489 arg1 < 1526:1526 p < 0.05 1524:1531 p < 0.05 1524:1531 In addition, the highest OGT and OGA protein levels were observed in poorly differentiated tumors (p < 0.05). 25315705 10 55 located observed 1482:1489 arg2 levels 1470:1475 the highest OGT and OGA protein levels 1438:1475 the highest OGT and OGA protein levels 1438:1475 In addition, the highest OGT and OGA protein levels were observed in poorly differentiated tumors (p < 0.05). 25315705 10 55 located observed 1482:1489 arg1 addition 1428:1435 addition 1428:1435 addition 1428:1435 In addition, the highest OGT and OGA protein levels were observed in poorly differentiated tumors (p < 0.05). 25315705 8 56 theme recurrence 1293:1302 arg1 incidence 1272:1280 incidence 1272:1280 incidence of disease recurrence (p < 0.05) 1272:1313 As a result, an increased level of OGT and MGEA5 mRNA was related to larger tumor size, nodal metastases, higher grade and tumor behavior according to TFG scale, as well as incidence of disease recurrence (p < 0.05). 25315705 6 57 theme transcripts 793:803 arg1 expression 765:774 A positive expression 754:774 A positive expression of OGT and MGEA5 transcripts and OGT and OGA proteins 754:828 A positive expression of OGT and MGEA5 transcripts and OGT and OGA proteins was confirmed in 75.5 and 68.9 % and in 43.7 and 59.4 % samples of SCLC, respectively. 25315705 7 58 theme protein 1018:1024 arg1 levels 1042:1047 total protein O-GlcNAcylation levels 1012:1047 total protein O-GlcNAcylation levels 1012:1047 Higher levels of mRNA/protein for both OGT and OGA as well as significant increases of 60 % in total protein O-GlcNAcylation levels were noted in SCLC compared with NCLM (p < 0.05). 25315705 1 59 theme many 176:179 arg1 cancers 181:187 many cancers 176:187 many cancers 176:187 Aberrant protein O-GlcNAcylation may contribute to the development and malignant behavior of many cancers. 25315705 6 60 theme 68.9 856:859 arg1 % 861:861 75.5 and 68.9 % 847:861 % 861:861 A positive expression of OGT and MGEA5 transcripts and OGT and OGA proteins was confirmed in 75.5 and 68.9 % and in 43.7 and 59.4 % samples of SCLC, respectively. 25315705 3 61 with relationship 417:428 arg1 parameters 455:464 clinicopathological parameters 435:464 clinicopathological parameters in laryngeal cancer 435:484 The aim of this study was to determine the expression of O-GlcNAc cycling enzymes mRNA/protein and to investigate their relationship with clinicopathological parameters in laryngeal cancer. 25315705 8 62 theme OGT 1134:1136 arg1 level 1125:1129 an increased level 1112:1129 an increased level of OGT and MGEA5 mRNA 1112:1151 As a result, an increased level of OGT and MGEA5 mRNA was related to larger tumor size, nodal metastases, higher grade and tumor behavior according to TFG scale, as well as incidence of disease recurrence (p < 0.05). 25315705 8 62 theme OGT 1134:1136 arg1 related 1157:1163 related 1157:1163 related 1157:1163 As a result, an increased level of OGT and MGEA5 mRNA was related to larger tumor size, nodal metastases, higher grade and tumor behavior according to TFG scale, as well as incidence of disease recurrence (p < 0.05). 25315705 6 63 theme positive 756:763 arg1 expression 765:774 A positive expression 754:774 A positive expression of OGT and MGEA5 transcripts and OGT and OGA proteins 754:828 A positive expression of OGT and MGEA5 transcripts and OGT and OGA proteins was confirmed in 75.5 and 68.9 % and in 43.7 and 59.4 % samples of SCLC, respectively. 25315705 6 64 dep samples 886:892 arg1 % 884:884 % 884:884 % 884:884 A positive expression of OGT and MGEA5 transcripts and OGT and OGA proteins was confirmed in 75.5 and 68.9 % and in 43.7 and 59.4 % samples of SCLC, respectively. 25315705 8 65 theme MGEA5 1142:1146 arg1 mRNA 1148:1151 MGEA5 mRNA 1142:1151 MGEA5 mRNA 1142:1151 As a result, an increased level of OGT and MGEA5 mRNA was related to larger tumor size, nodal metastases, higher grade and tumor behavior according to TFG scale, as well as incidence of disease recurrence (p < 0.05). 25315705 10 66 theme highest 1442:1448 arg1 levels 1470:1475 the highest OGT and OGA protein levels 1438:1475 the highest OGT and OGA protein levels 1438:1475 In addition, the highest OGT and OGA protein levels were observed in poorly differentiated tumors (p < 0.05). 25315705 4 67 theme quantitative 662:673 arg1 PCR 685:687 quantitative real-time PCR 662:687 quantitative real-time PCR 662:687 The mRNA levels of OGT and MGEA5 genes were determined in 106 squamous cell laryngeal cancer (SCLC) cases and 73 non-cancerous adjacent laryngeal mucosa (NCLM) controls using quantitative real-time PCR. 25315705 12 68 theme increased 1709:1717 arg1 O-GlcNAcylation 1719:1733 increased O-GlcNAcylation 1709:1733 increased O-GlcNAcylation 1709:1733 The results suggest that increased O-GlcNAcylation may have an effect on tumor aggressiveness and prognosis in laryngeal cancer. 25315705 6 69 theme SCLC 897:900 arg1 samples 886:892 43.7 and 59.4 % samples 870:892 43.7 and 59.4 % samples 870:892 A positive expression of OGT and MGEA5 transcripts and OGT and OGA proteins was confirmed in 75.5 and 68.9 % and in 43.7 and 59.4 % samples of SCLC, respectively. 25315705 4 70 theme NCLM 641:644 arg1 controls 647:654 73 non-cancerous adjacent laryngeal mucosa (NCLM) controls 597:654 73 non-cancerous adjacent laryngeal mucosa (NCLM) controls 597:654 The mRNA levels of OGT and MGEA5 genes were determined in 106 squamous cell laryngeal cancer (SCLC) cases and 73 non-cancerous adjacent laryngeal mucosa (NCLM) controls using quantitative real-time PCR. 25315705 2 71 theme β-N-acetylglucosamine 234:254 arg1 transferase 256:266 O-linked β-N-acetylglucosamine transferase 225:266 O-linked β-N-acetylglucosamine transferase (OGT) 225:272 This modification is controlled by O-linked β-N-acetylglucosamine transferase (OGT) and O-GlcNAcase (OGA). 25315705 2 71 theme β-N-acetylglucosamine 234:254 arg1 OGT 269:271 OGT 269:271 OGT 269:271 This modification is controlled by O-linked β-N-acetylglucosamine transferase (OGT) and O-GlcNAcase (OGA). 25315705 9 72 theme inverse 1319:1325 arg1 association 1327:1337 An inverse association 1316:1337 An inverse association between OGT and MGEA5 transcripts 1316:1371 An inverse association between OGT and MGEA5 transcripts was determined with regard to prognosis (p < 0.05). 25315705 8 73 theme tumor 1175:1179 arg1 size 1181:1184 larger tumor size 1168:1184 larger tumor size 1168:1184 As a result, an increased level of OGT and MGEA5 mRNA was related to larger tumor size, nodal metastases, higher grade and tumor behavior according to TFG scale, as well as incidence of disease recurrence (p < 0.05). 25315705 2 74 link O-linked 225:232 arg1 transferase 256:266 O-linked β-N-acetylglucosamine transferase 225:266 O-linked β-N-acetylglucosamine transferase (OGT) 225:272 This modification is controlled by O-linked β-N-acetylglucosamine transferase (OGT) and O-GlcNAcase (OGA). 25315705 2 74 link O-linked 225:232 arg1 OGT 269:271 OGT 269:271 OGT 269:271 This modification is controlled by O-linked β-N-acetylglucosamine transferase (OGT) and O-GlcNAcase (OGA). 25315705 5 75 theme Western 740:746 arg1 blot 748:751 Western blot 740:751 Western blot 740:751 The level of OGT and OGA proteins was analyzed by Western blot. 25315705 4 76 theme MGEA5 514:518 arg1 genes 520:524 MGEA5 genes 514:524 MGEA5 genes 514:524 The mRNA levels of OGT and MGEA5 genes were determined in 106 squamous cell laryngeal cancer (SCLC) cases and 73 non-cancerous adjacent laryngeal mucosa (NCLM) controls using quantitative real-time PCR. 25315705 5 77 theme OGT 703:705 arg1 level 694:698 The level 690:698 The level of OGT and OGA proteins 690:722 The level of OGT and OGA proteins was analyzed by Western blot. 25315705 5 78 theme proteins 715:722 arg1 level 694:698 The level 690:698 The level of OGT and OGA proteins 690:722 The level of OGT and OGA proteins was analyzed by Western blot. 25315705 7 79 theme Higher 917:922 arg1 levels 924:929 Higher levels 917:929 Higher levels of mRNA/protein for both OGT and OGA as well as significant increases of 60 % in total protein O-GlcNAcylation levels 917:1047 Higher levels of mRNA/protein for both OGT and OGA as well as significant increases of 60 % in total protein O-GlcNAcylation levels were noted in SCLC compared with NCLM (p < 0.05). 25315705 3 80 theme O-GlcNAc 354:361 arg1 mRNA/protein 379:390 O-GlcNAc cycling enzymes mRNA/protein 354:390 O-GlcNAc cycling enzymes mRNA/protein 354:390 The aim of this study was to determine the expression of O-GlcNAc cycling enzymes mRNA/protein and to investigate their relationship with clinicopathological parameters in laryngeal cancer. 25315705 1 81 dep development 138:148 arg1 the 134:136 the 134:136 the 134:136 Aberrant protein O-GlcNAcylation may contribute to the development and malignant behavior of many cancers. 25315705 8 82 theme higher 1205:1210 arg1 grade 1212:1216 higher grade 1205:1216 higher grade 1205:1216 As a result, an increased level of OGT and MGEA5 mRNA was related to larger tumor size, nodal metastases, higher grade and tumor behavior according to TFG scale, as well as incidence of disease recurrence (p < 0.05). 25315705 4 83 theme mucosa 633:638 arg1 controls 647:654 73 non-cancerous adjacent laryngeal mucosa (NCLM) controls 597:654 73 non-cancerous adjacent laryngeal mucosa (NCLM) controls 597:654 The mRNA levels of OGT and MGEA5 genes were determined in 106 squamous cell laryngeal cancer (SCLC) cases and 73 non-cancerous adjacent laryngeal mucosa (NCLM) controls using quantitative real-time PCR. 25315705 4 84 theme OGT 506:508 arg1 levels 496:501 The mRNA levels 487:501 The mRNA levels of OGT and MGEA5 genes 487:524 The mRNA levels of OGT and MGEA5 genes were determined in 106 squamous cell laryngeal cancer (SCLC) cases and 73 non-cancerous adjacent laryngeal mucosa (NCLM) controls using quantitative real-time PCR. 25315705 10 85 theme OGA 1458:1460 arg1 levels 1470:1475 the highest OGT and OGA protein levels 1438:1475 the highest OGT and OGA protein levels 1438:1475 In addition, the highest OGT and OGA protein levels were observed in poorly differentiated tumors (p < 0.05). 25315705 1 86 theme Aberrant 83:90 arg1 O-GlcNAcylation 100:114 Aberrant protein O-GlcNAcylation 83:114 Aberrant protein O-GlcNAcylation 83:114 Aberrant protein O-GlcNAcylation may contribute to the development and malignant behavior of many cancers. 25315705 4 87 theme laryngeal 563:571 arg1 SCLC 581:584 SCLC 581:584 SCLC 581:584 The mRNA levels of OGT and MGEA5 genes were determined in 106 squamous cell laryngeal cancer (SCLC) cases and 73 non-cancerous adjacent laryngeal mucosa (NCLM) controls using quantitative real-time PCR. 25315705 4 87 theme laryngeal 563:571 arg1 cancer 573:578 squamous cell laryngeal cancer 549:578 106 squamous cell laryngeal cancer (SCLC) cases 545:591 The mRNA levels of OGT and MGEA5 genes were determined in 106 squamous cell laryngeal cancer (SCLC) cases and 73 non-cancerous adjacent laryngeal mucosa (NCLM) controls using quantitative real-time PCR. 25315705 3 88 theme clinicopathological 435:453 arg1 parameters 455:464 clinicopathological parameters 435:464 clinicopathological parameters in laryngeal cancer 435:484 The aim of this study was to determine the expression of O-GlcNAc cycling enzymes mRNA/protein and to investigate their relationship with clinicopathological parameters in laryngeal cancer. 25315705 9 89 theme p 1414:1414 arg1 prognosis 1403:1411 prognosis 1403:1411 prognosis (p < 0.05) 1403:1422 An inverse association between OGT and MGEA5 transcripts was determined with regard to prognosis (p < 0.05). 25315705 9 89 theme p 1414:1414 arg1 < 1416:1416 p < 0.05 1414:1421 p < 0.05 1414:1421 An inverse association between OGT and MGEA5 transcripts was determined with regard to prognosis (p < 0.05). 25315705 3 90 theme enzymes 371:377 arg1 mRNA/protein 379:390 O-GlcNAc cycling enzymes mRNA/protein 354:390 O-GlcNAc cycling enzymes mRNA/protein 354:390 The aim of this study was to determine the expression of O-GlcNAc cycling enzymes mRNA/protein and to investigate their relationship with clinicopathological parameters in laryngeal cancer. 25315705 0 91 theme O-GlcNAc-cycling 31:46 arg1 enzymes 48:54 O-GlcNAc-cycling enzymes 31:54 O-GlcNAc-cycling enzymes 31:54 Gene and protein expression of O-GlcNAc-cycling enzymes in human laryngeal cancer. 25315705 4 92 theme squamous 549:556 arg1 SCLC 581:584 SCLC 581:584 SCLC 581:584 The mRNA levels of OGT and MGEA5 genes were determined in 106 squamous cell laryngeal cancer (SCLC) cases and 73 non-cancerous adjacent laryngeal mucosa (NCLM) controls using quantitative real-time PCR. 25315705 4 92 theme squamous 549:556 arg1 cancer 573:578 squamous cell laryngeal cancer 549:578 106 squamous cell laryngeal cancer (SCLC) cases 545:591 The mRNA levels of OGT and MGEA5 genes were determined in 106 squamous cell laryngeal cancer (SCLC) cases and 73 non-cancerous adjacent laryngeal mucosa (NCLM) controls using quantitative real-time PCR. 25315705 6 93 theme OGA 817:819 arg1 proteins 821:828 OGT and OGA proteins 809:828 OGT and OGA proteins 809:828 A positive expression of OGT and MGEA5 transcripts and OGT and OGA proteins was confirmed in 75.5 and 68.9 % and in 43.7 and 59.4 % samples of SCLC, respectively. 25315705 4 94 theme non-cancerous 600:612 arg1 controls 647:654 73 non-cancerous adjacent laryngeal mucosa (NCLM) controls 597:654 73 non-cancerous adjacent laryngeal mucosa (NCLM) controls 597:654 The mRNA levels of OGT and MGEA5 genes were determined in 106 squamous cell laryngeal cancer (SCLC) cases and 73 non-cancerous adjacent laryngeal mucosa (NCLM) controls using quantitative real-time PCR. 25315705 11 95 theme advanced 1624:1631 arg1 tumors 1633:1638 more advanced tumors 1619:1638 more advanced tumors 1619:1638 No correlations with other parameters were noted, but the results showed a trend of more advanced tumors to be more frequently OGT and OGA positive. 25315705 6 96 theme OGT 809:811 arg1 proteins 821:828 OGT and OGA proteins 809:828 OGT and OGA proteins 809:828 A positive expression of OGT and MGEA5 transcripts and OGT and OGA proteins was confirmed in 75.5 and 68.9 % and in 43.7 and 59.4 % samples of SCLC, respectively. 25315705 4 97 theme laryngeal 623:631 arg1 controls 647:654 73 non-cancerous adjacent laryngeal mucosa (NCLM) controls 597:654 73 non-cancerous adjacent laryngeal mucosa (NCLM) controls 597:654 The mRNA levels of OGT and MGEA5 genes were determined in 106 squamous cell laryngeal cancer (SCLC) cases and 73 non-cancerous adjacent laryngeal mucosa (NCLM) controls using quantitative real-time PCR. 25315705 3 98 from parameters 455:464 arg1 cancer 479:484 laryngeal cancer 469:484 laryngeal cancer 469:484 The aim of this study was to determine the expression of O-GlcNAc cycling enzymes mRNA/protein and to investigate their relationship with clinicopathological parameters in laryngeal cancer. 24968300 5 0 dep N-acetylglucosamine 851:869 arg1 modification 871:882 modification 871:882 the O-linked N-acetylglucosamine modification (O-GlcNAcylation) of RNAPII 838:910 LPS reduced the O-linked N-acetylglucosamine modification (O-GlcNAcylation) of RNAPII, but enhanced the binding of this enzyme to the iNOS promoter. 24968300 3 1 theme FINDINGS 509:516 arg1 activities 540:549 KEY FINDINGS Basal transcriptional activities 505:549 KEY FINDINGS Basal transcriptional activities of nuclear factor-κB (NF-κB) and nitric oxide synthase (iNOS) reporter plasmids 505:629 KEY FINDINGS Basal transcriptional activities of nuclear factor-κB (NF-κB) and nitric oxide synthase (iNOS) reporter plasmids are inhibited by GlcN in RAW264.7 cells. 24968300 7 2 theme plasmids 1109:1116 arg1 activities 1086:1095 the basal activities 1076:1095 the basal activities of reporter plasmids containing activator protein 1 (AP1), E2F, or cyclic AMP response element (CRE) binding sites 1076:1210 Furthermore, the basal activities of reporter plasmids containing activator protein 1 (AP1), E2F, or cyclic AMP response element (CRE) binding sites were consistently inhibited by GlcN in a dose-dependent manner. 24968300 3 3 theme Basal 518:522 arg1 activities 540:549 KEY FINDINGS Basal transcriptional activities 505:549 KEY FINDINGS Basal transcriptional activities of nuclear factor-κB (NF-κB) and nitric oxide synthase (iNOS) reporter plasmids 505:629 KEY FINDINGS Basal transcriptional activities of nuclear factor-κB (NF-κB) and nitric oxide synthase (iNOS) reporter plasmids are inhibited by GlcN in RAW264.7 cells. 24968300 1 4 theme transcriptional 220:234 arg1 regulator 236:244 a transcriptional regulator 218:244 a transcriptional regulator of iNOS 218:252 AIMS The objective of this study is to investigate glucosamine (GlcN) as a transcriptional regulator of iNOS and other genes in association with the dynamic O-GlcNAcylation of RNA polymerase II (RNAPII). 24968300 1 4 theme transcriptional 220:234 arg1 glucosamine 196:206 glucosamine 196:206 glucosamine (GlcN) 196:213 AIMS The objective of this study is to investigate glucosamine (GlcN) as a transcriptional regulator of iNOS and other genes in association with the dynamic O-GlcNAcylation of RNA polymerase II (RNAPII). 24968300 0 5 theme binding 97:103 arg1 regulation 79:88 the regulation 75:88 the regulation of DNA binding of RNA polymerase II in RAW264.7 cells 75:142 Basal transcription is regulated by lipopolysaccharide and glucosamine via the regulation of DNA binding of RNA polymerase II in RAW264.7 cells. 24968300 1 6 theme RNA 321:323 arg1 polymerase 325:334 RNA polymerase II 321:337 RNA polymerase II (RNAPII) 321:346 AIMS The objective of this study is to investigate glucosamine (GlcN) as a transcriptional regulator of iNOS and other genes in association with the dynamic O-GlcNAcylation of RNA polymerase II (RNAPII). 24968300 1 6 theme RNA 321:323 arg1 RNAPII 340:345 RNAPII 340:345 RNAPII 340:345 AIMS The objective of this study is to investigate glucosamine (GlcN) as a transcriptional regulator of iNOS and other genes in association with the dynamic O-GlcNAcylation of RNA polymerase II (RNAPII). 24968300 3 7 theme factor-κB 562:570 arg1 plasmids 622:629 nuclear factor-κB (NF-κB) and nitric oxide synthase (iNOS) reporter plasmids 554:629 nuclear factor-κB (NF-κB) and nitric oxide synthase (iNOS) reporter plasmids 554:629 KEY FINDINGS Basal transcriptional activities of nuclear factor-κB (NF-κB) and nitric oxide synthase (iNOS) reporter plasmids are inhibited by GlcN in RAW264.7 cells. 24968300 0 8 theme DNA 93:95 arg1 binding 97:103 DNA binding 93:103 DNA binding of RNA polymerase II 93:124 Basal transcription is regulated by lipopolysaccharide and glucosamine via the regulation of DNA binding of RNA polymerase II in RAW264.7 cells. 24968300 1 9 theme polymerase 325:334 arg1 O-GlcNAcylation 302:316 the dynamic O-GlcNAcylation 290:316 the dynamic O-GlcNAcylation of RNA polymerase II (RNAPII) 290:346 AIMS The objective of this study is to investigate glucosamine (GlcN) as a transcriptional regulator of iNOS and other genes in association with the dynamic O-GlcNAcylation of RNA polymerase II (RNAPII). 24968300 10 10 theme O-GlcNAcylation 1693:1707 arg1 regulation 1672:1681 the regulation 1668:1681 the regulation of RNAPII O-GlcNAcylation and DNA binding 1668:1723 SIGNIFICANCE In conclusion, our data demonstrate that LPS activates, whereas GlcN suppresses, basal activities of transcription through the regulation of RNAPII O-GlcNAcylation and DNA binding. 24968300 0 11 theme RNA 108:110 arg1 polymerase 112:121 RNA polymerase II 108:124 RNA polymerase II 108:124 Basal transcription is regulated by lipopolysaccharide and glucosamine via the regulation of DNA binding of RNA polymerase II in RAW264.7 cells. 24968300 10 12 theme binding 1717:1723 arg1 regulation 1672:1681 the regulation 1668:1681 the regulation of RNAPII O-GlcNAcylation and DNA binding 1668:1723 SIGNIFICANCE In conclusion, our data demonstrate that LPS activates, whereas GlcN suppresses, basal activities of transcription through the regulation of RNAPII O-GlcNAcylation and DNA binding. 24968300 7 13 theme response 1175:1182 arg1 CRE 1193:1195 CRE 1193:1195 CRE 1193:1195 Furthermore, the basal activities of reporter plasmids containing activator protein 1 (AP1), E2F, or cyclic AMP response element (CRE) binding sites were consistently inhibited by GlcN in a dose-dependent manner. 24968300 7 13 theme response 1175:1182 arg1 element 1184:1190 cyclic AMP response element 1164:1190 cyclic AMP response element (CRE) binding sites 1164:1210 Furthermore, the basal activities of reporter plasmids containing activator protein 1 (AP1), E2F, or cyclic AMP response element (CRE) binding sites were consistently inhibited by GlcN in a dose-dependent manner. 24968300 1 14 with association 273:283 arg1 O-GlcNAcylation 302:316 the dynamic O-GlcNAcylation 290:316 the dynamic O-GlcNAcylation of RNA polymerase II (RNAPII) 290:346 AIMS The objective of this study is to investigate glucosamine (GlcN) as a transcriptional regulator of iNOS and other genes in association with the dynamic O-GlcNAcylation of RNA polymerase II (RNAPII). 24968300 4 15 theme reporter 805:812 arg1 constructs 814:823 Gal4-binding site/TATA-box-containing reporter constructs 767:823 Gal4-binding site/TATA-box-containing reporter constructs 767:823 Furthermore, GlcN suppressed whereas lipopolysaccharide (LPS) stimulated the basal activity of Gal4-binding site/TATA-box-containing reporter constructs. 24968300 10 16 theme transcription 1646:1658 arg1 activities 1632:1641 basal activities 1626:1641 basal activities of transcription 1626:1658 SIGNIFICANCE In conclusion, our data demonstrate that LPS activates, whereas GlcN suppresses, basal activities of transcription through the regulation of RNAPII O-GlcNAcylation and DNA binding. 24968300 5 17 theme RNAPII 905:910 arg1 N-acetylglucosamine 851:869 the O-linked N-acetylglucosamine 838:869 the O-linked N-acetylglucosamine modification (O-GlcNAcylation) of RNAPII 838:910 LPS reduced the O-linked N-acetylglucosamine modification (O-GlcNAcylation) of RNAPII, but enhanced the binding of this enzyme to the iNOS promoter. 24968300 5 17 theme RNAPII 905:910 arg1 O-GlcNAcylation 885:899 O-GlcNAcylation 885:899 O-GlcNAcylation 885:899 LPS reduced the O-linked N-acetylglucosamine modification (O-GlcNAcylation) of RNAPII, but enhanced the binding of this enzyme to the iNOS promoter. 24968300 9 18 theme transcriptional 1418:1432 arg1 activity 1434:1441 The transcriptional activity 1414:1441 The transcriptional activity of transforming growth factor alpha (TGF-α) 1414:1485 The transcriptional activity of transforming growth factor alpha (TGF-α) was slightly increased by both LPS and GlcN. 24968300 1 19 from genes 264:268 arg1 association 273:283 association 273:283 association with the dynamic O-GlcNAcylation of RNA polymerase II (RNAPII) 273:346 AIMS The objective of this study is to investigate glucosamine (GlcN) as a transcriptional regulator of iNOS and other genes in association with the dynamic O-GlcNAcylation of RNA polymerase II (RNAPII). 24968300 3 20 theme nuclear 554:560 arg1 factor-κB 562:570 nuclear factor-κB 554:570 nuclear factor-κB (NF-κB) 554:578 KEY FINDINGS Basal transcriptional activities of nuclear factor-κB (NF-κB) and nitric oxide synthase (iNOS) reporter plasmids are inhibited by GlcN in RAW264.7 cells. 24968300 3 20 theme nuclear 554:560 arg1 NF-κB 573:577 NF-κB 573:577 NF-κB 573:577 KEY FINDINGS Basal transcriptional activities of nuclear factor-κB (NF-κB) and nitric oxide synthase (iNOS) reporter plasmids are inhibited by GlcN in RAW264.7 cells. 24968300 2 21 theme MAIN 349:352 arg1 METHODS 354:360 MAIN METHODS 349:360 MAIN METHODS The LPS- and/or GlcN-stimulated transcriptional activities of various Gal4-binding site/TATA-box-containing reporter constructs were measured. 349:503 MAIN METHODS The LPS- and/or GlcN-stimulated transcriptional activities of various Gal4-binding site/TATA-box-containing reporter constructs were measured. 24968300 2 22 theme various 424:430 arg1 constructs 479:488 various Gal4-binding site/TATA-box-containing reporter constructs 424:488 various Gal4-binding site/TATA-box-containing reporter constructs 424:488 MAIN METHODS The LPS- and/or GlcN-stimulated transcriptional activities of various Gal4-binding site/TATA-box-containing reporter constructs were measured. 24968300 6 23 theme RNAPII 1002:1007 arg1 O-GlcNAcylation 1009:1023 RNAPII O-GlcNAcylation 1002:1023 RNAPII O-GlcNAcylation 1002:1023 In contrast, GlcN enhanced RNAPII O-GlcNAcylation, but inhibited iNOS promoter binding. 24968300 1 24 dep AIMS 145:148 arg1 is 178:179 is 178:179 is to investigate glucosamine (GlcN) as a transcriptional regulator of iNOS and other genes in association with the dynamic O-GlcNAcylation of RNA polymerase II (RNAPII) 178:346 AIMS The objective of this study is to investigate glucosamine (GlcN) as a transcriptional regulator of iNOS and other genes in association with the dynamic O-GlcNAcylation of RNA polymerase II (RNAPII). 24968300 7 25 theme basal 1080:1084 arg1 activities 1086:1095 the basal activities 1076:1095 the basal activities of reporter plasmids containing activator protein 1 (AP1), E2F, or cyclic AMP response element (CRE) binding sites 1076:1210 Furthermore, the basal activities of reporter plasmids containing activator protein 1 (AP1), E2F, or cyclic AMP response element (CRE) binding sites were consistently inhibited by GlcN in a dose-dependent manner. 24968300 9 26 theme factor 1466:1471 arg1 TGF-α 1480:1484 TGF-α 1480:1484 TGF-α 1480:1484 The transcriptional activity of transforming growth factor alpha (TGF-α) was slightly increased by both LPS and GlcN. 24968300 9 26 theme factor 1466:1471 arg1 alpha 1473:1477 transforming growth factor alpha 1446:1477 transforming growth factor alpha (TGF-α) 1446:1485 The transcriptional activity of transforming growth factor alpha (TGF-α) was slightly increased by both LPS and GlcN. 24968300 0 27 theme Basal 0:4 arg1 transcription 6:18 Basal transcription 0:18 Basal transcription 0:18 Basal transcription is regulated by lipopolysaccharide and glucosamine via the regulation of DNA binding of RNA polymerase II in RAW264.7 cells. 24968300 1 28 theme iNOS 249:252 arg1 genes 264:268 other genes 258:268 other genes in association with the dynamic O-GlcNAcylation of RNA polymerase II (RNAPII) 258:346 AIMS The objective of this study is to investigate glucosamine (GlcN) as a transcriptional regulator of iNOS and other genes in association with the dynamic O-GlcNAcylation of RNA polymerase II (RNAPII). 24968300 1 28 theme iNOS 249:252 arg1 regulator 236:244 a transcriptional regulator 218:244 a transcriptional regulator of iNOS 218:252 AIMS The objective of this study is to investigate glucosamine (GlcN) as a transcriptional regulator of iNOS and other genes in association with the dynamic O-GlcNAcylation of RNA polymerase II (RNAPII). 24968300 1 28 theme iNOS 249:252 arg1 glucosamine 196:206 glucosamine 196:206 glucosamine (GlcN) 196:213 AIMS The objective of this study is to investigate glucosamine (GlcN) as a transcriptional regulator of iNOS and other genes in association with the dynamic O-GlcNAcylation of RNA polymerase II (RNAPII). 24968300 7 29 theme activator 1129:1137 arg1 protein 1139:1145 activator protein 1 1129:1147 activator protein 1 (AP1) 1129:1153 Furthermore, the basal activities of reporter plasmids containing activator protein 1 (AP1), E2F, or cyclic AMP response element (CRE) binding sites were consistently inhibited by GlcN in a dose-dependent manner. 24968300 7 29 theme activator 1129:1137 arg1 AP1 1150:1152 AP1 1150:1152 AP1 1150:1152 Furthermore, the basal activities of reporter plasmids containing activator protein 1 (AP1), E2F, or cyclic AMP response element (CRE) binding sites were consistently inhibited by GlcN in a dose-dependent manner. 24968300 3 30 theme nitric 584:589 arg1 iNOS 607:610 iNOS 607:610 iNOS 607:610 KEY FINDINGS Basal transcriptional activities of nuclear factor-κB (NF-κB) and nitric oxide synthase (iNOS) reporter plasmids are inhibited by GlcN in RAW264.7 cells. 24968300 3 30 theme nitric 584:589 arg1 synthase 597:604 nitric oxide synthase 584:604 nitric oxide synthase (iNOS) 584:611 KEY FINDINGS Basal transcriptional activities of nuclear factor-κB (NF-κB) and nitric oxide synthase (iNOS) reporter plasmids are inhibited by GlcN in RAW264.7 cells. 24968300 4 31 theme Gal4-binding 767:778 arg1 constructs 814:823 Gal4-binding site/TATA-box-containing reporter constructs 767:823 Gal4-binding site/TATA-box-containing reporter constructs 767:823 Furthermore, GlcN suppressed whereas lipopolysaccharide (LPS) stimulated the basal activity of Gal4-binding site/TATA-box-containing reporter constructs. 24968300 1 32 theme study 172:176 arg1 objective 154:162 The objective 150:162 The objective of this study 150:176 AIMS The objective of this study is to investigate glucosamine (GlcN) as a transcriptional regulator of iNOS and other genes in association with the dynamic O-GlcNAcylation of RNA polymerase II (RNAPII). 24968300 7 33 theme AMP 1171:1173 arg1 CRE 1193:1195 CRE 1193:1195 CRE 1193:1195 Furthermore, the basal activities of reporter plasmids containing activator protein 1 (AP1), E2F, or cyclic AMP response element (CRE) binding sites were consistently inhibited by GlcN in a dose-dependent manner. 24968300 7 33 theme AMP 1171:1173 arg1 element 1184:1190 cyclic AMP response element 1164:1190 cyclic AMP response element (CRE) binding sites 1164:1210 Furthermore, the basal activities of reporter plasmids containing activator protein 1 (AP1), E2F, or cyclic AMP response element (CRE) binding sites were consistently inhibited by GlcN in a dose-dependent manner. 24968300 5 34 theme O-linked 842:849 arg1 N-acetylglucosamine 851:869 the O-linked N-acetylglucosamine 838:869 the O-linked N-acetylglucosamine modification (O-GlcNAcylation) of RNAPII 838:910 LPS reduced the O-linked N-acetylglucosamine modification (O-GlcNAcylation) of RNAPII, but enhanced the binding of this enzyme to the iNOS promoter. 24968300 5 34 theme O-linked 842:849 arg1 O-GlcNAcylation 885:899 O-GlcNAcylation 885:899 O-GlcNAcylation 885:899 LPS reduced the O-linked N-acetylglucosamine modification (O-GlcNAcylation) of RNAPII, but enhanced the binding of this enzyme to the iNOS promoter. 24968300 1 35 from regulator 236:244 arg1 association 273:283 association 273:283 association with the dynamic O-GlcNAcylation of RNA polymerase II (RNAPII) 273:346 AIMS The objective of this study is to investigate glucosamine (GlcN) as a transcriptional regulator of iNOS and other genes in association with the dynamic O-GlcNAcylation of RNA polymerase II (RNAPII). 24968300 8 36 theme CRE 1409:1411 arg1 activities 1387:1396 forskolin-induced transcriptional activities 1353:1396 forskolin-induced transcriptional activities of AP1 and CRE 1353:1411 However, GlcN did not inhibit the phorbol 12-myristate 13-acetate- (PMA-) or forskolin-induced transcriptional activities of AP1 and CRE. 24968300 8 36 theme CRE 1409:1411 arg1 PMA- 1344:1347 PMA- 1344:1347 PMA- 1344:1347 However, GlcN did not inhibit the phorbol 12-myristate 13-acetate- (PMA-) or forskolin-induced transcriptional activities of AP1 and CRE. 24968300 8 36 theme CRE 1409:1411 arg1 13-acetate- 1331:1341 the phorbol 12-myristate 13-acetate- 1306:1341 the phorbol 12-myristate 13-acetate- (PMA-) 1306:1348 However, GlcN did not inhibit the phorbol 12-myristate 13-acetate- (PMA-) or forskolin-induced transcriptional activities of AP1 and CRE. 24968300 8 37 theme 12-myristate 1318:1329 arg1 PMA- 1344:1347 PMA- 1344:1347 PMA- 1344:1347 However, GlcN did not inhibit the phorbol 12-myristate 13-acetate- (PMA-) or forskolin-induced transcriptional activities of AP1 and CRE. 24968300 8 37 theme 12-myristate 1318:1329 arg1 13-acetate- 1331:1341 the phorbol 12-myristate 13-acetate- 1306:1341 the phorbol 12-myristate 13-acetate- (PMA-) 1306:1348 However, GlcN did not inhibit the phorbol 12-myristate 13-acetate- (PMA-) or forskolin-induced transcriptional activities of AP1 and CRE. 24968300 9 38 theme transforming 1446:1457 arg1 TGF-α 1480:1484 TGF-α 1480:1484 TGF-α 1480:1484 The transcriptional activity of transforming growth factor alpha (TGF-α) was slightly increased by both LPS and GlcN. 24968300 9 38 theme transforming 1446:1457 arg1 alpha 1473:1477 transforming growth factor alpha 1446:1477 transforming growth factor alpha (TGF-α) 1446:1485 The transcriptional activity of transforming growth factor alpha (TGF-α) was slightly increased by both LPS and GlcN. 24968300 2 39 theme GlcN-stimulated 378:392 arg1 activities 410:419 The LPS- and/or GlcN-stimulated transcriptional activities 362:419 activities 410:419 MAIN METHODS The LPS- and/or GlcN-stimulated transcriptional activities of various Gal4-binding site/TATA-box-containing reporter constructs were measured. 24968300 2 40 theme transcriptional 394:408 arg1 activities 410:419 The LPS- and/or GlcN-stimulated transcriptional activities 362:419 activities 410:419 MAIN METHODS The LPS- and/or GlcN-stimulated transcriptional activities of various Gal4-binding site/TATA-box-containing reporter constructs were measured. 24968300 1 41 theme other 258:262 arg1 genes 264:268 other genes 258:268 other genes in association with the dynamic O-GlcNAcylation of RNA polymerase II (RNAPII) 258:346 AIMS The objective of this study is to investigate glucosamine (GlcN) as a transcriptional regulator of iNOS and other genes in association with the dynamic O-GlcNAcylation of RNA polymerase II (RNAPII). 24968300 1 41 theme other 258:262 arg1 glucosamine 196:206 glucosamine 196:206 glucosamine (GlcN) 196:213 AIMS The objective of this study is to investigate glucosamine (GlcN) as a transcriptional regulator of iNOS and other genes in association with the dynamic O-GlcNAcylation of RNA polymerase II (RNAPII). 24968300 0 42 theme polymerase 112:121 arg1 binding 97:103 DNA binding 93:103 DNA binding of RNA polymerase II 93:124 Basal transcription is regulated by lipopolysaccharide and glucosamine via the regulation of DNA binding of RNA polymerase II in RAW264.7 cells. 24968300 4 43 theme basal 749:753 arg1 activity 755:762 the basal activity 745:762 the basal activity of Gal4-binding site/TATA-box-containing reporter constructs 745:823 Furthermore, GlcN suppressed whereas lipopolysaccharide (LPS) stimulated the basal activity of Gal4-binding site/TATA-box-containing reporter constructs. 24968300 8 44 theme phorbol 1310:1316 arg1 PMA- 1344:1347 PMA- 1344:1347 PMA- 1344:1347 However, GlcN did not inhibit the phorbol 12-myristate 13-acetate- (PMA-) or forskolin-induced transcriptional activities of AP1 and CRE. 24968300 8 44 theme phorbol 1310:1316 arg1 13-acetate- 1331:1341 the phorbol 12-myristate 13-acetate- 1306:1341 the phorbol 12-myristate 13-acetate- (PMA-) 1306:1348 However, GlcN did not inhibit the phorbol 12-myristate 13-acetate- (PMA-) or forskolin-induced transcriptional activities of AP1 and CRE. 24968300 2 45 theme constructs 479:488 arg1 LPS- 366:369 The LPS- and/or GlcN-stimulated transcriptional activities 362:419 LPS- 366:369 MAIN METHODS The LPS- and/or GlcN-stimulated transcriptional activities of various Gal4-binding site/TATA-box-containing reporter constructs were measured. 24968300 10 46 theme DNA 1713:1715 arg1 binding 1717:1723 DNA binding 1713:1723 DNA binding 1713:1723 SIGNIFICANCE In conclusion, our data demonstrate that LPS activates, whereas GlcN suppresses, basal activities of transcription through the regulation of RNAPII O-GlcNAcylation and DNA binding. 24968300 0 47 theme RAW264.7 129:136 arg1 cells 138:142 RAW264.7 cells 129:142 RAW264.7 cells 129:142 Basal transcription is regulated by lipopolysaccharide and glucosamine via the regulation of DNA binding of RNA polymerase II in RAW264.7 cells. 24968300 0 48 from regulation 79:88 arg1 cells 138:142 RAW264.7 cells 129:142 RAW264.7 cells 129:142 Basal transcription is regulated by lipopolysaccharide and glucosamine via the regulation of DNA binding of RNA polymerase II in RAW264.7 cells. 24968300 9 49 theme alpha 1473:1477 arg1 activity 1434:1441 The transcriptional activity 1414:1441 The transcriptional activity of transforming growth factor alpha (TGF-α) 1414:1485 The transcriptional activity of transforming growth factor alpha (TGF-α) was slightly increased by both LPS and GlcN. 24968300 2 50 theme reporter 470:477 arg1 constructs 479:488 various Gal4-binding site/TATA-box-containing reporter constructs 424:488 various Gal4-binding site/TATA-box-containing reporter constructs 424:488 MAIN METHODS The LPS- and/or GlcN-stimulated transcriptional activities of various Gal4-binding site/TATA-box-containing reporter constructs were measured. 24968300 7 51 theme cyclic 1164:1169 arg1 CRE 1193:1195 CRE 1193:1195 CRE 1193:1195 Furthermore, the basal activities of reporter plasmids containing activator protein 1 (AP1), E2F, or cyclic AMP response element (CRE) binding sites were consistently inhibited by GlcN in a dose-dependent manner. 24968300 7 51 theme cyclic 1164:1169 arg1 element 1184:1190 cyclic AMP response element 1164:1190 cyclic AMP response element (CRE) binding sites 1164:1210 Furthermore, the basal activities of reporter plasmids containing activator protein 1 (AP1), E2F, or cyclic AMP response element (CRE) binding sites were consistently inhibited by GlcN in a dose-dependent manner. 24968300 8 52 theme AP1 1401:1403 arg1 activities 1387:1396 forskolin-induced transcriptional activities 1353:1396 forskolin-induced transcriptional activities of AP1 and CRE 1353:1411 However, GlcN did not inhibit the phorbol 12-myristate 13-acetate- (PMA-) or forskolin-induced transcriptional activities of AP1 and CRE. 24968300 8 52 theme AP1 1401:1403 arg1 PMA- 1344:1347 PMA- 1344:1347 PMA- 1344:1347 However, GlcN did not inhibit the phorbol 12-myristate 13-acetate- (PMA-) or forskolin-induced transcriptional activities of AP1 and CRE. 24968300 8 52 theme AP1 1401:1403 arg1 13-acetate- 1331:1341 the phorbol 12-myristate 13-acetate- 1306:1341 the phorbol 12-myristate 13-acetate- (PMA-) 1306:1348 However, GlcN did not inhibit the phorbol 12-myristate 13-acetate- (PMA-) or forskolin-induced transcriptional activities of AP1 and CRE. 24968300 2 53 theme site/TATA-box-containing 445:468 arg1 constructs 479:488 various Gal4-binding site/TATA-box-containing reporter constructs 424:488 various Gal4-binding site/TATA-box-containing reporter constructs 424:488 MAIN METHODS The LPS- and/or GlcN-stimulated transcriptional activities of various Gal4-binding site/TATA-box-containing reporter constructs were measured. 24968300 7 54 theme binding 1198:1204 arg1 sites 1206:1210 cyclic AMP response element (CRE) binding sites 1164:1210 cyclic AMP response element (CRE) binding sites 1164:1210 Furthermore, the basal activities of reporter plasmids containing activator protein 1 (AP1), E2F, or cyclic AMP response element (CRE) binding sites were consistently inhibited by GlcN in a dose-dependent manner. 24968300 8 55 theme transcriptional 1371:1385 arg1 activities 1387:1396 forskolin-induced transcriptional activities 1353:1396 forskolin-induced transcriptional activities of AP1 and CRE 1353:1411 However, GlcN did not inhibit the phorbol 12-myristate 13-acetate- (PMA-) or forskolin-induced transcriptional activities of AP1 and CRE. 24968300 3 56 theme oxide 591:595 arg1 iNOS 607:610 iNOS 607:610 iNOS 607:610 KEY FINDINGS Basal transcriptional activities of nuclear factor-κB (NF-κB) and nitric oxide synthase (iNOS) reporter plasmids are inhibited by GlcN in RAW264.7 cells. 24968300 3 56 theme oxide 591:595 arg1 synthase 597:604 nitric oxide synthase 584:604 nitric oxide synthase (iNOS) 584:611 KEY FINDINGS Basal transcriptional activities of nuclear factor-κB (NF-κB) and nitric oxide synthase (iNOS) reporter plasmids are inhibited by GlcN in RAW264.7 cells. 24968300 8 57 theme forskolin-induced 1353:1369 arg1 activities 1387:1396 forskolin-induced transcriptional activities 1353:1396 forskolin-induced transcriptional activities of AP1 and CRE 1353:1411 However, GlcN did not inhibit the phorbol 12-myristate 13-acetate- (PMA-) or forskolin-induced transcriptional activities of AP1 and CRE. 24968300 5 58 theme enzyme 946:951 arg1 binding 930:936 the binding 926:936 the binding of this enzyme to the iNOS promoter 926:972 LPS reduced the O-linked N-acetylglucosamine modification (O-GlcNAcylation) of RNAPII, but enhanced the binding of this enzyme to the iNOS promoter. 24968300 2 59 theme Gal4-binding 432:443 arg1 constructs 479:488 various Gal4-binding site/TATA-box-containing reporter constructs 424:488 various Gal4-binding site/TATA-box-containing reporter constructs 424:488 MAIN METHODS The LPS- and/or GlcN-stimulated transcriptional activities of various Gal4-binding site/TATA-box-containing reporter constructs were measured. 24968300 7 60 theme reporter 1100:1107 arg1 plasmids 1109:1116 reporter plasmids 1100:1116 reporter plasmids containing activator protein 1 (AP1), E2F, or cyclic AMP response element (CRE) binding sites 1100:1210 Furthermore, the basal activities of reporter plasmids containing activator protein 1 (AP1), E2F, or cyclic AMP response element (CRE) binding sites were consistently inhibited by GlcN in a dose-dependent manner. 24968300 3 61 theme synthase 597:604 arg1 plasmids 622:629 nuclear factor-κB (NF-κB) and nitric oxide synthase (iNOS) reporter plasmids 554:629 nuclear factor-κB (NF-κB) and nitric oxide synthase (iNOS) reporter plasmids 554:629 KEY FINDINGS Basal transcriptional activities of nuclear factor-κB (NF-κB) and nitric oxide synthase (iNOS) reporter plasmids are inhibited by GlcN in RAW264.7 cells. 24968300 3 62 theme KEY 505:507 arg1 activities 540:549 KEY FINDINGS Basal transcriptional activities 505:549 KEY FINDINGS Basal transcriptional activities of nuclear factor-κB (NF-κB) and nitric oxide synthase (iNOS) reporter plasmids 505:629 KEY FINDINGS Basal transcriptional activities of nuclear factor-κB (NF-κB) and nitric oxide synthase (iNOS) reporter plasmids are inhibited by GlcN in RAW264.7 cells. 24968300 5 63 link O-linked 842:849 arg1 N-acetylglucosamine 851:869 the O-linked N-acetylglucosamine 838:869 the O-linked N-acetylglucosamine modification (O-GlcNAcylation) of RNAPII 838:910 LPS reduced the O-linked N-acetylglucosamine modification (O-GlcNAcylation) of RNAPII, but enhanced the binding of this enzyme to the iNOS promoter. 24968300 5 63 link O-linked 842:849 arg1 O-GlcNAcylation 885:899 O-GlcNAcylation 885:899 O-GlcNAcylation 885:899 LPS reduced the O-linked N-acetylglucosamine modification (O-GlcNAcylation) of RNAPII, but enhanced the binding of this enzyme to the iNOS promoter. 24968300 10 64 theme basal 1626:1630 arg1 activities 1632:1641 basal activities 1626:1641 basal activities of transcription 1626:1658 SIGNIFICANCE In conclusion, our data demonstrate that LPS activates, whereas GlcN suppresses, basal activities of transcription through the regulation of RNAPII O-GlcNAcylation and DNA binding. 24968300 3 65 theme plasmids 622:629 arg1 activities 540:549 KEY FINDINGS Basal transcriptional activities 505:549 KEY FINDINGS Basal transcriptional activities of nuclear factor-κB (NF-κB) and nitric oxide synthase (iNOS) reporter plasmids 505:629 KEY FINDINGS Basal transcriptional activities of nuclear factor-κB (NF-κB) and nitric oxide synthase (iNOS) reporter plasmids are inhibited by GlcN in RAW264.7 cells. 24968300 7 66 theme dose-dependent 1253:1266 arg1 manner 1268:1273 a dose-dependent manner 1251:1273 a dose-dependent manner 1251:1273 Furthermore, the basal activities of reporter plasmids containing activator protein 1 (AP1), E2F, or cyclic AMP response element (CRE) binding sites were consistently inhibited by GlcN in a dose-dependent manner. 24968300 7 67 contain containing 1118:1127 arg2 E2F 1156:1158 E2F 1156:1158 E2F 1156:1158 Furthermore, the basal activities of reporter plasmids containing activator protein 1 (AP1), E2F, or cyclic AMP response element (CRE) binding sites were consistently inhibited by GlcN in a dose-dependent manner. 24968300 7 67 contain containing 1118:1127 arg2 AP1 1150:1152 AP1 1150:1152 AP1 1150:1152 Furthermore, the basal activities of reporter plasmids containing activator protein 1 (AP1), E2F, or cyclic AMP response element (CRE) binding sites were consistently inhibited by GlcN in a dose-dependent manner. 24968300 7 67 contain containing 1118:1127 arg2 protein 1139:1145 activator protein 1 1129:1147 activator protein 1 (AP1) 1129:1153 Furthermore, the basal activities of reporter plasmids containing activator protein 1 (AP1), E2F, or cyclic AMP response element (CRE) binding sites were consistently inhibited by GlcN in a dose-dependent manner. 24968300 7 67 contain containing 1118:1127 arg2 sites 1206:1210 cyclic AMP response element (CRE) binding sites 1164:1210 cyclic AMP response element (CRE) binding sites 1164:1210 Furthermore, the basal activities of reporter plasmids containing activator protein 1 (AP1), E2F, or cyclic AMP response element (CRE) binding sites were consistently inhibited by GlcN in a dose-dependent manner. 24968300 7 67 contain containing 1118:1127 arg1 plasmids 1109:1116 reporter plasmids 1100:1116 reporter plasmids containing activator protein 1 (AP1), E2F, or cyclic AMP response element (CRE) binding sites 1100:1210 Furthermore, the basal activities of reporter plasmids containing activator protein 1 (AP1), E2F, or cyclic AMP response element (CRE) binding sites were consistently inhibited by GlcN in a dose-dependent manner. 24968300 4 68 theme site/TATA-box-containing 780:803 arg1 constructs 814:823 Gal4-binding site/TATA-box-containing reporter constructs 767:823 Gal4-binding site/TATA-box-containing reporter constructs 767:823 Furthermore, GlcN suppressed whereas lipopolysaccharide (LPS) stimulated the basal activity of Gal4-binding site/TATA-box-containing reporter constructs. 24968300 3 69 theme RAW264.7 656:663 arg1 cells 665:669 RAW264.7 cells 656:669 RAW264.7 cells 656:669 KEY FINDINGS Basal transcriptional activities of nuclear factor-κB (NF-κB) and nitric oxide synthase (iNOS) reporter plasmids are inhibited by GlcN in RAW264.7 cells. 24968300 4 70 theme constructs 814:823 arg1 activity 755:762 the basal activity 745:762 the basal activity of Gal4-binding site/TATA-box-containing reporter constructs 745:823 Furthermore, GlcN suppressed whereas lipopolysaccharide (LPS) stimulated the basal activity of Gal4-binding site/TATA-box-containing reporter constructs. 24968300 10 71 dep SIGNIFICANCE 1532:1543 arg1 conclusion 1548:1557 conclusion 1548:1557 conclusion 1548:1557 SIGNIFICANCE In conclusion, our data demonstrate that LPS activates, whereas GlcN suppresses, basal activities of transcription through the regulation of RNAPII O-GlcNAcylation and DNA binding. 24968300 5 72 theme iNOS 960:963 arg1 promoter 965:972 the iNOS promoter 956:972 the iNOS promoter 956:972 LPS reduced the O-linked N-acetylglucosamine modification (O-GlcNAcylation) of RNAPII, but enhanced the binding of this enzyme to the iNOS promoter. 24968300 2 73 dep METHODS 354:360 arg1 measured 495:502 measured 495:502 were measured 490:502 MAIN METHODS The LPS- and/or GlcN-stimulated transcriptional activities of various Gal4-binding site/TATA-box-containing reporter constructs were measured. 24968300 10 74 theme RNAPII 1686:1691 arg1 O-GlcNAcylation 1693:1707 RNAPII O-GlcNAcylation 1686:1707 RNAPII O-GlcNAcylation 1686:1707 SIGNIFICANCE In conclusion, our data demonstrate that LPS activates, whereas GlcN suppresses, basal activities of transcription through the regulation of RNAPII O-GlcNAcylation and DNA binding. 24968300 3 75 theme transcriptional 524:538 arg1 activities 540:549 KEY FINDINGS Basal transcriptional activities 505:549 KEY FINDINGS Basal transcriptional activities of nuclear factor-κB (NF-κB) and nitric oxide synthase (iNOS) reporter plasmids 505:629 KEY FINDINGS Basal transcriptional activities of nuclear factor-κB (NF-κB) and nitric oxide synthase (iNOS) reporter plasmids are inhibited by GlcN in RAW264.7 cells. 24968300 9 76 theme growth 1459:1464 arg1 TGF-α 1480:1484 TGF-α 1480:1484 TGF-α 1480:1484 The transcriptional activity of transforming growth factor alpha (TGF-α) was slightly increased by both LPS and GlcN. 24968300 9 76 theme growth 1459:1464 arg1 alpha 1473:1477 transforming growth factor alpha 1446:1477 transforming growth factor alpha (TGF-α) 1446:1485 The transcriptional activity of transforming growth factor alpha (TGF-α) was slightly increased by both LPS and GlcN. 24968300 6 77 theme promoter 1045:1052 arg1 binding 1054:1060 iNOS promoter binding 1040:1060 iNOS promoter binding 1040:1060 In contrast, GlcN enhanced RNAPII O-GlcNAcylation, but inhibited iNOS promoter binding. 24968300 1 78 theme dynamic 294:300 arg1 O-GlcNAcylation 302:316 the dynamic O-GlcNAcylation 290:316 the dynamic O-GlcNAcylation of RNA polymerase II (RNAPII) 290:346 AIMS The objective of this study is to investigate glucosamine (GlcN) as a transcriptional regulator of iNOS and other genes in association with the dynamic O-GlcNAcylation of RNA polymerase II (RNAPII). 24968300 3 79 theme reporter 613:620 arg1 plasmids 622:629 nuclear factor-κB (NF-κB) and nitric oxide synthase (iNOS) reporter plasmids 554:629 nuclear factor-κB (NF-κB) and nitric oxide synthase (iNOS) reporter plasmids 554:629 KEY FINDINGS Basal transcriptional activities of nuclear factor-κB (NF-κB) and nitric oxide synthase (iNOS) reporter plasmids are inhibited by GlcN in RAW264.7 cells. 24968300 7 80 theme element 1184:1190 arg1 sites 1206:1210 cyclic AMP response element (CRE) binding sites 1164:1210 cyclic AMP response element (CRE) binding sites 1164:1210 Furthermore, the basal activities of reporter plasmids containing activator protein 1 (AP1), E2F, or cyclic AMP response element (CRE) binding sites were consistently inhibited by GlcN in a dose-dependent manner. 24968300 6 81 theme iNOS 1040:1043 arg1 binding 1054:1060 iNOS promoter binding 1040:1060 iNOS promoter binding 1040:1060 In contrast, GlcN enhanced RNAPII O-GlcNAcylation, but inhibited iNOS promoter binding. 23860037 5 0 theme factor-like 1023:1033 arg1 proteins 1053:1060 epidermal growth factor-like domain-containing proteins 1006:1060 epidermal growth factor-like domain-containing proteins 1006:1060 EOGT encodes EGF-domain-specific O-linked N-acetylglucosamine transferase, responsible for extracellular O-GlcNAcylation of epidermal growth factor-like domain-containing proteins, and is essential for epithelial cell-matrix interactions. 23860037 5 1 theme cell-matrix 1095:1105 arg1 interactions 1107:1118 epithelial cell-matrix interactions 1084:1118 epithelial cell-matrix interactions 1084:1118 EOGT encodes EGF-domain-specific O-linked N-acetylglucosamine transferase, responsible for extracellular O-GlcNAcylation of epidermal growth factor-like domain-containing proteins, and is essential for epithelial cell-matrix interactions. 23860037 2 2 theme affected 405:412 arg1 individuals 414:424 affected individuals 405:424 affected individuals (LOD score 3.37) 405:441 Genome-wide linkage analysis ruled out association with known Adams-Oliver syndrome genes, identifying a single-homozygosity ∼1.8-Mb novel locus common to affected individuals (LOD score 3.37). 23860037 2 2 theme affected 405:412 arg1 score 431:435 LOD score 3.37 427:440 LOD score 3.37 427:440 Genome-wide linkage analysis ruled out association with known Adams-Oliver syndrome genes, identifying a single-homozygosity ∼1.8-Mb novel locus common to affected individuals (LOD score 3.37). 23860037 0 3 theme EGF 93:95 arg1 transferase 122:132 an EGF domain-specific O-GlcNAc transferase 90:132 an EGF domain-specific O-GlcNAc transferase 90:132 Autosomal recessive Adams-Oliver syndrome caused by homozygous mutation in EOGT, encoding an EGF domain-specific O-GlcNAc transferase. 23860037 3 4 theme unrelated 639:647 arg1 families 657:664 five additional apparently unrelated Bedouin families 612:664 five additional apparently unrelated Bedouin families: a 1-bp deletion mutation in a predicted alternative splice variant of EOGT 612:740 Whole-exome sequencing followed by Sanger sequencing identified only a single mutation within this locus, shared by all affected individuals and found in patients from five additional apparently unrelated Bedouin families: a 1-bp deletion mutation in a predicted alternative splice variant of EOGT, leading to a putative truncated protein. 23860037 4 5 theme alternative 828:838 arg1 variant 847:853 the EOGT-predicted alternative splice variant 809:853 the EOGT-predicted alternative splice variant 809:853 RT-PCR demonstrated that the EOGT-predicted alternative splice variant is ubiquitously expressed. 23860037 3 6 theme EOGT 737:740 arg1 variant 726:732 a predicted alternative splice variant 695:732 a predicted alternative splice variant of EOGT 695:740 Whole-exome sequencing followed by Sanger sequencing identified only a single mutation within this locus, shared by all affected individuals and found in patients from five additional apparently unrelated Bedouin families: a 1-bp deletion mutation in a predicted alternative splice variant of EOGT, leading to a putative truncated protein. 23860037 6 7 theme diseased 1141:1148 arg1 fibroblasts 1150:1160 diseased fibroblasts 1141:1160 diseased fibroblasts 1141:1160 F-actin staining in diseased fibroblasts showed apparently intact cell cytoskeleton and morphology, suggesting the EOGT mutation acts not through perturbation of cytoskeleton but through other mechanisms yet to be elucidated. 23860037 3 8 theme additional 617:626 arg1 families 657:664 five additional apparently unrelated Bedouin families 612:664 five additional apparently unrelated Bedouin families: a 1-bp deletion mutation in a predicted alternative splice variant of EOGT 612:740 Whole-exome sequencing followed by Sanger sequencing identified only a single mutation within this locus, shared by all affected individuals and found in patients from five additional apparently unrelated Bedouin families: a 1-bp deletion mutation in a predicted alternative splice variant of EOGT, leading to a putative truncated protein. 23860037 0 9 from mutation 63:70 arg1 EOGT 75:78 EOGT 75:78 EOGT 75:78 Autosomal recessive Adams-Oliver syndrome caused by homozygous mutation in EOGT, encoding an EGF domain-specific O-GlcNAc transferase. 23860037 4 10 theme EOGT-predicted 813:826 arg1 variant 847:853 the EOGT-predicted alternative splice variant 809:853 the EOGT-predicted alternative splice variant 809:853 RT-PCR demonstrated that the EOGT-predicted alternative splice variant is ubiquitously expressed. 23860037 2 11 theme novel 383:387 arg1 locus 389:393 a single-homozygosity ∼1.8-Mb novel locus 353:393 a single-homozygosity ∼1.8-Mb novel locus common to affected individuals (LOD score 3.37) 353:441 Genome-wide linkage analysis ruled out association with known Adams-Oliver syndrome genes, identifying a single-homozygosity ∼1.8-Mb novel locus common to affected individuals (LOD score 3.37). 23860037 0 12 theme O-GlcNAc 113:120 arg1 transferase 122:132 an EGF domain-specific O-GlcNAc transferase 90:132 an EGF domain-specific O-GlcNAc transferase 90:132 Autosomal recessive Adams-Oliver syndrome caused by homozygous mutation in EOGT, encoding an EGF domain-specific O-GlcNAc transferase. 23860037 6 13 theme other 1308:1312 arg1 mechanisms 1314:1323 other mechanisms 1308:1323 other mechanisms 1308:1323 F-actin staining in diseased fibroblasts showed apparently intact cell cytoskeleton and morphology, suggesting the EOGT mutation acts not through perturbation of cytoskeleton but through other mechanisms yet to be elucidated. 23860037 2 14 theme syndrome 325:332 arg1 genes 334:338 known Adams-Oliver syndrome genes 306:338 known Adams-Oliver syndrome genes 306:338 Genome-wide linkage analysis ruled out association with known Adams-Oliver syndrome genes, identifying a single-homozygosity ∼1.8-Mb novel locus common to affected individuals (LOD score 3.37). 23860037 3 15 dep families 657:664 arg1 mutation 683:690 a 1-bp deletion mutation 667:690 five additional apparently unrelated Bedouin families: a 1-bp deletion mutation in a predicted alternative splice variant of EOGT 612:740 Whole-exome sequencing followed by Sanger sequencing identified only a single mutation within this locus, shared by all affected individuals and found in patients from five additional apparently unrelated Bedouin families: a 1-bp deletion mutation in a predicted alternative splice variant of EOGT, leading to a putative truncated protein. 23860037 0 16 theme domain-specific 97:111 arg1 transferase 122:132 an EGF domain-specific O-GlcNAc transferase 90:132 an EGF domain-specific O-GlcNAc transferase 90:132 Autosomal recessive Adams-Oliver syndrome caused by homozygous mutation in EOGT, encoding an EGF domain-specific O-GlcNAc transferase. 23860037 3 17 theme putative 756:763 arg1 protein 775:781 a putative truncated protein 754:781 a putative truncated protein 754:781 Whole-exome sequencing followed by Sanger sequencing identified only a single mutation within this locus, shared by all affected individuals and found in patients from five additional apparently unrelated Bedouin families: a 1-bp deletion mutation in a predicted alternative splice variant of EOGT, leading to a putative truncated protein. 23860037 2 18 theme Adams-Oliver 312:323 arg1 genes 334:338 known Adams-Oliver syndrome genes 306:338 known Adams-Oliver syndrome genes 306:338 Genome-wide linkage analysis ruled out association with known Adams-Oliver syndrome genes, identifying a single-homozygosity ∼1.8-Mb novel locus common to affected individuals (LOD score 3.37). 23860037 5 19 theme extracellular 973:985 arg1 O-GlcNAcylation 987:1001 extracellular O-GlcNAcylation 973:1001 extracellular O-GlcNAcylation of epidermal growth factor-like domain-containing proteins 973:1060 EOGT encodes EGF-domain-specific O-linked N-acetylglucosamine transferase, responsible for extracellular O-GlcNAcylation of epidermal growth factor-like domain-containing proteins, and is essential for epithelial cell-matrix interactions. 23860037 0 20 theme recessive 10:18 arg1 syndrome 33:40 Autosomal recessive Adams-Oliver syndrome 0:40 Autosomal recessive Adams-Oliver syndrome 0:40 Autosomal recessive Adams-Oliver syndrome caused by homozygous mutation in EOGT, encoding an EGF domain-specific O-GlcNAc transferase. 23860037 3 21 theme truncated 765:773 arg1 protein 775:781 a putative truncated protein 754:781 a putative truncated protein 754:781 Whole-exome sequencing followed by Sanger sequencing identified only a single mutation within this locus, shared by all affected individuals and found in patients from five additional apparently unrelated Bedouin families: a 1-bp deletion mutation in a predicted alternative splice variant of EOGT, leading to a putative truncated protein. 23860037 2 22 theme ∼1.8-Mb 375:381 arg1 locus 389:393 a single-homozygosity ∼1.8-Mb novel locus 353:393 a single-homozygosity ∼1.8-Mb novel locus common to affected individuals (LOD score 3.37) 353:441 Genome-wide linkage analysis ruled out association with known Adams-Oliver syndrome genes, identifying a single-homozygosity ∼1.8-Mb novel locus common to affected individuals (LOD score 3.37). 23860037 3 23 theme affected 564:571 arg1 individuals 573:583 all affected individuals 560:583 all affected individuals 560:583 Whole-exome sequencing followed by Sanger sequencing identified only a single mutation within this locus, shared by all affected individuals and found in patients from five additional apparently unrelated Bedouin families: a 1-bp deletion mutation in a predicted alternative splice variant of EOGT, leading to a putative truncated protein. 23860037 3 24 theme Sanger 479:484 arg1 sequencing 486:495 Sanger sequencing 479:495 Sanger sequencing 479:495 Whole-exome sequencing followed by Sanger sequencing identified only a single mutation within this locus, shared by all affected individuals and found in patients from five additional apparently unrelated Bedouin families: a 1-bp deletion mutation in a predicted alternative splice variant of EOGT, leading to a putative truncated protein. 23860037 0 25 theme Autosomal 0:8 arg1 syndrome 33:40 Autosomal recessive Adams-Oliver syndrome 0:40 Autosomal recessive Adams-Oliver syndrome 0:40 Autosomal recessive Adams-Oliver syndrome caused by homozygous mutation in EOGT, encoding an EGF domain-specific O-GlcNAc transferase. 23860037 2 26 theme single-homozygosity 355:373 arg1 locus 389:393 a single-homozygosity ∼1.8-Mb novel locus 353:393 a single-homozygosity ∼1.8-Mb novel locus common to affected individuals (LOD score 3.37) 353:441 Genome-wide linkage analysis ruled out association with known Adams-Oliver syndrome genes, identifying a single-homozygosity ∼1.8-Mb novel locus common to affected individuals (LOD score 3.37). 23860037 1 27 theme related 209:215 arg1 families 240:247 three remotely related Bedouin consanguineous families 194:247 three remotely related Bedouin consanguineous families 194:247 Autosomal recessive Adams-Oliver syndrome was diagnosed in three remotely related Bedouin consanguineous families. 23860037 5 28 theme EGF-domain-specific 895:913 arg1 transferase 944:954 EGF-domain-specific O-linked N-acetylglucosamine transferase 895:954 EGF-domain-specific O-linked N-acetylglucosamine transferase 895:954 EOGT encodes EGF-domain-specific O-linked N-acetylglucosamine transferase, responsible for extracellular O-GlcNAcylation of epidermal growth factor-like domain-containing proteins, and is essential for epithelial cell-matrix interactions. 23860037 5 28 theme EGF-domain-specific 895:913 arg1 EOGT 882:885 EOGT 882:885 EOGT 882:885 EOGT encodes EGF-domain-specific O-linked N-acetylglucosamine transferase, responsible for extracellular O-GlcNAcylation of epidermal growth factor-like domain-containing proteins, and is essential for epithelial cell-matrix interactions. 23860037 6 29 theme F-actin 1121:1127 arg1 staining 1129:1136 F-actin staining 1121:1136 F-actin staining in diseased fibroblasts 1121:1160 F-actin staining in diseased fibroblasts showed apparently intact cell cytoskeleton and morphology, suggesting the EOGT mutation acts not through perturbation of cytoskeleton but through other mechanisms yet to be elucidated. 23860037 3 30 theme Bedouin 649:655 arg1 families 657:664 five additional apparently unrelated Bedouin families 612:664 five additional apparently unrelated Bedouin families: a 1-bp deletion mutation in a predicted alternative splice variant of EOGT 612:740 Whole-exome sequencing followed by Sanger sequencing identified only a single mutation within this locus, shared by all affected individuals and found in patients from five additional apparently unrelated Bedouin families: a 1-bp deletion mutation in a predicted alternative splice variant of EOGT, leading to a putative truncated protein. 23860037 5 31 theme epithelial 1084:1093 arg1 interactions 1107:1118 epithelial cell-matrix interactions 1084:1118 epithelial cell-matrix interactions 1084:1118 EOGT encodes EGF-domain-specific O-linked N-acetylglucosamine transferase, responsible for extracellular O-GlcNAcylation of epidermal growth factor-like domain-containing proteins, and is essential for epithelial cell-matrix interactions. 23860037 3 32 from mutation 683:690 arg1 variant 726:732 a predicted alternative splice variant 695:732 a predicted alternative splice variant of EOGT 695:740 Whole-exome sequencing followed by Sanger sequencing identified only a single mutation within this locus, shared by all affected individuals and found in patients from five additional apparently unrelated Bedouin families: a 1-bp deletion mutation in a predicted alternative splice variant of EOGT, leading to a putative truncated protein. 23860037 1 33 theme Bedouin 217:223 arg1 families 240:247 three remotely related Bedouin consanguineous families 194:247 three remotely related Bedouin consanguineous families 194:247 Autosomal recessive Adams-Oliver syndrome was diagnosed in three remotely related Bedouin consanguineous families. 23860037 0 34 theme Adams-Oliver 20:31 arg1 syndrome 33:40 Autosomal recessive Adams-Oliver syndrome 0:40 Autosomal recessive Adams-Oliver syndrome 0:40 Autosomal recessive Adams-Oliver syndrome caused by homozygous mutation in EOGT, encoding an EGF domain-specific O-GlcNAc transferase. 23860037 3 35 theme predicted 697:705 arg1 variant 726:732 a predicted alternative splice variant 695:732 a predicted alternative splice variant of EOGT 695:740 Whole-exome sequencing followed by Sanger sequencing identified only a single mutation within this locus, shared by all affected individuals and found in patients from five additional apparently unrelated Bedouin families: a 1-bp deletion mutation in a predicted alternative splice variant of EOGT, leading to a putative truncated protein. 23860037 5 36 theme domain-containing 1035:1051 arg1 proteins 1053:1060 epidermal growth factor-like domain-containing proteins 1006:1060 epidermal growth factor-like domain-containing proteins 1006:1060 EOGT encodes EGF-domain-specific O-linked N-acetylglucosamine transferase, responsible for extracellular O-GlcNAcylation of epidermal growth factor-like domain-containing proteins, and is essential for epithelial cell-matrix interactions. 23860037 3 37 from families 657:664 arg1 patients 598:605 patients 598:605 patients from five additional apparently unrelated Bedouin families: a 1-bp deletion mutation in a predicted alternative splice variant of EOGT 598:740 Whole-exome sequencing followed by Sanger sequencing identified only a single mutation within this locus, shared by all affected individuals and found in patients from five additional apparently unrelated Bedouin families: a 1-bp deletion mutation in a predicted alternative splice variant of EOGT, leading to a putative truncated protein. 23860037 1 38 theme consanguineous 225:238 arg1 families 240:247 three remotely related Bedouin consanguineous families 194:247 three remotely related Bedouin consanguineous families 194:247 Autosomal recessive Adams-Oliver syndrome was diagnosed in three remotely related Bedouin consanguineous families. 23860037 3 39 theme deletion 674:681 arg1 mutation 683:690 a 1-bp deletion mutation 667:690 five additional apparently unrelated Bedouin families: a 1-bp deletion mutation in a predicted alternative splice variant of EOGT 612:740 Whole-exome sequencing followed by Sanger sequencing identified only a single mutation within this locus, shared by all affected individuals and found in patients from five additional apparently unrelated Bedouin families: a 1-bp deletion mutation in a predicted alternative splice variant of EOGT, leading to a putative truncated protein. 23860037 6 40 from staining 1129:1136 arg1 fibroblasts 1150:1160 diseased fibroblasts 1141:1160 diseased fibroblasts 1141:1160 F-actin staining in diseased fibroblasts showed apparently intact cell cytoskeleton and morphology, suggesting the EOGT mutation acts not through perturbation of cytoskeleton but through other mechanisms yet to be elucidated. 23860037 3 41 theme alternative 707:717 arg1 variant 726:732 a predicted alternative splice variant 695:732 a predicted alternative splice variant of EOGT 695:740 Whole-exome sequencing followed by Sanger sequencing identified only a single mutation within this locus, shared by all affected individuals and found in patients from five additional apparently unrelated Bedouin families: a 1-bp deletion mutation in a predicted alternative splice variant of EOGT, leading to a putative truncated protein. 23860037 6 42 theme EOGT 1236:1239 arg1 mutation 1241:1248 the EOGT mutation 1232:1248 the EOGT mutation 1232:1248 F-actin staining in diseased fibroblasts showed apparently intact cell cytoskeleton and morphology, suggesting the EOGT mutation acts not through perturbation of cytoskeleton but through other mechanisms yet to be elucidated. 23860037 2 43 with association 289:299 arg1 genes 334:338 known Adams-Oliver syndrome genes 306:338 known Adams-Oliver syndrome genes 306:338 Genome-wide linkage analysis ruled out association with known Adams-Oliver syndrome genes, identifying a single-homozygosity ∼1.8-Mb novel locus common to affected individuals (LOD score 3.37). 23860037 3 44 theme single 515:520 arg1 mutation 522:529 a single mutation 513:529 a single mutation 513:529 Whole-exome sequencing followed by Sanger sequencing identified only a single mutation within this locus, shared by all affected individuals and found in patients from five additional apparently unrelated Bedouin families: a 1-bp deletion mutation in a predicted alternative splice variant of EOGT, leading to a putative truncated protein. 23860037 3 45 theme Whole-exome 444:454 arg1 sequencing 456:465 Whole-exome sequencing 444:465 Whole-exome sequencing followed by Sanger sequencing 444:495 Whole-exome sequencing followed by Sanger sequencing identified only a single mutation within this locus, shared by all affected individuals and found in patients from five additional apparently unrelated Bedouin families: a 1-bp deletion mutation in a predicted alternative splice variant of EOGT, leading to a putative truncated protein. 23860037 5 46 theme epidermal 1006:1014 arg1 growth 1016:1021 epidermal growth 1006:1021 epidermal growth factor-like domain-containing proteins 1006:1060 EOGT encodes EGF-domain-specific O-linked N-acetylglucosamine transferase, responsible for extracellular O-GlcNAcylation of epidermal growth factor-like domain-containing proteins, and is essential for epithelial cell-matrix interactions. 23860037 5 47 theme O-linked 915:922 arg1 transferase 944:954 EGF-domain-specific O-linked N-acetylglucosamine transferase 895:954 EGF-domain-specific O-linked N-acetylglucosamine transferase 895:954 EOGT encodes EGF-domain-specific O-linked N-acetylglucosamine transferase, responsible for extracellular O-GlcNAcylation of epidermal growth factor-like domain-containing proteins, and is essential for epithelial cell-matrix interactions. 23860037 5 47 theme O-linked 915:922 arg1 EOGT 882:885 EOGT 882:885 EOGT 882:885 EOGT encodes EGF-domain-specific O-linked N-acetylglucosamine transferase, responsible for extracellular O-GlcNAcylation of epidermal growth factor-like domain-containing proteins, and is essential for epithelial cell-matrix interactions. 23860037 2 48 theme linkage 262:268 arg1 analysis 270:277 Genome-wide linkage analysis 250:277 Genome-wide linkage analysis 250:277 Genome-wide linkage analysis ruled out association with known Adams-Oliver syndrome genes, identifying a single-homozygosity ∼1.8-Mb novel locus common to affected individuals (LOD score 3.37). 23860037 5 49 theme proteins 1053:1060 arg1 O-GlcNAcylation 987:1001 extracellular O-GlcNAcylation 973:1001 extracellular O-GlcNAcylation of epidermal growth factor-like domain-containing proteins 973:1060 EOGT encodes EGF-domain-specific O-linked N-acetylglucosamine transferase, responsible for extracellular O-GlcNAcylation of epidermal growth factor-like domain-containing proteins, and is essential for epithelial cell-matrix interactions. 23860037 0 50 theme homozygous 52:61 arg1 mutation 63:70 homozygous mutation 52:70 homozygous mutation 52:70 Autosomal recessive Adams-Oliver syndrome caused by homozygous mutation in EOGT, encoding an EGF domain-specific O-GlcNAc transferase. 23860037 2 51 theme Genome-wide 250:260 arg1 analysis 270:277 Genome-wide linkage analysis 250:277 Genome-wide linkage analysis 250:277 Genome-wide linkage analysis ruled out association with known Adams-Oliver syndrome genes, identifying a single-homozygosity ∼1.8-Mb novel locus common to affected individuals (LOD score 3.37). 23860037 2 52 theme common 395:400 arg1 locus 389:393 a single-homozygosity ∼1.8-Mb novel locus 353:393 a single-homozygosity ∼1.8-Mb novel locus common to affected individuals (LOD score 3.37) 353:441 Genome-wide linkage analysis ruled out association with known Adams-Oliver syndrome genes, identifying a single-homozygosity ∼1.8-Mb novel locus common to affected individuals (LOD score 3.37). 23860037 1 53 theme Adams-Oliver 155:166 arg1 syndrome 168:175 Autosomal recessive Adams-Oliver syndrome 135:175 Autosomal recessive Adams-Oliver syndrome 135:175 Autosomal recessive Adams-Oliver syndrome was diagnosed in three remotely related Bedouin consanguineous families. 23860037 2 54 theme known 306:310 arg1 genes 334:338 known Adams-Oliver syndrome genes 306:338 known Adams-Oliver syndrome genes 306:338 Genome-wide linkage analysis ruled out association with known Adams-Oliver syndrome genes, identifying a single-homozygosity ∼1.8-Mb novel locus common to affected individuals (LOD score 3.37). 23860037 1 55 theme Autosomal 135:143 arg1 syndrome 168:175 Autosomal recessive Adams-Oliver syndrome 135:175 Autosomal recessive Adams-Oliver syndrome 135:175 Autosomal recessive Adams-Oliver syndrome was diagnosed in three remotely related Bedouin consanguineous families. 23860037 6 56 theme cytoskeleton 1283:1294 arg1 perturbation 1267:1278 perturbation 1267:1278 perturbation of cytoskeleton 1267:1294 F-actin staining in diseased fibroblasts showed apparently intact cell cytoskeleton and morphology, suggesting the EOGT mutation acts not through perturbation of cytoskeleton but through other mechanisms yet to be elucidated. 23860037 4 57 theme splice 840:845 arg1 variant 847:853 the EOGT-predicted alternative splice variant 809:853 the EOGT-predicted alternative splice variant 809:853 RT-PCR demonstrated that the EOGT-predicted alternative splice variant is ubiquitously expressed. 23860037 3 58 theme splice 719:724 arg1 variant 726:732 a predicted alternative splice variant 695:732 a predicted alternative splice variant of EOGT 695:740 Whole-exome sequencing followed by Sanger sequencing identified only a single mutation within this locus, shared by all affected individuals and found in patients from five additional apparently unrelated Bedouin families: a 1-bp deletion mutation in a predicted alternative splice variant of EOGT, leading to a putative truncated protein. 23860037 5 59 link O-linked 915:922 arg1 transferase 944:954 EGF-domain-specific O-linked N-acetylglucosamine transferase 895:954 EGF-domain-specific O-linked N-acetylglucosamine transferase 895:954 EOGT encodes EGF-domain-specific O-linked N-acetylglucosamine transferase, responsible for extracellular O-GlcNAcylation of epidermal growth factor-like domain-containing proteins, and is essential for epithelial cell-matrix interactions. 23860037 5 59 link O-linked 915:922 arg1 EOGT 882:885 EOGT 882:885 EOGT 882:885 EOGT encodes EGF-domain-specific O-linked N-acetylglucosamine transferase, responsible for extracellular O-GlcNAcylation of epidermal growth factor-like domain-containing proteins, and is essential for epithelial cell-matrix interactions. 23860037 1 60 theme recessive 145:153 arg1 syndrome 168:175 Autosomal recessive Adams-Oliver syndrome 135:175 Autosomal recessive Adams-Oliver syndrome 135:175 Autosomal recessive Adams-Oliver syndrome was diagnosed in three remotely related Bedouin consanguineous families. 23860037 6 61 theme cell 1187:1190 arg1 cytoskeleton 1192:1203 apparently intact cell cytoskeleton 1169:1203 apparently intact cell cytoskeleton 1169:1203 F-actin staining in diseased fibroblasts showed apparently intact cell cytoskeleton and morphology, suggesting the EOGT mutation acts not through perturbation of cytoskeleton but through other mechanisms yet to be elucidated. 23860037 5 62 theme responsible 957:967 arg1 transferase 944:954 EGF-domain-specific O-linked N-acetylglucosamine transferase 895:954 EGF-domain-specific O-linked N-acetylglucosamine transferase 895:954 EOGT encodes EGF-domain-specific O-linked N-acetylglucosamine transferase, responsible for extracellular O-GlcNAcylation of epidermal growth factor-like domain-containing proteins, and is essential for epithelial cell-matrix interactions. 23860037 5 62 theme responsible 957:967 arg1 EOGT 882:885 EOGT 882:885 EOGT 882:885 EOGT encodes EGF-domain-specific O-linked N-acetylglucosamine transferase, responsible for extracellular O-GlcNAcylation of epidermal growth factor-like domain-containing proteins, and is essential for epithelial cell-matrix interactions. 23860037 3 63 dep mutation 522:529 arg1 shared 550:555 shared 550:555 shared by all affected individuals 550:583 Whole-exome sequencing followed by Sanger sequencing identified only a single mutation within this locus, shared by all affected individuals and found in patients from five additional apparently unrelated Bedouin families: a 1-bp deletion mutation in a predicted alternative splice variant of EOGT, leading to a putative truncated protein. 23860037 3 63 dep mutation 522:529 arg1 found 589:593 found 589:593 found in patients from five additional apparently unrelated Bedouin families: a 1-bp deletion mutation in a predicted alternative splice variant of EOGT 589:740 Whole-exome sequencing followed by Sanger sequencing identified only a single mutation within this locus, shared by all affected individuals and found in patients from five additional apparently unrelated Bedouin families: a 1-bp deletion mutation in a predicted alternative splice variant of EOGT, leading to a putative truncated protein. 23860037 5 64 theme N-acetylglucosamine 924:942 arg1 transferase 944:954 EGF-domain-specific O-linked N-acetylglucosamine transferase 895:954 EGF-domain-specific O-linked N-acetylglucosamine transferase 895:954 EOGT encodes EGF-domain-specific O-linked N-acetylglucosamine transferase, responsible for extracellular O-GlcNAcylation of epidermal growth factor-like domain-containing proteins, and is essential for epithelial cell-matrix interactions. 23860037 5 64 theme N-acetylglucosamine 924:942 arg1 EOGT 882:885 EOGT 882:885 EOGT 882:885 EOGT encodes EGF-domain-specific O-linked N-acetylglucosamine transferase, responsible for extracellular O-GlcNAcylation of epidermal growth factor-like domain-containing proteins, and is essential for epithelial cell-matrix interactions. 23860037 2 65 theme LOD 427:429 arg1 individuals 414:424 affected individuals 405:424 affected individuals (LOD score 3.37) 405:441 Genome-wide linkage analysis ruled out association with known Adams-Oliver syndrome genes, identifying a single-homozygosity ∼1.8-Mb novel locus common to affected individuals (LOD score 3.37). 23860037 2 65 theme LOD 427:429 arg1 score 431:435 LOD score 3.37 427:440 LOD score 3.37 427:440 Genome-wide linkage analysis ruled out association with known Adams-Oliver syndrome genes, identifying a single-homozygosity ∼1.8-Mb novel locus common to affected individuals (LOD score 3.37). 23860037 6 66 theme intact 1180:1185 arg1 cytoskeleton 1192:1203 apparently intact cell cytoskeleton 1169:1203 apparently intact cell cytoskeleton 1169:1203 F-actin staining in diseased fibroblasts showed apparently intact cell cytoskeleton and morphology, suggesting the EOGT mutation acts not through perturbation of cytoskeleton but through other mechanisms yet to be elucidated. 23860037 3 67 theme 1-bp 669:672 arg1 mutation 683:690 a 1-bp deletion mutation 667:690 five additional apparently unrelated Bedouin families: a 1-bp deletion mutation in a predicted alternative splice variant of EOGT 612:740 Whole-exome sequencing followed by Sanger sequencing identified only a single mutation within this locus, shared by all affected individuals and found in patients from five additional apparently unrelated Bedouin families: a 1-bp deletion mutation in a predicted alternative splice variant of EOGT, leading to a putative truncated protein. 23860037 5 68 theme growth 1016:1021 arg1 proteins 1053:1060 epidermal growth factor-like domain-containing proteins 1006:1060 epidermal growth factor-like domain-containing proteins 1006:1060 EOGT encodes EGF-domain-specific O-linked N-acetylglucosamine transferase, responsible for extracellular O-GlcNAcylation of epidermal growth factor-like domain-containing proteins, and is essential for epithelial cell-matrix interactions. 28427012 2 0 theme robust 463:468 arg1 strategies 491:500 robust nonradiometric assay strategies 463:500 robust nonradiometric assay strategies 463:500 Specific inhibitors of OGT could be valuable tools to probe the biological functions of O-GlcNAcylation, but a lack of robust nonradiometric assay strategies to detect glycosylation, has impeded efforts to identify such compounds. 28427012 0 1 from biosensing 27:36 arg1 glycosylation 79:91 O-GlcNAc glycosylation 70:91 O-GlcNAc glycosylation 70:91 Label-free electrochemical biosensing of small-molecule inhibition on O-GlcNAc glycosylation. 28427012 2 2 theme Specific 344:351 arg1 inhibitors 353:362 Specific inhibitors 344:362 Specific inhibitors of OGT 344:369 Specific inhibitors of OGT could be valuable tools to probe the biological functions of O-GlcNAcylation, but a lack of robust nonradiometric assay strategies to detect glycosylation, has impeded efforts to identify such compounds. 28427012 1 3 theme promising 322:330 arg1 target 336:341 a promising new target 320:341 a promising new target 320:341 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) plays a critical role in modulating protein function in many cellular processes and human diseases such as Alzheimer's disease and type II diabetes, and has emerged as a promising new target. 28427012 1 4 theme new 332:334 arg1 target 336:341 a promising new target 320:341 a promising new target 320:341 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) plays a critical role in modulating protein function in many cellular processes and human diseases such as Alzheimer's disease and type II diabetes, and has emerged as a promising new target. 28427012 4 5 theme the 881:883 arg1 proteolysis 866:876 proteolysis 866:876 proteolysis of the glycosylated and the unglycosylated peptides by protease 866:940 There is a large difference in the abilities of proteolysis of the glycosylated and the unglycosylated peptides by protease, thus providing a sensing mechanism for OGT activity. 28427012 1 6 link O-linked 94:101 arg1 O-GlcNAc 124:131 O-GlcNAc 124:131 O-GlcNAc 124:131 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) plays a critical role in modulating protein function in many cellular processes and human diseases such as Alzheimer's disease and type II diabetes, and has emerged as a promising new target. 28427012 1 6 link O-linked 94:101 arg1 N-acetylglucosamine 103:121 O-linked N-acetylglucosamine 94:121 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) 94:150 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) plays a critical role in modulating protein function in many cellular processes and human diseases such as Alzheimer's disease and type II diabetes, and has emerged as a promising new target. 28427012 3 7 theme protease-protection 694:712 arg1 strategy 714:721 protease-protection strategy 694:721 protease-protection strategy 694:721 Here we have developed a novel label-free electrochemical biosensor for the detection of peptide O-GlcNAcylation using protease-protection strategy and electrocatalytic oxidation of tyrosine mediated by osmium bipyridine as a signal reporter. 28427012 3 7 theme protease-protection 694:712 arg1 oxidation 744:752 electrocatalytic oxidation 727:752 electrocatalytic oxidation of tyrosine mediated by osmium bipyridine 727:794 Here we have developed a novel label-free electrochemical biosensor for the detection of peptide O-GlcNAcylation using protease-protection strategy and electrocatalytic oxidation of tyrosine mediated by osmium bipyridine as a signal reporter. 28427012 3 7 theme protease-protection 694:712 arg1 reporter 808:815 a signal reporter 799:815 a signal reporter 799:815 Here we have developed a novel label-free electrochemical biosensor for the detection of peptide O-GlcNAcylation using protease-protection strategy and electrocatalytic oxidation of tyrosine mediated by osmium bipyridine as a signal reporter. 28427012 9 8 theme label-free 1547:1556 arg1 method 1574:1579 Our label-free electrochemical method 1543:1579 Our label-free electrochemical method 1543:1579 Our label-free electrochemical method is a promising candidate for protein glycosylation pathway research in screening small-molecule inhibitors of OGT. 28427012 9 8 theme label-free 1547:1556 arg1 candidate 1596:1604 a promising candidate 1584:1604 a promising candidate for protein glycosylation pathway research in screening small-molecule inhibitors of OGT 1584:1693 Our label-free electrochemical method is a promising candidate for protein glycosylation pathway research in screening small-molecule inhibitors of OGT. 28427012 4 9 theme sensing 960:966 arg1 mechanism 968:976 a sensing mechanism 958:976 a sensing mechanism for OGT activity 958:993 There is a large difference in the abilities of proteolysis of the glycosylated and the unglycosylated peptides by protease, thus providing a sensing mechanism for OGT activity. 28427012 9 10 theme electrochemical 1558:1572 arg1 method 1574:1579 Our label-free electrochemical method 1543:1579 Our label-free electrochemical method 1543:1579 Our label-free electrochemical method is a promising candidate for protein glycosylation pathway research in screening small-molecule inhibitors of OGT. 28427012 9 10 theme electrochemical 1558:1572 arg1 candidate 1596:1604 a promising candidate 1584:1604 a promising candidate for protein glycosylation pathway research in screening small-molecule inhibitors of OGT 1584:1693 Our label-free electrochemical method is a promising candidate for protein glycosylation pathway research in screening small-molecule inhibitors of OGT. 28427012 4 11 theme OGT 982:984 arg1 activity 986:993 OGT activity 982:993 OGT activity 982:993 There is a large difference in the abilities of proteolysis of the glycosylated and the unglycosylated peptides by protease, thus providing a sensing mechanism for OGT activity. 28427012 3 12 theme tyrosine 757:764 arg1 strategy 714:721 protease-protection strategy 694:721 protease-protection strategy 694:721 Here we have developed a novel label-free electrochemical biosensor for the detection of peptide O-GlcNAcylation using protease-protection strategy and electrocatalytic oxidation of tyrosine mediated by osmium bipyridine as a signal reporter. 28427012 3 12 theme tyrosine 757:764 arg1 oxidation 744:752 electrocatalytic oxidation 727:752 electrocatalytic oxidation of tyrosine mediated by osmium bipyridine 727:794 Here we have developed a novel label-free electrochemical biosensor for the detection of peptide O-GlcNAcylation using protease-protection strategy and electrocatalytic oxidation of tyrosine mediated by osmium bipyridine as a signal reporter. 28427012 3 12 theme tyrosine 757:764 arg1 reporter 808:815 a signal reporter 799:815 a signal reporter 799:815 Here we have developed a novel label-free electrochemical biosensor for the detection of peptide O-GlcNAcylation using protease-protection strategy and electrocatalytic oxidation of tyrosine mediated by osmium bipyridine as a signal reporter. 28427012 6 13 theme unglycosylated 1257:1270 arg1 peptides 1272:1279 the unglycosylated peptides 1253:1279 the unglycosylated peptides 1253:1279 However, when the O-GlcNAcylation is successfully inhibited using a small molecule, the unglycosylated peptides can be cleaved easily and lead to low current signal. 28427012 1 14 theme O-linked 94:101 arg1 O-GlcNAc 124:131 O-GlcNAc 124:131 O-GlcNAc 124:131 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) plays a critical role in modulating protein function in many cellular processes and human diseases such as Alzheimer's disease and type II diabetes, and has emerged as a promising new target. 28427012 1 14 theme O-linked 94:101 arg1 N-acetylglucosamine 103:121 O-linked N-acetylglucosamine 94:121 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) 94:150 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) plays a critical role in modulating protein function in many cellular processes and human diseases such as Alzheimer's disease and type II diabetes, and has emerged as a promising new target. 28427012 2 15 contain has 527:529 arg2 efforts 539:545 efforts 539:545 efforts 539:545 Specific inhibitors of OGT could be valuable tools to probe the biological functions of O-GlcNAcylation, but a lack of robust nonradiometric assay strategies to detect glycosylation, has impeded efforts to identify such compounds. 28427012 2 15 contain has 527:529 arg1 lack 455:458 a lack 453:458 a lack 453:458 Specific inhibitors of OGT could be valuable tools to probe the biological functions of O-GlcNAcylation, but a lack of robust nonradiometric assay strategies to detect glycosylation, has impeded efforts to identify such compounds. 28427012 2 16 theme valuable 380:387 arg1 tools 389:393 valuable tools 380:393 valuable tools 380:393 Specific inhibitors of OGT could be valuable tools to probe the biological functions of O-GlcNAcylation, but a lack of robust nonradiometric assay strategies to detect glycosylation, has impeded efforts to identify such compounds. 28427012 2 17 theme strategies 491:500 arg1 lack 455:458 a lack 453:458 a lack 453:458 Specific inhibitors of OGT could be valuable tools to probe the biological functions of O-GlcNAcylation, but a lack of robust nonradiometric assay strategies to detect glycosylation, has impeded efforts to identify such compounds. 28427012 3 18 theme electrocatalytic 727:742 arg1 strategy 714:721 protease-protection strategy 694:721 protease-protection strategy 694:721 Here we have developed a novel label-free electrochemical biosensor for the detection of peptide O-GlcNAcylation using protease-protection strategy and electrocatalytic oxidation of tyrosine mediated by osmium bipyridine as a signal reporter. 28427012 3 18 theme electrocatalytic 727:742 arg1 oxidation 744:752 electrocatalytic oxidation 727:752 electrocatalytic oxidation of tyrosine mediated by osmium bipyridine 727:794 Here we have developed a novel label-free electrochemical biosensor for the detection of peptide O-GlcNAcylation using protease-protection strategy and electrocatalytic oxidation of tyrosine mediated by osmium bipyridine as a signal reporter. 28427012 3 18 theme electrocatalytic 727:742 arg1 reporter 808:815 a signal reporter 799:815 a signal reporter 799:815 Here we have developed a novel label-free electrochemical biosensor for the detection of peptide O-GlcNAcylation using protease-protection strategy and electrocatalytic oxidation of tyrosine mediated by osmium bipyridine as a signal reporter. 28427012 9 19 theme screening 1652:1660 arg1 inhibitors 1677:1686 screening small-molecule inhibitors 1652:1686 screening small-molecule inhibitors of OGT 1652:1693 Our label-free electrochemical method is a promising candidate for protein glycosylation pathway research in screening small-molecule inhibitors of OGT. 28427012 1 20 theme N-acetylglucosamine 103:121 arg1 OGT 147:149 OGT 147:149 OGT 147:149 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) plays a critical role in modulating protein function in many cellular processes and human diseases such as Alzheimer's disease and type II diabetes, and has emerged as a promising new target. 28427012 1 20 theme N-acetylglucosamine 103:121 arg1 transferase 134:144 O-linked N-acetylglucosamine (O-GlcNAc) transferase 94:144 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) 94:150 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) plays a critical role in modulating protein function in many cellular processes and human diseases such as Alzheimer's disease and type II diabetes, and has emerged as a promising new target. 28427012 5 21 theme high 1110:1113 arg1 response 1123:1130 a high current response 1108:1130 a high current response on indium tin oxide (ITO) electrode 1108:1166 When the O-GlcNAcylation is achieved, the glycosylated peptides cannot be cleaved by proteinase K and result in a high current response on indium tin oxide (ITO) electrode. 28427012 1 22 theme protein 188:194 arg1 function 196:203 protein function 188:203 protein function in many cellular processes and human diseases such as Alzheimer's disease and type II diabetes 188:298 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) plays a critical role in modulating protein function in many cellular processes and human diseases such as Alzheimer's disease and type II diabetes, and has emerged as a promising new target. 28427012 0 23 theme electrochemical 11:25 arg1 biosensing 27:36 Label-free electrochemical biosensing 0:36 Label-free electrochemical biosensing of small-molecule inhibition on O-GlcNAc glycosylation. 0:92 Label-free electrochemical biosensing of small-molecule inhibition on O-GlcNAc glycosylation. 28427012 9 24 theme OGT 1691:1693 arg1 inhibitors 1677:1686 screening small-molecule inhibitors 1652:1686 screening small-molecule inhibitors of OGT 1652:1693 Our label-free electrochemical method is a promising candidate for protein glycosylation pathway research in screening small-molecule inhibitors of OGT. 28427012 3 25 theme osmium 778:783 arg1 bipyridine 785:794 osmium bipyridine 778:794 osmium bipyridine 778:794 Here we have developed a novel label-free electrochemical biosensor for the detection of peptide O-GlcNAcylation using protease-protection strategy and electrocatalytic oxidation of tyrosine mediated by osmium bipyridine as a signal reporter. 28427012 7 26 theme well-defined 1403:1414 arg1 inhibitor 1435:1443 a well-defined small-molecule OGT inhibitor 1401:1443 a well-defined small-molecule OGT inhibitor 1401:1443 Peptide O-GlcNAcylation reaction was performed in the presence of a well-defined small-molecule OGT inhibitor. 28427012 4 27 theme unglycosylated 906:919 arg1 peptides 921:928 the unglycosylated peptides 902:928 the unglycosylated peptides 902:928 There is a large difference in the abilities of proteolysis of the glycosylated and the unglycosylated peptides by protease, thus providing a sensing mechanism for OGT activity. 28427012 0 28 theme Label-free 0:9 arg1 biosensing 27:36 Label-free electrochemical biosensing 0:36 Label-free electrochemical biosensing of small-molecule inhibition on O-GlcNAc glycosylation. 0:92 Label-free electrochemical biosensing of small-molecule inhibition on O-GlcNAc glycosylation. 28427012 1 29 theme type 283:286 arg1 diabetes 291:298 type II diabetes 283:298 type II diabetes 283:298 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) plays a critical role in modulating protein function in many cellular processes and human diseases such as Alzheimer's disease and type II diabetes, and has emerged as a promising new target. 28427012 4 30 theme proteolysis 866:876 arg1 abilities 853:861 the abilities 849:861 the abilities of proteolysis of the glycosylated and the unglycosylated peptides by protease 849:940 There is a large difference in the abilities of proteolysis of the glycosylated and the unglycosylated peptides by protease, thus providing a sensing mechanism for OGT activity. 28427012 7 31 theme small-molecule 1416:1429 arg1 inhibitor 1435:1443 a well-defined small-molecule OGT inhibitor 1401:1443 a well-defined small-molecule OGT inhibitor 1401:1443 Peptide O-GlcNAcylation reaction was performed in the presence of a well-defined small-molecule OGT inhibitor. 28427012 2 32 theme OGT 367:369 arg1 inhibitors 353:362 Specific inhibitors 344:362 Specific inhibitors of OGT 344:369 Specific inhibitors of OGT could be valuable tools to probe the biological functions of O-GlcNAcylation, but a lack of robust nonradiometric assay strategies to detect glycosylation, has impeded efforts to identify such compounds. 28427012 7 33 theme Peptide 1335:1341 arg1 reaction 1359:1366 Peptide O-GlcNAcylation reaction 1335:1366 Peptide O-GlcNAcylation reaction 1335:1366 Peptide O-GlcNAcylation reaction was performed in the presence of a well-defined small-molecule OGT inhibitor. 28427012 9 34 theme protein 1610:1616 arg1 research 1640:1647 protein glycosylation pathway research 1610:1647 protein glycosylation pathway research in screening small-molecule inhibitors of OGT 1610:1693 Our label-free electrochemical method is a promising candidate for protein glycosylation pathway research in screening small-molecule inhibitors of OGT. 28427012 1 35 theme many 208:211 arg1 diabetes 291:298 type II diabetes 283:298 type II diabetes 283:298 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) plays a critical role in modulating protein function in many cellular processes and human diseases such as Alzheimer's disease and type II diabetes, and has emerged as a promising new target. 28427012 1 35 theme many 208:211 arg1 disease 271:277 Alzheimer's disease 259:277 Alzheimer's disease 259:277 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) plays a critical role in modulating protein function in many cellular processes and human diseases such as Alzheimer's disease and type II diabetes, and has emerged as a promising new target. 28427012 1 35 theme many 208:211 arg1 processes 222:230 many cellular processes 208:230 many cellular processes 208:230 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) plays a critical role in modulating protein function in many cellular processes and human diseases such as Alzheimer's disease and type II diabetes, and has emerged as a promising new target. 28427012 2 36 theme biological 408:417 arg1 functions 419:427 the biological functions 404:427 the biological functions of O-GlcNAcylation 404:446 Specific inhibitors of OGT could be valuable tools to probe the biological functions of O-GlcNAcylation, but a lack of robust nonradiometric assay strategies to detect glycosylation, has impeded efforts to identify such compounds. 28427012 5 37 theme indium 1135:1140 arg1 ITO 1153:1155 ITO 1153:1155 ITO 1153:1155 When the O-GlcNAcylation is achieved, the glycosylated peptides cannot be cleaved by proteinase K and result in a high current response on indium tin oxide (ITO) electrode. 28427012 5 37 theme indium 1135:1140 arg1 oxide 1146:1150 indium tin oxide 1135:1150 indium tin oxide (ITO) electrode 1135:1166 When the O-GlcNAcylation is achieved, the glycosylated peptides cannot be cleaved by proteinase K and result in a high current response on indium tin oxide (ITO) electrode. 28427012 7 38 theme OGT 1431:1433 arg1 inhibitor 1435:1443 a well-defined small-molecule OGT inhibitor 1401:1443 a well-defined small-molecule OGT inhibitor 1401:1443 Peptide O-GlcNAcylation reaction was performed in the presence of a well-defined small-molecule OGT inhibitor. 28427012 9 39 theme promising 1586:1594 arg1 method 1574:1579 Our label-free electrochemical method 1543:1579 Our label-free electrochemical method 1543:1579 Our label-free electrochemical method is a promising candidate for protein glycosylation pathway research in screening small-molecule inhibitors of OGT. 28427012 9 39 theme promising 1586:1594 arg1 candidate 1596:1604 a promising candidate 1584:1604 a promising candidate for protein glycosylation pathway research in screening small-molecule inhibitors of OGT 1584:1693 Our label-free electrochemical method is a promising candidate for protein glycosylation pathway research in screening small-molecule inhibitors of OGT. 28427012 1 40 theme cellular 213:220 arg1 diabetes 291:298 type II diabetes 283:298 type II diabetes 283:298 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) plays a critical role in modulating protein function in many cellular processes and human diseases such as Alzheimer's disease and type II diabetes, and has emerged as a promising new target. 28427012 1 40 theme cellular 213:220 arg1 disease 271:277 Alzheimer's disease 259:277 Alzheimer's disease 259:277 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) plays a critical role in modulating protein function in many cellular processes and human diseases such as Alzheimer's disease and type II diabetes, and has emerged as a promising new target. 28427012 1 40 theme cellular 213:220 arg1 processes 222:230 many cellular processes 208:230 many cellular processes 208:230 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) plays a critical role in modulating protein function in many cellular processes and human diseases such as Alzheimer's disease and type II diabetes, and has emerged as a promising new target. 28427012 0 41 theme inhibition 56:65 arg1 biosensing 27:36 Label-free electrochemical biosensing 0:36 Label-free electrochemical biosensing of small-molecule inhibition on O-GlcNAc glycosylation. 0:92 Label-free electrochemical biosensing of small-molecule inhibition on O-GlcNAc glycosylation. 28427012 9 42 theme glycosylation 1618:1630 arg1 research 1640:1647 protein glycosylation pathway research 1610:1647 protein glycosylation pathway research in screening small-molecule inhibitors of OGT 1610:1693 Our label-free electrochemical method is a promising candidate for protein glycosylation pathway research in screening small-molecule inhibitors of OGT. 28427012 6 43 theme current 1319:1325 arg1 signal 1327:1332 low current signal 1315:1332 low current signal 1315:1332 However, when the O-GlcNAcylation is successfully inhibited using a small molecule, the unglycosylated peptides can be cleaved easily and lead to low current signal. 28427012 5 44 gly glycosylated 1038:1049 arg1 peptides 1051:1058 the glycosylated peptides 1034:1058 the glycosylated peptides 1034:1058 When the O-GlcNAcylation is achieved, the glycosylated peptides cannot be cleaved by proteinase K and result in a high current response on indium tin oxide (ITO) electrode. 28427012 6 45 theme small 1237:1241 arg1 molecule 1243:1250 a small molecule 1235:1250 a small molecule 1235:1250 However, when the O-GlcNAcylation is successfully inhibited using a small molecule, the unglycosylated peptides can be cleaved easily and lead to low current signal. 28427012 0 46 theme small-molecule 41:54 arg1 inhibition 56:65 small-molecule inhibition 41:65 small-molecule inhibition 41:65 Label-free electrochemical biosensing of small-molecule inhibition on O-GlcNAc glycosylation. 28427012 3 47 theme signal 801:806 arg1 strategy 714:721 protease-protection strategy 694:721 protease-protection strategy 694:721 Here we have developed a novel label-free electrochemical biosensor for the detection of peptide O-GlcNAcylation using protease-protection strategy and electrocatalytic oxidation of tyrosine mediated by osmium bipyridine as a signal reporter. 28427012 3 47 theme signal 801:806 arg1 oxidation 744:752 electrocatalytic oxidation 727:752 electrocatalytic oxidation of tyrosine mediated by osmium bipyridine 727:794 Here we have developed a novel label-free electrochemical biosensor for the detection of peptide O-GlcNAcylation using protease-protection strategy and electrocatalytic oxidation of tyrosine mediated by osmium bipyridine as a signal reporter. 28427012 3 47 theme signal 801:806 arg1 reporter 808:815 a signal reporter 799:815 a signal reporter 799:815 Here we have developed a novel label-free electrochemical biosensor for the detection of peptide O-GlcNAcylation using protease-protection strategy and electrocatalytic oxidation of tyrosine mediated by osmium bipyridine as a signal reporter. 28427012 6 48 theme low 1315:1317 arg1 signal 1327:1332 low current signal 1315:1332 low current signal 1315:1332 However, when the O-GlcNAcylation is successfully inhibited using a small molecule, the unglycosylated peptides can be cleaved easily and lead to low current signal. 28427012 3 49 theme electrochemical 617:631 arg1 biosensor 633:641 a novel label-free electrochemical biosensor 598:641 a novel label-free electrochemical biosensor for the detection of peptide O-GlcNAcylation 598:686 Here we have developed a novel label-free electrochemical biosensor for the detection of peptide O-GlcNAcylation using protease-protection strategy and electrocatalytic oxidation of tyrosine mediated by osmium bipyridine as a signal reporter. 28427012 4 50 theme large 829:833 arg1 difference 835:844 a large difference 827:844 a large difference in the abilities of proteolysis of the glycosylated and the unglycosylated peptides by protease 827:940 There is a large difference in the abilities of proteolysis of the glycosylated and the unglycosylated peptides by protease, thus providing a sensing mechanism for OGT activity. 28427012 0 51 theme O-GlcNAc 70:77 arg1 glycosylation 79:91 O-GlcNAc glycosylation 70:91 O-GlcNAc glycosylation 70:91 Label-free electrochemical biosensing of small-molecule inhibition on O-GlcNAc glycosylation. 28427012 8 52 used used 1496:1499 arg2 biosensor 1477:1485 the biosensor 1473:1485 the biosensor 1473:1485 The results indicated that the biosensor could be used to screen the OGT inhibitors effectively. 28427012 4 53 theme peptides 921:928 arg1 proteolysis 866:876 proteolysis 866:876 proteolysis of the glycosylated and the unglycosylated peptides by protease 866:940 There is a large difference in the abilities of proteolysis of the glycosylated and the unglycosylated peptides by protease, thus providing a sensing mechanism for OGT activity. 28427012 2 54 theme nonradiometric 470:483 arg1 strategies 491:500 robust nonradiometric assay strategies 463:500 robust nonradiometric assay strategies 463:500 Specific inhibitors of OGT could be valuable tools to probe the biological functions of O-GlcNAcylation, but a lack of robust nonradiometric assay strategies to detect glycosylation, has impeded efforts to identify such compounds. 28427012 9 55 theme pathway 1632:1638 arg1 research 1640:1647 protein glycosylation pathway research 1610:1647 protein glycosylation pathway research in screening small-molecule inhibitors of OGT 1610:1693 Our label-free electrochemical method is a promising candidate for protein glycosylation pathway research in screening small-molecule inhibitors of OGT. 28427012 5 56 theme current 1115:1121 arg1 response 1123:1130 a high current response 1108:1130 a high current response on indium tin oxide (ITO) electrode 1108:1166 When the O-GlcNAcylation is achieved, the glycosylated peptides cannot be cleaved by proteinase K and result in a high current response on indium tin oxide (ITO) electrode. 28427012 5 57 theme tin 1142:1144 arg1 ITO 1153:1155 ITO 1153:1155 ITO 1153:1155 When the O-GlcNAcylation is achieved, the glycosylated peptides cannot be cleaved by proteinase K and result in a high current response on indium tin oxide (ITO) electrode. 28427012 5 57 theme tin 1142:1144 arg1 oxide 1146:1150 indium tin oxide 1135:1150 indium tin oxide (ITO) electrode 1135:1166 When the O-GlcNAcylation is achieved, the glycosylated peptides cannot be cleaved by proteinase K and result in a high current response on indium tin oxide (ITO) electrode. 28427012 5 58 theme oxide 1146:1150 arg1 electrode 1158:1166 indium tin oxide (ITO) electrode 1135:1166 indium tin oxide (ITO) electrode 1135:1166 When the O-GlcNAcylation is achieved, the glycosylated peptides cannot be cleaved by proteinase K and result in a high current response on indium tin oxide (ITO) electrode. 28427012 2 59 theme such 559:562 arg1 compounds 564:572 such compounds 559:572 such compounds 559:572 Specific inhibitors of OGT could be valuable tools to probe the biological functions of O-GlcNAcylation, but a lack of robust nonradiometric assay strategies to detect glycosylation, has impeded efforts to identify such compounds. 28427012 3 60 theme peptide 664:670 arg1 O-GlcNAcylation 672:686 peptide O-GlcNAcylation 664:686 peptide O-GlcNAcylation 664:686 Here we have developed a novel label-free electrochemical biosensor for the detection of peptide O-GlcNAcylation using protease-protection strategy and electrocatalytic oxidation of tyrosine mediated by osmium bipyridine as a signal reporter. 28427012 9 61 theme small-molecule 1662:1675 arg1 inhibitors 1677:1686 screening small-molecule inhibitors 1652:1686 screening small-molecule inhibitors of OGT 1652:1693 Our label-free electrochemical method is a promising candidate for protein glycosylation pathway research in screening small-molecule inhibitors of OGT. 28427012 4 62 from difference 835:844 arg1 abilities 853:861 the abilities 849:861 the abilities of proteolysis of the glycosylated and the unglycosylated peptides by protease 849:940 There is a large difference in the abilities of proteolysis of the glycosylated and the unglycosylated peptides by protease, thus providing a sensing mechanism for OGT activity. 28427012 6 63 gly unglycosylated 1257:1270 arg1 peptides 1272:1279 the unglycosylated peptides 1253:1279 the unglycosylated peptides 1253:1279 However, when the O-GlcNAcylation is successfully inhibited using a small molecule, the unglycosylated peptides can be cleaved easily and lead to low current signal. 28427012 3 64 theme O-GlcNAcylation 672:686 arg1 detection 651:659 the detection 647:659 the detection of peptide O-GlcNAcylation 647:686 Here we have developed a novel label-free electrochemical biosensor for the detection of peptide O-GlcNAcylation using protease-protection strategy and electrocatalytic oxidation of tyrosine mediated by osmium bipyridine as a signal reporter. 28427012 3 65 theme novel 600:604 arg1 biosensor 633:641 a novel label-free electrochemical biosensor 598:641 a novel label-free electrochemical biosensor for the detection of peptide O-GlcNAcylation 598:686 Here we have developed a novel label-free electrochemical biosensor for the detection of peptide O-GlcNAcylation using protease-protection strategy and electrocatalytic oxidation of tyrosine mediated by osmium bipyridine as a signal reporter. 28427012 5 66 theme glycosylated 1038:1049 arg1 peptides 1051:1058 the glycosylated peptides 1034:1058 the glycosylated peptides 1034:1058 When the O-GlcNAcylation is achieved, the glycosylated peptides cannot be cleaved by proteinase K and result in a high current response on indium tin oxide (ITO) electrode. 28427012 1 67 theme human 236:240 arg1 diabetes 291:298 type II diabetes 283:298 type II diabetes 283:298 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) plays a critical role in modulating protein function in many cellular processes and human diseases such as Alzheimer's disease and type II diabetes, and has emerged as a promising new target. 28427012 1 67 theme human 236:240 arg1 disease 271:277 Alzheimer's disease 259:277 Alzheimer's disease 259:277 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) plays a critical role in modulating protein function in many cellular processes and human diseases such as Alzheimer's disease and type II diabetes, and has emerged as a promising new target. 28427012 1 67 theme human 236:240 arg1 diseases 242:249 human diseases 236:249 human diseases such as Alzheimer's disease and type II diabetes 236:298 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) plays a critical role in modulating protein function in many cellular processes and human diseases such as Alzheimer's disease and type II diabetes, and has emerged as a promising new target. 28427012 7 68 theme inhibitor 1435:1443 arg1 presence 1389:1396 the presence 1385:1396 the presence of a well-defined small-molecule OGT inhibitor 1385:1443 Peptide O-GlcNAcylation reaction was performed in the presence of a well-defined small-molecule OGT inhibitor. 28427012 3 69 theme label-free 606:615 arg1 biosensor 633:641 a novel label-free electrochemical biosensor 598:641 a novel label-free electrochemical biosensor for the detection of peptide O-GlcNAcylation 598:686 Here we have developed a novel label-free electrochemical biosensor for the detection of peptide O-GlcNAcylation using protease-protection strategy and electrocatalytic oxidation of tyrosine mediated by osmium bipyridine as a signal reporter. 28427012 1 70 from function 196:203 arg1 diabetes 291:298 type II diabetes 283:298 type II diabetes 283:298 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) plays a critical role in modulating protein function in many cellular processes and human diseases such as Alzheimer's disease and type II diabetes, and has emerged as a promising new target. 28427012 1 70 from function 196:203 arg1 disease 271:277 Alzheimer's disease 259:277 Alzheimer's disease 259:277 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) plays a critical role in modulating protein function in many cellular processes and human diseases such as Alzheimer's disease and type II diabetes, and has emerged as a promising new target. 28427012 1 70 from function 196:203 arg1 processes 222:230 many cellular processes 208:230 many cellular processes 208:230 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) plays a critical role in modulating protein function in many cellular processes and human diseases such as Alzheimer's disease and type II diabetes, and has emerged as a promising new target. 28427012 1 70 from function 196:203 arg1 diseases 242:249 human diseases 236:249 human diseases such as Alzheimer's disease and type II diabetes 236:298 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) plays a critical role in modulating protein function in many cellular processes and human diseases such as Alzheimer's disease and type II diabetes, and has emerged as a promising new target. 28427012 9 71 from research 1640:1647 arg1 inhibitors 1677:1686 screening small-molecule inhibitors 1652:1686 screening small-molecule inhibitors of OGT 1652:1693 Our label-free electrochemical method is a promising candidate for protein glycosylation pathway research in screening small-molecule inhibitors of OGT. 28427012 2 72 theme assay 485:489 arg1 strategies 491:500 robust nonradiometric assay strategies 463:500 robust nonradiometric assay strategies 463:500 Specific inhibitors of OGT could be valuable tools to probe the biological functions of O-GlcNAcylation, but a lack of robust nonradiometric assay strategies to detect glycosylation, has impeded efforts to identify such compounds. 28427012 5 73 theme proteinase 1081:1090 arg1 K 1092:1092 proteinase K 1081:1092 proteinase K 1081:1092 When the O-GlcNAcylation is achieved, the glycosylated peptides cannot be cleaved by proteinase K and result in a high current response on indium tin oxide (ITO) electrode. 28427012 5 74 from response 1123:1130 arg1 electrode 1158:1166 indium tin oxide (ITO) electrode 1135:1166 indium tin oxide (ITO) electrode 1135:1166 When the O-GlcNAcylation is achieved, the glycosylated peptides cannot be cleaved by proteinase K and result in a high current response on indium tin oxide (ITO) electrode. 28427012 4 75 gly unglycosylated 906:919 arg1 peptides 921:928 the unglycosylated peptides 902:928 the unglycosylated peptides 902:928 There is a large difference in the abilities of proteolysis of the glycosylated and the unglycosylated peptides by protease, thus providing a sensing mechanism for OGT activity. 28427012 2 76 theme O-GlcNAcylation 432:446 arg1 functions 419:427 the biological functions 404:427 the biological functions of O-GlcNAcylation 404:446 Specific inhibitors of OGT could be valuable tools to probe the biological functions of O-GlcNAcylation, but a lack of robust nonradiometric assay strategies to detect glycosylation, has impeded efforts to identify such compounds. 28427012 7 77 theme O-GlcNAcylation 1343:1357 arg1 reaction 1359:1366 Peptide O-GlcNAcylation reaction 1335:1366 Peptide O-GlcNAcylation reaction 1335:1366 Peptide O-GlcNAcylation reaction was performed in the presence of a well-defined small-molecule OGT inhibitor. 28427012 1 78 theme critical 160:167 arg1 role 169:172 a critical role 158:172 a critical role 158:172 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) plays a critical role in modulating protein function in many cellular processes and human diseases such as Alzheimer's disease and type II diabetes, and has emerged as a promising new target. 28427012 8 79 theme OGT 1515:1517 arg1 inhibitors 1519:1528 the OGT inhibitors 1511:1528 the OGT inhibitors 1511:1528 The results indicated that the biosensor could be used to screen the OGT inhibitors effectively. 28416608 8 0 theme activating 1217:1226 arg1 acetylation 1228:1238 CREB-binding protein (CBP)/p300-dependent activating acetylation 1175:1238 CREB-binding protein (CBP)/p300-dependent activating acetylation of p65 1175:1245 O-GlcNAcylation of p65 at Thr-305 and Ser-319 increased CREB-binding protein (CBP)/p300-dependent activating acetylation of p65 at Lys-310, contributing to NF-κB transcriptional activation. 28416608 9 1 theme p65 1478:1480 arg1 phosphorylation 1459:1473 IKK-mediated activating phosphorylation 1435:1473 IKK-mediated activating phosphorylation of p65 at Ser-536, contributing to NF-κB activation 1435:1525 Moreover, elevation of O-GlcNAcylation by overexpression of OGT increased the expression of p300, IKKα, and IKKβ and promoted IKK-mediated activating phosphorylation of p65 at Ser-536, contributing to NF-κB activation. 28416608 2 2 theme critical 403:410 arg1 roles 412:416 critical roles 403:416 critical roles 403:416 O-GlcNAcylation, analogous to phosphorylation, plays critical roles in gene expression through direct modification of transcription factors, such as NF-κB. 28416608 8 3 theme CREB-binding 1175:1186 arg1 CBP 1197:1199 CBP 1197:1199 CBP 1197:1199 O-GlcNAcylation of p65 at Thr-305 and Ser-319 increased CREB-binding protein (CBP)/p300-dependent activating acetylation of p65 at Lys-310, contributing to NF-κB transcriptional activation. 28416608 8 3 theme CREB-binding 1175:1186 arg1 protein 1188:1194 CREB-binding protein 1175:1194 CREB-binding protein (CBP)/p300-dependent activating acetylation of p65 1175:1245 O-GlcNAcylation of p65 at Thr-305 and Ser-319 increased CREB-binding protein (CBP)/p300-dependent activating acetylation of p65 at Lys-310, contributing to NF-κB transcriptional activation. 28416608 8 4 theme /p300-dependent 1201:1215 arg1 acetylation 1228:1238 CREB-binding protein (CBP)/p300-dependent activating acetylation 1175:1238 CREB-binding protein (CBP)/p300-dependent activating acetylation of p65 1175:1245 O-GlcNAcylation of p65 at Thr-305 and Ser-319 increased CREB-binding protein (CBP)/p300-dependent activating acetylation of p65 at Lys-310, contributing to NF-κB transcriptional activation. 28416608 8 5 theme p65 1243:1245 arg1 acetylation 1228:1238 CREB-binding protein (CBP)/p300-dependent activating acetylation 1175:1238 CREB-binding protein (CBP)/p300-dependent activating acetylation of p65 1175:1245 O-GlcNAcylation of p65 at Thr-305 and Ser-319 increased CREB-binding protein (CBP)/p300-dependent activating acetylation of p65 at Lys-310, contributing to NF-κB transcriptional activation. 28416608 1 6 theme covalent 188:195 arg1 addition 197:204 the covalent addition 184:204 the covalent addition of an O-linked β-N-acetylglucosamine (O-GlcNAc) sugar moiety to hydroxyl groups of serine/threonine residues of cytosolic and nuclear proteins 184:347 O-GlcNAcylation is the covalent addition of an O-linked β-N-acetylglucosamine (O-GlcNAc) sugar moiety to hydroxyl groups of serine/threonine residues of cytosolic and nuclear proteins. 28416608 1 6 theme covalent 188:195 arg1 O-GlcNAcylation 165:179 O-GlcNAcylation 165:179 O-GlcNAcylation 165:179 O-GlcNAcylation is the covalent addition of an O-linked β-N-acetylglucosamine (O-GlcNAc) sugar moiety to hydroxyl groups of serine/threonine residues of cytosolic and nuclear proteins. 28416608 10 7 theme p65 1637:1639 arg1 O-GlcNAcylation 1618:1632 the O-GlcNAcylation 1614:1632 the O-GlcNAcylation of p65 at Thr-305 1614:1650 In addition, we also identified phosphorylation of p65 at Thr-308, which might impair the O-GlcNAcylation of p65 at Thr-305. 28416608 11 8 theme oncogenic 1727:1735 arg1 O-GlcNAcylation 1737:1751 both non-pathological and oncogenic O-GlcNAcylation 1701:1751 both non-pathological and oncogenic O-GlcNAcylation 1701:1751 These results indicate mechanisms through which both non-pathological and oncogenic O-GlcNAcylation regulate NF-κB signaling through interplay with phosphorylation and acetylation. 28416608 1 9 theme serine/threonine 289:304 arg1 proteins 340:347 cytosolic and nuclear proteins 318:347 cytosolic and nuclear proteins 318:347 O-GlcNAcylation is the covalent addition of an O-linked β-N-acetylglucosamine (O-GlcNAc) sugar moiety to hydroxyl groups of serine/threonine residues of cytosolic and nuclear proteins. 28416608 1 9 theme serine/threonine 289:304 arg1 residues 306:313 serine/threonine residues 289:313 serine/threonine residues of cytosolic and nuclear proteins 289:347 O-GlcNAcylation is the covalent addition of an O-linked β-N-acetylglucosamine (O-GlcNAc) sugar moiety to hydroxyl groups of serine/threonine residues of cytosolic and nuclear proteins. 28416608 1 10 theme residues 306:313 arg1 proteins 340:347 cytosolic and nuclear proteins 318:347 cytosolic and nuclear proteins 318:347 O-GlcNAcylation is the covalent addition of an O-linked β-N-acetylglucosamine (O-GlcNAc) sugar moiety to hydroxyl groups of serine/threonine residues of cytosolic and nuclear proteins. 28416608 1 10 theme residues 306:313 arg1 groups 279:284 hydroxyl groups 270:284 hydroxyl groups of serine/threonine residues of cytosolic and nuclear proteins 270:347 O-GlcNAcylation is the covalent addition of an O-linked β-N-acetylglucosamine (O-GlcNAc) sugar moiety to hydroxyl groups of serine/threonine residues of cytosolic and nuclear proteins. 28416608 1 10 theme residues 306:313 arg1 residues 306:313 serine/threonine residues 289:313 serine/threonine residues of cytosolic and nuclear proteins 289:347 O-GlcNAcylation is the covalent addition of an O-linked β-N-acetylglucosamine (O-GlcNAc) sugar moiety to hydroxyl groups of serine/threonine residues of cytosolic and nuclear proteins. 28416608 9 11 theme p300 1401:1404 arg1 expression 1387:1396 the expression 1383:1396 the expression of p300, IKKα, and IKKβ 1383:1420 Moreover, elevation of O-GlcNAcylation by overexpression of OGT increased the expression of p300, IKKα, and IKKβ and promoted IKK-mediated activating phosphorylation of p65 at Ser-536, contributing to NF-κB activation. 28416608 3 12 theme NF-κB 527:531 arg1 O-GlcNAcylation 533:547 Aberrantly increased NF-κB O-GlcNAcylation 506:547 Aberrantly increased NF-κB O-GlcNAcylation 506:547 Aberrantly increased NF-κB O-GlcNAcylation has been linked to NF-κB constitutive activation and cancer development. 28416608 9 13 theme NF-κB 1510:1514 arg1 activation 1516:1525 NF-κB activation 1510:1525 NF-κB activation 1510:1525 Moreover, elevation of O-GlcNAcylation by overexpression of OGT increased the expression of p300, IKKα, and IKKβ and promoted IKK-mediated activating phosphorylation of p65 at Ser-536, contributing to NF-κB activation. 28416608 2 14 theme direct 445:450 arg1 modification 452:463 direct modification 445:463 direct modification of transcription factors, such as NF-κB 445:503 O-GlcNAcylation, analogous to phosphorylation, plays critical roles in gene expression through direct modification of transcription factors, such as NF-κB. 28416608 3 15 theme increased 517:525 arg1 O-GlcNAcylation 533:547 Aberrantly increased NF-κB O-GlcNAcylation 506:547 Aberrantly increased NF-κB O-GlcNAcylation 506:547 Aberrantly increased NF-κB O-GlcNAcylation has been linked to NF-κB constitutive activation and cancer development. 28416608 8 16 from Ser-319 1157:1163 arg1 O-GlcNAcylation 1119:1133 O-GlcNAcylation 1119:1133 O-GlcNAcylation of p65 at Thr-305 and Ser-319 1119:1163 O-GlcNAcylation of p65 at Thr-305 and Ser-319 increased CREB-binding protein (CBP)/p300-dependent activating acetylation of p65 at Lys-310, contributing to NF-κB transcriptional activation. 28416608 1 17 link O-linked 212:219 arg1 moiety 260:265 an O-linked β-N-acetylglucosamine (O-GlcNAc) sugar moiety 209:265 an O-linked β-N-acetylglucosamine (O-GlcNAc) sugar moiety 209:265 O-GlcNAcylation is the covalent addition of an O-linked β-N-acetylglucosamine (O-GlcNAc) sugar moiety to hydroxyl groups of serine/threonine residues of cytosolic and nuclear proteins. 28416608 3 18 theme cancer 602:607 arg1 development 609:619 cancer development 602:619 cancer development 602:619 Aberrantly increased NF-κB O-GlcNAcylation has been linked to NF-κB constitutive activation and cancer development. 28416608 9 19 theme IKKα 1407:1410 arg1 expression 1387:1396 the expression 1383:1396 the expression of p300, IKKα, and IKKβ 1383:1420 Moreover, elevation of O-GlcNAcylation by overexpression of OGT increased the expression of p300, IKKα, and IKKβ and promoted IKK-mediated activating phosphorylation of p65 at Ser-536, contributing to NF-κB activation. 28416608 8 20 theme p65 1138:1140 arg1 O-GlcNAcylation 1119:1133 O-GlcNAcylation 1119:1133 O-GlcNAcylation of p65 at Thr-305 and Ser-319 1119:1163 O-GlcNAcylation of p65 at Thr-305 and Ser-319 increased CREB-binding protein (CBP)/p300-dependent activating acetylation of p65 at Lys-310, contributing to NF-κB transcriptional activation. 28416608 0 21 with interplay 117:125 arg1 acetylation 152:162 acetylation 152:162 acetylation 152:162 Hyper-O-GlcNAcylation activates nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) signaling through interplay with phosphorylation and acetylation. 28416608 0 21 with interplay 117:125 arg1 phosphorylation 132:146 phosphorylation 132:146 phosphorylation 132:146 Hyper-O-GlcNAcylation activates nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) signaling through interplay with phosphorylation and acetylation. 28416608 8 22 theme transcriptional 1281:1295 arg1 activation 1297:1306 NF-κB transcriptional activation 1275:1306 NF-κB transcriptional activation 1275:1306 O-GlcNAcylation of p65 at Thr-305 and Ser-319 increased CREB-binding protein (CBP)/p300-dependent activating acetylation of p65 at Lys-310, contributing to NF-κB transcriptional activation. 28416608 9 23 theme O-GlcNAcylation 1332:1346 arg1 elevation 1319:1327 elevation 1319:1327 elevation of O-GlcNAcylation by overexpression of OGT 1319:1371 Moreover, elevation of O-GlcNAcylation by overexpression of OGT increased the expression of p300, IKKα, and IKKβ and promoted IKK-mediated activating phosphorylation of p65 at Ser-536, contributing to NF-κB activation. 28416608 1 24 theme O-linked 212:219 arg1 moiety 260:265 an O-linked β-N-acetylglucosamine (O-GlcNAc) sugar moiety 209:265 an O-linked β-N-acetylglucosamine (O-GlcNAc) sugar moiety 209:265 O-GlcNAcylation is the covalent addition of an O-linked β-N-acetylglucosamine (O-GlcNAc) sugar moiety to hydroxyl groups of serine/threonine residues of cytosolic and nuclear proteins. 28416608 0 25 theme factor 40:45 arg1 NF-κB 92:96 NF-κB 92:96 NF-κB 92:96 Hyper-O-GlcNAcylation activates nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) signaling through interplay with phosphorylation and acetylation. 28416608 0 25 theme factor 40:45 arg1 κ-light-chain-enhancer 47:68 nuclear factor κ-light-chain-enhancer 32:68 nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) signaling 32:107 Hyper-O-GlcNAcylation activates nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) signaling through interplay with phosphorylation and acetylation. 28416608 1 26 theme cytosolic 318:326 arg1 proteins 340:347 cytosolic and nuclear proteins 318:347 cytosolic and nuclear proteins 318:347 O-GlcNAcylation is the covalent addition of an O-linked β-N-acetylglucosamine (O-GlcNAc) sugar moiety to hydroxyl groups of serine/threonine residues of cytosolic and nuclear proteins. 28416608 7 27 theme O-GlcNAcylation 1038:1052 arg1 p65 1063:1065 p65 1063:1065 p65 1063:1065 In this study, we mapped O-GlcNAcylation sites of p65 at Thr-305, Ser-319, Ser-337, Thr-352, and Ser-374. 28416608 7 27 theme O-GlcNAcylation 1038:1052 arg1 sites 1054:1058 O-GlcNAcylation sites 1038:1058 O-GlcNAcylation sites of p65 1038:1065 In this study, we mapped O-GlcNAcylation sites of p65 at Thr-305, Ser-319, Ser-337, Thr-352, and Ser-374. 28416608 5 28 theme p65/RelA 866:873 arg1 acetylation 837:847 acetylation 837:847 acetylation 837:847 Recently, we and others have shown that O-GlcNAcylation affects the phosphorylation and acetylation of NF-κB subunit p65/RelA. 28416608 5 28 theme p65/RelA 866:873 arg1 phosphorylation 817:831 phosphorylation 817:831 phosphorylation 817:831 Recently, we and others have shown that O-GlcNAcylation affects the phosphorylation and acetylation of NF-κB subunit p65/RelA. 28416608 1 29 theme β-N-acetylglucosamine 221:241 arg1 moiety 260:265 an O-linked β-N-acetylglucosamine (O-GlcNAc) sugar moiety 209:265 an O-linked β-N-acetylglucosamine (O-GlcNAc) sugar moiety 209:265 O-GlcNAcylation is the covalent addition of an O-linked β-N-acetylglucosamine (O-GlcNAc) sugar moiety to hydroxyl groups of serine/threonine residues of cytosolic and nuclear proteins. 28416608 0 30 theme nuclear 32:38 arg1 NF-κB 92:96 NF-κB 92:96 NF-κB 92:96 Hyper-O-GlcNAcylation activates nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) signaling through interplay with phosphorylation and acetylation. 28416608 0 30 theme nuclear 32:38 arg1 κ-light-chain-enhancer 47:68 nuclear factor κ-light-chain-enhancer 32:68 nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) signaling 32:107 Hyper-O-GlcNAcylation activates nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) signaling through interplay with phosphorylation and acetylation. 28416608 9 31 theme IKKβ 1417:1420 arg1 expression 1387:1396 the expression 1383:1396 the expression of p300, IKKα, and IKKβ 1383:1420 Moreover, elevation of O-GlcNAcylation by overexpression of OGT increased the expression of p300, IKKα, and IKKβ and promoted IKK-mediated activating phosphorylation of p65 at Ser-536, contributing to NF-κB activation. 28416608 10 32 theme p65 1579:1581 arg1 phosphorylation 1560:1574 phosphorylation 1560:1574 phosphorylation of p65 1560:1581 In addition, we also identified phosphorylation of p65 at Thr-308, which might impair the O-GlcNAcylation of p65 at Thr-305. 28416608 3 33 theme NF-κB 568:572 arg1 activation 587:596 NF-κB constitutive activation 568:596 NF-κB constitutive activation 568:596 Aberrantly increased NF-κB O-GlcNAcylation has been linked to NF-κB constitutive activation and cancer development. 28416608 2 34 theme transcription 468:480 arg1 NF-κB 499:503 NF-κB 499:503 NF-κB 499:503 O-GlcNAcylation, analogous to phosphorylation, plays critical roles in gene expression through direct modification of transcription factors, such as NF-κB. 28416608 2 34 theme transcription 468:480 arg1 factors 482:488 transcription factors 468:488 transcription factors 468:488 O-GlcNAcylation, analogous to phosphorylation, plays critical roles in gene expression through direct modification of transcription factors, such as NF-κB. 28416608 5 35 theme NF-κB 852:856 arg1 p65/RelA 866:873 NF-κB subunit p65/RelA 852:873 NF-κB subunit p65/RelA 852:873 Recently, we and others have shown that O-GlcNAcylation affects the phosphorylation and acetylation of NF-κB subunit p65/RelA. 28416608 1 36 theme nuclear 332:338 arg1 proteins 340:347 cytosolic and nuclear proteins 318:347 cytosolic and nuclear proteins 318:347 O-GlcNAcylation is the covalent addition of an O-linked β-N-acetylglucosamine (O-GlcNAc) sugar moiety to hydroxyl groups of serine/threonine residues of cytosolic and nuclear proteins. 28416608 5 37 dep phosphorylation 817:831 arg1 the 813:815 the 813:815 the 813:815 Recently, we and others have shown that O-GlcNAcylation affects the phosphorylation and acetylation of NF-κB subunit p65/RelA. 28416608 2 38 theme gene 421:424 arg1 expression 426:435 gene expression 421:435 gene expression 421:435 O-GlcNAcylation, analogous to phosphorylation, plays critical roles in gene expression through direct modification of transcription factors, such as NF-κB. 28416608 1 39 theme O-GlcNAc 244:251 arg1 moiety 260:265 an O-linked β-N-acetylglucosamine (O-GlcNAc) sugar moiety 209:265 an O-linked β-N-acetylglucosamine (O-GlcNAc) sugar moiety 209:265 O-GlcNAcylation is the covalent addition of an O-linked β-N-acetylglucosamine (O-GlcNAc) sugar moiety to hydroxyl groups of serine/threonine residues of cytosolic and nuclear proteins. 28416608 0 40 theme κ-light-chain-enhancer 47:68 arg1 signaling 99:107 nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) signaling 32:107 nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) signaling 32:107 Hyper-O-GlcNAcylation activates nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) signaling through interplay with phosphorylation and acetylation. 28416608 1 41 theme proteins 340:347 arg1 proteins 340:347 cytosolic and nuclear proteins 318:347 cytosolic and nuclear proteins 318:347 O-GlcNAcylation is the covalent addition of an O-linked β-N-acetylglucosamine (O-GlcNAc) sugar moiety to hydroxyl groups of serine/threonine residues of cytosolic and nuclear proteins. 28416608 1 41 theme proteins 340:347 arg1 residues 306:313 serine/threonine residues 289:313 serine/threonine residues of cytosolic and nuclear proteins 289:347 O-GlcNAcylation is the covalent addition of an O-linked β-N-acetylglucosamine (O-GlcNAc) sugar moiety to hydroxyl groups of serine/threonine residues of cytosolic and nuclear proteins. 28416608 5 42 theme subunit 858:864 arg1 p65/RelA 866:873 NF-κB subunit p65/RelA 852:873 NF-κB subunit p65/RelA 852:873 Recently, we and others have shown that O-GlcNAcylation affects the phosphorylation and acetylation of NF-κB subunit p65/RelA. 28416608 8 43 from Thr-305 1145:1151 arg1 O-GlcNAcylation 1119:1133 O-GlcNAcylation 1119:1133 O-GlcNAcylation of p65 at Thr-305 and Ser-319 1119:1163 O-GlcNAcylation of p65 at Thr-305 and Ser-319 increased CREB-binding protein (CBP)/p300-dependent activating acetylation of p65 at Lys-310, contributing to NF-κB transcriptional activation. 28416608 4 44 theme molecular 702:710 arg1 mechanisms 712:721 the molecular mechanisms 698:721 the molecular mechanisms that tune NF-κB activity 698:746 Therefore, it is of a great biological and clinical significance to dissect the molecular mechanisms that tune NF-κB activity. 28416608 0 45 theme B 83:83 arg1 cells 85:89 activated B cells 73:89 activated B cells 73:89 Hyper-O-GlcNAcylation activates nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) signaling through interplay with phosphorylation and acetylation. 28416608 9 46 theme IKK-mediated 1435:1446 arg1 phosphorylation 1459:1473 IKK-mediated activating phosphorylation 1435:1473 IKK-mediated activating phosphorylation of p65 at Ser-536, contributing to NF-κB activation 1435:1525 Moreover, elevation of O-GlcNAcylation by overexpression of OGT increased the expression of p300, IKKα, and IKKβ and promoted IKK-mediated activating phosphorylation of p65 at Ser-536, contributing to NF-κB activation. 28416608 8 47 theme NF-κB 1275:1279 arg1 activation 1297:1306 NF-κB transcriptional activation 1275:1306 NF-κB transcriptional activation 1275:1306 O-GlcNAcylation of p65 at Thr-305 and Ser-319 increased CREB-binding protein (CBP)/p300-dependent activating acetylation of p65 at Lys-310, contributing to NF-κB transcriptional activation. 28416608 6 48 theme NF-κB 932:936 arg1 signaling 938:946 NF-κB signaling 932:946 NF-κB signaling 932:946 However, the mechanism of how O-GlcNAcylation activates NF-κB signaling through phosphorylation and acetylation is not fully understood. 28416608 11 49 theme NF-κB 1762:1766 arg1 signaling 1768:1776 NF-κB signaling 1762:1776 NF-κB signaling 1762:1776 These results indicate mechanisms through which both non-pathological and oncogenic O-GlcNAcylation regulate NF-κB signaling through interplay with phosphorylation and acetylation. 28416608 0 50 theme activated 73:81 arg1 cells 85:89 activated B cells 73:89 activated B cells 73:89 Hyper-O-GlcNAcylation activates nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) signaling through interplay with phosphorylation and acetylation. 28416608 9 51 theme activating 1448:1457 arg1 phosphorylation 1459:1473 IKK-mediated activating phosphorylation 1435:1473 IKK-mediated activating phosphorylation of p65 at Ser-536, contributing to NF-κB activation 1435:1525 Moreover, elevation of O-GlcNAcylation by overexpression of OGT increased the expression of p300, IKKα, and IKKβ and promoted IKK-mediated activating phosphorylation of p65 at Ser-536, contributing to NF-κB activation. 28416608 9 52 from Ser-536 1485:1491 arg1 phosphorylation 1459:1473 IKK-mediated activating phosphorylation 1435:1473 IKK-mediated activating phosphorylation of p65 at Ser-536, contributing to NF-κB activation 1435:1525 Moreover, elevation of O-GlcNAcylation by overexpression of OGT increased the expression of p300, IKKα, and IKKβ and promoted IKK-mediated activating phosphorylation of p65 at Ser-536, contributing to NF-κB activation. 28416608 4 53 theme biological 650:659 arg1 significance 674:685 a great biological and clinical significance 642:685 a great biological and clinical significance 642:685 Therefore, it is of a great biological and clinical significance to dissect the molecular mechanisms that tune NF-κB activity. 28416608 4 54 theme NF-κB 733:737 arg1 activity 739:746 NF-κB activity 733:746 NF-κB activity 733:746 Therefore, it is of a great biological and clinical significance to dissect the molecular mechanisms that tune NF-κB activity. 28416608 11 55 theme non-pathological 1706:1721 arg1 O-GlcNAcylation 1737:1751 both non-pathological and oncogenic O-GlcNAcylation 1701:1751 both non-pathological and oncogenic O-GlcNAcylation 1701:1751 These results indicate mechanisms through which both non-pathological and oncogenic O-GlcNAcylation regulate NF-κB signaling through interplay with phosphorylation and acetylation. 28416608 1 56 theme sugar 254:258 arg1 moiety 260:265 an O-linked β-N-acetylglucosamine (O-GlcNAc) sugar moiety 209:265 an O-linked β-N-acetylglucosamine (O-GlcNAc) sugar moiety 209:265 O-GlcNAcylation is the covalent addition of an O-linked β-N-acetylglucosamine (O-GlcNAc) sugar moiety to hydroxyl groups of serine/threonine residues of cytosolic and nuclear proteins. 28416608 8 57 theme protein 1188:1194 arg1 acetylation 1228:1238 CREB-binding protein (CBP)/p300-dependent activating acetylation 1175:1238 CREB-binding protein (CBP)/p300-dependent activating acetylation of p65 1175:1245 O-GlcNAcylation of p65 at Thr-305 and Ser-319 increased CREB-binding protein (CBP)/p300-dependent activating acetylation of p65 at Lys-310, contributing to NF-κB transcriptional activation. 28416608 3 58 attach linked 558:563 arg1 development 609:619 cancer development 602:619 cancer development 602:619 Aberrantly increased NF-κB O-GlcNAcylation has been linked to NF-κB constitutive activation and cancer development. 28416608 3 58 attach linked 558:563 arg2 O-GlcNAcylation 533:547 Aberrantly increased NF-κB O-GlcNAcylation 506:547 Aberrantly increased NF-κB O-GlcNAcylation 506:547 Aberrantly increased NF-κB O-GlcNAcylation has been linked to NF-κB constitutive activation and cancer development. 28416608 3 58 attach linked 558:563 arg1 activation 587:596 NF-κB constitutive activation 568:596 NF-κB constitutive activation 568:596 Aberrantly increased NF-κB O-GlcNAcylation has been linked to NF-κB constitutive activation and cancer development. 28416608 2 59 theme analogous 367:375 arg1 O-GlcNAcylation 350:364 O-GlcNAcylation 350:364 O-GlcNAcylation 350:364 O-GlcNAcylation, analogous to phosphorylation, plays critical roles in gene expression through direct modification of transcription factors, such as NF-κB. 28416608 1 60 theme moiety 260:265 arg1 addition 197:204 the covalent addition 184:204 the covalent addition of an O-linked β-N-acetylglucosamine (O-GlcNAc) sugar moiety to hydroxyl groups of serine/threonine residues of cytosolic and nuclear proteins 184:347 O-GlcNAcylation is the covalent addition of an O-linked β-N-acetylglucosamine (O-GlcNAc) sugar moiety to hydroxyl groups of serine/threonine residues of cytosolic and nuclear proteins. 28416608 1 60 theme moiety 260:265 arg1 O-GlcNAcylation 165:179 O-GlcNAcylation 165:179 O-GlcNAcylation 165:179 O-GlcNAcylation is the covalent addition of an O-linked β-N-acetylglucosamine (O-GlcNAc) sugar moiety to hydroxyl groups of serine/threonine residues of cytosolic and nuclear proteins. 28416608 10 61 from Thr-305 1644:1650 arg1 O-GlcNAcylation 1618:1632 the O-GlcNAcylation 1614:1632 the O-GlcNAcylation of p65 at Thr-305 1614:1650 In addition, we also identified phosphorylation of p65 at Thr-308, which might impair the O-GlcNAcylation of p65 at Thr-305. 28416608 2 62 theme factors 482:488 arg1 modification 452:463 direct modification 445:463 direct modification of transcription factors, such as NF-κB 445:503 O-GlcNAcylation, analogous to phosphorylation, plays critical roles in gene expression through direct modification of transcription factors, such as NF-κB. 28416608 3 63 theme constitutive 574:585 arg1 activation 587:596 NF-κB constitutive activation 568:596 NF-κB constitutive activation 568:596 Aberrantly increased NF-κB O-GlcNAcylation has been linked to NF-κB constitutive activation and cancer development. 28416608 11 64 with interplay 1786:1794 arg1 acetylation 1821:1831 acetylation 1821:1831 acetylation 1821:1831 These results indicate mechanisms through which both non-pathological and oncogenic O-GlcNAcylation regulate NF-κB signaling through interplay with phosphorylation and acetylation. 28416608 11 64 with interplay 1786:1794 arg1 phosphorylation 1801:1815 phosphorylation 1801:1815 phosphorylation 1801:1815 These results indicate mechanisms through which both non-pathological and oncogenic O-GlcNAcylation regulate NF-κB signaling through interplay with phosphorylation and acetylation. 28416608 4 65 theme great 644:648 arg1 significance 674:685 a great biological and clinical significance 642:685 a great biological and clinical significance 642:685 Therefore, it is of a great biological and clinical significance to dissect the molecular mechanisms that tune NF-κB activity. 28416608 0 66 theme cells 85:89 arg1 NF-κB 92:96 NF-κB 92:96 NF-κB 92:96 Hyper-O-GlcNAcylation activates nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) signaling through interplay with phosphorylation and acetylation. 28416608 0 66 theme cells 85:89 arg1 κ-light-chain-enhancer 47:68 nuclear factor κ-light-chain-enhancer 32:68 nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) signaling 32:107 Hyper-O-GlcNAcylation activates nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) signaling through interplay with phosphorylation and acetylation. 28416608 9 67 theme OGT 1369:1371 arg1 overexpression 1351:1364 overexpression 1351:1364 overexpression of OGT 1351:1371 Moreover, elevation of O-GlcNAcylation by overexpression of OGT increased the expression of p300, IKKα, and IKKβ and promoted IKK-mediated activating phosphorylation of p65 at Ser-536, contributing to NF-κB activation. 28416608 7 68 theme p65 1063:1065 arg1 p65 1063:1065 p65 1063:1065 p65 1063:1065 In this study, we mapped O-GlcNAcylation sites of p65 at Thr-305, Ser-319, Ser-337, Thr-352, and Ser-374. 28416608 7 68 theme p65 1063:1065 arg1 sites 1054:1058 O-GlcNAcylation sites 1038:1058 O-GlcNAcylation sites of p65 1038:1065 In this study, we mapped O-GlcNAcylation sites of p65 at Thr-305, Ser-319, Ser-337, Thr-352, and Ser-374. 28416608 4 69 theme clinical 665:672 arg1 significance 674:685 a great biological and clinical significance 642:685 a great biological and clinical significance 642:685 Therefore, it is of a great biological and clinical significance to dissect the molecular mechanisms that tune NF-κB activity. 28416608 1 70 theme hydroxyl 270:277 arg1 proteins 340:347 cytosolic and nuclear proteins 318:347 cytosolic and nuclear proteins 318:347 O-GlcNAcylation is the covalent addition of an O-linked β-N-acetylglucosamine (O-GlcNAc) sugar moiety to hydroxyl groups of serine/threonine residues of cytosolic and nuclear proteins. 28416608 1 70 theme hydroxyl 270:277 arg1 groups 279:284 hydroxyl groups 270:284 hydroxyl groups of serine/threonine residues of cytosolic and nuclear proteins 270:347 O-GlcNAcylation is the covalent addition of an O-linked β-N-acetylglucosamine (O-GlcNAc) sugar moiety to hydroxyl groups of serine/threonine residues of cytosolic and nuclear proteins. 28416608 1 70 theme hydroxyl 270:277 arg1 residues 306:313 serine/threonine residues 289:313 serine/threonine residues of cytosolic and nuclear proteins 289:347 O-GlcNAcylation is the covalent addition of an O-linked β-N-acetylglucosamine (O-GlcNAc) sugar moiety to hydroxyl groups of serine/threonine residues of cytosolic and nuclear proteins. 28142197 3 0 theme 4 555:555 arg1 glucosylation 564:576 3, 4' and 7 glucosylation 552:576 3, 4' and 7 glucosylation in flavonoids 552:590 Previous work has shown TnBgl1A to hydrolyse 3, 4' and 7 glucosylation in flavonoids, and although conversion of 3-glucosylated substrate to aglycone was low, it was improved by mutagenesis of residue N220. 28142197 8 1 theme hydrolytic 1561:1570 arg1 activity 1572:1579 hydrolytic activity 1561:1579 hydrolytic activity on 3-glucosylated flavonoids 1561:1608 Residue W322 was proven important for substrate accomodation, as mutagenesis to W322A resulted in a large reduction of hydrolytic activity on 3-glucosylated flavonoids. 28142197 11 2 theme molecular 1959:1967 arg1 understanding 1969:1981 the molecular understanding 1955:1981 the molecular understanding of activity in GH1 enzymes 1955:2008 This work pinpoints positions in the aglycone region of TnBgl1A of importance for specificity on flavonoid-3-glucosides, improving the molecular understanding of activity in GH1 enzymes. 28142197 9 3 theme glucoside 1621:1629 arg1 hydrolysis 1631:1640 Flavonoid glucoside hydrolysis 1611:1640 Flavonoid glucoside hydrolysis 1611:1640 Flavonoid glucoside hydrolysis was unaffected by mutations at positions 224 and 310. 28142197 1 4 theme terminal 203:210 arg1 bonds 225:229 O-linked terminal β-glycosidic bonds 194:229 O-linked terminal β-glycosidic bonds 194:229 The β-glucosidase TnBgl1A catalyses hydrolysis of O-linked terminal β-glycosidic bonds at the nonreducing end of glycosides/oligosaccharides. 28142197 3 5 theme 3-glucosylated 620:633 arg1 substrate 635:643 3-glucosylated substrate 620:643 3-glucosylated substrate 620:643 Previous work has shown TnBgl1A to hydrolyse 3, 4' and 7 glucosylation in flavonoids, and although conversion of 3-glucosylated substrate to aglycone was low, it was improved by mutagenesis of residue N220. 28142197 2 6 theme lignocellulose 334:347 arg1 conversion 349:358 lignocellulose conversion 334:358 lignocellulose conversion (degrading cellobiose to glucose) 334:392 Enzymes with this specificity have potential in lignocellulose conversion (degrading cellobiose to glucose) and conversion of bioactive flavonoids (modification of glycosylation results in modulation of bioavailability). 28142197 1 7 theme bonds 225:229 arg1 hydrolysis 180:189 hydrolysis 180:189 hydrolysis of O-linked terminal β-glycosidic bonds 180:229 The β-glucosidase TnBgl1A catalyses hydrolysis of O-linked terminal β-glycosidic bonds at the nonreducing end of glycosides/oligosaccharides. 28142197 6 8 theme glucosylated 1157:1168 arg1 flavonoids 1170:1179 eight glucosylated flavonoids 1151:1179 eight glucosylated flavonoids 1151:1179 Activity screening was made on eight glucosylated flavonoids, and kinetic parameters were monitored for the flavonoid quercetin-3-glucoside (Q3), as well as for the model substrate para-nitrophenyl-β-d-glucopyranoside (pNPGlc). 28142197 11 9 from specificity 1906:1916 arg1 flavonoid-3-glucosides 1921:1942 flavonoid-3-glucosides 1921:1942 flavonoid-3-glucosides 1921:1942 This work pinpoints positions in the aglycone region of TnBgl1A of importance for specificity on flavonoid-3-glucosides, improving the molecular understanding of activity in GH1 enzymes. 28142197 0 10 theme glucosides 132:141 arg1 hydrolysis 108:117 hydrolysis 108:117 hydrolysis of flavonoid glucosides 108:141 Crystal structure of β-glucosidase 1A from Thermotoga neapolitana and comparison of active site mutants for hydrolysis of flavonoid glucosides. 28142197 4 11 theme interacting 939:949 arg1 residues 951:958 substrate interacting residues 929:958 substrate interacting residues 929:958 To further explore structure-function relationships, the crystal structure of the nucleophile mutant TnBgl1A-E349G was determined at 1.9 Å resolution, and docking studies of flavonoid substrates were made to reveal substrate interacting residues. 28142197 6 12 theme flavonoid 1228:1236 arg1 quercetin-3-glucoside 1238:1258 the flavonoid quercetin-3-glucoside 1224:1258 the flavonoid quercetin-3-glucoside (Q3) 1224:1263 Activity screening was made on eight glucosylated flavonoids, and kinetic parameters were monitored for the flavonoid quercetin-3-glucoside (Q3), as well as for the model substrate para-nitrophenyl-β-d-glucopyranoside (pNPGlc). 28142197 6 12 theme flavonoid 1228:1236 arg1 Q3 1261:1262 Q3 1261:1262 Q3 1261:1262 Activity screening was made on eight glucosylated flavonoids, and kinetic parameters were monitored for the flavonoid quercetin-3-glucoside (Q3), as well as for the model substrate para-nitrophenyl-β-d-glucopyranoside (pNPGlc). 28142197 10 13 theme thermal 1739:1745 arg1 stability 1747:1755 thermal stability 1739:1755 thermal stability 1739:1755 The mutations did not significantly affect thermal stability, and the variants kept an apparent unfolding temperature of 101°C. 28142197 5 14 theme single 973:978 arg1 changes 991:997 single amino acid changes 973:997 single amino acid changes 973:997 A series of single amino acid changes were introduced in the aglycone binding region [N220(S/F), N221(S/F), F224(I), F310(L/E), and W322(A)] of the wild type. 28142197 6 15 theme Activity 1120:1127 arg1 screening 1129:1137 Activity screening 1120:1137 Activity screening 1120:1137 Activity screening was made on eight glucosylated flavonoids, and kinetic parameters were monitored for the flavonoid quercetin-3-glucoside (Q3), as well as for the model substrate para-nitrophenyl-β-d-glucopyranoside (pNPGlc). 28142197 11 16 from positions 1844:1852 arg1 region 1870:1875 the aglycone region 1857:1875 the aglycone region of TnBgl1A of importance for specificity on flavonoid-3-glucosides 1857:1942 This work pinpoints positions in the aglycone region of TnBgl1A of importance for specificity on flavonoid-3-glucosides, improving the molecular understanding of activity in GH1 enzymes. 28142197 1 17 theme β-glucosidase 148:160 arg1 TnBgl1A 162:168 The β-glucosidase TnBgl1A 144:168 The β-glucosidase TnBgl1A 144:168 The β-glucosidase TnBgl1A catalyses hydrolysis of O-linked terminal β-glycosidic bonds at the nonreducing end of glycosides/oligosaccharides. 28142197 9 18 from positions 1673:1681 arg1 mutations 1660:1668 mutations 1660:1668 mutations at positions 224 and 310 1660:1693 Flavonoid glucoside hydrolysis was unaffected by mutations at positions 224 and 310. 28142197 3 19 from glucosylation 564:576 arg1 flavonoids 581:590 flavonoids 581:590 flavonoids 581:590 Previous work has shown TnBgl1A to hydrolyse 3, 4' and 7 glucosylation in flavonoids, and although conversion of 3-glucosylated substrate to aglycone was low, it was improved by mutagenesis of residue N220. 28142197 6 20 theme model 1285:1289 arg1 pNPGlc 1339:1344 pNPGlc 1339:1344 pNPGlc 1339:1344 Activity screening was made on eight glucosylated flavonoids, and kinetic parameters were monitored for the flavonoid quercetin-3-glucoside (Q3), as well as for the model substrate para-nitrophenyl-β-d-glucopyranoside (pNPGlc). 28142197 6 20 theme model 1285:1289 arg1 para-nitrophenyl-β-d-glucopyranoside 1301:1336 the model substrate para-nitrophenyl-β-d-glucopyranoside 1281:1336 the model substrate para-nitrophenyl-β-d-glucopyranoside (pNPGlc) 1281:1345 Activity screening was made on eight glucosylated flavonoids, and kinetic parameters were monitored for the flavonoid quercetin-3-glucoside (Q3), as well as for the model substrate para-nitrophenyl-β-d-glucopyranoside (pNPGlc). 28142197 4 21 theme mutant 808:813 arg1 TnBgl1A-E349G 815:827 the nucleophile mutant TnBgl1A-E349G 792:827 the nucleophile mutant TnBgl1A-E349G 792:827 To further explore structure-function relationships, the crystal structure of the nucleophile mutant TnBgl1A-E349G was determined at 1.9 Å resolution, and docking studies of flavonoid substrates were made to reveal substrate interacting residues. 28142197 0 22 theme site 91:94 arg1 mutants 96:102 active site mutants 84:102 active site mutants 84:102 Crystal structure of β-glucosidase 1A from Thermotoga neapolitana and comparison of active site mutants for hydrolysis of flavonoid glucosides. 28142197 8 23 theme Residue 1442:1448 arg1 W322 1450:1453 Residue W322 1442:1453 Residue W322 1442:1453 Residue W322 was proven important for substrate accomodation, as mutagenesis to W322A resulted in a large reduction of hydrolytic activity on 3-glucosylated flavonoids. 28142197 1 24 link O-linked 194:201 arg1 bonds 225:229 O-linked terminal β-glycosidic bonds 194:229 O-linked terminal β-glycosidic bonds 194:229 The β-glucosidase TnBgl1A catalyses hydrolysis of O-linked terminal β-glycosidic bonds at the nonreducing end of glycosides/oligosaccharides. 28142197 5 25 theme aglycone 1022:1029 arg1 region 1039:1044 the aglycone binding region [N220 1018:1050 the aglycone binding region [N220(S/F) 1018:1055 A series of single amino acid changes were introduced in the aglycone binding region [N220(S/F), N221(S/F), F224(I), F310(L/E), and W322(A)] of the wild type. 28142197 5 25 theme aglycone 1022:1029 arg1 S/F 1052:1054 S/F 1052:1054 S/F 1052:1054 A series of single amino acid changes were introduced in the aglycone binding region [N220(S/F), N221(S/F), F224(I), F310(L/E), and W322(A)] of the wild type. 28142197 0 26 theme Crystal 0:6 arg1 structure 8:16 Crystal structure 0:16 Crystal structure of β-glucosidase 1A from Thermotoga neapolitana and comparison of active site mutants for hydrolysis of flavonoid glucosides. 0:142 Crystal structure of β-glucosidase 1A from Thermotoga neapolitana and comparison of active site mutants for hydrolysis of flavonoid glucosides. 28142197 5 27 theme acid 986:989 arg1 changes 991:997 single amino acid changes 973:997 single amino acid changes 973:997 A series of single amino acid changes were introduced in the aglycone binding region [N220(S/F), N221(S/F), F224(I), F310(L/E), and W322(A)] of the wild type. 28142197 2 28 theme bioavailability 489:503 arg1 modulation 475:484 modulation 475:484 modulation of bioavailability 475:503 Enzymes with this specificity have potential in lignocellulose conversion (degrading cellobiose to glucose) and conversion of bioactive flavonoids (modification of glycosylation results in modulation of bioavailability). 28142197 11 29 theme importance 1891:1900 arg1 TnBgl1A 1880:1886 TnBgl1A 1880:1886 TnBgl1A of importance for specificity on flavonoid-3-glucosides 1880:1942 This work pinpoints positions in the aglycone region of TnBgl1A of importance for specificity on flavonoid-3-glucosides, improving the molecular understanding of activity in GH1 enzymes. 28142197 5 30 theme wild 1109:1112 arg1 type 1114:1117 the wild type 1105:1117 the wild type 1105:1117 A series of single amino acid changes were introduced in the aglycone binding region [N220(S/F), N221(S/F), F224(I), F310(L/E), and W322(A)] of the wild type. 28142197 8 31 theme substrate 1480:1488 arg1 accomodation 1490:1501 substrate accomodation 1480:1501 substrate accomodation 1480:1501 Residue W322 was proven important for substrate accomodation, as mutagenesis to W322A resulted in a large reduction of hydrolytic activity on 3-glucosylated flavonoids. 28142197 3 32 theme Previous 507:514 arg1 work 516:519 Previous work 507:519 Previous work 507:519 Previous work has shown TnBgl1A to hydrolyse 3, 4' and 7 glucosylation in flavonoids, and although conversion of 3-glucosylated substrate to aglycone was low, it was improved by mutagenesis of residue N220. 28142197 11 33 theme aglycone 1861:1868 arg1 region 1870:1875 the aglycone region 1857:1875 the aglycone region of TnBgl1A of importance for specificity on flavonoid-3-glucosides 1857:1942 This work pinpoints positions in the aglycone region of TnBgl1A of importance for specificity on flavonoid-3-glucosides, improving the molecular understanding of activity in GH1 enzymes. 28142197 0 34 theme 1A 35:36 arg1 structure 8:16 Crystal structure 0:16 Crystal structure of β-glucosidase 1A from Thermotoga neapolitana and comparison of active site mutants for hydrolysis of flavonoid glucosides. 0:142 Crystal structure of β-glucosidase 1A from Thermotoga neapolitana and comparison of active site mutants for hydrolysis of flavonoid glucosides. 28142197 10 35 theme apparent 1783:1790 arg1 temperature 1802:1812 an apparent unfolding temperature 1780:1812 an apparent unfolding temperature of 101°C 1780:1821 The mutations did not significantly affect thermal stability, and the variants kept an apparent unfolding temperature of 101°C. 28142197 4 36 theme docking 869:875 arg1 studies 877:883 docking studies 869:883 docking studies of flavonoid substrates 869:907 To further explore structure-function relationships, the crystal structure of the nucleophile mutant TnBgl1A-E349G was determined at 1.9 Å resolution, and docking studies of flavonoid substrates were made to reveal substrate interacting residues. 28142197 0 37 theme Thermotoga 43:52 arg1 neapolitana 54:64 Thermotoga neapolitana 43:64 Thermotoga neapolitana 43:64 Crystal structure of β-glucosidase 1A from Thermotoga neapolitana and comparison of active site mutants for hydrolysis of flavonoid glucosides. 28142197 11 38 from activity 1986:1993 arg1 enzymes 2002:2008 GH1 enzymes 1998:2008 GH1 enzymes 1998:2008 This work pinpoints positions in the aglycone region of TnBgl1A of importance for specificity on flavonoid-3-glucosides, improving the molecular understanding of activity in GH1 enzymes. 28142197 8 39 theme activity 1572:1579 arg1 reduction 1548:1556 a large reduction 1540:1556 a large reduction of hydrolytic activity on 3-glucosylated flavonoids 1540:1608 Residue W322 was proven important for substrate accomodation, as mutagenesis to W322A resulted in a large reduction of hydrolytic activity on 3-glucosylated flavonoids. 28142197 1 40 theme nonreducing 238:248 arg1 end 250:252 the nonreducing end 234:252 the nonreducing end of glycosides/oligosaccharides 234:283 The β-glucosidase TnBgl1A catalyses hydrolysis of O-linked terminal β-glycosidic bonds at the nonreducing end of glycosides/oligosaccharides. 28142197 9 41 from 310 1691:1693 arg1 mutations 1660:1668 mutations 1660:1668 mutations at positions 224 and 310 1660:1693 Flavonoid glucoside hydrolysis was unaffected by mutations at positions 224 and 310. 28142197 2 42 from results 464:470 arg1 modulation 475:484 modulation 475:484 modulation of bioavailability 475:503 Enzymes with this specificity have potential in lignocellulose conversion (degrading cellobiose to glucose) and conversion of bioactive flavonoids (modification of glycosylation results in modulation of bioavailability). 28142197 10 43 theme 101°C 1817:1821 arg1 temperature 1802:1812 an apparent unfolding temperature 1780:1812 an apparent unfolding temperature of 101°C 1780:1821 The mutations did not significantly affect thermal stability, and the variants kept an apparent unfolding temperature of 101°C. 28142197 4 44 theme Å 851:851 arg1 resolution 853:862 1.9 Å resolution 847:862 1.9 Å resolution 847:862 To further explore structure-function relationships, the crystal structure of the nucleophile mutant TnBgl1A-E349G was determined at 1.9 Å resolution, and docking studies of flavonoid substrates were made to reveal substrate interacting residues. 28142197 2 45 theme bioactive 412:420 arg1 flavonoids 422:431 bioactive flavonoids 412:431 bioactive flavonoids (modification of glycosylation results in modulation of bioavailability) 412:504 Enzymes with this specificity have potential in lignocellulose conversion (degrading cellobiose to glucose) and conversion of bioactive flavonoids (modification of glycosylation results in modulation of bioavailability). 28142197 8 46 theme 3-glucosylated 1584:1597 arg1 flavonoids 1599:1608 3-glucosylated flavonoids 1584:1608 3-glucosylated flavonoids 1584:1608 Residue W322 was proven important for substrate accomodation, as mutagenesis to W322A resulted in a large reduction of hydrolytic activity on 3-glucosylated flavonoids. 28142197 2 47 from modulation 475:484 arg1 modification 434:445 modification 434:445 modification of glycosylation results in modulation of bioavailability 434:503 Enzymes with this specificity have potential in lignocellulose conversion (degrading cellobiose to glucose) and conversion of bioactive flavonoids (modification of glycosylation results in modulation of bioavailability). 28142197 6 48 theme substrate 1291:1299 arg1 pNPGlc 1339:1344 pNPGlc 1339:1344 pNPGlc 1339:1344 Activity screening was made on eight glucosylated flavonoids, and kinetic parameters were monitored for the flavonoid quercetin-3-glucoside (Q3), as well as for the model substrate para-nitrophenyl-β-d-glucopyranoside (pNPGlc). 28142197 6 48 theme substrate 1291:1299 arg1 para-nitrophenyl-β-d-glucopyranoside 1301:1336 the model substrate para-nitrophenyl-β-d-glucopyranoside 1281:1336 the model substrate para-nitrophenyl-β-d-glucopyranoside (pNPGlc) 1281:1345 Activity screening was made on eight glucosylated flavonoids, and kinetic parameters were monitored for the flavonoid quercetin-3-glucoside (Q3), as well as for the model substrate para-nitrophenyl-β-d-glucopyranoside (pNPGlc). 28142197 7 49 theme catalytic 1398:1406 arg1 efficiency 1408:1417 the catalytic efficiency 1394:1417 the catalytic efficiency on both pNPGlc and Q3 1394:1439 Substitution by Ser at N220 or N221 increased the catalytic efficiency on both pNPGlc and Q3. 28142197 4 50 theme substrates 898:907 arg1 studies 877:883 docking studies 869:883 docking studies of flavonoid substrates 869:907 To further explore structure-function relationships, the crystal structure of the nucleophile mutant TnBgl1A-E349G was determined at 1.9 Å resolution, and docking studies of flavonoid substrates were made to reveal substrate interacting residues. 28142197 11 51 from understanding 1969:1981 arg1 enzymes 2002:2008 GH1 enzymes 1998:2008 GH1 enzymes 1998:2008 This work pinpoints positions in the aglycone region of TnBgl1A of importance for specificity on flavonoid-3-glucosides, improving the molecular understanding of activity in GH1 enzymes. 28142197 8 52 theme large 1542:1546 arg1 reduction 1548:1556 a large reduction 1540:1556 a large reduction of hydrolytic activity on 3-glucosylated flavonoids 1540:1608 Residue W322 was proven important for substrate accomodation, as mutagenesis to W322A resulted in a large reduction of hydrolytic activity on 3-glucosylated flavonoids. 28142197 6 53 theme kinetic 1186:1192 arg1 parameters 1194:1203 kinetic parameters 1186:1203 kinetic parameters 1186:1203 Activity screening was made on eight glucosylated flavonoids, and kinetic parameters were monitored for the flavonoid quercetin-3-glucoside (Q3), as well as for the model substrate para-nitrophenyl-β-d-glucopyranoside (pNPGlc). 28142197 3 54 theme 7 562:562 arg1 glucosylation 564:576 3, 4' and 7 glucosylation 552:576 3, 4' and 7 glucosylation in flavonoids 552:590 Previous work has shown TnBgl1A to hydrolyse 3, 4' and 7 glucosylation in flavonoids, and although conversion of 3-glucosylated substrate to aglycone was low, it was improved by mutagenesis of residue N220. 28142197 9 55 theme Flavonoid 1611:1619 arg1 hydrolysis 1631:1640 Flavonoid glucoside hydrolysis 1611:1640 Flavonoid glucoside hydrolysis 1611:1640 Flavonoid glucoside hydrolysis was unaffected by mutations at positions 224 and 310. 28142197 11 56 theme GH1 1998:2000 arg1 enzymes 2002:2008 GH1 enzymes 1998:2008 GH1 enzymes 1998:2008 This work pinpoints positions in the aglycone region of TnBgl1A of importance for specificity on flavonoid-3-glucosides, improving the molecular understanding of activity in GH1 enzymes. 28142197 1 57 theme O-linked 194:201 arg1 bonds 225:229 O-linked terminal β-glycosidic bonds 194:229 O-linked terminal β-glycosidic bonds 194:229 The β-glucosidase TnBgl1A catalyses hydrolysis of O-linked terminal β-glycosidic bonds at the nonreducing end of glycosides/oligosaccharides. 28142197 7 58 from N221 1379:1382 arg1 Substitution 1348:1359 Substitution 1348:1359 Substitution by Ser at N220 or N221 1348:1382 Substitution by Ser at N220 or N221 increased the catalytic efficiency on both pNPGlc and Q3. 28142197 4 59 theme flavonoid 888:896 arg1 substrates 898:907 flavonoid substrates 888:907 flavonoid substrates 888:907 To further explore structure-function relationships, the crystal structure of the nucleophile mutant TnBgl1A-E349G was determined at 1.9 Å resolution, and docking studies of flavonoid substrates were made to reveal substrate interacting residues. 28142197 0 60 theme flavonoid 122:130 arg1 glucosides 132:141 flavonoid glucosides 122:141 flavonoid glucosides 122:141 Crystal structure of β-glucosidase 1A from Thermotoga neapolitana and comparison of active site mutants for hydrolysis of flavonoid glucosides. 28142197 11 61 theme activity 1986:1993 arg1 understanding 1969:1981 the molecular understanding 1955:1981 the molecular understanding of activity in GH1 enzymes 1955:2008 This work pinpoints positions in the aglycone region of TnBgl1A of importance for specificity on flavonoid-3-glucosides, improving the molecular understanding of activity in GH1 enzymes. 28142197 1 62 theme β-glycosidic 212:223 arg1 bonds 225:229 O-linked terminal β-glycosidic bonds 194:229 O-linked terminal β-glycosidic bonds 194:229 The β-glucosidase TnBgl1A catalyses hydrolysis of O-linked terminal β-glycosidic bonds at the nonreducing end of glycosides/oligosaccharides. 28142197 3 63 theme substrate 635:643 arg1 conversion 606:615 conversion 606:615 conversion of 3-glucosylated substrate to aglycone 606:655 Previous work has shown TnBgl1A to hydrolyse 3, 4' and 7 glucosylation in flavonoids, and although conversion of 3-glucosylated substrate to aglycone was low, it was improved by mutagenesis of residue N220. 28142197 7 64 from efficiency 1408:1417 arg1 Q3 1438:1439 Q3 1438:1439 Q3 1438:1439 Substitution by Ser at N220 or N221 increased the catalytic efficiency on both pNPGlc and Q3. 28142197 7 64 from efficiency 1408:1417 arg1 pNPGlc 1427:1432 pNPGlc 1427:1432 pNPGlc 1427:1432 Substitution by Ser at N220 or N221 increased the catalytic efficiency on both pNPGlc and Q3. 28142197 2 65 with Enzymes 286:292 arg1 specificity 304:314 this specificity 299:314 this specificity 299:314 Enzymes with this specificity have potential in lignocellulose conversion (degrading cellobiose to glucose) and conversion of bioactive flavonoids (modification of glycosylation results in modulation of bioavailability). 28142197 0 66 from comparison 70:79 arg1 structure 8:16 Crystal structure 0:16 Crystal structure of β-glucosidase 1A from Thermotoga neapolitana and comparison of active site mutants for hydrolysis of flavonoid glucosides. 0:142 Crystal structure of β-glucosidase 1A from Thermotoga neapolitana and comparison of active site mutants for hydrolysis of flavonoid glucosides. 28142197 4 67 theme substrate 929:937 arg1 residues 951:958 substrate interacting residues 929:958 substrate interacting residues 929:958 To further explore structure-function relationships, the crystal structure of the nucleophile mutant TnBgl1A-E349G was determined at 1.9 Å resolution, and docking studies of flavonoid substrates were made to reveal substrate interacting residues. 28142197 4 68 theme structure-function 733:750 arg1 relationships 752:764 structure-function relationships 733:764 structure-function relationships 733:764 To further explore structure-function relationships, the crystal structure of the nucleophile mutant TnBgl1A-E349G was determined at 1.9 Å resolution, and docking studies of flavonoid substrates were made to reveal substrate interacting residues. 28142197 8 69 from reduction 1548:1556 arg1 flavonoids 1599:1608 3-glucosylated flavonoids 1584:1608 3-glucosylated flavonoids 1584:1608 Residue W322 was proven important for substrate accomodation, as mutagenesis to W322A resulted in a large reduction of hydrolytic activity on 3-glucosylated flavonoids. 28142197 8 70 from flavonoids 1599:1608 arg1 reduction 1548:1556 a large reduction 1540:1556 a large reduction of hydrolytic activity on 3-glucosylated flavonoids 1540:1608 Residue W322 was proven important for substrate accomodation, as mutagenesis to W322A resulted in a large reduction of hydrolytic activity on 3-glucosylated flavonoids. 28142197 0 71 theme active 84:89 arg1 mutants 96:102 active site mutants 84:102 active site mutants 84:102 Crystal structure of β-glucosidase 1A from Thermotoga neapolitana and comparison of active site mutants for hydrolysis of flavonoid glucosides. 28142197 0 72 theme mutants 96:102 arg1 comparison 70:79 comparison 70:79 comparison of active site mutants for hydrolysis of flavonoid glucosides 70:141 Crystal structure of β-glucosidase 1A from Thermotoga neapolitana and comparison of active site mutants for hydrolysis of flavonoid glucosides. 28142197 0 72 theme mutants 96:102 arg1 neapolitana 54:64 Thermotoga neapolitana 43:64 Thermotoga neapolitana 43:64 Crystal structure of β-glucosidase 1A from Thermotoga neapolitana and comparison of active site mutants for hydrolysis of flavonoid glucosides. 28142197 7 73 from N220 1371:1374 arg1 Substitution 1348:1359 Substitution 1348:1359 Substitution by Ser at N220 or N221 1348:1382 Substitution by Ser at N220 or N221 increased the catalytic efficiency on both pNPGlc and Q3. 28142197 0 74 from neapolitana 54:64 arg1 structure 8:16 Crystal structure 0:16 Crystal structure of β-glucosidase 1A from Thermotoga neapolitana and comparison of active site mutants for hydrolysis of flavonoid glucosides. 0:142 Crystal structure of β-glucosidase 1A from Thermotoga neapolitana and comparison of active site mutants for hydrolysis of flavonoid glucosides. 28142197 4 75 theme nucleophile 796:806 arg1 TnBgl1A-E349G 815:827 the nucleophile mutant TnBgl1A-E349G 792:827 the nucleophile mutant TnBgl1A-E349G 792:827 To further explore structure-function relationships, the crystal structure of the nucleophile mutant TnBgl1A-E349G was determined at 1.9 Å resolution, and docking studies of flavonoid substrates were made to reveal substrate interacting residues. 28142197 2 76 theme results 464:470 arg1 modification 434:445 modification 434:445 modification of glycosylation results in modulation of bioavailability 434:503 Enzymes with this specificity have potential in lignocellulose conversion (degrading cellobiose to glucose) and conversion of bioactive flavonoids (modification of glycosylation results in modulation of bioavailability). 28142197 4 77 theme TnBgl1A-E349G 815:827 arg1 structure 779:787 the crystal structure 767:787 the crystal structure of the nucleophile mutant TnBgl1A-E349G 767:827 To further explore structure-function relationships, the crystal structure of the nucleophile mutant TnBgl1A-E349G was determined at 1.9 Å resolution, and docking studies of flavonoid substrates were made to reveal substrate interacting residues. 28142197 5 78 theme amino 980:984 arg1 changes 991:997 single amino acid changes 973:997 single amino acid changes 973:997 A series of single amino acid changes were introduced in the aglycone binding region [N220(S/F), N221(S/F), F224(I), F310(L/E), and W322(A)] of the wild type. 28142197 13 79 dep © 2038:2038 arg1 Inc. 2064:2067 Inc. 2064:2067 Inc. 2064:2067 © 2016 Wiley Periodicals, Inc. 28142197 4 80 theme crystal 771:777 arg1 structure 779:787 the crystal structure 767:787 the crystal structure of the nucleophile mutant TnBgl1A-E349G 767:827 To further explore structure-function relationships, the crystal structure of the nucleophile mutant TnBgl1A-E349G was determined at 1.9 Å resolution, and docking studies of flavonoid substrates were made to reveal substrate interacting residues. 28142197 2 81 theme flavonoids 422:431 arg1 conversion 349:358 lignocellulose conversion 334:358 lignocellulose conversion (degrading cellobiose to glucose) 334:392 Enzymes with this specificity have potential in lignocellulose conversion (degrading cellobiose to glucose) and conversion of bioactive flavonoids (modification of glycosylation results in modulation of bioavailability). 28142197 2 81 theme flavonoids 422:431 arg1 conversion 398:407 conversion 398:407 conversion of bioactive flavonoids (modification of glycosylation results in modulation of bioavailability) 398:504 Enzymes with this specificity have potential in lignocellulose conversion (degrading cellobiose to glucose) and conversion of bioactive flavonoids (modification of glycosylation results in modulation of bioavailability). 28142197 0 82 theme β-glucosidase 21:33 arg1 1A 35:36 β-glucosidase 1A 21:36 β-glucosidase 1A 21:36 Crystal structure of β-glucosidase 1A from Thermotoga neapolitana and comparison of active site mutants for hydrolysis of flavonoid glucosides. 28142197 2 83 contain have 316:319 arg1 Enzymes 286:292 Enzymes 286:292 Enzymes with this specificity 286:314 Enzymes with this specificity have potential in lignocellulose conversion (degrading cellobiose to glucose) and conversion of bioactive flavonoids (modification of glycosylation results in modulation of bioavailability). 28142197 2 83 contain have 316:319 arg2 potential 321:329 potential 321:329 potential 321:329 Enzymes with this specificity have potential in lignocellulose conversion (degrading cellobiose to glucose) and conversion of bioactive flavonoids (modification of glycosylation results in modulation of bioavailability). 28142197 5 84 theme changes 991:997 arg1 series 963:968 A series 961:968 A series of single amino acid changes 961:997 A series of single amino acid changes were introduced in the aglycone binding region [N220(S/F), N221(S/F), F224(I), F310(L/E), and W322(A)] of the wild type. 28142197 11 85 theme TnBgl1A 1880:1886 arg1 region 1870:1875 the aglycone region 1857:1875 the aglycone region of TnBgl1A of importance for specificity on flavonoid-3-glucosides 1857:1942 This work pinpoints positions in the aglycone region of TnBgl1A of importance for specificity on flavonoid-3-glucosides, improving the molecular understanding of activity in GH1 enzymes. 28142197 5 86 theme type 1114:1117 arg1 S/F 1063:1065 S/F 1063:1065 S/F 1063:1065 A series of single amino acid changes were introduced in the aglycone binding region [N220(S/F), N221(S/F), F224(I), F310(L/E), and W322(A)] of the wild type. 28142197 5 86 theme type 1114:1117 arg1 W322 1093:1096 W322 1093:1096 W322(A)] of the wild type 1093:1117 A series of single amino acid changes were introduced in the aglycone binding region [N220(S/F), N221(S/F), F224(I), F310(L/E), and W322(A)] of the wild type. 28142197 5 86 theme type 1114:1117 arg1 F310 1078:1081 F310 1078:1081 F310(L/E) 1078:1086 A series of single amino acid changes were introduced in the aglycone binding region [N220(S/F), N221(S/F), F224(I), F310(L/E), and W322(A)] of the wild type. 28142197 5 86 theme type 1114:1117 arg1 S/F 1052:1054 S/F 1052:1054 S/F 1052:1054 A series of single amino acid changes were introduced in the aglycone binding region [N220(S/F), N221(S/F), F224(I), F310(L/E), and W322(A)] of the wild type. 28142197 5 86 theme type 1114:1117 arg1 L/E 1083:1085 L/E 1083:1085 L/E 1083:1085 A series of single amino acid changes were introduced in the aglycone binding region [N220(S/F), N221(S/F), F224(I), F310(L/E), and W322(A)] of the wild type. 28142197 5 86 theme type 1114:1117 arg1 A 1098:1098 A 1098:1098 A 1098:1098 A series of single amino acid changes were introduced in the aglycone binding region [N220(S/F), N221(S/F), F224(I), F310(L/E), and W322(A)] of the wild type. 28142197 5 86 theme type 1114:1117 arg1 F224 1069:1072 F224 1069:1072 F224(I) 1069:1075 A series of single amino acid changes were introduced in the aglycone binding region [N220(S/F), N221(S/F), F224(I), F310(L/E), and W322(A)] of the wild type. 28142197 5 86 theme type 1114:1117 arg1 N221 1058:1061 N221 1058:1061 N221(S/F) 1058:1066 A series of single amino acid changes were introduced in the aglycone binding region [N220(S/F), N221(S/F), F224(I), F310(L/E), and W322(A)] of the wild type. 28142197 5 86 theme type 1114:1117 arg1 I 1074:1074 I 1074:1074 I 1074:1074 A series of single amino acid changes were introduced in the aglycone binding region [N220(S/F), N221(S/F), F224(I), F310(L/E), and W322(A)] of the wild type. 28142197 5 86 theme type 1114:1117 arg1 region 1039:1044 the aglycone binding region [N220 1018:1050 the aglycone binding region [N220(S/F) 1018:1055 A series of single amino acid changes were introduced in the aglycone binding region [N220(S/F), N221(S/F), F224(I), F310(L/E), and W322(A)] of the wild type. 28142197 10 87 theme unfolding 1792:1800 arg1 temperature 1802:1812 an apparent unfolding temperature 1780:1812 an apparent unfolding temperature of 101°C 1780:1821 The mutations did not significantly affect thermal stability, and the variants kept an apparent unfolding temperature of 101°C. 28142197 2 88 theme glycosylation 450:462 arg1 results 464:470 glycosylation results 450:470 glycosylation results in modulation of bioavailability 450:503 Enzymes with this specificity have potential in lignocellulose conversion (degrading cellobiose to glucose) and conversion of bioactive flavonoids (modification of glycosylation results in modulation of bioavailability). 28142197 3 89 theme residue 700:706 arg1 mutagenesis 685:695 mutagenesis 685:695 mutagenesis of residue N220 685:711 Previous work has shown TnBgl1A to hydrolyse 3, 4' and 7 glucosylation in flavonoids, and although conversion of 3-glucosylated substrate to aglycone was low, it was improved by mutagenesis of residue N220. 28142197 3 90 theme 3 552:552 arg1 glucosylation 564:576 3, 4' and 7 glucosylation 552:576 3, 4' and 7 glucosylation in flavonoids 552:590 Previous work has shown TnBgl1A to hydrolyse 3, 4' and 7 glucosylation in flavonoids, and although conversion of 3-glucosylated substrate to aglycone was low, it was improved by mutagenesis of residue N220. 28142197 5 91 theme binding 1031:1037 arg1 region 1039:1044 the aglycone binding region [N220 1018:1050 the aglycone binding region [N220(S/F) 1018:1055 A series of single amino acid changes were introduced in the aglycone binding region [N220(S/F), N221(S/F), F224(I), F310(L/E), and W322(A)] of the wild type. 28142197 5 91 theme binding 1031:1037 arg1 S/F 1052:1054 S/F 1052:1054 S/F 1052:1054 A series of single amino acid changes were introduced in the aglycone binding region [N220(S/F), N221(S/F), F224(I), F310(L/E), and W322(A)] of the wild type. 28142197 2 92 from modification 434:445 arg1 modulation 475:484 modulation 475:484 modulation of bioavailability 475:503 Enzymes with this specificity have potential in lignocellulose conversion (degrading cellobiose to glucose) and conversion of bioactive flavonoids (modification of glycosylation results in modulation of bioavailability). 28142197 8 93 from activity 1572:1579 arg1 flavonoids 1599:1608 3-glucosylated flavonoids 1584:1608 3-glucosylated flavonoids 1584:1608 Residue W322 was proven important for substrate accomodation, as mutagenesis to W322A resulted in a large reduction of hydrolytic activity on 3-glucosylated flavonoids. 28142197 2 94 dep flavonoids 422:431 arg1 modification 434:445 modification 434:445 modification of glycosylation results in modulation of bioavailability 434:503 Enzymes with this specificity have potential in lignocellulose conversion (degrading cellobiose to glucose) and conversion of bioactive flavonoids (modification of glycosylation results in modulation of bioavailability). 28142197 11 95 from enzymes 2002:2008 arg1 understanding 1969:1981 the molecular understanding 1955:1981 the molecular understanding of activity in GH1 enzymes 1955:2008 This work pinpoints positions in the aglycone region of TnBgl1A of importance for specificity on flavonoid-3-glucosides, improving the molecular understanding of activity in GH1 enzymes. 28142197 1 96 theme glycosides/oligosaccharides 257:283 arg1 end 250:252 the nonreducing end 234:252 the nonreducing end of glycosides/oligosaccharides 234:283 The β-glucosidase TnBgl1A catalyses hydrolysis of O-linked terminal β-glycosidic bonds at the nonreducing end of glycosides/oligosaccharides. 28100784 6 0 theme mitochondrial 881:893 arg1 fragmentation 895:907 Drp1-dependent mitochondrial fragmentation 866:907 Drp1-dependent mitochondrial fragmentation 866:907 Using siRNA in HeLa cells, we found that reducing endogenous mOGT expression leads to alterations in mitochondrial structure and function, including Drp1-dependent mitochondrial fragmentation, reduction in mitochondrial membrane potential, and a significant loss of mitochondrial content in the absence of mitochondrial ROS. 28100784 9 1 theme isoforms 1405:1412 arg1 expression 1331:1340 reduced expression 1323:1340 reduced expression of both nucleocytoplasmic (ncOGT) and mitochondrial (mOGT) OGT isoforms 1323:1412 Conversely, reduced expression of both nucleocytoplasmic (ncOGT) and mitochondrial (mOGT) OGT isoforms is associated with increased mitochondrial respiration and elevated glycolysis, suggesting that ncOGT is a negative regulator of cellular bioenergetics. 28100784 12 2 theme cellular 2057:2064 arg1 bioenergetics 2066:2078 cellular bioenergetics 2057:2078 cellular bioenergetics 2057:2078 Our findings suggest that mOGT is catalytically active in vivo and supports mitochondrial structure, health, and survival, whereas ncOGT predominantly regulates cellular bioenergetics. 28100784 5 3 gly glycoproteins 569:581 arg1 glycoproteins 569:581 the candidate glycoproteins 555:581 the candidate glycoproteins identified (cytochrome oxidase 2 (COX2) and NADH:ubiquinone oxidoreductase core subunit 4 (MT-ND4)) 555:681 Notably, two of the candidate glycoproteins identified (cytochrome oxidase 2 (COX2) and NADH:ubiquinone oxidoreductase core subunit 4 (MT-ND4)) are encoded by mitochondrial DNA. 28100784 5 4 theme ubiquinone 632:641 arg1 oxidoreductase 643:656 ubiquinone oxidoreductase core subunit 4 (MT-ND4) 632:680 NADH:ubiquinone oxidoreductase core subunit 4 (MT-ND4) 627:680 Notably, two of the candidate glycoproteins identified (cytochrome oxidase 2 (COX2) and NADH:ubiquinone oxidoreductase core subunit 4 (MT-ND4)) are encoded by mitochondrial DNA. 28100784 7 5 theme compensatory 1078:1089 arg1 increase 1091:1098 a compensatory increase 1076:1098 a compensatory increase in oxidative phosphorylation per mitochondrion 1076:1145 These defects are associated with a compensatory increase in oxidative phosphorylation per mitochondrion. 28100784 2 6 theme single 272:277 arg1 gene 279:282 a single gene 270:282 a single gene that yields nucleocytosolic and mitochondrial isoforms 270:337 OGT is encoded by a single gene that yields nucleocytosolic and mitochondrial isoforms. 28100784 9 7 theme increased 1433:1441 arg1 respiration 1457:1467 increased mitochondrial respiration 1433:1467 increased mitochondrial respiration 1433:1467 Conversely, reduced expression of both nucleocytoplasmic (ncOGT) and mitochondrial (mOGT) OGT isoforms is associated with increased mitochondrial respiration and elevated glycolysis, suggesting that ncOGT is a negative regulator of cellular bioenergetics. 28100784 11 8 theme PPR-containing 1834:1847 arg1 protein 1849:1855 leucine-rich PPR-containing protein 1821:1855 leucine-rich PPR-containing protein 1821:1855 We identified four proteins implicated in mitochondrial biogenesis and metabolism regulation as candidate substrates of mOGT, including leucine-rich PPR-containing protein and mitochondrial aconitate hydratase. 28100784 6 9 theme HeLa 732:735 arg1 cells 737:741 HeLa cells 732:741 HeLa cells 732:741 Using siRNA in HeLa cells, we found that reducing endogenous mOGT expression leads to alterations in mitochondrial structure and function, including Drp1-dependent mitochondrial fragmentation, reduction in mitochondrial membrane potential, and a significant loss of mitochondrial content in the absence of mitochondrial ROS. 28100784 2 10 theme mitochondrial 316:328 arg1 isoforms 330:337 nucleocytosolic and mitochondrial isoforms 296:337 nucleocytosolic and mitochondrial isoforms 296:337 OGT is encoded by a single gene that yields nucleocytosolic and mitochondrial isoforms. 28100784 1 11 theme target 191:196 arg1 proteins 198:205 target proteins 191:205 target proteins 191:205 O-Linked N-acetylglucosamine transferase (OGT) catalyzes O-GlcNAcylation of target proteins and regulates numerous biological processes. 28100784 8 12 theme siRNA-mediated 1189:1202 arg1 knockdown 1204:1212 siRNA-mediated knockdown 1189:1212 siRNA-mediated knockdown of endogenous mOGT 1189:1231 mOGT is also critical for cell survival; siRNA-mediated knockdown of endogenous mOGT protected cells against toxicity mediated by rotenone, a complex I inhibitor. 28100784 2 13 theme nucleocytosolic 296:310 arg1 isoforms 330:337 nucleocytosolic and mitochondrial isoforms 296:337 nucleocytosolic and mitochondrial isoforms 296:337 OGT is encoded by a single gene that yields nucleocytosolic and mitochondrial isoforms. 28100784 9 14 theme elevated 1473:1480 arg1 glycolysis 1482:1491 elevated glycolysis 1473:1491 elevated glycolysis 1473:1491 Conversely, reduced expression of both nucleocytoplasmic (ncOGT) and mitochondrial (mOGT) OGT isoforms is associated with increased mitochondrial respiration and elevated glycolysis, suggesting that ncOGT is a negative regulator of cellular bioenergetics. 28100784 6 15 theme membrane 937:944 arg1 potential 946:954 mitochondrial membrane potential 923:954 mitochondrial membrane potential 923:954 Using siRNA in HeLa cells, we found that reducing endogenous mOGT expression leads to alterations in mitochondrial structure and function, including Drp1-dependent mitochondrial fragmentation, reduction in mitochondrial membrane potential, and a significant loss of mitochondrial content in the absence of mitochondrial ROS. 28100784 0 16 from Function 77:84 arg1 Cells 108:112 HeLa Cells 103:112 HeLa Cells 103:112 Mitochondrial O-GlcNAc Transferase (mOGT) Regulates Mitochondrial Structure, Function, and Survival in HeLa Cells. 28100784 11 17 theme aconitate 1875:1883 arg1 hydratase 1885:1893 mitochondrial aconitate hydratase 1861:1893 mitochondrial aconitate hydratase 1861:1893 We identified four proteins implicated in mitochondrial biogenesis and metabolism regulation as candidate substrates of mOGT, including leucine-rich PPR-containing protein and mitochondrial aconitate hydratase. 28100784 1 18 theme numerous 221:228 arg1 processes 241:249 numerous biological processes 221:249 numerous biological processes 221:249 O-Linked N-acetylglucosamine transferase (OGT) catalyzes O-GlcNAcylation of target proteins and regulates numerous biological processes. 28100784 8 19 theme mOGT 1228:1231 arg1 knockdown 1204:1212 siRNA-mediated knockdown 1189:1212 siRNA-mediated knockdown of endogenous mOGT 1189:1231 mOGT is also critical for cell survival; siRNA-mediated knockdown of endogenous mOGT protected cells against toxicity mediated by rotenone, a complex I inhibitor. 28100784 0 20 from Structure 66:74 arg1 Cells 108:112 HeLa Cells 103:112 HeLa Cells 103:112 Mitochondrial O-GlcNAc Transferase (mOGT) Regulates Mitochondrial Structure, Function, and Survival in HeLa Cells. 28100784 8 21 theme complex 1290:1296 arg1 inhibitor 1300:1308 a complex I inhibitor 1288:1308 a complex I inhibitor 1288:1308 mOGT is also critical for cell survival; siRNA-mediated knockdown of endogenous mOGT protected cells against toxicity mediated by rotenone, a complex I inhibitor. 28100784 8 21 theme complex 1290:1296 arg1 rotenone 1278:1285 rotenone 1278:1285 rotenone 1278:1285 mOGT is also critical for cell survival; siRNA-mediated knockdown of endogenous mOGT protected cells against toxicity mediated by rotenone, a complex I inhibitor. 28100784 5 22 theme core 658:661 arg1 subunit 663:669 core subunit 4 658:671 NADH:ubiquinone oxidoreductase core subunit 4 (MT-ND4) 627:680 Notably, two of the candidate glycoproteins identified (cytochrome oxidase 2 (COX2) and NADH:ubiquinone oxidoreductase core subunit 4 (MT-ND4)) are encoded by mitochondrial DNA. 28100784 5 22 theme core 658:661 arg1 MT-ND4 674:679 MT-ND4 674:679 MT-ND4 674:679 Notably, two of the candidate glycoproteins identified (cytochrome oxidase 2 (COX2) and NADH:ubiquinone oxidoreductase core subunit 4 (MT-ND4)) are encoded by mitochondrial DNA. 28100784 1 23 theme N-acetylglucosamine 124:142 arg1 OGT 157:159 OGT 157:159 OGT 157:159 O-Linked N-acetylglucosamine transferase (OGT) catalyzes O-GlcNAcylation of target proteins and regulates numerous biological processes. 28100784 1 23 theme N-acetylglucosamine 124:142 arg1 transferase 144:154 O-Linked N-acetylglucosamine transferase 115:154 O-Linked N-acetylglucosamine transferase (OGT) 115:160 O-Linked N-acetylglucosamine transferase (OGT) catalyzes O-GlcNAcylation of target proteins and regulates numerous biological processes. 28100784 5 24 dep NADH 627:630 arg1 oxidoreductase 643:656 ubiquinone oxidoreductase core subunit 4 (MT-ND4) 632:680 NADH:ubiquinone oxidoreductase core subunit 4 (MT-ND4) 627:680 Notably, two of the candidate glycoproteins identified (cytochrome oxidase 2 (COX2) and NADH:ubiquinone oxidoreductase core subunit 4 (MT-ND4)) are encoded by mitochondrial DNA. 28100784 9 25 theme negative 1521:1528 arg1 ncOGT 1510:1514 ncOGT 1510:1514 ncOGT 1510:1514 Conversely, reduced expression of both nucleocytoplasmic (ncOGT) and mitochondrial (mOGT) OGT isoforms is associated with increased mitochondrial respiration and elevated glycolysis, suggesting that ncOGT is a negative regulator of cellular bioenergetics. 28100784 9 25 theme negative 1521:1528 arg1 regulator 1530:1538 a negative regulator 1519:1538 a negative regulator of cellular bioenergetics 1519:1564 Conversely, reduced expression of both nucleocytoplasmic (ncOGT) and mitochondrial (mOGT) OGT isoforms is associated with increased mitochondrial respiration and elevated glycolysis, suggesting that ncOGT is a negative regulator of cellular bioenergetics. 28100784 6 26 theme mitochondrial 983:995 arg1 content 997:1003 mitochondrial content 983:1003 mitochondrial content 983:1003 Using siRNA in HeLa cells, we found that reducing endogenous mOGT expression leads to alterations in mitochondrial structure and function, including Drp1-dependent mitochondrial fragmentation, reduction in mitochondrial membrane potential, and a significant loss of mitochondrial content in the absence of mitochondrial ROS. 28100784 4 27 theme mitochondrial 487:499 arg1 glycoproteins 501:513 84 candidate mitochondrial glycoproteins 474:513 84 candidate mitochondrial glycoproteins 474:513 Using high throughput proteomics, we identified 84 candidate mitochondrial glycoproteins, of which 44 are novel. 28100784 11 28 theme mOGT 1805:1808 arg1 proteins 1704:1711 four proteins 1699:1711 four proteins implicated in mitochondrial biogenesis and metabolism regulation 1699:1776 We identified four proteins implicated in mitochondrial biogenesis and metabolism regulation as candidate substrates of mOGT, including leucine-rich PPR-containing protein and mitochondrial aconitate hydratase. 28100784 11 28 theme mOGT 1805:1808 arg1 protein 1849:1855 leucine-rich PPR-containing protein 1821:1855 leucine-rich PPR-containing protein 1821:1855 We identified four proteins implicated in mitochondrial biogenesis and metabolism regulation as candidate substrates of mOGT, including leucine-rich PPR-containing protein and mitochondrial aconitate hydratase. 28100784 11 28 theme mOGT 1805:1808 arg1 substrates 1791:1800 candidate substrates 1781:1800 candidate substrates 1781:1800 We identified four proteins implicated in mitochondrial biogenesis and metabolism regulation as candidate substrates of mOGT, including leucine-rich PPR-containing protein and mitochondrial aconitate hydratase. 28100784 11 28 theme mOGT 1805:1808 arg1 hydratase 1885:1893 mitochondrial aconitate hydratase 1861:1893 mitochondrial aconitate hydratase 1861:1893 We identified four proteins implicated in mitochondrial biogenesis and metabolism regulation as candidate substrates of mOGT, including leucine-rich PPR-containing protein and mitochondrial aconitate hydratase. 28100784 12 29 from vivo 1954:1957 arg1 active 1944:1949 active 1944:1949 active 1944:1949 Our findings suggest that mOGT is catalytically active in vivo and supports mitochondrial structure, health, and survival, whereas ncOGT predominantly regulates cellular bioenergetics. 28100784 5 30 theme cytochrome 595:604 arg1 COX2 617:620 COX2 617:620 COX2 617:620 Notably, two of the candidate glycoproteins identified (cytochrome oxidase 2 (COX2) and NADH:ubiquinone oxidoreductase core subunit 4 (MT-ND4)) are encoded by mitochondrial DNA. 28100784 5 30 theme cytochrome 595:604 arg1 oxidase 606:612 cytochrome oxidase 2 595:614 cytochrome oxidase 2 (COX2) 595:621 Notably, two of the candidate glycoproteins identified (cytochrome oxidase 2 (COX2) and NADH:ubiquinone oxidoreductase core subunit 4 (MT-ND4)) are encoded by mitochondrial DNA. 28100784 9 31 theme bioenergetics 1552:1564 arg1 ncOGT 1510:1514 ncOGT 1510:1514 ncOGT 1510:1514 Conversely, reduced expression of both nucleocytoplasmic (ncOGT) and mitochondrial (mOGT) OGT isoforms is associated with increased mitochondrial respiration and elevated glycolysis, suggesting that ncOGT is a negative regulator of cellular bioenergetics. 28100784 9 31 theme bioenergetics 1552:1564 arg1 regulator 1530:1538 a negative regulator 1519:1538 a negative regulator of cellular bioenergetics 1519:1564 Conversely, reduced expression of both nucleocytoplasmic (ncOGT) and mitochondrial (mOGT) OGT isoforms is associated with increased mitochondrial respiration and elevated glycolysis, suggesting that ncOGT is a negative regulator of cellular bioenergetics. 28100784 12 32 from active 1944:1949 arg1 vivo 1954:1957 vivo 1954:1957 vivo 1954:1957 Our findings suggest that mOGT is catalytically active in vivo and supports mitochondrial structure, health, and survival, whereas ncOGT predominantly regulates cellular bioenergetics. 28100784 5 33 dep oxidoreductase 643:656 arg1 subunit 663:669 core subunit 4 658:671 NADH:ubiquinone oxidoreductase core subunit 4 (MT-ND4) 627:680 Notably, two of the candidate glycoproteins identified (cytochrome oxidase 2 (COX2) and NADH:ubiquinone oxidoreductase core subunit 4 (MT-ND4)) are encoded by mitochondrial DNA. 28100784 5 33 dep oxidoreductase 643:656 arg1 MT-ND4 674:679 MT-ND4 674:679 MT-ND4 674:679 Notably, two of the candidate glycoproteins identified (cytochrome oxidase 2 (COX2) and NADH:ubiquinone oxidoreductase core subunit 4 (MT-ND4)) are encoded by mitochondrial DNA. 28100784 5 34 theme mitochondrial 698:710 arg1 DNA 712:714 mitochondrial DNA 698:714 mitochondrial DNA 698:714 Notably, two of the candidate glycoproteins identified (cytochrome oxidase 2 (COX2) and NADH:ubiquinone oxidoreductase core subunit 4 (MT-ND4)) are encoded by mitochondrial DNA. 28100784 10 35 theme restricted 1644:1653 arg1 set 1655:1657 a restricted set 1642:1657 a restricted set of mitochondrial targets 1642:1682 Last, we determined that mOGT is probably involved in the glycosylation of a restricted set of mitochondrial targets. 28100784 10 35 theme restricted 1644:1653 arg1 targets 1676:1682 mitochondrial targets 1662:1682 mitochondrial targets 1662:1682 Last, we determined that mOGT is probably involved in the glycosylation of a restricted set of mitochondrial targets. 28100784 0 36 theme Mitochondrial 0:12 arg1 Transferase 23:33 Mitochondrial O-GlcNAc Transferase 0:33 Mitochondrial O-GlcNAc Transferase (mOGT) 0:40 Mitochondrial O-GlcNAc Transferase (mOGT) Regulates Mitochondrial Structure, Function, and Survival in HeLa Cells. 28100784 0 36 theme Mitochondrial 0:12 arg1 mOGT 36:39 mOGT 36:39 mOGT 36:39 Mitochondrial O-GlcNAc Transferase (mOGT) Regulates Mitochondrial Structure, Function, and Survival in HeLa Cells. 28100784 5 37 theme candidate 559:567 arg1 glycoproteins 569:581 the candidate glycoproteins 555:581 the candidate glycoproteins identified (cytochrome oxidase 2 (COX2) and NADH:ubiquinone oxidoreductase core subunit 4 (MT-ND4)) 555:681 Notably, two of the candidate glycoproteins identified (cytochrome oxidase 2 (COX2) and NADH:ubiquinone oxidoreductase core subunit 4 (MT-ND4)) are encoded by mitochondrial DNA. 28100784 3 38 theme mitochondrial 365:377 arg1 isoform 379:385 the mitochondrial isoform 361:385 the mitochondrial isoform of OGT (mOGT) 361:399 To date, the role of the mitochondrial isoform of OGT (mOGT) remains largely unknown. 28100784 6 39 theme mitochondrial 818:830 arg1 structure 832:840 mitochondrial structure 818:840 mitochondrial structure 818:840 Using siRNA in HeLa cells, we found that reducing endogenous mOGT expression leads to alterations in mitochondrial structure and function, including Drp1-dependent mitochondrial fragmentation, reduction in mitochondrial membrane potential, and a significant loss of mitochondrial content in the absence of mitochondrial ROS. 28100784 6 40 theme mitochondrial 1023:1035 arg1 ROS 1037:1039 mitochondrial ROS 1023:1039 mitochondrial ROS 1023:1039 Using siRNA in HeLa cells, we found that reducing endogenous mOGT expression leads to alterations in mitochondrial structure and function, including Drp1-dependent mitochondrial fragmentation, reduction in mitochondrial membrane potential, and a significant loss of mitochondrial content in the absence of mitochondrial ROS. 28100784 10 41 theme targets 1676:1682 arg1 set 1655:1657 a restricted set 1642:1657 a restricted set of mitochondrial targets 1642:1682 Last, we determined that mOGT is probably involved in the glycosylation of a restricted set of mitochondrial targets. 28100784 10 41 theme targets 1676:1682 arg1 targets 1676:1682 mitochondrial targets 1662:1682 mitochondrial targets 1662:1682 Last, we determined that mOGT is probably involved in the glycosylation of a restricted set of mitochondrial targets. 28100784 6 42 from reduction 910:918 arg1 potential 946:954 mitochondrial membrane potential 923:954 mitochondrial membrane potential 923:954 Using siRNA in HeLa cells, we found that reducing endogenous mOGT expression leads to alterations in mitochondrial structure and function, including Drp1-dependent mitochondrial fragmentation, reduction in mitochondrial membrane potential, and a significant loss of mitochondrial content in the absence of mitochondrial ROS. 28100784 9 43 theme mitochondrial 1380:1392 arg1 isoforms 1405:1412 both nucleocytoplasmic (ncOGT) and mitochondrial (mOGT) OGT isoforms 1345:1412 both nucleocytoplasmic (ncOGT) and mitochondrial (mOGT) OGT isoforms 1345:1412 Conversely, reduced expression of both nucleocytoplasmic (ncOGT) and mitochondrial (mOGT) OGT isoforms is associated with increased mitochondrial respiration and elevated glycolysis, suggesting that ncOGT is a negative regulator of cellular bioenergetics. 28100784 6 44 theme mOGT 778:781 arg1 expression 783:792 endogenous mOGT expression 767:792 endogenous mOGT expression 767:792 Using siRNA in HeLa cells, we found that reducing endogenous mOGT expression leads to alterations in mitochondrial structure and function, including Drp1-dependent mitochondrial fragmentation, reduction in mitochondrial membrane potential, and a significant loss of mitochondrial content in the absence of mitochondrial ROS. 28100784 11 45 theme mitochondrial 1727:1739 arg1 biogenesis 1741:1750 biogenesis 1741:1750 biogenesis 1741:1750 We identified four proteins implicated in mitochondrial biogenesis and metabolism regulation as candidate substrates of mOGT, including leucine-rich PPR-containing protein and mitochondrial aconitate hydratase. 28100784 6 46 from fragmentation 895:907 arg1 potential 946:954 mitochondrial membrane potential 923:954 mitochondrial membrane potential 923:954 Using siRNA in HeLa cells, we found that reducing endogenous mOGT expression leads to alterations in mitochondrial structure and function, including Drp1-dependent mitochondrial fragmentation, reduction in mitochondrial membrane potential, and a significant loss of mitochondrial content in the absence of mitochondrial ROS. 28100784 7 47 theme oxidative 1103:1111 arg1 phosphorylation 1113:1127 oxidative phosphorylation 1103:1127 oxidative phosphorylation per mitochondrion 1103:1145 These defects are associated with a compensatory increase in oxidative phosphorylation per mitochondrion. 28100784 9 48 theme OGT 1401:1403 arg1 isoforms 1405:1412 both nucleocytoplasmic (ncOGT) and mitochondrial (mOGT) OGT isoforms 1345:1412 both nucleocytoplasmic (ncOGT) and mitochondrial (mOGT) OGT isoforms 1345:1412 Conversely, reduced expression of both nucleocytoplasmic (ncOGT) and mitochondrial (mOGT) OGT isoforms is associated with increased mitochondrial respiration and elevated glycolysis, suggesting that ncOGT is a negative regulator of cellular bioenergetics. 28100784 9 49 dep nucleocytoplasmic 1350:1366 arg1 mOGT 1395:1398 mOGT 1395:1398 mOGT 1395:1398 Conversely, reduced expression of both nucleocytoplasmic (ncOGT) and mitochondrial (mOGT) OGT isoforms is associated with increased mitochondrial respiration and elevated glycolysis, suggesting that ncOGT is a negative regulator of cellular bioenergetics. 28100784 9 49 dep nucleocytoplasmic 1350:1366 arg1 ncOGT 1369:1373 ncOGT 1369:1373 ncOGT 1369:1373 Conversely, reduced expression of both nucleocytoplasmic (ncOGT) and mitochondrial (mOGT) OGT isoforms is associated with increased mitochondrial respiration and elevated glycolysis, suggesting that ncOGT is a negative regulator of cellular bioenergetics. 28100784 6 50 theme Drp1-dependent 866:879 arg1 fragmentation 895:907 Drp1-dependent mitochondrial fragmentation 866:907 Drp1-dependent mitochondrial fragmentation 866:907 Using siRNA in HeLa cells, we found that reducing endogenous mOGT expression leads to alterations in mitochondrial structure and function, including Drp1-dependent mitochondrial fragmentation, reduction in mitochondrial membrane potential, and a significant loss of mitochondrial content in the absence of mitochondrial ROS. 28100784 11 51 dep biogenesis 1741:1750 arg1 regulation 1767:1776 regulation 1767:1776 regulation 1767:1776 We identified four proteins implicated in mitochondrial biogenesis and metabolism regulation as candidate substrates of mOGT, including leucine-rich PPR-containing protein and mitochondrial aconitate hydratase. 28100784 4 52 gly glycoproteins 501:513 arg1 glycoproteins 501:513 84 candidate mitochondrial glycoproteins 474:513 84 candidate mitochondrial glycoproteins 474:513 Using high throughput proteomics, we identified 84 candidate mitochondrial glycoproteins, of which 44 are novel. 28100784 6 53 from alterations 803:813 arg1 function 846:853 function 846:853 function 846:853 Using siRNA in HeLa cells, we found that reducing endogenous mOGT expression leads to alterations in mitochondrial structure and function, including Drp1-dependent mitochondrial fragmentation, reduction in mitochondrial membrane potential, and a significant loss of mitochondrial content in the absence of mitochondrial ROS. 28100784 6 53 from alterations 803:813 arg1 structure 832:840 mitochondrial structure 818:840 mitochondrial structure 818:840 Using siRNA in HeLa cells, we found that reducing endogenous mOGT expression leads to alterations in mitochondrial structure and function, including Drp1-dependent mitochondrial fragmentation, reduction in mitochondrial membrane potential, and a significant loss of mitochondrial content in the absence of mitochondrial ROS. 28100784 9 54 theme mitochondrial 1443:1455 arg1 respiration 1457:1467 increased mitochondrial respiration 1433:1467 increased mitochondrial respiration 1433:1467 Conversely, reduced expression of both nucleocytoplasmic (ncOGT) and mitochondrial (mOGT) OGT isoforms is associated with increased mitochondrial respiration and elevated glycolysis, suggesting that ncOGT is a negative regulator of cellular bioenergetics. 28100784 8 55 theme cell 1174:1177 arg1 survival 1179:1186 cell survival 1174:1186 cell survival 1174:1186 mOGT is also critical for cell survival; siRNA-mediated knockdown of endogenous mOGT protected cells against toxicity mediated by rotenone, a complex I inhibitor. 28100784 1 56 theme proteins 198:205 arg1 O-GlcNAcylation 172:186 O-GlcNAcylation 172:186 O-GlcNAcylation of target proteins 172:205 O-Linked N-acetylglucosamine transferase (OGT) catalyzes O-GlcNAcylation of target proteins and regulates numerous biological processes. 28100784 4 57 theme throughput 437:446 arg1 proteomics 448:457 high throughput proteomics 432:457 high throughput proteomics 432:457 Using high throughput proteomics, we identified 84 candidate mitochondrial glycoproteins, of which 44 are novel. 28100784 11 58 theme leucine-rich 1821:1832 arg1 protein 1849:1855 leucine-rich PPR-containing protein 1821:1855 leucine-rich PPR-containing protein 1821:1855 We identified four proteins implicated in mitochondrial biogenesis and metabolism regulation as candidate substrates of mOGT, including leucine-rich PPR-containing protein and mitochondrial aconitate hydratase. 28100784 6 59 theme mitochondrial 923:935 arg1 potential 946:954 mitochondrial membrane potential 923:954 mitochondrial membrane potential 923:954 Using siRNA in HeLa cells, we found that reducing endogenous mOGT expression leads to alterations in mitochondrial structure and function, including Drp1-dependent mitochondrial fragmentation, reduction in mitochondrial membrane potential, and a significant loss of mitochondrial content in the absence of mitochondrial ROS. 28100784 8 60 theme endogenous 1217:1226 arg1 mOGT 1228:1231 endogenous mOGT 1217:1231 endogenous mOGT 1217:1231 mOGT is also critical for cell survival; siRNA-mediated knockdown of endogenous mOGT protected cells against toxicity mediated by rotenone, a complex I inhibitor. 28100784 11 61 theme mitochondrial 1861:1873 arg1 hydratase 1885:1893 mitochondrial aconitate hydratase 1861:1893 mitochondrial aconitate hydratase 1861:1893 We identified four proteins implicated in mitochondrial biogenesis and metabolism regulation as candidate substrates of mOGT, including leucine-rich PPR-containing protein and mitochondrial aconitate hydratase. 28100784 1 62 theme O-Linked 115:122 arg1 OGT 157:159 OGT 157:159 OGT 157:159 O-Linked N-acetylglucosamine transferase (OGT) catalyzes O-GlcNAcylation of target proteins and regulates numerous biological processes. 28100784 1 62 theme O-Linked 115:122 arg1 transferase 144:154 O-Linked N-acetylglucosamine transferase 115:154 O-Linked N-acetylglucosamine transferase (OGT) 115:160 O-Linked N-acetylglucosamine transferase (OGT) catalyzes O-GlcNAcylation of target proteins and regulates numerous biological processes. 28100784 0 63 from Survival 91:98 arg1 Cells 108:112 HeLa Cells 103:112 HeLa Cells 103:112 Mitochondrial O-GlcNAc Transferase (mOGT) Regulates Mitochondrial Structure, Function, and Survival in HeLa Cells. 28100784 8 64 theme I 1298:1298 arg1 inhibitor 1300:1308 a complex I inhibitor 1288:1308 a complex I inhibitor 1288:1308 mOGT is also critical for cell survival; siRNA-mediated knockdown of endogenous mOGT protected cells against toxicity mediated by rotenone, a complex I inhibitor. 28100784 8 64 theme I 1298:1298 arg1 rotenone 1278:1285 rotenone 1278:1285 rotenone 1278:1285 mOGT is also critical for cell survival; siRNA-mediated knockdown of endogenous mOGT protected cells against toxicity mediated by rotenone, a complex I inhibitor. 28100784 11 65 theme candidate 1781:1789 arg1 proteins 1704:1711 four proteins 1699:1711 four proteins implicated in mitochondrial biogenesis and metabolism regulation 1699:1776 We identified four proteins implicated in mitochondrial biogenesis and metabolism regulation as candidate substrates of mOGT, including leucine-rich PPR-containing protein and mitochondrial aconitate hydratase. 28100784 11 65 theme candidate 1781:1789 arg1 protein 1849:1855 leucine-rich PPR-containing protein 1821:1855 leucine-rich PPR-containing protein 1821:1855 We identified four proteins implicated in mitochondrial biogenesis and metabolism regulation as candidate substrates of mOGT, including leucine-rich PPR-containing protein and mitochondrial aconitate hydratase. 28100784 11 65 theme candidate 1781:1789 arg1 substrates 1791:1800 candidate substrates 1781:1800 candidate substrates 1781:1800 We identified four proteins implicated in mitochondrial biogenesis and metabolism regulation as candidate substrates of mOGT, including leucine-rich PPR-containing protein and mitochondrial aconitate hydratase. 28100784 11 65 theme candidate 1781:1789 arg1 hydratase 1885:1893 mitochondrial aconitate hydratase 1861:1893 mitochondrial aconitate hydratase 1861:1893 We identified four proteins implicated in mitochondrial biogenesis and metabolism regulation as candidate substrates of mOGT, including leucine-rich PPR-containing protein and mitochondrial aconitate hydratase. 28100784 6 66 theme content 997:1003 arg1 loss 975:978 a significant loss 961:978 a significant loss of mitochondrial content 961:1003 Using siRNA in HeLa cells, we found that reducing endogenous mOGT expression leads to alterations in mitochondrial structure and function, including Drp1-dependent mitochondrial fragmentation, reduction in mitochondrial membrane potential, and a significant loss of mitochondrial content in the absence of mitochondrial ROS. 28100784 6 66 theme content 997:1003 arg1 reduction 910:918 reduction 910:918 reduction in mitochondrial membrane potential 910:954 Using siRNA in HeLa cells, we found that reducing endogenous mOGT expression leads to alterations in mitochondrial structure and function, including Drp1-dependent mitochondrial fragmentation, reduction in mitochondrial membrane potential, and a significant loss of mitochondrial content in the absence of mitochondrial ROS. 28100784 6 66 theme content 997:1003 arg1 fragmentation 895:907 Drp1-dependent mitochondrial fragmentation 866:907 Drp1-dependent mitochondrial fragmentation 866:907 Using siRNA in HeLa cells, we found that reducing endogenous mOGT expression leads to alterations in mitochondrial structure and function, including Drp1-dependent mitochondrial fragmentation, reduction in mitochondrial membrane potential, and a significant loss of mitochondrial content in the absence of mitochondrial ROS. 28100784 4 67 theme glycoproteins 501:513 arg1 novel 532:536 novel 532:536 novel 532:536 Using high throughput proteomics, we identified 84 candidate mitochondrial glycoproteins, of which 44 are novel. 28100784 1 68 theme biological 230:239 arg1 processes 241:249 numerous biological processes 221:249 numerous biological processes 221:249 O-Linked N-acetylglucosamine transferase (OGT) catalyzes O-GlcNAcylation of target proteins and regulates numerous biological processes. 28100784 12 69 theme mitochondrial 1972:1984 arg1 structure 1986:1994 mitochondrial structure 1972:1994 mitochondrial structure 1972:1994 Our findings suggest that mOGT is catalytically active in vivo and supports mitochondrial structure, health, and survival, whereas ncOGT predominantly regulates cellular bioenergetics. 28100784 10 70 gly glycosylation 1625:1637 arg1 set 1655:1657 a restricted set 1642:1657 a restricted set of mitochondrial targets 1642:1682 Last, we determined that mOGT is probably involved in the glycosylation of a restricted set of mitochondrial targets. 28100784 10 70 gly glycosylation 1625:1637 arg1 targets 1676:1682 mitochondrial targets 1662:1682 mitochondrial targets 1662:1682 Last, we determined that mOGT is probably involved in the glycosylation of a restricted set of mitochondrial targets. 28100784 9 71 theme cellular 1543:1550 arg1 bioenergetics 1552:1564 cellular bioenergetics 1543:1564 cellular bioenergetics 1543:1564 Conversely, reduced expression of both nucleocytoplasmic (ncOGT) and mitochondrial (mOGT) OGT isoforms is associated with increased mitochondrial respiration and elevated glycolysis, suggesting that ncOGT is a negative regulator of cellular bioenergetics. 28100784 6 72 theme significant 963:973 arg1 loss 975:978 a significant loss 961:978 a significant loss of mitochondrial content 961:1003 Using siRNA in HeLa cells, we found that reducing endogenous mOGT expression leads to alterations in mitochondrial structure and function, including Drp1-dependent mitochondrial fragmentation, reduction in mitochondrial membrane potential, and a significant loss of mitochondrial content in the absence of mitochondrial ROS. 28100784 0 73 theme HeLa 103:106 arg1 Cells 108:112 HeLa Cells 103:112 HeLa Cells 103:112 Mitochondrial O-GlcNAc Transferase (mOGT) Regulates Mitochondrial Structure, Function, and Survival in HeLa Cells. 28100784 4 74 theme candidate 477:485 arg1 glycoproteins 501:513 84 candidate mitochondrial glycoproteins 474:513 84 candidate mitochondrial glycoproteins 474:513 Using high throughput proteomics, we identified 84 candidate mitochondrial glycoproteins, of which 44 are novel. 28100784 10 75 theme set 1655:1657 arg1 glycosylation 1625:1637 the glycosylation 1621:1637 the glycosylation of a restricted set of mitochondrial targets 1621:1682 Last, we determined that mOGT is probably involved in the glycosylation of a restricted set of mitochondrial targets. 28100784 0 76 theme O-GlcNAc 14:21 arg1 Transferase 23:33 Mitochondrial O-GlcNAc Transferase 0:33 Mitochondrial O-GlcNAc Transferase (mOGT) 0:40 Mitochondrial O-GlcNAc Transferase (mOGT) Regulates Mitochondrial Structure, Function, and Survival in HeLa Cells. 28100784 0 76 theme O-GlcNAc 14:21 arg1 mOGT 36:39 mOGT 36:39 mOGT 36:39 Mitochondrial O-GlcNAc Transferase (mOGT) Regulates Mitochondrial Structure, Function, and Survival in HeLa Cells. 28100784 9 77 theme reduced 1323:1329 arg1 expression 1331:1340 reduced expression 1323:1340 reduced expression of both nucleocytoplasmic (ncOGT) and mitochondrial (mOGT) OGT isoforms 1323:1412 Conversely, reduced expression of both nucleocytoplasmic (ncOGT) and mitochondrial (mOGT) OGT isoforms is associated with increased mitochondrial respiration and elevated glycolysis, suggesting that ncOGT is a negative regulator of cellular bioenergetics. 28100784 3 78 theme OGT 390:392 arg1 isoform 379:385 the mitochondrial isoform 361:385 the mitochondrial isoform of OGT (mOGT) 361:399 To date, the role of the mitochondrial isoform of OGT (mOGT) remains largely unknown. 28100784 6 79 from loss 975:978 arg1 potential 946:954 mitochondrial membrane potential 923:954 mitochondrial membrane potential 923:954 Using siRNA in HeLa cells, we found that reducing endogenous mOGT expression leads to alterations in mitochondrial structure and function, including Drp1-dependent mitochondrial fragmentation, reduction in mitochondrial membrane potential, and a significant loss of mitochondrial content in the absence of mitochondrial ROS. 28100784 4 80 theme high 432:435 arg1 proteomics 448:457 high throughput proteomics 432:457 high throughput proteomics 432:457 Using high throughput proteomics, we identified 84 candidate mitochondrial glycoproteins, of which 44 are novel. 28100784 5 81 theme glycoproteins 569:581 arg1 glycoproteins 569:581 the candidate glycoproteins 555:581 the candidate glycoproteins identified (cytochrome oxidase 2 (COX2) and NADH:ubiquinone oxidoreductase core subunit 4 (MT-ND4)) 555:681 Notably, two of the candidate glycoproteins identified (cytochrome oxidase 2 (COX2) and NADH:ubiquinone oxidoreductase core subunit 4 (MT-ND4)) are encoded by mitochondrial DNA. 28100784 5 81 theme glycoproteins 569:581 arg1 two 548:550 two 548:550 two 548:550 Notably, two of the candidate glycoproteins identified (cytochrome oxidase 2 (COX2) and NADH:ubiquinone oxidoreductase core subunit 4 (MT-ND4)) are encoded by mitochondrial DNA. 28100784 6 82 theme ROS 1037:1039 arg1 absence 1012:1018 the absence 1008:1018 the absence of mitochondrial ROS 1008:1039 Using siRNA in HeLa cells, we found that reducing endogenous mOGT expression leads to alterations in mitochondrial structure and function, including Drp1-dependent mitochondrial fragmentation, reduction in mitochondrial membrane potential, and a significant loss of mitochondrial content in the absence of mitochondrial ROS. 28100784 3 83 theme isoform 379:385 arg1 role 353:356 the role 349:356 the role of the mitochondrial isoform of OGT (mOGT) 349:399 To date, the role of the mitochondrial isoform of OGT (mOGT) remains largely unknown. 28100784 9 84 theme nucleocytoplasmic 1350:1366 arg1 isoforms 1405:1412 both nucleocytoplasmic (ncOGT) and mitochondrial (mOGT) OGT isoforms 1345:1412 both nucleocytoplasmic (ncOGT) and mitochondrial (mOGT) OGT isoforms 1345:1412 Conversely, reduced expression of both nucleocytoplasmic (ncOGT) and mitochondrial (mOGT) OGT isoforms is associated with increased mitochondrial respiration and elevated glycolysis, suggesting that ncOGT is a negative regulator of cellular bioenergetics. 28100784 7 85 from increase 1091:1098 arg1 phosphorylation 1113:1127 oxidative phosphorylation 1103:1127 oxidative phosphorylation per mitochondrion 1103:1145 These defects are associated with a compensatory increase in oxidative phosphorylation per mitochondrion. 28100784 10 86 theme mitochondrial 1662:1674 arg1 targets 1676:1682 mitochondrial targets 1662:1682 mitochondrial targets 1662:1682 Last, we determined that mOGT is probably involved in the glycosylation of a restricted set of mitochondrial targets. 28100784 0 87 theme Mitochondrial 52:64 arg1 Structure 66:74 Mitochondrial Structure 52:74 Mitochondrial Structure 52:74 Mitochondrial O-GlcNAc Transferase (mOGT) Regulates Mitochondrial Structure, Function, and Survival in HeLa Cells. 28100784 6 88 theme endogenous 767:776 arg1 expression 783:792 endogenous mOGT expression 767:792 endogenous mOGT expression 767:792 Using siRNA in HeLa cells, we found that reducing endogenous mOGT expression leads to alterations in mitochondrial structure and function, including Drp1-dependent mitochondrial fragmentation, reduction in mitochondrial membrane potential, and a significant loss of mitochondrial content in the absence of mitochondrial ROS. 25453190 0 0 from modification 17:28 arg1 myoblasts 39:47 C2C12 myoblasts 33:47 C2C12 myoblasts exposed to oxidative stress 33:75 O-GlcNAc protein modification in C2C12 myoblasts exposed to oxidative stress indicates parallels with endogenous antioxidant defense. 25453190 4 1 theme 24 866:867 arg1 h 869:869 h 869:869 h 869:869 C2C12 myoblasts were subjected to 24 h incubation with different reagents, including hydrogen peroxide, diethyl maleate, high glucose, and glucosamine, and the inhibitors of O-GlcNAc cycling enzymes. 25453190 2 2 theme muscle 386:391 arg1 cells 393:397 skeletal muscle cells 377:397 skeletal muscle cells exposed to oxidative stress and the crosstalk with endogenous antioxidant system 377:478 Here we investigated protein O-GlcNAcylation in skeletal muscle cells exposed to oxidative stress and the crosstalk with endogenous antioxidant system. 25453190 6 3 from level 1188:1192 arg1 changes 1168:1174 Significant changes 1156:1174 Significant changes at the mRNA level 1156:1192 Significant changes at the mRNA level were observed with concomitant upregulation of the genes for O-GlcNAc enzymes and stress-related proteins with oxidizing agents and downregulation of these genes with agents promoting O-GlcNAcylation. 25453190 1 4 theme stress 268:273 arg1 response 275:282 the stress response 264:282 the stress response 264:282 A growing body of evidence demonstrates the involvement of protein modification with O-linked β-N-acetylglucosamine (O-GlcNAc) in the stress response and its beneficial effects on cell survival. 25453190 3 5 theme protein 717:723 arg1 enzymes 514:520 antioxidant enzymes 502:520 antioxidant enzymes superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPX1) 502:603 The study focused on antioxidant enzymes superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPX1), and transcriptional regulators proliferator-activated receptor gamma coactivator 1-α (PGC-1α) and forkhead box protein O1 (FOXO1), which play important roles in oxidative stress response and are known to be O-GlcNAc-modified. 25453190 3 5 theme protein 717:723 arg1 FOXO1 729:733 FOXO1 729:733 FOXO1 729:733 The study focused on antioxidant enzymes superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPX1), and transcriptional regulators proliferator-activated receptor gamma coactivator 1-α (PGC-1α) and forkhead box protein O1 (FOXO1), which play important roles in oxidative stress response and are known to be O-GlcNAc-modified. 25453190 3 5 theme protein 717:723 arg1 O1 725:726 forkhead box protein O1 704:726 forkhead box protein O1 (FOXO1) 704:734 The study focused on antioxidant enzymes superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPX1), and transcriptional regulators proliferator-activated receptor gamma coactivator 1-α (PGC-1α) and forkhead box protein O1 (FOXO1), which play important roles in oxidative stress response and are known to be O-GlcNAc-modified. 25453190 0 6 with parallels 87:95 arg1 defense 125:131 endogenous antioxidant defense 102:131 endogenous antioxidant defense 102:131 O-GlcNAc protein modification in C2C12 myoblasts exposed to oxidative stress indicates parallels with endogenous antioxidant defense. 25453190 2 7 theme skeletal 377:384 arg1 cells 393:397 skeletal muscle cells 377:397 skeletal muscle cells exposed to oxidative stress and the crosstalk with endogenous antioxidant system 377:478 Here we investigated protein O-GlcNAcylation in skeletal muscle cells exposed to oxidative stress and the crosstalk with endogenous antioxidant system. 25453190 6 8 with enzymes 1264:1270 arg1 agents 1315:1320 oxidizing agents 1305:1320 oxidizing agents 1305:1320 Significant changes at the mRNA level were observed with concomitant upregulation of the genes for O-GlcNAc enzymes and stress-related proteins with oxidizing agents and downregulation of these genes with agents promoting O-GlcNAcylation. 25453190 0 9 theme endogenous 102:111 arg1 defense 125:131 endogenous antioxidant defense 102:131 endogenous antioxidant defense 102:131 O-GlcNAc protein modification in C2C12 myoblasts exposed to oxidative stress indicates parallels with endogenous antioxidant defense. 25453190 2 10 with stress 420:425 arg1 system 473:478 endogenous antioxidant system 450:478 endogenous antioxidant system 450:478 Here we investigated protein O-GlcNAcylation in skeletal muscle cells exposed to oxidative stress and the crosstalk with endogenous antioxidant system. 25453190 1 11 from survival 319:326 arg1 involvement 178:188 the involvement 174:188 the involvement of protein modification with O-linked β-N-acetylglucosamine (O-GlcNAc) in the stress response and its beneficial effects on cell survival 174:326 A growing body of evidence demonstrates the involvement of protein modification with O-linked β-N-acetylglucosamine (O-GlcNAc) in the stress response and its beneficial effects on cell survival. 25453190 3 12 dep enzymes 514:520 arg1 GPX1 599:602 GPX1 599:602 GPX1 599:602 The study focused on antioxidant enzymes superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPX1), and transcriptional regulators proliferator-activated receptor gamma coactivator 1-α (PGC-1α) and forkhead box protein O1 (FOXO1), which play important roles in oxidative stress response and are known to be O-GlcNAc-modified. 25453190 3 12 dep enzymes 514:520 arg1 SOD2 546:549 SOD2 546:549 SOD2 546:549 The study focused on antioxidant enzymes superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPX1), and transcriptional regulators proliferator-activated receptor gamma coactivator 1-α (PGC-1α) and forkhead box protein O1 (FOXO1), which play important roles in oxidative stress response and are known to be O-GlcNAc-modified. 25453190 3 12 dep enzymes 514:520 arg1 FOXO1 729:733 FOXO1 729:733 FOXO1 729:733 The study focused on antioxidant enzymes superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPX1), and transcriptional regulators proliferator-activated receptor gamma coactivator 1-α (PGC-1α) and forkhead box protein O1 (FOXO1), which play important roles in oxidative stress response and are known to be O-GlcNAc-modified. 25453190 3 12 dep enzymes 514:520 arg1 enzymes 514:520 antioxidant enzymes 502:520 antioxidant enzymes superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPX1) 502:603 The study focused on antioxidant enzymes superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPX1), and transcriptional regulators proliferator-activated receptor gamma coactivator 1-α (PGC-1α) and forkhead box protein O1 (FOXO1), which play important roles in oxidative stress response and are known to be O-GlcNAc-modified. 25453190 3 12 dep enzymes 514:520 arg1 coactivator 675:685 proliferator-activated receptor gamma coactivator 1-α (PGC-1α) 637:698 proliferator-activated receptor gamma coactivator 1-α (PGC-1α) 637:698 The study focused on antioxidant enzymes superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPX1), and transcriptional regulators proliferator-activated receptor gamma coactivator 1-α (PGC-1α) and forkhead box protein O1 (FOXO1), which play important roles in oxidative stress response and are known to be O-GlcNAc-modified. 25453190 3 12 dep enzymes 514:520 arg1 peroxidase 585:594 glutathione peroxidase 1 573:596 glutathione peroxidase 1 (GPX1) 573:603 The study focused on antioxidant enzymes superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPX1), and transcriptional regulators proliferator-activated receptor gamma coactivator 1-α (PGC-1α) and forkhead box protein O1 (FOXO1), which play important roles in oxidative stress response and are known to be O-GlcNAc-modified. 25453190 3 12 dep enzymes 514:520 arg1 dismutase 533:541 superoxide dismutase 2 522:543 superoxide dismutase 2 (SOD2) 522:550 The study focused on antioxidant enzymes superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPX1), and transcriptional regulators proliferator-activated receptor gamma coactivator 1-α (PGC-1α) and forkhead box protein O1 (FOXO1), which play important roles in oxidative stress response and are known to be O-GlcNAc-modified. 25453190 3 12 dep enzymes 514:520 arg1 catalase 553:560 catalase 553:560 catalase (CAT) 553:566 The study focused on antioxidant enzymes superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPX1), and transcriptional regulators proliferator-activated receptor gamma coactivator 1-α (PGC-1α) and forkhead box protein O1 (FOXO1), which play important roles in oxidative stress response and are known to be O-GlcNAc-modified. 25453190 3 12 dep enzymes 514:520 arg1 CAT 563:565 CAT 563:565 CAT 563:565 The study focused on antioxidant enzymes superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPX1), and transcriptional regulators proliferator-activated receptor gamma coactivator 1-α (PGC-1α) and forkhead box protein O1 (FOXO1), which play important roles in oxidative stress response and are known to be O-GlcNAc-modified. 25453190 3 12 dep enzymes 514:520 arg1 O1 725:726 forkhead box protein O1 704:726 forkhead box protein O1 (FOXO1) 704:734 The study focused on antioxidant enzymes superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPX1), and transcriptional regulators proliferator-activated receptor gamma coactivator 1-α (PGC-1α) and forkhead box protein O1 (FOXO1), which play important roles in oxidative stress response and are known to be O-GlcNAc-modified. 25453190 4 13 theme diethyl 936:942 arg1 maleate 944:950 diethyl maleate 936:950 diethyl maleate 936:950 C2C12 myoblasts were subjected to 24 h incubation with different reagents, including hydrogen peroxide, diethyl maleate, high glucose, and glucosamine, and the inhibitors of O-GlcNAc cycling enzymes. 25453190 2 14 with crosstalk 435:443 arg1 system 473:478 endogenous antioxidant system 450:478 endogenous antioxidant system 450:478 Here we investigated protein O-GlcNAcylation in skeletal muscle cells exposed to oxidative stress and the crosstalk with endogenous antioxidant system. 25453190 1 15 link O-linked 219:226 arg1 O-GlcNAc 251:258 O-GlcNAc 251:258 O-GlcNAc 251:258 A growing body of evidence demonstrates the involvement of protein modification with O-linked β-N-acetylglucosamine (O-GlcNAc) in the stress response and its beneficial effects on cell survival. 25453190 1 15 link O-linked 219:226 arg1 β-N-acetylglucosamine 228:248 O-linked β-N-acetylglucosamine 219:248 O-linked β-N-acetylglucosamine (O-GlcNAc) 219:259 A growing body of evidence demonstrates the involvement of protein modification with O-linked β-N-acetylglucosamine (O-GlcNAc) in the stress response and its beneficial effects on cell survival. 25453190 7 16 theme O-GlcNAc 1426:1433 arg1 role 1418:1421 a role 1416:1421 a role of O-GlcNAc in the stress response 1416:1456 Our findings suggest a role of O-GlcNAc in the stress response and indicate an inhibitory mechanism controlling O-GlcNAc levels in the muscle cells. 25453190 4 17 theme high 953:956 arg1 glucose 958:964 high glucose 953:964 high glucose 953:964 C2C12 myoblasts were subjected to 24 h incubation with different reagents, including hydrogen peroxide, diethyl maleate, high glucose, and glucosamine, and the inhibitors of O-GlcNAc cycling enzymes. 25453190 6 18 theme O-GlcNAc 1255:1262 arg1 enzymes 1264:1270 O-GlcNAc enzymes 1255:1270 O-GlcNAc enzymes 1255:1270 Significant changes at the mRNA level were observed with concomitant upregulation of the genes for O-GlcNAc enzymes and stress-related proteins with oxidizing agents and downregulation of these genes with agents promoting O-GlcNAcylation. 25453190 3 19 theme antioxidant 502:512 arg1 enzymes 514:520 antioxidant enzymes 502:520 antioxidant enzymes superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPX1) 502:603 The study focused on antioxidant enzymes superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPX1), and transcriptional regulators proliferator-activated receptor gamma coactivator 1-α (PGC-1α) and forkhead box protein O1 (FOXO1), which play important roles in oxidative stress response and are known to be O-GlcNAc-modified. 25453190 3 19 theme antioxidant 502:512 arg1 coactivator 675:685 proliferator-activated receptor gamma coactivator 1-α (PGC-1α) 637:698 proliferator-activated receptor gamma coactivator 1-α (PGC-1α) 637:698 The study focused on antioxidant enzymes superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPX1), and transcriptional regulators proliferator-activated receptor gamma coactivator 1-α (PGC-1α) and forkhead box protein O1 (FOXO1), which play important roles in oxidative stress response and are known to be O-GlcNAc-modified. 25453190 3 19 theme antioxidant 502:512 arg1 peroxidase 585:594 glutathione peroxidase 1 573:596 glutathione peroxidase 1 (GPX1) 573:603 The study focused on antioxidant enzymes superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPX1), and transcriptional regulators proliferator-activated receptor gamma coactivator 1-α (PGC-1α) and forkhead box protein O1 (FOXO1), which play important roles in oxidative stress response and are known to be O-GlcNAc-modified. 25453190 3 19 theme antioxidant 502:512 arg1 dismutase 533:541 superoxide dismutase 2 522:543 superoxide dismutase 2 (SOD2) 522:550 The study focused on antioxidant enzymes superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPX1), and transcriptional regulators proliferator-activated receptor gamma coactivator 1-α (PGC-1α) and forkhead box protein O1 (FOXO1), which play important roles in oxidative stress response and are known to be O-GlcNAc-modified. 25453190 3 19 theme antioxidant 502:512 arg1 catalase 553:560 catalase 553:560 catalase (CAT) 553:566 The study focused on antioxidant enzymes superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPX1), and transcriptional regulators proliferator-activated receptor gamma coactivator 1-α (PGC-1α) and forkhead box protein O1 (FOXO1), which play important roles in oxidative stress response and are known to be O-GlcNAc-modified. 25453190 3 19 theme antioxidant 502:512 arg1 O1 725:726 forkhead box protein O1 704:726 forkhead box protein O1 (FOXO1) 704:734 The study focused on antioxidant enzymes superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPX1), and transcriptional regulators proliferator-activated receptor gamma coactivator 1-α (PGC-1α) and forkhead box protein O1 (FOXO1), which play important roles in oxidative stress response and are known to be O-GlcNAc-modified. 25453190 2 20 theme oxidative 410:418 arg1 stress 420:425 oxidative stress 410:425 oxidative stress 410:425 Here we investigated protein O-GlcNAcylation in skeletal muscle cells exposed to oxidative stress and the crosstalk with endogenous antioxidant system. 25453190 6 21 theme genes 1245:1249 arg1 upregulation 1225:1236 concomitant upregulation 1213:1236 concomitant upregulation of the genes for O-GlcNAc enzymes and stress-related proteins with oxidizing agents 1213:1320 Significant changes at the mRNA level were observed with concomitant upregulation of the genes for O-GlcNAc enzymes and stress-related proteins with oxidizing agents and downregulation of these genes with agents promoting O-GlcNAcylation. 25453190 6 21 theme genes 1245:1249 arg1 downregulation 1326:1339 downregulation 1326:1339 downregulation of these genes with agents promoting O-GlcNAcylation 1326:1392 Significant changes at the mRNA level were observed with concomitant upregulation of the genes for O-GlcNAc enzymes and stress-related proteins with oxidizing agents and downregulation of these genes with agents promoting O-GlcNAcylation. 25453190 0 22 theme antioxidant 113:123 arg1 defense 125:131 endogenous antioxidant defense 102:131 endogenous antioxidant defense 102:131 O-GlcNAc protein modification in C2C12 myoblasts exposed to oxidative stress indicates parallels with endogenous antioxidant defense. 25453190 4 23 theme O-GlcNAc 1006:1013 arg1 enzymes 1023:1029 O-GlcNAc cycling enzymes 1006:1029 O-GlcNAc cycling enzymes 1006:1029 C2C12 myoblasts were subjected to 24 h incubation with different reagents, including hydrogen peroxide, diethyl maleate, high glucose, and glucosamine, and the inhibitors of O-GlcNAc cycling enzymes. 25453190 4 24 with inhibitors 992:1001 arg1 reagents 897:904 different reagents 887:904 different reagents 887:904 C2C12 myoblasts were subjected to 24 h incubation with different reagents, including hydrogen peroxide, diethyl maleate, high glucose, and glucosamine, and the inhibitors of O-GlcNAc cycling enzymes. 25453190 4 24 with inhibitors 992:1001 arg1 peroxide 926:933 hydrogen peroxide 917:933 hydrogen peroxide 917:933 C2C12 myoblasts were subjected to 24 h incubation with different reagents, including hydrogen peroxide, diethyl maleate, high glucose, and glucosamine, and the inhibitors of O-GlcNAc cycling enzymes. 25453190 4 24 with inhibitors 992:1001 arg1 maleate 944:950 diethyl maleate 936:950 diethyl maleate 936:950 C2C12 myoblasts were subjected to 24 h incubation with different reagents, including hydrogen peroxide, diethyl maleate, high glucose, and glucosamine, and the inhibitors of O-GlcNAc cycling enzymes. 25453190 4 24 with inhibitors 992:1001 arg1 glucose 958:964 high glucose 953:964 high glucose 953:964 C2C12 myoblasts were subjected to 24 h incubation with different reagents, including hydrogen peroxide, diethyl maleate, high glucose, and glucosamine, and the inhibitors of O-GlcNAc cycling enzymes. 25453190 4 24 with inhibitors 992:1001 arg1 glucosamine 971:981 glucosamine 971:981 glucosamine 971:981 C2C12 myoblasts were subjected to 24 h incubation with different reagents, including hydrogen peroxide, diethyl maleate, high glucose, and glucosamine, and the inhibitors of O-GlcNAc cycling enzymes. 25453190 7 25 theme stress 1442:1447 arg1 response 1449:1456 the stress response 1438:1456 the stress response 1438:1456 Our findings suggest a role of O-GlcNAc in the stress response and indicate an inhibitory mechanism controlling O-GlcNAc levels in the muscle cells. 25453190 7 26 theme O-GlcNAc 1507:1514 arg1 levels 1516:1521 O-GlcNAc levels 1507:1521 O-GlcNAc levels 1507:1521 Our findings suggest a role of O-GlcNAc in the stress response and indicate an inhibitory mechanism controlling O-GlcNAc levels in the muscle cells. 25453190 0 27 theme protein 9:15 arg1 modification 17:28 O-GlcNAc protein modification 0:28 O-GlcNAc protein modification in C2C12 myoblasts exposed to oxidative stress 0:75 O-GlcNAc protein modification in C2C12 myoblasts exposed to oxidative stress indicates parallels with endogenous antioxidant defense. 25453190 6 28 theme Significant 1156:1166 arg1 changes 1168:1174 Significant changes 1156:1174 Significant changes at the mRNA level 1156:1192 Significant changes at the mRNA level were observed with concomitant upregulation of the genes for O-GlcNAc enzymes and stress-related proteins with oxidizing agents and downregulation of these genes with agents promoting O-GlcNAcylation. 25453190 8 29 theme homeostatic 1578:1588 arg1 regulation 1590:1599 an important homeostatic regulation 1565:1599 an important homeostatic regulation of the cellular defense system 1565:1630 This could represent an important homeostatic regulation of the cellular defense system. 25453190 3 30 theme glutathione 573:583 arg1 GPX1 599:602 GPX1 599:602 GPX1 599:602 The study focused on antioxidant enzymes superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPX1), and transcriptional regulators proliferator-activated receptor gamma coactivator 1-α (PGC-1α) and forkhead box protein O1 (FOXO1), which play important roles in oxidative stress response and are known to be O-GlcNAc-modified. 25453190 3 30 theme glutathione 573:583 arg1 enzymes 514:520 antioxidant enzymes 502:520 antioxidant enzymes superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPX1) 502:603 The study focused on antioxidant enzymes superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPX1), and transcriptional regulators proliferator-activated receptor gamma coactivator 1-α (PGC-1α) and forkhead box protein O1 (FOXO1), which play important roles in oxidative stress response and are known to be O-GlcNAc-modified. 25453190 3 30 theme glutathione 573:583 arg1 peroxidase 585:594 glutathione peroxidase 1 573:596 glutathione peroxidase 1 (GPX1) 573:603 The study focused on antioxidant enzymes superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPX1), and transcriptional regulators proliferator-activated receptor gamma coactivator 1-α (PGC-1α) and forkhead box protein O1 (FOXO1), which play important roles in oxidative stress response and are known to be O-GlcNAc-modified. 25453190 6 31 with genes 1350:1354 arg1 agents 1361:1366 agents 1361:1366 agents promoting O-GlcNAcylation 1361:1392 Significant changes at the mRNA level were observed with concomitant upregulation of the genes for O-GlcNAc enzymes and stress-related proteins with oxidizing agents and downregulation of these genes with agents promoting O-GlcNAcylation. 25453190 1 32 theme protein 193:199 arg1 modification 201:212 protein modification 193:212 protein modification with O-linked β-N-acetylglucosamine (O-GlcNAc) 193:259 A growing body of evidence demonstrates the involvement of protein modification with O-linked β-N-acetylglucosamine (O-GlcNAc) in the stress response and its beneficial effects on cell survival. 25453190 0 33 theme O-GlcNAc 0:7 arg1 modification 17:28 O-GlcNAc protein modification 0:28 O-GlcNAc protein modification in C2C12 myoblasts exposed to oxidative stress 0:75 O-GlcNAc protein modification in C2C12 myoblasts exposed to oxidative stress indicates parallels with endogenous antioxidant defense. 25453190 1 34 theme beneficial 292:301 arg1 effects 303:309 its beneficial effects 288:309 its beneficial effects on cell survival 288:326 A growing body of evidence demonstrates the involvement of protein modification with O-linked β-N-acetylglucosamine (O-GlcNAc) in the stress response and its beneficial effects on cell survival. 25453190 1 35 from effects 303:309 arg1 survival 319:326 cell survival 314:326 cell survival 314:326 A growing body of evidence demonstrates the involvement of protein modification with O-linked β-N-acetylglucosamine (O-GlcNAc) in the stress response and its beneficial effects on cell survival. 25453190 7 36 from role 1418:1421 arg1 response 1449:1456 the stress response 1438:1456 the stress response 1438:1456 Our findings suggest a role of O-GlcNAc in the stress response and indicate an inhibitory mechanism controlling O-GlcNAc levels in the muscle cells. 25453190 1 37 theme modification 201:212 arg1 involvement 178:188 the involvement 174:188 the involvement of protein modification with O-linked β-N-acetylglucosamine (O-GlcNAc) in the stress response and its beneficial effects on cell survival 174:326 A growing body of evidence demonstrates the involvement of protein modification with O-linked β-N-acetylglucosamine (O-GlcNAc) in the stress response and its beneficial effects on cell survival. 25453190 4 38 theme enzymes 1023:1029 arg1 inhibitors 992:1001 the inhibitors 988:1001 the inhibitors of O-GlcNAc cycling enzymes 988:1029 C2C12 myoblasts were subjected to 24 h incubation with different reagents, including hydrogen peroxide, diethyl maleate, high glucose, and glucosamine, and the inhibitors of O-GlcNAc cycling enzymes. 25453190 4 38 theme enzymes 1023:1029 arg1 incubation 871:880 24 h incubation 866:880 24 h incubation with different reagents, including hydrogen peroxide, diethyl maleate, high glucose, and glucosamine, 866:982 C2C12 myoblasts were subjected to 24 h incubation with different reagents, including hydrogen peroxide, diethyl maleate, high glucose, and glucosamine, and the inhibitors of O-GlcNAc cycling enzymes. 25453190 3 39 theme important 748:756 arg1 roles 758:762 important roles 748:762 important roles 748:762 The study focused on antioxidant enzymes superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPX1), and transcriptional regulators proliferator-activated receptor gamma coactivator 1-α (PGC-1α) and forkhead box protein O1 (FOXO1), which play important roles in oxidative stress response and are known to be O-GlcNAc-modified. 25453190 4 40 theme hydrogen 917:924 arg1 peroxide 926:933 hydrogen peroxide 917:933 hydrogen peroxide 917:933 C2C12 myoblasts were subjected to 24 h incubation with different reagents, including hydrogen peroxide, diethyl maleate, high glucose, and glucosamine, and the inhibitors of O-GlcNAc cycling enzymes. 25453190 6 41 theme concomitant 1213:1223 arg1 upregulation 1225:1236 concomitant upregulation 1213:1236 concomitant upregulation of the genes for O-GlcNAc enzymes and stress-related proteins with oxidizing agents 1213:1320 Significant changes at the mRNA level were observed with concomitant upregulation of the genes for O-GlcNAc enzymes and stress-related proteins with oxidizing agents and downregulation of these genes with agents promoting O-GlcNAcylation. 25453190 2 42 theme endogenous 450:459 arg1 system 473:478 endogenous antioxidant system 450:478 endogenous antioxidant system 450:478 Here we investigated protein O-GlcNAcylation in skeletal muscle cells exposed to oxidative stress and the crosstalk with endogenous antioxidant system. 25453190 2 43 theme antioxidant 461:471 arg1 system 473:478 endogenous antioxidant system 450:478 endogenous antioxidant system 450:478 Here we investigated protein O-GlcNAcylation in skeletal muscle cells exposed to oxidative stress and the crosstalk with endogenous antioxidant system. 25453190 5 44 theme other 1121:1125 arg1 treatments 1127:1136 other treatments 1121:1136 other treatments 1121:1136 Surprisingly, O-GlcNAc levels were significantly increased only with glucosamine, whilst other treatments showed no effect. 25453190 6 45 theme genes 1350:1354 arg1 upregulation 1225:1236 concomitant upregulation 1213:1236 concomitant upregulation of the genes for O-GlcNAc enzymes and stress-related proteins with oxidizing agents 1213:1320 Significant changes at the mRNA level were observed with concomitant upregulation of the genes for O-GlcNAc enzymes and stress-related proteins with oxidizing agents and downregulation of these genes with agents promoting O-GlcNAcylation. 25453190 6 45 theme genes 1350:1354 arg1 downregulation 1326:1339 downregulation 1326:1339 downregulation of these genes with agents promoting O-GlcNAcylation 1326:1392 Significant changes at the mRNA level were observed with concomitant upregulation of the genes for O-GlcNAc enzymes and stress-related proteins with oxidizing agents and downregulation of these genes with agents promoting O-GlcNAcylation. 25453190 3 46 theme gamma 669:673 arg1 enzymes 514:520 antioxidant enzymes 502:520 antioxidant enzymes superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPX1) 502:603 The study focused on antioxidant enzymes superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPX1), and transcriptional regulators proliferator-activated receptor gamma coactivator 1-α (PGC-1α) and forkhead box protein O1 (FOXO1), which play important roles in oxidative stress response and are known to be O-GlcNAc-modified. 25453190 3 46 theme gamma 669:673 arg1 coactivator 675:685 proliferator-activated receptor gamma coactivator 1-α (PGC-1α) 637:698 proliferator-activated receptor gamma coactivator 1-α (PGC-1α) 637:698 The study focused on antioxidant enzymes superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPX1), and transcriptional regulators proliferator-activated receptor gamma coactivator 1-α (PGC-1α) and forkhead box protein O1 (FOXO1), which play important roles in oxidative stress response and are known to be O-GlcNAc-modified. 25453190 1 47 theme O-linked 219:226 arg1 O-GlcNAc 251:258 O-GlcNAc 251:258 O-GlcNAc 251:258 A growing body of evidence demonstrates the involvement of protein modification with O-linked β-N-acetylglucosamine (O-GlcNAc) in the stress response and its beneficial effects on cell survival. 25453190 1 47 theme O-linked 219:226 arg1 β-N-acetylglucosamine 228:248 O-linked β-N-acetylglucosamine 219:248 O-linked β-N-acetylglucosamine (O-GlcNAc) 219:259 A growing body of evidence demonstrates the involvement of protein modification with O-linked β-N-acetylglucosamine (O-GlcNAc) in the stress response and its beneficial effects on cell survival. 25453190 1 48 theme cell 314:317 arg1 survival 319:326 cell survival 314:326 cell survival 314:326 A growing body of evidence demonstrates the involvement of protein modification with O-linked β-N-acetylglucosamine (O-GlcNAc) in the stress response and its beneficial effects on cell survival. 25453190 0 49 theme C2C12 33:37 arg1 myoblasts 39:47 C2C12 myoblasts 33:47 C2C12 myoblasts exposed to oxidative stress 33:75 O-GlcNAc protein modification in C2C12 myoblasts exposed to oxidative stress indicates parallels with endogenous antioxidant defense. 25453190 3 50 theme oxidative 767:775 arg1 response 784:791 oxidative stress response 767:791 oxidative stress response 767:791 The study focused on antioxidant enzymes superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPX1), and transcriptional regulators proliferator-activated receptor gamma coactivator 1-α (PGC-1α) and forkhead box protein O1 (FOXO1), which play important roles in oxidative stress response and are known to be O-GlcNAc-modified. 25453190 1 51 from response 275:282 arg1 survival 319:326 cell survival 314:326 cell survival 314:326 A growing body of evidence demonstrates the involvement of protein modification with O-linked β-N-acetylglucosamine (O-GlcNAc) in the stress response and its beneficial effects on cell survival. 25453190 3 52 theme proliferator-activated 637:658 arg1 enzymes 514:520 antioxidant enzymes 502:520 antioxidant enzymes superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPX1) 502:603 The study focused on antioxidant enzymes superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPX1), and transcriptional regulators proliferator-activated receptor gamma coactivator 1-α (PGC-1α) and forkhead box protein O1 (FOXO1), which play important roles in oxidative stress response and are known to be O-GlcNAc-modified. 25453190 3 52 theme proliferator-activated 637:658 arg1 coactivator 675:685 proliferator-activated receptor gamma coactivator 1-α (PGC-1α) 637:698 proliferator-activated receptor gamma coactivator 1-α (PGC-1α) 637:698 The study focused on antioxidant enzymes superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPX1), and transcriptional regulators proliferator-activated receptor gamma coactivator 1-α (PGC-1α) and forkhead box protein O1 (FOXO1), which play important roles in oxidative stress response and are known to be O-GlcNAc-modified. 25453190 3 53 theme stress 777:782 arg1 response 784:791 oxidative stress response 767:791 oxidative stress response 767:791 The study focused on antioxidant enzymes superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPX1), and transcriptional regulators proliferator-activated receptor gamma coactivator 1-α (PGC-1α) and forkhead box protein O1 (FOXO1), which play important roles in oxidative stress response and are known to be O-GlcNAc-modified. 25453190 4 54 theme different 887:895 arg1 reagents 897:904 different reagents 887:904 different reagents 887:904 C2C12 myoblasts were subjected to 24 h incubation with different reagents, including hydrogen peroxide, diethyl maleate, high glucose, and glucosamine, and the inhibitors of O-GlcNAc cycling enzymes. 25453190 4 54 theme different 887:895 arg1 peroxide 926:933 hydrogen peroxide 917:933 hydrogen peroxide 917:933 C2C12 myoblasts were subjected to 24 h incubation with different reagents, including hydrogen peroxide, diethyl maleate, high glucose, and glucosamine, and the inhibitors of O-GlcNAc cycling enzymes. 25453190 4 54 theme different 887:895 arg1 maleate 944:950 diethyl maleate 936:950 diethyl maleate 936:950 C2C12 myoblasts were subjected to 24 h incubation with different reagents, including hydrogen peroxide, diethyl maleate, high glucose, and glucosamine, and the inhibitors of O-GlcNAc cycling enzymes. 25453190 4 54 theme different 887:895 arg1 glucose 958:964 high glucose 953:964 high glucose 953:964 C2C12 myoblasts were subjected to 24 h incubation with different reagents, including hydrogen peroxide, diethyl maleate, high glucose, and glucosamine, and the inhibitors of O-GlcNAc cycling enzymes. 25453190 4 54 theme different 887:895 arg1 glucosamine 971:981 glucosamine 971:981 glucosamine 971:981 C2C12 myoblasts were subjected to 24 h incubation with different reagents, including hydrogen peroxide, diethyl maleate, high glucose, and glucosamine, and the inhibitors of O-GlcNAc cycling enzymes. 25453190 3 55 theme receptor 660:667 arg1 enzymes 514:520 antioxidant enzymes 502:520 antioxidant enzymes superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPX1) 502:603 The study focused on antioxidant enzymes superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPX1), and transcriptional regulators proliferator-activated receptor gamma coactivator 1-α (PGC-1α) and forkhead box protein O1 (FOXO1), which play important roles in oxidative stress response and are known to be O-GlcNAc-modified. 25453190 3 55 theme receptor 660:667 arg1 coactivator 675:685 proliferator-activated receptor gamma coactivator 1-α (PGC-1α) 637:698 proliferator-activated receptor gamma coactivator 1-α (PGC-1α) 637:698 The study focused on antioxidant enzymes superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPX1), and transcriptional regulators proliferator-activated receptor gamma coactivator 1-α (PGC-1α) and forkhead box protein O1 (FOXO1), which play important roles in oxidative stress response and are known to be O-GlcNAc-modified. 25453190 3 56 theme forkhead 704:711 arg1 enzymes 514:520 antioxidant enzymes 502:520 antioxidant enzymes superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPX1) 502:603 The study focused on antioxidant enzymes superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPX1), and transcriptional regulators proliferator-activated receptor gamma coactivator 1-α (PGC-1α) and forkhead box protein O1 (FOXO1), which play important roles in oxidative stress response and are known to be O-GlcNAc-modified. 25453190 3 56 theme forkhead 704:711 arg1 FOXO1 729:733 FOXO1 729:733 FOXO1 729:733 The study focused on antioxidant enzymes superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPX1), and transcriptional regulators proliferator-activated receptor gamma coactivator 1-α (PGC-1α) and forkhead box protein O1 (FOXO1), which play important roles in oxidative stress response and are known to be O-GlcNAc-modified. 25453190 3 56 theme forkhead 704:711 arg1 O1 725:726 forkhead box protein O1 704:726 forkhead box protein O1 (FOXO1) 704:734 The study focused on antioxidant enzymes superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPX1), and transcriptional regulators proliferator-activated receptor gamma coactivator 1-α (PGC-1α) and forkhead box protein O1 (FOXO1), which play important roles in oxidative stress response and are known to be O-GlcNAc-modified. 25453190 8 57 theme system 1625:1630 arg1 regulation 1590:1599 an important homeostatic regulation 1565:1599 an important homeostatic regulation of the cellular defense system 1565:1630 This could represent an important homeostatic regulation of the cellular defense system. 25453190 1 58 with modification 201:212 arg1 O-GlcNAc 251:258 O-GlcNAc 251:258 O-GlcNAc 251:258 A growing body of evidence demonstrates the involvement of protein modification with O-linked β-N-acetylglucosamine (O-GlcNAc) in the stress response and its beneficial effects on cell survival. 25453190 1 58 with modification 201:212 arg1 β-N-acetylglucosamine 228:248 O-linked β-N-acetylglucosamine 219:248 O-linked β-N-acetylglucosamine (O-GlcNAc) 219:259 A growing body of evidence demonstrates the involvement of protein modification with O-linked β-N-acetylglucosamine (O-GlcNAc) in the stress response and its beneficial effects on cell survival. 25453190 4 59 theme C2C12 832:836 arg1 myoblasts 838:846 C2C12 myoblasts 832:846 C2C12 myoblasts 832:846 C2C12 myoblasts were subjected to 24 h incubation with different reagents, including hydrogen peroxide, diethyl maleate, high glucose, and glucosamine, and the inhibitors of O-GlcNAc cycling enzymes. 25453190 6 60 theme stress-related 1276:1289 arg1 proteins 1291:1298 stress-related proteins 1276:1298 stress-related proteins 1276:1298 Significant changes at the mRNA level were observed with concomitant upregulation of the genes for O-GlcNAc enzymes and stress-related proteins with oxidizing agents and downregulation of these genes with agents promoting O-GlcNAcylation. 25453190 4 61 with incubation 871:880 arg1 reagents 897:904 different reagents 887:904 different reagents 887:904 C2C12 myoblasts were subjected to 24 h incubation with different reagents, including hydrogen peroxide, diethyl maleate, high glucose, and glucosamine, and the inhibitors of O-GlcNAc cycling enzymes. 25453190 4 61 with incubation 871:880 arg1 peroxide 926:933 hydrogen peroxide 917:933 hydrogen peroxide 917:933 C2C12 myoblasts were subjected to 24 h incubation with different reagents, including hydrogen peroxide, diethyl maleate, high glucose, and glucosamine, and the inhibitors of O-GlcNAc cycling enzymes. 25453190 4 61 with incubation 871:880 arg1 maleate 944:950 diethyl maleate 936:950 diethyl maleate 936:950 C2C12 myoblasts were subjected to 24 h incubation with different reagents, including hydrogen peroxide, diethyl maleate, high glucose, and glucosamine, and the inhibitors of O-GlcNAc cycling enzymes. 25453190 4 61 with incubation 871:880 arg1 glucose 958:964 high glucose 953:964 high glucose 953:964 C2C12 myoblasts were subjected to 24 h incubation with different reagents, including hydrogen peroxide, diethyl maleate, high glucose, and glucosamine, and the inhibitors of O-GlcNAc cycling enzymes. 25453190 4 61 with incubation 871:880 arg1 glucosamine 971:981 glucosamine 971:981 glucosamine 971:981 C2C12 myoblasts were subjected to 24 h incubation with different reagents, including hydrogen peroxide, diethyl maleate, high glucose, and glucosamine, and the inhibitors of O-GlcNAc cycling enzymes. 25453190 8 62 theme defense 1617:1623 arg1 system 1625:1630 the cellular defense system 1604:1630 the cellular defense system 1604:1630 This could represent an important homeostatic regulation of the cellular defense system. 25453190 3 63 theme transcriptional 610:624 arg1 regulators 626:635 transcriptional regulators 610:635 transcriptional regulators 610:635 The study focused on antioxidant enzymes superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPX1), and transcriptional regulators proliferator-activated receptor gamma coactivator 1-α (PGC-1α) and forkhead box protein O1 (FOXO1), which play important roles in oxidative stress response and are known to be O-GlcNAc-modified. 25453190 1 64 theme growing 136:142 arg1 body 144:147 A growing body 134:147 A growing body of evidence 134:159 A growing body of evidence demonstrates the involvement of protein modification with O-linked β-N-acetylglucosamine (O-GlcNAc) in the stress response and its beneficial effects on cell survival. 25453190 6 65 theme oxidizing 1305:1313 arg1 agents 1315:1320 oxidizing agents 1305:1320 oxidizing agents 1305:1320 Significant changes at the mRNA level were observed with concomitant upregulation of the genes for O-GlcNAc enzymes and stress-related proteins with oxidizing agents and downregulation of these genes with agents promoting O-GlcNAcylation. 25453190 6 66 theme mRNA 1183:1186 arg1 level 1188:1192 the mRNA level 1179:1192 the mRNA level 1179:1192 Significant changes at the mRNA level were observed with concomitant upregulation of the genes for O-GlcNAc enzymes and stress-related proteins with oxidizing agents and downregulation of these genes with agents promoting O-GlcNAcylation. 25453190 3 67 theme superoxide 522:531 arg1 dismutase 533:541 superoxide dismutase 2 522:543 superoxide dismutase 2 (SOD2) 522:550 The study focused on antioxidant enzymes superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPX1), and transcriptional regulators proliferator-activated receptor gamma coactivator 1-α (PGC-1α) and forkhead box protein O1 (FOXO1), which play important roles in oxidative stress response and are known to be O-GlcNAc-modified. 25453190 3 67 theme superoxide 522:531 arg1 SOD2 546:549 SOD2 546:549 SOD2 546:549 The study focused on antioxidant enzymes superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPX1), and transcriptional regulators proliferator-activated receptor gamma coactivator 1-α (PGC-1α) and forkhead box protein O1 (FOXO1), which play important roles in oxidative stress response and are known to be O-GlcNAc-modified. 25453190 3 67 theme superoxide 522:531 arg1 enzymes 514:520 antioxidant enzymes 502:520 antioxidant enzymes superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPX1) 502:603 The study focused on antioxidant enzymes superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPX1), and transcriptional regulators proliferator-activated receptor gamma coactivator 1-α (PGC-1α) and forkhead box protein O1 (FOXO1), which play important roles in oxidative stress response and are known to be O-GlcNAc-modified. 25453190 4 68 theme h 869:869 arg1 incubation 871:880 24 h incubation 866:880 24 h incubation with different reagents, including hydrogen peroxide, diethyl maleate, high glucose, and glucosamine, 866:982 C2C12 myoblasts were subjected to 24 h incubation with different reagents, including hydrogen peroxide, diethyl maleate, high glucose, and glucosamine, and the inhibitors of O-GlcNAc cycling enzymes. 25453190 2 69 theme protein 350:356 arg1 O-GlcNAcylation 358:372 protein O-GlcNAcylation 350:372 protein O-GlcNAcylation 350:372 Here we investigated protein O-GlcNAcylation in skeletal muscle cells exposed to oxidative stress and the crosstalk with endogenous antioxidant system. 25453190 7 70 theme inhibitory 1474:1483 arg1 mechanism 1485:1493 an inhibitory mechanism 1471:1493 an inhibitory mechanism controlling O-GlcNAc levels in the muscle cells 1471:1541 Our findings suggest a role of O-GlcNAc in the stress response and indicate an inhibitory mechanism controlling O-GlcNAc levels in the muscle cells. 25453190 5 71 theme O-GlcNAc 1046:1053 arg1 levels 1055:1060 O-GlcNAc levels 1046:1060 O-GlcNAc levels 1046:1060 Surprisingly, O-GlcNAc levels were significantly increased only with glucosamine, whilst other treatments showed no effect. 25453190 8 72 theme important 1568:1576 arg1 regulation 1590:1599 an important homeostatic regulation 1565:1599 an important homeostatic regulation of the cellular defense system 1565:1630 This could represent an important homeostatic regulation of the cellular defense system. 25453190 6 73 with proteins 1291:1298 arg1 agents 1315:1320 oxidizing agents 1305:1320 oxidizing agents 1305:1320 Significant changes at the mRNA level were observed with concomitant upregulation of the genes for O-GlcNAc enzymes and stress-related proteins with oxidizing agents and downregulation of these genes with agents promoting O-GlcNAcylation. 25453190 8 74 theme cellular 1608:1615 arg1 system 1625:1630 the cellular defense system 1604:1630 the cellular defense system 1604:1630 This could represent an important homeostatic regulation of the cellular defense system. 25453190 0 75 theme oxidative 60:68 arg1 stress 70:75 oxidative stress 60:75 oxidative stress 60:75 O-GlcNAc protein modification in C2C12 myoblasts exposed to oxidative stress indicates parallels with endogenous antioxidant defense. 25453190 3 76 theme box 713:715 arg1 enzymes 514:520 antioxidant enzymes 502:520 antioxidant enzymes superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPX1) 502:603 The study focused on antioxidant enzymes superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPX1), and transcriptional regulators proliferator-activated receptor gamma coactivator 1-α (PGC-1α) and forkhead box protein O1 (FOXO1), which play important roles in oxidative stress response and are known to be O-GlcNAc-modified. 25453190 3 76 theme box 713:715 arg1 FOXO1 729:733 FOXO1 729:733 FOXO1 729:733 The study focused on antioxidant enzymes superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPX1), and transcriptional regulators proliferator-activated receptor gamma coactivator 1-α (PGC-1α) and forkhead box protein O1 (FOXO1), which play important roles in oxidative stress response and are known to be O-GlcNAc-modified. 25453190 3 76 theme box 713:715 arg1 O1 725:726 forkhead box protein O1 704:726 forkhead box protein O1 (FOXO1) 704:734 The study focused on antioxidant enzymes superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPX1), and transcriptional regulators proliferator-activated receptor gamma coactivator 1-α (PGC-1α) and forkhead box protein O1 (FOXO1), which play important roles in oxidative stress response and are known to be O-GlcNAc-modified. 25453190 4 77 theme cycling 1015:1021 arg1 enzymes 1023:1029 O-GlcNAc cycling enzymes 1006:1029 O-GlcNAc cycling enzymes 1006:1029 C2C12 myoblasts were subjected to 24 h incubation with different reagents, including hydrogen peroxide, diethyl maleate, high glucose, and glucosamine, and the inhibitors of O-GlcNAc cycling enzymes. 25453190 1 78 from involvement 178:188 arg1 response 275:282 the stress response 264:282 the stress response 264:282 A growing body of evidence demonstrates the involvement of protein modification with O-linked β-N-acetylglucosamine (O-GlcNAc) in the stress response and its beneficial effects on cell survival. 25453190 1 78 from involvement 178:188 arg1 effects 303:309 its beneficial effects 288:309 its beneficial effects on cell survival 288:326 A growing body of evidence demonstrates the involvement of protein modification with O-linked β-N-acetylglucosamine (O-GlcNAc) in the stress response and its beneficial effects on cell survival. 25453190 1 78 from involvement 178:188 arg1 survival 319:326 cell survival 314:326 cell survival 314:326 A growing body of evidence demonstrates the involvement of protein modification with O-linked β-N-acetylglucosamine (O-GlcNAc) in the stress response and its beneficial effects on cell survival. 25453190 1 79 theme evidence 152:159 arg1 body 144:147 A growing body 134:147 A growing body of evidence 134:159 A growing body of evidence demonstrates the involvement of protein modification with O-linked β-N-acetylglucosamine (O-GlcNAc) in the stress response and its beneficial effects on cell survival. 25453190 7 80 theme muscle 1530:1535 arg1 cells 1537:1541 the muscle cells 1526:1541 the muscle cells 1526:1541 Our findings suggest a role of O-GlcNAc in the stress response and indicate an inhibitory mechanism controlling O-GlcNAc levels in the muscle cells. 25419848 5 0 theme O-GlcNAcylated 820:833 arg1 levels 843:848 O-GlcNAcylated SNAP-29 levels 820:848 O-GlcNAcylated SNAP-29 levels 820:848 O-GlcNAcylated SNAP-29 levels are reduced during starvation in mammalian cells and in C. elegans. 25419848 6 1 theme nutrient 990:997 arg1 status 999:1004 nutrient status 990:1004 nutrient status 990:1004 Our study reveals a mechanism by which O-GlcNAc-modification integrates nutrient status with autophagosome maturation. 25419848 5 2 theme SNAP-29 835:841 arg1 levels 843:848 O-GlcNAcylated SNAP-29 levels 820:848 O-GlcNAcylated SNAP-29 levels 820:848 O-GlcNAcylated SNAP-29 levels are reduced during starvation in mammalian cells and in C. elegans. 25419848 2 3 from autophagy 343:351 arg1 manner 377:382 a nutrient-dependent manner 356:382 a nutrient-dependent manner 356:382 Here, we report that O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) mediates O-GlcNAcylation of the SNARE protein SNAP-29 and regulates autophagy in a nutrient-dependent manner. 25419848 3 4 theme mammalian 388:396 arg1 cells 398:402 mammalian cells 388:402 mammalian cells 388:402 In mammalian cells, OGT knockdown, or mutating the O-GlcNAc sites in SNAP-29, promotes the formation of a SNAP-29-containing SNARE complex, increases fusion between autophagosomes and endosomes/lysosomes, and promotes autophagic flux. 25419848 3 5 dep knockdown 409:417 arg1 mutating 423:430 mutating 423:430 mutating the O-GlcNAc sites in SNAP-29 423:460 In mammalian cells, OGT knockdown, or mutating the O-GlcNAc sites in SNAP-29, promotes the formation of a SNAP-29-containing SNARE complex, increases fusion between autophagosomes and endosomes/lysosomes, and promotes autophagic flux. 25419848 2 6 theme protein 313:319 arg1 SNAP-29 321:327 the SNARE protein SNAP-29 303:327 the SNARE protein SNAP-29 303:327 Here, we report that O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) mediates O-GlcNAcylation of the SNARE protein SNAP-29 and regulates autophagy in a nutrient-dependent manner. 25419848 4 7 theme aggregates 808:817 arg1 degradation 785:795 autophagic degradation 774:795 autophagic degradation of protein aggregates 774:817 In Caenorhabditis elegans, depletion of ogt-1 has a similar effect on autophagy; moreover, expression of an O-GlcNAc-defective SNAP-29 mutant facilitates autophagic degradation of protein aggregates. 25419848 2 8 theme SNARE 307:311 arg1 SNAP-29 321:327 the SNARE protein SNAP-29 303:327 the SNARE protein SNAP-29 303:327 Here, we report that O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) mediates O-GlcNAcylation of the SNARE protein SNAP-29 and regulates autophagy in a nutrient-dependent manner. 25419848 4 9 theme Caenorhabditis 623:636 arg1 elegans 638:644 Caenorhabditis elegans 623:644 Caenorhabditis elegans 623:644 In Caenorhabditis elegans, depletion of ogt-1 has a similar effect on autophagy; moreover, expression of an O-GlcNAc-defective SNAP-29 mutant facilitates autophagic degradation of protein aggregates. 25419848 4 10 theme SNAP-29 747:753 arg1 mutant 755:760 an O-GlcNAc-defective SNAP-29 mutant 725:760 an O-GlcNAc-defective SNAP-29 mutant 725:760 In Caenorhabditis elegans, depletion of ogt-1 has a similar effect on autophagy; moreover, expression of an O-GlcNAc-defective SNAP-29 mutant facilitates autophagic degradation of protein aggregates. 25419848 1 11 theme nutrient 92:99 arg1 status 101:106 nutrient status 92:106 nutrient status 92:106 The mechanism by which nutrient status regulates the fusion of autophagosomes with endosomes/lysosomes is poorly understood. 25419848 3 12 theme autophagic 603:612 arg1 flux 614:617 autophagic flux 603:617 autophagic flux 603:617 In mammalian cells, OGT knockdown, or mutating the O-GlcNAc sites in SNAP-29, promotes the formation of a SNAP-29-containing SNARE complex, increases fusion between autophagosomes and endosomes/lysosomes, and promotes autophagic flux. 25419848 1 13 with fusion 122:127 arg1 endosomes/lysosomes 152:170 endosomes/lysosomes 152:170 endosomes/lysosomes 152:170 The mechanism by which nutrient status regulates the fusion of autophagosomes with endosomes/lysosomes is poorly understood. 25419848 4 14 theme mutant 755:760 arg1 expression 711:720 expression 711:720 expression of an O-GlcNAc-defective SNAP-29 mutant 711:760 In Caenorhabditis elegans, depletion of ogt-1 has a similar effect on autophagy; moreover, expression of an O-GlcNAc-defective SNAP-29 mutant facilitates autophagic degradation of protein aggregates. 25419848 4 15 theme autophagic 774:783 arg1 degradation 785:795 autophagic degradation 774:795 autophagic degradation of protein aggregates 774:817 In Caenorhabditis elegans, depletion of ogt-1 has a similar effect on autophagy; moreover, expression of an O-GlcNAc-defective SNAP-29 mutant facilitates autophagic degradation of protein aggregates. 25419848 5 16 theme mammalian 883:891 arg1 cells 893:897 mammalian cells 883:897 mammalian cells 883:897 O-GlcNAcylated SNAP-29 levels are reduced during starvation in mammalian cells and in C. elegans. 25419848 4 17 theme protein 800:806 arg1 aggregates 808:817 protein aggregates 800:817 protein aggregates 800:817 In Caenorhabditis elegans, depletion of ogt-1 has a similar effect on autophagy; moreover, expression of an O-GlcNAc-defective SNAP-29 mutant facilitates autophagic degradation of protein aggregates. 25419848 2 18 link O-linked 215:222 arg1 transferase 257:267 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase 215:267 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) 215:273 Here, we report that O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) mediates O-GlcNAcylation of the SNARE protein SNAP-29 and regulates autophagy in a nutrient-dependent manner. 25419848 2 18 link O-linked 215:222 arg1 OGT 270:272 OGT 270:272 OGT 270:272 Here, we report that O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) mediates O-GlcNAcylation of the SNARE protein SNAP-29 and regulates autophagy in a nutrient-dependent manner. 25419848 3 19 theme OGT 405:407 arg1 knockdown 409:417 OGT knockdown 405:417 OGT knockdown 405:417 In mammalian cells, OGT knockdown, or mutating the O-GlcNAc sites in SNAP-29, promotes the formation of a SNAP-29-containing SNARE complex, increases fusion between autophagosomes and endosomes/lysosomes, and promotes autophagic flux. 25419848 2 20 theme SNAP-29 321:327 arg1 O-GlcNAcylation 284:298 O-GlcNAcylation 284:298 O-GlcNAcylation of the SNARE protein SNAP-29 284:327 Here, we report that O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) mediates O-GlcNAcylation of the SNARE protein SNAP-29 and regulates autophagy in a nutrient-dependent manner. 25419848 1 21 theme autophagosomes 132:145 arg1 fusion 122:127 the fusion 118:127 the fusion of autophagosomes with endosomes/lysosomes 118:170 The mechanism by which nutrient status regulates the fusion of autophagosomes with endosomes/lysosomes is poorly understood. 25419848 5 22 theme C. 906:907 arg1 elegans 909:915 C. elegans 906:915 C. elegans 906:915 O-GlcNAcylated SNAP-29 levels are reduced during starvation in mammalian cells and in C. elegans. 25419848 0 23 theme autophagosome 43:55 arg1 maturation 57:66 autophagosome maturation 43:66 autophagosome maturation 43:66 O-GlcNAc-modification of SNAP-29 regulates autophagosome maturation. 25419848 3 24 theme O-GlcNAc 436:443 arg1 sites 445:449 the O-GlcNAc sites 432:449 the O-GlcNAc sites in SNAP-29 432:460 In mammalian cells, OGT knockdown, or mutating the O-GlcNAc sites in SNAP-29, promotes the formation of a SNAP-29-containing SNARE complex, increases fusion between autophagosomes and endosomes/lysosomes, and promotes autophagic flux. 25419848 4 25 contain has 666:668 arg1 depletion 647:655 depletion 647:655 depletion of ogt-1 647:664 In Caenorhabditis elegans, depletion of ogt-1 has a similar effect on autophagy; moreover, expression of an O-GlcNAc-defective SNAP-29 mutant facilitates autophagic degradation of protein aggregates. 25419848 4 25 contain has 666:668 arg2 effect 680:685 a similar effect 670:685 a similar effect 670:685 In Caenorhabditis elegans, depletion of ogt-1 has a similar effect on autophagy; moreover, expression of an O-GlcNAc-defective SNAP-29 mutant facilitates autophagic degradation of protein aggregates. 25419848 4 26 theme similar 672:678 arg1 effect 680:685 a similar effect 670:685 a similar effect 670:685 In Caenorhabditis elegans, depletion of ogt-1 has a similar effect on autophagy; moreover, expression of an O-GlcNAc-defective SNAP-29 mutant facilitates autophagic degradation of protein aggregates. 25419848 3 27 theme SNARE 510:514 arg1 complex 516:522 a SNAP-29-containing SNARE complex 489:522 a SNAP-29-containing SNARE complex 489:522 In mammalian cells, OGT knockdown, or mutating the O-GlcNAc sites in SNAP-29, promotes the formation of a SNAP-29-containing SNARE complex, increases fusion between autophagosomes and endosomes/lysosomes, and promotes autophagic flux. 25419848 6 28 theme autophagosome 1011:1023 arg1 maturation 1025:1034 autophagosome maturation 1011:1034 autophagosome maturation 1011:1034 Our study reveals a mechanism by which O-GlcNAc-modification integrates nutrient status with autophagosome maturation. 25419848 2 29 theme O-GlcNAc 247:254 arg1 transferase 257:267 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase 215:267 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) 215:273 Here, we report that O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) mediates O-GlcNAcylation of the SNARE protein SNAP-29 and regulates autophagy in a nutrient-dependent manner. 25419848 2 29 theme O-GlcNAc 247:254 arg1 OGT 270:272 OGT 270:272 OGT 270:272 Here, we report that O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) mediates O-GlcNAcylation of the SNARE protein SNAP-29 and regulates autophagy in a nutrient-dependent manner. 25419848 3 30 theme complex 516:522 arg1 formation 476:484 the formation 472:484 the formation of a SNAP-29-containing SNARE complex 472:522 In mammalian cells, OGT knockdown, or mutating the O-GlcNAc sites in SNAP-29, promotes the formation of a SNAP-29-containing SNARE complex, increases fusion between autophagosomes and endosomes/lysosomes, and promotes autophagic flux. 25419848 2 31 theme β-N-acetylglucosamine 224:244 arg1 transferase 257:267 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase 215:267 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) 215:273 Here, we report that O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) mediates O-GlcNAcylation of the SNARE protein SNAP-29 and regulates autophagy in a nutrient-dependent manner. 25419848 2 31 theme β-N-acetylglucosamine 224:244 arg1 OGT 270:272 OGT 270:272 OGT 270:272 Here, we report that O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) mediates O-GlcNAcylation of the SNARE protein SNAP-29 and regulates autophagy in a nutrient-dependent manner. 25419848 2 32 theme O-linked 215:222 arg1 transferase 257:267 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase 215:267 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) 215:273 Here, we report that O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) mediates O-GlcNAcylation of the SNARE protein SNAP-29 and regulates autophagy in a nutrient-dependent manner. 25419848 2 32 theme O-linked 215:222 arg1 OGT 270:272 OGT 270:272 OGT 270:272 Here, we report that O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) mediates O-GlcNAcylation of the SNARE protein SNAP-29 and regulates autophagy in a nutrient-dependent manner. 25419848 3 33 from sites 445:449 arg1 SNAP-29 454:460 SNAP-29 454:460 SNAP-29 454:460 In mammalian cells, OGT knockdown, or mutating the O-GlcNAc sites in SNAP-29, promotes the formation of a SNAP-29-containing SNARE complex, increases fusion between autophagosomes and endosomes/lysosomes, and promotes autophagic flux. 25419848 3 34 theme SNAP-29-containing 491:508 arg1 complex 516:522 a SNAP-29-containing SNARE complex 489:522 a SNAP-29-containing SNARE complex 489:522 In mammalian cells, OGT knockdown, or mutating the O-GlcNAc sites in SNAP-29, promotes the formation of a SNAP-29-containing SNARE complex, increases fusion between autophagosomes and endosomes/lysosomes, and promotes autophagic flux. 25419848 2 35 theme nutrient-dependent 358:375 arg1 manner 377:382 a nutrient-dependent manner 356:382 a nutrient-dependent manner 356:382 Here, we report that O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) mediates O-GlcNAcylation of the SNARE protein SNAP-29 and regulates autophagy in a nutrient-dependent manner. 25419848 4 36 theme ogt-1 660:664 arg1 depletion 647:655 depletion 647:655 depletion of ogt-1 647:664 In Caenorhabditis elegans, depletion of ogt-1 has a similar effect on autophagy; moreover, expression of an O-GlcNAc-defective SNAP-29 mutant facilitates autophagic degradation of protein aggregates. 25419848 0 37 theme SNAP-29 25:31 arg1 O-GlcNAc-modification 0:20 O-GlcNAc-modification 0:20 O-GlcNAc-modification of SNAP-29 0:31 O-GlcNAc-modification of SNAP-29 regulates autophagosome maturation. 25419848 4 38 theme O-GlcNAc-defective 728:745 arg1 mutant 755:760 an O-GlcNAc-defective SNAP-29 mutant 725:760 an O-GlcNAc-defective SNAP-29 mutant 725:760 In Caenorhabditis elegans, depletion of ogt-1 has a similar effect on autophagy; moreover, expression of an O-GlcNAc-defective SNAP-29 mutant facilitates autophagic degradation of protein aggregates. 28271569 4 0 theme FFPE 1026:1029 arg1 sections 1038:1045 consecutive FFPE tissue sections 1014:1045 consecutive FFPE tissue sections 1014:1045 METHODS AND RESULTS Our workflow presents a comprehensive list of instructions on how to (i) apply MALDI-MSI to spatially map the N-glycome across formalin-fixed paraffin-embedded (FFPE) clinical samples, (ii) structurally characterise N-glycans extracted from consecutive FFPE tissue sections by LC/MS/MS, and (iii) match relevant N-glycan masses from MALDI-MSI with confirmed N-glycan structures determined by LC/MS/MS. 28271569 2 1 theme novel 376:380 arg1 technique 392:400 a novel MALDI-MSI technique 374:400 a novel MALDI-MSI technique 374:400 In the last few years, MALDI-MSI of the N-glycome has emerged as a novel MALDI-MSI technique. 28271569 6 2 theme structural 1363:1372 arg1 detail 1374:1379 N-glycan structural detail 1354:1379 N-glycan structural detail 1354:1379 Furthermore, the method assigns N-glycan structural detail to the masses obtained in the MALDI-MS image. 28271569 1 3 theme past 296:299 arg1 decade 301:306 the past decade 292:306 the past decade 292:306 RATIONALE Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) of the proteome of a tissue has been an established technique for the past decade. 28271569 4 4 theme consecutive 1014:1024 arg1 sections 1038:1045 consecutive FFPE tissue sections 1014:1045 consecutive FFPE tissue sections 1014:1045 METHODS AND RESULTS Our workflow presents a comprehensive list of instructions on how to (i) apply MALDI-MSI to spatially map the N-glycome across formalin-fixed paraffin-embedded (FFPE) clinical samples, (ii) structurally characterise N-glycans extracted from consecutive FFPE tissue sections by LC/MS/MS, and (iii) match relevant N-glycan masses from MALDI-MSI with confirmed N-glycan structures determined by LC/MS/MS. 28271569 4 5 with MALDI-MSI 1106:1114 arg1 structures 1140:1149 confirmed N-glycan structures 1121:1149 confirmed N-glycan structures determined by LC/MS/MS 1121:1172 METHODS AND RESULTS Our workflow presents a comprehensive list of instructions on how to (i) apply MALDI-MSI to spatially map the N-glycome across formalin-fixed paraffin-embedded (FFPE) clinical samples, (ii) structurally characterise N-glycans extracted from consecutive FFPE tissue sections by LC/MS/MS, and (iii) match relevant N-glycan masses from MALDI-MSI with confirmed N-glycan structures determined by LC/MS/MS. 28271569 4 6 theme formalin-fixed 900:913 arg1 samples 949:955 formalin-fixed paraffin-embedded (FFPE) clinical samples 900:955 formalin-fixed paraffin-embedded (FFPE) clinical samples 900:955 METHODS AND RESULTS Our workflow presents a comprehensive list of instructions on how to (i) apply MALDI-MSI to spatially map the N-glycome across formalin-fixed paraffin-embedded (FFPE) clinical samples, (ii) structurally characterise N-glycans extracted from consecutive FFPE tissue sections by LC/MS/MS, and (iii) match relevant N-glycan masses from MALDI-MSI with confirmed N-glycan structures determined by LC/MS/MS. 28271569 4 7 theme N-glycan 1085:1092 arg1 masses 1094:1099 relevant N-glycan masses 1076:1099 relevant N-glycan masses from MALDI-MSI with confirmed N-glycan structures determined by LC/MS/MS 1076:1172 METHODS AND RESULTS Our workflow presents a comprehensive list of instructions on how to (i) apply MALDI-MSI to spatially map the N-glycome across formalin-fixed paraffin-embedded (FFPE) clinical samples, (ii) structurally characterise N-glycans extracted from consecutive FFPE tissue sections by LC/MS/MS, and (iii) match relevant N-glycan masses from MALDI-MSI with confirmed N-glycan structures determined by LC/MS/MS. 28271569 6 8 theme MALDI-MS 1411:1418 arg1 image 1420:1424 the MALDI-MS image 1407:1424 the MALDI-MS image 1407:1424 Furthermore, the method assigns N-glycan structural detail to the masses obtained in the MALDI-MS image. 28271569 4 9 theme paraffin-embedded 915:931 arg1 samples 949:955 formalin-fixed paraffin-embedded (FFPE) clinical samples 900:955 formalin-fixed paraffin-embedded (FFPE) clinical samples 900:955 METHODS AND RESULTS Our workflow presents a comprehensive list of instructions on how to (i) apply MALDI-MSI to spatially map the N-glycome across formalin-fixed paraffin-embedded (FFPE) clinical samples, (ii) structurally characterise N-glycans extracted from consecutive FFPE tissue sections by LC/MS/MS, and (iii) match relevant N-glycan masses from MALDI-MSI with confirmed N-glycan structures determined by LC/MS/MS. 28271569 3 10 theme tandem 593:598 arg1 LC/MS/MS 619:626 LC/MS/MS 619:626 LC/MS/MS 619:626 To assess the accuracy and clinical significance of the N-linked glycan spatial distribution, we have developed a method that utilises MALDI-MSI followed by liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS) in order to assign glycan structures to the differentiating MALDI-MSI glycan masses released from the tissue glycoproteins. 28271569 3 10 theme tandem 593:598 arg1 spectrometry 605:616 tandem mass spectrometry 593:616 tandem mass spectrometry (LC/MS/MS) 593:627 To assess the accuracy and clinical significance of the N-linked glycan spatial distribution, we have developed a method that utilises MALDI-MSI followed by liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS) in order to assign glycan structures to the differentiating MALDI-MSI glycan masses released from the tissue glycoproteins. 28271569 4 11 theme comprehensive 797:809 arg1 list 811:814 a comprehensive list 795:814 a comprehensive list of instructions 795:830 METHODS AND RESULTS Our workflow presents a comprehensive list of instructions on how to (i) apply MALDI-MSI to spatially map the N-glycome across formalin-fixed paraffin-embedded (FFPE) clinical samples, (ii) structurally characterise N-glycans extracted from consecutive FFPE tissue sections by LC/MS/MS, and (iii) match relevant N-glycan masses from MALDI-MSI with confirmed N-glycan structures determined by LC/MS/MS. 28271569 4 12 dep match 1070:1074 arg1 iii 1065:1067 iii 1065:1067 iii 1065:1067 METHODS AND RESULTS Our workflow presents a comprehensive list of instructions on how to (i) apply MALDI-MSI to spatially map the N-glycome across formalin-fixed paraffin-embedded (FFPE) clinical samples, (ii) structurally characterise N-glycans extracted from consecutive FFPE tissue sections by LC/MS/MS, and (iii) match relevant N-glycan masses from MALDI-MSI with confirmed N-glycan structures determined by LC/MS/MS. 28271569 2 13 theme few 321:323 arg1 years 325:329 the last few years 312:329 the last few years 312:329 In the last few years, MALDI-MSI of the N-glycome has emerged as a novel MALDI-MSI technique. 28271569 3 14 dep accuracy 417:424 arg1 the 413:415 the 413:415 the 413:415 To assess the accuracy and clinical significance of the N-linked glycan spatial distribution, we have developed a method that utilises MALDI-MSI followed by liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS) in order to assign glycan structures to the differentiating MALDI-MSI glycan masses released from the tissue glycoproteins. 28271569 2 15 theme last 316:319 arg1 years 325:329 the last few years 312:329 the last few years 312:329 In the last few years, MALDI-MSI of the N-glycome has emerged as a novel MALDI-MSI technique. 28271569 3 16 theme N-linked 459:466 arg1 distribution 483:494 the N-linked glycan spatial distribution 455:494 the N-linked glycan spatial distribution 455:494 To assess the accuracy and clinical significance of the N-linked glycan spatial distribution, we have developed a method that utilises MALDI-MSI followed by liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS) in order to assign glycan structures to the differentiating MALDI-MSI glycan masses released from the tissue glycoproteins. 28271569 4 17 dep paraffin-embedded 915:931 arg1 FFPE 934:937 FFPE 934:937 FFPE 934:937 METHODS AND RESULTS Our workflow presents a comprehensive list of instructions on how to (i) apply MALDI-MSI to spatially map the N-glycome across formalin-fixed paraffin-embedded (FFPE) clinical samples, (ii) structurally characterise N-glycans extracted from consecutive FFPE tissue sections by LC/MS/MS, and (iii) match relevant N-glycan masses from MALDI-MSI with confirmed N-glycan structures determined by LC/MS/MS. 28271569 3 18 theme liquid 560:565 arg1 chromatography 567:580 liquid chromatography 560:580 liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS) 560:627 To assess the accuracy and clinical significance of the N-linked glycan spatial distribution, we have developed a method that utilises MALDI-MSI followed by liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS) in order to assign glycan structures to the differentiating MALDI-MSI glycan masses released from the tissue glycoproteins. 28271569 4 19 theme relevant 1076:1083 arg1 masses 1094:1099 relevant N-glycan masses 1076:1099 relevant N-glycan masses from MALDI-MSI with confirmed N-glycan structures determined by LC/MS/MS 1076:1172 METHODS AND RESULTS Our workflow presents a comprehensive list of instructions on how to (i) apply MALDI-MSI to spatially map the N-glycome across formalin-fixed paraffin-embedded (FFPE) clinical samples, (ii) structurally characterise N-glycans extracted from consecutive FFPE tissue sections by LC/MS/MS, and (iii) match relevant N-glycan masses from MALDI-MSI with confirmed N-glycan structures determined by LC/MS/MS. 28271569 1 20 theme proteome 233:240 arg1 MALDI-MSI 215:223 MALDI-MSI 215:223 MALDI-MSI 215:223 RATIONALE Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) of the proteome of a tissue has been an established technique for the past decade. 28271569 1 20 theme proteome 233:240 arg1 imaging 206:212 RATIONALE Matrix-assisted laser desorption/ionization mass spectrometry imaging 134:212 RATIONALE Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) of the proteome of a tissue 134:252 RATIONALE Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) of the proteome of a tissue has been an established technique for the past decade. 28271569 1 20 theme proteome 233:240 arg1 technique 278:286 an established technique 263:286 an established technique for the past decade 263:306 RATIONALE Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) of the proteome of a tissue has been an established technique for the past decade. 28271569 0 21 theme matrix-assisted 9:23 arg1 spectrometry 58:69 N-Glycan matrix-assisted laser desorption/ionization mass spectrometry 0:69 N-Glycan matrix-assisted laser desorption/ionization mass spectrometry 0:69 N-Glycan matrix-assisted laser desorption/ionization mass spectrometry imaging protocol for formalin-fixed paraffin-embedded tissues. 28271569 3 22 link N-linked 459:466 arg1 distribution 483:494 the N-linked glycan spatial distribution 455:494 the N-linked glycan spatial distribution 455:494 To assess the accuracy and clinical significance of the N-linked glycan spatial distribution, we have developed a method that utilises MALDI-MSI followed by liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS) in order to assign glycan structures to the differentiating MALDI-MSI glycan masses released from the tissue glycoproteins. 28271569 3 23 theme mass 600:603 arg1 LC/MS/MS 619:626 LC/MS/MS 619:626 LC/MS/MS 619:626 To assess the accuracy and clinical significance of the N-linked glycan spatial distribution, we have developed a method that utilises MALDI-MSI followed by liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS) in order to assign glycan structures to the differentiating MALDI-MSI glycan masses released from the tissue glycoproteins. 28271569 3 23 theme mass 600:603 arg1 spectrometry 605:616 tandem mass spectrometry 593:616 tandem mass spectrometry (LC/MS/MS) 593:627 To assess the accuracy and clinical significance of the N-linked glycan spatial distribution, we have developed a method that utilises MALDI-MSI followed by liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS) in order to assign glycan structures to the differentiating MALDI-MSI glycan masses released from the tissue glycoproteins. 28271569 0 24 theme N-Glycan 0:7 arg1 spectrometry 58:69 N-Glycan matrix-assisted laser desorption/ionization mass spectrometry 0:69 N-Glycan matrix-assisted laser desorption/ionization mass spectrometry 0:69 N-Glycan matrix-assisted laser desorption/ionization mass spectrometry imaging protocol for formalin-fixed paraffin-embedded tissues. 28271569 3 25 theme glycan 699:704 arg1 masses 706:711 the differentiating MALDI-MSI glycan masses 669:711 the differentiating MALDI-MSI glycan masses released from the tissue glycoproteins 669:750 To assess the accuracy and clinical significance of the N-linked glycan spatial distribution, we have developed a method that utilises MALDI-MSI followed by liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS) in order to assign glycan structures to the differentiating MALDI-MSI glycan masses released from the tissue glycoproteins. 28271569 1 26 theme RATIONALE 134:142 arg1 spectrometry 193:204 RATIONALE Matrix-assisted laser desorption/ionization mass spectrometry 134:204 RATIONALE Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) of the proteome of a tissue 134:252 RATIONALE Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) of the proteome of a tissue has been an established technique for the past decade. 28271569 4 27 theme N-glycan 1131:1138 arg1 structures 1140:1149 confirmed N-glycan structures 1121:1149 confirmed N-glycan structures determined by LC/MS/MS 1121:1172 METHODS AND RESULTS Our workflow presents a comprehensive list of instructions on how to (i) apply MALDI-MSI to spatially map the N-glycome across formalin-fixed paraffin-embedded (FFPE) clinical samples, (ii) structurally characterise N-glycans extracted from consecutive FFPE tissue sections by LC/MS/MS, and (iii) match relevant N-glycan masses from MALDI-MSI with confirmed N-glycan structures determined by LC/MS/MS. 28271569 0 28 theme desorption/ionization 31:51 arg1 spectrometry 58:69 N-Glycan matrix-assisted laser desorption/ionization mass spectrometry 0:69 N-Glycan matrix-assisted laser desorption/ionization mass spectrometry 0:69 N-Glycan matrix-assisted laser desorption/ionization mass spectrometry imaging protocol for formalin-fixed paraffin-embedded tissues. 28271569 5 29 dep CONCLUSIONS 1175:1185 arg1 provides 1200:1207 provides 1200:1207 provides groups that are new to this technique with instructions how to establish N-glycan MALDI-MSI in their laboratory 1200:1319 CONCLUSIONS Our protocol provides groups that are new to this technique with instructions how to establish N-glycan MALDI-MSI in their laboratory. 28271569 1 30 theme Matrix-assisted 144:158 arg1 spectrometry 193:204 RATIONALE Matrix-assisted laser desorption/ionization mass spectrometry 134:204 RATIONALE Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) of the proteome of a tissue 134:252 RATIONALE Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) of the proteome of a tissue has been an established technique for the past decade. 28271569 4 31 theme confirmed 1121:1129 arg1 structures 1140:1149 confirmed N-glycan structures 1121:1149 confirmed N-glycan structures determined by LC/MS/MS 1121:1172 METHODS AND RESULTS Our workflow presents a comprehensive list of instructions on how to (i) apply MALDI-MSI to spatially map the N-glycome across formalin-fixed paraffin-embedded (FFPE) clinical samples, (ii) structurally characterise N-glycans extracted from consecutive FFPE tissue sections by LC/MS/MS, and (iii) match relevant N-glycan masses from MALDI-MSI with confirmed N-glycan structures determined by LC/MS/MS. 28271569 1 32 theme tissue 247:252 arg1 proteome 233:240 the proteome 229:240 the proteome of a tissue 229:252 RATIONALE Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) of the proteome of a tissue has been an established technique for the past decade. 28271569 0 33 theme laser 25:29 arg1 spectrometry 58:69 N-Glycan matrix-assisted laser desorption/ionization mass spectrometry 0:69 N-Glycan matrix-assisted laser desorption/ionization mass spectrometry 0:69 N-Glycan matrix-assisted laser desorption/ionization mass spectrometry imaging protocol for formalin-fixed paraffin-embedded tissues. 28271569 4 34 theme instructions 819:830 arg1 list 811:814 a comprehensive list 795:814 a comprehensive list of instructions 795:830 METHODS AND RESULTS Our workflow presents a comprehensive list of instructions on how to (i) apply MALDI-MSI to spatially map the N-glycome across formalin-fixed paraffin-embedded (FFPE) clinical samples, (ii) structurally characterise N-glycans extracted from consecutive FFPE tissue sections by LC/MS/MS, and (iii) match relevant N-glycan masses from MALDI-MSI with confirmed N-glycan structures determined by LC/MS/MS. 28271569 1 35 theme laser 160:164 arg1 spectrometry 193:204 RATIONALE Matrix-assisted laser desorption/ionization mass spectrometry 134:204 RATIONALE Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) of the proteome of a tissue 134:252 RATIONALE Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) of the proteome of a tissue has been an established technique for the past decade. 28271569 4 36 dep apply 846:850 arg1 i 843:843 i 843:843 i 843:843 METHODS AND RESULTS Our workflow presents a comprehensive list of instructions on how to (i) apply MALDI-MSI to spatially map the N-glycome across formalin-fixed paraffin-embedded (FFPE) clinical samples, (ii) structurally characterise N-glycans extracted from consecutive FFPE tissue sections by LC/MS/MS, and (iii) match relevant N-glycan masses from MALDI-MSI with confirmed N-glycan structures determined by LC/MS/MS. 28271569 3 37 theme clinical 430:437 arg1 significance 439:450 clinical significance 430:450 clinical significance 430:450 To assess the accuracy and clinical significance of the N-linked glycan spatial distribution, we have developed a method that utilises MALDI-MSI followed by liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS) in order to assign glycan structures to the differentiating MALDI-MSI glycan masses released from the tissue glycoproteins. 28271569 4 38 from MALDI-MSI 1106:1114 arg1 masses 1094:1099 relevant N-glycan masses 1076:1099 relevant N-glycan masses from MALDI-MSI with confirmed N-glycan structures determined by LC/MS/MS 1076:1172 METHODS AND RESULTS Our workflow presents a comprehensive list of instructions on how to (i) apply MALDI-MSI to spatially map the N-glycome across formalin-fixed paraffin-embedded (FFPE) clinical samples, (ii) structurally characterise N-glycans extracted from consecutive FFPE tissue sections by LC/MS/MS, and (iii) match relevant N-glycan masses from MALDI-MSI with confirmed N-glycan structures determined by LC/MS/MS. 28271569 3 39 theme differentiating 673:687 arg1 masses 706:711 the differentiating MALDI-MSI glycan masses 669:711 the differentiating MALDI-MSI glycan masses released from the tissue glycoproteins 669:750 To assess the accuracy and clinical significance of the N-linked glycan spatial distribution, we have developed a method that utilises MALDI-MSI followed by liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS) in order to assign glycan structures to the differentiating MALDI-MSI glycan masses released from the tissue glycoproteins. 28271569 3 40 theme spatial 475:481 arg1 distribution 483:494 the N-linked glycan spatial distribution 455:494 the N-linked glycan spatial distribution 455:494 To assess the accuracy and clinical significance of the N-linked glycan spatial distribution, we have developed a method that utilises MALDI-MSI followed by liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS) in order to assign glycan structures to the differentiating MALDI-MSI glycan masses released from the tissue glycoproteins. 28271569 0 41 theme mass 53:56 arg1 spectrometry 58:69 N-Glycan matrix-assisted laser desorption/ionization mass spectrometry 0:69 N-Glycan matrix-assisted laser desorption/ionization mass spectrometry 0:69 N-Glycan matrix-assisted laser desorption/ionization mass spectrometry imaging protocol for formalin-fixed paraffin-embedded tissues. 28271569 3 42 gly glycoproteins 738:750 arg1 glycoproteins 738:750 the tissue glycoproteins 727:750 the tissue glycoproteins 727:750 To assess the accuracy and clinical significance of the N-linked glycan spatial distribution, we have developed a method that utilises MALDI-MSI followed by liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS) in order to assign glycan structures to the differentiating MALDI-MSI glycan masses released from the tissue glycoproteins. 28271569 4 43 theme tissue 1031:1036 arg1 sections 1038:1045 consecutive FFPE tissue sections 1014:1045 consecutive FFPE tissue sections 1014:1045 METHODS AND RESULTS Our workflow presents a comprehensive list of instructions on how to (i) apply MALDI-MSI to spatially map the N-glycome across formalin-fixed paraffin-embedded (FFPE) clinical samples, (ii) structurally characterise N-glycans extracted from consecutive FFPE tissue sections by LC/MS/MS, and (iii) match relevant N-glycan masses from MALDI-MSI with confirmed N-glycan structures determined by LC/MS/MS. 28271569 3 44 theme distribution 483:494 arg1 accuracy 417:424 accuracy 417:424 accuracy 417:424 To assess the accuracy and clinical significance of the N-linked glycan spatial distribution, we have developed a method that utilises MALDI-MSI followed by liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS) in order to assign glycan structures to the differentiating MALDI-MSI glycan masses released from the tissue glycoproteins. 28271569 3 44 theme distribution 483:494 arg1 significance 439:450 clinical significance 430:450 clinical significance 430:450 To assess the accuracy and clinical significance of the N-linked glycan spatial distribution, we have developed a method that utilises MALDI-MSI followed by liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS) in order to assign glycan structures to the differentiating MALDI-MSI glycan masses released from the tissue glycoproteins. 28271569 4 45 dep characterise 976:987 arg1 ii 959:960 ii 959:960 ii 959:960 METHODS AND RESULTS Our workflow presents a comprehensive list of instructions on how to (i) apply MALDI-MSI to spatially map the N-glycome across formalin-fixed paraffin-embedded (FFPE) clinical samples, (ii) structurally characterise N-glycans extracted from consecutive FFPE tissue sections by LC/MS/MS, and (iii) match relevant N-glycan masses from MALDI-MSI with confirmed N-glycan structures determined by LC/MS/MS. 28271569 1 46 theme desorption/ionization 166:186 arg1 spectrometry 193:204 RATIONALE Matrix-assisted laser desorption/ionization mass spectrometry 134:204 RATIONALE Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) of the proteome of a tissue 134:252 RATIONALE Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) of the proteome of a tissue has been an established technique for the past decade. 28271569 6 47 theme N-glycan 1354:1361 arg1 detail 1374:1379 N-glycan structural detail 1354:1379 N-glycan structural detail 1354:1379 Furthermore, the method assigns N-glycan structural detail to the masses obtained in the MALDI-MS image. 28271569 1 48 theme mass 188:191 arg1 spectrometry 193:204 RATIONALE Matrix-assisted laser desorption/ionization mass spectrometry 134:204 RATIONALE Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) of the proteome of a tissue 134:252 RATIONALE Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) of the proteome of a tissue has been an established technique for the past decade. 28271569 4 49 theme clinical 940:947 arg1 samples 949:955 formalin-fixed paraffin-embedded (FFPE) clinical samples 900:955 formalin-fixed paraffin-embedded (FFPE) clinical samples 900:955 METHODS AND RESULTS Our workflow presents a comprehensive list of instructions on how to (i) apply MALDI-MSI to spatially map the N-glycome across formalin-fixed paraffin-embedded (FFPE) clinical samples, (ii) structurally characterise N-glycans extracted from consecutive FFPE tissue sections by LC/MS/MS, and (iii) match relevant N-glycan masses from MALDI-MSI with confirmed N-glycan structures determined by LC/MS/MS. 28271569 5 50 with technique 1237:1245 arg1 instructions 1252:1263 instructions 1252:1263 instructions 1252:1263 CONCLUSIONS Our protocol provides groups that are new to this technique with instructions how to establish N-glycan MALDI-MSI in their laboratory. 28271569 1 51 theme spectrometry 193:204 arg1 MALDI-MSI 215:223 MALDI-MSI 215:223 MALDI-MSI 215:223 RATIONALE Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) of the proteome of a tissue has been an established technique for the past decade. 28271569 1 51 theme spectrometry 193:204 arg1 imaging 206:212 RATIONALE Matrix-assisted laser desorption/ionization mass spectrometry imaging 134:212 RATIONALE Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) of the proteome of a tissue 134:252 RATIONALE Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) of the proteome of a tissue has been an established technique for the past decade. 28271569 1 51 theme spectrometry 193:204 arg1 technique 278:286 an established technique 263:286 an established technique for the past decade 263:306 RATIONALE Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) of the proteome of a tissue has been an established technique for the past decade. 28271569 0 52 dep formalin-fixed 92:105 arg1 paraffin-embedded 107:123 paraffin-embedded 107:123 paraffin-embedded 107:123 N-Glycan matrix-assisted laser desorption/ionization mass spectrometry imaging protocol for formalin-fixed paraffin-embedded tissues. 28271569 1 53 theme established 266:276 arg1 imaging 206:212 RATIONALE Matrix-assisted laser desorption/ionization mass spectrometry imaging 134:212 RATIONALE Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) of the proteome of a tissue 134:252 RATIONALE Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) of the proteome of a tissue has been an established technique for the past decade. 28271569 1 53 theme established 266:276 arg1 technique 278:286 an established technique 263:286 an established technique for the past decade 263:306 RATIONALE Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) of the proteome of a tissue has been an established technique for the past decade. 28271569 3 54 theme MALDI-MSI 689:697 arg1 masses 706:711 the differentiating MALDI-MSI glycan masses 669:711 the differentiating MALDI-MSI glycan masses released from the tissue glycoproteins 669:750 To assess the accuracy and clinical significance of the N-linked glycan spatial distribution, we have developed a method that utilises MALDI-MSI followed by liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS) in order to assign glycan structures to the differentiating MALDI-MSI glycan masses released from the tissue glycoproteins. 28271569 3 55 theme glycan 648:653 arg1 structures 655:664 glycan structures 648:664 glycan structures 648:664 To assess the accuracy and clinical significance of the N-linked glycan spatial distribution, we have developed a method that utilises MALDI-MSI followed by liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS) in order to assign glycan structures to the differentiating MALDI-MSI glycan masses released from the tissue glycoproteins. 28271569 2 56 theme N-glycome 349:357 arg1 MALDI-MSI 332:340 MALDI-MSI 332:340 MALDI-MSI of the N-glycome 332:357 In the last few years, MALDI-MSI of the N-glycome has emerged as a novel MALDI-MSI technique. 28271569 4 57 dep workflow 777:784 arg1 presents 786:793 presents 786:793 presents a comprehensive list of instructions on how to (i) apply MALDI-MSI to spatially map the N-glycome across formalin-fixed paraffin-embedded (FFPE) clinical samples, (ii) structurally characterise N-glycans extracted from consecutive FFPE tissue sections by LC/MS/MS, and (iii) match relevant N-glycan masses from MALDI-MSI with confirmed N-glycan structures determined by LC/MS/MS 786:1172 METHODS AND RESULTS Our workflow presents a comprehensive list of instructions on how to (i) apply MALDI-MSI to spatially map the N-glycome across formalin-fixed paraffin-embedded (FFPE) clinical samples, (ii) structurally characterise N-glycans extracted from consecutive FFPE tissue sections by LC/MS/MS, and (iii) match relevant N-glycan masses from MALDI-MSI with confirmed N-glycan structures determined by LC/MS/MS. 28271569 0 58 theme formalin-fixed 92:105 arg1 tissues 125:131 formalin-fixed paraffin-embedded tissues 92:131 formalin-fixed paraffin-embedded tissues 92:131 N-Glycan matrix-assisted laser desorption/ionization mass spectrometry imaging protocol for formalin-fixed paraffin-embedded tissues. 28271569 3 59 attach released 713:720 arg2 masses 706:711 the differentiating MALDI-MSI glycan masses 669:711 the differentiating MALDI-MSI glycan masses released from the tissue glycoproteins 669:750 To assess the accuracy and clinical significance of the N-linked glycan spatial distribution, we have developed a method that utilises MALDI-MSI followed by liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS) in order to assign glycan structures to the differentiating MALDI-MSI glycan masses released from the tissue glycoproteins. 28271569 3 59 attach released 713:720 arg1 glycoproteins 738:750 the tissue glycoproteins 727:750 the tissue glycoproteins 727:750 To assess the accuracy and clinical significance of the N-linked glycan spatial distribution, we have developed a method that utilises MALDI-MSI followed by liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS) in order to assign glycan structures to the differentiating MALDI-MSI glycan masses released from the tissue glycoproteins. 28271569 7 60 dep & 1455:1455 arg1 Sons 1457:1460 Sons 1457:1460 Sons 1457:1460 Copyright © 2017 John Wiley & Sons, Ltd. 28271569 3 61 theme glycan 468:473 arg1 distribution 483:494 the N-linked glycan spatial distribution 455:494 the N-linked glycan spatial distribution 455:494 To assess the accuracy and clinical significance of the N-linked glycan spatial distribution, we have developed a method that utilises MALDI-MSI followed by liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS) in order to assign glycan structures to the differentiating MALDI-MSI glycan masses released from the tissue glycoproteins. 28271569 3 62 theme tissue 731:736 arg1 glycoproteins 738:750 the tissue glycoproteins 727:750 the tissue glycoproteins 727:750 To assess the accuracy and clinical significance of the N-linked glycan spatial distribution, we have developed a method that utilises MALDI-MSI followed by liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS) in order to assign glycan structures to the differentiating MALDI-MSI glycan masses released from the tissue glycoproteins. 28271569 2 63 theme MALDI-MSI 382:390 arg1 technique 392:400 a novel MALDI-MSI technique 374:400 a novel MALDI-MSI technique 374:400 In the last few years, MALDI-MSI of the N-glycome has emerged as a novel MALDI-MSI technique. 28271569 5 64 theme N-glycan 1282:1289 arg1 MALDI-MSI 1291:1299 N-glycan MALDI-MSI 1282:1299 N-glycan MALDI-MSI 1282:1299 CONCLUSIONS Our protocol provides groups that are new to this technique with instructions how to establish N-glycan MALDI-MSI in their laboratory. 27809484 6 0 from glycoproteins 887:899 arg1 branching 951:959 N-linked glycan branching 935:959 N-linked glycan branching 935:959 We demonstrated the efficacy of the method to characterize differences between glycoproteins in their sialic acid linkages and N-linked glycan branching, and we validated the assignments by comparing results from mass spectrometry and chromatography. 27809484 6 0 from glycoproteins 887:899 arg1 linkages 922:929 their sialic acid linkages 904:929 their sialic acid linkages 904:929 We demonstrated the efficacy of the method to characterize differences between glycoproteins in their sialic acid linkages and N-linked glycan branching, and we validated the assignments by comparing results from mass spectrometry and chromatography. 27809484 10 1 theme on-chip 1451:1457 arg1 GMAP 1459:1462 on-chip GMAP 1451:1462 on-chip GMAP 1451:1462 The on-chip glycan modification and probing (on-chip GMAP) method provides a platform for analyzing protein glycosylation in clinical specimens and could complement the existing toolkit for studying glycosylation in disease. 27809484 10 1 theme on-chip 1451:1457 arg1 probing 1442:1448 probing 1442:1448 probing (on-chip GMAP) 1442:1463 The on-chip glycan modification and probing (on-chip GMAP) method provides a platform for analyzing protein glycosylation in clinical specimens and could complement the existing toolkit for studying glycosylation in disease. 27809484 10 2 theme clinical 1531:1538 arg1 specimens 1540:1548 clinical specimens 1531:1548 clinical specimens 1531:1548 The on-chip glycan modification and probing (on-chip GMAP) method provides a platform for analyzing protein glycosylation in clinical specimens and could complement the existing toolkit for studying glycosylation in disease. 27809484 4 3 theme glycan-binding 655:668 arg1 reagents 670:677 glycan-binding reagents 655:677 glycan-binding reagents 655:677 We treat proteins that were captured or directly spotted in small microarrays (2.2 mm × 2.2 mm) with exoglycosidases to successively expose underlying features, and then we probe the native or exposed features using a panel of lectins or glycan-binding reagents. 27809484 6 4 gly glycoproteins 887:899 arg1 glycoproteins 887:899 glycoproteins 887:899 glycoproteins in their sialic acid linkages and N-linked glycan branching 887:959 We demonstrated the efficacy of the method to characterize differences between glycoproteins in their sialic acid linkages and N-linked glycan branching, and we validated the assignments by comparing results from mass spectrometry and chromatography. 27809484 4 5 theme underlying 557:566 arg1 features 568:575 underlying features 557:575 underlying features 557:575 We treat proteins that were captured or directly spotted in small microarrays (2.2 mm × 2.2 mm) with exoglycosidases to successively expose underlying features, and then we probe the native or exposed features using a panel of lectins or glycan-binding reagents. 27809484 8 6 theme plasma 1247:1252 arg1 μL 1237:1238 only 20 μL 1229:1238 only 20 μL of the plasma 1229:1252 The method also proved effective for analyzing the glycosylation of a cancer biomarker in human plasma, MUC5AC, using only 20 μL of the plasma. 27809484 4 7 theme mm 500:501 arg1 mm 509:510 2.2 mm × 2.2 mm 496:510 2.2 mm × 2.2 mm 496:510 We treat proteins that were captured or directly spotted in small microarrays (2.2 mm × 2.2 mm) with exoglycosidases to successively expose underlying features, and then we probe the native or exposed features using a panel of lectins or glycan-binding reagents. 27809484 4 7 theme mm 500:501 arg1 microarrays 483:493 small microarrays 477:493 small microarrays (2.2 mm × 2.2 mm) with exoglycosidases to successively expose underlying features 477:575 We treat proteins that were captured or directly spotted in small microarrays (2.2 mm × 2.2 mm) with exoglycosidases to successively expose underlying features, and then we probe the native or exposed features using a panel of lectins or glycan-binding reagents. 27809484 9 8 contain had 1372:1374 arg2 linkage 1382:1388 a 2,6 linkage 1376:1388 a 2,6 linkage of sialic acid 1376:1403 A glycan on MUC5AC that is associated with cancer had mostly 2,3-linked sialic acid, whereas other glycans on MUC5AC had a 2,6 linkage of sialic acid. 27809484 9 8 contain had 1372:1374 arg1 glycans 1354:1360 other glycans 1348:1360 other glycans on MUC5AC 1348:1370 A glycan on MUC5AC that is associated with cancer had mostly 2,3-linked sialic acid, whereas other glycans on MUC5AC had a 2,6 linkage of sialic acid. 27809484 7 9 theme used 1081:1084 arg1 on-chip 1086:1092 protein used on-chip 1073:1092 protein used on-chip 1073:1092 The amount of protein used on-chip was about 11 ng. 27809484 5 10 located present 785:791 arg1 sample 800:805 the sample 796:805 the sample 796:805 We developed an algorithm to interpret the data and provide predictions about the glycan motifs that are present in the sample. 27809484 5 10 located present 785:791 arg2 present 785:791 present 785:791 present 785:791 We developed an algorithm to interpret the data and provide predictions about the glycan motifs that are present in the sample. 27809484 5 10 located present 785:791 arg2 motifs 769:774 the glycan motifs 758:774 the glycan motifs that are present in the sample 758:805 We developed an algorithm to interpret the data and provide predictions about the glycan motifs that are present in the sample. 27809484 8 11 from biomarker 1188:1196 arg1 plasma 1207:1212 human plasma 1201:1212 human plasma 1201:1212 The method also proved effective for analyzing the glycosylation of a cancer biomarker in human plasma, MUC5AC, using only 20 μL of the plasma. 27809484 10 12 theme existing 1575:1582 arg1 toolkit 1584:1590 the existing toolkit 1571:1590 the existing toolkit for studying glycosylation in disease 1571:1628 The on-chip glycan modification and probing (on-chip GMAP) method provides a platform for analyzing protein glycosylation in clinical specimens and could complement the existing toolkit for studying glycosylation in disease. 27809484 9 13 theme other 1348:1352 arg1 glycans 1354:1360 other glycans 1348:1360 other glycans on MUC5AC 1348:1370 A glycan on MUC5AC that is associated with cancer had mostly 2,3-linked sialic acid, whereas other glycans on MUC5AC had a 2,6 linkage of sialic acid. 27809484 10 14 theme protein 1506:1512 arg1 glycosylation 1514:1526 protein glycosylation 1506:1526 protein glycosylation 1506:1526 The on-chip glycan modification and probing (on-chip GMAP) method provides a platform for analyzing protein glycosylation in clinical specimens and could complement the existing toolkit for studying glycosylation in disease. 27809484 2 15 theme Many 164:167 arg1 studies 169:175 Many studies 164:175 Many studies of glycans 164:186 Many studies of glycans rely on clinical specimens, but the low amount of sample available for some specimens limits the experimental options. 27809484 7 16 theme on-chip 1086:1092 arg1 on-chip 1086:1092 protein used on-chip 1073:1092 protein used on-chip 1073:1092 The amount of protein used on-chip was about 11 ng. 27809484 7 16 theme on-chip 1086:1092 arg1 amount 1063:1068 The amount 1059:1068 The amount of protein used on-chip 1059:1092 The amount of protein used on-chip was about 11 ng. 27809484 7 16 theme on-chip 1086:1092 arg1 ng 1107:1108 about 11 ng 1098:1108 about 11 ng 1098:1108 The amount of protein used on-chip was about 11 ng. 27809484 5 17 attach present 785:791 arg1 sample 800:805 the sample 796:805 the sample 796:805 We developed an algorithm to interpret the data and provide predictions about the glycan motifs that are present in the sample. 27809484 5 17 attach present 785:791 arg2 present 785:791 present 785:791 present 785:791 We developed an algorithm to interpret the data and provide predictions about the glycan motifs that are present in the sample. 27809484 5 17 attach present 785:791 arg2 motifs 769:774 the glycan motifs 758:774 the glycan motifs that are present in the sample 758:805 We developed an algorithm to interpret the data and provide predictions about the glycan motifs that are present in the sample. 27809484 9 18 theme 2,6 1378:1380 arg1 linkage 1382:1388 a 2,6 linkage 1376:1388 a 2,6 linkage of sialic acid 1376:1403 A glycan on MUC5AC that is associated with cancer had mostly 2,3-linked sialic acid, whereas other glycans on MUC5AC had a 2,6 linkage of sialic acid. 27809484 5 19 from present 785:791 arg1 sample 800:805 the sample 796:805 the sample 796:805 We developed an algorithm to interpret the data and provide predictions about the glycan motifs that are present in the sample. 27809484 6 20 from chromatography 1043:1056 arg1 results 1008:1014 results 1008:1014 results from mass spectrometry and chromatography 1008:1056 We demonstrated the efficacy of the method to characterize differences between glycoproteins in their sialic acid linkages and N-linked glycan branching, and we validated the assignments by comparing results from mass spectrometry and chromatography. 27809484 8 21 theme human 1201:1205 arg1 plasma 1207:1212 human plasma 1201:1212 human plasma 1201:1212 The method also proved effective for analyzing the glycosylation of a cancer biomarker in human plasma, MUC5AC, using only 20 μL of the plasma. 27809484 8 22 theme cancer 1181:1186 arg1 MUC5AC 1215:1220 MUC5AC 1215:1220 MUC5AC 1215:1220 The method also proved effective for analyzing the glycosylation of a cancer biomarker in human plasma, MUC5AC, using only 20 μL of the plasma. 27809484 8 22 theme cancer 1181:1186 arg1 biomarker 1188:1196 a cancer biomarker 1179:1196 a cancer biomarker in human plasma 1179:1212 The method also proved effective for analyzing the glycosylation of a cancer biomarker in human plasma, MUC5AC, using only 20 μL of the plasma. 27809484 4 23 theme small 477:481 arg1 mm 509:510 2.2 mm × 2.2 mm 496:510 2.2 mm × 2.2 mm 496:510 We treat proteins that were captured or directly spotted in small microarrays (2.2 mm × 2.2 mm) with exoglycosidases to successively expose underlying features, and then we probe the native or exposed features using a panel of lectins or glycan-binding reagents. 27809484 4 23 theme small 477:481 arg1 microarrays 483:493 small microarrays 477:493 small microarrays (2.2 mm × 2.2 mm) with exoglycosidases to successively expose underlying features 477:575 We treat proteins that were captured or directly spotted in small microarrays (2.2 mm × 2.2 mm) with exoglycosidases to successively expose underlying features, and then we probe the native or exposed features using a panel of lectins or glycan-binding reagents. 27809484 8 24 dep MUC5AC 1215:1220 arg1 using 1223:1227 using 1223:1227 using only 20 μL of the plasma 1223:1252 The method also proved effective for analyzing the glycosylation of a cancer biomarker in human plasma, MUC5AC, using only 20 μL of the plasma. 27809484 0 25 theme Protein 15:21 arg1 Glycosylation 23:35 Protein Glycosylation 15:35 Protein Glycosylation 15:35 Characterizing Protein Glycosylation through On-Chip Glycan Modification and Probing. 27809484 10 26 gly glycosylation 1514:1526 arg1 specimens 1540:1548 clinical specimens 1531:1548 clinical specimens 1531:1548 The on-chip glycan modification and probing (on-chip GMAP) method provides a platform for analyzing protein glycosylation in clinical specimens and could complement the existing toolkit for studying glycosylation in disease. 27809484 6 27 theme method 844:849 arg1 efficacy 828:835 the efficacy 824:835 the efficacy of the method to characterize differences between glycoproteins in their sialic acid linkages and N-linked glycan branching 824:959 We demonstrated the efficacy of the method to characterize differences between glycoproteins in their sialic acid linkages and N-linked glycan branching, and we validated the assignments by comparing results from mass spectrometry and chromatography. 27809484 9 28 from glycan 1257:1262 arg1 MUC5AC 1267:1272 MUC5AC 1267:1272 MUC5AC 1267:1272 A glycan on MUC5AC that is associated with cancer had mostly 2,3-linked sialic acid, whereas other glycans on MUC5AC had a 2,6 linkage of sialic acid. 27809484 6 29 theme glycan 944:949 arg1 branching 951:959 N-linked glycan branching 935:959 N-linked glycan branching 935:959 We demonstrated the efficacy of the method to characterize differences between glycoproteins in their sialic acid linkages and N-linked glycan branching, and we validated the assignments by comparing results from mass spectrometry and chromatography. 27809484 10 30 gly glycosylation 1605:1617 arg1 disease 1622:1628 disease 1622:1628 disease 1622:1628 The on-chip glycan modification and probing (on-chip GMAP) method provides a platform for analyzing protein glycosylation in clinical specimens and could complement the existing toolkit for studying glycosylation in disease. 27809484 3 31 theme protein 360:366 arg1 glycosylation 368:380 protein glycosylation 360:380 protein glycosylation 360:380 Here we present a method to obtain information about protein glycosylation using a minimal amount of protein. 27809484 6 32 theme N-linked 935:942 arg1 branching 951:959 N-linked glycan branching 935:959 N-linked glycan branching 935:959 We demonstrated the efficacy of the method to characterize differences between glycoproteins in their sialic acid linkages and N-linked glycan branching, and we validated the assignments by comparing results from mass spectrometry and chromatography. 27809484 10 33 theme on-chip 1410:1416 arg1 modification 1425:1436 on-chip glycan modification 1410:1436 on-chip glycan modification 1410:1436 The on-chip glycan modification and probing (on-chip GMAP) method provides a platform for analyzing protein glycosylation in clinical specimens and could complement the existing toolkit for studying glycosylation in disease. 27809484 8 34 gly glycosylation 1162:1174 arg1 MUC5AC 1215:1220 MUC5AC 1215:1220 MUC5AC 1215:1220 The method also proved effective for analyzing the glycosylation of a cancer biomarker in human plasma, MUC5AC, using only 20 μL of the plasma. 27809484 8 34 gly glycosylation 1162:1174 arg1 biomarker 1188:1196 a cancer biomarker 1179:1196 a cancer biomarker in human plasma 1179:1212 The method also proved effective for analyzing the glycosylation of a cancer biomarker in human plasma, MUC5AC, using only 20 μL of the plasma. 27809484 1 35 theme protein 110:116 arg1 biology 118:124 protein biology 110:124 protein biology 110:124 Glycans are critical to protein biology and are useful as disease biomarkers. 27809484 4 36 theme native 600:605 arg1 features 618:625 the native or exposed features 596:625 the native or exposed features using a panel of lectins or glycan-binding reagents 596:677 We treat proteins that were captured or directly spotted in small microarrays (2.2 mm × 2.2 mm) with exoglycosidases to successively expose underlying features, and then we probe the native or exposed features using a panel of lectins or glycan-binding reagents. 27809484 9 37 from glycans 1354:1360 arg1 MUC5AC 1365:1370 MUC5AC 1365:1370 MUC5AC 1365:1370 A glycan on MUC5AC that is associated with cancer had mostly 2,3-linked sialic acid, whereas other glycans on MUC5AC had a 2,6 linkage of sialic acid. 27809484 2 38 theme experimental 285:296 arg1 options 298:304 the experimental options 281:304 the experimental options 281:304 Many studies of glycans rely on clinical specimens, but the low amount of sample available for some specimens limits the experimental options. 27809484 1 39 theme disease 144:150 arg1 biomarkers 152:161 disease biomarkers 144:161 disease biomarkers 144:161 Glycans are critical to protein biology and are useful as disease biomarkers. 27809484 0 40 theme Glycan 53:58 arg1 Modification 60:71 On-Chip Glycan Modification 45:71 On-Chip Glycan Modification 45:71 Characterizing Protein Glycosylation through On-Chip Glycan Modification and Probing. 27809484 2 41 theme glycans 180:186 arg1 studies 169:175 Many studies 164:175 Many studies of glycans 164:186 Many studies of glycans rely on clinical specimens, but the low amount of sample available for some specimens limits the experimental options. 27809484 4 42 theme exposed 610:616 arg1 features 618:625 the native or exposed features 596:625 the native or exposed features using a panel of lectins or glycan-binding reagents 596:677 We treat proteins that were captured or directly spotted in small microarrays (2.2 mm × 2.2 mm) with exoglycosidases to successively expose underlying features, and then we probe the native or exposed features using a panel of lectins or glycan-binding reagents. 27809484 0 43 theme On-Chip 45:51 arg1 Modification 60:71 On-Chip Glycan Modification 45:71 On-Chip Glycan Modification 45:71 Characterizing Protein Glycosylation through On-Chip Glycan Modification and Probing. 27809484 6 44 theme acid 917:920 arg1 linkages 922:929 their sialic acid linkages 904:929 their sialic acid linkages 904:929 We demonstrated the efficacy of the method to characterize differences between glycoproteins in their sialic acid linkages and N-linked glycan branching, and we validated the assignments by comparing results from mass spectrometry and chromatography. 27809484 3 45 theme protein 408:414 arg1 amount 398:403 a minimal amount 388:403 a minimal amount of protein 388:414 Here we present a method to obtain information about protein glycosylation using a minimal amount of protein. 27809484 3 45 theme protein 408:414 arg1 protein 408:414 protein 408:414 protein 408:414 Here we present a method to obtain information about protein glycosylation using a minimal amount of protein. 27809484 2 46 theme low 224:226 arg1 sample 238:243 sample 238:243 sample available for some specimens 238:272 Many studies of glycans rely on clinical specimens, but the low amount of sample available for some specimens limits the experimental options. 27809484 2 46 theme low 224:226 arg1 amount 228:233 the low amount 220:233 the low amount of sample available for some specimens 220:272 Many studies of glycans rely on clinical specimens, but the low amount of sample available for some specimens limits the experimental options. 27809484 5 47 from sample 800:805 arg1 motifs 769:774 the glycan motifs 758:774 the glycan motifs that are present in the sample 758:805 We developed an algorithm to interpret the data and provide predictions about the glycan motifs that are present in the sample. 27809484 5 47 from sample 800:805 arg1 present 785:791 present 785:791 present 785:791 We developed an algorithm to interpret the data and provide predictions about the glycan motifs that are present in the sample. 27809484 9 48 theme sialic 1393:1398 arg1 acid 1400:1403 sialic acid 1393:1403 sialic acid 1393:1403 A glycan on MUC5AC that is associated with cancer had mostly 2,3-linked sialic acid, whereas other glycans on MUC5AC had a 2,6 linkage of sialic acid. 27809484 3 49 theme minimal 390:396 arg1 amount 398:403 a minimal amount 388:403 a minimal amount of protein 388:414 Here we present a method to obtain information about protein glycosylation using a minimal amount of protein. 27809484 3 49 theme minimal 390:396 arg1 protein 408:414 protein 408:414 protein 408:414 Here we present a method to obtain information about protein glycosylation using a minimal amount of protein. 27809484 4 50 theme × 503:503 arg1 mm 509:510 2.2 mm × 2.2 mm 496:510 2.2 mm × 2.2 mm 496:510 We treat proteins that were captured or directly spotted in small microarrays (2.2 mm × 2.2 mm) with exoglycosidases to successively expose underlying features, and then we probe the native or exposed features using a panel of lectins or glycan-binding reagents. 27809484 4 50 theme × 503:503 arg1 microarrays 483:493 small microarrays 477:493 small microarrays (2.2 mm × 2.2 mm) with exoglycosidases to successively expose underlying features 477:575 We treat proteins that were captured or directly spotted in small microarrays (2.2 mm × 2.2 mm) with exoglycosidases to successively expose underlying features, and then we probe the native or exposed features using a panel of lectins or glycan-binding reagents. 27809484 10 51 theme probing 1442:1448 arg1 method 1465:1470 The on-chip glycan modification and probing (on-chip GMAP) method 1406:1470 The on-chip glycan modification and probing (on-chip GMAP) method 1406:1470 The on-chip glycan modification and probing (on-chip GMAP) method provides a platform for analyzing protein glycosylation in clinical specimens and could complement the existing toolkit for studying glycosylation in disease. 27809484 9 52 dep 2,3-linked 1316:1325 arg1 whereas 1340:1346 whereas 1340:1346 whereas 1340:1346 A glycan on MUC5AC that is associated with cancer had mostly 2,3-linked sialic acid, whereas other glycans on MUC5AC had a 2,6 linkage of sialic acid. 27809484 8 53 from plasma 1207:1212 arg1 glycosylation 1162:1174 the glycosylation 1158:1174 the glycosylation of a cancer biomarker in human plasma, MUC5AC, using only 20 μL of the plasma 1158:1252 The method also proved effective for analyzing the glycosylation of a cancer biomarker in human plasma, MUC5AC, using only 20 μL of the plasma. 27809484 9 54 theme acid 1400:1403 arg1 linkage 1382:1388 a 2,6 linkage 1376:1388 a 2,6 linkage of sialic acid 1376:1403 A glycan on MUC5AC that is associated with cancer had mostly 2,3-linked sialic acid, whereas other glycans on MUC5AC had a 2,6 linkage of sialic acid. 27809484 5 55 theme glycan 762:767 arg1 motifs 769:774 the glycan motifs 758:774 the glycan motifs that are present in the sample 758:805 We developed an algorithm to interpret the data and provide predictions about the glycan motifs that are present in the sample. 27809484 5 55 theme glycan 762:767 arg1 present 785:791 present 785:791 present 785:791 We developed an algorithm to interpret the data and provide predictions about the glycan motifs that are present in the sample. 27809484 6 56 link N-linked 935:942 arg1 branching 951:959 N-linked glycan branching 935:959 N-linked glycan branching 935:959 We demonstrated the efficacy of the method to characterize differences between glycoproteins in their sialic acid linkages and N-linked glycan branching, and we validated the assignments by comparing results from mass spectrometry and chromatography. 27809484 4 57 theme reagents 670:677 arg1 panel 635:639 a panel 633:639 a panel of lectins or glycan-binding reagents 633:677 We treat proteins that were captured or directly spotted in small microarrays (2.2 mm × 2.2 mm) with exoglycosidases to successively expose underlying features, and then we probe the native or exposed features using a panel of lectins or glycan-binding reagents. 27809484 10 58 theme modification 1425:1436 arg1 method 1465:1470 The on-chip glycan modification and probing (on-chip GMAP) method 1406:1470 The on-chip glycan modification and probing (on-chip GMAP) method 1406:1470 The on-chip glycan modification and probing (on-chip GMAP) method provides a platform for analyzing protein glycosylation in clinical specimens and could complement the existing toolkit for studying glycosylation in disease. 27809484 6 59 from spectrometry 1026:1037 arg1 results 1008:1014 results 1008:1014 results from mass spectrometry and chromatography 1008:1056 We demonstrated the efficacy of the method to characterize differences between glycoproteins in their sialic acid linkages and N-linked glycan branching, and we validated the assignments by comparing results from mass spectrometry and chromatography. 27809484 10 60 theme glycan 1418:1423 arg1 modification 1425:1436 on-chip glycan modification 1410:1436 on-chip glycan modification 1410:1436 The on-chip glycan modification and probing (on-chip GMAP) method provides a platform for analyzing protein glycosylation in clinical specimens and could complement the existing toolkit for studying glycosylation in disease. 27809484 2 61 theme clinical 196:203 arg1 specimens 205:213 clinical specimens 196:213 clinical specimens 196:213 Many studies of glycans rely on clinical specimens, but the low amount of sample available for some specimens limits the experimental options. 27809484 2 62 theme available 245:253 arg1 sample 238:243 sample 238:243 sample available for some specimens 238:272 Many studies of glycans rely on clinical specimens, but the low amount of sample available for some specimens limits the experimental options. 27809484 4 63 with microarrays 483:493 arg1 exoglycosidases 518:532 exoglycosidases 518:532 exoglycosidases to successively expose underlying features 518:575 We treat proteins that were captured or directly spotted in small microarrays (2.2 mm × 2.2 mm) with exoglycosidases to successively expose underlying features, and then we probe the native or exposed features using a panel of lectins or glycan-binding reagents. 27809484 2 64 theme sample 238:243 arg1 sample 238:243 sample 238:243 sample available for some specimens 238:272 Many studies of glycans rely on clinical specimens, but the low amount of sample available for some specimens limits the experimental options. 27809484 2 64 theme sample 238:243 arg1 amount 228:233 the low amount 220:233 the low amount of sample available for some specimens 220:272 Many studies of glycans rely on clinical specimens, but the low amount of sample available for some specimens limits the experimental options. 27809484 6 65 theme mass 1021:1024 arg1 spectrometry 1026:1037 mass spectrometry 1021:1037 mass spectrometry 1021:1037 We demonstrated the efficacy of the method to characterize differences between glycoproteins in their sialic acid linkages and N-linked glycan branching, and we validated the assignments by comparing results from mass spectrometry and chromatography. 27809484 4 66 theme lectins 644:650 arg1 panel 635:639 a panel 633:639 a panel of lectins or glycan-binding reagents 633:677 We treat proteins that were captured or directly spotted in small microarrays (2.2 mm × 2.2 mm) with exoglycosidases to successively expose underlying features, and then we probe the native or exposed features using a panel of lectins or glycan-binding reagents. 27809484 9 67 theme sialic 1327:1332 arg1 acid 1334:1337 sialic acid 1327:1337 sialic acid 1327:1337 A glycan on MUC5AC that is associated with cancer had mostly 2,3-linked sialic acid, whereas other glycans on MUC5AC had a 2,6 linkage of sialic acid. 27809484 8 68 theme biomarker 1188:1196 arg1 glycosylation 1162:1174 the glycosylation 1158:1174 the glycosylation of a cancer biomarker in human plasma, MUC5AC, using only 20 μL of the plasma 1158:1252 The method also proved effective for analyzing the glycosylation of a cancer biomarker in human plasma, MUC5AC, using only 20 μL of the plasma. 27809484 8 69 from glycosylation 1162:1174 arg1 plasma 1207:1212 human plasma 1201:1212 human plasma 1201:1212 The method also proved effective for analyzing the glycosylation of a cancer biomarker in human plasma, MUC5AC, using only 20 μL of the plasma. 27809484 10 70 from glycosylation 1605:1617 arg1 disease 1622:1628 disease 1622:1628 disease 1622:1628 The on-chip glycan modification and probing (on-chip GMAP) method provides a platform for analyzing protein glycosylation in clinical specimens and could complement the existing toolkit for studying glycosylation in disease. 27809484 7 71 dep used 1081:1084 arg1 protein 1073:1079 protein 1073:1079 protein 1073:1079 The amount of protein used on-chip was about 11 ng. 27809484 6 72 theme sialic 910:915 arg1 linkages 922:929 their sialic acid linkages 904:929 their sialic acid linkages 904:929 We demonstrated the efficacy of the method to characterize differences between glycoproteins in their sialic acid linkages and N-linked glycan branching, and we validated the assignments by comparing results from mass spectrometry and chromatography. 27569060 7 0 theme hepatocyte-like 1264:1278 arg1 cells 1280:1284 iPSC-derived hepatocyte-like cells 1251:1284 iPSC-derived hepatocyte-like cells 1251:1284 In conclusion, we report an extensive catalog of cell-surface N-linked glycoproteins expressed in primary hepatocytes and identify cell-surface proteins that facilitate the purification of homogeneous populations of iPSC-derived hepatocyte-like cells. 27569060 6 1 theme stem 1002:1005 arg1 cell 1007:1010 a pluripotent stem cell 988:1010 a pluripotent stem cell network 988:1018 Moreover, transcriptome analyses revealed that cells expressing the liver gene regulatory network were enriched while cells expressing a pluripotent stem cell network were depleted. 27569060 1 2 link iPSC-derived 188:199 arg1 cells 217:221 iPSC-derived hepatocyte-like cells 188:221 iPSC-derived hepatocyte-like cells from different liver disease patients 188:259 When comparing hepatic phenotypes between iPSC-derived hepatocyte-like cells from different liver disease patients, cell heterogeneity can confound interpretation. 27569060 4 3 theme iPSCs 586:590 arg1 differentiation 567:581 the differentiation 563:581 the differentiation of iPSCs 563:590 Analyses of the expression profiles during the differentiation of iPSCs revealed that SLC10A1, CLRN3, and AADAC were highly enriched during the final stages of hepatocyte differentiation. 27569060 7 4 theme cells 1280:1284 arg1 populations 1236:1246 homogeneous populations 1224:1246 homogeneous populations of iPSC-derived hepatocyte-like cells 1224:1284 In conclusion, we report an extensive catalog of cell-surface N-linked glycoproteins expressed in primary hepatocytes and identify cell-surface proteins that facilitate the purification of homogeneous populations of iPSC-derived hepatocyte-like cells. 27569060 1 5 theme iPSC-derived 188:199 arg1 cells 217:221 iPSC-derived hepatocyte-like cells 188:221 iPSC-derived hepatocyte-like cells from different liver disease patients 188:259 When comparing hepatic phenotypes between iPSC-derived hepatocyte-like cells from different liver disease patients, cell heterogeneity can confound interpretation. 27569060 6 6 theme cell 1007:1010 arg1 network 1012:1018 a pluripotent stem cell network 988:1018 a pluripotent stem cell network 988:1018 Moreover, transcriptome analyses revealed that cells expressing the liver gene regulatory network were enriched while cells expressing a pluripotent stem cell network were depleted. 27569060 5 7 theme hepatocyte-like 729:743 arg1 cells 745:749 hepatocyte-like cells 729:749 hepatocyte-like cells expressing SLC10A1, CLRN3, or AADAC 729:785 FACS purification of hepatocyte-like cells expressing SLC10A1, CLRN3, or AADAC demonstrated enrichment of cells with hepatocyte characteristics. 27569060 7 8 theme extensive 1063:1071 arg1 catalog 1073:1079 an extensive catalog 1060:1079 an extensive catalog of cell-surface N-linked glycoproteins expressed in primary hepatocytes 1060:1151 In conclusion, we report an extensive catalog of cell-surface N-linked glycoproteins expressed in primary hepatocytes and identify cell-surface proteins that facilitate the purification of homogeneous populations of iPSC-derived hepatocyte-like cells. 27569060 0 9 theme Homogeneous 94:104 arg1 Population 106:115 a Homogeneous Population 92:115 a Homogeneous Population of iPSC-Derived Hepatocytes 92:143 Mapping the Cell-Surface N-Glycoproteome of Human Hepatocytes Reveals Markers for Selecting a Homogeneous Population of iPSC-Derived Hepatocytes. 27569060 4 10 theme expression 536:545 arg1 profiles 547:554 the expression profiles 532:554 the expression profiles during the differentiation of iPSCs 532:590 Analyses of the expression profiles during the differentiation of iPSCs revealed that SLC10A1, CLRN3, and AADAC were highly enriched during the final stages of hepatocyte differentiation. 27569060 5 11 theme cells 745:749 arg1 purification 713:724 FACS purification 708:724 FACS purification of hepatocyte-like cells expressing SLC10A1, CLRN3, or AADAC 708:785 FACS purification of hepatocyte-like cells expressing SLC10A1, CLRN3, or AADAC demonstrated enrichment of cells with hepatocyte characteristics. 27569060 2 12 theme cell 339:342 arg1 populations 344:354 homogeneous cell populations 327:354 homogeneous cell populations 327:354 We proposed that homogeneous cell populations could be generated by fluorescence-activated cell sorting (FACS). 27569060 0 13 theme iPSC-Derived 120:131 arg1 Hepatocytes 133:143 iPSC-Derived Hepatocytes 120:143 iPSC-Derived Hepatocytes 120:143 Mapping the Cell-Surface N-Glycoproteome of Human Hepatocytes Reveals Markers for Selecting a Homogeneous Population of iPSC-Derived Hepatocytes. 27569060 6 14 theme pluripotent 990:1000 arg1 cell 1007:1010 a pluripotent stem cell 988:1010 a pluripotent stem cell network 988:1018 Moreover, transcriptome analyses revealed that cells expressing the liver gene regulatory network were enriched while cells expressing a pluripotent stem cell network were depleted. 27569060 7 15 theme homogeneous 1224:1234 arg1 populations 1236:1246 homogeneous populations 1224:1246 homogeneous populations of iPSC-derived hepatocyte-like cells 1224:1284 In conclusion, we report an extensive catalog of cell-surface N-linked glycoproteins expressed in primary hepatocytes and identify cell-surface proteins that facilitate the purification of homogeneous populations of iPSC-derived hepatocyte-like cells. 27569060 4 16 theme hepatocyte 680:689 arg1 differentiation 691:705 hepatocyte differentiation 680:705 hepatocyte differentiation 680:705 Analyses of the expression profiles during the differentiation of iPSCs revealed that SLC10A1, CLRN3, and AADAC were highly enriched during the final stages of hepatocyte differentiation. 27569060 2 17 theme homogeneous 327:337 arg1 populations 344:354 homogeneous cell populations 327:354 homogeneous cell populations 327:354 We proposed that homogeneous cell populations could be generated by fluorescence-activated cell sorting (FACS). 27569060 1 18 theme hepatocyte-like 201:215 arg1 cells 217:221 iPSC-derived hepatocyte-like cells 188:221 iPSC-derived hepatocyte-like cells from different liver disease patients 188:259 When comparing hepatic phenotypes between iPSC-derived hepatocyte-like cells from different liver disease patients, cell heterogeneity can confound interpretation. 27569060 7 19 theme populations 1236:1246 arg1 purification 1208:1219 the purification 1204:1219 the purification of homogeneous populations of iPSC-derived hepatocyte-like cells 1204:1284 In conclusion, we report an extensive catalog of cell-surface N-linked glycoproteins expressed in primary hepatocytes and identify cell-surface proteins that facilitate the purification of homogeneous populations of iPSC-derived hepatocyte-like cells. 27569060 7 20 theme N-linked 1097:1104 arg1 glycoproteins 1106:1118 cell-surface N-linked glycoproteins 1084:1118 cell-surface N-linked glycoproteins expressed in primary hepatocytes 1084:1151 In conclusion, we report an extensive catalog of cell-surface N-linked glycoproteins expressed in primary hepatocytes and identify cell-surface proteins that facilitate the purification of homogeneous populations of iPSC-derived hepatocyte-like cells. 27569060 5 21 theme cells 814:818 arg1 enrichment 800:809 enrichment 800:809 enrichment of cells with hepatocyte characteristics 800:850 FACS purification of hepatocyte-like cells expressing SLC10A1, CLRN3, or AADAC demonstrated enrichment of cells with hepatocyte characteristics. 27569060 4 22 theme profiles 547:554 arg1 Analyses 520:527 Analyses 520:527 Analyses of the expression profiles during the differentiation of iPSCs 520:590 Analyses of the expression profiles during the differentiation of iPSCs revealed that SLC10A1, CLRN3, and AADAC were highly enriched during the final stages of hepatocyte differentiation. 27569060 5 23 theme FACS 708:711 arg1 purification 713:724 FACS purification 708:724 FACS purification of hepatocyte-like cells expressing SLC10A1, CLRN3, or AADAC 708:785 FACS purification of hepatocyte-like cells expressing SLC10A1, CLRN3, or AADAC demonstrated enrichment of cells with hepatocyte characteristics. 27569060 6 24 theme transcriptome 863:875 arg1 analyses 877:884 transcriptome analyses 863:884 transcriptome analyses 863:884 Moreover, transcriptome analyses revealed that cells expressing the liver gene regulatory network were enriched while cells expressing a pluripotent stem cell network were depleted. 27569060 1 25 theme different 228:236 arg1 patients 252:259 different liver disease patients 228:259 different liver disease patients 228:259 When comparing hepatic phenotypes between iPSC-derived hepatocyte-like cells from different liver disease patients, cell heterogeneity can confound interpretation. 27569060 3 26 theme cell-surface 428:439 arg1 proteomics 449:458 cell-surface capture proteomics 428:458 cell-surface capture proteomics 428:458 Using cell-surface capture proteomics, we identified a total of 300 glycoproteins on hepatocytes. 27569060 1 27 theme liver 238:242 arg1 patients 252:259 different liver disease patients 228:259 different liver disease patients 228:259 When comparing hepatic phenotypes between iPSC-derived hepatocyte-like cells from different liver disease patients, cell heterogeneity can confound interpretation. 27569060 3 28 theme capture 441:447 arg1 proteomics 449:458 cell-surface capture proteomics 428:458 cell-surface capture proteomics 428:458 Using cell-surface capture proteomics, we identified a total of 300 glycoproteins on hepatocytes. 27569060 0 29 theme Hepatocytes 133:143 arg1 Population 106:115 a Homogeneous Population 92:115 a Homogeneous Population of iPSC-Derived Hepatocytes 92:143 Mapping the Cell-Surface N-Glycoproteome of Human Hepatocytes Reveals Markers for Selecting a Homogeneous Population of iPSC-Derived Hepatocytes. 27569060 1 30 theme disease 244:250 arg1 patients 252:259 different liver disease patients 228:259 different liver disease patients 228:259 When comparing hepatic phenotypes between iPSC-derived hepatocyte-like cells from different liver disease patients, cell heterogeneity can confound interpretation. 27569060 0 31 theme Human 44:48 arg1 Hepatocytes 50:60 Human Hepatocytes 44:60 Human Hepatocytes 44:60 Mapping the Cell-Surface N-Glycoproteome of Human Hepatocytes Reveals Markers for Selecting a Homogeneous Population of iPSC-Derived Hepatocytes. 27569060 7 32 link N-linked 1097:1104 arg1 glycoproteins 1106:1118 cell-surface N-linked glycoproteins 1084:1118 cell-surface N-linked glycoproteins expressed in primary hepatocytes 1084:1151 In conclusion, we report an extensive catalog of cell-surface N-linked glycoproteins expressed in primary hepatocytes and identify cell-surface proteins that facilitate the purification of homogeneous populations of iPSC-derived hepatocyte-like cells. 27569060 7 33 link iPSC-derived 1251:1262 arg1 cells 1280:1284 iPSC-derived hepatocyte-like cells 1251:1284 iPSC-derived hepatocyte-like cells 1251:1284 In conclusion, we report an extensive catalog of cell-surface N-linked glycoproteins expressed in primary hepatocytes and identify cell-surface proteins that facilitate the purification of homogeneous populations of iPSC-derived hepatocyte-like cells. 27569060 3 34 theme glycoproteins 490:502 arg1 total 477:481 a total 475:481 a total of 300 glycoproteins 475:502 Using cell-surface capture proteomics, we identified a total of 300 glycoproteins on hepatocytes. 27569060 1 35 from patients 252:259 arg1 cells 217:221 iPSC-derived hepatocyte-like cells 188:221 iPSC-derived hepatocyte-like cells from different liver disease patients 188:259 When comparing hepatic phenotypes between iPSC-derived hepatocyte-like cells from different liver disease patients, cell heterogeneity can confound interpretation. 27569060 5 36 with enrichment 800:809 arg1 characteristics 836:850 hepatocyte characteristics 825:850 hepatocyte characteristics 825:850 FACS purification of hepatocyte-like cells expressing SLC10A1, CLRN3, or AADAC demonstrated enrichment of cells with hepatocyte characteristics. 27569060 7 37 theme primary 1133:1139 arg1 hepatocytes 1141:1151 primary hepatocytes 1133:1151 primary hepatocytes 1133:1151 In conclusion, we report an extensive catalog of cell-surface N-linked glycoproteins expressed in primary hepatocytes and identify cell-surface proteins that facilitate the purification of homogeneous populations of iPSC-derived hepatocyte-like cells. 27569060 0 38 theme Hepatocytes 50:60 arg1 N-Glycoproteome 25:39 the Cell-Surface N-Glycoproteome 8:39 the Cell-Surface N-Glycoproteome of Human Hepatocytes 8:60 Mapping the Cell-Surface N-Glycoproteome of Human Hepatocytes Reveals Markers for Selecting a Homogeneous Population of iPSC-Derived Hepatocytes. 27569060 7 39 theme cell-surface 1166:1177 arg1 proteins 1179:1186 cell-surface proteins 1166:1186 cell-surface proteins that facilitate the purification of homogeneous populations of iPSC-derived hepatocyte-like cells 1166:1284 In conclusion, we report an extensive catalog of cell-surface N-linked glycoproteins expressed in primary hepatocytes and identify cell-surface proteins that facilitate the purification of homogeneous populations of iPSC-derived hepatocyte-like cells. 27569060 7 40 theme glycoproteins 1106:1118 arg1 catalog 1073:1079 an extensive catalog 1060:1079 an extensive catalog of cell-surface N-linked glycoproteins expressed in primary hepatocytes 1060:1151 In conclusion, we report an extensive catalog of cell-surface N-linked glycoproteins expressed in primary hepatocytes and identify cell-surface proteins that facilitate the purification of homogeneous populations of iPSC-derived hepatocyte-like cells. 27569060 7 41 gly glycoproteins 1106:1118 arg1 glycoproteins 1106:1118 cell-surface N-linked glycoproteins 1084:1118 cell-surface N-linked glycoproteins expressed in primary hepatocytes 1084:1151 In conclusion, we report an extensive catalog of cell-surface N-linked glycoproteins expressed in primary hepatocytes and identify cell-surface proteins that facilitate the purification of homogeneous populations of iPSC-derived hepatocyte-like cells. 27569060 6 42 theme regulatory 932:941 arg1 network 943:949 the liver gene regulatory network 917:949 the liver gene regulatory network 917:949 Moreover, transcriptome analyses revealed that cells expressing the liver gene regulatory network were enriched while cells expressing a pluripotent stem cell network were depleted. 27569060 2 43 theme cell 401:404 arg1 sorting 406:412 fluorescence-activated cell sorting 378:412 fluorescence-activated cell sorting (FACS) 378:419 We proposed that homogeneous cell populations could be generated by fluorescence-activated cell sorting (FACS). 27569060 2 43 theme cell 401:404 arg1 FACS 415:418 FACS 415:418 FACS 415:418 We proposed that homogeneous cell populations could be generated by fluorescence-activated cell sorting (FACS). 27569060 1 44 theme cell 262:265 arg1 heterogeneity 267:279 cell heterogeneity 262:279 cell heterogeneity 262:279 When comparing hepatic phenotypes between iPSC-derived hepatocyte-like cells from different liver disease patients, cell heterogeneity can confound interpretation. 27569060 6 45 theme gene 927:930 arg1 network 943:949 the liver gene regulatory network 917:949 the liver gene regulatory network 917:949 Moreover, transcriptome analyses revealed that cells expressing the liver gene regulatory network were enriched while cells expressing a pluripotent stem cell network were depleted. 27569060 3 46 gly glycoproteins 490:502 arg1 glycoproteins 490:502 300 glycoproteins 486:502 300 glycoproteins 486:502 Using cell-surface capture proteomics, we identified a total of 300 glycoproteins on hepatocytes. 27569060 7 47 theme cell-surface 1084:1095 arg1 glycoproteins 1106:1118 cell-surface N-linked glycoproteins 1084:1118 cell-surface N-linked glycoproteins expressed in primary hepatocytes 1084:1151 In conclusion, we report an extensive catalog of cell-surface N-linked glycoproteins expressed in primary hepatocytes and identify cell-surface proteins that facilitate the purification of homogeneous populations of iPSC-derived hepatocyte-like cells. 27569060 2 48 theme fluorescence-activated 378:399 arg1 sorting 406:412 fluorescence-activated cell sorting 378:412 fluorescence-activated cell sorting (FACS) 378:419 We proposed that homogeneous cell populations could be generated by fluorescence-activated cell sorting (FACS). 27569060 2 48 theme fluorescence-activated 378:399 arg1 FACS 415:418 FACS 415:418 FACS 415:418 We proposed that homogeneous cell populations could be generated by fluorescence-activated cell sorting (FACS). 27569060 5 49 theme hepatocyte 825:834 arg1 characteristics 836:850 hepatocyte characteristics 825:850 hepatocyte characteristics 825:850 FACS purification of hepatocyte-like cells expressing SLC10A1, CLRN3, or AADAC demonstrated enrichment of cells with hepatocyte characteristics. 27569060 6 50 theme liver 921:925 arg1 network 943:949 the liver gene regulatory network 917:949 the liver gene regulatory network 917:949 Moreover, transcriptome analyses revealed that cells expressing the liver gene regulatory network were enriched while cells expressing a pluripotent stem cell network were depleted. 27569060 4 51 theme differentiation 691:705 arg1 stages 670:675 the final stages 660:675 the final stages of hepatocyte differentiation 660:705 Analyses of the expression profiles during the differentiation of iPSCs revealed that SLC10A1, CLRN3, and AADAC were highly enriched during the final stages of hepatocyte differentiation. 27569060 1 52 theme hepatic 161:167 arg1 phenotypes 169:178 hepatic phenotypes 161:178 hepatic phenotypes 161:178 When comparing hepatic phenotypes between iPSC-derived hepatocyte-like cells from different liver disease patients, cell heterogeneity can confound interpretation. 27569060 0 53 theme Cell-Surface 12:23 arg1 N-Glycoproteome 25:39 the Cell-Surface N-Glycoproteome 8:39 the Cell-Surface N-Glycoproteome of Human Hepatocytes 8:60 Mapping the Cell-Surface N-Glycoproteome of Human Hepatocytes Reveals Markers for Selecting a Homogeneous Population of iPSC-Derived Hepatocytes. 27569060 4 54 theme final 664:668 arg1 stages 670:675 the final stages 660:675 the final stages of hepatocyte differentiation 660:705 Analyses of the expression profiles during the differentiation of iPSCs revealed that SLC10A1, CLRN3, and AADAC were highly enriched during the final stages of hepatocyte differentiation. 27569060 7 55 theme iPSC-derived 1251:1262 arg1 cells 1280:1284 iPSC-derived hepatocyte-like cells 1251:1284 iPSC-derived hepatocyte-like cells 1251:1284 In conclusion, we report an extensive catalog of cell-surface N-linked glycoproteins expressed in primary hepatocytes and identify cell-surface proteins that facilitate the purification of homogeneous populations of iPSC-derived hepatocyte-like cells. 26877109 0 0 from analysis 33:40 arg1 LPL 45:47 LPL 45:47 LPL of Coilia nasus 45:63 Molecular cloning and expression analysis on LPL of Coilia nasus. 26877109 5 1 theme bp 580:581 arg1 frame 596:600 a 1519 bp open reading frame 573:600 a 1519 bp open reading frame encoding 505 deduced amino acids whose molecular mass was 57.5 kDa and theoretical isoelectric point was 7.58 573:710 A full-length cDNA of LPL of C. nasus was cloned from liver which covered 3537 bp with a 1519 bp open reading frame encoding 505 deduced amino acids whose molecular mass was 57.5 kDa and theoretical isoelectric point was 7.58. 26877109 11 2 theme head 1383:1386 arg1 kidney 1388:1393 head kidney 1383:1393 head kidney 1383:1393 Lipid expressed lowly in spleen, heart, head kidney, trunk kidney, gill and brain. 26877109 8 3 theme mesenteric 1073:1082 arg1 adipose 1084:1090 mesenteric adipose 1073:1090 mesenteric adipose 1073:1090 We adopted quantitative real-time RT-PCR method to detect the mRNA expression of LPL of C. nasus in ten tissues including mesenteric adipose, liver, muscle, stomach, spleen, heart, head kidney, trunk kidney, gill and brain with β-actin as internal reference. 26877109 12 4 theme nasus 1568:1572 arg1 metabolism 1551:1560 lipid metabolism 1545:1560 lipid metabolism of C. nasus 1545:1572 The research on the cloning and differential expression of LPL of C. nasus will lay foundation for further research on lipid metabolism of C. nasus. 26877109 5 5 theme reading 588:594 arg1 frame 596:600 a 1519 bp open reading frame 573:600 a 1519 bp open reading frame encoding 505 deduced amino acids whose molecular mass was 57.5 kDa and theoretical isoelectric point was 7.58 573:710 A full-length cDNA of LPL of C. nasus was cloned from liver which covered 3537 bp with a 1519 bp open reading frame encoding 505 deduced amino acids whose molecular mass was 57.5 kDa and theoretical isoelectric point was 7.58. 26877109 6 6 theme amino 725:729 arg1 acids 731:735 The deduced amino acids 713:735 The deduced amino acids 713:735 The deduced amino acids had high similarity with the reported LPL sequence of other species. 26877109 2 7 theme Protective 227:236 arg1 List 246:249 the "National Key Protective Species List 209:249 the "National Key Protective Species List" because of its severe resource damage 209:288 At present, it has been on the "National Key Protective Species List" because of its severe resource damage. 26877109 6 8 theme other 791:795 arg1 species 797:803 other species 791:803 other species 791:803 The deduced amino acids had high similarity with the reported LPL sequence of other species. 26877109 12 9 theme lipid 1545:1549 arg1 metabolism 1551:1560 lipid metabolism 1545:1560 lipid metabolism of C. nasus 1545:1572 The research on the cloning and differential expression of LPL of C. nasus will lay foundation for further research on lipid metabolism of C. nasus. 26877109 8 10 theme trunk 1145:1149 arg1 adipose 1084:1090 mesenteric adipose 1073:1090 mesenteric adipose 1073:1090 We adopted quantitative real-time RT-PCR method to detect the mRNA expression of LPL of C. nasus in ten tissues including mesenteric adipose, liver, muscle, stomach, spleen, heart, head kidney, trunk kidney, gill and brain with β-actin as internal reference. 26877109 8 10 theme trunk 1145:1149 arg1 tissues 1055:1061 ten tissues 1051:1061 ten tissues including mesenteric adipose 1051:1090 We adopted quantitative real-time RT-PCR method to detect the mRNA expression of LPL of C. nasus in ten tissues including mesenteric adipose, liver, muscle, stomach, spleen, heart, head kidney, trunk kidney, gill and brain with β-actin as internal reference. 26877109 8 10 theme trunk 1145:1149 arg1 kidney 1151:1156 trunk kidney 1145:1156 trunk kidney 1145:1156 We adopted quantitative real-time RT-PCR method to detect the mRNA expression of LPL of C. nasus in ten tissues including mesenteric adipose, liver, muscle, stomach, spleen, heart, head kidney, trunk kidney, gill and brain with β-actin as internal reference. 26877109 5 11 theme LPL 508:510 arg1 cDNA 500:503 A full-length cDNA 486:503 A full-length cDNA of LPL of C. nasus 486:522 A full-length cDNA of LPL of C. nasus was cloned from liver which covered 3537 bp with a 1519 bp open reading frame encoding 505 deduced amino acids whose molecular mass was 57.5 kDa and theoretical isoelectric point was 7.58. 26877109 5 12 theme molecular 641:649 arg1 mass 651:654 mass 651:654 mass 651:654 A full-length cDNA of LPL of C. nasus was cloned from liver which covered 3537 bp with a 1519 bp open reading frame encoding 505 deduced amino acids whose molecular mass was 57.5 kDa and theoretical isoelectric point was 7.58. 26877109 4 13 theme nasus 413:417 arg1 metabolism 396:405 lipid metabolism 390:405 lipid metabolism of C. nasus 390:417 To make further research on lipid metabolism of C. nasus, we cloned lipoprotein lipase gene with homologous cloning method. 26877109 7 14 theme heparin-binding 924:938 arg1 site 940:943 conserved heparin-binding site 914:943 conserved heparin-binding site 914:943 It had typical conserved domain of LPL protein containing catalytic triad, N-linked glycosylation sites and conserved heparin-binding site, etc. 26877109 7 14 theme heparin-binding 924:938 arg1 etc 946:948 etc 946:948 etc 946:948 It had typical conserved domain of LPL protein containing catalytic triad, N-linked glycosylation sites and conserved heparin-binding site, etc. 26877109 1 15 theme anadromous 107:116 arg1 species 118:124 one important commercial anadromous species 82:124 one important commercial anadromous species which mainly distributed in the Yangtze River in China 82:179 Coilia nasus is one important commercial anadromous species which mainly distributed in the Yangtze River in China. 26877109 12 16 theme further 1525:1531 arg1 research 1533:1540 further research 1525:1540 further research on lipid metabolism of C. nasus 1525:1572 The research on the cloning and differential expression of LPL of C. nasus will lay foundation for further research on lipid metabolism of C. nasus. 26877109 5 17 theme deduced 615:621 arg1 acids 629:633 505 deduced amino acids 611:633 505 deduced amino acids whose molecular mass was 57.5 kDa and theoretical isoelectric point was 7.58 611:710 A full-length cDNA of LPL of C. nasus was cloned from liver which covered 3537 bp with a 1519 bp open reading frame encoding 505 deduced amino acids whose molecular mass was 57.5 kDa and theoretical isoelectric point was 7.58. 26877109 2 18 theme National 214:221 arg1 List 246:249 the "National Key Protective Species List 209:249 the "National Key Protective Species List" because of its severe resource damage 209:288 At present, it has been on the "National Key Protective Species List" because of its severe resource damage. 26877109 4 19 theme lipid 390:394 arg1 metabolism 396:405 lipid metabolism 390:405 lipid metabolism of C. nasus 390:417 To make further research on lipid metabolism of C. nasus, we cloned lipoprotein lipase gene with homologous cloning method. 26877109 0 20 theme Coilia 52:57 arg1 nasus 59:63 Coilia nasus 52:63 Coilia nasus 52:63 Molecular cloning and expression analysis on LPL of Coilia nasus. 26877109 7 21 theme glycosylation 890:902 arg1 sites 904:908 catalytic triad, N-linked glycosylation sites 864:908 sites 904:908 It had typical conserved domain of LPL protein containing catalytic triad, N-linked glycosylation sites and conserved heparin-binding site, etc. 26877109 4 22 from research 378:385 arg1 metabolism 396:405 lipid metabolism 390:405 lipid metabolism of C. nasus 390:417 To make further research on lipid metabolism of C. nasus, we cloned lipoprotein lipase gene with homologous cloning method. 26877109 4 23 theme homologous 459:468 arg1 method 478:483 homologous cloning method 459:483 homologous cloning method 459:483 To make further research on lipid metabolism of C. nasus, we cloned lipoprotein lipase gene with homologous cloning method. 26877109 7 24 theme catalytic 864:872 arg1 sites 904:908 catalytic triad, N-linked glycosylation sites 864:908 sites 904:908 It had typical conserved domain of LPL protein containing catalytic triad, N-linked glycosylation sites and conserved heparin-binding site, etc. 26877109 12 25 theme LPL 1485:1487 arg1 cloning 1446:1452 cloning 1446:1452 cloning 1446:1452 The research on the cloning and differential expression of LPL of C. nasus will lay foundation for further research on lipid metabolism of C. nasus. 26877109 12 25 theme LPL 1485:1487 arg1 expression 1471:1480 differential expression 1458:1480 differential expression 1458:1480 The research on the cloning and differential expression of LPL of C. nasus will lay foundation for further research on lipid metabolism of C. nasus. 26877109 8 26 theme real-time 975:983 arg1 method 992:997 quantitative real-time RT-PCR method 962:997 quantitative real-time RT-PCR method 962:997 We adopted quantitative real-time RT-PCR method to detect the mRNA expression of LPL of C. nasus in ten tissues including mesenteric adipose, liver, muscle, stomach, spleen, heart, head kidney, trunk kidney, gill and brain with β-actin as internal reference. 26877109 7 27 theme protein 845:851 arg1 protein 845:851 LPL protein 841:851 LPL protein 841:851 It had typical conserved domain of LPL protein containing catalytic triad, N-linked glycosylation sites and conserved heparin-binding site, etc. 26877109 7 27 theme protein 845:851 arg1 domain 831:836 typical conserved domain 813:836 typical conserved domain of LPL protein containing catalytic triad, N-linked glycosylation sites and conserved heparin-binding site, etc 813:948 It had typical conserved domain of LPL protein containing catalytic triad, N-linked glycosylation sites and conserved heparin-binding site, etc. 26877109 1 28 theme Coilia 66:71 arg1 nasus 73:77 Coilia nasus 66:77 Coilia nasus 66:77 Coilia nasus is one important commercial anadromous species which mainly distributed in the Yangtze River in China. 26877109 3 29 theme long-distance 337:349 arg1 migration 351:359 its long-distance migration 333:359 its long-distance migration 333:359 Lipid metabolism is very important during its long-distance migration. 26877109 4 30 theme lipoprotein 430:440 arg1 lipase 442:447 lipoprotein lipase 430:447 lipoprotein lipase gene 430:452 To make further research on lipid metabolism of C. nasus, we cloned lipoprotein lipase gene with homologous cloning method. 26877109 0 31 theme Molecular 0:8 arg1 cloning 10:16 Molecular cloning 0:16 Molecular cloning 0:16 Molecular cloning and expression analysis on LPL of Coilia nasus. 26877109 8 32 from tissues 1055:1061 arg1 expression 1018:1027 the mRNA expression 1009:1027 the mRNA expression of LPL of C. nasus in ten tissues including mesenteric adipose, liver, muscle, stomach, spleen, heart, head kidney, trunk kidney, gill and brain 1009:1172 We adopted quantitative real-time RT-PCR method to detect the mRNA expression of LPL of C. nasus in ten tissues including mesenteric adipose, liver, muscle, stomach, spleen, heart, head kidney, trunk kidney, gill and brain with β-actin as internal reference. 26877109 1 33 theme important 86:94 arg1 species 118:124 one important commercial anadromous species 82:124 one important commercial anadromous species which mainly distributed in the Yangtze River in China 82:179 Coilia nasus is one important commercial anadromous species which mainly distributed in the Yangtze River in China. 26877109 7 34 gly glycosylation 890:902 arg2 sites 904:908 catalytic triad, N-linked glycosylation sites 864:908 sites 904:908 It had typical conserved domain of LPL protein containing catalytic triad, N-linked glycosylation sites and conserved heparin-binding site, etc. 26877109 8 35 theme mRNA 1013:1016 arg1 expression 1018:1027 the mRNA expression 1009:1027 the mRNA expression of LPL of C. nasus in ten tissues including mesenteric adipose, liver, muscle, stomach, spleen, heart, head kidney, trunk kidney, gill and brain 1009:1172 We adopted quantitative real-time RT-PCR method to detect the mRNA expression of LPL of C. nasus in ten tissues including mesenteric adipose, liver, muscle, stomach, spleen, heart, head kidney, trunk kidney, gill and brain with β-actin as internal reference. 26877109 6 36 theme LPL 775:777 arg1 sequence 779:786 the reported LPL sequence 762:786 the reported LPL sequence of other species 762:803 The deduced amino acids had high similarity with the reported LPL sequence of other species. 26877109 5 37 theme theoretical 673:683 arg1 point 697:701 theoretical isoelectric point 673:701 theoretical isoelectric point 673:701 A full-length cDNA of LPL of C. nasus was cloned from liver which covered 3537 bp with a 1519 bp open reading frame encoding 505 deduced amino acids whose molecular mass was 57.5 kDa and theoretical isoelectric point was 7.58. 26877109 9 38 theme detected 1235:1242 arg1 tissues 1244:1250 all the detected tissues 1227:1250 all the detected tissues 1227:1250 LPL expressed in all the detected tissues. 26877109 7 39 theme typical 813:819 arg1 protein 845:851 LPL protein 841:851 LPL protein 841:851 It had typical conserved domain of LPL protein containing catalytic triad, N-linked glycosylation sites and conserved heparin-binding site, etc. 26877109 7 39 theme typical 813:819 arg1 domain 831:836 typical conserved domain 813:836 typical conserved domain of LPL protein containing catalytic triad, N-linked glycosylation sites and conserved heparin-binding site, etc 813:948 It had typical conserved domain of LPL protein containing catalytic triad, N-linked glycosylation sites and conserved heparin-binding site, etc. 26877109 8 40 theme nasus 1042:1046 arg1 LPL 1032:1034 LPL 1032:1034 LPL of C. nasus in ten tissues including mesenteric adipose, liver, muscle, stomach, spleen, heart, head kidney, trunk kidney, gill and brain 1032:1172 We adopted quantitative real-time RT-PCR method to detect the mRNA expression of LPL of C. nasus in ten tissues including mesenteric adipose, liver, muscle, stomach, spleen, heart, head kidney, trunk kidney, gill and brain with β-actin as internal reference. 26877109 5 41 theme 1519 575:578 arg1 bp 580:581 bp 580:581 bp 580:581 A full-length cDNA of LPL of C. nasus was cloned from liver which covered 3537 bp with a 1519 bp open reading frame encoding 505 deduced amino acids whose molecular mass was 57.5 kDa and theoretical isoelectric point was 7.58. 26877109 5 42 theme open 583:586 arg1 frame 596:600 a 1519 bp open reading frame 573:600 a 1519 bp open reading frame encoding 505 deduced amino acids whose molecular mass was 57.5 kDa and theoretical isoelectric point was 7.58 573:710 A full-length cDNA of LPL of C. nasus was cloned from liver which covered 3537 bp with a 1519 bp open reading frame encoding 505 deduced amino acids whose molecular mass was 57.5 kDa and theoretical isoelectric point was 7.58. 26877109 10 43 theme highest 1257:1263 arg1 expression 1265:1274 The highest expression 1253:1274 The highest expression 1253:1274 The highest expression was in mesenteric adipose, and followed by liver, muscle, stomach. 26877109 4 44 theme further 370:376 arg1 research 378:385 further research 370:385 further research on lipid metabolism of C. nasus 370:417 To make further research on lipid metabolism of C. nasus, we cloned lipoprotein lipase gene with homologous cloning method. 26877109 6 45 theme deduced 717:723 arg1 acids 731:735 The deduced amino acids 713:735 The deduced amino acids 713:735 The deduced amino acids had high similarity with the reported LPL sequence of other species. 26877109 2 46 theme Species 238:244 arg1 List 246:249 the "National Key Protective Species List 209:249 the "National Key Protective Species List" because of its severe resource damage 209:288 At present, it has been on the "National Key Protective Species List" because of its severe resource damage. 26877109 2 47 from present 185:191 arg1 List 246:249 the "National Key Protective Species List 209:249 the "National Key Protective Species List" because of its severe resource damage 209:288 At present, it has been on the "National Key Protective Species List" because of its severe resource damage. 26877109 6 48 theme species 797:803 arg1 sequence 779:786 the reported LPL sequence 762:786 the reported LPL sequence of other species 762:803 The deduced amino acids had high similarity with the reported LPL sequence of other species. 26877109 10 49 theme mesenteric 1283:1292 arg1 adipose 1294:1300 mesenteric adipose 1283:1300 mesenteric adipose 1283:1300 The highest expression was in mesenteric adipose, and followed by liver, muscle, stomach. 26877109 2 50 theme severe 267:272 arg1 damage 283:288 its severe resource damage 263:288 its severe resource damage 263:288 At present, it has been on the "National Key Protective Species List" because of its severe resource damage. 26877109 4 51 theme cloning 470:476 arg1 method 478:483 homologous cloning method 459:483 homologous cloning method 459:483 To make further research on lipid metabolism of C. nasus, we cloned lipoprotein lipase gene with homologous cloning method. 26877109 5 52 dep 7.58 707:710 arg1 kDa 665:667 57.5 kDa 660:667 57.5 kDa 660:667 A full-length cDNA of LPL of C. nasus was cloned from liver which covered 3537 bp with a 1519 bp open reading frame encoding 505 deduced amino acids whose molecular mass was 57.5 kDa and theoretical isoelectric point was 7.58. 26877109 5 52 dep 7.58 707:710 arg1 point 697:701 theoretical isoelectric point 673:701 theoretical isoelectric point 673:701 A full-length cDNA of LPL of C. nasus was cloned from liver which covered 3537 bp with a 1519 bp open reading frame encoding 505 deduced amino acids whose molecular mass was 57.5 kDa and theoretical isoelectric point was 7.58. 26877109 8 53 theme head 1132:1135 arg1 tissues 1055:1061 ten tissues 1051:1061 ten tissues including mesenteric adipose 1051:1090 We adopted quantitative real-time RT-PCR method to detect the mRNA expression of LPL of C. nasus in ten tissues including mesenteric adipose, liver, muscle, stomach, spleen, heart, head kidney, trunk kidney, gill and brain with β-actin as internal reference. 26877109 8 53 theme head 1132:1135 arg1 kidney 1137:1142 head kidney 1132:1142 head kidney 1132:1142 We adopted quantitative real-time RT-PCR method to detect the mRNA expression of LPL of C. nasus in ten tissues including mesenteric adipose, liver, muscle, stomach, spleen, heart, head kidney, trunk kidney, gill and brain with β-actin as internal reference. 26877109 8 53 theme head 1132:1135 arg1 adipose 1084:1090 mesenteric adipose 1073:1090 mesenteric adipose 1073:1090 We adopted quantitative real-time RT-PCR method to detect the mRNA expression of LPL of C. nasus in ten tissues including mesenteric adipose, liver, muscle, stomach, spleen, heart, head kidney, trunk kidney, gill and brain with β-actin as internal reference. 26877109 7 54 contain containing 853:862 arg2 etc 946:948 etc 946:948 etc 946:948 It had typical conserved domain of LPL protein containing catalytic triad, N-linked glycosylation sites and conserved heparin-binding site, etc. 26877109 7 54 contain containing 853:862 arg1 protein 845:851 LPL protein 841:851 LPL protein 841:851 It had typical conserved domain of LPL protein containing catalytic triad, N-linked glycosylation sites and conserved heparin-binding site, etc. 26877109 7 54 contain containing 853:862 arg2 site 940:943 conserved heparin-binding site 914:943 conserved heparin-binding site 914:943 It had typical conserved domain of LPL protein containing catalytic triad, N-linked glycosylation sites and conserved heparin-binding site, etc. 26877109 7 54 contain containing 853:862 arg2 sites 904:908 catalytic triad, N-linked glycosylation sites 864:908 sites 904:908 It had typical conserved domain of LPL protein containing catalytic triad, N-linked glycosylation sites and conserved heparin-binding site, etc. 26877109 7 54 contain containing 853:862 arg1 domain 831:836 typical conserved domain 813:836 typical conserved domain of LPL protein containing catalytic triad, N-linked glycosylation sites and conserved heparin-binding site, etc 813:948 It had typical conserved domain of LPL protein containing catalytic triad, N-linked glycosylation sites and conserved heparin-binding site, etc. 26877109 5 55 theme amino 623:627 arg1 acids 629:633 505 deduced amino acids 611:633 505 deduced amino acids whose molecular mass was 57.5 kDa and theoretical isoelectric point was 7.58 611:710 A full-length cDNA of LPL of C. nasus was cloned from liver which covered 3537 bp with a 1519 bp open reading frame encoding 505 deduced amino acids whose molecular mass was 57.5 kDa and theoretical isoelectric point was 7.58. 26877109 11 56 theme trunk 1396:1400 arg1 kidney 1402:1407 trunk kidney 1396:1407 trunk kidney 1396:1407 Lipid expressed lowly in spleen, heart, head kidney, trunk kidney, gill and brain. 26877109 12 57 from research 1533:1540 arg1 metabolism 1551:1560 lipid metabolism 1545:1560 lipid metabolism of C. nasus 1545:1572 The research on the cloning and differential expression of LPL of C. nasus will lay foundation for further research on lipid metabolism of C. nasus. 26877109 1 58 theme commercial 96:105 arg1 species 118:124 one important commercial anadromous species 82:124 one important commercial anadromous species which mainly distributed in the Yangtze River in China 82:179 Coilia nasus is one important commercial anadromous species which mainly distributed in the Yangtze River in China. 26877109 2 59 theme Key 223:225 arg1 List 246:249 the "National Key Protective Species List 209:249 the "National Key Protective Species List" because of its severe resource damage 209:288 At present, it has been on the "National Key Protective Species List" because of its severe resource damage. 26877109 8 60 from expression 1018:1027 arg1 muscle 1100:1105 muscle 1100:1105 muscle 1100:1105 We adopted quantitative real-time RT-PCR method to detect the mRNA expression of LPL of C. nasus in ten tissues including mesenteric adipose, liver, muscle, stomach, spleen, heart, head kidney, trunk kidney, gill and brain with β-actin as internal reference. 26877109 8 60 from expression 1018:1027 arg1 heart 1125:1129 heart 1125:1129 heart 1125:1129 We adopted quantitative real-time RT-PCR method to detect the mRNA expression of LPL of C. nasus in ten tissues including mesenteric adipose, liver, muscle, stomach, spleen, heart, head kidney, trunk kidney, gill and brain with β-actin as internal reference. 26877109 8 60 from expression 1018:1027 arg1 gill 1159:1162 gill 1159:1162 gill 1159:1162 We adopted quantitative real-time RT-PCR method to detect the mRNA expression of LPL of C. nasus in ten tissues including mesenteric adipose, liver, muscle, stomach, spleen, heart, head kidney, trunk kidney, gill and brain with β-actin as internal reference. 26877109 8 60 from expression 1018:1027 arg1 kidney 1137:1142 head kidney 1132:1142 head kidney 1132:1142 We adopted quantitative real-time RT-PCR method to detect the mRNA expression of LPL of C. nasus in ten tissues including mesenteric adipose, liver, muscle, stomach, spleen, heart, head kidney, trunk kidney, gill and brain with β-actin as internal reference. 26877109 8 60 from expression 1018:1027 arg1 adipose 1084:1090 mesenteric adipose 1073:1090 mesenteric adipose 1073:1090 We adopted quantitative real-time RT-PCR method to detect the mRNA expression of LPL of C. nasus in ten tissues including mesenteric adipose, liver, muscle, stomach, spleen, heart, head kidney, trunk kidney, gill and brain with β-actin as internal reference. 26877109 8 60 from expression 1018:1027 arg1 stomach 1108:1114 stomach 1108:1114 stomach 1108:1114 We adopted quantitative real-time RT-PCR method to detect the mRNA expression of LPL of C. nasus in ten tissues including mesenteric adipose, liver, muscle, stomach, spleen, heart, head kidney, trunk kidney, gill and brain with β-actin as internal reference. 26877109 8 60 from expression 1018:1027 arg1 brain 1168:1172 brain 1168:1172 brain 1168:1172 We adopted quantitative real-time RT-PCR method to detect the mRNA expression of LPL of C. nasus in ten tissues including mesenteric adipose, liver, muscle, stomach, spleen, heart, head kidney, trunk kidney, gill and brain with β-actin as internal reference. 26877109 8 60 from expression 1018:1027 arg1 spleen 1117:1122 spleen 1117:1122 spleen 1117:1122 We adopted quantitative real-time RT-PCR method to detect the mRNA expression of LPL of C. nasus in ten tissues including mesenteric adipose, liver, muscle, stomach, spleen, heart, head kidney, trunk kidney, gill and brain with β-actin as internal reference. 26877109 8 60 from expression 1018:1027 arg1 liver 1093:1097 liver 1093:1097 liver 1093:1097 We adopted quantitative real-time RT-PCR method to detect the mRNA expression of LPL of C. nasus in ten tissues including mesenteric adipose, liver, muscle, stomach, spleen, heart, head kidney, trunk kidney, gill and brain with β-actin as internal reference. 26877109 8 60 from expression 1018:1027 arg1 tissues 1055:1061 ten tissues 1051:1061 ten tissues including mesenteric adipose 1051:1090 We adopted quantitative real-time RT-PCR method to detect the mRNA expression of LPL of C. nasus in ten tissues including mesenteric adipose, liver, muscle, stomach, spleen, heart, head kidney, trunk kidney, gill and brain with β-actin as internal reference. 26877109 8 60 from expression 1018:1027 arg1 kidney 1151:1156 trunk kidney 1145:1156 trunk kidney 1145:1156 We adopted quantitative real-time RT-PCR method to detect the mRNA expression of LPL of C. nasus in ten tissues including mesenteric adipose, liver, muscle, stomach, spleen, heart, head kidney, trunk kidney, gill and brain with β-actin as internal reference. 26877109 0 61 theme nasus 59:63 arg1 LPL 45:47 LPL 45:47 LPL of Coilia nasus 45:63 Molecular cloning and expression analysis on LPL of Coilia nasus. 26877109 7 62 theme conserved 914:922 arg1 site 940:943 conserved heparin-binding site 914:943 conserved heparin-binding site 914:943 It had typical conserved domain of LPL protein containing catalytic triad, N-linked glycosylation sites and conserved heparin-binding site, etc. 26877109 7 62 theme conserved 914:922 arg1 etc 946:948 etc 946:948 etc 946:948 It had typical conserved domain of LPL protein containing catalytic triad, N-linked glycosylation sites and conserved heparin-binding site, etc. 26877109 3 63 theme Lipid 291:295 arg1 metabolism 297:306 Lipid metabolism 291:306 Lipid metabolism 291:306 Lipid metabolism is very important during its long-distance migration. 26877109 5 64 theme isoelectric 685:695 arg1 point 697:701 theoretical isoelectric point 673:701 theoretical isoelectric point 673:701 A full-length cDNA of LPL of C. nasus was cloned from liver which covered 3537 bp with a 1519 bp open reading frame encoding 505 deduced amino acids whose molecular mass was 57.5 kDa and theoretical isoelectric point was 7.58. 26877109 5 65 theme full-length 488:498 arg1 cDNA 500:503 A full-length cDNA 486:503 A full-length cDNA of LPL of C. nasus 486:522 A full-length cDNA of LPL of C. nasus was cloned from liver which covered 3537 bp with a 1519 bp open reading frame encoding 505 deduced amino acids whose molecular mass was 57.5 kDa and theoretical isoelectric point was 7.58. 26877109 12 66 theme nasus 1495:1499 arg1 cloning 1446:1452 cloning 1446:1452 cloning 1446:1452 The research on the cloning and differential expression of LPL of C. nasus will lay foundation for further research on lipid metabolism of C. nasus. 26877109 12 66 theme nasus 1495:1499 arg1 expression 1471:1480 differential expression 1458:1480 differential expression 1458:1480 The research on the cloning and differential expression of LPL of C. nasus will lay foundation for further research on lipid metabolism of C. nasus. 26877109 6 67 contain had 737:739 arg1 acids 731:735 The deduced amino acids 713:735 The deduced amino acids 713:735 The deduced amino acids had high similarity with the reported LPL sequence of other species. 26877109 6 67 contain had 737:739 arg2 similarity 746:755 high similarity 741:755 high similarity with the reported LPL sequence of other species 741:803 The deduced amino acids had high similarity with the reported LPL sequence of other species. 26877109 0 68 from cloning 10:16 arg1 LPL 45:47 LPL 45:47 LPL of Coilia nasus 45:63 Molecular cloning and expression analysis on LPL of Coilia nasus. 26877109 8 69 theme internal 1190:1197 arg1 reference 1199:1207 internal reference 1190:1207 internal reference 1190:1207 We adopted quantitative real-time RT-PCR method to detect the mRNA expression of LPL of C. nasus in ten tissues including mesenteric adipose, liver, muscle, stomach, spleen, heart, head kidney, trunk kidney, gill and brain with β-actin as internal reference. 26877109 8 70 theme quantitative 962:973 arg1 method 992:997 quantitative real-time RT-PCR method 962:997 quantitative real-time RT-PCR method 962:997 We adopted quantitative real-time RT-PCR method to detect the mRNA expression of LPL of C. nasus in ten tissues including mesenteric adipose, liver, muscle, stomach, spleen, heart, head kidney, trunk kidney, gill and brain with β-actin as internal reference. 26877109 7 71 theme N-linked 881:888 arg1 sites 904:908 catalytic triad, N-linked glycosylation sites 864:908 sites 904:908 It had typical conserved domain of LPL protein containing catalytic triad, N-linked glycosylation sites and conserved heparin-binding site, etc. 26877109 8 72 from LPL 1032:1034 arg1 muscle 1100:1105 muscle 1100:1105 muscle 1100:1105 We adopted quantitative real-time RT-PCR method to detect the mRNA expression of LPL of C. nasus in ten tissues including mesenteric adipose, liver, muscle, stomach, spleen, heart, head kidney, trunk kidney, gill and brain with β-actin as internal reference. 26877109 8 72 from LPL 1032:1034 arg1 heart 1125:1129 heart 1125:1129 heart 1125:1129 We adopted quantitative real-time RT-PCR method to detect the mRNA expression of LPL of C. nasus in ten tissues including mesenteric adipose, liver, muscle, stomach, spleen, heart, head kidney, trunk kidney, gill and brain with β-actin as internal reference. 26877109 8 72 from LPL 1032:1034 arg1 gill 1159:1162 gill 1159:1162 gill 1159:1162 We adopted quantitative real-time RT-PCR method to detect the mRNA expression of LPL of C. nasus in ten tissues including mesenteric adipose, liver, muscle, stomach, spleen, heart, head kidney, trunk kidney, gill and brain with β-actin as internal reference. 26877109 8 72 from LPL 1032:1034 arg1 kidney 1137:1142 head kidney 1132:1142 head kidney 1132:1142 We adopted quantitative real-time RT-PCR method to detect the mRNA expression of LPL of C. nasus in ten tissues including mesenteric adipose, liver, muscle, stomach, spleen, heart, head kidney, trunk kidney, gill and brain with β-actin as internal reference. 26877109 8 72 from LPL 1032:1034 arg1 adipose 1084:1090 mesenteric adipose 1073:1090 mesenteric adipose 1073:1090 We adopted quantitative real-time RT-PCR method to detect the mRNA expression of LPL of C. nasus in ten tissues including mesenteric adipose, liver, muscle, stomach, spleen, heart, head kidney, trunk kidney, gill and brain with β-actin as internal reference. 26877109 8 72 from LPL 1032:1034 arg1 stomach 1108:1114 stomach 1108:1114 stomach 1108:1114 We adopted quantitative real-time RT-PCR method to detect the mRNA expression of LPL of C. nasus in ten tissues including mesenteric adipose, liver, muscle, stomach, spleen, heart, head kidney, trunk kidney, gill and brain with β-actin as internal reference. 26877109 8 72 from LPL 1032:1034 arg1 brain 1168:1172 brain 1168:1172 brain 1168:1172 We adopted quantitative real-time RT-PCR method to detect the mRNA expression of LPL of C. nasus in ten tissues including mesenteric adipose, liver, muscle, stomach, spleen, heart, head kidney, trunk kidney, gill and brain with β-actin as internal reference. 26877109 8 72 from LPL 1032:1034 arg1 spleen 1117:1122 spleen 1117:1122 spleen 1117:1122 We adopted quantitative real-time RT-PCR method to detect the mRNA expression of LPL of C. nasus in ten tissues including mesenteric adipose, liver, muscle, stomach, spleen, heart, head kidney, trunk kidney, gill and brain with β-actin as internal reference. 26877109 8 72 from LPL 1032:1034 arg1 liver 1093:1097 liver 1093:1097 liver 1093:1097 We adopted quantitative real-time RT-PCR method to detect the mRNA expression of LPL of C. nasus in ten tissues including mesenteric adipose, liver, muscle, stomach, spleen, heart, head kidney, trunk kidney, gill and brain with β-actin as internal reference. 26877109 8 72 from LPL 1032:1034 arg1 tissues 1055:1061 ten tissues 1051:1061 ten tissues including mesenteric adipose 1051:1090 We adopted quantitative real-time RT-PCR method to detect the mRNA expression of LPL of C. nasus in ten tissues including mesenteric adipose, liver, muscle, stomach, spleen, heart, head kidney, trunk kidney, gill and brain with β-actin as internal reference. 26877109 8 72 from LPL 1032:1034 arg1 kidney 1151:1156 trunk kidney 1145:1156 trunk kidney 1145:1156 We adopted quantitative real-time RT-PCR method to detect the mRNA expression of LPL of C. nasus in ten tissues including mesenteric adipose, liver, muscle, stomach, spleen, heart, head kidney, trunk kidney, gill and brain with β-actin as internal reference. 26877109 7 73 link N-linked 881:888 arg1 sites 904:908 catalytic triad, N-linked glycosylation sites 864:908 sites 904:908 It had typical conserved domain of LPL protein containing catalytic triad, N-linked glycosylation sites and conserved heparin-binding site, etc. 26877109 8 74 theme RT-PCR 985:990 arg1 method 992:997 quantitative real-time RT-PCR method 962:997 quantitative real-time RT-PCR method 962:997 We adopted quantitative real-time RT-PCR method to detect the mRNA expression of LPL of C. nasus in ten tissues including mesenteric adipose, liver, muscle, stomach, spleen, heart, head kidney, trunk kidney, gill and brain with β-actin as internal reference. 26877109 7 75 theme triad 874:878 arg1 sites 904:908 catalytic triad, N-linked glycosylation sites 864:908 sites 904:908 It had typical conserved domain of LPL protein containing catalytic triad, N-linked glycosylation sites and conserved heparin-binding site, etc. 26877109 4 76 theme lipase 442:447 arg1 gene 449:452 lipoprotein lipase gene 430:452 lipoprotein lipase gene 430:452 To make further research on lipid metabolism of C. nasus, we cloned lipoprotein lipase gene with homologous cloning method. 26877109 7 77 contain had 809:811 arg2 domain 831:836 typical conserved domain 813:836 typical conserved domain of LPL protein containing catalytic triad, N-linked glycosylation sites and conserved heparin-binding site, etc 813:948 It had typical conserved domain of LPL protein containing catalytic triad, N-linked glycosylation sites and conserved heparin-binding site, etc. 26877109 7 77 contain had 809:811 arg1 It 806:807 It 806:807 It 806:807 It had typical conserved domain of LPL protein containing catalytic triad, N-linked glycosylation sites and conserved heparin-binding site, etc. 26877109 7 77 contain had 809:811 arg2 protein 845:851 LPL protein 841:851 LPL protein 841:851 It had typical conserved domain of LPL protein containing catalytic triad, N-linked glycosylation sites and conserved heparin-binding site, etc. 26877109 5 78 theme nasus 518:522 arg1 LPL 508:510 LPL 508:510 LPL of C. nasus 508:522 A full-length cDNA of LPL of C. nasus was cloned from liver which covered 3537 bp with a 1519 bp open reading frame encoding 505 deduced amino acids whose molecular mass was 57.5 kDa and theoretical isoelectric point was 7.58. 26877109 0 79 theme expression 22:31 arg1 analysis 33:40 expression analysis 22:40 expression analysis 22:40 Molecular cloning and expression analysis on LPL of Coilia nasus. 26877109 7 80 theme LPL 841:843 arg1 protein 845:851 LPL protein 841:851 LPL protein 841:851 It had typical conserved domain of LPL protein containing catalytic triad, N-linked glycosylation sites and conserved heparin-binding site, etc. 26877109 6 81 with similarity 746:755 arg1 sequence 779:786 the reported LPL sequence 762:786 the reported LPL sequence of other species 762:803 The deduced amino acids had high similarity with the reported LPL sequence of other species. 26877109 12 82 from research 1430:1437 arg1 cloning 1446:1452 cloning 1446:1452 cloning 1446:1452 The research on the cloning and differential expression of LPL of C. nasus will lay foundation for further research on lipid metabolism of C. nasus. 26877109 12 82 from research 1430:1437 arg1 expression 1471:1480 differential expression 1458:1480 differential expression 1458:1480 The research on the cloning and differential expression of LPL of C. nasus will lay foundation for further research on lipid metabolism of C. nasus. 26877109 12 83 theme differential 1458:1469 arg1 expression 1471:1480 differential expression 1458:1480 differential expression 1458:1480 The research on the cloning and differential expression of LPL of C. nasus will lay foundation for further research on lipid metabolism of C. nasus. 26877109 8 84 theme LPL 1032:1034 arg1 expression 1018:1027 the mRNA expression 1009:1027 the mRNA expression of LPL of C. nasus in ten tissues including mesenteric adipose, liver, muscle, stomach, spleen, heart, head kidney, trunk kidney, gill and brain 1009:1172 We adopted quantitative real-time RT-PCR method to detect the mRNA expression of LPL of C. nasus in ten tissues including mesenteric adipose, liver, muscle, stomach, spleen, heart, head kidney, trunk kidney, gill and brain with β-actin as internal reference. 26877109 6 85 theme reported 766:773 arg1 sequence 779:786 the reported LPL sequence 762:786 the reported LPL sequence of other species 762:803 The deduced amino acids had high similarity with the reported LPL sequence of other species. 26877109 7 86 theme conserved 821:829 arg1 protein 845:851 LPL protein 841:851 LPL protein 841:851 It had typical conserved domain of LPL protein containing catalytic triad, N-linked glycosylation sites and conserved heparin-binding site, etc. 26877109 7 86 theme conserved 821:829 arg1 domain 831:836 typical conserved domain 813:836 typical conserved domain of LPL protein containing catalytic triad, N-linked glycosylation sites and conserved heparin-binding site, etc 813:948 It had typical conserved domain of LPL protein containing catalytic triad, N-linked glycosylation sites and conserved heparin-binding site, etc. 26877109 2 87 theme resource 274:281 arg1 damage 283:288 its severe resource damage 263:288 its severe resource damage 263:288 At present, it has been on the "National Key Protective Species List" because of its severe resource damage. 26877109 6 88 theme high 741:744 arg1 similarity 746:755 high similarity 741:755 high similarity with the reported LPL sequence of other species 741:803 The deduced amino acids had high similarity with the reported LPL sequence of other species. 26600273 9 0 theme conserved 1670:1678 arg1 residues 1680:1687 these conserved residues 1664:1687 these conserved residues 1664:1687 Mutagenesis analysis of these conserved residues provides further information about the essentiality of many of these residues in catalysis. 26600273 2 1 theme glycans 398:404 arg1 biosynthesis 369:380 the biosynthesis 365:380 the biosynthesis of cell-surface glycans and glycoconjugates 365:424 These enzymes act at the membrane interface, forming the first membrane-associated intermediates in the biosynthesis of cell-surface glycans and glycoconjugates, including glycoproteins, glycolipids, and the peptidoglycan in bacteria. 26600273 7 2 theme sequences 1171:1179 arg1 pool 1157:1160 The pool 1153:1160 The pool of 15000 sequences that are analyzed 1153:1197 The pool of 15000 sequences that are analyzed include the PglC-like enzymes, as well as sequences from two other related PGTs that contain a "PglC-like" domain embedded in their larger structures (namely, the bifunctional PglB family, typified by PglB from Neisseria gonorrheae, and WbaP-like enzymes, typified by WbaP from Salmonella enterica). 26600273 5 3 link N-linked 776:783 arg1 glycoproteins 785:797 N-linked glycoproteins 776:797 N-linked glycoproteins 776:797 PglC, a PGT involved in the biosynthesis of N-linked glycoproteins in the enteropathogen Campylobacter jejuni, is representative of one of the structurally most simple members of the diverse family of small bacterial PGT enzymes. 26600273 4 4 theme single 694:699 arg1 helix 725:729 only a single predicted transmembrane helix 687:729 only a single predicted transmembrane helix 687:729 PGTs, such as MraY and WecA, are polytopic, while other families of uniquely prokaryotic enzymes have only a single predicted transmembrane helix. 26600273 1 5 theme soluble 201:207 arg1 diphosphate 226:236 a soluble sugar nucleotide diphosphate 199:236 a soluble sugar nucleotide diphosphate 199:236 Phosphoglycosyltransferases (PGTs) catalyze the transfer of a C1'-phosphosugar from a soluble sugar nucleotide diphosphate to a polyprenol phosphate. 26600273 4 6 theme transmembrane 711:723 arg1 helix 725:729 only a single predicted transmembrane helix 687:729 only a single predicted transmembrane helix 687:729 PGTs, such as MraY and WecA, are polytopic, while other families of uniquely prokaryotic enzymes have only a single predicted transmembrane helix. 26600273 10 7 theme enzymes 2038:2044 arg1 families 2006:2013 these families 2000:2013 these families of small bacterial PGT enzymes 2000:2044 Construction of a structural model of the cytosolic globular domain utilizing three-dimensional distance constraints, provided by conservation covariance analysis, provides additional insight into the catalytic core of these families of small bacterial PGT enzymes. 26600273 1 8 theme nucleotide 215:224 arg1 diphosphate 226:236 a soluble sugar nucleotide diphosphate 199:236 a soluble sugar nucleotide diphosphate 199:236 Phosphoglycosyltransferases (PGTs) catalyze the transfer of a C1'-phosphosugar from a soluble sugar nucleotide diphosphate to a polyprenol phosphate. 26600273 9 9 from essentiality 1728:1739 arg1 catalysis 1770:1778 catalysis 1770:1778 catalysis 1770:1778 Mutagenesis analysis of these conserved residues provides further information about the essentiality of many of these residues in catalysis. 26600273 4 10 theme enzymes 674:680 arg1 families 641:648 other families 635:648 other families of uniquely prokaryotic enzymes 635:680 PGTs, such as MraY and WecA, are polytopic, while other families of uniquely prokaryotic enzymes have only a single predicted transmembrane helix. 26600273 10 11 theme bacterial 2024:2032 arg1 enzymes 2038:2044 small bacterial PGT enzymes 2018:2044 small bacterial PGT enzymes 2018:2044 Construction of a structural model of the cytosolic globular domain utilizing three-dimensional distance constraints, provided by conservation covariance analysis, provides additional insight into the catalytic core of these families of small bacterial PGT enzymes. 26600273 2 12 theme first 322:326 arg1 glycolipids 452:462 glycolipids 452:462 glycolipids 452:462 These enzymes act at the membrane interface, forming the first membrane-associated intermediates in the biosynthesis of cell-surface glycans and glycoconjugates, including glycoproteins, glycolipids, and the peptidoglycan in bacteria. 26600273 2 12 theme first 322:326 arg1 intermediates 348:360 the first membrane-associated intermediates 318:360 the first membrane-associated intermediates 318:360 These enzymes act at the membrane interface, forming the first membrane-associated intermediates in the biosynthesis of cell-surface glycans and glycoconjugates, including glycoproteins, glycolipids, and the peptidoglycan in bacteria. 26600273 2 12 theme first 322:326 arg1 glycoproteins 437:449 glycoproteins 437:449 glycoproteins 437:449 These enzymes act at the membrane interface, forming the first membrane-associated intermediates in the biosynthesis of cell-surface glycans and glycoconjugates, including glycoproteins, glycolipids, and the peptidoglycan in bacteria. 26600273 2 12 theme first 322:326 arg1 peptidoglycan 473:485 the peptidoglycan 469:485 the peptidoglycan in bacteria 469:497 These enzymes act at the membrane interface, forming the first membrane-associated intermediates in the biosynthesis of cell-surface glycans and glycoconjugates, including glycoproteins, glycolipids, and the peptidoglycan in bacteria. 26600273 1 13 theme polyprenol 243:252 arg1 phosphate 254:262 a polyprenol phosphate 241:262 a polyprenol phosphate 241:262 Phosphoglycosyltransferases (PGTs) catalyze the transfer of a C1'-phosphosugar from a soluble sugar nucleotide diphosphate to a polyprenol phosphate. 26600273 9 14 theme residues 1758:1765 arg1 many 1744:1747 many 1744:1747 many 1744:1747 Mutagenesis analysis of these conserved residues provides further information about the essentiality of many of these residues in catalysis. 26600273 9 14 theme residues 1758:1765 arg1 residues 1758:1765 these residues 1752:1765 these residues 1752:1765 Mutagenesis analysis of these conserved residues provides further information about the essentiality of many of these residues in catalysis. 26600273 10 15 theme globular 1833:1840 arg1 domain 1842:1847 the cytosolic globular domain 1819:1847 the cytosolic globular domain utilizing three-dimensional distance constraints 1819:1896 Construction of a structural model of the cytosolic globular domain utilizing three-dimensional distance constraints, provided by conservation covariance analysis, provides additional insight into the catalytic core of these families of small bacterial PGT enzymes. 26600273 1 16 from diphosphate 226:236 arg1 transfer 163:170 the transfer 159:170 the transfer of a C1'-phosphosugar from a soluble sugar nucleotide diphosphate to a polyprenol phosphate 159:262 Phosphoglycosyltransferases (PGTs) catalyze the transfer of a C1'-phosphosugar from a soluble sugar nucleotide diphosphate to a polyprenol phosphate. 26600273 1 16 from diphosphate 226:236 arg1 C1'-phosphosugar 177:192 a C1'-phosphosugar 175:192 a C1'-phosphosugar from a soluble sugar nucleotide diphosphate 175:236 Phosphoglycosyltransferases (PGTs) catalyze the transfer of a C1'-phosphosugar from a soluble sugar nucleotide diphosphate to a polyprenol phosphate. 26600273 5 17 theme enzymes 953:959 arg1 family 923:928 the diverse family 911:928 the diverse family of small bacterial PGT enzymes 911:959 PglC, a PGT involved in the biosynthesis of N-linked glycoproteins in the enteropathogen Campylobacter jejuni, is representative of one of the structurally most simple members of the diverse family of small bacterial PGT enzymes. 26600273 7 18 from gonorrheae 1420:1429 arg1 PglB 1400:1403 PglB 1400:1403 PglB from Neisseria gonorrheae, and WbaP-like enzymes 1400:1452 The pool of 15000 sequences that are analyzed include the PglC-like enzymes, as well as sequences from two other related PGTs that contain a "PglC-like" domain embedded in their larger structures (namely, the bifunctional PglB family, typified by PglB from Neisseria gonorrheae, and WbaP-like enzymes, typified by WbaP from Salmonella enterica). 26600273 7 19 theme PglB 1375:1378 arg1 family 1380:1385 the bifunctional PglB family 1358:1385 the bifunctional PglB family 1358:1385 The pool of 15000 sequences that are analyzed include the PglC-like enzymes, as well as sequences from two other related PGTs that contain a "PglC-like" domain embedded in their larger structures (namely, the bifunctional PglB family, typified by PglB from Neisseria gonorrheae, and WbaP-like enzymes, typified by WbaP from Salmonella enterica). 26600273 5 20 from biosynthesis 760:771 arg1 jejuni 835:840 the enteropathogen Campylobacter jejuni 802:840 the enteropathogen Campylobacter jejuni 802:840 PglC, a PGT involved in the biosynthesis of N-linked glycoproteins in the enteropathogen Campylobacter jejuni, is representative of one of the structurally most simple members of the diverse family of small bacterial PGT enzymes. 26600273 10 21 theme distance 1877:1884 arg1 constraints 1886:1896 three-dimensional distance constraints 1859:1896 three-dimensional distance constraints 1859:1896 Construction of a structural model of the cytosolic globular domain utilizing three-dimensional distance constraints, provided by conservation covariance analysis, provides additional insight into the catalytic core of these families of small bacterial PGT enzymes. 26600273 7 22 from enzymes 1446:1452 arg1 PglB 1400:1403 PglB 1400:1403 PglB from Neisseria gonorrheae, and WbaP-like enzymes 1400:1452 The pool of 15000 sequences that are analyzed include the PglC-like enzymes, as well as sequences from two other related PGTs that contain a "PglC-like" domain embedded in their larger structures (namely, the bifunctional PglB family, typified by PglB from Neisseria gonorrheae, and WbaP-like enzymes, typified by WbaP from Salmonella enterica). 26600273 6 23 theme model 1071:1075 arg1 building 1077:1084 geometry- and homology-based model building 1042:1084 geometry- and homology-based model building 1042:1084 Herein, we apply bioinformatics and covariance-weighted distance constraints in geometry- and homology-based model building, together with mutational analysis, to investigate monotopic PGTs. 26600273 0 24 from Covariance 17:26 arg1 Phosphoglycosyltransferases 47:73 Small Bacterial Phosphoglycosyltransferases 31:73 Small Bacterial Phosphoglycosyltransferases 31:73 Conservation and Covariance in Small Bacterial Phosphoglycosyltransferases Identify the Functional Catalytic Core. 26600273 0 25 theme Catalytic 99:107 arg1 Core 109:112 the Functional Catalytic Core 84:112 the Functional Catalytic Core 84:112 Conservation and Covariance in Small Bacterial Phosphoglycosyltransferases Identify the Functional Catalytic Core. 26600273 5 26 theme bacterial 939:947 arg1 enzymes 953:959 small bacterial PGT enzymes 933:959 small bacterial PGT enzymes 933:959 PglC, a PGT involved in the biosynthesis of N-linked glycoproteins in the enteropathogen Campylobacter jejuni, is representative of one of the structurally most simple members of the diverse family of small bacterial PGT enzymes. 26600273 0 27 from Conservation 0:11 arg1 Phosphoglycosyltransferases 47:73 Small Bacterial Phosphoglycosyltransferases 31:73 Small Bacterial Phosphoglycosyltransferases 31:73 Conservation and Covariance in Small Bacterial Phosphoglycosyltransferases Identify the Functional Catalytic Core. 26600273 5 28 theme N-linked 776:783 arg1 glycoproteins 785:797 N-linked glycoproteins 776:797 N-linked glycoproteins 776:797 PglC, a PGT involved in the biosynthesis of N-linked glycoproteins in the enteropathogen Campylobacter jejuni, is representative of one of the structurally most simple members of the diverse family of small bacterial PGT enzymes. 26600273 0 29 theme Bacterial 37:45 arg1 Phosphoglycosyltransferases 47:73 Small Bacterial Phosphoglycosyltransferases 31:73 Small Bacterial Phosphoglycosyltransferases 31:73 Conservation and Covariance in Small Bacterial Phosphoglycosyltransferases Identify the Functional Catalytic Core. 26600273 7 30 theme bifunctional 1362:1373 arg1 family 1380:1385 the bifunctional PglB family 1358:1385 the bifunctional PglB family 1358:1385 The pool of 15000 sequences that are analyzed include the PglC-like enzymes, as well as sequences from two other related PGTs that contain a "PglC-like" domain embedded in their larger structures (namely, the bifunctional PglB family, typified by PglB from Neisseria gonorrheae, and WbaP-like enzymes, typified by WbaP from Salmonella enterica). 26600273 0 31 theme Functional 88:97 arg1 Core 109:112 the Functional Catalytic Core 84:112 the Functional Catalytic Core 84:112 Conservation and Covariance in Small Bacterial Phosphoglycosyltransferases Identify the Functional Catalytic Core. 26600273 8 32 theme key 1566:1568 arg1 residues 1570:1577 key residues 1566:1577 key residues conserved across all three families of small bacterial PGTs 1566:1637 Including these two subfamilies of PGTs in the analysis highlights key residues conserved across all three families of small bacterial PGTs. 26600273 10 33 theme covariance 1924:1933 arg1 analysis 1935:1942 conservation covariance analysis 1911:1942 conservation covariance analysis 1911:1942 Construction of a structural model of the cytosolic globular domain utilizing three-dimensional distance constraints, provided by conservation covariance analysis, provides additional insight into the catalytic core of these families of small bacterial PGT enzymes. 26600273 0 34 theme Small 31:35 arg1 Phosphoglycosyltransferases 47:73 Small Bacterial Phosphoglycosyltransferases 31:73 Small Bacterial Phosphoglycosyltransferases 31:73 Conservation and Covariance in Small Bacterial Phosphoglycosyltransferases Identify the Functional Catalytic Core. 26600273 7 35 theme PglC-like 1211:1219 arg1 enzymes 1221:1227 the PglC-like enzymes 1207:1227 the PglC-like enzymes 1207:1227 The pool of 15000 sequences that are analyzed include the PglC-like enzymes, as well as sequences from two other related PGTs that contain a "PglC-like" domain embedded in their larger structures (namely, the bifunctional PglB family, typified by PglB from Neisseria gonorrheae, and WbaP-like enzymes, typified by WbaP from Salmonella enterica). 26600273 2 36 from glycoproteins 437:449 arg1 bacteria 490:497 bacteria 490:497 bacteria 490:497 These enzymes act at the membrane interface, forming the first membrane-associated intermediates in the biosynthesis of cell-surface glycans and glycoconjugates, including glycoproteins, glycolipids, and the peptidoglycan in bacteria. 26600273 7 37 theme larger 1331:1336 arg1 structures 1338:1347 their larger structures 1325:1347 their larger structures 1325:1347 The pool of 15000 sequences that are analyzed include the PglC-like enzymes, as well as sequences from two other related PGTs that contain a "PglC-like" domain embedded in their larger structures (namely, the bifunctional PglB family, typified by PglB from Neisseria gonorrheae, and WbaP-like enzymes, typified by WbaP from Salmonella enterica). 26600273 2 38 theme cell-surface 385:396 arg1 glycans 398:404 cell-surface glycans 385:404 cell-surface glycans 385:404 These enzymes act at the membrane interface, forming the first membrane-associated intermediates in the biosynthesis of cell-surface glycans and glycoconjugates, including glycoproteins, glycolipids, and the peptidoglycan in bacteria. 26600273 7 39 from structures 1338:1347 arg1 embedded 1313:1320 embedded 1313:1320 embedded 1313:1320 The pool of 15000 sequences that are analyzed include the PglC-like enzymes, as well as sequences from two other related PGTs that contain a "PglC-like" domain embedded in their larger structures (namely, the bifunctional PglB family, typified by PglB from Neisseria gonorrheae, and WbaP-like enzymes, typified by WbaP from Salmonella enterica). 26600273 10 40 theme additional 1954:1963 arg1 insight 1965:1971 additional insight 1954:1971 additional insight into the catalytic core of these families of small bacterial PGT enzymes 1954:2044 Construction of a structural model of the cytosolic globular domain utilizing three-dimensional distance constraints, provided by conservation covariance analysis, provides additional insight into the catalytic core of these families of small bacterial PGT enzymes. 26600273 8 41 theme small 1618:1622 arg1 PGTs 1634:1637 small bacterial PGTs 1618:1637 small bacterial PGTs 1618:1637 Including these two subfamilies of PGTs in the analysis highlights key residues conserved across all three families of small bacterial PGTs. 26600273 2 42 from peptidoglycan 473:485 arg1 bacteria 490:497 bacteria 490:497 bacteria 490:497 These enzymes act at the membrane interface, forming the first membrane-associated intermediates in the biosynthesis of cell-surface glycans and glycoconjugates, including glycoproteins, glycolipids, and the peptidoglycan in bacteria. 26600273 7 43 theme PglC-like 1295:1303 arg1 domain 1306:1311 a "PglC-like" domain 1292:1311 a "PglC-like" domain embedded in their larger structures 1292:1347 The pool of 15000 sequences that are analyzed include the PglC-like enzymes, as well as sequences from two other related PGTs that contain a "PglC-like" domain embedded in their larger structures (namely, the bifunctional PglB family, typified by PglB from Neisseria gonorrheae, and WbaP-like enzymes, typified by WbaP from Salmonella enterica). 26600273 8 44 theme PGTs 1634:1637 arg1 families 1606:1613 all three families 1596:1613 all three families of small bacterial PGTs 1596:1637 Including these two subfamilies of PGTs in the analysis highlights key residues conserved across all three families of small bacterial PGTs. 26600273 10 45 theme catalytic 1982:1990 arg1 core 1992:1995 the catalytic core 1978:1995 the catalytic core of these families of small bacterial PGT enzymes 1978:2044 Construction of a structural model of the cytosolic globular domain utilizing three-dimensional distance constraints, provided by conservation covariance analysis, provides additional insight into the catalytic core of these families of small bacterial PGT enzymes. 26600273 9 46 theme residues 1680:1687 arg1 analysis 1652:1659 Mutagenesis analysis 1640:1659 Mutagenesis analysis of these conserved residues 1640:1687 Mutagenesis analysis of these conserved residues provides further information about the essentiality of many of these residues in catalysis. 26600273 10 47 theme structural 1799:1808 arg1 model 1810:1814 a structural model 1797:1814 a structural model of the cytosolic globular domain utilizing three-dimensional distance constraints 1797:1896 Construction of a structural model of the cytosolic globular domain utilizing three-dimensional distance constraints, provided by conservation covariance analysis, provides additional insight into the catalytic core of these families of small bacterial PGT enzymes. 26600273 9 48 theme further 1698:1704 arg1 information 1706:1716 further information 1698:1716 further information about the essentiality of many of these residues in catalysis 1698:1778 Mutagenesis analysis of these conserved residues provides further information about the essentiality of many of these residues in catalysis. 26600273 5 49 theme small 933:937 arg1 enzymes 953:959 small bacterial PGT enzymes 933:959 small bacterial PGT enzymes 933:959 PglC, a PGT involved in the biosynthesis of N-linked glycoproteins in the enteropathogen Campylobacter jejuni, is representative of one of the structurally most simple members of the diverse family of small bacterial PGT enzymes. 26600273 10 50 theme families 2006:2013 arg1 core 1992:1995 the catalytic core 1978:1995 the catalytic core of these families of small bacterial PGT enzymes 1978:2044 Construction of a structural model of the cytosolic globular domain utilizing three-dimensional distance constraints, provided by conservation covariance analysis, provides additional insight into the catalytic core of these families of small bacterial PGT enzymes. 26600273 5 51 theme members 900:906 arg1 one 864:866 one 864:866 one 864:866 PglC, a PGT involved in the biosynthesis of N-linked glycoproteins in the enteropathogen Campylobacter jejuni, is representative of one of the structurally most simple members of the diverse family of small bacterial PGT enzymes. 26600273 5 51 theme members 900:906 arg1 members 900:906 the structurally most simple members 871:906 the structurally most simple members of the diverse family of small bacterial PGT enzymes 871:959 PglC, a PGT involved in the biosynthesis of N-linked glycoproteins in the enteropathogen Campylobacter jejuni, is representative of one of the structurally most simple members of the diverse family of small bacterial PGT enzymes. 26600273 5 52 theme enteropathogen 806:819 arg1 jejuni 835:840 the enteropathogen Campylobacter jejuni 802:840 the enteropathogen Campylobacter jejuni 802:840 PglC, a PGT involved in the biosynthesis of N-linked glycoproteins in the enteropathogen Campylobacter jejuni, is representative of one of the structurally most simple members of the diverse family of small bacterial PGT enzymes. 26600273 7 53 theme related 1266:1272 arg1 PGTs 1274:1277 two other related PGTs 1256:1277 two other related PGTs that contain a "PglC-like" domain embedded in their larger structures (namely, the bifunctional PglB family, typified by PglB from Neisseria gonorrheae, and WbaP-like enzymes, typified by WbaP from Salmonella enterica) 1256:1496 The pool of 15000 sequences that are analyzed include the PglC-like enzymes, as well as sequences from two other related PGTs that contain a "PglC-like" domain embedded in their larger structures (namely, the bifunctional PglB family, typified by PglB from Neisseria gonorrheae, and WbaP-like enzymes, typified by WbaP from Salmonella enterica). 26600273 10 54 theme cytosolic 1823:1831 arg1 domain 1842:1847 the cytosolic globular domain 1819:1847 the cytosolic globular domain utilizing three-dimensional distance constraints 1819:1896 Construction of a structural model of the cytosolic globular domain utilizing three-dimensional distance constraints, provided by conservation covariance analysis, provides additional insight into the catalytic core of these families of small bacterial PGT enzymes. 26600273 1 55 theme sugar 209:213 arg1 diphosphate 226:236 a soluble sugar nucleotide diphosphate 199:236 a soluble sugar nucleotide diphosphate 199:236 Phosphoglycosyltransferases (PGTs) catalyze the transfer of a C1'-phosphosugar from a soluble sugar nucleotide diphosphate to a polyprenol phosphate. 26600273 7 56 from embedded 1313:1320 arg1 structures 1338:1347 their larger structures 1325:1347 their larger structures 1325:1347 The pool of 15000 sequences that are analyzed include the PglC-like enzymes, as well as sequences from two other related PGTs that contain a "PglC-like" domain embedded in their larger structures (namely, the bifunctional PglB family, typified by PglB from Neisseria gonorrheae, and WbaP-like enzymes, typified by WbaP from Salmonella enterica). 26600273 7 57 theme WbaP-like 1436:1444 arg1 enzymes 1446:1452 WbaP-like enzymes 1436:1452 WbaP-like enzymes 1436:1452 The pool of 15000 sequences that are analyzed include the PglC-like enzymes, as well as sequences from two other related PGTs that contain a "PglC-like" domain embedded in their larger structures (namely, the bifunctional PglB family, typified by PglB from Neisseria gonorrheae, and WbaP-like enzymes, typified by WbaP from Salmonella enterica). 26600273 4 58 theme predicted 701:709 arg1 helix 725:729 only a single predicted transmembrane helix 687:729 only a single predicted transmembrane helix 687:729 PGTs, such as MraY and WecA, are polytopic, while other families of uniquely prokaryotic enzymes have only a single predicted transmembrane helix. 26600273 10 59 theme PGT 2034:2036 arg1 enzymes 2038:2044 small bacterial PGT enzymes 2018:2044 small bacterial PGT enzymes 2018:2044 Construction of a structural model of the cytosolic globular domain utilizing three-dimensional distance constraints, provided by conservation covariance analysis, provides additional insight into the catalytic core of these families of small bacterial PGT enzymes. 26600273 2 60 theme membrane-associated 328:346 arg1 glycolipids 452:462 glycolipids 452:462 glycolipids 452:462 These enzymes act at the membrane interface, forming the first membrane-associated intermediates in the biosynthesis of cell-surface glycans and glycoconjugates, including glycoproteins, glycolipids, and the peptidoglycan in bacteria. 26600273 2 60 theme membrane-associated 328:346 arg1 intermediates 348:360 the first membrane-associated intermediates 318:360 the first membrane-associated intermediates 318:360 These enzymes act at the membrane interface, forming the first membrane-associated intermediates in the biosynthesis of cell-surface glycans and glycoconjugates, including glycoproteins, glycolipids, and the peptidoglycan in bacteria. 26600273 2 60 theme membrane-associated 328:346 arg1 glycoproteins 437:449 glycoproteins 437:449 glycoproteins 437:449 These enzymes act at the membrane interface, forming the first membrane-associated intermediates in the biosynthesis of cell-surface glycans and glycoconjugates, including glycoproteins, glycolipids, and the peptidoglycan in bacteria. 26600273 2 60 theme membrane-associated 328:346 arg1 peptidoglycan 473:485 the peptidoglycan 469:485 the peptidoglycan in bacteria 469:497 These enzymes act at the membrane interface, forming the first membrane-associated intermediates in the biosynthesis of cell-surface glycans and glycoconjugates, including glycoproteins, glycolipids, and the peptidoglycan in bacteria. 26600273 7 61 from enterica 1488:1495 arg1 WbaP 1467:1470 WbaP 1467:1470 WbaP from Salmonella enterica 1467:1495 The pool of 15000 sequences that are analyzed include the PglC-like enzymes, as well as sequences from two other related PGTs that contain a "PglC-like" domain embedded in their larger structures (namely, the bifunctional PglB family, typified by PglB from Neisseria gonorrheae, and WbaP-like enzymes, typified by WbaP from Salmonella enterica). 26600273 6 62 theme covariance-weighted 998:1016 arg1 constraints 1027:1037 covariance-weighted distance constraints 998:1037 covariance-weighted distance constraints 998:1037 Herein, we apply bioinformatics and covariance-weighted distance constraints in geometry- and homology-based model building, together with mutational analysis, to investigate monotopic PGTs. 26600273 2 63 from glycolipids 452:462 arg1 bacteria 490:497 bacteria 490:497 bacteria 490:497 These enzymes act at the membrane interface, forming the first membrane-associated intermediates in the biosynthesis of cell-surface glycans and glycoconjugates, including glycoproteins, glycolipids, and the peptidoglycan in bacteria. 26600273 4 64 theme prokaryotic 662:672 arg1 enzymes 674:680 uniquely prokaryotic enzymes 653:680 uniquely prokaryotic enzymes 653:680 PGTs, such as MraY and WecA, are polytopic, while other families of uniquely prokaryotic enzymes have only a single predicted transmembrane helix. 26600273 10 65 theme small 2018:2022 arg1 enzymes 2038:2044 small bacterial PGT enzymes 2018:2044 small bacterial PGT enzymes 2018:2044 Construction of a structural model of the cytosolic globular domain utilizing three-dimensional distance constraints, provided by conservation covariance analysis, provides additional insight into the catalytic core of these families of small bacterial PGT enzymes. 26600273 10 66 theme three-dimensional 1859:1875 arg1 constraints 1886:1896 three-dimensional distance constraints 1859:1896 three-dimensional distance constraints 1859:1896 Construction of a structural model of the cytosolic globular domain utilizing three-dimensional distance constraints, provided by conservation covariance analysis, provides additional insight into the catalytic core of these families of small bacterial PGT enzymes. 26600273 5 67 theme diverse 915:921 arg1 family 923:928 the diverse family 911:928 the diverse family of small bacterial PGT enzymes 911:959 PglC, a PGT involved in the biosynthesis of N-linked glycoproteins in the enteropathogen Campylobacter jejuni, is representative of one of the structurally most simple members of the diverse family of small bacterial PGT enzymes. 26600273 6 68 theme distance 1018:1025 arg1 constraints 1027:1037 covariance-weighted distance constraints 998:1037 covariance-weighted distance constraints 998:1037 Herein, we apply bioinformatics and covariance-weighted distance constraints in geometry- and homology-based model building, together with mutational analysis, to investigate monotopic PGTs. 26600273 10 69 theme domain 1842:1847 arg1 model 1810:1814 a structural model 1797:1814 a structural model of the cytosolic globular domain utilizing three-dimensional distance constraints 1797:1896 Construction of a structural model of the cytosolic globular domain utilizing three-dimensional distance constraints, provided by conservation covariance analysis, provides additional insight into the catalytic core of these families of small bacterial PGT enzymes. 26600273 5 70 theme PGT 949:951 arg1 enzymes 953:959 small bacterial PGT enzymes 933:959 small bacterial PGT enzymes 933:959 PglC, a PGT involved in the biosynthesis of N-linked glycoproteins in the enteropathogen Campylobacter jejuni, is representative of one of the structurally most simple members of the diverse family of small bacterial PGT enzymes. 26600273 10 71 theme model 1810:1814 arg1 Construction 1781:1792 Construction 1781:1792 Construction 1781:1792 Construction of a structural model of the cytosolic globular domain utilizing three-dimensional distance constraints, provided by conservation covariance analysis, provides additional insight into the catalytic core of these families of small bacterial PGT enzymes. 26600273 2 72 theme membrane 290:297 arg1 interface 299:307 the membrane interface 286:307 the membrane interface 286:307 These enzymes act at the membrane interface, forming the first membrane-associated intermediates in the biosynthesis of cell-surface glycans and glycoconjugates, including glycoproteins, glycolipids, and the peptidoglycan in bacteria. 26600273 7 73 from PGTs 1274:1277 arg1 sequences 1241:1249 sequences 1241:1249 sequences from two other related PGTs that contain a "PglC-like" domain embedded in their larger structures (namely, the bifunctional PglB family, typified by PglB from Neisseria gonorrheae, and WbaP-like enzymes, typified by WbaP from Salmonella enterica) 1241:1496 The pool of 15000 sequences that are analyzed include the PglC-like enzymes, as well as sequences from two other related PGTs that contain a "PglC-like" domain embedded in their larger structures (namely, the bifunctional PglB family, typified by PglB from Neisseria gonorrheae, and WbaP-like enzymes, typified by WbaP from Salmonella enterica). 26600273 7 73 from PGTs 1274:1277 arg1 enzymes 1221:1227 the PglC-like enzymes 1207:1227 the PglC-like enzymes 1207:1227 The pool of 15000 sequences that are analyzed include the PglC-like enzymes, as well as sequences from two other related PGTs that contain a "PglC-like" domain embedded in their larger structures (namely, the bifunctional PglB family, typified by PglB from Neisseria gonorrheae, and WbaP-like enzymes, typified by WbaP from Salmonella enterica). 26600273 5 74 theme glycoproteins 785:797 arg1 biosynthesis 760:771 the biosynthesis 756:771 the biosynthesis of N-linked glycoproteins in the enteropathogen Campylobacter jejuni 756:840 PglC, a PGT involved in the biosynthesis of N-linked glycoproteins in the enteropathogen Campylobacter jejuni, is representative of one of the structurally most simple members of the diverse family of small bacterial PGT enzymes. 26600273 5 75 theme family 923:928 arg1 members 900:906 the structurally most simple members 871:906 the structurally most simple members of the diverse family of small bacterial PGT enzymes 871:959 PglC, a PGT involved in the biosynthesis of N-linked glycoproteins in the enteropathogen Campylobacter jejuni, is representative of one of the structurally most simple members of the diverse family of small bacterial PGT enzymes. 26600273 7 76 theme other 1260:1264 arg1 PGTs 1274:1277 two other related PGTs 1256:1277 two other related PGTs that contain a "PglC-like" domain embedded in their larger structures (namely, the bifunctional PglB family, typified by PglB from Neisseria gonorrheae, and WbaP-like enzymes, typified by WbaP from Salmonella enterica) 1256:1496 The pool of 15000 sequences that are analyzed include the PglC-like enzymes, as well as sequences from two other related PGTs that contain a "PglC-like" domain embedded in their larger structures (namely, the bifunctional PglB family, typified by PglB from Neisseria gonorrheae, and WbaP-like enzymes, typified by WbaP from Salmonella enterica). 26600273 7 77 contain contain 1284:1290 arg2 domain 1306:1311 a "PglC-like" domain 1292:1311 a "PglC-like" domain embedded in their larger structures 1292:1347 The pool of 15000 sequences that are analyzed include the PglC-like enzymes, as well as sequences from two other related PGTs that contain a "PglC-like" domain embedded in their larger structures (namely, the bifunctional PglB family, typified by PglB from Neisseria gonorrheae, and WbaP-like enzymes, typified by WbaP from Salmonella enterica). 26600273 7 77 contain contain 1284:1290 arg1 PGTs 1274:1277 two other related PGTs 1256:1277 two other related PGTs that contain a "PglC-like" domain embedded in their larger structures (namely, the bifunctional PglB family, typified by PglB from Neisseria gonorrheae, and WbaP-like enzymes, typified by WbaP from Salmonella enterica) 1256:1496 The pool of 15000 sequences that are analyzed include the PglC-like enzymes, as well as sequences from two other related PGTs that contain a "PglC-like" domain embedded in their larger structures (namely, the bifunctional PglB family, typified by PglB from Neisseria gonorrheae, and WbaP-like enzymes, typified by WbaP from Salmonella enterica). 26600273 1 78 theme C1'-phosphosugar 177:192 arg1 transfer 163:170 the transfer 159:170 the transfer of a C1'-phosphosugar from a soluble sugar nucleotide diphosphate to a polyprenol phosphate 159:262 Phosphoglycosyltransferases (PGTs) catalyze the transfer of a C1'-phosphosugar from a soluble sugar nucleotide diphosphate to a polyprenol phosphate. 26600273 6 79 theme homology-based 1056:1069 arg1 building 1077:1084 geometry- and homology-based model building 1042:1084 geometry- and homology-based model building 1042:1084 Herein, we apply bioinformatics and covariance-weighted distance constraints in geometry- and homology-based model building, together with mutational analysis, to investigate monotopic PGTs. 26600273 9 80 theme many 1744:1747 arg1 essentiality 1728:1739 the essentiality 1724:1739 the essentiality of many of these residues in catalysis 1724:1778 Mutagenesis analysis of these conserved residues provides further information about the essentiality of many of these residues in catalysis. 26600273 8 81 theme PGTs 1534:1537 arg1 subfamilies 1519:1529 these two subfamilies 1509:1529 these two subfamilies of PGTs 1509:1537 Including these two subfamilies of PGTs in the analysis highlights key residues conserved across all three families of small bacterial PGTs. 26600273 2 82 from intermediates 348:360 arg1 biosynthesis 369:380 the biosynthesis 365:380 the biosynthesis of cell-surface glycans and glycoconjugates 365:424 These enzymes act at the membrane interface, forming the first membrane-associated intermediates in the biosynthesis of cell-surface glycans and glycoconjugates, including glycoproteins, glycolipids, and the peptidoglycan in bacteria. 26600273 6 83 theme geometry- 1042:1050 arg1 building 1077:1084 geometry- and homology-based model building 1042:1084 geometry- and homology-based model building 1042:1084 Herein, we apply bioinformatics and covariance-weighted distance constraints in geometry- and homology-based model building, together with mutational analysis, to investigate monotopic PGTs. 26600273 5 84 gly glycoproteins 785:797 arg1 glycoproteins 785:797 N-linked glycoproteins 776:797 N-linked glycoproteins 776:797 PglC, a PGT involved in the biosynthesis of N-linked glycoproteins in the enteropathogen Campylobacter jejuni, is representative of one of the structurally most simple members of the diverse family of small bacterial PGT enzymes. 26600273 4 85 theme other 635:639 arg1 families 641:648 other families 635:648 other families of uniquely prokaryotic enzymes 635:680 PGTs, such as MraY and WecA, are polytopic, while other families of uniquely prokaryotic enzymes have only a single predicted transmembrane helix. 26600273 1 86 from transfer 163:170 arg1 diphosphate 226:236 a soluble sugar nucleotide diphosphate 199:236 a soluble sugar nucleotide diphosphate 199:236 Phosphoglycosyltransferases (PGTs) catalyze the transfer of a C1'-phosphosugar from a soluble sugar nucleotide diphosphate to a polyprenol phosphate. 26600273 2 87 gly glycoproteins 437:449 arg1 glycoproteins 437:449 glycoproteins 437:449 glycoproteins 437:449 These enzymes act at the membrane interface, forming the first membrane-associated intermediates in the biosynthesis of cell-surface glycans and glycoconjugates, including glycoproteins, glycolipids, and the peptidoglycan in bacteria. 26600273 5 88 theme one 864:866 arg1 representative 846:859 representative 846:859 representative 846:859 PglC, a PGT involved in the biosynthesis of N-linked glycoproteins in the enteropathogen Campylobacter jejuni, is representative of one of the structurally most simple members of the diverse family of small bacterial PGT enzymes. 26600273 4 89 contain have 682:685 arg1 families 641:648 other families 635:648 other families of uniquely prokaryotic enzymes 635:680 PGTs, such as MraY and WecA, are polytopic, while other families of uniquely prokaryotic enzymes have only a single predicted transmembrane helix. 26600273 4 89 contain have 682:685 arg2 helix 725:729 only a single predicted transmembrane helix 687:729 only a single predicted transmembrane helix 687:729 PGTs, such as MraY and WecA, are polytopic, while other families of uniquely prokaryotic enzymes have only a single predicted transmembrane helix. 26600273 5 90 theme Campylobacter 821:833 arg1 jejuni 835:840 the enteropathogen Campylobacter jejuni 802:840 the enteropathogen Campylobacter jejuni 802:840 PglC, a PGT involved in the biosynthesis of N-linked glycoproteins in the enteropathogen Campylobacter jejuni, is representative of one of the structurally most simple members of the diverse family of small bacterial PGT enzymes. 26600273 6 91 theme mutational 1101:1110 arg1 analysis 1112:1119 mutational analysis 1101:1119 mutational analysis 1101:1119 Herein, we apply bioinformatics and covariance-weighted distance constraints in geometry- and homology-based model building, together with mutational analysis, to investigate monotopic PGTs. 26600273 10 92 theme conservation 1911:1922 arg1 analysis 1935:1942 conservation covariance analysis 1911:1942 conservation covariance analysis 1911:1942 Construction of a structural model of the cytosolic globular domain utilizing three-dimensional distance constraints, provided by conservation covariance analysis, provides additional insight into the catalytic core of these families of small bacterial PGT enzymes. 26600273 7 93 theme embedded 1313:1320 arg1 domain 1306:1311 a "PglC-like" domain 1292:1311 a "PglC-like" domain embedded in their larger structures 1292:1347 The pool of 15000 sequences that are analyzed include the PglC-like enzymes, as well as sequences from two other related PGTs that contain a "PglC-like" domain embedded in their larger structures (namely, the bifunctional PglB family, typified by PglB from Neisseria gonorrheae, and WbaP-like enzymes, typified by WbaP from Salmonella enterica). 26600273 3 94 theme substrate 562:570 arg1 preferences 572:582 their substrate preferences 556:582 their substrate preferences 556:582 PGTs vary greatly in both their membrane topologies and their substrate preferences. 26600273 9 95 theme Mutagenesis 1640:1650 arg1 analysis 1652:1659 Mutagenesis analysis 1640:1659 Mutagenesis analysis of these conserved residues 1640:1687 Mutagenesis analysis of these conserved residues provides further information about the essentiality of many of these residues in catalysis. 26600273 7 96 theme " 1304:1304 arg1 domain 1306:1311 a "PglC-like" domain 1292:1311 a "PglC-like" domain embedded in their larger structures 1292:1347 The pool of 15000 sequences that are analyzed include the PglC-like enzymes, as well as sequences from two other related PGTs that contain a "PglC-like" domain embedded in their larger structures (namely, the bifunctional PglB family, typified by PglB from Neisseria gonorrheae, and WbaP-like enzymes, typified by WbaP from Salmonella enterica). 26600273 8 97 theme bacterial 1624:1632 arg1 PGTs 1634:1637 small bacterial PGTs 1618:1637 small bacterial PGTs 1618:1637 Including these two subfamilies of PGTs in the analysis highlights key residues conserved across all three families of small bacterial PGTs. 26600273 3 98 theme membrane 532:539 arg1 topologies 541:550 their membrane topologies 526:550 their membrane topologies 526:550 PGTs vary greatly in both their membrane topologies and their substrate preferences. 26600273 5 99 theme simple 893:898 arg1 members 900:906 the structurally most simple members 871:906 the structurally most simple members of the diverse family of small bacterial PGT enzymes 871:959 PglC, a PGT involved in the biosynthesis of N-linked glycoproteins in the enteropathogen Campylobacter jejuni, is representative of one of the structurally most simple members of the diverse family of small bacterial PGT enzymes. 26600273 6 100 theme monotopic 1137:1145 arg1 PGTs 1147:1150 monotopic PGTs 1137:1150 monotopic PGTs 1137:1150 Herein, we apply bioinformatics and covariance-weighted distance constraints in geometry- and homology-based model building, together with mutational analysis, to investigate monotopic PGTs. 26600273 2 101 theme glycoconjugates 410:424 arg1 biosynthesis 369:380 the biosynthesis 365:380 the biosynthesis of cell-surface glycans and glycoconjugates 365:424 These enzymes act at the membrane interface, forming the first membrane-associated intermediates in the biosynthesis of cell-surface glycans and glycoconjugates, including glycoproteins, glycolipids, and the peptidoglycan in bacteria. 25087952 4 0 theme O-GlcNAcylation 818:832 arg1 levels 845:850 O-GlcNAcylation and Hsp 70 levels 818:850 O-GlcNAcylation and Hsp 70 levels in HeLa cells 818:864 The exposure to arsenite increased O-GlcNAcylation and Hsp 70 levels in HeLa cells. 25087952 8 1 theme mRNA 1377:1380 arg1 expression 1382:1391 Hsp 70 mRNA expression 1370:1391 Hsp 70 mRNA expression 1370:1391 Finally, Hsp 70 mRNA expression was induced by arsenite, whereas the addition of PUGNAc slightly suppressed its induction. 25087952 3 2 theme amino 498:502 arg1 PUGNAc 524:529 PUGNAc 524:529 PUGNAc 524:529 We used O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc), an inhibitor of O-GlcNAcase, and glucosamine (GlcN), an enhancer of the hexosamine biosynthesis pathway, or O-GlcNAc transferase (OGT) short interfering RNA (siRNA) to enhance or suppress cellular O-GlcNAcylation levels, respectively, in HeLa cells. 25087952 3 2 theme amino 498:502 arg1 carbamate 513:521 O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate 452:521 O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc) 452:530 We used O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc), an inhibitor of O-GlcNAcase, and glucosamine (GlcN), an enhancer of the hexosamine biosynthesis pathway, or O-GlcNAc transferase (OGT) short interfering RNA (siRNA) to enhance or suppress cellular O-GlcNAcylation levels, respectively, in HeLa cells. 25087952 8 3 theme Hsp 1370:1372 arg1 expression 1382:1391 Hsp 70 mRNA expression 1370:1391 Hsp 70 mRNA expression 1370:1391 Finally, Hsp 70 mRNA expression was induced by arsenite, whereas the addition of PUGNAc slightly suppressed its induction. 25087952 4 4 from levels 845:850 arg1 cells 860:864 HeLa cells 855:864 HeLa cells 855:864 The exposure to arsenite increased O-GlcNAcylation and Hsp 70 levels in HeLa cells. 25087952 3 5 theme N-phenyl 504:511 arg1 PUGNAc 524:529 PUGNAc 524:529 PUGNAc 524:529 We used O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc), an inhibitor of O-GlcNAcase, and glucosamine (GlcN), an enhancer of the hexosamine biosynthesis pathway, or O-GlcNAc transferase (OGT) short interfering RNA (siRNA) to enhance or suppress cellular O-GlcNAcylation levels, respectively, in HeLa cells. 25087952 3 5 theme N-phenyl 504:511 arg1 carbamate 513:521 O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate 452:521 O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc) 452:530 We used O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc), an inhibitor of O-GlcNAcase, and glucosamine (GlcN), an enhancer of the hexosamine biosynthesis pathway, or O-GlcNAc transferase (OGT) short interfering RNA (siRNA) to enhance or suppress cellular O-GlcNAcylation levels, respectively, in HeLa cells. 25087952 1 6 theme mitochondrial 252:264 arg1 proteins 283:290 nuclear, mitochondrial, and cytoplasmic proteins 243:290 nuclear, mitochondrial, and cytoplasmic proteins 243:290 O-Linked β-N-acetylglucosamine-modification (O-GlcNAcylation) is a reversible, post-translational, and regulatory modification of nuclear, mitochondrial, and cytoplasmic proteins that is responsive to cellular stress. 25087952 9 7 theme transcriptional 1660:1674 arg1 factors 1676:1682 transcriptional factors 1660:1682 transcriptional factors instead of HSF1 1660:1698 These results indicate that O-GlcNAcylation is related to arsenite-induced Hsp 70 expression, and demonstrated that hyper-O-GlcNAcylation inhibited the induction of Hsp 70 via transcriptional factors instead of HSF1. 25087952 7 8 theme nuclear 1277:1283 arg1 translocation 1285:1297 the nuclear translocation 1273:1297 the nuclear translocation 1273:1297 We then examined the effects of O-GlcNAcylation on the nuclear translocation and phosphorylation of heat shock factor 1 (HSF1), and found that neither the nuclear translocation nor phosphorylation of HSF1 was regulated by O-GlcNAcylation. 25087952 4 9 theme Hsp 838:840 arg1 levels 845:850 O-GlcNAcylation and Hsp 70 levels 818:850 O-GlcNAcylation and Hsp 70 levels in HeLa cells 818:864 The exposure to arsenite increased O-GlcNAcylation and Hsp 70 levels in HeLa cells. 25087952 8 10 theme PUGNAc 1442:1447 arg1 addition 1430:1437 the addition 1426:1437 the addition of PUGNAc 1426:1447 Finally, Hsp 70 mRNA expression was induced by arsenite, whereas the addition of PUGNAc slightly suppressed its induction. 25087952 3 11 theme HeLa 771:774 arg1 cells 776:780 HeLa cells 771:780 HeLa cells 771:780 We used O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc), an inhibitor of O-GlcNAcase, and glucosamine (GlcN), an enhancer of the hexosamine biosynthesis pathway, or O-GlcNAc transferase (OGT) short interfering RNA (siRNA) to enhance or suppress cellular O-GlcNAcylation levels, respectively, in HeLa cells. 25087952 7 12 theme heat 1222:1225 arg1 factor 1233:1238 heat shock factor 1 1222:1240 heat shock factor 1 (HSF1) 1222:1247 We then examined the effects of O-GlcNAcylation on the nuclear translocation and phosphorylation of heat shock factor 1 (HSF1), and found that neither the nuclear translocation nor phosphorylation of HSF1 was regulated by O-GlcNAcylation. 25087952 7 12 theme heat 1222:1225 arg1 HSF1 1243:1246 HSF1 1243:1246 HSF1 1243:1246 We then examined the effects of O-GlcNAcylation on the nuclear translocation and phosphorylation of heat shock factor 1 (HSF1), and found that neither the nuclear translocation nor phosphorylation of HSF1 was regulated by O-GlcNAcylation. 25087952 6 13 theme Hsp 1114:1116 arg1 induction 1101:1109 the induction 1097:1109 the induction of Hsp 70 1097:1119 The pre-treatment with OGT siRNA, which suppressed O-GlcNAcylation levels, did not affect the induction of Hsp 70. 25087952 2 14 theme heat 388:391 arg1 proteins 399:406 heat shock proteins 388:406 heat shock proteins (Hsps) 388:413 However, the role of O-GlcNAcylation in the induction of heat shock proteins (Hsps) by arsenite remains unclear. 25087952 2 14 theme heat 388:391 arg1 Hsps 409:412 Hsps 409:412 Hsps 409:412 However, the role of O-GlcNAcylation in the induction of heat shock proteins (Hsps) by arsenite remains unclear. 25087952 0 15 theme sodium 82:87 arg1 arsenite 89:96 sodium arsenite 82:96 sodium arsenite in HeLa cells 82:110 Hyper-O-GlcNAcylation inhibits the induction of heat shock protein 70 (Hsp 70) by sodium arsenite in HeLa cells. 25087952 3 16 theme short 668:672 arg1 siRNA 691:695 siRNA 691:695 siRNA 691:695 We used O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc), an inhibitor of O-GlcNAcase, and glucosamine (GlcN), an enhancer of the hexosamine biosynthesis pathway, or O-GlcNAc transferase (OGT) short interfering RNA (siRNA) to enhance or suppress cellular O-GlcNAcylation levels, respectively, in HeLa cells. 25087952 3 16 theme short 668:672 arg1 RNA 686:688 short interfering RNA 668:688 short interfering RNA (siRNA) 668:696 We used O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc), an inhibitor of O-GlcNAcase, and glucosamine (GlcN), an enhancer of the hexosamine biosynthesis pathway, or O-GlcNAc transferase (OGT) short interfering RNA (siRNA) to enhance or suppress cellular O-GlcNAcylation levels, respectively, in HeLa cells. 25087952 3 17 theme interfering 674:684 arg1 siRNA 691:695 siRNA 691:695 siRNA 691:695 We used O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc), an inhibitor of O-GlcNAcase, and glucosamine (GlcN), an enhancer of the hexosamine biosynthesis pathway, or O-GlcNAc transferase (OGT) short interfering RNA (siRNA) to enhance or suppress cellular O-GlcNAcylation levels, respectively, in HeLa cells. 25087952 3 17 theme interfering 674:684 arg1 RNA 686:688 short interfering RNA 668:688 short interfering RNA (siRNA) 668:696 We used O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc), an inhibitor of O-GlcNAcase, and glucosamine (GlcN), an enhancer of the hexosamine biosynthesis pathway, or O-GlcNAc transferase (OGT) short interfering RNA (siRNA) to enhance or suppress cellular O-GlcNAcylation levels, respectively, in HeLa cells. 25087952 7 18 theme factor 1233:1238 arg1 translocation 1185:1197 the nuclear translocation 1173:1197 the nuclear translocation 1173:1197 We then examined the effects of O-GlcNAcylation on the nuclear translocation and phosphorylation of heat shock factor 1 (HSF1), and found that neither the nuclear translocation nor phosphorylation of HSF1 was regulated by O-GlcNAcylation. 25087952 7 18 theme factor 1233:1238 arg1 phosphorylation 1203:1217 phosphorylation 1203:1217 phosphorylation of heat shock factor 1 (HSF1) 1203:1247 We then examined the effects of O-GlcNAcylation on the nuclear translocation and phosphorylation of heat shock factor 1 (HSF1), and found that neither the nuclear translocation nor phosphorylation of HSF1 was regulated by O-GlcNAcylation. 25087952 2 19 from role 344:347 arg1 induction 375:383 the induction 371:383 the induction of heat shock proteins (Hsps) by arsenite 371:425 However, the role of O-GlcNAcylation in the induction of heat shock proteins (Hsps) by arsenite remains unclear. 25087952 3 20 theme O-GlcNAcase 549:559 arg1 carbamate 513:521 O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate 452:521 O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc) 452:530 We used O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc), an inhibitor of O-GlcNAcase, and glucosamine (GlcN), an enhancer of the hexosamine biosynthesis pathway, or O-GlcNAc transferase (OGT) short interfering RNA (siRNA) to enhance or suppress cellular O-GlcNAcylation levels, respectively, in HeLa cells. 25087952 3 20 theme O-GlcNAcase 549:559 arg1 inhibitor 536:544 an inhibitor 533:544 an inhibitor of O-GlcNAcase, and glucosamine (GlcN) 533:583 We used O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc), an inhibitor of O-GlcNAcase, and glucosamine (GlcN), an enhancer of the hexosamine biosynthesis pathway, or O-GlcNAc transferase (OGT) short interfering RNA (siRNA) to enhance or suppress cellular O-GlcNAcylation levels, respectively, in HeLa cells. 25087952 3 20 theme O-GlcNAcase 549:559 arg1 transferase 650:660 O-GlcNAc transferase 641:660 O-GlcNAc transferase (OGT) 641:666 We used O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc), an inhibitor of O-GlcNAcase, and glucosamine (GlcN), an enhancer of the hexosamine biosynthesis pathway, or O-GlcNAc transferase (OGT) short interfering RNA (siRNA) to enhance or suppress cellular O-GlcNAcylation levels, respectively, in HeLa cells. 25087952 3 20 theme O-GlcNAcase 549:559 arg1 OGT 663:665 OGT 663:665 OGT 663:665 We used O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc), an inhibitor of O-GlcNAcase, and glucosamine (GlcN), an enhancer of the hexosamine biosynthesis pathway, or O-GlcNAc transferase (OGT) short interfering RNA (siRNA) to enhance or suppress cellular O-GlcNAcylation levels, respectively, in HeLa cells. 25087952 3 20 theme O-GlcNAcase 549:559 arg1 PUGNAc 524:529 PUGNAc 524:529 PUGNAc 524:529 We used O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc), an inhibitor of O-GlcNAcase, and glucosamine (GlcN), an enhancer of the hexosamine biosynthesis pathway, or O-GlcNAc transferase (OGT) short interfering RNA (siRNA) to enhance or suppress cellular O-GlcNAcylation levels, respectively, in HeLa cells. 25087952 3 20 theme O-GlcNAcase 549:559 arg1 enhancer 589:596 an enhancer 586:596 an enhancer of the hexosamine biosynthesis pathway 586:635 We used O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc), an inhibitor of O-GlcNAcase, and glucosamine (GlcN), an enhancer of the hexosamine biosynthesis pathway, or O-GlcNAc transferase (OGT) short interfering RNA (siRNA) to enhance or suppress cellular O-GlcNAcylation levels, respectively, in HeLa cells. 25087952 1 21 theme cytoplasmic 271:281 arg1 proteins 283:290 nuclear, mitochondrial, and cytoplasmic proteins 243:290 nuclear, mitochondrial, and cytoplasmic proteins 243:290 O-Linked β-N-acetylglucosamine-modification (O-GlcNAcylation) is a reversible, post-translational, and regulatory modification of nuclear, mitochondrial, and cytoplasmic proteins that is responsive to cellular stress. 25087952 7 22 from effects 1143:1149 arg1 translocation 1185:1197 the nuclear translocation 1173:1197 the nuclear translocation 1173:1197 We then examined the effects of O-GlcNAcylation on the nuclear translocation and phosphorylation of heat shock factor 1 (HSF1), and found that neither the nuclear translocation nor phosphorylation of HSF1 was regulated by O-GlcNAcylation. 25087952 7 22 from effects 1143:1149 arg1 phosphorylation 1203:1217 phosphorylation 1203:1217 phosphorylation of heat shock factor 1 (HSF1) 1203:1247 We then examined the effects of O-GlcNAcylation on the nuclear translocation and phosphorylation of heat shock factor 1 (HSF1), and found that neither the nuclear translocation nor phosphorylation of HSF1 was regulated by O-GlcNAcylation. 25087952 1 23 theme reversible 180:189 arg1 β-N-acetylglucosamine-modification 122:155 O-Linked β-N-acetylglucosamine-modification 113:155 O-Linked β-N-acetylglucosamine-modification (O-GlcNAcylation) 113:173 O-Linked β-N-acetylglucosamine-modification (O-GlcNAcylation) is a reversible, post-translational, and regulatory modification of nuclear, mitochondrial, and cytoplasmic proteins that is responsive to cellular stress. 25087952 1 23 theme reversible 180:189 arg1 modification 227:238 a reversible, post-translational, and regulatory modification 178:238 a reversible, post-translational, and regulatory modification of nuclear, mitochondrial, and cytoplasmic proteins that is responsive to cellular stress 178:328 O-Linked β-N-acetylglucosamine-modification (O-GlcNAcylation) is a reversible, post-translational, and regulatory modification of nuclear, mitochondrial, and cytoplasmic proteins that is responsive to cellular stress. 25087952 1 23 theme reversible 180:189 arg1 responsive 300:309 responsive 300:309 responsive 300:309 O-Linked β-N-acetylglucosamine-modification (O-GlcNAcylation) is a reversible, post-translational, and regulatory modification of nuclear, mitochondrial, and cytoplasmic proteins that is responsive to cellular stress. 25087952 6 24 with pre-treatment 1011:1023 arg1 siRNA 1034:1038 OGT siRNA 1030:1038 OGT siRNA 1030:1038 The pre-treatment with OGT siRNA, which suppressed O-GlcNAcylation levels, did not affect the induction of Hsp 70. 25087952 1 25 theme proteins 283:290 arg1 β-N-acetylglucosamine-modification 122:155 O-Linked β-N-acetylglucosamine-modification 113:155 O-Linked β-N-acetylglucosamine-modification (O-GlcNAcylation) 113:173 O-Linked β-N-acetylglucosamine-modification (O-GlcNAcylation) is a reversible, post-translational, and regulatory modification of nuclear, mitochondrial, and cytoplasmic proteins that is responsive to cellular stress. 25087952 1 25 theme proteins 283:290 arg1 modification 227:238 a reversible, post-translational, and regulatory modification 178:238 a reversible, post-translational, and regulatory modification of nuclear, mitochondrial, and cytoplasmic proteins that is responsive to cellular stress 178:328 O-Linked β-N-acetylglucosamine-modification (O-GlcNAcylation) is a reversible, post-translational, and regulatory modification of nuclear, mitochondrial, and cytoplasmic proteins that is responsive to cellular stress. 25087952 1 25 theme proteins 283:290 arg1 responsive 300:309 responsive 300:309 responsive 300:309 O-Linked β-N-acetylglucosamine-modification (O-GlcNAcylation) is a reversible, post-translational, and regulatory modification of nuclear, mitochondrial, and cytoplasmic proteins that is responsive to cellular stress. 25087952 0 26 theme HeLa 101:104 arg1 cells 106:110 HeLa cells 101:110 HeLa cells 101:110 Hyper-O-GlcNAcylation inhibits the induction of heat shock protein 70 (Hsp 70) by sodium arsenite in HeLa cells. 25087952 9 27 theme arsenite-induced 1542:1557 arg1 expression 1566:1575 arsenite-induced Hsp 70 expression 1542:1575 arsenite-induced Hsp 70 expression 1542:1575 These results indicate that O-GlcNAcylation is related to arsenite-induced Hsp 70 expression, and demonstrated that hyper-O-GlcNAcylation inhibited the induction of Hsp 70 via transcriptional factors instead of HSF1. 25087952 3 28 used used 447:450 arg2 We 444:445 We 444:445 We 444:445 We used O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc), an inhibitor of O-GlcNAcase, and glucosamine (GlcN), an enhancer of the hexosamine biosynthesis pathway, or O-GlcNAc transferase (OGT) short interfering RNA (siRNA) to enhance or suppress cellular O-GlcNAcylation levels, respectively, in HeLa cells. 25087952 5 29 with pre-treatment 880:892 arg1 GlcN 909:912 GlcN 909:912 GlcN 909:912 However, the pre-treatment with PUGNAc or GlcN, which enhanced O-GlcNAcylation levels, decreased the arsenite-induced expression of Hsp 70. 25087952 5 29 with pre-treatment 880:892 arg1 PUGNAc 899:904 PUGNAc 899:904 PUGNAc 899:904 However, the pre-treatment with PUGNAc or GlcN, which enhanced O-GlcNAcylation levels, decreased the arsenite-induced expression of Hsp 70. 25087952 3 30 theme hexosamine 605:614 arg1 pathway 629:635 the hexosamine biosynthesis pathway 601:635 the hexosamine biosynthesis pathway 601:635 We used O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc), an inhibitor of O-GlcNAcase, and glucosamine (GlcN), an enhancer of the hexosamine biosynthesis pathway, or O-GlcNAc transferase (OGT) short interfering RNA (siRNA) to enhance or suppress cellular O-GlcNAcylation levels, respectively, in HeLa cells. 25087952 7 31 theme nuclear 1177:1183 arg1 translocation 1185:1197 the nuclear translocation 1173:1197 the nuclear translocation 1173:1197 We then examined the effects of O-GlcNAcylation on the nuclear translocation and phosphorylation of heat shock factor 1 (HSF1), and found that neither the nuclear translocation nor phosphorylation of HSF1 was regulated by O-GlcNAcylation. 25087952 1 32 theme post-translational 192:209 arg1 β-N-acetylglucosamine-modification 122:155 O-Linked β-N-acetylglucosamine-modification 113:155 O-Linked β-N-acetylglucosamine-modification (O-GlcNAcylation) 113:173 O-Linked β-N-acetylglucosamine-modification (O-GlcNAcylation) is a reversible, post-translational, and regulatory modification of nuclear, mitochondrial, and cytoplasmic proteins that is responsive to cellular stress. 25087952 1 32 theme post-translational 192:209 arg1 modification 227:238 a reversible, post-translational, and regulatory modification 178:238 a reversible, post-translational, and regulatory modification of nuclear, mitochondrial, and cytoplasmic proteins that is responsive to cellular stress 178:328 O-Linked β-N-acetylglucosamine-modification (O-GlcNAcylation) is a reversible, post-translational, and regulatory modification of nuclear, mitochondrial, and cytoplasmic proteins that is responsive to cellular stress. 25087952 1 32 theme post-translational 192:209 arg1 responsive 300:309 responsive 300:309 responsive 300:309 O-Linked β-N-acetylglucosamine-modification (O-GlcNAcylation) is a reversible, post-translational, and regulatory modification of nuclear, mitochondrial, and cytoplasmic proteins that is responsive to cellular stress. 25087952 0 33 theme heat 48:51 arg1 Hsp 71:73 Hsp 70 71:76 Hsp 70 71:76 Hyper-O-GlcNAcylation inhibits the induction of heat shock protein 70 (Hsp 70) by sodium arsenite in HeLa cells. 25087952 0 33 theme heat 48:51 arg1 protein 59:65 heat shock protein 70 48:68 heat shock protein 70 (Hsp 70) 48:77 Hyper-O-GlcNAcylation inhibits the induction of heat shock protein 70 (Hsp 70) by sodium arsenite in HeLa cells. 25087952 3 34 theme biosynthesis 616:627 arg1 pathway 629:635 the hexosamine biosynthesis pathway 601:635 the hexosamine biosynthesis pathway 601:635 We used O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc), an inhibitor of O-GlcNAcase, and glucosamine (GlcN), an enhancer of the hexosamine biosynthesis pathway, or O-GlcNAc transferase (OGT) short interfering RNA (siRNA) to enhance or suppress cellular O-GlcNAcylation levels, respectively, in HeLa cells. 25087952 2 35 theme proteins 399:406 arg1 induction 375:383 the induction 371:383 the induction of heat shock proteins (Hsps) by arsenite 371:425 However, the role of O-GlcNAcylation in the induction of heat shock proteins (Hsps) by arsenite remains unclear. 25087952 6 36 theme OGT 1030:1032 arg1 siRNA 1034:1038 OGT siRNA 1030:1038 OGT siRNA 1030:1038 The pre-treatment with OGT siRNA, which suppressed O-GlcNAcylation levels, did not affect the induction of Hsp 70. 25087952 3 37 theme cellular 721:728 arg1 levels 746:751 cellular O-GlcNAcylation levels 721:751 cellular O-GlcNAcylation levels 721:751 We used O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc), an inhibitor of O-GlcNAcase, and glucosamine (GlcN), an enhancer of the hexosamine biosynthesis pathway, or O-GlcNAc transferase (OGT) short interfering RNA (siRNA) to enhance or suppress cellular O-GlcNAcylation levels, respectively, in HeLa cells. 25087952 7 38 theme HSF1 1322:1325 arg1 phosphorylation 1303:1317 phosphorylation 1303:1317 phosphorylation of HSF1 1303:1325 We then examined the effects of O-GlcNAcylation on the nuclear translocation and phosphorylation of heat shock factor 1 (HSF1), and found that neither the nuclear translocation nor phosphorylation of HSF1 was regulated by O-GlcNAcylation. 25087952 2 39 theme shock 393:397 arg1 proteins 399:406 heat shock proteins 388:406 heat shock proteins (Hsps) 388:413 However, the role of O-GlcNAcylation in the induction of heat shock proteins (Hsps) by arsenite remains unclear. 25087952 2 39 theme shock 393:397 arg1 Hsps 409:412 Hsps 409:412 Hsps 409:412 However, the role of O-GlcNAcylation in the induction of heat shock proteins (Hsps) by arsenite remains unclear. 25087952 0 40 theme protein 59:65 arg1 induction 35:43 the induction 31:43 the induction of heat shock protein 70 (Hsp 70) by sodium arsenite in HeLa cells 31:110 Hyper-O-GlcNAcylation inhibits the induction of heat shock protein 70 (Hsp 70) by sodium arsenite in HeLa cells. 25087952 3 41 theme O-GlcNAcylation 730:744 arg1 levels 746:751 cellular O-GlcNAcylation levels 721:751 cellular O-GlcNAcylation levels 721:751 We used O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc), an inhibitor of O-GlcNAcase, and glucosamine (GlcN), an enhancer of the hexosamine biosynthesis pathway, or O-GlcNAc transferase (OGT) short interfering RNA (siRNA) to enhance or suppress cellular O-GlcNAcylation levels, respectively, in HeLa cells. 25087952 3 42 from levels 746:751 arg1 cells 776:780 HeLa cells 771:780 HeLa cells 771:780 We used O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc), an inhibitor of O-GlcNAcase, and glucosamine (GlcN), an enhancer of the hexosamine biosynthesis pathway, or O-GlcNAc transferase (OGT) short interfering RNA (siRNA) to enhance or suppress cellular O-GlcNAcylation levels, respectively, in HeLa cells. 25087952 5 43 theme Hsp 999:1001 arg1 expression 985:994 the arsenite-induced expression 964:994 the arsenite-induced expression of Hsp 70 964:1004 However, the pre-treatment with PUGNAc or GlcN, which enhanced O-GlcNAcylation levels, decreased the arsenite-induced expression of Hsp 70. 25087952 5 44 theme arsenite-induced 968:983 arg1 expression 985:994 the arsenite-induced expression 964:994 the arsenite-induced expression of Hsp 70 964:1004 However, the pre-treatment with PUGNAc or GlcN, which enhanced O-GlcNAcylation levels, decreased the arsenite-induced expression of Hsp 70. 25087952 3 45 theme 2-acetamido-2-deoxy-D-glucopyranosylidene 455:495 arg1 PUGNAc 524:529 PUGNAc 524:529 PUGNAc 524:529 We used O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc), an inhibitor of O-GlcNAcase, and glucosamine (GlcN), an enhancer of the hexosamine biosynthesis pathway, or O-GlcNAc transferase (OGT) short interfering RNA (siRNA) to enhance or suppress cellular O-GlcNAcylation levels, respectively, in HeLa cells. 25087952 3 45 theme 2-acetamido-2-deoxy-D-glucopyranosylidene 455:495 arg1 carbamate 513:521 O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate 452:521 O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc) 452:530 We used O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc), an inhibitor of O-GlcNAcase, and glucosamine (GlcN), an enhancer of the hexosamine biosynthesis pathway, or O-GlcNAc transferase (OGT) short interfering RNA (siRNA) to enhance or suppress cellular O-GlcNAcylation levels, respectively, in HeLa cells. 25087952 0 46 theme shock 53:57 arg1 Hsp 71:73 Hsp 70 71:76 Hsp 70 71:76 Hyper-O-GlcNAcylation inhibits the induction of heat shock protein 70 (Hsp 70) by sodium arsenite in HeLa cells. 25087952 0 46 theme shock 53:57 arg1 protein 59:65 heat shock protein 70 48:68 heat shock protein 70 (Hsp 70) 48:77 Hyper-O-GlcNAcylation inhibits the induction of heat shock protein 70 (Hsp 70) by sodium arsenite in HeLa cells. 25087952 1 47 theme cellular 314:321 arg1 stress 323:328 cellular stress 314:328 cellular stress 314:328 O-Linked β-N-acetylglucosamine-modification (O-GlcNAcylation) is a reversible, post-translational, and regulatory modification of nuclear, mitochondrial, and cytoplasmic proteins that is responsive to cellular stress. 25087952 9 48 theme Hsp 1649:1651 arg1 induction 1636:1644 the induction 1632:1644 the induction of Hsp 70 1632:1654 These results indicate that O-GlcNAcylation is related to arsenite-induced Hsp 70 expression, and demonstrated that hyper-O-GlcNAcylation inhibited the induction of Hsp 70 via transcriptional factors instead of HSF1. 25087952 0 49 from arsenite 89:96 arg1 cells 106:110 HeLa cells 101:110 HeLa cells 101:110 Hyper-O-GlcNAcylation inhibits the induction of heat shock protein 70 (Hsp 70) by sodium arsenite in HeLa cells. 25087952 3 50 theme glucosamine 566:576 arg1 carbamate 513:521 O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate 452:521 O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc) 452:530 We used O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc), an inhibitor of O-GlcNAcase, and glucosamine (GlcN), an enhancer of the hexosamine biosynthesis pathway, or O-GlcNAc transferase (OGT) short interfering RNA (siRNA) to enhance or suppress cellular O-GlcNAcylation levels, respectively, in HeLa cells. 25087952 3 50 theme glucosamine 566:576 arg1 inhibitor 536:544 an inhibitor 533:544 an inhibitor of O-GlcNAcase, and glucosamine (GlcN) 533:583 We used O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc), an inhibitor of O-GlcNAcase, and glucosamine (GlcN), an enhancer of the hexosamine biosynthesis pathway, or O-GlcNAc transferase (OGT) short interfering RNA (siRNA) to enhance or suppress cellular O-GlcNAcylation levels, respectively, in HeLa cells. 25087952 3 50 theme glucosamine 566:576 arg1 transferase 650:660 O-GlcNAc transferase 641:660 O-GlcNAc transferase (OGT) 641:666 We used O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc), an inhibitor of O-GlcNAcase, and glucosamine (GlcN), an enhancer of the hexosamine biosynthesis pathway, or O-GlcNAc transferase (OGT) short interfering RNA (siRNA) to enhance or suppress cellular O-GlcNAcylation levels, respectively, in HeLa cells. 25087952 3 50 theme glucosamine 566:576 arg1 OGT 663:665 OGT 663:665 OGT 663:665 We used O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc), an inhibitor of O-GlcNAcase, and glucosamine (GlcN), an enhancer of the hexosamine biosynthesis pathway, or O-GlcNAc transferase (OGT) short interfering RNA (siRNA) to enhance or suppress cellular O-GlcNAcylation levels, respectively, in HeLa cells. 25087952 3 50 theme glucosamine 566:576 arg1 PUGNAc 524:529 PUGNAc 524:529 PUGNAc 524:529 We used O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc), an inhibitor of O-GlcNAcase, and glucosamine (GlcN), an enhancer of the hexosamine biosynthesis pathway, or O-GlcNAc transferase (OGT) short interfering RNA (siRNA) to enhance or suppress cellular O-GlcNAcylation levels, respectively, in HeLa cells. 25087952 3 50 theme glucosamine 566:576 arg1 enhancer 589:596 an enhancer 586:596 an enhancer of the hexosamine biosynthesis pathway 586:635 We used O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc), an inhibitor of O-GlcNAcase, and glucosamine (GlcN), an enhancer of the hexosamine biosynthesis pathway, or O-GlcNAc transferase (OGT) short interfering RNA (siRNA) to enhance or suppress cellular O-GlcNAcylation levels, respectively, in HeLa cells. 25087952 7 51 theme shock 1227:1231 arg1 factor 1233:1238 heat shock factor 1 1222:1240 heat shock factor 1 (HSF1) 1222:1247 We then examined the effects of O-GlcNAcylation on the nuclear translocation and phosphorylation of heat shock factor 1 (HSF1), and found that neither the nuclear translocation nor phosphorylation of HSF1 was regulated by O-GlcNAcylation. 25087952 7 51 theme shock 1227:1231 arg1 HSF1 1243:1246 HSF1 1243:1246 HSF1 1243:1246 We then examined the effects of O-GlcNAcylation on the nuclear translocation and phosphorylation of heat shock factor 1 (HSF1), and found that neither the nuclear translocation nor phosphorylation of HSF1 was regulated by O-GlcNAcylation. 25087952 4 52 theme HeLa 855:858 arg1 cells 860:864 HeLa cells 855:864 HeLa cells 855:864 The exposure to arsenite increased O-GlcNAcylation and Hsp 70 levels in HeLa cells. 25087952 3 53 theme O-GlcNAc 641:648 arg1 OGT 663:665 OGT 663:665 OGT 663:665 We used O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc), an inhibitor of O-GlcNAcase, and glucosamine (GlcN), an enhancer of the hexosamine biosynthesis pathway, or O-GlcNAc transferase (OGT) short interfering RNA (siRNA) to enhance or suppress cellular O-GlcNAcylation levels, respectively, in HeLa cells. 25087952 3 53 theme O-GlcNAc 641:648 arg1 transferase 650:660 O-GlcNAc transferase 641:660 O-GlcNAc transferase (OGT) 641:666 We used O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc), an inhibitor of O-GlcNAcase, and glucosamine (GlcN), an enhancer of the hexosamine biosynthesis pathway, or O-GlcNAc transferase (OGT) short interfering RNA (siRNA) to enhance or suppress cellular O-GlcNAcylation levels, respectively, in HeLa cells. 25087952 9 54 theme Hsp 1559:1561 arg1 expression 1566:1575 arsenite-induced Hsp 70 expression 1542:1575 arsenite-induced Hsp 70 expression 1542:1575 These results indicate that O-GlcNAcylation is related to arsenite-induced Hsp 70 expression, and demonstrated that hyper-O-GlcNAcylation inhibited the induction of Hsp 70 via transcriptional factors instead of HSF1. 25087952 3 55 theme O- 452:453 arg1 PUGNAc 524:529 PUGNAc 524:529 PUGNAc 524:529 We used O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc), an inhibitor of O-GlcNAcase, and glucosamine (GlcN), an enhancer of the hexosamine biosynthesis pathway, or O-GlcNAc transferase (OGT) short interfering RNA (siRNA) to enhance or suppress cellular O-GlcNAcylation levels, respectively, in HeLa cells. 25087952 3 55 theme O- 452:453 arg1 carbamate 513:521 O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate 452:521 O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc) 452:530 We used O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc), an inhibitor of O-GlcNAcase, and glucosamine (GlcN), an enhancer of the hexosamine biosynthesis pathway, or O-GlcNAc transferase (OGT) short interfering RNA (siRNA) to enhance or suppress cellular O-GlcNAcylation levels, respectively, in HeLa cells. 25087952 3 56 dep carbamate 513:521 arg1 siRNA 691:695 siRNA 691:695 siRNA 691:695 We used O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc), an inhibitor of O-GlcNAcase, and glucosamine (GlcN), an enhancer of the hexosamine biosynthesis pathway, or O-GlcNAc transferase (OGT) short interfering RNA (siRNA) to enhance or suppress cellular O-GlcNAcylation levels, respectively, in HeLa cells. 25087952 3 56 dep carbamate 513:521 arg1 RNA 686:688 short interfering RNA 668:688 short interfering RNA (siRNA) 668:696 We used O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc), an inhibitor of O-GlcNAcase, and glucosamine (GlcN), an enhancer of the hexosamine biosynthesis pathway, or O-GlcNAc transferase (OGT) short interfering RNA (siRNA) to enhance or suppress cellular O-GlcNAcylation levels, respectively, in HeLa cells. 25087952 1 57 theme regulatory 216:225 arg1 β-N-acetylglucosamine-modification 122:155 O-Linked β-N-acetylglucosamine-modification 113:155 O-Linked β-N-acetylglucosamine-modification (O-GlcNAcylation) 113:173 O-Linked β-N-acetylglucosamine-modification (O-GlcNAcylation) is a reversible, post-translational, and regulatory modification of nuclear, mitochondrial, and cytoplasmic proteins that is responsive to cellular stress. 25087952 1 57 theme regulatory 216:225 arg1 modification 227:238 a reversible, post-translational, and regulatory modification 178:238 a reversible, post-translational, and regulatory modification of nuclear, mitochondrial, and cytoplasmic proteins that is responsive to cellular stress 178:328 O-Linked β-N-acetylglucosamine-modification (O-GlcNAcylation) is a reversible, post-translational, and regulatory modification of nuclear, mitochondrial, and cytoplasmic proteins that is responsive to cellular stress. 25087952 1 57 theme regulatory 216:225 arg1 responsive 300:309 responsive 300:309 responsive 300:309 O-Linked β-N-acetylglucosamine-modification (O-GlcNAcylation) is a reversible, post-translational, and regulatory modification of nuclear, mitochondrial, and cytoplasmic proteins that is responsive to cellular stress. 25087952 9 58 theme HSF1 1695:1698 arg1 factors 1676:1682 transcriptional factors 1660:1682 transcriptional factors instead of HSF1 1660:1698 These results indicate that O-GlcNAcylation is related to arsenite-induced Hsp 70 expression, and demonstrated that hyper-O-GlcNAcylation inhibited the induction of Hsp 70 via transcriptional factors instead of HSF1. 25087952 3 59 theme pathway 629:635 arg1 carbamate 513:521 O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate 452:521 O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc) 452:530 We used O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc), an inhibitor of O-GlcNAcase, and glucosamine (GlcN), an enhancer of the hexosamine biosynthesis pathway, or O-GlcNAc transferase (OGT) short interfering RNA (siRNA) to enhance or suppress cellular O-GlcNAcylation levels, respectively, in HeLa cells. 25087952 3 59 theme pathway 629:635 arg1 inhibitor 536:544 an inhibitor 533:544 an inhibitor of O-GlcNAcase, and glucosamine (GlcN) 533:583 We used O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc), an inhibitor of O-GlcNAcase, and glucosamine (GlcN), an enhancer of the hexosamine biosynthesis pathway, or O-GlcNAc transferase (OGT) short interfering RNA (siRNA) to enhance or suppress cellular O-GlcNAcylation levels, respectively, in HeLa cells. 25087952 3 59 theme pathway 629:635 arg1 transferase 650:660 O-GlcNAc transferase 641:660 O-GlcNAc transferase (OGT) 641:666 We used O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc), an inhibitor of O-GlcNAcase, and glucosamine (GlcN), an enhancer of the hexosamine biosynthesis pathway, or O-GlcNAc transferase (OGT) short interfering RNA (siRNA) to enhance or suppress cellular O-GlcNAcylation levels, respectively, in HeLa cells. 25087952 3 59 theme pathway 629:635 arg1 OGT 663:665 OGT 663:665 OGT 663:665 We used O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc), an inhibitor of O-GlcNAcase, and glucosamine (GlcN), an enhancer of the hexosamine biosynthesis pathway, or O-GlcNAc transferase (OGT) short interfering RNA (siRNA) to enhance or suppress cellular O-GlcNAcylation levels, respectively, in HeLa cells. 25087952 3 59 theme pathway 629:635 arg1 PUGNAc 524:529 PUGNAc 524:529 PUGNAc 524:529 We used O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc), an inhibitor of O-GlcNAcase, and glucosamine (GlcN), an enhancer of the hexosamine biosynthesis pathway, or O-GlcNAc transferase (OGT) short interfering RNA (siRNA) to enhance or suppress cellular O-GlcNAcylation levels, respectively, in HeLa cells. 25087952 3 59 theme pathway 629:635 arg1 enhancer 589:596 an enhancer 586:596 an enhancer of the hexosamine biosynthesis pathway 586:635 We used O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc), an inhibitor of O-GlcNAcase, and glucosamine (GlcN), an enhancer of the hexosamine biosynthesis pathway, or O-GlcNAc transferase (OGT) short interfering RNA (siRNA) to enhance or suppress cellular O-GlcNAcylation levels, respectively, in HeLa cells. 25087952 5 60 theme O-GlcNAcylation 930:944 arg1 levels 946:951 O-GlcNAcylation levels 930:951 O-GlcNAcylation levels 930:951 However, the pre-treatment with PUGNAc or GlcN, which enhanced O-GlcNAcylation levels, decreased the arsenite-induced expression of Hsp 70. 25087952 6 61 theme O-GlcNAcylation 1058:1072 arg1 levels 1074:1079 O-GlcNAcylation levels 1058:1079 O-GlcNAcylation levels 1058:1079 The pre-treatment with OGT siRNA, which suppressed O-GlcNAcylation levels, did not affect the induction of Hsp 70. 25087952 7 62 theme O-GlcNAcylation 1154:1168 arg1 effects 1143:1149 the effects 1139:1149 the effects of O-GlcNAcylation on the nuclear translocation and phosphorylation of heat shock factor 1 (HSF1) 1139:1247 We then examined the effects of O-GlcNAcylation on the nuclear translocation and phosphorylation of heat shock factor 1 (HSF1), and found that neither the nuclear translocation nor phosphorylation of HSF1 was regulated by O-GlcNAcylation. 25087952 1 63 theme O-Linked 113:120 arg1 β-N-acetylglucosamine-modification 122:155 O-Linked β-N-acetylglucosamine-modification 113:155 O-Linked β-N-acetylglucosamine-modification (O-GlcNAcylation) 113:173 O-Linked β-N-acetylglucosamine-modification (O-GlcNAcylation) is a reversible, post-translational, and regulatory modification of nuclear, mitochondrial, and cytoplasmic proteins that is responsive to cellular stress. 25087952 1 63 theme O-Linked 113:120 arg1 modification 227:238 a reversible, post-translational, and regulatory modification 178:238 a reversible, post-translational, and regulatory modification of nuclear, mitochondrial, and cytoplasmic proteins that is responsive to cellular stress 178:328 O-Linked β-N-acetylglucosamine-modification (O-GlcNAcylation) is a reversible, post-translational, and regulatory modification of nuclear, mitochondrial, and cytoplasmic proteins that is responsive to cellular stress. 25087952 1 63 theme O-Linked 113:120 arg1 responsive 300:309 responsive 300:309 responsive 300:309 O-Linked β-N-acetylglucosamine-modification (O-GlcNAcylation) is a reversible, post-translational, and regulatory modification of nuclear, mitochondrial, and cytoplasmic proteins that is responsive to cellular stress. 25087952 1 63 theme O-Linked 113:120 arg1 O-GlcNAcylation 158:172 O-GlcNAcylation 158:172 O-GlcNAcylation 158:172 O-Linked β-N-acetylglucosamine-modification (O-GlcNAcylation) is a reversible, post-translational, and regulatory modification of nuclear, mitochondrial, and cytoplasmic proteins that is responsive to cellular stress. 25087952 2 64 theme O-GlcNAcylation 352:366 arg1 role 344:347 the role 340:347 the role of O-GlcNAcylation in the induction of heat shock proteins (Hsps) by arsenite 340:425 However, the role of O-GlcNAcylation in the induction of heat shock proteins (Hsps) by arsenite remains unclear. 25087952 1 65 theme nuclear 243:249 arg1 proteins 283:290 nuclear, mitochondrial, and cytoplasmic proteins 243:290 nuclear, mitochondrial, and cytoplasmic proteins 243:290 O-Linked β-N-acetylglucosamine-modification (O-GlcNAcylation) is a reversible, post-translational, and regulatory modification of nuclear, mitochondrial, and cytoplasmic proteins that is responsive to cellular stress. 24890740 0 0 theme tripartite 89:98 arg1 vaccines 100:107 fully synthetic aberrantly glycosylated MUC1 tripartite vaccines 44:107 fully synthetic aberrantly glycosylated MUC1 tripartite vaccines 44:107 Immune and anticancer responses elicited by fully synthetic aberrantly glycosylated MUC1 tripartite vaccines modified by a TLR2 or TLR9 agonist. 24890740 4 1 theme CysSK4 852:857 arg1 compound 871:878 the Pam3 CysSK4 -containing compound 843:878 the Pam3 CysSK4 -containing compound 843:878 It was found that the Pam3 CysSK4 -containing compound elicits more potent antigenic and cellular immune responses, resulting in a therapeutic effect in a mouse model of mammary cancer. 24890740 5 2 theme vaccine 1104:1110 arg1 adjuvant 1079:1086 adjuvant 1079:1086 adjuvant 1079:1086 It is thus shown, for the first time, that the nature of an inbuilt adjuvant of a tripartite vaccine can significantly impact the quality of immune responses elicited against a tumor-associated glycopeptide. 24890740 1 3 theme mucin 149:153 arg1 MUC1 155:158 The mucin MUC1 145:158 The mucin MUC1 145:158 The mucin MUC1 is overexpressed and aberrantly glycosylated by many epithelial cancer cells manifested by truncated O-linked saccharides. 24890740 1 4 theme truncated 251:259 arg1 saccharides 270:280 truncated O-linked saccharides 251:280 truncated O-linked saccharides 251:280 The mucin MUC1 is overexpressed and aberrantly glycosylated by many epithelial cancer cells manifested by truncated O-linked saccharides. 24890740 0 5 theme MUC1 84:87 arg1 vaccines 100:107 fully synthetic aberrantly glycosylated MUC1 tripartite vaccines 44:107 fully synthetic aberrantly glycosylated MUC1 tripartite vaccines 44:107 Immune and anticancer responses elicited by fully synthetic aberrantly glycosylated MUC1 tripartite vaccines modified by a TLR2 or TLR9 agonist. 24890740 5 6 theme adjuvant 1079:1086 arg1 nature 1058:1063 the nature 1054:1063 the nature of an inbuilt adjuvant of a tripartite vaccine 1054:1110 It is thus shown, for the first time, that the nature of an inbuilt adjuvant of a tripartite vaccine can significantly impact the quality of immune responses elicited against a tumor-associated glycopeptide. 24890740 4 7 theme Pam3 847:850 arg1 compound 871:878 the Pam3 CysSK4 -containing compound 843:878 the Pam3 CysSK4 -containing compound 843:878 It was found that the Pam3 CysSK4 -containing compound elicits more potent antigenic and cellular immune responses, resulting in a therapeutic effect in a mouse model of mammary cancer. 24890740 1 8 theme O-linked 261:268 arg1 saccharides 270:280 truncated O-linked saccharides 251:280 truncated O-linked saccharides 251:280 The mucin MUC1 is overexpressed and aberrantly glycosylated by many epithelial cancer cells manifested by truncated O-linked saccharides. 24890740 6 9 theme CTLs 1378:1381 arg1 cytotoxicity 1347:1358 the cytotoxicity 1343:1358 the cytotoxicity of tumor-specific CTLs 1343:1381 The unique adjuvant properties of Pam3 CysSK4 , which can reduce the suppressive function of regulatory T cells and enhance the cytotoxicity of tumor-specific CTLs, are likely responsible for the superior properties of the vaccine candidate 1. 24890740 6 10 theme superior 1415:1422 arg1 properties 1424:1433 the superior properties 1411:1433 the superior properties of the vaccine candidate 1 1411:1460 The unique adjuvant properties of Pam3 CysSK4 , which can reduce the suppressive function of regulatory T cells and enhance the cytotoxicity of tumor-specific CTLs, are likely responsible for the superior properties of the vaccine candidate 1. 24890740 5 11 theme responses 1159:1167 arg1 quality 1141:1147 the quality 1137:1147 the quality of immune responses elicited against a tumor-associated glycopeptide 1137:1216 It is thus shown, for the first time, that the nature of an inbuilt adjuvant of a tripartite vaccine can significantly impact the quality of immune responses elicited against a tumor-associated glycopeptide. 24890740 2 12 theme specific 558:565 arg1 antibodies 547:556 ADCC-mediating antibodies 532:556 ADCC-mediating antibodies specific for the tumor form of MUC1 532:592 Although tumor-associated MUC1 has generated considerable attention because of its potential for the development of a therapeutic cancer vaccine, it has been difficult to design constructs that consistently induce cytotoxic T-lymphocytes (CTLs) and ADCC-mediating antibodies specific for the tumor form of MUC1. 24890740 4 13 theme -containing 859:869 arg1 compound 871:878 the Pam3 CysSK4 -containing compound 843:878 the Pam3 CysSK4 -containing compound 843:878 It was found that the Pam3 CysSK4 -containing compound elicits more potent antigenic and cellular immune responses, resulting in a therapeutic effect in a mouse model of mammary cancer. 24890740 5 14 gly glycopeptide 1205:1216 arg2 glycopeptide 1205:1216 a tumor-associated glycopeptide 1186:1216 a tumor-associated glycopeptide 1186:1216 It is thus shown, for the first time, that the nature of an inbuilt adjuvant of a tripartite vaccine can significantly impact the quality of immune responses elicited against a tumor-associated glycopeptide. 24890740 0 15 gly glycosylated 71:82 arg1 vaccines 100:107 fully synthetic aberrantly glycosylated MUC1 tripartite vaccines 44:107 fully synthetic aberrantly glycosylated MUC1 tripartite vaccines 44:107 Immune and anticancer responses elicited by fully synthetic aberrantly glycosylated MUC1 tripartite vaccines modified by a TLR2 or TLR9 agonist. 24890740 4 16 theme mouse 980:984 arg1 model 986:990 a mouse model 978:990 a mouse model of mammary cancer 978:1008 It was found that the Pam3 CysSK4 -containing compound elicits more potent antigenic and cellular immune responses, resulting in a therapeutic effect in a mouse model of mammary cancer. 24890740 6 17 theme T 1323:1323 arg1 cells 1325:1329 regulatory T cells 1312:1329 regulatory T cells 1312:1329 The unique adjuvant properties of Pam3 CysSK4 , which can reduce the suppressive function of regulatory T cells and enhance the cytotoxicity of tumor-specific CTLs, are likely responsible for the superior properties of the vaccine candidate 1. 24890740 6 18 theme adjuvant 1230:1237 arg1 responsible 1395:1405 responsible 1395:1405 responsible 1395:1405 The unique adjuvant properties of Pam3 CysSK4 , which can reduce the suppressive function of regulatory T cells and enhance the cytotoxicity of tumor-specific CTLs, are likely responsible for the superior properties of the vaccine candidate 1. 24890740 6 18 theme adjuvant 1230:1237 arg1 properties 1239:1248 The unique adjuvant properties 1219:1248 The unique adjuvant properties of Pam3 CysSK4 , which can reduce the suppressive function of regulatory T cells and enhance the cytotoxicity of tumor-specific CTLs, 1219:1382 The unique adjuvant properties of Pam3 CysSK4 , which can reduce the suppressive function of regulatory T cells and enhance the cytotoxicity of tumor-specific CTLs, are likely responsible for the superior properties of the vaccine candidate 1. 24890740 1 19 link O-linked 261:268 arg1 saccharides 270:280 truncated O-linked saccharides 251:280 truncated O-linked saccharides 251:280 The mucin MUC1 is overexpressed and aberrantly glycosylated by many epithelial cancer cells manifested by truncated O-linked saccharides. 24890740 2 20 theme tumor-associated 292:307 arg1 MUC1 309:312 tumor-associated MUC1 292:312 tumor-associated MUC1 292:312 Although tumor-associated MUC1 has generated considerable attention because of its potential for the development of a therapeutic cancer vaccine, it has been difficult to design constructs that consistently induce cytotoxic T-lymphocytes (CTLs) and ADCC-mediating antibodies specific for the tumor form of MUC1. 24890740 6 21 theme candidate 1450:1458 arg1 properties 1424:1433 the superior properties 1411:1433 the superior properties of the vaccine candidate 1 1411:1460 The unique adjuvant properties of Pam3 CysSK4 , which can reduce the suppressive function of regulatory T cells and enhance the cytotoxicity of tumor-specific CTLs, are likely responsible for the superior properties of the vaccine candidate 1. 24890740 2 22 theme ADCC-mediating 532:545 arg1 antibodies 547:556 ADCC-mediating antibodies 532:556 ADCC-mediating antibodies specific for the tumor form of MUC1 532:592 Although tumor-associated MUC1 has generated considerable attention because of its potential for the development of a therapeutic cancer vaccine, it has been difficult to design constructs that consistently induce cytotoxic T-lymphocytes (CTLs) and ADCC-mediating antibodies specific for the tumor form of MUC1. 24890740 3 23 theme promiscuous 738:748 arg1 peptide 758:764 a promiscuous Thelper peptide 736:764 a promiscuous Thelper peptide 736:764 We have designed, chemically synthesized, and immunologically examined vaccine candidates each composed of a glycopeptide derived from MUC1, a promiscuous Thelper peptide, and a TLR2 (Pam3 CysSK4 ) or TLR9 (CpG-ODN 1826) agonist. 24890740 1 24 gly glycosylated 192:203 arg1 MUC1 155:158 The mucin MUC1 145:158 The mucin MUC1 145:158 The mucin MUC1 is overexpressed and aberrantly glycosylated by many epithelial cancer cells manifested by truncated O-linked saccharides. 24890740 3 25 dep candidates 674:683 arg1 each 685:688 each 685:688 each 685:688 We have designed, chemically synthesized, and immunologically examined vaccine candidates each composed of a glycopeptide derived from MUC1, a promiscuous Thelper peptide, and a TLR2 (Pam3 CysSK4 ) or TLR9 (CpG-ODN 1826) agonist. 24890740 2 26 theme vaccine 420:426 arg1 development 384:394 the development 380:394 the development of a therapeutic cancer vaccine 380:426 Although tumor-associated MUC1 has generated considerable attention because of its potential for the development of a therapeutic cancer vaccine, it has been difficult to design constructs that consistently induce cytotoxic T-lymphocytes (CTLs) and ADCC-mediating antibodies specific for the tumor form of MUC1. 24890740 3 27 attach derived 717:723 arg1 CpG-ODN 802:808 CpG-ODN 1826 802:813 CpG-ODN 1826 802:813 We have designed, chemically synthesized, and immunologically examined vaccine candidates each composed of a glycopeptide derived from MUC1, a promiscuous Thelper peptide, and a TLR2 (Pam3 CysSK4 ) or TLR9 (CpG-ODN 1826) agonist. 24890740 3 27 attach derived 717:723 arg1 peptide 758:764 a promiscuous Thelper peptide 736:764 a promiscuous Thelper peptide 736:764 We have designed, chemically synthesized, and immunologically examined vaccine candidates each composed of a glycopeptide derived from MUC1, a promiscuous Thelper peptide, and a TLR2 (Pam3 CysSK4 ) or TLR9 (CpG-ODN 1826) agonist. 24890740 3 27 attach derived 717:723 arg1 CysSK4 784:789 Pam3 CysSK4 779:789 Pam3 CysSK4 779:789 We have designed, chemically synthesized, and immunologically examined vaccine candidates each composed of a glycopeptide derived from MUC1, a promiscuous Thelper peptide, and a TLR2 (Pam3 CysSK4 ) or TLR9 (CpG-ODN 1826) agonist. 24890740 3 27 attach derived 717:723 arg2 glycopeptide 704:715 a glycopeptide 702:715 a glycopeptide derived from MUC1, a promiscuous Thelper peptide, and a TLR2 (Pam3 CysSK4 ) or TLR9 (CpG-ODN 1826) agonist 702:822 We have designed, chemically synthesized, and immunologically examined vaccine candidates each composed of a glycopeptide derived from MUC1, a promiscuous Thelper peptide, and a TLR2 (Pam3 CysSK4 ) or TLR9 (CpG-ODN 1826) agonist. 24890740 3 27 attach derived 717:723 arg1 MUC1 730:733 MUC1 730:733 MUC1 730:733 We have designed, chemically synthesized, and immunologically examined vaccine candidates each composed of a glycopeptide derived from MUC1, a promiscuous Thelper peptide, and a TLR2 (Pam3 CysSK4 ) or TLR9 (CpG-ODN 1826) agonist. 24890740 3 27 attach derived 717:723 arg1 TLR2 773:776 a TLR2 771:776 a TLR2 (Pam3 CysSK4 ) 771:791 We have designed, chemically synthesized, and immunologically examined vaccine candidates each composed of a glycopeptide derived from MUC1, a promiscuous Thelper peptide, and a TLR2 (Pam3 CysSK4 ) or TLR9 (CpG-ODN 1826) agonist. 24890740 3 28 theme Thelper 750:756 arg1 peptide 758:764 a promiscuous Thelper peptide 736:764 a promiscuous Thelper peptide 736:764 We have designed, chemically synthesized, and immunologically examined vaccine candidates each composed of a glycopeptide derived from MUC1, a promiscuous Thelper peptide, and a TLR2 (Pam3 CysSK4 ) or TLR9 (CpG-ODN 1826) agonist. 24890740 4 29 dep antigenic 900:908 arg1 potent 893:898 potent 893:898 potent 893:898 It was found that the Pam3 CysSK4 -containing compound elicits more potent antigenic and cellular immune responses, resulting in a therapeutic effect in a mouse model of mammary cancer. 24890740 2 30 theme cancer 413:418 arg1 vaccine 420:426 a therapeutic cancer vaccine 399:426 a therapeutic cancer vaccine 399:426 Although tumor-associated MUC1 has generated considerable attention because of its potential for the development of a therapeutic cancer vaccine, it has been difficult to design constructs that consistently induce cytotoxic T-lymphocytes (CTLs) and ADCC-mediating antibodies specific for the tumor form of MUC1. 24890740 0 31 theme Immune 0:5 arg1 responses 22:30 Immune and anticancer responses 0:30 Immune and anticancer responses elicited by fully synthetic aberrantly glycosylated MUC1 tripartite vaccines 0:107 Immune and anticancer responses elicited by fully synthetic aberrantly glycosylated MUC1 tripartite vaccines modified by a TLR2 or TLR9 agonist. 24890740 4 32 theme mammary 995:1001 arg1 cancer 1003:1008 mammary cancer 995:1008 mammary cancer 995:1008 It was found that the Pam3 CysSK4 -containing compound elicits more potent antigenic and cellular immune responses, resulting in a therapeutic effect in a mouse model of mammary cancer. 24890740 4 33 theme cancer 1003:1008 arg1 model 986:990 a mouse model 978:990 a mouse model of mammary cancer 978:1008 It was found that the Pam3 CysSK4 -containing compound elicits more potent antigenic and cellular immune responses, resulting in a therapeutic effect in a mouse model of mammary cancer. 24890740 2 34 theme therapeutic 401:411 arg1 vaccine 420:426 a therapeutic cancer vaccine 399:426 a therapeutic cancer vaccine 399:426 Although tumor-associated MUC1 has generated considerable attention because of its potential for the development of a therapeutic cancer vaccine, it has been difficult to design constructs that consistently induce cytotoxic T-lymphocytes (CTLs) and ADCC-mediating antibodies specific for the tumor form of MUC1. 24890740 2 35 theme design 454:459 arg1 constructs 461:470 design constructs 454:470 design constructs that consistently induce cytotoxic T-lymphocytes (CTLs) and ADCC-mediating antibodies specific for the tumor form of MUC1 454:592 Although tumor-associated MUC1 has generated considerable attention because of its potential for the development of a therapeutic cancer vaccine, it has been difficult to design constructs that consistently induce cytotoxic T-lymphocytes (CTLs) and ADCC-mediating antibodies specific for the tumor form of MUC1. 24890740 3 36 dep MUC1 730:733 arg1 agonist 816:822 agonist 816:822 agonist 816:822 We have designed, chemically synthesized, and immunologically examined vaccine candidates each composed of a glycopeptide derived from MUC1, a promiscuous Thelper peptide, and a TLR2 (Pam3 CysSK4 ) or TLR9 (CpG-ODN 1826) agonist. 24890740 4 37 theme cellular 914:921 arg1 responses 930:938 more potent antigenic and cellular immune responses 888:938 responses 930:938 It was found that the Pam3 CysSK4 -containing compound elicits more potent antigenic and cellular immune responses, resulting in a therapeutic effect in a mouse model of mammary cancer. 24890740 6 38 theme regulatory 1312:1321 arg1 cells 1325:1329 regulatory T cells 1312:1329 regulatory T cells 1312:1329 The unique adjuvant properties of Pam3 CysSK4 , which can reduce the suppressive function of regulatory T cells and enhance the cytotoxicity of tumor-specific CTLs, are likely responsible for the superior properties of the vaccine candidate 1. 24890740 2 39 theme considerable 328:339 arg1 attention 341:349 considerable attention 328:349 considerable attention 328:349 Although tumor-associated MUC1 has generated considerable attention because of its potential for the development of a therapeutic cancer vaccine, it has been difficult to design constructs that consistently induce cytotoxic T-lymphocytes (CTLs) and ADCC-mediating antibodies specific for the tumor form of MUC1. 24890740 0 40 theme anticancer 11:20 arg1 responses 22:30 Immune and anticancer responses 0:30 Immune and anticancer responses elicited by fully synthetic aberrantly glycosylated MUC1 tripartite vaccines 0:107 Immune and anticancer responses elicited by fully synthetic aberrantly glycosylated MUC1 tripartite vaccines modified by a TLR2 or TLR9 agonist. 24890740 0 41 theme TLR2 123:126 arg1 agonist 136:142 a TLR2 or TLR9 agonist 121:142 agonist 136:142 Immune and anticancer responses elicited by fully synthetic aberrantly glycosylated MUC1 tripartite vaccines modified by a TLR2 or TLR9 agonist. 24890740 2 42 theme tumor 575:579 arg1 form 581:584 the tumor form 571:584 the tumor form of MUC1 571:592 Although tumor-associated MUC1 has generated considerable attention because of its potential for the development of a therapeutic cancer vaccine, it has been difficult to design constructs that consistently induce cytotoxic T-lymphocytes (CTLs) and ADCC-mediating antibodies specific for the tumor form of MUC1. 24890740 5 43 theme first 1037:1041 arg1 time 1043:1046 the first time 1033:1046 the first time 1033:1046 It is thus shown, for the first time, that the nature of an inbuilt adjuvant of a tripartite vaccine can significantly impact the quality of immune responses elicited against a tumor-associated glycopeptide. 24890740 6 44 theme CysSK4 1258:1263 arg1 responsible 1395:1405 responsible 1395:1405 responsible 1395:1405 The unique adjuvant properties of Pam3 CysSK4 , which can reduce the suppressive function of regulatory T cells and enhance the cytotoxicity of tumor-specific CTLs, are likely responsible for the superior properties of the vaccine candidate 1. 24890740 6 44 theme CysSK4 1258:1263 arg1 properties 1239:1248 The unique adjuvant properties 1219:1248 The unique adjuvant properties of Pam3 CysSK4 , which can reduce the suppressive function of regulatory T cells and enhance the cytotoxicity of tumor-specific CTLs, 1219:1382 The unique adjuvant properties of Pam3 CysSK4 , which can reduce the suppressive function of regulatory T cells and enhance the cytotoxicity of tumor-specific CTLs, are likely responsible for the superior properties of the vaccine candidate 1. 24890740 1 45 theme many 208:211 arg1 cells 231:235 many epithelial cancer cells 208:235 many epithelial cancer cells manifested by truncated O-linked saccharides 208:280 The mucin MUC1 is overexpressed and aberrantly glycosylated by many epithelial cancer cells manifested by truncated O-linked saccharides. 24890740 2 46 theme cytotoxic 497:505 arg1 CTLs 522:525 CTLs 522:525 CTLs 522:525 Although tumor-associated MUC1 has generated considerable attention because of its potential for the development of a therapeutic cancer vaccine, it has been difficult to design constructs that consistently induce cytotoxic T-lymphocytes (CTLs) and ADCC-mediating antibodies specific for the tumor form of MUC1. 24890740 2 46 theme cytotoxic 497:505 arg1 T-lymphocytes 507:519 cytotoxic T-lymphocytes 497:519 cytotoxic T-lymphocytes (CTLs) 497:526 Although tumor-associated MUC1 has generated considerable attention because of its potential for the development of a therapeutic cancer vaccine, it has been difficult to design constructs that consistently induce cytotoxic T-lymphocytes (CTLs) and ADCC-mediating antibodies specific for the tumor form of MUC1. 24890740 0 47 theme TLR9 131:134 arg1 agonist 136:142 a TLR2 or TLR9 agonist 121:142 agonist 136:142 Immune and anticancer responses elicited by fully synthetic aberrantly glycosylated MUC1 tripartite vaccines modified by a TLR2 or TLR9 agonist. 24890740 3 48 theme vaccine 666:672 arg1 candidates 674:683 vaccine candidates 666:683 vaccine candidates each composed of a glycopeptide derived from MUC1, a promiscuous Thelper peptide, and a TLR2 (Pam3 CysSK4 ) or TLR9 (CpG-ODN 1826) agonist 666:822 We have designed, chemically synthesized, and immunologically examined vaccine candidates each composed of a glycopeptide derived from MUC1, a promiscuous Thelper peptide, and a TLR2 (Pam3 CysSK4 ) or TLR9 (CpG-ODN 1826) agonist. 24890740 5 49 theme tumor-associated 1188:1203 arg1 glycopeptide 1205:1216 a tumor-associated glycopeptide 1186:1216 a tumor-associated glycopeptide 1186:1216 It is thus shown, for the first time, that the nature of an inbuilt adjuvant of a tripartite vaccine can significantly impact the quality of immune responses elicited against a tumor-associated glycopeptide. 24890740 1 50 theme epithelial 213:222 arg1 cells 231:235 many epithelial cancer cells 208:235 many epithelial cancer cells manifested by truncated O-linked saccharides 208:280 The mucin MUC1 is overexpressed and aberrantly glycosylated by many epithelial cancer cells manifested by truncated O-linked saccharides. 24890740 0 51 theme synthetic 50:58 arg1 vaccines 100:107 fully synthetic aberrantly glycosylated MUC1 tripartite vaccines 44:107 fully synthetic aberrantly glycosylated MUC1 tripartite vaccines 44:107 Immune and anticancer responses elicited by fully synthetic aberrantly glycosylated MUC1 tripartite vaccines modified by a TLR2 or TLR9 agonist. 24890740 5 52 theme tripartite 1093:1102 arg1 vaccine 1104:1110 a tripartite vaccine 1091:1110 a tripartite vaccine 1091:1110 It is thus shown, for the first time, that the nature of an inbuilt adjuvant of a tripartite vaccine can significantly impact the quality of immune responses elicited against a tumor-associated glycopeptide. 24890740 6 53 theme suppressive 1288:1298 arg1 function 1300:1307 the suppressive function 1284:1307 the suppressive function of regulatory T cells 1284:1329 The unique adjuvant properties of Pam3 CysSK4 , which can reduce the suppressive function of regulatory T cells and enhance the cytotoxicity of tumor-specific CTLs, are likely responsible for the superior properties of the vaccine candidate 1. 24890740 4 54 theme immune 923:928 arg1 responses 930:938 more potent antigenic and cellular immune responses 888:938 responses 930:938 It was found that the Pam3 CysSK4 -containing compound elicits more potent antigenic and cellular immune responses, resulting in a therapeutic effect in a mouse model of mammary cancer. 24890740 3 55 theme Pam3 779:782 arg1 TLR2 773:776 a TLR2 771:776 a TLR2 (Pam3 CysSK4 ) 771:791 We have designed, chemically synthesized, and immunologically examined vaccine candidates each composed of a glycopeptide derived from MUC1, a promiscuous Thelper peptide, and a TLR2 (Pam3 CysSK4 ) or TLR9 (CpG-ODN 1826) agonist. 24890740 3 55 theme Pam3 779:782 arg1 CysSK4 784:789 Pam3 CysSK4 779:789 Pam3 CysSK4 779:789 We have designed, chemically synthesized, and immunologically examined vaccine candidates each composed of a glycopeptide derived from MUC1, a promiscuous Thelper peptide, and a TLR2 (Pam3 CysSK4 ) or TLR9 (CpG-ODN 1826) agonist. 24890740 6 56 theme unique 1223:1228 arg1 responsible 1395:1405 responsible 1395:1405 responsible 1395:1405 The unique adjuvant properties of Pam3 CysSK4 , which can reduce the suppressive function of regulatory T cells and enhance the cytotoxicity of tumor-specific CTLs, are likely responsible for the superior properties of the vaccine candidate 1. 24890740 6 56 theme unique 1223:1228 arg1 properties 1239:1248 The unique adjuvant properties 1219:1248 The unique adjuvant properties of Pam3 CysSK4 , which can reduce the suppressive function of regulatory T cells and enhance the cytotoxicity of tumor-specific CTLs, 1219:1382 The unique adjuvant properties of Pam3 CysSK4 , which can reduce the suppressive function of regulatory T cells and enhance the cytotoxicity of tumor-specific CTLs, are likely responsible for the superior properties of the vaccine candidate 1. 24890740 1 57 theme cancer 224:229 arg1 cells 231:235 many epithelial cancer cells 208:235 many epithelial cancer cells manifested by truncated O-linked saccharides 208:280 The mucin MUC1 is overexpressed and aberrantly glycosylated by many epithelial cancer cells manifested by truncated O-linked saccharides. 24890740 2 58 theme MUC1 589:592 arg1 form 581:584 the tumor form 571:584 the tumor form of MUC1 571:592 Although tumor-associated MUC1 has generated considerable attention because of its potential for the development of a therapeutic cancer vaccine, it has been difficult to design constructs that consistently induce cytotoxic T-lymphocytes (CTLs) and ADCC-mediating antibodies specific for the tumor form of MUC1. 24890740 6 59 theme cells 1325:1329 arg1 function 1300:1307 the suppressive function 1284:1307 the suppressive function of regulatory T cells 1284:1329 The unique adjuvant properties of Pam3 CysSK4 , which can reduce the suppressive function of regulatory T cells and enhance the cytotoxicity of tumor-specific CTLs, are likely responsible for the superior properties of the vaccine candidate 1. 24890740 3 60 gly glycopeptide 704:715 arg2 glycopeptide 704:715 a glycopeptide 702:715 a glycopeptide derived from MUC1, a promiscuous Thelper peptide, and a TLR2 (Pam3 CysSK4 ) or TLR9 (CpG-ODN 1826) agonist 702:822 We have designed, chemically synthesized, and immunologically examined vaccine candidates each composed of a glycopeptide derived from MUC1, a promiscuous Thelper peptide, and a TLR2 (Pam3 CysSK4 ) or TLR9 (CpG-ODN 1826) agonist. 24890740 0 61 theme glycosylated 71:82 arg1 vaccines 100:107 fully synthetic aberrantly glycosylated MUC1 tripartite vaccines 44:107 fully synthetic aberrantly glycosylated MUC1 tripartite vaccines 44:107 Immune and anticancer responses elicited by fully synthetic aberrantly glycosylated MUC1 tripartite vaccines modified by a TLR2 or TLR9 agonist. 24890740 6 62 theme tumor-specific 1363:1376 arg1 CTLs 1378:1381 tumor-specific CTLs 1363:1381 tumor-specific CTLs 1363:1381 The unique adjuvant properties of Pam3 CysSK4 , which can reduce the suppressive function of regulatory T cells and enhance the cytotoxicity of tumor-specific CTLs, are likely responsible for the superior properties of the vaccine candidate 1. 24890740 6 63 theme vaccine 1442:1448 arg1 candidate 1450:1458 the vaccine candidate 1 1438:1460 the vaccine candidate 1 1438:1460 The unique adjuvant properties of Pam3 CysSK4 , which can reduce the suppressive function of regulatory T cells and enhance the cytotoxicity of tumor-specific CTLs, are likely responsible for the superior properties of the vaccine candidate 1. 24890740 4 64 from effect 968:973 arg1 model 986:990 a mouse model 978:990 a mouse model of mammary cancer 978:1008 It was found that the Pam3 CysSK4 -containing compound elicits more potent antigenic and cellular immune responses, resulting in a therapeutic effect in a mouse model of mammary cancer. 24890740 4 65 theme therapeutic 956:966 arg1 effect 968:973 a therapeutic effect 954:973 a therapeutic effect in a mouse model of mammary cancer 954:1008 It was found that the Pam3 CysSK4 -containing compound elicits more potent antigenic and cellular immune responses, resulting in a therapeutic effect in a mouse model of mammary cancer. 24890740 5 66 theme immune 1152:1157 arg1 responses 1159:1167 immune responses 1152:1167 immune responses elicited against a tumor-associated glycopeptide 1152:1216 It is thus shown, for the first time, that the nature of an inbuilt adjuvant of a tripartite vaccine can significantly impact the quality of immune responses elicited against a tumor-associated glycopeptide. 24573683 8 0 theme CHO 1009:1011 arg1 cells 1014:1018 Lec8 Chinese hamster ovary (CHO) cells 981:1018 Lec8 Chinese hamster ovary (CHO) cells that lack UDP-Gal transporter activity and express GlcNAc-terminating, complex N-glycans 981:1107 We found that CTD110.6 binds not only to O-GlcNAc on proteins but also to terminal β-GlcNAc on the complex N-glycans of Lec8 Chinese hamster ovary (CHO) cells that lack UDP-Gal transporter activity and express GlcNAc-terminating, complex N-glycans. 24573683 11 1 theme EOGT 1457:1460 arg1 cDNA 1462:1465 a human EOGT cDNA 1449:1465 a human EOGT cDNA 1449:1465 Knockdown of CHO Eogt reduced binding of CTD110.6 to Lec1 CHO cells, and expression of a human EOGT cDNA increased the O-GlcNAc signal on Lec1 cells and the extracellular domain of NOTCH1. 24573683 8 2 theme cells 1014:1018 arg1 N-glycans 968:976 the complex N-glycans 956:976 the complex N-glycans of Lec8 Chinese hamster ovary (CHO) cells that lack UDP-Gal transporter activity and express GlcNAc-terminating, complex N-glycans 956:1107 We found that CTD110.6 binds not only to O-GlcNAc on proteins but also to terminal β-GlcNAc on the complex N-glycans of Lec8 Chinese hamster ovary (CHO) cells that lack UDP-Gal transporter activity and express GlcNAc-terminating, complex N-glycans. 24573683 10 3 theme Cell 1223:1226 arg1 glycoproteins 1236:1248 Cell surface glycoproteins 1223:1248 Cell surface glycoproteins recognized by CTD110.6 antibody 1223:1280 Cell surface glycoproteins recognized by CTD110.6 antibody included NOTCH1 that possesses many EGF repeats with a consensus site for EOGT. 24573683 3 4 theme nuclear 544:550 arg1 extracts 552:559 cytosolic and nuclear extracts 530:559 cytosolic and nuclear extracts 530:559 A number of antibodies that detect O-GlcNAc in cytosolic and nuclear extracts have been described previously. 24573683 7 5 theme O-GlcNAc 730:737 arg1 modification 739:750 the O-GlcNAc modification 726:750 the O-GlcNAc modification 726:750 D6 (#14) for detection of the O-GlcNAc modification on extracellular domains of membrane or secreted glycoproteins that may also carry various N- and O-glycans. 24573683 11 6 theme O-GlcNAc 1481:1488 arg1 signal 1490:1495 the O-GlcNAc signal 1477:1495 the O-GlcNAc signal on Lec1 cells 1477:1509 Knockdown of CHO Eogt reduced binding of CTD110.6 to Lec1 CHO cells, and expression of a human EOGT cDNA increased the O-GlcNAc signal on Lec1 cells and the extracellular domain of NOTCH1. 24573683 3 7 theme cytosolic 530:538 arg1 extracts 552:559 cytosolic and nuclear extracts 530:559 cytosolic and nuclear extracts 530:559 A number of antibodies that detect O-GlcNAc in cytosolic and nuclear extracts have been described previously. 24573683 8 8 theme transporter 1038:1048 arg1 activity 1050:1057 UDP-Gal transporter activity 1030:1057 UDP-Gal transporter activity 1030:1057 We found that CTD110.6 binds not only to O-GlcNAc on proteins but also to terminal β-GlcNAc on the complex N-glycans of Lec8 Chinese hamster ovary (CHO) cells that lack UDP-Gal transporter activity and express GlcNAc-terminating, complex N-glycans. 24573683 10 9 contain possesses 1303:1311 arg2 repeats 1322:1328 many EGF repeats 1313:1328 many EGF repeats 1313:1328 Cell surface glycoproteins recognized by CTD110.6 antibody included NOTCH1 that possesses many EGF repeats with a consensus site for EOGT. 24573683 10 9 contain possesses 1303:1311 arg1 NOTCH1 1291:1296 NOTCH1 1291:1296 NOTCH1 that possesses many EGF repeats with a consensus site for EOGT 1291:1359 Cell surface glycoproteins recognized by CTD110.6 antibody included NOTCH1 that possesses many EGF repeats with a consensus site for EOGT. 24573683 8 10 theme GlcNAc-terminating 1071:1088 arg1 N-glycans 1099:1107 GlcNAc-terminating, complex N-glycans 1071:1107 GlcNAc-terminating, complex N-glycans 1071:1107 We found that CTD110.6 binds not only to O-GlcNAc on proteins but also to terminal β-GlcNAc on the complex N-glycans of Lec8 Chinese hamster ovary (CHO) cells that lack UDP-Gal transporter activity and express GlcNAc-terminating, complex N-glycans. 24573683 5 11 dep 9D1 679:681 arg1 # 674:674 #3 674:675 #3 674:675 C7(#3), 9D1. 24573683 5 11 dep 9D1 679:681 arg1 C7 671:672 C7 671:672 C7(#3) 671:676 C7(#3), 9D1. 24573683 1 12 theme N-acetylglucosamine 131:149 arg1 modification 245:256 a well known post-translational modification 213:256 a well known post-translational modification that is catalyzed by the O-GlcNAc transferase OGT 213:306 The transfer of N-acetylglucosamine (GlcNAc) to Ser or Thr in cytoplasmic and nuclear proteins is a well known post-translational modification that is catalyzed by the O-GlcNAc transferase OGT. 24573683 1 12 theme N-acetylglucosamine 131:149 arg1 transfer 119:126 The transfer 115:126 The transfer of N-acetylglucosamine (GlcNAc) to Ser or Thr in cytoplasmic and nuclear proteins 115:208 The transfer of N-acetylglucosamine (GlcNAc) to Ser or Thr in cytoplasmic and nuclear proteins is a well known post-translational modification that is catalyzed by the O-GlcNAc transferase OGT. 24573683 11 13 from domain 1533:1538 arg1 cells 1505:1509 Lec1 cells 1500:1509 Lec1 cells 1500:1509 Knockdown of CHO Eogt reduced binding of CTD110.6 to Lec1 CHO cells, and expression of a human EOGT cDNA increased the O-GlcNAc signal on Lec1 cells and the extracellular domain of NOTCH1. 24573683 1 14 from Thr 170:172 arg1 proteins 201:208 cytoplasmic and nuclear proteins 177:208 cytoplasmic and nuclear proteins 177:208 The transfer of N-acetylglucosamine (GlcNAc) to Ser or Thr in cytoplasmic and nuclear proteins is a well known post-translational modification that is catalyzed by the O-GlcNAc transferase OGT. 24573683 8 15 from β-GlcNAc 944:951 arg1 N-glycans 968:976 the complex N-glycans 956:976 the complex N-glycans of Lec8 Chinese hamster ovary (CHO) cells that lack UDP-Gal transporter activity and express GlcNAc-terminating, complex N-glycans 956:1107 We found that CTD110.6 binds not only to O-GlcNAc on proteins but also to terminal β-GlcNAc on the complex N-glycans of Lec8 Chinese hamster ovary (CHO) cells that lack UDP-Gal transporter activity and express GlcNAc-terminating, complex N-glycans. 24573683 12 16 dep antibodies 1580:1589 arg1 IgM 1601:1603 IgM 1601:1603 IgM 1601:1603 Thus, with careful controls, antibodies CTD110.6 (IgM), #3 (IgG), and #10 (IgG) can be used to detect membrane and secreted proteins modified by O-GlcNAc on EGF repeats. 24573683 12 16 dep antibodies 1580:1589 arg1 CTD110.6 1591:1598 CTD110.6 1591:1598 CTD110.6 1591:1598 Thus, with careful controls, antibodies CTD110.6 (IgM), #3 (IgG), and #10 (IgG) can be used to detect membrane and secreted proteins modified by O-GlcNAc on EGF repeats. 24573683 0 17 theme cell 87:90 arg1 glycoproteins 100:112 cell surface glycoproteins 87:112 cell surface glycoproteins 87:112 Antibodies that detect O-linked β-D-N-acetylglucosamine on the extracellular domain of cell surface glycoproteins. 24573683 1 18 from Ser 163:165 arg1 proteins 201:208 cytoplasmic and nuclear proteins 177:208 cytoplasmic and nuclear proteins 177:208 The transfer of N-acetylglucosamine (GlcNAc) to Ser or Thr in cytoplasmic and nuclear proteins is a well known post-translational modification that is catalyzed by the O-GlcNAc transferase OGT. 24573683 11 19 theme CHO 1375:1377 arg1 Eogt 1379:1382 CHO Eogt 1375:1382 CHO Eogt 1375:1382 Knockdown of CHO Eogt reduced binding of CTD110.6 to Lec1 CHO cells, and expression of a human EOGT cDNA increased the O-GlcNAc signal on Lec1 cells and the extracellular domain of NOTCH1. 24573683 0 20 theme glycoproteins 100:112 arg1 domain 77:82 the extracellular domain 59:82 the extracellular domain of cell surface glycoproteins 59:112 Antibodies that detect O-linked β-D-N-acetylglucosamine on the extracellular domain of cell surface glycoproteins. 24573683 0 20 theme glycoproteins 100:112 arg1 glycoproteins 100:112 cell surface glycoproteins 87:112 cell surface glycoproteins 87:112 Antibodies that detect O-linked β-D-N-acetylglucosamine on the extracellular domain of cell surface glycoproteins. 24573683 7 21 theme various 835:841 arg1 N- 843:844 various N- 835:844 various N- 835:844 D6 (#14) for detection of the O-GlcNAc modification on extracellular domains of membrane or secreted glycoproteins that may also carry various N- and O-glycans. 24573683 2 22 theme factor-like 456:466 arg1 repeats 474:480 epidermal growth factor-like (EGF) repeats 439:480 epidermal growth factor-like (EGF) repeats 439:480 A more recently identified O-GlcNAc transferase, EOGT, functions in the secretory pathway and transfers O-GlcNAc to proteins with epidermal growth factor-like (EGF) repeats. 24573683 10 23 theme EGF 1318:1320 arg1 repeats 1322:1328 many EGF repeats 1313:1328 many EGF repeats 1313:1328 Cell surface glycoproteins recognized by CTD110.6 antibody included NOTCH1 that possesses many EGF repeats with a consensus site for EOGT. 24573683 9 24 gly glycoproteins 1191:1203 arg1 glycoproteins 1191:1203 cell surface glycoproteins 1178:1203 cell surface glycoproteins bearing O-GlcNAc 1178:1220 We show that CTD110.6, #3, and #10 antibodies can be used to detect cell surface glycoproteins bearing O-GlcNAc. 24573683 2 25 theme secretory 381:389 arg1 pathway 391:397 the secretory pathway 377:397 the secretory pathway 377:397 A more recently identified O-GlcNAc transferase, EOGT, functions in the secretory pathway and transfers O-GlcNAc to proteins with epidermal growth factor-like (EGF) repeats. 24573683 8 26 dep GlcNAc-terminating 1071:1088 arg1 complex 1091:1097 complex 1091:1097 complex 1091:1097 We found that CTD110.6 binds not only to O-GlcNAc on proteins but also to terminal β-GlcNAc on the complex N-glycans of Lec8 Chinese hamster ovary (CHO) cells that lack UDP-Gal transporter activity and express GlcNAc-terminating, complex N-glycans. 24573683 2 27 theme epidermal 439:447 arg1 repeats 474:480 epidermal growth factor-like (EGF) repeats 439:480 epidermal growth factor-like (EGF) repeats 439:480 A more recently identified O-GlcNAc transferase, EOGT, functions in the secretory pathway and transfers O-GlcNAc to proteins with epidermal growth factor-like (EGF) repeats. 24573683 1 28 theme transferase 292:302 arg1 OGT 304:306 the O-GlcNAc transferase OGT 279:306 the O-GlcNAc transferase OGT 279:306 The transfer of N-acetylglucosamine (GlcNAc) to Ser or Thr in cytoplasmic and nuclear proteins is a well known post-translational modification that is catalyzed by the O-GlcNAc transferase OGT. 24573683 10 29 theme consensus 1337:1345 arg1 site 1347:1350 a consensus site 1335:1350 a consensus site for EOGT 1335:1359 Cell surface glycoproteins recognized by CTD110.6 antibody included NOTCH1 that possesses many EGF repeats with a consensus site for EOGT. 24573683 11 30 theme extracellular 1519:1531 arg1 NOTCH1 1543:1548 NOTCH1 1543:1548 NOTCH1 1543:1548 Knockdown of CHO Eogt reduced binding of CTD110.6 to Lec1 CHO cells, and expression of a human EOGT cDNA increased the O-GlcNAc signal on Lec1 cells and the extracellular domain of NOTCH1. 24573683 11 30 theme extracellular 1519:1531 arg1 domain 1533:1538 the extracellular domain 1515:1538 the extracellular domain of NOTCH1 1515:1548 Knockdown of CHO Eogt reduced binding of CTD110.6 to Lec1 CHO cells, and expression of a human EOGT cDNA increased the O-GlcNAc signal on Lec1 cells and the extracellular domain of NOTCH1. 24573683 9 31 theme surface 1183:1189 arg1 glycoproteins 1191:1203 cell surface glycoproteins 1178:1203 cell surface glycoproteins bearing O-GlcNAc 1178:1220 We show that CTD110.6, #3, and #10 antibodies can be used to detect cell surface glycoproteins bearing O-GlcNAc. 24573683 4 32 dep CTD110.6 636:643 arg1 18B10 665:669 18B10 665:669 18B10 665:669 Here we compare seven of these antibodies (CTD110.6, 10D8, RL2, HGAC85, 18B10. 24573683 4 32 dep CTD110.6 636:643 arg1 HGAC85 657:662 HGAC85 657:662 HGAC85 657:662 Here we compare seven of these antibodies (CTD110.6, 10D8, RL2, HGAC85, 18B10. 24573683 4 32 dep CTD110.6 636:643 arg1 RL2 652:654 RL2 652:654 RL2 652:654 Here we compare seven of these antibodies (CTD110.6, 10D8, RL2, HGAC85, 18B10. 24573683 4 32 dep CTD110.6 636:643 arg1 10D8 646:649 10D8 646:649 10D8 646:649 Here we compare seven of these antibodies (CTD110.6, 10D8, RL2, HGAC85, 18B10. 24573683 2 33 theme EGF 469:471 arg1 repeats 474:480 epidermal growth factor-like (EGF) repeats 439:480 epidermal growth factor-like (EGF) repeats 439:480 A more recently identified O-GlcNAc transferase, EOGT, functions in the secretory pathway and transfers O-GlcNAc to proteins with epidermal growth factor-like (EGF) repeats. 24573683 4 34 dep antibodies 624:633 arg1 CTD110.6 636:643 CTD110.6 636:643 CTD110.6 636:643 Here we compare seven of these antibodies (CTD110.6, 10D8, RL2, HGAC85, 18B10. 24573683 2 35 theme O-GlcNAc 336:343 arg1 transferase 345:355 A more recently identified O-GlcNAc transferase 309:355 A more recently identified O-GlcNAc transferase 309:355 A more recently identified O-GlcNAc transferase, EOGT, functions in the secretory pathway and transfers O-GlcNAc to proteins with epidermal growth factor-like (EGF) repeats. 24573683 2 35 theme O-GlcNAc 336:343 arg1 EOGT 358:361 EOGT 358:361 EOGT 358:361 A more recently identified O-GlcNAc transferase, EOGT, functions in the secretory pathway and transfers O-GlcNAc to proteins with epidermal growth factor-like (EGF) repeats. 24573683 7 36 theme glycoproteins 801:813 arg1 domains 769:775 extracellular domains 755:775 extracellular domains of membrane or secreted glycoproteins that may also carry various N- and O-glycans 755:858 D6 (#14) for detection of the O-GlcNAc modification on extracellular domains of membrane or secreted glycoproteins that may also carry various N- and O-glycans. 24573683 7 36 theme glycoproteins 801:813 arg1 membrane 780:787 membrane 780:787 membrane 780:787 D6 (#14) for detection of the O-GlcNAc modification on extracellular domains of membrane or secreted glycoproteins that may also carry various N- and O-glycans. 24573683 7 36 theme glycoproteins 801:813 arg1 glycoproteins 801:813 secreted glycoproteins 792:813 secreted glycoproteins that may also carry various N- and O-glycans 792:858 D6 (#14) for detection of the O-GlcNAc modification on extracellular domains of membrane or secreted glycoproteins that may also carry various N- and O-glycans. 24573683 8 37 theme Lec8 981:984 arg1 cells 1014:1018 Lec8 Chinese hamster ovary (CHO) cells 981:1018 Lec8 Chinese hamster ovary (CHO) cells that lack UDP-Gal transporter activity and express GlcNAc-terminating, complex N-glycans 981:1107 We found that CTD110.6 binds not only to O-GlcNAc on proteins but also to terminal β-GlcNAc on the complex N-glycans of Lec8 Chinese hamster ovary (CHO) cells that lack UDP-Gal transporter activity and express GlcNAc-terminating, complex N-glycans. 24573683 11 38 theme human 1451:1455 arg1 cDNA 1462:1465 a human EOGT cDNA 1449:1465 a human EOGT cDNA 1449:1465 Knockdown of CHO Eogt reduced binding of CTD110.6 to Lec1 CHO cells, and expression of a human EOGT cDNA increased the O-GlcNAc signal on Lec1 cells and the extracellular domain of NOTCH1. 24573683 1 39 theme post-translational 226:243 arg1 modification 245:256 a well known post-translational modification 213:256 a well known post-translational modification that is catalyzed by the O-GlcNAc transferase OGT 213:306 The transfer of N-acetylglucosamine (GlcNAc) to Ser or Thr in cytoplasmic and nuclear proteins is a well known post-translational modification that is catalyzed by the O-GlcNAc transferase OGT. 24573683 1 39 theme post-translational 226:243 arg1 transfer 119:126 The transfer 115:126 The transfer of N-acetylglucosamine (GlcNAc) to Ser or Thr in cytoplasmic and nuclear proteins 115:208 The transfer of N-acetylglucosamine (GlcNAc) to Ser or Thr in cytoplasmic and nuclear proteins is a well known post-translational modification that is catalyzed by the O-GlcNAc transferase OGT. 24573683 8 40 theme hamster 994:1000 arg1 cells 1014:1018 Lec8 Chinese hamster ovary (CHO) cells 981:1018 Lec8 Chinese hamster ovary (CHO) cells that lack UDP-Gal transporter activity and express GlcNAc-terminating, complex N-glycans 981:1107 We found that CTD110.6 binds not only to O-GlcNAc on proteins but also to terminal β-GlcNAc on the complex N-glycans of Lec8 Chinese hamster ovary (CHO) cells that lack UDP-Gal transporter activity and express GlcNAc-terminating, complex N-glycans. 24573683 12 41 theme EGF 1708:1710 arg1 repeats 1712:1718 EGF repeats 1708:1718 EGF repeats 1708:1718 Thus, with careful controls, antibodies CTD110.6 (IgM), #3 (IgG), and #10 (IgG) can be used to detect membrane and secreted proteins modified by O-GlcNAc on EGF repeats. 24573683 3 42 theme antibodies 495:504 arg1 number 485:490 A number 483:490 A number of antibodies that detect O-GlcNAc in cytosolic and nuclear extracts 483:559 A number of antibodies that detect O-GlcNAc in cytosolic and nuclear extracts have been described previously. 24573683 0 43 link O-linked 23:30 arg1 β-D-N-acetylglucosamine 32:54 O-linked β-D-N-acetylglucosamine 23:54 O-linked β-D-N-acetylglucosamine 23:54 Antibodies that detect O-linked β-D-N-acetylglucosamine on the extracellular domain of cell surface glycoproteins. 24573683 11 44 theme cDNA 1462:1465 arg1 expression 1435:1444 expression 1435:1444 expression of a human EOGT cDNA 1435:1465 Knockdown of CHO Eogt reduced binding of CTD110.6 to Lec1 CHO cells, and expression of a human EOGT cDNA increased the O-GlcNAc signal on Lec1 cells and the extracellular domain of NOTCH1. 24573683 10 45 theme surface 1228:1234 arg1 glycoproteins 1236:1248 Cell surface glycoproteins 1223:1248 Cell surface glycoproteins recognized by CTD110.6 antibody 1223:1280 Cell surface glycoproteins recognized by CTD110.6 antibody included NOTCH1 that possesses many EGF repeats with a consensus site for EOGT. 24573683 7 46 theme extracellular 755:767 arg1 domains 769:775 extracellular domains 755:775 extracellular domains of membrane or secreted glycoproteins that may also carry various N- and O-glycans 755:858 D6 (#14) for detection of the O-GlcNAc modification on extracellular domains of membrane or secreted glycoproteins that may also carry various N- and O-glycans. 24573683 7 46 theme extracellular 755:767 arg1 membrane 780:787 membrane 780:787 membrane 780:787 D6 (#14) for detection of the O-GlcNAc modification on extracellular domains of membrane or secreted glycoproteins that may also carry various N- and O-glycans. 24573683 7 46 theme extracellular 755:767 arg1 glycoproteins 801:813 secreted glycoproteins 792:813 secreted glycoproteins that may also carry various N- and O-glycans 792:858 D6 (#14) for detection of the O-GlcNAc modification on extracellular domains of membrane or secreted glycoproteins that may also carry various N- and O-glycans. 24573683 11 47 theme Lec1 1500:1503 arg1 cells 1505:1509 Lec1 cells 1500:1509 Lec1 cells 1500:1509 Knockdown of CHO Eogt reduced binding of CTD110.6 to Lec1 CHO cells, and expression of a human EOGT cDNA increased the O-GlcNAc signal on Lec1 cells and the extracellular domain of NOTCH1. 24573683 11 48 theme Eogt 1379:1382 arg1 Knockdown 1362:1370 Knockdown 1362:1370 Knockdown of CHO Eogt 1362:1382 Knockdown of CHO Eogt reduced binding of CTD110.6 to Lec1 CHO cells, and expression of a human EOGT cDNA increased the O-GlcNAc signal on Lec1 cells and the extracellular domain of NOTCH1. 24573683 7 49 theme modification 739:750 arg1 detection 713:721 detection 713:721 detection of the O-GlcNAc modification on extracellular domains of membrane or secreted glycoproteins that may also carry various N- and O-glycans 713:858 D6 (#14) for detection of the O-GlcNAc modification on extracellular domains of membrane or secreted glycoproteins that may also carry various N- and O-glycans. 24573683 2 50 with proteins 425:432 arg1 repeats 474:480 epidermal growth factor-like (EGF) repeats 439:480 epidermal growth factor-like (EGF) repeats 439:480 A more recently identified O-GlcNAc transferase, EOGT, functions in the secretory pathway and transfers O-GlcNAc to proteins with epidermal growth factor-like (EGF) repeats. 24573683 11 51 theme Lec1 1415:1418 arg1 cells 1424:1428 Lec1 CHO cells 1415:1428 Lec1 CHO cells 1415:1428 Knockdown of CHO Eogt reduced binding of CTD110.6 to Lec1 CHO cells, and expression of a human EOGT cDNA increased the O-GlcNAc signal on Lec1 cells and the extracellular domain of NOTCH1. 24573683 1 52 theme cytoplasmic 177:187 arg1 proteins 201:208 cytoplasmic and nuclear proteins 177:208 cytoplasmic and nuclear proteins 177:208 The transfer of N-acetylglucosamine (GlcNAc) to Ser or Thr in cytoplasmic and nuclear proteins is a well known post-translational modification that is catalyzed by the O-GlcNAc transferase OGT. 24573683 8 53 theme UDP-Gal 1030:1036 arg1 activity 1050:1057 UDP-Gal transporter activity 1030:1057 UDP-Gal transporter activity 1030:1057 We found that CTD110.6 binds not only to O-GlcNAc on proteins but also to terminal β-GlcNAc on the complex N-glycans of Lec8 Chinese hamster ovary (CHO) cells that lack UDP-Gal transporter activity and express GlcNAc-terminating, complex N-glycans. 24573683 12 54 theme careful 1562:1568 arg1 controls 1570:1577 careful controls 1562:1577 careful controls 1562:1577 Thus, with careful controls, antibodies CTD110.6 (IgM), #3 (IgG), and #10 (IgG) can be used to detect membrane and secreted proteins modified by O-GlcNAc on EGF repeats. 24573683 7 55 contain carry 829:833 arg2 O-glycans 850:858 O-glycans 850:858 O-glycans 850:858 D6 (#14) for detection of the O-GlcNAc modification on extracellular domains of membrane or secreted glycoproteins that may also carry various N- and O-glycans. 24573683 7 55 contain carry 829:833 arg2 N- 843:844 various N- 835:844 various N- 835:844 D6 (#14) for detection of the O-GlcNAc modification on extracellular domains of membrane or secreted glycoproteins that may also carry various N- and O-glycans. 24573683 7 55 contain carry 829:833 arg1 glycoproteins 801:813 secreted glycoproteins 792:813 secreted glycoproteins that may also carry various N- and O-glycans 792:858 D6 (#14) for detection of the O-GlcNAc modification on extracellular domains of membrane or secreted glycoproteins that may also carry various N- and O-glycans. 24573683 11 56 theme CTD110.6 1403:1410 arg1 binding 1392:1398 binding 1392:1398 binding of CTD110.6 to Lec1 CHO cells 1392:1428 Knockdown of CHO Eogt reduced binding of CTD110.6 to Lec1 CHO cells, and expression of a human EOGT cDNA increased the O-GlcNAc signal on Lec1 cells and the extracellular domain of NOTCH1. 24573683 1 57 theme nuclear 193:199 arg1 proteins 201:208 cytoplasmic and nuclear proteins 177:208 cytoplasmic and nuclear proteins 177:208 The transfer of N-acetylglucosamine (GlcNAc) to Ser or Thr in cytoplasmic and nuclear proteins is a well known post-translational modification that is catalyzed by the O-GlcNAc transferase OGT. 24573683 8 58 from O-GlcNAc 902:909 arg1 proteins 914:921 proteins 914:921 proteins 914:921 We found that CTD110.6 binds not only to O-GlcNAc on proteins but also to terminal β-GlcNAc on the complex N-glycans of Lec8 Chinese hamster ovary (CHO) cells that lack UDP-Gal transporter activity and express GlcNAc-terminating, complex N-glycans. 24573683 2 59 theme growth 449:454 arg1 repeats 474:480 epidermal growth factor-like (EGF) repeats 439:480 epidermal growth factor-like (EGF) repeats 439:480 A more recently identified O-GlcNAc transferase, EOGT, functions in the secretory pathway and transfers O-GlcNAc to proteins with epidermal growth factor-like (EGF) repeats. 24573683 4 60 theme antibodies 624:633 arg1 seven 609:613 seven 609:613 seven 609:613 Here we compare seven of these antibodies (CTD110.6, 10D8, RL2, HGAC85, 18B10. 24573683 4 60 theme antibodies 624:633 arg1 antibodies 624:633 these antibodies 618:633 these antibodies (CTD110.6, 10D8, RL2, HGAC85, 18B10 618:669 Here we compare seven of these antibodies (CTD110.6, 10D8, RL2, HGAC85, 18B10. 24573683 9 61 used used 1163:1166 arg2 antibodies 1145:1154 CTD110.6, #3, and #10 antibodies 1123:1154 CTD110.6, #3, and #10 antibodies 1123:1154 We show that CTD110.6, #3, and #10 antibodies can be used to detect cell surface glycoproteins bearing O-GlcNAc. 24573683 7 62 gly glycoproteins 801:813 arg1 glycoproteins 801:813 secreted glycoproteins 792:813 secreted glycoproteins that may also carry various N- and O-glycans 792:858 D6 (#14) for detection of the O-GlcNAc modification on extracellular domains of membrane or secreted glycoproteins that may also carry various N- and O-glycans. 24573683 9 63 theme CTD110.6 1123:1130 arg1 antibodies 1145:1154 CTD110.6, #3, and #10 antibodies 1123:1154 CTD110.6, #3, and #10 antibodies 1123:1154 We show that CTD110.6, #3, and #10 antibodies can be used to detect cell surface glycoproteins bearing O-GlcNAc. 24573683 9 64 theme # 1133:1133 arg1 antibodies 1145:1154 CTD110.6, #3, and #10 antibodies 1123:1154 CTD110.6, #3, and #10 antibodies 1123:1154 We show that CTD110.6, #3, and #10 antibodies can be used to detect cell surface glycoproteins bearing O-GlcNAc. 24573683 0 65 theme surface 92:98 arg1 glycoproteins 100:112 cell surface glycoproteins 87:112 cell surface glycoproteins 87:112 Antibodies that detect O-linked β-D-N-acetylglucosamine on the extracellular domain of cell surface glycoproteins. 24573683 12 66 theme membrane 1653:1660 arg1 proteins 1675:1682 membrane and secreted proteins 1653:1682 proteins 1675:1682 Thus, with careful controls, antibodies CTD110.6 (IgM), #3 (IgG), and #10 (IgG) can be used to detect membrane and secreted proteins modified by O-GlcNAc on EGF repeats. 24573683 12 67 used used 1638:1641 arg2 antibodies 1580:1589 antibodies CTD110.6 (IgM) 1580:1604 antibodies CTD110.6 (IgM) 1580:1604 Thus, with careful controls, antibodies CTD110.6 (IgM), #3 (IgG), and #10 (IgG) can be used to detect membrane and secreted proteins modified by O-GlcNAc on EGF repeats. 24573683 12 67 used used 1638:1641 arg2 # 1621:1621 #10 1621:1623 #10 1621:1623 Thus, with careful controls, antibodies CTD110.6 (IgM), #3 (IgG), and #10 (IgG) can be used to detect membrane and secreted proteins modified by O-GlcNAc on EGF repeats. 24573683 12 67 used used 1638:1641 arg2 IgG 1626:1628 IgG 1626:1628 IgG 1626:1628 Thus, with careful controls, antibodies CTD110.6 (IgM), #3 (IgG), and #10 (IgG) can be used to detect membrane and secreted proteins modified by O-GlcNAc on EGF repeats. 24573683 12 67 used used 1638:1641 arg2 # 1607:1607 #3 1607:1608 #3 (IgG) 1607:1614 Thus, with careful controls, antibodies CTD110.6 (IgM), #3 (IgG), and #10 (IgG) can be used to detect membrane and secreted proteins modified by O-GlcNAc on EGF repeats. 24573683 9 68 theme # 1141:1141 arg1 antibodies 1145:1154 CTD110.6, #3, and #10 antibodies 1123:1154 CTD110.6, #3, and #10 antibodies 1123:1154 We show that CTD110.6, #3, and #10 antibodies can be used to detect cell surface glycoproteins bearing O-GlcNAc. 24573683 12 69 theme secreted 1666:1673 arg1 proteins 1675:1682 membrane and secreted proteins 1653:1682 proteins 1675:1682 Thus, with careful controls, antibodies CTD110.6 (IgM), #3 (IgG), and #10 (IgG) can be used to detect membrane and secreted proteins modified by O-GlcNAc on EGF repeats. 24573683 8 70 theme terminal 935:942 arg1 β-GlcNAc 944:951 terminal β-GlcNAc 935:951 terminal β-GlcNAc on the complex N-glycans of Lec8 Chinese hamster ovary (CHO) cells that lack UDP-Gal transporter activity and express GlcNAc-terminating, complex N-glycans 935:1107 We found that CTD110.6 binds not only to O-GlcNAc on proteins but also to terminal β-GlcNAc on the complex N-glycans of Lec8 Chinese hamster ovary (CHO) cells that lack UDP-Gal transporter activity and express GlcNAc-terminating, complex N-glycans. 24573683 0 71 gly glycoproteins 100:112 arg1 glycoproteins 100:112 cell surface glycoproteins 87:112 cell surface glycoproteins 87:112 Antibodies that detect O-linked β-D-N-acetylglucosamine on the extracellular domain of cell surface glycoproteins. 24573683 11 72 from signal 1490:1495 arg1 cells 1505:1509 Lec1 cells 1500:1509 Lec1 cells 1500:1509 Knockdown of CHO Eogt reduced binding of CTD110.6 to Lec1 CHO cells, and expression of a human EOGT cDNA increased the O-GlcNAc signal on Lec1 cells and the extracellular domain of NOTCH1. 24573683 10 73 theme many 1313:1316 arg1 repeats 1322:1328 many EGF repeats 1313:1328 many EGF repeats 1313:1328 Cell surface glycoproteins recognized by CTD110.6 antibody included NOTCH1 that possesses many EGF repeats with a consensus site for EOGT. 24573683 0 74 theme O-linked 23:30 arg1 β-D-N-acetylglucosamine 32:54 O-linked β-D-N-acetylglucosamine 23:54 O-linked β-D-N-acetylglucosamine 23:54 Antibodies that detect O-linked β-D-N-acetylglucosamine on the extracellular domain of cell surface glycoproteins. 24573683 1 75 theme O-GlcNAc 283:290 arg1 OGT 304:306 the O-GlcNAc transferase OGT 279:306 the O-GlcNAc transferase OGT 279:306 The transfer of N-acetylglucosamine (GlcNAc) to Ser or Thr in cytoplasmic and nuclear proteins is a well known post-translational modification that is catalyzed by the O-GlcNAc transferase OGT. 24573683 9 76 theme cell 1178:1181 arg1 glycoproteins 1191:1203 cell surface glycoproteins 1178:1203 cell surface glycoproteins bearing O-GlcNAc 1178:1220 We show that CTD110.6, #3, and #10 antibodies can be used to detect cell surface glycoproteins bearing O-GlcNAc. 24573683 8 77 theme complex 960:966 arg1 N-glycans 968:976 the complex N-glycans 956:976 the complex N-glycans of Lec8 Chinese hamster ovary (CHO) cells that lack UDP-Gal transporter activity and express GlcNAc-terminating, complex N-glycans 956:1107 We found that CTD110.6 binds not only to O-GlcNAc on proteins but also to terminal β-GlcNAc on the complex N-glycans of Lec8 Chinese hamster ovary (CHO) cells that lack UDP-Gal transporter activity and express GlcNAc-terminating, complex N-glycans. 24573683 10 78 gly glycoproteins 1236:1248 arg1 glycoproteins 1236:1248 Cell surface glycoproteins 1223:1248 Cell surface glycoproteins recognized by CTD110.6 antibody 1223:1280 Cell surface glycoproteins recognized by CTD110.6 antibody included NOTCH1 that possesses many EGF repeats with a consensus site for EOGT. 24573683 0 79 theme extracellular 63:75 arg1 domain 77:82 the extracellular domain 59:82 the extracellular domain of cell surface glycoproteins 59:112 Antibodies that detect O-linked β-D-N-acetylglucosamine on the extracellular domain of cell surface glycoproteins. 24573683 0 79 theme extracellular 63:75 arg1 glycoproteins 100:112 cell surface glycoproteins 87:112 cell surface glycoproteins 87:112 Antibodies that detect O-linked β-D-N-acetylglucosamine on the extracellular domain of cell surface glycoproteins. 24573683 11 80 theme NOTCH1 1543:1548 arg1 signal 1490:1495 the O-GlcNAc signal 1477:1495 the O-GlcNAc signal on Lec1 cells 1477:1509 Knockdown of CHO Eogt reduced binding of CTD110.6 to Lec1 CHO cells, and expression of a human EOGT cDNA increased the O-GlcNAc signal on Lec1 cells and the extracellular domain of NOTCH1. 24573683 11 80 theme NOTCH1 1543:1548 arg1 NOTCH1 1543:1548 NOTCH1 1543:1548 NOTCH1 1543:1548 Knockdown of CHO Eogt reduced binding of CTD110.6 to Lec1 CHO cells, and expression of a human EOGT cDNA increased the O-GlcNAc signal on Lec1 cells and the extracellular domain of NOTCH1. 24573683 11 80 theme NOTCH1 1543:1548 arg1 domain 1533:1538 the extracellular domain 1515:1538 the extracellular domain of NOTCH1 1515:1548 Knockdown of CHO Eogt reduced binding of CTD110.6 to Lec1 CHO cells, and expression of a human EOGT cDNA increased the O-GlcNAc signal on Lec1 cells and the extracellular domain of NOTCH1. 24573683 7 81 from detection 713:721 arg1 domains 769:775 extracellular domains 755:775 extracellular domains of membrane or secreted glycoproteins that may also carry various N- and O-glycans 755:858 D6 (#14) for detection of the O-GlcNAc modification on extracellular domains of membrane or secreted glycoproteins that may also carry various N- and O-glycans. 24573683 7 81 from detection 713:721 arg1 membrane 780:787 membrane 780:787 membrane 780:787 D6 (#14) for detection of the O-GlcNAc modification on extracellular domains of membrane or secreted glycoproteins that may also carry various N- and O-glycans. 24573683 7 81 from detection 713:721 arg1 glycoproteins 801:813 secreted glycoproteins 792:813 secreted glycoproteins that may also carry various N- and O-glycans 792:858 D6 (#14) for detection of the O-GlcNAc modification on extracellular domains of membrane or secreted glycoproteins that may also carry various N- and O-glycans. 24573683 11 82 theme CHO 1420:1422 arg1 cells 1424:1428 Lec1 CHO cells 1415:1428 Lec1 CHO cells 1415:1428 Knockdown of CHO Eogt reduced binding of CTD110.6 to Lec1 CHO cells, and expression of a human EOGT cDNA increased the O-GlcNAc signal on Lec1 cells and the extracellular domain of NOTCH1. 24573683 7 83 theme secreted 792:799 arg1 glycoproteins 801:813 secreted glycoproteins 792:813 secreted glycoproteins that may also carry various N- and O-glycans 792:858 D6 (#14) for detection of the O-GlcNAc modification on extracellular domains of membrane or secreted glycoproteins that may also carry various N- and O-glycans. 24573683 8 84 theme Chinese 986:992 arg1 cells 1014:1018 Lec8 Chinese hamster ovary (CHO) cells 981:1018 Lec8 Chinese hamster ovary (CHO) cells that lack UDP-Gal transporter activity and express GlcNAc-terminating, complex N-glycans 981:1107 We found that CTD110.6 binds not only to O-GlcNAc on proteins but also to terminal β-GlcNAc on the complex N-glycans of Lec8 Chinese hamster ovary (CHO) cells that lack UDP-Gal transporter activity and express GlcNAc-terminating, complex N-glycans. 24573683 2 85 theme identified 325:334 arg1 transferase 345:355 A more recently identified O-GlcNAc transferase 309:355 A more recently identified O-GlcNAc transferase 309:355 A more recently identified O-GlcNAc transferase, EOGT, functions in the secretory pathway and transfers O-GlcNAc to proteins with epidermal growth factor-like (EGF) repeats. 24573683 2 85 theme identified 325:334 arg1 EOGT 358:361 EOGT 358:361 EOGT 358:361 A more recently identified O-GlcNAc transferase, EOGT, functions in the secretory pathway and transfers O-GlcNAc to proteins with epidermal growth factor-like (EGF) repeats. 24573683 7 86 theme membrane 780:787 arg1 domains 769:775 extracellular domains 755:775 extracellular domains of membrane or secreted glycoproteins that may also carry various N- and O-glycans 755:858 D6 (#14) for detection of the O-GlcNAc modification on extracellular domains of membrane or secreted glycoproteins that may also carry various N- and O-glycans. 24573683 7 86 theme membrane 780:787 arg1 membrane 780:787 membrane 780:787 membrane 780:787 D6 (#14) for detection of the O-GlcNAc modification on extracellular domains of membrane or secreted glycoproteins that may also carry various N- and O-glycans. 24573683 7 86 theme membrane 780:787 arg1 glycoproteins 801:813 secreted glycoproteins 792:813 secreted glycoproteins that may also carry various N- and O-glycans 792:858 D6 (#14) for detection of the O-GlcNAc modification on extracellular domains of membrane or secreted glycoproteins that may also carry various N- and O-glycans. 24573683 1 87 theme known 220:224 arg1 modification 245:256 a well known post-translational modification 213:256 a well known post-translational modification that is catalyzed by the O-GlcNAc transferase OGT 213:306 The transfer of N-acetylglucosamine (GlcNAc) to Ser or Thr in cytoplasmic and nuclear proteins is a well known post-translational modification that is catalyzed by the O-GlcNAc transferase OGT. 24573683 1 87 theme known 220:224 arg1 transfer 119:126 The transfer 115:126 The transfer of N-acetylglucosamine (GlcNAc) to Ser or Thr in cytoplasmic and nuclear proteins 115:208 The transfer of N-acetylglucosamine (GlcNAc) to Ser or Thr in cytoplasmic and nuclear proteins is a well known post-translational modification that is catalyzed by the O-GlcNAc transferase OGT. 24573683 8 88 theme ovary 1002:1006 arg1 cells 1014:1018 Lec8 Chinese hamster ovary (CHO) cells 981:1018 Lec8 Chinese hamster ovary (CHO) cells that lack UDP-Gal transporter activity and express GlcNAc-terminating, complex N-glycans 981:1107 We found that CTD110.6 binds not only to O-GlcNAc on proteins but also to terminal β-GlcNAc on the complex N-glycans of Lec8 Chinese hamster ovary (CHO) cells that lack UDP-Gal transporter activity and express GlcNAc-terminating, complex N-glycans. 24523346 0 0 theme mouse 65:69 arg1 hearts 71:76 mouse hearts 65:76 mouse hearts 65:76 Consuming a Western diet for two weeks suppresses fetal genes in mouse hearts. 24523346 7 1 theme control 1214:1220 arg1 diet 1222:1225 a Western (n = 12) or control diet 1192:1225 diet 1222:1225 Five-week-old male C57BL/6 mice were fed a Western (n = 12) or control diet (n = 12) for 2 wk to examine the early hypertrophic response. 24523346 7 2 theme Five-week-old 1151:1163 arg1 mice 1178:1181 Five-week-old male C57BL/6 mice 1151:1181 Five-week-old male C57BL/6 mice 1151:1181 Five-week-old male C57BL/6 mice were fed a Western (n = 12) or control diet (n = 12) for 2 wk to examine the early hypertrophic response. 24523346 11 3 theme blot 1566:1569 arg1 analysis 1571:1578 Western blot analysis 1558:1578 Western blot analysis 1558:1578 Western blot analysis showed that HDAC protein levels were not different between groups; however, relative to controls, Western diet hearts showed increased REST and decreased ANP and skeletal α-actin. 24523346 1 4 theme Western 118:124 arg1 fat 113:115 saturated fat 103:115 saturated fat (Western diet) 103:130 Diets high in sugar and saturated fat (Western diet) contribute to obesity and pathophysiology of metabolic syndrome. 24523346 1 4 theme Western 118:124 arg1 diet 126:129 Western diet 118:129 Western diet 118:129 Diets high in sugar and saturated fat (Western diet) contribute to obesity and pathophysiology of metabolic syndrome. 24523346 7 5 theme male 1165:1168 arg1 mice 1178:1181 Five-week-old male C57BL/6 mice 1151:1181 Five-week-old male C57BL/6 mice 1151:1181 Five-week-old male C57BL/6 mice were fed a Western (n = 12) or control diet (n = 12) for 2 wk to examine the early hypertrophic response. 24523346 13 6 theme hypertrophy 1914:1924 arg1 regulation 1887:1896 regulation 1887:1896 regulation of diet-induced hypertrophy 1887:1924 These data suggest that REST coordinates regulation of diet-induced hypertrophy at the level of chromatin. 24523346 3 7 theme fetal 486:490 arg1 program 505:511 a fetal cardiac gene program 484:511 a fetal cardiac gene program 484:511 Hypertrophy is regulated at the level of chromatin by repressor element 1-silencing transcription factor (REST), and pathological hypertrophy is associated with reexpression of a fetal cardiac gene program. 24523346 11 8 theme HDAC 1592:1595 arg1 levels 1605:1610 HDAC protein levels 1592:1610 HDAC protein levels 1592:1610 Western blot analysis showed that HDAC protein levels were not different between groups; however, relative to controls, Western diet hearts showed increased REST and decreased ANP and skeletal α-actin. 24523346 6 9 dep factor 1071:1076 arg1 REST/mammalian 1086:1099 complex REST/mammalian switch-independent 3A/histone deacetylase (HDAC) 1078:1148 the fetal gene-regulating transcription factor complex REST/mammalian switch-independent 3A/histone deacetylase (HDAC) 1031:1148 Therefore, we investigated the interactions between O-GlcNAc, OGT, and the fetal gene-regulating transcription factor complex REST/mammalian switch-independent 3A/histone deacetylase (HDAC). 24523346 8 10 theme fasting 1321:1327 arg1 hyperglycemia 1329:1341 fasting hyperglycemia 1321:1341 fasting hyperglycemia 1321:1341 Western diet-fed mice exhibited fasting hyperglycemia and increased body weight (P < 0.05). 24523346 6 11 dep REST/mammalian 1086:1099 arg1 HDAC 1144:1147 HDAC 1144:1147 HDAC 1144:1147 Therefore, we investigated the interactions between O-GlcNAc, OGT, and the fetal gene-regulating transcription factor complex REST/mammalian switch-independent 3A/histone deacetylase (HDAC). 24523346 6 11 dep REST/mammalian 1086:1099 arg1 deacetylase 1131:1141 switch-independent 3A/histone deacetylase 1101:1141 the fetal gene-regulating transcription factor complex REST/mammalian switch-independent 3A/histone deacetylase (HDAC) 1031:1148 Therefore, we investigated the interactions between O-GlcNAc, OGT, and the fetal gene-regulating transcription factor complex REST/mammalian switch-independent 3A/histone deacetylase (HDAC). 24523346 8 12 theme body 1357:1360 arg1 weight 1362:1367 increased body weight 1347:1367 increased body weight (P < 0.05) 1347:1378 Western diet-fed mice exhibited fasting hyperglycemia and increased body weight (P < 0.05). 24523346 8 12 theme body 1357:1360 arg1 < 1372:1372 P < 0.05 1370:1377 P < 0.05 1370:1377 Western diet-fed mice exhibited fasting hyperglycemia and increased body weight (P < 0.05). 24523346 1 13 from fat 113:115 arg1 high 85:88 high 85:88 high 85:88 Diets high in sugar and saturated fat (Western diet) contribute to obesity and pathophysiology of metabolic syndrome. 24523346 7 14 theme = 1230:1230 arg1 Western 1194:1200 a Western (n = 12) or control diet 1192:1225 Western 1194:1200 Five-week-old male C57BL/6 mice were fed a Western (n = 12) or control diet (n = 12) for 2 wk to examine the early hypertrophic response. 24523346 7 14 theme = 1230:1230 arg1 n 1228:1228 n = 12 1228:1233 n = 12 1228:1233 Five-week-old male C57BL/6 mice were fed a Western (n = 12) or control diet (n = 12) for 2 wk to examine the early hypertrophic response. 24523346 9 15 theme feeding 1420:1426 arg1 duration 1408:1415 this short duration 1397:1415 this short duration of feeding 1397:1426 As expected for this short duration of feeding, cardiac hypertrophy was not yet evident. 24523346 4 16 theme modification 709:720 arg1 O-GlcNAc 754:761 O-GlcNAc 754:761 O-GlcNAc 754:761 Reactivation of fetal genes is commonly observed in hypertension-induced hypertrophy; however, this response is blunted in diabetic hearts, partially due to upregulation of the posttranslational modification O-linked-β-N-acetylglucosamine (O-GlcNAc) to proteins by O-GlcNAc transferase (OGT). 24523346 4 16 theme modification 709:720 arg1 O-linked-β-N-acetylglucosamine 722:751 the posttranslational modification O-linked-β-N-acetylglucosamine 687:751 the posttranslational modification O-linked-β-N-acetylglucosamine (O-GlcNAc) to proteins 687:774 Reactivation of fetal genes is commonly observed in hypertension-induced hypertrophy; however, this response is blunted in diabetic hearts, partially due to upregulation of the posttranslational modification O-linked-β-N-acetylglucosamine (O-GlcNAc) to proteins by O-GlcNAc transferase (OGT). 24523346 7 17 theme = 1205:1205 arg1 Western 1194:1200 a Western (n = 12) or control diet 1192:1225 Western 1194:1200 Five-week-old male C57BL/6 mice were fed a Western (n = 12) or control diet (n = 12) for 2 wk to examine the early hypertrophic response. 24523346 7 17 theme = 1205:1205 arg1 n 1203:1203 n = 12 1203:1208 n = 12 1203:1208 Five-week-old male C57BL/6 mice were fed a Western (n = 12) or control diet (n = 12) for 2 wk to examine the early hypertrophic response. 24523346 3 18 dep element 371:377 arg1 REST 413:416 REST 413:416 REST 413:416 Hypertrophy is regulated at the level of chromatin by repressor element 1-silencing transcription factor (REST), and pathological hypertrophy is associated with reexpression of a fetal cardiac gene program. 24523346 3 18 dep element 371:377 arg1 factor 405:410 1-silencing transcription factor 379:410 repressor element 1-silencing transcription factor (REST) 361:417 Hypertrophy is regulated at the level of chromatin by repressor element 1-silencing transcription factor (REST), and pathological hypertrophy is associated with reexpression of a fetal cardiac gene program. 24523346 3 19 theme program 505:511 arg1 reexpression 468:479 reexpression 468:479 reexpression of a fetal cardiac gene program 468:511 Hypertrophy is regulated at the level of chromatin by repressor element 1-silencing transcription factor (REST), and pathological hypertrophy is associated with reexpression of a fetal cardiac gene program. 24523346 6 20 theme switch-independent 1101:1118 arg1 HDAC 1144:1147 HDAC 1144:1147 HDAC 1144:1147 Therefore, we investigated the interactions between O-GlcNAc, OGT, and the fetal gene-regulating transcription factor complex REST/mammalian switch-independent 3A/histone deacetylase (HDAC). 24523346 6 20 theme switch-independent 1101:1118 arg1 deacetylase 1131:1141 switch-independent 3A/histone deacetylase 1101:1141 the fetal gene-regulating transcription factor complex REST/mammalian switch-independent 3A/histone deacetylase (HDAC) 1031:1148 Therefore, we investigated the interactions between O-GlcNAc, OGT, and the fetal gene-regulating transcription factor complex REST/mammalian switch-independent 3A/histone deacetylase (HDAC). 24523346 4 21 theme hypertension-induced 566:585 arg1 hypertrophy 587:597 hypertension-induced hypertrophy 566:597 hypertension-induced hypertrophy 566:597 Reactivation of fetal genes is commonly observed in hypertension-induced hypertrophy; however, this response is blunted in diabetic hearts, partially due to upregulation of the posttranslational modification O-linked-β-N-acetylglucosamine (O-GlcNAc) to proteins by O-GlcNAc transferase (OGT). 24523346 12 22 theme diet 1833:1836 arg1 hearts 1838:1843 Western diet hearts 1825:1843 Western diet hearts 1825:1843 Transcript levels of HDAC2 and cardiac α-actin were decreased in Western diet hearts. 24523346 4 23 theme O-GlcNAc 779:786 arg1 OGT 801:803 OGT 801:803 OGT 801:803 Reactivation of fetal genes is commonly observed in hypertension-induced hypertrophy; however, this response is blunted in diabetic hearts, partially due to upregulation of the posttranslational modification O-linked-β-N-acetylglucosamine (O-GlcNAc) to proteins by O-GlcNAc transferase (OGT). 24523346 4 23 theme O-GlcNAc 779:786 arg1 transferase 788:798 O-GlcNAc transferase 779:798 O-GlcNAc transferase (OGT) 779:804 Reactivation of fetal genes is commonly observed in hypertension-induced hypertrophy; however, this response is blunted in diabetic hearts, partially due to upregulation of the posttranslational modification O-linked-β-N-acetylglucosamine (O-GlcNAc) to proteins by O-GlcNAc transferase (OGT). 24523346 6 24 theme 3A/histone 1120:1129 arg1 HDAC 1144:1147 HDAC 1144:1147 HDAC 1144:1147 Therefore, we investigated the interactions between O-GlcNAc, OGT, and the fetal gene-regulating transcription factor complex REST/mammalian switch-independent 3A/histone deacetylase (HDAC). 24523346 6 24 theme 3A/histone 1120:1129 arg1 deacetylase 1131:1141 switch-independent 3A/histone deacetylase 1101:1141 the fetal gene-regulating transcription factor complex REST/mammalian switch-independent 3A/histone deacetylase (HDAC) 1031:1148 Therefore, we investigated the interactions between O-GlcNAc, OGT, and the fetal gene-regulating transcription factor complex REST/mammalian switch-independent 3A/histone deacetylase (HDAC). 24523346 4 25 theme diabetic 637:644 arg1 hearts 646:651 diabetic hearts 637:651 diabetic hearts 637:651 Reactivation of fetal genes is commonly observed in hypertension-induced hypertrophy; however, this response is blunted in diabetic hearts, partially due to upregulation of the posttranslational modification O-linked-β-N-acetylglucosamine (O-GlcNAc) to proteins by O-GlcNAc transferase (OGT). 24523346 11 26 theme skeletal 1742:1749 arg1 α-actin 1751:1757 skeletal α-actin 1742:1757 skeletal α-actin 1742:1757 Western blot analysis showed that HDAC protein levels were not different between groups; however, relative to controls, Western diet hearts showed increased REST and decreased ANP and skeletal α-actin. 24523346 5 27 theme diet-induced 922:933 arg1 remodeling 948:957 Western diet-induced hypertrophic remodeling 914:957 Western diet-induced hypertrophic remodeling 914:957 OGT and O-GlcNAc are found in chromatin-modifying complexes, but it is unknown whether they play a role in Western diet-induced hypertrophic remodeling. 24523346 6 28 theme complex 1078:1084 arg1 REST/mammalian 1086:1099 complex REST/mammalian switch-independent 3A/histone deacetylase (HDAC) 1078:1148 the fetal gene-regulating transcription factor complex REST/mammalian switch-independent 3A/histone deacetylase (HDAC) 1031:1148 Therefore, we investigated the interactions between O-GlcNAc, OGT, and the fetal gene-regulating transcription factor complex REST/mammalian switch-independent 3A/histone deacetylase (HDAC). 24523346 3 29 theme repressor 361:369 arg1 element 371:377 repressor element 1-silencing transcription factor (REST) 361:417 repressor element 1-silencing transcription factor (REST) 361:417 Hypertrophy is regulated at the level of chromatin by repressor element 1-silencing transcription factor (REST), and pathological hypertrophy is associated with reexpression of a fetal cardiac gene program. 24523346 4 30 theme genes 536:540 arg1 Reactivation 514:525 Reactivation 514:525 Reactivation of fetal genes 514:540 Reactivation of fetal genes is commonly observed in hypertension-induced hypertrophy; however, this response is blunted in diabetic hearts, partially due to upregulation of the posttranslational modification O-linked-β-N-acetylglucosamine (O-GlcNAc) to proteins by O-GlcNAc transferase (OGT). 24523346 13 31 theme chromatin 1942:1950 arg1 level 1933:1937 the level 1929:1937 the level of chromatin 1929:1950 These data suggest that REST coordinates regulation of diet-induced hypertrophy at the level of chromatin. 24523346 5 32 theme hypertrophic 935:946 arg1 remodeling 948:957 Western diet-induced hypertrophic remodeling 914:957 Western diet-induced hypertrophic remodeling 914:957 OGT and O-GlcNAc are found in chromatin-modifying complexes, but it is unknown whether they play a role in Western diet-induced hypertrophic remodeling. 24523346 10 33 theme mouse 1544:1548 arg1 hearts 1550:1555 mouse hearts 1544:1555 mouse hearts 1544:1555 We found that REST is O-GlcNAcylated and physically interacts with OGT in mouse hearts. 24523346 4 34 theme fetal 530:534 arg1 genes 536:540 fetal genes 530:540 fetal genes 530:540 Reactivation of fetal genes is commonly observed in hypertension-induced hypertrophy; however, this response is blunted in diabetic hearts, partially due to upregulation of the posttranslational modification O-linked-β-N-acetylglucosamine (O-GlcNAc) to proteins by O-GlcNAc transferase (OGT). 24523346 1 35 from sugar 93:97 arg1 high 85:88 high 85:88 high 85:88 Diets high in sugar and saturated fat (Western diet) contribute to obesity and pathophysiology of metabolic syndrome. 24523346 2 36 theme cardiac 271:277 arg1 remodeling 279:288 cardiac remodeling 271:288 cardiac remodeling 271:288 A common physiological response to obesity is hypertension, which induces cardiac remodeling and hypertrophy. 24523346 6 37 theme transcription 1057:1069 arg1 factor 1071:1076 the fetal gene-regulating transcription factor 1031:1076 the fetal gene-regulating transcription factor complex REST/mammalian switch-independent 3A/histone deacetylase (HDAC) 1031:1148 Therefore, we investigated the interactions between O-GlcNAc, OGT, and the fetal gene-regulating transcription factor complex REST/mammalian switch-independent 3A/histone deacetylase (HDAC). 24523346 3 38 theme chromatin 348:356 arg1 level 339:343 the level 335:343 the level of chromatin 335:356 Hypertrophy is regulated at the level of chromatin by repressor element 1-silencing transcription factor (REST), and pathological hypertrophy is associated with reexpression of a fetal cardiac gene program. 24523346 1 39 theme high 85:88 arg1 Diets 79:83 Diets 79:83 Diets high in sugar and saturated fat (Western diet) 79:130 Diets high in sugar and saturated fat (Western diet) contribute to obesity and pathophysiology of metabolic syndrome. 24523346 6 40 theme gene-regulating 1041:1055 arg1 factor 1071:1076 the fetal gene-regulating transcription factor 1031:1076 the fetal gene-regulating transcription factor complex REST/mammalian switch-independent 3A/histone deacetylase (HDAC) 1031:1148 Therefore, we investigated the interactions between O-GlcNAc, OGT, and the fetal gene-regulating transcription factor complex REST/mammalian switch-independent 3A/histone deacetylase (HDAC). 24523346 3 41 theme transcription 391:403 arg1 REST 413:416 REST 413:416 REST 413:416 Hypertrophy is regulated at the level of chromatin by repressor element 1-silencing transcription factor (REST), and pathological hypertrophy is associated with reexpression of a fetal cardiac gene program. 24523346 3 41 theme transcription 391:403 arg1 factor 405:410 1-silencing transcription factor 379:410 repressor element 1-silencing transcription factor (REST) 361:417 Hypertrophy is regulated at the level of chromatin by repressor element 1-silencing transcription factor (REST), and pathological hypertrophy is associated with reexpression of a fetal cardiac gene program. 24523346 7 42 theme early 1260:1264 arg1 response 1279:1286 the early hypertrophic response 1256:1286 the early hypertrophic response 1256:1286 Five-week-old male C57BL/6 mice were fed a Western (n = 12) or control diet (n = 12) for 2 wk to examine the early hypertrophic response. 24523346 12 43 theme Western 1825:1831 arg1 hearts 1838:1843 Western diet hearts 1825:1843 Western diet hearts 1825:1843 Transcript levels of HDAC2 and cardiac α-actin were decreased in Western diet hearts. 24523346 6 44 theme fetal 1035:1039 arg1 factor 1071:1076 the fetal gene-regulating transcription factor 1031:1076 the fetal gene-regulating transcription factor complex REST/mammalian switch-independent 3A/histone deacetylase (HDAC) 1031:1148 Therefore, we investigated the interactions between O-GlcNAc, OGT, and the fetal gene-regulating transcription factor complex REST/mammalian switch-independent 3A/histone deacetylase (HDAC). 24523346 2 45 theme common 199:204 arg1 response 220:227 A common physiological response 197:227 A common physiological response to obesity 197:238 A common physiological response to obesity is hypertension, which induces cardiac remodeling and hypertrophy. 24523346 2 45 theme common 199:204 arg1 hypertension 243:254 hypertension 243:254 hypertension 243:254 A common physiological response to obesity is hypertension, which induces cardiac remodeling and hypertrophy. 24523346 5 46 theme chromatin-modifying 837:855 arg1 complexes 857:865 chromatin-modifying complexes 837:865 chromatin-modifying complexes 837:865 OGT and O-GlcNAc are found in chromatin-modifying complexes, but it is unknown whether they play a role in Western diet-induced hypertrophic remodeling. 24523346 0 47 theme Western 12:18 arg1 diet 20:23 a Western diet 10:23 a Western diet 10:23 Consuming a Western diet for two weeks suppresses fetal genes in mouse hearts. 24523346 8 48 theme P 1370:1370 arg1 weight 1362:1367 increased body weight 1347:1367 increased body weight (P < 0.05) 1347:1378 Western diet-fed mice exhibited fasting hyperglycemia and increased body weight (P < 0.05). 24523346 8 48 theme P 1370:1370 arg1 < 1372:1372 P < 0.05 1370:1377 P < 0.05 1370:1377 Western diet-fed mice exhibited fasting hyperglycemia and increased body weight (P < 0.05). 24523346 12 49 theme Transcript 1760:1769 arg1 levels 1771:1776 Transcript levels 1760:1776 Transcript levels of HDAC2 and cardiac α-actin 1760:1805 Transcript levels of HDAC2 and cardiac α-actin were decreased in Western diet hearts. 24523346 1 50 theme metabolic 177:185 arg1 syndrome 187:194 metabolic syndrome 177:194 metabolic syndrome 177:194 Diets high in sugar and saturated fat (Western diet) contribute to obesity and pathophysiology of metabolic syndrome. 24523346 7 51 theme C57BL/6 1170:1176 arg1 mice 1178:1181 Five-week-old male C57BL/6 mice 1151:1181 Five-week-old male C57BL/6 mice 1151:1181 Five-week-old male C57BL/6 mice were fed a Western (n = 12) or control diet (n = 12) for 2 wk to examine the early hypertrophic response. 24523346 11 52 dep showed 1698:1703 arg1 increased 1705:1713 increased 1705:1713 increased REST 1705:1718 Western blot analysis showed that HDAC protein levels were not different between groups; however, relative to controls, Western diet hearts showed increased REST and decreased ANP and skeletal α-actin. 24523346 11 52 dep showed 1698:1703 arg1 decreased 1724:1732 decreased 1724:1732 decreased ANP and skeletal α-actin 1724:1757 Western blot analysis showed that HDAC protein levels were not different between groups; however, relative to controls, Western diet hearts showed increased REST and decreased ANP and skeletal α-actin. 24523346 9 53 theme cardiac 1429:1435 arg1 hypertrophy 1437:1447 cardiac hypertrophy 1429:1447 cardiac hypertrophy 1429:1447 As expected for this short duration of feeding, cardiac hypertrophy was not yet evident. 24523346 8 54 theme increased 1347:1355 arg1 weight 1362:1367 increased body weight 1347:1367 increased body weight (P < 0.05) 1347:1378 Western diet-fed mice exhibited fasting hyperglycemia and increased body weight (P < 0.05). 24523346 8 54 theme increased 1347:1355 arg1 < 1372:1372 P < 0.05 1370:1377 P < 0.05 1370:1377 Western diet-fed mice exhibited fasting hyperglycemia and increased body weight (P < 0.05). 24523346 4 55 theme posttranslational 691:707 arg1 O-GlcNAc 754:761 O-GlcNAc 754:761 O-GlcNAc 754:761 Reactivation of fetal genes is commonly observed in hypertension-induced hypertrophy; however, this response is blunted in diabetic hearts, partially due to upregulation of the posttranslational modification O-linked-β-N-acetylglucosamine (O-GlcNAc) to proteins by O-GlcNAc transferase (OGT). 24523346 4 55 theme posttranslational 691:707 arg1 O-linked-β-N-acetylglucosamine 722:751 the posttranslational modification O-linked-β-N-acetylglucosamine 687:751 the posttranslational modification O-linked-β-N-acetylglucosamine (O-GlcNAc) to proteins 687:774 Reactivation of fetal genes is commonly observed in hypertension-induced hypertrophy; however, this response is blunted in diabetic hearts, partially due to upregulation of the posttranslational modification O-linked-β-N-acetylglucosamine (O-GlcNAc) to proteins by O-GlcNAc transferase (OGT). 24523346 3 56 theme 1-silencing 379:389 arg1 REST 413:416 REST 413:416 REST 413:416 Hypertrophy is regulated at the level of chromatin by repressor element 1-silencing transcription factor (REST), and pathological hypertrophy is associated with reexpression of a fetal cardiac gene program. 24523346 3 56 theme 1-silencing 379:389 arg1 factor 405:410 1-silencing transcription factor 379:410 repressor element 1-silencing transcription factor (REST) 361:417 Hypertrophy is regulated at the level of chromatin by repressor element 1-silencing transcription factor (REST), and pathological hypertrophy is associated with reexpression of a fetal cardiac gene program. 24523346 12 57 theme HDAC2 1781:1785 arg1 levels 1771:1776 Transcript levels 1760:1776 Transcript levels of HDAC2 and cardiac α-actin 1760:1805 Transcript levels of HDAC2 and cardiac α-actin were decreased in Western diet hearts. 24523346 8 58 theme diet-fed 1297:1304 arg1 mice 1306:1309 Western diet-fed mice 1289:1309 Western diet-fed mice 1289:1309 Western diet-fed mice exhibited fasting hyperglycemia and increased body weight (P < 0.05). 24523346 13 59 theme diet-induced 1901:1912 arg1 hypertrophy 1914:1924 diet-induced hypertrophy 1901:1924 diet-induced hypertrophy 1901:1924 These data suggest that REST coordinates regulation of diet-induced hypertrophy at the level of chromatin. 24523346 12 60 theme α-actin 1799:1805 arg1 levels 1771:1776 Transcript levels 1760:1776 Transcript levels of HDAC2 and cardiac α-actin 1760:1805 Transcript levels of HDAC2 and cardiac α-actin were decreased in Western diet hearts. 24523346 5 61 located found 828:832 arg1 complexes 857:865 chromatin-modifying complexes 837:865 chromatin-modifying complexes 837:865 OGT and O-GlcNAc are found in chromatin-modifying complexes, but it is unknown whether they play a role in Western diet-induced hypertrophic remodeling. 24523346 5 61 located found 828:832 arg2 O-GlcNAc 815:822 O-GlcNAc 815:822 O-GlcNAc 815:822 OGT and O-GlcNAc are found in chromatin-modifying complexes, but it is unknown whether they play a role in Western diet-induced hypertrophic remodeling. 24523346 5 61 located found 828:832 arg2 OGT 807:809 OGT 807:809 OGT 807:809 OGT and O-GlcNAc are found in chromatin-modifying complexes, but it is unknown whether they play a role in Western diet-induced hypertrophic remodeling. 24523346 4 62 located observed 554:561 arg1 hypertrophy 587:597 hypertension-induced hypertrophy 566:597 hypertension-induced hypertrophy 566:597 Reactivation of fetal genes is commonly observed in hypertension-induced hypertrophy; however, this response is blunted in diabetic hearts, partially due to upregulation of the posttranslational modification O-linked-β-N-acetylglucosamine (O-GlcNAc) to proteins by O-GlcNAc transferase (OGT). 24523346 4 62 located observed 554:561 arg2 Reactivation 514:525 Reactivation 514:525 Reactivation of fetal genes 514:540 Reactivation of fetal genes is commonly observed in hypertension-induced hypertrophy; however, this response is blunted in diabetic hearts, partially due to upregulation of the posttranslational modification O-linked-β-N-acetylglucosamine (O-GlcNAc) to proteins by O-GlcNAc transferase (OGT). 24523346 4 63 theme O-linked-β-N-acetylglucosamine 722:751 arg1 upregulation 671:682 upregulation 671:682 upregulation of the posttranslational modification O-linked-β-N-acetylglucosamine (O-GlcNAc) to proteins by O-GlcNAc transferase (OGT) 671:804 Reactivation of fetal genes is commonly observed in hypertension-induced hypertrophy; however, this response is blunted in diabetic hearts, partially due to upregulation of the posttranslational modification O-linked-β-N-acetylglucosamine (O-GlcNAc) to proteins by O-GlcNAc transferase (OGT). 24523346 1 64 from high 85:88 arg1 sugar 93:97 sugar 93:97 sugar 93:97 Diets high in sugar and saturated fat (Western diet) contribute to obesity and pathophysiology of metabolic syndrome. 24523346 1 64 from high 85:88 arg1 fat 113:115 saturated fat 103:115 saturated fat (Western diet) 103:130 Diets high in sugar and saturated fat (Western diet) contribute to obesity and pathophysiology of metabolic syndrome. 24523346 1 64 from high 85:88 arg1 diet 126:129 Western diet 118:129 Western diet 118:129 Diets high in sugar and saturated fat (Western diet) contribute to obesity and pathophysiology of metabolic syndrome. 24523346 1 65 theme syndrome 187:194 arg1 pathophysiology 158:172 pathophysiology 158:172 pathophysiology 158:172 Diets high in sugar and saturated fat (Western diet) contribute to obesity and pathophysiology of metabolic syndrome. 24523346 1 65 theme syndrome 187:194 arg1 obesity 146:152 obesity 146:152 obesity 146:152 Diets high in sugar and saturated fat (Western diet) contribute to obesity and pathophysiology of metabolic syndrome. 24523346 12 66 theme cardiac 1791:1797 arg1 α-actin 1799:1805 cardiac α-actin 1791:1805 cardiac α-actin 1791:1805 Transcript levels of HDAC2 and cardiac α-actin were decreased in Western diet hearts. 24523346 8 67 theme Western 1289:1295 arg1 mice 1306:1309 Western diet-fed mice 1289:1309 Western diet-fed mice 1289:1309 Western diet-fed mice exhibited fasting hyperglycemia and increased body weight (P < 0.05). 24523346 1 68 theme saturated 103:111 arg1 fat 113:115 saturated fat 103:115 saturated fat (Western diet) 103:130 Diets high in sugar and saturated fat (Western diet) contribute to obesity and pathophysiology of metabolic syndrome. 24523346 1 68 theme saturated 103:111 arg1 diet 126:129 Western diet 118:129 Western diet 118:129 Diets high in sugar and saturated fat (Western diet) contribute to obesity and pathophysiology of metabolic syndrome. 24523346 5 69 theme Western 914:920 arg1 remodeling 948:957 Western diet-induced hypertrophic remodeling 914:957 Western diet-induced hypertrophic remodeling 914:957 OGT and O-GlcNAc are found in chromatin-modifying complexes, but it is unknown whether they play a role in Western diet-induced hypertrophic remodeling. 24523346 3 70 theme pathological 424:435 arg1 hypertrophy 437:447 pathological hypertrophy 424:447 pathological hypertrophy 424:447 Hypertrophy is regulated at the level of chromatin by repressor element 1-silencing transcription factor (REST), and pathological hypertrophy is associated with reexpression of a fetal cardiac gene program. 24523346 7 71 theme hypertrophic 1266:1277 arg1 response 1279:1286 the early hypertrophic response 1256:1286 the early hypertrophic response 1256:1286 Five-week-old male C57BL/6 mice were fed a Western (n = 12) or control diet (n = 12) for 2 wk to examine the early hypertrophic response. 24523346 3 72 theme cardiac 492:498 arg1 program 505:511 a fetal cardiac gene program 484:511 a fetal cardiac gene program 484:511 Hypertrophy is regulated at the level of chromatin by repressor element 1-silencing transcription factor (REST), and pathological hypertrophy is associated with reexpression of a fetal cardiac gene program. 24523346 9 73 theme short 1402:1406 arg1 duration 1408:1415 this short duration 1397:1415 this short duration of feeding 1397:1426 As expected for this short duration of feeding, cardiac hypertrophy was not yet evident. 24523346 11 74 theme Western 1678:1684 arg1 hearts 1691:1696 Western diet hearts 1678:1696 Western diet hearts 1678:1696 Western blot analysis showed that HDAC protein levels were not different between groups; however, relative to controls, Western diet hearts showed increased REST and decreased ANP and skeletal α-actin. 24523346 0 75 theme fetal 50:54 arg1 genes 56:60 fetal genes 50:60 fetal genes 50:60 Consuming a Western diet for two weeks suppresses fetal genes in mouse hearts. 24523346 11 76 theme protein 1597:1603 arg1 levels 1605:1610 HDAC protein levels 1592:1610 HDAC protein levels 1592:1610 Western blot analysis showed that HDAC protein levels were not different between groups; however, relative to controls, Western diet hearts showed increased REST and decreased ANP and skeletal α-actin. 24523346 2 77 theme physiological 206:218 arg1 response 220:227 A common physiological response 197:227 A common physiological response to obesity 197:238 A common physiological response to obesity is hypertension, which induces cardiac remodeling and hypertrophy. 24523346 2 77 theme physiological 206:218 arg1 hypertension 243:254 hypertension 243:254 hypertension 243:254 A common physiological response to obesity is hypertension, which induces cardiac remodeling and hypertrophy. 24523346 11 78 theme Western 1558:1564 arg1 analysis 1571:1578 Western blot analysis 1558:1578 Western blot analysis 1558:1578 Western blot analysis showed that HDAC protein levels were not different between groups; however, relative to controls, Western diet hearts showed increased REST and decreased ANP and skeletal α-actin. 24523346 3 79 theme gene 500:503 arg1 program 505:511 a fetal cardiac gene program 484:511 a fetal cardiac gene program 484:511 Hypertrophy is regulated at the level of chromatin by repressor element 1-silencing transcription factor (REST), and pathological hypertrophy is associated with reexpression of a fetal cardiac gene program. 24523346 11 80 theme diet 1686:1689 arg1 hearts 1691:1696 Western diet hearts 1678:1696 Western diet hearts 1678:1696 Western blot analysis showed that HDAC protein levels were not different between groups; however, relative to controls, Western diet hearts showed increased REST and decreased ANP and skeletal α-actin. 27590087 1 0 with reagents 287:294 arg1 triphenylphosphine 331:348 triphenylphosphine 331:348 triphenylphosphine (TPP) 331:354 We have developed three kinds of novel derivatization reagents (4-CEBTPP, 4-CBBTPP, 5-COTPP) with triphenylphosphine (TPP) as a basic structure carrying a permanent positive charge for resolution of the oligosaccharides in glycoprotein using high-performance liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). 27590087 1 0 with reagents 287:294 arg1 TPP 351:353 TPP 351:353 TPP 351:353 We have developed three kinds of novel derivatization reagents (4-CEBTPP, 4-CBBTPP, 5-COTPP) with triphenylphosphine (TPP) as a basic structure carrying a permanent positive charge for resolution of the oligosaccharides in glycoprotein using high-performance liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). 27590087 3 1 theme reaction 783:790 arg1 mode 809:812 the selected reaction monitoring (SRM) mode 770:812 the selected reaction monitoring (SRM) mode 770:812 The final derivatives were analyzed by ESI-MS and sensitively detected in the selected reaction monitoring (SRM) mode. 27590087 1 2 theme liquid 492:497 arg1 chromatography 499:512 high-performance liquid chromatography 475:512 high-performance liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) 475:576 We have developed three kinds of novel derivatization reagents (4-CEBTPP, 4-CBBTPP, 5-COTPP) with triphenylphosphine (TPP) as a basic structure carrying a permanent positive charge for resolution of the oligosaccharides in glycoprotein using high-performance liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). 27590087 9 3 theme selected-ion 1670:1681 arg1 chromatogram 1683:1694 the selected-ion chromatogram 1666:1694 the selected-ion chromatogram 1666:1694 4-CEBTPP-SGA was easily identified by the selected-ion chromatogram in the product ion scan (m/z 120.09) and in the precursor ion scan (m/z 627.37) by MS/MS detection. 27590087 6 4 theme conventional 1285:1296 arg1 Fmoc-Cl 1320:1326 Fmoc-Cl 1320:1326 Fmoc-Cl 1320:1326 Among the reagents, the positively charged 4-CEBTPP derivative's peak area was the highest; 4-CEBTPP with a positively charged structure showed about a 20 times greater sensitivity for the glycosylamine of the SGP product compared to the conventional fluorescence reagent, Fmoc-Cl. 27590087 6 4 theme conventional 1285:1296 arg1 reagent 1311:1317 the conventional fluorescence reagent 1281:1317 the conventional fluorescence reagent 1281:1317 Among the reagents, the positively charged 4-CEBTPP derivative's peak area was the highest; 4-CEBTPP with a positively charged structure showed about a 20 times greater sensitivity for the glycosylamine of the SGP product compared to the conventional fluorescence reagent, Fmoc-Cl. 27590087 1 5 theme electrospray 514:525 arg1 LC-ESI-MS/MS 564:575 LC-ESI-MS/MS 564:575 LC-ESI-MS/MS 564:575 We have developed three kinds of novel derivatization reagents (4-CEBTPP, 4-CBBTPP, 5-COTPP) with triphenylphosphine (TPP) as a basic structure carrying a permanent positive charge for resolution of the oligosaccharides in glycoprotein using high-performance liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). 27590087 1 5 theme electrospray 514:525 arg1 spectrometry 550:561 high-performance liquid chromatography electrospray ionization tandem mass spectrometry 475:561 high-performance liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) 475:576 We have developed three kinds of novel derivatization reagents (4-CEBTPP, 4-CBBTPP, 5-COTPP) with triphenylphosphine (TPP) as a basic structure carrying a permanent positive charge for resolution of the oligosaccharides in glycoprotein using high-performance liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). 27590087 10 6 theme electrospray 1908:1919 arg1 ionization 1921:1930 the electrospray ionization 1904:1930 the electrospray ionization 1904:1930 The derivatized analytes have a high ionization efficiency and they are detected with a high sensitivity in the electrospray ionization. 27590087 1 7 theme tandem 538:543 arg1 LC-ESI-MS/MS 564:575 LC-ESI-MS/MS 564:575 LC-ESI-MS/MS 564:575 We have developed three kinds of novel derivatization reagents (4-CEBTPP, 4-CBBTPP, 5-COTPP) with triphenylphosphine (TPP) as a basic structure carrying a permanent positive charge for resolution of the oligosaccharides in glycoprotein using high-performance liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). 27590087 1 7 theme tandem 538:543 arg1 spectrometry 550:561 high-performance liquid chromatography electrospray ionization tandem mass spectrometry 475:561 high-performance liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) 475:576 We have developed three kinds of novel derivatization reagents (4-CEBTPP, 4-CBBTPP, 5-COTPP) with triphenylphosphine (TPP) as a basic structure carrying a permanent positive charge for resolution of the oligosaccharides in glycoprotein using high-performance liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). 27590087 11 8 theme higher 1999:2004 arg1 sensitivity 2006:2016 a higher sensitivity 1997:2016 a higher sensitivity for the oligosaccharide analysis 1997:2049 The novel derivatization reagent with a multi-function provided a higher sensitivity for the oligosaccharide analysis, as well as a better specificity and feasibility. 27590087 9 9 theme product 1703:1709 arg1 m/z 1721:1723 m/z 120.09 1721:1730 m/z 120.09 1721:1730 4-CEBTPP-SGA was easily identified by the selected-ion chromatogram in the product ion scan (m/z 120.09) and in the precursor ion scan (m/z 627.37) by MS/MS detection. 27590087 9 9 theme product 1703:1709 arg1 ion 1711:1713 the product ion scan 1699:1718 the product ion scan (m/z 120.09) 1699:1731 4-CEBTPP-SGA was easily identified by the selected-ion chromatogram in the product ion scan (m/z 120.09) and in the precursor ion scan (m/z 627.37) by MS/MS detection. 27590087 6 10 dep showed 1184:1189 arg1 compared 1269:1276 compared 1269:1276 showed about a 20 times greater sensitivity for the glycosylamine of the SGP product compared to the conventional fluorescence reagent, Fmoc-Cl 1184:1326 Among the reagents, the positively charged 4-CEBTPP derivative's peak area was the highest; 4-CEBTPP with a positively charged structure showed about a 20 times greater sensitivity for the glycosylamine of the SGP product compared to the conventional fluorescence reagent, Fmoc-Cl. 27590087 10 11 theme high 1884:1887 arg1 sensitivity 1889:1899 a high sensitivity 1882:1899 a high sensitivity in the electrospray ionization 1882:1930 The derivatized analytes have a high ionization efficiency and they are detected with a high sensitivity in the electrospray ionization. 27590087 6 12 theme product 1261:1267 arg1 glycosylamine 1236:1248 the glycosylamine 1232:1248 the glycosylamine of the SGP product 1232:1267 Among the reagents, the positively charged 4-CEBTPP derivative's peak area was the highest; 4-CEBTPP with a positively charged structure showed about a 20 times greater sensitivity for the glycosylamine of the SGP product compared to the conventional fluorescence reagent, Fmoc-Cl. 27590087 11 13 theme novel 1937:1941 arg1 reagent 1958:1964 The novel derivatization reagent 1933:1964 The novel derivatization reagent with a multi-function 1933:1986 The novel derivatization reagent with a multi-function provided a higher sensitivity for the oligosaccharide analysis, as well as a better specificity and feasibility. 27590087 6 14 theme charged 1166:1172 arg1 structure 1174:1182 a positively charged structure 1153:1182 a positively charged structure 1153:1182 Among the reagents, the positively charged 4-CEBTPP derivative's peak area was the highest; 4-CEBTPP with a positively charged structure showed about a 20 times greater sensitivity for the glycosylamine of the SGP product compared to the conventional fluorescence reagent, Fmoc-Cl. 27590087 0 15 theme high-performance 144:159 arg1 chromatography 168:181 high-performance liquid chromatography electrospray ionization tandem mass spectrometry 144:230 high-performance liquid chromatography electrospray ionization tandem mass spectrometry 144:230 Highly sensitive derivatization reagents possessing positively charged structures for the determination of oligosaccharides in glycoproteins by high-performance liquid chromatography electrospray ionization tandem mass spectrometry. 27590087 11 16 theme oligosaccharide 2026:2040 arg1 analysis 2042:2049 the oligosaccharide analysis 2022:2049 the oligosaccharide analysis 2022:2049 The novel derivatization reagent with a multi-function provided a higher sensitivity for the oligosaccharide analysis, as well as a better specificity and feasibility. 27590087 0 17 from determination 90:102 arg1 glycoproteins 127:139 glycoproteins 127:139 glycoproteins 127:139 Highly sensitive derivatization reagents possessing positively charged structures for the determination of oligosaccharides in glycoproteins by high-performance liquid chromatography electrospray ionization tandem mass spectrometry. 27590087 6 18 theme SGP 1257:1259 arg1 product 1261:1267 the SGP product 1253:1267 the SGP product 1253:1267 Among the reagents, the positively charged 4-CEBTPP derivative's peak area was the highest; 4-CEBTPP with a positively charged structure showed about a 20 times greater sensitivity for the glycosylamine of the SGP product compared to the conventional fluorescence reagent, Fmoc-Cl. 27590087 7 19 theme various 1342:1348 arg1 ions 1359:1362 various fragment ions 1342:1362 various fragment ions based on the carbohydrate units 1342:1394 In addition, various fragment ions based on the carbohydrate units also appeared in the MS/MS spectra. 27590087 6 20 dep times 1202:1206 arg1 greater 1208:1214 greater 1208:1214 greater 1208:1214 Among the reagents, the positively charged 4-CEBTPP derivative's peak area was the highest; 4-CEBTPP with a positively charged structure showed about a 20 times greater sensitivity for the glycosylamine of the SGP product compared to the conventional fluorescence reagent, Fmoc-Cl. 27590087 9 21 dep ion 1754:1756 arg1 scan 1758:1761 scan 1758:1761 scan 1758:1761 4-CEBTPP-SGA was easily identified by the selected-ion chromatogram in the product ion scan (m/z 120.09) and in the precursor ion scan (m/z 627.37) by MS/MS detection. 27590087 1 22 theme novel 266:270 arg1 reagents 287:294 novel derivatization reagents 266:294 novel derivatization reagents (4-CEBTPP, 4-CBBTPP, 5-COTPP) with triphenylphosphine (TPP) 266:354 We have developed three kinds of novel derivatization reagents (4-CEBTPP, 4-CBBTPP, 5-COTPP) with triphenylphosphine (TPP) as a basic structure carrying a permanent positive charge for resolution of the oligosaccharides in glycoprotein using high-performance liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). 27590087 1 23 dep reagents 287:294 arg1 4-CBBTPP 307:314 4-CBBTPP 307:314 4-CBBTPP 307:314 We have developed three kinds of novel derivatization reagents (4-CEBTPP, 4-CBBTPP, 5-COTPP) with triphenylphosphine (TPP) as a basic structure carrying a permanent positive charge for resolution of the oligosaccharides in glycoprotein using high-performance liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). 27590087 1 23 dep reagents 287:294 arg1 4-CEBTPP 297:304 4-CEBTPP 297:304 4-CEBTPP 297:304 We have developed three kinds of novel derivatization reagents (4-CEBTPP, 4-CBBTPP, 5-COTPP) with triphenylphosphine (TPP) as a basic structure carrying a permanent positive charge for resolution of the oligosaccharides in glycoprotein using high-performance liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). 27590087 1 23 dep reagents 287:294 arg1 5-COTPP 317:323 5-COTPP 317:323 5-COTPP 317:323 We have developed three kinds of novel derivatization reagents (4-CEBTPP, 4-CBBTPP, 5-COTPP) with triphenylphosphine (TPP) as a basic structure carrying a permanent positive charge for resolution of the oligosaccharides in glycoprotein using high-performance liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). 27590087 6 24 dep sensitivity 1216:1226 arg1 times 1202:1206 times 1202:1206 times 1202:1206 Among the reagents, the positively charged 4-CEBTPP derivative's peak area was the highest; 4-CEBTPP with a positively charged structure showed about a 20 times greater sensitivity for the glycosylamine of the SGP product compared to the conventional fluorescence reagent, Fmoc-Cl. 27590087 0 25 theme ionization 196:205 arg1 spectrometry 219:230 electrospray ionization tandem mass spectrometry 183:230 high-performance liquid chromatography electrospray ionization tandem mass spectrometry 144:230 Highly sensitive derivatization reagents possessing positively charged structures for the determination of oligosaccharides in glycoproteins by high-performance liquid chromatography electrospray ionization tandem mass spectrometry. 27590087 5 26 used used 932:935 arg2 we 929:930 we 929:930 we 929:930 Therefore, we used the limit of detection of the reagent products detected by the SRM and evaluated the utility of each reagent. 27590087 0 27 from glycoproteins 127:139 arg1 determination 90:102 the determination 86:102 the determination of oligosaccharides in glycoproteins by high-performance liquid chromatography electrospray ionization tandem mass spectrometry 86:230 Highly sensitive derivatization reagents possessing positively charged structures for the determination of oligosaccharides in glycoproteins by high-performance liquid chromatography electrospray ionization tandem mass spectrometry. 27590087 0 28 theme mass 214:217 arg1 spectrometry 219:230 electrospray ionization tandem mass spectrometry 183:230 high-performance liquid chromatography electrospray ionization tandem mass spectrometry 144:230 Highly sensitive derivatization reagents possessing positively charged structures for the determination of oligosaccharides in glycoproteins by high-performance liquid chromatography electrospray ionization tandem mass spectrometry. 27590087 5 29 theme reagent 967:973 arg1 products 975:982 the reagent products 963:982 the reagent products detected by the SRM 963:1002 Therefore, we used the limit of detection of the reagent products detected by the SRM and evaluated the utility of each reagent. 27590087 9 30 theme precursor 1744:1752 arg1 ion 1754:1756 the precursor ion scan 1740:1761 the precursor ion scan (m/z 627.37) 1740:1774 4-CEBTPP-SGA was easily identified by the selected-ion chromatogram in the product ion scan (m/z 120.09) and in the precursor ion scan (m/z 627.37) by MS/MS detection. 27590087 9 30 theme precursor 1744:1752 arg1 m/z 1764:1766 m/z 627.37 1764:1773 m/z 627.37 1764:1773 4-CEBTPP-SGA was easily identified by the selected-ion chromatogram in the product ion scan (m/z 120.09) and in the precursor ion scan (m/z 627.37) by MS/MS detection. 27590087 0 31 from oligosaccharides 107:122 arg1 glycoproteins 127:139 glycoproteins 127:139 glycoproteins 127:139 Highly sensitive derivatization reagents possessing positively charged structures for the determination of oligosaccharides in glycoproteins by high-performance liquid chromatography electrospray ionization tandem mass spectrometry. 27590087 1 32 theme basic 361:365 arg1 kinds 257:261 three kinds 251:261 three kinds of novel derivatization reagents (4-CEBTPP, 4-CBBTPP, 5-COTPP) with triphenylphosphine (TPP) 251:354 We have developed three kinds of novel derivatization reagents (4-CEBTPP, 4-CBBTPP, 5-COTPP) with triphenylphosphine (TPP) as a basic structure carrying a permanent positive charge for resolution of the oligosaccharides in glycoprotein using high-performance liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). 27590087 1 32 theme basic 361:365 arg1 structure 367:375 a basic structure 359:375 a basic structure carrying a permanent positive charge for resolution of the oligosaccharides in glycoprotein using high-performance liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) 359:576 We have developed three kinds of novel derivatization reagents (4-CEBTPP, 4-CBBTPP, 5-COTPP) with triphenylphosphine (TPP) as a basic structure carrying a permanent positive charge for resolution of the oligosaccharides in glycoprotein using high-performance liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). 27590087 10 33 theme derivatized 1800:1810 arg1 analytes 1812:1819 The derivatized analytes 1796:1819 The derivatized analytes 1796:1819 The derivatized analytes have a high ionization efficiency and they are detected with a high sensitivity in the electrospray ionization. 27590087 0 34 dep chromatography 168:181 arg1 spectrometry 219:230 electrospray ionization tandem mass spectrometry 183:230 high-performance liquid chromatography electrospray ionization tandem mass spectrometry 144:230 Highly sensitive derivatization reagents possessing positively charged structures for the determination of oligosaccharides in glycoproteins by high-performance liquid chromatography electrospray ionization tandem mass spectrometry. 27590087 1 35 from glycoprotein 456:467 arg1 resolution 418:427 resolution 418:427 resolution of the oligosaccharides in glycoprotein using high-performance liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) 418:576 We have developed three kinds of novel derivatization reagents (4-CEBTPP, 4-CBBTPP, 5-COTPP) with triphenylphosphine (TPP) as a basic structure carrying a permanent positive charge for resolution of the oligosaccharides in glycoprotein using high-performance liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). 27590087 0 36 theme oligosaccharides 107:122 arg1 determination 90:102 the determination 86:102 the determination of oligosaccharides in glycoproteins by high-performance liquid chromatography electrospray ionization tandem mass spectrometry 86:230 Highly sensitive derivatization reagents possessing positively charged structures for the determination of oligosaccharides in glycoproteins by high-performance liquid chromatography electrospray ionization tandem mass spectrometry. 27590087 1 37 theme permanent 388:396 arg1 charge 407:412 a permanent positive charge 386:412 a permanent positive charge for resolution of the oligosaccharides in glycoprotein using high-performance liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) 386:576 We have developed three kinds of novel derivatization reagents (4-CEBTPP, 4-CBBTPP, 5-COTPP) with triphenylphosphine (TPP) as a basic structure carrying a permanent positive charge for resolution of the oligosaccharides in glycoprotein using high-performance liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). 27590087 12 38 theme proposed 2204:2211 arg1 procedure 2213:2221 the proposed procedure 2200:2221 the proposed procedure 2200:2221 Furthermore, several oligosaccharides in fetuin and ribonuclease B were successfully identified by the proposed procedure. 27590087 11 39 with reagent 1958:1964 arg1 multi-function 1973:1986 a multi-function 1971:1986 a multi-function 1971:1986 The novel derivatization reagent with a multi-function provided a higher sensitivity for the oligosaccharide analysis, as well as a better specificity and feasibility. 27590087 9 40 theme MS/MS 1779:1783 arg1 detection 1785:1793 MS/MS detection 1779:1793 MS/MS detection 1779:1793 4-CEBTPP-SGA was easily identified by the selected-ion chromatogram in the product ion scan (m/z 120.09) and in the precursor ion scan (m/z 627.37) by MS/MS detection. 27590087 6 41 theme 4-CEBTPP 1090:1097 arg1 derivative 1099:1108 the positively charged 4-CEBTPP derivative 1067:1108 the positively charged 4-CEBTPP derivative's peak area 1067:1120 Among the reagents, the positively charged 4-CEBTPP derivative's peak area was the highest; 4-CEBTPP with a positively charged structure showed about a 20 times greater sensitivity for the glycosylamine of the SGP product compared to the conventional fluorescence reagent, Fmoc-Cl. 27590087 0 42 theme derivatization 17:30 arg1 reagents 32:39 Highly sensitive derivatization reagents 0:39 Highly sensitive derivatization reagents 0:39 Highly sensitive derivatization reagents possessing positively charged structures for the determination of oligosaccharides in glycoproteins by high-performance liquid chromatography electrospray ionization tandem mass spectrometry. 27590087 9 43 dep ion 1711:1713 arg1 scan 1715:1718 scan 1715:1718 scan 1715:1718 4-CEBTPP-SGA was easily identified by the selected-ion chromatogram in the product ion scan (m/z 120.09) and in the precursor ion scan (m/z 627.37) by MS/MS detection. 27590087 10 44 contain have 1821:1824 arg1 analytes 1812:1819 The derivatized analytes 1796:1819 The derivatized analytes 1796:1819 The derivatized analytes have a high ionization efficiency and they are detected with a high sensitivity in the electrospray ionization. 27590087 10 44 contain have 1821:1824 arg2 efficiency 1844:1853 a high ionization efficiency 1826:1853 a high ionization efficiency 1826:1853 The derivatized analytes have a high ionization efficiency and they are detected with a high sensitivity in the electrospray ionization. 27590087 10 45 theme high 1828:1831 arg1 efficiency 1844:1853 a high ionization efficiency 1826:1853 a high ionization efficiency 1826:1853 The derivatized analytes have a high ionization efficiency and they are detected with a high sensitivity in the electrospray ionization. 27590087 4 46 theme fmol 897:900 arg1 30fmol 909:914 30fmol 909:914 30fmol 909:914 Furthermore, the limits of detection (S/N=3) on the SRM chromatograms were at the fmol level (30fmol). 27590087 4 46 theme fmol 897:900 arg1 level 902:906 the fmol level 893:906 the fmol level (30fmol) 893:915 Furthermore, the limits of detection (S/N=3) on the SRM chromatograms were at the fmol level (30fmol). 27590087 0 47 theme charged 63:69 arg1 structures 71:80 positively charged structures 52:80 positively charged structures 52:80 Highly sensitive derivatization reagents possessing positively charged structures for the determination of oligosaccharides in glycoproteins by high-performance liquid chromatography electrospray ionization tandem mass spectrometry. 27590087 3 48 theme selected 774:781 arg1 mode 809:812 the selected reaction monitoring (SRM) mode 770:812 the selected reaction monitoring (SRM) mode 770:812 The final derivatives were analyzed by ESI-MS and sensitively detected in the selected reaction monitoring (SRM) mode. 27590087 1 49 theme derivatization 272:285 arg1 reagents 287:294 novel derivatization reagents 266:294 novel derivatization reagents (4-CEBTPP, 4-CBBTPP, 5-COTPP) with triphenylphosphine (TPP) 266:354 We have developed three kinds of novel derivatization reagents (4-CEBTPP, 4-CBBTPP, 5-COTPP) with triphenylphosphine (TPP) as a basic structure carrying a permanent positive charge for resolution of the oligosaccharides in glycoprotein using high-performance liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). 27590087 6 50 with 4-CEBTPP 1139:1146 arg1 structure 1174:1182 a positively charged structure 1153:1182 a positively charged structure 1153:1182 Among the reagents, the positively charged 4-CEBTPP derivative's peak area was the highest; 4-CEBTPP with a positively charged structure showed about a 20 times greater sensitivity for the glycosylamine of the SGP product compared to the conventional fluorescence reagent, Fmoc-Cl. 27590087 5 51 theme reagent 1038:1044 arg1 utility 1022:1028 the utility 1018:1028 the utility of each reagent 1018:1044 Therefore, we used the limit of detection of the reagent products detected by the SRM and evaluated the utility of each reagent. 27590087 3 52 theme SRM 804:806 arg1 mode 809:812 the selected reaction monitoring (SRM) mode 770:812 the selected reaction monitoring (SRM) mode 770:812 The final derivatives were analyzed by ESI-MS and sensitively detected in the selected reaction monitoring (SRM) mode. 27590087 11 53 dep better 2065:2070 arg1 specificity 2072:2082 specificity 2072:2082 specificity 2072:2082 The novel derivatization reagent with a multi-function provided a higher sensitivity for the oligosaccharide analysis, as well as a better specificity and feasibility. 27590087 11 53 dep better 2065:2070 arg1 a 2063:2063 a 2063:2063 a 2063:2063 The novel derivatization reagent with a multi-function provided a higher sensitivity for the oligosaccharide analysis, as well as a better specificity and feasibility. 27590087 3 54 theme monitoring 792:801 arg1 mode 809:812 the selected reaction monitoring (SRM) mode 770:812 the selected reaction monitoring (SRM) mode 770:812 The final derivatives were analyzed by ESI-MS and sensitively detected in the selected reaction monitoring (SRM) mode. 27590087 6 55 theme fluorescence 1298:1309 arg1 Fmoc-Cl 1320:1326 Fmoc-Cl 1320:1326 Fmoc-Cl 1320:1326 Among the reagents, the positively charged 4-CEBTPP derivative's peak area was the highest; 4-CEBTPP with a positively charged structure showed about a 20 times greater sensitivity for the glycosylamine of the SGP product compared to the conventional fluorescence reagent, Fmoc-Cl. 27590087 6 55 theme fluorescence 1298:1309 arg1 reagent 1311:1317 the conventional fluorescence reagent 1281:1317 the conventional fluorescence reagent 1281:1317 Among the reagents, the positively charged 4-CEBTPP derivative's peak area was the highest; 4-CEBTPP with a positively charged structure showed about a 20 times greater sensitivity for the glycosylamine of the SGP product compared to the conventional fluorescence reagent, Fmoc-Cl. 27590087 1 56 theme chromatography 499:512 arg1 LC-ESI-MS/MS 564:575 LC-ESI-MS/MS 564:575 LC-ESI-MS/MS 564:575 We have developed three kinds of novel derivatization reagents (4-CEBTPP, 4-CBBTPP, 5-COTPP) with triphenylphosphine (TPP) as a basic structure carrying a permanent positive charge for resolution of the oligosaccharides in glycoprotein using high-performance liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). 27590087 1 56 theme chromatography 499:512 arg1 spectrometry 550:561 high-performance liquid chromatography electrospray ionization tandem mass spectrometry 475:561 high-performance liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) 475:576 We have developed three kinds of novel derivatization reagents (4-CEBTPP, 4-CBBTPP, 5-COTPP) with triphenylphosphine (TPP) as a basic structure carrying a permanent positive charge for resolution of the oligosaccharides in glycoprotein using high-performance liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). 27590087 2 57 theme PNGase 686:691 arg1 F 693:693 PNGase F 686:693 PNGase F 686:693 The synthesized reagents reacted with the sialylglycosylamine of the sialylglycopeptide after treatment by PNGase F. 27590087 6 58 theme 20 1199:1200 arg1 times 1202:1206 times 1202:1206 times 1202:1206 Among the reagents, the positively charged 4-CEBTPP derivative's peak area was the highest; 4-CEBTPP with a positively charged structure showed about a 20 times greater sensitivity for the glycosylamine of the SGP product compared to the conventional fluorescence reagent, Fmoc-Cl. 27590087 1 59 theme ionization 527:536 arg1 LC-ESI-MS/MS 564:575 LC-ESI-MS/MS 564:575 LC-ESI-MS/MS 564:575 We have developed three kinds of novel derivatization reagents (4-CEBTPP, 4-CBBTPP, 5-COTPP) with triphenylphosphine (TPP) as a basic structure carrying a permanent positive charge for resolution of the oligosaccharides in glycoprotein using high-performance liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). 27590087 1 59 theme ionization 527:536 arg1 spectrometry 550:561 high-performance liquid chromatography electrospray ionization tandem mass spectrometry 475:561 high-performance liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) 475:576 We have developed three kinds of novel derivatization reagents (4-CEBTPP, 4-CBBTPP, 5-COTPP) with triphenylphosphine (TPP) as a basic structure carrying a permanent positive charge for resolution of the oligosaccharides in glycoprotein using high-performance liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). 27590087 1 60 theme mass 545:548 arg1 LC-ESI-MS/MS 564:575 LC-ESI-MS/MS 564:575 LC-ESI-MS/MS 564:575 We have developed three kinds of novel derivatization reagents (4-CEBTPP, 4-CBBTPP, 5-COTPP) with triphenylphosphine (TPP) as a basic structure carrying a permanent positive charge for resolution of the oligosaccharides in glycoprotein using high-performance liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). 27590087 1 60 theme mass 545:548 arg1 spectrometry 550:561 high-performance liquid chromatography electrospray ionization tandem mass spectrometry 475:561 high-performance liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) 475:576 We have developed three kinds of novel derivatization reagents (4-CEBTPP, 4-CBBTPP, 5-COTPP) with triphenylphosphine (TPP) as a basic structure carrying a permanent positive charge for resolution of the oligosaccharides in glycoprotein using high-performance liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). 27590087 0 61 theme liquid 161:166 arg1 chromatography 168:181 high-performance liquid chromatography electrospray ionization tandem mass spectrometry 144:230 high-performance liquid chromatography electrospray ionization tandem mass spectrometry 144:230 Highly sensitive derivatization reagents possessing positively charged structures for the determination of oligosaccharides in glycoproteins by high-performance liquid chromatography electrospray ionization tandem mass spectrometry. 27590087 10 62 from sensitivity 1889:1899 arg1 ionization 1921:1930 the electrospray ionization 1904:1930 the electrospray ionization 1904:1930 The derivatized analytes have a high ionization efficiency and they are detected with a high sensitivity in the electrospray ionization. 27590087 7 63 theme MS/MS 1417:1421 arg1 spectra 1423:1429 the MS/MS spectra 1413:1429 the MS/MS spectra 1413:1429 In addition, various fragment ions based on the carbohydrate units also appeared in the MS/MS spectra. 27590087 0 64 theme electrospray 183:194 arg1 spectrometry 219:230 electrospray ionization tandem mass spectrometry 183:230 high-performance liquid chromatography electrospray ionization tandem mass spectrometry 144:230 Highly sensitive derivatization reagents possessing positively charged structures for the determination of oligosaccharides in glycoproteins by high-performance liquid chromatography electrospray ionization tandem mass spectrometry. 27590087 11 65 theme derivatization 1943:1956 arg1 reagent 1958:1964 The novel derivatization reagent 1933:1964 The novel derivatization reagent with a multi-function 1933:1986 The novel derivatization reagent with a multi-function provided a higher sensitivity for the oligosaccharide analysis, as well as a better specificity and feasibility. 27590087 0 66 theme tandem 207:212 arg1 spectrometry 219:230 electrospray ionization tandem mass spectrometry 183:230 high-performance liquid chromatography electrospray ionization tandem mass spectrometry 144:230 Highly sensitive derivatization reagents possessing positively charged structures for the determination of oligosaccharides in glycoproteins by high-performance liquid chromatography electrospray ionization tandem mass spectrometry. 27590087 1 67 theme oligosaccharides 436:451 arg1 resolution 418:427 resolution 418:427 resolution of the oligosaccharides in glycoprotein using high-performance liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) 418:576 We have developed three kinds of novel derivatization reagents (4-CEBTPP, 4-CBBTPP, 5-COTPP) with triphenylphosphine (TPP) as a basic structure carrying a permanent positive charge for resolution of the oligosaccharides in glycoprotein using high-performance liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). 27590087 5 68 theme detection 950:958 arg1 limit 941:945 the limit 937:945 the limit of detection of the reagent products detected by the SRM 937:1002 Therefore, we used the limit of detection of the reagent products detected by the SRM and evaluated the utility of each reagent. 27590087 2 69 gly sialylglycopeptide 648:665 arg2 sialylglycopeptide 648:665 the sialylglycopeptide 644:665 the sialylglycopeptide 644:665 The synthesized reagents reacted with the sialylglycosylamine of the sialylglycopeptide after treatment by PNGase F. 27590087 2 70 theme sialylglycopeptide 648:665 arg1 sialylglycosylamine 621:639 the sialylglycosylamine 617:639 the sialylglycosylamine of the sialylglycopeptide after treatment by PNGase F 617:693 The synthesized reagents reacted with the sialylglycosylamine of the sialylglycopeptide after treatment by PNGase F. 27590087 7 71 theme carbohydrate 1377:1388 arg1 units 1390:1394 the carbohydrate units 1373:1394 the carbohydrate units 1373:1394 In addition, various fragment ions based on the carbohydrate units also appeared in the MS/MS spectra. 27590087 1 72 theme high-performance 475:490 arg1 chromatography 499:512 high-performance liquid chromatography 475:512 high-performance liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) 475:576 We have developed three kinds of novel derivatization reagents (4-CEBTPP, 4-CBBTPP, 5-COTPP) with triphenylphosphine (TPP) as a basic structure carrying a permanent positive charge for resolution of the oligosaccharides in glycoprotein using high-performance liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). 27590087 3 73 theme final 700:704 arg1 derivatives 706:716 The final derivatives 696:716 The final derivatives 696:716 The final derivatives were analyzed by ESI-MS and sensitively detected in the selected reaction monitoring (SRM) mode. 27590087 1 74 from oligosaccharides 436:451 arg1 glycoprotein 456:467 glycoprotein 456:467 glycoprotein using high-performance liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) 456:576 We have developed three kinds of novel derivatization reagents (4-CEBTPP, 4-CBBTPP, 5-COTPP) with triphenylphosphine (TPP) as a basic structure carrying a permanent positive charge for resolution of the oligosaccharides in glycoprotein using high-performance liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). 27590087 4 75 theme detection 842:850 arg1 limits 832:837 the limits 828:837 the limits of detection (S/N=3) on the SRM chromatograms 828:883 Furthermore, the limits of detection (S/N=3) on the SRM chromatograms were at the fmol level (30fmol). 27590087 1 76 from resolution 418:427 arg1 glycoprotein 456:467 glycoprotein 456:467 glycoprotein using high-performance liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) 456:576 We have developed three kinds of novel derivatization reagents (4-CEBTPP, 4-CBBTPP, 5-COTPP) with triphenylphosphine (TPP) as a basic structure carrying a permanent positive charge for resolution of the oligosaccharides in glycoprotein using high-performance liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). 27590087 1 77 theme positive 398:405 arg1 charge 407:412 a permanent positive charge 386:412 a permanent positive charge for resolution of the oligosaccharides in glycoprotein using high-performance liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) 386:576 We have developed three kinds of novel derivatization reagents (4-CEBTPP, 4-CBBTPP, 5-COTPP) with triphenylphosphine (TPP) as a basic structure carrying a permanent positive charge for resolution of the oligosaccharides in glycoprotein using high-performance liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). 27590087 12 78 from oligosaccharides 2122:2137 arg1 fetuin 2142:2147 fetuin 2142:2147 fetuin 2142:2147 Furthermore, several oligosaccharides in fetuin and ribonuclease B were successfully identified by the proposed procedure. 27590087 12 78 from oligosaccharides 2122:2137 arg1 B 2166:2166 ribonuclease B 2153:2166 ribonuclease B 2153:2166 Furthermore, several oligosaccharides in fetuin and ribonuclease B were successfully identified by the proposed procedure. 27590087 6 79 theme peak 1112:1115 arg1 area 1117:1120 the positively charged 4-CEBTPP derivative's peak area 1067:1120 the positively charged 4-CEBTPP derivative's peak area 1067:1120 Among the reagents, the positively charged 4-CEBTPP derivative's peak area was the highest; 4-CEBTPP with a positively charged structure showed about a 20 times greater sensitivity for the glycosylamine of the SGP product compared to the conventional fluorescence reagent, Fmoc-Cl. 27590087 6 79 theme peak 1112:1115 arg1 highest 1130:1136 highest 1130:1136 highest 1130:1136 Among the reagents, the positively charged 4-CEBTPP derivative's peak area was the highest; 4-CEBTPP with a positively charged structure showed about a 20 times greater sensitivity for the glycosylamine of the SGP product compared to the conventional fluorescence reagent, Fmoc-Cl. 27590087 2 80 theme synthesized 583:593 arg1 reagents 595:602 The synthesized reagents 579:602 The synthesized reagents 579:602 The synthesized reagents reacted with the sialylglycosylamine of the sialylglycopeptide after treatment by PNGase F. 27590087 0 81 theme sensitive 7:15 arg1 reagents 32:39 Highly sensitive derivatization reagents 0:39 Highly sensitive derivatization reagents 0:39 Highly sensitive derivatization reagents possessing positively charged structures for the determination of oligosaccharides in glycoproteins by high-performance liquid chromatography electrospray ionization tandem mass spectrometry. 27590087 4 82 from limits 832:837 arg1 chromatograms 871:883 the SRM chromatograms 863:883 the SRM chromatograms 863:883 Furthermore, the limits of detection (S/N=3) on the SRM chromatograms were at the fmol level (30fmol). 27590087 5 83 theme products 975:982 arg1 detection 950:958 detection 950:958 detection of the reagent products detected by the SRM 950:1002 Therefore, we used the limit of detection of the reagent products detected by the SRM and evaluated the utility of each reagent. 27590087 0 84 gly glycoproteins 127:139 arg1 glycoproteins 127:139 glycoproteins 127:139 glycoproteins 127:139 Highly sensitive derivatization reagents possessing positively charged structures for the determination of oligosaccharides in glycoproteins by high-performance liquid chromatography electrospray ionization tandem mass spectrometry. 27590087 6 85 theme charged 1082:1088 arg1 derivative 1099:1108 the positively charged 4-CEBTPP derivative 1067:1108 the positively charged 4-CEBTPP derivative's peak area 1067:1120 Among the reagents, the positively charged 4-CEBTPP derivative's peak area was the highest; 4-CEBTPP with a positively charged structure showed about a 20 times greater sensitivity for the glycosylamine of the SGP product compared to the conventional fluorescence reagent, Fmoc-Cl. 27590087 12 86 theme several 2114:2120 arg1 oligosaccharides 2122:2137 several oligosaccharides 2114:2137 several oligosaccharides in fetuin and ribonuclease B 2114:2166 Furthermore, several oligosaccharides in fetuin and ribonuclease B were successfully identified by the proposed procedure. 27590087 7 87 theme fragment 1350:1357 arg1 ions 1359:1362 various fragment ions 1342:1362 various fragment ions based on the carbohydrate units 1342:1394 In addition, various fragment ions based on the carbohydrate units also appeared in the MS/MS spectra. 27590087 8 88 theme important 1576:1584 arg1 m/z 1515:1517 m/z 120.09 1515:1524 m/z 120.09 (CE=100eV) corresponding to 4-CEBTPP 1515:1561 Among the fragment ions, m/z 627.37 (CE=40eV) corresponding to 4-CEBTPP-GlcNAc and m/z 120.09 (CE=100eV) corresponding to 4-CEBTPP are the most important ones for identifying the oligosaccharide. 27590087 8 88 theme important 1576:1584 arg1 ones 1586:1589 the most important ones 1567:1589 the most important ones for identifying the oligosaccharide 1567:1625 Among the fragment ions, m/z 627.37 (CE=40eV) corresponding to 4-CEBTPP-GlcNAc and m/z 120.09 (CE=100eV) corresponding to 4-CEBTPP are the most important ones for identifying the oligosaccharide. 27590087 8 88 theme important 1576:1584 arg1 m/z 1457:1459 m/z 627.37 1457:1466 m/z 627.37 (CE=40eV) corresponding to 4-CEBTPP-GlcNAc 1457:1509 Among the fragment ions, m/z 627.37 (CE=40eV) corresponding to 4-CEBTPP-GlcNAc and m/z 120.09 (CE=100eV) corresponding to 4-CEBTPP are the most important ones for identifying the oligosaccharide. 27590087 10 89 theme ionization 1833:1842 arg1 efficiency 1844:1853 a high ionization efficiency 1826:1853 a high ionization efficiency 1826:1853 The derivatized analytes have a high ionization efficiency and they are detected with a high sensitivity in the electrospray ionization. 27590087 1 90 contain carrying 377:384 arg1 kinds 257:261 three kinds 251:261 three kinds of novel derivatization reagents (4-CEBTPP, 4-CBBTPP, 5-COTPP) with triphenylphosphine (TPP) 251:354 We have developed three kinds of novel derivatization reagents (4-CEBTPP, 4-CBBTPP, 5-COTPP) with triphenylphosphine (TPP) as a basic structure carrying a permanent positive charge for resolution of the oligosaccharides in glycoprotein using high-performance liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). 27590087 1 90 contain carrying 377:384 arg2 charge 407:412 a permanent positive charge 386:412 a permanent positive charge for resolution of the oligosaccharides in glycoprotein using high-performance liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) 386:576 We have developed three kinds of novel derivatization reagents (4-CEBTPP, 4-CBBTPP, 5-COTPP) with triphenylphosphine (TPP) as a basic structure carrying a permanent positive charge for resolution of the oligosaccharides in glycoprotein using high-performance liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). 27590087 1 90 contain carrying 377:384 arg1 structure 367:375 a basic structure 359:375 a basic structure carrying a permanent positive charge for resolution of the oligosaccharides in glycoprotein using high-performance liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) 359:576 We have developed three kinds of novel derivatization reagents (4-CEBTPP, 4-CBBTPP, 5-COTPP) with triphenylphosphine (TPP) as a basic structure carrying a permanent positive charge for resolution of the oligosaccharides in glycoprotein using high-performance liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). 27590087 4 91 theme SRM 867:869 arg1 chromatograms 871:883 the SRM chromatograms 863:883 the SRM chromatograms 863:883 Furthermore, the limits of detection (S/N=3) on the SRM chromatograms were at the fmol level (30fmol). 27590087 12 92 theme ribonuclease 2153:2164 arg1 B 2166:2166 ribonuclease B 2153:2166 ribonuclease B 2153:2166 Furthermore, several oligosaccharides in fetuin and ribonuclease B were successfully identified by the proposed procedure. 27590087 1 93 theme reagents 287:294 arg1 kinds 257:261 three kinds 251:261 three kinds of novel derivatization reagents (4-CEBTPP, 4-CBBTPP, 5-COTPP) with triphenylphosphine (TPP) 251:354 We have developed three kinds of novel derivatization reagents (4-CEBTPP, 4-CBBTPP, 5-COTPP) with triphenylphosphine (TPP) as a basic structure carrying a permanent positive charge for resolution of the oligosaccharides in glycoprotein using high-performance liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). 27590087 1 93 theme reagents 287:294 arg1 structure 367:375 a basic structure 359:375 a basic structure carrying a permanent positive charge for resolution of the oligosaccharides in glycoprotein using high-performance liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) 359:576 We have developed three kinds of novel derivatization reagents (4-CEBTPP, 4-CBBTPP, 5-COTPP) with triphenylphosphine (TPP) as a basic structure carrying a permanent positive charge for resolution of the oligosaccharides in glycoprotein using high-performance liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). 27590087 8 94 theme fragment 1442:1449 arg1 ions 1451:1454 the fragment ions 1438:1454 the fragment ions 1438:1454 Among the fragment ions, m/z 627.37 (CE=40eV) corresponding to 4-CEBTPP-GlcNAc and m/z 120.09 (CE=100eV) corresponding to 4-CEBTPP are the most important ones for identifying the oligosaccharide. 27590087 1 95 gly glycoprotein 456:467 arg1 glycoprotein 456:467 glycoprotein 456:467 glycoprotein using high-performance liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) 456:576 We have developed three kinds of novel derivatization reagents (4-CEBTPP, 4-CBBTPP, 5-COTPP) with triphenylphosphine (TPP) as a basic structure carrying a permanent positive charge for resolution of the oligosaccharides in glycoprotein using high-performance liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). 28919888 4 0 theme control 862:868 arg1 genes 870:874 endogenous control genes 851:874 endogenous control genes 851:874 Most of the quantitative methodologies used nowadays require data normalization, and this is achieved measuring the expression of endogenous control genes. 28919888 11 1 theme sucrose 2542:2548 arg1 assimilation 2550:2561 sucrose assimilation 2542:2561 sucrose assimilation 2542:2561 As a proof of concept, this gene was used to assess the expression of genes encoding for glycosidases involved in the protein N-linked glycosylation pathway, a histidine kinase whose expression is regulated during the fungal dimorphism, and a glycosidase that participates in sucrose assimilation. 28919888 2 2 theme clinical 339:346 arg1 features 348:355 basic and clinical features 329:355 basic and clinical features of this organism 329:372 The interest in basic and clinical features of this organism has significantly increased in the last years, yet little progress in molecular aspects has been reported. 28919888 10 3 theme data 2225:2228 arg1 normalization 2230:2242 data normalization 2225:2242 data normalization in expression assays 2225:2263 Therefore, this gene could be used as control for data normalization in expression assays. 28919888 2 4 from interest 317:324 arg1 features 348:355 basic and clinical features 329:355 basic and clinical features of this organism 329:372 The interest in basic and clinical features of this organism has significantly increased in the last years, yet little progress in molecular aspects has been reported. 28919888 11 5 theme concept 2280:2286 arg1 gene 2294:2297 this gene 2289:2297 this gene 2289:2297 As a proof of concept, this gene was used to assess the expression of genes encoding for glycosidases involved in the protein N-linked glycosylation pathway, a histidine kinase whose expression is regulated during the fungal dimorphism, and a glycosidase that participates in sucrose assimilation. 28919888 11 5 theme concept 2280:2286 arg1 proof 2271:2275 a proof 2269:2275 a proof of concept 2269:2286 As a proof of concept, this gene was used to assess the expression of genes encoding for glycosidases involved in the protein N-linked glycosylation pathway, a histidine kinase whose expression is regulated during the fungal dimorphism, and a glycosidase that participates in sucrose assimilation. 28919888 3 6 theme growth 702:707 arg1 conditions 709:718 different growth conditions 692:718 different growth conditions 692:718 Gene expression analysis is a set of powerful tools that helps to assess the cell response to changes in the extracellular environment, the genetic networks controlling metabolic pathways, and the adaptation to different growth conditions. 28919888 3 7 theme tools 527:531 arg1 analysis 497:504 Gene expression analysis 481:504 Gene expression analysis 481:504 Gene expression analysis is a set of powerful tools that helps to assess the cell response to changes in the extracellular environment, the genetic networks controlling metabolic pathways, and the adaptation to different growth conditions. 28919888 3 7 theme tools 527:531 arg1 set 511:513 a set 509:513 a set of powerful tools that helps to assess the cell response to changes in the extracellular environment, the genetic networks controlling metabolic pathways, and the adaptation to different growth conditions 509:718 Gene expression analysis is a set of powerful tools that helps to assess the cell response to changes in the extracellular environment, the genetic networks controlling metabolic pathways, and the adaptation to different growth conditions. 28919888 3 7 theme tools 527:531 arg1 tools 527:531 powerful tools 518:531 powerful tools 518:531 Gene expression analysis is a set of powerful tools that helps to assess the cell response to changes in the extracellular environment, the genetic networks controlling metabolic pathways, and the adaptation to different growth conditions. 28919888 9 8 theme mellonella 2131:2140 arg1 larvae 2112:2117 larvae 2112:2117 larvae of Galleria mellonella 2112:2140 Furthermore, it displayed not transcriptional changes when S. schenckii infected larvae of Galleria mellonella or interacted with immune cells. 28919888 5 9 theme conditions 1047:1056 arg1 presence 1015:1022 the presence 1011:1022 the presence of harsh extracellular conditions 1011:1056 Reference genes, whose expression is assumed to suffer minimal changes regardless the cell morphology, the stage of the cell cycle or the presence of harsh extracellular conditions are commonly used as controls in Northern blotting assays, microarrays, and semi-quantitative or quantitative RT-PCR. 28919888 5 9 theme conditions 1047:1056 arg1 morphology 968:977 the cell morphology 959:977 the cell morphology 959:977 Reference genes, whose expression is assumed to suffer minimal changes regardless the cell morphology, the stage of the cell cycle or the presence of harsh extracellular conditions are commonly used as controls in Northern blotting assays, microarrays, and semi-quantitative or quantitative RT-PCR. 28919888 5 9 theme conditions 1047:1056 arg1 stage 984:988 the stage 980:988 the stage of the cell cycle 980:1006 Reference genes, whose expression is assumed to suffer minimal changes regardless the cell morphology, the stage of the cell cycle or the presence of harsh extracellular conditions are commonly used as controls in Northern blotting assays, microarrays, and semi-quantitative or quantitative RT-PCR. 28919888 5 9 theme conditions 1047:1056 arg1 controls 1079:1086 controls 1079:1086 controls 1079:1086 Reference genes, whose expression is assumed to suffer minimal changes regardless the cell morphology, the stage of the cell cycle or the presence of harsh extracellular conditions are commonly used as controls in Northern blotting assays, microarrays, and semi-quantitative or quantitative RT-PCR. 28919888 7 10 theme transcription 1592:1604 arg1 initiation 1606:1615 transcription initiation 1592:1615 transcription initiation on Pol III promoters 1592:1636 Here, we compared the transcriptional stability of the genes encoding for elongation factor 1A, Tfc1, a protein involved in transcription initiation on Pol III promoters, ribosomal protein L6, histone H2A, β-actin, β-tubulin, glyceraldehyde 3-phosphate dehydrogenase, UAF30, the upstream activating factor 30, and the transcription initiation factor TFIID subunit 10, during the fungal growth in different culture media and cell morphologies. 28919888 5 11 used used 1071:1074 arg2 presence 1015:1022 the presence 1011:1022 the presence of harsh extracellular conditions 1011:1056 Reference genes, whose expression is assumed to suffer minimal changes regardless the cell morphology, the stage of the cell cycle or the presence of harsh extracellular conditions are commonly used as controls in Northern blotting assays, microarrays, and semi-quantitative or quantitative RT-PCR. 28919888 5 11 used used 1071:1074 arg2 morphology 968:977 the cell morphology 959:977 the cell morphology 959:977 Reference genes, whose expression is assumed to suffer minimal changes regardless the cell morphology, the stage of the cell cycle or the presence of harsh extracellular conditions are commonly used as controls in Northern blotting assays, microarrays, and semi-quantitative or quantitative RT-PCR. 28919888 5 11 used used 1071:1074 arg2 controls 1079:1086 controls 1079:1086 controls 1079:1086 Reference genes, whose expression is assumed to suffer minimal changes regardless the cell morphology, the stage of the cell cycle or the presence of harsh extracellular conditions are commonly used as controls in Northern blotting assays, microarrays, and semi-quantitative or quantitative RT-PCR. 28919888 5 11 used used 1071:1074 arg2 stage 984:988 the stage 980:988 the stage of the cell cycle 980:1006 Reference genes, whose expression is assumed to suffer minimal changes regardless the cell morphology, the stage of the cell cycle or the presence of harsh extracellular conditions are commonly used as controls in Northern blotting assays, microarrays, and semi-quantitative or quantitative RT-PCR. 28919888 6 12 theme genes 1294:1298 arg1 controls 1320:1327 controls 1320:1327 controls 1320:1327 Since the biology of the organisms is usually species specific, it is difficult to find a reliable group of universal genes that can be used as controls for data normalization in experiments addressing the gene expression, regardless the taxonomic classification of the organism under study. 28919888 6 12 theme genes 1294:1298 arg1 group 1275:1279 a reliable group 1264:1279 a reliable group of universal genes that can be used as controls for data normalization in experiments addressing the gene expression, regardless the taxonomic classification of the organism under study 1264:1465 Since the biology of the organisms is usually species specific, it is difficult to find a reliable group of universal genes that can be used as controls for data normalization in experiments addressing the gene expression, regardless the taxonomic classification of the organism under study. 28919888 6 12 theme genes 1294:1298 arg1 genes 1294:1298 universal genes 1284:1298 universal genes that can be used as controls for data normalization in experiments addressing the gene expression, regardless the taxonomic classification of the organism under study 1284:1465 Since the biology of the organisms is usually species specific, it is difficult to find a reliable group of universal genes that can be used as controls for data normalization in experiments addressing the gene expression, regardless the taxonomic classification of the organism under study. 28919888 9 13 theme immune 2161:2166 arg1 cells 2168:2172 immune cells 2161:2172 immune cells 2161:2172 Furthermore, it displayed not transcriptional changes when S. schenckii infected larvae of Galleria mellonella or interacted with immune cells. 28919888 3 14 theme cell 558:561 arg1 response 563:570 the cell response 554:570 the cell response to changes in the extracellular environment, the genetic networks controlling metabolic pathways, and the adaptation to different growth conditions 554:718 Gene expression analysis is a set of powerful tools that helps to assess the cell response to changes in the extracellular environment, the genetic networks controlling metabolic pathways, and the adaptation to different growth conditions. 28919888 7 15 theme activating 1756:1765 arg1 factor 1767:1772 the upstream activating factor 30 1743:1775 the upstream activating factor 30 1743:1775 Here, we compared the transcriptional stability of the genes encoding for elongation factor 1A, Tfc1, a protein involved in transcription initiation on Pol III promoters, ribosomal protein L6, histone H2A, β-actin, β-tubulin, glyceraldehyde 3-phosphate dehydrogenase, UAF30, the upstream activating factor 30, and the transcription initiation factor TFIID subunit 10, during the fungal growth in different culture media and cell morphologies. 28919888 7 15 theme activating 1756:1765 arg1 L6 1657:1658 ribosomal protein L6 1639:1658 ribosomal protein L6 1639:1658 Here, we compared the transcriptional stability of the genes encoding for elongation factor 1A, Tfc1, a protein involved in transcription initiation on Pol III promoters, ribosomal protein L6, histone H2A, β-actin, β-tubulin, glyceraldehyde 3-phosphate dehydrogenase, UAF30, the upstream activating factor 30, and the transcription initiation factor TFIID subunit 10, during the fungal growth in different culture media and cell morphologies. 28919888 6 16 theme reliable 1266:1273 arg1 controls 1320:1327 controls 1320:1327 controls 1320:1327 Since the biology of the organisms is usually species specific, it is difficult to find a reliable group of universal genes that can be used as controls for data normalization in experiments addressing the gene expression, regardless the taxonomic classification of the organism under study. 28919888 6 16 theme reliable 1266:1273 arg1 group 1275:1279 a reliable group 1264:1279 a reliable group of universal genes that can be used as controls for data normalization in experiments addressing the gene expression, regardless the taxonomic classification of the organism under study 1264:1465 Since the biology of the organisms is usually species specific, it is difficult to find a reliable group of universal genes that can be used as controls for data normalization in experiments addressing the gene expression, regardless the taxonomic classification of the organism under study. 28919888 6 16 theme reliable 1266:1273 arg1 genes 1294:1298 universal genes 1284:1298 universal genes that can be used as controls for data normalization in experiments addressing the gene expression, regardless the taxonomic classification of the organism under study 1284:1465 Since the biology of the organisms is usually species specific, it is difficult to find a reliable group of universal genes that can be used as controls for data normalization in experiments addressing the gene expression, regardless the taxonomic classification of the organism under study. 28919888 5 17 theme harsh 1027:1031 arg1 conditions 1047:1056 harsh extracellular conditions 1027:1056 harsh extracellular conditions 1027:1056 Reference genes, whose expression is assumed to suffer minimal changes regardless the cell morphology, the stage of the cell cycle or the presence of harsh extracellular conditions are commonly used as controls in Northern blotting assays, microarrays, and semi-quantitative or quantitative RT-PCR. 28919888 3 18 theme extracellular 590:602 arg1 environment 604:614 the extracellular environment 586:614 the extracellular environment 586:614 Gene expression analysis is a set of powerful tools that helps to assess the cell response to changes in the extracellular environment, the genetic networks controlling metabolic pathways, and the adaptation to different growth conditions. 28919888 11 19 theme fungal 2484:2489 arg1 dimorphism 2491:2500 the fungal dimorphism 2480:2500 the fungal dimorphism 2480:2500 As a proof of concept, this gene was used to assess the expression of genes encoding for glycosidases involved in the protein N-linked glycosylation pathway, a histidine kinase whose expression is regulated during the fungal dimorphism, and a glycosidase that participates in sucrose assimilation. 28919888 11 20 theme protein 2384:2390 arg1 pathway 2415:2421 the protein N-linked glycosylation pathway 2380:2421 the protein N-linked glycosylation pathway 2380:2421 As a proof of concept, this gene was used to assess the expression of genes encoding for glycosidases involved in the protein N-linked glycosylation pathway, a histidine kinase whose expression is regulated during the fungal dimorphism, and a glycosidase that participates in sucrose assimilation. 28919888 0 21 theme Protein 57:63 arg1 L6 65:66 the Ribosomal Protein L6 43:66 the Ribosomal Protein L6 43:66 The Sporothrix schenckii Gene Encoding for the Ribosomal Protein L6 Has Constitutive and Stable Expression and Works as an Endogenous Control in Gene Expression Analysis. 28919888 6 22 from normalization 1338:1350 arg1 experiments 1355:1365 experiments 1355:1365 experiments addressing the gene expression, regardless the taxonomic classification of the organism under study 1355:1465 Since the biology of the organisms is usually species specific, it is difficult to find a reliable group of universal genes that can be used as controls for data normalization in experiments addressing the gene expression, regardless the taxonomic classification of the organism under study. 28919888 8 23 theme ribosomal 1969:1977 arg1 L6 1987:1988 the ribosomal protein L6 1965:1988 the ribosomal protein L6 1965:1988 Our results indicated that only the gene encoding for the ribosomal protein L6 showed a stable and constant expression. 28919888 0 24 theme Gene 145:148 arg1 Analysis 161:168 Gene Expression Analysis 145:168 Gene Expression Analysis 145:168 The Sporothrix schenckii Gene Encoding for the Ribosomal Protein L6 Has Constitutive and Stable Expression and Works as an Endogenous Control in Gene Expression Analysis. 28919888 5 25 dep suffer 925:930 arg1 used 1071:1074 used 1071:1074 are commonly used as controls in Northern blotting assays, microarrays, and semi-quantitative or quantitative RT-PCR 1058:1173 Reference genes, whose expression is assumed to suffer minimal changes regardless the cell morphology, the stage of the cell cycle or the presence of harsh extracellular conditions are commonly used as controls in Northern blotting assays, microarrays, and semi-quantitative or quantitative RT-PCR. 28919888 6 26 theme data 1333:1336 arg1 normalization 1338:1350 data normalization 1333:1350 data normalization in experiments addressing the gene expression, regardless the taxonomic classification of the organism under study 1333:1465 Since the biology of the organisms is usually species specific, it is difficult to find a reliable group of universal genes that can be used as controls for data normalization in experiments addressing the gene expression, regardless the taxonomic classification of the organism under study. 28919888 7 27 theme histone 1661:1667 arg1 L6 1657:1658 ribosomal protein L6 1639:1658 ribosomal protein L6 1639:1658 Here, we compared the transcriptional stability of the genes encoding for elongation factor 1A, Tfc1, a protein involved in transcription initiation on Pol III promoters, ribosomal protein L6, histone H2A, β-actin, β-tubulin, glyceraldehyde 3-phosphate dehydrogenase, UAF30, the upstream activating factor 30, and the transcription initiation factor TFIID subunit 10, during the fungal growth in different culture media and cell morphologies. 28919888 7 27 theme histone 1661:1667 arg1 H2A 1669:1671 histone H2A 1661:1671 histone H2A 1661:1671 Here, we compared the transcriptional stability of the genes encoding for elongation factor 1A, Tfc1, a protein involved in transcription initiation on Pol III promoters, ribosomal protein L6, histone H2A, β-actin, β-tubulin, glyceraldehyde 3-phosphate dehydrogenase, UAF30, the upstream activating factor 30, and the transcription initiation factor TFIID subunit 10, during the fungal growth in different culture media and cell morphologies. 28919888 7 28 theme elongation 1542:1551 arg1 1A 1560:1561 elongation factor 1A 1542:1561 elongation factor 1A 1542:1561 Here, we compared the transcriptional stability of the genes encoding for elongation factor 1A, Tfc1, a protein involved in transcription initiation on Pol III promoters, ribosomal protein L6, histone H2A, β-actin, β-tubulin, glyceraldehyde 3-phosphate dehydrogenase, UAF30, the upstream activating factor 30, and the transcription initiation factor TFIID subunit 10, during the fungal growth in different culture media and cell morphologies. 28919888 11 29 theme glycosylation 2401:2413 arg1 pathway 2415:2421 the protein N-linked glycosylation pathway 2380:2421 the protein N-linked glycosylation pathway 2380:2421 As a proof of concept, this gene was used to assess the expression of genes encoding for glycosidases involved in the protein N-linked glycosylation pathway, a histidine kinase whose expression is regulated during the fungal dimorphism, and a glycosidase that participates in sucrose assimilation. 28919888 7 30 theme cell 1892:1895 arg1 morphologies 1897:1908 cell morphologies 1892:1908 cell morphologies 1892:1908 Here, we compared the transcriptional stability of the genes encoding for elongation factor 1A, Tfc1, a protein involved in transcription initiation on Pol III promoters, ribosomal protein L6, histone H2A, β-actin, β-tubulin, glyceraldehyde 3-phosphate dehydrogenase, UAF30, the upstream activating factor 30, and the transcription initiation factor TFIID subunit 10, during the fungal growth in different culture media and cell morphologies. 28919888 5 31 theme cell 963:966 arg1 presence 1015:1022 the presence 1011:1022 the presence of harsh extracellular conditions 1011:1056 Reference genes, whose expression is assumed to suffer minimal changes regardless the cell morphology, the stage of the cell cycle or the presence of harsh extracellular conditions are commonly used as controls in Northern blotting assays, microarrays, and semi-quantitative or quantitative RT-PCR. 28919888 5 31 theme cell 963:966 arg1 morphology 968:977 the cell morphology 959:977 the cell morphology 959:977 Reference genes, whose expression is assumed to suffer minimal changes regardless the cell morphology, the stage of the cell cycle or the presence of harsh extracellular conditions are commonly used as controls in Northern blotting assays, microarrays, and semi-quantitative or quantitative RT-PCR. 28919888 5 31 theme cell 963:966 arg1 controls 1079:1086 controls 1079:1086 controls 1079:1086 Reference genes, whose expression is assumed to suffer minimal changes regardless the cell morphology, the stage of the cell cycle or the presence of harsh extracellular conditions are commonly used as controls in Northern blotting assays, microarrays, and semi-quantitative or quantitative RT-PCR. 28919888 5 31 theme cell 963:966 arg1 stage 984:988 the stage 980:988 the stage of the cell cycle 980:1006 Reference genes, whose expression is assumed to suffer minimal changes regardless the cell morphology, the stage of the cell cycle or the presence of harsh extracellular conditions are commonly used as controls in Northern blotting assays, microarrays, and semi-quantitative or quantitative RT-PCR. 28919888 7 32 from growth 1854:1859 arg1 media 1882:1886 different culture media 1864:1886 different culture media 1864:1886 Here, we compared the transcriptional stability of the genes encoding for elongation factor 1A, Tfc1, a protein involved in transcription initiation on Pol III promoters, ribosomal protein L6, histone H2A, β-actin, β-tubulin, glyceraldehyde 3-phosphate dehydrogenase, UAF30, the upstream activating factor 30, and the transcription initiation factor TFIID subunit 10, during the fungal growth in different culture media and cell morphologies. 28919888 7 32 from growth 1854:1859 arg1 morphologies 1897:1908 cell morphologies 1892:1908 cell morphologies 1892:1908 Here, we compared the transcriptional stability of the genes encoding for elongation factor 1A, Tfc1, a protein involved in transcription initiation on Pol III promoters, ribosomal protein L6, histone H2A, β-actin, β-tubulin, glyceraldehyde 3-phosphate dehydrogenase, UAF30, the upstream activating factor 30, and the transcription initiation factor TFIID subunit 10, during the fungal growth in different culture media and cell morphologies. 28919888 7 33 theme ribosomal 1639:1647 arg1 protein 1572:1578 a protein 1570:1578 a protein involved in transcription initiation on Pol III promoters 1570:1636 Here, we compared the transcriptional stability of the genes encoding for elongation factor 1A, Tfc1, a protein involved in transcription initiation on Pol III promoters, ribosomal protein L6, histone H2A, β-actin, β-tubulin, glyceraldehyde 3-phosphate dehydrogenase, UAF30, the upstream activating factor 30, and the transcription initiation factor TFIID subunit 10, during the fungal growth in different culture media and cell morphologies. 28919888 7 33 theme ribosomal 1639:1647 arg1 β-tubulin 1683:1691 β-tubulin 1683:1691 β-tubulin 1683:1691 Here, we compared the transcriptional stability of the genes encoding for elongation factor 1A, Tfc1, a protein involved in transcription initiation on Pol III promoters, ribosomal protein L6, histone H2A, β-actin, β-tubulin, glyceraldehyde 3-phosphate dehydrogenase, UAF30, the upstream activating factor 30, and the transcription initiation factor TFIID subunit 10, during the fungal growth in different culture media and cell morphologies. 28919888 7 33 theme ribosomal 1639:1647 arg1 H2A 1669:1671 histone H2A 1661:1671 histone H2A 1661:1671 Here, we compared the transcriptional stability of the genes encoding for elongation factor 1A, Tfc1, a protein involved in transcription initiation on Pol III promoters, ribosomal protein L6, histone H2A, β-actin, β-tubulin, glyceraldehyde 3-phosphate dehydrogenase, UAF30, the upstream activating factor 30, and the transcription initiation factor TFIID subunit 10, during the fungal growth in different culture media and cell morphologies. 28919888 7 33 theme ribosomal 1639:1647 arg1 β-actin 1674:1680 β-actin 1674:1680 β-actin 1674:1680 Here, we compared the transcriptional stability of the genes encoding for elongation factor 1A, Tfc1, a protein involved in transcription initiation on Pol III promoters, ribosomal protein L6, histone H2A, β-actin, β-tubulin, glyceraldehyde 3-phosphate dehydrogenase, UAF30, the upstream activating factor 30, and the transcription initiation factor TFIID subunit 10, during the fungal growth in different culture media and cell morphologies. 28919888 7 33 theme ribosomal 1639:1647 arg1 dehydrogenase 1721:1733 glyceraldehyde 3-phosphate dehydrogenase 1694:1733 glyceraldehyde 3-phosphate dehydrogenase 1694:1733 Here, we compared the transcriptional stability of the genes encoding for elongation factor 1A, Tfc1, a protein involved in transcription initiation on Pol III promoters, ribosomal protein L6, histone H2A, β-actin, β-tubulin, glyceraldehyde 3-phosphate dehydrogenase, UAF30, the upstream activating factor 30, and the transcription initiation factor TFIID subunit 10, during the fungal growth in different culture media and cell morphologies. 28919888 7 33 theme ribosomal 1639:1647 arg1 factor 1767:1772 the upstream activating factor 30 1743:1775 the upstream activating factor 30 1743:1775 Here, we compared the transcriptional stability of the genes encoding for elongation factor 1A, Tfc1, a protein involved in transcription initiation on Pol III promoters, ribosomal protein L6, histone H2A, β-actin, β-tubulin, glyceraldehyde 3-phosphate dehydrogenase, UAF30, the upstream activating factor 30, and the transcription initiation factor TFIID subunit 10, during the fungal growth in different culture media and cell morphologies. 28919888 7 33 theme ribosomal 1639:1647 arg1 UAF30 1736:1740 UAF30 1736:1740 UAF30 1736:1740 Here, we compared the transcriptional stability of the genes encoding for elongation factor 1A, Tfc1, a protein involved in transcription initiation on Pol III promoters, ribosomal protein L6, histone H2A, β-actin, β-tubulin, glyceraldehyde 3-phosphate dehydrogenase, UAF30, the upstream activating factor 30, and the transcription initiation factor TFIID subunit 10, during the fungal growth in different culture media and cell morphologies. 28919888 7 33 theme ribosomal 1639:1647 arg1 L6 1657:1658 ribosomal protein L6 1639:1658 ribosomal protein L6 1639:1658 Here, we compared the transcriptional stability of the genes encoding for elongation factor 1A, Tfc1, a protein involved in transcription initiation on Pol III promoters, ribosomal protein L6, histone H2A, β-actin, β-tubulin, glyceraldehyde 3-phosphate dehydrogenase, UAF30, the upstream activating factor 30, and the transcription initiation factor TFIID subunit 10, during the fungal growth in different culture media and cell morphologies. 28919888 11 34 theme histidine 2426:2434 arg1 kinase 2436:2441 a histidine kinase 2424:2441 a histidine kinase whose expression is regulated during the fungal dimorphism 2424:2500 As a proof of concept, this gene was used to assess the expression of genes encoding for glycosidases involved in the protein N-linked glycosylation pathway, a histidine kinase whose expression is regulated during the fungal dimorphism, and a glycosidase that participates in sucrose assimilation. 28919888 10 35 used used 2205:2208 arg2 gene 2191:2194 this gene 2186:2194 this gene 2186:2194 Therefore, this gene could be used as control for data normalization in expression assays. 28919888 10 35 used used 2205:2208 arg2 control 2213:2219 control 2213:2219 control 2213:2219 Therefore, this gene could be used as control for data normalization in expression assays. 28919888 5 36 theme quantitative 1155:1166 arg1 RT-PCR 1168:1173 semi-quantitative or quantitative RT-PCR 1134:1173 semi-quantitative or quantitative RT-PCR 1134:1173 Reference genes, whose expression is assumed to suffer minimal changes regardless the cell morphology, the stage of the cell cycle or the presence of harsh extracellular conditions are commonly used as controls in Northern blotting assays, microarrays, and semi-quantitative or quantitative RT-PCR. 28919888 7 37 theme different 1864:1872 arg1 media 1882:1886 different culture media 1864:1886 different culture media 1864:1886 Here, we compared the transcriptional stability of the genes encoding for elongation factor 1A, Tfc1, a protein involved in transcription initiation on Pol III promoters, ribosomal protein L6, histone H2A, β-actin, β-tubulin, glyceraldehyde 3-phosphate dehydrogenase, UAF30, the upstream activating factor 30, and the transcription initiation factor TFIID subunit 10, during the fungal growth in different culture media and cell morphologies. 28919888 5 38 theme minimal 932:938 arg1 changes 940:946 minimal changes 932:946 minimal changes 932:946 Reference genes, whose expression is assumed to suffer minimal changes regardless the cell morphology, the stage of the cell cycle or the presence of harsh extracellular conditions are commonly used as controls in Northern blotting assays, microarrays, and semi-quantitative or quantitative RT-PCR. 28919888 11 39 link N-linked 2392:2399 arg1 pathway 2415:2421 the protein N-linked glycosylation pathway 2380:2421 the protein N-linked glycosylation pathway 2380:2421 As a proof of concept, this gene was used to assess the expression of genes encoding for glycosidases involved in the protein N-linked glycosylation pathway, a histidine kinase whose expression is regulated during the fungal dimorphism, and a glycosidase that participates in sucrose assimilation. 28919888 0 40 theme schenckii 15:23 arg1 Gene 25:28 The Sporothrix schenckii Gene 0:28 The Sporothrix schenckii Gene Encoding for the Ribosomal Protein L6 0:66 The Sporothrix schenckii Gene Encoding for the Ribosomal Protein L6 Has Constitutive and Stable Expression and Works as an Endogenous Control in Gene Expression Analysis. 28919888 7 41 theme Pol 1620:1622 arg1 promoters 1628:1636 Pol III promoters 1620:1636 Pol III promoters 1620:1636 Here, we compared the transcriptional stability of the genes encoding for elongation factor 1A, Tfc1, a protein involved in transcription initiation on Pol III promoters, ribosomal protein L6, histone H2A, β-actin, β-tubulin, glyceraldehyde 3-phosphate dehydrogenase, UAF30, the upstream activating factor 30, and the transcription initiation factor TFIID subunit 10, during the fungal growth in different culture media and cell morphologies. 28919888 3 42 theme genetic 621:627 arg1 networks 629:636 the genetic networks 617:636 the genetic networks controlling metabolic pathways 617:667 Gene expression analysis is a set of powerful tools that helps to assess the cell response to changes in the extracellular environment, the genetic networks controlling metabolic pathways, and the adaptation to different growth conditions. 28919888 6 43 theme gene 1382:1385 arg1 classification 1424:1437 the taxonomic classification 1410:1437 the taxonomic classification of the organism under study 1410:1465 Since the biology of the organisms is usually species specific, it is difficult to find a reliable group of universal genes that can be used as controls for data normalization in experiments addressing the gene expression, regardless the taxonomic classification of the organism under study. 28919888 6 43 theme gene 1382:1385 arg1 expression 1387:1396 the gene expression 1378:1396 the gene expression 1378:1396 Since the biology of the organisms is usually species specific, it is difficult to find a reliable group of universal genes that can be used as controls for data normalization in experiments addressing the gene expression, regardless the taxonomic classification of the organism under study. 28919888 1 44 theme other 298:302 arg1 mammals 304:310 other mammals 298:310 other mammals 298:310 Sporothrix schenckii is one of the causative agents of sporotrichosis, a worldwide-distributed mycosis that affects humans and other mammals. 28919888 7 45 theme transcriptional 1490:1504 arg1 stability 1506:1514 the transcriptional stability 1486:1514 the transcriptional stability of the genes encoding for elongation factor 1A, Tfc1, a protein involved in transcription initiation on Pol III promoters, ribosomal protein L6, histone H2A, β-actin, β-tubulin, glyceraldehyde 3-phosphate dehydrogenase, UAF30, the upstream activating factor 30, and the transcription initiation factor TFIID subunit 10 1486:1833 Here, we compared the transcriptional stability of the genes encoding for elongation factor 1A, Tfc1, a protein involved in transcription initiation on Pol III promoters, ribosomal protein L6, histone H2A, β-actin, β-tubulin, glyceraldehyde 3-phosphate dehydrogenase, UAF30, the upstream activating factor 30, and the transcription initiation factor TFIID subunit 10, during the fungal growth in different culture media and cell morphologies. 28919888 5 46 theme cycle 1002:1006 arg1 presence 1015:1022 the presence 1011:1022 the presence of harsh extracellular conditions 1011:1056 Reference genes, whose expression is assumed to suffer minimal changes regardless the cell morphology, the stage of the cell cycle or the presence of harsh extracellular conditions are commonly used as controls in Northern blotting assays, microarrays, and semi-quantitative or quantitative RT-PCR. 28919888 5 46 theme cycle 1002:1006 arg1 morphology 968:977 the cell morphology 959:977 the cell morphology 959:977 Reference genes, whose expression is assumed to suffer minimal changes regardless the cell morphology, the stage of the cell cycle or the presence of harsh extracellular conditions are commonly used as controls in Northern blotting assays, microarrays, and semi-quantitative or quantitative RT-PCR. 28919888 5 46 theme cycle 1002:1006 arg1 stage 984:988 the stage 980:988 the stage of the cell cycle 980:1006 Reference genes, whose expression is assumed to suffer minimal changes regardless the cell morphology, the stage of the cell cycle or the presence of harsh extracellular conditions are commonly used as controls in Northern blotting assays, microarrays, and semi-quantitative or quantitative RT-PCR. 28919888 5 46 theme cycle 1002:1006 arg1 controls 1079:1086 controls 1079:1086 controls 1079:1086 Reference genes, whose expression is assumed to suffer minimal changes regardless the cell morphology, the stage of the cell cycle or the presence of harsh extracellular conditions are commonly used as controls in Northern blotting assays, microarrays, and semi-quantitative or quantitative RT-PCR. 28919888 7 47 theme initiation 1800:1809 arg1 subunit 1824:1830 the transcription initiation factor TFIID subunit 10 1782:1833 the transcription initiation factor TFIID subunit 10 1782:1833 Here, we compared the transcriptional stability of the genes encoding for elongation factor 1A, Tfc1, a protein involved in transcription initiation on Pol III promoters, ribosomal protein L6, histone H2A, β-actin, β-tubulin, glyceraldehyde 3-phosphate dehydrogenase, UAF30, the upstream activating factor 30, and the transcription initiation factor TFIID subunit 10, during the fungal growth in different culture media and cell morphologies. 28919888 2 48 theme molecular 444:452 arg1 aspects 454:460 molecular aspects 444:460 molecular aspects 444:460 The interest in basic and clinical features of this organism has significantly increased in the last years, yet little progress in molecular aspects has been reported. 28919888 10 49 from normalization 2230:2242 arg1 assays 2258:2263 expression assays 2247:2263 expression assays 2247:2263 Therefore, this gene could be used as control for data normalization in expression assays. 28919888 5 50 theme semi-quantitative 1134:1150 arg1 RT-PCR 1168:1173 semi-quantitative or quantitative RT-PCR 1134:1173 semi-quantitative or quantitative RT-PCR 1134:1173 Reference genes, whose expression is assumed to suffer minimal changes regardless the cell morphology, the stage of the cell cycle or the presence of harsh extracellular conditions are commonly used as controls in Northern blotting assays, microarrays, and semi-quantitative or quantitative RT-PCR. 28919888 5 51 theme blotting 1100:1107 arg1 assays 1109:1114 Northern blotting assays 1091:1114 Northern blotting assays 1091:1114 Reference genes, whose expression is assumed to suffer minimal changes regardless the cell morphology, the stage of the cell cycle or the presence of harsh extracellular conditions are commonly used as controls in Northern blotting assays, microarrays, and semi-quantitative or quantitative RT-PCR. 28919888 4 52 theme data 782:785 arg1 normalization 787:799 data normalization 782:799 data normalization 782:799 Most of the quantitative methodologies used nowadays require data normalization, and this is achieved measuring the expression of endogenous control genes. 28919888 1 53 theme causative 206:214 arg1 agents 216:221 the causative agents 202:221 the causative agents of sporotrichosis, a worldwide-distributed mycosis that affects humans and other mammals 202:310 Sporothrix schenckii is one of the causative agents of sporotrichosis, a worldwide-distributed mycosis that affects humans and other mammals. 28919888 6 54 dep specific 1230:1237 arg1 specific 1230:1237 specific 1230:1237 specific 1230:1237 Since the biology of the organisms is usually species specific, it is difficult to find a reliable group of universal genes that can be used as controls for data normalization in experiments addressing the gene expression, regardless the taxonomic classification of the organism under study. 28919888 6 54 dep specific 1230:1237 arg1 biology 1186:1192 the biology 1182:1192 the biology of the organisms 1182:1209 Since the biology of the organisms is usually species specific, it is difficult to find a reliable group of universal genes that can be used as controls for data normalization in experiments addressing the gene expression, regardless the taxonomic classification of the organism under study. 28919888 6 54 dep specific 1230:1237 arg1 species 1222:1228 species 1222:1228 species 1222:1228 Since the biology of the organisms is usually species specific, it is difficult to find a reliable group of universal genes that can be used as controls for data normalization in experiments addressing the gene expression, regardless the taxonomic classification of the organism under study. 28919888 6 55 used used 1312:1315 arg2 genes 1294:1298 universal genes 1284:1298 universal genes that can be used as controls for data normalization in experiments addressing the gene expression, regardless the taxonomic classification of the organism under study 1284:1465 Since the biology of the organisms is usually species specific, it is difficult to find a reliable group of universal genes that can be used as controls for data normalization in experiments addressing the gene expression, regardless the taxonomic classification of the organism under study. 28919888 6 55 used used 1312:1315 arg2 controls 1320:1327 controls 1320:1327 controls 1320:1327 Since the biology of the organisms is usually species specific, it is difficult to find a reliable group of universal genes that can be used as controls for data normalization in experiments addressing the gene expression, regardless the taxonomic classification of the organism under study. 28919888 9 56 theme transcriptional 2061:2075 arg1 changes 2077:2083 transcriptional changes 2061:2083 transcriptional changes 2061:2083 Furthermore, it displayed not transcriptional changes when S. schenckii infected larvae of Galleria mellonella or interacted with immune cells. 28919888 3 57 theme expression 486:495 arg1 analysis 497:504 Gene expression analysis 481:504 Gene expression analysis 481:504 Gene expression analysis is a set of powerful tools that helps to assess the cell response to changes in the extracellular environment, the genetic networks controlling metabolic pathways, and the adaptation to different growth conditions. 28919888 3 57 theme expression 486:495 arg1 set 511:513 a set 509:513 a set of powerful tools that helps to assess the cell response to changes in the extracellular environment, the genetic networks controlling metabolic pathways, and the adaptation to different growth conditions 509:718 Gene expression analysis is a set of powerful tools that helps to assess the cell response to changes in the extracellular environment, the genetic networks controlling metabolic pathways, and the adaptation to different growth conditions. 28919888 3 57 theme expression 486:495 arg1 tools 527:531 powerful tools 518:531 powerful tools 518:531 Gene expression analysis is a set of powerful tools that helps to assess the cell response to changes in the extracellular environment, the genetic networks controlling metabolic pathways, and the adaptation to different growth conditions. 28919888 4 58 theme endogenous 851:860 arg1 genes 870:874 endogenous control genes 851:874 endogenous control genes 851:874 Most of the quantitative methodologies used nowadays require data normalization, and this is achieved measuring the expression of endogenous control genes. 28919888 7 59 theme upstream 1747:1754 arg1 factor 1767:1772 the upstream activating factor 30 1743:1775 the upstream activating factor 30 1743:1775 Here, we compared the transcriptional stability of the genes encoding for elongation factor 1A, Tfc1, a protein involved in transcription initiation on Pol III promoters, ribosomal protein L6, histone H2A, β-actin, β-tubulin, glyceraldehyde 3-phosphate dehydrogenase, UAF30, the upstream activating factor 30, and the transcription initiation factor TFIID subunit 10, during the fungal growth in different culture media and cell morphologies. 28919888 7 59 theme upstream 1747:1754 arg1 L6 1657:1658 ribosomal protein L6 1639:1658 ribosomal protein L6 1639:1658 Here, we compared the transcriptional stability of the genes encoding for elongation factor 1A, Tfc1, a protein involved in transcription initiation on Pol III promoters, ribosomal protein L6, histone H2A, β-actin, β-tubulin, glyceraldehyde 3-phosphate dehydrogenase, UAF30, the upstream activating factor 30, and the transcription initiation factor TFIID subunit 10, during the fungal growth in different culture media and cell morphologies. 28919888 8 60 theme stable 1999:2004 arg1 expression 2019:2028 a stable and constant expression 1997:2028 a stable and constant expression 1997:2028 Our results indicated that only the gene encoding for the ribosomal protein L6 showed a stable and constant expression. 28919888 3 61 theme powerful 518:525 arg1 tools 527:531 powerful tools 518:531 powerful tools 518:531 Gene expression analysis is a set of powerful tools that helps to assess the cell response to changes in the extracellular environment, the genetic networks controlling metabolic pathways, and the adaptation to different growth conditions. 28919888 1 62 theme worldwide-distributed 244:264 arg1 sporotrichosis 226:239 sporotrichosis 226:239 sporotrichosis 226:239 Sporothrix schenckii is one of the causative agents of sporotrichosis, a worldwide-distributed mycosis that affects humans and other mammals. 28919888 1 62 theme worldwide-distributed 244:264 arg1 mycosis 266:272 a worldwide-distributed mycosis 242:272 a worldwide-distributed mycosis that affects humans and other mammals 242:310 Sporothrix schenckii is one of the causative agents of sporotrichosis, a worldwide-distributed mycosis that affects humans and other mammals. 28919888 4 63 theme genes 870:874 arg1 expression 837:846 the expression 833:846 the expression of endogenous control genes 833:874 Most of the quantitative methodologies used nowadays require data normalization, and this is achieved measuring the expression of endogenous control genes. 28919888 0 64 from Control 134:140 arg1 Analysis 161:168 Gene Expression Analysis 145:168 Gene Expression Analysis 145:168 The Sporothrix schenckii Gene Encoding for the Ribosomal Protein L6 Has Constitutive and Stable Expression and Works as an Endogenous Control in Gene Expression Analysis. 28919888 10 65 theme expression 2247:2256 arg1 assays 2258:2263 expression assays 2247:2263 expression assays 2247:2263 Therefore, this gene could be used as control for data normalization in expression assays. 28919888 3 66 theme different 692:700 arg1 conditions 709:718 different growth conditions 692:718 different growth conditions 692:718 Gene expression analysis is a set of powerful tools that helps to assess the cell response to changes in the extracellular environment, the genetic networks controlling metabolic pathways, and the adaptation to different growth conditions. 28919888 1 67 theme Sporothrix 171:180 arg1 schenckii 182:190 Sporothrix schenckii 171:190 Sporothrix schenckii 171:190 Sporothrix schenckii is one of the causative agents of sporotrichosis, a worldwide-distributed mycosis that affects humans and other mammals. 28919888 11 68 theme N-linked 2392:2399 arg1 pathway 2415:2421 the protein N-linked glycosylation pathway 2380:2421 the protein N-linked glycosylation pathway 2380:2421 As a proof of concept, this gene was used to assess the expression of genes encoding for glycosidases involved in the protein N-linked glycosylation pathway, a histidine kinase whose expression is regulated during the fungal dimorphism, and a glycosidase that participates in sucrose assimilation. 28919888 7 69 theme 3-phosphate 1709:1719 arg1 L6 1657:1658 ribosomal protein L6 1639:1658 ribosomal protein L6 1639:1658 Here, we compared the transcriptional stability of the genes encoding for elongation factor 1A, Tfc1, a protein involved in transcription initiation on Pol III promoters, ribosomal protein L6, histone H2A, β-actin, β-tubulin, glyceraldehyde 3-phosphate dehydrogenase, UAF30, the upstream activating factor 30, and the transcription initiation factor TFIID subunit 10, during the fungal growth in different culture media and cell morphologies. 28919888 7 69 theme 3-phosphate 1709:1719 arg1 dehydrogenase 1721:1733 glyceraldehyde 3-phosphate dehydrogenase 1694:1733 glyceraldehyde 3-phosphate dehydrogenase 1694:1733 Here, we compared the transcriptional stability of the genes encoding for elongation factor 1A, Tfc1, a protein involved in transcription initiation on Pol III promoters, ribosomal protein L6, histone H2A, β-actin, β-tubulin, glyceraldehyde 3-phosphate dehydrogenase, UAF30, the upstream activating factor 30, and the transcription initiation factor TFIID subunit 10, during the fungal growth in different culture media and cell morphologies. 28919888 9 70 theme Galleria 2122:2129 arg1 mellonella 2131:2140 Galleria mellonella 2122:2140 Galleria mellonella 2122:2140 Furthermore, it displayed not transcriptional changes when S. schenckii infected larvae of Galleria mellonella or interacted with immune cells. 28919888 2 71 theme basic 329:333 arg1 features 348:355 basic and clinical features 329:355 basic and clinical features of this organism 329:372 The interest in basic and clinical features of this organism has significantly increased in the last years, yet little progress in molecular aspects has been reported. 28919888 0 72 theme Endogenous 123:132 arg1 Control 134:140 an Endogenous Control 120:140 an Endogenous Control in Gene Expression Analysis 120:168 The Sporothrix schenckii Gene Encoding for the Ribosomal Protein L6 Has Constitutive and Stable Expression and Works as an Endogenous Control in Gene Expression Analysis. 28919888 6 73 theme universal 1284:1292 arg1 controls 1320:1327 controls 1320:1327 controls 1320:1327 Since the biology of the organisms is usually species specific, it is difficult to find a reliable group of universal genes that can be used as controls for data normalization in experiments addressing the gene expression, regardless the taxonomic classification of the organism under study. 28919888 6 73 theme universal 1284:1292 arg1 genes 1294:1298 universal genes 1284:1298 universal genes that can be used as controls for data normalization in experiments addressing the gene expression, regardless the taxonomic classification of the organism under study 1284:1465 Since the biology of the organisms is usually species specific, it is difficult to find a reliable group of universal genes that can be used as controls for data normalization in experiments addressing the gene expression, regardless the taxonomic classification of the organism under study. 28919888 6 74 theme organisms 1201:1209 arg1 specific 1230:1237 specific 1230:1237 specific 1230:1237 Since the biology of the organisms is usually species specific, it is difficult to find a reliable group of universal genes that can be used as controls for data normalization in experiments addressing the gene expression, regardless the taxonomic classification of the organism under study. 28919888 6 74 theme organisms 1201:1209 arg1 biology 1186:1192 the biology 1182:1192 the biology of the organisms 1182:1209 Since the biology of the organisms is usually species specific, it is difficult to find a reliable group of universal genes that can be used as controls for data normalization in experiments addressing the gene expression, regardless the taxonomic classification of the organism under study. 28919888 6 74 theme organisms 1201:1209 arg1 species 1222:1228 species 1222:1228 species 1222:1228 Since the biology of the organisms is usually species specific, it is difficult to find a reliable group of universal genes that can be used as controls for data normalization in experiments addressing the gene expression, regardless the taxonomic classification of the organism under study. 28919888 11 75 theme genes 2336:2340 arg1 expression 2322:2331 the expression 2318:2331 the expression of genes encoding for glycosidases involved in the protein N-linked glycosylation pathway, a histidine kinase whose expression is regulated during the fungal dimorphism, and a glycosidase that participates in sucrose assimilation 2318:2561 As a proof of concept, this gene was used to assess the expression of genes encoding for glycosidases involved in the protein N-linked glycosylation pathway, a histidine kinase whose expression is regulated during the fungal dimorphism, and a glycosidase that participates in sucrose assimilation. 28919888 0 76 theme Expression 150:159 arg1 Analysis 161:168 Gene Expression Analysis 145:168 Gene Expression Analysis 145:168 The Sporothrix schenckii Gene Encoding for the Ribosomal Protein L6 Has Constitutive and Stable Expression and Works as an Endogenous Control in Gene Expression Analysis. 28919888 7 77 theme glyceraldehyde 1694:1707 arg1 L6 1657:1658 ribosomal protein L6 1639:1658 ribosomal protein L6 1639:1658 Here, we compared the transcriptional stability of the genes encoding for elongation factor 1A, Tfc1, a protein involved in transcription initiation on Pol III promoters, ribosomal protein L6, histone H2A, β-actin, β-tubulin, glyceraldehyde 3-phosphate dehydrogenase, UAF30, the upstream activating factor 30, and the transcription initiation factor TFIID subunit 10, during the fungal growth in different culture media and cell morphologies. 28919888 7 77 theme glyceraldehyde 1694:1707 arg1 dehydrogenase 1721:1733 glyceraldehyde 3-phosphate dehydrogenase 1694:1733 glyceraldehyde 3-phosphate dehydrogenase 1694:1733 Here, we compared the transcriptional stability of the genes encoding for elongation factor 1A, Tfc1, a protein involved in transcription initiation on Pol III promoters, ribosomal protein L6, histone H2A, β-actin, β-tubulin, glyceraldehyde 3-phosphate dehydrogenase, UAF30, the upstream activating factor 30, and the transcription initiation factor TFIID subunit 10, during the fungal growth in different culture media and cell morphologies. 28919888 11 78 used used 2303:2306 arg2 gene 2294:2297 this gene 2289:2297 this gene 2289:2297 As a proof of concept, this gene was used to assess the expression of genes encoding for glycosidases involved in the protein N-linked glycosylation pathway, a histidine kinase whose expression is regulated during the fungal dimorphism, and a glycosidase that participates in sucrose assimilation. 28919888 11 78 used used 2303:2306 arg2 proof 2271:2275 a proof 2269:2275 a proof of concept 2269:2286 As a proof of concept, this gene was used to assess the expression of genes encoding for glycosidases involved in the protein N-linked glycosylation pathway, a histidine kinase whose expression is regulated during the fungal dimorphism, and a glycosidase that participates in sucrose assimilation. 28919888 5 79 theme extracellular 1033:1045 arg1 conditions 1047:1056 harsh extracellular conditions 1027:1056 harsh extracellular conditions 1027:1056 Reference genes, whose expression is assumed to suffer minimal changes regardless the cell morphology, the stage of the cell cycle or the presence of harsh extracellular conditions are commonly used as controls in Northern blotting assays, microarrays, and semi-quantitative or quantitative RT-PCR. 28919888 5 80 theme Reference 877:885 arg1 genes 887:891 Reference genes 877:891 Reference genes 877:891 Reference genes, whose expression is assumed to suffer minimal changes regardless the cell morphology, the stage of the cell cycle or the presence of harsh extracellular conditions are commonly used as controls in Northern blotting assays, microarrays, and semi-quantitative or quantitative RT-PCR. 28919888 7 81 theme factor 1553:1558 arg1 1A 1560:1561 elongation factor 1A 1542:1561 elongation factor 1A 1542:1561 Here, we compared the transcriptional stability of the genes encoding for elongation factor 1A, Tfc1, a protein involved in transcription initiation on Pol III promoters, ribosomal protein L6, histone H2A, β-actin, β-tubulin, glyceraldehyde 3-phosphate dehydrogenase, UAF30, the upstream activating factor 30, and the transcription initiation factor TFIID subunit 10, during the fungal growth in different culture media and cell morphologies. 28919888 0 82 theme Constitutive 72:83 arg1 Expression 96:105 Constitutive and Stable Expression 72:105 Constitutive and Stable Expression 72:105 The Sporothrix schenckii Gene Encoding for the Ribosomal Protein L6 Has Constitutive and Stable Expression and Works as an Endogenous Control in Gene Expression Analysis. 28919888 2 83 from progress 432:439 arg1 aspects 454:460 molecular aspects 444:460 molecular aspects 444:460 The interest in basic and clinical features of this organism has significantly increased in the last years, yet little progress in molecular aspects has been reported. 28919888 0 84 theme Stable 89:94 arg1 Expression 96:105 Constitutive and Stable Expression 72:105 Constitutive and Stable Expression 72:105 The Sporothrix schenckii Gene Encoding for the Ribosomal Protein L6 Has Constitutive and Stable Expression and Works as an Endogenous Control in Gene Expression Analysis. 28919888 7 85 theme genes 1523:1527 arg1 stability 1506:1514 the transcriptional stability 1486:1514 the transcriptional stability of the genes encoding for elongation factor 1A, Tfc1, a protein involved in transcription initiation on Pol III promoters, ribosomal protein L6, histone H2A, β-actin, β-tubulin, glyceraldehyde 3-phosphate dehydrogenase, UAF30, the upstream activating factor 30, and the transcription initiation factor TFIID subunit 10 1486:1833 Here, we compared the transcriptional stability of the genes encoding for elongation factor 1A, Tfc1, a protein involved in transcription initiation on Pol III promoters, ribosomal protein L6, histone H2A, β-actin, β-tubulin, glyceraldehyde 3-phosphate dehydrogenase, UAF30, the upstream activating factor 30, and the transcription initiation factor TFIID subunit 10, during the fungal growth in different culture media and cell morphologies. 28919888 4 86 theme quantitative 733:744 arg1 methodologies 746:758 the quantitative methodologies 729:758 the quantitative methodologies used nowadays 729:772 Most of the quantitative methodologies used nowadays require data normalization, and this is achieved measuring the expression of endogenous control genes. 28919888 3 87 from changes 575:581 arg1 environment 604:614 the extracellular environment 586:614 the extracellular environment 586:614 Gene expression analysis is a set of powerful tools that helps to assess the cell response to changes in the extracellular environment, the genetic networks controlling metabolic pathways, and the adaptation to different growth conditions. 28919888 3 87 from changes 575:581 arg1 adaptation 678:687 the adaptation 674:687 the adaptation to different growth conditions 674:718 Gene expression analysis is a set of powerful tools that helps to assess the cell response to changes in the extracellular environment, the genetic networks controlling metabolic pathways, and the adaptation to different growth conditions. 28919888 3 87 from changes 575:581 arg1 networks 629:636 the genetic networks 617:636 the genetic networks controlling metabolic pathways 617:667 Gene expression analysis is a set of powerful tools that helps to assess the cell response to changes in the extracellular environment, the genetic networks controlling metabolic pathways, and the adaptation to different growth conditions. 28919888 7 88 theme culture 1874:1880 arg1 media 1882:1886 different culture media 1864:1886 different culture media 1864:1886 Here, we compared the transcriptional stability of the genes encoding for elongation factor 1A, Tfc1, a protein involved in transcription initiation on Pol III promoters, ribosomal protein L6, histone H2A, β-actin, β-tubulin, glyceraldehyde 3-phosphate dehydrogenase, UAF30, the upstream activating factor 30, and the transcription initiation factor TFIID subunit 10, during the fungal growth in different culture media and cell morphologies. 28919888 8 89 theme constant 2010:2017 arg1 expression 2019:2028 a stable and constant expression 1997:2028 a stable and constant expression 1997:2028 Our results indicated that only the gene encoding for the ribosomal protein L6 showed a stable and constant expression. 28919888 6 90 theme taxonomic 1414:1422 arg1 classification 1424:1437 the taxonomic classification 1410:1437 the taxonomic classification of the organism under study 1410:1465 Since the biology of the organisms is usually species specific, it is difficult to find a reliable group of universal genes that can be used as controls for data normalization in experiments addressing the gene expression, regardless the taxonomic classification of the organism under study. 28919888 6 90 theme taxonomic 1414:1422 arg1 expression 1387:1396 the gene expression 1378:1396 the gene expression 1378:1396 Since the biology of the organisms is usually species specific, it is difficult to find a reliable group of universal genes that can be used as controls for data normalization in experiments addressing the gene expression, regardless the taxonomic classification of the organism under study. 28919888 5 91 theme Northern 1091:1098 arg1 blotting 1100:1107 Northern blotting 1091:1107 Northern blotting assays 1091:1114 Reference genes, whose expression is assumed to suffer minimal changes regardless the cell morphology, the stage of the cell cycle or the presence of harsh extracellular conditions are commonly used as controls in Northern blotting assays, microarrays, and semi-quantitative or quantitative RT-PCR. 28919888 7 92 from initiation 1606:1615 arg1 promoters 1628:1636 Pol III promoters 1620:1636 Pol III promoters 1620:1636 Here, we compared the transcriptional stability of the genes encoding for elongation factor 1A, Tfc1, a protein involved in transcription initiation on Pol III promoters, ribosomal protein L6, histone H2A, β-actin, β-tubulin, glyceraldehyde 3-phosphate dehydrogenase, UAF30, the upstream activating factor 30, and the transcription initiation factor TFIID subunit 10, during the fungal growth in different culture media and cell morphologies. 28919888 7 93 theme protein 1649:1655 arg1 protein 1572:1578 a protein 1570:1578 a protein involved in transcription initiation on Pol III promoters 1570:1636 Here, we compared the transcriptional stability of the genes encoding for elongation factor 1A, Tfc1, a protein involved in transcription initiation on Pol III promoters, ribosomal protein L6, histone H2A, β-actin, β-tubulin, glyceraldehyde 3-phosphate dehydrogenase, UAF30, the upstream activating factor 30, and the transcription initiation factor TFIID subunit 10, during the fungal growth in different culture media and cell morphologies. 28919888 7 93 theme protein 1649:1655 arg1 β-tubulin 1683:1691 β-tubulin 1683:1691 β-tubulin 1683:1691 Here, we compared the transcriptional stability of the genes encoding for elongation factor 1A, Tfc1, a protein involved in transcription initiation on Pol III promoters, ribosomal protein L6, histone H2A, β-actin, β-tubulin, glyceraldehyde 3-phosphate dehydrogenase, UAF30, the upstream activating factor 30, and the transcription initiation factor TFIID subunit 10, during the fungal growth in different culture media and cell morphologies. 28919888 7 93 theme protein 1649:1655 arg1 H2A 1669:1671 histone H2A 1661:1671 histone H2A 1661:1671 Here, we compared the transcriptional stability of the genes encoding for elongation factor 1A, Tfc1, a protein involved in transcription initiation on Pol III promoters, ribosomal protein L6, histone H2A, β-actin, β-tubulin, glyceraldehyde 3-phosphate dehydrogenase, UAF30, the upstream activating factor 30, and the transcription initiation factor TFIID subunit 10, during the fungal growth in different culture media and cell morphologies. 28919888 7 93 theme protein 1649:1655 arg1 β-actin 1674:1680 β-actin 1674:1680 β-actin 1674:1680 Here, we compared the transcriptional stability of the genes encoding for elongation factor 1A, Tfc1, a protein involved in transcription initiation on Pol III promoters, ribosomal protein L6, histone H2A, β-actin, β-tubulin, glyceraldehyde 3-phosphate dehydrogenase, UAF30, the upstream activating factor 30, and the transcription initiation factor TFIID subunit 10, during the fungal growth in different culture media and cell morphologies. 28919888 7 93 theme protein 1649:1655 arg1 dehydrogenase 1721:1733 glyceraldehyde 3-phosphate dehydrogenase 1694:1733 glyceraldehyde 3-phosphate dehydrogenase 1694:1733 Here, we compared the transcriptional stability of the genes encoding for elongation factor 1A, Tfc1, a protein involved in transcription initiation on Pol III promoters, ribosomal protein L6, histone H2A, β-actin, β-tubulin, glyceraldehyde 3-phosphate dehydrogenase, UAF30, the upstream activating factor 30, and the transcription initiation factor TFIID subunit 10, during the fungal growth in different culture media and cell morphologies. 28919888 7 93 theme protein 1649:1655 arg1 factor 1767:1772 the upstream activating factor 30 1743:1775 the upstream activating factor 30 1743:1775 Here, we compared the transcriptional stability of the genes encoding for elongation factor 1A, Tfc1, a protein involved in transcription initiation on Pol III promoters, ribosomal protein L6, histone H2A, β-actin, β-tubulin, glyceraldehyde 3-phosphate dehydrogenase, UAF30, the upstream activating factor 30, and the transcription initiation factor TFIID subunit 10, during the fungal growth in different culture media and cell morphologies. 28919888 7 93 theme protein 1649:1655 arg1 UAF30 1736:1740 UAF30 1736:1740 UAF30 1736:1740 Here, we compared the transcriptional stability of the genes encoding for elongation factor 1A, Tfc1, a protein involved in transcription initiation on Pol III promoters, ribosomal protein L6, histone H2A, β-actin, β-tubulin, glyceraldehyde 3-phosphate dehydrogenase, UAF30, the upstream activating factor 30, and the transcription initiation factor TFIID subunit 10, during the fungal growth in different culture media and cell morphologies. 28919888 7 93 theme protein 1649:1655 arg1 L6 1657:1658 ribosomal protein L6 1639:1658 ribosomal protein L6 1639:1658 Here, we compared the transcriptional stability of the genes encoding for elongation factor 1A, Tfc1, a protein involved in transcription initiation on Pol III promoters, ribosomal protein L6, histone H2A, β-actin, β-tubulin, glyceraldehyde 3-phosphate dehydrogenase, UAF30, the upstream activating factor 30, and the transcription initiation factor TFIID subunit 10, during the fungal growth in different culture media and cell morphologies. 28919888 2 94 theme little 425:430 arg1 progress 432:439 little progress 425:439 little progress in molecular aspects 425:460 The interest in basic and clinical features of this organism has significantly increased in the last years, yet little progress in molecular aspects has been reported. 28919888 2 95 theme organism 365:372 arg1 features 348:355 basic and clinical features 329:355 basic and clinical features of this organism 329:372 The interest in basic and clinical features of this organism has significantly increased in the last years, yet little progress in molecular aspects has been reported. 28919888 8 96 theme protein 1979:1985 arg1 L6 1987:1988 the ribosomal protein L6 1965:1988 the ribosomal protein L6 1965:1988 Our results indicated that only the gene encoding for the ribosomal protein L6 showed a stable and constant expression. 28919888 7 97 theme fungal 1847:1852 arg1 growth 1854:1859 the fungal growth 1843:1859 the fungal growth in different culture media and cell morphologies 1843:1908 Here, we compared the transcriptional stability of the genes encoding for elongation factor 1A, Tfc1, a protein involved in transcription initiation on Pol III promoters, ribosomal protein L6, histone H2A, β-actin, β-tubulin, glyceraldehyde 3-phosphate dehydrogenase, UAF30, the upstream activating factor 30, and the transcription initiation factor TFIID subunit 10, during the fungal growth in different culture media and cell morphologies. 28919888 2 98 theme last 409:412 arg1 years 414:418 the last years 405:418 the last years 405:418 The interest in basic and clinical features of this organism has significantly increased in the last years, yet little progress in molecular aspects has been reported. 28919888 5 99 theme cell 997:1000 arg1 cycle 1002:1006 the cell cycle 993:1006 the cell cycle 993:1006 Reference genes, whose expression is assumed to suffer minimal changes regardless the cell morphology, the stage of the cell cycle or the presence of harsh extracellular conditions are commonly used as controls in Northern blotting assays, microarrays, and semi-quantitative or quantitative RT-PCR. 28919888 0 100 theme Ribosomal 47:55 arg1 L6 65:66 the Ribosomal Protein L6 43:66 the Ribosomal Protein L6 43:66 The Sporothrix schenckii Gene Encoding for the Ribosomal Protein L6 Has Constitutive and Stable Expression and Works as an Endogenous Control in Gene Expression Analysis. 28919888 7 101 theme factor 1811:1816 arg1 subunit 1824:1830 the transcription initiation factor TFIID subunit 10 1782:1833 the transcription initiation factor TFIID subunit 10 1782:1833 Here, we compared the transcriptional stability of the genes encoding for elongation factor 1A, Tfc1, a protein involved in transcription initiation on Pol III promoters, ribosomal protein L6, histone H2A, β-actin, β-tubulin, glyceraldehyde 3-phosphate dehydrogenase, UAF30, the upstream activating factor 30, and the transcription initiation factor TFIID subunit 10, during the fungal growth in different culture media and cell morphologies. 28919888 3 102 theme metabolic 650:658 arg1 pathways 660:667 metabolic pathways 650:667 metabolic pathways 650:667 Gene expression analysis is a set of powerful tools that helps to assess the cell response to changes in the extracellular environment, the genetic networks controlling metabolic pathways, and the adaptation to different growth conditions. 28919888 3 103 theme Gene 481:484 arg1 analysis 497:504 Gene expression analysis 481:504 Gene expression analysis 481:504 Gene expression analysis is a set of powerful tools that helps to assess the cell response to changes in the extracellular environment, the genetic networks controlling metabolic pathways, and the adaptation to different growth conditions. 28919888 3 103 theme Gene 481:484 arg1 set 511:513 a set 509:513 a set of powerful tools that helps to assess the cell response to changes in the extracellular environment, the genetic networks controlling metabolic pathways, and the adaptation to different growth conditions 509:718 Gene expression analysis is a set of powerful tools that helps to assess the cell response to changes in the extracellular environment, the genetic networks controlling metabolic pathways, and the adaptation to different growth conditions. 28919888 3 103 theme Gene 481:484 arg1 tools 527:531 powerful tools 518:531 powerful tools 518:531 Gene expression analysis is a set of powerful tools that helps to assess the cell response to changes in the extracellular environment, the genetic networks controlling metabolic pathways, and the adaptation to different growth conditions. 28919888 7 104 theme TFIID 1818:1822 arg1 subunit 1824:1830 the transcription initiation factor TFIID subunit 10 1782:1833 the transcription initiation factor TFIID subunit 10 1782:1833 Here, we compared the transcriptional stability of the genes encoding for elongation factor 1A, Tfc1, a protein involved in transcription initiation on Pol III promoters, ribosomal protein L6, histone H2A, β-actin, β-tubulin, glyceraldehyde 3-phosphate dehydrogenase, UAF30, the upstream activating factor 30, and the transcription initiation factor TFIID subunit 10, during the fungal growth in different culture media and cell morphologies. 28919888 7 105 theme transcription 1786:1798 arg1 subunit 1824:1830 the transcription initiation factor TFIID subunit 10 1782:1833 the transcription initiation factor TFIID subunit 10 1782:1833 Here, we compared the transcriptional stability of the genes encoding for elongation factor 1A, Tfc1, a protein involved in transcription initiation on Pol III promoters, ribosomal protein L6, histone H2A, β-actin, β-tubulin, glyceraldehyde 3-phosphate dehydrogenase, UAF30, the upstream activating factor 30, and the transcription initiation factor TFIID subunit 10, during the fungal growth in different culture media and cell morphologies. 28919888 0 106 contain Has 68:70 arg1 Gene 25:28 The Sporothrix schenckii Gene 0:28 The Sporothrix schenckii Gene Encoding for the Ribosomal Protein L6 0:66 The Sporothrix schenckii Gene Encoding for the Ribosomal Protein L6 Has Constitutive and Stable Expression and Works as an Endogenous Control in Gene Expression Analysis. 28919888 0 106 contain Has 68:70 arg2 Expression 96:105 Constitutive and Stable Expression 72:105 Constitutive and Stable Expression 72:105 The Sporothrix schenckii Gene Encoding for the Ribosomal Protein L6 Has Constitutive and Stable Expression and Works as an Endogenous Control in Gene Expression Analysis. 28919888 1 107 theme agents 216:221 arg1 one 195:197 one 195:197 one 195:197 Sporothrix schenckii is one of the causative agents of sporotrichosis, a worldwide-distributed mycosis that affects humans and other mammals. 28919888 1 107 theme agents 216:221 arg1 agents 216:221 the causative agents 202:221 the causative agents of sporotrichosis, a worldwide-distributed mycosis that affects humans and other mammals 202:310 Sporothrix schenckii is one of the causative agents of sporotrichosis, a worldwide-distributed mycosis that affects humans and other mammals. 28919888 6 108 theme organism 1446:1453 arg1 classification 1424:1437 the taxonomic classification 1410:1437 the taxonomic classification of the organism under study 1410:1465 Since the biology of the organisms is usually species specific, it is difficult to find a reliable group of universal genes that can be used as controls for data normalization in experiments addressing the gene expression, regardless the taxonomic classification of the organism under study. 28919888 6 108 theme organism 1446:1453 arg1 expression 1387:1396 the gene expression 1378:1396 the gene expression 1378:1396 Since the biology of the organisms is usually species specific, it is difficult to find a reliable group of universal genes that can be used as controls for data normalization in experiments addressing the gene expression, regardless the taxonomic classification of the organism under study. 28919888 1 109 theme sporotrichosis 226:239 arg1 agents 216:221 the causative agents 202:221 the causative agents of sporotrichosis, a worldwide-distributed mycosis that affects humans and other mammals 202:310 Sporothrix schenckii is one of the causative agents of sporotrichosis, a worldwide-distributed mycosis that affects humans and other mammals. 28829594 0 0 theme B-Lymphoma 74:83 arg1 Cells 85:89 B-Lymphoma Cells 74:89 B-Lymphoma Cells 74:89 CD22 Ligands on a Natural N-Glycan Scaffold Efficiently Deliver Toxins to B-Lymphoma Cells. 28829594 5 1 theme lymphoma 946:953 arg1 cells 955:959 B-cell lymphoma cells 939:959 B-cell lymphoma cells 939:959 Conjugates of these multivalent ligands with auristatin and saporin toxins are efficiently internalized via hCD22 resulting in killing of B-cell lymphoma cells. 28829594 0 2 from Ligands 5:11 arg1 Scaffold 35:42 a Natural N-Glycan Scaffold 16:42 a Natural N-Glycan Scaffold 16:42 CD22 Ligands on a Natural N-Glycan Scaffold Efficiently Deliver Toxins to B-Lymphoma Cells. 28829594 3 3 theme high 493:496 arg1 ligands 519:525 high affinity CD22 glycan ligands 493:525 high affinity CD22 glycan ligands 493:525 We describe here a chemically defined natural N-linked glycan scaffold that displays high affinity CD22 glycan ligands and outcompetes the natural ligand for the receptor, resulting in single molecule binding to CD22 and endocytosis into cells. 28829594 6 4 theme targeting 990:998 arg1 strategy 1000:1007 This single molecule ligand targeting strategy 962:1007 This single molecule ligand targeting strategy 962:1007 This single molecule ligand targeting strategy represents an alternative to antibody- and nanoparticle-mediated approaches for delivery of agents to cells expressing CD22 and other Siglecs. 28829594 5 5 theme cells 955:959 arg1 killing 928:934 killing 928:934 killing of B-cell lymphoma cells 928:959 Conjugates of these multivalent ligands with auristatin and saporin toxins are efficiently internalized via hCD22 resulting in killing of B-cell lymphoma cells. 28829594 4 6 theme monovalent 718:727 arg1 ligand 729:734 the monovalent ligand 714:734 the monovalent ligand 714:734 Binding affinity is increased by up to 1500-fold compared to the monovalent ligand, while maintaining the selectivity for hCD22 over other Siglecs. 28829594 1 7 theme validated 225:233 arg1 target 235:240 a validated target 223:240 a validated target for antibody and nanoparticle based therapeutics 223:289 CD22 is a sialic acid-binding immunoglobulin-like lectin (Siglec) that is highly expressed on B-cells and B cell lymphomas, and is a validated target for antibody and nanoparticle based therapeutics. 28829594 3 8 theme glycan 463:468 arg1 scaffold 470:477 a chemically defined natural N-linked glycan scaffold 425:477 a chemically defined natural N-linked glycan scaffold that displays high affinity CD22 glycan ligands and outcompetes the natural ligand for the receptor, resulting in single molecule binding to CD22 and endocytosis into cells 425:650 We describe here a chemically defined natural N-linked glycan scaffold that displays high affinity CD22 glycan ligands and outcompetes the natural ligand for the receptor, resulting in single molecule binding to CD22 and endocytosis into cells. 28829594 6 9 theme nanoparticle-mediated 1052:1072 arg1 approaches 1074:1083 antibody- and nanoparticle-mediated approaches 1038:1083 antibody- and nanoparticle-mediated approaches 1038:1083 This single molecule ligand targeting strategy represents an alternative to antibody- and nanoparticle-mediated approaches for delivery of agents to cells expressing CD22 and other Siglecs. 28829594 3 10 theme glycan 512:517 arg1 ligands 519:525 high affinity CD22 glycan ligands 493:525 high affinity CD22 glycan ligands 493:525 We describe here a chemically defined natural N-linked glycan scaffold that displays high affinity CD22 glycan ligands and outcompetes the natural ligand for the receptor, resulting in single molecule binding to CD22 and endocytosis into cells. 28829594 6 11 theme agents 1101:1106 arg1 delivery 1089:1096 delivery 1089:1096 delivery of agents to cells expressing CD22 and other Siglecs 1089:1149 This single molecule ligand targeting strategy represents an alternative to antibody- and nanoparticle-mediated approaches for delivery of agents to cells expressing CD22 and other Siglecs. 28829594 6 12 theme molecule 974:981 arg1 strategy 1000:1007 This single molecule ligand targeting strategy 962:1007 This single molecule ligand targeting strategy 962:1007 This single molecule ligand targeting strategy represents an alternative to antibody- and nanoparticle-mediated approaches for delivery of agents to cells expressing CD22 and other Siglecs. 28829594 6 13 theme other 1137:1141 arg1 Siglecs 1143:1149 other Siglecs 1137:1149 other Siglecs 1137:1149 This single molecule ligand targeting strategy represents an alternative to antibody- and nanoparticle-mediated approaches for delivery of agents to cells expressing CD22 and other Siglecs. 28829594 6 14 theme antibody- 1038:1046 arg1 approaches 1074:1083 antibody- and nanoparticle-mediated approaches 1038:1083 antibody- and nanoparticle-mediated approaches 1038:1083 This single molecule ligand targeting strategy represents an alternative to antibody- and nanoparticle-mediated approaches for delivery of agents to cells expressing CD22 and other Siglecs. 28829594 4 15 theme Binding 653:659 arg1 affinity 661:668 Binding affinity 653:668 Binding affinity 653:668 Binding affinity is increased by up to 1500-fold compared to the monovalent ligand, while maintaining the selectivity for hCD22 over other Siglecs. 28829594 0 16 theme CD22 0:3 arg1 Ligands 5:11 CD22 Ligands 0:11 CD22 Ligands on a Natural N-Glycan Scaffold 0:42 CD22 Ligands on a Natural N-Glycan Scaffold Efficiently Deliver Toxins to B-Lymphoma Cells. 28829594 6 17 theme single 967:972 arg1 strategy 1000:1007 This single molecule ligand targeting strategy 962:1007 This single molecule ligand targeting strategy 962:1007 This single molecule ligand targeting strategy represents an alternative to antibody- and nanoparticle-mediated approaches for delivery of agents to cells expressing CD22 and other Siglecs. 28829594 4 18 dep 1500-fold 692:700 arg1 to 689:690 to 689:690 to 689:690 Binding affinity is increased by up to 1500-fold compared to the monovalent ligand, while maintaining the selectivity for hCD22 over other Siglecs. 28829594 1 19 theme antibody 246:253 arg1 therapeutics 278:289 antibody and nanoparticle based therapeutics 246:289 therapeutics 278:289 CD22 is a sialic acid-binding immunoglobulin-like lectin (Siglec) that is highly expressed on B-cells and B cell lymphomas, and is a validated target for antibody and nanoparticle based therapeutics. 28829594 5 20 theme B-cell 939:944 arg1 cells 955:959 B-cell lymphoma cells 939:959 B-cell lymphoma cells 939:959 Conjugates of these multivalent ligands with auristatin and saporin toxins are efficiently internalized via hCD22 resulting in killing of B-cell lymphoma cells. 28829594 3 21 theme defined 438:444 arg1 scaffold 470:477 a chemically defined natural N-linked glycan scaffold 425:477 a chemically defined natural N-linked glycan scaffold that displays high affinity CD22 glycan ligands and outcompetes the natural ligand for the receptor, resulting in single molecule binding to CD22 and endocytosis into cells 425:650 We describe here a chemically defined natural N-linked glycan scaffold that displays high affinity CD22 glycan ligands and outcompetes the natural ligand for the receptor, resulting in single molecule binding to CD22 and endocytosis into cells. 28829594 5 22 with Conjugates 801:810 arg1 auristatin 846:855 auristatin 846:855 auristatin 846:855 Conjugates of these multivalent ligands with auristatin and saporin toxins are efficiently internalized via hCD22 resulting in killing of B-cell lymphoma cells. 28829594 5 22 with Conjugates 801:810 arg1 saporin 861:867 saporin 861:867 saporin 861:867 Conjugates of these multivalent ligands with auristatin and saporin toxins are efficiently internalized via hCD22 resulting in killing of B-cell lymphoma cells. 28829594 3 23 theme natural 547:553 arg1 ligand 555:560 the natural ligand 543:560 the natural ligand for the receptor 543:577 We describe here a chemically defined natural N-linked glycan scaffold that displays high affinity CD22 glycan ligands and outcompetes the natural ligand for the receptor, resulting in single molecule binding to CD22 and endocytosis into cells. 28829594 3 24 theme natural 446:452 arg1 scaffold 470:477 a chemically defined natural N-linked glycan scaffold 425:477 a chemically defined natural N-linked glycan scaffold that displays high affinity CD22 glycan ligands and outcompetes the natural ligand for the receptor, resulting in single molecule binding to CD22 and endocytosis into cells 425:650 We describe here a chemically defined natural N-linked glycan scaffold that displays high affinity CD22 glycan ligands and outcompetes the natural ligand for the receptor, resulting in single molecule binding to CD22 and endocytosis into cells. 28829594 0 25 theme N-Glycan 26:33 arg1 Scaffold 35:42 a Natural N-Glycan Scaffold 16:42 a Natural N-Glycan Scaffold 16:42 CD22 Ligands on a Natural N-Glycan Scaffold Efficiently Deliver Toxins to B-Lymphoma Cells. 28829594 1 26 theme nanoparticle 259:270 arg1 therapeutics 278:289 antibody and nanoparticle based therapeutics 246:289 therapeutics 278:289 CD22 is a sialic acid-binding immunoglobulin-like lectin (Siglec) that is highly expressed on B-cells and B cell lymphomas, and is a validated target for antibody and nanoparticle based therapeutics. 28829594 5 27 theme multivalent 821:831 arg1 ligands 833:839 these multivalent ligands 815:839 these multivalent ligands 815:839 Conjugates of these multivalent ligands with auristatin and saporin toxins are efficiently internalized via hCD22 resulting in killing of B-cell lymphoma cells. 28829594 0 28 theme Natural 18:24 arg1 Scaffold 35:42 a Natural N-Glycan Scaffold 16:42 a Natural N-Glycan Scaffold 16:42 CD22 Ligands on a Natural N-Glycan Scaffold Efficiently Deliver Toxins to B-Lymphoma Cells. 28829594 1 29 theme based 272:276 arg1 therapeutics 278:289 antibody and nanoparticle based therapeutics 246:289 therapeutics 278:289 CD22 is a sialic acid-binding immunoglobulin-like lectin (Siglec) that is highly expressed on B-cells and B cell lymphomas, and is a validated target for antibody and nanoparticle based therapeutics. 28829594 4 30 theme other 786:790 arg1 Siglecs 792:798 other Siglecs 786:798 other Siglecs 786:798 Binding affinity is increased by up to 1500-fold compared to the monovalent ligand, while maintaining the selectivity for hCD22 over other Siglecs. 28829594 5 31 theme ligands 833:839 arg1 Conjugates 801:810 Conjugates 801:810 Conjugates of these multivalent ligands with auristatin and saporin toxins 801:874 Conjugates of these multivalent ligands with auristatin and saporin toxins are efficiently internalized via hCD22 resulting in killing of B-cell lymphoma cells. 28829594 1 32 theme B 198:198 arg1 lymphomas 205:213 B cell lymphomas 198:213 B cell lymphomas 198:213 CD22 is a sialic acid-binding immunoglobulin-like lectin (Siglec) that is highly expressed on B-cells and B cell lymphomas, and is a validated target for antibody and nanoparticle based therapeutics. 28829594 3 33 link N-linked 454:461 arg1 scaffold 470:477 a chemically defined natural N-linked glycan scaffold 425:477 a chemically defined natural N-linked glycan scaffold that displays high affinity CD22 glycan ligands and outcompetes the natural ligand for the receptor, resulting in single molecule binding to CD22 and endocytosis into cells 425:650 We describe here a chemically defined natural N-linked glycan scaffold that displays high affinity CD22 glycan ligands and outcompetes the natural ligand for the receptor, resulting in single molecule binding to CD22 and endocytosis into cells. 28829594 2 34 from complexity 349:358 arg1 production 396:405 production 396:405 production 396:405 However, cell targeted therapeutics are limited by their complexity, heterogeneity, and difficulties in production. 28829594 3 35 theme N-linked 454:461 arg1 scaffold 470:477 a chemically defined natural N-linked glycan scaffold 425:477 a chemically defined natural N-linked glycan scaffold that displays high affinity CD22 glycan ligands and outcompetes the natural ligand for the receptor, resulting in single molecule binding to CD22 and endocytosis into cells 425:650 We describe here a chemically defined natural N-linked glycan scaffold that displays high affinity CD22 glycan ligands and outcompetes the natural ligand for the receptor, resulting in single molecule binding to CD22 and endocytosis into cells. 28829594 5 36 dep auristatin 846:855 arg1 toxins 869:874 toxins 869:874 toxins 869:874 Conjugates of these multivalent ligands with auristatin and saporin toxins are efficiently internalized via hCD22 resulting in killing of B-cell lymphoma cells. 28829594 1 37 theme sialic 102:107 arg1 CD22 92:95 CD22 92:95 CD22 92:95 CD22 is a sialic acid-binding immunoglobulin-like lectin (Siglec) that is highly expressed on B-cells and B cell lymphomas, and is a validated target for antibody and nanoparticle based therapeutics. 28829594 1 37 theme sialic 102:107 arg1 Siglec 150:155 Siglec 150:155 Siglec 150:155 CD22 is a sialic acid-binding immunoglobulin-like lectin (Siglec) that is highly expressed on B-cells and B cell lymphomas, and is a validated target for antibody and nanoparticle based therapeutics. 28829594 1 37 theme sialic 102:107 arg1 lectin 142:147 a sialic acid-binding immunoglobulin-like lectin 100:147 a sialic acid-binding immunoglobulin-like lectin (Siglec) that is highly expressed on B-cells and B cell lymphomas, and is a validated target for antibody and nanoparticle based therapeutics 100:289 CD22 is a sialic acid-binding immunoglobulin-like lectin (Siglec) that is highly expressed on B-cells and B cell lymphomas, and is a validated target for antibody and nanoparticle based therapeutics. 28829594 2 38 from heterogeneity 361:373 arg1 production 396:405 production 396:405 production 396:405 However, cell targeted therapeutics are limited by their complexity, heterogeneity, and difficulties in production. 28829594 1 39 theme acid-binding 109:120 arg1 CD22 92:95 CD22 92:95 CD22 92:95 CD22 is a sialic acid-binding immunoglobulin-like lectin (Siglec) that is highly expressed on B-cells and B cell lymphomas, and is a validated target for antibody and nanoparticle based therapeutics. 28829594 1 39 theme acid-binding 109:120 arg1 Siglec 150:155 Siglec 150:155 Siglec 150:155 CD22 is a sialic acid-binding immunoglobulin-like lectin (Siglec) that is highly expressed on B-cells and B cell lymphomas, and is a validated target for antibody and nanoparticle based therapeutics. 28829594 1 39 theme acid-binding 109:120 arg1 lectin 142:147 a sialic acid-binding immunoglobulin-like lectin 100:147 a sialic acid-binding immunoglobulin-like lectin (Siglec) that is highly expressed on B-cells and B cell lymphomas, and is a validated target for antibody and nanoparticle based therapeutics 100:289 CD22 is a sialic acid-binding immunoglobulin-like lectin (Siglec) that is highly expressed on B-cells and B cell lymphomas, and is a validated target for antibody and nanoparticle based therapeutics. 28829594 1 40 theme cell 200:203 arg1 lymphomas 205:213 B cell lymphomas 198:213 B cell lymphomas 198:213 CD22 is a sialic acid-binding immunoglobulin-like lectin (Siglec) that is highly expressed on B-cells and B cell lymphomas, and is a validated target for antibody and nanoparticle based therapeutics. 28829594 2 41 from difficulties 380:391 arg1 production 396:405 production 396:405 production 396:405 However, cell targeted therapeutics are limited by their complexity, heterogeneity, and difficulties in production. 28829594 1 42 theme immunoglobulin-like 122:140 arg1 CD22 92:95 CD22 92:95 CD22 92:95 CD22 is a sialic acid-binding immunoglobulin-like lectin (Siglec) that is highly expressed on B-cells and B cell lymphomas, and is a validated target for antibody and nanoparticle based therapeutics. 28829594 1 42 theme immunoglobulin-like 122:140 arg1 Siglec 150:155 Siglec 150:155 Siglec 150:155 CD22 is a sialic acid-binding immunoglobulin-like lectin (Siglec) that is highly expressed on B-cells and B cell lymphomas, and is a validated target for antibody and nanoparticle based therapeutics. 28829594 1 42 theme immunoglobulin-like 122:140 arg1 lectin 142:147 a sialic acid-binding immunoglobulin-like lectin 100:147 a sialic acid-binding immunoglobulin-like lectin (Siglec) that is highly expressed on B-cells and B cell lymphomas, and is a validated target for antibody and nanoparticle based therapeutics 100:289 CD22 is a sialic acid-binding immunoglobulin-like lectin (Siglec) that is highly expressed on B-cells and B cell lymphomas, and is a validated target for antibody and nanoparticle based therapeutics. 28829594 2 43 theme cell 301:304 arg1 therapeutics 315:326 cell targeted therapeutics 301:326 cell targeted therapeutics 301:326 However, cell targeted therapeutics are limited by their complexity, heterogeneity, and difficulties in production. 28829594 2 44 theme targeted 306:313 arg1 therapeutics 315:326 cell targeted therapeutics 301:326 cell targeted therapeutics 301:326 However, cell targeted therapeutics are limited by their complexity, heterogeneity, and difficulties in production. 28829594 3 45 theme affinity 498:505 arg1 ligands 519:525 high affinity CD22 glycan ligands 493:525 high affinity CD22 glycan ligands 493:525 We describe here a chemically defined natural N-linked glycan scaffold that displays high affinity CD22 glycan ligands and outcompetes the natural ligand for the receptor, resulting in single molecule binding to CD22 and endocytosis into cells. 28829594 6 46 theme ligand 983:988 arg1 strategy 1000:1007 This single molecule ligand targeting strategy 962:1007 This single molecule ligand targeting strategy 962:1007 This single molecule ligand targeting strategy represents an alternative to antibody- and nanoparticle-mediated approaches for delivery of agents to cells expressing CD22 and other Siglecs. 28829594 3 47 theme single 593:598 arg1 molecule 600:607 single molecule 593:607 single molecule binding to CD22 and endocytosis into cells 593:650 We describe here a chemically defined natural N-linked glycan scaffold that displays high affinity CD22 glycan ligands and outcompetes the natural ligand for the receptor, resulting in single molecule binding to CD22 and endocytosis into cells. 28829594 3 48 theme CD22 507:510 arg1 ligands 519:525 high affinity CD22 glycan ligands 493:525 high affinity CD22 glycan ligands 493:525 We describe here a chemically defined natural N-linked glycan scaffold that displays high affinity CD22 glycan ligands and outcompetes the natural ligand for the receptor, resulting in single molecule binding to CD22 and endocytosis into cells. 28710744 0 0 theme flavus 88:93 arg1 F3 103:104 F3 103:104 F3 103:104 Cloning and characterization of F3PYC gene encoding pyruvate carboxylase in Aspergillus flavus strain (F3). 28710744 0 0 theme flavus 88:93 arg1 strain 95:100 Aspergillus flavus strain 76:100 Aspergillus flavus strain (F3) 76:105 Cloning and characterization of F3PYC gene encoding pyruvate carboxylase in Aspergillus flavus strain (F3). 28710744 5 1 theme % 698:698 arg1 similarity 700:709 90-95% similarity 693:709 90-95% similarity to those deduced from PYC gene from different fungal strains including; Aspergillus parasiticus, Neosartorya fischeri, Aspergillus fumigatus, Aspergillus clavatus, and Aspergillus niger 693:895 Deduced protein showed 90-95% similarity to those deduced from PYC gene from different fungal strains including; Aspergillus parasiticus, Neosartorya fischeri, Aspergillus fumigatus, Aspergillus clavatus, and Aspergillus niger. 28710744 7 2 theme most 1048:1051 arg1 sites 1078:1082 most possible N-glycosylation sites 1048:1082 most possible N-glycosylation sites 1048:1082 Amongst most possible N-glycosylation sites were -N-S-S-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, N-G-S-S- at 517 amino acid, and N-T-S-R- at 1111 amino acid, with several functions have been proposed for the carbohydrate moiety such as thermal stability, pH, and temperature optima for activity and stabilization of the three-dimensional structure. 28710744 6 3 gly glycosylation 993:1005 arg2 sites 1007:1011 four potential N-linked glycosylation sites 969:1011 four potential N-linked glycosylation sites 969:1011 Protein generated from the PYC gene was a homotetramer (α4) and having four potential N-linked glycosylation sites and had no signal peptide. 28710744 6 3 gly glycosylation 993:1005 arg2 four 969:972 four 969:972 four 969:972 Protein generated from the PYC gene was a homotetramer (α4) and having four potential N-linked glycosylation sites and had no signal peptide. 28710744 3 4 theme resistant 442:450 arg1 F3 498:499 F3 498:499 F3 498:499 In this study, gene walking method was used to clone and characterize pyruvate carboxylase gene (F3PYC) from heavy metal resistant indigenous fungal isolate Aspergillus flavus (F3). 28710744 3 4 theme resistant 442:450 arg1 flavus 490:495 heavy metal resistant indigenous fungal isolate Aspergillus flavus 430:495 heavy metal resistant indigenous fungal isolate Aspergillus flavus (F3) 430:500 In this study, gene walking method was used to clone and characterize pyruvate carboxylase gene (F3PYC) from heavy metal resistant indigenous fungal isolate Aspergillus flavus (F3). 28710744 3 5 from flavus 490:495 arg1 gene 412:415 pyruvate carboxylase gene 391:415 pyruvate carboxylase gene (F3PYC) from heavy metal resistant indigenous fungal isolate Aspergillus flavus (F3) 391:500 In this study, gene walking method was used to clone and characterize pyruvate carboxylase gene (F3PYC) from heavy metal resistant indigenous fungal isolate Aspergillus flavus (F3). 28710744 3 5 from flavus 490:495 arg1 F3PYC 418:422 F3PYC 418:422 F3PYC 418:422 In this study, gene walking method was used to clone and characterize pyruvate carboxylase gene (F3PYC) from heavy metal resistant indigenous fungal isolate Aspergillus flavus (F3). 28710744 4 6 theme open 517:520 arg1 frame 530:534 an open reading frame 514:534 an open reading frame which encodes 1193 amino acid protein (isoelectric point: 6.10) with a calculated molecular weight of 131.2008 kDa 514:649 3579 bp of an open reading frame which encodes 1193 amino acid protein (isoelectric point: 6.10) with a calculated molecular weight of 131.2008 kDa was characterized. 28710744 4 6 theme open 517:520 arg1 protein 566:572 1193 amino acid protein 550:572 1193 amino acid protein (isoelectric point: 6.10) with a calculated molecular weight of 131.2008 kDa 550:649 3579 bp of an open reading frame which encodes 1193 amino acid protein (isoelectric point: 6.10) with a calculated molecular weight of 131.2008 kDa was characterized. 28710744 0 7 theme Aspergillus 76:86 arg1 F3 103:104 F3 103:104 F3 103:104 Cloning and characterization of F3PYC gene encoding pyruvate carboxylase in Aspergillus flavus strain (F3). 28710744 0 7 theme Aspergillus 76:86 arg1 strain 95:100 Aspergillus flavus strain 76:100 Aspergillus flavus strain (F3) 76:105 Cloning and characterization of F3PYC gene encoding pyruvate carboxylase in Aspergillus flavus strain (F3). 28710744 7 8 theme possible 1053:1060 arg1 sites 1078:1082 most possible N-glycosylation sites 1048:1082 most possible N-glycosylation sites 1048:1082 Amongst most possible N-glycosylation sites were -N-S-S-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, N-G-S-S- at 517 amino acid, and N-T-S-R- at 1111 amino acid, with several functions have been proposed for the carbohydrate moiety such as thermal stability, pH, and temperature optima for activity and stabilization of the three-dimensional structure. 28710744 7 9 from acid 1168:1171 arg1 -N-S-S-I- 1089:1097 -N-S-S-I- 1089:1097 -N-S-S-I- at 36 amino acid 1089:1114 Amongst most possible N-glycosylation sites were -N-S-S-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, N-G-S-S- at 517 amino acid, and N-T-S-R- at 1111 amino acid, with several functions have been proposed for the carbohydrate moiety such as thermal stability, pH, and temperature optima for activity and stabilization of the three-dimensional structure. 28710744 7 9 from acid 1168:1171 arg1 N-T-S-R- 1178:1185 N-T-S-R- 1178:1185 N-T-S-R- at 1111 amino acid 1178:1204 Amongst most possible N-glycosylation sites were -N-S-S-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, N-G-S-S- at 517 amino acid, and N-T-S-R- at 1111 amino acid, with several functions have been proposed for the carbohydrate moiety such as thermal stability, pH, and temperature optima for activity and stabilization of the three-dimensional structure. 28710744 7 9 from acid 1168:1171 arg1 -N-G-T-V- 1117:1125 -N-G-T-V- 1117:1125 -N-G-T-V- at 237 amino acid 1117:1143 Amongst most possible N-glycosylation sites were -N-S-S-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, N-G-S-S- at 517 amino acid, and N-T-S-R- at 1111 amino acid, with several functions have been proposed for the carbohydrate moiety such as thermal stability, pH, and temperature optima for activity and stabilization of the three-dimensional structure. 28710744 7 9 from acid 1168:1171 arg1 N-G-S-S- 1146:1153 N-G-S-S- 1146:1153 N-G-S-S- at 517 amino acid 1146:1171 Amongst most possible N-glycosylation sites were -N-S-S-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, N-G-S-S- at 517 amino acid, and N-T-S-R- at 1111 amino acid, with several functions have been proposed for the carbohydrate moiety such as thermal stability, pH, and temperature optima for activity and stabilization of the three-dimensional structure. 28710744 2 10 theme metals 313:318 arg1 remediation 292:302 biological remediation 281:302 biological remediation of heavy metals 281:318 These organic acids play very important role for biological remediation of heavy metals. 28710744 1 11 theme L-malic 218:224 arg1 acid 226:229 L-malic acid 218:229 L-malic acid 218:229 Pyruvate carboxylase is a major enzyme for biosynthesis of organic acids like; citric acid, fumeric acid, and L-malic acid. 28710744 8 12 from flavus 1435:1440 arg1 cloning 1405:1411 cloning 1405:1411 cloning of F3PYC gene from A. flavus 1405:1440 Hence, cloning of F3PYC gene from A. flavus has important biotechnological applications. 28710744 7 13 theme carbohydrate 1257:1268 arg1 moiety 1270:1275 the carbohydrate moiety 1253:1275 the carbohydrate moiety such as thermal stability, pH, and temperature optima for activity and stabilization of the three-dimensional structure 1253:1395 Amongst most possible N-glycosylation sites were -N-S-S-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, N-G-S-S- at 517 amino acid, and N-T-S-R- at 1111 amino acid, with several functions have been proposed for the carbohydrate moiety such as thermal stability, pH, and temperature optima for activity and stabilization of the three-dimensional structure. 28710744 6 14 link N-linked 984:991 arg1 sites 1007:1011 four potential N-linked glycosylation sites 969:1011 four potential N-linked glycosylation sites 969:1011 Protein generated from the PYC gene was a homotetramer (α4) and having four potential N-linked glycosylation sites and had no signal peptide. 28710744 4 15 theme frame 530:534 arg1 3579 bp 503:509 3579 bp 503:509 3579 bp of an open reading frame which encodes 1193 amino acid protein (isoelectric point: 6.10) with a calculated molecular weight of 131.2008 kDa 503:649 3579 bp of an open reading frame which encodes 1193 amino acid protein (isoelectric point: 6.10) with a calculated molecular weight of 131.2008 kDa was characterized. 28710744 8 16 contain has 1442:1444 arg2 applications 1473:1484 important biotechnological applications 1446:1484 important biotechnological applications 1446:1484 Hence, cloning of F3PYC gene from A. flavus has important biotechnological applications. 28710744 8 16 contain has 1442:1444 arg1 cloning 1405:1411 cloning 1405:1411 cloning of F3PYC gene from A. flavus 1405:1440 Hence, cloning of F3PYC gene from A. flavus has important biotechnological applications. 28710744 8 17 theme F3PYC 1416:1420 arg1 gene 1422:1425 F3PYC gene 1416:1425 F3PYC gene 1416:1425 Hence, cloning of F3PYC gene from A. flavus has important biotechnological applications. 28710744 4 18 theme molecular 618:626 arg1 weight 628:633 a calculated molecular weight 605:633 a calculated molecular weight of 131.2008 kDa 605:649 3579 bp of an open reading frame which encodes 1193 amino acid protein (isoelectric point: 6.10) with a calculated molecular weight of 131.2008 kDa was characterized. 28710744 4 19 theme reading 522:528 arg1 frame 530:534 an open reading frame 514:534 an open reading frame which encodes 1193 amino acid protein (isoelectric point: 6.10) with a calculated molecular weight of 131.2008 kDa 514:649 3579 bp of an open reading frame which encodes 1193 amino acid protein (isoelectric point: 6.10) with a calculated molecular weight of 131.2008 kDa was characterized. 28710744 4 19 theme reading 522:528 arg1 protein 566:572 1193 amino acid protein 550:572 1193 amino acid protein (isoelectric point: 6.10) with a calculated molecular weight of 131.2008 kDa 550:649 3579 bp of an open reading frame which encodes 1193 amino acid protein (isoelectric point: 6.10) with a calculated molecular weight of 131.2008 kDa was characterized. 28710744 4 20 theme calculated 607:616 arg1 weight 628:633 a calculated molecular weight 605:633 a calculated molecular weight of 131.2008 kDa 605:649 3579 bp of an open reading frame which encodes 1193 amino acid protein (isoelectric point: 6.10) with a calculated molecular weight of 131.2008 kDa was characterized. 28710744 3 21 theme heavy 430:434 arg1 F3 498:499 F3 498:499 F3 498:499 In this study, gene walking method was used to clone and characterize pyruvate carboxylase gene (F3PYC) from heavy metal resistant indigenous fungal isolate Aspergillus flavus (F3). 28710744 3 21 theme heavy 430:434 arg1 flavus 490:495 heavy metal resistant indigenous fungal isolate Aspergillus flavus 430:495 heavy metal resistant indigenous fungal isolate Aspergillus flavus (F3) 430:500 In this study, gene walking method was used to clone and characterize pyruvate carboxylase gene (F3PYC) from heavy metal resistant indigenous fungal isolate Aspergillus flavus (F3). 28710744 5 22 theme PYC 733:735 arg1 gene 737:740 PYC gene 733:740 PYC gene 733:740 Deduced protein showed 90-95% similarity to those deduced from PYC gene from different fungal strains including; Aspergillus parasiticus, Neosartorya fischeri, Aspergillus fumigatus, Aspergillus clavatus, and Aspergillus niger. 28710744 2 23 theme organic 238:244 arg1 acids 246:250 These organic acids 232:250 These organic acids 232:250 These organic acids play very important role for biological remediation of heavy metals. 28710744 6 24 theme glycosylation 993:1005 arg1 sites 1007:1011 four potential N-linked glycosylation sites 969:1011 four potential N-linked glycosylation sites 969:1011 Protein generated from the PYC gene was a homotetramer (α4) and having four potential N-linked glycosylation sites and had no signal peptide. 28710744 6 25 theme PYC 925:927 arg1 gene 929:932 the PYC gene 921:932 the PYC gene 921:932 Protein generated from the PYC gene was a homotetramer (α4) and having four potential N-linked glycosylation sites and had no signal peptide. 28710744 7 26 theme N-glycosylation 1062:1076 arg1 sites 1078:1082 most possible N-glycosylation sites 1048:1082 most possible N-glycosylation sites 1048:1082 Amongst most possible N-glycosylation sites were -N-S-S-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, N-G-S-S- at 517 amino acid, and N-T-S-R- at 1111 amino acid, with several functions have been proposed for the carbohydrate moiety such as thermal stability, pH, and temperature optima for activity and stabilization of the three-dimensional structure. 28710744 3 27 theme pyruvate 391:398 arg1 gene 412:415 pyruvate carboxylase gene 391:415 pyruvate carboxylase gene (F3PYC) from heavy metal resistant indigenous fungal isolate Aspergillus flavus (F3) 391:500 In this study, gene walking method was used to clone and characterize pyruvate carboxylase gene (F3PYC) from heavy metal resistant indigenous fungal isolate Aspergillus flavus (F3). 28710744 3 27 theme pyruvate 391:398 arg1 F3PYC 418:422 F3PYC 418:422 F3PYC 418:422 In this study, gene walking method was used to clone and characterize pyruvate carboxylase gene (F3PYC) from heavy metal resistant indigenous fungal isolate Aspergillus flavus (F3). 28710744 3 28 theme gene 336:339 arg1 method 349:354 gene walking method 336:354 gene walking method 336:354 In this study, gene walking method was used to clone and characterize pyruvate carboxylase gene (F3PYC) from heavy metal resistant indigenous fungal isolate Aspergillus flavus (F3). 28710744 7 29 from acid 1111:1114 arg1 -N-S-S-I- 1089:1097 -N-S-S-I- 1089:1097 -N-S-S-I- at 36 amino acid 1089:1114 Amongst most possible N-glycosylation sites were -N-S-S-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, N-G-S-S- at 517 amino acid, and N-T-S-R- at 1111 amino acid, with several functions have been proposed for the carbohydrate moiety such as thermal stability, pH, and temperature optima for activity and stabilization of the three-dimensional structure. 28710744 7 29 from acid 1111:1114 arg1 N-T-S-R- 1178:1185 N-T-S-R- 1178:1185 N-T-S-R- at 1111 amino acid 1178:1204 Amongst most possible N-glycosylation sites were -N-S-S-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, N-G-S-S- at 517 amino acid, and N-T-S-R- at 1111 amino acid, with several functions have been proposed for the carbohydrate moiety such as thermal stability, pH, and temperature optima for activity and stabilization of the three-dimensional structure. 28710744 7 29 from acid 1111:1114 arg1 -N-G-T-V- 1117:1125 -N-G-T-V- 1117:1125 -N-G-T-V- at 237 amino acid 1117:1143 Amongst most possible N-glycosylation sites were -N-S-S-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, N-G-S-S- at 517 amino acid, and N-T-S-R- at 1111 amino acid, with several functions have been proposed for the carbohydrate moiety such as thermal stability, pH, and temperature optima for activity and stabilization of the three-dimensional structure. 28710744 7 29 from acid 1111:1114 arg1 N-G-S-S- 1146:1153 N-G-S-S- 1146:1153 N-G-S-S- at 517 amino acid 1146:1171 Amongst most possible N-glycosylation sites were -N-S-S-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, N-G-S-S- at 517 amino acid, and N-T-S-R- at 1111 amino acid, with several functions have been proposed for the carbohydrate moiety such as thermal stability, pH, and temperature optima for activity and stabilization of the three-dimensional structure. 28710744 7 30 theme amino 1162:1166 arg1 acid 1168:1171 517 amino acid 1158:1171 517 amino acid 1158:1171 Amongst most possible N-glycosylation sites were -N-S-S-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, N-G-S-S- at 517 amino acid, and N-T-S-R- at 1111 amino acid, with several functions have been proposed for the carbohydrate moiety such as thermal stability, pH, and temperature optima for activity and stabilization of the three-dimensional structure. 28710744 6 31 dep homotetramer 940:951 arg1 had 1017:1019 had 1017:1019 had no signal peptide 1017:1037 Protein generated from the PYC gene was a homotetramer (α4) and having four potential N-linked glycosylation sites and had no signal peptide. 28710744 6 31 dep homotetramer 940:951 arg1 having 962:967 having 962:967 having four potential N-linked glycosylation sites 962:1011 Protein generated from the PYC gene was a homotetramer (α4) and having four potential N-linked glycosylation sites and had no signal peptide. 28710744 1 32 theme organic 167:173 arg1 acids 175:179 organic acids 167:179 organic acids like; citric acid, fumeric acid, and L-malic acid 167:229 Pyruvate carboxylase is a major enzyme for biosynthesis of organic acids like; citric acid, fumeric acid, and L-malic acid. 28710744 3 33 theme walking 341:347 arg1 method 349:354 gene walking method 336:354 gene walking method 336:354 In this study, gene walking method was used to clone and characterize pyruvate carboxylase gene (F3PYC) from heavy metal resistant indigenous fungal isolate Aspergillus flavus (F3). 28710744 7 34 theme temperature 1312:1322 arg1 optima 1324:1329 temperature optima 1312:1329 temperature optima for activity and stabilization of the three-dimensional structure 1312:1395 Amongst most possible N-glycosylation sites were -N-S-S-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, N-G-S-S- at 517 amino acid, and N-T-S-R- at 1111 amino acid, with several functions have been proposed for the carbohydrate moiety such as thermal stability, pH, and temperature optima for activity and stabilization of the three-dimensional structure. 28710744 4 35 theme 131.2008 kDa 638:649 arg1 weight 628:633 a calculated molecular weight 605:633 a calculated molecular weight of 131.2008 kDa 605:649 3579 bp of an open reading frame which encodes 1193 amino acid protein (isoelectric point: 6.10) with a calculated molecular weight of 131.2008 kDa was characterized. 28710744 7 36 theme structure 1387:1395 arg1 stabilization 1348:1360 stabilization 1348:1360 stabilization 1348:1360 Amongst most possible N-glycosylation sites were -N-S-S-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, N-G-S-S- at 517 amino acid, and N-T-S-R- at 1111 amino acid, with several functions have been proposed for the carbohydrate moiety such as thermal stability, pH, and temperature optima for activity and stabilization of the three-dimensional structure. 28710744 7 36 theme structure 1387:1395 arg1 activity 1335:1342 activity 1335:1342 activity 1335:1342 Amongst most possible N-glycosylation sites were -N-S-S-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, N-G-S-S- at 517 amino acid, and N-T-S-R- at 1111 amino acid, with several functions have been proposed for the carbohydrate moiety such as thermal stability, pH, and temperature optima for activity and stabilization of the three-dimensional structure. 28710744 1 37 theme acids 175:179 arg1 biosynthesis 151:162 biosynthesis 151:162 biosynthesis of organic acids like; citric acid, fumeric acid, and L-malic acid 151:229 Pyruvate carboxylase is a major enzyme for biosynthesis of organic acids like; citric acid, fumeric acid, and L-malic acid. 28710744 7 38 gly N-glycosylation 1062:1076 arg2 sites 1078:1082 most possible N-glycosylation sites 1048:1082 most possible N-glycosylation sites 1048:1082 Amongst most possible N-glycosylation sites were -N-S-S-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, N-G-S-S- at 517 amino acid, and N-T-S-R- at 1111 amino acid, with several functions have been proposed for the carbohydrate moiety such as thermal stability, pH, and temperature optima for activity and stabilization of the three-dimensional structure. 28710744 2 39 theme important 262:270 arg1 role 272:275 very important role 257:275 very important role 257:275 These organic acids play very important role for biological remediation of heavy metals. 28710744 5 40 theme fungal 757:762 arg1 strains 764:770 different fungal strains 747:770 different fungal strains including; Aspergillus parasiticus, Neosartorya fischeri, Aspergillus fumigatus, Aspergillus clavatus, and Aspergillus niger 747:895 Deduced protein showed 90-95% similarity to those deduced from PYC gene from different fungal strains including; Aspergillus parasiticus, Neosartorya fischeri, Aspergillus fumigatus, Aspergillus clavatus, and Aspergillus niger. 28710744 5 41 theme different 747:755 arg1 strains 764:770 different fungal strains 747:770 different fungal strains including; Aspergillus parasiticus, Neosartorya fischeri, Aspergillus fumigatus, Aspergillus clavatus, and Aspergillus niger 747:895 Deduced protein showed 90-95% similarity to those deduced from PYC gene from different fungal strains including; Aspergillus parasiticus, Neosartorya fischeri, Aspergillus fumigatus, Aspergillus clavatus, and Aspergillus niger. 28710744 8 42 theme important 1446:1454 arg1 applications 1473:1484 important biotechnological applications 1446:1484 important biotechnological applications 1446:1484 Hence, cloning of F3PYC gene from A. flavus has important biotechnological applications. 28710744 3 43 theme Aspergillus 478:488 arg1 F3 498:499 F3 498:499 F3 498:499 In this study, gene walking method was used to clone and characterize pyruvate carboxylase gene (F3PYC) from heavy metal resistant indigenous fungal isolate Aspergillus flavus (F3). 28710744 3 43 theme Aspergillus 478:488 arg1 flavus 490:495 heavy metal resistant indigenous fungal isolate Aspergillus flavus 430:495 heavy metal resistant indigenous fungal isolate Aspergillus flavus (F3) 430:500 In this study, gene walking method was used to clone and characterize pyruvate carboxylase gene (F3PYC) from heavy metal resistant indigenous fungal isolate Aspergillus flavus (F3). 28710744 3 44 theme indigenous 452:461 arg1 F3 498:499 F3 498:499 F3 498:499 In this study, gene walking method was used to clone and characterize pyruvate carboxylase gene (F3PYC) from heavy metal resistant indigenous fungal isolate Aspergillus flavus (F3). 28710744 3 44 theme indigenous 452:461 arg1 flavus 490:495 heavy metal resistant indigenous fungal isolate Aspergillus flavus 430:495 heavy metal resistant indigenous fungal isolate Aspergillus flavus (F3) 430:500 In this study, gene walking method was used to clone and characterize pyruvate carboxylase gene (F3PYC) from heavy metal resistant indigenous fungal isolate Aspergillus flavus (F3). 28710744 4 45 theme acid 561:564 arg1 frame 530:534 an open reading frame 514:534 an open reading frame which encodes 1193 amino acid protein (isoelectric point: 6.10) with a calculated molecular weight of 131.2008 kDa 514:649 3579 bp of an open reading frame which encodes 1193 amino acid protein (isoelectric point: 6.10) with a calculated molecular weight of 131.2008 kDa was characterized. 28710744 4 45 theme acid 561:564 arg1 protein 566:572 1193 amino acid protein 550:572 1193 amino acid protein (isoelectric point: 6.10) with a calculated molecular weight of 131.2008 kDa 550:649 3579 bp of an open reading frame which encodes 1193 amino acid protein (isoelectric point: 6.10) with a calculated molecular weight of 131.2008 kDa was characterized. 28710744 0 46 theme gene 38:41 arg1 characterization 12:27 characterization 12:27 characterization 12:27 Cloning and characterization of F3PYC gene encoding pyruvate carboxylase in Aspergillus flavus strain (F3). 28710744 0 46 theme gene 38:41 arg1 Cloning 0:6 Cloning 0:6 Cloning 0:6 Cloning and characterization of F3PYC gene encoding pyruvate carboxylase in Aspergillus flavus strain (F3). 28710744 3 47 theme metal 436:440 arg1 F3 498:499 F3 498:499 F3 498:499 In this study, gene walking method was used to clone and characterize pyruvate carboxylase gene (F3PYC) from heavy metal resistant indigenous fungal isolate Aspergillus flavus (F3). 28710744 3 47 theme metal 436:440 arg1 flavus 490:495 heavy metal resistant indigenous fungal isolate Aspergillus flavus 430:495 heavy metal resistant indigenous fungal isolate Aspergillus flavus (F3) 430:500 In this study, gene walking method was used to clone and characterize pyruvate carboxylase gene (F3PYC) from heavy metal resistant indigenous fungal isolate Aspergillus flavus (F3). 28710744 1 48 theme citric 187:192 arg1 acid 194:197 citric acid 187:197 citric acid 187:197 Pyruvate carboxylase is a major enzyme for biosynthesis of organic acids like; citric acid, fumeric acid, and L-malic acid. 28710744 5 49 theme Neosartorya 808:818 arg1 fischeri 820:827 Neosartorya fischeri 808:827 Neosartorya fischeri 808:827 Deduced protein showed 90-95% similarity to those deduced from PYC gene from different fungal strains including; Aspergillus parasiticus, Neosartorya fischeri, Aspergillus fumigatus, Aspergillus clavatus, and Aspergillus niger. 28710744 3 50 theme carboxylase 400:410 arg1 gene 412:415 pyruvate carboxylase gene 391:415 pyruvate carboxylase gene (F3PYC) from heavy metal resistant indigenous fungal isolate Aspergillus flavus (F3) 391:500 In this study, gene walking method was used to clone and characterize pyruvate carboxylase gene (F3PYC) from heavy metal resistant indigenous fungal isolate Aspergillus flavus (F3). 28710744 3 50 theme carboxylase 400:410 arg1 F3PYC 418:422 F3PYC 418:422 F3PYC 418:422 In this study, gene walking method was used to clone and characterize pyruvate carboxylase gene (F3PYC) from heavy metal resistant indigenous fungal isolate Aspergillus flavus (F3). 28710744 0 51 theme F3PYC 32:36 arg1 gene 38:41 F3PYC gene 32:41 F3PYC gene encoding pyruvate carboxylase in Aspergillus flavus strain (F3) 32:105 Cloning and characterization of F3PYC gene encoding pyruvate carboxylase in Aspergillus flavus strain (F3). 28710744 8 52 theme biotechnological 1456:1471 arg1 applications 1473:1484 important biotechnological applications 1446:1484 important biotechnological applications 1446:1484 Hence, cloning of F3PYC gene from A. flavus has important biotechnological applications. 28710744 7 53 theme amino 1195:1199 arg1 acid 1201:1204 1111 amino acid 1190:1204 1111 amino acid 1190:1204 Amongst most possible N-glycosylation sites were -N-S-S-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, N-G-S-S- at 517 amino acid, and N-T-S-R- at 1111 amino acid, with several functions have been proposed for the carbohydrate moiety such as thermal stability, pH, and temperature optima for activity and stabilization of the three-dimensional structure. 28710744 0 54 theme pyruvate 52:59 arg1 carboxylase 61:71 pyruvate carboxylase 52:71 pyruvate carboxylase in Aspergillus flavus strain (F3) 52:105 Cloning and characterization of F3PYC gene encoding pyruvate carboxylase in Aspergillus flavus strain (F3). 28710744 8 55 theme gene 1422:1425 arg1 cloning 1405:1411 cloning 1405:1411 cloning of F3PYC gene from A. flavus 1405:1440 Hence, cloning of F3PYC gene from A. flavus has important biotechnological applications. 28710744 4 56 theme isoelectric 575:585 arg1 point 587:591 isoelectric point 575:591 isoelectric point: 6.10 575:597 3579 bp of an open reading frame which encodes 1193 amino acid protein (isoelectric point: 6.10) with a calculated molecular weight of 131.2008 kDa was characterized. 28710744 0 57 from carboxylase 61:71 arg1 F3 103:104 F3 103:104 F3 103:104 Cloning and characterization of F3PYC gene encoding pyruvate carboxylase in Aspergillus flavus strain (F3). 28710744 0 57 from carboxylase 61:71 arg1 strain 95:100 Aspergillus flavus strain 76:100 Aspergillus flavus strain (F3) 76:105 Cloning and characterization of F3PYC gene encoding pyruvate carboxylase in Aspergillus flavus strain (F3). 28710744 4 58 dep protein 566:572 arg1 point 587:591 isoelectric point 575:591 isoelectric point: 6.10 575:597 3579 bp of an open reading frame which encodes 1193 amino acid protein (isoelectric point: 6.10) with a calculated molecular weight of 131.2008 kDa was characterized. 28710744 2 59 theme heavy 307:311 arg1 metals 313:318 heavy metals 307:318 heavy metals 307:318 These organic acids play very important role for biological remediation of heavy metals. 28710744 7 60 theme several 1212:1218 arg1 functions 1220:1228 several functions 1212:1228 several functions 1212:1228 Amongst most possible N-glycosylation sites were -N-S-S-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, N-G-S-S- at 517 amino acid, and N-T-S-R- at 1111 amino acid, with several functions have been proposed for the carbohydrate moiety such as thermal stability, pH, and temperature optima for activity and stabilization of the three-dimensional structure. 28710744 1 61 theme major 134:138 arg1 carboxylase 117:127 Pyruvate carboxylase 108:127 Pyruvate carboxylase 108:127 Pyruvate carboxylase is a major enzyme for biosynthesis of organic acids like; citric acid, fumeric acid, and L-malic acid. 28710744 1 61 theme major 134:138 arg1 enzyme 140:145 a major enzyme 132:145 a major enzyme for biosynthesis of organic acids like; citric acid, fumeric acid, and L-malic acid 132:229 Pyruvate carboxylase is a major enzyme for biosynthesis of organic acids like; citric acid, fumeric acid, and L-malic acid. 28710744 7 62 from acid 1201:1204 arg1 -N-S-S-I- 1089:1097 -N-S-S-I- 1089:1097 -N-S-S-I- at 36 amino acid 1089:1114 Amongst most possible N-glycosylation sites were -N-S-S-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, N-G-S-S- at 517 amino acid, and N-T-S-R- at 1111 amino acid, with several functions have been proposed for the carbohydrate moiety such as thermal stability, pH, and temperature optima for activity and stabilization of the three-dimensional structure. 28710744 7 62 from acid 1201:1204 arg1 N-T-S-R- 1178:1185 N-T-S-R- 1178:1185 N-T-S-R- at 1111 amino acid 1178:1204 Amongst most possible N-glycosylation sites were -N-S-S-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, N-G-S-S- at 517 amino acid, and N-T-S-R- at 1111 amino acid, with several functions have been proposed for the carbohydrate moiety such as thermal stability, pH, and temperature optima for activity and stabilization of the three-dimensional structure. 28710744 7 62 from acid 1201:1204 arg1 -N-G-T-V- 1117:1125 -N-G-T-V- 1117:1125 -N-G-T-V- at 237 amino acid 1117:1143 Amongst most possible N-glycosylation sites were -N-S-S-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, N-G-S-S- at 517 amino acid, and N-T-S-R- at 1111 amino acid, with several functions have been proposed for the carbohydrate moiety such as thermal stability, pH, and temperature optima for activity and stabilization of the three-dimensional structure. 28710744 7 62 from acid 1201:1204 arg1 N-G-S-S- 1146:1153 N-G-S-S- 1146:1153 N-G-S-S- at 517 amino acid 1146:1171 Amongst most possible N-glycosylation sites were -N-S-S-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, N-G-S-S- at 517 amino acid, and N-T-S-R- at 1111 amino acid, with several functions have been proposed for the carbohydrate moiety such as thermal stability, pH, and temperature optima for activity and stabilization of the three-dimensional structure. 28710744 1 63 theme Pyruvate 108:115 arg1 carboxylase 117:127 Pyruvate carboxylase 108:127 Pyruvate carboxylase 108:127 Pyruvate carboxylase is a major enzyme for biosynthesis of organic acids like; citric acid, fumeric acid, and L-malic acid. 28710744 1 63 theme Pyruvate 108:115 arg1 enzyme 140:145 a major enzyme 132:145 a major enzyme for biosynthesis of organic acids like; citric acid, fumeric acid, and L-malic acid 132:229 Pyruvate carboxylase is a major enzyme for biosynthesis of organic acids like; citric acid, fumeric acid, and L-malic acid. 28710744 5 64 dep strains 764:770 arg1 niger 891:895 Aspergillus niger 879:895 Aspergillus niger 879:895 Deduced protein showed 90-95% similarity to those deduced from PYC gene from different fungal strains including; Aspergillus parasiticus, Neosartorya fischeri, Aspergillus fumigatus, Aspergillus clavatus, and Aspergillus niger. 28710744 5 64 dep strains 764:770 arg1 parasiticus 795:805 Aspergillus parasiticus 783:805 Aspergillus parasiticus 783:805 Deduced protein showed 90-95% similarity to those deduced from PYC gene from different fungal strains including; Aspergillus parasiticus, Neosartorya fischeri, Aspergillus fumigatus, Aspergillus clavatus, and Aspergillus niger. 28710744 5 64 dep strains 764:770 arg1 fischeri 820:827 Neosartorya fischeri 808:827 Neosartorya fischeri 808:827 Deduced protein showed 90-95% similarity to those deduced from PYC gene from different fungal strains including; Aspergillus parasiticus, Neosartorya fischeri, Aspergillus fumigatus, Aspergillus clavatus, and Aspergillus niger. 28710744 5 64 dep strains 764:770 arg1 fumigatus 842:850 Aspergillus fumigatus 830:850 Aspergillus fumigatus 830:850 Deduced protein showed 90-95% similarity to those deduced from PYC gene from different fungal strains including; Aspergillus parasiticus, Neosartorya fischeri, Aspergillus fumigatus, Aspergillus clavatus, and Aspergillus niger. 28710744 5 64 dep strains 764:770 arg1 clavatus 865:872 Aspergillus clavatus 853:872 Aspergillus clavatus 853:872 Deduced protein showed 90-95% similarity to those deduced from PYC gene from different fungal strains including; Aspergillus parasiticus, Neosartorya fischeri, Aspergillus fumigatus, Aspergillus clavatus, and Aspergillus niger. 28710744 7 65 theme amino 1105:1109 arg1 acid 1111:1114 36 amino acid 1102:1114 36 amino acid 1102:1114 Amongst most possible N-glycosylation sites were -N-S-S-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, N-G-S-S- at 517 amino acid, and N-T-S-R- at 1111 amino acid, with several functions have been proposed for the carbohydrate moiety such as thermal stability, pH, and temperature optima for activity and stabilization of the three-dimensional structure. 28710744 7 66 theme thermal 1285:1291 arg1 stability 1293:1301 thermal stability 1285:1301 thermal stability 1285:1301 Amongst most possible N-glycosylation sites were -N-S-S-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, N-G-S-S- at 517 amino acid, and N-T-S-R- at 1111 amino acid, with several functions have been proposed for the carbohydrate moiety such as thermal stability, pH, and temperature optima for activity and stabilization of the three-dimensional structure. 28710744 5 67 theme Deduced 670:676 arg1 protein 678:684 Deduced protein 670:684 Deduced protein 670:684 Deduced protein showed 90-95% similarity to those deduced from PYC gene from different fungal strains including; Aspergillus parasiticus, Neosartorya fischeri, Aspergillus fumigatus, Aspergillus clavatus, and Aspergillus niger. 28710744 3 68 used used 360:363 arg2 method 349:354 gene walking method 336:354 gene walking method 336:354 In this study, gene walking method was used to clone and characterize pyruvate carboxylase gene (F3PYC) from heavy metal resistant indigenous fungal isolate Aspergillus flavus (F3). 28710744 4 69 with protein 566:572 arg1 weight 628:633 a calculated molecular weight 605:633 a calculated molecular weight of 131.2008 kDa 605:649 3579 bp of an open reading frame which encodes 1193 amino acid protein (isoelectric point: 6.10) with a calculated molecular weight of 131.2008 kDa was characterized. 28710744 6 70 theme N-linked 984:991 arg1 sites 1007:1011 four potential N-linked glycosylation sites 969:1011 four potential N-linked glycosylation sites 969:1011 Protein generated from the PYC gene was a homotetramer (α4) and having four potential N-linked glycosylation sites and had no signal peptide. 28710744 7 71 theme amino 1134:1138 arg1 acid 1140:1143 237 amino acid 1130:1143 237 amino acid 1130:1143 Amongst most possible N-glycosylation sites were -N-S-S-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, N-G-S-S- at 517 amino acid, and N-T-S-R- at 1111 amino acid, with several functions have been proposed for the carbohydrate moiety such as thermal stability, pH, and temperature optima for activity and stabilization of the three-dimensional structure. 28710744 2 72 theme biological 281:290 arg1 remediation 292:302 biological remediation 281:302 biological remediation of heavy metals 281:318 These organic acids play very important role for biological remediation of heavy metals. 28710744 1 73 theme fumeric 200:206 arg1 acid 208:211 fumeric acid 200:211 fumeric acid 200:211 Pyruvate carboxylase is a major enzyme for biosynthesis of organic acids like; citric acid, fumeric acid, and L-malic acid. 28710744 6 74 theme signal 1024:1029 arg1 peptide 1031:1037 no signal peptide 1021:1037 no signal peptide 1021:1037 Protein generated from the PYC gene was a homotetramer (α4) and having four potential N-linked glycosylation sites and had no signal peptide. 28710744 6 75 theme potential 974:982 arg1 sites 1007:1011 four potential N-linked glycosylation sites 969:1011 four potential N-linked glycosylation sites 969:1011 Protein generated from the PYC gene was a homotetramer (α4) and having four potential N-linked glycosylation sites and had no signal peptide. 28710744 3 76 theme fungal 463:468 arg1 F3 498:499 F3 498:499 F3 498:499 In this study, gene walking method was used to clone and characterize pyruvate carboxylase gene (F3PYC) from heavy metal resistant indigenous fungal isolate Aspergillus flavus (F3). 28710744 3 76 theme fungal 463:468 arg1 flavus 490:495 heavy metal resistant indigenous fungal isolate Aspergillus flavus 430:495 heavy metal resistant indigenous fungal isolate Aspergillus flavus (F3) 430:500 In this study, gene walking method was used to clone and characterize pyruvate carboxylase gene (F3PYC) from heavy metal resistant indigenous fungal isolate Aspergillus flavus (F3). 28710744 7 77 from acid 1140:1143 arg1 -N-S-S-I- 1089:1097 -N-S-S-I- 1089:1097 -N-S-S-I- at 36 amino acid 1089:1114 Amongst most possible N-glycosylation sites were -N-S-S-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, N-G-S-S- at 517 amino acid, and N-T-S-R- at 1111 amino acid, with several functions have been proposed for the carbohydrate moiety such as thermal stability, pH, and temperature optima for activity and stabilization of the three-dimensional structure. 28710744 7 77 from acid 1140:1143 arg1 N-T-S-R- 1178:1185 N-T-S-R- 1178:1185 N-T-S-R- at 1111 amino acid 1178:1204 Amongst most possible N-glycosylation sites were -N-S-S-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, N-G-S-S- at 517 amino acid, and N-T-S-R- at 1111 amino acid, with several functions have been proposed for the carbohydrate moiety such as thermal stability, pH, and temperature optima for activity and stabilization of the three-dimensional structure. 28710744 7 77 from acid 1140:1143 arg1 -N-G-T-V- 1117:1125 -N-G-T-V- 1117:1125 -N-G-T-V- at 237 amino acid 1117:1143 Amongst most possible N-glycosylation sites were -N-S-S-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, N-G-S-S- at 517 amino acid, and N-T-S-R- at 1111 amino acid, with several functions have been proposed for the carbohydrate moiety such as thermal stability, pH, and temperature optima for activity and stabilization of the three-dimensional structure. 28710744 7 77 from acid 1140:1143 arg1 N-G-S-S- 1146:1153 N-G-S-S- 1146:1153 N-G-S-S- at 517 amino acid 1146:1171 Amongst most possible N-glycosylation sites were -N-S-S-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, N-G-S-S- at 517 amino acid, and N-T-S-R- at 1111 amino acid, with several functions have been proposed for the carbohydrate moiety such as thermal stability, pH, and temperature optima for activity and stabilization of the three-dimensional structure. 28710744 4 78 theme amino 555:559 arg1 frame 530:534 an open reading frame 514:534 an open reading frame which encodes 1193 amino acid protein (isoelectric point: 6.10) with a calculated molecular weight of 131.2008 kDa 514:649 3579 bp of an open reading frame which encodes 1193 amino acid protein (isoelectric point: 6.10) with a calculated molecular weight of 131.2008 kDa was characterized. 28710744 4 78 theme amino 555:559 arg1 protein 566:572 1193 amino acid protein 550:572 1193 amino acid protein (isoelectric point: 6.10) with a calculated molecular weight of 131.2008 kDa 550:649 3579 bp of an open reading frame which encodes 1193 amino acid protein (isoelectric point: 6.10) with a calculated molecular weight of 131.2008 kDa was characterized. 28710744 5 79 theme 90-95 693:697 arg1 % 698:698 % 698:698 % 698:698 Deduced protein showed 90-95% similarity to those deduced from PYC gene from different fungal strains including; Aspergillus parasiticus, Neosartorya fischeri, Aspergillus fumigatus, Aspergillus clavatus, and Aspergillus niger. 28710744 7 80 theme three-dimensional 1369:1385 arg1 structure 1387:1395 the three-dimensional structure 1365:1395 the three-dimensional structure 1365:1395 Amongst most possible N-glycosylation sites were -N-S-S-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, N-G-S-S- at 517 amino acid, and N-T-S-R- at 1111 amino acid, with several functions have been proposed for the carbohydrate moiety such as thermal stability, pH, and temperature optima for activity and stabilization of the three-dimensional structure. 28710744 4 81 dep point 587:591 arg1 6.10 594:597 6.10 594:597 6.10 594:597 3579 bp of an open reading frame which encodes 1193 amino acid protein (isoelectric point: 6.10) with a calculated molecular weight of 131.2008 kDa was characterized. 28710744 3 82 theme isolate 470:476 arg1 F3 498:499 F3 498:499 F3 498:499 In this study, gene walking method was used to clone and characterize pyruvate carboxylase gene (F3PYC) from heavy metal resistant indigenous fungal isolate Aspergillus flavus (F3). 28710744 3 82 theme isolate 470:476 arg1 flavus 490:495 heavy metal resistant indigenous fungal isolate Aspergillus flavus 430:495 heavy metal resistant indigenous fungal isolate Aspergillus flavus (F3) 430:500 In this study, gene walking method was used to clone and characterize pyruvate carboxylase gene (F3PYC) from heavy metal resistant indigenous fungal isolate Aspergillus flavus (F3). 28710744 4 83 theme 1193 550:553 arg1 frame 530:534 an open reading frame 514:534 an open reading frame which encodes 1193 amino acid protein (isoelectric point: 6.10) with a calculated molecular weight of 131.2008 kDa 514:649 3579 bp of an open reading frame which encodes 1193 amino acid protein (isoelectric point: 6.10) with a calculated molecular weight of 131.2008 kDa was characterized. 28710744 4 83 theme 1193 550:553 arg1 protein 566:572 1193 amino acid protein 550:572 1193 amino acid protein (isoelectric point: 6.10) with a calculated molecular weight of 131.2008 kDa 550:649 3579 bp of an open reading frame which encodes 1193 amino acid protein (isoelectric point: 6.10) with a calculated molecular weight of 131.2008 kDa was characterized. 28452380 6 0 theme estimated 841:849 arg1 weight 861:866 an estimated molecular weight 838:866 an estimated molecular weight of 140-160 kDa and a pI predominantly 5.8 838:908 RESULTS Molecular forms of DPP-IV with an estimated molecular weight of 140-160 kDa and a pI predominantly 5.8 were detected in human glioblastoma; in some tumors additional isoforms with a more acidic (3.5-5.5) as well as alkaline (8.1) pI were revealed. 28452380 11 1 theme glioblastoma 1816:1827 arg1 tissues 1829:1835 glioblastoma tissues 1816:1835 glioblastoma tissues 1816:1835 The absence of alkaline isoforms of both enzymes in glioma cell lines however suggests that isoforms from other, most likely stromal, cell types contribute to the overall pattern seen in glioblastoma tissues. 28452380 4 2 dep METHODS 486:492 arg1 focusing 513:520 focusing 513:520 focusing 513:520 METHODS ELISA, isoelectric focusing, 1D and 2D electrophoresis followed by WB or enzyme overlay assay were utilized to analyze DPP-IV and FAP isoforms. 28452380 4 2 dep METHODS 486:492 arg1 electrophoresis 533:547 2D electrophoresis 530:547 2D electrophoresis 530:547 METHODS ELISA, isoelectric focusing, 1D and 2D electrophoresis followed by WB or enzyme overlay assay were utilized to analyze DPP-IV and FAP isoforms. 28452380 4 2 dep METHODS 486:492 arg1 METHODS 486:492 METHODS ELISA, isoelectric focusing, 1D and 2D electrophoresis 486:547 METHODS ELISA, isoelectric focusing, 1D and 2D electrophoresis followed by WB or enzyme overlay assay 486:586 METHODS ELISA, isoelectric focusing, 1D and 2D electrophoresis followed by WB or enzyme overlay assay were utilized to analyze DPP-IV and FAP isoforms. 28452380 4 2 dep METHODS 486:492 arg1 1D 523:524 1D 523:524 1D 523:524 METHODS ELISA, isoelectric focusing, 1D and 2D electrophoresis followed by WB or enzyme overlay assay were utilized to analyze DPP-IV and FAP isoforms. 28452380 4 2 dep METHODS 486:492 arg1 ELISA 494:498 ELISA 494:498 ELISA 494:498 METHODS ELISA, isoelectric focusing, 1D and 2D electrophoresis followed by WB or enzyme overlay assay were utilized to analyze DPP-IV and FAP isoforms. 28452380 4 3 theme DPP-IV 613:618 arg1 isoforms 628:635 DPP-IV and FAP isoforms 613:635 isoforms 628:635 METHODS ELISA, isoelectric focusing, 1D and 2D electrophoresis followed by WB or enzyme overlay assay were utilized to analyze DPP-IV and FAP isoforms. 28452380 6 4 dep RESULTS 799:805 arg1 forms 817:821 Molecular forms 807:821 RESULTS Molecular forms of DPP-IV with an estimated molecular weight of 140-160 kDa and a pI predominantly 5.8 799:908 RESULTS Molecular forms of DPP-IV with an estimated molecular weight of 140-160 kDa and a pI predominantly 5.8 were detected in human glioblastoma; in some tumors additional isoforms with a more acidic (3.5-5.5) as well as alkaline (8.1) pI were revealed. 28452380 2 5 dep peptidases 276:285 arg1 peptidases 276:285 the proline specific peptidases 255:285 the proline specific peptidases dipeptidyl peptidase-IV (DPP-IV) and its closest paralogue fibroblast activation protein (FAP) 255:380 We previously reported increased expression of the proline specific peptidases dipeptidyl peptidase-IV (DPP-IV) and its closest paralogue fibroblast activation protein (FAP) in human glioblastomas. 28452380 2 5 dep peptidases 276:285 arg1 paralogue 336:344 its closest paralogue fibroblast activation protein (FAP) 324:380 its closest paralogue fibroblast activation protein (FAP) 324:380 We previously reported increased expression of the proline specific peptidases dipeptidyl peptidase-IV (DPP-IV) and its closest paralogue fibroblast activation protein (FAP) in human glioblastomas. 28452380 2 5 dep peptidases 276:285 arg1 DPP-IV 312:317 DPP-IV 312:317 DPP-IV 312:317 We previously reported increased expression of the proline specific peptidases dipeptidyl peptidase-IV (DPP-IV) and its closest paralogue fibroblast activation protein (FAP) in human glioblastomas. 28452380 2 5 dep peptidases 276:285 arg1 peptidase-IV 298:309 dipeptidyl peptidase-IV 287:309 dipeptidyl peptidase-IV (DPP-IV) 287:318 We previously reported increased expression of the proline specific peptidases dipeptidyl peptidase-IV (DPP-IV) and its closest paralogue fibroblast activation protein (FAP) in human glioblastomas. 28452380 8 6 from present 1329:1335 arg1 tissues 1353:1359 glioblastoma tissues 1340:1359 glioblastoma tissues 1340:1359 In glioma cell lines in vitro, several isoforms of both enzymes were expressed, however the alkalic forms present in glioblastoma tissues were not detected. 28452380 1 7 theme various 191:197 arg1 cancers 199:205 various cancers 191:205 various cancers 191:205 BACKGROUND AND AIMS Proteolytic enzymes contribute to the progression of various cancers. 28452380 7 8 dep three 1088:1092 arg1 to 1085:1086 to 1085:1086 to 1085:1086 Using 2D electrophoresis, two to three molecular forms of FAP with an alkaline (7.0-8.5) pI and an estimated MW of 120-140 kDa were identified in glioblastoma tissues. 28452380 6 9 theme Molecular 807:815 arg1 forms 817:821 Molecular forms 807:821 RESULTS Molecular forms of DPP-IV with an estimated molecular weight of 140-160 kDa and a pI predominantly 5.8 799:908 RESULTS Molecular forms of DPP-IV with an estimated molecular weight of 140-160 kDa and a pI predominantly 5.8 were detected in human glioblastoma; in some tumors additional isoforms with a more acidic (3.5-5.5) as well as alkaline (8.1) pI were revealed. 28452380 9 10 theme N-linked 1391:1398 arg1 oligosaccharides 1400:1415 N-linked oligosaccharides 1391:1415 N-linked oligosaccharides 1391:1415 Removal of N-linked oligosaccharides decreased the estimated molecular weight of both enzymes; the overall pattern of molecular forms nevertheless remained unchanged. 28452380 10 11 theme CONCLUSION 1547:1556 arg1 isoforms 1566:1573 CONCLUSION Several isoforms 1547:1573 CONCLUSION Several isoforms of DPP-IV and FAP 1547:1591 CONCLUSION Several isoforms of DPP-IV and FAP are present in glioblastoma tissue. 28452380 8 12 theme glioma 1226:1231 arg1 lines 1238:1242 glioma cell lines 1226:1242 glioma cell lines in vitro 1226:1251 In glioma cell lines in vitro, several isoforms of both enzymes were expressed, however the alkalic forms present in glioblastoma tissues were not detected. 28452380 10 13 theme FAP 1589:1591 arg1 isoforms 1566:1573 CONCLUSION Several isoforms 1547:1573 CONCLUSION Several isoforms of DPP-IV and FAP 1547:1591 CONCLUSION Several isoforms of DPP-IV and FAP are present in glioblastoma tissue. 28452380 7 14 theme alkaline 1125:1132 arg1 pI 1144:1145 an alkaline (7.0-8.5) pI 1122:1145 an alkaline (7.0-8.5) pI 1122:1145 Using 2D electrophoresis, two to three molecular forms of FAP with an alkaline (7.0-8.5) pI and an estimated MW of 120-140 kDa were identified in glioblastoma tissues. 28452380 9 15 theme estimated 1431:1439 arg1 weight 1451:1456 the estimated molecular weight 1427:1456 the estimated molecular weight of both enzymes 1427:1472 Removal of N-linked oligosaccharides decreased the estimated molecular weight of both enzymes; the overall pattern of molecular forms nevertheless remained unchanged. 28452380 10 16 theme DPP-IV 1578:1583 arg1 isoforms 1566:1573 CONCLUSION Several isoforms 1547:1573 CONCLUSION Several isoforms of DPP-IV and FAP 1547:1591 CONCLUSION Several isoforms of DPP-IV and FAP are present in glioblastoma tissue. 28452380 11 17 theme cell 1763:1766 arg1 types 1768:1772 other, most likely stromal, cell types 1735:1772 other, most likely stromal, cell types 1735:1772 The absence of alkaline isoforms of both enzymes in glioma cell lines however suggests that isoforms from other, most likely stromal, cell types contribute to the overall pattern seen in glioblastoma tissues. 28452380 5 18 theme PNGase 707:712 arg1 F 714:714 PNGase F 707:714 PNGase F 707:714 Cell fractionation using a Percoll gradient and deglycosylation with PNGase F were performed to analyze the possible basis of DPP-IV and FAP microheterogeneity. 28452380 1 19 theme AIMS 133:136 arg1 enzymes 150:156 BACKGROUND AND AIMS Proteolytic enzymes 118:156 BACKGROUND AND AIMS Proteolytic enzymes 118:156 BACKGROUND AND AIMS Proteolytic enzymes contribute to the progression of various cancers. 28452380 11 20 dep other 1735:1739 arg1 stromal 1754:1760 stromal 1754:1760 stromal 1754:1760 The absence of alkaline isoforms of both enzymes in glioma cell lines however suggests that isoforms from other, most likely stromal, cell types contribute to the overall pattern seen in glioblastoma tissues. 28452380 2 21 theme dipeptidyl 287:296 arg1 peptidases 276:285 the proline specific peptidases 255:285 the proline specific peptidases dipeptidyl peptidase-IV (DPP-IV) and its closest paralogue fibroblast activation protein (FAP) 255:380 We previously reported increased expression of the proline specific peptidases dipeptidyl peptidase-IV (DPP-IV) and its closest paralogue fibroblast activation protein (FAP) in human glioblastomas. 28452380 2 21 theme dipeptidyl 287:296 arg1 DPP-IV 312:317 DPP-IV 312:317 DPP-IV 312:317 We previously reported increased expression of the proline specific peptidases dipeptidyl peptidase-IV (DPP-IV) and its closest paralogue fibroblast activation protein (FAP) in human glioblastomas. 28452380 2 21 theme dipeptidyl 287:296 arg1 peptidase-IV 298:309 dipeptidyl peptidase-IV 287:309 dipeptidyl peptidase-IV (DPP-IV) 287:318 We previously reported increased expression of the proline specific peptidases dipeptidyl peptidase-IV (DPP-IV) and its closest paralogue fibroblast activation protein (FAP) in human glioblastomas. 28452380 8 22 theme several 1254:1260 arg1 isoforms 1262:1269 several isoforms 1254:1269 several isoforms of both enzymes 1254:1285 In glioma cell lines in vitro, several isoforms of both enzymes were expressed, however the alkalic forms present in glioblastoma tissues were not detected. 28452380 7 23 theme kDa 1178:1180 arg1 MW 1164:1165 an estimated MW 1151:1165 an estimated MW of 120-140 kDa 1151:1180 Using 2D electrophoresis, two to three molecular forms of FAP with an alkaline (7.0-8.5) pI and an estimated MW of 120-140 kDa were identified in glioblastoma tissues. 28452380 7 23 theme kDa 1178:1180 arg1 forms 1104:1108 two to three molecular forms 1081:1108 two to three molecular forms of FAP with an alkaline (7.0-8.5) pI 1081:1145 Using 2D electrophoresis, two to three molecular forms of FAP with an alkaline (7.0-8.5) pI and an estimated MW of 120-140 kDa were identified in glioblastoma tissues. 28452380 2 24 theme specific 267:274 arg1 peptidases 276:285 the proline specific peptidases 255:285 the proline specific peptidases dipeptidyl peptidase-IV (DPP-IV) and its closest paralogue fibroblast activation protein (FAP) 255:380 We previously reported increased expression of the proline specific peptidases dipeptidyl peptidase-IV (DPP-IV) and its closest paralogue fibroblast activation protein (FAP) in human glioblastomas. 28452380 2 24 theme specific 267:274 arg1 paralogue 336:344 its closest paralogue fibroblast activation protein (FAP) 324:380 its closest paralogue fibroblast activation protein (FAP) 324:380 We previously reported increased expression of the proline specific peptidases dipeptidyl peptidase-IV (DPP-IV) and its closest paralogue fibroblast activation protein (FAP) in human glioblastomas. 28452380 2 24 theme specific 267:274 arg1 peptidase-IV 298:309 dipeptidyl peptidase-IV 287:309 dipeptidyl peptidase-IV (DPP-IV) 287:318 We previously reported increased expression of the proline specific peptidases dipeptidyl peptidase-IV (DPP-IV) and its closest paralogue fibroblast activation protein (FAP) in human glioblastomas. 28452380 11 25 theme other 1735:1739 arg1 types 1768:1772 other, most likely stromal, cell types 1735:1772 other, most likely stromal, cell types 1735:1772 The absence of alkaline isoforms of both enzymes in glioma cell lines however suggests that isoforms from other, most likely stromal, cell types contribute to the overall pattern seen in glioblastoma tissues. 28452380 0 26 theme protein 86:92 arg1 forms 27:31 molecular forms 17:31 molecular forms of dipeptidyl peptidase-IV and fibroblast activation protein 17:92 Heterogeneity of molecular forms of dipeptidyl peptidase-IV and fibroblast activation protein in human glioblastomas. 28452380 3 27 from heterogeneity 436:448 arg1 glioblastomas 471:483 glioblastomas 471:483 glioblastomas 471:483 Here we analyze the molecular heterogeneity of DPP-IV and FAP in glioblastomas. 28452380 3 28 gly heterogeneity 436:448 arg1 FAP 464:466 FAP 464:466 FAP 464:466 Here we analyze the molecular heterogeneity of DPP-IV and FAP in glioblastomas. 28452380 3 28 gly heterogeneity 436:448 arg1 DPP-IV 453:458 DPP-IV 453:458 DPP-IV 453:458 Here we analyze the molecular heterogeneity of DPP-IV and FAP in glioblastomas. 28452380 9 29 theme overall 1479:1485 arg1 pattern 1487:1493 the overall pattern 1475:1493 the overall pattern of molecular forms 1475:1512 Removal of N-linked oligosaccharides decreased the estimated molecular weight of both enzymes; the overall pattern of molecular forms nevertheless remained unchanged. 28452380 0 30 from Heterogeneity 0:12 arg1 glioblastomas 103:115 human glioblastomas 97:115 human glioblastomas 97:115 Heterogeneity of molecular forms of dipeptidyl peptidase-IV and fibroblast activation protein in human glioblastomas. 28452380 8 31 theme enzymes 1279:1285 arg1 isoforms 1262:1269 several isoforms 1254:1269 several isoforms of both enzymes 1254:1285 In glioma cell lines in vitro, several isoforms of both enzymes were expressed, however the alkalic forms present in glioblastoma tissues were not detected. 28452380 0 32 theme human 97:101 arg1 glioblastomas 103:115 human glioblastomas 97:115 human glioblastomas 97:115 Heterogeneity of molecular forms of dipeptidyl peptidase-IV and fibroblast activation protein in human glioblastomas. 28452380 6 33 with isoforms 973:980 arg1 3.5-5.5 1002:1008 3.5-5.5 1002:1008 3.5-5.5 1002:1008 RESULTS Molecular forms of DPP-IV with an estimated molecular weight of 140-160 kDa and a pI predominantly 5.8 were detected in human glioblastoma; in some tumors additional isoforms with a more acidic (3.5-5.5) as well as alkaline (8.1) pI were revealed. 28452380 6 33 with isoforms 973:980 arg1 acidic 994:999 acidic 994:999 acidic 994:999 RESULTS Molecular forms of DPP-IV with an estimated molecular weight of 140-160 kDa and a pI predominantly 5.8 were detected in human glioblastoma; in some tumors additional isoforms with a more acidic (3.5-5.5) as well as alkaline (8.1) pI were revealed. 28452380 6 33 with isoforms 973:980 arg1 pI 1037:1038 alkaline (8.1) pI 1022:1038 a more acidic (3.5-5.5) as well as alkaline (8.1) pI 987:1038 RESULTS Molecular forms of DPP-IV with an estimated molecular weight of 140-160 kDa and a pI predominantly 5.8 were detected in human glioblastoma; in some tumors additional isoforms with a more acidic (3.5-5.5) as well as alkaline (8.1) pI were revealed. 28452380 3 34 theme FAP 464:466 arg1 heterogeneity 436:448 the molecular heterogeneity 422:448 the molecular heterogeneity of DPP-IV and FAP in glioblastomas 422:483 Here we analyze the molecular heterogeneity of DPP-IV and FAP in glioblastomas. 28452380 5 35 theme DPP-IV 764:769 arg1 basis 755:759 the possible basis 742:759 the possible basis of DPP-IV and FAP microheterogeneity 742:796 Cell fractionation using a Percoll gradient and deglycosylation with PNGase F were performed to analyze the possible basis of DPP-IV and FAP microheterogeneity. 28452380 9 36 link N-linked 1391:1398 arg1 oligosaccharides 1400:1415 N-linked oligosaccharides 1391:1415 N-linked oligosaccharides 1391:1415 Removal of N-linked oligosaccharides decreased the estimated molecular weight of both enzymes; the overall pattern of molecular forms nevertheless remained unchanged. 28452380 9 37 theme forms 1508:1512 arg1 pattern 1487:1493 the overall pattern 1475:1493 the overall pattern of molecular forms 1475:1512 Removal of N-linked oligosaccharides decreased the estimated molecular weight of both enzymes; the overall pattern of molecular forms nevertheless remained unchanged. 28452380 10 38 attach present 1597:1603 arg1 tissue 1621:1626 glioblastoma tissue 1608:1626 glioblastoma tissue 1608:1626 CONCLUSION Several isoforms of DPP-IV and FAP are present in glioblastoma tissue. 28452380 10 38 attach present 1597:1603 arg2 isoforms 1566:1573 CONCLUSION Several isoforms 1547:1573 CONCLUSION Several isoforms of DPP-IV and FAP 1547:1591 CONCLUSION Several isoforms of DPP-IV and FAP are present in glioblastoma tissue. 28452380 3 39 theme DPP-IV 453:458 arg1 heterogeneity 436:448 the molecular heterogeneity 422:448 the molecular heterogeneity of DPP-IV and FAP in glioblastomas 422:483 Here we analyze the molecular heterogeneity of DPP-IV and FAP in glioblastomas. 28452380 8 40 attach present 1329:1335 arg2 forms 1323:1327 the alkalic forms 1311:1327 the alkalic forms present in glioblastoma tissues 1311:1359 In glioma cell lines in vitro, several isoforms of both enzymes were expressed, however the alkalic forms present in glioblastoma tissues were not detected. 28452380 8 40 attach present 1329:1335 arg1 tissues 1353:1359 glioblastoma tissues 1340:1359 glioblastoma tissues 1340:1359 In glioma cell lines in vitro, several isoforms of both enzymes were expressed, however the alkalic forms present in glioblastoma tissues were not detected. 28452380 11 41 from absence 1633:1639 arg1 lines 1693:1697 glioma cell lines 1681:1697 glioma cell lines 1681:1697 The absence of alkaline isoforms of both enzymes in glioma cell lines however suggests that isoforms from other, most likely stromal, cell types contribute to the overall pattern seen in glioblastoma tissues. 28452380 4 42 theme enzyme 567:572 arg1 assay 582:586 WB or enzyme overlay assay 561:586 assay 582:586 METHODS ELISA, isoelectric focusing, 1D and 2D electrophoresis followed by WB or enzyme overlay assay were utilized to analyze DPP-IV and FAP isoforms. 28452380 8 43 theme alkalic 1315:1321 arg1 forms 1323:1327 the alkalic forms 1311:1327 the alkalic forms present in glioblastoma tissues 1311:1359 In glioma cell lines in vitro, several isoforms of both enzymes were expressed, however the alkalic forms present in glioblastoma tissues were not detected. 28452380 0 44 theme molecular 17:25 arg1 forms 27:31 molecular forms 17:31 molecular forms of dipeptidyl peptidase-IV and fibroblast activation protein 17:92 Heterogeneity of molecular forms of dipeptidyl peptidase-IV and fibroblast activation protein in human glioblastomas. 28452380 6 45 theme pI 889:890 arg1 weight 861:866 an estimated molecular weight 838:866 an estimated molecular weight of 140-160 kDa and a pI predominantly 5.8 838:908 RESULTS Molecular forms of DPP-IV with an estimated molecular weight of 140-160 kDa and a pI predominantly 5.8 were detected in human glioblastoma; in some tumors additional isoforms with a more acidic (3.5-5.5) as well as alkaline (8.1) pI were revealed. 28452380 1 46 theme BACKGROUND 118:127 arg1 enzymes 150:156 BACKGROUND AND AIMS Proteolytic enzymes 118:156 BACKGROUND AND AIMS Proteolytic enzymes 118:156 BACKGROUND AND AIMS Proteolytic enzymes contribute to the progression of various cancers. 28452380 0 47 theme fibroblast 64:73 arg1 protein 86:92 fibroblast activation protein 64:92 fibroblast activation protein 64:92 Heterogeneity of molecular forms of dipeptidyl peptidase-IV and fibroblast activation protein in human glioblastomas. 28452380 8 48 theme present 1329:1335 arg1 forms 1323:1327 the alkalic forms 1311:1327 the alkalic forms present in glioblastoma tissues 1311:1359 In glioma cell lines in vitro, several isoforms of both enzymes were expressed, however the alkalic forms present in glioblastoma tissues were not detected. 28452380 5 49 theme FAP 775:777 arg1 microheterogeneity 779:796 FAP microheterogeneity 775:796 FAP microheterogeneity 775:796 Cell fractionation using a Percoll gradient and deglycosylation with PNGase F were performed to analyze the possible basis of DPP-IV and FAP microheterogeneity. 28452380 8 50 theme glioblastoma 1340:1351 arg1 tissues 1353:1359 glioblastoma tissues 1340:1359 glioblastoma tissues 1340:1359 In glioma cell lines in vitro, several isoforms of both enzymes were expressed, however the alkalic forms present in glioblastoma tissues were not detected. 28452380 0 51 theme peptidase-IV 47:58 arg1 forms 27:31 molecular forms 17:31 molecular forms of dipeptidyl peptidase-IV and fibroblast activation protein 17:92 Heterogeneity of molecular forms of dipeptidyl peptidase-IV and fibroblast activation protein in human glioblastomas. 28452380 10 52 from tissue 1621:1626 arg1 present 1597:1603 present 1597:1603 present 1597:1603 CONCLUSION Several isoforms of DPP-IV and FAP are present in glioblastoma tissue. 28452380 4 53 theme WB 561:562 arg1 assay 582:586 WB or enzyme overlay assay 561:586 assay 582:586 METHODS ELISA, isoelectric focusing, 1D and 2D electrophoresis followed by WB or enzyme overlay assay were utilized to analyze DPP-IV and FAP isoforms. 28452380 11 54 theme cell 1688:1691 arg1 lines 1693:1697 glioma cell lines 1681:1697 glioma cell lines 1681:1697 The absence of alkaline isoforms of both enzymes in glioma cell lines however suggests that isoforms from other, most likely stromal, cell types contribute to the overall pattern seen in glioblastoma tissues. 28452380 7 55 theme glioblastoma 1201:1212 arg1 tissues 1214:1220 glioblastoma tissues 1201:1220 glioblastoma tissues 1201:1220 Using 2D electrophoresis, two to three molecular forms of FAP with an alkaline (7.0-8.5) pI and an estimated MW of 120-140 kDa were identified in glioblastoma tissues. 28452380 11 56 theme isoforms 1653:1660 arg1 absence 1633:1639 The absence 1629:1639 The absence of alkaline isoforms of both enzymes in glioma cell lines 1629:1697 The absence of alkaline isoforms of both enzymes in glioma cell lines however suggests that isoforms from other, most likely stromal, cell types contribute to the overall pattern seen in glioblastoma tissues. 28452380 5 57 theme Percoll 665:671 arg1 gradient 673:680 a Percoll gradient 663:680 a Percoll gradient 663:680 Cell fractionation using a Percoll gradient and deglycosylation with PNGase F were performed to analyze the possible basis of DPP-IV and FAP microheterogeneity. 28452380 6 58 theme human 927:931 arg1 glioblastoma 933:944 human glioblastoma 927:944 human glioblastoma 927:944 RESULTS Molecular forms of DPP-IV with an estimated molecular weight of 140-160 kDa and a pI predominantly 5.8 were detected in human glioblastoma; in some tumors additional isoforms with a more acidic (3.5-5.5) as well as alkaline (8.1) pI were revealed. 28452380 10 59 located present 1597:1603 arg1 tissue 1621:1626 glioblastoma tissue 1608:1626 glioblastoma tissue 1608:1626 CONCLUSION Several isoforms of DPP-IV and FAP are present in glioblastoma tissue. 28452380 10 59 located present 1597:1603 arg2 isoforms 1566:1573 CONCLUSION Several isoforms 1547:1573 CONCLUSION Several isoforms of DPP-IV and FAP 1547:1591 CONCLUSION Several isoforms of DPP-IV and FAP are present in glioblastoma tissue. 28452380 5 60 with gradient 673:680 arg1 F 714:714 PNGase F 707:714 PNGase F 707:714 Cell fractionation using a Percoll gradient and deglycosylation with PNGase F were performed to analyze the possible basis of DPP-IV and FAP microheterogeneity. 28452380 11 61 theme overall 1792:1798 arg1 pattern 1800:1806 the overall pattern 1788:1806 the overall pattern seen in glioblastoma tissues 1788:1835 The absence of alkaline isoforms of both enzymes in glioma cell lines however suggests that isoforms from other, most likely stromal, cell types contribute to the overall pattern seen in glioblastoma tissues. 28452380 7 62 with FAP 1113:1115 arg1 pI 1144:1145 an alkaline (7.0-8.5) pI 1122:1145 an alkaline (7.0-8.5) pI 1122:1145 Using 2D electrophoresis, two to three molecular forms of FAP with an alkaline (7.0-8.5) pI and an estimated MW of 120-140 kDa were identified in glioblastoma tissues. 28452380 5 63 theme Cell 638:641 arg1 fractionation 643:655 Cell fractionation 638:655 Cell fractionation using a Percoll gradient and deglycosylation with PNGase F 638:714 Cell fractionation using a Percoll gradient and deglycosylation with PNGase F were performed to analyze the possible basis of DPP-IV and FAP microheterogeneity. 28452380 6 64 theme DPP-IV 826:831 arg1 forms 817:821 Molecular forms 807:821 RESULTS Molecular forms of DPP-IV with an estimated molecular weight of 140-160 kDa and a pI predominantly 5.8 799:908 RESULTS Molecular forms of DPP-IV with an estimated molecular weight of 140-160 kDa and a pI predominantly 5.8 were detected in human glioblastoma; in some tumors additional isoforms with a more acidic (3.5-5.5) as well as alkaline (8.1) pI were revealed. 28452380 7 65 theme FAP 1113:1115 arg1 MW 1164:1165 an estimated MW 1151:1165 an estimated MW of 120-140 kDa 1151:1180 Using 2D electrophoresis, two to three molecular forms of FAP with an alkaline (7.0-8.5) pI and an estimated MW of 120-140 kDa were identified in glioblastoma tissues. 28452380 7 65 theme FAP 1113:1115 arg1 forms 1104:1108 two to three molecular forms 1081:1108 two to three molecular forms of FAP with an alkaline (7.0-8.5) pI 1081:1145 Using 2D electrophoresis, two to three molecular forms of FAP with an alkaline (7.0-8.5) pI and an estimated MW of 120-140 kDa were identified in glioblastoma tissues. 28452380 6 66 with DPP-IV 826:831 arg1 weight 861:866 an estimated molecular weight 838:866 an estimated molecular weight of 140-160 kDa and a pI predominantly 5.8 838:908 RESULTS Molecular forms of DPP-IV with an estimated molecular weight of 140-160 kDa and a pI predominantly 5.8 were detected in human glioblastoma; in some tumors additional isoforms with a more acidic (3.5-5.5) as well as alkaline (8.1) pI were revealed. 28452380 6 67 located detected 915:922 arg2 RESULTS 799:805 RESULTS 799:805 RESULTS Molecular forms of DPP-IV with an estimated molecular weight of 140-160 kDa and a pI predominantly 5.8 799:908 RESULTS Molecular forms of DPP-IV with an estimated molecular weight of 140-160 kDa and a pI predominantly 5.8 were detected in human glioblastoma; in some tumors additional isoforms with a more acidic (3.5-5.5) as well as alkaline (8.1) pI were revealed. 28452380 6 67 located detected 915:922 arg1 glioblastoma 933:944 human glioblastoma 927:944 human glioblastoma 927:944 RESULTS Molecular forms of DPP-IV with an estimated molecular weight of 140-160 kDa and a pI predominantly 5.8 were detected in human glioblastoma; in some tumors additional isoforms with a more acidic (3.5-5.5) as well as alkaline (8.1) pI were revealed. 28452380 7 68 theme 2D 1061:1062 arg1 electrophoresis 1064:1078 2D electrophoresis 1061:1078 2D electrophoresis 1061:1078 Using 2D electrophoresis, two to three molecular forms of FAP with an alkaline (7.0-8.5) pI and an estimated MW of 120-140 kDa were identified in glioblastoma tissues. 28452380 2 69 theme fibroblast 346:355 arg1 FAP 377:379 FAP 377:379 FAP 377:379 We previously reported increased expression of the proline specific peptidases dipeptidyl peptidase-IV (DPP-IV) and its closest paralogue fibroblast activation protein (FAP) in human glioblastomas. 28452380 2 69 theme fibroblast 346:355 arg1 protein 368:374 fibroblast activation protein 346:374 its closest paralogue fibroblast activation protein (FAP) 324:380 We previously reported increased expression of the proline specific peptidases dipeptidyl peptidase-IV (DPP-IV) and its closest paralogue fibroblast activation protein (FAP) in human glioblastomas. 28452380 1 70 theme cancers 199:205 arg1 progression 176:186 the progression 172:186 the progression of various cancers 172:205 BACKGROUND AND AIMS Proteolytic enzymes contribute to the progression of various cancers. 28452380 11 71 theme glioma 1681:1686 arg1 lines 1693:1697 glioma cell lines 1681:1697 glioma cell lines 1681:1697 The absence of alkaline isoforms of both enzymes in glioma cell lines however suggests that isoforms from other, most likely stromal, cell types contribute to the overall pattern seen in glioblastoma tissues. 28452380 10 72 theme Several 1558:1564 arg1 isoforms 1566:1573 CONCLUSION Several isoforms 1547:1573 CONCLUSION Several isoforms of DPP-IV and FAP 1547:1591 CONCLUSION Several isoforms of DPP-IV and FAP are present in glioblastoma tissue. 28452380 2 73 theme closest 328:334 arg1 peptidases 276:285 the proline specific peptidases 255:285 the proline specific peptidases dipeptidyl peptidase-IV (DPP-IV) and its closest paralogue fibroblast activation protein (FAP) 255:380 We previously reported increased expression of the proline specific peptidases dipeptidyl peptidase-IV (DPP-IV) and its closest paralogue fibroblast activation protein (FAP) in human glioblastomas. 28452380 2 73 theme closest 328:334 arg1 paralogue 336:344 its closest paralogue fibroblast activation protein (FAP) 324:380 its closest paralogue fibroblast activation protein (FAP) 324:380 We previously reported increased expression of the proline specific peptidases dipeptidyl peptidase-IV (DPP-IV) and its closest paralogue fibroblast activation protein (FAP) in human glioblastomas. 28452380 9 74 theme oligosaccharides 1400:1415 arg1 Removal 1380:1386 Removal 1380:1386 Removal of N-linked oligosaccharides 1380:1415 Removal of N-linked oligosaccharides decreased the estimated molecular weight of both enzymes; the overall pattern of molecular forms nevertheless remained unchanged. 28452380 2 75 theme proline 259:265 arg1 peptidases 276:285 the proline specific peptidases 255:285 the proline specific peptidases dipeptidyl peptidase-IV (DPP-IV) and its closest paralogue fibroblast activation protein (FAP) 255:380 We previously reported increased expression of the proline specific peptidases dipeptidyl peptidase-IV (DPP-IV) and its closest paralogue fibroblast activation protein (FAP) in human glioblastomas. 28452380 2 75 theme proline 259:265 arg1 paralogue 336:344 its closest paralogue fibroblast activation protein (FAP) 324:380 its closest paralogue fibroblast activation protein (FAP) 324:380 We previously reported increased expression of the proline specific peptidases dipeptidyl peptidase-IV (DPP-IV) and its closest paralogue fibroblast activation protein (FAP) in human glioblastomas. 28452380 2 75 theme proline 259:265 arg1 peptidase-IV 298:309 dipeptidyl peptidase-IV 287:309 dipeptidyl peptidase-IV (DPP-IV) 287:318 We previously reported increased expression of the proline specific peptidases dipeptidyl peptidase-IV (DPP-IV) and its closest paralogue fibroblast activation protein (FAP) in human glioblastomas. 28452380 8 76 from tissues 1353:1359 arg1 present 1329:1335 present 1329:1335 present 1329:1335 In glioma cell lines in vitro, several isoforms of both enzymes were expressed, however the alkalic forms present in glioblastoma tissues were not detected. 28452380 6 77 theme additional 962:971 arg1 isoforms 973:980 additional isoforms 962:980 additional isoforms with a more acidic (3.5-5.5) as well as alkaline (8.1) pI 962:1038 RESULTS Molecular forms of DPP-IV with an estimated molecular weight of 140-160 kDa and a pI predominantly 5.8 were detected in human glioblastoma; in some tumors additional isoforms with a more acidic (3.5-5.5) as well as alkaline (8.1) pI were revealed. 28452380 9 78 theme molecular 1441:1449 arg1 weight 1451:1456 the estimated molecular weight 1427:1456 the estimated molecular weight of both enzymes 1427:1472 Removal of N-linked oligosaccharides decreased the estimated molecular weight of both enzymes; the overall pattern of molecular forms nevertheless remained unchanged. 28452380 4 79 theme 2D 530:531 arg1 METHODS 486:492 METHODS ELISA, isoelectric focusing, 1D and 2D electrophoresis 486:547 METHODS ELISA, isoelectric focusing, 1D and 2D electrophoresis followed by WB or enzyme overlay assay 486:586 METHODS ELISA, isoelectric focusing, 1D and 2D electrophoresis followed by WB or enzyme overlay assay were utilized to analyze DPP-IV and FAP isoforms. 28452380 4 79 theme 2D 530:531 arg1 electrophoresis 533:547 2D electrophoresis 530:547 2D electrophoresis 530:547 METHODS ELISA, isoelectric focusing, 1D and 2D electrophoresis followed by WB or enzyme overlay assay were utilized to analyze DPP-IV and FAP isoforms. 28452380 8 80 theme cell 1233:1236 arg1 lines 1238:1242 glioma cell lines 1226:1242 glioma cell lines in vitro 1226:1251 In glioma cell lines in vitro, several isoforms of both enzymes were expressed, however the alkalic forms present in glioblastoma tissues were not detected. 28452380 4 81 used utilized 593:600 arg2 ELISA 494:498 ELISA 494:498 ELISA 494:498 METHODS ELISA, isoelectric focusing, 1D and 2D electrophoresis followed by WB or enzyme overlay assay were utilized to analyze DPP-IV and FAP isoforms. 28452380 4 81 used utilized 593:600 arg2 electrophoresis 533:547 2D electrophoresis 530:547 2D electrophoresis 530:547 METHODS ELISA, isoelectric focusing, 1D and 2D electrophoresis followed by WB or enzyme overlay assay were utilized to analyze DPP-IV and FAP isoforms. 28452380 4 81 used utilized 593:600 arg2 METHODS 486:492 METHODS ELISA, isoelectric focusing, 1D and 2D electrophoresis 486:547 METHODS ELISA, isoelectric focusing, 1D and 2D electrophoresis followed by WB or enzyme overlay assay 486:586 METHODS ELISA, isoelectric focusing, 1D and 2D electrophoresis followed by WB or enzyme overlay assay were utilized to analyze DPP-IV and FAP isoforms. 28452380 4 81 used utilized 593:600 arg2 1D 523:524 1D 523:524 1D 523:524 METHODS ELISA, isoelectric focusing, 1D and 2D electrophoresis followed by WB or enzyme overlay assay were utilized to analyze DPP-IV and FAP isoforms. 28452380 1 82 theme Proteolytic 138:148 arg1 enzymes 150:156 BACKGROUND AND AIMS Proteolytic enzymes 118:156 BACKGROUND AND AIMS Proteolytic enzymes 118:156 BACKGROUND AND AIMS Proteolytic enzymes contribute to the progression of various cancers. 28452380 6 83 theme alkaline 1022:1029 arg1 pI 1037:1038 alkaline (8.1) pI 1022:1038 a more acidic (3.5-5.5) as well as alkaline (8.1) pI 987:1038 RESULTS Molecular forms of DPP-IV with an estimated molecular weight of 140-160 kDa and a pI predominantly 5.8 were detected in human glioblastoma; in some tumors additional isoforms with a more acidic (3.5-5.5) as well as alkaline (8.1) pI were revealed. 28452380 11 84 from types 1768:1772 arg1 isoforms 1721:1728 isoforms 1721:1728 isoforms from other, most likely stromal, cell types 1721:1772 The absence of alkaline isoforms of both enzymes in glioma cell lines however suggests that isoforms from other, most likely stromal, cell types contribute to the overall pattern seen in glioblastoma tissues. 28452380 2 85 dep paralogue 336:344 arg1 FAP 377:379 FAP 377:379 FAP 377:379 We previously reported increased expression of the proline specific peptidases dipeptidyl peptidase-IV (DPP-IV) and its closest paralogue fibroblast activation protein (FAP) in human glioblastomas. 28452380 2 85 dep paralogue 336:344 arg1 protein 368:374 fibroblast activation protein 346:374 its closest paralogue fibroblast activation protein (FAP) 324:380 We previously reported increased expression of the proline specific peptidases dipeptidyl peptidase-IV (DPP-IV) and its closest paralogue fibroblast activation protein (FAP) in human glioblastomas. 28452380 0 86 theme activation 75:84 arg1 protein 86:92 fibroblast activation protein 64:92 fibroblast activation protein 64:92 Heterogeneity of molecular forms of dipeptidyl peptidase-IV and fibroblast activation protein in human glioblastomas. 28452380 2 87 theme peptidases 276:285 arg1 expression 241:250 increased expression 231:250 increased expression of the proline specific peptidases dipeptidyl peptidase-IV (DPP-IV) and its closest paralogue fibroblast activation protein (FAP) in human glioblastomas 231:403 We previously reported increased expression of the proline specific peptidases dipeptidyl peptidase-IV (DPP-IV) and its closest paralogue fibroblast activation protein (FAP) in human glioblastomas. 28452380 9 88 theme enzymes 1466:1472 arg1 weight 1451:1456 the estimated molecular weight 1427:1456 the estimated molecular weight of both enzymes 1427:1472 Removal of N-linked oligosaccharides decreased the estimated molecular weight of both enzymes; the overall pattern of molecular forms nevertheless remained unchanged. 28452380 7 89 theme estimated 1154:1162 arg1 MW 1164:1165 an estimated MW 1151:1165 an estimated MW of 120-140 kDa 1151:1180 Using 2D electrophoresis, two to three molecular forms of FAP with an alkaline (7.0-8.5) pI and an estimated MW of 120-140 kDa were identified in glioblastoma tissues. 28452380 5 90 theme microheterogeneity 779:796 arg1 basis 755:759 the possible basis 742:759 the possible basis of DPP-IV and FAP microheterogeneity 742:796 Cell fractionation using a Percoll gradient and deglycosylation with PNGase F were performed to analyze the possible basis of DPP-IV and FAP microheterogeneity. 28452380 5 91 theme possible 746:753 arg1 basis 755:759 the possible basis 742:759 the possible basis of DPP-IV and FAP microheterogeneity 742:796 Cell fractionation using a Percoll gradient and deglycosylation with PNGase F were performed to analyze the possible basis of DPP-IV and FAP microheterogeneity. 28452380 2 92 theme activation 357:366 arg1 FAP 377:379 FAP 377:379 FAP 377:379 We previously reported increased expression of the proline specific peptidases dipeptidyl peptidase-IV (DPP-IV) and its closest paralogue fibroblast activation protein (FAP) in human glioblastomas. 28452380 2 92 theme activation 357:366 arg1 protein 368:374 fibroblast activation protein 346:374 its closest paralogue fibroblast activation protein (FAP) 324:380 We previously reported increased expression of the proline specific peptidases dipeptidyl peptidase-IV (DPP-IV) and its closest paralogue fibroblast activation protein (FAP) in human glioblastomas. 28452380 9 93 theme molecular 1498:1506 arg1 forms 1508:1512 molecular forms 1498:1512 molecular forms 1498:1512 Removal of N-linked oligosaccharides decreased the estimated molecular weight of both enzymes; the overall pattern of molecular forms nevertheless remained unchanged. 28452380 2 94 from expression 241:250 arg1 glioblastomas 391:403 human glioblastomas 385:403 human glioblastomas 385:403 We previously reported increased expression of the proline specific peptidases dipeptidyl peptidase-IV (DPP-IV) and its closest paralogue fibroblast activation protein (FAP) in human glioblastomas. 28452380 10 95 theme glioblastoma 1608:1619 arg1 tissue 1621:1626 glioblastoma tissue 1608:1626 glioblastoma tissue 1608:1626 CONCLUSION Several isoforms of DPP-IV and FAP are present in glioblastoma tissue. 28452380 4 96 theme overlay 574:580 arg1 assay 582:586 WB or enzyme overlay assay 561:586 assay 582:586 METHODS ELISA, isoelectric focusing, 1D and 2D electrophoresis followed by WB or enzyme overlay assay were utilized to analyze DPP-IV and FAP isoforms. 28452380 0 97 theme forms 27:31 arg1 Heterogeneity 0:12 Heterogeneity 0:12 Heterogeneity of molecular forms of dipeptidyl peptidase-IV and fibroblast activation protein in human glioblastomas. 0:116 Heterogeneity of molecular forms of dipeptidyl peptidase-IV and fibroblast activation protein in human glioblastomas. 28452380 4 98 dep focusing 513:520 arg1 isoelectric 501:511 isoelectric 501:511 isoelectric 501:511 METHODS ELISA, isoelectric focusing, 1D and 2D electrophoresis followed by WB or enzyme overlay assay were utilized to analyze DPP-IV and FAP isoforms. 28452380 7 99 theme molecular 1094:1102 arg1 forms 1104:1108 two to three molecular forms 1081:1108 two to three molecular forms of FAP with an alkaline (7.0-8.5) pI 1081:1145 Using 2D electrophoresis, two to three molecular forms of FAP with an alkaline (7.0-8.5) pI and an estimated MW of 120-140 kDa were identified in glioblastoma tissues. 28452380 0 100 theme dipeptidyl 36:45 arg1 peptidase-IV 47:58 dipeptidyl peptidase-IV 36:58 dipeptidyl peptidase-IV 36:58 Heterogeneity of molecular forms of dipeptidyl peptidase-IV and fibroblast activation protein in human glioblastomas. 28452380 0 101 gly Heterogeneity 0:12 arg1 forms 27:31 molecular forms 17:31 molecular forms of dipeptidyl peptidase-IV and fibroblast activation protein 17:92 Heterogeneity of molecular forms of dipeptidyl peptidase-IV and fibroblast activation protein in human glioblastomas. 28452380 6 102 theme 8.1 1032:1034 arg1 pI 1037:1038 alkaline (8.1) pI 1022:1038 a more acidic (3.5-5.5) as well as alkaline (8.1) pI 987:1038 RESULTS Molecular forms of DPP-IV with an estimated molecular weight of 140-160 kDa and a pI predominantly 5.8 were detected in human glioblastoma; in some tumors additional isoforms with a more acidic (3.5-5.5) as well as alkaline (8.1) pI were revealed. 28452380 11 103 theme alkaline 1644:1651 arg1 isoforms 1653:1660 alkaline isoforms 1644:1660 alkaline isoforms of both enzymes 1644:1676 The absence of alkaline isoforms of both enzymes in glioma cell lines however suggests that isoforms from other, most likely stromal, cell types contribute to the overall pattern seen in glioblastoma tissues. 28452380 6 104 theme kDa 879:881 arg1 weight 861:866 an estimated molecular weight 838:866 an estimated molecular weight of 140-160 kDa and a pI predominantly 5.8 838:908 RESULTS Molecular forms of DPP-IV with an estimated molecular weight of 140-160 kDa and a pI predominantly 5.8 were detected in human glioblastoma; in some tumors additional isoforms with a more acidic (3.5-5.5) as well as alkaline (8.1) pI were revealed. 28452380 10 105 from present 1597:1603 arg1 tissue 1621:1626 glioblastoma tissue 1608:1626 glioblastoma tissue 1608:1626 CONCLUSION Several isoforms of DPP-IV and FAP are present in glioblastoma tissue. 28452380 3 106 theme molecular 426:434 arg1 heterogeneity 436:448 the molecular heterogeneity 422:448 the molecular heterogeneity of DPP-IV and FAP in glioblastomas 422:483 Here we analyze the molecular heterogeneity of DPP-IV and FAP in glioblastomas. 28452380 2 107 theme increased 231:239 arg1 expression 241:250 increased expression 231:250 increased expression of the proline specific peptidases dipeptidyl peptidase-IV (DPP-IV) and its closest paralogue fibroblast activation protein (FAP) in human glioblastomas 231:403 We previously reported increased expression of the proline specific peptidases dipeptidyl peptidase-IV (DPP-IV) and its closest paralogue fibroblast activation protein (FAP) in human glioblastomas. 28452380 4 108 theme FAP 624:626 arg1 isoforms 628:635 DPP-IV and FAP isoforms 613:635 isoforms 628:635 METHODS ELISA, isoelectric focusing, 1D and 2D electrophoresis followed by WB or enzyme overlay assay were utilized to analyze DPP-IV and FAP isoforms. 28452380 11 109 theme enzymes 1670:1676 arg1 isoforms 1653:1660 alkaline isoforms 1644:1660 alkaline isoforms of both enzymes 1644:1676 The absence of alkaline isoforms of both enzymes in glioma cell lines however suggests that isoforms from other, most likely stromal, cell types contribute to the overall pattern seen in glioblastoma tissues. 28452380 5 110 with deglycosylation 686:700 arg1 F 714:714 PNGase F 707:714 PNGase F 707:714 Cell fractionation using a Percoll gradient and deglycosylation with PNGase F were performed to analyze the possible basis of DPP-IV and FAP microheterogeneity. 28452380 6 111 theme molecular 851:859 arg1 weight 861:866 an estimated molecular weight 838:866 an estimated molecular weight of 140-160 kDa and a pI predominantly 5.8 838:908 RESULTS Molecular forms of DPP-IV with an estimated molecular weight of 140-160 kDa and a pI predominantly 5.8 were detected in human glioblastoma; in some tumors additional isoforms with a more acidic (3.5-5.5) as well as alkaline (8.1) pI were revealed. 28452380 2 112 theme human 385:389 arg1 glioblastomas 391:403 human glioblastomas 385:403 human glioblastomas 385:403 We previously reported increased expression of the proline specific peptidases dipeptidyl peptidase-IV (DPP-IV) and its closest paralogue fibroblast activation protein (FAP) in human glioblastomas. 28280335 2 0 theme proteomic 477:485 arg1 approach 487:494 a quantitative proteomic approach 462:494 a quantitative proteomic approach 462:494 To further understand the molecular mechanisms that produce this superior drug efficacy of Abr, a quantitative proteomic approach has been applied to investigate the global protein expression profiles of lung cancer cell A549 treated with Abr and PTX. 28280335 2 1 dep cancer 575:580 arg1 A549 587:590 cell A549 582:590 lung cancer cell A549 treated with Abr and PTX 570:615 To further understand the molecular mechanisms that produce this superior drug efficacy of Abr, a quantitative proteomic approach has been applied to investigate the global protein expression profiles of lung cancer cell A549 treated with Abr and PTX. 28280335 7 2 theme insulin 1370:1376 arg1 secretion 1378:1386 insulin secretion 1370:1386 insulin secretion which correlates with type 2 diabetes 1370:1424 It is also noteworthy that the deficiency of GNA1 might reduce insulin secretion which correlates with type 2 diabetes. 28280335 6 3 theme GNA1 1242:1245 arg1 downregulation 1224:1237 the downregulation 1220:1237 the downregulation 1220:1237 In summary, this study first shows that the superior drug effect of Abr is mainly due to the downregulation of GNA1, which causes proliferative delay and cell adhesion defect. 28280335 4 4 theme several 999:1005 arg1 functions 1017:1025 several important functions 999:1025 several important functions such as embryonic development and growth 999:1066 GNA1 is a key enzyme in the biosynthesis of uridine diphosphate-N-acetylglucosamine, which is an important donor substrate for N-linked glycosylation and has several important functions such as embryonic development and growth. 28280335 4 4 theme several 999:1005 arg1 growth 1061:1066 growth 1061:1066 growth 1061:1066 GNA1 is a key enzyme in the biosynthesis of uridine diphosphate-N-acetylglucosamine, which is an important donor substrate for N-linked glycosylation and has several important functions such as embryonic development and growth. 28280335 4 4 theme several 999:1005 arg1 development 1045:1055 development 1045:1055 development 1045:1055 GNA1 is a key enzyme in the biosynthesis of uridine diphosphate-N-acetylglucosamine, which is an important donor substrate for N-linked glycosylation and has several important functions such as embryonic development and growth. 28280335 2 5 theme quantitative 464:475 arg1 approach 487:494 a quantitative proteomic approach 462:494 a quantitative proteomic approach 462:494 To further understand the molecular mechanisms that produce this superior drug efficacy of Abr, a quantitative proteomic approach has been applied to investigate the global protein expression profiles of lung cancer cell A549 treated with Abr and PTX. 28280335 4 6 link N-linked 968:975 arg1 glycosylation 977:989 N-linked glycosylation 968:989 N-linked glycosylation 968:989 GNA1 is a key enzyme in the biosynthesis of uridine diphosphate-N-acetylglucosamine, which is an important donor substrate for N-linked glycosylation and has several important functions such as embryonic development and growth. 28280335 0 7 theme glucosamine 99:109 arg1 6-phosphate 111:121 glucosamine 6-phosphate N-acetyltransferase 1 (GNPNAT1/GNA1) 99:158 glucosamine 6-phosphate N-acetyltransferase 1 (GNPNAT1/GNA1) 99:158 Nanoparticle abraxane possesses impaired proliferation in A549 cells due to the underexpression of glucosamine 6-phosphate N-acetyltransferase 1 (GNPNAT1/GNA1). 28280335 7 8 theme GNA1 1352:1355 arg1 deficiency 1338:1347 the deficiency 1334:1347 the deficiency of GNA1 1334:1355 It is also noteworthy that the deficiency of GNA1 might reduce insulin secretion which correlates with type 2 diabetes. 28280335 4 9 theme uridine 885:891 arg1 diphosphate-N-acetylglucosamine 893:923 uridine diphosphate-N-acetylglucosamine 885:923 uridine diphosphate-N-acetylglucosamine 885:923 GNA1 is a key enzyme in the biosynthesis of uridine diphosphate-N-acetylglucosamine, which is an important donor substrate for N-linked glycosylation and has several important functions such as embryonic development and growth. 28280335 6 10 theme cell 1285:1288 arg1 defect 1299:1304 proliferative delay and cell adhesion defect 1261:1304 defect 1299:1304 In summary, this study first shows that the superior drug effect of Abr is mainly due to the downregulation of GNA1, which causes proliferative delay and cell adhesion defect. 28280335 2 11 theme cell 582:585 arg1 A549 587:590 cell A549 582:590 lung cancer cell A549 treated with Abr and PTX 570:615 To further understand the molecular mechanisms that produce this superior drug efficacy of Abr, a quantitative proteomic approach has been applied to investigate the global protein expression profiles of lung cancer cell A549 treated with Abr and PTX. 28280335 0 12 dep 6-phosphate 111:121 arg1 GNPNAT1/GNA1 146:157 GNPNAT1/GNA1 146:157 GNPNAT1/GNA1 146:157 Nanoparticle abraxane possesses impaired proliferation in A549 cells due to the underexpression of glucosamine 6-phosphate N-acetyltransferase 1 (GNPNAT1/GNA1). 28280335 0 12 dep 6-phosphate 111:121 arg1 N-acetyltransferase 123:141 N-acetyltransferase 1 123:143 glucosamine 6-phosphate N-acetyltransferase 1 (GNPNAT1/GNA1) 99:158 Nanoparticle abraxane possesses impaired proliferation in A549 cells due to the underexpression of glucosamine 6-phosphate N-acetyltransferase 1 (GNPNAT1/GNA1). 28280335 2 13 theme superior 431:438 arg1 efficacy 445:452 this superior drug efficacy 426:452 this superior drug efficacy of Abr 426:459 To further understand the molecular mechanisms that produce this superior drug efficacy of Abr, a quantitative proteomic approach has been applied to investigate the global protein expression profiles of lung cancer cell A549 treated with Abr and PTX. 28280335 1 14 theme non-small-cell 276:289 arg1 cancer 296:301 non-small-cell lung cancer 276:301 non-small-cell lung cancer 276:301 Abraxane (Abr), a US Food and Drug Administration-approved albumin-bound nanoparticle applied for the treatment of non-small-cell lung cancer, has been reported to be more effective than paclitaxel (PTX). 28280335 4 15 theme diphosphate-N-acetylglucosamine 893:923 arg1 biosynthesis 869:880 the biosynthesis 865:880 the biosynthesis of uridine diphosphate-N-acetylglucosamine 865:923 GNA1 is a key enzyme in the biosynthesis of uridine diphosphate-N-acetylglucosamine, which is an important donor substrate for N-linked glycosylation and has several important functions such as embryonic development and growth. 28280335 3 16 theme significant 705:715 arg1 P<0.05 742:747 P<0.05 742:747 P<0.05 742:747 Only one protein, namely, glucosamine 6-phosphate N-acetyltransferase 1 (GNA1), showed significant differential expression (P<0.05) in the cutoff of 2.0 fold, suggesting that Abr can be used safely as a substitute for PTX. 28280335 3 16 theme significant 705:715 arg1 expression 730:739 significant differential expression 705:739 significant differential expression (P<0.05) 705:748 Only one protein, namely, glucosamine 6-phosphate N-acetyltransferase 1 (GNA1), showed significant differential expression (P<0.05) in the cutoff of 2.0 fold, suggesting that Abr can be used safely as a substitute for PTX. 28280335 6 17 theme Abr 1199:1201 arg1 due 1213:1215 due 1213:1215 due 1213:1215 In summary, this study first shows that the superior drug effect of Abr is mainly due to the downregulation of GNA1, which causes proliferative delay and cell adhesion defect. 28280335 6 17 theme Abr 1199:1201 arg1 effect 1189:1194 the superior drug effect 1171:1194 the superior drug effect of Abr 1171:1201 In summary, this study first shows that the superior drug effect of Abr is mainly due to the downregulation of GNA1, which causes proliferative delay and cell adhesion defect. 28280335 3 18 dep 6-phosphate 656:666 arg1 N-acetyltransferase 668:686 N-acetyltransferase 1 668:688 glucosamine 6-phosphate N-acetyltransferase 1 (GNA1) 644:695 Only one protein, namely, glucosamine 6-phosphate N-acetyltransferase 1 (GNA1), showed significant differential expression (P<0.05) in the cutoff of 2.0 fold, suggesting that Abr can be used safely as a substitute for PTX. 28280335 3 18 dep 6-phosphate 656:666 arg1 GNA1 691:694 GNA1 691:694 GNA1 691:694 Only one protein, namely, glucosamine 6-phosphate N-acetyltransferase 1 (GNA1), showed significant differential expression (P<0.05) in the cutoff of 2.0 fold, suggesting that Abr can be used safely as a substitute for PTX. 28280335 4 19 theme key 851:853 arg1 substrate 954:962 an important donor substrate 935:962 an important donor substrate for N-linked glycosylation 935:989 GNA1 is a key enzyme in the biosynthesis of uridine diphosphate-N-acetylglucosamine, which is an important donor substrate for N-linked glycosylation and has several important functions such as embryonic development and growth. 28280335 4 19 theme key 851:853 arg1 enzyme 855:860 a key enzyme 849:860 a key enzyme 849:860 GNA1 is a key enzyme in the biosynthesis of uridine diphosphate-N-acetylglucosamine, which is an important donor substrate for N-linked glycosylation and has several important functions such as embryonic development and growth. 28280335 4 19 theme key 851:853 arg1 GNA1 841:844 GNA1 841:844 GNA1 841:844 GNA1 is a key enzyme in the biosynthesis of uridine diphosphate-N-acetylglucosamine, which is an important donor substrate for N-linked glycosylation and has several important functions such as embryonic development and growth. 28280335 0 20 theme 6-phosphate 111:121 arg1 underexpression 80:94 the underexpression 76:94 the underexpression of glucosamine 6-phosphate N-acetyltransferase 1 (GNPNAT1/GNA1) 76:158 Nanoparticle abraxane possesses impaired proliferation in A549 cells due to the underexpression of glucosamine 6-phosphate N-acetyltransferase 1 (GNPNAT1/GNA1). 28280335 5 21 theme major 1085:1089 arg1 role 1091:1094 a major role 1083:1094 a major role 1083:1094 Albumin plays a major role in the regulation of this protein. 28280335 0 22 contain possesses 22:30 arg1 abraxane 13:20 Nanoparticle abraxane 0:20 Nanoparticle abraxane 0:20 Nanoparticle abraxane possesses impaired proliferation in A549 cells due to the underexpression of glucosamine 6-phosphate N-acetyltransferase 1 (GNPNAT1/GNA1). 28280335 0 22 contain possesses 22:30 arg2 proliferation 41:53 impaired proliferation 32:53 impaired proliferation in A549 cells 32:67 Nanoparticle abraxane possesses impaired proliferation in A549 cells due to the underexpression of glucosamine 6-phosphate N-acetyltransferase 1 (GNPNAT1/GNA1). 28280335 0 23 theme Nanoparticle 0:11 arg1 abraxane 13:20 Nanoparticle abraxane 0:20 Nanoparticle abraxane 0:20 Nanoparticle abraxane possesses impaired proliferation in A549 cells due to the underexpression of glucosamine 6-phosphate N-acetyltransferase 1 (GNPNAT1/GNA1). 28280335 6 24 theme proliferative 1261:1273 arg1 delay 1275:1279 proliferative delay and cell adhesion defect 1261:1304 delay 1275:1279 In summary, this study first shows that the superior drug effect of Abr is mainly due to the downregulation of GNA1, which causes proliferative delay and cell adhesion defect. 28280335 0 25 from proliferation 41:53 arg1 cells 63:67 A549 cells 58:67 A549 cells 58:67 Nanoparticle abraxane possesses impaired proliferation in A549 cells due to the underexpression of glucosamine 6-phosphate N-acetyltransferase 1 (GNPNAT1/GNA1). 28280335 4 26 contain has 995:997 arg1 substrate 954:962 an important donor substrate 935:962 an important donor substrate for N-linked glycosylation 935:989 GNA1 is a key enzyme in the biosynthesis of uridine diphosphate-N-acetylglucosamine, which is an important donor substrate for N-linked glycosylation and has several important functions such as embryonic development and growth. 28280335 4 26 contain has 995:997 arg1 enzyme 855:860 a key enzyme 849:860 a key enzyme 849:860 GNA1 is a key enzyme in the biosynthesis of uridine diphosphate-N-acetylglucosamine, which is an important donor substrate for N-linked glycosylation and has several important functions such as embryonic development and growth. 28280335 4 26 contain has 995:997 arg2 growth 1061:1066 growth 1061:1066 growth 1061:1066 GNA1 is a key enzyme in the biosynthesis of uridine diphosphate-N-acetylglucosamine, which is an important donor substrate for N-linked glycosylation and has several important functions such as embryonic development and growth. 28280335 4 26 contain has 995:997 arg2 development 1045:1055 development 1045:1055 development 1045:1055 GNA1 is a key enzyme in the biosynthesis of uridine diphosphate-N-acetylglucosamine, which is an important donor substrate for N-linked glycosylation and has several important functions such as embryonic development and growth. 28280335 4 26 contain has 995:997 arg1 GNA1 841:844 GNA1 841:844 GNA1 841:844 GNA1 is a key enzyme in the biosynthesis of uridine diphosphate-N-acetylglucosamine, which is an important donor substrate for N-linked glycosylation and has several important functions such as embryonic development and growth. 28280335 4 26 contain has 995:997 arg2 functions 1017:1025 several important functions 999:1025 several important functions such as embryonic development and growth 999:1066 GNA1 is a key enzyme in the biosynthesis of uridine diphosphate-N-acetylglucosamine, which is an important donor substrate for N-linked glycosylation and has several important functions such as embryonic development and growth. 28280335 2 27 theme drug 440:443 arg1 efficacy 445:452 this superior drug efficacy 426:452 this superior drug efficacy of Abr 426:459 To further understand the molecular mechanisms that produce this superior drug efficacy of Abr, a quantitative proteomic approach has been applied to investigate the global protein expression profiles of lung cancer cell A549 treated with Abr and PTX. 28280335 1 28 theme lung 291:294 arg1 cancer 296:301 non-small-cell lung cancer 276:301 non-small-cell lung cancer 276:301 Abraxane (Abr), a US Food and Drug Administration-approved albumin-bound nanoparticle applied for the treatment of non-small-cell lung cancer, has been reported to be more effective than paclitaxel (PTX). 28280335 6 29 theme drug 1184:1187 arg1 due 1213:1215 due 1213:1215 due 1213:1215 In summary, this study first shows that the superior drug effect of Abr is mainly due to the downregulation of GNA1, which causes proliferative delay and cell adhesion defect. 28280335 6 29 theme drug 1184:1187 arg1 effect 1189:1194 the superior drug effect 1171:1194 the superior drug effect of Abr 1171:1201 In summary, this study first shows that the superior drug effect of Abr is mainly due to the downregulation of GNA1, which causes proliferative delay and cell adhesion defect. 28280335 4 30 theme N-linked 968:975 arg1 glycosylation 977:989 N-linked glycosylation 968:989 N-linked glycosylation 968:989 GNA1 is a key enzyme in the biosynthesis of uridine diphosphate-N-acetylglucosamine, which is an important donor substrate for N-linked glycosylation and has several important functions such as embryonic development and growth. 28280335 0 31 theme impaired 32:39 arg1 proliferation 41:53 impaired proliferation 32:53 impaired proliferation in A549 cells 32:67 Nanoparticle abraxane possesses impaired proliferation in A549 cells due to the underexpression of glucosamine 6-phosphate N-acetyltransferase 1 (GNPNAT1/GNA1). 28280335 1 32 theme cancer 296:301 arg1 treatment 263:271 the treatment 259:271 the treatment of non-small-cell lung cancer 259:301 Abraxane (Abr), a US Food and Drug Administration-approved albumin-bound nanoparticle applied for the treatment of non-small-cell lung cancer, has been reported to be more effective than paclitaxel (PTX). 28280335 2 33 theme expression 547:556 arg1 profiles 558:565 the global protein expression profiles 528:565 the global protein expression profiles of lung cancer cell A549 treated with Abr and PTX 528:615 To further understand the molecular mechanisms that produce this superior drug efficacy of Abr, a quantitative proteomic approach has been applied to investigate the global protein expression profiles of lung cancer cell A549 treated with Abr and PTX. 28280335 3 34 theme differential 717:728 arg1 P<0.05 742:747 P<0.05 742:747 P<0.05 742:747 Only one protein, namely, glucosamine 6-phosphate N-acetyltransferase 1 (GNA1), showed significant differential expression (P<0.05) in the cutoff of 2.0 fold, suggesting that Abr can be used safely as a substitute for PTX. 28280335 3 34 theme differential 717:728 arg1 expression 730:739 significant differential expression 705:739 significant differential expression (P<0.05) 705:748 Only one protein, namely, glucosamine 6-phosphate N-acetyltransferase 1 (GNA1), showed significant differential expression (P<0.05) in the cutoff of 2.0 fold, suggesting that Abr can be used safely as a substitute for PTX. 28280335 2 35 theme protein 539:545 arg1 profiles 558:565 the global protein expression profiles 528:565 the global protein expression profiles of lung cancer cell A549 treated with Abr and PTX 528:615 To further understand the molecular mechanisms that produce this superior drug efficacy of Abr, a quantitative proteomic approach has been applied to investigate the global protein expression profiles of lung cancer cell A549 treated with Abr and PTX. 28280335 4 36 theme donor 948:952 arg1 substrate 954:962 an important donor substrate 935:962 an important donor substrate for N-linked glycosylation 935:989 GNA1 is a key enzyme in the biosynthesis of uridine diphosphate-N-acetylglucosamine, which is an important donor substrate for N-linked glycosylation and has several important functions such as embryonic development and growth. 28280335 4 36 theme donor 948:952 arg1 enzyme 855:860 a key enzyme 849:860 a key enzyme 849:860 GNA1 is a key enzyme in the biosynthesis of uridine diphosphate-N-acetylglucosamine, which is an important donor substrate for N-linked glycosylation and has several important functions such as embryonic development and growth. 28280335 4 36 theme donor 948:952 arg1 GNA1 841:844 GNA1 841:844 GNA1 841:844 GNA1 is a key enzyme in the biosynthesis of uridine diphosphate-N-acetylglucosamine, which is an important donor substrate for N-linked glycosylation and has several important functions such as embryonic development and growth. 28280335 2 37 theme global 532:537 arg1 profiles 558:565 the global protein expression profiles 528:565 the global protein expression profiles of lung cancer cell A549 treated with Abr and PTX 528:615 To further understand the molecular mechanisms that produce this superior drug efficacy of Abr, a quantitative proteomic approach has been applied to investigate the global protein expression profiles of lung cancer cell A549 treated with Abr and PTX. 28280335 6 38 theme superior 1175:1182 arg1 due 1213:1215 due 1213:1215 due 1213:1215 In summary, this study first shows that the superior drug effect of Abr is mainly due to the downregulation of GNA1, which causes proliferative delay and cell adhesion defect. 28280335 6 38 theme superior 1175:1182 arg1 effect 1189:1194 the superior drug effect 1171:1194 the superior drug effect of Abr 1171:1201 In summary, this study first shows that the superior drug effect of Abr is mainly due to the downregulation of GNA1, which causes proliferative delay and cell adhesion defect. 28280335 4 39 theme important 938:946 arg1 substrate 954:962 an important donor substrate 935:962 an important donor substrate for N-linked glycosylation 935:989 GNA1 is a key enzyme in the biosynthesis of uridine diphosphate-N-acetylglucosamine, which is an important donor substrate for N-linked glycosylation and has several important functions such as embryonic development and growth. 28280335 4 39 theme important 938:946 arg1 enzyme 855:860 a key enzyme 849:860 a key enzyme 849:860 GNA1 is a key enzyme in the biosynthesis of uridine diphosphate-N-acetylglucosamine, which is an important donor substrate for N-linked glycosylation and has several important functions such as embryonic development and growth. 28280335 4 39 theme important 938:946 arg1 GNA1 841:844 GNA1 841:844 GNA1 841:844 GNA1 is a key enzyme in the biosynthesis of uridine diphosphate-N-acetylglucosamine, which is an important donor substrate for N-linked glycosylation and has several important functions such as embryonic development and growth. 28280335 4 40 from enzyme 855:860 arg1 biosynthesis 869:880 the biosynthesis 865:880 the biosynthesis of uridine diphosphate-N-acetylglucosamine 865:923 GNA1 is a key enzyme in the biosynthesis of uridine diphosphate-N-acetylglucosamine, which is an important donor substrate for N-linked glycosylation and has several important functions such as embryonic development and growth. 28280335 1 41 dep US 179:180 arg1 Drug 191:194 Drug 191:194 Drug 191:194 Abraxane (Abr), a US Food and Drug Administration-approved albumin-bound nanoparticle applied for the treatment of non-small-cell lung cancer, has been reported to be more effective than paclitaxel (PTX). 28280335 1 41 dep US 179:180 arg1 Food 182:185 Food 182:185 Food 182:185 Abraxane (Abr), a US Food and Drug Administration-approved albumin-bound nanoparticle applied for the treatment of non-small-cell lung cancer, has been reported to be more effective than paclitaxel (PTX). 28280335 3 42 used used 804:807 arg2 Abr 793:795 Abr 793:795 Abr 793:795 Only one protein, namely, glucosamine 6-phosphate N-acetyltransferase 1 (GNA1), showed significant differential expression (P<0.05) in the cutoff of 2.0 fold, suggesting that Abr can be used safely as a substitute for PTX. 28280335 3 42 used used 804:807 arg2 a 819:819 a 819:819 a 819:819 Only one protein, namely, glucosamine 6-phosphate N-acetyltransferase 1 (GNA1), showed significant differential expression (P<0.05) in the cutoff of 2.0 fold, suggesting that Abr can be used safely as a substitute for PTX. 28280335 1 43 theme Administration-approved 196:218 arg1 nanoparticle 234:245 Administration-approved albumin-bound nanoparticle 196:245 Administration-approved albumin-bound nanoparticle 196:245 Abraxane (Abr), a US Food and Drug Administration-approved albumin-bound nanoparticle applied for the treatment of non-small-cell lung cancer, has been reported to be more effective than paclitaxel (PTX). 28280335 2 44 theme Abr 457:459 arg1 efficacy 445:452 this superior drug efficacy 426:452 this superior drug efficacy of Abr 426:459 To further understand the molecular mechanisms that produce this superior drug efficacy of Abr, a quantitative proteomic approach has been applied to investigate the global protein expression profiles of lung cancer cell A549 treated with Abr and PTX. 28280335 6 45 theme adhesion 1290:1297 arg1 defect 1299:1304 proliferative delay and cell adhesion defect 1261:1304 defect 1299:1304 In summary, this study first shows that the superior drug effect of Abr is mainly due to the downregulation of GNA1, which causes proliferative delay and cell adhesion defect. 28280335 2 46 theme cancer 575:580 arg1 profiles 558:565 the global protein expression profiles 528:565 the global protein expression profiles of lung cancer cell A549 treated with Abr and PTX 528:615 To further understand the molecular mechanisms that produce this superior drug efficacy of Abr, a quantitative proteomic approach has been applied to investigate the global protein expression profiles of lung cancer cell A549 treated with Abr and PTX. 28280335 0 47 theme A549 58:61 arg1 cells 63:67 A549 cells 58:67 A549 cells 58:67 Nanoparticle abraxane possesses impaired proliferation in A549 cells due to the underexpression of glucosamine 6-phosphate N-acetyltransferase 1 (GNPNAT1/GNA1). 28280335 2 48 theme lung 570:573 arg1 cancer 575:580 lung cancer cell A549 treated with Abr and PTX 570:615 lung cancer cell A549 treated with Abr and PTX 570:615 To further understand the molecular mechanisms that produce this superior drug efficacy of Abr, a quantitative proteomic approach has been applied to investigate the global protein expression profiles of lung cancer cell A549 treated with Abr and PTX. 28280335 3 49 theme glucosamine 644:654 arg1 protein 627:633 Only one protein 618:633 Only one protein 618:633 Only one protein, namely, glucosamine 6-phosphate N-acetyltransferase 1 (GNA1), showed significant differential expression (P<0.05) in the cutoff of 2.0 fold, suggesting that Abr can be used safely as a substitute for PTX. 28280335 3 49 theme glucosamine 644:654 arg1 6-phosphate 656:666 glucosamine 6-phosphate N-acetyltransferase 1 (GNA1) 644:695 glucosamine 6-phosphate N-acetyltransferase 1 (GNA1) 644:695 Only one protein, namely, glucosamine 6-phosphate N-acetyltransferase 1 (GNA1), showed significant differential expression (P<0.05) in the cutoff of 2.0 fold, suggesting that Abr can be used safely as a substitute for PTX. 28280335 4 50 theme embryonic 1035:1043 arg1 development 1045:1055 development 1045:1055 development 1045:1055 GNA1 is a key enzyme in the biosynthesis of uridine diphosphate-N-acetylglucosamine, which is an important donor substrate for N-linked glycosylation and has several important functions such as embryonic development and growth. 28280335 3 51 dep a 819:819 arg1 substitute 821:830 substitute 821:830 substitute for PTX 821:838 Only one protein, namely, glucosamine 6-phosphate N-acetyltransferase 1 (GNA1), showed significant differential expression (P<0.05) in the cutoff of 2.0 fold, suggesting that Abr can be used safely as a substitute for PTX. 28280335 1 52 theme albumin-bound 220:232 arg1 nanoparticle 234:245 Administration-approved albumin-bound nanoparticle 196:245 Administration-approved albumin-bound nanoparticle 196:245 Abraxane (Abr), a US Food and Drug Administration-approved albumin-bound nanoparticle applied for the treatment of non-small-cell lung cancer, has been reported to be more effective than paclitaxel (PTX). 28280335 2 53 theme molecular 392:400 arg1 mechanisms 402:411 the molecular mechanisms 388:411 the molecular mechanisms that produce this superior drug efficacy of Abr 388:459 To further understand the molecular mechanisms that produce this superior drug efficacy of Abr, a quantitative proteomic approach has been applied to investigate the global protein expression profiles of lung cancer cell A549 treated with Abr and PTX. 28280335 1 54 dep Food 182:185 arg1 nanoparticle 234:245 Administration-approved albumin-bound nanoparticle 196:245 Administration-approved albumin-bound nanoparticle 196:245 Abraxane (Abr), a US Food and Drug Administration-approved albumin-bound nanoparticle applied for the treatment of non-small-cell lung cancer, has been reported to be more effective than paclitaxel (PTX). 28280335 5 55 theme protein 1122:1128 arg1 regulation 1103:1112 the regulation 1099:1112 the regulation of this protein 1099:1128 Albumin plays a major role in the regulation of this protein. 28280335 7 56 theme type 1410:1413 arg1 diabetes 1417:1424 type 2 diabetes 1410:1424 type 2 diabetes 1410:1424 It is also noteworthy that the deficiency of GNA1 might reduce insulin secretion which correlates with type 2 diabetes. 28280335 3 57 theme fold 771:774 arg1 cutoff 757:762 the cutoff 753:762 the cutoff of 2.0 fold 753:774 Only one protein, namely, glucosamine 6-phosphate N-acetyltransferase 1 (GNA1), showed significant differential expression (P<0.05) in the cutoff of 2.0 fold, suggesting that Abr can be used safely as a substitute for PTX. 28280335 4 58 theme important 1007:1015 arg1 functions 1017:1025 several important functions 999:1025 several important functions such as embryonic development and growth 999:1066 GNA1 is a key enzyme in the biosynthesis of uridine diphosphate-N-acetylglucosamine, which is an important donor substrate for N-linked glycosylation and has several important functions such as embryonic development and growth. 28280335 4 58 theme important 1007:1015 arg1 growth 1061:1066 growth 1061:1066 growth 1061:1066 GNA1 is a key enzyme in the biosynthesis of uridine diphosphate-N-acetylglucosamine, which is an important donor substrate for N-linked glycosylation and has several important functions such as embryonic development and growth. 28280335 4 58 theme important 1007:1015 arg1 development 1045:1055 development 1045:1055 development 1045:1055 GNA1 is a key enzyme in the biosynthesis of uridine diphosphate-N-acetylglucosamine, which is an important donor substrate for N-linked glycosylation and has several important functions such as embryonic development and growth. 26497208 7 0 theme additional 1294:1303 arg1 pathways 1316:1323 additional processing pathways 1294:1323 additional processing pathways 1294:1323 Characterization of the extracellular expression of CDCP1 identified novel circulating forms and revealed that extracellular vesicles provide additional processing pathways. 26497208 4 1 theme metastatic 602:611 arg1 potential 613:621 the metastatic potential 598:621 the metastatic potential of syngeneic cell models 598:646 The relative expression of full-length CDCP1 correlated with the metastatic potential of syngeneic cell models and an increase in surface membrane expression of CDCP1 was observed in tumor compared to adjacent normal prostate tissues. 26497208 5 2 dep level 914:918 arg1 the 899:901 the 899:901 the 899:901 We demonstrated that glycosylation of CDCP1 is a prerequisite for protein stability and plasma membrane localization, and that the expression level and extent of N-glycosylation of CDCP1 correlated with metastatic status. 26497208 2 3 theme outside-in 288:297 arg1 signaling 309:317 outside-in oncogenic signaling 288:317 outside-in oncogenic signaling 288:317 Given that proteolytic cleavage of the ectodomain correlates with outside-in oncogenic signaling, we characterized glycosylation in the context of cellular processing and expression of CDCP1 in prostate cancer. 26497208 9 4 theme surface 1520:1526 arg1 presentation 1528:1539 cell surface presentation 1515:1539 cell surface presentation 1515:1539 Our results establish that differential glycosylation, cell surface presentation and extracellular expression of CDCP1 are hallmarks of PCa progression. 26497208 9 4 theme surface 1520:1526 arg1 expression 1559:1568 extracellular expression 1545:1568 extracellular expression of CDCP1 1545:1577 Our results establish that differential glycosylation, cell surface presentation and extracellular expression of CDCP1 are hallmarks of PCa progression. 26497208 9 4 theme surface 1520:1526 arg1 glycosylation 1500:1512 differential glycosylation 1487:1512 differential glycosylation 1487:1512 Our results establish that differential glycosylation, cell surface presentation and extracellular expression of CDCP1 are hallmarks of PCa progression. 26497208 9 4 theme surface 1520:1526 arg1 hallmarks 1583:1591 hallmarks 1583:1591 hallmarks of PCa progression 1583:1610 Our results establish that differential glycosylation, cell surface presentation and extracellular expression of CDCP1 are hallmarks of PCa progression. 26497208 4 5 theme surface 667:673 arg1 expression 684:693 surface membrane expression 667:693 surface membrane expression of CDCP1 667:702 The relative expression of full-length CDCP1 correlated with the metastatic potential of syngeneic cell models and an increase in surface membrane expression of CDCP1 was observed in tumor compared to adjacent normal prostate tissues. 26497208 7 6 theme novel 1221:1225 arg1 forms 1239:1243 novel circulating forms 1221:1243 novel circulating forms 1221:1243 Characterization of the extracellular expression of CDCP1 identified novel circulating forms and revealed that extracellular vesicles provide additional processing pathways. 26497208 4 7 from increase 655:662 arg1 expression 684:693 surface membrane expression 667:693 surface membrane expression of CDCP1 667:702 The relative expression of full-length CDCP1 correlated with the metastatic potential of syngeneic cell models and an increase in surface membrane expression of CDCP1 was observed in tumor compared to adjacent normal prostate tissues. 26497208 1 8 theme potent 181:186 arg1 function 202:209 a potent pro-migratory function 179:209 a potent pro-migratory function in tumors 179:219 CUB-domain-containing protein 1 (CDCP1) is a trans-membrane protein regulator of cell adhesion with a potent pro-migratory function in tumors. 26497208 2 9 from processing 378:387 arg1 cancer 425:430 prostate cancer 416:430 prostate cancer 416:430 Given that proteolytic cleavage of the ectodomain correlates with outside-in oncogenic signaling, we characterized glycosylation in the context of cellular processing and expression of CDCP1 in prostate cancer. 26497208 8 10 theme immunoaffinity 1336:1349 arg1 spectrometry 1356:1367 immunoaffinity mass spectrometry 1336:1367 immunoaffinity mass spectrometry 1336:1367 Employing immunoaffinity mass spectrometry, we detected elevated levels of circulating CDCP1 in patient urine with high-risk disease. 26497208 8 11 theme high-risk 1441:1449 arg1 disease 1451:1457 high-risk disease 1441:1457 high-risk disease 1441:1457 Employing immunoaffinity mass spectrometry, we detected elevated levels of circulating CDCP1 in patient urine with high-risk disease. 26497208 9 12 theme CDCP1 1573:1577 arg1 presentation 1528:1539 cell surface presentation 1515:1539 cell surface presentation 1515:1539 Our results establish that differential glycosylation, cell surface presentation and extracellular expression of CDCP1 are hallmarks of PCa progression. 26497208 9 12 theme CDCP1 1573:1577 arg1 expression 1559:1568 extracellular expression 1545:1568 extracellular expression of CDCP1 1545:1577 Our results establish that differential glycosylation, cell surface presentation and extracellular expression of CDCP1 are hallmarks of PCa progression. 26497208 9 12 theme CDCP1 1573:1577 arg1 glycosylation 1500:1512 differential glycosylation 1487:1512 differential glycosylation 1487:1512 Our results establish that differential glycosylation, cell surface presentation and extracellular expression of CDCP1 are hallmarks of PCa progression. 26497208 9 12 theme CDCP1 1573:1577 arg1 hallmarks 1583:1591 hallmarks 1583:1591 hallmarks of PCa progression 1583:1610 Our results establish that differential glycosylation, cell surface presentation and extracellular expression of CDCP1 are hallmarks of PCa progression. 26497208 5 13 theme membrane 867:874 arg1 localization 876:887 plasma membrane localization 860:887 plasma membrane localization 860:887 We demonstrated that glycosylation of CDCP1 is a prerequisite for protein stability and plasma membrane localization, and that the expression level and extent of N-glycosylation of CDCP1 correlated with metastatic status. 26497208 9 14 theme PCa 1596:1598 arg1 progression 1600:1610 PCa progression 1596:1610 PCa progression 1596:1610 Our results establish that differential glycosylation, cell surface presentation and extracellular expression of CDCP1 are hallmarks of PCa progression. 26497208 8 15 theme elevated 1382:1389 arg1 levels 1391:1396 elevated levels 1382:1396 elevated levels of circulating CDCP1 1382:1417 Employing immunoaffinity mass spectrometry, we detected elevated levels of circulating CDCP1 in patient urine with high-risk disease. 26497208 1 16 theme trans-membrane 124:137 arg1 regulator 147:155 a trans-membrane protein regulator 122:155 a trans-membrane protein regulator of cell adhesion with a potent pro-migratory function in tumors 122:219 CUB-domain-containing protein 1 (CDCP1) is a trans-membrane protein regulator of cell adhesion with a potent pro-migratory function in tumors. 26497208 1 16 theme trans-membrane 124:137 arg1 protein 101:107 CUB-domain-containing protein 1 79:109 CUB-domain-containing protein 1 (CDCP1) 79:117 CUB-domain-containing protein 1 (CDCP1) is a trans-membrane protein regulator of cell adhesion with a potent pro-migratory function in tumors. 26497208 9 17 theme progression 1600:1610 arg1 presentation 1528:1539 cell surface presentation 1515:1539 cell surface presentation 1515:1539 Our results establish that differential glycosylation, cell surface presentation and extracellular expression of CDCP1 are hallmarks of PCa progression. 26497208 9 17 theme progression 1600:1610 arg1 expression 1559:1568 extracellular expression 1545:1568 extracellular expression of CDCP1 1545:1577 Our results establish that differential glycosylation, cell surface presentation and extracellular expression of CDCP1 are hallmarks of PCa progression. 26497208 9 17 theme progression 1600:1610 arg1 glycosylation 1500:1512 differential glycosylation 1487:1512 differential glycosylation 1487:1512 Our results establish that differential glycosylation, cell surface presentation and extracellular expression of CDCP1 are hallmarks of PCa progression. 26497208 9 17 theme progression 1600:1610 arg1 hallmarks 1583:1591 hallmarks 1583:1591 hallmarks of PCa progression 1583:1610 Our results establish that differential glycosylation, cell surface presentation and extracellular expression of CDCP1 are hallmarks of PCa progression. 26497208 4 18 theme CDCP1 698:702 arg1 expression 684:693 surface membrane expression 667:693 surface membrane expression of CDCP1 667:702 The relative expression of full-length CDCP1 correlated with the metastatic potential of syngeneic cell models and an increase in surface membrane expression of CDCP1 was observed in tumor compared to adjacent normal prostate tissues. 26497208 0 19 theme prostate 62:69 arg1 cancer 71:76 prostate cancer 62:76 prostate cancer 62:76 Dysregulated expression of cell surface glycoprotein CDCP1 in prostate cancer. 26497208 5 20 theme protein 838:844 arg1 stability 846:854 protein stability 838:854 protein stability 838:854 We demonstrated that glycosylation of CDCP1 is a prerequisite for protein stability and plasma membrane localization, and that the expression level and extent of N-glycosylation of CDCP1 correlated with metastatic status. 26497208 5 21 theme expression 903:912 arg1 level 914:918 expression level 903:918 expression level 903:918 We demonstrated that glycosylation of CDCP1 is a prerequisite for protein stability and plasma membrane localization, and that the expression level and extent of N-glycosylation of CDCP1 correlated with metastatic status. 26497208 6 22 theme sialic 1039:1044 arg1 chains 1051:1056 sialic acid chains 1039:1056 sialic acid chains 1039:1056 Interestingly, complex N-linked glycans with sialic acid chains were restricted to the N-terminal half of the ectodomain and absent in the truncated species. 26497208 8 23 theme CDCP1 1413:1417 arg1 levels 1391:1396 elevated levels 1382:1396 elevated levels of circulating CDCP1 1382:1417 Employing immunoaffinity mass spectrometry, we detected elevated levels of circulating CDCP1 in patient urine with high-risk disease. 26497208 7 24 theme extracellular 1263:1275 arg1 vesicles 1277:1284 extracellular vesicles 1263:1284 extracellular vesicles 1263:1284 Characterization of the extracellular expression of CDCP1 identified novel circulating forms and revealed that extracellular vesicles provide additional processing pathways. 26497208 1 25 theme cell 160:163 arg1 adhesion 165:172 cell adhesion 160:172 cell adhesion 160:172 CUB-domain-containing protein 1 (CDCP1) is a trans-membrane protein regulator of cell adhesion with a potent pro-migratory function in tumors. 26497208 8 26 theme patient 1422:1428 arg1 urine 1430:1434 patient urine 1422:1434 patient urine with high-risk disease 1422:1457 Employing immunoaffinity mass spectrometry, we detected elevated levels of circulating CDCP1 in patient urine with high-risk disease. 26497208 1 27 with regulator 147:155 arg1 function 202:209 a potent pro-migratory function 179:209 a potent pro-migratory function in tumors 179:219 CUB-domain-containing protein 1 (CDCP1) is a trans-membrane protein regulator of cell adhesion with a potent pro-migratory function in tumors. 26497208 6 28 theme complex 1009:1015 arg1 glycans 1026:1032 complex N-linked glycans 1009:1032 complex N-linked glycans with sialic acid chains 1009:1056 Interestingly, complex N-linked glycans with sialic acid chains were restricted to the N-terminal half of the ectodomain and absent in the truncated species. 26497208 0 29 theme glycoprotein 40:51 arg1 expression 13:22 Dysregulated expression 0:22 Dysregulated expression of cell surface glycoprotein 0:51 Dysregulated expression of cell surface glycoprotein CDCP1 in prostate cancer. 26497208 1 30 theme CUB-domain-containing 79:99 arg1 regulator 147:155 a trans-membrane protein regulator 122:155 a trans-membrane protein regulator of cell adhesion with a potent pro-migratory function in tumors 122:219 CUB-domain-containing protein 1 (CDCP1) is a trans-membrane protein regulator of cell adhesion with a potent pro-migratory function in tumors. 26497208 1 30 theme CUB-domain-containing 79:99 arg1 protein 101:107 CUB-domain-containing protein 1 79:109 CUB-domain-containing protein 1 (CDCP1) 79:117 CUB-domain-containing protein 1 (CDCP1) is a trans-membrane protein regulator of cell adhesion with a potent pro-migratory function in tumors. 26497208 1 30 theme CUB-domain-containing 79:99 arg1 CDCP1 112:116 CDCP1 112:116 CDCP1 112:116 CUB-domain-containing protein 1 (CDCP1) is a trans-membrane protein regulator of cell adhesion with a potent pro-migratory function in tumors. 26497208 4 31 located observed 708:715 arg1 tumor 720:724 tumor 720:724 tumor 720:724 The relative expression of full-length CDCP1 correlated with the metastatic potential of syngeneic cell models and an increase in surface membrane expression of CDCP1 was observed in tumor compared to adjacent normal prostate tissues. 26497208 4 31 located observed 708:715 arg2 increase 655:662 an increase 652:662 an increase in surface membrane expression of CDCP1 652:702 The relative expression of full-length CDCP1 correlated with the metastatic potential of syngeneic cell models and an increase in surface membrane expression of CDCP1 was observed in tumor compared to adjacent normal prostate tissues. 26497208 4 32 theme normal 747:752 arg1 tissues 763:769 adjacent normal prostate tissues 738:769 adjacent normal prostate tissues 738:769 The relative expression of full-length CDCP1 correlated with the metastatic potential of syngeneic cell models and an increase in surface membrane expression of CDCP1 was observed in tumor compared to adjacent normal prostate tissues. 26497208 0 33 theme Dysregulated 0:11 arg1 expression 13:22 Dysregulated expression 0:22 Dysregulated expression of cell surface glycoprotein 0:51 Dysregulated expression of cell surface glycoprotein CDCP1 in prostate cancer. 26497208 3 34 theme processed 481:489 arg1 species 498:504 135 kDa full-length and proteolytic processed 70 kDa species 445:504 135 kDa full-length and proteolytic processed 70 kDa species 445:504 We detected 135 kDa full-length and proteolytic processed 70 kDa species in a panel of PCa cell models. 26497208 7 35 theme CDCP1 1204:1208 arg1 expression 1190:1199 the extracellular expression 1172:1199 the extracellular expression of CDCP1 1172:1208 Characterization of the extracellular expression of CDCP1 identified novel circulating forms and revealed that extracellular vesicles provide additional processing pathways. 26497208 5 36 theme metastatic 975:984 arg1 status 986:991 metastatic status 975:991 metastatic status 975:991 We demonstrated that glycosylation of CDCP1 is a prerequisite for protein stability and plasma membrane localization, and that the expression level and extent of N-glycosylation of CDCP1 correlated with metastatic status. 26497208 4 37 theme full-length 564:574 arg1 CDCP1 576:580 full-length CDCP1 564:580 full-length CDCP1 564:580 The relative expression of full-length CDCP1 correlated with the metastatic potential of syngeneic cell models and an increase in surface membrane expression of CDCP1 was observed in tumor compared to adjacent normal prostate tissues. 26497208 7 38 theme expression 1190:1199 arg1 Characterization 1152:1167 Characterization 1152:1167 Characterization of the extracellular expression of CDCP1 1152:1208 Characterization of the extracellular expression of CDCP1 identified novel circulating forms and revealed that extracellular vesicles provide additional processing pathways. 26497208 0 39 theme surface 32:38 arg1 glycoprotein 40:51 cell surface glycoprotein 27:51 cell surface glycoprotein 27:51 Dysregulated expression of cell surface glycoprotein CDCP1 in prostate cancer. 26497208 2 40 gly glycosylation 337:349 arg1 context 358:364 the context 354:364 the context of cellular processing and expression of CDCP1 in prostate cancer 354:430 Given that proteolytic cleavage of the ectodomain correlates with outside-in oncogenic signaling, we characterized glycosylation in the context of cellular processing and expression of CDCP1 in prostate cancer. 26497208 3 41 theme kDa 494:496 arg1 species 498:504 135 kDa full-length and proteolytic processed 70 kDa species 445:504 135 kDa full-length and proteolytic processed 70 kDa species 445:504 We detected 135 kDa full-length and proteolytic processed 70 kDa species in a panel of PCa cell models. 26497208 0 42 gly glycoprotein 40:51 arg1 glycoprotein 40:51 cell surface glycoprotein 27:51 cell surface glycoprotein 27:51 Dysregulated expression of cell surface glycoprotein CDCP1 in prostate cancer. 26497208 2 43 from cancer 425:430 arg1 context 358:364 the context 354:364 the context of cellular processing and expression of CDCP1 in prostate cancer 354:430 Given that proteolytic cleavage of the ectodomain correlates with outside-in oncogenic signaling, we characterized glycosylation in the context of cellular processing and expression of CDCP1 in prostate cancer. 26497208 6 44 theme truncated 1133:1141 arg1 species 1143:1149 the truncated species 1129:1149 the truncated species 1129:1149 Interestingly, complex N-linked glycans with sialic acid chains were restricted to the N-terminal half of the ectodomain and absent in the truncated species. 26497208 3 45 theme proteolytic 469:479 arg1 kDa 449:451 135 kDa 445:451 135 kDa full-length and proteolytic 445:479 We detected 135 kDa full-length and proteolytic processed 70 kDa species in a panel of PCa cell models. 26497208 3 46 theme PCa 520:522 arg1 models 529:534 PCa cell models 520:534 PCa cell models 520:534 We detected 135 kDa full-length and proteolytic processed 70 kDa species in a panel of PCa cell models. 26497208 4 47 theme syngeneic 626:634 arg1 models 641:646 syngeneic cell models 626:646 syngeneic cell models 626:646 The relative expression of full-length CDCP1 correlated with the metastatic potential of syngeneic cell models and an increase in surface membrane expression of CDCP1 was observed in tumor compared to adjacent normal prostate tissues. 26497208 2 48 theme cellular 369:376 arg1 processing 378:387 cellular processing 369:387 cellular processing 369:387 Given that proteolytic cleavage of the ectodomain correlates with outside-in oncogenic signaling, we characterized glycosylation in the context of cellular processing and expression of CDCP1 in prostate cancer. 26497208 7 49 theme processing 1305:1314 arg1 pathways 1316:1323 additional processing pathways 1294:1323 additional processing pathways 1294:1323 Characterization of the extracellular expression of CDCP1 identified novel circulating forms and revealed that extracellular vesicles provide additional processing pathways. 26497208 2 50 theme oncogenic 299:307 arg1 signaling 309:317 outside-in oncogenic signaling 288:317 outside-in oncogenic signaling 288:317 Given that proteolytic cleavage of the ectodomain correlates with outside-in oncogenic signaling, we characterized glycosylation in the context of cellular processing and expression of CDCP1 in prostate cancer. 26497208 9 51 theme cell 1515:1518 arg1 presentation 1528:1539 cell surface presentation 1515:1539 cell surface presentation 1515:1539 Our results establish that differential glycosylation, cell surface presentation and extracellular expression of CDCP1 are hallmarks of PCa progression. 26497208 9 51 theme cell 1515:1518 arg1 expression 1559:1568 extracellular expression 1545:1568 extracellular expression of CDCP1 1545:1577 Our results establish that differential glycosylation, cell surface presentation and extracellular expression of CDCP1 are hallmarks of PCa progression. 26497208 9 51 theme cell 1515:1518 arg1 glycosylation 1500:1512 differential glycosylation 1487:1512 differential glycosylation 1487:1512 Our results establish that differential glycosylation, cell surface presentation and extracellular expression of CDCP1 are hallmarks of PCa progression. 26497208 9 51 theme cell 1515:1518 arg1 hallmarks 1583:1591 hallmarks 1583:1591 hallmarks of PCa progression 1583:1610 Our results establish that differential glycosylation, cell surface presentation and extracellular expression of CDCP1 are hallmarks of PCa progression. 26497208 2 52 from context 358:364 arg1 cancer 425:430 prostate cancer 416:430 prostate cancer 416:430 Given that proteolytic cleavage of the ectodomain correlates with outside-in oncogenic signaling, we characterized glycosylation in the context of cellular processing and expression of CDCP1 in prostate cancer. 26497208 3 53 theme models 529:534 arg1 panel 511:515 a panel 509:515 a panel of PCa cell models 509:534 We detected 135 kDa full-length and proteolytic processed 70 kDa species in a panel of PCa cell models. 26497208 1 54 theme adhesion 165:172 arg1 regulator 147:155 a trans-membrane protein regulator 122:155 a trans-membrane protein regulator of cell adhesion with a potent pro-migratory function in tumors 122:219 CUB-domain-containing protein 1 (CDCP1) is a trans-membrane protein regulator of cell adhesion with a potent pro-migratory function in tumors. 26497208 1 54 theme adhesion 165:172 arg1 protein 101:107 CUB-domain-containing protein 1 79:109 CUB-domain-containing protein 1 (CDCP1) 79:117 CUB-domain-containing protein 1 (CDCP1) is a trans-membrane protein regulator of cell adhesion with a potent pro-migratory function in tumors. 26497208 6 55 link N-linked 1017:1024 arg1 glycans 1026:1032 complex N-linked glycans 1009:1032 complex N-linked glycans with sialic acid chains 1009:1056 Interestingly, complex N-linked glycans with sialic acid chains were restricted to the N-terminal half of the ectodomain and absent in the truncated species. 26497208 9 56 theme extracellular 1545:1557 arg1 presentation 1528:1539 cell surface presentation 1515:1539 cell surface presentation 1515:1539 Our results establish that differential glycosylation, cell surface presentation and extracellular expression of CDCP1 are hallmarks of PCa progression. 26497208 9 56 theme extracellular 1545:1557 arg1 expression 1559:1568 extracellular expression 1545:1568 extracellular expression of CDCP1 1545:1577 Our results establish that differential glycosylation, cell surface presentation and extracellular expression of CDCP1 are hallmarks of PCa progression. 26497208 9 56 theme extracellular 1545:1557 arg1 glycosylation 1500:1512 differential glycosylation 1487:1512 differential glycosylation 1487:1512 Our results establish that differential glycosylation, cell surface presentation and extracellular expression of CDCP1 are hallmarks of PCa progression. 26497208 9 56 theme extracellular 1545:1557 arg1 hallmarks 1583:1591 hallmarks 1583:1591 hallmarks of PCa progression 1583:1610 Our results establish that differential glycosylation, cell surface presentation and extracellular expression of CDCP1 are hallmarks of PCa progression. 26497208 4 57 theme membrane 675:682 arg1 expression 684:693 surface membrane expression 667:693 surface membrane expression of CDCP1 667:702 The relative expression of full-length CDCP1 correlated with the metastatic potential of syngeneic cell models and an increase in surface membrane expression of CDCP1 was observed in tumor compared to adjacent normal prostate tissues. 26497208 1 58 theme pro-migratory 188:200 arg1 function 202:209 a potent pro-migratory function 179:209 a potent pro-migratory function in tumors 179:219 CUB-domain-containing protein 1 (CDCP1) is a trans-membrane protein regulator of cell adhesion with a potent pro-migratory function in tumors. 26497208 4 59 theme models 641:646 arg1 potential 613:621 the metastatic potential 598:621 the metastatic potential of syngeneic cell models 598:646 The relative expression of full-length CDCP1 correlated with the metastatic potential of syngeneic cell models and an increase in surface membrane expression of CDCP1 was observed in tumor compared to adjacent normal prostate tissues. 26497208 2 60 theme proteolytic 233:243 arg1 cleavage 245:252 proteolytic cleavage 233:252 proteolytic cleavage of the ectodomain 233:270 Given that proteolytic cleavage of the ectodomain correlates with outside-in oncogenic signaling, we characterized glycosylation in the context of cellular processing and expression of CDCP1 in prostate cancer. 26497208 5 61 theme plasma 860:865 arg1 localization 876:887 plasma membrane localization 860:887 plasma membrane localization 860:887 We demonstrated that glycosylation of CDCP1 is a prerequisite for protein stability and plasma membrane localization, and that the expression level and extent of N-glycosylation of CDCP1 correlated with metastatic status. 26497208 5 62 gly N-glycosylation 934:948 arg1 CDCP1 953:957 CDCP1 953:957 CDCP1 953:957 We demonstrated that glycosylation of CDCP1 is a prerequisite for protein stability and plasma membrane localization, and that the expression level and extent of N-glycosylation of CDCP1 correlated with metastatic status. 26497208 8 63 theme mass 1351:1354 arg1 spectrometry 1356:1367 immunoaffinity mass spectrometry 1336:1367 immunoaffinity mass spectrometry 1336:1367 Employing immunoaffinity mass spectrometry, we detected elevated levels of circulating CDCP1 in patient urine with high-risk disease. 26497208 2 64 theme ectodomain 261:270 arg1 cleavage 245:252 proteolytic cleavage 233:252 proteolytic cleavage of the ectodomain 233:270 Given that proteolytic cleavage of the ectodomain correlates with outside-in oncogenic signaling, we characterized glycosylation in the context of cellular processing and expression of CDCP1 in prostate cancer. 26497208 1 65 from function 202:209 arg1 tumors 214:219 tumors 214:219 tumors 214:219 CUB-domain-containing protein 1 (CDCP1) is a trans-membrane protein regulator of cell adhesion with a potent pro-migratory function in tumors. 26497208 5 66 theme N-glycosylation 934:948 arg1 level 914:918 expression level 903:918 expression level 903:918 We demonstrated that glycosylation of CDCP1 is a prerequisite for protein stability and plasma membrane localization, and that the expression level and extent of N-glycosylation of CDCP1 correlated with metastatic status. 26497208 5 66 theme N-glycosylation 934:948 arg1 extent 924:929 extent 924:929 extent 924:929 We demonstrated that glycosylation of CDCP1 is a prerequisite for protein stability and plasma membrane localization, and that the expression level and extent of N-glycosylation of CDCP1 correlated with metastatic status. 26497208 8 67 with urine 1430:1434 arg1 disease 1451:1457 high-risk disease 1441:1457 high-risk disease 1441:1457 Employing immunoaffinity mass spectrometry, we detected elevated levels of circulating CDCP1 in patient urine with high-risk disease. 26497208 1 68 theme protein 139:145 arg1 regulator 147:155 a trans-membrane protein regulator 122:155 a trans-membrane protein regulator of cell adhesion with a potent pro-migratory function in tumors 122:219 CUB-domain-containing protein 1 (CDCP1) is a trans-membrane protein regulator of cell adhesion with a potent pro-migratory function in tumors. 26497208 1 68 theme protein 139:145 arg1 protein 101:107 CUB-domain-containing protein 1 79:109 CUB-domain-containing protein 1 (CDCP1) 79:117 CUB-domain-containing protein 1 (CDCP1) is a trans-membrane protein regulator of cell adhesion with a potent pro-migratory function in tumors. 26497208 6 69 theme acid 1046:1049 arg1 chains 1051:1056 sialic acid chains 1039:1056 sialic acid chains 1039:1056 Interestingly, complex N-linked glycans with sialic acid chains were restricted to the N-terminal half of the ectodomain and absent in the truncated species. 26497208 6 70 with glycans 1026:1032 arg1 chains 1051:1056 sialic acid chains 1039:1056 sialic acid chains 1039:1056 Interestingly, complex N-linked glycans with sialic acid chains were restricted to the N-terminal half of the ectodomain and absent in the truncated species. 26497208 8 71 theme circulating 1401:1411 arg1 CDCP1 1413:1417 circulating CDCP1 1401:1417 circulating CDCP1 1401:1417 Employing immunoaffinity mass spectrometry, we detected elevated levels of circulating CDCP1 in patient urine with high-risk disease. 26497208 9 72 gly glycosylation 1500:1512 arg1 CDCP1 1573:1577 CDCP1 1573:1577 CDCP1 1573:1577 Our results establish that differential glycosylation, cell surface presentation and extracellular expression of CDCP1 are hallmarks of PCa progression. 26497208 6 73 theme N-linked 1017:1024 arg1 glycans 1026:1032 complex N-linked glycans 1009:1032 complex N-linked glycans with sialic acid chains 1009:1056 Interestingly, complex N-linked glycans with sialic acid chains were restricted to the N-terminal half of the ectodomain and absent in the truncated species. 26497208 7 74 theme circulating 1227:1237 arg1 forms 1239:1243 novel circulating forms 1221:1243 novel circulating forms 1221:1243 Characterization of the extracellular expression of CDCP1 identified novel circulating forms and revealed that extracellular vesicles provide additional processing pathways. 26497208 6 75 theme ectodomain 1104:1113 arg1 half 1092:1095 the N-terminal half 1077:1095 the N-terminal half of the ectodomain 1077:1113 Interestingly, complex N-linked glycans with sialic acid chains were restricted to the N-terminal half of the ectodomain and absent in the truncated species. 26497208 2 76 theme CDCP1 407:411 arg1 expression 393:402 expression 393:402 expression of CDCP1 in prostate cancer 393:430 Given that proteolytic cleavage of the ectodomain correlates with outside-in oncogenic signaling, we characterized glycosylation in the context of cellular processing and expression of CDCP1 in prostate cancer. 26497208 2 76 theme CDCP1 407:411 arg1 processing 378:387 cellular processing 369:387 cellular processing 369:387 Given that proteolytic cleavage of the ectodomain correlates with outside-in oncogenic signaling, we characterized glycosylation in the context of cellular processing and expression of CDCP1 in prostate cancer. 26497208 5 77 theme CDCP1 953:957 arg1 N-glycosylation 934:948 N-glycosylation 934:948 N-glycosylation of CDCP1 934:957 We demonstrated that glycosylation of CDCP1 is a prerequisite for protein stability and plasma membrane localization, and that the expression level and extent of N-glycosylation of CDCP1 correlated with metastatic status. 26497208 4 78 theme adjacent 738:745 arg1 tissues 763:769 adjacent normal prostate tissues 738:769 adjacent normal prostate tissues 738:769 The relative expression of full-length CDCP1 correlated with the metastatic potential of syngeneic cell models and an increase in surface membrane expression of CDCP1 was observed in tumor compared to adjacent normal prostate tissues. 26497208 2 79 theme expression 393:402 arg1 context 358:364 the context 354:364 the context of cellular processing and expression of CDCP1 in prostate cancer 354:430 Given that proteolytic cleavage of the ectodomain correlates with outside-in oncogenic signaling, we characterized glycosylation in the context of cellular processing and expression of CDCP1 in prostate cancer. 26497208 0 80 theme cell 27:30 arg1 glycoprotein 40:51 cell surface glycoprotein 27:51 cell surface glycoprotein 27:51 Dysregulated expression of cell surface glycoprotein CDCP1 in prostate cancer. 26497208 6 81 theme N-terminal 1081:1090 arg1 half 1092:1095 the N-terminal half 1077:1095 the N-terminal half of the ectodomain 1077:1113 Interestingly, complex N-linked glycans with sialic acid chains were restricted to the N-terminal half of the ectodomain and absent in the truncated species. 26497208 4 82 theme CDCP1 576:580 arg1 expression 550:559 The relative expression 537:559 The relative expression of full-length CDCP1 537:580 The relative expression of full-length CDCP1 correlated with the metastatic potential of syngeneic cell models and an increase in surface membrane expression of CDCP1 was observed in tumor compared to adjacent normal prostate tissues. 26497208 4 83 theme prostate 754:761 arg1 tissues 763:769 adjacent normal prostate tissues 738:769 adjacent normal prostate tissues 738:769 The relative expression of full-length CDCP1 correlated with the metastatic potential of syngeneic cell models and an increase in surface membrane expression of CDCP1 was observed in tumor compared to adjacent normal prostate tissues. 26497208 3 84 theme 70 491:492 arg1 kDa 494:496 kDa 494:496 kDa 494:496 We detected 135 kDa full-length and proteolytic processed 70 kDa species in a panel of PCa cell models. 26497208 7 85 theme extracellular 1176:1188 arg1 expression 1190:1199 the extracellular expression 1172:1199 the extracellular expression of CDCP1 1172:1208 Characterization of the extracellular expression of CDCP1 identified novel circulating forms and revealed that extracellular vesicles provide additional processing pathways. 26497208 6 86 from species 1143:1149 arg1 absent 1119:1124 absent 1119:1124 absent 1119:1124 Interestingly, complex N-linked glycans with sialic acid chains were restricted to the N-terminal half of the ectodomain and absent in the truncated species. 26497208 2 87 theme prostate 416:423 arg1 cancer 425:430 prostate cancer 416:430 prostate cancer 416:430 Given that proteolytic cleavage of the ectodomain correlates with outside-in oncogenic signaling, we characterized glycosylation in the context of cellular processing and expression of CDCP1 in prostate cancer. 26497208 5 88 theme CDCP1 810:814 arg1 prerequisite 821:832 a prerequisite 819:832 a prerequisite for protein stability and plasma membrane localization 819:887 We demonstrated that glycosylation of CDCP1 is a prerequisite for protein stability and plasma membrane localization, and that the expression level and extent of N-glycosylation of CDCP1 correlated with metastatic status. 26497208 5 88 theme CDCP1 810:814 arg1 glycosylation 793:805 glycosylation 793:805 glycosylation of CDCP1 793:814 We demonstrated that glycosylation of CDCP1 is a prerequisite for protein stability and plasma membrane localization, and that the expression level and extent of N-glycosylation of CDCP1 correlated with metastatic status. 26497208 2 89 from expression 393:402 arg1 cancer 425:430 prostate cancer 416:430 prostate cancer 416:430 Given that proteolytic cleavage of the ectodomain correlates with outside-in oncogenic signaling, we characterized glycosylation in the context of cellular processing and expression of CDCP1 in prostate cancer. 26497208 4 90 theme relative 541:548 arg1 expression 550:559 The relative expression 537:559 The relative expression of full-length CDCP1 537:580 The relative expression of full-length CDCP1 correlated with the metastatic potential of syngeneic cell models and an increase in surface membrane expression of CDCP1 was observed in tumor compared to adjacent normal prostate tissues. 26497208 5 91 gly glycosylation 793:805 arg1 CDCP1 810:814 CDCP1 810:814 CDCP1 810:814 We demonstrated that glycosylation of CDCP1 is a prerequisite for protein stability and plasma membrane localization, and that the expression level and extent of N-glycosylation of CDCP1 correlated with metastatic status. 26497208 6 92 from absent 1119:1124 arg1 species 1143:1149 the truncated species 1129:1149 the truncated species 1129:1149 Interestingly, complex N-linked glycans with sialic acid chains were restricted to the N-terminal half of the ectodomain and absent in the truncated species. 26497208 2 93 theme processing 378:387 arg1 context 358:364 the context 354:364 the context of cellular processing and expression of CDCP1 in prostate cancer 354:430 Given that proteolytic cleavage of the ectodomain correlates with outside-in oncogenic signaling, we characterized glycosylation in the context of cellular processing and expression of CDCP1 in prostate cancer. 26497208 3 94 dep processed 481:489 arg1 kDa 449:451 135 kDa 445:451 135 kDa full-length and proteolytic 445:479 We detected 135 kDa full-length and proteolytic processed 70 kDa species in a panel of PCa cell models. 26497208 3 95 theme full-length 453:463 arg1 kDa 449:451 135 kDa 445:451 135 kDa full-length and proteolytic 445:479 We detected 135 kDa full-length and proteolytic processed 70 kDa species in a panel of PCa cell models. 26497208 4 96 theme cell 636:639 arg1 models 641:646 syngeneic cell models 626:646 syngeneic cell models 626:646 The relative expression of full-length CDCP1 correlated with the metastatic potential of syngeneic cell models and an increase in surface membrane expression of CDCP1 was observed in tumor compared to adjacent normal prostate tissues. 26497208 3 97 theme cell 524:527 arg1 models 529:534 PCa cell models 520:534 PCa cell models 520:534 We detected 135 kDa full-length and proteolytic processed 70 kDa species in a panel of PCa cell models. 26497208 9 98 theme differential 1487:1498 arg1 presentation 1528:1539 cell surface presentation 1515:1539 cell surface presentation 1515:1539 Our results establish that differential glycosylation, cell surface presentation and extracellular expression of CDCP1 are hallmarks of PCa progression. 26497208 9 98 theme differential 1487:1498 arg1 expression 1559:1568 extracellular expression 1545:1568 extracellular expression of CDCP1 1545:1577 Our results establish that differential glycosylation, cell surface presentation and extracellular expression of CDCP1 are hallmarks of PCa progression. 26497208 9 98 theme differential 1487:1498 arg1 glycosylation 1500:1512 differential glycosylation 1487:1512 differential glycosylation 1487:1512 Our results establish that differential glycosylation, cell surface presentation and extracellular expression of CDCP1 are hallmarks of PCa progression. 26497208 9 98 theme differential 1487:1498 arg1 hallmarks 1583:1591 hallmarks 1583:1591 hallmarks of PCa progression 1583:1610 Our results establish that differential glycosylation, cell surface presentation and extracellular expression of CDCP1 are hallmarks of PCa progression. 25615530 5 0 gly glycosylation 757:769 arg1 apparatus 814:822 the Golgi apparatus 804:822 the Golgi apparatus 804:822 In this study, we show that TREM2 with NHD mutations are impaired in the glycosylation with complex oligosaccharides in the Golgi apparatus, in the trafficking to plasma membrane and further processing by γ-secretase. 25615530 5 1 from glycosylation 757:769 arg1 apparatus 814:822 the Golgi apparatus 804:822 the Golgi apparatus 804:822 In this study, we show that TREM2 with NHD mutations are impaired in the glycosylation with complex oligosaccharides in the Golgi apparatus, in the trafficking to plasma membrane and further processing by γ-secretase. 25615530 2 2 theme early 340:344 arg1 onset 346:350 early onset 340:350 early onset of dementia and bone cysts 340:377 Mutations of Q33X, Y38C and T66M cause Nasu-Hakola disease (NHD) which is characterized by early onset of dementia and bone cysts. 25615530 6 3 theme R47H 911:914 arg1 mutation 916:923 R47H mutation 911:923 R47H mutation in AD 911:929 Although R47H mutation in AD affected the glycosylation and normal trafficking of TREM2 less, the detailed pattern of glycosylated TREM2 differs from that of the wild type, thus suggesting that precise regulation of TREM2 glycosylation is impaired when arginine at 47 is mutated to histidine. 25615530 6 4 theme normal 962:967 arg1 trafficking 969:979 normal trafficking 962:979 normal trafficking 962:979 Although R47H mutation in AD affected the glycosylation and normal trafficking of TREM2 less, the detailed pattern of glycosylated TREM2 differs from that of the wild type, thus suggesting that precise regulation of TREM2 glycosylation is impaired when arginine at 47 is mutated to histidine. 25615530 7 5 theme plasma 1377:1382 arg1 membrane 1384:1391 the plasma membrane 1373:1391 the plasma membrane 1373:1391 Our results suggest that the impaired glycosylation and trafficking of TREM2 from endoplasmic reticulum/Golgi to plasma membrane by mutations may inhibit its normal functions in the plasma membrane, which may contribute to the disease. 25615530 6 6 from mutation 916:923 arg1 AD 928:929 AD 928:929 AD 928:929 Although R47H mutation in AD affected the glycosylation and normal trafficking of TREM2 less, the detailed pattern of glycosylated TREM2 differs from that of the wild type, thus suggesting that precise regulation of TREM2 glycosylation is impaired when arginine at 47 is mutated to histidine. 25615530 4 7 dep known 677:681 arg1 affect 588:593 affect 588:593 affect the trafficking of TREM2, which may affect the normal functions of TREM2 588:666 However, how these mutations affect the trafficking of TREM2, which may affect the normal functions of TREM2, was not known. 25615530 6 8 theme precise 1096:1102 arg1 regulation 1104:1113 precise regulation 1096:1113 precise regulation of TREM2 glycosylation 1096:1136 Although R47H mutation in AD affected the glycosylation and normal trafficking of TREM2 less, the detailed pattern of glycosylated TREM2 differs from that of the wild type, thus suggesting that precise regulation of TREM2 glycosylation is impaired when arginine at 47 is mutated to histidine. 25615530 7 9 theme TREM2 1266:1270 arg1 trafficking 1251:1261 trafficking 1251:1261 trafficking 1251:1261 Our results suggest that the impaired glycosylation and trafficking of TREM2 from endoplasmic reticulum/Golgi to plasma membrane by mutations may inhibit its normal functions in the plasma membrane, which may contribute to the disease. 25615530 7 9 theme TREM2 1266:1270 arg1 glycosylation 1233:1245 impaired glycosylation 1224:1245 impaired glycosylation 1224:1245 Our results suggest that the impaired glycosylation and trafficking of TREM2 from endoplasmic reticulum/Golgi to plasma membrane by mutations may inhibit its normal functions in the plasma membrane, which may contribute to the disease. 25615530 6 10 theme wild 1064:1067 arg1 type 1069:1072 the wild type 1060:1072 the wild type 1060:1072 Although R47H mutation in AD affected the glycosylation and normal trafficking of TREM2 less, the detailed pattern of glycosylated TREM2 differs from that of the wild type, thus suggesting that precise regulation of TREM2 glycosylation is impaired when arginine at 47 is mutated to histidine. 25615530 6 11 dep glycosylation 944:956 arg1 the 940:942 the 940:942 the 940:942 Although R47H mutation in AD affected the glycosylation and normal trafficking of TREM2 less, the detailed pattern of glycosylated TREM2 differs from that of the wild type, thus suggesting that precise regulation of TREM2 glycosylation is impaired when arginine at 47 is mutated to histidine. 25615530 2 12 theme Nasu-Hakola 288:298 arg1 disease 300:306 Nasu-Hakola disease 288:306 Nasu-Hakola disease (NHD) which is characterized by early onset of dementia and bone cysts 288:377 Mutations of Q33X, Y38C and T66M cause Nasu-Hakola disease (NHD) which is characterized by early onset of dementia and bone cysts. 25615530 2 12 theme Nasu-Hakola 288:298 arg1 NHD 309:311 NHD 309:311 NHD 309:311 Mutations of Q33X, Y38C and T66M cause Nasu-Hakola disease (NHD) which is characterized by early onset of dementia and bone cysts. 25615530 0 13 theme Golgi 95:99 arg1 Apparatus 101:109 the Golgi Apparatus 91:109 the Golgi Apparatus 91:109 Disease-Associated Mutations of TREM2 Alter the Processing of N-Linked Oligosaccharides in the Golgi Apparatus. 25615530 7 14 from reticulum/Golgi 1289:1303 arg1 trafficking 1251:1261 trafficking 1251:1261 trafficking 1251:1261 Our results suggest that the impaired glycosylation and trafficking of TREM2 from endoplasmic reticulum/Golgi to plasma membrane by mutations may inhibit its normal functions in the plasma membrane, which may contribute to the disease. 25615530 7 14 from reticulum/Golgi 1289:1303 arg1 glycosylation 1233:1245 impaired glycosylation 1224:1245 impaired glycosylation 1224:1245 Our results suggest that the impaired glycosylation and trafficking of TREM2 from endoplasmic reticulum/Golgi to plasma membrane by mutations may inhibit its normal functions in the plasma membrane, which may contribute to the disease. 25615530 5 15 theme further 867:873 arg1 processing 875:884 further processing 867:884 further processing by γ-secretase 867:899 In this study, we show that TREM2 with NHD mutations are impaired in the glycosylation with complex oligosaccharides in the Golgi apparatus, in the trafficking to plasma membrane and further processing by γ-secretase. 25615530 2 16 theme T66M 277:280 arg1 Mutations 249:257 Mutations 249:257 Mutations of Q33X, Y38C and T66M 249:280 Mutations of Q33X, Y38C and T66M cause Nasu-Hakola disease (NHD) which is characterized by early onset of dementia and bone cysts. 25615530 1 17 theme triggering 116:125 arg1 receptor 197:204 an immune-modulatory receptor 176:204 an immune-modulatory receptor involved in phagocytosis and inflammation 176:246 The triggering receptor expressed on myeloid cells 2 (TREM2) is an immune-modulatory receptor involved in phagocytosis and inflammation. 25615530 1 17 theme triggering 116:125 arg1 receptor 127:134 The triggering receptor 112:134 The triggering receptor expressed on myeloid cells 2 (TREM2) 112:171 The triggering receptor expressed on myeloid cells 2 (TREM2) is an immune-modulatory receptor involved in phagocytosis and inflammation. 25615530 4 18 theme TREM2 614:618 arg1 trafficking 599:609 the trafficking 595:609 the trafficking 595:609 However, how these mutations affect the trafficking of TREM2, which may affect the normal functions of TREM2, was not known. 25615530 2 19 theme cysts 373:377 arg1 onset 346:350 early onset 340:350 early onset of dementia and bone cysts 340:377 Mutations of Q33X, Y38C and T66M cause Nasu-Hakola disease (NHD) which is characterized by early onset of dementia and bone cysts. 25615530 5 20 theme Golgi 808:812 arg1 apparatus 814:822 the Golgi apparatus 804:822 the Golgi apparatus 804:822 In this study, we show that TREM2 with NHD mutations are impaired in the glycosylation with complex oligosaccharides in the Golgi apparatus, in the trafficking to plasma membrane and further processing by γ-secretase. 25615530 2 21 theme Y38C 268:271 arg1 Mutations 249:257 Mutations 249:257 Mutations of Q33X, Y38C and T66M 249:280 Mutations of Q33X, Y38C and T66M cause Nasu-Hakola disease (NHD) which is characterized by early onset of dementia and bone cysts. 25615530 2 22 theme bone 368:371 arg1 cysts 373:377 bone cysts 368:377 bone cysts 368:377 Mutations of Q33X, Y38C and T66M cause Nasu-Hakola disease (NHD) which is characterized by early onset of dementia and bone cysts. 25615530 3 23 dep such 480:483 arg1 as 485:486 as 485:486 as 485:486 A recent, genome-wide association study also revealed that single nucleotide polymorphism of TREM2, such as R47H, increased the risk of Alzheimer's disease (AD) similar to ApoE4. 25615530 0 24 from Processing 48:57 arg1 Apparatus 101:109 the Golgi Apparatus 91:109 the Golgi Apparatus 91:109 Disease-Associated Mutations of TREM2 Alter the Processing of N-Linked Oligosaccharides in the Golgi Apparatus. 25615530 3 25 theme genome-wide 390:400 arg1 study 414:418 A recent, genome-wide association study 380:418 study 414:418 A recent, genome-wide association study also revealed that single nucleotide polymorphism of TREM2, such as R47H, increased the risk of Alzheimer's disease (AD) similar to ApoE4. 25615530 0 26 theme Disease-Associated 0:17 arg1 Mutations 19:27 Disease-Associated Mutations 0:27 Disease-Associated Mutations of TREM2 0:36 Disease-Associated Mutations of TREM2 Alter the Processing of N-Linked Oligosaccharides in the Golgi Apparatus. 25615530 6 27 gly glycosylated 1020:1031 arg1 TREM2 1033:1037 glycosylated TREM2 1020:1037 glycosylated TREM2 1020:1037 Although R47H mutation in AD affected the glycosylation and normal trafficking of TREM2 less, the detailed pattern of glycosylated TREM2 differs from that of the wild type, thus suggesting that precise regulation of TREM2 glycosylation is impaired when arginine at 47 is mutated to histidine. 25615530 4 28 theme TREM2 662:666 arg1 functions 649:657 the normal functions 638:657 the normal functions of TREM2 638:666 However, how these mutations affect the trafficking of TREM2, which may affect the normal functions of TREM2, was not known. 25615530 2 29 theme dementia 355:362 arg1 onset 346:350 early onset 340:350 early onset of dementia and bone cysts 340:377 Mutations of Q33X, Y38C and T66M cause Nasu-Hakola disease (NHD) which is characterized by early onset of dementia and bone cysts. 25615530 0 30 theme TREM2 32:36 arg1 Mutations 19:27 Disease-Associated Mutations 0:27 Disease-Associated Mutations of TREM2 0:36 Disease-Associated Mutations of TREM2 Alter the Processing of N-Linked Oligosaccharides in the Golgi Apparatus. 25615530 5 31 with TREM2 712:716 arg1 mutations 727:735 NHD mutations 723:735 NHD mutations 723:735 In this study, we show that TREM2 with NHD mutations are impaired in the glycosylation with complex oligosaccharides in the Golgi apparatus, in the trafficking to plasma membrane and further processing by γ-secretase. 25615530 5 32 theme plasma 847:852 arg1 membrane 854:861 plasma membrane 847:861 plasma membrane 847:861 In this study, we show that TREM2 with NHD mutations are impaired in the glycosylation with complex oligosaccharides in the Golgi apparatus, in the trafficking to plasma membrane and further processing by γ-secretase. 25615530 7 33 theme endoplasmic 1277:1287 arg1 reticulum/Golgi 1289:1303 endoplasmic reticulum/Golgi 1277:1303 endoplasmic reticulum/Golgi to plasma membrane by mutations 1277:1335 Our results suggest that the impaired glycosylation and trafficking of TREM2 from endoplasmic reticulum/Golgi to plasma membrane by mutations may inhibit its normal functions in the plasma membrane, which may contribute to the disease. 25615530 1 34 theme immune-modulatory 179:195 arg1 receptor 197:204 an immune-modulatory receptor 176:204 an immune-modulatory receptor involved in phagocytosis and inflammation 176:246 The triggering receptor expressed on myeloid cells 2 (TREM2) is an immune-modulatory receptor involved in phagocytosis and inflammation. 25615530 1 34 theme immune-modulatory 179:195 arg1 receptor 127:134 The triggering receptor 112:134 The triggering receptor expressed on myeloid cells 2 (TREM2) 112:171 The triggering receptor expressed on myeloid cells 2 (TREM2) is an immune-modulatory receptor involved in phagocytosis and inflammation. 25615530 5 35 theme NHD 723:725 arg1 mutations 727:735 NHD mutations 723:735 NHD mutations 723:735 In this study, we show that TREM2 with NHD mutations are impaired in the glycosylation with complex oligosaccharides in the Golgi apparatus, in the trafficking to plasma membrane and further processing by γ-secretase. 25615530 1 36 dep cells 157:161 arg1 TREM2 166:170 TREM2 166:170 TREM2 166:170 The triggering receptor expressed on myeloid cells 2 (TREM2) is an immune-modulatory receptor involved in phagocytosis and inflammation. 25615530 1 36 dep cells 157:161 arg1 2 163:163 2 163:163 2 163:163 The triggering receptor expressed on myeloid cells 2 (TREM2) is an immune-modulatory receptor involved in phagocytosis and inflammation. 25615530 3 37 theme nucleotide 446:455 arg1 polymorphism 457:468 single nucleotide polymorphism 439:468 single nucleotide polymorphism of TREM2, such as R47H, 439:492 A recent, genome-wide association study also revealed that single nucleotide polymorphism of TREM2, such as R47H, increased the risk of Alzheimer's disease (AD) similar to ApoE4. 25615530 3 38 theme recent 382:387 arg1 study 414:418 A recent, genome-wide association study 380:418 study 414:418 A recent, genome-wide association study also revealed that single nucleotide polymorphism of TREM2, such as R47H, increased the risk of Alzheimer's disease (AD) similar to ApoE4. 25615530 3 39 theme similar 541:547 arg1 risk 508:511 the risk 504:511 the risk of Alzheimer's disease (AD) similar to ApoE4 504:556 A recent, genome-wide association study also revealed that single nucleotide polymorphism of TREM2, such as R47H, increased the risk of Alzheimer's disease (AD) similar to ApoE4. 25615530 3 40 theme association 402:412 arg1 study 414:418 A recent, genome-wide association study 380:418 study 414:418 A recent, genome-wide association study also revealed that single nucleotide polymorphism of TREM2, such as R47H, increased the risk of Alzheimer's disease (AD) similar to ApoE4. 25615530 6 41 gly glycosylation 944:956 arg1 TREM2 984:988 TREM2 984:988 TREM2 984:988 Although R47H mutation in AD affected the glycosylation and normal trafficking of TREM2 less, the detailed pattern of glycosylated TREM2 differs from that of the wild type, thus suggesting that precise regulation of TREM2 glycosylation is impaired when arginine at 47 is mutated to histidine. 25615530 6 42 theme glycosylation 1124:1136 arg1 regulation 1104:1113 precise regulation 1096:1113 precise regulation of TREM2 glycosylation 1096:1136 Although R47H mutation in AD affected the glycosylation and normal trafficking of TREM2 less, the detailed pattern of glycosylated TREM2 differs from that of the wild type, thus suggesting that precise regulation of TREM2 glycosylation is impaired when arginine at 47 is mutated to histidine. 25615530 7 43 dep glycosylation 1233:1245 arg1 the 1220:1222 the 1220:1222 the 1220:1222 Our results suggest that the impaired glycosylation and trafficking of TREM2 from endoplasmic reticulum/Golgi to plasma membrane by mutations may inhibit its normal functions in the plasma membrane, which may contribute to the disease. 25615530 6 44 theme TREM2 1118:1122 arg1 glycosylation 1124:1136 TREM2 glycosylation 1118:1136 TREM2 glycosylation 1118:1136 Although R47H mutation in AD affected the glycosylation and normal trafficking of TREM2 less, the detailed pattern of glycosylated TREM2 differs from that of the wild type, thus suggesting that precise regulation of TREM2 glycosylation is impaired when arginine at 47 is mutated to histidine. 25615530 7 45 theme normal 1353:1358 arg1 functions 1360:1368 its normal functions 1349:1368 its normal functions 1349:1368 Our results suggest that the impaired glycosylation and trafficking of TREM2 from endoplasmic reticulum/Golgi to plasma membrane by mutations may inhibit its normal functions in the plasma membrane, which may contribute to the disease. 25615530 3 46 theme TREM2 473:477 arg1 polymorphism 457:468 single nucleotide polymorphism 439:468 single nucleotide polymorphism of TREM2, such as R47H, 439:492 A recent, genome-wide association study also revealed that single nucleotide polymorphism of TREM2, such as R47H, increased the risk of Alzheimer's disease (AD) similar to ApoE4. 25615530 7 47 theme impaired 1224:1231 arg1 glycosylation 1233:1245 impaired glycosylation 1224:1245 impaired glycosylation 1224:1245 Our results suggest that the impaired glycosylation and trafficking of TREM2 from endoplasmic reticulum/Golgi to plasma membrane by mutations may inhibit its normal functions in the plasma membrane, which may contribute to the disease. 25615530 6 48 theme TREM2 1033:1037 arg1 pattern 1009:1015 the detailed pattern 996:1015 the detailed pattern of glycosylated TREM2 996:1037 Although R47H mutation in AD affected the glycosylation and normal trafficking of TREM2 less, the detailed pattern of glycosylated TREM2 differs from that of the wild type, thus suggesting that precise regulation of TREM2 glycosylation is impaired when arginine at 47 is mutated to histidine. 25615530 4 49 theme normal 642:647 arg1 functions 649:657 the normal functions 638:657 the normal functions of TREM2 638:666 However, how these mutations affect the trafficking of TREM2, which may affect the normal functions of TREM2, was not known. 25615530 1 50 theme myeloid 149:155 arg1 cells 157:161 myeloid cells 2 (TREM2) 149:171 myeloid cells 2 (TREM2) 149:171 The triggering receptor expressed on myeloid cells 2 (TREM2) is an immune-modulatory receptor involved in phagocytosis and inflammation. 25615530 6 51 theme glycosylated 1020:1031 arg1 TREM2 1033:1037 glycosylated TREM2 1020:1037 glycosylated TREM2 1020:1037 Although R47H mutation in AD affected the glycosylation and normal trafficking of TREM2 less, the detailed pattern of glycosylated TREM2 differs from that of the wild type, thus suggesting that precise regulation of TREM2 glycosylation is impaired when arginine at 47 is mutated to histidine. 25615530 5 52 theme complex 776:782 arg1 oligosaccharides 784:799 complex oligosaccharides 776:799 complex oligosaccharides 776:799 In this study, we show that TREM2 with NHD mutations are impaired in the glycosylation with complex oligosaccharides in the Golgi apparatus, in the trafficking to plasma membrane and further processing by γ-secretase. 25615530 7 53 theme plasma 1308:1313 arg1 membrane 1315:1322 plasma membrane 1308:1322 plasma membrane 1308:1322 Our results suggest that the impaired glycosylation and trafficking of TREM2 from endoplasmic reticulum/Golgi to plasma membrane by mutations may inhibit its normal functions in the plasma membrane, which may contribute to the disease. 25615530 5 54 with glycosylation 757:769 arg1 oligosaccharides 784:799 complex oligosaccharides 776:799 complex oligosaccharides 776:799 In this study, we show that TREM2 with NHD mutations are impaired in the glycosylation with complex oligosaccharides in the Golgi apparatus, in the trafficking to plasma membrane and further processing by γ-secretase. 25615530 2 55 theme Q33X 262:265 arg1 Mutations 249:257 Mutations 249:257 Mutations of Q33X, Y38C and T66M 249:280 Mutations of Q33X, Y38C and T66M cause Nasu-Hakola disease (NHD) which is characterized by early onset of dementia and bone cysts. 25615530 6 56 from 47 1167:1168 arg1 arginine 1155:1162 arginine 1155:1162 arginine at 47 1155:1168 Although R47H mutation in AD affected the glycosylation and normal trafficking of TREM2 less, the detailed pattern of glycosylated TREM2 differs from that of the wild type, thus suggesting that precise regulation of TREM2 glycosylation is impaired when arginine at 47 is mutated to histidine. 25615530 0 57 theme Oligosaccharides 71:86 arg1 Processing 48:57 the Processing 44:57 the Processing of N-Linked Oligosaccharides in the Golgi Apparatus 44:109 Disease-Associated Mutations of TREM2 Alter the Processing of N-Linked Oligosaccharides in the Golgi Apparatus. 25615530 3 58 theme single 439:444 arg1 polymorphism 457:468 single nucleotide polymorphism 439:468 single nucleotide polymorphism of TREM2, such as R47H, 439:492 A recent, genome-wide association study also revealed that single nucleotide polymorphism of TREM2, such as R47H, increased the risk of Alzheimer's disease (AD) similar to ApoE4. 25615530 3 59 theme R47H 488:491 arg1 polymorphism 457:468 single nucleotide polymorphism 439:468 single nucleotide polymorphism of TREM2, such as R47H, 439:492 A recent, genome-wide association study also revealed that single nucleotide polymorphism of TREM2, such as R47H, increased the risk of Alzheimer's disease (AD) similar to ApoE4. 25615530 6 60 theme TREM2 984:988 arg1 glycosylation 944:956 glycosylation 944:956 glycosylation 944:956 Although R47H mutation in AD affected the glycosylation and normal trafficking of TREM2 less, the detailed pattern of glycosylated TREM2 differs from that of the wild type, thus suggesting that precise regulation of TREM2 glycosylation is impaired when arginine at 47 is mutated to histidine. 25615530 6 60 theme TREM2 984:988 arg1 trafficking 969:979 normal trafficking 962:979 normal trafficking 962:979 Although R47H mutation in AD affected the glycosylation and normal trafficking of TREM2 less, the detailed pattern of glycosylated TREM2 differs from that of the wild type, thus suggesting that precise regulation of TREM2 glycosylation is impaired when arginine at 47 is mutated to histidine. 25615530 0 61 theme N-Linked 62:69 arg1 Oligosaccharides 71:86 N-Linked Oligosaccharides 62:86 N-Linked Oligosaccharides 62:86 Disease-Associated Mutations of TREM2 Alter the Processing of N-Linked Oligosaccharides in the Golgi Apparatus. 25615530 7 62 gly glycosylation 1233:1245 arg1 TREM2 1266:1270 TREM2 1266:1270 TREM2 1266:1270 Our results suggest that the impaired glycosylation and trafficking of TREM2 from endoplasmic reticulum/Golgi to plasma membrane by mutations may inhibit its normal functions in the plasma membrane, which may contribute to the disease. 25615530 6 63 theme detailed 1000:1007 arg1 pattern 1009:1015 the detailed pattern 996:1015 the detailed pattern of glycosylated TREM2 996:1037 Although R47H mutation in AD affected the glycosylation and normal trafficking of TREM2 less, the detailed pattern of glycosylated TREM2 differs from that of the wild type, thus suggesting that precise regulation of TREM2 glycosylation is impaired when arginine at 47 is mutated to histidine. 25339106 7 0 theme positional 1082:1091 arg1 A 1113:1113 A 1113:1113 A 1113:1113 Assays using fluoresceinated glycans showed that 3-O-sulfated Le(X) (suLe(X)) bound to receptors localized on the head of nearly 60% of uncapacitated boar sperm but that the positional isomer 3-O-sulfo-Le(A) (suLe(A)) bound to <5% of sperm. 25339106 7 0 theme positional 1082:1091 arg1 3-O-sulfo-Le 1100:1111 the positional isomer 3-O-sulfo-Le 1078:1111 the positional isomer 3-O-sulfo-Le(A) (suLe(A)) 1078:1124 Assays using fluoresceinated glycans showed that 3-O-sulfated Le(X) (suLe(X)) bound to receptors localized on the head of nearly 60% of uncapacitated boar sperm but that the positional isomer 3-O-sulfo-Le(A) (suLe(A)) bound to <5% of sperm. 25339106 2 1 theme molecular 320:328 arg1 unclear 386:392 unclear 386:392 unclear 386:392 The precise molecular interactions that allow formation of this reservoir are unclear. 25339106 2 1 theme molecular 320:328 arg1 interactions 330:341 The precise molecular interactions 308:341 The precise molecular interactions that allow formation of this reservoir 308:380 The precise molecular interactions that allow formation of this reservoir are unclear. 25339106 4 2 theme Lewis 544:548 arg1 trisaccharides 550:563 Lewis trisaccharides 544:563 Lewis trisaccharides 544:563 Previous results indicated that Lewis trisaccharides are present in glycosphingolipids and O- and N-linked glycans of the porcine isthmus and that Le(X)-containing molecules bind porcine sperm. 25339106 4 3 from present 569:575 arg1 O- 603:604 O- 603:604 O- 603:604 Previous results indicated that Lewis trisaccharides are present in glycosphingolipids and O- and N-linked glycans of the porcine isthmus and that Le(X)-containing molecules bind porcine sperm. 25339106 4 3 from present 569:575 arg1 glycosphingolipids 580:597 glycosphingolipids 580:597 glycosphingolipids 580:597 Previous results indicated that Lewis trisaccharides are present in glycosphingolipids and O- and N-linked glycans of the porcine isthmus and that Le(X)-containing molecules bind porcine sperm. 25339106 0 4 from glycans 18:24 arg1 epithelium 51:60 the porcine oviductal epithelium 29:60 the porcine oviductal epithelium 29:60 LewisX-containing glycans on the porcine oviductal epithelium contribute to formation of the sperm reservoir. 25339106 3 5 theme oviductal 461:469 arg1 ligands 476:482 their oviductal cell ligands 455:482 their oviductal cell ligands 455:482 It is proposed that binding of sperm receptors (lectins) to their oviductal cell ligands is accomplished by glycans. 25339106 0 6 theme reservoir 99:107 arg1 formation 76:84 formation 76:84 formation of the sperm reservoir 76:107 LewisX-containing glycans on the porcine oviductal epithelium contribute to formation of the sperm reservoir. 25339106 5 7 from trisaccharides 826:839 arg1 fact 804:807 fact 804:807 fact 804:807 Immunohistochemistry indicated that the Lewis structures identified by mass spectrometry were, in fact, Lewis X (Le(X)) trisaccharides. 25339106 12 8 theme -related 1683:1690 arg1 moieties 1692:1699 Le(X)-related moieties 1678:1699 Le(X)-related moieties 1678:1699 These results demonstrate that the oviduct isthmus contains Le(X)-related moieties and that sperm binding to these oviduct glycans is necessary and sufficient for forming the sperm reservoir. 25339106 0 9 theme sperm 93:97 arg1 reservoir 99:107 the sperm reservoir 89:107 the sperm reservoir 89:107 LewisX-containing glycans on the porcine oviductal epithelium contribute to formation of the sperm reservoir. 25339106 7 10 theme localized 1005:1013 arg1 receptors 995:1003 receptors 995:1003 receptors localized on the head of nearly 60% of uncapacitated boar sperm 995:1067 Assays using fluoresceinated glycans showed that 3-O-sulfated Le(X) (suLe(X)) bound to receptors localized on the head of nearly 60% of uncapacitated boar sperm but that the positional isomer 3-O-sulfo-Le(A) (suLe(A)) bound to <5% of sperm. 25339106 10 11 theme isthmic 1459:1465 arg1 aggregates 1467:1476 isthmic aggregates 1459:1476 isthmic aggregates 1459:1476 Pretreatment of oviduct cell aggregates with the Le(X) antibody blocked 57% of sperm binding to isthmic aggregates. 25339106 7 12 theme sperm 1063:1067 arg1 sperm 1063:1067 uncapacitated boar sperm 1044:1067 uncapacitated boar sperm 1044:1067 Assays using fluoresceinated glycans showed that 3-O-sulfated Le(X) (suLe(X)) bound to receptors localized on the head of nearly 60% of uncapacitated boar sperm but that the positional isomer 3-O-sulfo-Le(A) (suLe(A)) bound to <5% of sperm. 25339106 7 12 theme sperm 1063:1067 arg1 % 1039:1039 nearly 60% 1030:1039 nearly 60% of uncapacitated boar sperm 1030:1067 Assays using fluoresceinated glycans showed that 3-O-sulfated Le(X) (suLe(X)) bound to receptors localized on the head of nearly 60% of uncapacitated boar sperm but that the positional isomer 3-O-sulfo-Le(A) (suLe(A)) bound to <5% of sperm. 25339106 3 13 theme receptors 432:440 arg1 binding 415:421 binding 415:421 binding of sperm receptors (lectins) to their oviductal cell ligands 415:482 It is proposed that binding of sperm receptors (lectins) to their oviductal cell ligands is accomplished by glycans. 25339106 10 14 theme Le 1412:1413 arg1 antibody 1418:1425 the Le(X) antibody 1408:1425 the Le(X) antibody 1408:1425 Pretreatment of oviduct cell aggregates with the Le(X) antibody blocked 57% of sperm binding to isthmic aggregates. 25339106 5 15 theme X 816:816 arg1 trisaccharides 826:839 Lewis X (Le(X)) trisaccharides 810:839 Lewis X (Le(X)) trisaccharides 810:839 Immunohistochemistry indicated that the Lewis structures identified by mass spectrometry were, in fact, Lewis X (Le(X)) trisaccharides. 25339106 5 15 theme X 816:816 arg1 structures 752:761 the Lewis structures 742:761 the Lewis structures identified by mass spectrometry 742:793 Immunohistochemistry indicated that the Lewis structures identified by mass spectrometry were, in fact, Lewis X (Le(X)) trisaccharides. 25339106 9 16 theme suLe 1265:1268 arg1 ability 1254:1260 the ability 1250:1260 the ability of suLe(X) to bind sperm to <10%, perhaps helping to explain why sperm are released at capacitation 1250:1360 Capacitation reduced the ability of suLe(X) to bind sperm to <10%, perhaps helping to explain why sperm are released at capacitation. 25339106 5 17 theme Lewis 746:750 arg1 trisaccharides 826:839 Lewis X (Le(X)) trisaccharides 810:839 Lewis X (Le(X)) trisaccharides 810:839 Immunohistochemistry indicated that the Lewis structures identified by mass spectrometry were, in fact, Lewis X (Le(X)) trisaccharides. 25339106 5 17 theme Lewis 746:750 arg1 structures 752:761 the Lewis structures 742:761 the Lewis structures identified by mass spectrometry 742:793 Immunohistochemistry indicated that the Lewis structures identified by mass spectrometry were, in fact, Lewis X (Le(X)) trisaccharides. 25339106 7 18 theme boar 1058:1061 arg1 sperm 1063:1067 uncapacitated boar sperm 1044:1067 uncapacitated boar sperm 1044:1067 Assays using fluoresceinated glycans showed that 3-O-sulfated Le(X) (suLe(X)) bound to receptors localized on the head of nearly 60% of uncapacitated boar sperm but that the positional isomer 3-O-sulfo-Le(A) (suLe(A)) bound to <5% of sperm. 25339106 5 19 theme mass 777:780 arg1 spectrometry 782:793 mass spectrometry 777:793 mass spectrometry 777:793 Immunohistochemistry indicated that the Lewis structures identified by mass spectrometry were, in fact, Lewis X (Le(X)) trisaccharides. 25339106 7 20 theme isomer 1093:1098 arg1 A 1113:1113 A 1113:1113 A 1113:1113 Assays using fluoresceinated glycans showed that 3-O-sulfated Le(X) (suLe(X)) bound to receptors localized on the head of nearly 60% of uncapacitated boar sperm but that the positional isomer 3-O-sulfo-Le(A) (suLe(A)) bound to <5% of sperm. 25339106 7 20 theme isomer 1093:1098 arg1 3-O-sulfo-Le 1100:1111 the positional isomer 3-O-sulfo-Le 1078:1111 the positional isomer 3-O-sulfo-Le(A) (suLe(A)) 1078:1124 Assays using fluoresceinated glycans showed that 3-O-sulfated Le(X) (suLe(X)) bound to receptors localized on the head of nearly 60% of uncapacitated boar sperm but that the positional isomer 3-O-sulfo-Le(A) (suLe(A)) bound to <5% of sperm. 25339106 12 21 theme oviduct 1733:1739 arg1 glycans 1741:1747 these oviduct glycans 1727:1747 these oviduct glycans 1727:1747 These results demonstrate that the oviduct isthmus contains Le(X)-related moieties and that sperm binding to these oviduct glycans is necessary and sufficient for forming the sperm reservoir. 25339106 6 22 theme isthmus 899:905 arg1 border 885:890 the luminal border 873:890 the luminal border of the isthmus 873:905 These motifs were localized to the luminal border of the isthmus. 25339106 4 23 theme porcine 691:697 arg1 sperm 699:703 porcine sperm 691:703 porcine sperm 691:703 Previous results indicated that Lewis trisaccharides are present in glycosphingolipids and O- and N-linked glycans of the porcine isthmus and that Le(X)-containing molecules bind porcine sperm. 25339106 4 24 theme isthmus 642:648 arg1 O- 603:604 O- 603:604 O- 603:604 Previous results indicated that Lewis trisaccharides are present in glycosphingolipids and O- and N-linked glycans of the porcine isthmus and that Le(X)-containing molecules bind porcine sperm. 25339106 4 24 theme isthmus 642:648 arg1 glycans 619:625 N-linked glycans 610:625 N-linked glycans 610:625 Previous results indicated that Lewis trisaccharides are present in glycosphingolipids and O- and N-linked glycans of the porcine isthmus and that Le(X)-containing molecules bind porcine sperm. 25339106 4 24 theme isthmus 642:648 arg1 glycosphingolipids 580:597 glycosphingolipids 580:597 glycosphingolipids 580:597 Previous results indicated that Lewis trisaccharides are present in glycosphingolipids and O- and N-linked glycans of the porcine isthmus and that Le(X)-containing molecules bind porcine sperm. 25339106 0 25 theme LewisX-containing 0:16 arg1 glycans 18:24 LewisX-containing glycans 0:24 LewisX-containing glycans on the porcine oviductal epithelium 0:60 LewisX-containing glycans on the porcine oviductal epithelium contribute to formation of the sperm reservoir. 25339106 4 26 theme Previous 512:519 arg1 results 521:527 Previous results 512:527 Previous results 512:527 Previous results indicated that Lewis trisaccharides are present in glycosphingolipids and O- and N-linked glycans of the porcine isthmus and that Le(X)-containing molecules bind porcine sperm. 25339106 1 27 theme sperm 174:178 arg1 transported 183:193 transported 183:193 transported 183:193 In many mammals, after semen deposition, a subpopulation of the sperm is transported to the lower oviduct, or isthmus, to form a functional sperm reservoir that provides sperm to fertilize oocytes. 25339106 1 27 theme sperm 174:178 arg1 subpopulation 153:165 a subpopulation 151:165 a subpopulation of the sperm 151:178 In many mammals, after semen deposition, a subpopulation of the sperm is transported to the lower oviduct, or isthmus, to form a functional sperm reservoir that provides sperm to fertilize oocytes. 25339106 7 28 theme % 1039:1039 arg1 head 1022:1025 the head 1018:1025 the head of nearly 60% of uncapacitated boar sperm 1018:1067 Assays using fluoresceinated glycans showed that 3-O-sulfated Le(X) (suLe(X)) bound to receptors localized on the head of nearly 60% of uncapacitated boar sperm but that the positional isomer 3-O-sulfo-Le(A) (suLe(A)) bound to <5% of sperm. 25339106 1 29 theme functional 239:248 arg1 reservoir 256:264 a functional sperm reservoir 237:264 a functional sperm reservoir that provides sperm to fertilize oocytes 237:305 In many mammals, after semen deposition, a subpopulation of the sperm is transported to the lower oviduct, or isthmus, to form a functional sperm reservoir that provides sperm to fertilize oocytes. 25339106 1 30 from mammals 118:124 arg1 transported 183:193 transported 183:193 transported 183:193 In many mammals, after semen deposition, a subpopulation of the sperm is transported to the lower oviduct, or isthmus, to form a functional sperm reservoir that provides sperm to fertilize oocytes. 25339106 1 30 from mammals 118:124 arg1 subpopulation 153:165 a subpopulation 151:165 a subpopulation of the sperm 151:178 In many mammals, after semen deposition, a subpopulation of the sperm is transported to the lower oviduct, or isthmus, to form a functional sperm reservoir that provides sperm to fertilize oocytes. 25339106 11 31 theme X 1544:1544 arg1 glycans 1547:1553 suLe(X) glycans 1539:1553 suLe(X) glycans 1539:1553 Blocking putative receptors on sperm with soluble Le(X) and suLe(X) glycans specifically reduced sperm binding to oviduct cells up to 61%. 25339106 4 32 located present 569:575 arg1 O- 603:604 O- 603:604 O- 603:604 Previous results indicated that Lewis trisaccharides are present in glycosphingolipids and O- and N-linked glycans of the porcine isthmus and that Le(X)-containing molecules bind porcine sperm. 25339106 4 32 located present 569:575 arg1 glycosphingolipids 580:597 glycosphingolipids 580:597 glycosphingolipids 580:597 Previous results indicated that Lewis trisaccharides are present in glycosphingolipids and O- and N-linked glycans of the porcine isthmus and that Le(X)-containing molecules bind porcine sperm. 25339106 4 32 located present 569:575 arg2 trisaccharides 550:563 Lewis trisaccharides 544:563 Lewis trisaccharides 544:563 Previous results indicated that Lewis trisaccharides are present in glycosphingolipids and O- and N-linked glycans of the porcine isthmus and that Le(X)-containing molecules bind porcine sperm. 25339106 3 33 theme sperm 426:430 arg1 lectins 443:449 lectins 443:449 lectins 443:449 It is proposed that binding of sperm receptors (lectins) to their oviductal cell ligands is accomplished by glycans. 25339106 3 33 theme sperm 426:430 arg1 receptors 432:440 sperm receptors 426:440 sperm receptors (lectins) 426:450 It is proposed that binding of sperm receptors (lectins) to their oviductal cell ligands is accomplished by glycans. 25339106 1 34 theme sperm 250:254 arg1 reservoir 256:264 a functional sperm reservoir 237:264 a functional sperm reservoir that provides sperm to fertilize oocytes 237:305 In many mammals, after semen deposition, a subpopulation of the sperm is transported to the lower oviduct, or isthmus, to form a functional sperm reservoir that provides sperm to fertilize oocytes. 25339106 2 35 theme precise 312:318 arg1 unclear 386:392 unclear 386:392 unclear 386:392 The precise molecular interactions that allow formation of this reservoir are unclear. 25339106 2 35 theme precise 312:318 arg1 interactions 330:341 The precise molecular interactions 308:341 The precise molecular interactions that allow formation of this reservoir 308:380 The precise molecular interactions that allow formation of this reservoir are unclear. 25339106 11 36 with sperm 1510:1514 arg1 glycans 1547:1553 suLe(X) glycans 1539:1553 suLe(X) glycans 1539:1553 Blocking putative receptors on sperm with soluble Le(X) and suLe(X) glycans specifically reduced sperm binding to oviduct cells up to 61%. 25339106 11 36 with sperm 1510:1514 arg1 X 1532:1532 X 1532:1532 X 1532:1532 Blocking putative receptors on sperm with soluble Le(X) and suLe(X) glycans specifically reduced sperm binding to oviduct cells up to 61%. 25339106 11 36 with sperm 1510:1514 arg1 Le 1529:1530 soluble Le 1521:1530 soluble Le(X) 1521:1533 Blocking putative receptors on sperm with soluble Le(X) and suLe(X) glycans specifically reduced sperm binding to oviduct cells up to 61%. 25339106 1 37 theme semen 133:137 arg1 deposition 139:148 semen deposition 133:148 semen deposition 133:148 In many mammals, after semen deposition, a subpopulation of the sperm is transported to the lower oviduct, or isthmus, to form a functional sperm reservoir that provides sperm to fertilize oocytes. 25339106 0 38 theme oviductal 41:49 arg1 epithelium 51:60 the porcine oviductal epithelium 29:60 the porcine oviductal epithelium 29:60 LewisX-containing glycans on the porcine oviductal epithelium contribute to formation of the sperm reservoir. 25339106 11 39 theme sperm 1576:1580 arg1 binding 1582:1588 sperm binding 1576:1588 sperm binding to oviduct cells up to 61% 1576:1615 Blocking putative receptors on sperm with soluble Le(X) and suLe(X) glycans specifically reduced sperm binding to oviduct cells up to 61%. 25339106 7 40 dep 3-O-sulfo-Le 1100:1111 arg1 A 1122:1122 A 1122:1122 A 1122:1122 Assays using fluoresceinated glycans showed that 3-O-sulfated Le(X) (suLe(X)) bound to receptors localized on the head of nearly 60% of uncapacitated boar sperm but that the positional isomer 3-O-sulfo-Le(A) (suLe(A)) bound to <5% of sperm. 25339106 7 40 dep 3-O-sulfo-Le 1100:1111 arg1 suLe 1117:1120 suLe 1117:1120 suLe(A) 1117:1123 Assays using fluoresceinated glycans showed that 3-O-sulfated Le(X) (suLe(X)) bound to receptors localized on the head of nearly 60% of uncapacitated boar sperm but that the positional isomer 3-O-sulfo-Le(A) (suLe(A)) bound to <5% of sperm. 25339106 4 41 attach present 569:575 arg1 O- 603:604 O- 603:604 O- 603:604 Previous results indicated that Lewis trisaccharides are present in glycosphingolipids and O- and N-linked glycans of the porcine isthmus and that Le(X)-containing molecules bind porcine sperm. 25339106 4 41 attach present 569:575 arg1 glycosphingolipids 580:597 glycosphingolipids 580:597 glycosphingolipids 580:597 Previous results indicated that Lewis trisaccharides are present in glycosphingolipids and O- and N-linked glycans of the porcine isthmus and that Le(X)-containing molecules bind porcine sperm. 25339106 4 41 attach present 569:575 arg2 trisaccharides 550:563 Lewis trisaccharides 544:563 Lewis trisaccharides 544:563 Previous results indicated that Lewis trisaccharides are present in glycosphingolipids and O- and N-linked glycans of the porcine isthmus and that Le(X)-containing molecules bind porcine sperm. 25339106 4 42 theme porcine 634:640 arg1 isthmus 642:648 the porcine isthmus 630:648 the porcine isthmus 630:648 Previous results indicated that Lewis trisaccharides are present in glycosphingolipids and O- and N-linked glycans of the porcine isthmus and that Le(X)-containing molecules bind porcine sperm. 25339106 11 43 theme oviduct 1593:1599 arg1 cells 1601:1605 oviduct cells 1593:1605 oviduct cells 1593:1605 Blocking putative receptors on sperm with soluble Le(X) and suLe(X) glycans specifically reduced sperm binding to oviduct cells up to 61%. 25339106 0 44 theme porcine 33:39 arg1 epithelium 51:60 the porcine oviductal epithelium 29:60 the porcine oviductal epithelium 29:60 LewisX-containing glycans on the porcine oviductal epithelium contribute to formation of the sperm reservoir. 25339106 6 45 theme luminal 877:883 arg1 border 885:890 the luminal border 873:890 the luminal border of the isthmus 873:905 These motifs were localized to the luminal border of the isthmus. 25339106 10 46 theme aggregates 1392:1401 arg1 Pretreatment 1363:1374 Pretreatment 1363:1374 Pretreatment of oviduct cell aggregates with the Le(X) antibody 1363:1425 Pretreatment of oviduct cell aggregates with the Le(X) antibody blocked 57% of sperm binding to isthmic aggregates. 25339106 5 47 theme Lewis 810:814 arg1 X 816:816 Lewis X 810:816 Lewis X (Le(X)) trisaccharides 810:839 Immunohistochemistry indicated that the Lewis structures identified by mass spectrometry were, in fact, Lewis X (Le(X)) trisaccharides. 25339106 2 48 theme reservoir 372:380 arg1 formation 354:362 formation 354:362 formation of this reservoir 354:380 The precise molecular interactions that allow formation of this reservoir are unclear. 25339106 10 49 theme cell 1387:1390 arg1 aggregates 1392:1401 oviduct cell aggregates 1379:1401 oviduct cell aggregates 1379:1401 Pretreatment of oviduct cell aggregates with the Le(X) antibody blocked 57% of sperm binding to isthmic aggregates. 25339106 7 50 dep Le 970:971 arg1 suLe 977:980 suLe 977:980 suLe(X) 977:983 Assays using fluoresceinated glycans showed that 3-O-sulfated Le(X) (suLe(X)) bound to receptors localized on the head of nearly 60% of uncapacitated boar sperm but that the positional isomer 3-O-sulfo-Le(A) (suLe(A)) bound to <5% of sperm. 25339106 7 50 dep Le 970:971 arg1 X 982:982 X 982:982 X 982:982 Assays using fluoresceinated glycans showed that 3-O-sulfated Le(X) (suLe(X)) bound to receptors localized on the head of nearly 60% of uncapacitated boar sperm but that the positional isomer 3-O-sulfo-Le(A) (suLe(A)) bound to <5% of sperm. 25339106 12 51 theme sperm 1793:1797 arg1 reservoir 1799:1807 the sperm reservoir 1789:1807 the sperm reservoir 1789:1807 These results demonstrate that the oviduct isthmus contains Le(X)-related moieties and that sperm binding to these oviduct glycans is necessary and sufficient for forming the sperm reservoir. 25339106 5 52 dep X 816:816 arg1 X 822:822 X 822:822 X 822:822 Immunohistochemistry indicated that the Lewis structures identified by mass spectrometry were, in fact, Lewis X (Le(X)) trisaccharides. 25339106 5 52 dep X 816:816 arg1 Le 819:820 Le 819:820 Le(X) 819:823 Immunohistochemistry indicated that the Lewis structures identified by mass spectrometry were, in fact, Lewis X (Le(X)) trisaccharides. 25339106 7 53 theme 3-O-sulfated 957:968 arg1 X 973:973 X 973:973 X 973:973 Assays using fluoresceinated glycans showed that 3-O-sulfated Le(X) (suLe(X)) bound to receptors localized on the head of nearly 60% of uncapacitated boar sperm but that the positional isomer 3-O-sulfo-Le(A) (suLe(A)) bound to <5% of sperm. 25339106 7 53 theme 3-O-sulfated 957:968 arg1 Le 970:971 3-O-sulfated Le 957:971 3-O-sulfated Le(X) (suLe(X)) 957:984 Assays using fluoresceinated glycans showed that 3-O-sulfated Le(X) (suLe(X)) bound to receptors localized on the head of nearly 60% of uncapacitated boar sperm but that the positional isomer 3-O-sulfo-Le(A) (suLe(A)) bound to <5% of sperm. 25339106 1 54 theme many 113:116 arg1 mammals 118:124 many mammals 113:124 many mammals 113:124 In many mammals, after semen deposition, a subpopulation of the sperm is transported to the lower oviduct, or isthmus, to form a functional sperm reservoir that provides sperm to fertilize oocytes. 25339106 10 55 theme oviduct 1379:1385 arg1 aggregates 1392:1401 oviduct cell aggregates 1379:1401 oviduct cell aggregates 1379:1401 Pretreatment of oviduct cell aggregates with the Le(X) antibody blocked 57% of sperm binding to isthmic aggregates. 25339106 11 56 theme suLe 1539:1542 arg1 glycans 1547:1553 suLe(X) glycans 1539:1553 suLe(X) glycans 1539:1553 Blocking putative receptors on sperm with soluble Le(X) and suLe(X) glycans specifically reduced sperm binding to oviduct cells up to 61%. 25339106 7 57 theme sperm 1142:1146 arg1 sperm 1142:1146 sperm 1142:1146 sperm 1142:1146 Assays using fluoresceinated glycans showed that 3-O-sulfated Le(X) (suLe(X)) bound to receptors localized on the head of nearly 60% of uncapacitated boar sperm but that the positional isomer 3-O-sulfo-Le(A) (suLe(A)) bound to <5% of sperm. 25339106 7 57 theme sperm 1142:1146 arg1 % 1137:1137 <5% 1135:1137 <5% of sperm 1135:1146 Assays using fluoresceinated glycans showed that 3-O-sulfated Le(X) (suLe(X)) bound to receptors localized on the head of nearly 60% of uncapacitated boar sperm but that the positional isomer 3-O-sulfo-Le(A) (suLe(A)) bound to <5% of sperm. 25339106 11 58 theme soluble 1521:1527 arg1 X 1532:1532 X 1532:1532 X 1532:1532 Blocking putative receptors on sperm with soluble Le(X) and suLe(X) glycans specifically reduced sperm binding to oviduct cells up to 61%. 25339106 11 58 theme soluble 1521:1527 arg1 Le 1529:1530 soluble Le 1521:1530 soluble Le(X) 1521:1533 Blocking putative receptors on sperm with soluble Le(X) and suLe(X) glycans specifically reduced sperm binding to oviduct cells up to 61%. 25339106 10 59 theme sperm 1442:1446 arg1 sperm 1442:1446 sperm 1442:1446 sperm binding to isthmic aggregates 1442:1476 Pretreatment of oviduct cell aggregates with the Le(X) antibody blocked 57% of sperm binding to isthmic aggregates. 25339106 10 59 theme sperm 1442:1446 arg1 % 1437:1437 57% 1435:1437 57% of sperm binding to isthmic aggregates 1435:1476 Pretreatment of oviduct cell aggregates with the Le(X) antibody blocked 57% of sperm binding to isthmic aggregates. 25339106 11 60 from receptors 1497:1505 arg1 sperm 1510:1514 sperm 1510:1514 sperm with soluble Le(X) and suLe(X) glycans 1510:1553 Blocking putative receptors on sperm with soluble Le(X) and suLe(X) glycans specifically reduced sperm binding to oviduct cells up to 61%. 25339106 1 61 from transported 183:193 arg1 mammals 118:124 many mammals 113:124 many mammals 113:124 In many mammals, after semen deposition, a subpopulation of the sperm is transported to the lower oviduct, or isthmus, to form a functional sperm reservoir that provides sperm to fertilize oocytes. 25339106 1 62 theme lower 202:206 arg1 oviduct 208:214 the lower oviduct 198:214 the lower oviduct 198:214 In many mammals, after semen deposition, a subpopulation of the sperm is transported to the lower oviduct, or isthmus, to form a functional sperm reservoir that provides sperm to fertilize oocytes. 25339106 10 63 with Pretreatment 1363:1374 arg1 antibody 1418:1425 the Le(X) antibody 1408:1425 the Le(X) antibody 1408:1425 Pretreatment of oviduct cell aggregates with the Le(X) antibody blocked 57% of sperm binding to isthmic aggregates. 25339106 12 64 theme oviduct 1653:1659 arg1 isthmus 1661:1667 the oviduct isthmus 1649:1667 the oviduct isthmus 1649:1667 These results demonstrate that the oviduct isthmus contains Le(X)-related moieties and that sperm binding to these oviduct glycans is necessary and sufficient for forming the sperm reservoir. 25339106 4 65 link N-linked 610:617 arg1 glycans 619:625 N-linked glycans 610:625 N-linked glycans 610:625 Previous results indicated that Lewis trisaccharides are present in glycosphingolipids and O- and N-linked glycans of the porcine isthmus and that Le(X)-containing molecules bind porcine sperm. 25339106 4 66 theme -containing 664:674 arg1 molecules 676:684 Le(X)-containing molecules 659:684 Le(X)-containing molecules 659:684 Previous results indicated that Lewis trisaccharides are present in glycosphingolipids and O- and N-linked glycans of the porcine isthmus and that Le(X)-containing molecules bind porcine sperm. 25339106 12 67 theme sperm 1710:1714 arg1 binding 1716:1722 sperm binding 1710:1722 sperm binding to these oviduct glycans 1710:1747 These results demonstrate that the oviduct isthmus contains Le(X)-related moieties and that sperm binding to these oviduct glycans is necessary and sufficient for forming the sperm reservoir. 25339106 4 68 theme N-linked 610:617 arg1 glycans 619:625 N-linked glycans 610:625 N-linked glycans 610:625 Previous results indicated that Lewis trisaccharides are present in glycosphingolipids and O- and N-linked glycans of the porcine isthmus and that Le(X)-containing molecules bind porcine sperm. 25339106 12 69 contain contains 1669:1676 arg1 isthmus 1661:1667 the oviduct isthmus 1649:1667 the oviduct isthmus 1649:1667 These results demonstrate that the oviduct isthmus contains Le(X)-related moieties and that sperm binding to these oviduct glycans is necessary and sufficient for forming the sperm reservoir. 25339106 12 69 contain contains 1669:1676 arg2 moieties 1692:1699 Le(X)-related moieties 1678:1699 Le(X)-related moieties 1678:1699 These results demonstrate that the oviduct isthmus contains Le(X)-related moieties and that sperm binding to these oviduct glycans is necessary and sufficient for forming the sperm reservoir. 25339106 7 70 theme fluoresceinated 921:935 arg1 glycans 937:943 fluoresceinated glycans 921:943 fluoresceinated glycans 921:943 Assays using fluoresceinated glycans showed that 3-O-sulfated Le(X) (suLe(X)) bound to receptors localized on the head of nearly 60% of uncapacitated boar sperm but that the positional isomer 3-O-sulfo-Le(A) (suLe(A)) bound to <5% of sperm. 25339106 3 71 theme cell 471:474 arg1 ligands 476:482 their oviductal cell ligands 455:482 their oviductal cell ligands 455:482 It is proposed that binding of sperm receptors (lectins) to their oviductal cell ligands is accomplished by glycans. 25339106 4 72 from glycosphingolipids 580:597 arg1 present 569:575 present 569:575 present 569:575 Previous results indicated that Lewis trisaccharides are present in glycosphingolipids and O- and N-linked glycans of the porcine isthmus and that Le(X)-containing molecules bind porcine sperm. 25339106 4 73 from O- 603:604 arg1 present 569:575 present 569:575 present 569:575 Previous results indicated that Lewis trisaccharides are present in glycosphingolipids and O- and N-linked glycans of the porcine isthmus and that Le(X)-containing molecules bind porcine sperm. 25339106 7 74 theme uncapacitated 1044:1056 arg1 sperm 1063:1067 uncapacitated boar sperm 1044:1067 uncapacitated boar sperm 1044:1067 Assays using fluoresceinated glycans showed that 3-O-sulfated Le(X) (suLe(X)) bound to receptors localized on the head of nearly 60% of uncapacitated boar sperm but that the positional isomer 3-O-sulfo-Le(A) (suLe(A)) bound to <5% of sperm. 25339106 11 75 theme putative 1488:1495 arg1 receptors 1497:1505 putative receptors 1488:1505 putative receptors on sperm with soluble Le(X) and suLe(X) glycans 1488:1553 Blocking putative receptors on sperm with soluble Le(X) and suLe(X) glycans specifically reduced sperm binding to oviduct cells up to 61%. 24909983 0 0 from IgG-Fc-fucosylation 13:31 arg1 pregnancy 36:44 pregnancy 36:44 pregnancy 36:44 Low anti-RhD IgG-Fc-fucosylation in pregnancy: a new variable predicting severity in haemolytic disease of the fetus and newborn. 24909983 4 1 from glycan 731:736 arg1 IgG-Fc-region 761:773 the IgG-Fc-region 757:773 the IgG-Fc-region 757:773 Binding of IgG to FcγR requires the N-linked glycan at position 297 in the IgG-Fc-region, consisting of several different glycoforms. 24909983 5 2 theme IgG-derived 857:867 arg1 glycopeptides 869:881 IgG-derived glycopeptides 857:881 IgG-derived glycopeptides 857:881 We therefore systematically analysed IgG-derived glycopeptides by mass spectrometry from 70 anti-D IgG1 antibodies purified from the plasma of alloimmunized pregnant women. 24909983 2 3 theme diagnostically-applied 474:495 arg1 test 573:576 a sensitive test 561:576 a sensitive test with relatively low specificity 561:608 Clinical severity is not strictly related to titre and is more accurately predicted by the diagnostically-applied monocyte-based antibody-dependent cellular cytotoxicity (ADCC), a sensitive test with relatively low specificity. 24909983 2 3 theme diagnostically-applied 474:495 arg1 ADCC 554:557 ADCC 554:557 ADCC 554:557 Clinical severity is not strictly related to titre and is more accurately predicted by the diagnostically-applied monocyte-based antibody-dependent cellular cytotoxicity (ADCC), a sensitive test with relatively low specificity. 24909983 2 3 theme diagnostically-applied 474:495 arg1 cytotoxicity 540:551 the diagnostically-applied monocyte-based antibody-dependent cellular cytotoxicity 470:551 the diagnostically-applied monocyte-based antibody-dependent cellular cytotoxicity (ADCC) 470:558 Clinical severity is not strictly related to titre and is more accurately predicted by the diagnostically-applied monocyte-based antibody-dependent cellular cytotoxicity (ADCC), a sensitive test with relatively low specificity. 24909983 8 4 theme haemoglobin 1461:1471 arg1 levels 1473:1478 low fetal-neonatal haemoglobin levels 1442:1478 low fetal-neonatal haemoglobin levels 1442:1478 Additionally, low anti-D fucosylation correlated significantly with low fetal-neonatal haemoglobin levels, thus with increased haemolysis, suggesting IgG-fucosylation to be an important pathological feature in HDFN with diagnostic potential. 24909983 0 5 dep fetus 111:115 arg1 the 107:109 the 107:109 the 107:109 Low anti-RhD IgG-Fc-fucosylation in pregnancy: a new variable predicting severity in haemolytic disease of the fetus and newborn. 24909983 1 6 theme red 228:230 arg1 antibodies 276:285 often anti-RhD (anti-D) antibodies 252:285 often anti-RhD (anti-D) antibodies 252:285 Haemolytic disease of the fetus and newborn (HDFN) may occur when maternal IgG antibodies against red blood cells (RBCs), often anti-RhD (anti-D) antibodies, cross the placenta and mediate the destruction of RBCs via phagocytic IgG-Fc-receptors (FcγR). 24909983 1 6 theme red 228:230 arg1 RBCs 245:248 RBCs 245:248 RBCs 245:248 Haemolytic disease of the fetus and newborn (HDFN) may occur when maternal IgG antibodies against red blood cells (RBCs), often anti-RhD (anti-D) antibodies, cross the placenta and mediate the destruction of RBCs via phagocytic IgG-Fc-receptors (FcγR). 24909983 1 6 theme red 228:230 arg1 cells 238:242 red blood cells 228:242 red blood cells (RBCs) 228:249 Haemolytic disease of the fetus and newborn (HDFN) may occur when maternal IgG antibodies against red blood cells (RBCs), often anti-RhD (anti-D) antibodies, cross the placenta and mediate the destruction of RBCs via phagocytic IgG-Fc-receptors (FcγR). 24909983 5 7 theme alloimmunized 963:975 arg1 women 986:990 alloimmunized pregnant women 963:990 alloimmunized pregnant women 963:990 We therefore systematically analysed IgG-derived glycopeptides by mass spectrometry from 70 anti-D IgG1 antibodies purified from the plasma of alloimmunized pregnant women. 24909983 1 8 dep fetus 156:160 arg1 the 152:154 the 152:154 the 152:154 Haemolytic disease of the fetus and newborn (HDFN) may occur when maternal IgG antibodies against red blood cells (RBCs), often anti-RhD (anti-D) antibodies, cross the placenta and mediate the destruction of RBCs via phagocytic IgG-Fc-receptors (FcγR). 24909983 7 9 theme human 1358:1362 arg1 FcγRIIIa 1364:1371 human FcγRIIIa 1358:1371 human FcγRIIIa 1358:1371 The degree of anti-D fucosylation correlated significantly with CD16 (FcγRIIIa)-mediated ADCC, in agreement with increased affinity of defucosylated IgG to human FcγRIIIa. 24909983 8 10 theme important 1550:1558 arg1 feature 1573:1579 an important pathological feature 1547:1579 an important pathological feature in HDFN with diagnostic potential 1547:1613 Additionally, low anti-D fucosylation correlated significantly with low fetal-neonatal haemoglobin levels, thus with increased haemolysis, suggesting IgG-fucosylation to be an important pathological feature in HDFN with diagnostic potential. 24909983 1 11 theme blood 232:236 arg1 antibodies 276:285 often anti-RhD (anti-D) antibodies 252:285 often anti-RhD (anti-D) antibodies 252:285 Haemolytic disease of the fetus and newborn (HDFN) may occur when maternal IgG antibodies against red blood cells (RBCs), often anti-RhD (anti-D) antibodies, cross the placenta and mediate the destruction of RBCs via phagocytic IgG-Fc-receptors (FcγR). 24909983 1 11 theme blood 232:236 arg1 RBCs 245:248 RBCs 245:248 RBCs 245:248 Haemolytic disease of the fetus and newborn (HDFN) may occur when maternal IgG antibodies against red blood cells (RBCs), often anti-RhD (anti-D) antibodies, cross the placenta and mediate the destruction of RBCs via phagocytic IgG-Fc-receptors (FcγR). 24909983 1 11 theme blood 232:236 arg1 cells 238:242 red blood cells 228:242 red blood cells (RBCs) 228:249 Haemolytic disease of the fetus and newborn (HDFN) may occur when maternal IgG antibodies against red blood cells (RBCs), often anti-RhD (anti-D) antibodies, cross the placenta and mediate the destruction of RBCs via phagocytic IgG-Fc-receptors (FcγR). 24909983 0 12 theme haemolytic 85:94 arg1 disease 96:102 haemolytic disease 85:102 haemolytic disease of the fetus and newborn 85:127 Low anti-RhD IgG-Fc-fucosylation in pregnancy: a new variable predicting severity in haemolytic disease of the fetus and newborn. 24909983 3 13 theme HDFN 680:683 arg1 pathogenesis 664:675 the pathogenesis 660:675 the pathogenesis of HDFN 660:683 This suggests that other factors are involved in the pathogenesis of HDFN. 24909983 6 14 theme IgG1 1072:1075 arg1 majority 1053:1060 the majority 1049:1060 the majority of anti-D IgG1 (even down to 12%) 1049:1094 This revealed a variable decrease in Fc-fucosylation in the majority of anti-D IgG1 (even down to 12%), whereas the total IgG of these patients remained highly fucosylated, like in healthy individuals (>90%). 24909983 8 15 theme diagnostic 1594:1603 arg1 potential 1605:1613 diagnostic potential 1594:1613 diagnostic potential 1594:1613 Additionally, low anti-D fucosylation correlated significantly with low fetal-neonatal haemoglobin levels, thus with increased haemolysis, suggesting IgG-fucosylation to be an important pathological feature in HDFN with diagnostic potential. 24909983 7 16 with agreement 1300:1308 arg1 affinity 1325:1332 increased affinity 1315:1332 increased affinity of defucosylated IgG to human FcγRIIIa 1315:1371 The degree of anti-D fucosylation correlated significantly with CD16 (FcγRIIIa)-mediated ADCC, in agreement with increased affinity of defucosylated IgG to human FcγRIIIa. 24909983 2 17 theme low 594:596 arg1 specificity 598:608 relatively low specificity 583:608 relatively low specificity 583:608 Clinical severity is not strictly related to titre and is more accurately predicted by the diagnostically-applied monocyte-based antibody-dependent cellular cytotoxicity (ADCC), a sensitive test with relatively low specificity. 24909983 4 18 theme N-linked 722:729 arg1 glycan 731:736 the N-linked glycan 718:736 the N-linked glycan at position 297 in the IgG-Fc-region, consisting of several different glycoforms 718:817 Binding of IgG to FcγR requires the N-linked glycan at position 297 in the IgG-Fc-region, consisting of several different glycoforms. 24909983 5 19 gly glycopeptides 869:881 arg2 glycopeptides 869:881 IgG-derived glycopeptides 857:881 IgG-derived glycopeptides 857:881 We therefore systematically analysed IgG-derived glycopeptides by mass spectrometry from 70 anti-D IgG1 antibodies purified from the plasma of alloimmunized pregnant women. 24909983 1 20 theme fetus 156:160 arg1 disease 141:147 Haemolytic disease 130:147 Haemolytic disease of the fetus and newborn (HDFN) 130:179 Haemolytic disease of the fetus and newborn (HDFN) may occur when maternal IgG antibodies against red blood cells (RBCs), often anti-RhD (anti-D) antibodies, cross the placenta and mediate the destruction of RBCs via phagocytic IgG-Fc-receptors (FcγR). 24909983 6 21 from decrease 1018:1025 arg1 Fc-fucosylation 1030:1044 Fc-fucosylation 1030:1044 Fc-fucosylation 1030:1044 This revealed a variable decrease in Fc-fucosylation in the majority of anti-D IgG1 (even down to 12%), whereas the total IgG of these patients remained highly fucosylated, like in healthy individuals (>90%). 24909983 6 21 from decrease 1018:1025 arg1 majority 1053:1060 the majority 1049:1060 the majority of anti-D IgG1 (even down to 12%) 1049:1094 This revealed a variable decrease in Fc-fucosylation in the majority of anti-D IgG1 (even down to 12%), whereas the total IgG of these patients remained highly fucosylated, like in healthy individuals (>90%). 24909983 6 22 theme total 1109:1113 arg1 IgG 1115:1117 the total IgG 1105:1117 the total IgG of these patients 1105:1135 This revealed a variable decrease in Fc-fucosylation in the majority of anti-D IgG1 (even down to 12%), whereas the total IgG of these patients remained highly fucosylated, like in healthy individuals (>90%). 24909983 6 23 theme anti-D 1065:1070 arg1 IgG1 1072:1075 anti-D IgG1 1065:1075 anti-D IgG1 (even down to 12%) 1065:1094 This revealed a variable decrease in Fc-fucosylation in the majority of anti-D IgG1 (even down to 12%), whereas the total IgG of these patients remained highly fucosylated, like in healthy individuals (>90%). 24909983 6 23 theme anti-D 1065:1070 arg1 % 1093:1093 even down to 12% 1078:1093 even down to 12% 1078:1093 This revealed a variable decrease in Fc-fucosylation in the majority of anti-D IgG1 (even down to 12%), whereas the total IgG of these patients remained highly fucosylated, like in healthy individuals (>90%). 24909983 0 24 theme anti-RhD 4:11 arg1 IgG-Fc-fucosylation 13:31 Low anti-RhD IgG-Fc-fucosylation 0:31 Low anti-RhD IgG-Fc-fucosylation in pregnancy: a new variable predicting severity in haemolytic disease of the fetus and newborn. 0:128 Low anti-RhD IgG-Fc-fucosylation in pregnancy: a new variable predicting severity in haemolytic disease of the fetus and newborn. 24909983 1 25 dep anti-RhD 258:265 arg1 anti-D 268:273 anti-D 268:273 anti-D 268:273 Haemolytic disease of the fetus and newborn (HDFN) may occur when maternal IgG antibodies against red blood cells (RBCs), often anti-RhD (anti-D) antibodies, cross the placenta and mediate the destruction of RBCs via phagocytic IgG-Fc-receptors (FcγR). 24909983 4 26 theme different 798:806 arg1 glycoforms 808:817 several different glycoforms 790:817 several different glycoforms 790:817 Binding of IgG to FcγR requires the N-linked glycan at position 297 in the IgG-Fc-region, consisting of several different glycoforms. 24909983 6 27 dep 12 1091:1092 arg1 to 1088:1089 to 1088:1089 to 1088:1089 This revealed a variable decrease in Fc-fucosylation in the majority of anti-D IgG1 (even down to 12%), whereas the total IgG of these patients remained highly fucosylated, like in healthy individuals (>90%). 24909983 1 28 theme newborn 166:172 arg1 disease 141:147 Haemolytic disease 130:147 Haemolytic disease of the fetus and newborn (HDFN) 130:179 Haemolytic disease of the fetus and newborn (HDFN) may occur when maternal IgG antibodies against red blood cells (RBCs), often anti-RhD (anti-D) antibodies, cross the placenta and mediate the destruction of RBCs via phagocytic IgG-Fc-receptors (FcγR). 24909983 0 29 theme Low 0:2 arg1 IgG-Fc-fucosylation 13:31 Low anti-RhD IgG-Fc-fucosylation 0:31 Low anti-RhD IgG-Fc-fucosylation in pregnancy: a new variable predicting severity in haemolytic disease of the fetus and newborn. 0:128 Low anti-RhD IgG-Fc-fucosylation in pregnancy: a new variable predicting severity in haemolytic disease of the fetus and newborn. 24909983 2 30 theme sensitive 563:571 arg1 test 573:576 a sensitive test 561:576 a sensitive test with relatively low specificity 561:608 Clinical severity is not strictly related to titre and is more accurately predicted by the diagnostically-applied monocyte-based antibody-dependent cellular cytotoxicity (ADCC), a sensitive test with relatively low specificity. 24909983 2 30 theme sensitive 563:571 arg1 cytotoxicity 540:551 the diagnostically-applied monocyte-based antibody-dependent cellular cytotoxicity 470:551 the diagnostically-applied monocyte-based antibody-dependent cellular cytotoxicity (ADCC) 470:558 Clinical severity is not strictly related to titre and is more accurately predicted by the diagnostically-applied monocyte-based antibody-dependent cellular cytotoxicity (ADCC), a sensitive test with relatively low specificity. 24909983 5 31 theme anti-D 912:917 arg1 antibodies 924:933 70 anti-D IgG1 antibodies 909:933 70 anti-D IgG1 antibodies purified from the plasma of alloimmunized pregnant women 909:990 We therefore systematically analysed IgG-derived glycopeptides by mass spectrometry from 70 anti-D IgG1 antibodies purified from the plasma of alloimmunized pregnant women. 24909983 2 32 with test 573:576 arg1 specificity 598:608 relatively low specificity 583:608 relatively low specificity 583:608 Clinical severity is not strictly related to titre and is more accurately predicted by the diagnostically-applied monocyte-based antibody-dependent cellular cytotoxicity (ADCC), a sensitive test with relatively low specificity. 24909983 7 33 theme increased 1315:1323 arg1 affinity 1325:1332 increased affinity 1315:1332 increased affinity of defucosylated IgG to human FcγRIIIa 1315:1371 The degree of anti-D fucosylation correlated significantly with CD16 (FcγRIIIa)-mediated ADCC, in agreement with increased affinity of defucosylated IgG to human FcγRIIIa. 24909983 8 34 theme increased 1491:1499 arg1 haemolysis 1501:1510 increased haemolysis 1491:1510 increased haemolysis 1491:1510 Additionally, low anti-D fucosylation correlated significantly with low fetal-neonatal haemoglobin levels, thus with increased haemolysis, suggesting IgG-fucosylation to be an important pathological feature in HDFN with diagnostic potential. 24909983 2 35 theme monocyte-based 497:510 arg1 test 573:576 a sensitive test 561:576 a sensitive test with relatively low specificity 561:608 Clinical severity is not strictly related to titre and is more accurately predicted by the diagnostically-applied monocyte-based antibody-dependent cellular cytotoxicity (ADCC), a sensitive test with relatively low specificity. 24909983 2 35 theme monocyte-based 497:510 arg1 ADCC 554:557 ADCC 554:557 ADCC 554:557 Clinical severity is not strictly related to titre and is more accurately predicted by the diagnostically-applied monocyte-based antibody-dependent cellular cytotoxicity (ADCC), a sensitive test with relatively low specificity. 24909983 2 35 theme monocyte-based 497:510 arg1 cytotoxicity 540:551 the diagnostically-applied monocyte-based antibody-dependent cellular cytotoxicity 470:551 the diagnostically-applied monocyte-based antibody-dependent cellular cytotoxicity (ADCC) 470:558 Clinical severity is not strictly related to titre and is more accurately predicted by the diagnostically-applied monocyte-based antibody-dependent cellular cytotoxicity (ADCC), a sensitive test with relatively low specificity. 24909983 5 36 theme IgG1 919:922 arg1 antibodies 924:933 70 anti-D IgG1 antibodies 909:933 70 anti-D IgG1 antibodies purified from the plasma of alloimmunized pregnant women 909:990 We therefore systematically analysed IgG-derived glycopeptides by mass spectrometry from 70 anti-D IgG1 antibodies purified from the plasma of alloimmunized pregnant women. 24909983 7 37 theme fucosylation 1223:1234 arg1 degree 1206:1211 The degree 1202:1211 The degree of anti-D fucosylation 1202:1234 The degree of anti-D fucosylation correlated significantly with CD16 (FcγRIIIa)-mediated ADCC, in agreement with increased affinity of defucosylated IgG to human FcγRIIIa. 24909983 7 38 theme defucosylated 1337:1349 arg1 IgG 1351:1353 defucosylated IgG 1337:1353 defucosylated IgG 1337:1353 The degree of anti-D fucosylation correlated significantly with CD16 (FcγRIIIa)-mediated ADCC, in agreement with increased affinity of defucosylated IgG to human FcγRIIIa. 24909983 0 39 theme fetus 111:115 arg1 disease 96:102 haemolytic disease 85:102 haemolytic disease of the fetus and newborn 85:127 Low anti-RhD IgG-Fc-fucosylation in pregnancy: a new variable predicting severity in haemolytic disease of the fetus and newborn. 24909983 4 40 theme IgG 697:699 arg1 Binding 686:692 Binding 686:692 Binding of IgG to FcγR 686:707 Binding of IgG to FcγR requires the N-linked glycan at position 297 in the IgG-Fc-region, consisting of several different glycoforms. 24909983 6 41 dep revealed 998:1005 arg1 whereas 1097:1103 whereas 1097:1103 whereas 1097:1103 This revealed a variable decrease in Fc-fucosylation in the majority of anti-D IgG1 (even down to 12%), whereas the total IgG of these patients remained highly fucosylated, like in healthy individuals (>90%). 24909983 6 42 theme healthy 1174:1180 arg1 individuals 1182:1192 healthy individuals 1174:1192 healthy individuals (>90%) 1174:1199 This revealed a variable decrease in Fc-fucosylation in the majority of anti-D IgG1 (even down to 12%), whereas the total IgG of these patients remained highly fucosylated, like in healthy individuals (>90%). 24909983 6 42 theme healthy 1174:1180 arg1 % 1198:1198 >90% 1195:1198 >90% 1195:1198 This revealed a variable decrease in Fc-fucosylation in the majority of anti-D IgG1 (even down to 12%), whereas the total IgG of these patients remained highly fucosylated, like in healthy individuals (>90%). 24909983 8 43 from feature 1573:1579 arg1 HDFN 1584:1587 HDFN 1584:1587 HDFN with diagnostic potential 1584:1613 Additionally, low anti-D fucosylation correlated significantly with low fetal-neonatal haemoglobin levels, thus with increased haemolysis, suggesting IgG-fucosylation to be an important pathological feature in HDFN with diagnostic potential. 24909983 0 44 theme newborn 121:127 arg1 disease 96:102 haemolytic disease 85:102 haemolytic disease of the fetus and newborn 85:127 Low anti-RhD IgG-Fc-fucosylation in pregnancy: a new variable predicting severity in haemolytic disease of the fetus and newborn. 24909983 8 45 theme low 1388:1390 arg1 fucosylation 1399:1410 low anti-D fucosylation 1388:1410 low anti-D fucosylation 1388:1410 Additionally, low anti-D fucosylation correlated significantly with low fetal-neonatal haemoglobin levels, thus with increased haemolysis, suggesting IgG-fucosylation to be an important pathological feature in HDFN with diagnostic potential. 24909983 6 46 theme variable 1009:1016 arg1 decrease 1018:1025 a variable decrease 1007:1025 a variable decrease in Fc-fucosylation in the majority of anti-D IgG1 (even down to 12%) 1007:1094 This revealed a variable decrease in Fc-fucosylation in the majority of anti-D IgG1 (even down to 12%), whereas the total IgG of these patients remained highly fucosylated, like in healthy individuals (>90%). 24909983 0 47 theme new 49:51 arg1 variable 53:60 a new variable 47:60 Low anti-RhD IgG-Fc-fucosylation in pregnancy: a new variable predicting severity in haemolytic disease of the fetus and newborn. 0:128 Low anti-RhD IgG-Fc-fucosylation in pregnancy: a new variable predicting severity in haemolytic disease of the fetus and newborn. 24909983 1 48 theme anti-RhD 258:265 arg1 antibodies 276:285 often anti-RhD (anti-D) antibodies 252:285 often anti-RhD (anti-D) antibodies 252:285 Haemolytic disease of the fetus and newborn (HDFN) may occur when maternal IgG antibodies against red blood cells (RBCs), often anti-RhD (anti-D) antibodies, cross the placenta and mediate the destruction of RBCs via phagocytic IgG-Fc-receptors (FcγR). 24909983 1 48 theme anti-RhD 258:265 arg1 cells 238:242 red blood cells 228:242 red blood cells (RBCs) 228:249 Haemolytic disease of the fetus and newborn (HDFN) may occur when maternal IgG antibodies against red blood cells (RBCs), often anti-RhD (anti-D) antibodies, cross the placenta and mediate the destruction of RBCs via phagocytic IgG-Fc-receptors (FcγR). 24909983 1 49 theme RBCs 338:341 arg1 destruction 323:333 the destruction 319:333 the destruction of RBCs 319:341 Haemolytic disease of the fetus and newborn (HDFN) may occur when maternal IgG antibodies against red blood cells (RBCs), often anti-RhD (anti-D) antibodies, cross the placenta and mediate the destruction of RBCs via phagocytic IgG-Fc-receptors (FcγR). 24909983 0 50 gly IgG-Fc-fucosylation 13:31 arg1 pregnancy 36:44 pregnancy 36:44 pregnancy 36:44 Low anti-RhD IgG-Fc-fucosylation in pregnancy: a new variable predicting severity in haemolytic disease of the fetus and newborn. 24909983 4 51 theme several 790:796 arg1 glycoforms 808:817 several different glycoforms 790:817 several different glycoforms 790:817 Binding of IgG to FcγR requires the N-linked glycan at position 297 in the IgG-Fc-region, consisting of several different glycoforms. 24909983 4 52 link N-linked 722:729 arg1 glycan 731:736 the N-linked glycan 718:736 the N-linked glycan at position 297 in the IgG-Fc-region, consisting of several different glycoforms 718:817 Binding of IgG to FcγR requires the N-linked glycan at position 297 in the IgG-Fc-region, consisting of several different glycoforms. 24909983 8 53 theme fetal-neonatal 1446:1459 arg1 levels 1473:1478 low fetal-neonatal haemoglobin levels 1442:1478 low fetal-neonatal haemoglobin levels 1442:1478 Additionally, low anti-D fucosylation correlated significantly with low fetal-neonatal haemoglobin levels, thus with increased haemolysis, suggesting IgG-fucosylation to be an important pathological feature in HDFN with diagnostic potential. 24909983 5 54 link IgG-derived 857:867 arg1 glycopeptides 869:881 IgG-derived glycopeptides 857:881 IgG-derived glycopeptides 857:881 We therefore systematically analysed IgG-derived glycopeptides by mass spectrometry from 70 anti-D IgG1 antibodies purified from the plasma of alloimmunized pregnant women. 24909983 3 55 theme other 630:634 arg1 factors 636:642 other factors 630:642 other factors 630:642 This suggests that other factors are involved in the pathogenesis of HDFN. 24909983 8 56 theme anti-D 1392:1397 arg1 fucosylation 1399:1410 low anti-D fucosylation 1388:1410 low anti-D fucosylation 1388:1410 Additionally, low anti-D fucosylation correlated significantly with low fetal-neonatal haemoglobin levels, thus with increased haemolysis, suggesting IgG-fucosylation to be an important pathological feature in HDFN with diagnostic potential. 24909983 5 57 theme mass 886:889 arg1 spectrometry 891:902 mass spectrometry 886:902 mass spectrometry from 70 anti-D IgG1 antibodies purified from the plasma of alloimmunized pregnant women 886:990 We therefore systematically analysed IgG-derived glycopeptides by mass spectrometry from 70 anti-D IgG1 antibodies purified from the plasma of alloimmunized pregnant women. 24909983 8 58 with HDFN 1584:1587 arg1 potential 1605:1613 diagnostic potential 1594:1613 diagnostic potential 1594:1613 Additionally, low anti-D fucosylation correlated significantly with low fetal-neonatal haemoglobin levels, thus with increased haemolysis, suggesting IgG-fucosylation to be an important pathological feature in HDFN with diagnostic potential. 24909983 6 59 theme patients 1128:1135 arg1 IgG 1115:1117 the total IgG 1105:1117 the total IgG of these patients 1105:1135 This revealed a variable decrease in Fc-fucosylation in the majority of anti-D IgG1 (even down to 12%), whereas the total IgG of these patients remained highly fucosylated, like in healthy individuals (>90%). 24909983 2 60 theme cellular 531:538 arg1 test 573:576 a sensitive test 561:576 a sensitive test with relatively low specificity 561:608 Clinical severity is not strictly related to titre and is more accurately predicted by the diagnostically-applied monocyte-based antibody-dependent cellular cytotoxicity (ADCC), a sensitive test with relatively low specificity. 24909983 2 60 theme cellular 531:538 arg1 ADCC 554:557 ADCC 554:557 ADCC 554:557 Clinical severity is not strictly related to titre and is more accurately predicted by the diagnostically-applied monocyte-based antibody-dependent cellular cytotoxicity (ADCC), a sensitive test with relatively low specificity. 24909983 2 60 theme cellular 531:538 arg1 cytotoxicity 540:551 the diagnostically-applied monocyte-based antibody-dependent cellular cytotoxicity 470:551 the diagnostically-applied monocyte-based antibody-dependent cellular cytotoxicity (ADCC) 470:558 Clinical severity is not strictly related to titre and is more accurately predicted by the diagnostically-applied monocyte-based antibody-dependent cellular cytotoxicity (ADCC), a sensitive test with relatively low specificity. 24909983 1 61 theme phagocytic 347:356 arg1 FcγR 376:379 FcγR 376:379 FcγR 376:379 Haemolytic disease of the fetus and newborn (HDFN) may occur when maternal IgG antibodies against red blood cells (RBCs), often anti-RhD (anti-D) antibodies, cross the placenta and mediate the destruction of RBCs via phagocytic IgG-Fc-receptors (FcγR). 24909983 1 61 theme phagocytic 347:356 arg1 IgG-Fc-receptors 358:373 phagocytic IgG-Fc-receptors 347:373 phagocytic IgG-Fc-receptors (FcγR) 347:380 Haemolytic disease of the fetus and newborn (HDFN) may occur when maternal IgG antibodies against red blood cells (RBCs), often anti-RhD (anti-D) antibodies, cross the placenta and mediate the destruction of RBCs via phagocytic IgG-Fc-receptors (FcγR). 24909983 7 62 theme -mediated 1281:1289 arg1 ADCC 1291:1294 CD16 (FcγRIIIa)-mediated ADCC 1266:1294 CD16 (FcγRIIIa)-mediated ADCC 1266:1294 The degree of anti-D fucosylation correlated significantly with CD16 (FcγRIIIa)-mediated ADCC, in agreement with increased affinity of defucosylated IgG to human FcγRIIIa. 24909983 7 63 theme IgG 1351:1353 arg1 affinity 1325:1332 increased affinity 1315:1332 increased affinity of defucosylated IgG to human FcγRIIIa 1315:1371 The degree of anti-D fucosylation correlated significantly with CD16 (FcγRIIIa)-mediated ADCC, in agreement with increased affinity of defucosylated IgG to human FcγRIIIa. 24909983 5 64 from antibodies 924:933 arg1 spectrometry 891:902 mass spectrometry 886:902 mass spectrometry from 70 anti-D IgG1 antibodies purified from the plasma of alloimmunized pregnant women 886:990 We therefore systematically analysed IgG-derived glycopeptides by mass spectrometry from 70 anti-D IgG1 antibodies purified from the plasma of alloimmunized pregnant women. 24909983 8 65 theme pathological 1560:1571 arg1 feature 1573:1579 an important pathological feature 1547:1579 an important pathological feature in HDFN with diagnostic potential 1547:1613 Additionally, low anti-D fucosylation correlated significantly with low fetal-neonatal haemoglobin levels, thus with increased haemolysis, suggesting IgG-fucosylation to be an important pathological feature in HDFN with diagnostic potential. 24909983 2 66 theme antibody-dependent 512:529 arg1 test 573:576 a sensitive test 561:576 a sensitive test with relatively low specificity 561:608 Clinical severity is not strictly related to titre and is more accurately predicted by the diagnostically-applied monocyte-based antibody-dependent cellular cytotoxicity (ADCC), a sensitive test with relatively low specificity. 24909983 2 66 theme antibody-dependent 512:529 arg1 ADCC 554:557 ADCC 554:557 ADCC 554:557 Clinical severity is not strictly related to titre and is more accurately predicted by the diagnostically-applied monocyte-based antibody-dependent cellular cytotoxicity (ADCC), a sensitive test with relatively low specificity. 24909983 2 66 theme antibody-dependent 512:529 arg1 cytotoxicity 540:551 the diagnostically-applied monocyte-based antibody-dependent cellular cytotoxicity 470:551 the diagnostically-applied monocyte-based antibody-dependent cellular cytotoxicity (ADCC) 470:558 Clinical severity is not strictly related to titre and is more accurately predicted by the diagnostically-applied monocyte-based antibody-dependent cellular cytotoxicity (ADCC), a sensitive test with relatively low specificity. 24909983 0 67 dep IgG-Fc-fucosylation 13:31 arg1 variable 53:60 a new variable 47:60 Low anti-RhD IgG-Fc-fucosylation in pregnancy: a new variable predicting severity in haemolytic disease of the fetus and newborn. 0:128 Low anti-RhD IgG-Fc-fucosylation in pregnancy: a new variable predicting severity in haemolytic disease of the fetus and newborn. 24909983 1 68 theme maternal 196:203 arg1 antibodies 209:218 maternal IgG antibodies 196:218 maternal IgG antibodies against red blood cells (RBCs), often anti-RhD (anti-D) antibodies, 196:286 Haemolytic disease of the fetus and newborn (HDFN) may occur when maternal IgG antibodies against red blood cells (RBCs), often anti-RhD (anti-D) antibodies, cross the placenta and mediate the destruction of RBCs via phagocytic IgG-Fc-receptors (FcγR). 24909983 7 69 gly defucosylated 1337:1349 arg1 IgG 1351:1353 defucosylated IgG 1337:1353 defucosylated IgG 1337:1353 The degree of anti-D fucosylation correlated significantly with CD16 (FcγRIIIa)-mediated ADCC, in agreement with increased affinity of defucosylated IgG to human FcγRIIIa. 24909983 7 70 theme anti-D 1216:1221 arg1 fucosylation 1223:1234 anti-D fucosylation 1216:1234 anti-D fucosylation 1216:1234 The degree of anti-D fucosylation correlated significantly with CD16 (FcγRIIIa)-mediated ADCC, in agreement with increased affinity of defucosylated IgG to human FcγRIIIa. 24909983 5 71 theme pregnant 977:984 arg1 women 986:990 alloimmunized pregnant women 963:990 alloimmunized pregnant women 963:990 We therefore systematically analysed IgG-derived glycopeptides by mass spectrometry from 70 anti-D IgG1 antibodies purified from the plasma of alloimmunized pregnant women. 24909983 4 72 from position 741:748 arg1 glycan 731:736 the N-linked glycan 718:736 the N-linked glycan at position 297 in the IgG-Fc-region, consisting of several different glycoforms 718:817 Binding of IgG to FcγR requires the N-linked glycan at position 297 in the IgG-Fc-region, consisting of several different glycoforms. 24909983 1 73 theme Haemolytic 130:139 arg1 disease 141:147 Haemolytic disease 130:147 Haemolytic disease of the fetus and newborn (HDFN) 130:179 Haemolytic disease of the fetus and newborn (HDFN) may occur when maternal IgG antibodies against red blood cells (RBCs), often anti-RhD (anti-D) antibodies, cross the placenta and mediate the destruction of RBCs via phagocytic IgG-Fc-receptors (FcγR). 24909983 1 74 theme IgG 205:207 arg1 antibodies 209:218 maternal IgG antibodies 196:218 maternal IgG antibodies against red blood cells (RBCs), often anti-RhD (anti-D) antibodies, 196:286 Haemolytic disease of the fetus and newborn (HDFN) may occur when maternal IgG antibodies against red blood cells (RBCs), often anti-RhD (anti-D) antibodies, cross the placenta and mediate the destruction of RBCs via phagocytic IgG-Fc-receptors (FcγR). 24909983 8 75 theme low 1442:1444 arg1 levels 1473:1478 low fetal-neonatal haemoglobin levels 1442:1478 low fetal-neonatal haemoglobin levels 1442:1478 Additionally, low anti-D fucosylation correlated significantly with low fetal-neonatal haemoglobin levels, thus with increased haemolysis, suggesting IgG-fucosylation to be an important pathological feature in HDFN with diagnostic potential. 24909983 5 76 theme women 986:990 arg1 plasma 953:958 the plasma 949:958 the plasma of alloimmunized pregnant women 949:990 We therefore systematically analysed IgG-derived glycopeptides by mass spectrometry from 70 anti-D IgG1 antibodies purified from the plasma of alloimmunized pregnant women. 24909983 2 77 theme Clinical 383:390 arg1 severity 392:399 Clinical severity 383:399 Clinical severity 383:399 Clinical severity is not strictly related to titre and is more accurately predicted by the diagnostically-applied monocyte-based antibody-dependent cellular cytotoxicity (ADCC), a sensitive test with relatively low specificity. 24509444 0 0 theme M 90:90 arg1 protein 92:98 severe acute respiratory syndrome coronavirus M protein 44:98 severe acute respiratory syndrome coronavirus M protein 44:98 Suppression of innate antiviral response by severe acute respiratory syndrome coronavirus M protein is mediated through the first transmembrane domain. 24509444 3 1 theme SARS 509:512 arg1 coronavirus 514:524 SARS coronavirus 509:524 SARS coronavirus M protein 509:534 In this study, we demonstrate that the IFN-antagonizing activity is specific to SARS coronavirus M protein and is mediated through its first transmembrane domain (TM1) located at the N terminus. 24509444 0 2 theme coronavirus 78:88 arg1 protein 92:98 severe acute respiratory syndrome coronavirus M protein 44:98 severe acute respiratory syndrome coronavirus M protein 44:98 Suppression of innate antiviral response by severe acute respiratory syndrome coronavirus M protein is mediated through the first transmembrane domain. 24509444 5 3 contain has 756:758 arg2 influence 763:771 no influence 760:771 no influence 760:771 Whereas N-linked glycosylation of SARS coronavirus M protein has no influence on IFN antagonism, TM1 is indispensable for the suppression of IFN production. 24509444 5 3 contain has 756:758 arg1 glycosylation 712:724 N-linked glycosylation 703:724 N-linked glycosylation of SARS coronavirus M protein 703:754 Whereas N-linked glycosylation of SARS coronavirus M protein has no influence on IFN antagonism, TM1 is indispensable for the suppression of IFN production. 24509444 5 4 theme IFN 776:778 arg1 antagonism 780:789 IFN antagonism 776:789 IFN antagonism 776:789 Whereas N-linked glycosylation of SARS coronavirus M protein has no influence on IFN antagonism, TM1 is indispensable for the suppression of IFN production. 24509444 3 5 theme coronavirus 514:524 arg1 protein 528:534 SARS coronavirus M protein 509:534 SARS coronavirus M protein 509:534 In this study, we demonstrate that the IFN-antagonizing activity is specific to SARS coronavirus M protein and is mediated through its first transmembrane domain (TM1) located at the N terminus. 24509444 2 6 theme coronavirus 295:305 arg1 protein 309:315 severe acute respiratory syndrome (SARS) coronavirus M protein 254:315 severe acute respiratory syndrome (SARS) coronavirus M protein 254:315 We have previously shown that severe acute respiratory syndrome (SARS) coronavirus M protein suppresses type I interferon (IFN) production by impeding the formation of functional TRAF3-containing complex. 24509444 3 7 theme first 564:568 arg1 TM1 592:594 TM1 592:594 TM1 592:594 In this study, we demonstrate that the IFN-antagonizing activity is specific to SARS coronavirus M protein and is mediated through its first transmembrane domain (TM1) located at the N terminus. 24509444 3 7 theme first 564:568 arg1 domain 584:589 its first transmembrane domain 560:589 its first transmembrane domain (TM1) located at the N terminus 560:621 In this study, we demonstrate that the IFN-antagonizing activity is specific to SARS coronavirus M protein and is mediated through its first transmembrane domain (TM1) located at the N terminus. 24509444 3 8 theme transmembrane 570:582 arg1 TM1 592:594 TM1 592:594 TM1 592:594 In this study, we demonstrate that the IFN-antagonizing activity is specific to SARS coronavirus M protein and is mediated through its first transmembrane domain (TM1) located at the N terminus. 24509444 3 8 theme transmembrane 570:582 arg1 domain 584:589 its first transmembrane domain 560:589 its first transmembrane domain (TM1) located at the N terminus 560:621 In this study, we demonstrate that the IFN-antagonizing activity is specific to SARS coronavirus M protein and is mediated through its first transmembrane domain (TM1) located at the N terminus. 24509444 5 9 link N-linked 703:710 arg1 glycosylation 712:724 N-linked glycosylation 703:724 N-linked glycosylation of SARS coronavirus M protein 703:754 Whereas N-linked glycosylation of SARS coronavirus M protein has no influence on IFN antagonism, TM1 is indispensable for the suppression of IFN production. 24509444 6 10 theme Golgi 924:928 arg1 apparatus 930:938 the Golgi apparatus 920:938 the Golgi apparatus 920:938 TM1 targets SARS coronavirus M protein and heterologous proteins to the Golgi apparatus, yet Golgi localization is required but not sufficient for IFN antagonism. 24509444 5 11 theme production 840:849 arg1 suppression 821:831 the suppression 817:831 the suppression of IFN production 817:849 Whereas N-linked glycosylation of SARS coronavirus M protein has no influence on IFN antagonism, TM1 is indispensable for the suppression of IFN production. 24509444 4 12 theme IFN 679:681 arg1 production 683:692 IFN production 679:692 IFN production 679:692 M protein from human coronavirus HKU1 does not inhibit IFN production. 24509444 6 13 theme M 881:881 arg1 protein 883:889 SARS coronavirus M protein 864:889 SARS coronavirus M protein 864:889 TM1 targets SARS coronavirus M protein and heterologous proteins to the Golgi apparatus, yet Golgi localization is required but not sufficient for IFN antagonism. 24509444 8 14 theme M 1227:1227 arg1 protein 1229:1235 SARS coronavirus M protein 1210:1235 SARS coronavirus M protein required for suppression of innate antiviral response 1210:1289 Our work defines the molecular architecture of SARS coronavirus M protein required for suppression of innate antiviral response. 24509444 8 15 theme protein 1229:1235 arg1 architecture 1194:1205 the molecular architecture 1180:1205 the molecular architecture of SARS coronavirus M protein required for suppression of innate antiviral response 1180:1289 Our work defines the molecular architecture of SARS coronavirus M protein required for suppression of innate antiviral response. 24509444 4 16 from HKU1 657:660 arg1 protein 626:632 M protein 624:632 M protein from human coronavirus HKU1 624:660 M protein from human coronavirus HKU1 does not inhibit IFN production. 24509444 1 17 theme various 181:187 arg1 measures 189:196 various measures 181:196 various measures 181:196 Coronaviruses have developed various measures to evade innate immunity. 24509444 5 18 theme M 746:746 arg1 protein 748:754 SARS coronavirus M protein 729:754 SARS coronavirus M protein 729:754 Whereas N-linked glycosylation of SARS coronavirus M protein has no influence on IFN antagonism, TM1 is indispensable for the suppression of IFN production. 24509444 6 19 theme coronavirus 869:879 arg1 protein 883:889 SARS coronavirus M protein 864:889 SARS coronavirus M protein 864:889 TM1 targets SARS coronavirus M protein and heterologous proteins to the Golgi apparatus, yet Golgi localization is required but not sufficient for IFN antagonism. 24509444 7 20 with interaction 1111:1121 arg1 effectors 1152:1160 its downstream effectors 1137:1160 its downstream effectors 1137:1160 Mechanistically, TM1 is capable of binding with RIG-I, TRAF3, TBK1 and IKKε, and preventing the interaction of TRAF3 with its downstream effectors. 24509444 4 21 theme human 639:643 arg1 HKU1 657:660 human coronavirus HKU1 639:660 human coronavirus HKU1 639:660 M protein from human coronavirus HKU1 does not inhibit IFN production. 24509444 6 22 theme SARS 864:867 arg1 protein 883:889 SARS coronavirus M protein 864:889 SARS coronavirus M protein 864:889 TM1 targets SARS coronavirus M protein and heterologous proteins to the Golgi apparatus, yet Golgi localization is required but not sufficient for IFN antagonism. 24509444 5 23 theme protein 748:754 arg1 glycosylation 712:724 N-linked glycosylation 703:724 N-linked glycosylation of SARS coronavirus M protein 703:754 Whereas N-linked glycosylation of SARS coronavirus M protein has no influence on IFN antagonism, TM1 is indispensable for the suppression of IFN production. 24509444 2 24 theme type 328:331 arg1 IFN 347:349 IFN 347:349 IFN 347:349 We have previously shown that severe acute respiratory syndrome (SARS) coronavirus M protein suppresses type I interferon (IFN) production by impeding the formation of functional TRAF3-containing complex. 24509444 2 24 theme type 328:331 arg1 interferon 335:344 type I interferon 328:344 type I interferon (IFN) production 328:361 We have previously shown that severe acute respiratory syndrome (SARS) coronavirus M protein suppresses type I interferon (IFN) production by impeding the formation of functional TRAF3-containing complex. 24509444 3 25 from terminus 614:621 arg1 located 597:603 located 597:603 located 597:603 In this study, we demonstrate that the IFN-antagonizing activity is specific to SARS coronavirus M protein and is mediated through its first transmembrane domain (TM1) located at the N terminus. 24509444 8 26 theme coronavirus 1215:1225 arg1 protein 1229:1235 SARS coronavirus M protein 1210:1235 SARS coronavirus M protein required for suppression of innate antiviral response 1210:1289 Our work defines the molecular architecture of SARS coronavirus M protein required for suppression of innate antiviral response. 24509444 6 27 theme heterologous 895:906 arg1 proteins 908:915 heterologous proteins 895:915 heterologous proteins 895:915 TM1 targets SARS coronavirus M protein and heterologous proteins to the Golgi apparatus, yet Golgi localization is required but not sufficient for IFN antagonism. 24509444 4 28 theme coronavirus 645:655 arg1 HKU1 657:660 human coronavirus HKU1 639:660 human coronavirus HKU1 639:660 M protein from human coronavirus HKU1 does not inhibit IFN production. 24509444 8 29 theme SARS 1210:1213 arg1 protein 1229:1235 SARS coronavirus M protein 1210:1235 SARS coronavirus M protein required for suppression of innate antiviral response 1210:1289 Our work defines the molecular architecture of SARS coronavirus M protein required for suppression of innate antiviral response. 24509444 0 30 theme antiviral 22:30 arg1 response 32:39 innate antiviral response 15:39 innate antiviral response 15:39 Suppression of innate antiviral response by severe acute respiratory syndrome coronavirus M protein is mediated through the first transmembrane domain. 24509444 8 31 theme antiviral 1272:1280 arg1 response 1282:1289 innate antiviral response 1265:1289 innate antiviral response 1265:1289 Our work defines the molecular architecture of SARS coronavirus M protein required for suppression of innate antiviral response. 24509444 0 32 theme first 124:128 arg1 domain 144:149 the first transmembrane domain 120:149 the first transmembrane domain 120:149 Suppression of innate antiviral response by severe acute respiratory syndrome coronavirus M protein is mediated through the first transmembrane domain. 24509444 1 33 theme innate 207:212 arg1 immunity 214:221 innate immunity 207:221 innate immunity 207:221 Coronaviruses have developed various measures to evade innate immunity. 24509444 0 34 theme innate 15:20 arg1 response 32:39 innate antiviral response 15:39 innate antiviral response 15:39 Suppression of innate antiviral response by severe acute respiratory syndrome coronavirus M protein is mediated through the first transmembrane domain. 24509444 6 35 theme Golgi 945:949 arg1 localization 951:962 Golgi localization 945:962 Golgi localization 945:962 TM1 targets SARS coronavirus M protein and heterologous proteins to the Golgi apparatus, yet Golgi localization is required but not sufficient for IFN antagonism. 24509444 2 36 theme M 307:307 arg1 protein 309:315 severe acute respiratory syndrome (SARS) coronavirus M protein 254:315 severe acute respiratory syndrome (SARS) coronavirus M protein 254:315 We have previously shown that severe acute respiratory syndrome (SARS) coronavirus M protein suppresses type I interferon (IFN) production by impeding the formation of functional TRAF3-containing complex. 24509444 3 37 theme IFN-antagonizing 468:483 arg1 specific 497:504 specific 497:504 specific 497:504 In this study, we demonstrate that the IFN-antagonizing activity is specific to SARS coronavirus M protein and is mediated through its first transmembrane domain (TM1) located at the N terminus. 24509444 3 37 theme IFN-antagonizing 468:483 arg1 activity 485:492 the IFN-antagonizing activity 464:492 the IFN-antagonizing activity 464:492 In this study, we demonstrate that the IFN-antagonizing activity is specific to SARS coronavirus M protein and is mediated through its first transmembrane domain (TM1) located at the N terminus. 24509444 5 38 theme N-linked 703:710 arg1 glycosylation 712:724 N-linked glycosylation 703:724 N-linked glycosylation of SARS coronavirus M protein 703:754 Whereas N-linked glycosylation of SARS coronavirus M protein has no influence on IFN antagonism, TM1 is indispensable for the suppression of IFN production. 24509444 2 39 theme complex 420:426 arg1 formation 379:387 the formation 375:387 the formation of functional TRAF3-containing complex 375:426 We have previously shown that severe acute respiratory syndrome (SARS) coronavirus M protein suppresses type I interferon (IFN) production by impeding the formation of functional TRAF3-containing complex. 24509444 0 40 theme response 32:39 arg1 Suppression 0:10 Suppression 0:10 Suppression of innate antiviral response by severe acute respiratory syndrome coronavirus M protein 0:98 Suppression of innate antiviral response by severe acute respiratory syndrome coronavirus M protein is mediated through the first transmembrane domain. 24509444 0 41 theme transmembrane 130:142 arg1 domain 144:149 the first transmembrane domain 120:149 the first transmembrane domain 120:149 Suppression of innate antiviral response by severe acute respiratory syndrome coronavirus M protein is mediated through the first transmembrane domain. 24509444 3 42 theme located 597:603 arg1 TM1 592:594 TM1 592:594 TM1 592:594 In this study, we demonstrate that the IFN-antagonizing activity is specific to SARS coronavirus M protein and is mediated through its first transmembrane domain (TM1) located at the N terminus. 24509444 3 42 theme located 597:603 arg1 domain 584:589 its first transmembrane domain 560:589 its first transmembrane domain (TM1) located at the N terminus 560:621 In this study, we demonstrate that the IFN-antagonizing activity is specific to SARS coronavirus M protein and is mediated through its first transmembrane domain (TM1) located at the N terminus. 24509444 2 43 theme TRAF3-containing 403:418 arg1 complex 420:426 functional TRAF3-containing complex 392:426 functional TRAF3-containing complex 392:426 We have previously shown that severe acute respiratory syndrome (SARS) coronavirus M protein suppresses type I interferon (IFN) production by impeding the formation of functional TRAF3-containing complex. 24509444 0 44 theme acute 51:55 arg1 syndrome 69:76 severe acute respiratory syndrome 44:76 severe acute respiratory syndrome coronavirus M protein 44:98 Suppression of innate antiviral response by severe acute respiratory syndrome coronavirus M protein is mediated through the first transmembrane domain. 24509444 0 45 theme severe 44:49 arg1 syndrome 69:76 severe acute respiratory syndrome 44:76 severe acute respiratory syndrome coronavirus M protein 44:98 Suppression of innate antiviral response by severe acute respiratory syndrome coronavirus M protein is mediated through the first transmembrane domain. 24509444 2 46 theme functional 392:401 arg1 complex 420:426 functional TRAF3-containing complex 392:426 functional TRAF3-containing complex 392:426 We have previously shown that severe acute respiratory syndrome (SARS) coronavirus M protein suppresses type I interferon (IFN) production by impeding the formation of functional TRAF3-containing complex. 24509444 3 47 theme N 612:612 arg1 terminus 614:621 the N terminus 608:621 the N terminus 608:621 In this study, we demonstrate that the IFN-antagonizing activity is specific to SARS coronavirus M protein and is mediated through its first transmembrane domain (TM1) located at the N terminus. 24509444 2 48 theme syndrome 279:286 arg1 protein 309:315 severe acute respiratory syndrome (SARS) coronavirus M protein 254:315 severe acute respiratory syndrome (SARS) coronavirus M protein 254:315 We have previously shown that severe acute respiratory syndrome (SARS) coronavirus M protein suppresses type I interferon (IFN) production by impeding the formation of functional TRAF3-containing complex. 24509444 2 49 theme interferon 335:344 arg1 production 352:361 type I interferon (IFN) production 328:361 type I interferon (IFN) production 328:361 We have previously shown that severe acute respiratory syndrome (SARS) coronavirus M protein suppresses type I interferon (IFN) production by impeding the formation of functional TRAF3-containing complex. 24509444 5 50 theme coronavirus 734:744 arg1 protein 748:754 SARS coronavirus M protein 729:754 SARS coronavirus M protein 729:754 Whereas N-linked glycosylation of SARS coronavirus M protein has no influence on IFN antagonism, TM1 is indispensable for the suppression of IFN production. 24509444 2 51 theme respiratory 267:277 arg1 SARS 289:292 SARS 289:292 SARS 289:292 We have previously shown that severe acute respiratory syndrome (SARS) coronavirus M protein suppresses type I interferon (IFN) production by impeding the formation of functional TRAF3-containing complex. 24509444 2 51 theme respiratory 267:277 arg1 syndrome 279:286 severe acute respiratory syndrome 254:286 severe acute respiratory syndrome (SARS) coronavirus M protein 254:315 We have previously shown that severe acute respiratory syndrome (SARS) coronavirus M protein suppresses type I interferon (IFN) production by impeding the formation of functional TRAF3-containing complex. 24509444 8 52 theme response 1282:1289 arg1 suppression 1250:1260 suppression 1250:1260 suppression of innate antiviral response 1250:1289 Our work defines the molecular architecture of SARS coronavirus M protein required for suppression of innate antiviral response. 24509444 8 53 theme molecular 1184:1192 arg1 architecture 1194:1205 the molecular architecture 1180:1205 the molecular architecture of SARS coronavirus M protein required for suppression of innate antiviral response 1180:1289 Our work defines the molecular architecture of SARS coronavirus M protein required for suppression of innate antiviral response. 24509444 5 54 gly glycosylation 712:724 arg1 protein 748:754 SARS coronavirus M protein 729:754 SARS coronavirus M protein 729:754 Whereas N-linked glycosylation of SARS coronavirus M protein has no influence on IFN antagonism, TM1 is indispensable for the suppression of IFN production. 24509444 0 55 theme syndrome 69:76 arg1 protein 92:98 severe acute respiratory syndrome coronavirus M protein 44:98 severe acute respiratory syndrome coronavirus M protein 44:98 Suppression of innate antiviral response by severe acute respiratory syndrome coronavirus M protein is mediated through the first transmembrane domain. 24509444 5 56 theme IFN 836:838 arg1 production 840:849 IFN production 836:849 IFN production 836:849 Whereas N-linked glycosylation of SARS coronavirus M protein has no influence on IFN antagonism, TM1 is indispensable for the suppression of IFN production. 24509444 2 57 theme acute 261:265 arg1 SARS 289:292 SARS 289:292 SARS 289:292 We have previously shown that severe acute respiratory syndrome (SARS) coronavirus M protein suppresses type I interferon (IFN) production by impeding the formation of functional TRAF3-containing complex. 24509444 2 57 theme acute 261:265 arg1 syndrome 279:286 severe acute respiratory syndrome 254:286 severe acute respiratory syndrome (SARS) coronavirus M protein 254:315 We have previously shown that severe acute respiratory syndrome (SARS) coronavirus M protein suppresses type I interferon (IFN) production by impeding the formation of functional TRAF3-containing complex. 24509444 4 58 theme M 624:624 arg1 protein 626:632 M protein 624:632 M protein from human coronavirus HKU1 624:660 M protein from human coronavirus HKU1 does not inhibit IFN production. 24509444 3 59 theme M 526:526 arg1 protein 528:534 SARS coronavirus M protein 509:534 SARS coronavirus M protein 509:534 In this study, we demonstrate that the IFN-antagonizing activity is specific to SARS coronavirus M protein and is mediated through its first transmembrane domain (TM1) located at the N terminus. 24509444 8 60 theme innate 1265:1270 arg1 response 1282:1289 innate antiviral response 1265:1289 innate antiviral response 1265:1289 Our work defines the molecular architecture of SARS coronavirus M protein required for suppression of innate antiviral response. 24509444 6 61 theme IFN 999:1001 arg1 antagonism 1003:1012 IFN antagonism 999:1012 IFN antagonism 999:1012 TM1 targets SARS coronavirus M protein and heterologous proteins to the Golgi apparatus, yet Golgi localization is required but not sufficient for IFN antagonism. 24509444 0 62 theme respiratory 57:67 arg1 syndrome 69:76 severe acute respiratory syndrome 44:76 severe acute respiratory syndrome coronavirus M protein 44:98 Suppression of innate antiviral response by severe acute respiratory syndrome coronavirus M protein is mediated through the first transmembrane domain. 24509444 7 63 theme downstream 1141:1150 arg1 effectors 1152:1160 its downstream effectors 1137:1160 its downstream effectors 1137:1160 Mechanistically, TM1 is capable of binding with RIG-I, TRAF3, TBK1 and IKKε, and preventing the interaction of TRAF3 with its downstream effectors. 24509444 2 64 theme severe 254:259 arg1 SARS 289:292 SARS 289:292 SARS 289:292 We have previously shown that severe acute respiratory syndrome (SARS) coronavirus M protein suppresses type I interferon (IFN) production by impeding the formation of functional TRAF3-containing complex. 24509444 2 64 theme severe 254:259 arg1 syndrome 279:286 severe acute respiratory syndrome 254:286 severe acute respiratory syndrome (SARS) coronavirus M protein 254:315 We have previously shown that severe acute respiratory syndrome (SARS) coronavirus M protein suppresses type I interferon (IFN) production by impeding the formation of functional TRAF3-containing complex. 24509444 7 65 theme TRAF3 1126:1130 arg1 interaction 1111:1121 the interaction 1107:1121 the interaction of TRAF3 with its downstream effectors 1107:1160 Mechanistically, TM1 is capable of binding with RIG-I, TRAF3, TBK1 and IKKε, and preventing the interaction of TRAF3 with its downstream effectors. 24509444 5 66 theme SARS 729:732 arg1 coronavirus 734:744 SARS coronavirus 729:744 SARS coronavirus M protein 729:754 Whereas N-linked glycosylation of SARS coronavirus M protein has no influence on IFN antagonism, TM1 is indispensable for the suppression of IFN production. 26537754 12 0 theme Asn 1640:1642 arg1 effects 1586:1592 the effects 1582:1592 the effects of the Asn(679) loop residue and the N-glycan Asn(575) on transporter maturation 1582:1673 Further, double-mutant cycle analysis showed partial additivity of the effects of the Asn(679) loop residue and the N-glycan Asn(575) on transporter maturation, indicating that they may interact during system b(0,+) biogenesis. 26537754 9 1 theme maturation 1258:1267 arg1 rate 1238:1241 the maximum rate 1226:1241 the maximum rate of transporter maturation 1226:1267 Moreover, a transporter with only the N-glycan Asn(575) displayed similar maturation compared with wild-type, suggesting that this N-glycan was necessary and sufficient to achieve the maximum rate of transporter maturation. 26537754 4 2 theme plasma 622:627 arg1 membrane 629:636 the plasma membrane 618:636 the plasma membrane 618:636 It has been shown that upon assembly, b(0,+)AT prevents degradation and promotes folding of rBAT; then, rBAT traffics b(0,+)AT from the endoplasmic reticulum (ER) to the plasma membrane. 26537754 5 3 contain has 707:709 arg1 N-glycans 655:663 the N-glycans 651:663 the N-glycans 651:663 The role of the N-glycans of rBAT and of its C-terminal loop, which has no homology to any other sequence, in biogenesis of system b(0,+) is unknown. 26537754 5 3 contain has 707:709 arg2 homology 714:721 no homology 711:721 no homology to any other sequence 711:743 The role of the N-glycans of rBAT and of its C-terminal loop, which has no homology to any other sequence, in biogenesis of system b(0,+) is unknown. 26537754 4 4 theme rBAT 544:547 arg1 folding 533:539 folding 533:539 folding of rBAT 533:547 It has been shown that upon assembly, b(0,+)AT prevents degradation and promotes folding of rBAT; then, rBAT traffics b(0,+)AT from the endoplasmic reticulum (ER) to the plasma membrane. 26537754 12 5 theme residue 1615:1621 arg1 effects 1586:1592 the effects 1582:1592 the effects of the Asn(679) loop residue and the N-glycan Asn(575) on transporter maturation 1582:1673 Further, double-mutant cycle analysis showed partial additivity of the effects of the Asn(679) loop residue and the N-glycan Asn(575) on transporter maturation, indicating that they may interact during system b(0,+) biogenesis. 26537754 12 6 theme system 1717:1722 arg1 b 1724:1724 system b 1717:1724 system b 1717:1724 Further, double-mutant cycle analysis showed partial additivity of the effects of the Asn(679) loop residue and the N-glycan Asn(575) on transporter maturation, indicating that they may interact during system b(0,+) biogenesis. 26537754 8 7 theme N-glycan 903:910 arg1 575 916:918 575 916:918 575 916:918 Elimination of the N-glycan Asn(575), but not of the others, delayed transporter maturation, as measured by pulse chase experiments and endoglycosidase H assays. 26537754 8 7 theme N-glycan 903:910 arg1 Asn 912:914 the N-glycan Asn 899:914 the N-glycan Asn(575) 899:919 Elimination of the N-glycan Asn(575), but not of the others, delayed transporter maturation, as measured by pulse chase experiments and endoglycosidase H assays. 26537754 3 8 theme transporter 415:425 arg1 biogenesis 397:406 biogenesis 397:406 biogenesis of the transporter 397:425 rBAT mutations that impair biogenesis of the transporter cause type I cystinuria. 26537754 5 9 theme b 770:770 arg1 biogenesis 749:758 biogenesis 749:758 biogenesis of system b(0,+) 749:775 The role of the N-glycans of rBAT and of its C-terminal loop, which has no homology to any other sequence, in biogenesis of system b(0,+) is unknown. 26537754 10 10 theme transporter 1389:1399 arg1 degradation 1370:1380 degradation 1370:1380 degradation of the transporter 1370:1399 Deletion of the rBAT C-terminal disulfide loop (residues 673-685) prevented maturation and prompted degradation of the transporter. 26537754 9 11 theme N-glycan 1084:1091 arg1 575 1097:1099 575 1097:1099 575 1097:1099 Moreover, a transporter with only the N-glycan Asn(575) displayed similar maturation compared with wild-type, suggesting that this N-glycan was necessary and sufficient to achieve the maximum rate of transporter maturation. 26537754 9 11 theme N-glycan 1084:1091 arg1 Asn 1093:1095 only the N-glycan Asn 1075:1095 only the N-glycan Asn(575) 1075:1100 Moreover, a transporter with only the N-glycan Asn(575) displayed similar maturation compared with wild-type, suggesting that this N-glycan was necessary and sufficient to achieve the maximum rate of transporter maturation. 26537754 0 12 theme transporter 113:123 arg1 biogenesis 73:82 the biogenesis 69:82 the biogenesis of the cystinuria-associated transporter 69:123 The role of N-glycans and the C-terminal loop of the subunit rBAT in the biogenesis of the cystinuria-associated transporter. 26537754 1 13 from reabsorption 163:174 arg1 kidney 218:223 the kidney 214:223 the kidney 214:223 The transport system b(0,+) mediates reabsorption of dibasic amino acids and cystine in the kidney. 26537754 12 14 theme effects 1586:1592 arg1 additivity 1568:1577 partial additivity 1560:1577 partial additivity of the effects of the Asn(679) loop residue and the N-glycan Asn(575) on transporter maturation 1560:1673 Further, double-mutant cycle analysis showed partial additivity of the effects of the Asn(679) loop residue and the N-glycan Asn(575) on transporter maturation, indicating that they may interact during system b(0,+) biogenesis. 26537754 2 15 link disulfide-linked 247:262 arg1 carrier 287:293 the carrier 283:293 the carrier 283:293 It is made up of two disulfide-linked membrane subunits: the carrier, b(0,+)AT and the helper, rBAT (related to b(0,+) amino acid transporter). 26537754 2 15 link disulfide-linked 247:262 arg1 b 296:296 b(0,+)AT 296:303 b 296:296 It is made up of two disulfide-linked membrane subunits: the carrier, b(0,+)AT and the helper, rBAT (related to b(0,+) amino acid transporter). 26537754 2 15 link disulfide-linked 247:262 arg1 subunits 273:280 two disulfide-linked membrane subunits 243:280 two disulfide-linked membrane subunits: the carrier, b(0,+)AT and the helper, rBAT (related to b(0,+) amino acid transporter) 243:367 It is made up of two disulfide-linked membrane subunits: the carrier, b(0,+)AT and the helper, rBAT (related to b(0,+) amino acid transporter). 26537754 2 15 link disulfide-linked 247:262 arg1 AT 302:303 b(0,+)AT 296:303 AT 302:303 It is made up of two disulfide-linked membrane subunits: the carrier, b(0,+)AT and the helper, rBAT (related to b(0,+) amino acid transporter). 26537754 2 15 link disulfide-linked 247:262 arg1 helper 313:318 the helper 309:318 the helper 309:318 It is made up of two disulfide-linked membrane subunits: the carrier, b(0,+)AT and the helper, rBAT (related to b(0,+) amino acid transporter). 26537754 3 16 theme type I 433:438 arg1 cystinuria 440:449 type I cystinuria 433:449 type I cystinuria 433:449 rBAT mutations that impair biogenesis of the transporter cause type I cystinuria. 26537754 12 17 from maturation 1664:1673 arg1 additivity 1568:1577 partial additivity 1560:1577 partial additivity of the effects of the Asn(679) loop residue and the N-glycan Asn(575) on transporter maturation 1560:1673 Further, double-mutant cycle analysis showed partial additivity of the effects of the Asn(679) loop residue and the N-glycan Asn(575) on transporter maturation, indicating that they may interact during system b(0,+) biogenesis. 26537754 13 18 theme C-terminal 1816:1825 arg1 loop 1837:1840 the C-terminal disulfide loop 1812:1840 the C-terminal disulfide loop of rBAT 1812:1848 These data highlight the important role of the N-glycan Asn(575) and the C-terminal disulfide loop of rBAT in biogenesis of the rBAT-b(0,+)AT heterodimer. 26537754 9 19 theme similar 1112:1118 arg1 maturation 1120:1129 similar maturation 1112:1129 similar maturation 1112:1129 Moreover, a transporter with only the N-glycan Asn(575) displayed similar maturation compared with wild-type, suggesting that this N-glycan was necessary and sufficient to achieve the maximum rate of transporter maturation. 26537754 5 20 theme N-glycans 655:663 arg1 role 643:646 The role 639:646 The role of the N-glycans of rBAT and of its C-terminal loop, which has no homology to any other sequence, in biogenesis of system b(0,+) 639:775 The role of the N-glycans of rBAT and of its C-terminal loop, which has no homology to any other sequence, in biogenesis of system b(0,+) is unknown. 26537754 5 20 theme N-glycans 655:663 arg1 unknown 780:786 unknown 780:786 unknown 780:786 The role of the N-glycans of rBAT and of its C-terminal loop, which has no homology to any other sequence, in biogenesis of system b(0,+) is unknown. 26537754 2 21 theme amino 345:349 arg1 transporter 356:366 related to b(0,+) amino acid transporter 327:366 related to b(0,+) amino acid transporter 327:366 It is made up of two disulfide-linked membrane subunits: the carrier, b(0,+)AT and the helper, rBAT (related to b(0,+) amino acid transporter). 26537754 2 21 theme amino 345:349 arg1 rBAT 321:324 rBAT 321:324 rBAT (related to b(0,+) amino acid transporter) 321:367 It is made up of two disulfide-linked membrane subunits: the carrier, b(0,+)AT and the helper, rBAT (related to b(0,+) amino acid transporter). 26537754 8 22 theme others 937:942 arg1 Elimination 884:894 Elimination 884:894 Elimination of the N-glycan Asn(575), but not of the others, 884:943 Elimination of the N-glycan Asn(575), but not of the others, delayed transporter maturation, as measured by pulse chase experiments and endoglycosidase H assays. 26537754 1 23 theme transport 130:138 arg1 b 147:147 The transport system b 126:147 The transport system b(0,+) 126:152 The transport system b(0,+) mediates reabsorption of dibasic amino acids and cystine in the kidney. 26537754 11 24 theme Alanine-scanning 1402:1417 arg1 mutagenesis 1419:1429 Alanine-scanning mutagenesis 1402:1429 Alanine-scanning mutagenesis 1402:1429 Alanine-scanning mutagenesis uncovered loop residues important for stability and/or maturation of system b(0,+). 26537754 0 25 theme subunit 53:59 arg1 rBAT 61:64 the subunit rBAT 49:64 the subunit rBAT 49:64 The role of N-glycans and the C-terminal loop of the subunit rBAT in the biogenesis of the cystinuria-associated transporter. 26537754 12 26 theme cycle 1538:1542 arg1 analysis 1544:1551 double-mutant cycle analysis 1524:1551 double-mutant cycle analysis 1524:1551 Further, double-mutant cycle analysis showed partial additivity of the effects of the Asn(679) loop residue and the N-glycan Asn(575) on transporter maturation, indicating that they may interact during system b(0,+) biogenesis. 26537754 8 27 theme pulse 992:996 arg1 experiments 1004:1014 pulse chase experiments 992:1014 pulse chase experiments 992:1014 Elimination of the N-glycan Asn(575), but not of the others, delayed transporter maturation, as measured by pulse chase experiments and endoglycosidase H assays. 26537754 5 28 theme loop 695:698 arg1 N-glycans 655:663 the N-glycans 651:663 the N-glycans 651:663 The role of the N-glycans of rBAT and of its C-terminal loop, which has no homology to any other sequence, in biogenesis of system b(0,+) is unknown. 26537754 13 29 theme loop 1837:1840 arg1 role 1778:1781 the important role 1764:1781 the important role of the N-glycan Asn(575) and the C-terminal disulfide loop of rBAT in biogenesis of the rBAT-b(0,+)AT heterodimer 1764:1895 These data highlight the important role of the N-glycan Asn(575) and the C-terminal disulfide loop of rBAT in biogenesis of the rBAT-b(0,+)AT heterodimer. 26537754 4 30 from reticulum 600:608 arg1 b 570:570 b(0,+)AT 570:577 b 570:570 It has been shown that upon assembly, b(0,+)AT prevents degradation and promotes folding of rBAT; then, rBAT traffics b(0,+)AT from the endoplasmic reticulum (ER) to the plasma membrane. 26537754 2 31 theme membrane 264:271 arg1 carrier 287:293 the carrier 283:293 the carrier 283:293 It is made up of two disulfide-linked membrane subunits: the carrier, b(0,+)AT and the helper, rBAT (related to b(0,+) amino acid transporter). 26537754 2 31 theme membrane 264:271 arg1 b 296:296 b(0,+)AT 296:303 b 296:296 It is made up of two disulfide-linked membrane subunits: the carrier, b(0,+)AT and the helper, rBAT (related to b(0,+) amino acid transporter). 26537754 2 31 theme membrane 264:271 arg1 subunits 273:280 two disulfide-linked membrane subunits 243:280 two disulfide-linked membrane subunits: the carrier, b(0,+)AT and the helper, rBAT (related to b(0,+) amino acid transporter) 243:367 It is made up of two disulfide-linked membrane subunits: the carrier, b(0,+)AT and the helper, rBAT (related to b(0,+) amino acid transporter). 26537754 2 31 theme membrane 264:271 arg1 AT 302:303 b(0,+)AT 296:303 AT 302:303 It is made up of two disulfide-linked membrane subunits: the carrier, b(0,+)AT and the helper, rBAT (related to b(0,+) amino acid transporter). 26537754 2 31 theme membrane 264:271 arg1 helper 313:318 the helper 309:318 the helper 309:318 It is made up of two disulfide-linked membrane subunits: the carrier, b(0,+)AT and the helper, rBAT (related to b(0,+) amino acid transporter). 26537754 2 32 theme related 327:333 arg1 transporter 356:366 related to b(0,+) amino acid transporter 327:366 related to b(0,+) amino acid transporter 327:366 It is made up of two disulfide-linked membrane subunits: the carrier, b(0,+)AT and the helper, rBAT (related to b(0,+) amino acid transporter). 26537754 2 32 theme related 327:333 arg1 rBAT 321:324 rBAT 321:324 rBAT (related to b(0,+) amino acid transporter) 321:367 It is made up of two disulfide-linked membrane subunits: the carrier, b(0,+)AT and the helper, rBAT (related to b(0,+) amino acid transporter). 26537754 2 33 dep subunits 273:280 arg1 subunits 273:280 two disulfide-linked membrane subunits 243:280 two disulfide-linked membrane subunits: the carrier, b(0,+)AT and the helper, rBAT (related to b(0,+) amino acid transporter) 243:367 It is made up of two disulfide-linked membrane subunits: the carrier, b(0,+)AT and the helper, rBAT (related to b(0,+) amino acid transporter). 26537754 2 33 dep subunits 273:280 arg1 b 296:296 b(0,+)AT 296:303 b 296:296 It is made up of two disulfide-linked membrane subunits: the carrier, b(0,+)AT and the helper, rBAT (related to b(0,+) amino acid transporter). 26537754 2 33 dep subunits 273:280 arg1 rBAT 321:324 rBAT 321:324 rBAT (related to b(0,+) amino acid transporter) 321:367 It is made up of two disulfide-linked membrane subunits: the carrier, b(0,+)AT and the helper, rBAT (related to b(0,+) amino acid transporter). 26537754 2 33 dep subunits 273:280 arg1 carrier 287:293 the carrier 283:293 the carrier 283:293 It is made up of two disulfide-linked membrane subunits: the carrier, b(0,+)AT and the helper, rBAT (related to b(0,+) amino acid transporter). 26537754 2 33 dep subunits 273:280 arg1 helper 313:318 the helper 309:318 the helper 309:318 It is made up of two disulfide-linked membrane subunits: the carrier, b(0,+)AT and the helper, rBAT (related to b(0,+) amino acid transporter). 26537754 8 34 theme chase 998:1002 arg1 experiments 1004:1014 pulse chase experiments 992:1014 pulse chase experiments 992:1014 Elimination of the N-glycan Asn(575), but not of the others, delayed transporter maturation, as measured by pulse chase experiments and endoglycosidase H assays. 26537754 10 35 theme disulfide 1302:1310 arg1 residues 1318:1325 residues 673-685 1318:1333 residues 673-685 1318:1333 Deletion of the rBAT C-terminal disulfide loop (residues 673-685) prevented maturation and prompted degradation of the transporter. 26537754 10 35 theme disulfide 1302:1310 arg1 loop 1312:1315 the rBAT C-terminal disulfide loop 1282:1315 the rBAT C-terminal disulfide loop (residues 673-685) 1282:1334 Deletion of the rBAT C-terminal disulfide loop (residues 673-685) prevented maturation and prompted degradation of the transporter. 26537754 13 36 theme N-glycan 1790:1797 arg1 575 1803:1805 575 1803:1805 575 1803:1805 These data highlight the important role of the N-glycan Asn(575) and the C-terminal disulfide loop of rBAT in biogenesis of the rBAT-b(0,+)AT heterodimer. 26537754 13 36 theme N-glycan 1790:1797 arg1 Asn 1799:1801 the N-glycan Asn 1786:1801 the N-glycan Asn(575) 1786:1806 These data highlight the important role of the N-glycan Asn(575) and the C-terminal disulfide loop of rBAT in biogenesis of the rBAT-b(0,+)AT heterodimer. 26537754 10 37 theme rBAT 1286:1289 arg1 residues 1318:1325 residues 673-685 1318:1333 residues 673-685 1318:1333 Deletion of the rBAT C-terminal disulfide loop (residues 673-685) prevented maturation and prompted degradation of the transporter. 26537754 10 37 theme rBAT 1286:1289 arg1 loop 1312:1315 the rBAT C-terminal disulfide loop 1282:1315 the rBAT C-terminal disulfide loop (residues 673-685) 1282:1334 Deletion of the rBAT C-terminal disulfide loop (residues 673-685) prevented maturation and prompted degradation of the transporter. 26537754 5 38 theme other 730:734 arg1 sequence 736:743 any other sequence 726:743 any other sequence 726:743 The role of the N-glycans of rBAT and of its C-terminal loop, which has no homology to any other sequence, in biogenesis of system b(0,+) is unknown. 26537754 8 39 theme H 1036:1036 arg1 assays 1038:1043 endoglycosidase H assays 1020:1043 endoglycosidase H assays 1020:1043 Elimination of the N-glycan Asn(575), but not of the others, delayed transporter maturation, as measured by pulse chase experiments and endoglycosidase H assays. 26537754 11 40 theme b 1507:1507 arg1 stability 1469:1477 stability 1469:1477 stability 1469:1477 Alanine-scanning mutagenesis uncovered loop residues important for stability and/or maturation of system b(0,+). 26537754 0 41 theme C-terminal 30:39 arg1 loop 41:44 the C-terminal loop 26:44 the C-terminal loop of the subunit rBAT in the biogenesis of the cystinuria-associated transporter 26:123 The role of N-glycans and the C-terminal loop of the subunit rBAT in the biogenesis of the cystinuria-associated transporter. 26537754 13 42 theme important 1768:1776 arg1 role 1778:1781 the important role 1764:1781 the important role of the N-glycan Asn(575) and the C-terminal disulfide loop of rBAT in biogenesis of the rBAT-b(0,+)AT heterodimer 1764:1895 These data highlight the important role of the N-glycan Asn(575) and the C-terminal disulfide loop of rBAT in biogenesis of the rBAT-b(0,+)AT heterodimer. 26537754 12 43 from effects 1586:1592 arg1 maturation 1664:1673 transporter maturation 1652:1673 transporter maturation 1652:1673 Further, double-mutant cycle analysis showed partial additivity of the effects of the Asn(679) loop residue and the N-glycan Asn(575) on transporter maturation, indicating that they may interact during system b(0,+) biogenesis. 26537754 13 44 theme heterodimer 1885:1895 arg1 biogenesis 1853:1862 biogenesis 1853:1862 biogenesis of the rBAT-b(0,+)AT heterodimer 1853:1895 These data highlight the important role of the N-glycan Asn(575) and the C-terminal disulfide loop of rBAT in biogenesis of the rBAT-b(0,+)AT heterodimer. 26537754 1 45 theme dibasic 179:185 arg1 acids 193:197 dibasic amino acids 179:197 dibasic amino acids 179:197 The transport system b(0,+) mediates reabsorption of dibasic amino acids and cystine in the kidney. 26537754 1 46 theme acids 193:197 arg1 reabsorption 163:174 reabsorption 163:174 reabsorption of dibasic amino acids 163:197 The transport system b(0,+) mediates reabsorption of dibasic amino acids and cystine in the kidney. 26537754 1 46 theme acids 193:197 arg1 cystine 203:209 cystine 203:209 cystine in the kidney 203:223 The transport system b(0,+) mediates reabsorption of dibasic amino acids and cystine in the kidney. 26537754 9 47 theme transporter 1246:1256 arg1 maturation 1258:1267 transporter maturation 1246:1267 transporter maturation 1246:1267 Moreover, a transporter with only the N-glycan Asn(575) displayed similar maturation compared with wild-type, suggesting that this N-glycan was necessary and sufficient to achieve the maximum rate of transporter maturation. 26537754 12 48 theme N-glycan 1631:1638 arg1 575 1644:1646 575 1644:1646 575 1644:1646 Further, double-mutant cycle analysis showed partial additivity of the effects of the Asn(679) loop residue and the N-glycan Asn(575) on transporter maturation, indicating that they may interact during system b(0,+) biogenesis. 26537754 12 48 theme N-glycan 1631:1638 arg1 Asn 1640:1642 the N-glycan Asn 1627:1642 the N-glycan Asn(575) 1627:1647 Further, double-mutant cycle analysis showed partial additivity of the effects of the Asn(679) loop residue and the N-glycan Asn(575) on transporter maturation, indicating that they may interact during system b(0,+) biogenesis. 26537754 3 49 theme rBAT 370:373 arg1 mutations 375:383 rBAT mutations 370:383 rBAT mutations that impair biogenesis of the transporter 370:425 rBAT mutations that impair biogenesis of the transporter cause type I cystinuria. 26537754 12 50 theme loop 1610:1613 arg1 residue 1615:1621 the Asn(679) loop residue 1597:1621 the Asn(679) loop residue 1597:1621 Further, double-mutant cycle analysis showed partial additivity of the effects of the Asn(679) loop residue and the N-glycan Asn(575) on transporter maturation, indicating that they may interact during system b(0,+) biogenesis. 26537754 4 51 theme endoplasmic 588:598 arg1 ER 611:612 ER 611:612 ER 611:612 It has been shown that upon assembly, b(0,+)AT prevents degradation and promotes folding of rBAT; then, rBAT traffics b(0,+)AT from the endoplasmic reticulum (ER) to the plasma membrane. 26537754 4 51 theme endoplasmic 588:598 arg1 reticulum 600:608 the endoplasmic reticulum 584:608 the endoplasmic reticulum (ER) 584:613 It has been shown that upon assembly, b(0,+)AT prevents degradation and promotes folding of rBAT; then, rBAT traffics b(0,+)AT from the endoplasmic reticulum (ER) to the plasma membrane. 26537754 2 52 theme disulfide-linked 247:262 arg1 carrier 287:293 the carrier 283:293 the carrier 283:293 It is made up of two disulfide-linked membrane subunits: the carrier, b(0,+)AT and the helper, rBAT (related to b(0,+) amino acid transporter). 26537754 2 52 theme disulfide-linked 247:262 arg1 b 296:296 b(0,+)AT 296:303 b 296:296 It is made up of two disulfide-linked membrane subunits: the carrier, b(0,+)AT and the helper, rBAT (related to b(0,+) amino acid transporter). 26537754 2 52 theme disulfide-linked 247:262 arg1 subunits 273:280 two disulfide-linked membrane subunits 243:280 two disulfide-linked membrane subunits: the carrier, b(0,+)AT and the helper, rBAT (related to b(0,+) amino acid transporter) 243:367 It is made up of two disulfide-linked membrane subunits: the carrier, b(0,+)AT and the helper, rBAT (related to b(0,+) amino acid transporter). 26537754 2 52 theme disulfide-linked 247:262 arg1 AT 302:303 b(0,+)AT 296:303 AT 302:303 It is made up of two disulfide-linked membrane subunits: the carrier, b(0,+)AT and the helper, rBAT (related to b(0,+) amino acid transporter). 26537754 2 52 theme disulfide-linked 247:262 arg1 helper 313:318 the helper 309:318 the helper 309:318 It is made up of two disulfide-linked membrane subunits: the carrier, b(0,+)AT and the helper, rBAT (related to b(0,+) amino acid transporter). 26537754 13 53 theme rBAT-b 1871:1876 arg1 biogenesis 1853:1862 biogenesis 1853:1862 biogenesis of the rBAT-b(0,+)AT heterodimer 1853:1895 These data highlight the important role of the N-glycan Asn(575) and the C-terminal disulfide loop of rBAT in biogenesis of the rBAT-b(0,+)AT heterodimer. 26537754 11 54 theme important 1455:1463 arg1 residues 1446:1453 loop residues 1441:1453 loop residues important for stability and/or maturation of system b(0,+) 1441:1512 Alanine-scanning mutagenesis uncovered loop residues important for stability and/or maturation of system b(0,+). 26537754 0 55 theme cystinuria-associated 91:111 arg1 transporter 113:123 the cystinuria-associated transporter 87:123 the cystinuria-associated transporter 87:123 The role of N-glycans and the C-terminal loop of the subunit rBAT in the biogenesis of the cystinuria-associated transporter. 26537754 12 56 theme Asn 1601:1603 arg1 residue 1615:1621 the Asn(679) loop residue 1597:1621 the Asn(679) loop residue 1597:1621 Further, double-mutant cycle analysis showed partial additivity of the effects of the Asn(679) loop residue and the N-glycan Asn(575) on transporter maturation, indicating that they may interact during system b(0,+) biogenesis. 26537754 8 57 theme Asn 912:914 arg1 Elimination 884:894 Elimination 884:894 Elimination of the N-glycan Asn(575), but not of the others, 884:943 Elimination of the N-glycan Asn(575), but not of the others, delayed transporter maturation, as measured by pulse chase experiments and endoglycosidase H assays. 26537754 11 58 theme loop 1441:1444 arg1 residues 1446:1453 loop residues 1441:1453 loop residues important for stability and/or maturation of system b(0,+) 1441:1512 Alanine-scanning mutagenesis uncovered loop residues important for stability and/or maturation of system b(0,+). 26537754 1 59 from cystine 203:209 arg1 kidney 218:223 the kidney 214:223 the kidney 214:223 The transport system b(0,+) mediates reabsorption of dibasic amino acids and cystine in the kidney. 26537754 12 60 theme transporter 1652:1662 arg1 maturation 1664:1673 transporter maturation 1652:1673 transporter maturation 1652:1673 Further, double-mutant cycle analysis showed partial additivity of the effects of the Asn(679) loop residue and the N-glycan Asn(575) on transporter maturation, indicating that they may interact during system b(0,+) biogenesis. 26537754 13 61 theme disulfide 1827:1835 arg1 loop 1837:1840 the C-terminal disulfide loop 1812:1840 the C-terminal disulfide loop of rBAT 1812:1848 These data highlight the important role of the N-glycan Asn(575) and the C-terminal disulfide loop of rBAT in biogenesis of the rBAT-b(0,+)AT heterodimer. 26537754 7 62 theme rBAT 878:881 arg1 N-glycans 865:873 the five N-glycans 856:873 the five N-glycans of rBAT 856:881 We first identified the five N-glycans of rBAT. 26537754 5 63 theme system 763:768 arg1 b 770:770 system b 763:770 system b(0,+) 763:775 The role of the N-glycans of rBAT and of its C-terminal loop, which has no homology to any other sequence, in biogenesis of system b(0,+) is unknown. 26537754 0 64 theme rBAT 61:64 arg1 role 4:7 The role 0:7 The role of N-glycans 0:20 The role of N-glycans and the C-terminal loop of the subunit rBAT in the biogenesis of the cystinuria-associated transporter. 26537754 0 64 theme rBAT 61:64 arg1 loop 41:44 the C-terminal loop 26:44 the C-terminal loop of the subunit rBAT in the biogenesis of the cystinuria-associated transporter 26:123 The role of N-glycans and the C-terminal loop of the subunit rBAT in the biogenesis of the cystinuria-associated transporter. 26537754 2 65 dep b 338:338 arg1 0 340:340 0 340:340 0 340:340 It is made up of two disulfide-linked membrane subunits: the carrier, b(0,+)AT and the helper, rBAT (related to b(0,+) amino acid transporter). 26537754 1 66 theme system 140:145 arg1 b 147:147 The transport system b 126:147 The transport system b(0,+) 126:152 The transport system b(0,+) mediates reabsorption of dibasic amino acids and cystine in the kidney. 26537754 0 67 from role 4:7 arg1 biogenesis 73:82 the biogenesis 69:82 the biogenesis of the cystinuria-associated transporter 69:123 The role of N-glycans and the C-terminal loop of the subunit rBAT in the biogenesis of the cystinuria-associated transporter. 26537754 13 68 from role 1778:1781 arg1 biogenesis 1853:1862 biogenesis 1853:1862 biogenesis of the rBAT-b(0,+)AT heterodimer 1853:1895 These data highlight the important role of the N-glycan Asn(575) and the C-terminal disulfide loop of rBAT in biogenesis of the rBAT-b(0,+)AT heterodimer. 26537754 12 69 theme partial 1560:1566 arg1 additivity 1568:1577 partial additivity 1560:1577 partial additivity of the effects of the Asn(679) loop residue and the N-glycan Asn(575) on transporter maturation 1560:1673 Further, double-mutant cycle analysis showed partial additivity of the effects of the Asn(679) loop residue and the N-glycan Asn(575) on transporter maturation, indicating that they may interact during system b(0,+) biogenesis. 26537754 5 70 from role 643:646 arg1 biogenesis 749:758 biogenesis 749:758 biogenesis of system b(0,+) 749:775 The role of the N-glycans of rBAT and of its C-terminal loop, which has no homology to any other sequence, in biogenesis of system b(0,+) is unknown. 26537754 5 71 theme C-terminal 684:693 arg1 loop 695:698 its C-terminal loop 680:698 its C-terminal loop 680:698 The role of the N-glycans of rBAT and of its C-terminal loop, which has no homology to any other sequence, in biogenesis of system b(0,+) is unknown. 26537754 0 72 from loop 41:44 arg1 biogenesis 73:82 the biogenesis 69:82 the biogenesis of the cystinuria-associated transporter 69:123 The role of N-glycans and the C-terminal loop of the subunit rBAT in the biogenesis of the cystinuria-associated transporter. 26537754 8 73 theme transporter 953:963 arg1 maturation 965:974 transporter maturation 953:974 transporter maturation 953:974 Elimination of the N-glycan Asn(575), but not of the others, delayed transporter maturation, as measured by pulse chase experiments and endoglycosidase H assays. 26537754 10 74 theme loop 1312:1315 arg1 Deletion 1270:1277 Deletion 1270:1277 Deletion of the rBAT C-terminal disulfide loop (residues 673-685) 1270:1334 Deletion of the rBAT C-terminal disulfide loop (residues 673-685) prevented maturation and prompted degradation of the transporter. 26537754 13 75 theme rBAT 1845:1848 arg1 loop 1837:1840 the C-terminal disulfide loop 1812:1840 the C-terminal disulfide loop of rBAT 1812:1848 These data highlight the important role of the N-glycan Asn(575) and the C-terminal disulfide loop of rBAT in biogenesis of the rBAT-b(0,+)AT heterodimer. 26537754 13 75 theme rBAT 1845:1848 arg1 575 1803:1805 575 1803:1805 575 1803:1805 These data highlight the important role of the N-glycan Asn(575) and the C-terminal disulfide loop of rBAT in biogenesis of the rBAT-b(0,+)AT heterodimer. 26537754 13 75 theme rBAT 1845:1848 arg1 Asn 1799:1801 the N-glycan Asn 1786:1801 the N-glycan Asn(575) 1786:1806 These data highlight the important role of the N-glycan Asn(575) and the C-terminal disulfide loop of rBAT in biogenesis of the rBAT-b(0,+)AT heterodimer. 26537754 11 76 dep b 1507:1507 arg1 0 1509:1509 0 1509:1509 0 1509:1509 Alanine-scanning mutagenesis uncovered loop residues important for stability and/or maturation of system b(0,+). 26537754 2 77 theme acid 351:354 arg1 transporter 356:366 related to b(0,+) amino acid transporter 327:366 related to b(0,+) amino acid transporter 327:366 It is made up of two disulfide-linked membrane subunits: the carrier, b(0,+)AT and the helper, rBAT (related to b(0,+) amino acid transporter). 26537754 2 77 theme acid 351:354 arg1 rBAT 321:324 rBAT 321:324 rBAT (related to b(0,+) amino acid transporter) 321:367 It is made up of two disulfide-linked membrane subunits: the carrier, b(0,+)AT and the helper, rBAT (related to b(0,+) amino acid transporter). 26537754 12 78 theme double-mutant 1524:1536 arg1 analysis 1544:1551 double-mutant cycle analysis 1524:1551 double-mutant cycle analysis 1524:1551 Further, double-mutant cycle analysis showed partial additivity of the effects of the Asn(679) loop residue and the N-glycan Asn(575) on transporter maturation, indicating that they may interact during system b(0,+) biogenesis. 26537754 5 79 theme rBAT 668:671 arg1 N-glycans 655:663 the N-glycans 651:663 the N-glycans 651:663 The role of the N-glycans of rBAT and of its C-terminal loop, which has no homology to any other sequence, in biogenesis of system b(0,+) is unknown. 26537754 1 80 dep b 147:147 arg1 0 149:149 0 149:149 0 149:149 The transport system b(0,+) mediates reabsorption of dibasic amino acids and cystine in the kidney. 26537754 0 81 theme N-glycans 12:20 arg1 role 4:7 The role 0:7 The role of N-glycans 0:20 The role of N-glycans and the C-terminal loop of the subunit rBAT in the biogenesis of the cystinuria-associated transporter. 26537754 0 81 theme N-glycans 12:20 arg1 loop 41:44 the C-terminal loop 26:44 the C-terminal loop of the subunit rBAT in the biogenesis of the cystinuria-associated transporter 26:123 The role of N-glycans and the C-terminal loop of the subunit rBAT in the biogenesis of the cystinuria-associated transporter. 26537754 10 82 dep residues 1318:1325 arg1 673-685 1327:1333 673-685 1327:1333 673-685 1327:1333 Deletion of the rBAT C-terminal disulfide loop (residues 673-685) prevented maturation and prompted degradation of the transporter. 26537754 10 83 theme C-terminal 1291:1300 arg1 residues 1318:1325 residues 673-685 1318:1333 residues 673-685 1318:1333 Deletion of the rBAT C-terminal disulfide loop (residues 673-685) prevented maturation and prompted degradation of the transporter. 26537754 10 83 theme C-terminal 1291:1300 arg1 loop 1312:1315 the rBAT C-terminal disulfide loop 1282:1315 the rBAT C-terminal disulfide loop (residues 673-685) 1282:1334 Deletion of the rBAT C-terminal disulfide loop (residues 673-685) prevented maturation and prompted degradation of the transporter. 26537754 13 84 theme Asn 1799:1801 arg1 role 1778:1781 the important role 1764:1781 the important role of the N-glycan Asn(575) and the C-terminal disulfide loop of rBAT in biogenesis of the rBAT-b(0,+)AT heterodimer 1764:1895 These data highlight the important role of the N-glycan Asn(575) and the C-terminal disulfide loop of rBAT in biogenesis of the rBAT-b(0,+)AT heterodimer. 26537754 13 85 theme AT 1882:1883 arg1 heterodimer 1885:1895 rBAT-b(0,+)AT heterodimer 1871:1895 heterodimer 1885:1895 These data highlight the important role of the N-glycan Asn(575) and the C-terminal disulfide loop of rBAT in biogenesis of the rBAT-b(0,+)AT heterodimer. 26537754 6 86 theme present 796:802 arg1 study 804:808 the present study 792:808 the present study 792:808 In the present study, we studied these points. 26537754 8 87 theme endoglycosidase 1020:1034 arg1 H 1036:1036 endoglycosidase H 1020:1036 endoglycosidase H assays 1020:1043 Elimination of the N-glycan Asn(575), but not of the others, delayed transporter maturation, as measured by pulse chase experiments and endoglycosidase H assays. 26537754 9 88 theme maximum 1230:1236 arg1 rate 1238:1241 the maximum rate 1226:1241 the maximum rate of transporter maturation 1226:1267 Moreover, a transporter with only the N-glycan Asn(575) displayed similar maturation compared with wild-type, suggesting that this N-glycan was necessary and sufficient to achieve the maximum rate of transporter maturation. 26537754 9 89 with transporter 1058:1068 arg1 575 1097:1099 575 1097:1099 575 1097:1099 Moreover, a transporter with only the N-glycan Asn(575) displayed similar maturation compared with wild-type, suggesting that this N-glycan was necessary and sufficient to achieve the maximum rate of transporter maturation. 26537754 9 89 with transporter 1058:1068 arg1 Asn 1093:1095 only the N-glycan Asn 1075:1095 only the N-glycan Asn(575) 1075:1100 Moreover, a transporter with only the N-glycan Asn(575) displayed similar maturation compared with wild-type, suggesting that this N-glycan was necessary and sufficient to achieve the maximum rate of transporter maturation. 26537754 11 90 theme system 1500:1505 arg1 b 1507:1507 system b 1500:1507 system b(0,+) 1500:1512 Alanine-scanning mutagenesis uncovered loop residues important for stability and/or maturation of system b(0,+). 26537754 1 91 theme amino 187:191 arg1 acids 193:197 dibasic amino acids 179:197 dibasic amino acids 179:197 The transport system b(0,+) mediates reabsorption of dibasic amino acids and cystine in the kidney. 26537754 12 92 from additivity 1568:1577 arg1 maturation 1664:1673 transporter maturation 1652:1673 transporter maturation 1652:1673 Further, double-mutant cycle analysis showed partial additivity of the effects of the Asn(679) loop residue and the N-glycan Asn(575) on transporter maturation, indicating that they may interact during system b(0,+) biogenesis. 26537754 5 93 dep b 770:770 arg1 0 772:772 0 772:772 0 772:772 The role of the N-glycans of rBAT and of its C-terminal loop, which has no homology to any other sequence, in biogenesis of system b(0,+) is unknown. 29126476 8 0 theme classification 1158:1171 arg1 percentages 1135:1145 The percentages 1131:1145 The percentages of correct classification of the models 1131:1185 The percentages of correct classification of the models reached 95.45% for the chronic kidney disease dataset and 85.42% for the anti-platelet drug response dataset. 29126476 6 1 theme confirmed 926:934 arg1 structure 936:944 confirmed structure 926:944 confirmed structure for most glycans 926:961 37 N-glycan peaks were observed from separation results, with confirmed structure for most glycans. 29126476 3 2 link N-linked 487:494 arg1 glycans 496:502 the major N-linked glycans 477:502 the major N-linked glycans (N-glycans) found in human plasma 477:536 This work demonstrates the use of a high-throughput GlycanAssure™ sample preparation technology and multi-capillary DNA analyzer for the analysis of the major N-linked glycans (N-glycans) found in human plasma. 29126476 3 2 link N-linked 487:494 arg1 N-glycans 505:513 N-glycans 505:513 N-glycans 505:513 This work demonstrates the use of a high-throughput GlycanAssure™ sample preparation technology and multi-capillary DNA analyzer for the analysis of the major N-linked glycans (N-glycans) found in human plasma. 29126476 9 3 theme high-throughput 1387:1401 arg1 platform 1403:1410 this high-throughput platform 1382:1410 this high-throughput platform 1382:1410 Given that blood N-glycan profiles had been shown to reflect certain disease states, this high-throughput platform could potentially be used for the simultaneous screening of multiple glycan biomarkers, with as little as one drop of blood sample. 29126476 1 4 theme compounds 160:168 arg1 majority 140:147 the majority 136:147 the majority of organic compounds found in nature 136:184 Carbohydrates form the majority of organic compounds found in nature and their presence on proteins influences many important bioactivities. 29126476 4 5 from controls 703:710 arg1 response 715:722 response 715:722 response to an antiplatelet drug from hypo-responders 715:767 The application involves two biomarker studies: (1) in profiling patients with chronic kidney disease and (2) in differentiating heart disease patients with normal controls in response to an antiplatelet drug from hypo-responders. 29126476 4 6 theme profiling 594:602 arg1 patients 604:611 profiling patients 594:611 profiling patients with chronic kidney disease 594:639 The application involves two biomarker studies: (1) in profiling patients with chronic kidney disease and (2) in differentiating heart disease patients with normal controls in response to an antiplatelet drug from hypo-responders. 29126476 0 7 theme multivariate 70:81 arg1 analysis 83:90 multivariate analysis 70:90 multivariate analysis for biomarker discovery 70:114 High throughput human plasma N-glycan analysis using DNA analyzer and multivariate analysis for biomarker discovery. 29126476 8 8 theme disease 1225:1231 arg1 dataset 1233:1239 the chronic kidney disease dataset 1206:1239 the chronic kidney disease dataset 1206:1239 The percentages of correct classification of the models reached 95.45% for the chronic kidney disease dataset and 85.42% for the anti-platelet drug response dataset. 29126476 9 9 theme blood 1530:1534 arg1 sample 1536:1541 blood sample 1530:1541 blood sample 1530:1541 Given that blood N-glycan profiles had been shown to reflect certain disease states, this high-throughput platform could potentially be used for the simultaneous screening of multiple glycan biomarkers, with as little as one drop of blood sample. 29126476 0 10 theme biomarker 96:104 arg1 discovery 106:114 biomarker discovery 96:114 biomarker discovery 96:114 High throughput human plasma N-glycan analysis using DNA analyzer and multivariate analysis for biomarker discovery. 29126476 4 11 with patients 604:611 arg1 controls 703:710 normal controls 696:710 normal controls in response to an antiplatelet drug from hypo-responders 696:767 The application involves two biomarker studies: (1) in profiling patients with chronic kidney disease and (2) in differentiating heart disease patients with normal controls in response to an antiplatelet drug from hypo-responders. 29126476 4 11 with patients 604:611 arg1 disease 633:639 chronic kidney disease 618:639 chronic kidney disease 618:639 The application involves two biomarker studies: (1) in profiling patients with chronic kidney disease and (2) in differentiating heart disease patients with normal controls in response to an antiplatelet drug from hypo-responders. 29126476 7 12 theme patient 1115:1121 arg1 groups 1123:1128 the patient groups 1111:1128 the patient groups 1111:1128 Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to build models to differentiate the patient groups. 29126476 9 13 theme simultaneous 1446:1457 arg1 screening 1459:1467 the simultaneous screening 1442:1467 the simultaneous screening of multiple glycan biomarkers 1442:1497 Given that blood N-glycan profiles had been shown to reflect certain disease states, this high-throughput platform could potentially be used for the simultaneous screening of multiple glycan biomarkers, with as little as one drop of blood sample. 29126476 2 14 theme clinical 305:312 arg1 applications 314:325 clinical applications 305:325 clinical applications 305:325 Therefore, glycan profiling shows potential in clinical applications. 29126476 7 15 used used 1073:1076 arg2 analysis 1049:1056 orthogonal partial least squares discriminant analysis 1003:1056 orthogonal partial least squares discriminant analysis (OPLS-DA) 1003:1066 Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to build models to differentiate the patient groups. 29126476 7 15 used used 1073:1076 arg2 analysis 984:991 Principal component analysis 964:991 Principal component analysis (PCA) 964:997 Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to build models to differentiate the patient groups. 29126476 7 15 used used 1073:1076 arg2 OPLS-DA 1059:1065 OPLS-DA 1059:1065 OPLS-DA 1059:1065 Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to build models to differentiate the patient groups. 29126476 7 15 used used 1073:1076 arg2 PCA 994:996 PCA 994:996 PCA 994:996 Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to build models to differentiate the patient groups. 29126476 3 16 theme sample 394:399 arg1 preparation 401:411 a high-throughput GlycanAssure™ sample preparation 362:411 a high-throughput GlycanAssure™ sample preparation technology 362:422 This work demonstrates the use of a high-throughput GlycanAssure™ sample preparation technology and multi-capillary DNA analyzer for the analysis of the major N-linked glycans (N-glycans) found in human plasma. 29126476 9 17 theme blood 1308:1312 arg1 profiles 1323:1330 blood N-glycan profiles 1308:1330 blood N-glycan profiles 1308:1330 Given that blood N-glycan profiles had been shown to reflect certain disease states, this high-throughput platform could potentially be used for the simultaneous screening of multiple glycan biomarkers, with as little as one drop of blood sample. 29126476 7 18 theme Principal 964:972 arg1 PCA 994:996 PCA 994:996 PCA 994:996 Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to build models to differentiate the patient groups. 29126476 7 18 theme Principal 964:972 arg1 analysis 984:991 Principal component analysis 964:991 Principal component analysis (PCA) 964:997 Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to build models to differentiate the patient groups. 29126476 9 19 theme multiple 1472:1479 arg1 biomarkers 1488:1497 multiple glycan biomarkers 1472:1497 multiple glycan biomarkers 1472:1497 Given that blood N-glycan profiles had been shown to reflect certain disease states, this high-throughput platform could potentially be used for the simultaneous screening of multiple glycan biomarkers, with as little as one drop of blood sample. 29126476 6 20 theme separation 901:910 arg1 results 912:918 separation results 901:918 separation results 901:918 37 N-glycan peaks were observed from separation results, with confirmed structure for most glycans. 29126476 5 21 theme bio-statistical 807:821 arg1 methods 823:829 bio-statistical methods 807:829 bio-statistical methods 807:829 Due to complexity of the study data, bio-statistical methods were applied to data processing. 29126476 4 22 theme heart 668:672 arg1 patients 682:689 differentiating heart disease patients 652:689 differentiating heart disease patients with normal controls in response to an antiplatelet drug from hypo-responders 652:767 The application involves two biomarker studies: (1) in profiling patients with chronic kidney disease and (2) in differentiating heart disease patients with normal controls in response to an antiplatelet drug from hypo-responders. 29126476 3 23 theme high-throughput 364:378 arg1 preparation 401:411 a high-throughput GlycanAssure™ sample preparation 362:411 a high-throughput GlycanAssure™ sample preparation technology 362:422 This work demonstrates the use of a high-throughput GlycanAssure™ sample preparation technology and multi-capillary DNA analyzer for the analysis of the major N-linked glycans (N-glycans) found in human plasma. 29126476 1 24 located found 170:174 arg2 compounds 160:168 organic compounds 152:168 organic compounds found in nature 152:184 Carbohydrates form the majority of organic compounds found in nature and their presence on proteins influences many important bioactivities. 29126476 1 24 located found 170:174 arg1 nature 179:184 nature 179:184 nature 179:184 Carbohydrates form the majority of organic compounds found in nature and their presence on proteins influences many important bioactivities. 29126476 7 25 theme build 1081:1085 arg1 models 1087:1092 build models 1081:1092 build models 1081:1092 Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to build models to differentiate the patient groups. 29126476 3 26 theme multi-capillary 428:442 arg1 analyzer 448:455 multi-capillary DNA analyzer 428:455 multi-capillary DNA analyzer 428:455 This work demonstrates the use of a high-throughput GlycanAssure™ sample preparation technology and multi-capillary DNA analyzer for the analysis of the major N-linked glycans (N-glycans) found in human plasma. 29126476 3 27 theme major 481:485 arg1 glycans 496:502 the major N-linked glycans 477:502 the major N-linked glycans (N-glycans) found in human plasma 477:536 This work demonstrates the use of a high-throughput GlycanAssure™ sample preparation technology and multi-capillary DNA analyzer for the analysis of the major N-linked glycans (N-glycans) found in human plasma. 29126476 3 27 theme major 481:485 arg1 N-glycans 505:513 N-glycans 505:513 N-glycans 505:513 This work demonstrates the use of a high-throughput GlycanAssure™ sample preparation technology and multi-capillary DNA analyzer for the analysis of the major N-linked glycans (N-glycans) found in human plasma. 29126476 0 28 theme throughput 5:14 arg1 analysis 38:45 High throughput human plasma N-glycan analysis 0:45 High throughput human plasma N-glycan analysis 0:45 High throughput human plasma N-glycan analysis using DNA analyzer and multivariate analysis for biomarker discovery. 29126476 8 29 theme correct 1150:1156 arg1 classification 1158:1171 correct classification 1150:1171 correct classification of the models 1150:1185 The percentages of correct classification of the models reached 95.45% for the chronic kidney disease dataset and 85.42% for the anti-platelet drug response dataset. 29126476 4 30 from hypo-responders 753:767 arg1 drug 743:746 an antiplatelet drug 727:746 an antiplatelet drug from hypo-responders 727:767 The application involves two biomarker studies: (1) in profiling patients with chronic kidney disease and (2) in differentiating heart disease patients with normal controls in response to an antiplatelet drug from hypo-responders. 29126476 9 31 theme N-glycan 1314:1321 arg1 profiles 1323:1330 blood N-glycan profiles 1308:1330 blood N-glycan profiles 1308:1330 Given that blood N-glycan profiles had been shown to reflect certain disease states, this high-throughput platform could potentially be used for the simultaneous screening of multiple glycan biomarkers, with as little as one drop of blood sample. 29126476 9 32 theme glycan 1481:1486 arg1 biomarkers 1488:1497 multiple glycan biomarkers 1472:1497 multiple glycan biomarkers 1472:1497 Given that blood N-glycan profiles had been shown to reflect certain disease states, this high-throughput platform could potentially be used for the simultaneous screening of multiple glycan biomarkers, with as little as one drop of blood sample. 29126476 0 33 theme High 0:3 arg1 analysis 38:45 High throughput human plasma N-glycan analysis 0:45 High throughput human plasma N-glycan analysis 0:45 High throughput human plasma N-glycan analysis using DNA analyzer and multivariate analysis for biomarker discovery. 29126476 7 34 theme partial 1014:1020 arg1 squares 1028:1034 partial least squares 1014:1034 orthogonal partial least squares discriminant analysis (OPLS-DA) 1003:1066 Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to build models to differentiate the patient groups. 29126476 4 35 theme disease 674:680 arg1 patients 682:689 differentiating heart disease patients 652:689 differentiating heart disease patients with normal controls in response to an antiplatelet drug from hypo-responders 652:767 The application involves two biomarker studies: (1) in profiling patients with chronic kidney disease and (2) in differentiating heart disease patients with normal controls in response to an antiplatelet drug from hypo-responders. 29126476 3 36 theme preparation 401:411 arg1 technology 413:422 a high-throughput GlycanAssure™ sample preparation technology 362:422 a high-throughput GlycanAssure™ sample preparation technology 362:422 This work demonstrates the use of a high-throughput GlycanAssure™ sample preparation technology and multi-capillary DNA analyzer for the analysis of the major N-linked glycans (N-glycans) found in human plasma. 29126476 8 37 theme models 1180:1185 arg1 classification 1158:1171 correct classification 1150:1171 correct classification of the models 1150:1185 The percentages of correct classification of the models reached 95.45% for the chronic kidney disease dataset and 85.42% for the anti-platelet drug response dataset. 29126476 7 38 theme component 974:982 arg1 PCA 994:996 PCA 994:996 PCA 994:996 Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to build models to differentiate the patient groups. 29126476 7 38 theme component 974:982 arg1 analysis 984:991 Principal component analysis 964:991 Principal component analysis (PCA) 964:997 Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to build models to differentiate the patient groups. 29126476 5 39 theme data 801:804 arg1 complexity 777:786 complexity 777:786 complexity of the study data 777:804 Due to complexity of the study data, bio-statistical methods were applied to data processing. 29126476 8 40 theme anti-platelet 1260:1272 arg1 dataset 1288:1294 the anti-platelet drug response dataset 1256:1294 the anti-platelet drug response dataset 1256:1294 The percentages of correct classification of the models reached 95.45% for the chronic kidney disease dataset and 85.42% for the anti-platelet drug response dataset. 29126476 0 41 theme human 16:20 arg1 analysis 38:45 High throughput human plasma N-glycan analysis 0:45 High throughput human plasma N-glycan analysis 0:45 High throughput human plasma N-glycan analysis using DNA analyzer and multivariate analysis for biomarker discovery. 29126476 4 42 theme chronic 618:624 arg1 disease 633:639 chronic kidney disease 618:639 chronic kidney disease 618:639 The application involves two biomarker studies: (1) in profiling patients with chronic kidney disease and (2) in differentiating heart disease patients with normal controls in response to an antiplatelet drug from hypo-responders. 29126476 4 43 theme kidney 626:631 arg1 disease 633:639 chronic kidney disease 618:639 chronic kidney disease 618:639 The application involves two biomarker studies: (1) in profiling patients with chronic kidney disease and (2) in differentiating heart disease patients with normal controls in response to an antiplatelet drug from hypo-responders. 29126476 4 44 with patients 682:689 arg1 controls 703:710 normal controls 696:710 normal controls in response to an antiplatelet drug from hypo-responders 696:767 The application involves two biomarker studies: (1) in profiling patients with chronic kidney disease and (2) in differentiating heart disease patients with normal controls in response to an antiplatelet drug from hypo-responders. 29126476 4 44 with patients 682:689 arg1 disease 633:639 chronic kidney disease 618:639 chronic kidney disease 618:639 The application involves two biomarker studies: (1) in profiling patients with chronic kidney disease and (2) in differentiating heart disease patients with normal controls in response to an antiplatelet drug from hypo-responders. 29126476 5 45 theme data 847:850 arg1 processing 852:861 data processing 847:861 data processing 847:861 Due to complexity of the study data, bio-statistical methods were applied to data processing. 29126476 8 46 theme kidney 1218:1223 arg1 disease 1225:1231 the chronic kidney disease 1206:1231 the chronic kidney disease dataset 1206:1239 The percentages of correct classification of the models reached 95.45% for the chronic kidney disease dataset and 85.42% for the anti-platelet drug response dataset. 29126476 4 47 dep patients 604:611 arg1 1 588:588 1 588:588 1 588:588 The application involves two biomarker studies: (1) in profiling patients with chronic kidney disease and (2) in differentiating heart disease patients with normal controls in response to an antiplatelet drug from hypo-responders. 29126476 3 48 theme N-linked 487:494 arg1 glycans 496:502 the major N-linked glycans 477:502 the major N-linked glycans (N-glycans) found in human plasma 477:536 This work demonstrates the use of a high-throughput GlycanAssure™ sample preparation technology and multi-capillary DNA analyzer for the analysis of the major N-linked glycans (N-glycans) found in human plasma. 29126476 3 48 theme N-linked 487:494 arg1 N-glycans 505:513 N-glycans 505:513 N-glycans 505:513 This work demonstrates the use of a high-throughput GlycanAssure™ sample preparation technology and multi-capillary DNA analyzer for the analysis of the major N-linked glycans (N-glycans) found in human plasma. 29126476 0 49 theme N-glycan 29:36 arg1 analysis 38:45 High throughput human plasma N-glycan analysis 0:45 High throughput human plasma N-glycan analysis 0:45 High throughput human plasma N-glycan analysis using DNA analyzer and multivariate analysis for biomarker discovery. 29126476 9 50 theme certain 1358:1364 arg1 states 1374:1379 certain disease states 1358:1379 certain disease states 1358:1379 Given that blood N-glycan profiles had been shown to reflect certain disease states, this high-throughput platform could potentially be used for the simultaneous screening of multiple glycan biomarkers, with as little as one drop of blood sample. 29126476 5 51 theme study 795:799 arg1 data 801:804 the study data 791:804 the study data 791:804 Due to complexity of the study data, bio-statistical methods were applied to data processing. 29126476 6 52 theme N-glycan 867:874 arg1 peaks 876:880 37 N-glycan peaks 864:880 37 N-glycan peaks 864:880 37 N-glycan peaks were observed from separation results, with confirmed structure for most glycans. 29126476 0 53 theme plasma 22:27 arg1 analysis 38:45 High throughput human plasma N-glycan analysis 0:45 High throughput human plasma N-glycan analysis 0:45 High throughput human plasma N-glycan analysis using DNA analyzer and multivariate analysis for biomarker discovery. 29126476 7 54 theme squares 1028:1034 arg1 OPLS-DA 1059:1065 OPLS-DA 1059:1065 OPLS-DA 1059:1065 Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to build models to differentiate the patient groups. 29126476 7 54 theme squares 1028:1034 arg1 analysis 1049:1056 orthogonal partial least squares discriminant analysis 1003:1056 orthogonal partial least squares discriminant analysis (OPLS-DA) 1003:1066 Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to build models to differentiate the patient groups. 29126476 3 55 theme glycans 496:502 arg1 analysis 465:472 the analysis 461:472 the analysis of the major N-linked glycans (N-glycans) found in human plasma 461:536 This work demonstrates the use of a high-throughput GlycanAssure™ sample preparation technology and multi-capillary DNA analyzer for the analysis of the major N-linked glycans (N-glycans) found in human plasma. 29126476 0 56 theme DNA 53:55 arg1 analyzer 57:64 DNA analyzer 53:64 DNA analyzer 53:64 High throughput human plasma N-glycan analysis using DNA analyzer and multivariate analysis for biomarker discovery. 29126476 3 57 theme GlycanAssure™ 380:392 arg1 preparation 401:411 a high-throughput GlycanAssure™ sample preparation 362:411 a high-throughput GlycanAssure™ sample preparation technology 362:422 This work demonstrates the use of a high-throughput GlycanAssure™ sample preparation technology and multi-capillary DNA analyzer for the analysis of the major N-linked glycans (N-glycans) found in human plasma. 29126476 8 58 theme chronic 1210:1216 arg1 disease 1225:1231 the chronic kidney disease 1206:1231 the chronic kidney disease dataset 1206:1239 The percentages of correct classification of the models reached 95.45% for the chronic kidney disease dataset and 85.42% for the anti-platelet drug response dataset. 29126476 9 59 used used 1433:1436 arg2 platform 1403:1410 this high-throughput platform 1382:1410 this high-throughput platform 1382:1410 Given that blood N-glycan profiles had been shown to reflect certain disease states, this high-throughput platform could potentially be used for the simultaneous screening of multiple glycan biomarkers, with as little as one drop of blood sample. 29126476 9 60 theme biomarkers 1488:1497 arg1 screening 1459:1467 the simultaneous screening 1442:1467 the simultaneous screening of multiple glycan biomarkers 1442:1497 Given that blood N-glycan profiles had been shown to reflect certain disease states, this high-throughput platform could potentially be used for the simultaneous screening of multiple glycan biomarkers, with as little as one drop of blood sample. 29126476 7 61 theme discriminant 1036:1047 arg1 OPLS-DA 1059:1065 OPLS-DA 1059:1065 OPLS-DA 1059:1065 Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to build models to differentiate the patient groups. 29126476 7 61 theme discriminant 1036:1047 arg1 analysis 1049:1056 orthogonal partial least squares discriminant analysis 1003:1056 orthogonal partial least squares discriminant analysis (OPLS-DA) 1003:1066 Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to build models to differentiate the patient groups. 29126476 3 62 theme analyzer 448:455 arg1 use 355:357 the use 351:357 the use of a high-throughput GlycanAssure™ sample preparation technology and multi-capillary DNA analyzer 351:455 This work demonstrates the use of a high-throughput GlycanAssure™ sample preparation technology and multi-capillary DNA analyzer for the analysis of the major N-linked glycans (N-glycans) found in human plasma. 29126476 6 63 theme most 950:953 arg1 glycans 955:961 most glycans 950:961 most glycans 950:961 37 N-glycan peaks were observed from separation results, with confirmed structure for most glycans. 29126476 9 64 theme sample 1536:1541 arg1 drop 1522:1525 as little as one drop 1505:1525 as little as one drop of blood sample 1505:1541 Given that blood N-glycan profiles had been shown to reflect certain disease states, this high-throughput platform could potentially be used for the simultaneous screening of multiple glycan biomarkers, with as little as one drop of blood sample. 29126476 1 65 from presence 196:203 arg1 proteins 208:215 proteins 208:215 proteins 208:215 Carbohydrates form the majority of organic compounds found in nature and their presence on proteins influences many important bioactivities. 29126476 3 66 theme human 525:529 arg1 plasma 531:536 human plasma 525:536 human plasma 525:536 This work demonstrates the use of a high-throughput GlycanAssure™ sample preparation technology and multi-capillary DNA analyzer for the analysis of the major N-linked glycans (N-glycans) found in human plasma. 29126476 2 67 from potential 292:300 arg1 applications 314:325 clinical applications 305:325 clinical applications 305:325 Therefore, glycan profiling shows potential in clinical applications. 29126476 4 68 theme biomarker 568:576 arg1 studies 578:584 two biomarker studies 564:584 two biomarker studies 564:584 The application involves two biomarker studies: (1) in profiling patients with chronic kidney disease and (2) in differentiating heart disease patients with normal controls in response to an antiplatelet drug from hypo-responders. 29126476 8 69 theme response 1279:1286 arg1 dataset 1288:1294 the anti-platelet drug response dataset 1256:1294 the anti-platelet drug response dataset 1256:1294 The percentages of correct classification of the models reached 95.45% for the chronic kidney disease dataset and 85.42% for the anti-platelet drug response dataset. 29126476 4 70 dep patients 682:689 arg1 2 646:646 2 646:646 2 646:646 The application involves two biomarker studies: (1) in profiling patients with chronic kidney disease and (2) in differentiating heart disease patients with normal controls in response to an antiplatelet drug from hypo-responders. 29126476 7 71 theme least 1022:1026 arg1 squares 1028:1034 partial least squares 1014:1034 orthogonal partial least squares discriminant analysis (OPLS-DA) 1003:1066 Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to build models to differentiate the patient groups. 29126476 4 72 theme antiplatelet 730:741 arg1 drug 743:746 an antiplatelet drug 727:746 an antiplatelet drug from hypo-responders 727:767 The application involves two biomarker studies: (1) in profiling patients with chronic kidney disease and (2) in differentiating heart disease patients with normal controls in response to an antiplatelet drug from hypo-responders. 29126476 1 73 theme many 228:231 arg1 bioactivities 243:255 many important bioactivities 228:255 many important bioactivities 228:255 Carbohydrates form the majority of organic compounds found in nature and their presence on proteins influences many important bioactivities. 29126476 2 74 theme glycan 269:274 arg1 profiling 276:284 glycan profiling 269:284 glycan profiling 269:284 Therefore, glycan profiling shows potential in clinical applications. 29126476 1 75 theme important 233:241 arg1 bioactivities 243:255 many important bioactivities 228:255 many important bioactivities 228:255 Carbohydrates form the majority of organic compounds found in nature and their presence on proteins influences many important bioactivities. 29126476 8 76 theme drug 1274:1277 arg1 dataset 1288:1294 the anti-platelet drug response dataset 1256:1294 the anti-platelet drug response dataset 1256:1294 The percentages of correct classification of the models reached 95.45% for the chronic kidney disease dataset and 85.42% for the anti-platelet drug response dataset. 29126476 7 77 theme orthogonal 1003:1012 arg1 OPLS-DA 1059:1065 OPLS-DA 1059:1065 OPLS-DA 1059:1065 Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to build models to differentiate the patient groups. 29126476 7 77 theme orthogonal 1003:1012 arg1 analysis 1049:1056 orthogonal partial least squares discriminant analysis 1003:1056 orthogonal partial least squares discriminant analysis (OPLS-DA) 1003:1066 Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to build models to differentiate the patient groups. 29126476 4 78 theme normal 696:701 arg1 controls 703:710 normal controls 696:710 normal controls in response to an antiplatelet drug from hypo-responders 696:767 The application involves two biomarker studies: (1) in profiling patients with chronic kidney disease and (2) in differentiating heart disease patients with normal controls in response to an antiplatelet drug from hypo-responders. 29126476 4 79 theme differentiating 652:666 arg1 patients 682:689 differentiating heart disease patients 652:689 differentiating heart disease patients with normal controls in response to an antiplatelet drug from hypo-responders 652:767 The application involves two biomarker studies: (1) in profiling patients with chronic kidney disease and (2) in differentiating heart disease patients with normal controls in response to an antiplatelet drug from hypo-responders. 29126476 3 80 theme DNA 444:446 arg1 analyzer 448:455 multi-capillary DNA analyzer 428:455 multi-capillary DNA analyzer 428:455 This work demonstrates the use of a high-throughput GlycanAssure™ sample preparation technology and multi-capillary DNA analyzer for the analysis of the major N-linked glycans (N-glycans) found in human plasma. 29126476 3 81 theme technology 413:422 arg1 use 355:357 the use 351:357 the use of a high-throughput GlycanAssure™ sample preparation technology and multi-capillary DNA analyzer 351:455 This work demonstrates the use of a high-throughput GlycanAssure™ sample preparation technology and multi-capillary DNA analyzer for the analysis of the major N-linked glycans (N-glycans) found in human plasma. 29126476 3 82 located found 516:520 arg2 N-glycans 505:513 N-glycans 505:513 N-glycans 505:513 This work demonstrates the use of a high-throughput GlycanAssure™ sample preparation technology and multi-capillary DNA analyzer for the analysis of the major N-linked glycans (N-glycans) found in human plasma. 29126476 3 82 located found 516:520 arg2 glycans 496:502 the major N-linked glycans 477:502 the major N-linked glycans (N-glycans) found in human plasma 477:536 This work demonstrates the use of a high-throughput GlycanAssure™ sample preparation technology and multi-capillary DNA analyzer for the analysis of the major N-linked glycans (N-glycans) found in human plasma. 29126476 3 82 located found 516:520 arg1 plasma 531:536 human plasma 525:536 human plasma 525:536 This work demonstrates the use of a high-throughput GlycanAssure™ sample preparation technology and multi-capillary DNA analyzer for the analysis of the major N-linked glycans (N-glycans) found in human plasma. 29126476 1 83 theme organic 152:158 arg1 compounds 160:168 organic compounds 152:168 organic compounds found in nature 152:184 Carbohydrates form the majority of organic compounds found in nature and their presence on proteins influences many important bioactivities. 29126476 9 84 theme disease 1366:1372 arg1 states 1374:1379 certain disease states 1358:1379 certain disease states 1358:1379 Given that blood N-glycan profiles had been shown to reflect certain disease states, this high-throughput platform could potentially be used for the simultaneous screening of multiple glycan biomarkers, with as little as one drop of blood sample. 27331624 6 0 theme prostate 1014:1021 arg1 adenocarcinoma 1023:1036 prostate adenocarcinoma 1014:1036 prostate adenocarcinoma (pAdC) 1014:1043 Chi square analysis of immunohistochemistry results showed significant upregulation of OPN (X2=25.710/p<0.001), BSP (X2=19.546/p<0.001), and DSPP (X2=8.720/p=0.003) in prostate adenocarcinoma (pAdC). 27331624 6 0 theme prostate 1014:1021 arg1 pAdC 1039:1042 pAdC 1039:1042 pAdC 1039:1042 Chi square analysis of immunohistochemistry results showed significant upregulation of OPN (X2=25.710/p<0.001), BSP (X2=19.546/p<0.001), and DSPP (X2=8.720/p=0.003) in prostate adenocarcinoma (pAdC). 27331624 10 1 theme BSP-MMP2 1495:1502 arg1 interactions 1529:1540 potential BSP-MMP2, OPN-MMP3, and DMP1-MMP9 interactions 1485:1540 potential BSP-MMP2, OPN-MMP3, and DMP1-MMP9 interactions in BPH and pAdC 1485:1556 Immunofluorescence studies confirmed BSP-MMP2, OPN-MMP3, and DMP1-MMP9 coexpression in two cancer-derived cell lines, whereas in situ proximity ligation assays confirmed potential BSP-MMP2, OPN-MMP3, and DMP1-MMP9 interactions in BPH and pAdC. 27331624 1 2 theme key 237:239 arg1 targets 241:247 key targets 237:247 key targets 237:247 The small integrin binding ligands n-linked glycoproteins (SIBLINGs) have emerged as potential diagnostic and prognostic indices, and as key targets, in cancer therapy. 27331624 2 3 dep BSP-MMP2 451:458 arg1 DMP1-MMP9 471:479 DMP1-MMP9 471:479 specific matrix metalloproteinases (MMPs): BSP-MMP2; OPN-MMP3; DMP1-MMP9 408:479 Three members of the SIBLING family: bone sialoprotein (BSP); osteopontin (OPN); and dentin matrix protein1 (DMP1), bind and interact with specific matrix metalloproteinases (MMPs): BSP-MMP2; OPN-MMP3; DMP1-MMP9, in biochemical and biologic systems. 27331624 2 3 dep BSP-MMP2 451:458 arg1 OPN-MMP3 461:468 OPN-MMP3 461:468 specific matrix metalloproteinases (MMPs): BSP-MMP2; OPN-MMP3; DMP1-MMP9 408:479 Three members of the SIBLING family: bone sialoprotein (BSP); osteopontin (OPN); and dentin matrix protein1 (DMP1), bind and interact with specific matrix metalloproteinases (MMPs): BSP-MMP2; OPN-MMP3; DMP1-MMP9, in biochemical and biologic systems. 27331624 8 4 theme MMP 1179:1181 arg1 expression 1183:1192 MMP expression 1179:1192 MMP expression 1179:1192 There were no significant differences in MMP expression between BPH and pAdC. 27331624 6 5 theme significant 905:915 arg1 X2=25.710/p<0.001 938:954 X2=25.710/p<0.001 938:954 X2=25.710/p<0.001 938:954 Chi square analysis of immunohistochemistry results showed significant upregulation of OPN (X2=25.710/p<0.001), BSP (X2=19.546/p<0.001), and DSPP (X2=8.720/p=0.003) in prostate adenocarcinoma (pAdC). 27331624 6 5 theme significant 905:915 arg1 upregulation 917:928 significant upregulation 905:928 significant upregulation of OPN (X2=25.710/p<0.001) 905:955 Chi square analysis of immunohistochemistry results showed significant upregulation of OPN (X2=25.710/p<0.001), BSP (X2=19.546/p<0.001), and DSPP (X2=8.720/p=0.003) in prostate adenocarcinoma (pAdC). 27331624 1 6 theme potential 185:193 arg1 indices 221:227 potential diagnostic and prognostic indices 185:227 potential diagnostic and prognostic indices 185:227 The small integrin binding ligands n-linked glycoproteins (SIBLINGs) have emerged as potential diagnostic and prognostic indices, and as key targets, in cancer therapy. 27331624 6 7 theme results 890:896 arg1 analysis 857:864 Chi square analysis 846:864 Chi square analysis of immunohistochemistry results 846:896 Chi square analysis of immunohistochemistry results showed significant upregulation of OPN (X2=25.710/p<0.001), BSP (X2=19.546/p<0.001), and DSPP (X2=8.720/p=0.003) in prostate adenocarcinoma (pAdC). 27331624 7 8 theme benign 1084:1089 arg1 BPH 1113:1115 BPH 1113:1115 BPH; X2=44.153/p<0.001 1113:1134 MEPE was significantly upregulated in benign prostate hyperplasia (BPH; X2=44.153/p<0.001). 27331624 7 8 theme benign 1084:1089 arg1 hyperplasia 1100:1110 benign prostate hyperplasia 1084:1110 benign prostate hyperplasia (BPH; X2=44.153/p<0.001) 1084:1135 MEPE was significantly upregulated in benign prostate hyperplasia (BPH; X2=44.153/p<0.001). 27331624 2 9 dep members 275:281 arg1 members 275:281 Three members 269:281 Three members of the SIBLING family 269:303 Three members of the SIBLING family: bone sialoprotein (BSP); osteopontin (OPN); and dentin matrix protein1 (DMP1), bind and interact with specific matrix metalloproteinases (MMPs): BSP-MMP2; OPN-MMP3; DMP1-MMP9, in biochemical and biologic systems. 27331624 2 9 dep members 275:281 arg1 OPN 344:346 OPN 344:346 OPN 344:346 Three members of the SIBLING family: bone sialoprotein (BSP); osteopontin (OPN); and dentin matrix protein1 (DMP1), bind and interact with specific matrix metalloproteinases (MMPs): BSP-MMP2; OPN-MMP3; DMP1-MMP9, in biochemical and biologic systems. 27331624 2 9 dep members 275:281 arg1 protein1 368:375 dentin matrix protein1 354:375 dentin matrix protein1 (DMP1) 354:382 Three members of the SIBLING family: bone sialoprotein (BSP); osteopontin (OPN); and dentin matrix protein1 (DMP1), bind and interact with specific matrix metalloproteinases (MMPs): BSP-MMP2; OPN-MMP3; DMP1-MMP9, in biochemical and biologic systems. 27331624 2 9 dep members 275:281 arg1 sialoprotein 311:322 bone sialoprotein 306:322 bone sialoprotein (BSP) 306:328 Three members of the SIBLING family: bone sialoprotein (BSP); osteopontin (OPN); and dentin matrix protein1 (DMP1), bind and interact with specific matrix metalloproteinases (MMPs): BSP-MMP2; OPN-MMP3; DMP1-MMP9, in biochemical and biologic systems. 27331624 2 9 dep members 275:281 arg1 DMP1 378:381 DMP1 378:381 DMP1 378:381 Three members of the SIBLING family: bone sialoprotein (BSP); osteopontin (OPN); and dentin matrix protein1 (DMP1), bind and interact with specific matrix metalloproteinases (MMPs): BSP-MMP2; OPN-MMP3; DMP1-MMP9, in biochemical and biologic systems. 27331624 2 9 dep members 275:281 arg1 BSP 325:327 BSP 325:327 BSP 325:327 Three members of the SIBLING family: bone sialoprotein (BSP); osteopontin (OPN); and dentin matrix protein1 (DMP1), bind and interact with specific matrix metalloproteinases (MMPs): BSP-MMP2; OPN-MMP3; DMP1-MMP9, in biochemical and biologic systems. 27331624 2 9 dep members 275:281 arg1 osteopontin 331:341 osteopontin 331:341 osteopontin (OPN) 331:347 Three members of the SIBLING family: bone sialoprotein (BSP); osteopontin (OPN); and dentin matrix protein1 (DMP1), bind and interact with specific matrix metalloproteinases (MMPs): BSP-MMP2; OPN-MMP3; DMP1-MMP9, in biochemical and biologic systems. 27331624 11 10 theme SIBLING-MMP 1593:1603 arg1 interaction 1605:1615 SIBLING-MMP interaction 1593:1615 SIBLING-MMP interaction 1593:1615 Our reports provide evidence that SIBLING-MMP interaction may play a role in the progression of BPH to pAdC. 27331624 8 11 from differences 1164:1174 arg1 expression 1183:1192 MMP expression 1179:1192 MMP expression 1179:1192 There were no significant differences in MMP expression between BPH and pAdC. 27331624 1 12 theme small 104:108 arg1 ligands 127:133 The small integrin binding ligands 100:133 The small integrin binding ligands n-linked glycoproteins (SIBLINGs) 100:167 The small integrin binding ligands n-linked glycoproteins (SIBLINGs) have emerged as potential diagnostic and prognostic indices, and as key targets, in cancer therapy. 27331624 6 13 theme square 850:855 arg1 analysis 857:864 Chi square analysis 846:864 Chi square analysis of immunohistochemistry results 846:896 Chi square analysis of immunohistochemistry results showed significant upregulation of OPN (X2=25.710/p<0.001), BSP (X2=19.546/p<0.001), and DSPP (X2=8.720/p=0.003) in prostate adenocarcinoma (pAdC). 27331624 1 14 gly glycoproteins 144:156 arg1 SIBLINGs 159:166 SIBLINGs 159:166 SIBLINGs 159:166 The small integrin binding ligands n-linked glycoproteins (SIBLINGs) have emerged as potential diagnostic and prognostic indices, and as key targets, in cancer therapy. 27331624 1 14 gly glycoproteins 144:156 arg1 glycoproteins 144:156 n-linked glycoproteins 135:156 The small integrin binding ligands n-linked glycoproteins (SIBLINGs) 100:167 The small integrin binding ligands n-linked glycoproteins (SIBLINGs) have emerged as potential diagnostic and prognostic indices, and as key targets, in cancer therapy. 27331624 1 15 theme binding 119:125 arg1 ligands 127:133 The small integrin binding ligands 100:133 The small integrin binding ligands n-linked glycoproteins (SIBLINGs) 100:167 The small integrin binding ligands n-linked glycoproteins (SIBLINGs) have emerged as potential diagnostic and prognostic indices, and as key targets, in cancer therapy. 27331624 2 16 theme matrix 417:422 arg1 MMPs 444:447 MMPs 444:447 MMPs 444:447 Three members of the SIBLING family: bone sialoprotein (BSP); osteopontin (OPN); and dentin matrix protein1 (DMP1), bind and interact with specific matrix metalloproteinases (MMPs): BSP-MMP2; OPN-MMP3; DMP1-MMP9, in biochemical and biologic systems. 27331624 2 16 theme matrix 417:422 arg1 metalloproteinases 424:441 specific matrix metalloproteinases 408:441 specific matrix metalloproteinases (MMPs): BSP-MMP2; OPN-MMP3; DMP1-MMP9 408:479 Three members of the SIBLING family: bone sialoprotein (BSP); osteopontin (OPN); and dentin matrix protein1 (DMP1), bind and interact with specific matrix metalloproteinases (MMPs): BSP-MMP2; OPN-MMP3; DMP1-MMP9, in biochemical and biologic systems. 27331624 5 17 theme potential 801:809 arg1 interaction 811:821 potential interaction 801:821 potential interaction 801:821 In this study, we investigated SIBLING-MMP expression and potential interaction in prostate neoplasms. 27331624 10 18 link cancer-derived 1406:1419 arg1 lines 1426:1430 two cancer-derived cell lines 1402:1430 two cancer-derived cell lines 1402:1430 Immunofluorescence studies confirmed BSP-MMP2, OPN-MMP3, and DMP1-MMP9 coexpression in two cancer-derived cell lines, whereas in situ proximity ligation assays confirmed potential BSP-MMP2, OPN-MMP3, and DMP1-MMP9 interactions in BPH and pAdC. 27331624 0 19 theme benign 59:64 arg1 neoplasms 89:97 human benign and malignant prostate neoplasms 53:97 human benign and malignant prostate neoplasms 53:97 Expression of the SIBLINGs and their MMP partners in human benign and malignant prostate neoplasms. 27331624 9 20 theme Western 1216:1222 arg1 analysis 1229:1236 Western blot analysis 1216:1236 Western blot analysis 1216:1236 Western blot analysis showed significantly elevated BSP and DSPP in prostate cancer-derived cells. 27331624 5 21 from interaction 811:821 arg1 neoplasms 835:843 prostate neoplasms 826:843 prostate neoplasms 826:843 In this study, we investigated SIBLING-MMP expression and potential interaction in prostate neoplasms. 27331624 0 22 from Expression 0:9 arg1 neoplasms 89:97 human benign and malignant prostate neoplasms 53:97 human benign and malignant prostate neoplasms 53:97 Expression of the SIBLINGs and their MMP partners in human benign and malignant prostate neoplasms. 27331624 0 23 theme malignant 70:78 arg1 neoplasms 89:97 human benign and malignant prostate neoplasms 53:97 human benign and malignant prostate neoplasms 53:97 Expression of the SIBLINGs and their MMP partners in human benign and malignant prostate neoplasms. 27331624 10 24 theme cell 1421:1424 arg1 lines 1426:1430 two cancer-derived cell lines 1402:1430 two cancer-derived cell lines 1402:1430 Immunofluorescence studies confirmed BSP-MMP2, OPN-MMP3, and DMP1-MMP9 coexpression in two cancer-derived cell lines, whereas in situ proximity ligation assays confirmed potential BSP-MMP2, OPN-MMP3, and DMP1-MMP9 interactions in BPH and pAdC. 27331624 4 25 theme specific 643:650 arg1 pairing 664:670 The specific SIBLING-MMP pairing 639:670 The specific SIBLING-MMP pairing reported in some cancers 639:695 The specific SIBLING-MMP pairing reported in some cancers have not been reported in prostate neoplasms. 27331624 11 26 theme BPH 1655:1657 arg1 progression 1640:1650 the progression 1636:1650 the progression of BPH to pAdC 1636:1665 Our reports provide evidence that SIBLING-MMP interaction may play a role in the progression of BPH to pAdC. 27331624 10 27 theme proximity 1449:1457 arg1 assays 1468:1473 in situ proximity ligation assays 1441:1473 in situ proximity ligation assays 1441:1473 Immunofluorescence studies confirmed BSP-MMP2, OPN-MMP3, and DMP1-MMP9 coexpression in two cancer-derived cell lines, whereas in situ proximity ligation assays confirmed potential BSP-MMP2, OPN-MMP3, and DMP1-MMP9 interactions in BPH and pAdC. 27331624 1 28 dep ligands 127:133 arg1 SIBLINGs 159:166 SIBLINGs 159:166 SIBLINGs 159:166 The small integrin binding ligands n-linked glycoproteins (SIBLINGs) have emerged as potential diagnostic and prognostic indices, and as key targets, in cancer therapy. 27331624 1 28 dep ligands 127:133 arg1 glycoproteins 144:156 n-linked glycoproteins 135:156 The small integrin binding ligands n-linked glycoproteins (SIBLINGs) 100:167 The small integrin binding ligands n-linked glycoproteins (SIBLINGs) have emerged as potential diagnostic and prognostic indices, and as key targets, in cancer therapy. 27331624 2 29 theme dentin 354:359 arg1 members 275:281 Three members 269:281 Three members of the SIBLING family 269:303 Three members of the SIBLING family: bone sialoprotein (BSP); osteopontin (OPN); and dentin matrix protein1 (DMP1), bind and interact with specific matrix metalloproteinases (MMPs): BSP-MMP2; OPN-MMP3; DMP1-MMP9, in biochemical and biologic systems. 27331624 2 29 theme dentin 354:359 arg1 DMP1 378:381 DMP1 378:381 DMP1 378:381 Three members of the SIBLING family: bone sialoprotein (BSP); osteopontin (OPN); and dentin matrix protein1 (DMP1), bind and interact with specific matrix metalloproteinases (MMPs): BSP-MMP2; OPN-MMP3; DMP1-MMP9, in biochemical and biologic systems. 27331624 2 29 theme dentin 354:359 arg1 protein1 368:375 dentin matrix protein1 354:375 dentin matrix protein1 (DMP1) 354:382 Three members of the SIBLING family: bone sialoprotein (BSP); osteopontin (OPN); and dentin matrix protein1 (DMP1), bind and interact with specific matrix metalloproteinases (MMPs): BSP-MMP2; OPN-MMP3; DMP1-MMP9, in biochemical and biologic systems. 27331624 7 30 theme prostate 1091:1098 arg1 BPH 1113:1115 BPH 1113:1115 BPH; X2=44.153/p<0.001 1113:1134 MEPE was significantly upregulated in benign prostate hyperplasia (BPH; X2=44.153/p<0.001). 27331624 7 30 theme prostate 1091:1098 arg1 hyperplasia 1100:1110 benign prostate hyperplasia 1084:1110 benign prostate hyperplasia (BPH; X2=44.153/p<0.001) 1084:1135 MEPE was significantly upregulated in benign prostate hyperplasia (BPH; X2=44.153/p<0.001). 27331624 2 31 dep metalloproteinases 424:441 arg1 BSP-MMP2 451:458 BSP-MMP2 451:458 specific matrix metalloproteinases (MMPs): BSP-MMP2; OPN-MMP3; DMP1-MMP9 408:479 Three members of the SIBLING family: bone sialoprotein (BSP); osteopontin (OPN); and dentin matrix protein1 (DMP1), bind and interact with specific matrix metalloproteinases (MMPs): BSP-MMP2; OPN-MMP3; DMP1-MMP9, in biochemical and biologic systems. 27331624 10 32 theme in 1441:1442 arg1 assays 1468:1473 in situ proximity ligation assays 1441:1473 in situ proximity ligation assays 1441:1473 Immunofluorescence studies confirmed BSP-MMP2, OPN-MMP3, and DMP1-MMP9 coexpression in two cancer-derived cell lines, whereas in situ proximity ligation assays confirmed potential BSP-MMP2, OPN-MMP3, and DMP1-MMP9 interactions in BPH and pAdC. 27331624 3 33 theme dentin 552:557 arg1 DSPP 580:583 DSPP 580:583 DSPP 580:583 The other two family members are dentin sialophosphoprotein (DSPP) and matrix extracellular phosphoglycoprotein (MEPE). 27331624 3 33 theme dentin 552:557 arg1 members 540:546 The other two family members 519:546 The other two family members 519:546 The other two family members are dentin sialophosphoprotein (DSPP) and matrix extracellular phosphoglycoprotein (MEPE). 27331624 3 33 theme dentin 552:557 arg1 sialophosphoprotein 559:577 dentin sialophosphoprotein 552:577 dentin sialophosphoprotein (DSPP) 552:584 The other two family members are dentin sialophosphoprotein (DSPP) and matrix extracellular phosphoglycoprotein (MEPE). 27331624 4 34 theme prostate 723:730 arg1 neoplasms 732:740 prostate neoplasms 723:740 prostate neoplasms 723:740 The specific SIBLING-MMP pairing reported in some cancers have not been reported in prostate neoplasms. 27331624 9 35 theme prostate 1284:1291 arg1 cells 1308:1312 prostate cancer-derived cells 1284:1312 prostate cancer-derived cells 1284:1312 Western blot analysis showed significantly elevated BSP and DSPP in prostate cancer-derived cells. 27331624 10 36 theme potential 1485:1493 arg1 interactions 1529:1540 potential BSP-MMP2, OPN-MMP3, and DMP1-MMP9 interactions 1485:1540 potential BSP-MMP2, OPN-MMP3, and DMP1-MMP9 interactions in BPH and pAdC 1485:1556 Immunofluorescence studies confirmed BSP-MMP2, OPN-MMP3, and DMP1-MMP9 coexpression in two cancer-derived cell lines, whereas in situ proximity ligation assays confirmed potential BSP-MMP2, OPN-MMP3, and DMP1-MMP9 interactions in BPH and pAdC. 27331624 2 37 theme bone 306:309 arg1 members 275:281 Three members 269:281 Three members of the SIBLING family 269:303 Three members of the SIBLING family: bone sialoprotein (BSP); osteopontin (OPN); and dentin matrix protein1 (DMP1), bind and interact with specific matrix metalloproteinases (MMPs): BSP-MMP2; OPN-MMP3; DMP1-MMP9, in biochemical and biologic systems. 27331624 2 37 theme bone 306:309 arg1 BSP 325:327 BSP 325:327 BSP 325:327 Three members of the SIBLING family: bone sialoprotein (BSP); osteopontin (OPN); and dentin matrix protein1 (DMP1), bind and interact with specific matrix metalloproteinases (MMPs): BSP-MMP2; OPN-MMP3; DMP1-MMP9, in biochemical and biologic systems. 27331624 2 37 theme bone 306:309 arg1 sialoprotein 311:322 bone sialoprotein 306:322 bone sialoprotein (BSP) 306:328 Three members of the SIBLING family: bone sialoprotein (BSP); osteopontin (OPN); and dentin matrix protein1 (DMP1), bind and interact with specific matrix metalloproteinases (MMPs): BSP-MMP2; OPN-MMP3; DMP1-MMP9, in biochemical and biologic systems. 27331624 0 38 theme MMP 37:39 arg1 partners 41:48 their MMP partners 31:48 their MMP partners 31:48 Expression of the SIBLINGs and their MMP partners in human benign and malignant prostate neoplasms. 27331624 9 39 dep showed 1238:1243 arg1 elevated 1259:1266 elevated 1259:1266 showed significantly elevated BSP and DSPP in prostate cancer-derived cells 1238:1312 Western blot analysis showed significantly elevated BSP and DSPP in prostate cancer-derived cells. 27331624 2 40 theme family 298:303 arg1 members 275:281 Three members 269:281 Three members of the SIBLING family 269:303 Three members of the SIBLING family: bone sialoprotein (BSP); osteopontin (OPN); and dentin matrix protein1 (DMP1), bind and interact with specific matrix metalloproteinases (MMPs): BSP-MMP2; OPN-MMP3; DMP1-MMP9, in biochemical and biologic systems. 27331624 2 40 theme family 298:303 arg1 protein1 368:375 dentin matrix protein1 354:375 dentin matrix protein1 (DMP1) 354:382 Three members of the SIBLING family: bone sialoprotein (BSP); osteopontin (OPN); and dentin matrix protein1 (DMP1), bind and interact with specific matrix metalloproteinases (MMPs): BSP-MMP2; OPN-MMP3; DMP1-MMP9, in biochemical and biologic systems. 27331624 2 40 theme family 298:303 arg1 sialoprotein 311:322 bone sialoprotein 306:322 bone sialoprotein (BSP) 306:328 Three members of the SIBLING family: bone sialoprotein (BSP); osteopontin (OPN); and dentin matrix protein1 (DMP1), bind and interact with specific matrix metalloproteinases (MMPs): BSP-MMP2; OPN-MMP3; DMP1-MMP9, in biochemical and biologic systems. 27331624 2 40 theme family 298:303 arg1 osteopontin 331:341 osteopontin 331:341 osteopontin (OPN) 331:347 Three members of the SIBLING family: bone sialoprotein (BSP); osteopontin (OPN); and dentin matrix protein1 (DMP1), bind and interact with specific matrix metalloproteinases (MMPs): BSP-MMP2; OPN-MMP3; DMP1-MMP9, in biochemical and biologic systems. 27331624 1 41 theme prognostic 210:219 arg1 indices 221:227 potential diagnostic and prognostic indices 185:227 potential diagnostic and prognostic indices 185:227 The small integrin binding ligands n-linked glycoproteins (SIBLINGs) have emerged as potential diagnostic and prognostic indices, and as key targets, in cancer therapy. 27331624 1 42 theme n-linked 135:142 arg1 SIBLINGs 159:166 SIBLINGs 159:166 SIBLINGs 159:166 The small integrin binding ligands n-linked glycoproteins (SIBLINGs) have emerged as potential diagnostic and prognostic indices, and as key targets, in cancer therapy. 27331624 1 42 theme n-linked 135:142 arg1 glycoproteins 144:156 n-linked glycoproteins 135:156 The small integrin binding ligands n-linked glycoproteins (SIBLINGs) 100:167 The small integrin binding ligands n-linked glycoproteins (SIBLINGs) have emerged as potential diagnostic and prognostic indices, and as key targets, in cancer therapy. 27331624 6 43 theme Chi 846:848 arg1 analysis 857:864 Chi square analysis 846:864 Chi square analysis of immunohistochemistry results 846:896 Chi square analysis of immunohistochemistry results showed significant upregulation of OPN (X2=25.710/p<0.001), BSP (X2=19.546/p<0.001), and DSPP (X2=8.720/p=0.003) in prostate adenocarcinoma (pAdC). 27331624 7 44 dep BPH 1113:1115 arg1 X2=44.153/p<0.001 1118:1134 X2=44.153/p<0.001 1118:1134 BPH; X2=44.153/p<0.001 1113:1134 MEPE was significantly upregulated in benign prostate hyperplasia (BPH; X2=44.153/p<0.001). 27331624 2 45 theme biologic 501:508 arg1 systems 510:516 biochemical and biologic systems 485:516 biochemical and biologic systems 485:516 Three members of the SIBLING family: bone sialoprotein (BSP); osteopontin (OPN); and dentin matrix protein1 (DMP1), bind and interact with specific matrix metalloproteinases (MMPs): BSP-MMP2; OPN-MMP3; DMP1-MMP9, in biochemical and biologic systems. 27331624 3 46 theme matrix 590:595 arg1 MEPE 632:635 MEPE 632:635 MEPE 632:635 The other two family members are dentin sialophosphoprotein (DSPP) and matrix extracellular phosphoglycoprotein (MEPE). 27331624 3 46 theme matrix 590:595 arg1 phosphoglycoprotein 611:629 matrix extracellular phosphoglycoprotein 590:629 matrix extracellular phosphoglycoprotein (MEPE) 590:636 The other two family members are dentin sialophosphoprotein (DSPP) and matrix extracellular phosphoglycoprotein (MEPE). 27331624 10 47 dep confirmed 1342:1350 arg1 whereas 1433:1439 whereas 1433:1439 whereas 1433:1439 Immunofluorescence studies confirmed BSP-MMP2, OPN-MMP3, and DMP1-MMP9 coexpression in two cancer-derived cell lines, whereas in situ proximity ligation assays confirmed potential BSP-MMP2, OPN-MMP3, and DMP1-MMP9 interactions in BPH and pAdC. 27331624 2 48 theme biochemical 485:495 arg1 systems 510:516 biochemical and biologic systems 485:516 biochemical and biologic systems 485:516 Three members of the SIBLING family: bone sialoprotein (BSP); osteopontin (OPN); and dentin matrix protein1 (DMP1), bind and interact with specific matrix metalloproteinases (MMPs): BSP-MMP2; OPN-MMP3; DMP1-MMP9, in biochemical and biologic systems. 27331624 10 49 theme DMP1-MMP9 1519:1527 arg1 interactions 1529:1540 potential BSP-MMP2, OPN-MMP3, and DMP1-MMP9 interactions 1485:1540 potential BSP-MMP2, OPN-MMP3, and DMP1-MMP9 interactions in BPH and pAdC 1485:1556 Immunofluorescence studies confirmed BSP-MMP2, OPN-MMP3, and DMP1-MMP9 coexpression in two cancer-derived cell lines, whereas in situ proximity ligation assays confirmed potential BSP-MMP2, OPN-MMP3, and DMP1-MMP9 interactions in BPH and pAdC. 27331624 10 50 theme Immunofluorescence 1315:1332 arg1 studies 1334:1340 Immunofluorescence studies 1315:1340 Immunofluorescence studies 1315:1340 Immunofluorescence studies confirmed BSP-MMP2, OPN-MMP3, and DMP1-MMP9 coexpression in two cancer-derived cell lines, whereas in situ proximity ligation assays confirmed potential BSP-MMP2, OPN-MMP3, and DMP1-MMP9 interactions in BPH and pAdC. 27331624 8 51 theme significant 1152:1162 arg1 differences 1164:1174 no significant differences 1149:1174 no significant differences in MMP expression between BPH and pAdC 1149:1213 There were no significant differences in MMP expression between BPH and pAdC. 27331624 5 52 theme SIBLING-MMP 774:784 arg1 expression 786:795 SIBLING-MMP expression 774:795 SIBLING-MMP expression 774:795 In this study, we investigated SIBLING-MMP expression and potential interaction in prostate neoplasms. 27331624 10 53 from coexpression 1386:1397 arg1 lines 1426:1430 two cancer-derived cell lines 1402:1430 two cancer-derived cell lines 1402:1430 Immunofluorescence studies confirmed BSP-MMP2, OPN-MMP3, and DMP1-MMP9 coexpression in two cancer-derived cell lines, whereas in situ proximity ligation assays confirmed potential BSP-MMP2, OPN-MMP3, and DMP1-MMP9 interactions in BPH and pAdC. 27331624 1 54 from targets 241:247 arg1 therapy 260:266 cancer therapy 253:266 cancer therapy 253:266 The small integrin binding ligands n-linked glycoproteins (SIBLINGs) have emerged as potential diagnostic and prognostic indices, and as key targets, in cancer therapy. 27331624 1 55 theme diagnostic 195:204 arg1 indices 221:227 potential diagnostic and prognostic indices 185:227 potential diagnostic and prognostic indices 185:227 The small integrin binding ligands n-linked glycoproteins (SIBLINGs) have emerged as potential diagnostic and prognostic indices, and as key targets, in cancer therapy. 27331624 6 56 theme immunohistochemistry 869:888 arg1 results 890:896 immunohistochemistry results 869:896 immunohistochemistry results 869:896 Chi square analysis of immunohistochemistry results showed significant upregulation of OPN (X2=25.710/p<0.001), BSP (X2=19.546/p<0.001), and DSPP (X2=8.720/p=0.003) in prostate adenocarcinoma (pAdC). 27331624 10 57 dep in 1441:1442 arg1 situ 1444:1447 situ 1444:1447 situ 1444:1447 Immunofluorescence studies confirmed BSP-MMP2, OPN-MMP3, and DMP1-MMP9 coexpression in two cancer-derived cell lines, whereas in situ proximity ligation assays confirmed potential BSP-MMP2, OPN-MMP3, and DMP1-MMP9 interactions in BPH and pAdC. 27331624 5 58 theme prostate 826:833 arg1 neoplasms 835:843 prostate neoplasms 826:843 prostate neoplasms 826:843 In this study, we investigated SIBLING-MMP expression and potential interaction in prostate neoplasms. 27331624 3 59 theme other 523:527 arg1 members 540:546 The other two family members 519:546 The other two family members 519:546 The other two family members are dentin sialophosphoprotein (DSPP) and matrix extracellular phosphoglycoprotein (MEPE). 27331624 3 59 theme other 523:527 arg1 sialophosphoprotein 559:577 dentin sialophosphoprotein 552:577 dentin sialophosphoprotein (DSPP) 552:584 The other two family members are dentin sialophosphoprotein (DSPP) and matrix extracellular phosphoglycoprotein (MEPE). 27331624 1 60 theme integrin 110:117 arg1 ligands 127:133 The small integrin binding ligands 100:133 The small integrin binding ligands n-linked glycoproteins (SIBLINGs) 100:167 The small integrin binding ligands n-linked glycoproteins (SIBLINGs) have emerged as potential diagnostic and prognostic indices, and as key targets, in cancer therapy. 27331624 0 61 theme human 53:57 arg1 neoplasms 89:97 human benign and malignant prostate neoplasms 53:97 human benign and malignant prostate neoplasms 53:97 Expression of the SIBLINGs and their MMP partners in human benign and malignant prostate neoplasms. 27331624 5 62 from expression 786:795 arg1 neoplasms 835:843 prostate neoplasms 826:843 prostate neoplasms 826:843 In this study, we investigated SIBLING-MMP expression and potential interaction in prostate neoplasms. 27331624 2 63 theme specific 408:415 arg1 MMPs 444:447 MMPs 444:447 MMPs 444:447 Three members of the SIBLING family: bone sialoprotein (BSP); osteopontin (OPN); and dentin matrix protein1 (DMP1), bind and interact with specific matrix metalloproteinases (MMPs): BSP-MMP2; OPN-MMP3; DMP1-MMP9, in biochemical and biologic systems. 27331624 2 63 theme specific 408:415 arg1 metalloproteinases 424:441 specific matrix metalloproteinases 408:441 specific matrix metalloproteinases (MMPs): BSP-MMP2; OPN-MMP3; DMP1-MMP9 408:479 Three members of the SIBLING family: bone sialoprotein (BSP); osteopontin (OPN); and dentin matrix protein1 (DMP1), bind and interact with specific matrix metalloproteinases (MMPs): BSP-MMP2; OPN-MMP3; DMP1-MMP9, in biochemical and biologic systems. 27331624 0 64 theme prostate 80:87 arg1 neoplasms 89:97 human benign and malignant prostate neoplasms 53:97 human benign and malignant prostate neoplasms 53:97 Expression of the SIBLINGs and their MMP partners in human benign and malignant prostate neoplasms. 27331624 9 65 theme blot 1224:1227 arg1 analysis 1229:1236 Western blot analysis 1216:1236 Western blot analysis 1216:1236 Western blot analysis showed significantly elevated BSP and DSPP in prostate cancer-derived cells. 27331624 6 66 theme OPN 933:935 arg1 X2=19.546/p<0.001 963:979 X2=19.546/p<0.001 963:979 X2=19.546/p<0.001 963:979 Chi square analysis of immunohistochemistry results showed significant upregulation of OPN (X2=25.710/p<0.001), BSP (X2=19.546/p<0.001), and DSPP (X2=8.720/p=0.003) in prostate adenocarcinoma (pAdC). 27331624 6 66 theme OPN 933:935 arg1 X2=25.710/p<0.001 938:954 X2=25.710/p<0.001 938:954 X2=25.710/p<0.001 938:954 Chi square analysis of immunohistochemistry results showed significant upregulation of OPN (X2=25.710/p<0.001), BSP (X2=19.546/p<0.001), and DSPP (X2=8.720/p=0.003) in prostate adenocarcinoma (pAdC). 27331624 6 66 theme OPN 933:935 arg1 upregulation 917:928 significant upregulation 905:928 significant upregulation of OPN (X2=25.710/p<0.001) 905:955 Chi square analysis of immunohistochemistry results showed significant upregulation of OPN (X2=25.710/p<0.001), BSP (X2=19.546/p<0.001), and DSPP (X2=8.720/p=0.003) in prostate adenocarcinoma (pAdC). 27331624 6 66 theme OPN 933:935 arg1 BSP 958:960 BSP 958:960 BSP (X2=19.546/p<0.001) 958:980 Chi square analysis of immunohistochemistry results showed significant upregulation of OPN (X2=25.710/p<0.001), BSP (X2=19.546/p<0.001), and DSPP (X2=8.720/p=0.003) in prostate adenocarcinoma (pAdC). 27331624 6 66 theme OPN 933:935 arg1 DSPP 987:990 DSPP 987:990 DSPP (X2=8.720/p=0.003) 987:1009 Chi square analysis of immunohistochemistry results showed significant upregulation of OPN (X2=25.710/p<0.001), BSP (X2=19.546/p<0.001), and DSPP (X2=8.720/p=0.003) in prostate adenocarcinoma (pAdC). 27331624 6 66 theme OPN 933:935 arg1 X2=8.720/p=0.003 993:1008 X2=8.720/p=0.003 993:1008 X2=8.720/p=0.003 993:1008 Chi square analysis of immunohistochemistry results showed significant upregulation of OPN (X2=25.710/p<0.001), BSP (X2=19.546/p<0.001), and DSPP (X2=8.720/p=0.003) in prostate adenocarcinoma (pAdC). 27331624 10 67 theme DMP1-MMP9 1376:1384 arg1 coexpression 1386:1397 DMP1-MMP9 coexpression 1376:1397 DMP1-MMP9 coexpression 1376:1397 Immunofluorescence studies confirmed BSP-MMP2, OPN-MMP3, and DMP1-MMP9 coexpression in two cancer-derived cell lines, whereas in situ proximity ligation assays confirmed potential BSP-MMP2, OPN-MMP3, and DMP1-MMP9 interactions in BPH and pAdC. 27331624 9 68 from DSPP 1276:1279 arg1 cells 1308:1312 prostate cancer-derived cells 1284:1312 prostate cancer-derived cells 1284:1312 Western blot analysis showed significantly elevated BSP and DSPP in prostate cancer-derived cells. 27331624 9 69 from BSP 1268:1270 arg1 cells 1308:1312 prostate cancer-derived cells 1284:1312 prostate cancer-derived cells 1284:1312 Western blot analysis showed significantly elevated BSP and DSPP in prostate cancer-derived cells. 27331624 10 70 theme cancer-derived 1406:1419 arg1 lines 1426:1430 two cancer-derived cell lines 1402:1430 two cancer-derived cell lines 1402:1430 Immunofluorescence studies confirmed BSP-MMP2, OPN-MMP3, and DMP1-MMP9 coexpression in two cancer-derived cell lines, whereas in situ proximity ligation assays confirmed potential BSP-MMP2, OPN-MMP3, and DMP1-MMP9 interactions in BPH and pAdC. 27331624 0 71 theme SIBLINGs 18:25 arg1 Expression 0:9 Expression 0:9 Expression of the SIBLINGs and their MMP partners in human benign and malignant prostate neoplasms. 0:98 Expression of the SIBLINGs and their MMP partners in human benign and malignant prostate neoplasms. 27331624 1 72 theme cancer 253:258 arg1 therapy 260:266 cancer therapy 253:266 cancer therapy 253:266 The small integrin binding ligands n-linked glycoproteins (SIBLINGs) have emerged as potential diagnostic and prognostic indices, and as key targets, in cancer therapy. 27331624 2 73 theme matrix 361:366 arg1 members 275:281 Three members 269:281 Three members of the SIBLING family 269:303 Three members of the SIBLING family: bone sialoprotein (BSP); osteopontin (OPN); and dentin matrix protein1 (DMP1), bind and interact with specific matrix metalloproteinases (MMPs): BSP-MMP2; OPN-MMP3; DMP1-MMP9, in biochemical and biologic systems. 27331624 2 73 theme matrix 361:366 arg1 DMP1 378:381 DMP1 378:381 DMP1 378:381 Three members of the SIBLING family: bone sialoprotein (BSP); osteopontin (OPN); and dentin matrix protein1 (DMP1), bind and interact with specific matrix metalloproteinases (MMPs): BSP-MMP2; OPN-MMP3; DMP1-MMP9, in biochemical and biologic systems. 27331624 2 73 theme matrix 361:366 arg1 protein1 368:375 dentin matrix protein1 354:375 dentin matrix protein1 (DMP1) 354:382 Three members of the SIBLING family: bone sialoprotein (BSP); osteopontin (OPN); and dentin matrix protein1 (DMP1), bind and interact with specific matrix metalloproteinases (MMPs): BSP-MMP2; OPN-MMP3; DMP1-MMP9, in biochemical and biologic systems. 27331624 4 74 theme SIBLING-MMP 652:662 arg1 pairing 664:670 The specific SIBLING-MMP pairing 639:670 The specific SIBLING-MMP pairing reported in some cancers 639:695 The specific SIBLING-MMP pairing reported in some cancers have not been reported in prostate neoplasms. 27331624 3 75 gly phosphoglycoprotein 611:629 arg1 MEPE 632:635 MEPE 632:635 MEPE 632:635 The other two family members are dentin sialophosphoprotein (DSPP) and matrix extracellular phosphoglycoprotein (MEPE). 27331624 3 75 gly phosphoglycoprotein 611:629 arg1 phosphoglycoprotein 611:629 matrix extracellular phosphoglycoprotein 590:629 matrix extracellular phosphoglycoprotein (MEPE) 590:636 The other two family members are dentin sialophosphoprotein (DSPP) and matrix extracellular phosphoglycoprotein (MEPE). 27331624 1 76 link n-linked 135:142 arg1 SIBLINGs 159:166 SIBLINGs 159:166 SIBLINGs 159:166 The small integrin binding ligands n-linked glycoproteins (SIBLINGs) have emerged as potential diagnostic and prognostic indices, and as key targets, in cancer therapy. 27331624 1 76 link n-linked 135:142 arg1 glycoproteins 144:156 n-linked glycoproteins 135:156 The small integrin binding ligands n-linked glycoproteins (SIBLINGs) 100:167 The small integrin binding ligands n-linked glycoproteins (SIBLINGs) have emerged as potential diagnostic and prognostic indices, and as key targets, in cancer therapy. 27331624 3 77 theme family 533:538 arg1 members 540:546 The other two family members 519:546 The other two family members 519:546 The other two family members are dentin sialophosphoprotein (DSPP) and matrix extracellular phosphoglycoprotein (MEPE). 27331624 3 77 theme family 533:538 arg1 sialophosphoprotein 559:577 dentin sialophosphoprotein 552:577 dentin sialophosphoprotein (DSPP) 552:584 The other two family members are dentin sialophosphoprotein (DSPP) and matrix extracellular phosphoglycoprotein (MEPE). 27331624 0 78 theme partners 41:48 arg1 Expression 0:9 Expression 0:9 Expression of the SIBLINGs and their MMP partners in human benign and malignant prostate neoplasms. 0:98 Expression of the SIBLINGs and their MMP partners in human benign and malignant prostate neoplasms. 27331624 9 79 theme cancer-derived 1293:1306 arg1 cells 1308:1312 prostate cancer-derived cells 1284:1312 prostate cancer-derived cells 1284:1312 Western blot analysis showed significantly elevated BSP and DSPP in prostate cancer-derived cells. 27331624 9 80 link cancer-derived 1293:1306 arg1 cells 1308:1312 prostate cancer-derived cells 1284:1312 prostate cancer-derived cells 1284:1312 Western blot analysis showed significantly elevated BSP and DSPP in prostate cancer-derived cells. 27331624 10 81 from BSP-MMP2 1352:1359 arg1 lines 1426:1430 two cancer-derived cell lines 1402:1430 two cancer-derived cell lines 1402:1430 Immunofluorescence studies confirmed BSP-MMP2, OPN-MMP3, and DMP1-MMP9 coexpression in two cancer-derived cell lines, whereas in situ proximity ligation assays confirmed potential BSP-MMP2, OPN-MMP3, and DMP1-MMP9 interactions in BPH and pAdC. 27331624 10 82 theme ligation 1459:1466 arg1 assays 1468:1473 in situ proximity ligation assays 1441:1473 in situ proximity ligation assays 1441:1473 Immunofluorescence studies confirmed BSP-MMP2, OPN-MMP3, and DMP1-MMP9 coexpression in two cancer-derived cell lines, whereas in situ proximity ligation assays confirmed potential BSP-MMP2, OPN-MMP3, and DMP1-MMP9 interactions in BPH and pAdC. 27331624 2 83 theme SIBLING 290:296 arg1 family 298:303 the SIBLING family 286:303 the SIBLING family 286:303 Three members of the SIBLING family: bone sialoprotein (BSP); osteopontin (OPN); and dentin matrix protein1 (DMP1), bind and interact with specific matrix metalloproteinases (MMPs): BSP-MMP2; OPN-MMP3; DMP1-MMP9, in biochemical and biologic systems. 27331624 10 84 from interactions 1529:1540 arg1 pAdC 1553:1556 pAdC 1553:1556 pAdC 1553:1556 Immunofluorescence studies confirmed BSP-MMP2, OPN-MMP3, and DMP1-MMP9 coexpression in two cancer-derived cell lines, whereas in situ proximity ligation assays confirmed potential BSP-MMP2, OPN-MMP3, and DMP1-MMP9 interactions in BPH and pAdC. 27331624 10 84 from interactions 1529:1540 arg1 BPH 1545:1547 BPH 1545:1547 BPH 1545:1547 Immunofluorescence studies confirmed BSP-MMP2, OPN-MMP3, and DMP1-MMP9 coexpression in two cancer-derived cell lines, whereas in situ proximity ligation assays confirmed potential BSP-MMP2, OPN-MMP3, and DMP1-MMP9 interactions in BPH and pAdC. 27331624 10 85 from OPN-MMP3 1362:1369 arg1 lines 1426:1430 two cancer-derived cell lines 1402:1430 two cancer-derived cell lines 1402:1430 Immunofluorescence studies confirmed BSP-MMP2, OPN-MMP3, and DMP1-MMP9 coexpression in two cancer-derived cell lines, whereas in situ proximity ligation assays confirmed potential BSP-MMP2, OPN-MMP3, and DMP1-MMP9 interactions in BPH and pAdC. 27331624 10 86 theme OPN-MMP3 1505:1512 arg1 interactions 1529:1540 potential BSP-MMP2, OPN-MMP3, and DMP1-MMP9 interactions 1485:1540 potential BSP-MMP2, OPN-MMP3, and DMP1-MMP9 interactions in BPH and pAdC 1485:1556 Immunofluorescence studies confirmed BSP-MMP2, OPN-MMP3, and DMP1-MMP9 coexpression in two cancer-derived cell lines, whereas in situ proximity ligation assays confirmed potential BSP-MMP2, OPN-MMP3, and DMP1-MMP9 interactions in BPH and pAdC. 27331624 3 87 theme extracellular 597:609 arg1 MEPE 632:635 MEPE 632:635 MEPE 632:635 The other two family members are dentin sialophosphoprotein (DSPP) and matrix extracellular phosphoglycoprotein (MEPE). 27331624 3 87 theme extracellular 597:609 arg1 phosphoglycoprotein 611:629 matrix extracellular phosphoglycoprotein 590:629 matrix extracellular phosphoglycoprotein (MEPE) 590:636 The other two family members are dentin sialophosphoprotein (DSPP) and matrix extracellular phosphoglycoprotein (MEPE). 27142667 0 0 theme single 87:92 arg1 nucleopolyhedrovirus 94:113 Helicoverpa armigera single nucleopolyhedrovirus 66:113 Helicoverpa armigera single nucleopolyhedrovirus 66:113 Characterization of the viral fibroblast growth factor homolog of Helicoverpa armigera single nucleopolyhedrovirus. 27142667 2 1 theme larvae 506:511 arg1 killing 486:492 accelerated killing 474:492 accelerated killing of infected larvae by both viruses 474:527 The function of vFGFs from Group I alphabaculoviruses, including Autographa californica multiple nucleopolyhedrovirus (AcMNPV) and Bombyx mori nucleopolyhedrovirus (BmNPV), involves accelerated killing of infected larvae by both viruses. 27142667 2 2 theme Autographa 357:366 arg1 AcMNPV 411:416 AcMNPV 411:416 AcMNPV 411:416 The function of vFGFs from Group I alphabaculoviruses, including Autographa californica multiple nucleopolyhedrovirus (AcMNPV) and Bombyx mori nucleopolyhedrovirus (BmNPV), involves accelerated killing of infected larvae by both viruses. 27142667 2 2 theme Autographa 357:366 arg1 nucleopolyhedrovirus 389:408 Autographa californica multiple nucleopolyhedrovirus 357:408 Autographa californica multiple nucleopolyhedrovirus (AcMNPV) 357:417 The function of vFGFs from Group I alphabaculoviruses, including Autographa californica multiple nucleopolyhedrovirus (AcMNPV) and Bombyx mori nucleopolyhedrovirus (BmNPV), involves accelerated killing of infected larvae by both viruses. 27142667 2 3 from function 296:303 arg1 alphabaculoviruses 327:344 Group I alphabaculoviruses 319:344 Group I alphabaculoviruses 319:344 The function of vFGFs from Group I alphabaculoviruses, including Autographa californica multiple nucleopolyhedrovirus (AcMNPV) and Bombyx mori nucleopolyhedrovirus (BmNPV), involves accelerated killing of infected larvae by both viruses. 27142667 2 3 from function 296:303 arg1 nucleopolyhedrovirus 389:408 Autographa californica multiple nucleopolyhedrovirus 357:408 Autographa californica multiple nucleopolyhedrovirus (AcMNPV) 357:417 The function of vFGFs from Group I alphabaculoviruses, including Autographa californica multiple nucleopolyhedrovirus (AcMNPV) and Bombyx mori nucleopolyhedrovirus (BmNPV), involves accelerated killing of infected larvae by both viruses. 27142667 2 3 from function 296:303 arg1 nucleopolyhedrovirus 435:454 Bombyx mori nucleopolyhedrovirus 423:454 Bombyx mori nucleopolyhedrovirus (BmNPV) 423:462 The function of vFGFs from Group I alphabaculoviruses, including Autographa californica multiple nucleopolyhedrovirus (AcMNPV) and Bombyx mori nucleopolyhedrovirus (BmNPV), involves accelerated killing of infected larvae by both viruses. 27142667 6 4 theme HearNPV 1027:1033 arg1 bacmids 1035:1041 vfgf-knockout and -repaired HearNPV bacmids 999:1041 vfgf-knockout and -repaired HearNPV bacmids 999:1041 To further study vFGF function, we constructed vfgf-knockout and -repaired HearNPV bacmids and investigated their affect in both cultured cells and insects. 27142667 0 5 theme armigera 78:85 arg1 nucleopolyhedrovirus 94:113 Helicoverpa armigera single nucleopolyhedrovirus 66:113 Helicoverpa armigera single nucleopolyhedrovirus 66:113 Characterization of the viral fibroblast growth factor homolog of Helicoverpa armigera single nucleopolyhedrovirus. 27142667 7 6 theme budded-virus 1143:1154 arg1 production 1156:1165 budded-virus production 1143:1165 budded-virus production 1143:1165 Deletion of vfgf had no effect on budded-virus production or viral DNA replication in cultured HzAM1 cells. 27142667 5 7 theme h 908:908 arg1 post-infection 910:923 16 h post-infection 905:923 16 h post-infection 905:923 The transcription and expression of vfgf was detected at 3 h and 16 h post-infection in HearNPV-infected cells. 27142667 1 8 theme multicellular 167:179 arg1 organisms 181:189 multicellular organisms 167:189 multicellular organisms 167:189 Fibroblast growth factor (FGF) is found throughout multicellular organisms; however, fgf homologs (vfgf) have only been identified among viruses in lepidopteran baculoviruses. 27142667 8 9 theme HearNPV 1248:1254 arg1 deletion 1261:1268 HearNPV vfgf deletion 1248:1268 HearNPV vfgf deletion 1248:1268 However, bioassays showed that HearNPV vfgf deletion significantly increased the median lethal dose and delayed the median lethal time by ∼12 h in the host insect when the virus was delivered orally. 27142667 5 10 theme 16 905:906 arg1 h 908:908 h 908:908 h 908:908 The transcription and expression of vfgf was detected at 3 h and 16 h post-infection in HearNPV-infected cells. 27142667 4 11 theme Helicoverpa 780:790 arg1 HearNPV 830:836 HearNPV 830:836 HearNPV 830:836 In this study, we characterized the Group II alphabaculovirus vFGF of Helicoverpa armigera single nucleopolyhedrovirus (HearNPV). 27142667 4 11 theme Helicoverpa 780:790 arg1 nucleopolyhedrovirus 808:827 Helicoverpa armigera single nucleopolyhedrovirus 780:827 Helicoverpa armigera single nucleopolyhedrovirus (HearNPV) 780:837 In this study, we characterized the Group II alphabaculovirus vFGF of Helicoverpa armigera single nucleopolyhedrovirus (HearNPV). 27142667 4 12 theme alphabaculovirus 755:770 arg1 vFGF 772:775 the Group II alphabaculovirus vFGF 742:775 the Group II alphabaculovirus vFGF of Helicoverpa armigera single nucleopolyhedrovirus (HearNPV) 742:837 In this study, we characterized the Group II alphabaculovirus vFGF of Helicoverpa armigera single nucleopolyhedrovirus (HearNPV). 27142667 0 13 theme nucleopolyhedrovirus 94:113 arg1 homolog 55:61 the viral fibroblast growth factor homolog 20:61 the viral fibroblast growth factor homolog of Helicoverpa armigera single nucleopolyhedrovirus 20:113 Characterization of the viral fibroblast growth factor homolog of Helicoverpa armigera single nucleopolyhedrovirus. 27142667 7 14 from replication 1180:1190 arg1 cells 1210:1214 cultured HzAM1 cells 1195:1214 cultured HzAM1 cells 1195:1214 Deletion of vfgf had no effect on budded-virus production or viral DNA replication in cultured HzAM1 cells. 27142667 3 15 theme alphabaculovirus 551:566 arg1 different 584:592 different 584:592 different 584:592 The vFGF of Group II alphabaculovirus is structurally different from that of Group I alphabaculovirus, with a larger C-terminal region and additional N-linked glycosylation sites. 27142667 3 15 theme alphabaculovirus 551:566 arg1 vFGF 534:537 The vFGF 530:537 The vFGF of Group II alphabaculovirus 530:566 The vFGF of Group II alphabaculovirus is structurally different from that of Group I alphabaculovirus, with a larger C-terminal region and additional N-linked glycosylation sites. 27142667 9 16 theme virulent 1467:1474 arg1 factor 1476:1481 an important virulent factor 1454:1481 an important virulent factor for HearNPV infection and propagation 1454:1519 These results suggested that vFGF is an important virulent factor for HearNPV infection and propagation in vivo. 27142667 9 16 theme virulent 1467:1474 arg1 vFGF 1446:1449 vFGF 1446:1449 vFGF 1446:1449 These results suggested that vFGF is an important virulent factor for HearNPV infection and propagation in vivo. 27142667 5 17 theme vfgf 876:879 arg1 expression 862:871 expression 862:871 expression 862:871 The transcription and expression of vfgf was detected at 3 h and 16 h post-infection in HearNPV-infected cells. 27142667 5 17 theme vfgf 876:879 arg1 transcription 844:856 transcription 844:856 transcription 844:856 The transcription and expression of vfgf was detected at 3 h and 16 h post-infection in HearNPV-infected cells. 27142667 7 18 theme vfgf 1121:1124 arg1 Deletion 1109:1116 Deletion 1109:1116 Deletion of vfgf 1109:1124 Deletion of vfgf had no effect on budded-virus production or viral DNA replication in cultured HzAM1 cells. 27142667 2 19 from alphabaculoviruses 327:344 arg1 vFGFs 308:312 vFGFs 308:312 vFGFs from Group I alphabaculoviruses, including Autographa californica multiple nucleopolyhedrovirus (AcMNPV) and Bombyx mori nucleopolyhedrovirus (BmNPV), 308:463 The function of vFGFs from Group I alphabaculoviruses, including Autographa californica multiple nucleopolyhedrovirus (AcMNPV) and Bombyx mori nucleopolyhedrovirus (BmNPV), involves accelerated killing of infected larvae by both viruses. 27142667 2 19 from alphabaculoviruses 327:344 arg1 function 296:303 The function 292:303 The function of vFGFs from Group I alphabaculoviruses, including Autographa californica multiple nucleopolyhedrovirus (AcMNPV) and Bombyx mori nucleopolyhedrovirus (BmNPV), 292:463 The function of vFGFs from Group I alphabaculoviruses, including Autographa californica multiple nucleopolyhedrovirus (AcMNPV) and Bombyx mori nucleopolyhedrovirus (BmNPV), involves accelerated killing of infected larvae by both viruses. 27142667 4 20 theme single 801:806 arg1 HearNPV 830:836 HearNPV 830:836 HearNPV 830:836 In this study, we characterized the Group II alphabaculovirus vFGF of Helicoverpa armigera single nucleopolyhedrovirus (HearNPV). 27142667 4 20 theme single 801:806 arg1 nucleopolyhedrovirus 808:827 Helicoverpa armigera single nucleopolyhedrovirus 780:827 Helicoverpa armigera single nucleopolyhedrovirus (HearNPV) 780:837 In this study, we characterized the Group II alphabaculovirus vFGF of Helicoverpa armigera single nucleopolyhedrovirus (HearNPV). 27142667 6 21 theme vfgf-knockout 999:1011 arg1 bacmids 1035:1041 vfgf-knockout and -repaired HearNPV bacmids 999:1041 vfgf-knockout and -repaired HearNPV bacmids 999:1041 To further study vFGF function, we constructed vfgf-knockout and -repaired HearNPV bacmids and investigated their affect in both cultured cells and insects. 27142667 7 22 theme viral 1170:1174 arg1 replication 1180:1190 viral DNA replication 1170:1190 viral DNA replication 1170:1190 Deletion of vfgf had no effect on budded-virus production or viral DNA replication in cultured HzAM1 cells. 27142667 3 23 theme Group 542:546 arg1 alphabaculovirus 551:566 Group II alphabaculovirus 542:566 Group II alphabaculovirus 542:566 The vFGF of Group II alphabaculovirus is structurally different from that of Group I alphabaculovirus, with a larger C-terminal region and additional N-linked glycosylation sites. 27142667 8 24 theme vfgf 1256:1259 arg1 deletion 1261:1268 HearNPV vfgf deletion 1248:1268 HearNPV vfgf deletion 1248:1268 However, bioassays showed that HearNPV vfgf deletion significantly increased the median lethal dose and delayed the median lethal time by ∼12 h in the host insect when the virus was delivered orally. 27142667 7 25 theme cultured 1195:1202 arg1 cells 1210:1214 cultured HzAM1 cells 1195:1214 cultured HzAM1 cells 1195:1214 Deletion of vfgf had no effect on budded-virus production or viral DNA replication in cultured HzAM1 cells. 27142667 2 26 theme infected 497:504 arg1 larvae 506:511 infected larvae 497:511 infected larvae 497:511 The function of vFGFs from Group I alphabaculoviruses, including Autographa californica multiple nucleopolyhedrovirus (AcMNPV) and Bombyx mori nucleopolyhedrovirus (BmNPV), involves accelerated killing of infected larvae by both viruses. 27142667 6 27 from affect 1066:1071 arg1 insects 1100:1106 insects 1100:1106 insects 1100:1106 To further study vFGF function, we constructed vfgf-knockout and -repaired HearNPV bacmids and investigated their affect in both cultured cells and insects. 27142667 6 27 from affect 1066:1071 arg1 cells 1090:1094 cultured cells 1081:1094 cultured cells 1081:1094 To further study vFGF function, we constructed vfgf-knockout and -repaired HearNPV bacmids and investigated their affect in both cultured cells and insects. 27142667 7 28 theme HzAM1 1204:1208 arg1 cells 1210:1214 cultured HzAM1 cells 1195:1214 cultured HzAM1 cells 1195:1214 Deletion of vfgf had no effect on budded-virus production or viral DNA replication in cultured HzAM1 cells. 27142667 1 29 theme lepidopteran 264:275 arg1 baculoviruses 277:289 lepidopteran baculoviruses 264:289 lepidopteran baculoviruses 264:289 Fibroblast growth factor (FGF) is found throughout multicellular organisms; however, fgf homologs (vfgf) have only been identified among viruses in lepidopteran baculoviruses. 27142667 2 30 theme vFGFs 308:312 arg1 function 296:303 The function 292:303 The function of vFGFs from Group I alphabaculoviruses, including Autographa californica multiple nucleopolyhedrovirus (AcMNPV) and Bombyx mori nucleopolyhedrovirus (BmNPV), 292:463 The function of vFGFs from Group I alphabaculoviruses, including Autographa californica multiple nucleopolyhedrovirus (AcMNPV) and Bombyx mori nucleopolyhedrovirus (BmNPV), involves accelerated killing of infected larvae by both viruses. 27142667 3 31 from that 599:602 arg1 different 584:592 different 584:592 different 584:592 The vFGF of Group II alphabaculovirus is structurally different from that of Group I alphabaculovirus, with a larger C-terminal region and additional N-linked glycosylation sites. 27142667 3 31 from that 599:602 arg1 vFGF 534:537 The vFGF 530:537 The vFGF of Group II alphabaculovirus 530:566 The vFGF of Group II alphabaculovirus is structurally different from that of Group I alphabaculovirus, with a larger C-terminal region and additional N-linked glycosylation sites. 27142667 9 32 theme important 1457:1465 arg1 factor 1476:1481 an important virulent factor 1454:1481 an important virulent factor for HearNPV infection and propagation 1454:1519 These results suggested that vFGF is an important virulent factor for HearNPV infection and propagation in vivo. 27142667 9 32 theme important 1457:1465 arg1 vFGF 1446:1449 vFGF 1446:1449 vFGF 1446:1449 These results suggested that vFGF is an important virulent factor for HearNPV infection and propagation in vivo. 27142667 0 33 theme viral 24:28 arg1 homolog 55:61 the viral fibroblast growth factor homolog 20:61 the viral fibroblast growth factor homolog of Helicoverpa armigera single nucleopolyhedrovirus 20:113 Characterization of the viral fibroblast growth factor homolog of Helicoverpa armigera single nucleopolyhedrovirus. 27142667 8 34 theme median 1333:1338 arg1 time 1347:1350 the median lethal time 1329:1350 the median lethal time 1329:1350 However, bioassays showed that HearNPV vfgf deletion significantly increased the median lethal dose and delayed the median lethal time by ∼12 h in the host insect when the virus was delivered orally. 27142667 1 35 from viruses 253:259 arg1 baculoviruses 277:289 lepidopteran baculoviruses 264:289 lepidopteran baculoviruses 264:289 Fibroblast growth factor (FGF) is found throughout multicellular organisms; however, fgf homologs (vfgf) have only been identified among viruses in lepidopteran baculoviruses. 27142667 1 36 theme Fibroblast 116:125 arg1 FGF 142:144 FGF 142:144 FGF 142:144 Fibroblast growth factor (FGF) is found throughout multicellular organisms; however, fgf homologs (vfgf) have only been identified among viruses in lepidopteran baculoviruses. 27142667 1 36 theme Fibroblast 116:125 arg1 factor 134:139 Fibroblast growth factor 116:139 Fibroblast growth factor (FGF) 116:145 Fibroblast growth factor (FGF) is found throughout multicellular organisms; however, fgf homologs (vfgf) have only been identified among viruses in lepidopteran baculoviruses. 27142667 1 37 theme fgf 201:203 arg1 homologs 205:212 fgf homologs 201:212 fgf homologs (vfgf) 201:219 Fibroblast growth factor (FGF) is found throughout multicellular organisms; however, fgf homologs (vfgf) have only been identified among viruses in lepidopteran baculoviruses. 27142667 1 37 theme fgf 201:203 arg1 vfgf 215:218 vfgf 215:218 vfgf 215:218 Fibroblast growth factor (FGF) is found throughout multicellular organisms; however, fgf homologs (vfgf) have only been identified among viruses in lepidopteran baculoviruses. 27142667 4 38 theme Group 746:750 arg1 vFGF 772:775 the Group II alphabaculovirus vFGF 742:775 the Group II alphabaculovirus vFGF of Helicoverpa armigera single nucleopolyhedrovirus (HearNPV) 742:837 In this study, we characterized the Group II alphabaculovirus vFGF of Helicoverpa armigera single nucleopolyhedrovirus (HearNPV). 27142667 8 39 theme host 1368:1371 arg1 insect 1373:1378 the host insect 1364:1378 the host insect 1364:1378 However, bioassays showed that HearNPV vfgf deletion significantly increased the median lethal dose and delayed the median lethal time by ∼12 h in the host insect when the virus was delivered orally. 27142667 9 40 theme HearNPV 1487:1493 arg1 infection 1495:1503 HearNPV infection 1487:1503 HearNPV infection 1487:1503 These results suggested that vFGF is an important virulent factor for HearNPV infection and propagation in vivo. 27142667 1 41 theme growth 127:132 arg1 FGF 142:144 FGF 142:144 FGF 142:144 Fibroblast growth factor (FGF) is found throughout multicellular organisms; however, fgf homologs (vfgf) have only been identified among viruses in lepidopteran baculoviruses. 27142667 1 41 theme growth 127:132 arg1 factor 134:139 Fibroblast growth factor 116:139 Fibroblast growth factor (FGF) 116:145 Fibroblast growth factor (FGF) is found throughout multicellular organisms; however, fgf homologs (vfgf) have only been identified among viruses in lepidopteran baculoviruses. 27142667 7 42 theme DNA 1176:1178 arg1 replication 1180:1190 viral DNA replication 1170:1190 viral DNA replication 1170:1190 Deletion of vfgf had no effect on budded-virus production or viral DNA replication in cultured HzAM1 cells. 27142667 2 43 theme mori 430:433 arg1 BmNPV 457:461 BmNPV 457:461 BmNPV 457:461 The function of vFGFs from Group I alphabaculoviruses, including Autographa californica multiple nucleopolyhedrovirus (AcMNPV) and Bombyx mori nucleopolyhedrovirus (BmNPV), involves accelerated killing of infected larvae by both viruses. 27142667 2 43 theme mori 430:433 arg1 nucleopolyhedrovirus 435:454 Bombyx mori nucleopolyhedrovirus 423:454 Bombyx mori nucleopolyhedrovirus (BmNPV) 423:462 The function of vFGFs from Group I alphabaculoviruses, including Autographa californica multiple nucleopolyhedrovirus (AcMNPV) and Bombyx mori nucleopolyhedrovirus (BmNPV), involves accelerated killing of infected larvae by both viruses. 27142667 0 44 theme growth 41:46 arg1 homolog 55:61 the viral fibroblast growth factor homolog 20:61 the viral fibroblast growth factor homolog of Helicoverpa armigera single nucleopolyhedrovirus 20:113 Characterization of the viral fibroblast growth factor homolog of Helicoverpa armigera single nucleopolyhedrovirus. 27142667 5 45 located detected 885:892 arg2 expression 862:871 expression 862:871 expression 862:871 The transcription and expression of vfgf was detected at 3 h and 16 h post-infection in HearNPV-infected cells. 27142667 5 45 located detected 885:892 arg2 transcription 844:856 transcription 844:856 transcription 844:856 The transcription and expression of vfgf was detected at 3 h and 16 h post-infection in HearNPV-infected cells. 27142667 5 45 located detected 885:892 arg1 cells 945:949 HearNPV-infected cells 928:949 HearNPV-infected cells 928:949 The transcription and expression of vfgf was detected at 3 h and 16 h post-infection in HearNPV-infected cells. 27142667 5 45 located detected 885:892 arg1 h 899:899 3 h 897:899 3 h 897:899 The transcription and expression of vfgf was detected at 3 h and 16 h post-infection in HearNPV-infected cells. 27142667 3 46 theme Group 607:611 arg1 alphabaculovirus 615:630 Group I alphabaculovirus 607:630 Group I alphabaculovirus 607:630 The vFGF of Group II alphabaculovirus is structurally different from that of Group I alphabaculovirus, with a larger C-terminal region and additional N-linked glycosylation sites. 27142667 2 47 theme Bombyx 423:428 arg1 BmNPV 457:461 BmNPV 457:461 BmNPV 457:461 The function of vFGFs from Group I alphabaculoviruses, including Autographa californica multiple nucleopolyhedrovirus (AcMNPV) and Bombyx mori nucleopolyhedrovirus (BmNPV), involves accelerated killing of infected larvae by both viruses. 27142667 2 47 theme Bombyx 423:428 arg1 nucleopolyhedrovirus 435:454 Bombyx mori nucleopolyhedrovirus 423:454 Bombyx mori nucleopolyhedrovirus (BmNPV) 423:462 The function of vFGFs from Group I alphabaculoviruses, including Autographa californica multiple nucleopolyhedrovirus (AcMNPV) and Bombyx mori nucleopolyhedrovirus (BmNPV), involves accelerated killing of infected larvae by both viruses. 27142667 0 48 theme fibroblast 30:39 arg1 homolog 55:61 the viral fibroblast growth factor homolog 20:61 the viral fibroblast growth factor homolog of Helicoverpa armigera single nucleopolyhedrovirus 20:113 Characterization of the viral fibroblast growth factor homolog of Helicoverpa armigera single nucleopolyhedrovirus. 27142667 6 49 theme vFGF 969:972 arg1 function 974:981 vFGF function 969:981 vFGF function 969:981 To further study vFGF function, we constructed vfgf-knockout and -repaired HearNPV bacmids and investigated their affect in both cultured cells and insects. 27142667 6 50 theme -repaired 1017:1025 arg1 bacmids 1035:1041 vfgf-knockout and -repaired HearNPV bacmids 999:1041 vfgf-knockout and -repaired HearNPV bacmids 999:1041 To further study vFGF function, we constructed vfgf-knockout and -repaired HearNPV bacmids and investigated their affect in both cultured cells and insects. 27142667 3 51 theme larger 640:645 arg1 region 658:663 a larger C-terminal region 638:663 a larger C-terminal region 638:663 The vFGF of Group II alphabaculovirus is structurally different from that of Group I alphabaculovirus, with a larger C-terminal region and additional N-linked glycosylation sites. 27142667 3 52 theme I 613:613 arg1 alphabaculovirus 615:630 Group I alphabaculovirus 607:630 Group I alphabaculovirus 607:630 The vFGF of Group II alphabaculovirus is structurally different from that of Group I alphabaculovirus, with a larger C-terminal region and additional N-linked glycosylation sites. 27142667 8 53 theme lethal 1305:1310 arg1 dose 1312:1315 the median lethal dose 1294:1315 the median lethal dose 1294:1315 However, bioassays showed that HearNPV vfgf deletion significantly increased the median lethal dose and delayed the median lethal time by ∼12 h in the host insect when the virus was delivered orally. 27142667 0 54 theme homolog 55:61 arg1 Characterization 0:15 Characterization 0:15 Characterization of the viral fibroblast growth factor homolog of Helicoverpa armigera single nucleopolyhedrovirus. 0:114 Characterization of the viral fibroblast growth factor homolog of Helicoverpa armigera single nucleopolyhedrovirus. 27142667 8 55 theme median 1298:1303 arg1 dose 1312:1315 the median lethal dose 1294:1315 the median lethal dose 1294:1315 However, bioassays showed that HearNPV vfgf deletion significantly increased the median lethal dose and delayed the median lethal time by ∼12 h in the host insect when the virus was delivered orally. 27142667 3 56 theme C-terminal 647:656 arg1 region 658:663 a larger C-terminal region 638:663 a larger C-terminal region 638:663 The vFGF of Group II alphabaculovirus is structurally different from that of Group I alphabaculovirus, with a larger C-terminal region and additional N-linked glycosylation sites. 27142667 8 57 theme lethal 1340:1345 arg1 time 1347:1350 the median lethal time 1329:1350 the median lethal time 1329:1350 However, bioassays showed that HearNPV vfgf deletion significantly increased the median lethal dose and delayed the median lethal time by ∼12 h in the host insect when the virus was delivered orally. 27142667 0 58 theme factor 48:53 arg1 homolog 55:61 the viral fibroblast growth factor homolog 20:61 the viral fibroblast growth factor homolog of Helicoverpa armigera single nucleopolyhedrovirus 20:113 Characterization of the viral fibroblast growth factor homolog of Helicoverpa armigera single nucleopolyhedrovirus. 27142667 3 59 theme glycosylation 689:701 arg1 sites 703:707 additional N-linked glycosylation sites 669:707 additional N-linked glycosylation sites 669:707 The vFGF of Group II alphabaculovirus is structurally different from that of Group I alphabaculovirus, with a larger C-terminal region and additional N-linked glycosylation sites. 27142667 5 60 theme HearNPV-infected 928:943 arg1 cells 945:949 HearNPV-infected cells 928:949 HearNPV-infected cells 928:949 The transcription and expression of vfgf was detected at 3 h and 16 h post-infection in HearNPV-infected cells. 27142667 3 61 with different 584:592 arg1 region 658:663 a larger C-terminal region 638:663 a larger C-terminal region 638:663 The vFGF of Group II alphabaculovirus is structurally different from that of Group I alphabaculovirus, with a larger C-terminal region and additional N-linked glycosylation sites. 27142667 3 61 with different 584:592 arg1 sites 703:707 additional N-linked glycosylation sites 669:707 additional N-linked glycosylation sites 669:707 The vFGF of Group II alphabaculovirus is structurally different from that of Group I alphabaculovirus, with a larger C-terminal region and additional N-linked glycosylation sites. 27142667 2 62 theme I 325:325 arg1 alphabaculoviruses 327:344 Group I alphabaculoviruses 319:344 Group I alphabaculoviruses 319:344 The function of vFGFs from Group I alphabaculoviruses, including Autographa californica multiple nucleopolyhedrovirus (AcMNPV) and Bombyx mori nucleopolyhedrovirus (BmNPV), involves accelerated killing of infected larvae by both viruses. 27142667 2 62 theme I 325:325 arg1 nucleopolyhedrovirus 389:408 Autographa californica multiple nucleopolyhedrovirus 357:408 Autographa californica multiple nucleopolyhedrovirus (AcMNPV) 357:417 The function of vFGFs from Group I alphabaculoviruses, including Autographa californica multiple nucleopolyhedrovirus (AcMNPV) and Bombyx mori nucleopolyhedrovirus (BmNPV), involves accelerated killing of infected larvae by both viruses. 27142667 2 62 theme I 325:325 arg1 nucleopolyhedrovirus 435:454 Bombyx mori nucleopolyhedrovirus 423:454 Bombyx mori nucleopolyhedrovirus (BmNPV) 423:462 The function of vFGFs from Group I alphabaculoviruses, including Autographa californica multiple nucleopolyhedrovirus (AcMNPV) and Bombyx mori nucleopolyhedrovirus (BmNPV), involves accelerated killing of infected larvae by both viruses. 27142667 3 63 link N-linked 680:687 arg1 sites 703:707 additional N-linked glycosylation sites 669:707 additional N-linked glycosylation sites 669:707 The vFGF of Group II alphabaculovirus is structurally different from that of Group I alphabaculovirus, with a larger C-terminal region and additional N-linked glycosylation sites. 27142667 4 64 theme armigera 792:799 arg1 HearNPV 830:836 HearNPV 830:836 HearNPV 830:836 In this study, we characterized the Group II alphabaculovirus vFGF of Helicoverpa armigera single nucleopolyhedrovirus (HearNPV). 27142667 4 64 theme armigera 792:799 arg1 nucleopolyhedrovirus 808:827 Helicoverpa armigera single nucleopolyhedrovirus 780:827 Helicoverpa armigera single nucleopolyhedrovirus (HearNPV) 780:837 In this study, we characterized the Group II alphabaculovirus vFGF of Helicoverpa armigera single nucleopolyhedrovirus (HearNPV). 27142667 3 65 theme additional 669:678 arg1 sites 703:707 additional N-linked glycosylation sites 669:707 additional N-linked glycosylation sites 669:707 The vFGF of Group II alphabaculovirus is structurally different from that of Group I alphabaculovirus, with a larger C-terminal region and additional N-linked glycosylation sites. 27142667 4 66 theme nucleopolyhedrovirus 808:827 arg1 vFGF 772:775 the Group II alphabaculovirus vFGF 742:775 the Group II alphabaculovirus vFGF of Helicoverpa armigera single nucleopolyhedrovirus (HearNPV) 742:837 In this study, we characterized the Group II alphabaculovirus vFGF of Helicoverpa armigera single nucleopolyhedrovirus (HearNPV). 27142667 2 67 theme Group 319:323 arg1 alphabaculoviruses 327:344 Group I alphabaculoviruses 319:344 Group I alphabaculoviruses 319:344 The function of vFGFs from Group I alphabaculoviruses, including Autographa californica multiple nucleopolyhedrovirus (AcMNPV) and Bombyx mori nucleopolyhedrovirus (BmNPV), involves accelerated killing of infected larvae by both viruses. 27142667 2 67 theme Group 319:323 arg1 nucleopolyhedrovirus 389:408 Autographa californica multiple nucleopolyhedrovirus 357:408 Autographa californica multiple nucleopolyhedrovirus (AcMNPV) 357:417 The function of vFGFs from Group I alphabaculoviruses, including Autographa californica multiple nucleopolyhedrovirus (AcMNPV) and Bombyx mori nucleopolyhedrovirus (BmNPV), involves accelerated killing of infected larvae by both viruses. 27142667 2 67 theme Group 319:323 arg1 nucleopolyhedrovirus 435:454 Bombyx mori nucleopolyhedrovirus 423:454 Bombyx mori nucleopolyhedrovirus (BmNPV) 423:462 The function of vFGFs from Group I alphabaculoviruses, including Autographa californica multiple nucleopolyhedrovirus (AcMNPV) and Bombyx mori nucleopolyhedrovirus (BmNPV), involves accelerated killing of infected larvae by both viruses. 27142667 7 68 contain had 1126:1128 arg1 Deletion 1109:1116 Deletion 1109:1116 Deletion of vfgf 1109:1124 Deletion of vfgf had no effect on budded-virus production or viral DNA replication in cultured HzAM1 cells. 27142667 7 68 contain had 1126:1128 arg2 effect 1133:1138 no effect 1130:1138 no effect 1130:1138 Deletion of vfgf had no effect on budded-virus production or viral DNA replication in cultured HzAM1 cells. 27142667 3 69 gly glycosylation 689:701 arg2 sites 703:707 additional N-linked glycosylation sites 669:707 additional N-linked glycosylation sites 669:707 The vFGF of Group II alphabaculovirus is structurally different from that of Group I alphabaculovirus, with a larger C-terminal region and additional N-linked glycosylation sites. 27142667 0 70 theme Helicoverpa 66:76 arg1 nucleopolyhedrovirus 94:113 Helicoverpa armigera single nucleopolyhedrovirus 66:113 Helicoverpa armigera single nucleopolyhedrovirus 66:113 Characterization of the viral fibroblast growth factor homolog of Helicoverpa armigera single nucleopolyhedrovirus. 27142667 3 71 theme N-linked 680:687 arg1 sites 703:707 additional N-linked glycosylation sites 669:707 additional N-linked glycosylation sites 669:707 The vFGF of Group II alphabaculovirus is structurally different from that of Group I alphabaculovirus, with a larger C-terminal region and additional N-linked glycosylation sites. 27142667 6 72 theme cultured 1081:1088 arg1 cells 1090:1094 cultured cells 1081:1094 cultured cells 1081:1094 To further study vFGF function, we constructed vfgf-knockout and -repaired HearNPV bacmids and investigated their affect in both cultured cells and insects. 27142667 2 73 theme multiple 380:387 arg1 AcMNPV 411:416 AcMNPV 411:416 AcMNPV 411:416 The function of vFGFs from Group I alphabaculoviruses, including Autographa californica multiple nucleopolyhedrovirus (AcMNPV) and Bombyx mori nucleopolyhedrovirus (BmNPV), involves accelerated killing of infected larvae by both viruses. 27142667 2 73 theme multiple 380:387 arg1 nucleopolyhedrovirus 389:408 Autographa californica multiple nucleopolyhedrovirus 357:408 Autographa californica multiple nucleopolyhedrovirus (AcMNPV) 357:417 The function of vFGFs from Group I alphabaculoviruses, including Autographa californica multiple nucleopolyhedrovirus (AcMNPV) and Bombyx mori nucleopolyhedrovirus (BmNPV), involves accelerated killing of infected larvae by both viruses. 27142667 8 74 from h 1359:1359 arg1 insect 1373:1378 the host insect 1364:1378 the host insect 1364:1378 However, bioassays showed that HearNPV vfgf deletion significantly increased the median lethal dose and delayed the median lethal time by ∼12 h in the host insect when the virus was delivered orally. 27142667 2 75 theme accelerated 474:484 arg1 killing 486:492 accelerated killing 474:492 accelerated killing of infected larvae by both viruses 474:527 The function of vFGFs from Group I alphabaculoviruses, including Autographa californica multiple nucleopolyhedrovirus (AcMNPV) and Bombyx mori nucleopolyhedrovirus (BmNPV), involves accelerated killing of infected larvae by both viruses. 27142667 7 76 from production 1156:1165 arg1 cells 1210:1214 cultured HzAM1 cells 1195:1214 cultured HzAM1 cells 1195:1214 Deletion of vfgf had no effect on budded-virus production or viral DNA replication in cultured HzAM1 cells. 27142667 2 77 theme californica 368:378 arg1 AcMNPV 411:416 AcMNPV 411:416 AcMNPV 411:416 The function of vFGFs from Group I alphabaculoviruses, including Autographa californica multiple nucleopolyhedrovirus (AcMNPV) and Bombyx mori nucleopolyhedrovirus (BmNPV), involves accelerated killing of infected larvae by both viruses. 27142667 2 77 theme californica 368:378 arg1 nucleopolyhedrovirus 389:408 Autographa californica multiple nucleopolyhedrovirus 357:408 Autographa californica multiple nucleopolyhedrovirus (AcMNPV) 357:417 The function of vFGFs from Group I alphabaculoviruses, including Autographa californica multiple nucleopolyhedrovirus (AcMNPV) and Bombyx mori nucleopolyhedrovirus (BmNPV), involves accelerated killing of infected larvae by both viruses. 26733198 2 0 theme specificity 530:540 arg1 virtue 507:512 virtue 507:512 virtue of the inherent specificity of the glycosyltransferases 507:568 SEEL can circumvent many of the possible issues associated with metabolic labeling, including low incorporation of sugar precursors, and allows for sugars to be added selectively to different types of glycans by virtue of the inherent specificity of the glycosyltransferases. 26733198 4 1 from shift 953:957 arg1 cells 1017:1021 the differentiated cells 998:1021 the differentiated cells 998:1021 Our results show that the profile of glycoproteins detected varies between undifferentiated HEL cells and those differentiated to megakaryocytes, with a shift to more N-linked sialoglycoproteins in the differentiated cells. 26733198 8 2 theme adhesion 1685:1692 arg1 markers 1740:1746 the known megakaryocytic markers 1715:1746 the known megakaryocytic markers integrinβ3 and CD44 1715:1766 Furthermore, this analysis enabled the identification of increased surface expression of several sialylated cell adhesion molecules, including the known megakaryocytic markers integrinβ3 and CD44, upon differentiation of HEL cells to adherent megakaryocytes. 26733198 8 2 theme adhesion 1685:1692 arg1 molecules 1694:1702 several sialylated cell adhesion molecules 1661:1702 several sialylated cell adhesion molecules 1661:1702 Furthermore, this analysis enabled the identification of increased surface expression of several sialylated cell adhesion molecules, including the known megakaryocytic markers integrinβ3 and CD44, upon differentiation of HEL cells to adherent megakaryocytes. 26733198 2 3 theme precursors 416:425 arg1 incorporation 393:405 low incorporation 389:405 low incorporation of sugar precursors 389:425 SEEL can circumvent many of the possible issues associated with metabolic labeling, including low incorporation of sugar precursors, and allows for sugars to be added selectively to different types of glycans by virtue of the inherent specificity of the glycosyltransferases. 26733198 8 4 theme cell 1680:1683 arg1 markers 1740:1746 the known megakaryocytic markers 1715:1746 the known megakaryocytic markers integrinβ3 and CD44 1715:1766 Furthermore, this analysis enabled the identification of increased surface expression of several sialylated cell adhesion molecules, including the known megakaryocytic markers integrinβ3 and CD44, upon differentiation of HEL cells to adherent megakaryocytes. 26733198 8 4 theme cell 1680:1683 arg1 molecules 1694:1702 several sialylated cell adhesion molecules 1661:1702 several sialylated cell adhesion molecules 1661:1702 Furthermore, this analysis enabled the identification of increased surface expression of several sialylated cell adhesion molecules, including the known megakaryocytic markers integrinβ3 and CD44, upon differentiation of HEL cells to adherent megakaryocytes. 26733198 8 5 theme HEL 1793:1795 arg1 cells 1797:1801 HEL cells 1793:1801 HEL cells 1793:1801 Furthermore, this analysis enabled the identification of increased surface expression of several sialylated cell adhesion molecules, including the known megakaryocytic markers integrinβ3 and CD44, upon differentiation of HEL cells to adherent megakaryocytes. 26733198 0 6 theme Megakaryocytic 98:111 arg1 Differentiation 113:127 Megakaryocytic Differentiation 98:127 Megakaryocytic Differentiation 98:127 Selective Exo-Enzymatic Labeling Detects Increased Cell Surface Sialoglycoprotein Expression upon Megakaryocytic Differentiation. 26733198 8 7 theme several 1661:1667 arg1 markers 1740:1746 the known megakaryocytic markers 1715:1746 the known megakaryocytic markers integrinβ3 and CD44 1715:1766 Furthermore, this analysis enabled the identification of increased surface expression of several sialylated cell adhesion molecules, including the known megakaryocytic markers integrinβ3 and CD44, upon differentiation of HEL cells to adherent megakaryocytes. 26733198 8 7 theme several 1661:1667 arg1 molecules 1694:1702 several sialylated cell adhesion molecules 1661:1702 several sialylated cell adhesion molecules 1661:1702 Furthermore, this analysis enabled the identification of increased surface expression of several sialylated cell adhesion molecules, including the known megakaryocytic markers integrinβ3 and CD44, upon differentiation of HEL cells to adherent megakaryocytes. 26733198 7 8 gly glycoproteins 1438:1450 arg1 glycoproteins 1438:1450 many glycoproteins 1433:1450 many glycoproteins 1433:1450 The proteomic findings demonstrated that the detection of many glycoproteins is markedly improved by SEEL labeling, and that unique glycoproteins can be identified using either ST6Gal1 or ST3Gal1. 26733198 2 9 theme sugar 410:414 arg1 precursors 416:425 sugar precursors 410:425 sugar precursors 410:425 SEEL can circumvent many of the possible issues associated with metabolic labeling, including low incorporation of sugar precursors, and allows for sugars to be added selectively to different types of glycans by virtue of the inherent specificity of the glycosyltransferases. 26733198 4 10 gly glycoproteins 837:849 arg1 glycoproteins 837:849 glycoproteins 837:849 glycoproteins detected 837:858 Our results show that the profile of glycoproteins detected varies between undifferentiated HEL cells and those differentiated to megakaryocytes, with a shift to more N-linked sialoglycoproteins in the differentiated cells. 26733198 5 11 theme prior 1115:1119 arg1 treatment 1135:1143 prior neuraminidase treatment 1115:1143 prior neuraminidase treatment highlighting the necessity for the presence of available acceptors with this labeling method 1115:1236 The efficiency of SEEL for both sialyltransferases in HEL cells was greatly increased with prior neuraminidase treatment highlighting the necessity for the presence of available acceptors with this labeling method. 26733198 6 12 theme metabolic 1249:1257 arg1 labeling 1259:1266 metabolic labeling 1249:1266 metabolic labeling 1249:1266 Following metabolic labeling or SEEL, tagged glycoproteins were enriched by immunoprecipitation and identified using mass spectrometry. 26733198 5 13 theme available 1192:1200 arg1 acceptors 1202:1210 available acceptors 1192:1210 available acceptors with this labeling method 1192:1236 The efficiency of SEEL for both sialyltransferases in HEL cells was greatly increased with prior neuraminidase treatment highlighting the necessity for the presence of available acceptors with this labeling method. 26733198 3 14 theme sialoglycoproteins 603:620 arg1 labeling 591:598 the labeling 587:598 the labeling of sialoglycoproteins 587:620 Here we compare the labeling of sialoglycoproteins in undifferentiated and differentiated human erythroleukemia cells (HEL) using SEEL using the sialyltransferases ST6Gal1 and ST3Gal1, which label N- and O-glycans, respectively. 26733198 2 15 theme issues 336:341 arg1 issues 336:341 the possible issues 323:341 the possible issues associated with metabolic labeling 323:376 SEEL can circumvent many of the possible issues associated with metabolic labeling, including low incorporation of sugar precursors, and allows for sugars to be added selectively to different types of glycans by virtue of the inherent specificity of the glycosyltransferases. 26733198 2 15 theme issues 336:341 arg1 many 315:318 many 315:318 many 315:318 SEEL can circumvent many of the possible issues associated with metabolic labeling, including low incorporation of sugar precursors, and allows for sugars to be added selectively to different types of glycans by virtue of the inherent specificity of the glycosyltransferases. 26733198 8 16 theme cells 1797:1801 arg1 differentiation 1774:1788 differentiation 1774:1788 differentiation of HEL cells to adherent megakaryocytes 1774:1828 Furthermore, this analysis enabled the identification of increased surface expression of several sialylated cell adhesion molecules, including the known megakaryocytic markers integrinβ3 and CD44, upon differentiation of HEL cells to adherent megakaryocytes. 26733198 4 17 link N-linked 967:974 arg1 sialoglycoproteins 976:993 more N-linked sialoglycoproteins 962:993 more N-linked sialoglycoproteins 962:993 Our results show that the profile of glycoproteins detected varies between undifferentiated HEL cells and those differentiated to megakaryocytes, with a shift to more N-linked sialoglycoproteins in the differentiated cells. 26733198 5 18 theme acceptors 1202:1210 arg1 presence 1180:1187 the presence 1176:1187 the presence of available acceptors with this labeling method 1176:1236 The efficiency of SEEL for both sialyltransferases in HEL cells was greatly increased with prior neuraminidase treatment highlighting the necessity for the presence of available acceptors with this labeling method. 26733198 2 19 theme possible 327:334 arg1 issues 336:341 the possible issues 323:341 the possible issues associated with metabolic labeling 323:376 SEEL can circumvent many of the possible issues associated with metabolic labeling, including low incorporation of sugar precursors, and allows for sugars to be added selectively to different types of glycans by virtue of the inherent specificity of the glycosyltransferases. 26733198 1 20 theme nucleotide-sugar 215:230 arg1 analogues 232:240 nucleotide-sugar analogues 215:240 nucleotide-sugar analogues 215:240 Selective exo-enzymatic labeling (or SEEL) uses recombinant glycosyltransferases and nucleotide-sugar analogues to allow efficient labeling of cell surface glycans. 26733198 2 21 theme glycosyltransferases 549:568 arg1 specificity 530:540 the inherent specificity 517:540 the inherent specificity of the glycosyltransferases 517:568 SEEL can circumvent many of the possible issues associated with metabolic labeling, including low incorporation of sugar precursors, and allows for sugars to be added selectively to different types of glycans by virtue of the inherent specificity of the glycosyltransferases. 26733198 8 22 theme molecules 1694:1702 arg1 expression 1647:1656 increased surface expression 1629:1656 increased surface expression of several sialylated cell adhesion molecules, including the known megakaryocytic markers integrinβ3 and CD44 1629:1766 Furthermore, this analysis enabled the identification of increased surface expression of several sialylated cell adhesion molecules, including the known megakaryocytic markers integrinβ3 and CD44, upon differentiation of HEL cells to adherent megakaryocytes. 26733198 6 23 gly glycoproteins 1284:1296 arg1 glycoproteins 1284:1296 tagged glycoproteins 1277:1296 tagged glycoproteins 1277:1296 Following metabolic labeling or SEEL, tagged glycoproteins were enriched by immunoprecipitation and identified using mass spectrometry. 26733198 2 24 theme glycans 496:502 arg1 types 487:491 different types 477:491 different types of glycans 477:502 SEEL can circumvent many of the possible issues associated with metabolic labeling, including low incorporation of sugar precursors, and allows for sugars to be added selectively to different types of glycans by virtue of the inherent specificity of the glycosyltransferases. 26733198 7 25 theme SEEL 1476:1479 arg1 labeling 1481:1488 SEEL labeling 1476:1488 SEEL labeling 1476:1488 The proteomic findings demonstrated that the detection of many glycoproteins is markedly improved by SEEL labeling, and that unique glycoproteins can be identified using either ST6Gal1 or ST3Gal1. 26733198 0 26 theme Exo-Enzymatic 10:22 arg1 Labeling 24:31 Selective Exo-Enzymatic Labeling 0:31 Selective Exo-Enzymatic Labeling 0:31 Selective Exo-Enzymatic Labeling Detects Increased Cell Surface Sialoglycoprotein Expression upon Megakaryocytic Differentiation. 26733198 2 27 theme inherent 521:528 arg1 specificity 530:540 the inherent specificity 517:540 the inherent specificity of the glycosyltransferases 517:568 SEEL can circumvent many of the possible issues associated with metabolic labeling, including low incorporation of sugar precursors, and allows for sugars to be added selectively to different types of glycans by virtue of the inherent specificity of the glycosyltransferases. 26733198 3 28 theme undifferentiated 625:640 arg1 HEL 690:692 HEL 690:692 HEL 690:692 Here we compare the labeling of sialoglycoproteins in undifferentiated and differentiated human erythroleukemia cells (HEL) using SEEL using the sialyltransferases ST6Gal1 and ST3Gal1, which label N- and O-glycans, respectively. 26733198 3 28 theme undifferentiated 625:640 arg1 cells 683:687 undifferentiated and differentiated human erythroleukemia cells 625:687 undifferentiated and differentiated human erythroleukemia cells (HEL) 625:693 Here we compare the labeling of sialoglycoproteins in undifferentiated and differentiated human erythroleukemia cells (HEL) using SEEL using the sialyltransferases ST6Gal1 and ST3Gal1, which label N- and O-glycans, respectively. 26733198 8 29 theme sialylated 1669:1678 arg1 markers 1740:1746 the known megakaryocytic markers 1715:1746 the known megakaryocytic markers integrinβ3 and CD44 1715:1766 Furthermore, this analysis enabled the identification of increased surface expression of several sialylated cell adhesion molecules, including the known megakaryocytic markers integrinβ3 and CD44, upon differentiation of HEL cells to adherent megakaryocytes. 26733198 8 29 theme sialylated 1669:1678 arg1 molecules 1694:1702 several sialylated cell adhesion molecules 1661:1702 several sialylated cell adhesion molecules 1661:1702 Furthermore, this analysis enabled the identification of increased surface expression of several sialylated cell adhesion molecules, including the known megakaryocytic markers integrinβ3 and CD44, upon differentiation of HEL cells to adherent megakaryocytes. 26733198 0 30 theme Selective 0:8 arg1 Labeling 24:31 Selective Exo-Enzymatic Labeling 0:31 Selective Exo-Enzymatic Labeling 0:31 Selective Exo-Enzymatic Labeling Detects Increased Cell Surface Sialoglycoprotein Expression upon Megakaryocytic Differentiation. 26733198 1 31 theme Selective 130:138 arg1 SEEL 167:170 SEEL 167:170 SEEL 167:170 Selective exo-enzymatic labeling (or SEEL) uses recombinant glycosyltransferases and nucleotide-sugar analogues to allow efficient labeling of cell surface glycans. 26733198 1 31 theme Selective 130:138 arg1 labeling 154:161 Selective exo-enzymatic labeling 130:161 Selective exo-enzymatic labeling (or SEEL) 130:171 Selective exo-enzymatic labeling (or SEEL) uses recombinant glycosyltransferases and nucleotide-sugar analogues to allow efficient labeling of cell surface glycans. 26733198 7 32 theme unique 1500:1505 arg1 glycoproteins 1507:1519 unique glycoproteins 1500:1519 unique glycoproteins 1500:1519 The proteomic findings demonstrated that the detection of many glycoproteins is markedly improved by SEEL labeling, and that unique glycoproteins can be identified using either ST6Gal1 or ST3Gal1. 26733198 4 33 theme differentiated 1002:1015 arg1 cells 1017:1021 the differentiated cells 998:1021 the differentiated cells 998:1021 Our results show that the profile of glycoproteins detected varies between undifferentiated HEL cells and those differentiated to megakaryocytes, with a shift to more N-linked sialoglycoproteins in the differentiated cells. 26733198 5 34 theme neuraminidase 1121:1133 arg1 treatment 1135:1143 prior neuraminidase treatment 1115:1143 prior neuraminidase treatment highlighting the necessity for the presence of available acceptors with this labeling method 1115:1236 The efficiency of SEEL for both sialyltransferases in HEL cells was greatly increased with prior neuraminidase treatment highlighting the necessity for the presence of available acceptors with this labeling method. 26733198 1 35 theme exo-enzymatic 140:152 arg1 SEEL 167:170 SEEL 167:170 SEEL 167:170 Selective exo-enzymatic labeling (or SEEL) uses recombinant glycosyltransferases and nucleotide-sugar analogues to allow efficient labeling of cell surface glycans. 26733198 1 35 theme exo-enzymatic 140:152 arg1 labeling 154:161 Selective exo-enzymatic labeling 130:161 Selective exo-enzymatic labeling (or SEEL) 130:171 Selective exo-enzymatic labeling (or SEEL) uses recombinant glycosyltransferases and nucleotide-sugar analogues to allow efficient labeling of cell surface glycans. 26733198 8 36 theme expression 1647:1656 arg1 identification 1611:1624 the identification 1607:1624 the identification of increased surface expression of several sialylated cell adhesion molecules, including the known megakaryocytic markers integrinβ3 and CD44 1607:1766 Furthermore, this analysis enabled the identification of increased surface expression of several sialylated cell adhesion molecules, including the known megakaryocytic markers integrinβ3 and CD44, upon differentiation of HEL cells to adherent megakaryocytes. 26733198 1 37 theme efficient 251:259 arg1 labeling 261:268 efficient labeling 251:268 efficient labeling of cell surface glycans 251:292 Selective exo-enzymatic labeling (or SEEL) uses recombinant glycosyltransferases and nucleotide-sugar analogues to allow efficient labeling of cell surface glycans. 26733198 2 38 theme different 477:485 arg1 types 487:491 different types 477:491 different types of glycans 477:502 SEEL can circumvent many of the possible issues associated with metabolic labeling, including low incorporation of sugar precursors, and allows for sugars to be added selectively to different types of glycans by virtue of the inherent specificity of the glycosyltransferases. 26733198 8 39 theme known 1719:1723 arg1 markers 1740:1746 the known megakaryocytic markers 1715:1746 the known megakaryocytic markers integrinβ3 and CD44 1715:1766 Furthermore, this analysis enabled the identification of increased surface expression of several sialylated cell adhesion molecules, including the known megakaryocytic markers integrinβ3 and CD44, upon differentiation of HEL cells to adherent megakaryocytes. 26733198 8 39 theme known 1719:1723 arg1 CD44 1763:1766 CD44 1763:1766 CD44 1763:1766 Furthermore, this analysis enabled the identification of increased surface expression of several sialylated cell adhesion molecules, including the known megakaryocytic markers integrinβ3 and CD44, upon differentiation of HEL cells to adherent megakaryocytes. 26733198 8 39 theme known 1719:1723 arg1 integrinβ3 1748:1757 integrinβ3 1748:1757 integrinβ3 1748:1757 Furthermore, this analysis enabled the identification of increased surface expression of several sialylated cell adhesion molecules, including the known megakaryocytic markers integrinβ3 and CD44, upon differentiation of HEL cells to adherent megakaryocytes. 26733198 4 40 theme glycoproteins 837:849 arg1 profile 826:832 the profile 822:832 the profile of glycoproteins detected 822:858 Our results show that the profile of glycoproteins detected varies between undifferentiated HEL cells and those differentiated to megakaryocytes, with a shift to more N-linked sialoglycoproteins in the differentiated cells. 26733198 5 41 theme SEEL 1042:1045 arg1 efficiency 1028:1037 The efficiency 1024:1037 The efficiency of SEEL for both sialyltransferases in HEL cells 1024:1086 The efficiency of SEEL for both sialyltransferases in HEL cells was greatly increased with prior neuraminidase treatment highlighting the necessity for the presence of available acceptors with this labeling method. 26733198 8 42 gly sialylated 1669:1678 arg1 markers 1740:1746 the known megakaryocytic markers 1715:1746 the known megakaryocytic markers integrinβ3 and CD44 1715:1766 Furthermore, this analysis enabled the identification of increased surface expression of several sialylated cell adhesion molecules, including the known megakaryocytic markers integrinβ3 and CD44, upon differentiation of HEL cells to adherent megakaryocytes. 26733198 8 42 gly sialylated 1669:1678 arg1 molecules 1694:1702 several sialylated cell adhesion molecules 1661:1702 several sialylated cell adhesion molecules 1661:1702 Furthermore, this analysis enabled the identification of increased surface expression of several sialylated cell adhesion molecules, including the known megakaryocytic markers integrinβ3 and CD44, upon differentiation of HEL cells to adherent megakaryocytes. 26733198 0 43 theme Cell 51:54 arg1 Expression 82:91 Increased Cell Surface Sialoglycoprotein Expression 41:91 Increased Cell Surface Sialoglycoprotein Expression 41:91 Selective Exo-Enzymatic Labeling Detects Increased Cell Surface Sialoglycoprotein Expression upon Megakaryocytic Differentiation. 26733198 3 44 theme erythroleukemia 667:681 arg1 HEL 690:692 HEL 690:692 HEL 690:692 Here we compare the labeling of sialoglycoproteins in undifferentiated and differentiated human erythroleukemia cells (HEL) using SEEL using the sialyltransferases ST6Gal1 and ST3Gal1, which label N- and O-glycans, respectively. 26733198 3 44 theme erythroleukemia 667:681 arg1 cells 683:687 undifferentiated and differentiated human erythroleukemia cells 625:687 undifferentiated and differentiated human erythroleukemia cells (HEL) 625:693 Here we compare the labeling of sialoglycoproteins in undifferentiated and differentiated human erythroleukemia cells (HEL) using SEEL using the sialyltransferases ST6Gal1 and ST3Gal1, which label N- and O-glycans, respectively. 26733198 0 45 theme Increased 41:49 arg1 Expression 82:91 Increased Cell Surface Sialoglycoprotein Expression 41:91 Increased Cell Surface Sialoglycoprotein Expression 41:91 Selective Exo-Enzymatic Labeling Detects Increased Cell Surface Sialoglycoprotein Expression upon Megakaryocytic Differentiation. 26733198 8 46 dep markers 1740:1746 arg1 markers 1740:1746 the known megakaryocytic markers 1715:1746 the known megakaryocytic markers integrinβ3 and CD44 1715:1766 Furthermore, this analysis enabled the identification of increased surface expression of several sialylated cell adhesion molecules, including the known megakaryocytic markers integrinβ3 and CD44, upon differentiation of HEL cells to adherent megakaryocytes. 26733198 8 46 dep markers 1740:1746 arg1 CD44 1763:1766 CD44 1763:1766 CD44 1763:1766 Furthermore, this analysis enabled the identification of increased surface expression of several sialylated cell adhesion molecules, including the known megakaryocytic markers integrinβ3 and CD44, upon differentiation of HEL cells to adherent megakaryocytes. 26733198 8 46 dep markers 1740:1746 arg1 integrinβ3 1748:1757 integrinβ3 1748:1757 integrinβ3 1748:1757 Furthermore, this analysis enabled the identification of increased surface expression of several sialylated cell adhesion molecules, including the known megakaryocytic markers integrinβ3 and CD44, upon differentiation of HEL cells to adherent megakaryocytes. 26733198 4 47 theme HEL 892:894 arg1 cells 896:900 undifferentiated HEL cells 875:900 undifferentiated HEL cells 875:900 Our results show that the profile of glycoproteins detected varies between undifferentiated HEL cells and those differentiated to megakaryocytes, with a shift to more N-linked sialoglycoproteins in the differentiated cells. 26733198 1 48 theme cell 273:276 arg1 glycans 286:292 cell surface glycans 273:292 cell surface glycans 273:292 Selective exo-enzymatic labeling (or SEEL) uses recombinant glycosyltransferases and nucleotide-sugar analogues to allow efficient labeling of cell surface glycans. 26733198 0 49 theme Sialoglycoprotein 64:80 arg1 Expression 82:91 Increased Cell Surface Sialoglycoprotein Expression 41:91 Increased Cell Surface Sialoglycoprotein Expression 41:91 Selective Exo-Enzymatic Labeling Detects Increased Cell Surface Sialoglycoprotein Expression upon Megakaryocytic Differentiation. 26733198 8 50 theme megakaryocytic 1725:1738 arg1 markers 1740:1746 the known megakaryocytic markers 1715:1746 the known megakaryocytic markers integrinβ3 and CD44 1715:1766 Furthermore, this analysis enabled the identification of increased surface expression of several sialylated cell adhesion molecules, including the known megakaryocytic markers integrinβ3 and CD44, upon differentiation of HEL cells to adherent megakaryocytes. 26733198 8 50 theme megakaryocytic 1725:1738 arg1 CD44 1763:1766 CD44 1763:1766 CD44 1763:1766 Furthermore, this analysis enabled the identification of increased surface expression of several sialylated cell adhesion molecules, including the known megakaryocytic markers integrinβ3 and CD44, upon differentiation of HEL cells to adherent megakaryocytes. 26733198 8 50 theme megakaryocytic 1725:1738 arg1 integrinβ3 1748:1757 integrinβ3 1748:1757 integrinβ3 1748:1757 Furthermore, this analysis enabled the identification of increased surface expression of several sialylated cell adhesion molecules, including the known megakaryocytic markers integrinβ3 and CD44, upon differentiation of HEL cells to adherent megakaryocytes. 26733198 4 51 theme N-linked 967:974 arg1 sialoglycoproteins 976:993 more N-linked sialoglycoproteins 962:993 more N-linked sialoglycoproteins 962:993 Our results show that the profile of glycoproteins detected varies between undifferentiated HEL cells and those differentiated to megakaryocytes, with a shift to more N-linked sialoglycoproteins in the differentiated cells. 26733198 3 52 theme differentiated 646:659 arg1 HEL 690:692 HEL 690:692 HEL 690:692 Here we compare the labeling of sialoglycoproteins in undifferentiated and differentiated human erythroleukemia cells (HEL) using SEEL using the sialyltransferases ST6Gal1 and ST3Gal1, which label N- and O-glycans, respectively. 26733198 3 52 theme differentiated 646:659 arg1 cells 683:687 undifferentiated and differentiated human erythroleukemia cells 625:687 undifferentiated and differentiated human erythroleukemia cells (HEL) 625:693 Here we compare the labeling of sialoglycoproteins in undifferentiated and differentiated human erythroleukemia cells (HEL) using SEEL using the sialyltransferases ST6Gal1 and ST3Gal1, which label N- and O-glycans, respectively. 26733198 0 53 theme Surface 56:62 arg1 Expression 82:91 Increased Cell Surface Sialoglycoprotein Expression 41:91 Increased Cell Surface Sialoglycoprotein Expression 41:91 Selective Exo-Enzymatic Labeling Detects Increased Cell Surface Sialoglycoprotein Expression upon Megakaryocytic Differentiation. 26733198 5 54 theme labeling 1222:1229 arg1 method 1231:1236 this labeling method 1217:1236 this labeling method 1217:1236 The efficiency of SEEL for both sialyltransferases in HEL cells was greatly increased with prior neuraminidase treatment highlighting the necessity for the presence of available acceptors with this labeling method. 26733198 3 55 theme human 661:665 arg1 HEL 690:692 HEL 690:692 HEL 690:692 Here we compare the labeling of sialoglycoproteins in undifferentiated and differentiated human erythroleukemia cells (HEL) using SEEL using the sialyltransferases ST6Gal1 and ST3Gal1, which label N- and O-glycans, respectively. 26733198 3 55 theme human 661:665 arg1 cells 683:687 undifferentiated and differentiated human erythroleukemia cells 625:687 undifferentiated and differentiated human erythroleukemia cells (HEL) 625:693 Here we compare the labeling of sialoglycoproteins in undifferentiated and differentiated human erythroleukemia cells (HEL) using SEEL using the sialyltransferases ST6Gal1 and ST3Gal1, which label N- and O-glycans, respectively. 26733198 8 56 theme adherent 1806:1813 arg1 megakaryocytes 1815:1828 adherent megakaryocytes 1806:1828 adherent megakaryocytes 1806:1828 Furthermore, this analysis enabled the identification of increased surface expression of several sialylated cell adhesion molecules, including the known megakaryocytic markers integrinβ3 and CD44, upon differentiation of HEL cells to adherent megakaryocytes. 26733198 6 57 theme tagged 1277:1282 arg1 glycoproteins 1284:1296 tagged glycoproteins 1277:1296 tagged glycoproteins 1277:1296 Following metabolic labeling or SEEL, tagged glycoproteins were enriched by immunoprecipitation and identified using mass spectrometry. 26733198 5 58 theme HEL 1078:1080 arg1 cells 1082:1086 HEL cells 1078:1086 HEL cells 1078:1086 The efficiency of SEEL for both sialyltransferases in HEL cells was greatly increased with prior neuraminidase treatment highlighting the necessity for the presence of available acceptors with this labeling method. 26733198 6 59 theme mass 1356:1359 arg1 spectrometry 1361:1372 mass spectrometry 1356:1372 mass spectrometry 1356:1372 Following metabolic labeling or SEEL, tagged glycoproteins were enriched by immunoprecipitation and identified using mass spectrometry. 26733198 2 60 theme low 389:391 arg1 incorporation 393:405 low incorporation 389:405 low incorporation of sugar precursors 389:425 SEEL can circumvent many of the possible issues associated with metabolic labeling, including low incorporation of sugar precursors, and allows for sugars to be added selectively to different types of glycans by virtue of the inherent specificity of the glycosyltransferases. 26733198 2 61 theme metabolic 359:367 arg1 labeling 369:376 metabolic labeling 359:376 metabolic labeling 359:376 SEEL can circumvent many of the possible issues associated with metabolic labeling, including low incorporation of sugar precursors, and allows for sugars to be added selectively to different types of glycans by virtue of the inherent specificity of the glycosyltransferases. 26733198 1 62 theme surface 278:284 arg1 glycans 286:292 cell surface glycans 273:292 cell surface glycans 273:292 Selective exo-enzymatic labeling (or SEEL) uses recombinant glycosyltransferases and nucleotide-sugar analogues to allow efficient labeling of cell surface glycans. 26733198 8 63 theme increased 1629:1637 arg1 expression 1647:1656 increased surface expression 1629:1656 increased surface expression of several sialylated cell adhesion molecules, including the known megakaryocytic markers integrinβ3 and CD44 1629:1766 Furthermore, this analysis enabled the identification of increased surface expression of several sialylated cell adhesion molecules, including the known megakaryocytic markers integrinβ3 and CD44, upon differentiation of HEL cells to adherent megakaryocytes. 26733198 8 64 theme surface 1639:1645 arg1 expression 1647:1656 increased surface expression 1629:1656 increased surface expression of several sialylated cell adhesion molecules, including the known megakaryocytic markers integrinβ3 and CD44 1629:1766 Furthermore, this analysis enabled the identification of increased surface expression of several sialylated cell adhesion molecules, including the known megakaryocytic markers integrinβ3 and CD44, upon differentiation of HEL cells to adherent megakaryocytes. 26733198 3 65 gly sialoglycoproteins 603:620 arg1 sialoglycoproteins 603:620 sialoglycoproteins 603:620 sialoglycoproteins 603:620 Here we compare the labeling of sialoglycoproteins in undifferentiated and differentiated human erythroleukemia cells (HEL) using SEEL using the sialyltransferases ST6Gal1 and ST3Gal1, which label N- and O-glycans, respectively. 26733198 1 66 theme glycans 286:292 arg1 labeling 261:268 efficient labeling 251:268 efficient labeling of cell surface glycans 251:292 Selective exo-enzymatic labeling (or SEEL) uses recombinant glycosyltransferases and nucleotide-sugar analogues to allow efficient labeling of cell surface glycans. 26733198 7 67 theme many 1433:1436 arg1 glycoproteins 1438:1450 many glycoproteins 1433:1450 many glycoproteins 1433:1450 The proteomic findings demonstrated that the detection of many glycoproteins is markedly improved by SEEL labeling, and that unique glycoproteins can be identified using either ST6Gal1 or ST3Gal1. 26733198 4 68 theme undifferentiated 875:890 arg1 cells 896:900 undifferentiated HEL cells 875:900 undifferentiated HEL cells 875:900 Our results show that the profile of glycoproteins detected varies between undifferentiated HEL cells and those differentiated to megakaryocytes, with a shift to more N-linked sialoglycoproteins in the differentiated cells. 26733198 7 69 theme glycoproteins 1438:1450 arg1 detection 1420:1428 the detection 1416:1428 the detection of many glycoproteins 1416:1450 The proteomic findings demonstrated that the detection of many glycoproteins is markedly improved by SEEL labeling, and that unique glycoproteins can be identified using either ST6Gal1 or ST3Gal1. 26733198 7 70 theme proteomic 1379:1387 arg1 findings 1389:1396 The proteomic findings 1375:1396 The proteomic findings 1375:1396 The proteomic findings demonstrated that the detection of many glycoproteins is markedly improved by SEEL labeling, and that unique glycoproteins can be identified using either ST6Gal1 or ST3Gal1. 26733198 5 71 with acceptors 1202:1210 arg1 method 1231:1236 this labeling method 1217:1236 this labeling method 1217:1236 The efficiency of SEEL for both sialyltransferases in HEL cells was greatly increased with prior neuraminidase treatment highlighting the necessity for the presence of available acceptors with this labeling method. 26733198 7 72 gly glycoproteins 1507:1519 arg1 glycoproteins 1507:1519 unique glycoproteins 1500:1519 unique glycoproteins 1500:1519 The proteomic findings demonstrated that the detection of many glycoproteins is markedly improved by SEEL labeling, and that unique glycoproteins can be identified using either ST6Gal1 or ST3Gal1. 26733198 4 73 gly sialoglycoproteins 976:993 arg1 sialoglycoproteins 976:993 more N-linked sialoglycoproteins 962:993 more N-linked sialoglycoproteins 962:993 Our results show that the profile of glycoproteins detected varies between undifferentiated HEL cells and those differentiated to megakaryocytes, with a shift to more N-linked sialoglycoproteins in the differentiated cells. 26733198 0 74 gly Sialoglycoprotein 64:80 arg1 Sialoglycoprotein 64:80 Increased Cell Surface Sialoglycoprotein Expression 41:91 Increased Cell Surface Sialoglycoprotein Expression 41:91 Selective Exo-Enzymatic Labeling Detects Increased Cell Surface Sialoglycoprotein Expression upon Megakaryocytic Differentiation. 26733198 1 75 theme recombinant 178:188 arg1 glycosyltransferases 190:209 recombinant glycosyltransferases 178:209 recombinant glycosyltransferases 178:209 Selective exo-enzymatic labeling (or SEEL) uses recombinant glycosyltransferases and nucleotide-sugar analogues to allow efficient labeling of cell surface glycans. 26733198 5 76 from sialyltransferases 1056:1073 arg1 cells 1082:1086 HEL cells 1078:1086 HEL cells 1078:1086 The efficiency of SEEL for both sialyltransferases in HEL cells was greatly increased with prior neuraminidase treatment highlighting the necessity for the presence of available acceptors with this labeling method. 26733198 3 77 dep sialyltransferases 716:733 arg1 sialyltransferases 716:733 the sialyltransferases ST6Gal1 and ST3Gal1 712:753 the sialyltransferases ST6Gal1 and ST3Gal1 712:753 Here we compare the labeling of sialoglycoproteins in undifferentiated and differentiated human erythroleukemia cells (HEL) using SEEL using the sialyltransferases ST6Gal1 and ST3Gal1, which label N- and O-glycans, respectively. 26733198 3 77 dep sialyltransferases 716:733 arg1 ST3Gal1 747:753 ST3Gal1 747:753 ST3Gal1 747:753 Here we compare the labeling of sialoglycoproteins in undifferentiated and differentiated human erythroleukemia cells (HEL) using SEEL using the sialyltransferases ST6Gal1 and ST3Gal1, which label N- and O-glycans, respectively. 26733198 3 77 dep sialyltransferases 716:733 arg1 ST6Gal1 735:741 ST6Gal1 735:741 ST6Gal1 735:741 Here we compare the labeling of sialoglycoproteins in undifferentiated and differentiated human erythroleukemia cells (HEL) using SEEL using the sialyltransferases ST6Gal1 and ST3Gal1, which label N- and O-glycans, respectively. 25068131 0 0 theme extracellular 80:92 arg1 epitopes 94:101 extracellular epitopes 80:101 extracellular epitopes 80:101 A human pluripotent stem cell surface N-glycoproteome resource reveals markers, extracellular epitopes, and drug targets. 25068131 1 1 theme proteins 157:164 arg1 knowledge 131:139 Detailed knowledge 122:139 Detailed knowledge of cell-surface proteins for isolating well-defined populations of human pluripotent stem cells (hPSCs) 122:243 Detailed knowledge of cell-surface proteins for isolating well-defined populations of human pluripotent stem cells (hPSCs) would significantly enhance their characterization and translational potential. 25068131 4 2 theme putative 869:876 arg1 lines 884:888 putative hiPSC lines 869:888 putative hiPSC lines 869:888 The >30 positive and negative markers verified here by orthogonal approaches provide experimental justification for the rational selection of pluripotency and lineage markers, epitopes for cell isolation, and reagents for the characterization of putative hiPSC lines. 25068131 2 3 theme cell-surface 375:386 arg1 inventory 397:405 a cell-surface proteome inventory 373:405 a cell-surface proteome inventory containing 496 N-linked glycoproteins on human embryonic (hESCs) and induced PSCs (hiPSCs) 373:496 Through a chemoproteomic approach, we developed a cell-surface proteome inventory containing 496 N-linked glycoproteins on human embryonic (hESCs) and induced PSCs (hiPSCs). 25068131 5 4 theme GLUT-1 1058:1063 arg1 inhibitor 1065:1073 a reported GLUT-1 inhibitor 1047:1073 a reported GLUT-1 inhibitor 1047:1073 Comparative differences between the chemoproteomic-defined surfaceome and the transcriptome-predicted surfaceome directly led to the discovery that STF-31, a reported GLUT-1 inhibitor, is toxic to hPSCs and efficient for selective elimination of hPSCs from mixed cultures. 25068131 5 4 theme GLUT-1 1058:1063 arg1 STF-31 1039:1044 STF-31 1039:1044 STF-31 1039:1044 Comparative differences between the chemoproteomic-defined surfaceome and the transcriptome-predicted surfaceome directly led to the discovery that STF-31, a reported GLUT-1 inhibitor, is toxic to hPSCs and efficient for selective elimination of hPSCs from mixed cultures. 25068131 3 5 theme types 557:561 arg1 backdrop 509:516 a backdrop 507:516 a backdrop of human fibroblasts and 50 other cell types 507:561 Against a backdrop of human fibroblasts and 50 other cell types, >100 surface proteins of interest for hPSCs were revealed. 25068131 5 6 theme mixed 1148:1152 arg1 cultures 1154:1161 mixed cultures 1148:1161 mixed cultures 1148:1161 Comparative differences between the chemoproteomic-defined surfaceome and the transcriptome-predicted surfaceome directly led to the discovery that STF-31, a reported GLUT-1 inhibitor, is toxic to hPSCs and efficient for selective elimination of hPSCs from mixed cultures. 25068131 4 7 theme markers 790:796 arg1 selection 752:760 the rational selection 739:760 the rational selection of pluripotency and lineage markers, epitopes for cell isolation, and reagents for the characterization of putative hiPSC lines 739:888 The >30 positive and negative markers verified here by orthogonal approaches provide experimental justification for the rational selection of pluripotency and lineage markers, epitopes for cell isolation, and reagents for the characterization of putative hiPSC lines. 25068131 2 8 theme proteome 388:395 arg1 inventory 397:405 a cell-surface proteome inventory 373:405 a cell-surface proteome inventory containing 496 N-linked glycoproteins on human embryonic (hESCs) and induced PSCs (hiPSCs) 373:496 Through a chemoproteomic approach, we developed a cell-surface proteome inventory containing 496 N-linked glycoproteins on human embryonic (hESCs) and induced PSCs (hiPSCs). 25068131 0 9 theme drug 108:111 arg1 targets 113:119 drug targets 108:119 drug targets 108:119 A human pluripotent stem cell surface N-glycoproteome resource reveals markers, extracellular epitopes, and drug targets. 25068131 2 10 gly glycoproteins 431:443 arg1 glycoproteins 431:443 496 N-linked glycoproteins 418:443 496 N-linked glycoproteins on human embryonic (hESCs) and induced PSCs (hiPSCs) 418:496 Through a chemoproteomic approach, we developed a cell-surface proteome inventory containing 496 N-linked glycoproteins on human embryonic (hESCs) and induced PSCs (hiPSCs). 25068131 4 11 theme positive 631:638 arg1 markers 653:659 The >30 positive and negative markers 623:659 The >30 positive and negative markers verified here by orthogonal approaches 623:698 The >30 positive and negative markers verified here by orthogonal approaches provide experimental justification for the rational selection of pluripotency and lineage markers, epitopes for cell isolation, and reagents for the characterization of putative hiPSC lines. 25068131 3 12 theme other 546:550 arg1 types 557:561 50 other cell types 543:561 50 other cell types 543:561 Against a backdrop of human fibroblasts and 50 other cell types, >100 surface proteins of interest for hPSCs were revealed. 25068131 4 13 theme orthogonal 678:687 arg1 approaches 689:698 orthogonal approaches 678:698 orthogonal approaches 678:698 The >30 positive and negative markers verified here by orthogonal approaches provide experimental justification for the rational selection of pluripotency and lineage markers, epitopes for cell isolation, and reagents for the characterization of putative hiPSC lines. 25068131 3 14 theme cell 552:555 arg1 types 557:561 50 other cell types 543:561 50 other cell types 543:561 Against a backdrop of human fibroblasts and 50 other cell types, >100 surface proteins of interest for hPSCs were revealed. 25068131 1 15 theme well-defined 180:191 arg1 populations 193:203 well-defined populations 180:203 well-defined populations of human pluripotent stem cells (hPSCs) 180:243 Detailed knowledge of cell-surface proteins for isolating well-defined populations of human pluripotent stem cells (hPSCs) would significantly enhance their characterization and translational potential. 25068131 0 16 theme human 2:6 arg1 cell 25:28 human pluripotent stem cell 2:28 A human pluripotent stem cell surface N-glycoproteome resource 0:61 A human pluripotent stem cell surface N-glycoproteome resource reveals markers, extracellular epitopes, and drug targets. 25068131 2 17 contain containing 407:416 arg1 inventory 397:405 a cell-surface proteome inventory 373:405 a cell-surface proteome inventory containing 496 N-linked glycoproteins on human embryonic (hESCs) and induced PSCs (hiPSCs) 373:496 Through a chemoproteomic approach, we developed a cell-surface proteome inventory containing 496 N-linked glycoproteins on human embryonic (hESCs) and induced PSCs (hiPSCs). 25068131 2 17 contain containing 407:416 arg2 glycoproteins 431:443 496 N-linked glycoproteins 418:443 496 N-linked glycoproteins on human embryonic (hESCs) and induced PSCs (hiPSCs) 418:496 Through a chemoproteomic approach, we developed a cell-surface proteome inventory containing 496 N-linked glycoproteins on human embryonic (hESCs) and induced PSCs (hiPSCs). 25068131 4 18 theme lines 884:888 arg1 characterization 849:864 the characterization 845:864 the characterization of putative hiPSC lines 845:888 The >30 positive and negative markers verified here by orthogonal approaches provide experimental justification for the rational selection of pluripotency and lineage markers, epitopes for cell isolation, and reagents for the characterization of putative hiPSC lines. 25068131 4 19 theme pluripotency 765:776 arg1 selection 752:760 the rational selection 739:760 the rational selection of pluripotency and lineage markers, epitopes for cell isolation, and reagents for the characterization of putative hiPSC lines 739:888 The >30 positive and negative markers verified here by orthogonal approaches provide experimental justification for the rational selection of pluripotency and lineage markers, epitopes for cell isolation, and reagents for the characterization of putative hiPSC lines. 25068131 2 20 theme N-linked 422:429 arg1 glycoproteins 431:443 496 N-linked glycoproteins 418:443 496 N-linked glycoproteins on human embryonic (hESCs) and induced PSCs (hiPSCs) 418:496 Through a chemoproteomic approach, we developed a cell-surface proteome inventory containing 496 N-linked glycoproteins on human embryonic (hESCs) and induced PSCs (hiPSCs). 25068131 2 21 theme induced 476:482 arg1 hiPSCs 490:495 hiPSCs 490:495 hiPSCs 490:495 Through a chemoproteomic approach, we developed a cell-surface proteome inventory containing 496 N-linked glycoproteins on human embryonic (hESCs) and induced PSCs (hiPSCs). 25068131 2 21 theme induced 476:482 arg1 PSCs 484:487 induced PSCs 476:487 induced PSCs (hiPSCs) 476:496 Through a chemoproteomic approach, we developed a cell-surface proteome inventory containing 496 N-linked glycoproteins on human embryonic (hESCs) and induced PSCs (hiPSCs). 25068131 4 22 theme hiPSC 878:882 arg1 lines 884:888 putative hiPSC lines 869:888 putative hiPSC lines 869:888 The >30 positive and negative markers verified here by orthogonal approaches provide experimental justification for the rational selection of pluripotency and lineage markers, epitopes for cell isolation, and reagents for the characterization of putative hiPSC lines. 25068131 2 23 theme chemoproteomic 335:348 arg1 approach 350:357 a chemoproteomic approach 333:357 a chemoproteomic approach 333:357 Through a chemoproteomic approach, we developed a cell-surface proteome inventory containing 496 N-linked glycoproteins on human embryonic (hESCs) and induced PSCs (hiPSCs). 25068131 4 24 theme experimental 708:719 arg1 justification 721:733 experimental justification 708:733 experimental justification for the rational selection of pluripotency and lineage markers, epitopes for cell isolation, and reagents for the characterization of putative hiPSC lines 708:888 The >30 positive and negative markers verified here by orthogonal approaches provide experimental justification for the rational selection of pluripotency and lineage markers, epitopes for cell isolation, and reagents for the characterization of putative hiPSC lines. 25068131 0 25 theme stem 20:23 arg1 cell 25:28 human pluripotent stem cell 2:28 A human pluripotent stem cell surface N-glycoproteome resource 0:61 A human pluripotent stem cell surface N-glycoproteome resource reveals markers, extracellular epitopes, and drug targets. 25068131 1 26 theme translational 300:312 arg1 potential 314:322 translational potential 300:322 translational potential 300:322 Detailed knowledge of cell-surface proteins for isolating well-defined populations of human pluripotent stem cells (hPSCs) would significantly enhance their characterization and translational potential. 25068131 4 27 theme lineage 782:788 arg1 markers 790:796 lineage markers 782:796 lineage markers 782:796 The >30 positive and negative markers verified here by orthogonal approaches provide experimental justification for the rational selection of pluripotency and lineage markers, epitopes for cell isolation, and reagents for the characterization of putative hiPSC lines. 25068131 1 28 theme human 208:212 arg1 hPSCs 238:242 hPSCs 238:242 hPSCs 238:242 Detailed knowledge of cell-surface proteins for isolating well-defined populations of human pluripotent stem cells (hPSCs) would significantly enhance their characterization and translational potential. 25068131 1 28 theme human 208:212 arg1 cells 231:235 human pluripotent stem cells 208:235 human pluripotent stem cells (hPSCs) 208:243 Detailed knowledge of cell-surface proteins for isolating well-defined populations of human pluripotent stem cells (hPSCs) would significantly enhance their characterization and translational potential. 25068131 0 29 theme pluripotent 8:18 arg1 cell 25:28 human pluripotent stem cell 2:28 A human pluripotent stem cell surface N-glycoproteome resource 0:61 A human pluripotent stem cell surface N-glycoproteome resource reveals markers, extracellular epitopes, and drug targets. 25068131 2 30 link N-linked 422:429 arg1 glycoproteins 431:443 496 N-linked glycoproteins 418:443 496 N-linked glycoproteins on human embryonic (hESCs) and induced PSCs (hiPSCs) 418:496 Through a chemoproteomic approach, we developed a cell-surface proteome inventory containing 496 N-linked glycoproteins on human embryonic (hESCs) and induced PSCs (hiPSCs). 25068131 3 31 theme surface 569:575 arg1 proteins 577:584 >100 surface proteins 564:584 >100 surface proteins of interest for hPSCs 564:606 Against a backdrop of human fibroblasts and 50 other cell types, >100 surface proteins of interest for hPSCs were revealed. 25068131 1 32 theme pluripotent 214:224 arg1 hPSCs 238:242 hPSCs 238:242 hPSCs 238:242 Detailed knowledge of cell-surface proteins for isolating well-defined populations of human pluripotent stem cells (hPSCs) would significantly enhance their characterization and translational potential. 25068131 1 32 theme pluripotent 214:224 arg1 cells 231:235 human pluripotent stem cells 208:235 human pluripotent stem cells (hPSCs) 208:243 Detailed knowledge of cell-surface proteins for isolating well-defined populations of human pluripotent stem cells (hPSCs) would significantly enhance their characterization and translational potential. 25068131 0 33 theme surface 30:36 arg1 resource 54:61 A human pluripotent stem cell surface N-glycoproteome resource 0:61 A human pluripotent stem cell surface N-glycoproteome resource 0:61 A human pluripotent stem cell surface N-glycoproteome resource reveals markers, extracellular epitopes, and drug targets. 25068131 1 34 theme stem 226:229 arg1 hPSCs 238:242 hPSCs 238:242 hPSCs 238:242 Detailed knowledge of cell-surface proteins for isolating well-defined populations of human pluripotent stem cells (hPSCs) would significantly enhance their characterization and translational potential. 25068131 1 34 theme stem 226:229 arg1 cells 231:235 human pluripotent stem cells 208:235 human pluripotent stem cells (hPSCs) 208:243 Detailed knowledge of cell-surface proteins for isolating well-defined populations of human pluripotent stem cells (hPSCs) would significantly enhance their characterization and translational potential. 25068131 0 35 theme cell 25:28 arg1 resource 54:61 A human pluripotent stem cell surface N-glycoproteome resource 0:61 A human pluripotent stem cell surface N-glycoproteome resource 0:61 A human pluripotent stem cell surface N-glycoproteome resource reveals markers, extracellular epitopes, and drug targets. 25068131 5 36 theme hPSCs 1137:1141 arg1 elimination 1122:1132 selective elimination 1112:1132 selective elimination of hPSCs from mixed cultures 1112:1161 Comparative differences between the chemoproteomic-defined surfaceome and the transcriptome-predicted surfaceome directly led to the discovery that STF-31, a reported GLUT-1 inhibitor, is toxic to hPSCs and efficient for selective elimination of hPSCs from mixed cultures. 25068131 1 37 theme cells 231:235 arg1 populations 193:203 well-defined populations 180:203 well-defined populations of human pluripotent stem cells (hPSCs) 180:243 Detailed knowledge of cell-surface proteins for isolating well-defined populations of human pluripotent stem cells (hPSCs) would significantly enhance their characterization and translational potential. 25068131 3 38 theme human 521:525 arg1 fibroblasts 527:537 human fibroblasts 521:537 human fibroblasts 521:537 Against a backdrop of human fibroblasts and 50 other cell types, >100 surface proteins of interest for hPSCs were revealed. 25068131 3 39 theme interest 589:596 arg1 proteins 577:584 >100 surface proteins 564:584 >100 surface proteins of interest for hPSCs 564:606 Against a backdrop of human fibroblasts and 50 other cell types, >100 surface proteins of interest for hPSCs were revealed. 25068131 0 40 theme N-glycoproteome 38:52 arg1 resource 54:61 A human pluripotent stem cell surface N-glycoproteome resource 0:61 A human pluripotent stem cell surface N-glycoproteome resource 0:61 A human pluripotent stem cell surface N-glycoproteome resource reveals markers, extracellular epitopes, and drug targets. 25068131 3 41 theme fibroblasts 527:537 arg1 backdrop 509:516 a backdrop 507:516 a backdrop of human fibroblasts and 50 other cell types 507:561 Against a backdrop of human fibroblasts and 50 other cell types, >100 surface proteins of interest for hPSCs were revealed. 25068131 5 42 theme transcriptome-predicted 969:991 arg1 surfaceome 993:1002 the transcriptome-predicted surfaceome 965:1002 the transcriptome-predicted surfaceome 965:1002 Comparative differences between the chemoproteomic-defined surfaceome and the transcriptome-predicted surfaceome directly led to the discovery that STF-31, a reported GLUT-1 inhibitor, is toxic to hPSCs and efficient for selective elimination of hPSCs from mixed cultures. 25068131 5 43 theme selective 1112:1120 arg1 elimination 1122:1132 selective elimination 1112:1132 selective elimination of hPSCs from mixed cultures 1112:1161 Comparative differences between the chemoproteomic-defined surfaceome and the transcriptome-predicted surfaceome directly led to the discovery that STF-31, a reported GLUT-1 inhibitor, is toxic to hPSCs and efficient for selective elimination of hPSCs from mixed cultures. 25068131 5 44 theme reported 1049:1056 arg1 inhibitor 1065:1073 a reported GLUT-1 inhibitor 1047:1073 a reported GLUT-1 inhibitor 1047:1073 Comparative differences between the chemoproteomic-defined surfaceome and the transcriptome-predicted surfaceome directly led to the discovery that STF-31, a reported GLUT-1 inhibitor, is toxic to hPSCs and efficient for selective elimination of hPSCs from mixed cultures. 25068131 5 44 theme reported 1049:1056 arg1 STF-31 1039:1044 STF-31 1039:1044 STF-31 1039:1044 Comparative differences between the chemoproteomic-defined surfaceome and the transcriptome-predicted surfaceome directly led to the discovery that STF-31, a reported GLUT-1 inhibitor, is toxic to hPSCs and efficient for selective elimination of hPSCs from mixed cultures. 25068131 2 45 from glycoproteins 431:443 arg1 hiPSCs 490:495 hiPSCs 490:495 hiPSCs 490:495 Through a chemoproteomic approach, we developed a cell-surface proteome inventory containing 496 N-linked glycoproteins on human embryonic (hESCs) and induced PSCs (hiPSCs). 25068131 2 45 from glycoproteins 431:443 arg1 embryonic 454:462 embryonic 454:462 embryonic 454:462 Through a chemoproteomic approach, we developed a cell-surface proteome inventory containing 496 N-linked glycoproteins on human embryonic (hESCs) and induced PSCs (hiPSCs). 25068131 2 45 from glycoproteins 431:443 arg1 PSCs 484:487 induced PSCs 476:487 induced PSCs (hiPSCs) 476:496 Through a chemoproteomic approach, we developed a cell-surface proteome inventory containing 496 N-linked glycoproteins on human embryonic (hESCs) and induced PSCs (hiPSCs). 25068131 2 45 from glycoproteins 431:443 arg1 hESCs 465:469 hESCs 465:469 hESCs 465:469 Through a chemoproteomic approach, we developed a cell-surface proteome inventory containing 496 N-linked glycoproteins on human embryonic (hESCs) and induced PSCs (hiPSCs). 25068131 1 46 theme Detailed 122:129 arg1 knowledge 131:139 Detailed knowledge 122:139 Detailed knowledge of cell-surface proteins for isolating well-defined populations of human pluripotent stem cells (hPSCs) 122:243 Detailed knowledge of cell-surface proteins for isolating well-defined populations of human pluripotent stem cells (hPSCs) would significantly enhance their characterization and translational potential. 25068131 4 47 theme cell 812:815 arg1 isolation 817:825 cell isolation 812:825 cell isolation 812:825 The >30 positive and negative markers verified here by orthogonal approaches provide experimental justification for the rational selection of pluripotency and lineage markers, epitopes for cell isolation, and reagents for the characterization of putative hiPSC lines. 25068131 4 48 theme rational 743:750 arg1 selection 752:760 the rational selection 739:760 the rational selection of pluripotency and lineage markers, epitopes for cell isolation, and reagents for the characterization of putative hiPSC lines 739:888 The >30 positive and negative markers verified here by orthogonal approaches provide experimental justification for the rational selection of pluripotency and lineage markers, epitopes for cell isolation, and reagents for the characterization of putative hiPSC lines. 25068131 4 49 theme negative 644:651 arg1 markers 653:659 The >30 positive and negative markers 623:659 The >30 positive and negative markers verified here by orthogonal approaches 623:698 The >30 positive and negative markers verified here by orthogonal approaches provide experimental justification for the rational selection of pluripotency and lineage markers, epitopes for cell isolation, and reagents for the characterization of putative hiPSC lines. 25068131 5 50 theme chemoproteomic-defined 927:948 arg1 surfaceome 950:959 the chemoproteomic-defined surfaceome 923:959 the chemoproteomic-defined surfaceome 923:959 Comparative differences between the chemoproteomic-defined surfaceome and the transcriptome-predicted surfaceome directly led to the discovery that STF-31, a reported GLUT-1 inhibitor, is toxic to hPSCs and efficient for selective elimination of hPSCs from mixed cultures. 25068131 5 51 theme Comparative 891:901 arg1 differences 903:913 Comparative differences 891:913 Comparative differences between the chemoproteomic-defined surfaceome and the transcriptome-predicted surfaceome 891:1002 Comparative differences between the chemoproteomic-defined surfaceome and the transcriptome-predicted surfaceome directly led to the discovery that STF-31, a reported GLUT-1 inhibitor, is toxic to hPSCs and efficient for selective elimination of hPSCs from mixed cultures. 25068131 5 52 from cultures 1154:1161 arg1 elimination 1122:1132 selective elimination 1112:1132 selective elimination of hPSCs from mixed cultures 1112:1161 Comparative differences between the chemoproteomic-defined surfaceome and the transcriptome-predicted surfaceome directly led to the discovery that STF-31, a reported GLUT-1 inhibitor, is toxic to hPSCs and efficient for selective elimination of hPSCs from mixed cultures. 25068131 1 53 theme cell-surface 144:155 arg1 proteins 157:164 cell-surface proteins 144:164 cell-surface proteins 144:164 Detailed knowledge of cell-surface proteins for isolating well-defined populations of human pluripotent stem cells (hPSCs) would significantly enhance their characterization and translational potential. 25014350 0 0 theme respiratory 75:85 arg1 virus 96:100 porcine reproductive and respiratory syndrome virus 50:100 porcine reproductive and respiratory syndrome virus 50:100 Immune response to Fc tagged GP5 glycoproteins of porcine reproductive and respiratory syndrome virus. 25014350 2 1 theme epitope 472:478 arg1 presence 435:442 the presence 431:442 the presence of a non-neutralizing decoy epitope and shielding N-linked glycans close to its neutralizing epitope 431:543 Previous studies have demonstrated that the native GP5 glycoprotein is poorly immunogenic and not able to induce robust protective responses, probably due to the presence of a non-neutralizing decoy epitope and shielding N-linked glycans close to its neutralizing epitope. 25014350 4 2 theme native 1009:1014 arg1 GP5 1016:1018 the native GP5 1005:1018 the native GP5 present on the surface of purified PRRSV virons 1005:1066 Immunization studies showed that both GP5-Fc and GP5N-Fc elicited strong serum responses in the absence of adjuvant to the native GP5 present on the surface of purified PRRSV virons. 25014350 2 3 theme decoy 466:470 arg1 epitope 472:478 a non-neutralizing decoy epitope 447:478 a non-neutralizing decoy epitope 447:478 Previous studies have demonstrated that the native GP5 glycoprotein is poorly immunogenic and not able to induce robust protective responses, probably due to the presence of a non-neutralizing decoy epitope and shielding N-linked glycans close to its neutralizing epitope. 25014350 2 4 theme native 317:322 arg1 glycoprotein 328:339 the native GP5 glycoprotein 313:339 the native GP5 glycoprotein 313:339 Previous studies have demonstrated that the native GP5 glycoprotein is poorly immunogenic and not able to induce robust protective responses, probably due to the presence of a non-neutralizing decoy epitope and shielding N-linked glycans close to its neutralizing epitope. 25014350 2 4 theme native 317:322 arg1 immunogenic 351:361 immunogenic 351:361 immunogenic 351:361 Previous studies have demonstrated that the native GP5 glycoprotein is poorly immunogenic and not able to induce robust protective responses, probably due to the presence of a non-neutralizing decoy epitope and shielding N-linked glycans close to its neutralizing epitope. 25014350 1 5 gly glycoprotein 163:174 arg1 glycoprotein 214:225 the most abundant envelope glycoprotein 187:225 the most abundant envelope glycoprotein 187:225 Porcine reproductive and respiratory syndrome virus (PRRSV) glycoprotein 5 (GP5) is the most abundant envelope glycoprotein and a key target for neutralizing antibodies. 25014350 1 5 gly glycoprotein 163:174 arg1 glycoprotein 163:174 Porcine reproductive and respiratory syndrome virus (PRRSV) glycoprotein 5 103:176 Porcine reproductive and respiratory syndrome virus (PRRSV) glycoprotein 5 (GP5) 103:182 Porcine reproductive and respiratory syndrome virus (PRRSV) glycoprotein 5 (GP5) is the most abundant envelope glycoprotein and a key target for neutralizing antibodies. 25014350 1 5 gly glycoprotein 163:174 arg1 GP5 179:181 GP5 179:181 GP5 179:181 Porcine reproductive and respiratory syndrome virus (PRRSV) glycoprotein 5 (GP5) is the most abundant envelope glycoprotein and a key target for neutralizing antibodies. 25014350 5 6 theme specific 1227:1234 arg1 antibodies 1216:1225 antibodies 1216:1225 antibodies specific to PRRSV 1216:1243 Although GP5N-Fc failed in inducing significant titer of neutralizing antibodies in mice, GP5-Fc was shown as an effective inducer of neutralizing antibodies specific to PRRSV. 25014350 1 7 theme key 233:235 arg1 target 237:242 a key target 231:242 a key target for neutralizing antibodies 231:270 Porcine reproductive and respiratory syndrome virus (PRRSV) glycoprotein 5 (GP5) is the most abundant envelope glycoprotein and a key target for neutralizing antibodies. 25014350 0 8 theme virus 96:100 arg1 glycoproteins 33:45 GP5 glycoproteins 29:45 GP5 glycoproteins of porcine reproductive and respiratory syndrome virus 29:100 Immune response to Fc tagged GP5 glycoproteins of porcine reproductive and respiratory syndrome virus. 25014350 3 9 theme signal 656:661 arg1 peptide 663:669 its signal peptide 652:669 its signal peptide 652:669 In the present report, two Fc tagged GP5 proteins (GP5-Fc containing a truncated GP5 with the deletion of its signal peptide and transmembrane regions, and GP5N-Fc containing only the ectodomain of GP5) were designed based on the sequences of a highly pathogenic PRRSV strain and produced using a baculovirus/insect cell expression system. 25014350 4 10 theme serum 959:963 arg1 responses 965:973 strong serum responses 952:973 strong serum responses 952:973 Immunization studies showed that both GP5-Fc and GP5N-Fc elicited strong serum responses in the absence of adjuvant to the native GP5 present on the surface of purified PRRSV virons. 25014350 2 11 theme Previous 273:280 arg1 studies 282:288 Previous studies 273:288 Previous studies 273:288 Previous studies have demonstrated that the native GP5 glycoprotein is poorly immunogenic and not able to induce robust protective responses, probably due to the presence of a non-neutralizing decoy epitope and shielding N-linked glycans close to its neutralizing epitope. 25014350 4 12 theme present 1020:1026 arg1 GP5 1016:1018 the native GP5 1005:1018 the native GP5 present on the surface of purified PRRSV virons 1005:1066 Immunization studies showed that both GP5-Fc and GP5N-Fc elicited strong serum responses in the absence of adjuvant to the native GP5 present on the surface of purified PRRSV virons. 25014350 4 13 theme strong 952:957 arg1 responses 965:973 strong serum responses 952:973 strong serum responses 952:973 Immunization studies showed that both GP5-Fc and GP5N-Fc elicited strong serum responses in the absence of adjuvant to the native GP5 present on the surface of purified PRRSV virons. 25014350 0 14 theme syndrome 87:94 arg1 virus 96:100 porcine reproductive and respiratory syndrome virus 50:100 porcine reproductive and respiratory syndrome virus 50:100 Immune response to Fc tagged GP5 glycoproteins of porcine reproductive and respiratory syndrome virus. 25014350 5 15 theme neutralizing 1126:1137 arg1 antibodies 1139:1148 neutralizing antibodies 1126:1148 neutralizing antibodies 1126:1148 Although GP5N-Fc failed in inducing significant titer of neutralizing antibodies in mice, GP5-Fc was shown as an effective inducer of neutralizing antibodies specific to PRRSV. 25014350 3 16 theme expression 867:876 arg1 system 878:883 a baculovirus/insect cell expression system 841:883 a baculovirus/insect cell expression system 841:883 In the present report, two Fc tagged GP5 proteins (GP5-Fc containing a truncated GP5 with the deletion of its signal peptide and transmembrane regions, and GP5N-Fc containing only the ectodomain of GP5) were designed based on the sequences of a highly pathogenic PRRSV strain and produced using a baculovirus/insect cell expression system. 25014350 6 17 theme Fc 1306:1307 arg1 tag 1309:1311 Fc tag 1306:1311 Fc tag 1306:1311 Our results suggest that the modified GP5 glycoprotein with Fc tag has the potential to be a candidate for the future development of new generation vaccine against PRRSV infection. 25014350 2 18 theme glycans 503:509 arg1 presence 435:442 the presence 431:442 the presence of a non-neutralizing decoy epitope and shielding N-linked glycans close to its neutralizing epitope 431:543 Previous studies have demonstrated that the native GP5 glycoprotein is poorly immunogenic and not able to induce robust protective responses, probably due to the presence of a non-neutralizing decoy epitope and shielding N-linked glycans close to its neutralizing epitope. 25014350 6 19 contain has 1313:1315 arg1 glycoprotein 1288:1299 the modified GP5 glycoprotein 1271:1299 the modified GP5 glycoprotein with Fc tag 1271:1311 Our results suggest that the modified GP5 glycoprotein with Fc tag has the potential to be a candidate for the future development of new generation vaccine against PRRSV infection. 25014350 6 19 contain has 1313:1315 arg2 potential 1321:1329 the potential to be a candidate for the future development of new generation vaccine against PRRSV infection 1317:1424 the potential to be a candidate for the future development of new generation vaccine against PRRSV infection 1317:1424 Our results suggest that the modified GP5 glycoprotein with Fc tag has the potential to be a candidate for the future development of new generation vaccine against PRRSV infection. 25014350 1 20 gly glycoprotein 214:225 arg1 glycoprotein 214:225 the most abundant envelope glycoprotein 187:225 the most abundant envelope glycoprotein 187:225 Porcine reproductive and respiratory syndrome virus (PRRSV) glycoprotein 5 (GP5) is the most abundant envelope glycoprotein and a key target for neutralizing antibodies. 25014350 1 20 gly glycoprotein 214:225 arg1 glycoprotein 163:174 Porcine reproductive and respiratory syndrome virus (PRRSV) glycoprotein 5 103:176 Porcine reproductive and respiratory syndrome virus (PRRSV) glycoprotein 5 (GP5) 103:182 Porcine reproductive and respiratory syndrome virus (PRRSV) glycoprotein 5 (GP5) is the most abundant envelope glycoprotein and a key target for neutralizing antibodies. 25014350 2 21 theme N-linked 494:501 arg1 glycans 503:509 shielding N-linked glycans 484:509 shielding N-linked glycans 484:509 Previous studies have demonstrated that the native GP5 glycoprotein is poorly immunogenic and not able to induce robust protective responses, probably due to the presence of a non-neutralizing decoy epitope and shielding N-linked glycans close to its neutralizing epitope. 25014350 3 22 theme transmembrane 675:687 arg1 regions 689:695 transmembrane regions 675:695 transmembrane regions 675:695 In the present report, two Fc tagged GP5 proteins (GP5-Fc containing a truncated GP5 with the deletion of its signal peptide and transmembrane regions, and GP5N-Fc containing only the ectodomain of GP5) were designed based on the sequences of a highly pathogenic PRRSV strain and produced using a baculovirus/insect cell expression system. 25014350 2 23 theme non-neutralizing 449:464 arg1 epitope 472:478 a non-neutralizing decoy epitope 447:478 a non-neutralizing decoy epitope 447:478 Previous studies have demonstrated that the native GP5 glycoprotein is poorly immunogenic and not able to induce robust protective responses, probably due to the presence of a non-neutralizing decoy epitope and shielding N-linked glycans close to its neutralizing epitope. 25014350 5 24 theme effective 1182:1190 arg1 GP5-Fc 1159:1164 GP5-Fc 1159:1164 GP5-Fc 1159:1164 Although GP5N-Fc failed in inducing significant titer of neutralizing antibodies in mice, GP5-Fc was shown as an effective inducer of neutralizing antibodies specific to PRRSV. 25014350 5 24 theme effective 1182:1190 arg1 inducer 1192:1198 an effective inducer 1179:1198 an effective inducer of neutralizing antibodies specific to PRRSV 1179:1243 Although GP5N-Fc failed in inducing significant titer of neutralizing antibodies in mice, GP5-Fc was shown as an effective inducer of neutralizing antibodies specific to PRRSV. 25014350 3 25 theme baculovirus/insect 843:860 arg1 system 878:883 a baculovirus/insect cell expression system 841:883 a baculovirus/insect cell expression system 841:883 In the present report, two Fc tagged GP5 proteins (GP5-Fc containing a truncated GP5 with the deletion of its signal peptide and transmembrane regions, and GP5N-Fc containing only the ectodomain of GP5) were designed based on the sequences of a highly pathogenic PRRSV strain and produced using a baculovirus/insect cell expression system. 25014350 4 26 theme adjuvant 993:1000 arg1 absence 982:988 the absence 978:988 the absence of adjuvant to the native GP5 present on the surface of purified PRRSV virons 978:1066 Immunization studies showed that both GP5-Fc and GP5N-Fc elicited strong serum responses in the absence of adjuvant to the native GP5 present on the surface of purified PRRSV virons. 25014350 3 27 theme regions 689:695 arg1 deletion 640:647 the deletion 636:647 the deletion of its signal peptide and transmembrane regions 636:695 In the present report, two Fc tagged GP5 proteins (GP5-Fc containing a truncated GP5 with the deletion of its signal peptide and transmembrane regions, and GP5N-Fc containing only the ectodomain of GP5) were designed based on the sequences of a highly pathogenic PRRSV strain and produced using a baculovirus/insect cell expression system. 25014350 4 28 attach present 1020:1026 arg1 surface 1035:1041 the surface 1031:1041 the surface of purified PRRSV virons 1031:1066 Immunization studies showed that both GP5-Fc and GP5N-Fc elicited strong serum responses in the absence of adjuvant to the native GP5 present on the surface of purified PRRSV virons. 25014350 4 28 attach present 1020:1026 arg2 GP5 1016:1018 the native GP5 1005:1018 the native GP5 present on the surface of purified PRRSV virons 1005:1066 Immunization studies showed that both GP5-Fc and GP5N-Fc elicited strong serum responses in the absence of adjuvant to the native GP5 present on the surface of purified PRRSV virons. 25014350 2 29 theme shielding 484:492 arg1 glycans 503:509 shielding N-linked glycans 484:509 shielding N-linked glycans 484:509 Previous studies have demonstrated that the native GP5 glycoprotein is poorly immunogenic and not able to induce robust protective responses, probably due to the presence of a non-neutralizing decoy epitope and shielding N-linked glycans close to its neutralizing epitope. 25014350 3 30 contain containing 710:719 arg1 proteins 587:594 two Fc tagged GP5 proteins 569:594 two Fc tagged GP5 proteins (GP5-Fc containing a truncated GP5 with the deletion of its signal peptide and transmembrane regions, and GP5N-Fc containing only the ectodomain of GP5) 569:747 In the present report, two Fc tagged GP5 proteins (GP5-Fc containing a truncated GP5 with the deletion of its signal peptide and transmembrane regions, and GP5N-Fc containing only the ectodomain of GP5) were designed based on the sequences of a highly pathogenic PRRSV strain and produced using a baculovirus/insect cell expression system. 25014350 3 30 contain containing 710:719 arg1 GP5N-Fc 702:708 GP5N-Fc 702:708 GP5N-Fc containing only the ectodomain of GP5 702:746 In the present report, two Fc tagged GP5 proteins (GP5-Fc containing a truncated GP5 with the deletion of its signal peptide and transmembrane regions, and GP5N-Fc containing only the ectodomain of GP5) were designed based on the sequences of a highly pathogenic PRRSV strain and produced using a baculovirus/insect cell expression system. 25014350 3 30 contain containing 710:719 arg2 GP5 744:746 GP5 744:746 GP5 744:746 In the present report, two Fc tagged GP5 proteins (GP5-Fc containing a truncated GP5 with the deletion of its signal peptide and transmembrane regions, and GP5N-Fc containing only the ectodomain of GP5) were designed based on the sequences of a highly pathogenic PRRSV strain and produced using a baculovirus/insect cell expression system. 25014350 3 30 contain containing 710:719 arg2 ectodomain 730:739 only the ectodomain 721:739 only the ectodomain of GP5 721:746 In the present report, two Fc tagged GP5 proteins (GP5-Fc containing a truncated GP5 with the deletion of its signal peptide and transmembrane regions, and GP5N-Fc containing only the ectodomain of GP5) were designed based on the sequences of a highly pathogenic PRRSV strain and produced using a baculovirus/insect cell expression system. 25014350 3 31 theme cell 862:865 arg1 system 878:883 a baculovirus/insect cell expression system 841:883 a baculovirus/insect cell expression system 841:883 In the present report, two Fc tagged GP5 proteins (GP5-Fc containing a truncated GP5 with the deletion of its signal peptide and transmembrane regions, and GP5N-Fc containing only the ectodomain of GP5) were designed based on the sequences of a highly pathogenic PRRSV strain and produced using a baculovirus/insect cell expression system. 25014350 0 32 theme Immune 0:5 arg1 response 7:14 Immune response 0:14 Immune response to Fc 0:20 Immune response to Fc tagged GP5 glycoproteins of porcine reproductive and respiratory syndrome virus. 25014350 1 33 theme neutralizing 248:259 arg1 antibodies 261:270 neutralizing antibodies 248:270 neutralizing antibodies 248:270 Porcine reproductive and respiratory syndrome virus (PRRSV) glycoprotein 5 (GP5) is the most abundant envelope glycoprotein and a key target for neutralizing antibodies. 25014350 6 34 theme PRRSV 1410:1414 arg1 infection 1416:1424 PRRSV infection 1410:1424 PRRSV infection 1410:1424 Our results suggest that the modified GP5 glycoprotein with Fc tag has the potential to be a candidate for the future development of new generation vaccine against PRRSV infection. 25014350 4 35 theme virons 1061:1066 arg1 surface 1035:1041 the surface 1031:1041 the surface of purified PRRSV virons 1031:1066 Immunization studies showed that both GP5-Fc and GP5N-Fc elicited strong serum responses in the absence of adjuvant to the native GP5 present on the surface of purified PRRSV virons. 25014350 6 36 theme new 1379:1381 arg1 vaccine 1394:1400 new generation vaccine 1379:1400 new generation vaccine against PRRSV infection 1379:1424 Our results suggest that the modified GP5 glycoprotein with Fc tag has the potential to be a candidate for the future development of new generation vaccine against PRRSV infection. 25014350 3 37 theme GP5 583:585 arg1 proteins 587:594 two Fc tagged GP5 proteins 569:594 two Fc tagged GP5 proteins (GP5-Fc containing a truncated GP5 with the deletion of its signal peptide and transmembrane regions, and GP5N-Fc containing only the ectodomain of GP5) 569:747 In the present report, two Fc tagged GP5 proteins (GP5-Fc containing a truncated GP5 with the deletion of its signal peptide and transmembrane regions, and GP5N-Fc containing only the ectodomain of GP5) were designed based on the sequences of a highly pathogenic PRRSV strain and produced using a baculovirus/insect cell expression system. 25014350 3 37 theme GP5 583:585 arg1 GP5N-Fc 702:708 GP5N-Fc 702:708 GP5N-Fc containing only the ectodomain of GP5 702:746 In the present report, two Fc tagged GP5 proteins (GP5-Fc containing a truncated GP5 with the deletion of its signal peptide and transmembrane regions, and GP5N-Fc containing only the ectodomain of GP5) were designed based on the sequences of a highly pathogenic PRRSV strain and produced using a baculovirus/insect cell expression system. 25014350 3 37 theme GP5 583:585 arg1 GP5-Fc 597:602 GP5-Fc 597:602 GP5-Fc containing a truncated GP5 with the deletion of its signal peptide and transmembrane regions 597:695 In the present report, two Fc tagged GP5 proteins (GP5-Fc containing a truncated GP5 with the deletion of its signal peptide and transmembrane regions, and GP5N-Fc containing only the ectodomain of GP5) were designed based on the sequences of a highly pathogenic PRRSV strain and produced using a baculovirus/insect cell expression system. 25014350 4 38 theme Immunization 886:897 arg1 studies 899:905 Immunization studies 886:905 Immunization studies 886:905 Immunization studies showed that both GP5-Fc and GP5N-Fc elicited strong serum responses in the absence of adjuvant to the native GP5 present on the surface of purified PRRSV virons. 25014350 4 39 theme PRRSV 1055:1059 arg1 virons 1061:1066 purified PRRSV virons 1046:1066 purified PRRSV virons 1046:1066 Immunization studies showed that both GP5-Fc and GP5N-Fc elicited strong serum responses in the absence of adjuvant to the native GP5 present on the surface of purified PRRSV virons. 25014350 3 40 dep proteins 587:594 arg1 proteins 587:594 two Fc tagged GP5 proteins 569:594 two Fc tagged GP5 proteins (GP5-Fc containing a truncated GP5 with the deletion of its signal peptide and transmembrane regions, and GP5N-Fc containing only the ectodomain of GP5) 569:747 In the present report, two Fc tagged GP5 proteins (GP5-Fc containing a truncated GP5 with the deletion of its signal peptide and transmembrane regions, and GP5N-Fc containing only the ectodomain of GP5) were designed based on the sequences of a highly pathogenic PRRSV strain and produced using a baculovirus/insect cell expression system. 25014350 3 40 dep proteins 587:594 arg1 GP5N-Fc 702:708 GP5N-Fc 702:708 GP5N-Fc containing only the ectodomain of GP5 702:746 In the present report, two Fc tagged GP5 proteins (GP5-Fc containing a truncated GP5 with the deletion of its signal peptide and transmembrane regions, and GP5N-Fc containing only the ectodomain of GP5) were designed based on the sequences of a highly pathogenic PRRSV strain and produced using a baculovirus/insect cell expression system. 25014350 3 40 dep proteins 587:594 arg1 GP5-Fc 597:602 GP5-Fc 597:602 GP5-Fc containing a truncated GP5 with the deletion of its signal peptide and transmembrane regions 597:695 In the present report, two Fc tagged GP5 proteins (GP5-Fc containing a truncated GP5 with the deletion of its signal peptide and transmembrane regions, and GP5N-Fc containing only the ectodomain of GP5) were designed based on the sequences of a highly pathogenic PRRSV strain and produced using a baculovirus/insect cell expression system. 25014350 3 41 theme truncated 617:625 arg1 GP5 627:629 a truncated GP5 615:629 a truncated GP5 with the deletion of its signal peptide and transmembrane regions 615:695 In the present report, two Fc tagged GP5 proteins (GP5-Fc containing a truncated GP5 with the deletion of its signal peptide and transmembrane regions, and GP5N-Fc containing only the ectodomain of GP5) were designed based on the sequences of a highly pathogenic PRRSV strain and produced using a baculovirus/insect cell expression system. 25014350 3 42 contain containing 604:613 arg1 proteins 587:594 two Fc tagged GP5 proteins 569:594 two Fc tagged GP5 proteins (GP5-Fc containing a truncated GP5 with the deletion of its signal peptide and transmembrane regions, and GP5N-Fc containing only the ectodomain of GP5) 569:747 In the present report, two Fc tagged GP5 proteins (GP5-Fc containing a truncated GP5 with the deletion of its signal peptide and transmembrane regions, and GP5N-Fc containing only the ectodomain of GP5) were designed based on the sequences of a highly pathogenic PRRSV strain and produced using a baculovirus/insect cell expression system. 25014350 3 42 contain containing 604:613 arg2 GP5 627:629 a truncated GP5 615:629 a truncated GP5 with the deletion of its signal peptide and transmembrane regions 615:695 In the present report, two Fc tagged GP5 proteins (GP5-Fc containing a truncated GP5 with the deletion of its signal peptide and transmembrane regions, and GP5N-Fc containing only the ectodomain of GP5) were designed based on the sequences of a highly pathogenic PRRSV strain and produced using a baculovirus/insect cell expression system. 25014350 3 42 contain containing 604:613 arg1 GP5-Fc 597:602 GP5-Fc 597:602 GP5-Fc containing a truncated GP5 with the deletion of its signal peptide and transmembrane regions 597:695 In the present report, two Fc tagged GP5 proteins (GP5-Fc containing a truncated GP5 with the deletion of its signal peptide and transmembrane regions, and GP5N-Fc containing only the ectodomain of GP5) were designed based on the sequences of a highly pathogenic PRRSV strain and produced using a baculovirus/insect cell expression system. 25014350 0 43 theme GP5 29:31 arg1 glycoproteins 33:45 GP5 glycoproteins 29:45 GP5 glycoproteins of porcine reproductive and respiratory syndrome virus 29:100 Immune response to Fc tagged GP5 glycoproteins of porcine reproductive and respiratory syndrome virus. 25014350 2 44 theme neutralizing 524:535 arg1 epitope 537:543 its neutralizing epitope 520:543 its neutralizing epitope 520:543 Previous studies have demonstrated that the native GP5 glycoprotein is poorly immunogenic and not able to induce robust protective responses, probably due to the presence of a non-neutralizing decoy epitope and shielding N-linked glycans close to its neutralizing epitope. 25014350 3 45 dep designed 754:761 arg1 based 763:767 based 763:767 based 763:767 In the present report, two Fc tagged GP5 proteins (GP5-Fc containing a truncated GP5 with the deletion of its signal peptide and transmembrane regions, and GP5N-Fc containing only the ectodomain of GP5) were designed based on the sequences of a highly pathogenic PRRSV strain and produced using a baculovirus/insect cell expression system. 25014350 3 45 dep designed 754:761 arg1 produced 826:833 produced 826:833 produced using a baculovirus/insect cell expression system 826:883 In the present report, two Fc tagged GP5 proteins (GP5-Fc containing a truncated GP5 with the deletion of its signal peptide and transmembrane regions, and GP5N-Fc containing only the ectodomain of GP5) were designed based on the sequences of a highly pathogenic PRRSV strain and produced using a baculovirus/insect cell expression system. 25014350 3 46 theme Fc 573:574 arg1 proteins 587:594 two Fc tagged GP5 proteins 569:594 two Fc tagged GP5 proteins (GP5-Fc containing a truncated GP5 with the deletion of its signal peptide and transmembrane regions, and GP5N-Fc containing only the ectodomain of GP5) 569:747 In the present report, two Fc tagged GP5 proteins (GP5-Fc containing a truncated GP5 with the deletion of its signal peptide and transmembrane regions, and GP5N-Fc containing only the ectodomain of GP5) were designed based on the sequences of a highly pathogenic PRRSV strain and produced using a baculovirus/insect cell expression system. 25014350 3 46 theme Fc 573:574 arg1 GP5N-Fc 702:708 GP5N-Fc 702:708 GP5N-Fc containing only the ectodomain of GP5 702:746 In the present report, two Fc tagged GP5 proteins (GP5-Fc containing a truncated GP5 with the deletion of its signal peptide and transmembrane regions, and GP5N-Fc containing only the ectodomain of GP5) were designed based on the sequences of a highly pathogenic PRRSV strain and produced using a baculovirus/insect cell expression system. 25014350 3 46 theme Fc 573:574 arg1 GP5-Fc 597:602 GP5-Fc 597:602 GP5-Fc containing a truncated GP5 with the deletion of its signal peptide and transmembrane regions 597:695 In the present report, two Fc tagged GP5 proteins (GP5-Fc containing a truncated GP5 with the deletion of its signal peptide and transmembrane regions, and GP5N-Fc containing only the ectodomain of GP5) were designed based on the sequences of a highly pathogenic PRRSV strain and produced using a baculovirus/insect cell expression system. 25014350 3 47 with GP5 627:629 arg1 deletion 640:647 the deletion 636:647 the deletion of its signal peptide and transmembrane regions 636:695 In the present report, two Fc tagged GP5 proteins (GP5-Fc containing a truncated GP5 with the deletion of its signal peptide and transmembrane regions, and GP5N-Fc containing only the ectodomain of GP5) were designed based on the sequences of a highly pathogenic PRRSV strain and produced using a baculovirus/insect cell expression system. 25014350 2 48 theme protective 393:402 arg1 responses 404:412 robust protective responses 386:412 robust protective responses 386:412 Previous studies have demonstrated that the native GP5 glycoprotein is poorly immunogenic and not able to induce robust protective responses, probably due to the presence of a non-neutralizing decoy epitope and shielding N-linked glycans close to its neutralizing epitope. 25014350 6 49 theme future 1357:1362 arg1 development 1364:1374 the future development 1353:1374 the future development of new generation vaccine against PRRSV infection 1353:1424 Our results suggest that the modified GP5 glycoprotein with Fc tag has the potential to be a candidate for the future development of new generation vaccine against PRRSV infection. 25014350 3 50 theme GP5 744:746 arg1 GP5 744:746 GP5 744:746 GP5 744:746 In the present report, two Fc tagged GP5 proteins (GP5-Fc containing a truncated GP5 with the deletion of its signal peptide and transmembrane regions, and GP5N-Fc containing only the ectodomain of GP5) were designed based on the sequences of a highly pathogenic PRRSV strain and produced using a baculovirus/insect cell expression system. 25014350 3 50 theme GP5 744:746 arg1 ectodomain 730:739 only the ectodomain 721:739 only the ectodomain of GP5 721:746 In the present report, two Fc tagged GP5 proteins (GP5-Fc containing a truncated GP5 with the deletion of its signal peptide and transmembrane regions, and GP5N-Fc containing only the ectodomain of GP5) were designed based on the sequences of a highly pathogenic PRRSV strain and produced using a baculovirus/insect cell expression system. 25014350 6 51 theme GP5 1284:1286 arg1 glycoprotein 1288:1299 the modified GP5 glycoprotein 1271:1299 the modified GP5 glycoprotein with Fc tag 1271:1311 Our results suggest that the modified GP5 glycoprotein with Fc tag has the potential to be a candidate for the future development of new generation vaccine against PRRSV infection. 25014350 3 52 theme tagged 576:581 arg1 proteins 587:594 two Fc tagged GP5 proteins 569:594 two Fc tagged GP5 proteins (GP5-Fc containing a truncated GP5 with the deletion of its signal peptide and transmembrane regions, and GP5N-Fc containing only the ectodomain of GP5) 569:747 In the present report, two Fc tagged GP5 proteins (GP5-Fc containing a truncated GP5 with the deletion of its signal peptide and transmembrane regions, and GP5N-Fc containing only the ectodomain of GP5) were designed based on the sequences of a highly pathogenic PRRSV strain and produced using a baculovirus/insect cell expression system. 25014350 3 52 theme tagged 576:581 arg1 GP5N-Fc 702:708 GP5N-Fc 702:708 GP5N-Fc containing only the ectodomain of GP5 702:746 In the present report, two Fc tagged GP5 proteins (GP5-Fc containing a truncated GP5 with the deletion of its signal peptide and transmembrane regions, and GP5N-Fc containing only the ectodomain of GP5) were designed based on the sequences of a highly pathogenic PRRSV strain and produced using a baculovirus/insect cell expression system. 25014350 3 52 theme tagged 576:581 arg1 GP5-Fc 597:602 GP5-Fc 597:602 GP5-Fc containing a truncated GP5 with the deletion of its signal peptide and transmembrane regions 597:695 In the present report, two Fc tagged GP5 proteins (GP5-Fc containing a truncated GP5 with the deletion of its signal peptide and transmembrane regions, and GP5N-Fc containing only the ectodomain of GP5) were designed based on the sequences of a highly pathogenic PRRSV strain and produced using a baculovirus/insect cell expression system. 25014350 2 53 theme robust 386:391 arg1 responses 404:412 robust protective responses 386:412 robust protective responses 386:412 Previous studies have demonstrated that the native GP5 glycoprotein is poorly immunogenic and not able to induce robust protective responses, probably due to the presence of a non-neutralizing decoy epitope and shielding N-linked glycans close to its neutralizing epitope. 25014350 5 54 theme significant 1105:1115 arg1 titer 1117:1121 significant titer 1105:1121 significant titer of neutralizing antibodies 1105:1148 Although GP5N-Fc failed in inducing significant titer of neutralizing antibodies in mice, GP5-Fc was shown as an effective inducer of neutralizing antibodies specific to PRRSV. 25014350 6 55 theme modified 1275:1282 arg1 glycoprotein 1288:1299 the modified GP5 glycoprotein 1271:1299 the modified GP5 glycoprotein with Fc tag 1271:1311 Our results suggest that the modified GP5 glycoprotein with Fc tag has the potential to be a candidate for the future development of new generation vaccine against PRRSV infection. 25014350 6 56 theme generation 1383:1392 arg1 vaccine 1394:1400 new generation vaccine 1379:1400 new generation vaccine against PRRSV infection 1379:1424 Our results suggest that the modified GP5 glycoprotein with Fc tag has the potential to be a candidate for the future development of new generation vaccine against PRRSV infection. 25014350 1 57 theme reproductive 111:122 arg1 glycoprotein 214:225 the most abundant envelope glycoprotein 187:225 the most abundant envelope glycoprotein 187:225 Porcine reproductive and respiratory syndrome virus (PRRSV) glycoprotein 5 (GP5) is the most abundant envelope glycoprotein and a key target for neutralizing antibodies. 25014350 1 57 theme reproductive 111:122 arg1 glycoprotein 163:174 Porcine reproductive and respiratory syndrome virus (PRRSV) glycoprotein 5 103:176 Porcine reproductive and respiratory syndrome virus (PRRSV) glycoprotein 5 (GP5) 103:182 Porcine reproductive and respiratory syndrome virus (PRRSV) glycoprotein 5 (GP5) is the most abundant envelope glycoprotein and a key target for neutralizing antibodies. 25014350 1 57 theme reproductive 111:122 arg1 GP5 179:181 GP5 179:181 GP5 179:181 Porcine reproductive and respiratory syndrome virus (PRRSV) glycoprotein 5 (GP5) is the most abundant envelope glycoprotein and a key target for neutralizing antibodies. 25014350 2 58 gly glycoprotein 328:339 arg1 glycoprotein 328:339 the native GP5 glycoprotein 313:339 the native GP5 glycoprotein 313:339 Previous studies have demonstrated that the native GP5 glycoprotein is poorly immunogenic and not able to induce robust protective responses, probably due to the presence of a non-neutralizing decoy epitope and shielding N-linked glycans close to its neutralizing epitope. 25014350 2 58 gly glycoprotein 328:339 arg1 immunogenic 351:361 immunogenic 351:361 immunogenic 351:361 Previous studies have demonstrated that the native GP5 glycoprotein is poorly immunogenic and not able to induce robust protective responses, probably due to the presence of a non-neutralizing decoy epitope and shielding N-linked glycans close to its neutralizing epitope. 25014350 2 59 theme GP5 324:326 arg1 glycoprotein 328:339 the native GP5 glycoprotein 313:339 the native GP5 glycoprotein 313:339 Previous studies have demonstrated that the native GP5 glycoprotein is poorly immunogenic and not able to induce robust protective responses, probably due to the presence of a non-neutralizing decoy epitope and shielding N-linked glycans close to its neutralizing epitope. 25014350 2 59 theme GP5 324:326 arg1 immunogenic 351:361 immunogenic 351:361 immunogenic 351:361 Previous studies have demonstrated that the native GP5 glycoprotein is poorly immunogenic and not able to induce robust protective responses, probably due to the presence of a non-neutralizing decoy epitope and shielding N-linked glycans close to its neutralizing epitope. 25014350 3 60 theme PRRSV 809:813 arg1 strain 815:820 a highly pathogenic PRRSV strain 789:820 a highly pathogenic PRRSV strain 789:820 In the present report, two Fc tagged GP5 proteins (GP5-Fc containing a truncated GP5 with the deletion of its signal peptide and transmembrane regions, and GP5N-Fc containing only the ectodomain of GP5) were designed based on the sequences of a highly pathogenic PRRSV strain and produced using a baculovirus/insect cell expression system. 25014350 3 61 theme present 553:559 arg1 report 561:566 the present report 549:566 the present report 549:566 In the present report, two Fc tagged GP5 proteins (GP5-Fc containing a truncated GP5 with the deletion of its signal peptide and transmembrane regions, and GP5N-Fc containing only the ectodomain of GP5) were designed based on the sequences of a highly pathogenic PRRSV strain and produced using a baculovirus/insect cell expression system. 25014350 1 62 theme respiratory 128:138 arg1 PRRSV 156:160 PRRSV 156:160 PRRSV 156:160 Porcine reproductive and respiratory syndrome virus (PRRSV) glycoprotein 5 (GP5) is the most abundant envelope glycoprotein and a key target for neutralizing antibodies. 25014350 1 62 theme respiratory 128:138 arg1 virus 149:153 respiratory syndrome virus 128:153 respiratory syndrome virus (PRRSV) 128:161 Porcine reproductive and respiratory syndrome virus (PRRSV) glycoprotein 5 (GP5) is the most abundant envelope glycoprotein and a key target for neutralizing antibodies. 25014350 3 63 theme strain 815:820 arg1 sequences 776:784 the sequences 772:784 the sequences of a highly pathogenic PRRSV strain 772:820 In the present report, two Fc tagged GP5 proteins (GP5-Fc containing a truncated GP5 with the deletion of its signal peptide and transmembrane regions, and GP5N-Fc containing only the ectodomain of GP5) were designed based on the sequences of a highly pathogenic PRRSV strain and produced using a baculovirus/insect cell expression system. 25014350 1 64 theme abundant 196:203 arg1 glycoprotein 214:225 the most abundant envelope glycoprotein 187:225 the most abundant envelope glycoprotein 187:225 Porcine reproductive and respiratory syndrome virus (PRRSV) glycoprotein 5 (GP5) is the most abundant envelope glycoprotein and a key target for neutralizing antibodies. 25014350 1 64 theme abundant 196:203 arg1 glycoprotein 163:174 Porcine reproductive and respiratory syndrome virus (PRRSV) glycoprotein 5 103:176 Porcine reproductive and respiratory syndrome virus (PRRSV) glycoprotein 5 (GP5) 103:182 Porcine reproductive and respiratory syndrome virus (PRRSV) glycoprotein 5 (GP5) is the most abundant envelope glycoprotein and a key target for neutralizing antibodies. 25014350 5 65 theme antibodies 1139:1148 arg1 titer 1117:1121 significant titer 1105:1121 significant titer of neutralizing antibodies 1105:1148 Although GP5N-Fc failed in inducing significant titer of neutralizing antibodies in mice, GP5-Fc was shown as an effective inducer of neutralizing antibodies specific to PRRSV. 25014350 1 66 theme syndrome 140:147 arg1 PRRSV 156:160 PRRSV 156:160 PRRSV 156:160 Porcine reproductive and respiratory syndrome virus (PRRSV) glycoprotein 5 (GP5) is the most abundant envelope glycoprotein and a key target for neutralizing antibodies. 25014350 1 66 theme syndrome 140:147 arg1 virus 149:153 respiratory syndrome virus 128:153 respiratory syndrome virus (PRRSV) 128:161 Porcine reproductive and respiratory syndrome virus (PRRSV) glycoprotein 5 (GP5) is the most abundant envelope glycoprotein and a key target for neutralizing antibodies. 25014350 4 67 theme purified 1046:1053 arg1 virons 1061:1066 purified PRRSV virons 1046:1066 purified PRRSV virons 1046:1066 Immunization studies showed that both GP5-Fc and GP5N-Fc elicited strong serum responses in the absence of adjuvant to the native GP5 present on the surface of purified PRRSV virons. 25014350 1 68 theme envelope 205:212 arg1 glycoprotein 214:225 the most abundant envelope glycoprotein 187:225 the most abundant envelope glycoprotein 187:225 Porcine reproductive and respiratory syndrome virus (PRRSV) glycoprotein 5 (GP5) is the most abundant envelope glycoprotein and a key target for neutralizing antibodies. 25014350 1 68 theme envelope 205:212 arg1 glycoprotein 163:174 Porcine reproductive and respiratory syndrome virus (PRRSV) glycoprotein 5 103:176 Porcine reproductive and respiratory syndrome virus (PRRSV) glycoprotein 5 (GP5) 103:182 Porcine reproductive and respiratory syndrome virus (PRRSV) glycoprotein 5 (GP5) is the most abundant envelope glycoprotein and a key target for neutralizing antibodies. 25014350 0 69 theme reproductive 58:69 arg1 virus 96:100 porcine reproductive and respiratory syndrome virus 50:100 porcine reproductive and respiratory syndrome virus 50:100 Immune response to Fc tagged GP5 glycoproteins of porcine reproductive and respiratory syndrome virus. 25014350 6 70 gly glycoprotein 1288:1299 arg1 glycoprotein 1288:1299 the modified GP5 glycoprotein 1271:1299 the modified GP5 glycoprotein with Fc tag 1271:1311 Our results suggest that the modified GP5 glycoprotein with Fc tag has the potential to be a candidate for the future development of new generation vaccine against PRRSV infection. 25014350 0 71 gly glycoproteins 33:45 arg1 glycoproteins 33:45 GP5 glycoproteins 29:45 GP5 glycoproteins of porcine reproductive and respiratory syndrome virus 29:100 Immune response to Fc tagged GP5 glycoproteins of porcine reproductive and respiratory syndrome virus. 25014350 2 72 link N-linked 494:501 arg1 glycans 503:509 shielding N-linked glycans 484:509 shielding N-linked glycans 484:509 Previous studies have demonstrated that the native GP5 glycoprotein is poorly immunogenic and not able to induce robust protective responses, probably due to the presence of a non-neutralizing decoy epitope and shielding N-linked glycans close to its neutralizing epitope. 25014350 1 73 theme virus 149:153 arg1 glycoprotein 214:225 the most abundant envelope glycoprotein 187:225 the most abundant envelope glycoprotein 187:225 Porcine reproductive and respiratory syndrome virus (PRRSV) glycoprotein 5 (GP5) is the most abundant envelope glycoprotein and a key target for neutralizing antibodies. 25014350 1 73 theme virus 149:153 arg1 glycoprotein 163:174 Porcine reproductive and respiratory syndrome virus (PRRSV) glycoprotein 5 103:176 Porcine reproductive and respiratory syndrome virus (PRRSV) glycoprotein 5 (GP5) 103:182 Porcine reproductive and respiratory syndrome virus (PRRSV) glycoprotein 5 (GP5) is the most abundant envelope glycoprotein and a key target for neutralizing antibodies. 25014350 1 73 theme virus 149:153 arg1 GP5 179:181 GP5 179:181 GP5 179:181 Porcine reproductive and respiratory syndrome virus (PRRSV) glycoprotein 5 (GP5) is the most abundant envelope glycoprotein and a key target for neutralizing antibodies. 25014350 3 74 theme pathogenic 798:807 arg1 strain 815:820 a highly pathogenic PRRSV strain 789:820 a highly pathogenic PRRSV strain 789:820 In the present report, two Fc tagged GP5 proteins (GP5-Fc containing a truncated GP5 with the deletion of its signal peptide and transmembrane regions, and GP5N-Fc containing only the ectodomain of GP5) were designed based on the sequences of a highly pathogenic PRRSV strain and produced using a baculovirus/insect cell expression system. 25014350 6 75 with glycoprotein 1288:1299 arg1 tag 1309:1311 Fc tag 1306:1311 Fc tag 1306:1311 Our results suggest that the modified GP5 glycoprotein with Fc tag has the potential to be a candidate for the future development of new generation vaccine against PRRSV infection. 25014350 3 76 theme peptide 663:669 arg1 deletion 640:647 the deletion 636:647 the deletion of its signal peptide and transmembrane regions 636:695 In the present report, two Fc tagged GP5 proteins (GP5-Fc containing a truncated GP5 with the deletion of its signal peptide and transmembrane regions, and GP5N-Fc containing only the ectodomain of GP5) were designed based on the sequences of a highly pathogenic PRRSV strain and produced using a baculovirus/insect cell expression system. 25014350 6 77 theme vaccine 1394:1400 arg1 development 1364:1374 the future development 1353:1374 the future development of new generation vaccine against PRRSV infection 1353:1424 Our results suggest that the modified GP5 glycoprotein with Fc tag has the potential to be a candidate for the future development of new generation vaccine against PRRSV infection. 24960276 7 0 theme unequal 2138:2144 arg1 efficiencies 2146:2157 unequal efficiencies 2138:2157 unequal efficiencies 2138:2157 Isotope labeling at the protein level can minimize potential uncertainty originating from unequal efficiencies in protein digestion in separate vials and retrieval of each labeled peptide when labeling takes place at the peptide level. 24960276 8 1 theme protein 2397:2403 arg1 quantification 2405:2418 protein quantification 2397:2418 protein quantification easily accessible 2397:2436 In addition, the labeling reagents for the iCCM method are readily obtained at a reasonable cost, which can make protein quantification easily accessible. 24960276 3 2 theme proteome 733:740 arg1 samples 742:748 CM-/iCCM-labeled proteome samples 716:748 CM-/iCCM-labeled proteome samples 716:748 CM-/iCCM-labeled proteome samples are mixed for proteolysis; then, online enrichment of N-glycopeptides using lectin affinity is carried out in an mHFER before nLC-MS/MS for quantification using multiple reaction monitoring (MRM). 24960276 1 3 theme isotope-coded 314:326 arg1 iCCM 350:353 iCCM 350:353 iCCM 350:353 This paper introduces a simple, inexpensive, and robust quantitative proteomic method for quantifying N-linked glycoproteins based on isotope-coded carbamidomethylation (iCCM) incorporated into an online microbore hollow fiber enzyme reactor and nanoflow liquid chromatography-tandem mass spectrometry (mHFER-nLC-MS/MS). 24960276 1 3 theme isotope-coded 314:326 arg1 carbamidomethylation 328:347 isotope-coded carbamidomethylation 314:347 isotope-coded carbamidomethylation (iCCM) incorporated into an online microbore hollow fiber enzyme reactor and nanoflow liquid chromatography-tandem mass spectrometry (mHFER-nLC-MS/MS) 314:498 This paper introduces a simple, inexpensive, and robust quantitative proteomic method for quantifying N-linked glycoproteins based on isotope-coded carbamidomethylation (iCCM) incorporated into an online microbore hollow fiber enzyme reactor and nanoflow liquid chromatography-tandem mass spectrometry (mHFER-nLC-MS/MS). 24960276 6 4 theme iCCM 1882:1885 arg1 method 1887:1892 The iCCM method 1878:1892 The iCCM method 1878:1892 Although iCCM quantitation with mHFER-nLC-MS/MS applies only to glycopeptides with Cys residue, the method can offer several advantages over other labeling methods when applied to targeted glycoproteins: The iCCM method does not require an additional labeling reaction under special conditions nor complicated procedures to purify labeled products using additional columns. 24960276 5 5 theme cancer 1618:1623 arg1 sera 1635:1638 liver cancer patients' sera 1612:1638 liver cancer patients' sera 1612:1638 The iCCM quantitation with mHFER-nLC-MS/MS was evaluated with three standard glycoproteins (α-1-acid glycoproteins, fetuin and transferrin) and then applied to serum glycoproteins from liver cancer patients and controls, resulting in successful quantification of 73 N-glycopeptides (from 49 N-glycoproteins), among which 19 N-glycopeptides from 14 N-glycoproteins showed more than a 2.5-fold aberrant change in liver cancer patients' sera compared with the pooled control. 24960276 7 6 theme potential 2099:2107 arg1 uncertainty 2109:2119 potential uncertainty 2099:2119 potential uncertainty originating from unequal efficiencies in protein digestion in separate vials and retrieval of each labeled peptide 2099:2234 Isotope labeling at the protein level can minimize potential uncertainty originating from unequal efficiencies in protein digestion in separate vials and retrieval of each labeled peptide when labeling takes place at the peptide level. 24960276 7 7 from level 2080:2084 arg1 labeling 2056:2063 Isotope labeling 2048:2063 Isotope labeling at the protein level 2048:2084 Isotope labeling at the protein level can minimize potential uncertainty originating from unequal efficiencies in protein digestion in separate vials and retrieval of each labeled peptide when labeling takes place at the peptide level. 24960276 6 8 gly glycopeptides 1738:1750 arg2 glycopeptides 1738:1750 glycopeptides 1738:1750 glycopeptides with Cys residue 1738:1767 Although iCCM quantitation with mHFER-nLC-MS/MS applies only to glycopeptides with Cys residue, the method can offer several advantages over other labeling methods when applied to targeted glycoproteins: The iCCM method does not require an additional labeling reaction under special conditions nor complicated procedures to purify labeled products using additional columns. 24960276 5 9 with quantitation 1210:1221 arg1 mHFER-nLC-MS/MS 1228:1242 mHFER-nLC-MS/MS 1228:1242 mHFER-nLC-MS/MS 1228:1242 The iCCM quantitation with mHFER-nLC-MS/MS was evaluated with three standard glycoproteins (α-1-acid glycoproteins, fetuin and transferrin) and then applied to serum glycoproteins from liver cancer patients and controls, resulting in successful quantification of 73 N-glycopeptides (from 49 N-glycoproteins), among which 19 N-glycopeptides from 14 N-glycoproteins showed more than a 2.5-fold aberrant change in liver cancer patients' sera compared with the pooled control. 24960276 2 10 theme IAA- 683:686 arg1 D2 694:695 D2 694:695 D2 694:695 The iCCM quantitation uses carbamidomethylation (CM; a routine protection of thiol groups before proteolysis) of the Cys residue of proteins with iodoacetamide (IAA) or its isotope (IAA-(13)C2,D2: 4 Da difference). 24960276 2 10 theme IAA- 683:686 arg1 C2 691:692 IAA-(13)C2 683:692 IAA-(13)C2 683:692 The iCCM quantitation uses carbamidomethylation (CM; a routine protection of thiol groups before proteolysis) of the Cys residue of proteins with iodoacetamide (IAA) or its isotope (IAA-(13)C2,D2: 4 Da difference). 24960276 4 11 theme calculated 1151:1160 arg1 ratio 1162:1166 the calculated ratio 1147:1166 the calculated ratio of light/heavy-labeled peptides 1147:1198 Initial evaluation of the iCCM method varying the mixing ratio of CM-/iCCM-labeled bovine serum albumin (BSA) standards yielded successful quantification of 18 peptides with less than 2% variation in the calculated ratio of light/heavy-labeled peptides. 24960276 5 12 theme N-glycopeptides 1467:1481 arg1 quantification 1446:1459 successful quantification 1435:1459 successful quantification of 73 N-glycopeptides (from 49 N-glycoproteins) 1435:1507 The iCCM quantitation with mHFER-nLC-MS/MS was evaluated with three standard glycoproteins (α-1-acid glycoproteins, fetuin and transferrin) and then applied to serum glycoproteins from liver cancer patients and controls, resulting in successful quantification of 73 N-glycopeptides (from 49 N-glycoproteins), among which 19 N-glycopeptides from 14 N-glycoproteins showed more than a 2.5-fold aberrant change in liver cancer patients' sera compared with the pooled control. 24960276 1 13 theme robust 229:234 arg1 method 259:264 a simple, inexpensive, and robust quantitative proteomic method 202:264 a simple, inexpensive, and robust quantitative proteomic method for quantifying N-linked glycoproteins based on isotope-coded carbamidomethylation (iCCM) incorporated into an online microbore hollow fiber enzyme reactor and nanoflow liquid chromatography-tandem mass spectrometry (mHFER-nLC-MS/MS) 202:498 This paper introduces a simple, inexpensive, and robust quantitative proteomic method for quantifying N-linked glycoproteins based on isotope-coded carbamidomethylation (iCCM) incorporated into an online microbore hollow fiber enzyme reactor and nanoflow liquid chromatography-tandem mass spectrometry (mHFER-nLC-MS/MS). 24960276 7 14 theme protein 2072:2078 arg1 level 2080:2084 the protein level 2068:2084 the protein level 2068:2084 Isotope labeling at the protein level can minimize potential uncertainty originating from unequal efficiencies in protein digestion in separate vials and retrieval of each labeled peptide when labeling takes place at the peptide level. 24960276 2 15 theme proteins 633:640 arg1 proteins 633:640 proteins 633:640 proteins with iodoacetamide (IAA) or its isotope (IAA-(13)C2,D2: 4 Da difference) 633:713 The iCCM quantitation uses carbamidomethylation (CM; a routine protection of thiol groups before proteolysis) of the Cys residue of proteins with iodoacetamide (IAA) or its isotope (IAA-(13)C2,D2: 4 Da difference). 24960276 2 15 theme proteins 633:640 arg1 residue 622:628 the Cys residue 614:628 the Cys residue of proteins with iodoacetamide (IAA) or its isotope (IAA-(13)C2,D2: 4 Da difference) 614:713 The iCCM quantitation uses carbamidomethylation (CM; a routine protection of thiol groups before proteolysis) of the Cys residue of proteins with iodoacetamide (IAA) or its isotope (IAA-(13)C2,D2: 4 Da difference). 24960276 8 16 theme labeling 2301:2308 arg1 reagents 2310:2317 the labeling reagents 2297:2317 the labeling reagents for the iCCM method 2297:2337 In addition, the labeling reagents for the iCCM method are readily obtained at a reasonable cost, which can make protein quantification easily accessible. 24960276 6 17 theme special 1949:1955 arg1 conditions 1957:1966 special conditions 1949:1966 special conditions 1949:1966 Although iCCM quantitation with mHFER-nLC-MS/MS applies only to glycopeptides with Cys residue, the method can offer several advantages over other labeling methods when applied to targeted glycoproteins: The iCCM method does not require an additional labeling reaction under special conditions nor complicated procedures to purify labeled products using additional columns. 24960276 1 18 theme proteomic 249:257 arg1 method 259:264 a simple, inexpensive, and robust quantitative proteomic method 202:264 a simple, inexpensive, and robust quantitative proteomic method for quantifying N-linked glycoproteins based on isotope-coded carbamidomethylation (iCCM) incorporated into an online microbore hollow fiber enzyme reactor and nanoflow liquid chromatography-tandem mass spectrometry (mHFER-nLC-MS/MS) 202:498 This paper introduces a simple, inexpensive, and robust quantitative proteomic method for quantifying N-linked glycoproteins based on isotope-coded carbamidomethylation (iCCM) incorporated into an online microbore hollow fiber enzyme reactor and nanoflow liquid chromatography-tandem mass spectrometry (mHFER-nLC-MS/MS). 24960276 2 19 theme residue 622:628 arg1 CM 550:551 CM 550:551 CM; a routine protection of thiol groups before proteolysis 550:608 The iCCM quantitation uses carbamidomethylation (CM; a routine protection of thiol groups before proteolysis) of the Cys residue of proteins with iodoacetamide (IAA) or its isotope (IAA-(13)C2,D2: 4 Da difference). 24960276 2 19 theme residue 622:628 arg1 carbamidomethylation 528:547 carbamidomethylation 528:547 carbamidomethylation (CM; a routine protection of thiol groups before proteolysis) of the Cys residue of proteins with iodoacetamide (IAA) or its isotope (IAA-(13)C2,D2: 4 Da difference) 528:713 The iCCM quantitation uses carbamidomethylation (CM; a routine protection of thiol groups before proteolysis) of the Cys residue of proteins with iodoacetamide (IAA) or its isotope (IAA-(13)C2,D2: 4 Da difference). 24960276 6 20 with glycopeptides 1738:1750 arg1 residue 1761:1767 Cys residue 1757:1767 Cys residue 1757:1767 Although iCCM quantitation with mHFER-nLC-MS/MS applies only to glycopeptides with Cys residue, the method can offer several advantages over other labeling methods when applied to targeted glycoproteins: The iCCM method does not require an additional labeling reaction under special conditions nor complicated procedures to purify labeled products using additional columns. 24960276 4 21 dep variation 1134:1142 arg1 % 1132:1132 % 1132:1132 % 1132:1132 Initial evaluation of the iCCM method varying the mixing ratio of CM-/iCCM-labeled bovine serum albumin (BSA) standards yielded successful quantification of 18 peptides with less than 2% variation in the calculated ratio of light/heavy-labeled peptides. 24960276 2 22 dep isotope 674:680 arg1 D2 694:695 D2 694:695 D2 694:695 The iCCM quantitation uses carbamidomethylation (CM; a routine protection of thiol groups before proteolysis) of the Cys residue of proteins with iodoacetamide (IAA) or its isotope (IAA-(13)C2,D2: 4 Da difference). 24960276 2 22 dep isotope 674:680 arg1 C2 691:692 IAA-(13)C2 683:692 IAA-(13)C2 683:692 The iCCM quantitation uses carbamidomethylation (CM; a routine protection of thiol groups before proteolysis) of the Cys residue of proteins with iodoacetamide (IAA) or its isotope (IAA-(13)C2,D2: 4 Da difference). 24960276 5 23 from N-glycoproteins 1549:1563 arg1 N-glycopeptides 1525:1539 19 N-glycopeptides 1522:1539 19 N-glycopeptides from 14 N-glycoproteins 1522:1563 The iCCM quantitation with mHFER-nLC-MS/MS was evaluated with three standard glycoproteins (α-1-acid glycoproteins, fetuin and transferrin) and then applied to serum glycoproteins from liver cancer patients and controls, resulting in successful quantification of 73 N-glycopeptides (from 49 N-glycoproteins), among which 19 N-glycopeptides from 14 N-glycoproteins showed more than a 2.5-fold aberrant change in liver cancer patients' sera compared with the pooled control. 24960276 8 24 theme iCCM 2327:2330 arg1 method 2332:2337 the iCCM method 2323:2337 the iCCM method 2323:2337 In addition, the labeling reagents for the iCCM method are readily obtained at a reasonable cost, which can make protein quantification easily accessible. 24960276 3 25 theme online 783:788 arg1 enrichment 790:799 online enrichment 783:799 online enrichment of N-glycopeptides using lectin affinity 783:840 CM-/iCCM-labeled proteome samples are mixed for proteolysis; then, online enrichment of N-glycopeptides using lectin affinity is carried out in an mHFER before nLC-MS/MS for quantification using multiple reaction monitoring (MRM). 24960276 6 26 theme additional 2028:2037 arg1 columns 2039:2045 additional columns 2028:2045 additional columns 2028:2045 Although iCCM quantitation with mHFER-nLC-MS/MS applies only to glycopeptides with Cys residue, the method can offer several advantages over other labeling methods when applied to targeted glycoproteins: The iCCM method does not require an additional labeling reaction under special conditions nor complicated procedures to purify labeled products using additional columns. 24960276 4 27 theme mixing 997:1002 arg1 ratio 1004:1008 the mixing ratio 993:1008 the mixing ratio of CM-/iCCM-labeled bovine serum albumin (BSA) standards 993:1065 Initial evaluation of the iCCM method varying the mixing ratio of CM-/iCCM-labeled bovine serum albumin (BSA) standards yielded successful quantification of 18 peptides with less than 2% variation in the calculated ratio of light/heavy-labeled peptides. 24960276 7 28 theme separate 2183:2190 arg1 vials 2192:2196 separate vials 2183:2196 separate vials 2183:2196 Isotope labeling at the protein level can minimize potential uncertainty originating from unequal efficiencies in protein digestion in separate vials and retrieval of each labeled peptide when labeling takes place at the peptide level. 24960276 1 29 theme fiber 401:405 arg1 reactor 414:420 an online microbore hollow fiber enzyme reactor 374:420 an online microbore hollow fiber enzyme reactor 374:420 This paper introduces a simple, inexpensive, and robust quantitative proteomic method for quantifying N-linked glycoproteins based on isotope-coded carbamidomethylation (iCCM) incorporated into an online microbore hollow fiber enzyme reactor and nanoflow liquid chromatography-tandem mass spectrometry (mHFER-nLC-MS/MS). 24960276 3 30 theme multiple 911:918 arg1 MRM 941:943 MRM 941:943 MRM 941:943 CM-/iCCM-labeled proteome samples are mixed for proteolysis; then, online enrichment of N-glycopeptides using lectin affinity is carried out in an mHFER before nLC-MS/MS for quantification using multiple reaction monitoring (MRM). 24960276 3 30 theme multiple 911:918 arg1 monitoring 929:938 multiple reaction monitoring 911:938 multiple reaction monitoring (MRM) 911:944 CM-/iCCM-labeled proteome samples are mixed for proteolysis; then, online enrichment of N-glycopeptides using lectin affinity is carried out in an mHFER before nLC-MS/MS for quantification using multiple reaction monitoring (MRM). 24960276 2 31 theme thiol 578:582 arg1 groups 584:589 thiol groups 578:589 thiol groups before proteolysis 578:608 The iCCM quantitation uses carbamidomethylation (CM; a routine protection of thiol groups before proteolysis) of the Cys residue of proteins with iodoacetamide (IAA) or its isotope (IAA-(13)C2,D2: 4 Da difference). 24960276 4 32 theme peptides 1191:1198 arg1 ratio 1162:1166 the calculated ratio 1147:1166 the calculated ratio of light/heavy-labeled peptides 1147:1198 Initial evaluation of the iCCM method varying the mixing ratio of CM-/iCCM-labeled bovine serum albumin (BSA) standards yielded successful quantification of 18 peptides with less than 2% variation in the calculated ratio of light/heavy-labeled peptides. 24960276 0 33 theme fiber 102:106 arg1 spectrometry 166:177 hollow fiber enzyme reactor-nanoflow liquid chromatography-tandem mass spectrometry 95:177 hollow fiber enzyme reactor-nanoflow liquid chromatography-tandem mass spectrometry 95:177 Isotope-coded carbamidomethylation for quantification of N-glycoproteins with online microbore hollow fiber enzyme reactor-nanoflow liquid chromatography-tandem mass spectrometry. 24960276 7 34 from digestion 2170:2178 arg1 vials 2192:2196 separate vials 2183:2196 separate vials 2183:2196 Isotope labeling at the protein level can minimize potential uncertainty originating from unequal efficiencies in protein digestion in separate vials and retrieval of each labeled peptide when labeling takes place at the peptide level. 24960276 4 35 theme iCCM 973:976 arg1 method 978:983 the iCCM method 969:983 the iCCM method varying the mixing ratio of CM-/iCCM-labeled bovine serum albumin (BSA) standards 969:1065 Initial evaluation of the iCCM method varying the mixing ratio of CM-/iCCM-labeled bovine serum albumin (BSA) standards yielded successful quantification of 18 peptides with less than 2% variation in the calculated ratio of light/heavy-labeled peptides. 24960276 6 36 theme several 1791:1797 arg1 advantages 1799:1808 several advantages 1791:1808 several advantages over other labeling methods 1791:1836 Although iCCM quantitation with mHFER-nLC-MS/MS applies only to glycopeptides with Cys residue, the method can offer several advantages over other labeling methods when applied to targeted glycoproteins: The iCCM method does not require an additional labeling reaction under special conditions nor complicated procedures to purify labeled products using additional columns. 24960276 0 37 theme reactor-nanoflow 115:130 arg1 spectrometry 166:177 hollow fiber enzyme reactor-nanoflow liquid chromatography-tandem mass spectrometry 95:177 hollow fiber enzyme reactor-nanoflow liquid chromatography-tandem mass spectrometry 95:177 Isotope-coded carbamidomethylation for quantification of N-glycoproteins with online microbore hollow fiber enzyme reactor-nanoflow liquid chromatography-tandem mass spectrometry. 24960276 1 38 theme nanoflow 426:433 arg1 mHFER-nLC-MS/MS 483:497 mHFER-nLC-MS/MS 483:497 mHFER-nLC-MS/MS 483:497 This paper introduces a simple, inexpensive, and robust quantitative proteomic method for quantifying N-linked glycoproteins based on isotope-coded carbamidomethylation (iCCM) incorporated into an online microbore hollow fiber enzyme reactor and nanoflow liquid chromatography-tandem mass spectrometry (mHFER-nLC-MS/MS). 24960276 1 38 theme nanoflow 426:433 arg1 spectrometry 469:480 nanoflow liquid chromatography-tandem mass spectrometry 426:480 nanoflow liquid chromatography-tandem mass spectrometry (mHFER-nLC-MS/MS) 426:498 This paper introduces a simple, inexpensive, and robust quantitative proteomic method for quantifying N-linked glycoproteins based on isotope-coded carbamidomethylation (iCCM) incorporated into an online microbore hollow fiber enzyme reactor and nanoflow liquid chromatography-tandem mass spectrometry (mHFER-nLC-MS/MS). 24960276 5 39 gly glycoproteins 1278:1290 arg1 glycoproteins 1278:1290 three standard glycoproteins 1263:1290 three standard glycoproteins (α-1-acid glycoproteins, fetuin and transferrin) 1263:1339 The iCCM quantitation with mHFER-nLC-MS/MS was evaluated with three standard glycoproteins (α-1-acid glycoproteins, fetuin and transferrin) and then applied to serum glycoproteins from liver cancer patients and controls, resulting in successful quantification of 73 N-glycopeptides (from 49 N-glycoproteins), among which 19 N-glycopeptides from 14 N-glycoproteins showed more than a 2.5-fold aberrant change in liver cancer patients' sera compared with the pooled control. 24960276 0 40 theme chromatography-tandem 139:159 arg1 spectrometry 166:177 hollow fiber enzyme reactor-nanoflow liquid chromatography-tandem mass spectrometry 95:177 hollow fiber enzyme reactor-nanoflow liquid chromatography-tandem mass spectrometry 95:177 Isotope-coded carbamidomethylation for quantification of N-glycoproteins with online microbore hollow fiber enzyme reactor-nanoflow liquid chromatography-tandem mass spectrometry. 24960276 1 41 theme chromatography-tandem 442:462 arg1 mHFER-nLC-MS/MS 483:497 mHFER-nLC-MS/MS 483:497 mHFER-nLC-MS/MS 483:497 This paper introduces a simple, inexpensive, and robust quantitative proteomic method for quantifying N-linked glycoproteins based on isotope-coded carbamidomethylation (iCCM) incorporated into an online microbore hollow fiber enzyme reactor and nanoflow liquid chromatography-tandem mass spectrometry (mHFER-nLC-MS/MS). 24960276 1 41 theme chromatography-tandem 442:462 arg1 spectrometry 469:480 nanoflow liquid chromatography-tandem mass spectrometry 426:480 nanoflow liquid chromatography-tandem mass spectrometry (mHFER-nLC-MS/MS) 426:498 This paper introduces a simple, inexpensive, and robust quantitative proteomic method for quantifying N-linked glycoproteins based on isotope-coded carbamidomethylation (iCCM) incorporated into an online microbore hollow fiber enzyme reactor and nanoflow liquid chromatography-tandem mass spectrometry (mHFER-nLC-MS/MS). 24960276 2 42 theme Da 700:701 arg1 difference 703:712 4 Da difference 698:712 4 Da difference 698:712 The iCCM quantitation uses carbamidomethylation (CM; a routine protection of thiol groups before proteolysis) of the Cys residue of proteins with iodoacetamide (IAA) or its isotope (IAA-(13)C2,D2: 4 Da difference). 24960276 5 43 theme cancer 1392:1397 arg1 patients 1399:1406 liver cancer patients 1386:1406 liver cancer patients 1386:1406 The iCCM quantitation with mHFER-nLC-MS/MS was evaluated with three standard glycoproteins (α-1-acid glycoproteins, fetuin and transferrin) and then applied to serum glycoproteins from liver cancer patients and controls, resulting in successful quantification of 73 N-glycopeptides (from 49 N-glycoproteins), among which 19 N-glycopeptides from 14 N-glycoproteins showed more than a 2.5-fold aberrant change in liver cancer patients' sera compared with the pooled control. 24960276 5 44 gly N-glycoproteins 1549:1563 arg1 N-glycoproteins 1549:1563 14 N-glycoproteins 1546:1563 14 N-glycoproteins 1546:1563 The iCCM quantitation with mHFER-nLC-MS/MS was evaluated with three standard glycoproteins (α-1-acid glycoproteins, fetuin and transferrin) and then applied to serum glycoproteins from liver cancer patients and controls, resulting in successful quantification of 73 N-glycopeptides (from 49 N-glycoproteins), among which 19 N-glycopeptides from 14 N-glycoproteins showed more than a 2.5-fold aberrant change in liver cancer patients' sera compared with the pooled control. 24960276 0 45 theme Isotope-coded 0:12 arg1 carbamidomethylation 14:33 Isotope-coded carbamidomethylation 0:33 Isotope-coded carbamidomethylation for quantification of N-glycoproteins with online 0:83 Isotope-coded carbamidomethylation for quantification of N-glycoproteins with online microbore hollow fiber enzyme reactor-nanoflow liquid chromatography-tandem mass spectrometry. 24960276 4 46 theme standards 1057:1065 arg1 ratio 1004:1008 the mixing ratio 993:1008 the mixing ratio of CM-/iCCM-labeled bovine serum albumin (BSA) standards 993:1065 Initial evaluation of the iCCM method varying the mixing ratio of CM-/iCCM-labeled bovine serum albumin (BSA) standards yielded successful quantification of 18 peptides with less than 2% variation in the calculated ratio of light/heavy-labeled peptides. 24960276 5 47 theme 2.5-fold 1584:1591 arg1 change 1602:1607 a 2.5-fold aberrant change 1582:1607 a 2.5-fold aberrant change in liver cancer patients' sera 1582:1638 The iCCM quantitation with mHFER-nLC-MS/MS was evaluated with three standard glycoproteins (α-1-acid glycoproteins, fetuin and transferrin) and then applied to serum glycoproteins from liver cancer patients and controls, resulting in successful quantification of 73 N-glycopeptides (from 49 N-glycoproteins), among which 19 N-glycopeptides from 14 N-glycoproteins showed more than a 2.5-fold aberrant change in liver cancer patients' sera compared with the pooled control. 24960276 5 48 from quantification 1446:1459 arg1 N-glycoproteins 1492:1506 49 N-glycoproteins 1489:1506 49 N-glycoproteins 1489:1506 The iCCM quantitation with mHFER-nLC-MS/MS was evaluated with three standard glycoproteins (α-1-acid glycoproteins, fetuin and transferrin) and then applied to serum glycoproteins from liver cancer patients and controls, resulting in successful quantification of 73 N-glycopeptides (from 49 N-glycoproteins), among which 19 N-glycopeptides from 14 N-glycoproteins showed more than a 2.5-fold aberrant change in liver cancer patients' sera compared with the pooled control. 24960276 4 49 theme bovine 1030:1035 arg1 BSA 1052:1054 BSA 1052:1054 BSA 1052:1054 Initial evaluation of the iCCM method varying the mixing ratio of CM-/iCCM-labeled bovine serum albumin (BSA) standards yielded successful quantification of 18 peptides with less than 2% variation in the calculated ratio of light/heavy-labeled peptides. 24960276 4 49 theme bovine 1030:1035 arg1 albumin 1043:1049 bovine serum albumin 1030:1049 CM-/iCCM-labeled bovine serum albumin (BSA) standards 1013:1065 Initial evaluation of the iCCM method varying the mixing ratio of CM-/iCCM-labeled bovine serum albumin (BSA) standards yielded successful quantification of 18 peptides with less than 2% variation in the calculated ratio of light/heavy-labeled peptides. 24960276 5 50 theme serum 1361:1365 arg1 glycoproteins 1367:1379 serum glycoproteins 1361:1379 serum glycoproteins 1361:1379 The iCCM quantitation with mHFER-nLC-MS/MS was evaluated with three standard glycoproteins (α-1-acid glycoproteins, fetuin and transferrin) and then applied to serum glycoproteins from liver cancer patients and controls, resulting in successful quantification of 73 N-glycopeptides (from 49 N-glycoproteins), among which 19 N-glycopeptides from 14 N-glycoproteins showed more than a 2.5-fold aberrant change in liver cancer patients' sera compared with the pooled control. 24960276 2 51 theme routine 556:562 arg1 protection 564:573 a routine protection 554:573 CM; a routine protection of thiol groups before proteolysis 550:608 The iCCM quantitation uses carbamidomethylation (CM; a routine protection of thiol groups before proteolysis) of the Cys residue of proteins with iodoacetamide (IAA) or its isotope (IAA-(13)C2,D2: 4 Da difference). 24960276 4 52 theme albumin 1043:1049 arg1 standards 1057:1065 CM-/iCCM-labeled bovine serum albumin (BSA) standards 1013:1065 CM-/iCCM-labeled bovine serum albumin (BSA) standards 1013:1065 Initial evaluation of the iCCM method varying the mixing ratio of CM-/iCCM-labeled bovine serum albumin (BSA) standards yielded successful quantification of 18 peptides with less than 2% variation in the calculated ratio of light/heavy-labeled peptides. 24960276 1 53 theme microbore 384:392 arg1 reactor 414:420 an online microbore hollow fiber enzyme reactor 374:420 an online microbore hollow fiber enzyme reactor 374:420 This paper introduces a simple, inexpensive, and robust quantitative proteomic method for quantifying N-linked glycoproteins based on isotope-coded carbamidomethylation (iCCM) incorporated into an online microbore hollow fiber enzyme reactor and nanoflow liquid chromatography-tandem mass spectrometry (mHFER-nLC-MS/MS). 24960276 6 54 theme other 1815:1819 arg1 methods 1830:1836 other labeling methods 1815:1836 other labeling methods 1815:1836 Although iCCM quantitation with mHFER-nLC-MS/MS applies only to glycopeptides with Cys residue, the method can offer several advantages over other labeling methods when applied to targeted glycoproteins: The iCCM method does not require an additional labeling reaction under special conditions nor complicated procedures to purify labeled products using additional columns. 24960276 4 55 theme peptides 1107:1114 arg1 quantification 1086:1099 successful quantification 1075:1099 successful quantification of 18 peptides 1075:1114 Initial evaluation of the iCCM method varying the mixing ratio of CM-/iCCM-labeled bovine serum albumin (BSA) standards yielded successful quantification of 18 peptides with less than 2% variation in the calculated ratio of light/heavy-labeled peptides. 24960276 6 56 theme labeling 1821:1828 arg1 methods 1830:1836 other labeling methods 1815:1836 other labeling methods 1815:1836 Although iCCM quantitation with mHFER-nLC-MS/MS applies only to glycopeptides with Cys residue, the method can offer several advantages over other labeling methods when applied to targeted glycoproteins: The iCCM method does not require an additional labeling reaction under special conditions nor complicated procedures to purify labeled products using additional columns. 24960276 0 57 gly N-glycoproteins 57:71 arg1 N-glycoproteins 57:71 N-glycoproteins 57:71 N-glycoproteins 57:71 Isotope-coded carbamidomethylation for quantification of N-glycoproteins with online microbore hollow fiber enzyme reactor-nanoflow liquid chromatography-tandem mass spectrometry. 24960276 7 58 theme peptide 2269:2275 arg1 level 2277:2281 the peptide level 2265:2281 the peptide level 2265:2281 Isotope labeling at the protein level can minimize potential uncertainty originating from unequal efficiencies in protein digestion in separate vials and retrieval of each labeled peptide when labeling takes place at the peptide level. 24960276 2 59 dep C2 691:692 arg1 difference 703:712 4 Da difference 698:712 4 Da difference 698:712 The iCCM quantitation uses carbamidomethylation (CM; a routine protection of thiol groups before proteolysis) of the Cys residue of proteins with iodoacetamide (IAA) or its isotope (IAA-(13)C2,D2: 4 Da difference). 24960276 7 60 theme protein 2162:2168 arg1 digestion 2170:2178 protein digestion 2162:2178 protein digestion in separate vials 2162:2196 Isotope labeling at the protein level can minimize potential uncertainty originating from unequal efficiencies in protein digestion in separate vials and retrieval of each labeled peptide when labeling takes place at the peptide level. 24960276 3 61 theme lectin 826:831 arg1 affinity 833:840 lectin affinity 826:840 lectin affinity 826:840 CM-/iCCM-labeled proteome samples are mixed for proteolysis; then, online enrichment of N-glycopeptides using lectin affinity is carried out in an mHFER before nLC-MS/MS for quantification using multiple reaction monitoring (MRM). 24960276 4 62 theme successful 1075:1084 arg1 quantification 1086:1099 successful quantification 1075:1099 successful quantification of 18 peptides 1075:1114 Initial evaluation of the iCCM method varying the mixing ratio of CM-/iCCM-labeled bovine serum albumin (BSA) standards yielded successful quantification of 18 peptides with less than 2% variation in the calculated ratio of light/heavy-labeled peptides. 24960276 5 63 gly glycoproteins 1367:1379 arg1 glycoproteins 1367:1379 serum glycoproteins 1361:1379 serum glycoproteins 1361:1379 The iCCM quantitation with mHFER-nLC-MS/MS was evaluated with three standard glycoproteins (α-1-acid glycoproteins, fetuin and transferrin) and then applied to serum glycoproteins from liver cancer patients and controls, resulting in successful quantification of 73 N-glycopeptides (from 49 N-glycoproteins), among which 19 N-glycopeptides from 14 N-glycoproteins showed more than a 2.5-fold aberrant change in liver cancer patients' sera compared with the pooled control. 24960276 8 64 theme accessible 2427:2436 arg1 quantification 2405:2418 protein quantification 2397:2418 protein quantification easily accessible 2397:2436 In addition, the labeling reagents for the iCCM method are readily obtained at a reasonable cost, which can make protein quantification easily accessible. 24960276 5 65 theme liver 1612:1616 arg1 sera 1635:1638 liver cancer patients' sera 1612:1638 liver cancer patients' sera 1612:1638 The iCCM quantitation with mHFER-nLC-MS/MS was evaluated with three standard glycoproteins (α-1-acid glycoproteins, fetuin and transferrin) and then applied to serum glycoproteins from liver cancer patients and controls, resulting in successful quantification of 73 N-glycopeptides (from 49 N-glycoproteins), among which 19 N-glycopeptides from 14 N-glycoproteins showed more than a 2.5-fold aberrant change in liver cancer patients' sera compared with the pooled control. 24960276 1 66 theme inexpensive 212:222 arg1 method 259:264 a simple, inexpensive, and robust quantitative proteomic method 202:264 a simple, inexpensive, and robust quantitative proteomic method for quantifying N-linked glycoproteins based on isotope-coded carbamidomethylation (iCCM) incorporated into an online microbore hollow fiber enzyme reactor and nanoflow liquid chromatography-tandem mass spectrometry (mHFER-nLC-MS/MS) 202:498 This paper introduces a simple, inexpensive, and robust quantitative proteomic method for quantifying N-linked glycoproteins based on isotope-coded carbamidomethylation (iCCM) incorporated into an online microbore hollow fiber enzyme reactor and nanoflow liquid chromatography-tandem mass spectrometry (mHFER-nLC-MS/MS). 24960276 6 67 theme complicated 1972:1982 arg1 procedures 1984:1993 complicated procedures 1972:1993 complicated procedures 1972:1993 Although iCCM quantitation with mHFER-nLC-MS/MS applies only to glycopeptides with Cys residue, the method can offer several advantages over other labeling methods when applied to targeted glycoproteins: The iCCM method does not require an additional labeling reaction under special conditions nor complicated procedures to purify labeled products using additional columns. 24960276 1 68 link N-linked 282:289 arg1 glycoproteins 291:303 N-linked glycoproteins 282:303 N-linked glycoproteins based on isotope-coded carbamidomethylation (iCCM) incorporated into an online microbore hollow fiber enzyme reactor and nanoflow liquid chromatography-tandem mass spectrometry (mHFER-nLC-MS/MS) 282:498 This paper introduces a simple, inexpensive, and robust quantitative proteomic method for quantifying N-linked glycoproteins based on isotope-coded carbamidomethylation (iCCM) incorporated into an online microbore hollow fiber enzyme reactor and nanoflow liquid chromatography-tandem mass spectrometry (mHFER-nLC-MS/MS). 24960276 1 69 theme quantitative 236:247 arg1 method 259:264 a simple, inexpensive, and robust quantitative proteomic method 202:264 a simple, inexpensive, and robust quantitative proteomic method for quantifying N-linked glycoproteins based on isotope-coded carbamidomethylation (iCCM) incorporated into an online microbore hollow fiber enzyme reactor and nanoflow liquid chromatography-tandem mass spectrometry (mHFER-nLC-MS/MS) 202:498 This paper introduces a simple, inexpensive, and robust quantitative proteomic method for quantifying N-linked glycoproteins based on isotope-coded carbamidomethylation (iCCM) incorporated into an online microbore hollow fiber enzyme reactor and nanoflow liquid chromatography-tandem mass spectrometry (mHFER-nLC-MS/MS). 24960276 0 70 with carbamidomethylation 14:33 arg1 online 78:83 online 78:83 online 78:83 Isotope-coded carbamidomethylation for quantification of N-glycoproteins with online microbore hollow fiber enzyme reactor-nanoflow liquid chromatography-tandem mass spectrometry. 24960276 5 71 dep glycoproteins 1278:1290 arg1 transferrin 1328:1338 transferrin 1328:1338 transferrin 1328:1338 The iCCM quantitation with mHFER-nLC-MS/MS was evaluated with three standard glycoproteins (α-1-acid glycoproteins, fetuin and transferrin) and then applied to serum glycoproteins from liver cancer patients and controls, resulting in successful quantification of 73 N-glycopeptides (from 49 N-glycoproteins), among which 19 N-glycopeptides from 14 N-glycoproteins showed more than a 2.5-fold aberrant change in liver cancer patients' sera compared with the pooled control. 24960276 5 71 dep glycoproteins 1278:1290 arg1 fetuin 1317:1322 fetuin 1317:1322 fetuin 1317:1322 The iCCM quantitation with mHFER-nLC-MS/MS was evaluated with three standard glycoproteins (α-1-acid glycoproteins, fetuin and transferrin) and then applied to serum glycoproteins from liver cancer patients and controls, resulting in successful quantification of 73 N-glycopeptides (from 49 N-glycoproteins), among which 19 N-glycopeptides from 14 N-glycoproteins showed more than a 2.5-fold aberrant change in liver cancer patients' sera compared with the pooled control. 24960276 5 71 dep glycoproteins 1278:1290 arg1 glycoproteins 1302:1314 α-1-acid glycoproteins 1293:1314 α-1-acid glycoproteins 1293:1314 The iCCM quantitation with mHFER-nLC-MS/MS was evaluated with three standard glycoproteins (α-1-acid glycoproteins, fetuin and transferrin) and then applied to serum glycoproteins from liver cancer patients and controls, resulting in successful quantification of 73 N-glycopeptides (from 49 N-glycoproteins), among which 19 N-glycopeptides from 14 N-glycoproteins showed more than a 2.5-fold aberrant change in liver cancer patients' sera compared with the pooled control. 24960276 5 72 theme pooled 1658:1663 arg1 control 1665:1671 the pooled control 1654:1671 the pooled control 1654:1671 The iCCM quantitation with mHFER-nLC-MS/MS was evaluated with three standard glycoproteins (α-1-acid glycoproteins, fetuin and transferrin) and then applied to serum glycoproteins from liver cancer patients and controls, resulting in successful quantification of 73 N-glycopeptides (from 49 N-glycoproteins), among which 19 N-glycopeptides from 14 N-glycoproteins showed more than a 2.5-fold aberrant change in liver cancer patients' sera compared with the pooled control. 24960276 2 73 theme Cys 618:620 arg1 proteins 633:640 proteins 633:640 proteins with iodoacetamide (IAA) or its isotope (IAA-(13)C2,D2: 4 Da difference) 633:713 The iCCM quantitation uses carbamidomethylation (CM; a routine protection of thiol groups before proteolysis) of the Cys residue of proteins with iodoacetamide (IAA) or its isotope (IAA-(13)C2,D2: 4 Da difference). 24960276 2 73 theme Cys 618:620 arg1 residue 622:628 the Cys residue 614:628 the Cys residue of proteins with iodoacetamide (IAA) or its isotope (IAA-(13)C2,D2: 4 Da difference) 614:713 The iCCM quantitation uses carbamidomethylation (CM; a routine protection of thiol groups before proteolysis) of the Cys residue of proteins with iodoacetamide (IAA) or its isotope (IAA-(13)C2,D2: 4 Da difference). 24960276 6 74 theme Cys 1757:1759 arg1 residue 1761:1767 Cys residue 1757:1767 Cys residue 1757:1767 Although iCCM quantitation with mHFER-nLC-MS/MS applies only to glycopeptides with Cys residue, the method can offer several advantages over other labeling methods when applied to targeted glycoproteins: The iCCM method does not require an additional labeling reaction under special conditions nor complicated procedures to purify labeled products using additional columns. 24960276 6 75 theme labeling 1925:1932 arg1 reaction 1934:1941 an additional labeling reaction 1911:1941 an additional labeling reaction under special conditions nor complicated procedures to purify labeled products using additional columns 1911:2045 Although iCCM quantitation with mHFER-nLC-MS/MS applies only to glycopeptides with Cys residue, the method can offer several advantages over other labeling methods when applied to targeted glycoproteins: The iCCM method does not require an additional labeling reaction under special conditions nor complicated procedures to purify labeled products using additional columns. 24960276 3 76 theme N-glycopeptides 804:818 arg1 enrichment 790:799 online enrichment 783:799 online enrichment of N-glycopeptides using lectin affinity 783:840 CM-/iCCM-labeled proteome samples are mixed for proteolysis; then, online enrichment of N-glycopeptides using lectin affinity is carried out in an mHFER before nLC-MS/MS for quantification using multiple reaction monitoring (MRM). 24960276 4 77 dep % 1132:1132 arg1 2 1131:1131 2 1131:1131 2 1131:1131 Initial evaluation of the iCCM method varying the mixing ratio of CM-/iCCM-labeled bovine serum albumin (BSA) standards yielded successful quantification of 18 peptides with less than 2% variation in the calculated ratio of light/heavy-labeled peptides. 24960276 4 78 theme Initial 947:953 arg1 evaluation 955:964 Initial evaluation 947:964 Initial evaluation of the iCCM method varying the mixing ratio of CM-/iCCM-labeled bovine serum albumin (BSA) standards 947:1065 Initial evaluation of the iCCM method varying the mixing ratio of CM-/iCCM-labeled bovine serum albumin (BSA) standards yielded successful quantification of 18 peptides with less than 2% variation in the calculated ratio of light/heavy-labeled peptides. 24960276 4 79 theme light/heavy-labeled 1171:1189 arg1 peptides 1191:1198 light/heavy-labeled peptides 1171:1198 light/heavy-labeled peptides 1171:1198 Initial evaluation of the iCCM method varying the mixing ratio of CM-/iCCM-labeled bovine serum albumin (BSA) standards yielded successful quantification of 18 peptides with less than 2% variation in the calculated ratio of light/heavy-labeled peptides. 24960276 0 80 theme hollow 95:100 arg1 spectrometry 166:177 hollow fiber enzyme reactor-nanoflow liquid chromatography-tandem mass spectrometry 95:177 hollow fiber enzyme reactor-nanoflow liquid chromatography-tandem mass spectrometry 95:177 Isotope-coded carbamidomethylation for quantification of N-glycoproteins with online microbore hollow fiber enzyme reactor-nanoflow liquid chromatography-tandem mass spectrometry. 24960276 4 81 from variation 1134:1142 arg1 ratio 1162:1166 the calculated ratio 1147:1166 the calculated ratio of light/heavy-labeled peptides 1147:1198 Initial evaluation of the iCCM method varying the mixing ratio of CM-/iCCM-labeled bovine serum albumin (BSA) standards yielded successful quantification of 18 peptides with less than 2% variation in the calculated ratio of light/heavy-labeled peptides. 24960276 2 82 theme groups 584:589 arg1 protection 564:573 a routine protection 554:573 CM; a routine protection of thiol groups before proteolysis 550:608 The iCCM quantitation uses carbamidomethylation (CM; a routine protection of thiol groups before proteolysis) of the Cys residue of proteins with iodoacetamide (IAA) or its isotope (IAA-(13)C2,D2: 4 Da difference). 24960276 3 83 gly N-glycopeptides 804:818 arg2 N-glycopeptides 804:818 N-glycopeptides 804:818 N-glycopeptides using lectin affinity 804:840 CM-/iCCM-labeled proteome samples are mixed for proteolysis; then, online enrichment of N-glycopeptides using lectin affinity is carried out in an mHFER before nLC-MS/MS for quantification using multiple reaction monitoring (MRM). 24960276 6 84 theme labeled 2005:2011 arg1 products 2013:2020 labeled products 2005:2020 labeled products using additional columns 2005:2045 Although iCCM quantitation with mHFER-nLC-MS/MS applies only to glycopeptides with Cys residue, the method can offer several advantages over other labeling methods when applied to targeted glycoproteins: The iCCM method does not require an additional labeling reaction under special conditions nor complicated procedures to purify labeled products using additional columns. 24960276 5 85 theme α-1-acid 1293:1300 arg1 transferrin 1328:1338 transferrin 1328:1338 transferrin 1328:1338 The iCCM quantitation with mHFER-nLC-MS/MS was evaluated with three standard glycoproteins (α-1-acid glycoproteins, fetuin and transferrin) and then applied to serum glycoproteins from liver cancer patients and controls, resulting in successful quantification of 73 N-glycopeptides (from 49 N-glycoproteins), among which 19 N-glycopeptides from 14 N-glycoproteins showed more than a 2.5-fold aberrant change in liver cancer patients' sera compared with the pooled control. 24960276 5 85 theme α-1-acid 1293:1300 arg1 fetuin 1317:1322 fetuin 1317:1322 fetuin 1317:1322 The iCCM quantitation with mHFER-nLC-MS/MS was evaluated with three standard glycoproteins (α-1-acid glycoproteins, fetuin and transferrin) and then applied to serum glycoproteins from liver cancer patients and controls, resulting in successful quantification of 73 N-glycopeptides (from 49 N-glycoproteins), among which 19 N-glycopeptides from 14 N-glycoproteins showed more than a 2.5-fold aberrant change in liver cancer patients' sera compared with the pooled control. 24960276 5 85 theme α-1-acid 1293:1300 arg1 glycoproteins 1302:1314 α-1-acid glycoproteins 1293:1314 α-1-acid glycoproteins 1293:1314 The iCCM quantitation with mHFER-nLC-MS/MS was evaluated with three standard glycoproteins (α-1-acid glycoproteins, fetuin and transferrin) and then applied to serum glycoproteins from liver cancer patients and controls, resulting in successful quantification of 73 N-glycopeptides (from 49 N-glycoproteins), among which 19 N-glycopeptides from 14 N-glycoproteins showed more than a 2.5-fold aberrant change in liver cancer patients' sera compared with the pooled control. 24960276 5 86 gly N-glycoproteins 1492:1506 arg1 N-glycoproteins 1492:1506 49 N-glycoproteins 1489:1506 49 N-glycoproteins 1489:1506 The iCCM quantitation with mHFER-nLC-MS/MS was evaluated with three standard glycoproteins (α-1-acid glycoproteins, fetuin and transferrin) and then applied to serum glycoproteins from liver cancer patients and controls, resulting in successful quantification of 73 N-glycopeptides (from 49 N-glycoproteins), among which 19 N-glycopeptides from 14 N-glycoproteins showed more than a 2.5-fold aberrant change in liver cancer patients' sera compared with the pooled control. 24960276 0 87 theme enzyme 108:113 arg1 spectrometry 166:177 hollow fiber enzyme reactor-nanoflow liquid chromatography-tandem mass spectrometry 95:177 hollow fiber enzyme reactor-nanoflow liquid chromatography-tandem mass spectrometry 95:177 Isotope-coded carbamidomethylation for quantification of N-glycoproteins with online microbore hollow fiber enzyme reactor-nanoflow liquid chromatography-tandem mass spectrometry. 24960276 1 88 theme enzyme 407:412 arg1 reactor 414:420 an online microbore hollow fiber enzyme reactor 374:420 an online microbore hollow fiber enzyme reactor 374:420 This paper introduces a simple, inexpensive, and robust quantitative proteomic method for quantifying N-linked glycoproteins based on isotope-coded carbamidomethylation (iCCM) incorporated into an online microbore hollow fiber enzyme reactor and nanoflow liquid chromatography-tandem mass spectrometry (mHFER-nLC-MS/MS). 24960276 1 89 theme simple 204:209 arg1 method 259:264 a simple, inexpensive, and robust quantitative proteomic method 202:264 a simple, inexpensive, and robust quantitative proteomic method for quantifying N-linked glycoproteins based on isotope-coded carbamidomethylation (iCCM) incorporated into an online microbore hollow fiber enzyme reactor and nanoflow liquid chromatography-tandem mass spectrometry (mHFER-nLC-MS/MS) 202:498 This paper introduces a simple, inexpensive, and robust quantitative proteomic method for quantifying N-linked glycoproteins based on isotope-coded carbamidomethylation (iCCM) incorporated into an online microbore hollow fiber enzyme reactor and nanoflow liquid chromatography-tandem mass spectrometry (mHFER-nLC-MS/MS). 24960276 3 90 theme reaction 920:927 arg1 MRM 941:943 MRM 941:943 MRM 941:943 CM-/iCCM-labeled proteome samples are mixed for proteolysis; then, online enrichment of N-glycopeptides using lectin affinity is carried out in an mHFER before nLC-MS/MS for quantification using multiple reaction monitoring (MRM). 24960276 3 90 theme reaction 920:927 arg1 monitoring 929:938 multiple reaction monitoring 911:938 multiple reaction monitoring (MRM) 911:944 CM-/iCCM-labeled proteome samples are mixed for proteolysis; then, online enrichment of N-glycopeptides using lectin affinity is carried out in an mHFER before nLC-MS/MS for quantification using multiple reaction monitoring (MRM). 24960276 5 91 from change 1602:1607 arg1 sera 1635:1638 liver cancer patients' sera 1612:1638 liver cancer patients' sera 1612:1638 The iCCM quantitation with mHFER-nLC-MS/MS was evaluated with three standard glycoproteins (α-1-acid glycoproteins, fetuin and transferrin) and then applied to serum glycoproteins from liver cancer patients and controls, resulting in successful quantification of 73 N-glycopeptides (from 49 N-glycoproteins), among which 19 N-glycopeptides from 14 N-glycoproteins showed more than a 2.5-fold aberrant change in liver cancer patients' sera compared with the pooled control. 24960276 0 92 theme liquid 132:137 arg1 spectrometry 166:177 hollow fiber enzyme reactor-nanoflow liquid chromatography-tandem mass spectrometry 95:177 hollow fiber enzyme reactor-nanoflow liquid chromatography-tandem mass spectrometry 95:177 Isotope-coded carbamidomethylation for quantification of N-glycoproteins with online microbore hollow fiber enzyme reactor-nanoflow liquid chromatography-tandem mass spectrometry. 24960276 5 93 gly N-glycopeptides 1467:1481 arg1 N-glycoproteins 1492:1506 49 N-glycoproteins 1489:1506 49 N-glycoproteins 1489:1506 The iCCM quantitation with mHFER-nLC-MS/MS was evaluated with three standard glycoproteins (α-1-acid glycoproteins, fetuin and transferrin) and then applied to serum glycoproteins from liver cancer patients and controls, resulting in successful quantification of 73 N-glycopeptides (from 49 N-glycoproteins), among which 19 N-glycopeptides from 14 N-glycoproteins showed more than a 2.5-fold aberrant change in liver cancer patients' sera compared with the pooled control. 24960276 5 93 gly N-glycopeptides 1467:1481 arg2 N-glycopeptides 1467:1481 73 N-glycopeptides 1464:1481 73 N-glycopeptides (from 49 N-glycoproteins) 1464:1507 The iCCM quantitation with mHFER-nLC-MS/MS was evaluated with three standard glycoproteins (α-1-acid glycoproteins, fetuin and transferrin) and then applied to serum glycoproteins from liver cancer patients and controls, resulting in successful quantification of 73 N-glycopeptides (from 49 N-glycoproteins), among which 19 N-glycopeptides from 14 N-glycoproteins showed more than a 2.5-fold aberrant change in liver cancer patients' sera compared with the pooled control. 24960276 0 94 theme mass 161:164 arg1 spectrometry 166:177 hollow fiber enzyme reactor-nanoflow liquid chromatography-tandem mass spectrometry 95:177 hollow fiber enzyme reactor-nanoflow liquid chromatography-tandem mass spectrometry 95:177 Isotope-coded carbamidomethylation for quantification of N-glycoproteins with online microbore hollow fiber enzyme reactor-nanoflow liquid chromatography-tandem mass spectrometry. 24960276 1 95 theme liquid 435:440 arg1 mHFER-nLC-MS/MS 483:497 mHFER-nLC-MS/MS 483:497 mHFER-nLC-MS/MS 483:497 This paper introduces a simple, inexpensive, and robust quantitative proteomic method for quantifying N-linked glycoproteins based on isotope-coded carbamidomethylation (iCCM) incorporated into an online microbore hollow fiber enzyme reactor and nanoflow liquid chromatography-tandem mass spectrometry (mHFER-nLC-MS/MS). 24960276 1 95 theme liquid 435:440 arg1 spectrometry 469:480 nanoflow liquid chromatography-tandem mass spectrometry 426:480 nanoflow liquid chromatography-tandem mass spectrometry (mHFER-nLC-MS/MS) 426:498 This paper introduces a simple, inexpensive, and robust quantitative proteomic method for quantifying N-linked glycoproteins based on isotope-coded carbamidomethylation (iCCM) incorporated into an online microbore hollow fiber enzyme reactor and nanoflow liquid chromatography-tandem mass spectrometry (mHFER-nLC-MS/MS). 24960276 1 96 gly glycoproteins 291:303 arg1 glycoproteins 291:303 N-linked glycoproteins 282:303 N-linked glycoproteins based on isotope-coded carbamidomethylation (iCCM) incorporated into an online microbore hollow fiber enzyme reactor and nanoflow liquid chromatography-tandem mass spectrometry (mHFER-nLC-MS/MS) 282:498 This paper introduces a simple, inexpensive, and robust quantitative proteomic method for quantifying N-linked glycoproteins based on isotope-coded carbamidomethylation (iCCM) incorporated into an online microbore hollow fiber enzyme reactor and nanoflow liquid chromatography-tandem mass spectrometry (mHFER-nLC-MS/MS). 24960276 5 97 from controls 1412:1419 arg1 glycoproteins 1367:1379 serum glycoproteins 1361:1379 serum glycoproteins 1361:1379 The iCCM quantitation with mHFER-nLC-MS/MS was evaluated with three standard glycoproteins (α-1-acid glycoproteins, fetuin and transferrin) and then applied to serum glycoproteins from liver cancer patients and controls, resulting in successful quantification of 73 N-glycopeptides (from 49 N-glycoproteins), among which 19 N-glycopeptides from 14 N-glycoproteins showed more than a 2.5-fold aberrant change in liver cancer patients' sera compared with the pooled control. 24960276 4 98 theme method 978:983 arg1 evaluation 955:964 Initial evaluation 947:964 Initial evaluation of the iCCM method varying the mixing ratio of CM-/iCCM-labeled bovine serum albumin (BSA) standards 947:1065 Initial evaluation of the iCCM method varying the mixing ratio of CM-/iCCM-labeled bovine serum albumin (BSA) standards yielded successful quantification of 18 peptides with less than 2% variation in the calculated ratio of light/heavy-labeled peptides. 24960276 6 99 gly glycoproteins 1863:1875 arg1 glycoproteins 1863:1875 targeted glycoproteins 1854:1875 targeted glycoproteins 1854:1875 Although iCCM quantitation with mHFER-nLC-MS/MS applies only to glycopeptides with Cys residue, the method can offer several advantages over other labeling methods when applied to targeted glycoproteins: The iCCM method does not require an additional labeling reaction under special conditions nor complicated procedures to purify labeled products using additional columns. 24960276 1 100 theme N-linked 282:289 arg1 glycoproteins 291:303 N-linked glycoproteins 282:303 N-linked glycoproteins based on isotope-coded carbamidomethylation (iCCM) incorporated into an online microbore hollow fiber enzyme reactor and nanoflow liquid chromatography-tandem mass spectrometry (mHFER-nLC-MS/MS) 282:498 This paper introduces a simple, inexpensive, and robust quantitative proteomic method for quantifying N-linked glycoproteins based on isotope-coded carbamidomethylation (iCCM) incorporated into an online microbore hollow fiber enzyme reactor and nanoflow liquid chromatography-tandem mass spectrometry (mHFER-nLC-MS/MS). 24960276 5 101 theme liver 1386:1390 arg1 patients 1399:1406 liver cancer patients 1386:1406 liver cancer patients 1386:1406 The iCCM quantitation with mHFER-nLC-MS/MS was evaluated with three standard glycoproteins (α-1-acid glycoproteins, fetuin and transferrin) and then applied to serum glycoproteins from liver cancer patients and controls, resulting in successful quantification of 73 N-glycopeptides (from 49 N-glycoproteins), among which 19 N-glycopeptides from 14 N-glycoproteins showed more than a 2.5-fold aberrant change in liver cancer patients' sera compared with the pooled control. 24960276 5 102 gly N-glycopeptides 1525:1539 arg2 N-glycopeptides 1525:1539 19 N-glycopeptides 1522:1539 19 N-glycopeptides from 14 N-glycoproteins 1522:1563 The iCCM quantitation with mHFER-nLC-MS/MS was evaluated with three standard glycoproteins (α-1-acid glycoproteins, fetuin and transferrin) and then applied to serum glycoproteins from liver cancer patients and controls, resulting in successful quantification of 73 N-glycopeptides (from 49 N-glycoproteins), among which 19 N-glycopeptides from 14 N-glycoproteins showed more than a 2.5-fold aberrant change in liver cancer patients' sera compared with the pooled control. 24960276 5 102 gly N-glycopeptides 1525:1539 arg1 N-glycoproteins 1549:1563 14 N-glycoproteins 1546:1563 14 N-glycoproteins 1546:1563 The iCCM quantitation with mHFER-nLC-MS/MS was evaluated with three standard glycoproteins (α-1-acid glycoproteins, fetuin and transferrin) and then applied to serum glycoproteins from liver cancer patients and controls, resulting in successful quantification of 73 N-glycopeptides (from 49 N-glycoproteins), among which 19 N-glycopeptides from 14 N-glycoproteins showed more than a 2.5-fold aberrant change in liver cancer patients' sera compared with the pooled control. 24960276 6 103 with quantitation 1688:1699 arg1 mHFER-nLC-MS/MS 1706:1720 mHFER-nLC-MS/MS 1706:1720 mHFER-nLC-MS/MS 1706:1720 Although iCCM quantitation with mHFER-nLC-MS/MS applies only to glycopeptides with Cys residue, the method can offer several advantages over other labeling methods when applied to targeted glycoproteins: The iCCM method does not require an additional labeling reaction under special conditions nor complicated procedures to purify labeled products using additional columns. 24960276 1 104 theme mass 464:467 arg1 mHFER-nLC-MS/MS 483:497 mHFER-nLC-MS/MS 483:497 mHFER-nLC-MS/MS 483:497 This paper introduces a simple, inexpensive, and robust quantitative proteomic method for quantifying N-linked glycoproteins based on isotope-coded carbamidomethylation (iCCM) incorporated into an online microbore hollow fiber enzyme reactor and nanoflow liquid chromatography-tandem mass spectrometry (mHFER-nLC-MS/MS). 24960276 1 104 theme mass 464:467 arg1 spectrometry 469:480 nanoflow liquid chromatography-tandem mass spectrometry 426:480 nanoflow liquid chromatography-tandem mass spectrometry (mHFER-nLC-MS/MS) 426:498 This paper introduces a simple, inexpensive, and robust quantitative proteomic method for quantifying N-linked glycoproteins based on isotope-coded carbamidomethylation (iCCM) incorporated into an online microbore hollow fiber enzyme reactor and nanoflow liquid chromatography-tandem mass spectrometry (mHFER-nLC-MS/MS). 24960276 2 105 dep CM 550:551 arg1 protection 564:573 a routine protection 554:573 CM; a routine protection of thiol groups before proteolysis 550:608 The iCCM quantitation uses carbamidomethylation (CM; a routine protection of thiol groups before proteolysis) of the Cys residue of proteins with iodoacetamide (IAA) or its isotope (IAA-(13)C2,D2: 4 Da difference). 24960276 7 106 from retrieval 2202:2210 arg1 vials 2192:2196 separate vials 2183:2196 separate vials 2183:2196 Isotope labeling at the protein level can minimize potential uncertainty originating from unequal efficiencies in protein digestion in separate vials and retrieval of each labeled peptide when labeling takes place at the peptide level. 24960276 5 107 from patients 1399:1406 arg1 glycoproteins 1367:1379 serum glycoproteins 1361:1379 serum glycoproteins 1361:1379 The iCCM quantitation with mHFER-nLC-MS/MS was evaluated with three standard glycoproteins (α-1-acid glycoproteins, fetuin and transferrin) and then applied to serum glycoproteins from liver cancer patients and controls, resulting in successful quantification of 73 N-glycopeptides (from 49 N-glycoproteins), among which 19 N-glycopeptides from 14 N-glycoproteins showed more than a 2.5-fold aberrant change in liver cancer patients' sera compared with the pooled control. 24960276 5 108 theme iCCM 1205:1208 arg1 quantitation 1210:1221 The iCCM quantitation 1201:1221 The iCCM quantitation with mHFER-nLC-MS/MS 1201:1242 The iCCM quantitation with mHFER-nLC-MS/MS was evaluated with three standard glycoproteins (α-1-acid glycoproteins, fetuin and transferrin) and then applied to serum glycoproteins from liver cancer patients and controls, resulting in successful quantification of 73 N-glycopeptides (from 49 N-glycoproteins), among which 19 N-glycopeptides from 14 N-glycoproteins showed more than a 2.5-fold aberrant change in liver cancer patients' sera compared with the pooled control. 24960276 6 109 theme iCCM 1683:1686 arg1 quantitation 1688:1699 iCCM quantitation 1683:1699 iCCM quantitation with mHFER-nLC-MS/MS 1683:1720 Although iCCM quantitation with mHFER-nLC-MS/MS applies only to glycopeptides with Cys residue, the method can offer several advantages over other labeling methods when applied to targeted glycoproteins: The iCCM method does not require an additional labeling reaction under special conditions nor complicated procedures to purify labeled products using additional columns. 24960276 6 110 theme targeted 1854:1861 arg1 glycoproteins 1863:1875 targeted glycoproteins 1854:1875 targeted glycoproteins 1854:1875 Although iCCM quantitation with mHFER-nLC-MS/MS applies only to glycopeptides with Cys residue, the method can offer several advantages over other labeling methods when applied to targeted glycoproteins: The iCCM method does not require an additional labeling reaction under special conditions nor complicated procedures to purify labeled products using additional columns. 24960276 5 111 theme aberrant 1593:1600 arg1 change 1602:1607 a 2.5-fold aberrant change 1582:1607 a 2.5-fold aberrant change in liver cancer patients' sera 1582:1638 The iCCM quantitation with mHFER-nLC-MS/MS was evaluated with three standard glycoproteins (α-1-acid glycoproteins, fetuin and transferrin) and then applied to serum glycoproteins from liver cancer patients and controls, resulting in successful quantification of 73 N-glycopeptides (from 49 N-glycoproteins), among which 19 N-glycopeptides from 14 N-glycoproteins showed more than a 2.5-fold aberrant change in liver cancer patients' sera compared with the pooled control. 24960276 2 112 theme iCCM 505:508 arg1 quantitation 510:521 The iCCM quantitation 501:521 The iCCM quantitation 501:521 The iCCM quantitation uses carbamidomethylation (CM; a routine protection of thiol groups before proteolysis) of the Cys residue of proteins with iodoacetamide (IAA) or its isotope (IAA-(13)C2,D2: 4 Da difference). 24960276 0 113 theme N-glycoproteins 57:71 arg1 quantification 39:52 quantification 39:52 quantification of N-glycoproteins 39:71 Isotope-coded carbamidomethylation for quantification of N-glycoproteins with online microbore hollow fiber enzyme reactor-nanoflow liquid chromatography-tandem mass spectrometry. 24960276 7 114 theme labeled 2220:2226 arg1 peptide 2228:2234 each labeled peptide 2215:2234 each labeled peptide 2215:2234 Isotope labeling at the protein level can minimize potential uncertainty originating from unequal efficiencies in protein digestion in separate vials and retrieval of each labeled peptide when labeling takes place at the peptide level. 24960276 4 115 theme CM-/iCCM-labeled 1013:1028 arg1 standards 1057:1065 CM-/iCCM-labeled bovine serum albumin (BSA) standards 1013:1065 CM-/iCCM-labeled bovine serum albumin (BSA) standards 1013:1065 Initial evaluation of the iCCM method varying the mixing ratio of CM-/iCCM-labeled bovine serum albumin (BSA) standards yielded successful quantification of 18 peptides with less than 2% variation in the calculated ratio of light/heavy-labeled peptides. 24960276 1 116 theme online 377:382 arg1 reactor 414:420 an online microbore hollow fiber enzyme reactor 374:420 an online microbore hollow fiber enzyme reactor 374:420 This paper introduces a simple, inexpensive, and robust quantitative proteomic method for quantifying N-linked glycoproteins based on isotope-coded carbamidomethylation (iCCM) incorporated into an online microbore hollow fiber enzyme reactor and nanoflow liquid chromatography-tandem mass spectrometry (mHFER-nLC-MS/MS). 24960276 8 117 theme reasonable 2365:2374 arg1 cost 2376:2379 a reasonable cost 2363:2379 a reasonable cost 2363:2379 In addition, the labeling reagents for the iCCM method are readily obtained at a reasonable cost, which can make protein quantification easily accessible. 24960276 4 118 theme serum 1037:1041 arg1 BSA 1052:1054 BSA 1052:1054 BSA 1052:1054 Initial evaluation of the iCCM method varying the mixing ratio of CM-/iCCM-labeled bovine serum albumin (BSA) standards yielded successful quantification of 18 peptides with less than 2% variation in the calculated ratio of light/heavy-labeled peptides. 24960276 4 118 theme serum 1037:1041 arg1 albumin 1043:1049 bovine serum albumin 1030:1049 CM-/iCCM-labeled bovine serum albumin (BSA) standards 1013:1065 Initial evaluation of the iCCM method varying the mixing ratio of CM-/iCCM-labeled bovine serum albumin (BSA) standards yielded successful quantification of 18 peptides with less than 2% variation in the calculated ratio of light/heavy-labeled peptides. 24960276 5 119 gly glycoproteins 1302:1314 arg1 transferrin 1328:1338 transferrin 1328:1338 transferrin 1328:1338 The iCCM quantitation with mHFER-nLC-MS/MS was evaluated with three standard glycoproteins (α-1-acid glycoproteins, fetuin and transferrin) and then applied to serum glycoproteins from liver cancer patients and controls, resulting in successful quantification of 73 N-glycopeptides (from 49 N-glycoproteins), among which 19 N-glycopeptides from 14 N-glycoproteins showed more than a 2.5-fold aberrant change in liver cancer patients' sera compared with the pooled control. 24960276 5 119 gly glycoproteins 1302:1314 arg1 fetuin 1317:1322 fetuin 1317:1322 fetuin 1317:1322 The iCCM quantitation with mHFER-nLC-MS/MS was evaluated with three standard glycoproteins (α-1-acid glycoproteins, fetuin and transferrin) and then applied to serum glycoproteins from liver cancer patients and controls, resulting in successful quantification of 73 N-glycopeptides (from 49 N-glycoproteins), among which 19 N-glycopeptides from 14 N-glycoproteins showed more than a 2.5-fold aberrant change in liver cancer patients' sera compared with the pooled control. 24960276 5 119 gly glycoproteins 1302:1314 arg1 glycoproteins 1302:1314 α-1-acid glycoproteins 1293:1314 α-1-acid glycoproteins 1293:1314 The iCCM quantitation with mHFER-nLC-MS/MS was evaluated with three standard glycoproteins (α-1-acid glycoproteins, fetuin and transferrin) and then applied to serum glycoproteins from liver cancer patients and controls, resulting in successful quantification of 73 N-glycopeptides (from 49 N-glycoproteins), among which 19 N-glycopeptides from 14 N-glycoproteins showed more than a 2.5-fold aberrant change in liver cancer patients' sera compared with the pooled control. 24960276 5 120 theme successful 1435:1444 arg1 quantification 1446:1459 successful quantification 1435:1459 successful quantification of 73 N-glycopeptides (from 49 N-glycoproteins) 1435:1507 The iCCM quantitation with mHFER-nLC-MS/MS was evaluated with three standard glycoproteins (α-1-acid glycoproteins, fetuin and transferrin) and then applied to serum glycoproteins from liver cancer patients and controls, resulting in successful quantification of 73 N-glycopeptides (from 49 N-glycoproteins), among which 19 N-glycopeptides from 14 N-glycoproteins showed more than a 2.5-fold aberrant change in liver cancer patients' sera compared with the pooled control. 24960276 1 121 theme hollow 394:399 arg1 reactor 414:420 an online microbore hollow fiber enzyme reactor 374:420 an online microbore hollow fiber enzyme reactor 374:420 This paper introduces a simple, inexpensive, and robust quantitative proteomic method for quantifying N-linked glycoproteins based on isotope-coded carbamidomethylation (iCCM) incorporated into an online microbore hollow fiber enzyme reactor and nanoflow liquid chromatography-tandem mass spectrometry (mHFER-nLC-MS/MS). 24960276 6 122 theme additional 1914:1923 arg1 reaction 1934:1941 an additional labeling reaction 1911:1941 an additional labeling reaction under special conditions nor complicated procedures to purify labeled products using additional columns 1911:2045 Although iCCM quantitation with mHFER-nLC-MS/MS applies only to glycopeptides with Cys residue, the method can offer several advantages over other labeling methods when applied to targeted glycoproteins: The iCCM method does not require an additional labeling reaction under special conditions nor complicated procedures to purify labeled products using additional columns. 24960276 2 123 with proteins 633:640 arg1 iodoacetamide 647:659 iodoacetamide 647:659 iodoacetamide (IAA) 647:665 The iCCM quantitation uses carbamidomethylation (CM; a routine protection of thiol groups before proteolysis) of the Cys residue of proteins with iodoacetamide (IAA) or its isotope (IAA-(13)C2,D2: 4 Da difference). 24960276 2 123 with proteins 633:640 arg1 isotope 674:680 its isotope 670:680 its isotope (IAA-(13)C2,D2: 4 Da difference) 670:713 The iCCM quantitation uses carbamidomethylation (CM; a routine protection of thiol groups before proteolysis) of the Cys residue of proteins with iodoacetamide (IAA) or its isotope (IAA-(13)C2,D2: 4 Da difference). 24960276 2 123 with proteins 633:640 arg1 IAA 662:664 IAA 662:664 IAA 662:664 The iCCM quantitation uses carbamidomethylation (CM; a routine protection of thiol groups before proteolysis) of the Cys residue of proteins with iodoacetamide (IAA) or its isotope (IAA-(13)C2,D2: 4 Da difference). 24960276 5 124 theme standard 1269:1276 arg1 glycoproteins 1278:1290 three standard glycoproteins 1263:1290 three standard glycoproteins (α-1-acid glycoproteins, fetuin and transferrin) 1263:1339 The iCCM quantitation with mHFER-nLC-MS/MS was evaluated with three standard glycoproteins (α-1-acid glycoproteins, fetuin and transferrin) and then applied to serum glycoproteins from liver cancer patients and controls, resulting in successful quantification of 73 N-glycopeptides (from 49 N-glycoproteins), among which 19 N-glycopeptides from 14 N-glycoproteins showed more than a 2.5-fold aberrant change in liver cancer patients' sera compared with the pooled control. 24960276 7 125 theme peptide 2228:2234 arg1 retrieval 2202:2210 retrieval 2202:2210 retrieval of each labeled peptide 2202:2234 Isotope labeling at the protein level can minimize potential uncertainty originating from unequal efficiencies in protein digestion in separate vials and retrieval of each labeled peptide when labeling takes place at the peptide level. 24960276 7 125 theme peptide 2228:2234 arg1 digestion 2170:2178 protein digestion 2162:2178 protein digestion in separate vials 2162:2196 Isotope labeling at the protein level can minimize potential uncertainty originating from unequal efficiencies in protein digestion in separate vials and retrieval of each labeled peptide when labeling takes place at the peptide level. 24960276 5 126 from N-glycoproteins 1492:1506 arg1 N-glycopeptides 1467:1481 73 N-glycopeptides 1464:1481 73 N-glycopeptides (from 49 N-glycoproteins) 1464:1507 The iCCM quantitation with mHFER-nLC-MS/MS was evaluated with three standard glycoproteins (α-1-acid glycoproteins, fetuin and transferrin) and then applied to serum glycoproteins from liver cancer patients and controls, resulting in successful quantification of 73 N-glycopeptides (from 49 N-glycoproteins), among which 19 N-glycopeptides from 14 N-glycoproteins showed more than a 2.5-fold aberrant change in liver cancer patients' sera compared with the pooled control. 24960276 5 126 from N-glycoproteins 1492:1506 arg1 quantification 1446:1459 successful quantification 1435:1459 successful quantification of 73 N-glycopeptides (from 49 N-glycoproteins) 1435:1507 The iCCM quantitation with mHFER-nLC-MS/MS was evaluated with three standard glycoproteins (α-1-acid glycoproteins, fetuin and transferrin) and then applied to serum glycoproteins from liver cancer patients and controls, resulting in successful quantification of 73 N-glycopeptides (from 49 N-glycoproteins), among which 19 N-glycopeptides from 14 N-glycoproteins showed more than a 2.5-fold aberrant change in liver cancer patients' sera compared with the pooled control. 24960276 7 127 theme Isotope 2048:2054 arg1 labeling 2056:2063 Isotope labeling 2048:2063 Isotope labeling at the protein level 2048:2084 Isotope labeling at the protein level can minimize potential uncertainty originating from unequal efficiencies in protein digestion in separate vials and retrieval of each labeled peptide when labeling takes place at the peptide level. 24960276 3 128 theme CM-/iCCM-labeled 716:731 arg1 samples 742:748 CM-/iCCM-labeled proteome samples 716:748 CM-/iCCM-labeled proteome samples 716:748 CM-/iCCM-labeled proteome samples are mixed for proteolysis; then, online enrichment of N-glycopeptides using lectin affinity is carried out in an mHFER before nLC-MS/MS for quantification using multiple reaction monitoring (MRM). 24630720 4 0 theme protein 498:504 arg1 homeostasis 506:516 ER protein homeostasis 495:516 ER protein homeostasis 495:516 Here, we report that increased synthesis of N-glycan precursors in the hexosamine pathway improves ER protein homeostasis and extends lifespan in C. elegans. 24630720 7 1 theme hexosamine 917:926 arg1 activation 936:945 hexosamine pathway activation 917:945 hexosamine pathway activation 917:945 Evidently, hexosamine pathway activation or N-acetylglucosamine supplementation induces distinct protein quality control mechanisms, which may allow therapeutic intervention against age-related and proteotoxic diseases. 24630720 7 2 theme quality 1011:1017 arg1 mechanisms 1027:1036 distinct protein quality control mechanisms 994:1036 distinct protein quality control mechanisms 994:1036 Evidently, hexosamine pathway activation or N-acetylglucosamine supplementation induces distinct protein quality control mechanisms, which may allow therapeutic intervention against age-related and proteotoxic diseases. 24630720 2 3 dep protein 230:236 arg1 synthesis 238:246 synthesis 238:246 synthesis 238:246 The endoplasmic reticulum (ER) is the site of protein synthesis and maturation for secreted and membrane proteins. 24630720 7 4 theme pathway 928:934 arg1 activation 936:945 hexosamine pathway activation 917:945 hexosamine pathway activation 917:945 Evidently, hexosamine pathway activation or N-acetylglucosamine supplementation induces distinct protein quality control mechanisms, which may allow therapeutic intervention against age-related and proteotoxic diseases. 24630720 6 5 theme protein 848:854 arg1 degradation 856:866 enhanced ER-associated protein degradation 825:866 enhanced ER-associated protein degradation 825:866 Our data suggest that reduced aggregation of metastable proteins and lifespan extension depend on enhanced ER-associated protein degradation, proteasomal activity, and autophagy. 24630720 4 6 theme hexosamine 467:476 arg1 pathway 478:484 the hexosamine pathway 463:484 the hexosamine pathway 463:484 Here, we report that increased synthesis of N-glycan precursors in the hexosamine pathway improves ER protein homeostasis and extends lifespan in C. elegans. 24630720 6 7 theme metastable 772:781 arg1 proteins 783:790 metastable proteins 772:790 metastable proteins 772:790 Our data suggest that reduced aggregation of metastable proteins and lifespan extension depend on enhanced ER-associated protein degradation, proteasomal activity, and autophagy. 24630720 7 8 theme proteotoxic 1104:1114 arg1 diseases 1116:1123 age-related and proteotoxic diseases 1088:1123 diseases 1116:1123 Evidently, hexosamine pathway activation or N-acetylglucosamine supplementation induces distinct protein quality control mechanisms, which may allow therapeutic intervention against age-related and proteotoxic diseases. 24630720 1 9 theme age-related 162:172 arg1 diseases 174:181 age-related diseases 162:181 age-related diseases 162:181 Aging entails a progressive decline in protein homeostasis, which often leads to age-related diseases. 24630720 3 10 theme covalent 339:346 arg1 attachment 348:357 covalent attachment 339:357 covalent attachment of N-linked glycan oligosaccharides 339:393 Correct folding of ER proteins requires covalent attachment of N-linked glycan oligosaccharides. 24630720 4 11 theme ER 495:496 arg1 homeostasis 506:516 ER protein homeostasis 495:516 ER protein homeostasis 495:516 Here, we report that increased synthesis of N-glycan precursors in the hexosamine pathway improves ER protein homeostasis and extends lifespan in C. elegans. 24630720 5 12 theme N-glycan 570:577 arg1 N-acetylglucosamine 589:607 the N-glycan precursor N-acetylglucosamine 566:607 the N-glycan precursor N-acetylglucosamine 566:607 Addition of the N-glycan precursor N-acetylglucosamine to the growth medium slows aging in wild-type animals and alleviates pathology of distinct neurotoxic disease models. 24630720 2 13 theme maturation 252:261 arg1 reticulum 200:208 The endoplasmic reticulum 184:208 The endoplasmic reticulum (ER) 184:213 The endoplasmic reticulum (ER) is the site of protein synthesis and maturation for secreted and membrane proteins. 24630720 2 13 theme maturation 252:261 arg1 maturation 252:261 maturation 252:261 maturation 252:261 The endoplasmic reticulum (ER) is the site of protein synthesis and maturation for secreted and membrane proteins. 24630720 2 13 theme maturation 252:261 arg1 site 222:225 the site 218:225 the site of protein synthesis and maturation for secreted and membrane proteins 218:296 The endoplasmic reticulum (ER) is the site of protein synthesis and maturation for secreted and membrane proteins. 24630720 2 13 theme maturation 252:261 arg1 protein 230:236 protein synthesis and maturation 230:261 protein 230:236 The endoplasmic reticulum (ER) is the site of protein synthesis and maturation for secreted and membrane proteins. 24630720 0 14 theme pathway 11:17 arg1 metabolites 19:29 Hexosamine pathway metabolites 0:29 Hexosamine pathway metabolites 0:29 Hexosamine pathway metabolites enhance protein quality control and prolong life. 24630720 5 15 theme wild-type 645:653 arg1 animals 655:661 wild-type animals 645:661 wild-type animals 645:661 Addition of the N-glycan precursor N-acetylglucosamine to the growth medium slows aging in wild-type animals and alleviates pathology of distinct neurotoxic disease models. 24630720 5 16 theme precursor 579:587 arg1 N-acetylglucosamine 589:607 the N-glycan precursor N-acetylglucosamine 566:607 the N-glycan precursor N-acetylglucosamine 566:607 Addition of the N-glycan precursor N-acetylglucosamine to the growth medium slows aging in wild-type animals and alleviates pathology of distinct neurotoxic disease models. 24630720 4 17 from synthesis 427:435 arg1 pathway 478:484 the hexosamine pathway 463:484 the hexosamine pathway 463:484 Here, we report that increased synthesis of N-glycan precursors in the hexosamine pathway improves ER protein homeostasis and extends lifespan in C. elegans. 24630720 0 18 theme Hexosamine 0:9 arg1 metabolites 19:29 Hexosamine pathway metabolites 0:29 Hexosamine pathway metabolites 0:29 Hexosamine pathway metabolites enhance protein quality control and prolong life. 24630720 6 19 theme proteasomal 869:879 arg1 activity 881:888 proteasomal activity 869:888 proteasomal activity 869:888 Our data suggest that reduced aggregation of metastable proteins and lifespan extension depend on enhanced ER-associated protein degradation, proteasomal activity, and autophagy. 24630720 5 20 theme N-acetylglucosamine 589:607 arg1 Addition 554:561 Addition 554:561 Addition of the N-glycan precursor N-acetylglucosamine to the growth medium 554:628 Addition of the N-glycan precursor N-acetylglucosamine to the growth medium slows aging in wild-type animals and alleviates pathology of distinct neurotoxic disease models. 24630720 3 21 theme N-linked 362:369 arg1 oligosaccharides 378:393 N-linked glycan oligosaccharides 362:393 N-linked glycan oligosaccharides 362:393 Correct folding of ER proteins requires covalent attachment of N-linked glycan oligosaccharides. 24630720 7 22 theme protein 1003:1009 arg1 mechanisms 1027:1036 distinct protein quality control mechanisms 994:1036 distinct protein quality control mechanisms 994:1036 Evidently, hexosamine pathway activation or N-acetylglucosamine supplementation induces distinct protein quality control mechanisms, which may allow therapeutic intervention against age-related and proteotoxic diseases. 24630720 6 23 theme ER-associated 834:846 arg1 degradation 856:866 enhanced ER-associated protein degradation 825:866 enhanced ER-associated protein degradation 825:866 Our data suggest that reduced aggregation of metastable proteins and lifespan extension depend on enhanced ER-associated protein degradation, proteasomal activity, and autophagy. 24630720 1 24 theme progressive 97:107 arg1 decline 109:115 a progressive decline 95:115 a progressive decline 95:115 Aging entails a progressive decline in protein homeostasis, which often leads to age-related diseases. 24630720 3 25 theme glycan 371:376 arg1 oligosaccharides 378:393 N-linked glycan oligosaccharides 362:393 N-linked glycan oligosaccharides 362:393 Correct folding of ER proteins requires covalent attachment of N-linked glycan oligosaccharides. 24630720 5 26 from aging 636:640 arg1 animals 655:661 wild-type animals 645:661 wild-type animals 645:661 Addition of the N-glycan precursor N-acetylglucosamine to the growth medium slows aging in wild-type animals and alleviates pathology of distinct neurotoxic disease models. 24630720 7 27 theme therapeutic 1055:1065 arg1 intervention 1067:1078 therapeutic intervention 1055:1078 therapeutic intervention against age-related and proteotoxic diseases 1055:1123 Evidently, hexosamine pathway activation or N-acetylglucosamine supplementation induces distinct protein quality control mechanisms, which may allow therapeutic intervention against age-related and proteotoxic diseases. 24630720 4 28 theme precursors 449:458 arg1 synthesis 427:435 increased synthesis 417:435 increased synthesis of N-glycan precursors in the hexosamine pathway 417:484 Here, we report that increased synthesis of N-glycan precursors in the hexosamine pathway improves ER protein homeostasis and extends lifespan in C. elegans. 24630720 2 29 theme membrane 280:287 arg1 proteins 289:296 membrane proteins 280:296 membrane proteins 280:296 The endoplasmic reticulum (ER) is the site of protein synthesis and maturation for secreted and membrane proteins. 24630720 0 30 theme quality 47:53 arg1 control 55:61 protein quality control 39:61 protein quality control 39:61 Hexosamine pathway metabolites enhance protein quality control and prolong life. 24630720 4 31 theme N-glycan 440:447 arg1 precursors 449:458 N-glycan precursors 440:458 N-glycan precursors 440:458 Here, we report that increased synthesis of N-glycan precursors in the hexosamine pathway improves ER protein homeostasis and extends lifespan in C. elegans. 24630720 0 32 theme protein 39:45 arg1 control 55:61 protein quality control 39:61 protein quality control 39:61 Hexosamine pathway metabolites enhance protein quality control and prolong life. 24630720 6 33 theme lifespan 796:803 arg1 extension 805:813 lifespan extension 796:813 lifespan extension 796:813 Our data suggest that reduced aggregation of metastable proteins and lifespan extension depend on enhanced ER-associated protein degradation, proteasomal activity, and autophagy. 24630720 5 34 theme distinct 691:698 arg1 models 719:724 distinct neurotoxic disease models 691:724 distinct neurotoxic disease models 691:724 Addition of the N-glycan precursor N-acetylglucosamine to the growth medium slows aging in wild-type animals and alleviates pathology of distinct neurotoxic disease models. 24630720 4 35 from lifespan 530:537 arg1 elegans 545:551 C. elegans 542:551 C. elegans 542:551 Here, we report that increased synthesis of N-glycan precursors in the hexosamine pathway improves ER protein homeostasis and extends lifespan in C. elegans. 24630720 3 36 theme Correct 299:305 arg1 folding 307:313 Correct folding 299:313 Correct folding of ER proteins 299:328 Correct folding of ER proteins requires covalent attachment of N-linked glycan oligosaccharides. 24630720 4 37 theme increased 417:425 arg1 synthesis 427:435 increased synthesis 417:435 increased synthesis of N-glycan precursors in the hexosamine pathway 417:484 Here, we report that increased synthesis of N-glycan precursors in the hexosamine pathway improves ER protein homeostasis and extends lifespan in C. elegans. 24630720 7 38 theme control 1019:1025 arg1 mechanisms 1027:1036 distinct protein quality control mechanisms 994:1036 distinct protein quality control mechanisms 994:1036 Evidently, hexosamine pathway activation or N-acetylglucosamine supplementation induces distinct protein quality control mechanisms, which may allow therapeutic intervention against age-related and proteotoxic diseases. 24630720 6 39 theme proteins 783:790 arg1 aggregation 757:767 reduced aggregation 749:767 reduced aggregation of metastable proteins 749:790 Our data suggest that reduced aggregation of metastable proteins and lifespan extension depend on enhanced ER-associated protein degradation, proteasomal activity, and autophagy. 24630720 6 39 theme proteins 783:790 arg1 extension 805:813 lifespan extension 796:813 lifespan extension 796:813 Our data suggest that reduced aggregation of metastable proteins and lifespan extension depend on enhanced ER-associated protein degradation, proteasomal activity, and autophagy. 24630720 1 40 theme protein 120:126 arg1 homeostasis 128:138 protein homeostasis 120:138 protein homeostasis 120:138 Aging entails a progressive decline in protein homeostasis, which often leads to age-related diseases. 24630720 4 41 theme C. 542:543 arg1 elegans 545:551 C. elegans 542:551 C. elegans 542:551 Here, we report that increased synthesis of N-glycan precursors in the hexosamine pathway improves ER protein homeostasis and extends lifespan in C. elegans. 24630720 5 42 theme disease 711:717 arg1 models 719:724 distinct neurotoxic disease models 691:724 distinct neurotoxic disease models 691:724 Addition of the N-glycan precursor N-acetylglucosamine to the growth medium slows aging in wild-type animals and alleviates pathology of distinct neurotoxic disease models. 24630720 6 43 theme enhanced 825:832 arg1 degradation 856:866 enhanced ER-associated protein degradation 825:866 enhanced ER-associated protein degradation 825:866 Our data suggest that reduced aggregation of metastable proteins and lifespan extension depend on enhanced ER-associated protein degradation, proteasomal activity, and autophagy. 24630720 3 44 link N-linked 362:369 arg1 oligosaccharides 378:393 N-linked glycan oligosaccharides 362:393 N-linked glycan oligosaccharides 362:393 Correct folding of ER proteins requires covalent attachment of N-linked glycan oligosaccharides. 24630720 5 45 theme growth 616:621 arg1 medium 623:628 the growth medium 612:628 the growth medium 612:628 Addition of the N-glycan precursor N-acetylglucosamine to the growth medium slows aging in wild-type animals and alleviates pathology of distinct neurotoxic disease models. 24630720 1 46 from decline 109:115 arg1 homeostasis 128:138 protein homeostasis 120:138 protein homeostasis 120:138 Aging entails a progressive decline in protein homeostasis, which often leads to age-related diseases. 24630720 5 47 theme models 719:724 arg1 pathology 678:686 pathology 678:686 pathology of distinct neurotoxic disease models 678:724 Addition of the N-glycan precursor N-acetylglucosamine to the growth medium slows aging in wild-type animals and alleviates pathology of distinct neurotoxic disease models. 24630720 7 48 theme N-acetylglucosamine 950:968 arg1 supplementation 970:984 N-acetylglucosamine supplementation 950:984 N-acetylglucosamine supplementation 950:984 Evidently, hexosamine pathway activation or N-acetylglucosamine supplementation induces distinct protein quality control mechanisms, which may allow therapeutic intervention against age-related and proteotoxic diseases. 24630720 3 49 theme ER 318:319 arg1 proteins 321:328 ER proteins 318:328 ER proteins 318:328 Correct folding of ER proteins requires covalent attachment of N-linked glycan oligosaccharides. 24630720 2 50 theme endoplasmic 188:198 arg1 reticulum 200:208 The endoplasmic reticulum 184:208 The endoplasmic reticulum (ER) 184:213 The endoplasmic reticulum (ER) is the site of protein synthesis and maturation for secreted and membrane proteins. 24630720 2 50 theme endoplasmic 188:198 arg1 maturation 252:261 maturation 252:261 maturation 252:261 The endoplasmic reticulum (ER) is the site of protein synthesis and maturation for secreted and membrane proteins. 24630720 2 50 theme endoplasmic 188:198 arg1 site 222:225 the site 218:225 the site of protein synthesis and maturation for secreted and membrane proteins 218:296 The endoplasmic reticulum (ER) is the site of protein synthesis and maturation for secreted and membrane proteins. 24630720 2 50 theme endoplasmic 188:198 arg1 protein 230:236 protein synthesis and maturation 230:261 protein 230:236 The endoplasmic reticulum (ER) is the site of protein synthesis and maturation for secreted and membrane proteins. 24630720 2 50 theme endoplasmic 188:198 arg1 ER 211:212 ER 211:212 ER 211:212 The endoplasmic reticulum (ER) is the site of protein synthesis and maturation for secreted and membrane proteins. 24630720 2 51 theme protein 230:236 arg1 reticulum 200:208 The endoplasmic reticulum 184:208 The endoplasmic reticulum (ER) 184:213 The endoplasmic reticulum (ER) is the site of protein synthesis and maturation for secreted and membrane proteins. 24630720 2 51 theme protein 230:236 arg1 maturation 252:261 maturation 252:261 maturation 252:261 The endoplasmic reticulum (ER) is the site of protein synthesis and maturation for secreted and membrane proteins. 24630720 2 51 theme protein 230:236 arg1 site 222:225 the site 218:225 the site of protein synthesis and maturation for secreted and membrane proteins 218:296 The endoplasmic reticulum (ER) is the site of protein synthesis and maturation for secreted and membrane proteins. 24630720 2 51 theme protein 230:236 arg1 protein 230:236 protein synthesis and maturation 230:261 protein 230:236 The endoplasmic reticulum (ER) is the site of protein synthesis and maturation for secreted and membrane proteins. 24630720 7 52 theme age-related 1088:1098 arg1 diseases 1116:1123 age-related and proteotoxic diseases 1088:1123 diseases 1116:1123 Evidently, hexosamine pathway activation or N-acetylglucosamine supplementation induces distinct protein quality control mechanisms, which may allow therapeutic intervention against age-related and proteotoxic diseases. 24630720 7 53 theme distinct 994:1001 arg1 mechanisms 1027:1036 distinct protein quality control mechanisms 994:1036 distinct protein quality control mechanisms 994:1036 Evidently, hexosamine pathway activation or N-acetylglucosamine supplementation induces distinct protein quality control mechanisms, which may allow therapeutic intervention against age-related and proteotoxic diseases. 24630720 3 54 theme proteins 321:328 arg1 folding 307:313 Correct folding 299:313 Correct folding of ER proteins 299:328 Correct folding of ER proteins requires covalent attachment of N-linked glycan oligosaccharides. 24630720 6 55 theme reduced 749:755 arg1 aggregation 757:767 reduced aggregation 749:767 reduced aggregation of metastable proteins 749:790 Our data suggest that reduced aggregation of metastable proteins and lifespan extension depend on enhanced ER-associated protein degradation, proteasomal activity, and autophagy. 24630720 3 56 theme oligosaccharides 378:393 arg1 attachment 348:357 covalent attachment 339:357 covalent attachment of N-linked glycan oligosaccharides 339:393 Correct folding of ER proteins requires covalent attachment of N-linked glycan oligosaccharides. 24630720 5 57 theme neurotoxic 700:709 arg1 models 719:724 distinct neurotoxic disease models 691:724 distinct neurotoxic disease models 691:724 Addition of the N-glycan precursor N-acetylglucosamine to the growth medium slows aging in wild-type animals and alleviates pathology of distinct neurotoxic disease models. 24550399 6 0 theme analyzed 905:912 arg1 tissues 917:923 all analyzed KO tissues 901:923 all analyzed KO tissues 901:923 Increased amounts of Man(8-9)GlcNAc oligosaccharides were recognized in all analyzed KO tissues. 24550399 10 1 theme tubules 1586:1592 arg1 epithelium 1556:1565 the epithelium 1552:1565 the epithelium of proximal kidney tubules 1552:1592 In addition, lectin screening showed the presence of mannose-containing saccharides in the epithelium of proximal kidney tubules, whereas scattered glomeruli appeared collapsed or featured signs of fibrosis along Bowman's capsule. 24550399 3 2 theme partial 493:499 arg1 demannosylation 501:515 the partial demannosylation 489:515 the partial demannosylation occurring in the cytosol 489:540 α-Mannosidase (MAN2C1) is the enzyme responsible for the partial demannosylation occurring in the cytosol. 24550399 1 3 theme endoplasmic 236:246 arg1 process 281:287 the endoplasmic reticulum-associated degradation process 232:287 the endoplasmic reticulum-associated degradation process 232:287 Free Man(7-9)GlcNAc2 is released during the biosynthesis pathway of N-linked glycans or from misfolded glycoproteins during the endoplasmic reticulum-associated degradation process and are reduced to Man5GlcNAc in the cytosol. 24550399 8 4 theme glycogen 1189:1196 arg1 particles 1198:1206 glycogen particles 1189:1206 glycogen particles 1189:1206 Enterocytes of the small intestine accumulate mannose-containing saccharides and glycogen particles in their apical cytoplasm as well as large clear vacuoles in retronuclear position. 24550399 10 5 theme collapsed 1632:1640 arg1 signs 1654:1658 collapsed or featured signs 1632:1658 collapsed or featured signs of fibrosis 1632:1670 In addition, lectin screening showed the presence of mannose-containing saccharides in the epithelium of proximal kidney tubules, whereas scattered glomeruli appeared collapsed or featured signs of fibrosis along Bowman's capsule. 24550399 1 6 theme degradation 269:279 arg1 process 281:287 the endoplasmic reticulum-associated degradation process 232:287 the endoplasmic reticulum-associated degradation process 232:287 Free Man(7-9)GlcNAc2 is released during the biosynthesis pathway of N-linked glycans or from misfolded glycoproteins during the endoplasmic reticulum-associated degradation process and are reduced to Man5GlcNAc in the cytosol. 24550399 4 7 theme GlcNAc 641:646 arg1 oligosaccharides 648:663 Man(8-9)GlcNAc oligosaccharides 633:663 Man(8-9)GlcNAc oligosaccharides 633:663 It has been demonstrated that the inhibition of MAN2C1 expression induces accumulation of Man(8-9)GlcNAc oligosaccharides and apoptosis in vitro. 24550399 1 8 attach released 132:139 arg1 glycoproteins 211:223 misfolded glycoproteins 201:223 misfolded glycoproteins 201:223 Free Man(7-9)GlcNAc2 is released during the biosynthesis pathway of N-linked glycans or from misfolded glycoproteins during the endoplasmic reticulum-associated degradation process and are reduced to Man5GlcNAc in the cytosol. 24550399 1 8 attach released 132:139 arg2 GlcNAc2 121:127 Free Man(7-9)GlcNAc2 108:127 Free Man(7-9)GlcNAc2 108:127 Free Man(7-9)GlcNAc2 is released during the biosynthesis pathway of N-linked glycans or from misfolded glycoproteins during the endoplasmic reticulum-associated degradation process and are reduced to Man5GlcNAc in the cytosol. 24550399 8 9 theme apical 1217:1222 arg1 cytoplasm 1224:1232 their apical cytoplasm 1211:1232 their apical cytoplasm 1211:1232 Enterocytes of the small intestine accumulate mannose-containing saccharides and glycogen particles in their apical cytoplasm as well as large clear vacuoles in retronuclear position. 24550399 6 10 theme GlcNAc 858:863 arg1 oligosaccharides 865:880 Man(8-9)GlcNAc oligosaccharides 850:880 Man(8-9)GlcNAc oligosaccharides 850:880 Increased amounts of Man(8-9)GlcNAc oligosaccharides were recognized in all analyzed KO tissues. 24550399 7 11 theme matter 1093:1098 arg1 tracts 1100:1105 major telencephalic white matter tracts 1067:1105 major telencephalic white matter tracts 1067:1105 Histological analysis of the CNS revealed neuronal and glial degeneration with formation of multiple vacuoles in deep neocortical layers and major telencephalic white matter tracts. 24550399 4 12 theme Man 633:635 arg1 oligosaccharides 648:663 Man(8-9)GlcNAc oligosaccharides 633:663 Man(8-9)GlcNAc oligosaccharides 633:663 It has been demonstrated that the inhibition of MAN2C1 expression induces accumulation of Man(8-9)GlcNAc oligosaccharides and apoptosis in vitro. 24550399 10 13 theme featured 1645:1652 arg1 signs 1654:1658 collapsed or featured signs 1632:1658 collapsed or featured signs of fibrosis 1632:1670 In addition, lectin screening showed the presence of mannose-containing saccharides in the epithelium of proximal kidney tubules, whereas scattered glomeruli appeared collapsed or featured signs of fibrosis along Bowman's capsule. 24550399 11 14 theme Man2c1 1848:1853 arg1 effects 1827:1833 possible toxic effects 1812:1833 possible toxic effects of truncated Man2c1 1812:1853 Except for a moderate enrichment of mannosyl compounds and glycogen, heterozygous mice were normal, arguing against possible toxic effects of truncated Man2c1. 24550399 7 15 theme telencephalic 1073:1085 arg1 matter 1093:1098 telencephalic white matter 1073:1098 major telencephalic white matter tracts 1067:1105 Histological analysis of the CNS revealed neuronal and glial degeneration with formation of multiple vacuoles in deep neocortical layers and major telencephalic white matter tracts. 24550399 1 16 theme N-linked 176:183 arg1 glycans 185:191 N-linked glycans 176:191 N-linked glycans 176:191 Free Man(7-9)GlcNAc2 is released during the biosynthesis pathway of N-linked glycans or from misfolded glycoproteins during the endoplasmic reticulum-associated degradation process and are reduced to Man5GlcNAc in the cytosol. 24550399 5 17 theme Man2c1-deficient 806:821 arg1 mice 823:826 Man2c1-deficient mice 806:826 Man2c1-deficient mice 806:826 We investigated the consequences caused by the lack of cytosolic α-mannosidase activity in vivo by the generation of Man2c1-deficient mice. 24550399 8 18 theme clear 1251:1255 arg1 vacuoles 1257:1264 large clear vacuoles 1245:1264 mannose-containing saccharides and glycogen particles in their apical cytoplasm as well as large clear vacuoles 1154:1264 Enterocytes of the small intestine accumulate mannose-containing saccharides and glycogen particles in their apical cytoplasm as well as large clear vacuoles in retronuclear position. 24550399 7 19 theme neocortical 1044:1054 arg1 layers 1056:1061 deep neocortical layers 1039:1061 deep neocortical layers 1039:1061 Histological analysis of the CNS revealed neuronal and glial degeneration with formation of multiple vacuoles in deep neocortical layers and major telencephalic white matter tracts. 24550399 1 20 theme Man 113:115 arg1 GlcNAc2 121:127 Free Man(7-9)GlcNAc2 108:127 Free Man(7-9)GlcNAc2 108:127 Free Man(7-9)GlcNAc2 is released during the biosynthesis pathway of N-linked glycans or from misfolded glycoproteins during the endoplasmic reticulum-associated degradation process and are reduced to Man5GlcNAc in the cytosol. 24550399 10 21 from presence 1506:1513 arg1 epithelium 1556:1565 the epithelium 1552:1565 the epithelium of proximal kidney tubules 1552:1592 In addition, lectin screening showed the presence of mannose-containing saccharides in the epithelium of proximal kidney tubules, whereas scattered glomeruli appeared collapsed or featured signs of fibrosis along Bowman's capsule. 24550399 7 22 theme glial 981:985 arg1 degeneration 987:998 neuronal and glial degeneration 968:998 neuronal and glial degeneration 968:998 Histological analysis of the CNS revealed neuronal and glial degeneration with formation of multiple vacuoles in deep neocortical layers and major telencephalic white matter tracts. 24550399 5 23 theme cytosolic 744:752 arg1 activity 768:775 cytosolic α-mannosidase activity 744:775 cytosolic α-mannosidase activity 744:775 We investigated the consequences caused by the lack of cytosolic α-mannosidase activity in vivo by the generation of Man2c1-deficient mice. 24550399 5 24 theme mice 823:826 arg1 generation 792:801 the generation 788:801 the generation of Man2c1-deficient mice 788:826 We investigated the consequences caused by the lack of cytosolic α-mannosidase activity in vivo by the generation of Man2c1-deficient mice. 24550399 7 25 theme neuronal 968:975 arg1 degeneration 987:998 neuronal and glial degeneration 968:998 neuronal and glial degeneration 968:998 Histological analysis of the CNS revealed neuronal and glial degeneration with formation of multiple vacuoles in deep neocortical layers and major telencephalic white matter tracts. 24550399 5 26 theme activity 768:775 arg1 lack 736:739 the lack 732:739 the lack of cytosolic α-mannosidase activity 732:775 We investigated the consequences caused by the lack of cytosolic α-mannosidase activity in vivo by the generation of Man2c1-deficient mice. 24550399 7 27 theme CNS 955:957 arg1 analysis 939:946 Histological analysis 926:946 Histological analysis of the CNS 926:957 Histological analysis of the CNS revealed neuronal and glial degeneration with formation of multiple vacuoles in deep neocortical layers and major telencephalic white matter tracts. 24550399 0 28 from Accumulation 0:11 arg1 mice 102:105 cytosolic α-mannosidase (Man2c1)-deficient mice 59:105 cytosolic α-mannosidase (Man2c1)-deficient mice 59:105 Accumulation of free oligosaccharides and tissue damage in cytosolic α-mannosidase (Man2c1)-deficient mice. 24550399 11 29 theme toxic 1821:1825 arg1 effects 1827:1833 possible toxic effects 1812:1833 possible toxic effects of truncated Man2c1 1812:1853 Except for a moderate enrichment of mannosyl compounds and glycogen, heterozygous mice were normal, arguing against possible toxic effects of truncated Man2c1. 24550399 9 30 theme hepatocytes 1335:1345 arg1 groups 1325:1330 groups 1325:1330 groups of hepatocytes with increased content of mannosyl compounds and glycogen 1325:1403 Liver tissue is characterized by groups of hepatocytes with increased content of mannosyl compounds and glycogen, some of them undergoing degeneration by hydropic swelling. 24550399 9 30 theme hepatocytes 1335:1345 arg1 them 1414:1417 them 1414:1417 them 1414:1417 Liver tissue is characterized by groups of hepatocytes with increased content of mannosyl compounds and glycogen, some of them undergoing degeneration by hydropic swelling. 24550399 9 30 theme hepatocytes 1335:1345 arg1 some 1406:1409 some 1406:1409 some 1406:1409 Liver tissue is characterized by groups of hepatocytes with increased content of mannosyl compounds and glycogen, some of them undergoing degeneration by hydropic swelling. 24550399 9 30 theme hepatocytes 1335:1345 arg1 hepatocytes 1335:1345 hepatocytes 1335:1345 hepatocytes with increased content of mannosyl compounds and glycogen 1335:1403 Liver tissue is characterized by groups of hepatocytes with increased content of mannosyl compounds and glycogen, some of them undergoing degeneration by hydropic swelling. 24550399 10 31 attach presence 1506:1513 arg1 epithelium 1556:1565 the epithelium 1552:1565 the epithelium of proximal kidney tubules 1552:1592 In addition, lectin screening showed the presence of mannose-containing saccharides in the epithelium of proximal kidney tubules, whereas scattered glomeruli appeared collapsed or featured signs of fibrosis along Bowman's capsule. 24550399 10 31 attach presence 1506:1513 arg2 saccharides 1537:1547 mannose-containing saccharides 1518:1547 mannose-containing saccharides 1518:1547 In addition, lectin screening showed the presence of mannose-containing saccharides in the epithelium of proximal kidney tubules, whereas scattered glomeruli appeared collapsed or featured signs of fibrosis along Bowman's capsule. 24550399 9 32 theme increased 1352:1360 arg1 content 1362:1368 increased content 1352:1368 increased content of mannosyl compounds 1352:1390 Liver tissue is characterized by groups of hepatocytes with increased content of mannosyl compounds and glycogen, some of them undergoing degeneration by hydropic swelling. 24550399 12 33 theme oligosaccharides 1935:1950 arg1 catabolism 1916:1925 the catabolism 1912:1925 the catabolism of free oligosaccharides 1912:1950 These findings confirm the key role played by Man2c1 in the catabolism of free oligosaccharides. 24550399 7 34 theme Histological 926:937 arg1 analysis 939:946 Histological analysis 926:946 Histological analysis of the CNS 926:957 Histological analysis of the CNS revealed neuronal and glial degeneration with formation of multiple vacuoles in deep neocortical layers and major telencephalic white matter tracts. 24550399 0 35 theme free 16:19 arg1 oligosaccharides 21:36 free oligosaccharides 16:36 free oligosaccharides 16:36 Accumulation of free oligosaccharides and tissue damage in cytosolic α-mannosidase (Man2c1)-deficient mice. 24550399 9 36 theme compounds 1382:1390 arg1 glycogen 1396:1403 glycogen 1396:1403 glycogen 1396:1403 Liver tissue is characterized by groups of hepatocytes with increased content of mannosyl compounds and glycogen, some of them undergoing degeneration by hydropic swelling. 24550399 9 36 theme compounds 1382:1390 arg1 content 1362:1368 increased content 1352:1368 increased content of mannosyl compounds 1352:1390 Liver tissue is characterized by groups of hepatocytes with increased content of mannosyl compounds and glycogen, some of them undergoing degeneration by hydropic swelling. 24550399 8 37 from saccharides 1173:1183 arg1 cytoplasm 1224:1232 their apical cytoplasm 1211:1232 their apical cytoplasm 1211:1232 Enterocytes of the small intestine accumulate mannose-containing saccharides and glycogen particles in their apical cytoplasm as well as large clear vacuoles in retronuclear position. 24550399 10 38 theme saccharides 1537:1547 arg1 presence 1506:1513 the presence 1502:1513 the presence of mannose-containing saccharides in the epithelium of proximal kidney tubules 1502:1592 In addition, lectin screening showed the presence of mannose-containing saccharides in the epithelium of proximal kidney tubules, whereas scattered glomeruli appeared collapsed or featured signs of fibrosis along Bowman's capsule. 24550399 10 39 theme kidney 1579:1584 arg1 tubules 1586:1592 proximal kidney tubules 1570:1592 proximal kidney tubules 1570:1592 In addition, lectin screening showed the presence of mannose-containing saccharides in the epithelium of proximal kidney tubules, whereas scattered glomeruli appeared collapsed or featured signs of fibrosis along Bowman's capsule. 24550399 0 40 theme cytosolic 59:67 arg1 mice 102:105 cytosolic α-mannosidase (Man2c1)-deficient mice 59:105 cytosolic α-mannosidase (Man2c1)-deficient mice 59:105 Accumulation of free oligosaccharides and tissue damage in cytosolic α-mannosidase (Man2c1)-deficient mice. 24550399 11 41 theme moderate 1709:1716 arg1 enrichment 1718:1727 a moderate enrichment 1707:1727 a moderate enrichment of mannosyl compounds and glycogen 1707:1762 Except for a moderate enrichment of mannosyl compounds and glycogen, heterozygous mice were normal, arguing against possible toxic effects of truncated Man2c1. 24550399 3 42 theme responsible 473:483 arg1 α-Mannosidase 436:448 α-Mannosidase 436:448 α-Mannosidase (MAN2C1) 436:457 α-Mannosidase (MAN2C1) is the enzyme responsible for the partial demannosylation occurring in the cytosol. 24550399 3 42 theme responsible 473:483 arg1 enzyme 466:471 the enzyme 462:471 the enzyme responsible for the partial demannosylation occurring in the cytosol 462:540 α-Mannosidase (MAN2C1) is the enzyme responsible for the partial demannosylation occurring in the cytosol. 24550399 0 43 theme damage 49:54 arg1 Accumulation 0:11 Accumulation 0:11 Accumulation of free oligosaccharides and tissue damage in cytosolic α-mannosidase (Man2c1)-deficient mice. 0:106 Accumulation of free oligosaccharides and tissue damage in cytosolic α-mannosidase (Man2c1)-deficient mice. 24550399 6 44 theme Increased 829:837 arg1 amounts 839:845 Increased amounts 829:845 Increased amounts of Man(8-9)GlcNAc oligosaccharides 829:880 Increased amounts of Man(8-9)GlcNAc oligosaccharides were recognized in all analyzed KO tissues. 24550399 6 44 theme Increased 829:837 arg1 oligosaccharides 865:880 Man(8-9)GlcNAc oligosaccharides 850:880 Man(8-9)GlcNAc oligosaccharides 850:880 Increased amounts of Man(8-9)GlcNAc oligosaccharides were recognized in all analyzed KO tissues. 24550399 4 45 theme MAN2C1 591:596 arg1 expression 598:607 MAN2C1 expression 591:607 MAN2C1 expression 591:607 It has been demonstrated that the inhibition of MAN2C1 expression induces accumulation of Man(8-9)GlcNAc oligosaccharides and apoptosis in vitro. 24550399 10 46 theme scattered 1603:1611 arg1 glomeruli 1613:1621 scattered glomeruli 1603:1621 scattered glomeruli 1603:1621 In addition, lectin screening showed the presence of mannose-containing saccharides in the epithelium of proximal kidney tubules, whereas scattered glomeruli appeared collapsed or featured signs of fibrosis along Bowman's capsule. 24550399 8 47 theme intestine 1133:1141 arg1 Enterocytes 1108:1118 Enterocytes 1108:1118 Enterocytes of the small intestine 1108:1141 Enterocytes of the small intestine accumulate mannose-containing saccharides and glycogen particles in their apical cytoplasm as well as large clear vacuoles in retronuclear position. 24550399 6 48 theme KO 914:915 arg1 tissues 917:923 all analyzed KO tissues 901:923 all analyzed KO tissues 901:923 Increased amounts of Man(8-9)GlcNAc oligosaccharides were recognized in all analyzed KO tissues. 24550399 9 49 theme hydropic 1446:1453 arg1 swelling 1455:1462 hydropic swelling 1446:1462 hydropic swelling 1446:1462 Liver tissue is characterized by groups of hepatocytes with increased content of mannosyl compounds and glycogen, some of them undergoing degeneration by hydropic swelling. 24550399 8 50 theme mannose-containing 1154:1171 arg1 saccharides 1173:1183 mannose-containing saccharides 1154:1183 mannose-containing saccharides 1154:1183 Enterocytes of the small intestine accumulate mannose-containing saccharides and glycogen particles in their apical cytoplasm as well as large clear vacuoles in retronuclear position. 24550399 1 51 theme reticulum-associated 248:267 arg1 process 281:287 the endoplasmic reticulum-associated degradation process 232:287 the endoplasmic reticulum-associated degradation process 232:287 Free Man(7-9)GlcNAc2 is released during the biosynthesis pathway of N-linked glycans or from misfolded glycoproteins during the endoplasmic reticulum-associated degradation process and are reduced to Man5GlcNAc in the cytosol. 24550399 11 52 theme mannosyl 1732:1739 arg1 compounds 1741:1749 mannosyl compounds 1732:1749 mannosyl compounds 1732:1749 Except for a moderate enrichment of mannosyl compounds and glycogen, heterozygous mice were normal, arguing against possible toxic effects of truncated Man2c1. 24550399 6 53 theme oligosaccharides 865:880 arg1 amounts 839:845 Increased amounts 829:845 Increased amounts of Man(8-9)GlcNAc oligosaccharides 829:880 Increased amounts of Man(8-9)GlcNAc oligosaccharides were recognized in all analyzed KO tissues. 24550399 6 53 theme oligosaccharides 865:880 arg1 oligosaccharides 865:880 Man(8-9)GlcNAc oligosaccharides 850:880 Man(8-9)GlcNAc oligosaccharides 850:880 Increased amounts of Man(8-9)GlcNAc oligosaccharides were recognized in all analyzed KO tissues. 24550399 10 54 theme fibrosis 1663:1670 arg1 signs 1654:1658 collapsed or featured signs 1632:1658 collapsed or featured signs of fibrosis 1632:1670 In addition, lectin screening showed the presence of mannose-containing saccharides in the epithelium of proximal kidney tubules, whereas scattered glomeruli appeared collapsed or featured signs of fibrosis along Bowman's capsule. 24550399 7 55 theme white 1087:1091 arg1 matter 1093:1098 telencephalic white matter 1073:1098 major telencephalic white matter tracts 1067:1105 Histological analysis of the CNS revealed neuronal and glial degeneration with formation of multiple vacuoles in deep neocortical layers and major telencephalic white matter tracts. 24550399 1 56 theme biosynthesis 152:163 arg1 pathway 165:171 the biosynthesis pathway 148:171 the biosynthesis pathway of N-linked glycans 148:191 Free Man(7-9)GlcNAc2 is released during the biosynthesis pathway of N-linked glycans or from misfolded glycoproteins during the endoplasmic reticulum-associated degradation process and are reduced to Man5GlcNAc in the cytosol. 24550399 4 57 theme oligosaccharides 648:663 arg1 apoptosis 669:677 apoptosis 669:677 apoptosis 669:677 It has been demonstrated that the inhibition of MAN2C1 expression induces accumulation of Man(8-9)GlcNAc oligosaccharides and apoptosis in vitro. 24550399 4 57 theme oligosaccharides 648:663 arg1 accumulation 617:628 accumulation 617:628 accumulation of Man(8-9)GlcNAc oligosaccharides 617:663 It has been demonstrated that the inhibition of MAN2C1 expression induces accumulation of Man(8-9)GlcNAc oligosaccharides and apoptosis in vitro. 24550399 7 58 theme major 1067:1071 arg1 tracts 1100:1105 major telencephalic white matter tracts 1067:1105 major telencephalic white matter tracts 1067:1105 Histological analysis of the CNS revealed neuronal and glial degeneration with formation of multiple vacuoles in deep neocortical layers and major telencephalic white matter tracts. 24550399 8 59 theme retronuclear 1269:1280 arg1 position 1282:1289 retronuclear position 1269:1289 retronuclear position 1269:1289 Enterocytes of the small intestine accumulate mannose-containing saccharides and glycogen particles in their apical cytoplasm as well as large clear vacuoles in retronuclear position. 24550399 1 60 theme glycans 185:191 arg1 pathway 165:171 the biosynthesis pathway 148:171 the biosynthesis pathway of N-linked glycans 148:191 Free Man(7-9)GlcNAc2 is released during the biosynthesis pathway of N-linked glycans or from misfolded glycoproteins during the endoplasmic reticulum-associated degradation process and are reduced to Man5GlcNAc in the cytosol. 24550399 7 61 theme deep 1039:1042 arg1 layers 1056:1061 deep neocortical layers 1039:1061 deep neocortical layers 1039:1061 Histological analysis of the CNS revealed neuronal and glial degeneration with formation of multiple vacuoles in deep neocortical layers and major telencephalic white matter tracts. 24550399 7 62 theme multiple 1018:1025 arg1 vacuoles 1027:1034 multiple vacuoles 1018:1034 multiple vacuoles 1018:1034 Histological analysis of the CNS revealed neuronal and glial degeneration with formation of multiple vacuoles in deep neocortical layers and major telencephalic white matter tracts. 24550399 1 63 theme Free 108:111 arg1 GlcNAc2 121:127 Free Man(7-9)GlcNAc2 108:127 Free Man(7-9)GlcNAc2 108:127 Free Man(7-9)GlcNAc2 is released during the biosynthesis pathway of N-linked glycans or from misfolded glycoproteins during the endoplasmic reticulum-associated degradation process and are reduced to Man5GlcNAc in the cytosol. 24550399 8 64 theme large 1245:1249 arg1 vacuoles 1257:1264 large clear vacuoles 1245:1264 mannose-containing saccharides and glycogen particles in their apical cytoplasm as well as large clear vacuoles 1154:1264 Enterocytes of the small intestine accumulate mannose-containing saccharides and glycogen particles in their apical cytoplasm as well as large clear vacuoles in retronuclear position. 24550399 7 65 theme vacuoles 1027:1034 arg1 formation 1005:1013 formation 1005:1013 formation of multiple vacuoles 1005:1034 Histological analysis of the CNS revealed neuronal and glial degeneration with formation of multiple vacuoles in deep neocortical layers and major telencephalic white matter tracts. 24550399 9 66 theme Liver 1292:1296 arg1 tissue 1298:1303 Liver tissue 1292:1303 Liver tissue 1292:1303 Liver tissue is characterized by groups of hepatocytes with increased content of mannosyl compounds and glycogen, some of them undergoing degeneration by hydropic swelling. 24550399 8 67 from vacuoles 1257:1264 arg1 cytoplasm 1224:1232 their apical cytoplasm 1211:1232 their apical cytoplasm 1211:1232 Enterocytes of the small intestine accumulate mannose-containing saccharides and glycogen particles in their apical cytoplasm as well as large clear vacuoles in retronuclear position. 24550399 9 68 with hepatocytes 1335:1345 arg1 glycogen 1396:1403 glycogen 1396:1403 glycogen 1396:1403 Liver tissue is characterized by groups of hepatocytes with increased content of mannosyl compounds and glycogen, some of them undergoing degeneration by hydropic swelling. 24550399 9 68 with hepatocytes 1335:1345 arg1 content 1362:1368 increased content 1352:1368 increased content of mannosyl compounds 1352:1390 Liver tissue is characterized by groups of hepatocytes with increased content of mannosyl compounds and glycogen, some of them undergoing degeneration by hydropic swelling. 24550399 11 69 theme possible 1812:1819 arg1 effects 1827:1833 possible toxic effects 1812:1833 possible toxic effects of truncated Man2c1 1812:1853 Except for a moderate enrichment of mannosyl compounds and glycogen, heterozygous mice were normal, arguing against possible toxic effects of truncated Man2c1. 24550399 5 70 theme α-mannosidase 754:766 arg1 activity 768:775 cytosolic α-mannosidase activity 744:775 cytosolic α-mannosidase activity 744:775 We investigated the consequences caused by the lack of cytosolic α-mannosidase activity in vivo by the generation of Man2c1-deficient mice. 24550399 10 71 theme lectin 1478:1483 arg1 screening 1485:1493 lectin screening 1478:1493 lectin screening 1478:1493 In addition, lectin screening showed the presence of mannose-containing saccharides in the epithelium of proximal kidney tubules, whereas scattered glomeruli appeared collapsed or featured signs of fibrosis along Bowman's capsule. 24550399 11 72 theme truncated 1838:1846 arg1 Man2c1 1848:1853 truncated Man2c1 1838:1853 truncated Man2c1 1838:1853 Except for a moderate enrichment of mannosyl compounds and glycogen, heterozygous mice were normal, arguing against possible toxic effects of truncated Man2c1. 24550399 0 73 theme -deficient 91:100 arg1 mice 102:105 cytosolic α-mannosidase (Man2c1)-deficient mice 59:105 cytosolic α-mannosidase (Man2c1)-deficient mice 59:105 Accumulation of free oligosaccharides and tissue damage in cytosolic α-mannosidase (Man2c1)-deficient mice. 24550399 1 74 link N-linked 176:183 arg1 glycans 185:191 N-linked glycans 176:191 N-linked glycans 176:191 Free Man(7-9)GlcNAc2 is released during the biosynthesis pathway of N-linked glycans or from misfolded glycoproteins during the endoplasmic reticulum-associated degradation process and are reduced to Man5GlcNAc in the cytosol. 24550399 1 75 gly glycoproteins 211:223 arg1 glycoproteins 211:223 misfolded glycoproteins 201:223 misfolded glycoproteins 201:223 Free Man(7-9)GlcNAc2 is released during the biosynthesis pathway of N-linked glycans or from misfolded glycoproteins during the endoplasmic reticulum-associated degradation process and are reduced to Man5GlcNAc in the cytosol. 24550399 0 76 theme oligosaccharides 21:36 arg1 Accumulation 0:11 Accumulation 0:11 Accumulation of free oligosaccharides and tissue damage in cytosolic α-mannosidase (Man2c1)-deficient mice. 0:106 Accumulation of free oligosaccharides and tissue damage in cytosolic α-mannosidase (Man2c1)-deficient mice. 24550399 9 77 theme mannosyl 1373:1380 arg1 compounds 1382:1390 mannosyl compounds 1373:1390 mannosyl compounds 1373:1390 Liver tissue is characterized by groups of hepatocytes with increased content of mannosyl compounds and glycogen, some of them undergoing degeneration by hydropic swelling. 24550399 11 78 theme glycogen 1755:1762 arg1 enrichment 1718:1727 a moderate enrichment 1707:1727 a moderate enrichment of mannosyl compounds and glycogen 1707:1762 Except for a moderate enrichment of mannosyl compounds and glycogen, heterozygous mice were normal, arguing against possible toxic effects of truncated Man2c1. 24550399 0 79 theme tissue 42:47 arg1 damage 49:54 tissue damage 42:54 tissue damage 42:54 Accumulation of free oligosaccharides and tissue damage in cytosolic α-mannosidase (Man2c1)-deficient mice. 24550399 12 80 theme free 1930:1933 arg1 oligosaccharides 1935:1950 free oligosaccharides 1930:1950 free oligosaccharides 1930:1950 These findings confirm the key role played by Man2c1 in the catabolism of free oligosaccharides. 24550399 10 81 theme mannose-containing 1518:1535 arg1 saccharides 1537:1547 mannose-containing saccharides 1518:1547 mannose-containing saccharides 1518:1547 In addition, lectin screening showed the presence of mannose-containing saccharides in the epithelium of proximal kidney tubules, whereas scattered glomeruli appeared collapsed or featured signs of fibrosis along Bowman's capsule. 24550399 11 82 theme compounds 1741:1749 arg1 enrichment 1718:1727 a moderate enrichment 1707:1727 a moderate enrichment of mannosyl compounds and glycogen 1707:1762 Except for a moderate enrichment of mannosyl compounds and glycogen, heterozygous mice were normal, arguing against possible toxic effects of truncated Man2c1. 24550399 6 83 theme Man 850:852 arg1 oligosaccharides 865:880 Man(8-9)GlcNAc oligosaccharides 850:880 Man(8-9)GlcNAc oligosaccharides 850:880 Increased amounts of Man(8-9)GlcNAc oligosaccharides were recognized in all analyzed KO tissues. 24550399 10 84 theme proximal 1570:1577 arg1 tubules 1586:1592 proximal kidney tubules 1570:1592 proximal kidney tubules 1570:1592 In addition, lectin screening showed the presence of mannose-containing saccharides in the epithelium of proximal kidney tubules, whereas scattered glomeruli appeared collapsed or featured signs of fibrosis along Bowman's capsule. 24550399 8 85 theme small 1127:1131 arg1 intestine 1133:1141 the small intestine 1123:1141 the small intestine 1123:1141 Enterocytes of the small intestine accumulate mannose-containing saccharides and glycogen particles in their apical cytoplasm as well as large clear vacuoles in retronuclear position. 24550399 8 86 from particles 1198:1206 arg1 cytoplasm 1224:1232 their apical cytoplasm 1211:1232 their apical cytoplasm 1211:1232 Enterocytes of the small intestine accumulate mannose-containing saccharides and glycogen particles in their apical cytoplasm as well as large clear vacuoles in retronuclear position. 24550399 12 87 theme key 1883:1885 arg1 role 1887:1890 the key role 1879:1890 the key role played by Man2c1 in the catabolism of free oligosaccharides 1879:1950 These findings confirm the key role played by Man2c1 in the catabolism of free oligosaccharides. 24550399 4 88 theme expression 598:607 arg1 inhibition 577:586 the inhibition 573:586 the inhibition of MAN2C1 expression 573:607 It has been demonstrated that the inhibition of MAN2C1 expression induces accumulation of Man(8-9)GlcNAc oligosaccharides and apoptosis in vitro. 24550399 11 89 theme heterozygous 1765:1776 arg1 mice 1778:1781 heterozygous mice 1765:1781 heterozygous mice 1765:1781 Except for a moderate enrichment of mannosyl compounds and glycogen, heterozygous mice were normal, arguing against possible toxic effects of truncated Man2c1. 24550399 1 90 theme misfolded 201:209 arg1 glycoproteins 211:223 misfolded glycoproteins 201:223 misfolded glycoproteins 201:223 Free Man(7-9)GlcNAc2 is released during the biosynthesis pathway of N-linked glycans or from misfolded glycoproteins during the endoplasmic reticulum-associated degradation process and are reduced to Man5GlcNAc in the cytosol. 24550399 2 91 theme free 349:352 arg1 oligosaccharides 354:369 free oligosaccharides 349:369 free oligosaccharides 349:369 In this form, free oligosaccharides can be transferred into the lysosomes to be degraded completely. 26414071 0 0 theme Fucosylation 94:105 arg1 Inhibitor 50:58 a Metabolically Incorporated Inhibitor 21:58 a Metabolically Incorporated Inhibitor of Plant Cell Wall Polysaccharide Fucosylation 21:105 2-Fluoro-L-Fucose Is a Metabolically Incorporated Inhibitor of Plant Cell Wall Polysaccharide Fucosylation. 26414071 0 0 theme Fucosylation 94:105 arg1 2-Fluoro-L-Fucose 0:16 2-Fluoro-L-Fucose 0:16 2-Fluoro-L-Fucose 0:16 2-Fluoro-L-Fucose Is a Metabolically Incorporated Inhibitor of Plant Cell Wall Polysaccharide Fucosylation. 26414071 1 1 theme arabinogalactan 336:350 arg1 proteins 352:359 arabinogalactan proteins 336:359 arabinogalactan proteins 336:359 The monosaccharide L-fucose (L-Fuc) is a common component of plant cell wall polysaccharides and other plant glycans, including the hemicellulose xyloglucan, pectic rhamnogalacturonan-I (RG-I) and rhamnogalacturonan-II (RG-II), arabinogalactan proteins, and N-linked glycans. 26414071 4 2 theme altered 903:909 arg1 morphology 916:925 altered root morphology 903:925 altered root morphology 903:925 2-fluoro-L-fucose (2F-Fuc) analogs caused severe growth phenotypes when applied to Arabidopsis seedlings, including reduced root growth and altered root morphology. 26414071 6 3 theme L-Fuc 1353:1357 arg1 incorporation 1336:1348 the incorporation 1332:1348 the incorporation of L-Fuc into these polysaccharides 1332:1384 The L-Fuc content of cell wall matrix polysaccharides was reduced in plants treated with 2F-Fuc, suggesting that this molecule inhibits the incorporation of L-Fuc into these polysaccharides. 26414071 5 4 theme phenotypic 934:943 arg1 defects 945:951 These phenotypic defects 928:951 These phenotypic defects 928:951 These phenotypic defects were dependent upon the L-Fuc salvage pathway enzyme L-Fucose Kinase/ GDP-L-Fucose Pyrophosphorylase (FKGP), suggesting that 2F-Fuc is metabolically converted to the sugar nucleotide GDP-2F-Fuc, which serves as the active inhibitory molecule. 26414071 0 5 theme Polysaccharide 79:92 arg1 Fucosylation 94:105 Plant Cell Wall Polysaccharide Fucosylation 63:105 Plant Cell Wall Polysaccharide Fucosylation 63:105 2-Fluoro-L-Fucose Is a Metabolically Incorporated Inhibitor of Plant Cell Wall Polysaccharide Fucosylation. 26414071 8 6 theme chemical 1796:1803 arg1 monosaccharides 1758:1772 other 2-fluorinated monosaccharides 1738:1772 other 2-fluorinated monosaccharides 1738:1772 Overall, the results presented here suggest that 2F-Fuc is a metabolically incorporated inhibitor of plant cellular fucosylation events, and potentially suggest that other 2-fluorinated monosaccharides could serve as useful chemical probes for the inhibition of cell wall polysaccharide biosynthesis. 26414071 8 6 theme chemical 1796:1803 arg1 probes 1805:1810 useful chemical probes 1789:1810 useful chemical probes for the inhibition of cell wall polysaccharide biosynthesis 1789:1870 Overall, the results presented here suggest that 2F-Fuc is a metabolically incorporated inhibitor of plant cellular fucosylation events, and potentially suggest that other 2-fluorinated monosaccharides could serve as useful chemical probes for the inhibition of cell wall polysaccharide biosynthesis. 26414071 2 7 theme cell 528:531 arg1 biosynthesis 553:564 plant cell wall polysaccharide biosynthesis 522:564 plant cell wall polysaccharide biosynthesis 522:564 Mutations compromising the biosynthesis of many plant cell wall polysaccharides are lethal, and as a result, small molecule inhibitors of plant cell wall polysaccharide biosynthesis have been developed because these molecules can be applied at defined concentrations and developmental stages. 26414071 3 8 theme novel 708:712 arg1 inhibitors 729:738 novel small molecule inhibitors 708:738 novel small molecule inhibitors of plant fucosylation 708:760 In this study, we characterize novel small molecule inhibitors of plant fucosylation. 26414071 5 9 theme L-Fucose 1006:1013 arg1 FKGP 1055:1058 FKGP 1055:1058 FKGP 1055:1058 These phenotypic defects were dependent upon the L-Fuc salvage pathway enzyme L-Fucose Kinase/ GDP-L-Fucose Pyrophosphorylase (FKGP), suggesting that 2F-Fuc is metabolically converted to the sugar nucleotide GDP-2F-Fuc, which serves as the active inhibitory molecule. 26414071 5 9 theme L-Fucose 1006:1013 arg1 Pyrophosphorylase 1036:1052 the L-Fuc salvage pathway enzyme L-Fucose Kinase/ GDP-L-Fucose Pyrophosphorylase 973:1052 the L-Fuc salvage pathway enzyme L-Fucose Kinase/ GDP-L-Fucose Pyrophosphorylase (FKGP) 973:1059 These phenotypic defects were dependent upon the L-Fuc salvage pathway enzyme L-Fucose Kinase/ GDP-L-Fucose Pyrophosphorylase (FKGP), suggesting that 2F-Fuc is metabolically converted to the sugar nucleotide GDP-2F-Fuc, which serves as the active inhibitory molecule. 26414071 7 10 theme acid 1514:1517 arg1 application 1493:1503 the exogenous application 1479:1503 the exogenous application of boric acid 1479:1517 Additionally, phenotypic defects induced by 2F-Fuc treatment could be partially relieved by the exogenous application of boric acid, suggesting that 2F-Fuc inhibits RG-II biosynthesis. 26414071 1 11 theme pectic 266:271 arg1 RG-I 295:298 RG-I 295:298 RG-I 295:298 The monosaccharide L-fucose (L-Fuc) is a common component of plant cell wall polysaccharides and other plant glycans, including the hemicellulose xyloglucan, pectic rhamnogalacturonan-I (RG-I) and rhamnogalacturonan-II (RG-II), arabinogalactan proteins, and N-linked glycans. 26414071 1 11 theme pectic 266:271 arg1 rhamnogalacturonan-I 273:292 pectic rhamnogalacturonan-I 266:292 pectic rhamnogalacturonan-I (RG-I) 266:299 The monosaccharide L-fucose (L-Fuc) is a common component of plant cell wall polysaccharides and other plant glycans, including the hemicellulose xyloglucan, pectic rhamnogalacturonan-I (RG-I) and rhamnogalacturonan-II (RG-II), arabinogalactan proteins, and N-linked glycans. 26414071 2 12 theme plant 522:526 arg1 biosynthesis 553:564 plant cell wall polysaccharide biosynthesis 522:564 plant cell wall polysaccharide biosynthesis 522:564 Mutations compromising the biosynthesis of many plant cell wall polysaccharides are lethal, and as a result, small molecule inhibitors of plant cell wall polysaccharide biosynthesis have been developed because these molecules can be applied at defined concentrations and developmental stages. 26414071 3 13 theme plant 743:747 arg1 fucosylation 749:760 plant fucosylation 743:760 plant fucosylation 743:760 In this study, we characterize novel small molecule inhibitors of plant fucosylation. 26414071 4 14 theme root 911:914 arg1 morphology 916:925 altered root morphology 903:925 altered root morphology 903:925 2-fluoro-L-fucose (2F-Fuc) analogs caused severe growth phenotypes when applied to Arabidopsis seedlings, including reduced root growth and altered root morphology. 26414071 5 15 theme Kinase/ 1015:1021 arg1 FKGP 1055:1058 FKGP 1055:1058 FKGP 1055:1058 These phenotypic defects were dependent upon the L-Fuc salvage pathway enzyme L-Fucose Kinase/ GDP-L-Fucose Pyrophosphorylase (FKGP), suggesting that 2F-Fuc is metabolically converted to the sugar nucleotide GDP-2F-Fuc, which serves as the active inhibitory molecule. 26414071 5 15 theme Kinase/ 1015:1021 arg1 Pyrophosphorylase 1036:1052 the L-Fuc salvage pathway enzyme L-Fucose Kinase/ GDP-L-Fucose Pyrophosphorylase 973:1052 the L-Fuc salvage pathway enzyme L-Fucose Kinase/ GDP-L-Fucose Pyrophosphorylase (FKGP) 973:1059 These phenotypic defects were dependent upon the L-Fuc salvage pathway enzyme L-Fucose Kinase/ GDP-L-Fucose Pyrophosphorylase (FKGP), suggesting that 2F-Fuc is metabolically converted to the sugar nucleotide GDP-2F-Fuc, which serves as the active inhibitory molecule. 26414071 1 16 theme N-linked 366:373 arg1 glycans 375:381 N-linked glycans 366:381 N-linked glycans 366:381 The monosaccharide L-fucose (L-Fuc) is a common component of plant cell wall polysaccharides and other plant glycans, including the hemicellulose xyloglucan, pectic rhamnogalacturonan-I (RG-I) and rhamnogalacturonan-II (RG-II), arabinogalactan proteins, and N-linked glycans. 26414071 4 17 theme reduced 879:885 arg1 growth 892:897 reduced root growth 879:897 reduced root growth 879:897 2-fluoro-L-fucose (2F-Fuc) analogs caused severe growth phenotypes when applied to Arabidopsis seedlings, including reduced root growth and altered root morphology. 26414071 2 18 theme plant 432:436 arg1 polysaccharides 448:462 many plant cell wall polysaccharides 427:462 many plant cell wall polysaccharides 427:462 Mutations compromising the biosynthesis of many plant cell wall polysaccharides are lethal, and as a result, small molecule inhibitors of plant cell wall polysaccharide biosynthesis have been developed because these molecules can be applied at defined concentrations and developmental stages. 26414071 4 19 theme severe 805:810 arg1 phenotypes 819:828 severe growth phenotypes 805:828 severe growth phenotypes 805:828 2-fluoro-L-fucose (2F-Fuc) analogs caused severe growth phenotypes when applied to Arabidopsis seedlings, including reduced root growth and altered root morphology. 26414071 1 20 theme plant 169:173 arg1 polysaccharides 185:199 plant cell wall polysaccharides 169:199 plant cell wall polysaccharides 169:199 The monosaccharide L-fucose (L-Fuc) is a common component of plant cell wall polysaccharides and other plant glycans, including the hemicellulose xyloglucan, pectic rhamnogalacturonan-I (RG-I) and rhamnogalacturonan-II (RG-II), arabinogalactan proteins, and N-linked glycans. 26414071 8 21 theme other 1738:1742 arg1 monosaccharides 1758:1772 other 2-fluorinated monosaccharides 1738:1772 other 2-fluorinated monosaccharides 1738:1772 Overall, the results presented here suggest that 2F-Fuc is a metabolically incorporated inhibitor of plant cellular fucosylation events, and potentially suggest that other 2-fluorinated monosaccharides could serve as useful chemical probes for the inhibition of cell wall polysaccharide biosynthesis. 26414071 8 21 theme other 1738:1742 arg1 probes 1805:1810 useful chemical probes 1789:1810 useful chemical probes for the inhibition of cell wall polysaccharide biosynthesis 1789:1870 Overall, the results presented here suggest that 2F-Fuc is a metabolically incorporated inhibitor of plant cellular fucosylation events, and potentially suggest that other 2-fluorinated monosaccharides could serve as useful chemical probes for the inhibition of cell wall polysaccharide biosynthesis. 26414071 5 22 theme L-Fuc 977:981 arg1 FKGP 1055:1058 FKGP 1055:1058 FKGP 1055:1058 These phenotypic defects were dependent upon the L-Fuc salvage pathway enzyme L-Fucose Kinase/ GDP-L-Fucose Pyrophosphorylase (FKGP), suggesting that 2F-Fuc is metabolically converted to the sugar nucleotide GDP-2F-Fuc, which serves as the active inhibitory molecule. 26414071 5 22 theme L-Fuc 977:981 arg1 Pyrophosphorylase 1036:1052 the L-Fuc salvage pathway enzyme L-Fucose Kinase/ GDP-L-Fucose Pyrophosphorylase 973:1052 the L-Fuc salvage pathway enzyme L-Fucose Kinase/ GDP-L-Fucose Pyrophosphorylase (FKGP) 973:1059 These phenotypic defects were dependent upon the L-Fuc salvage pathway enzyme L-Fucose Kinase/ GDP-L-Fucose Pyrophosphorylase (FKGP), suggesting that 2F-Fuc is metabolically converted to the sugar nucleotide GDP-2F-Fuc, which serves as the active inhibitory molecule. 26414071 1 23 theme cell 175:178 arg1 polysaccharides 185:199 plant cell wall polysaccharides 169:199 plant cell wall polysaccharides 169:199 The monosaccharide L-fucose (L-Fuc) is a common component of plant cell wall polysaccharides and other plant glycans, including the hemicellulose xyloglucan, pectic rhamnogalacturonan-I (RG-I) and rhamnogalacturonan-II (RG-II), arabinogalactan proteins, and N-linked glycans. 26414071 2 24 theme defined 628:634 arg1 concentrations 636:649 defined concentrations 628:649 defined concentrations 628:649 Mutations compromising the biosynthesis of many plant cell wall polysaccharides are lethal, and as a result, small molecule inhibitors of plant cell wall polysaccharide biosynthesis have been developed because these molecules can be applied at defined concentrations and developmental stages. 26414071 2 25 theme molecule 499:506 arg1 result 485:490 a result 483:490 a result 483:490 Mutations compromising the biosynthesis of many plant cell wall polysaccharides are lethal, and as a result, small molecule inhibitors of plant cell wall polysaccharide biosynthesis have been developed because these molecules can be applied at defined concentrations and developmental stages. 26414071 2 25 theme molecule 499:506 arg1 inhibitors 508:517 small molecule inhibitors 493:517 small molecule inhibitors of plant cell wall polysaccharide biosynthesis 493:564 Mutations compromising the biosynthesis of many plant cell wall polysaccharides are lethal, and as a result, small molecule inhibitors of plant cell wall polysaccharide biosynthesis have been developed because these molecules can be applied at defined concentrations and developmental stages. 26414071 4 26 theme 2-fluoro-L-fucose 763:779 arg1 analogs 790:796 2-fluoro-L-fucose (2F-Fuc) analogs 763:796 2-fluoro-L-fucose (2F-Fuc) analogs 763:796 2-fluoro-L-fucose (2F-Fuc) analogs caused severe growth phenotypes when applied to Arabidopsis seedlings, including reduced root growth and altered root morphology. 26414071 1 27 link N-linked 366:373 arg1 glycans 375:381 N-linked glycans 366:381 N-linked glycans 366:381 The monosaccharide L-fucose (L-Fuc) is a common component of plant cell wall polysaccharides and other plant glycans, including the hemicellulose xyloglucan, pectic rhamnogalacturonan-I (RG-I) and rhamnogalacturonan-II (RG-II), arabinogalactan proteins, and N-linked glycans. 26414071 1 28 theme wall 180:183 arg1 polysaccharides 185:199 plant cell wall polysaccharides 169:199 plant cell wall polysaccharides 169:199 The monosaccharide L-fucose (L-Fuc) is a common component of plant cell wall polysaccharides and other plant glycans, including the hemicellulose xyloglucan, pectic rhamnogalacturonan-I (RG-I) and rhamnogalacturonan-II (RG-II), arabinogalactan proteins, and N-linked glycans. 26414071 7 29 theme boric 1508:1512 arg1 acid 1514:1517 boric acid 1508:1517 boric acid 1508:1517 Additionally, phenotypic defects induced by 2F-Fuc treatment could be partially relieved by the exogenous application of boric acid, suggesting that 2F-Fuc inhibits RG-II biosynthesis. 26414071 4 30 theme root 887:890 arg1 growth 892:897 reduced root growth 879:897 reduced root growth 879:897 2-fluoro-L-fucose (2F-Fuc) analogs caused severe growth phenotypes when applied to Arabidopsis seedlings, including reduced root growth and altered root morphology. 26414071 5 31 theme salvage 983:989 arg1 FKGP 1055:1058 FKGP 1055:1058 FKGP 1055:1058 These phenotypic defects were dependent upon the L-Fuc salvage pathway enzyme L-Fucose Kinase/ GDP-L-Fucose Pyrophosphorylase (FKGP), suggesting that 2F-Fuc is metabolically converted to the sugar nucleotide GDP-2F-Fuc, which serves as the active inhibitory molecule. 26414071 5 31 theme salvage 983:989 arg1 Pyrophosphorylase 1036:1052 the L-Fuc salvage pathway enzyme L-Fucose Kinase/ GDP-L-Fucose Pyrophosphorylase 973:1052 the L-Fuc salvage pathway enzyme L-Fucose Kinase/ GDP-L-Fucose Pyrophosphorylase (FKGP) 973:1059 These phenotypic defects were dependent upon the L-Fuc salvage pathway enzyme L-Fucose Kinase/ GDP-L-Fucose Pyrophosphorylase (FKGP), suggesting that 2F-Fuc is metabolically converted to the sugar nucleotide GDP-2F-Fuc, which serves as the active inhibitory molecule. 26414071 7 32 theme 2F-Fuc 1431:1436 arg1 treatment 1438:1446 2F-Fuc treatment 1431:1446 2F-Fuc treatment 1431:1446 Additionally, phenotypic defects induced by 2F-Fuc treatment could be partially relieved by the exogenous application of boric acid, suggesting that 2F-Fuc inhibits RG-II biosynthesis. 26414071 1 33 theme polysaccharides 185:199 arg1 component 156:164 a common component 147:164 a common component of plant cell wall polysaccharides and other plant glycans, including the hemicellulose xyloglucan, pectic rhamnogalacturonan-I (RG-I) and rhamnogalacturonan-II (RG-II), arabinogalactan proteins, and N-linked glycans 147:381 The monosaccharide L-fucose (L-Fuc) is a common component of plant cell wall polysaccharides and other plant glycans, including the hemicellulose xyloglucan, pectic rhamnogalacturonan-I (RG-I) and rhamnogalacturonan-II (RG-II), arabinogalactan proteins, and N-linked glycans. 26414071 1 33 theme polysaccharides 185:199 arg1 L-fucose 127:134 The monosaccharide L-fucose 108:134 The monosaccharide L-fucose (L-Fuc) 108:142 The monosaccharide L-fucose (L-Fuc) is a common component of plant cell wall polysaccharides and other plant glycans, including the hemicellulose xyloglucan, pectic rhamnogalacturonan-I (RG-I) and rhamnogalacturonan-II (RG-II), arabinogalactan proteins, and N-linked glycans. 26414071 2 34 theme polysaccharides 448:462 arg1 biosynthesis 411:422 the biosynthesis 407:422 the biosynthesis of many plant cell wall polysaccharides 407:462 Mutations compromising the biosynthesis of many plant cell wall polysaccharides are lethal, and as a result, small molecule inhibitors of plant cell wall polysaccharide biosynthesis have been developed because these molecules can be applied at defined concentrations and developmental stages. 26414071 7 35 theme exogenous 1483:1491 arg1 application 1493:1503 the exogenous application 1479:1503 the exogenous application of boric acid 1479:1517 Additionally, phenotypic defects induced by 2F-Fuc treatment could be partially relieved by the exogenous application of boric acid, suggesting that 2F-Fuc inhibits RG-II biosynthesis. 26414071 2 36 theme developmental 655:667 arg1 stages 669:674 developmental stages 655:674 developmental stages 655:674 Mutations compromising the biosynthesis of many plant cell wall polysaccharides are lethal, and as a result, small molecule inhibitors of plant cell wall polysaccharide biosynthesis have been developed because these molecules can be applied at defined concentrations and developmental stages. 26414071 1 37 theme monosaccharide 112:125 arg1 component 156:164 a common component 147:164 a common component of plant cell wall polysaccharides and other plant glycans, including the hemicellulose xyloglucan, pectic rhamnogalacturonan-I (RG-I) and rhamnogalacturonan-II (RG-II), arabinogalactan proteins, and N-linked glycans 147:381 The monosaccharide L-fucose (L-Fuc) is a common component of plant cell wall polysaccharides and other plant glycans, including the hemicellulose xyloglucan, pectic rhamnogalacturonan-I (RG-I) and rhamnogalacturonan-II (RG-II), arabinogalactan proteins, and N-linked glycans. 26414071 1 37 theme monosaccharide 112:125 arg1 L-Fuc 137:141 L-Fuc 137:141 L-Fuc 137:141 The monosaccharide L-fucose (L-Fuc) is a common component of plant cell wall polysaccharides and other plant glycans, including the hemicellulose xyloglucan, pectic rhamnogalacturonan-I (RG-I) and rhamnogalacturonan-II (RG-II), arabinogalactan proteins, and N-linked glycans. 26414071 1 37 theme monosaccharide 112:125 arg1 L-fucose 127:134 The monosaccharide L-fucose 108:134 The monosaccharide L-fucose (L-Fuc) 108:142 The monosaccharide L-fucose (L-Fuc) is a common component of plant cell wall polysaccharides and other plant glycans, including the hemicellulose xyloglucan, pectic rhamnogalacturonan-I (RG-I) and rhamnogalacturonan-II (RG-II), arabinogalactan proteins, and N-linked glycans. 26414071 2 38 theme cell 438:441 arg1 polysaccharides 448:462 many plant cell wall polysaccharides 427:462 many plant cell wall polysaccharides 427:462 Mutations compromising the biosynthesis of many plant cell wall polysaccharides are lethal, and as a result, small molecule inhibitors of plant cell wall polysaccharide biosynthesis have been developed because these molecules can be applied at defined concentrations and developmental stages. 26414071 2 39 theme wall 443:446 arg1 polysaccharides 448:462 many plant cell wall polysaccharides 427:462 many plant cell wall polysaccharides 427:462 Mutations compromising the biosynthesis of many plant cell wall polysaccharides are lethal, and as a result, small molecule inhibitors of plant cell wall polysaccharide biosynthesis have been developed because these molecules can be applied at defined concentrations and developmental stages. 26414071 5 40 theme inhibitory 1175:1184 arg1 GDP-2F-Fuc 1136:1145 the sugar nucleotide GDP-2F-Fuc 1115:1145 the sugar nucleotide GDP-2F-Fuc 1115:1145 These phenotypic defects were dependent upon the L-Fuc salvage pathway enzyme L-Fucose Kinase/ GDP-L-Fucose Pyrophosphorylase (FKGP), suggesting that 2F-Fuc is metabolically converted to the sugar nucleotide GDP-2F-Fuc, which serves as the active inhibitory molecule. 26414071 5 40 theme inhibitory 1175:1184 arg1 molecule 1186:1193 the active inhibitory molecule 1164:1193 the active inhibitory molecule 1164:1193 These phenotypic defects were dependent upon the L-Fuc salvage pathway enzyme L-Fucose Kinase/ GDP-L-Fucose Pyrophosphorylase (FKGP), suggesting that 2F-Fuc is metabolically converted to the sugar nucleotide GDP-2F-Fuc, which serves as the active inhibitory molecule. 26414071 2 41 theme biosynthesis 553:564 arg1 result 485:490 a result 483:490 a result 483:490 Mutations compromising the biosynthesis of many plant cell wall polysaccharides are lethal, and as a result, small molecule inhibitors of plant cell wall polysaccharide biosynthesis have been developed because these molecules can be applied at defined concentrations and developmental stages. 26414071 2 41 theme biosynthesis 553:564 arg1 inhibitors 508:517 small molecule inhibitors 493:517 small molecule inhibitors of plant cell wall polysaccharide biosynthesis 493:564 Mutations compromising the biosynthesis of many plant cell wall polysaccharides are lethal, and as a result, small molecule inhibitors of plant cell wall polysaccharide biosynthesis have been developed because these molecules can be applied at defined concentrations and developmental stages. 26414071 5 42 theme sugar 1119:1123 arg1 molecule 1186:1193 the active inhibitory molecule 1164:1193 the active inhibitory molecule 1164:1193 These phenotypic defects were dependent upon the L-Fuc salvage pathway enzyme L-Fucose Kinase/ GDP-L-Fucose Pyrophosphorylase (FKGP), suggesting that 2F-Fuc is metabolically converted to the sugar nucleotide GDP-2F-Fuc, which serves as the active inhibitory molecule. 26414071 5 42 theme sugar 1119:1123 arg1 GDP-2F-Fuc 1136:1145 the sugar nucleotide GDP-2F-Fuc 1115:1145 the sugar nucleotide GDP-2F-Fuc 1115:1145 These phenotypic defects were dependent upon the L-Fuc salvage pathway enzyme L-Fucose Kinase/ GDP-L-Fucose Pyrophosphorylase (FKGP), suggesting that 2F-Fuc is metabolically converted to the sugar nucleotide GDP-2F-Fuc, which serves as the active inhibitory molecule. 26414071 5 43 theme enzyme 999:1004 arg1 FKGP 1055:1058 FKGP 1055:1058 FKGP 1055:1058 These phenotypic defects were dependent upon the L-Fuc salvage pathway enzyme L-Fucose Kinase/ GDP-L-Fucose Pyrophosphorylase (FKGP), suggesting that 2F-Fuc is metabolically converted to the sugar nucleotide GDP-2F-Fuc, which serves as the active inhibitory molecule. 26414071 5 43 theme enzyme 999:1004 arg1 Pyrophosphorylase 1036:1052 the L-Fuc salvage pathway enzyme L-Fucose Kinase/ GDP-L-Fucose Pyrophosphorylase 973:1052 the L-Fuc salvage pathway enzyme L-Fucose Kinase/ GDP-L-Fucose Pyrophosphorylase (FKGP) 973:1059 These phenotypic defects were dependent upon the L-Fuc salvage pathway enzyme L-Fucose Kinase/ GDP-L-Fucose Pyrophosphorylase (FKGP), suggesting that 2F-Fuc is metabolically converted to the sugar nucleotide GDP-2F-Fuc, which serves as the active inhibitory molecule. 26414071 8 44 theme polysaccharide 1844:1857 arg1 biosynthesis 1859:1870 cell wall polysaccharide biosynthesis 1834:1870 cell wall polysaccharide biosynthesis 1834:1870 Overall, the results presented here suggest that 2F-Fuc is a metabolically incorporated inhibitor of plant cellular fucosylation events, and potentially suggest that other 2-fluorinated monosaccharides could serve as useful chemical probes for the inhibition of cell wall polysaccharide biosynthesis. 26414071 1 45 theme other 205:209 arg1 glycans 217:223 other plant glycans 205:223 other plant glycans 205:223 The monosaccharide L-fucose (L-Fuc) is a common component of plant cell wall polysaccharides and other plant glycans, including the hemicellulose xyloglucan, pectic rhamnogalacturonan-I (RG-I) and rhamnogalacturonan-II (RG-II), arabinogalactan proteins, and N-linked glycans. 26414071 2 46 theme polysaccharide 538:551 arg1 biosynthesis 553:564 plant cell wall polysaccharide biosynthesis 522:564 plant cell wall polysaccharide biosynthesis 522:564 Mutations compromising the biosynthesis of many plant cell wall polysaccharides are lethal, and as a result, small molecule inhibitors of plant cell wall polysaccharide biosynthesis have been developed because these molecules can be applied at defined concentrations and developmental stages. 26414071 2 47 theme many 427:430 arg1 polysaccharides 448:462 many plant cell wall polysaccharides 427:462 many plant cell wall polysaccharides 427:462 Mutations compromising the biosynthesis of many plant cell wall polysaccharides are lethal, and as a result, small molecule inhibitors of plant cell wall polysaccharide biosynthesis have been developed because these molecules can be applied at defined concentrations and developmental stages. 26414071 4 48 theme Arabidopsis 846:856 arg1 growth 892:897 reduced root growth 879:897 reduced root growth 879:897 2-fluoro-L-fucose (2F-Fuc) analogs caused severe growth phenotypes when applied to Arabidopsis seedlings, including reduced root growth and altered root morphology. 26414071 4 48 theme Arabidopsis 846:856 arg1 seedlings 858:866 Arabidopsis seedlings 846:866 Arabidopsis seedlings 846:866 2-fluoro-L-fucose (2F-Fuc) analogs caused severe growth phenotypes when applied to Arabidopsis seedlings, including reduced root growth and altered root morphology. 26414071 4 48 theme Arabidopsis 846:856 arg1 morphology 916:925 altered root morphology 903:925 altered root morphology 903:925 2-fluoro-L-fucose (2F-Fuc) analogs caused severe growth phenotypes when applied to Arabidopsis seedlings, including reduced root growth and altered root morphology. 26414071 8 49 theme plant 1673:1677 arg1 events 1701:1706 plant cellular fucosylation events 1673:1706 plant cellular fucosylation events 1673:1706 Overall, the results presented here suggest that 2F-Fuc is a metabolically incorporated inhibitor of plant cellular fucosylation events, and potentially suggest that other 2-fluorinated monosaccharides could serve as useful chemical probes for the inhibition of cell wall polysaccharide biosynthesis. 26414071 1 50 theme plant 211:215 arg1 glycans 217:223 other plant glycans 205:223 other plant glycans 205:223 The monosaccharide L-fucose (L-Fuc) is a common component of plant cell wall polysaccharides and other plant glycans, including the hemicellulose xyloglucan, pectic rhamnogalacturonan-I (RG-I) and rhamnogalacturonan-II (RG-II), arabinogalactan proteins, and N-linked glycans. 26414071 0 51 theme Incorporated 37:48 arg1 Inhibitor 50:58 a Metabolically Incorporated Inhibitor 21:58 a Metabolically Incorporated Inhibitor of Plant Cell Wall Polysaccharide Fucosylation 21:105 2-Fluoro-L-Fucose Is a Metabolically Incorporated Inhibitor of Plant Cell Wall Polysaccharide Fucosylation. 26414071 0 51 theme Incorporated 37:48 arg1 2-Fluoro-L-Fucose 0:16 2-Fluoro-L-Fucose 0:16 2-Fluoro-L-Fucose 0:16 2-Fluoro-L-Fucose Is a Metabolically Incorporated Inhibitor of Plant Cell Wall Polysaccharide Fucosylation. 26414071 2 52 theme wall 533:536 arg1 biosynthesis 553:564 plant cell wall polysaccharide biosynthesis 522:564 plant cell wall polysaccharide biosynthesis 522:564 Mutations compromising the biosynthesis of many plant cell wall polysaccharides are lethal, and as a result, small molecule inhibitors of plant cell wall polysaccharide biosynthesis have been developed because these molecules can be applied at defined concentrations and developmental stages. 26414071 1 53 theme glycans 217:223 arg1 component 156:164 a common component 147:164 a common component of plant cell wall polysaccharides and other plant glycans, including the hemicellulose xyloglucan, pectic rhamnogalacturonan-I (RG-I) and rhamnogalacturonan-II (RG-II), arabinogalactan proteins, and N-linked glycans 147:381 The monosaccharide L-fucose (L-Fuc) is a common component of plant cell wall polysaccharides and other plant glycans, including the hemicellulose xyloglucan, pectic rhamnogalacturonan-I (RG-I) and rhamnogalacturonan-II (RG-II), arabinogalactan proteins, and N-linked glycans. 26414071 1 53 theme glycans 217:223 arg1 L-fucose 127:134 The monosaccharide L-fucose 108:134 The monosaccharide L-fucose (L-Fuc) 108:142 The monosaccharide L-fucose (L-Fuc) is a common component of plant cell wall polysaccharides and other plant glycans, including the hemicellulose xyloglucan, pectic rhamnogalacturonan-I (RG-I) and rhamnogalacturonan-II (RG-II), arabinogalactan proteins, and N-linked glycans. 26414071 0 54 theme Plant 63:67 arg1 Fucosylation 94:105 Plant Cell Wall Polysaccharide Fucosylation 63:105 Plant Cell Wall Polysaccharide Fucosylation 63:105 2-Fluoro-L-Fucose Is a Metabolically Incorporated Inhibitor of Plant Cell Wall Polysaccharide Fucosylation. 26414071 8 55 theme incorporated 1647:1658 arg1 inhibitor 1660:1668 a metabolically incorporated inhibitor 1631:1668 a metabolically incorporated inhibitor of plant cellular fucosylation events 1631:1706 Overall, the results presented here suggest that 2F-Fuc is a metabolically incorporated inhibitor of plant cellular fucosylation events, and potentially suggest that other 2-fluorinated monosaccharides could serve as useful chemical probes for the inhibition of cell wall polysaccharide biosynthesis. 26414071 8 55 theme incorporated 1647:1658 arg1 2F-Fuc 1621:1626 2F-Fuc 1621:1626 2F-Fuc 1621:1626 Overall, the results presented here suggest that 2F-Fuc is a metabolically incorporated inhibitor of plant cellular fucosylation events, and potentially suggest that other 2-fluorinated monosaccharides could serve as useful chemical probes for the inhibition of cell wall polysaccharide biosynthesis. 26414071 8 56 theme wall 1839:1842 arg1 biosynthesis 1859:1870 cell wall polysaccharide biosynthesis 1834:1870 cell wall polysaccharide biosynthesis 1834:1870 Overall, the results presented here suggest that 2F-Fuc is a metabolically incorporated inhibitor of plant cellular fucosylation events, and potentially suggest that other 2-fluorinated monosaccharides could serve as useful chemical probes for the inhibition of cell wall polysaccharide biosynthesis. 26414071 2 57 theme small 493:497 arg1 result 485:490 a result 483:490 a result 483:490 Mutations compromising the biosynthesis of many plant cell wall polysaccharides are lethal, and as a result, small molecule inhibitors of plant cell wall polysaccharide biosynthesis have been developed because these molecules can be applied at defined concentrations and developmental stages. 26414071 2 57 theme small 493:497 arg1 inhibitors 508:517 small molecule inhibitors 493:517 small molecule inhibitors of plant cell wall polysaccharide biosynthesis 493:564 Mutations compromising the biosynthesis of many plant cell wall polysaccharides are lethal, and as a result, small molecule inhibitors of plant cell wall polysaccharide biosynthesis have been developed because these molecules can be applied at defined concentrations and developmental stages. 26414071 8 58 theme biosynthesis 1859:1870 arg1 inhibition 1820:1829 the inhibition 1816:1829 the inhibition of cell wall polysaccharide biosynthesis 1816:1870 Overall, the results presented here suggest that 2F-Fuc is a metabolically incorporated inhibitor of plant cellular fucosylation events, and potentially suggest that other 2-fluorinated monosaccharides could serve as useful chemical probes for the inhibition of cell wall polysaccharide biosynthesis. 26414071 7 59 theme RG-II 1552:1556 arg1 biosynthesis 1558:1569 RG-II biosynthesis 1552:1569 RG-II biosynthesis 1552:1569 Additionally, phenotypic defects induced by 2F-Fuc treatment could be partially relieved by the exogenous application of boric acid, suggesting that 2F-Fuc inhibits RG-II biosynthesis. 26414071 6 60 theme matrix 1227:1232 arg1 polysaccharides 1234:1248 cell wall matrix polysaccharides 1217:1248 cell wall matrix polysaccharides 1217:1248 The L-Fuc content of cell wall matrix polysaccharides was reduced in plants treated with 2F-Fuc, suggesting that this molecule inhibits the incorporation of L-Fuc into these polysaccharides. 26414071 5 61 theme active 1168:1173 arg1 GDP-2F-Fuc 1136:1145 the sugar nucleotide GDP-2F-Fuc 1115:1145 the sugar nucleotide GDP-2F-Fuc 1115:1145 These phenotypic defects were dependent upon the L-Fuc salvage pathway enzyme L-Fucose Kinase/ GDP-L-Fucose Pyrophosphorylase (FKGP), suggesting that 2F-Fuc is metabolically converted to the sugar nucleotide GDP-2F-Fuc, which serves as the active inhibitory molecule. 26414071 5 61 theme active 1168:1173 arg1 molecule 1186:1193 the active inhibitory molecule 1164:1193 the active inhibitory molecule 1164:1193 These phenotypic defects were dependent upon the L-Fuc salvage pathway enzyme L-Fucose Kinase/ GDP-L-Fucose Pyrophosphorylase (FKGP), suggesting that 2F-Fuc is metabolically converted to the sugar nucleotide GDP-2F-Fuc, which serves as the active inhibitory molecule. 26414071 6 62 theme L-Fuc 1200:1204 arg1 content 1206:1212 The L-Fuc content 1196:1212 The L-Fuc content of cell wall matrix polysaccharides 1196:1248 The L-Fuc content of cell wall matrix polysaccharides was reduced in plants treated with 2F-Fuc, suggesting that this molecule inhibits the incorporation of L-Fuc into these polysaccharides. 26414071 7 63 theme phenotypic 1401:1410 arg1 defects 1412:1418 phenotypic defects 1401:1418 phenotypic defects induced by 2F-Fuc treatment 1401:1446 Additionally, phenotypic defects induced by 2F-Fuc treatment could be partially relieved by the exogenous application of boric acid, suggesting that 2F-Fuc inhibits RG-II biosynthesis. 26414071 8 64 theme fucosylation 1688:1699 arg1 events 1701:1706 plant cellular fucosylation events 1673:1706 plant cellular fucosylation events 1673:1706 Overall, the results presented here suggest that 2F-Fuc is a metabolically incorporated inhibitor of plant cellular fucosylation events, and potentially suggest that other 2-fluorinated monosaccharides could serve as useful chemical probes for the inhibition of cell wall polysaccharide biosynthesis. 26414071 8 65 theme 2-fluorinated 1744:1756 arg1 monosaccharides 1758:1772 other 2-fluorinated monosaccharides 1738:1772 other 2-fluorinated monosaccharides 1738:1772 Overall, the results presented here suggest that 2F-Fuc is a metabolically incorporated inhibitor of plant cellular fucosylation events, and potentially suggest that other 2-fluorinated monosaccharides could serve as useful chemical probes for the inhibition of cell wall polysaccharide biosynthesis. 26414071 8 65 theme 2-fluorinated 1744:1756 arg1 probes 1805:1810 useful chemical probes 1789:1810 useful chemical probes for the inhibition of cell wall polysaccharide biosynthesis 1789:1870 Overall, the results presented here suggest that 2F-Fuc is a metabolically incorporated inhibitor of plant cellular fucosylation events, and potentially suggest that other 2-fluorinated monosaccharides could serve as useful chemical probes for the inhibition of cell wall polysaccharide biosynthesis. 26414071 3 66 theme fucosylation 749:760 arg1 inhibitors 729:738 novel small molecule inhibitors 708:738 novel small molecule inhibitors of plant fucosylation 708:760 In this study, we characterize novel small molecule inhibitors of plant fucosylation. 26414071 5 67 theme pathway 991:997 arg1 FKGP 1055:1058 FKGP 1055:1058 FKGP 1055:1058 These phenotypic defects were dependent upon the L-Fuc salvage pathway enzyme L-Fucose Kinase/ GDP-L-Fucose Pyrophosphorylase (FKGP), suggesting that 2F-Fuc is metabolically converted to the sugar nucleotide GDP-2F-Fuc, which serves as the active inhibitory molecule. 26414071 5 67 theme pathway 991:997 arg1 Pyrophosphorylase 1036:1052 the L-Fuc salvage pathway enzyme L-Fucose Kinase/ GDP-L-Fucose Pyrophosphorylase 973:1052 the L-Fuc salvage pathway enzyme L-Fucose Kinase/ GDP-L-Fucose Pyrophosphorylase (FKGP) 973:1059 These phenotypic defects were dependent upon the L-Fuc salvage pathway enzyme L-Fucose Kinase/ GDP-L-Fucose Pyrophosphorylase (FKGP), suggesting that 2F-Fuc is metabolically converted to the sugar nucleotide GDP-2F-Fuc, which serves as the active inhibitory molecule. 26414071 6 68 theme polysaccharides 1234:1248 arg1 content 1206:1212 The L-Fuc content 1196:1212 The L-Fuc content of cell wall matrix polysaccharides 1196:1248 The L-Fuc content of cell wall matrix polysaccharides was reduced in plants treated with 2F-Fuc, suggesting that this molecule inhibits the incorporation of L-Fuc into these polysaccharides. 26414071 6 69 theme cell 1217:1220 arg1 polysaccharides 1234:1248 cell wall matrix polysaccharides 1217:1248 cell wall matrix polysaccharides 1217:1248 The L-Fuc content of cell wall matrix polysaccharides was reduced in plants treated with 2F-Fuc, suggesting that this molecule inhibits the incorporation of L-Fuc into these polysaccharides. 26414071 4 70 theme growth 812:817 arg1 phenotypes 819:828 severe growth phenotypes 805:828 severe growth phenotypes 805:828 2-fluoro-L-fucose (2F-Fuc) analogs caused severe growth phenotypes when applied to Arabidopsis seedlings, including reduced root growth and altered root morphology. 26414071 5 71 theme nucleotide 1125:1134 arg1 molecule 1186:1193 the active inhibitory molecule 1164:1193 the active inhibitory molecule 1164:1193 These phenotypic defects were dependent upon the L-Fuc salvage pathway enzyme L-Fucose Kinase/ GDP-L-Fucose Pyrophosphorylase (FKGP), suggesting that 2F-Fuc is metabolically converted to the sugar nucleotide GDP-2F-Fuc, which serves as the active inhibitory molecule. 26414071 5 71 theme nucleotide 1125:1134 arg1 GDP-2F-Fuc 1136:1145 the sugar nucleotide GDP-2F-Fuc 1115:1145 the sugar nucleotide GDP-2F-Fuc 1115:1145 These phenotypic defects were dependent upon the L-Fuc salvage pathway enzyme L-Fucose Kinase/ GDP-L-Fucose Pyrophosphorylase (FKGP), suggesting that 2F-Fuc is metabolically converted to the sugar nucleotide GDP-2F-Fuc, which serves as the active inhibitory molecule. 26414071 8 72 theme cellular 1679:1686 arg1 events 1701:1706 plant cellular fucosylation events 1673:1706 plant cellular fucosylation events 1673:1706 Overall, the results presented here suggest that 2F-Fuc is a metabolically incorporated inhibitor of plant cellular fucosylation events, and potentially suggest that other 2-fluorinated monosaccharides could serve as useful chemical probes for the inhibition of cell wall polysaccharide biosynthesis. 26414071 0 73 theme Wall 74:77 arg1 Fucosylation 94:105 Plant Cell Wall Polysaccharide Fucosylation 63:105 Plant Cell Wall Polysaccharide Fucosylation 63:105 2-Fluoro-L-Fucose Is a Metabolically Incorporated Inhibitor of Plant Cell Wall Polysaccharide Fucosylation. 26414071 5 74 theme GDP-L-Fucose 1023:1034 arg1 FKGP 1055:1058 FKGP 1055:1058 FKGP 1055:1058 These phenotypic defects were dependent upon the L-Fuc salvage pathway enzyme L-Fucose Kinase/ GDP-L-Fucose Pyrophosphorylase (FKGP), suggesting that 2F-Fuc is metabolically converted to the sugar nucleotide GDP-2F-Fuc, which serves as the active inhibitory molecule. 26414071 5 74 theme GDP-L-Fucose 1023:1034 arg1 Pyrophosphorylase 1036:1052 the L-Fuc salvage pathway enzyme L-Fucose Kinase/ GDP-L-Fucose Pyrophosphorylase 973:1052 the L-Fuc salvage pathway enzyme L-Fucose Kinase/ GDP-L-Fucose Pyrophosphorylase (FKGP) 973:1059 These phenotypic defects were dependent upon the L-Fuc salvage pathway enzyme L-Fucose Kinase/ GDP-L-Fucose Pyrophosphorylase (FKGP), suggesting that 2F-Fuc is metabolically converted to the sugar nucleotide GDP-2F-Fuc, which serves as the active inhibitory molecule. 26414071 6 75 theme wall 1222:1225 arg1 polysaccharides 1234:1248 cell wall matrix polysaccharides 1217:1248 cell wall matrix polysaccharides 1217:1248 The L-Fuc content of cell wall matrix polysaccharides was reduced in plants treated with 2F-Fuc, suggesting that this molecule inhibits the incorporation of L-Fuc into these polysaccharides. 26414071 8 76 theme useful 1789:1794 arg1 monosaccharides 1758:1772 other 2-fluorinated monosaccharides 1738:1772 other 2-fluorinated monosaccharides 1738:1772 Overall, the results presented here suggest that 2F-Fuc is a metabolically incorporated inhibitor of plant cellular fucosylation events, and potentially suggest that other 2-fluorinated monosaccharides could serve as useful chemical probes for the inhibition of cell wall polysaccharide biosynthesis. 26414071 8 76 theme useful 1789:1794 arg1 probes 1805:1810 useful chemical probes 1789:1810 useful chemical probes for the inhibition of cell wall polysaccharide biosynthesis 1789:1870 Overall, the results presented here suggest that 2F-Fuc is a metabolically incorporated inhibitor of plant cellular fucosylation events, and potentially suggest that other 2-fluorinated monosaccharides could serve as useful chemical probes for the inhibition of cell wall polysaccharide biosynthesis. 26414071 0 77 theme Cell 69:72 arg1 Fucosylation 94:105 Plant Cell Wall Polysaccharide Fucosylation 63:105 Plant Cell Wall Polysaccharide Fucosylation 63:105 2-Fluoro-L-Fucose Is a Metabolically Incorporated Inhibitor of Plant Cell Wall Polysaccharide Fucosylation. 26414071 3 78 theme small 714:718 arg1 inhibitors 729:738 novel small molecule inhibitors 708:738 novel small molecule inhibitors of plant fucosylation 708:760 In this study, we characterize novel small molecule inhibitors of plant fucosylation. 26414071 8 79 theme cell 1834:1837 arg1 biosynthesis 1859:1870 cell wall polysaccharide biosynthesis 1834:1870 cell wall polysaccharide biosynthesis 1834:1870 Overall, the results presented here suggest that 2F-Fuc is a metabolically incorporated inhibitor of plant cellular fucosylation events, and potentially suggest that other 2-fluorinated monosaccharides could serve as useful chemical probes for the inhibition of cell wall polysaccharide biosynthesis. 26414071 3 80 theme molecule 720:727 arg1 inhibitors 729:738 novel small molecule inhibitors 708:738 novel small molecule inhibitors of plant fucosylation 708:760 In this study, we characterize novel small molecule inhibitors of plant fucosylation. 26414071 1 81 theme common 149:154 arg1 component 156:164 a common component 147:164 a common component of plant cell wall polysaccharides and other plant glycans, including the hemicellulose xyloglucan, pectic rhamnogalacturonan-I (RG-I) and rhamnogalacturonan-II (RG-II), arabinogalactan proteins, and N-linked glycans 147:381 The monosaccharide L-fucose (L-Fuc) is a common component of plant cell wall polysaccharides and other plant glycans, including the hemicellulose xyloglucan, pectic rhamnogalacturonan-I (RG-I) and rhamnogalacturonan-II (RG-II), arabinogalactan proteins, and N-linked glycans. 26414071 1 81 theme common 149:154 arg1 L-fucose 127:134 The monosaccharide L-fucose 108:134 The monosaccharide L-fucose (L-Fuc) 108:142 The monosaccharide L-fucose (L-Fuc) is a common component of plant cell wall polysaccharides and other plant glycans, including the hemicellulose xyloglucan, pectic rhamnogalacturonan-I (RG-I) and rhamnogalacturonan-II (RG-II), arabinogalactan proteins, and N-linked glycans. 26414071 8 82 theme events 1701:1706 arg1 inhibitor 1660:1668 a metabolically incorporated inhibitor 1631:1668 a metabolically incorporated inhibitor of plant cellular fucosylation events 1631:1706 Overall, the results presented here suggest that 2F-Fuc is a metabolically incorporated inhibitor of plant cellular fucosylation events, and potentially suggest that other 2-fluorinated monosaccharides could serve as useful chemical probes for the inhibition of cell wall polysaccharide biosynthesis. 26414071 8 82 theme events 1701:1706 arg1 2F-Fuc 1621:1626 2F-Fuc 1621:1626 2F-Fuc 1621:1626 Overall, the results presented here suggest that 2F-Fuc is a metabolically incorporated inhibitor of plant cellular fucosylation events, and potentially suggest that other 2-fluorinated monosaccharides could serve as useful chemical probes for the inhibition of cell wall polysaccharide biosynthesis. 26414071 1 83 theme hemicellulose 240:252 arg1 xyloglucan 254:263 the hemicellulose xyloglucan 236:263 the hemicellulose xyloglucan 236:263 The monosaccharide L-fucose (L-Fuc) is a common component of plant cell wall polysaccharides and other plant glycans, including the hemicellulose xyloglucan, pectic rhamnogalacturonan-I (RG-I) and rhamnogalacturonan-II (RG-II), arabinogalactan proteins, and N-linked glycans. 25939548 4 0 attach present 698:704 arg1 study 689:693 this study 684:693 this study 684:693 In this study we present a newly engineered P. pastoris strain with improved protein production. 25939548 4 0 attach present 698:704 arg2 we 695:696 we 695:696 we 695:696 In this study we present a newly engineered P. pastoris strain with improved protein production. 25939548 7 1 theme inactive 1122:1129 arg1 form 1131:1134 An inactive form 1119:1134 An inactive form of the enzyme 1119:1148 An inactive form of the enzyme was produced by the bacterium, but the recombinant esterase from both yeasts was active even after its enzymatic deglycosylation, suggesting that the presence of N-linked carbohydrates in the mature protein is not essential for enzyme activity. 25939548 8 2 theme choice 1521:1526 arg1 importance 1503:1512 the importance 1499:1512 the importance of the choice of the heterologous host for successful production of soluble and active recombinant protein 1499:1619 Although the yield in S. cerevisiae was lower than that obtained in P. pastoris, this work demonstrates the importance of the choice of the heterologous host for successful production of soluble and active recombinant protein. 25939548 2 3 theme recombinant 350:360 arg1 protein 362:368 the recombinant protein 346:368 the recombinant protein 346:368 This enzyme produces aggregates in aqueous solutions, but the recombinant protein, expressed in Komagataella (synonym Pichia) pastoris, showed higher catalytic efficiency because of its higher solubility. 25939548 9 4 theme biocatalyst 1726:1736 arg1 properties 1707:1716 the properties 1703:1716 the properties of this biocatalyst 1703:1736 In addition, S. cerevisiae constitutes a good engineering platform for improving the properties of this biocatalyst. 25939548 2 5 theme higher 474:479 arg1 solubility 481:490 its higher solubility 470:490 its higher solubility 470:490 This enzyme produces aggregates in aqueous solutions, but the recombinant protein, expressed in Komagataella (synonym Pichia) pastoris, showed higher catalytic efficiency because of its higher solubility. 25939548 0 6 from expression 13:22 arg1 hosts 72:76 different hosts 62:76 different hosts 62:76 Heterologous expression of a fungal sterol esterase/lipase in different hosts: Effect on solubility, glycosylation and production. 25939548 1 7 theme versatile 160:168 arg1 OPE 187:189 OPE 187:189 OPE 187:189 Ophiostoma piceae secretes a versatile sterol-esterase (OPE) that shows high efficiency in both hydrolysis and synthesis of triglycerides and sterol esters. 25939548 1 7 theme versatile 160:168 arg1 sterol-esterase 170:184 a versatile sterol-esterase 158:184 a versatile sterol-esterase (OPE) that shows high efficiency in both hydrolysis and synthesis of triglycerides and sterol esters 158:285 Ophiostoma piceae secretes a versatile sterol-esterase (OPE) that shows high efficiency in both hydrolysis and synthesis of triglycerides and sterol esters. 25939548 7 8 attach presence 1300:1307 arg1 protein 1349:1355 the mature protein 1338:1355 the mature protein 1338:1355 An inactive form of the enzyme was produced by the bacterium, but the recombinant esterase from both yeasts was active even after its enzymatic deglycosylation, suggesting that the presence of N-linked carbohydrates in the mature protein is not essential for enzyme activity. 25939548 7 8 attach presence 1300:1307 arg2 carbohydrates 1321:1333 N-linked carbohydrates 1312:1333 N-linked carbohydrates 1312:1333 An inactive form of the enzyme was produced by the bacterium, but the recombinant esterase from both yeasts was active even after its enzymatic deglycosylation, suggesting that the presence of N-linked carbohydrates in the mature protein is not essential for enzyme activity. 25939548 4 9 theme protein 758:764 arg1 production 766:775 improved protein production 749:775 improved protein production 749:775 In this study we present a newly engineered P. pastoris strain with improved protein production. 25939548 6 10 theme P. pastoris 1036:1046 arg1 strain 1048:1053 the new P. pastoris strain 1028:1053 the new P. pastoris strain 1028:1053 The OPE produced in the new P. pastoris strain presented the same physicochemical properties than the old one. 25939548 1 11 theme triglycerides 255:267 arg1 efficiency 208:217 high efficiency 203:217 high efficiency in both hydrolysis and synthesis of triglycerides and sterol esters 203:285 Ophiostoma piceae secretes a versatile sterol-esterase (OPE) that shows high efficiency in both hydrolysis and synthesis of triglycerides and sterol esters. 25939548 7 12 theme recombinant 1189:1199 arg1 active 1231:1236 active 1231:1236 active 1231:1236 An inactive form of the enzyme was produced by the bacterium, but the recombinant esterase from both yeasts was active even after its enzymatic deglycosylation, suggesting that the presence of N-linked carbohydrates in the mature protein is not essential for enzyme activity. 25939548 7 12 theme recombinant 1189:1199 arg1 esterase 1201:1208 the recombinant esterase 1185:1208 the recombinant esterase from both yeasts 1185:1225 An inactive form of the enzyme was produced by the bacterium, but the recombinant esterase from both yeasts was active even after its enzymatic deglycosylation, suggesting that the presence of N-linked carbohydrates in the mature protein is not essential for enzyme activity. 25939548 4 13 theme improved 749:756 arg1 production 766:775 improved protein production 749:775 improved protein production 749:775 In this study we present a newly engineered P. pastoris strain with improved protein production. 25939548 7 14 theme enzyme 1143:1148 arg1 form 1131:1134 An inactive form 1119:1134 An inactive form of the enzyme 1119:1148 An inactive form of the enzyme was produced by the bacterium, but the recombinant esterase from both yeasts was active even after its enzymatic deglycosylation, suggesting that the presence of N-linked carbohydrates in the mature protein is not essential for enzyme activity. 25939548 3 15 theme N-terminal 533:542 arg1 sequence 544:551 the N-terminal sequence 529:551 the N-terminal sequence of the protein expressed in Pichia pastoris, which incorporated 4-8 additional amino acids 529:642 This fact owes to a modification in the N-terminal sequence of the protein expressed in Pichia pastoris, which incorporated 4-8 additional amino acids, affecting its aggregation behavior. 25939548 2 16 theme aqueous 323:329 arg1 solutions 331:339 aqueous solutions 323:339 aqueous solutions 323:339 This enzyme produces aggregates in aqueous solutions, but the recombinant protein, expressed in Komagataella (synonym Pichia) pastoris, showed higher catalytic efficiency because of its higher solubility. 25939548 9 17 theme engineering 1668:1678 arg1 platform 1680:1687 a good engineering platform 1661:1687 a good engineering platform for improving the properties of this biocatalyst 1661:1736 In addition, S. cerevisiae constitutes a good engineering platform for improving the properties of this biocatalyst. 25939548 6 18 theme same 1069:1072 arg1 properties 1090:1099 the same physicochemical properties 1065:1099 the same physicochemical properties 1065:1099 The OPE produced in the new P. pastoris strain presented the same physicochemical properties than the old one. 25939548 7 19 theme carbohydrates 1321:1333 arg1 essential 1364:1372 essential 1364:1372 essential 1364:1372 An inactive form of the enzyme was produced by the bacterium, but the recombinant esterase from both yeasts was active even after its enzymatic deglycosylation, suggesting that the presence of N-linked carbohydrates in the mature protein is not essential for enzyme activity. 25939548 7 19 theme carbohydrates 1321:1333 arg1 presence 1300:1307 the presence 1296:1307 the presence of N-linked carbohydrates in the mature protein 1296:1355 An inactive form of the enzyme was produced by the bacterium, but the recombinant esterase from both yeasts was active even after its enzymatic deglycosylation, suggesting that the presence of N-linked carbohydrates in the mature protein is not essential for enzyme activity. 25939548 7 20 link N-linked 1312:1319 arg1 carbohydrates 1321:1333 N-linked carbohydrates 1312:1333 N-linked carbohydrates 1312:1333 An inactive form of the enzyme was produced by the bacterium, but the recombinant esterase from both yeasts was active even after its enzymatic deglycosylation, suggesting that the presence of N-linked carbohydrates in the mature protein is not essential for enzyme activity. 25939548 0 21 theme Heterologous 0:11 arg1 expression 13:22 Heterologous expression 0:22 Heterologous expression of a fungal sterol esterase/lipase in different hosts: Effect on solubility, glycosylation and production. 0:129 Heterologous expression of a fungal sterol esterase/lipase in different hosts: Effect on solubility, glycosylation and production. 25939548 2 22 theme Komagataella 384:395 arg1 pastoris 414:421 Komagataella (synonym Pichia) pastoris 384:421 Komagataella (synonym Pichia) pastoris 384:421 This enzyme produces aggregates in aqueous solutions, but the recombinant protein, expressed in Komagataella (synonym Pichia) pastoris, showed higher catalytic efficiency because of its higher solubility. 25939548 2 23 theme catalytic 438:446 arg1 efficiency 448:457 higher catalytic efficiency 431:457 higher catalytic efficiency 431:457 This enzyme produces aggregates in aqueous solutions, but the recombinant protein, expressed in Komagataella (synonym Pichia) pastoris, showed higher catalytic efficiency because of its higher solubility. 25939548 5 24 from protein 811:817 arg1 cerevisiae 846:855 the yeast Saccharomyces cerevisiae 822:855 the yeast Saccharomyces cerevisiae 822:855 We also produced the recombinant protein in the yeast Saccharomyces cerevisiae and in the prokaryotic host Escherichia coli, corroborating that the presence of these N-terminal extra amino acids affected the protein's solubility. 25939548 5 24 from protein 811:817 arg1 host 880:883 the prokaryotic host 864:883 the prokaryotic host Escherichia coli 864:900 We also produced the recombinant protein in the yeast Saccharomyces cerevisiae and in the prokaryotic host Escherichia coli, corroborating that the presence of these N-terminal extra amino acids affected the protein's solubility. 25939548 8 25 theme heterologous 1535:1546 arg1 host 1548:1551 the heterologous host 1531:1551 the heterologous host 1531:1551 Although the yield in S. cerevisiae was lower than that obtained in P. pastoris, this work demonstrates the importance of the choice of the heterologous host for successful production of soluble and active recombinant protein. 25939548 4 26 theme P. pastoris 725:735 arg1 strain 737:742 a newly engineered P. pastoris strain 706:742 a newly engineered P. pastoris strain with improved protein production 706:775 In this study we present a newly engineered P. pastoris strain with improved protein production. 25939548 7 27 theme enzymatic 1253:1261 arg1 deglycosylation 1263:1277 its enzymatic deglycosylation 1249:1277 its enzymatic deglycosylation 1249:1277 An inactive form of the enzyme was produced by the bacterium, but the recombinant esterase from both yeasts was active even after its enzymatic deglycosylation, suggesting that the presence of N-linked carbohydrates in the mature protein is not essential for enzyme activity. 25939548 5 28 theme prokaryotic 868:878 arg1 host 880:883 the prokaryotic host 864:883 the prokaryotic host Escherichia coli 864:900 We also produced the recombinant protein in the yeast Saccharomyces cerevisiae and in the prokaryotic host Escherichia coli, corroborating that the presence of these N-terminal extra amino acids affected the protein's solubility. 25939548 2 29 theme higher 431:436 arg1 efficiency 448:457 higher catalytic efficiency 431:457 higher catalytic efficiency 431:457 This enzyme produces aggregates in aqueous solutions, but the recombinant protein, expressed in Komagataella (synonym Pichia) pastoris, showed higher catalytic efficiency because of its higher solubility. 25939548 1 30 theme sterol 273:278 arg1 esters 280:285 sterol esters 273:285 sterol esters 273:285 Ophiostoma piceae secretes a versatile sterol-esterase (OPE) that shows high efficiency in both hydrolysis and synthesis of triglycerides and sterol esters. 25939548 7 31 from yeasts 1220:1225 arg1 active 1231:1236 active 1231:1236 active 1231:1236 An inactive form of the enzyme was produced by the bacterium, but the recombinant esterase from both yeasts was active even after its enzymatic deglycosylation, suggesting that the presence of N-linked carbohydrates in the mature protein is not essential for enzyme activity. 25939548 7 31 from yeasts 1220:1225 arg1 esterase 1201:1208 the recombinant esterase 1185:1208 the recombinant esterase from both yeasts 1185:1225 An inactive form of the enzyme was produced by the bacterium, but the recombinant esterase from both yeasts was active even after its enzymatic deglycosylation, suggesting that the presence of N-linked carbohydrates in the mature protein is not essential for enzyme activity. 25939548 3 32 theme protein 560:566 arg1 sequence 544:551 the N-terminal sequence 529:551 the N-terminal sequence of the protein expressed in Pichia pastoris, which incorporated 4-8 additional amino acids 529:642 This fact owes to a modification in the N-terminal sequence of the protein expressed in Pichia pastoris, which incorporated 4-8 additional amino acids, affecting its aggregation behavior. 25939548 7 33 theme N-linked 1312:1319 arg1 carbohydrates 1321:1333 N-linked carbohydrates 1312:1333 N-linked carbohydrates 1312:1333 An inactive form of the enzyme was produced by the bacterium, but the recombinant esterase from both yeasts was active even after its enzymatic deglycosylation, suggesting that the presence of N-linked carbohydrates in the mature protein is not essential for enzyme activity. 25939548 8 34 theme recombinant 1601:1611 arg1 protein 1613:1619 soluble and active recombinant protein 1582:1619 soluble and active recombinant protein 1582:1619 Although the yield in S. cerevisiae was lower than that obtained in P. pastoris, this work demonstrates the importance of the choice of the heterologous host for successful production of soluble and active recombinant protein. 25939548 1 35 theme esters 280:285 arg1 efficiency 208:217 high efficiency 203:217 high efficiency in both hydrolysis and synthesis of triglycerides and sterol esters 203:285 Ophiostoma piceae secretes a versatile sterol-esterase (OPE) that shows high efficiency in both hydrolysis and synthesis of triglycerides and sterol esters. 25939548 5 36 theme extra 955:959 arg1 acids 967:971 these N-terminal extra amino acids 938:971 these N-terminal extra amino acids 938:971 We also produced the recombinant protein in the yeast Saccharomyces cerevisiae and in the prokaryotic host Escherichia coli, corroborating that the presence of these N-terminal extra amino acids affected the protein's solubility. 25939548 5 37 theme yeast 826:830 arg1 cerevisiae 846:855 the yeast Saccharomyces cerevisiae 822:855 the yeast Saccharomyces cerevisiae 822:855 We also produced the recombinant protein in the yeast Saccharomyces cerevisiae and in the prokaryotic host Escherichia coli, corroborating that the presence of these N-terminal extra amino acids affected the protein's solubility. 25939548 4 38 theme engineered 714:723 arg1 strain 737:742 a newly engineered P. pastoris strain 706:742 a newly engineered P. pastoris strain with improved protein production 706:775 In this study we present a newly engineered P. pastoris strain with improved protein production. 25939548 5 39 theme N-terminal 944:953 arg1 acids 967:971 these N-terminal extra amino acids 938:971 these N-terminal extra amino acids 938:971 We also produced the recombinant protein in the yeast Saccharomyces cerevisiae and in the prokaryotic host Escherichia coli, corroborating that the presence of these N-terminal extra amino acids affected the protein's solubility. 25939548 0 40 from Effect 79:84 arg1 solubility 89:98 solubility 89:98 solubility 89:98 Heterologous expression of a fungal sterol esterase/lipase in different hosts: Effect on solubility, glycosylation and production. 25939548 0 40 from Effect 79:84 arg1 production 119:128 production 119:128 production 119:128 Heterologous expression of a fungal sterol esterase/lipase in different hosts: Effect on solubility, glycosylation and production. 25939548 0 40 from Effect 79:84 arg1 glycosylation 101:113 glycosylation 101:113 glycosylation 101:113 Heterologous expression of a fungal sterol esterase/lipase in different hosts: Effect on solubility, glycosylation and production. 25939548 5 41 theme amino 961:965 arg1 acids 967:971 these N-terminal extra amino acids 938:971 these N-terminal extra amino acids 938:971 We also produced the recombinant protein in the yeast Saccharomyces cerevisiae and in the prokaryotic host Escherichia coli, corroborating that the presence of these N-terminal extra amino acids affected the protein's solubility. 25939548 5 42 theme Saccharomyces 832:844 arg1 cerevisiae 846:855 the yeast Saccharomyces cerevisiae 822:855 the yeast Saccharomyces cerevisiae 822:855 We also produced the recombinant protein in the yeast Saccharomyces cerevisiae and in the prokaryotic host Escherichia coli, corroborating that the presence of these N-terminal extra amino acids affected the protein's solubility. 25939548 0 43 theme sterol 36:41 arg1 esterase/lipase 43:57 a fungal sterol esterase/lipase 27:57 a fungal sterol esterase/lipase 27:57 Heterologous expression of a fungal sterol esterase/lipase in different hosts: Effect on solubility, glycosylation and production. 25939548 8 44 theme host 1548:1551 arg1 choice 1521:1526 the choice 1517:1526 the choice of the heterologous host 1517:1551 Although the yield in S. cerevisiae was lower than that obtained in P. pastoris, this work demonstrates the importance of the choice of the heterologous host for successful production of soluble and active recombinant protein. 25939548 1 45 theme high 203:206 arg1 efficiency 208:217 high efficiency 203:217 high efficiency in both hydrolysis and synthesis of triglycerides and sterol esters 203:285 Ophiostoma piceae secretes a versatile sterol-esterase (OPE) that shows high efficiency in both hydrolysis and synthesis of triglycerides and sterol esters. 25939548 3 46 theme Pichia 581:586 arg1 pastoris 588:595 Pichia pastoris 581:595 Pichia pastoris 581:595 This fact owes to a modification in the N-terminal sequence of the protein expressed in Pichia pastoris, which incorporated 4-8 additional amino acids, affecting its aggregation behavior. 25939548 8 47 from yield 1408:1412 arg1 S. cerevisiae 1417:1429 S. cerevisiae 1417:1429 S. cerevisiae 1417:1429 Although the yield in S. cerevisiae was lower than that obtained in P. pastoris, this work demonstrates the importance of the choice of the heterologous host for successful production of soluble and active recombinant protein. 25939548 2 48 theme Pichia 406:411 arg1 pastoris 414:421 Komagataella (synonym Pichia) pastoris 384:421 Komagataella (synonym Pichia) pastoris 384:421 This enzyme produces aggregates in aqueous solutions, but the recombinant protein, expressed in Komagataella (synonym Pichia) pastoris, showed higher catalytic efficiency because of its higher solubility. 25939548 0 49 theme fungal 29:34 arg1 esterase/lipase 43:57 a fungal sterol esterase/lipase 27:57 a fungal sterol esterase/lipase 27:57 Heterologous expression of a fungal sterol esterase/lipase in different hosts: Effect on solubility, glycosylation and production. 25939548 3 50 theme additional 621:630 arg1 acids 638:642 4-8 additional amino acids 617:642 4-8 additional amino acids 617:642 This fact owes to a modification in the N-terminal sequence of the protein expressed in Pichia pastoris, which incorporated 4-8 additional amino acids, affecting its aggregation behavior. 25939548 7 51 theme enzyme 1378:1383 arg1 activity 1385:1392 enzyme activity 1378:1392 enzyme activity 1378:1392 An inactive form of the enzyme was produced by the bacterium, but the recombinant esterase from both yeasts was active even after its enzymatic deglycosylation, suggesting that the presence of N-linked carbohydrates in the mature protein is not essential for enzyme activity. 25939548 2 52 theme synonym 398:404 arg1 pastoris 414:421 Komagataella (synonym Pichia) pastoris 384:421 Komagataella (synonym Pichia) pastoris 384:421 This enzyme produces aggregates in aqueous solutions, but the recombinant protein, expressed in Komagataella (synonym Pichia) pastoris, showed higher catalytic efficiency because of its higher solubility. 25939548 4 53 with strain 737:742 arg1 production 766:775 improved protein production 749:775 improved protein production 749:775 In this study we present a newly engineered P. pastoris strain with improved protein production. 25939548 6 54 theme new 1032:1034 arg1 strain 1048:1053 the new P. pastoris strain 1028:1053 the new P. pastoris strain 1028:1053 The OPE produced in the new P. pastoris strain presented the same physicochemical properties than the old one. 25939548 3 55 theme amino 632:636 arg1 acids 638:642 4-8 additional amino acids 617:642 4-8 additional amino acids 617:642 This fact owes to a modification in the N-terminal sequence of the protein expressed in Pichia pastoris, which incorporated 4-8 additional amino acids, affecting its aggregation behavior. 25939548 1 56 from efficiency 208:217 arg1 hydrolysis 227:236 hydrolysis 227:236 hydrolysis 227:236 Ophiostoma piceae secretes a versatile sterol-esterase (OPE) that shows high efficiency in both hydrolysis and synthesis of triglycerides and sterol esters. 25939548 1 56 from efficiency 208:217 arg1 synthesis 242:250 synthesis 242:250 synthesis 242:250 Ophiostoma piceae secretes a versatile sterol-esterase (OPE) that shows high efficiency in both hydrolysis and synthesis of triglycerides and sterol esters. 25939548 0 57 theme esterase/lipase 43:57 arg1 expression 13:22 Heterologous expression 0:22 Heterologous expression of a fungal sterol esterase/lipase in different hosts: Effect on solubility, glycosylation and production. 0:129 Heterologous expression of a fungal sterol esterase/lipase in different hosts: Effect on solubility, glycosylation and production. 25939548 8 58 theme soluble 1582:1588 arg1 protein 1613:1619 soluble and active recombinant protein 1582:1619 soluble and active recombinant protein 1582:1619 Although the yield in S. cerevisiae was lower than that obtained in P. pastoris, this work demonstrates the importance of the choice of the heterologous host for successful production of soluble and active recombinant protein. 25939548 3 59 theme aggregation 659:669 arg1 behavior 671:678 its aggregation behavior 655:678 its aggregation behavior 655:678 This fact owes to a modification in the N-terminal sequence of the protein expressed in Pichia pastoris, which incorporated 4-8 additional amino acids, affecting its aggregation behavior. 25939548 9 60 theme good 1663:1666 arg1 platform 1680:1687 a good engineering platform 1661:1687 a good engineering platform for improving the properties of this biocatalyst 1661:1736 In addition, S. cerevisiae constitutes a good engineering platform for improving the properties of this biocatalyst. 25939548 7 61 from presence 1300:1307 arg1 protein 1349:1355 the mature protein 1338:1355 the mature protein 1338:1355 An inactive form of the enzyme was produced by the bacterium, but the recombinant esterase from both yeasts was active even after its enzymatic deglycosylation, suggesting that the presence of N-linked carbohydrates in the mature protein is not essential for enzyme activity. 25939548 5 62 dep Escherichia 885:895 arg1 coli 897:900 coli 897:900 coli 897:900 We also produced the recombinant protein in the yeast Saccharomyces cerevisiae and in the prokaryotic host Escherichia coli, corroborating that the presence of these N-terminal extra amino acids affected the protein's solubility. 25939548 8 63 theme active 1594:1599 arg1 protein 1613:1619 soluble and active recombinant protein 1582:1619 soluble and active recombinant protein 1582:1619 Although the yield in S. cerevisiae was lower than that obtained in P. pastoris, this work demonstrates the importance of the choice of the heterologous host for successful production of soluble and active recombinant protein. 25939548 5 64 theme acids 967:971 arg1 presence 926:933 the presence 922:933 the presence of these N-terminal extra amino acids 922:971 We also produced the recombinant protein in the yeast Saccharomyces cerevisiae and in the prokaryotic host Escherichia coli, corroborating that the presence of these N-terminal extra amino acids affected the protein's solubility. 25939548 1 65 theme Ophiostoma 131:140 arg1 piceae 142:147 Ophiostoma piceae 131:147 Ophiostoma piceae 131:147 Ophiostoma piceae secretes a versatile sterol-esterase (OPE) that shows high efficiency in both hydrolysis and synthesis of triglycerides and sterol esters. 25939548 6 66 theme old 1110:1112 arg1 one 1114:1116 the old one 1106:1116 the old one 1106:1116 The OPE produced in the new P. pastoris strain presented the same physicochemical properties than the old one. 25939548 0 67 dep expression 13:22 arg1 Effect 79:84 Effect 79:84 Heterologous expression of a fungal sterol esterase/lipase in different hosts: Effect on solubility, glycosylation and production. 0:129 Heterologous expression of a fungal sterol esterase/lipase in different hosts: Effect on solubility, glycosylation and production. 25939548 5 68 theme Escherichia 885:895 arg1 host 880:883 the prokaryotic host 864:883 the prokaryotic host Escherichia coli 864:900 We also produced the recombinant protein in the yeast Saccharomyces cerevisiae and in the prokaryotic host Escherichia coli, corroborating that the presence of these N-terminal extra amino acids affected the protein's solubility. 25939548 6 69 theme physicochemical 1074:1088 arg1 properties 1090:1099 the same physicochemical properties 1065:1099 the same physicochemical properties 1065:1099 The OPE produced in the new P. pastoris strain presented the same physicochemical properties than the old one. 25939548 8 70 theme protein 1613:1619 arg1 production 1568:1577 successful production 1557:1577 successful production of soluble and active recombinant protein 1557:1619 Although the yield in S. cerevisiae was lower than that obtained in P. pastoris, this work demonstrates the importance of the choice of the heterologous host for successful production of soluble and active recombinant protein. 25939548 0 71 theme different 62:70 arg1 hosts 72:76 different hosts 62:76 different hosts 62:76 Heterologous expression of a fungal sterol esterase/lipase in different hosts: Effect on solubility, glycosylation and production. 25939548 7 72 theme mature 1342:1347 arg1 protein 1349:1355 the mature protein 1338:1355 the mature protein 1338:1355 An inactive form of the enzyme was produced by the bacterium, but the recombinant esterase from both yeasts was active even after its enzymatic deglycosylation, suggesting that the presence of N-linked carbohydrates in the mature protein is not essential for enzyme activity. 25939548 5 73 theme recombinant 799:809 arg1 protein 811:817 the recombinant protein 795:817 the recombinant protein in the yeast Saccharomyces cerevisiae and in the prokaryotic host Escherichia coli 795:900 We also produced the recombinant protein in the yeast Saccharomyces cerevisiae and in the prokaryotic host Escherichia coli, corroborating that the presence of these N-terminal extra amino acids affected the protein's solubility. 25939548 3 74 from modification 513:524 arg1 sequence 544:551 the N-terminal sequence 529:551 the N-terminal sequence of the protein expressed in Pichia pastoris, which incorporated 4-8 additional amino acids 529:642 This fact owes to a modification in the N-terminal sequence of the protein expressed in Pichia pastoris, which incorporated 4-8 additional amino acids, affecting its aggregation behavior. 25939548 8 75 theme successful 1557:1566 arg1 production 1568:1577 successful production 1557:1577 successful production of soluble and active recombinant protein 1557:1619 Although the yield in S. cerevisiae was lower than that obtained in P. pastoris, this work demonstrates the importance of the choice of the heterologous host for successful production of soluble and active recombinant protein. 25889420 6 0 theme LRR 1026:1028 arg1 domain 1030:1035 the LRR domain 1022:1035 the LRR domain 1022:1035 The hydropathic evaluation of MdPGIP1 indicated a repetitive hydrophobic motif in the LRR domain and a hydrophilic surface area consistent with a globular protein. 25889420 4 1 theme 330 555:557 arg1 nucleotides 529:539 993 nucleotides 525:539 993 nucleotides that encode a 330 amino acid polypeptide 525:580 FINDINGS Analysis of the MdPGIP1 nucleotide sequence revealed that the gene comprises 993 nucleotides that encode a 330 amino acid polypeptide. 25889420 4 1 theme 330 555:557 arg1 polypeptide 570:580 a 330 amino acid polypeptide 553:580 a 330 amino acid polypeptide 553:580 FINDINGS Analysis of the MdPGIP1 nucleotide sequence revealed that the gene comprises 993 nucleotides that encode a 330 amino acid polypeptide. 25889420 9 2 theme curved 1478:1483 arg1 MdPGIP1 1465:1471 MdPGIP1 1465:1471 MdPGIP1 1465:1471 Furthermore, the secondary and tertiary structure of MdPGIP1 was modelled, and revealed that MdPGIP1 is a curved and elongated molecule that contains sheet B1, sheet B2 and 310-helices on its LRR domain. 25889420 9 2 theme curved 1478:1483 arg1 molecule 1499:1506 a curved and elongated molecule 1476:1506 a curved and elongated molecule that contains sheet B1, sheet B2 and 310-helices on its LRR domain 1476:1573 Furthermore, the secondary and tertiary structure of MdPGIP1 was modelled, and revealed that MdPGIP1 is a curved and elongated molecule that contains sheet B1, sheet B2 and 310-helices on its LRR domain. 25889420 4 3 theme acid 565:568 arg1 nucleotides 529:539 993 nucleotides 525:539 993 nucleotides that encode a 330 amino acid polypeptide 525:580 FINDINGS Analysis of the MdPGIP1 nucleotide sequence revealed that the gene comprises 993 nucleotides that encode a 330 amino acid polypeptide. 25889420 4 3 theme acid 565:568 arg1 polypeptide 570:580 a 330 amino acid polypeptide 553:580 a 330 amino acid polypeptide 553:580 FINDINGS Analysis of the MdPGIP1 nucleotide sequence revealed that the gene comprises 993 nucleotides that encode a 330 amino acid polypeptide. 25889420 5 4 theme typical 654:660 arg1 domains 646:652 domains 646:652 domains typical of PGIP proteins, which include a 24 amino acid putative signal peptide, a potential cleavage site [Alanine-Leucine-Serine (ALS)] for the signal peptide, a 238 amino acid leucine-rich repeat (LRR) domain, a 46 amino acid N-terminal domain and a 22 amino acid C-terminal domain 646:937 In silico characterization of the MdPGIP1 polypeptide revealed domains typical of PGIP proteins, which include a 24 amino acid putative signal peptide, a potential cleavage site [Alanine-Leucine-Serine (ALS)] for the signal peptide, a 238 amino acid leucine-rich repeat (LRR) domain, a 46 amino acid N-terminal domain and a 22 amino acid C-terminal domain. 25889420 0 5 theme In 0:1 arg1 analysis 10:17 In silico analysis 0:17 In silico analysis of the polygalacturonase inhibiting protein 1 from apple, Malus domestica. 0:92 In silico analysis of the polygalacturonase inhibiting protein 1 from apple, Malus domestica. 25889420 5 6 theme 238 818:820 arg1 domain 859:864 a 238 amino acid leucine-rich repeat (LRR) domain 816:864 a 238 amino acid leucine-rich repeat (LRR) domain 816:864 In silico characterization of the MdPGIP1 polypeptide revealed domains typical of PGIP proteins, which include a 24 amino acid putative signal peptide, a potential cleavage site [Alanine-Leucine-Serine (ALS)] for the signal peptide, a 238 amino acid leucine-rich repeat (LRR) domain, a 46 amino acid N-terminal domain and a 22 amino acid C-terminal domain. 25889420 6 7 theme globular 1086:1093 arg1 protein 1095:1101 a globular protein 1084:1101 a globular protein 1084:1101 The hydropathic evaluation of MdPGIP1 indicated a repetitive hydrophobic motif in the LRR domain and a hydrophilic surface area consistent with a globular protein. 25889420 5 8 theme MdPGIP1 617:623 arg1 polypeptide 625:635 the MdPGIP1 polypeptide 613:635 the MdPGIP1 polypeptide 613:635 In silico characterization of the MdPGIP1 polypeptide revealed domains typical of PGIP proteins, which include a 24 amino acid putative signal peptide, a potential cleavage site [Alanine-Leucine-Serine (ALS)] for the signal peptide, a 238 amino acid leucine-rich repeat (LRR) domain, a 46 amino acid N-terminal domain and a 22 amino acid C-terminal domain. 25889420 5 9 theme acid 828:831 arg1 domain 859:864 a 238 amino acid leucine-rich repeat (LRR) domain 816:864 a 238 amino acid leucine-rich repeat (LRR) domain 816:864 In silico characterization of the MdPGIP1 polypeptide revealed domains typical of PGIP proteins, which include a 24 amino acid putative signal peptide, a potential cleavage site [Alanine-Leucine-Serine (ALS)] for the signal peptide, a 238 amino acid leucine-rich repeat (LRR) domain, a 46 amino acid N-terminal domain and a 22 amino acid C-terminal domain. 25889420 9 10 theme tertiary 1403:1410 arg1 structure 1412:1420 the secondary and tertiary structure 1385:1420 the secondary and tertiary structure of MdPGIP1 1385:1431 Furthermore, the secondary and tertiary structure of MdPGIP1 was modelled, and revealed that MdPGIP1 is a curved and elongated molecule that contains sheet B1, sheet B2 and 310-helices on its LRR domain. 25889420 5 11 theme amino 872:876 arg1 domain 894:899 a 46 amino acid N-terminal domain 867:899 a 46 amino acid N-terminal domain 867:899 In silico characterization of the MdPGIP1 polypeptide revealed domains typical of PGIP proteins, which include a 24 amino acid putative signal peptide, a potential cleavage site [Alanine-Leucine-Serine (ALS)] for the signal peptide, a 238 amino acid leucine-rich repeat (LRR) domain, a 46 amino acid N-terminal domain and a 22 amino acid C-terminal domain. 25889420 5 12 theme signal 800:805 arg1 peptide 807:813 the signal peptide 796:813 the signal peptide 796:813 In silico characterization of the MdPGIP1 polypeptide revealed domains typical of PGIP proteins, which include a 24 amino acid putative signal peptide, a potential cleavage site [Alanine-Leucine-Serine (ALS)] for the signal peptide, a 238 amino acid leucine-rich repeat (LRR) domain, a 46 amino acid N-terminal domain and a 22 amino acid C-terminal domain. 25889420 5 13 theme 24 696:697 arg1 amino 699:703 amino 699:703 amino 699:703 In silico characterization of the MdPGIP1 polypeptide revealed domains typical of PGIP proteins, which include a 24 amino acid putative signal peptide, a potential cleavage site [Alanine-Leucine-Serine (ALS)] for the signal peptide, a 238 amino acid leucine-rich repeat (LRR) domain, a 46 amino acid N-terminal domain and a 22 amino acid C-terminal domain. 25889420 1 14 theme domestica 196:204 arg1 protein 235:241 the M. domestica polygalacturonase inhibiting protein 1 189:243 the M. domestica polygalacturonase inhibiting protein 1 (MdPGIP1) 189:253 BACKGROUND The Malus domestica polygalacturonase inhibiting protein 1 (MdPGIP1) gene, encoding the M. domestica polygalacturonase inhibiting protein 1 (MdPGIP1), was isolated from the Granny Smith apple cultivar (GenBank accession no. 25889420 1 14 theme domestica 196:204 arg1 MdPGIP1 246:252 MdPGIP1 246:252 MdPGIP1 246:252 BACKGROUND The Malus domestica polygalacturonase inhibiting protein 1 (MdPGIP1) gene, encoding the M. domestica polygalacturonase inhibiting protein 1 (MdPGIP1), was isolated from the Granny Smith apple cultivar (GenBank accession no. 25889420 6 15 with consistent 1068:1077 arg1 protein 1095:1101 a globular protein 1084:1101 a globular protein 1084:1101 The hydropathic evaluation of MdPGIP1 indicated a repetitive hydrophobic motif in the LRR domain and a hydrophilic surface area consistent with a globular protein. 25889420 7 16 link N-linked 1214:1221 arg1 glycosylation 1223:1235 potential N-linked glycosylation 1204:1235 potential N-linked glycosylation of MdPGIP1 1204:1246 The typical consensus glycosylation sequence of Asn-X-Ser/Thr was identified in MdPGIP1, indicating potential N-linked glycosylation of MdPGIP1. 25889420 5 17 theme PGIP 665:668 arg1 proteins 670:677 PGIP proteins 665:677 PGIP proteins 665:677 In silico characterization of the MdPGIP1 polypeptide revealed domains typical of PGIP proteins, which include a 24 amino acid putative signal peptide, a potential cleavage site [Alanine-Leucine-Serine (ALS)] for the signal peptide, a 238 amino acid leucine-rich repeat (LRR) domain, a 46 amino acid N-terminal domain and a 22 amino acid C-terminal domain. 25889420 10 18 theme detected 1717:1724 arg1 differences 1726:1736 the detected differences 1713:1736 the detected differences 1713:1736 CONCLUSION The overall properties of the MdPGIP1 protein is similar to that of the prototypical Phaseolus vulgaris PGIP 2 (PvPGIP2), and the detected differences supported its use in biotechnological applications as an inhibitor of targeted fungal polygalacturonases (PGs). 25889420 1 19 theme Malus 109:113 arg1 gene 174:177 The Malus domestica polygalacturonase inhibiting protein 1 (MdPGIP1) gene 105:177 The Malus domestica polygalacturonase inhibiting protein 1 (MdPGIP1) gene 105:177 BACKGROUND The Malus domestica polygalacturonase inhibiting protein 1 (MdPGIP1) gene, encoding the M. domestica polygalacturonase inhibiting protein 1 (MdPGIP1), was isolated from the Granny Smith apple cultivar (GenBank accession no. 25889420 9 20 theme sheet 1532:1536 arg1 B2 1538:1539 sheet B2 1532:1539 sheet B2 1532:1539 Furthermore, the secondary and tertiary structure of MdPGIP1 was modelled, and revealed that MdPGIP1 is a curved and elongated molecule that contains sheet B1, sheet B2 and 310-helices on its LRR domain. 25889420 10 21 theme biotechnological 1759:1774 arg1 applications 1776:1787 biotechnological applications 1759:1787 biotechnological applications 1759:1787 CONCLUSION The overall properties of the MdPGIP1 protein is similar to that of the prototypical Phaseolus vulgaris PGIP 2 (PvPGIP2), and the detected differences supported its use in biotechnological applications as an inhibitor of targeted fungal polygalacturonases (PGs). 25889420 1 22 theme polygalacturonase 125:141 arg1 gene 174:177 The Malus domestica polygalacturonase inhibiting protein 1 (MdPGIP1) gene 105:177 The Malus domestica polygalacturonase inhibiting protein 1 (MdPGIP1) gene 105:177 BACKGROUND The Malus domestica polygalacturonase inhibiting protein 1 (MdPGIP1) gene, encoding the M. domestica polygalacturonase inhibiting protein 1 (MdPGIP1), was isolated from the Granny Smith apple cultivar (GenBank accession no. 25889420 9 23 from B1 1528:1529 arg1 domain 1568:1573 its LRR domain 1560:1573 its LRR domain 1560:1573 Furthermore, the secondary and tertiary structure of MdPGIP1 was modelled, and revealed that MdPGIP1 is a curved and elongated molecule that contains sheet B1, sheet B2 and 310-helices on its LRR domain. 25889420 6 24 theme hydropathic 944:954 arg1 evaluation 956:965 The hydropathic evaluation 940:965 The hydropathic evaluation of MdPGIP1 940:976 The hydropathic evaluation of MdPGIP1 indicated a repetitive hydrophobic motif in the LRR domain and a hydrophilic surface area consistent with a globular protein. 25889420 8 25 theme non-glycosylated 1271:1286 arg1 MdPGIP1 1288:1294 non-glycosylated MdPGIP1 1271:1294 non-glycosylated MdPGIP1 1271:1294 The molecular mass of non-glycosylated MdPGIP1 was calculated as 36.615 kDa and the theoretical isoelectric point as 6.98. 25889420 5 26 theme repeat 846:851 arg1 domain 859:864 a 238 amino acid leucine-rich repeat (LRR) domain 816:864 a 238 amino acid leucine-rich repeat (LRR) domain 816:864 In silico characterization of the MdPGIP1 polypeptide revealed domains typical of PGIP proteins, which include a 24 amino acid putative signal peptide, a potential cleavage site [Alanine-Leucine-Serine (ALS)] for the signal peptide, a 238 amino acid leucine-rich repeat (LRR) domain, a 46 amino acid N-terminal domain and a 22 amino acid C-terminal domain. 25889420 0 27 from analysis 10:17 arg1 domestica 83:91 apple, Malus domestica 70:91 apple, Malus domestica 70:91 In silico analysis of the polygalacturonase inhibiting protein 1 from apple, Malus domestica. 25889420 0 28 theme apple 70:74 arg1 domestica 83:91 apple, Malus domestica 70:91 apple, Malus domestica 70:91 In silico analysis of the polygalacturonase inhibiting protein 1 from apple, Malus domestica. 25889420 1 29 theme accession 315:323 arg1 no 325:326 GenBank accession no 307:326 the Granny Smith apple cultivar (GenBank accession no 274:326 BACKGROUND The Malus domestica polygalacturonase inhibiting protein 1 (MdPGIP1) gene, encoding the M. domestica polygalacturonase inhibiting protein 1 (MdPGIP1), was isolated from the Granny Smith apple cultivar (GenBank accession no. 25889420 5 30 theme LRR 854:856 arg1 domain 859:864 a 238 amino acid leucine-rich repeat (LRR) domain 816:864 a 238 amino acid leucine-rich repeat (LRR) domain 816:864 In silico characterization of the MdPGIP1 polypeptide revealed domains typical of PGIP proteins, which include a 24 amino acid putative signal peptide, a potential cleavage site [Alanine-Leucine-Serine (ALS)] for the signal peptide, a 238 amino acid leucine-rich repeat (LRR) domain, a 46 amino acid N-terminal domain and a 22 amino acid C-terminal domain. 25889420 4 31 theme sequence 483:490 arg1 Analysis 448:455 FINDINGS Analysis 439:455 FINDINGS Analysis of the MdPGIP1 nucleotide sequence 439:490 FINDINGS Analysis of the MdPGIP1 nucleotide sequence revealed that the gene comprises 993 nucleotides that encode a 330 amino acid polypeptide. 25889420 5 32 theme acid 705:708 arg1 peptide 726:732 a 24 amino acid putative signal peptide 694:732 a 24 amino acid putative signal peptide 694:732 In silico characterization of the MdPGIP1 polypeptide revealed domains typical of PGIP proteins, which include a 24 amino acid putative signal peptide, a potential cleavage site [Alanine-Leucine-Serine (ALS)] for the signal peptide, a 238 amino acid leucine-rich repeat (LRR) domain, a 46 amino acid N-terminal domain and a 22 amino acid C-terminal domain. 25889420 1 33 dep cultivar 297:304 arg1 no 325:326 GenBank accession no 307:326 the Granny Smith apple cultivar (GenBank accession no 274:326 BACKGROUND The Malus domestica polygalacturonase inhibiting protein 1 (MdPGIP1) gene, encoding the M. domestica polygalacturonase inhibiting protein 1 (MdPGIP1), was isolated from the Granny Smith apple cultivar (GenBank accession no. 25889420 3 34 theme enhanced 394:401 arg1 resistance 403:412 enhanced resistance 394:412 enhanced resistance against fungal diseases 394:436 The gene was used to transform tobacco and potato for enhanced resistance against fungal diseases. 25889420 5 35 theme signal 719:724 arg1 peptide 726:732 a 24 amino acid putative signal peptide 694:732 a 24 amino acid putative signal peptide 694:732 In silico characterization of the MdPGIP1 polypeptide revealed domains typical of PGIP proteins, which include a 24 amino acid putative signal peptide, a potential cleavage site [Alanine-Leucine-Serine (ALS)] for the signal peptide, a 238 amino acid leucine-rich repeat (LRR) domain, a 46 amino acid N-terminal domain and a 22 amino acid C-terminal domain. 25889420 0 36 theme polygalacturonase 26:42 arg1 protein 55:61 the polygalacturonase inhibiting protein 1 22:63 the polygalacturonase inhibiting protein 1 from apple, Malus domestica 22:91 In silico analysis of the polygalacturonase inhibiting protein 1 from apple, Malus domestica. 25889420 9 37 theme sheet 1522:1526 arg1 B1 1528:1529 sheet B1 1522:1529 sheet B1 1522:1529 Furthermore, the secondary and tertiary structure of MdPGIP1 was modelled, and revealed that MdPGIP1 is a curved and elongated molecule that contains sheet B1, sheet B2 and 310-helices on its LRR domain. 25889420 8 38 theme theoretical 1333:1343 arg1 mass 1263:1266 The molecular mass 1249:1266 The molecular mass of non-glycosylated MdPGIP1 1249:1294 The molecular mass of non-glycosylated MdPGIP1 was calculated as 36.615 kDa and the theoretical isoelectric point as 6.98. 25889420 8 38 theme theoretical 1333:1343 arg1 point 1357:1361 the theoretical isoelectric point 1329:1361 the theoretical isoelectric point 1329:1361 The molecular mass of non-glycosylated MdPGIP1 was calculated as 36.615 kDa and the theoretical isoelectric point as 6.98. 25889420 10 39 theme overall 1591:1597 arg1 properties 1599:1608 The overall properties 1587:1608 CONCLUSION The overall properties of the MdPGIP1 protein 1576:1631 CONCLUSION The overall properties of the MdPGIP1 protein is similar to that of the prototypical Phaseolus vulgaris PGIP 2 (PvPGIP2), and the detected differences supported its use in biotechnological applications as an inhibitor of targeted fungal polygalacturonases (PGs). 25889420 7 40 theme typical 1108:1114 arg1 sequence 1140:1147 The typical consensus glycosylation sequence 1104:1147 The typical consensus glycosylation sequence of Asn-X-Ser/Thr 1104:1164 The typical consensus glycosylation sequence of Asn-X-Ser/Thr was identified in MdPGIP1, indicating potential N-linked glycosylation of MdPGIP1. 25889420 0 41 dep apple 70:74 arg1 Malus 77:81 Malus 77:81 Malus 77:81 In silico analysis of the polygalacturonase inhibiting protein 1 from apple, Malus domestica. 25889420 6 42 theme repetitive 990:999 arg1 motif 1013:1017 a repetitive hydrophobic motif 988:1017 a repetitive hydrophobic motif in the LRR domain 988:1035 The hydropathic evaluation of MdPGIP1 indicated a repetitive hydrophobic motif in the LRR domain and a hydrophilic surface area consistent with a globular protein. 25889420 5 43 theme N-terminal 883:892 arg1 domain 894:899 a 46 amino acid N-terminal domain 867:899 a 46 amino acid N-terminal domain 867:899 In silico characterization of the MdPGIP1 polypeptide revealed domains typical of PGIP proteins, which include a 24 amino acid putative signal peptide, a potential cleavage site [Alanine-Leucine-Serine (ALS)] for the signal peptide, a 238 amino acid leucine-rich repeat (LRR) domain, a 46 amino acid N-terminal domain and a 22 amino acid C-terminal domain. 25889420 1 44 theme inhibiting 143:152 arg1 gene 174:177 The Malus domestica polygalacturonase inhibiting protein 1 (MdPGIP1) gene 105:177 The Malus domestica polygalacturonase inhibiting protein 1 (MdPGIP1) gene 105:177 BACKGROUND The Malus domestica polygalacturonase inhibiting protein 1 (MdPGIP1) gene, encoding the M. domestica polygalacturonase inhibiting protein 1 (MdPGIP1), was isolated from the Granny Smith apple cultivar (GenBank accession no. 25889420 10 45 theme MdPGIP1 1617:1623 arg1 protein 1625:1631 the MdPGIP1 protein 1613:1631 the MdPGIP1 protein 1613:1631 CONCLUSION The overall properties of the MdPGIP1 protein is similar to that of the prototypical Phaseolus vulgaris PGIP 2 (PvPGIP2), and the detected differences supported its use in biotechnological applications as an inhibitor of targeted fungal polygalacturonases (PGs). 25889420 5 46 theme site 756:759 arg1 [Alanine-Leucine-Serine 761:783 a potential cleavage site [Alanine-Leucine-Serine 735:783 a potential cleavage site [Alanine-Leucine-Serine (ALS)] for the signal peptide 735:813 In silico characterization of the MdPGIP1 polypeptide revealed domains typical of PGIP proteins, which include a 24 amino acid putative signal peptide, a potential cleavage site [Alanine-Leucine-Serine (ALS)] for the signal peptide, a 238 amino acid leucine-rich repeat (LRR) domain, a 46 amino acid N-terminal domain and a 22 amino acid C-terminal domain. 25889420 5 46 theme site 756:759 arg1 ALS 786:788 ALS 786:788 ALS 786:788 In silico characterization of the MdPGIP1 polypeptide revealed domains typical of PGIP proteins, which include a 24 amino acid putative signal peptide, a potential cleavage site [Alanine-Leucine-Serine (ALS)] for the signal peptide, a 238 amino acid leucine-rich repeat (LRR) domain, a 46 amino acid N-terminal domain and a 22 amino acid C-terminal domain. 25889420 0 47 theme inhibiting 44:53 arg1 protein 55:61 the polygalacturonase inhibiting protein 1 22:63 the polygalacturonase inhibiting protein 1 from apple, Malus domestica 22:91 In silico analysis of the polygalacturonase inhibiting protein 1 from apple, Malus domestica. 25889420 1 48 theme apple 291:295 arg1 cultivar 297:304 the Granny Smith apple cultivar 274:304 the Granny Smith apple cultivar (GenBank accession no 274:326 BACKGROUND The Malus domestica polygalacturonase inhibiting protein 1 (MdPGIP1) gene, encoding the M. domestica polygalacturonase inhibiting protein 1 (MdPGIP1), was isolated from the Granny Smith apple cultivar (GenBank accession no. 25889420 6 49 theme surface 1055:1061 arg1 area 1063:1066 a hydrophilic surface area 1041:1066 a hydrophilic surface area consistent with a globular protein 1041:1101 The hydropathic evaluation of MdPGIP1 indicated a repetitive hydrophobic motif in the LRR domain and a hydrophilic surface area consistent with a globular protein. 25889420 10 50 theme polygalacturonases 1824:1841 arg1 inhibitor 1795:1803 an inhibitor 1792:1803 an inhibitor of targeted fungal polygalacturonases (PGs) 1792:1847 CONCLUSION The overall properties of the MdPGIP1 protein is similar to that of the prototypical Phaseolus vulgaris PGIP 2 (PvPGIP2), and the detected differences supported its use in biotechnological applications as an inhibitor of targeted fungal polygalacturonases (PGs). 25889420 1 51 theme polygalacturonase 206:222 arg1 protein 235:241 the M. domestica polygalacturonase inhibiting protein 1 189:243 the M. domestica polygalacturonase inhibiting protein 1 (MdPGIP1) 189:253 BACKGROUND The Malus domestica polygalacturonase inhibiting protein 1 (MdPGIP1) gene, encoding the M. domestica polygalacturonase inhibiting protein 1 (MdPGIP1), was isolated from the Granny Smith apple cultivar (GenBank accession no. 25889420 1 51 theme polygalacturonase 206:222 arg1 MdPGIP1 246:252 MdPGIP1 246:252 MdPGIP1 246:252 BACKGROUND The Malus domestica polygalacturonase inhibiting protein 1 (MdPGIP1) gene, encoding the M. domestica polygalacturonase inhibiting protein 1 (MdPGIP1), was isolated from the Granny Smith apple cultivar (GenBank accession no. 25889420 5 52 theme acid 916:919 arg1 domain 932:937 a 22 amino acid C-terminal domain 905:937 a 22 amino acid C-terminal domain 905:937 In silico characterization of the MdPGIP1 polypeptide revealed domains typical of PGIP proteins, which include a 24 amino acid putative signal peptide, a potential cleavage site [Alanine-Leucine-Serine (ALS)] for the signal peptide, a 238 amino acid leucine-rich repeat (LRR) domain, a 46 amino acid N-terminal domain and a 22 amino acid C-terminal domain. 25889420 1 53 theme protein 154:160 arg1 gene 174:177 The Malus domestica polygalacturonase inhibiting protein 1 (MdPGIP1) gene 105:177 The Malus domestica polygalacturonase inhibiting protein 1 (MdPGIP1) gene 105:177 BACKGROUND The Malus domestica polygalacturonase inhibiting protein 1 (MdPGIP1) gene, encoding the M. domestica polygalacturonase inhibiting protein 1 (MdPGIP1), was isolated from the Granny Smith apple cultivar (GenBank accession no. 25889420 3 54 theme fungal 422:427 arg1 diseases 429:436 fungal diseases 422:436 fungal diseases 422:436 The gene was used to transform tobacco and potato for enhanced resistance against fungal diseases. 25889420 10 55 theme vulgaris 1682:1689 arg1 PGIP 1691:1694 the prototypical Phaseolus vulgaris PGIP 2 1655:1696 the prototypical Phaseolus vulgaris PGIP 2 (PvPGIP2) 1655:1706 CONCLUSION The overall properties of the MdPGIP1 protein is similar to that of the prototypical Phaseolus vulgaris PGIP 2 (PvPGIP2), and the detected differences supported its use in biotechnological applications as an inhibitor of targeted fungal polygalacturonases (PGs). 25889420 10 55 theme vulgaris 1682:1689 arg1 PvPGIP2 1699:1705 PvPGIP2 1699:1705 PvPGIP2 1699:1705 CONCLUSION The overall properties of the MdPGIP1 protein is similar to that of the prototypical Phaseolus vulgaris PGIP 2 (PvPGIP2), and the detected differences supported its use in biotechnological applications as an inhibitor of targeted fungal polygalacturonases (PGs). 25889420 0 56 dep In 0:1 arg1 silico 3:8 silico 3:8 silico 3:8 In silico analysis of the polygalacturonase inhibiting protein 1 from apple, Malus domestica. 25889420 7 57 theme potential 1204:1212 arg1 glycosylation 1223:1235 potential N-linked glycosylation 1204:1235 potential N-linked glycosylation of MdPGIP1 1204:1246 The typical consensus glycosylation sequence of Asn-X-Ser/Thr was identified in MdPGIP1, indicating potential N-linked glycosylation of MdPGIP1. 25889420 5 58 theme polypeptide 625:635 arg1 characterization 593:608 silico characterization 586:608 silico characterization of the MdPGIP1 polypeptide 586:635 In silico characterization of the MdPGIP1 polypeptide revealed domains typical of PGIP proteins, which include a 24 amino acid putative signal peptide, a potential cleavage site [Alanine-Leucine-Serine (ALS)] for the signal peptide, a 238 amino acid leucine-rich repeat (LRR) domain, a 46 amino acid N-terminal domain and a 22 amino acid C-terminal domain. 25889420 10 59 theme prototypical 1659:1670 arg1 PGIP 1691:1694 the prototypical Phaseolus vulgaris PGIP 2 1655:1696 the prototypical Phaseolus vulgaris PGIP 2 (PvPGIP2) 1655:1706 CONCLUSION The overall properties of the MdPGIP1 protein is similar to that of the prototypical Phaseolus vulgaris PGIP 2 (PvPGIP2), and the detected differences supported its use in biotechnological applications as an inhibitor of targeted fungal polygalacturonases (PGs). 25889420 10 59 theme prototypical 1659:1670 arg1 PvPGIP2 1699:1705 PvPGIP2 1699:1705 PvPGIP2 1699:1705 CONCLUSION The overall properties of the MdPGIP1 protein is similar to that of the prototypical Phaseolus vulgaris PGIP 2 (PvPGIP2), and the detected differences supported its use in biotechnological applications as an inhibitor of targeted fungal polygalacturonases (PGs). 25889420 4 60 theme MdPGIP1 464:470 arg1 sequence 483:490 the MdPGIP1 nucleotide sequence 460:490 the MdPGIP1 nucleotide sequence 460:490 FINDINGS Analysis of the MdPGIP1 nucleotide sequence revealed that the gene comprises 993 nucleotides that encode a 330 amino acid polypeptide. 25889420 10 61 dep CONCLUSION 1576:1585 arg1 properties 1599:1608 The overall properties 1587:1608 CONCLUSION The overall properties of the MdPGIP1 protein 1576:1631 CONCLUSION The overall properties of the MdPGIP1 protein is similar to that of the prototypical Phaseolus vulgaris PGIP 2 (PvPGIP2), and the detected differences supported its use in biotechnological applications as an inhibitor of targeted fungal polygalacturonases (PGs). 25889420 1 62 attach isolated 260:267 arg1 cultivar 297:304 the Granny Smith apple cultivar 274:304 the Granny Smith apple cultivar (GenBank accession no 274:326 BACKGROUND The Malus domestica polygalacturonase inhibiting protein 1 (MdPGIP1) gene, encoding the M. domestica polygalacturonase inhibiting protein 1 (MdPGIP1), was isolated from the Granny Smith apple cultivar (GenBank accession no. 25889420 1 62 attach isolated 260:267 arg2 gene 174:177 The Malus domestica polygalacturonase inhibiting protein 1 (MdPGIP1) gene 105:177 The Malus domestica polygalacturonase inhibiting protein 1 (MdPGIP1) gene 105:177 BACKGROUND The Malus domestica polygalacturonase inhibiting protein 1 (MdPGIP1) gene, encoding the M. domestica polygalacturonase inhibiting protein 1 (MdPGIP1), was isolated from the Granny Smith apple cultivar (GenBank accession no. 25889420 9 63 theme secondary 1389:1397 arg1 structure 1412:1420 the secondary and tertiary structure 1385:1420 the secondary and tertiary structure of MdPGIP1 1385:1431 Furthermore, the secondary and tertiary structure of MdPGIP1 was modelled, and revealed that MdPGIP1 is a curved and elongated molecule that contains sheet B1, sheet B2 and 310-helices on its LRR domain. 25889420 4 64 theme amino 559:563 arg1 nucleotides 529:539 993 nucleotides 525:539 993 nucleotides that encode a 330 amino acid polypeptide 525:580 FINDINGS Analysis of the MdPGIP1 nucleotide sequence revealed that the gene comprises 993 nucleotides that encode a 330 amino acid polypeptide. 25889420 4 64 theme amino 559:563 arg1 polypeptide 570:580 a 330 amino acid polypeptide 553:580 a 330 amino acid polypeptide 553:580 FINDINGS Analysis of the MdPGIP1 nucleotide sequence revealed that the gene comprises 993 nucleotides that encode a 330 amino acid polypeptide. 25889420 6 65 from motif 1013:1017 arg1 domain 1030:1035 the LRR domain 1022:1035 the LRR domain 1022:1035 The hydropathic evaluation of MdPGIP1 indicated a repetitive hydrophobic motif in the LRR domain and a hydrophilic surface area consistent with a globular protein. 25889420 1 66 theme MdPGIP1 165:171 arg1 gene 174:177 The Malus domestica polygalacturonase inhibiting protein 1 (MdPGIP1) gene 105:177 The Malus domestica polygalacturonase inhibiting protein 1 (MdPGIP1) gene 105:177 BACKGROUND The Malus domestica polygalacturonase inhibiting protein 1 (MdPGIP1) gene, encoding the M. domestica polygalacturonase inhibiting protein 1 (MdPGIP1), was isolated from the Granny Smith apple cultivar (GenBank accession no. 25889420 5 67 theme potential 737:745 arg1 [Alanine-Leucine-Serine 761:783 a potential cleavage site [Alanine-Leucine-Serine 735:783 a potential cleavage site [Alanine-Leucine-Serine (ALS)] for the signal peptide 735:813 In silico characterization of the MdPGIP1 polypeptide revealed domains typical of PGIP proteins, which include a 24 amino acid putative signal peptide, a potential cleavage site [Alanine-Leucine-Serine (ALS)] for the signal peptide, a 238 amino acid leucine-rich repeat (LRR) domain, a 46 amino acid N-terminal domain and a 22 amino acid C-terminal domain. 25889420 5 67 theme potential 737:745 arg1 ALS 786:788 ALS 786:788 ALS 786:788 In silico characterization of the MdPGIP1 polypeptide revealed domains typical of PGIP proteins, which include a 24 amino acid putative signal peptide, a potential cleavage site [Alanine-Leucine-Serine (ALS)] for the signal peptide, a 238 amino acid leucine-rich repeat (LRR) domain, a 46 amino acid N-terminal domain and a 22 amino acid C-terminal domain. 25889420 5 68 theme amino 822:826 arg1 domain 859:864 a 238 amino acid leucine-rich repeat (LRR) domain 816:864 a 238 amino acid leucine-rich repeat (LRR) domain 816:864 In silico characterization of the MdPGIP1 polypeptide revealed domains typical of PGIP proteins, which include a 24 amino acid putative signal peptide, a potential cleavage site [Alanine-Leucine-Serine (ALS)] for the signal peptide, a 238 amino acid leucine-rich repeat (LRR) domain, a 46 amino acid N-terminal domain and a 22 amino acid C-terminal domain. 25889420 6 69 theme consistent 1068:1077 arg1 area 1063:1066 a hydrophilic surface area 1041:1066 a hydrophilic surface area consistent with a globular protein 1041:1101 The hydropathic evaluation of MdPGIP1 indicated a repetitive hydrophobic motif in the LRR domain and a hydrophilic surface area consistent with a globular protein. 25889420 9 70 theme elongated 1489:1497 arg1 MdPGIP1 1465:1471 MdPGIP1 1465:1471 MdPGIP1 1465:1471 Furthermore, the secondary and tertiary structure of MdPGIP1 was modelled, and revealed that MdPGIP1 is a curved and elongated molecule that contains sheet B1, sheet B2 and 310-helices on its LRR domain. 25889420 9 70 theme elongated 1489:1497 arg1 molecule 1499:1506 a curved and elongated molecule 1476:1506 a curved and elongated molecule that contains sheet B1, sheet B2 and 310-helices on its LRR domain 1476:1573 Furthermore, the secondary and tertiary structure of MdPGIP1 was modelled, and revealed that MdPGIP1 is a curved and elongated molecule that contains sheet B1, sheet B2 and 310-helices on its LRR domain. 25889420 7 71 theme MdPGIP1 1240:1246 arg1 glycosylation 1223:1235 potential N-linked glycosylation 1204:1235 potential N-linked glycosylation of MdPGIP1 1204:1246 The typical consensus glycosylation sequence of Asn-X-Ser/Thr was identified in MdPGIP1, indicating potential N-linked glycosylation of MdPGIP1. 25889420 9 72 theme MdPGIP1 1425:1431 arg1 structure 1412:1420 the secondary and tertiary structure 1385:1420 the secondary and tertiary structure of MdPGIP1 1385:1431 Furthermore, the secondary and tertiary structure of MdPGIP1 was modelled, and revealed that MdPGIP1 is a curved and elongated molecule that contains sheet B1, sheet B2 and 310-helices on its LRR domain. 25889420 1 73 theme M. 193:194 arg1 protein 235:241 the M. domestica polygalacturonase inhibiting protein 1 189:243 the M. domestica polygalacturonase inhibiting protein 1 (MdPGIP1) 189:253 BACKGROUND The Malus domestica polygalacturonase inhibiting protein 1 (MdPGIP1) gene, encoding the M. domestica polygalacturonase inhibiting protein 1 (MdPGIP1), was isolated from the Granny Smith apple cultivar (GenBank accession no. 25889420 1 73 theme M. 193:194 arg1 MdPGIP1 246:252 MdPGIP1 246:252 MdPGIP1 246:252 BACKGROUND The Malus domestica polygalacturonase inhibiting protein 1 (MdPGIP1) gene, encoding the M. domestica polygalacturonase inhibiting protein 1 (MdPGIP1), was isolated from the Granny Smith apple cultivar (GenBank accession no. 25889420 5 74 theme proteins 670:677 arg1 typical 654:660 typical 654:660 typical 654:660 In silico characterization of the MdPGIP1 polypeptide revealed domains typical of PGIP proteins, which include a 24 amino acid putative signal peptide, a potential cleavage site [Alanine-Leucine-Serine (ALS)] for the signal peptide, a 238 amino acid leucine-rich repeat (LRR) domain, a 46 amino acid N-terminal domain and a 22 amino acid C-terminal domain. 25889420 9 75 theme LRR 1564:1566 arg1 domain 1568:1573 its LRR domain 1560:1573 its LRR domain 1560:1573 Furthermore, the secondary and tertiary structure of MdPGIP1 was modelled, and revealed that MdPGIP1 is a curved and elongated molecule that contains sheet B1, sheet B2 and 310-helices on its LRR domain. 25889420 1 76 theme domestica 115:123 arg1 gene 174:177 The Malus domestica polygalacturonase inhibiting protein 1 (MdPGIP1) gene 105:177 The Malus domestica polygalacturonase inhibiting protein 1 (MdPGIP1) gene 105:177 BACKGROUND The Malus domestica polygalacturonase inhibiting protein 1 (MdPGIP1) gene, encoding the M. domestica polygalacturonase inhibiting protein 1 (MdPGIP1), was isolated from the Granny Smith apple cultivar (GenBank accession no. 25889420 9 77 from B2 1538:1539 arg1 domain 1568:1573 its LRR domain 1560:1573 its LRR domain 1560:1573 Furthermore, the secondary and tertiary structure of MdPGIP1 was modelled, and revealed that MdPGIP1 is a curved and elongated molecule that contains sheet B1, sheet B2 and 310-helices on its LRR domain. 25889420 0 78 from domestica 83:91 arg1 analysis 10:17 In silico analysis 0:17 In silico analysis of the polygalacturonase inhibiting protein 1 from apple, Malus domestica. 0:92 In silico analysis of the polygalacturonase inhibiting protein 1 from apple, Malus domestica. 25889420 0 78 from domestica 83:91 arg1 protein 55:61 the polygalacturonase inhibiting protein 1 22:63 the polygalacturonase inhibiting protein 1 from apple, Malus domestica 22:91 In silico analysis of the polygalacturonase inhibiting protein 1 from apple, Malus domestica. 25889420 8 79 theme molecular 1253:1261 arg1 36.615 kDa 1314:1323 36.615 kDa 1314:1323 36.615 kDa 1314:1323 The molecular mass of non-glycosylated MdPGIP1 was calculated as 36.615 kDa and the theoretical isoelectric point as 6.98. 25889420 8 79 theme molecular 1253:1261 arg1 mass 1263:1266 The molecular mass 1249:1266 The molecular mass of non-glycosylated MdPGIP1 1249:1294 The molecular mass of non-glycosylated MdPGIP1 was calculated as 36.615 kDa and the theoretical isoelectric point as 6.98. 25889420 8 79 theme molecular 1253:1261 arg1 6.98 1366:1369 6.98 1366:1369 6.98 1366:1369 The molecular mass of non-glycosylated MdPGIP1 was calculated as 36.615 kDa and the theoretical isoelectric point as 6.98. 25889420 8 79 theme molecular 1253:1261 arg1 point 1357:1361 the theoretical isoelectric point 1329:1361 the theoretical isoelectric point 1329:1361 The molecular mass of non-glycosylated MdPGIP1 was calculated as 36.615 kDa and the theoretical isoelectric point as 6.98. 25889420 7 80 theme N-linked 1214:1221 arg1 glycosylation 1223:1235 potential N-linked glycosylation 1204:1235 potential N-linked glycosylation of MdPGIP1 1204:1246 The typical consensus glycosylation sequence of Asn-X-Ser/Thr was identified in MdPGIP1, indicating potential N-linked glycosylation of MdPGIP1. 25889420 5 81 theme leucine-rich 833:844 arg1 domain 859:864 a 238 amino acid leucine-rich repeat (LRR) domain 816:864 a 238 amino acid leucine-rich repeat (LRR) domain 816:864 In silico characterization of the MdPGIP1 polypeptide revealed domains typical of PGIP proteins, which include a 24 amino acid putative signal peptide, a potential cleavage site [Alanine-Leucine-Serine (ALS)] for the signal peptide, a 238 amino acid leucine-rich repeat (LRR) domain, a 46 amino acid N-terminal domain and a 22 amino acid C-terminal domain. 25889420 4 82 theme nucleotide 472:481 arg1 sequence 483:490 the MdPGIP1 nucleotide sequence 460:490 the MdPGIP1 nucleotide sequence 460:490 FINDINGS Analysis of the MdPGIP1 nucleotide sequence revealed that the gene comprises 993 nucleotides that encode a 330 amino acid polypeptide. 25889420 1 83 dep BACKGROUND 94:103 arg1 isolated 260:267 isolated 260:267 was isolated from the Granny Smith apple cultivar (GenBank accession no 256:326 BACKGROUND The Malus domestica polygalacturonase inhibiting protein 1 (MdPGIP1) gene, encoding the M. domestica polygalacturonase inhibiting protein 1 (MdPGIP1), was isolated from the Granny Smith apple cultivar (GenBank accession no. 25889420 7 84 theme Asn-X-Ser/Thr 1152:1164 arg1 sequence 1140:1147 The typical consensus glycosylation sequence 1104:1147 The typical consensus glycosylation sequence of Asn-X-Ser/Thr 1104:1164 The typical consensus glycosylation sequence of Asn-X-Ser/Thr was identified in MdPGIP1, indicating potential N-linked glycosylation of MdPGIP1. 25889420 1 85 theme GenBank 307:313 arg1 no 325:326 GenBank accession no 307:326 the Granny Smith apple cultivar (GenBank accession no 274:326 BACKGROUND The Malus domestica polygalacturonase inhibiting protein 1 (MdPGIP1) gene, encoding the M. domestica polygalacturonase inhibiting protein 1 (MdPGIP1), was isolated from the Granny Smith apple cultivar (GenBank accession no. 25889420 8 86 theme MdPGIP1 1288:1294 arg1 36.615 kDa 1314:1323 36.615 kDa 1314:1323 36.615 kDa 1314:1323 The molecular mass of non-glycosylated MdPGIP1 was calculated as 36.615 kDa and the theoretical isoelectric point as 6.98. 25889420 8 86 theme MdPGIP1 1288:1294 arg1 mass 1263:1266 The molecular mass 1249:1266 The molecular mass of non-glycosylated MdPGIP1 1249:1294 The molecular mass of non-glycosylated MdPGIP1 was calculated as 36.615 kDa and the theoretical isoelectric point as 6.98. 25889420 8 86 theme MdPGIP1 1288:1294 arg1 6.98 1366:1369 6.98 1366:1369 6.98 1366:1369 The molecular mass of non-glycosylated MdPGIP1 was calculated as 36.615 kDa and the theoretical isoelectric point as 6.98. 25889420 8 86 theme MdPGIP1 1288:1294 arg1 point 1357:1361 the theoretical isoelectric point 1329:1361 the theoretical isoelectric point 1329:1361 The molecular mass of non-glycosylated MdPGIP1 was calculated as 36.615 kDa and the theoretical isoelectric point as 6.98. 25889420 5 87 theme amino 699:703 arg1 peptide 726:732 a 24 amino acid putative signal peptide 694:732 a 24 amino acid putative signal peptide 694:732 In silico characterization of the MdPGIP1 polypeptide revealed domains typical of PGIP proteins, which include a 24 amino acid putative signal peptide, a potential cleavage site [Alanine-Leucine-Serine (ALS)] for the signal peptide, a 238 amino acid leucine-rich repeat (LRR) domain, a 46 amino acid N-terminal domain and a 22 amino acid C-terminal domain. 25889420 7 88 theme consensus 1116:1124 arg1 sequence 1140:1147 The typical consensus glycosylation sequence 1104:1147 The typical consensus glycosylation sequence of Asn-X-Ser/Thr 1104:1164 The typical consensus glycosylation sequence of Asn-X-Ser/Thr was identified in MdPGIP1, indicating potential N-linked glycosylation of MdPGIP1. 25889420 8 89 gly non-glycosylated 1271:1286 arg1 MdPGIP1 1288:1294 non-glycosylated MdPGIP1 1271:1294 non-glycosylated MdPGIP1 1271:1294 The molecular mass of non-glycosylated MdPGIP1 was calculated as 36.615 kDa and the theoretical isoelectric point as 6.98. 25889420 5 90 theme silico 586:591 arg1 characterization 593:608 silico characterization 586:608 silico characterization of the MdPGIP1 polypeptide 586:635 In silico characterization of the MdPGIP1 polypeptide revealed domains typical of PGIP proteins, which include a 24 amino acid putative signal peptide, a potential cleavage site [Alanine-Leucine-Serine (ALS)] for the signal peptide, a 238 amino acid leucine-rich repeat (LRR) domain, a 46 amino acid N-terminal domain and a 22 amino acid C-terminal domain. 25889420 5 91 theme putative 710:717 arg1 peptide 726:732 a 24 amino acid putative signal peptide 694:732 a 24 amino acid putative signal peptide 694:732 In silico characterization of the MdPGIP1 polypeptide revealed domains typical of PGIP proteins, which include a 24 amino acid putative signal peptide, a potential cleavage site [Alanine-Leucine-Serine (ALS)] for the signal peptide, a 238 amino acid leucine-rich repeat (LRR) domain, a 46 amino acid N-terminal domain and a 22 amino acid C-terminal domain. 25889420 4 92 theme FINDINGS 439:446 arg1 Analysis 448:455 FINDINGS Analysis 439:455 FINDINGS Analysis of the MdPGIP1 nucleotide sequence 439:490 FINDINGS Analysis of the MdPGIP1 nucleotide sequence revealed that the gene comprises 993 nucleotides that encode a 330 amino acid polypeptide. 25889420 6 93 theme hydrophobic 1001:1011 arg1 motif 1013:1017 a repetitive hydrophobic motif 988:1017 a repetitive hydrophobic motif in the LRR domain 988:1035 The hydropathic evaluation of MdPGIP1 indicated a repetitive hydrophobic motif in the LRR domain and a hydrophilic surface area consistent with a globular protein. 25889420 10 94 theme targeted 1808:1815 arg1 PGs 1844:1846 PGs 1844:1846 PGs 1844:1846 CONCLUSION The overall properties of the MdPGIP1 protein is similar to that of the prototypical Phaseolus vulgaris PGIP 2 (PvPGIP2), and the detected differences supported its use in biotechnological applications as an inhibitor of targeted fungal polygalacturonases (PGs). 25889420 10 94 theme targeted 1808:1815 arg1 polygalacturonases 1824:1841 targeted fungal polygalacturonases 1808:1841 targeted fungal polygalacturonases (PGs) 1808:1847 CONCLUSION The overall properties of the MdPGIP1 protein is similar to that of the prototypical Phaseolus vulgaris PGIP 2 (PvPGIP2), and the detected differences supported its use in biotechnological applications as an inhibitor of targeted fungal polygalacturonases (PGs). 25889420 5 95 theme acid 878:881 arg1 domain 894:899 a 46 amino acid N-terminal domain 867:899 a 46 amino acid N-terminal domain 867:899 In silico characterization of the MdPGIP1 polypeptide revealed domains typical of PGIP proteins, which include a 24 amino acid putative signal peptide, a potential cleavage site [Alanine-Leucine-Serine (ALS)] for the signal peptide, a 238 amino acid leucine-rich repeat (LRR) domain, a 46 amino acid N-terminal domain and a 22 amino acid C-terminal domain. 25889420 10 96 from use 1752:1754 arg1 applications 1776:1787 biotechnological applications 1759:1787 biotechnological applications 1759:1787 CONCLUSION The overall properties of the MdPGIP1 protein is similar to that of the prototypical Phaseolus vulgaris PGIP 2 (PvPGIP2), and the detected differences supported its use in biotechnological applications as an inhibitor of targeted fungal polygalacturonases (PGs). 25889420 8 97 theme isoelectric 1345:1355 arg1 mass 1263:1266 The molecular mass 1249:1266 The molecular mass of non-glycosylated MdPGIP1 1249:1294 The molecular mass of non-glycosylated MdPGIP1 was calculated as 36.615 kDa and the theoretical isoelectric point as 6.98. 25889420 8 97 theme isoelectric 1345:1355 arg1 point 1357:1361 the theoretical isoelectric point 1329:1361 the theoretical isoelectric point 1329:1361 The molecular mass of non-glycosylated MdPGIP1 was calculated as 36.615 kDa and the theoretical isoelectric point as 6.98. 25889420 10 98 theme protein 1625:1631 arg1 properties 1599:1608 The overall properties 1587:1608 CONCLUSION The overall properties of the MdPGIP1 protein 1576:1631 CONCLUSION The overall properties of the MdPGIP1 protein is similar to that of the prototypical Phaseolus vulgaris PGIP 2 (PvPGIP2), and the detected differences supported its use in biotechnological applications as an inhibitor of targeted fungal polygalacturonases (PGs). 25889420 5 99 theme cleavage 747:754 arg1 [Alanine-Leucine-Serine 761:783 a potential cleavage site [Alanine-Leucine-Serine 735:783 a potential cleavage site [Alanine-Leucine-Serine (ALS)] for the signal peptide 735:813 In silico characterization of the MdPGIP1 polypeptide revealed domains typical of PGIP proteins, which include a 24 amino acid putative signal peptide, a potential cleavage site [Alanine-Leucine-Serine (ALS)] for the signal peptide, a 238 amino acid leucine-rich repeat (LRR) domain, a 46 amino acid N-terminal domain and a 22 amino acid C-terminal domain. 25889420 5 99 theme cleavage 747:754 arg1 ALS 786:788 ALS 786:788 ALS 786:788 In silico characterization of the MdPGIP1 polypeptide revealed domains typical of PGIP proteins, which include a 24 amino acid putative signal peptide, a potential cleavage site [Alanine-Leucine-Serine (ALS)] for the signal peptide, a 238 amino acid leucine-rich repeat (LRR) domain, a 46 amino acid N-terminal domain and a 22 amino acid C-terminal domain. 25889420 3 100 used used 353:356 arg2 gene 344:347 The gene 340:347 The gene 340:347 The gene was used to transform tobacco and potato for enhanced resistance against fungal diseases. 25889420 9 101 from 310-helices 1545:1555 arg1 domain 1568:1573 its LRR domain 1560:1573 its LRR domain 1560:1573 Furthermore, the secondary and tertiary structure of MdPGIP1 was modelled, and revealed that MdPGIP1 is a curved and elongated molecule that contains sheet B1, sheet B2 and 310-helices on its LRR domain. 25889420 6 102 theme MdPGIP1 970:976 arg1 evaluation 956:965 The hydropathic evaluation 940:965 The hydropathic evaluation of MdPGIP1 940:976 The hydropathic evaluation of MdPGIP1 indicated a repetitive hydrophobic motif in the LRR domain and a hydrophilic surface area consistent with a globular protein. 25889420 7 103 theme glycosylation 1126:1138 arg1 sequence 1140:1147 The typical consensus glycosylation sequence 1104:1147 The typical consensus glycosylation sequence of Asn-X-Ser/Thr 1104:1164 The typical consensus glycosylation sequence of Asn-X-Ser/Thr was identified in MdPGIP1, indicating potential N-linked glycosylation of MdPGIP1. 25889420 0 104 theme protein 55:61 arg1 analysis 10:17 In silico analysis 0:17 In silico analysis of the polygalacturonase inhibiting protein 1 from apple, Malus domestica. 0:92 In silico analysis of the polygalacturonase inhibiting protein 1 from apple, Malus domestica. 25889420 1 105 theme Smith 285:289 arg1 cultivar 297:304 the Granny Smith apple cultivar 274:304 the Granny Smith apple cultivar (GenBank accession no 274:326 BACKGROUND The Malus domestica polygalacturonase inhibiting protein 1 (MdPGIP1) gene, encoding the M. domestica polygalacturonase inhibiting protein 1 (MdPGIP1), was isolated from the Granny Smith apple cultivar (GenBank accession no. 25889420 6 106 from area 1063:1066 arg1 domain 1030:1035 the LRR domain 1022:1035 the LRR domain 1022:1035 The hydropathic evaluation of MdPGIP1 indicated a repetitive hydrophobic motif in the LRR domain and a hydrophilic surface area consistent with a globular protein. 25889420 7 107 gly glycosylation 1223:1235 arg1 MdPGIP1 1240:1246 MdPGIP1 1240:1246 MdPGIP1 1240:1246 The typical consensus glycosylation sequence of Asn-X-Ser/Thr was identified in MdPGIP1, indicating potential N-linked glycosylation of MdPGIP1. 25889420 5 108 theme amino 910:914 arg1 domain 932:937 a 22 amino acid C-terminal domain 905:937 a 22 amino acid C-terminal domain 905:937 In silico characterization of the MdPGIP1 polypeptide revealed domains typical of PGIP proteins, which include a 24 amino acid putative signal peptide, a potential cleavage site [Alanine-Leucine-Serine (ALS)] for the signal peptide, a 238 amino acid leucine-rich repeat (LRR) domain, a 46 amino acid N-terminal domain and a 22 amino acid C-terminal domain. 25889420 6 109 theme hydrophilic 1043:1053 arg1 area 1063:1066 a hydrophilic surface area 1041:1066 a hydrophilic surface area consistent with a globular protein 1041:1101 The hydropathic evaluation of MdPGIP1 indicated a repetitive hydrophobic motif in the LRR domain and a hydrophilic surface area consistent with a globular protein. 25889420 10 110 theme fungal 1817:1822 arg1 PGs 1844:1846 PGs 1844:1846 PGs 1844:1846 CONCLUSION The overall properties of the MdPGIP1 protein is similar to that of the prototypical Phaseolus vulgaris PGIP 2 (PvPGIP2), and the detected differences supported its use in biotechnological applications as an inhibitor of targeted fungal polygalacturonases (PGs). 25889420 10 110 theme fungal 1817:1822 arg1 polygalacturonases 1824:1841 targeted fungal polygalacturonases 1808:1841 targeted fungal polygalacturonases (PGs) 1808:1847 CONCLUSION The overall properties of the MdPGIP1 protein is similar to that of the prototypical Phaseolus vulgaris PGIP 2 (PvPGIP2), and the detected differences supported its use in biotechnological applications as an inhibitor of targeted fungal polygalacturonases (PGs). 25889420 1 111 theme inhibiting 224:233 arg1 protein 235:241 the M. domestica polygalacturonase inhibiting protein 1 189:243 the M. domestica polygalacturonase inhibiting protein 1 (MdPGIP1) 189:253 BACKGROUND The Malus domestica polygalacturonase inhibiting protein 1 (MdPGIP1) gene, encoding the M. domestica polygalacturonase inhibiting protein 1 (MdPGIP1), was isolated from the Granny Smith apple cultivar (GenBank accession no. 25889420 1 111 theme inhibiting 224:233 arg1 MdPGIP1 246:252 MdPGIP1 246:252 MdPGIP1 246:252 BACKGROUND The Malus domestica polygalacturonase inhibiting protein 1 (MdPGIP1) gene, encoding the M. domestica polygalacturonase inhibiting protein 1 (MdPGIP1), was isolated from the Granny Smith apple cultivar (GenBank accession no. 25889420 5 112 theme C-terminal 921:930 arg1 domain 932:937 a 22 amino acid C-terminal domain 905:937 a 22 amino acid C-terminal domain 905:937 In silico characterization of the MdPGIP1 polypeptide revealed domains typical of PGIP proteins, which include a 24 amino acid putative signal peptide, a potential cleavage site [Alanine-Leucine-Serine (ALS)] for the signal peptide, a 238 amino acid leucine-rich repeat (LRR) domain, a 46 amino acid N-terminal domain and a 22 amino acid C-terminal domain. 25889420 9 113 contain contains 1513:1520 arg2 B2 1538:1539 sheet B2 1532:1539 sheet B2 1532:1539 Furthermore, the secondary and tertiary structure of MdPGIP1 was modelled, and revealed that MdPGIP1 is a curved and elongated molecule that contains sheet B1, sheet B2 and 310-helices on its LRR domain. 25889420 9 113 contain contains 1513:1520 arg1 MdPGIP1 1465:1471 MdPGIP1 1465:1471 MdPGIP1 1465:1471 Furthermore, the secondary and tertiary structure of MdPGIP1 was modelled, and revealed that MdPGIP1 is a curved and elongated molecule that contains sheet B1, sheet B2 and 310-helices on its LRR domain. 25889420 9 113 contain contains 1513:1520 arg1 molecule 1499:1506 a curved and elongated molecule 1476:1506 a curved and elongated molecule that contains sheet B1, sheet B2 and 310-helices on its LRR domain 1476:1573 Furthermore, the secondary and tertiary structure of MdPGIP1 was modelled, and revealed that MdPGIP1 is a curved and elongated molecule that contains sheet B1, sheet B2 and 310-helices on its LRR domain. 25889420 9 113 contain contains 1513:1520 arg2 B1 1528:1529 sheet B1 1522:1529 sheet B1 1522:1529 Furthermore, the secondary and tertiary structure of MdPGIP1 was modelled, and revealed that MdPGIP1 is a curved and elongated molecule that contains sheet B1, sheet B2 and 310-helices on its LRR domain. 25889420 9 113 contain contains 1513:1520 arg2 310-helices 1545:1555 310-helices 1545:1555 310-helices 1545:1555 Furthermore, the secondary and tertiary structure of MdPGIP1 was modelled, and revealed that MdPGIP1 is a curved and elongated molecule that contains sheet B1, sheet B2 and 310-helices on its LRR domain. 25889420 10 114 theme Phaseolus 1672:1680 arg1 PGIP 1691:1694 the prototypical Phaseolus vulgaris PGIP 2 1655:1696 the prototypical Phaseolus vulgaris PGIP 2 (PvPGIP2) 1655:1706 CONCLUSION The overall properties of the MdPGIP1 protein is similar to that of the prototypical Phaseolus vulgaris PGIP 2 (PvPGIP2), and the detected differences supported its use in biotechnological applications as an inhibitor of targeted fungal polygalacturonases (PGs). 25889420 10 114 theme Phaseolus 1672:1680 arg1 PvPGIP2 1699:1705 PvPGIP2 1699:1705 PvPGIP2 1699:1705 CONCLUSION The overall properties of the MdPGIP1 protein is similar to that of the prototypical Phaseolus vulgaris PGIP 2 (PvPGIP2), and the detected differences supported its use in biotechnological applications as an inhibitor of targeted fungal polygalacturonases (PGs). 25809283 0 0 theme mass 90:93 arg1 spectrometry 95:106 MALDI mass spectrometry 84:106 MALDI mass spectrometry 84:106 Comparative glycoprofiling of HIV gp120 immunogens by capillary electrophoresis and MALDI mass spectrometry. 25809283 7 1 theme future 1151:1156 arg1 strategies 1166:1175 future vaccine strategies 1151:1175 future vaccine strategies 1151:1175 Such effects are likely to influence the immunogenicity of various Env immunogens and should be considered for future vaccine strategies, emphasizing the importance of the glycosylation analysis approach described in this paper. 25809283 2 2 theme Env 323:325 arg1 subunit 312:318 the gp120 subunit 302:318 the gp120 subunit of Env 302:325 Vaccine trials with the gp120 subunit of Env are ongoing, with the recent RV144 trial showing moderate efficacy. 25809283 1 3 theme virus 231:235 arg1 surface 216:222 the surface 212:222 the surface of the virus 212:235 The human immunodeficiency virus (HIV) envelope glycoprotein (Env) is the primary antigenic feature on the surface of the virus and is of key importance in HIV vaccinology. 25809283 0 4 theme MALDI 84:88 arg1 spectrometry 95:106 MALDI mass spectrometry 84:106 MALDI mass spectrometry 84:106 Comparative glycoprofiling of HIV gp120 immunogens by capillary electrophoresis and MALDI mass spectrometry. 25809283 6 5 theme glycosylation 1016:1028 arg1 patterns 1030:1037 the overall glycosylation patterns 1004:1037 the overall glycosylation patterns 1004:1037 This study revealed that the addition of specific tags, such as the herpes simplex virus glycoprotein D tag used in the RV144 trial, had significant effects on the overall glycosylation patterns. 25809283 6 6 theme virus 927:931 arg1 tag 948:950 the herpes simplex virus glycoprotein D tag 908:950 the herpes simplex virus glycoprotein D tag used in the RV144 trial 908:974 This study revealed that the addition of specific tags, such as the herpes simplex virus glycoprotein D tag used in the RV144 trial, had significant effects on the overall glycosylation patterns. 25809283 6 7 theme D 946:946 arg1 tag 948:950 the herpes simplex virus glycoprotein D tag 908:950 the herpes simplex virus glycoprotein D tag used in the RV144 trial 908:974 This study revealed that the addition of specific tags, such as the herpes simplex virus glycoprotein D tag used in the RV144 trial, had significant effects on the overall glycosylation patterns. 25809283 3 8 theme humoral 484:490 arg1 response 499:506 the host's humoral immune response 473:506 the host's humoral immune response 473:506 gp120 is densely covered with N-linked glycans that are thought to help evade the host's humoral immune response. 25809283 2 9 with trials 290:295 arg1 subunit 312:318 the gp120 subunit 302:318 the gp120 subunit of Env 302:325 Vaccine trials with the gp120 subunit of Env are ongoing, with the recent RV144 trial showing moderate efficacy. 25809283 3 10 link N-linked 425:432 arg1 glycans 434:440 N-linked glycans 425:440 N-linked glycans that are thought to help evade the host's humoral immune response 425:506 gp120 is densely covered with N-linked glycans that are thought to help evade the host's humoral immune response. 25809283 3 11 theme immune 492:497 arg1 response 499:506 the host's humoral immune response 473:506 the host's humoral immune response 473:506 gp120 is densely covered with N-linked glycans that are thought to help evade the host's humoral immune response. 25809283 4 12 theme global 527:532 arg1 patterns 548:555 the global glycosylation patterns 523:555 the global glycosylation patterns 523:555 To assess how the global glycosylation patterns vary between gp120 constructs, the glycan profiles of several gp120s were examined by CE with LIF detection and MALDI-MS. 25809283 4 13 theme LIF 651:653 arg1 detection 655:663 LIF detection 651:663 LIF detection 651:663 To assess how the global glycosylation patterns vary between gp120 constructs, the glycan profiles of several gp120s were examined by CE with LIF detection and MALDI-MS. 25809283 3 14 theme N-linked 425:432 arg1 glycans 434:440 N-linked glycans 425:440 N-linked glycans that are thought to help evade the host's humoral immune response 425:506 gp120 is densely covered with N-linked glycans that are thought to help evade the host's humoral immune response. 25809283 6 15 theme RV144 964:968 arg1 trial 970:974 the RV144 trial 960:974 the RV144 trial 960:974 This study revealed that the addition of specific tags, such as the herpes simplex virus glycoprotein D tag used in the RV144 trial, had significant effects on the overall glycosylation patterns. 25809283 5 16 theme different 826:834 arg1 clades 836:841 different clades 826:841 different clades 826:841 The glycosylation profiles were found to be similar for chronic versus transmitter/founder isolates and only varied moderately between gp120s from different clades. 25809283 2 17 theme recent 349:354 arg1 trial 362:366 the recent RV144 trial 345:366 the recent RV144 trial showing moderate efficacy 345:392 Vaccine trials with the gp120 subunit of Env are ongoing, with the recent RV144 trial showing moderate efficacy. 25809283 5 18 theme glycosylation 683:695 arg1 similar 723:729 similar 723:729 similar 723:729 The glycosylation profiles were found to be similar for chronic versus transmitter/founder isolates and only varied moderately between gp120s from different clades. 25809283 5 18 theme glycosylation 683:695 arg1 profiles 697:704 The glycosylation profiles 679:704 The glycosylation profiles 679:704 The glycosylation profiles were found to be similar for chronic versus transmitter/founder isolates and only varied moderately between gp120s from different clades. 25809283 6 19 contain had 977:979 arg1 addition 873:880 the addition 869:880 the addition of specific tags, such as the herpes simplex virus glycoprotein D tag used in the RV144 trial, 869:975 This study revealed that the addition of specific tags, such as the herpes simplex virus glycoprotein D tag used in the RV144 trial, had significant effects on the overall glycosylation patterns. 25809283 6 19 contain had 977:979 arg2 effects 993:999 significant effects 981:999 significant effects 981:999 This study revealed that the addition of specific tags, such as the herpes simplex virus glycoprotein D tag used in the RV144 trial, had significant effects on the overall glycosylation patterns. 25809283 7 20 theme Such 1040:1043 arg1 effects 1045:1051 Such effects 1040:1051 Such effects 1040:1051 Such effects are likely to influence the immunogenicity of various Env immunogens and should be considered for future vaccine strategies, emphasizing the importance of the glycosylation analysis approach described in this paper. 25809283 5 21 theme transmitter/founder 750:768 arg1 isolates 770:777 chronic versus transmitter/founder isolates 735:777 chronic versus transmitter/founder isolates 735:777 The glycosylation profiles were found to be similar for chronic versus transmitter/founder isolates and only varied moderately between gp120s from different clades. 25809283 7 22 theme immunogens 1111:1120 arg1 immunogenicity 1081:1094 the immunogenicity 1077:1094 the immunogenicity of various Env immunogens 1077:1120 Such effects are likely to influence the immunogenicity of various Env immunogens and should be considered for future vaccine strategies, emphasizing the importance of the glycosylation analysis approach described in this paper. 25809283 1 23 theme HIV 265:267 arg1 vaccinology 269:279 HIV vaccinology 265:279 HIV vaccinology 265:279 The human immunodeficiency virus (HIV) envelope glycoprotein (Env) is the primary antigenic feature on the surface of the virus and is of key importance in HIV vaccinology. 25809283 6 24 theme overall 1008:1014 arg1 patterns 1030:1037 the overall glycosylation patterns 1004:1037 the overall glycosylation patterns 1004:1037 This study revealed that the addition of specific tags, such as the herpes simplex virus glycoprotein D tag used in the RV144 trial, had significant effects on the overall glycosylation patterns. 25809283 6 25 theme simplex 919:925 arg1 virus 927:931 the herpes simplex virus 908:931 the herpes simplex virus glycoprotein D tag used in the RV144 trial 908:974 This study revealed that the addition of specific tags, such as the herpes simplex virus glycoprotein D tag used in the RV144 trial, had significant effects on the overall glycosylation patterns. 25809283 4 26 theme gp120s 619:624 arg1 profiles 599:606 the glycan profiles 588:606 the glycan profiles of several gp120s 588:624 To assess how the global glycosylation patterns vary between gp120 constructs, the glycan profiles of several gp120s were examined by CE with LIF detection and MALDI-MS. 25809283 0 27 theme Comparative 0:10 arg1 glycoprofiling 12:25 Comparative glycoprofiling 0:25 Comparative glycoprofiling of HIV gp120 0:38 Comparative glycoprofiling of HIV gp120 immunogens by capillary electrophoresis and MALDI mass spectrometry. 25809283 1 28 theme key 247:249 arg1 importance 251:260 key importance 247:260 key importance 247:260 The human immunodeficiency virus (HIV) envelope glycoprotein (Env) is the primary antigenic feature on the surface of the virus and is of key importance in HIV vaccinology. 25809283 1 29 from importance 251:260 arg1 surface 216:222 the surface 212:222 the surface of the virus 212:235 The human immunodeficiency virus (HIV) envelope glycoprotein (Env) is the primary antigenic feature on the surface of the virus and is of key importance in HIV vaccinology. 25809283 1 29 from importance 251:260 arg1 vaccinology 269:279 HIV vaccinology 265:279 HIV vaccinology 265:279 The human immunodeficiency virus (HIV) envelope glycoprotein (Env) is the primary antigenic feature on the surface of the virus and is of key importance in HIV vaccinology. 25809283 2 30 theme Vaccine 282:288 arg1 trials 290:295 Vaccine trials 282:295 Vaccine trials with the gp120 subunit of Env 282:325 Vaccine trials with the gp120 subunit of Env are ongoing, with the recent RV144 trial showing moderate efficacy. 25809283 4 31 theme several 611:617 arg1 gp120s 619:624 several gp120s 611:624 several gp120s 611:624 To assess how the global glycosylation patterns vary between gp120 constructs, the glycan profiles of several gp120s were examined by CE with LIF detection and MALDI-MS. 25809283 0 32 theme HIV 30:32 arg1 gp120 34:38 HIV gp120 30:38 HIV gp120 30:38 Comparative glycoprofiling of HIV gp120 immunogens by capillary electrophoresis and MALDI mass spectrometry. 25809283 6 33 theme herpes 912:917 arg1 virus 927:931 the herpes simplex virus 908:931 the herpes simplex virus glycoprotein D tag used in the RV144 trial 908:974 This study revealed that the addition of specific tags, such as the herpes simplex virus glycoprotein D tag used in the RV144 trial, had significant effects on the overall glycosylation patterns. 25809283 1 34 theme primary 183:189 arg1 glycoprotein 157:168 The human immunodeficiency virus (HIV) envelope glycoprotein 109:168 The human immunodeficiency virus (HIV) envelope glycoprotein (Env) 109:174 The human immunodeficiency virus (HIV) envelope glycoprotein (Env) is the primary antigenic feature on the surface of the virus and is of key importance in HIV vaccinology. 25809283 1 34 theme primary 183:189 arg1 feature 201:207 the primary antigenic feature 179:207 the primary antigenic feature on the surface of the virus 179:235 The human immunodeficiency virus (HIV) envelope glycoprotein (Env) is the primary antigenic feature on the surface of the virus and is of key importance in HIV vaccinology. 25809283 5 35 from clades 836:841 arg1 gp120s 814:819 gp120s 814:819 gp120s from different clades 814:841 The glycosylation profiles were found to be similar for chronic versus transmitter/founder isolates and only varied moderately between gp120s from different clades. 25809283 1 36 theme human 113:117 arg1 HIV 143:145 HIV 143:145 HIV 143:145 The human immunodeficiency virus (HIV) envelope glycoprotein (Env) is the primary antigenic feature on the surface of the virus and is of key importance in HIV vaccinology. 25809283 1 36 theme human 113:117 arg1 virus 136:140 human immunodeficiency virus 113:140 The human immunodeficiency virus (HIV) envelope glycoprotein (Env) 109:174 The human immunodeficiency virus (HIV) envelope glycoprotein (Env) is the primary antigenic feature on the surface of the virus and is of key importance in HIV vaccinology. 25809283 1 37 theme antigenic 191:199 arg1 glycoprotein 157:168 The human immunodeficiency virus (HIV) envelope glycoprotein 109:168 The human immunodeficiency virus (HIV) envelope glycoprotein (Env) 109:174 The human immunodeficiency virus (HIV) envelope glycoprotein (Env) is the primary antigenic feature on the surface of the virus and is of key importance in HIV vaccinology. 25809283 1 37 theme antigenic 191:199 arg1 feature 201:207 the primary antigenic feature 179:207 the primary antigenic feature on the surface of the virus 179:235 The human immunodeficiency virus (HIV) envelope glycoprotein (Env) is the primary antigenic feature on the surface of the virus and is of key importance in HIV vaccinology. 25809283 7 38 theme vaccine 1158:1164 arg1 strategies 1166:1175 future vaccine strategies 1151:1175 future vaccine strategies 1151:1175 Such effects are likely to influence the immunogenicity of various Env immunogens and should be considered for future vaccine strategies, emphasizing the importance of the glycosylation analysis approach described in this paper. 25809283 2 39 theme gp120 306:310 arg1 subunit 312:318 the gp120 subunit 302:318 the gp120 subunit of Env 302:325 Vaccine trials with the gp120 subunit of Env are ongoing, with the recent RV144 trial showing moderate efficacy. 25809283 4 40 theme glycan 592:597 arg1 profiles 599:606 the glycan profiles 588:606 the glycan profiles of several gp120s 588:624 To assess how the global glycosylation patterns vary between gp120 constructs, the glycan profiles of several gp120s were examined by CE with LIF detection and MALDI-MS. 25809283 0 41 theme gp120 34:38 arg1 glycoprofiling 12:25 Comparative glycoprofiling 0:25 Comparative glycoprofiling of HIV gp120 0:38 Comparative glycoprofiling of HIV gp120 immunogens by capillary electrophoresis and MALDI mass spectrometry. 25809283 7 42 theme various 1099:1105 arg1 immunogens 1111:1120 various Env immunogens 1099:1120 various Env immunogens 1099:1120 Such effects are likely to influence the immunogenicity of various Env immunogens and should be considered for future vaccine strategies, emphasizing the importance of the glycosylation analysis approach described in this paper. 25809283 1 43 from feature 201:207 arg1 surface 216:222 the surface 212:222 the surface of the virus 212:235 The human immunodeficiency virus (HIV) envelope glycoprotein (Env) is the primary antigenic feature on the surface of the virus and is of key importance in HIV vaccinology. 25809283 1 43 from feature 201:207 arg1 vaccinology 269:279 HIV vaccinology 265:279 HIV vaccinology 265:279 The human immunodeficiency virus (HIV) envelope glycoprotein (Env) is the primary antigenic feature on the surface of the virus and is of key importance in HIV vaccinology. 25809283 2 44 theme RV144 356:360 arg1 trial 362:366 the recent RV144 trial 345:366 the recent RV144 trial showing moderate efficacy 345:392 Vaccine trials with the gp120 subunit of Env are ongoing, with the recent RV144 trial showing moderate efficacy. 25809283 0 45 theme capillary 54:62 arg1 electrophoresis 64:78 capillary electrophoresis 54:78 capillary electrophoresis 54:78 Comparative glycoprofiling of HIV gp120 immunogens by capillary electrophoresis and MALDI mass spectrometry. 25809283 1 46 theme immunodeficiency 119:134 arg1 HIV 143:145 HIV 143:145 HIV 143:145 The human immunodeficiency virus (HIV) envelope glycoprotein (Env) is the primary antigenic feature on the surface of the virus and is of key importance in HIV vaccinology. 25809283 1 46 theme immunodeficiency 119:134 arg1 virus 136:140 human immunodeficiency virus 113:140 The human immunodeficiency virus (HIV) envelope glycoprotein (Env) 109:174 The human immunodeficiency virus (HIV) envelope glycoprotein (Env) is the primary antigenic feature on the surface of the virus and is of key importance in HIV vaccinology. 25809283 5 47 theme chronic 735:741 arg1 isolates 770:777 chronic versus transmitter/founder isolates 735:777 chronic versus transmitter/founder isolates 735:777 The glycosylation profiles were found to be similar for chronic versus transmitter/founder isolates and only varied moderately between gp120s from different clades. 25809283 6 48 theme tags 894:897 arg1 addition 873:880 the addition 869:880 the addition of specific tags, such as the herpes simplex virus glycoprotein D tag used in the RV144 trial, 869:975 This study revealed that the addition of specific tags, such as the herpes simplex virus glycoprotein D tag used in the RV144 trial, had significant effects on the overall glycosylation patterns. 25809283 7 49 theme analysis 1226:1233 arg1 approach 1235:1242 the glycosylation analysis approach 1208:1242 the glycosylation analysis approach described in this paper 1208:1266 Such effects are likely to influence the immunogenicity of various Env immunogens and should be considered for future vaccine strategies, emphasizing the importance of the glycosylation analysis approach described in this paper. 25809283 1 50 theme virus 136:140 arg1 feature 201:207 the primary antigenic feature 179:207 the primary antigenic feature on the surface of the virus 179:235 The human immunodeficiency virus (HIV) envelope glycoprotein (Env) is the primary antigenic feature on the surface of the virus and is of key importance in HIV vaccinology. 25809283 1 50 theme virus 136:140 arg1 Env 171:173 Env 171:173 Env 171:173 The human immunodeficiency virus (HIV) envelope glycoprotein (Env) is the primary antigenic feature on the surface of the virus and is of key importance in HIV vaccinology. 25809283 1 50 theme virus 136:140 arg1 glycoprotein 157:168 The human immunodeficiency virus (HIV) envelope glycoprotein 109:168 The human immunodeficiency virus (HIV) envelope glycoprotein (Env) 109:174 The human immunodeficiency virus (HIV) envelope glycoprotein (Env) is the primary antigenic feature on the surface of the virus and is of key importance in HIV vaccinology. 25809283 6 51 theme specific 885:892 arg1 tag 948:950 the herpes simplex virus glycoprotein D tag 908:950 the herpes simplex virus glycoprotein D tag used in the RV144 trial 908:974 This study revealed that the addition of specific tags, such as the herpes simplex virus glycoprotein D tag used in the RV144 trial, had significant effects on the overall glycosylation patterns. 25809283 6 51 theme specific 885:892 arg1 tags 894:897 specific tags 885:897 specific tags 885:897 This study revealed that the addition of specific tags, such as the herpes simplex virus glycoprotein D tag used in the RV144 trial, had significant effects on the overall glycosylation patterns. 25809283 6 52 gly glycoprotein 933:944 arg1 glycoprotein 933:944 the herpes simplex virus glycoprotein D tag 908:950 the herpes simplex virus glycoprotein D tag used in the RV144 trial 908:974 This study revealed that the addition of specific tags, such as the herpes simplex virus glycoprotein D tag used in the RV144 trial, had significant effects on the overall glycosylation patterns. 25809283 6 53 theme glycoprotein 933:944 arg1 tag 948:950 the herpes simplex virus glycoprotein D tag 908:950 the herpes simplex virus glycoprotein D tag used in the RV144 trial 908:974 This study revealed that the addition of specific tags, such as the herpes simplex virus glycoprotein D tag used in the RV144 trial, had significant effects on the overall glycosylation patterns. 25809283 1 54 gly glycoprotein 157:168 arg1 feature 201:207 the primary antigenic feature 179:207 the primary antigenic feature on the surface of the virus 179:235 The human immunodeficiency virus (HIV) envelope glycoprotein (Env) is the primary antigenic feature on the surface of the virus and is of key importance in HIV vaccinology. 25809283 1 54 gly glycoprotein 157:168 arg1 Env 171:173 Env 171:173 Env 171:173 The human immunodeficiency virus (HIV) envelope glycoprotein (Env) is the primary antigenic feature on the surface of the virus and is of key importance in HIV vaccinology. 25809283 1 54 gly glycoprotein 157:168 arg1 glycoprotein 157:168 The human immunodeficiency virus (HIV) envelope glycoprotein 109:168 The human immunodeficiency virus (HIV) envelope glycoprotein (Env) 109:174 The human immunodeficiency virus (HIV) envelope glycoprotein (Env) is the primary antigenic feature on the surface of the virus and is of key importance in HIV vaccinology. 25809283 2 55 with ongoing 331:337 arg1 trial 362:366 the recent RV144 trial 345:366 the recent RV144 trial showing moderate efficacy 345:392 Vaccine trials with the gp120 subunit of Env are ongoing, with the recent RV144 trial showing moderate efficacy. 25809283 6 56 theme significant 981:991 arg1 effects 993:999 significant effects 981:999 significant effects 981:999 This study revealed that the addition of specific tags, such as the herpes simplex virus glycoprotein D tag used in the RV144 trial, had significant effects on the overall glycosylation patterns. 25809283 7 57 theme glycosylation 1212:1224 arg1 approach 1235:1242 the glycosylation analysis approach 1208:1242 the glycosylation analysis approach described in this paper 1208:1266 Such effects are likely to influence the immunogenicity of various Env immunogens and should be considered for future vaccine strategies, emphasizing the importance of the glycosylation analysis approach described in this paper. 25809283 2 58 theme moderate 376:383 arg1 efficacy 385:392 moderate efficacy 376:392 moderate efficacy 376:392 Vaccine trials with the gp120 subunit of Env are ongoing, with the recent RV144 trial showing moderate efficacy. 25809283 4 59 theme gp120 570:574 arg1 constructs 576:585 gp120 constructs 570:585 gp120 constructs 570:585 To assess how the global glycosylation patterns vary between gp120 constructs, the glycan profiles of several gp120s were examined by CE with LIF detection and MALDI-MS. 25809283 4 60 theme glycosylation 534:546 arg1 patterns 548:555 the global glycosylation patterns 523:555 the global glycosylation patterns 523:555 To assess how the global glycosylation patterns vary between gp120 constructs, the glycan profiles of several gp120s were examined by CE with LIF detection and MALDI-MS. 25809283 7 61 theme Env 1107:1109 arg1 immunogens 1111:1120 various Env immunogens 1099:1120 various Env immunogens 1099:1120 Such effects are likely to influence the immunogenicity of various Env immunogens and should be considered for future vaccine strategies, emphasizing the importance of the glycosylation analysis approach described in this paper. 25809283 1 62 theme envelope 148:155 arg1 feature 201:207 the primary antigenic feature 179:207 the primary antigenic feature on the surface of the virus 179:235 The human immunodeficiency virus (HIV) envelope glycoprotein (Env) is the primary antigenic feature on the surface of the virus and is of key importance in HIV vaccinology. 25809283 1 62 theme envelope 148:155 arg1 Env 171:173 Env 171:173 Env 171:173 The human immunodeficiency virus (HIV) envelope glycoprotein (Env) is the primary antigenic feature on the surface of the virus and is of key importance in HIV vaccinology. 25809283 1 62 theme envelope 148:155 arg1 glycoprotein 157:168 The human immunodeficiency virus (HIV) envelope glycoprotein 109:168 The human immunodeficiency virus (HIV) envelope glycoprotein (Env) 109:174 The human immunodeficiency virus (HIV) envelope glycoprotein (Env) is the primary antigenic feature on the surface of the virus and is of key importance in HIV vaccinology. 25809283 7 63 theme approach 1235:1242 arg1 importance 1194:1203 the importance 1190:1203 the importance of the glycosylation analysis approach described in this paper 1190:1266 Such effects are likely to influence the immunogenicity of various Env immunogens and should be considered for future vaccine strategies, emphasizing the importance of the glycosylation analysis approach described in this paper. 25299151 7 0 theme interaction 1349:1359 arg1 chromatography 1368:1381 hydrophilic interaction liquid chromatography 1337:1381 hydrophilic interaction liquid chromatography 1337:1381 The LC method is capable of separating sialylated N-glycan isomers differing in α2-3 and α2-6 linkages using a novel superficially porous particle (Fused-Core) Penta-HILIC (hydrophilic interaction liquid chromatography) column. 25299151 4 1 theme important 710:718 arg1 role 720:723 an important role 707:723 an important role 707:723 For instance, previous studies have shown that the ratio of α2-3 to α2-6 linked sialic acid (SA) plays an important role in cancer biology. 25299151 1 2 theme N-linked 159:166 arg1 glycans 168:174 N-linked glycans 159:174 N-linked glycans 159:174 The study of N-linked glycans is among the most challenging bioanalytical tasks because of their complexity and variety. 25299151 5 3 theme quantitative 758:769 arg1 methods 771:777 quantitative methods 758:777 quantitative methods to detect alterations in the ratios of glycans based on their SA linkages 758:851 Consequently, quantitative methods to detect alterations in the ratios of glycans based on their SA linkages could serve as a diagnostic tool in oncology, yet traditional glycomic profiling cannot readily differentiate between these linkage isomers. 25299151 5 3 theme quantitative 758:769 arg1 tool 881:884 a diagnostic tool 868:884 a diagnostic tool in oncology 868:896 Consequently, quantitative methods to detect alterations in the ratios of glycans based on their SA linkages could serve as a diagnostic tool in oncology, yet traditional glycomic profiling cannot readily differentiate between these linkage isomers. 25299151 1 4 theme glycans 168:174 arg1 study 150:154 The study 146:154 The study of N-linked glycans 146:174 The study of N-linked glycans is among the most challenging bioanalytical tasks because of their complexity and variety. 25299151 4 5 theme previous 618:625 arg1 studies 627:633 previous studies 618:633 previous studies 618:633 For instance, previous studies have shown that the ratio of α2-3 to α2-6 linked sialic acid (SA) plays an important role in cancer biology. 25299151 8 6 theme linkage 1452:1458 arg1 isomer 1460:1465 each SA linkage isomer 1444:1465 each SA linkage isomer 1444:1465 SRM detection provides the relative quantitation of each SA linkage isomer, and minimizes interferences from coeluting glycans that are problematic for UV/Fluorescence based quantitation. 25299151 7 7 theme Penta-HILIC 1324:1334 arg1 column 1384:1389 a novel superficially porous particle (Fused-Core) Penta-HILIC (hydrophilic interaction liquid chromatography) column 1273:1389 a novel superficially porous particle (Fused-Core) Penta-HILIC (hydrophilic interaction liquid chromatography) column 1273:1389 The LC method is capable of separating sialylated N-glycan isomers differing in α2-3 and α2-6 linkages using a novel superficially porous particle (Fused-Core) Penta-HILIC (hydrophilic interaction liquid chromatography) column. 25299151 2 8 dep identification 366:379 arg1 the 362:364 the 362:364 the 362:364 The presence of glycoform families that differ only in branching and/or linkage position makes the identification and quantitation of individual glycans exceedingly difficult. 25299151 9 9 theme linkage 1636:1642 arg1 isomer 1644:1649 each SA linkage isomer 1628:1649 each SA linkage isomer 1628:1649 With our approach, the relative quantitation of each SA linkage isomer is obtained from a straightforward liquid chromatography-mass spectrometry (LC-MS) experiment. 25299151 7 10 theme N-glycan 1214:1221 arg1 isomers 1223:1229 sialylated N-glycan isomers 1203:1229 sialylated N-glycan isomers differing in α2-3 and α2-6 linkages using a novel superficially porous particle (Fused-Core) Penta-HILIC (hydrophilic interaction liquid chromatography) column 1203:1389 The LC method is capable of separating sialylated N-glycan isomers differing in α2-3 and α2-6 linkages using a novel superficially porous particle (Fused-Core) Penta-HILIC (hydrophilic interaction liquid chromatography) column. 25299151 9 11 theme SA 1633:1634 arg1 isomer 1644:1649 each SA linkage isomer 1628:1649 each SA linkage isomer 1628:1649 With our approach, the relative quantitation of each SA linkage isomer is obtained from a straightforward liquid chromatography-mass spectrometry (LC-MS) experiment. 25299151 2 12 theme families 293:300 arg1 presence 271:278 The presence 267:278 The presence of glycoform families that differ only in branching and/or linkage position 267:354 The presence of glycoform families that differ only in branching and/or linkage position makes the identification and quantitation of individual glycans exceedingly difficult. 25299151 3 13 theme isomers 539:545 arg1 abundance 520:528 the abundance 516:528 the abundance of these isomers 516:545 Quantitation of these individual glycans is important because changes in the abundance of these isomers are often associated with significant biomedical events. 25299151 6 14 theme individual 1133:1142 arg1 isomers 1155:1161 the individual SA linkage isomers 1129:1161 the individual SA linkage isomers 1129:1161 Here, we present a liquid chromatography-selected reaction monitoring (LC-SRM) approach that we demonstrate is capable of quantitating the individual SA linkage isomers. 25299151 0 15 theme N-glycans 119:127 arg1 isomers 137:143 sialylated N-glycans linkage isomers 108:143 sialylated N-glycans linkage isomers 108:143 Liquid chromatography-selected reaction monitoring (LC-SRM) approach for the separation and quantitation of sialylated N-glycans linkage isomers. 25299151 4 16 theme α2-3 664:667 arg1 ratio 655:659 the ratio 651:659 the ratio of α2-3 to α2-6 linked sialic acid (SA) 651:699 For instance, previous studies have shown that the ratio of α2-3 to α2-6 linked sialic acid (SA) plays an important role in cancer biology. 25299151 2 17 theme glycoform 283:291 arg1 families 293:300 glycoform families 283:300 glycoform families that differ only in branching and/or linkage position 283:354 The presence of glycoform families that differ only in branching and/or linkage position makes the identification and quantitation of individual glycans exceedingly difficult. 25299151 5 18 theme diagnostic 870:879 arg1 methods 771:777 quantitative methods 758:777 quantitative methods to detect alterations in the ratios of glycans based on their SA linkages 758:851 Consequently, quantitative methods to detect alterations in the ratios of glycans based on their SA linkages could serve as a diagnostic tool in oncology, yet traditional glycomic profiling cannot readily differentiate between these linkage isomers. 25299151 5 18 theme diagnostic 870:879 arg1 tool 881:884 a diagnostic tool 868:884 a diagnostic tool in oncology 868:896 Consequently, quantitative methods to detect alterations in the ratios of glycans based on their SA linkages could serve as a diagnostic tool in oncology, yet traditional glycomic profiling cannot readily differentiate between these linkage isomers. 25299151 3 19 theme glycans 476:482 arg1 Quantitation 443:454 Quantitation 443:454 Quantitation of these individual glycans 443:482 Quantitation of these individual glycans is important because changes in the abundance of these isomers are often associated with significant biomedical events. 25299151 0 20 theme sialylated 108:117 arg1 isomers 137:143 sialylated N-glycans linkage isomers 108:143 sialylated N-glycans linkage isomers 108:143 Liquid chromatography-selected reaction monitoring (LC-SRM) approach for the separation and quantitation of sialylated N-glycans linkage isomers. 25299151 6 21 theme SA 1144:1145 arg1 isomers 1155:1161 the individual SA linkage isomers 1129:1161 the individual SA linkage isomers 1129:1161 Here, we present a liquid chromatography-selected reaction monitoring (LC-SRM) approach that we demonstrate is capable of quantitating the individual SA linkage isomers. 25299151 3 22 theme significant 573:583 arg1 events 596:601 significant biomedical events 573:601 significant biomedical events 573:601 Quantitation of these individual glycans is important because changes in the abundance of these isomers are often associated with significant biomedical events. 25299151 2 23 theme glycans 412:418 arg1 identification 366:379 identification 366:379 identification 366:379 The presence of glycoform families that differ only in branching and/or linkage position makes the identification and quantitation of individual glycans exceedingly difficult. 25299151 2 23 theme glycans 412:418 arg1 quantitation 385:396 quantitation 385:396 quantitation 385:396 The presence of glycoform families that differ only in branching and/or linkage position makes the identification and quantitation of individual glycans exceedingly difficult. 25299151 0 24 theme chromatography-selected 7:29 arg1 LC-SRM 52:57 LC-SRM 52:57 LC-SRM 52:57 Liquid chromatography-selected reaction monitoring (LC-SRM) approach for the separation and quantitation of sialylated N-glycans linkage isomers. 25299151 0 24 theme chromatography-selected 7:29 arg1 monitoring 40:49 Liquid chromatography-selected reaction monitoring 0:49 Liquid chromatography-selected reaction monitoring (LC-SRM) 0:58 Liquid chromatography-selected reaction monitoring (LC-SRM) approach for the separation and quantitation of sialylated N-glycans linkage isomers. 25299151 2 25 theme individual 401:410 arg1 glycans 412:418 individual glycans 401:418 individual glycans 401:418 The presence of glycoform families that differ only in branching and/or linkage position makes the identification and quantitation of individual glycans exceedingly difficult. 25299151 0 26 theme Liquid 0:5 arg1 LC-SRM 52:57 LC-SRM 52:57 LC-SRM 52:57 Liquid chromatography-selected reaction monitoring (LC-SRM) approach for the separation and quantitation of sialylated N-glycans linkage isomers. 25299151 0 26 theme Liquid 0:5 arg1 monitoring 40:49 Liquid chromatography-selected reaction monitoring 0:49 Liquid chromatography-selected reaction monitoring (LC-SRM) 0:58 Liquid chromatography-selected reaction monitoring (LC-SRM) approach for the separation and quantitation of sialylated N-glycans linkage isomers. 25299151 9 27 theme straightforward 1670:1684 arg1 experiment 1734:1743 a straightforward liquid chromatography-mass spectrometry (LC-MS) experiment 1668:1743 a straightforward liquid chromatography-mass spectrometry (LC-MS) experiment 1668:1743 With our approach, the relative quantitation of each SA linkage isomer is obtained from a straightforward liquid chromatography-mass spectrometry (LC-MS) experiment. 25299151 0 28 dep separation 77:86 arg1 the 73:75 the 73:75 the 73:75 Liquid chromatography-selected reaction monitoring (LC-SRM) approach for the separation and quantitation of sialylated N-glycans linkage isomers. 25299151 8 29 theme SRM 1392:1394 arg1 detection 1396:1404 SRM detection 1392:1404 SRM detection 1392:1404 SRM detection provides the relative quantitation of each SA linkage isomer, and minimizes interferences from coeluting glycans that are problematic for UV/Fluorescence based quantitation. 25299151 1 30 theme most 189:192 arg1 tasks 220:224 the most challenging bioanalytical tasks 185:224 the most challenging bioanalytical tasks 185:224 The study of N-linked glycans is among the most challenging bioanalytical tasks because of their complexity and variety. 25299151 9 31 theme liquid 1686:1691 arg1 LC-MS 1727:1731 LC-MS 1727:1731 LC-MS 1727:1731 With our approach, the relative quantitation of each SA linkage isomer is obtained from a straightforward liquid chromatography-mass spectrometry (LC-MS) experiment. 25299151 9 31 theme liquid 1686:1691 arg1 spectrometry 1713:1724 liquid chromatography-mass spectrometry 1686:1724 a straightforward liquid chromatography-mass spectrometry (LC-MS) experiment 1668:1743 With our approach, the relative quantitation of each SA linkage isomer is obtained from a straightforward liquid chromatography-mass spectrometry (LC-MS) experiment. 25299151 0 32 theme isomers 137:143 arg1 separation 77:86 separation 77:86 separation 77:86 Liquid chromatography-selected reaction monitoring (LC-SRM) approach for the separation and quantitation of sialylated N-glycans linkage isomers. 25299151 0 32 theme isomers 137:143 arg1 quantitation 92:103 quantitation 92:103 quantitation 92:103 Liquid chromatography-selected reaction monitoring (LC-SRM) approach for the separation and quantitation of sialylated N-glycans linkage isomers. 25299151 0 33 gly sialylated 108:117 arg1 isomers 137:143 sialylated N-glycans linkage isomers 108:143 sialylated N-glycans linkage isomers 108:143 Liquid chromatography-selected reaction monitoring (LC-SRM) approach for the separation and quantitation of sialylated N-glycans linkage isomers. 25299151 8 34 theme UV/Fluorescence 1544:1558 arg1 quantitation 1566:1577 UV/Fluorescence based quantitation 1544:1577 UV/Fluorescence based quantitation 1544:1577 SRM detection provides the relative quantitation of each SA linkage isomer, and minimizes interferences from coeluting glycans that are problematic for UV/Fluorescence based quantitation. 25299151 1 35 theme challenging 194:204 arg1 tasks 220:224 the most challenging bioanalytical tasks 185:224 the most challenging bioanalytical tasks 185:224 The study of N-linked glycans is among the most challenging bioanalytical tasks because of their complexity and variety. 25299151 0 36 theme reaction 31:38 arg1 LC-SRM 52:57 LC-SRM 52:57 LC-SRM 52:57 Liquid chromatography-selected reaction monitoring (LC-SRM) approach for the separation and quantitation of sialylated N-glycans linkage isomers. 25299151 0 36 theme reaction 31:38 arg1 monitoring 40:49 Liquid chromatography-selected reaction monitoring 0:49 Liquid chromatography-selected reaction monitoring (LC-SRM) 0:58 Liquid chromatography-selected reaction monitoring (LC-SRM) approach for the separation and quantitation of sialylated N-glycans linkage isomers. 25299151 0 37 theme linkage 129:135 arg1 isomers 137:143 sialylated N-glycans linkage isomers 108:143 sialylated N-glycans linkage isomers 108:143 Liquid chromatography-selected reaction monitoring (LC-SRM) approach for the separation and quantitation of sialylated N-glycans linkage isomers. 25299151 7 38 theme hydrophilic 1337:1347 arg1 chromatography 1368:1381 hydrophilic interaction liquid chromatography 1337:1381 hydrophilic interaction liquid chromatography 1337:1381 The LC method is capable of separating sialylated N-glycan isomers differing in α2-3 and α2-6 linkages using a novel superficially porous particle (Fused-Core) Penta-HILIC (hydrophilic interaction liquid chromatography) column. 25299151 1 39 theme bioanalytical 206:218 arg1 tasks 220:224 the most challenging bioanalytical tasks 185:224 the most challenging bioanalytical tasks 185:224 The study of N-linked glycans is among the most challenging bioanalytical tasks because of their complexity and variety. 25299151 7 40 theme LC 1168:1169 arg1 capable 1181:1187 capable 1181:1187 capable 1181:1187 The LC method is capable of separating sialylated N-glycan isomers differing in α2-3 and α2-6 linkages using a novel superficially porous particle (Fused-Core) Penta-HILIC (hydrophilic interaction liquid chromatography) column. 25299151 7 40 theme LC 1168:1169 arg1 method 1171:1176 The LC method 1164:1176 The LC method 1164:1176 The LC method is capable of separating sialylated N-glycan isomers differing in α2-3 and α2-6 linkages using a novel superficially porous particle (Fused-Core) Penta-HILIC (hydrophilic interaction liquid chromatography) column. 25299151 5 41 theme linkage 977:983 arg1 isomers 985:991 these linkage isomers 971:991 these linkage isomers 971:991 Consequently, quantitative methods to detect alterations in the ratios of glycans based on their SA linkages could serve as a diagnostic tool in oncology, yet traditional glycomic profiling cannot readily differentiate between these linkage isomers. 25299151 5 42 dep methods 771:777 arg1 detect 782:787 detect 782:787 to detect alterations in the ratios of glycans based on their SA linkages 779:851 Consequently, quantitative methods to detect alterations in the ratios of glycans based on their SA linkages could serve as a diagnostic tool in oncology, yet traditional glycomic profiling cannot readily differentiate between these linkage isomers. 25299151 6 43 theme linkage 1147:1153 arg1 isomers 1155:1161 the individual SA linkage isomers 1129:1161 the individual SA linkage isomers 1129:1161 Here, we present a liquid chromatography-selected reaction monitoring (LC-SRM) approach that we demonstrate is capable of quantitating the individual SA linkage isomers. 25299151 9 44 theme isomer 1644:1649 arg1 quantitation 1612:1623 the relative quantitation 1599:1623 the relative quantitation of each SA linkage isomer 1599:1649 With our approach, the relative quantitation of each SA linkage isomer is obtained from a straightforward liquid chromatography-mass spectrometry (LC-MS) experiment. 25299151 3 45 theme individual 465:474 arg1 glycans 476:482 these individual glycans 459:482 these individual glycans 459:482 Quantitation of these individual glycans is important because changes in the abundance of these isomers are often associated with significant biomedical events. 25299151 4 46 theme linked 677:682 arg1 acid 691:694 α2-6 linked sialic acid 672:694 α2-6 linked sialic acid (SA) 672:699 For instance, previous studies have shown that the ratio of α2-3 to α2-6 linked sialic acid (SA) plays an important role in cancer biology. 25299151 4 46 theme linked 677:682 arg1 SA 697:698 SA 697:698 SA 697:698 For instance, previous studies have shown that the ratio of α2-3 to α2-6 linked sialic acid (SA) plays an important role in cancer biology. 25299151 7 47 theme liquid 1361:1366 arg1 chromatography 1368:1381 hydrophilic interaction liquid chromatography 1337:1381 hydrophilic interaction liquid chromatography 1337:1381 The LC method is capable of separating sialylated N-glycan isomers differing in α2-3 and α2-6 linkages using a novel superficially porous particle (Fused-Core) Penta-HILIC (hydrophilic interaction liquid chromatography) column. 25299151 9 48 theme spectrometry 1713:1724 arg1 experiment 1734:1743 a straightforward liquid chromatography-mass spectrometry (LC-MS) experiment 1668:1743 a straightforward liquid chromatography-mass spectrometry (LC-MS) experiment 1668:1743 With our approach, the relative quantitation of each SA linkage isomer is obtained from a straightforward liquid chromatography-mass spectrometry (LC-MS) experiment. 25299151 4 49 theme α2-6 672:675 arg1 acid 691:694 α2-6 linked sialic acid 672:694 α2-6 linked sialic acid (SA) 672:699 For instance, previous studies have shown that the ratio of α2-3 to α2-6 linked sialic acid (SA) plays an important role in cancer biology. 25299151 4 49 theme α2-6 672:675 arg1 SA 697:698 SA 697:698 SA 697:698 For instance, previous studies have shown that the ratio of α2-3 to α2-6 linked sialic acid (SA) plays an important role in cancer biology. 25299151 5 50 from tool 881:884 arg1 oncology 889:896 oncology 889:896 oncology 889:896 Consequently, quantitative methods to detect alterations in the ratios of glycans based on their SA linkages could serve as a diagnostic tool in oncology, yet traditional glycomic profiling cannot readily differentiate between these linkage isomers. 25299151 8 51 theme SA 1449:1450 arg1 isomer 1460:1465 each SA linkage isomer 1444:1465 each SA linkage isomer 1444:1465 SRM detection provides the relative quantitation of each SA linkage isomer, and minimizes interferences from coeluting glycans that are problematic for UV/Fluorescence based quantitation. 25299151 5 52 theme traditional 903:913 arg1 profiling 924:932 traditional glycomic profiling 903:932 traditional glycomic profiling 903:932 Consequently, quantitative methods to detect alterations in the ratios of glycans based on their SA linkages could serve as a diagnostic tool in oncology, yet traditional glycomic profiling cannot readily differentiate between these linkage isomers. 25299151 8 53 theme based 1560:1564 arg1 quantitation 1566:1577 UV/Fluorescence based quantitation 1544:1577 UV/Fluorescence based quantitation 1544:1577 SRM detection provides the relative quantitation of each SA linkage isomer, and minimizes interferences from coeluting glycans that are problematic for UV/Fluorescence based quantitation. 25299151 1 54 link N-linked 159:166 arg1 glycans 168:174 N-linked glycans 159:174 N-linked glycans 159:174 The study of N-linked glycans is among the most challenging bioanalytical tasks because of their complexity and variety. 25299151 3 55 from changes 505:511 arg1 abundance 520:528 the abundance 516:528 the abundance of these isomers 516:545 Quantitation of these individual glycans is important because changes in the abundance of these isomers are often associated with significant biomedical events. 25299151 5 56 theme glycomic 915:922 arg1 profiling 924:932 traditional glycomic profiling 903:932 traditional glycomic profiling 903:932 Consequently, quantitative methods to detect alterations in the ratios of glycans based on their SA linkages could serve as a diagnostic tool in oncology, yet traditional glycomic profiling cannot readily differentiate between these linkage isomers. 25299151 8 57 theme isomer 1460:1465 arg1 quantitation 1428:1439 the relative quantitation 1415:1439 the relative quantitation of each SA linkage isomer 1415:1465 SRM detection provides the relative quantitation of each SA linkage isomer, and minimizes interferences from coeluting glycans that are problematic for UV/Fluorescence based quantitation. 25299151 7 58 theme novel 1275:1279 arg1 column 1384:1389 a novel superficially porous particle (Fused-Core) Penta-HILIC (hydrophilic interaction liquid chromatography) column 1273:1389 a novel superficially porous particle (Fused-Core) Penta-HILIC (hydrophilic interaction liquid chromatography) column 1273:1389 The LC method is capable of separating sialylated N-glycan isomers differing in α2-3 and α2-6 linkages using a novel superficially porous particle (Fused-Core) Penta-HILIC (hydrophilic interaction liquid chromatography) column. 25299151 5 59 from alterations 789:799 arg1 ratios 808:813 the ratios 804:813 the ratios of glycans based on their SA linkages 804:851 Consequently, quantitative methods to detect alterations in the ratios of glycans based on their SA linkages could serve as a diagnostic tool in oncology, yet traditional glycomic profiling cannot readily differentiate between these linkage isomers. 25299151 4 60 link linked 677:682 arg1 acid 691:694 α2-6 linked sialic acid 672:694 α2-6 linked sialic acid (SA) 672:699 For instance, previous studies have shown that the ratio of α2-3 to α2-6 linked sialic acid (SA) plays an important role in cancer biology. 25299151 4 60 link linked 677:682 arg1 SA 697:698 SA 697:698 SA 697:698 For instance, previous studies have shown that the ratio of α2-3 to α2-6 linked sialic acid (SA) plays an important role in cancer biology. 25299151 2 61 theme linkage 339:345 arg1 position 347:354 linkage position 339:354 linkage position 339:354 The presence of glycoform families that differ only in branching and/or linkage position makes the identification and quantitation of individual glycans exceedingly difficult. 25299151 8 62 theme relative 1419:1426 arg1 quantitation 1428:1439 the relative quantitation 1415:1439 the relative quantitation of each SA linkage isomer 1415:1465 SRM detection provides the relative quantitation of each SA linkage isomer, and minimizes interferences from coeluting glycans that are problematic for UV/Fluorescence based quantitation. 25299151 6 63 theme monitoring 1053:1062 arg1 approach 1073:1080 a liquid chromatography-selected reaction monitoring (LC-SRM) approach 1011:1080 a liquid chromatography-selected reaction monitoring (LC-SRM) approach that we demonstrate is capable of quantitating the individual SA linkage isomers 1011:1161 Here, we present a liquid chromatography-selected reaction monitoring (LC-SRM) approach that we demonstrate is capable of quantitating the individual SA linkage isomers. 25299151 7 64 gly sialylated 1203:1212 arg1 isomers 1223:1229 sialylated N-glycan isomers 1203:1229 sialylated N-glycan isomers differing in α2-3 and α2-6 linkages using a novel superficially porous particle (Fused-Core) Penta-HILIC (hydrophilic interaction liquid chromatography) column 1203:1389 The LC method is capable of separating sialylated N-glycan isomers differing in α2-3 and α2-6 linkages using a novel superficially porous particle (Fused-Core) Penta-HILIC (hydrophilic interaction liquid chromatography) column. 25299151 3 65 theme biomedical 585:594 arg1 events 596:601 significant biomedical events 573:601 significant biomedical events 573:601 Quantitation of these individual glycans is important because changes in the abundance of these isomers are often associated with significant biomedical events. 25299151 4 66 theme cancer 728:733 arg1 biology 735:741 cancer biology 728:741 cancer biology 728:741 For instance, previous studies have shown that the ratio of α2-3 to α2-6 linked sialic acid (SA) plays an important role in cancer biology. 25299151 6 67 theme reaction 1044:1051 arg1 LC-SRM 1065:1070 LC-SRM 1065:1070 LC-SRM 1065:1070 Here, we present a liquid chromatography-selected reaction monitoring (LC-SRM) approach that we demonstrate is capable of quantitating the individual SA linkage isomers. 25299151 6 67 theme reaction 1044:1051 arg1 monitoring 1053:1062 chromatography-selected reaction monitoring 1020:1062 a liquid chromatography-selected reaction monitoring (LC-SRM) approach that we demonstrate is capable of quantitating the individual SA linkage isomers 1011:1161 Here, we present a liquid chromatography-selected reaction monitoring (LC-SRM) approach that we demonstrate is capable of quantitating the individual SA linkage isomers. 25299151 7 68 dep Penta-HILIC 1324:1334 arg1 porous 1295:1300 porous 1295:1300 porous 1295:1300 The LC method is capable of separating sialylated N-glycan isomers differing in α2-3 and α2-6 linkages using a novel superficially porous particle (Fused-Core) Penta-HILIC (hydrophilic interaction liquid chromatography) column. 25299151 7 68 dep Penta-HILIC 1324:1334 arg1 chromatography 1368:1381 hydrophilic interaction liquid chromatography 1337:1381 hydrophilic interaction liquid chromatography 1337:1381 The LC method is capable of separating sialylated N-glycan isomers differing in α2-3 and α2-6 linkages using a novel superficially porous particle (Fused-Core) Penta-HILIC (hydrophilic interaction liquid chromatography) column. 25299151 5 69 theme SA 841:842 arg1 linkages 844:851 their SA linkages 835:851 their SA linkages 835:851 Consequently, quantitative methods to detect alterations in the ratios of glycans based on their SA linkages could serve as a diagnostic tool in oncology, yet traditional glycomic profiling cannot readily differentiate between these linkage isomers. 25299151 4 70 theme sialic 684:689 arg1 acid 691:694 α2-6 linked sialic acid 672:694 α2-6 linked sialic acid (SA) 672:699 For instance, previous studies have shown that the ratio of α2-3 to α2-6 linked sialic acid (SA) plays an important role in cancer biology. 25299151 4 70 theme sialic 684:689 arg1 SA 697:698 SA 697:698 SA 697:698 For instance, previous studies have shown that the ratio of α2-3 to α2-6 linked sialic acid (SA) plays an important role in cancer biology. 25299151 6 71 theme chromatography-selected 1020:1042 arg1 LC-SRM 1065:1070 LC-SRM 1065:1070 LC-SRM 1065:1070 Here, we present a liquid chromatography-selected reaction monitoring (LC-SRM) approach that we demonstrate is capable of quantitating the individual SA linkage isomers. 25299151 6 71 theme chromatography-selected 1020:1042 arg1 monitoring 1053:1062 chromatography-selected reaction monitoring 1020:1062 a liquid chromatography-selected reaction monitoring (LC-SRM) approach that we demonstrate is capable of quantitating the individual SA linkage isomers 1011:1161 Here, we present a liquid chromatography-selected reaction monitoring (LC-SRM) approach that we demonstrate is capable of quantitating the individual SA linkage isomers. 25299151 7 72 theme α2-6 1253:1256 arg1 linkages 1258:1265 α2-6 linkages 1253:1265 α2-6 linkages 1253:1265 The LC method is capable of separating sialylated N-glycan isomers differing in α2-3 and α2-6 linkages using a novel superficially porous particle (Fused-Core) Penta-HILIC (hydrophilic interaction liquid chromatography) column. 25299151 7 73 theme sialylated 1203:1212 arg1 isomers 1223:1229 sialylated N-glycan isomers 1203:1229 sialylated N-glycan isomers differing in α2-3 and α2-6 linkages using a novel superficially porous particle (Fused-Core) Penta-HILIC (hydrophilic interaction liquid chromatography) column 1203:1389 The LC method is capable of separating sialylated N-glycan isomers differing in α2-3 and α2-6 linkages using a novel superficially porous particle (Fused-Core) Penta-HILIC (hydrophilic interaction liquid chromatography) column. 25299151 9 74 theme chromatography-mass 1693:1711 arg1 LC-MS 1727:1731 LC-MS 1727:1731 LC-MS 1727:1731 With our approach, the relative quantitation of each SA linkage isomer is obtained from a straightforward liquid chromatography-mass spectrometry (LC-MS) experiment. 25299151 9 74 theme chromatography-mass 1693:1711 arg1 spectrometry 1713:1724 liquid chromatography-mass spectrometry 1686:1724 a straightforward liquid chromatography-mass spectrometry (LC-MS) experiment 1668:1743 With our approach, the relative quantitation of each SA linkage isomer is obtained from a straightforward liquid chromatography-mass spectrometry (LC-MS) experiment. 25299151 9 75 theme relative 1603:1610 arg1 quantitation 1612:1623 the relative quantitation 1599:1623 the relative quantitation of each SA linkage isomer 1599:1649 With our approach, the relative quantitation of each SA linkage isomer is obtained from a straightforward liquid chromatography-mass spectrometry (LC-MS) experiment. 25299151 5 76 theme glycans 818:824 arg1 ratios 808:813 the ratios 804:813 the ratios of glycans based on their SA linkages 804:851 Consequently, quantitative methods to detect alterations in the ratios of glycans based on their SA linkages could serve as a diagnostic tool in oncology, yet traditional glycomic profiling cannot readily differentiate between these linkage isomers. 25299151 6 77 theme liquid 1013:1018 arg1 approach 1073:1080 a liquid chromatography-selected reaction monitoring (LC-SRM) approach 1011:1080 a liquid chromatography-selected reaction monitoring (LC-SRM) approach that we demonstrate is capable of quantitating the individual SA linkage isomers 1011:1161 Here, we present a liquid chromatography-selected reaction monitoring (LC-SRM) approach that we demonstrate is capable of quantitating the individual SA linkage isomers. 26476268 0 0 theme Mecp2-mutant 83:94 arg1 models 103:108 Mecp2-mutant murine models 83:108 Mecp2-mutant murine models of Rett syndrome 83:125 Abnormal N-glycosylation pattern for brain nucleotide pyrophosphatase-5 (NPP-5) in Mecp2-mutant murine models of Rett syndrome. 26476268 0 1 from pattern 25:31 arg1 models 103:108 Mecp2-mutant murine models 83:108 Mecp2-mutant murine models of Rett syndrome 83:125 Abnormal N-glycosylation pattern for brain nucleotide pyrophosphatase-5 (NPP-5) in Mecp2-mutant murine models of Rett syndrome. 26476268 5 2 theme nucleotide 770:779 arg1 pyrophosphatase-5 781:797 the N-linked brain nucleotide pyrophosphatase-5 751:797 the N-linked brain nucleotide pyrophosphatase-5 751:797 Remarkable glycosylation pattern changes for a peculiar 50kDa protein, i.e., the N-linked brain nucleotide pyrophosphatase-5 were evidenced, with decreased N-glycosylation in the presymptomatic and symptomatic mutant mice. 26476268 6 3 theme selected 935:942 arg1 reactivation 956:967 selected brain Mecp2 reactivation 935:967 selected brain Mecp2 reactivation 935:967 Glycosylation changes were rescued by selected brain Mecp2 reactivation. 26476268 4 4 theme detection 510:518 arg1 strategies 520:529 Glycoprotein detection strategies 497:529 Glycoprotein detection strategies (i.e., lectin-blotting) 497:553 Glycoprotein detection strategies (i.e., lectin-blotting) were applied to identify target glycosylation changes in the whole brain of Mecp2 mutant murine models of the disease. 26476268 4 5 dep lectin-blotting 538:552 arg1 i.e. 532:535 i.e. 532:535 i.e. 532:535 Glycoprotein detection strategies (i.e., lectin-blotting) were applied to identify target glycosylation changes in the whole brain of Mecp2 mutant murine models of the disease. 26476268 4 6 theme glycosylation 587:599 arg1 changes 601:607 target glycosylation changes 580:607 target glycosylation changes in the whole brain of Mecp2 mutant murine models of the disease 580:671 Glycoprotein detection strategies (i.e., lectin-blotting) were applied to identify target glycosylation changes in the whole brain of Mecp2 mutant murine models of the disease. 26476268 6 7 theme brain 944:948 arg1 reactivation 956:967 selected brain Mecp2 reactivation 935:967 selected brain Mecp2 reactivation 935:967 Glycosylation changes were rescued by selected brain Mecp2 reactivation. 26476268 7 8 theme causal 1008:1013 arg1 link 1015:1018 a causal link 1006:1018 a causal link between the amount of Mecp2 and the N-glycosylation of NPP-5 1006:1079 Our findings indicate that there is a causal link between the amount of Mecp2 and the N-glycosylation of NPP-5. 26476268 4 9 theme disease 665:671 arg1 models 651:656 Mecp2 mutant murine models 631:656 Mecp2 mutant murine models of the disease 631:671 Glycoprotein detection strategies (i.e., lectin-blotting) were applied to identify target glycosylation changes in the whole brain of Mecp2 mutant murine models of the disease. 26476268 0 10 theme murine 96:101 arg1 models 103:108 Mecp2-mutant murine models 83:108 Mecp2-mutant murine models of Rett syndrome 83:125 Abnormal N-glycosylation pattern for brain nucleotide pyrophosphatase-5 (NPP-5) in Mecp2-mutant murine models of Rett syndrome. 26476268 5 11 theme peculiar 721:728 arg1 protein 736:742 a peculiar 50kDa protein 719:742 a peculiar 50kDa protein 719:742 Remarkable glycosylation pattern changes for a peculiar 50kDa protein, i.e., the N-linked brain nucleotide pyrophosphatase-5 were evidenced, with decreased N-glycosylation in the presymptomatic and symptomatic mutant mice. 26476268 5 12 theme Remarkable 674:683 arg1 changes 707:713 Remarkable glycosylation pattern changes 674:713 Remarkable glycosylation pattern changes for a peculiar 50kDa protein, i.e., the N-linked brain nucleotide pyrophosphatase-5 674:797 Remarkable glycosylation pattern changes for a peculiar 50kDa protein, i.e., the N-linked brain nucleotide pyrophosphatase-5 were evidenced, with decreased N-glycosylation in the presymptomatic and symptomatic mutant mice. 26476268 2 13 theme loss-of-function 291:306 arg1 mutations 308:316 de novo loss-of-function mutations 283:316 de novo loss-of-function mutations in the methyl-CpG binding protein 2 (MECP2) gene 283:365 Rett syndrome is a devastating genetic brain disorder, mainly caused by de novo loss-of-function mutations in the methyl-CpG binding protein 2 (MECP2) gene. 26476268 7 14 gly N-glycosylation 1056:1070 arg1 NPP-5 1075:1079 NPP-5 1075:1079 NPP-5 1075:1079 Our findings indicate that there is a causal link between the amount of Mecp2 and the N-glycosylation of NPP-5. 26476268 7 14 gly N-glycosylation 1056:1070 arg1 Mecp2 1042:1046 Mecp2 1042:1046 Mecp2 1042:1046 Our findings indicate that there is a causal link between the amount of Mecp2 and the N-glycosylation of NPP-5. 26476268 0 15 theme Rett 113:116 arg1 syndrome 118:125 Rett syndrome 113:125 Rett syndrome 113:125 Abnormal N-glycosylation pattern for brain nucleotide pyrophosphatase-5 (NPP-5) in Mecp2-mutant murine models of Rett syndrome. 26476268 5 16 theme decreased 820:828 arg1 N-glycosylation 830:844 decreased N-glycosylation 820:844 decreased N-glycosylation in the presymptomatic and symptomatic mutant mice 820:894 Remarkable glycosylation pattern changes for a peculiar 50kDa protein, i.e., the N-linked brain nucleotide pyrophosphatase-5 were evidenced, with decreased N-glycosylation in the presymptomatic and symptomatic mutant mice. 26476268 1 17 theme protein 174:180 arg1 abnormalities 196:208 protein glycosylation abnormalities 174:208 protein glycosylation abnormalities 174:208 Neurological disorders can be associated with protein glycosylation abnormalities. 26476268 4 18 theme Glycoprotein 497:508 arg1 strategies 520:529 Glycoprotein detection strategies 497:529 Glycoprotein detection strategies (i.e., lectin-blotting) 497:553 Glycoprotein detection strategies (i.e., lectin-blotting) were applied to identify target glycosylation changes in the whole brain of Mecp2 mutant murine models of the disease. 26476268 2 19 theme de 283:284 arg1 mutations 308:316 de novo loss-of-function mutations 283:316 de novo loss-of-function mutations in the methyl-CpG binding protein 2 (MECP2) gene 283:365 Rett syndrome is a devastating genetic brain disorder, mainly caused by de novo loss-of-function mutations in the methyl-CpG binding protein 2 (MECP2) gene. 26476268 1 20 theme glycosylation 182:194 arg1 abnormalities 196:208 protein glycosylation abnormalities 174:208 protein glycosylation abnormalities 174:208 Neurological disorders can be associated with protein glycosylation abnormalities. 26476268 0 21 theme N-glycosylation 9:23 arg1 pattern 25:31 Abnormal N-glycosylation pattern 0:31 Abnormal N-glycosylation pattern for brain nucleotide pyrophosphatase-5 (NPP-5) in Mecp2-mutant murine models of Rett syndrome. 0:126 Abnormal N-glycosylation pattern for brain nucleotide pyrophosphatase-5 (NPP-5) in Mecp2-mutant murine models of Rett syndrome. 26476268 5 22 from N-glycosylation 830:844 arg1 mice 891:894 the presymptomatic and symptomatic mutant mice 849:894 the presymptomatic and symptomatic mutant mice 849:894 Remarkable glycosylation pattern changes for a peculiar 50kDa protein, i.e., the N-linked brain nucleotide pyrophosphatase-5 were evidenced, with decreased N-glycosylation in the presymptomatic and symptomatic mutant mice. 26476268 2 23 theme binding 336:342 arg1 protein 344:350 the methyl-CpG binding protein 2 321:352 the methyl-CpG binding protein 2 (MECP2) gene 321:365 Rett syndrome is a devastating genetic brain disorder, mainly caused by de novo loss-of-function mutations in the methyl-CpG binding protein 2 (MECP2) gene. 26476268 2 23 theme binding 336:342 arg1 MECP2 355:359 MECP2 355:359 MECP2 355:359 Rett syndrome is a devastating genetic brain disorder, mainly caused by de novo loss-of-function mutations in the methyl-CpG binding protein 2 (MECP2) gene. 26476268 0 24 theme Abnormal 0:7 arg1 pattern 25:31 Abnormal N-glycosylation pattern 0:31 Abnormal N-glycosylation pattern for brain nucleotide pyrophosphatase-5 (NPP-5) in Mecp2-mutant murine models of Rett syndrome. 0:126 Abnormal N-glycosylation pattern for brain nucleotide pyrophosphatase-5 (NPP-5) in Mecp2-mutant murine models of Rett syndrome. 26476268 2 25 theme methyl-CpG 325:334 arg1 protein 344:350 the methyl-CpG binding protein 2 321:352 the methyl-CpG binding protein 2 (MECP2) gene 321:365 Rett syndrome is a devastating genetic brain disorder, mainly caused by de novo loss-of-function mutations in the methyl-CpG binding protein 2 (MECP2) gene. 26476268 2 25 theme methyl-CpG 325:334 arg1 MECP2 355:359 MECP2 355:359 MECP2 355:359 Rett syndrome is a devastating genetic brain disorder, mainly caused by de novo loss-of-function mutations in the methyl-CpG binding protein 2 (MECP2) gene. 26476268 3 26 theme redox 434:438 arg1 imbalance 440:448 a redox imbalance 432:448 a redox imbalance 432:448 Although its pathogenesis appears to be closely associated with a redox imbalance, no information on glycosylation is available. 26476268 5 27 link N-linked 755:762 arg1 pyrophosphatase-5 781:797 the N-linked brain nucleotide pyrophosphatase-5 751:797 the N-linked brain nucleotide pyrophosphatase-5 751:797 Remarkable glycosylation pattern changes for a peculiar 50kDa protein, i.e., the N-linked brain nucleotide pyrophosphatase-5 were evidenced, with decreased N-glycosylation in the presymptomatic and symptomatic mutant mice. 26476268 4 28 theme murine 644:649 arg1 models 651:656 Mecp2 mutant murine models 631:656 Mecp2 mutant murine models of the disease 631:671 Glycoprotein detection strategies (i.e., lectin-blotting) were applied to identify target glycosylation changes in the whole brain of Mecp2 mutant murine models of the disease. 26476268 4 29 theme target 580:585 arg1 changes 601:607 target glycosylation changes 580:607 target glycosylation changes in the whole brain of Mecp2 mutant murine models of the disease 580:671 Glycoprotein detection strategies (i.e., lectin-blotting) were applied to identify target glycosylation changes in the whole brain of Mecp2 mutant murine models of the disease. 26476268 0 30 theme syndrome 118:125 arg1 models 103:108 Mecp2-mutant murine models 83:108 Mecp2-mutant murine models of Rett syndrome 83:125 Abnormal N-glycosylation pattern for brain nucleotide pyrophosphatase-5 (NPP-5) in Mecp2-mutant murine models of Rett syndrome. 26476268 4 31 theme mutant 637:642 arg1 models 651:656 Mecp2 mutant murine models 631:656 Mecp2 mutant murine models of the disease 631:671 Glycoprotein detection strategies (i.e., lectin-blotting) were applied to identify target glycosylation changes in the whole brain of Mecp2 mutant murine models of the disease. 26476268 0 32 theme nucleotide 43:52 arg1 NPP-5 73:77 NPP-5 73:77 NPP-5 73:77 Abnormal N-glycosylation pattern for brain nucleotide pyrophosphatase-5 (NPP-5) in Mecp2-mutant murine models of Rett syndrome. 26476268 0 32 theme nucleotide 43:52 arg1 pyrophosphatase-5 54:70 brain nucleotide pyrophosphatase-5 37:70 brain nucleotide pyrophosphatase-5 (NPP-5) 37:78 Abnormal N-glycosylation pattern for brain nucleotide pyrophosphatase-5 (NPP-5) in Mecp2-mutant murine models of Rett syndrome. 26476268 5 33 dep pyrophosphatase-5 781:797 arg1 i.e. 745:748 i.e. 745:748 i.e. 745:748 Remarkable glycosylation pattern changes for a peculiar 50kDa protein, i.e., the N-linked brain nucleotide pyrophosphatase-5 were evidenced, with decreased N-glycosylation in the presymptomatic and symptomatic mutant mice. 26476268 5 34 theme 50kDa 730:734 arg1 protein 736:742 a peculiar 50kDa protein 719:742 a peculiar 50kDa protein 719:742 Remarkable glycosylation pattern changes for a peculiar 50kDa protein, i.e., the N-linked brain nucleotide pyrophosphatase-5 were evidenced, with decreased N-glycosylation in the presymptomatic and symptomatic mutant mice. 26476268 6 35 theme Glycosylation 897:909 arg1 changes 911:917 Glycosylation changes 897:917 Glycosylation changes 897:917 Glycosylation changes were rescued by selected brain Mecp2 reactivation. 26476268 5 36 gly N-glycosylation 830:844 arg1 mice 891:894 the presymptomatic and symptomatic mutant mice 849:894 the presymptomatic and symptomatic mutant mice 849:894 Remarkable glycosylation pattern changes for a peculiar 50kDa protein, i.e., the N-linked brain nucleotide pyrophosphatase-5 were evidenced, with decreased N-glycosylation in the presymptomatic and symptomatic mutant mice. 26476268 5 37 theme symptomatic 872:882 arg1 mice 891:894 the presymptomatic and symptomatic mutant mice 849:894 the presymptomatic and symptomatic mutant mice 849:894 Remarkable glycosylation pattern changes for a peculiar 50kDa protein, i.e., the N-linked brain nucleotide pyrophosphatase-5 were evidenced, with decreased N-glycosylation in the presymptomatic and symptomatic mutant mice. 26476268 0 38 theme brain 37:41 arg1 NPP-5 73:77 NPP-5 73:77 NPP-5 73:77 Abnormal N-glycosylation pattern for brain nucleotide pyrophosphatase-5 (NPP-5) in Mecp2-mutant murine models of Rett syndrome. 26476268 0 38 theme brain 37:41 arg1 pyrophosphatase-5 54:70 brain nucleotide pyrophosphatase-5 37:70 brain nucleotide pyrophosphatase-5 (NPP-5) 37:78 Abnormal N-glycosylation pattern for brain nucleotide pyrophosphatase-5 (NPP-5) in Mecp2-mutant murine models of Rett syndrome. 26476268 2 39 theme brain 250:254 arg1 syndrome 216:223 Rett syndrome 211:223 Rett syndrome 211:223 Rett syndrome is a devastating genetic brain disorder, mainly caused by de novo loss-of-function mutations in the methyl-CpG binding protein 2 (MECP2) gene. 26476268 2 39 theme brain 250:254 arg1 disorder 256:263 a devastating genetic brain disorder 228:263 a devastating genetic brain disorder 228:263 Rett syndrome is a devastating genetic brain disorder, mainly caused by de novo loss-of-function mutations in the methyl-CpG binding protein 2 (MECP2) gene. 26476268 5 40 theme mutant 884:889 arg1 mice 891:894 the presymptomatic and symptomatic mutant mice 849:894 the presymptomatic and symptomatic mutant mice 849:894 Remarkable glycosylation pattern changes for a peculiar 50kDa protein, i.e., the N-linked brain nucleotide pyrophosphatase-5 were evidenced, with decreased N-glycosylation in the presymptomatic and symptomatic mutant mice. 26476268 4 41 theme models 651:656 arg1 brain 622:626 the whole brain 612:626 the whole brain of Mecp2 mutant murine models of the disease 612:671 Glycoprotein detection strategies (i.e., lectin-blotting) were applied to identify target glycosylation changes in the whole brain of Mecp2 mutant murine models of the disease. 26476268 5 42 theme glycosylation 685:697 arg1 changes 707:713 Remarkable glycosylation pattern changes 674:713 Remarkable glycosylation pattern changes for a peculiar 50kDa protein, i.e., the N-linked brain nucleotide pyrophosphatase-5 674:797 Remarkable glycosylation pattern changes for a peculiar 50kDa protein, i.e., the N-linked brain nucleotide pyrophosphatase-5 were evidenced, with decreased N-glycosylation in the presymptomatic and symptomatic mutant mice. 26476268 2 43 theme genetic 242:248 arg1 syndrome 216:223 Rett syndrome 211:223 Rett syndrome 211:223 Rett syndrome is a devastating genetic brain disorder, mainly caused by de novo loss-of-function mutations in the methyl-CpG binding protein 2 (MECP2) gene. 26476268 2 43 theme genetic 242:248 arg1 disorder 256:263 a devastating genetic brain disorder 228:263 a devastating genetic brain disorder 228:263 Rett syndrome is a devastating genetic brain disorder, mainly caused by de novo loss-of-function mutations in the methyl-CpG binding protein 2 (MECP2) gene. 26476268 3 44 from information 454:464 arg1 glycosylation 469:481 glycosylation 469:481 glycosylation 469:481 Although its pathogenesis appears to be closely associated with a redox imbalance, no information on glycosylation is available. 26476268 5 45 theme pattern 699:705 arg1 changes 707:713 Remarkable glycosylation pattern changes 674:713 Remarkable glycosylation pattern changes for a peculiar 50kDa protein, i.e., the N-linked brain nucleotide pyrophosphatase-5 674:797 Remarkable glycosylation pattern changes for a peculiar 50kDa protein, i.e., the N-linked brain nucleotide pyrophosphatase-5 were evidenced, with decreased N-glycosylation in the presymptomatic and symptomatic mutant mice. 26476268 6 46 theme Mecp2 950:954 arg1 reactivation 956:967 selected brain Mecp2 reactivation 935:967 selected brain Mecp2 reactivation 935:967 Glycosylation changes were rescued by selected brain Mecp2 reactivation. 26476268 2 47 theme devastating 230:240 arg1 syndrome 216:223 Rett syndrome 211:223 Rett syndrome 211:223 Rett syndrome is a devastating genetic brain disorder, mainly caused by de novo loss-of-function mutations in the methyl-CpG binding protein 2 (MECP2) gene. 26476268 2 47 theme devastating 230:240 arg1 disorder 256:263 a devastating genetic brain disorder 228:263 a devastating genetic brain disorder 228:263 Rett syndrome is a devastating genetic brain disorder, mainly caused by de novo loss-of-function mutations in the methyl-CpG binding protein 2 (MECP2) gene. 26476268 7 48 theme Mecp2 1042:1046 arg1 NPP-5 1075:1079 NPP-5 1075:1079 NPP-5 1075:1079 Our findings indicate that there is a causal link between the amount of Mecp2 and the N-glycosylation of NPP-5. 26476268 7 48 theme Mecp2 1042:1046 arg1 Mecp2 1042:1046 Mecp2 1042:1046 Mecp2 1042:1046 Our findings indicate that there is a causal link between the amount of Mecp2 and the N-glycosylation of NPP-5. 26476268 7 48 theme Mecp2 1042:1046 arg1 N-glycosylation 1056:1070 the N-glycosylation 1052:1070 the N-glycosylation of NPP-5 1052:1079 Our findings indicate that there is a causal link between the amount of Mecp2 and the N-glycosylation of NPP-5. 26476268 7 48 theme Mecp2 1042:1046 arg1 amount 1032:1037 the amount 1028:1037 the amount of Mecp2 1028:1046 Our findings indicate that there is a causal link between the amount of Mecp2 and the N-glycosylation of NPP-5. 26476268 1 49 theme Neurological 128:139 arg1 disorders 141:149 Neurological disorders 128:149 Neurological disorders 128:149 Neurological disorders can be associated with protein glycosylation abnormalities. 26476268 4 50 from changes 601:607 arg1 brain 622:626 the whole brain 612:626 the whole brain of Mecp2 mutant murine models of the disease 612:671 Glycoprotein detection strategies (i.e., lectin-blotting) were applied to identify target glycosylation changes in the whole brain of Mecp2 mutant murine models of the disease. 26476268 2 51 theme protein 344:350 arg1 gene 362:365 the methyl-CpG binding protein 2 (MECP2) gene 321:365 the methyl-CpG binding protein 2 (MECP2) gene 321:365 Rett syndrome is a devastating genetic brain disorder, mainly caused by de novo loss-of-function mutations in the methyl-CpG binding protein 2 (MECP2) gene. 26476268 2 52 from mutations 308:316 arg1 gene 362:365 the methyl-CpG binding protein 2 (MECP2) gene 321:365 the methyl-CpG binding protein 2 (MECP2) gene 321:365 Rett syndrome is a devastating genetic brain disorder, mainly caused by de novo loss-of-function mutations in the methyl-CpG binding protein 2 (MECP2) gene. 26476268 4 53 theme whole 616:620 arg1 brain 622:626 the whole brain 612:626 the whole brain of Mecp2 mutant murine models of the disease 612:671 Glycoprotein detection strategies (i.e., lectin-blotting) were applied to identify target glycosylation changes in the whole brain of Mecp2 mutant murine models of the disease. 26476268 5 54 theme N-linked 755:762 arg1 pyrophosphatase-5 781:797 the N-linked brain nucleotide pyrophosphatase-5 751:797 the N-linked brain nucleotide pyrophosphatase-5 751:797 Remarkable glycosylation pattern changes for a peculiar 50kDa protein, i.e., the N-linked brain nucleotide pyrophosphatase-5 were evidenced, with decreased N-glycosylation in the presymptomatic and symptomatic mutant mice. 26476268 2 55 theme Rett 211:214 arg1 syndrome 216:223 Rett syndrome 211:223 Rett syndrome 211:223 Rett syndrome is a devastating genetic brain disorder, mainly caused by de novo loss-of-function mutations in the methyl-CpG binding protein 2 (MECP2) gene. 26476268 2 55 theme Rett 211:214 arg1 disorder 256:263 a devastating genetic brain disorder 228:263 a devastating genetic brain disorder 228:263 Rett syndrome is a devastating genetic brain disorder, mainly caused by de novo loss-of-function mutations in the methyl-CpG binding protein 2 (MECP2) gene. 26476268 7 56 theme NPP-5 1075:1079 arg1 NPP-5 1075:1079 NPP-5 1075:1079 NPP-5 1075:1079 Our findings indicate that there is a causal link between the amount of Mecp2 and the N-glycosylation of NPP-5. 26476268 7 56 theme NPP-5 1075:1079 arg1 Mecp2 1042:1046 Mecp2 1042:1046 Mecp2 1042:1046 Our findings indicate that there is a causal link between the amount of Mecp2 and the N-glycosylation of NPP-5. 26476268 7 56 theme NPP-5 1075:1079 arg1 N-glycosylation 1056:1070 the N-glycosylation 1052:1070 the N-glycosylation of NPP-5 1052:1079 Our findings indicate that there is a causal link between the amount of Mecp2 and the N-glycosylation of NPP-5. 26476268 7 56 theme NPP-5 1075:1079 arg1 amount 1032:1037 the amount 1028:1037 the amount of Mecp2 1028:1046 Our findings indicate that there is a causal link between the amount of Mecp2 and the N-glycosylation of NPP-5. 26476268 5 57 theme presymptomatic 853:866 arg1 mice 891:894 the presymptomatic and symptomatic mutant mice 849:894 the presymptomatic and symptomatic mutant mice 849:894 Remarkable glycosylation pattern changes for a peculiar 50kDa protein, i.e., the N-linked brain nucleotide pyrophosphatase-5 were evidenced, with decreased N-glycosylation in the presymptomatic and symptomatic mutant mice. 26476268 4 58 theme Mecp2 631:635 arg1 models 651:656 Mecp2 mutant murine models 631:656 Mecp2 mutant murine models of the disease 631:671 Glycoprotein detection strategies (i.e., lectin-blotting) were applied to identify target glycosylation changes in the whole brain of Mecp2 mutant murine models of the disease. 26476268 5 59 theme brain 764:768 arg1 pyrophosphatase-5 781:797 the N-linked brain nucleotide pyrophosphatase-5 751:797 the N-linked brain nucleotide pyrophosphatase-5 751:797 Remarkable glycosylation pattern changes for a peculiar 50kDa protein, i.e., the N-linked brain nucleotide pyrophosphatase-5 were evidenced, with decreased N-glycosylation in the presymptomatic and symptomatic mutant mice. 26476268 2 60 dep de 283:284 arg1 novo 286:289 novo 286:289 novo 286:289 Rett syndrome is a devastating genetic brain disorder, mainly caused by de novo loss-of-function mutations in the methyl-CpG binding protein 2 (MECP2) gene. 25857669 8 0 theme matrix 1271:1276 arg1 generation 1278:1287 monosaccharide substitution matrix generation 1243:1287 monosaccharide substitution matrix generation 1243:1287 GS-align is also applied to template-based glycan structure prediction and monosaccharide substitution matrix generation to illustrate its utility. 25857669 5 1 theme iterative 733:741 arg1 search 758:763 iterative maximum clique search 733:763 iterative maximum clique search 733:763 GS-align generates possible alignments between two glycan structures through iterative maximum clique search and fragment superposition. 25857669 4 2 theme structure 608:616 arg1 alignment 618:626 glycan structure alignment 601:626 glycan structure alignment 601:626 RESULTS A novel method, GS-align, is developed for glycan structure alignment and similarity measurement. 25857669 8 3 theme substitution 1258:1269 arg1 generation 1278:1287 monosaccharide substitution matrix generation 1243:1287 monosaccharide substitution matrix generation 1243:1287 GS-align is also applied to template-based glycan structure prediction and monosaccharide substitution matrix generation to illustrate its utility. 25857669 5 4 theme glycan 707:712 arg1 structures 714:723 two glycan structures 703:723 two glycan structures 703:723 GS-align generates possible alignments between two glycan structures through iterative maximum clique search and fragment superposition. 25857669 7 5 theme Data 951:954 arg1 PDB 962:964 PDB 962:964 PDB 962:964 Benchmark tests against the Protein Data Bank (PDB) N-linked glycan library and PDB homologous/non-homologous N-glycoprotein sets indicate that GS-align is a robust computational tool to align glycan structures and quantify their structural similarity. 25857669 7 5 theme Data 951:954 arg1 Bank 956:959 the Protein Data Bank 939:959 the Protein Data Bank (PDB) N-linked glycan library 939:989 Benchmark tests against the Protein Data Bank (PDB) N-linked glycan library and PDB homologous/non-homologous N-glycoprotein sets indicate that GS-align is a robust computational tool to align glycan structures and quantify their structural similarity. 25857669 4 6 theme glycan 601:606 arg1 alignment 618:626 glycan structure alignment 601:626 glycan structure alignment 601:626 RESULTS A novel method, GS-align, is developed for glycan structure alignment and similarity measurement. 25857669 7 7 theme N-glycoprotein 1025:1038 arg1 sets 1040:1043 PDB homologous/non-homologous N-glycoprotein sets 995:1043 PDB homologous/non-homologous N-glycoprotein sets 995:1043 Benchmark tests against the Protein Data Bank (PDB) N-linked glycan library and PDB homologous/non-homologous N-glycoprotein sets indicate that GS-align is a robust computational tool to align glycan structures and quantify their structural similarity. 25857669 7 8 theme Bank 956:959 arg1 library 983:989 the Protein Data Bank (PDB) N-linked glycan library 939:989 the Protein Data Bank (PDB) N-linked glycan library 939:989 Benchmark tests against the Protein Data Bank (PDB) N-linked glycan library and PDB homologous/non-homologous N-glycoprotein sets indicate that GS-align is a robust computational tool to align glycan structures and quantify their structural similarity. 25857669 8 9 theme glycan 1211:1216 arg1 prediction 1228:1237 template-based glycan structure prediction 1196:1237 template-based glycan structure prediction 1196:1237 GS-align is also applied to template-based glycan structure prediction and monosaccharide substitution matrix generation to illustrate its utility. 25857669 1 10 theme MOTIVATION 68:77 arg1 Glycans 79:85 MOTIVATION Glycans 68:85 MOTIVATION Glycans 68:85 MOTIVATION Glycans play critical roles in many biological processes, and their structural diversity is key for specific protein-glycan recognition. 25857669 3 11 theme protein 382:388 arg1 structure 390:398 protein structure 382:398 protein structure 382:398 However, most computational tools are designed for protein structure, and despite their importance, there is no currently available tool for comparing glycan structures in a sequence order- and size-independent manner. 25857669 9 12 dep //www.glycanstructure.org/gsalign 1353:1385 arg1 AVAILABILITY 1316:1327 AVAILABILITY 1316:1327 AVAILABILITY 1316:1327 AVAILABILITY AND IMPLEMENTATION http://www.glycanstructure.org/gsalign. 25857669 9 12 dep //www.glycanstructure.org/gsalign 1353:1385 arg1 IMPLEMENTATION 1333:1346 IMPLEMENTATION 1333:1346 IMPLEMENTATION 1333:1346 AVAILABILITY AND IMPLEMENTATION http://www.glycanstructure.org/gsalign. 25857669 2 13 theme biological 305:314 arg1 relationships 316:328 their biological relationships 299:328 their biological relationships 299:328 Comparative structural studies of biological molecules provide useful insight into their biological relationships. 25857669 1 14 theme specific 179:186 arg1 recognition 203:213 specific protein-glycan recognition 179:213 specific protein-glycan recognition 179:213 MOTIVATION Glycans play critical roles in many biological processes, and their structural diversity is key for specific protein-glycan recognition. 25857669 5 15 theme possible 675:682 arg1 alignments 684:693 possible alignments 675:693 possible alignments between two glycan structures 675:723 GS-align generates possible alignments between two glycan structures through iterative maximum clique search and fragment superposition. 25857669 7 16 theme homologous/non-homologous 999:1023 arg1 sets 1040:1043 PDB homologous/non-homologous N-glycoprotein sets 995:1043 PDB homologous/non-homologous N-glycoprotein sets 995:1043 Benchmark tests against the Protein Data Bank (PDB) N-linked glycan library and PDB homologous/non-homologous N-glycoprotein sets indicate that GS-align is a robust computational tool to align glycan structures and quantify their structural similarity. 25857669 10 17 theme @ 1402:1402 arg1 INFORMATION 1424:1434 CONTACT wonpil@ku.edu SUPPLEMENTARY INFORMATION 1388:1434 CONTACT wonpil@ku.edu SUPPLEMENTARY INFORMATION Supplementary data 1388:1453 CONTACT wonpil@ku.edu SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online. 25857669 6 18 theme similarity 860:869 arg1 GS-score 878:885 GS-score 878:885 GS-score 878:885 The optimal alignment is then determined by the maximum structural similarity score, GS-score, which is size-independent. 25857669 6 18 theme similarity 860:869 arg1 score 871:875 the maximum structural similarity score 837:875 the maximum structural similarity score 837:875 The optimal alignment is then determined by the maximum structural similarity score, GS-score, which is size-independent. 25857669 6 18 theme similarity 860:869 arg1 size-independent 897:912 size-independent 897:912 size-independent 897:912 The optimal alignment is then determined by the maximum structural similarity score, GS-score, which is size-independent. 25857669 1 19 theme critical 92:99 arg1 roles 101:105 critical roles 92:105 critical roles 92:105 MOTIVATION Glycans play critical roles in many biological processes, and their structural diversity is key for specific protein-glycan recognition. 25857669 5 20 theme maximum 743:749 arg1 search 758:763 iterative maximum clique search 733:763 iterative maximum clique search 733:763 GS-align generates possible alignments between two glycan structures through iterative maximum clique search and fragment superposition. 25857669 3 21 theme available 453:461 arg1 tool 463:466 no currently available tool 440:466 no currently available tool for comparing glycan structures in a sequence order- and size-independent manner 440:547 However, most computational tools are designed for protein structure, and despite their importance, there is no currently available tool for comparing glycan structures in a sequence order- and size-independent manner. 25857669 8 22 theme template-based 1196:1209 arg1 prediction 1228:1237 template-based glycan structure prediction 1196:1237 template-based glycan structure prediction 1196:1237 GS-align is also applied to template-based glycan structure prediction and monosaccharide substitution matrix generation to illustrate its utility. 25857669 6 23 theme structural 849:858 arg1 GS-score 878:885 GS-score 878:885 GS-score 878:885 The optimal alignment is then determined by the maximum structural similarity score, GS-score, which is size-independent. 25857669 6 23 theme structural 849:858 arg1 score 871:875 the maximum structural similarity score 837:875 the maximum structural similarity score 837:875 The optimal alignment is then determined by the maximum structural similarity score, GS-score, which is size-independent. 25857669 6 23 theme structural 849:858 arg1 size-independent 897:912 size-independent 897:912 size-independent 897:912 The optimal alignment is then determined by the maximum structural similarity score, GS-score, which is size-independent. 25857669 1 24 theme protein-glycan 188:201 arg1 recognition 203:213 specific protein-glycan recognition 179:213 specific protein-glycan recognition 179:213 MOTIVATION Glycans play critical roles in many biological processes, and their structural diversity is key for specific protein-glycan recognition. 25857669 0 25 theme structure 20:28 arg1 alignment 30:38 glycan structure alignment 13:38 glycan structure alignment 13:38 GS-align for glycan structure alignment and similarity measurement. 25857669 6 26 theme maximum 841:847 arg1 GS-score 878:885 GS-score 878:885 GS-score 878:885 The optimal alignment is then determined by the maximum structural similarity score, GS-score, which is size-independent. 25857669 6 26 theme maximum 841:847 arg1 score 871:875 the maximum structural similarity score 837:875 the maximum structural similarity score 837:875 The optimal alignment is then determined by the maximum structural similarity score, GS-score, which is size-independent. 25857669 6 26 theme maximum 841:847 arg1 size-independent 897:912 size-independent 897:912 size-independent 897:912 The optimal alignment is then determined by the maximum structural similarity score, GS-score, which is size-independent. 25857669 7 27 theme Benchmark 915:923 arg1 tests 925:929 Benchmark tests 915:929 Benchmark tests against the Protein Data Bank (PDB) N-linked glycan library 915:989 Benchmark tests against the Protein Data Bank (PDB) N-linked glycan library and PDB homologous/non-homologous N-glycoprotein sets indicate that GS-align is a robust computational tool to align glycan structures and quantify their structural similarity. 25857669 0 28 theme glycan 13:18 arg1 alignment 30:38 glycan structure alignment 13:38 glycan structure alignment 13:38 GS-align for glycan structure alignment and similarity measurement. 25857669 5 29 theme fragment 769:776 arg1 superposition 778:790 fragment superposition 769:790 fragment superposition 769:790 GS-align generates possible alignments between two glycan structures through iterative maximum clique search and fragment superposition. 25857669 1 30 theme many 110:113 arg1 processes 126:134 many biological processes 110:134 many biological processes 110:134 MOTIVATION Glycans play critical roles in many biological processes, and their structural diversity is key for specific protein-glycan recognition. 25857669 7 31 theme Protein 943:949 arg1 PDB 962:964 PDB 962:964 PDB 962:964 Benchmark tests against the Protein Data Bank (PDB) N-linked glycan library and PDB homologous/non-homologous N-glycoprotein sets indicate that GS-align is a robust computational tool to align glycan structures and quantify their structural similarity. 25857669 7 31 theme Protein 943:949 arg1 Bank 956:959 the Protein Data Bank 939:959 the Protein Data Bank (PDB) N-linked glycan library 939:989 Benchmark tests against the Protein Data Bank (PDB) N-linked glycan library and PDB homologous/non-homologous N-glycoprotein sets indicate that GS-align is a robust computational tool to align glycan structures and quantify their structural similarity. 25857669 7 32 theme structural 1145:1154 arg1 similarity 1156:1165 their structural similarity 1139:1165 their structural similarity 1139:1165 Benchmark tests against the Protein Data Bank (PDB) N-linked glycan library and PDB homologous/non-homologous N-glycoprotein sets indicate that GS-align is a robust computational tool to align glycan structures and quantify their structural similarity. 25857669 10 33 theme SUPPLEMENTARY 1410:1422 arg1 INFORMATION 1424:1434 CONTACT wonpil@ku.edu SUPPLEMENTARY INFORMATION 1388:1434 CONTACT wonpil@ku.edu SUPPLEMENTARY INFORMATION Supplementary data 1388:1453 CONTACT wonpil@ku.edu SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online. 25857669 2 34 theme molecules 261:269 arg1 studies 239:245 Comparative structural studies 216:245 Comparative structural studies of biological molecules 216:269 Comparative structural studies of biological molecules provide useful insight into their biological relationships. 25857669 10 35 theme Bioinformatics 1472:1485 arg1 online 1487:1492 Bioinformatics online 1472:1492 Bioinformatics online 1472:1492 CONTACT wonpil@ku.edu SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online. 25857669 3 36 theme glycan 482:487 arg1 structures 489:498 glycan structures 482:498 glycan structures 482:498 However, most computational tools are designed for protein structure, and despite their importance, there is no currently available tool for comparing glycan structures in a sequence order- and size-independent manner. 25857669 9 37 dep AVAILABILITY 1316:1327 arg1 http 1348:1351 http 1348:1351 http 1348:1351 AVAILABILITY AND IMPLEMENTATION http://www.glycanstructure.org/gsalign. 25857669 10 38 theme INFORMATION 1424:1434 arg1 data 1450:1453 CONTACT wonpil@ku.edu SUPPLEMENTARY INFORMATION Supplementary data 1388:1453 CONTACT wonpil@ku.edu SUPPLEMENTARY INFORMATION Supplementary data 1388:1453 CONTACT wonpil@ku.edu SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online. 25857669 2 39 theme biological 250:259 arg1 molecules 261:269 biological molecules 250:269 biological molecules 250:269 Comparative structural studies of biological molecules provide useful insight into their biological relationships. 25857669 4 40 theme novel 560:564 arg1 GS-align 574:581 GS-align 574:581 GS-align 574:581 RESULTS A novel method, GS-align, is developed for glycan structure alignment and similarity measurement. 25857669 4 40 theme novel 560:564 arg1 method 566:571 A novel method 558:571 A novel method 558:571 RESULTS A novel method, GS-align, is developed for glycan structure alignment and similarity measurement. 25857669 3 41 theme most 340:343 arg1 tools 359:363 most computational tools 340:363 most computational tools 340:363 However, most computational tools are designed for protein structure, and despite their importance, there is no currently available tool for comparing glycan structures in a sequence order- and size-independent manner. 25857669 7 42 theme glycan 1108:1113 arg1 structures 1115:1124 glycan structures 1108:1124 glycan structures 1108:1124 Benchmark tests against the Protein Data Bank (PDB) N-linked glycan library and PDB homologous/non-homologous N-glycoprotein sets indicate that GS-align is a robust computational tool to align glycan structures and quantify their structural similarity. 25857669 1 43 theme biological 115:124 arg1 processes 126:134 many biological processes 110:134 many biological processes 110:134 MOTIVATION Glycans play critical roles in many biological processes, and their structural diversity is key for specific protein-glycan recognition. 25857669 0 44 theme similarity 44:53 arg1 measurement 55:65 similarity measurement 44:65 similarity measurement 44:65 GS-align for glycan structure alignment and similarity measurement. 25857669 3 45 theme computational 345:357 arg1 tools 359:363 most computational tools 340:363 most computational tools 340:363 However, most computational tools are designed for protein structure, and despite their importance, there is no currently available tool for comparing glycan structures in a sequence order- and size-independent manner. 25857669 2 46 theme structural 228:237 arg1 studies 239:245 Comparative structural studies 216:245 Comparative structural studies of biological molecules 216:269 Comparative structural studies of biological molecules provide useful insight into their biological relationships. 25857669 7 47 link N-linked 967:974 arg1 library 983:989 the Protein Data Bank (PDB) N-linked glycan library 939:989 the Protein Data Bank (PDB) N-linked glycan library 939:989 Benchmark tests against the Protein Data Bank (PDB) N-linked glycan library and PDB homologous/non-homologous N-glycoprotein sets indicate that GS-align is a robust computational tool to align glycan structures and quantify their structural similarity. 25857669 3 48 theme size-independent 525:540 arg1 manner 542:547 a sequence order- and size-independent manner 503:547 a sequence order- and size-independent manner 503:547 However, most computational tools are designed for protein structure, and despite their importance, there is no currently available tool for comparing glycan structures in a sequence order- and size-independent manner. 25857669 7 49 theme glycan 976:981 arg1 library 983:989 the Protein Data Bank (PDB) N-linked glycan library 939:989 the Protein Data Bank (PDB) N-linked glycan library 939:989 Benchmark tests against the Protein Data Bank (PDB) N-linked glycan library and PDB homologous/non-homologous N-glycoprotein sets indicate that GS-align is a robust computational tool to align glycan structures and quantify their structural similarity. 25857669 7 50 theme PDB 995:997 arg1 sets 1040:1043 PDB homologous/non-homologous N-glycoprotein sets 995:1043 PDB homologous/non-homologous N-glycoprotein sets 995:1043 Benchmark tests against the Protein Data Bank (PDB) N-linked glycan library and PDB homologous/non-homologous N-glycoprotein sets indicate that GS-align is a robust computational tool to align glycan structures and quantify their structural similarity. 25857669 5 51 theme clique 751:756 arg1 search 758:763 iterative maximum clique search 733:763 iterative maximum clique search 733:763 GS-align generates possible alignments between two glycan structures through iterative maximum clique search and fragment superposition. 25857669 2 52 theme Comparative 216:226 arg1 studies 239:245 Comparative structural studies 216:245 Comparative structural studies of biological molecules 216:269 Comparative structural studies of biological molecules provide useful insight into their biological relationships. 25857669 10 53 from online 1487:1492 arg1 available 1459:1467 available 1459:1467 available 1459:1467 CONTACT wonpil@ku.edu SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online. 25857669 10 54 theme wonpil 1396:1401 arg1 INFORMATION 1424:1434 CONTACT wonpil@ku.edu SUPPLEMENTARY INFORMATION 1388:1434 CONTACT wonpil@ku.edu SUPPLEMENTARY INFORMATION Supplementary data 1388:1453 CONTACT wonpil@ku.edu SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online. 25857669 7 55 gly N-glycoprotein 1025:1038 arg1 N-glycoprotein 1025:1038 PDB homologous/non-homologous N-glycoprotein sets 995:1043 PDB homologous/non-homologous N-glycoprotein sets 995:1043 Benchmark tests against the Protein Data Bank (PDB) N-linked glycan library and PDB homologous/non-homologous N-glycoprotein sets indicate that GS-align is a robust computational tool to align glycan structures and quantify their structural similarity. 25857669 8 56 theme structure 1218:1226 arg1 prediction 1228:1237 template-based glycan structure prediction 1196:1237 template-based glycan structure prediction 1196:1237 GS-align is also applied to template-based glycan structure prediction and monosaccharide substitution matrix generation to illustrate its utility. 25857669 7 57 theme robust 1073:1078 arg1 tool 1094:1097 a robust computational tool 1071:1097 a robust computational tool to align glycan structures and quantify their structural similarity 1071:1165 Benchmark tests against the Protein Data Bank (PDB) N-linked glycan library and PDB homologous/non-homologous N-glycoprotein sets indicate that GS-align is a robust computational tool to align glycan structures and quantify their structural similarity. 25857669 7 57 theme robust 1073:1078 arg1 GS-align 1059:1066 GS-align 1059:1066 GS-align 1059:1066 Benchmark tests against the Protein Data Bank (PDB) N-linked glycan library and PDB homologous/non-homologous N-glycoprotein sets indicate that GS-align is a robust computational tool to align glycan structures and quantify their structural similarity. 25857669 3 58 theme order- 514:519 arg1 manner 542:547 a sequence order- and size-independent manner 503:547 a sequence order- and size-independent manner 503:547 However, most computational tools are designed for protein structure, and despite their importance, there is no currently available tool for comparing glycan structures in a sequence order- and size-independent manner. 25857669 10 59 theme CONTACT 1388:1394 arg1 INFORMATION 1424:1434 CONTACT wonpil@ku.edu SUPPLEMENTARY INFORMATION 1388:1434 CONTACT wonpil@ku.edu SUPPLEMENTARY INFORMATION Supplementary data 1388:1453 CONTACT wonpil@ku.edu SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online. 25857669 4 60 theme similarity 632:641 arg1 measurement 643:653 similarity measurement 632:653 similarity measurement 632:653 RESULTS A novel method, GS-align, is developed for glycan structure alignment and similarity measurement. 25857669 8 61 theme monosaccharide 1243:1256 arg1 generation 1278:1287 monosaccharide substitution matrix generation 1243:1287 monosaccharide substitution matrix generation 1243:1287 GS-align is also applied to template-based glycan structure prediction and monosaccharide substitution matrix generation to illustrate its utility. 25857669 10 62 theme ku.edu 1403:1408 arg1 INFORMATION 1424:1434 CONTACT wonpil@ku.edu SUPPLEMENTARY INFORMATION 1388:1434 CONTACT wonpil@ku.edu SUPPLEMENTARY INFORMATION Supplementary data 1388:1453 CONTACT wonpil@ku.edu SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online. 25857669 2 63 theme useful 279:284 arg1 insight 286:292 useful insight 279:292 useful insight into their biological relationships 279:328 Comparative structural studies of biological molecules provide useful insight into their biological relationships. 25857669 7 64 theme computational 1080:1092 arg1 tool 1094:1097 a robust computational tool 1071:1097 a robust computational tool to align glycan structures and quantify their structural similarity 1071:1165 Benchmark tests against the Protein Data Bank (PDB) N-linked glycan library and PDB homologous/non-homologous N-glycoprotein sets indicate that GS-align is a robust computational tool to align glycan structures and quantify their structural similarity. 25857669 7 64 theme computational 1080:1092 arg1 GS-align 1059:1066 GS-align 1059:1066 GS-align 1059:1066 Benchmark tests against the Protein Data Bank (PDB) N-linked glycan library and PDB homologous/non-homologous N-glycoprotein sets indicate that GS-align is a robust computational tool to align glycan structures and quantify their structural similarity. 25857669 7 65 theme N-linked 967:974 arg1 library 983:989 the Protein Data Bank (PDB) N-linked glycan library 939:989 the Protein Data Bank (PDB) N-linked glycan library 939:989 Benchmark tests against the Protein Data Bank (PDB) N-linked glycan library and PDB homologous/non-homologous N-glycoprotein sets indicate that GS-align is a robust computational tool to align glycan structures and quantify their structural similarity. 25857669 6 66 theme optimal 797:803 arg1 alignment 805:813 The optimal alignment 793:813 The optimal alignment 793:813 The optimal alignment is then determined by the maximum structural similarity score, GS-score, which is size-independent. 25857669 1 67 theme structural 147:156 arg1 diversity 158:166 their structural diversity 141:166 their structural diversity 141:166 MOTIVATION Glycans play critical roles in many biological processes, and their structural diversity is key for specific protein-glycan recognition. 25857669 10 68 theme Supplementary 1436:1448 arg1 data 1450:1453 CONTACT wonpil@ku.edu SUPPLEMENTARY INFORMATION Supplementary data 1388:1453 CONTACT wonpil@ku.edu SUPPLEMENTARY INFORMATION Supplementary data 1388:1453 CONTACT wonpil@ku.edu SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online. 25857669 4 69 dep RESULTS 550:556 arg1 developed 587:595 developed 587:595 is developed for glycan structure alignment and similarity measurement 584:653 RESULTS A novel method, GS-align, is developed for glycan structure alignment and similarity measurement. 25736888 4 0 theme C. canimorsus 834:846 arg1 strain 848:853 C. canimorsus strain 5 834:855 C. canimorsus strain 5 834:855 Accordingly, a genome analysis was conducted and revealed that C. canimorsus strain 5 lacks the GlmM and GlmU enzymes, which convert glucosamine into GlcNAc. 25736888 3 1 theme locus 486:490 arg1 PUL5 495:498 Polysaccharide utilization locus 5 (PUL5) and sialidase mutant bacteria 459:529 PUL5 495:498 Polysaccharide utilization locus 5 (PUL5) and sialidase mutant bacteria, unable to retrieve glycans from glycoproteins, grew less than wild-type bacteria and also appeared polymorphic unless GlcNAc was added, suggesting that C. canimorsus is unable to synthesize GlcNAc, an essential component of peptidoglycan. 25736888 9 2 theme glycan-rich 1593:1603 arg1 glycoproteins 1617:1629 the glycan-rich dog's mouth glycoproteins 1589:1629 the glycan-rich dog's mouth glycoproteins 1589:1629 Thus, C. canimorsus has adapted to build its peptidoglycan from the glycan-rich dog's mouth glycoproteins. 25736888 3 3 theme sialidase 505:513 arg1 bacteria 522:529 Polysaccharide utilization locus 5 (PUL5) and sialidase mutant bacteria 459:529 bacteria 522:529 Polysaccharide utilization locus 5 (PUL5) and sialidase mutant bacteria, unable to retrieve glycans from glycoproteins, grew less than wild-type bacteria and also appeared polymorphic unless GlcNAc was added, suggesting that C. canimorsus is unable to synthesize GlcNAc, an essential component of peptidoglycan. 25736888 16 4 theme C. canimorsus 2579:2591 arg1 adaptation 2565:2574 the complex adaptation 2553:2574 the complex adaptation of C. canimorsus to its ecological niche, the oral cavity of dogs 2553:2640 This study provides a molecular genetic demonstration for the complex adaptation of C. canimorsus to its ecological niche, the oral cavity of dogs. 25736888 15 5 theme glycan 2480:2485 arg1 chains 2487:2492 glycan chains 2480:2492 glycan chains 2480:2492 The Muc system is peculiar in the sense that the enzyme of the complex is a protease and not a glycosylhydrolase, as it cleaves peptide bonds in order to capture glycan chains. 25736888 1 6 theme blood 169:173 arg1 plates 180:185 blood agar plates 169:185 blood agar plates (coccoid and bacillary) 169:209 UNLABELLED Capnocytophaga canimorsus is known to form two kinds of cells on blood agar plates (coccoid and bacillary), evoking phase variation. 25736888 14 7 link N-linked 2175:2182 arg1 glycoproteins 2184:2196 salivary mucin and N-linked glycoproteins 2156:2196 glycoproteins 2184:2196 In its niche, the dog mouth, C. canimorsus retrieves GlcNAc by foraging glycans from salivary mucin and N-linked glycoproteins through two different apparatuses, Muc and Gpd, both of which are related to the Bacteroides starch utilization system. 25736888 5 8 theme GlmU 1015:1018 arg1 GlmU 1015:1018 GlmU 1015:1018 GlmU 1015:1018 Expression of the Escherichia coli GlmM together with the acetyltransferase domain of GlmU allowed PUL5 mutant bacteria to grow normally, indicating that C. canimorsus is a natural auxotroph that relies on GlcNAc harvested from the host N-glycoproteins for peptidoglycan synthesis. 25736888 5 8 theme GlmU 1015:1018 arg1 domain 1005:1010 the acetyltransferase domain 983:1010 the acetyltransferase domain of GlmU 983:1018 Expression of the Escherichia coli GlmM together with the acetyltransferase domain of GlmU allowed PUL5 mutant bacteria to grow normally, indicating that C. canimorsus is a natural auxotroph that relies on GlcNAc harvested from the host N-glycoproteins for peptidoglycan synthesis. 25736888 15 9 from sense 2352:2356 arg1 peculiar 2336:2343 peculiar 2336:2343 peculiar 2336:2343 The Muc system is peculiar in the sense that the enzyme of the complex is a protease and not a glycosylhydrolase, as it cleaves peptide bonds in order to capture glycan chains. 25736888 15 9 from sense 2352:2356 arg1 system 2326:2331 The Muc system 2318:2331 The Muc system 2318:2331 The Muc system is peculiar in the sense that the enzyme of the complex is a protease and not a glycosylhydrolase, as it cleaves peptide bonds in order to capture glycan chains. 25736888 6 10 theme PUL5 1308:1311 arg1 bacteria 1320:1327 PUL5 mutant bacteria 1308:1327 PUL5 mutant bacteria 1308:1327 Mucin, a heavily O-glycosylated protein abundant in saliva, also rescued growth and the shape of PUL5 mutant bacteria. 25736888 3 11 theme essential 733:741 arg1 GlcNAc 722:727 GlcNAc 722:727 GlcNAc 722:727 Polysaccharide utilization locus 5 (PUL5) and sialidase mutant bacteria, unable to retrieve glycans from glycoproteins, grew less than wild-type bacteria and also appeared polymorphic unless GlcNAc was added, suggesting that C. canimorsus is unable to synthesize GlcNAc, an essential component of peptidoglycan. 25736888 3 11 theme essential 733:741 arg1 component 743:751 an essential component 730:751 an essential component of peptidoglycan 730:768 Polysaccharide utilization locus 5 (PUL5) and sialidase mutant bacteria, unable to retrieve glycans from glycoproteins, grew less than wild-type bacteria and also appeared polymorphic unless GlcNAc was added, suggesting that C. canimorsus is unable to synthesize GlcNAc, an essential component of peptidoglycan. 25736888 13 12 theme key 2058:2060 arg1 enzymes 2062:2068 key enzymes 2058:2068 key enzymes 2058:2068 C. canimorsus cannot synthesize GlcNAc because of the lack of key enzymes. 25736888 14 13 gly glycoproteins 2184:2196 arg1 glycoproteins 2184:2196 salivary mucin and N-linked glycoproteins 2156:2196 glycoproteins 2184:2196 In its niche, the dog mouth, C. canimorsus retrieves GlcNAc by foraging glycans from salivary mucin and N-linked glycoproteins through two different apparatuses, Muc and Gpd, both of which are related to the Bacteroides starch utilization system. 25736888 7 14 theme mucin 1345:1349 arg1 Utilization 1330:1340 Utilization 1330:1340 Utilization of mucin 1330:1349 Utilization of mucin was found to depend on Muc, a Sus-like system encoded by PUL9. 25736888 13 15 theme C. canimorsus 1996:2008 arg1 cannot 2010:2015 C. canimorsus cannot 1996:2015 C. canimorsus cannot 1996:2015 C. canimorsus cannot synthesize GlcNAc because of the lack of key enzymes. 25736888 16 16 theme dogs 2637:2640 arg1 cavity 2627:2632 the oral cavity 2618:2632 the oral cavity of dogs 2618:2640 This study provides a molecular genetic demonstration for the complex adaptation of C. canimorsus to its ecological niche, the oral cavity of dogs. 25736888 16 16 theme dogs 2637:2640 arg1 niche 2611:2615 its ecological niche 2596:2615 its ecological niche 2596:2615 This study provides a molecular genetic demonstration for the complex adaptation of C. canimorsus to its ecological niche, the oral cavity of dogs. 25736888 5 17 theme PUL5 1028:1031 arg1 bacteria 1040:1047 PUL5 mutant bacteria 1028:1047 PUL5 mutant bacteria 1028:1047 Expression of the Escherichia coli GlmM together with the acetyltransferase domain of GlmU allowed PUL5 mutant bacteria to grow normally, indicating that C. canimorsus is a natural auxotroph that relies on GlcNAc harvested from the host N-glycoproteins for peptidoglycan synthesis. 25736888 10 18 theme dog 1717:1719 arg1 mouth 1721:1725 the dog mouth 1713:1725 the dog mouth 1713:1725 IMPORTANCE Capnocytophaga canimorsus is a bacterium that lives as a commensal in the dog mouth and causes severe infections in humans. 25736888 6 19 gly O-glycosylated 1228:1241 arg1 protein 1243:1249 a heavily O-glycosylated protein 1218:1249 a heavily O-glycosylated protein abundant in saliva 1218:1268 Mucin, a heavily O-glycosylated protein abundant in saliva, also rescued growth and the shape of PUL5 mutant bacteria. 25736888 6 19 gly O-glycosylated 1228:1241 arg1 Mucin 1211:1215 Mucin 1211:1215 Mucin 1211:1215 Mucin, a heavily O-glycosylated protein abundant in saliva, also rescued growth and the shape of PUL5 mutant bacteria. 25736888 8 20 theme known 1430:1434 arg1 systems 1448:1454 all known PUL-encoded systems 1426:1454 all known PUL-encoded systems 1426:1454 Contrary to all known PUL-encoded systems, Muc cleaves peptide bonds of mucin rather than glycosidic linkages. 25736888 13 21 theme enzymes 2062:2068 arg1 lack 2050:2053 the lack 2046:2053 the lack of key enzymes 2046:2068 C. canimorsus cannot synthesize GlcNAc because of the lack of key enzymes. 25736888 15 22 theme Muc 2322:2324 arg1 peculiar 2336:2343 peculiar 2336:2343 peculiar 2336:2343 The Muc system is peculiar in the sense that the enzyme of the complex is a protease and not a glycosylhydrolase, as it cleaves peptide bonds in order to capture glycan chains. 25736888 15 22 theme Muc 2322:2324 arg1 system 2326:2331 The Muc system 2318:2331 The Muc system 2318:2331 The Muc system is peculiar in the sense that the enzyme of the complex is a protease and not a glycosylhydrolase, as it cleaves peptide bonds in order to capture glycan chains. 25736888 2 23 theme layer 452:456 arg1 weakening 421:429 weakening 421:429 weakening of the peptidoglycan layer 421:456 When grown in coculture with animal cells these bacteria appeared only as bacilli, but in the presence of vancomycin they were round, indicating that coccoid shapes likely result from weakening of the peptidoglycan layer. 25736888 12 24 theme N-acetylglucosamine 1966:1984 arg1 shortage 1954:1961 a shortage 1952:1961 a shortage of N-acetylglucosamine (GlcNAc) 1952:1993 Here, we show that cell rounding likely results from weakening of the peptidoglycan layer due to a shortage of N-acetylglucosamine (GlcNAc). 25736888 14 25 theme different 2210:2218 arg1 Muc 2233:2235 Muc 2233:2235 Muc 2233:2235 In its niche, the dog mouth, C. canimorsus retrieves GlcNAc by foraging glycans from salivary mucin and N-linked glycoproteins through two different apparatuses, Muc and Gpd, both of which are related to the Bacteroides starch utilization system. 25736888 14 25 theme different 2210:2218 arg1 apparatuses 2220:2230 two different apparatuses 2206:2230 two different apparatuses 2206:2230 In its niche, the dog mouth, C. canimorsus retrieves GlcNAc by foraging glycans from salivary mucin and N-linked glycoproteins through two different apparatuses, Muc and Gpd, both of which are related to the Bacteroides starch utilization system. 25736888 14 25 theme different 2210:2218 arg1 Gpd 2241:2243 Gpd 2241:2243 Gpd 2241:2243 In its niche, the dog mouth, C. canimorsus retrieves GlcNAc by foraging glycans from salivary mucin and N-linked glycoproteins through two different apparatuses, Muc and Gpd, both of which are related to the Bacteroides starch utilization system. 25736888 0 26 theme dog 82:84 arg1 mouth 86:90 the dog mouth 78:90 the dog mouth 78:90 Glycan-foraging systems reveal the adaptation of Capnocytophaga canimorsus to the dog mouth. 25736888 5 27 theme natural 1102:1108 arg1 C. canimorsus 1083:1095 C. canimorsus 1083:1095 C. canimorsus 1083:1095 Expression of the Escherichia coli GlmM together with the acetyltransferase domain of GlmU allowed PUL5 mutant bacteria to grow normally, indicating that C. canimorsus is a natural auxotroph that relies on GlcNAc harvested from the host N-glycoproteins for peptidoglycan synthesis. 25736888 5 27 theme natural 1102:1108 arg1 auxotroph 1110:1118 a natural auxotroph 1100:1118 a natural auxotroph that relies on GlcNAc harvested from the host N-glycoproteins for peptidoglycan synthesis 1100:1208 Expression of the Escherichia coli GlmM together with the acetyltransferase domain of GlmU allowed PUL5 mutant bacteria to grow normally, indicating that C. canimorsus is a natural auxotroph that relies on GlcNAc harvested from the host N-glycoproteins for peptidoglycan synthesis. 25736888 1 28 theme cells 160:164 arg1 kinds 151:155 two kinds 147:155 two kinds of cells 147:164 UNLABELLED Capnocytophaga canimorsus is known to form two kinds of cells on blood agar plates (coccoid and bacillary), evoking phase variation. 25736888 8 29 theme peptide 1469:1475 arg1 bonds 1477:1481 peptide bonds 1469:1481 peptide bonds of mucin rather than glycosidic linkages 1469:1522 Contrary to all known PUL-encoded systems, Muc cleaves peptide bonds of mucin rather than glycosidic linkages. 25736888 14 30 theme N-linked 2175:2182 arg1 glycoproteins 2184:2196 salivary mucin and N-linked glycoproteins 2156:2196 glycoproteins 2184:2196 In its niche, the dog mouth, C. canimorsus retrieves GlcNAc by foraging glycans from salivary mucin and N-linked glycoproteins through two different apparatuses, Muc and Gpd, both of which are related to the Bacteroides starch utilization system. 25736888 6 31 theme bacteria 1320:1327 arg1 growth 1284:1289 growth 1284:1289 growth 1284:1289 Mucin, a heavily O-glycosylated protein abundant in saliva, also rescued growth and the shape of PUL5 mutant bacteria. 25736888 6 31 theme bacteria 1320:1327 arg1 shape 1299:1303 the shape 1295:1303 the shape 1295:1303 Mucin, a heavily O-glycosylated protein abundant in saliva, also rescued growth and the shape of PUL5 mutant bacteria. 25736888 15 32 theme complex 2381:2387 arg1 protease 2394:2401 a protease and not a glycosylhydrolase 2392:2429 protease 2394:2401 The Muc system is peculiar in the sense that the enzyme of the complex is a protease and not a glycosylhydrolase, as it cleaves peptide bonds in order to capture glycan chains. 25736888 15 32 theme complex 2381:2387 arg1 enzyme 2367:2372 the enzyme 2363:2372 the enzyme of the complex 2363:2387 The Muc system is peculiar in the sense that the enzyme of the complex is a protease and not a glycosylhydrolase, as it cleaves peptide bonds in order to capture glycan chains. 25736888 14 33 from mucin 2165:2169 arg1 glycans 2143:2149 glycans 2143:2149 glycans from salivary mucin and N-linked glycoproteins 2143:2196 In its niche, the dog mouth, C. canimorsus retrieves GlcNAc by foraging glycans from salivary mucin and N-linked glycoproteins through two different apparatuses, Muc and Gpd, both of which are related to the Bacteroides starch utilization system. 25736888 5 34 gly N-glycoproteins 1166:1180 arg1 N-glycoproteins 1166:1180 the host N-glycoproteins 1157:1180 the host N-glycoproteins for peptidoglycan synthesis 1157:1208 Expression of the Escherichia coli GlmM together with the acetyltransferase domain of GlmU allowed PUL5 mutant bacteria to grow normally, indicating that C. canimorsus is a natural auxotroph that relies on GlcNAc harvested from the host N-glycoproteins for peptidoglycan synthesis. 25736888 2 35 theme vancomycin 343:352 arg1 round 364:368 round 364:368 round 364:368 When grown in coculture with animal cells these bacteria appeared only as bacilli, but in the presence of vancomycin they were round, indicating that coccoid shapes likely result from weakening of the peptidoglycan layer. 25736888 0 36 theme Glycan-foraging 0:14 arg1 systems 16:22 Glycan-foraging systems 0:22 Glycan-foraging systems 0:22 Glycan-foraging systems reveal the adaptation of Capnocytophaga canimorsus to the dog mouth. 25736888 1 37 theme UNLABELLED 93:102 arg1 canimorsus 119:128 UNLABELLED Capnocytophaga canimorsus 93:128 UNLABELLED Capnocytophaga canimorsus 93:128 UNLABELLED Capnocytophaga canimorsus is known to form two kinds of cells on blood agar plates (coccoid and bacillary), evoking phase variation. 25736888 6 38 from abundant 1251:1258 arg1 saliva 1263:1268 saliva 1263:1268 saliva 1263:1268 Mucin, a heavily O-glycosylated protein abundant in saliva, also rescued growth and the shape of PUL5 mutant bacteria. 25736888 8 39 theme glycosidic 1504:1513 arg1 linkages 1515:1522 glycosidic linkages 1504:1522 peptide bonds of mucin rather than glycosidic linkages 1469:1522 Contrary to all known PUL-encoded systems, Muc cleaves peptide bonds of mucin rather than glycosidic linkages. 25736888 11 40 theme phase 1838:1842 arg1 variation 1844:1852 phase variation 1838:1852 phase variation 1838:1852 In vitro, it forms two kinds of cells (coccoid and bacillary), evoking phase variation. 25736888 5 41 theme acetyltransferase 987:1003 arg1 GlmU 1015:1018 GlmU 1015:1018 GlmU 1015:1018 Expression of the Escherichia coli GlmM together with the acetyltransferase domain of GlmU allowed PUL5 mutant bacteria to grow normally, indicating that C. canimorsus is a natural auxotroph that relies on GlcNAc harvested from the host N-glycoproteins for peptidoglycan synthesis. 25736888 5 41 theme acetyltransferase 987:1003 arg1 domain 1005:1010 the acetyltransferase domain 983:1010 the acetyltransferase domain of GlmU 983:1018 Expression of the Escherichia coli GlmM together with the acetyltransferase domain of GlmU allowed PUL5 mutant bacteria to grow normally, indicating that C. canimorsus is a natural auxotroph that relies on GlcNAc harvested from the host N-glycoproteins for peptidoglycan synthesis. 25736888 16 42 theme ecological 2600:2609 arg1 cavity 2627:2632 the oral cavity 2618:2632 the oral cavity of dogs 2618:2640 This study provides a molecular genetic demonstration for the complex adaptation of C. canimorsus to its ecological niche, the oral cavity of dogs. 25736888 16 42 theme ecological 2600:2609 arg1 niche 2611:2615 its ecological niche 2596:2615 its ecological niche 2596:2615 This study provides a molecular genetic demonstration for the complex adaptation of C. canimorsus to its ecological niche, the oral cavity of dogs. 25736888 3 43 theme wild-type 594:602 arg1 bacteria 604:611 wild-type bacteria 594:611 wild-type bacteria 594:611 Polysaccharide utilization locus 5 (PUL5) and sialidase mutant bacteria, unable to retrieve glycans from glycoproteins, grew less than wild-type bacteria and also appeared polymorphic unless GlcNAc was added, suggesting that C. canimorsus is unable to synthesize GlcNAc, an essential component of peptidoglycan. 25736888 10 44 dep Capnocytophaga 1643:1656 arg1 canimorsus 1658:1667 Capnocytophaga canimorsus 1643:1667 IMPORTANCE Capnocytophaga canimorsus 1632:1667 IMPORTANCE Capnocytophaga canimorsus is a bacterium that lives as a commensal in the dog mouth and causes severe infections in humans. 25736888 0 45 theme Capnocytophaga 49:62 arg1 canimorsus 64:73 Capnocytophaga canimorsus 49:73 Capnocytophaga canimorsus 49:73 Glycan-foraging systems reveal the adaptation of Capnocytophaga canimorsus to the dog mouth. 25736888 2 46 dep vancomycin 343:352 arg1 the 327:329 the 327:329 the 327:329 When grown in coculture with animal cells these bacteria appeared only as bacilli, but in the presence of vancomycin they were round, indicating that coccoid shapes likely result from weakening of the peptidoglycan layer. 25736888 2 46 dep vancomycin 343:352 arg1 presence 331:338 presence 331:338 presence 331:338 When grown in coculture with animal cells these bacteria appeared only as bacilli, but in the presence of vancomycin they were round, indicating that coccoid shapes likely result from weakening of the peptidoglycan layer. 25736888 6 47 from saliva 1263:1268 arg1 abundant 1251:1258 abundant 1251:1258 abundant 1251:1258 Mucin, a heavily O-glycosylated protein abundant in saliva, also rescued growth and the shape of PUL5 mutant bacteria. 25736888 5 48 theme GlmM 964:967 arg1 Expression 929:938 Expression 929:938 Expression of the Escherichia coli GlmM together with the acetyltransferase domain of GlmU 929:1018 Expression of the Escherichia coli GlmM together with the acetyltransferase domain of GlmU allowed PUL5 mutant bacteria to grow normally, indicating that C. canimorsus is a natural auxotroph that relies on GlcNAc harvested from the host N-glycoproteins for peptidoglycan synthesis. 25736888 11 49 theme cells 1799:1803 arg1 kinds 1790:1794 two kinds 1786:1794 two kinds of cells (coccoid and bacillary) 1786:1827 In vitro, it forms two kinds of cells (coccoid and bacillary), evoking phase variation. 25736888 14 50 theme utilization 2298:2308 arg1 system 2310:2315 the Bacteroides starch utilization system 2275:2315 the Bacteroides starch utilization system 2275:2315 In its niche, the dog mouth, C. canimorsus retrieves GlcNAc by foraging glycans from salivary mucin and N-linked glycoproteins through two different apparatuses, Muc and Gpd, both of which are related to the Bacteroides starch utilization system. 25736888 12 51 theme peptidoglycan 1925:1937 arg1 layer 1939:1943 the peptidoglycan layer 1921:1943 the peptidoglycan layer due to a shortage of N-acetylglucosamine (GlcNAc) 1921:1993 Here, we show that cell rounding likely results from weakening of the peptidoglycan layer due to a shortage of N-acetylglucosamine (GlcNAc). 25736888 16 52 theme genetic 2527:2533 arg1 demonstration 2535:2547 a molecular genetic demonstration 2515:2547 a molecular genetic demonstration for the complex adaptation of C. canimorsus to its ecological niche, the oral cavity of dogs 2515:2640 This study provides a molecular genetic demonstration for the complex adaptation of C. canimorsus to its ecological niche, the oral cavity of dogs. 25736888 14 53 theme Bacteroides 2279:2289 arg1 system 2310:2315 the Bacteroides starch utilization system 2275:2315 the Bacteroides starch utilization system 2275:2315 In its niche, the dog mouth, C. canimorsus retrieves GlcNAc by foraging glycans from salivary mucin and N-linked glycoproteins through two different apparatuses, Muc and Gpd, both of which are related to the Bacteroides starch utilization system. 25736888 3 54 theme utilization 474:484 arg1 PUL5 495:498 Polysaccharide utilization locus 5 (PUL5) and sialidase mutant bacteria 459:529 PUL5 495:498 Polysaccharide utilization locus 5 (PUL5) and sialidase mutant bacteria, unable to retrieve glycans from glycoproteins, grew less than wild-type bacteria and also appeared polymorphic unless GlcNAc was added, suggesting that C. canimorsus is unable to synthesize GlcNAc, an essential component of peptidoglycan. 25736888 9 55 gly glycoproteins 1617:1629 arg1 glycoproteins 1617:1629 the glycan-rich dog's mouth glycoproteins 1589:1629 the glycan-rich dog's mouth glycoproteins 1589:1629 Thus, C. canimorsus has adapted to build its peptidoglycan from the glycan-rich dog's mouth glycoproteins. 25736888 12 56 theme due 1945:1947 arg1 layer 1939:1943 the peptidoglycan layer 1921:1943 the peptidoglycan layer due to a shortage of N-acetylglucosamine (GlcNAc) 1921:1993 Here, we show that cell rounding likely results from weakening of the peptidoglycan layer due to a shortage of N-acetylglucosamine (GlcNAc). 25736888 2 57 theme animal 266:271 arg1 cells 273:277 animal cells 266:277 animal cells 266:277 When grown in coculture with animal cells these bacteria appeared only as bacilli, but in the presence of vancomycin they were round, indicating that coccoid shapes likely result from weakening of the peptidoglycan layer. 25736888 5 58 theme peptidoglycan 1186:1198 arg1 synthesis 1200:1208 peptidoglycan synthesis 1186:1208 peptidoglycan synthesis 1186:1208 Expression of the Escherichia coli GlmM together with the acetyltransferase domain of GlmU allowed PUL5 mutant bacteria to grow normally, indicating that C. canimorsus is a natural auxotroph that relies on GlcNAc harvested from the host N-glycoproteins for peptidoglycan synthesis. 25736888 9 59 theme mouth 1611:1615 arg1 glycoproteins 1617:1629 the glycan-rich dog's mouth glycoproteins 1589:1629 the glycan-rich dog's mouth glycoproteins 1589:1629 Thus, C. canimorsus has adapted to build its peptidoglycan from the glycan-rich dog's mouth glycoproteins. 25736888 14 60 theme dog 2089:2091 arg1 mouth 2093:2097 the dog mouth 2085:2097 the dog mouth 2085:2097 In its niche, the dog mouth, C. canimorsus retrieves GlcNAc by foraging glycans from salivary mucin and N-linked glycoproteins through two different apparatuses, Muc and Gpd, both of which are related to the Bacteroides starch utilization system. 25736888 14 60 theme dog 2089:2091 arg1 C. canimorsus 2100:2112 C. canimorsus 2100:2112 C. canimorsus 2100:2112 In its niche, the dog mouth, C. canimorsus retrieves GlcNAc by foraging glycans from salivary mucin and N-linked glycoproteins through two different apparatuses, Muc and Gpd, both of which are related to the Bacteroides starch utilization system. 25736888 6 61 theme abundant 1251:1258 arg1 protein 1243:1249 a heavily O-glycosylated protein 1218:1249 a heavily O-glycosylated protein abundant in saliva 1218:1268 Mucin, a heavily O-glycosylated protein abundant in saliva, also rescued growth and the shape of PUL5 mutant bacteria. 25736888 6 61 theme abundant 1251:1258 arg1 Mucin 1211:1215 Mucin 1211:1215 Mucin 1211:1215 Mucin, a heavily O-glycosylated protein abundant in saliva, also rescued growth and the shape of PUL5 mutant bacteria. 25736888 7 62 theme Sus-like 1381:1388 arg1 Muc 1374:1376 Muc 1374:1376 Muc 1374:1376 Utilization of mucin was found to depend on Muc, a Sus-like system encoded by PUL9. 25736888 7 62 theme Sus-like 1381:1388 arg1 system 1390:1395 a Sus-like system 1379:1395 a Sus-like system encoded by PUL9 1379:1411 Utilization of mucin was found to depend on Muc, a Sus-like system encoded by PUL9. 25736888 15 63 from peculiar 2336:2343 arg1 sense 2352:2356 the sense that the enzyme of the complex is a protease and not a glycosylhydrolase, as it cleaves peptide bonds in order to capture glycan chains 2348:2492 the sense that the enzyme of the complex is a protease and not a glycosylhydrolase, as it cleaves peptide bonds in order to capture glycan chains 2348:2492 The Muc system is peculiar in the sense that the enzyme of the complex is a protease and not a glycosylhydrolase, as it cleaves peptide bonds in order to capture glycan chains. 25736888 6 64 theme O-glycosylated 1228:1241 arg1 protein 1243:1249 a heavily O-glycosylated protein 1218:1249 a heavily O-glycosylated protein abundant in saliva 1218:1268 Mucin, a heavily O-glycosylated protein abundant in saliva, also rescued growth and the shape of PUL5 mutant bacteria. 25736888 6 64 theme O-glycosylated 1228:1241 arg1 Mucin 1211:1215 Mucin 1211:1215 Mucin 1211:1215 Mucin, a heavily O-glycosylated protein abundant in saliva, also rescued growth and the shape of PUL5 mutant bacteria. 25736888 10 65 theme severe 1738:1743 arg1 infections 1745:1754 severe infections 1738:1754 severe infections in humans 1738:1764 IMPORTANCE Capnocytophaga canimorsus is a bacterium that lives as a commensal in the dog mouth and causes severe infections in humans. 25736888 10 65 theme severe 1738:1743 arg1 commensal 1700:1708 a commensal 1698:1708 a commensal in the dog mouth 1698:1725 IMPORTANCE Capnocytophaga canimorsus is a bacterium that lives as a commensal in the dog mouth and causes severe infections in humans. 25736888 1 66 theme agar 175:178 arg1 plates 180:185 blood agar plates 169:185 blood agar plates (coccoid and bacillary) 169:209 UNLABELLED Capnocytophaga canimorsus is known to form two kinds of cells on blood agar plates (coccoid and bacillary), evoking phase variation. 25736888 12 67 theme cell 1874:1877 arg1 rounding 1879:1886 cell rounding 1874:1886 cell rounding 1874:1886 Here, we show that cell rounding likely results from weakening of the peptidoglycan layer due to a shortage of N-acetylglucosamine (GlcNAc). 25736888 3 68 gly glycoproteins 564:576 arg1 glycoproteins 564:576 glycoproteins 564:576 glycoproteins 564:576 Polysaccharide utilization locus 5 (PUL5) and sialidase mutant bacteria, unable to retrieve glycans from glycoproteins, grew less than wild-type bacteria and also appeared polymorphic unless GlcNAc was added, suggesting that C. canimorsus is unable to synthesize GlcNAc, an essential component of peptidoglycan. 25736888 6 69 theme mutant 1313:1318 arg1 bacteria 1320:1327 PUL5 mutant bacteria 1308:1327 PUL5 mutant bacteria 1308:1327 Mucin, a heavily O-glycosylated protein abundant in saliva, also rescued growth and the shape of PUL5 mutant bacteria. 25736888 4 70 theme genome 786:791 arg1 analysis 793:800 a genome analysis 784:800 a genome analysis 784:800 Accordingly, a genome analysis was conducted and revealed that C. canimorsus strain 5 lacks the GlmM and GlmU enzymes, which convert glucosamine into GlcNAc. 25736888 3 71 theme mutant 515:520 arg1 bacteria 522:529 Polysaccharide utilization locus 5 (PUL5) and sialidase mutant bacteria 459:529 bacteria 522:529 Polysaccharide utilization locus 5 (PUL5) and sialidase mutant bacteria, unable to retrieve glycans from glycoproteins, grew less than wild-type bacteria and also appeared polymorphic unless GlcNAc was added, suggesting that C. canimorsus is unable to synthesize GlcNAc, an essential component of peptidoglycan. 25736888 3 72 theme unable 532:537 arg1 PUL5 495:498 Polysaccharide utilization locus 5 (PUL5) and sialidase mutant bacteria 459:529 PUL5 495:498 Polysaccharide utilization locus 5 (PUL5) and sialidase mutant bacteria, unable to retrieve glycans from glycoproteins, grew less than wild-type bacteria and also appeared polymorphic unless GlcNAc was added, suggesting that C. canimorsus is unable to synthesize GlcNAc, an essential component of peptidoglycan. 25736888 4 73 theme GlmU 876:879 arg1 enzymes 881:887 the GlmM and GlmU enzymes 863:887 the GlmM and GlmU enzymes 863:887 Accordingly, a genome analysis was conducted and revealed that C. canimorsus strain 5 lacks the GlmM and GlmU enzymes, which convert glucosamine into GlcNAc. 25736888 16 74 theme oral 2622:2625 arg1 cavity 2627:2632 the oral cavity 2618:2632 the oral cavity of dogs 2618:2640 This study provides a molecular genetic demonstration for the complex adaptation of C. canimorsus to its ecological niche, the oral cavity of dogs. 25736888 16 74 theme oral 2622:2625 arg1 niche 2611:2615 its ecological niche 2596:2615 its ecological niche 2596:2615 This study provides a molecular genetic demonstration for the complex adaptation of C. canimorsus to its ecological niche, the oral cavity of dogs. 25736888 10 75 from commensal 1700:1708 arg1 mouth 1721:1725 the dog mouth 1713:1725 the dog mouth 1713:1725 IMPORTANCE Capnocytophaga canimorsus is a bacterium that lives as a commensal in the dog mouth and causes severe infections in humans. 25736888 2 76 with coculture 251:259 arg1 cells 273:277 animal cells 266:277 animal cells 266:277 When grown in coculture with animal cells these bacteria appeared only as bacilli, but in the presence of vancomycin they were round, indicating that coccoid shapes likely result from weakening of the peptidoglycan layer. 25736888 4 77 theme GlmM 867:870 arg1 enzymes 881:887 the GlmM and GlmU enzymes 863:887 the GlmM and GlmU enzymes 863:887 Accordingly, a genome analysis was conducted and revealed that C. canimorsus strain 5 lacks the GlmM and GlmU enzymes, which convert glucosamine into GlcNAc. 25736888 8 78 theme PUL-encoded 1436:1446 arg1 systems 1448:1454 all known PUL-encoded systems 1426:1454 all known PUL-encoded systems 1426:1454 Contrary to all known PUL-encoded systems, Muc cleaves peptide bonds of mucin rather than glycosidic linkages. 25736888 5 79 theme mutant 1033:1038 arg1 bacteria 1040:1047 PUL5 mutant bacteria 1028:1047 PUL5 mutant bacteria 1028:1047 Expression of the Escherichia coli GlmM together with the acetyltransferase domain of GlmU allowed PUL5 mutant bacteria to grow normally, indicating that C. canimorsus is a natural auxotroph that relies on GlcNAc harvested from the host N-glycoproteins for peptidoglycan synthesis. 25736888 3 80 theme peptidoglycan 756:768 arg1 GlcNAc 722:727 GlcNAc 722:727 GlcNAc 722:727 Polysaccharide utilization locus 5 (PUL5) and sialidase mutant bacteria, unable to retrieve glycans from glycoproteins, grew less than wild-type bacteria and also appeared polymorphic unless GlcNAc was added, suggesting that C. canimorsus is unable to synthesize GlcNAc, an essential component of peptidoglycan. 25736888 3 80 theme peptidoglycan 756:768 arg1 component 743:751 an essential component 730:751 an essential component of peptidoglycan 730:768 Polysaccharide utilization locus 5 (PUL5) and sialidase mutant bacteria, unable to retrieve glycans from glycoproteins, grew less than wild-type bacteria and also appeared polymorphic unless GlcNAc was added, suggesting that C. canimorsus is unable to synthesize GlcNAc, an essential component of peptidoglycan. 25736888 2 81 theme peptidoglycan 438:450 arg1 layer 452:456 the peptidoglycan layer 434:456 the peptidoglycan layer 434:456 When grown in coculture with animal cells these bacteria appeared only as bacilli, but in the presence of vancomycin they were round, indicating that coccoid shapes likely result from weakening of the peptidoglycan layer. 25736888 3 82 from glycoproteins 564:576 arg1 glycans 551:557 glycans 551:557 glycans from glycoproteins 551:576 Polysaccharide utilization locus 5 (PUL5) and sialidase mutant bacteria, unable to retrieve glycans from glycoproteins, grew less than wild-type bacteria and also appeared polymorphic unless GlcNAc was added, suggesting that C. canimorsus is unable to synthesize GlcNAc, an essential component of peptidoglycan. 25736888 10 83 from infections 1745:1754 arg1 humans 1759:1764 humans 1759:1764 humans 1759:1764 IMPORTANCE Capnocytophaga canimorsus is a bacterium that lives as a commensal in the dog mouth and causes severe infections in humans. 25736888 8 84 theme mucin 1486:1490 arg1 bonds 1477:1481 peptide bonds 1469:1481 peptide bonds of mucin rather than glycosidic linkages 1469:1522 Contrary to all known PUL-encoded systems, Muc cleaves peptide bonds of mucin rather than glycosidic linkages. 25736888 11 85 dep cells 1799:1803 arg1 bacillary 1818:1826 bacillary 1818:1826 bacillary 1818:1826 In vitro, it forms two kinds of cells (coccoid and bacillary), evoking phase variation. 25736888 11 85 dep cells 1799:1803 arg1 coccoid 1806:1812 coccoid 1806:1812 coccoid 1806:1812 In vitro, it forms two kinds of cells (coccoid and bacillary), evoking phase variation. 25736888 14 86 from glycoproteins 2184:2196 arg1 glycans 2143:2149 glycans 2143:2149 glycans from salivary mucin and N-linked glycoproteins 2143:2196 In its niche, the dog mouth, C. canimorsus retrieves GlcNAc by foraging glycans from salivary mucin and N-linked glycoproteins through two different apparatuses, Muc and Gpd, both of which are related to the Bacteroides starch utilization system. 25736888 14 87 theme salivary 2156:2163 arg1 mucin 2165:2169 salivary mucin and N-linked glycoproteins 2156:2196 mucin 2165:2169 In its niche, the dog mouth, C. canimorsus retrieves GlcNAc by foraging glycans from salivary mucin and N-linked glycoproteins through two different apparatuses, Muc and Gpd, both of which are related to the Bacteroides starch utilization system. 25736888 1 88 theme Capnocytophaga 104:117 arg1 canimorsus 119:128 UNLABELLED Capnocytophaga canimorsus 93:128 UNLABELLED Capnocytophaga canimorsus 93:128 UNLABELLED Capnocytophaga canimorsus is known to form two kinds of cells on blood agar plates (coccoid and bacillary), evoking phase variation. 25736888 2 89 theme coccoid 387:393 arg1 shapes 395:400 coccoid shapes 387:400 coccoid shapes 387:400 When grown in coculture with animal cells these bacteria appeared only as bacilli, but in the presence of vancomycin they were round, indicating that coccoid shapes likely result from weakening of the peptidoglycan layer. 25736888 5 90 theme host 1161:1164 arg1 N-glycoproteins 1166:1180 the host N-glycoproteins 1157:1180 the host N-glycoproteins for peptidoglycan synthesis 1157:1208 Expression of the Escherichia coli GlmM together with the acetyltransferase domain of GlmU allowed PUL5 mutant bacteria to grow normally, indicating that C. canimorsus is a natural auxotroph that relies on GlcNAc harvested from the host N-glycoproteins for peptidoglycan synthesis. 25736888 1 91 dep plates 180:185 arg1 coccoid 188:194 coccoid 188:194 coccoid 188:194 UNLABELLED Capnocytophaga canimorsus is known to form two kinds of cells on blood agar plates (coccoid and bacillary), evoking phase variation. 25736888 1 91 dep plates 180:185 arg1 bacillary 200:208 bacillary 200:208 bacillary 200:208 UNLABELLED Capnocytophaga canimorsus is known to form two kinds of cells on blood agar plates (coccoid and bacillary), evoking phase variation. 25736888 0 92 theme canimorsus 64:73 arg1 adaptation 35:44 the adaptation 31:44 the adaptation of Capnocytophaga canimorsus to the dog mouth 31:90 Glycan-foraging systems reveal the adaptation of Capnocytophaga canimorsus to the dog mouth. 25736888 10 93 dep IMPORTANCE 1632:1641 arg1 Capnocytophaga 1643:1656 Capnocytophaga 1643:1656 Capnocytophaga 1643:1656 IMPORTANCE Capnocytophaga canimorsus is a bacterium that lives as a commensal in the dog mouth and causes severe infections in humans. 25736888 3 94 theme Polysaccharide 459:472 arg1 PUL5 495:498 Polysaccharide utilization locus 5 (PUL5) and sialidase mutant bacteria 459:529 PUL5 495:498 Polysaccharide utilization locus 5 (PUL5) and sialidase mutant bacteria, unable to retrieve glycans from glycoproteins, grew less than wild-type bacteria and also appeared polymorphic unless GlcNAc was added, suggesting that C. canimorsus is unable to synthesize GlcNAc, an essential component of peptidoglycan. 25736888 15 95 theme peptide 2446:2452 arg1 bonds 2454:2458 peptide bonds 2446:2458 peptide bonds in order to capture glycan chains 2446:2492 The Muc system is peculiar in the sense that the enzyme of the complex is a protease and not a glycosylhydrolase, as it cleaves peptide bonds in order to capture glycan chains. 25736888 5 96 theme Escherichia coli 947:962 arg1 GlmM 964:967 the Escherichia coli GlmM 943:967 the Escherichia coli GlmM 943:967 Expression of the Escherichia coli GlmM together with the acetyltransferase domain of GlmU allowed PUL5 mutant bacteria to grow normally, indicating that C. canimorsus is a natural auxotroph that relies on GlcNAc harvested from the host N-glycoproteins for peptidoglycan synthesis. 25736888 16 97 theme molecular 2517:2525 arg1 demonstration 2535:2547 a molecular genetic demonstration 2515:2547 a molecular genetic demonstration for the complex adaptation of C. canimorsus to its ecological niche, the oral cavity of dogs 2515:2640 This study provides a molecular genetic demonstration for the complex adaptation of C. canimorsus to its ecological niche, the oral cavity of dogs. 25736888 12 98 theme layer 1939:1943 arg1 weakening 1908:1916 weakening 1908:1916 weakening of the peptidoglycan layer due to a shortage of N-acetylglucosamine (GlcNAc) 1908:1993 Here, we show that cell rounding likely results from weakening of the peptidoglycan layer due to a shortage of N-acetylglucosamine (GlcNAc). 25736888 16 99 theme complex 2557:2563 arg1 adaptation 2565:2574 the complex adaptation 2553:2574 the complex adaptation of C. canimorsus to its ecological niche, the oral cavity of dogs 2553:2640 This study provides a molecular genetic demonstration for the complex adaptation of C. canimorsus to its ecological niche, the oral cavity of dogs. 25736888 14 100 theme starch 2291:2296 arg1 system 2310:2315 the Bacteroides starch utilization system 2275:2315 the Bacteroides starch utilization system 2275:2315 In its niche, the dog mouth, C. canimorsus retrieves GlcNAc by foraging glycans from salivary mucin and N-linked glycoproteins through two different apparatuses, Muc and Gpd, both of which are related to the Bacteroides starch utilization system. 25736888 1 101 theme phase 220:224 arg1 variation 226:234 phase variation 220:234 phase variation 220:234 UNLABELLED Capnocytophaga canimorsus is known to form two kinds of cells on blood agar plates (coccoid and bacillary), evoking phase variation. 25518929 0 0 theme fibroblasts 100:110 arg1 analysis 28:35 Comparative N-linked glycan analysis 0:35 Comparative N-linked glycan analysis of wild-type and α1,3-galactosyltransferase gene knock-out pig fibroblasts 0:110 Comparative N-linked glycan analysis of wild-type and α1,3-galactosyltransferase gene knock-out pig fibroblasts using mass spectrometry approaches. 25518929 4 1 from fibroblasts 620:630 arg1 N-glycans 574:582 totally 47 N-glycans 563:582 totally 47 N-glycans from wild-type (WT) and GalT-KO pig fibroblasts 563:630 Here, we identified and quantified totally 47 N-glycans from wild-type (WT) and GalT-KO pig fibroblasts using mass spectrometry. 25518929 7 2 theme antigen 993:999 arg1 quantity 943:950 the relative quantity 930:950 the relative quantity of the N-glycolylneuraminic acid (NeuGc) antigen 930:999 Moreover, the relative quantity of the N-glycolylneuraminic acid (NeuGc) antigen is slightly higher in the GalT-KO pigs. 25518929 7 2 theme antigen 993:999 arg1 higher 1013:1018 higher 1013:1018 higher 1013:1018 Moreover, the relative quantity of the N-glycolylneuraminic acid (NeuGc) antigen is slightly higher in the GalT-KO pigs. 25518929 5 3 from residue 739:745 arg1 cells 766:770 the GalT-KO pig cells 750:770 the GalT-KO pig cells 750:770 First, our results confirmed the absence of galactose-alpha-1,3-galactose (α-Gal) residue in the GalT-KO pig cells. 25518929 0 4 theme pig 96:98 arg1 fibroblasts 100:110 wild-type and α1,3-galactosyltransferase gene knock-out pig fibroblasts 40:110 wild-type and α1,3-galactosyltransferase gene knock-out pig fibroblasts 40:110 Comparative N-linked glycan analysis of wild-type and α1,3-galactosyltransferase gene knock-out pig fibroblasts using mass spectrometry approaches. 25518929 6 5 theme N-glycans 836:844 arg1 level 807:811 the level 803:811 the level of overall fucosylated N-glycans from GalT-KO pig fibroblasts 803:873 Interestingly, we showed that the level of overall fucosylated N-glycans from GalT-KO pig fibroblasts is much higher than from WT pig fibroblasts. 25518929 6 5 theme N-glycans 836:844 arg1 higher 883:888 higher 883:888 higher 883:888 Interestingly, we showed that the level of overall fucosylated N-glycans from GalT-KO pig fibroblasts is much higher than from WT pig fibroblasts. 25518929 0 6 theme mass 118:121 arg1 approaches 136:145 mass spectrometry approaches 118:145 mass spectrometry approaches 118:145 Comparative N-linked glycan analysis of wild-type and α1,3-galactosyltransferase gene knock-out pig fibroblasts using mass spectrometry approaches. 25518929 8 7 from pigs 1142:1145 arg1 understanding 1086:1098 a better understanding 1077:1098 a better understanding of cellular glycan alterations on GalT-KO pigs for successful xenotransplantation 1077:1180 Thus, this study will contribute to a better understanding of cellular glycan alterations on GalT-KO pigs for successful xenotransplantation. 25518929 6 8 theme overall 816:822 arg1 N-glycans 836:844 overall fucosylated N-glycans 816:844 overall fucosylated N-glycans from GalT-KO pig fibroblasts 816:873 Interestingly, we showed that the level of overall fucosylated N-glycans from GalT-KO pig fibroblasts is much higher than from WT pig fibroblasts. 25518929 4 9 theme GalT-KO 608:614 arg1 fibroblasts 620:630 GalT-KO pig fibroblasts 608:630 GalT-KO pig fibroblasts 608:630 Here, we identified and quantified totally 47 N-glycans from wild-type (WT) and GalT-KO pig fibroblasts using mass spectrometry. 25518929 5 10 theme GalT-KO 754:760 arg1 cells 766:770 the GalT-KO pig cells 750:770 the GalT-KO pig cells 750:770 First, our results confirmed the absence of galactose-alpha-1,3-galactose (α-Gal) residue in the GalT-KO pig cells. 25518929 0 11 link N-linked 12:19 arg1 analysis 28:35 Comparative N-linked glycan analysis 0:35 Comparative N-linked glycan analysis of wild-type and α1,3-galactosyltransferase gene knock-out pig fibroblasts 0:110 Comparative N-linked glycan analysis of wild-type and α1,3-galactosyltransferase gene knock-out pig fibroblasts using mass spectrometry approaches. 25518929 5 12 theme pig 762:764 arg1 cells 766:770 the GalT-KO pig cells 750:770 the GalT-KO pig cells 750:770 First, our results confirmed the absence of galactose-alpha-1,3-galactose (α-Gal) residue in the GalT-KO pig cells. 25518929 4 13 dep wild-type 589:597 arg1 WT 600:601 WT 600:601 WT 600:601 Here, we identified and quantified totally 47 N-glycans from wild-type (WT) and GalT-KO pig fibroblasts using mass spectrometry. 25518929 7 14 theme acid 980:983 arg1 antigen 993:999 the N-glycolylneuraminic acid (NeuGc) antigen 955:999 the N-glycolylneuraminic acid (NeuGc) antigen 955:999 Moreover, the relative quantity of the N-glycolylneuraminic acid (NeuGc) antigen is slightly higher in the GalT-KO pigs. 25518929 0 15 theme spectrometry 123:134 arg1 approaches 136:145 mass spectrometry approaches 118:145 mass spectrometry approaches 118:145 Comparative N-linked glycan analysis of wild-type and α1,3-galactosyltransferase gene knock-out pig fibroblasts using mass spectrometry approaches. 25518929 6 16 theme WT 900:901 arg1 fibroblasts 907:917 WT pig fibroblasts 900:917 WT pig fibroblasts 900:917 Interestingly, we showed that the level of overall fucosylated N-glycans from GalT-KO pig fibroblasts is much higher than from WT pig fibroblasts. 25518929 8 17 from alterations 1119:1129 arg1 pigs 1142:1145 GalT-KO pigs 1134:1145 GalT-KO pigs for successful xenotransplantation 1134:1180 Thus, this study will contribute to a better understanding of cellular glycan alterations on GalT-KO pigs for successful xenotransplantation. 25518929 4 18 from wild-type 589:597 arg1 N-glycans 574:582 totally 47 N-glycans 563:582 totally 47 N-glycans from wild-type (WT) and GalT-KO pig fibroblasts 563:630 Here, we identified and quantified totally 47 N-glycans from wild-type (WT) and GalT-KO pig fibroblasts using mass spectrometry. 25518929 0 19 theme N-linked 12:19 arg1 analysis 28:35 Comparative N-linked glycan analysis 0:35 Comparative N-linked glycan analysis of wild-type and α1,3-galactosyltransferase gene knock-out pig fibroblasts 0:110 Comparative N-linked glycan analysis of wild-type and α1,3-galactosyltransferase gene knock-out pig fibroblasts using mass spectrometry approaches. 25518929 8 20 theme GalT-KO 1134:1140 arg1 pigs 1142:1145 GalT-KO pigs 1134:1145 GalT-KO pigs for successful xenotransplantation 1134:1180 Thus, this study will contribute to a better understanding of cellular glycan alterations on GalT-KO pigs for successful xenotransplantation. 25518929 6 21 theme pig 903:905 arg1 fibroblasts 907:917 WT pig fibroblasts 900:917 WT pig fibroblasts 900:917 Interestingly, we showed that the level of overall fucosylated N-glycans from GalT-KO pig fibroblasts is much higher than from WT pig fibroblasts. 25518929 0 22 theme Comparative 0:10 arg1 analysis 28:35 Comparative N-linked glycan analysis 0:35 Comparative N-linked glycan analysis of wild-type and α1,3-galactosyltransferase gene knock-out pig fibroblasts 0:110 Comparative N-linked glycan analysis of wild-type and α1,3-galactosyltransferase gene knock-out pig fibroblasts using mass spectrometry approaches. 25518929 7 23 theme relative 934:941 arg1 quantity 943:950 the relative quantity 930:950 the relative quantity of the N-glycolylneuraminic acid (NeuGc) antigen 930:999 Moreover, the relative quantity of the N-glycolylneuraminic acid (NeuGc) antigen is slightly higher in the GalT-KO pigs. 25518929 7 23 theme relative 934:941 arg1 higher 1013:1018 higher 1013:1018 higher 1013:1018 Moreover, the relative quantity of the N-glycolylneuraminic acid (NeuGc) antigen is slightly higher in the GalT-KO pigs. 25518929 2 24 theme non-Gal 359:365 arg1 antigens 367:374 potential non-Gal antigens 349:374 potential non-Gal antigens 349:374 Even after α1,3-galactosyltransferase gene knock-out (GalT-KO) pigs are generated, potential non-Gal antigens are still existed. 25518929 1 25 theme major 214:218 arg1 barriers 220:227 major barriers 214:227 major barriers 214:227 Carbohydrate antigens expressed on pig cells are considered to be major barriers in pig-to-human xenotransplantation. 25518929 6 26 from fibroblasts 863:873 arg1 level 807:811 the level 803:811 the level of overall fucosylated N-glycans from GalT-KO pig fibroblasts 803:873 Interestingly, we showed that the level of overall fucosylated N-glycans from GalT-KO pig fibroblasts is much higher than from WT pig fibroblasts. 25518929 6 26 from fibroblasts 863:873 arg1 higher 883:888 higher 883:888 higher 883:888 Interestingly, we showed that the level of overall fucosylated N-glycans from GalT-KO pig fibroblasts is much higher than from WT pig fibroblasts. 25518929 6 26 from fibroblasts 863:873 arg1 N-glycans 836:844 overall fucosylated N-glycans 816:844 overall fucosylated N-glycans from GalT-KO pig fibroblasts 816:873 Interestingly, we showed that the level of overall fucosylated N-glycans from GalT-KO pig fibroblasts is much higher than from WT pig fibroblasts. 25518929 7 27 theme N-glycolylneuraminic 959:978 arg1 acid 980:983 N-glycolylneuraminic acid 959:983 the N-glycolylneuraminic acid (NeuGc) antigen 955:999 Moreover, the relative quantity of the N-glycolylneuraminic acid (NeuGc) antigen is slightly higher in the GalT-KO pigs. 25518929 7 27 theme N-glycolylneuraminic 959:978 arg1 NeuGc 986:990 NeuGc 986:990 NeuGc 986:990 Moreover, the relative quantity of the N-glycolylneuraminic acid (NeuGc) antigen is slightly higher in the GalT-KO pigs. 25518929 5 28 theme α-Gal 732:736 arg1 residue 739:745 galactose-alpha-1,3-galactose (α-Gal) residue 701:745 galactose-alpha-1,3-galactose (α-Gal) residue in the GalT-KO pig cells 701:770 First, our results confirmed the absence of galactose-alpha-1,3-galactose (α-Gal) residue in the GalT-KO pig cells. 25518929 2 29 theme potential 349:357 arg1 antigens 367:374 potential non-Gal antigens 349:374 potential non-Gal antigens 349:374 Even after α1,3-galactosyltransferase gene knock-out (GalT-KO) pigs are generated, potential non-Gal antigens are still existed. 25518929 3 30 theme GalT-KO 498:504 arg1 pig 506:508 GalT-KO pig 498:508 the GalT-KO pig tissues 494:516 However, to the best of our knowledge there is no extensive study analyzing N-glycans expressed on the GalT-KO pig tissues or cells. 25518929 0 31 theme glycan 21:26 arg1 analysis 28:35 Comparative N-linked glycan analysis 0:35 Comparative N-linked glycan analysis of wild-type and α1,3-galactosyltransferase gene knock-out pig fibroblasts 0:110 Comparative N-linked glycan analysis of wild-type and α1,3-galactosyltransferase gene knock-out pig fibroblasts using mass spectrometry approaches. 25518929 3 32 theme pig 506:508 arg1 tissues 510:516 the GalT-KO pig tissues 494:516 the GalT-KO pig tissues 494:516 However, to the best of our knowledge there is no extensive study analyzing N-glycans expressed on the GalT-KO pig tissues or cells. 25518929 0 33 theme wild-type 40:48 arg1 fibroblasts 100:110 wild-type and α1,3-galactosyltransferase gene knock-out pig fibroblasts 40:110 wild-type and α1,3-galactosyltransferase gene knock-out pig fibroblasts 40:110 Comparative N-linked glycan analysis of wild-type and α1,3-galactosyltransferase gene knock-out pig fibroblasts using mass spectrometry approaches. 25518929 5 34 theme residue 739:745 arg1 absence 690:696 the absence 686:696 the absence of galactose-alpha-1,3-galactose (α-Gal) residue in the GalT-KO pig cells 686:770 First, our results confirmed the absence of galactose-alpha-1,3-galactose (α-Gal) residue in the GalT-KO pig cells. 25518929 5 35 from cells 766:770 arg1 absence 690:696 the absence 686:696 the absence of galactose-alpha-1,3-galactose (α-Gal) residue in the GalT-KO pig cells 686:770 First, our results confirmed the absence of galactose-alpha-1,3-galactose (α-Gal) residue in the GalT-KO pig cells. 25518929 2 36 theme α1,3-galactosyltransferase 277:302 arg1 knock-out 309:317 α1,3-galactosyltransferase gene knock-out 277:317 α1,3-galactosyltransferase gene knock-out (GalT-KO) pigs 277:332 Even after α1,3-galactosyltransferase gene knock-out (GalT-KO) pigs are generated, potential non-Gal antigens are still existed. 25518929 2 36 theme α1,3-galactosyltransferase 277:302 arg1 GalT-KO 320:326 GalT-KO 320:326 GalT-KO 320:326 Even after α1,3-galactosyltransferase gene knock-out (GalT-KO) pigs are generated, potential non-Gal antigens are still existed. 25518929 1 37 theme pig-to-human 232:243 arg1 xenotransplantation 245:263 pig-to-human xenotransplantation 232:263 pig-to-human xenotransplantation 232:263 Carbohydrate antigens expressed on pig cells are considered to be major barriers in pig-to-human xenotransplantation. 25518929 3 38 theme extensive 445:453 arg1 study 455:459 no extensive study 442:459 no extensive study analyzing N-glycans expressed on the GalT-KO pig tissues or cells 442:525 However, to the best of our knowledge there is no extensive study analyzing N-glycans expressed on the GalT-KO pig tissues or cells. 25518929 6 39 gly fucosylated 824:834 arg1 N-glycans 836:844 overall fucosylated N-glycans 816:844 overall fucosylated N-glycans from GalT-KO pig fibroblasts 816:873 Interestingly, we showed that the level of overall fucosylated N-glycans from GalT-KO pig fibroblasts is much higher than from WT pig fibroblasts. 25518929 8 40 theme better 1079:1084 arg1 understanding 1086:1098 a better understanding 1077:1098 a better understanding of cellular glycan alterations on GalT-KO pigs for successful xenotransplantation 1077:1180 Thus, this study will contribute to a better understanding of cellular glycan alterations on GalT-KO pigs for successful xenotransplantation. 25518929 5 41 from absence 690:696 arg1 cells 766:770 the GalT-KO pig cells 750:770 the GalT-KO pig cells 750:770 First, our results confirmed the absence of galactose-alpha-1,3-galactose (α-Gal) residue in the GalT-KO pig cells. 25518929 0 42 theme α1,3-galactosyltransferase 54:79 arg1 fibroblasts 100:110 wild-type and α1,3-galactosyltransferase gene knock-out pig fibroblasts 40:110 wild-type and α1,3-galactosyltransferase gene knock-out pig fibroblasts 40:110 Comparative N-linked glycan analysis of wild-type and α1,3-galactosyltransferase gene knock-out pig fibroblasts using mass spectrometry approaches. 25518929 8 43 theme cellular 1103:1110 arg1 alterations 1119:1129 cellular glycan alterations 1103:1129 cellular glycan alterations on GalT-KO pigs for successful xenotransplantation 1103:1180 Thus, this study will contribute to a better understanding of cellular glycan alterations on GalT-KO pigs for successful xenotransplantation. 25518929 7 44 theme GalT-KO 1027:1033 arg1 pigs 1035:1038 the GalT-KO pigs 1023:1038 the GalT-KO pigs 1023:1038 Moreover, the relative quantity of the N-glycolylneuraminic acid (NeuGc) antigen is slightly higher in the GalT-KO pigs. 25518929 1 45 from barriers 220:227 arg1 xenotransplantation 245:263 pig-to-human xenotransplantation 232:263 pig-to-human xenotransplantation 232:263 Carbohydrate antigens expressed on pig cells are considered to be major barriers in pig-to-human xenotransplantation. 25518929 1 46 theme Carbohydrate 148:159 arg1 antigens 161:168 Carbohydrate antigens 148:168 Carbohydrate antigens expressed on pig cells 148:191 Carbohydrate antigens expressed on pig cells are considered to be major barriers in pig-to-human xenotransplantation. 25518929 5 47 theme galactose-alpha-1,3-galactose 701:729 arg1 residue 739:745 galactose-alpha-1,3-galactose (α-Gal) residue 701:745 galactose-alpha-1,3-galactose (α-Gal) residue in the GalT-KO pig cells 701:770 First, our results confirmed the absence of galactose-alpha-1,3-galactose (α-Gal) residue in the GalT-KO pig cells. 25518929 6 48 theme pig 859:861 arg1 fibroblasts 863:873 GalT-KO pig fibroblasts 851:873 GalT-KO pig fibroblasts 851:873 Interestingly, we showed that the level of overall fucosylated N-glycans from GalT-KO pig fibroblasts is much higher than from WT pig fibroblasts. 25518929 6 49 theme fucosylated 824:834 arg1 N-glycans 836:844 overall fucosylated N-glycans 816:844 overall fucosylated N-glycans from GalT-KO pig fibroblasts 816:873 Interestingly, we showed that the level of overall fucosylated N-glycans from GalT-KO pig fibroblasts is much higher than from WT pig fibroblasts. 25518929 8 50 from understanding 1086:1098 arg1 pigs 1142:1145 GalT-KO pigs 1134:1145 GalT-KO pigs for successful xenotransplantation 1134:1180 Thus, this study will contribute to a better understanding of cellular glycan alterations on GalT-KO pigs for successful xenotransplantation. 25518929 8 51 theme glycan 1112:1117 arg1 alterations 1119:1129 cellular glycan alterations 1103:1129 cellular glycan alterations on GalT-KO pigs for successful xenotransplantation 1103:1180 Thus, this study will contribute to a better understanding of cellular glycan alterations on GalT-KO pigs for successful xenotransplantation. 25518929 6 52 theme GalT-KO 851:857 arg1 fibroblasts 863:873 GalT-KO pig fibroblasts 851:873 GalT-KO pig fibroblasts 851:873 Interestingly, we showed that the level of overall fucosylated N-glycans from GalT-KO pig fibroblasts is much higher than from WT pig fibroblasts. 25518929 8 53 theme alterations 1119:1129 arg1 understanding 1086:1098 a better understanding 1077:1098 a better understanding of cellular glycan alterations on GalT-KO pigs for successful xenotransplantation 1077:1180 Thus, this study will contribute to a better understanding of cellular glycan alterations on GalT-KO pigs for successful xenotransplantation. 25518929 4 54 theme pig 616:618 arg1 fibroblasts 620:630 GalT-KO pig fibroblasts 608:630 GalT-KO pig fibroblasts 608:630 Here, we identified and quantified totally 47 N-glycans from wild-type (WT) and GalT-KO pig fibroblasts using mass spectrometry. 25518929 0 55 theme knock-out 86:94 arg1 fibroblasts 100:110 wild-type and α1,3-galactosyltransferase gene knock-out pig fibroblasts 40:110 wild-type and α1,3-galactosyltransferase gene knock-out pig fibroblasts 40:110 Comparative N-linked glycan analysis of wild-type and α1,3-galactosyltransferase gene knock-out pig fibroblasts using mass spectrometry approaches. 25518929 2 56 theme knock-out 309:317 arg1 pigs 329:332 α1,3-galactosyltransferase gene knock-out (GalT-KO) pigs 277:332 α1,3-galactosyltransferase gene knock-out (GalT-KO) pigs 277:332 Even after α1,3-galactosyltransferase gene knock-out (GalT-KO) pigs are generated, potential non-Gal antigens are still existed. 25518929 4 57 theme mass 638:641 arg1 spectrometry 643:654 mass spectrometry 638:654 mass spectrometry 638:654 Here, we identified and quantified totally 47 N-glycans from wild-type (WT) and GalT-KO pig fibroblasts using mass spectrometry. 25518929 0 58 theme gene 81:84 arg1 fibroblasts 100:110 wild-type and α1,3-galactosyltransferase gene knock-out pig fibroblasts 40:110 wild-type and α1,3-galactosyltransferase gene knock-out pig fibroblasts 40:110 Comparative N-linked glycan analysis of wild-type and α1,3-galactosyltransferase gene knock-out pig fibroblasts using mass spectrometry approaches. 25518929 2 59 theme gene 304:307 arg1 knock-out 309:317 α1,3-galactosyltransferase gene knock-out 277:317 α1,3-galactosyltransferase gene knock-out (GalT-KO) pigs 277:332 Even after α1,3-galactosyltransferase gene knock-out (GalT-KO) pigs are generated, potential non-Gal antigens are still existed. 25518929 2 59 theme gene 304:307 arg1 GalT-KO 320:326 GalT-KO 320:326 GalT-KO 320:326 Even after α1,3-galactosyltransferase gene knock-out (GalT-KO) pigs are generated, potential non-Gal antigens are still existed. 25518929 6 60 from level 807:811 arg1 fibroblasts 863:873 GalT-KO pig fibroblasts 851:873 GalT-KO pig fibroblasts 851:873 Interestingly, we showed that the level of overall fucosylated N-glycans from GalT-KO pig fibroblasts is much higher than from WT pig fibroblasts. 25518929 1 61 theme pig 183:185 arg1 cells 187:191 pig cells 183:191 pig cells 183:191 Carbohydrate antigens expressed on pig cells are considered to be major barriers in pig-to-human xenotransplantation. 25518929 8 62 theme successful 1151:1160 arg1 xenotransplantation 1162:1180 successful xenotransplantation 1151:1180 successful xenotransplantation 1151:1180 Thus, this study will contribute to a better understanding of cellular glycan alterations on GalT-KO pigs for successful xenotransplantation. 25486605 8 0 theme membrane 1632:1639 arg1 proteins 1641:1648 properly folded polytopic membrane proteins 1606:1648 properly folded polytopic membrane proteins as well as tail-anchored proteins 1606:1682 These results showed that the newly developed cell-free translocation system derived from cultured insect cells is a practical tool for the biogenesis of properly folded polytopic membrane proteins as well as tail-anchored proteins. 25486605 8 1 theme developed 1488:1496 arg1 system 1522:1527 the newly developed cell-free translocation system 1478:1527 the newly developed cell-free translocation system derived from cultured insect cells 1478:1562 These results showed that the newly developed cell-free translocation system derived from cultured insect cells is a practical tool for the biogenesis of properly folded polytopic membrane proteins as well as tail-anchored proteins. 25486605 8 1 theme developed 1488:1496 arg1 tool 1579:1582 a practical tool 1567:1582 a practical tool for the biogenesis of properly folded polytopic membrane proteins as well as tail-anchored proteins 1567:1682 These results showed that the newly developed cell-free translocation system derived from cultured insect cells is a practical tool for the biogenesis of properly folded polytopic membrane proteins as well as tail-anchored proteins. 25486605 4 2 theme polytopic 793:801 arg1 apparatus 935:943 the apparatus 931:943 the apparatus for signal peptide cleavage and N-linked glycosylation 931:998 The isolated microsomes contained the basic translocation machinery for polytopic membrane proteins including SRP-dependent targeting components, translocation channel (translocon)-dependent translocation, and the apparatus for signal peptide cleavage and N-linked glycosylation. 25486605 4 2 theme polytopic 793:801 arg1 proteins 812:819 polytopic membrane proteins 793:819 polytopic membrane proteins including SRP-dependent targeting components, translocation channel (translocon)-dependent translocation, and the apparatus for signal peptide cleavage and N-linked glycosylation 793:998 The isolated microsomes contained the basic translocation machinery for polytopic membrane proteins including SRP-dependent targeting components, translocation channel (translocon)-dependent translocation, and the apparatus for signal peptide cleavage and N-linked glycosylation. 25486605 4 2 theme polytopic 793:801 arg1 translocation 912:924 translocation channel (translocon)-dependent translocation 867:924 translocation channel (translocon)-dependent translocation 867:924 The isolated microsomes contained the basic translocation machinery for polytopic membrane proteins including SRP-dependent targeting components, translocation channel (translocon)-dependent translocation, and the apparatus for signal peptide cleavage and N-linked glycosylation. 25486605 4 2 theme polytopic 793:801 arg1 components 855:864 SRP-dependent targeting components 831:864 SRP-dependent targeting components 831:864 The isolated microsomes contained the basic translocation machinery for polytopic membrane proteins including SRP-dependent targeting components, translocation channel (translocon)-dependent translocation, and the apparatus for signal peptide cleavage and N-linked glycosylation. 25486605 2 3 theme living 471:476 arg1 animals 478:484 living animals 471:484 living animals 471:484 Developing a cell-free system based on cultured cells for the synthesis of membrane proteins could provide a highly reproducible alternative to the use of tissues from living animals. 25486605 3 4 theme cell-free 658:666 arg1 system 680:685 a cell-free translation system 656:685 a cell-free translation system originating from the same source 656:718 We isolated Sf21 microsomes from cultured insect cells by a simplified isolation procedure and evaluated the performance of the translocation system in combination with a cell-free translation system originating from the same source. 25486605 6 5 theme non-natural 1164:1174 arg1 acids 1182:1186 non-natural amino acids 1164:1186 non-natural amino acids 1164:1186 In addition, single and double labeling with non-natural amino acids could be achieved at both the lumen side and the cytosolic side in this system. 25486605 2 6 theme cultured 342:349 arg1 cells 351:355 cultured cells 342:355 cultured cells for the synthesis of membrane proteins 342:394 Developing a cell-free system based on cultured cells for the synthesis of membrane proteins could provide a highly reproducible alternative to the use of tissues from living animals. 25486605 3 7 from cells 536:540 arg1 microsomes 504:513 Sf21 microsomes 499:513 Sf21 microsomes from cultured insect cells 499:540 We isolated Sf21 microsomes from cultured insect cells by a simplified isolation procedure and evaluated the performance of the translocation system in combination with a cell-free translation system originating from the same source. 25486605 5 8 theme cell-free 1044:1052 arg1 system 1054:1059 the cell-free system 1040:1059 the cell-free system 1040:1059 A transporter protein synthesized with the cell-free system could be functionally reconstituted into a lipid bilayer. 25486605 0 9 theme membrane 93:100 arg1 proteins 102:109 functional membrane proteins 82:109 functional membrane proteins 82:109 A cell-free translocation system using extracts of cultured insect cells to yield functional membrane proteins. 25486605 4 10 theme SRP-dependent 831:843 arg1 components 855:864 SRP-dependent targeting components 831:864 SRP-dependent targeting components 831:864 The isolated microsomes contained the basic translocation machinery for polytopic membrane proteins including SRP-dependent targeting components, translocation channel (translocon)-dependent translocation, and the apparatus for signal peptide cleavage and N-linked glycosylation. 25486605 6 11 theme cytosolic 1237:1245 arg1 side 1247:1250 the cytosolic side 1233:1250 the cytosolic side 1233:1250 In addition, single and double labeling with non-natural amino acids could be achieved at both the lumen side and the cytosolic side in this system. 25486605 3 12 theme simplified 547:556 arg1 procedure 568:576 a simplified isolation procedure 545:576 a simplified isolation procedure 545:576 We isolated Sf21 microsomes from cultured insect cells by a simplified isolation procedure and evaluated the performance of the translocation system in combination with a cell-free translation system originating from the same source. 25486605 8 13 theme polytopic 1622:1630 arg1 proteins 1641:1648 properly folded polytopic membrane proteins 1606:1648 properly folded polytopic membrane proteins as well as tail-anchored proteins 1606:1682 These results showed that the newly developed cell-free translocation system derived from cultured insect cells is a practical tool for the biogenesis of properly folded polytopic membrane proteins as well as tail-anchored proteins. 25486605 0 14 theme functional 82:91 arg1 proteins 102:109 functional membrane proteins 82:109 functional membrane proteins 82:109 A cell-free translocation system using extracts of cultured insect cells to yield functional membrane proteins. 25486605 4 15 theme isolated 725:732 arg1 microsomes 734:743 The isolated microsomes 721:743 The isolated microsomes 721:743 The isolated microsomes contained the basic translocation machinery for polytopic membrane proteins including SRP-dependent targeting components, translocation channel (translocon)-dependent translocation, and the apparatus for signal peptide cleavage and N-linked glycosylation. 25486605 2 16 from use 451:453 arg1 animals 478:484 living animals 471:484 living animals 471:484 Developing a cell-free system based on cultured cells for the synthesis of membrane proteins could provide a highly reproducible alternative to the use of tissues from living animals. 25486605 6 17 theme double 1143:1148 arg1 labeling 1150:1157 single and double labeling 1132:1157 single and double labeling with non-natural amino acids 1132:1186 In addition, single and double labeling with non-natural amino acids could be achieved at both the lumen side and the cytosolic side in this system. 25486605 3 18 theme cultured 520:527 arg1 cells 536:540 cultured insect cells 520:540 cultured insect cells 520:540 We isolated Sf21 microsomes from cultured insect cells by a simplified isolation procedure and evaluated the performance of the translocation system in combination with a cell-free translation system originating from the same source. 25486605 7 19 theme proteins 1381:1388 arg1 machinery 1396:1404 tail-anchored proteins (GET) machinery 1367:1404 tail-anchored proteins (GET) machinery 1367:1404 Moreover, tail-anchored proteins, which are post-translationally integrated by the guided entry of tail-anchored proteins (GET) machinery, were inserted correctly into the microsomes. 25486605 2 20 theme proteins 387:394 arg1 synthesis 365:373 the synthesis 361:373 the synthesis of membrane proteins 361:394 Developing a cell-free system based on cultured cells for the synthesis of membrane proteins could provide a highly reproducible alternative to the use of tissues from living animals. 25486605 3 21 theme insect 529:534 arg1 cells 536:540 cultured insect cells 520:540 cultured insect cells 520:540 We isolated Sf21 microsomes from cultured insect cells by a simplified isolation procedure and evaluated the performance of the translocation system in combination with a cell-free translation system originating from the same source. 25486605 2 22 theme membrane 378:385 arg1 proteins 387:394 membrane proteins 378:394 membrane proteins 378:394 Developing a cell-free system based on cultured cells for the synthesis of membrane proteins could provide a highly reproducible alternative to the use of tissues from living animals. 25486605 0 23 theme cell-free 2:10 arg1 system 26:31 A cell-free translocation system 0:31 A cell-free translocation system using extracts of cultured insect cells 0:71 A cell-free translocation system using extracts of cultured insect cells to yield functional membrane proteins. 25486605 6 24 theme lumen 1218:1222 arg1 side 1224:1227 the lumen side 1214:1227 the lumen side 1214:1227 In addition, single and double labeling with non-natural amino acids could be achieved at both the lumen side and the cytosolic side in this system. 25486605 4 25 theme -dependent 901:910 arg1 translocation 912:924 translocation channel (translocon)-dependent translocation 867:924 translocation channel (translocon)-dependent translocation 867:924 The isolated microsomes contained the basic translocation machinery for polytopic membrane proteins including SRP-dependent targeting components, translocation channel (translocon)-dependent translocation, and the apparatus for signal peptide cleavage and N-linked glycosylation. 25486605 8 26 theme folded 1615:1620 arg1 proteins 1641:1648 properly folded polytopic membrane proteins 1606:1648 properly folded polytopic membrane proteins as well as tail-anchored proteins 1606:1682 These results showed that the newly developed cell-free translocation system derived from cultured insect cells is a practical tool for the biogenesis of properly folded polytopic membrane proteins as well as tail-anchored proteins. 25486605 1 27 dep method 154:159 arg1 analyze 227:233 analyze 227:233 to analyze the targeting and translocation of proteins across the ER membrane 224:300 Cell-free protein synthesis is a powerful method to explore the structure and function of membrane proteins and to analyze the targeting and translocation of proteins across the ER membrane. 25486605 1 27 dep method 154:159 arg1 explore 164:170 explore 164:170 to explore the structure and function of membrane proteins 161:218 Cell-free protein synthesis is a powerful method to explore the structure and function of membrane proteins and to analyze the targeting and translocation of proteins across the ER membrane. 25486605 6 28 with labeling 1150:1157 arg1 acids 1182:1186 non-natural amino acids 1164:1186 non-natural amino acids 1164:1186 In addition, single and double labeling with non-natural amino acids could be achieved at both the lumen side and the cytosolic side in this system. 25486605 6 29 theme single 1132:1137 arg1 labeling 1150:1157 single and double labeling 1132:1157 single and double labeling with non-natural amino acids 1132:1186 In addition, single and double labeling with non-natural amino acids could be achieved at both the lumen side and the cytosolic side in this system. 25486605 1 30 theme proteins 270:277 arg1 translocation 253:265 translocation 253:265 translocation 253:265 Cell-free protein synthesis is a powerful method to explore the structure and function of membrane proteins and to analyze the targeting and translocation of proteins across the ER membrane. 25486605 1 30 theme proteins 270:277 arg1 targeting 239:247 targeting 239:247 targeting 239:247 Cell-free protein synthesis is a powerful method to explore the structure and function of membrane proteins and to analyze the targeting and translocation of proteins across the ER membrane. 25486605 8 31 theme insect 1551:1556 arg1 cells 1558:1562 cultured insect cells 1542:1562 cultured insect cells 1542:1562 These results showed that the newly developed cell-free translocation system derived from cultured insect cells is a practical tool for the biogenesis of properly folded polytopic membrane proteins as well as tail-anchored proteins. 25486605 7 32 theme tail-anchored 1278:1290 arg1 proteins 1292:1299 tail-anchored proteins 1278:1299 tail-anchored proteins 1278:1299 Moreover, tail-anchored proteins, which are post-translationally integrated by the guided entry of tail-anchored proteins (GET) machinery, were inserted correctly into the microsomes. 25486605 8 33 theme cell-free 1498:1506 arg1 system 1522:1527 the newly developed cell-free translocation system 1478:1527 the newly developed cell-free translocation system derived from cultured insect cells 1478:1562 These results showed that the newly developed cell-free translocation system derived from cultured insect cells is a practical tool for the biogenesis of properly folded polytopic membrane proteins as well as tail-anchored proteins. 25486605 8 33 theme cell-free 1498:1506 arg1 tool 1579:1582 a practical tool 1567:1582 a practical tool for the biogenesis of properly folded polytopic membrane proteins as well as tail-anchored proteins 1567:1682 These results showed that the newly developed cell-free translocation system derived from cultured insect cells is a practical tool for the biogenesis of properly folded polytopic membrane proteins as well as tail-anchored proteins. 25486605 7 34 theme machinery 1396:1404 arg1 entry 1358:1362 the guided entry 1347:1362 the guided entry of tail-anchored proteins (GET) machinery 1347:1404 Moreover, tail-anchored proteins, which are post-translationally integrated by the guided entry of tail-anchored proteins (GET) machinery, were inserted correctly into the microsomes. 25486605 5 35 theme lipid 1104:1108 arg1 bilayer 1110:1116 a lipid bilayer 1102:1116 a lipid bilayer 1102:1116 A transporter protein synthesized with the cell-free system could be functionally reconstituted into a lipid bilayer. 25486605 4 36 theme translocation 765:777 arg1 machinery 779:787 the basic translocation machinery 755:787 the basic translocation machinery for polytopic membrane proteins including SRP-dependent targeting components, translocation channel (translocon)-dependent translocation, and the apparatus for signal peptide cleavage and N-linked glycosylation 755:998 The isolated microsomes contained the basic translocation machinery for polytopic membrane proteins including SRP-dependent targeting components, translocation channel (translocon)-dependent translocation, and the apparatus for signal peptide cleavage and N-linked glycosylation. 25486605 3 37 with combination 639:649 arg1 system 680:685 a cell-free translation system 656:685 a cell-free translation system originating from the same source 656:718 We isolated Sf21 microsomes from cultured insect cells by a simplified isolation procedure and evaluated the performance of the translocation system in combination with a cell-free translation system originating from the same source. 25486605 2 38 theme reproducible 419:430 arg1 alternative 432:442 a highly reproducible alternative 410:442 a highly reproducible alternative to the use of tissues from living animals 410:484 Developing a cell-free system based on cultured cells for the synthesis of membrane proteins could provide a highly reproducible alternative to the use of tissues from living animals. 25486605 4 39 contain contained 745:753 arg2 machinery 779:787 the basic translocation machinery 755:787 the basic translocation machinery for polytopic membrane proteins including SRP-dependent targeting components, translocation channel (translocon)-dependent translocation, and the apparatus for signal peptide cleavage and N-linked glycosylation 755:998 The isolated microsomes contained the basic translocation machinery for polytopic membrane proteins including SRP-dependent targeting components, translocation channel (translocon)-dependent translocation, and the apparatus for signal peptide cleavage and N-linked glycosylation. 25486605 4 39 contain contained 745:753 arg1 microsomes 734:743 The isolated microsomes 721:743 The isolated microsomes 721:743 The isolated microsomes contained the basic translocation machinery for polytopic membrane proteins including SRP-dependent targeting components, translocation channel (translocon)-dependent translocation, and the apparatus for signal peptide cleavage and N-linked glycosylation. 25486605 4 40 theme membrane 803:810 arg1 apparatus 935:943 the apparatus 931:943 the apparatus for signal peptide cleavage and N-linked glycosylation 931:998 The isolated microsomes contained the basic translocation machinery for polytopic membrane proteins including SRP-dependent targeting components, translocation channel (translocon)-dependent translocation, and the apparatus for signal peptide cleavage and N-linked glycosylation. 25486605 4 40 theme membrane 803:810 arg1 proteins 812:819 polytopic membrane proteins 793:819 polytopic membrane proteins including SRP-dependent targeting components, translocation channel (translocon)-dependent translocation, and the apparatus for signal peptide cleavage and N-linked glycosylation 793:998 The isolated microsomes contained the basic translocation machinery for polytopic membrane proteins including SRP-dependent targeting components, translocation channel (translocon)-dependent translocation, and the apparatus for signal peptide cleavage and N-linked glycosylation. 25486605 4 40 theme membrane 803:810 arg1 translocation 912:924 translocation channel (translocon)-dependent translocation 867:924 translocation channel (translocon)-dependent translocation 867:924 The isolated microsomes contained the basic translocation machinery for polytopic membrane proteins including SRP-dependent targeting components, translocation channel (translocon)-dependent translocation, and the apparatus for signal peptide cleavage and N-linked glycosylation. 25486605 4 40 theme membrane 803:810 arg1 components 855:864 SRP-dependent targeting components 831:864 SRP-dependent targeting components 831:864 The isolated microsomes contained the basic translocation machinery for polytopic membrane proteins including SRP-dependent targeting components, translocation channel (translocon)-dependent translocation, and the apparatus for signal peptide cleavage and N-linked glycosylation. 25486605 2 41 from animals 478:484 arg1 tissues 458:464 tissues 458:464 tissues from living animals 458:484 Developing a cell-free system based on cultured cells for the synthesis of membrane proteins could provide a highly reproducible alternative to the use of tissues from living animals. 25486605 2 41 from animals 478:484 arg1 use 451:453 the use 447:453 the use of tissues from living animals 447:484 Developing a cell-free system based on cultured cells for the synthesis of membrane proteins could provide a highly reproducible alternative to the use of tissues from living animals. 25486605 3 42 theme Sf21 499:502 arg1 microsomes 504:513 Sf21 microsomes 499:513 Sf21 microsomes from cultured insect cells 499:540 We isolated Sf21 microsomes from cultured insect cells by a simplified isolation procedure and evaluated the performance of the translocation system in combination with a cell-free translation system originating from the same source. 25486605 7 43 theme tail-anchored 1367:1379 arg1 proteins 1381:1388 tail-anchored proteins 1367:1388 tail-anchored proteins (GET) machinery 1367:1404 Moreover, tail-anchored proteins, which are post-translationally integrated by the guided entry of tail-anchored proteins (GET) machinery, were inserted correctly into the microsomes. 25486605 1 44 theme ER 290:291 arg1 membrane 293:300 the ER membrane 286:300 the ER membrane 286:300 Cell-free protein synthesis is a powerful method to explore the structure and function of membrane proteins and to analyze the targeting and translocation of proteins across the ER membrane. 25486605 7 45 theme guided 1351:1356 arg1 entry 1358:1362 the guided entry 1347:1362 the guided entry of tail-anchored proteins (GET) machinery 1347:1404 Moreover, tail-anchored proteins, which are post-translationally integrated by the guided entry of tail-anchored proteins (GET) machinery, were inserted correctly into the microsomes. 25486605 1 46 dep structure 176:184 arg1 the 172:174 the 172:174 the 172:174 Cell-free protein synthesis is a powerful method to explore the structure and function of membrane proteins and to analyze the targeting and translocation of proteins across the ER membrane. 25486605 8 47 attach derived 1529:1535 arg1 cells 1558:1562 cultured insect cells 1542:1562 cultured insect cells 1542:1562 These results showed that the newly developed cell-free translocation system derived from cultured insect cells is a practical tool for the biogenesis of properly folded polytopic membrane proteins as well as tail-anchored proteins. 25486605 8 47 attach derived 1529:1535 arg2 tool 1579:1582 a practical tool 1567:1582 a practical tool for the biogenesis of properly folded polytopic membrane proteins as well as tail-anchored proteins 1567:1682 These results showed that the newly developed cell-free translocation system derived from cultured insect cells is a practical tool for the biogenesis of properly folded polytopic membrane proteins as well as tail-anchored proteins. 25486605 8 47 attach derived 1529:1535 arg2 system 1522:1527 the newly developed cell-free translocation system 1478:1527 the newly developed cell-free translocation system derived from cultured insect cells 1478:1562 These results showed that the newly developed cell-free translocation system derived from cultured insect cells is a practical tool for the biogenesis of properly folded polytopic membrane proteins as well as tail-anchored proteins. 25486605 1 48 theme membrane 202:209 arg1 proteins 211:218 membrane proteins 202:218 membrane proteins 202:218 Cell-free protein synthesis is a powerful method to explore the structure and function of membrane proteins and to analyze the targeting and translocation of proteins across the ER membrane. 25486605 2 49 theme tissues 458:464 arg1 use 451:453 the use 447:453 the use of tissues from living animals 447:484 Developing a cell-free system based on cultured cells for the synthesis of membrane proteins could provide a highly reproducible alternative to the use of tissues from living animals. 25486605 4 50 theme N-linked 977:984 arg1 glycosylation 986:998 N-linked glycosylation 977:998 N-linked glycosylation 977:998 The isolated microsomes contained the basic translocation machinery for polytopic membrane proteins including SRP-dependent targeting components, translocation channel (translocon)-dependent translocation, and the apparatus for signal peptide cleavage and N-linked glycosylation. 25486605 8 51 theme translocation 1508:1520 arg1 system 1522:1527 the newly developed cell-free translocation system 1478:1527 the newly developed cell-free translocation system derived from cultured insect cells 1478:1562 These results showed that the newly developed cell-free translocation system derived from cultured insect cells is a practical tool for the biogenesis of properly folded polytopic membrane proteins as well as tail-anchored proteins. 25486605 8 51 theme translocation 1508:1520 arg1 tool 1579:1582 a practical tool 1567:1582 a practical tool for the biogenesis of properly folded polytopic membrane proteins as well as tail-anchored proteins 1567:1682 These results showed that the newly developed cell-free translocation system derived from cultured insect cells is a practical tool for the biogenesis of properly folded polytopic membrane proteins as well as tail-anchored proteins. 25486605 1 52 theme proteins 211:218 arg1 structure 176:184 structure 176:184 structure 176:184 Cell-free protein synthesis is a powerful method to explore the structure and function of membrane proteins and to analyze the targeting and translocation of proteins across the ER membrane. 25486605 1 52 theme proteins 211:218 arg1 function 190:197 function 190:197 function 190:197 Cell-free protein synthesis is a powerful method to explore the structure and function of membrane proteins and to analyze the targeting and translocation of proteins across the ER membrane. 25486605 0 53 theme cultured 51:58 arg1 cells 67:71 cultured insect cells 51:71 cultured insect cells 51:71 A cell-free translocation system using extracts of cultured insect cells to yield functional membrane proteins. 25486605 8 54 theme proteins 1641:1648 arg1 biogenesis 1592:1601 the biogenesis 1588:1601 the biogenesis of properly folded polytopic membrane proteins as well as tail-anchored proteins 1588:1682 These results showed that the newly developed cell-free translocation system derived from cultured insect cells is a practical tool for the biogenesis of properly folded polytopic membrane proteins as well as tail-anchored proteins. 25486605 4 55 link N-linked 977:984 arg1 glycosylation 986:998 N-linked glycosylation 977:998 N-linked glycosylation 977:998 The isolated microsomes contained the basic translocation machinery for polytopic membrane proteins including SRP-dependent targeting components, translocation channel (translocon)-dependent translocation, and the apparatus for signal peptide cleavage and N-linked glycosylation. 25486605 1 56 theme Cell-free 112:120 arg1 synthesis 130:138 Cell-free protein synthesis 112:138 Cell-free protein synthesis 112:138 Cell-free protein synthesis is a powerful method to explore the structure and function of membrane proteins and to analyze the targeting and translocation of proteins across the ER membrane. 25486605 1 56 theme Cell-free 112:120 arg1 method 154:159 a powerful method 143:159 a powerful method to explore the structure and function of membrane proteins and to analyze the targeting and translocation of proteins across the ER membrane 143:300 Cell-free protein synthesis is a powerful method to explore the structure and function of membrane proteins and to analyze the targeting and translocation of proteins across the ER membrane. 25486605 8 57 theme practical 1569:1577 arg1 system 1522:1527 the newly developed cell-free translocation system 1478:1527 the newly developed cell-free translocation system derived from cultured insect cells 1478:1562 These results showed that the newly developed cell-free translocation system derived from cultured insect cells is a practical tool for the biogenesis of properly folded polytopic membrane proteins as well as tail-anchored proteins. 25486605 8 57 theme practical 1569:1577 arg1 tool 1579:1582 a practical tool 1567:1582 a practical tool for the biogenesis of properly folded polytopic membrane proteins as well as tail-anchored proteins 1567:1682 These results showed that the newly developed cell-free translocation system derived from cultured insect cells is a practical tool for the biogenesis of properly folded polytopic membrane proteins as well as tail-anchored proteins. 25486605 8 58 theme cultured 1542:1549 arg1 cells 1558:1562 cultured insect cells 1542:1562 cultured insect cells 1542:1562 These results showed that the newly developed cell-free translocation system derived from cultured insect cells is a practical tool for the biogenesis of properly folded polytopic membrane proteins as well as tail-anchored proteins. 25486605 4 59 theme translocation 867:879 arg1 channel 881:887 translocation channel 867:887 translocation channel 867:887 The isolated microsomes contained the basic translocation machinery for polytopic membrane proteins including SRP-dependent targeting components, translocation channel (translocon)-dependent translocation, and the apparatus for signal peptide cleavage and N-linked glycosylation. 25486605 7 60 dep proteins 1381:1388 arg1 GET 1391:1393 GET 1391:1393 GET 1391:1393 Moreover, tail-anchored proteins, which are post-translationally integrated by the guided entry of tail-anchored proteins (GET) machinery, were inserted correctly into the microsomes. 25486605 1 61 theme protein 122:128 arg1 synthesis 130:138 Cell-free protein synthesis 112:138 Cell-free protein synthesis 112:138 Cell-free protein synthesis is a powerful method to explore the structure and function of membrane proteins and to analyze the targeting and translocation of proteins across the ER membrane. 25486605 1 61 theme protein 122:128 arg1 method 154:159 a powerful method 143:159 a powerful method to explore the structure and function of membrane proteins and to analyze the targeting and translocation of proteins across the ER membrane 143:300 Cell-free protein synthesis is a powerful method to explore the structure and function of membrane proteins and to analyze the targeting and translocation of proteins across the ER membrane. 25486605 3 62 theme isolation 558:566 arg1 procedure 568:576 a simplified isolation procedure 545:576 a simplified isolation procedure 545:576 We isolated Sf21 microsomes from cultured insect cells by a simplified isolation procedure and evaluated the performance of the translocation system in combination with a cell-free translation system originating from the same source. 25486605 4 63 theme peptide 956:962 arg1 cleavage 964:971 signal peptide cleavage 949:971 signal peptide cleavage 949:971 The isolated microsomes contained the basic translocation machinery for polytopic membrane proteins including SRP-dependent targeting components, translocation channel (translocon)-dependent translocation, and the apparatus for signal peptide cleavage and N-linked glycosylation. 25486605 3 64 theme translocation 615:627 arg1 system 629:634 the translocation system 611:634 the translocation system 611:634 We isolated Sf21 microsomes from cultured insect cells by a simplified isolation procedure and evaluated the performance of the translocation system in combination with a cell-free translation system originating from the same source. 25486605 5 65 theme transporter 1003:1013 arg1 protein 1015:1021 A transporter protein 1001:1021 A transporter protein synthesized with the cell-free system 1001:1059 A transporter protein synthesized with the cell-free system could be functionally reconstituted into a lipid bilayer. 25486605 8 66 theme proteins 1675:1682 arg1 biogenesis 1592:1601 the biogenesis 1588:1601 the biogenesis of properly folded polytopic membrane proteins as well as tail-anchored proteins 1588:1682 These results showed that the newly developed cell-free translocation system derived from cultured insect cells is a practical tool for the biogenesis of properly folded polytopic membrane proteins as well as tail-anchored proteins. 25486605 4 67 theme signal 949:954 arg1 cleavage 964:971 signal peptide cleavage 949:971 signal peptide cleavage 949:971 The isolated microsomes contained the basic translocation machinery for polytopic membrane proteins including SRP-dependent targeting components, translocation channel (translocon)-dependent translocation, and the apparatus for signal peptide cleavage and N-linked glycosylation. 25486605 1 68 dep targeting 239:247 arg1 the 235:237 the 235:237 the 235:237 Cell-free protein synthesis is a powerful method to explore the structure and function of membrane proteins and to analyze the targeting and translocation of proteins across the ER membrane. 25486605 3 69 theme system 629:634 arg1 performance 596:606 the performance 592:606 the performance of the translocation system 592:634 We isolated Sf21 microsomes from cultured insect cells by a simplified isolation procedure and evaluated the performance of the translocation system in combination with a cell-free translation system originating from the same source. 25486605 4 70 theme basic 759:763 arg1 machinery 779:787 the basic translocation machinery 755:787 the basic translocation machinery for polytopic membrane proteins including SRP-dependent targeting components, translocation channel (translocon)-dependent translocation, and the apparatus for signal peptide cleavage and N-linked glycosylation 755:998 The isolated microsomes contained the basic translocation machinery for polytopic membrane proteins including SRP-dependent targeting components, translocation channel (translocon)-dependent translocation, and the apparatus for signal peptide cleavage and N-linked glycosylation. 25486605 2 71 theme cell-free 316:324 arg1 system 326:331 a cell-free system 314:331 a cell-free system based on cultured cells for the synthesis of membrane proteins 314:394 Developing a cell-free system based on cultured cells for the synthesis of membrane proteins could provide a highly reproducible alternative to the use of tissues from living animals. 25486605 8 72 theme tail-anchored 1661:1673 arg1 proteins 1675:1682 tail-anchored proteins 1661:1682 properly folded polytopic membrane proteins as well as tail-anchored proteins 1606:1682 These results showed that the newly developed cell-free translocation system derived from cultured insect cells is a practical tool for the biogenesis of properly folded polytopic membrane proteins as well as tail-anchored proteins. 25486605 0 73 theme cells 67:71 arg1 extracts 39:46 extracts 39:46 extracts of cultured insect cells 39:71 A cell-free translocation system using extracts of cultured insect cells to yield functional membrane proteins. 25486605 3 74 theme translation 668:678 arg1 system 680:685 a cell-free translation system 656:685 a cell-free translation system originating from the same source 656:718 We isolated Sf21 microsomes from cultured insect cells by a simplified isolation procedure and evaluated the performance of the translocation system in combination with a cell-free translation system originating from the same source. 25486605 4 75 theme targeting 845:853 arg1 components 855:864 SRP-dependent targeting components 831:864 SRP-dependent targeting components 831:864 The isolated microsomes contained the basic translocation machinery for polytopic membrane proteins including SRP-dependent targeting components, translocation channel (translocon)-dependent translocation, and the apparatus for signal peptide cleavage and N-linked glycosylation. 25486605 6 76 theme amino 1176:1180 arg1 acids 1182:1186 non-natural amino acids 1164:1186 non-natural amino acids 1164:1186 In addition, single and double labeling with non-natural amino acids could be achieved at both the lumen side and the cytosolic side in this system. 25486605 4 77 dep -dependent 901:910 arg1 channel 881:887 translocation channel 867:887 translocation channel 867:887 The isolated microsomes contained the basic translocation machinery for polytopic membrane proteins including SRP-dependent targeting components, translocation channel (translocon)-dependent translocation, and the apparatus for signal peptide cleavage and N-linked glycosylation. 25486605 0 78 theme insect 60:65 arg1 cells 67:71 cultured insect cells 51:71 cultured insect cells 51:71 A cell-free translocation system using extracts of cultured insect cells to yield functional membrane proteins. 25486605 3 79 theme same 708:711 arg1 source 713:718 the same source 704:718 the same source 704:718 We isolated Sf21 microsomes from cultured insect cells by a simplified isolation procedure and evaluated the performance of the translocation system in combination with a cell-free translation system originating from the same source. 25486605 0 80 theme translocation 12:24 arg1 system 26:31 A cell-free translocation system 0:31 A cell-free translocation system using extracts of cultured insect cells 0:71 A cell-free translocation system using extracts of cultured insect cells to yield functional membrane proteins. 25486605 1 81 theme powerful 145:152 arg1 synthesis 130:138 Cell-free protein synthesis 112:138 Cell-free protein synthesis 112:138 Cell-free protein synthesis is a powerful method to explore the structure and function of membrane proteins and to analyze the targeting and translocation of proteins across the ER membrane. 25486605 1 81 theme powerful 145:152 arg1 method 154:159 a powerful method 143:159 a powerful method to explore the structure and function of membrane proteins and to analyze the targeting and translocation of proteins across the ER membrane 143:300 Cell-free protein synthesis is a powerful method to explore the structure and function of membrane proteins and to analyze the targeting and translocation of proteins across the ER membrane. 24435307 5 0 from Loss 579:582 arg1 lines 642:646 DU145 and PC3 prostate cancer cell lines 607:646 lines 642:646 Loss of TUSC3 expression in DU145 and PC3 prostate cancer cell lines leads to increased proliferation, migration and invasion as well as accelerated xenograft growth in a PTEN negative background. 24435307 7 1 from general 1015:1021 arg1 particular 1046:1055 particular 1046:1055 particular 1046:1055 Together, our findings provide first mechanistic insight in TUSC3 function in prostate carcinogenesis in general and N-glycosylation in particular. 24435307 0 2 theme cancer 66:71 arg1 growth 73:78 prostate cancer growth 57:78 prostate cancer growth 57:78 TUSC3 loss alters the ER stress response and accelerates prostate cancer growth in vivo. 24435307 5 3 theme xenograft 728:736 arg1 growth 738:743 accelerated xenograft growth 716:743 accelerated xenograft growth in a PTEN negative background 716:773 Loss of TUSC3 expression in DU145 and PC3 prostate cancer cell lines leads to increased proliferation, migration and invasion as well as accelerated xenograft growth in a PTEN negative background. 24435307 5 4 theme DU145 607:611 arg1 lines 642:646 DU145 and PC3 prostate cancer cell lines 607:646 lines 642:646 Loss of TUSC3 expression in DU145 and PC3 prostate cancer cell lines leads to increased proliferation, migration and invasion as well as accelerated xenograft growth in a PTEN negative background. 24435307 6 5 theme endoplasmic 810:820 arg1 reticulum 822:830 endoplasmic reticulum 810:830 endoplasmic reticulum (ER) structure 810:845 TUSC3 downregulation also affects endoplasmic reticulum (ER) structure and stress response, which results in increased Akt signaling. 24435307 6 5 theme endoplasmic 810:820 arg1 ER 833:834 ER 833:834 ER 833:834 TUSC3 downregulation also affects endoplasmic reticulum (ER) structure and stress response, which results in increased Akt signaling. 24435307 5 6 from proliferation 667:679 arg1 background 764:773 a PTEN negative background 748:773 a PTEN negative background 748:773 Loss of TUSC3 expression in DU145 and PC3 prostate cancer cell lines leads to increased proliferation, migration and invasion as well as accelerated xenograft growth in a PTEN negative background. 24435307 4 7 from glycosylation 545:557 arg1 cells 572:576 mammalian cells 562:576 mammalian cells 562:576 We provide evidence that TUSC3 is part of the OST complex and affects N-linked glycosylation in mammalian cells. 24435307 5 8 from growth 738:743 arg1 background 764:773 a PTEN negative background 748:773 a PTEN negative background 748:773 Loss of TUSC3 expression in DU145 and PC3 prostate cancer cell lines leads to increased proliferation, migration and invasion as well as accelerated xenograft growth in a PTEN negative background. 24435307 6 9 theme stress 851:856 arg1 response 858:865 stress response 851:865 stress response 851:865 TUSC3 downregulation also affects endoplasmic reticulum (ER) structure and stress response, which results in increased Akt signaling. 24435307 5 10 theme PC3 617:619 arg1 lines 642:646 DU145 and PC3 prostate cancer cell lines 607:646 lines 642:646 Loss of TUSC3 expression in DU145 and PC3 prostate cancer cell lines leads to increased proliferation, migration and invasion as well as accelerated xenograft growth in a PTEN negative background. 24435307 2 11 theme suppressor 244:253 arg1 gene 255:258 a putative tumor suppressor gene 227:258 a putative tumor suppressor gene in prostate cancer 227:277 Tumor suppressor candidate 3 (TUSC3) has been identified as a putative tumor suppressor gene in prostate cancer, though its function has not been characterized. 24435307 2 11 theme suppressor 244:253 arg1 candidate 184:192 Tumor suppressor candidate 3 167:194 Tumor suppressor candidate 3 (TUSC3) 167:202 Tumor suppressor candidate 3 (TUSC3) has been identified as a putative tumor suppressor gene in prostate cancer, though its function has not been characterized. 24435307 4 12 theme N-linked 536:543 arg1 glycosylation 545:557 N-linked glycosylation 536:557 N-linked glycosylation in mammalian cells 536:576 We provide evidence that TUSC3 is part of the OST complex and affects N-linked glycosylation in mammalian cells. 24435307 1 13 from cancer 127:132 arg1 countries 156:164 developed countries 146:164 developed countries 146:164 Prostate cancer is the most prevalent cancer in males in developed countries. 24435307 1 13 from cancer 127:132 arg1 males 137:141 males 137:141 males 137:141 Prostate cancer is the most prevalent cancer in males in developed countries. 24435307 2 14 theme tumor 238:242 arg1 gene 255:258 a putative tumor suppressor gene 227:258 a putative tumor suppressor gene in prostate cancer 227:277 Tumor suppressor candidate 3 (TUSC3) has been identified as a putative tumor suppressor gene in prostate cancer, though its function has not been characterized. 24435307 2 14 theme tumor 238:242 arg1 candidate 184:192 Tumor suppressor candidate 3 167:194 Tumor suppressor candidate 3 (TUSC3) 167:202 Tumor suppressor candidate 3 (TUSC3) has been identified as a putative tumor suppressor gene in prostate cancer, though its function has not been characterized. 24435307 3 15 theme complex 399:405 arg1 subunit 407:413 the yeast oligosaccharyltransferase (OST) complex subunit 357:413 the yeast oligosaccharyltransferase (OST) complex subunit Ost3p 357:419 TUSC3 shares homologies with the yeast oligosaccharyltransferase (OST) complex subunit Ost3p, suggesting a role in protein glycosylation. 24435307 3 15 theme complex 399:405 arg1 Ost3p 415:419 Ost3p 415:419 Ost3p 415:419 TUSC3 shares homologies with the yeast oligosaccharyltransferase (OST) complex subunit Ost3p, suggesting a role in protein glycosylation. 24435307 0 16 theme stress 25:30 arg1 response 32:39 the ER stress response 18:39 the ER stress response 18:39 TUSC3 loss alters the ER stress response and accelerates prostate cancer growth in vivo. 24435307 3 17 from role 435:438 arg1 glycosylation 451:463 protein glycosylation 443:463 protein glycosylation 443:463 TUSC3 shares homologies with the yeast oligosaccharyltransferase (OST) complex subunit Ost3p, suggesting a role in protein glycosylation. 24435307 2 18 theme putative 229:236 arg1 gene 255:258 a putative tumor suppressor gene 227:258 a putative tumor suppressor gene in prostate cancer 227:277 Tumor suppressor candidate 3 (TUSC3) has been identified as a putative tumor suppressor gene in prostate cancer, though its function has not been characterized. 24435307 2 18 theme putative 229:236 arg1 candidate 184:192 Tumor suppressor candidate 3 167:194 Tumor suppressor candidate 3 (TUSC3) 167:202 Tumor suppressor candidate 3 (TUSC3) has been identified as a putative tumor suppressor gene in prostate cancer, though its function has not been characterized. 24435307 1 19 theme developed 146:154 arg1 countries 156:164 developed countries 146:164 developed countries 146:164 Prostate cancer is the most prevalent cancer in males in developed countries. 24435307 5 20 theme PTEN 750:753 arg1 background 764:773 a PTEN negative background 748:773 a PTEN negative background 748:773 Loss of TUSC3 expression in DU145 and PC3 prostate cancer cell lines leads to increased proliferation, migration and invasion as well as accelerated xenograft growth in a PTEN negative background. 24435307 5 21 theme accelerated 716:726 arg1 growth 738:743 accelerated xenograft growth 716:743 accelerated xenograft growth in a PTEN negative background 716:773 Loss of TUSC3 expression in DU145 and PC3 prostate cancer cell lines leads to increased proliferation, migration and invasion as well as accelerated xenograft growth in a PTEN negative background. 24435307 5 22 theme TUSC3 587:591 arg1 expression 593:602 TUSC3 expression 587:602 TUSC3 expression in DU145 and PC3 prostate cancer cell lines 587:646 Loss of TUSC3 expression in DU145 and PC3 prostate cancer cell lines leads to increased proliferation, migration and invasion as well as accelerated xenograft growth in a PTEN negative background. 24435307 0 23 theme TUSC3 0:4 arg1 loss 6:9 TUSC3 loss 0:9 TUSC3 loss 0:9 TUSC3 loss alters the ER stress response and accelerates prostate cancer growth in vivo. 24435307 7 24 from particular 1046:1055 arg1 general 1015:1021 general 1015:1021 general 1015:1021 Together, our findings provide first mechanistic insight in TUSC3 function in prostate carcinogenesis in general and N-glycosylation in particular. 24435307 5 25 theme expression 593:602 arg1 Loss 579:582 Loss 579:582 Loss of TUSC3 expression in DU145 and PC3 prostate cancer cell lines 579:646 Loss of TUSC3 expression in DU145 and PC3 prostate cancer cell lines leads to increased proliferation, migration and invasion as well as accelerated xenograft growth in a PTEN negative background. 24435307 5 26 theme negative 755:762 arg1 background 764:773 a PTEN negative background 748:773 a PTEN negative background 748:773 Loss of TUSC3 expression in DU145 and PC3 prostate cancer cell lines leads to increased proliferation, migration and invasion as well as accelerated xenograft growth in a PTEN negative background. 24435307 4 27 gly glycosylation 545:557 arg1 cells 572:576 mammalian cells 562:576 mammalian cells 562:576 We provide evidence that TUSC3 is part of the OST complex and affects N-linked glycosylation in mammalian cells. 24435307 2 28 theme prostate 263:270 arg1 cancer 272:277 prostate cancer 263:277 prostate cancer 263:277 Tumor suppressor candidate 3 (TUSC3) has been identified as a putative tumor suppressor gene in prostate cancer, though its function has not been characterized. 24435307 7 29 from insight 959:965 arg1 function 976:983 TUSC3 function 970:983 TUSC3 function in prostate carcinogenesis in general and N-glycosylation in particular 970:1055 Together, our findings provide first mechanistic insight in TUSC3 function in prostate carcinogenesis in general and N-glycosylation in particular. 24435307 4 30 theme complex 516:522 arg1 part 500:503 part 500:503 part of the OST complex 500:522 We provide evidence that TUSC3 is part of the OST complex and affects N-linked glycosylation in mammalian cells. 24435307 1 31 theme Prostate 89:96 arg1 cancer 127:132 the most prevalent cancer 108:132 the most prevalent cancer in males in developed countries 108:164 Prostate cancer is the most prevalent cancer in males in developed countries. 24435307 1 31 theme Prostate 89:96 arg1 cancer 98:103 Prostate cancer 89:103 Prostate cancer 89:103 Prostate cancer is the most prevalent cancer in males in developed countries. 24435307 3 32 theme oligosaccharyltransferase 367:391 arg1 subunit 407:413 the yeast oligosaccharyltransferase (OST) complex subunit 357:413 the yeast oligosaccharyltransferase (OST) complex subunit Ost3p 357:419 TUSC3 shares homologies with the yeast oligosaccharyltransferase (OST) complex subunit Ost3p, suggesting a role in protein glycosylation. 24435307 3 32 theme oligosaccharyltransferase 367:391 arg1 Ost3p 415:419 Ost3p 415:419 Ost3p 415:419 TUSC3 shares homologies with the yeast oligosaccharyltransferase (OST) complex subunit Ost3p, suggesting a role in protein glycosylation. 24435307 4 33 theme OST 512:514 arg1 complex 516:522 the OST complex 508:522 the OST complex 508:522 We provide evidence that TUSC3 is part of the OST complex and affects N-linked glycosylation in mammalian cells. 24435307 5 34 theme increased 657:665 arg1 proliferation 667:679 increased proliferation 657:679 increased proliferation 657:679 Loss of TUSC3 expression in DU145 and PC3 prostate cancer cell lines leads to increased proliferation, migration and invasion as well as accelerated xenograft growth in a PTEN negative background. 24435307 5 35 from invasion 696:703 arg1 background 764:773 a PTEN negative background 748:773 a PTEN negative background 748:773 Loss of TUSC3 expression in DU145 and PC3 prostate cancer cell lines leads to increased proliferation, migration and invasion as well as accelerated xenograft growth in a PTEN negative background. 24435307 0 36 theme ER 22:23 arg1 response 32:39 the ER stress response 18:39 the ER stress response 18:39 TUSC3 loss alters the ER stress response and accelerates prostate cancer growth in vivo. 24435307 6 37 theme reticulum 822:830 arg1 structure 837:845 endoplasmic reticulum (ER) structure 810:845 endoplasmic reticulum (ER) structure 810:845 TUSC3 downregulation also affects endoplasmic reticulum (ER) structure and stress response, which results in increased Akt signaling. 24435307 7 38 from carcinogenesis 997:1010 arg1 N-glycosylation 1027:1041 N-glycosylation 1027:1041 N-glycosylation 1027:1041 Together, our findings provide first mechanistic insight in TUSC3 function in prostate carcinogenesis in general and N-glycosylation in particular. 24435307 7 38 from carcinogenesis 997:1010 arg1 general 1015:1021 general 1015:1021 general 1015:1021 Together, our findings provide first mechanistic insight in TUSC3 function in prostate carcinogenesis in general and N-glycosylation in particular. 24435307 7 39 theme TUSC3 970:974 arg1 function 976:983 TUSC3 function 970:983 TUSC3 function in prostate carcinogenesis in general and N-glycosylation in particular 970:1055 Together, our findings provide first mechanistic insight in TUSC3 function in prostate carcinogenesis in general and N-glycosylation in particular. 24435307 7 40 from function 976:983 arg1 carcinogenesis 997:1010 prostate carcinogenesis 988:1010 prostate carcinogenesis in general and N-glycosylation in particular 988:1055 Together, our findings provide first mechanistic insight in TUSC3 function in prostate carcinogenesis in general and N-glycosylation in particular. 24435307 6 41 theme Akt 895:897 arg1 signaling 899:907 increased Akt signaling 885:907 increased Akt signaling 885:907 TUSC3 downregulation also affects endoplasmic reticulum (ER) structure and stress response, which results in increased Akt signaling. 24435307 5 42 theme prostate 621:628 arg1 lines 642:646 DU145 and PC3 prostate cancer cell lines 607:646 lines 642:646 Loss of TUSC3 expression in DU145 and PC3 prostate cancer cell lines leads to increased proliferation, migration and invasion as well as accelerated xenograft growth in a PTEN negative background. 24435307 5 43 from migration 682:690 arg1 background 764:773 a PTEN negative background 748:773 a PTEN negative background 748:773 Loss of TUSC3 expression in DU145 and PC3 prostate cancer cell lines leads to increased proliferation, migration and invasion as well as accelerated xenograft growth in a PTEN negative background. 24435307 3 44 theme protein 443:449 arg1 glycosylation 451:463 protein glycosylation 443:463 protein glycosylation 443:463 TUSC3 shares homologies with the yeast oligosaccharyltransferase (OST) complex subunit Ost3p, suggesting a role in protein glycosylation. 24435307 3 45 theme yeast 361:365 arg1 OST 394:396 OST 394:396 OST 394:396 TUSC3 shares homologies with the yeast oligosaccharyltransferase (OST) complex subunit Ost3p, suggesting a role in protein glycosylation. 24435307 3 45 theme yeast 361:365 arg1 oligosaccharyltransferase 367:391 yeast oligosaccharyltransferase 361:391 the yeast oligosaccharyltransferase (OST) complex subunit Ost3p 357:419 TUSC3 shares homologies with the yeast oligosaccharyltransferase (OST) complex subunit Ost3p, suggesting a role in protein glycosylation. 24435307 6 46 theme increased 885:893 arg1 signaling 899:907 increased Akt signaling 885:907 increased Akt signaling 885:907 TUSC3 downregulation also affects endoplasmic reticulum (ER) structure and stress response, which results in increased Akt signaling. 24435307 5 47 theme cancer 630:635 arg1 lines 642:646 DU145 and PC3 prostate cancer cell lines 607:646 lines 642:646 Loss of TUSC3 expression in DU145 and PC3 prostate cancer cell lines leads to increased proliferation, migration and invasion as well as accelerated xenograft growth in a PTEN negative background. 24435307 5 48 theme cell 637:640 arg1 lines 642:646 DU145 and PC3 prostate cancer cell lines 607:646 lines 642:646 Loss of TUSC3 expression in DU145 and PC3 prostate cancer cell lines leads to increased proliferation, migration and invasion as well as accelerated xenograft growth in a PTEN negative background. 24435307 4 49 link N-linked 536:543 arg1 glycosylation 545:557 N-linked glycosylation 536:557 N-linked glycosylation in mammalian cells 536:576 We provide evidence that TUSC3 is part of the OST complex and affects N-linked glycosylation in mammalian cells. 24435307 5 50 from expression 593:602 arg1 lines 642:646 DU145 and PC3 prostate cancer cell lines 607:646 lines 642:646 Loss of TUSC3 expression in DU145 and PC3 prostate cancer cell lines leads to increased proliferation, migration and invasion as well as accelerated xenograft growth in a PTEN negative background. 24435307 4 51 theme mammalian 562:570 arg1 cells 572:576 mammalian cells 562:576 mammalian cells 562:576 We provide evidence that TUSC3 is part of the OST complex and affects N-linked glycosylation in mammalian cells. 24435307 7 52 theme prostate 988:995 arg1 carcinogenesis 997:1010 prostate carcinogenesis 988:1010 prostate carcinogenesis in general and N-glycosylation in particular 988:1055 Together, our findings provide first mechanistic insight in TUSC3 function in prostate carcinogenesis in general and N-glycosylation in particular. 24435307 2 53 theme suppressor 173:182 arg1 gene 255:258 a putative tumor suppressor gene 227:258 a putative tumor suppressor gene in prostate cancer 227:277 Tumor suppressor candidate 3 (TUSC3) has been identified as a putative tumor suppressor gene in prostate cancer, though its function has not been characterized. 24435307 2 53 theme suppressor 173:182 arg1 candidate 184:192 Tumor suppressor candidate 3 167:194 Tumor suppressor candidate 3 (TUSC3) 167:202 Tumor suppressor candidate 3 (TUSC3) has been identified as a putative tumor suppressor gene in prostate cancer, though its function has not been characterized. 24435307 2 53 theme suppressor 173:182 arg1 TUSC3 197:201 TUSC3 197:201 TUSC3 197:201 Tumor suppressor candidate 3 (TUSC3) has been identified as a putative tumor suppressor gene in prostate cancer, though its function has not been characterized. 24435307 7 54 theme first 941:945 arg1 insight 959:965 first mechanistic insight 941:965 first mechanistic insight in TUSC3 function in prostate carcinogenesis in general and N-glycosylation in particular 941:1055 Together, our findings provide first mechanistic insight in TUSC3 function in prostate carcinogenesis in general and N-glycosylation in particular. 24435307 2 55 from gene 255:258 arg1 cancer 272:277 prostate cancer 263:277 prostate cancer 263:277 Tumor suppressor candidate 3 (TUSC3) has been identified as a putative tumor suppressor gene in prostate cancer, though its function has not been characterized. 24435307 5 56 from lines 642:646 arg1 Loss 579:582 Loss 579:582 Loss of TUSC3 expression in DU145 and PC3 prostate cancer cell lines 579:646 Loss of TUSC3 expression in DU145 and PC3 prostate cancer cell lines leads to increased proliferation, migration and invasion as well as accelerated xenograft growth in a PTEN negative background. 24435307 0 57 theme prostate 57:64 arg1 growth 73:78 prostate cancer growth 57:78 prostate cancer growth 57:78 TUSC3 loss alters the ER stress response and accelerates prostate cancer growth in vivo. 24435307 2 58 theme Tumor 167:171 arg1 gene 255:258 a putative tumor suppressor gene 227:258 a putative tumor suppressor gene in prostate cancer 227:277 Tumor suppressor candidate 3 (TUSC3) has been identified as a putative tumor suppressor gene in prostate cancer, though its function has not been characterized. 24435307 2 58 theme Tumor 167:171 arg1 candidate 184:192 Tumor suppressor candidate 3 167:194 Tumor suppressor candidate 3 (TUSC3) 167:202 Tumor suppressor candidate 3 (TUSC3) has been identified as a putative tumor suppressor gene in prostate cancer, though its function has not been characterized. 24435307 2 58 theme Tumor 167:171 arg1 TUSC3 197:201 TUSC3 197:201 TUSC3 197:201 Tumor suppressor candidate 3 (TUSC3) has been identified as a putative tumor suppressor gene in prostate cancer, though its function has not been characterized. 24435307 7 59 theme mechanistic 947:957 arg1 insight 959:965 first mechanistic insight 941:965 first mechanistic insight in TUSC3 function in prostate carcinogenesis in general and N-glycosylation in particular 941:1055 Together, our findings provide first mechanistic insight in TUSC3 function in prostate carcinogenesis in general and N-glycosylation in particular. 24435307 1 60 theme prevalent 117:125 arg1 cancer 127:132 the most prevalent cancer 108:132 the most prevalent cancer in males in developed countries 108:164 Prostate cancer is the most prevalent cancer in males in developed countries. 24435307 1 60 theme prevalent 117:125 arg1 cancer 98:103 Prostate cancer 89:103 Prostate cancer 89:103 Prostate cancer is the most prevalent cancer in males in developed countries. 24435307 6 61 theme TUSC3 776:780 arg1 downregulation 782:795 TUSC3 downregulation 776:795 TUSC3 downregulation 776:795 TUSC3 downregulation also affects endoplasmic reticulum (ER) structure and stress response, which results in increased Akt signaling. 28630348 4 0 with structure 723:731 arg1 architecture 750:761 dual domain architecture 738:761 dual domain architecture featuring a C-terminal soluble globular domain and a predicted N-terminal membrane-associated domain 738:862 In contrast, less is known about a second, extensive superfamily of PGTs that reveals a core structure with dual domain architecture featuring a C-terminal soluble globular domain and a predicted N-terminal membrane-associated domain. 28630348 2 1 theme PGT 387:389 arg1 superfamilies 391:403 two PGT superfamilies 383:403 two PGT superfamilies that differ significantly in overall structure and topology 383:463 There are two PGT superfamilies that differ significantly in overall structure and topology. 28630348 9 2 theme covalent 1722:1729 arg1 intermediate 1744:1755 a covalent phosphosugar intermediate 1720:1755 a covalent phosphosugar intermediate 1720:1755 The existence of a covalent phosphosugar intermediate provides strong support for a ping-pong mechanism of PglC, differing fundamentally from the ternary complex mechanisms of representative polytopic PGTs. 28630348 7 3 theme PglC 1165:1168 arg1 analysis 1153:1160 the mechanistic analysis 1137:1160 the mechanistic analysis of PglC, a prototypic dual domain PGT from Campylobacter concisus 1137:1226 Here, we present the mechanistic analysis of PglC, a prototypic dual domain PGT from Campylobacter concisus Using a luminescence-based assay, together with substrate labeling and kinetics-based approaches, complementary experiments were carried out that support a ping-pong mechanism involving a covalent phosphosugar intermediate for PglC. 28630348 9 4 theme intermediate 1744:1755 arg1 existence 1707:1715 The existence 1703:1715 The existence of a covalent phosphosugar intermediate 1703:1755 The existence of a covalent phosphosugar intermediate provides strong support for a ping-pong mechanism of PglC, differing fundamentally from the ternary complex mechanisms of representative polytopic PGTs. 28630348 1 5 from diphosphate-sugar 328:344 arg1 transfer 301:308 phosphosugar transfer 288:308 phosphosugar transfer from a nucleotide diphosphate-sugar to a polyprenol phosphate 288:370 Phosphoglycosyl transferases (PGTs) are integral membrane proteins with diverse architectures that catalyze the formation of polyprenol diphosphate-linked glycans via phosphosugar transfer from a nucleotide diphosphate-sugar to a polyprenol phosphate. 28630348 9 6 theme strong 1766:1771 arg1 support 1773:1779 strong support 1766:1779 strong support for a ping-pong mechanism of PglC, differing fundamentally from the ternary complex mechanisms of representative polytopic PGTs 1766:1907 The existence of a covalent phosphosugar intermediate provides strong support for a ping-pong mechanism of PglC, differing fundamentally from the ternary complex mechanisms of representative polytopic PGTs. 28630348 1 7 theme diverse 193:199 arg1 architectures 201:213 diverse architectures 193:213 diverse architectures 193:213 Phosphoglycosyl transferases (PGTs) are integral membrane proteins with diverse architectures that catalyze the formation of polyprenol diphosphate-linked glycans via phosphosugar transfer from a nucleotide diphosphate-sugar to a polyprenol phosphate. 28630348 9 8 theme ping-pong 1787:1795 arg1 mechanism 1797:1805 a ping-pong mechanism 1785:1805 a ping-pong mechanism of PglC, differing fundamentally from the ternary complex mechanisms of representative polytopic PGTs 1785:1907 The existence of a covalent phosphosugar intermediate provides strong support for a ping-pong mechanism of PglC, differing fundamentally from the ternary complex mechanisms of representative polytopic PGTs. 28630348 4 9 theme second 665:670 arg1 superfamily 683:693 a second, extensive superfamily 663:693 a second, extensive superfamily of PGTs that reveals a core structure with dual domain architecture featuring a C-terminal soluble globular domain and a predicted N-terminal membrane-associated domain 663:862 In contrast, less is known about a second, extensive superfamily of PGTs that reveals a core structure with dual domain architecture featuring a C-terminal soluble globular domain and a predicted N-terminal membrane-associated domain. 28630348 5 10 theme superfamily 896:906 arg1 members 880:886 Representative members 865:886 Representative members of this superfamily 865:906 Representative members of this superfamily are the Campylobacter PglCs, which initiate N-linked glycoprotein biosynthesis and are implicated in virulence and pathogenicity. 28630348 5 10 theme superfamily 896:906 arg1 PglCs 930:934 the Campylobacter PglCs 912:934 the Campylobacter PglCs 912:934 Representative members of this superfamily are the Campylobacter PglCs, which initiate N-linked glycoprotein biosynthesis and are implicated in virulence and pathogenicity. 28630348 1 11 theme Phosphoglycosyl 121:135 arg1 transferases 137:148 Phosphoglycosyl transferases 121:148 Phosphoglycosyl transferases (PGTs) 121:155 Phosphoglycosyl transferases (PGTs) are integral membrane proteins with diverse architectures that catalyze the formation of polyprenol diphosphate-linked glycans via phosphosugar transfer from a nucleotide diphosphate-sugar to a polyprenol phosphate. 28630348 1 11 theme Phosphoglycosyl 121:135 arg1 proteins 179:186 integral membrane proteins 161:186 integral membrane proteins with diverse architectures that catalyze the formation of polyprenol diphosphate-linked glycans via phosphosugar transfer from a nucleotide diphosphate-sugar to a polyprenol phosphate 161:370 Phosphoglycosyl transferases (PGTs) are integral membrane proteins with diverse architectures that catalyze the formation of polyprenol diphosphate-linked glycans via phosphosugar transfer from a nucleotide diphosphate-sugar to a polyprenol phosphate. 28630348 1 11 theme Phosphoglycosyl 121:135 arg1 PGTs 151:154 PGTs 151:154 PGTs 151:154 Phosphoglycosyl transferases (PGTs) are integral membrane proteins with diverse architectures that catalyze the formation of polyprenol diphosphate-linked glycans via phosphosugar transfer from a nucleotide diphosphate-sugar to a polyprenol phosphate. 28630348 8 12 theme conserved 1555:1563 arg1 dyad 1572:1575 a highly conserved AspGlu dyad 1546:1575 a highly conserved AspGlu dyad found in all dual domain PGTs 1546:1605 Significantly, mass spectrometry-based approaches identified Asp93, which is part of a highly conserved AspGlu dyad found in all dual domain PGTs, as the active-site nucleophile of the enzyme involved in the formation of the covalent adduct. 28630348 4 13 theme dual 738:741 arg1 architecture 750:761 dual domain architecture 738:761 dual domain architecture featuring a C-terminal soluble globular domain and a predicted N-terminal membrane-associated domain 738:862 In contrast, less is known about a second, extensive superfamily of PGTs that reveals a core structure with dual domain architecture featuring a C-terminal soluble globular domain and a predicted N-terminal membrane-associated domain. 28630348 8 14 theme dyad 1572:1575 arg1 part 1538:1541 part 1538:1541 part of a highly conserved AspGlu dyad found in all dual domain PGTs 1538:1605 Significantly, mass spectrometry-based approaches identified Asp93, which is part of a highly conserved AspGlu dyad found in all dual domain PGTs, as the active-site nucleophile of the enzyme involved in the formation of the covalent adduct. 28630348 7 15 theme covalent 1416:1423 arg1 intermediate 1438:1449 a covalent phosphosugar intermediate 1414:1449 a covalent phosphosugar intermediate for PglC 1414:1458 Here, we present the mechanistic analysis of PglC, a prototypic dual domain PGT from Campylobacter concisus Using a luminescence-based assay, together with substrate labeling and kinetics-based approaches, complementary experiments were carried out that support a ping-pong mechanism involving a covalent phosphosugar intermediate for PglC. 28630348 6 16 theme PGTs 1076:1079 arg1 prevalence 1050:1059 the prevalence 1046:1059 the prevalence of dual domain PGTs 1046:1079 Despite the prevalence of dual domain PGTs, their mechanism of action is unknown. 28630348 1 17 theme integral 161:168 arg1 transferases 137:148 Phosphoglycosyl transferases 121:148 Phosphoglycosyl transferases (PGTs) 121:155 Phosphoglycosyl transferases (PGTs) are integral membrane proteins with diverse architectures that catalyze the formation of polyprenol diphosphate-linked glycans via phosphosugar transfer from a nucleotide diphosphate-sugar to a polyprenol phosphate. 28630348 1 17 theme integral 161:168 arg1 proteins 179:186 integral membrane proteins 161:186 integral membrane proteins with diverse architectures that catalyze the formation of polyprenol diphosphate-linked glycans via phosphosugar transfer from a nucleotide diphosphate-sugar to a polyprenol phosphate 161:370 Phosphoglycosyl transferases (PGTs) are integral membrane proteins with diverse architectures that catalyze the formation of polyprenol diphosphate-linked glycans via phosphosugar transfer from a nucleotide diphosphate-sugar to a polyprenol phosphate. 28630348 6 18 theme dual 1064:1067 arg1 PGTs 1076:1079 dual domain PGTs 1064:1079 dual domain PGTs 1064:1079 Despite the prevalence of dual domain PGTs, their mechanism of action is unknown. 28630348 9 19 theme complex 1857:1863 arg1 mechanisms 1865:1874 the ternary complex mechanisms 1845:1874 the ternary complex mechanisms of representative polytopic PGTs 1845:1907 The existence of a covalent phosphosugar intermediate provides strong support for a ping-pong mechanism of PglC, differing fundamentally from the ternary complex mechanisms of representative polytopic PGTs. 28630348 8 20 theme dual 1590:1593 arg1 PGTs 1602:1605 all dual domain PGTs 1586:1605 all dual domain PGTs 1586:1605 Significantly, mass spectrometry-based approaches identified Asp93, which is part of a highly conserved AspGlu dyad found in all dual domain PGTs, as the active-site nucleophile of the enzyme involved in the formation of the covalent adduct. 28630348 4 21 theme soluble 786:792 arg1 domain 803:808 a C-terminal soluble globular domain 773:808 a C-terminal soluble globular domain 773:808 In contrast, less is known about a second, extensive superfamily of PGTs that reveals a core structure with dual domain architecture featuring a C-terminal soluble globular domain and a predicted N-terminal membrane-associated domain. 28630348 7 22 from Campylobacter 1205:1217 arg1 PglC 1165:1168 PglC 1165:1168 PglC 1165:1168 Here, we present the mechanistic analysis of PglC, a prototypic dual domain PGT from Campylobacter concisus Using a luminescence-based assay, together with substrate labeling and kinetics-based approaches, complementary experiments were carried out that support a ping-pong mechanism involving a covalent phosphosugar intermediate for PglC. 28630348 7 22 from Campylobacter 1205:1217 arg1 PGT 1196:1198 a prototypic dual domain PGT 1171:1198 a prototypic dual domain PGT from Campylobacter concisus 1171:1226 Here, we present the mechanistic analysis of PglC, a prototypic dual domain PGT from Campylobacter concisus Using a luminescence-based assay, together with substrate labeling and kinetics-based approaches, complementary experiments were carried out that support a ping-pong mechanism involving a covalent phosphosugar intermediate for PglC. 28630348 7 23 theme luminescence-based 1236:1253 arg1 assay 1255:1259 a luminescence-based assay 1234:1259 a luminescence-based assay 1234:1259 Here, we present the mechanistic analysis of PglC, a prototypic dual domain PGT from Campylobacter concisus Using a luminescence-based assay, together with substrate labeling and kinetics-based approaches, complementary experiments were carried out that support a ping-pong mechanism involving a covalent phosphosugar intermediate for PglC. 28630348 0 24 theme phosphoglycosyl 26:40 arg1 transferase 42:52 a dual domain phosphoglycosyl transferase 12:52 a dual domain phosphoglycosyl transferase 12:52 Analysis of a dual domain phosphoglycosyl transferase reveals a ping-pong mechanism with a covalent enzyme intermediate. 28630348 7 25 dep carried 1357:1363 arg1 out 1365:1367 out 1365:1367 out 1365:1367 Here, we present the mechanistic analysis of PglC, a prototypic dual domain PGT from Campylobacter concisus Using a luminescence-based assay, together with substrate labeling and kinetics-based approaches, complementary experiments were carried out that support a ping-pong mechanism involving a covalent phosphosugar intermediate for PglC. 28630348 9 26 theme polytopic 1894:1902 arg1 PGTs 1904:1907 representative polytopic PGTs 1879:1907 representative polytopic PGTs 1879:1907 The existence of a covalent phosphosugar intermediate provides strong support for a ping-pong mechanism of PglC, differing fundamentally from the ternary complex mechanisms of representative polytopic PGTs. 28630348 0 27 theme ping-pong 64:72 arg1 mechanism 74:82 a ping-pong mechanism 62:82 a ping-pong mechanism with a covalent enzyme intermediate 62:118 Analysis of a dual domain phosphoglycosyl transferase reveals a ping-pong mechanism with a covalent enzyme intermediate. 28630348 3 28 theme polytopic 470:478 arg1 superfamily 484:494 The polytopic PGT superfamily 466:494 The polytopic PGT superfamily 466:494 The polytopic PGT superfamily, represented by MraY and WecA, has been the subject of many studies because of its roles in peptidoglycan and O-antigen biosynthesis. 28630348 3 28 theme polytopic 470:478 arg1 subject 540:546 the subject 536:546 the subject of many studies 536:562 The polytopic PGT superfamily, represented by MraY and WecA, has been the subject of many studies because of its roles in peptidoglycan and O-antigen biosynthesis. 28630348 8 29 theme active-site 1615:1625 arg1 nucleophile 1627:1637 the active-site nucleophile 1611:1637 the active-site nucleophile of the enzyme involved in the formation of the covalent adduct 1611:1700 Significantly, mass spectrometry-based approaches identified Asp93, which is part of a highly conserved AspGlu dyad found in all dual domain PGTs, as the active-site nucleophile of the enzyme involved in the formation of the covalent adduct. 28630348 8 29 theme active-site 1615:1625 arg1 Asp93 1522:1526 Asp93 1522:1526 Asp93 1522:1526 Significantly, mass spectrometry-based approaches identified Asp93, which is part of a highly conserved AspGlu dyad found in all dual domain PGTs, as the active-site nucleophile of the enzyme involved in the formation of the covalent adduct. 28630348 5 30 theme Representative 865:878 arg1 members 880:886 Representative members 865:886 Representative members of this superfamily 865:906 Representative members of this superfamily are the Campylobacter PglCs, which initiate N-linked glycoprotein biosynthesis and are implicated in virulence and pathogenicity. 28630348 5 30 theme Representative 865:878 arg1 PglCs 930:934 the Campylobacter PglCs 912:934 the Campylobacter PglCs 912:934 Representative members of this superfamily are the Campylobacter PglCs, which initiate N-linked glycoprotein biosynthesis and are implicated in virulence and pathogenicity. 28630348 1 31 theme nucleotide 317:326 arg1 diphosphate-sugar 328:344 a nucleotide diphosphate-sugar 315:344 a nucleotide diphosphate-sugar 315:344 Phosphoglycosyl transferases (PGTs) are integral membrane proteins with diverse architectures that catalyze the formation of polyprenol diphosphate-linked glycans via phosphosugar transfer from a nucleotide diphosphate-sugar to a polyprenol phosphate. 28630348 5 32 link N-linked 952:959 arg1 biosynthesis 974:985 N-linked glycoprotein biosynthesis 952:985 N-linked glycoprotein biosynthesis 952:985 Representative members of this superfamily are the Campylobacter PglCs, which initiate N-linked glycoprotein biosynthesis and are implicated in virulence and pathogenicity. 28630348 8 33 theme spectrometry-based 1481:1498 arg1 approaches 1500:1509 mass spectrometry-based approaches 1476:1509 mass spectrometry-based approaches 1476:1509 Significantly, mass spectrometry-based approaches identified Asp93, which is part of a highly conserved AspGlu dyad found in all dual domain PGTs, as the active-site nucleophile of the enzyme involved in the formation of the covalent adduct. 28630348 0 34 theme domain 19:24 arg1 transferase 42:52 a dual domain phosphoglycosyl transferase 12:52 a dual domain phosphoglycosyl transferase 12:52 Analysis of a dual domain phosphoglycosyl transferase reveals a ping-pong mechanism with a covalent enzyme intermediate. 28630348 8 35 theme enzyme 1646:1651 arg1 nucleophile 1627:1637 the active-site nucleophile 1611:1637 the active-site nucleophile of the enzyme involved in the formation of the covalent adduct 1611:1700 Significantly, mass spectrometry-based approaches identified Asp93, which is part of a highly conserved AspGlu dyad found in all dual domain PGTs, as the active-site nucleophile of the enzyme involved in the formation of the covalent adduct. 28630348 8 35 theme enzyme 1646:1651 arg1 Asp93 1522:1526 Asp93 1522:1526 Asp93 1522:1526 Significantly, mass spectrometry-based approaches identified Asp93, which is part of a highly conserved AspGlu dyad found in all dual domain PGTs, as the active-site nucleophile of the enzyme involved in the formation of the covalent adduct. 28630348 0 36 theme transferase 42:52 arg1 Analysis 0:7 Analysis 0:7 Analysis of a dual domain phosphoglycosyl transferase 0:52 Analysis of a dual domain phosphoglycosyl transferase reveals a ping-pong mechanism with a covalent enzyme intermediate. 28630348 1 37 theme polyprenol 351:360 arg1 phosphate 362:370 a polyprenol phosphate 349:370 a polyprenol phosphate 349:370 Phosphoglycosyl transferases (PGTs) are integral membrane proteins with diverse architectures that catalyze the formation of polyprenol diphosphate-linked glycans via phosphosugar transfer from a nucleotide diphosphate-sugar to a polyprenol phosphate. 28630348 7 38 dep assay 1255:1259 arg1 carried 1357:1363 carried 1357:1363 were carried out that support a ping-pong mechanism involving a covalent phosphosugar intermediate for PglC 1352:1458 Here, we present the mechanistic analysis of PglC, a prototypic dual domain PGT from Campylobacter concisus Using a luminescence-based assay, together with substrate labeling and kinetics-based approaches, complementary experiments were carried out that support a ping-pong mechanism involving a covalent phosphosugar intermediate for PglC. 28630348 8 39 theme mass 1476:1479 arg1 approaches 1500:1509 mass spectrometry-based approaches 1476:1509 mass spectrometry-based approaches 1476:1509 Significantly, mass spectrometry-based approaches identified Asp93, which is part of a highly conserved AspGlu dyad found in all dual domain PGTs, as the active-site nucleophile of the enzyme involved in the formation of the covalent adduct. 28630348 1 40 with proteins 179:186 arg1 architectures 201:213 diverse architectures 193:213 diverse architectures 193:213 Phosphoglycosyl transferases (PGTs) are integral membrane proteins with diverse architectures that catalyze the formation of polyprenol diphosphate-linked glycans via phosphosugar transfer from a nucleotide diphosphate-sugar to a polyprenol phosphate. 28630348 4 41 theme N-terminal 826:835 arg1 domain 857:862 a predicted N-terminal membrane-associated domain 814:862 a predicted N-terminal membrane-associated domain 814:862 In contrast, less is known about a second, extensive superfamily of PGTs that reveals a core structure with dual domain architecture featuring a C-terminal soluble globular domain and a predicted N-terminal membrane-associated domain. 28630348 1 42 theme polyprenol 246:255 arg1 glycans 276:282 polyprenol diphosphate-linked glycans 246:282 polyprenol diphosphate-linked glycans 246:282 Phosphoglycosyl transferases (PGTs) are integral membrane proteins with diverse architectures that catalyze the formation of polyprenol diphosphate-linked glycans via phosphosugar transfer from a nucleotide diphosphate-sugar to a polyprenol phosphate. 28630348 1 43 theme glycans 276:282 arg1 formation 233:241 the formation 229:241 the formation of polyprenol diphosphate-linked glycans 229:282 Phosphoglycosyl transferases (PGTs) are integral membrane proteins with diverse architectures that catalyze the formation of polyprenol diphosphate-linked glycans via phosphosugar transfer from a nucleotide diphosphate-sugar to a polyprenol phosphate. 28630348 7 44 theme kinetics-based 1299:1312 arg1 approaches 1314:1323 kinetics-based approaches 1299:1323 kinetics-based approaches 1299:1323 Here, we present the mechanistic analysis of PglC, a prototypic dual domain PGT from Campylobacter concisus Using a luminescence-based assay, together with substrate labeling and kinetics-based approaches, complementary experiments were carried out that support a ping-pong mechanism involving a covalent phosphosugar intermediate for PglC. 28630348 8 45 theme adduct 1695:1700 arg1 formation 1669:1677 the formation 1665:1677 the formation of the covalent adduct 1665:1700 Significantly, mass spectrometry-based approaches identified Asp93, which is part of a highly conserved AspGlu dyad found in all dual domain PGTs, as the active-site nucleophile of the enzyme involved in the formation of the covalent adduct. 28630348 0 46 with mechanism 74:82 arg1 intermediate 107:118 a covalent enzyme intermediate 89:118 a covalent enzyme intermediate 89:118 Analysis of a dual domain phosphoglycosyl transferase reveals a ping-pong mechanism with a covalent enzyme intermediate. 28630348 1 47 theme phosphosugar 288:299 arg1 transfer 301:308 phosphosugar transfer 288:308 phosphosugar transfer from a nucleotide diphosphate-sugar to a polyprenol phosphate 288:370 Phosphoglycosyl transferases (PGTs) are integral membrane proteins with diverse architectures that catalyze the formation of polyprenol diphosphate-linked glycans via phosphosugar transfer from a nucleotide diphosphate-sugar to a polyprenol phosphate. 28630348 9 48 theme phosphosugar 1731:1742 arg1 intermediate 1744:1755 a covalent phosphosugar intermediate 1720:1755 a covalent phosphosugar intermediate 1720:1755 The existence of a covalent phosphosugar intermediate provides strong support for a ping-pong mechanism of PglC, differing fundamentally from the ternary complex mechanisms of representative polytopic PGTs. 28630348 7 49 theme mechanistic 1141:1151 arg1 analysis 1153:1160 the mechanistic analysis 1137:1160 the mechanistic analysis of PglC, a prototypic dual domain PGT from Campylobacter concisus 1137:1226 Here, we present the mechanistic analysis of PglC, a prototypic dual domain PGT from Campylobacter concisus Using a luminescence-based assay, together with substrate labeling and kinetics-based approaches, complementary experiments were carried out that support a ping-pong mechanism involving a covalent phosphosugar intermediate for PglC. 28630348 3 50 theme studies 556:562 arg1 superfamily 484:494 The polytopic PGT superfamily 466:494 The polytopic PGT superfamily 466:494 The polytopic PGT superfamily, represented by MraY and WecA, has been the subject of many studies because of its roles in peptidoglycan and O-antigen biosynthesis. 28630348 3 50 theme studies 556:562 arg1 subject 540:546 the subject 536:546 the subject of many studies 536:562 The polytopic PGT superfamily, represented by MraY and WecA, has been the subject of many studies because of its roles in peptidoglycan and O-antigen biosynthesis. 28630348 1 51 theme membrane 170:177 arg1 transferases 137:148 Phosphoglycosyl transferases 121:148 Phosphoglycosyl transferases (PGTs) 121:155 Phosphoglycosyl transferases (PGTs) are integral membrane proteins with diverse architectures that catalyze the formation of polyprenol diphosphate-linked glycans via phosphosugar transfer from a nucleotide diphosphate-sugar to a polyprenol phosphate. 28630348 1 51 theme membrane 170:177 arg1 proteins 179:186 integral membrane proteins 161:186 integral membrane proteins with diverse architectures that catalyze the formation of polyprenol diphosphate-linked glycans via phosphosugar transfer from a nucleotide diphosphate-sugar to a polyprenol phosphate 161:370 Phosphoglycosyl transferases (PGTs) are integral membrane proteins with diverse architectures that catalyze the formation of polyprenol diphosphate-linked glycans via phosphosugar transfer from a nucleotide diphosphate-sugar to a polyprenol phosphate. 28630348 7 52 theme dual 1184:1187 arg1 PglC 1165:1168 PglC 1165:1168 PglC 1165:1168 Here, we present the mechanistic analysis of PglC, a prototypic dual domain PGT from Campylobacter concisus Using a luminescence-based assay, together with substrate labeling and kinetics-based approaches, complementary experiments were carried out that support a ping-pong mechanism involving a covalent phosphosugar intermediate for PglC. 28630348 7 52 theme dual 1184:1187 arg1 PGT 1196:1198 a prototypic dual domain PGT 1171:1198 a prototypic dual domain PGT from Campylobacter concisus 1171:1226 Here, we present the mechanistic analysis of PglC, a prototypic dual domain PGT from Campylobacter concisus Using a luminescence-based assay, together with substrate labeling and kinetics-based approaches, complementary experiments were carried out that support a ping-pong mechanism involving a covalent phosphosugar intermediate for PglC. 28630348 1 53 link diphosphate-linked 257:274 arg1 glycans 276:282 polyprenol diphosphate-linked glycans 246:282 polyprenol diphosphate-linked glycans 246:282 Phosphoglycosyl transferases (PGTs) are integral membrane proteins with diverse architectures that catalyze the formation of polyprenol diphosphate-linked glycans via phosphosugar transfer from a nucleotide diphosphate-sugar to a polyprenol phosphate. 28630348 3 54 theme peptidoglycan 588:600 arg1 biosynthesis 616:627 peptidoglycan and O-antigen biosynthesis 588:627 biosynthesis 616:627 The polytopic PGT superfamily, represented by MraY and WecA, has been the subject of many studies because of its roles in peptidoglycan and O-antigen biosynthesis. 28630348 5 55 theme Campylobacter 916:928 arg1 members 880:886 Representative members 865:886 Representative members of this superfamily 865:906 Representative members of this superfamily are the Campylobacter PglCs, which initiate N-linked glycoprotein biosynthesis and are implicated in virulence and pathogenicity. 28630348 5 55 theme Campylobacter 916:928 arg1 PglCs 930:934 the Campylobacter PglCs 912:934 the Campylobacter PglCs 912:934 Representative members of this superfamily are the Campylobacter PglCs, which initiate N-linked glycoprotein biosynthesis and are implicated in virulence and pathogenicity. 28630348 5 56 gly glycoprotein 961:972 arg1 glycoprotein 961:972 N-linked glycoprotein biosynthesis 952:985 N-linked glycoprotein biosynthesis 952:985 Representative members of this superfamily are the Campylobacter PglCs, which initiate N-linked glycoprotein biosynthesis and are implicated in virulence and pathogenicity. 28630348 5 57 theme N-linked 952:959 arg1 biosynthesis 974:985 N-linked glycoprotein biosynthesis 952:985 N-linked glycoprotein biosynthesis 952:985 Representative members of this superfamily are the Campylobacter PglCs, which initiate N-linked glycoprotein biosynthesis and are implicated in virulence and pathogenicity. 28630348 3 58 theme O-antigen 606:614 arg1 biosynthesis 616:627 peptidoglycan and O-antigen biosynthesis 588:627 biosynthesis 616:627 The polytopic PGT superfamily, represented by MraY and WecA, has been the subject of many studies because of its roles in peptidoglycan and O-antigen biosynthesis. 28630348 5 59 theme glycoprotein 961:972 arg1 biosynthesis 974:985 N-linked glycoprotein biosynthesis 952:985 N-linked glycoprotein biosynthesis 952:985 Representative members of this superfamily are the Campylobacter PglCs, which initiate N-linked glycoprotein biosynthesis and are implicated in virulence and pathogenicity. 28630348 9 60 theme PglC 1810:1813 arg1 mechanism 1797:1805 a ping-pong mechanism 1785:1805 a ping-pong mechanism of PglC, differing fundamentally from the ternary complex mechanisms of representative polytopic PGTs 1785:1907 The existence of a covalent phosphosugar intermediate provides strong support for a ping-pong mechanism of PglC, differing fundamentally from the ternary complex mechanisms of representative polytopic PGTs. 28630348 8 61 theme AspGlu 1565:1570 arg1 dyad 1572:1575 a highly conserved AspGlu dyad 1546:1575 a highly conserved AspGlu dyad found in all dual domain PGTs 1546:1605 Significantly, mass spectrometry-based approaches identified Asp93, which is part of a highly conserved AspGlu dyad found in all dual domain PGTs, as the active-site nucleophile of the enzyme involved in the formation of the covalent adduct. 28630348 4 62 theme core 718:721 arg1 structure 723:731 a core structure 716:731 a core structure with dual domain architecture featuring a C-terminal soluble globular domain and a predicted N-terminal membrane-associated domain 716:862 In contrast, less is known about a second, extensive superfamily of PGTs that reveals a core structure with dual domain architecture featuring a C-terminal soluble globular domain and a predicted N-terminal membrane-associated domain. 28630348 3 63 from roles 579:583 arg1 biosynthesis 616:627 peptidoglycan and O-antigen biosynthesis 588:627 biosynthesis 616:627 The polytopic PGT superfamily, represented by MraY and WecA, has been the subject of many studies because of its roles in peptidoglycan and O-antigen biosynthesis. 28630348 7 64 theme substrate 1276:1284 arg1 labeling 1286:1293 substrate labeling 1276:1293 substrate labeling 1276:1293 Here, we present the mechanistic analysis of PglC, a prototypic dual domain PGT from Campylobacter concisus Using a luminescence-based assay, together with substrate labeling and kinetics-based approaches, complementary experiments were carried out that support a ping-pong mechanism involving a covalent phosphosugar intermediate for PglC. 28630348 7 65 theme phosphosugar 1425:1436 arg1 intermediate 1438:1449 a covalent phosphosugar intermediate 1414:1449 a covalent phosphosugar intermediate for PglC 1414:1458 Here, we present the mechanistic analysis of PglC, a prototypic dual domain PGT from Campylobacter concisus Using a luminescence-based assay, together with substrate labeling and kinetics-based approaches, complementary experiments were carried out that support a ping-pong mechanism involving a covalent phosphosugar intermediate for PglC. 28630348 4 66 theme PGTs 698:701 arg1 superfamily 683:693 a second, extensive superfamily 663:693 a second, extensive superfamily of PGTs that reveals a core structure with dual domain architecture featuring a C-terminal soluble globular domain and a predicted N-terminal membrane-associated domain 663:862 In contrast, less is known about a second, extensive superfamily of PGTs that reveals a core structure with dual domain architecture featuring a C-terminal soluble globular domain and a predicted N-terminal membrane-associated domain. 28630348 6 67 theme domain 1069:1074 arg1 PGTs 1076:1079 dual domain PGTs 1064:1079 dual domain PGTs 1064:1079 Despite the prevalence of dual domain PGTs, their mechanism of action is unknown. 28630348 9 68 theme ternary 1849:1855 arg1 mechanisms 1865:1874 the ternary complex mechanisms 1845:1874 the ternary complex mechanisms of representative polytopic PGTs 1845:1907 The existence of a covalent phosphosugar intermediate provides strong support for a ping-pong mechanism of PglC, differing fundamentally from the ternary complex mechanisms of representative polytopic PGTs. 28630348 8 69 theme domain 1595:1600 arg1 PGTs 1602:1605 all dual domain PGTs 1586:1605 all dual domain PGTs 1586:1605 Significantly, mass spectrometry-based approaches identified Asp93, which is part of a highly conserved AspGlu dyad found in all dual domain PGTs, as the active-site nucleophile of the enzyme involved in the formation of the covalent adduct. 28630348 7 70 dep Campylobacter 1205:1217 arg1 concisus 1219:1226 Campylobacter concisus 1205:1226 Campylobacter concisus 1205:1226 Here, we present the mechanistic analysis of PglC, a prototypic dual domain PGT from Campylobacter concisus Using a luminescence-based assay, together with substrate labeling and kinetics-based approaches, complementary experiments were carried out that support a ping-pong mechanism involving a covalent phosphosugar intermediate for PglC. 28630348 0 71 theme covalent 91:98 arg1 intermediate 107:118 a covalent enzyme intermediate 89:118 a covalent enzyme intermediate 89:118 Analysis of a dual domain phosphoglycosyl transferase reveals a ping-pong mechanism with a covalent enzyme intermediate. 28630348 8 72 located found 1577:1581 arg2 dyad 1572:1575 a highly conserved AspGlu dyad 1546:1575 a highly conserved AspGlu dyad found in all dual domain PGTs 1546:1605 Significantly, mass spectrometry-based approaches identified Asp93, which is part of a highly conserved AspGlu dyad found in all dual domain PGTs, as the active-site nucleophile of the enzyme involved in the formation of the covalent adduct. 28630348 8 72 located found 1577:1581 arg1 PGTs 1602:1605 all dual domain PGTs 1586:1605 all dual domain PGTs 1586:1605 Significantly, mass spectrometry-based approaches identified Asp93, which is part of a highly conserved AspGlu dyad found in all dual domain PGTs, as the active-site nucleophile of the enzyme involved in the formation of the covalent adduct. 28630348 4 73 theme C-terminal 775:784 arg1 domain 803:808 a C-terminal soluble globular domain 773:808 a C-terminal soluble globular domain 773:808 In contrast, less is known about a second, extensive superfamily of PGTs that reveals a core structure with dual domain architecture featuring a C-terminal soluble globular domain and a predicted N-terminal membrane-associated domain. 28630348 9 74 theme representative 1879:1892 arg1 PGTs 1904:1907 representative polytopic PGTs 1879:1907 representative polytopic PGTs 1879:1907 The existence of a covalent phosphosugar intermediate provides strong support for a ping-pong mechanism of PglC, differing fundamentally from the ternary complex mechanisms of representative polytopic PGTs. 28630348 4 75 theme globular 794:801 arg1 domain 803:808 a C-terminal soluble globular domain 773:808 a C-terminal soluble globular domain 773:808 In contrast, less is known about a second, extensive superfamily of PGTs that reveals a core structure with dual domain architecture featuring a C-terminal soluble globular domain and a predicted N-terminal membrane-associated domain. 28630348 2 76 theme overall 434:440 arg1 structure 442:450 overall structure 434:450 overall structure 434:450 There are two PGT superfamilies that differ significantly in overall structure and topology. 28630348 7 77 theme ping-pong 1384:1392 arg1 mechanism 1394:1402 a ping-pong mechanism 1382:1402 a ping-pong mechanism involving a covalent phosphosugar intermediate for PglC 1382:1458 Here, we present the mechanistic analysis of PglC, a prototypic dual domain PGT from Campylobacter concisus Using a luminescence-based assay, together with substrate labeling and kinetics-based approaches, complementary experiments were carried out that support a ping-pong mechanism involving a covalent phosphosugar intermediate for PglC. 28630348 9 78 theme PGTs 1904:1907 arg1 mechanisms 1865:1874 the ternary complex mechanisms 1845:1874 the ternary complex mechanisms of representative polytopic PGTs 1845:1907 The existence of a covalent phosphosugar intermediate provides strong support for a ping-pong mechanism of PglC, differing fundamentally from the ternary complex mechanisms of representative polytopic PGTs. 28630348 4 79 theme domain 743:748 arg1 architecture 750:761 dual domain architecture 738:761 dual domain architecture featuring a C-terminal soluble globular domain and a predicted N-terminal membrane-associated domain 738:862 In contrast, less is known about a second, extensive superfamily of PGTs that reveals a core structure with dual domain architecture featuring a C-terminal soluble globular domain and a predicted N-terminal membrane-associated domain. 28630348 3 80 theme PGT 480:482 arg1 superfamily 484:494 The polytopic PGT superfamily 466:494 The polytopic PGT superfamily 466:494 The polytopic PGT superfamily, represented by MraY and WecA, has been the subject of many studies because of its roles in peptidoglycan and O-antigen biosynthesis. 28630348 3 80 theme PGT 480:482 arg1 subject 540:546 the subject 536:546 the subject of many studies 536:562 The polytopic PGT superfamily, represented by MraY and WecA, has been the subject of many studies because of its roles in peptidoglycan and O-antigen biosynthesis. 28630348 0 81 theme dual 14:17 arg1 transferase 42:52 a dual domain phosphoglycosyl transferase 12:52 a dual domain phosphoglycosyl transferase 12:52 Analysis of a dual domain phosphoglycosyl transferase reveals a ping-pong mechanism with a covalent enzyme intermediate. 28630348 7 82 theme domain 1189:1194 arg1 PglC 1165:1168 PglC 1165:1168 PglC 1165:1168 Here, we present the mechanistic analysis of PglC, a prototypic dual domain PGT from Campylobacter concisus Using a luminescence-based assay, together with substrate labeling and kinetics-based approaches, complementary experiments were carried out that support a ping-pong mechanism involving a covalent phosphosugar intermediate for PglC. 28630348 7 82 theme domain 1189:1194 arg1 PGT 1196:1198 a prototypic dual domain PGT 1171:1198 a prototypic dual domain PGT from Campylobacter concisus 1171:1226 Here, we present the mechanistic analysis of PglC, a prototypic dual domain PGT from Campylobacter concisus Using a luminescence-based assay, together with substrate labeling and kinetics-based approaches, complementary experiments were carried out that support a ping-pong mechanism involving a covalent phosphosugar intermediate for PglC. 28630348 4 83 dep second 665:670 arg1 extensive 673:681 extensive 673:681 extensive 673:681 In contrast, less is known about a second, extensive superfamily of PGTs that reveals a core structure with dual domain architecture featuring a C-terminal soluble globular domain and a predicted N-terminal membrane-associated domain. 28630348 6 84 theme action 1101:1106 arg1 mechanism 1088:1096 their mechanism 1082:1096 their mechanism of action 1082:1106 Despite the prevalence of dual domain PGTs, their mechanism of action is unknown. 28630348 4 85 theme membrane-associated 837:855 arg1 domain 857:862 a predicted N-terminal membrane-associated domain 814:862 a predicted N-terminal membrane-associated domain 814:862 In contrast, less is known about a second, extensive superfamily of PGTs that reveals a core structure with dual domain architecture featuring a C-terminal soluble globular domain and a predicted N-terminal membrane-associated domain. 28630348 0 86 theme enzyme 100:105 arg1 intermediate 107:118 a covalent enzyme intermediate 89:118 a covalent enzyme intermediate 89:118 Analysis of a dual domain phosphoglycosyl transferase reveals a ping-pong mechanism with a covalent enzyme intermediate. 28630348 7 87 theme prototypic 1173:1182 arg1 PglC 1165:1168 PglC 1165:1168 PglC 1165:1168 Here, we present the mechanistic analysis of PglC, a prototypic dual domain PGT from Campylobacter concisus Using a luminescence-based assay, together with substrate labeling and kinetics-based approaches, complementary experiments were carried out that support a ping-pong mechanism involving a covalent phosphosugar intermediate for PglC. 28630348 7 87 theme prototypic 1173:1182 arg1 PGT 1196:1198 a prototypic dual domain PGT 1171:1198 a prototypic dual domain PGT from Campylobacter concisus 1171:1226 Here, we present the mechanistic analysis of PglC, a prototypic dual domain PGT from Campylobacter concisus Using a luminescence-based assay, together with substrate labeling and kinetics-based approaches, complementary experiments were carried out that support a ping-pong mechanism involving a covalent phosphosugar intermediate for PglC. 28630348 7 88 theme complementary 1326:1338 arg1 experiments 1340:1350 complementary experiments 1326:1350 complementary experiments 1326:1350 Here, we present the mechanistic analysis of PglC, a prototypic dual domain PGT from Campylobacter concisus Using a luminescence-based assay, together with substrate labeling and kinetics-based approaches, complementary experiments were carried out that support a ping-pong mechanism involving a covalent phosphosugar intermediate for PglC. 28630348 8 89 theme covalent 1686:1693 arg1 adduct 1695:1700 the covalent adduct 1682:1700 the covalent adduct 1682:1700 Significantly, mass spectrometry-based approaches identified Asp93, which is part of a highly conserved AspGlu dyad found in all dual domain PGTs, as the active-site nucleophile of the enzyme involved in the formation of the covalent adduct. 28630348 4 90 theme predicted 816:824 arg1 domain 857:862 a predicted N-terminal membrane-associated domain 814:862 a predicted N-terminal membrane-associated domain 814:862 In contrast, less is known about a second, extensive superfamily of PGTs that reveals a core structure with dual domain architecture featuring a C-terminal soluble globular domain and a predicted N-terminal membrane-associated domain. 28630348 3 91 theme many 551:554 arg1 studies 556:562 many studies 551:562 many studies 551:562 The polytopic PGT superfamily, represented by MraY and WecA, has been the subject of many studies because of its roles in peptidoglycan and O-antigen biosynthesis. 28630348 1 92 theme diphosphate-linked 257:274 arg1 glycans 276:282 polyprenol diphosphate-linked glycans 246:282 polyprenol diphosphate-linked glycans 246:282 Phosphoglycosyl transferases (PGTs) are integral membrane proteins with diverse architectures that catalyze the formation of polyprenol diphosphate-linked glycans via phosphosugar transfer from a nucleotide diphosphate-sugar to a polyprenol phosphate. 28433058 3 0 theme Au 724:725 arg1 nanowires 727:735 The ultrathin Au nanowires 710:735 The ultrathin Au nanowires 710:735 The ultrathin Au nanowires have a one-dimensional structure and were easily grafted with an abundant amount of L-Cys for the enrichment of glycopeptides. 28433058 2 1 theme Au 626:627 arg1 nanowires 629:637 ultrathin Au nanowires 616:637 ultrathin Au nanowires 616:637 In this study, a novel ultrathin Au nanowire assisted zwitterionic hydrophilic magnetic graphene oxide (GO-Fe3O4/SiO2/AuNWs/L-Cys) was synthesized with the good biocompatibility of GO, strong magnetic responses of Fe3O4, large surface area of ultrathin Au nanowires and excellent hydrophilicity of L-Cys via four simple and rapid steps. 28433058 0 2 theme specific 89:96 arg1 enrichment 98:107 highly specific enrichment 82:107 highly specific enrichment of N-linked glycopeptides 82:133 Ultrathin Au nanowires assisted magnetic graphene-silica ZIC-HILIC composites for highly specific enrichment of N-linked glycopeptides. 28433058 3 3 theme glycopeptides 849:861 arg1 enrichment 835:844 the enrichment 831:844 the enrichment of glycopeptides 831:861 The ultrathin Au nanowires have a one-dimensional structure and were easily grafted with an abundant amount of L-Cys for the enrichment of glycopeptides. 28433058 2 4 theme ultrathin 616:624 arg1 nanowires 629:637 ultrathin Au nanowires 616:637 ultrathin Au nanowires 616:637 In this study, a novel ultrathin Au nanowire assisted zwitterionic hydrophilic magnetic graphene oxide (GO-Fe3O4/SiO2/AuNWs/L-Cys) was synthesized with the good biocompatibility of GO, strong magnetic responses of Fe3O4, large surface area of ultrathin Au nanowires and excellent hydrophilicity of L-Cys via four simple and rapid steps. 28433058 1 5 theme glycopeptides 265:277 arg1 abundance 252:260 the low abundance 244:260 the low abundance of glycopeptides in natural samples 244:296 Protein glycosylation has been proven to participate in a variety of complex biological processes; however, the low abundance of glycopeptides in natural samples makes it essential to develop methods to isolate and enrich glycopeptides. 28433058 0 6 theme N-linked 112:119 arg1 glycopeptides 121:133 N-linked glycopeptides 112:133 N-linked glycopeptides 112:133 Ultrathin Au nanowires assisted magnetic graphene-silica ZIC-HILIC composites for highly specific enrichment of N-linked glycopeptides. 28433058 7 7 gly glycoproteins 1292:1304 arg1 glycoproteins 1292:1304 467 glycoproteins 1288:1304 467 glycoproteins 1288:1304 A total of 793 glycopeptides from 467 glycoproteins were identified in three replicate analyses of 40 μg of mouse liver proteins. 28433058 8 8 theme great 1413:1417 arg1 potential 1419:1427 the great potential 1409:1427 the great potential of GO-Fe3O4/SiO2/AuNWs/L-Cys composites for the analysis of glycoproteins 1409:1501 The results demonstrated the great potential of GO-Fe3O4/SiO2/AuNWs/L-Cys composites for the analysis of glycoproteins. 28433058 8 9 theme GO-Fe3O4/SiO2/AuNWs/L-Cys 1432:1456 arg1 composites 1458:1467 GO-Fe3O4/SiO2/AuNWs/L-Cys composites 1432:1467 GO-Fe3O4/SiO2/AuNWs/L-Cys composites 1432:1467 The results demonstrated the great potential of GO-Fe3O4/SiO2/AuNWs/L-Cys composites for the analysis of glycoproteins. 28433058 4 10 from digest 986:991 arg1 glycopeptides 955:967 26 glycopeptides 952:967 26 glycopeptides from a human IgG digest 952:991 After the GO-Fe3O4/SiO2/AuNWs/L-Cys composites were applied to glycopeptide enrichment, 26 glycopeptides from a human IgG digest could be identified, with a detection limit as low as 10 fmol. 28433058 2 11 theme GO 554:555 arg1 responses 574:582 strong magnetic responses 558:582 strong magnetic responses of Fe3O4 558:591 In this study, a novel ultrathin Au nanowire assisted zwitterionic hydrophilic magnetic graphene oxide (GO-Fe3O4/SiO2/AuNWs/L-Cys) was synthesized with the good biocompatibility of GO, strong magnetic responses of Fe3O4, large surface area of ultrathin Au nanowires and excellent hydrophilicity of L-Cys via four simple and rapid steps. 28433058 2 11 theme GO 554:555 arg1 area 608:611 large surface area 594:611 large surface area of ultrathin Au nanowires 594:637 In this study, a novel ultrathin Au nanowire assisted zwitterionic hydrophilic magnetic graphene oxide (GO-Fe3O4/SiO2/AuNWs/L-Cys) was synthesized with the good biocompatibility of GO, strong magnetic responses of Fe3O4, large surface area of ultrathin Au nanowires and excellent hydrophilicity of L-Cys via four simple and rapid steps. 28433058 2 11 theme GO 554:555 arg1 biocompatibility 534:549 the good biocompatibility 525:549 the good biocompatibility of GO 525:555 In this study, a novel ultrathin Au nanowire assisted zwitterionic hydrophilic magnetic graphene oxide (GO-Fe3O4/SiO2/AuNWs/L-Cys) was synthesized with the good biocompatibility of GO, strong magnetic responses of Fe3O4, large surface area of ultrathin Au nanowires and excellent hydrophilicity of L-Cys via four simple and rapid steps. 28433058 2 11 theme GO 554:555 arg1 hydrophilicity 653:666 excellent hydrophilicity 643:666 excellent hydrophilicity of L-Cys 643:675 In this study, a novel ultrathin Au nanowire assisted zwitterionic hydrophilic magnetic graphene oxide (GO-Fe3O4/SiO2/AuNWs/L-Cys) was synthesized with the good biocompatibility of GO, strong magnetic responses of Fe3O4, large surface area of ultrathin Au nanowires and excellent hydrophilicity of L-Cys via four simple and rapid steps. 28433058 2 12 theme L-Cys 671:675 arg1 responses 574:582 strong magnetic responses 558:582 strong magnetic responses of Fe3O4 558:591 In this study, a novel ultrathin Au nanowire assisted zwitterionic hydrophilic magnetic graphene oxide (GO-Fe3O4/SiO2/AuNWs/L-Cys) was synthesized with the good biocompatibility of GO, strong magnetic responses of Fe3O4, large surface area of ultrathin Au nanowires and excellent hydrophilicity of L-Cys via four simple and rapid steps. 28433058 2 12 theme L-Cys 671:675 arg1 area 608:611 large surface area 594:611 large surface area of ultrathin Au nanowires 594:637 In this study, a novel ultrathin Au nanowire assisted zwitterionic hydrophilic magnetic graphene oxide (GO-Fe3O4/SiO2/AuNWs/L-Cys) was synthesized with the good biocompatibility of GO, strong magnetic responses of Fe3O4, large surface area of ultrathin Au nanowires and excellent hydrophilicity of L-Cys via four simple and rapid steps. 28433058 2 12 theme L-Cys 671:675 arg1 biocompatibility 534:549 the good biocompatibility 525:549 the good biocompatibility of GO 525:555 In this study, a novel ultrathin Au nanowire assisted zwitterionic hydrophilic magnetic graphene oxide (GO-Fe3O4/SiO2/AuNWs/L-Cys) was synthesized with the good biocompatibility of GO, strong magnetic responses of Fe3O4, large surface area of ultrathin Au nanowires and excellent hydrophilicity of L-Cys via four simple and rapid steps. 28433058 2 12 theme L-Cys 671:675 arg1 hydrophilicity 653:666 excellent hydrophilicity 643:666 excellent hydrophilicity of L-Cys 643:675 In this study, a novel ultrathin Au nanowire assisted zwitterionic hydrophilic magnetic graphene oxide (GO-Fe3O4/SiO2/AuNWs/L-Cys) was synthesized with the good biocompatibility of GO, strong magnetic responses of Fe3O4, large surface area of ultrathin Au nanowires and excellent hydrophilicity of L-Cys via four simple and rapid steps. 28433058 4 13 theme detection 1021:1029 arg1 limit 1031:1035 a detection limit 1019:1035 a detection limit as low as 10 fmol 1019:1053 After the GO-Fe3O4/SiO2/AuNWs/L-Cys composites were applied to glycopeptide enrichment, 26 glycopeptides from a human IgG digest could be identified, with a detection limit as low as 10 fmol. 28433058 1 14 theme natural 282:288 arg1 samples 290:296 natural samples 282:296 natural samples 282:296 Protein glycosylation has been proven to participate in a variety of complex biological processes; however, the low abundance of glycopeptides in natural samples makes it essential to develop methods to isolate and enrich glycopeptides. 28433058 3 15 contain have 737:740 arg2 structure 760:768 a one-dimensional structure 742:768 a one-dimensional structure 742:768 The ultrathin Au nanowires have a one-dimensional structure and were easily grafted with an abundant amount of L-Cys for the enrichment of glycopeptides. 28433058 3 15 contain have 737:740 arg1 nanowires 727:735 The ultrathin Au nanowires 710:735 The ultrathin Au nanowires 710:735 The ultrathin Au nanowires have a one-dimensional structure and were easily grafted with an abundant amount of L-Cys for the enrichment of glycopeptides. 28433058 2 16 theme assisted 418:425 arg1 GO-Fe3O4/SiO2/AuNWs/L-Cys 477:501 assisted zwitterionic hydrophilic magnetic graphene oxide (GO-Fe3O4/SiO2/AuNWs/L-Cys) 418:502 a novel ultrathin Au nanowire assisted zwitterionic hydrophilic magnetic graphene oxide (GO-Fe3O4/SiO2/AuNWs/L-Cys) 388:502 In this study, a novel ultrathin Au nanowire assisted zwitterionic hydrophilic magnetic graphene oxide (GO-Fe3O4/SiO2/AuNWs/L-Cys) was synthesized with the good biocompatibility of GO, strong magnetic responses of Fe3O4, large surface area of ultrathin Au nanowires and excellent hydrophilicity of L-Cys via four simple and rapid steps. 28433058 2 17 theme ultrathin 396:404 arg1 nanowire 409:416 a novel ultrathin Au nanowire 388:416 a novel ultrathin Au nanowire assisted zwitterionic hydrophilic magnetic graphene oxide (GO-Fe3O4/SiO2/AuNWs/L-Cys) 388:502 In this study, a novel ultrathin Au nanowire assisted zwitterionic hydrophilic magnetic graphene oxide (GO-Fe3O4/SiO2/AuNWs/L-Cys) was synthesized with the good biocompatibility of GO, strong magnetic responses of Fe3O4, large surface area of ultrathin Au nanowires and excellent hydrophilicity of L-Cys via four simple and rapid steps. 28433058 0 18 theme glycopeptides 121:133 arg1 enrichment 98:107 highly specific enrichment 82:107 highly specific enrichment of N-linked glycopeptides 82:133 Ultrathin Au nanowires assisted magnetic graphene-silica ZIC-HILIC composites for highly specific enrichment of N-linked glycopeptides. 28433058 2 19 theme excellent 643:651 arg1 hydrophilicity 653:666 excellent hydrophilicity 643:666 excellent hydrophilicity of L-Cys 643:675 In this study, a novel ultrathin Au nanowire assisted zwitterionic hydrophilic magnetic graphene oxide (GO-Fe3O4/SiO2/AuNWs/L-Cys) was synthesized with the good biocompatibility of GO, strong magnetic responses of Fe3O4, large surface area of ultrathin Au nanowires and excellent hydrophilicity of L-Cys via four simple and rapid steps. 28433058 1 20 gly glycopeptides 265:277 arg2 glycopeptides 265:277 glycopeptides 265:277 glycopeptides 265:277 Protein glycosylation has been proven to participate in a variety of complex biological processes; however, the low abundance of glycopeptides in natural samples makes it essential to develop methods to isolate and enrich glycopeptides. 28433058 2 21 theme graphene 461:468 arg1 GO-Fe3O4/SiO2/AuNWs/L-Cys 477:501 assisted zwitterionic hydrophilic magnetic graphene oxide (GO-Fe3O4/SiO2/AuNWs/L-Cys) 418:502 a novel ultrathin Au nanowire assisted zwitterionic hydrophilic magnetic graphene oxide (GO-Fe3O4/SiO2/AuNWs/L-Cys) 388:502 In this study, a novel ultrathin Au nanowire assisted zwitterionic hydrophilic magnetic graphene oxide (GO-Fe3O4/SiO2/AuNWs/L-Cys) was synthesized with the good biocompatibility of GO, strong magnetic responses of Fe3O4, large surface area of ultrathin Au nanowires and excellent hydrophilicity of L-Cys via four simple and rapid steps. 28433058 1 22 gly glycopeptides 358:370 arg2 glycopeptides 358:370 glycopeptides 358:370 glycopeptides 358:370 Protein glycosylation has been proven to participate in a variety of complex biological processes; however, the low abundance of glycopeptides in natural samples makes it essential to develop methods to isolate and enrich glycopeptides. 28433058 2 23 theme novel 390:394 arg1 nanowire 409:416 a novel ultrathin Au nanowire 388:416 a novel ultrathin Au nanowire assisted zwitterionic hydrophilic magnetic graphene oxide (GO-Fe3O4/SiO2/AuNWs/L-Cys) 388:502 In this study, a novel ultrathin Au nanowire assisted zwitterionic hydrophilic magnetic graphene oxide (GO-Fe3O4/SiO2/AuNWs/L-Cys) was synthesized with the good biocompatibility of GO, strong magnetic responses of Fe3O4, large surface area of ultrathin Au nanowires and excellent hydrophilicity of L-Cys via four simple and rapid steps. 28433058 2 24 theme oxide 470:474 arg1 GO-Fe3O4/SiO2/AuNWs/L-Cys 477:501 assisted zwitterionic hydrophilic magnetic graphene oxide (GO-Fe3O4/SiO2/AuNWs/L-Cys) 418:502 a novel ultrathin Au nanowire assisted zwitterionic hydrophilic magnetic graphene oxide (GO-Fe3O4/SiO2/AuNWs/L-Cys) 388:502 In this study, a novel ultrathin Au nanowire assisted zwitterionic hydrophilic magnetic graphene oxide (GO-Fe3O4/SiO2/AuNWs/L-Cys) was synthesized with the good biocompatibility of GO, strong magnetic responses of Fe3O4, large surface area of ultrathin Au nanowires and excellent hydrophilicity of L-Cys via four simple and rapid steps. 28433058 4 25 theme GO-Fe3O4/SiO2/AuNWs/L-Cys 874:898 arg1 composites 900:909 the GO-Fe3O4/SiO2/AuNWs/L-Cys composites 870:909 the GO-Fe3O4/SiO2/AuNWs/L-Cys composites 870:909 After the GO-Fe3O4/SiO2/AuNWs/L-Cys composites were applied to glycopeptide enrichment, 26 glycopeptides from a human IgG digest could be identified, with a detection limit as low as 10 fmol. 28433058 2 26 theme rapid 697:701 arg1 steps 703:707 four simple and rapid steps 681:707 four simple and rapid steps 681:707 In this study, a novel ultrathin Au nanowire assisted zwitterionic hydrophilic magnetic graphene oxide (GO-Fe3O4/SiO2/AuNWs/L-Cys) was synthesized with the good biocompatibility of GO, strong magnetic responses of Fe3O4, large surface area of ultrathin Au nanowires and excellent hydrophilicity of L-Cys via four simple and rapid steps. 28433058 7 27 dep analyses 1341:1348 arg1 replicate 1331:1339 replicate 1331:1339 replicate 1331:1339 A total of 793 glycopeptides from 467 glycoproteins were identified in three replicate analyses of 40 μg of mouse liver proteins. 28433058 2 28 theme large 594:598 arg1 area 608:611 large surface area 594:611 large surface area of ultrathin Au nanowires 594:637 In this study, a novel ultrathin Au nanowire assisted zwitterionic hydrophilic magnetic graphene oxide (GO-Fe3O4/SiO2/AuNWs/L-Cys) was synthesized with the good biocompatibility of GO, strong magnetic responses of Fe3O4, large surface area of ultrathin Au nanowires and excellent hydrophilicity of L-Cys via four simple and rapid steps. 28433058 0 29 theme Ultrathin 0:8 arg1 Au 10:11 Ultrathin Au 0:11 Ultrathin Au 0:11 Ultrathin Au nanowires assisted magnetic graphene-silica ZIC-HILIC composites for highly specific enrichment of N-linked glycopeptides. 28433058 4 30 theme human 976:980 arg1 digest 986:991 a human IgG digest 974:991 a human IgG digest 974:991 After the GO-Fe3O4/SiO2/AuNWs/L-Cys composites were applied to glycopeptide enrichment, 26 glycopeptides from a human IgG digest could be identified, with a detection limit as low as 10 fmol. 28433058 2 31 theme nanowires 629:637 arg1 responses 574:582 strong magnetic responses 558:582 strong magnetic responses of Fe3O4 558:591 In this study, a novel ultrathin Au nanowire assisted zwitterionic hydrophilic magnetic graphene oxide (GO-Fe3O4/SiO2/AuNWs/L-Cys) was synthesized with the good biocompatibility of GO, strong magnetic responses of Fe3O4, large surface area of ultrathin Au nanowires and excellent hydrophilicity of L-Cys via four simple and rapid steps. 28433058 2 31 theme nanowires 629:637 arg1 area 608:611 large surface area 594:611 large surface area of ultrathin Au nanowires 594:637 In this study, a novel ultrathin Au nanowire assisted zwitterionic hydrophilic magnetic graphene oxide (GO-Fe3O4/SiO2/AuNWs/L-Cys) was synthesized with the good biocompatibility of GO, strong magnetic responses of Fe3O4, large surface area of ultrathin Au nanowires and excellent hydrophilicity of L-Cys via four simple and rapid steps. 28433058 2 31 theme nanowires 629:637 arg1 biocompatibility 534:549 the good biocompatibility 525:549 the good biocompatibility of GO 525:555 In this study, a novel ultrathin Au nanowire assisted zwitterionic hydrophilic magnetic graphene oxide (GO-Fe3O4/SiO2/AuNWs/L-Cys) was synthesized with the good biocompatibility of GO, strong magnetic responses of Fe3O4, large surface area of ultrathin Au nanowires and excellent hydrophilicity of L-Cys via four simple and rapid steps. 28433058 2 31 theme nanowires 629:637 arg1 hydrophilicity 653:666 excellent hydrophilicity 643:666 excellent hydrophilicity of L-Cys 643:675 In this study, a novel ultrathin Au nanowire assisted zwitterionic hydrophilic magnetic graphene oxide (GO-Fe3O4/SiO2/AuNWs/L-Cys) was synthesized with the good biocompatibility of GO, strong magnetic responses of Fe3O4, large surface area of ultrathin Au nanowires and excellent hydrophilicity of L-Cys via four simple and rapid steps. 28433058 8 32 gly glycoproteins 1489:1501 arg1 glycoproteins 1489:1501 glycoproteins 1489:1501 glycoproteins 1489:1501 The results demonstrated the great potential of GO-Fe3O4/SiO2/AuNWs/L-Cys composites for the analysis of glycoproteins. 28433058 5 33 theme binding 1136:1142 arg1 150 μg mg-1 1154:1164 150 μg mg-1 1154:1164 150 μg mg-1 1154:1164 Due to the abundant amount of grafted L-Cys, the composites also showed a large binding capacity (150 μg mg-1). 28433058 5 33 theme binding 1136:1142 arg1 capacity 1144:1151 a large binding capacity 1128:1151 a large binding capacity (150 μg mg-1) 1128:1165 Due to the abundant amount of grafted L-Cys, the composites also showed a large binding capacity (150 μg mg-1). 28433058 1 34 theme complex 205:211 arg1 processes 224:232 complex biological processes 205:232 complex biological processes 205:232 Protein glycosylation has been proven to participate in a variety of complex biological processes; however, the low abundance of glycopeptides in natural samples makes it essential to develop methods to isolate and enrich glycopeptides. 28433058 0 35 theme assisted 23:30 arg1 composites 67:76 assisted magnetic graphene-silica ZIC-HILIC composites 23:76 assisted magnetic graphene-silica ZIC-HILIC composites for highly specific enrichment of N-linked glycopeptides 23:133 Ultrathin Au nanowires assisted magnetic graphene-silica ZIC-HILIC composites for highly specific enrichment of N-linked glycopeptides. 28433058 2 36 theme simple 686:691 arg1 steps 703:707 four simple and rapid steps 681:707 four simple and rapid steps 681:707 In this study, a novel ultrathin Au nanowire assisted zwitterionic hydrophilic magnetic graphene oxide (GO-Fe3O4/SiO2/AuNWs/L-Cys) was synthesized with the good biocompatibility of GO, strong magnetic responses of Fe3O4, large surface area of ultrathin Au nanowires and excellent hydrophilicity of L-Cys via four simple and rapid steps. 28433058 0 37 gly glycopeptides 121:133 arg2 glycopeptides 121:133 N-linked glycopeptides 112:133 N-linked glycopeptides 112:133 Ultrathin Au nanowires assisted magnetic graphene-silica ZIC-HILIC composites for highly specific enrichment of N-linked glycopeptides. 28433058 6 38 theme biological 1234:1243 arg1 samples 1245:1251 real biological samples 1229:1251 real biological samples 1229:1251 Furthermore, the composites were applied for the analysis of real biological samples. 28433058 1 39 theme biological 213:222 arg1 processes 224:232 complex biological processes 205:232 complex biological processes 205:232 Protein glycosylation has been proven to participate in a variety of complex biological processes; however, the low abundance of glycopeptides in natural samples makes it essential to develop methods to isolate and enrich glycopeptides. 28433058 2 40 theme hydrophilic 440:450 arg1 GO-Fe3O4/SiO2/AuNWs/L-Cys 477:501 assisted zwitterionic hydrophilic magnetic graphene oxide (GO-Fe3O4/SiO2/AuNWs/L-Cys) 418:502 a novel ultrathin Au nanowire assisted zwitterionic hydrophilic magnetic graphene oxide (GO-Fe3O4/SiO2/AuNWs/L-Cys) 388:502 In this study, a novel ultrathin Au nanowire assisted zwitterionic hydrophilic magnetic graphene oxide (GO-Fe3O4/SiO2/AuNWs/L-Cys) was synthesized with the good biocompatibility of GO, strong magnetic responses of Fe3O4, large surface area of ultrathin Au nanowires and excellent hydrophilicity of L-Cys via four simple and rapid steps. 28433058 5 41 theme large 1130:1134 arg1 150 μg mg-1 1154:1164 150 μg mg-1 1154:1164 150 μg mg-1 1154:1164 Due to the abundant amount of grafted L-Cys, the composites also showed a large binding capacity (150 μg mg-1). 28433058 5 41 theme large 1130:1134 arg1 capacity 1144:1151 a large binding capacity 1128:1151 a large binding capacity (150 μg mg-1) 1128:1165 Due to the abundant amount of grafted L-Cys, the composites also showed a large binding capacity (150 μg mg-1). 28433058 3 42 gly glycopeptides 849:861 arg2 glycopeptides 849:861 glycopeptides 849:861 glycopeptides 849:861 The ultrathin Au nanowires have a one-dimensional structure and were easily grafted with an abundant amount of L-Cys for the enrichment of glycopeptides. 28433058 1 43 theme processes 224:232 arg1 processes 224:232 complex biological processes 205:232 complex biological processes 205:232 Protein glycosylation has been proven to participate in a variety of complex biological processes; however, the low abundance of glycopeptides in natural samples makes it essential to develop methods to isolate and enrich glycopeptides. 28433058 1 43 theme processes 224:232 arg1 variety 194:200 a variety 192:200 a variety of complex biological processes 192:232 Protein glycosylation has been proven to participate in a variety of complex biological processes; however, the low abundance of glycopeptides in natural samples makes it essential to develop methods to isolate and enrich glycopeptides. 28433058 0 44 theme graphene-silica 41:55 arg1 composites 67:76 assisted magnetic graphene-silica ZIC-HILIC composites 23:76 assisted magnetic graphene-silica ZIC-HILIC composites for highly specific enrichment of N-linked glycopeptides 23:133 Ultrathin Au nanowires assisted magnetic graphene-silica ZIC-HILIC composites for highly specific enrichment of N-linked glycopeptides. 28433058 2 45 theme magnetic 565:572 arg1 responses 574:582 strong magnetic responses 558:582 strong magnetic responses of Fe3O4 558:591 In this study, a novel ultrathin Au nanowire assisted zwitterionic hydrophilic magnetic graphene oxide (GO-Fe3O4/SiO2/AuNWs/L-Cys) was synthesized with the good biocompatibility of GO, strong magnetic responses of Fe3O4, large surface area of ultrathin Au nanowires and excellent hydrophilicity of L-Cys via four simple and rapid steps. 28433058 5 46 theme grafted 1086:1092 arg1 L-Cys 1094:1098 grafted L-Cys 1086:1098 grafted L-Cys 1086:1098 Due to the abundant amount of grafted L-Cys, the composites also showed a large binding capacity (150 μg mg-1). 28433058 2 47 dep nanowire 409:416 arg1 GO-Fe3O4/SiO2/AuNWs/L-Cys 477:501 assisted zwitterionic hydrophilic magnetic graphene oxide (GO-Fe3O4/SiO2/AuNWs/L-Cys) 418:502 a novel ultrathin Au nanowire assisted zwitterionic hydrophilic magnetic graphene oxide (GO-Fe3O4/SiO2/AuNWs/L-Cys) 388:502 In this study, a novel ultrathin Au nanowire assisted zwitterionic hydrophilic magnetic graphene oxide (GO-Fe3O4/SiO2/AuNWs/L-Cys) was synthesized with the good biocompatibility of GO, strong magnetic responses of Fe3O4, large surface area of ultrathin Au nanowires and excellent hydrophilicity of L-Cys via four simple and rapid steps. 28433058 0 48 theme magnetic 32:39 arg1 composites 67:76 assisted magnetic graphene-silica ZIC-HILIC composites 23:76 assisted magnetic graphene-silica ZIC-HILIC composites for highly specific enrichment of N-linked glycopeptides 23:133 Ultrathin Au nanowires assisted magnetic graphene-silica ZIC-HILIC composites for highly specific enrichment of N-linked glycopeptides. 28433058 2 49 theme strong 558:563 arg1 responses 574:582 strong magnetic responses 558:582 strong magnetic responses of Fe3O4 558:591 In this study, a novel ultrathin Au nanowire assisted zwitterionic hydrophilic magnetic graphene oxide (GO-Fe3O4/SiO2/AuNWs/L-Cys) was synthesized with the good biocompatibility of GO, strong magnetic responses of Fe3O4, large surface area of ultrathin Au nanowires and excellent hydrophilicity of L-Cys via four simple and rapid steps. 28433058 5 50 theme L-Cys 1094:1098 arg1 amount 1076:1081 the abundant amount 1063:1081 the abundant amount of grafted L-Cys 1063:1098 Due to the abundant amount of grafted L-Cys, the composites also showed a large binding capacity (150 μg mg-1). 28433058 5 50 theme L-Cys 1094:1098 arg1 L-Cys 1094:1098 grafted L-Cys 1086:1098 grafted L-Cys 1086:1098 Due to the abundant amount of grafted L-Cys, the composites also showed a large binding capacity (150 μg mg-1). 28433058 2 51 theme magnetic 452:459 arg1 GO-Fe3O4/SiO2/AuNWs/L-Cys 477:501 assisted zwitterionic hydrophilic magnetic graphene oxide (GO-Fe3O4/SiO2/AuNWs/L-Cys) 418:502 a novel ultrathin Au nanowire assisted zwitterionic hydrophilic magnetic graphene oxide (GO-Fe3O4/SiO2/AuNWs/L-Cys) 388:502 In this study, a novel ultrathin Au nanowire assisted zwitterionic hydrophilic magnetic graphene oxide (GO-Fe3O4/SiO2/AuNWs/L-Cys) was synthesized with the good biocompatibility of GO, strong magnetic responses of Fe3O4, large surface area of ultrathin Au nanowires and excellent hydrophilicity of L-Cys via four simple and rapid steps. 28433058 7 52 gly glycopeptides 1269:1281 arg2 glycopeptides 1269:1281 793 glycopeptides 1265:1281 793 glycopeptides from 467 glycoproteins 1265:1304 A total of 793 glycopeptides from 467 glycoproteins were identified in three replicate analyses of 40 μg of mouse liver proteins. 28433058 7 52 gly glycopeptides 1269:1281 arg1 glycoproteins 1292:1304 467 glycoproteins 1288:1304 467 glycoproteins 1288:1304 A total of 793 glycopeptides from 467 glycoproteins were identified in three replicate analyses of 40 μg of mouse liver proteins. 28433058 2 53 theme Au 406:407 arg1 nanowire 409:416 a novel ultrathin Au nanowire 388:416 a novel ultrathin Au nanowire assisted zwitterionic hydrophilic magnetic graphene oxide (GO-Fe3O4/SiO2/AuNWs/L-Cys) 388:502 In this study, a novel ultrathin Au nanowire assisted zwitterionic hydrophilic magnetic graphene oxide (GO-Fe3O4/SiO2/AuNWs/L-Cys) was synthesized with the good biocompatibility of GO, strong magnetic responses of Fe3O4, large surface area of ultrathin Au nanowires and excellent hydrophilicity of L-Cys via four simple and rapid steps. 28433058 4 54 theme low 1040:1042 arg1 limit 1031:1035 a detection limit 1019:1035 a detection limit as low as 10 fmol 1019:1053 After the GO-Fe3O4/SiO2/AuNWs/L-Cys composites were applied to glycopeptide enrichment, 26 glycopeptides from a human IgG digest could be identified, with a detection limit as low as 10 fmol. 28433058 3 55 theme abundant 802:809 arg1 L-Cys 821:825 L-Cys 821:825 L-Cys 821:825 The ultrathin Au nanowires have a one-dimensional structure and were easily grafted with an abundant amount of L-Cys for the enrichment of glycopeptides. 28433058 3 55 theme abundant 802:809 arg1 amount 811:816 an abundant amount 799:816 an abundant amount of L-Cys for the enrichment of glycopeptides 799:861 The ultrathin Au nanowires have a one-dimensional structure and were easily grafted with an abundant amount of L-Cys for the enrichment of glycopeptides. 28433058 2 56 theme surface 600:606 arg1 area 608:611 large surface area 594:611 large surface area of ultrathin Au nanowires 594:637 In this study, a novel ultrathin Au nanowire assisted zwitterionic hydrophilic magnetic graphene oxide (GO-Fe3O4/SiO2/AuNWs/L-Cys) was synthesized with the good biocompatibility of GO, strong magnetic responses of Fe3O4, large surface area of ultrathin Au nanowires and excellent hydrophilicity of L-Cys via four simple and rapid steps. 28433058 7 57 theme liver 1368:1372 arg1 proteins 1374:1381 mouse liver proteins 1362:1381 mouse liver proteins 1362:1381 A total of 793 glycopeptides from 467 glycoproteins were identified in three replicate analyses of 40 μg of mouse liver proteins. 28433058 7 58 from glycoproteins 1292:1304 arg1 total 1256:1260 A total 1254:1260 A total of 793 glycopeptides from 467 glycoproteins 1254:1304 A total of 793 glycopeptides from 467 glycoproteins were identified in three replicate analyses of 40 μg of mouse liver proteins. 28433058 7 58 from glycoproteins 1292:1304 arg1 glycopeptides 1269:1281 793 glycopeptides 1265:1281 793 glycopeptides from 467 glycoproteins 1265:1304 A total of 793 glycopeptides from 467 glycoproteins were identified in three replicate analyses of 40 μg of mouse liver proteins. 28433058 1 59 theme Protein 136:142 arg1 glycosylation 144:156 Protein glycosylation 136:156 Protein glycosylation 136:156 Protein glycosylation has been proven to participate in a variety of complex biological processes; however, the low abundance of glycopeptides in natural samples makes it essential to develop methods to isolate and enrich glycopeptides. 28433058 0 60 theme ZIC-HILIC 57:65 arg1 composites 67:76 assisted magnetic graphene-silica ZIC-HILIC composites 23:76 assisted magnetic graphene-silica ZIC-HILIC composites for highly specific enrichment of N-linked glycopeptides 23:133 Ultrathin Au nanowires assisted magnetic graphene-silica ZIC-HILIC composites for highly specific enrichment of N-linked glycopeptides. 28433058 4 61 gly glycopeptides 955:967 arg2 glycopeptides 955:967 26 glycopeptides 952:967 26 glycopeptides from a human IgG digest 952:991 After the GO-Fe3O4/SiO2/AuNWs/L-Cys composites were applied to glycopeptide enrichment, 26 glycopeptides from a human IgG digest could be identified, with a detection limit as low as 10 fmol. 28433058 4 61 gly glycopeptides 955:967 arg1 digest 986:991 a human IgG digest 974:991 a human IgG digest 974:991 After the GO-Fe3O4/SiO2/AuNWs/L-Cys composites were applied to glycopeptide enrichment, 26 glycopeptides from a human IgG digest could be identified, with a detection limit as low as 10 fmol. 28433058 1 62 from abundance 252:260 arg1 samples 290:296 natural samples 282:296 natural samples 282:296 Protein glycosylation has been proven to participate in a variety of complex biological processes; however, the low abundance of glycopeptides in natural samples makes it essential to develop methods to isolate and enrich glycopeptides. 28433058 7 63 theme proteins 1374:1381 arg1 40 μg 1353:1357 40 μg 1353:1357 40 μg of mouse liver proteins 1353:1381 A total of 793 glycopeptides from 467 glycoproteins were identified in three replicate analyses of 40 μg of mouse liver proteins. 28433058 7 64 theme glycopeptides 1269:1281 arg1 total 1256:1260 A total 1254:1260 A total of 793 glycopeptides from 467 glycoproteins 1254:1304 A total of 793 glycopeptides from 467 glycoproteins were identified in three replicate analyses of 40 μg of mouse liver proteins. 28433058 4 65 theme glycopeptide 927:938 arg1 enrichment 940:949 glycopeptide enrichment 927:949 glycopeptide enrichment 927:949 After the GO-Fe3O4/SiO2/AuNWs/L-Cys composites were applied to glycopeptide enrichment, 26 glycopeptides from a human IgG digest could be identified, with a detection limit as low as 10 fmol. 28433058 3 66 theme one-dimensional 744:758 arg1 structure 760:768 a one-dimensional structure 742:768 a one-dimensional structure 742:768 The ultrathin Au nanowires have a one-dimensional structure and were easily grafted with an abundant amount of L-Cys for the enrichment of glycopeptides. 28433058 8 67 theme glycoproteins 1489:1501 arg1 analysis 1477:1484 the analysis 1473:1484 the analysis of glycoproteins 1473:1501 The results demonstrated the great potential of GO-Fe3O4/SiO2/AuNWs/L-Cys composites for the analysis of glycoproteins. 28433058 7 68 theme 40 μg 1353:1357 arg1 analyses 1341:1348 three replicate analyses 1325:1348 three replicate analyses of 40 μg of mouse liver proteins 1325:1381 A total of 793 glycopeptides from 467 glycoproteins were identified in three replicate analyses of 40 μg of mouse liver proteins. 28433058 6 69 theme real 1229:1232 arg1 samples 1245:1251 real biological samples 1229:1251 real biological samples 1229:1251 Furthermore, the composites were applied for the analysis of real biological samples. 28433058 3 70 theme L-Cys 821:825 arg1 L-Cys 821:825 L-Cys 821:825 L-Cys 821:825 The ultrathin Au nanowires have a one-dimensional structure and were easily grafted with an abundant amount of L-Cys for the enrichment of glycopeptides. 28433058 3 70 theme L-Cys 821:825 arg1 amount 811:816 an abundant amount 799:816 an abundant amount of L-Cys for the enrichment of glycopeptides 799:861 The ultrathin Au nanowires have a one-dimensional structure and were easily grafted with an abundant amount of L-Cys for the enrichment of glycopeptides. 28433058 2 71 theme Fe3O4 587:591 arg1 responses 574:582 strong magnetic responses 558:582 strong magnetic responses of Fe3O4 558:591 In this study, a novel ultrathin Au nanowire assisted zwitterionic hydrophilic magnetic graphene oxide (GO-Fe3O4/SiO2/AuNWs/L-Cys) was synthesized with the good biocompatibility of GO, strong magnetic responses of Fe3O4, large surface area of ultrathin Au nanowires and excellent hydrophilicity of L-Cys via four simple and rapid steps. 28433058 2 71 theme Fe3O4 587:591 arg1 area 608:611 large surface area 594:611 large surface area of ultrathin Au nanowires 594:637 In this study, a novel ultrathin Au nanowire assisted zwitterionic hydrophilic magnetic graphene oxide (GO-Fe3O4/SiO2/AuNWs/L-Cys) was synthesized with the good biocompatibility of GO, strong magnetic responses of Fe3O4, large surface area of ultrathin Au nanowires and excellent hydrophilicity of L-Cys via four simple and rapid steps. 28433058 2 71 theme Fe3O4 587:591 arg1 biocompatibility 534:549 the good biocompatibility 525:549 the good biocompatibility of GO 525:555 In this study, a novel ultrathin Au nanowire assisted zwitterionic hydrophilic magnetic graphene oxide (GO-Fe3O4/SiO2/AuNWs/L-Cys) was synthesized with the good biocompatibility of GO, strong magnetic responses of Fe3O4, large surface area of ultrathin Au nanowires and excellent hydrophilicity of L-Cys via four simple and rapid steps. 28433058 2 71 theme Fe3O4 587:591 arg1 hydrophilicity 653:666 excellent hydrophilicity 643:666 excellent hydrophilicity of L-Cys 643:675 In this study, a novel ultrathin Au nanowire assisted zwitterionic hydrophilic magnetic graphene oxide (GO-Fe3O4/SiO2/AuNWs/L-Cys) was synthesized with the good biocompatibility of GO, strong magnetic responses of Fe3O4, large surface area of ultrathin Au nanowires and excellent hydrophilicity of L-Cys via four simple and rapid steps. 28433058 5 72 theme abundant 1067:1074 arg1 amount 1076:1081 the abundant amount 1063:1081 the abundant amount of grafted L-Cys 1063:1098 Due to the abundant amount of grafted L-Cys, the composites also showed a large binding capacity (150 μg mg-1). 28433058 5 72 theme abundant 1067:1074 arg1 L-Cys 1094:1098 grafted L-Cys 1086:1098 grafted L-Cys 1086:1098 Due to the abundant amount of grafted L-Cys, the composites also showed a large binding capacity (150 μg mg-1). 28433058 7 73 theme mouse 1362:1366 arg1 proteins 1374:1381 mouse liver proteins 1362:1381 mouse liver proteins 1362:1381 A total of 793 glycopeptides from 467 glycoproteins were identified in three replicate analyses of 40 μg of mouse liver proteins. 28433058 7 74 from total 1256:1260 arg1 glycoproteins 1292:1304 467 glycoproteins 1288:1304 467 glycoproteins 1288:1304 A total of 793 glycopeptides from 467 glycoproteins were identified in three replicate analyses of 40 μg of mouse liver proteins. 28433058 2 75 theme good 529:532 arg1 biocompatibility 534:549 the good biocompatibility 525:549 the good biocompatibility of GO 525:555 In this study, a novel ultrathin Au nanowire assisted zwitterionic hydrophilic magnetic graphene oxide (GO-Fe3O4/SiO2/AuNWs/L-Cys) was synthesized with the good biocompatibility of GO, strong magnetic responses of Fe3O4, large surface area of ultrathin Au nanowires and excellent hydrophilicity of L-Cys via four simple and rapid steps. 28433058 8 76 theme composites 1458:1467 arg1 potential 1419:1427 the great potential 1409:1427 the great potential of GO-Fe3O4/SiO2/AuNWs/L-Cys composites for the analysis of glycoproteins 1409:1501 The results demonstrated the great potential of GO-Fe3O4/SiO2/AuNWs/L-Cys composites for the analysis of glycoproteins. 28433058 2 77 theme zwitterionic 427:438 arg1 GO-Fe3O4/SiO2/AuNWs/L-Cys 477:501 assisted zwitterionic hydrophilic magnetic graphene oxide (GO-Fe3O4/SiO2/AuNWs/L-Cys) 418:502 a novel ultrathin Au nanowire assisted zwitterionic hydrophilic magnetic graphene oxide (GO-Fe3O4/SiO2/AuNWs/L-Cys) 388:502 In this study, a novel ultrathin Au nanowire assisted zwitterionic hydrophilic magnetic graphene oxide (GO-Fe3O4/SiO2/AuNWs/L-Cys) was synthesized with the good biocompatibility of GO, strong magnetic responses of Fe3O4, large surface area of ultrathin Au nanowires and excellent hydrophilicity of L-Cys via four simple and rapid steps. 28433058 4 78 gly glycopeptide 927:938 arg2 glycopeptide 927:938 glycopeptide enrichment 927:949 glycopeptide enrichment 927:949 After the GO-Fe3O4/SiO2/AuNWs/L-Cys composites were applied to glycopeptide enrichment, 26 glycopeptides from a human IgG digest could be identified, with a detection limit as low as 10 fmol. 28433058 1 79 theme low 248:250 arg1 abundance 252:260 the low abundance 244:260 the low abundance of glycopeptides in natural samples 244:296 Protein glycosylation has been proven to participate in a variety of complex biological processes; however, the low abundance of glycopeptides in natural samples makes it essential to develop methods to isolate and enrich glycopeptides. 28433058 3 80 theme ultrathin 714:722 arg1 nanowires 727:735 The ultrathin Au nanowires 710:735 The ultrathin Au nanowires 710:735 The ultrathin Au nanowires have a one-dimensional structure and were easily grafted with an abundant amount of L-Cys for the enrichment of glycopeptides. 28433058 6 81 theme samples 1245:1251 arg1 analysis 1217:1224 the analysis 1213:1224 the analysis of real biological samples 1213:1251 Furthermore, the composites were applied for the analysis of real biological samples. 28433058 0 82 link N-linked 112:119 arg1 glycopeptides 121:133 N-linked glycopeptides 112:133 N-linked glycopeptides 112:133 Ultrathin Au nanowires assisted magnetic graphene-silica ZIC-HILIC composites for highly specific enrichment of N-linked glycopeptides. 28433058 4 83 theme IgG 982:984 arg1 digest 986:991 a human IgG digest 974:991 a human IgG digest 974:991 After the GO-Fe3O4/SiO2/AuNWs/L-Cys composites were applied to glycopeptide enrichment, 26 glycopeptides from a human IgG digest could be identified, with a detection limit as low as 10 fmol. 28360190 6 0 dep BPH 839:841 arg1 n=122 844:848 n=122 844:848 BPH; n=122 839:848 Diagnostic value was assessed between benign prostate hyperplasia (BPH; n=122) and patients with PCa (n=85). 28360190 11 1 theme PSA 1483:1485 arg1 ratio 1498:1502 The urinary vesicle-associated PSA extraction ratio 1452:1502 The urinary vesicle-associated PSA extraction ratio 1452:1502 CONCLUSIONS The urinary vesicle-associated PSA extraction ratio is increased in PCa which is a direct result of the abundant presence of extracellular vesicles in urine of patients with PCa. 28360190 10 2 theme vesicle-associated 1298:1315 arg1 ratio 1332:1336 vesicle-associated PSA extraction ratio 1298:1336 vesicle-associated PSA extraction ratio 1298:1336 Finally, vesicle-associated PSA extraction ratio proved beneficial in PCa diagnosis, next to serum PSA and the urinary glycosylation marker (p=0.021). 28360190 5 3 theme vesicle-associated 733:750 arg1 extractability 756:769 urinary vesicle-associated PSA extractability 725:769 urinary vesicle-associated PSA extractability 725:769 Urinary extracellular vesicles extraction by means of n-butanol allowed determination of urinary vesicle-associated PSA extractability. 28360190 2 4 theme significant 264:274 arg1 role 276:279 a significant role 262:279 a significant role 262:279 Asparagine (N)-linked glycosylation could play a significant role in the pathological mechanism of these vesicles. 28360190 8 5 theme patients 1068:1075 arg1 urine 1059:1063 urine 1059:1063 urine of patients with PCa versus patients with BPH resulting in a higher vesicle-associated PSA extraction ratio (p<0.001) 1059:1181 RESULTS Urinary extracellular vesicles with a diameter of approximately 100 nm were more abundantly present in urine of patients with PCa versus patients with BPH resulting in a higher vesicle-associated PSA extraction ratio (p<0.001). 28360190 10 6 from beneficial 1345:1354 arg1 diagnosis 1363:1371 PCa diagnosis 1359:1371 PCa diagnosis 1359:1371 Finally, vesicle-associated PSA extraction ratio proved beneficial in PCa diagnosis, next to serum PSA and the urinary glycosylation marker (p=0.021). 28360190 6 7 with hyperplasia 826:836 arg1 n=85 874:877 n=85 874:877 n=85 874:877 Diagnostic value was assessed between benign prostate hyperplasia (BPH; n=122) and patients with PCa (n=85). 28360190 6 7 with hyperplasia 826:836 arg1 PCa 869:871 PCa 869:871 PCa (n=85) 869:878 Diagnostic value was assessed between benign prostate hyperplasia (BPH; n=122) and patients with PCa (n=85). 28360190 7 8 theme urine 912:916 arg1 N-glycosylation 918:932 urine N-glycosylation 912:932 urine N-glycosylation 912:932 Additionally, correlation with urine N-glycosylation was assessed. 28360190 13 9 theme biomarker 1935:1943 arg1 value 1921:1925 the prognostic value 1906:1925 the prognostic value of this biomarker 1906:1943 Further research is warranted to unravel the pathological link between N-glycosylation and extracellular vesicles in cancer, as well as to assess the prognostic value of this biomarker. 28360190 8 10 dep RESULTS 948:954 arg1 vesicles 978:985 Urinary extracellular vesicles 956:985 RESULTS Urinary extracellular vesicles with a diameter of approximately 100 nm 948:1025 RESULTS Urinary extracellular vesicles with a diameter of approximately 100 nm were more abundantly present in urine of patients with PCa versus patients with BPH resulting in a higher vesicle-associated PSA extraction ratio (p<0.001). 28360190 2 11 theme pathological 288:299 arg1 mechanism 301:309 the pathological mechanism 284:309 the pathological mechanism of these vesicles 284:327 Asparagine (N)-linked glycosylation could play a significant role in the pathological mechanism of these vesicles. 28360190 1 12 theme cancer 192:197 arg1 research 205:212 prostate cancer (PCa) research 183:212 prostate cancer (PCa) research 183:212 AIM Nowadays, extracellular vesicles are of great interest in prostate cancer (PCa) research. 28360190 8 13 theme patients 1093:1100 arg1 urine 1059:1063 urine 1059:1063 urine of patients with PCa versus patients with BPH resulting in a higher vesicle-associated PSA extraction ratio (p<0.001) 1059:1181 RESULTS Urinary extracellular vesicles with a diameter of approximately 100 nm were more abundantly present in urine of patients with PCa versus patients with BPH resulting in a higher vesicle-associated PSA extraction ratio (p<0.001). 28360190 6 14 theme Diagnostic 772:781 arg1 value 783:787 Diagnostic value 772:787 Diagnostic value 772:787 Diagnostic value was assessed between benign prostate hyperplasia (BPH; n=122) and patients with PCa (n=85). 28360190 11 15 theme urinary 1456:1462 arg1 ratio 1498:1502 The urinary vesicle-associated PSA extraction ratio 1452:1502 The urinary vesicle-associated PSA extraction ratio 1452:1502 CONCLUSIONS The urinary vesicle-associated PSA extraction ratio is increased in PCa which is a direct result of the abundant presence of extracellular vesicles in urine of patients with PCa. 28360190 5 16 theme extractability 756:769 arg1 determination 708:720 determination 708:720 determination of urinary vesicle-associated PSA extractability 708:769 Urinary extracellular vesicles extraction by means of n-butanol allowed determination of urinary vesicle-associated PSA extractability. 28360190 1 17 theme Nowadays 125:132 arg1 vesicles 149:156 Nowadays, extracellular vesicles 125:156 vesicles 149:156 AIM Nowadays, extracellular vesicles are of great interest in prostate cancer (PCa) research. 28360190 11 18 theme vesicles 1591:1598 arg1 presence 1565:1572 the abundant presence 1552:1572 the abundant presence of extracellular vesicles in urine of patients with PCa 1552:1628 CONCLUSIONS The urinary vesicle-associated PSA extraction ratio is increased in PCa which is a direct result of the abundant presence of extracellular vesicles in urine of patients with PCa. 28360190 1 19 theme extracellular 135:147 arg1 vesicles 149:156 Nowadays, extracellular vesicles 125:156 vesicles 149:156 AIM Nowadays, extracellular vesicles are of great interest in prostate cancer (PCa) research. 28360190 12 20 theme urinary 1635:1641 arg1 ratio 1677:1681 The urinary vesicle-associated PSA extraction ratio 1631:1681 The urinary vesicle-associated PSA extraction ratio 1631:1681 The urinary vesicle-associated PSA extraction ratio was associated with changes in N-glycoforms and showed diagnostic potential. 28360190 10 21 theme extraction 1321:1330 arg1 ratio 1332:1336 vesicle-associated PSA extraction ratio 1298:1336 vesicle-associated PSA extraction ratio 1298:1336 Finally, vesicle-associated PSA extraction ratio proved beneficial in PCa diagnosis, next to serum PSA and the urinary glycosylation marker (p=0.021). 28360190 1 22 from interest 171:178 arg1 research 205:212 prostate cancer (PCa) research 183:212 prostate cancer (PCa) research 183:212 AIM Nowadays, extracellular vesicles are of great interest in prostate cancer (PCa) research. 28360190 12 23 theme PSA 1662:1664 arg1 ratio 1677:1681 The urinary vesicle-associated PSA extraction ratio 1631:1681 The urinary vesicle-associated PSA extraction ratio 1631:1681 The urinary vesicle-associated PSA extraction ratio was associated with changes in N-glycoforms and showed diagnostic potential. 28360190 11 24 theme patients 1612:1619 arg1 urine 1603:1607 urine 1603:1607 urine of patients with PCa 1603:1628 CONCLUSIONS The urinary vesicle-associated PSA extraction ratio is increased in PCa which is a direct result of the abundant presence of extracellular vesicles in urine of patients with PCa. 28360190 2 25 link -linked 229:235 arg1 glycosylation 237:249 Asparagine (N)-linked glycosylation 215:249 Asparagine (N)-linked glycosylation 215:249 Asparagine (N)-linked glycosylation could play a significant role in the pathological mechanism of these vesicles. 28360190 5 26 theme extracellular 644:656 arg1 extraction 667:676 Urinary extracellular vesicles extraction 636:676 Urinary extracellular vesicles extraction by means of n-butanol 636:698 Urinary extracellular vesicles extraction by means of n-butanol allowed determination of urinary vesicle-associated PSA extractability. 28360190 1 27 theme great 165:169 arg1 interest 171:178 great interest 165:178 great interest 165:178 AIM Nowadays, extracellular vesicles are of great interest in prostate cancer (PCa) research. 28360190 0 28 from Release 0:6 arg1 cancer 54:59 prostate cancer 45:59 prostate cancer 45:59 Release of urinary extracellular vesicles in prostate cancer is associated with altered urinary N-glycosylation profile. 28360190 0 29 theme urinary 88:94 arg1 profile 112:118 altered urinary N-glycosylation profile 80:118 altered urinary N-glycosylation profile 80:118 Release of urinary extracellular vesicles in prostate cancer is associated with altered urinary N-glycosylation profile. 28360190 11 30 from urine 1603:1607 arg1 result 1542:1547 a direct result 1533:1547 a direct result of the abundant presence of extracellular vesicles in urine of patients with PCa 1533:1628 CONCLUSIONS The urinary vesicle-associated PSA extraction ratio is increased in PCa which is a direct result of the abundant presence of extracellular vesicles in urine of patients with PCa. 28360190 11 30 from urine 1603:1607 arg1 PCa 1520:1522 PCa 1520:1522 PCa which is a direct result of the abundant presence of extracellular vesicles in urine of patients with PCa 1520:1628 CONCLUSIONS The urinary vesicle-associated PSA extraction ratio is increased in PCa which is a direct result of the abundant presence of extracellular vesicles in urine of patients with PCa. 28360190 1 31 dep AIM 121:123 arg1 vesicles 149:156 Nowadays, extracellular vesicles 125:156 vesicles 149:156 AIM Nowadays, extracellular vesicles are of great interest in prostate cancer (PCa) research. 28360190 10 32 theme serum 1382:1386 arg1 PSA 1388:1390 serum PSA 1382:1390 serum PSA 1382:1390 Finally, vesicle-associated PSA extraction ratio proved beneficial in PCa diagnosis, next to serum PSA and the urinary glycosylation marker (p=0.021). 28360190 8 33 theme higher 1126:1131 arg1 p<0.001 1174:1180 p<0.001 1174:1180 p<0.001 1174:1180 RESULTS Urinary extracellular vesicles with a diameter of approximately 100 nm were more abundantly present in urine of patients with PCa versus patients with BPH resulting in a higher vesicle-associated PSA extraction ratio (p<0.001). 28360190 8 33 theme higher 1126:1131 arg1 ratio 1167:1171 a higher vesicle-associated PSA extraction ratio 1124:1171 a higher vesicle-associated PSA extraction ratio (p<0.001) 1124:1181 RESULTS Urinary extracellular vesicles with a diameter of approximately 100 nm were more abundantly present in urine of patients with PCa versus patients with BPH resulting in a higher vesicle-associated PSA extraction ratio (p<0.001). 28360190 8 34 theme extracellular 964:976 arg1 vesicles 978:985 Urinary extracellular vesicles 956:985 RESULTS Urinary extracellular vesicles with a diameter of approximately 100 nm 948:1025 RESULTS Urinary extracellular vesicles with a diameter of approximately 100 nm were more abundantly present in urine of patients with PCa versus patients with BPH resulting in a higher vesicle-associated PSA extraction ratio (p<0.001). 28360190 11 35 attach presence 1565:1572 arg1 urine 1603:1607 urine 1603:1607 urine of patients with PCa 1603:1628 CONCLUSIONS The urinary vesicle-associated PSA extraction ratio is increased in PCa which is a direct result of the abundant presence of extracellular vesicles in urine of patients with PCa. 28360190 11 35 attach presence 1565:1572 arg2 vesicles 1591:1598 extracellular vesicles 1577:1598 extracellular vesicles 1577:1598 CONCLUSIONS The urinary vesicle-associated PSA extraction ratio is increased in PCa which is a direct result of the abundant presence of extracellular vesicles in urine of patients with PCa. 28360190 3 36 theme prostate-specific 435:451 arg1 PSA 462:464 PSA 462:464 PSA 462:464 We investigated if prostatic protein N-glycosylation profiles were related to urinary vesicle-associated prostate-specific antigen (PSA) extractability and if this parameter showed diagnostic potential for PCa. 28360190 3 36 theme prostate-specific 435:451 arg1 antigen 453:459 vesicle-associated prostate-specific antigen 416:459 urinary vesicle-associated prostate-specific antigen (PSA) extractability 408:480 We investigated if prostatic protein N-glycosylation profiles were related to urinary vesicle-associated prostate-specific antigen (PSA) extractability and if this parameter showed diagnostic potential for PCa. 28360190 8 37 theme PSA 1152:1154 arg1 p<0.001 1174:1180 p<0.001 1174:1180 p<0.001 1174:1180 RESULTS Urinary extracellular vesicles with a diameter of approximately 100 nm were more abundantly present in urine of patients with PCa versus patients with BPH resulting in a higher vesicle-associated PSA extraction ratio (p<0.001). 28360190 8 37 theme PSA 1152:1154 arg1 ratio 1167:1171 a higher vesicle-associated PSA extraction ratio 1124:1171 a higher vesicle-associated PSA extraction ratio (p<0.001) 1124:1181 RESULTS Urinary extracellular vesicles with a diameter of approximately 100 nm were more abundantly present in urine of patients with PCa versus patients with BPH resulting in a higher vesicle-associated PSA extraction ratio (p<0.001). 28360190 12 38 theme diagnostic 1738:1747 arg1 potential 1749:1757 diagnostic potential 1738:1757 diagnostic potential 1738:1757 The urinary vesicle-associated PSA extraction ratio was associated with changes in N-glycoforms and showed diagnostic potential. 28360190 3 39 theme protein 359:365 arg1 profiles 383:390 prostatic protein N-glycosylation profiles 349:390 prostatic protein N-glycosylation profiles 349:390 We investigated if prostatic protein N-glycosylation profiles were related to urinary vesicle-associated prostate-specific antigen (PSA) extractability and if this parameter showed diagnostic potential for PCa. 28360190 13 40 theme Further 1760:1766 arg1 research 1768:1775 Further research 1760:1775 Further research 1760:1775 Further research is warranted to unravel the pathological link between N-glycosylation and extracellular vesicles in cancer, as well as to assess the prognostic value of this biomarker. 28360190 10 41 theme urinary 1400:1406 arg1 p=0.021 1430:1436 p=0.021 1430:1436 p=0.021 1430:1436 Finally, vesicle-associated PSA extraction ratio proved beneficial in PCa diagnosis, next to serum PSA and the urinary glycosylation marker (p=0.021). 28360190 10 41 theme urinary 1400:1406 arg1 marker 1422:1427 the urinary glycosylation marker 1396:1427 the urinary glycosylation marker (p=0.021) 1396:1437 Finally, vesicle-associated PSA extraction ratio proved beneficial in PCa diagnosis, next to serum PSA and the urinary glycosylation marker (p=0.021). 28360190 0 42 theme urinary 11:17 arg1 vesicles 33:40 urinary extracellular vesicles 11:40 urinary extracellular vesicles 11:40 Release of urinary extracellular vesicles in prostate cancer is associated with altered urinary N-glycosylation profile. 28360190 8 43 from present 1048:1054 arg1 urine 1059:1063 urine 1059:1063 urine of patients with PCa versus patients with BPH resulting in a higher vesicle-associated PSA extraction ratio (p<0.001) 1059:1181 RESULTS Urinary extracellular vesicles with a diameter of approximately 100 nm were more abundantly present in urine of patients with PCa versus patients with BPH resulting in a higher vesicle-associated PSA extraction ratio (p<0.001). 28360190 3 44 theme urinary 408:414 arg1 extractability 467:480 urinary vesicle-associated prostate-specific antigen (PSA) extractability 408:480 urinary vesicle-associated prostate-specific antigen (PSA) extractability 408:480 We investigated if prostatic protein N-glycosylation profiles were related to urinary vesicle-associated prostate-specific antigen (PSA) extractability and if this parameter showed diagnostic potential for PCa. 28360190 9 45 theme vesicle-associated 1190:1207 arg1 ratio 1224:1228 vesicle-associated PSA extraction ratio 1190:1228 vesicle-associated PSA extraction ratio 1190:1228 Next, vesicle-associated PSA extraction ratio was correlated to biantennary core-fucosylation (p=0.003). 28360190 0 46 theme vesicles 33:40 arg1 Release 0:6 Release 0:6 Release of urinary extracellular vesicles in prostate cancer 0:59 Release of urinary extracellular vesicles in prostate cancer is associated with altered urinary N-glycosylation profile. 28360190 13 47 from N-glycosylation 1831:1845 arg1 cancer 1877:1882 cancer 1877:1882 cancer 1877:1882 Further research is warranted to unravel the pathological link between N-glycosylation and extracellular vesicles in cancer, as well as to assess the prognostic value of this biomarker. 28360190 12 48 from changes 1703:1709 arg1 N-glycoforms 1714:1725 N-glycoforms 1714:1725 N-glycoforms 1714:1725 The urinary vesicle-associated PSA extraction ratio was associated with changes in N-glycoforms and showed diagnostic potential. 28360190 7 49 with correlation 895:905 arg1 N-glycosylation 918:932 urine N-glycosylation 912:932 urine N-glycosylation 912:932 Additionally, correlation with urine N-glycosylation was assessed. 28360190 13 50 theme prognostic 1910:1919 arg1 value 1921:1925 the prognostic value 1906:1925 the prognostic value of this biomarker 1906:1943 Further research is warranted to unravel the pathological link between N-glycosylation and extracellular vesicles in cancer, as well as to assess the prognostic value of this biomarker. 28360190 9 51 theme extraction 1213:1222 arg1 ratio 1224:1228 vesicle-associated PSA extraction ratio 1190:1228 vesicle-associated PSA extraction ratio 1190:1228 Next, vesicle-associated PSA extraction ratio was correlated to biantennary core-fucosylation (p=0.003). 28360190 0 52 theme prostate 45:52 arg1 cancer 54:59 prostate cancer 45:59 prostate cancer 45:59 Release of urinary extracellular vesicles in prostate cancer is associated with altered urinary N-glycosylation profile. 28360190 4 53 theme extracellular 557:569 arg1 vesicles 571:578 Urinary extracellular vesicles 549:578 METHODS Urinary extracellular vesicles 541:578 METHODS Urinary extracellular vesicles were visualised using transmission electron microscopy. 28360190 8 54 from urine 1059:1063 arg1 present 1048:1054 present 1048:1054 present 1048:1054 RESULTS Urinary extracellular vesicles with a diameter of approximately 100 nm were more abundantly present in urine of patients with PCa versus patients with BPH resulting in a higher vesicle-associated PSA extraction ratio (p<0.001). 28360190 11 55 theme extraction 1487:1496 arg1 ratio 1498:1502 The urinary vesicle-associated PSA extraction ratio 1452:1502 The urinary vesicle-associated PSA extraction ratio 1452:1502 CONCLUSIONS The urinary vesicle-associated PSA extraction ratio is increased in PCa which is a direct result of the abundant presence of extracellular vesicles in urine of patients with PCa. 28360190 11 56 theme vesicle-associated 1464:1481 arg1 ratio 1498:1502 The urinary vesicle-associated PSA extraction ratio 1452:1502 The urinary vesicle-associated PSA extraction ratio 1452:1502 CONCLUSIONS The urinary vesicle-associated PSA extraction ratio is increased in PCa which is a direct result of the abundant presence of extracellular vesicles in urine of patients with PCa. 28360190 6 57 theme benign 810:815 arg1 hyperplasia 826:836 benign prostate hyperplasia 810:836 benign prostate hyperplasia (BPH; n=122) 810:849 Diagnostic value was assessed between benign prostate hyperplasia (BPH; n=122) and patients with PCa (n=85). 28360190 6 57 theme benign 810:815 arg1 BPH 839:841 BPH 839:841 BPH; n=122 839:848 Diagnostic value was assessed between benign prostate hyperplasia (BPH; n=122) and patients with PCa (n=85). 28360190 10 58 theme PSA 1317:1319 arg1 ratio 1332:1336 vesicle-associated PSA extraction ratio 1298:1336 vesicle-associated PSA extraction ratio 1298:1336 Finally, vesicle-associated PSA extraction ratio proved beneficial in PCa diagnosis, next to serum PSA and the urinary glycosylation marker (p=0.021). 28360190 4 59 theme electron 615:622 arg1 microscopy 624:633 transmission electron microscopy 602:633 transmission electron microscopy 602:633 METHODS Urinary extracellular vesicles were visualised using transmission electron microscopy. 28360190 5 60 theme urinary 725:731 arg1 extractability 756:769 urinary vesicle-associated PSA extractability 725:769 urinary vesicle-associated PSA extractability 725:769 Urinary extracellular vesicles extraction by means of n-butanol allowed determination of urinary vesicle-associated PSA extractability. 28360190 11 61 theme abundant 1556:1563 arg1 presence 1565:1572 the abundant presence 1552:1572 the abundant presence of extracellular vesicles in urine of patients with PCa 1552:1628 CONCLUSIONS The urinary vesicle-associated PSA extraction ratio is increased in PCa which is a direct result of the abundant presence of extracellular vesicles in urine of patients with PCa. 28360190 11 62 dep CONCLUSIONS 1440:1450 arg1 increased 1507:1515 increased 1507:1515 is increased in PCa which is a direct result of the abundant presence of extracellular vesicles in urine of patients with PCa 1504:1628 CONCLUSIONS The urinary vesicle-associated PSA extraction ratio is increased in PCa which is a direct result of the abundant presence of extracellular vesicles in urine of patients with PCa. 28360190 1 63 theme prostate 183:190 arg1 PCa 200:202 PCa 200:202 PCa 200:202 AIM Nowadays, extracellular vesicles are of great interest in prostate cancer (PCa) research. 28360190 1 63 theme prostate 183:190 arg1 cancer 192:197 prostate cancer 183:197 prostate cancer (PCa) research 183:212 AIM Nowadays, extracellular vesicles are of great interest in prostate cancer (PCa) research. 28360190 8 64 with vesicles 978:985 arg1 diameter 994:1001 a diameter 992:1001 a diameter of approximately 100 nm 992:1025 RESULTS Urinary extracellular vesicles with a diameter of approximately 100 nm were more abundantly present in urine of patients with PCa versus patients with BPH resulting in a higher vesicle-associated PSA extraction ratio (p<0.001). 28360190 10 65 from diagnosis 1363:1371 arg1 beneficial 1345:1354 beneficial 1345:1354 beneficial 1345:1354 Finally, vesicle-associated PSA extraction ratio proved beneficial in PCa diagnosis, next to serum PSA and the urinary glycosylation marker (p=0.021). 28360190 6 66 with patients 855:862 arg1 n=85 874:877 n=85 874:877 n=85 874:877 Diagnostic value was assessed between benign prostate hyperplasia (BPH; n=122) and patients with PCa (n=85). 28360190 6 66 with patients 855:862 arg1 PCa 869:871 PCa 869:871 PCa (n=85) 869:878 Diagnostic value was assessed between benign prostate hyperplasia (BPH; n=122) and patients with PCa (n=85). 28360190 2 67 theme vesicles 320:327 arg1 mechanism 301:309 the pathological mechanism 284:309 the pathological mechanism of these vesicles 284:327 Asparagine (N)-linked glycosylation could play a significant role in the pathological mechanism of these vesicles. 28360190 5 68 theme PSA 752:754 arg1 extractability 756:769 urinary vesicle-associated PSA extractability 725:769 urinary vesicle-associated PSA extractability 725:769 Urinary extracellular vesicles extraction by means of n-butanol allowed determination of urinary vesicle-associated PSA extractability. 28360190 11 69 with patients 1612:1619 arg1 PCa 1626:1628 PCa 1626:1628 PCa 1626:1628 CONCLUSIONS The urinary vesicle-associated PSA extraction ratio is increased in PCa which is a direct result of the abundant presence of extracellular vesicles in urine of patients with PCa. 28360190 8 70 attach present 1048:1054 arg1 urine 1059:1063 urine 1059:1063 urine of patients with PCa versus patients with BPH resulting in a higher vesicle-associated PSA extraction ratio (p<0.001) 1059:1181 RESULTS Urinary extracellular vesicles with a diameter of approximately 100 nm were more abundantly present in urine of patients with PCa versus patients with BPH resulting in a higher vesicle-associated PSA extraction ratio (p<0.001). 28360190 8 70 attach present 1048:1054 arg2 RESULTS 948:954 RESULTS 948:954 RESULTS Urinary extracellular vesicles with a diameter of approximately 100 nm 948:1025 RESULTS Urinary extracellular vesicles with a diameter of approximately 100 nm were more abundantly present in urine of patients with PCa versus patients with BPH resulting in a higher vesicle-associated PSA extraction ratio (p<0.001). 28360190 11 71 theme extracellular 1577:1589 arg1 vesicles 1591:1598 extracellular vesicles 1577:1598 extracellular vesicles 1577:1598 CONCLUSIONS The urinary vesicle-associated PSA extraction ratio is increased in PCa which is a direct result of the abundant presence of extracellular vesicles in urine of patients with PCa. 28360190 13 72 from vesicles 1865:1872 arg1 cancer 1877:1882 cancer 1877:1882 cancer 1877:1882 Further research is warranted to unravel the pathological link between N-glycosylation and extracellular vesicles in cancer, as well as to assess the prognostic value of this biomarker. 28360190 12 73 theme vesicle-associated 1643:1660 arg1 ratio 1677:1681 The urinary vesicle-associated PSA extraction ratio 1631:1681 The urinary vesicle-associated PSA extraction ratio 1631:1681 The urinary vesicle-associated PSA extraction ratio was associated with changes in N-glycoforms and showed diagnostic potential. 28360190 11 74 theme presence 1565:1572 arg1 result 1542:1547 a direct result 1533:1547 a direct result of the abundant presence of extracellular vesicles in urine of patients with PCa 1533:1628 CONCLUSIONS The urinary vesicle-associated PSA extraction ratio is increased in PCa which is a direct result of the abundant presence of extracellular vesicles in urine of patients with PCa. 28360190 11 74 theme presence 1565:1572 arg1 PCa 1520:1522 PCa 1520:1522 PCa which is a direct result of the abundant presence of extracellular vesicles in urine of patients with PCa 1520:1628 CONCLUSIONS The urinary vesicle-associated PSA extraction ratio is increased in PCa which is a direct result of the abundant presence of extracellular vesicles in urine of patients with PCa. 28360190 2 75 theme -linked 229:235 arg1 glycosylation 237:249 Asparagine (N)-linked glycosylation 215:249 Asparagine (N)-linked glycosylation 215:249 Asparagine (N)-linked glycosylation could play a significant role in the pathological mechanism of these vesicles. 28360190 13 76 gly N-glycosylation 1831:1845 arg1 cancer 1877:1882 cancer 1877:1882 cancer 1877:1882 Further research is warranted to unravel the pathological link between N-glycosylation and extracellular vesicles in cancer, as well as to assess the prognostic value of this biomarker. 28360190 12 77 theme extraction 1666:1675 arg1 ratio 1677:1681 The urinary vesicle-associated PSA extraction ratio 1631:1681 The urinary vesicle-associated PSA extraction ratio 1631:1681 The urinary vesicle-associated PSA extraction ratio was associated with changes in N-glycoforms and showed diagnostic potential. 28360190 8 78 with patients 1068:1075 arg1 PCa 1082:1084 PCa 1082:1084 PCa 1082:1084 RESULTS Urinary extracellular vesicles with a diameter of approximately 100 nm were more abundantly present in urine of patients with PCa versus patients with BPH resulting in a higher vesicle-associated PSA extraction ratio (p<0.001). 28360190 3 79 theme prostatic 349:357 arg1 profiles 383:390 prostatic protein N-glycosylation profiles 349:390 prostatic protein N-glycosylation profiles 349:390 We investigated if prostatic protein N-glycosylation profiles were related to urinary vesicle-associated prostate-specific antigen (PSA) extractability and if this parameter showed diagnostic potential for PCa. 28360190 0 80 theme altered 80:86 arg1 profile 112:118 altered urinary N-glycosylation profile 80:118 altered urinary N-glycosylation profile 80:118 Release of urinary extracellular vesicles in prostate cancer is associated with altered urinary N-glycosylation profile. 28360190 10 81 theme PCa 1359:1361 arg1 diagnosis 1363:1371 PCa diagnosis 1359:1371 PCa diagnosis 1359:1371 Finally, vesicle-associated PSA extraction ratio proved beneficial in PCa diagnosis, next to serum PSA and the urinary glycosylation marker (p=0.021). 28360190 0 82 theme N-glycosylation 96:110 arg1 profile 112:118 altered urinary N-glycosylation profile 80:118 altered urinary N-glycosylation profile 80:118 Release of urinary extracellular vesicles in prostate cancer is associated with altered urinary N-glycosylation profile. 28360190 4 83 dep METHODS 541:547 arg1 vesicles 571:578 Urinary extracellular vesicles 549:578 METHODS Urinary extracellular vesicles 541:578 METHODS Urinary extracellular vesicles were visualised using transmission electron microscopy. 28360190 5 84 theme vesicles 658:665 arg1 extraction 667:676 Urinary extracellular vesicles extraction 636:676 Urinary extracellular vesicles extraction by means of n-butanol 636:698 Urinary extracellular vesicles extraction by means of n-butanol allowed determination of urinary vesicle-associated PSA extractability. 28360190 8 85 with patients 1093:1100 arg1 BPH 1107:1109 BPH 1107:1109 BPH resulting in a higher vesicle-associated PSA extraction ratio (p<0.001) 1107:1181 RESULTS Urinary extracellular vesicles with a diameter of approximately 100 nm were more abundantly present in urine of patients with PCa versus patients with BPH resulting in a higher vesicle-associated PSA extraction ratio (p<0.001). 28360190 8 86 theme vesicle-associated 1133:1150 arg1 p<0.001 1174:1180 p<0.001 1174:1180 p<0.001 1174:1180 RESULTS Urinary extracellular vesicles with a diameter of approximately 100 nm were more abundantly present in urine of patients with PCa versus patients with BPH resulting in a higher vesicle-associated PSA extraction ratio (p<0.001). 28360190 8 86 theme vesicle-associated 1133:1150 arg1 ratio 1167:1171 a higher vesicle-associated PSA extraction ratio 1124:1171 a higher vesicle-associated PSA extraction ratio (p<0.001) 1124:1181 RESULTS Urinary extracellular vesicles with a diameter of approximately 100 nm were more abundantly present in urine of patients with PCa versus patients with BPH resulting in a higher vesicle-associated PSA extraction ratio (p<0.001). 28360190 7 87 gly N-glycosylation 918:932 arg1 correlation 895:905 correlation 895:905 correlation with urine N-glycosylation 895:932 Additionally, correlation with urine N-glycosylation was assessed. 28360190 13 88 theme extracellular 1851:1863 arg1 vesicles 1865:1872 extracellular vesicles 1851:1872 extracellular vesicles 1851:1872 Further research is warranted to unravel the pathological link between N-glycosylation and extracellular vesicles in cancer, as well as to assess the prognostic value of this biomarker. 28360190 8 89 theme extraction 1156:1165 arg1 p<0.001 1174:1180 p<0.001 1174:1180 p<0.001 1174:1180 RESULTS Urinary extracellular vesicles with a diameter of approximately 100 nm were more abundantly present in urine of patients with PCa versus patients with BPH resulting in a higher vesicle-associated PSA extraction ratio (p<0.001). 28360190 8 89 theme extraction 1156:1165 arg1 ratio 1167:1171 a higher vesicle-associated PSA extraction ratio 1124:1171 a higher vesicle-associated PSA extraction ratio (p<0.001) 1124:1181 RESULTS Urinary extracellular vesicles with a diameter of approximately 100 nm were more abundantly present in urine of patients with PCa versus patients with BPH resulting in a higher vesicle-associated PSA extraction ratio (p<0.001). 28360190 11 90 from presence 1565:1572 arg1 urine 1603:1607 urine 1603:1607 urine of patients with PCa 1603:1628 CONCLUSIONS The urinary vesicle-associated PSA extraction ratio is increased in PCa which is a direct result of the abundant presence of extracellular vesicles in urine of patients with PCa. 28360190 8 91 theme Urinary 956:962 arg1 vesicles 978:985 Urinary extracellular vesicles 956:985 RESULTS Urinary extracellular vesicles with a diameter of approximately 100 nm 948:1025 RESULTS Urinary extracellular vesicles with a diameter of approximately 100 nm were more abundantly present in urine of patients with PCa versus patients with BPH resulting in a higher vesicle-associated PSA extraction ratio (p<0.001). 28360190 13 92 theme pathological 1805:1816 arg1 link 1818:1821 the pathological link 1801:1821 the pathological link between N-glycosylation and extracellular vesicles in cancer 1801:1882 Further research is warranted to unravel the pathological link between N-glycosylation and extracellular vesicles in cancer, as well as to assess the prognostic value of this biomarker. 28360190 10 93 theme glycosylation 1408:1420 arg1 p=0.021 1430:1436 p=0.021 1430:1436 p=0.021 1430:1436 Finally, vesicle-associated PSA extraction ratio proved beneficial in PCa diagnosis, next to serum PSA and the urinary glycosylation marker (p=0.021). 28360190 10 93 theme glycosylation 1408:1420 arg1 marker 1422:1427 the urinary glycosylation marker 1396:1427 the urinary glycosylation marker (p=0.021) 1396:1437 Finally, vesicle-associated PSA extraction ratio proved beneficial in PCa diagnosis, next to serum PSA and the urinary glycosylation marker (p=0.021). 28360190 3 94 theme antigen 453:459 arg1 extractability 467:480 urinary vesicle-associated prostate-specific antigen (PSA) extractability 408:480 urinary vesicle-associated prostate-specific antigen (PSA) extractability 408:480 We investigated if prostatic protein N-glycosylation profiles were related to urinary vesicle-associated prostate-specific antigen (PSA) extractability and if this parameter showed diagnostic potential for PCa. 28360190 0 95 theme extracellular 19:31 arg1 vesicles 33:40 urinary extracellular vesicles 11:40 urinary extracellular vesicles 11:40 Release of urinary extracellular vesicles in prostate cancer is associated with altered urinary N-glycosylation profile. 28360190 5 96 theme Urinary 636:642 arg1 extraction 667:676 Urinary extracellular vesicles extraction 636:676 Urinary extracellular vesicles extraction by means of n-butanol 636:698 Urinary extracellular vesicles extraction by means of n-butanol allowed determination of urinary vesicle-associated PSA extractability. 28360190 3 97 theme N-glycosylation 367:381 arg1 profiles 383:390 prostatic protein N-glycosylation profiles 349:390 prostatic protein N-glycosylation profiles 349:390 We investigated if prostatic protein N-glycosylation profiles were related to urinary vesicle-associated prostate-specific antigen (PSA) extractability and if this parameter showed diagnostic potential for PCa. 28360190 4 98 theme transmission 602:613 arg1 microscopy 624:633 transmission electron microscopy 602:633 transmission electron microscopy 602:633 METHODS Urinary extracellular vesicles were visualised using transmission electron microscopy. 28360190 11 99 theme direct 1535:1540 arg1 result 1542:1547 a direct result 1533:1547 a direct result of the abundant presence of extracellular vesicles in urine of patients with PCa 1533:1628 CONCLUSIONS The urinary vesicle-associated PSA extraction ratio is increased in PCa which is a direct result of the abundant presence of extracellular vesicles in urine of patients with PCa. 28360190 11 99 theme direct 1535:1540 arg1 PCa 1520:1522 PCa 1520:1522 PCa which is a direct result of the abundant presence of extracellular vesicles in urine of patients with PCa 1520:1628 CONCLUSIONS The urinary vesicle-associated PSA extraction ratio is increased in PCa which is a direct result of the abundant presence of extracellular vesicles in urine of patients with PCa. 28360190 11 100 from result 1542:1547 arg1 urine 1603:1607 urine 1603:1607 urine of patients with PCa 1603:1628 CONCLUSIONS The urinary vesicle-associated PSA extraction ratio is increased in PCa which is a direct result of the abundant presence of extracellular vesicles in urine of patients with PCa. 28360190 3 101 theme vesicle-associated 416:433 arg1 PSA 462:464 PSA 462:464 PSA 462:464 We investigated if prostatic protein N-glycosylation profiles were related to urinary vesicle-associated prostate-specific antigen (PSA) extractability and if this parameter showed diagnostic potential for PCa. 28360190 3 101 theme vesicle-associated 416:433 arg1 antigen 453:459 vesicle-associated prostate-specific antigen 416:459 urinary vesicle-associated prostate-specific antigen (PSA) extractability 408:480 We investigated if prostatic protein N-glycosylation profiles were related to urinary vesicle-associated prostate-specific antigen (PSA) extractability and if this parameter showed diagnostic potential for PCa. 28360190 4 102 theme Urinary 549:555 arg1 vesicles 571:578 Urinary extracellular vesicles 549:578 METHODS Urinary extracellular vesicles 541:578 METHODS Urinary extracellular vesicles were visualised using transmission electron microscopy. 28360190 9 103 theme PSA 1209:1211 arg1 ratio 1224:1228 vesicle-associated PSA extraction ratio 1190:1228 vesicle-associated PSA extraction ratio 1190:1228 Next, vesicle-associated PSA extraction ratio was correlated to biantennary core-fucosylation (p=0.003). 28360190 8 104 located present 1048:1054 arg1 urine 1059:1063 urine 1059:1063 urine of patients with PCa versus patients with BPH resulting in a higher vesicle-associated PSA extraction ratio (p<0.001) 1059:1181 RESULTS Urinary extracellular vesicles with a diameter of approximately 100 nm were more abundantly present in urine of patients with PCa versus patients with BPH resulting in a higher vesicle-associated PSA extraction ratio (p<0.001). 28360190 8 104 located present 1048:1054 arg2 RESULTS 948:954 RESULTS 948:954 RESULTS Urinary extracellular vesicles with a diameter of approximately 100 nm 948:1025 RESULTS Urinary extracellular vesicles with a diameter of approximately 100 nm were more abundantly present in urine of patients with PCa versus patients with BPH resulting in a higher vesicle-associated PSA extraction ratio (p<0.001). 28360190 3 105 theme diagnostic 511:520 arg1 potential 522:530 diagnostic potential 511:530 diagnostic potential for PCa 511:538 We investigated if prostatic protein N-glycosylation profiles were related to urinary vesicle-associated prostate-specific antigen (PSA) extractability and if this parameter showed diagnostic potential for PCa. 28360190 8 106 theme 100 nm 1020:1025 arg1 diameter 994:1001 a diameter 992:1001 a diameter of approximately 100 nm 992:1025 RESULTS Urinary extracellular vesicles with a diameter of approximately 100 nm were more abundantly present in urine of patients with PCa versus patients with BPH resulting in a higher vesicle-associated PSA extraction ratio (p<0.001). 28360190 6 107 theme prostate 817:824 arg1 hyperplasia 826:836 benign prostate hyperplasia 810:836 benign prostate hyperplasia (BPH; n=122) 810:849 Diagnostic value was assessed between benign prostate hyperplasia (BPH; n=122) and patients with PCa (n=85). 28360190 6 107 theme prostate 817:824 arg1 BPH 839:841 BPH 839:841 BPH; n=122 839:848 Diagnostic value was assessed between benign prostate hyperplasia (BPH; n=122) and patients with PCa (n=85). 27891581 1 0 theme IgG 297:299 arg1 alloantibodies 301:314 maternal anti-RBC IgG alloantibodies 279:314 maternal anti-RBC IgG alloantibodies 279:314 Haemolytic disease of the fetus and newborn (HDFN) is a severe disease in which fetal red blood cells (RBC) are destroyed by maternal anti-RBC IgG alloantibodies. 27891581 5 1 theme IgG 994:996 arg1 fraction 998:1005 the total IgG fraction 984:1005 the total IgG fraction 984:1005 Anti-c, -E and -K show - independent of the event that had led to immunisation - a different kind of Fc-glycosylation compared to that of the total IgG fraction, but with less pronounced differences compared to anti-D. 27891581 0 2 dep fetus 135:139 arg1 the 131:133 the 131:133 the 131:133 Antigen specificity determines anti-red blood cell IgG-Fc alloantibody glycosylation and thereby severity of haemolytic disease of the fetus and newborn. 27891581 4 3 from relation 783:790 arg1 type 730:733 the type 726:733 the type of Fc-tail glycosylation of these antibodies in relation to the trigger of immunisation and pregnancy outcome 726:843 Here, we analysed 230 pregnant women with anti-c, -E or -K alloantibodies from a prospective screening cohort and investigated the type of Fc-tail glycosylation of these antibodies in relation to the trigger of immunisation and pregnancy outcome. 27891581 7 4 gly glycosylation 1232:1244 arg1 antibodies 1258:1267 anti-RBC antibodies 1249:1267 anti-RBC antibodies 1249:1267 IgG-Fc glycosylation of anti-RBC antibodies is shaped depending on the antigen. 27891581 3 5 theme anti-D 442:447 arg1 glycosylation 425:437 N-linked glycosylation 416:437 N-linked glycosylation of anti-D 416:447 We recently found N-linked glycosylation of anti-D to be skewed towards low fucosylation, thereby increasing the affinity to IgG-Fc receptor IIIa and IIIb, which correlated with HDFN disease severity. 27891581 1 6 theme fetal 234:238 arg1 RBC 257:259 RBC 257:259 RBC 257:259 Haemolytic disease of the fetus and newborn (HDFN) is a severe disease in which fetal red blood cells (RBC) are destroyed by maternal anti-RBC IgG alloantibodies. 27891581 1 6 theme fetal 234:238 arg1 cells 250:254 fetal red blood cells 234:254 fetal red blood cells (RBC) 234:260 Haemolytic disease of the fetus and newborn (HDFN) is a severe disease in which fetal red blood cells (RBC) are destroyed by maternal anti-RBC IgG alloantibodies. 27891581 0 7 theme haemolytic 109:118 arg1 disease 120:126 haemolytic disease 109:126 haemolytic disease 109:126 Antigen specificity determines anti-red blood cell IgG-Fc alloantibody glycosylation and thereby severity of haemolytic disease of the fetus and newborn. 27891581 5 8 theme event 890:894 arg1 independent 871:881 independent 871:881 independent 871:881 Anti-c, -E and -K show - independent of the event that had led to immunisation - a different kind of Fc-glycosylation compared to that of the total IgG fraction, but with less pronounced differences compared to anti-D. 27891581 6 9 theme anti-K 1164:1169 arg1 Fc-fucosylation 1171:1185 low anti-K Fc-fucosylation 1160:1185 low anti-K Fc-fucosylation 1160:1185 High Fc-galactosylation and sialylation of anti-c correlated with HDFN disease severity, while low anti-K Fc-fucosylation correlated with severe fetal anaemia. 27891581 3 10 theme low 470:472 arg1 fucosylation 474:485 low fucosylation 470:485 low fucosylation 470:485 We recently found N-linked glycosylation of anti-D to be skewed towards low fucosylation, thereby increasing the affinity to IgG-Fc receptor IIIa and IIIb, which correlated with HDFN disease severity. 27891581 1 11 theme red 240:242 arg1 RBC 257:259 RBC 257:259 RBC 257:259 Haemolytic disease of the fetus and newborn (HDFN) is a severe disease in which fetal red blood cells (RBC) are destroyed by maternal anti-RBC IgG alloantibodies. 27891581 1 11 theme red 240:242 arg1 cells 250:254 fetal red blood cells 234:254 fetal red blood cells (RBC) 234:260 Haemolytic disease of the fetus and newborn (HDFN) is a severe disease in which fetal red blood cells (RBC) are destroyed by maternal anti-RBC IgG alloantibodies. 27891581 4 12 theme -E 649:650 arg1 alloantibodies 658:671 anti-c, -E or -K alloantibodies 641:671 anti-c, -E or -K alloantibodies from a prospective screening cohort 641:707 Here, we analysed 230 pregnant women with anti-c, -E or -K alloantibodies from a prospective screening cohort and investigated the type of Fc-tail glycosylation of these antibodies in relation to the trigger of immunisation and pregnancy outcome. 27891581 6 13 theme low 1160:1162 arg1 Fc-fucosylation 1171:1185 low anti-K Fc-fucosylation 1160:1185 low anti-K Fc-fucosylation 1160:1185 High Fc-galactosylation and sialylation of anti-c correlated with HDFN disease severity, while low anti-K Fc-fucosylation correlated with severe fetal anaemia. 27891581 1 14 theme blood 244:248 arg1 RBC 257:259 RBC 257:259 RBC 257:259 Haemolytic disease of the fetus and newborn (HDFN) is a severe disease in which fetal red blood cells (RBC) are destroyed by maternal anti-RBC IgG alloantibodies. 27891581 1 14 theme blood 244:248 arg1 cells 250:254 fetal red blood cells 234:254 fetal red blood cells (RBC) 234:260 Haemolytic disease of the fetus and newborn (HDFN) is a severe disease in which fetal red blood cells (RBC) are destroyed by maternal anti-RBC IgG alloantibodies. 27891581 4 15 theme prospective 680:690 arg1 cohort 702:707 a prospective screening cohort 678:707 a prospective screening cohort 678:707 Here, we analysed 230 pregnant women with anti-c, -E or -K alloantibodies from a prospective screening cohort and investigated the type of Fc-tail glycosylation of these antibodies in relation to the trigger of immunisation and pregnancy outcome. 27891581 0 16 theme disease 120:126 arg1 severity 97:104 severity 97:104 anti-red blood cell IgG-Fc alloantibody glycosylation and thereby severity of haemolytic disease of the fetus and newborn 31:151 Antigen specificity determines anti-red blood cell IgG-Fc alloantibody glycosylation and thereby severity of haemolytic disease of the fetus and newborn. 27891581 5 17 theme total 988:992 arg1 fraction 998:1005 the total IgG fraction 984:1005 the total IgG fraction 984:1005 Anti-c, -E and -K show - independent of the event that had led to immunisation - a different kind of Fc-glycosylation compared to that of the total IgG fraction, but with less pronounced differences compared to anti-D. 27891581 4 18 theme glycosylation 746:758 arg1 type 730:733 the type 726:733 the type of Fc-tail glycosylation of these antibodies in relation to the trigger of immunisation and pregnancy outcome 726:843 Here, we analysed 230 pregnant women with anti-c, -E or -K alloantibodies from a prospective screening cohort and investigated the type of Fc-tail glycosylation of these antibodies in relation to the trigger of immunisation and pregnancy outcome. 27891581 4 19 with women 630:634 arg1 alloantibodies 658:671 anti-c, -E or -K alloantibodies 641:671 anti-c, -E or -K alloantibodies from a prospective screening cohort 641:707 Here, we analysed 230 pregnant women with anti-c, -E or -K alloantibodies from a prospective screening cohort and investigated the type of Fc-tail glycosylation of these antibodies in relation to the trigger of immunisation and pregnancy outcome. 27891581 1 20 theme fetus 180:184 arg1 disease 217:223 a severe disease 208:223 a severe disease in which fetal red blood cells (RBC) are destroyed by maternal anti-RBC IgG alloantibodies 208:314 Haemolytic disease of the fetus and newborn (HDFN) is a severe disease in which fetal red blood cells (RBC) are destroyed by maternal anti-RBC IgG alloantibodies. 27891581 1 20 theme fetus 180:184 arg1 disease 165:171 Haemolytic disease 154:171 Haemolytic disease of the fetus and newborn (HDFN) 154:203 Haemolytic disease of the fetus and newborn (HDFN) is a severe disease in which fetal red blood cells (RBC) are destroyed by maternal anti-RBC IgG alloantibodies. 27891581 4 21 from glycosylation 746:758 arg1 relation 783:790 relation 783:790 relation to the trigger of immunisation and pregnancy outcome 783:843 Here, we analysed 230 pregnant women with anti-c, -E or -K alloantibodies from a prospective screening cohort and investigated the type of Fc-tail glycosylation of these antibodies in relation to the trigger of immunisation and pregnancy outcome. 27891581 4 22 theme antibodies 769:778 arg1 glycosylation 746:758 Fc-tail glycosylation 738:758 Fc-tail glycosylation of these antibodies in relation to the trigger of immunisation and pregnancy outcome 738:843 Here, we analysed 230 pregnant women with anti-c, -E or -K alloantibodies from a prospective screening cohort and investigated the type of Fc-tail glycosylation of these antibodies in relation to the trigger of immunisation and pregnancy outcome. 27891581 3 23 gly glycosylation 425:437 arg1 anti-D 442:447 anti-D 442:447 anti-D 442:447 We recently found N-linked glycosylation of anti-D to be skewed towards low fucosylation, thereby increasing the affinity to IgG-Fc receptor IIIa and IIIb, which correlated with HDFN disease severity. 27891581 6 24 theme fetal 1210:1214 arg1 anaemia 1216:1222 severe fetal anaemia 1203:1222 severe fetal anaemia 1203:1222 High Fc-galactosylation and sialylation of anti-c correlated with HDFN disease severity, while low anti-K Fc-fucosylation correlated with severe fetal anaemia. 27891581 0 25 theme Antigen 0:6 arg1 specificity 8:18 Antigen specificity 0:18 Antigen specificity 0:18 Antigen specificity determines anti-red blood cell IgG-Fc alloantibody glycosylation and thereby severity of haemolytic disease of the fetus and newborn. 27891581 6 26 theme disease 1136:1142 arg1 severity 1144:1151 HDFN disease severity 1131:1151 HDFN disease severity 1131:1151 High Fc-galactosylation and sialylation of anti-c correlated with HDFN disease severity, while low anti-K Fc-fucosylation correlated with severe fetal anaemia. 27891581 1 27 theme newborn 190:196 arg1 disease 217:223 a severe disease 208:223 a severe disease in which fetal red blood cells (RBC) are destroyed by maternal anti-RBC IgG alloantibodies 208:314 Haemolytic disease of the fetus and newborn (HDFN) is a severe disease in which fetal red blood cells (RBC) are destroyed by maternal anti-RBC IgG alloantibodies. 27891581 1 27 theme newborn 190:196 arg1 disease 165:171 Haemolytic disease 154:171 Haemolytic disease of the fetus and newborn (HDFN) 154:203 Haemolytic disease of the fetus and newborn (HDFN) is a severe disease in which fetal red blood cells (RBC) are destroyed by maternal anti-RBC IgG alloantibodies. 27891581 0 28 theme anti-red 31:38 arg1 cell 46:49 anti-red blood cell 31:49 anti-red blood cell IgG-Fc alloantibody glycosylation and thereby severity of haemolytic disease of the fetus and newborn 31:151 Antigen specificity determines anti-red blood cell IgG-Fc alloantibody glycosylation and thereby severity of haemolytic disease of the fetus and newborn. 27891581 8 29 used used 1374:1377 arg2 features 1311:1318 These features 1305:1318 These features 1305:1318 These features influence their clinical potency and may therefore be used to predict severity and identify those needing treatment. 27891581 0 30 theme fetus 135:139 arg1 severity 97:104 severity 97:104 anti-red blood cell IgG-Fc alloantibody glycosylation and thereby severity of haemolytic disease of the fetus and newborn 31:151 Antigen specificity determines anti-red blood cell IgG-Fc alloantibody glycosylation and thereby severity of haemolytic disease of the fetus and newborn. 27891581 6 31 theme anti-c 1108:1113 arg1 sialylation 1093:1103 sialylation 1093:1103 sialylation 1093:1103 High Fc-galactosylation and sialylation of anti-c correlated with HDFN disease severity, while low anti-K Fc-fucosylation correlated with severe fetal anaemia. 27891581 6 31 theme anti-c 1108:1113 arg1 Fc-galactosylation 1070:1087 High Fc-galactosylation 1065:1087 High Fc-galactosylation 1065:1087 High Fc-galactosylation and sialylation of anti-c correlated with HDFN disease severity, while low anti-K Fc-fucosylation correlated with severe fetal anaemia. 27891581 4 32 theme -K 655:656 arg1 alloantibodies 658:671 anti-c, -E or -K alloantibodies 641:671 anti-c, -E or -K alloantibodies from a prospective screening cohort 641:707 Here, we analysed 230 pregnant women with anti-c, -E or -K alloantibodies from a prospective screening cohort and investigated the type of Fc-tail glycosylation of these antibodies in relation to the trigger of immunisation and pregnancy outcome. 27891581 6 33 theme HDFN 1131:1134 arg1 severity 1144:1151 HDFN disease severity 1131:1151 HDFN disease severity 1131:1151 High Fc-galactosylation and sialylation of anti-c correlated with HDFN disease severity, while low anti-K Fc-fucosylation correlated with severe fetal anaemia. 27891581 4 34 gly glycosylation 746:758 arg1 relation 783:790 relation 783:790 relation to the trigger of immunisation and pregnancy outcome 783:843 Here, we analysed 230 pregnant women with anti-c, -E or -K alloantibodies from a prospective screening cohort and investigated the type of Fc-tail glycosylation of these antibodies in relation to the trigger of immunisation and pregnancy outcome. 27891581 4 34 gly glycosylation 746:758 arg1 antibodies 769:778 these antibodies 763:778 these antibodies 763:778 Here, we analysed 230 pregnant women with anti-c, -E or -K alloantibodies from a prospective screening cohort and investigated the type of Fc-tail glycosylation of these antibodies in relation to the trigger of immunisation and pregnancy outcome. 27891581 6 35 theme High 1065:1068 arg1 Fc-galactosylation 1070:1087 High Fc-galactosylation 1065:1087 High Fc-galactosylation 1065:1087 High Fc-galactosylation and sialylation of anti-c correlated with HDFN disease severity, while low anti-K Fc-fucosylation correlated with severe fetal anaemia. 27891581 4 36 theme pregnancy 827:835 arg1 outcome 837:843 pregnancy outcome 827:843 pregnancy outcome 827:843 Here, we analysed 230 pregnant women with anti-c, -E or -K alloantibodies from a prospective screening cohort and investigated the type of Fc-tail glycosylation of these antibodies in relation to the trigger of immunisation and pregnancy outcome. 27891581 5 37 theme Fc-glycosylation 947:962 arg1 kind 939:942 a different kind 927:942 a different kind of Fc-glycosylation 927:962 Anti-c, -E and -K show - independent of the event that had led to immunisation - a different kind of Fc-glycosylation compared to that of the total IgG fraction, but with less pronounced differences compared to anti-D. 27891581 0 38 theme cell 46:49 arg1 glycosylation 71:83 anti-red blood cell IgG-Fc alloantibody glycosylation 31:83 anti-red blood cell IgG-Fc alloantibody glycosylation and thereby severity of haemolytic disease of the fetus and newborn 31:151 Antigen specificity determines anti-red blood cell IgG-Fc alloantibody glycosylation and thereby severity of haemolytic disease of the fetus and newborn. 27891581 0 39 theme newborn 145:151 arg1 severity 97:104 severity 97:104 anti-red blood cell IgG-Fc alloantibody glycosylation and thereby severity of haemolytic disease of the fetus and newborn 31:151 Antigen specificity determines anti-red blood cell IgG-Fc alloantibody glycosylation and thereby severity of haemolytic disease of the fetus and newborn. 27891581 3 40 theme HDFN 576:579 arg1 severity 589:596 HDFN disease severity 576:596 HDFN disease severity 576:596 We recently found N-linked glycosylation of anti-D to be skewed towards low fucosylation, thereby increasing the affinity to IgG-Fc receptor IIIa and IIIb, which correlated with HDFN disease severity. 27891581 3 41 theme IgG-Fc 523:528 arg1 receptor 530:537 IgG-Fc receptor IIIa and IIIb, which correlated with HDFN disease severity 523:596 receptor 530:537 We recently found N-linked glycosylation of anti-D to be skewed towards low fucosylation, thereby increasing the affinity to IgG-Fc receptor IIIa and IIIb, which correlated with HDFN disease severity. 27891581 3 42 dep receptor 530:537 arg1 IIIb 548:551 IIIb 548:551 IIIb 548:551 We recently found N-linked glycosylation of anti-D to be skewed towards low fucosylation, thereby increasing the affinity to IgG-Fc receptor IIIa and IIIb, which correlated with HDFN disease severity. 27891581 3 42 dep receptor 530:537 arg1 IIIa 539:542 IIIa 539:542 IIIa 539:542 We recently found N-linked glycosylation of anti-D to be skewed towards low fucosylation, thereby increasing the affinity to IgG-Fc receptor IIIa and IIIb, which correlated with HDFN disease severity. 27891581 0 43 theme blood 40:44 arg1 cell 46:49 anti-red blood cell 31:49 anti-red blood cell IgG-Fc alloantibody glycosylation and thereby severity of haemolytic disease of the fetus and newborn 31:151 Antigen specificity determines anti-red blood cell IgG-Fc alloantibody glycosylation and thereby severity of haemolytic disease of the fetus and newborn. 27891581 0 44 theme alloantibody 58:69 arg1 glycosylation 71:83 anti-red blood cell IgG-Fc alloantibody glycosylation 31:83 anti-red blood cell IgG-Fc alloantibody glycosylation and thereby severity of haemolytic disease of the fetus and newborn 31:151 Antigen specificity determines anti-red blood cell IgG-Fc alloantibody glycosylation and thereby severity of haemolytic disease of the fetus and newborn. 27891581 5 45 theme pronounced 1022:1031 arg1 differences 1033:1043 less pronounced differences 1017:1043 less pronounced differences compared to anti-D 1017:1062 Anti-c, -E and -K show - independent of the event that had led to immunisation - a different kind of Fc-glycosylation compared to that of the total IgG fraction, but with less pronounced differences compared to anti-D. 27891581 4 46 theme Fc-tail 738:744 arg1 glycosylation 746:758 Fc-tail glycosylation 738:758 Fc-tail glycosylation of these antibodies in relation to the trigger of immunisation and pregnancy outcome 738:843 Here, we analysed 230 pregnant women with anti-c, -E or -K alloantibodies from a prospective screening cohort and investigated the type of Fc-tail glycosylation of these antibodies in relation to the trigger of immunisation and pregnancy outcome. 27891581 6 47 theme severe 1203:1208 arg1 anaemia 1216:1222 severe fetal anaemia 1203:1222 severe fetal anaemia 1203:1222 High Fc-galactosylation and sialylation of anti-c correlated with HDFN disease severity, while low anti-K Fc-fucosylation correlated with severe fetal anaemia. 27891581 3 48 theme N-linked 416:423 arg1 glycosylation 425:437 N-linked glycosylation 416:437 N-linked glycosylation of anti-D 416:447 We recently found N-linked glycosylation of anti-D to be skewed towards low fucosylation, thereby increasing the affinity to IgG-Fc receptor IIIa and IIIb, which correlated with HDFN disease severity. 27891581 0 49 theme IgG-Fc 51:56 arg1 glycosylation 71:83 anti-red blood cell IgG-Fc alloantibody glycosylation 31:83 anti-red blood cell IgG-Fc alloantibody glycosylation and thereby severity of haemolytic disease of the fetus and newborn 31:151 Antigen specificity determines anti-red blood cell IgG-Fc alloantibody glycosylation and thereby severity of haemolytic disease of the fetus and newborn. 27891581 4 50 theme outcome 837:843 arg1 trigger 799:805 the trigger 795:805 the trigger of immunisation and pregnancy outcome 795:843 Here, we analysed 230 pregnant women with anti-c, -E or -K alloantibodies from a prospective screening cohort and investigated the type of Fc-tail glycosylation of these antibodies in relation to the trigger of immunisation and pregnancy outcome. 27891581 1 51 dep fetus 180:184 arg1 the 176:178 the 176:178 the 176:178 Haemolytic disease of the fetus and newborn (HDFN) is a severe disease in which fetal red blood cells (RBC) are destroyed by maternal anti-RBC IgG alloantibodies. 27891581 4 52 from type 730:733 arg1 relation 783:790 relation 783:790 relation to the trigger of immunisation and pregnancy outcome 783:843 Here, we analysed 230 pregnant women with anti-c, -E or -K alloantibodies from a prospective screening cohort and investigated the type of Fc-tail glycosylation of these antibodies in relation to the trigger of immunisation and pregnancy outcome. 27891581 4 53 theme pregnant 621:628 arg1 women 630:634 230 pregnant women 617:634 230 pregnant women with anti-c, -E or -K alloantibodies from a prospective screening cohort 617:707 Here, we analysed 230 pregnant women with anti-c, -E or -K alloantibodies from a prospective screening cohort and investigated the type of Fc-tail glycosylation of these antibodies in relation to the trigger of immunisation and pregnancy outcome. 27891581 1 54 theme maternal 279:286 arg1 alloantibodies 301:314 maternal anti-RBC IgG alloantibodies 279:314 maternal anti-RBC IgG alloantibodies 279:314 Haemolytic disease of the fetus and newborn (HDFN) is a severe disease in which fetal red blood cells (RBC) are destroyed by maternal anti-RBC IgG alloantibodies. 27891581 3 55 link N-linked 416:423 arg1 glycosylation 425:437 N-linked glycosylation 416:437 N-linked glycosylation of anti-D 416:447 We recently found N-linked glycosylation of anti-D to be skewed towards low fucosylation, thereby increasing the affinity to IgG-Fc receptor IIIa and IIIb, which correlated with HDFN disease severity. 27891581 5 56 theme different 929:937 arg1 kind 939:942 a different kind 927:942 a different kind of Fc-glycosylation 927:962 Anti-c, -E and -K show - independent of the event that had led to immunisation - a different kind of Fc-glycosylation compared to that of the total IgG fraction, but with less pronounced differences compared to anti-D. 27891581 8 57 theme clinical 1336:1343 arg1 potency 1345:1351 their clinical potency 1330:1351 their clinical potency 1330:1351 These features influence their clinical potency and may therefore be used to predict severity and identify those needing treatment. 27891581 4 58 theme anti-c 641:646 arg1 alloantibodies 658:671 anti-c, -E or -K alloantibodies 641:671 anti-c, -E or -K alloantibodies from a prospective screening cohort 641:707 Here, we analysed 230 pregnant women with anti-c, -E or -K alloantibodies from a prospective screening cohort and investigated the type of Fc-tail glycosylation of these antibodies in relation to the trigger of immunisation and pregnancy outcome. 27891581 4 59 theme immunisation 810:821 arg1 trigger 799:805 the trigger 795:805 the trigger of immunisation and pregnancy outcome 795:843 Here, we analysed 230 pregnant women with anti-c, -E or -K alloantibodies from a prospective screening cohort and investigated the type of Fc-tail glycosylation of these antibodies in relation to the trigger of immunisation and pregnancy outcome. 27891581 3 60 theme disease 581:587 arg1 severity 589:596 HDFN disease severity 576:596 HDFN disease severity 576:596 We recently found N-linked glycosylation of anti-D to be skewed towards low fucosylation, thereby increasing the affinity to IgG-Fc receptor IIIa and IIIb, which correlated with HDFN disease severity. 27891581 4 61 theme screening 692:700 arg1 cohort 702:707 a prospective screening cohort 678:707 a prospective screening cohort 678:707 Here, we analysed 230 pregnant women with anti-c, -E or -K alloantibodies from a prospective screening cohort and investigated the type of Fc-tail glycosylation of these antibodies in relation to the trigger of immunisation and pregnancy outcome. 27891581 7 62 theme IgG-Fc 1225:1230 arg1 glycosylation 1232:1244 IgG-Fc glycosylation 1225:1244 IgG-Fc glycosylation of anti-RBC antibodies 1225:1267 IgG-Fc glycosylation of anti-RBC antibodies is shaped depending on the antigen. 27891581 1 63 theme severe 210:215 arg1 disease 217:223 a severe disease 208:223 a severe disease in which fetal red blood cells (RBC) are destroyed by maternal anti-RBC IgG alloantibodies 208:314 Haemolytic disease of the fetus and newborn (HDFN) is a severe disease in which fetal red blood cells (RBC) are destroyed by maternal anti-RBC IgG alloantibodies. 27891581 1 63 theme severe 210:215 arg1 disease 165:171 Haemolytic disease 154:171 Haemolytic disease of the fetus and newborn (HDFN) 154:203 Haemolytic disease of the fetus and newborn (HDFN) is a severe disease in which fetal red blood cells (RBC) are destroyed by maternal anti-RBC IgG alloantibodies. 27891581 6 64 gly sialylation 1093:1103 arg1 anti-c 1108:1113 anti-c 1108:1113 anti-c 1108:1113 High Fc-galactosylation and sialylation of anti-c correlated with HDFN disease severity, while low anti-K Fc-fucosylation correlated with severe fetal anaemia. 27891581 7 65 theme anti-RBC 1249:1256 arg1 antibodies 1258:1267 anti-RBC antibodies 1249:1267 anti-RBC antibodies 1249:1267 IgG-Fc glycosylation of anti-RBC antibodies is shaped depending on the antigen. 27891581 1 66 theme anti-RBC 288:295 arg1 alloantibodies 301:314 maternal anti-RBC IgG alloantibodies 279:314 maternal anti-RBC IgG alloantibodies 279:314 Haemolytic disease of the fetus and newborn (HDFN) is a severe disease in which fetal red blood cells (RBC) are destroyed by maternal anti-RBC IgG alloantibodies. 27891581 7 67 theme antibodies 1258:1267 arg1 glycosylation 1232:1244 IgG-Fc glycosylation 1225:1244 IgG-Fc glycosylation of anti-RBC antibodies 1225:1267 IgG-Fc glycosylation of anti-RBC antibodies is shaped depending on the antigen. 27891581 4 68 from cohort 702:707 arg1 alloantibodies 658:671 anti-c, -E or -K alloantibodies 641:671 anti-c, -E or -K alloantibodies from a prospective screening cohort 641:707 Here, we analysed 230 pregnant women with anti-c, -E or -K alloantibodies from a prospective screening cohort and investigated the type of Fc-tail glycosylation of these antibodies in relation to the trigger of immunisation and pregnancy outcome. 27891581 1 69 theme Haemolytic 154:163 arg1 disease 217:223 a severe disease 208:223 a severe disease in which fetal red blood cells (RBC) are destroyed by maternal anti-RBC IgG alloantibodies 208:314 Haemolytic disease of the fetus and newborn (HDFN) is a severe disease in which fetal red blood cells (RBC) are destroyed by maternal anti-RBC IgG alloantibodies. 27891581 1 69 theme Haemolytic 154:163 arg1 disease 165:171 Haemolytic disease 154:171 Haemolytic disease of the fetus and newborn (HDFN) 154:203 Haemolytic disease of the fetus and newborn (HDFN) is a severe disease in which fetal red blood cells (RBC) are destroyed by maternal anti-RBC IgG alloantibodies. 27017954 0 0 theme clinical 83:90 arg1 outcome 92:98 clinical outcome 83:98 clinical outcome in alloimmune thrombocytopenia 83:129 Glycosylation pattern of anti-platelet IgG is stable during pregnancy and predicts clinical outcome in alloimmune thrombocytopenia. 27017954 3 1 theme IgG 540:542 arg1 Fc-glycosylation 544:559 IgG Fc-glycosylation 540:559 IgG Fc-glycosylation towards platelet and red blood cell antigens 540:604 We recently found IgG Fc-glycosylation towards platelet and red blood cell antigens to be skewed towards decreased fucosylation, increased galactosylation and sialylation. 27017954 1 2 theme maternal 267:274 arg1 alloantibodies 294:307 maternal anti-platelet IgG alloantibodies 267:307 maternal anti-platelet IgG alloantibodies 267:307 Fetal or neonatal alloimmune thrombocytopenia (FNAIT) is a potentially life-threatening disease where fetal platelets are destroyed by maternal anti-platelet IgG alloantibodies. 27017954 4 3 theme antibodies 765:774 arg1 affinity 738:745 the affinity 734:745 the affinity of the pathogenic antibodies to FcγRIIIa and FcγRIIIb, and hence platelet destruction 734:831 The lowered core-fucosylation increases the affinity of the pathogenic antibodies to FcγRIIIa and FcγRIIIb, and hence platelet destruction. 27017954 1 4 theme anti-platelet 276:288 arg1 alloantibodies 294:307 maternal anti-platelet IgG alloantibodies 267:307 maternal anti-platelet IgG alloantibodies 267:307 Fetal or neonatal alloimmune thrombocytopenia (FNAIT) is a potentially life-threatening disease where fetal platelets are destroyed by maternal anti-platelet IgG alloantibodies. 27017954 3 5 theme blood 586:590 arg1 cell 592:595 red blood cell 582:595 red blood cell 582:595 We recently found IgG Fc-glycosylation towards platelet and red blood cell antigens to be skewed towards decreased fucosylation, increased galactosylation and sialylation. 27017954 6 6 theme subsequent 1190:1199 arg1 pregnancies 1201:1211 subsequent pregnancies 1190:1211 subsequent pregnancies 1190:1211 Besides a significant decrease in Fc-fucosylation after the first pregnancy (P = 0·0124), Fc-glycosylation levels remained stable during and after pregnancy and in subsequent pregnancies. 27017954 1 7 theme IgG 290:292 arg1 alloantibodies 294:307 maternal anti-platelet IgG alloantibodies 267:307 maternal anti-platelet IgG alloantibodies 267:307 Fetal or neonatal alloimmune thrombocytopenia (FNAIT) is a potentially life-threatening disease where fetal platelets are destroyed by maternal anti-platelet IgG alloantibodies. 27017954 3 8 theme cell 592:595 arg1 antigens 597:604 platelet and red blood cell antigens 569:604 platelet and red blood cell antigens 569:604 We recently found IgG Fc-glycosylation towards platelet and red blood cell antigens to be skewed towards decreased fucosylation, increased galactosylation and sialylation. 27017954 2 9 theme clinical 314:321 arg1 outcome 323:329 The clinical outcome 310:329 The clinical outcome 310:329 The clinical outcome varies from asymptomatic, to petechiae or intracranial haemorrhage, but no marker has shown reliable correlation with severity, making screening for FNAIT impractical and highly inefficient. 27017954 5 10 theme IgG1 916:919 arg1 glycans 864:870 the N-linked glycans 851:870 the N-linked glycans of human platelet antigen (HPA)-1a specific IgG1 851:919 Here we analysed the N-linked glycans of human platelet antigen (HPA)-1a specific IgG1 with mass spectrometry in large series of FNAIT cases (n = 166) including longitudinal samples (n = 26). 27017954 7 11 theme anti-HPA-1a 1263:1273 arg1 P = 0·006 1290:1298 P = 0·006 1290:1298 P = 0·006 1290:1298 Multiple logistic regression analysis identified anti-HPA-1a -fucosylation (P = 0·006) combined with galactosylation (P = 0·021) and antibody level (P = 0·038) correlated with bleeding severity, making these parameters a feasible marker in screening for severe cases of FNAIT. 27017954 7 11 theme anti-HPA-1a 1263:1273 arg1 -fucosylation 1275:1287 anti-HPA-1a -fucosylation 1263:1287 anti-HPA-1a -fucosylation (P = 0·006) combined with galactosylation (P = 0·021) 1263:1341 Multiple logistic regression analysis identified anti-HPA-1a -fucosylation (P = 0·006) combined with galactosylation (P = 0·021) and antibody level (P = 0·038) correlated with bleeding severity, making these parameters a feasible marker in screening for severe cases of FNAIT. 27017954 2 12 with correlation 432:442 arg1 severity 449:456 severity 449:456 severity 449:456 The clinical outcome varies from asymptomatic, to petechiae or intracranial haemorrhage, but no marker has shown reliable correlation with severity, making screening for FNAIT impractical and highly inefficient. 27017954 7 13 theme bleeding 1390:1397 arg1 severity 1399:1406 bleeding severity 1390:1406 bleeding severity 1390:1406 Multiple logistic regression analysis identified anti-HPA-1a -fucosylation (P = 0·006) combined with galactosylation (P = 0·021) and antibody level (P = 0·038) correlated with bleeding severity, making these parameters a feasible marker in screening for severe cases of FNAIT. 27017954 2 14 theme reliable 423:430 arg1 correlation 432:442 reliable correlation 423:442 reliable correlation with severity 423:456 The clinical outcome varies from asymptomatic, to petechiae or intracranial haemorrhage, but no marker has shown reliable correlation with severity, making screening for FNAIT impractical and highly inefficient. 27017954 0 15 theme alloimmune 103:112 arg1 thrombocytopenia 114:129 alloimmune thrombocytopenia 103:129 alloimmune thrombocytopenia 103:129 Glycosylation pattern of anti-platelet IgG is stable during pregnancy and predicts clinical outcome in alloimmune thrombocytopenia. 27017954 3 16 theme red 582:584 arg1 cell 592:595 red blood cell 582:595 red blood cell 582:595 We recently found IgG Fc-glycosylation towards platelet and red blood cell antigens to be skewed towards decreased fucosylation, increased galactosylation and sialylation. 27017954 6 17 theme Fc-glycosylation 1116:1131 arg1 levels 1133:1138 Fc-glycosylation levels 1116:1138 Fc-glycosylation levels 1116:1138 Besides a significant decrease in Fc-fucosylation after the first pregnancy (P = 0·0124), Fc-glycosylation levels remained stable during and after pregnancy and in subsequent pregnancies. 27017954 5 18 theme human 875:879 arg1 IgG1 916:919 human platelet antigen (HPA)-1a specific IgG1 875:919 human platelet antigen (HPA)-1a specific IgG1 875:919 Here we analysed the N-linked glycans of human platelet antigen (HPA)-1a specific IgG1 with mass spectrometry in large series of FNAIT cases (n = 166) including longitudinal samples (n = 26). 27017954 6 19 from decrease 1048:1055 arg1 Fc-fucosylation 1060:1074 Fc-fucosylation 1060:1074 Fc-fucosylation after the first pregnancy (P = 0·0124) 1060:1113 Besides a significant decrease in Fc-fucosylation after the first pregnancy (P = 0·0124), Fc-glycosylation levels remained stable during and after pregnancy and in subsequent pregnancies. 27017954 7 20 theme FNAIT 1484:1488 arg1 cases 1475:1479 severe cases 1468:1479 severe cases of FNAIT 1468:1488 Multiple logistic regression analysis identified anti-HPA-1a -fucosylation (P = 0·006) combined with galactosylation (P = 0·021) and antibody level (P = 0·038) correlated with bleeding severity, making these parameters a feasible marker in screening for severe cases of FNAIT. 27017954 7 21 from marker 1444:1449 arg1 screening 1454:1462 screening 1454:1462 screening 1454:1462 Multiple logistic regression analysis identified anti-HPA-1a -fucosylation (P = 0·006) combined with galactosylation (P = 0·021) and antibody level (P = 0·038) correlated with bleeding severity, making these parameters a feasible marker in screening for severe cases of FNAIT. 27017954 5 22 theme mass 926:929 arg1 spectrometry 931:942 mass spectrometry 926:942 mass spectrometry 926:942 Here we analysed the N-linked glycans of human platelet antigen (HPA)-1a specific IgG1 with mass spectrometry in large series of FNAIT cases (n = 166) including longitudinal samples (n = 26). 27017954 0 23 theme Glycosylation 0:12 arg1 pattern 14:20 Glycosylation pattern 0:20 Glycosylation pattern of anti-platelet IgG 0:41 Glycosylation pattern of anti-platelet IgG is stable during pregnancy and predicts clinical outcome in alloimmune thrombocytopenia. 27017954 7 24 theme Multiple 1214:1221 arg1 analysis 1243:1250 Multiple logistic regression analysis 1214:1250 Multiple logistic regression analysis 1214:1250 Multiple logistic regression analysis identified anti-HPA-1a -fucosylation (P = 0·006) combined with galactosylation (P = 0·021) and antibody level (P = 0·038) correlated with bleeding severity, making these parameters a feasible marker in screening for severe cases of FNAIT. 27017954 5 25 theme large 947:951 arg1 series 953:958 large series 947:958 large series of FNAIT cases (n = 166) including longitudinal samples (n = 26) 947:1023 Here we analysed the N-linked glycans of human platelet antigen (HPA)-1a specific IgG1 with mass spectrometry in large series of FNAIT cases (n = 166) including longitudinal samples (n = 26). 27017954 0 26 theme anti-platelet 25:37 arg1 IgG 39:41 anti-platelet IgG 25:41 anti-platelet IgG 25:41 Glycosylation pattern of anti-platelet IgG is stable during pregnancy and predicts clinical outcome in alloimmune thrombocytopenia. 27017954 5 27 theme platelet 881:888 arg1 IgG1 916:919 human platelet antigen (HPA)-1a specific IgG1 875:919 human platelet antigen (HPA)-1a specific IgG1 875:919 Here we analysed the N-linked glycans of human platelet antigen (HPA)-1a specific IgG1 with mass spectrometry in large series of FNAIT cases (n = 166) including longitudinal samples (n = 26). 27017954 5 28 link N-linked 855:862 arg1 glycans 864:870 the N-linked glycans 851:870 the N-linked glycans of human platelet antigen (HPA)-1a specific IgG1 851:919 Here we analysed the N-linked glycans of human platelet antigen (HPA)-1a specific IgG1 with mass spectrometry in large series of FNAIT cases (n = 166) including longitudinal samples (n = 26). 27017954 4 29 theme destruction 821:831 arg1 affinity 738:745 the affinity 734:745 the affinity of the pathogenic antibodies to FcγRIIIa and FcγRIIIb, and hence platelet destruction 734:831 The lowered core-fucosylation increases the affinity of the pathogenic antibodies to FcγRIIIa and FcγRIIIb, and hence platelet destruction. 27017954 1 30 theme life-threatening 203:218 arg1 disease 220:226 a potentially life-threatening disease 189:226 a potentially life-threatening disease where fetal platelets are destroyed by maternal anti-platelet IgG alloantibodies 189:307 Fetal or neonatal alloimmune thrombocytopenia (FNAIT) is a potentially life-threatening disease where fetal platelets are destroyed by maternal anti-platelet IgG alloantibodies. 27017954 1 30 theme life-threatening 203:218 arg1 thrombocytopenia 161:176 alloimmune thrombocytopenia 150:176 Fetal or neonatal alloimmune thrombocytopenia (FNAIT) 132:184 Fetal or neonatal alloimmune thrombocytopenia (FNAIT) is a potentially life-threatening disease where fetal platelets are destroyed by maternal anti-platelet IgG alloantibodies. 27017954 7 31 theme regression 1232:1241 arg1 analysis 1243:1250 Multiple logistic regression analysis 1214:1250 Multiple logistic regression analysis 1214:1250 Multiple logistic regression analysis identified anti-HPA-1a -fucosylation (P = 0·006) combined with galactosylation (P = 0·021) and antibody level (P = 0·038) correlated with bleeding severity, making these parameters a feasible marker in screening for severe cases of FNAIT. 27017954 4 32 theme platelet 812:819 arg1 destruction 821:831 platelet destruction 812:831 platelet destruction 812:831 The lowered core-fucosylation increases the affinity of the pathogenic antibodies to FcγRIIIa and FcγRIIIb, and hence platelet destruction. 27017954 4 33 theme pathogenic 754:763 arg1 antibodies 765:774 the pathogenic antibodies 750:774 the pathogenic antibodies to FcγRIIIa and FcγRIIIb 750:799 The lowered core-fucosylation increases the affinity of the pathogenic antibodies to FcγRIIIa and FcγRIIIb, and hence platelet destruction. 27017954 2 34 theme inefficient 509:519 arg1 screening 466:474 screening 466:474 screening for FNAIT impractical and highly inefficient 466:519 The clinical outcome varies from asymptomatic, to petechiae or intracranial haemorrhage, but no marker has shown reliable correlation with severity, making screening for FNAIT impractical and highly inefficient. 27017954 5 35 theme cases 969:973 arg1 series 953:958 large series 947:958 large series of FNAIT cases (n = 166) including longitudinal samples (n = 26) 947:1023 Here we analysed the N-linked glycans of human platelet antigen (HPA)-1a specific IgG1 with mass spectrometry in large series of FNAIT cases (n = 166) including longitudinal samples (n = 26). 27017954 4 36 theme lowered 698:704 arg1 core-fucosylation 706:722 The lowered core-fucosylation 694:722 The lowered core-fucosylation 694:722 The lowered core-fucosylation increases the affinity of the pathogenic antibodies to FcγRIIIa and FcγRIIIb, and hence platelet destruction. 27017954 5 37 theme -1a 903:905 arg1 IgG1 916:919 human platelet antigen (HPA)-1a specific IgG1 875:919 human platelet antigen (HPA)-1a specific IgG1 875:919 Here we analysed the N-linked glycans of human platelet antigen (HPA)-1a specific IgG1 with mass spectrometry in large series of FNAIT cases (n = 166) including longitudinal samples (n = 26). 27017954 0 38 theme IgG 39:41 arg1 pattern 14:20 Glycosylation pattern 0:20 Glycosylation pattern of anti-platelet IgG 0:41 Glycosylation pattern of anti-platelet IgG is stable during pregnancy and predicts clinical outcome in alloimmune thrombocytopenia. 27017954 5 39 theme N-linked 855:862 arg1 glycans 864:870 the N-linked glycans 851:870 the N-linked glycans of human platelet antigen (HPA)-1a specific IgG1 851:919 Here we analysed the N-linked glycans of human platelet antigen (HPA)-1a specific IgG1 with mass spectrometry in large series of FNAIT cases (n = 166) including longitudinal samples (n = 26). 27017954 6 40 theme significant 1036:1046 arg1 decrease 1048:1055 a significant decrease 1034:1055 a significant decrease in Fc-fucosylation after the first pregnancy (P = 0·0124) 1034:1113 Besides a significant decrease in Fc-fucosylation after the first pregnancy (P = 0·0124), Fc-glycosylation levels remained stable during and after pregnancy and in subsequent pregnancies. 27017954 5 41 theme antigen 890:896 arg1 IgG1 916:919 human platelet antigen (HPA)-1a specific IgG1 875:919 human platelet antigen (HPA)-1a specific IgG1 875:919 Here we analysed the N-linked glycans of human platelet antigen (HPA)-1a specific IgG1 with mass spectrometry in large series of FNAIT cases (n = 166) including longitudinal samples (n = 26). 27017954 5 42 theme specific 907:914 arg1 IgG1 916:919 human platelet antigen (HPA)-1a specific IgG1 875:919 human platelet antigen (HPA)-1a specific IgG1 875:919 Here we analysed the N-linked glycans of human platelet antigen (HPA)-1a specific IgG1 with mass spectrometry in large series of FNAIT cases (n = 166) including longitudinal samples (n = 26). 27017954 1 43 theme fetal 234:238 arg1 platelets 240:248 fetal platelets 234:248 fetal platelets 234:248 Fetal or neonatal alloimmune thrombocytopenia (FNAIT) is a potentially life-threatening disease where fetal platelets are destroyed by maternal anti-platelet IgG alloantibodies. 27017954 6 44 theme first 1086:1090 arg1 P = 0·0124 1103:1112 P = 0·0124 1103:1112 P = 0·0124 1103:1112 Besides a significant decrease in Fc-fucosylation after the first pregnancy (P = 0·0124), Fc-glycosylation levels remained stable during and after pregnancy and in subsequent pregnancies. 27017954 6 44 theme first 1086:1090 arg1 pregnancy 1092:1100 the first pregnancy 1082:1100 the first pregnancy (P = 0·0124) 1082:1113 Besides a significant decrease in Fc-fucosylation after the first pregnancy (P = 0·0124), Fc-glycosylation levels remained stable during and after pregnancy and in subsequent pregnancies. 27017954 2 45 theme intracranial 373:384 arg1 haemorrhage 386:396 intracranial haemorrhage 373:396 intracranial haemorrhage 373:396 The clinical outcome varies from asymptomatic, to petechiae or intracranial haemorrhage, but no marker has shown reliable correlation with severity, making screening for FNAIT impractical and highly inefficient. 27017954 2 46 theme impractical 486:496 arg1 screening 466:474 screening 466:474 screening for FNAIT impractical and highly inefficient 466:519 The clinical outcome varies from asymptomatic, to petechiae or intracranial haemorrhage, but no marker has shown reliable correlation with severity, making screening for FNAIT impractical and highly inefficient. 27017954 3 47 theme decreased 627:635 arg1 fucosylation 637:648 decreased fucosylation 627:648 decreased fucosylation 627:648 We recently found IgG Fc-glycosylation towards platelet and red blood cell antigens to be skewed towards decreased fucosylation, increased galactosylation and sialylation. 27017954 1 48 theme Fetal 132:136 arg1 disease 220:226 a potentially life-threatening disease 189:226 a potentially life-threatening disease where fetal platelets are destroyed by maternal anti-platelet IgG alloantibodies 189:307 Fetal or neonatal alloimmune thrombocytopenia (FNAIT) is a potentially life-threatening disease where fetal platelets are destroyed by maternal anti-platelet IgG alloantibodies. 27017954 1 48 theme Fetal 132:136 arg1 thrombocytopenia 161:176 alloimmune thrombocytopenia 150:176 Fetal or neonatal alloimmune thrombocytopenia (FNAIT) 132:184 Fetal or neonatal alloimmune thrombocytopenia (FNAIT) is a potentially life-threatening disease where fetal platelets are destroyed by maternal anti-platelet IgG alloantibodies. 27017954 1 48 theme Fetal 132:136 arg1 FNAIT 179:183 FNAIT 179:183 FNAIT 179:183 Fetal or neonatal alloimmune thrombocytopenia (FNAIT) is a potentially life-threatening disease where fetal platelets are destroyed by maternal anti-platelet IgG alloantibodies. 27017954 7 49 theme logistic 1223:1230 arg1 analysis 1243:1250 Multiple logistic regression analysis 1214:1250 Multiple logistic regression analysis 1214:1250 Multiple logistic regression analysis identified anti-HPA-1a -fucosylation (P = 0·006) combined with galactosylation (P = 0·021) and antibody level (P = 0·038) correlated with bleeding severity, making these parameters a feasible marker in screening for severe cases of FNAIT. 27017954 7 50 theme feasible 1435:1442 arg1 marker 1444:1449 a feasible marker 1433:1449 a feasible marker in screening for severe cases of FNAIT 1433:1488 Multiple logistic regression analysis identified anti-HPA-1a -fucosylation (P = 0·006) combined with galactosylation (P = 0·021) and antibody level (P = 0·038) correlated with bleeding severity, making these parameters a feasible marker in screening for severe cases of FNAIT. 27017954 7 51 theme severe 1468:1473 arg1 cases 1475:1479 severe cases 1468:1479 severe cases of FNAIT 1468:1488 Multiple logistic regression analysis identified anti-HPA-1a -fucosylation (P = 0·006) combined with galactosylation (P = 0·021) and antibody level (P = 0·038) correlated with bleeding severity, making these parameters a feasible marker in screening for severe cases of FNAIT. 27017954 7 52 theme antibody 1347:1354 arg1 level 1356:1360 antibody level 1347:1360 antibody level (P = 0·038) 1347:1372 Multiple logistic regression analysis identified anti-HPA-1a -fucosylation (P = 0·006) combined with galactosylation (P = 0·021) and antibody level (P = 0·038) correlated with bleeding severity, making these parameters a feasible marker in screening for severe cases of FNAIT. 27017954 7 52 theme antibody 1347:1354 arg1 P = 0·038 1363:1371 P = 0·038 1363:1371 P = 0·038 1363:1371 Multiple logistic regression analysis identified anti-HPA-1a -fucosylation (P = 0·006) combined with galactosylation (P = 0·021) and antibody level (P = 0·038) correlated with bleeding severity, making these parameters a feasible marker in screening for severe cases of FNAIT. 27017954 5 53 theme longitudinal 995:1006 arg1 n = 26 1017:1022 n = 26 1017:1022 n = 26 1017:1022 Here we analysed the N-linked glycans of human platelet antigen (HPA)-1a specific IgG1 with mass spectrometry in large series of FNAIT cases (n = 166) including longitudinal samples (n = 26). 27017954 5 53 theme longitudinal 995:1006 arg1 samples 1008:1014 longitudinal samples 995:1014 longitudinal samples (n = 26) 995:1023 Here we analysed the N-linked glycans of human platelet antigen (HPA)-1a specific IgG1 with mass spectrometry in large series of FNAIT cases (n = 166) including longitudinal samples (n = 26). 27017954 5 54 theme FNAIT 963:967 arg1 cases 969:973 FNAIT cases 963:973 FNAIT cases (n = 166) including longitudinal samples (n = 26) 963:1023 Here we analysed the N-linked glycans of human platelet antigen (HPA)-1a specific IgG1 with mass spectrometry in large series of FNAIT cases (n = 166) including longitudinal samples (n = 26). 27017954 5 54 theme FNAIT 963:967 arg1 samples 1008:1014 longitudinal samples 995:1014 longitudinal samples (n = 26) 995:1023 Here we analysed the N-linked glycans of human platelet antigen (HPA)-1a specific IgG1 with mass spectrometry in large series of FNAIT cases (n = 166) including longitudinal samples (n = 26). 27017954 5 54 theme FNAIT 963:967 arg1 n = 166 976:982 n = 166 976:982 n = 166 976:982 Here we analysed the N-linked glycans of human platelet antigen (HPA)-1a specific IgG1 with mass spectrometry in large series of FNAIT cases (n = 166) including longitudinal samples (n = 26). 27017954 1 55 theme neonatal 141:148 arg1 disease 220:226 a potentially life-threatening disease 189:226 a potentially life-threatening disease where fetal platelets are destroyed by maternal anti-platelet IgG alloantibodies 189:307 Fetal or neonatal alloimmune thrombocytopenia (FNAIT) is a potentially life-threatening disease where fetal platelets are destroyed by maternal anti-platelet IgG alloantibodies. 27017954 1 55 theme neonatal 141:148 arg1 thrombocytopenia 161:176 alloimmune thrombocytopenia 150:176 Fetal or neonatal alloimmune thrombocytopenia (FNAIT) 132:184 Fetal or neonatal alloimmune thrombocytopenia (FNAIT) is a potentially life-threatening disease where fetal platelets are destroyed by maternal anti-platelet IgG alloantibodies. 27017954 1 55 theme neonatal 141:148 arg1 FNAIT 179:183 FNAIT 179:183 FNAIT 179:183 Fetal or neonatal alloimmune thrombocytopenia (FNAIT) is a potentially life-threatening disease where fetal platelets are destroyed by maternal anti-platelet IgG alloantibodies. 27017954 0 56 from outcome 92:98 arg1 thrombocytopenia 114:129 alloimmune thrombocytopenia 103:129 alloimmune thrombocytopenia 103:129 Glycosylation pattern of anti-platelet IgG is stable during pregnancy and predicts clinical outcome in alloimmune thrombocytopenia. 27017954 3 57 theme increased 651:659 arg1 galactosylation 661:675 increased galactosylation 651:675 increased galactosylation 651:675 We recently found IgG Fc-glycosylation towards platelet and red blood cell antigens to be skewed towards decreased fucosylation, increased galactosylation and sialylation. 27017954 5 58 theme HPA 899:901 arg1 IgG1 916:919 human platelet antigen (HPA)-1a specific IgG1 875:919 human platelet antigen (HPA)-1a specific IgG1 875:919 Here we analysed the N-linked glycans of human platelet antigen (HPA)-1a specific IgG1 with mass spectrometry in large series of FNAIT cases (n = 166) including longitudinal samples (n = 26). 27017954 1 59 theme alloimmune 150:159 arg1 disease 220:226 a potentially life-threatening disease 189:226 a potentially life-threatening disease where fetal platelets are destroyed by maternal anti-platelet IgG alloantibodies 189:307 Fetal or neonatal alloimmune thrombocytopenia (FNAIT) is a potentially life-threatening disease where fetal platelets are destroyed by maternal anti-platelet IgG alloantibodies. 27017954 1 59 theme alloimmune 150:159 arg1 thrombocytopenia 161:176 alloimmune thrombocytopenia 150:176 Fetal or neonatal alloimmune thrombocytopenia (FNAIT) 132:184 Fetal or neonatal alloimmune thrombocytopenia (FNAIT) is a potentially life-threatening disease where fetal platelets are destroyed by maternal anti-platelet IgG alloantibodies. 27017954 1 59 theme alloimmune 150:159 arg1 FNAIT 179:183 FNAIT 179:183 FNAIT 179:183 Fetal or neonatal alloimmune thrombocytopenia (FNAIT) is a potentially life-threatening disease where fetal platelets are destroyed by maternal anti-platelet IgG alloantibodies. 27017954 3 60 theme platelet 569:576 arg1 antigens 597:604 platelet and red blood cell antigens 569:604 platelet and red blood cell antigens 569:604 We recently found IgG Fc-glycosylation towards platelet and red blood cell antigens to be skewed towards decreased fucosylation, increased galactosylation and sialylation. 26629951 0 0 theme human 82:86 arg1 cells 98:102 human dendritic cells 82:102 human dendritic cells 82:102 DC-SIGN as an attachment factor mediates Japanese encephalitis virus infection of human dendritic cells via interaction with a single high-mannose residue of viral E glycoprotein. 26629951 3 1 theme high-mannose 666:677 arg1 glycan 688:693 the high-mannose N-linked glycan 662:693 the high-mannose N-linked glycan at N154 of E glycoprotein 662:719 Moreover, the high-mannose N-linked glycan at N154 of E glycoprotein was shown to be crucial for JEV binding to DC-SIGN and subsequent internalization, while mutation of DC-SIGN internalization motif did not affect JEV uptake and internalization. 26629951 3 1 theme high-mannose 666:677 arg1 crucial 737:743 crucial 737:743 crucial 737:743 Moreover, the high-mannose N-linked glycan at N154 of E glycoprotein was shown to be crucial for JEV binding to DC-SIGN and subsequent internalization, while mutation of DC-SIGN internalization motif did not affect JEV uptake and internalization. 26629951 3 2 theme DC-SIGN 822:828 arg1 motif 846:850 DC-SIGN internalization motif 822:850 DC-SIGN internalization motif 822:850 Moreover, the high-mannose N-linked glycan at N154 of E glycoprotein was shown to be crucial for JEV binding to DC-SIGN and subsequent internalization, while mutation of DC-SIGN internalization motif did not affect JEV uptake and internalization. 26629951 2 3 theme E 518:518 arg1 glycoprotein 504:515 JEV envelope glycoprotein 491:515 JEV envelope glycoprotein (E glycoprotein) 491:532 In the current study, following the demonstration of JEV productive infection in DCs, we revealed that the interaction between JEV envelope glycoprotein (E glycoprotein) and DC-SIGN was important for such infection as evidenced by antibody neutralization and siRNA knockdown experiments. 26629951 2 3 theme E 518:518 arg1 glycoprotein 520:531 E glycoprotein 518:531 E glycoprotein 518:531 In the current study, following the demonstration of JEV productive infection in DCs, we revealed that the interaction between JEV envelope glycoprotein (E glycoprotein) and DC-SIGN was important for such infection as evidenced by antibody neutralization and siRNA knockdown experiments. 26629951 3 4 theme subsequent 776:785 arg1 internalization 787:801 subsequent internalization 776:801 subsequent internalization 776:801 Moreover, the high-mannose N-linked glycan at N154 of E glycoprotein was shown to be crucial for JEV binding to DC-SIGN and subsequent internalization, while mutation of DC-SIGN internalization motif did not affect JEV uptake and internalization. 26629951 1 5 theme Japanese 313:320 arg1 JEV 342:344 JEV 342:344 JEV 342:344 The skin-resident dendritic cells (DCs) are thought to be the first defender to encounter incoming viruses and likely play a role in Japanese encephalitis virus (JEV) early infection. 26629951 1 5 theme Japanese 313:320 arg1 virus 335:339 Japanese encephalitis virus 313:339 Japanese encephalitis virus (JEV) early infection 313:361 The skin-resident dendritic cells (DCs) are thought to be the first defender to encounter incoming viruses and likely play a role in Japanese encephalitis virus (JEV) early infection. 26629951 0 6 theme glycoprotein 166:177 arg1 glycoprotein 166:177 viral E glycoprotein 158:177 viral E glycoprotein 158:177 DC-SIGN as an attachment factor mediates Japanese encephalitis virus infection of human dendritic cells via interaction with a single high-mannose residue of viral E glycoprotein. 26629951 0 6 theme glycoprotein 166:177 arg1 residue 147:153 a single high-mannose residue 125:153 a single high-mannose residue of viral E glycoprotein 125:177 DC-SIGN as an attachment factor mediates Japanese encephalitis virus infection of human dendritic cells via interaction with a single high-mannose residue of viral E glycoprotein. 26629951 2 7 from demonstration 400:412 arg1 DCs 445:447 DCs 445:447 DCs 445:447 In the current study, following the demonstration of JEV productive infection in DCs, we revealed that the interaction between JEV envelope glycoprotein (E glycoprotein) and DC-SIGN was important for such infection as evidenced by antibody neutralization and siRNA knockdown experiments. 26629951 0 8 theme cells 98:102 arg1 infection 69:77 Japanese encephalitis virus infection 41:77 Japanese encephalitis virus infection of human dendritic cells 41:102 DC-SIGN as an attachment factor mediates Japanese encephalitis virus infection of human dendritic cells via interaction with a single high-mannose residue of viral E glycoprotein. 26629951 1 9 theme encephalitis 322:333 arg1 JEV 342:344 JEV 342:344 JEV 342:344 The skin-resident dendritic cells (DCs) are thought to be the first defender to encounter incoming viruses and likely play a role in Japanese encephalitis virus (JEV) early infection. 26629951 1 9 theme encephalitis 322:333 arg1 virus 335:339 Japanese encephalitis virus 313:339 Japanese encephalitis virus (JEV) early infection 313:361 The skin-resident dendritic cells (DCs) are thought to be the first defender to encounter incoming viruses and likely play a role in Japanese encephalitis virus (JEV) early infection. 26629951 3 10 theme internalization 830:844 arg1 motif 846:850 DC-SIGN internalization motif 822:850 DC-SIGN internalization motif 822:850 Moreover, the high-mannose N-linked glycan at N154 of E glycoprotein was shown to be crucial for JEV binding to DC-SIGN and subsequent internalization, while mutation of DC-SIGN internalization motif did not affect JEV uptake and internalization. 26629951 1 11 theme first 242:246 arg1 cells 208:212 The skin-resident dendritic cells 180:212 The skin-resident dendritic cells (DCs) 180:218 The skin-resident dendritic cells (DCs) are thought to be the first defender to encounter incoming viruses and likely play a role in Japanese encephalitis virus (JEV) early infection. 26629951 1 11 theme first 242:246 arg1 defender 248:255 the first defender 238:255 the first defender to encounter incoming viruses 238:285 The skin-resident dendritic cells (DCs) are thought to be the first defender to encounter incoming viruses and likely play a role in Japanese encephalitis virus (JEV) early infection. 26629951 0 12 theme dendritic 88:96 arg1 cells 98:102 human dendritic cells 82:102 human dendritic cells 82:102 DC-SIGN as an attachment factor mediates Japanese encephalitis virus infection of human dendritic cells via interaction with a single high-mannose residue of viral E glycoprotein. 26629951 1 13 theme virus 335:339 arg1 infection 353:361 Japanese encephalitis virus (JEV) early infection 313:361 Japanese encephalitis virus (JEV) early infection 313:361 The skin-resident dendritic cells (DCs) are thought to be the first defender to encounter incoming viruses and likely play a role in Japanese encephalitis virus (JEV) early infection. 26629951 2 14 theme antibody 595:602 arg1 neutralization 604:617 antibody neutralization 595:617 antibody neutralization 595:617 In the current study, following the demonstration of JEV productive infection in DCs, we revealed that the interaction between JEV envelope glycoprotein (E glycoprotein) and DC-SIGN was important for such infection as evidenced by antibody neutralization and siRNA knockdown experiments. 26629951 3 15 link N-linked 679:686 arg1 glycan 688:693 the high-mannose N-linked glycan 662:693 the high-mannose N-linked glycan at N154 of E glycoprotein 662:719 Moreover, the high-mannose N-linked glycan at N154 of E glycoprotein was shown to be crucial for JEV binding to DC-SIGN and subsequent internalization, while mutation of DC-SIGN internalization motif did not affect JEV uptake and internalization. 26629951 3 15 link N-linked 679:686 arg1 crucial 737:743 crucial 737:743 crucial 737:743 Moreover, the high-mannose N-linked glycan at N154 of E glycoprotein was shown to be crucial for JEV binding to DC-SIGN and subsequent internalization, while mutation of DC-SIGN internalization motif did not affect JEV uptake and internalization. 26629951 3 16 gly glycoprotein 708:719 arg1 glycoprotein 708:719 E glycoprotein 706:719 E glycoprotein 706:719 Moreover, the high-mannose N-linked glycan at N154 of E glycoprotein was shown to be crucial for JEV binding to DC-SIGN and subsequent internalization, while mutation of DC-SIGN internalization motif did not affect JEV uptake and internalization. 26629951 0 17 gly glycoprotein 166:177 arg1 glycoprotein 166:177 viral E glycoprotein 158:177 viral E glycoprotein 158:177 DC-SIGN as an attachment factor mediates Japanese encephalitis virus infection of human dendritic cells via interaction with a single high-mannose residue of viral E glycoprotein. 26629951 2 18 theme JEV 417:419 arg1 infection 432:440 JEV productive infection 417:440 JEV productive infection in DCs 417:447 In the current study, following the demonstration of JEV productive infection in DCs, we revealed that the interaction between JEV envelope glycoprotein (E glycoprotein) and DC-SIGN was important for such infection as evidenced by antibody neutralization and siRNA knockdown experiments. 26629951 3 19 theme N-linked 679:686 arg1 glycan 688:693 the high-mannose N-linked glycan 662:693 the high-mannose N-linked glycan at N154 of E glycoprotein 662:719 Moreover, the high-mannose N-linked glycan at N154 of E glycoprotein was shown to be crucial for JEV binding to DC-SIGN and subsequent internalization, while mutation of DC-SIGN internalization motif did not affect JEV uptake and internalization. 26629951 3 19 theme N-linked 679:686 arg1 crucial 737:743 crucial 737:743 crucial 737:743 Moreover, the high-mannose N-linked glycan at N154 of E glycoprotein was shown to be crucial for JEV binding to DC-SIGN and subsequent internalization, while mutation of DC-SIGN internalization motif did not affect JEV uptake and internalization. 26629951 0 20 with interaction 108:118 arg1 glycoprotein 166:177 viral E glycoprotein 158:177 viral E glycoprotein 158:177 DC-SIGN as an attachment factor mediates Japanese encephalitis virus infection of human dendritic cells via interaction with a single high-mannose residue of viral E glycoprotein. 26629951 0 20 with interaction 108:118 arg1 residue 147:153 a single high-mannose residue 125:153 a single high-mannose residue of viral E glycoprotein 125:177 DC-SIGN as an attachment factor mediates Japanese encephalitis virus infection of human dendritic cells via interaction with a single high-mannose residue of viral E glycoprotein. 26629951 4 21 theme entry 989:993 arg1 receptor 995:1002 an entry receptor 986:1002 an attachment factor rather than an entry receptor for JEV 953:1010 These data together suggest that DC-SIGN functions as an attachment factor rather than an entry receptor for JEV. 26629951 4 21 theme entry 989:993 arg1 DC-SIGN 932:938 DC-SIGN 932:938 DC-SIGN 932:938 These data together suggest that DC-SIGN functions as an attachment factor rather than an entry receptor for JEV. 26629951 2 22 from infection 432:440 arg1 DCs 445:447 DCs 445:447 DCs 445:447 In the current study, following the demonstration of JEV productive infection in DCs, we revealed that the interaction between JEV envelope glycoprotein (E glycoprotein) and DC-SIGN was important for such infection as evidenced by antibody neutralization and siRNA knockdown experiments. 26629951 5 23 theme DC-SIGN 1066:1072 arg1 significance 1050:1061 the potential significance 1036:1061 the potential significance of DC-SIGN in JEV early infection 1036:1095 Our findings highlight the potential significance of DC-SIGN in JEV early infection, providing a basis for further understanding how JEV exploits DC-SIGN to gain access to dendritic cells. 26629951 2 24 theme envelope 495:502 arg1 glycoprotein 504:515 JEV envelope glycoprotein 491:515 JEV envelope glycoprotein (E glycoprotein) 491:532 In the current study, following the demonstration of JEV productive infection in DCs, we revealed that the interaction between JEV envelope glycoprotein (E glycoprotein) and DC-SIGN was important for such infection as evidenced by antibody neutralization and siRNA knockdown experiments. 26629951 2 24 theme envelope 495:502 arg1 glycoprotein 520:531 E glycoprotein 518:531 E glycoprotein 518:531 In the current study, following the demonstration of JEV productive infection in DCs, we revealed that the interaction between JEV envelope glycoprotein (E glycoprotein) and DC-SIGN was important for such infection as evidenced by antibody neutralization and siRNA knockdown experiments. 26629951 3 25 theme glycoprotein 708:719 arg1 N154 698:701 N154 698:701 N154 of E glycoprotein 698:719 Moreover, the high-mannose N-linked glycan at N154 of E glycoprotein was shown to be crucial for JEV binding to DC-SIGN and subsequent internalization, while mutation of DC-SIGN internalization motif did not affect JEV uptake and internalization. 26629951 2 26 theme such 564:567 arg1 infection 569:577 such infection 564:577 such infection 564:577 In the current study, following the demonstration of JEV productive infection in DCs, we revealed that the interaction between JEV envelope glycoprotein (E glycoprotein) and DC-SIGN was important for such infection as evidenced by antibody neutralization and siRNA knockdown experiments. 26629951 2 27 theme knockdown 629:637 arg1 experiments 639:649 siRNA knockdown experiments 623:649 siRNA knockdown experiments 623:649 In the current study, following the demonstration of JEV productive infection in DCs, we revealed that the interaction between JEV envelope glycoprotein (E glycoprotein) and DC-SIGN was important for such infection as evidenced by antibody neutralization and siRNA knockdown experiments. 26629951 3 28 theme JEV 867:869 arg1 uptake 871:876 JEV uptake 867:876 JEV uptake 867:876 Moreover, the high-mannose N-linked glycan at N154 of E glycoprotein was shown to be crucial for JEV binding to DC-SIGN and subsequent internalization, while mutation of DC-SIGN internalization motif did not affect JEV uptake and internalization. 26629951 1 29 theme skin-resident 184:196 arg1 cells 208:212 The skin-resident dendritic cells 180:212 The skin-resident dendritic cells (DCs) 180:218 The skin-resident dendritic cells (DCs) are thought to be the first defender to encounter incoming viruses and likely play a role in Japanese encephalitis virus (JEV) early infection. 26629951 1 29 theme skin-resident 184:196 arg1 defender 248:255 the first defender 238:255 the first defender to encounter incoming viruses 238:285 The skin-resident dendritic cells (DCs) are thought to be the first defender to encounter incoming viruses and likely play a role in Japanese encephalitis virus (JEV) early infection. 26629951 1 29 theme skin-resident 184:196 arg1 DCs 215:217 DCs 215:217 DCs 215:217 The skin-resident dendritic cells (DCs) are thought to be the first defender to encounter incoming viruses and likely play a role in Japanese encephalitis virus (JEV) early infection. 26629951 0 30 theme attachment 14:23 arg1 factor 25:30 an attachment factor 11:30 an attachment factor 11:30 DC-SIGN as an attachment factor mediates Japanese encephalitis virus infection of human dendritic cells via interaction with a single high-mannose residue of viral E glycoprotein. 26629951 1 31 theme encounter 260:268 arg1 viruses 279:285 encounter incoming viruses 260:285 encounter incoming viruses 260:285 The skin-resident dendritic cells (DCs) are thought to be the first defender to encounter incoming viruses and likely play a role in Japanese encephalitis virus (JEV) early infection. 26629951 2 32 theme siRNA 623:627 arg1 experiments 639:649 siRNA knockdown experiments 623:649 siRNA knockdown experiments 623:649 In the current study, following the demonstration of JEV productive infection in DCs, we revealed that the interaction between JEV envelope glycoprotein (E glycoprotein) and DC-SIGN was important for such infection as evidenced by antibody neutralization and siRNA knockdown experiments. 26629951 1 33 theme dendritic 198:206 arg1 cells 208:212 The skin-resident dendritic cells 180:212 The skin-resident dendritic cells (DCs) 180:218 The skin-resident dendritic cells (DCs) are thought to be the first defender to encounter incoming viruses and likely play a role in Japanese encephalitis virus (JEV) early infection. 26629951 1 33 theme dendritic 198:206 arg1 defender 248:255 the first defender 238:255 the first defender to encounter incoming viruses 238:285 The skin-resident dendritic cells (DCs) are thought to be the first defender to encounter incoming viruses and likely play a role in Japanese encephalitis virus (JEV) early infection. 26629951 1 33 theme dendritic 198:206 arg1 DCs 215:217 DCs 215:217 DCs 215:217 The skin-resident dendritic cells (DCs) are thought to be the first defender to encounter incoming viruses and likely play a role in Japanese encephalitis virus (JEV) early infection. 26629951 3 34 from N154 698:701 arg1 glycan 688:693 the high-mannose N-linked glycan 662:693 the high-mannose N-linked glycan at N154 of E glycoprotein 662:719 Moreover, the high-mannose N-linked glycan at N154 of E glycoprotein was shown to be crucial for JEV binding to DC-SIGN and subsequent internalization, while mutation of DC-SIGN internalization motif did not affect JEV uptake and internalization. 26629951 3 34 from N154 698:701 arg1 crucial 737:743 crucial 737:743 crucial 737:743 Moreover, the high-mannose N-linked glycan at N154 of E glycoprotein was shown to be crucial for JEV binding to DC-SIGN and subsequent internalization, while mutation of DC-SIGN internalization motif did not affect JEV uptake and internalization. 26629951 1 35 theme incoming 270:277 arg1 viruses 279:285 encounter incoming viruses 260:285 encounter incoming viruses 260:285 The skin-resident dendritic cells (DCs) are thought to be the first defender to encounter incoming viruses and likely play a role in Japanese encephalitis virus (JEV) early infection. 26629951 1 36 theme early 347:351 arg1 infection 353:361 Japanese encephalitis virus (JEV) early infection 313:361 Japanese encephalitis virus (JEV) early infection 313:361 The skin-resident dendritic cells (DCs) are thought to be the first defender to encounter incoming viruses and likely play a role in Japanese encephalitis virus (JEV) early infection. 26629951 2 37 theme productive 421:430 arg1 infection 432:440 JEV productive infection 417:440 JEV productive infection in DCs 417:447 In the current study, following the demonstration of JEV productive infection in DCs, we revealed that the interaction between JEV envelope glycoprotein (E glycoprotein) and DC-SIGN was important for such infection as evidenced by antibody neutralization and siRNA knockdown experiments. 26629951 3 38 theme E 706:706 arg1 glycoprotein 708:719 E glycoprotein 706:719 E glycoprotein 706:719 Moreover, the high-mannose N-linked glycan at N154 of E glycoprotein was shown to be crucial for JEV binding to DC-SIGN and subsequent internalization, while mutation of DC-SIGN internalization motif did not affect JEV uptake and internalization. 26629951 0 39 theme high-mannose 134:145 arg1 glycoprotein 166:177 viral E glycoprotein 158:177 viral E glycoprotein 158:177 DC-SIGN as an attachment factor mediates Japanese encephalitis virus infection of human dendritic cells via interaction with a single high-mannose residue of viral E glycoprotein. 26629951 0 39 theme high-mannose 134:145 arg1 residue 147:153 a single high-mannose residue 125:153 a single high-mannose residue of viral E glycoprotein 125:177 DC-SIGN as an attachment factor mediates Japanese encephalitis virus infection of human dendritic cells via interaction with a single high-mannose residue of viral E glycoprotein. 26629951 2 40 from DCs 445:447 arg1 demonstration 400:412 the demonstration 396:412 the demonstration of JEV productive infection in DCs 396:447 In the current study, following the demonstration of JEV productive infection in DCs, we revealed that the interaction between JEV envelope glycoprotein (E glycoprotein) and DC-SIGN was important for such infection as evidenced by antibody neutralization and siRNA knockdown experiments. 26629951 2 41 theme current 371:377 arg1 study 379:383 the current study 367:383 the current study 367:383 In the current study, following the demonstration of JEV productive infection in DCs, we revealed that the interaction between JEV envelope glycoprotein (E glycoprotein) and DC-SIGN was important for such infection as evidenced by antibody neutralization and siRNA knockdown experiments. 26629951 2 42 theme infection 432:440 arg1 demonstration 400:412 the demonstration 396:412 the demonstration of JEV productive infection in DCs 396:447 In the current study, following the demonstration of JEV productive infection in DCs, we revealed that the interaction between JEV envelope glycoprotein (E glycoprotein) and DC-SIGN was important for such infection as evidenced by antibody neutralization and siRNA knockdown experiments. 26629951 0 43 theme single 127:132 arg1 glycoprotein 166:177 viral E glycoprotein 158:177 viral E glycoprotein 158:177 DC-SIGN as an attachment factor mediates Japanese encephalitis virus infection of human dendritic cells via interaction with a single high-mannose residue of viral E glycoprotein. 26629951 0 43 theme single 127:132 arg1 residue 147:153 a single high-mannose residue 125:153 a single high-mannose residue of viral E glycoprotein 125:177 DC-SIGN as an attachment factor mediates Japanese encephalitis virus infection of human dendritic cells via interaction with a single high-mannose residue of viral E glycoprotein. 26629951 5 44 theme potential 1040:1048 arg1 significance 1050:1061 the potential significance 1036:1061 the potential significance of DC-SIGN in JEV early infection 1036:1095 Our findings highlight the potential significance of DC-SIGN in JEV early infection, providing a basis for further understanding how JEV exploits DC-SIGN to gain access to dendritic cells. 26629951 2 45 theme JEV 491:493 arg1 glycoprotein 504:515 JEV envelope glycoprotein 491:515 JEV envelope glycoprotein (E glycoprotein) 491:532 In the current study, following the demonstration of JEV productive infection in DCs, we revealed that the interaction between JEV envelope glycoprotein (E glycoprotein) and DC-SIGN was important for such infection as evidenced by antibody neutralization and siRNA knockdown experiments. 26629951 2 45 theme JEV 491:493 arg1 glycoprotein 520:531 E glycoprotein 518:531 E glycoprotein 518:531 In the current study, following the demonstration of JEV productive infection in DCs, we revealed that the interaction between JEV envelope glycoprotein (E glycoprotein) and DC-SIGN was important for such infection as evidenced by antibody neutralization and siRNA knockdown experiments. 26629951 0 46 theme encephalitis 50:61 arg1 virus 63:67 Japanese encephalitis virus 41:67 Japanese encephalitis virus infection of human dendritic cells 41:102 DC-SIGN as an attachment factor mediates Japanese encephalitis virus infection of human dendritic cells via interaction with a single high-mannose residue of viral E glycoprotein. 26629951 0 47 theme Japanese 41:48 arg1 virus 63:67 Japanese encephalitis virus 41:67 Japanese encephalitis virus infection of human dendritic cells 41:102 DC-SIGN as an attachment factor mediates Japanese encephalitis virus infection of human dendritic cells via interaction with a single high-mannose residue of viral E glycoprotein. 26629951 5 48 theme JEV 1077:1079 arg1 infection 1087:1095 JEV early infection 1077:1095 JEV early infection 1077:1095 Our findings highlight the potential significance of DC-SIGN in JEV early infection, providing a basis for further understanding how JEV exploits DC-SIGN to gain access to dendritic cells. 26629951 0 49 theme E 164:164 arg1 glycoprotein 166:177 viral E glycoprotein 158:177 viral E glycoprotein 158:177 DC-SIGN as an attachment factor mediates Japanese encephalitis virus infection of human dendritic cells via interaction with a single high-mannose residue of viral E glycoprotein. 26629951 0 50 theme viral 158:162 arg1 glycoprotein 166:177 viral E glycoprotein 158:177 viral E glycoprotein 158:177 DC-SIGN as an attachment factor mediates Japanese encephalitis virus infection of human dendritic cells via interaction with a single high-mannose residue of viral E glycoprotein. 26629951 2 51 gly glycoprotein 520:531 arg1 glycoprotein 504:515 JEV envelope glycoprotein 491:515 JEV envelope glycoprotein (E glycoprotein) 491:532 In the current study, following the demonstration of JEV productive infection in DCs, we revealed that the interaction between JEV envelope glycoprotein (E glycoprotein) and DC-SIGN was important for such infection as evidenced by antibody neutralization and siRNA knockdown experiments. 26629951 2 51 gly glycoprotein 520:531 arg1 glycoprotein 520:531 E glycoprotein 518:531 E glycoprotein 518:531 In the current study, following the demonstration of JEV productive infection in DCs, we revealed that the interaction between JEV envelope glycoprotein (E glycoprotein) and DC-SIGN was important for such infection as evidenced by antibody neutralization and siRNA knockdown experiments. 26629951 5 52 from significance 1050:1061 arg1 infection 1087:1095 JEV early infection 1077:1095 JEV early infection 1077:1095 Our findings highlight the potential significance of DC-SIGN in JEV early infection, providing a basis for further understanding how JEV exploits DC-SIGN to gain access to dendritic cells. 26629951 5 53 theme dendritic 1185:1193 arg1 cells 1195:1199 dendritic cells 1185:1199 dendritic cells 1185:1199 Our findings highlight the potential significance of DC-SIGN in JEV early infection, providing a basis for further understanding how JEV exploits DC-SIGN to gain access to dendritic cells. 26629951 2 54 gly glycoprotein 504:515 arg1 glycoprotein 504:515 JEV envelope glycoprotein 491:515 JEV envelope glycoprotein (E glycoprotein) 491:532 In the current study, following the demonstration of JEV productive infection in DCs, we revealed that the interaction between JEV envelope glycoprotein (E glycoprotein) and DC-SIGN was important for such infection as evidenced by antibody neutralization and siRNA knockdown experiments. 26629951 2 54 gly glycoprotein 504:515 arg1 glycoprotein 520:531 E glycoprotein 518:531 E glycoprotein 518:531 In the current study, following the demonstration of JEV productive infection in DCs, we revealed that the interaction between JEV envelope glycoprotein (E glycoprotein) and DC-SIGN was important for such infection as evidenced by antibody neutralization and siRNA knockdown experiments. 26629951 0 55 theme virus 63:67 arg1 infection 69:77 Japanese encephalitis virus infection 41:77 Japanese encephalitis virus infection of human dendritic cells 41:102 DC-SIGN as an attachment factor mediates Japanese encephalitis virus infection of human dendritic cells via interaction with a single high-mannose residue of viral E glycoprotein. 26629951 5 56 theme early 1081:1085 arg1 infection 1087:1095 JEV early infection 1077:1095 JEV early infection 1077:1095 Our findings highlight the potential significance of DC-SIGN in JEV early infection, providing a basis for further understanding how JEV exploits DC-SIGN to gain access to dendritic cells. 26629951 4 57 theme attachment 956:965 arg1 factor 967:972 an attachment factor 953:972 an attachment factor rather than an entry receptor for JEV 953:1010 These data together suggest that DC-SIGN functions as an attachment factor rather than an entry receptor for JEV. 26629951 4 57 theme attachment 956:965 arg1 DC-SIGN 932:938 DC-SIGN 932:938 DC-SIGN 932:938 These data together suggest that DC-SIGN functions as an attachment factor rather than an entry receptor for JEV. 26629951 3 58 theme motif 846:850 arg1 mutation 810:817 mutation 810:817 mutation of DC-SIGN internalization motif 810:850 Moreover, the high-mannose N-linked glycan at N154 of E glycoprotein was shown to be crucial for JEV binding to DC-SIGN and subsequent internalization, while mutation of DC-SIGN internalization motif did not affect JEV uptake and internalization. 26629951 3 59 theme JEV 749:751 arg1 binding 753:759 JEV binding 749:759 JEV binding to DC-SIGN 749:770 Moreover, the high-mannose N-linked glycan at N154 of E glycoprotein was shown to be crucial for JEV binding to DC-SIGN and subsequent internalization, while mutation of DC-SIGN internalization motif did not affect JEV uptake and internalization. 26611826 2 0 with U0317 404:408 arg1 homologies 415:424 homologies 415:424 homologies to the polysaccharide biosynthesis protein CapD 415:472 In the present study, we identified a gene in Enterococcus faecium U0317 with homologies to the polysaccharide biosynthesis protein CapD that is made up of 336 amino acids and putatively catalyzes N-linked glycosylation. 26611826 3 1 theme deletion 565:572 arg1 mutant 574:579 A capD deletion mutant 558:579 A capD deletion mutant 558:579 A capD deletion mutant was constructed and complemented by homologous recombination that was confirmed by PCR and sequencing. 26611826 7 2 theme mutant 1361:1366 arg1 colonization 1368:1379 mutant colonization 1361:1379 mutant colonization 1361:1379 By comparison more than 2-fold decrease was seen in mutant colonization and adherence to both T24 and Caco2 cells. 26611826 4 3 theme reconstituted 892:904 arg1 mutant 906:911 the reconstituted mutant 888:911 the reconstituted mutant 888:911 The mutant revealed different growth behavior and morphological changes compared to wild-type by scanning electron microscopy, also the capD mutant showed a strong hydrophobicity and that was reversed in the reconstituted mutant. 26611826 6 4 theme knock-out 1211:1219 arg1 mutant 1221:1226 the capD knock-out mutant 1202:1226 the capD knock-out mutant 1202:1226 Antibodies directed against alpha lipotechoic acid (αLTA) and the peptidyl-prolyl cis-trans isomerase (αPpiC), effectively mediated the opsonophagocytic killing in the capD knock-out mutant, while this activity was not observed in the wild-type and reconstituted mutant. 26611826 4 5 theme different 704:712 arg1 behavior 721:728 different growth behavior 704:728 different growth behavior 704:728 The mutant revealed different growth behavior and morphological changes compared to wild-type by scanning electron microscopy, also the capD mutant showed a strong hydrophobicity and that was reversed in the reconstituted mutant. 26611826 1 6 theme disease 212:218 arg1 pathogenesis 220:231 disease pathogenesis 212:231 disease pathogenesis 212:231 Most bacterial species produce capsular polysaccharides that contribute to disease pathogenesis through evasion of the host innate immune system and are also involved in inhibiting leukocyte killing. 26611826 9 7 from polysaccharide 1708:1721 arg1 pathogenesis 1782:1793 the disease pathogenesis 1770:1793 the disease pathogenesis 1770:1793 Further studies are needed to elucidate the function of capsular polysaccharide synthesis gene clusters and its involvement in the disease pathogenesis with the aim to develop targeted therapies to treat multidrug-resistant E. faecium infections. 26611826 9 8 theme synthesis 1723:1731 arg1 clusters 1738:1745 synthesis gene clusters 1723:1745 synthesis gene clusters 1723:1745 Further studies are needed to elucidate the function of capsular polysaccharide synthesis gene clusters and its involvement in the disease pathogenesis with the aim to develop targeted therapies to treat multidrug-resistant E. faecium infections. 26611826 2 9 from gene 375:378 arg1 U0317 404:408 Enterococcus faecium U0317 383:408 Enterococcus faecium U0317 with homologies to the polysaccharide biosynthesis protein CapD 383:472 In the present study, we identified a gene in Enterococcus faecium U0317 with homologies to the polysaccharide biosynthesis protein CapD that is made up of 336 amino acids and putatively catalyzes N-linked glycosylation. 26611826 9 10 with involvement 1755:1765 arg1 aim 1804:1806 the aim to develop targeted therapies to treat multidrug-resistant E. faecium infections 1800:1887 the aim to develop targeted therapies to treat multidrug-resistant E. faecium infections 1800:1887 Further studies are needed to elucidate the function of capsular polysaccharide synthesis gene clusters and its involvement in the disease pathogenesis with the aim to develop targeted therapies to treat multidrug-resistant E. faecium infections. 26611826 7 11 theme Caco2 1411:1415 arg1 cells 1417:1421 Caco2 cells 1411:1421 Caco2 cells 1411:1421 By comparison more than 2-fold decrease was seen in mutant colonization and adherence to both T24 and Caco2 cells. 26611826 5 12 theme in-vitro 968:975 arg1 culture 982:988 in-vitro cell culture 968:988 in-vitro cell culture 968:988 For further characterization and functional analyses, in-vitro cell culture and in-vivo a mouse infection models were used. 26611826 1 13 theme bacterial 142:150 arg1 species 152:158 Most bacterial species 137:158 Most bacterial species 137:158 Most bacterial species produce capsular polysaccharides that contribute to disease pathogenesis through evasion of the host innate immune system and are also involved in inhibiting leukocyte killing. 26611826 1 14 theme Most 137:140 arg1 species 152:158 Most bacterial species 137:158 Most bacterial species 137:158 Most bacterial species produce capsular polysaccharides that contribute to disease pathogenesis through evasion of the host innate immune system and are also involved in inhibiting leukocyte killing. 26611826 9 15 theme disease 1774:1780 arg1 pathogenesis 1782:1793 the disease pathogenesis 1770:1793 the disease pathogenesis 1770:1793 Further studies are needed to elucidate the function of capsular polysaccharide synthesis gene clusters and its involvement in the disease pathogenesis with the aim to develop targeted therapies to treat multidrug-resistant E. faecium infections. 26611826 5 16 used used 1032:1035 arg2 culture 982:988 in-vitro cell culture 968:988 in-vitro cell culture 968:988 For further characterization and functional analyses, in-vitro cell culture and in-vivo a mouse infection models were used. 26611826 5 16 used used 1032:1035 arg2 a 1002:1002 in-vivo a 994:1002 in-vivo a 994:1002 For further characterization and functional analyses, in-vitro cell culture and in-vivo a mouse infection models were used. 26611826 0 17 theme biosynthesis 78:89 arg1 CapD 100:103 CapD 100:103 CapD 100:103 Identification and functional characterization of the putative polysaccharide biosynthesis protein (CapD) of Enterococcus faecium U0317. 26611826 0 17 theme biosynthesis 78:89 arg1 protein 91:97 the putative polysaccharide biosynthesis protein 50:97 the putative polysaccharide biosynthesis protein (CapD) of Enterococcus faecium U0317 50:134 Identification and functional characterization of the putative polysaccharide biosynthesis protein (CapD) of Enterococcus faecium U0317. 26611826 2 18 theme biosynthesis 448:459 arg1 CapD 469:472 the polysaccharide biosynthesis protein CapD 429:472 the polysaccharide biosynthesis protein CapD 429:472 In the present study, we identified a gene in Enterococcus faecium U0317 with homologies to the polysaccharide biosynthesis protein CapD that is made up of 336 amino acids and putatively catalyzes N-linked glycosylation. 26611826 8 19 dep significant 1435:1445 arg1 higher 1447:1452 higher 1447:1452 higher 1447:1452 However, a significant higher bacterial colonization was observed in capD mutant during bacteremia in the animal model, while virulence in a mouse UTI (urinary tract infection) model, there were no obvious differences. 26611826 6 20 theme alpha 1066:1070 arg1 αLTA 1090:1093 αLTA 1090:1093 αLTA 1090:1093 Antibodies directed against alpha lipotechoic acid (αLTA) and the peptidyl-prolyl cis-trans isomerase (αPpiC), effectively mediated the opsonophagocytic killing in the capD knock-out mutant, while this activity was not observed in the wild-type and reconstituted mutant. 26611826 6 20 theme alpha 1066:1070 arg1 acid 1084:1087 alpha lipotechoic acid 1066:1087 alpha lipotechoic acid (αLTA) 1066:1094 Antibodies directed against alpha lipotechoic acid (αLTA) and the peptidyl-prolyl cis-trans isomerase (αPpiC), effectively mediated the opsonophagocytic killing in the capD knock-out mutant, while this activity was not observed in the wild-type and reconstituted mutant. 26611826 2 21 theme amino 497:501 arg1 acids 503:507 336 amino acids 493:507 336 amino acids 493:507 In the present study, we identified a gene in Enterococcus faecium U0317 with homologies to the polysaccharide biosynthesis protein CapD that is made up of 336 amino acids and putatively catalyzes N-linked glycosylation. 26611826 2 22 link N-linked 534:541 arg1 glycosylation 543:555 N-linked glycosylation 534:555 N-linked glycosylation 534:555 In the present study, we identified a gene in Enterococcus faecium U0317 with homologies to the polysaccharide biosynthesis protein CapD that is made up of 336 amino acids and putatively catalyzes N-linked glycosylation. 26611826 4 23 theme morphological 734:746 arg1 changes 748:754 morphological changes 734:754 morphological changes 734:754 The mutant revealed different growth behavior and morphological changes compared to wild-type by scanning electron microscopy, also the capD mutant showed a strong hydrophobicity and that was reversed in the reconstituted mutant. 26611826 4 24 theme capD 820:823 arg1 mutant 825:830 the capD mutant 816:830 the capD mutant 816:830 The mutant revealed different growth behavior and morphological changes compared to wild-type by scanning electron microscopy, also the capD mutant showed a strong hydrophobicity and that was reversed in the reconstituted mutant. 26611826 0 25 theme Enterococcus 109:120 arg1 faecium 122:128 Enterococcus faecium U0317 109:134 Enterococcus faecium U0317 109:134 Identification and functional characterization of the putative polysaccharide biosynthesis protein (CapD) of Enterococcus faecium U0317. 26611826 7 26 dep 2-fold 1333:1338 arg1 more 1323:1326 more 1323:1326 more 1323:1326 By comparison more than 2-fold decrease was seen in mutant colonization and adherence to both T24 and Caco2 cells. 26611826 7 26 dep 2-fold 1333:1338 arg1 than 1328:1331 than 1328:1331 than 1328:1331 By comparison more than 2-fold decrease was seen in mutant colonization and adherence to both T24 and Caco2 cells. 26611826 8 27 theme mouse 1565:1569 arg1 model 1601:1605 a mouse UTI (urinary tract infection) model 1563:1605 a mouse UTI (urinary tract infection) model 1563:1605 However, a significant higher bacterial colonization was observed in capD mutant during bacteremia in the animal model, while virulence in a mouse UTI (urinary tract infection) model, there were no obvious differences. 26611826 4 28 theme scanning 781:788 arg1 microscopy 799:808 scanning electron microscopy 781:808 scanning electron microscopy 781:808 The mutant revealed different growth behavior and morphological changes compared to wild-type by scanning electron microscopy, also the capD mutant showed a strong hydrophobicity and that was reversed in the reconstituted mutant. 26611826 5 29 theme in-vivo 994:1000 arg1 a 1002:1002 in-vivo a 994:1002 in-vivo a 994:1002 For further characterization and functional analyses, in-vitro cell culture and in-vivo a mouse infection models were used. 26611826 6 30 theme peptidyl-prolyl 1104:1118 arg1 αPpiC 1141:1145 αPpiC 1141:1145 αPpiC 1141:1145 Antibodies directed against alpha lipotechoic acid (αLTA) and the peptidyl-prolyl cis-trans isomerase (αPpiC), effectively mediated the opsonophagocytic killing in the capD knock-out mutant, while this activity was not observed in the wild-type and reconstituted mutant. 26611826 6 30 theme peptidyl-prolyl 1104:1118 arg1 isomerase 1130:1138 the peptidyl-prolyl cis-trans isomerase 1100:1138 the peptidyl-prolyl cis-trans isomerase (αPpiC) 1100:1146 Antibodies directed against alpha lipotechoic acid (αLTA) and the peptidyl-prolyl cis-trans isomerase (αPpiC), effectively mediated the opsonophagocytic killing in the capD knock-out mutant, while this activity was not observed in the wild-type and reconstituted mutant. 26611826 2 31 theme protein 461:467 arg1 CapD 469:472 the polysaccharide biosynthesis protein CapD 429:472 the polysaccharide biosynthesis protein CapD 429:472 In the present study, we identified a gene in Enterococcus faecium U0317 with homologies to the polysaccharide biosynthesis protein CapD that is made up of 336 amino acids and putatively catalyzes N-linked glycosylation. 26611826 6 32 located observed 1257:1264 arg2 activity 1240:1247 this activity 1235:1247 this activity 1235:1247 Antibodies directed against alpha lipotechoic acid (αLTA) and the peptidyl-prolyl cis-trans isomerase (αPpiC), effectively mediated the opsonophagocytic killing in the capD knock-out mutant, while this activity was not observed in the wild-type and reconstituted mutant. 26611826 6 32 located observed 1257:1264 arg1 wild-type 1273:1281 wild-type 1273:1281 wild-type 1273:1281 Antibodies directed against alpha lipotechoic acid (αLTA) and the peptidyl-prolyl cis-trans isomerase (αPpiC), effectively mediated the opsonophagocytic killing in the capD knock-out mutant, while this activity was not observed in the wild-type and reconstituted mutant. 26611826 6 32 located observed 1257:1264 arg1 mutant 1301:1306 mutant 1301:1306 mutant 1301:1306 Antibodies directed against alpha lipotechoic acid (αLTA) and the peptidyl-prolyl cis-trans isomerase (αPpiC), effectively mediated the opsonophagocytic killing in the capD knock-out mutant, while this activity was not observed in the wild-type and reconstituted mutant. 26611826 2 33 theme polysaccharide 433:446 arg1 CapD 469:472 the polysaccharide biosynthesis protein CapD 429:472 the polysaccharide biosynthesis protein CapD 429:472 In the present study, we identified a gene in Enterococcus faecium U0317 with homologies to the polysaccharide biosynthesis protein CapD that is made up of 336 amino acids and putatively catalyzes N-linked glycosylation. 26611826 0 34 theme functional 19:28 arg1 characterization 30:45 functional characterization 19:45 functional characterization 19:45 Identification and functional characterization of the putative polysaccharide biosynthesis protein (CapD) of Enterococcus faecium U0317. 26611826 5 35 theme mouse 1004:1008 arg1 models 1020:1025 mouse infection models 1004:1025 mouse infection models 1004:1025 For further characterization and functional analyses, in-vitro cell culture and in-vivo a mouse infection models were used. 26611826 9 36 theme E. 1867:1868 arg1 infections 1878:1887 multidrug-resistant E. faecium infections 1847:1887 multidrug-resistant E. faecium infections 1847:1887 Further studies are needed to elucidate the function of capsular polysaccharide synthesis gene clusters and its involvement in the disease pathogenesis with the aim to develop targeted therapies to treat multidrug-resistant E. faecium infections. 26611826 8 37 theme tract 1584:1588 arg1 infection 1590:1598 urinary tract infection 1576:1598 a mouse UTI (urinary tract infection) model 1563:1605 However, a significant higher bacterial colonization was observed in capD mutant during bacteremia in the animal model, while virulence in a mouse UTI (urinary tract infection) model, there were no obvious differences. 26611826 9 38 dep polysaccharide 1708:1721 arg1 clusters 1738:1745 synthesis gene clusters 1723:1745 synthesis gene clusters 1723:1745 Further studies are needed to elucidate the function of capsular polysaccharide synthesis gene clusters and its involvement in the disease pathogenesis with the aim to develop targeted therapies to treat multidrug-resistant E. faecium infections. 26611826 0 39 theme putative 54:61 arg1 CapD 100:103 CapD 100:103 CapD 100:103 Identification and functional characterization of the putative polysaccharide biosynthesis protein (CapD) of Enterococcus faecium U0317. 26611826 0 39 theme putative 54:61 arg1 protein 91:97 the putative polysaccharide biosynthesis protein 50:97 the putative polysaccharide biosynthesis protein (CapD) of Enterococcus faecium U0317 50:134 Identification and functional characterization of the putative polysaccharide biosynthesis protein (CapD) of Enterococcus faecium U0317. 26611826 6 40 theme opsonophagocytic 1174:1189 arg1 killing 1191:1197 the opsonophagocytic killing 1170:1197 the opsonophagocytic killing in the capD knock-out mutant 1170:1226 Antibodies directed against alpha lipotechoic acid (αLTA) and the peptidyl-prolyl cis-trans isomerase (αPpiC), effectively mediated the opsonophagocytic killing in the capD knock-out mutant, while this activity was not observed in the wild-type and reconstituted mutant. 26611826 9 41 theme Further 1643:1649 arg1 studies 1651:1657 Further studies 1643:1657 Further studies 1643:1657 Further studies are needed to elucidate the function of capsular polysaccharide synthesis gene clusters and its involvement in the disease pathogenesis with the aim to develop targeted therapies to treat multidrug-resistant E. faecium infections. 26611826 4 42 theme strong 841:846 arg1 hydrophobicity 848:861 a strong hydrophobicity 839:861 a strong hydrophobicity and that was reversed in the reconstituted mutant 839:911 The mutant revealed different growth behavior and morphological changes compared to wild-type by scanning electron microscopy, also the capD mutant showed a strong hydrophobicity and that was reversed in the reconstituted mutant. 26611826 1 43 theme innate 261:266 arg1 system 275:280 the host innate immune system 252:280 the host innate immune system 252:280 Most bacterial species produce capsular polysaccharides that contribute to disease pathogenesis through evasion of the host innate immune system and are also involved in inhibiting leukocyte killing. 26611826 9 44 from involvement 1755:1765 arg1 pathogenesis 1782:1793 the disease pathogenesis 1770:1793 the disease pathogenesis 1770:1793 Further studies are needed to elucidate the function of capsular polysaccharide synthesis gene clusters and its involvement in the disease pathogenesis with the aim to develop targeted therapies to treat multidrug-resistant E. faecium infections. 26611826 8 45 theme obvious 1622:1628 arg1 differences 1630:1640 no obvious differences 1619:1640 no obvious differences 1619:1640 However, a significant higher bacterial colonization was observed in capD mutant during bacteremia in the animal model, while virulence in a mouse UTI (urinary tract infection) model, there were no obvious differences. 26611826 1 46 theme system 275:280 arg1 evasion 241:247 evasion 241:247 evasion of the host innate immune system 241:280 Most bacterial species produce capsular polysaccharides that contribute to disease pathogenesis through evasion of the host innate immune system and are also involved in inhibiting leukocyte killing. 26611826 9 47 theme capsular 1699:1706 arg1 polysaccharide 1708:1721 capsular polysaccharide synthesis gene clusters and its involvement in the disease pathogenesis with the aim to develop targeted therapies to treat multidrug-resistant E. faecium infections 1699:1887 polysaccharide 1708:1721 Further studies are needed to elucidate the function of capsular polysaccharide synthesis gene clusters and its involvement in the disease pathogenesis with the aim to develop targeted therapies to treat multidrug-resistant E. faecium infections. 26611826 3 48 theme capD 560:563 arg1 mutant 574:579 A capD deletion mutant 558:579 A capD deletion mutant 558:579 A capD deletion mutant was constructed and complemented by homologous recombination that was confirmed by PCR and sequencing. 26611826 5 49 theme functional 947:956 arg1 analyses 958:965 functional analyses 947:965 functional analyses 947:965 For further characterization and functional analyses, in-vitro cell culture and in-vivo a mouse infection models were used. 26611826 9 50 dep E. 1867:1868 arg1 faecium 1870:1876 faecium 1870:1876 faecium 1870:1876 Further studies are needed to elucidate the function of capsular polysaccharide synthesis gene clusters and its involvement in the disease pathogenesis with the aim to develop targeted therapies to treat multidrug-resistant E. faecium infections. 26611826 9 51 theme polysaccharide 1708:1721 arg1 function 1687:1694 the function 1683:1694 the function of capsular polysaccharide synthesis gene clusters and its involvement in the disease pathogenesis with the aim to develop targeted therapies to treat multidrug-resistant E. faecium infections 1683:1887 Further studies are needed to elucidate the function of capsular polysaccharide synthesis gene clusters and its involvement in the disease pathogenesis with the aim to develop targeted therapies to treat multidrug-resistant E. faecium infections. 26611826 6 52 theme capD 1206:1209 arg1 mutant 1221:1226 the capD knock-out mutant 1202:1226 the capD knock-out mutant 1202:1226 Antibodies directed against alpha lipotechoic acid (αLTA) and the peptidyl-prolyl cis-trans isomerase (αPpiC), effectively mediated the opsonophagocytic killing in the capD knock-out mutant, while this activity was not observed in the wild-type and reconstituted mutant. 26611826 9 53 from function 1687:1694 arg1 pathogenesis 1782:1793 the disease pathogenesis 1770:1793 the disease pathogenesis 1770:1793 Further studies are needed to elucidate the function of capsular polysaccharide synthesis gene clusters and its involvement in the disease pathogenesis with the aim to develop targeted therapies to treat multidrug-resistant E. faecium infections. 26611826 9 54 theme gene 1733:1736 arg1 clusters 1738:1745 synthesis gene clusters 1723:1745 synthesis gene clusters 1723:1745 Further studies are needed to elucidate the function of capsular polysaccharide synthesis gene clusters and its involvement in the disease pathogenesis with the aim to develop targeted therapies to treat multidrug-resistant E. faecium infections. 26611826 8 55 theme capD 1493:1496 arg1 mutant 1498:1503 capD mutant 1493:1503 capD mutant 1493:1503 However, a significant higher bacterial colonization was observed in capD mutant during bacteremia in the animal model, while virulence in a mouse UTI (urinary tract infection) model, there were no obvious differences. 26611826 7 56 theme 2-fold 1333:1338 arg1 decrease 1340:1347 more than 2-fold decrease 1323:1347 more than 2-fold decrease 1323:1347 By comparison more than 2-fold decrease was seen in mutant colonization and adherence to both T24 and Caco2 cells. 26611826 3 57 theme homologous 617:626 arg1 recombination 628:640 homologous recombination 617:640 homologous recombination that was confirmed by PCR and sequencing 617:681 A capD deletion mutant was constructed and complemented by homologous recombination that was confirmed by PCR and sequencing. 26611826 5 58 theme further 918:924 arg1 characterization 926:941 further characterization 918:941 further characterization 918:941 For further characterization and functional analyses, in-vitro cell culture and in-vivo a mouse infection models were used. 26611826 8 59 located observed 1481:1488 arg1 mutant 1498:1503 capD mutant 1493:1503 capD mutant 1493:1503 However, a significant higher bacterial colonization was observed in capD mutant during bacteremia in the animal model, while virulence in a mouse UTI (urinary tract infection) model, there were no obvious differences. 26611826 8 59 located observed 1481:1488 arg1 model 1537:1541 the animal model 1526:1541 the animal model 1526:1541 However, a significant higher bacterial colonization was observed in capD mutant during bacteremia in the animal model, while virulence in a mouse UTI (urinary tract infection) model, there were no obvious differences. 26611826 8 59 located observed 1481:1488 arg2 colonization 1464:1475 a significant higher bacterial colonization 1433:1475 a significant higher bacterial colonization 1433:1475 However, a significant higher bacterial colonization was observed in capD mutant during bacteremia in the animal model, while virulence in a mouse UTI (urinary tract infection) model, there were no obvious differences. 26611826 9 60 theme involvement 1755:1765 arg1 function 1687:1694 the function 1683:1694 the function of capsular polysaccharide synthesis gene clusters and its involvement in the disease pathogenesis with the aim to develop targeted therapies to treat multidrug-resistant E. faecium infections 1683:1887 Further studies are needed to elucidate the function of capsular polysaccharide synthesis gene clusters and its involvement in the disease pathogenesis with the aim to develop targeted therapies to treat multidrug-resistant E. faecium infections. 26611826 5 61 theme cell 977:980 arg1 culture 982:988 in-vitro cell culture 968:988 in-vitro cell culture 968:988 For further characterization and functional analyses, in-vitro cell culture and in-vivo a mouse infection models were used. 26611826 8 62 theme animal 1530:1535 arg1 model 1537:1541 the animal model 1526:1541 the animal model 1526:1541 However, a significant higher bacterial colonization was observed in capD mutant during bacteremia in the animal model, while virulence in a mouse UTI (urinary tract infection) model, there were no obvious differences. 26611826 0 63 theme protein 91:97 arg1 Identification 0:13 Identification 0:13 Identification 0:13 Identification and functional characterization of the putative polysaccharide biosynthesis protein (CapD) of Enterococcus faecium U0317. 26611826 0 63 theme protein 91:97 arg1 characterization 30:45 functional characterization 19:45 functional characterization 19:45 Identification and functional characterization of the putative polysaccharide biosynthesis protein (CapD) of Enterococcus faecium U0317. 26611826 6 64 theme lipotechoic 1072:1082 arg1 αLTA 1090:1093 αLTA 1090:1093 αLTA 1090:1093 Antibodies directed against alpha lipotechoic acid (αLTA) and the peptidyl-prolyl cis-trans isomerase (αPpiC), effectively mediated the opsonophagocytic killing in the capD knock-out mutant, while this activity was not observed in the wild-type and reconstituted mutant. 26611826 6 64 theme lipotechoic 1072:1082 arg1 acid 1084:1087 alpha lipotechoic acid 1066:1087 alpha lipotechoic acid (αLTA) 1066:1094 Antibodies directed against alpha lipotechoic acid (αLTA) and the peptidyl-prolyl cis-trans isomerase (αPpiC), effectively mediated the opsonophagocytic killing in the capD knock-out mutant, while this activity was not observed in the wild-type and reconstituted mutant. 26611826 4 65 theme growth 714:719 arg1 behavior 721:728 different growth behavior 704:728 different growth behavior 704:728 The mutant revealed different growth behavior and morphological changes compared to wild-type by scanning electron microscopy, also the capD mutant showed a strong hydrophobicity and that was reversed in the reconstituted mutant. 26611826 1 66 theme capsular 168:175 arg1 polysaccharides 177:191 capsular polysaccharides 168:191 capsular polysaccharides that contribute to disease pathogenesis through evasion of the host innate immune system and are also involved in inhibiting leukocyte killing 168:334 Most bacterial species produce capsular polysaccharides that contribute to disease pathogenesis through evasion of the host innate immune system and are also involved in inhibiting leukocyte killing. 26611826 2 67 dep Enterococcus 383:394 arg1 faecium 396:402 faecium 396:402 faecium 396:402 In the present study, we identified a gene in Enterococcus faecium U0317 with homologies to the polysaccharide biosynthesis protein CapD that is made up of 336 amino acids and putatively catalyzes N-linked glycosylation. 26611826 5 68 theme infection 1010:1018 arg1 models 1020:1025 mouse infection models 1004:1025 mouse infection models 1004:1025 For further characterization and functional analyses, in-vitro cell culture and in-vivo a mouse infection models were used. 26611826 2 69 theme N-linked 534:541 arg1 glycosylation 543:555 N-linked glycosylation 534:555 N-linked glycosylation 534:555 In the present study, we identified a gene in Enterococcus faecium U0317 with homologies to the polysaccharide biosynthesis protein CapD that is made up of 336 amino acids and putatively catalyzes N-linked glycosylation. 26611826 5 70 dep culture 982:988 arg1 models 1020:1025 mouse infection models 1004:1025 mouse infection models 1004:1025 For further characterization and functional analyses, in-vitro cell culture and in-vivo a mouse infection models were used. 26611826 0 71 theme faecium 122:128 arg1 CapD 100:103 CapD 100:103 CapD 100:103 Identification and functional characterization of the putative polysaccharide biosynthesis protein (CapD) of Enterococcus faecium U0317. 26611826 0 71 theme faecium 122:128 arg1 protein 91:97 the putative polysaccharide biosynthesis protein 50:97 the putative polysaccharide biosynthesis protein (CapD) of Enterococcus faecium U0317 50:134 Identification and functional characterization of the putative polysaccharide biosynthesis protein (CapD) of Enterococcus faecium U0317. 26611826 9 72 theme targeted 1819:1826 arg1 therapies 1828:1836 targeted therapies 1819:1836 targeted therapies 1819:1836 Further studies are needed to elucidate the function of capsular polysaccharide synthesis gene clusters and its involvement in the disease pathogenesis with the aim to develop targeted therapies to treat multidrug-resistant E. faecium infections. 26611826 8 73 theme UTI 1571:1573 arg1 model 1601:1605 a mouse UTI (urinary tract infection) model 1563:1605 a mouse UTI (urinary tract infection) model 1563:1605 However, a significant higher bacterial colonization was observed in capD mutant during bacteremia in the animal model, while virulence in a mouse UTI (urinary tract infection) model, there were no obvious differences. 26611826 8 74 from virulence 1550:1558 arg1 model 1601:1605 a mouse UTI (urinary tract infection) model 1563:1605 a mouse UTI (urinary tract infection) model 1563:1605 However, a significant higher bacterial colonization was observed in capD mutant during bacteremia in the animal model, while virulence in a mouse UTI (urinary tract infection) model, there were no obvious differences. 26611826 6 75 theme cis-trans 1120:1128 arg1 αPpiC 1141:1145 αPpiC 1141:1145 αPpiC 1141:1145 Antibodies directed against alpha lipotechoic acid (αLTA) and the peptidyl-prolyl cis-trans isomerase (αPpiC), effectively mediated the opsonophagocytic killing in the capD knock-out mutant, while this activity was not observed in the wild-type and reconstituted mutant. 26611826 6 75 theme cis-trans 1120:1128 arg1 isomerase 1130:1138 the peptidyl-prolyl cis-trans isomerase 1100:1138 the peptidyl-prolyl cis-trans isomerase (αPpiC) 1100:1146 Antibodies directed against alpha lipotechoic acid (αLTA) and the peptidyl-prolyl cis-trans isomerase (αPpiC), effectively mediated the opsonophagocytic killing in the capD knock-out mutant, while this activity was not observed in the wild-type and reconstituted mutant. 26611826 8 76 theme urinary 1576:1582 arg1 infection 1590:1598 urinary tract infection 1576:1598 a mouse UTI (urinary tract infection) model 1563:1605 However, a significant higher bacterial colonization was observed in capD mutant during bacteremia in the animal model, while virulence in a mouse UTI (urinary tract infection) model, there were no obvious differences. 26611826 2 77 theme Enterococcus 383:394 arg1 U0317 404:408 Enterococcus faecium U0317 383:408 Enterococcus faecium U0317 with homologies to the polysaccharide biosynthesis protein CapD 383:472 In the present study, we identified a gene in Enterococcus faecium U0317 with homologies to the polysaccharide biosynthesis protein CapD that is made up of 336 amino acids and putatively catalyzes N-linked glycosylation. 26611826 9 78 theme multidrug-resistant 1847:1865 arg1 infections 1878:1887 multidrug-resistant E. faecium infections 1847:1887 multidrug-resistant E. faecium infections 1847:1887 Further studies are needed to elucidate the function of capsular polysaccharide synthesis gene clusters and its involvement in the disease pathogenesis with the aim to develop targeted therapies to treat multidrug-resistant E. faecium infections. 26611826 8 79 theme infection 1590:1598 arg1 model 1601:1605 a mouse UTI (urinary tract infection) model 1563:1605 a mouse UTI (urinary tract infection) model 1563:1605 However, a significant higher bacterial colonization was observed in capD mutant during bacteremia in the animal model, while virulence in a mouse UTI (urinary tract infection) model, there were no obvious differences. 26611826 4 80 theme electron 790:797 arg1 microscopy 799:808 scanning electron microscopy 781:808 scanning electron microscopy 781:808 The mutant revealed different growth behavior and morphological changes compared to wild-type by scanning electron microscopy, also the capD mutant showed a strong hydrophobicity and that was reversed in the reconstituted mutant. 26611826 1 81 theme leukocyte 318:326 arg1 killing 328:334 leukocyte killing 318:334 leukocyte killing 318:334 Most bacterial species produce capsular polysaccharides that contribute to disease pathogenesis through evasion of the host innate immune system and are also involved in inhibiting leukocyte killing. 26611826 0 82 theme polysaccharide 63:76 arg1 CapD 100:103 CapD 100:103 CapD 100:103 Identification and functional characterization of the putative polysaccharide biosynthesis protein (CapD) of Enterococcus faecium U0317. 26611826 0 82 theme polysaccharide 63:76 arg1 protein 91:97 the putative polysaccharide biosynthesis protein 50:97 the putative polysaccharide biosynthesis protein (CapD) of Enterococcus faecium U0317 50:134 Identification and functional characterization of the putative polysaccharide biosynthesis protein (CapD) of Enterococcus faecium U0317. 26611826 8 83 theme significant 1435:1445 arg1 colonization 1464:1475 a significant higher bacterial colonization 1433:1475 a significant higher bacterial colonization 1433:1475 However, a significant higher bacterial colonization was observed in capD mutant during bacteremia in the animal model, while virulence in a mouse UTI (urinary tract infection) model, there were no obvious differences. 26611826 6 84 from killing 1191:1197 arg1 mutant 1221:1226 the capD knock-out mutant 1202:1226 the capD knock-out mutant 1202:1226 Antibodies directed against alpha lipotechoic acid (αLTA) and the peptidyl-prolyl cis-trans isomerase (αPpiC), effectively mediated the opsonophagocytic killing in the capD knock-out mutant, while this activity was not observed in the wild-type and reconstituted mutant. 26611826 9 85 with polysaccharide 1708:1721 arg1 aim 1804:1806 the aim to develop targeted therapies to treat multidrug-resistant E. faecium infections 1800:1887 the aim to develop targeted therapies to treat multidrug-resistant E. faecium infections 1800:1887 Further studies are needed to elucidate the function of capsular polysaccharide synthesis gene clusters and its involvement in the disease pathogenesis with the aim to develop targeted therapies to treat multidrug-resistant E. faecium infections. 26611826 8 86 theme bacterial 1454:1462 arg1 colonization 1464:1475 a significant higher bacterial colonization 1433:1475 a significant higher bacterial colonization 1433:1475 However, a significant higher bacterial colonization was observed in capD mutant during bacteremia in the animal model, while virulence in a mouse UTI (urinary tract infection) model, there were no obvious differences. 26611826 2 87 theme present 344:350 arg1 study 352:356 the present study 340:356 the present study 340:356 In the present study, we identified a gene in Enterococcus faecium U0317 with homologies to the polysaccharide biosynthesis protein CapD that is made up of 336 amino acids and putatively catalyzes N-linked glycosylation. 26611826 1 88 theme host 256:259 arg1 system 275:280 the host innate immune system 252:280 the host innate immune system 252:280 Most bacterial species produce capsular polysaccharides that contribute to disease pathogenesis through evasion of the host innate immune system and are also involved in inhibiting leukocyte killing. 26611826 9 89 from pathogenesis 1782:1793 arg1 function 1687:1694 the function 1683:1694 the function of capsular polysaccharide synthesis gene clusters and its involvement in the disease pathogenesis with the aim to develop targeted therapies to treat multidrug-resistant E. faecium infections 1683:1887 Further studies are needed to elucidate the function of capsular polysaccharide synthesis gene clusters and its involvement in the disease pathogenesis with the aim to develop targeted therapies to treat multidrug-resistant E. faecium infections. 26611826 1 90 theme immune 268:273 arg1 system 275:280 the host innate immune system 252:280 the host innate immune system 252:280 Most bacterial species produce capsular polysaccharides that contribute to disease pathogenesis through evasion of the host innate immune system and are also involved in inhibiting leukocyte killing. 26244810 3 0 theme terminal 608:615 arg1 fucoses 617:623 abundant terminal fucoses 599:623 abundant terminal fucoses 599:623 In this study, the N-linked glycan mass spectrometry profile of wild-type mouse kidney glycoproteins revealed the presence of abundant terminal fucoses, which were lost following knockout of the Fut9 gene; the terminal fucose was therefore concluded to be Le(x). 26244810 7 1 gly glycopeptides 1352:1364 arg2 glycopeptides 1352:1364 the glycopeptides 1348:1364 the glycopeptides 1348:1364 The site-specific N-glycomes on the glycopeptides were subsequently analyzed by adopting a new glycoproteomic technology composed of dissociation-independent assignment of glycopeptide signals and accurate mass-based prediction of the N-glycome on the glycopeptides. 26244810 9 2 theme first 1545:1549 arg1 report 1551:1556 the first report 1541:1556 the first report of large-scale identification of Le(x)-carrying glycoproteins from a native sample based on the site-specific glycome analysis 1541:1683 This is the first report of large-scale identification of Le(x)-carrying glycoproteins from a native sample based on the site-specific glycome analysis. 26244810 9 2 theme first 1545:1549 arg1 This 1533:1536 This 1533:1536 This 1533:1536 This is the first report of large-scale identification of Le(x)-carrying glycoproteins from a native sample based on the site-specific glycome analysis. 26244810 6 3 theme kidney 1044:1049 arg1 homogenates 1051:1061 kidney homogenates 1044:1061 kidney homogenates of wild-type and Fut9 knockout mice 1044:1097 Glycopeptides carrying fucosylated glycans were collected by Aleuria aurantia lectin (AAL) affinity chromatography from kidney homogenates of wild-type and Fut9 knockout mice. 26244810 7 4 theme N-glycome 1335:1343 arg1 assignment 1258:1267 dissociation-independent assignment 1233:1267 dissociation-independent assignment of glycopeptide signals 1233:1291 The site-specific N-glycomes on the glycopeptides were subsequently analyzed by adopting a new glycoproteomic technology composed of dissociation-independent assignment of glycopeptide signals and accurate mass-based prediction of the N-glycome on the glycopeptides. 26244810 7 4 theme N-glycome 1335:1343 arg1 prediction 1317:1326 accurate mass-based prediction 1297:1326 accurate mass-based prediction of the N-glycome on the glycopeptides 1297:1364 The site-specific N-glycomes on the glycopeptides were subsequently analyzed by adopting a new glycoproteomic technology composed of dissociation-independent assignment of glycopeptide signals and accurate mass-based prediction of the N-glycome on the glycopeptides. 26244810 3 5 theme Fut9 668:671 arg1 gene 673:676 the Fut9 gene 664:676 the Fut9 gene 664:676 In this study, the N-linked glycan mass spectrometry profile of wild-type mouse kidney glycoproteins revealed the presence of abundant terminal fucoses, which were lost following knockout of the Fut9 gene; the terminal fucose was therefore concluded to be Le(x). 26244810 9 6 theme identification 1573:1586 arg1 report 1551:1556 the first report 1541:1556 the first report of large-scale identification of Le(x)-carrying glycoproteins from a native sample based on the site-specific glycome analysis 1541:1683 This is the first report of large-scale identification of Le(x)-carrying glycoproteins from a native sample based on the site-specific glycome analysis. 26244810 9 6 theme identification 1573:1586 arg1 This 1533:1536 This 1533:1536 This 1533:1536 This is the first report of large-scale identification of Le(x)-carrying glycoproteins from a native sample based on the site-specific glycome analysis. 26244810 7 7 theme accurate 1297:1304 arg1 prediction 1317:1326 accurate mass-based prediction 1297:1326 accurate mass-based prediction of the N-glycome on the glycopeptides 1297:1364 The site-specific N-glycomes on the glycopeptides were subsequently analyzed by adopting a new glycoproteomic technology composed of dissociation-independent assignment of glycopeptide signals and accurate mass-based prediction of the N-glycome on the glycopeptides. 26244810 9 8 gly glycoproteins 1606:1618 arg1 glycoproteins 1606:1618 Le(x)-carrying glycoproteins 1591:1618 Le(x)-carrying glycoproteins from a native sample based on the site-specific glycome analysis 1591:1683 This is the first report of large-scale identification of Le(x)-carrying glycoproteins from a native sample based on the site-specific glycome analysis. 26244810 9 9 theme Le 1591:1592 arg1 glycoproteins 1606:1618 Le(x)-carrying glycoproteins 1591:1618 Le(x)-carrying glycoproteins from a native sample based on the site-specific glycome analysis 1591:1683 This is the first report of large-scale identification of Le(x)-carrying glycoproteins from a native sample based on the site-specific glycome analysis. 26244810 7 10 theme mass-based 1306:1315 arg1 prediction 1317:1326 accurate mass-based prediction 1297:1326 accurate mass-based prediction of the N-glycome on the glycopeptides 1297:1364 The site-specific N-glycomes on the glycopeptides were subsequently analyzed by adopting a new glycoproteomic technology composed of dissociation-independent assignment of glycopeptide signals and accurate mass-based prediction of the N-glycome on the glycopeptides. 26244810 3 11 theme terminal 683:690 arg1 Le 729:730 Le 729:730 Le(x) 729:733 In this study, the N-linked glycan mass spectrometry profile of wild-type mouse kidney glycoproteins revealed the presence of abundant terminal fucoses, which were lost following knockout of the Fut9 gene; the terminal fucose was therefore concluded to be Le(x). 26244810 3 11 theme terminal 683:690 arg1 fucose 692:697 the terminal fucose 679:697 the terminal fucose 679:697 In this study, the N-linked glycan mass spectrometry profile of wild-type mouse kidney glycoproteins revealed the presence of abundant terminal fucoses, which were lost following knockout of the Fut9 gene; the terminal fucose was therefore concluded to be Le(x). 26244810 3 12 theme mass 508:511 arg1 profile 526:532 the N-linked glycan mass spectrometry profile 488:532 the N-linked glycan mass spectrometry profile of wild-type mouse kidney glycoproteins 488:572 In this study, the N-linked glycan mass spectrometry profile of wild-type mouse kidney glycoproteins revealed the presence of abundant terminal fucoses, which were lost following knockout of the Fut9 gene; the terminal fucose was therefore concluded to be Le(x). 26244810 3 13 theme N-linked 492:499 arg1 profile 526:532 the N-linked glycan mass spectrometry profile 488:532 the N-linked glycan mass spectrometry profile of wild-type mouse kidney glycoproteins 488:572 In this study, the N-linked glycan mass spectrometry profile of wild-type mouse kidney glycoproteins revealed the presence of abundant terminal fucoses, which were lost following knockout of the Fut9 gene; the terminal fucose was therefore concluded to be Le(x). 26244810 9 14 theme -carrying 1596:1604 arg1 glycoproteins 1606:1618 Le(x)-carrying glycoproteins 1591:1618 Le(x)-carrying glycoproteins from a native sample based on the site-specific glycome analysis 1591:1683 This is the first report of large-scale identification of Le(x)-carrying glycoproteins from a native sample based on the site-specific glycome analysis. 26244810 7 15 theme glycopeptide 1272:1283 arg1 signals 1285:1291 glycopeptide signals 1272:1291 glycopeptide signals 1272:1291 The site-specific N-glycomes on the glycopeptides were subsequently analyzed by adopting a new glycoproteomic technology composed of dissociation-independent assignment of glycopeptide signals and accurate mass-based prediction of the N-glycome on the glycopeptides. 26244810 6 16 theme knockout 1085:1092 arg1 mice 1094:1097 wild-type and Fut9 knockout mice 1066:1097 wild-type and Fut9 knockout mice 1066:1097 Glycopeptides carrying fucosylated glycans were collected by Aleuria aurantia lectin (AAL) affinity chromatography from kidney homogenates of wild-type and Fut9 knockout mice. 26244810 5 17 theme mouse 910:914 arg1 kidney 916:921 the mouse kidney 906:921 the mouse kidney 906:921 We endeavored to comprehensively identify the Le(x) carriers in the mouse kidney. 26244810 3 18 theme wild-type 537:545 arg1 glycoproteins 560:572 wild-type mouse kidney glycoproteins 537:572 wild-type mouse kidney glycoproteins 537:572 In this study, the N-linked glycan mass spectrometry profile of wild-type mouse kidney glycoproteins revealed the presence of abundant terminal fucoses, which were lost following knockout of the Fut9 gene; the terminal fucose was therefore concluded to be Le(x). 26244810 1 19 theme x 142:142 arg1 structure 152:160 The Lewis x (Le(x)) structure 132:160 The Lewis x (Le(x)) structure (Galβ1-4(Fucα1-3)GlcNAc-R) 132:187 The Lewis x (Le(x)) structure (Galβ1-4(Fucα1-3)GlcNAc-R) is a carbohydrate epitope comprising the stage-specific embryonic antigen-1 (SSEA-1) and CD15, and it is synthesized by α1,3-fucosyltransferase 9 (Fut9). 26244810 1 19 theme x 142:142 arg1 epitope 207:213 a carbohydrate epitope 192:213 a carbohydrate epitope comprising the stage-specific embryonic antigen-1 (SSEA-1) and CD15 192:281 The Lewis x (Le(x)) structure (Galβ1-4(Fucα1-3)GlcNAc-R) is a carbohydrate epitope comprising the stage-specific embryonic antigen-1 (SSEA-1) and CD15, and it is synthesized by α1,3-fucosyltransferase 9 (Fut9). 26244810 1 19 theme x 142:142 arg1 GlcNAc-R 179:186 Galβ1-4(Fucα1-3)GlcNAc-R 163:186 Galβ1-4(Fucα1-3)GlcNAc-R 163:186 The Lewis x (Le(x)) structure (Galβ1-4(Fucα1-3)GlcNAc-R) is a carbohydrate epitope comprising the stage-specific embryonic antigen-1 (SSEA-1) and CD15, and it is synthesized by α1,3-fucosyltransferase 9 (Fut9). 26244810 7 20 from N-glycome 1335:1343 arg1 glycopeptides 1352:1364 the glycopeptides 1348:1364 the glycopeptides 1348:1364 The site-specific N-glycomes on the glycopeptides were subsequently analyzed by adopting a new glycoproteomic technology composed of dissociation-independent assignment of glycopeptide signals and accurate mass-based prediction of the N-glycome on the glycopeptides. 26244810 6 21 contain carrying 938:945 arg1 Glycopeptides 924:936 Glycopeptides 924:936 Glycopeptides carrying fucosylated glycans 924:965 Glycopeptides carrying fucosylated glycans were collected by Aleuria aurantia lectin (AAL) affinity chromatography from kidney homogenates of wild-type and Fut9 knockout mice. 26244810 6 21 contain carrying 938:945 arg2 glycans 959:965 fucosylated glycans 947:965 fucosylated glycans 947:965 Glycopeptides carrying fucosylated glycans were collected by Aleuria aurantia lectin (AAL) affinity chromatography from kidney homogenates of wild-type and Fut9 knockout mice. 26244810 7 22 theme site-specific 1104:1116 arg1 N-glycomes 1118:1127 The site-specific N-glycomes 1100:1127 The site-specific N-glycomes on the glycopeptides 1100:1148 The site-specific N-glycomes on the glycopeptides were subsequently analyzed by adopting a new glycoproteomic technology composed of dissociation-independent assignment of glycopeptide signals and accurate mass-based prediction of the N-glycome on the glycopeptides. 26244810 9 23 theme native 1627:1632 arg1 sample 1634:1639 a native sample 1625:1639 a native sample based on the site-specific glycome analysis 1625:1683 This is the first report of large-scale identification of Le(x)-carrying glycoproteins from a native sample based on the site-specific glycome analysis. 26244810 0 24 theme N-Glycan 88:95 arg1 Alterations 97:107 Lewis x and Site-Specific N-Glycan Alterations 62:107 Lewis x and Site-Specific N-Glycan Alterations in Fut9 Knockout Mice 62:129 Large-Scale Identification of N-Glycan Glycoproteins Carrying Lewis x and Site-Specific N-Glycan Alterations in Fut9 Knockout Mice. 26244810 7 25 theme signals 1285:1291 arg1 assignment 1258:1267 dissociation-independent assignment 1233:1267 dissociation-independent assignment of glycopeptide signals 1233:1291 The site-specific N-glycomes on the glycopeptides were subsequently analyzed by adopting a new glycoproteomic technology composed of dissociation-independent assignment of glycopeptide signals and accurate mass-based prediction of the N-glycome on the glycopeptides. 26244810 7 25 theme signals 1285:1291 arg1 prediction 1317:1326 accurate mass-based prediction 1297:1326 accurate mass-based prediction of the N-glycome on the glycopeptides 1297:1364 The site-specific N-glycomes on the glycopeptides were subsequently analyzed by adopting a new glycoproteomic technology composed of dissociation-independent assignment of glycopeptide signals and accurate mass-based prediction of the N-glycome on the glycopeptides. 26244810 7 26 from assignment 1258:1267 arg1 glycopeptides 1352:1364 the glycopeptides 1348:1364 the glycopeptides 1348:1364 The site-specific N-glycomes on the glycopeptides were subsequently analyzed by adopting a new glycoproteomic technology composed of dissociation-independent assignment of glycopeptide signals and accurate mass-based prediction of the N-glycome on the glycopeptides. 26244810 0 27 theme Knockout 117:124 arg1 Mice 126:129 Fut9 Knockout Mice 112:129 Fut9 Knockout Mice 112:129 Large-Scale Identification of N-Glycan Glycoproteins Carrying Lewis x and Site-Specific N-Glycan Alterations in Fut9 Knockout Mice. 26244810 7 28 theme dissociation-independent 1233:1256 arg1 assignment 1258:1267 dissociation-independent assignment 1233:1267 dissociation-independent assignment of glycopeptide signals 1233:1291 The site-specific N-glycomes on the glycopeptides were subsequently analyzed by adopting a new glycoproteomic technology composed of dissociation-independent assignment of glycopeptide signals and accurate mass-based prediction of the N-glycome on the glycopeptides. 26244810 9 29 theme glycome 1668:1674 arg1 analysis 1676:1683 the site-specific glycome analysis 1650:1683 the site-specific glycome analysis 1650:1683 This is the first report of large-scale identification of Le(x)-carrying glycoproteins from a native sample based on the site-specific glycome analysis. 26244810 8 30 theme wild-type 1460:1468 arg1 kidney 1470:1475 wild-type kidney 1460:1475 wild-type kidney 1460:1475 Our analyses demonstrated that 24/32 glycoproteins contained the Le(x) N-glycan structure in wild-type kidney; of these, Le(x) was lost from 21 in the knockout mice. 26244810 0 31 theme Large-Scale 0:10 arg1 Identification 12:25 Large-Scale Identification 0:25 Large-Scale Identification of N-Glycan Glycoproteins 0:51 Large-Scale Identification of N-Glycan Glycoproteins Carrying Lewis x and Site-Specific N-Glycan Alterations in Fut9 Knockout Mice. 26244810 1 32 theme stage-specific 230:243 arg1 antigen-1 255:263 the stage-specific embryonic antigen-1 226:263 the stage-specific embryonic antigen-1 (SSEA-1) 226:272 The Lewis x (Le(x)) structure (Galβ1-4(Fucα1-3)GlcNAc-R) is a carbohydrate epitope comprising the stage-specific embryonic antigen-1 (SSEA-1) and CD15, and it is synthesized by α1,3-fucosyltransferase 9 (Fut9). 26244810 1 32 theme stage-specific 230:243 arg1 SSEA-1 266:271 SSEA-1 266:271 SSEA-1 266:271 The Lewis x (Le(x)) structure (Galβ1-4(Fucα1-3)GlcNAc-R) is a carbohydrate epitope comprising the stage-specific embryonic antigen-1 (SSEA-1) and CD15, and it is synthesized by α1,3-fucosyltransferase 9 (Fut9). 26244810 2 33 dep stomach 381:387 arg1 the 377:379 the 377:379 the 377:379 Fut9 is expressed specifically in the stomach, kidney, brain, and in leukocytes, suggesting a specific function in these tissues. 26244810 7 34 theme glycoproteomic 1195:1208 arg1 technology 1210:1219 a new glycoproteomic technology 1189:1219 a new glycoproteomic technology composed of dissociation-independent assignment of glycopeptide signals and accurate mass-based prediction of the N-glycome on the glycopeptides 1189:1364 The site-specific N-glycomes on the glycopeptides were subsequently analyzed by adopting a new glycoproteomic technology composed of dissociation-independent assignment of glycopeptide signals and accurate mass-based prediction of the N-glycome on the glycopeptides. 26244810 0 35 theme Glycoproteins 39:51 arg1 Identification 12:25 Large-Scale Identification 0:25 Large-Scale Identification of N-Glycan Glycoproteins 0:51 Large-Scale Identification of N-Glycan Glycoproteins Carrying Lewis x and Site-Specific N-Glycan Alterations in Fut9 Knockout Mice. 26244810 3 36 theme kidney 553:558 arg1 glycoproteins 560:572 wild-type mouse kidney glycoproteins 537:572 wild-type mouse kidney glycoproteins 537:572 In this study, the N-linked glycan mass spectrometry profile of wild-type mouse kidney glycoproteins revealed the presence of abundant terminal fucoses, which were lost following knockout of the Fut9 gene; the terminal fucose was therefore concluded to be Le(x). 26244810 0 37 theme Lewis 62:66 arg1 x 68:68 Lewis x 62:68 Lewis x 62:68 Large-Scale Identification of N-Glycan Glycoproteins Carrying Lewis x and Site-Specific N-Glycan Alterations in Fut9 Knockout Mice. 26244810 6 38 theme lectin 1002:1007 arg1 chromatography 1024:1037 Aleuria aurantia lectin (AAL) affinity chromatography 985:1037 Aleuria aurantia lectin (AAL) affinity chromatography 985:1037 Glycopeptides carrying fucosylated glycans were collected by Aleuria aurantia lectin (AAL) affinity chromatography from kidney homogenates of wild-type and Fut9 knockout mice. 26244810 3 39 theme abundant 599:606 arg1 fucoses 617:623 abundant terminal fucoses 599:623 abundant terminal fucoses 599:623 In this study, the N-linked glycan mass spectrometry profile of wild-type mouse kidney glycoproteins revealed the presence of abundant terminal fucoses, which were lost following knockout of the Fut9 gene; the terminal fucose was therefore concluded to be Le(x). 26244810 6 40 theme Aleuria 985:991 arg1 AAL 1010:1012 AAL 1010:1012 AAL 1010:1012 Glycopeptides carrying fucosylated glycans were collected by Aleuria aurantia lectin (AAL) affinity chromatography from kidney homogenates of wild-type and Fut9 knockout mice. 26244810 6 40 theme Aleuria 985:991 arg1 lectin 1002:1007 Aleuria aurantia lectin 985:1007 Aleuria aurantia lectin (AAL) affinity chromatography 985:1037 Glycopeptides carrying fucosylated glycans were collected by Aleuria aurantia lectin (AAL) affinity chromatography from kidney homogenates of wild-type and Fut9 knockout mice. 26244810 5 41 theme Le 888:889 arg1 carriers 894:901 the Le(x) carriers 884:901 the Le(x) carriers in the mouse kidney 884:921 We endeavored to comprehensively identify the Le(x) carriers in the mouse kidney. 26244810 1 42 theme carbohydrate 194:205 arg1 structure 152:160 The Lewis x (Le(x)) structure 132:160 The Lewis x (Le(x)) structure (Galβ1-4(Fucα1-3)GlcNAc-R) 132:187 The Lewis x (Le(x)) structure (Galβ1-4(Fucα1-3)GlcNAc-R) is a carbohydrate epitope comprising the stage-specific embryonic antigen-1 (SSEA-1) and CD15, and it is synthesized by α1,3-fucosyltransferase 9 (Fut9). 26244810 1 42 theme carbohydrate 194:205 arg1 epitope 207:213 a carbohydrate epitope 192:213 a carbohydrate epitope comprising the stage-specific embryonic antigen-1 (SSEA-1) and CD15 192:281 The Lewis x (Le(x)) structure (Galβ1-4(Fucα1-3)GlcNAc-R) is a carbohydrate epitope comprising the stage-specific embryonic antigen-1 (SSEA-1) and CD15, and it is synthesized by α1,3-fucosyltransferase 9 (Fut9). 26244810 7 43 from N-glycomes 1118:1127 arg1 glycopeptides 1136:1148 the glycopeptides 1132:1148 the glycopeptides 1132:1148 The site-specific N-glycomes on the glycopeptides were subsequently analyzed by adopting a new glycoproteomic technology composed of dissociation-independent assignment of glycopeptide signals and accurate mass-based prediction of the N-glycome on the glycopeptides. 26244810 3 44 gly glycoproteins 560:572 arg1 glycoproteins 560:572 wild-type mouse kidney glycoproteins 537:572 wild-type mouse kidney glycoproteins 537:572 In this study, the N-linked glycan mass spectrometry profile of wild-type mouse kidney glycoproteins revealed the presence of abundant terminal fucoses, which were lost following knockout of the Fut9 gene; the terminal fucose was therefore concluded to be Le(x). 26244810 3 45 theme fucoses 617:623 arg1 presence 587:594 the presence 583:594 the presence of abundant terminal fucoses, which were lost following knockout of the Fut9 gene 583:676 In this study, the N-linked glycan mass spectrometry profile of wild-type mouse kidney glycoproteins revealed the presence of abundant terminal fucoses, which were lost following knockout of the Fut9 gene; the terminal fucose was therefore concluded to be Le(x). 26244810 4 46 theme Le 765:766 arg1 presence 771:778 Le(x) presence 765:778 Le(x) presence 765:778 These results suggested that Le(x) presence is widespread rather than being limited to specific proteins. 26244810 8 47 theme knockout 1518:1525 arg1 mice 1527:1530 the knockout mice 1514:1530 the knockout mice 1514:1530 Our analyses demonstrated that 24/32 glycoproteins contained the Le(x) N-glycan structure in wild-type kidney; of these, Le(x) was lost from 21 in the knockout mice. 26244810 8 48 from structure 1447:1455 arg1 kidney 1470:1475 wild-type kidney 1460:1475 wild-type kidney 1460:1475 Our analyses demonstrated that 24/32 glycoproteins contained the Le(x) N-glycan structure in wild-type kidney; of these, Le(x) was lost from 21 in the knockout mice. 26244810 7 49 gly glycopeptide 1272:1283 arg2 glycopeptide 1272:1283 glycopeptide signals 1272:1291 glycopeptide signals 1272:1291 The site-specific N-glycomes on the glycopeptides were subsequently analyzed by adopting a new glycoproteomic technology composed of dissociation-independent assignment of glycopeptide signals and accurate mass-based prediction of the N-glycome on the glycopeptides. 26244810 9 50 theme large-scale 1561:1571 arg1 identification 1573:1586 large-scale identification 1561:1586 large-scale identification of Le(x)-carrying glycoproteins from a native sample based on the site-specific glycome analysis 1561:1683 This is the first report of large-scale identification of Le(x)-carrying glycoproteins from a native sample based on the site-specific glycome analysis. 26244810 6 51 theme affinity 1015:1022 arg1 chromatography 1024:1037 Aleuria aurantia lectin (AAL) affinity chromatography 985:1037 Aleuria aurantia lectin (AAL) affinity chromatography 985:1037 Glycopeptides carrying fucosylated glycans were collected by Aleuria aurantia lectin (AAL) affinity chromatography from kidney homogenates of wild-type and Fut9 knockout mice. 26244810 3 52 theme gene 673:676 arg1 knockout 652:659 knockout 652:659 knockout 652:659 In this study, the N-linked glycan mass spectrometry profile of wild-type mouse kidney glycoproteins revealed the presence of abundant terminal fucoses, which were lost following knockout of the Fut9 gene; the terminal fucose was therefore concluded to be Le(x). 26244810 5 53 from carriers 894:901 arg1 kidney 916:921 the mouse kidney 906:921 the mouse kidney 906:921 We endeavored to comprehensively identify the Le(x) carriers in the mouse kidney. 26244810 8 54 gly glycoproteins 1404:1416 arg1 glycoproteins 1404:1416 24/32 glycoproteins 1398:1416 24/32 glycoproteins 1398:1416 Our analyses demonstrated that 24/32 glycoproteins contained the Le(x) N-glycan structure in wild-type kidney; of these, Le(x) was lost from 21 in the knockout mice. 26244810 0 55 from Alterations 97:107 arg1 Mice 126:129 Fut9 Knockout Mice 112:129 Fut9 Knockout Mice 112:129 Large-Scale Identification of N-Glycan Glycoproteins Carrying Lewis x and Site-Specific N-Glycan Alterations in Fut9 Knockout Mice. 26244810 3 56 theme glycan 501:506 arg1 profile 526:532 the N-linked glycan mass spectrometry profile 488:532 the N-linked glycan mass spectrometry profile of wild-type mouse kidney glycoproteins 488:572 In this study, the N-linked glycan mass spectrometry profile of wild-type mouse kidney glycoproteins revealed the presence of abundant terminal fucoses, which were lost following knockout of the Fut9 gene; the terminal fucose was therefore concluded to be Le(x). 26244810 1 57 theme Fucα1-3 171:177 arg1 structure 152:160 The Lewis x (Le(x)) structure 132:160 The Lewis x (Le(x)) structure (Galβ1-4(Fucα1-3)GlcNAc-R) 132:187 The Lewis x (Le(x)) structure (Galβ1-4(Fucα1-3)GlcNAc-R) is a carbohydrate epitope comprising the stage-specific embryonic antigen-1 (SSEA-1) and CD15, and it is synthesized by α1,3-fucosyltransferase 9 (Fut9). 26244810 1 57 theme Fucα1-3 171:177 arg1 GlcNAc-R 179:186 Galβ1-4(Fucα1-3)GlcNAc-R 163:186 Galβ1-4(Fucα1-3)GlcNAc-R 163:186 The Lewis x (Le(x)) structure (Galβ1-4(Fucα1-3)GlcNAc-R) is a carbohydrate epitope comprising the stage-specific embryonic antigen-1 (SSEA-1) and CD15, and it is synthesized by α1,3-fucosyltransferase 9 (Fut9). 26244810 8 58 theme 24/32 1398:1402 arg1 glycoproteins 1404:1416 24/32 glycoproteins 1398:1416 24/32 glycoproteins 1398:1416 Our analyses demonstrated that 24/32 glycoproteins contained the Le(x) N-glycan structure in wild-type kidney; of these, Le(x) was lost from 21 in the knockout mice. 26244810 6 59 theme mice 1094:1097 arg1 homogenates 1051:1061 kidney homogenates 1044:1061 kidney homogenates of wild-type and Fut9 knockout mice 1044:1097 Glycopeptides carrying fucosylated glycans were collected by Aleuria aurantia lectin (AAL) affinity chromatography from kidney homogenates of wild-type and Fut9 knockout mice. 26244810 1 60 theme Lewis 136:140 arg1 x 142:142 Lewis x 136:142 The Lewis x (Le(x)) structure (Galβ1-4(Fucα1-3)GlcNAc-R) 132:187 The Lewis x (Le(x)) structure (Galβ1-4(Fucα1-3)GlcNAc-R) is a carbohydrate epitope comprising the stage-specific embryonic antigen-1 (SSEA-1) and CD15, and it is synthesized by α1,3-fucosyltransferase 9 (Fut9). 26244810 9 61 theme glycoproteins 1606:1618 arg1 identification 1573:1586 large-scale identification 1561:1586 large-scale identification of Le(x)-carrying glycoproteins from a native sample based on the site-specific glycome analysis 1561:1683 This is the first report of large-scale identification of Le(x)-carrying glycoproteins from a native sample based on the site-specific glycome analysis. 26244810 2 62 from function 446:453 arg1 tissues 464:470 these tissues 458:470 these tissues 458:470 Fut9 is expressed specifically in the stomach, kidney, brain, and in leukocytes, suggesting a specific function in these tissues. 26244810 6 63 theme Fut9 1080:1083 arg1 mice 1094:1097 wild-type and Fut9 knockout mice 1066:1097 wild-type and Fut9 knockout mice 1066:1097 Glycopeptides carrying fucosylated glycans were collected by Aleuria aurantia lectin (AAL) affinity chromatography from kidney homogenates of wild-type and Fut9 knockout mice. 26244810 0 64 theme Site-Specific 74:86 arg1 N-Glycan 88:95 Site-Specific N-Glycan 74:95 Site-Specific N-Glycan 74:95 Large-Scale Identification of N-Glycan Glycoproteins Carrying Lewis x and Site-Specific N-Glycan Alterations in Fut9 Knockout Mice. 26244810 3 65 theme spectrometry 513:524 arg1 profile 526:532 the N-linked glycan mass spectrometry profile 488:532 the N-linked glycan mass spectrometry profile of wild-type mouse kidney glycoproteins 488:572 In this study, the N-linked glycan mass spectrometry profile of wild-type mouse kidney glycoproteins revealed the presence of abundant terminal fucoses, which were lost following knockout of the Fut9 gene; the terminal fucose was therefore concluded to be Le(x). 26244810 1 66 theme Galβ1-4 163:169 arg1 structure 152:160 The Lewis x (Le(x)) structure 132:160 The Lewis x (Le(x)) structure (Galβ1-4(Fucα1-3)GlcNAc-R) 132:187 The Lewis x (Le(x)) structure (Galβ1-4(Fucα1-3)GlcNAc-R) is a carbohydrate epitope comprising the stage-specific embryonic antigen-1 (SSEA-1) and CD15, and it is synthesized by α1,3-fucosyltransferase 9 (Fut9). 26244810 1 66 theme Galβ1-4 163:169 arg1 GlcNAc-R 179:186 Galβ1-4(Fucα1-3)GlcNAc-R 163:186 Galβ1-4(Fucα1-3)GlcNAc-R 163:186 The Lewis x (Le(x)) structure (Galβ1-4(Fucα1-3)GlcNAc-R) is a carbohydrate epitope comprising the stage-specific embryonic antigen-1 (SSEA-1) and CD15, and it is synthesized by α1,3-fucosyltransferase 9 (Fut9). 26244810 6 67 theme wild-type 1066:1074 arg1 mice 1094:1097 wild-type and Fut9 knockout mice 1066:1097 wild-type and Fut9 knockout mice 1066:1097 Glycopeptides carrying fucosylated glycans were collected by Aleuria aurantia lectin (AAL) affinity chromatography from kidney homogenates of wild-type and Fut9 knockout mice. 26244810 7 68 from glycopeptides 1352:1364 arg1 assignment 1258:1267 dissociation-independent assignment 1233:1267 dissociation-independent assignment of glycopeptide signals 1233:1291 The site-specific N-glycomes on the glycopeptides were subsequently analyzed by adopting a new glycoproteomic technology composed of dissociation-independent assignment of glycopeptide signals and accurate mass-based prediction of the N-glycome on the glycopeptides. 26244810 7 68 from glycopeptides 1352:1364 arg1 prediction 1317:1326 accurate mass-based prediction 1297:1326 accurate mass-based prediction of the N-glycome on the glycopeptides 1297:1364 The site-specific N-glycomes on the glycopeptides were subsequently analyzed by adopting a new glycoproteomic technology composed of dissociation-independent assignment of glycopeptide signals and accurate mass-based prediction of the N-glycome on the glycopeptides. 26244810 8 69 theme N-glycan 1438:1445 arg1 structure 1447:1455 the Le(x) N-glycan structure 1428:1455 the Le(x) N-glycan structure in wild-type kidney 1428:1475 Our analyses demonstrated that 24/32 glycoproteins contained the Le(x) N-glycan structure in wild-type kidney; of these, Le(x) was lost from 21 in the knockout mice. 26244810 0 70 theme Fut9 112:115 arg1 Mice 126:129 Fut9 Knockout Mice 112:129 Fut9 Knockout Mice 112:129 Large-Scale Identification of N-Glycan Glycoproteins Carrying Lewis x and Site-Specific N-Glycan Alterations in Fut9 Knockout Mice. 26244810 9 71 from identification 1573:1586 arg1 sample 1634:1639 a native sample 1625:1639 a native sample based on the site-specific glycome analysis 1625:1683 This is the first report of large-scale identification of Le(x)-carrying glycoproteins from a native sample based on the site-specific glycome analysis. 26244810 2 72 theme specific 437:444 arg1 function 446:453 a specific function 435:453 a specific function in these tissues 435:470 Fut9 is expressed specifically in the stomach, kidney, brain, and in leukocytes, suggesting a specific function in these tissues. 26244810 1 73 dep x 142:142 arg1 Le 145:146 Le 145:146 Le(x) 145:149 The Lewis x (Le(x)) structure (Galβ1-4(Fucα1-3)GlcNAc-R) is a carbohydrate epitope comprising the stage-specific embryonic antigen-1 (SSEA-1) and CD15, and it is synthesized by α1,3-fucosyltransferase 9 (Fut9). 26244810 1 73 dep x 142:142 arg1 x 148:148 x 148:148 x 148:148 The Lewis x (Le(x)) structure (Galβ1-4(Fucα1-3)GlcNAc-R) is a carbohydrate epitope comprising the stage-specific embryonic antigen-1 (SSEA-1) and CD15, and it is synthesized by α1,3-fucosyltransferase 9 (Fut9). 26244810 6 74 theme fucosylated 947:957 arg1 glycans 959:965 fucosylated glycans 947:965 fucosylated glycans 947:965 Glycopeptides carrying fucosylated glycans were collected by Aleuria aurantia lectin (AAL) affinity chromatography from kidney homogenates of wild-type and Fut9 knockout mice. 26244810 4 75 theme specific 823:830 arg1 proteins 832:839 specific proteins 823:839 specific proteins 823:839 These results suggested that Le(x) presence is widespread rather than being limited to specific proteins. 26244810 0 76 theme N-Glycan 30:37 arg1 Glycoproteins 39:51 N-Glycan Glycoproteins 30:51 N-Glycan Glycoproteins 30:51 Large-Scale Identification of N-Glycan Glycoproteins Carrying Lewis x and Site-Specific N-Glycan Alterations in Fut9 Knockout Mice. 26244810 1 77 theme embryonic 245:253 arg1 antigen-1 255:263 the stage-specific embryonic antigen-1 226:263 the stage-specific embryonic antigen-1 (SSEA-1) 226:272 The Lewis x (Le(x)) structure (Galβ1-4(Fucα1-3)GlcNAc-R) is a carbohydrate epitope comprising the stage-specific embryonic antigen-1 (SSEA-1) and CD15, and it is synthesized by α1,3-fucosyltransferase 9 (Fut9). 26244810 1 77 theme embryonic 245:253 arg1 SSEA-1 266:271 SSEA-1 266:271 SSEA-1 266:271 The Lewis x (Le(x)) structure (Galβ1-4(Fucα1-3)GlcNAc-R) is a carbohydrate epitope comprising the stage-specific embryonic antigen-1 (SSEA-1) and CD15, and it is synthesized by α1,3-fucosyltransferase 9 (Fut9). 26244810 7 78 gly glycopeptides 1136:1148 arg2 glycopeptides 1136:1148 the glycopeptides 1132:1148 the glycopeptides 1132:1148 The site-specific N-glycomes on the glycopeptides were subsequently analyzed by adopting a new glycoproteomic technology composed of dissociation-independent assignment of glycopeptide signals and accurate mass-based prediction of the N-glycome on the glycopeptides. 26244810 7 79 theme new 1191:1193 arg1 technology 1210:1219 a new glycoproteomic technology 1189:1219 a new glycoproteomic technology composed of dissociation-independent assignment of glycopeptide signals and accurate mass-based prediction of the N-glycome on the glycopeptides 1189:1364 The site-specific N-glycomes on the glycopeptides were subsequently analyzed by adopting a new glycoproteomic technology composed of dissociation-independent assignment of glycopeptide signals and accurate mass-based prediction of the N-glycome on the glycopeptides. 26244810 3 80 theme glycoproteins 560:572 arg1 profile 526:532 the N-linked glycan mass spectrometry profile 488:532 the N-linked glycan mass spectrometry profile of wild-type mouse kidney glycoproteins 488:572 In this study, the N-linked glycan mass spectrometry profile of wild-type mouse kidney glycoproteins revealed the presence of abundant terminal fucoses, which were lost following knockout of the Fut9 gene; the terminal fucose was therefore concluded to be Le(x). 26244810 7 81 from prediction 1317:1326 arg1 glycopeptides 1352:1364 the glycopeptides 1348:1364 the glycopeptides 1348:1364 The site-specific N-glycomes on the glycopeptides were subsequently analyzed by adopting a new glycoproteomic technology composed of dissociation-independent assignment of glycopeptide signals and accurate mass-based prediction of the N-glycome on the glycopeptides. 26244810 3 82 link N-linked 492:499 arg1 profile 526:532 the N-linked glycan mass spectrometry profile 488:532 the N-linked glycan mass spectrometry profile of wild-type mouse kidney glycoproteins 488:572 In this study, the N-linked glycan mass spectrometry profile of wild-type mouse kidney glycoproteins revealed the presence of abundant terminal fucoses, which were lost following knockout of the Fut9 gene; the terminal fucose was therefore concluded to be Le(x). 26244810 3 83 theme mouse 547:551 arg1 glycoproteins 560:572 wild-type mouse kidney glycoproteins 537:572 wild-type mouse kidney glycoproteins 537:572 In this study, the N-linked glycan mass spectrometry profile of wild-type mouse kidney glycoproteins revealed the presence of abundant terminal fucoses, which were lost following knockout of the Fut9 gene; the terminal fucose was therefore concluded to be Le(x). 26244810 9 84 theme site-specific 1654:1666 arg1 analysis 1676:1683 the site-specific glycome analysis 1650:1683 the site-specific glycome analysis 1650:1683 This is the first report of large-scale identification of Le(x)-carrying glycoproteins from a native sample based on the site-specific glycome analysis. 26244810 0 85 theme x 68:68 arg1 Alterations 97:107 Lewis x and Site-Specific N-Glycan Alterations 62:107 Lewis x and Site-Specific N-Glycan Alterations in Fut9 Knockout Mice 62:129 Large-Scale Identification of N-Glycan Glycoproteins Carrying Lewis x and Site-Specific N-Glycan Alterations in Fut9 Knockout Mice. 26244810 6 86 gly fucosylated 947:957 arg1 glycans 959:965 fucosylated glycans 947:965 fucosylated glycans 947:965 Glycopeptides carrying fucosylated glycans were collected by Aleuria aurantia lectin (AAL) affinity chromatography from kidney homogenates of wild-type and Fut9 knockout mice. 26244810 9 87 from sample 1634:1639 arg1 identification 1573:1586 large-scale identification 1561:1586 large-scale identification of Le(x)-carrying glycoproteins from a native sample based on the site-specific glycome analysis 1561:1683 This is the first report of large-scale identification of Le(x)-carrying glycoproteins from a native sample based on the site-specific glycome analysis. 26244810 9 87 from sample 1634:1639 arg1 glycoproteins 1606:1618 Le(x)-carrying glycoproteins 1591:1618 Le(x)-carrying glycoproteins from a native sample based on the site-specific glycome analysis 1591:1683 This is the first report of large-scale identification of Le(x)-carrying glycoproteins from a native sample based on the site-specific glycome analysis. 26244810 6 88 theme aurantia 993:1000 arg1 AAL 1010:1012 AAL 1010:1012 AAL 1010:1012 Glycopeptides carrying fucosylated glycans were collected by Aleuria aurantia lectin (AAL) affinity chromatography from kidney homogenates of wild-type and Fut9 knockout mice. 26244810 6 88 theme aurantia 993:1000 arg1 lectin 1002:1007 Aleuria aurantia lectin 985:1007 Aleuria aurantia lectin (AAL) affinity chromatography 985:1037 Glycopeptides carrying fucosylated glycans were collected by Aleuria aurantia lectin (AAL) affinity chromatography from kidney homogenates of wild-type and Fut9 knockout mice. 26244810 8 89 contain contained 1418:1426 arg2 structure 1447:1455 the Le(x) N-glycan structure 1428:1455 the Le(x) N-glycan structure in wild-type kidney 1428:1475 Our analyses demonstrated that 24/32 glycoproteins contained the Le(x) N-glycan structure in wild-type kidney; of these, Le(x) was lost from 21 in the knockout mice. 26244810 8 89 contain contained 1418:1426 arg1 glycoproteins 1404:1416 24/32 glycoproteins 1398:1416 24/32 glycoproteins 1398:1416 Our analyses demonstrated that 24/32 glycoproteins contained the Le(x) N-glycan structure in wild-type kidney; of these, Le(x) was lost from 21 in the knockout mice. 26153065 6 0 theme U-69593 988:994 arg1 application 943:953 Acute application 937:953 Acute application of the opioid receptor agonists- U-69593, DAMGO and nociceptin- 937:1017 Acute application of the opioid receptor agonists- U-69593, DAMGO and nociceptin- inhibited adenylate cyclase (AC) activity in cells expressing KOP, MOP and NOP receptors respectively. 26153065 9 1 theme chronic 1655:1661 arg1 exposure 1677:1684 chronic buprenorphine exposure 1655:1684 chronic buprenorphine exposure 1655:1684 Our study demonstrated that MOP receptor could enhance AC regulation in the presence of coexpressed KOP and NOP receptors, and NOP receptor is essential for concentration-dependent AC superactivation elicited by chronic buprenorphine exposure. 26153065 6 2 theme receptor 969:976 arg1 U-69593 988:994 the opioid receptor agonists- U-69593 958:994 the opioid receptor agonists- U-69593 958:994 Acute application of the opioid receptor agonists- U-69593, DAMGO and nociceptin- inhibited adenylate cyclase (AC) activity in cells expressing KOP, MOP and NOP receptors respectively. 26153065 8 3 theme AC 1298:1299 arg1 superactivation 1301:1315 concentration-dependent AC superactivation 1274:1315 concentration-dependent AC superactivation 1274:1315 Chronic exposure to buprenorphine induced concentration-dependent AC superactivation in cells expressing KOP+NOP receptors, and the level of this superactivation was even higher in KOP+MOP+NOP-expressing cells. 26153065 0 4 from alteration 23:32 arg1 cells 94:98 human embryonic kidney 293 cells 67:98 human embryonic kidney 293 cells coexpressing κ-, μ-opioid and nociceptin receptors 67:149 Buprenorphine-elicited alteration of adenylate cyclase activity in human embryonic kidney 293 cells coexpressing κ-, μ-opioid and nociceptin receptors. 26153065 9 5 theme buprenorphine 1663:1675 arg1 exposure 1677:1684 chronic buprenorphine exposure 1655:1684 chronic buprenorphine exposure 1655:1684 Our study demonstrated that MOP receptor could enhance AC regulation in the presence of coexpressed KOP and NOP receptors, and NOP receptor is essential for concentration-dependent AC superactivation elicited by chronic buprenorphine exposure. 26153065 1 6 theme maintenance 169:179 arg1 drug 181:184 a maintenance drug 167:184 a maintenance drug for heroin addicts 167:203 Buprenorphine, a maintenance drug for heroin addicts, exerts its pharmacological function via κ- (KOP), μ-opioid (MOP) and nociceptin/opioid receptor-like 1 (NOP) receptors. 26153065 1 6 theme maintenance 169:179 arg1 Buprenorphine 152:164 Buprenorphine 152:164 Buprenorphine 152:164 Buprenorphine, a maintenance drug for heroin addicts, exerts its pharmacological function via κ- (KOP), μ-opioid (MOP) and nociceptin/opioid receptor-like 1 (NOP) receptors. 26153065 6 7 theme opioid 962:967 arg1 U-69593 988:994 the opioid receptor agonists- U-69593 958:994 the opioid receptor agonists- U-69593 958:994 Acute application of the opioid receptor agonists- U-69593, DAMGO and nociceptin- inhibited adenylate cyclase (AC) activity in cells expressing KOP, MOP and NOP receptors respectively. 26153065 8 8 theme KOP+NOP 1337:1343 arg1 receptors 1345:1353 KOP+NOP receptors 1337:1353 KOP+NOP receptors 1337:1353 Chronic exposure to buprenorphine induced concentration-dependent AC superactivation in cells expressing KOP+NOP receptors, and the level of this superactivation was even higher in KOP+MOP+NOP-expressing cells. 26153065 5 9 theme cytoplasmic 911:921 arg1 compartments 923:934 cytoplasmic compartments 911:934 cytoplasmic compartments 911:934 Immunoblotting and immunocytochemistry indicated that the expressed KOP, MOP and NOP receptors are N-linked glycoproteins and colocalized in cytoplasmic compartments. 26153065 7 10 theme AC 1169:1170 arg1 activity 1172:1179 AC activity 1169:1179 AC activity 1169:1179 Buprenorphine, when applied acutely, inhibited AC activity to ~90% in cells expressing KOP+MOP+NOP receptors. 26153065 2 11 dep or 439:440 arg1 NOP 463:465 NOP 463:465 NOP 463:465 Previously, we investigated its effects in an in vitro model expressing human MOP and NOP receptors individually or simultaneously (MOP, NOP, and MOP+NOP) in human embryonic kidney 293 cells. 26153065 2 11 dep or 439:440 arg1 MOP+NOP 472:478 MOP+NOP 472:478 MOP+NOP 472:478 Previously, we investigated its effects in an in vitro model expressing human MOP and NOP receptors individually or simultaneously (MOP, NOP, and MOP+NOP) in human embryonic kidney 293 cells. 26153065 2 11 dep or 439:440 arg1 MOP 458:460 MOP 458:460 MOP 458:460 Previously, we investigated its effects in an in vitro model expressing human MOP and NOP receptors individually or simultaneously (MOP, NOP, and MOP+NOP) in human embryonic kidney 293 cells. 26153065 4 12 theme Radioligand 671:681 arg1 binding 683:689 Radioligand binding 671:689 Radioligand binding with tritium-labelled diprenorphine 671:725 Radioligand binding with tritium-labelled diprenorphine confirmed the expression of KOP receptors. 26153065 1 13 theme μ-opioid 256:263 arg1 receptors 315:323 κ- (KOP), μ-opioid (MOP) and nociceptin/opioid receptor-like 1 (NOP) receptors 246:323 κ- (KOP), μ-opioid (MOP) and nociceptin/opioid receptor-like 1 (NOP) receptors 246:323 Buprenorphine, a maintenance drug for heroin addicts, exerts its pharmacological function via κ- (KOP), μ-opioid (MOP) and nociceptin/opioid receptor-like 1 (NOP) receptors. 26153065 4 14 theme tritium-labelled 696:711 arg1 diprenorphine 713:725 tritium-labelled diprenorphine 696:725 tritium-labelled diprenorphine 696:725 Radioligand binding with tritium-labelled diprenorphine confirmed the expression of KOP receptors. 26153065 5 15 theme expressed 828:836 arg1 receptors 855:863 the expressed KOP, MOP and NOP receptors 824:863 the expressed KOP, MOP and NOP receptors 824:863 Immunoblotting and immunocytochemistry indicated that the expressed KOP, MOP and NOP receptors are N-linked glycoproteins and colocalized in cytoplasmic compartments. 26153065 5 15 theme expressed 828:836 arg1 glycoproteins 878:890 N-linked glycoproteins 869:890 N-linked glycoproteins 869:890 Immunoblotting and immunocytochemistry indicated that the expressed KOP, MOP and NOP receptors are N-linked glycoproteins and colocalized in cytoplasmic compartments. 26153065 9 16 theme receptors 1555:1563 arg1 presence 1519:1526 the presence 1515:1526 the presence of coexpressed KOP and NOP receptors 1515:1563 Our study demonstrated that MOP receptor could enhance AC regulation in the presence of coexpressed KOP and NOP receptors, and NOP receptor is essential for concentration-dependent AC superactivation elicited by chronic buprenorphine exposure. 26153065 8 17 theme Chronic 1232:1238 arg1 exposure 1240:1247 Chronic exposure 1232:1247 Chronic exposure to buprenorphine 1232:1264 Chronic exposure to buprenorphine induced concentration-dependent AC superactivation in cells expressing KOP+NOP receptors, and the level of this superactivation was even higher in KOP+MOP+NOP-expressing cells. 26153065 2 18 theme NOP 412:414 arg1 receptors 416:424 human MOP and NOP receptors 398:424 receptors 416:424 Previously, we investigated its effects in an in vitro model expressing human MOP and NOP receptors individually or simultaneously (MOP, NOP, and MOP+NOP) in human embryonic kidney 293 cells. 26153065 7 19 theme ~90 1184:1186 arg1 % 1187:1187 ~90% 1184:1187 ~90% 1184:1187 Buprenorphine, when applied acutely, inhibited AC activity to ~90% in cells expressing KOP+MOP+NOP receptors. 26153065 1 20 theme heroin 190:195 arg1 addicts 197:203 heroin addicts 190:203 heroin addicts 190:203 Buprenorphine, a maintenance drug for heroin addicts, exerts its pharmacological function via κ- (KOP), μ-opioid (MOP) and nociceptin/opioid receptor-like 1 (NOP) receptors. 26153065 0 21 theme Buprenorphine-elicited 0:21 arg1 alteration 23:32 Buprenorphine-elicited alteration 0:32 Buprenorphine-elicited alteration of adenylate cyclase activity in human embryonic kidney 293 cells coexpressing κ-, μ-opioid and nociceptin receptors. 0:150 Buprenorphine-elicited alteration of adenylate cyclase activity in human embryonic kidney 293 cells coexpressing κ-, μ-opioid and nociceptin receptors. 26153065 3 22 dep or 612:613 arg1 KOP+MOP 636:642 KOP+MOP 636:642 KOP+MOP 636:642 Here, we expanded this cell model by expressing human KOP, MOP and NOP receptors individually or simultaneously (KOP, KOP+MOP, KOP+NOP and KOP+MOP+NOP). 26153065 3 22 dep or 612:613 arg1 KOP 631:633 KOP 631:633 KOP 631:633 Here, we expanded this cell model by expressing human KOP, MOP and NOP receptors individually or simultaneously (KOP, KOP+MOP, KOP+NOP and KOP+MOP+NOP). 26153065 3 22 dep or 612:613 arg1 KOP+MOP+NOP 657:667 KOP+MOP+NOP 657:667 KOP+MOP+NOP 657:667 Here, we expanded this cell model by expressing human KOP, MOP and NOP receptors individually or simultaneously (KOP, KOP+MOP, KOP+NOP and KOP+MOP+NOP). 26153065 3 22 dep or 612:613 arg1 KOP+NOP 645:651 KOP+NOP 645:651 KOP+NOP 645:651 Here, we expanded this cell model by expressing human KOP, MOP and NOP receptors individually or simultaneously (KOP, KOP+MOP, KOP+NOP and KOP+MOP+NOP). 26153065 3 23 theme NOP 585:587 arg1 receptors 589:597 human KOP, MOP and NOP receptors 566:597 human KOP, MOP and NOP receptors 566:597 Here, we expanded this cell model by expressing human KOP, MOP and NOP receptors individually or simultaneously (KOP, KOP+MOP, KOP+NOP and KOP+MOP+NOP). 26153065 5 24 theme KOP 838:840 arg1 receptors 855:863 the expressed KOP, MOP and NOP receptors 824:863 the expressed KOP, MOP and NOP receptors 824:863 Immunoblotting and immunocytochemistry indicated that the expressed KOP, MOP and NOP receptors are N-linked glycoproteins and colocalized in cytoplasmic compartments. 26153065 5 24 theme KOP 838:840 arg1 glycoproteins 878:890 N-linked glycoproteins 869:890 N-linked glycoproteins 869:890 Immunoblotting and immunocytochemistry indicated that the expressed KOP, MOP and NOP receptors are N-linked glycoproteins and colocalized in cytoplasmic compartments. 26153065 0 25 theme adenylate 37:45 arg1 cyclase 47:53 adenylate cyclase 37:53 adenylate cyclase activity 37:62 Buprenorphine-elicited alteration of adenylate cyclase activity in human embryonic kidney 293 cells coexpressing κ-, μ-opioid and nociceptin receptors. 26153065 6 26 theme Acute 937:941 arg1 application 943:953 Acute application 937:953 Acute application of the opioid receptor agonists- U-69593, DAMGO and nociceptin- 937:1017 Acute application of the opioid receptor agonists- U-69593, DAMGO and nociceptin- inhibited adenylate cyclase (AC) activity in cells expressing KOP, MOP and NOP receptors respectively. 26153065 2 27 theme kidney 500:505 arg1 cells 511:515 human embryonic kidney 293 cells 484:515 human embryonic kidney 293 cells 484:515 Previously, we investigated its effects in an in vitro model expressing human MOP and NOP receptors individually or simultaneously (MOP, NOP, and MOP+NOP) in human embryonic kidney 293 cells. 26153065 6 28 theme NOP 1094:1096 arg1 receptors 1098:1106 KOP, MOP and NOP receptors 1081:1106 KOP, MOP and NOP receptors 1081:1106 Acute application of the opioid receptor agonists- U-69593, DAMGO and nociceptin- inhibited adenylate cyclase (AC) activity in cells expressing KOP, MOP and NOP receptors respectively. 26153065 9 29 theme NOP 1570:1572 arg1 receptor 1574:1581 NOP receptor 1570:1581 NOP receptor 1570:1581 Our study demonstrated that MOP receptor could enhance AC regulation in the presence of coexpressed KOP and NOP receptors, and NOP receptor is essential for concentration-dependent AC superactivation elicited by chronic buprenorphine exposure. 26153065 8 30 theme superactivation 1378:1392 arg1 level 1364:1368 the level 1360:1368 the level of this superactivation 1360:1392 Chronic exposure to buprenorphine induced concentration-dependent AC superactivation in cells expressing KOP+NOP receptors, and the level of this superactivation was even higher in KOP+MOP+NOP-expressing cells. 26153065 8 30 theme superactivation 1378:1392 arg1 higher 1403:1408 higher 1403:1408 higher 1403:1408 Chronic exposure to buprenorphine induced concentration-dependent AC superactivation in cells expressing KOP+NOP receptors, and the level of this superactivation was even higher in KOP+MOP+NOP-expressing cells. 26153065 6 31 theme adenylate 1029:1037 arg1 AC 1048:1049 AC 1048:1049 AC 1048:1049 Acute application of the opioid receptor agonists- U-69593, DAMGO and nociceptin- inhibited adenylate cyclase (AC) activity in cells expressing KOP, MOP and NOP receptors respectively. 26153065 6 31 theme adenylate 1029:1037 arg1 cyclase 1039:1045 adenylate cyclase 1029:1045 adenylate cyclase (AC) activity in cells expressing KOP, MOP and NOP receptors 1029:1106 Acute application of the opioid receptor agonists- U-69593, DAMGO and nociceptin- inhibited adenylate cyclase (AC) activity in cells expressing KOP, MOP and NOP receptors respectively. 26153065 2 32 theme human 398:402 arg1 MOP 404:406 human MOP and NOP receptors 398:424 MOP 404:406 Previously, we investigated its effects in an in vitro model expressing human MOP and NOP receptors individually or simultaneously (MOP, NOP, and MOP+NOP) in human embryonic kidney 293 cells. 26153065 4 33 with binding 683:689 arg1 diprenorphine 713:725 tritium-labelled diprenorphine 696:725 tritium-labelled diprenorphine 696:725 Radioligand binding with tritium-labelled diprenorphine confirmed the expression of KOP receptors. 26153065 2 34 theme embryonic 490:498 arg1 kidney 500:505 human embryonic kidney 293 484:509 human embryonic kidney 293 cells 484:515 Previously, we investigated its effects in an in vitro model expressing human MOP and NOP receptors individually or simultaneously (MOP, NOP, and MOP+NOP) in human embryonic kidney 293 cells. 26153065 5 35 theme NOP 851:853 arg1 receptors 855:863 the expressed KOP, MOP and NOP receptors 824:863 the expressed KOP, MOP and NOP receptors 824:863 Immunoblotting and immunocytochemistry indicated that the expressed KOP, MOP and NOP receptors are N-linked glycoproteins and colocalized in cytoplasmic compartments. 26153065 5 35 theme NOP 851:853 arg1 glycoproteins 878:890 N-linked glycoproteins 869:890 N-linked glycoproteins 869:890 Immunoblotting and immunocytochemistry indicated that the expressed KOP, MOP and NOP receptors are N-linked glycoproteins and colocalized in cytoplasmic compartments. 26153065 9 36 theme coexpressed 1531:1541 arg1 receptors 1555:1563 coexpressed KOP and NOP receptors 1531:1563 coexpressed KOP and NOP receptors 1531:1563 Our study demonstrated that MOP receptor could enhance AC regulation in the presence of coexpressed KOP and NOP receptors, and NOP receptor is essential for concentration-dependent AC superactivation elicited by chronic buprenorphine exposure. 26153065 9 37 theme MOP 1471:1473 arg1 receptor 1475:1482 MOP receptor 1471:1482 MOP receptor 1471:1482 Our study demonstrated that MOP receptor could enhance AC regulation in the presence of coexpressed KOP and NOP receptors, and NOP receptor is essential for concentration-dependent AC superactivation elicited by chronic buprenorphine exposure. 26153065 0 38 theme activity 55:62 arg1 alteration 23:32 Buprenorphine-elicited alteration 0:32 Buprenorphine-elicited alteration of adenylate cyclase activity in human embryonic kidney 293 cells coexpressing κ-, μ-opioid and nociceptin receptors. 0:150 Buprenorphine-elicited alteration of adenylate cyclase activity in human embryonic kidney 293 cells coexpressing κ-, μ-opioid and nociceptin receptors. 26153065 9 39 theme AC 1498:1499 arg1 regulation 1501:1510 AC regulation 1498:1510 AC regulation 1498:1510 Our study demonstrated that MOP receptor could enhance AC regulation in the presence of coexpressed KOP and NOP receptors, and NOP receptor is essential for concentration-dependent AC superactivation elicited by chronic buprenorphine exposure. 26153065 2 40 theme human 484:488 arg1 kidney 500:505 human embryonic kidney 293 484:509 human embryonic kidney 293 cells 484:515 Previously, we investigated its effects in an in vitro model expressing human MOP and NOP receptors individually or simultaneously (MOP, NOP, and MOP+NOP) in human embryonic kidney 293 cells. 26153065 3 41 theme MOP 577:579 arg1 receptors 589:597 human KOP, MOP and NOP receptors 566:597 human KOP, MOP and NOP receptors 566:597 Here, we expanded this cell model by expressing human KOP, MOP and NOP receptors individually or simultaneously (KOP, KOP+MOP, KOP+NOP and KOP+MOP+NOP). 26153065 4 42 theme KOP 755:757 arg1 receptors 759:767 KOP receptors 755:767 KOP receptors 755:767 Radioligand binding with tritium-labelled diprenorphine confirmed the expression of KOP receptors. 26153065 6 43 theme cyclase 1039:1045 arg1 activity 1052:1059 adenylate cyclase (AC) activity 1029:1059 adenylate cyclase (AC) activity in cells expressing KOP, MOP and NOP receptors 1029:1106 Acute application of the opioid receptor agonists- U-69593, DAMGO and nociceptin- inhibited adenylate cyclase (AC) activity in cells expressing KOP, MOP and NOP receptors respectively. 26153065 6 44 theme nociceptin- 1007:1017 arg1 application 943:953 Acute application 937:953 Acute application of the opioid receptor agonists- U-69593, DAMGO and nociceptin- 937:1017 Acute application of the opioid receptor agonists- U-69593, DAMGO and nociceptin- inhibited adenylate cyclase (AC) activity in cells expressing KOP, MOP and NOP receptors respectively. 26153065 0 45 theme cyclase 47:53 arg1 activity 55:62 adenylate cyclase activity 37:62 adenylate cyclase activity 37:62 Buprenorphine-elicited alteration of adenylate cyclase activity in human embryonic kidney 293 cells coexpressing κ-, μ-opioid and nociceptin receptors. 26153065 1 46 theme nociceptin/opioid 275:291 arg1 receptors 315:323 κ- (KOP), μ-opioid (MOP) and nociceptin/opioid receptor-like 1 (NOP) receptors 246:323 κ- (KOP), μ-opioid (MOP) and nociceptin/opioid receptor-like 1 (NOP) receptors 246:323 Buprenorphine, a maintenance drug for heroin addicts, exerts its pharmacological function via κ- (KOP), μ-opioid (MOP) and nociceptin/opioid receptor-like 1 (NOP) receptors. 26153065 3 47 theme human 566:570 arg1 KOP 572:574 human KOP 566:574 human KOP 566:574 Here, we expanded this cell model by expressing human KOP, MOP and NOP receptors individually or simultaneously (KOP, KOP+MOP, KOP+NOP and KOP+MOP+NOP). 26153065 2 48 dep in 372:373 arg1 vitro 375:379 vitro 375:379 vitro 375:379 Previously, we investigated its effects in an in vitro model expressing human MOP and NOP receptors individually or simultaneously (MOP, NOP, and MOP+NOP) in human embryonic kidney 293 cells. 26153065 1 49 theme pharmacological 217:231 arg1 function 233:240 its pharmacological function 213:240 its pharmacological function 213:240 Buprenorphine, a maintenance drug for heroin addicts, exerts its pharmacological function via κ- (KOP), μ-opioid (MOP) and nociceptin/opioid receptor-like 1 (NOP) receptors. 26153065 0 50 theme human 67:71 arg1 kidney 83:88 human embryonic kidney 293 67:92 human embryonic kidney 293 cells coexpressing κ-, μ-opioid and nociceptin receptors 67:149 Buprenorphine-elicited alteration of adenylate cyclase activity in human embryonic kidney 293 cells coexpressing κ-, μ-opioid and nociceptin receptors. 26153065 1 51 theme receptor-like 293:305 arg1 receptors 315:323 κ- (KOP), μ-opioid (MOP) and nociceptin/opioid receptor-like 1 (NOP) receptors 246:323 κ- (KOP), μ-opioid (MOP) and nociceptin/opioid receptor-like 1 (NOP) receptors 246:323 Buprenorphine, a maintenance drug for heroin addicts, exerts its pharmacological function via κ- (KOP), μ-opioid (MOP) and nociceptin/opioid receptor-like 1 (NOP) receptors. 26153065 5 52 link N-linked 869:876 arg1 receptors 855:863 the expressed KOP, MOP and NOP receptors 824:863 the expressed KOP, MOP and NOP receptors 824:863 Immunoblotting and immunocytochemistry indicated that the expressed KOP, MOP and NOP receptors are N-linked glycoproteins and colocalized in cytoplasmic compartments. 26153065 5 52 link N-linked 869:876 arg1 glycoproteins 878:890 N-linked glycoproteins 869:890 N-linked glycoproteins 869:890 Immunoblotting and immunocytochemistry indicated that the expressed KOP, MOP and NOP receptors are N-linked glycoproteins and colocalized in cytoplasmic compartments. 26153065 3 53 theme KOP 572:574 arg1 receptors 589:597 human KOP, MOP and NOP receptors 566:597 human KOP, MOP and NOP receptors 566:597 Here, we expanded this cell model by expressing human KOP, MOP and NOP receptors individually or simultaneously (KOP, KOP+MOP, KOP+NOP and KOP+MOP+NOP). 26153065 0 54 theme nociceptin 130:139 arg1 receptors 141:149 nociceptin receptors 130:149 nociceptin receptors 130:149 Buprenorphine-elicited alteration of adenylate cyclase activity in human embryonic kidney 293 cells coexpressing κ-, μ-opioid and nociceptin receptors. 26153065 4 55 theme receptors 759:767 arg1 expression 741:750 the expression 737:750 the expression of KOP receptors 737:767 Radioligand binding with tritium-labelled diprenorphine confirmed the expression of KOP receptors. 26153065 6 56 theme MOP 1086:1088 arg1 receptors 1098:1106 KOP, MOP and NOP receptors 1081:1106 KOP, MOP and NOP receptors 1081:1106 Acute application of the opioid receptor agonists- U-69593, DAMGO and nociceptin- inhibited adenylate cyclase (AC) activity in cells expressing KOP, MOP and NOP receptors respectively. 26153065 7 57 theme KOP+MOP+NOP 1209:1219 arg1 receptors 1221:1229 KOP+MOP+NOP receptors 1209:1229 KOP+MOP+NOP receptors 1209:1229 Buprenorphine, when applied acutely, inhibited AC activity to ~90% in cells expressing KOP+MOP+NOP receptors. 26153065 9 58 theme AC 1624:1625 arg1 superactivation 1627:1641 concentration-dependent AC superactivation 1600:1641 concentration-dependent AC superactivation elicited by chronic buprenorphine exposure 1600:1684 Our study demonstrated that MOP receptor could enhance AC regulation in the presence of coexpressed KOP and NOP receptors, and NOP receptor is essential for concentration-dependent AC superactivation elicited by chronic buprenorphine exposure. 26153065 5 59 theme N-linked 869:876 arg1 receptors 855:863 the expressed KOP, MOP and NOP receptors 824:863 the expressed KOP, MOP and NOP receptors 824:863 Immunoblotting and immunocytochemistry indicated that the expressed KOP, MOP and NOP receptors are N-linked glycoproteins and colocalized in cytoplasmic compartments. 26153065 5 59 theme N-linked 869:876 arg1 glycoproteins 878:890 N-linked glycoproteins 869:890 N-linked glycoproteins 869:890 Immunoblotting and immunocytochemistry indicated that the expressed KOP, MOP and NOP receptors are N-linked glycoproteins and colocalized in cytoplasmic compartments. 26153065 6 60 theme KOP 1081:1083 arg1 receptors 1098:1106 KOP, MOP and NOP receptors 1081:1106 KOP, MOP and NOP receptors 1081:1106 Acute application of the opioid receptor agonists- U-69593, DAMGO and nociceptin- inhibited adenylate cyclase (AC) activity in cells expressing KOP, MOP and NOP receptors respectively. 26153065 6 61 theme DAMGO 997:1001 arg1 application 943:953 Acute application 937:953 Acute application of the opioid receptor agonists- U-69593, DAMGO and nociceptin- 937:1017 Acute application of the opioid receptor agonists- U-69593, DAMGO and nociceptin- inhibited adenylate cyclase (AC) activity in cells expressing KOP, MOP and NOP receptors respectively. 26153065 9 62 theme KOP 1543:1545 arg1 receptors 1555:1563 coexpressed KOP and NOP receptors 1531:1563 coexpressed KOP and NOP receptors 1531:1563 Our study demonstrated that MOP receptor could enhance AC regulation in the presence of coexpressed KOP and NOP receptors, and NOP receptor is essential for concentration-dependent AC superactivation elicited by chronic buprenorphine exposure. 26153065 5 63 theme MOP 843:845 arg1 receptors 855:863 the expressed KOP, MOP and NOP receptors 824:863 the expressed KOP, MOP and NOP receptors 824:863 Immunoblotting and immunocytochemistry indicated that the expressed KOP, MOP and NOP receptors are N-linked glycoproteins and colocalized in cytoplasmic compartments. 26153065 5 63 theme MOP 843:845 arg1 glycoproteins 878:890 N-linked glycoproteins 869:890 N-linked glycoproteins 869:890 Immunoblotting and immunocytochemistry indicated that the expressed KOP, MOP and NOP receptors are N-linked glycoproteins and colocalized in cytoplasmic compartments. 26153065 8 64 theme concentration-dependent 1274:1296 arg1 superactivation 1301:1315 concentration-dependent AC superactivation 1274:1315 concentration-dependent AC superactivation 1274:1315 Chronic exposure to buprenorphine induced concentration-dependent AC superactivation in cells expressing KOP+NOP receptors, and the level of this superactivation was even higher in KOP+MOP+NOP-expressing cells. 26153065 0 65 theme kidney 83:88 arg1 cells 94:98 human embryonic kidney 293 cells 67:98 human embryonic kidney 293 cells coexpressing κ-, μ-opioid and nociceptin receptors 67:149 Buprenorphine-elicited alteration of adenylate cyclase activity in human embryonic kidney 293 cells coexpressing κ-, μ-opioid and nociceptin receptors. 26153065 2 66 theme in 372:373 arg1 model 381:385 an in vitro model 369:385 an in vitro model expressing human MOP and NOP receptors 369:424 Previously, we investigated its effects in an in vitro model expressing human MOP and NOP receptors individually or simultaneously (MOP, NOP, and MOP+NOP) in human embryonic kidney 293 cells. 26153065 3 67 theme cell 541:544 arg1 model 546:550 this cell model 536:550 this cell model 536:550 Here, we expanded this cell model by expressing human KOP, MOP and NOP receptors individually or simultaneously (KOP, KOP+MOP, KOP+NOP and KOP+MOP+NOP). 26153065 6 68 from activity 1052:1059 arg1 cells 1064:1068 cells 1064:1068 cells expressing KOP, MOP and NOP receptors 1064:1106 Acute application of the opioid receptor agonists- U-69593, DAMGO and nociceptin- inhibited adenylate cyclase (AC) activity in cells expressing KOP, MOP and NOP receptors respectively. 26153065 1 69 theme κ- 246:247 arg1 receptors 315:323 κ- (KOP), μ-opioid (MOP) and nociceptin/opioid receptor-like 1 (NOP) receptors 246:323 κ- (KOP), μ-opioid (MOP) and nociceptin/opioid receptor-like 1 (NOP) receptors 246:323 Buprenorphine, a maintenance drug for heroin addicts, exerts its pharmacological function via κ- (KOP), μ-opioid (MOP) and nociceptin/opioid receptor-like 1 (NOP) receptors. 26153065 0 70 theme embryonic 73:81 arg1 kidney 83:88 human embryonic kidney 293 67:92 human embryonic kidney 293 cells coexpressing κ-, μ-opioid and nociceptin receptors 67:149 Buprenorphine-elicited alteration of adenylate cyclase activity in human embryonic kidney 293 cells coexpressing κ-, μ-opioid and nociceptin receptors. 26153065 1 71 theme NOP 310:312 arg1 receptors 315:323 κ- (KOP), μ-opioid (MOP) and nociceptin/opioid receptor-like 1 (NOP) receptors 246:323 κ- (KOP), μ-opioid (MOP) and nociceptin/opioid receptor-like 1 (NOP) receptors 246:323 Buprenorphine, a maintenance drug for heroin addicts, exerts its pharmacological function via κ- (KOP), μ-opioid (MOP) and nociceptin/opioid receptor-like 1 (NOP) receptors. 26153065 8 72 theme KOP+MOP+NOP-expressing 1413:1434 arg1 cells 1436:1440 KOP+MOP+NOP-expressing cells 1413:1440 KOP+MOP+NOP-expressing cells 1413:1440 Chronic exposure to buprenorphine induced concentration-dependent AC superactivation in cells expressing KOP+NOP receptors, and the level of this superactivation was even higher in KOP+MOP+NOP-expressing cells. 26153065 9 73 theme NOP 1551:1553 arg1 receptors 1555:1563 coexpressed KOP and NOP receptors 1531:1563 coexpressed KOP and NOP receptors 1531:1563 Our study demonstrated that MOP receptor could enhance AC regulation in the presence of coexpressed KOP and NOP receptors, and NOP receptor is essential for concentration-dependent AC superactivation elicited by chronic buprenorphine exposure. 26153065 5 74 gly glycoproteins 878:890 arg1 receptors 855:863 the expressed KOP, MOP and NOP receptors 824:863 the expressed KOP, MOP and NOP receptors 824:863 Immunoblotting and immunocytochemistry indicated that the expressed KOP, MOP and NOP receptors are N-linked glycoproteins and colocalized in cytoplasmic compartments. 26153065 5 74 gly glycoproteins 878:890 arg1 glycoproteins 878:890 N-linked glycoproteins 869:890 N-linked glycoproteins 869:890 Immunoblotting and immunocytochemistry indicated that the expressed KOP, MOP and NOP receptors are N-linked glycoproteins and colocalized in cytoplasmic compartments. 26153065 9 75 theme concentration-dependent 1600:1622 arg1 superactivation 1627:1641 concentration-dependent AC superactivation 1600:1641 concentration-dependent AC superactivation elicited by chronic buprenorphine exposure 1600:1684 Our study demonstrated that MOP receptor could enhance AC regulation in the presence of coexpressed KOP and NOP receptors, and NOP receptor is essential for concentration-dependent AC superactivation elicited by chronic buprenorphine exposure. 26153065 6 76 theme agonists- 978:986 arg1 U-69593 988:994 the opioid receptor agonists- U-69593 958:994 the opioid receptor agonists- U-69593 958:994 Acute application of the opioid receptor agonists- U-69593, DAMGO and nociceptin- inhibited adenylate cyclase (AC) activity in cells expressing KOP, MOP and NOP receptors respectively. 25422949 2 0 theme basic 258:262 arg1 factor 282:287 a maltose-binding protein (MBP)-linked basic fibroblast growth factor 219:287 a maltose-binding protein (MBP)-linked basic fibroblast growth factor (FGF2)-immobilised polystyrene surface (PS-MBP-FGF2) 219:340 In this study, a maltose-binding protein (MBP)-linked basic fibroblast growth factor (FGF2)-immobilised polystyrene surface (PS-MBP-FGF2) was applied as an artificial matrix to regulate integrin-mediated signalling. 25422949 2 0 theme basic 258:262 arg1 FGF2 290:293 FGF2 290:293 FGF2 290:293 In this study, a maltose-binding protein (MBP)-linked basic fibroblast growth factor (FGF2)-immobilised polystyrene surface (PS-MBP-FGF2) was applied as an artificial matrix to regulate integrin-mediated signalling. 25422949 3 1 theme different 510:518 arg1 mechanisms 520:529 two different mechanisms 506:529 two different mechanisms of cell adhesion; (i) FGF2-heparan sulphate proteoglycan (HSPG)-mediated adhesion vs. (ii) fibronectin (FN)-integrin-mediated adhesion 506:664 We sought to characterise human mesenchymal-stem cell (hMSC) behaviour in response to two different mechanisms of cell adhesion; (i) FGF2-heparan sulphate proteoglycan (HSPG)-mediated adhesion vs. (ii) fibronectin (FN)-integrin-mediated adhesion. 25422949 5 2 theme cell 824:827 arg1 proliferation 829:841 cell proliferation 824:841 cell proliferation 824:841 The phosphorylation of focal adhesion kinase, cytoskeletal re-organisation, and cell proliferation were restricted in hMSCs adhering to PS-MBP-FGF2 compared to FN-coated surface. 25422949 8 3 link N-linked 1278:1285 arg1 structures 1294:1303 the N-linked glycan structures 1274:1303 the N-linked glycan structures of hMSCs depending on the cell adhesion mechanism using mass spectrometry (MS)-based quantitative techniques 1274:1412 Furthermore, we characterised the N-linked glycan structures of hMSCs depending on the cell adhesion mechanism using mass spectrometry (MS)-based quantitative techniques. 25422949 2 4 link -linked 250:256 arg1 factor 282:287 a maltose-binding protein (MBP)-linked basic fibroblast growth factor 219:287 a maltose-binding protein (MBP)-linked basic fibroblast growth factor (FGF2)-immobilised polystyrene surface (PS-MBP-FGF2) 219:340 In this study, a maltose-binding protein (MBP)-linked basic fibroblast growth factor (FGF2)-immobilised polystyrene surface (PS-MBP-FGF2) was applied as an artificial matrix to regulate integrin-mediated signalling. 25422949 2 4 link -linked 250:256 arg1 FGF2 290:293 FGF2 290:293 FGF2 290:293 In this study, a maltose-binding protein (MBP)-linked basic fibroblast growth factor (FGF2)-immobilised polystyrene surface (PS-MBP-FGF2) was applied as an artificial matrix to regulate integrin-mediated signalling. 25422949 1 5 theme stem 184:187 arg1 function 194:201 stem cell function 184:201 stem cell function 184:201 Control of cell-matrix adhesion has become an important issue in the regulation of stem cell function. 25422949 6 6 theme markers 941:947 arg1 Expression 923:932 Expression 923:932 Expression of MSC markers, such as CD105, CD90 and CD166, 923:979 Expression of MSC markers, such as CD105, CD90 and CD166, decreased in hMSCs expanded on PS-MBP-FGF2 compared to expression in cells expanded on FN-coated surface. 25422949 8 7 theme cell 1331:1334 arg1 mechanism 1345:1353 the cell adhesion mechanism 1327:1353 the cell adhesion mechanism using mass spectrometry (MS)-based quantitative techniques 1327:1412 Furthermore, we characterised the N-linked glycan structures of hMSCs depending on the cell adhesion mechanism using mass spectrometry (MS)-based quantitative techniques. 25422949 3 8 theme adhesion 539:546 arg1 mechanisms 520:529 two different mechanisms 506:529 two different mechanisms of cell adhesion; (i) FGF2-heparan sulphate proteoglycan (HSPG)-mediated adhesion vs. (ii) fibronectin (FN)-integrin-mediated adhesion 506:664 We sought to characterise human mesenchymal-stem cell (hMSC) behaviour in response to two different mechanisms of cell adhesion; (i) FGF2-heparan sulphate proteoglycan (HSPG)-mediated adhesion vs. (ii) fibronectin (FN)-integrin-mediated adhesion. 25422949 9 9 theme 2,3-sialylated 1441:1454 arg1 marker 1477:1482 a potential marker 1465:1482 a potential marker of stem cell function 1465:1504 MS analysis revealed that 2,3-sialylated glycans, a potential marker of stem cell function, were more abundant on hMSCs expanded on FN-coated surface than on those expanded on PS-MBP-FGF2. 25422949 9 9 theme 2,3-sialylated 1441:1454 arg1 glycans 1456:1462 2,3-sialylated glycans 1441:1462 2,3-sialylated glycans 1441:1462 MS analysis revealed that 2,3-sialylated glycans, a potential marker of stem cell function, were more abundant on hMSCs expanded on FN-coated surface than on those expanded on PS-MBP-FGF2. 25422949 1 10 theme adhesion 124:131 arg1 Control 101:107 Control 101:107 Control of cell-matrix adhesion 101:131 Control of cell-matrix adhesion has become an important issue in the regulation of stem cell function. 25422949 3 11 theme sulphate 566:573 arg1 HSPG 589:592 HSPG 589:592 HSPG 589:592 We sought to characterise human mesenchymal-stem cell (hMSC) behaviour in response to two different mechanisms of cell adhesion; (i) FGF2-heparan sulphate proteoglycan (HSPG)-mediated adhesion vs. (ii) fibronectin (FN)-integrin-mediated adhesion. 25422949 3 11 theme sulphate 566:573 arg1 proteoglycan 575:586 (i) FGF2-heparan sulphate proteoglycan 549:586 (i) FGF2-heparan sulphate proteoglycan (HSPG)-mediated adhesion 549:611 We sought to characterise human mesenchymal-stem cell (hMSC) behaviour in response to two different mechanisms of cell adhesion; (i) FGF2-heparan sulphate proteoglycan (HSPG)-mediated adhesion vs. (ii) fibronectin (FN)-integrin-mediated adhesion. 25422949 5 12 theme adhesion 773:780 arg1 kinase 782:787 focal adhesion kinase 767:787 focal adhesion kinase 767:787 The phosphorylation of focal adhesion kinase, cytoskeletal re-organisation, and cell proliferation were restricted in hMSCs adhering to PS-MBP-FGF2 compared to FN-coated surface. 25422949 10 13 theme biomaterials 1742:1753 arg1 design 1732:1737 the design 1728:1737 the design of biomaterials to control stem cell fate 1728:1779 Thus, the differentiation potential of hMSCs is controlled by the type of adhesion substrate that might provide an idea for the design of biomaterials to control stem cell fate. 25422949 9 14 theme potential 1467:1475 arg1 marker 1477:1482 a potential marker 1465:1482 a potential marker of stem cell function 1465:1504 MS analysis revealed that 2,3-sialylated glycans, a potential marker of stem cell function, were more abundant on hMSCs expanded on FN-coated surface than on those expanded on PS-MBP-FGF2. 25422949 9 14 theme potential 1467:1475 arg1 glycans 1456:1462 2,3-sialylated glycans 1441:1462 2,3-sialylated glycans 1441:1462 MS analysis revealed that 2,3-sialylated glycans, a potential marker of stem cell function, were more abundant on hMSCs expanded on FN-coated surface than on those expanded on PS-MBP-FGF2. 25422949 2 15 theme integrin-mediated 390:406 arg1 signalling 408:417 integrin-mediated signalling 390:417 integrin-mediated signalling 390:417 In this study, a maltose-binding protein (MBP)-linked basic fibroblast growth factor (FGF2)-immobilised polystyrene surface (PS-MBP-FGF2) was applied as an artificial matrix to regulate integrin-mediated signalling. 25422949 8 16 theme glycan 1287:1292 arg1 structures 1294:1303 the N-linked glycan structures 1274:1303 the N-linked glycan structures of hMSCs depending on the cell adhesion mechanism using mass spectrometry (MS)-based quantitative techniques 1274:1412 Furthermore, we characterised the N-linked glycan structures of hMSCs depending on the cell adhesion mechanism using mass spectrometry (MS)-based quantitative techniques. 25422949 10 17 theme cell 1771:1774 arg1 fate 1776:1779 stem cell fate 1766:1779 stem cell fate 1766:1779 Thus, the differentiation potential of hMSCs is controlled by the type of adhesion substrate that might provide an idea for the design of biomaterials to control stem cell fate. 25422949 9 18 theme cell 1492:1495 arg1 function 1497:1504 stem cell function 1487:1504 stem cell function 1487:1504 MS analysis revealed that 2,3-sialylated glycans, a potential marker of stem cell function, were more abundant on hMSCs expanded on FN-coated surface than on those expanded on PS-MBP-FGF2. 25422949 0 19 theme cell 76:79 arg1 mechanism 90:98 cell adhesion mechanism 76:98 cell adhesion mechanism 76:98 Control of mesenchymal stem cell phenotype and differentiation depending on cell adhesion mechanism. 25422949 5 20 theme adhering 868:875 arg1 hMSCs 862:866 hMSCs 862:866 hMSCs adhering to PS-MBP-FGF2 862:890 The phosphorylation of focal adhesion kinase, cytoskeletal re-organisation, and cell proliferation were restricted in hMSCs adhering to PS-MBP-FGF2 compared to FN-coated surface. 25422949 7 21 theme adipogenic 1168:1177 arg1 cells 1179:1183 osteogenic and adipogenic cells 1153:1183 osteogenic and adipogenic cells 1153:1183 hMSCs that were expanded on FN-coated surface differentiated into osteogenic and adipogenic cells more readily than those that were expanded on PS-MBP-FGF2. 25422949 3 22 theme mesenchymal-stem 452:467 arg1 behaviour 481:489 human mesenchymal-stem cell (hMSC) behaviour 446:489 human mesenchymal-stem cell (hMSC) behaviour 446:489 We sought to characterise human mesenchymal-stem cell (hMSC) behaviour in response to two different mechanisms of cell adhesion; (i) FGF2-heparan sulphate proteoglycan (HSPG)-mediated adhesion vs. (ii) fibronectin (FN)-integrin-mediated adhesion. 25422949 4 23 theme FN-coated 725:733 arg1 surface 735:741 FN-coated surface 725:741 FN-coated surface 725:741 Heparin inhibited hMSC adhesion to PS-MBP-FGF2 but not to FN-coated surface. 25422949 2 24 theme artificial 360:369 arg1 PS-MBP-FGF2 329:339 a maltose-binding protein (MBP)-linked basic fibroblast growth factor (FGF2)-immobilised polystyrene surface (PS-MBP-FGF2) 219:340 a maltose-binding protein (MBP)-linked basic fibroblast growth factor (FGF2)-immobilised polystyrene surface (PS-MBP-FGF2) 219:340 In this study, a maltose-binding protein (MBP)-linked basic fibroblast growth factor (FGF2)-immobilised polystyrene surface (PS-MBP-FGF2) was applied as an artificial matrix to regulate integrin-mediated signalling. 25422949 2 24 theme artificial 360:369 arg1 matrix 371:376 an artificial matrix 357:376 an artificial matrix 357:376 In this study, a maltose-binding protein (MBP)-linked basic fibroblast growth factor (FGF2)-immobilised polystyrene surface (PS-MBP-FGF2) was applied as an artificial matrix to regulate integrin-mediated signalling. 25422949 7 25 theme osteogenic 1153:1162 arg1 cells 1179:1183 osteogenic and adipogenic cells 1153:1183 osteogenic and adipogenic cells 1153:1183 hMSCs that were expanded on FN-coated surface differentiated into osteogenic and adipogenic cells more readily than those that were expanded on PS-MBP-FGF2. 25422949 8 26 theme adhesion 1336:1343 arg1 mechanism 1345:1353 the cell adhesion mechanism 1327:1353 the cell adhesion mechanism using mass spectrometry (MS)-based quantitative techniques 1327:1412 Furthermore, we characterised the N-linked glycan structures of hMSCs depending on the cell adhesion mechanism using mass spectrometry (MS)-based quantitative techniques. 25422949 5 27 theme focal 767:771 arg1 kinase 782:787 focal adhesion kinase 767:787 focal adhesion kinase 767:787 The phosphorylation of focal adhesion kinase, cytoskeletal re-organisation, and cell proliferation were restricted in hMSCs adhering to PS-MBP-FGF2 compared to FN-coated surface. 25422949 2 28 theme protein 237:243 arg1 factor 282:287 a maltose-binding protein (MBP)-linked basic fibroblast growth factor 219:287 a maltose-binding protein (MBP)-linked basic fibroblast growth factor (FGF2)-immobilised polystyrene surface (PS-MBP-FGF2) 219:340 In this study, a maltose-binding protein (MBP)-linked basic fibroblast growth factor (FGF2)-immobilised polystyrene surface (PS-MBP-FGF2) was applied as an artificial matrix to regulate integrin-mediated signalling. 25422949 2 28 theme protein 237:243 arg1 FGF2 290:293 FGF2 290:293 FGF2 290:293 In this study, a maltose-binding protein (MBP)-linked basic fibroblast growth factor (FGF2)-immobilised polystyrene surface (PS-MBP-FGF2) was applied as an artificial matrix to regulate integrin-mediated signalling. 25422949 11 29 from structure 1808:1816 arg1 membrane 1830:1837 the cell membrane 1821:1837 the cell membrane 1821:1837 Elucidation of the glycan structure on the cell membrane may help characterise hMSC function. 25422949 3 30 theme human 446:450 arg1 behaviour 481:489 human mesenchymal-stem cell (hMSC) behaviour 446:489 human mesenchymal-stem cell (hMSC) behaviour 446:489 We sought to characterise human mesenchymal-stem cell (hMSC) behaviour in response to two different mechanisms of cell adhesion; (i) FGF2-heparan sulphate proteoglycan (HSPG)-mediated adhesion vs. (ii) fibronectin (FN)-integrin-mediated adhesion. 25422949 0 31 theme mesenchymal 11:21 arg1 cell 28:31 mesenchymal stem cell phenotype and differentiation 11:61 cell 28:31 Control of mesenchymal stem cell phenotype and differentiation depending on cell adhesion mechanism. 25422949 9 32 theme FN-coated 1547:1555 arg1 surface 1557:1563 FN-coated surface 1547:1563 FN-coated surface 1547:1563 MS analysis revealed that 2,3-sialylated glycans, a potential marker of stem cell function, were more abundant on hMSCs expanded on FN-coated surface than on those expanded on PS-MBP-FGF2. 25422949 8 33 theme spectrometry 1366:1377 arg1 techniques 1403:1412 mass spectrometry (MS)-based quantitative techniques 1361:1412 mass spectrometry (MS)-based quantitative techniques 1361:1412 Furthermore, we characterised the N-linked glycan structures of hMSCs depending on the cell adhesion mechanism using mass spectrometry (MS)-based quantitative techniques. 25422949 0 34 theme cell 28:31 arg1 Control 0:6 Control 0:6 Control of mesenchymal stem cell phenotype and differentiation 0:61 Control of mesenchymal stem cell phenotype and differentiation depending on cell adhesion mechanism. 25422949 3 35 theme hMSC 475:478 arg1 behaviour 481:489 human mesenchymal-stem cell (hMSC) behaviour 446:489 human mesenchymal-stem cell (hMSC) behaviour 446:489 We sought to characterise human mesenchymal-stem cell (hMSC) behaviour in response to two different mechanisms of cell adhesion; (i) FGF2-heparan sulphate proteoglycan (HSPG)-mediated adhesion vs. (ii) fibronectin (FN)-integrin-mediated adhesion. 25422949 0 36 dep cell 28:31 arg1 phenotype 33:41 phenotype 33:41 phenotype 33:41 Control of mesenchymal stem cell phenotype and differentiation depending on cell adhesion mechanism. 25422949 2 37 theme maltose-binding 221:235 arg1 protein 237:243 a maltose-binding protein 219:243 a maltose-binding protein (MBP)-linked basic fibroblast growth factor (FGF2)-immobilised polystyrene surface (PS-MBP-FGF2) 219:340 In this study, a maltose-binding protein (MBP)-linked basic fibroblast growth factor (FGF2)-immobilised polystyrene surface (PS-MBP-FGF2) was applied as an artificial matrix to regulate integrin-mediated signalling. 25422949 2 37 theme maltose-binding 221:235 arg1 MBP 246:248 MBP 246:248 MBP 246:248 In this study, a maltose-binding protein (MBP)-linked basic fibroblast growth factor (FGF2)-immobilised polystyrene surface (PS-MBP-FGF2) was applied as an artificial matrix to regulate integrin-mediated signalling. 25422949 3 38 theme fibronectin 622:632 arg1 adhesion 657:664 fibronectin (FN)-integrin-mediated adhesion 622:664 fibronectin (FN)-integrin-mediated adhesion 622:664 We sought to characterise human mesenchymal-stem cell (hMSC) behaviour in response to two different mechanisms of cell adhesion; (i) FGF2-heparan sulphate proteoglycan (HSPG)-mediated adhesion vs. (ii) fibronectin (FN)-integrin-mediated adhesion. 25422949 8 39 theme -based 1383:1388 arg1 techniques 1403:1412 mass spectrometry (MS)-based quantitative techniques 1361:1412 mass spectrometry (MS)-based quantitative techniques 1361:1412 Furthermore, we characterised the N-linked glycan structures of hMSCs depending on the cell adhesion mechanism using mass spectrometry (MS)-based quantitative techniques. 25422949 2 40 theme -immobilised 295:306 arg1 PS-MBP-FGF2 329:339 a maltose-binding protein (MBP)-linked basic fibroblast growth factor (FGF2)-immobilised polystyrene surface (PS-MBP-FGF2) 219:340 a maltose-binding protein (MBP)-linked basic fibroblast growth factor (FGF2)-immobilised polystyrene surface (PS-MBP-FGF2) 219:340 In this study, a maltose-binding protein (MBP)-linked basic fibroblast growth factor (FGF2)-immobilised polystyrene surface (PS-MBP-FGF2) was applied as an artificial matrix to regulate integrin-mediated signalling. 25422949 2 40 theme -immobilised 295:306 arg1 matrix 371:376 an artificial matrix 357:376 an artificial matrix 357:376 In this study, a maltose-binding protein (MBP)-linked basic fibroblast growth factor (FGF2)-immobilised polystyrene surface (PS-MBP-FGF2) was applied as an artificial matrix to regulate integrin-mediated signalling. 25422949 5 41 theme kinase 782:787 arg1 phosphorylation 748:762 The phosphorylation 744:762 The phosphorylation of focal adhesion kinase, cytoskeletal re-organisation, and cell proliferation 744:841 The phosphorylation of focal adhesion kinase, cytoskeletal re-organisation, and cell proliferation were restricted in hMSCs adhering to PS-MBP-FGF2 compared to FN-coated surface. 25422949 1 42 theme important 147:155 arg1 issue 157:161 an important issue 144:161 an important issue 144:161 Control of cell-matrix adhesion has become an important issue in the regulation of stem cell function. 25422949 6 43 from expression 1036:1045 arg1 cells 1050:1054 cells 1050:1054 cells expanded on FN-coated surface 1050:1084 Expression of MSC markers, such as CD105, CD90 and CD166, decreased in hMSCs expanded on PS-MBP-FGF2 compared to expression in cells expanded on FN-coated surface. 25422949 11 44 theme cell 1825:1828 arg1 membrane 1830:1837 the cell membrane 1821:1837 the cell membrane 1821:1837 Elucidation of the glycan structure on the cell membrane may help characterise hMSC function. 25422949 9 45 theme MS 1415:1416 arg1 analysis 1418:1425 MS analysis 1415:1425 MS analysis 1415:1425 MS analysis revealed that 2,3-sialylated glycans, a potential marker of stem cell function, were more abundant on hMSCs expanded on FN-coated surface than on those expanded on PS-MBP-FGF2. 25422949 3 46 theme -integrin-mediated 638:655 arg1 adhesion 657:664 fibronectin (FN)-integrin-mediated adhesion 622:664 fibronectin (FN)-integrin-mediated adhesion 622:664 We sought to characterise human mesenchymal-stem cell (hMSC) behaviour in response to two different mechanisms of cell adhesion; (i) FGF2-heparan sulphate proteoglycan (HSPG)-mediated adhesion vs. (ii) fibronectin (FN)-integrin-mediated adhesion. 25422949 10 47 theme adhesion 1678:1685 arg1 substrate 1687:1695 adhesion substrate 1678:1695 adhesion substrate that might provide an idea for the design of biomaterials to control stem cell fate 1678:1779 Thus, the differentiation potential of hMSCs is controlled by the type of adhesion substrate that might provide an idea for the design of biomaterials to control stem cell fate. 25422949 1 48 theme function 194:201 arg1 regulation 170:179 the regulation 166:179 the regulation of stem cell function 166:201 Control of cell-matrix adhesion has become an important issue in the regulation of stem cell function. 25422949 3 49 theme FN 635:636 arg1 adhesion 657:664 fibronectin (FN)-integrin-mediated adhesion 622:664 fibronectin (FN)-integrin-mediated adhesion 622:664 We sought to characterise human mesenchymal-stem cell (hMSC) behaviour in response to two different mechanisms of cell adhesion; (i) FGF2-heparan sulphate proteoglycan (HSPG)-mediated adhesion vs. (ii) fibronectin (FN)-integrin-mediated adhesion. 25422949 2 50 theme fibroblast 264:273 arg1 factor 282:287 a maltose-binding protein (MBP)-linked basic fibroblast growth factor 219:287 a maltose-binding protein (MBP)-linked basic fibroblast growth factor (FGF2)-immobilised polystyrene surface (PS-MBP-FGF2) 219:340 In this study, a maltose-binding protein (MBP)-linked basic fibroblast growth factor (FGF2)-immobilised polystyrene surface (PS-MBP-FGF2) was applied as an artificial matrix to regulate integrin-mediated signalling. 25422949 2 50 theme fibroblast 264:273 arg1 FGF2 290:293 FGF2 290:293 FGF2 290:293 In this study, a maltose-binding protein (MBP)-linked basic fibroblast growth factor (FGF2)-immobilised polystyrene surface (PS-MBP-FGF2) was applied as an artificial matrix to regulate integrin-mediated signalling. 25422949 11 51 from Elucidation 1782:1792 arg1 membrane 1830:1837 the cell membrane 1821:1837 the cell membrane 1821:1837 Elucidation of the glycan structure on the cell membrane may help characterise hMSC function. 25422949 2 52 theme surface 320:326 arg1 PS-MBP-FGF2 329:339 a maltose-binding protein (MBP)-linked basic fibroblast growth factor (FGF2)-immobilised polystyrene surface (PS-MBP-FGF2) 219:340 a maltose-binding protein (MBP)-linked basic fibroblast growth factor (FGF2)-immobilised polystyrene surface (PS-MBP-FGF2) 219:340 In this study, a maltose-binding protein (MBP)-linked basic fibroblast growth factor (FGF2)-immobilised polystyrene surface (PS-MBP-FGF2) was applied as an artificial matrix to regulate integrin-mediated signalling. 25422949 2 52 theme surface 320:326 arg1 matrix 371:376 an artificial matrix 357:376 an artificial matrix 357:376 In this study, a maltose-binding protein (MBP)-linked basic fibroblast growth factor (FGF2)-immobilised polystyrene surface (PS-MBP-FGF2) was applied as an artificial matrix to regulate integrin-mediated signalling. 25422949 7 53 theme FN-coated 1115:1123 arg1 surface 1125:1131 FN-coated surface 1115:1131 FN-coated surface 1115:1131 hMSCs that were expanded on FN-coated surface differentiated into osteogenic and adipogenic cells more readily than those that were expanded on PS-MBP-FGF2. 25422949 2 54 theme -linked 250:256 arg1 factor 282:287 a maltose-binding protein (MBP)-linked basic fibroblast growth factor 219:287 a maltose-binding protein (MBP)-linked basic fibroblast growth factor (FGF2)-immobilised polystyrene surface (PS-MBP-FGF2) 219:340 In this study, a maltose-binding protein (MBP)-linked basic fibroblast growth factor (FGF2)-immobilised polystyrene surface (PS-MBP-FGF2) was applied as an artificial matrix to regulate integrin-mediated signalling. 25422949 2 54 theme -linked 250:256 arg1 FGF2 290:293 FGF2 290:293 FGF2 290:293 In this study, a maltose-binding protein (MBP)-linked basic fibroblast growth factor (FGF2)-immobilised polystyrene surface (PS-MBP-FGF2) was applied as an artificial matrix to regulate integrin-mediated signalling. 25422949 5 55 theme proliferation 829:841 arg1 phosphorylation 748:762 The phosphorylation 744:762 The phosphorylation of focal adhesion kinase, cytoskeletal re-organisation, and cell proliferation 744:841 The phosphorylation of focal adhesion kinase, cytoskeletal re-organisation, and cell proliferation were restricted in hMSCs adhering to PS-MBP-FGF2 compared to FN-coated surface. 25422949 2 56 theme factor 282:287 arg1 PS-MBP-FGF2 329:339 a maltose-binding protein (MBP)-linked basic fibroblast growth factor (FGF2)-immobilised polystyrene surface (PS-MBP-FGF2) 219:340 a maltose-binding protein (MBP)-linked basic fibroblast growth factor (FGF2)-immobilised polystyrene surface (PS-MBP-FGF2) 219:340 In this study, a maltose-binding protein (MBP)-linked basic fibroblast growth factor (FGF2)-immobilised polystyrene surface (PS-MBP-FGF2) was applied as an artificial matrix to regulate integrin-mediated signalling. 25422949 2 56 theme factor 282:287 arg1 matrix 371:376 an artificial matrix 357:376 an artificial matrix 357:376 In this study, a maltose-binding protein (MBP)-linked basic fibroblast growth factor (FGF2)-immobilised polystyrene surface (PS-MBP-FGF2) was applied as an artificial matrix to regulate integrin-mediated signalling. 25422949 3 57 dep proteoglycan 575:586 arg1 i 550:550 i 550:550 i 550:550 We sought to characterise human mesenchymal-stem cell (hMSC) behaviour in response to two different mechanisms of cell adhesion; (i) FGF2-heparan sulphate proteoglycan (HSPG)-mediated adhesion vs. (ii) fibronectin (FN)-integrin-mediated adhesion. 25422949 6 58 theme MSC 937:939 arg1 CD105 958:962 CD105 958:962 CD105 958:962 Expression of MSC markers, such as CD105, CD90 and CD166, decreased in hMSCs expanded on PS-MBP-FGF2 compared to expression in cells expanded on FN-coated surface. 25422949 6 58 theme MSC 937:939 arg1 CD166 974:978 CD166 974:978 CD166 974:978 Expression of MSC markers, such as CD105, CD90 and CD166, decreased in hMSCs expanded on PS-MBP-FGF2 compared to expression in cells expanded on FN-coated surface. 25422949 6 58 theme MSC 937:939 arg1 markers 941:947 MSC markers 937:947 MSC markers 937:947 Expression of MSC markers, such as CD105, CD90 and CD166, decreased in hMSCs expanded on PS-MBP-FGF2 compared to expression in cells expanded on FN-coated surface. 25422949 6 58 theme MSC 937:939 arg1 CD90 965:968 CD90 965:968 CD90 965:968 Expression of MSC markers, such as CD105, CD90 and CD166, decreased in hMSCs expanded on PS-MBP-FGF2 compared to expression in cells expanded on FN-coated surface. 25422949 11 59 theme structure 1808:1816 arg1 Elucidation 1782:1792 Elucidation 1782:1792 Elucidation of the glycan structure on the cell membrane 1782:1837 Elucidation of the glycan structure on the cell membrane may help characterise hMSC function. 25422949 11 60 theme glycan 1801:1806 arg1 structure 1808:1816 the glycan structure 1797:1816 the glycan structure on the cell membrane 1797:1837 Elucidation of the glycan structure on the cell membrane may help characterise hMSC function. 25422949 3 61 theme FGF2-heparan 553:564 arg1 HSPG 589:592 HSPG 589:592 HSPG 589:592 We sought to characterise human mesenchymal-stem cell (hMSC) behaviour in response to two different mechanisms of cell adhesion; (i) FGF2-heparan sulphate proteoglycan (HSPG)-mediated adhesion vs. (ii) fibronectin (FN)-integrin-mediated adhesion. 25422949 3 61 theme FGF2-heparan 553:564 arg1 proteoglycan 575:586 (i) FGF2-heparan sulphate proteoglycan 549:586 (i) FGF2-heparan sulphate proteoglycan (HSPG)-mediated adhesion 549:611 We sought to characterise human mesenchymal-stem cell (hMSC) behaviour in response to two different mechanisms of cell adhesion; (i) FGF2-heparan sulphate proteoglycan (HSPG)-mediated adhesion vs. (ii) fibronectin (FN)-integrin-mediated adhesion. 25422949 5 62 theme re-organisation 803:817 arg1 phosphorylation 748:762 The phosphorylation 744:762 The phosphorylation of focal adhesion kinase, cytoskeletal re-organisation, and cell proliferation 744:841 The phosphorylation of focal adhesion kinase, cytoskeletal re-organisation, and cell proliferation were restricted in hMSCs adhering to PS-MBP-FGF2 compared to FN-coated surface. 25422949 1 63 theme cell-matrix 112:122 arg1 adhesion 124:131 cell-matrix adhesion 112:131 cell-matrix adhesion 112:131 Control of cell-matrix adhesion has become an important issue in the regulation of stem cell function. 25422949 9 64 gly 2,3-sialylated 1441:1454 arg1 marker 1477:1482 a potential marker 1465:1482 a potential marker of stem cell function 1465:1504 MS analysis revealed that 2,3-sialylated glycans, a potential marker of stem cell function, were more abundant on hMSCs expanded on FN-coated surface than on those expanded on PS-MBP-FGF2. 25422949 9 64 gly 2,3-sialylated 1441:1454 arg1 glycans 1456:1462 2,3-sialylated glycans 1441:1462 2,3-sialylated glycans 1441:1462 MS analysis revealed that 2,3-sialylated glycans, a potential marker of stem cell function, were more abundant on hMSCs expanded on FN-coated surface than on those expanded on PS-MBP-FGF2. 25422949 3 65 dep mechanisms 520:529 arg1 response 494:501 response 494:501 response 494:501 We sought to characterise human mesenchymal-stem cell (hMSC) behaviour in response to two different mechanisms of cell adhesion; (i) FGF2-heparan sulphate proteoglycan (HSPG)-mediated adhesion vs. (ii) fibronectin (FN)-integrin-mediated adhesion. 25422949 3 65 dep mechanisms 520:529 arg1 adhesion 604:611 (i) FGF2-heparan sulphate proteoglycan (HSPG)-mediated adhesion 549:611 (i) FGF2-heparan sulphate proteoglycan (HSPG)-mediated adhesion 549:611 We sought to characterise human mesenchymal-stem cell (hMSC) behaviour in response to two different mechanisms of cell adhesion; (i) FGF2-heparan sulphate proteoglycan (HSPG)-mediated adhesion vs. (ii) fibronectin (FN)-integrin-mediated adhesion. 25422949 3 66 theme cell 534:537 arg1 adhesion 539:546 cell adhesion 534:546 cell adhesion 534:546 We sought to characterise human mesenchymal-stem cell (hMSC) behaviour in response to two different mechanisms of cell adhesion; (i) FGF2-heparan sulphate proteoglycan (HSPG)-mediated adhesion vs. (ii) fibronectin (FN)-integrin-mediated adhesion. 25422949 3 67 theme cell 469:472 arg1 behaviour 481:489 human mesenchymal-stem cell (hMSC) behaviour 446:489 human mesenchymal-stem cell (hMSC) behaviour 446:489 We sought to characterise human mesenchymal-stem cell (hMSC) behaviour in response to two different mechanisms of cell adhesion; (i) FGF2-heparan sulphate proteoglycan (HSPG)-mediated adhesion vs. (ii) fibronectin (FN)-integrin-mediated adhesion. 25422949 3 68 theme proteoglycan 575:586 arg1 adhesion 604:611 (i) FGF2-heparan sulphate proteoglycan (HSPG)-mediated adhesion 549:611 (i) FGF2-heparan sulphate proteoglycan (HSPG)-mediated adhesion 549:611 We sought to characterise human mesenchymal-stem cell (hMSC) behaviour in response to two different mechanisms of cell adhesion; (i) FGF2-heparan sulphate proteoglycan (HSPG)-mediated adhesion vs. (ii) fibronectin (FN)-integrin-mediated adhesion. 25422949 1 69 theme cell 189:192 arg1 function 194:201 stem cell function 184:201 stem cell function 184:201 Control of cell-matrix adhesion has become an important issue in the regulation of stem cell function. 25422949 9 70 theme stem 1487:1490 arg1 function 1497:1504 stem cell function 1487:1504 stem cell function 1487:1504 MS analysis revealed that 2,3-sialylated glycans, a potential marker of stem cell function, were more abundant on hMSCs expanded on FN-coated surface than on those expanded on PS-MBP-FGF2. 25422949 8 71 theme N-linked 1278:1285 arg1 structures 1294:1303 the N-linked glycan structures 1274:1303 the N-linked glycan structures of hMSCs depending on the cell adhesion mechanism using mass spectrometry (MS)-based quantitative techniques 1274:1412 Furthermore, we characterised the N-linked glycan structures of hMSCs depending on the cell adhesion mechanism using mass spectrometry (MS)-based quantitative techniques. 25422949 0 72 theme adhesion 81:88 arg1 mechanism 90:98 cell adhesion mechanism 76:98 cell adhesion mechanism 76:98 Control of mesenchymal stem cell phenotype and differentiation depending on cell adhesion mechanism. 25422949 9 73 theme function 1497:1504 arg1 marker 1477:1482 a potential marker 1465:1482 a potential marker of stem cell function 1465:1504 MS analysis revealed that 2,3-sialylated glycans, a potential marker of stem cell function, were more abundant on hMSCs expanded on FN-coated surface than on those expanded on PS-MBP-FGF2. 25422949 9 73 theme function 1497:1504 arg1 glycans 1456:1462 2,3-sialylated glycans 1441:1462 2,3-sialylated glycans 1441:1462 MS analysis revealed that 2,3-sialylated glycans, a potential marker of stem cell function, were more abundant on hMSCs expanded on FN-coated surface than on those expanded on PS-MBP-FGF2. 25422949 2 74 theme growth 275:280 arg1 factor 282:287 a maltose-binding protein (MBP)-linked basic fibroblast growth factor 219:287 a maltose-binding protein (MBP)-linked basic fibroblast growth factor (FGF2)-immobilised polystyrene surface (PS-MBP-FGF2) 219:340 In this study, a maltose-binding protein (MBP)-linked basic fibroblast growth factor (FGF2)-immobilised polystyrene surface (PS-MBP-FGF2) was applied as an artificial matrix to regulate integrin-mediated signalling. 25422949 2 74 theme growth 275:280 arg1 FGF2 290:293 FGF2 290:293 FGF2 290:293 In this study, a maltose-binding protein (MBP)-linked basic fibroblast growth factor (FGF2)-immobilised polystyrene surface (PS-MBP-FGF2) was applied as an artificial matrix to regulate integrin-mediated signalling. 25422949 8 75 theme hMSCs 1308:1312 arg1 structures 1294:1303 the N-linked glycan structures 1274:1303 the N-linked glycan structures of hMSCs depending on the cell adhesion mechanism using mass spectrometry (MS)-based quantitative techniques 1274:1412 Furthermore, we characterised the N-linked glycan structures of hMSCs depending on the cell adhesion mechanism using mass spectrometry (MS)-based quantitative techniques. 25422949 5 76 theme cytoskeletal 790:801 arg1 re-organisation 803:817 cytoskeletal re-organisation 790:817 cytoskeletal re-organisation 790:817 The phosphorylation of focal adhesion kinase, cytoskeletal re-organisation, and cell proliferation were restricted in hMSCs adhering to PS-MBP-FGF2 compared to FN-coated surface. 25422949 11 77 theme hMSC 1861:1864 arg1 function 1866:1873 hMSC function 1861:1873 hMSC function 1861:1873 Elucidation of the glycan structure on the cell membrane may help characterise hMSC function. 25422949 8 78 from structures 1294:1303 arg1 mechanism 1345:1353 the cell adhesion mechanism 1327:1353 the cell adhesion mechanism using mass spectrometry (MS)-based quantitative techniques 1327:1412 Furthermore, we characterised the N-linked glycan structures of hMSCs depending on the cell adhesion mechanism using mass spectrometry (MS)-based quantitative techniques. 25422949 5 79 theme FN-coated 904:912 arg1 surface 914:920 FN-coated surface 904:920 FN-coated surface 904:920 The phosphorylation of focal adhesion kinase, cytoskeletal re-organisation, and cell proliferation were restricted in hMSCs adhering to PS-MBP-FGF2 compared to FN-coated surface. 25422949 4 80 theme hMSC 685:688 arg1 adhesion 690:697 hMSC adhesion 685:697 hMSC adhesion 685:697 Heparin inhibited hMSC adhesion to PS-MBP-FGF2 but not to FN-coated surface. 25422949 0 81 theme stem 23:26 arg1 cell 28:31 mesenchymal stem cell phenotype and differentiation 11:61 cell 28:31 Control of mesenchymal stem cell phenotype and differentiation depending on cell adhesion mechanism. 25422949 11 82 from membrane 1830:1837 arg1 Elucidation 1782:1792 Elucidation 1782:1792 Elucidation of the glycan structure on the cell membrane 1782:1837 Elucidation of the glycan structure on the cell membrane may help characterise hMSC function. 25422949 10 83 theme stem 1766:1769 arg1 fate 1776:1779 stem cell fate 1766:1779 stem cell fate 1766:1779 Thus, the differentiation potential of hMSCs is controlled by the type of adhesion substrate that might provide an idea for the design of biomaterials to control stem cell fate. 25422949 10 84 theme hMSCs 1643:1647 arg1 potential 1630:1638 the differentiation potential 1610:1638 the differentiation potential of hMSCs 1610:1647 Thus, the differentiation potential of hMSCs is controlled by the type of adhesion substrate that might provide an idea for the design of biomaterials to control stem cell fate. 25422949 10 85 theme differentiation 1614:1628 arg1 potential 1630:1638 the differentiation potential 1610:1638 the differentiation potential of hMSCs 1610:1647 Thus, the differentiation potential of hMSCs is controlled by the type of adhesion substrate that might provide an idea for the design of biomaterials to control stem cell fate. 25422949 3 86 theme -mediated 594:602 arg1 adhesion 604:611 (i) FGF2-heparan sulphate proteoglycan (HSPG)-mediated adhesion 549:611 (i) FGF2-heparan sulphate proteoglycan (HSPG)-mediated adhesion 549:611 We sought to characterise human mesenchymal-stem cell (hMSC) behaviour in response to two different mechanisms of cell adhesion; (i) FGF2-heparan sulphate proteoglycan (HSPG)-mediated adhesion vs. (ii) fibronectin (FN)-integrin-mediated adhesion. 25422949 8 87 theme mass 1361:1364 arg1 MS 1380:1381 MS 1380:1381 MS 1380:1381 Furthermore, we characterised the N-linked glycan structures of hMSCs depending on the cell adhesion mechanism using mass spectrometry (MS)-based quantitative techniques. 25422949 8 87 theme mass 1361:1364 arg1 spectrometry 1366:1377 mass spectrometry 1361:1377 mass spectrometry (MS)-based quantitative techniques 1361:1412 Furthermore, we characterised the N-linked glycan structures of hMSCs depending on the cell adhesion mechanism using mass spectrometry (MS)-based quantitative techniques. 25422949 0 88 theme differentiation 47:61 arg1 Control 0:6 Control 0:6 Control of mesenchymal stem cell phenotype and differentiation 0:61 Control of mesenchymal stem cell phenotype and differentiation depending on cell adhesion mechanism. 25422949 2 89 theme polystyrene 308:318 arg1 PS-MBP-FGF2 329:339 a maltose-binding protein (MBP)-linked basic fibroblast growth factor (FGF2)-immobilised polystyrene surface (PS-MBP-FGF2) 219:340 a maltose-binding protein (MBP)-linked basic fibroblast growth factor (FGF2)-immobilised polystyrene surface (PS-MBP-FGF2) 219:340 In this study, a maltose-binding protein (MBP)-linked basic fibroblast growth factor (FGF2)-immobilised polystyrene surface (PS-MBP-FGF2) was applied as an artificial matrix to regulate integrin-mediated signalling. 25422949 2 89 theme polystyrene 308:318 arg1 matrix 371:376 an artificial matrix 357:376 an artificial matrix 357:376 In this study, a maltose-binding protein (MBP)-linked basic fibroblast growth factor (FGF2)-immobilised polystyrene surface (PS-MBP-FGF2) was applied as an artificial matrix to regulate integrin-mediated signalling. 25422949 6 90 theme FN-coated 1068:1076 arg1 surface 1078:1084 FN-coated surface 1068:1084 FN-coated surface 1068:1084 Expression of MSC markers, such as CD105, CD90 and CD166, decreased in hMSCs expanded on PS-MBP-FGF2 compared to expression in cells expanded on FN-coated surface. 25422949 3 91 dep adhesion 604:611 arg1 ii 618:619 ii 618:619 ii 618:619 We sought to characterise human mesenchymal-stem cell (hMSC) behaviour in response to two different mechanisms of cell adhesion; (i) FGF2-heparan sulphate proteoglycan (HSPG)-mediated adhesion vs. (ii) fibronectin (FN)-integrin-mediated adhesion. 25422949 3 91 dep adhesion 604:611 arg1 adhesion 657:664 fibronectin (FN)-integrin-mediated adhesion 622:664 fibronectin (FN)-integrin-mediated adhesion 622:664 We sought to characterise human mesenchymal-stem cell (hMSC) behaviour in response to two different mechanisms of cell adhesion; (i) FGF2-heparan sulphate proteoglycan (HSPG)-mediated adhesion vs. (ii) fibronectin (FN)-integrin-mediated adhesion. 25422949 8 92 theme quantitative 1390:1401 arg1 techniques 1403:1412 mass spectrometry (MS)-based quantitative techniques 1361:1412 mass spectrometry (MS)-based quantitative techniques 1361:1412 Furthermore, we characterised the N-linked glycan structures of hMSCs depending on the cell adhesion mechanism using mass spectrometry (MS)-based quantitative techniques. 25422949 10 93 theme substrate 1687:1695 arg1 type 1670:1673 the type 1666:1673 the type of adhesion substrate that might provide an idea for the design of biomaterials to control stem cell fate 1666:1779 Thus, the differentiation potential of hMSCs is controlled by the type of adhesion substrate that might provide an idea for the design of biomaterials to control stem cell fate. 25280556 6 0 theme RNA 1224:1226 arg1 promoters 1228:1236 two subgenomic RNA promoters 1209:1236 two subgenomic RNA promoters 1209:1236 To demonstrate co-expression and functionality of two independent proteins, we cloned the sequences of the Pfs48/45 protein of Plasmodium falciparum and endoglycosidase F (PNGase F) from Flavobacterium meningosepticum into the miniBYV vector under the control of two subgenomic RNA promoters. 25280556 6 1 theme Pfs48/45 1053:1060 arg1 protein 1062:1068 the Pfs48/45 protein 1049:1068 the Pfs48/45 protein of Plasmodium falciparum and endoglycosidase F (PNGase F) 1049:1126 To demonstrate co-expression and functionality of two independent proteins, we cloned the sequences of the Pfs48/45 protein of Plasmodium falciparum and endoglycosidase F (PNGase F) from Flavobacterium meningosepticum into the miniBYV vector under the control of two subgenomic RNA promoters. 25280556 4 2 theme genetic 558:564 arg1 stability 566:574 genetic stability 558:574 genetic stability 558:574 This BYV vector maintained genetic stability during systemic spread throughout the host plant, Nicotiana benthamiana. 25280556 0 3 theme proteins 82:89 arg1 co-expression 52:64 co-expression 52:64 co-expression of heterologous proteins 52:89 Development of a single-replicon miniBYV vector for co-expression of heterologous proteins. 25280556 1 4 theme monoclonal 169:178 arg1 antibodies 180:189 monoclonal antibodies 169:189 monoclonal antibodies 169:189 In planta production of recombinant proteins, including vaccine antigens and monoclonal antibodies, continues gaining acceptance. 25280556 3 5 theme single-replicon 354:368 arg1 based 377:381 a single-replicon vector based 352:381 a single-replicon vector based on beet yellows virus (BYV) that enables co-delivery of two target genes into the same host cell, resulting in transient expression of each target 352:528 Here, we have developed a single-replicon vector based on beet yellows virus (BYV) that enables co-delivery of two target genes into the same host cell, resulting in transient expression of each target. 25280556 7 6 theme Pfs48/45 1347:1354 arg1 accumulation 1311:1322 accumulation 1311:1322 accumulation of biologically active Pfs48/45 that was devoid of N-linked glycosylation and had correct conformation and epitope display 1311:1445 Agroinfiltration of N. benthamiana with this miniBYV vector resulted in accumulation of biologically active Pfs48/45 that was devoid of N-linked glycosylation and had correct conformation and epitope display. 25280556 2 7 theme higher 294:299 arg1 performance 301:311 higher performance 294:311 higher performance 294:311 With the broadening range of target proteins, the need for vectors with higher performance is increasing. 25280556 7 8 theme epitope 1431:1437 arg1 display 1439:1445 epitope display 1431:1445 epitope display 1431:1445 Agroinfiltration of N. benthamiana with this miniBYV vector resulted in accumulation of biologically active Pfs48/45 that was devoid of N-linked glycosylation and had correct conformation and epitope display. 25280556 3 9 theme vector 370:375 arg1 based 377:381 a single-replicon vector based 352:381 a single-replicon vector based on beet yellows virus (BYV) that enables co-delivery of two target genes into the same host cell, resulting in transient expression of each target 352:528 Here, we have developed a single-replicon vector based on beet yellows virus (BYV) that enables co-delivery of two target genes into the same host cell, resulting in transient expression of each target. 25280556 3 10 from based 377:381 arg1 BYV 406:408 BYV 406:408 BYV 406:408 Here, we have developed a single-replicon vector based on beet yellows virus (BYV) that enables co-delivery of two target genes into the same host cell, resulting in transient expression of each target. 25280556 3 10 from based 377:381 arg1 virus 399:403 beet yellows virus 386:403 beet yellows virus (BYV) 386:409 Here, we have developed a single-replicon vector based on beet yellows virus (BYV) that enables co-delivery of two target genes into the same host cell, resulting in transient expression of each target. 25280556 5 11 theme fresh 927:931 arg1 tissue 938:943 fresh leaf tissue 927:943 fresh leaf tissue 927:943 Furthermore, we have engineered a miniBYV vector carrying the sequences encoding heavy and light chains of a monoclonal antibody (mAb) against protective antigen (PA) of Bacillius anthracis, and achieved the expression of the full-length functional anti-PA mAb at ~300 mg/kg of fresh leaf tissue. 25280556 3 12 theme target 523:528 arg1 expression 504:513 transient expression 494:513 transient expression of each target 494:528 Here, we have developed a single-replicon vector based on beet yellows virus (BYV) that enables co-delivery of two target genes into the same host cell, resulting in transient expression of each target. 25280556 5 13 theme anti-PA 898:904 arg1 mAb 906:908 the full-length functional anti-PA mAb 871:908 the full-length functional anti-PA mAb 871:908 Furthermore, we have engineered a miniBYV vector carrying the sequences encoding heavy and light chains of a monoclonal antibody (mAb) against protective antigen (PA) of Bacillius anthracis, and achieved the expression of the full-length functional anti-PA mAb at ~300 mg/kg of fresh leaf tissue. 25280556 5 14 theme heavy 730:734 arg1 chains 746:751 heavy and light chains 730:751 heavy and light chains of a monoclonal antibody (mAb) against protective antigen (PA) of Bacillius anthracis 730:837 Furthermore, we have engineered a miniBYV vector carrying the sequences encoding heavy and light chains of a monoclonal antibody (mAb) against protective antigen (PA) of Bacillius anthracis, and achieved the expression of the full-length functional anti-PA mAb at ~300 mg/kg of fresh leaf tissue. 25280556 1 15 theme recombinant 116:126 arg1 antigens 156:163 vaccine antigens 148:163 vaccine antigens 148:163 In planta production of recombinant proteins, including vaccine antigens and monoclonal antibodies, continues gaining acceptance. 25280556 1 15 theme recombinant 116:126 arg1 antibodies 180:189 monoclonal antibodies 169:189 monoclonal antibodies 169:189 In planta production of recombinant proteins, including vaccine antigens and monoclonal antibodies, continues gaining acceptance. 25280556 1 15 theme recombinant 116:126 arg1 proteins 128:135 recombinant proteins 116:135 recombinant proteins 116:135 In planta production of recombinant proteins, including vaccine antigens and monoclonal antibodies, continues gaining acceptance. 25280556 6 16 theme promoters 1228:1236 arg1 control 1198:1204 the control 1194:1204 the control of two subgenomic RNA promoters 1194:1236 To demonstrate co-expression and functionality of two independent proteins, we cloned the sequences of the Pfs48/45 protein of Plasmodium falciparum and endoglycosidase F (PNGase F) from Flavobacterium meningosepticum into the miniBYV vector under the control of two subgenomic RNA promoters. 25280556 7 17 theme miniBYV 1284:1290 arg1 vector 1292:1297 this miniBYV vector 1279:1297 this miniBYV vector 1279:1297 Agroinfiltration of N. benthamiana with this miniBYV vector resulted in accumulation of biologically active Pfs48/45 that was devoid of N-linked glycosylation and had correct conformation and epitope display. 25280556 5 18 theme leaf 933:936 arg1 tissue 938:943 fresh leaf tissue 927:943 fresh leaf tissue 927:943 Furthermore, we have engineered a miniBYV vector carrying the sequences encoding heavy and light chains of a monoclonal antibody (mAb) against protective antigen (PA) of Bacillius anthracis, and achieved the expression of the full-length functional anti-PA mAb at ~300 mg/kg of fresh leaf tissue. 25280556 7 19 link N-linked 1375:1382 arg1 glycosylation 1384:1396 N-linked glycosylation 1375:1396 N-linked glycosylation 1375:1396 Agroinfiltration of N. benthamiana with this miniBYV vector resulted in accumulation of biologically active Pfs48/45 that was devoid of N-linked glycosylation and had correct conformation and epitope display. 25280556 5 20 theme monoclonal 758:767 arg1 mAb 779:781 mAb 779:781 mAb 779:781 Furthermore, we have engineered a miniBYV vector carrying the sequences encoding heavy and light chains of a monoclonal antibody (mAb) against protective antigen (PA) of Bacillius anthracis, and achieved the expression of the full-length functional anti-PA mAb at ~300 mg/kg of fresh leaf tissue. 25280556 5 20 theme monoclonal 758:767 arg1 antibody 769:776 a monoclonal antibody 756:776 a monoclonal antibody (mAb) against protective antigen (PA) of Bacillius anthracis 756:837 Furthermore, we have engineered a miniBYV vector carrying the sequences encoding heavy and light chains of a monoclonal antibody (mAb) against protective antigen (PA) of Bacillius anthracis, and achieved the expression of the full-length functional anti-PA mAb at ~300 mg/kg of fresh leaf tissue. 25280556 5 21 theme tissue 938:943 arg1 mg/kg 918:922 ~300 mg/kg 913:922 ~300 mg/kg of fresh leaf tissue 913:943 Furthermore, we have engineered a miniBYV vector carrying the sequences encoding heavy and light chains of a monoclonal antibody (mAb) against protective antigen (PA) of Bacillius anthracis, and achieved the expression of the full-length functional anti-PA mAb at ~300 mg/kg of fresh leaf tissue. 25280556 6 22 from meningosepticum 1148:1162 arg1 sequences 1036:1044 the sequences 1032:1044 the sequences of the Pfs48/45 protein of Plasmodium falciparum and endoglycosidase F (PNGase F) from Flavobacterium meningosepticum 1032:1162 To demonstrate co-expression and functionality of two independent proteins, we cloned the sequences of the Pfs48/45 protein of Plasmodium falciparum and endoglycosidase F (PNGase F) from Flavobacterium meningosepticum into the miniBYV vector under the control of two subgenomic RNA promoters. 25280556 5 23 theme anthracis 829:837 arg1 PA 812:813 PA 812:813 PA 812:813 Furthermore, we have engineered a miniBYV vector carrying the sequences encoding heavy and light chains of a monoclonal antibody (mAb) against protective antigen (PA) of Bacillius anthracis, and achieved the expression of the full-length functional anti-PA mAb at ~300 mg/kg of fresh leaf tissue. 25280556 5 23 theme anthracis 829:837 arg1 antigen 803:809 protective antigen 792:809 protective antigen (PA) of Bacillius anthracis 792:837 Furthermore, we have engineered a miniBYV vector carrying the sequences encoding heavy and light chains of a monoclonal antibody (mAb) against protective antigen (PA) of Bacillius anthracis, and achieved the expression of the full-length functional anti-PA mAb at ~300 mg/kg of fresh leaf tissue. 25280556 3 24 theme beet 386:389 arg1 BYV 406:408 BYV 406:408 BYV 406:408 Here, we have developed a single-replicon vector based on beet yellows virus (BYV) that enables co-delivery of two target genes into the same host cell, resulting in transient expression of each target. 25280556 3 24 theme beet 386:389 arg1 virus 399:403 beet yellows virus 386:403 beet yellows virus (BYV) 386:409 Here, we have developed a single-replicon vector based on beet yellows virus (BYV) that enables co-delivery of two target genes into the same host cell, resulting in transient expression of each target. 25280556 8 25 theme active 1557:1562 arg1 proteins 1576:1583 two functionally active recombinant proteins 1540:1583 two functionally active recombinant proteins within the same host cell 1540:1609 Overall, our findings demonstrate that the new BYV-based vector is capable of co-expressing two functionally active recombinant proteins within the same host cell. 25280556 6 26 theme subgenomic 1213:1222 arg1 promoters 1228:1236 two subgenomic RNA promoters 1209:1236 two subgenomic RNA promoters 1209:1236 To demonstrate co-expression and functionality of two independent proteins, we cloned the sequences of the Pfs48/45 protein of Plasmodium falciparum and endoglycosidase F (PNGase F) from Flavobacterium meningosepticum into the miniBYV vector under the control of two subgenomic RNA promoters. 25280556 5 27 theme light 740:744 arg1 chains 746:751 heavy and light chains 730:751 heavy and light chains of a monoclonal antibody (mAb) against protective antigen (PA) of Bacillius anthracis 730:837 Furthermore, we have engineered a miniBYV vector carrying the sequences encoding heavy and light chains of a monoclonal antibody (mAb) against protective antigen (PA) of Bacillius anthracis, and achieved the expression of the full-length functional anti-PA mAb at ~300 mg/kg of fresh leaf tissue. 25280556 5 28 theme mAb 906:908 arg1 expression 857:866 the expression 853:866 the expression of the full-length functional anti-PA mAb 853:908 Furthermore, we have engineered a miniBYV vector carrying the sequences encoding heavy and light chains of a monoclonal antibody (mAb) against protective antigen (PA) of Bacillius anthracis, and achieved the expression of the full-length functional anti-PA mAb at ~300 mg/kg of fresh leaf tissue. 25280556 3 29 theme yellows 391:397 arg1 BYV 406:408 BYV 406:408 BYV 406:408 Here, we have developed a single-replicon vector based on beet yellows virus (BYV) that enables co-delivery of two target genes into the same host cell, resulting in transient expression of each target. 25280556 3 29 theme yellows 391:397 arg1 virus 399:403 beet yellows virus 386:403 beet yellows virus (BYV) 386:409 Here, we have developed a single-replicon vector based on beet yellows virus (BYV) that enables co-delivery of two target genes into the same host cell, resulting in transient expression of each target. 25280556 6 30 theme PNGase 1118:1123 arg1 F 1115:1115 endoglycosidase F 1099:1115 endoglycosidase F (PNGase F) 1099:1126 To demonstrate co-expression and functionality of two independent proteins, we cloned the sequences of the Pfs48/45 protein of Plasmodium falciparum and endoglycosidase F (PNGase F) from Flavobacterium meningosepticum into the miniBYV vector under the control of two subgenomic RNA promoters. 25280556 6 30 theme PNGase 1118:1123 arg1 F 1125:1125 PNGase F 1118:1125 PNGase F 1118:1125 To demonstrate co-expression and functionality of two independent proteins, we cloned the sequences of the Pfs48/45 protein of Plasmodium falciparum and endoglycosidase F (PNGase F) from Flavobacterium meningosepticum into the miniBYV vector under the control of two subgenomic RNA promoters. 25280556 1 31 theme gaining 202:208 arg1 acceptance 210:219 gaining acceptance 202:219 gaining acceptance 202:219 In planta production of recombinant proteins, including vaccine antigens and monoclonal antibodies, continues gaining acceptance. 25280556 0 32 theme single-replicon 17:31 arg1 vector 41:46 a single-replicon miniBYV vector 15:46 a single-replicon miniBYV vector for co-expression of heterologous proteins 15:89 Development of a single-replicon miniBYV vector for co-expression of heterologous proteins. 25280556 5 33 contain carrying 698:705 arg1 vector 691:696 a miniBYV vector 681:696 a miniBYV vector carrying the sequences encoding heavy and light chains of a monoclonal antibody (mAb) against protective antigen (PA) of Bacillius anthracis 681:837 Furthermore, we have engineered a miniBYV vector carrying the sequences encoding heavy and light chains of a monoclonal antibody (mAb) against protective antigen (PA) of Bacillius anthracis, and achieved the expression of the full-length functional anti-PA mAb at ~300 mg/kg of fresh leaf tissue. 25280556 5 33 contain carrying 698:705 arg2 sequences 711:719 the sequences 707:719 the sequences encoding heavy and light chains of a monoclonal antibody (mAb) against protective antigen (PA) of Bacillius anthracis 707:837 Furthermore, we have engineered a miniBYV vector carrying the sequences encoding heavy and light chains of a monoclonal antibody (mAb) against protective antigen (PA) of Bacillius anthracis, and achieved the expression of the full-length functional anti-PA mAb at ~300 mg/kg of fresh leaf tissue. 25280556 5 34 theme miniBYV 683:689 arg1 vector 691:696 a miniBYV vector 681:696 a miniBYV vector carrying the sequences encoding heavy and light chains of a monoclonal antibody (mAb) against protective antigen (PA) of Bacillius anthracis 681:837 Furthermore, we have engineered a miniBYV vector carrying the sequences encoding heavy and light chains of a monoclonal antibody (mAb) against protective antigen (PA) of Bacillius anthracis, and achieved the expression of the full-length functional anti-PA mAb at ~300 mg/kg of fresh leaf tissue. 25280556 7 35 theme N-linked 1375:1382 arg1 glycosylation 1384:1396 N-linked glycosylation 1375:1396 N-linked glycosylation 1375:1396 Agroinfiltration of N. benthamiana with this miniBYV vector resulted in accumulation of biologically active Pfs48/45 that was devoid of N-linked glycosylation and had correct conformation and epitope display. 25280556 3 36 theme genes 450:454 arg1 co-delivery 424:434 co-delivery 424:434 co-delivery of two target genes into the same host cell 424:478 Here, we have developed a single-replicon vector based on beet yellows virus (BYV) that enables co-delivery of two target genes into the same host cell, resulting in transient expression of each target. 25280556 5 37 theme full-length 875:885 arg1 mAb 906:908 the full-length functional anti-PA mAb 871:908 the full-length functional anti-PA mAb 871:908 Furthermore, we have engineered a miniBYV vector carrying the sequences encoding heavy and light chains of a monoclonal antibody (mAb) against protective antigen (PA) of Bacillius anthracis, and achieved the expression of the full-length functional anti-PA mAb at ~300 mg/kg of fresh leaf tissue. 25280556 7 38 contain had 1402:1404 arg2 display 1439:1445 epitope display 1431:1445 epitope display 1431:1445 Agroinfiltration of N. benthamiana with this miniBYV vector resulted in accumulation of biologically active Pfs48/45 that was devoid of N-linked glycosylation and had correct conformation and epitope display. 25280556 7 38 contain had 1402:1404 arg2 conformation 1414:1425 correct conformation 1406:1425 correct conformation 1406:1425 Agroinfiltration of N. benthamiana with this miniBYV vector resulted in accumulation of biologically active Pfs48/45 that was devoid of N-linked glycosylation and had correct conformation and epitope display. 25280556 7 38 contain had 1402:1404 arg1 Pfs48/45 1347:1354 biologically active Pfs48/45 1327:1354 biologically active Pfs48/45 that was devoid of N-linked glycosylation and had correct conformation and epitope display 1327:1445 Agroinfiltration of N. benthamiana with this miniBYV vector resulted in accumulation of biologically active Pfs48/45 that was devoid of N-linked glycosylation and had correct conformation and epitope display. 25280556 7 39 theme correct 1406:1412 arg1 conformation 1414:1425 correct conformation 1406:1425 correct conformation 1406:1425 Agroinfiltration of N. benthamiana with this miniBYV vector resulted in accumulation of biologically active Pfs48/45 that was devoid of N-linked glycosylation and had correct conformation and epitope display. 25280556 6 40 theme F 1115:1115 arg1 protein 1062:1068 the Pfs48/45 protein 1049:1068 the Pfs48/45 protein of Plasmodium falciparum and endoglycosidase F (PNGase F) 1049:1126 To demonstrate co-expression and functionality of two independent proteins, we cloned the sequences of the Pfs48/45 protein of Plasmodium falciparum and endoglycosidase F (PNGase F) from Flavobacterium meningosepticum into the miniBYV vector under the control of two subgenomic RNA promoters. 25280556 8 41 theme recombinant 1564:1574 arg1 proteins 1576:1583 two functionally active recombinant proteins 1540:1583 two functionally active recombinant proteins within the same host cell 1540:1609 Overall, our findings demonstrate that the new BYV-based vector is capable of co-expressing two functionally active recombinant proteins within the same host cell. 25280556 4 42 theme host 614:617 arg1 plant 619:623 the host plant 610:623 the host plant 610:623 This BYV vector maintained genetic stability during systemic spread throughout the host plant, Nicotiana benthamiana. 25280556 0 43 theme vector 41:46 arg1 Development 0:10 Development 0:10 Development of a single-replicon miniBYV vector for co-expression of heterologous proteins. 0:90 Development of a single-replicon miniBYV vector for co-expression of heterologous proteins. 25280556 4 44 theme BYV 536:538 arg1 vector 540:545 This BYV vector 531:545 This BYV vector 531:545 This BYV vector maintained genetic stability during systemic spread throughout the host plant, Nicotiana benthamiana. 25280556 7 45 theme benthamiana 1262:1272 arg1 Agroinfiltration 1239:1254 Agroinfiltration 1239:1254 Agroinfiltration of N. benthamiana with this miniBYV vector 1239:1297 Agroinfiltration of N. benthamiana with this miniBYV vector resulted in accumulation of biologically active Pfs48/45 that was devoid of N-linked glycosylation and had correct conformation and epitope display. 25280556 2 46 theme target 251:256 arg1 proteins 258:265 target proteins 251:265 target proteins 251:265 With the broadening range of target proteins, the need for vectors with higher performance is increasing. 25280556 6 47 theme proteins 1012:1019 arg1 functionality 979:991 functionality 979:991 functionality 979:991 To demonstrate co-expression and functionality of two independent proteins, we cloned the sequences of the Pfs48/45 protein of Plasmodium falciparum and endoglycosidase F (PNGase F) from Flavobacterium meningosepticum into the miniBYV vector under the control of two subgenomic RNA promoters. 25280556 6 47 theme proteins 1012:1019 arg1 co-expression 961:973 co-expression 961:973 co-expression 961:973 To demonstrate co-expression and functionality of two independent proteins, we cloned the sequences of the Pfs48/45 protein of Plasmodium falciparum and endoglycosidase F (PNGase F) from Flavobacterium meningosepticum into the miniBYV vector under the control of two subgenomic RNA promoters. 25280556 0 48 theme miniBYV 33:39 arg1 vector 41:46 a single-replicon miniBYV vector 15:46 a single-replicon miniBYV vector for co-expression of heterologous proteins 15:89 Development of a single-replicon miniBYV vector for co-expression of heterologous proteins. 25280556 5 49 theme antibody 769:776 arg1 chains 746:751 heavy and light chains 730:751 heavy and light chains of a monoclonal antibody (mAb) against protective antigen (PA) of Bacillius anthracis 730:837 Furthermore, we have engineered a miniBYV vector carrying the sequences encoding heavy and light chains of a monoclonal antibody (mAb) against protective antigen (PA) of Bacillius anthracis, and achieved the expression of the full-length functional anti-PA mAb at ~300 mg/kg of fresh leaf tissue. 25280556 5 50 theme protective 792:801 arg1 PA 812:813 PA 812:813 PA 812:813 Furthermore, we have engineered a miniBYV vector carrying the sequences encoding heavy and light chains of a monoclonal antibody (mAb) against protective antigen (PA) of Bacillius anthracis, and achieved the expression of the full-length functional anti-PA mAb at ~300 mg/kg of fresh leaf tissue. 25280556 5 50 theme protective 792:801 arg1 antigen 803:809 protective antigen 792:809 protective antigen (PA) of Bacillius anthracis 792:837 Furthermore, we have engineered a miniBYV vector carrying the sequences encoding heavy and light chains of a monoclonal antibody (mAb) against protective antigen (PA) of Bacillius anthracis, and achieved the expression of the full-length functional anti-PA mAb at ~300 mg/kg of fresh leaf tissue. 25280556 3 51 theme target 443:448 arg1 genes 450:454 two target genes 439:454 two target genes 439:454 Here, we have developed a single-replicon vector based on beet yellows virus (BYV) that enables co-delivery of two target genes into the same host cell, resulting in transient expression of each target. 25280556 8 52 theme host 1601:1604 arg1 cell 1606:1609 the same host cell 1592:1609 the same host cell 1592:1609 Overall, our findings demonstrate that the new BYV-based vector is capable of co-expressing two functionally active recombinant proteins within the same host cell. 25280556 6 53 theme independent 1000:1010 arg1 proteins 1012:1019 two independent proteins 996:1019 two independent proteins 996:1019 To demonstrate co-expression and functionality of two independent proteins, we cloned the sequences of the Pfs48/45 protein of Plasmodium falciparum and endoglycosidase F (PNGase F) from Flavobacterium meningosepticum into the miniBYV vector under the control of two subgenomic RNA promoters. 25280556 6 54 theme falciparum 1084:1093 arg1 protein 1062:1068 the Pfs48/45 protein 1049:1068 the Pfs48/45 protein of Plasmodium falciparum and endoglycosidase F (PNGase F) 1049:1126 To demonstrate co-expression and functionality of two independent proteins, we cloned the sequences of the Pfs48/45 protein of Plasmodium falciparum and endoglycosidase F (PNGase F) from Flavobacterium meningosepticum into the miniBYV vector under the control of two subgenomic RNA promoters. 25280556 3 55 theme host 470:473 arg1 cell 475:478 the same host cell 461:478 the same host cell 461:478 Here, we have developed a single-replicon vector based on beet yellows virus (BYV) that enables co-delivery of two target genes into the same host cell, resulting in transient expression of each target. 25280556 8 56 theme BYV-based 1495:1503 arg1 capable 1515:1521 capable 1515:1521 capable 1515:1521 Overall, our findings demonstrate that the new BYV-based vector is capable of co-expressing two functionally active recombinant proteins within the same host cell. 25280556 8 56 theme BYV-based 1495:1503 arg1 vector 1505:1510 the new BYV-based vector 1487:1510 the new BYV-based vector 1487:1510 Overall, our findings demonstrate that the new BYV-based vector is capable of co-expressing two functionally active recombinant proteins within the same host cell. 25280556 8 57 theme same 1596:1599 arg1 cell 1606:1609 the same host cell 1592:1609 the same host cell 1592:1609 Overall, our findings demonstrate that the new BYV-based vector is capable of co-expressing two functionally active recombinant proteins within the same host cell. 25280556 2 58 theme broadening 231:240 arg1 range 242:246 the broadening range 227:246 the broadening range of target proteins 227:265 With the broadening range of target proteins, the need for vectors with higher performance is increasing. 25280556 1 59 theme proteins 128:135 arg1 production 102:111 production 102:111 production of recombinant proteins, including vaccine antigens and monoclonal antibodies, 102:190 In planta production of recombinant proteins, including vaccine antigens and monoclonal antibodies, continues gaining acceptance. 25280556 7 60 theme active 1340:1345 arg1 Pfs48/45 1347:1354 biologically active Pfs48/45 1327:1354 biologically active Pfs48/45 that was devoid of N-linked glycosylation and had correct conformation and epitope display 1327:1445 Agroinfiltration of N. benthamiana with this miniBYV vector resulted in accumulation of biologically active Pfs48/45 that was devoid of N-linked glycosylation and had correct conformation and epitope display. 25280556 5 61 theme functional 887:896 arg1 mAb 906:908 the full-length functional anti-PA mAb 871:908 the full-length functional anti-PA mAb 871:908 Furthermore, we have engineered a miniBYV vector carrying the sequences encoding heavy and light chains of a monoclonal antibody (mAb) against protective antigen (PA) of Bacillius anthracis, and achieved the expression of the full-length functional anti-PA mAb at ~300 mg/kg of fresh leaf tissue. 25280556 6 62 theme Plasmodium 1073:1082 arg1 falciparum 1084:1093 Plasmodium falciparum 1073:1093 Plasmodium falciparum 1073:1093 To demonstrate co-expression and functionality of two independent proteins, we cloned the sequences of the Pfs48/45 protein of Plasmodium falciparum and endoglycosidase F (PNGase F) from Flavobacterium meningosepticum into the miniBYV vector under the control of two subgenomic RNA promoters. 25280556 2 63 with vectors 281:287 arg1 performance 301:311 higher performance 294:311 higher performance 294:311 With the broadening range of target proteins, the need for vectors with higher performance is increasing. 25280556 7 64 theme N. 1259:1260 arg1 benthamiana 1262:1272 N. benthamiana 1259:1272 N. benthamiana 1259:1272 Agroinfiltration of N. benthamiana with this miniBYV vector resulted in accumulation of biologically active Pfs48/45 that was devoid of N-linked glycosylation and had correct conformation and epitope display. 25280556 6 65 theme miniBYV 1173:1179 arg1 vector 1181:1186 the miniBYV vector 1169:1186 the miniBYV vector 1169:1186 To demonstrate co-expression and functionality of two independent proteins, we cloned the sequences of the Pfs48/45 protein of Plasmodium falciparum and endoglycosidase F (PNGase F) from Flavobacterium meningosepticum into the miniBYV vector under the control of two subgenomic RNA promoters. 25280556 3 66 theme same 465:468 arg1 cell 475:478 the same host cell 461:478 the same host cell 461:478 Here, we have developed a single-replicon vector based on beet yellows virus (BYV) that enables co-delivery of two target genes into the same host cell, resulting in transient expression of each target. 25280556 6 67 theme endoglycosidase 1099:1113 arg1 F 1115:1115 endoglycosidase F 1099:1115 endoglycosidase F (PNGase F) 1099:1126 To demonstrate co-expression and functionality of two independent proteins, we cloned the sequences of the Pfs48/45 protein of Plasmodium falciparum and endoglycosidase F (PNGase F) from Flavobacterium meningosepticum into the miniBYV vector under the control of two subgenomic RNA promoters. 25280556 6 67 theme endoglycosidase 1099:1113 arg1 F 1125:1125 PNGase F 1118:1125 PNGase F 1118:1125 To demonstrate co-expression and functionality of two independent proteins, we cloned the sequences of the Pfs48/45 protein of Plasmodium falciparum and endoglycosidase F (PNGase F) from Flavobacterium meningosepticum into the miniBYV vector under the control of two subgenomic RNA promoters. 25280556 4 68 theme systemic 583:590 arg1 spread 592:597 systemic spread 583:597 systemic spread throughout the host plant 583:623 This BYV vector maintained genetic stability during systemic spread throughout the host plant, Nicotiana benthamiana. 25280556 0 69 theme heterologous 69:80 arg1 proteins 82:89 heterologous proteins 69:89 heterologous proteins 69:89 Development of a single-replicon miniBYV vector for co-expression of heterologous proteins. 25280556 6 70 theme protein 1062:1068 arg1 sequences 1036:1044 the sequences 1032:1044 the sequences of the Pfs48/45 protein of Plasmodium falciparum and endoglycosidase F (PNGase F) from Flavobacterium meningosepticum 1032:1162 To demonstrate co-expression and functionality of two independent proteins, we cloned the sequences of the Pfs48/45 protein of Plasmodium falciparum and endoglycosidase F (PNGase F) from Flavobacterium meningosepticum into the miniBYV vector under the control of two subgenomic RNA promoters. 25280556 7 71 with Agroinfiltration 1239:1254 arg1 vector 1292:1297 this miniBYV vector 1279:1297 this miniBYV vector 1279:1297 Agroinfiltration of N. benthamiana with this miniBYV vector resulted in accumulation of biologically active Pfs48/45 that was devoid of N-linked glycosylation and had correct conformation and epitope display. 25280556 1 72 theme vaccine 148:154 arg1 antigens 156:163 vaccine antigens 148:163 vaccine antigens 148:163 In planta production of recombinant proteins, including vaccine antigens and monoclonal antibodies, continues gaining acceptance. 25280556 8 73 theme new 1491:1493 arg1 capable 1515:1521 capable 1515:1521 capable 1515:1521 Overall, our findings demonstrate that the new BYV-based vector is capable of co-expressing two functionally active recombinant proteins within the same host cell. 25280556 8 73 theme new 1491:1493 arg1 vector 1505:1510 the new BYV-based vector 1487:1510 the new BYV-based vector 1487:1510 Overall, our findings demonstrate that the new BYV-based vector is capable of co-expressing two functionally active recombinant proteins within the same host cell. 25280556 2 74 theme proteins 258:265 arg1 range 242:246 the broadening range 227:246 the broadening range of target proteins 227:265 With the broadening range of target proteins, the need for vectors with higher performance is increasing. 25280556 3 75 theme transient 494:502 arg1 expression 504:513 transient expression 494:513 transient expression of each target 494:528 Here, we have developed a single-replicon vector based on beet yellows virus (BYV) that enables co-delivery of two target genes into the same host cell, resulting in transient expression of each target. 25280556 7 76 theme glycosylation 1384:1396 arg1 devoid 1365:1370 devoid 1365:1370 devoid 1365:1370 Agroinfiltration of N. benthamiana with this miniBYV vector resulted in accumulation of biologically active Pfs48/45 that was devoid of N-linked glycosylation and had correct conformation and epitope display. 25245409 0 0 theme antimicrobial 79:91 arg1 protection 93:102 antimicrobial protection 79:102 antimicrobial protection 79:102 Monotreme lactation protein is highly expressed in monotreme milk and provides antimicrobial protection. 25245409 2 1 theme incubation 343:352 arg1 period 354:359 an even briefer incubation period 327:359 an even briefer incubation period 327:359 Monotremes lay eggs following a short gestation period and after an even briefer incubation period, altricial hatchlings are nourished over a long lactation period with milk secreted by nipple-less mammary patches located on the female's abdomen. 25245409 2 2 theme located 476:482 arg1 patches 468:474 nipple-less mammary patches 448:474 nipple-less mammary patches located on the female's abdomen 448:506 Monotremes lay eggs following a short gestation period and after an even briefer incubation period, altricial hatchlings are nourished over a long lactation period with milk secreted by nipple-less mammary patches located on the female's abdomen. 25245409 2 3 theme briefer 335:341 arg1 period 354:359 an even briefer incubation period 327:359 an even briefer incubation period 327:359 Monotremes lay eggs following a short gestation period and after an even briefer incubation period, altricial hatchlings are nourished over a long lactation period with milk secreted by nipple-less mammary patches located on the female's abdomen. 25245409 8 4 from effect 1481:1486 arg1 enterica 1576:1583 Salmonella enterica 1565:1583 Salmonella enterica 1565:1583 Functional analysis revealed MLP antibacterial activity against both opportunistic pathogenic Staphylococcus aureus and commensal Enterococcus faecalis bacteria but showed no effect on Escherichia coli, Pseudomonas aeruginosa, Staphylococcus epidermidis, and Salmonella enterica. 25245409 8 4 from effect 1481:1486 arg1 coli 1503:1506 Escherichia coli 1491:1506 Escherichia coli 1491:1506 Functional analysis revealed MLP antibacterial activity against both opportunistic pathogenic Staphylococcus aureus and commensal Enterococcus faecalis bacteria but showed no effect on Escherichia coli, Pseudomonas aeruginosa, Staphylococcus epidermidis, and Salmonella enterica. 25245409 8 4 from effect 1481:1486 arg1 aeruginosa 1521:1530 Pseudomonas aeruginosa 1509:1530 Pseudomonas aeruginosa 1509:1530 Functional analysis revealed MLP antibacterial activity against both opportunistic pathogenic Staphylococcus aureus and commensal Enterococcus faecalis bacteria but showed no effect on Escherichia coli, Pseudomonas aeruginosa, Staphylococcus epidermidis, and Salmonella enterica. 25245409 8 4 from effect 1481:1486 arg1 epidermidis 1548:1558 Staphylococcus epidermidis 1533:1558 Staphylococcus epidermidis 1533:1558 Functional analysis revealed MLP antibacterial activity against both opportunistic pathogenic Staphylococcus aureus and commensal Enterococcus faecalis bacteria but showed no effect on Escherichia coli, Pseudomonas aeruginosa, Staphylococcus epidermidis, and Salmonella enterica. 25245409 7 5 theme typical 1263:1269 arg1 protein 1252:1258 an amphipathic, α-helical protein 1226:1258 protein 1252:1258 Analysis of recombinant MLP showed that it is an N-linked glycosylated protein and biophysical studies predicted that MLP is an amphipathic, α-helical protein, a typical feature of antimicrobial proteins. 25245409 7 5 theme typical 1263:1269 arg1 feature 1271:1277 a typical feature 1261:1277 a typical feature of antimicrobial proteins 1261:1303 Analysis of recombinant MLP showed that it is an N-linked glycosylated protein and biophysical studies predicted that MLP is an amphipathic, α-helical protein, a typical feature of antimicrobial proteins. 25245409 9 6 theme milk-mediated 1654:1666 arg1 immunity 1675:1682 milk-mediated innate immunity 1654:1682 milk-mediated innate immunity 1654:1682 Our data suggest that MLP is an evolutionarily ancient component of milk-mediated innate immunity absent in other mammals. 25245409 7 7 theme α-helical 1242:1250 arg1 MLP 1219:1221 MLP 1219:1221 MLP 1219:1221 Analysis of recombinant MLP showed that it is an N-linked glycosylated protein and biophysical studies predicted that MLP is an amphipathic, α-helical protein, a typical feature of antimicrobial proteins. 25245409 7 7 theme α-helical 1242:1250 arg1 protein 1252:1258 an amphipathic, α-helical protein 1226:1258 protein 1252:1258 Analysis of recombinant MLP showed that it is an N-linked glycosylated protein and biophysical studies predicted that MLP is an amphipathic, α-helical protein, a typical feature of antimicrobial proteins. 25245409 7 7 theme α-helical 1242:1250 arg1 feature 1271:1277 a typical feature 1261:1277 a typical feature of antimicrobial proteins 1261:1303 Analysis of recombinant MLP showed that it is an N-linked glycosylated protein and biophysical studies predicted that MLP is an amphipathic, α-helical protein, a typical feature of antimicrobial proteins. 25245409 3 8 theme sole 521:524 arg1 source 526:531 the sole source 517:531 the sole source of nutrition and immune protection for the developing young until weaning 517:605 Milk is the sole source of nutrition and immune protection for the developing young until weaning. 25245409 3 8 theme sole 521:524 arg1 Milk 509:512 Milk 509:512 Milk 509:512 Milk is the sole source of nutrition and immune protection for the developing young until weaning. 25245409 4 9 theme Lactation 724:732 arg1 MLP 743:745 MLP 743:745 MLP 743:745 Using transcriptome and mass spectrometry analysis of milk cells and milk proteins, respectively, a novel Monotreme Lactation Protein (MLP) was identified as a major secreted protein in milk. 25245409 4 9 theme Lactation 724:732 arg1 Protein 734:740 a novel Monotreme Lactation Protein 706:740 a novel Monotreme Lactation Protein (MLP) 706:746 Using transcriptome and mass spectrometry analysis of milk cells and milk proteins, respectively, a novel Monotreme Lactation Protein (MLP) was identified as a major secreted protein in milk. 25245409 4 9 theme Lactation 724:732 arg1 protein 783:789 a major secreted protein 766:789 a major secreted protein in milk 766:797 Using transcriptome and mass spectrometry analysis of milk cells and milk proteins, respectively, a novel Monotreme Lactation Protein (MLP) was identified as a major secreted protein in milk. 25245409 1 10 theme reproduction 248:259 arg1 mode 240:243 mode 240:243 mode of reproduction 240:259 Monotremes (platypus and echidna) are the descendants of the oldest ancestor of all extant mammals distinguished from other mammals by mode of reproduction. 25245409 6 11 located observed 1015:1022 arg1 cells 1032:1036 milk cells 1027:1036 milk cells 1027:1036 The MLP transcript was shown to be expressed in a variety of tissues; however, highest expression was observed in milk cells and was expressed constitutively from early to late lactation. 25245409 6 11 located observed 1015:1022 arg2 expression 1000:1009 highest expression 992:1009 highest expression 992:1009 The MLP transcript was shown to be expressed in a variety of tissues; however, highest expression was observed in milk cells and was expressed constitutively from early to late lactation. 25245409 9 12 theme innate 1668:1673 arg1 immunity 1675:1682 milk-mediated innate immunity 1654:1682 milk-mediated innate immunity 1654:1682 Our data suggest that MLP is an evolutionarily ancient component of milk-mediated innate immunity absent in other mammals. 25245409 7 13 theme biophysical 1184:1194 arg1 studies 1196:1202 biophysical studies 1184:1202 biophysical studies 1184:1202 Analysis of recombinant MLP showed that it is an N-linked glycosylated protein and biophysical studies predicted that MLP is an amphipathic, α-helical protein, a typical feature of antimicrobial proteins. 25245409 4 14 theme proteins 682:689 arg1 analysis 650:657 transcriptome and mass spectrometry analysis 614:657 analysis 650:657 Using transcriptome and mass spectrometry analysis of milk cells and milk proteins, respectively, a novel Monotreme Lactation Protein (MLP) was identified as a major secreted protein in milk. 25245409 4 15 theme milk 677:680 arg1 proteins 682:689 milk proteins 677:689 milk proteins 677:689 Using transcriptome and mass spectrometry analysis of milk cells and milk proteins, respectively, a novel Monotreme Lactation Protein (MLP) was identified as a major secreted protein in milk. 25245409 9 16 theme immunity 1675:1682 arg1 component 1641:1649 an evolutionarily ancient component 1615:1649 an evolutionarily ancient component of milk-mediated innate immunity absent in other mammals 1615:1706 Our data suggest that MLP is an evolutionarily ancient component of milk-mediated innate immunity absent in other mammals. 25245409 9 16 theme immunity 1675:1682 arg1 MLP 1608:1610 MLP 1608:1610 MLP 1608:1610 Our data suggest that MLP is an evolutionarily ancient component of milk-mediated innate immunity absent in other mammals. 25245409 2 17 theme long 404:407 arg1 period 419:424 a long lactation period 402:424 a long lactation period with milk secreted by nipple-less mammary patches located on the female's abdomen 402:506 Monotremes lay eggs following a short gestation period and after an even briefer incubation period, altricial hatchlings are nourished over a long lactation period with milk secreted by nipple-less mammary patches located on the female's abdomen. 25245409 4 18 theme milk 662:665 arg1 cells 667:671 milk cells 662:671 milk cells 662:671 Using transcriptome and mass spectrometry analysis of milk cells and milk proteins, respectively, a novel Monotreme Lactation Protein (MLP) was identified as a major secreted protein in milk. 25245409 5 19 theme platypus 813:820 arg1 genes 851:855 platypus and short-beaked echidna MLP genes 813:855 platypus and short-beaked echidna MLP genes 813:855 We show that platypus and short-beaked echidna MLP genes show significant homology and are unique to monotremes. 25245409 5 20 theme significant 862:872 arg1 homology 874:881 significant homology 862:881 significant homology 862:881 We show that platypus and short-beaked echidna MLP genes show significant homology and are unique to monotremes. 25245409 7 21 gly glycosylated 1159:1170 arg1 it 1141:1142 it 1141:1142 it 1141:1142 Analysis of recombinant MLP showed that it is an N-linked glycosylated protein and biophysical studies predicted that MLP is an amphipathic, α-helical protein, a typical feature of antimicrobial proteins. 25245409 7 21 gly glycosylated 1159:1170 arg1 protein 1172:1178 an N-linked glycosylated protein 1147:1178 an N-linked glycosylated protein 1147:1178 Analysis of recombinant MLP showed that it is an N-linked glycosylated protein and biophysical studies predicted that MLP is an amphipathic, α-helical protein, a typical feature of antimicrobial proteins. 25245409 7 22 theme MLP 1125:1127 arg1 Analysis 1101:1108 Analysis 1101:1108 Analysis of recombinant MLP 1101:1127 Analysis of recombinant MLP showed that it is an N-linked glycosylated protein and biophysical studies predicted that MLP is an amphipathic, α-helical protein, a typical feature of antimicrobial proteins. 25245409 6 23 theme milk 1027:1030 arg1 cells 1032:1036 milk cells 1027:1036 milk cells 1027:1036 The MLP transcript was shown to be expressed in a variety of tissues; however, highest expression was observed in milk cells and was expressed constitutively from early to late lactation. 25245409 1 24 theme oldest 166:171 arg1 ancestor 173:180 the oldest ancestor 162:180 the oldest ancestor of all extant mammals distinguished from other mammals by mode of reproduction 162:259 Monotremes (platypus and echidna) are the descendants of the oldest ancestor of all extant mammals distinguished from other mammals by mode of reproduction. 25245409 0 25 theme lactation 10:18 arg1 protein 20:26 Monotreme lactation protein 0:26 Monotreme lactation protein 0:26 Monotreme lactation protein is highly expressed in monotreme milk and provides antimicrobial protection. 25245409 7 26 theme N-linked 1150:1157 arg1 it 1141:1142 it 1141:1142 it 1141:1142 Analysis of recombinant MLP showed that it is an N-linked glycosylated protein and biophysical studies predicted that MLP is an amphipathic, α-helical protein, a typical feature of antimicrobial proteins. 25245409 7 26 theme N-linked 1150:1157 arg1 protein 1172:1178 an N-linked glycosylated protein 1147:1178 an N-linked glycosylated protein 1147:1178 Analysis of recombinant MLP showed that it is an N-linked glycosylated protein and biophysical studies predicted that MLP is an amphipathic, α-helical protein, a typical feature of antimicrobial proteins. 25245409 7 27 theme amphipathic 1229:1239 arg1 MLP 1219:1221 MLP 1219:1221 MLP 1219:1221 Analysis of recombinant MLP showed that it is an N-linked glycosylated protein and biophysical studies predicted that MLP is an amphipathic, α-helical protein, a typical feature of antimicrobial proteins. 25245409 7 27 theme amphipathic 1229:1239 arg1 protein 1252:1258 an amphipathic, α-helical protein 1226:1258 protein 1252:1258 Analysis of recombinant MLP showed that it is an N-linked glycosylated protein and biophysical studies predicted that MLP is an amphipathic, α-helical protein, a typical feature of antimicrobial proteins. 25245409 7 27 theme amphipathic 1229:1239 arg1 feature 1271:1277 a typical feature 1261:1277 a typical feature of antimicrobial proteins 1261:1303 Analysis of recombinant MLP showed that it is an N-linked glycosylated protein and biophysical studies predicted that MLP is an amphipathic, α-helical protein, a typical feature of antimicrobial proteins. 25245409 10 28 theme bacterial 1841:1849 arg1 protection 1851:1860 bacterial protection 1841:1860 bacterial protection 1841:1860 We propose that MLP evolved specifically in the monotreme lineage supporting the evolution of lactation in these species to provide bacterial protection, at a time when mammals lacked nipples. 25245409 4 29 theme Monotreme 714:722 arg1 MLP 743:745 MLP 743:745 MLP 743:745 Using transcriptome and mass spectrometry analysis of milk cells and milk proteins, respectively, a novel Monotreme Lactation Protein (MLP) was identified as a major secreted protein in milk. 25245409 4 29 theme Monotreme 714:722 arg1 Protein 734:740 a novel Monotreme Lactation Protein 706:740 a novel Monotreme Lactation Protein (MLP) 706:746 Using transcriptome and mass spectrometry analysis of milk cells and milk proteins, respectively, a novel Monotreme Lactation Protein (MLP) was identified as a major secreted protein in milk. 25245409 4 29 theme Monotreme 714:722 arg1 protein 783:789 a major secreted protein 766:789 a major secreted protein in milk 766:797 Using transcriptome and mass spectrometry analysis of milk cells and milk proteins, respectively, a novel Monotreme Lactation Protein (MLP) was identified as a major secreted protein in milk. 25245409 7 30 theme recombinant 1113:1123 arg1 MLP 1125:1127 recombinant MLP 1113:1127 recombinant MLP 1113:1127 Analysis of recombinant MLP showed that it is an N-linked glycosylated protein and biophysical studies predicted that MLP is an amphipathic, α-helical protein, a typical feature of antimicrobial proteins. 25245409 1 31 theme ancestor 173:180 arg1 Monotremes 105:114 Monotremes 105:114 Monotremes (platypus and echidna) 105:137 Monotremes (platypus and echidna) are the descendants of the oldest ancestor of all extant mammals distinguished from other mammals by mode of reproduction. 25245409 1 31 theme ancestor 173:180 arg1 descendants 147:157 the descendants 143:157 the descendants of the oldest ancestor of all extant mammals distinguished from other mammals by mode of reproduction 143:259 Monotremes (platypus and echidna) are the descendants of the oldest ancestor of all extant mammals distinguished from other mammals by mode of reproduction. 25245409 0 32 theme Monotreme 0:8 arg1 protein 20:26 Monotreme lactation protein 0:26 Monotreme lactation protein 0:26 Monotreme lactation protein is highly expressed in monotreme milk and provides antimicrobial protection. 25245409 9 33 theme other 1694:1698 arg1 mammals 1700:1706 other mammals 1694:1706 other mammals 1694:1706 Our data suggest that MLP is an evolutionarily ancient component of milk-mediated innate immunity absent in other mammals. 25245409 2 34 theme gestation 300:308 arg1 period 310:315 a short gestation period 292:315 a short gestation period 292:315 Monotremes lay eggs following a short gestation period and after an even briefer incubation period, altricial hatchlings are nourished over a long lactation period with milk secreted by nipple-less mammary patches located on the female's abdomen. 25245409 8 35 theme opportunistic 1375:1387 arg1 bacteria 1458:1465 both opportunistic pathogenic Staphylococcus aureus and commensal Enterococcus faecalis bacteria 1370:1465 both opportunistic pathogenic Staphylococcus aureus and commensal Enterococcus faecalis bacteria 1370:1465 Functional analysis revealed MLP antibacterial activity against both opportunistic pathogenic Staphylococcus aureus and commensal Enterococcus faecalis bacteria but showed no effect on Escherichia coli, Pseudomonas aeruginosa, Staphylococcus epidermidis, and Salmonella enterica. 25245409 2 36 theme altricial 362:370 arg1 hatchlings 372:381 altricial hatchlings 362:381 altricial hatchlings 362:381 Monotremes lay eggs following a short gestation period and after an even briefer incubation period, altricial hatchlings are nourished over a long lactation period with milk secreted by nipple-less mammary patches located on the female's abdomen. 25245409 8 37 dep Enterococcus 1436:1447 arg1 faecalis 1449:1456 faecalis 1449:1456 faecalis 1449:1456 Functional analysis revealed MLP antibacterial activity against both opportunistic pathogenic Staphylococcus aureus and commensal Enterococcus faecalis bacteria but showed no effect on Escherichia coli, Pseudomonas aeruginosa, Staphylococcus epidermidis, and Salmonella enterica. 25245409 4 38 theme novel 708:712 arg1 MLP 743:745 MLP 743:745 MLP 743:745 Using transcriptome and mass spectrometry analysis of milk cells and milk proteins, respectively, a novel Monotreme Lactation Protein (MLP) was identified as a major secreted protein in milk. 25245409 4 38 theme novel 708:712 arg1 Protein 734:740 a novel Monotreme Lactation Protein 706:740 a novel Monotreme Lactation Protein (MLP) 706:746 Using transcriptome and mass spectrometry analysis of milk cells and milk proteins, respectively, a novel Monotreme Lactation Protein (MLP) was identified as a major secreted protein in milk. 25245409 4 38 theme novel 708:712 arg1 protein 783:789 a major secreted protein 766:789 a major secreted protein in milk 766:797 Using transcriptome and mass spectrometry analysis of milk cells and milk proteins, respectively, a novel Monotreme Lactation Protein (MLP) was identified as a major secreted protein in milk. 25245409 10 39 theme lactation 1803:1811 arg1 evolution 1790:1798 the evolution 1786:1798 the evolution of lactation in these species 1786:1828 We propose that MLP evolved specifically in the monotreme lineage supporting the evolution of lactation in these species to provide bacterial protection, at a time when mammals lacked nipples. 25245409 2 40 theme short 294:298 arg1 period 310:315 a short gestation period 292:315 a short gestation period 292:315 Monotremes lay eggs following a short gestation period and after an even briefer incubation period, altricial hatchlings are nourished over a long lactation period with milk secreted by nipple-less mammary patches located on the female's abdomen. 25245409 2 41 theme lactation 409:417 arg1 period 419:424 a long lactation period 402:424 a long lactation period with milk secreted by nipple-less mammary patches located on the female's abdomen 402:506 Monotremes lay eggs following a short gestation period and after an even briefer incubation period, altricial hatchlings are nourished over a long lactation period with milk secreted by nipple-less mammary patches located on the female's abdomen. 25245409 3 42 theme immune 550:555 arg1 protection 557:566 immune protection 550:566 immune protection 550:566 Milk is the sole source of nutrition and immune protection for the developing young until weaning. 25245409 8 43 theme commensal 1426:1434 arg1 bacteria 1458:1465 both opportunistic pathogenic Staphylococcus aureus and commensal Enterococcus faecalis bacteria 1370:1465 both opportunistic pathogenic Staphylococcus aureus and commensal Enterococcus faecalis bacteria 1370:1465 Functional analysis revealed MLP antibacterial activity against both opportunistic pathogenic Staphylococcus aureus and commensal Enterococcus faecalis bacteria but showed no effect on Escherichia coli, Pseudomonas aeruginosa, Staphylococcus epidermidis, and Salmonella enterica. 25245409 3 44 theme nutrition 536:544 arg1 source 526:531 the sole source 517:531 the sole source of nutrition and immune protection for the developing young until weaning 517:605 Milk is the sole source of nutrition and immune protection for the developing young until weaning. 25245409 3 44 theme nutrition 536:544 arg1 Milk 509:512 Milk 509:512 Milk 509:512 Milk is the sole source of nutrition and immune protection for the developing young until weaning. 25245409 10 45 theme monotreme 1757:1765 arg1 lineage 1767:1773 the monotreme lineage 1753:1773 the monotreme lineage supporting the evolution of lactation in these species to provide bacterial protection 1753:1860 We propose that MLP evolved specifically in the monotreme lineage supporting the evolution of lactation in these species to provide bacterial protection, at a time when mammals lacked nipples. 25245409 1 46 theme extant 189:194 arg1 mammals 196:202 all extant mammals 185:202 all extant mammals distinguished from other mammals by mode of reproduction 185:259 Monotremes (platypus and echidna) are the descendants of the oldest ancestor of all extant mammals distinguished from other mammals by mode of reproduction. 25245409 6 47 theme MLP 917:919 arg1 transcript 921:930 The MLP transcript 913:930 The MLP transcript 913:930 The MLP transcript was shown to be expressed in a variety of tissues; however, highest expression was observed in milk cells and was expressed constitutively from early to late lactation. 25245409 4 48 theme mass 632:635 arg1 analysis 650:657 transcriptome and mass spectrometry analysis 614:657 analysis 650:657 Using transcriptome and mass spectrometry analysis of milk cells and milk proteins, respectively, a novel Monotreme Lactation Protein (MLP) was identified as a major secreted protein in milk. 25245409 5 49 theme echidna 839:845 arg1 genes 851:855 platypus and short-beaked echidna MLP genes 813:855 platypus and short-beaked echidna MLP genes 813:855 We show that platypus and short-beaked echidna MLP genes show significant homology and are unique to monotremes. 25245409 1 50 theme mammals 196:202 arg1 ancestor 173:180 the oldest ancestor 162:180 the oldest ancestor of all extant mammals distinguished from other mammals by mode of reproduction 162:259 Monotremes (platypus and echidna) are the descendants of the oldest ancestor of all extant mammals distinguished from other mammals by mode of reproduction. 25245409 2 51 theme mammary 460:466 arg1 patches 468:474 nipple-less mammary patches 448:474 nipple-less mammary patches located on the female's abdomen 448:506 Monotremes lay eggs following a short gestation period and after an even briefer incubation period, altricial hatchlings are nourished over a long lactation period with milk secreted by nipple-less mammary patches located on the female's abdomen. 25245409 5 52 theme short-beaked 826:837 arg1 genes 851:855 platypus and short-beaked echidna MLP genes 813:855 platypus and short-beaked echidna MLP genes 813:855 We show that platypus and short-beaked echidna MLP genes show significant homology and are unique to monotremes. 25245409 4 53 theme secreted 774:781 arg1 protein 783:789 a major secreted protein 766:789 a major secreted protein in milk 766:797 Using transcriptome and mass spectrometry analysis of milk cells and milk proteins, respectively, a novel Monotreme Lactation Protein (MLP) was identified as a major secreted protein in milk. 25245409 4 53 theme secreted 774:781 arg1 Protein 734:740 a novel Monotreme Lactation Protein 706:740 a novel Monotreme Lactation Protein (MLP) 706:746 Using transcriptome and mass spectrometry analysis of milk cells and milk proteins, respectively, a novel Monotreme Lactation Protein (MLP) was identified as a major secreted protein in milk. 25245409 2 54 theme nipple-less 448:458 arg1 patches 468:474 nipple-less mammary patches 448:474 nipple-less mammary patches located on the female's abdomen 448:506 Monotremes lay eggs following a short gestation period and after an even briefer incubation period, altricial hatchlings are nourished over a long lactation period with milk secreted by nipple-less mammary patches located on the female's abdomen. 25245409 5 55 theme MLP 847:849 arg1 genes 851:855 platypus and short-beaked echidna MLP genes 813:855 platypus and short-beaked echidna MLP genes 813:855 We show that platypus and short-beaked echidna MLP genes show significant homology and are unique to monotremes. 25245409 3 56 theme protection 557:566 arg1 source 526:531 the sole source 517:531 the sole source of nutrition and immune protection for the developing young until weaning 517:605 Milk is the sole source of nutrition and immune protection for the developing young until weaning. 25245409 3 56 theme protection 557:566 arg1 Milk 509:512 Milk 509:512 Milk 509:512 Milk is the sole source of nutrition and immune protection for the developing young until weaning. 25245409 2 57 with period 419:424 arg1 milk 431:434 milk 431:434 milk secreted by nipple-less mammary patches located on the female's abdomen 431:506 Monotremes lay eggs following a short gestation period and after an even briefer incubation period, altricial hatchlings are nourished over a long lactation period with milk secreted by nipple-less mammary patches located on the female's abdomen. 25245409 9 58 from absent 1684:1689 arg1 mammals 1700:1706 other mammals 1694:1706 other mammals 1694:1706 Our data suggest that MLP is an evolutionarily ancient component of milk-mediated innate immunity absent in other mammals. 25245409 9 59 theme absent 1684:1689 arg1 component 1641:1649 an evolutionarily ancient component 1615:1649 an evolutionarily ancient component of milk-mediated innate immunity absent in other mammals 1615:1706 Our data suggest that MLP is an evolutionarily ancient component of milk-mediated innate immunity absent in other mammals. 25245409 9 59 theme absent 1684:1689 arg1 MLP 1608:1610 MLP 1608:1610 MLP 1608:1610 Our data suggest that MLP is an evolutionarily ancient component of milk-mediated innate immunity absent in other mammals. 25245409 4 60 from protein 783:789 arg1 milk 794:797 milk 794:797 milk 794:797 Using transcriptome and mass spectrometry analysis of milk cells and milk proteins, respectively, a novel Monotreme Lactation Protein (MLP) was identified as a major secreted protein in milk. 25245409 8 61 dep Staphylococcus 1400:1413 arg1 aureus 1415:1420 aureus 1415:1420 aureus 1415:1420 Functional analysis revealed MLP antibacterial activity against both opportunistic pathogenic Staphylococcus aureus and commensal Enterococcus faecalis bacteria but showed no effect on Escherichia coli, Pseudomonas aeruginosa, Staphylococcus epidermidis, and Salmonella enterica. 25245409 9 62 theme ancient 1633:1639 arg1 component 1641:1649 an evolutionarily ancient component 1615:1649 an evolutionarily ancient component of milk-mediated innate immunity absent in other mammals 1615:1706 Our data suggest that MLP is an evolutionarily ancient component of milk-mediated innate immunity absent in other mammals. 25245409 9 62 theme ancient 1633:1639 arg1 MLP 1608:1610 MLP 1608:1610 MLP 1608:1610 Our data suggest that MLP is an evolutionarily ancient component of milk-mediated innate immunity absent in other mammals. 25245409 10 63 from evolution 1790:1798 arg1 species 1822:1828 these species 1816:1828 these species 1816:1828 We propose that MLP evolved specifically in the monotreme lineage supporting the evolution of lactation in these species to provide bacterial protection, at a time when mammals lacked nipples. 25245409 8 64 theme pathogenic 1389:1398 arg1 bacteria 1458:1465 both opportunistic pathogenic Staphylococcus aureus and commensal Enterococcus faecalis bacteria 1370:1465 both opportunistic pathogenic Staphylococcus aureus and commensal Enterococcus faecalis bacteria 1370:1465 Functional analysis revealed MLP antibacterial activity against both opportunistic pathogenic Staphylococcus aureus and commensal Enterococcus faecalis bacteria but showed no effect on Escherichia coli, Pseudomonas aeruginosa, Staphylococcus epidermidis, and Salmonella enterica. 25245409 7 65 theme proteins 1296:1303 arg1 protein 1252:1258 an amphipathic, α-helical protein 1226:1258 protein 1252:1258 Analysis of recombinant MLP showed that it is an N-linked glycosylated protein and biophysical studies predicted that MLP is an amphipathic, α-helical protein, a typical feature of antimicrobial proteins. 25245409 7 65 theme proteins 1296:1303 arg1 feature 1271:1277 a typical feature 1261:1277 a typical feature of antimicrobial proteins 1261:1303 Analysis of recombinant MLP showed that it is an N-linked glycosylated protein and biophysical studies predicted that MLP is an amphipathic, α-helical protein, a typical feature of antimicrobial proteins. 25245409 8 66 theme antibacterial 1339:1351 arg1 activity 1353:1360 MLP antibacterial activity 1335:1360 MLP antibacterial activity against both opportunistic pathogenic Staphylococcus aureus and commensal Enterococcus faecalis bacteria 1335:1465 Functional analysis revealed MLP antibacterial activity against both opportunistic pathogenic Staphylococcus aureus and commensal Enterococcus faecalis bacteria but showed no effect on Escherichia coli, Pseudomonas aeruginosa, Staphylococcus epidermidis, and Salmonella enterica. 25245409 8 67 dep pathogenic 1389:1398 arg1 Enterococcus 1436:1447 Enterococcus 1436:1447 Enterococcus 1436:1447 Functional analysis revealed MLP antibacterial activity against both opportunistic pathogenic Staphylococcus aureus and commensal Enterococcus faecalis bacteria but showed no effect on Escherichia coli, Pseudomonas aeruginosa, Staphylococcus epidermidis, and Salmonella enterica. 25245409 8 67 dep pathogenic 1389:1398 arg1 Staphylococcus 1400:1413 Staphylococcus 1400:1413 Staphylococcus 1400:1413 Functional analysis revealed MLP antibacterial activity against both opportunistic pathogenic Staphylococcus aureus and commensal Enterococcus faecalis bacteria but showed no effect on Escherichia coli, Pseudomonas aeruginosa, Staphylococcus epidermidis, and Salmonella enterica. 25245409 6 68 theme late 1085:1088 arg1 lactation 1090:1098 late lactation 1085:1098 late lactation 1085:1098 The MLP transcript was shown to be expressed in a variety of tissues; however, highest expression was observed in milk cells and was expressed constitutively from early to late lactation. 25245409 6 69 theme tissues 974:980 arg1 variety 963:969 a variety 961:969 a variety of tissues 961:980 The MLP transcript was shown to be expressed in a variety of tissues; however, highest expression was observed in milk cells and was expressed constitutively from early to late lactation. 25245409 6 69 theme tissues 974:980 arg1 tissues 974:980 tissues 974:980 tissues 974:980 The MLP transcript was shown to be expressed in a variety of tissues; however, highest expression was observed in milk cells and was expressed constitutively from early to late lactation. 25245409 6 70 theme highest 992:998 arg1 expression 1000:1009 highest expression 992:1009 highest expression 992:1009 The MLP transcript was shown to be expressed in a variety of tissues; however, highest expression was observed in milk cells and was expressed constitutively from early to late lactation. 25245409 8 71 theme Functional 1306:1315 arg1 analysis 1317:1324 Functional analysis 1306:1324 Functional analysis 1306:1324 Functional analysis revealed MLP antibacterial activity against both opportunistic pathogenic Staphylococcus aureus and commensal Enterococcus faecalis bacteria but showed no effect on Escherichia coli, Pseudomonas aeruginosa, Staphylococcus epidermidis, and Salmonella enterica. 25245409 1 72 theme other 223:227 arg1 mammals 229:235 other mammals 223:235 other mammals 223:235 Monotremes (platypus and echidna) are the descendants of the oldest ancestor of all extant mammals distinguished from other mammals by mode of reproduction. 25245409 7 73 theme glycosylated 1159:1170 arg1 it 1141:1142 it 1141:1142 it 1141:1142 Analysis of recombinant MLP showed that it is an N-linked glycosylated protein and biophysical studies predicted that MLP is an amphipathic, α-helical protein, a typical feature of antimicrobial proteins. 25245409 7 73 theme glycosylated 1159:1170 arg1 protein 1172:1178 an N-linked glycosylated protein 1147:1178 an N-linked glycosylated protein 1147:1178 Analysis of recombinant MLP showed that it is an N-linked glycosylated protein and biophysical studies predicted that MLP is an amphipathic, α-helical protein, a typical feature of antimicrobial proteins. 25245409 8 74 theme MLP 1335:1337 arg1 activity 1353:1360 MLP antibacterial activity 1335:1360 MLP antibacterial activity against both opportunistic pathogenic Staphylococcus aureus and commensal Enterococcus faecalis bacteria 1335:1465 Functional analysis revealed MLP antibacterial activity against both opportunistic pathogenic Staphylococcus aureus and commensal Enterococcus faecalis bacteria but showed no effect on Escherichia coli, Pseudomonas aeruginosa, Staphylococcus epidermidis, and Salmonella enterica. 25245409 4 75 theme major 768:772 arg1 protein 783:789 a major secreted protein 766:789 a major secreted protein in milk 766:797 Using transcriptome and mass spectrometry analysis of milk cells and milk proteins, respectively, a novel Monotreme Lactation Protein (MLP) was identified as a major secreted protein in milk. 25245409 4 75 theme major 768:772 arg1 Protein 734:740 a novel Monotreme Lactation Protein 706:740 a novel Monotreme Lactation Protein (MLP) 706:746 Using transcriptome and mass spectrometry analysis of milk cells and milk proteins, respectively, a novel Monotreme Lactation Protein (MLP) was identified as a major secreted protein in milk. 25245409 4 76 theme transcriptome 614:626 arg1 analysis 650:657 transcriptome and mass spectrometry analysis 614:657 analysis 650:657 Using transcriptome and mass spectrometry analysis of milk cells and milk proteins, respectively, a novel Monotreme Lactation Protein (MLP) was identified as a major secreted protein in milk. 25245409 1 77 dep Monotremes 105:114 arg1 echidna 130:136 echidna 130:136 echidna 130:136 Monotremes (platypus and echidna) are the descendants of the oldest ancestor of all extant mammals distinguished from other mammals by mode of reproduction. 25245409 1 77 dep Monotremes 105:114 arg1 platypus 117:124 platypus 117:124 platypus 117:124 Monotremes (platypus and echidna) are the descendants of the oldest ancestor of all extant mammals distinguished from other mammals by mode of reproduction. 25245409 1 77 dep Monotremes 105:114 arg1 Monotremes 105:114 Monotremes 105:114 Monotremes (platypus and echidna) 105:137 Monotremes (platypus and echidna) are the descendants of the oldest ancestor of all extant mammals distinguished from other mammals by mode of reproduction. 25245409 4 78 theme spectrometry 637:648 arg1 analysis 650:657 transcriptome and mass spectrometry analysis 614:657 analysis 650:657 Using transcriptome and mass spectrometry analysis of milk cells and milk proteins, respectively, a novel Monotreme Lactation Protein (MLP) was identified as a major secreted protein in milk. 25245409 0 79 theme monotreme 51:59 arg1 milk 61:64 monotreme milk 51:64 monotreme milk 51:64 Monotreme lactation protein is highly expressed in monotreme milk and provides antimicrobial protection. 25245409 9 80 from mammals 1700:1706 arg1 absent 1684:1689 absent 1684:1689 absent 1684:1689 Our data suggest that MLP is an evolutionarily ancient component of milk-mediated innate immunity absent in other mammals. 25245409 7 81 theme antimicrobial 1282:1294 arg1 proteins 1296:1303 antimicrobial proteins 1282:1303 antimicrobial proteins 1282:1303 Analysis of recombinant MLP showed that it is an N-linked glycosylated protein and biophysical studies predicted that MLP is an amphipathic, α-helical protein, a typical feature of antimicrobial proteins. 25245409 4 82 theme cells 667:671 arg1 analysis 650:657 transcriptome and mass spectrometry analysis 614:657 analysis 650:657 Using transcriptome and mass spectrometry analysis of milk cells and milk proteins, respectively, a novel Monotreme Lactation Protein (MLP) was identified as a major secreted protein in milk. 25245409 7 83 link N-linked 1150:1157 arg1 it 1141:1142 it 1141:1142 it 1141:1142 Analysis of recombinant MLP showed that it is an N-linked glycosylated protein and biophysical studies predicted that MLP is an amphipathic, α-helical protein, a typical feature of antimicrobial proteins. 25245409 7 83 link N-linked 1150:1157 arg1 protein 1172:1178 an N-linked glycosylated protein 1147:1178 an N-linked glycosylated protein 1147:1178 Analysis of recombinant MLP showed that it is an N-linked glycosylated protein and biophysical studies predicted that MLP is an amphipathic, α-helical protein, a typical feature of antimicrobial proteins. 24874551 4 0 theme conditional 826:836 arg1 mice 853:856 Fam20C conditional knockout (cKO) mice 819:856 Fam20C conditional knockout (cKO) mice 819:856 In this study, we crossed 3.6 kb Col1-Dmp1 transgenic mice with 3.6 kb Col1-Cre;Fam20Cfl/fl mice to overexpress Dmp1 in the mineralized tissues of Fam20C conditional knockout (cKO) mice. 24874551 1 1 theme small-integrin-binding 131:152 arg1 glycoproteins 171:183 N-linked glycoproteins 162:183 N-linked glycoproteins (SIBLINGs) 162:194 FAM20C is a kinase phosphorylating the small-integrin-binding ligand, N-linked glycoproteins (SIBLINGs), a group of extracellular matrix proteins that are essential for bone and dentin formation. 24874551 1 1 theme small-integrin-binding 131:152 arg1 group 199:203 a group 197:203 a group of extracellular matrix proteins that are essential for bone and dentin formation 197:285 FAM20C is a kinase phosphorylating the small-integrin-binding ligand, N-linked glycoproteins (SIBLINGs), a group of extracellular matrix proteins that are essential for bone and dentin formation. 24874551 1 1 theme small-integrin-binding 131:152 arg1 proteins 229:236 extracellular matrix proteins 208:236 extracellular matrix proteins that are essential for bone and dentin formation 208:285 FAM20C is a kinase phosphorylating the small-integrin-binding ligand, N-linked glycoproteins (SIBLINGs), a group of extracellular matrix proteins that are essential for bone and dentin formation. 24874551 1 1 theme small-integrin-binding 131:152 arg1 ligand 154:159 the small-integrin-binding ligand 127:159 the small-integrin-binding ligand 127:159 FAM20C is a kinase phosphorylating the small-integrin-binding ligand, N-linked glycoproteins (SIBLINGs), a group of extracellular matrix proteins that are essential for bone and dentin formation. 24874551 1 2 theme proteins 229:236 arg1 group 199:203 a group 197:203 a group of extracellular matrix proteins that are essential for bone and dentin formation 197:285 FAM20C is a kinase phosphorylating the small-integrin-binding ligand, N-linked glycoproteins (SIBLINGs), a group of extracellular matrix proteins that are essential for bone and dentin formation. 24874551 1 2 theme proteins 229:236 arg1 proteins 229:236 extracellular matrix proteins 208:236 extracellular matrix proteins that are essential for bone and dentin formation 208:285 FAM20C is a kinase phosphorylating the small-integrin-binding ligand, N-linked glycoproteins (SIBLINGs), a group of extracellular matrix proteins that are essential for bone and dentin formation. 24874551 1 2 theme proteins 229:236 arg1 ligand 154:159 the small-integrin-binding ligand 127:159 the small-integrin-binding ligand 127:159 FAM20C is a kinase phosphorylating the small-integrin-binding ligand, N-linked glycoproteins (SIBLINGs), a group of extracellular matrix proteins that are essential for bone and dentin formation. 24874551 5 3 theme phosphate 1064:1072 arg1 levels 1044:1049 the serum levels 1034:1049 the serum levels of FGF23 and phosphate in the Fam20C-cKO mice 1034:1095 X-ray, micro-computed tomography, serum biochemistry and histology analyses showed that expressing the Dmp1 transgene failed to rescue the bone and dentin defects, as well as the serum levels of FGF23 and phosphate in the Fam20C-cKO mice. 24874551 5 3 theme phosphate 1064:1072 arg1 defects 1014:1020 the bone and dentin defects 994:1020 the bone and dentin defects 994:1020 X-ray, micro-computed tomography, serum biochemistry and histology analyses showed that expressing the Dmp1 transgene failed to rescue the bone and dentin defects, as well as the serum levels of FGF23 and phosphate in the Fam20C-cKO mice. 24874551 4 4 theme Fam20C 819:824 arg1 mice 853:856 Fam20C conditional knockout (cKO) mice 819:856 Fam20C conditional knockout (cKO) mice 819:856 In this study, we crossed 3.6 kb Col1-Dmp1 transgenic mice with 3.6 kb Col1-Cre;Fam20Cfl/fl mice to overexpress Dmp1 in the mineralized tissues of Fam20C conditional knockout (cKO) mice. 24874551 4 5 theme knockout 838:845 arg1 mice 853:856 Fam20C conditional knockout (cKO) mice 819:856 Fam20C conditional knockout (cKO) mice 819:856 In this study, we crossed 3.6 kb Col1-Dmp1 transgenic mice with 3.6 kb Col1-Cre;Fam20Cfl/fl mice to overexpress Dmp1 in the mineralized tissues of Fam20C conditional knockout (cKO) mice. 24874551 6 6 theme bone 1222:1225 arg1 defects 1238:1244 the bone and dentin defects 1218:1244 the bone and dentin defects in the Fam20C-cKO mice 1218:1267 These results indicated that the downregulation of Dmp1 may not directly associate with, or significantly contribute to the bone and dentin defects in the Fam20C-cKO mice. 24874551 0 7 theme knockout 77:84 arg1 mice 86:89 Fam20C knockout mice 70:89 Fam20C knockout mice 70:89 Overexpression of Dmp1 fails to rescue the bone and dentin defects in Fam20C knockout mice. 24874551 5 8 theme histology 916:924 arg1 analyses 926:933 X-ray, micro-computed tomography, serum biochemistry and histology analyses 859:933 X-ray, micro-computed tomography, serum biochemistry and histology analyses 859:933 X-ray, micro-computed tomography, serum biochemistry and histology analyses showed that expressing the Dmp1 transgene failed to rescue the bone and dentin defects, as well as the serum levels of FGF23 and phosphate in the Fam20C-cKO mice. 24874551 3 9 theme SIBLINGs 513:520 arg1 failure 498:504 the assumed phosphorylation failure 470:504 the assumed phosphorylation failure of the SIBLINGs 470:520 While the assumed phosphorylation failure of the SIBLINGs is likely associated with the defects in the Fam20C-deficient mice, it remains unclear if the downregulation of Dmp1 contributes to these phenotypes. 24874551 0 10 theme Fam20C 70:75 arg1 mice 86:89 Fam20C knockout mice 70:89 Fam20C knockout mice 70:89 Overexpression of Dmp1 fails to rescue the bone and dentin defects in Fam20C knockout mice. 24874551 1 11 gly glycoproteins 171:183 arg1 glycoproteins 171:183 N-linked glycoproteins 162:183 N-linked glycoproteins (SIBLINGs) 162:194 FAM20C is a kinase phosphorylating the small-integrin-binding ligand, N-linked glycoproteins (SIBLINGs), a group of extracellular matrix proteins that are essential for bone and dentin formation. 24874551 1 11 gly glycoproteins 171:183 arg1 SIBLINGs 186:193 SIBLINGs 186:193 SIBLINGs 186:193 FAM20C is a kinase phosphorylating the small-integrin-binding ligand, N-linked glycoproteins (SIBLINGs), a group of extracellular matrix proteins that are essential for bone and dentin formation. 24874551 1 11 gly glycoproteins 171:183 arg1 ligand 154:159 the small-integrin-binding ligand 127:159 the small-integrin-binding ligand 127:159 FAM20C is a kinase phosphorylating the small-integrin-binding ligand, N-linked glycoproteins (SIBLINGs), a group of extracellular matrix proteins that are essential for bone and dentin formation. 24874551 2 12 theme Fam20Cfl/fl 324:334 arg1 mice 336:339 Sox2-Cre;Fam20Cfl/fl mice 315:339 Sox2-Cre;Fam20Cfl/fl mice 315:339 Previously, we showed that Sox2-Cre;Fam20Cfl/fl mice had bone and dentin defects, along with hypophosphatemia and significant downregulation of dentin matrix protein 1 (DMP1). 24874551 5 13 theme serum 1038:1042 arg1 levels 1044:1049 the serum levels 1034:1049 the serum levels of FGF23 and phosphate in the Fam20C-cKO mice 1034:1095 X-ray, micro-computed tomography, serum biochemistry and histology analyses showed that expressing the Dmp1 transgene failed to rescue the bone and dentin defects, as well as the serum levels of FGF23 and phosphate in the Fam20C-cKO mice. 24874551 4 14 theme mineralized 796:806 arg1 tissues 808:814 the mineralized tissues 792:814 the mineralized tissues of Fam20C conditional knockout (cKO) mice 792:856 In this study, we crossed 3.6 kb Col1-Dmp1 transgenic mice with 3.6 kb Col1-Cre;Fam20Cfl/fl mice to overexpress Dmp1 in the mineralized tissues of Fam20C conditional knockout (cKO) mice. 24874551 4 15 theme 3.6 kb 736:741 arg1 mice 764:767 3.6 kb Col1-Cre;Fam20Cfl/fl mice 736:767 3.6 kb Col1-Cre;Fam20Cfl/fl mice 736:767 In this study, we crossed 3.6 kb Col1-Dmp1 transgenic mice with 3.6 kb Col1-Cre;Fam20Cfl/fl mice to overexpress Dmp1 in the mineralized tissues of Fam20C conditional knockout (cKO) mice. 24874551 2 16 theme dentin 354:359 arg1 defects 361:367 bone and dentin defects 345:367 bone and dentin defects 345:367 Previously, we showed that Sox2-Cre;Fam20Cfl/fl mice had bone and dentin defects, along with hypophosphatemia and significant downregulation of dentin matrix protein 1 (DMP1). 24874551 5 17 from levels 1044:1049 arg1 mice 1092:1095 the Fam20C-cKO mice 1077:1095 the Fam20C-cKO mice 1077:1095 X-ray, micro-computed tomography, serum biochemistry and histology analyses showed that expressing the Dmp1 transgene failed to rescue the bone and dentin defects, as well as the serum levels of FGF23 and phosphate in the Fam20C-cKO mice. 24874551 2 18 contain had 341:343 arg2 defects 361:367 bone and dentin defects 345:367 bone and dentin defects 345:367 Previously, we showed that Sox2-Cre;Fam20Cfl/fl mice had bone and dentin defects, along with hypophosphatemia and significant downregulation of dentin matrix protein 1 (DMP1). 24874551 2 18 contain had 341:343 arg1 mice 336:339 Sox2-Cre;Fam20Cfl/fl mice 315:339 Sox2-Cre;Fam20Cfl/fl mice 315:339 Previously, we showed that Sox2-Cre;Fam20Cfl/fl mice had bone and dentin defects, along with hypophosphatemia and significant downregulation of dentin matrix protein 1 (DMP1). 24874551 5 19 theme Dmp1 962:965 arg1 transgene 967:975 the Dmp1 transgene 958:975 the Dmp1 transgene 958:975 X-ray, micro-computed tomography, serum biochemistry and histology analyses showed that expressing the Dmp1 transgene failed to rescue the bone and dentin defects, as well as the serum levels of FGF23 and phosphate in the Fam20C-cKO mice. 24874551 1 20 link N-linked 162:169 arg1 glycoproteins 171:183 N-linked glycoproteins 162:183 N-linked glycoproteins (SIBLINGs) 162:194 FAM20C is a kinase phosphorylating the small-integrin-binding ligand, N-linked glycoproteins (SIBLINGs), a group of extracellular matrix proteins that are essential for bone and dentin formation. 24874551 1 20 link N-linked 162:169 arg1 SIBLINGs 186:193 SIBLINGs 186:193 SIBLINGs 186:193 FAM20C is a kinase phosphorylating the small-integrin-binding ligand, N-linked glycoproteins (SIBLINGs), a group of extracellular matrix proteins that are essential for bone and dentin formation. 24874551 1 20 link N-linked 162:169 arg1 ligand 154:159 the small-integrin-binding ligand 127:159 the small-integrin-binding ligand 127:159 FAM20C is a kinase phosphorylating the small-integrin-binding ligand, N-linked glycoproteins (SIBLINGs), a group of extracellular matrix proteins that are essential for bone and dentin formation. 24874551 5 21 theme bone 998:1001 arg1 defects 1014:1020 the bone and dentin defects 994:1020 the bone and dentin defects 994:1020 X-ray, micro-computed tomography, serum biochemistry and histology analyses showed that expressing the Dmp1 transgene failed to rescue the bone and dentin defects, as well as the serum levels of FGF23 and phosphate in the Fam20C-cKO mice. 24874551 2 22 theme bone 345:348 arg1 defects 361:367 bone and dentin defects 345:367 bone and dentin defects 345:367 Previously, we showed that Sox2-Cre;Fam20Cfl/fl mice had bone and dentin defects, along with hypophosphatemia and significant downregulation of dentin matrix protein 1 (DMP1). 24874551 2 23 theme significant 402:412 arg1 downregulation 414:427 significant downregulation 402:427 significant downregulation of dentin matrix protein 1 (DMP1) 402:461 Previously, we showed that Sox2-Cre;Fam20Cfl/fl mice had bone and dentin defects, along with hypophosphatemia and significant downregulation of dentin matrix protein 1 (DMP1). 24874551 1 24 theme bone 261:264 arg1 formation 277:285 bone and dentin formation 261:285 bone and dentin formation 261:285 FAM20C is a kinase phosphorylating the small-integrin-binding ligand, N-linked glycoproteins (SIBLINGs), a group of extracellular matrix proteins that are essential for bone and dentin formation. 24874551 5 25 theme X-ray 859:863 arg1 analyses 926:933 X-ray, micro-computed tomography, serum biochemistry and histology analyses 859:933 X-ray, micro-computed tomography, serum biochemistry and histology analyses 859:933 X-ray, micro-computed tomography, serum biochemistry and histology analyses showed that expressing the Dmp1 transgene failed to rescue the bone and dentin defects, as well as the serum levels of FGF23 and phosphate in the Fam20C-cKO mice. 24874551 4 26 theme Col1-Dmp1 705:713 arg1 mice 726:729 3.6 kb Col1-Dmp1 transgenic mice 698:729 3.6 kb Col1-Dmp1 transgenic mice 698:729 In this study, we crossed 3.6 kb Col1-Dmp1 transgenic mice with 3.6 kb Col1-Cre;Fam20Cfl/fl mice to overexpress Dmp1 in the mineralized tissues of Fam20C conditional knockout (cKO) mice. 24874551 3 27 from defects 552:558 arg1 mice 584:587 the Fam20C-deficient mice 563:587 the Fam20C-deficient mice 563:587 While the assumed phosphorylation failure of the SIBLINGs is likely associated with the defects in the Fam20C-deficient mice, it remains unclear if the downregulation of Dmp1 contributes to these phenotypes. 24874551 0 28 theme Dmp1 18:21 arg1 Overexpression 0:13 Overexpression 0:13 Overexpression of Dmp1 0:21 Overexpression of Dmp1 fails to rescue the bone and dentin defects in Fam20C knockout mice. 24874551 5 29 theme serum 893:897 arg1 biochemistry 899:910 serum biochemistry 893:910 serum biochemistry 893:910 X-ray, micro-computed tomography, serum biochemistry and histology analyses showed that expressing the Dmp1 transgene failed to rescue the bone and dentin defects, as well as the serum levels of FGF23 and phosphate in the Fam20C-cKO mice. 24874551 4 30 theme 3.6 kb 698:703 arg1 mice 726:729 3.6 kb Col1-Dmp1 transgenic mice 698:729 3.6 kb Col1-Dmp1 transgenic mice 698:729 In this study, we crossed 3.6 kb Col1-Dmp1 transgenic mice with 3.6 kb Col1-Cre;Fam20Cfl/fl mice to overexpress Dmp1 in the mineralized tissues of Fam20C conditional knockout (cKO) mice. 24874551 1 31 theme dentin 270:275 arg1 formation 277:285 bone and dentin formation 261:285 bone and dentin formation 261:285 FAM20C is a kinase phosphorylating the small-integrin-binding ligand, N-linked glycoproteins (SIBLINGs), a group of extracellular matrix proteins that are essential for bone and dentin formation. 24874551 6 32 theme Fam20C-cKO 1253:1262 arg1 mice 1264:1267 the Fam20C-cKO mice 1249:1267 the Fam20C-cKO mice 1249:1267 These results indicated that the downregulation of Dmp1 may not directly associate with, or significantly contribute to the bone and dentin defects in the Fam20C-cKO mice. 24874551 0 33 from defects 59:65 arg1 mice 86:89 Fam20C knockout mice 70:89 Fam20C knockout mice 70:89 Overexpression of Dmp1 fails to rescue the bone and dentin defects in Fam20C knockout mice. 24874551 2 34 theme protein 446:452 arg1 downregulation 414:427 significant downregulation 402:427 significant downregulation of dentin matrix protein 1 (DMP1) 402:461 Previously, we showed that Sox2-Cre;Fam20Cfl/fl mice had bone and dentin defects, along with hypophosphatemia and significant downregulation of dentin matrix protein 1 (DMP1). 24874551 2 34 theme protein 446:452 arg1 hypophosphatemia 381:396 hypophosphatemia 381:396 hypophosphatemia 381:396 Previously, we showed that Sox2-Cre;Fam20Cfl/fl mice had bone and dentin defects, along with hypophosphatemia and significant downregulation of dentin matrix protein 1 (DMP1). 24874551 4 35 theme transgenic 715:724 arg1 mice 726:729 3.6 kb Col1-Dmp1 transgenic mice 698:729 3.6 kb Col1-Dmp1 transgenic mice 698:729 In this study, we crossed 3.6 kb Col1-Dmp1 transgenic mice with 3.6 kb Col1-Cre;Fam20Cfl/fl mice to overexpress Dmp1 in the mineralized tissues of Fam20C conditional knockout (cKO) mice. 24874551 2 36 theme matrix 439:444 arg1 protein 446:452 dentin matrix protein 1 432:454 dentin matrix protein 1 (DMP1) 432:461 Previously, we showed that Sox2-Cre;Fam20Cfl/fl mice had bone and dentin defects, along with hypophosphatemia and significant downregulation of dentin matrix protein 1 (DMP1). 24874551 2 36 theme matrix 439:444 arg1 DMP1 457:460 DMP1 457:460 DMP1 457:460 Previously, we showed that Sox2-Cre;Fam20Cfl/fl mice had bone and dentin defects, along with hypophosphatemia and significant downregulation of dentin matrix protein 1 (DMP1). 24874551 5 37 theme Fam20C-cKO 1081:1090 arg1 mice 1092:1095 the Fam20C-cKO mice 1077:1095 the Fam20C-cKO mice 1077:1095 X-ray, micro-computed tomography, serum biochemistry and histology analyses showed that expressing the Dmp1 transgene failed to rescue the bone and dentin defects, as well as the serum levels of FGF23 and phosphate in the Fam20C-cKO mice. 24874551 5 38 from defects 1014:1020 arg1 mice 1092:1095 the Fam20C-cKO mice 1077:1095 the Fam20C-cKO mice 1077:1095 X-ray, micro-computed tomography, serum biochemistry and histology analyses showed that expressing the Dmp1 transgene failed to rescue the bone and dentin defects, as well as the serum levels of FGF23 and phosphate in the Fam20C-cKO mice. 24874551 2 39 theme Sox2-Cre 315:322 arg1 mice 336:339 Sox2-Cre;Fam20Cfl/fl mice 315:339 Sox2-Cre;Fam20Cfl/fl mice 315:339 Previously, we showed that Sox2-Cre;Fam20Cfl/fl mice had bone and dentin defects, along with hypophosphatemia and significant downregulation of dentin matrix protein 1 (DMP1). 24874551 2 40 theme dentin 432:437 arg1 protein 446:452 dentin matrix protein 1 432:454 dentin matrix protein 1 (DMP1) 432:461 Previously, we showed that Sox2-Cre;Fam20Cfl/fl mice had bone and dentin defects, along with hypophosphatemia and significant downregulation of dentin matrix protein 1 (DMP1). 24874551 2 40 theme dentin 432:437 arg1 DMP1 457:460 DMP1 457:460 DMP1 457:460 Previously, we showed that Sox2-Cre;Fam20Cfl/fl mice had bone and dentin defects, along with hypophosphatemia and significant downregulation of dentin matrix protein 1 (DMP1). 24874551 4 41 theme cKO 848:850 arg1 mice 853:856 Fam20C conditional knockout (cKO) mice 819:856 Fam20C conditional knockout (cKO) mice 819:856 In this study, we crossed 3.6 kb Col1-Dmp1 transgenic mice with 3.6 kb Col1-Cre;Fam20Cfl/fl mice to overexpress Dmp1 in the mineralized tissues of Fam20C conditional knockout (cKO) mice. 24874551 3 42 theme Dmp1 634:637 arg1 downregulation 616:629 the downregulation 612:629 the downregulation of Dmp1 612:637 While the assumed phosphorylation failure of the SIBLINGs is likely associated with the defects in the Fam20C-deficient mice, it remains unclear if the downregulation of Dmp1 contributes to these phenotypes. 24874551 6 43 from defects 1238:1244 arg1 mice 1264:1267 the Fam20C-cKO mice 1249:1267 the Fam20C-cKO mice 1249:1267 These results indicated that the downregulation of Dmp1 may not directly associate with, or significantly contribute to the bone and dentin defects in the Fam20C-cKO mice. 24874551 6 44 theme dentin 1231:1236 arg1 defects 1238:1244 the bone and dentin defects 1218:1244 the bone and dentin defects in the Fam20C-cKO mice 1218:1267 These results indicated that the downregulation of Dmp1 may not directly associate with, or significantly contribute to the bone and dentin defects in the Fam20C-cKO mice. 24874551 6 45 theme Dmp1 1149:1152 arg1 downregulation 1131:1144 the downregulation 1127:1144 the downregulation of Dmp1 1127:1152 These results indicated that the downregulation of Dmp1 may not directly associate with, or significantly contribute to the bone and dentin defects in the Fam20C-cKO mice. 24874551 5 46 theme micro-computed 866:879 arg1 tomography 881:890 micro-computed tomography 866:890 micro-computed tomography 866:890 X-ray, micro-computed tomography, serum biochemistry and histology analyses showed that expressing the Dmp1 transgene failed to rescue the bone and dentin defects, as well as the serum levels of FGF23 and phosphate in the Fam20C-cKO mice. 24874551 5 47 theme biochemistry 899:910 arg1 analyses 926:933 X-ray, micro-computed tomography, serum biochemistry and histology analyses 859:933 X-ray, micro-computed tomography, serum biochemistry and histology analyses 859:933 X-ray, micro-computed tomography, serum biochemistry and histology analyses showed that expressing the Dmp1 transgene failed to rescue the bone and dentin defects, as well as the serum levels of FGF23 and phosphate in the Fam20C-cKO mice. 24874551 4 48 theme mice 853:856 arg1 tissues 808:814 the mineralized tissues 792:814 the mineralized tissues of Fam20C conditional knockout (cKO) mice 792:856 In this study, we crossed 3.6 kb Col1-Dmp1 transgenic mice with 3.6 kb Col1-Cre;Fam20Cfl/fl mice to overexpress Dmp1 in the mineralized tissues of Fam20C conditional knockout (cKO) mice. 24874551 5 49 theme dentin 1007:1012 arg1 defects 1014:1020 the bone and dentin defects 994:1020 the bone and dentin defects 994:1020 X-ray, micro-computed tomography, serum biochemistry and histology analyses showed that expressing the Dmp1 transgene failed to rescue the bone and dentin defects, as well as the serum levels of FGF23 and phosphate in the Fam20C-cKO mice. 24874551 4 50 theme Col1-Cre 743:750 arg1 mice 764:767 3.6 kb Col1-Cre;Fam20Cfl/fl mice 736:767 3.6 kb Col1-Cre;Fam20Cfl/fl mice 736:767 In this study, we crossed 3.6 kb Col1-Dmp1 transgenic mice with 3.6 kb Col1-Cre;Fam20Cfl/fl mice to overexpress Dmp1 in the mineralized tissues of Fam20C conditional knockout (cKO) mice. 24874551 5 51 theme tomography 881:890 arg1 analyses 926:933 X-ray, micro-computed tomography, serum biochemistry and histology analyses 859:933 X-ray, micro-computed tomography, serum biochemistry and histology analyses 859:933 X-ray, micro-computed tomography, serum biochemistry and histology analyses showed that expressing the Dmp1 transgene failed to rescue the bone and dentin defects, as well as the serum levels of FGF23 and phosphate in the Fam20C-cKO mice. 24874551 0 52 theme dentin 52:57 arg1 defects 59:65 the bone and dentin defects 39:65 the bone and dentin defects in Fam20C knockout mice 39:89 Overexpression of Dmp1 fails to rescue the bone and dentin defects in Fam20C knockout mice. 24874551 3 53 theme Fam20C-deficient 567:582 arg1 mice 584:587 the Fam20C-deficient mice 563:587 the Fam20C-deficient mice 563:587 While the assumed phosphorylation failure of the SIBLINGs is likely associated with the defects in the Fam20C-deficient mice, it remains unclear if the downregulation of Dmp1 contributes to these phenotypes. 24874551 3 54 theme assumed 474:480 arg1 failure 498:504 the assumed phosphorylation failure 470:504 the assumed phosphorylation failure of the SIBLINGs 470:520 While the assumed phosphorylation failure of the SIBLINGs is likely associated with the defects in the Fam20C-deficient mice, it remains unclear if the downregulation of Dmp1 contributes to these phenotypes. 24874551 1 55 theme N-linked 162:169 arg1 glycoproteins 171:183 N-linked glycoproteins 162:183 N-linked glycoproteins (SIBLINGs) 162:194 FAM20C is a kinase phosphorylating the small-integrin-binding ligand, N-linked glycoproteins (SIBLINGs), a group of extracellular matrix proteins that are essential for bone and dentin formation. 24874551 1 55 theme N-linked 162:169 arg1 SIBLINGs 186:193 SIBLINGs 186:193 SIBLINGs 186:193 FAM20C is a kinase phosphorylating the small-integrin-binding ligand, N-linked glycoproteins (SIBLINGs), a group of extracellular matrix proteins that are essential for bone and dentin formation. 24874551 1 55 theme N-linked 162:169 arg1 ligand 154:159 the small-integrin-binding ligand 127:159 the small-integrin-binding ligand 127:159 FAM20C is a kinase phosphorylating the small-integrin-binding ligand, N-linked glycoproteins (SIBLINGs), a group of extracellular matrix proteins that are essential for bone and dentin formation. 24874551 1 56 theme extracellular 208:220 arg1 proteins 229:236 extracellular matrix proteins 208:236 extracellular matrix proteins that are essential for bone and dentin formation 208:285 FAM20C is a kinase phosphorylating the small-integrin-binding ligand, N-linked glycoproteins (SIBLINGs), a group of extracellular matrix proteins that are essential for bone and dentin formation. 24874551 0 57 theme bone 43:46 arg1 defects 59:65 the bone and dentin defects 39:65 the bone and dentin defects in Fam20C knockout mice 39:89 Overexpression of Dmp1 fails to rescue the bone and dentin defects in Fam20C knockout mice. 24874551 5 58 theme FGF23 1054:1058 arg1 levels 1044:1049 the serum levels 1034:1049 the serum levels of FGF23 and phosphate in the Fam20C-cKO mice 1034:1095 X-ray, micro-computed tomography, serum biochemistry and histology analyses showed that expressing the Dmp1 transgene failed to rescue the bone and dentin defects, as well as the serum levels of FGF23 and phosphate in the Fam20C-cKO mice. 24874551 5 58 theme FGF23 1054:1058 arg1 defects 1014:1020 the bone and dentin defects 994:1020 the bone and dentin defects 994:1020 X-ray, micro-computed tomography, serum biochemistry and histology analyses showed that expressing the Dmp1 transgene failed to rescue the bone and dentin defects, as well as the serum levels of FGF23 and phosphate in the Fam20C-cKO mice. 24874551 4 59 theme Fam20Cfl/fl 752:762 arg1 mice 764:767 3.6 kb Col1-Cre;Fam20Cfl/fl mice 736:767 3.6 kb Col1-Cre;Fam20Cfl/fl mice 736:767 In this study, we crossed 3.6 kb Col1-Dmp1 transgenic mice with 3.6 kb Col1-Cre;Fam20Cfl/fl mice to overexpress Dmp1 in the mineralized tissues of Fam20C conditional knockout (cKO) mice. 24874551 3 60 theme phosphorylation 482:496 arg1 failure 498:504 the assumed phosphorylation failure 470:504 the assumed phosphorylation failure of the SIBLINGs 470:520 While the assumed phosphorylation failure of the SIBLINGs is likely associated with the defects in the Fam20C-deficient mice, it remains unclear if the downregulation of Dmp1 contributes to these phenotypes. 24874551 1 61 theme matrix 222:227 arg1 proteins 229:236 extracellular matrix proteins 208:236 extracellular matrix proteins that are essential for bone and dentin formation 208:285 FAM20C is a kinase phosphorylating the small-integrin-binding ligand, N-linked glycoproteins (SIBLINGs), a group of extracellular matrix proteins that are essential for bone and dentin formation. 24535270 6 0 theme N-linked 953:960 arg1 sites 976:980 three N-linked glycosylation sites 947:980 three N-linked glycosylation sites (N121V122S123,N173A174S175 and N673S674T675) 947:1025 Sequence analysis shows that the Aj-MTf contains two conserved domains, and the binding-iron (III) sites, including eight amino acid residues (D81,Y109,Y215,H283,D425,Y454,Y565 and H634) and three N-linked glycosylation sites (N121V122S123,N173A174S175 and N673S674T675). 24535270 6 0 theme N-linked 953:960 arg1 N673S674T675 1013:1024 N673S674T675 1013:1024 N673S674T675 1013:1024 Sequence analysis shows that the Aj-MTf contains two conserved domains, and the binding-iron (III) sites, including eight amino acid residues (D81,Y109,Y215,H283,D425,Y454,Y565 and H634) and three N-linked glycosylation sites (N121V122S123,N173A174S175 and N673S674T675). 24535270 6 0 theme N-linked 953:960 arg1 N173A174S175 996:1007 N173A174S175 996:1007 N173A174S175 996:1007 Sequence analysis shows that the Aj-MTf contains two conserved domains, and the binding-iron (III) sites, including eight amino acid residues (D81,Y109,Y215,H283,D425,Y454,Y565 and H634) and three N-linked glycosylation sites (N121V122S123,N173A174S175 and N673S674T675). 24535270 7 1 from expressions 1122:1132 arg1 fluid 1150:1154 the coelomic fluid 1137:1154 the coelomic fluid 1137:1154 Quantitative real-time polymerase chain reaction (qRT-PCR) analyses suggested that the Aj-MTf expressions in the coelomic fluid, body cavity wall and respiratory trees were significantly changed from 4 to 24 h post lipopolysaccharide (LPS) injection. 24535270 7 1 from expressions 1122:1132 arg1 wall 1169:1172 body cavity wall 1157:1172 body cavity wall 1157:1172 Quantitative real-time polymerase chain reaction (qRT-PCR) analyses suggested that the Aj-MTf expressions in the coelomic fluid, body cavity wall and respiratory trees were significantly changed from 4 to 24 h post lipopolysaccharide (LPS) injection. 24535270 7 1 from expressions 1122:1132 arg1 trees 1190:1194 respiratory trees 1178:1194 respiratory trees 1178:1194 Quantitative real-time polymerase chain reaction (qRT-PCR) analyses suggested that the Aj-MTf expressions in the coelomic fluid, body cavity wall and respiratory trees were significantly changed from 4 to 24 h post lipopolysaccharide (LPS) injection. 24535270 2 2 theme sea 264:266 arg1 cucumber 268:275 sea cucumber 264:275 sea cucumber 264:275 But the research about MTf in sea cucumber is limited till now. 24535270 8 3 theme LPS 1534:1536 arg1 injection 1538:1546 LPS injection 1534:1546 LPS injection 1534:1546 The mRNA levels of Aj-MTf in coelomic fluid was significantly up-regulated at 12 and 24 h in treatment group, and Aj-MTf shared a similar expression pattern with C-type lectin in coelomic fluid, while both genes appears to gradually increase after 4 h of LPS injection. 24535270 4 4 theme open 607:610 arg1 polypeptide 641:651 a polypeptide 639:651 a polypeptide of 727 amino acids 639:670 The full-length cDNA of Aj-MTf is 2,840 bp in length and contains a 2,184 bp open reading frame that encodes a polypeptide of 727 amino acids. 24535270 4 4 theme open 607:610 arg1 frame 620:624 a 2,184 bp open reading frame 596:624 a 2,184 bp open reading frame that encodes a polypeptide of 727 amino acids 596:670 The full-length cDNA of Aj-MTf is 2,840 bp in length and contains a 2,184 bp open reading frame that encodes a polypeptide of 727 amino acids. 24535270 0 5 theme Molecular 0:8 arg1 cloning 10:16 Molecular cloning 0:16 Molecular cloning 0:16 Molecular cloning, characterization and expression analysis of melanotransferrin from the sea cucumber Apostichopus japonicus. 24535270 1 6 theme transferrin 168:178 arg1 families 180:187 the transferrin families 164:187 the transferrin families 164:187 Melanotransferrin (MTf), a member of the transferrin families, plays an important role in immune response. 24535270 9 7 theme sea 1727:1729 arg1 cucumber 1731:1738 the sea cucumber 1723:1738 the sea cucumber 1723:1738 These results indicate that the Aj-MTf plays a pivotal role in immune responses to the LPS challenge in sea cucumber, and provide new information that it is complementary to the sea cucumber immune genes and initiate new researches concerning the genetic basis of the holothurian immune response. 24535270 2 8 theme till 288:291 arg1 research 242:249 the research 238:249 the research about MTf in sea cucumber 238:275 But the research about MTf in sea cucumber is limited till now. 24535270 2 8 theme till 288:291 arg1 now 293:295 limited till now 280:295 limited till now 280:295 But the research about MTf in sea cucumber is limited till now. 24535270 9 9 theme immune 1740:1745 arg1 genes 1747:1751 complementary to the sea cucumber immune genes 1706:1751 complementary to the sea cucumber immune genes 1706:1751 These results indicate that the Aj-MTf plays a pivotal role in immune responses to the LPS challenge in sea cucumber, and provide new information that it is complementary to the sea cucumber immune genes and initiate new researches concerning the genetic basis of the holothurian immune response. 24535270 6 10 theme acid 884:887 arg1 Y454 923:926 Y454 923:926 Y454 923:926 Sequence analysis shows that the Aj-MTf contains two conserved domains, and the binding-iron (III) sites, including eight amino acid residues (D81,Y109,Y215,H283,D425,Y454,Y565 and H634) and three N-linked glycosylation sites (N121V122S123,N173A174S175 and N673S674T675). 24535270 6 10 theme acid 884:887 arg1 residues 889:896 eight amino acid residues 872:896 eight amino acid residues (D81,Y109,Y215,H283,D425,Y454,Y565 and H634) 872:941 Sequence analysis shows that the Aj-MTf contains two conserved domains, and the binding-iron (III) sites, including eight amino acid residues (D81,Y109,Y215,H283,D425,Y454,Y565 and H634) and three N-linked glycosylation sites (N121V122S123,N173A174S175 and N673S674T675). 24535270 6 10 theme acid 884:887 arg1 Y565 928:931 Y565 928:931 Y565 928:931 Sequence analysis shows that the Aj-MTf contains two conserved domains, and the binding-iron (III) sites, including eight amino acid residues (D81,Y109,Y215,H283,D425,Y454,Y565 and H634) and three N-linked glycosylation sites (N121V122S123,N173A174S175 and N673S674T675). 24535270 6 10 theme acid 884:887 arg1 H283 913:916 H283 913:916 H283 913:916 Sequence analysis shows that the Aj-MTf contains two conserved domains, and the binding-iron (III) sites, including eight amino acid residues (D81,Y109,Y215,H283,D425,Y454,Y565 and H634) and three N-linked glycosylation sites (N121V122S123,N173A174S175 and N673S674T675). 24535270 6 10 theme acid 884:887 arg1 H634 937:940 H634 937:940 H634 937:940 Sequence analysis shows that the Aj-MTf contains two conserved domains, and the binding-iron (III) sites, including eight amino acid residues (D81,Y109,Y215,H283,D425,Y454,Y565 and H634) and three N-linked glycosylation sites (N121V122S123,N173A174S175 and N673S674T675). 24535270 6 10 theme acid 884:887 arg1 Y109 903:906 Y109 903:906 Y109 903:906 Sequence analysis shows that the Aj-MTf contains two conserved domains, and the binding-iron (III) sites, including eight amino acid residues (D81,Y109,Y215,H283,D425,Y454,Y565 and H634) and three N-linked glycosylation sites (N121V122S123,N173A174S175 and N673S674T675). 24535270 8 11 theme Aj-MTf 1298:1303 arg1 levels 1288:1293 The mRNA levels 1279:1293 The mRNA levels of Aj-MTf in coelomic fluid 1279:1321 The mRNA levels of Aj-MTf in coelomic fluid was significantly up-regulated at 12 and 24 h in treatment group, and Aj-MTf shared a similar expression pattern with C-type lectin in coelomic fluid, while both genes appears to gradually increase after 4 h of LPS injection. 24535270 7 12 theme lipopolysaccharide 1243:1260 arg1 injection 1268:1276 lipopolysaccharide (LPS) injection 1243:1276 lipopolysaccharide (LPS) injection 1243:1276 Quantitative real-time polymerase chain reaction (qRT-PCR) analyses suggested that the Aj-MTf expressions in the coelomic fluid, body cavity wall and respiratory trees were significantly changed from 4 to 24 h post lipopolysaccharide (LPS) injection. 24535270 4 13 theme 2,184 598:602 arg1 bp 604:605 bp 604:605 bp 604:605 The full-length cDNA of Aj-MTf is 2,840 bp in length and contains a 2,184 bp open reading frame that encodes a polypeptide of 727 amino acids. 24535270 7 14 dep 24 1233:1234 arg1 to 1230:1231 to 1230:1231 to 1230:1231 Quantitative real-time polymerase chain reaction (qRT-PCR) analyses suggested that the Aj-MTf expressions in the coelomic fluid, body cavity wall and respiratory trees were significantly changed from 4 to 24 h post lipopolysaccharide (LPS) injection. 24535270 8 15 theme coelomic 1308:1315 arg1 fluid 1317:1321 coelomic fluid 1308:1321 coelomic fluid 1308:1321 The mRNA levels of Aj-MTf in coelomic fluid was significantly up-regulated at 12 and 24 h in treatment group, and Aj-MTf shared a similar expression pattern with C-type lectin in coelomic fluid, while both genes appears to gradually increase after 4 h of LPS injection. 24535270 9 16 theme new 1766:1768 arg1 researches 1770:1779 new researches 1766:1779 new researches concerning the genetic basis of the holothurian immune response 1766:1843 These results indicate that the Aj-MTf plays a pivotal role in immune responses to the LPS challenge in sea cucumber, and provide new information that it is complementary to the sea cucumber immune genes and initiate new researches concerning the genetic basis of the holothurian immune response. 24535270 6 17 contain contains 796:803 arg2 sites 855:859 the binding-iron (III) sites 832:859 the binding-iron (III) sites 832:859 Sequence analysis shows that the Aj-MTf contains two conserved domains, and the binding-iron (III) sites, including eight amino acid residues (D81,Y109,Y215,H283,D425,Y454,Y565 and H634) and three N-linked glycosylation sites (N121V122S123,N173A174S175 and N673S674T675). 24535270 6 17 contain contains 796:803 arg2 domains 819:825 two conserved domains 805:825 two conserved domains 805:825 Sequence analysis shows that the Aj-MTf contains two conserved domains, and the binding-iron (III) sites, including eight amino acid residues (D81,Y109,Y215,H283,D425,Y454,Y565 and H634) and three N-linked glycosylation sites (N121V122S123,N173A174S175 and N673S674T675). 24535270 6 17 contain contains 796:803 arg2 residues 889:896 eight amino acid residues 872:896 eight amino acid residues (D81,Y109,Y215,H283,D425,Y454,Y565 and H634) 872:941 Sequence analysis shows that the Aj-MTf contains two conserved domains, and the binding-iron (III) sites, including eight amino acid residues (D81,Y109,Y215,H283,D425,Y454,Y565 and H634) and three N-linked glycosylation sites (N121V122S123,N173A174S175 and N673S674T675). 24535270 6 17 contain contains 796:803 arg1 Aj-MTf 789:794 the Aj-MTf 785:794 the Aj-MTf 785:794 Sequence analysis shows that the Aj-MTf contains two conserved domains, and the binding-iron (III) sites, including eight amino acid residues (D81,Y109,Y215,H283,D425,Y454,Y565 and H634) and three N-linked glycosylation sites (N121V122S123,N173A174S175 and N673S674T675). 24535270 6 17 contain contains 796:803 arg2 sites 976:980 three N-linked glycosylation sites 947:980 three N-linked glycosylation sites (N121V122S123,N173A174S175 and N673S674T675) 947:1025 Sequence analysis shows that the Aj-MTf contains two conserved domains, and the binding-iron (III) sites, including eight amino acid residues (D81,Y109,Y215,H283,D425,Y454,Y565 and H634) and three N-linked glycosylation sites (N121V122S123,N173A174S175 and N673S674T675). 24535270 4 18 theme acids 666:670 arg1 polypeptide 641:651 a polypeptide 639:651 a polypeptide of 727 amino acids 639:670 The full-length cDNA of Aj-MTf is 2,840 bp in length and contains a 2,184 bp open reading frame that encodes a polypeptide of 727 amino acids. 24535270 4 18 theme acids 666:670 arg1 frame 620:624 a 2,184 bp open reading frame 596:624 a 2,184 bp open reading frame that encodes a polypeptide of 727 amino acids 596:670 The full-length cDNA of Aj-MTf is 2,840 bp in length and contains a 2,184 bp open reading frame that encodes a polypeptide of 727 amino acids. 24535270 0 19 from cucumber 94:101 arg1 characterization 19:34 characterization 19:34 characterization 19:34 Molecular cloning, characterization and expression analysis of melanotransferrin from the sea cucumber Apostichopus japonicus. 24535270 0 19 from cucumber 94:101 arg1 analysis 51:58 expression analysis 40:58 expression analysis 40:58 Molecular cloning, characterization and expression analysis of melanotransferrin from the sea cucumber Apostichopus japonicus. 24535270 0 19 from cucumber 94:101 arg1 cloning 10:16 Molecular cloning 0:16 Molecular cloning 0:16 Molecular cloning, characterization and expression analysis of melanotransferrin from the sea cucumber Apostichopus japonicus. 24535270 9 20 theme genetic 1796:1802 arg1 basis 1804:1808 the genetic basis 1792:1808 the genetic basis of the holothurian immune response 1792:1843 These results indicate that the Aj-MTf plays a pivotal role in immune responses to the LPS challenge in sea cucumber, and provide new information that it is complementary to the sea cucumber immune genes and initiate new researches concerning the genetic basis of the holothurian immune response. 24535270 0 21 theme melanotransferrin 63:79 arg1 characterization 19:34 characterization 19:34 characterization 19:34 Molecular cloning, characterization and expression analysis of melanotransferrin from the sea cucumber Apostichopus japonicus. 24535270 0 21 theme melanotransferrin 63:79 arg1 analysis 51:58 expression analysis 40:58 expression analysis 40:58 Molecular cloning, characterization and expression analysis of melanotransferrin from the sea cucumber Apostichopus japonicus. 24535270 0 21 theme melanotransferrin 63:79 arg1 cloning 10:16 Molecular cloning 0:16 Molecular cloning 0:16 Molecular cloning, characterization and expression analysis of melanotransferrin from the sea cucumber Apostichopus japonicus. 24535270 6 22 gly glycosylation 962:974 arg2 N173A174S175 996:1007 N173A174S175 996:1007 N173A174S175 996:1007 Sequence analysis shows that the Aj-MTf contains two conserved domains, and the binding-iron (III) sites, including eight amino acid residues (D81,Y109,Y215,H283,D425,Y454,Y565 and H634) and three N-linked glycosylation sites (N121V122S123,N173A174S175 and N673S674T675). 24535270 6 22 gly glycosylation 962:974 arg2 three 947:951 three 947:951 three 947:951 Sequence analysis shows that the Aj-MTf contains two conserved domains, and the binding-iron (III) sites, including eight amino acid residues (D81,Y109,Y215,H283,D425,Y454,Y565 and H634) and three N-linked glycosylation sites (N121V122S123,N173A174S175 and N673S674T675). 24535270 6 22 gly glycosylation 962:974 arg2 sites 976:980 three N-linked glycosylation sites 947:980 three N-linked glycosylation sites (N121V122S123,N173A174S175 and N673S674T675) 947:1025 Sequence analysis shows that the Aj-MTf contains two conserved domains, and the binding-iron (III) sites, including eight amino acid residues (D81,Y109,Y215,H283,D425,Y454,Y565 and H634) and three N-linked glycosylation sites (N121V122S123,N173A174S175 and N673S674T675). 24535270 6 22 gly glycosylation 962:974 arg2 N673S674T675 1013:1024 N673S674T675 1013:1024 N673S674T675 1013:1024 Sequence analysis shows that the Aj-MTf contains two conserved domains, and the binding-iron (III) sites, including eight amino acid residues (D81,Y109,Y215,H283,D425,Y454,Y565 and H634) and three N-linked glycosylation sites (N121V122S123,N173A174S175 and N673S674T675). 24535270 3 23 theme Melanotransferrin 317:333 arg1 gene 344:347 the Melanotransferrin (Aj-MTf) gene 313:347 the Melanotransferrin (Aj-MTf) gene 313:347 In this study, the Melanotransferrin (Aj-MTf) gene was firstly cloned and characterized from the sea cucumber Apostichoupus japonicus by reverse transcriptase polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends. 24535270 9 24 theme holothurian 1817:1827 arg1 response 1836:1843 the holothurian immune response 1813:1843 the holothurian immune response 1813:1843 These results indicate that the Aj-MTf plays a pivotal role in immune responses to the LPS challenge in sea cucumber, and provide new information that it is complementary to the sea cucumber immune genes and initiate new researches concerning the genetic basis of the holothurian immune response. 24535270 3 25 theme cDNA 519:522 arg1 ends 524:527 cDNA ends 519:527 cDNA ends 519:527 In this study, the Melanotransferrin (Aj-MTf) gene was firstly cloned and characterized from the sea cucumber Apostichoupus japonicus by reverse transcriptase polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends. 24535270 9 26 theme response 1836:1843 arg1 basis 1804:1808 the genetic basis 1792:1808 the genetic basis of the holothurian immune response 1792:1843 These results indicate that the Aj-MTf plays a pivotal role in immune responses to the LPS challenge in sea cucumber, and provide new information that it is complementary to the sea cucumber immune genes and initiate new researches concerning the genetic basis of the holothurian immune response. 24535270 3 27 theme sea 395:397 arg1 cucumber 399:406 the sea cucumber 391:406 the sea cucumber 391:406 In this study, the Melanotransferrin (Aj-MTf) gene was firstly cloned and characterized from the sea cucumber Apostichoupus japonicus by reverse transcriptase polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends. 24535270 5 28 theme element-like 692:703 arg1 located 718:724 located 718:724 located 718:724 An iron-responsive element-like structure is located at the 5'-UTR of Aj-MTf cDNA. 24535270 5 28 theme element-like 692:703 arg1 structure 705:713 An iron-responsive element-like structure 673:713 An iron-responsive element-like structure 673:713 An iron-responsive element-like structure is located at the 5'-UTR of Aj-MTf cDNA. 24535270 0 29 dep cucumber 94:101 arg1 japonicus 116:124 the sea cucumber Apostichopus japonicus 86:124 the sea cucumber Apostichopus japonicus 86:124 Molecular cloning, characterization and expression analysis of melanotransferrin from the sea cucumber Apostichopus japonicus. 24535270 7 30 theme chain 1062:1066 arg1 qRT-PCR 1078:1084 qRT-PCR 1078:1084 qRT-PCR 1078:1084 Quantitative real-time polymerase chain reaction (qRT-PCR) analyses suggested that the Aj-MTf expressions in the coelomic fluid, body cavity wall and respiratory trees were significantly changed from 4 to 24 h post lipopolysaccharide (LPS) injection. 24535270 7 30 theme chain 1062:1066 arg1 reaction 1068:1075 Quantitative real-time polymerase chain reaction 1028:1075 Quantitative real-time polymerase chain reaction (qRT-PCR) analyses 1028:1094 Quantitative real-time polymerase chain reaction (qRT-PCR) analyses suggested that the Aj-MTf expressions in the coelomic fluid, body cavity wall and respiratory trees were significantly changed from 4 to 24 h post lipopolysaccharide (LPS) injection. 24535270 3 31 theme Aj-MTf 336:341 arg1 gene 344:347 the Melanotransferrin (Aj-MTf) gene 313:347 the Melanotransferrin (Aj-MTf) gene 313:347 In this study, the Melanotransferrin (Aj-MTf) gene was firstly cloned and characterized from the sea cucumber Apostichoupus japonicus by reverse transcriptase polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends. 24535270 7 32 theme real-time 1041:1049 arg1 qRT-PCR 1078:1084 qRT-PCR 1078:1084 qRT-PCR 1078:1084 Quantitative real-time polymerase chain reaction (qRT-PCR) analyses suggested that the Aj-MTf expressions in the coelomic fluid, body cavity wall and respiratory trees were significantly changed from 4 to 24 h post lipopolysaccharide (LPS) injection. 24535270 7 32 theme real-time 1041:1049 arg1 reaction 1068:1075 Quantitative real-time polymerase chain reaction 1028:1075 Quantitative real-time polymerase chain reaction (qRT-PCR) analyses 1028:1094 Quantitative real-time polymerase chain reaction (qRT-PCR) analyses suggested that the Aj-MTf expressions in the coelomic fluid, body cavity wall and respiratory trees were significantly changed from 4 to 24 h post lipopolysaccharide (LPS) injection. 24535270 7 33 theme respiratory 1178:1188 arg1 trees 1190:1194 respiratory trees 1178:1194 respiratory trees 1178:1194 Quantitative real-time polymerase chain reaction (qRT-PCR) analyses suggested that the Aj-MTf expressions in the coelomic fluid, body cavity wall and respiratory trees were significantly changed from 4 to 24 h post lipopolysaccharide (LPS) injection. 24535270 9 34 theme sea 1653:1655 arg1 cucumber 1657:1664 sea cucumber 1653:1664 sea cucumber 1653:1664 These results indicate that the Aj-MTf plays a pivotal role in immune responses to the LPS challenge in sea cucumber, and provide new information that it is complementary to the sea cucumber immune genes and initiate new researches concerning the genetic basis of the holothurian immune response. 24535270 8 35 theme similar 1409:1415 arg1 pattern 1428:1434 a similar expression pattern 1407:1434 a similar expression pattern 1407:1434 The mRNA levels of Aj-MTf in coelomic fluid was significantly up-regulated at 12 and 24 h in treatment group, and Aj-MTf shared a similar expression pattern with C-type lectin in coelomic fluid, while both genes appears to gradually increase after 4 h of LPS injection. 24535270 4 36 contain contains 587:594 arg2 frame 620:624 a 2,184 bp open reading frame 596:624 a 2,184 bp open reading frame that encodes a polypeptide of 727 amino acids 596:670 The full-length cDNA of Aj-MTf is 2,840 bp in length and contains a 2,184 bp open reading frame that encodes a polypeptide of 727 amino acids. 24535270 4 36 contain contains 587:594 arg1 bp 570:571 2,840 bp 564:571 2,840 bp in length 564:581 The full-length cDNA of Aj-MTf is 2,840 bp in length and contains a 2,184 bp open reading frame that encodes a polypeptide of 727 amino acids. 24535270 4 36 contain contains 587:594 arg1 cDNA 546:549 The full-length cDNA 530:549 The full-length cDNA of Aj-MTf 530:559 The full-length cDNA of Aj-MTf is 2,840 bp in length and contains a 2,184 bp open reading frame that encodes a polypeptide of 727 amino acids. 24535270 4 36 contain contains 587:594 arg2 polypeptide 641:651 a polypeptide 639:651 a polypeptide of 727 amino acids 639:670 The full-length cDNA of Aj-MTf is 2,840 bp in length and contains a 2,184 bp open reading frame that encodes a polypeptide of 727 amino acids. 24535270 6 37 dep sites 976:980 arg1 sites 976:980 three N-linked glycosylation sites 947:980 three N-linked glycosylation sites (N121V122S123,N173A174S175 and N673S674T675) 947:1025 Sequence analysis shows that the Aj-MTf contains two conserved domains, and the binding-iron (III) sites, including eight amino acid residues (D81,Y109,Y215,H283,D425,Y454,Y565 and H634) and three N-linked glycosylation sites (N121V122S123,N173A174S175 and N673S674T675). 24535270 6 37 dep sites 976:980 arg1 N673S674T675 1013:1024 N673S674T675 1013:1024 N673S674T675 1013:1024 Sequence analysis shows that the Aj-MTf contains two conserved domains, and the binding-iron (III) sites, including eight amino acid residues (D81,Y109,Y215,H283,D425,Y454,Y565 and H634) and three N-linked glycosylation sites (N121V122S123,N173A174S175 and N673S674T675). 24535270 6 37 dep sites 976:980 arg1 N173A174S175 996:1007 N173A174S175 996:1007 N173A174S175 996:1007 Sequence analysis shows that the Aj-MTf contains two conserved domains, and the binding-iron (III) sites, including eight amino acid residues (D81,Y109,Y215,H283,D425,Y454,Y565 and H634) and three N-linked glycosylation sites (N121V122S123,N173A174S175 and N673S674T675). 24535270 3 38 theme chain 468:472 arg1 RT-PCR 484:489 RT-PCR 484:489 RT-PCR 484:489 In this study, the Melanotransferrin (Aj-MTf) gene was firstly cloned and characterized from the sea cucumber Apostichoupus japonicus by reverse transcriptase polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends. 24535270 3 38 theme chain 468:472 arg1 reaction 474:481 reverse transcriptase polymerase chain reaction 435:481 reverse transcriptase polymerase chain reaction (RT-PCR) 435:490 In this study, the Melanotransferrin (Aj-MTf) gene was firstly cloned and characterized from the sea cucumber Apostichoupus japonicus by reverse transcriptase polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends. 24535270 5 39 theme Aj-MTf 743:748 arg1 cDNA 750:753 Aj-MTf cDNA 743:753 Aj-MTf cDNA 743:753 An iron-responsive element-like structure is located at the 5'-UTR of Aj-MTf cDNA. 24535270 7 40 theme body 1157:1160 arg1 wall 1169:1172 body cavity wall 1157:1172 body cavity wall 1157:1172 Quantitative real-time polymerase chain reaction (qRT-PCR) analyses suggested that the Aj-MTf expressions in the coelomic fluid, body cavity wall and respiratory trees were significantly changed from 4 to 24 h post lipopolysaccharide (LPS) injection. 24535270 8 41 theme mRNA 1283:1286 arg1 levels 1288:1293 The mRNA levels 1279:1293 The mRNA levels of Aj-MTf in coelomic fluid 1279:1321 The mRNA levels of Aj-MTf in coelomic fluid was significantly up-regulated at 12 and 24 h in treatment group, and Aj-MTf shared a similar expression pattern with C-type lectin in coelomic fluid, while both genes appears to gradually increase after 4 h of LPS injection. 24535270 3 42 theme transcriptase 443:455 arg1 RT-PCR 484:489 RT-PCR 484:489 RT-PCR 484:489 In this study, the Melanotransferrin (Aj-MTf) gene was firstly cloned and characterized from the sea cucumber Apostichoupus japonicus by reverse transcriptase polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends. 24535270 3 42 theme transcriptase 443:455 arg1 reaction 474:481 reverse transcriptase polymerase chain reaction 435:481 reverse transcriptase polymerase chain reaction (RT-PCR) 435:490 In this study, the Melanotransferrin (Aj-MTf) gene was firstly cloned and characterized from the sea cucumber Apostichoupus japonicus by reverse transcriptase polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends. 24535270 8 43 theme C-type 1441:1446 arg1 lectin 1448:1453 C-type lectin 1441:1453 C-type lectin in coelomic fluid 1441:1471 The mRNA levels of Aj-MTf in coelomic fluid was significantly up-regulated at 12 and 24 h in treatment group, and Aj-MTf shared a similar expression pattern with C-type lectin in coelomic fluid, while both genes appears to gradually increase after 4 h of LPS injection. 24535270 6 44 theme glycosylation 962:974 arg1 sites 976:980 three N-linked glycosylation sites 947:980 three N-linked glycosylation sites (N121V122S123,N173A174S175 and N673S674T675) 947:1025 Sequence analysis shows that the Aj-MTf contains two conserved domains, and the binding-iron (III) sites, including eight amino acid residues (D81,Y109,Y215,H283,D425,Y454,Y565 and H634) and three N-linked glycosylation sites (N121V122S123,N173A174S175 and N673S674T675). 24535270 6 44 theme glycosylation 962:974 arg1 N673S674T675 1013:1024 N673S674T675 1013:1024 N673S674T675 1013:1024 Sequence analysis shows that the Aj-MTf contains two conserved domains, and the binding-iron (III) sites, including eight amino acid residues (D81,Y109,Y215,H283,D425,Y454,Y565 and H634) and three N-linked glycosylation sites (N121V122S123,N173A174S175 and N673S674T675). 24535270 6 44 theme glycosylation 962:974 arg1 N173A174S175 996:1007 N173A174S175 996:1007 N173A174S175 996:1007 Sequence analysis shows that the Aj-MTf contains two conserved domains, and the binding-iron (III) sites, including eight amino acid residues (D81,Y109,Y215,H283,D425,Y454,Y565 and H634) and three N-linked glycosylation sites (N121V122S123,N173A174S175 and N673S674T675). 24535270 4 45 from bp 570:571 arg1 length 576:581 length 576:581 length 576:581 The full-length cDNA of Aj-MTf is 2,840 bp in length and contains a 2,184 bp open reading frame that encodes a polypeptide of 727 amino acids. 24535270 9 46 from challenge 1640:1648 arg1 cucumber 1657:1664 sea cucumber 1653:1664 sea cucumber 1653:1664 These results indicate that the Aj-MTf plays a pivotal role in immune responses to the LPS challenge in sea cucumber, and provide new information that it is complementary to the sea cucumber immune genes and initiate new researches concerning the genetic basis of the holothurian immune response. 24535270 6 47 theme Sequence 756:763 arg1 analysis 765:772 Sequence analysis 756:772 Sequence analysis 756:772 Sequence analysis shows that the Aj-MTf contains two conserved domains, and the binding-iron (III) sites, including eight amino acid residues (D81,Y109,Y215,H283,D425,Y454,Y565 and H634) and three N-linked glycosylation sites (N121V122S123,N173A174S175 and N673S674T675). 24535270 6 48 theme binding-iron 836:847 arg1 residues 889:896 eight amino acid residues 872:896 eight amino acid residues (D81,Y109,Y215,H283,D425,Y454,Y565 and H634) 872:941 Sequence analysis shows that the Aj-MTf contains two conserved domains, and the binding-iron (III) sites, including eight amino acid residues (D81,Y109,Y215,H283,D425,Y454,Y565 and H634) and three N-linked glycosylation sites (N121V122S123,N173A174S175 and N673S674T675). 24535270 6 48 theme binding-iron 836:847 arg1 sites 976:980 three N-linked glycosylation sites 947:980 three N-linked glycosylation sites (N121V122S123,N173A174S175 and N673S674T675) 947:1025 Sequence analysis shows that the Aj-MTf contains two conserved domains, and the binding-iron (III) sites, including eight amino acid residues (D81,Y109,Y215,H283,D425,Y454,Y565 and H634) and three N-linked glycosylation sites (N121V122S123,N173A174S175 and N673S674T675). 24535270 6 48 theme binding-iron 836:847 arg1 sites 855:859 the binding-iron (III) sites 832:859 the binding-iron (III) sites 832:859 Sequence analysis shows that the Aj-MTf contains two conserved domains, and the binding-iron (III) sites, including eight amino acid residues (D81,Y109,Y215,H283,D425,Y454,Y565 and H634) and three N-linked glycosylation sites (N121V122S123,N173A174S175 and N673S674T675). 24535270 9 49 theme complementary 1706:1718 arg1 genes 1747:1751 complementary to the sea cucumber immune genes 1706:1751 complementary to the sea cucumber immune genes 1706:1751 These results indicate that the Aj-MTf plays a pivotal role in immune responses to the LPS challenge in sea cucumber, and provide new information that it is complementary to the sea cucumber immune genes and initiate new researches concerning the genetic basis of the holothurian immune response. 24535270 4 50 theme Aj-MTf 554:559 arg1 bp 570:571 2,840 bp 564:571 2,840 bp in length 564:581 The full-length cDNA of Aj-MTf is 2,840 bp in length and contains a 2,184 bp open reading frame that encodes a polypeptide of 727 amino acids. 24535270 4 50 theme Aj-MTf 554:559 arg1 cDNA 546:549 The full-length cDNA 530:549 The full-length cDNA of Aj-MTf 530:559 The full-length cDNA of Aj-MTf is 2,840 bp in length and contains a 2,184 bp open reading frame that encodes a polypeptide of 727 amino acids. 24535270 3 51 theme rapid 496:500 arg1 amplification 502:514 rapid amplification 496:514 rapid amplification of cDNA ends 496:527 In this study, the Melanotransferrin (Aj-MTf) gene was firstly cloned and characterized from the sea cucumber Apostichoupus japonicus by reverse transcriptase polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends. 24535270 4 52 theme bp 604:605 arg1 polypeptide 641:651 a polypeptide 639:651 a polypeptide of 727 amino acids 639:670 The full-length cDNA of Aj-MTf is 2,840 bp in length and contains a 2,184 bp open reading frame that encodes a polypeptide of 727 amino acids. 24535270 4 52 theme bp 604:605 arg1 frame 620:624 a 2,184 bp open reading frame 596:624 a 2,184 bp open reading frame that encodes a polypeptide of 727 amino acids 596:670 The full-length cDNA of Aj-MTf is 2,840 bp in length and contains a 2,184 bp open reading frame that encodes a polypeptide of 727 amino acids. 24535270 8 53 theme injection 1538:1546 arg1 h 1529:1529 4 h 1527:1529 4 h of LPS injection 1527:1546 The mRNA levels of Aj-MTf in coelomic fluid was significantly up-regulated at 12 and 24 h in treatment group, and Aj-MTf shared a similar expression pattern with C-type lectin in coelomic fluid, while both genes appears to gradually increase after 4 h of LPS injection. 24535270 1 54 theme families 180:187 arg1 Melanotransferrin 127:143 Melanotransferrin 127:143 Melanotransferrin (MTf) 127:149 Melanotransferrin (MTf), a member of the transferrin families, plays an important role in immune response. 24535270 1 54 theme families 180:187 arg1 member 154:159 a member 152:159 a member of the transferrin families 152:187 Melanotransferrin (MTf), a member of the transferrin families, plays an important role in immune response. 24535270 4 55 theme reading 612:618 arg1 polypeptide 641:651 a polypeptide 639:651 a polypeptide of 727 amino acids 639:670 The full-length cDNA of Aj-MTf is 2,840 bp in length and contains a 2,184 bp open reading frame that encodes a polypeptide of 727 amino acids. 24535270 4 55 theme reading 612:618 arg1 frame 620:624 a 2,184 bp open reading frame 596:624 a 2,184 bp open reading frame that encodes a polypeptide of 727 amino acids 596:670 The full-length cDNA of Aj-MTf is 2,840 bp in length and contains a 2,184 bp open reading frame that encodes a polypeptide of 727 amino acids. 24535270 2 56 theme limited 280:286 arg1 research 242:249 the research 238:249 the research about MTf in sea cucumber 238:275 But the research about MTf in sea cucumber is limited till now. 24535270 2 56 theme limited 280:286 arg1 now 293:295 limited till now 280:295 limited till now 280:295 But the research about MTf in sea cucumber is limited till now. 24535270 8 57 from levels 1288:1293 arg1 fluid 1317:1321 coelomic fluid 1308:1321 coelomic fluid 1308:1321 The mRNA levels of Aj-MTf in coelomic fluid was significantly up-regulated at 12 and 24 h in treatment group, and Aj-MTf shared a similar expression pattern with C-type lectin in coelomic fluid, while both genes appears to gradually increase after 4 h of LPS injection. 24535270 8 58 from lectin 1448:1453 arg1 fluid 1467:1471 coelomic fluid 1458:1471 coelomic fluid 1458:1471 The mRNA levels of Aj-MTf in coelomic fluid was significantly up-regulated at 12 and 24 h in treatment group, and Aj-MTf shared a similar expression pattern with C-type lectin in coelomic fluid, while both genes appears to gradually increase after 4 h of LPS injection. 24535270 1 59 theme important 199:207 arg1 role 209:212 an important role 196:212 an important role 196:212 Melanotransferrin (MTf), a member of the transferrin families, plays an important role in immune response. 24535270 6 60 theme amino 878:882 arg1 Y454 923:926 Y454 923:926 Y454 923:926 Sequence analysis shows that the Aj-MTf contains two conserved domains, and the binding-iron (III) sites, including eight amino acid residues (D81,Y109,Y215,H283,D425,Y454,Y565 and H634) and three N-linked glycosylation sites (N121V122S123,N173A174S175 and N673S674T675). 24535270 6 60 theme amino 878:882 arg1 residues 889:896 eight amino acid residues 872:896 eight amino acid residues (D81,Y109,Y215,H283,D425,Y454,Y565 and H634) 872:941 Sequence analysis shows that the Aj-MTf contains two conserved domains, and the binding-iron (III) sites, including eight amino acid residues (D81,Y109,Y215,H283,D425,Y454,Y565 and H634) and three N-linked glycosylation sites (N121V122S123,N173A174S175 and N673S674T675). 24535270 6 60 theme amino 878:882 arg1 Y565 928:931 Y565 928:931 Y565 928:931 Sequence analysis shows that the Aj-MTf contains two conserved domains, and the binding-iron (III) sites, including eight amino acid residues (D81,Y109,Y215,H283,D425,Y454,Y565 and H634) and three N-linked glycosylation sites (N121V122S123,N173A174S175 and N673S674T675). 24535270 6 60 theme amino 878:882 arg1 H283 913:916 H283 913:916 H283 913:916 Sequence analysis shows that the Aj-MTf contains two conserved domains, and the binding-iron (III) sites, including eight amino acid residues (D81,Y109,Y215,H283,D425,Y454,Y565 and H634) and three N-linked glycosylation sites (N121V122S123,N173A174S175 and N673S674T675). 24535270 6 60 theme amino 878:882 arg1 H634 937:940 H634 937:940 H634 937:940 Sequence analysis shows that the Aj-MTf contains two conserved domains, and the binding-iron (III) sites, including eight amino acid residues (D81,Y109,Y215,H283,D425,Y454,Y565 and H634) and three N-linked glycosylation sites (N121V122S123,N173A174S175 and N673S674T675). 24535270 6 60 theme amino 878:882 arg1 Y109 903:906 Y109 903:906 Y109 903:906 Sequence analysis shows that the Aj-MTf contains two conserved domains, and the binding-iron (III) sites, including eight amino acid residues (D81,Y109,Y215,H283,D425,Y454,Y565 and H634) and three N-linked glycosylation sites (N121V122S123,N173A174S175 and N673S674T675). 24535270 9 61 theme pivotal 1596:1602 arg1 role 1604:1607 a pivotal role 1594:1607 a pivotal role 1594:1607 These results indicate that the Aj-MTf plays a pivotal role in immune responses to the LPS challenge in sea cucumber, and provide new information that it is complementary to the sea cucumber immune genes and initiate new researches concerning the genetic basis of the holothurian immune response. 24535270 6 62 dep residues 889:896 arg1 Y454 923:926 Y454 923:926 Y454 923:926 Sequence analysis shows that the Aj-MTf contains two conserved domains, and the binding-iron (III) sites, including eight amino acid residues (D81,Y109,Y215,H283,D425,Y454,Y565 and H634) and three N-linked glycosylation sites (N121V122S123,N173A174S175 and N673S674T675). 24535270 6 62 dep residues 889:896 arg1 residues 889:896 eight amino acid residues 872:896 eight amino acid residues (D81,Y109,Y215,H283,D425,Y454,Y565 and H634) 872:941 Sequence analysis shows that the Aj-MTf contains two conserved domains, and the binding-iron (III) sites, including eight amino acid residues (D81,Y109,Y215,H283,D425,Y454,Y565 and H634) and three N-linked glycosylation sites (N121V122S123,N173A174S175 and N673S674T675). 24535270 6 62 dep residues 889:896 arg1 Y565 928:931 Y565 928:931 Y565 928:931 Sequence analysis shows that the Aj-MTf contains two conserved domains, and the binding-iron (III) sites, including eight amino acid residues (D81,Y109,Y215,H283,D425,Y454,Y565 and H634) and three N-linked glycosylation sites (N121V122S123,N173A174S175 and N673S674T675). 24535270 6 62 dep residues 889:896 arg1 H283 913:916 H283 913:916 H283 913:916 Sequence analysis shows that the Aj-MTf contains two conserved domains, and the binding-iron (III) sites, including eight amino acid residues (D81,Y109,Y215,H283,D425,Y454,Y565 and H634) and three N-linked glycosylation sites (N121V122S123,N173A174S175 and N673S674T675). 24535270 6 62 dep residues 889:896 arg1 H634 937:940 H634 937:940 H634 937:940 Sequence analysis shows that the Aj-MTf contains two conserved domains, and the binding-iron (III) sites, including eight amino acid residues (D81,Y109,Y215,H283,D425,Y454,Y565 and H634) and three N-linked glycosylation sites (N121V122S123,N173A174S175 and N673S674T675). 24535270 6 62 dep residues 889:896 arg1 Y109 903:906 Y109 903:906 Y109 903:906 Sequence analysis shows that the Aj-MTf contains two conserved domains, and the binding-iron (III) sites, including eight amino acid residues (D81,Y109,Y215,H283,D425,Y454,Y565 and H634) and three N-linked glycosylation sites (N121V122S123,N173A174S175 and N673S674T675). 24535270 5 63 located located 718:724 arg2 located 718:724 located 718:724 located 718:724 An iron-responsive element-like structure is located at the 5'-UTR of Aj-MTf cDNA. 24535270 5 63 located located 718:724 arg1 5'-UTR 733:738 the 5'-UTR 729:738 the 5'-UTR of Aj-MTf cDNA 729:753 An iron-responsive element-like structure is located at the 5'-UTR of Aj-MTf cDNA. 24535270 5 63 located located 718:724 arg2 structure 705:713 An iron-responsive element-like structure 673:713 An iron-responsive element-like structure 673:713 An iron-responsive element-like structure is located at the 5'-UTR of Aj-MTf cDNA. 24535270 3 64 theme ends 524:527 arg1 RT-PCR 484:489 RT-PCR 484:489 RT-PCR 484:489 In this study, the Melanotransferrin (Aj-MTf) gene was firstly cloned and characterized from the sea cucumber Apostichoupus japonicus by reverse transcriptase polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends. 24535270 3 64 theme ends 524:527 arg1 reaction 474:481 reverse transcriptase polymerase chain reaction 435:481 reverse transcriptase polymerase chain reaction (RT-PCR) 435:490 In this study, the Melanotransferrin (Aj-MTf) gene was firstly cloned and characterized from the sea cucumber Apostichoupus japonicus by reverse transcriptase polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends. 24535270 3 64 theme ends 524:527 arg1 amplification 502:514 rapid amplification 496:514 rapid amplification of cDNA ends 496:527 In this study, the Melanotransferrin (Aj-MTf) gene was firstly cloned and characterized from the sea cucumber Apostichoupus japonicus by reverse transcriptase polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends. 24535270 4 65 theme amino 660:664 arg1 acids 666:670 727 amino acids 656:670 727 amino acids 656:670 The full-length cDNA of Aj-MTf is 2,840 bp in length and contains a 2,184 bp open reading frame that encodes a polypeptide of 727 amino acids. 24535270 0 66 theme sea 90:92 arg1 cucumber 94:101 the sea cucumber Apostichopus japonicus 86:124 the sea cucumber Apostichopus japonicus 86:124 Molecular cloning, characterization and expression analysis of melanotransferrin from the sea cucumber Apostichopus japonicus. 24535270 0 67 theme Apostichopus 103:114 arg1 cucumber 94:101 the sea cucumber Apostichopus japonicus 86:124 the sea cucumber Apostichopus japonicus 86:124 Molecular cloning, characterization and expression analysis of melanotransferrin from the sea cucumber Apostichopus japonicus. 24535270 5 68 from 5'-UTR 733:738 arg1 located 718:724 located 718:724 located 718:724 An iron-responsive element-like structure is located at the 5'-UTR of Aj-MTf cDNA. 24535270 5 68 from 5'-UTR 733:738 arg1 structure 705:713 An iron-responsive element-like structure 673:713 An iron-responsive element-like structure 673:713 An iron-responsive element-like structure is located at the 5'-UTR of Aj-MTf cDNA. 24535270 8 69 theme treatment 1372:1380 arg1 group 1382:1386 treatment group 1372:1386 treatment group 1372:1386 The mRNA levels of Aj-MTf in coelomic fluid was significantly up-regulated at 12 and 24 h in treatment group, and Aj-MTf shared a similar expression pattern with C-type lectin in coelomic fluid, while both genes appears to gradually increase after 4 h of LPS injection. 24535270 9 70 theme immune 1829:1834 arg1 response 1836:1843 the holothurian immune response 1813:1843 the holothurian immune response 1813:1843 These results indicate that the Aj-MTf plays a pivotal role in immune responses to the LPS challenge in sea cucumber, and provide new information that it is complementary to the sea cucumber immune genes and initiate new researches concerning the genetic basis of the holothurian immune response. 24535270 5 71 theme iron-responsive 676:690 arg1 located 718:724 located 718:724 located 718:724 An iron-responsive element-like structure is located at the 5'-UTR of Aj-MTf cDNA. 24535270 5 71 theme iron-responsive 676:690 arg1 structure 705:713 An iron-responsive element-like structure 673:713 An iron-responsive element-like structure 673:713 An iron-responsive element-like structure is located at the 5'-UTR of Aj-MTf cDNA. 24535270 9 72 theme immune 1612:1617 arg1 responses 1619:1627 immune responses 1612:1627 immune responses to the LPS challenge in sea cucumber 1612:1664 These results indicate that the Aj-MTf plays a pivotal role in immune responses to the LPS challenge in sea cucumber, and provide new information that it is complementary to the sea cucumber immune genes and initiate new researches concerning the genetic basis of the holothurian immune response. 24535270 7 73 theme reaction 1068:1075 arg1 analyses 1087:1094 Quantitative real-time polymerase chain reaction (qRT-PCR) analyses 1028:1094 Quantitative real-time polymerase chain reaction (qRT-PCR) analyses 1028:1094 Quantitative real-time polymerase chain reaction (qRT-PCR) analyses suggested that the Aj-MTf expressions in the coelomic fluid, body cavity wall and respiratory trees were significantly changed from 4 to 24 h post lipopolysaccharide (LPS) injection. 24535270 5 74 theme cDNA 750:753 arg1 5'-UTR 733:738 the 5'-UTR 729:738 the 5'-UTR of Aj-MTf cDNA 729:753 An iron-responsive element-like structure is located at the 5'-UTR of Aj-MTf cDNA. 24535270 7 75 theme Quantitative 1028:1039 arg1 qRT-PCR 1078:1084 qRT-PCR 1078:1084 qRT-PCR 1078:1084 Quantitative real-time polymerase chain reaction (qRT-PCR) analyses suggested that the Aj-MTf expressions in the coelomic fluid, body cavity wall and respiratory trees were significantly changed from 4 to 24 h post lipopolysaccharide (LPS) injection. 24535270 7 75 theme Quantitative 1028:1039 arg1 reaction 1068:1075 Quantitative real-time polymerase chain reaction 1028:1075 Quantitative real-time polymerase chain reaction (qRT-PCR) analyses 1028:1094 Quantitative real-time polymerase chain reaction (qRT-PCR) analyses suggested that the Aj-MTf expressions in the coelomic fluid, body cavity wall and respiratory trees were significantly changed from 4 to 24 h post lipopolysaccharide (LPS) injection. 24535270 9 76 theme LPS 1636:1638 arg1 challenge 1640:1648 the LPS challenge 1632:1648 the LPS challenge in sea cucumber 1632:1664 These results indicate that the Aj-MTf plays a pivotal role in immune responses to the LPS challenge in sea cucumber, and provide new information that it is complementary to the sea cucumber immune genes and initiate new researches concerning the genetic basis of the holothurian immune response. 24535270 4 77 theme full-length 534:544 arg1 bp 570:571 2,840 bp 564:571 2,840 bp in length 564:581 The full-length cDNA of Aj-MTf is 2,840 bp in length and contains a 2,184 bp open reading frame that encodes a polypeptide of 727 amino acids. 24535270 4 77 theme full-length 534:544 arg1 cDNA 546:549 The full-length cDNA 530:549 The full-length cDNA of Aj-MTf 530:559 The full-length cDNA of Aj-MTf is 2,840 bp in length and contains a 2,184 bp open reading frame that encodes a polypeptide of 727 amino acids. 24535270 3 78 theme reverse 435:441 arg1 RT-PCR 484:489 RT-PCR 484:489 RT-PCR 484:489 In this study, the Melanotransferrin (Aj-MTf) gene was firstly cloned and characterized from the sea cucumber Apostichoupus japonicus by reverse transcriptase polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends. 24535270 3 78 theme reverse 435:441 arg1 reaction 474:481 reverse transcriptase polymerase chain reaction 435:481 reverse transcriptase polymerase chain reaction (RT-PCR) 435:490 In this study, the Melanotransferrin (Aj-MTf) gene was firstly cloned and characterized from the sea cucumber Apostichoupus japonicus by reverse transcriptase polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends. 24535270 0 79 theme expression 40:49 arg1 analysis 51:58 expression analysis 40:58 expression analysis 40:58 Molecular cloning, characterization and expression analysis of melanotransferrin from the sea cucumber Apostichopus japonicus. 24535270 6 80 theme conserved 809:817 arg1 residues 889:896 eight amino acid residues 872:896 eight amino acid residues (D81,Y109,Y215,H283,D425,Y454,Y565 and H634) 872:941 Sequence analysis shows that the Aj-MTf contains two conserved domains, and the binding-iron (III) sites, including eight amino acid residues (D81,Y109,Y215,H283,D425,Y454,Y565 and H634) and three N-linked glycosylation sites (N121V122S123,N173A174S175 and N673S674T675). 24535270 6 80 theme conserved 809:817 arg1 sites 976:980 three N-linked glycosylation sites 947:980 three N-linked glycosylation sites (N121V122S123,N173A174S175 and N673S674T675) 947:1025 Sequence analysis shows that the Aj-MTf contains two conserved domains, and the binding-iron (III) sites, including eight amino acid residues (D81,Y109,Y215,H283,D425,Y454,Y565 and H634) and three N-linked glycosylation sites (N121V122S123,N173A174S175 and N673S674T675). 24535270 6 80 theme conserved 809:817 arg1 domains 819:825 two conserved domains 805:825 two conserved domains 805:825 Sequence analysis shows that the Aj-MTf contains two conserved domains, and the binding-iron (III) sites, including eight amino acid residues (D81,Y109,Y215,H283,D425,Y454,Y565 and H634) and three N-linked glycosylation sites (N121V122S123,N173A174S175 and N673S674T675). 24535270 2 81 from research 242:249 arg1 cucumber 268:275 sea cucumber 264:275 sea cucumber 264:275 But the research about MTf in sea cucumber is limited till now. 24535270 7 82 theme cavity 1162:1167 arg1 wall 1169:1172 body cavity wall 1157:1172 body cavity wall 1157:1172 Quantitative real-time polymerase chain reaction (qRT-PCR) analyses suggested that the Aj-MTf expressions in the coelomic fluid, body cavity wall and respiratory trees were significantly changed from 4 to 24 h post lipopolysaccharide (LPS) injection. 24535270 8 83 theme expression 1417:1426 arg1 pattern 1428:1434 a similar expression pattern 1407:1434 a similar expression pattern 1407:1434 The mRNA levels of Aj-MTf in coelomic fluid was significantly up-regulated at 12 and 24 h in treatment group, and Aj-MTf shared a similar expression pattern with C-type lectin in coelomic fluid, while both genes appears to gradually increase after 4 h of LPS injection. 24535270 6 84 link N-linked 953:960 arg1 sites 976:980 three N-linked glycosylation sites 947:980 three N-linked glycosylation sites (N121V122S123,N173A174S175 and N673S674T675) 947:1025 Sequence analysis shows that the Aj-MTf contains two conserved domains, and the binding-iron (III) sites, including eight amino acid residues (D81,Y109,Y215,H283,D425,Y454,Y565 and H634) and three N-linked glycosylation sites (N121V122S123,N173A174S175 and N673S674T675). 24535270 6 84 link N-linked 953:960 arg1 N673S674T675 1013:1024 N673S674T675 1013:1024 N673S674T675 1013:1024 Sequence analysis shows that the Aj-MTf contains two conserved domains, and the binding-iron (III) sites, including eight amino acid residues (D81,Y109,Y215,H283,D425,Y454,Y565 and H634) and three N-linked glycosylation sites (N121V122S123,N173A174S175 and N673S674T675). 24535270 6 84 link N-linked 953:960 arg1 N173A174S175 996:1007 N173A174S175 996:1007 N173A174S175 996:1007 Sequence analysis shows that the Aj-MTf contains two conserved domains, and the binding-iron (III) sites, including eight amino acid residues (D81,Y109,Y215,H283,D425,Y454,Y565 and H634) and three N-linked glycosylation sites (N121V122S123,N173A174S175 and N673S674T675). 24535270 7 85 theme coelomic 1141:1148 arg1 fluid 1150:1154 the coelomic fluid 1137:1154 the coelomic fluid 1137:1154 Quantitative real-time polymerase chain reaction (qRT-PCR) analyses suggested that the Aj-MTf expressions in the coelomic fluid, body cavity wall and respiratory trees were significantly changed from 4 to 24 h post lipopolysaccharide (LPS) injection. 24535270 3 86 theme polymerase 457:466 arg1 RT-PCR 484:489 RT-PCR 484:489 RT-PCR 484:489 In this study, the Melanotransferrin (Aj-MTf) gene was firstly cloned and characterized from the sea cucumber Apostichoupus japonicus by reverse transcriptase polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends. 24535270 3 86 theme polymerase 457:466 arg1 reaction 474:481 reverse transcriptase polymerase chain reaction 435:481 reverse transcriptase polymerase chain reaction (RT-PCR) 435:490 In this study, the Melanotransferrin (Aj-MTf) gene was firstly cloned and characterized from the sea cucumber Apostichoupus japonicus by reverse transcriptase polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends. 24535270 1 87 theme immune 217:222 arg1 response 224:231 immune response 217:231 immune response 217:231 Melanotransferrin (MTf), a member of the transferrin families, plays an important role in immune response. 24535270 9 88 theme new 1679:1681 arg1 information 1683:1693 new information that it is complementary to the sea cucumber immune genes 1679:1751 new information that it is complementary to the sea cucumber immune genes 1679:1751 These results indicate that the Aj-MTf plays a pivotal role in immune responses to the LPS challenge in sea cucumber, and provide new information that it is complementary to the sea cucumber immune genes and initiate new researches concerning the genetic basis of the holothurian immune response. 24535270 8 89 theme coelomic 1458:1465 arg1 fluid 1467:1471 coelomic fluid 1458:1471 coelomic fluid 1458:1471 The mRNA levels of Aj-MTf in coelomic fluid was significantly up-regulated at 12 and 24 h in treatment group, and Aj-MTf shared a similar expression pattern with C-type lectin in coelomic fluid, while both genes appears to gradually increase after 4 h of LPS injection. 24535270 7 90 theme polymerase 1051:1060 arg1 qRT-PCR 1078:1084 qRT-PCR 1078:1084 qRT-PCR 1078:1084 Quantitative real-time polymerase chain reaction (qRT-PCR) analyses suggested that the Aj-MTf expressions in the coelomic fluid, body cavity wall and respiratory trees were significantly changed from 4 to 24 h post lipopolysaccharide (LPS) injection. 24535270 7 90 theme polymerase 1051:1060 arg1 reaction 1068:1075 Quantitative real-time polymerase chain reaction 1028:1075 Quantitative real-time polymerase chain reaction (qRT-PCR) analyses 1028:1094 Quantitative real-time polymerase chain reaction (qRT-PCR) analyses suggested that the Aj-MTf expressions in the coelomic fluid, body cavity wall and respiratory trees were significantly changed from 4 to 24 h post lipopolysaccharide (LPS) injection. 24535270 7 91 theme Aj-MTf 1115:1120 arg1 expressions 1122:1132 the Aj-MTf expressions 1111:1132 the Aj-MTf expressions in the coelomic fluid, body cavity wall and respiratory trees 1111:1194 Quantitative real-time polymerase chain reaction (qRT-PCR) analyses suggested that the Aj-MTf expressions in the coelomic fluid, body cavity wall and respiratory trees were significantly changed from 4 to 24 h post lipopolysaccharide (LPS) injection. 24520323 9 0 theme dose-dependent 1647:1660 arg1 defibrinogenation 1662:1678 dose-dependent defibrinogenation 1647:1678 dose-dependent defibrinogenation 1647:1678 In vitro these protease isoenzymes induce blood coagulation through factor V activation, whereas in vivo they provoke dose-dependent defibrinogenation and anticoagulant activity in the mouse model. 24520323 7 1 theme fibrinogen 1235:1244 arg1 pattern 1258:1264 fibrinogen degradation pattern 1235:1264 fibrinogen degradation pattern 1235:1264 On the basis of fibrinogen degradation pattern, they may be classified as A/B serine proteases isolated from snake venom. 24520323 0 2 theme enzymatic 181:189 arg1 activity 191:198 enzymatic activity 181:198 enzymatic activity 181:198 The pro-coagulant fibrinogenolytic serine protease isoenzymes purified from Daboia russelii russelii venom coagulate the blood through factor V activation: role of glycosylation on enzymatic activity. 24520323 3 3 theme N-terminal 460:469 arg1 isoenzymes 505:514 these serine protease isoenzymes 483:514 these serine protease isoenzymes 483:514 The first 10 N-terminal residues of these serine protease isoenzymes showed significant sequence homology with N-terminal sequences of snake venom thrombin-like and factor V-activating serine proteases, which was reconfirmed by peptide mass fingerprinting analysis. 24520323 3 3 theme N-terminal 460:469 arg1 residues 471:478 The first 10 N-terminal residues 447:478 The first 10 N-terminal residues of these serine protease isoenzymes 447:514 The first 10 N-terminal residues of these serine protease isoenzymes showed significant sequence homology with N-terminal sequences of snake venom thrombin-like and factor V-activating serine proteases, which was reconfirmed by peptide mass fingerprinting analysis. 24520323 6 4 theme units/mg 1187:1194 arg1 protein 1196:1202 111.0 to 125.5 units/mg protein 1172:1202 111.0 to 125.5 units/mg protein 1172:1202 Their Km and Vmax values towards fibrinogen were determined in the range of 6.6 to 10.5 µM and 111.0 to 125.5 units/mg protein, respectively. 24520323 9 5 theme blood 1571:1575 arg1 coagulation 1577:1587 blood coagulation 1571:1587 blood coagulation 1571:1587 In vitro these protease isoenzymes induce blood coagulation through factor V activation, whereas in vivo they provoke dose-dependent defibrinogenation and anticoagulant activity in the mouse model. 24520323 3 6 theme isoenzymes 505:514 arg1 isoenzymes 505:514 these serine protease isoenzymes 483:514 these serine protease isoenzymes 483:514 The first 10 N-terminal residues of these serine protease isoenzymes showed significant sequence homology with N-terminal sequences of snake venom thrombin-like and factor V-activating serine proteases, which was reconfirmed by peptide mass fingerprinting analysis. 24520323 3 6 theme isoenzymes 505:514 arg1 residues 471:478 The first 10 N-terminal residues 447:478 The first 10 N-terminal residues of these serine protease isoenzymes 447:514 The first 10 N-terminal residues of these serine protease isoenzymes showed significant sequence homology with N-terminal sequences of snake venom thrombin-like and factor V-activating serine proteases, which was reconfirmed by peptide mass fingerprinting analysis. 24520323 6 7 dep 10.5 1160:1163 arg1 to 1157:1158 to 1157:1158 to 1157:1158 Their Km and Vmax values towards fibrinogen were determined in the range of 6.6 to 10.5 µM and 111.0 to 125.5 units/mg protein, respectively. 24520323 1 8 from victim 281:286 arg1 variety 253:259 a variety 251:259 a variety of toxic effects in victim 251:286 Proteases from Russell's viper venom (RVV) induce a variety of toxic effects in victim. 24520323 1 8 from victim 281:286 arg1 effects 270:276 toxic effects 264:276 toxic effects in victim 264:286 Proteases from Russell's viper venom (RVV) induce a variety of toxic effects in victim. 24520323 3 9 theme serine 489:494 arg1 isoenzymes 505:514 these serine protease isoenzymes 483:514 these serine protease isoenzymes 483:514 The first 10 N-terminal residues of these serine protease isoenzymes showed significant sequence homology with N-terminal sequences of snake venom thrombin-like and factor V-activating serine proteases, which was reconfirmed by peptide mass fingerprinting analysis. 24520323 8 10 gly deglycosylated 1430:1443 arg1 enzymes 1445:1451 partially deglycosylated enzymes 1420:1451 partially deglycosylated enzymes 1420:1451 These proteases contain ∼ 42% to 44% of N-linked carbohydrates by mass whereas partially deglycosylated enzymes showed significantly less catalytic activity as compared to native enzymes. 24520323 1 11 from effects 270:276 arg1 victim 281:286 victim 281:286 victim 281:286 Proteases from Russell's viper venom (RVV) induce a variety of toxic effects in victim. 24520323 5 12 theme BAEE-esterase 894:906 arg1 activities 928:937 significantly different fibrinogenolytic, BAEE-esterase and plasma clotting activities 852:937 activities 928:937 These proteases showed significantly different fibrinogenolytic, BAEE-esterase and plasma clotting activities but no fibrinolytic, TAME-esterase or amidolytic activity against the chromogenic substrate for trypsin, thrombin, plasmin and factor Xa. 24520323 0 13 theme factor 135:140 arg1 activation 144:153 factor V activation 135:153 factor V activation: role of glycosylation on enzymatic activity 135:198 The pro-coagulant fibrinogenolytic serine protease isoenzymes purified from Daboia russelii russelii venom coagulate the blood through factor V activation: role of glycosylation on enzymatic activity. 24520323 3 14 theme significant 523:533 arg1 homology 544:551 significant sequence homology 523:551 significant sequence homology with N-terminal sequences of snake venom thrombin-like and factor V-activating serine proteases, which was reconfirmed by peptide mass fingerprinting analysis 523:710 The first 10 N-terminal residues of these serine protease isoenzymes showed significant sequence homology with N-terminal sequences of snake venom thrombin-like and factor V-activating serine proteases, which was reconfirmed by peptide mass fingerprinting analysis. 24520323 9 15 dep induce 1564:1569 arg1 whereas 1618:1624 whereas 1618:1624 whereas 1618:1624 In vitro these protease isoenzymes induce blood coagulation through factor V activation, whereas in vivo they provoke dose-dependent defibrinogenation and anticoagulant activity in the mouse model. 24520323 1 16 theme viper 226:230 arg1 RVV 239:241 RVV 239:241 RVV 239:241 Proteases from Russell's viper venom (RVV) induce a variety of toxic effects in victim. 24520323 1 16 theme viper 226:230 arg1 venom 232:236 Russell's viper venom 216:236 Russell's viper venom (RVV) 216:242 Proteases from Russell's viper venom (RVV) induce a variety of toxic effects in victim. 24520323 3 17 theme N-terminal 558:567 arg1 sequences 569:577 N-terminal sequences 558:577 N-terminal sequences of snake venom thrombin-like and factor V-activating serine proteases, which was reconfirmed by peptide mass fingerprinting analysis 558:710 The first 10 N-terminal residues of these serine protease isoenzymes showed significant sequence homology with N-terminal sequences of snake venom thrombin-like and factor V-activating serine proteases, which was reconfirmed by peptide mass fingerprinting analysis. 24520323 7 18 dep pattern 1258:1264 arg1 the 1222:1224 the 1222:1224 the 1222:1224 On the basis of fibrinogen degradation pattern, they may be classified as A/B serine proteases isolated from snake venom. 24520323 7 18 dep pattern 1258:1264 arg1 basis 1226:1230 basis 1226:1230 basis 1226:1230 On the basis of fibrinogen degradation pattern, they may be classified as A/B serine proteases isolated from snake venom. 24520323 0 19 theme glycosylation 164:176 arg1 activation 144:153 factor V activation 135:153 factor V activation: role of glycosylation on enzymatic activity 135:198 The pro-coagulant fibrinogenolytic serine protease isoenzymes purified from Daboia russelii russelii venom coagulate the blood through factor V activation: role of glycosylation on enzymatic activity. 24520323 10 20 theme house 1818:1822 arg1 geckos 1824:1829 house geckos 1818:1829 house geckos 1818:1829 At a dose of 5 mg/kg, none of these protease isoenzymes were found to be lethal in mice or house geckos, suggesting therapeutic application of these anticoagulant peptides for the prevention of thrombosis. 24520323 8 21 theme catalytic 1479:1487 arg1 activity 1489:1496 significantly less catalytic activity 1460:1496 significantly less catalytic activity 1460:1496 These proteases contain ∼ 42% to 44% of N-linked carbohydrates by mass whereas partially deglycosylated enzymes showed significantly less catalytic activity as compared to native enzymes. 24520323 7 22 theme serine 1297:1302 arg1 proteases 1304:1312 A/B serine proteases 1293:1312 A/B serine proteases isolated from snake venom 1293:1338 On the basis of fibrinogen degradation pattern, they may be classified as A/B serine proteases isolated from snake venom. 24520323 7 22 theme serine 1297:1302 arg1 they 1267:1270 they 1267:1270 they 1267:1270 On the basis of fibrinogen degradation pattern, they may be classified as A/B serine proteases isolated from snake venom. 24520323 0 23 theme Daboia 76:81 arg1 venom 101:105 Daboia russelii russelii venom 76:105 Daboia russelii russelii venom 76:105 The pro-coagulant fibrinogenolytic serine protease isoenzymes purified from Daboia russelii russelii venom coagulate the blood through factor V activation: role of glycosylation on enzymatic activity. 24520323 3 24 with homology 544:551 arg1 sequences 569:577 N-terminal sequences 558:577 N-terminal sequences of snake venom thrombin-like and factor V-activating serine proteases, which was reconfirmed by peptide mass fingerprinting analysis 558:710 The first 10 N-terminal residues of these serine protease isoenzymes showed significant sequence homology with N-terminal sequences of snake venom thrombin-like and factor V-activating serine proteases, which was reconfirmed by peptide mass fingerprinting analysis. 24520323 5 25 theme plasma 912:917 arg1 activities 928:937 significantly different fibrinogenolytic, BAEE-esterase and plasma clotting activities 852:937 activities 928:937 These proteases showed significantly different fibrinogenolytic, BAEE-esterase and plasma clotting activities but no fibrinolytic, TAME-esterase or amidolytic activity against the chromogenic substrate for trypsin, thrombin, plasmin and factor Xa. 24520323 0 26 theme russelii 92:99 arg1 venom 101:105 Daboia russelii russelii venom 76:105 Daboia russelii russelii venom 76:105 The pro-coagulant fibrinogenolytic serine protease isoenzymes purified from Daboia russelii russelii venom coagulate the blood through factor V activation: role of glycosylation on enzymatic activity. 24520323 9 27 theme protease 1544:1551 arg1 isoenzymes 1553:1562 In vitro these protease isoenzymes 1529:1562 In vitro these protease isoenzymes 1529:1562 In vitro these protease isoenzymes induce blood coagulation through factor V activation, whereas in vivo they provoke dose-dependent defibrinogenation and anticoagulant activity in the mouse model. 24520323 4 28 theme reported 772:779 arg1 activators 790:799 previously reported factor V activators 761:799 previously reported factor V activators isolated from snake venoms 761:826 These proteases were found to be different from previously reported factor V activators isolated from snake venoms. 24520323 1 29 theme toxic 264:268 arg1 effects 270:276 toxic effects 264:276 toxic effects in victim 264:286 Proteases from Russell's viper venom (RVV) induce a variety of toxic effects in victim. 24520323 10 30 theme therapeutic 1843:1853 arg1 application 1855:1865 therapeutic application 1843:1865 therapeutic application of these anticoagulant peptides for the prevention of thrombosis 1843:1930 At a dose of 5 mg/kg, none of these protease isoenzymes were found to be lethal in mice or house geckos, suggesting therapeutic application of these anticoagulant peptides for the prevention of thrombosis. 24520323 8 31 dep % 1376:1376 arg1 to 1371:1372 to 1371:1372 to 1371:1372 These proteases contain ∼ 42% to 44% of N-linked carbohydrates by mass whereas partially deglycosylated enzymes showed significantly less catalytic activity as compared to native enzymes. 24520323 0 32 theme fibrinogenolytic 18:33 arg1 isoenzymes 51:60 The pro-coagulant fibrinogenolytic serine protease isoenzymes 0:60 The pro-coagulant fibrinogenolytic serine protease isoenzymes purified from Daboia russelii russelii venom 0:105 The pro-coagulant fibrinogenolytic serine protease isoenzymes purified from Daboia russelii russelii venom coagulate the blood through factor V activation: role of glycosylation on enzymatic activity. 24520323 9 33 theme factor 1597:1602 arg1 activation 1606:1615 factor V activation 1597:1615 factor V activation 1597:1615 In vitro these protease isoenzymes induce blood coagulation through factor V activation, whereas in vivo they provoke dose-dependent defibrinogenation and anticoagulant activity in the mouse model. 24520323 10 34 from geckos 1824:1829 arg1 lethal 1800:1805 lethal 1800:1805 lethal 1800:1805 At a dose of 5 mg/kg, none of these protease isoenzymes were found to be lethal in mice or house geckos, suggesting therapeutic application of these anticoagulant peptides for the prevention of thrombosis. 24520323 3 35 theme proteases 639:647 arg1 sequences 569:577 N-terminal sequences 558:577 N-terminal sequences of snake venom thrombin-like and factor V-activating serine proteases, which was reconfirmed by peptide mass fingerprinting analysis 558:710 The first 10 N-terminal residues of these serine protease isoenzymes showed significant sequence homology with N-terminal sequences of snake venom thrombin-like and factor V-activating serine proteases, which was reconfirmed by peptide mass fingerprinting analysis. 24520323 4 36 theme snake 815:819 arg1 venoms 821:826 snake venoms 815:826 snake venoms 815:826 These proteases were found to be different from previously reported factor V activators isolated from snake venoms. 24520323 0 37 theme protease 42:49 arg1 isoenzymes 51:60 The pro-coagulant fibrinogenolytic serine protease isoenzymes 0:60 The pro-coagulant fibrinogenolytic serine protease isoenzymes purified from Daboia russelii russelii venom 0:105 The pro-coagulant fibrinogenolytic serine protease isoenzymes purified from Daboia russelii russelii venom coagulate the blood through factor V activation: role of glycosylation on enzymatic activity. 24520323 7 38 theme A/B 1293:1295 arg1 proteases 1304:1312 A/B serine proteases 1293:1312 A/B serine proteases isolated from snake venom 1293:1338 On the basis of fibrinogen degradation pattern, they may be classified as A/B serine proteases isolated from snake venom. 24520323 7 38 theme A/B 1293:1295 arg1 they 1267:1270 they 1267:1270 they 1267:1270 On the basis of fibrinogen degradation pattern, they may be classified as A/B serine proteases isolated from snake venom. 24520323 3 39 theme V-activating 619:630 arg1 proteases 639:647 snake venom thrombin-like and factor V-activating serine proteases 582:647 snake venom thrombin-like and factor V-activating serine proteases 582:647 The first 10 N-terminal residues of these serine protease isoenzymes showed significant sequence homology with N-terminal sequences of snake venom thrombin-like and factor V-activating serine proteases, which was reconfirmed by peptide mass fingerprinting analysis. 24520323 8 40 theme N-linked 1381:1388 arg1 carbohydrates 1390:1402 N-linked carbohydrates 1381:1402 N-linked carbohydrates 1381:1402 These proteases contain ∼ 42% to 44% of N-linked carbohydrates by mass whereas partially deglycosylated enzymes showed significantly less catalytic activity as compared to native enzymes. 24520323 5 41 theme factor 1066:1071 arg1 Xa 1073:1074 factor Xa 1066:1074 factor Xa 1066:1074 These proteases showed significantly different fibrinogenolytic, BAEE-esterase and plasma clotting activities but no fibrinolytic, TAME-esterase or amidolytic activity against the chromogenic substrate for trypsin, thrombin, plasmin and factor Xa. 24520323 10 42 theme anticoagulant 1876:1888 arg1 peptides 1890:1897 these anticoagulant peptides 1870:1897 these anticoagulant peptides 1870:1897 At a dose of 5 mg/kg, none of these protease isoenzymes were found to be lethal in mice or house geckos, suggesting therapeutic application of these anticoagulant peptides for the prevention of thrombosis. 24520323 4 43 theme V 788:788 arg1 activators 790:799 previously reported factor V activators 761:799 previously reported factor V activators isolated from snake venoms 761:826 These proteases were found to be different from previously reported factor V activators isolated from snake venoms. 24520323 2 44 theme RVV 309:311 arg1 isoenzymes 322:331 four new RVV protease isoenzymes 300:331 four new RVV protease isoenzymes of molecular mass 32901.044 Da, 333631.179 Da, 333571.472 Da, and 34594.776 Da, 300:411 Therefore, four new RVV protease isoenzymes of molecular mass 32901.044 Da, 333631.179 Da, 333571.472 Da, and 34594.776 Da, were characterized in this study. 24520323 0 45 dep activation 144:153 arg1 role 156:159 role 156:159 factor V activation: role of glycosylation on enzymatic activity 135:198 The pro-coagulant fibrinogenolytic serine protease isoenzymes purified from Daboia russelii russelii venom coagulate the blood through factor V activation: role of glycosylation on enzymatic activity. 24520323 0 46 from activation 144:153 arg1 activity 191:198 enzymatic activity 181:198 enzymatic activity 181:198 The pro-coagulant fibrinogenolytic serine protease isoenzymes purified from Daboia russelii russelii venom coagulate the blood through factor V activation: role of glycosylation on enzymatic activity. 24520323 7 47 attach isolated 1314:1321 arg2 proteases 1304:1312 A/B serine proteases 1293:1312 A/B serine proteases isolated from snake venom 1293:1338 On the basis of fibrinogen degradation pattern, they may be classified as A/B serine proteases isolated from snake venom. 24520323 7 47 attach isolated 1314:1321 arg2 they 1267:1270 they 1267:1270 they 1267:1270 On the basis of fibrinogen degradation pattern, they may be classified as A/B serine proteases isolated from snake venom. 24520323 7 47 attach isolated 1314:1321 arg1 venom 1334:1338 snake venom 1328:1338 snake venom 1328:1338 On the basis of fibrinogen degradation pattern, they may be classified as A/B serine proteases isolated from snake venom. 24520323 10 48 theme mg/kg 1742:1746 arg1 dose 1732:1735 a dose 1730:1735 a dose of 5 mg/kg 1730:1746 At a dose of 5 mg/kg, none of these protease isoenzymes were found to be lethal in mice or house geckos, suggesting therapeutic application of these anticoagulant peptides for the prevention of thrombosis. 24520323 10 49 located found 1788:1792 arg2 none 1749:1752 none 1749:1752 none of these protease isoenzymes 1749:1781 At a dose of 5 mg/kg, none of these protease isoenzymes were found to be lethal in mice or house geckos, suggesting therapeutic application of these anticoagulant peptides for the prevention of thrombosis. 24520323 10 49 located found 1788:1792 arg1 dose 1732:1735 a dose 1730:1735 a dose of 5 mg/kg 1730:1746 At a dose of 5 mg/kg, none of these protease isoenzymes were found to be lethal in mice or house geckos, suggesting therapeutic application of these anticoagulant peptides for the prevention of thrombosis. 24520323 3 50 theme fingerprinting 688:701 arg1 analysis 703:710 peptide mass fingerprinting analysis 675:710 peptide mass fingerprinting analysis 675:710 The first 10 N-terminal residues of these serine protease isoenzymes showed significant sequence homology with N-terminal sequences of snake venom thrombin-like and factor V-activating serine proteases, which was reconfirmed by peptide mass fingerprinting analysis. 24520323 2 51 theme molecular 336:344 arg1 Da 409:410 34594.776 Da 399:410 34594.776 Da 399:410 Therefore, four new RVV protease isoenzymes of molecular mass 32901.044 Da, 333631.179 Da, 333571.472 Da, and 34594.776 Da, were characterized in this study. 24520323 2 51 theme molecular 336:344 arg1 Da 391:392 333571.472 Da 380:392 333571.472 Da 380:392 Therefore, four new RVV protease isoenzymes of molecular mass 32901.044 Da, 333631.179 Da, 333571.472 Da, and 34594.776 Da, were characterized in this study. 24520323 2 51 theme molecular 336:344 arg1 Da 376:377 333631.179 Da 365:377 333631.179 Da 365:377 Therefore, four new RVV protease isoenzymes of molecular mass 32901.044 Da, 333631.179 Da, 333571.472 Da, and 34594.776 Da, were characterized in this study. 24520323 2 51 theme molecular 336:344 arg1 mass 346:349 molecular mass 32901.044 Da, 333631.179 Da, 333571.472 Da, and 34594.776 Da, 336:411 mass 346:349 Therefore, four new RVV protease isoenzymes of molecular mass 32901.044 Da, 333631.179 Da, 333571.472 Da, and 34594.776 Da, were characterized in this study. 24520323 7 52 theme degradation 1246:1256 arg1 pattern 1258:1264 fibrinogen degradation pattern 1235:1264 fibrinogen degradation pattern 1235:1264 On the basis of fibrinogen degradation pattern, they may be classified as A/B serine proteases isolated from snake venom. 24520323 0 53 from glycosylation 164:176 arg1 activity 191:198 enzymatic activity 181:198 enzymatic activity 181:198 The pro-coagulant fibrinogenolytic serine protease isoenzymes purified from Daboia russelii russelii venom coagulate the blood through factor V activation: role of glycosylation on enzymatic activity. 24520323 3 54 theme peptide 675:681 arg1 fingerprinting 688:701 peptide mass fingerprinting 675:701 peptide mass fingerprinting analysis 675:710 The first 10 N-terminal residues of these serine protease isoenzymes showed significant sequence homology with N-terminal sequences of snake venom thrombin-like and factor V-activating serine proteases, which was reconfirmed by peptide mass fingerprinting analysis. 24520323 5 55 dep different 866:874 arg1 fibrinogenolytic 876:891 fibrinogenolytic 876:891 fibrinogenolytic 876:891 These proteases showed significantly different fibrinogenolytic, BAEE-esterase and plasma clotting activities but no fibrinolytic, TAME-esterase or amidolytic activity against the chromogenic substrate for trypsin, thrombin, plasmin and factor Xa. 24520323 3 56 theme protease 496:503 arg1 isoenzymes 505:514 these serine protease isoenzymes 483:514 these serine protease isoenzymes 483:514 The first 10 N-terminal residues of these serine protease isoenzymes showed significant sequence homology with N-terminal sequences of snake venom thrombin-like and factor V-activating serine proteases, which was reconfirmed by peptide mass fingerprinting analysis. 24520323 9 57 theme anticoagulant 1684:1696 arg1 activity 1698:1705 anticoagulant activity 1684:1705 anticoagulant activity 1684:1705 In vitro these protease isoenzymes induce blood coagulation through factor V activation, whereas in vivo they provoke dose-dependent defibrinogenation and anticoagulant activity in the mouse model. 24520323 5 58 theme clotting 919:926 arg1 activities 928:937 significantly different fibrinogenolytic, BAEE-esterase and plasma clotting activities 852:937 activities 928:937 These proteases showed significantly different fibrinogenolytic, BAEE-esterase and plasma clotting activities but no fibrinolytic, TAME-esterase or amidolytic activity against the chromogenic substrate for trypsin, thrombin, plasmin and factor Xa. 24520323 5 59 theme different 866:874 arg1 activities 928:937 significantly different fibrinogenolytic, BAEE-esterase and plasma clotting activities 852:937 activities 928:937 These proteases showed significantly different fibrinogenolytic, BAEE-esterase and plasma clotting activities but no fibrinolytic, TAME-esterase or amidolytic activity against the chromogenic substrate for trypsin, thrombin, plasmin and factor Xa. 24520323 10 60 theme thrombosis 1921:1930 arg1 prevention 1907:1916 the prevention 1903:1916 the prevention of thrombosis 1903:1930 At a dose of 5 mg/kg, none of these protease isoenzymes were found to be lethal in mice or house geckos, suggesting therapeutic application of these anticoagulant peptides for the prevention of thrombosis. 24520323 3 61 theme sequence 535:542 arg1 homology 544:551 significant sequence homology 523:551 significant sequence homology with N-terminal sequences of snake venom thrombin-like and factor V-activating serine proteases, which was reconfirmed by peptide mass fingerprinting analysis 523:710 The first 10 N-terminal residues of these serine protease isoenzymes showed significant sequence homology with N-terminal sequences of snake venom thrombin-like and factor V-activating serine proteases, which was reconfirmed by peptide mass fingerprinting analysis. 24520323 9 62 theme mouse 1714:1718 arg1 model 1720:1724 the mouse model 1710:1724 the mouse model 1710:1724 In vitro these protease isoenzymes induce blood coagulation through factor V activation, whereas in vivo they provoke dose-dependent defibrinogenation and anticoagulant activity in the mouse model. 24520323 6 63 theme µM 1165:1166 arg1 range 1144:1148 the range 1140:1148 the range of 6.6 to 10.5 µM and 111.0 to 125.5 units/mg protein 1140:1202 Their Km and Vmax values towards fibrinogen were determined in the range of 6.6 to 10.5 µM and 111.0 to 125.5 units/mg protein, respectively. 24520323 0 64 theme V 142:142 arg1 activation 144:153 factor V activation 135:153 factor V activation: role of glycosylation on enzymatic activity 135:198 The pro-coagulant fibrinogenolytic serine protease isoenzymes purified from Daboia russelii russelii venom coagulate the blood through factor V activation: role of glycosylation on enzymatic activity. 24520323 10 65 theme isoenzymes 1772:1781 arg1 none 1749:1752 none 1749:1752 none of these protease isoenzymes 1749:1781 At a dose of 5 mg/kg, none of these protease isoenzymes were found to be lethal in mice or house geckos, suggesting therapeutic application of these anticoagulant peptides for the prevention of thrombosis. 24520323 8 66 theme deglycosylated 1430:1443 arg1 enzymes 1445:1451 partially deglycosylated enzymes 1420:1451 partially deglycosylated enzymes 1420:1451 These proteases contain ∼ 42% to 44% of N-linked carbohydrates by mass whereas partially deglycosylated enzymes showed significantly less catalytic activity as compared to native enzymes. 24520323 2 67 theme protease 313:320 arg1 isoenzymes 322:331 four new RVV protease isoenzymes 300:331 four new RVV protease isoenzymes of molecular mass 32901.044 Da, 333631.179 Da, 333571.472 Da, and 34594.776 Da, 300:411 Therefore, four new RVV protease isoenzymes of molecular mass 32901.044 Da, 333631.179 Da, 333571.472 Da, and 34594.776 Da, were characterized in this study. 24520323 1 68 from variety 253:259 arg1 victim 281:286 victim 281:286 victim 281:286 Proteases from Russell's viper venom (RVV) induce a variety of toxic effects in victim. 24520323 8 69 theme less 1474:1477 arg1 activity 1489:1496 significantly less catalytic activity 1460:1496 significantly less catalytic activity 1460:1496 These proteases contain ∼ 42% to 44% of N-linked carbohydrates by mass whereas partially deglycosylated enzymes showed significantly less catalytic activity as compared to native enzymes. 24520323 6 70 dep protein 1196:1202 arg1 to 1178:1179 to 1178:1179 to 1178:1179 Their Km and Vmax values towards fibrinogen were determined in the range of 6.6 to 10.5 µM and 111.0 to 125.5 units/mg protein, respectively. 24520323 3 71 theme thrombin-like 594:606 arg1 proteases 639:647 snake venom thrombin-like and factor V-activating serine proteases 582:647 snake venom thrombin-like and factor V-activating serine proteases 582:647 The first 10 N-terminal residues of these serine protease isoenzymes showed significant sequence homology with N-terminal sequences of snake venom thrombin-like and factor V-activating serine proteases, which was reconfirmed by peptide mass fingerprinting analysis. 24520323 5 72 theme fibrinolytic 946:957 arg1 activity 988:995 no fibrinolytic, TAME-esterase or amidolytic activity 943:995 no fibrinolytic, TAME-esterase or amidolytic activity against the chromogenic substrate for trypsin, thrombin, plasmin and factor Xa 943:1074 These proteases showed significantly different fibrinogenolytic, BAEE-esterase and plasma clotting activities but no fibrinolytic, TAME-esterase or amidolytic activity against the chromogenic substrate for trypsin, thrombin, plasmin and factor Xa. 24520323 8 73 link N-linked 1381:1388 arg1 carbohydrates 1390:1402 N-linked carbohydrates 1381:1402 N-linked carbohydrates 1381:1402 These proteases contain ∼ 42% to 44% of N-linked carbohydrates by mass whereas partially deglycosylated enzymes showed significantly less catalytic activity as compared to native enzymes. 24520323 0 74 theme russelii 83:90 arg1 venom 101:105 Daboia russelii russelii venom 76:105 Daboia russelii russelii venom 76:105 The pro-coagulant fibrinogenolytic serine protease isoenzymes purified from Daboia russelii russelii venom coagulate the blood through factor V activation: role of glycosylation on enzymatic activity. 24520323 3 75 theme snake 582:586 arg1 venom 588:592 snake venom 582:592 snake venom 582:592 The first 10 N-terminal residues of these serine protease isoenzymes showed significant sequence homology with N-terminal sequences of snake venom thrombin-like and factor V-activating serine proteases, which was reconfirmed by peptide mass fingerprinting analysis. 24520323 4 76 from activators 790:799 arg1 different 746:754 different 746:754 different 746:754 These proteases were found to be different from previously reported factor V activators isolated from snake venoms. 24520323 6 77 theme protein 1196:1202 arg1 range 1144:1148 the range 1140:1148 the range of 6.6 to 10.5 µM and 111.0 to 125.5 units/mg protein 1140:1202 Their Km and Vmax values towards fibrinogen were determined in the range of 6.6 to 10.5 µM and 111.0 to 125.5 units/mg protein, respectively. 24520323 0 78 gly glycosylation 164:176 arg1 activity 191:198 enzymatic activity 181:198 enzymatic activity 181:198 The pro-coagulant fibrinogenolytic serine protease isoenzymes purified from Daboia russelii russelii venom coagulate the blood through factor V activation: role of glycosylation on enzymatic activity. 24520323 8 79 theme native 1513:1518 arg1 enzymes 1520:1526 native enzymes 1513:1526 native enzymes 1513:1526 These proteases contain ∼ 42% to 44% of N-linked carbohydrates by mass whereas partially deglycosylated enzymes showed significantly less catalytic activity as compared to native enzymes. 24520323 4 80 theme factor 781:786 arg1 activators 790:799 previously reported factor V activators 761:799 previously reported factor V activators isolated from snake venoms 761:826 These proteases were found to be different from previously reported factor V activators isolated from snake venoms. 24520323 10 81 theme protease 1763:1770 arg1 isoenzymes 1772:1781 these protease isoenzymes 1757:1781 these protease isoenzymes 1757:1781 At a dose of 5 mg/kg, none of these protease isoenzymes were found to be lethal in mice or house geckos, suggesting therapeutic application of these anticoagulant peptides for the prevention of thrombosis. 24520323 8 82 contain contain 1357:1363 arg1 proteases 1347:1355 These proteases 1341:1355 These proteases 1341:1355 These proteases contain ∼ 42% to 44% of N-linked carbohydrates by mass whereas partially deglycosylated enzymes showed significantly less catalytic activity as compared to native enzymes. 24520323 8 82 contain contain 1357:1363 arg2 carbohydrates 1390:1402 N-linked carbohydrates 1381:1402 N-linked carbohydrates 1381:1402 These proteases contain ∼ 42% to 44% of N-linked carbohydrates by mass whereas partially deglycosylated enzymes showed significantly less catalytic activity as compared to native enzymes. 24520323 8 82 contain contain 1357:1363 arg2 % 1376:1376 ∼ 42% to 44% 1365:1376 ∼ 42% to 44% of N-linked carbohydrates by mass 1365:1410 These proteases contain ∼ 42% to 44% of N-linked carbohydrates by mass whereas partially deglycosylated enzymes showed significantly less catalytic activity as compared to native enzymes. 24520323 4 83 attach isolated 801:808 arg1 venoms 821:826 snake venoms 815:826 snake venoms 815:826 These proteases were found to be different from previously reported factor V activators isolated from snake venoms. 24520323 4 83 attach isolated 801:808 arg2 activators 790:799 previously reported factor V activators 761:799 previously reported factor V activators isolated from snake venoms 761:826 These proteases were found to be different from previously reported factor V activators isolated from snake venoms. 24520323 5 84 theme chromogenic 1009:1019 arg1 substrate 1021:1029 the chromogenic substrate 1005:1029 the chromogenic substrate for trypsin, thrombin, plasmin and factor Xa 1005:1074 These proteases showed significantly different fibrinogenolytic, BAEE-esterase and plasma clotting activities but no fibrinolytic, TAME-esterase or amidolytic activity against the chromogenic substrate for trypsin, thrombin, plasmin and factor Xa. 24520323 7 85 theme snake 1328:1332 arg1 venom 1334:1338 snake venom 1328:1338 snake venom 1328:1338 On the basis of fibrinogen degradation pattern, they may be classified as A/B serine proteases isolated from snake venom. 24520323 2 86 dep mass 346:349 arg1 Da 361:362 32901.044 Da 351:362 32901.044 Da 351:362 Therefore, four new RVV protease isoenzymes of molecular mass 32901.044 Da, 333631.179 Da, 333571.472 Da, and 34594.776 Da, were characterized in this study. 24520323 0 87 theme pro-coagulant 4:16 arg1 isoenzymes 51:60 The pro-coagulant fibrinogenolytic serine protease isoenzymes 0:60 The pro-coagulant fibrinogenolytic serine protease isoenzymes purified from Daboia russelii russelii venom 0:105 The pro-coagulant fibrinogenolytic serine protease isoenzymes purified from Daboia russelii russelii venom coagulate the blood through factor V activation: role of glycosylation on enzymatic activity. 24520323 5 88 theme TAME-esterase 960:972 arg1 activity 988:995 no fibrinolytic, TAME-esterase or amidolytic activity 943:995 no fibrinolytic, TAME-esterase or amidolytic activity against the chromogenic substrate for trypsin, thrombin, plasmin and factor Xa 943:1074 These proteases showed significantly different fibrinogenolytic, BAEE-esterase and plasma clotting activities but no fibrinolytic, TAME-esterase or amidolytic activity against the chromogenic substrate for trypsin, thrombin, plasmin and factor Xa. 24520323 10 89 from lethal 1800:1805 arg1 mice 1810:1813 mice 1810:1813 mice 1810:1813 At a dose of 5 mg/kg, none of these protease isoenzymes were found to be lethal in mice or house geckos, suggesting therapeutic application of these anticoagulant peptides for the prevention of thrombosis. 24520323 10 89 from lethal 1800:1805 arg1 geckos 1824:1829 house geckos 1818:1829 house geckos 1818:1829 At a dose of 5 mg/kg, none of these protease isoenzymes were found to be lethal in mice or house geckos, suggesting therapeutic application of these anticoagulant peptides for the prevention of thrombosis. 24520323 6 90 theme Vmax 1090:1093 arg1 values 1095:1100 Their Km and Vmax values 1077:1100 Their Km and Vmax values towards fibrinogen 1077:1119 Their Km and Vmax values towards fibrinogen were determined in the range of 6.6 to 10.5 µM and 111.0 to 125.5 units/mg protein, respectively. 24520323 8 91 theme ∼ 1365:1365 arg1 % 1376:1376 ∼ 42% to 44% 1365:1376 ∼ 42% to 44% of N-linked carbohydrates by mass 1365:1410 These proteases contain ∼ 42% to 44% of N-linked carbohydrates by mass whereas partially deglycosylated enzymes showed significantly less catalytic activity as compared to native enzymes. 24520323 8 91 theme ∼ 1365:1365 arg1 carbohydrates 1390:1402 N-linked carbohydrates 1381:1402 N-linked carbohydrates 1381:1402 These proteases contain ∼ 42% to 44% of N-linked carbohydrates by mass whereas partially deglycosylated enzymes showed significantly less catalytic activity as compared to native enzymes. 24520323 0 92 theme serine 35:40 arg1 isoenzymes 51:60 The pro-coagulant fibrinogenolytic serine protease isoenzymes 0:60 The pro-coagulant fibrinogenolytic serine protease isoenzymes purified from Daboia russelii russelii venom 0:105 The pro-coagulant fibrinogenolytic serine protease isoenzymes purified from Daboia russelii russelii venom coagulate the blood through factor V activation: role of glycosylation on enzymatic activity. 24520323 1 93 theme effects 270:276 arg1 variety 253:259 a variety 251:259 a variety of toxic effects in victim 251:286 Proteases from Russell's viper venom (RVV) induce a variety of toxic effects in victim. 24520323 1 93 theme effects 270:276 arg1 effects 270:276 toxic effects 264:276 toxic effects in victim 264:286 Proteases from Russell's viper venom (RVV) induce a variety of toxic effects in victim. 24520323 5 94 theme amidolytic 977:986 arg1 activity 988:995 no fibrinolytic, TAME-esterase or amidolytic activity 943:995 no fibrinolytic, TAME-esterase or amidolytic activity against the chromogenic substrate for trypsin, thrombin, plasmin and factor Xa 943:1074 These proteases showed significantly different fibrinogenolytic, BAEE-esterase and plasma clotting activities but no fibrinolytic, TAME-esterase or amidolytic activity against the chromogenic substrate for trypsin, thrombin, plasmin and factor Xa. 24520323 10 95 from mice 1810:1813 arg1 lethal 1800:1805 lethal 1800:1805 lethal 1800:1805 At a dose of 5 mg/kg, none of these protease isoenzymes were found to be lethal in mice or house geckos, suggesting therapeutic application of these anticoagulant peptides for the prevention of thrombosis. 24520323 6 96 theme Km 1083:1084 arg1 values 1095:1100 Their Km and Vmax values 1077:1100 Their Km and Vmax values towards fibrinogen 1077:1119 Their Km and Vmax values towards fibrinogen were determined in the range of 6.6 to 10.5 µM and 111.0 to 125.5 units/mg protein, respectively. 24520323 0 97 from activity 191:198 arg1 activation 144:153 factor V activation 135:153 factor V activation: role of glycosylation on enzymatic activity 135:198 The pro-coagulant fibrinogenolytic serine protease isoenzymes purified from Daboia russelii russelii venom coagulate the blood through factor V activation: role of glycosylation on enzymatic activity. 24520323 3 98 theme serine 632:637 arg1 proteases 639:647 snake venom thrombin-like and factor V-activating serine proteases 582:647 snake venom thrombin-like and factor V-activating serine proteases 582:647 The first 10 N-terminal residues of these serine protease isoenzymes showed significant sequence homology with N-terminal sequences of snake venom thrombin-like and factor V-activating serine proteases, which was reconfirmed by peptide mass fingerprinting analysis. 24520323 8 99 theme % 1369:1369 arg1 % 1376:1376 ∼ 42% to 44% 1365:1376 ∼ 42% to 44% of N-linked carbohydrates by mass 1365:1410 These proteases contain ∼ 42% to 44% of N-linked carbohydrates by mass whereas partially deglycosylated enzymes showed significantly less catalytic activity as compared to native enzymes. 24520323 8 99 theme % 1369:1369 arg1 carbohydrates 1390:1402 N-linked carbohydrates 1381:1402 N-linked carbohydrates 1381:1402 These proteases contain ∼ 42% to 44% of N-linked carbohydrates by mass whereas partially deglycosylated enzymes showed significantly less catalytic activity as compared to native enzymes. 24520323 9 100 theme V 1604:1604 arg1 activation 1606:1615 factor V activation 1597:1615 factor V activation 1597:1615 In vitro these protease isoenzymes induce blood coagulation through factor V activation, whereas in vivo they provoke dose-dependent defibrinogenation and anticoagulant activity in the mouse model. 24520323 10 101 theme peptides 1890:1897 arg1 application 1855:1865 therapeutic application 1843:1865 therapeutic application of these anticoagulant peptides for the prevention of thrombosis 1843:1930 At a dose of 5 mg/kg, none of these protease isoenzymes were found to be lethal in mice or house geckos, suggesting therapeutic application of these anticoagulant peptides for the prevention of thrombosis. 24520323 3 102 theme first 451:455 arg1 isoenzymes 505:514 these serine protease isoenzymes 483:514 these serine protease isoenzymes 483:514 The first 10 N-terminal residues of these serine protease isoenzymes showed significant sequence homology with N-terminal sequences of snake venom thrombin-like and factor V-activating serine proteases, which was reconfirmed by peptide mass fingerprinting analysis. 24520323 3 102 theme first 451:455 arg1 residues 471:478 The first 10 N-terminal residues 447:478 The first 10 N-terminal residues of these serine protease isoenzymes 447:514 The first 10 N-terminal residues of these serine protease isoenzymes showed significant sequence homology with N-terminal sequences of snake venom thrombin-like and factor V-activating serine proteases, which was reconfirmed by peptide mass fingerprinting analysis. 24520323 8 103 theme carbohydrates 1390:1402 arg1 % 1376:1376 ∼ 42% to 44% 1365:1376 ∼ 42% to 44% of N-linked carbohydrates by mass 1365:1410 These proteases contain ∼ 42% to 44% of N-linked carbohydrates by mass whereas partially deglycosylated enzymes showed significantly less catalytic activity as compared to native enzymes. 24520323 8 103 theme carbohydrates 1390:1402 arg1 carbohydrates 1390:1402 N-linked carbohydrates 1381:1402 N-linked carbohydrates 1381:1402 These proteases contain ∼ 42% to 44% of N-linked carbohydrates by mass whereas partially deglycosylated enzymes showed significantly less catalytic activity as compared to native enzymes. 24520323 2 104 theme new 305:307 arg1 isoenzymes 322:331 four new RVV protease isoenzymes 300:331 four new RVV protease isoenzymes of molecular mass 32901.044 Da, 333631.179 Da, 333571.472 Da, and 34594.776 Da, 300:411 Therefore, four new RVV protease isoenzymes of molecular mass 32901.044 Da, 333631.179 Da, 333571.472 Da, and 34594.776 Da, were characterized in this study. 24520323 3 105 theme mass 683:686 arg1 fingerprinting 688:701 peptide mass fingerprinting 675:701 peptide mass fingerprinting analysis 675:710 The first 10 N-terminal residues of these serine protease isoenzymes showed significant sequence homology with N-terminal sequences of snake venom thrombin-like and factor V-activating serine proteases, which was reconfirmed by peptide mass fingerprinting analysis. 24520323 2 106 theme mass 346:349 arg1 isoenzymes 322:331 four new RVV protease isoenzymes 300:331 four new RVV protease isoenzymes of molecular mass 32901.044 Da, 333631.179 Da, 333571.472 Da, and 34594.776 Da, 300:411 Therefore, four new RVV protease isoenzymes of molecular mass 32901.044 Da, 333631.179 Da, 333571.472 Da, and 34594.776 Da, were characterized in this study. 24462641 10 0 from applications 1832:1843 arg1 glycobiology 1848:1859 glycobiology 1848:1859 glycobiology 1848:1859 GENERAL SIGNIFICANCE The novel RPLs reported would find a broad range of applications in glycobiology, diagnostics and in the analysis of biotherapeutics. 24462641 10 0 from applications 1832:1843 arg1 analysis 1885:1892 the analysis 1881:1892 the analysis of biotherapeutics 1881:1911 GENERAL SIGNIFICANCE The novel RPLs reported would find a broad range of applications in glycobiology, diagnostics and in the analysis of biotherapeutics. 24462641 10 0 from applications 1832:1843 arg1 diagnostics 1862:1872 diagnostics 1862:1872 diagnostics 1862:1872 GENERAL SIGNIFICANCE The novel RPLs reported would find a broad range of applications in glycobiology, diagnostics and in the analysis of biotherapeutics. 24462641 6 1 from glycans 1241:1247 arg1 targets 1265:1271 glycoprotein targets 1252:1271 glycoprotein targets 1252:1271 RESULTS This study generated RPLs exhibiting diverse carbohydrate binding activities including specificity and high affinity for β-linked galactose and N-acetyl-lactosamine (LacNAc) displayed by N-linked glycans on glycoprotein targets. 24462641 2 2 theme genetic 427:433 arg1 manipulation 435:446 further genetic manipulation 419:446 further genetic manipulation to create novel recombinant prokaryotic lectins (RPLs) with altered or enhanced carbohydrate binding properties 419:558 Amenability to recombinant expression in Escherichia coli simplifies their production and presents opportunities for further genetic manipulation to create novel recombinant prokaryotic lectins (RPLs) with altered or enhanced carbohydrate binding properties. 24462641 10 3 from glycobiology 1848:1859 arg1 range 1823:1827 a broad range 1815:1827 a broad range of applications in glycobiology, diagnostics and in the analysis of biotherapeutics 1815:1911 GENERAL SIGNIFICANCE The novel RPLs reported would find a broad range of applications in glycobiology, diagnostics and in the analysis of biotherapeutics. 24462641 9 4 theme site-directed 1653:1665 arg1 mutagenesis 1667:1677 site-directed mutagenesis 1653:1677 site-directed mutagenesis 1653:1677 CONCLUSIONS The carbohydrate binding properties of the PA-IL protein can be significantly altered using site-directed mutagenesis strategies to generate novel RPLs with diverse carbohydrate binding properties. 24462641 8 5 theme glycoprotein 1425:1436 arg1 analysis 1438:1445 glycoprotein analysis 1425:1445 glycoprotein analysis 1425:1445 Ultimately, the utility of these novel RPLs for glycoprotein analysis and for selective fractionation and isolation of glycoproteins and their glycoforms was demonstrated. 24462641 7 6 theme amino 1278:1282 arg1 substitutions 1289:1301 Key amino acid substitutions 1274:1301 Key amino acid substitutions 1274:1301 Key amino acid substitutions were identified and linked with specific carbohydrate binding activities. 24462641 4 7 from residues 752:759 arg1 site 789:792 the carbohydrate binding site 764:792 the carbohydrate binding site of a recombinant PA-IL protein 764:823 METHOD Specific amino acid residues in the carbohydrate binding site of a recombinant PA-IL protein were randomly substituted by site-directed mutagenesis. 24462641 4 7 from residues 752:759 arg1 protein 817:823 a recombinant PA-IL protein 797:823 a recombinant PA-IL protein 797:823 METHOD Specific amino acid residues in the carbohydrate binding site of a recombinant PA-IL protein were randomly substituted by site-directed mutagenesis. 24462641 5 8 theme carbohydrate 1004:1015 arg1 properties 1025:1034 altered carbohydrate binding properties 996:1034 altered carbohydrate binding properties 996:1034 The resulting expression clones were then functionally screened to identify clones expressing rPA-IL proteins with altered carbohydrate binding properties. 24462641 4 9 theme METHOD 725:730 arg1 residues 752:759 METHOD Specific amino acid residues 725:759 METHOD Specific amino acid residues in the carbohydrate binding site of a recombinant PA-IL protein 725:823 METHOD Specific amino acid residues in the carbohydrate binding site of a recombinant PA-IL protein were randomly substituted by site-directed mutagenesis. 24462641 10 10 theme applications 1832:1843 arg1 range 1823:1827 a broad range 1815:1827 a broad range of applications in glycobiology, diagnostics and in the analysis of biotherapeutics 1815:1911 GENERAL SIGNIFICANCE The novel RPLs reported would find a broad range of applications in glycobiology, diagnostics and in the analysis of biotherapeutics. 24462641 4 11 theme amino 741:745 arg1 residues 752:759 METHOD Specific amino acid residues 725:759 METHOD Specific amino acid residues in the carbohydrate binding site of a recombinant PA-IL protein 725:823 METHOD Specific amino acid residues in the carbohydrate binding site of a recombinant PA-IL protein were randomly substituted by site-directed mutagenesis. 24462641 7 12 theme carbohydrate 1344:1355 arg1 activities 1365:1374 specific carbohydrate binding activities 1335:1374 specific carbohydrate binding activities 1335:1374 Key amino acid substitutions were identified and linked with specific carbohydrate binding activities. 24462641 8 13 theme glycoproteins 1496:1508 arg1 isolation 1483:1491 isolation 1483:1491 isolation 1483:1491 Ultimately, the utility of these novel RPLs for glycoprotein analysis and for selective fractionation and isolation of glycoproteins and their glycoforms was demonstrated. 24462641 8 13 theme glycoproteins 1496:1508 arg1 fractionation 1465:1477 selective fractionation 1455:1477 selective fractionation 1455:1477 Ultimately, the utility of these novel RPLs for glycoprotein analysis and for selective fractionation and isolation of glycoproteins and their glycoforms was demonstrated. 24462641 8 14 theme RPLs 1416:1419 arg1 utility 1393:1399 the utility 1389:1399 the utility of these novel RPLs for glycoprotein analysis and for selective fractionation and isolation of glycoproteins and their glycoforms 1389:1529 Ultimately, the utility of these novel RPLs for glycoprotein analysis and for selective fractionation and isolation of glycoproteins and their glycoforms was demonstrated. 24462641 6 15 theme carbohydrate 1090:1101 arg1 specificity 1132:1142 specificity 1132:1142 specificity 1132:1142 RESULTS This study generated RPLs exhibiting diverse carbohydrate binding activities including specificity and high affinity for β-linked galactose and N-acetyl-lactosamine (LacNAc) displayed by N-linked glycans on glycoprotein targets. 24462641 6 15 theme carbohydrate 1090:1101 arg1 affinity 1153:1160 high affinity 1148:1160 high affinity 1148:1160 RESULTS This study generated RPLs exhibiting diverse carbohydrate binding activities including specificity and high affinity for β-linked galactose and N-acetyl-lactosamine (LacNAc) displayed by N-linked glycans on glycoprotein targets. 24462641 6 15 theme carbohydrate 1090:1101 arg1 activities 1111:1120 diverse carbohydrate binding activities 1082:1120 diverse carbohydrate binding activities including specificity and high affinity for β-linked galactose and N-acetyl-lactosamine (LacNAc) displayed by N-linked glycans on glycoprotein targets 1082:1271 RESULTS This study generated RPLs exhibiting diverse carbohydrate binding activities including specificity and high affinity for β-linked galactose and N-acetyl-lactosamine (LacNAc) displayed by N-linked glycans on glycoprotein targets. 24462641 4 16 theme recombinant 799:809 arg1 protein 817:823 a recombinant PA-IL protein 797:823 a recombinant PA-IL protein 797:823 METHOD Specific amino acid residues in the carbohydrate binding site of a recombinant PA-IL protein were randomly substituted by site-directed mutagenesis. 24462641 9 17 theme binding 1739:1745 arg1 properties 1747:1756 diverse carbohydrate binding properties 1718:1756 diverse carbohydrate binding properties 1718:1756 CONCLUSIONS The carbohydrate binding properties of the PA-IL protein can be significantly altered using site-directed mutagenesis strategies to generate novel RPLs with diverse carbohydrate binding properties. 24462641 2 18 theme recombinant 317:327 arg1 expression 329:338 recombinant expression 317:338 recombinant expression in Escherichia coli 317:358 Amenability to recombinant expression in Escherichia coli simplifies their production and presents opportunities for further genetic manipulation to create novel recombinant prokaryotic lectins (RPLs) with altered or enhanced carbohydrate binding properties. 24462641 4 19 theme protein 817:823 arg1 site 789:792 the carbohydrate binding site 764:792 the carbohydrate binding site of a recombinant PA-IL protein 764:823 METHOD Specific amino acid residues in the carbohydrate binding site of a recombinant PA-IL protein were randomly substituted by site-directed mutagenesis. 24462641 4 19 theme protein 817:823 arg1 protein 817:823 a recombinant PA-IL protein 797:823 a recombinant PA-IL protein 797:823 METHOD Specific amino acid residues in the carbohydrate binding site of a recombinant PA-IL protein were randomly substituted by site-directed mutagenesis. 24462641 3 20 theme RPLs 719:722 arg1 generation 699:708 the generation 695:708 the generation of novel RPLs 695:722 This study explored the potential of the α-galactophilic PA-IL lectin from Pseudomonas aeruginosa for use as a scaffold structure for the generation of novel RPLs. 24462641 9 21 theme diverse 1718:1724 arg1 properties 1747:1756 diverse carbohydrate binding properties 1718:1756 diverse carbohydrate binding properties 1718:1756 CONCLUSIONS The carbohydrate binding properties of the PA-IL protein can be significantly altered using site-directed mutagenesis strategies to generate novel RPLs with diverse carbohydrate binding properties. 24462641 8 22 theme glycoforms 1520:1529 arg1 isolation 1483:1491 isolation 1483:1491 isolation 1483:1491 Ultimately, the utility of these novel RPLs for glycoprotein analysis and for selective fractionation and isolation of glycoproteins and their glycoforms was demonstrated. 24462641 8 22 theme glycoforms 1520:1529 arg1 fractionation 1465:1477 selective fractionation 1455:1477 selective fractionation 1455:1477 Ultimately, the utility of these novel RPLs for glycoprotein analysis and for selective fractionation and isolation of glycoproteins and their glycoforms was demonstrated. 24462641 0 23 theme binding 75:81 arg1 properties 83:92 altered carbohydrate binding properties 54:92 altered carbohydrate binding properties 54:92 Generating novel recombinant prokaryotic lectins with altered carbohydrate binding properties through mutagenesis of the PA-IL protein from Pseudomonas aeruginosa. 24462641 0 24 theme recombinant 17:27 arg1 lectins 41:47 novel recombinant prokaryotic lectins 11:47 novel recombinant prokaryotic lectins with altered carbohydrate binding properties 11:92 Generating novel recombinant prokaryotic lectins with altered carbohydrate binding properties through mutagenesis of the PA-IL protein from Pseudomonas aeruginosa. 24462641 1 25 theme Prokaryotic 175:185 arg1 lectins 187:193 BACKGROUND Prokaryotic lectins 164:193 BACKGROUND Prokaryotic lectins 164:193 BACKGROUND Prokaryotic lectins offer significant advantages over eukaryotic lectins for the development of enhanced glycoselective tools. 24462641 8 26 gly glycoproteins 1496:1508 arg1 glycoproteins 1496:1508 glycoproteins 1496:1508 glycoproteins 1496:1508 Ultimately, the utility of these novel RPLs for glycoprotein analysis and for selective fractionation and isolation of glycoproteins and their glycoforms was demonstrated. 24462641 9 27 dep CONCLUSIONS 1549:1559 arg1 altered 1639:1645 altered 1639:1645 can be significantly altered using site-directed mutagenesis strategies to generate novel RPLs with diverse carbohydrate binding properties 1618:1756 CONCLUSIONS The carbohydrate binding properties of the PA-IL protein can be significantly altered using site-directed mutagenesis strategies to generate novel RPLs with diverse carbohydrate binding properties. 24462641 11 28 gly glycoprotein 2031:2042 arg1 glycoprotein 2031:2042 glycoprotein 2031:2042 glycoprotein 2031:2042 The ability to readily produce these RPLs in gram quantities could enable them to find larger scale applications for glycoprotein or biotherapeutic purification. 24462641 3 29 from aeruginosa 648:657 arg1 lectin 624:629 the α-galactophilic PA-IL lectin 598:629 the α-galactophilic PA-IL lectin from Pseudomonas aeruginosa 598:657 This study explored the potential of the α-galactophilic PA-IL lectin from Pseudomonas aeruginosa for use as a scaffold structure for the generation of novel RPLs. 24462641 3 29 from aeruginosa 648:657 arg1 potential 585:593 the potential 581:593 the potential of the α-galactophilic PA-IL lectin from Pseudomonas aeruginosa for use as a scaffold structure for the generation of novel RPLs 581:722 This study explored the potential of the α-galactophilic PA-IL lectin from Pseudomonas aeruginosa for use as a scaffold structure for the generation of novel RPLs. 24462641 11 30 theme scale 2008:2012 arg1 applications 2014:2025 larger scale applications 2001:2025 larger scale applications for glycoprotein or biotherapeutic purification 2001:2073 The ability to readily produce these RPLs in gram quantities could enable them to find larger scale applications for glycoprotein or biotherapeutic purification. 24462641 6 31 theme high 1148:1151 arg1 affinity 1153:1160 high affinity 1148:1160 high affinity 1148:1160 RESULTS This study generated RPLs exhibiting diverse carbohydrate binding activities including specificity and high affinity for β-linked galactose and N-acetyl-lactosamine (LacNAc) displayed by N-linked glycans on glycoprotein targets. 24462641 0 32 theme PA-IL 121:125 arg1 protein 127:133 the PA-IL protein 117:133 the PA-IL protein from Pseudomonas aeruginosa 117:161 Generating novel recombinant prokaryotic lectins with altered carbohydrate binding properties through mutagenesis of the PA-IL protein from Pseudomonas aeruginosa. 24462641 2 33 theme carbohydrate 528:539 arg1 properties 549:558 altered or enhanced carbohydrate binding properties 508:558 altered or enhanced carbohydrate binding properties 508:558 Amenability to recombinant expression in Escherichia coli simplifies their production and presents opportunities for further genetic manipulation to create novel recombinant prokaryotic lectins (RPLs) with altered or enhanced carbohydrate binding properties. 24462641 2 34 theme recombinant 464:474 arg1 RPLs 497:500 RPLs 497:500 RPLs 497:500 Amenability to recombinant expression in Escherichia coli simplifies their production and presents opportunities for further genetic manipulation to create novel recombinant prokaryotic lectins (RPLs) with altered or enhanced carbohydrate binding properties. 24462641 2 34 theme recombinant 464:474 arg1 lectins 488:494 novel recombinant prokaryotic lectins 458:494 novel recombinant prokaryotic lectins (RPLs) with altered or enhanced carbohydrate binding properties 458:558 Amenability to recombinant expression in Escherichia coli simplifies their production and presents opportunities for further genetic manipulation to create novel recombinant prokaryotic lectins (RPLs) with altered or enhanced carbohydrate binding properties. 24462641 6 35 theme N-linked 1232:1239 arg1 glycans 1241:1247 N-linked glycans 1232:1247 N-linked glycans on glycoprotein targets 1232:1271 RESULTS This study generated RPLs exhibiting diverse carbohydrate binding activities including specificity and high affinity for β-linked galactose and N-acetyl-lactosamine (LacNAc) displayed by N-linked glycans on glycoprotein targets. 24462641 7 36 theme binding 1357:1363 arg1 activities 1365:1374 specific carbohydrate binding activities 1335:1374 specific carbohydrate binding activities 1335:1374 Key amino acid substitutions were identified and linked with specific carbohydrate binding activities. 24462641 4 37 theme binding 781:787 arg1 site 789:792 the carbohydrate binding site 764:792 the carbohydrate binding site of a recombinant PA-IL protein 764:823 METHOD Specific amino acid residues in the carbohydrate binding site of a recombinant PA-IL protein were randomly substituted by site-directed mutagenesis. 24462641 4 37 theme binding 781:787 arg1 protein 817:823 a recombinant PA-IL protein 797:823 a recombinant PA-IL protein 797:823 METHOD Specific amino acid residues in the carbohydrate binding site of a recombinant PA-IL protein were randomly substituted by site-directed mutagenesis. 24462641 7 38 theme specific 1335:1342 arg1 activities 1365:1374 specific carbohydrate binding activities 1335:1374 specific carbohydrate binding activities 1335:1374 Key amino acid substitutions were identified and linked with specific carbohydrate binding activities. 24462641 9 39 theme binding 1578:1584 arg1 properties 1586:1595 The carbohydrate binding properties 1561:1595 The carbohydrate binding properties of the PA-IL protein 1561:1616 CONCLUSIONS The carbohydrate binding properties of the PA-IL protein can be significantly altered using site-directed mutagenesis strategies to generate novel RPLs with diverse carbohydrate binding properties. 24462641 5 40 theme expression 895:904 arg1 clones 906:911 The resulting expression clones 881:911 The resulting expression clones 881:911 The resulting expression clones were then functionally screened to identify clones expressing rPA-IL proteins with altered carbohydrate binding properties. 24462641 10 41 theme novel 1784:1788 arg1 RPLs 1790:1793 The novel RPLs 1780:1793 GENERAL SIGNIFICANCE The novel RPLs reported 1759:1802 GENERAL SIGNIFICANCE The novel RPLs reported would find a broad range of applications in glycobiology, diagnostics and in the analysis of biotherapeutics. 24462641 2 42 theme further 419:425 arg1 manipulation 435:446 further genetic manipulation 419:446 further genetic manipulation to create novel recombinant prokaryotic lectins (RPLs) with altered or enhanced carbohydrate binding properties 419:558 Amenability to recombinant expression in Escherichia coli simplifies their production and presents opportunities for further genetic manipulation to create novel recombinant prokaryotic lectins (RPLs) with altered or enhanced carbohydrate binding properties. 24462641 0 43 theme altered 54:60 arg1 properties 83:92 altered carbohydrate binding properties 54:92 altered carbohydrate binding properties 54:92 Generating novel recombinant prokaryotic lectins with altered carbohydrate binding properties through mutagenesis of the PA-IL protein from Pseudomonas aeruginosa. 24462641 9 44 theme PA-IL 1604:1608 arg1 protein 1610:1616 the PA-IL protein 1600:1616 the PA-IL protein 1600:1616 CONCLUSIONS The carbohydrate binding properties of the PA-IL protein can be significantly altered using site-directed mutagenesis strategies to generate novel RPLs with diverse carbohydrate binding properties. 24462641 0 45 from aeruginosa 152:161 arg1 mutagenesis 102:112 mutagenesis 102:112 mutagenesis of the PA-IL protein from Pseudomonas aeruginosa 102:161 Generating novel recombinant prokaryotic lectins with altered carbohydrate binding properties through mutagenesis of the PA-IL protein from Pseudomonas aeruginosa. 24462641 0 45 from aeruginosa 152:161 arg1 protein 127:133 the PA-IL protein 117:133 the PA-IL protein from Pseudomonas aeruginosa 117:161 Generating novel recombinant prokaryotic lectins with altered carbohydrate binding properties through mutagenesis of the PA-IL protein from Pseudomonas aeruginosa. 24462641 3 46 theme α-galactophilic 602:616 arg1 lectin 624:629 the α-galactophilic PA-IL lectin 598:629 the α-galactophilic PA-IL lectin from Pseudomonas aeruginosa 598:657 This study explored the potential of the α-galactophilic PA-IL lectin from Pseudomonas aeruginosa for use as a scaffold structure for the generation of novel RPLs. 24462641 1 47 theme glycoselective 280:293 arg1 tools 295:299 enhanced glycoselective tools 271:299 enhanced glycoselective tools 271:299 BACKGROUND Prokaryotic lectins offer significant advantages over eukaryotic lectins for the development of enhanced glycoselective tools. 24462641 6 48 link N-linked 1232:1239 arg1 glycans 1241:1247 N-linked glycans 1232:1247 N-linked glycans on glycoprotein targets 1232:1271 RESULTS This study generated RPLs exhibiting diverse carbohydrate binding activities including specificity and high affinity for β-linked galactose and N-acetyl-lactosamine (LacNAc) displayed by N-linked glycans on glycoprotein targets. 24462641 0 49 with lectins 41:47 arg1 properties 83:92 altered carbohydrate binding properties 54:92 altered carbohydrate binding properties 54:92 Generating novel recombinant prokaryotic lectins with altered carbohydrate binding properties through mutagenesis of the PA-IL protein from Pseudomonas aeruginosa. 24462641 2 50 with lectins 488:494 arg1 properties 549:558 altered or enhanced carbohydrate binding properties 508:558 altered or enhanced carbohydrate binding properties 508:558 Amenability to recombinant expression in Escherichia coli simplifies their production and presents opportunities for further genetic manipulation to create novel recombinant prokaryotic lectins (RPLs) with altered or enhanced carbohydrate binding properties. 24462641 7 51 theme acid 1284:1287 arg1 substitutions 1289:1301 Key amino acid substitutions 1274:1301 Key amino acid substitutions 1274:1301 Key amino acid substitutions were identified and linked with specific carbohydrate binding activities. 24462641 10 52 theme broad 1817:1821 arg1 range 1823:1827 a broad range 1815:1827 a broad range of applications in glycobiology, diagnostics and in the analysis of biotherapeutics 1815:1911 GENERAL SIGNIFICANCE The novel RPLs reported would find a broad range of applications in glycobiology, diagnostics and in the analysis of biotherapeutics. 24462641 7 53 theme Key 1274:1276 arg1 substitutions 1289:1301 Key amino acid substitutions 1274:1301 Key amino acid substitutions 1274:1301 Key amino acid substitutions were identified and linked with specific carbohydrate binding activities. 24462641 3 54 theme lectin 624:629 arg1 potential 585:593 the potential 581:593 the potential of the α-galactophilic PA-IL lectin from Pseudomonas aeruginosa for use as a scaffold structure for the generation of novel RPLs 581:722 This study explored the potential of the α-galactophilic PA-IL lectin from Pseudomonas aeruginosa for use as a scaffold structure for the generation of novel RPLs. 24462641 1 55 theme significant 201:211 arg1 advantages 213:222 significant advantages 201:222 significant advantages over eukaryotic lectins for the development of enhanced glycoselective tools 201:299 BACKGROUND Prokaryotic lectins offer significant advantages over eukaryotic lectins for the development of enhanced glycoselective tools. 24462641 4 56 theme acid 747:750 arg1 residues 752:759 METHOD Specific amino acid residues 725:759 METHOD Specific amino acid residues in the carbohydrate binding site of a recombinant PA-IL protein 725:823 METHOD Specific amino acid residues in the carbohydrate binding site of a recombinant PA-IL protein were randomly substituted by site-directed mutagenesis. 24462641 5 57 theme altered 996:1002 arg1 properties 1025:1034 altered carbohydrate binding properties 996:1034 altered carbohydrate binding properties 996:1034 The resulting expression clones were then functionally screened to identify clones expressing rPA-IL proteins with altered carbohydrate binding properties. 24462641 3 58 from potential 585:593 arg1 aeruginosa 648:657 Pseudomonas aeruginosa 636:657 Pseudomonas aeruginosa 636:657 This study explored the potential of the α-galactophilic PA-IL lectin from Pseudomonas aeruginosa for use as a scaffold structure for the generation of novel RPLs. 24462641 6 59 link β-linked 1166:1173 arg1 galactose 1175:1183 β-linked galactose 1166:1183 β-linked galactose 1166:1183 RESULTS This study generated RPLs exhibiting diverse carbohydrate binding activities including specificity and high affinity for β-linked galactose and N-acetyl-lactosamine (LacNAc) displayed by N-linked glycans on glycoprotein targets. 24462641 9 60 theme novel 1702:1706 arg1 RPLs 1708:1711 novel RPLs 1702:1711 novel RPLs with diverse carbohydrate binding properties 1702:1756 CONCLUSIONS The carbohydrate binding properties of the PA-IL protein can be significantly altered using site-directed mutagenesis strategies to generate novel RPLs with diverse carbohydrate binding properties. 24462641 0 61 from mutagenesis 102:112 arg1 aeruginosa 152:161 Pseudomonas aeruginosa 140:161 Pseudomonas aeruginosa 140:161 Generating novel recombinant prokaryotic lectins with altered carbohydrate binding properties through mutagenesis of the PA-IL protein from Pseudomonas aeruginosa. 24462641 1 62 theme BACKGROUND 164:173 arg1 lectins 187:193 BACKGROUND Prokaryotic lectins 164:193 BACKGROUND Prokaryotic lectins 164:193 BACKGROUND Prokaryotic lectins offer significant advantages over eukaryotic lectins for the development of enhanced glycoselective tools. 24462641 11 63 theme biotherapeutic 2047:2060 arg1 purification 2062:2073 biotherapeutic purification 2047:2073 biotherapeutic purification 2047:2073 The ability to readily produce these RPLs in gram quantities could enable them to find larger scale applications for glycoprotein or biotherapeutic purification. 24462641 8 64 gly glycoprotein 1425:1436 arg1 glycoprotein 1425:1436 glycoprotein analysis 1425:1445 glycoprotein analysis 1425:1445 Ultimately, the utility of these novel RPLs for glycoprotein analysis and for selective fractionation and isolation of glycoproteins and their glycoforms was demonstrated. 24462641 1 65 theme eukaryotic 229:238 arg1 lectins 240:246 eukaryotic lectins 229:246 eukaryotic lectins 229:246 BACKGROUND Prokaryotic lectins offer significant advantages over eukaryotic lectins for the development of enhanced glycoselective tools. 24462641 6 66 theme binding 1103:1109 arg1 specificity 1132:1142 specificity 1132:1142 specificity 1132:1142 RESULTS This study generated RPLs exhibiting diverse carbohydrate binding activities including specificity and high affinity for β-linked galactose and N-acetyl-lactosamine (LacNAc) displayed by N-linked glycans on glycoprotein targets. 24462641 6 66 theme binding 1103:1109 arg1 affinity 1153:1160 high affinity 1148:1160 high affinity 1148:1160 RESULTS This study generated RPLs exhibiting diverse carbohydrate binding activities including specificity and high affinity for β-linked galactose and N-acetyl-lactosamine (LacNAc) displayed by N-linked glycans on glycoprotein targets. 24462641 6 66 theme binding 1103:1109 arg1 activities 1111:1120 diverse carbohydrate binding activities 1082:1120 diverse carbohydrate binding activities including specificity and high affinity for β-linked galactose and N-acetyl-lactosamine (LacNAc) displayed by N-linked glycans on glycoprotein targets 1082:1271 RESULTS This study generated RPLs exhibiting diverse carbohydrate binding activities including specificity and high affinity for β-linked galactose and N-acetyl-lactosamine (LacNAc) displayed by N-linked glycans on glycoprotein targets. 24462641 4 67 theme Specific 732:739 arg1 residues 752:759 METHOD Specific amino acid residues 725:759 METHOD Specific amino acid residues in the carbohydrate binding site of a recombinant PA-IL protein 725:823 METHOD Specific amino acid residues in the carbohydrate binding site of a recombinant PA-IL protein were randomly substituted by site-directed mutagenesis. 24462641 3 68 theme scaffold 672:679 arg1 structure 681:689 a scaffold structure 670:689 a scaffold structure for the generation of novel RPLs 670:722 This study explored the potential of the α-galactophilic PA-IL lectin from Pseudomonas aeruginosa for use as a scaffold structure for the generation of novel RPLs. 24462641 9 69 theme carbohydrate 1726:1737 arg1 properties 1747:1756 diverse carbohydrate binding properties 1718:1756 diverse carbohydrate binding properties 1718:1756 CONCLUSIONS The carbohydrate binding properties of the PA-IL protein can be significantly altered using site-directed mutagenesis strategies to generate novel RPLs with diverse carbohydrate binding properties. 24462641 8 70 theme novel 1410:1414 arg1 RPLs 1416:1419 these novel RPLs 1404:1419 these novel RPLs 1404:1419 Ultimately, the utility of these novel RPLs for glycoprotein analysis and for selective fractionation and isolation of glycoproteins and their glycoforms was demonstrated. 24462641 6 71 theme diverse 1082:1088 arg1 specificity 1132:1142 specificity 1132:1142 specificity 1132:1142 RESULTS This study generated RPLs exhibiting diverse carbohydrate binding activities including specificity and high affinity for β-linked galactose and N-acetyl-lactosamine (LacNAc) displayed by N-linked glycans on glycoprotein targets. 24462641 6 71 theme diverse 1082:1088 arg1 affinity 1153:1160 high affinity 1148:1160 high affinity 1148:1160 RESULTS This study generated RPLs exhibiting diverse carbohydrate binding activities including specificity and high affinity for β-linked galactose and N-acetyl-lactosamine (LacNAc) displayed by N-linked glycans on glycoprotein targets. 24462641 6 71 theme diverse 1082:1088 arg1 activities 1111:1120 diverse carbohydrate binding activities 1082:1120 diverse carbohydrate binding activities including specificity and high affinity for β-linked galactose and N-acetyl-lactosamine (LacNAc) displayed by N-linked glycans on glycoprotein targets 1082:1271 RESULTS This study generated RPLs exhibiting diverse carbohydrate binding activities including specificity and high affinity for β-linked galactose and N-acetyl-lactosamine (LacNAc) displayed by N-linked glycans on glycoprotein targets. 24462641 3 72 theme novel 713:717 arg1 RPLs 719:722 novel RPLs 713:722 novel RPLs 713:722 This study explored the potential of the α-galactophilic PA-IL lectin from Pseudomonas aeruginosa for use as a scaffold structure for the generation of novel RPLs. 24462641 2 73 from expression 329:338 arg1 coli 355:358 Escherichia coli 343:358 Escherichia coli 343:358 Amenability to recombinant expression in Escherichia coli simplifies their production and presents opportunities for further genetic manipulation to create novel recombinant prokaryotic lectins (RPLs) with altered or enhanced carbohydrate binding properties. 24462641 4 74 theme PA-IL 811:815 arg1 protein 817:823 a recombinant PA-IL protein 797:823 a recombinant PA-IL protein 797:823 METHOD Specific amino acid residues in the carbohydrate binding site of a recombinant PA-IL protein were randomly substituted by site-directed mutagenesis. 24462641 11 75 theme larger 2001:2006 arg1 applications 2014:2025 larger scale applications 2001:2025 larger scale applications for glycoprotein or biotherapeutic purification 2001:2073 The ability to readily produce these RPLs in gram quantities could enable them to find larger scale applications for glycoprotein or biotherapeutic purification. 24462641 10 76 dep SIGNIFICANCE 1767:1778 arg1 RPLs 1790:1793 The novel RPLs 1780:1793 GENERAL SIGNIFICANCE The novel RPLs reported 1759:1802 GENERAL SIGNIFICANCE The novel RPLs reported would find a broad range of applications in glycobiology, diagnostics and in the analysis of biotherapeutics. 24462641 8 77 theme selective 1455:1463 arg1 fractionation 1465:1477 selective fractionation 1455:1477 selective fractionation 1455:1477 Ultimately, the utility of these novel RPLs for glycoprotein analysis and for selective fractionation and isolation of glycoproteins and their glycoforms was demonstrated. 24462641 5 78 theme binding 1017:1023 arg1 properties 1025:1034 altered carbohydrate binding properties 996:1034 altered carbohydrate binding properties 996:1034 The resulting expression clones were then functionally screened to identify clones expressing rPA-IL proteins with altered carbohydrate binding properties. 24462641 4 79 theme carbohydrate 768:779 arg1 site 789:792 the carbohydrate binding site 764:792 the carbohydrate binding site of a recombinant PA-IL protein 764:823 METHOD Specific amino acid residues in the carbohydrate binding site of a recombinant PA-IL protein were randomly substituted by site-directed mutagenesis. 24462641 4 79 theme carbohydrate 768:779 arg1 protein 817:823 a recombinant PA-IL protein 797:823 a recombinant PA-IL protein 797:823 METHOD Specific amino acid residues in the carbohydrate binding site of a recombinant PA-IL protein were randomly substituted by site-directed mutagenesis. 24462641 6 80 theme β-linked 1166:1173 arg1 galactose 1175:1183 β-linked galactose 1166:1183 β-linked galactose 1166:1183 RESULTS This study generated RPLs exhibiting diverse carbohydrate binding activities including specificity and high affinity for β-linked galactose and N-acetyl-lactosamine (LacNAc) displayed by N-linked glycans on glycoprotein targets. 24462641 4 81 theme site-directed 854:866 arg1 mutagenesis 868:878 site-directed mutagenesis 854:878 site-directed mutagenesis 854:878 METHOD Specific amino acid residues in the carbohydrate binding site of a recombinant PA-IL protein were randomly substituted by site-directed mutagenesis. 24462641 0 82 theme protein 127:133 arg1 mutagenesis 102:112 mutagenesis 102:112 mutagenesis of the PA-IL protein from Pseudomonas aeruginosa 102:161 Generating novel recombinant prokaryotic lectins with altered carbohydrate binding properties through mutagenesis of the PA-IL protein from Pseudomonas aeruginosa. 24462641 6 83 theme glycoprotein 1252:1263 arg1 targets 1265:1271 glycoprotein targets 1252:1271 glycoprotein targets 1252:1271 RESULTS This study generated RPLs exhibiting diverse carbohydrate binding activities including specificity and high affinity for β-linked galactose and N-acetyl-lactosamine (LacNAc) displayed by N-linked glycans on glycoprotein targets. 24462641 1 84 theme enhanced 271:278 arg1 tools 295:299 enhanced glycoselective tools 271:299 enhanced glycoselective tools 271:299 BACKGROUND Prokaryotic lectins offer significant advantages over eukaryotic lectins for the development of enhanced glycoselective tools. 24462641 2 85 theme prokaryotic 476:486 arg1 RPLs 497:500 RPLs 497:500 RPLs 497:500 Amenability to recombinant expression in Escherichia coli simplifies their production and presents opportunities for further genetic manipulation to create novel recombinant prokaryotic lectins (RPLs) with altered or enhanced carbohydrate binding properties. 24462641 2 85 theme prokaryotic 476:486 arg1 lectins 488:494 novel recombinant prokaryotic lectins 458:494 novel recombinant prokaryotic lectins (RPLs) with altered or enhanced carbohydrate binding properties 458:558 Amenability to recombinant expression in Escherichia coli simplifies their production and presents opportunities for further genetic manipulation to create novel recombinant prokaryotic lectins (RPLs) with altered or enhanced carbohydrate binding properties. 24462641 0 86 theme novel 11:15 arg1 lectins 41:47 novel recombinant prokaryotic lectins 11:47 novel recombinant prokaryotic lectins with altered carbohydrate binding properties 11:92 Generating novel recombinant prokaryotic lectins with altered carbohydrate binding properties through mutagenesis of the PA-IL protein from Pseudomonas aeruginosa. 24462641 2 87 theme enhanced 519:526 arg1 properties 549:558 altered or enhanced carbohydrate binding properties 508:558 altered or enhanced carbohydrate binding properties 508:558 Amenability to recombinant expression in Escherichia coli simplifies their production and presents opportunities for further genetic manipulation to create novel recombinant prokaryotic lectins (RPLs) with altered or enhanced carbohydrate binding properties. 24462641 10 88 from range 1823:1827 arg1 glycobiology 1848:1859 glycobiology 1848:1859 glycobiology 1848:1859 GENERAL SIGNIFICANCE The novel RPLs reported would find a broad range of applications in glycobiology, diagnostics and in the analysis of biotherapeutics. 24462641 10 88 from range 1823:1827 arg1 analysis 1885:1892 the analysis 1881:1892 the analysis of biotherapeutics 1881:1911 GENERAL SIGNIFICANCE The novel RPLs reported would find a broad range of applications in glycobiology, diagnostics and in the analysis of biotherapeutics. 24462641 10 88 from range 1823:1827 arg1 diagnostics 1862:1872 diagnostics 1862:1872 diagnostics 1862:1872 GENERAL SIGNIFICANCE The novel RPLs reported would find a broad range of applications in glycobiology, diagnostics and in the analysis of biotherapeutics. 24462641 2 89 theme novel 458:462 arg1 RPLs 497:500 RPLs 497:500 RPLs 497:500 Amenability to recombinant expression in Escherichia coli simplifies their production and presents opportunities for further genetic manipulation to create novel recombinant prokaryotic lectins (RPLs) with altered or enhanced carbohydrate binding properties. 24462641 2 89 theme novel 458:462 arg1 lectins 488:494 novel recombinant prokaryotic lectins 458:494 novel recombinant prokaryotic lectins (RPLs) with altered or enhanced carbohydrate binding properties 458:558 Amenability to recombinant expression in Escherichia coli simplifies their production and presents opportunities for further genetic manipulation to create novel recombinant prokaryotic lectins (RPLs) with altered or enhanced carbohydrate binding properties. 24462641 0 90 theme prokaryotic 29:39 arg1 lectins 41:47 novel recombinant prokaryotic lectins 11:47 novel recombinant prokaryotic lectins with altered carbohydrate binding properties 11:92 Generating novel recombinant prokaryotic lectins with altered carbohydrate binding properties through mutagenesis of the PA-IL protein from Pseudomonas aeruginosa. 24462641 2 91 theme altered 508:514 arg1 properties 549:558 altered or enhanced carbohydrate binding properties 508:558 altered or enhanced carbohydrate binding properties 508:558 Amenability to recombinant expression in Escherichia coli simplifies their production and presents opportunities for further genetic manipulation to create novel recombinant prokaryotic lectins (RPLs) with altered or enhanced carbohydrate binding properties. 24462641 5 92 theme resulting 885:893 arg1 clones 906:911 The resulting expression clones 881:911 The resulting expression clones 881:911 The resulting expression clones were then functionally screened to identify clones expressing rPA-IL proteins with altered carbohydrate binding properties. 24462641 9 93 theme carbohydrate 1565:1576 arg1 properties 1586:1595 The carbohydrate binding properties 1561:1595 The carbohydrate binding properties of the PA-IL protein 1561:1616 CONCLUSIONS The carbohydrate binding properties of the PA-IL protein can be significantly altered using site-directed mutagenesis strategies to generate novel RPLs with diverse carbohydrate binding properties. 24462641 9 94 with RPLs 1708:1711 arg1 properties 1747:1756 diverse carbohydrate binding properties 1718:1756 diverse carbohydrate binding properties 1718:1756 CONCLUSIONS The carbohydrate binding properties of the PA-IL protein can be significantly altered using site-directed mutagenesis strategies to generate novel RPLs with diverse carbohydrate binding properties. 24462641 0 95 theme carbohydrate 62:73 arg1 properties 83:92 altered carbohydrate binding properties 54:92 altered carbohydrate binding properties 54:92 Generating novel recombinant prokaryotic lectins with altered carbohydrate binding properties through mutagenesis of the PA-IL protein from Pseudomonas aeruginosa. 24462641 10 96 from analysis 1885:1892 arg1 range 1823:1827 a broad range 1815:1827 a broad range of applications in glycobiology, diagnostics and in the analysis of biotherapeutics 1815:1911 GENERAL SIGNIFICANCE The novel RPLs reported would find a broad range of applications in glycobiology, diagnostics and in the analysis of biotherapeutics. 24462641 2 97 theme binding 541:547 arg1 properties 549:558 altered or enhanced carbohydrate binding properties 508:558 altered or enhanced carbohydrate binding properties 508:558 Amenability to recombinant expression in Escherichia coli simplifies their production and presents opportunities for further genetic manipulation to create novel recombinant prokaryotic lectins (RPLs) with altered or enhanced carbohydrate binding properties. 24462641 6 98 gly glycoprotein 1252:1263 arg1 glycoprotein 1252:1263 glycoprotein targets 1252:1271 glycoprotein targets 1252:1271 RESULTS This study generated RPLs exhibiting diverse carbohydrate binding activities including specificity and high affinity for β-linked galactose and N-acetyl-lactosamine (LacNAc) displayed by N-linked glycans on glycoprotein targets. 24462641 10 99 theme GENERAL 1759:1765 arg1 SIGNIFICANCE 1767:1778 GENERAL SIGNIFICANCE 1759:1778 GENERAL SIGNIFICANCE The novel RPLs reported 1759:1802 GENERAL SIGNIFICANCE The novel RPLs reported would find a broad range of applications in glycobiology, diagnostics and in the analysis of biotherapeutics. 24462641 11 100 theme gram 1959:1962 arg1 quantities 1964:1973 gram quantities 1959:1973 gram quantities 1959:1973 The ability to readily produce these RPLs in gram quantities could enable them to find larger scale applications for glycoprotein or biotherapeutic purification. 24462641 9 101 theme protein 1610:1616 arg1 properties 1586:1595 The carbohydrate binding properties 1561:1595 The carbohydrate binding properties of the PA-IL protein 1561:1616 CONCLUSIONS The carbohydrate binding properties of the PA-IL protein can be significantly altered using site-directed mutagenesis strategies to generate novel RPLs with diverse carbohydrate binding properties. 24462641 5 102 theme rPA-IL 975:980 arg1 proteins 982:989 rPA-IL proteins 975:989 rPA-IL proteins 975:989 The resulting expression clones were then functionally screened to identify clones expressing rPA-IL proteins with altered carbohydrate binding properties. 24462641 10 103 theme biotherapeutics 1897:1911 arg1 analysis 1885:1892 the analysis 1881:1892 the analysis of biotherapeutics 1881:1911 GENERAL SIGNIFICANCE The novel RPLs reported would find a broad range of applications in glycobiology, diagnostics and in the analysis of biotherapeutics. 24462641 6 104 dep RESULTS 1037:1043 arg1 generated 1056:1064 generated 1056:1064 generated RPLs exhibiting diverse carbohydrate binding activities including specificity and high affinity for β-linked galactose and N-acetyl-lactosamine (LacNAc) displayed by N-linked glycans on glycoprotein targets 1056:1271 RESULTS This study generated RPLs exhibiting diverse carbohydrate binding activities including specificity and high affinity for β-linked galactose and N-acetyl-lactosamine (LacNAc) displayed by N-linked glycans on glycoprotein targets. 24462641 3 105 theme PA-IL 618:622 arg1 lectin 624:629 the α-galactophilic PA-IL lectin 598:629 the α-galactophilic PA-IL lectin from Pseudomonas aeruginosa 598:657 This study explored the potential of the α-galactophilic PA-IL lectin from Pseudomonas aeruginosa for use as a scaffold structure for the generation of novel RPLs. 24462641 1 106 theme tools 295:299 arg1 development 256:266 the development 252:266 the development of enhanced glycoselective tools 252:299 BACKGROUND Prokaryotic lectins offer significant advantages over eukaryotic lectins for the development of enhanced glycoselective tools. 24060503 6 0 theme wide 969:972 arg1 distribution 981:992 a wide tissue distribution 967:992 a wide tissue distribution of an estimated 3 kbp calnexin transcript with an additional minor transcript of 2.3 kbp 967:1081 Southern blotting revealed that there are at least two copies of the calnexin gene in the trout genome and northern blotting showed a wide tissue distribution of an estimated 3 kbp calnexin transcript with an additional minor transcript of 2.3 kbp expressed only in head kidney, spleen PBLs and strongly in RTS11. 24060503 1 1 theme membrane 130:137 arg1 Calnexin 95:102 Calnexin (IP90/P88) 95:113 Calnexin (IP90/P88) 95:113 Calnexin (IP90/P88) is an integral membrane protein of the endoplasmic reticulum that binds newly synthesized N-linked glycoproteins during their folding in the ER including MHC class I molecule. 24060503 1 1 theme membrane 130:137 arg1 protein 139:145 an integral membrane protein 118:145 an integral membrane protein of the endoplasmic reticulum that binds newly synthesized N-linked glycoproteins during their folding in the ER including MHC class I molecule 118:288 Calnexin (IP90/P88) is an integral membrane protein of the endoplasmic reticulum that binds newly synthesized N-linked glycoproteins during their folding in the ER including MHC class I molecule. 24060503 6 2 theme Southern 835:842 arg1 blotting 844:851 Southern blotting 835:851 Southern blotting 835:851 Southern blotting revealed that there are at least two copies of the calnexin gene in the trout genome and northern blotting showed a wide tissue distribution of an estimated 3 kbp calnexin transcript with an additional minor transcript of 2.3 kbp expressed only in head kidney, spleen PBLs and strongly in RTS11. 24060503 6 3 theme trout 925:929 arg1 genome 931:936 the trout genome 921:936 the trout genome 921:936 Southern blotting revealed that there are at least two copies of the calnexin gene in the trout genome and northern blotting showed a wide tissue distribution of an estimated 3 kbp calnexin transcript with an additional minor transcript of 2.3 kbp expressed only in head kidney, spleen PBLs and strongly in RTS11. 24060503 6 4 theme tissue 974:979 arg1 distribution 981:992 a wide tissue distribution 967:992 a wide tissue distribution of an estimated 3 kbp calnexin transcript with an additional minor transcript of 2.3 kbp 967:1081 Southern blotting revealed that there are at least two copies of the calnexin gene in the trout genome and northern blotting showed a wide tissue distribution of an estimated 3 kbp calnexin transcript with an additional minor transcript of 2.3 kbp expressed only in head kidney, spleen PBLs and strongly in RTS11. 24060503 0 5 contain contain 36:42 arg2 proteins 85:92 distinct proteins 76:92 distinct proteins 76:92 Rainbow trout (Oncorhynchus mykiss) contain two calnexin genes which encode distinct proteins. 24060503 0 5 contain contain 36:42 arg1 mykiss 28:33 Oncorhynchus mykiss 15:33 Oncorhynchus mykiss 15:33 Rainbow trout (Oncorhynchus mykiss) contain two calnexin genes which encode distinct proteins. 24060503 0 5 contain contain 36:42 arg1 trout 8:12 Rainbow trout 0:12 Rainbow trout (Oncorhynchus mykiss) 0:34 Rainbow trout (Oncorhynchus mykiss) contain two calnexin genes which encode distinct proteins. 24060503 0 5 contain contain 36:42 arg2 genes 57:61 two calnexin genes 44:61 two calnexin genes which encode distinct proteins 44:92 Rainbow trout (Oncorhynchus mykiss) contain two calnexin genes which encode distinct proteins. 24060503 3 6 theme putative 402:409 arg1 proteins 418:425 putative mature proteins 402:425 putative mature proteins of 579 and 592 aa 402:443 Both encode putative mature proteins of 579 and 592 aa respectively in addition to a 24 aa signal peptide. 24060503 3 6 theme putative 402:409 arg1 Both 390:393 Both 390:393 Both 390:393 Both encode putative mature proteins of 579 and 592 aa respectively in addition to a 24 aa signal peptide. 24060503 6 7 theme kbp 1012:1014 arg1 transcript 1025:1034 an estimated 3 kbp calnexin transcript 997:1034 an estimated 3 kbp calnexin transcript with an additional minor transcript of 2.3 kbp 997:1081 Southern blotting revealed that there are at least two copies of the calnexin gene in the trout genome and northern blotting showed a wide tissue distribution of an estimated 3 kbp calnexin transcript with an additional minor transcript of 2.3 kbp expressed only in head kidney, spleen PBLs and strongly in RTS11. 24060503 9 8 theme calnexin 1511:1518 arg1 gene 1520:1523 the calnexin gene 1507:1523 the calnexin gene 1507:1523 These results suggest that in salmonids there are two differentiated versions of the calnexin gene which encode proteins that may have diverged to perform unique biological functions. 24060503 2 9 from clones 353:358 arg1 trout 383:387 rainbow trout 375:387 rainbow trout 375:387 This manuscript reports the identification of two unique cDNA clones of calnexin in rainbow trout. 24060503 6 10 theme head 1101:1104 arg1 kidney 1106:1111 head kidney 1101:1111 head kidney 1101:1111 Southern blotting revealed that there are at least two copies of the calnexin gene in the trout genome and northern blotting showed a wide tissue distribution of an estimated 3 kbp calnexin transcript with an additional minor transcript of 2.3 kbp expressed only in head kidney, spleen PBLs and strongly in RTS11. 24060503 6 10 theme head 1101:1104 arg1 PBLs 1121:1124 spleen PBLs 1114:1124 spleen PBLs 1114:1124 Southern blotting revealed that there are at least two copies of the calnexin gene in the trout genome and northern blotting showed a wide tissue distribution of an estimated 3 kbp calnexin transcript with an additional minor transcript of 2.3 kbp expressed only in head kidney, spleen PBLs and strongly in RTS11. 24060503 8 11 theme western 1284:1290 arg1 blots 1292:1296 western blots 1284:1296 western blots 1284:1296 In western blots, calnexin was detected primarily as a 120 kDa protein and upon A23187 treatment; a 100 kDa band was most prominently expressed. 24060503 4 12 theme cDNA 549:552 arg1 clones 554:559 the two cDNA clones 541:559 the two cDNA clones 541:559 Sequence analysis revealed that only one of the two cDNA clones encodes a putative ER retention signal, K/QEDDL, followed by a serine phosphorylation site conserved with mammalian homologs. 24060503 0 13 theme distinct 76:83 arg1 proteins 85:92 distinct proteins 76:92 distinct proteins 76:92 Rainbow trout (Oncorhynchus mykiss) contain two calnexin genes which encode distinct proteins. 24060503 0 13 theme distinct 76:83 arg1 genes 57:61 two calnexin genes 44:61 two calnexin genes which encode distinct proteins 44:92 Rainbow trout (Oncorhynchus mykiss) contain two calnexin genes which encode distinct proteins. 24060503 4 14 theme ER 580:581 arg1 signal 593:598 a putative ER retention signal 569:598 a putative ER retention signal 569:598 Sequence analysis revealed that only one of the two cDNA clones encodes a putative ER retention signal, K/QEDDL, followed by a serine phosphorylation site conserved with mammalian homologs. 24060503 4 14 theme ER 580:581 arg1 clones 554:559 the two cDNA clones 541:559 the two cDNA clones 541:559 Sequence analysis revealed that only one of the two cDNA clones encodes a putative ER retention signal, K/QEDDL, followed by a serine phosphorylation site conserved with mammalian homologs. 24060503 4 14 theme ER 580:581 arg1 K/QEDDL 601:607 K/QEDDL 601:607 K/QEDDL 601:607 Sequence analysis revealed that only one of the two cDNA clones encodes a putative ER retention signal, K/QEDDL, followed by a serine phosphorylation site conserved with mammalian homologs. 24060503 4 14 theme ER 580:581 arg1 one 534:536 one 534:536 one 534:536 Sequence analysis revealed that only one of the two cDNA clones encodes a putative ER retention signal, K/QEDDL, followed by a serine phosphorylation site conserved with mammalian homologs. 24060503 6 15 theme gene 913:916 arg1 copies 890:895 at least two copies 877:895 at least two copies of the calnexin gene 877:916 Southern blotting revealed that there are at least two copies of the calnexin gene in the trout genome and northern blotting showed a wide tissue distribution of an estimated 3 kbp calnexin transcript with an additional minor transcript of 2.3 kbp expressed only in head kidney, spleen PBLs and strongly in RTS11. 24060503 2 16 theme unique 341:346 arg1 clones 353:358 two unique cDNA clones 337:358 two unique cDNA clones of calnexin in rainbow trout 337:387 This manuscript reports the identification of two unique cDNA clones of calnexin in rainbow trout. 24060503 4 17 theme mammalian 667:675 arg1 homologs 677:684 mammalian homologs 667:684 mammalian homologs 667:684 Sequence analysis revealed that only one of the two cDNA clones encodes a putative ER retention signal, K/QEDDL, followed by a serine phosphorylation site conserved with mammalian homologs. 24060503 5 18 theme acid 693:696 arg1 alignment 707:715 Amino acid sequence alignment 687:715 Amino acid sequence alignment 687:715 Amino acid sequence alignment illustrated conservation of the calnexin luminal domain, which consists of a globular and a P domain, in both copies. 24060503 3 19 theme aa 442:443 arg1 proteins 418:425 putative mature proteins 402:425 putative mature proteins of 579 and 592 aa 402:443 Both encode putative mature proteins of 579 and 592 aa respectively in addition to a 24 aa signal peptide. 24060503 3 19 theme aa 442:443 arg1 Both 390:393 Both 390:393 Both 390:393 Both encode putative mature proteins of 579 and 592 aa respectively in addition to a 24 aa signal peptide. 24060503 1 20 theme endoplasmic 154:164 arg1 reticulum 166:174 the endoplasmic reticulum 150:174 the endoplasmic reticulum 150:174 Calnexin (IP90/P88) is an integral membrane protein of the endoplasmic reticulum that binds newly synthesized N-linked glycoproteins during their folding in the ER including MHC class I molecule. 24060503 2 21 theme rainbow 375:381 arg1 trout 383:387 rainbow trout 375:387 rainbow trout 375:387 This manuscript reports the identification of two unique cDNA clones of calnexin in rainbow trout. 24060503 5 22 theme sequence 698:705 arg1 alignment 707:715 Amino acid sequence alignment 687:715 Amino acid sequence alignment 687:715 Amino acid sequence alignment illustrated conservation of the calnexin luminal domain, which consists of a globular and a P domain, in both copies. 24060503 6 23 with transcript 1025:1034 arg1 transcript 1061:1070 an additional minor transcript 1041:1070 an additional minor transcript of 2.3 kbp 1041:1081 Southern blotting revealed that there are at least two copies of the calnexin gene in the trout genome and northern blotting showed a wide tissue distribution of an estimated 3 kbp calnexin transcript with an additional minor transcript of 2.3 kbp expressed only in head kidney, spleen PBLs and strongly in RTS11. 24060503 6 24 theme northern 942:949 arg1 blotting 951:958 northern blotting 942:958 northern blotting 942:958 Southern blotting revealed that there are at least two copies of the calnexin gene in the trout genome and northern blotting showed a wide tissue distribution of an estimated 3 kbp calnexin transcript with an additional minor transcript of 2.3 kbp expressed only in head kidney, spleen PBLs and strongly in RTS11. 24060503 6 25 theme 3 1010:1010 arg1 kbp 1012:1014 kbp 1012:1014 kbp 1012:1014 Southern blotting revealed that there are at least two copies of the calnexin gene in the trout genome and northern blotting showed a wide tissue distribution of an estimated 3 kbp calnexin transcript with an additional minor transcript of 2.3 kbp expressed only in head kidney, spleen PBLs and strongly in RTS11. 24060503 3 26 theme signal 481:486 arg1 peptide 488:494 a 24 aa signal peptide 473:494 a 24 aa signal peptide 473:494 Both encode putative mature proteins of 579 and 592 aa respectively in addition to a 24 aa signal peptide. 24060503 6 27 theme estimated 1000:1008 arg1 transcript 1025:1034 an estimated 3 kbp calnexin transcript 997:1034 an estimated 3 kbp calnexin transcript with an additional minor transcript of 2.3 kbp 997:1081 Southern blotting revealed that there are at least two copies of the calnexin gene in the trout genome and northern blotting showed a wide tissue distribution of an estimated 3 kbp calnexin transcript with an additional minor transcript of 2.3 kbp expressed only in head kidney, spleen PBLs and strongly in RTS11. 24060503 6 28 theme kbp 1079:1081 arg1 transcript 1061:1070 an additional minor transcript 1041:1070 an additional minor transcript of 2.3 kbp 1041:1081 Southern blotting revealed that there are at least two copies of the calnexin gene in the trout genome and northern blotting showed a wide tissue distribution of an estimated 3 kbp calnexin transcript with an additional minor transcript of 2.3 kbp expressed only in head kidney, spleen PBLs and strongly in RTS11. 24060503 2 29 theme calnexin 363:370 arg1 clones 353:358 two unique cDNA clones 337:358 two unique cDNA clones of calnexin in rainbow trout 337:387 This manuscript reports the identification of two unique cDNA clones of calnexin in rainbow trout. 24060503 0 30 theme Rainbow 0:6 arg1 trout 8:12 Rainbow trout 0:12 Rainbow trout (Oncorhynchus mykiss) 0:34 Rainbow trout (Oncorhynchus mykiss) contain two calnexin genes which encode distinct proteins. 24060503 0 30 theme Rainbow 0:6 arg1 mykiss 28:33 Oncorhynchus mykiss 15:33 Oncorhynchus mykiss 15:33 Rainbow trout (Oncorhynchus mykiss) contain two calnexin genes which encode distinct proteins. 24060503 6 31 theme calnexin 904:911 arg1 gene 913:916 the calnexin gene 900:916 the calnexin gene 900:916 Southern blotting revealed that there are at least two copies of the calnexin gene in the trout genome and northern blotting showed a wide tissue distribution of an estimated 3 kbp calnexin transcript with an additional minor transcript of 2.3 kbp expressed only in head kidney, spleen PBLs and strongly in RTS11. 24060503 1 32 link N-linked 205:212 arg1 glycoproteins 214:226 newly synthesized N-linked glycoproteins 187:226 newly synthesized N-linked glycoproteins 187:226 Calnexin (IP90/P88) is an integral membrane protein of the endoplasmic reticulum that binds newly synthesized N-linked glycoproteins during their folding in the ER including MHC class I molecule. 24060503 1 33 theme reticulum 166:174 arg1 Calnexin 95:102 Calnexin (IP90/P88) 95:113 Calnexin (IP90/P88) 95:113 Calnexin (IP90/P88) is an integral membrane protein of the endoplasmic reticulum that binds newly synthesized N-linked glycoproteins during their folding in the ER including MHC class I molecule. 24060503 1 33 theme reticulum 166:174 arg1 protein 139:145 an integral membrane protein 118:145 an integral membrane protein of the endoplasmic reticulum that binds newly synthesized N-linked glycoproteins during their folding in the ER including MHC class I molecule 118:288 Calnexin (IP90/P88) is an integral membrane protein of the endoplasmic reticulum that binds newly synthesized N-linked glycoproteins during their folding in the ER including MHC class I molecule. 24060503 0 34 theme Oncorhynchus 15:26 arg1 trout 8:12 Rainbow trout 0:12 Rainbow trout (Oncorhynchus mykiss) 0:34 Rainbow trout (Oncorhynchus mykiss) contain two calnexin genes which encode distinct proteins. 24060503 0 34 theme Oncorhynchus 15:26 arg1 mykiss 28:33 Oncorhynchus mykiss 15:33 Oncorhynchus mykiss 15:33 Rainbow trout (Oncorhynchus mykiss) contain two calnexin genes which encode distinct proteins. 24060503 1 35 theme MHC 269:271 arg1 class 273:277 MHC class I 269:279 MHC class I molecule 269:288 Calnexin (IP90/P88) is an integral membrane protein of the endoplasmic reticulum that binds newly synthesized N-linked glycoproteins during their folding in the ER including MHC class I molecule. 24060503 9 36 theme unique 1581:1586 arg1 functions 1599:1607 unique biological functions 1581:1607 unique biological functions 1581:1607 These results suggest that in salmonids there are two differentiated versions of the calnexin gene which encode proteins that may have diverged to perform unique biological functions. 24060503 1 37 gly glycoproteins 214:226 arg1 glycoproteins 214:226 newly synthesized N-linked glycoproteins 187:226 newly synthesized N-linked glycoproteins 187:226 Calnexin (IP90/P88) is an integral membrane protein of the endoplasmic reticulum that binds newly synthesized N-linked glycoproteins during their folding in the ER including MHC class I molecule. 24060503 4 38 theme retention 583:591 arg1 signal 593:598 a putative ER retention signal 569:598 a putative ER retention signal 569:598 Sequence analysis revealed that only one of the two cDNA clones encodes a putative ER retention signal, K/QEDDL, followed by a serine phosphorylation site conserved with mammalian homologs. 24060503 4 38 theme retention 583:591 arg1 clones 554:559 the two cDNA clones 541:559 the two cDNA clones 541:559 Sequence analysis revealed that only one of the two cDNA clones encodes a putative ER retention signal, K/QEDDL, followed by a serine phosphorylation site conserved with mammalian homologs. 24060503 4 38 theme retention 583:591 arg1 K/QEDDL 601:607 K/QEDDL 601:607 K/QEDDL 601:607 Sequence analysis revealed that only one of the two cDNA clones encodes a putative ER retention signal, K/QEDDL, followed by a serine phosphorylation site conserved with mammalian homologs. 24060503 4 38 theme retention 583:591 arg1 one 534:536 one 534:536 one 534:536 Sequence analysis revealed that only one of the two cDNA clones encodes a putative ER retention signal, K/QEDDL, followed by a serine phosphorylation site conserved with mammalian homologs. 24060503 8 39 located detected 1312:1319 arg2 calnexin 1299:1306 calnexin 1299:1306 calnexin 1299:1306 In western blots, calnexin was detected primarily as a 120 kDa protein and upon A23187 treatment; a 100 kDa band was most prominently expressed. 24060503 8 39 located detected 1312:1319 arg1 blots 1292:1296 western blots 1284:1296 western blots 1284:1296 In western blots, calnexin was detected primarily as a 120 kDa protein and upon A23187 treatment; a 100 kDa band was most prominently expressed. 24060503 1 40 theme class 273:277 arg1 molecule 281:288 MHC class I molecule 269:288 MHC class I molecule 269:288 Calnexin (IP90/P88) is an integral membrane protein of the endoplasmic reticulum that binds newly synthesized N-linked glycoproteins during their folding in the ER including MHC class I molecule. 24060503 6 41 dep showed 960:965 arg1 expressed 1083:1091 expressed 1083:1091 showed a wide tissue distribution of an estimated 3 kbp calnexin transcript with an additional minor transcript of 2.3 kbp expressed only in head kidney, spleen PBLs and strongly in RTS11 960:1146 Southern blotting revealed that there are at least two copies of the calnexin gene in the trout genome and northern blotting showed a wide tissue distribution of an estimated 3 kbp calnexin transcript with an additional minor transcript of 2.3 kbp expressed only in head kidney, spleen PBLs and strongly in RTS11. 24060503 4 42 theme phosphorylation 631:645 arg1 site 647:650 a serine phosphorylation site 622:650 a serine phosphorylation site conserved with mammalian homologs 622:684 Sequence analysis revealed that only one of the two cDNA clones encodes a putative ER retention signal, K/QEDDL, followed by a serine phosphorylation site conserved with mammalian homologs. 24060503 3 43 theme aa 478:479 arg1 peptide 488:494 a 24 aa signal peptide 473:494 a 24 aa signal peptide 473:494 Both encode putative mature proteins of 579 and 592 aa respectively in addition to a 24 aa signal peptide. 24060503 6 44 theme transcript 1025:1034 arg1 distribution 981:992 a wide tissue distribution 967:992 a wide tissue distribution of an estimated 3 kbp calnexin transcript with an additional minor transcript of 2.3 kbp 967:1081 Southern blotting revealed that there are at least two copies of the calnexin gene in the trout genome and northern blotting showed a wide tissue distribution of an estimated 3 kbp calnexin transcript with an additional minor transcript of 2.3 kbp expressed only in head kidney, spleen PBLs and strongly in RTS11. 24060503 1 45 from folding 241:247 arg1 ER 256:257 the ER 252:257 the ER 252:257 Calnexin (IP90/P88) is an integral membrane protein of the endoplasmic reticulum that binds newly synthesized N-linked glycoproteins during their folding in the ER including MHC class I molecule. 24060503 8 46 theme kDa 1340:1342 arg1 protein 1344:1350 a 120 kDa protein 1334:1350 a 120 kDa protein 1334:1350 In western blots, calnexin was detected primarily as a 120 kDa protein and upon A23187 treatment; a 100 kDa band was most prominently expressed. 24060503 3 47 theme mature 411:416 arg1 proteins 418:425 putative mature proteins 402:425 putative mature proteins of 579 and 592 aa 402:443 Both encode putative mature proteins of 579 and 592 aa respectively in addition to a 24 aa signal peptide. 24060503 3 47 theme mature 411:416 arg1 Both 390:393 Both 390:393 Both 390:393 Both encode putative mature proteins of 579 and 592 aa respectively in addition to a 24 aa signal peptide. 24060503 4 48 theme serine 624:629 arg1 site 647:650 a serine phosphorylation site 622:650 a serine phosphorylation site conserved with mammalian homologs 622:684 Sequence analysis revealed that only one of the two cDNA clones encodes a putative ER retention signal, K/QEDDL, followed by a serine phosphorylation site conserved with mammalian homologs. 24060503 5 49 theme calnexin 749:756 arg1 domain 766:771 the calnexin luminal domain 745:771 the calnexin luminal domain 745:771 Amino acid sequence alignment illustrated conservation of the calnexin luminal domain, which consists of a globular and a P domain, in both copies. 24060503 9 50 theme differentiated 1480:1493 arg1 versions 1495:1502 two differentiated versions 1476:1502 two differentiated versions of the calnexin gene which encode proteins that may have diverged to perform unique biological functions 1476:1607 These results suggest that in salmonids there are two differentiated versions of the calnexin gene which encode proteins that may have diverged to perform unique biological functions. 24060503 9 50 theme differentiated 1480:1493 arg1 proteins 1538:1545 proteins 1538:1545 proteins that may have diverged to perform unique biological functions 1538:1607 These results suggest that in salmonids there are two differentiated versions of the calnexin gene which encode proteins that may have diverged to perform unique biological functions. 24060503 2 51 from calnexin 363:370 arg1 trout 383:387 rainbow trout 375:387 rainbow trout 375:387 This manuscript reports the identification of two unique cDNA clones of calnexin in rainbow trout. 24060503 1 52 theme synthesized 193:203 arg1 glycoproteins 214:226 newly synthesized N-linked glycoproteins 187:226 newly synthesized N-linked glycoproteins 187:226 Calnexin (IP90/P88) is an integral membrane protein of the endoplasmic reticulum that binds newly synthesized N-linked glycoproteins during their folding in the ER including MHC class I molecule. 24060503 5 53 theme luminal 758:764 arg1 domain 766:771 the calnexin luminal domain 745:771 the calnexin luminal domain 745:771 Amino acid sequence alignment illustrated conservation of the calnexin luminal domain, which consists of a globular and a P domain, in both copies. 24060503 6 54 theme calnexin 1016:1023 arg1 transcript 1025:1034 an estimated 3 kbp calnexin transcript 997:1034 an estimated 3 kbp calnexin transcript with an additional minor transcript of 2.3 kbp 997:1081 Southern blotting revealed that there are at least two copies of the calnexin gene in the trout genome and northern blotting showed a wide tissue distribution of an estimated 3 kbp calnexin transcript with an additional minor transcript of 2.3 kbp expressed only in head kidney, spleen PBLs and strongly in RTS11. 24060503 6 55 theme minor 1055:1059 arg1 transcript 1061:1070 an additional minor transcript 1041:1070 an additional minor transcript of 2.3 kbp 1041:1081 Southern blotting revealed that there are at least two copies of the calnexin gene in the trout genome and northern blotting showed a wide tissue distribution of an estimated 3 kbp calnexin transcript with an additional minor transcript of 2.3 kbp expressed only in head kidney, spleen PBLs and strongly in RTS11. 24060503 5 56 theme domain 766:771 arg1 conservation 729:740 conservation 729:740 conservation of the calnexin luminal domain, which consists of a globular and a P domain, in both copies 729:832 Amino acid sequence alignment illustrated conservation of the calnexin luminal domain, which consists of a globular and a P domain, in both copies. 24060503 7 57 theme 24h 1232:1234 arg1 treatment 1236:1244 a 24h treatment 1230:1244 a 24h treatment with the calcium ionophore A23187 1230:1278 Importantly, the smaller transcript was predominantly upregulated in RTS11 after a 24h treatment with the calcium ionophore A23187. 24060503 5 58 from conservation 729:740 arg1 copies 827:832 both copies 822:832 both copies 822:832 Amino acid sequence alignment illustrated conservation of the calnexin luminal domain, which consists of a globular and a P domain, in both copies. 24060503 9 59 theme gene 1520:1523 arg1 versions 1495:1502 two differentiated versions 1476:1502 two differentiated versions of the calnexin gene which encode proteins that may have diverged to perform unique biological functions 1476:1607 These results suggest that in salmonids there are two differentiated versions of the calnexin gene which encode proteins that may have diverged to perform unique biological functions. 24060503 9 59 theme gene 1520:1523 arg1 proteins 1538:1545 proteins 1538:1545 proteins that may have diverged to perform unique biological functions 1538:1607 These results suggest that in salmonids there are two differentiated versions of the calnexin gene which encode proteins that may have diverged to perform unique biological functions. 24060503 6 60 theme additional 1044:1053 arg1 transcript 1061:1070 an additional minor transcript 1041:1070 an additional minor transcript of 2.3 kbp 1041:1081 Southern blotting revealed that there are at least two copies of the calnexin gene in the trout genome and northern blotting showed a wide tissue distribution of an estimated 3 kbp calnexin transcript with an additional minor transcript of 2.3 kbp expressed only in head kidney, spleen PBLs and strongly in RTS11. 24060503 4 61 theme Sequence 497:504 arg1 analysis 506:513 Sequence analysis 497:513 Sequence analysis 497:513 Sequence analysis revealed that only one of the two cDNA clones encodes a putative ER retention signal, K/QEDDL, followed by a serine phosphorylation site conserved with mammalian homologs. 24060503 7 62 with treatment 1236:1244 arg1 A23187 1273:1278 the calcium ionophore A23187 1251:1278 the calcium ionophore A23187 1251:1278 Importantly, the smaller transcript was predominantly upregulated in RTS11 after a 24h treatment with the calcium ionophore A23187. 24060503 8 63 theme A23187 1361:1366 arg1 treatment 1368:1376 A23187 treatment 1361:1376 A23187 treatment 1361:1376 In western blots, calnexin was detected primarily as a 120 kDa protein and upon A23187 treatment; a 100 kDa band was most prominently expressed. 24060503 7 64 theme ionophore 1263:1271 arg1 A23187 1273:1278 the calcium ionophore A23187 1251:1278 the calcium ionophore A23187 1251:1278 Importantly, the smaller transcript was predominantly upregulated in RTS11 after a 24h treatment with the calcium ionophore A23187. 24060503 7 65 theme smaller 1166:1172 arg1 transcript 1174:1183 the smaller transcript 1162:1183 the smaller transcript 1162:1183 Importantly, the smaller transcript was predominantly upregulated in RTS11 after a 24h treatment with the calcium ionophore A23187. 24060503 1 66 theme N-linked 205:212 arg1 glycoproteins 214:226 newly synthesized N-linked glycoproteins 187:226 newly synthesized N-linked glycoproteins 187:226 Calnexin (IP90/P88) is an integral membrane protein of the endoplasmic reticulum that binds newly synthesized N-linked glycoproteins during their folding in the ER including MHC class I molecule. 24060503 6 67 theme spleen 1114:1119 arg1 kidney 1106:1111 head kidney 1101:1111 head kidney 1101:1111 Southern blotting revealed that there are at least two copies of the calnexin gene in the trout genome and northern blotting showed a wide tissue distribution of an estimated 3 kbp calnexin transcript with an additional minor transcript of 2.3 kbp expressed only in head kidney, spleen PBLs and strongly in RTS11. 24060503 6 67 theme spleen 1114:1119 arg1 PBLs 1121:1124 spleen PBLs 1114:1124 spleen PBLs 1114:1124 Southern blotting revealed that there are at least two copies of the calnexin gene in the trout genome and northern blotting showed a wide tissue distribution of an estimated 3 kbp calnexin transcript with an additional minor transcript of 2.3 kbp expressed only in head kidney, spleen PBLs and strongly in RTS11. 24060503 5 68 theme P 809:809 arg1 domain 811:816 a globular and a P domain 792:816 domain 811:816 Amino acid sequence alignment illustrated conservation of the calnexin luminal domain, which consists of a globular and a P domain, in both copies. 24060503 2 69 theme cDNA 348:351 arg1 clones 353:358 two unique cDNA clones 337:358 two unique cDNA clones of calnexin in rainbow trout 337:387 This manuscript reports the identification of two unique cDNA clones of calnexin in rainbow trout. 24060503 4 70 theme clones 554:559 arg1 signal 593:598 a putative ER retention signal 569:598 a putative ER retention signal 569:598 Sequence analysis revealed that only one of the two cDNA clones encodes a putative ER retention signal, K/QEDDL, followed by a serine phosphorylation site conserved with mammalian homologs. 24060503 4 70 theme clones 554:559 arg1 clones 554:559 the two cDNA clones 541:559 the two cDNA clones 541:559 Sequence analysis revealed that only one of the two cDNA clones encodes a putative ER retention signal, K/QEDDL, followed by a serine phosphorylation site conserved with mammalian homologs. 24060503 4 70 theme clones 554:559 arg1 one 534:536 one 534:536 one 534:536 Sequence analysis revealed that only one of the two cDNA clones encodes a putative ER retention signal, K/QEDDL, followed by a serine phosphorylation site conserved with mammalian homologs. 24060503 5 71 theme a 807:807 arg1 domain 811:816 a globular and a P domain 792:816 domain 811:816 Amino acid sequence alignment illustrated conservation of the calnexin luminal domain, which consists of a globular and a P domain, in both copies. 24060503 8 72 theme 120 1336:1338 arg1 kDa 1340:1342 kDa 1340:1342 kDa 1340:1342 In western blots, calnexin was detected primarily as a 120 kDa protein and upon A23187 treatment; a 100 kDa band was most prominently expressed. 24060503 2 73 from trout 383:387 arg1 clones 353:358 two unique cDNA clones 337:358 two unique cDNA clones of calnexin in rainbow trout 337:387 This manuscript reports the identification of two unique cDNA clones of calnexin in rainbow trout. 24060503 2 74 theme clones 353:358 arg1 identification 319:332 the identification 315:332 the identification of two unique cDNA clones of calnexin in rainbow trout 315:387 This manuscript reports the identification of two unique cDNA clones of calnexin in rainbow trout. 24060503 4 75 theme putative 571:578 arg1 signal 593:598 a putative ER retention signal 569:598 a putative ER retention signal 569:598 Sequence analysis revealed that only one of the two cDNA clones encodes a putative ER retention signal, K/QEDDL, followed by a serine phosphorylation site conserved with mammalian homologs. 24060503 4 75 theme putative 571:578 arg1 clones 554:559 the two cDNA clones 541:559 the two cDNA clones 541:559 Sequence analysis revealed that only one of the two cDNA clones encodes a putative ER retention signal, K/QEDDL, followed by a serine phosphorylation site conserved with mammalian homologs. 24060503 4 75 theme putative 571:578 arg1 K/QEDDL 601:607 K/QEDDL 601:607 K/QEDDL 601:607 Sequence analysis revealed that only one of the two cDNA clones encodes a putative ER retention signal, K/QEDDL, followed by a serine phosphorylation site conserved with mammalian homologs. 24060503 4 75 theme putative 571:578 arg1 one 534:536 one 534:536 one 534:536 Sequence analysis revealed that only one of the two cDNA clones encodes a putative ER retention signal, K/QEDDL, followed by a serine phosphorylation site conserved with mammalian homologs. 24060503 0 76 theme calnexin 48:55 arg1 proteins 85:92 distinct proteins 76:92 distinct proteins 76:92 Rainbow trout (Oncorhynchus mykiss) contain two calnexin genes which encode distinct proteins. 24060503 0 76 theme calnexin 48:55 arg1 genes 57:61 two calnexin genes 44:61 two calnexin genes which encode distinct proteins 44:92 Rainbow trout (Oncorhynchus mykiss) contain two calnexin genes which encode distinct proteins. 24060503 8 77 theme kDa 1385:1387 arg1 band 1389:1392 a 100 kDa band 1379:1392 a 100 kDa band 1379:1392 In western blots, calnexin was detected primarily as a 120 kDa protein and upon A23187 treatment; a 100 kDa band was most prominently expressed. 24060503 7 78 theme calcium 1255:1261 arg1 A23187 1273:1278 the calcium ionophore A23187 1251:1278 the calcium ionophore A23187 1251:1278 Importantly, the smaller transcript was predominantly upregulated in RTS11 after a 24h treatment with the calcium ionophore A23187. 24060503 1 79 theme integral 121:128 arg1 Calnexin 95:102 Calnexin (IP90/P88) 95:113 Calnexin (IP90/P88) 95:113 Calnexin (IP90/P88) is an integral membrane protein of the endoplasmic reticulum that binds newly synthesized N-linked glycoproteins during their folding in the ER including MHC class I molecule. 24060503 1 79 theme integral 121:128 arg1 protein 139:145 an integral membrane protein 118:145 an integral membrane protein of the endoplasmic reticulum that binds newly synthesized N-linked glycoproteins during their folding in the ER including MHC class I molecule 118:288 Calnexin (IP90/P88) is an integral membrane protein of the endoplasmic reticulum that binds newly synthesized N-linked glycoproteins during their folding in the ER including MHC class I molecule. 24060503 9 80 theme biological 1588:1597 arg1 functions 1599:1607 unique biological functions 1581:1607 unique biological functions 1581:1607 These results suggest that in salmonids there are two differentiated versions of the calnexin gene which encode proteins that may have diverged to perform unique biological functions. 24060503 5 81 theme Amino 687:691 arg1 alignment 707:715 Amino acid sequence alignment 687:715 Amino acid sequence alignment 687:715 Amino acid sequence alignment illustrated conservation of the calnexin luminal domain, which consists of a globular and a P domain, in both copies. 28235995 6 0 theme glycopeptides 906:918 arg1 enrichment 920:929 glycopeptides enrichment 906:929 glycopeptides enrichment 906:929 These hydrazide - functionalized materials are applied to fetuin digest for glycopeptides enrichment and subsequently for selectivity and sensitivity assessment. 28235995 11 1 dep specificity 1619:1629 arg1 the 1615:1617 the 1615:1617 the 1615:1617 The hydrazide group density on cellulose, poly(GMA/DVB), and diamond is 2.8, 2.3, and 2.1 mmol/g, respectively; this contributes towards the specificity and sensitivity of designed materials. 28235995 13 2 theme surface 1863:1869 arg1 modifications 1871:1883 the economical surface modifications 1848:1883 the economical surface modifications of support materials 1848:1904 Therefore this study provides routes for the economical surface modifications of support materials and to fabricate affinity materials with improved efficiency. 28235995 2 3 theme compatible 325:334 arg1 protocols 315:323 surface modification protocols 294:323 surface modification protocols compatible to conventional support materials like silica and cellulose 294:394 A few hydrazide - functionalized materials with surface modification protocols compatible to conventional support materials like silica and cellulose are reported. 28235995 14 4 theme Graphical 1968:1976 arg1 Glycopeptides 1987:1999 Graphical Abstract Glycopeptides 1968:1999 Graphical Abstract Glycopeptides 1968:1999 Graphical Abstract Glycopeptides enrichment by hydrazine affinity. 28235995 11 5 theme group 1492:1496 arg1 2.8 1550:1552 2.8 1550:1552 2.8 1550:1552 The hydrazide group density on cellulose, poly(GMA/DVB), and diamond is 2.8, 2.3, and 2.1 mmol/g, respectively; this contributes towards the specificity and sensitivity of designed materials. 28235995 11 5 theme group 1492:1496 arg1 density 1498:1504 The hydrazide group density 1478:1504 The hydrazide group density on cellulose, poly(GMA/DVB), and diamond 1478:1545 The hydrazide group density on cellulose, poly(GMA/DVB), and diamond is 2.8, 2.3, and 2.1 mmol/g, respectively; this contributes towards the specificity and sensitivity of designed materials. 28235995 2 6 theme modification 302:313 arg1 protocols 315:323 surface modification protocols 294:323 surface modification protocols compatible to conventional support materials like silica and cellulose 294:394 A few hydrazide - functionalized materials with surface modification protocols compatible to conventional support materials like silica and cellulose are reported. 28235995 14 7 theme hydrazine 2015:2023 arg1 affinity 2025:2032 hydrazine affinity 2015:2032 hydrazine affinity 2015:2032 Graphical Abstract Glycopeptides enrichment by hydrazine affinity. 28235995 10 8 gly mono-N-linked-glycosylated 1380:1405 arg1 peptide 1407:1413 mono-N-linked-glycosylated peptide 1380:1413 mono-N-linked-glycosylated peptide from tryptic digest of chicken avidin spiked in fetuin digest 1380:1475 The materials enrich mono-N-linked-glycosylated peptide from tryptic digest of chicken avidin spiked in fetuin digest. 28235995 4 9 theme support 692:698 arg1 material 700:707 diamond is a hydrophobic support material 667:707 diamond is a hydrophobic support material 667:707 Poly(GMA/DVB) and cellulose represent hydrophilic supports whereas diamond is a hydrophobic support material. 28235995 4 10 dep hydrophilic 638:648 arg1 supports 650:657 supports 650:657 supports 650:657 Poly(GMA/DVB) and cellulose represent hydrophilic supports whereas diamond is a hydrophobic support material. 28235995 2 11 theme conventional 339:350 arg1 materials 360:368 conventional support materials 339:368 conventional support materials like silica and cellulose 339:394 A few hydrazide - functionalized materials with surface modification protocols compatible to conventional support materials like silica and cellulose are reported. 28235995 1 12 theme support 228:234 arg1 material 236:243 a suitable support material 217:243 a suitable support material 217:243 In affinity chromatography, enrichment of biomolecules is dependent on the selection of affinity sites immobilized onto a suitable support material. 28235995 5 13 theme reaction 790:797 arg1 completion 799:808 reaction completion 790:808 reaction completion 790:808 SEM images of three materials provide surface morphology whereas FT-IR confirms reaction completion and derivatization. 28235995 11 14 from density 1498:1504 arg1 poly 1520:1523 poly 1520:1523 poly(GMA/DVB) 1520:1532 The hydrazide group density on cellulose, poly(GMA/DVB), and diamond is 2.8, 2.3, and 2.1 mmol/g, respectively; this contributes towards the specificity and sensitivity of designed materials. 28235995 11 14 from density 1498:1504 arg1 cellulose 1509:1517 cellulose 1509:1517 cellulose 1509:1517 The hydrazide group density on cellulose, poly(GMA/DVB), and diamond is 2.8, 2.3, and 2.1 mmol/g, respectively; this contributes towards the specificity and sensitivity of designed materials. 28235995 11 14 from density 1498:1504 arg1 diamond 1539:1545 diamond 1539:1545 diamond 1539:1545 The hydrazide group density on cellulose, poly(GMA/DVB), and diamond is 2.8, 2.3, and 2.1 mmol/g, respectively; this contributes towards the specificity and sensitivity of designed materials. 28235995 11 14 from density 1498:1504 arg1 GMA/DVB 1525:1531 GMA/DVB 1525:1531 GMA/DVB 1525:1531 The hydrazide group density on cellulose, poly(GMA/DVB), and diamond is 2.8, 2.3, and 2.1 mmol/g, respectively; this contributes towards the specificity and sensitivity of designed materials. 28235995 14 15 theme Abstract 1978:1985 arg1 Glycopeptides 1987:1999 Graphical Abstract Glycopeptides 1968:1999 Graphical Abstract Glycopeptides 1968:1999 Graphical Abstract Glycopeptides enrichment by hydrazine affinity. 28235995 6 16 gly glycopeptides 906:918 arg2 glycopeptides 906:918 glycopeptides enrichment 906:929 glycopeptides enrichment 906:929 These hydrazide - functionalized materials are applied to fetuin digest for glycopeptides enrichment and subsequently for selectivity and sensitivity assessment. 28235995 9 17 theme 83 1333:1334 arg1 % 1342:1342 83 and 71% 1333:1342 % 1342:1342 Poly(GMA/DVB) shows recovery up to 89%, while recovery for cellulose and diamond is 83 and 71%, respectively. 28235995 9 18 dep 89 1284:1285 arg1 to 1281:1282 to 1281:1282 to 1281:1282 Poly(GMA/DVB) shows recovery up to 89%, while recovery for cellulose and diamond is 83 and 71%, respectively. 28235995 9 19 theme 71 1340:1341 arg1 % 1342:1342 83 and 71% 1333:1342 % 1342:1342 Poly(GMA/DVB) shows recovery up to 89%, while recovery for cellulose and diamond is 83 and 71%, respectively. 28235995 7 20 theme enrichment 1078:1087 arg1 experiments 1089:1099 the enrichment experiments 1074:1099 the enrichment experiments 1074:1099 Statistically, poly(GMA/DVB) shows 85.7% sensitivity with specificity of 88.8% in the enrichment experiments. 28235995 13 21 theme affinity 1923:1930 arg1 materials 1932:1940 affinity materials 1923:1940 affinity materials 1923:1940 Therefore this study provides routes for the economical surface modifications of support materials and to fabricate affinity materials with improved efficiency. 28235995 12 22 theme importance 1795:1804 arg1 glycoproteins 1769:1781 serum glycoproteins 1763:1781 serum glycoproteins of clinical importance 1763:1804 The materials are also applied to serum samples and enriched glycopeptides characteristic of serum glycoproteins of clinical importance. 28235995 7 23 from specificity 1050:1060 arg1 experiments 1089:1099 the enrichment experiments 1074:1099 the enrichment experiments 1074:1099 Statistically, poly(GMA/DVB) shows 85.7% sensitivity with specificity of 88.8% in the enrichment experiments. 28235995 9 24 dep % 1286:1286 arg1 89 1284:1285 89 1284:1285 89 1284:1285 Poly(GMA/DVB) shows recovery up to 89%, while recovery for cellulose and diamond is 83 and 71%, respectively. 28235995 2 25 theme functionalized 264:277 arg1 materials 279:287 functionalized materials 264:287 functionalized materials with surface modification protocols compatible to conventional support materials like silica and cellulose 264:394 A few hydrazide - functionalized materials with surface modification protocols compatible to conventional support materials like silica and cellulose are reported. 28235995 12 26 theme characteristic 1745:1758 arg1 samples 1710:1716 serum samples 1704:1716 serum samples 1704:1716 The materials are also applied to serum samples and enriched glycopeptides characteristic of serum glycoproteins of clinical importance. 28235995 12 27 gly glycoproteins 1769:1781 arg1 glycoproteins 1769:1781 serum glycoproteins 1763:1781 serum glycoproteins of clinical importance 1763:1804 The materials are also applied to serum samples and enriched glycopeptides characteristic of serum glycoproteins of clinical importance. 28235995 13 28 mod modifications 1871:1883 arg1 materials 1896:1904 support materials 1888:1904 support materials 1888:1904 Therefore this study provides routes for the economical surface modifications of support materials and to fabricate affinity materials with improved efficiency. 28235995 13 28 mod modifications 1871:1883 arg3 surface 1863:1869 the economical surface modifications 1848:1883 the economical surface modifications of support materials 1848:1904 Therefore this study provides routes for the economical surface modifications of support materials and to fabricate affinity materials with improved efficiency. 28235995 1 29 theme affinity 185:192 arg1 sites 194:198 affinity sites 185:198 affinity sites immobilized onto a suitable support material 185:243 In affinity chromatography, enrichment of biomolecules is dependent on the selection of affinity sites immobilized onto a suitable support material. 28235995 12 30 theme serum 1763:1767 arg1 glycoproteins 1769:1781 serum glycoproteins 1763:1781 serum glycoproteins of clinical importance 1763:1804 The materials are also applied to serum samples and enriched glycopeptides characteristic of serum glycoproteins of clinical importance. 28235995 8 31 gly glycopeptides 1186:1198 arg2 glycopeptides 1186:1198 glycopeptides 1186:1198 glycopeptides 1186:1198 Diamond offers hydrophobic interactions to non-glycopeptides and they co-elute with glycopeptides, resulting in reduced sensitivity down to 69.2%. 28235995 12 32 gly glycopeptides 1731:1743 arg2 glycopeptides 1731:1743 enriched glycopeptides 1722:1743 enriched glycopeptides 1722:1743 The materials are also applied to serum samples and enriched glycopeptides characteristic of serum glycoproteins of clinical importance. 28235995 1 33 from dependent 155:163 arg1 chromatography 109:122 affinity chromatography 100:122 affinity chromatography 100:122 In affinity chromatography, enrichment of biomolecules is dependent on the selection of affinity sites immobilized onto a suitable support material. 28235995 1 34 theme affinity 100:107 arg1 chromatography 109:122 affinity chromatography 100:122 affinity chromatography 100:122 In affinity chromatography, enrichment of biomolecules is dependent on the selection of affinity sites immobilized onto a suitable support material. 28235995 12 35 theme enriched 1722:1729 arg1 glycopeptides 1731:1743 enriched glycopeptides 1722:1743 enriched glycopeptides 1722:1743 The materials are also applied to serum samples and enriched glycopeptides characteristic of serum glycoproteins of clinical importance. 28235995 3 36 theme modification/derivatization 437:463 arg1 pathways 465:472 the modification/derivatization pathways 433:472 the modification/derivatization pathways that can be adopted to modify the support materials with similar surface chemistry like cellulose, poly(GMA/DVB), or diamond 433:597 The study demonstrates the modification/derivatization pathways that can be adopted to modify the support materials with similar surface chemistry like cellulose, poly(GMA/DVB), or diamond. 28235995 0 37 theme Hydrazide-functionalized 0:23 arg1 affinity 25:32 Hydrazide-functionalized affinity 0:32 Hydrazide-functionalized affinity on conventional 0:48 Hydrazide-functionalized affinity on conventional support materials for glycopeptide enrichment. 28235995 7 38 theme 85.7 1027:1030 arg1 % 1031:1031 % 1031:1031 % 1031:1031 Statistically, poly(GMA/DVB) shows 85.7% sensitivity with specificity of 88.8% in the enrichment experiments. 28235995 10 39 from digest 1428:1433 arg1 peptide 1407:1413 mono-N-linked-glycosylated peptide 1380:1413 mono-N-linked-glycosylated peptide from tryptic digest of chicken avidin spiked in fetuin digest 1380:1475 The materials enrich mono-N-linked-glycosylated peptide from tryptic digest of chicken avidin spiked in fetuin digest. 28235995 6 40 theme fetuin 888:893 arg1 digest 895:900 fetuin digest 888:900 fetuin digest for glycopeptides enrichment and subsequently for selectivity and sensitivity assessment 888:989 These hydrazide - functionalized materials are applied to fetuin digest for glycopeptides enrichment and subsequently for selectivity and sensitivity assessment. 28235995 10 41 theme mono-N-linked-glycosylated 1380:1405 arg1 peptide 1407:1413 mono-N-linked-glycosylated peptide 1380:1413 mono-N-linked-glycosylated peptide from tryptic digest of chicken avidin spiked in fetuin digest 1380:1475 The materials enrich mono-N-linked-glycosylated peptide from tryptic digest of chicken avidin spiked in fetuin digest. 28235995 3 42 theme similar 531:537 arg1 chemistry 547:555 similar surface chemistry 531:555 similar surface chemistry 531:555 The study demonstrates the modification/derivatization pathways that can be adopted to modify the support materials with similar surface chemistry like cellulose, poly(GMA/DVB), or diamond. 28235995 6 43 dep selectivity 952:962 arg1 assessment 980:989 assessment 980:989 assessment 980:989 These hydrazide - functionalized materials are applied to fetuin digest for glycopeptides enrichment and subsequently for selectivity and sensitivity assessment. 28235995 11 44 theme designed 1650:1657 arg1 materials 1659:1667 designed materials 1650:1667 designed materials 1650:1667 The hydrazide group density on cellulose, poly(GMA/DVB), and diamond is 2.8, 2.3, and 2.1 mmol/g, respectively; this contributes towards the specificity and sensitivity of designed materials. 28235995 13 45 theme support 1888:1894 arg1 materials 1896:1904 support materials 1888:1904 support materials 1888:1904 Therefore this study provides routes for the economical surface modifications of support materials and to fabricate affinity materials with improved efficiency. 28235995 0 46 gly glycopeptide 72:83 arg2 glycopeptide 72:83 glycopeptide enrichment 72:94 glycopeptide enrichment 72:94 Hydrazide-functionalized affinity on conventional support materials for glycopeptide enrichment. 28235995 4 47 theme diamond 667:673 arg1 material 700:707 diamond is a hydrophobic support material 667:707 diamond is a hydrophobic support material 667:707 Poly(GMA/DVB) and cellulose represent hydrophilic supports whereas diamond is a hydrophobic support material. 28235995 5 48 theme SEM 710:712 arg1 images 714:719 SEM images 710:719 SEM images of three materials 710:738 SEM images of three materials provide surface morphology whereas FT-IR confirms reaction completion and derivatization. 28235995 10 49 theme chicken 1438:1444 arg1 avidin 1446:1451 chicken avidin 1438:1451 chicken avidin 1438:1451 The materials enrich mono-N-linked-glycosylated peptide from tryptic digest of chicken avidin spiked in fetuin digest. 28235995 13 50 theme economical 1852:1861 arg1 modifications 1871:1883 the economical surface modifications 1848:1883 the economical surface modifications of support materials 1848:1904 Therefore this study provides routes for the economical surface modifications of support materials and to fabricate affinity materials with improved efficiency. 28235995 11 51 theme hydrazide 1482:1490 arg1 2.8 1550:1552 2.8 1550:1552 2.8 1550:1552 The hydrazide group density on cellulose, poly(GMA/DVB), and diamond is 2.8, 2.3, and 2.1 mmol/g, respectively; this contributes towards the specificity and sensitivity of designed materials. 28235995 11 51 theme hydrazide 1482:1490 arg1 density 1498:1504 The hydrazide group density 1478:1504 The hydrazide group density on cellulose, poly(GMA/DVB), and diamond 1478:1545 The hydrazide group density on cellulose, poly(GMA/DVB), and diamond is 2.8, 2.3, and 2.1 mmol/g, respectively; this contributes towards the specificity and sensitivity of designed materials. 28235995 10 52 theme fetuin 1463:1468 arg1 digest 1470:1475 fetuin digest 1463:1475 fetuin digest 1463:1475 The materials enrich mono-N-linked-glycosylated peptide from tryptic digest of chicken avidin spiked in fetuin digest. 28235995 1 53 theme sites 194:198 arg1 selection 172:180 the selection 168:180 the selection of affinity sites immobilized onto a suitable support material 168:243 In affinity chromatography, enrichment of biomolecules is dependent on the selection of affinity sites immobilized onto a suitable support material. 28235995 8 54 theme hydrophobic 1117:1127 arg1 interactions 1129:1140 hydrophobic interactions 1117:1140 hydrophobic interactions to non-glycopeptides 1117:1161 Diamond offers hydrophobic interactions to non-glycopeptides and they co-elute with glycopeptides, resulting in reduced sensitivity down to 69.2%. 28235995 7 55 from experiments 1089:1099 arg1 specificity 1050:1060 specificity 1050:1060 specificity of 88.8% in the enrichment experiments 1050:1099 Statistically, poly(GMA/DVB) shows 85.7% sensitivity with specificity of 88.8% in the enrichment experiments. 28235995 3 56 with materials 516:524 arg1 chemistry 547:555 similar surface chemistry 531:555 similar surface chemistry 531:555 The study demonstrates the modification/derivatization pathways that can be adopted to modify the support materials with similar surface chemistry like cellulose, poly(GMA/DVB), or diamond. 28235995 2 57 theme support 352:358 arg1 materials 360:368 conventional support materials 339:368 conventional support materials like silica and cellulose 339:394 A few hydrazide - functionalized materials with surface modification protocols compatible to conventional support materials like silica and cellulose are reported. 28235995 1 58 theme suitable 219:226 arg1 material 236:243 a suitable support material 217:243 a suitable support material 217:243 In affinity chromatography, enrichment of biomolecules is dependent on the selection of affinity sites immobilized onto a suitable support material. 28235995 6 59 theme hydrazide 836:844 arg1 materials 863:871 These hydrazide - functionalized materials 830:871 materials 863:871 These hydrazide - functionalized materials are applied to fetuin digest for glycopeptides enrichment and subsequently for selectivity and sensitivity assessment. 28235995 4 60 theme hydrophobic 680:690 arg1 material 700:707 diamond is a hydrophobic support material 667:707 diamond is a hydrophobic support material 667:707 Poly(GMA/DVB) and cellulose represent hydrophilic supports whereas diamond is a hydrophobic support material. 28235995 2 61 with materials 279:287 arg1 protocols 315:323 surface modification protocols 294:323 surface modification protocols compatible to conventional support materials like silica and cellulose 294:394 A few hydrazide - functionalized materials with surface modification protocols compatible to conventional support materials like silica and cellulose are reported. 28235995 5 62 theme materials 730:738 arg1 images 714:719 SEM images 710:719 SEM images of three materials 710:738 SEM images of three materials provide surface morphology whereas FT-IR confirms reaction completion and derivatization. 28235995 2 63 theme few 248:250 arg1 hydrazide 252:260 A few hydrazide 246:260 A few hydrazide 246:260 A few hydrazide - functionalized materials with surface modification protocols compatible to conventional support materials like silica and cellulose are reported. 28235995 1 64 theme biomolecules 139:150 arg1 enrichment 125:134 enrichment 125:134 enrichment of biomolecules 125:150 In affinity chromatography, enrichment of biomolecules is dependent on the selection of affinity sites immobilized onto a suitable support material. 28235995 5 65 theme surface 748:754 arg1 morphology 756:765 surface morphology 748:765 surface morphology 748:765 SEM images of three materials provide surface morphology whereas FT-IR confirms reaction completion and derivatization. 28235995 2 66 theme surface 294:300 arg1 protocols 315:323 surface modification protocols 294:323 surface modification protocols compatible to conventional support materials like silica and cellulose 294:394 A few hydrazide - functionalized materials with surface modification protocols compatible to conventional support materials like silica and cellulose are reported. 28235995 12 67 theme glycoproteins 1769:1781 arg1 characteristic 1745:1758 characteristic 1745:1758 characteristic 1745:1758 The materials are also applied to serum samples and enriched glycopeptides characteristic of serum glycoproteins of clinical importance. 28235995 8 68 gly non-glycopeptides 1145:1161 arg2 non-glycopeptides 1145:1161 non-glycopeptides 1145:1161 non-glycopeptides 1145:1161 Diamond offers hydrophobic interactions to non-glycopeptides and they co-elute with glycopeptides, resulting in reduced sensitivity down to 69.2%. 28235995 12 69 theme clinical 1786:1793 arg1 importance 1795:1804 clinical importance 1786:1804 clinical importance 1786:1804 The materials are also applied to serum samples and enriched glycopeptides characteristic of serum glycoproteins of clinical importance. 28235995 0 70 from affinity 25:32 arg1 conventional 37:48 conventional 37:48 conventional 37:48 Hydrazide-functionalized affinity on conventional support materials for glycopeptide enrichment. 28235995 7 71 from % 1069:1069 arg1 experiments 1089:1099 the enrichment experiments 1074:1099 the enrichment experiments 1074:1099 Statistically, poly(GMA/DVB) shows 85.7% sensitivity with specificity of 88.8% in the enrichment experiments. 28235995 7 72 theme % 1069:1069 arg1 specificity 1050:1060 specificity 1050:1060 specificity of 88.8% in the enrichment experiments 1050:1099 Statistically, poly(GMA/DVB) shows 85.7% sensitivity with specificity of 88.8% in the enrichment experiments. 28235995 13 73 theme improved 1947:1954 arg1 efficiency 1956:1965 improved efficiency 1947:1965 improved efficiency 1947:1965 Therefore this study provides routes for the economical surface modifications of support materials and to fabricate affinity materials with improved efficiency. 28235995 12 74 theme serum 1704:1708 arg1 samples 1710:1716 serum samples 1704:1716 serum samples 1704:1716 The materials are also applied to serum samples and enriched glycopeptides characteristic of serum glycoproteins of clinical importance. 28235995 5 75 dep provide 740:746 arg1 confirms 781:788 confirms 781:788 confirms reaction completion and derivatization 781:827 SEM images of three materials provide surface morphology whereas FT-IR confirms reaction completion and derivatization. 28235995 5 75 dep provide 740:746 arg1 whereas 767:773 whereas 767:773 whereas 767:773 SEM images of three materials provide surface morphology whereas FT-IR confirms reaction completion and derivatization. 28235995 3 76 theme support 508:514 arg1 materials 516:524 the support materials 504:524 the support materials with similar surface chemistry like cellulose, poly(GMA/DVB), or diamond 504:597 The study demonstrates the modification/derivatization pathways that can be adopted to modify the support materials with similar surface chemistry like cellulose, poly(GMA/DVB), or diamond. 28235995 7 77 theme % 1031:1031 arg1 sensitivity 1033:1043 85.7% sensitivity 1027:1043 85.7% sensitivity 1027:1043 Statistically, poly(GMA/DVB) shows 85.7% sensitivity with specificity of 88.8% in the enrichment experiments. 28235995 9 78 dep recovery 1269:1276 arg1 % 1286:1286 % 1286:1286 % 1286:1286 Poly(GMA/DVB) shows recovery up to 89%, while recovery for cellulose and diamond is 83 and 71%, respectively. 28235995 3 79 theme surface 539:545 arg1 chemistry 547:555 similar surface chemistry 531:555 similar surface chemistry 531:555 The study demonstrates the modification/derivatization pathways that can be adopted to modify the support materials with similar surface chemistry like cellulose, poly(GMA/DVB), or diamond. 28235995 8 80 theme reduced 1214:1220 arg1 sensitivity 1222:1232 reduced sensitivity 1214:1232 reduced sensitivity down to 69.2% 1214:1246 Diamond offers hydrophobic interactions to non-glycopeptides and they co-elute with glycopeptides, resulting in reduced sensitivity down to 69.2%. 28235995 6 81 theme functionalized 848:861 arg1 materials 863:871 These hydrazide - functionalized materials 830:871 materials 863:871 These hydrazide - functionalized materials are applied to fetuin digest for glycopeptides enrichment and subsequently for selectivity and sensitivity assessment. 28235995 0 82 theme glycopeptide 72:83 arg1 enrichment 85:94 glycopeptide enrichment 72:94 glycopeptide enrichment 72:94 Hydrazide-functionalized affinity on conventional support materials for glycopeptide enrichment. 28235995 10 83 theme tryptic 1420:1426 arg1 digest 1428:1433 tryptic digest 1420:1433 tryptic digest of chicken avidin spiked in fetuin digest 1420:1475 The materials enrich mono-N-linked-glycosylated peptide from tryptic digest of chicken avidin spiked in fetuin digest. 28235995 11 84 theme materials 1659:1667 arg1 sensitivity 1635:1645 sensitivity 1635:1645 sensitivity 1635:1645 The hydrazide group density on cellulose, poly(GMA/DVB), and diamond is 2.8, 2.3, and 2.1 mmol/g, respectively; this contributes towards the specificity and sensitivity of designed materials. 28235995 11 84 theme materials 1659:1667 arg1 specificity 1619:1629 specificity 1619:1629 specificity 1619:1629 The hydrazide group density on cellulose, poly(GMA/DVB), and diamond is 2.8, 2.3, and 2.1 mmol/g, respectively; this contributes towards the specificity and sensitivity of designed materials. 28235995 1 85 from chromatography 109:122 arg1 dependent 155:163 dependent 155:163 dependent 155:163 In affinity chromatography, enrichment of biomolecules is dependent on the selection of affinity sites immobilized onto a suitable support material. 28235995 13 86 theme materials 1896:1904 arg1 modifications 1871:1883 the economical surface modifications 1848:1883 the economical surface modifications of support materials 1848:1904 Therefore this study provides routes for the economical surface modifications of support materials and to fabricate affinity materials with improved efficiency. 28235995 10 87 theme avidin 1446:1451 arg1 digest 1428:1433 tryptic digest 1420:1433 tryptic digest of chicken avidin spiked in fetuin digest 1420:1475 The materials enrich mono-N-linked-glycosylated peptide from tryptic digest of chicken avidin spiked in fetuin digest. 27195445 11 0 theme infected 1440:1447 arg1 cells 1449:1453 reactivated latently infected cells 1419:1453 reactivated latently infected cells 1419:1453 The changed proteins suggest that cell migration, response to wounding and immune response might be impaired in reactivated latently infected cells. 27195445 12 1 from mechanisms 1537:1546 arg1 pathogenesis 1555:1566 HIV pathogenesis 1551:1566 HIV pathogenesis 1551:1566 Glycoproteomics merits future application using primary cells to discover reveal mechanisms in HIV pathogenesis. 27195445 4 2 from lines 530:534 arg1 different 502:510 different 502:510 different 502:510 This finding suggests that glyco-phenotype might be different in these two cell lines. 27195445 8 3 theme Quantitative 866:877 arg1 analysis 888:895 Quantitative LC-MS/MS analysis 866:895 Quantitative LC-MS/MS analysis 866:895 Quantitative LC-MS/MS analysis revealed a change of 236 glycosite-containing peptides from 172 glycoproteins between the two cell lines without reactivation. 27195445 0 4 theme quantitative 82:93 arg1 glycoproteomics 95:109 quantitative glycoproteomics 82:109 quantitative glycoproteomics 82:109 Identification of glycoproteins associated with HIV latently infected cells using quantitative glycoproteomics. 27195445 12 5 theme HIV 1551:1553 arg1 pathogenesis 1555:1566 HIV pathogenesis 1551:1566 HIV pathogenesis 1551:1566 Glycoproteomics merits future application using primary cells to discover reveal mechanisms in HIV pathogenesis. 27195445 10 6 located observed 1278:1285 arg1 lines 1300:1304 both cell lines 1290:1304 both cell lines 1290:1304 After reactivation of latency, changes in glycosite-containing peptides were observed in both cell lines. 27195445 10 6 located observed 1278:1285 arg2 changes 1232:1238 changes 1232:1238 changes in glycosite-containing peptides 1232:1271 After reactivation of latency, changes in glycosite-containing peptides were observed in both cell lines. 27195445 4 7 theme cell 525:528 arg1 lines 530:534 these two cell lines 515:534 these two cell lines 515:534 This finding suggests that glyco-phenotype might be different in these two cell lines. 27195445 9 8 gly glycoprotein 1093:1104 arg1 glycoprotein 1093:1104 glycoprotein metabolic process 1093:1122 glycoprotein metabolic process 1093:1122 Bioinformatic analysis suggests that cell adhesion, immune response, glycoprotein metabolic process, cell motion, and cell activation were associated with the changed proteins. 27195445 0 9 gly glycoproteins 18:30 arg1 glycoproteins 18:30 glycoproteins 18:30 glycoproteins 18:30 Identification of glycoproteins associated with HIV latently infected cells using quantitative glycoproteomics. 27195445 12 10 theme future 1479:1484 arg1 application 1486:1496 future application 1479:1496 future application using primary cells to discover reveal mechanisms in HIV pathogenesis 1479:1566 Glycoproteomics merits future application using primary cells to discover reveal mechanisms in HIV pathogenesis. 27195445 9 11 theme cell 1125:1128 arg1 motion 1130:1135 cell motion 1125:1135 cell motion 1125:1135 Bioinformatic analysis suggests that cell adhesion, immune response, glycoprotein metabolic process, cell motion, and cell activation were associated with the changed proteins. 27195445 3 12 theme HIV 378:380 arg1 cells 406:410 HIV latently infected ACH-2 cells 378:410 HIV latently infected ACH-2 cells 378:410 We have recently reported that glycoproteins were differentially secreted from HIV latently infected ACH-2 cells compared to the parental A3.01 cells. 27195445 2 13 theme Compelling 163:172 arg1 reports 174:180 Compelling reports 163:180 Compelling reports 163:180 Compelling reports suggest that there is a distinct profile of surface proteins that can be used for targeting latently infected cells. 27195445 11 14 theme cell 1341:1344 arg1 migration 1346:1354 cell migration 1341:1354 cell migration 1341:1354 The changed proteins suggest that cell migration, response to wounding and immune response might be impaired in reactivated latently infected cells. 27195445 2 15 theme infected 283:290 arg1 cells 292:296 latently infected cells 274:296 latently infected cells 274:296 Compelling reports suggest that there is a distinct profile of surface proteins that can be used for targeting latently infected cells. 27195445 9 16 theme metabolic 1106:1114 arg1 process 1116:1122 glycoprotein metabolic process 1093:1122 glycoprotein metabolic process 1093:1122 Bioinformatic analysis suggests that cell adhesion, immune response, glycoprotein metabolic process, cell motion, and cell activation were associated with the changed proteins. 27195445 12 17 theme primary 1504:1510 arg1 cells 1512:1516 primary cells 1504:1516 primary cells 1504:1516 Glycoproteomics merits future application using primary cells to discover reveal mechanisms in HIV pathogenesis. 27195445 5 18 theme glycoproteomic 617:630 arg1 analysis 632:639 a glycoproteomic analysis 615:639 a glycoproteomic analysis 615:639 To determine the difference, the ACH-2 and A3.01 cell lines were subjected to a glycoproteomic analysis. 27195445 9 19 theme glycoprotein 1093:1104 arg1 process 1116:1122 glycoprotein metabolic process 1093:1122 glycoprotein metabolic process 1093:1122 Bioinformatic analysis suggests that cell adhesion, immune response, glycoprotein metabolic process, cell motion, and cell activation were associated with the changed proteins. 27195445 4 20 from different 502:510 arg1 lines 530:534 these two cell lines 515:534 these two cell lines 515:534 This finding suggests that glyco-phenotype might be different in these two cell lines. 27195445 6 21 from glycoproteins 719:731 arg1 number 650:655 A total number 642:655 A total number of 940 unique N-linked glycosite-containing peptides from 515 glycoproteins 642:731 A total number of 940 unique N-linked glycosite-containing peptides from 515 glycoproteins were identified. 27195445 6 21 from glycoproteins 719:731 arg1 peptides 701:708 940 unique N-linked glycosite-containing peptides 660:708 940 unique N-linked glycosite-containing peptides from 515 glycoproteins 660:731 A total number of 940 unique N-linked glycosite-containing peptides from 515 glycoproteins were identified. 27195445 2 22 used used 255:258 arg2 profile 215:221 a distinct profile 204:221 a distinct profile of surface proteins that can be used for targeting latently infected cells 204:296 Compelling reports suggest that there is a distinct profile of surface proteins that can be used for targeting latently infected cells. 27195445 3 23 theme ACH-2 400:404 arg1 cells 406:410 HIV latently infected ACH-2 cells 378:410 HIV latently infected ACH-2 cells 378:410 We have recently reported that glycoproteins were differentially secreted from HIV latently infected ACH-2 cells compared to the parental A3.01 cells. 27195445 5 24 theme A3.01 580:584 arg1 lines 591:595 the ACH-2 and A3.01 cell lines 566:595 lines 591:595 To determine the difference, the ACH-2 and A3.01 cell lines were subjected to a glycoproteomic analysis. 27195445 9 25 theme cell 1142:1145 arg1 activation 1147:1156 cell activation 1142:1156 cell activation 1142:1156 Bioinformatic analysis suggests that cell adhesion, immune response, glycoprotein metabolic process, cell motion, and cell activation were associated with the changed proteins. 27195445 3 26 theme A3.01 437:441 arg1 cells 443:447 the parental A3.01 cells 424:447 the parental A3.01 cells 424:447 We have recently reported that glycoproteins were differentially secreted from HIV latently infected ACH-2 cells compared to the parental A3.01 cells. 27195445 9 27 theme Bioinformatic 1024:1036 arg1 analysis 1038:1045 Bioinformatic analysis 1024:1045 Bioinformatic analysis 1024:1045 Bioinformatic analysis suggests that cell adhesion, immune response, glycoprotein metabolic process, cell motion, and cell activation were associated with the changed proteins. 27195445 5 28 theme cell 586:589 arg1 lines 591:595 the ACH-2 and A3.01 cell lines 566:595 lines 591:595 To determine the difference, the ACH-2 and A3.01 cell lines were subjected to a glycoproteomic analysis. 27195445 1 29 theme HIV 112:114 arg1 infection 116:124 HIV infection 112:124 HIV infection 112:124 HIV infection is not curable due to viral latency. 27195445 6 30 theme peptides 701:708 arg1 number 650:655 A total number 642:655 A total number of 940 unique N-linked glycosite-containing peptides from 515 glycoproteins 642:731 A total number of 940 unique N-linked glycosite-containing peptides from 515 glycoproteins were identified. 27195445 8 31 from glycoproteins 961:973 arg1 peptides 943:950 236 glycosite-containing peptides 918:950 236 glycosite-containing peptides from 172 glycoproteins 918:973 Quantitative LC-MS/MS analysis revealed a change of 236 glycosite-containing peptides from 172 glycoproteins between the two cell lines without reactivation. 27195445 8 31 from glycoproteins 961:973 arg1 change 908:913 a change 906:913 a change of 236 glycosite-containing peptides from 172 glycoproteins between the two cell lines without reactivation 906:1021 Quantitative LC-MS/MS analysis revealed a change of 236 glycosite-containing peptides from 172 glycoproteins between the two cell lines without reactivation. 27195445 11 32 theme immune 1382:1387 arg1 response 1389:1396 immune response 1382:1396 immune response 1382:1396 The changed proteins suggest that cell migration, response to wounding and immune response might be impaired in reactivated latently infected cells. 27195445 7 33 theme membrane-associated 822:840 arg1 proteins 842:849 membrane-associated proteins 822:849 membrane-associated proteins 822:849 Among the glycoproteins, 365 and 104 were annotated as cell surface and membrane-associated proteins, respectively. 27195445 7 33 theme membrane-associated 822:840 arg1 365 775:777 365 775:777 365 775:777 Among the glycoproteins, 365 and 104 were annotated as cell surface and membrane-associated proteins, respectively. 27195445 7 33 theme membrane-associated 822:840 arg1 104 783:785 104 783:785 104 783:785 Among the glycoproteins, 365 and 104 were annotated as cell surface and membrane-associated proteins, respectively. 27195445 10 34 from changes 1232:1238 arg1 peptides 1264:1271 glycosite-containing peptides 1243:1271 glycosite-containing peptides 1243:1271 After reactivation of latency, changes in glycosite-containing peptides were observed in both cell lines. 27195445 7 35 gly glycoproteins 760:772 arg1 glycoproteins 760:772 the glycoproteins 756:772 the glycoproteins 756:772 Among the glycoproteins, 365 and 104 were annotated as cell surface and membrane-associated proteins, respectively. 27195445 12 36 theme Glycoproteomics 1456:1470 arg1 merits 1472:1477 Glycoproteomics merits 1456:1477 Glycoproteomics merits 1456:1477 Glycoproteomics merits future application using primary cells to discover reveal mechanisms in HIV pathogenesis. 27195445 6 37 theme glycosite-containing 680:699 arg1 peptides 701:708 940 unique N-linked glycosite-containing peptides 660:708 940 unique N-linked glycosite-containing peptides from 515 glycoproteins 660:731 A total number of 940 unique N-linked glycosite-containing peptides from 515 glycoproteins were identified. 27195445 3 38 theme infected 391:398 arg1 cells 406:410 HIV latently infected ACH-2 cells 378:410 HIV latently infected ACH-2 cells 378:410 We have recently reported that glycoproteins were differentially secreted from HIV latently infected ACH-2 cells compared to the parental A3.01 cells. 27195445 7 39 theme cell 805:808 arg1 surface 810:816 cell surface 805:816 cell surface 805:816 Among the glycoproteins, 365 and 104 were annotated as cell surface and membrane-associated proteins, respectively. 27195445 7 39 theme cell 805:808 arg1 104 783:785 104 783:785 104 783:785 Among the glycoproteins, 365 and 104 were annotated as cell surface and membrane-associated proteins, respectively. 27195445 7 39 theme cell 805:808 arg1 365 775:777 365 775:777 365 775:777 Among the glycoproteins, 365 and 104 were annotated as cell surface and membrane-associated proteins, respectively. 27195445 6 40 theme N-linked 671:678 arg1 peptides 701:708 940 unique N-linked glycosite-containing peptides 660:708 940 unique N-linked glycosite-containing peptides from 515 glycoproteins 660:731 A total number of 940 unique N-linked glycosite-containing peptides from 515 glycoproteins were identified. 27195445 8 41 theme peptides 943:950 arg1 change 908:913 a change 906:913 a change of 236 glycosite-containing peptides from 172 glycoproteins between the two cell lines without reactivation 906:1021 Quantitative LC-MS/MS analysis revealed a change of 236 glycosite-containing peptides from 172 glycoproteins between the two cell lines without reactivation. 27195445 0 42 theme HIV 48:50 arg1 cells 70:74 HIV latently infected cells 48:74 HIV latently infected cells using quantitative glycoproteomics 48:109 Identification of glycoproteins associated with HIV latently infected cells using quantitative glycoproteomics. 27195445 8 43 from change 908:913 arg1 glycoproteins 961:973 172 glycoproteins 957:973 172 glycoproteins 957:973 Quantitative LC-MS/MS analysis revealed a change of 236 glycosite-containing peptides from 172 glycoproteins between the two cell lines without reactivation. 27195445 6 44 from number 650:655 arg1 glycoproteins 719:731 515 glycoproteins 715:731 515 glycoproteins 715:731 A total number of 940 unique N-linked glycosite-containing peptides from 515 glycoproteins were identified. 27195445 6 45 theme unique 664:669 arg1 peptides 701:708 940 unique N-linked glycosite-containing peptides 660:708 940 unique N-linked glycosite-containing peptides from 515 glycoproteins 660:731 A total number of 940 unique N-linked glycosite-containing peptides from 515 glycoproteins were identified. 27195445 3 46 theme parental 428:435 arg1 cells 443:447 the parental A3.01 cells 424:447 the parental A3.01 cells 424:447 We have recently reported that glycoproteins were differentially secreted from HIV latently infected ACH-2 cells compared to the parental A3.01 cells. 27195445 10 47 theme latency 1223:1229 arg1 reactivation 1207:1218 reactivation 1207:1218 reactivation of latency 1207:1229 After reactivation of latency, changes in glycosite-containing peptides were observed in both cell lines. 27195445 9 48 theme cell 1061:1064 arg1 adhesion 1066:1073 cell adhesion 1061:1073 cell adhesion 1061:1073 Bioinformatic analysis suggests that cell adhesion, immune response, glycoprotein metabolic process, cell motion, and cell activation were associated with the changed proteins. 27195445 2 49 theme proteins 234:241 arg1 profile 215:221 a distinct profile 204:221 a distinct profile of surface proteins that can be used for targeting latently infected cells 204:296 Compelling reports suggest that there is a distinct profile of surface proteins that can be used for targeting latently infected cells. 27195445 0 50 theme infected 61:68 arg1 cells 70:74 HIV latently infected cells 48:74 HIV latently infected cells using quantitative glycoproteomics 48:109 Identification of glycoproteins associated with HIV latently infected cells using quantitative glycoproteomics. 27195445 6 51 link N-linked 671:678 arg1 peptides 701:708 940 unique N-linked glycosite-containing peptides 660:708 940 unique N-linked glycosite-containing peptides from 515 glycoproteins 660:731 A total number of 940 unique N-linked glycosite-containing peptides from 515 glycoproteins were identified. 27195445 2 52 theme surface 226:232 arg1 proteins 234:241 surface proteins 226:241 surface proteins 226:241 Compelling reports suggest that there is a distinct profile of surface proteins that can be used for targeting latently infected cells. 27195445 9 53 theme changed 1183:1189 arg1 proteins 1191:1198 the changed proteins 1179:1198 the changed proteins 1179:1198 Bioinformatic analysis suggests that cell adhesion, immune response, glycoprotein metabolic process, cell motion, and cell activation were associated with the changed proteins. 27195445 3 54 gly glycoproteins 330:342 arg1 glycoproteins 330:342 glycoproteins 330:342 glycoproteins 330:342 We have recently reported that glycoproteins were differentially secreted from HIV latently infected ACH-2 cells compared to the parental A3.01 cells. 27195445 6 55 gly glycoproteins 719:731 arg1 glycoproteins 719:731 515 glycoproteins 715:731 515 glycoproteins 715:731 A total number of 940 unique N-linked glycosite-containing peptides from 515 glycoproteins were identified. 27195445 9 56 theme immune 1076:1081 arg1 response 1083:1090 immune response 1076:1090 immune response 1076:1090 Bioinformatic analysis suggests that cell adhesion, immune response, glycoprotein metabolic process, cell motion, and cell activation were associated with the changed proteins. 27195445 2 57 theme distinct 206:213 arg1 profile 215:221 a distinct profile 204:221 a distinct profile of surface proteins that can be used for targeting latently infected cells 204:296 Compelling reports suggest that there is a distinct profile of surface proteins that can be used for targeting latently infected cells. 27195445 11 58 theme reactivated 1419:1429 arg1 cells 1449:1453 reactivated latently infected cells 1419:1453 reactivated latently infected cells 1419:1453 The changed proteins suggest that cell migration, response to wounding and immune response might be impaired in reactivated latently infected cells. 27195445 10 59 theme glycosite-containing 1243:1262 arg1 peptides 1264:1271 glycosite-containing peptides 1243:1271 glycosite-containing peptides 1243:1271 After reactivation of latency, changes in glycosite-containing peptides were observed in both cell lines. 27195445 11 60 theme changed 1311:1317 arg1 proteins 1319:1326 The changed proteins 1307:1326 The changed proteins 1307:1326 The changed proteins suggest that cell migration, response to wounding and immune response might be impaired in reactivated latently infected cells. 27195445 8 61 theme glycosite-containing 922:941 arg1 peptides 943:950 236 glycosite-containing peptides 918:950 236 glycosite-containing peptides from 172 glycoproteins 918:973 Quantitative LC-MS/MS analysis revealed a change of 236 glycosite-containing peptides from 172 glycoproteins between the two cell lines without reactivation. 27195445 10 62 theme cell 1295:1298 arg1 lines 1300:1304 both cell lines 1290:1304 both cell lines 1290:1304 After reactivation of latency, changes in glycosite-containing peptides were observed in both cell lines. 27195445 8 63 gly glycoproteins 961:973 arg1 glycoproteins 961:973 172 glycoproteins 957:973 172 glycoproteins 957:973 Quantitative LC-MS/MS analysis revealed a change of 236 glycosite-containing peptides from 172 glycoproteins between the two cell lines without reactivation. 27195445 8 64 theme cell 991:994 arg1 lines 996:1000 the two cell lines 983:1000 the two cell lines without reactivation 983:1021 Quantitative LC-MS/MS analysis revealed a change of 236 glycosite-containing peptides from 172 glycoproteins between the two cell lines without reactivation. 27195445 1 65 theme viral 148:152 arg1 latency 154:160 viral latency 148:160 viral latency 148:160 HIV infection is not curable due to viral latency. 27195445 6 66 theme total 644:648 arg1 number 650:655 A total number 642:655 A total number of 940 unique N-linked glycosite-containing peptides from 515 glycoproteins 642:731 A total number of 940 unique N-linked glycosite-containing peptides from 515 glycoproteins were identified. 27195445 0 67 theme glycoproteins 18:30 arg1 Identification 0:13 Identification 0:13 Identification of glycoproteins 0:30 Identification of glycoproteins associated with HIV latently infected cells using quantitative glycoproteomics. 27195445 12 68 dep application 1486:1496 arg1 merits 1472:1477 Glycoproteomics merits 1456:1477 Glycoproteomics merits 1456:1477 Glycoproteomics merits future application using primary cells to discover reveal mechanisms in HIV pathogenesis. 27195445 8 69 theme LC-MS/MS 879:886 arg1 analysis 888:895 Quantitative LC-MS/MS analysis 866:895 Quantitative LC-MS/MS analysis 866:895 Quantitative LC-MS/MS analysis revealed a change of 236 glycosite-containing peptides from 172 glycoproteins between the two cell lines without reactivation. 25810266 8 0 from changes 1427:1433 arg1 subunit 1454:1460 the integrin α3 subunit 1438:1460 the integrin α3 subunit 1438:1460 These findings highlight that single amino acid changes in the integrin α3 subunit may crucially alter the structure and complex processing of this integrin, completely preventing its functionality. 25810266 6 1 link N-linked 1062:1069 arg1 oligosaccharides 1071:1086 N-linked oligosaccharides 1062:1086 N-linked oligosaccharides 1062:1086 We show that the mutation altered the conformation of the extracellular β-propeller domain of the integrin α3 subunit preventing correct processing of N-linked oligosaccharides, heterodimerization with β1 integrin and maturation through cleavage into heavy and light chains in the Golgi. 25810266 3 2 theme acid 557:560 arg1 substitution 562:573 the single amino acid substitution 540:573 the single amino acid substitution 540:573 Here, we uncovered the disease-causing role and the molecular mechanisms underlying a homozygous ITGA3 mutation leading to the single amino acid substitution, p.R463W. 25810266 3 2 theme acid 557:560 arg1 p.R463W 576:582 p.R463W 576:582 p.R463W 576:582 Here, we uncovered the disease-causing role and the molecular mechanisms underlying a homozygous ITGA3 mutation leading to the single amino acid substitution, p.R463W. 25810266 5 3 theme direct 860:865 arg1 assessment 867:876 the direct assessment 856:876 the direct assessment of the authentic mutant protein 856:908 Although there was no clinical evidence for cutaneous fragility, the analysis of a skin sample and of skin epithelial cells enabled the direct assessment of the authentic mutant protein. 25810266 7 4 from present 1300:1306 arg1 adhesions 1317:1325 focal adhesions 1311:1325 focal adhesions 1311:1325 Confocal microscopy demonstrated that the mutant protein accumulated intracellularly, but it was not present in focal adhesions or on the cell membrane as shown by flow cytometry. 25810266 4 5 theme life 689:692 arg1 week 681:684 the first week 671:684 the first week of life 671:692 The patient suffered from respiratory distress and episodes of cyanosis with onset in the first week of life and had a nephrotic syndrome. 25810266 5 6 theme epithelial 831:840 arg1 cells 842:846 skin epithelial cells 826:846 skin epithelial cells 826:846 Although there was no clinical evidence for cutaneous fragility, the analysis of a skin sample and of skin epithelial cells enabled the direct assessment of the authentic mutant protein. 25810266 1 7 theme α3 294:295 arg1 subunit 297:303 the integrin α3 subunit 281:303 the integrin α3 subunit (ITGA3) 281:311 Interstitial lung disease, nephrotic syndrome and junctional epidermolysis bullosa is an autosomal recessive multiorgan disorder caused by mutations in the gene for the integrin α3 subunit (ITGA3). 25810266 1 7 theme α3 294:295 arg1 ITGA3 306:310 ITGA3 306:310 ITGA3 306:310 Interstitial lung disease, nephrotic syndrome and junctional epidermolysis bullosa is an autosomal recessive multiorgan disorder caused by mutations in the gene for the integrin α3 subunit (ITGA3). 25810266 9 8 dep onset 1684:1688 arg1 respiratory 1690:1700 respiratory 1690:1700 respiratory 1690:1700 The present report also underscores that ITGA3 mutations may account for atypical cases solely with early onset respiratory and renal involvement. 25810266 1 9 theme lung 129:132 arg1 disease 134:140 Interstitial lung disease 116:140 Interstitial lung disease 116:140 Interstitial lung disease, nephrotic syndrome and junctional epidermolysis bullosa is an autosomal recessive multiorgan disorder caused by mutations in the gene for the integrin α3 subunit (ITGA3). 25810266 1 9 theme lung 129:132 arg1 syndrome 153:160 nephrotic syndrome 143:160 nephrotic syndrome 143:160 Interstitial lung disease, nephrotic syndrome and junctional epidermolysis bullosa is an autosomal recessive multiorgan disorder caused by mutations in the gene for the integrin α3 subunit (ITGA3). 25810266 1 9 theme lung 129:132 arg1 bullosa 191:197 junctional epidermolysis bullosa 166:197 junctional epidermolysis bullosa 166:197 Interstitial lung disease, nephrotic syndrome and junctional epidermolysis bullosa is an autosomal recessive multiorgan disorder caused by mutations in the gene for the integrin α3 subunit (ITGA3). 25810266 1 9 theme lung 129:132 arg1 disorder 236:243 an autosomal recessive multiorgan disorder 202:243 an autosomal recessive multiorgan disorder caused by mutations in the gene for the integrin α3 subunit (ITGA3) 202:311 Interstitial lung disease, nephrotic syndrome and junctional epidermolysis bullosa is an autosomal recessive multiorgan disorder caused by mutations in the gene for the integrin α3 subunit (ITGA3). 25810266 6 10 theme subunit 1021:1027 arg1 subunit 1021:1027 the integrin α3 subunit 1005:1027 the integrin α3 subunit 1005:1027 We show that the mutation altered the conformation of the extracellular β-propeller domain of the integrin α3 subunit preventing correct processing of N-linked oligosaccharides, heterodimerization with β1 integrin and maturation through cleavage into heavy and light chains in the Golgi. 25810266 6 10 theme subunit 1021:1027 arg1 domain 995:1000 the extracellular β-propeller domain 965:1000 the extracellular β-propeller domain of the integrin α3 subunit preventing correct processing of N-linked oligosaccharides, heterodimerization with β1 integrin and maturation through cleavage 965:1155 We show that the mutation altered the conformation of the extracellular β-propeller domain of the integrin α3 subunit preventing correct processing of N-linked oligosaccharides, heterodimerization with β1 integrin and maturation through cleavage into heavy and light chains in the Golgi. 25810266 5 11 theme cutaneous 768:776 arg1 fragility 778:786 cutaneous fragility 768:786 cutaneous fragility 768:786 Although there was no clinical evidence for cutaneous fragility, the analysis of a skin sample and of skin epithelial cells enabled the direct assessment of the authentic mutant protein. 25810266 5 12 theme authentic 885:893 arg1 protein 902:908 the authentic mutant protein 881:908 the authentic mutant protein 881:908 Although there was no clinical evidence for cutaneous fragility, the analysis of a skin sample and of skin epithelial cells enabled the direct assessment of the authentic mutant protein. 25810266 6 13 theme integrin 1009:1016 arg1 subunit 1021:1027 the integrin α3 subunit 1005:1027 the integrin α3 subunit 1005:1027 We show that the mutation altered the conformation of the extracellular β-propeller domain of the integrin α3 subunit preventing correct processing of N-linked oligosaccharides, heterodimerization with β1 integrin and maturation through cleavage into heavy and light chains in the Golgi. 25810266 4 14 theme nephrotic 704:712 arg1 syndrome 714:721 a nephrotic syndrome 702:721 a nephrotic syndrome 702:721 The patient suffered from respiratory distress and episodes of cyanosis with onset in the first week of life and had a nephrotic syndrome. 25810266 0 15 theme lung 79:82 arg1 disease 84:90 interstitial lung disease 66:90 interstitial lung disease 66:90 Crucial role of posttranslational modifications of integrin α3 in interstitial lung disease and nephrotic syndrome. 25810266 1 16 theme junctional 166:175 arg1 disease 134:140 Interstitial lung disease 116:140 Interstitial lung disease 116:140 Interstitial lung disease, nephrotic syndrome and junctional epidermolysis bullosa is an autosomal recessive multiorgan disorder caused by mutations in the gene for the integrin α3 subunit (ITGA3). 25810266 1 16 theme junctional 166:175 arg1 syndrome 153:160 nephrotic syndrome 143:160 nephrotic syndrome 143:160 Interstitial lung disease, nephrotic syndrome and junctional epidermolysis bullosa is an autosomal recessive multiorgan disorder caused by mutations in the gene for the integrin α3 subunit (ITGA3). 25810266 1 16 theme junctional 166:175 arg1 bullosa 191:197 junctional epidermolysis bullosa 166:197 junctional epidermolysis bullosa 166:197 Interstitial lung disease, nephrotic syndrome and junctional epidermolysis bullosa is an autosomal recessive multiorgan disorder caused by mutations in the gene for the integrin α3 subunit (ITGA3). 25810266 1 16 theme junctional 166:175 arg1 disorder 236:243 an autosomal recessive multiorgan disorder 202:243 an autosomal recessive multiorgan disorder caused by mutations in the gene for the integrin α3 subunit (ITGA3) 202:311 Interstitial lung disease, nephrotic syndrome and junctional epidermolysis bullosa is an autosomal recessive multiorgan disorder caused by mutations in the gene for the integrin α3 subunit (ITGA3). 25810266 6 17 theme β-propeller 983:993 arg1 subunit 1021:1027 the integrin α3 subunit 1005:1027 the integrin α3 subunit 1005:1027 We show that the mutation altered the conformation of the extracellular β-propeller domain of the integrin α3 subunit preventing correct processing of N-linked oligosaccharides, heterodimerization with β1 integrin and maturation through cleavage into heavy and light chains in the Golgi. 25810266 6 17 theme β-propeller 983:993 arg1 domain 995:1000 the extracellular β-propeller domain 965:1000 the extracellular β-propeller domain of the integrin α3 subunit preventing correct processing of N-linked oligosaccharides, heterodimerization with β1 integrin and maturation through cleavage 965:1155 We show that the mutation altered the conformation of the extracellular β-propeller domain of the integrin α3 subunit preventing correct processing of N-linked oligosaccharides, heterodimerization with β1 integrin and maturation through cleavage into heavy and light chains in the Golgi. 25810266 7 18 located present 1300:1306 arg1 adhesions 1317:1325 focal adhesions 1311:1325 focal adhesions 1311:1325 Confocal microscopy demonstrated that the mutant protein accumulated intracellularly, but it was not present in focal adhesions or on the cell membrane as shown by flow cytometry. 25810266 7 18 located present 1300:1306 arg2 it 1289:1290 it 1289:1290 it 1289:1290 Confocal microscopy demonstrated that the mutant protein accumulated intracellularly, but it was not present in focal adhesions or on the cell membrane as shown by flow cytometry. 25810266 9 19 theme present 1582:1588 arg1 report 1590:1595 The present report 1578:1595 The present report 1578:1595 The present report also underscores that ITGA3 mutations may account for atypical cases solely with early onset respiratory and renal involvement. 25810266 0 20 theme Crucial 0:6 arg1 role 8:11 Crucial role 0:11 Crucial role of posttranslational modifications of integrin 0:58 Crucial role of posttranslational modifications of integrin α3 in interstitial lung disease and nephrotic syndrome. 25810266 1 21 theme integrin 285:292 arg1 subunit 297:303 the integrin α3 subunit 281:303 the integrin α3 subunit (ITGA3) 281:311 Interstitial lung disease, nephrotic syndrome and junctional epidermolysis bullosa is an autosomal recessive multiorgan disorder caused by mutations in the gene for the integrin α3 subunit (ITGA3). 25810266 1 21 theme integrin 285:292 arg1 ITGA3 306:310 ITGA3 306:310 ITGA3 306:310 Interstitial lung disease, nephrotic syndrome and junctional epidermolysis bullosa is an autosomal recessive multiorgan disorder caused by mutations in the gene for the integrin α3 subunit (ITGA3). 25810266 6 22 theme oligosaccharides 1071:1086 arg1 maturation 1129:1138 maturation 1129:1138 maturation 1129:1138 We show that the mutation altered the conformation of the extracellular β-propeller domain of the integrin α3 subunit preventing correct processing of N-linked oligosaccharides, heterodimerization with β1 integrin and maturation through cleavage into heavy and light chains in the Golgi. 25810266 6 22 theme oligosaccharides 1071:1086 arg1 heterodimerization 1089:1106 heterodimerization 1089:1106 heterodimerization with β1 integrin 1089:1123 We show that the mutation altered the conformation of the extracellular β-propeller domain of the integrin α3 subunit preventing correct processing of N-linked oligosaccharides, heterodimerization with β1 integrin and maturation through cleavage into heavy and light chains in the Golgi. 25810266 6 22 theme oligosaccharides 1071:1086 arg1 processing 1048:1057 correct processing 1040:1057 correct processing of N-linked oligosaccharides 1040:1086 We show that the mutation altered the conformation of the extracellular β-propeller domain of the integrin α3 subunit preventing correct processing of N-linked oligosaccharides, heterodimerization with β1 integrin and maturation through cleavage into heavy and light chains in the Golgi. 25810266 8 23 dep structure 1486:1494 arg1 the 1482:1484 the 1482:1484 the 1482:1484 These findings highlight that single amino acid changes in the integrin α3 subunit may crucially alter the structure and complex processing of this integrin, completely preventing its functionality. 25810266 7 24 theme Confocal 1199:1206 arg1 microscopy 1208:1217 Confocal microscopy 1199:1217 Confocal microscopy 1199:1217 Confocal microscopy demonstrated that the mutant protein accumulated intracellularly, but it was not present in focal adhesions or on the cell membrane as shown by flow cytometry. 25810266 8 25 theme amino 1416:1420 arg1 changes 1427:1433 single amino acid changes 1409:1433 single amino acid changes in the integrin α3 subunit 1409:1460 These findings highlight that single amino acid changes in the integrin α3 subunit may crucially alter the structure and complex processing of this integrin, completely preventing its functionality. 25810266 0 26 theme modifications 34:46 arg1 role 8:11 Crucial role 0:11 Crucial role of posttranslational modifications of integrin 0:58 Crucial role of posttranslational modifications of integrin α3 in interstitial lung disease and nephrotic syndrome. 25810266 7 27 from adhesions 1317:1325 arg1 present 1300:1306 present 1300:1306 present 1300:1306 Confocal microscopy demonstrated that the mutant protein accumulated intracellularly, but it was not present in focal adhesions or on the cell membrane as shown by flow cytometry. 25810266 6 28 theme correct 1040:1046 arg1 processing 1048:1057 correct processing 1040:1057 correct processing of N-linked oligosaccharides 1040:1086 We show that the mutation altered the conformation of the extracellular β-propeller domain of the integrin α3 subunit preventing correct processing of N-linked oligosaccharides, heterodimerization with β1 integrin and maturation through cleavage into heavy and light chains in the Golgi. 25810266 7 29 attach present 1300:1306 arg1 membrane 1342:1349 the cell membrane 1333:1349 the cell membrane 1333:1349 Confocal microscopy demonstrated that the mutant protein accumulated intracellularly, but it was not present in focal adhesions or on the cell membrane as shown by flow cytometry. 25810266 7 29 attach present 1300:1306 arg1 adhesions 1317:1325 focal adhesions 1311:1325 focal adhesions 1311:1325 Confocal microscopy demonstrated that the mutant protein accumulated intracellularly, but it was not present in focal adhesions or on the cell membrane as shown by flow cytometry. 25810266 7 29 attach present 1300:1306 arg2 it 1289:1290 it 1289:1290 it 1289:1290 Confocal microscopy demonstrated that the mutant protein accumulated intracellularly, but it was not present in focal adhesions or on the cell membrane as shown by flow cytometry. 25810266 2 30 theme manifestations 335:348 arg1 spectrum 323:330 The full spectrum 314:330 The full spectrum of manifestations and genotype-phenotype correlations 314:384 The full spectrum of manifestations and genotype-phenotype correlations is still poorly characterized. 25810266 0 31 theme integrin 51:58 arg1 modifications 34:46 posttranslational modifications 16:46 posttranslational modifications of integrin 16:58 Crucial role of posttranslational modifications of integrin α3 in interstitial lung disease and nephrotic syndrome. 25810266 6 32 with processing 1048:1057 arg1 integrin 1116:1123 β1 integrin 1113:1123 β1 integrin 1113:1123 We show that the mutation altered the conformation of the extracellular β-propeller domain of the integrin α3 subunit preventing correct processing of N-linked oligosaccharides, heterodimerization with β1 integrin and maturation through cleavage into heavy and light chains in the Golgi. 25810266 7 33 theme focal 1311:1315 arg1 adhesions 1317:1325 focal adhesions 1311:1325 focal adhesions 1311:1325 Confocal microscopy demonstrated that the mutant protein accumulated intracellularly, but it was not present in focal adhesions or on the cell membrane as shown by flow cytometry. 25810266 9 34 theme atypical 1651:1658 arg1 cases 1660:1664 atypical cases 1651:1664 atypical cases solely with early onset respiratory and renal involvement 1651:1722 The present report also underscores that ITGA3 mutations may account for atypical cases solely with early onset respiratory and renal involvement. 25810266 9 35 with cases 1660:1664 arg1 onset 1684:1688 early onset respiratory and renal involvement 1678:1722 onset 1684:1688 The present report also underscores that ITGA3 mutations may account for atypical cases solely with early onset respiratory and renal involvement. 25810266 9 35 with cases 1660:1664 arg1 involvement 1712:1722 renal involvement 1706:1722 renal involvement 1706:1722 The present report also underscores that ITGA3 mutations may account for atypical cases solely with early onset respiratory and renal involvement. 25810266 8 36 theme α3 1451:1452 arg1 subunit 1454:1460 the integrin α3 subunit 1438:1460 the integrin α3 subunit 1438:1460 These findings highlight that single amino acid changes in the integrin α3 subunit may crucially alter the structure and complex processing of this integrin, completely preventing its functionality. 25810266 2 37 theme genotype-phenotype 354:371 arg1 correlations 373:384 genotype-phenotype correlations 354:384 genotype-phenotype correlations 354:384 The full spectrum of manifestations and genotype-phenotype correlations is still poorly characterized. 25810266 9 38 theme early 1678:1682 arg1 onset 1684:1688 early onset respiratory and renal involvement 1678:1722 onset 1684:1688 The present report also underscores that ITGA3 mutations may account for atypical cases solely with early onset respiratory and renal involvement. 25810266 6 39 theme β1 1113:1114 arg1 integrin 1116:1123 β1 integrin 1113:1123 β1 integrin 1113:1123 We show that the mutation altered the conformation of the extracellular β-propeller domain of the integrin α3 subunit preventing correct processing of N-linked oligosaccharides, heterodimerization with β1 integrin and maturation through cleavage into heavy and light chains in the Golgi. 25810266 4 40 contain had 698:700 arg2 syndrome 714:721 a nephrotic syndrome 702:721 a nephrotic syndrome 702:721 The patient suffered from respiratory distress and episodes of cyanosis with onset in the first week of life and had a nephrotic syndrome. 25810266 4 40 contain had 698:700 arg1 patient 589:595 The patient 585:595 The patient 585:595 The patient suffered from respiratory distress and episodes of cyanosis with onset in the first week of life and had a nephrotic syndrome. 25810266 4 41 theme respiratory 611:621 arg1 distress 623:630 respiratory distress 611:630 respiratory distress 611:630 The patient suffered from respiratory distress and episodes of cyanosis with onset in the first week of life and had a nephrotic syndrome. 25810266 3 42 theme ITGA3 514:518 arg1 mutation 520:527 a homozygous ITGA3 mutation 501:527 a homozygous ITGA3 mutation leading to the single amino acid substitution, p.R463W 501:582 Here, we uncovered the disease-causing role and the molecular mechanisms underlying a homozygous ITGA3 mutation leading to the single amino acid substitution, p.R463W. 25810266 3 43 theme amino 551:555 arg1 substitution 562:573 the single amino acid substitution 540:573 the single amino acid substitution 540:573 Here, we uncovered the disease-causing role and the molecular mechanisms underlying a homozygous ITGA3 mutation leading to the single amino acid substitution, p.R463W. 25810266 3 43 theme amino 551:555 arg1 p.R463W 576:582 p.R463W 576:582 p.R463W 576:582 Here, we uncovered the disease-causing role and the molecular mechanisms underlying a homozygous ITGA3 mutation leading to the single amino acid substitution, p.R463W. 25810266 1 44 theme epidermolysis 177:189 arg1 disease 134:140 Interstitial lung disease 116:140 Interstitial lung disease 116:140 Interstitial lung disease, nephrotic syndrome and junctional epidermolysis bullosa is an autosomal recessive multiorgan disorder caused by mutations in the gene for the integrin α3 subunit (ITGA3). 25810266 1 44 theme epidermolysis 177:189 arg1 syndrome 153:160 nephrotic syndrome 143:160 nephrotic syndrome 143:160 Interstitial lung disease, nephrotic syndrome and junctional epidermolysis bullosa is an autosomal recessive multiorgan disorder caused by mutations in the gene for the integrin α3 subunit (ITGA3). 25810266 1 44 theme epidermolysis 177:189 arg1 bullosa 191:197 junctional epidermolysis bullosa 166:197 junctional epidermolysis bullosa 166:197 Interstitial lung disease, nephrotic syndrome and junctional epidermolysis bullosa is an autosomal recessive multiorgan disorder caused by mutations in the gene for the integrin α3 subunit (ITGA3). 25810266 1 44 theme epidermolysis 177:189 arg1 disorder 236:243 an autosomal recessive multiorgan disorder 202:243 an autosomal recessive multiorgan disorder caused by mutations in the gene for the integrin α3 subunit (ITGA3) 202:311 Interstitial lung disease, nephrotic syndrome and junctional epidermolysis bullosa is an autosomal recessive multiorgan disorder caused by mutations in the gene for the integrin α3 subunit (ITGA3). 25810266 6 45 with maturation 1129:1138 arg1 integrin 1116:1123 β1 integrin 1113:1123 β1 integrin 1113:1123 We show that the mutation altered the conformation of the extracellular β-propeller domain of the integrin α3 subunit preventing correct processing of N-linked oligosaccharides, heterodimerization with β1 integrin and maturation through cleavage into heavy and light chains in the Golgi. 25810266 9 46 theme renal 1706:1710 arg1 involvement 1712:1722 renal involvement 1706:1722 renal involvement 1706:1722 The present report also underscores that ITGA3 mutations may account for atypical cases solely with early onset respiratory and renal involvement. 25810266 4 47 theme first 675:679 arg1 week 681:684 the first week 671:684 the first week of life 671:692 The patient suffered from respiratory distress and episodes of cyanosis with onset in the first week of life and had a nephrotic syndrome. 25810266 6 48 theme extracellular 969:981 arg1 subunit 1021:1027 the integrin α3 subunit 1005:1027 the integrin α3 subunit 1005:1027 We show that the mutation altered the conformation of the extracellular β-propeller domain of the integrin α3 subunit preventing correct processing of N-linked oligosaccharides, heterodimerization with β1 integrin and maturation through cleavage into heavy and light chains in the Golgi. 25810266 6 48 theme extracellular 969:981 arg1 domain 995:1000 the extracellular β-propeller domain 965:1000 the extracellular β-propeller domain of the integrin α3 subunit preventing correct processing of N-linked oligosaccharides, heterodimerization with β1 integrin and maturation through cleavage 965:1155 We show that the mutation altered the conformation of the extracellular β-propeller domain of the integrin α3 subunit preventing correct processing of N-linked oligosaccharides, heterodimerization with β1 integrin and maturation through cleavage into heavy and light chains in the Golgi. 25810266 1 49 theme autosomal 205:213 arg1 disease 134:140 Interstitial lung disease 116:140 Interstitial lung disease 116:140 Interstitial lung disease, nephrotic syndrome and junctional epidermolysis bullosa is an autosomal recessive multiorgan disorder caused by mutations in the gene for the integrin α3 subunit (ITGA3). 25810266 1 49 theme autosomal 205:213 arg1 syndrome 153:160 nephrotic syndrome 143:160 nephrotic syndrome 143:160 Interstitial lung disease, nephrotic syndrome and junctional epidermolysis bullosa is an autosomal recessive multiorgan disorder caused by mutations in the gene for the integrin α3 subunit (ITGA3). 25810266 1 49 theme autosomal 205:213 arg1 bullosa 191:197 junctional epidermolysis bullosa 166:197 junctional epidermolysis bullosa 166:197 Interstitial lung disease, nephrotic syndrome and junctional epidermolysis bullosa is an autosomal recessive multiorgan disorder caused by mutations in the gene for the integrin α3 subunit (ITGA3). 25810266 1 49 theme autosomal 205:213 arg1 disorder 236:243 an autosomal recessive multiorgan disorder 202:243 an autosomal recessive multiorgan disorder caused by mutations in the gene for the integrin α3 subunit (ITGA3) 202:311 Interstitial lung disease, nephrotic syndrome and junctional epidermolysis bullosa is an autosomal recessive multiorgan disorder caused by mutations in the gene for the integrin α3 subunit (ITGA3). 25810266 5 50 theme protein 902:908 arg1 assessment 867:876 the direct assessment 856:876 the direct assessment of the authentic mutant protein 856:908 Although there was no clinical evidence for cutaneous fragility, the analysis of a skin sample and of skin epithelial cells enabled the direct assessment of the authentic mutant protein. 25810266 5 51 theme cells 842:846 arg1 analysis 793:800 the analysis 789:800 the analysis of a skin sample and of skin epithelial cells 789:846 Although there was no clinical evidence for cutaneous fragility, the analysis of a skin sample and of skin epithelial cells enabled the direct assessment of the authentic mutant protein. 25810266 1 52 from mutations 255:263 arg1 gene 272:275 the gene 268:275 the gene for the integrin α3 subunit (ITGA3) 268:311 Interstitial lung disease, nephrotic syndrome and junctional epidermolysis bullosa is an autosomal recessive multiorgan disorder caused by mutations in the gene for the integrin α3 subunit (ITGA3). 25810266 4 53 with episodes 636:643 arg1 onset 662:666 onset 662:666 onset 662:666 The patient suffered from respiratory distress and episodes of cyanosis with onset in the first week of life and had a nephrotic syndrome. 25810266 1 54 theme Interstitial 116:127 arg1 disease 134:140 Interstitial lung disease 116:140 Interstitial lung disease 116:140 Interstitial lung disease, nephrotic syndrome and junctional epidermolysis bullosa is an autosomal recessive multiorgan disorder caused by mutations in the gene for the integrin α3 subunit (ITGA3). 25810266 1 54 theme Interstitial 116:127 arg1 syndrome 153:160 nephrotic syndrome 143:160 nephrotic syndrome 143:160 Interstitial lung disease, nephrotic syndrome and junctional epidermolysis bullosa is an autosomal recessive multiorgan disorder caused by mutations in the gene for the integrin α3 subunit (ITGA3). 25810266 1 54 theme Interstitial 116:127 arg1 bullosa 191:197 junctional epidermolysis bullosa 166:197 junctional epidermolysis bullosa 166:197 Interstitial lung disease, nephrotic syndrome and junctional epidermolysis bullosa is an autosomal recessive multiorgan disorder caused by mutations in the gene for the integrin α3 subunit (ITGA3). 25810266 1 54 theme Interstitial 116:127 arg1 disorder 236:243 an autosomal recessive multiorgan disorder 202:243 an autosomal recessive multiorgan disorder caused by mutations in the gene for the integrin α3 subunit (ITGA3) 202:311 Interstitial lung disease, nephrotic syndrome and junctional epidermolysis bullosa is an autosomal recessive multiorgan disorder caused by mutations in the gene for the integrin α3 subunit (ITGA3). 25810266 4 55 with distress 623:630 arg1 onset 662:666 onset 662:666 onset 662:666 The patient suffered from respiratory distress and episodes of cyanosis with onset in the first week of life and had a nephrotic syndrome. 25810266 8 56 theme complex 1500:1506 arg1 processing 1508:1517 complex processing 1500:1517 complex processing 1500:1517 These findings highlight that single amino acid changes in the integrin α3 subunit may crucially alter the structure and complex processing of this integrin, completely preventing its functionality. 25810266 0 57 theme interstitial 66:77 arg1 disease 84:90 interstitial lung disease 66:90 interstitial lung disease 66:90 Crucial role of posttranslational modifications of integrin α3 in interstitial lung disease and nephrotic syndrome. 25810266 5 58 theme skin 826:829 arg1 cells 842:846 skin epithelial cells 826:846 skin epithelial cells 826:846 Although there was no clinical evidence for cutaneous fragility, the analysis of a skin sample and of skin epithelial cells enabled the direct assessment of the authentic mutant protein. 25810266 1 59 theme nephrotic 143:151 arg1 disease 134:140 Interstitial lung disease 116:140 Interstitial lung disease 116:140 Interstitial lung disease, nephrotic syndrome and junctional epidermolysis bullosa is an autosomal recessive multiorgan disorder caused by mutations in the gene for the integrin α3 subunit (ITGA3). 25810266 1 59 theme nephrotic 143:151 arg1 syndrome 153:160 nephrotic syndrome 143:160 nephrotic syndrome 143:160 Interstitial lung disease, nephrotic syndrome and junctional epidermolysis bullosa is an autosomal recessive multiorgan disorder caused by mutations in the gene for the integrin α3 subunit (ITGA3). 25810266 1 59 theme nephrotic 143:151 arg1 bullosa 191:197 junctional epidermolysis bullosa 166:197 junctional epidermolysis bullosa 166:197 Interstitial lung disease, nephrotic syndrome and junctional epidermolysis bullosa is an autosomal recessive multiorgan disorder caused by mutations in the gene for the integrin α3 subunit (ITGA3). 25810266 1 59 theme nephrotic 143:151 arg1 disorder 236:243 an autosomal recessive multiorgan disorder 202:243 an autosomal recessive multiorgan disorder caused by mutations in the gene for the integrin α3 subunit (ITGA3) 202:311 Interstitial lung disease, nephrotic syndrome and junctional epidermolysis bullosa is an autosomal recessive multiorgan disorder caused by mutations in the gene for the integrin α3 subunit (ITGA3). 25810266 6 60 theme α3 1018:1019 arg1 subunit 1021:1027 the integrin α3 subunit 1005:1027 the integrin α3 subunit 1005:1027 We show that the mutation altered the conformation of the extracellular β-propeller domain of the integrin α3 subunit preventing correct processing of N-linked oligosaccharides, heterodimerization with β1 integrin and maturation through cleavage into heavy and light chains in the Golgi. 25810266 7 61 theme flow 1363:1366 arg1 cytometry 1368:1376 flow cytometry 1363:1376 flow cytometry 1363:1376 Confocal microscopy demonstrated that the mutant protein accumulated intracellularly, but it was not present in focal adhesions or on the cell membrane as shown by flow cytometry. 25810266 7 62 theme mutant 1241:1246 arg1 protein 1248:1254 the mutant protein 1237:1254 the mutant protein 1237:1254 Confocal microscopy demonstrated that the mutant protein accumulated intracellularly, but it was not present in focal adhesions or on the cell membrane as shown by flow cytometry. 25810266 5 63 theme mutant 895:900 arg1 protein 902:908 the authentic mutant protein 881:908 the authentic mutant protein 881:908 Although there was no clinical evidence for cutaneous fragility, the analysis of a skin sample and of skin epithelial cells enabled the direct assessment of the authentic mutant protein. 25810266 8 64 theme integrin 1527:1534 arg1 structure 1486:1494 structure 1486:1494 structure 1486:1494 These findings highlight that single amino acid changes in the integrin α3 subunit may crucially alter the structure and complex processing of this integrin, completely preventing its functionality. 25810266 8 64 theme integrin 1527:1534 arg1 processing 1508:1517 complex processing 1500:1517 complex processing 1500:1517 These findings highlight that single amino acid changes in the integrin α3 subunit may crucially alter the structure and complex processing of this integrin, completely preventing its functionality. 25810266 0 65 theme nephrotic 96:104 arg1 syndrome 106:113 nephrotic syndrome 96:113 nephrotic syndrome 96:113 Crucial role of posttranslational modifications of integrin α3 in interstitial lung disease and nephrotic syndrome. 25810266 6 66 theme domain 995:1000 arg1 conformation 949:960 the conformation 945:960 the conformation of the extracellular β-propeller domain of the integrin α3 subunit preventing correct processing of N-linked oligosaccharides, heterodimerization with β1 integrin and maturation through cleavage 945:1155 We show that the mutation altered the conformation of the extracellular β-propeller domain of the integrin α3 subunit preventing correct processing of N-linked oligosaccharides, heterodimerization with β1 integrin and maturation through cleavage into heavy and light chains in the Golgi. 25810266 6 67 dep heavy 1162:1166 arg1 chains 1178:1183 chains 1178:1183 chains 1178:1183 We show that the mutation altered the conformation of the extracellular β-propeller domain of the integrin α3 subunit preventing correct processing of N-linked oligosaccharides, heterodimerization with β1 integrin and maturation through cleavage into heavy and light chains in the Golgi. 25810266 6 68 from Golgi 1192:1196 arg1 heavy 1162:1166 heavy 1162:1166 heavy 1162:1166 We show that the mutation altered the conformation of the extracellular β-propeller domain of the integrin α3 subunit preventing correct processing of N-linked oligosaccharides, heterodimerization with β1 integrin and maturation through cleavage into heavy and light chains in the Golgi. 25810266 2 69 theme full 318:321 arg1 spectrum 323:330 The full spectrum 314:330 The full spectrum of manifestations and genotype-phenotype correlations 314:384 The full spectrum of manifestations and genotype-phenotype correlations is still poorly characterized. 25810266 5 70 theme clinical 746:753 arg1 evidence 755:762 no clinical evidence 743:762 no clinical evidence for cutaneous fragility 743:786 Although there was no clinical evidence for cutaneous fragility, the analysis of a skin sample and of skin epithelial cells enabled the direct assessment of the authentic mutant protein. 25810266 1 71 theme recessive 215:223 arg1 disease 134:140 Interstitial lung disease 116:140 Interstitial lung disease 116:140 Interstitial lung disease, nephrotic syndrome and junctional epidermolysis bullosa is an autosomal recessive multiorgan disorder caused by mutations in the gene for the integrin α3 subunit (ITGA3). 25810266 1 71 theme recessive 215:223 arg1 syndrome 153:160 nephrotic syndrome 143:160 nephrotic syndrome 143:160 Interstitial lung disease, nephrotic syndrome and junctional epidermolysis bullosa is an autosomal recessive multiorgan disorder caused by mutations in the gene for the integrin α3 subunit (ITGA3). 25810266 1 71 theme recessive 215:223 arg1 bullosa 191:197 junctional epidermolysis bullosa 166:197 junctional epidermolysis bullosa 166:197 Interstitial lung disease, nephrotic syndrome and junctional epidermolysis bullosa is an autosomal recessive multiorgan disorder caused by mutations in the gene for the integrin α3 subunit (ITGA3). 25810266 1 71 theme recessive 215:223 arg1 disorder 236:243 an autosomal recessive multiorgan disorder 202:243 an autosomal recessive multiorgan disorder caused by mutations in the gene for the integrin α3 subunit (ITGA3) 202:311 Interstitial lung disease, nephrotic syndrome and junctional epidermolysis bullosa is an autosomal recessive multiorgan disorder caused by mutations in the gene for the integrin α3 subunit (ITGA3). 25810266 5 72 theme skin 807:810 arg1 sample 812:817 a skin sample 805:817 a skin sample 805:817 Although there was no clinical evidence for cutaneous fragility, the analysis of a skin sample and of skin epithelial cells enabled the direct assessment of the authentic mutant protein. 25810266 7 73 theme cell 1337:1340 arg1 membrane 1342:1349 the cell membrane 1333:1349 the cell membrane 1333:1349 Confocal microscopy demonstrated that the mutant protein accumulated intracellularly, but it was not present in focal adhesions or on the cell membrane as shown by flow cytometry. 25810266 3 74 theme disease-causing 440:454 arg1 role 456:459 the disease-causing role 436:459 the disease-causing role 436:459 Here, we uncovered the disease-causing role and the molecular mechanisms underlying a homozygous ITGA3 mutation leading to the single amino acid substitution, p.R463W. 25810266 0 75 theme posttranslational 16:32 arg1 modifications 34:46 posttranslational modifications 16:46 posttranslational modifications of integrin 16:58 Crucial role of posttranslational modifications of integrin α3 in interstitial lung disease and nephrotic syndrome. 25810266 5 76 theme sample 812:817 arg1 analysis 793:800 the analysis 789:800 the analysis of a skin sample and of skin epithelial cells 789:846 Although there was no clinical evidence for cutaneous fragility, the analysis of a skin sample and of skin epithelial cells enabled the direct assessment of the authentic mutant protein. 25810266 6 77 theme N-linked 1062:1069 arg1 oligosaccharides 1071:1086 N-linked oligosaccharides 1062:1086 N-linked oligosaccharides 1062:1086 We show that the mutation altered the conformation of the extracellular β-propeller domain of the integrin α3 subunit preventing correct processing of N-linked oligosaccharides, heterodimerization with β1 integrin and maturation through cleavage into heavy and light chains in the Golgi. 25810266 1 78 theme multiorgan 225:234 arg1 disease 134:140 Interstitial lung disease 116:140 Interstitial lung disease 116:140 Interstitial lung disease, nephrotic syndrome and junctional epidermolysis bullosa is an autosomal recessive multiorgan disorder caused by mutations in the gene for the integrin α3 subunit (ITGA3). 25810266 1 78 theme multiorgan 225:234 arg1 syndrome 153:160 nephrotic syndrome 143:160 nephrotic syndrome 143:160 Interstitial lung disease, nephrotic syndrome and junctional epidermolysis bullosa is an autosomal recessive multiorgan disorder caused by mutations in the gene for the integrin α3 subunit (ITGA3). 25810266 1 78 theme multiorgan 225:234 arg1 bullosa 191:197 junctional epidermolysis bullosa 166:197 junctional epidermolysis bullosa 166:197 Interstitial lung disease, nephrotic syndrome and junctional epidermolysis bullosa is an autosomal recessive multiorgan disorder caused by mutations in the gene for the integrin α3 subunit (ITGA3). 25810266 1 78 theme multiorgan 225:234 arg1 disorder 236:243 an autosomal recessive multiorgan disorder 202:243 an autosomal recessive multiorgan disorder caused by mutations in the gene for the integrin α3 subunit (ITGA3) 202:311 Interstitial lung disease, nephrotic syndrome and junctional epidermolysis bullosa is an autosomal recessive multiorgan disorder caused by mutations in the gene for the integrin α3 subunit (ITGA3). 25810266 9 79 theme ITGA3 1619:1623 arg1 mutations 1625:1633 ITGA3 mutations 1619:1633 ITGA3 mutations 1619:1633 The present report also underscores that ITGA3 mutations may account for atypical cases solely with early onset respiratory and renal involvement. 25810266 8 80 theme single 1409:1414 arg1 changes 1427:1433 single amino acid changes 1409:1433 single amino acid changes in the integrin α3 subunit 1409:1460 These findings highlight that single amino acid changes in the integrin α3 subunit may crucially alter the structure and complex processing of this integrin, completely preventing its functionality. 25810266 3 81 theme molecular 469:477 arg1 mechanisms 479:488 the molecular mechanisms 465:488 the molecular mechanisms underlying a homozygous ITGA3 mutation leading to the single amino acid substitution, p.R463W 465:582 Here, we uncovered the disease-causing role and the molecular mechanisms underlying a homozygous ITGA3 mutation leading to the single amino acid substitution, p.R463W. 25810266 6 82 with heterodimerization 1089:1106 arg1 integrin 1116:1123 β1 integrin 1113:1123 β1 integrin 1113:1123 We show that the mutation altered the conformation of the extracellular β-propeller domain of the integrin α3 subunit preventing correct processing of N-linked oligosaccharides, heterodimerization with β1 integrin and maturation through cleavage into heavy and light chains in the Golgi. 25810266 2 83 theme correlations 373:384 arg1 spectrum 323:330 The full spectrum 314:330 The full spectrum of manifestations and genotype-phenotype correlations 314:384 The full spectrum of manifestations and genotype-phenotype correlations is still poorly characterized. 25810266 8 84 theme acid 1422:1425 arg1 changes 1427:1433 single amino acid changes 1409:1433 single amino acid changes in the integrin α3 subunit 1409:1460 These findings highlight that single amino acid changes in the integrin α3 subunit may crucially alter the structure and complex processing of this integrin, completely preventing its functionality. 25810266 6 85 from heavy 1162:1166 arg1 Golgi 1192:1196 the Golgi 1188:1196 the Golgi 1188:1196 We show that the mutation altered the conformation of the extracellular β-propeller domain of the integrin α3 subunit preventing correct processing of N-linked oligosaccharides, heterodimerization with β1 integrin and maturation through cleavage into heavy and light chains in the Golgi. 25810266 3 86 theme homozygous 503:512 arg1 mutation 520:527 a homozygous ITGA3 mutation 501:527 a homozygous ITGA3 mutation leading to the single amino acid substitution, p.R463W 501:582 Here, we uncovered the disease-causing role and the molecular mechanisms underlying a homozygous ITGA3 mutation leading to the single amino acid substitution, p.R463W. 25810266 4 87 theme cyanosis 648:655 arg1 episodes 636:643 episodes 636:643 episodes of cyanosis with onset 636:666 The patient suffered from respiratory distress and episodes of cyanosis with onset in the first week of life and had a nephrotic syndrome. 25810266 4 87 theme cyanosis 648:655 arg1 distress 623:630 respiratory distress 611:630 respiratory distress 611:630 The patient suffered from respiratory distress and episodes of cyanosis with onset in the first week of life and had a nephrotic syndrome. 25810266 8 88 theme integrin 1442:1449 arg1 subunit 1454:1460 the integrin α3 subunit 1438:1460 the integrin α3 subunit 1438:1460 These findings highlight that single amino acid changes in the integrin α3 subunit may crucially alter the structure and complex processing of this integrin, completely preventing its functionality. 25810266 3 89 theme single 544:549 arg1 substitution 562:573 the single amino acid substitution 540:573 the single amino acid substitution 540:573 Here, we uncovered the disease-causing role and the molecular mechanisms underlying a homozygous ITGA3 mutation leading to the single amino acid substitution, p.R463W. 25810266 3 89 theme single 544:549 arg1 p.R463W 576:582 p.R463W 576:582 p.R463W 576:582 Here, we uncovered the disease-causing role and the molecular mechanisms underlying a homozygous ITGA3 mutation leading to the single amino acid substitution, p.R463W. 25710686 4 0 theme osteoblast 737:746 arg1 colonies 748:755 osteoblast colonies 737:755 osteoblast colonies (bone nodules) 737:770 MCC BSP-/- cultures exhibit fewer fibroblast (CFU-F), preosteoblast (CFU-ALP) and osteoblast colonies (bone nodules) than wild type, indicative of a lower number of osteoprogenitors. 25710686 4 0 theme osteoblast 737:746 arg1 nodules 763:769 bone nodules 758:769 bone nodules 758:769 MCC BSP-/- cultures exhibit fewer fibroblast (CFU-F), preosteoblast (CFU-ALP) and osteoblast colonies (bone nodules) than wild type, indicative of a lower number of osteoprogenitors. 25710686 9 1 theme effective 1700:1708 arg1 skeletogenesis 1710:1723 the effective skeletogenesis 1696:1723 the effective skeletogenesis 1696:1723 Altogether, we found that BSP regulates mouse calvaria osteoblast cell clonogenicity, differentiation and activity in vitro in a cell density dependent manner, consistent with the effective skeletogenesis but the low levels of bone formation observed in vivo. 25710686 3 2 theme BSP 587:589 arg1 absence 576:582 the absence 572:582 the absence of BSP 572:589 Because baseline bone formation activity is constitutively lower in BSP-/- mice, we studied the impact of the absence of BSP on in vitro osteogenesis in mouse calvaria cell (MCC) cultures. 25710686 6 3 theme early 1113:1117 arg1 times 1127:1131 early culture times 1113:1131 early culture times 1113:1131 Osteopontin (OPN) is the only SIBLING expressed in standard density BSP-/- culture, at higher levels than in wild type in early culture times. 25710686 6 4 from levels 1085:1090 arg1 SIBLING 1021:1027 the only SIBLING 1012:1027 the only SIBLING expressed in standard density BSP-/- culture 1012:1072 Osteopontin (OPN) is the only SIBLING expressed in standard density BSP-/- culture, at higher levels than in wild type in early culture times. 25710686 6 4 from levels 1085:1090 arg1 type 1105:1108 wild type 1100:1108 wild type in early culture times 1100:1131 Osteopontin (OPN) is the only SIBLING expressed in standard density BSP-/- culture, at higher levels than in wild type in early culture times. 25710686 6 4 from levels 1085:1090 arg1 Osteopontin 991:1001 Osteopontin 991:1001 Osteopontin (OPN) 991:1007 Osteopontin (OPN) is the only SIBLING expressed in standard density BSP-/- culture, at higher levels than in wild type in early culture times. 25710686 7 5 theme osteoblast 1243:1252 arg1 markers 1254:1260 osteoblast markers 1243:1260 osteoblast markers 1243:1260 At higher plating density, the effects of the absence of BSP were partly rescued, with resumed expression of osteoblast markers and cognate SIBLING proteins, and mineralization of the mutant cultures. 25710686 3 6 theme mouse 619:623 arg1 cultures 645:652 mouse calvaria cell (MCC) cultures 619:652 mouse calvaria cell (MCC) cultures 619:652 Because baseline bone formation activity is constitutively lower in BSP-/- mice, we studied the impact of the absence of BSP on in vitro osteogenesis in mouse calvaria cell (MCC) cultures. 25710686 2 7 contain have 376:379 arg2 mass 395:398 a higher bone mass 381:398 a higher bone mass than wild type (BSP+/+) littermates 381:434 BSP is strongly expressed in bone and we previously showed that BSP knockout (BSP-/-) mice have a higher bone mass than wild type (BSP+/+) littermates, with lower bone remodelling. 25710686 2 7 contain have 376:379 arg1 mice 371:374 BSP knockout (BSP-/-) mice 349:374 BSP knockout (BSP-/-) mice 349:374 BSP is strongly expressed in bone and we previously showed that BSP knockout (BSP-/-) mice have a higher bone mass than wild type (BSP+/+) littermates, with lower bone remodelling. 25710686 7 8 theme proteins 1282:1289 arg1 mineralization 1296:1309 mineralization 1296:1309 mineralization of the mutant cultures 1296:1332 At higher plating density, the effects of the absence of BSP were partly rescued, with resumed expression of osteoblast markers and cognate SIBLING proteins, and mineralization of the mutant cultures. 25710686 7 8 theme proteins 1282:1289 arg1 expression 1229:1238 resumed expression 1221:1238 resumed expression of osteoblast markers and cognate SIBLING proteins 1221:1289 At higher plating density, the effects of the absence of BSP were partly rescued, with resumed expression of osteoblast markers and cognate SIBLING proteins, and mineralization of the mutant cultures. 25710686 6 9 theme only 1016:1019 arg1 SIBLING 1021:1027 the only SIBLING 1012:1027 the only SIBLING expressed in standard density BSP-/- culture 1012:1072 Osteopontin (OPN) is the only SIBLING expressed in standard density BSP-/- culture, at higher levels than in wild type in early culture times. 25710686 6 9 theme only 1016:1019 arg1 Osteopontin 991:1001 Osteopontin 991:1001 Osteopontin (OPN) 991:1007 Osteopontin (OPN) is the only SIBLING expressed in standard density BSP-/- culture, at higher levels than in wild type in early culture times. 25710686 9 10 theme low 1733:1735 arg1 levels 1737:1742 the low levels 1729:1742 the low levels of bone formation observed in vivo 1729:1777 Altogether, we found that BSP regulates mouse calvaria osteoblast cell clonogenicity, differentiation and activity in vitro in a cell density dependent manner, consistent with the effective skeletogenesis but the low levels of bone formation observed in vivo. 25710686 3 11 from impact 562:567 arg1 osteogenesis 603:614 in vitro osteogenesis 594:614 in vitro osteogenesis in mouse calvaria cell (MCC) cultures 594:652 Because baseline bone formation activity is constitutively lower in BSP-/- mice, we studied the impact of the absence of BSP on in vitro osteogenesis in mouse calvaria cell (MCC) cultures. 25710686 7 12 theme cognate 1266:1272 arg1 proteins 1282:1289 cognate SIBLING proteins 1266:1289 cognate SIBLING proteins 1266:1289 At higher plating density, the effects of the absence of BSP were partly rescued, with resumed expression of osteoblast markers and cognate SIBLING proteins, and mineralization of the mutant cultures. 25710686 3 13 theme MCC 640:642 arg1 cultures 645:652 mouse calvaria cell (MCC) cultures 619:652 mouse calvaria cell (MCC) cultures 619:652 Because baseline bone formation activity is constitutively lower in BSP-/- mice, we studied the impact of the absence of BSP on in vitro osteogenesis in mouse calvaria cell (MCC) cultures. 25710686 3 14 theme formation 488:496 arg1 activity 498:505 baseline bone formation activity 474:505 baseline bone formation activity 474:505 Because baseline bone formation activity is constitutively lower in BSP-/- mice, we studied the impact of the absence of BSP on in vitro osteogenesis in mouse calvaria cell (MCC) cultures. 25710686 9 15 theme formation 1752:1760 arg1 levels 1737:1742 the low levels 1729:1742 the low levels of bone formation observed in vivo 1729:1777 Altogether, we found that BSP regulates mouse calvaria osteoblast cell clonogenicity, differentiation and activity in vitro in a cell density dependent manner, consistent with the effective skeletogenesis but the low levels of bone formation observed in vivo. 25710686 3 16 theme cell 634:637 arg1 cultures 645:652 mouse calvaria cell (MCC) cultures 619:652 mouse calvaria cell (MCC) cultures 619:652 Because baseline bone formation activity is constitutively lower in BSP-/- mice, we studied the impact of the absence of BSP on in vitro osteogenesis in mouse calvaria cell (MCC) cultures. 25710686 3 17 theme baseline 474:481 arg1 formation 488:496 baseline bone formation 474:496 baseline bone formation activity 474:505 Because baseline bone formation activity is constitutively lower in BSP-/- mice, we studied the impact of the absence of BSP on in vitro osteogenesis in mouse calvaria cell (MCC) cultures. 25710686 1 18 theme integrin-binding 163:178 arg1 family 220:225 the "small integrin-binding ligand N-linked glycoprotein" (SIBLING) family 152:225 the "small integrin-binding ligand N-linked glycoprotein" (SIBLING) family 152:225 Bone sialoprotein (BSP) belongs to the "small integrin-binding ligand N-linked glycoprotein" (SIBLING) family, whose members interact with bone cells and bone mineral. 25710686 4 19 theme indicative 788:797 arg1 type 782:785 wild type 777:785 wild type 777:785 MCC BSP-/- cultures exhibit fewer fibroblast (CFU-F), preosteoblast (CFU-ALP) and osteoblast colonies (bone nodules) than wild type, indicative of a lower number of osteoprogenitors. 25710686 6 20 theme higher 1078:1083 arg1 levels 1085:1090 higher levels 1078:1090 higher levels than in wild type in early culture times 1078:1131 Osteopontin (OPN) is the only SIBLING expressed in standard density BSP-/- culture, at higher levels than in wild type in early culture times. 25710686 5 21 theme osteogenic 938:947 arg1 markers 949:955 osteogenic markers 938:955 osteogenic markers 938:955 No mineralized colonies were observed in BSP-/- cultures, along with little/no expression of either osteogenic markers or SIBLING proteins MEPE or DMP1. 25710686 1 22 theme N-linked 187:194 arg1 family 220:225 the "small integrin-binding ligand N-linked glycoprotein" (SIBLING) family 152:225 the "small integrin-binding ligand N-linked glycoprotein" (SIBLING) family 152:225 Bone sialoprotein (BSP) belongs to the "small integrin-binding ligand N-linked glycoprotein" (SIBLING) family, whose members interact with bone cells and bone mineral. 25710686 10 23 theme bone 1797:1800 arg1 microenvironment 1802:1817 The BSP knockout bone microenvironment 1780:1817 The BSP knockout bone microenvironment 1780:1817 The BSP knockout bone microenvironment may alter the proliferation/cell fate of early osteoprogenitors. 25710686 6 24 theme BSP-/- 1059:1064 arg1 culture 1066:1072 standard density BSP-/- culture 1042:1072 standard density BSP-/- culture 1042:1072 Osteopontin (OPN) is the only SIBLING expressed in standard density BSP-/- culture, at higher levels than in wild type in early culture times. 25710686 5 25 theme little/no 907:915 arg1 expression 917:926 little/no expression 907:926 little/no expression of either osteogenic markers or SIBLING proteins MEPE or DMP1 907:988 No mineralized colonies were observed in BSP-/- cultures, along with little/no expression of either osteogenic markers or SIBLING proteins MEPE or DMP1. 25710686 1 26 theme Bone 117:120 arg1 BSP 136:138 BSP 136:138 BSP 136:138 Bone sialoprotein (BSP) belongs to the "small integrin-binding ligand N-linked glycoprotein" (SIBLING) family, whose members interact with bone cells and bone mineral. 25710686 1 26 theme Bone 117:120 arg1 sialoprotein 122:133 Bone sialoprotein 117:133 Bone sialoprotein (BSP) 117:139 Bone sialoprotein (BSP) belongs to the "small integrin-binding ligand N-linked glycoprotein" (SIBLING) family, whose members interact with bone cells and bone mineral. 25710686 4 27 theme osteoprogenitors 820:835 arg1 number 810:815 a lower number 802:815 a lower number of osteoprogenitors 802:835 MCC BSP-/- cultures exhibit fewer fibroblast (CFU-F), preosteoblast (CFU-ALP) and osteoblast colonies (bone nodules) than wild type, indicative of a lower number of osteoprogenitors. 25710686 6 28 theme standard 1042:1049 arg1 culture 1066:1072 standard density BSP-/- culture 1042:1072 standard density BSP-/- culture 1042:1072 Osteopontin (OPN) is the only SIBLING expressed in standard density BSP-/- culture, at higher levels than in wild type in early culture times. 25710686 3 29 theme BSP-/- 534:539 arg1 mice 541:544 BSP-/- mice 534:544 BSP-/- mice 534:544 Because baseline bone formation activity is constitutively lower in BSP-/- mice, we studied the impact of the absence of BSP on in vitro osteogenesis in mouse calvaria cell (MCC) cultures. 25710686 2 30 theme type 410:413 arg1 littermates 424:434 wild type (BSP+/+) littermates 405:434 wild type (BSP+/+) littermates 405:434 BSP is strongly expressed in bone and we previously showed that BSP knockout (BSP-/-) mice have a higher bone mass than wild type (BSP+/+) littermates, with lower bone remodelling. 25710686 9 31 with consistent 1680:1689 arg1 levels 1737:1742 the low levels 1729:1742 the low levels of bone formation observed in vivo 1729:1777 Altogether, we found that BSP regulates mouse calvaria osteoblast cell clonogenicity, differentiation and activity in vitro in a cell density dependent manner, consistent with the effective skeletogenesis but the low levels of bone formation observed in vivo. 25710686 9 31 with consistent 1680:1689 arg1 skeletogenesis 1710:1723 the effective skeletogenesis 1696:1723 the effective skeletogenesis 1696:1723 Altogether, we found that BSP regulates mouse calvaria osteoblast cell clonogenicity, differentiation and activity in vitro in a cell density dependent manner, consistent with the effective skeletogenesis but the low levels of bone formation observed in vivo. 25710686 0 32 theme knockout 58:65 arg1 cultures 81:88 bone sialoprotein (BSP) knockout calvaria cell cultures 34:88 bone sialoprotein (BSP) knockout calvaria cell cultures 34:88 The impairment of osteogenesis in bone sialoprotein (BSP) knockout calvaria cell cultures is cell density dependent. 25710686 6 33 theme density 1051:1057 arg1 culture 1066:1072 standard density BSP-/- culture 1042:1072 standard density BSP-/- culture 1042:1072 Osteopontin (OPN) is the only SIBLING expressed in standard density BSP-/- culture, at higher levels than in wild type in early culture times. 25710686 10 34 theme early 1860:1864 arg1 osteoprogenitors 1866:1881 early osteoprogenitors 1860:1881 early osteoprogenitors 1860:1881 The BSP knockout bone microenvironment may alter the proliferation/cell fate of early osteoprogenitors. 25710686 0 35 theme cell 76:79 arg1 cultures 81:88 bone sialoprotein (BSP) knockout calvaria cell cultures 34:88 bone sialoprotein (BSP) knockout calvaria cell cultures 34:88 The impairment of osteogenesis in bone sialoprotein (BSP) knockout calvaria cell cultures is cell density dependent. 25710686 4 36 theme number 810:815 arg1 indicative 788:797 indicative 788:797 indicative 788:797 MCC BSP-/- cultures exhibit fewer fibroblast (CFU-F), preosteoblast (CFU-ALP) and osteoblast colonies (bone nodules) than wild type, indicative of a lower number of osteoprogenitors. 25710686 8 37 theme OPN 1335:1337 arg1 expression 1339:1348 OPN expression 1335:1348 OPN expression 1335:1348 OPN expression and amount are further increased in high density BSP-/- cultures, while PHEX and CatB expression are differentiatlly regulated in a manner that may favor mineralization. 25710686 4 38 theme BSP-/- 659:664 arg1 cultures 666:673 MCC BSP-/- cultures 655:673 MCC BSP-/- cultures 655:673 MCC BSP-/- cultures exhibit fewer fibroblast (CFU-F), preosteoblast (CFU-ALP) and osteoblast colonies (bone nodules) than wild type, indicative of a lower number of osteoprogenitors. 25710686 5 39 theme proteins 968:975 arg1 expression 917:926 little/no expression 907:926 little/no expression of either osteogenic markers or SIBLING proteins MEPE or DMP1 907:988 No mineralized colonies were observed in BSP-/- cultures, along with little/no expression of either osteogenic markers or SIBLING proteins MEPE or DMP1. 25710686 9 40 theme mouse 1560:1564 arg1 clonogenicity 1591:1603 mouse calvaria osteoblast cell clonogenicity 1560:1603 mouse calvaria osteoblast cell clonogenicity 1560:1603 Altogether, we found that BSP regulates mouse calvaria osteoblast cell clonogenicity, differentiation and activity in vitro in a cell density dependent manner, consistent with the effective skeletogenesis but the low levels of bone formation observed in vivo. 25710686 2 41 theme BSP-/- 363:368 arg1 mice 371:374 BSP knockout (BSP-/-) mice 349:374 BSP knockout (BSP-/-) mice 349:374 BSP is strongly expressed in bone and we previously showed that BSP knockout (BSP-/-) mice have a higher bone mass than wild type (BSP+/+) littermates, with lower bone remodelling. 25710686 3 42 dep in 594:595 arg1 vitro 597:601 vitro 597:601 vitro 597:601 Because baseline bone formation activity is constitutively lower in BSP-/- mice, we studied the impact of the absence of BSP on in vitro osteogenesis in mouse calvaria cell (MCC) cultures. 25710686 7 43 theme higher 1137:1142 arg1 density 1152:1158 higher plating density 1137:1158 higher plating density 1137:1158 At higher plating density, the effects of the absence of BSP were partly rescued, with resumed expression of osteoblast markers and cognate SIBLING proteins, and mineralization of the mutant cultures. 25710686 2 44 theme knockout 353:360 arg1 mice 371:374 BSP knockout (BSP-/-) mice 349:374 BSP knockout (BSP-/-) mice 349:374 BSP is strongly expressed in bone and we previously showed that BSP knockout (BSP-/-) mice have a higher bone mass than wild type (BSP+/+) littermates, with lower bone remodelling. 25710686 5 45 theme BSP-/- 879:884 arg1 cultures 886:893 BSP-/- cultures 879:893 BSP-/- cultures 879:893 No mineralized colonies were observed in BSP-/- cultures, along with little/no expression of either osteogenic markers or SIBLING proteins MEPE or DMP1. 25710686 2 46 theme bone 390:393 arg1 mass 395:398 a higher bone mass 381:398 a higher bone mass than wild type (BSP+/+) littermates 381:434 BSP is strongly expressed in bone and we previously showed that BSP knockout (BSP-/-) mice have a higher bone mass than wild type (BSP+/+) littermates, with lower bone remodelling. 25710686 8 47 theme density 1391:1397 arg1 cultures 1406:1413 high density BSP-/- cultures 1386:1413 high density BSP-/- cultures 1386:1413 OPN expression and amount are further increased in high density BSP-/- cultures, while PHEX and CatB expression are differentiatlly regulated in a manner that may favor mineralization. 25710686 0 48 theme sialoprotein 39:50 arg1 cultures 81:88 bone sialoprotein (BSP) knockout calvaria cell cultures 34:88 bone sialoprotein (BSP) knockout calvaria cell cultures 34:88 The impairment of osteogenesis in bone sialoprotein (BSP) knockout calvaria cell cultures is cell density dependent. 25710686 7 49 theme cultures 1325:1332 arg1 mineralization 1296:1309 mineralization 1296:1309 mineralization of the mutant cultures 1296:1332 At higher plating density, the effects of the absence of BSP were partly rescued, with resumed expression of osteoblast markers and cognate SIBLING proteins, and mineralization of the mutant cultures. 25710686 7 49 theme cultures 1325:1332 arg1 expression 1229:1238 resumed expression 1221:1238 resumed expression of osteoblast markers and cognate SIBLING proteins 1221:1289 At higher plating density, the effects of the absence of BSP were partly rescued, with resumed expression of osteoblast markers and cognate SIBLING proteins, and mineralization of the mutant cultures. 25710686 8 50 theme BSP-/- 1399:1404 arg1 cultures 1406:1413 high density BSP-/- cultures 1386:1413 high density BSP-/- cultures 1386:1413 OPN expression and amount are further increased in high density BSP-/- cultures, while PHEX and CatB expression are differentiatlly regulated in a manner that may favor mineralization. 25710686 1 51 theme glycoprotein 196:207 arg1 family 220:225 the "small integrin-binding ligand N-linked glycoprotein" (SIBLING) family 152:225 the "small integrin-binding ligand N-linked glycoprotein" (SIBLING) family 152:225 Bone sialoprotein (BSP) belongs to the "small integrin-binding ligand N-linked glycoprotein" (SIBLING) family, whose members interact with bone cells and bone mineral. 25710686 2 52 theme BSP 349:351 arg1 mice 371:374 BSP knockout (BSP-/-) mice 349:374 BSP knockout (BSP-/-) mice 349:374 BSP is strongly expressed in bone and we previously showed that BSP knockout (BSP-/-) mice have a higher bone mass than wild type (BSP+/+) littermates, with lower bone remodelling. 25710686 9 53 theme density 1654:1660 arg1 manner 1672:1677 a cell density dependent manner 1647:1677 a cell density dependent manner 1647:1677 Altogether, we found that BSP regulates mouse calvaria osteoblast cell clonogenicity, differentiation and activity in vitro in a cell density dependent manner, consistent with the effective skeletogenesis but the low levels of bone formation observed in vivo. 25710686 8 54 theme high 1386:1389 arg1 cultures 1406:1413 high density BSP-/- cultures 1386:1413 high density BSP-/- cultures 1386:1413 OPN expression and amount are further increased in high density BSP-/- cultures, while PHEX and CatB expression are differentiatlly regulated in a manner that may favor mineralization. 25710686 9 55 theme osteoblast 1575:1584 arg1 clonogenicity 1591:1603 mouse calvaria osteoblast cell clonogenicity 1560:1603 mouse calvaria osteoblast cell clonogenicity 1560:1603 Altogether, we found that BSP regulates mouse calvaria osteoblast cell clonogenicity, differentiation and activity in vitro in a cell density dependent manner, consistent with the effective skeletogenesis but the low levels of bone formation observed in vivo. 25710686 6 56 theme culture 1119:1125 arg1 times 1127:1131 early culture times 1113:1131 early culture times 1113:1131 Osteopontin (OPN) is the only SIBLING expressed in standard density BSP-/- culture, at higher levels than in wild type in early culture times. 25710686 8 57 theme CatB 1431:1434 arg1 expression 1436:1445 CatB expression 1431:1445 CatB expression 1431:1445 OPN expression and amount are further increased in high density BSP-/- cultures, while PHEX and CatB expression are differentiatlly regulated in a manner that may favor mineralization. 25710686 5 58 located observed 867:874 arg1 cultures 886:893 BSP-/- cultures 879:893 BSP-/- cultures 879:893 No mineralized colonies were observed in BSP-/- cultures, along with little/no expression of either osteogenic markers or SIBLING proteins MEPE or DMP1. 25710686 5 58 located observed 867:874 arg2 colonies 853:860 No mineralized colonies 838:860 No mineralized colonies 838:860 No mineralized colonies were observed in BSP-/- cultures, along with little/no expression of either osteogenic markers or SIBLING proteins MEPE or DMP1. 25710686 7 59 theme SIBLING 1274:1280 arg1 proteins 1282:1289 cognate SIBLING proteins 1266:1289 cognate SIBLING proteins 1266:1289 At higher plating density, the effects of the absence of BSP were partly rescued, with resumed expression of osteoblast markers and cognate SIBLING proteins, and mineralization of the mutant cultures. 25710686 7 60 theme markers 1254:1260 arg1 mineralization 1296:1309 mineralization 1296:1309 mineralization of the mutant cultures 1296:1332 At higher plating density, the effects of the absence of BSP were partly rescued, with resumed expression of osteoblast markers and cognate SIBLING proteins, and mineralization of the mutant cultures. 25710686 7 60 theme markers 1254:1260 arg1 expression 1229:1238 resumed expression 1221:1238 resumed expression of osteoblast markers and cognate SIBLING proteins 1221:1289 At higher plating density, the effects of the absence of BSP were partly rescued, with resumed expression of osteoblast markers and cognate SIBLING proteins, and mineralization of the mutant cultures. 25710686 3 61 theme calvaria 625:632 arg1 cultures 645:652 mouse calvaria cell (MCC) cultures 619:652 mouse calvaria cell (MCC) cultures 619:652 Because baseline bone formation activity is constitutively lower in BSP-/- mice, we studied the impact of the absence of BSP on in vitro osteogenesis in mouse calvaria cell (MCC) cultures. 25710686 6 62 theme wild 1100:1103 arg1 type 1105:1108 wild type 1100:1108 wild type in early culture times 1100:1131 Osteopontin (OPN) is the only SIBLING expressed in standard density BSP-/- culture, at higher levels than in wild type in early culture times. 25710686 9 63 theme dependent 1662:1670 arg1 manner 1672:1677 a cell density dependent manner 1647:1677 a cell density dependent manner 1647:1677 Altogether, we found that BSP regulates mouse calvaria osteoblast cell clonogenicity, differentiation and activity in vitro in a cell density dependent manner, consistent with the effective skeletogenesis but the low levels of bone formation observed in vivo. 25710686 3 64 from osteogenesis 603:614 arg1 cultures 645:652 mouse calvaria cell (MCC) cultures 619:652 mouse calvaria cell (MCC) cultures 619:652 Because baseline bone formation activity is constitutively lower in BSP-/- mice, we studied the impact of the absence of BSP on in vitro osteogenesis in mouse calvaria cell (MCC) cultures. 25710686 9 65 theme cell 1586:1589 arg1 clonogenicity 1591:1603 mouse calvaria osteoblast cell clonogenicity 1560:1603 mouse calvaria osteoblast cell clonogenicity 1560:1603 Altogether, we found that BSP regulates mouse calvaria osteoblast cell clonogenicity, differentiation and activity in vitro in a cell density dependent manner, consistent with the effective skeletogenesis but the low levels of bone formation observed in vivo. 25710686 10 66 theme BSP 1784:1786 arg1 microenvironment 1802:1817 The BSP knockout bone microenvironment 1780:1817 The BSP knockout bone microenvironment 1780:1817 The BSP knockout bone microenvironment may alter the proliferation/cell fate of early osteoprogenitors. 25710686 3 67 theme bone 483:486 arg1 formation 488:496 baseline bone formation 474:496 baseline bone formation activity 474:505 Because baseline bone formation activity is constitutively lower in BSP-/- mice, we studied the impact of the absence of BSP on in vitro osteogenesis in mouse calvaria cell (MCC) cultures. 25710686 7 68 theme resumed 1221:1227 arg1 expression 1229:1238 resumed expression 1221:1238 resumed expression of osteoblast markers and cognate SIBLING proteins 1221:1289 At higher plating density, the effects of the absence of BSP were partly rescued, with resumed expression of osteoblast markers and cognate SIBLING proteins, and mineralization of the mutant cultures. 25710686 9 69 theme bone 1747:1750 arg1 formation 1752:1760 bone formation 1747:1760 bone formation 1747:1760 Altogether, we found that BSP regulates mouse calvaria osteoblast cell clonogenicity, differentiation and activity in vitro in a cell density dependent manner, consistent with the effective skeletogenesis but the low levels of bone formation observed in vivo. 25710686 1 70 theme small 157:161 arg1 family 220:225 the "small integrin-binding ligand N-linked glycoprotein" (SIBLING) family 152:225 the "small integrin-binding ligand N-linked glycoprotein" (SIBLING) family 152:225 Bone sialoprotein (BSP) belongs to the "small integrin-binding ligand N-linked glycoprotein" (SIBLING) family, whose members interact with bone cells and bone mineral. 25710686 4 71 theme wild 777:780 arg1 type 782:785 wild type 777:785 wild type 777:785 MCC BSP-/- cultures exhibit fewer fibroblast (CFU-F), preosteoblast (CFU-ALP) and osteoblast colonies (bone nodules) than wild type, indicative of a lower number of osteoprogenitors. 25710686 1 72 theme ligand 180:185 arg1 family 220:225 the "small integrin-binding ligand N-linked glycoprotein" (SIBLING) family 152:225 the "small integrin-binding ligand N-linked glycoprotein" (SIBLING) family 152:225 Bone sialoprotein (BSP) belongs to the "small integrin-binding ligand N-linked glycoprotein" (SIBLING) family, whose members interact with bone cells and bone mineral. 25710686 2 73 theme lower 442:446 arg1 remodelling 453:463 lower bone remodelling 442:463 lower bone remodelling 442:463 BSP is strongly expressed in bone and we previously showed that BSP knockout (BSP-/-) mice have a higher bone mass than wild type (BSP+/+) littermates, with lower bone remodelling. 25710686 5 74 theme markers 949:955 arg1 expression 917:926 little/no expression 907:926 little/no expression of either osteogenic markers or SIBLING proteins MEPE or DMP1 907:988 No mineralized colonies were observed in BSP-/- cultures, along with little/no expression of either osteogenic markers or SIBLING proteins MEPE or DMP1. 25710686 4 75 theme bone 758:761 arg1 colonies 748:755 osteoblast colonies 737:755 osteoblast colonies (bone nodules) 737:770 MCC BSP-/- cultures exhibit fewer fibroblast (CFU-F), preosteoblast (CFU-ALP) and osteoblast colonies (bone nodules) than wild type, indicative of a lower number of osteoprogenitors. 25710686 4 75 theme bone 758:761 arg1 nodules 763:769 bone nodules 758:769 bone nodules 758:769 MCC BSP-/- cultures exhibit fewer fibroblast (CFU-F), preosteoblast (CFU-ALP) and osteoblast colonies (bone nodules) than wild type, indicative of a lower number of osteoprogenitors. 25710686 7 76 theme BSP 1191:1193 arg1 absence 1180:1186 the absence 1176:1186 the absence of BSP 1176:1193 At higher plating density, the effects of the absence of BSP were partly rescued, with resumed expression of osteoblast markers and cognate SIBLING proteins, and mineralization of the mutant cultures. 25710686 10 77 theme knockout 1788:1795 arg1 microenvironment 1802:1817 The BSP knockout bone microenvironment 1780:1817 The BSP knockout bone microenvironment 1780:1817 The BSP knockout bone microenvironment may alter the proliferation/cell fate of early osteoprogenitors. 25710686 7 78 theme absence 1180:1186 arg1 effects 1165:1171 the effects 1161:1171 the effects of the absence of BSP 1161:1193 At higher plating density, the effects of the absence of BSP were partly rescued, with resumed expression of osteoblast markers and cognate SIBLING proteins, and mineralization of the mutant cultures. 25710686 10 79 theme proliferation/cell 1833:1850 arg1 fate 1852:1855 the proliferation/cell fate 1829:1855 the proliferation/cell fate of early osteoprogenitors 1829:1881 The BSP knockout bone microenvironment may alter the proliferation/cell fate of early osteoprogenitors. 25710686 9 80 theme calvaria 1566:1573 arg1 clonogenicity 1591:1603 mouse calvaria osteoblast cell clonogenicity 1560:1603 mouse calvaria osteoblast cell clonogenicity 1560:1603 Altogether, we found that BSP regulates mouse calvaria osteoblast cell clonogenicity, differentiation and activity in vitro in a cell density dependent manner, consistent with the effective skeletogenesis but the low levels of bone formation observed in vivo. 25710686 0 81 theme calvaria 67:74 arg1 cultures 81:88 bone sialoprotein (BSP) knockout calvaria cell cultures 34:88 bone sialoprotein (BSP) knockout calvaria cell cultures 34:88 The impairment of osteogenesis in bone sialoprotein (BSP) knockout calvaria cell cultures is cell density dependent. 25710686 2 82 theme wild 405:408 arg1 BSP+/+ 416:421 BSP+/+ 416:421 BSP+/+ 416:421 BSP is strongly expressed in bone and we previously showed that BSP knockout (BSP-/-) mice have a higher bone mass than wild type (BSP+/+) littermates, with lower bone remodelling. 25710686 2 82 theme wild 405:408 arg1 type 410:413 wild type 405:413 wild type (BSP+/+) littermates 405:434 BSP is strongly expressed in bone and we previously showed that BSP knockout (BSP-/-) mice have a higher bone mass than wild type (BSP+/+) littermates, with lower bone remodelling. 25710686 0 83 from impairment 4:13 arg1 cultures 81:88 bone sialoprotein (BSP) knockout calvaria cell cultures 34:88 bone sialoprotein (BSP) knockout calvaria cell cultures 34:88 The impairment of osteogenesis in bone sialoprotein (BSP) knockout calvaria cell cultures is cell density dependent. 25710686 1 84 link N-linked 187:194 arg1 family 220:225 the "small integrin-binding ligand N-linked glycoprotein" (SIBLING) family 152:225 the "small integrin-binding ligand N-linked glycoprotein" (SIBLING) family 152:225 Bone sialoprotein (BSP) belongs to the "small integrin-binding ligand N-linked glycoprotein" (SIBLING) family, whose members interact with bone cells and bone mineral. 25710686 10 85 theme osteoprogenitors 1866:1881 arg1 fate 1852:1855 the proliferation/cell fate 1829:1855 the proliferation/cell fate of early osteoprogenitors 1829:1881 The BSP knockout bone microenvironment may alter the proliferation/cell fate of early osteoprogenitors. 25710686 1 86 gly glycoprotein 196:207 arg1 glycoprotein 196:207 the "small integrin-binding ligand N-linked glycoprotein" (SIBLING) family 152:225 the "small integrin-binding ligand N-linked glycoprotein" (SIBLING) family 152:225 Bone sialoprotein (BSP) belongs to the "small integrin-binding ligand N-linked glycoprotein" (SIBLING) family, whose members interact with bone cells and bone mineral. 25710686 5 87 theme SIBLING 960:966 arg1 proteins 968:975 SIBLING proteins MEPE or DMP1 960:988 SIBLING proteins MEPE or DMP1 960:988 No mineralized colonies were observed in BSP-/- cultures, along with little/no expression of either osteogenic markers or SIBLING proteins MEPE or DMP1. 25710686 5 87 theme SIBLING 960:966 arg1 DMP1 985:988 DMP1 985:988 DMP1 985:988 No mineralized colonies were observed in BSP-/- cultures, along with little/no expression of either osteogenic markers or SIBLING proteins MEPE or DMP1. 25710686 5 87 theme SIBLING 960:966 arg1 MEPE 977:980 MEPE 977:980 MEPE 977:980 No mineralized colonies were observed in BSP-/- cultures, along with little/no expression of either osteogenic markers or SIBLING proteins MEPE or DMP1. 25710686 4 88 theme lower 804:808 arg1 number 810:815 a lower number 802:815 a lower number of osteoprogenitors 802:835 MCC BSP-/- cultures exhibit fewer fibroblast (CFU-F), preosteoblast (CFU-ALP) and osteoblast colonies (bone nodules) than wild type, indicative of a lower number of osteoprogenitors. 25710686 4 89 theme MCC 655:657 arg1 cultures 666:673 MCC BSP-/- cultures 655:673 MCC BSP-/- cultures 655:673 MCC BSP-/- cultures exhibit fewer fibroblast (CFU-F), preosteoblast (CFU-ALP) and osteoblast colonies (bone nodules) than wild type, indicative of a lower number of osteoprogenitors. 25710686 7 90 theme plating 1144:1150 arg1 density 1152:1158 higher plating density 1137:1158 higher plating density 1137:1158 At higher plating density, the effects of the absence of BSP were partly rescued, with resumed expression of osteoblast markers and cognate SIBLING proteins, and mineralization of the mutant cultures. 25710686 2 91 theme bone 448:451 arg1 remodelling 453:463 lower bone remodelling 442:463 lower bone remodelling 442:463 BSP is strongly expressed in bone and we previously showed that BSP knockout (BSP-/-) mice have a higher bone mass than wild type (BSP+/+) littermates, with lower bone remodelling. 25710686 0 92 theme osteogenesis 18:29 arg1 impairment 4:13 The impairment 0:13 The impairment of osteogenesis in bone sialoprotein (BSP) knockout calvaria cell cultures 0:88 The impairment of osteogenesis in bone sialoprotein (BSP) knockout calvaria cell cultures is cell density dependent. 25710686 0 92 theme osteogenesis 18:29 arg1 dependent 106:114 dependent 106:114 dependent 106:114 The impairment of osteogenesis in bone sialoprotein (BSP) knockout calvaria cell cultures is cell density dependent. 25710686 0 93 theme bone 34:37 arg1 BSP 53:55 BSP 53:55 BSP 53:55 The impairment of osteogenesis in bone sialoprotein (BSP) knockout calvaria cell cultures is cell density dependent. 25710686 0 93 theme bone 34:37 arg1 sialoprotein 39:50 bone sialoprotein 34:50 bone sialoprotein (BSP) knockout calvaria cell cultures 34:88 The impairment of osteogenesis in bone sialoprotein (BSP) knockout calvaria cell cultures is cell density dependent. 25710686 1 94 theme bone 256:259 arg1 cells 261:265 bone cells 256:265 bone cells 256:265 Bone sialoprotein (BSP) belongs to the "small integrin-binding ligand N-linked glycoprotein" (SIBLING) family, whose members interact with bone cells and bone mineral. 25710686 9 95 theme cell 1649:1652 arg1 manner 1672:1677 a cell density dependent manner 1647:1677 a cell density dependent manner 1647:1677 Altogether, we found that BSP regulates mouse calvaria osteoblast cell clonogenicity, differentiation and activity in vitro in a cell density dependent manner, consistent with the effective skeletogenesis but the low levels of bone formation observed in vivo. 25710686 5 96 dep proteins 968:975 arg1 proteins 968:975 SIBLING proteins MEPE or DMP1 960:988 SIBLING proteins MEPE or DMP1 960:988 No mineralized colonies were observed in BSP-/- cultures, along with little/no expression of either osteogenic markers or SIBLING proteins MEPE or DMP1. 25710686 5 96 dep proteins 968:975 arg1 DMP1 985:988 DMP1 985:988 DMP1 985:988 No mineralized colonies were observed in BSP-/- cultures, along with little/no expression of either osteogenic markers or SIBLING proteins MEPE or DMP1. 25710686 5 96 dep proteins 968:975 arg1 MEPE 977:980 MEPE 977:980 MEPE 977:980 No mineralized colonies were observed in BSP-/- cultures, along with little/no expression of either osteogenic markers or SIBLING proteins MEPE or DMP1. 25710686 1 97 theme " 208:208 arg1 family 220:225 the "small integrin-binding ligand N-linked glycoprotein" (SIBLING) family 152:225 the "small integrin-binding ligand N-linked glycoprotein" (SIBLING) family 152:225 Bone sialoprotein (BSP) belongs to the "small integrin-binding ligand N-linked glycoprotein" (SIBLING) family, whose members interact with bone cells and bone mineral. 25710686 2 98 theme higher 383:388 arg1 mass 395:398 a higher bone mass 381:398 a higher bone mass than wild type (BSP+/+) littermates 381:434 BSP is strongly expressed in bone and we previously showed that BSP knockout (BSP-/-) mice have a higher bone mass than wild type (BSP+/+) littermates, with lower bone remodelling. 25710686 3 99 theme absence 576:582 arg1 impact 562:567 the impact 558:567 the impact of the absence of BSP on in vitro osteogenesis in mouse calvaria cell (MCC) cultures 558:652 Because baseline bone formation activity is constitutively lower in BSP-/- mice, we studied the impact of the absence of BSP on in vitro osteogenesis in mouse calvaria cell (MCC) cultures. 25710686 5 100 theme mineralized 841:851 arg1 colonies 853:860 No mineralized colonies 838:860 No mineralized colonies 838:860 No mineralized colonies were observed in BSP-/- cultures, along with little/no expression of either osteogenic markers or SIBLING proteins MEPE or DMP1. 25710686 6 101 from type 1105:1108 arg1 times 1127:1131 early culture times 1113:1131 early culture times 1113:1131 Osteopontin (OPN) is the only SIBLING expressed in standard density BSP-/- culture, at higher levels than in wild type in early culture times. 25710686 7 102 theme mutant 1318:1323 arg1 cultures 1325:1332 the mutant cultures 1314:1332 the mutant cultures 1314:1332 At higher plating density, the effects of the absence of BSP were partly rescued, with resumed expression of osteoblast markers and cognate SIBLING proteins, and mineralization of the mutant cultures. 25710686 3 103 theme in 594:595 arg1 osteogenesis 603:614 in vitro osteogenesis 594:614 in vitro osteogenesis in mouse calvaria cell (MCC) cultures 594:652 Because baseline bone formation activity is constitutively lower in BSP-/- mice, we studied the impact of the absence of BSP on in vitro osteogenesis in mouse calvaria cell (MCC) cultures. 25710686 4 104 theme fewer 683:687 arg1 CFU-F 701:705 CFU-F 701:705 CFU-F 701:705 MCC BSP-/- cultures exhibit fewer fibroblast (CFU-F), preosteoblast (CFU-ALP) and osteoblast colonies (bone nodules) than wild type, indicative of a lower number of osteoprogenitors. 25710686 4 104 theme fewer 683:687 arg1 fibroblast 689:698 fewer fibroblast 683:698 fewer fibroblast (CFU-F) 683:706 MCC BSP-/- cultures exhibit fewer fibroblast (CFU-F), preosteoblast (CFU-ALP) and osteoblast colonies (bone nodules) than wild type, indicative of a lower number of osteoprogenitors. 25710686 1 105 theme SIBLING 211:217 arg1 family 220:225 the "small integrin-binding ligand N-linked glycoprotein" (SIBLING) family 152:225 the "small integrin-binding ligand N-linked glycoprotein" (SIBLING) family 152:225 Bone sialoprotein (BSP) belongs to the "small integrin-binding ligand N-linked glycoprotein" (SIBLING) family, whose members interact with bone cells and bone mineral. 25131991 6 0 theme pathologies 1050:1060 arg1 infection 1077:1085 viral infection 1071:1085 viral infection 1071:1085 Inhibitors of GII are used to inhibit cell proliferation and migration in a variety of different pathologies, such as viral infection, cancer, and diabetes. 25131991 6 0 theme pathologies 1050:1060 arg1 cancer 1088:1093 cancer 1088:1093 cancer 1088:1093 Inhibitors of GII are used to inhibit cell proliferation and migration in a variety of different pathologies, such as viral infection, cancer, and diabetes. 25131991 6 0 theme pathologies 1050:1060 arg1 diabetes 1100:1107 diabetes 1100:1107 diabetes 1100:1107 Inhibitors of GII are used to inhibit cell proliferation and migration in a variety of different pathologies, such as viral infection, cancer, and diabetes. 25131991 6 0 theme pathologies 1050:1060 arg1 variety 1029:1035 a variety 1027:1035 a variety of different pathologies, such as viral infection, cancer, and diabetes 1027:1107 Inhibitors of GII are used to inhibit cell proliferation and migration in a variety of different pathologies, such as viral infection, cancer, and diabetes. 25131991 6 0 theme pathologies 1050:1060 arg1 pathologies 1050:1060 different pathologies 1040:1060 different pathologies 1040:1060 Inhibitors of GII are used to inhibit cell proliferation and migration in a variety of different pathologies, such as viral infection, cancer, and diabetes. 25131991 3 1 theme GIIβ 613:616 arg1 subunit 618:624 the HDEL-containing GIIβ subunit 593:624 the HDEL-containing GIIβ subunit 593:624 The soluble GIIα subunit is retained in the ER through its interaction with the HDEL-containing GIIβ subunit. 25131991 10 2 theme polypeptide 1598:1608 arg1 levels 1610:1615 GIIα polypeptide levels 1593:1615 GIIα polypeptide levels in whole brain 1593:1630 GIIα polypeptide levels in whole brain were comparable to those in spleen. 25131991 5 3 from invasion 922:929 arg1 migration 848:856 neuronal migration 839:856 neuronal migration 839:856 Alterations in N-glycosylation lead to abnormalities in neuronal migration and mental retardation, various neurodegenerative diseases, and invasion of malignant gliomas. 25131991 5 3 from invasion 922:929 arg1 retardation 869:879 mental retardation 862:879 mental retardation 862:879 Alterations in N-glycosylation lead to abnormalities in neuronal migration and mental retardation, various neurodegenerative diseases, and invasion of malignant gliomas. 25131991 1 4 theme nascent 201:207 arg1 glycoproteins 209:221 nascent glycoproteins 201:221 nascent glycoproteins 201:221 α-Glucosidase II (GII), a resident of endoplasmic reticulum (ER) and an important enzyme in the folding of nascent glycoproteins, is heterodimeric, consisting of α (GIIα) and β (GIIβ) subunits. 25131991 3 5 with interaction 576:586 arg1 subunit 618:624 the HDEL-containing GIIβ subunit 593:624 the HDEL-containing GIIβ subunit 593:624 The soluble GIIα subunit is retained in the ER through its interaction with the HDEL-containing GIIβ subunit. 25131991 6 6 used used 975:978 arg2 Inhibitors 953:962 Inhibitors 953:962 Inhibitors of GII 953:969 Inhibitors of GII are used to inhibit cell proliferation and migration in a variety of different pathologies, such as viral infection, cancer, and diabetes. 25131991 1 7 theme reticulum 144:152 arg1 resident 120:127 resident 120:127 resident 120:127 α-Glucosidase II (GII), a resident of endoplasmic reticulum (ER) and an important enzyme in the folding of nascent glycoproteins, is heterodimeric, consisting of α (GIIα) and β (GIIβ) subunits. 25131991 1 7 theme reticulum 144:152 arg1 α-Glucosidase 94:106 α-Glucosidase II 94:109 α-Glucosidase II (GII) 94:115 α-Glucosidase II (GII), a resident of endoplasmic reticulum (ER) and an important enzyme in the folding of nascent glycoproteins, is heterodimeric, consisting of α (GIIα) and β (GIIβ) subunits. 25131991 9 8 theme lowest 1569:1574 arg1 amount 1576:1581 the lowest amount 1565:1581 the lowest amount in heart 1565:1590 By using this antibody, we showed that the GIIα protein is highly expressed in testis, kidney, and lung, with the lowest amount in heart. 25131991 7 9 from drugs 1156:1160 arg1 function 1192:1199 brain function 1186:1199 brain function 1186:1199 Despite the widespread use of GIIα inhibitory drugs and the role of GIIα in brain function, little is known about its expression in brain and other tissues. 25131991 9 10 from amount 1576:1581 arg1 heart 1586:1590 heart 1586:1590 heart 1586:1590 By using this antibody, we showed that the GIIα protein is highly expressed in testis, kidney, and lung, with the lowest amount in heart. 25131991 2 11 link N-linked 466:473 arg1 folding 508:514 N-linked oligosaccharide-mediated protein folding 466:514 N-linked oligosaccharide-mediated protein folding 466:514 The catalytic GIIα subunit, with the help of mannose 6-phosphate receptor homology domain of GIIβ, sequentially hydrolyzes two α1-3-linked glucose residues in the second step of N-linked oligosaccharide-mediated protein folding. 25131991 7 12 theme GIIα 1178:1181 arg1 drugs 1156:1160 GIIα inhibitory drugs 1140:1160 GIIα inhibitory drugs 1140:1160 Despite the widespread use of GIIα inhibitory drugs and the role of GIIα in brain function, little is known about its expression in brain and other tissues. 25131991 7 12 theme GIIα 1178:1181 arg1 role 1170:1173 the role 1166:1173 the role of GIIα in brain function 1166:1199 Despite the widespread use of GIIα inhibitory drugs and the role of GIIα in brain function, little is known about its expression in brain and other tissues. 25131991 2 13 theme second 451:456 arg1 step 458:461 the second step 447:461 the second step of N-linked oligosaccharide-mediated protein folding 447:514 The catalytic GIIα subunit, with the help of mannose 6-phosphate receptor homology domain of GIIβ, sequentially hydrolyzes two α1-3-linked glucose residues in the second step of N-linked oligosaccharide-mediated protein folding. 25131991 11 14 theme GIIα 1700:1703 arg1 protein 1705:1711 GIIα protein 1700:1711 GIIα protein 1700:1711 However, a higher expression of GIIα protein was detected in the cerebral cortex, reflecting its continuous requirement in correct folding of cell surface proteins. 25131991 3 15 theme GIIα 529:532 arg1 subunit 534:540 The soluble GIIα subunit 517:540 The soluble GIIα subunit 517:540 The soluble GIIα subunit is retained in the ER through its interaction with the HDEL-containing GIIβ subunit. 25131991 5 16 from Alterations 783:793 arg1 N-glycosylation 798:812 N-glycosylation 798:812 N-glycosylation 798:812 Alterations in N-glycosylation lead to abnormalities in neuronal migration and mental retardation, various neurodegenerative diseases, and invasion of malignant gliomas. 25131991 1 17 theme important 166:174 arg1 enzyme 176:181 an important enzyme 163:181 an important enzyme in the folding of nascent glycoproteins 163:221 α-Glucosidase II (GII), a resident of endoplasmic reticulum (ER) and an important enzyme in the folding of nascent glycoproteins, is heterodimeric, consisting of α (GIIα) and β (GIIβ) subunits. 25131991 2 18 theme folding 508:514 arg1 step 458:461 the second step 447:461 the second step of N-linked oligosaccharide-mediated protein folding 447:514 The catalytic GIIα subunit, with the help of mannose 6-phosphate receptor homology domain of GIIβ, sequentially hydrolyzes two α1-3-linked glucose residues in the second step of N-linked oligosaccharide-mediated protein folding. 25131991 4 19 theme correct 647:653 arg1 folding 663:669 correct protein folding 647:669 correct protein folding 647:669 N-glycosylation and correct protein folding are crucial for protein stability and trafficking and cell surface expression of several proteins in the brain. 25131991 11 20 theme proteins 1823:1830 arg1 folding 1799:1805 correct folding 1791:1805 correct folding of cell surface proteins 1791:1830 However, a higher expression of GIIα protein was detected in the cerebral cortex, reflecting its continuous requirement in correct folding of cell surface proteins. 25131991 2 21 theme oligosaccharide-mediated 475:498 arg1 folding 508:514 N-linked oligosaccharide-mediated protein folding 466:514 N-linked oligosaccharide-mediated protein folding 466:514 The catalytic GIIα subunit, with the help of mannose 6-phosphate receptor homology domain of GIIβ, sequentially hydrolyzes two α1-3-linked glucose residues in the second step of N-linked oligosaccharide-mediated protein folding. 25131991 5 22 theme various 882:888 arg1 diseases 908:915 various neurodegenerative diseases 882:915 various neurodegenerative diseases 882:915 Alterations in N-glycosylation lead to abnormalities in neuronal migration and mental retardation, various neurodegenerative diseases, and invasion of malignant gliomas. 25131991 7 23 from role 1170:1173 arg1 function 1192:1199 brain function 1186:1199 brain function 1186:1199 Despite the widespread use of GIIα inhibitory drugs and the role of GIIα in brain function, little is known about its expression in brain and other tissues. 25131991 2 24 link α1-3-linked 415:425 arg1 residues 435:442 two α1-3-linked glucose residues 411:442 two α1-3-linked glucose residues 411:442 The catalytic GIIα subunit, with the help of mannose 6-phosphate receptor homology domain of GIIβ, sequentially hydrolyzes two α1-3-linked glucose residues in the second step of N-linked oligosaccharide-mediated protein folding. 25131991 7 25 theme role 1170:1173 arg1 use 1133:1135 the widespread use 1118:1135 the widespread use of GIIα inhibitory drugs and the role of GIIα in brain function 1118:1199 Despite the widespread use of GIIα inhibitory drugs and the role of GIIα in brain function, little is known about its expression in brain and other tissues. 25131991 0 26 theme α-subunit 14:22 arg1 Expression 0:9 Expression 0:9 Expression of α-subunit of α-glucosidase II in adult mouse brain regions and selected organs. 0:92 Expression of α-subunit of α-glucosidase II in adult mouse brain regions and selected organs. 25131991 5 27 theme neuronal 839:846 arg1 migration 848:856 neuronal migration 839:856 neuronal migration 839:856 Alterations in N-glycosylation lead to abnormalities in neuronal migration and mental retardation, various neurodegenerative diseases, and invasion of malignant gliomas. 25131991 1 28 theme β 269:269 arg1 subunits 278:285 α (GIIα) and β (GIIβ) subunits 256:285 subunits 278:285 α-Glucosidase II (GII), a resident of endoplasmic reticulum (ER) and an important enzyme in the folding of nascent glycoproteins, is heterodimeric, consisting of α (GIIα) and β (GIIβ) subunits. 25131991 0 29 from Expression 0:9 arg1 regions 65:71 adult mouse brain regions 47:71 adult mouse brain regions 47:71 Expression of α-subunit of α-glucosidase II in adult mouse brain regions and selected organs. 25131991 0 29 from Expression 0:9 arg1 organs 86:91 selected organs 77:91 selected organs 77:91 Expression of α-subunit of α-glucosidase II in adult mouse brain regions and selected organs. 25131991 0 30 theme selected 77:84 arg1 organs 86:91 selected organs 77:91 selected organs 77:91 Expression of α-subunit of α-glucosidase II in adult mouse brain regions and selected organs. 25131991 1 31 theme GIIβ 272:275 arg1 subunits 278:285 α (GIIα) and β (GIIβ) subunits 256:285 subunits 278:285 α-Glucosidase II (GII), a resident of endoplasmic reticulum (ER) and an important enzyme in the folding of nascent glycoproteins, is heterodimeric, consisting of α (GIIα) and β (GIIβ) subunits. 25131991 2 32 theme glucose 427:433 arg1 residues 435:442 two α1-3-linked glucose residues 411:442 two α1-3-linked glucose residues 411:442 The catalytic GIIα subunit, with the help of mannose 6-phosphate receptor homology domain of GIIβ, sequentially hydrolyzes two α1-3-linked glucose residues in the second step of N-linked oligosaccharide-mediated protein folding. 25131991 5 33 theme gliomas 944:950 arg1 diseases 908:915 various neurodegenerative diseases 882:915 various neurodegenerative diseases 882:915 Alterations in N-glycosylation lead to abnormalities in neuronal migration and mental retardation, various neurodegenerative diseases, and invasion of malignant gliomas. 25131991 5 33 theme gliomas 944:950 arg1 invasion 922:929 invasion 922:929 invasion of malignant gliomas 922:950 Alterations in N-glycosylation lead to abnormalities in neuronal migration and mental retardation, various neurodegenerative diseases, and invasion of malignant gliomas. 25131991 5 33 theme gliomas 944:950 arg1 abnormalities 822:834 abnormalities 822:834 abnormalities in neuronal migration and mental retardation 822:879 Alterations in N-glycosylation lead to abnormalities in neuronal migration and mental retardation, various neurodegenerative diseases, and invasion of malignant gliomas. 25131991 7 34 theme other 1252:1256 arg1 tissues 1258:1264 other tissues 1252:1264 other tissues 1252:1264 Despite the widespread use of GIIα inhibitory drugs and the role of GIIα in brain function, little is known about its expression in brain and other tissues. 25131991 2 35 theme receptor 353:360 arg1 domain 371:376 mannose 6-phosphate receptor homology domain 333:376 mannose 6-phosphate receptor homology domain of GIIβ 333:384 The catalytic GIIα subunit, with the help of mannose 6-phosphate receptor homology domain of GIIβ, sequentially hydrolyzes two α1-3-linked glucose residues in the second step of N-linked oligosaccharide-mediated protein folding. 25131991 2 35 theme receptor 353:360 arg1 GIIβ 381:384 GIIβ 381:384 GIIβ 381:384 The catalytic GIIα subunit, with the help of mannose 6-phosphate receptor homology domain of GIIβ, sequentially hydrolyzes two α1-3-linked glucose residues in the second step of N-linked oligosaccharide-mediated protein folding. 25131991 11 36 located detected 1717:1724 arg1 cortex 1742:1747 the cerebral cortex 1729:1747 the cerebral cortex 1729:1747 However, a higher expression of GIIα protein was detected in the cerebral cortex, reflecting its continuous requirement in correct folding of cell surface proteins. 25131991 11 36 located detected 1717:1724 arg2 expression 1686:1695 a higher expression 1677:1695 a higher expression of GIIα protein 1677:1711 However, a higher expression of GIIα protein was detected in the cerebral cortex, reflecting its continuous requirement in correct folding of cell surface proteins. 25131991 2 37 theme catalytic 292:300 arg1 subunit 307:313 The catalytic GIIα subunit 288:313 The catalytic GIIα subunit 288:313 The catalytic GIIα subunit, with the help of mannose 6-phosphate receptor homology domain of GIIβ, sequentially hydrolyzes two α1-3-linked glucose residues in the second step of N-linked oligosaccharide-mediated protein folding. 25131991 7 38 theme widespread 1122:1131 arg1 use 1133:1135 the widespread use 1118:1135 the widespread use of GIIα inhibitory drugs and the role of GIIα in brain function 1118:1199 Despite the widespread use of GIIα inhibitory drugs and the role of GIIα in brain function, little is known about its expression in brain and other tissues. 25131991 2 39 theme mannose 333:339 arg1 receptor 353:360 mannose 6-phosphate receptor 333:360 mannose 6-phosphate receptor homology domain of GIIβ 333:384 The catalytic GIIα subunit, with the help of mannose 6-phosphate receptor homology domain of GIIβ, sequentially hydrolyzes two α1-3-linked glucose residues in the second step of N-linked oligosaccharide-mediated protein folding. 25131991 4 40 theme protein 687:693 arg1 stability 695:703 protein stability 687:703 protein stability 687:703 N-glycosylation and correct protein folding are crucial for protein stability and trafficking and cell surface expression of several proteins in the brain. 25131991 5 41 from abnormalities 822:834 arg1 migration 848:856 neuronal migration 839:856 neuronal migration 839:856 Alterations in N-glycosylation lead to abnormalities in neuronal migration and mental retardation, various neurodegenerative diseases, and invasion of malignant gliomas. 25131991 5 41 from abnormalities 822:834 arg1 retardation 869:879 mental retardation 862:879 mental retardation 862:879 Alterations in N-glycosylation lead to abnormalities in neuronal migration and mental retardation, various neurodegenerative diseases, and invasion of malignant gliomas. 25131991 9 42 theme GIIα 1498:1501 arg1 protein 1503:1509 the GIIα protein 1494:1509 the GIIα protein 1494:1509 By using this antibody, we showed that the GIIα protein is highly expressed in testis, kidney, and lung, with the lowest amount in heart. 25131991 2 43 theme GIIβ 381:384 arg1 domain 371:376 mannose 6-phosphate receptor homology domain 333:376 mannose 6-phosphate receptor homology domain of GIIβ 333:384 The catalytic GIIα subunit, with the help of mannose 6-phosphate receptor homology domain of GIIβ, sequentially hydrolyzes two α1-3-linked glucose residues in the second step of N-linked oligosaccharide-mediated protein folding. 25131991 2 43 theme GIIβ 381:384 arg1 GIIβ 381:384 GIIβ 381:384 GIIβ 381:384 The catalytic GIIα subunit, with the help of mannose 6-phosphate receptor homology domain of GIIβ, sequentially hydrolyzes two α1-3-linked glucose residues in the second step of N-linked oligosaccharide-mediated protein folding. 25131991 4 44 theme proteins 760:767 arg1 expression 738:747 cell surface expression 725:747 cell surface expression 725:747 N-glycosylation and correct protein folding are crucial for protein stability and trafficking and cell surface expression of several proteins in the brain. 25131991 4 44 theme proteins 760:767 arg1 trafficking 709:719 trafficking 709:719 trafficking 709:719 N-glycosylation and correct protein folding are crucial for protein stability and trafficking and cell surface expression of several proteins in the brain. 25131991 4 44 theme proteins 760:767 arg1 stability 695:703 protein stability 687:703 protein stability 687:703 N-glycosylation and correct protein folding are crucial for protein stability and trafficking and cell surface expression of several proteins in the brain. 25131991 11 45 theme correct 1791:1797 arg1 folding 1799:1805 correct folding 1791:1805 correct folding of cell surface proteins 1791:1830 However, a higher expression of GIIα protein was detected in the cerebral cortex, reflecting its continuous requirement in correct folding of cell surface proteins. 25131991 0 46 theme α-glucosidase 27:39 arg1 α-subunit 14:22 α-subunit 14:22 α-subunit of α-glucosidase II 14:42 Expression of α-subunit of α-glucosidase II in adult mouse brain regions and selected organs. 25131991 6 47 theme cell 991:994 arg1 proliferation 996:1008 cell proliferation 991:1008 cell proliferation 991:1008 Inhibitors of GII are used to inhibit cell proliferation and migration in a variety of different pathologies, such as viral infection, cancer, and diabetes. 25131991 0 48 theme mouse 53:57 arg1 regions 65:71 adult mouse brain regions 47:71 adult mouse brain regions 47:71 Expression of α-subunit of α-glucosidase II in adult mouse brain regions and selected organs. 25131991 8 49 theme chicken 1315:1321 arg1 antibody 1323:1330 a highly specific chicken antibody 1297:1330 a highly specific chicken antibody to the GIIα subunit 1297:1350 Here, we report generation of a highly specific chicken antibody to the GIIα subunit and its characterization by Western blotting and immunoprecipitation using cerebral cortical extracts. 25131991 10 50 theme GIIα 1593:1596 arg1 levels 1610:1615 GIIα polypeptide levels 1593:1615 GIIα polypeptide levels in whole brain 1593:1630 GIIα polypeptide levels in whole brain were comparable to those in spleen. 25131991 10 51 from levels 1610:1615 arg1 brain 1626:1630 whole brain 1620:1630 whole brain 1620:1630 GIIα polypeptide levels in whole brain were comparable to those in spleen. 25131991 3 52 theme HDEL-containing 597:611 arg1 subunit 618:624 the HDEL-containing GIIβ subunit 593:624 the HDEL-containing GIIβ subunit 593:624 The soluble GIIα subunit is retained in the ER through its interaction with the HDEL-containing GIIβ subunit. 25131991 4 53 theme surface 730:736 arg1 expression 738:747 cell surface expression 725:747 cell surface expression 725:747 N-glycosylation and correct protein folding are crucial for protein stability and trafficking and cell surface expression of several proteins in the brain. 25131991 1 54 theme enzyme 176:181 arg1 resident 120:127 resident 120:127 resident 120:127 α-Glucosidase II (GII), a resident of endoplasmic reticulum (ER) and an important enzyme in the folding of nascent glycoproteins, is heterodimeric, consisting of α (GIIα) and β (GIIβ) subunits. 25131991 1 54 theme enzyme 176:181 arg1 α-Glucosidase 94:106 α-Glucosidase II 94:109 α-Glucosidase II (GII) 94:115 α-Glucosidase II (GII), a resident of endoplasmic reticulum (ER) and an important enzyme in the folding of nascent glycoproteins, is heterodimeric, consisting of α (GIIα) and β (GIIβ) subunits. 25131991 8 55 theme GIIα 1339:1342 arg1 subunit 1344:1350 the GIIα subunit 1335:1350 the GIIα subunit 1335:1350 Here, we report generation of a highly specific chicken antibody to the GIIα subunit and its characterization by Western blotting and immunoprecipitation using cerebral cortical extracts. 25131991 10 56 theme whole 1620:1624 arg1 brain 1626:1630 whole brain 1620:1630 whole brain 1620:1630 GIIα polypeptide levels in whole brain were comparable to those in spleen. 25131991 5 57 from diseases 908:915 arg1 migration 848:856 neuronal migration 839:856 neuronal migration 839:856 Alterations in N-glycosylation lead to abnormalities in neuronal migration and mental retardation, various neurodegenerative diseases, and invasion of malignant gliomas. 25131991 5 57 from diseases 908:915 arg1 retardation 869:879 mental retardation 862:879 mental retardation 862:879 Alterations in N-glycosylation lead to abnormalities in neuronal migration and mental retardation, various neurodegenerative diseases, and invasion of malignant gliomas. 25131991 7 58 theme brain 1186:1190 arg1 function 1192:1199 brain function 1186:1199 brain function 1186:1199 Despite the widespread use of GIIα inhibitory drugs and the role of GIIα in brain function, little is known about its expression in brain and other tissues. 25131991 11 59 theme cerebral 1733:1740 arg1 cortex 1742:1747 the cerebral cortex 1729:1747 the cerebral cortex 1729:1747 However, a higher expression of GIIα protein was detected in the cerebral cortex, reflecting its continuous requirement in correct folding of cell surface proteins. 25131991 2 60 with subunit 307:313 arg1 the 321:323 the 321:323 the 321:323 The catalytic GIIα subunit, with the help of mannose 6-phosphate receptor homology domain of GIIβ, sequentially hydrolyzes two α1-3-linked glucose residues in the second step of N-linked oligosaccharide-mediated protein folding. 25131991 6 61 theme different 1040:1048 arg1 cancer 1088:1093 cancer 1088:1093 cancer 1088:1093 Inhibitors of GII are used to inhibit cell proliferation and migration in a variety of different pathologies, such as viral infection, cancer, and diabetes. 25131991 6 61 theme different 1040:1048 arg1 diabetes 1100:1107 diabetes 1100:1107 diabetes 1100:1107 Inhibitors of GII are used to inhibit cell proliferation and migration in a variety of different pathologies, such as viral infection, cancer, and diabetes. 25131991 6 61 theme different 1040:1048 arg1 infection 1077:1085 viral infection 1071:1085 viral infection 1071:1085 Inhibitors of GII are used to inhibit cell proliferation and migration in a variety of different pathologies, such as viral infection, cancer, and diabetes. 25131991 6 61 theme different 1040:1048 arg1 pathologies 1050:1060 different pathologies 1040:1060 different pathologies 1040:1060 Inhibitors of GII are used to inhibit cell proliferation and migration in a variety of different pathologies, such as viral infection, cancer, and diabetes. 25131991 1 62 theme glycoproteins 209:221 arg1 folding 190:196 the folding 186:196 the folding of nascent glycoproteins 186:221 α-Glucosidase II (GII), a resident of endoplasmic reticulum (ER) and an important enzyme in the folding of nascent glycoproteins, is heterodimeric, consisting of α (GIIα) and β (GIIβ) subunits. 25131991 1 63 theme endoplasmic 132:142 arg1 ER 155:156 ER 155:156 ER 155:156 α-Glucosidase II (GII), a resident of endoplasmic reticulum (ER) and an important enzyme in the folding of nascent glycoproteins, is heterodimeric, consisting of α (GIIα) and β (GIIβ) subunits. 25131991 1 63 theme endoplasmic 132:142 arg1 reticulum 144:152 endoplasmic reticulum 132:152 endoplasmic reticulum (ER) 132:157 α-Glucosidase II (GII), a resident of endoplasmic reticulum (ER) and an important enzyme in the folding of nascent glycoproteins, is heterodimeric, consisting of α (GIIα) and β (GIIβ) subunits. 25131991 7 64 from function 1192:1199 arg1 use 1133:1135 the widespread use 1118:1135 the widespread use of GIIα inhibitory drugs and the role of GIIα in brain function 1118:1199 Despite the widespread use of GIIα inhibitory drugs and the role of GIIα in brain function, little is known about its expression in brain and other tissues. 25131991 11 65 theme higher 1679:1684 arg1 expression 1686:1695 a higher expression 1677:1695 a higher expression of GIIα protein 1677:1711 However, a higher expression of GIIα protein was detected in the cerebral cortex, reflecting its continuous requirement in correct folding of cell surface proteins. 25131991 8 66 theme specific 1306:1313 arg1 antibody 1323:1330 a highly specific chicken antibody 1297:1330 a highly specific chicken antibody to the GIIα subunit 1297:1350 Here, we report generation of a highly specific chicken antibody to the GIIα subunit and its characterization by Western blotting and immunoprecipitation using cerebral cortical extracts. 25131991 7 67 from use 1133:1135 arg1 function 1192:1199 brain function 1186:1199 brain function 1186:1199 Despite the widespread use of GIIα inhibitory drugs and the role of GIIα in brain function, little is known about its expression in brain and other tissues. 25131991 3 68 theme soluble 521:527 arg1 subunit 534:540 The soluble GIIα subunit 517:540 The soluble GIIα subunit 517:540 The soluble GIIα subunit is retained in the ER through its interaction with the HDEL-containing GIIβ subunit. 25131991 11 69 theme protein 1705:1711 arg1 expression 1686:1695 a higher expression 1677:1695 a higher expression of GIIα protein 1677:1711 However, a higher expression of GIIα protein was detected in the cerebral cortex, reflecting its continuous requirement in correct folding of cell surface proteins. 25131991 11 70 theme surface 1815:1821 arg1 proteins 1823:1830 cell surface proteins 1810:1830 cell surface proteins 1810:1830 However, a higher expression of GIIα protein was detected in the cerebral cortex, reflecting its continuous requirement in correct folding of cell surface proteins. 25131991 5 71 theme mental 862:867 arg1 retardation 869:879 mental retardation 862:879 mental retardation 862:879 Alterations in N-glycosylation lead to abnormalities in neuronal migration and mental retardation, various neurodegenerative diseases, and invasion of malignant gliomas. 25131991 8 72 theme cerebral 1427:1434 arg1 extracts 1445:1452 cerebral cortical extracts 1427:1452 cerebral cortical extracts 1427:1452 Here, we report generation of a highly specific chicken antibody to the GIIα subunit and its characterization by Western blotting and immunoprecipitation using cerebral cortical extracts. 25131991 2 73 theme protein 500:506 arg1 folding 508:514 N-linked oligosaccharide-mediated protein folding 466:514 N-linked oligosaccharide-mediated protein folding 466:514 The catalytic GIIα subunit, with the help of mannose 6-phosphate receptor homology domain of GIIβ, sequentially hydrolyzes two α1-3-linked glucose residues in the second step of N-linked oligosaccharide-mediated protein folding. 25131991 8 74 theme Western 1380:1386 arg1 blotting 1388:1395 Western blotting 1380:1395 Western blotting 1380:1395 Here, we report generation of a highly specific chicken antibody to the GIIα subunit and its characterization by Western blotting and immunoprecipitation using cerebral cortical extracts. 25131991 1 75 from enzyme 176:181 arg1 folding 190:196 the folding 186:196 the folding of nascent glycoproteins 186:221 α-Glucosidase II (GII), a resident of endoplasmic reticulum (ER) and an important enzyme in the folding of nascent glycoproteins, is heterodimeric, consisting of α (GIIα) and β (GIIβ) subunits. 25131991 2 76 theme N-linked 466:473 arg1 folding 508:514 N-linked oligosaccharide-mediated protein folding 466:514 N-linked oligosaccharide-mediated protein folding 466:514 The catalytic GIIα subunit, with the help of mannose 6-phosphate receptor homology domain of GIIβ, sequentially hydrolyzes two α1-3-linked glucose residues in the second step of N-linked oligosaccharide-mediated protein folding. 25131991 4 77 theme protein 655:661 arg1 folding 663:669 correct protein folding 647:669 correct protein folding 647:669 N-glycosylation and correct protein folding are crucial for protein stability and trafficking and cell surface expression of several proteins in the brain. 25131991 0 78 theme brain 59:63 arg1 regions 65:71 adult mouse brain regions 47:71 adult mouse brain regions 47:71 Expression of α-subunit of α-glucosidase II in adult mouse brain regions and selected organs. 25131991 4 79 from expression 738:747 arg1 brain 776:780 the brain 772:780 the brain 772:780 N-glycosylation and correct protein folding are crucial for protein stability and trafficking and cell surface expression of several proteins in the brain. 25131991 11 80 from requirement 1776:1786 arg1 folding 1799:1805 correct folding 1791:1805 correct folding of cell surface proteins 1791:1830 However, a higher expression of GIIα protein was detected in the cerebral cortex, reflecting its continuous requirement in correct folding of cell surface proteins. 25131991 7 81 theme inhibitory 1145:1154 arg1 drugs 1156:1160 GIIα inhibitory drugs 1140:1160 GIIα inhibitory drugs 1140:1160 Despite the widespread use of GIIα inhibitory drugs and the role of GIIα in brain function, little is known about its expression in brain and other tissues. 25131991 7 82 theme drugs 1156:1160 arg1 use 1133:1135 the widespread use 1118:1135 the widespread use of GIIα inhibitory drugs and the role of GIIα in brain function 1118:1199 Despite the widespread use of GIIα inhibitory drugs and the role of GIIα in brain function, little is known about its expression in brain and other tissues. 25131991 1 83 from reticulum 144:152 arg1 folding 190:196 the folding 186:196 the folding of nascent glycoproteins 186:221 α-Glucosidase II (GII), a resident of endoplasmic reticulum (ER) and an important enzyme in the folding of nascent glycoproteins, is heterodimeric, consisting of α (GIIα) and β (GIIβ) subunits. 25131991 6 84 theme GII 967:969 arg1 Inhibitors 953:962 Inhibitors 953:962 Inhibitors of GII 953:969 Inhibitors of GII are used to inhibit cell proliferation and migration in a variety of different pathologies, such as viral infection, cancer, and diabetes. 25131991 8 85 theme cortical 1436:1443 arg1 extracts 1445:1452 cerebral cortical extracts 1427:1452 cerebral cortical extracts 1427:1452 Here, we report generation of a highly specific chicken antibody to the GIIα subunit and its characterization by Western blotting and immunoprecipitation using cerebral cortical extracts. 25131991 7 86 theme GIIα 1140:1143 arg1 drugs 1156:1160 GIIα inhibitory drugs 1140:1160 GIIα inhibitory drugs 1140:1160 Despite the widespread use of GIIα inhibitory drugs and the role of GIIα in brain function, little is known about its expression in brain and other tissues. 25131991 4 87 theme cell 725:728 arg1 expression 738:747 cell surface expression 725:747 cell surface expression 725:747 N-glycosylation and correct protein folding are crucial for protein stability and trafficking and cell surface expression of several proteins in the brain. 25131991 4 88 from trafficking 709:719 arg1 brain 776:780 the brain 772:780 the brain 772:780 N-glycosylation and correct protein folding are crucial for protein stability and trafficking and cell surface expression of several proteins in the brain. 25131991 4 89 from stability 695:703 arg1 brain 776:780 the brain 772:780 the brain 772:780 N-glycosylation and correct protein folding are crucial for protein stability and trafficking and cell surface expression of several proteins in the brain. 25131991 5 90 theme malignant 934:942 arg1 gliomas 944:950 malignant gliomas 934:950 malignant gliomas 934:950 Alterations in N-glycosylation lead to abnormalities in neuronal migration and mental retardation, various neurodegenerative diseases, and invasion of malignant gliomas. 25131991 2 91 theme α1-3-linked 415:425 arg1 residues 435:442 two α1-3-linked glucose residues 411:442 two α1-3-linked glucose residues 411:442 The catalytic GIIα subunit, with the help of mannose 6-phosphate receptor homology domain of GIIβ, sequentially hydrolyzes two α1-3-linked glucose residues in the second step of N-linked oligosaccharide-mediated protein folding. 25131991 2 92 theme GIIα 302:305 arg1 subunit 307:313 The catalytic GIIα subunit 288:313 The catalytic GIIα subunit 288:313 The catalytic GIIα subunit, with the help of mannose 6-phosphate receptor homology domain of GIIβ, sequentially hydrolyzes two α1-3-linked glucose residues in the second step of N-linked oligosaccharide-mediated protein folding. 25131991 5 93 theme neurodegenerative 890:906 arg1 diseases 908:915 various neurodegenerative diseases 882:915 various neurodegenerative diseases 882:915 Alterations in N-glycosylation lead to abnormalities in neuronal migration and mental retardation, various neurodegenerative diseases, and invasion of malignant gliomas. 25131991 2 94 theme 6-phosphate 341:351 arg1 receptor 353:360 mannose 6-phosphate receptor 333:360 mannose 6-phosphate receptor homology domain of GIIβ 333:384 The catalytic GIIα subunit, with the help of mannose 6-phosphate receptor homology domain of GIIβ, sequentially hydrolyzes two α1-3-linked glucose residues in the second step of N-linked oligosaccharide-mediated protein folding. 25131991 11 95 theme continuous 1765:1774 arg1 requirement 1776:1786 its continuous requirement 1761:1786 its continuous requirement in correct folding of cell surface proteins 1761:1830 However, a higher expression of GIIα protein was detected in the cerebral cortex, reflecting its continuous requirement in correct folding of cell surface proteins. 25131991 1 96 gly glycoproteins 209:221 arg1 glycoproteins 209:221 nascent glycoproteins 201:221 nascent glycoproteins 201:221 α-Glucosidase II (GII), a resident of endoplasmic reticulum (ER) and an important enzyme in the folding of nascent glycoproteins, is heterodimeric, consisting of α (GIIα) and β (GIIβ) subunits. 25131991 11 97 theme cell 1810:1813 arg1 proteins 1823:1830 cell surface proteins 1810:1830 cell surface proteins 1810:1830 However, a higher expression of GIIα protein was detected in the cerebral cortex, reflecting its continuous requirement in correct folding of cell surface proteins. 25131991 4 98 theme several 752:758 arg1 proteins 760:767 several proteins 752:767 several proteins 752:767 N-glycosylation and correct protein folding are crucial for protein stability and trafficking and cell surface expression of several proteins in the brain. 25131991 0 99 theme adult 47:51 arg1 regions 65:71 adult mouse brain regions 47:71 adult mouse brain regions 47:71 Expression of α-subunit of α-glucosidase II in adult mouse brain regions and selected organs. 25131991 2 100 theme homology 362:369 arg1 domain 371:376 mannose 6-phosphate receptor homology domain 333:376 mannose 6-phosphate receptor homology domain of GIIβ 333:384 The catalytic GIIα subunit, with the help of mannose 6-phosphate receptor homology domain of GIIβ, sequentially hydrolyzes two α1-3-linked glucose residues in the second step of N-linked oligosaccharide-mediated protein folding. 25131991 2 100 theme homology 362:369 arg1 GIIβ 381:384 GIIβ 381:384 GIIβ 381:384 The catalytic GIIα subunit, with the help of mannose 6-phosphate receptor homology domain of GIIβ, sequentially hydrolyzes two α1-3-linked glucose residues in the second step of N-linked oligosaccharide-mediated protein folding. 25131991 2 101 dep the 321:323 arg1 help 325:328 help 325:328 help 325:328 The catalytic GIIα subunit, with the help of mannose 6-phosphate receptor homology domain of GIIβ, sequentially hydrolyzes two α1-3-linked glucose residues in the second step of N-linked oligosaccharide-mediated protein folding. 25131991 7 102 from expression 1228:1237 arg1 brain 1242:1246 brain 1242:1246 brain 1242:1246 Despite the widespread use of GIIα inhibitory drugs and the role of GIIα in brain function, little is known about its expression in brain and other tissues. 25131991 7 102 from expression 1228:1237 arg1 tissues 1258:1264 other tissues 1252:1264 other tissues 1252:1264 Despite the widespread use of GIIα inhibitory drugs and the role of GIIα in brain function, little is known about its expression in brain and other tissues. 25131991 6 103 theme viral 1071:1075 arg1 infection 1077:1085 viral infection 1071:1085 viral infection 1071:1085 Inhibitors of GII are used to inhibit cell proliferation and migration in a variety of different pathologies, such as viral infection, cancer, and diabetes. 25131991 8 104 theme antibody 1323:1330 arg1 characterization 1360:1375 its characterization 1356:1375 its characterization by Western blotting and immunoprecipitation using cerebral cortical extracts 1356:1452 Here, we report generation of a highly specific chicken antibody to the GIIα subunit and its characterization by Western blotting and immunoprecipitation using cerebral cortical extracts. 25131991 8 104 theme antibody 1323:1330 arg1 generation 1283:1292 generation 1283:1292 generation of a highly specific chicken antibody to the GIIα subunit 1283:1350 Here, we report generation of a highly specific chicken antibody to the GIIα subunit and its characterization by Western blotting and immunoprecipitation using cerebral cortical extracts. 24498414 4 0 theme α1,2 891:894 arg1 partner 868:874 their binding partner 854:874 their binding partner 854:874 In this study, we determined the crystal structure of ERGIC-53-CRD in complex with their binding partner, MCFD2 and the α1,2 mannotriose which corresponds to the trisaccharide of the D1 arm of high-mannose-type glycans. 24498414 4 0 theme α1,2 891:894 arg1 mannotriose 896:906 the α1,2 mannotriose 887:906 the α1,2 mannotriose 887:906 In this study, we determined the crystal structure of ERGIC-53-CRD in complex with their binding partner, MCFD2 and the α1,2 mannotriose which corresponds to the trisaccharide of the D1 arm of high-mannose-type glycans. 24498414 6 1 contain has 1154:1156 arg2 pocket 1184:1189 a shallower sugar-binding pocket 1158:1189 a shallower sugar-binding pocket than VIP36 1158:1200 ERGIC-53 has a shallower sugar-binding pocket than VIP36 because of the single amino acid substitution, Asp-to-Gly. 24498414 6 1 contain has 1154:1156 arg1 ERGIC-53 1145:1152 ERGIC-53 1145:1152 ERGIC-53 1145:1152 ERGIC-53 has a shallower sugar-binding pocket than VIP36 because of the single amino acid substitution, Asp-to-Gly. 24498414 3 2 theme terminal 731:738 arg1 residue 748:754 the non-reducing terminal glucose residue 714:754 the non-reducing terminal glucose residue at the D1 arm 714:768 VIP36 specifically interacts with the α1,2-linked D1 mannosyl arm without terminal glucosylation, while ERGIC-53 shows a broader specificity and lower binding affinity to the high-mannose-type oligosaccharides, irrespective of the presence or absence of the non-reducing terminal glucose residue at the D1 arm. 24498414 3 3 theme terminal 534:541 arg1 glucosylation 543:555 terminal glucosylation 534:555 terminal glucosylation 534:555 VIP36 specifically interacts with the α1,2-linked D1 mannosyl arm without terminal glucosylation, while ERGIC-53 shows a broader specificity and lower binding affinity to the high-mannose-type oligosaccharides, irrespective of the presence or absence of the non-reducing terminal glucose residue at the D1 arm. 24498414 1 4 theme N-linked 246:253 arg1 glycoproteins 255:267 trafficking certain N-linked glycoproteins 226:267 trafficking certain N-linked glycoproteins in the secretory pathway in animal cells 226:308 ERGIC-53 and VIP36 are categorized as leguminous type (L-type) lectins, and they function as cargo receptors for trafficking certain N-linked glycoproteins in the secretory pathway in animal cells. 24498414 9 5 theme ERGIC-53/MCFD2 1653:1666 arg1 complex 1683:1689 the ERGIC-53/MCFD2 cargo receptor complex 1649:1689 the ERGIC-53/MCFD2 cargo receptor complex 1649:1689 Our findings thus provide a structural basis for the broad sugar-binding specificity of the ERGIC-53/MCFD2 cargo receptor complex. 24498414 9 6 theme receptor 1674:1681 arg1 complex 1683:1689 the ERGIC-53/MCFD2 cargo receptor complex 1649:1689 the ERGIC-53/MCFD2 cargo receptor complex 1649:1689 Our findings thus provide a structural basis for the broad sugar-binding specificity of the ERGIC-53/MCFD2 cargo receptor complex. 24498414 2 7 from similarities 333:344 arg1 CRDs 389:392 CRDs 389:392 CRDs 389:392 They share structural similarities in their carbohydrate recognition domains (CRDs) but exhibit distinct sugar-binding specificities and affinities. 24498414 2 7 from similarities 333:344 arg1 domains 380:386 carbohydrate recognition domains 355:386 their carbohydrate recognition domains (CRDs) 349:393 They share structural similarities in their carbohydrate recognition domains (CRDs) but exhibit distinct sugar-binding specificities and affinities. 24498414 6 8 theme sugar-binding 1170:1182 arg1 pocket 1184:1189 a shallower sugar-binding pocket 1158:1189 a shallower sugar-binding pocket than VIP36 1158:1200 ERGIC-53 has a shallower sugar-binding pocket than VIP36 because of the single amino acid substitution, Asp-to-Gly. 24498414 3 9 theme lower 605:609 arg1 affinity 619:626 lower binding affinity 605:626 lower binding affinity 605:626 VIP36 specifically interacts with the α1,2-linked D1 mannosyl arm without terminal glucosylation, while ERGIC-53 shows a broader specificity and lower binding affinity to the high-mannose-type oligosaccharides, irrespective of the presence or absence of the non-reducing terminal glucose residue at the D1 arm. 24498414 4 10 theme arm 957:959 arg1 trisaccharide 933:945 the trisaccharide 929:945 the trisaccharide of the D1 arm of high-mannose-type glycans 929:988 In this study, we determined the crystal structure of ERGIC-53-CRD in complex with their binding partner, MCFD2 and the α1,2 mannotriose which corresponds to the trisaccharide of the D1 arm of high-mannose-type glycans. 24498414 9 11 theme sugar-binding 1620:1632 arg1 specificity 1634:1644 the broad sugar-binding specificity 1610:1644 the broad sugar-binding specificity of the ERGIC-53/MCFD2 cargo receptor complex 1610:1689 Our findings thus provide a structural basis for the broad sugar-binding specificity of the ERGIC-53/MCFD2 cargo receptor complex. 24498414 3 12 link α1,2-linked 498:508 arg1 arm 522:524 the α1,2-linked D1 mannosyl arm 494:524 the α1,2-linked D1 mannosyl arm 494:524 VIP36 specifically interacts with the α1,2-linked D1 mannosyl arm without terminal glucosylation, while ERGIC-53 shows a broader specificity and lower binding affinity to the high-mannose-type oligosaccharides, irrespective of the presence or absence of the non-reducing terminal glucose residue at the D1 arm. 24498414 6 13 theme amino 1224:1228 arg1 substitution 1235:1246 the single amino acid substitution 1213:1246 the single amino acid substitution 1213:1246 ERGIC-53 has a shallower sugar-binding pocket than VIP36 because of the single amino acid substitution, Asp-to-Gly. 24498414 6 13 theme amino 1224:1228 arg1 Asp-to-Gly 1249:1258 Asp-to-Gly 1249:1258 Asp-to-Gly 1249:1258 ERGIC-53 has a shallower sugar-binding pocket than VIP36 because of the single amino acid substitution, Asp-to-Gly. 24498414 3 14 theme irrespective 671:682 arg1 oligosaccharides 653:668 the high-mannose-type oligosaccharides 631:668 the high-mannose-type oligosaccharides 631:668 VIP36 specifically interacts with the α1,2-linked D1 mannosyl arm without terminal glucosylation, while ERGIC-53 shows a broader specificity and lower binding affinity to the high-mannose-type oligosaccharides, irrespective of the presence or absence of the non-reducing terminal glucose residue at the D1 arm. 24498414 8 15 theme sugar 1469:1473 arg1 pocket 1483:1488 the sugar binding pocket 1465:1488 the sugar binding pocket 1465:1488 In the other interaction mode, the 3-OH group of the terminal mannose was situated outward with respect to the sugar binding pocket, also enabling the Glcα1-3 linkage formation without steric hindrance. 24498414 0 16 theme homologous 66:75 arg1 receptors 83:91 the homologous cargo receptors 62:91 the homologous cargo receptors ERGIC-53 and VIP36 62:110 Structural basis for disparate sugar-binding specificities in the homologous cargo receptors ERGIC-53 and VIP36. 24498414 0 16 theme homologous 66:75 arg1 VIP36 106:110 VIP36 106:110 VIP36 106:110 Structural basis for disparate sugar-binding specificities in the homologous cargo receptors ERGIC-53 and VIP36. 24498414 0 16 theme homologous 66:75 arg1 ERGIC-53 93:100 ERGIC-53 93:100 ERGIC-53 93:100 Structural basis for disparate sugar-binding specificities in the homologous cargo receptors ERGIC-53 and VIP36. 24498414 3 17 dep specificity 589:599 arg1 a 579:579 a 579:579 a 579:579 VIP36 specifically interacts with the α1,2-linked D1 mannosyl arm without terminal glucosylation, while ERGIC-53 shows a broader specificity and lower binding affinity to the high-mannose-type oligosaccharides, irrespective of the presence or absence of the non-reducing terminal glucose residue at the D1 arm. 24498414 4 18 theme high-mannose-type 964:980 arg1 glycans 982:988 high-mannose-type glycans 964:988 high-mannose-type glycans 964:988 In this study, we determined the crystal structure of ERGIC-53-CRD in complex with their binding partner, MCFD2 and the α1,2 mannotriose which corresponds to the trisaccharide of the D1 arm of high-mannose-type glycans. 24498414 4 19 theme crystal 804:810 arg1 structure 812:820 the crystal structure 800:820 the crystal structure of ERGIC-53-CRD in complex with their binding partner, MCFD2 and the α1,2 mannotriose which corresponds to the trisaccharide of the D1 arm of high-mannose-type glycans 800:988 In this study, we determined the crystal structure of ERGIC-53-CRD in complex with their binding partner, MCFD2 and the α1,2 mannotriose which corresponds to the trisaccharide of the D1 arm of high-mannose-type glycans. 24498414 8 20 theme linkage 1517:1523 arg1 formation 1525:1533 the Glcα1-3 linkage formation 1505:1533 the Glcα1-3 linkage formation 1505:1533 In the other interaction mode, the 3-OH group of the terminal mannose was situated outward with respect to the sugar binding pocket, also enabling the Glcα1-3 linkage formation without steric hindrance. 24498414 8 21 theme interaction 1371:1381 arg1 mode 1383:1386 the other interaction mode 1361:1386 the other interaction mode 1361:1386 In the other interaction mode, the 3-OH group of the terminal mannose was situated outward with respect to the sugar binding pocket, also enabling the Glcα1-3 linkage formation without steric hindrance. 24498414 0 22 theme Structural 0:9 arg1 basis 11:15 Structural basis 0:15 Structural basis for disparate sugar-binding specificities in the homologous cargo receptors ERGIC-53 and VIP36. 0:111 Structural basis for disparate sugar-binding specificities in the homologous cargo receptors ERGIC-53 and VIP36. 24498414 0 23 dep receptors 83:91 arg1 receptors 83:91 the homologous cargo receptors 62:91 the homologous cargo receptors ERGIC-53 and VIP36 62:110 Structural basis for disparate sugar-binding specificities in the homologous cargo receptors ERGIC-53 and VIP36. 24498414 0 23 dep receptors 83:91 arg1 VIP36 106:110 VIP36 106:110 VIP36 106:110 Structural basis for disparate sugar-binding specificities in the homologous cargo receptors ERGIC-53 and VIP36. 24498414 0 23 dep receptors 83:91 arg1 ERGIC-53 93:100 ERGIC-53 93:100 ERGIC-53 93:100 Structural basis for disparate sugar-binding specificities in the homologous cargo receptors ERGIC-53 and VIP36. 24498414 7 24 theme arm 1342:1344 arg1 glucose 1324:1330 the non-reducing terminal glucose 1298:1330 the non-reducing terminal glucose of the D1 arm in its CRD 1298:1355 This enables ERGIC-53 to accommodate the non-reducing terminal glucose of the D1 arm in its CRD. 24498414 5 25 from that 1109:1112 arg1 distinct 1095:1102 distinct 1095:1102 distinct 1095:1102 ERGIC-53 can interact with the D1 trimannosyl arm in two alternative modes, one of which is similar but distinct from that previously observed for VIP36. 24498414 8 26 theme 3-OH 1393:1396 arg1 group 1398:1402 the 3-OH group 1389:1402 the 3-OH group of the terminal mannose 1389:1426 In the other interaction mode, the 3-OH group of the terminal mannose was situated outward with respect to the sugar binding pocket, also enabling the Glcα1-3 linkage formation without steric hindrance. 24498414 8 26 theme 3-OH 1393:1396 arg1 mannose 1420:1426 the terminal mannose 1407:1426 the terminal mannose 1407:1426 In the other interaction mode, the 3-OH group of the terminal mannose was situated outward with respect to the sugar binding pocket, also enabling the Glcα1-3 linkage formation without steric hindrance. 24498414 8 26 theme 3-OH 1393:1396 arg1 outward 1441:1447 outward 1441:1447 outward 1441:1447 In the other interaction mode, the 3-OH group of the terminal mannose was situated outward with respect to the sugar binding pocket, also enabling the Glcα1-3 linkage formation without steric hindrance. 24498414 2 27 theme distinct 407:414 arg1 specificities 430:442 distinct sugar-binding specificities 407:442 distinct sugar-binding specificities 407:442 They share structural similarities in their carbohydrate recognition domains (CRDs) but exhibit distinct sugar-binding specificities and affinities. 24498414 0 28 theme sugar-binding 31:43 arg1 specificities 45:57 disparate sugar-binding specificities 21:57 disparate sugar-binding specificities in the homologous cargo receptors ERGIC-53 and VIP36 21:110 Structural basis for disparate sugar-binding specificities in the homologous cargo receptors ERGIC-53 and VIP36. 24498414 1 29 theme animal 297:302 arg1 cells 304:308 animal cells 297:308 animal cells 297:308 ERGIC-53 and VIP36 are categorized as leguminous type (L-type) lectins, and they function as cargo receptors for trafficking certain N-linked glycoproteins in the secretory pathway in animal cells. 24498414 9 30 theme structural 1589:1598 arg1 basis 1600:1604 a structural basis 1587:1604 a structural basis for the broad sugar-binding specificity of the ERGIC-53/MCFD2 cargo receptor complex 1587:1689 Our findings thus provide a structural basis for the broad sugar-binding specificity of the ERGIC-53/MCFD2 cargo receptor complex. 24498414 4 31 theme binding 860:866 arg1 MCFD2 877:881 MCFD2 877:881 MCFD2 877:881 In this study, we determined the crystal structure of ERGIC-53-CRD in complex with their binding partner, MCFD2 and the α1,2 mannotriose which corresponds to the trisaccharide of the D1 arm of high-mannose-type glycans. 24498414 4 31 theme binding 860:866 arg1 partner 868:874 their binding partner 854:874 their binding partner 854:874 In this study, we determined the crystal structure of ERGIC-53-CRD in complex with their binding partner, MCFD2 and the α1,2 mannotriose which corresponds to the trisaccharide of the D1 arm of high-mannose-type glycans. 24498414 4 31 theme binding 860:866 arg1 mannotriose 896:906 the α1,2 mannotriose 887:906 the α1,2 mannotriose 887:906 In this study, we determined the crystal structure of ERGIC-53-CRD in complex with their binding partner, MCFD2 and the α1,2 mannotriose which corresponds to the trisaccharide of the D1 arm of high-mannose-type glycans. 24498414 3 32 theme mannosyl 513:520 arg1 arm 522:524 the α1,2-linked D1 mannosyl arm 494:524 the α1,2-linked D1 mannosyl arm 494:524 VIP36 specifically interacts with the α1,2-linked D1 mannosyl arm without terminal glucosylation, while ERGIC-53 shows a broader specificity and lower binding affinity to the high-mannose-type oligosaccharides, irrespective of the presence or absence of the non-reducing terminal glucose residue at the D1 arm. 24498414 5 33 theme modes 1060:1064 arg1 one 1067:1069 one 1067:1069 one 1067:1069 ERGIC-53 can interact with the D1 trimannosyl arm in two alternative modes, one of which is similar but distinct from that previously observed for VIP36. 24498414 5 33 theme modes 1060:1064 arg1 modes 1060:1064 two alternative modes 1044:1064 two alternative modes 1044:1064 ERGIC-53 can interact with the D1 trimannosyl arm in two alternative modes, one of which is similar but distinct from that previously observed for VIP36. 24498414 7 34 theme non-reducing 1302:1313 arg1 glucose 1324:1330 the non-reducing terminal glucose 1298:1330 the non-reducing terminal glucose of the D1 arm in its CRD 1298:1355 This enables ERGIC-53 to accommodate the non-reducing terminal glucose of the D1 arm in its CRD. 24498414 3 35 theme non-reducing 718:729 arg1 residue 748:754 the non-reducing terminal glucose residue 714:754 the non-reducing terminal glucose residue at the D1 arm 714:768 VIP36 specifically interacts with the α1,2-linked D1 mannosyl arm without terminal glucosylation, while ERGIC-53 shows a broader specificity and lower binding affinity to the high-mannose-type oligosaccharides, irrespective of the presence or absence of the non-reducing terminal glucose residue at the D1 arm. 24498414 8 36 theme terminal 1411:1418 arg1 mannose 1420:1426 the terminal mannose 1407:1426 the terminal mannose 1407:1426 In the other interaction mode, the 3-OH group of the terminal mannose was situated outward with respect to the sugar binding pocket, also enabling the Glcα1-3 linkage formation without steric hindrance. 24498414 2 37 theme structural 322:331 arg1 similarities 333:344 structural similarities 322:344 structural similarities in their carbohydrate recognition domains (CRDs) 322:393 They share structural similarities in their carbohydrate recognition domains (CRDs) but exhibit distinct sugar-binding specificities and affinities. 24498414 1 38 theme cargo 206:210 arg1 they 189:192 they 189:192 they 189:192 ERGIC-53 and VIP36 are categorized as leguminous type (L-type) lectins, and they function as cargo receptors for trafficking certain N-linked glycoproteins in the secretory pathway in animal cells. 24498414 1 38 theme cargo 206:210 arg1 receptors 212:220 cargo receptors 206:220 cargo receptors for trafficking certain N-linked glycoproteins in the secretory pathway in animal cells 206:308 ERGIC-53 and VIP36 are categorized as leguminous type (L-type) lectins, and they function as cargo receptors for trafficking certain N-linked glycoproteins in the secretory pathway in animal cells. 24498414 5 39 theme D1 1022:1023 arg1 arm 1037:1039 the D1 trimannosyl arm 1018:1039 the D1 trimannosyl arm 1018:1039 ERGIC-53 can interact with the D1 trimannosyl arm in two alternative modes, one of which is similar but distinct from that previously observed for VIP36. 24498414 1 40 theme leguminous 151:160 arg1 lectins 176:182 leguminous type (L-type) lectins 151:182 leguminous type (L-type) lectins 151:182 ERGIC-53 and VIP36 are categorized as leguminous type (L-type) lectins, and they function as cargo receptors for trafficking certain N-linked glycoproteins in the secretory pathway in animal cells. 24498414 1 40 theme leguminous 151:160 arg1 VIP36 126:130 VIP36 126:130 VIP36 126:130 ERGIC-53 and VIP36 are categorized as leguminous type (L-type) lectins, and they function as cargo receptors for trafficking certain N-linked glycoproteins in the secretory pathway in animal cells. 24498414 1 40 theme leguminous 151:160 arg1 ERGIC-53 113:120 ERGIC-53 113:120 ERGIC-53 113:120 ERGIC-53 and VIP36 are categorized as leguminous type (L-type) lectins, and they function as cargo receptors for trafficking certain N-linked glycoproteins in the secretory pathway in animal cells. 24498414 3 41 from absence 703:709 arg1 arm 766:768 the D1 arm 759:768 the D1 arm 759:768 VIP36 specifically interacts with the α1,2-linked D1 mannosyl arm without terminal glucosylation, while ERGIC-53 shows a broader specificity and lower binding affinity to the high-mannose-type oligosaccharides, irrespective of the presence or absence of the non-reducing terminal glucose residue at the D1 arm. 24498414 3 42 dep presence 691:698 arg1 the 687:689 the 687:689 the 687:689 VIP36 specifically interacts with the α1,2-linked D1 mannosyl arm without terminal glucosylation, while ERGIC-53 shows a broader specificity and lower binding affinity to the high-mannose-type oligosaccharides, irrespective of the presence or absence of the non-reducing terminal glucose residue at the D1 arm. 24498414 2 43 theme carbohydrate 355:366 arg1 CRDs 389:392 CRDs 389:392 CRDs 389:392 They share structural similarities in their carbohydrate recognition domains (CRDs) but exhibit distinct sugar-binding specificities and affinities. 24498414 2 43 theme carbohydrate 355:366 arg1 domains 380:386 carbohydrate recognition domains 355:386 their carbohydrate recognition domains (CRDs) 349:393 They share structural similarities in their carbohydrate recognition domains (CRDs) but exhibit distinct sugar-binding specificities and affinities. 24498414 8 44 from mode 1383:1386 arg1 group 1398:1402 the 3-OH group 1389:1402 the 3-OH group of the terminal mannose 1389:1426 In the other interaction mode, the 3-OH group of the terminal mannose was situated outward with respect to the sugar binding pocket, also enabling the Glcα1-3 linkage formation without steric hindrance. 24498414 8 44 from mode 1383:1386 arg1 mannose 1420:1426 the terminal mannose 1407:1426 the terminal mannose 1407:1426 In the other interaction mode, the 3-OH group of the terminal mannose was situated outward with respect to the sugar binding pocket, also enabling the Glcα1-3 linkage formation without steric hindrance. 24498414 8 44 from mode 1383:1386 arg1 outward 1441:1447 outward 1441:1447 outward 1441:1447 In the other interaction mode, the 3-OH group of the terminal mannose was situated outward with respect to the sugar binding pocket, also enabling the Glcα1-3 linkage formation without steric hindrance. 24498414 1 45 theme certain 238:244 arg1 glycoproteins 255:267 trafficking certain N-linked glycoproteins 226:267 trafficking certain N-linked glycoproteins in the secretory pathway in animal cells 226:308 ERGIC-53 and VIP36 are categorized as leguminous type (L-type) lectins, and they function as cargo receptors for trafficking certain N-linked glycoproteins in the secretory pathway in animal cells. 24498414 3 46 theme glucose 740:746 arg1 residue 748:754 the non-reducing terminal glucose residue 714:754 the non-reducing terminal glucose residue at the D1 arm 714:768 VIP36 specifically interacts with the α1,2-linked D1 mannosyl arm without terminal glucosylation, while ERGIC-53 shows a broader specificity and lower binding affinity to the high-mannose-type oligosaccharides, irrespective of the presence or absence of the non-reducing terminal glucose residue at the D1 arm. 24498414 9 47 theme cargo 1668:1672 arg1 complex 1683:1689 the ERGIC-53/MCFD2 cargo receptor complex 1649:1689 the ERGIC-53/MCFD2 cargo receptor complex 1649:1689 Our findings thus provide a structural basis for the broad sugar-binding specificity of the ERGIC-53/MCFD2 cargo receptor complex. 24498414 3 48 from presence 691:698 arg1 arm 766:768 the D1 arm 759:768 the D1 arm 759:768 VIP36 specifically interacts with the α1,2-linked D1 mannosyl arm without terminal glucosylation, while ERGIC-53 shows a broader specificity and lower binding affinity to the high-mannose-type oligosaccharides, irrespective of the presence or absence of the non-reducing terminal glucose residue at the D1 arm. 24498414 1 49 from pathway 286:292 arg1 cells 304:308 animal cells 297:308 animal cells 297:308 ERGIC-53 and VIP36 are categorized as leguminous type (L-type) lectins, and they function as cargo receptors for trafficking certain N-linked glycoproteins in the secretory pathway in animal cells. 24498414 1 50 link N-linked 246:253 arg1 glycoproteins 255:267 trafficking certain N-linked glycoproteins 226:267 trafficking certain N-linked glycoproteins in the secretory pathway in animal cells 226:308 ERGIC-53 and VIP36 are categorized as leguminous type (L-type) lectins, and they function as cargo receptors for trafficking certain N-linked glycoproteins in the secretory pathway in animal cells. 24498414 1 51 theme L-type 168:173 arg1 lectins 176:182 leguminous type (L-type) lectins 151:182 leguminous type (L-type) lectins 151:182 ERGIC-53 and VIP36 are categorized as leguminous type (L-type) lectins, and they function as cargo receptors for trafficking certain N-linked glycoproteins in the secretory pathway in animal cells. 24498414 1 51 theme L-type 168:173 arg1 VIP36 126:130 VIP36 126:130 VIP36 126:130 ERGIC-53 and VIP36 are categorized as leguminous type (L-type) lectins, and they function as cargo receptors for trafficking certain N-linked glycoproteins in the secretory pathway in animal cells. 24498414 1 51 theme L-type 168:173 arg1 ERGIC-53 113:120 ERGIC-53 113:120 ERGIC-53 113:120 ERGIC-53 and VIP36 are categorized as leguminous type (L-type) lectins, and they function as cargo receptors for trafficking certain N-linked glycoproteins in the secretory pathway in animal cells. 24498414 9 52 theme complex 1683:1689 arg1 specificity 1634:1644 the broad sugar-binding specificity 1610:1644 the broad sugar-binding specificity of the ERGIC-53/MCFD2 cargo receptor complex 1610:1689 Our findings thus provide a structural basis for the broad sugar-binding specificity of the ERGIC-53/MCFD2 cargo receptor complex. 24498414 3 53 theme D1 763:764 arg1 arm 766:768 the D1 arm 759:768 the D1 arm 759:768 VIP36 specifically interacts with the α1,2-linked D1 mannosyl arm without terminal glucosylation, while ERGIC-53 shows a broader specificity and lower binding affinity to the high-mannose-type oligosaccharides, irrespective of the presence or absence of the non-reducing terminal glucose residue at the D1 arm. 24498414 6 54 theme shallower 1160:1168 arg1 pocket 1184:1189 a shallower sugar-binding pocket 1158:1189 a shallower sugar-binding pocket than VIP36 1158:1200 ERGIC-53 has a shallower sugar-binding pocket than VIP36 because of the single amino acid substitution, Asp-to-Gly. 24498414 3 55 from arm 766:768 arg1 presence 691:698 presence 691:698 presence 691:698 VIP36 specifically interacts with the α1,2-linked D1 mannosyl arm without terminal glucosylation, while ERGIC-53 shows a broader specificity and lower binding affinity to the high-mannose-type oligosaccharides, irrespective of the presence or absence of the non-reducing terminal glucose residue at the D1 arm. 24498414 3 55 from arm 766:768 arg1 residue 748:754 the non-reducing terminal glucose residue 714:754 the non-reducing terminal glucose residue at the D1 arm 714:768 VIP36 specifically interacts with the α1,2-linked D1 mannosyl arm without terminal glucosylation, while ERGIC-53 shows a broader specificity and lower binding affinity to the high-mannose-type oligosaccharides, irrespective of the presence or absence of the non-reducing terminal glucose residue at the D1 arm. 24498414 3 55 from arm 766:768 arg1 absence 703:709 absence 703:709 absence 703:709 VIP36 specifically interacts with the α1,2-linked D1 mannosyl arm without terminal glucosylation, while ERGIC-53 shows a broader specificity and lower binding affinity to the high-mannose-type oligosaccharides, irrespective of the presence or absence of the non-reducing terminal glucose residue at the D1 arm. 24498414 1 56 from glycoproteins 255:267 arg1 pathway 286:292 the secretory pathway 272:292 the secretory pathway in animal cells 272:308 ERGIC-53 and VIP36 are categorized as leguminous type (L-type) lectins, and they function as cargo receptors for trafficking certain N-linked glycoproteins in the secretory pathway in animal cells. 24498414 3 57 theme broader 581:587 arg1 specificity 589:599 broader specificity 581:599 broader specificity 581:599 VIP36 specifically interacts with the α1,2-linked D1 mannosyl arm without terminal glucosylation, while ERGIC-53 shows a broader specificity and lower binding affinity to the high-mannose-type oligosaccharides, irrespective of the presence or absence of the non-reducing terminal glucose residue at the D1 arm. 24498414 4 58 theme D1 954:955 arg1 glycans 982:988 high-mannose-type glycans 964:988 high-mannose-type glycans 964:988 In this study, we determined the crystal structure of ERGIC-53-CRD in complex with their binding partner, MCFD2 and the α1,2 mannotriose which corresponds to the trisaccharide of the D1 arm of high-mannose-type glycans. 24498414 4 58 theme D1 954:955 arg1 arm 957:959 the D1 arm 950:959 the D1 arm of high-mannose-type glycans 950:988 In this study, we determined the crystal structure of ERGIC-53-CRD in complex with their binding partner, MCFD2 and the α1,2 mannotriose which corresponds to the trisaccharide of the D1 arm of high-mannose-type glycans. 24498414 3 59 theme binding 611:617 arg1 affinity 619:626 lower binding affinity 605:626 lower binding affinity 605:626 VIP36 specifically interacts with the α1,2-linked D1 mannosyl arm without terminal glucosylation, while ERGIC-53 shows a broader specificity and lower binding affinity to the high-mannose-type oligosaccharides, irrespective of the presence or absence of the non-reducing terminal glucose residue at the D1 arm. 24498414 6 60 theme acid 1230:1233 arg1 substitution 1235:1246 the single amino acid substitution 1213:1246 the single amino acid substitution 1213:1246 ERGIC-53 has a shallower sugar-binding pocket than VIP36 because of the single amino acid substitution, Asp-to-Gly. 24498414 6 60 theme acid 1230:1233 arg1 Asp-to-Gly 1249:1258 Asp-to-Gly 1249:1258 Asp-to-Gly 1249:1258 ERGIC-53 has a shallower sugar-binding pocket than VIP36 because of the single amino acid substitution, Asp-to-Gly. 24498414 8 61 theme binding 1475:1481 arg1 pocket 1483:1488 the sugar binding pocket 1465:1488 the sugar binding pocket 1465:1488 In the other interaction mode, the 3-OH group of the terminal mannose was situated outward with respect to the sugar binding pocket, also enabling the Glcα1-3 linkage formation without steric hindrance. 24498414 6 62 theme single 1217:1222 arg1 substitution 1235:1246 the single amino acid substitution 1213:1246 the single amino acid substitution 1213:1246 ERGIC-53 has a shallower sugar-binding pocket than VIP36 because of the single amino acid substitution, Asp-to-Gly. 24498414 6 62 theme single 1217:1222 arg1 Asp-to-Gly 1249:1258 Asp-to-Gly 1249:1258 Asp-to-Gly 1249:1258 ERGIC-53 has a shallower sugar-binding pocket than VIP36 because of the single amino acid substitution, Asp-to-Gly. 24498414 3 63 theme α1,2-linked 498:508 arg1 arm 522:524 the α1,2-linked D1 mannosyl arm 494:524 the α1,2-linked D1 mannosyl arm 494:524 VIP36 specifically interacts with the α1,2-linked D1 mannosyl arm without terminal glucosylation, while ERGIC-53 shows a broader specificity and lower binding affinity to the high-mannose-type oligosaccharides, irrespective of the presence or absence of the non-reducing terminal glucose residue at the D1 arm. 24498414 0 64 theme cargo 77:81 arg1 receptors 83:91 the homologous cargo receptors 62:91 the homologous cargo receptors ERGIC-53 and VIP36 62:110 Structural basis for disparate sugar-binding specificities in the homologous cargo receptors ERGIC-53 and VIP36. 24498414 0 64 theme cargo 77:81 arg1 VIP36 106:110 VIP36 106:110 VIP36 106:110 Structural basis for disparate sugar-binding specificities in the homologous cargo receptors ERGIC-53 and VIP36. 24498414 0 64 theme cargo 77:81 arg1 ERGIC-53 93:100 ERGIC-53 93:100 ERGIC-53 93:100 Structural basis for disparate sugar-binding specificities in the homologous cargo receptors ERGIC-53 and VIP36. 24498414 3 65 theme high-mannose-type 635:651 arg1 oligosaccharides 653:668 the high-mannose-type oligosaccharides 631:668 the high-mannose-type oligosaccharides 631:668 VIP36 specifically interacts with the α1,2-linked D1 mannosyl arm without terminal glucosylation, while ERGIC-53 shows a broader specificity and lower binding affinity to the high-mannose-type oligosaccharides, irrespective of the presence or absence of the non-reducing terminal glucose residue at the D1 arm. 24498414 4 66 with complex 841:847 arg1 MCFD2 877:881 MCFD2 877:881 MCFD2 877:881 In this study, we determined the crystal structure of ERGIC-53-CRD in complex with their binding partner, MCFD2 and the α1,2 mannotriose which corresponds to the trisaccharide of the D1 arm of high-mannose-type glycans. 24498414 4 66 with complex 841:847 arg1 partner 868:874 their binding partner 854:874 their binding partner 854:874 In this study, we determined the crystal structure of ERGIC-53-CRD in complex with their binding partner, MCFD2 and the α1,2 mannotriose which corresponds to the trisaccharide of the D1 arm of high-mannose-type glycans. 24498414 4 66 with complex 841:847 arg1 mannotriose 896:906 the α1,2 mannotriose 887:906 the α1,2 mannotriose 887:906 In this study, we determined the crystal structure of ERGIC-53-CRD in complex with their binding partner, MCFD2 and the α1,2 mannotriose which corresponds to the trisaccharide of the D1 arm of high-mannose-type glycans. 24498414 8 67 from outward 1441:1447 arg1 mode 1383:1386 the other interaction mode 1361:1386 the other interaction mode 1361:1386 In the other interaction mode, the 3-OH group of the terminal mannose was situated outward with respect to the sugar binding pocket, also enabling the Glcα1-3 linkage formation without steric hindrance. 24498414 4 68 from structure 812:820 arg1 complex 841:847 complex 841:847 complex with their binding partner, MCFD2 and the α1,2 mannotriose which corresponds to the trisaccharide of the D1 arm of high-mannose-type glycans 841:988 In this study, we determined the crystal structure of ERGIC-53-CRD in complex with their binding partner, MCFD2 and the α1,2 mannotriose which corresponds to the trisaccharide of the D1 arm of high-mannose-type glycans. 24498414 1 69 theme type 162:165 arg1 lectins 176:182 leguminous type (L-type) lectins 151:182 leguminous type (L-type) lectins 151:182 ERGIC-53 and VIP36 are categorized as leguminous type (L-type) lectins, and they function as cargo receptors for trafficking certain N-linked glycoproteins in the secretory pathway in animal cells. 24498414 1 69 theme type 162:165 arg1 VIP36 126:130 VIP36 126:130 VIP36 126:130 ERGIC-53 and VIP36 are categorized as leguminous type (L-type) lectins, and they function as cargo receptors for trafficking certain N-linked glycoproteins in the secretory pathway in animal cells. 24498414 1 69 theme type 162:165 arg1 ERGIC-53 113:120 ERGIC-53 113:120 ERGIC-53 113:120 ERGIC-53 and VIP36 are categorized as leguminous type (L-type) lectins, and they function as cargo receptors for trafficking certain N-linked glycoproteins in the secretory pathway in animal cells. 24498414 9 70 theme broad 1614:1618 arg1 specificity 1634:1644 the broad sugar-binding specificity 1610:1644 the broad sugar-binding specificity of the ERGIC-53/MCFD2 cargo receptor complex 1610:1689 Our findings thus provide a structural basis for the broad sugar-binding specificity of the ERGIC-53/MCFD2 cargo receptor complex. 24498414 8 71 theme Glcα1-3 1509:1515 arg1 formation 1525:1533 the Glcα1-3 linkage formation 1505:1533 the Glcα1-3 linkage formation 1505:1533 In the other interaction mode, the 3-OH group of the terminal mannose was situated outward with respect to the sugar binding pocket, also enabling the Glcα1-3 linkage formation without steric hindrance. 24498414 4 72 theme glycans 982:988 arg1 glycans 982:988 high-mannose-type glycans 964:988 high-mannose-type glycans 964:988 In this study, we determined the crystal structure of ERGIC-53-CRD in complex with their binding partner, MCFD2 and the α1,2 mannotriose which corresponds to the trisaccharide of the D1 arm of high-mannose-type glycans. 24498414 4 72 theme glycans 982:988 arg1 arm 957:959 the D1 arm 950:959 the D1 arm of high-mannose-type glycans 950:988 In this study, we determined the crystal structure of ERGIC-53-CRD in complex with their binding partner, MCFD2 and the α1,2 mannotriose which corresponds to the trisaccharide of the D1 arm of high-mannose-type glycans. 24498414 0 73 from specificities 45:57 arg1 receptors 83:91 the homologous cargo receptors 62:91 the homologous cargo receptors ERGIC-53 and VIP36 62:110 Structural basis for disparate sugar-binding specificities in the homologous cargo receptors ERGIC-53 and VIP36. 24498414 0 73 from specificities 45:57 arg1 VIP36 106:110 VIP36 106:110 VIP36 106:110 Structural basis for disparate sugar-binding specificities in the homologous cargo receptors ERGIC-53 and VIP36. 24498414 0 73 from specificities 45:57 arg1 ERGIC-53 93:100 ERGIC-53 93:100 ERGIC-53 93:100 Structural basis for disparate sugar-binding specificities in the homologous cargo receptors ERGIC-53 and VIP36. 24498414 7 74 theme D1 1339:1340 arg1 arm 1342:1344 the D1 arm 1335:1344 the D1 arm 1335:1344 This enables ERGIC-53 to accommodate the non-reducing terminal glucose of the D1 arm in its CRD. 24498414 8 75 theme steric 1543:1548 arg1 hindrance 1550:1558 steric hindrance 1543:1558 steric hindrance 1543:1558 In the other interaction mode, the 3-OH group of the terminal mannose was situated outward with respect to the sugar binding pocket, also enabling the Glcα1-3 linkage formation without steric hindrance. 24498414 8 76 theme other 1365:1369 arg1 mode 1383:1386 the other interaction mode 1361:1386 the other interaction mode 1361:1386 In the other interaction mode, the 3-OH group of the terminal mannose was situated outward with respect to the sugar binding pocket, also enabling the Glcα1-3 linkage formation without steric hindrance. 24498414 0 77 theme disparate 21:29 arg1 specificities 45:57 disparate sugar-binding specificities 21:57 disparate sugar-binding specificities in the homologous cargo receptors ERGIC-53 and VIP36 21:110 Structural basis for disparate sugar-binding specificities in the homologous cargo receptors ERGIC-53 and VIP36. 24498414 1 78 theme secretory 276:284 arg1 pathway 286:292 the secretory pathway 272:292 the secretory pathway in animal cells 272:308 ERGIC-53 and VIP36 are categorized as leguminous type (L-type) lectins, and they function as cargo receptors for trafficking certain N-linked glycoproteins in the secretory pathway in animal cells. 24498414 1 79 gly glycoproteins 255:267 arg1 glycoproteins 255:267 trafficking certain N-linked glycoproteins 226:267 trafficking certain N-linked glycoproteins in the secretory pathway in animal cells 226:308 ERGIC-53 and VIP36 are categorized as leguminous type (L-type) lectins, and they function as cargo receptors for trafficking certain N-linked glycoproteins in the secretory pathway in animal cells. 24498414 3 80 theme presence 691:698 arg1 irrespective 671:682 irrespective 671:682 irrespective 671:682 VIP36 specifically interacts with the α1,2-linked D1 mannosyl arm without terminal glucosylation, while ERGIC-53 shows a broader specificity and lower binding affinity to the high-mannose-type oligosaccharides, irrespective of the presence or absence of the non-reducing terminal glucose residue at the D1 arm. 24498414 2 81 theme sugar-binding 416:428 arg1 specificities 430:442 distinct sugar-binding specificities 407:442 distinct sugar-binding specificities 407:442 They share structural similarities in their carbohydrate recognition domains (CRDs) but exhibit distinct sugar-binding specificities and affinities. 24498414 7 82 theme terminal 1315:1322 arg1 glucose 1324:1330 the non-reducing terminal glucose 1298:1330 the non-reducing terminal glucose of the D1 arm in its CRD 1298:1355 This enables ERGIC-53 to accommodate the non-reducing terminal glucose of the D1 arm in its CRD. 24498414 5 83 theme alternative 1048:1058 arg1 modes 1060:1064 two alternative modes 1044:1064 two alternative modes 1044:1064 ERGIC-53 can interact with the D1 trimannosyl arm in two alternative modes, one of which is similar but distinct from that previously observed for VIP36. 24498414 7 84 from glucose 1324:1330 arg1 CRD 1353:1355 its CRD 1349:1355 its CRD 1349:1355 This enables ERGIC-53 to accommodate the non-reducing terminal glucose of the D1 arm in its CRD. 24498414 4 85 theme ERGIC-53-CRD 825:836 arg1 structure 812:820 the crystal structure 800:820 the crystal structure of ERGIC-53-CRD in complex with their binding partner, MCFD2 and the α1,2 mannotriose which corresponds to the trisaccharide of the D1 arm of high-mannose-type glycans 800:988 In this study, we determined the crystal structure of ERGIC-53-CRD in complex with their binding partner, MCFD2 and the α1,2 mannotriose which corresponds to the trisaccharide of the D1 arm of high-mannose-type glycans. 24498414 3 86 theme absence 703:709 arg1 irrespective 671:682 irrespective 671:682 irrespective 671:682 VIP36 specifically interacts with the α1,2-linked D1 mannosyl arm without terminal glucosylation, while ERGIC-53 shows a broader specificity and lower binding affinity to the high-mannose-type oligosaccharides, irrespective of the presence or absence of the non-reducing terminal glucose residue at the D1 arm. 24498414 3 87 theme D1 510:511 arg1 arm 522:524 the α1,2-linked D1 mannosyl arm 494:524 the α1,2-linked D1 mannosyl arm 494:524 VIP36 specifically interacts with the α1,2-linked D1 mannosyl arm without terminal glucosylation, while ERGIC-53 shows a broader specificity and lower binding affinity to the high-mannose-type oligosaccharides, irrespective of the presence or absence of the non-reducing terminal glucose residue at the D1 arm. 24498414 5 88 theme trimannosyl 1025:1035 arg1 arm 1037:1039 the D1 trimannosyl arm 1018:1039 the D1 trimannosyl arm 1018:1039 ERGIC-53 can interact with the D1 trimannosyl arm in two alternative modes, one of which is similar but distinct from that previously observed for VIP36. 24498414 3 89 theme residue 748:754 arg1 presence 691:698 presence 691:698 presence 691:698 VIP36 specifically interacts with the α1,2-linked D1 mannosyl arm without terminal glucosylation, while ERGIC-53 shows a broader specificity and lower binding affinity to the high-mannose-type oligosaccharides, irrespective of the presence or absence of the non-reducing terminal glucose residue at the D1 arm. 24498414 3 89 theme residue 748:754 arg1 absence 703:709 absence 703:709 absence 703:709 VIP36 specifically interacts with the α1,2-linked D1 mannosyl arm without terminal glucosylation, while ERGIC-53 shows a broader specificity and lower binding affinity to the high-mannose-type oligosaccharides, irrespective of the presence or absence of the non-reducing terminal glucose residue at the D1 arm. 24498414 8 90 theme mannose 1420:1426 arg1 group 1398:1402 the 3-OH group 1389:1402 the 3-OH group of the terminal mannose 1389:1426 In the other interaction mode, the 3-OH group of the terminal mannose was situated outward with respect to the sugar binding pocket, also enabling the Glcα1-3 linkage formation without steric hindrance. 24498414 8 90 theme mannose 1420:1426 arg1 mannose 1420:1426 the terminal mannose 1407:1426 the terminal mannose 1407:1426 In the other interaction mode, the 3-OH group of the terminal mannose was situated outward with respect to the sugar binding pocket, also enabling the Glcα1-3 linkage formation without steric hindrance. 24498414 8 90 theme mannose 1420:1426 arg1 outward 1441:1447 outward 1441:1447 outward 1441:1447 In the other interaction mode, the 3-OH group of the terminal mannose was situated outward with respect to the sugar binding pocket, also enabling the Glcα1-3 linkage formation without steric hindrance. 24498414 2 91 theme recognition 368:378 arg1 CRDs 389:392 CRDs 389:392 CRDs 389:392 They share structural similarities in their carbohydrate recognition domains (CRDs) but exhibit distinct sugar-binding specificities and affinities. 24498414 2 91 theme recognition 368:378 arg1 domains 380:386 carbohydrate recognition domains 355:386 their carbohydrate recognition domains (CRDs) 349:393 They share structural similarities in their carbohydrate recognition domains (CRDs) but exhibit distinct sugar-binding specificities and affinities. 24498414 1 92 theme trafficking 226:236 arg1 glycoproteins 255:267 trafficking certain N-linked glycoproteins 226:267 trafficking certain N-linked glycoproteins in the secretory pathway in animal cells 226:308 ERGIC-53 and VIP36 are categorized as leguminous type (L-type) lectins, and they function as cargo receptors for trafficking certain N-linked glycoproteins in the secretory pathway in animal cells. 24399258 4 0 from implication 505:515 arg1 patients 536:543 patients 536:543 patients with gastric cancer 536:563 The implication of GnT-V status in patients with gastric cancer has not been studied extensively. 24399258 9 1 dep cell 1037:1040 arg1 proliferation 1042:1054 proliferation 1042:1054 proliferation 1042:1054 We characterized the function implication of GnT-V by cell proliferation and invasiveness analysis. 24399258 5 2 theme gastric 653:659 arg1 specimen 668:675 gastric cancer specimen 653:675 gastric cancer specimen 653:675 In the present study, we examined GnT-V expression in gastric cancer specimen both at protein and mRNA levels. 24399258 1 3 theme proteins 277:284 arg1 N-acetylglucosamine 196:214 N-acetylglucosamine 196:214 N-acetylglucosamine on asparagine (N)-linked oligosaccharides (N-glycan) of cell proteins 196:284 N-acetylglucosaminyltransferase V (GnT-V) is an enzyme that catalyzes β1-6 branching of N-acetylglucosamine on asparagine (N)-linked oligosaccharides (N-glycan) of cell proteins and the dysfunction of which is a common feature of various carcinomas. 24399258 12 4 theme proliferation 1433:1445 arg1 decrease 1416:1423 a decrease 1414:1423 a decrease of cell proliferation and invasiveness in SGC7901 and BGC 823 cells 1414:1491 Moreover, the downregulation of GnT-V expression by small interfering RNA resulted in a decrease of cell proliferation and invasiveness in SGC7901 and BGC 823 cells accompanied by morphological change. 24399258 13 5 from metastasis 1571:1580 arg1 cancer 1607:1612 gastric cancer 1599:1612 gastric cancer 1599:1612 This supports that GnT-V correlates with metastasis and prognosis in gastric cancer. 24399258 1 6 link -linked 233:239 arg1 N-glycan 259:266 N-glycan 259:266 N-glycan 259:266 N-acetylglucosaminyltransferase V (GnT-V) is an enzyme that catalyzes β1-6 branching of N-acetylglucosamine on asparagine (N)-linked oligosaccharides (N-glycan) of cell proteins and the dysfunction of which is a common feature of various carcinomas. 24399258 1 6 link -linked 233:239 arg1 oligosaccharides 241:256 asparagine (N)-linked oligosaccharides 219:256 asparagine (N)-linked oligosaccharides (N-glycan) 219:267 N-acetylglucosaminyltransferase V (GnT-V) is an enzyme that catalyzes β1-6 branching of N-acetylglucosamine on asparagine (N)-linked oligosaccharides (N-glycan) of cell proteins and the dysfunction of which is a common feature of various carcinomas. 24399258 14 7 from mechanisms 1685:1694 arg1 cancer 1727:1732 gastric cancer 1719:1732 gastric cancer with potential translational clinical applications 1719:1783 These results contribute to new insight into the underlying molecular mechanisms of GnT-V regulation in gastric cancer with potential translational clinical applications. 24399258 11 8 theme GnT-V 1227:1231 arg1 expression 1233:1242 positive GnT-V expression 1218:1242 positive GnT-V expression in gastric cancer 1218:1260 The overall survival time of positive GnT-V expression in gastric cancer was significantly shorter than that of negative GnT-V expression. 24399258 13 9 from prognosis 1586:1594 arg1 cancer 1607:1612 gastric cancer 1599:1612 gastric cancer 1599:1612 This supports that GnT-V correlates with metastasis and prognosis in gastric cancer. 24399258 14 10 theme translational 1749:1761 arg1 applications 1772:1783 potential translational clinical applications 1739:1783 potential translational clinical applications 1739:1783 These results contribute to new insight into the underlying molecular mechanisms of GnT-V regulation in gastric cancer with potential translational clinical applications. 24399258 12 11 theme interfering 1386:1396 arg1 RNA 1398:1400 small interfering RNA 1380:1400 small interfering RNA 1380:1400 Moreover, the downregulation of GnT-V expression by small interfering RNA resulted in a decrease of cell proliferation and invasiveness in SGC7901 and BGC 823 cells accompanied by morphological change. 24399258 14 12 theme new 1643:1645 arg1 insight 1647:1653 new insight 1643:1653 new insight into the underlying molecular mechanisms of GnT-V regulation in gastric cancer with potential translational clinical applications 1643:1783 These results contribute to new insight into the underlying molecular mechanisms of GnT-V regulation in gastric cancer with potential translational clinical applications. 24399258 13 13 theme gastric 1599:1605 arg1 cancer 1607:1612 gastric cancer 1599:1612 gastric cancer 1599:1612 This supports that GnT-V correlates with metastasis and prognosis in gastric cancer. 24399258 9 14 theme GnT-V 1028:1032 arg1 implication 1013:1023 the function implication 1000:1023 the function implication of GnT-V 1000:1032 We characterized the function implication of GnT-V by cell proliferation and invasiveness analysis. 24399258 1 15 from oligosaccharides 241:256 arg1 branching 183:191 β1-6 branching 178:191 β1-6 branching of N-acetylglucosamine on asparagine (N)-linked oligosaccharides (N-glycan) of cell proteins 178:284 N-acetylglucosaminyltransferase V (GnT-V) is an enzyme that catalyzes β1-6 branching of N-acetylglucosamine on asparagine (N)-linked oligosaccharides (N-glycan) of cell proteins and the dysfunction of which is a common feature of various carcinomas. 24399258 14 16 theme gastric 1719:1725 arg1 cancer 1727:1732 gastric cancer 1719:1732 gastric cancer with potential translational clinical applications 1719:1783 These results contribute to new insight into the underlying molecular mechanisms of GnT-V regulation in gastric cancer with potential translational clinical applications. 24399258 1 17 from N-acetylglucosamine 196:214 arg1 N-glycan 259:266 N-glycan 259:266 N-glycan 259:266 N-acetylglucosaminyltransferase V (GnT-V) is an enzyme that catalyzes β1-6 branching of N-acetylglucosamine on asparagine (N)-linked oligosaccharides (N-glycan) of cell proteins and the dysfunction of which is a common feature of various carcinomas. 24399258 1 17 from N-acetylglucosamine 196:214 arg1 oligosaccharides 241:256 asparagine (N)-linked oligosaccharides 219:256 asparagine (N)-linked oligosaccharides (N-glycan) 219:267 N-acetylglucosaminyltransferase V (GnT-V) is an enzyme that catalyzes β1-6 branching of N-acetylglucosamine on asparagine (N)-linked oligosaccharides (N-glycan) of cell proteins and the dysfunction of which is a common feature of various carcinomas. 24399258 12 18 theme GnT-V 1360:1364 arg1 expression 1366:1375 GnT-V expression 1360:1375 GnT-V expression 1360:1375 Moreover, the downregulation of GnT-V expression by small interfering RNA resulted in a decrease of cell proliferation and invasiveness in SGC7901 and BGC 823 cells accompanied by morphological change. 24399258 9 19 theme cell 1037:1040 arg1 analysis 1073:1080 cell proliferation and invasiveness analysis 1037:1080 cell proliferation and invasiveness analysis 1037:1080 We characterized the function implication of GnT-V by cell proliferation and invasiveness analysis. 24399258 14 20 theme regulation 1705:1714 arg1 mechanisms 1685:1694 the underlying molecular mechanisms 1660:1694 the underlying molecular mechanisms of GnT-V regulation in gastric cancer with potential translational clinical applications 1660:1783 These results contribute to new insight into the underlying molecular mechanisms of GnT-V regulation in gastric cancer with potential translational clinical applications. 24399258 1 21 from branching 183:191 arg1 N-glycan 259:266 N-glycan 259:266 N-glycan 259:266 N-acetylglucosaminyltransferase V (GnT-V) is an enzyme that catalyzes β1-6 branching of N-acetylglucosamine on asparagine (N)-linked oligosaccharides (N-glycan) of cell proteins and the dysfunction of which is a common feature of various carcinomas. 24399258 1 21 from branching 183:191 arg1 oligosaccharides 241:256 asparagine (N)-linked oligosaccharides 219:256 asparagine (N)-linked oligosaccharides (N-glycan) 219:267 N-acetylglucosaminyltransferase V (GnT-V) is an enzyme that catalyzes β1-6 branching of N-acetylglucosamine on asparagine (N)-linked oligosaccharides (N-glycan) of cell proteins and the dysfunction of which is a common feature of various carcinomas. 24399258 11 22 theme negative 1301:1308 arg1 expression 1316:1325 negative GnT-V expression 1301:1325 negative GnT-V expression 1301:1325 The overall survival time of positive GnT-V expression in gastric cancer was significantly shorter than that of negative GnT-V expression. 24399258 14 23 from cancer 1727:1732 arg1 mechanisms 1685:1694 the underlying molecular mechanisms 1660:1694 the underlying molecular mechanisms of GnT-V regulation in gastric cancer with potential translational clinical applications 1660:1783 These results contribute to new insight into the underlying molecular mechanisms of GnT-V regulation in gastric cancer with potential translational clinical applications. 24399258 1 24 theme various 338:344 arg1 carcinomas 346:355 various carcinomas 338:355 various carcinomas 338:355 N-acetylglucosaminyltransferase V (GnT-V) is an enzyme that catalyzes β1-6 branching of N-acetylglucosamine on asparagine (N)-linked oligosaccharides (N-glycan) of cell proteins and the dysfunction of which is a common feature of various carcinomas. 24399258 1 25 theme β1-6 178:181 arg1 branching 183:191 β1-6 branching 178:191 β1-6 branching of N-acetylglucosamine on asparagine (N)-linked oligosaccharides (N-glycan) of cell proteins 178:284 N-acetylglucosaminyltransferase V (GnT-V) is an enzyme that catalyzes β1-6 branching of N-acetylglucosamine on asparagine (N)-linked oligosaccharides (N-glycan) of cell proteins and the dysfunction of which is a common feature of various carcinomas. 24399258 0 26 from Expression 0:9 arg1 cancer 59:64 gastric cancer 51:64 gastric cancer 51:64 Expression of N-acetylglucosaminyltransferase V in gastric cancer correlates with metastasis and prognosis. 24399258 14 27 theme molecular 1675:1683 arg1 mechanisms 1685:1694 the underlying molecular mechanisms 1660:1694 the underlying molecular mechanisms of GnT-V regulation in gastric cancer with potential translational clinical applications 1660:1783 These results contribute to new insight into the underlying molecular mechanisms of GnT-V regulation in gastric cancer with potential translational clinical applications. 24399258 11 28 theme survival 1201:1208 arg1 shorter 1280:1286 shorter 1280:1286 shorter 1280:1286 The overall survival time of positive GnT-V expression in gastric cancer was significantly shorter than that of negative GnT-V expression. 24399258 11 28 theme survival 1201:1208 arg1 time 1210:1213 The overall survival time 1189:1213 The overall survival time of positive GnT-V expression in gastric cancer 1189:1260 The overall survival time of positive GnT-V expression in gastric cancer was significantly shorter than that of negative GnT-V expression. 24399258 8 29 theme small 877:881 arg1 RNA 895:897 the small interfering RNA 873:897 the small interfering RNA 873:897 Furthermore, the small interfering RNA was devised to downregulate the GnT-V mRNA expression in SGC7901 and BGC 823 cells. 24399258 11 30 from cancer 1255:1260 arg1 shorter 1280:1286 shorter 1280:1286 shorter 1280:1286 The overall survival time of positive GnT-V expression in gastric cancer was significantly shorter than that of negative GnT-V expression. 24399258 11 30 from cancer 1255:1260 arg1 time 1210:1213 The overall survival time 1189:1213 The overall survival time of positive GnT-V expression in gastric cancer 1189:1260 The overall survival time of positive GnT-V expression in gastric cancer was significantly shorter than that of negative GnT-V expression. 24399258 1 31 theme N-acetylglucosaminyltransferase 108:138 arg1 GnT-V 143:147 GnT-V 143:147 GnT-V 143:147 N-acetylglucosaminyltransferase V (GnT-V) is an enzyme that catalyzes β1-6 branching of N-acetylglucosamine on asparagine (N)-linked oligosaccharides (N-glycan) of cell proteins and the dysfunction of which is a common feature of various carcinomas. 24399258 1 31 theme N-acetylglucosaminyltransferase 108:138 arg1 V 140:140 N-acetylglucosaminyltransferase V 108:140 N-acetylglucosaminyltransferase V (GnT-V) 108:148 N-acetylglucosaminyltransferase V (GnT-V) is an enzyme that catalyzes β1-6 branching of N-acetylglucosamine on asparagine (N)-linked oligosaccharides (N-glycan) of cell proteins and the dysfunction of which is a common feature of various carcinomas. 24399258 1 31 theme N-acetylglucosaminyltransferase 108:138 arg1 enzyme 156:161 an enzyme 153:161 an enzyme that catalyzes β1-6 branching of N-acetylglucosamine on asparagine (N)-linked oligosaccharides (N-glycan) of cell proteins and the dysfunction of which is a common feature of various carcinomas 153:355 N-acetylglucosaminyltransferase V (GnT-V) is an enzyme that catalyzes β1-6 branching of N-acetylglucosamine on asparagine (N)-linked oligosaccharides (N-glycan) of cell proteins and the dysfunction of which is a common feature of various carcinomas. 24399258 11 32 theme gastric 1247:1253 arg1 cancer 1255:1260 gastric cancer 1247:1260 gastric cancer 1247:1260 The overall survival time of positive GnT-V expression in gastric cancer was significantly shorter than that of negative GnT-V expression. 24399258 0 33 theme N-acetylglucosaminyltransferase 14:44 arg1 V 46:46 N-acetylglucosaminyltransferase V 14:46 N-acetylglucosaminyltransferase V 14:46 Expression of N-acetylglucosaminyltransferase V in gastric cancer correlates with metastasis and prognosis. 24399258 7 34 theme survival 792:799 arg1 curves 801:806 Kaplan-Meier survival curves 779:806 Kaplan-Meier survival curves 779:806 Kaplan-Meier survival curves were generated to show the cause-specific survival. 24399258 14 35 with cancer 1727:1732 arg1 applications 1772:1783 potential translational clinical applications 1739:1783 potential translational clinical applications 1739:1783 These results contribute to new insight into the underlying molecular mechanisms of GnT-V regulation in gastric cancer with potential translational clinical applications. 24399258 11 36 theme expression 1233:1242 arg1 shorter 1280:1286 shorter 1280:1286 shorter 1280:1286 The overall survival time of positive GnT-V expression in gastric cancer was significantly shorter than that of negative GnT-V expression. 24399258 11 36 theme expression 1233:1242 arg1 time 1210:1213 The overall survival time 1189:1213 The overall survival time of positive GnT-V expression in gastric cancer 1189:1260 The overall survival time of positive GnT-V expression in gastric cancer was significantly shorter than that of negative GnT-V expression. 24399258 3 37 theme GnT-V 452:456 arg1 expression 458:467 GnT-V expression 452:467 GnT-V expression 452:467 Therefore, the clinical implication of GnT-V expression may differ in each cancer type. 24399258 1 38 theme which 309:313 arg1 dysfunction 294:304 the dysfunction 290:304 the dysfunction 290:304 N-acetylglucosaminyltransferase V (GnT-V) is an enzyme that catalyzes β1-6 branching of N-acetylglucosamine on asparagine (N)-linked oligosaccharides (N-glycan) of cell proteins and the dysfunction of which is a common feature of various carcinomas. 24399258 1 38 theme which 309:313 arg1 feature 327:333 a common feature 318:333 a common feature of various carcinomas 318:355 N-acetylglucosaminyltransferase V (GnT-V) is an enzyme that catalyzes β1-6 branching of N-acetylglucosamine on asparagine (N)-linked oligosaccharides (N-glycan) of cell proteins and the dysfunction of which is a common feature of various carcinomas. 24399258 8 39 theme GnT-V 931:935 arg1 expression 942:951 the GnT-V mRNA expression 927:951 the GnT-V mRNA expression in SGC7901 and BGC 823 cells 927:980 Furthermore, the small interfering RNA was devised to downregulate the GnT-V mRNA expression in SGC7901 and BGC 823 cells. 24399258 4 40 theme GnT-V 520:524 arg1 status 526:531 GnT-V status 520:531 GnT-V status 520:531 The implication of GnT-V status in patients with gastric cancer has not been studied extensively. 24399258 6 41 theme clinical 744:751 arg1 variables 768:776 clinical and pathologic variables 744:776 clinical and pathologic variables 744:776 We compared GnT-V expression with clinical and pathologic variables. 24399258 3 42 theme cancer 488:493 arg1 type 495:498 each cancer type 483:498 each cancer type 483:498 Therefore, the clinical implication of GnT-V expression may differ in each cancer type. 24399258 10 43 theme gastric 1095:1101 arg1 specimen 1110:1117 gastric cancer specimen 1095:1117 gastric cancer specimen 1095:1117 Analysis in gastric cancer specimen revealed that GnT-V expression correlated with tumor grade and stage. 24399258 12 44 dep resulted 1402:1409 arg1 accompanied 1493:1503 accompanied 1493:1503 accompanied by morphological change 1493:1527 Moreover, the downregulation of GnT-V expression by small interfering RNA resulted in a decrease of cell proliferation and invasiveness in SGC7901 and BGC 823 cells accompanied by morphological change. 24399258 1 45 theme -linked 233:239 arg1 N-glycan 259:266 N-glycan 259:266 N-glycan 259:266 N-acetylglucosaminyltransferase V (GnT-V) is an enzyme that catalyzes β1-6 branching of N-acetylglucosamine on asparagine (N)-linked oligosaccharides (N-glycan) of cell proteins and the dysfunction of which is a common feature of various carcinomas. 24399258 1 45 theme -linked 233:239 arg1 oligosaccharides 241:256 asparagine (N)-linked oligosaccharides 219:256 asparagine (N)-linked oligosaccharides (N-glycan) 219:267 N-acetylglucosaminyltransferase V (GnT-V) is an enzyme that catalyzes β1-6 branching of N-acetylglucosamine on asparagine (N)-linked oligosaccharides (N-glycan) of cell proteins and the dysfunction of which is a common feature of various carcinomas. 24399258 8 46 theme SGC7901 956:962 arg1 cells 976:980 SGC7901 and BGC 823 cells 956:980 SGC7901 and BGC 823 cells 956:980 Furthermore, the small interfering RNA was devised to downregulate the GnT-V mRNA expression in SGC7901 and BGC 823 cells. 24399258 12 47 theme BGC 1479:1481 arg1 cells 1487:1491 SGC7901 and BGC 823 cells 1467:1491 SGC7901 and BGC 823 cells 1467:1491 Moreover, the downregulation of GnT-V expression by small interfering RNA resulted in a decrease of cell proliferation and invasiveness in SGC7901 and BGC 823 cells accompanied by morphological change. 24399258 8 48 theme BGC 968:970 arg1 cells 976:980 SGC7901 and BGC 823 cells 956:980 SGC7901 and BGC 823 cells 956:980 Furthermore, the small interfering RNA was devised to downregulate the GnT-V mRNA expression in SGC7901 and BGC 823 cells. 24399258 5 49 theme GnT-V 633:637 arg1 expression 639:648 GnT-V expression 633:648 GnT-V expression in gastric cancer specimen both at protein and mRNA levels 633:707 In the present study, we examined GnT-V expression in gastric cancer specimen both at protein and mRNA levels. 24399258 11 50 from expression 1233:1242 arg1 cancer 1255:1260 gastric cancer 1247:1260 gastric cancer 1247:1260 The overall survival time of positive GnT-V expression in gastric cancer was significantly shorter than that of negative GnT-V expression. 24399258 14 51 from regulation 1705:1714 arg1 cancer 1727:1732 gastric cancer 1719:1732 gastric cancer with potential translational clinical applications 1719:1783 These results contribute to new insight into the underlying molecular mechanisms of GnT-V regulation in gastric cancer with potential translational clinical applications. 24399258 1 52 theme cell 272:275 arg1 proteins 277:284 cell proteins 272:284 cell proteins 272:284 N-acetylglucosaminyltransferase V (GnT-V) is an enzyme that catalyzes β1-6 branching of N-acetylglucosamine on asparagine (N)-linked oligosaccharides (N-glycan) of cell proteins and the dysfunction of which is a common feature of various carcinomas. 24399258 12 53 theme invasiveness 1451:1462 arg1 decrease 1416:1423 a decrease 1414:1423 a decrease of cell proliferation and invasiveness in SGC7901 and BGC 823 cells 1414:1491 Moreover, the downregulation of GnT-V expression by small interfering RNA resulted in a decrease of cell proliferation and invasiveness in SGC7901 and BGC 823 cells accompanied by morphological change. 24399258 12 54 theme SGC7901 1467:1473 arg1 cells 1487:1491 SGC7901 and BGC 823 cells 1467:1491 SGC7901 and BGC 823 cells 1467:1491 Moreover, the downregulation of GnT-V expression by small interfering RNA resulted in a decrease of cell proliferation and invasiveness in SGC7901 and BGC 823 cells accompanied by morphological change. 24399258 12 55 theme cell 1428:1431 arg1 proliferation 1433:1445 cell proliferation 1428:1445 cell proliferation 1428:1445 Moreover, the downregulation of GnT-V expression by small interfering RNA resulted in a decrease of cell proliferation and invasiveness in SGC7901 and BGC 823 cells accompanied by morphological change. 24399258 4 56 with patients 536:543 arg1 cancer 558:563 gastric cancer 550:563 gastric cancer 550:563 The implication of GnT-V status in patients with gastric cancer has not been studied extensively. 24399258 1 57 theme N-acetylglucosamine 196:214 arg1 branching 183:191 β1-6 branching 178:191 β1-6 branching of N-acetylglucosamine on asparagine (N)-linked oligosaccharides (N-glycan) of cell proteins 178:284 N-acetylglucosaminyltransferase V (GnT-V) is an enzyme that catalyzes β1-6 branching of N-acetylglucosamine on asparagine (N)-linked oligosaccharides (N-glycan) of cell proteins and the dysfunction of which is a common feature of various carcinomas. 24399258 5 58 theme protein 685:691 arg1 levels 702:707 protein and mRNA levels 685:707 levels 702:707 In the present study, we examined GnT-V expression in gastric cancer specimen both at protein and mRNA levels. 24399258 6 59 theme pathologic 757:766 arg1 variables 768:776 clinical and pathologic variables 744:776 clinical and pathologic variables 744:776 We compared GnT-V expression with clinical and pathologic variables. 24399258 7 60 theme cause-specific 835:848 arg1 survival 850:857 the cause-specific survival 831:857 the cause-specific survival 831:857 Kaplan-Meier survival curves were generated to show the cause-specific survival. 24399258 12 61 from decrease 1416:1423 arg1 cells 1487:1491 SGC7901 and BGC 823 cells 1467:1491 SGC7901 and BGC 823 cells 1467:1491 Moreover, the downregulation of GnT-V expression by small interfering RNA resulted in a decrease of cell proliferation and invasiveness in SGC7901 and BGC 823 cells accompanied by morphological change. 24399258 5 62 theme mRNA 697:700 arg1 levels 702:707 protein and mRNA levels 685:707 levels 702:707 In the present study, we examined GnT-V expression in gastric cancer specimen both at protein and mRNA levels. 24399258 14 63 theme clinical 1763:1770 arg1 applications 1772:1783 potential translational clinical applications 1739:1783 potential translational clinical applications 1739:1783 These results contribute to new insight into the underlying molecular mechanisms of GnT-V regulation in gastric cancer with potential translational clinical applications. 24399258 12 64 theme expression 1366:1375 arg1 downregulation 1342:1355 the downregulation 1338:1355 the downregulation of GnT-V expression by small interfering RNA 1338:1400 Moreover, the downregulation of GnT-V expression by small interfering RNA resulted in a decrease of cell proliferation and invasiveness in SGC7901 and BGC 823 cells accompanied by morphological change. 24399258 1 65 theme common 320:325 arg1 dysfunction 294:304 the dysfunction 290:304 the dysfunction 290:304 N-acetylglucosaminyltransferase V (GnT-V) is an enzyme that catalyzes β1-6 branching of N-acetylglucosamine on asparagine (N)-linked oligosaccharides (N-glycan) of cell proteins and the dysfunction of which is a common feature of various carcinomas. 24399258 1 65 theme common 320:325 arg1 feature 327:333 a common feature 318:333 a common feature of various carcinomas 318:355 N-acetylglucosaminyltransferase V (GnT-V) is an enzyme that catalyzes β1-6 branching of N-acetylglucosamine on asparagine (N)-linked oligosaccharides (N-glycan) of cell proteins and the dysfunction of which is a common feature of various carcinomas. 24399258 9 66 theme function 1004:1011 arg1 implication 1013:1023 the function implication 1000:1023 the function implication of GnT-V 1000:1032 We characterized the function implication of GnT-V by cell proliferation and invasiveness analysis. 24399258 5 67 theme cancer 661:666 arg1 specimen 668:675 gastric cancer specimen 653:675 gastric cancer specimen 653:675 In the present study, we examined GnT-V expression in gastric cancer specimen both at protein and mRNA levels. 24399258 14 68 theme potential 1739:1747 arg1 applications 1772:1783 potential translational clinical applications 1739:1783 potential translational clinical applications 1739:1783 These results contribute to new insight into the underlying molecular mechanisms of GnT-V regulation in gastric cancer with potential translational clinical applications. 24399258 12 69 theme small 1380:1384 arg1 RNA 1398:1400 small interfering RNA 1380:1400 small interfering RNA 1380:1400 Moreover, the downregulation of GnT-V expression by small interfering RNA resulted in a decrease of cell proliferation and invasiveness in SGC7901 and BGC 823 cells accompanied by morphological change. 24399258 11 70 from time 1210:1213 arg1 cancer 1255:1260 gastric cancer 1247:1260 gastric cancer 1247:1260 The overall survival time of positive GnT-V expression in gastric cancer was significantly shorter than that of negative GnT-V expression. 24399258 10 71 theme tumor 1166:1170 arg1 grade 1172:1176 tumor grade 1166:1176 tumor grade 1166:1176 Analysis in gastric cancer specimen revealed that GnT-V expression correlated with tumor grade and stage. 24399258 14 72 theme GnT-V 1699:1703 arg1 regulation 1705:1714 GnT-V regulation 1699:1714 GnT-V regulation in gastric cancer with potential translational clinical applications 1699:1783 These results contribute to new insight into the underlying molecular mechanisms of GnT-V regulation in gastric cancer with potential translational clinical applications. 24399258 11 73 theme GnT-V 1310:1314 arg1 expression 1316:1325 negative GnT-V expression 1301:1325 negative GnT-V expression 1301:1325 The overall survival time of positive GnT-V expression in gastric cancer was significantly shorter than that of negative GnT-V expression. 24399258 9 74 theme invasiveness 1060:1071 arg1 analysis 1073:1080 cell proliferation and invasiveness analysis 1037:1080 cell proliferation and invasiveness analysis 1037:1080 We characterized the function implication of GnT-V by cell proliferation and invasiveness analysis. 24399258 1 75 theme carcinomas 346:355 arg1 dysfunction 294:304 the dysfunction 290:304 the dysfunction 290:304 N-acetylglucosaminyltransferase V (GnT-V) is an enzyme that catalyzes β1-6 branching of N-acetylglucosamine on asparagine (N)-linked oligosaccharides (N-glycan) of cell proteins and the dysfunction of which is a common feature of various carcinomas. 24399258 1 75 theme carcinomas 346:355 arg1 feature 327:333 a common feature 318:333 a common feature of various carcinomas 318:355 N-acetylglucosaminyltransferase V (GnT-V) is an enzyme that catalyzes β1-6 branching of N-acetylglucosamine on asparagine (N)-linked oligosaccharides (N-glycan) of cell proteins and the dysfunction of which is a common feature of various carcinomas. 24399258 11 76 theme overall 1193:1199 arg1 shorter 1280:1286 shorter 1280:1286 shorter 1280:1286 The overall survival time of positive GnT-V expression in gastric cancer was significantly shorter than that of negative GnT-V expression. 24399258 11 76 theme overall 1193:1199 arg1 time 1210:1213 The overall survival time 1189:1213 The overall survival time of positive GnT-V expression in gastric cancer 1189:1260 The overall survival time of positive GnT-V expression in gastric cancer was significantly shorter than that of negative GnT-V expression. 24399258 14 77 theme underlying 1664:1673 arg1 mechanisms 1685:1694 the underlying molecular mechanisms 1660:1694 the underlying molecular mechanisms of GnT-V regulation in gastric cancer with potential translational clinical applications 1660:1783 These results contribute to new insight into the underlying molecular mechanisms of GnT-V regulation in gastric cancer with potential translational clinical applications. 24399258 5 78 theme present 606:612 arg1 study 614:618 the present study 602:618 the present study 602:618 In the present study, we examined GnT-V expression in gastric cancer specimen both at protein and mRNA levels. 24399258 8 79 from expression 942:951 arg1 cells 976:980 SGC7901 and BGC 823 cells 956:980 SGC7901 and BGC 823 cells 956:980 Furthermore, the small interfering RNA was devised to downregulate the GnT-V mRNA expression in SGC7901 and BGC 823 cells. 24399258 5 80 dep specimen 668:675 arg1 both 677:680 both 677:680 both 677:680 In the present study, we examined GnT-V expression in gastric cancer specimen both at protein and mRNA levels. 24399258 2 81 theme GnT-V 384:388 arg1 role 376:379 the role 372:379 the role of GnT-V 372:388 Nevertheless, the role of GnT-V remains controversial. 24399258 10 82 from Analysis 1083:1090 arg1 specimen 1110:1117 gastric cancer specimen 1095:1117 gastric cancer specimen 1095:1117 Analysis in gastric cancer specimen revealed that GnT-V expression correlated with tumor grade and stage. 24399258 10 83 theme cancer 1103:1108 arg1 specimen 1110:1117 gastric cancer specimen 1095:1117 gastric cancer specimen 1095:1117 Analysis in gastric cancer specimen revealed that GnT-V expression correlated with tumor grade and stage. 24399258 11 84 theme positive 1218:1225 arg1 expression 1233:1242 positive GnT-V expression 1218:1242 positive GnT-V expression in gastric cancer 1218:1260 The overall survival time of positive GnT-V expression in gastric cancer was significantly shorter than that of negative GnT-V expression. 24399258 8 85 theme interfering 883:893 arg1 RNA 895:897 the small interfering RNA 873:897 the small interfering RNA 873:897 Furthermore, the small interfering RNA was devised to downregulate the GnT-V mRNA expression in SGC7901 and BGC 823 cells. 24399258 4 86 theme gastric 550:556 arg1 cancer 558:563 gastric cancer 550:563 gastric cancer 550:563 The implication of GnT-V status in patients with gastric cancer has not been studied extensively. 24399258 3 87 theme clinical 428:435 arg1 implication 437:447 the clinical implication 424:447 the clinical implication of GnT-V expression 424:467 Therefore, the clinical implication of GnT-V expression may differ in each cancer type. 24399258 0 88 theme V 46:46 arg1 Expression 0:9 Expression 0:9 Expression of N-acetylglucosaminyltransferase V in gastric cancer 0:64 Expression of N-acetylglucosaminyltransferase V in gastric cancer correlates with metastasis and prognosis. 24399258 0 89 theme gastric 51:57 arg1 cancer 59:64 gastric cancer 51:64 gastric cancer 51:64 Expression of N-acetylglucosaminyltransferase V in gastric cancer correlates with metastasis and prognosis. 24399258 10 90 theme GnT-V 1133:1137 arg1 expression 1139:1148 GnT-V expression 1133:1148 GnT-V expression 1133:1148 Analysis in gastric cancer specimen revealed that GnT-V expression correlated with tumor grade and stage. 24399258 4 91 theme status 526:531 arg1 implication 505:515 The implication 501:515 The implication of GnT-V status in patients with gastric cancer 501:563 The implication of GnT-V status in patients with gastric cancer has not been studied extensively. 24399258 3 92 theme expression 458:467 arg1 implication 437:447 the clinical implication 424:447 the clinical implication of GnT-V expression 424:467 Therefore, the clinical implication of GnT-V expression may differ in each cancer type. 24399258 7 93 theme Kaplan-Meier 779:790 arg1 curves 801:806 Kaplan-Meier survival curves 779:806 Kaplan-Meier survival curves 779:806 Kaplan-Meier survival curves were generated to show the cause-specific survival. 24399258 5 94 from expression 639:648 arg1 specimen 668:675 gastric cancer specimen 653:675 gastric cancer specimen 653:675 In the present study, we examined GnT-V expression in gastric cancer specimen both at protein and mRNA levels. 24399258 8 95 theme mRNA 937:940 arg1 expression 942:951 the GnT-V mRNA expression 927:951 the GnT-V mRNA expression in SGC7901 and BGC 823 cells 927:980 Furthermore, the small interfering RNA was devised to downregulate the GnT-V mRNA expression in SGC7901 and BGC 823 cells. 24399258 6 96 theme GnT-V 722:726 arg1 expression 728:737 GnT-V expression 722:737 GnT-V expression 722:737 We compared GnT-V expression with clinical and pathologic variables. 24399258 12 97 theme morphological 1508:1520 arg1 change 1522:1527 morphological change 1508:1527 morphological change 1508:1527 Moreover, the downregulation of GnT-V expression by small interfering RNA resulted in a decrease of cell proliferation and invasiveness in SGC7901 and BGC 823 cells accompanied by morphological change. 27010859 10 0 theme mTOR 1548:1551 arg1 4EBP1 1582:1586 4EBP1 1582:1586 4EBP1 1582:1586 Indeed, LPA prevented mESCs from undergoing hypoxia-induced apoptosis and increased phosphorylation of mTOR and its substrates (S6K1 and 4EBP1). 27010859 10 0 theme mTOR 1548:1551 arg1 S6K1 1573:1576 S6K1 1573:1576 S6K1 1573:1576 Indeed, LPA prevented mESCs from undergoing hypoxia-induced apoptosis and increased phosphorylation of mTOR and its substrates (S6K1 and 4EBP1). 27010859 10 0 theme mTOR 1548:1551 arg1 substrates 1561:1570 its substrates 1557:1570 its substrates (S6K1 and 4EBP1) 1557:1587 Indeed, LPA prevented mESCs from undergoing hypoxia-induced apoptosis and increased phosphorylation of mTOR and its substrates (S6K1 and 4EBP1). 27010859 10 0 theme mTOR 1548:1551 arg1 phosphorylation 1529:1543 phosphorylation 1529:1543 phosphorylation of mTOR 1529:1551 Indeed, LPA prevented mESCs from undergoing hypoxia-induced apoptosis and increased phosphorylation of mTOR and its substrates (S6K1 and 4EBP1). 27010859 2 1 theme cells 401:405 arg1 O-GlcNAcylation 376:390 O-GlcNAcylation 376:390 O-GlcNAcylation 376:390 Hypoxia activates O-linked β-N-acetyl glucosaminylation (O-GlcNAcylation) of stem cells, which contributes to regulation of cellular metabolism, as well as cell fate. 27010859 2 1 theme cells 401:405 arg1 glucosaminylation 357:373 O-linked β-N-acetyl glucosaminylation 337:373 O-linked β-N-acetyl glucosaminylation (O-GlcNAcylation) 337:391 Hypoxia activates O-linked β-N-acetyl glucosaminylation (O-GlcNAcylation) of stem cells, which contributes to regulation of cellular metabolism, as well as cell fate. 27010859 11 2 theme pro-apoptotic 1658:1670 arg1 proteins 1672:1679 pro-apoptotic proteins 1658:1679 pro-apoptotic proteins 1658:1679 Moreover, mTOR inactivation by rapamycin (mTOR inhibitor) increased pro-apoptotic proteins expressions and mESC apoptosis. 27010859 1 3 theme cell 305:308 arg1 therapy 310:316 stem cell therapy 300:316 stem cell therapy 300:316 Oxygen signaling is critical for stem cell regulation, and oxidative stress-induced stem cell apoptosis decreases the efficiency of stem cell therapy. 27010859 9 4 from anti-apoptosis 1355:1368 arg1 mESCs 1373:1377 mESCs 1373:1377 mESCs 1373:1377 Silencing of GPAT1 by gpat1 siRNA transfection reduced glucosamine-mediated anti-apoptosis in mESCs and reduced mammalian target of rapamycin (mTOR) phosphorylation. 27010859 7 5 dep regulated 945:953 arg1 whereas 988:994 whereas 988:994 whereas 988:994 In addition, hypoxia regulated several lipid metabolic enzymes, whereas glucosamine increased expression of glycerol-3-phosphate acyltransferase-1 (GPAT1), a lipid metabolic enzyme producing lysophosphatidic acid (LPA). 27010859 3 6 theme hypoxia-induced 574:588 arg1 apoptosis 590:598 hypoxia-induced apoptosis 574:598 hypoxia-induced apoptosis of mouse embryonic stem cells (mESCs) 574:636 Our study investigated the role of O-GlcNAcylation via glucosamine in the protection of hypoxia-induced apoptosis of mouse embryonic stem cells (mESCs). 27010859 1 7 theme cell 206:209 arg1 regulation 211:220 stem cell regulation 201:220 stem cell regulation 201:220 Oxygen signaling is critical for stem cell regulation, and oxidative stress-induced stem cell apoptosis decreases the efficiency of stem cell therapy. 27010859 13 8 theme glucosamine 1930:1940 arg1 effects 1942:1948 those glucosamine effects 1924:1948 those glucosamine effects 1924:1948 Conversely, silencing of GPAT1 expression reversed those glucosamine effects. 27010859 6 9 theme mESC 851:854 arg1 apoptosis 856:864 hypoxia-induced mESC apoptosis 835:864 hypoxia-induced mESC apoptosis 835:864 Glucosamine treatment further enhanced the O-GlcNAc level and prevented hypoxia-induced mESC apoptosis, which was suppressed by O-GlcNAc transferase inhibitors. 27010859 3 10 theme cells 624:628 arg1 apoptosis 590:598 hypoxia-induced apoptosis 574:598 hypoxia-induced apoptosis of mouse embryonic stem cells (mESCs) 574:636 Our study investigated the role of O-GlcNAcylation via glucosamine in the protection of hypoxia-induced apoptosis of mouse embryonic stem cells (mESCs). 27010859 14 11 theme apoptosis 2093:2101 arg1 inhibition 2058:2067 inhibition 2058:2067 inhibition of hypoxia-induced mESC apoptosis 2058:2101 In conclusion, enhancing O-GlcNAcylation of Sp1 by glucosamine stimulates GPAT1 expression, which leads to inhibition of hypoxia-induced mESC apoptosis via mTOR activation. 27010859 12 12 theme siRNA 1759:1763 arg1 transplantation 1726:1740 transplantation 1726:1740 transplantation of non-targeting siRNA and glucosamine-treated mESCs 1726:1793 Furthermore, transplantation of non-targeting siRNA and glucosamine-treated mESCs increased cell survival and inhibited flap necrosis in mouse skin flap model. 27010859 0 13 theme mTOR 151:154 arg1 activation 156:165 mTOR activation 151:165 mTOR activation 151:165 Glycerol-3-phosphate acyltransferase-1 upregulation by O-GlcNAcylation of Sp1 protects against hypoxia-induced mouse embryonic stem cell apoptosis via mTOR activation. 27010859 3 14 theme embryonic 609:617 arg1 mESCs 631:635 mESCs 631:635 mESCs 631:635 Our study investigated the role of O-GlcNAcylation via glucosamine in the protection of hypoxia-induced apoptosis of mouse embryonic stem cells (mESCs). 27010859 3 14 theme embryonic 609:617 arg1 cells 624:628 mouse embryonic stem cells 603:628 mouse embryonic stem cells (mESCs) 603:636 Our study investigated the role of O-GlcNAcylation via glucosamine in the protection of hypoxia-induced apoptosis of mouse embryonic stem cells (mESCs). 27010859 14 15 theme hypoxia-induced 2072:2086 arg1 apoptosis 2093:2101 hypoxia-induced mESC apoptosis 2072:2101 hypoxia-induced mESC apoptosis 2072:2101 In conclusion, enhancing O-GlcNAcylation of Sp1 by glucosamine stimulates GPAT1 expression, which leads to inhibition of hypoxia-induced mESC apoptosis via mTOR activation. 27010859 12 16 theme glucosamine-treated 1769:1787 arg1 mESCs 1789:1793 glucosamine-treated mESCs 1769:1793 glucosamine-treated mESCs 1769:1793 Furthermore, transplantation of non-targeting siRNA and glucosamine-treated mESCs increased cell survival and inhibited flap necrosis in mouse skin flap model. 27010859 13 17 theme GPAT1 1898:1902 arg1 expression 1904:1913 GPAT1 expression 1898:1913 GPAT1 expression 1898:1913 Conversely, silencing of GPAT1 expression reversed those glucosamine effects. 27010859 7 18 theme lysophosphatidic 1115:1130 arg1 LPA 1138:1140 LPA 1138:1140 LPA 1138:1140 In addition, hypoxia regulated several lipid metabolic enzymes, whereas glucosamine increased expression of glycerol-3-phosphate acyltransferase-1 (GPAT1), a lipid metabolic enzyme producing lysophosphatidic acid (LPA). 27010859 7 18 theme lysophosphatidic 1115:1130 arg1 acid 1132:1135 lysophosphatidic acid 1115:1135 lysophosphatidic acid (LPA) 1115:1141 In addition, hypoxia regulated several lipid metabolic enzymes, whereas glucosamine increased expression of glycerol-3-phosphate acyltransferase-1 (GPAT1), a lipid metabolic enzyme producing lysophosphatidic acid (LPA). 27010859 1 19 theme stem 252:255 arg1 apoptosis 262:270 oxidative stress-induced stem cell apoptosis 227:270 oxidative stress-induced stem cell apoptosis 227:270 Oxygen signaling is critical for stem cell regulation, and oxidative stress-induced stem cell apoptosis decreases the efficiency of stem cell therapy. 27010859 8 20 dep O-GlcNAcylation 1179:1193 arg1 addition 1147:1154 addition 1147:1154 addition 1147:1154 In addition, glucosamine-increased O-GlcNAcylation of Sp1, which subsequently leads to Sp1 nuclear translocation and GPAT1 expression. 27010859 7 21 theme lipid 1082:1086 arg1 acyltransferase-1 1053:1069 glycerol-3-phosphate acyltransferase-1 1032:1069 glycerol-3-phosphate acyltransferase-1 (GPAT1) 1032:1077 In addition, hypoxia regulated several lipid metabolic enzymes, whereas glucosamine increased expression of glycerol-3-phosphate acyltransferase-1 (GPAT1), a lipid metabolic enzyme producing lysophosphatidic acid (LPA). 27010859 7 21 theme lipid 1082:1086 arg1 enzyme 1098:1103 a lipid metabolic enzyme 1080:1103 a lipid metabolic enzyme producing lysophosphatidic acid (LPA) 1080:1141 In addition, hypoxia regulated several lipid metabolic enzymes, whereas glucosamine increased expression of glycerol-3-phosphate acyltransferase-1 (GPAT1), a lipid metabolic enzyme producing lysophosphatidic acid (LPA). 27010859 1 22 theme Oxygen 168:173 arg1 signaling 175:183 Oxygen signaling 168:183 Oxygen signaling 168:183 Oxygen signaling is critical for stem cell regulation, and oxidative stress-induced stem cell apoptosis decreases the efficiency of stem cell therapy. 27010859 9 23 theme rapamycin 1411:1419 arg1 phosphorylation 1428:1442 rapamycin (mTOR) phosphorylation 1411:1442 rapamycin (mTOR) phosphorylation 1411:1442 Silencing of GPAT1 by gpat1 siRNA transfection reduced glucosamine-mediated anti-apoptosis in mESCs and reduced mammalian target of rapamycin (mTOR) phosphorylation. 27010859 14 24 theme GPAT1 2025:2029 arg1 expression 2031:2040 GPAT1 expression 2025:2040 GPAT1 expression 2025:2040 In conclusion, enhancing O-GlcNAcylation of Sp1 by glucosamine stimulates GPAT1 expression, which leads to inhibition of hypoxia-induced mESC apoptosis via mTOR activation. 27010859 12 25 theme skin 1856:1859 arg1 model 1866:1870 mouse skin flap model 1850:1870 mouse skin flap model 1850:1870 Furthermore, transplantation of non-targeting siRNA and glucosamine-treated mESCs increased cell survival and inhibited flap necrosis in mouse skin flap model. 27010859 0 26 theme mouse 111:115 arg1 apoptosis 137:145 hypoxia-induced mouse embryonic stem cell apoptosis 95:145 hypoxia-induced mouse embryonic stem cell apoptosis 95:145 Glycerol-3-phosphate acyltransferase-1 upregulation by O-GlcNAcylation of Sp1 protects against hypoxia-induced mouse embryonic stem cell apoptosis via mTOR activation. 27010859 0 27 theme stem 127:130 arg1 apoptosis 137:145 hypoxia-induced mouse embryonic stem cell apoptosis 95:145 hypoxia-induced mouse embryonic stem cell apoptosis 95:145 Glycerol-3-phosphate acyltransferase-1 upregulation by O-GlcNAcylation of Sp1 protects against hypoxia-induced mouse embryonic stem cell apoptosis via mTOR activation. 27010859 9 28 theme phosphorylation 1428:1442 arg1 target 1401:1406 mammalian target 1391:1406 mammalian target of rapamycin (mTOR) phosphorylation 1391:1442 Silencing of GPAT1 by gpat1 siRNA transfection reduced glucosamine-mediated anti-apoptosis in mESCs and reduced mammalian target of rapamycin (mTOR) phosphorylation. 27010859 7 29 theme acyltransferase-1 1053:1069 arg1 expression 1018:1027 expression 1018:1027 expression of glycerol-3-phosphate acyltransferase-1 (GPAT1), a lipid metabolic enzyme producing lysophosphatidic acid (LPA) 1018:1141 In addition, hypoxia regulated several lipid metabolic enzymes, whereas glucosamine increased expression of glycerol-3-phosphate acyltransferase-1 (GPAT1), a lipid metabolic enzyme producing lysophosphatidic acid (LPA). 27010859 12 30 theme flap 1833:1836 arg1 necrosis 1838:1845 flap necrosis 1833:1845 flap necrosis in mouse skin flap model 1833:1870 Furthermore, transplantation of non-targeting siRNA and glucosamine-treated mESCs increased cell survival and inhibited flap necrosis in mouse skin flap model. 27010859 2 31 theme cellular 443:450 arg1 metabolism 452:461 cellular metabolism 443:461 cellular metabolism 443:461 Hypoxia activates O-linked β-N-acetyl glucosaminylation (O-GlcNAcylation) of stem cells, which contributes to regulation of cellular metabolism, as well as cell fate. 27010859 0 32 theme Glycerol-3-phosphate 0:19 arg1 upregulation 39:50 Glycerol-3-phosphate acyltransferase-1 upregulation 0:50 Glycerol-3-phosphate acyltransferase-1 upregulation by O-GlcNAcylation of Sp1 0:76 Glycerol-3-phosphate acyltransferase-1 upregulation by O-GlcNAcylation of Sp1 protects against hypoxia-induced mouse embryonic stem cell apoptosis via mTOR activation. 27010859 1 33 theme therapy 310:316 arg1 efficiency 286:295 the efficiency 282:295 the efficiency of stem cell therapy 282:316 Oxygen signaling is critical for stem cell regulation, and oxidative stress-induced stem cell apoptosis decreases the efficiency of stem cell therapy. 27010859 12 34 theme cell 1805:1808 arg1 survival 1810:1817 cell survival 1805:1817 cell survival 1805:1817 Furthermore, transplantation of non-targeting siRNA and glucosamine-treated mESCs increased cell survival and inhibited flap necrosis in mouse skin flap model. 27010859 2 35 theme cell 475:478 arg1 fate 480:483 cell fate 475:483 cell fate 475:483 Hypoxia activates O-linked β-N-acetyl glucosaminylation (O-GlcNAcylation) of stem cells, which contributes to regulation of cellular metabolism, as well as cell fate. 27010859 11 36 theme mTOR 1600:1603 arg1 inactivation 1605:1616 mTOR inactivation 1600:1616 mTOR inactivation by rapamycin (mTOR inhibitor) 1600:1646 Moreover, mTOR inactivation by rapamycin (mTOR inhibitor) increased pro-apoptotic proteins expressions and mESC apoptosis. 27010859 14 37 theme enhancing 1966:1974 arg1 O-GlcNAcylation 1976:1990 enhancing O-GlcNAcylation 1966:1990 enhancing O-GlcNAcylation of Sp1 by glucosamine 1966:2012 In conclusion, enhancing O-GlcNAcylation of Sp1 by glucosamine stimulates GPAT1 expression, which leads to inhibition of hypoxia-induced mESC apoptosis via mTOR activation. 27010859 8 38 theme Sp1 1198:1200 arg1 O-GlcNAcylation 1179:1193 glucosamine-increased O-GlcNAcylation 1157:1193 glucosamine-increased O-GlcNAcylation of Sp1, which subsequently leads to Sp1 nuclear translocation and GPAT1 expression 1157:1276 In addition, glucosamine-increased O-GlcNAcylation of Sp1, which subsequently leads to Sp1 nuclear translocation and GPAT1 expression. 27010859 3 39 theme O-GlcNAcylation 521:535 arg1 role 513:516 the role 509:516 the role of O-GlcNAcylation via glucosamine 509:551 Our study investigated the role of O-GlcNAcylation via glucosamine in the protection of hypoxia-induced apoptosis of mouse embryonic stem cells (mESCs). 27010859 0 40 theme Sp1 74:76 arg1 upregulation 39:50 Glycerol-3-phosphate acyltransferase-1 upregulation 0:50 Glycerol-3-phosphate acyltransferase-1 upregulation by O-GlcNAcylation of Sp1 0:76 Glycerol-3-phosphate acyltransferase-1 upregulation by O-GlcNAcylation of Sp1 protects against hypoxia-induced mouse embryonic stem cell apoptosis via mTOR activation. 27010859 9 41 theme siRNA 1307:1311 arg1 transfection 1313:1324 gpat1 siRNA transfection 1301:1324 gpat1 siRNA transfection 1301:1324 Silencing of GPAT1 by gpat1 siRNA transfection reduced glucosamine-mediated anti-apoptosis in mESCs and reduced mammalian target of rapamycin (mTOR) phosphorylation. 27010859 6 42 theme O-GlcNAc 806:813 arg1 level 815:819 the O-GlcNAc level 802:819 the O-GlcNAc level 802:819 Glucosamine treatment further enhanced the O-GlcNAc level and prevented hypoxia-induced mESC apoptosis, which was suppressed by O-GlcNAc transferase inhibitors. 27010859 1 43 theme cell 257:260 arg1 apoptosis 262:270 oxidative stress-induced stem cell apoptosis 227:270 oxidative stress-induced stem cell apoptosis 227:270 Oxygen signaling is critical for stem cell regulation, and oxidative stress-induced stem cell apoptosis decreases the efficiency of stem cell therapy. 27010859 6 44 theme transferase 900:910 arg1 inhibitors 912:921 O-GlcNAc transferase inhibitors 891:921 O-GlcNAc transferase inhibitors 891:921 Glucosamine treatment further enhanced the O-GlcNAc level and prevented hypoxia-induced mESC apoptosis, which was suppressed by O-GlcNAc transferase inhibitors. 27010859 10 45 dep substrates 1561:1570 arg1 4EBP1 1582:1586 4EBP1 1582:1586 4EBP1 1582:1586 Indeed, LPA prevented mESCs from undergoing hypoxia-induced apoptosis and increased phosphorylation of mTOR and its substrates (S6K1 and 4EBP1). 27010859 10 45 dep substrates 1561:1570 arg1 S6K1 1573:1576 S6K1 1573:1576 S6K1 1573:1576 Indeed, LPA prevented mESCs from undergoing hypoxia-induced apoptosis and increased phosphorylation of mTOR and its substrates (S6K1 and 4EBP1). 27010859 10 45 dep substrates 1561:1570 arg1 substrates 1561:1570 its substrates 1557:1570 its substrates (S6K1 and 4EBP1) 1557:1587 Indeed, LPA prevented mESCs from undergoing hypoxia-induced apoptosis and increased phosphorylation of mTOR and its substrates (S6K1 and 4EBP1). 27010859 8 46 theme Sp1 1231:1233 arg1 translocation 1243:1255 Sp1 nuclear translocation 1231:1255 Sp1 nuclear translocation 1231:1255 In addition, glucosamine-increased O-GlcNAcylation of Sp1, which subsequently leads to Sp1 nuclear translocation and GPAT1 expression. 27010859 4 47 theme mESCs 657:661 arg1 apoptosis 663:671 mESCs apoptosis 657:671 mESCs apoptosis 657:671 Hypoxia increased mESCs apoptosis in a time-dependent manner. 27010859 7 48 theme metabolic 969:977 arg1 enzymes 979:985 several lipid metabolic enzymes 955:985 several lipid metabolic enzymes 955:985 In addition, hypoxia regulated several lipid metabolic enzymes, whereas glucosamine increased expression of glycerol-3-phosphate acyltransferase-1 (GPAT1), a lipid metabolic enzyme producing lysophosphatidic acid (LPA). 27010859 9 49 theme GPAT1 1292:1296 arg1 Silencing 1279:1287 Silencing 1279:1287 Silencing of GPAT1 by gpat1 siRNA transfection 1279:1324 Silencing of GPAT1 by gpat1 siRNA transfection reduced glucosamine-mediated anti-apoptosis in mESCs and reduced mammalian target of rapamycin (mTOR) phosphorylation. 27010859 3 50 theme apoptosis 590:598 arg1 protection 560:569 the protection 556:569 the protection of hypoxia-induced apoptosis of mouse embryonic stem cells (mESCs) 556:636 Our study investigated the role of O-GlcNAcylation via glucosamine in the protection of hypoxia-induced apoptosis of mouse embryonic stem cells (mESCs). 27010859 7 51 theme several 955:961 arg1 enzymes 979:985 several lipid metabolic enzymes 955:985 several lipid metabolic enzymes 955:985 In addition, hypoxia regulated several lipid metabolic enzymes, whereas glucosamine increased expression of glycerol-3-phosphate acyltransferase-1 (GPAT1), a lipid metabolic enzyme producing lysophosphatidic acid (LPA). 27010859 1 52 theme stem 300:303 arg1 therapy 310:316 stem cell therapy 300:316 stem cell therapy 300:316 Oxygen signaling is critical for stem cell regulation, and oxidative stress-induced stem cell apoptosis decreases the efficiency of stem cell therapy. 27010859 8 53 theme GPAT1 1261:1265 arg1 expression 1267:1276 GPAT1 expression 1261:1276 GPAT1 expression 1261:1276 In addition, glucosamine-increased O-GlcNAcylation of Sp1, which subsequently leads to Sp1 nuclear translocation and GPAT1 expression. 27010859 12 54 from necrosis 1838:1845 arg1 model 1866:1870 mouse skin flap model 1850:1870 mouse skin flap model 1850:1870 Furthermore, transplantation of non-targeting siRNA and glucosamine-treated mESCs increased cell survival and inhibited flap necrosis in mouse skin flap model. 27010859 2 55 theme stem 396:399 arg1 cells 401:405 stem cells 396:405 stem cells 396:405 Hypoxia activates O-linked β-N-acetyl glucosaminylation (O-GlcNAcylation) of stem cells, which contributes to regulation of cellular metabolism, as well as cell fate. 27010859 9 56 theme gpat1 1301:1305 arg1 transfection 1313:1324 gpat1 siRNA transfection 1301:1324 gpat1 siRNA transfection 1301:1324 Silencing of GPAT1 by gpat1 siRNA transfection reduced glucosamine-mediated anti-apoptosis in mESCs and reduced mammalian target of rapamycin (mTOR) phosphorylation. 27010859 1 57 theme stem 201:204 arg1 regulation 211:220 stem cell regulation 201:220 stem cell regulation 201:220 Oxygen signaling is critical for stem cell regulation, and oxidative stress-induced stem cell apoptosis decreases the efficiency of stem cell therapy. 27010859 3 58 theme stem 619:622 arg1 mESCs 631:635 mESCs 631:635 mESCs 631:635 Our study investigated the role of O-GlcNAcylation via glucosamine in the protection of hypoxia-induced apoptosis of mouse embryonic stem cells (mESCs). 27010859 3 58 theme stem 619:622 arg1 cells 624:628 mouse embryonic stem cells 603:628 mouse embryonic stem cells (mESCs) 603:636 Our study investigated the role of O-GlcNAcylation via glucosamine in the protection of hypoxia-induced apoptosis of mouse embryonic stem cells (mESCs). 27010859 11 59 theme mESC 1697:1700 arg1 apoptosis 1702:1710 mESC apoptosis 1697:1710 mESC apoptosis 1697:1710 Moreover, mTOR inactivation by rapamycin (mTOR inhibitor) increased pro-apoptotic proteins expressions and mESC apoptosis. 27010859 5 60 theme O-GlcNAc 747:754 arg1 level 756:760 the O-GlcNAc level 743:760 the O-GlcNAc level 743:760 Moreover, hypoxia also slightly increased the O-GlcNAc level. 27010859 6 61 theme hypoxia-induced 835:849 arg1 apoptosis 856:864 hypoxia-induced mESC apoptosis 835:864 hypoxia-induced mESC apoptosis 835:864 Glucosamine treatment further enhanced the O-GlcNAc level and prevented hypoxia-induced mESC apoptosis, which was suppressed by O-GlcNAc transferase inhibitors. 27010859 2 62 theme β-N-acetyl 346:355 arg1 O-GlcNAcylation 376:390 O-GlcNAcylation 376:390 O-GlcNAcylation 376:390 Hypoxia activates O-linked β-N-acetyl glucosaminylation (O-GlcNAcylation) of stem cells, which contributes to regulation of cellular metabolism, as well as cell fate. 27010859 2 62 theme β-N-acetyl 346:355 arg1 glucosaminylation 357:373 O-linked β-N-acetyl glucosaminylation 337:373 O-linked β-N-acetyl glucosaminylation (O-GlcNAcylation) 337:391 Hypoxia activates O-linked β-N-acetyl glucosaminylation (O-GlcNAcylation) of stem cells, which contributes to regulation of cellular metabolism, as well as cell fate. 27010859 14 63 theme mESC 2088:2091 arg1 apoptosis 2093:2101 hypoxia-induced mESC apoptosis 2072:2101 hypoxia-induced mESC apoptosis 2072:2101 In conclusion, enhancing O-GlcNAcylation of Sp1 by glucosamine stimulates GPAT1 expression, which leads to inhibition of hypoxia-induced mESC apoptosis via mTOR activation. 27010859 12 64 theme mESCs 1789:1793 arg1 transplantation 1726:1740 transplantation 1726:1740 transplantation of non-targeting siRNA and glucosamine-treated mESCs 1726:1793 Furthermore, transplantation of non-targeting siRNA and glucosamine-treated mESCs increased cell survival and inhibited flap necrosis in mouse skin flap model. 27010859 1 65 theme stress-induced 237:250 arg1 apoptosis 262:270 oxidative stress-induced stem cell apoptosis 227:270 oxidative stress-induced stem cell apoptosis 227:270 Oxygen signaling is critical for stem cell regulation, and oxidative stress-induced stem cell apoptosis decreases the efficiency of stem cell therapy. 27010859 4 66 theme time-dependent 678:691 arg1 manner 693:698 a time-dependent manner 676:698 a time-dependent manner 676:698 Hypoxia increased mESCs apoptosis in a time-dependent manner. 27010859 13 67 theme expression 1904:1913 arg1 silencing 1885:1893 silencing 1885:1893 silencing of GPAT1 expression 1885:1913 Conversely, silencing of GPAT1 expression reversed those glucosamine effects. 27010859 2 68 link O-linked 337:344 arg1 O-GlcNAcylation 376:390 O-GlcNAcylation 376:390 O-GlcNAcylation 376:390 Hypoxia activates O-linked β-N-acetyl glucosaminylation (O-GlcNAcylation) of stem cells, which contributes to regulation of cellular metabolism, as well as cell fate. 27010859 2 68 link O-linked 337:344 arg1 glucosaminylation 357:373 O-linked β-N-acetyl glucosaminylation 337:373 O-linked β-N-acetyl glucosaminylation (O-GlcNAcylation) 337:391 Hypoxia activates O-linked β-N-acetyl glucosaminylation (O-GlcNAcylation) of stem cells, which contributes to regulation of cellular metabolism, as well as cell fate. 27010859 12 69 theme non-targeting 1745:1757 arg1 siRNA 1759:1763 non-targeting siRNA 1745:1763 non-targeting siRNA 1745:1763 Furthermore, transplantation of non-targeting siRNA and glucosamine-treated mESCs increased cell survival and inhibited flap necrosis in mouse skin flap model. 27010859 9 70 theme glucosamine-mediated 1334:1353 arg1 anti-apoptosis 1355:1368 glucosamine-mediated anti-apoptosis 1334:1368 glucosamine-mediated anti-apoptosis in mESCs 1334:1377 Silencing of GPAT1 by gpat1 siRNA transfection reduced glucosamine-mediated anti-apoptosis in mESCs and reduced mammalian target of rapamycin (mTOR) phosphorylation. 27010859 9 71 theme mammalian 1391:1399 arg1 target 1401:1406 mammalian target 1391:1406 mammalian target of rapamycin (mTOR) phosphorylation 1391:1442 Silencing of GPAT1 by gpat1 siRNA transfection reduced glucosamine-mediated anti-apoptosis in mESCs and reduced mammalian target of rapamycin (mTOR) phosphorylation. 27010859 3 72 theme mouse 603:607 arg1 mESCs 631:635 mESCs 631:635 mESCs 631:635 Our study investigated the role of O-GlcNAcylation via glucosamine in the protection of hypoxia-induced apoptosis of mouse embryonic stem cells (mESCs). 27010859 3 72 theme mouse 603:607 arg1 cells 624:628 mouse embryonic stem cells 603:628 mouse embryonic stem cells (mESCs) 603:636 Our study investigated the role of O-GlcNAcylation via glucosamine in the protection of hypoxia-induced apoptosis of mouse embryonic stem cells (mESCs). 27010859 0 73 theme hypoxia-induced 95:109 arg1 apoptosis 137:145 hypoxia-induced mouse embryonic stem cell apoptosis 95:145 hypoxia-induced mouse embryonic stem cell apoptosis 95:145 Glycerol-3-phosphate acyltransferase-1 upregulation by O-GlcNAcylation of Sp1 protects against hypoxia-induced mouse embryonic stem cell apoptosis via mTOR activation. 27010859 12 74 theme flap 1861:1864 arg1 model 1866:1870 mouse skin flap model 1850:1870 mouse skin flap model 1850:1870 Furthermore, transplantation of non-targeting siRNA and glucosamine-treated mESCs increased cell survival and inhibited flap necrosis in mouse skin flap model. 27010859 7 75 theme metabolic 1088:1096 arg1 acyltransferase-1 1053:1069 glycerol-3-phosphate acyltransferase-1 1032:1069 glycerol-3-phosphate acyltransferase-1 (GPAT1) 1032:1077 In addition, hypoxia regulated several lipid metabolic enzymes, whereas glucosamine increased expression of glycerol-3-phosphate acyltransferase-1 (GPAT1), a lipid metabolic enzyme producing lysophosphatidic acid (LPA). 27010859 7 75 theme metabolic 1088:1096 arg1 enzyme 1098:1103 a lipid metabolic enzyme 1080:1103 a lipid metabolic enzyme producing lysophosphatidic acid (LPA) 1080:1141 In addition, hypoxia regulated several lipid metabolic enzymes, whereas glucosamine increased expression of glycerol-3-phosphate acyltransferase-1 (GPAT1), a lipid metabolic enzyme producing lysophosphatidic acid (LPA). 27010859 0 76 theme embryonic 117:125 arg1 apoptosis 137:145 hypoxia-induced mouse embryonic stem cell apoptosis 95:145 hypoxia-induced mouse embryonic stem cell apoptosis 95:145 Glycerol-3-phosphate acyltransferase-1 upregulation by O-GlcNAcylation of Sp1 protects against hypoxia-induced mouse embryonic stem cell apoptosis via mTOR activation. 27010859 12 77 theme mouse 1850:1854 arg1 model 1866:1870 mouse skin flap model 1850:1870 mouse skin flap model 1850:1870 Furthermore, transplantation of non-targeting siRNA and glucosamine-treated mESCs increased cell survival and inhibited flap necrosis in mouse skin flap model. 27010859 11 78 theme mTOR 1632:1635 arg1 rapamycin 1621:1629 rapamycin 1621:1629 rapamycin (mTOR inhibitor) 1621:1646 Moreover, mTOR inactivation by rapamycin (mTOR inhibitor) increased pro-apoptotic proteins expressions and mESC apoptosis. 27010859 11 78 theme mTOR 1632:1635 arg1 inhibitor 1637:1645 mTOR inhibitor 1632:1645 mTOR inhibitor 1632:1645 Moreover, mTOR inactivation by rapamycin (mTOR inhibitor) increased pro-apoptotic proteins expressions and mESC apoptosis. 27010859 0 79 theme cell 132:135 arg1 apoptosis 137:145 hypoxia-induced mouse embryonic stem cell apoptosis 95:145 hypoxia-induced mouse embryonic stem cell apoptosis 95:145 Glycerol-3-phosphate acyltransferase-1 upregulation by O-GlcNAcylation of Sp1 protects against hypoxia-induced mouse embryonic stem cell apoptosis via mTOR activation. 27010859 2 80 theme O-linked 337:344 arg1 O-GlcNAcylation 376:390 O-GlcNAcylation 376:390 O-GlcNAcylation 376:390 Hypoxia activates O-linked β-N-acetyl glucosaminylation (O-GlcNAcylation) of stem cells, which contributes to regulation of cellular metabolism, as well as cell fate. 27010859 2 80 theme O-linked 337:344 arg1 glucosaminylation 357:373 O-linked β-N-acetyl glucosaminylation 337:373 O-linked β-N-acetyl glucosaminylation (O-GlcNAcylation) 337:391 Hypoxia activates O-linked β-N-acetyl glucosaminylation (O-GlcNAcylation) of stem cells, which contributes to regulation of cellular metabolism, as well as cell fate. 27010859 6 81 theme Glucosamine 763:773 arg1 treatment 775:783 Glucosamine treatment 763:783 Glucosamine treatment 763:783 Glucosamine treatment further enhanced the O-GlcNAc level and prevented hypoxia-induced mESC apoptosis, which was suppressed by O-GlcNAc transferase inhibitors. 27010859 0 82 theme acyltransferase-1 21:37 arg1 upregulation 39:50 Glycerol-3-phosphate acyltransferase-1 upregulation 0:50 Glycerol-3-phosphate acyltransferase-1 upregulation by O-GlcNAcylation of Sp1 0:76 Glycerol-3-phosphate acyltransferase-1 upregulation by O-GlcNAcylation of Sp1 protects against hypoxia-induced mouse embryonic stem cell apoptosis via mTOR activation. 27010859 14 83 theme mTOR 2107:2110 arg1 activation 2112:2121 mTOR activation 2107:2121 mTOR activation 2107:2121 In conclusion, enhancing O-GlcNAcylation of Sp1 by glucosamine stimulates GPAT1 expression, which leads to inhibition of hypoxia-induced mESC apoptosis via mTOR activation. 27010859 8 84 theme glucosamine-increased 1157:1177 arg1 O-GlcNAcylation 1179:1193 glucosamine-increased O-GlcNAcylation 1157:1193 glucosamine-increased O-GlcNAcylation of Sp1, which subsequently leads to Sp1 nuclear translocation and GPAT1 expression 1157:1276 In addition, glucosamine-increased O-GlcNAcylation of Sp1, which subsequently leads to Sp1 nuclear translocation and GPAT1 expression. 27010859 7 85 theme glycerol-3-phosphate 1032:1051 arg1 GPAT1 1072:1076 GPAT1 1072:1076 GPAT1 1072:1076 In addition, hypoxia regulated several lipid metabolic enzymes, whereas glucosamine increased expression of glycerol-3-phosphate acyltransferase-1 (GPAT1), a lipid metabolic enzyme producing lysophosphatidic acid (LPA). 27010859 7 85 theme glycerol-3-phosphate 1032:1051 arg1 enzyme 1098:1103 a lipid metabolic enzyme 1080:1103 a lipid metabolic enzyme producing lysophosphatidic acid (LPA) 1080:1141 In addition, hypoxia regulated several lipid metabolic enzymes, whereas glucosamine increased expression of glycerol-3-phosphate acyltransferase-1 (GPAT1), a lipid metabolic enzyme producing lysophosphatidic acid (LPA). 27010859 7 85 theme glycerol-3-phosphate 1032:1051 arg1 acyltransferase-1 1053:1069 glycerol-3-phosphate acyltransferase-1 1032:1069 glycerol-3-phosphate acyltransferase-1 (GPAT1) 1032:1077 In addition, hypoxia regulated several lipid metabolic enzymes, whereas glucosamine increased expression of glycerol-3-phosphate acyltransferase-1 (GPAT1), a lipid metabolic enzyme producing lysophosphatidic acid (LPA). 27010859 2 86 theme fate 480:483 arg1 regulation 429:438 regulation 429:438 regulation of cellular metabolism, as well as cell fate 429:483 Hypoxia activates O-linked β-N-acetyl glucosaminylation (O-GlcNAcylation) of stem cells, which contributes to regulation of cellular metabolism, as well as cell fate. 27010859 14 87 theme Sp1 1995:1997 arg1 O-GlcNAcylation 1976:1990 enhancing O-GlcNAcylation 1966:1990 enhancing O-GlcNAcylation of Sp1 by glucosamine 1966:2012 In conclusion, enhancing O-GlcNAcylation of Sp1 by glucosamine stimulates GPAT1 expression, which leads to inhibition of hypoxia-induced mESC apoptosis via mTOR activation. 27010859 2 88 theme metabolism 452:461 arg1 regulation 429:438 regulation 429:438 regulation of cellular metabolism, as well as cell fate 429:483 Hypoxia activates O-linked β-N-acetyl glucosaminylation (O-GlcNAcylation) of stem cells, which contributes to regulation of cellular metabolism, as well as cell fate. 27010859 8 89 theme nuclear 1235:1241 arg1 translocation 1243:1255 Sp1 nuclear translocation 1231:1255 Sp1 nuclear translocation 1231:1255 In addition, glucosamine-increased O-GlcNAcylation of Sp1, which subsequently leads to Sp1 nuclear translocation and GPAT1 expression. 27010859 6 90 theme O-GlcNAc 891:898 arg1 transferase 900:910 O-GlcNAc transferase 891:910 O-GlcNAc transferase inhibitors 891:921 Glucosamine treatment further enhanced the O-GlcNAc level and prevented hypoxia-induced mESC apoptosis, which was suppressed by O-GlcNAc transferase inhibitors. 27010859 10 91 theme hypoxia-induced 1489:1503 arg1 apoptosis 1505:1513 hypoxia-induced apoptosis 1489:1513 hypoxia-induced apoptosis 1489:1513 Indeed, LPA prevented mESCs from undergoing hypoxia-induced apoptosis and increased phosphorylation of mTOR and its substrates (S6K1 and 4EBP1). 27010859 7 92 theme lipid 963:967 arg1 enzymes 979:985 several lipid metabolic enzymes 955:985 several lipid metabolic enzymes 955:985 In addition, hypoxia regulated several lipid metabolic enzymes, whereas glucosamine increased expression of glycerol-3-phosphate acyltransferase-1 (GPAT1), a lipid metabolic enzyme producing lysophosphatidic acid (LPA). 26714046 5 0 theme GALNT3 646:651 arg1 level 658:662 The GALNT3 mRNA level 642:662 The GALNT3 mRNA level 642:662 METHODS AND RESULTS The GALNT3 mRNA level was decreased by 48.2% in CAD patients (n = 58), compared with that of controls (n = 120). 26714046 9 1 theme expression 1356:1365 arg1 ratio 1317:1321 the ratio 1313:1321 the ratio of cytosolic p-p38 MAPK/p38 MAPK expression 1313:1365 Finally, the ratio of cytosolic p-p38 MAPK/p38 MAPK expression was significantly increased with GALNT3 knockdown and lower with GALNT3 overexpression, while the p38 MAPK inhibitor SB203580 blocked the effects of GALNT3 knockdown. 26714046 8 2 theme GALNT3 1084:1089 arg1 overexpression 1066:1079 overexpression 1066:1079 overexpression of GALNT3 1066:1089 Conversely, overexpression of GALNT3 significantly inhibited HUVECs apoptosis and down-regulated the expression of MMP-2 and MMP-14 genes, in addition, overexpression of GALNT3 attenuated hypoxia-induced apoptosis and expression of MMP-2 and MMP-14. 26714046 4 3 theme GALNT3 587:592 arg1 gene 594:597 GALNT3 gene 587:597 GALNT3 gene 587:597 The present study investigated the function and mechanisms of GALNT3 gene in endothelial injury. 26714046 10 4 theme MMP-2 1719:1723 arg1 expression 1705:1714 the expression 1701:1714 the expression of MMP-2 and MMP-14 genes 1701:1740 CONCLUSIONS Expression of GALNT3 was reduced in CAD patients, and down regulation of GALNT3 contributed to endothelial injury by promoting apoptosis and up-regulating the expression of MMP-2 and MMP-14 genes via p38 MAPK activation. 26714046 6 5 theme vein 814:817 arg1 HUVECs 838:843 HUVECs 838:843 HUVECs 838:843 Expression of GALNT3 was also decreased in human umbilical vein endothelial cells (HUVECs) treated with CAD sera and subjected to hypoxia in vitro. 26714046 6 5 theme vein 814:817 arg1 cells 831:835 human umbilical vein endothelial cells 798:835 human umbilical vein endothelial cells (HUVECs) treated with CAD sera and subjected to hypoxia in vitro 798:900 Expression of GALNT3 was also decreased in human umbilical vein endothelial cells (HUVECs) treated with CAD sera and subjected to hypoxia in vitro. 26714046 8 6 theme MMP-14 1179:1184 arg1 genes 1186:1190 MMP-14 genes 1179:1190 MMP-14 genes 1179:1190 Conversely, overexpression of GALNT3 significantly inhibited HUVECs apoptosis and down-regulated the expression of MMP-2 and MMP-14 genes, in addition, overexpression of GALNT3 attenuated hypoxia-induced apoptosis and expression of MMP-2 and MMP-14. 26714046 7 7 theme matrix 1016:1021 arg1 MMP-14 1045:1050 MMP-14 1045:1050 MMP-14 1045:1050 Knockdown of GALNT3 promoted apoptosis and up-regulated the expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-14 (MMP-14). 26714046 7 7 theme matrix 1016:1021 arg1 metalloproteinase-14 1023:1042 matrix metalloproteinase-14 1016:1042 matrix metalloproteinase-14 (MMP-14) 1016:1051 Knockdown of GALNT3 promoted apoptosis and up-regulated the expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-14 (MMP-14). 26714046 5 8 theme = 747:747 arg1 controls 735:742 controls 735:742 controls (n = 120) 735:752 METHODS AND RESULTS The GALNT3 mRNA level was decreased by 48.2% in CAD patients (n = 58), compared with that of controls (n = 120). 26714046 5 8 theme = 747:747 arg1 n 745:745 n = 120 745:751 n = 120 745:751 METHODS AND RESULTS The GALNT3 mRNA level was decreased by 48.2% in CAD patients (n = 58), compared with that of controls (n = 120). 26714046 6 9 theme human 798:802 arg1 HUVECs 838:843 HUVECs 838:843 HUVECs 838:843 Expression of GALNT3 was also decreased in human umbilical vein endothelial cells (HUVECs) treated with CAD sera and subjected to hypoxia in vitro. 26714046 6 9 theme human 798:802 arg1 cells 831:835 human umbilical vein endothelial cells 798:835 human umbilical vein endothelial cells (HUVECs) treated with CAD sera and subjected to hypoxia in vitro 798:900 Expression of GALNT3 was also decreased in human umbilical vein endothelial cells (HUVECs) treated with CAD sera and subjected to hypoxia in vitro. 26714046 10 10 theme GALNT3 1560:1565 arg1 Expression 1546:1555 CONCLUSIONS Expression 1534:1555 CONCLUSIONS Expression of GALNT3 1534:1565 CONCLUSIONS Expression of GALNT3 was reduced in CAD patients, and down regulation of GALNT3 contributed to endothelial injury by promoting apoptosis and up-regulating the expression of MMP-2 and MMP-14 genes via p38 MAPK activation. 26714046 3 11 from effect 489:494 arg1 CAD 509:511 CAD 509:511 CAD 509:511 However the effect of GALNT3 in CAD is unknown. 26714046 1 12 from N-acetylgalactosamine 259:279 arg1 step 348:351 the first step 338:351 the first step of O-linked oligosaccharide biosynthesis 338:392 OBJECTIVE The GALNT3 gene encodes polypeptide N-acetylgalactosaminyl transferase 3 (GalNAc-T3), a member of the GalNAc-Ts family that transfers the N-acetylgalactosamine to the hydroxyl group of serine and threonine residue in the first step of O-linked oligosaccharide biosynthesis. 26714046 1 13 theme biosynthesis 381:392 arg1 step 348:351 the first step 338:351 the first step of O-linked oligosaccharide biosynthesis 338:392 OBJECTIVE The GALNT3 gene encodes polypeptide N-acetylgalactosaminyl transferase 3 (GalNAc-T3), a member of the GalNAc-Ts family that transfers the N-acetylgalactosamine to the hydroxyl group of serine and threonine residue in the first step of O-linked oligosaccharide biosynthesis. 26714046 10 14 theme MMP-14 1729:1734 arg1 genes 1736:1740 MMP-14 genes 1729:1740 MMP-14 genes 1729:1740 CONCLUSIONS Expression of GALNT3 was reduced in CAD patients, and down regulation of GALNT3 contributed to endothelial injury by promoting apoptosis and up-regulating the expression of MMP-2 and MMP-14 genes via p38 MAPK activation. 26714046 10 15 theme CAD 1582:1584 arg1 patients 1586:1593 CAD patients 1582:1593 CAD patients 1582:1593 CONCLUSIONS Expression of GALNT3 was reduced in CAD patients, and down regulation of GALNT3 contributed to endothelial injury by promoting apoptosis and up-regulating the expression of MMP-2 and MMP-14 genes via p38 MAPK activation. 26714046 7 16 theme matrix 977:982 arg1 MMP-2 1005:1009 MMP-2 1005:1009 MMP-2 1005:1009 Knockdown of GALNT3 promoted apoptosis and up-regulated the expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-14 (MMP-14). 26714046 7 16 theme matrix 977:982 arg1 metalloproteinase-2 984:1002 matrix metalloproteinase-2 977:1002 matrix metalloproteinase-2 (MMP-2) 977:1010 Knockdown of GALNT3 promoted apoptosis and up-regulated the expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-14 (MMP-14). 26714046 9 17 theme GALNT3 1432:1437 arg1 overexpression 1439:1452 GALNT3 overexpression 1432:1452 GALNT3 overexpression 1432:1452 Finally, the ratio of cytosolic p-p38 MAPK/p38 MAPK expression was significantly increased with GALNT3 knockdown and lower with GALNT3 overexpression, while the p38 MAPK inhibitor SB203580 blocked the effects of GALNT3 knockdown. 26714046 8 18 theme MMP-2 1169:1173 arg1 expression 1155:1164 the expression 1151:1164 the expression of MMP-2 and MMP-14 genes 1151:1190 Conversely, overexpression of GALNT3 significantly inhibited HUVECs apoptosis and down-regulated the expression of MMP-2 and MMP-14 genes, in addition, overexpression of GALNT3 attenuated hypoxia-induced apoptosis and expression of MMP-2 and MMP-14. 26714046 6 19 theme CAD 859:861 arg1 sera 863:866 CAD sera 859:866 CAD sera 859:866 Expression of GALNT3 was also decreased in human umbilical vein endothelial cells (HUVECs) treated with CAD sera and subjected to hypoxia in vitro. 26714046 8 20 theme GALNT3 1224:1229 arg1 overexpression 1206:1219 overexpression 1206:1219 overexpression of GALNT3 1206:1229 Conversely, overexpression of GALNT3 significantly inhibited HUVECs apoptosis and down-regulated the expression of MMP-2 and MMP-14 genes, in addition, overexpression of GALNT3 attenuated hypoxia-induced apoptosis and expression of MMP-2 and MMP-14. 26714046 10 21 theme MAPK 1750:1753 arg1 activation 1755:1764 p38 MAPK activation 1746:1764 p38 MAPK activation 1746:1764 CONCLUSIONS Expression of GALNT3 was reduced in CAD patients, and down regulation of GALNT3 contributed to endothelial injury by promoting apoptosis and up-regulating the expression of MMP-2 and MMP-14 genes via p38 MAPK activation. 26714046 7 22 theme metalloproteinase-14 1023:1042 arg1 expression 963:972 the expression 959:972 the expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-14 (MMP-14) 959:1051 Knockdown of GALNT3 promoted apoptosis and up-regulated the expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-14 (MMP-14). 26714046 8 23 theme hypoxia-induced 1242:1256 arg1 apoptosis 1258:1266 hypoxia-induced apoptosis 1242:1266 hypoxia-induced apoptosis 1242:1266 Conversely, overexpression of GALNT3 significantly inhibited HUVECs apoptosis and down-regulated the expression of MMP-2 and MMP-14 genes, in addition, overexpression of GALNT3 attenuated hypoxia-induced apoptosis and expression of MMP-2 and MMP-14. 26714046 1 24 theme GALNT3 125:130 arg1 transferase 180:190 polypeptide N-acetylgalactosaminyl transferase 3 145:192 polypeptide N-acetylgalactosaminyl transferase 3 (GalNAc-T3) 145:204 OBJECTIVE The GALNT3 gene encodes polypeptide N-acetylgalactosaminyl transferase 3 (GalNAc-T3), a member of the GalNAc-Ts family that transfers the N-acetylgalactosamine to the hydroxyl group of serine and threonine residue in the first step of O-linked oligosaccharide biosynthesis. 26714046 1 24 theme GALNT3 125:130 arg1 gene 132:135 The GALNT3 gene 121:135 The GALNT3 gene 121:135 OBJECTIVE The GALNT3 gene encodes polypeptide N-acetylgalactosaminyl transferase 3 (GalNAc-T3), a member of the GalNAc-Ts family that transfers the N-acetylgalactosamine to the hydroxyl group of serine and threonine residue in the first step of O-linked oligosaccharide biosynthesis. 26714046 9 25 theme MAPK 1469:1472 arg1 SB203580 1484:1491 the p38 MAPK inhibitor SB203580 1461:1491 the p38 MAPK inhibitor SB203580 1461:1491 Finally, the ratio of cytosolic p-p38 MAPK/p38 MAPK expression was significantly increased with GALNT3 knockdown and lower with GALNT3 overexpression, while the p38 MAPK inhibitor SB203580 blocked the effects of GALNT3 knockdown. 26714046 1 26 theme N-acetylgalactosaminyl 157:178 arg1 transferase 180:190 polypeptide N-acetylgalactosaminyl transferase 3 145:192 polypeptide N-acetylgalactosaminyl transferase 3 (GalNAc-T3) 145:204 OBJECTIVE The GALNT3 gene encodes polypeptide N-acetylgalactosaminyl transferase 3 (GalNAc-T3), a member of the GalNAc-Ts family that transfers the N-acetylgalactosamine to the hydroxyl group of serine and threonine residue in the first step of O-linked oligosaccharide biosynthesis. 26714046 1 26 theme N-acetylgalactosaminyl 157:178 arg1 GalNAc-T3 195:203 GalNAc-T3 195:203 GalNAc-T3 195:203 OBJECTIVE The GALNT3 gene encodes polypeptide N-acetylgalactosaminyl transferase 3 (GalNAc-T3), a member of the GalNAc-Ts family that transfers the N-acetylgalactosamine to the hydroxyl group of serine and threonine residue in the first step of O-linked oligosaccharide biosynthesis. 26714046 1 26 theme N-acetylgalactosaminyl 157:178 arg1 gene 132:135 The GALNT3 gene 121:135 The GALNT3 gene 121:135 OBJECTIVE The GALNT3 gene encodes polypeptide N-acetylgalactosaminyl transferase 3 (GalNAc-T3), a member of the GalNAc-Ts family that transfers the N-acetylgalactosamine to the hydroxyl group of serine and threonine residue in the first step of O-linked oligosaccharide biosynthesis. 26714046 1 26 theme N-acetylgalactosaminyl 157:178 arg1 member 209:214 a member 207:214 a member of the GalNAc-Ts family that transfers the N-acetylgalactosamine to the hydroxyl group of serine and threonine residue in the first step of O-linked oligosaccharide biosynthesis 207:392 OBJECTIVE The GALNT3 gene encodes polypeptide N-acetylgalactosaminyl transferase 3 (GalNAc-T3), a member of the GalNAc-Ts family that transfers the N-acetylgalactosamine to the hydroxyl group of serine and threonine residue in the first step of O-linked oligosaccharide biosynthesis. 26714046 0 27 theme p38 83:85 arg1 pathway 102:108 p38 MAPK signaling pathway 83:108 p38 MAPK signaling pathway 83:108 Down regulation of GALNT3 contributes to endothelial cell injury via activation of p38 MAPK signaling pathway. 26714046 4 28 dep function 560:567 arg1 the 556:558 the 556:558 the 556:558 The present study investigated the function and mechanisms of GALNT3 gene in endothelial injury. 26714046 0 29 theme signaling 92:100 arg1 pathway 102:108 p38 MAPK signaling pathway 83:108 p38 MAPK signaling pathway 83:108 Down regulation of GALNT3 contributes to endothelial cell injury via activation of p38 MAPK signaling pathway. 26714046 1 30 theme O-linked 356:363 arg1 biosynthesis 381:392 O-linked oligosaccharide biosynthesis 356:392 O-linked oligosaccharide biosynthesis 356:392 OBJECTIVE The GALNT3 gene encodes polypeptide N-acetylgalactosaminyl transferase 3 (GalNAc-T3), a member of the GalNAc-Ts family that transfers the N-acetylgalactosamine to the hydroxyl group of serine and threonine residue in the first step of O-linked oligosaccharide biosynthesis. 26714046 1 31 dep serine 306:311 arg1 residue 327:333 residue 327:333 residue 327:333 OBJECTIVE The GALNT3 gene encodes polypeptide N-acetylgalactosaminyl transferase 3 (GalNAc-T3), a member of the GalNAc-Ts family that transfers the N-acetylgalactosamine to the hydroxyl group of serine and threonine residue in the first step of O-linked oligosaccharide biosynthesis. 26714046 0 32 theme Down 0:3 arg1 regulation 5:14 Down regulation 0:14 Down regulation of GALNT3 0:24 Down regulation of GALNT3 contributes to endothelial cell injury via activation of p38 MAPK signaling pathway. 26714046 9 33 theme knockdown 1523:1531 arg1 effects 1505:1511 the effects 1501:1511 the effects of GALNT3 knockdown 1501:1531 Finally, the ratio of cytosolic p-p38 MAPK/p38 MAPK expression was significantly increased with GALNT3 knockdown and lower with GALNT3 overexpression, while the p38 MAPK inhibitor SB203580 blocked the effects of GALNT3 knockdown. 26714046 2 34 theme coronary 446:453 arg1 CAD 471:473 CAD 471:473 CAD 471:473 Emerging evidences have linked GalNAc-Ts family to coronary artery disease (CAD). 26714046 2 34 theme coronary 446:453 arg1 disease 462:468 coronary artery disease 446:468 coronary artery disease (CAD) 446:474 Emerging evidences have linked GalNAc-Ts family to coronary artery disease (CAD). 26714046 1 35 theme hydroxyl 288:295 arg1 serine 306:311 serine 306:311 serine 306:311 OBJECTIVE The GALNT3 gene encodes polypeptide N-acetylgalactosaminyl transferase 3 (GalNAc-T3), a member of the GalNAc-Ts family that transfers the N-acetylgalactosamine to the hydroxyl group of serine and threonine residue in the first step of O-linked oligosaccharide biosynthesis. 26714046 1 35 theme hydroxyl 288:295 arg1 group 297:301 the hydroxyl group 284:301 the hydroxyl group of serine and threonine residue 284:333 OBJECTIVE The GALNT3 gene encodes polypeptide N-acetylgalactosaminyl transferase 3 (GalNAc-T3), a member of the GalNAc-Ts family that transfers the N-acetylgalactosamine to the hydroxyl group of serine and threonine residue in the first step of O-linked oligosaccharide biosynthesis. 26714046 1 35 theme hydroxyl 288:295 arg1 threonine 317:325 threonine 317:325 threonine 317:325 OBJECTIVE The GALNT3 gene encodes polypeptide N-acetylgalactosaminyl transferase 3 (GalNAc-T3), a member of the GalNAc-Ts family that transfers the N-acetylgalactosamine to the hydroxyl group of serine and threonine residue in the first step of O-linked oligosaccharide biosynthesis. 26714046 10 36 theme GALNT3 1619:1624 arg1 regulation 1605:1614 down regulation 1600:1614 down regulation of GALNT3 1600:1624 CONCLUSIONS Expression of GALNT3 was reduced in CAD patients, and down regulation of GALNT3 contributed to endothelial injury by promoting apoptosis and up-regulating the expression of MMP-2 and MMP-14 genes via p38 MAPK activation. 26714046 11 37 theme future 1804:1809 arg1 intervention 1823:1834 future therapeutic intervention 1804:1834 future therapeutic intervention for CAD 1804:1842 GALNT3 may be a potential target for future therapeutic intervention for CAD. 26714046 0 38 theme endothelial 41:51 arg1 injury 58:63 endothelial cell injury 41:63 endothelial cell injury 41:63 Down regulation of GALNT3 contributes to endothelial cell injury via activation of p38 MAPK signaling pathway. 26714046 6 39 theme GALNT3 769:774 arg1 Expression 755:764 Expression 755:764 Expression of GALNT3 755:774 Expression of GALNT3 was also decreased in human umbilical vein endothelial cells (HUVECs) treated with CAD sera and subjected to hypoxia in vitro. 26714046 4 40 from mechanisms 573:582 arg1 injury 614:619 endothelial injury 602:619 endothelial injury 602:619 The present study investigated the function and mechanisms of GALNT3 gene in endothelial injury. 26714046 4 41 theme gene 594:597 arg1 mechanisms 573:582 mechanisms 573:582 mechanisms 573:582 The present study investigated the function and mechanisms of GALNT3 gene in endothelial injury. 26714046 4 41 theme gene 594:597 arg1 function 560:567 function 560:567 function 560:567 The present study investigated the function and mechanisms of GALNT3 gene in endothelial injury. 26714046 1 42 theme GalNAc-Ts 223:231 arg1 family 233:238 the GalNAc-Ts family 219:238 the GalNAc-Ts family 219:238 OBJECTIVE The GALNT3 gene encodes polypeptide N-acetylgalactosaminyl transferase 3 (GalNAc-T3), a member of the GalNAc-Ts family that transfers the N-acetylgalactosamine to the hydroxyl group of serine and threonine residue in the first step of O-linked oligosaccharide biosynthesis. 26714046 4 43 theme endothelial 602:612 arg1 injury 614:619 endothelial injury 602:619 endothelial injury 602:619 The present study investigated the function and mechanisms of GALNT3 gene in endothelial injury. 26714046 3 44 theme GALNT3 499:504 arg1 effect 489:494 the effect 485:494 the effect of GALNT3 in CAD 485:511 However the effect of GALNT3 in CAD is unknown. 26714046 3 44 theme GALNT3 499:504 arg1 unknown 516:522 unknown 516:522 unknown 516:522 However the effect of GALNT3 in CAD is unknown. 26714046 9 45 theme MAPK 1351:1354 arg1 expression 1356:1365 cytosolic p-p38 MAPK/p38 MAPK expression 1326:1365 cytosolic p-p38 MAPK/p38 MAPK expression 1326:1365 Finally, the ratio of cytosolic p-p38 MAPK/p38 MAPK expression was significantly increased with GALNT3 knockdown and lower with GALNT3 overexpression, while the p38 MAPK inhibitor SB203580 blocked the effects of GALNT3 knockdown. 26714046 6 46 dep cells 831:835 arg1 subjected 872:880 subjected 872:880 subjected to hypoxia in vitro 872:900 Expression of GALNT3 was also decreased in human umbilical vein endothelial cells (HUVECs) treated with CAD sera and subjected to hypoxia in vitro. 26714046 6 46 dep cells 831:835 arg1 treated 846:852 treated 846:852 treated with CAD sera 846:866 Expression of GALNT3 was also decreased in human umbilical vein endothelial cells (HUVECs) treated with CAD sera and subjected to hypoxia in vitro. 26714046 10 47 theme CONCLUSIONS 1534:1544 arg1 Expression 1546:1555 CONCLUSIONS Expression 1534:1555 CONCLUSIONS Expression of GALNT3 1534:1565 CONCLUSIONS Expression of GALNT3 was reduced in CAD patients, and down regulation of GALNT3 contributed to endothelial injury by promoting apoptosis and up-regulating the expression of MMP-2 and MMP-14 genes via p38 MAPK activation. 26714046 5 48 theme mRNA 653:656 arg1 level 658:662 The GALNT3 mRNA level 642:662 The GALNT3 mRNA level 642:662 METHODS AND RESULTS The GALNT3 mRNA level was decreased by 48.2% in CAD patients (n = 58), compared with that of controls (n = 120). 26714046 6 49 theme endothelial 819:829 arg1 HUVECs 838:843 HUVECs 838:843 HUVECs 838:843 Expression of GALNT3 was also decreased in human umbilical vein endothelial cells (HUVECs) treated with CAD sera and subjected to hypoxia in vitro. 26714046 6 49 theme endothelial 819:829 arg1 cells 831:835 human umbilical vein endothelial cells 798:835 human umbilical vein endothelial cells (HUVECs) treated with CAD sera and subjected to hypoxia in vitro 798:900 Expression of GALNT3 was also decreased in human umbilical vein endothelial cells (HUVECs) treated with CAD sera and subjected to hypoxia in vitro. 26714046 9 50 theme inhibitor 1474:1482 arg1 SB203580 1484:1491 the p38 MAPK inhibitor SB203580 1461:1491 the p38 MAPK inhibitor SB203580 1461:1491 Finally, the ratio of cytosolic p-p38 MAPK/p38 MAPK expression was significantly increased with GALNT3 knockdown and lower with GALNT3 overexpression, while the p38 MAPK inhibitor SB203580 blocked the effects of GALNT3 knockdown. 26714046 6 51 theme umbilical 804:812 arg1 HUVECs 838:843 HUVECs 838:843 HUVECs 838:843 Expression of GALNT3 was also decreased in human umbilical vein endothelial cells (HUVECs) treated with CAD sera and subjected to hypoxia in vitro. 26714046 6 51 theme umbilical 804:812 arg1 cells 831:835 human umbilical vein endothelial cells 798:835 human umbilical vein endothelial cells (HUVECs) treated with CAD sera and subjected to hypoxia in vitro 798:900 Expression of GALNT3 was also decreased in human umbilical vein endothelial cells (HUVECs) treated with CAD sera and subjected to hypoxia in vitro. 26714046 10 52 theme p38 1746:1748 arg1 activation 1755:1764 p38 MAPK activation 1746:1764 p38 MAPK activation 1746:1764 CONCLUSIONS Expression of GALNT3 was reduced in CAD patients, and down regulation of GALNT3 contributed to endothelial injury by promoting apoptosis and up-regulating the expression of MMP-2 and MMP-14 genes via p38 MAPK activation. 26714046 9 53 theme GALNT3 1400:1405 arg1 knockdown 1407:1415 GALNT3 knockdown 1400:1415 GALNT3 knockdown 1400:1415 Finally, the ratio of cytosolic p-p38 MAPK/p38 MAPK expression was significantly increased with GALNT3 knockdown and lower with GALNT3 overexpression, while the p38 MAPK inhibitor SB203580 blocked the effects of GALNT3 knockdown. 26714046 8 54 theme HUVECs 1115:1120 arg1 apoptosis 1122:1130 HUVECs apoptosis 1115:1130 HUVECs apoptosis 1115:1130 Conversely, overexpression of GALNT3 significantly inhibited HUVECs apoptosis and down-regulated the expression of MMP-2 and MMP-14 genes, in addition, overexpression of GALNT3 attenuated hypoxia-induced apoptosis and expression of MMP-2 and MMP-14. 26714046 8 55 theme genes 1186:1190 arg1 expression 1155:1164 the expression 1151:1164 the expression of MMP-2 and MMP-14 genes 1151:1190 Conversely, overexpression of GALNT3 significantly inhibited HUVECs apoptosis and down-regulated the expression of MMP-2 and MMP-14 genes, in addition, overexpression of GALNT3 attenuated hypoxia-induced apoptosis and expression of MMP-2 and MMP-14. 26714046 7 56 theme metalloproteinase-2 984:1002 arg1 expression 963:972 the expression 959:972 the expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-14 (MMP-14) 959:1051 Knockdown of GALNT3 promoted apoptosis and up-regulated the expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-14 (MMP-14). 26714046 10 57 theme genes 1736:1740 arg1 expression 1705:1714 the expression 1701:1714 the expression of MMP-2 and MMP-14 genes 1701:1740 CONCLUSIONS Expression of GALNT3 was reduced in CAD patients, and down regulation of GALNT3 contributed to endothelial injury by promoting apoptosis and up-regulating the expression of MMP-2 and MMP-14 genes via p38 MAPK activation. 26714046 5 58 theme CAD 690:692 arg1 n 704:704 n = 58 704:709 n = 58 704:709 METHODS AND RESULTS The GALNT3 mRNA level was decreased by 48.2% in CAD patients (n = 58), compared with that of controls (n = 120). 26714046 5 58 theme CAD 690:692 arg1 patients 694:701 CAD patients 690:701 CAD patients (n = 58) 690:710 METHODS AND RESULTS The GALNT3 mRNA level was decreased by 48.2% in CAD patients (n = 58), compared with that of controls (n = 120). 26714046 11 59 theme potential 1783:1791 arg1 target 1793:1798 a potential target 1781:1798 a potential target for future therapeutic intervention for CAD 1781:1842 GALNT3 may be a potential target for future therapeutic intervention for CAD. 26714046 11 59 theme potential 1783:1791 arg1 GALNT3 1767:1772 GALNT3 1767:1772 GALNT3 1767:1772 GALNT3 may be a potential target for future therapeutic intervention for CAD. 26714046 7 60 theme GALNT3 916:921 arg1 Knockdown 903:911 Knockdown 903:911 Knockdown of GALNT3 903:921 Knockdown of GALNT3 promoted apoptosis and up-regulated the expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-14 (MMP-14). 26714046 9 61 theme p38 1465:1467 arg1 SB203580 1484:1491 the p38 MAPK inhibitor SB203580 1461:1491 the p38 MAPK inhibitor SB203580 1461:1491 Finally, the ratio of cytosolic p-p38 MAPK/p38 MAPK expression was significantly increased with GALNT3 knockdown and lower with GALNT3 overexpression, while the p38 MAPK inhibitor SB203580 blocked the effects of GALNT3 knockdown. 26714046 1 62 theme polypeptide 145:155 arg1 transferase 180:190 polypeptide N-acetylgalactosaminyl transferase 3 145:192 polypeptide N-acetylgalactosaminyl transferase 3 (GalNAc-T3) 145:204 OBJECTIVE The GALNT3 gene encodes polypeptide N-acetylgalactosaminyl transferase 3 (GalNAc-T3), a member of the GalNAc-Ts family that transfers the N-acetylgalactosamine to the hydroxyl group of serine and threonine residue in the first step of O-linked oligosaccharide biosynthesis. 26714046 1 62 theme polypeptide 145:155 arg1 GalNAc-T3 195:203 GalNAc-T3 195:203 GalNAc-T3 195:203 OBJECTIVE The GALNT3 gene encodes polypeptide N-acetylgalactosaminyl transferase 3 (GalNAc-T3), a member of the GalNAc-Ts family that transfers the N-acetylgalactosamine to the hydroxyl group of serine and threonine residue in the first step of O-linked oligosaccharide biosynthesis. 26714046 1 62 theme polypeptide 145:155 arg1 gene 132:135 The GALNT3 gene 121:135 The GALNT3 gene 121:135 OBJECTIVE The GALNT3 gene encodes polypeptide N-acetylgalactosaminyl transferase 3 (GalNAc-T3), a member of the GalNAc-Ts family that transfers the N-acetylgalactosamine to the hydroxyl group of serine and threonine residue in the first step of O-linked oligosaccharide biosynthesis. 26714046 1 62 theme polypeptide 145:155 arg1 member 209:214 a member 207:214 a member of the GalNAc-Ts family that transfers the N-acetylgalactosamine to the hydroxyl group of serine and threonine residue in the first step of O-linked oligosaccharide biosynthesis 207:392 OBJECTIVE The GALNT3 gene encodes polypeptide N-acetylgalactosaminyl transferase 3 (GalNAc-T3), a member of the GalNAc-Ts family that transfers the N-acetylgalactosamine to the hydroxyl group of serine and threonine residue in the first step of O-linked oligosaccharide biosynthesis. 26714046 0 63 theme MAPK 87:90 arg1 pathway 102:108 p38 MAPK signaling pathway 83:108 p38 MAPK signaling pathway 83:108 Down regulation of GALNT3 contributes to endothelial cell injury via activation of p38 MAPK signaling pathway. 26714046 1 64 theme first 342:346 arg1 step 348:351 the first step 338:351 the first step of O-linked oligosaccharide biosynthesis 338:392 OBJECTIVE The GALNT3 gene encodes polypeptide N-acetylgalactosaminyl transferase 3 (GalNAc-T3), a member of the GalNAc-Ts family that transfers the N-acetylgalactosamine to the hydroxyl group of serine and threonine residue in the first step of O-linked oligosaccharide biosynthesis. 26714046 8 65 theme MMP-2 1286:1290 arg1 expression 1272:1281 expression 1272:1281 expression of MMP-2 and MMP-14 1272:1301 Conversely, overexpression of GALNT3 significantly inhibited HUVECs apoptosis and down-regulated the expression of MMP-2 and MMP-14 genes, in addition, overexpression of GALNT3 attenuated hypoxia-induced apoptosis and expression of MMP-2 and MMP-14. 26714046 8 65 theme MMP-2 1286:1290 arg1 apoptosis 1258:1266 hypoxia-induced apoptosis 1242:1266 hypoxia-induced apoptosis 1242:1266 Conversely, overexpression of GALNT3 significantly inhibited HUVECs apoptosis and down-regulated the expression of MMP-2 and MMP-14 genes, in addition, overexpression of GALNT3 attenuated hypoxia-induced apoptosis and expression of MMP-2 and MMP-14. 26714046 1 66 link O-linked 356:363 arg1 biosynthesis 381:392 O-linked oligosaccharide biosynthesis 356:392 O-linked oligosaccharide biosynthesis 356:392 OBJECTIVE The GALNT3 gene encodes polypeptide N-acetylgalactosaminyl transferase 3 (GalNAc-T3), a member of the GalNAc-Ts family that transfers the N-acetylgalactosamine to the hydroxyl group of serine and threonine residue in the first step of O-linked oligosaccharide biosynthesis. 26714046 0 67 theme pathway 102:108 arg1 activation 69:78 activation 69:78 activation of p38 MAPK signaling pathway 69:108 Down regulation of GALNT3 contributes to endothelial cell injury via activation of p38 MAPK signaling pathway. 26714046 1 68 dep OBJECTIVE 111:119 arg1 encodes 137:143 encodes 137:143 encodes polypeptide N-acetylgalactosaminyl transferase 3 (GalNAc-T3), a member of the GalNAc-Ts family that transfers the N-acetylgalactosamine to the hydroxyl group of serine and threonine residue in the first step of O-linked oligosaccharide biosynthesis 137:392 OBJECTIVE The GALNT3 gene encodes polypeptide N-acetylgalactosaminyl transferase 3 (GalNAc-T3), a member of the GalNAc-Ts family that transfers the N-acetylgalactosamine to the hydroxyl group of serine and threonine residue in the first step of O-linked oligosaccharide biosynthesis. 26714046 2 69 theme Emerging 395:402 arg1 evidences 404:412 Emerging evidences 395:412 Emerging evidences 395:412 Emerging evidences have linked GalNAc-Ts family to coronary artery disease (CAD). 26714046 4 70 from function 560:567 arg1 injury 614:619 endothelial injury 602:619 endothelial injury 602:619 The present study investigated the function and mechanisms of GALNT3 gene in endothelial injury. 26714046 1 71 theme oligosaccharide 365:379 arg1 biosynthesis 381:392 O-linked oligosaccharide biosynthesis 356:392 O-linked oligosaccharide biosynthesis 356:392 OBJECTIVE The GALNT3 gene encodes polypeptide N-acetylgalactosaminyl transferase 3 (GalNAc-T3), a member of the GalNAc-Ts family that transfers the N-acetylgalactosamine to the hydroxyl group of serine and threonine residue in the first step of O-linked oligosaccharide biosynthesis. 26714046 9 72 theme GALNT3 1516:1521 arg1 knockdown 1523:1531 GALNT3 knockdown 1516:1531 GALNT3 knockdown 1516:1531 Finally, the ratio of cytosolic p-p38 MAPK/p38 MAPK expression was significantly increased with GALNT3 knockdown and lower with GALNT3 overexpression, while the p38 MAPK inhibitor SB203580 blocked the effects of GALNT3 knockdown. 26714046 2 73 theme artery 455:460 arg1 CAD 471:473 CAD 471:473 CAD 471:473 Emerging evidences have linked GalNAc-Ts family to coronary artery disease (CAD). 26714046 2 73 theme artery 455:460 arg1 disease 462:468 coronary artery disease 446:468 coronary artery disease (CAD) 446:474 Emerging evidences have linked GalNAc-Ts family to coronary artery disease (CAD). 26714046 0 74 theme GALNT3 19:24 arg1 regulation 5:14 Down regulation 0:14 Down regulation of GALNT3 0:24 Down regulation of GALNT3 contributes to endothelial cell injury via activation of p38 MAPK signaling pathway. 26714046 2 75 theme GalNAc-Ts 426:434 arg1 family 436:441 GalNAc-Ts family 426:441 GalNAc-Ts family 426:441 Emerging evidences have linked GalNAc-Ts family to coronary artery disease (CAD). 26714046 0 76 theme cell 53:56 arg1 injury 58:63 endothelial cell injury 41:63 endothelial cell injury 41:63 Down regulation of GALNT3 contributes to endothelial cell injury via activation of p38 MAPK signaling pathway. 26714046 1 77 theme serine 306:311 arg1 serine 306:311 serine 306:311 serine 306:311 OBJECTIVE The GALNT3 gene encodes polypeptide N-acetylgalactosaminyl transferase 3 (GalNAc-T3), a member of the GalNAc-Ts family that transfers the N-acetylgalactosamine to the hydroxyl group of serine and threonine residue in the first step of O-linked oligosaccharide biosynthesis. 26714046 1 77 theme serine 306:311 arg1 group 297:301 the hydroxyl group 284:301 the hydroxyl group of serine and threonine residue 284:333 OBJECTIVE The GALNT3 gene encodes polypeptide N-acetylgalactosaminyl transferase 3 (GalNAc-T3), a member of the GalNAc-Ts family that transfers the N-acetylgalactosamine to the hydroxyl group of serine and threonine residue in the first step of O-linked oligosaccharide biosynthesis. 26714046 1 77 theme serine 306:311 arg1 threonine 317:325 threonine 317:325 threonine 317:325 OBJECTIVE The GALNT3 gene encodes polypeptide N-acetylgalactosaminyl transferase 3 (GalNAc-T3), a member of the GalNAc-Ts family that transfers the N-acetylgalactosamine to the hydroxyl group of serine and threonine residue in the first step of O-linked oligosaccharide biosynthesis. 26714046 2 78 attach linked 419:424 arg1 CAD 471:473 CAD 471:473 CAD 471:473 Emerging evidences have linked GalNAc-Ts family to coronary artery disease (CAD). 26714046 2 78 attach linked 419:424 arg1 disease 462:468 coronary artery disease 446:468 coronary artery disease (CAD) 446:474 Emerging evidences have linked GalNAc-Ts family to coronary artery disease (CAD). 26714046 2 78 attach linked 419:424 arg2 evidences 404:412 Emerging evidences 395:412 Emerging evidences 395:412 Emerging evidences have linked GalNAc-Ts family to coronary artery disease (CAD). 26714046 5 79 dep METHODS 622:628 arg1 decreased 668:676 decreased 668:676 decreased 668:676 METHODS AND RESULTS The GALNT3 mRNA level was decreased by 48.2% in CAD patients (n = 58), compared with that of controls (n = 120). 26714046 4 80 theme present 529:535 arg1 study 537:541 The present study 525:541 The present study 525:541 The present study investigated the function and mechanisms of GALNT3 gene in endothelial injury. 26714046 11 81 theme therapeutic 1811:1821 arg1 intervention 1823:1834 future therapeutic intervention 1804:1834 future therapeutic intervention for CAD 1804:1842 GALNT3 may be a potential target for future therapeutic intervention for CAD. 26714046 1 82 theme threonine 317:325 arg1 serine 306:311 serine 306:311 serine 306:311 OBJECTIVE The GALNT3 gene encodes polypeptide N-acetylgalactosaminyl transferase 3 (GalNAc-T3), a member of the GalNAc-Ts family that transfers the N-acetylgalactosamine to the hydroxyl group of serine and threonine residue in the first step of O-linked oligosaccharide biosynthesis. 26714046 1 82 theme threonine 317:325 arg1 group 297:301 the hydroxyl group 284:301 the hydroxyl group of serine and threonine residue 284:333 OBJECTIVE The GALNT3 gene encodes polypeptide N-acetylgalactosaminyl transferase 3 (GalNAc-T3), a member of the GalNAc-Ts family that transfers the N-acetylgalactosamine to the hydroxyl group of serine and threonine residue in the first step of O-linked oligosaccharide biosynthesis. 26714046 1 82 theme threonine 317:325 arg1 threonine 317:325 threonine 317:325 threonine 317:325 OBJECTIVE The GALNT3 gene encodes polypeptide N-acetylgalactosaminyl transferase 3 (GalNAc-T3), a member of the GalNAc-Ts family that transfers the N-acetylgalactosamine to the hydroxyl group of serine and threonine residue in the first step of O-linked oligosaccharide biosynthesis. 26714046 5 83 theme = 706:706 arg1 n 704:704 n = 58 704:709 n = 58 704:709 METHODS AND RESULTS The GALNT3 mRNA level was decreased by 48.2% in CAD patients (n = 58), compared with that of controls (n = 120). 26714046 5 83 theme = 706:706 arg1 patients 694:701 CAD patients 690:701 CAD patients (n = 58) 690:710 METHODS AND RESULTS The GALNT3 mRNA level was decreased by 48.2% in CAD patients (n = 58), compared with that of controls (n = 120). 26714046 8 84 theme MMP-14 1296:1301 arg1 expression 1272:1281 expression 1272:1281 expression of MMP-2 and MMP-14 1272:1301 Conversely, overexpression of GALNT3 significantly inhibited HUVECs apoptosis and down-regulated the expression of MMP-2 and MMP-14 genes, in addition, overexpression of GALNT3 attenuated hypoxia-induced apoptosis and expression of MMP-2 and MMP-14. 26714046 8 84 theme MMP-14 1296:1301 arg1 apoptosis 1258:1266 hypoxia-induced apoptosis 1242:1266 hypoxia-induced apoptosis 1242:1266 Conversely, overexpression of GALNT3 significantly inhibited HUVECs apoptosis and down-regulated the expression of MMP-2 and MMP-14 genes, in addition, overexpression of GALNT3 attenuated hypoxia-induced apoptosis and expression of MMP-2 and MMP-14. 26714046 10 85 theme endothelial 1641:1651 arg1 injury 1653:1658 endothelial injury 1641:1658 endothelial injury 1641:1658 CONCLUSIONS Expression of GALNT3 was reduced in CAD patients, and down regulation of GALNT3 contributed to endothelial injury by promoting apoptosis and up-regulating the expression of MMP-2 and MMP-14 genes via p38 MAPK activation. 26714046 9 86 theme cytosolic 1326:1334 arg1 expression 1356:1365 cytosolic p-p38 MAPK/p38 MAPK expression 1326:1365 cytosolic p-p38 MAPK/p38 MAPK expression 1326:1365 Finally, the ratio of cytosolic p-p38 MAPK/p38 MAPK expression was significantly increased with GALNT3 knockdown and lower with GALNT3 overexpression, while the p38 MAPK inhibitor SB203580 blocked the effects of GALNT3 knockdown. 26714046 10 87 theme down 1600:1603 arg1 regulation 1605:1614 down regulation 1600:1614 down regulation of GALNT3 1600:1624 CONCLUSIONS Expression of GALNT3 was reduced in CAD patients, and down regulation of GALNT3 contributed to endothelial injury by promoting apoptosis and up-regulating the expression of MMP-2 and MMP-14 genes via p38 MAPK activation. 26714046 1 88 theme family 233:238 arg1 transferase 180:190 polypeptide N-acetylgalactosaminyl transferase 3 145:192 polypeptide N-acetylgalactosaminyl transferase 3 (GalNAc-T3) 145:204 OBJECTIVE The GALNT3 gene encodes polypeptide N-acetylgalactosaminyl transferase 3 (GalNAc-T3), a member of the GalNAc-Ts family that transfers the N-acetylgalactosamine to the hydroxyl group of serine and threonine residue in the first step of O-linked oligosaccharide biosynthesis. 26714046 1 88 theme family 233:238 arg1 member 209:214 a member 207:214 a member of the GalNAc-Ts family that transfers the N-acetylgalactosamine to the hydroxyl group of serine and threonine residue in the first step of O-linked oligosaccharide biosynthesis 207:392 OBJECTIVE The GALNT3 gene encodes polypeptide N-acetylgalactosaminyl transferase 3 (GalNAc-T3), a member of the GalNAc-Ts family that transfers the N-acetylgalactosamine to the hydroxyl group of serine and threonine residue in the first step of O-linked oligosaccharide biosynthesis. 26714046 9 89 theme MAPK/p38 1342:1349 arg1 MAPK 1351:1354 p-p38 MAPK/p38 MAPK 1336:1354 cytosolic p-p38 MAPK/p38 MAPK expression 1326:1365 Finally, the ratio of cytosolic p-p38 MAPK/p38 MAPK expression was significantly increased with GALNT3 knockdown and lower with GALNT3 overexpression, while the p38 MAPK inhibitor SB203580 blocked the effects of GALNT3 knockdown. 24316969 1 0 dep cell 282:285 arg1 survival 298:305 survival 298:305 survival 298:305 There is a considerable resurgence of interest in the role of aerobic glycolysis in cancer; however, increased glycolysis is frequently viewed as a consequence of oncogenic events that drive malignant cell growth and survival. 24316969 1 0 dep cell 282:285 arg1 growth 287:292 growth 287:292 growth 287:292 There is a considerable resurgence of interest in the role of aerobic glycolysis in cancer; however, increased glycolysis is frequently viewed as a consequence of oncogenic events that drive malignant cell growth and survival. 24316969 4 1 theme glucose 710:716 arg1 uptake 718:723 glucose uptake 710:723 glucose uptake 710:723 Conversely, reduction of glucose uptake in malignant cells promoted the formation of organized and growth-arrested structures with basal polarity, and suppressed oncogenic pathways. 24316969 6 2 theme biosynthetic 1263:1274 arg1 pathway 1276:1282 the hexosamine biosynthetic pathway 1248:1282 the hexosamine biosynthetic pathway 1248:1282 Loss of epithelial integrity involved activation of RAP1 via exchange protein directly activated by cAMP (EPAC), involving also O-linked N-acetylglucosamine modification downstream of the hexosamine biosynthetic pathway. 24316969 1 3 theme aerobic 143:149 arg1 glycolysis 151:160 aerobic glycolysis 143:160 aerobic glycolysis 143:160 There is a considerable resurgence of interest in the role of aerobic glycolysis in cancer; however, increased glycolysis is frequently viewed as a consequence of oncogenic events that drive malignant cell growth and survival. 24316969 4 4 theme malignant 728:736 arg1 cells 738:742 malignant cells 728:742 malignant cells 728:742 Conversely, reduction of glucose uptake in malignant cells promoted the formation of organized and growth-arrested structures with basal polarity, and suppressed oncogenic pathways. 24316969 8 5 theme known 1449:1453 arg1 pathways 1465:1472 known oncogenic pathways 1449:1472 known oncogenic pathways 1449:1472 Our findings show that increased glucose uptake activates known oncogenic pathways to induce malignant phenotype, and provide possible targets for diagnosis and therapeutics. 24316969 7 6 theme soluble 1365:1371 arg1 cyclase 1382:1388 soluble adenylyl cyclase 1365:1388 soluble adenylyl cyclase 1365:1388 The former, in turn, was mediated by pyruvate kinase M2 (PKM2) interaction with soluble adenylyl cyclase. 24316969 1 7 theme glycolysis 151:160 arg1 role 135:138 the role 131:138 the role of aerobic glycolysis in cancer 131:170 There is a considerable resurgence of interest in the role of aerobic glycolysis in cancer; however, increased glycolysis is frequently viewed as a consequence of oncogenic events that drive malignant cell growth and survival. 24316969 4 8 with formation 757:765 arg1 polarity 822:829 basal polarity 816:829 basal polarity 816:829 Conversely, reduction of glucose uptake in malignant cells promoted the formation of organized and growth-arrested structures with basal polarity, and suppressed oncogenic pathways. 24316969 3 9 theme tissue 647:652 arg1 polarity 654:661 tissue polarity 647:661 tissue polarity 647:661 Overexpression of glucose transporter type 3 (GLUT3) in nonmalignant human breast cells activated known oncogenic signaling pathways, including EGFR, β1 integrin, MEK, and AKT, leading to loss of tissue polarity and increased growth. 24316969 7 10 theme pyruvate 1322:1329 arg1 PKM2 1342:1345 PKM2 1342:1345 PKM2 1342:1345 The former, in turn, was mediated by pyruvate kinase M2 (PKM2) interaction with soluble adenylyl cyclase. 24316969 7 10 theme pyruvate 1322:1329 arg1 M2 1338:1339 pyruvate kinase M2 1322:1339 pyruvate kinase M2 (PKM2) interaction with soluble adenylyl cyclase 1322:1388 The former, in turn, was mediated by pyruvate kinase M2 (PKM2) interaction with soluble adenylyl cyclase. 24316969 3 11 theme breast 526:531 arg1 cells 533:537 nonmalignant human breast cells 507:537 nonmalignant human breast cells 507:537 Overexpression of glucose transporter type 3 (GLUT3) in nonmalignant human breast cells activated known oncogenic signaling pathways, including EGFR, β1 integrin, MEK, and AKT, leading to loss of tissue polarity and increased growth. 24316969 7 12 from turn 1300:1303 arg1 former 1289:1294 former 1289:1294 former 1289:1294 The former, in turn, was mediated by pyruvate kinase M2 (PKM2) interaction with soluble adenylyl cyclase. 24316969 1 13 theme oncogenic 244:252 arg1 events 254:259 oncogenic events 244:259 oncogenic events that drive malignant cell growth and survival 244:305 There is a considerable resurgence of interest in the role of aerobic glycolysis in cancer; however, increased glycolysis is frequently viewed as a consequence of oncogenic events that drive malignant cell growth and survival. 24316969 6 14 theme RAP1 1116:1119 arg1 activation 1102:1111 activation 1102:1111 activation of RAP1 via exchange protein directly activated by cAMP (EPAC) 1102:1174 Loss of epithelial integrity involved activation of RAP1 via exchange protein directly activated by cAMP (EPAC), involving also O-linked N-acetylglucosamine modification downstream of the hexosamine biosynthetic pathway. 24316969 8 15 theme malignant 1484:1492 arg1 phenotype 1494:1502 malignant phenotype 1484:1502 malignant phenotype 1484:1502 Our findings show that increased glucose uptake activates known oncogenic pathways to induce malignant phenotype, and provide possible targets for diagnosis and therapeutics. 24316969 4 16 theme uptake 718:723 arg1 reduction 697:705 reduction 697:705 reduction of glucose uptake in malignant cells 697:742 Conversely, reduction of glucose uptake in malignant cells promoted the formation of organized and growth-arrested structures with basal polarity, and suppressed oncogenic pathways. 24316969 1 17 from role 135:138 arg1 cancer 165:170 cancer 165:170 cancer 165:170 There is a considerable resurgence of interest in the role of aerobic glycolysis in cancer; however, increased glycolysis is frequently viewed as a consequence of oncogenic events that drive malignant cell growth and survival. 24316969 2 18 theme increased 338:346 arg1 event 397:401 an oncogenic event 384:401 an oncogenic event in a physiologically relevant 3D culture model 384:448 Here we provide evidence that increased glycolytic activation itself can be an oncogenic event in a physiologically relevant 3D culture model. 24316969 2 18 theme increased 338:346 arg1 activation 359:368 increased glycolytic activation itself 338:375 increased glycolytic activation itself 338:375 Here we provide evidence that increased glycolytic activation itself can be an oncogenic event in a physiologically relevant 3D culture model. 24316969 1 19 theme events 254:259 arg1 glycolysis 192:201 increased glycolysis 182:201 increased glycolysis 182:201 There is a considerable resurgence of interest in the role of aerobic glycolysis in cancer; however, increased glycolysis is frequently viewed as a consequence of oncogenic events that drive malignant cell growth and survival. 24316969 1 19 theme events 254:259 arg1 consequence 229:239 a consequence 227:239 a consequence of oncogenic events that drive malignant cell growth and survival 227:305 There is a considerable resurgence of interest in the role of aerobic glycolysis in cancer; however, increased glycolysis is frequently viewed as a consequence of oncogenic events that drive malignant cell growth and survival. 24316969 5 20 theme mTOR 1049:1052 arg1 pathways 1054:1061 mTOR pathways 1049:1061 mTOR pathways 1049:1061 Unexpectedly and importantly, we found that unlike reported literature, in 3D the differences between "normal" and malignant phenotypes could not be explained by HIF-1α/2α, AMPK, or mTOR pathways. 24316969 4 21 theme basal 816:820 arg1 polarity 822:829 basal polarity 816:829 basal polarity 816:829 Conversely, reduction of glucose uptake in malignant cells promoted the formation of organized and growth-arrested structures with basal polarity, and suppressed oncogenic pathways. 24316969 3 22 theme nonmalignant 507:518 arg1 cells 533:537 nonmalignant human breast cells 507:537 nonmalignant human breast cells 507:537 Overexpression of glucose transporter type 3 (GLUT3) in nonmalignant human breast cells activated known oncogenic signaling pathways, including EGFR, β1 integrin, MEK, and AKT, leading to loss of tissue polarity and increased growth. 24316969 3 23 theme increased 667:675 arg1 growth 677:682 increased growth 667:682 increased growth 667:682 Overexpression of glucose transporter type 3 (GLUT3) in nonmalignant human breast cells activated known oncogenic signaling pathways, including EGFR, β1 integrin, MEK, and AKT, leading to loss of tissue polarity and increased growth. 24316969 6 24 theme N-acetylglucosamine 1201:1219 arg1 modification 1221:1232 O-linked N-acetylglucosamine modification 1192:1232 O-linked N-acetylglucosamine modification downstream of the hexosamine biosynthetic pathway 1192:1282 Loss of epithelial integrity involved activation of RAP1 via exchange protein directly activated by cAMP (EPAC), involving also O-linked N-acetylglucosamine modification downstream of the hexosamine biosynthetic pathway. 24316969 2 25 theme 3D 433:434 arg1 model 444:448 a physiologically relevant 3D culture model 406:448 a physiologically relevant 3D culture model 406:448 Here we provide evidence that increased glycolytic activation itself can be an oncogenic event in a physiologically relevant 3D culture model. 24316969 7 26 theme adenylyl 1373:1380 arg1 cyclase 1382:1388 soluble adenylyl cyclase 1365:1388 soluble adenylyl cyclase 1365:1388 The former, in turn, was mediated by pyruvate kinase M2 (PKM2) interaction with soluble adenylyl cyclase. 24316969 0 27 theme sugar 10:14 arg1 uptake 16:21 Increased sugar uptake 0:21 Increased sugar uptake 0:21 Increased sugar uptake promotes oncogenesis via EPAC/RAP1 and O-GlcNAc pathways. 24316969 3 28 theme growth 677:682 arg1 loss 639:642 loss 639:642 loss of tissue polarity and increased growth 639:682 Overexpression of glucose transporter type 3 (GLUT3) in nonmalignant human breast cells activated known oncogenic signaling pathways, including EGFR, β1 integrin, MEK, and AKT, leading to loss of tissue polarity and increased growth. 24316969 6 29 theme O-linked 1192:1199 arg1 N-acetylglucosamine 1201:1219 O-linked N-acetylglucosamine 1192:1219 O-linked N-acetylglucosamine modification downstream of the hexosamine biosynthetic pathway 1192:1282 Loss of epithelial integrity involved activation of RAP1 via exchange protein directly activated by cAMP (EPAC), involving also O-linked N-acetylglucosamine modification downstream of the hexosamine biosynthetic pathway. 24316969 3 30 theme oncogenic 555:563 arg1 pathways 575:582 known oncogenic signaling pathways 549:582 known oncogenic signaling pathways 549:582 Overexpression of glucose transporter type 3 (GLUT3) in nonmalignant human breast cells activated known oncogenic signaling pathways, including EGFR, β1 integrin, MEK, and AKT, leading to loss of tissue polarity and increased growth. 24316969 3 30 theme oncogenic 555:563 arg1 EGFR 595:598 EGFR 595:598 EGFR 595:598 Overexpression of glucose transporter type 3 (GLUT3) in nonmalignant human breast cells activated known oncogenic signaling pathways, including EGFR, β1 integrin, MEK, and AKT, leading to loss of tissue polarity and increased growth. 24316969 3 30 theme oncogenic 555:563 arg1 integrin 604:611 β1 integrin 601:611 β1 integrin 601:611 Overexpression of glucose transporter type 3 (GLUT3) in nonmalignant human breast cells activated known oncogenic signaling pathways, including EGFR, β1 integrin, MEK, and AKT, leading to loss of tissue polarity and increased growth. 24316969 3 30 theme oncogenic 555:563 arg1 MEK 614:616 MEK 614:616 MEK 614:616 Overexpression of glucose transporter type 3 (GLUT3) in nonmalignant human breast cells activated known oncogenic signaling pathways, including EGFR, β1 integrin, MEK, and AKT, leading to loss of tissue polarity and increased growth. 24316969 3 30 theme oncogenic 555:563 arg1 AKT 623:625 AKT 623:625 AKT 623:625 Overexpression of glucose transporter type 3 (GLUT3) in nonmalignant human breast cells activated known oncogenic signaling pathways, including EGFR, β1 integrin, MEK, and AKT, leading to loss of tissue polarity and increased growth. 24316969 0 31 theme Increased 0:8 arg1 uptake 16:21 Increased sugar uptake 0:21 Increased sugar uptake 0:21 Increased sugar uptake promotes oncogenesis via EPAC/RAP1 and O-GlcNAc pathways. 24316969 8 32 theme possible 1517:1524 arg1 targets 1526:1532 possible targets 1517:1532 possible targets for diagnosis and therapeutics 1517:1563 Our findings show that increased glucose uptake activates known oncogenic pathways to induce malignant phenotype, and provide possible targets for diagnosis and therapeutics. 24316969 6 33 theme integrity 1083:1091 arg1 Loss 1064:1067 Loss 1064:1067 Loss of epithelial integrity 1064:1091 Loss of epithelial integrity involved activation of RAP1 via exchange protein directly activated by cAMP (EPAC), involving also O-linked N-acetylglucosamine modification downstream of the hexosamine biosynthetic pathway. 24316969 4 34 from reduction 697:705 arg1 cells 738:742 malignant cells 728:742 malignant cells 728:742 Conversely, reduction of glucose uptake in malignant cells promoted the formation of organized and growth-arrested structures with basal polarity, and suppressed oncogenic pathways. 24316969 3 35 theme signaling 565:573 arg1 pathways 575:582 known oncogenic signaling pathways 549:582 known oncogenic signaling pathways 549:582 Overexpression of glucose transporter type 3 (GLUT3) in nonmalignant human breast cells activated known oncogenic signaling pathways, including EGFR, β1 integrin, MEK, and AKT, leading to loss of tissue polarity and increased growth. 24316969 3 35 theme signaling 565:573 arg1 EGFR 595:598 EGFR 595:598 EGFR 595:598 Overexpression of glucose transporter type 3 (GLUT3) in nonmalignant human breast cells activated known oncogenic signaling pathways, including EGFR, β1 integrin, MEK, and AKT, leading to loss of tissue polarity and increased growth. 24316969 3 35 theme signaling 565:573 arg1 integrin 604:611 β1 integrin 601:611 β1 integrin 601:611 Overexpression of glucose transporter type 3 (GLUT3) in nonmalignant human breast cells activated known oncogenic signaling pathways, including EGFR, β1 integrin, MEK, and AKT, leading to loss of tissue polarity and increased growth. 24316969 3 35 theme signaling 565:573 arg1 MEK 614:616 MEK 614:616 MEK 614:616 Overexpression of glucose transporter type 3 (GLUT3) in nonmalignant human breast cells activated known oncogenic signaling pathways, including EGFR, β1 integrin, MEK, and AKT, leading to loss of tissue polarity and increased growth. 24316969 3 35 theme signaling 565:573 arg1 AKT 623:625 AKT 623:625 AKT 623:625 Overexpression of glucose transporter type 3 (GLUT3) in nonmalignant human breast cells activated known oncogenic signaling pathways, including EGFR, β1 integrin, MEK, and AKT, leading to loss of tissue polarity and increased growth. 24316969 6 36 link O-linked 1192:1199 arg1 N-acetylglucosamine 1201:1219 O-linked N-acetylglucosamine 1192:1219 O-linked N-acetylglucosamine modification downstream of the hexosamine biosynthetic pathway 1192:1282 Loss of epithelial integrity involved activation of RAP1 via exchange protein directly activated by cAMP (EPAC), involving also O-linked N-acetylglucosamine modification downstream of the hexosamine biosynthetic pathway. 24316969 2 37 theme relevant 424:431 arg1 model 444:448 a physiologically relevant 3D culture model 406:448 a physiologically relevant 3D culture model 406:448 Here we provide evidence that increased glycolytic activation itself can be an oncogenic event in a physiologically relevant 3D culture model. 24316969 7 38 theme kinase 1331:1336 arg1 PKM2 1342:1345 PKM2 1342:1345 PKM2 1342:1345 The former, in turn, was mediated by pyruvate kinase M2 (PKM2) interaction with soluble adenylyl cyclase. 24316969 7 38 theme kinase 1331:1336 arg1 M2 1338:1339 pyruvate kinase M2 1322:1339 pyruvate kinase M2 (PKM2) interaction with soluble adenylyl cyclase 1322:1388 The former, in turn, was mediated by pyruvate kinase M2 (PKM2) interaction with soluble adenylyl cyclase. 24316969 1 39 theme considerable 92:103 arg1 resurgence 105:114 a considerable resurgence 90:114 a considerable resurgence of interest in the role of aerobic glycolysis in cancer 90:170 There is a considerable resurgence of interest in the role of aerobic glycolysis in cancer; however, increased glycolysis is frequently viewed as a consequence of oncogenic events that drive malignant cell growth and survival. 24316969 7 40 theme M2 1338:1339 arg1 interaction 1348:1358 pyruvate kinase M2 (PKM2) interaction 1322:1358 pyruvate kinase M2 (PKM2) interaction with soluble adenylyl cyclase 1322:1388 The former, in turn, was mediated by pyruvate kinase M2 (PKM2) interaction with soluble adenylyl cyclase. 24316969 5 41 theme reported 918:925 arg1 literature 927:936 reported literature 918:936 reported literature 918:936 Unexpectedly and importantly, we found that unlike reported literature, in 3D the differences between "normal" and malignant phenotypes could not be explained by HIF-1α/2α, AMPK, or mTOR pathways. 24316969 1 42 theme malignant 272:280 arg1 cell 282:285 malignant cell growth and survival 272:305 malignant cell growth and survival 272:305 There is a considerable resurgence of interest in the role of aerobic glycolysis in cancer; however, increased glycolysis is frequently viewed as a consequence of oncogenic events that drive malignant cell growth and survival. 24316969 6 43 theme exchange 1125:1132 arg1 protein 1134:1140 exchange protein 1125:1140 exchange protein directly activated by cAMP (EPAC) 1125:1174 Loss of epithelial integrity involved activation of RAP1 via exchange protein directly activated by cAMP (EPAC), involving also O-linked N-acetylglucosamine modification downstream of the hexosamine biosynthetic pathway. 24316969 3 44 theme known 549:553 arg1 pathways 575:582 known oncogenic signaling pathways 549:582 known oncogenic signaling pathways 549:582 Overexpression of glucose transporter type 3 (GLUT3) in nonmalignant human breast cells activated known oncogenic signaling pathways, including EGFR, β1 integrin, MEK, and AKT, leading to loss of tissue polarity and increased growth. 24316969 3 44 theme known 549:553 arg1 EGFR 595:598 EGFR 595:598 EGFR 595:598 Overexpression of glucose transporter type 3 (GLUT3) in nonmalignant human breast cells activated known oncogenic signaling pathways, including EGFR, β1 integrin, MEK, and AKT, leading to loss of tissue polarity and increased growth. 24316969 3 44 theme known 549:553 arg1 integrin 604:611 β1 integrin 601:611 β1 integrin 601:611 Overexpression of glucose transporter type 3 (GLUT3) in nonmalignant human breast cells activated known oncogenic signaling pathways, including EGFR, β1 integrin, MEK, and AKT, leading to loss of tissue polarity and increased growth. 24316969 3 44 theme known 549:553 arg1 MEK 614:616 MEK 614:616 MEK 614:616 Overexpression of glucose transporter type 3 (GLUT3) in nonmalignant human breast cells activated known oncogenic signaling pathways, including EGFR, β1 integrin, MEK, and AKT, leading to loss of tissue polarity and increased growth. 24316969 3 44 theme known 549:553 arg1 AKT 623:625 AKT 623:625 AKT 623:625 Overexpression of glucose transporter type 3 (GLUT3) in nonmalignant human breast cells activated known oncogenic signaling pathways, including EGFR, β1 integrin, MEK, and AKT, leading to loss of tissue polarity and increased growth. 24316969 1 45 theme increased 182:190 arg1 glycolysis 192:201 increased glycolysis 182:201 increased glycolysis 182:201 There is a considerable resurgence of interest in the role of aerobic glycolysis in cancer; however, increased glycolysis is frequently viewed as a consequence of oncogenic events that drive malignant cell growth and survival. 24316969 1 45 theme increased 182:190 arg1 consequence 229:239 a consequence 227:239 a consequence of oncogenic events that drive malignant cell growth and survival 227:305 There is a considerable resurgence of interest in the role of aerobic glycolysis in cancer; however, increased glycolysis is frequently viewed as a consequence of oncogenic events that drive malignant cell growth and survival. 24316969 6 46 theme epithelial 1072:1081 arg1 integrity 1083:1091 epithelial integrity 1072:1091 epithelial integrity 1072:1091 Loss of epithelial integrity involved activation of RAP1 via exchange protein directly activated by cAMP (EPAC), involving also O-linked N-acetylglucosamine modification downstream of the hexosamine biosynthetic pathway. 24316969 6 47 theme hexosamine 1252:1261 arg1 pathway 1276:1282 the hexosamine biosynthetic pathway 1248:1282 the hexosamine biosynthetic pathway 1248:1282 Loss of epithelial integrity involved activation of RAP1 via exchange protein directly activated by cAMP (EPAC), involving also O-linked N-acetylglucosamine modification downstream of the hexosamine biosynthetic pathway. 24316969 0 48 dep EPAC/RAP1 48:56 arg1 pathways 71:78 pathways 71:78 pathways 71:78 Increased sugar uptake promotes oncogenesis via EPAC/RAP1 and O-GlcNAc pathways. 24316969 2 49 theme oncogenic 387:395 arg1 event 397:401 an oncogenic event 384:401 an oncogenic event in a physiologically relevant 3D culture model 384:448 Here we provide evidence that increased glycolytic activation itself can be an oncogenic event in a physiologically relevant 3D culture model. 24316969 2 49 theme oncogenic 387:395 arg1 activation 359:368 increased glycolytic activation itself 338:375 increased glycolytic activation itself 338:375 Here we provide evidence that increased glycolytic activation itself can be an oncogenic event in a physiologically relevant 3D culture model. 24316969 4 50 theme structures 800:809 arg1 formation 757:765 the formation 753:765 the formation of organized and growth-arrested structures with basal polarity 753:829 Conversely, reduction of glucose uptake in malignant cells promoted the formation of organized and growth-arrested structures with basal polarity, and suppressed oncogenic pathways. 24316969 6 51 theme pathway 1276:1282 arg1 downstream 1234:1243 downstream 1234:1243 downstream 1234:1243 Loss of epithelial integrity involved activation of RAP1 via exchange protein directly activated by cAMP (EPAC), involving also O-linked N-acetylglucosamine modification downstream of the hexosamine biosynthetic pathway. 24316969 3 52 theme type 489:492 arg1 Overexpression 451:464 Overexpression 451:464 Overexpression of glucose transporter type 3 (GLUT3) in nonmalignant human breast cells 451:537 Overexpression of glucose transporter type 3 (GLUT3) in nonmalignant human breast cells activated known oncogenic signaling pathways, including EGFR, β1 integrin, MEK, and AKT, leading to loss of tissue polarity and increased growth. 24316969 6 53 theme downstream 1234:1243 arg1 modification 1221:1232 O-linked N-acetylglucosamine modification 1192:1232 O-linked N-acetylglucosamine modification downstream of the hexosamine biosynthetic pathway 1192:1282 Loss of epithelial integrity involved activation of RAP1 via exchange protein directly activated by cAMP (EPAC), involving also O-linked N-acetylglucosamine modification downstream of the hexosamine biosynthetic pathway. 24316969 8 54 theme oncogenic 1455:1463 arg1 pathways 1465:1472 known oncogenic pathways 1449:1472 known oncogenic pathways 1449:1472 Our findings show that increased glucose uptake activates known oncogenic pathways to induce malignant phenotype, and provide possible targets for diagnosis and therapeutics. 24316969 8 55 theme glucose 1424:1430 arg1 uptake 1432:1437 increased glucose uptake 1414:1437 increased glucose uptake 1414:1437 Our findings show that increased glucose uptake activates known oncogenic pathways to induce malignant phenotype, and provide possible targets for diagnosis and therapeutics. 24316969 4 56 theme growth-arrested 784:798 arg1 structures 800:809 organized and growth-arrested structures 770:809 organized and growth-arrested structures 770:809 Conversely, reduction of glucose uptake in malignant cells promoted the formation of organized and growth-arrested structures with basal polarity, and suppressed oncogenic pathways. 24316969 3 57 from Overexpression 451:464 arg1 cells 533:537 nonmalignant human breast cells 507:537 nonmalignant human breast cells 507:537 Overexpression of glucose transporter type 3 (GLUT3) in nonmalignant human breast cells activated known oncogenic signaling pathways, including EGFR, β1 integrin, MEK, and AKT, leading to loss of tissue polarity and increased growth. 24316969 1 58 theme interest 119:126 arg1 resurgence 105:114 a considerable resurgence 90:114 a considerable resurgence of interest in the role of aerobic glycolysis in cancer 90:170 There is a considerable resurgence of interest in the role of aerobic glycolysis in cancer; however, increased glycolysis is frequently viewed as a consequence of oncogenic events that drive malignant cell growth and survival. 24316969 5 59 theme malignant 982:990 arg1 phenotypes 992:1001 malignant phenotypes 982:1001 malignant phenotypes 982:1001 Unexpectedly and importantly, we found that unlike reported literature, in 3D the differences between "normal" and malignant phenotypes could not be explained by HIF-1α/2α, AMPK, or mTOR pathways. 24316969 8 60 theme increased 1414:1422 arg1 uptake 1432:1437 increased glucose uptake 1414:1437 increased glucose uptake 1414:1437 Our findings show that increased glucose uptake activates known oncogenic pathways to induce malignant phenotype, and provide possible targets for diagnosis and therapeutics. 24316969 4 61 theme organized 770:778 arg1 structures 800:809 organized and growth-arrested structures 770:809 organized and growth-arrested structures 770:809 Conversely, reduction of glucose uptake in malignant cells promoted the formation of organized and growth-arrested structures with basal polarity, and suppressed oncogenic pathways. 24316969 3 62 theme glucose 469:475 arg1 type 489:492 glucose transporter type 3 469:494 glucose transporter type 3 (GLUT3) 469:502 Overexpression of glucose transporter type 3 (GLUT3) in nonmalignant human breast cells activated known oncogenic signaling pathways, including EGFR, β1 integrin, MEK, and AKT, leading to loss of tissue polarity and increased growth. 24316969 3 62 theme glucose 469:475 arg1 GLUT3 497:501 GLUT3 497:501 GLUT3 497:501 Overexpression of glucose transporter type 3 (GLUT3) in nonmalignant human breast cells activated known oncogenic signaling pathways, including EGFR, β1 integrin, MEK, and AKT, leading to loss of tissue polarity and increased growth. 24316969 1 63 from resurgence 105:114 arg1 role 135:138 the role 131:138 the role of aerobic glycolysis in cancer 131:170 There is a considerable resurgence of interest in the role of aerobic glycolysis in cancer; however, increased glycolysis is frequently viewed as a consequence of oncogenic events that drive malignant cell growth and survival. 24316969 3 64 theme human 520:524 arg1 cells 533:537 nonmalignant human breast cells 507:537 nonmalignant human breast cells 507:537 Overexpression of glucose transporter type 3 (GLUT3) in nonmalignant human breast cells activated known oncogenic signaling pathways, including EGFR, β1 integrin, MEK, and AKT, leading to loss of tissue polarity and increased growth. 24316969 2 65 from event 397:401 arg1 model 444:448 a physiologically relevant 3D culture model 406:448 a physiologically relevant 3D culture model 406:448 Here we provide evidence that increased glycolytic activation itself can be an oncogenic event in a physiologically relevant 3D culture model. 24316969 3 66 theme transporter 477:487 arg1 type 489:492 glucose transporter type 3 469:494 glucose transporter type 3 (GLUT3) 469:502 Overexpression of glucose transporter type 3 (GLUT3) in nonmalignant human breast cells activated known oncogenic signaling pathways, including EGFR, β1 integrin, MEK, and AKT, leading to loss of tissue polarity and increased growth. 24316969 3 66 theme transporter 477:487 arg1 GLUT3 497:501 GLUT3 497:501 GLUT3 497:501 Overexpression of glucose transporter type 3 (GLUT3) in nonmalignant human breast cells activated known oncogenic signaling pathways, including EGFR, β1 integrin, MEK, and AKT, leading to loss of tissue polarity and increased growth. 24316969 4 67 theme oncogenic 847:855 arg1 pathways 857:864 oncogenic pathways 847:864 oncogenic pathways 847:864 Conversely, reduction of glucose uptake in malignant cells promoted the formation of organized and growth-arrested structures with basal polarity, and suppressed oncogenic pathways. 24316969 7 68 with interaction 1348:1358 arg1 cyclase 1382:1388 soluble adenylyl cyclase 1365:1388 soluble adenylyl cyclase 1365:1388 The former, in turn, was mediated by pyruvate kinase M2 (PKM2) interaction with soluble adenylyl cyclase. 24316969 5 69 theme normal 970:975 arg1 " 976:976 "normal" 969:976 "normal" 969:976 Unexpectedly and importantly, we found that unlike reported literature, in 3D the differences between "normal" and malignant phenotypes could not be explained by HIF-1α/2α, AMPK, or mTOR pathways. 24316969 7 70 from former 1289:1294 arg1 turn 1300:1303 turn 1300:1303 turn 1300:1303 The former, in turn, was mediated by pyruvate kinase M2 (PKM2) interaction with soluble adenylyl cyclase. 24316969 2 71 theme culture 436:442 arg1 model 444:448 a physiologically relevant 3D culture model 406:448 a physiologically relevant 3D culture model 406:448 Here we provide evidence that increased glycolytic activation itself can be an oncogenic event in a physiologically relevant 3D culture model. 24316969 3 72 theme polarity 654:661 arg1 loss 639:642 loss 639:642 loss of tissue polarity and increased growth 639:682 Overexpression of glucose transporter type 3 (GLUT3) in nonmalignant human breast cells activated known oncogenic signaling pathways, including EGFR, β1 integrin, MEK, and AKT, leading to loss of tissue polarity and increased growth. 24316969 3 73 theme β1 601:602 arg1 integrin 604:611 β1 integrin 601:611 β1 integrin 601:611 Overexpression of glucose transporter type 3 (GLUT3) in nonmalignant human breast cells activated known oncogenic signaling pathways, including EGFR, β1 integrin, MEK, and AKT, leading to loss of tissue polarity and increased growth. 24316969 2 74 theme glycolytic 348:357 arg1 event 397:401 an oncogenic event 384:401 an oncogenic event in a physiologically relevant 3D culture model 384:448 Here we provide evidence that increased glycolytic activation itself can be an oncogenic event in a physiologically relevant 3D culture model. 24316969 2 74 theme glycolytic 348:357 arg1 activation 359:368 increased glycolytic activation itself 338:375 increased glycolytic activation itself 338:375 Here we provide evidence that increased glycolytic activation itself can be an oncogenic event in a physiologically relevant 3D culture model. 28843855 4 0 theme thioredoxin-interacting 589:611 arg1 protein 613:619 thioredoxin-interacting protein 589:619 thioredoxin-interacting protein 589:619 Western blot analysis showed that levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) and other related proteins such as carbohydrate-responsive element-binding protein (ChREBP) and thioredoxin-interacting protein (TXNIP) were significantly increased, and nuclear factor kappaB (NF-κB) and poly (ADP-ribose) polymerase (PARP) were activated in the diabetic retinas or retinal pigment epithelial (RPE) cells exposed to high glucose compared to controls. 28843855 4 1 theme Western 389:395 arg1 analysis 402:409 Western blot analysis 389:409 Western blot analysis 389:409 Western blot analysis showed that levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) and other related proteins such as carbohydrate-responsive element-binding protein (ChREBP) and thioredoxin-interacting protein (TXNIP) were significantly increased, and nuclear factor kappaB (NF-κB) and poly (ADP-ribose) polymerase (PARP) were activated in the diabetic retinas or retinal pigment epithelial (RPE) cells exposed to high glucose compared to controls. 28843855 6 2 theme control 1268:1274 arg1 retinas 1276:1282 control retinas 1268:1282 control retinas 1268:1282 Double immunofluorescence analysis revealed increased co-localization of terminal deoxynucleotide transferase-mediated dUTP nick-end labelling (TUNEL)-positive ganglion cells and OGT, ChREBP, TXNIP, or NF-κB in diabetic retinas compared to control retinas. 28843855 6 3 theme cells 1197:1201 arg1 co-localization 1082:1096 increased co-localization 1072:1096 increased co-localization of terminal deoxynucleotide transferase-mediated dUTP nick-end labelling (TUNEL)-positive ganglion cells 1072:1201 Double immunofluorescence analysis revealed increased co-localization of terminal deoxynucleotide transferase-mediated dUTP nick-end labelling (TUNEL)-positive ganglion cells and OGT, ChREBP, TXNIP, or NF-κB in diabetic retinas compared to control retinas. 28843855 6 3 theme cells 1197:1201 arg1 TXNIP 1220:1224 TXNIP 1220:1224 TXNIP 1220:1224 Double immunofluorescence analysis revealed increased co-localization of terminal deoxynucleotide transferase-mediated dUTP nick-end labelling (TUNEL)-positive ganglion cells and OGT, ChREBP, TXNIP, or NF-κB in diabetic retinas compared to control retinas. 28843855 6 3 theme cells 1197:1201 arg1 NF-κB 1230:1234 NF-κB 1230:1234 NF-κB 1230:1234 Double immunofluorescence analysis revealed increased co-localization of terminal deoxynucleotide transferase-mediated dUTP nick-end labelling (TUNEL)-positive ganglion cells and OGT, ChREBP, TXNIP, or NF-κB in diabetic retinas compared to control retinas. 28843855 6 3 theme cells 1197:1201 arg1 ChREBP 1212:1217 ChREBP 1212:1217 ChREBP 1212:1217 Double immunofluorescence analysis revealed increased co-localization of terminal deoxynucleotide transferase-mediated dUTP nick-end labelling (TUNEL)-positive ganglion cells and OGT, ChREBP, TXNIP, or NF-κB in diabetic retinas compared to control retinas. 28843855 6 3 theme cells 1197:1201 arg1 OGT 1207:1209 OGT 1207:1209 OGT 1207:1209 Double immunofluorescence analysis revealed increased co-localization of terminal deoxynucleotide transferase-mediated dUTP nick-end labelling (TUNEL)-positive ganglion cells and OGT, ChREBP, TXNIP, or NF-κB in diabetic retinas compared to control retinas. 28843855 7 4 theme more 1464:1467 arg1 death 1474:1478 more cell death 1464:1478 more cell death 1464:1478 Co-immunoprecipitation analysis showed that interaction between OGT and ChREBP or NF-κB was increased in diabetic retinas compared to control retinas, and this was accompanied by more cell death. 28843855 6 5 theme -positive 1178:1186 arg1 cells 1197:1201 terminal deoxynucleotide transferase-mediated dUTP nick-end labelling (TUNEL)-positive ganglion cells 1101:1201 terminal deoxynucleotide transferase-mediated dUTP nick-end labelling (TUNEL)-positive ganglion cells 1101:1201 Double immunofluorescence analysis revealed increased co-localization of terminal deoxynucleotide transferase-mediated dUTP nick-end labelling (TUNEL)-positive ganglion cells and OGT, ChREBP, TXNIP, or NF-κB in diabetic retinas compared to control retinas. 28843855 6 6 theme diabetic 1239:1246 arg1 retinas 1248:1254 diabetic retinas 1239:1254 diabetic retinas 1239:1254 Double immunofluorescence analysis revealed increased co-localization of terminal deoxynucleotide transferase-mediated dUTP nick-end labelling (TUNEL)-positive ganglion cells and OGT, ChREBP, TXNIP, or NF-κB in diabetic retinas compared to control retinas. 28843855 1 7 theme developed 166:174 arg1 world 176:180 the developed world 162:180 the developed world 162:180 Retinal degeneration is an early feature of diabetic retinopathy, the major cause of blindness in the developed world. 28843855 3 8 with mice 346:349 arg1 diabetes 379:386 streptozotocin-induced diabetes 356:386 streptozotocin-induced diabetes 356:386 Metformin was orally administered to control mice or mice with streptozotocin-induced diabetes. 28843855 2 9 theme diabetic 278:285 arg1 mice 287:290 diabetic mice 278:290 diabetic mice 278:290 Here we investigated how the widely used antidiabetic drug metformin reduces retinal injury in diabetic mice. 28843855 4 10 theme β-N-acetylglucosamine 442:462 arg1 OGT 488:490 OGT 488:490 OGT 488:490 Western blot analysis showed that levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) and other related proteins such as carbohydrate-responsive element-binding protein (ChREBP) and thioredoxin-interacting protein (TXNIP) were significantly increased, and nuclear factor kappaB (NF-κB) and poly (ADP-ribose) polymerase (PARP) were activated in the diabetic retinas or retinal pigment epithelial (RPE) cells exposed to high glucose compared to controls. 28843855 4 10 theme β-N-acetylglucosamine 442:462 arg1 transferase 475:485 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase 433:485 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) 433:491 Western blot analysis showed that levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) and other related proteins such as carbohydrate-responsive element-binding protein (ChREBP) and thioredoxin-interacting protein (TXNIP) were significantly increased, and nuclear factor kappaB (NF-κB) and poly (ADP-ribose) polymerase (PARP) were activated in the diabetic retinas or retinal pigment epithelial (RPE) cells exposed to high glucose compared to controls. 28843855 4 11 theme nuclear 663:669 arg1 kappaB 678:683 nuclear factor kappaB 663:683 nuclear factor kappaB (NF-κB) 663:691 Western blot analysis showed that levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) and other related proteins such as carbohydrate-responsive element-binding protein (ChREBP) and thioredoxin-interacting protein (TXNIP) were significantly increased, and nuclear factor kappaB (NF-κB) and poly (ADP-ribose) polymerase (PARP) were activated in the diabetic retinas or retinal pigment epithelial (RPE) cells exposed to high glucose compared to controls. 28843855 4 11 theme nuclear 663:669 arg1 NF-κB 686:690 NF-κB 686:690 NF-κB 686:690 Western blot analysis showed that levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) and other related proteins such as carbohydrate-responsive element-binding protein (ChREBP) and thioredoxin-interacting protein (TXNIP) were significantly increased, and nuclear factor kappaB (NF-κB) and poly (ADP-ribose) polymerase (PARP) were activated in the diabetic retinas or retinal pigment epithelial (RPE) cells exposed to high glucose compared to controls. 28843855 7 12 dep increased 1377:1385 arg1 compared 1407:1414 compared 1407:1414 compared to control retinas 1407:1433 Co-immunoprecipitation analysis showed that interaction between OGT and ChREBP or NF-κB was increased in diabetic retinas compared to control retinas, and this was accompanied by more cell death. 28843855 4 13 theme O-GlcNAc 465:472 arg1 OGT 488:490 OGT 488:490 OGT 488:490 Western blot analysis showed that levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) and other related proteins such as carbohydrate-responsive element-binding protein (ChREBP) and thioredoxin-interacting protein (TXNIP) were significantly increased, and nuclear factor kappaB (NF-κB) and poly (ADP-ribose) polymerase (PARP) were activated in the diabetic retinas or retinal pigment epithelial (RPE) cells exposed to high glucose compared to controls. 28843855 4 13 theme O-GlcNAc 465:472 arg1 transferase 475:485 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase 433:485 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) 433:491 Western blot analysis showed that levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) and other related proteins such as carbohydrate-responsive element-binding protein (ChREBP) and thioredoxin-interacting protein (TXNIP) were significantly increased, and nuclear factor kappaB (NF-κB) and poly (ADP-ribose) polymerase (PARP) were activated in the diabetic retinas or retinal pigment epithelial (RPE) cells exposed to high glucose compared to controls. 28843855 5 14 theme elevated 1002:1009 arg1 O-GlcNAcylation 1011:1025 elevated O-GlcNAcylation 1002:1025 elevated O-GlcNAcylation 1002:1025 More importantly, RPE cells exposed to high glucose and treated with thiamet-G had higher levels of those proteins, demonstrating the role of elevated O-GlcNAcylation. 28843855 1 15 theme diabetic 108:115 arg1 retinopathy 117:127 diabetic retinopathy 108:127 diabetic retinopathy 108:127 Retinal degeneration is an early feature of diabetic retinopathy, the major cause of blindness in the developed world. 28843855 2 16 theme drug 237:240 arg1 metformin 242:250 the widely used antidiabetic drug metformin 208:250 the widely used antidiabetic drug metformin 208:250 Here we investigated how the widely used antidiabetic drug metformin reduces retinal injury in diabetic mice. 28843855 5 17 theme high 899:902 arg1 glucose 904:910 high glucose 899:910 high glucose 899:910 More importantly, RPE cells exposed to high glucose and treated with thiamet-G had higher levels of those proteins, demonstrating the role of elevated O-GlcNAcylation. 28843855 5 18 theme higher 943:948 arg1 levels 950:955 higher levels 943:955 higher levels of those proteins 943:973 More importantly, RPE cells exposed to high glucose and treated with thiamet-G had higher levels of those proteins, demonstrating the role of elevated O-GlcNAcylation. 28843855 2 19 theme used 219:222 arg1 metformin 242:250 the widely used antidiabetic drug metformin 208:250 the widely used antidiabetic drug metformin 208:250 Here we investigated how the widely used antidiabetic drug metformin reduces retinal injury in diabetic mice. 28843855 1 20 theme major 134:138 arg1 cause 140:144 the major cause 130:144 the major cause of blindness in the developed world 130:180 Retinal degeneration is an early feature of diabetic retinopathy, the major cause of blindness in the developed world. 28843855 1 20 theme major 134:138 arg1 feature 97:103 an early feature 88:103 an early feature of diabetic retinopathy 88:127 Retinal degeneration is an early feature of diabetic retinopathy, the major cause of blindness in the developed world. 28843855 1 21 from cause 140:144 arg1 world 176:180 the developed world 162:180 the developed world 162:180 Retinal degeneration is an early feature of diabetic retinopathy, the major cause of blindness in the developed world. 28843855 8 22 from co-localization 1552:1566 arg1 levels 1536:1541 protein levels 1528:1541 protein levels 1528:1541 Notably, metformin attenuated the increases in protein levels; reduced co-localization of TUNEL-positive ganglion cells and OGT, ChREBP, TXNIP, or NF-κB; and reduced interaction between OGT and ChREBP or NF-κB. 28843855 9 23 theme mechanisms 1753:1762 arg1 one 1742:1744 one 1742:1744 one 1742:1744 Our results indicate that OGT inhibition might be one of the mechanisms by which metformin decreases retinal cell death. 28843855 9 23 theme mechanisms 1753:1762 arg1 mechanisms 1753:1762 the mechanisms 1749:1762 the mechanisms by which metformin decreases retinal cell death 1749:1810 Our results indicate that OGT inhibition might be one of the mechanisms by which metformin decreases retinal cell death. 28843855 4 24 theme related 503:509 arg1 protein 613:619 thioredoxin-interacting protein 589:619 thioredoxin-interacting protein 589:619 Western blot analysis showed that levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) and other related proteins such as carbohydrate-responsive element-binding protein (ChREBP) and thioredoxin-interacting protein (TXNIP) were significantly increased, and nuclear factor kappaB (NF-κB) and poly (ADP-ribose) polymerase (PARP) were activated in the diabetic retinas or retinal pigment epithelial (RPE) cells exposed to high glucose compared to controls. 28843855 4 24 theme related 503:509 arg1 protein 568:574 carbohydrate-responsive element-binding protein 528:574 carbohydrate-responsive element-binding protein (ChREBP) 528:583 Western blot analysis showed that levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) and other related proteins such as carbohydrate-responsive element-binding protein (ChREBP) and thioredoxin-interacting protein (TXNIP) were significantly increased, and nuclear factor kappaB (NF-κB) and poly (ADP-ribose) polymerase (PARP) were activated in the diabetic retinas or retinal pigment epithelial (RPE) cells exposed to high glucose compared to controls. 28843855 4 24 theme related 503:509 arg1 proteins 511:518 other related proteins 497:518 other related proteins such as carbohydrate-responsive element-binding protein (ChREBP) and thioredoxin-interacting protein (TXNIP) 497:627 Western blot analysis showed that levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) and other related proteins such as carbohydrate-responsive element-binding protein (ChREBP) and thioredoxin-interacting protein (TXNIP) were significantly increased, and nuclear factor kappaB (NF-κB) and poly (ADP-ribose) polymerase (PARP) were activated in the diabetic retinas or retinal pigment epithelial (RPE) cells exposed to high glucose compared to controls. 28843855 4 25 theme transferase 475:485 arg1 levels 423:428 levels 423:428 levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) and other related proteins such as carbohydrate-responsive element-binding protein (ChREBP) and thioredoxin-interacting protein (TXNIP) 423:627 Western blot analysis showed that levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) and other related proteins such as carbohydrate-responsive element-binding protein (ChREBP) and thioredoxin-interacting protein (TXNIP) were significantly increased, and nuclear factor kappaB (NF-κB) and poly (ADP-ribose) polymerase (PARP) were activated in the diabetic retinas or retinal pigment epithelial (RPE) cells exposed to high glucose compared to controls. 28843855 5 26 dep cells 882:886 arg1 treated 916:922 treated 916:922 treated with thiamet-G 916:937 More importantly, RPE cells exposed to high glucose and treated with thiamet-G had higher levels of those proteins, demonstrating the role of elevated O-GlcNAcylation. 28843855 5 26 dep cells 882:886 arg1 exposed 888:894 exposed 888:894 exposed to high glucose 888:910 More importantly, RPE cells exposed to high glucose and treated with thiamet-G had higher levels of those proteins, demonstrating the role of elevated O-GlcNAcylation. 28843855 5 27 theme RPE 878:880 arg1 cells 882:886 RPE cells 878:886 RPE cells exposed to high glucose and treated with thiamet-G 878:937 More importantly, RPE cells exposed to high glucose and treated with thiamet-G had higher levels of those proteins, demonstrating the role of elevated O-GlcNAcylation. 28843855 8 28 from increases 1515:1523 arg1 levels 1536:1541 protein levels 1528:1541 protein levels 1528:1541 Notably, metformin attenuated the increases in protein levels; reduced co-localization of TUNEL-positive ganglion cells and OGT, ChREBP, TXNIP, or NF-κB; and reduced interaction between OGT and ChREBP or NF-κB. 28843855 6 29 theme immunofluorescence 1035:1052 arg1 analysis 1054:1061 Double immunofluorescence analysis 1028:1061 Double immunofluorescence analysis 1028:1061 Double immunofluorescence analysis revealed increased co-localization of terminal deoxynucleotide transferase-mediated dUTP nick-end labelling (TUNEL)-positive ganglion cells and OGT, ChREBP, TXNIP, or NF-κB in diabetic retinas compared to control retinas. 28843855 9 30 theme cell 1801:1804 arg1 death 1806:1810 retinal cell death 1793:1810 retinal cell death 1793:1810 Our results indicate that OGT inhibition might be one of the mechanisms by which metformin decreases retinal cell death. 28843855 8 31 theme TUNEL-positive 1571:1584 arg1 cells 1595:1599 TUNEL-positive ganglion cells 1571:1599 TUNEL-positive ganglion cells 1571:1599 Notably, metformin attenuated the increases in protein levels; reduced co-localization of TUNEL-positive ganglion cells and OGT, ChREBP, TXNIP, or NF-κB; and reduced interaction between OGT and ChREBP or NF-κB. 28843855 4 32 theme RPE 803:805 arg1 cells 808:812 retinal pigment epithelial (RPE) cells 775:812 retinal pigment epithelial (RPE) cells 775:812 Western blot analysis showed that levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) and other related proteins such as carbohydrate-responsive element-binding protein (ChREBP) and thioredoxin-interacting protein (TXNIP) were significantly increased, and nuclear factor kappaB (NF-κB) and poly (ADP-ribose) polymerase (PARP) were activated in the diabetic retinas or retinal pigment epithelial (RPE) cells exposed to high glucose compared to controls. 28843855 0 33 theme cell 35:38 arg1 death 40:44 retinal cell death 27:44 retinal cell death in diabetic mice 27:61 Metformin protects against retinal cell death in diabetic mice. 28843855 8 34 theme cells 1595:1599 arg1 increases 1515:1523 the increases 1511:1523 the increases in protein levels 1511:1541 Notably, metformin attenuated the increases in protein levels; reduced co-localization of TUNEL-positive ganglion cells and OGT, ChREBP, TXNIP, or NF-κB; and reduced interaction between OGT and ChREBP or NF-κB. 28843855 8 34 theme cells 1595:1599 arg1 co-localization 1552:1566 reduced co-localization 1544:1566 reduced co-localization of TUNEL-positive ganglion cells and OGT, ChREBP, TXNIP, or NF-κB 1544:1632 Notably, metformin attenuated the increases in protein levels; reduced co-localization of TUNEL-positive ganglion cells and OGT, ChREBP, TXNIP, or NF-κB; and reduced interaction between OGT and ChREBP or NF-κB. 28843855 8 34 theme cells 1595:1599 arg1 interaction 1647:1657 reduced interaction 1639:1657 reduced interaction between OGT and ChREBP or NF-κB 1639:1689 Notably, metformin attenuated the increases in protein levels; reduced co-localization of TUNEL-positive ganglion cells and OGT, ChREBP, TXNIP, or NF-κB; and reduced interaction between OGT and ChREBP or NF-κB. 28843855 6 35 theme nick-end 1152:1159 arg1 TUNEL 1172:1176 TUNEL 1172:1176 TUNEL 1172:1176 Double immunofluorescence analysis revealed increased co-localization of terminal deoxynucleotide transferase-mediated dUTP nick-end labelling (TUNEL)-positive ganglion cells and OGT, ChREBP, TXNIP, or NF-κB in diabetic retinas compared to control retinas. 28843855 6 35 theme nick-end 1152:1159 arg1 labelling 1161:1169 terminal deoxynucleotide transferase-mediated dUTP nick-end labelling 1101:1169 terminal deoxynucleotide transferase-mediated dUTP nick-end labelling (TUNEL)-positive ganglion cells 1101:1201 Double immunofluorescence analysis revealed increased co-localization of terminal deoxynucleotide transferase-mediated dUTP nick-end labelling (TUNEL)-positive ganglion cells and OGT, ChREBP, TXNIP, or NF-κB in diabetic retinas compared to control retinas. 28843855 8 36 theme OGT 1605:1607 arg1 increases 1515:1523 the increases 1511:1523 the increases in protein levels 1511:1541 Notably, metformin attenuated the increases in protein levels; reduced co-localization of TUNEL-positive ganglion cells and OGT, ChREBP, TXNIP, or NF-κB; and reduced interaction between OGT and ChREBP or NF-κB. 28843855 8 36 theme OGT 1605:1607 arg1 co-localization 1552:1566 reduced co-localization 1544:1566 reduced co-localization of TUNEL-positive ganglion cells and OGT, ChREBP, TXNIP, or NF-κB 1544:1632 Notably, metformin attenuated the increases in protein levels; reduced co-localization of TUNEL-positive ganglion cells and OGT, ChREBP, TXNIP, or NF-κB; and reduced interaction between OGT and ChREBP or NF-κB. 28843855 8 36 theme OGT 1605:1607 arg1 interaction 1647:1657 reduced interaction 1639:1657 reduced interaction between OGT and ChREBP or NF-κB 1639:1689 Notably, metformin attenuated the increases in protein levels; reduced co-localization of TUNEL-positive ganglion cells and OGT, ChREBP, TXNIP, or NF-κB; and reduced interaction between OGT and ChREBP or NF-κB. 28843855 4 37 theme retinal 775:781 arg1 cells 808:812 retinal pigment epithelial (RPE) cells 775:812 retinal pigment epithelial (RPE) cells 775:812 Western blot analysis showed that levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) and other related proteins such as carbohydrate-responsive element-binding protein (ChREBP) and thioredoxin-interacting protein (TXNIP) were significantly increased, and nuclear factor kappaB (NF-κB) and poly (ADP-ribose) polymerase (PARP) were activated in the diabetic retinas or retinal pigment epithelial (RPE) cells exposed to high glucose compared to controls. 28843855 8 38 theme reduced 1639:1645 arg1 interaction 1647:1657 reduced interaction 1639:1657 reduced interaction between OGT and ChREBP or NF-κB 1639:1689 Notably, metformin attenuated the increases in protein levels; reduced co-localization of TUNEL-positive ganglion cells and OGT, ChREBP, TXNIP, or NF-κB; and reduced interaction between OGT and ChREBP or NF-κB. 28843855 6 39 theme transferase-mediated 1126:1145 arg1 TUNEL 1172:1176 TUNEL 1172:1176 TUNEL 1172:1176 Double immunofluorescence analysis revealed increased co-localization of terminal deoxynucleotide transferase-mediated dUTP nick-end labelling (TUNEL)-positive ganglion cells and OGT, ChREBP, TXNIP, or NF-κB in diabetic retinas compared to control retinas. 28843855 6 39 theme transferase-mediated 1126:1145 arg1 labelling 1161:1169 terminal deoxynucleotide transferase-mediated dUTP nick-end labelling 1101:1169 terminal deoxynucleotide transferase-mediated dUTP nick-end labelling (TUNEL)-positive ganglion cells 1101:1201 Double immunofluorescence analysis revealed increased co-localization of terminal deoxynucleotide transferase-mediated dUTP nick-end labelling (TUNEL)-positive ganglion cells and OGT, ChREBP, TXNIP, or NF-κB in diabetic retinas compared to control retinas. 28843855 4 40 theme epithelial 791:800 arg1 cells 808:812 retinal pigment epithelial (RPE) cells 775:812 retinal pigment epithelial (RPE) cells 775:812 Western blot analysis showed that levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) and other related proteins such as carbohydrate-responsive element-binding protein (ChREBP) and thioredoxin-interacting protein (TXNIP) were significantly increased, and nuclear factor kappaB (NF-κB) and poly (ADP-ribose) polymerase (PARP) were activated in the diabetic retinas or retinal pigment epithelial (RPE) cells exposed to high glucose compared to controls. 28843855 6 41 theme terminal 1101:1108 arg1 TUNEL 1172:1176 TUNEL 1172:1176 TUNEL 1172:1176 Double immunofluorescence analysis revealed increased co-localization of terminal deoxynucleotide transferase-mediated dUTP nick-end labelling (TUNEL)-positive ganglion cells and OGT, ChREBP, TXNIP, or NF-κB in diabetic retinas compared to control retinas. 28843855 6 41 theme terminal 1101:1108 arg1 labelling 1161:1169 terminal deoxynucleotide transferase-mediated dUTP nick-end labelling 1101:1169 terminal deoxynucleotide transferase-mediated dUTP nick-end labelling (TUNEL)-positive ganglion cells 1101:1201 Double immunofluorescence analysis revealed increased co-localization of terminal deoxynucleotide transferase-mediated dUTP nick-end labelling (TUNEL)-positive ganglion cells and OGT, ChREBP, TXNIP, or NF-κB in diabetic retinas compared to control retinas. 28843855 4 42 theme blot 397:400 arg1 analysis 402:409 Western blot analysis 389:409 Western blot analysis 389:409 Western blot analysis showed that levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) and other related proteins such as carbohydrate-responsive element-binding protein (ChREBP) and thioredoxin-interacting protein (TXNIP) were significantly increased, and nuclear factor kappaB (NF-κB) and poly (ADP-ribose) polymerase (PARP) were activated in the diabetic retinas or retinal pigment epithelial (RPE) cells exposed to high glucose compared to controls. 28843855 7 43 theme cell 1469:1472 arg1 death 1474:1478 more cell death 1464:1478 more cell death 1464:1478 Co-immunoprecipitation analysis showed that interaction between OGT and ChREBP or NF-κB was increased in diabetic retinas compared to control retinas, and this was accompanied by more cell death. 28843855 2 44 theme retinal 260:266 arg1 injury 268:273 retinal injury 260:273 retinal injury in diabetic mice 260:290 Here we investigated how the widely used antidiabetic drug metformin reduces retinal injury in diabetic mice. 28843855 1 45 theme blindness 149:157 arg1 cause 140:144 the major cause 130:144 the major cause of blindness in the developed world 130:180 Retinal degeneration is an early feature of diabetic retinopathy, the major cause of blindness in the developed world. 28843855 1 45 theme blindness 149:157 arg1 feature 97:103 an early feature 88:103 an early feature of diabetic retinopathy 88:127 Retinal degeneration is an early feature of diabetic retinopathy, the major cause of blindness in the developed world. 28843855 6 46 theme ganglion 1188:1195 arg1 cells 1197:1201 terminal deoxynucleotide transferase-mediated dUTP nick-end labelling (TUNEL)-positive ganglion cells 1101:1201 terminal deoxynucleotide transferase-mediated dUTP nick-end labelling (TUNEL)-positive ganglion cells 1101:1201 Double immunofluorescence analysis revealed increased co-localization of terminal deoxynucleotide transferase-mediated dUTP nick-end labelling (TUNEL)-positive ganglion cells and OGT, ChREBP, TXNIP, or NF-κB in diabetic retinas compared to control retinas. 28843855 5 47 contain had 939:941 arg2 levels 950:955 higher levels 943:955 higher levels of those proteins 943:973 More importantly, RPE cells exposed to high glucose and treated with thiamet-G had higher levels of those proteins, demonstrating the role of elevated O-GlcNAcylation. 28843855 5 47 contain had 939:941 arg1 cells 882:886 RPE cells 878:886 RPE cells exposed to high glucose and treated with thiamet-G 878:937 More importantly, RPE cells exposed to high glucose and treated with thiamet-G had higher levels of those proteins, demonstrating the role of elevated O-GlcNAcylation. 28843855 4 48 theme factor 671:676 arg1 kappaB 678:683 nuclear factor kappaB 663:683 nuclear factor kappaB (NF-κB) 663:691 Western blot analysis showed that levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) and other related proteins such as carbohydrate-responsive element-binding protein (ChREBP) and thioredoxin-interacting protein (TXNIP) were significantly increased, and nuclear factor kappaB (NF-κB) and poly (ADP-ribose) polymerase (PARP) were activated in the diabetic retinas or retinal pigment epithelial (RPE) cells exposed to high glucose compared to controls. 28843855 4 48 theme factor 671:676 arg1 NF-κB 686:690 NF-κB 686:690 NF-κB 686:690 Western blot analysis showed that levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) and other related proteins such as carbohydrate-responsive element-binding protein (ChREBP) and thioredoxin-interacting protein (TXNIP) were significantly increased, and nuclear factor kappaB (NF-κB) and poly (ADP-ribose) polymerase (PARP) were activated in the diabetic retinas or retinal pigment epithelial (RPE) cells exposed to high glucose compared to controls. 28843855 4 49 theme high 825:828 arg1 glucose 830:836 high glucose 825:836 high glucose 825:836 Western blot analysis showed that levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) and other related proteins such as carbohydrate-responsive element-binding protein (ChREBP) and thioredoxin-interacting protein (TXNIP) were significantly increased, and nuclear factor kappaB (NF-κB) and poly (ADP-ribose) polymerase (PARP) were activated in the diabetic retinas or retinal pigment epithelial (RPE) cells exposed to high glucose compared to controls. 28843855 7 50 theme control 1419:1425 arg1 retinas 1427:1433 control retinas 1419:1433 control retinas 1419:1433 Co-immunoprecipitation analysis showed that interaction between OGT and ChREBP or NF-κB was increased in diabetic retinas compared to control retinas, and this was accompanied by more cell death. 28843855 7 51 theme Co-immunoprecipitation 1285:1306 arg1 analysis 1308:1315 Co-immunoprecipitation analysis 1285:1315 Co-immunoprecipitation analysis 1285:1315 Co-immunoprecipitation analysis showed that interaction between OGT and ChREBP or NF-κB was increased in diabetic retinas compared to control retinas, and this was accompanied by more cell death. 28843855 3 52 with mice 338:341 arg1 diabetes 379:386 streptozotocin-induced diabetes 356:386 streptozotocin-induced diabetes 356:386 Metformin was orally administered to control mice or mice with streptozotocin-induced diabetes. 28843855 4 53 theme carbohydrate-responsive 528:550 arg1 ChREBP 577:582 ChREBP 577:582 ChREBP 577:582 Western blot analysis showed that levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) and other related proteins such as carbohydrate-responsive element-binding protein (ChREBP) and thioredoxin-interacting protein (TXNIP) were significantly increased, and nuclear factor kappaB (NF-κB) and poly (ADP-ribose) polymerase (PARP) were activated in the diabetic retinas or retinal pigment epithelial (RPE) cells exposed to high glucose compared to controls. 28843855 4 53 theme carbohydrate-responsive 528:550 arg1 TXNIP 622:626 TXNIP 622:626 TXNIP 622:626 Western blot analysis showed that levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) and other related proteins such as carbohydrate-responsive element-binding protein (ChREBP) and thioredoxin-interacting protein (TXNIP) were significantly increased, and nuclear factor kappaB (NF-κB) and poly (ADP-ribose) polymerase (PARP) were activated in the diabetic retinas or retinal pigment epithelial (RPE) cells exposed to high glucose compared to controls. 28843855 4 53 theme carbohydrate-responsive 528:550 arg1 protein 568:574 carbohydrate-responsive element-binding protein 528:574 carbohydrate-responsive element-binding protein (ChREBP) 528:583 Western blot analysis showed that levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) and other related proteins such as carbohydrate-responsive element-binding protein (ChREBP) and thioredoxin-interacting protein (TXNIP) were significantly increased, and nuclear factor kappaB (NF-κB) and poly (ADP-ribose) polymerase (PARP) were activated in the diabetic retinas or retinal pigment epithelial (RPE) cells exposed to high glucose compared to controls. 28843855 9 54 theme OGT 1718:1720 arg1 inhibition 1722:1731 OGT inhibition 1718:1731 OGT inhibition 1718:1731 Our results indicate that OGT inhibition might be one of the mechanisms by which metformin decreases retinal cell death. 28843855 7 55 theme diabetic 1390:1397 arg1 retinas 1399:1405 diabetic retinas 1390:1405 diabetic retinas 1390:1405 Co-immunoprecipitation analysis showed that interaction between OGT and ChREBP or NF-κB was increased in diabetic retinas compared to control retinas, and this was accompanied by more cell death. 28843855 4 56 theme ADP-ribose 703:712 arg1 PARP 727:730 PARP 727:730 PARP 727:730 Western blot analysis showed that levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) and other related proteins such as carbohydrate-responsive element-binding protein (ChREBP) and thioredoxin-interacting protein (TXNIP) were significantly increased, and nuclear factor kappaB (NF-κB) and poly (ADP-ribose) polymerase (PARP) were activated in the diabetic retinas or retinal pigment epithelial (RPE) cells exposed to high glucose compared to controls. 28843855 4 56 theme ADP-ribose 703:712 arg1 polymerase 715:724 poly (ADP-ribose) polymerase 697:724 poly (ADP-ribose) polymerase (PARP) 697:731 Western blot analysis showed that levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) and other related proteins such as carbohydrate-responsive element-binding protein (ChREBP) and thioredoxin-interacting protein (TXNIP) were significantly increased, and nuclear factor kappaB (NF-κB) and poly (ADP-ribose) polymerase (PARP) were activated in the diabetic retinas or retinal pigment epithelial (RPE) cells exposed to high glucose compared to controls. 28843855 5 57 theme O-GlcNAcylation 1011:1025 arg1 role 994:997 the role 990:997 the role of elevated O-GlcNAcylation 990:1025 More importantly, RPE cells exposed to high glucose and treated with thiamet-G had higher levels of those proteins, demonstrating the role of elevated O-GlcNAcylation. 28843855 1 58 theme retinopathy 117:127 arg1 degeneration 72:83 Retinal degeneration 64:83 Retinal degeneration 64:83 Retinal degeneration is an early feature of diabetic retinopathy, the major cause of blindness in the developed world. 28843855 1 58 theme retinopathy 117:127 arg1 cause 140:144 the major cause 130:144 the major cause of blindness in the developed world 130:180 Retinal degeneration is an early feature of diabetic retinopathy, the major cause of blindness in the developed world. 28843855 1 58 theme retinopathy 117:127 arg1 feature 97:103 an early feature 88:103 an early feature of diabetic retinopathy 88:127 Retinal degeneration is an early feature of diabetic retinopathy, the major cause of blindness in the developed world. 28843855 4 59 theme O-linked 433:440 arg1 OGT 488:490 OGT 488:490 OGT 488:490 Western blot analysis showed that levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) and other related proteins such as carbohydrate-responsive element-binding protein (ChREBP) and thioredoxin-interacting protein (TXNIP) were significantly increased, and nuclear factor kappaB (NF-κB) and poly (ADP-ribose) polymerase (PARP) were activated in the diabetic retinas or retinal pigment epithelial (RPE) cells exposed to high glucose compared to controls. 28843855 4 59 theme O-linked 433:440 arg1 transferase 475:485 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase 433:485 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) 433:491 Western blot analysis showed that levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) and other related proteins such as carbohydrate-responsive element-binding protein (ChREBP) and thioredoxin-interacting protein (TXNIP) were significantly increased, and nuclear factor kappaB (NF-κB) and poly (ADP-ribose) polymerase (PARP) were activated in the diabetic retinas or retinal pigment epithelial (RPE) cells exposed to high glucose compared to controls. 28843855 2 60 theme antidiabetic 224:235 arg1 metformin 242:250 the widely used antidiabetic drug metformin 208:250 the widely used antidiabetic drug metformin 208:250 Here we investigated how the widely used antidiabetic drug metformin reduces retinal injury in diabetic mice. 28843855 2 61 from injury 268:273 arg1 mice 287:290 diabetic mice 278:290 diabetic mice 278:290 Here we investigated how the widely used antidiabetic drug metformin reduces retinal injury in diabetic mice. 28843855 4 62 theme other 497:501 arg1 protein 613:619 thioredoxin-interacting protein 589:619 thioredoxin-interacting protein 589:619 Western blot analysis showed that levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) and other related proteins such as carbohydrate-responsive element-binding protein (ChREBP) and thioredoxin-interacting protein (TXNIP) were significantly increased, and nuclear factor kappaB (NF-κB) and poly (ADP-ribose) polymerase (PARP) were activated in the diabetic retinas or retinal pigment epithelial (RPE) cells exposed to high glucose compared to controls. 28843855 4 62 theme other 497:501 arg1 protein 568:574 carbohydrate-responsive element-binding protein 528:574 carbohydrate-responsive element-binding protein (ChREBP) 528:583 Western blot analysis showed that levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) and other related proteins such as carbohydrate-responsive element-binding protein (ChREBP) and thioredoxin-interacting protein (TXNIP) were significantly increased, and nuclear factor kappaB (NF-κB) and poly (ADP-ribose) polymerase (PARP) were activated in the diabetic retinas or retinal pigment epithelial (RPE) cells exposed to high glucose compared to controls. 28843855 4 62 theme other 497:501 arg1 proteins 511:518 other related proteins 497:518 other related proteins such as carbohydrate-responsive element-binding protein (ChREBP) and thioredoxin-interacting protein (TXNIP) 497:627 Western blot analysis showed that levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) and other related proteins such as carbohydrate-responsive element-binding protein (ChREBP) and thioredoxin-interacting protein (TXNIP) were significantly increased, and nuclear factor kappaB (NF-κB) and poly (ADP-ribose) polymerase (PARP) were activated in the diabetic retinas or retinal pigment epithelial (RPE) cells exposed to high glucose compared to controls. 28843855 4 63 link O-linked 433:440 arg1 OGT 488:490 OGT 488:490 OGT 488:490 Western blot analysis showed that levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) and other related proteins such as carbohydrate-responsive element-binding protein (ChREBP) and thioredoxin-interacting protein (TXNIP) were significantly increased, and nuclear factor kappaB (NF-κB) and poly (ADP-ribose) polymerase (PARP) were activated in the diabetic retinas or retinal pigment epithelial (RPE) cells exposed to high glucose compared to controls. 28843855 4 63 link O-linked 433:440 arg1 transferase 475:485 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase 433:485 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) 433:491 Western blot analysis showed that levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) and other related proteins such as carbohydrate-responsive element-binding protein (ChREBP) and thioredoxin-interacting protein (TXNIP) were significantly increased, and nuclear factor kappaB (NF-κB) and poly (ADP-ribose) polymerase (PARP) were activated in the diabetic retinas or retinal pigment epithelial (RPE) cells exposed to high glucose compared to controls. 28843855 4 64 theme proteins 511:518 arg1 levels 423:428 levels 423:428 levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) and other related proteins such as carbohydrate-responsive element-binding protein (ChREBP) and thioredoxin-interacting protein (TXNIP) 423:627 Western blot analysis showed that levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) and other related proteins such as carbohydrate-responsive element-binding protein (ChREBP) and thioredoxin-interacting protein (TXNIP) were significantly increased, and nuclear factor kappaB (NF-κB) and poly (ADP-ribose) polymerase (PARP) were activated in the diabetic retinas or retinal pigment epithelial (RPE) cells exposed to high glucose compared to controls. 28843855 4 65 theme poly 697:700 arg1 PARP 727:730 PARP 727:730 PARP 727:730 Western blot analysis showed that levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) and other related proteins such as carbohydrate-responsive element-binding protein (ChREBP) and thioredoxin-interacting protein (TXNIP) were significantly increased, and nuclear factor kappaB (NF-κB) and poly (ADP-ribose) polymerase (PARP) were activated in the diabetic retinas or retinal pigment epithelial (RPE) cells exposed to high glucose compared to controls. 28843855 4 65 theme poly 697:700 arg1 polymerase 715:724 poly (ADP-ribose) polymerase 697:724 poly (ADP-ribose) polymerase (PARP) 697:731 Western blot analysis showed that levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) and other related proteins such as carbohydrate-responsive element-binding protein (ChREBP) and thioredoxin-interacting protein (TXNIP) were significantly increased, and nuclear factor kappaB (NF-κB) and poly (ADP-ribose) polymerase (PARP) were activated in the diabetic retinas or retinal pigment epithelial (RPE) cells exposed to high glucose compared to controls. 28843855 1 66 theme Retinal 64:70 arg1 degeneration 72:83 Retinal degeneration 64:83 Retinal degeneration 64:83 Retinal degeneration is an early feature of diabetic retinopathy, the major cause of blindness in the developed world. 28843855 1 66 theme Retinal 64:70 arg1 feature 97:103 an early feature 88:103 an early feature of diabetic retinopathy 88:127 Retinal degeneration is an early feature of diabetic retinopathy, the major cause of blindness in the developed world. 28843855 6 67 theme increased 1072:1080 arg1 co-localization 1082:1096 increased co-localization 1072:1096 increased co-localization of terminal deoxynucleotide transferase-mediated dUTP nick-end labelling (TUNEL)-positive ganglion cells 1072:1201 Double immunofluorescence analysis revealed increased co-localization of terminal deoxynucleotide transferase-mediated dUTP nick-end labelling (TUNEL)-positive ganglion cells and OGT, ChREBP, TXNIP, or NF-κB in diabetic retinas compared to control retinas. 28843855 0 68 from death 40:44 arg1 mice 58:61 diabetic mice 49:61 diabetic mice 49:61 Metformin protects against retinal cell death in diabetic mice. 28843855 4 69 theme diabetic 755:762 arg1 retinas 764:770 the diabetic retinas 751:770 the diabetic retinas 751:770 Western blot analysis showed that levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) and other related proteins such as carbohydrate-responsive element-binding protein (ChREBP) and thioredoxin-interacting protein (TXNIP) were significantly increased, and nuclear factor kappaB (NF-κB) and poly (ADP-ribose) polymerase (PARP) were activated in the diabetic retinas or retinal pigment epithelial (RPE) cells exposed to high glucose compared to controls. 28843855 8 70 theme protein 1528:1534 arg1 levels 1536:1541 protein levels 1528:1541 protein levels 1528:1541 Notably, metformin attenuated the increases in protein levels; reduced co-localization of TUNEL-positive ganglion cells and OGT, ChREBP, TXNIP, or NF-κB; and reduced interaction between OGT and ChREBP or NF-κB. 28843855 9 71 theme retinal 1793:1799 arg1 death 1806:1810 retinal cell death 1793:1810 retinal cell death 1793:1810 Our results indicate that OGT inhibition might be one of the mechanisms by which metformin decreases retinal cell death. 28843855 0 72 theme retinal 27:33 arg1 death 40:44 retinal cell death 27:44 retinal cell death in diabetic mice 27:61 Metformin protects against retinal cell death in diabetic mice. 28843855 1 73 theme early 91:95 arg1 degeneration 72:83 Retinal degeneration 64:83 Retinal degeneration 64:83 Retinal degeneration is an early feature of diabetic retinopathy, the major cause of blindness in the developed world. 28843855 1 73 theme early 91:95 arg1 cause 140:144 the major cause 130:144 the major cause of blindness in the developed world 130:180 Retinal degeneration is an early feature of diabetic retinopathy, the major cause of blindness in the developed world. 28843855 1 73 theme early 91:95 arg1 feature 97:103 an early feature 88:103 an early feature of diabetic retinopathy 88:127 Retinal degeneration is an early feature of diabetic retinopathy, the major cause of blindness in the developed world. 28843855 6 74 theme Double 1028:1033 arg1 analysis 1054:1061 Double immunofluorescence analysis 1028:1061 Double immunofluorescence analysis 1028:1061 Double immunofluorescence analysis revealed increased co-localization of terminal deoxynucleotide transferase-mediated dUTP nick-end labelling (TUNEL)-positive ganglion cells and OGT, ChREBP, TXNIP, or NF-κB in diabetic retinas compared to control retinas. 28843855 3 75 theme streptozotocin-induced 356:377 arg1 diabetes 379:386 streptozotocin-induced diabetes 356:386 streptozotocin-induced diabetes 356:386 Metformin was orally administered to control mice or mice with streptozotocin-induced diabetes. 28843855 8 76 theme ganglion 1586:1593 arg1 cells 1595:1599 TUNEL-positive ganglion cells 1571:1599 TUNEL-positive ganglion cells 1571:1599 Notably, metformin attenuated the increases in protein levels; reduced co-localization of TUNEL-positive ganglion cells and OGT, ChREBP, TXNIP, or NF-κB; and reduced interaction between OGT and ChREBP or NF-κB. 28843855 8 77 from interaction 1647:1657 arg1 levels 1536:1541 protein levels 1528:1541 protein levels 1528:1541 Notably, metformin attenuated the increases in protein levels; reduced co-localization of TUNEL-positive ganglion cells and OGT, ChREBP, TXNIP, or NF-κB; and reduced interaction between OGT and ChREBP or NF-κB. 28843855 0 78 theme diabetic 49:56 arg1 mice 58:61 diabetic mice 49:61 diabetic mice 49:61 Metformin protects against retinal cell death in diabetic mice. 28843855 8 79 theme reduced 1544:1550 arg1 co-localization 1552:1566 reduced co-localization 1544:1566 reduced co-localization of TUNEL-positive ganglion cells and OGT, ChREBP, TXNIP, or NF-κB 1544:1632 Notably, metformin attenuated the increases in protein levels; reduced co-localization of TUNEL-positive ganglion cells and OGT, ChREBP, TXNIP, or NF-κB; and reduced interaction between OGT and ChREBP or NF-κB. 28843855 6 80 theme labelling 1161:1169 arg1 cells 1197:1201 terminal deoxynucleotide transferase-mediated dUTP nick-end labelling (TUNEL)-positive ganglion cells 1101:1201 terminal deoxynucleotide transferase-mediated dUTP nick-end labelling (TUNEL)-positive ganglion cells 1101:1201 Double immunofluorescence analysis revealed increased co-localization of terminal deoxynucleotide transferase-mediated dUTP nick-end labelling (TUNEL)-positive ganglion cells and OGT, ChREBP, TXNIP, or NF-κB in diabetic retinas compared to control retinas. 28843855 4 81 theme element-binding 552:566 arg1 ChREBP 577:582 ChREBP 577:582 ChREBP 577:582 Western blot analysis showed that levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) and other related proteins such as carbohydrate-responsive element-binding protein (ChREBP) and thioredoxin-interacting protein (TXNIP) were significantly increased, and nuclear factor kappaB (NF-κB) and poly (ADP-ribose) polymerase (PARP) were activated in the diabetic retinas or retinal pigment epithelial (RPE) cells exposed to high glucose compared to controls. 28843855 4 81 theme element-binding 552:566 arg1 TXNIP 622:626 TXNIP 622:626 TXNIP 622:626 Western blot analysis showed that levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) and other related proteins such as carbohydrate-responsive element-binding protein (ChREBP) and thioredoxin-interacting protein (TXNIP) were significantly increased, and nuclear factor kappaB (NF-κB) and poly (ADP-ribose) polymerase (PARP) were activated in the diabetic retinas or retinal pigment epithelial (RPE) cells exposed to high glucose compared to controls. 28843855 4 81 theme element-binding 552:566 arg1 protein 568:574 carbohydrate-responsive element-binding protein 528:574 carbohydrate-responsive element-binding protein (ChREBP) 528:583 Western blot analysis showed that levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) and other related proteins such as carbohydrate-responsive element-binding protein (ChREBP) and thioredoxin-interacting protein (TXNIP) were significantly increased, and nuclear factor kappaB (NF-κB) and poly (ADP-ribose) polymerase (PARP) were activated in the diabetic retinas or retinal pigment epithelial (RPE) cells exposed to high glucose compared to controls. 28843855 6 82 theme dUTP 1147:1150 arg1 TUNEL 1172:1176 TUNEL 1172:1176 TUNEL 1172:1176 Double immunofluorescence analysis revealed increased co-localization of terminal deoxynucleotide transferase-mediated dUTP nick-end labelling (TUNEL)-positive ganglion cells and OGT, ChREBP, TXNIP, or NF-κB in diabetic retinas compared to control retinas. 28843855 6 82 theme dUTP 1147:1150 arg1 labelling 1161:1169 terminal deoxynucleotide transferase-mediated dUTP nick-end labelling 1101:1169 terminal deoxynucleotide transferase-mediated dUTP nick-end labelling (TUNEL)-positive ganglion cells 1101:1201 Double immunofluorescence analysis revealed increased co-localization of terminal deoxynucleotide transferase-mediated dUTP nick-end labelling (TUNEL)-positive ganglion cells and OGT, ChREBP, TXNIP, or NF-κB in diabetic retinas compared to control retinas. 28843855 5 83 theme proteins 966:973 arg1 levels 950:955 higher levels 943:955 higher levels of those proteins 943:973 More importantly, RPE cells exposed to high glucose and treated with thiamet-G had higher levels of those proteins, demonstrating the role of elevated O-GlcNAcylation. 28843855 6 84 theme deoxynucleotide 1110:1124 arg1 TUNEL 1172:1176 TUNEL 1172:1176 TUNEL 1172:1176 Double immunofluorescence analysis revealed increased co-localization of terminal deoxynucleotide transferase-mediated dUTP nick-end labelling (TUNEL)-positive ganglion cells and OGT, ChREBP, TXNIP, or NF-κB in diabetic retinas compared to control retinas. 28843855 6 84 theme deoxynucleotide 1110:1124 arg1 labelling 1161:1169 terminal deoxynucleotide transferase-mediated dUTP nick-end labelling 1101:1169 terminal deoxynucleotide transferase-mediated dUTP nick-end labelling (TUNEL)-positive ganglion cells 1101:1201 Double immunofluorescence analysis revealed increased co-localization of terminal deoxynucleotide transferase-mediated dUTP nick-end labelling (TUNEL)-positive ganglion cells and OGT, ChREBP, TXNIP, or NF-κB in diabetic retinas compared to control retinas. 28843855 4 85 theme pigment 783:789 arg1 cells 808:812 retinal pigment epithelial (RPE) cells 775:812 retinal pigment epithelial (RPE) cells 775:812 Western blot analysis showed that levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) and other related proteins such as carbohydrate-responsive element-binding protein (ChREBP) and thioredoxin-interacting protein (TXNIP) were significantly increased, and nuclear factor kappaB (NF-κB) and poly (ADP-ribose) polymerase (PARP) were activated in the diabetic retinas or retinal pigment epithelial (RPE) cells exposed to high glucose compared to controls. 28300646 6 0 theme comparative 901:911 arg1 study 913:917 a comparative study 899:917 a comparative study 899:917 Here, a comparative study was carried out into TRAK-mediated mitochondrial mobility in axons and dendrites of hippocampal and cortical neurons during maturation in vitro using a shRNA gene knockdown approach. 28300646 7 1 theme dendritic 1232:1240 arg1 transport 1242:1250 dendritic transport 1232:1250 dendritic transport 1232:1250 It was found that in mature hippocampal and cortical neurons, TRAK1 predominantly mediates axonal mitochondrial transport whereas dendritic transport is mediated via TRAK2. 28300646 0 2 from changes 14:20 arg1 transport 53:61 trak-mediated mitochondrial transport 25:61 trak-mediated mitochondrial transport in neurons 25:72 Developmental changes in trak-mediated mitochondrial transport in neurons. 28300646 6 3 theme knockdown 1082:1090 arg1 approach 1092:1099 a shRNA gene knockdown approach 1069:1099 a shRNA gene knockdown approach 1069:1099 Here, a comparative study was carried out into TRAK-mediated mitochondrial mobility in axons and dendrites of hippocampal and cortical neurons during maturation in vitro using a shRNA gene knockdown approach. 28300646 7 4 theme mitochondrial 1200:1212 arg1 transport 1214:1222 axonal mitochondrial transport 1193:1222 axonal mitochondrial transport 1193:1222 It was found that in mature hippocampal and cortical neurons, TRAK1 predominantly mediates axonal mitochondrial transport whereas dendritic transport is mediated via TRAK2. 28300646 4 5 theme hippocampal 590:600 arg1 neurons 602:608 hippocampal neurons 590:608 hippocampal neurons 590:608 A recent report suggested that TRAK1 preferentially controls mitochondrial transport in axons of hippocampal neurons whereas TRAK2 controls mitochondrial transport in dendrites. 28300646 7 6 theme axonal 1193:1198 arg1 transport 1214:1222 axonal mitochondrial transport 1193:1222 axonal mitochondrial transport 1193:1222 It was found that in mature hippocampal and cortical neurons, TRAK1 predominantly mediates axonal mitochondrial transport whereas dendritic transport is mediated via TRAK2. 28300646 2 7 theme acceptor 278:285 arg1 protein 287:293 a TRAK acceptor protein 271:293 a TRAK acceptor protein in the mitochondrial outer membrane 271:329 They link mitochondria to kinesin motor proteins via a TRAK acceptor protein in the mitochondrial outer membrane, the Rho GTPase, Miro. 28300646 2 7 theme acceptor 278:285 arg1 Miro 348:351 Miro 348:351 Miro 348:351 They link mitochondria to kinesin motor proteins via a TRAK acceptor protein in the mitochondrial outer membrane, the Rho GTPase, Miro. 28300646 2 7 theme acceptor 278:285 arg1 GTPase 340:345 the Rho GTPase 332:345 the Rho GTPase 332:345 They link mitochondria to kinesin motor proteins via a TRAK acceptor protein in the mitochondrial outer membrane, the Rho GTPase, Miro. 28300646 8 8 theme mitochondrial 1343:1355 arg1 transport 1357:1365 mitochondrial transport 1343:1365 mitochondrial transport in both axons and dendrites in both neuronal types 1343:1416 In young, maturing neurons, TRAK1 and TRAK2 contribute similarly in mitochondrial transport in both axons and dendrites in both neuronal types. 28300646 1 9 theme Previous 75:82 arg1 studies 84:90 Previous studies 75:90 Previous studies 75:90 Previous studies established that the kinesin adaptor proteins, TRAK1 and TRAK2, play an important role in mitochondrial transport in neurons. 28300646 6 10 from mobility 968:975 arg1 dendrites 990:998 dendrites 990:998 dendrites 990:998 Here, a comparative study was carried out into TRAK-mediated mitochondrial mobility in axons and dendrites of hippocampal and cortical neurons during maturation in vitro using a shRNA gene knockdown approach. 28300646 6 10 from mobility 968:975 arg1 axons 980:984 axons 980:984 axons 980:984 Here, a comparative study was carried out into TRAK-mediated mitochondrial mobility in axons and dendrites of hippocampal and cortical neurons during maturation in vitro using a shRNA gene knockdown approach. 28300646 2 11 attach link 223:226 arg2 They 218:221 They 218:221 They 218:221 They link mitochondria to kinesin motor proteins via a TRAK acceptor protein in the mitochondrial outer membrane, the Rho GTPase, Miro. 28300646 2 11 attach link 223:226 arg1 proteins 258:265 kinesin motor proteins 244:265 kinesin motor proteins 244:265 They link mitochondria to kinesin motor proteins via a TRAK acceptor protein in the mitochondrial outer membrane, the Rho GTPase, Miro. 28300646 3 12 theme mitochondrial 458:470 arg1 complex 484:490 a quaternary, mitochondrial trafficking complex 444:490 complex 484:490 TRAKs also associate with enzyme, O-linked N-acetylglucosamine transferase (OGT), to form a quaternary, mitochondrial trafficking complex. 28300646 6 13 theme gene 1077:1080 arg1 approach 1092:1099 a shRNA gene knockdown approach 1069:1099 a shRNA gene knockdown approach 1069:1099 Here, a comparative study was carried out into TRAK-mediated mitochondrial mobility in axons and dendrites of hippocampal and cortical neurons during maturation in vitro using a shRNA gene knockdown approach. 28300646 2 14 theme TRAK 273:276 arg1 protein 287:293 a TRAK acceptor protein 271:293 a TRAK acceptor protein in the mitochondrial outer membrane 271:329 They link mitochondria to kinesin motor proteins via a TRAK acceptor protein in the mitochondrial outer membrane, the Rho GTPase, Miro. 28300646 2 14 theme TRAK 273:276 arg1 Miro 348:351 Miro 348:351 Miro 348:351 They link mitochondria to kinesin motor proteins via a TRAK acceptor protein in the mitochondrial outer membrane, the Rho GTPase, Miro. 28300646 2 14 theme TRAK 273:276 arg1 GTPase 340:345 the Rho GTPase 332:345 the Rho GTPase 332:345 They link mitochondria to kinesin motor proteins via a TRAK acceptor protein in the mitochondrial outer membrane, the Rho GTPase, Miro. 28300646 8 15 from transport 1357:1365 arg1 types 1412:1416 both neuronal types 1398:1416 both neuronal types 1398:1416 In young, maturing neurons, TRAK1 and TRAK2 contribute similarly in mitochondrial transport in both axons and dendrites in both neuronal types. 28300646 8 15 from transport 1357:1365 arg1 dendrites 1385:1393 dendrites 1385:1393 dendrites 1385:1393 In young, maturing neurons, TRAK1 and TRAK2 contribute similarly in mitochondrial transport in both axons and dendrites in both neuronal types. 28300646 8 15 from transport 1357:1365 arg1 axons 1375:1379 axons 1375:1379 axons 1375:1379 In young, maturing neurons, TRAK1 and TRAK2 contribute similarly in mitochondrial transport in both axons and dendrites in both neuronal types. 28300646 1 16 theme important 164:172 arg1 role 174:177 an important role 161:177 an important role 161:177 Previous studies established that the kinesin adaptor proteins, TRAK1 and TRAK2, play an important role in mitochondrial transport in neurons. 28300646 7 17 theme hippocampal 1130:1140 arg1 neurons 1155:1161 mature hippocampal and cortical neurons 1123:1161 mature hippocampal and cortical neurons 1123:1161 It was found that in mature hippocampal and cortical neurons, TRAK1 predominantly mediates axonal mitochondrial transport whereas dendritic transport is mediated via TRAK2. 28300646 0 18 from transport 53:61 arg1 neurons 66:72 neurons 66:72 neurons 66:72 Developmental changes in trak-mediated mitochondrial transport in neurons. 28300646 6 19 from maturation 1043:1052 arg1 vitro 1057:1061 vitro 1057:1061 vitro using a shRNA gene knockdown approach 1057:1099 Here, a comparative study was carried out into TRAK-mediated mitochondrial mobility in axons and dendrites of hippocampal and cortical neurons during maturation in vitro using a shRNA gene knockdown approach. 28300646 6 20 theme cortical 1019:1026 arg1 neurons 1028:1034 hippocampal and cortical neurons 1003:1034 hippocampal and cortical neurons during maturation in vitro using a shRNA gene knockdown approach 1003:1099 Here, a comparative study was carried out into TRAK-mediated mitochondrial mobility in axons and dendrites of hippocampal and cortical neurons during maturation in vitro using a shRNA gene knockdown approach. 28300646 6 21 theme shRNA 1071:1075 arg1 approach 1092:1099 a shRNA gene knockdown approach 1069:1099 a shRNA gene knockdown approach 1069:1099 Here, a comparative study was carried out into TRAK-mediated mitochondrial mobility in axons and dendrites of hippocampal and cortical neurons during maturation in vitro using a shRNA gene knockdown approach. 28300646 4 22 from transport 568:576 arg1 axons 581:585 axons 581:585 axons of hippocampal neurons 581:608 A recent report suggested that TRAK1 preferentially controls mitochondrial transport in axons of hippocampal neurons whereas TRAK2 controls mitochondrial transport in dendrites. 28300646 6 23 theme TRAK-mediated 940:952 arg1 mobility 968:975 TRAK-mediated mitochondrial mobility 940:975 TRAK-mediated mitochondrial mobility in axons and dendrites of hippocampal and cortical neurons during maturation in vitro using a shRNA gene knockdown approach 940:1099 Here, a comparative study was carried out into TRAK-mediated mitochondrial mobility in axons and dendrites of hippocampal and cortical neurons during maturation in vitro using a shRNA gene knockdown approach. 28300646 2 24 theme outer 316:320 arg1 membrane 322:329 the mitochondrial outer membrane 298:329 the mitochondrial outer membrane 298:329 They link mitochondria to kinesin motor proteins via a TRAK acceptor protein in the mitochondrial outer membrane, the Rho GTPase, Miro. 28300646 9 25 theme mitochondrial 1471:1483 arg1 transport 1485:1493 mitochondrial transport 1471:1493 mitochondrial transport 1471:1493 These findings demonstrate maturation regulation of mitochondrial transport which is conserved between at least two distinct neuronal subtypes. 28300646 0 26 theme Developmental 0:12 arg1 changes 14:20 Developmental changes 0:20 Developmental changes in trak-mediated mitochondrial transport in neurons 0:72 Developmental changes in trak-mediated mitochondrial transport in neurons. 28300646 7 27 theme cortical 1146:1153 arg1 neurons 1155:1161 mature hippocampal and cortical neurons 1123:1161 mature hippocampal and cortical neurons 1123:1161 It was found that in mature hippocampal and cortical neurons, TRAK1 predominantly mediates axonal mitochondrial transport whereas dendritic transport is mediated via TRAK2. 28300646 2 28 theme mitochondrial 302:314 arg1 membrane 322:329 the mitochondrial outer membrane 298:329 the mitochondrial outer membrane 298:329 They link mitochondria to kinesin motor proteins via a TRAK acceptor protein in the mitochondrial outer membrane, the Rho GTPase, Miro. 28300646 1 29 theme mitochondrial 182:194 arg1 transport 196:204 mitochondrial transport 182:204 mitochondrial transport in neurons 182:215 Previous studies established that the kinesin adaptor proteins, TRAK1 and TRAK2, play an important role in mitochondrial transport in neurons. 28300646 0 30 theme trak-mediated 25:37 arg1 transport 53:61 trak-mediated mitochondrial transport 25:61 trak-mediated mitochondrial transport in neurons 25:72 Developmental changes in trak-mediated mitochondrial transport in neurons. 28300646 1 31 theme kinesin 113:119 arg1 TRAK1 139:143 TRAK1 139:143 TRAK1 139:143 Previous studies established that the kinesin adaptor proteins, TRAK1 and TRAK2, play an important role in mitochondrial transport in neurons. 28300646 1 31 theme kinesin 113:119 arg1 proteins 129:136 the kinesin adaptor proteins 109:136 the kinesin adaptor proteins 109:136 Previous studies established that the kinesin adaptor proteins, TRAK1 and TRAK2, play an important role in mitochondrial transport in neurons. 28300646 1 31 theme kinesin 113:119 arg1 TRAK2 149:153 TRAK2 149:153 TRAK2 149:153 Previous studies established that the kinesin adaptor proteins, TRAK1 and TRAK2, play an important role in mitochondrial transport in neurons. 28300646 8 32 theme young 1278:1282 arg1 neurons 1294:1300 young, maturing neurons 1278:1300 young, maturing neurons 1278:1300 In young, maturing neurons, TRAK1 and TRAK2 contribute similarly in mitochondrial transport in both axons and dendrites in both neuronal types. 28300646 6 33 theme mitochondrial 954:966 arg1 mobility 968:975 TRAK-mediated mitochondrial mobility 940:975 TRAK-mediated mitochondrial mobility in axons and dendrites of hippocampal and cortical neurons during maturation in vitro using a shRNA gene knockdown approach 940:1099 Here, a comparative study was carried out into TRAK-mediated mitochondrial mobility in axons and dendrites of hippocampal and cortical neurons during maturation in vitro using a shRNA gene knockdown approach. 28300646 8 34 dep young 1278:1282 arg1 maturing 1285:1292 maturing 1285:1292 maturing 1285:1292 In young, maturing neurons, TRAK1 and TRAK2 contribute similarly in mitochondrial transport in both axons and dendrites in both neuronal types. 28300646 1 35 theme adaptor 121:127 arg1 TRAK1 139:143 TRAK1 139:143 TRAK1 139:143 Previous studies established that the kinesin adaptor proteins, TRAK1 and TRAK2, play an important role in mitochondrial transport in neurons. 28300646 1 35 theme adaptor 121:127 arg1 proteins 129:136 the kinesin adaptor proteins 109:136 the kinesin adaptor proteins 109:136 Previous studies established that the kinesin adaptor proteins, TRAK1 and TRAK2, play an important role in mitochondrial transport in neurons. 28300646 1 35 theme adaptor 121:127 arg1 TRAK2 149:153 TRAK2 149:153 TRAK2 149:153 Previous studies established that the kinesin adaptor proteins, TRAK1 and TRAK2, play an important role in mitochondrial transport in neurons. 28300646 4 36 from transport 647:655 arg1 dendrites 660:668 dendrites 660:668 dendrites 660:668 A recent report suggested that TRAK1 preferentially controls mitochondrial transport in axons of hippocampal neurons whereas TRAK2 controls mitochondrial transport in dendrites. 28300646 4 37 theme mitochondrial 633:645 arg1 transport 647:655 mitochondrial transport 633:655 mitochondrial transport in dendrites 633:668 A recent report suggested that TRAK1 preferentially controls mitochondrial transport in axons of hippocampal neurons whereas TRAK2 controls mitochondrial transport in dendrites. 28300646 3 38 theme O-linked 388:395 arg1 OGT 430:432 OGT 430:432 OGT 430:432 TRAKs also associate with enzyme, O-linked N-acetylglucosamine transferase (OGT), to form a quaternary, mitochondrial trafficking complex. 28300646 3 38 theme O-linked 388:395 arg1 transferase 417:427 O-linked N-acetylglucosamine transferase 388:427 O-linked N-acetylglucosamine transferase (OGT) 388:433 TRAKs also associate with enzyme, O-linked N-acetylglucosamine transferase (OGT), to form a quaternary, mitochondrial trafficking complex. 28300646 3 38 theme O-linked 388:395 arg1 enzyme 380:385 enzyme 380:385 enzyme 380:385 TRAKs also associate with enzyme, O-linked N-acetylglucosamine transferase (OGT), to form a quaternary, mitochondrial trafficking complex. 28300646 4 39 theme mitochondrial 554:566 arg1 transport 568:576 mitochondrial transport 554:576 mitochondrial transport in axons of hippocampal neurons 554:608 A recent report suggested that TRAK1 preferentially controls mitochondrial transport in axons of hippocampal neurons whereas TRAK2 controls mitochondrial transport in dendrites. 28300646 8 40 theme neuronal 1403:1410 arg1 types 1412:1416 both neuronal types 1398:1416 both neuronal types 1398:1416 In young, maturing neurons, TRAK1 and TRAK2 contribute similarly in mitochondrial transport in both axons and dendrites in both neuronal types. 28300646 9 41 theme transport 1485:1493 arg1 regulation 1457:1466 maturation regulation 1446:1466 maturation regulation of mitochondrial transport which is conserved between at least two distinct neuronal subtypes 1446:1560 These findings demonstrate maturation regulation of mitochondrial transport which is conserved between at least two distinct neuronal subtypes. 28300646 5 42 theme different 833:841 arg1 populations 852:862 different neuronal populations 833:862 different neuronal populations 833:862 However, it is not clear whether the function of any of these proteins is exclusive to axons or dendrites and if their mechanisms of action are conserved between different neuronal populations and also, during maturation. 28300646 0 43 theme mitochondrial 39:51 arg1 transport 53:61 trak-mediated mitochondrial transport 25:61 trak-mediated mitochondrial transport in neurons 25:72 Developmental changes in trak-mediated mitochondrial transport in neurons. 28300646 3 44 theme N-acetylglucosamine 397:415 arg1 OGT 430:432 OGT 430:432 OGT 430:432 TRAKs also associate with enzyme, O-linked N-acetylglucosamine transferase (OGT), to form a quaternary, mitochondrial trafficking complex. 28300646 3 44 theme N-acetylglucosamine 397:415 arg1 transferase 417:427 O-linked N-acetylglucosamine transferase 388:427 O-linked N-acetylglucosamine transferase (OGT) 388:433 TRAKs also associate with enzyme, O-linked N-acetylglucosamine transferase (OGT), to form a quaternary, mitochondrial trafficking complex. 28300646 3 44 theme N-acetylglucosamine 397:415 arg1 enzyme 380:385 enzyme 380:385 enzyme 380:385 TRAKs also associate with enzyme, O-linked N-acetylglucosamine transferase (OGT), to form a quaternary, mitochondrial trafficking complex. 28300646 5 45 theme action 804:809 arg1 mechanisms 790:799 their mechanisms 784:799 their mechanisms of action 784:809 However, it is not clear whether the function of any of these proteins is exclusive to axons or dendrites and if their mechanisms of action are conserved between different neuronal populations and also, during maturation. 28300646 4 46 theme recent 495:500 arg1 report 502:507 A recent report 493:507 A recent report 493:507 A recent report suggested that TRAK1 preferentially controls mitochondrial transport in axons of hippocampal neurons whereas TRAK2 controls mitochondrial transport in dendrites. 28300646 5 47 theme neuronal 843:850 arg1 populations 852:862 different neuronal populations 833:862 different neuronal populations 833:862 However, it is not clear whether the function of any of these proteins is exclusive to axons or dendrites and if their mechanisms of action are conserved between different neuronal populations and also, during maturation. 28300646 7 48 theme mature 1123:1128 arg1 neurons 1155:1161 mature hippocampal and cortical neurons 1123:1161 mature hippocampal and cortical neurons 1123:1161 It was found that in mature hippocampal and cortical neurons, TRAK1 predominantly mediates axonal mitochondrial transport whereas dendritic transport is mediated via TRAK2. 28300646 3 49 link O-linked 388:395 arg1 OGT 430:432 OGT 430:432 OGT 430:432 TRAKs also associate with enzyme, O-linked N-acetylglucosamine transferase (OGT), to form a quaternary, mitochondrial trafficking complex. 28300646 3 49 link O-linked 388:395 arg1 transferase 417:427 O-linked N-acetylglucosamine transferase 388:427 O-linked N-acetylglucosamine transferase (OGT) 388:433 TRAKs also associate with enzyme, O-linked N-acetylglucosamine transferase (OGT), to form a quaternary, mitochondrial trafficking complex. 28300646 3 49 link O-linked 388:395 arg1 enzyme 380:385 enzyme 380:385 enzyme 380:385 TRAKs also associate with enzyme, O-linked N-acetylglucosamine transferase (OGT), to form a quaternary, mitochondrial trafficking complex. 28300646 2 50 theme Rho 336:338 arg1 protein 287:293 a TRAK acceptor protein 271:293 a TRAK acceptor protein in the mitochondrial outer membrane 271:329 They link mitochondria to kinesin motor proteins via a TRAK acceptor protein in the mitochondrial outer membrane, the Rho GTPase, Miro. 28300646 2 50 theme Rho 336:338 arg1 GTPase 340:345 the Rho GTPase 332:345 the Rho GTPase 332:345 They link mitochondria to kinesin motor proteins via a TRAK acceptor protein in the mitochondrial outer membrane, the Rho GTPase, Miro. 28300646 5 51 theme any 720:722 arg1 function 708:715 the function 704:715 the function of any of these proteins 704:740 However, it is not clear whether the function of any of these proteins is exclusive to axons or dendrites and if their mechanisms of action are conserved between different neuronal populations and also, during maturation. 28300646 5 51 theme any 720:722 arg1 exclusive 745:753 exclusive 745:753 exclusive 745:753 However, it is not clear whether the function of any of these proteins is exclusive to axons or dendrites and if their mechanisms of action are conserved between different neuronal populations and also, during maturation. 28300646 1 52 from transport 196:204 arg1 neurons 209:215 neurons 209:215 neurons 209:215 Previous studies established that the kinesin adaptor proteins, TRAK1 and TRAK2, play an important role in mitochondrial transport in neurons. 28300646 3 53 theme trafficking 472:482 arg1 complex 484:490 a quaternary, mitochondrial trafficking complex 444:490 complex 484:490 TRAKs also associate with enzyme, O-linked N-acetylglucosamine transferase (OGT), to form a quaternary, mitochondrial trafficking complex. 28300646 9 54 theme maturation 1446:1455 arg1 regulation 1457:1466 maturation regulation 1446:1466 maturation regulation of mitochondrial transport which is conserved between at least two distinct neuronal subtypes 1446:1560 These findings demonstrate maturation regulation of mitochondrial transport which is conserved between at least two distinct neuronal subtypes. 28300646 3 55 theme quaternary 446:455 arg1 complex 484:490 a quaternary, mitochondrial trafficking complex 444:490 complex 484:490 TRAKs also associate with enzyme, O-linked N-acetylglucosamine transferase (OGT), to form a quaternary, mitochondrial trafficking complex. 28300646 6 56 theme neurons 1028:1034 arg1 mobility 968:975 TRAK-mediated mitochondrial mobility 940:975 TRAK-mediated mitochondrial mobility in axons and dendrites of hippocampal and cortical neurons during maturation in vitro using a shRNA gene knockdown approach 940:1099 Here, a comparative study was carried out into TRAK-mediated mitochondrial mobility in axons and dendrites of hippocampal and cortical neurons during maturation in vitro using a shRNA gene knockdown approach. 28300646 9 57 theme distinct 1535:1542 arg1 subtypes 1553:1560 at least two distinct neuronal subtypes 1522:1560 at least two distinct neuronal subtypes 1522:1560 These findings demonstrate maturation regulation of mitochondrial transport which is conserved between at least two distinct neuronal subtypes. 28300646 2 58 from protein 287:293 arg1 membrane 322:329 the mitochondrial outer membrane 298:329 the mitochondrial outer membrane 298:329 They link mitochondria to kinesin motor proteins via a TRAK acceptor protein in the mitochondrial outer membrane, the Rho GTPase, Miro. 28300646 4 59 theme neurons 602:608 arg1 axons 581:585 axons 581:585 axons of hippocampal neurons 581:608 A recent report suggested that TRAK1 preferentially controls mitochondrial transport in axons of hippocampal neurons whereas TRAK2 controls mitochondrial transport in dendrites. 28300646 2 60 theme motor 252:256 arg1 proteins 258:265 kinesin motor proteins 244:265 kinesin motor proteins 244:265 They link mitochondria to kinesin motor proteins via a TRAK acceptor protein in the mitochondrial outer membrane, the Rho GTPase, Miro. 28300646 9 61 theme neuronal 1544:1551 arg1 subtypes 1553:1560 at least two distinct neuronal subtypes 1522:1560 at least two distinct neuronal subtypes 1522:1560 These findings demonstrate maturation regulation of mitochondrial transport which is conserved between at least two distinct neuronal subtypes. 28300646 2 62 theme kinesin 244:250 arg1 proteins 258:265 kinesin motor proteins 244:265 kinesin motor proteins 244:265 They link mitochondria to kinesin motor proteins via a TRAK acceptor protein in the mitochondrial outer membrane, the Rho GTPase, Miro. 28300646 6 63 theme hippocampal 1003:1013 arg1 neurons 1028:1034 hippocampal and cortical neurons 1003:1034 hippocampal and cortical neurons during maturation in vitro using a shRNA gene knockdown approach 1003:1099 Here, a comparative study was carried out into TRAK-mediated mitochondrial mobility in axons and dendrites of hippocampal and cortical neurons during maturation in vitro using a shRNA gene knockdown approach. 28280036 4 0 theme O-GlcNAc 681:688 arg1 transferase 690:700 O-GlcNAc transferase 681:700 the O-GlcNAc transferase (OGT) 677:706 We further found that cullin 3 (CUL3), a cullin family E3 ubiquitin ligase, down-regulates the expression of the O-GlcNAc transferase (OGT) and inhibits STAT3 O-GlcNAcylation. 28280036 4 0 theme O-GlcNAc 681:688 arg1 OGT 703:705 OGT 703:705 OGT 703:705 We further found that cullin 3 (CUL3), a cullin family E3 ubiquitin ligase, down-regulates the expression of the O-GlcNAc transferase (OGT) and inhibits STAT3 O-GlcNAcylation. 28280036 5 1 theme E2-related 823:832 arg1 Nrf2 844:847 Nrf2 844:847 Nrf2 844:847 The inhibitory effect of CUL3 on OGT expression is dependent on nuclear factor E2-related factor-2 (Nrf2), which binds to the Ogt promoter region and increases gene transcription. 28280036 5 1 theme E2-related 823:832 arg1 factor-2 834:841 nuclear factor E2-related factor-2 808:841 nuclear factor E2-related factor-2 (Nrf2) 808:848 The inhibitory effect of CUL3 on OGT expression is dependent on nuclear factor E2-related factor-2 (Nrf2), which binds to the Ogt promoter region and increases gene transcription. 28280036 5 2 theme Ogt 870:872 arg1 region 883:888 the Ogt promoter region 866:888 the Ogt promoter region 866:888 The inhibitory effect of CUL3 on OGT expression is dependent on nuclear factor E2-related factor-2 (Nrf2), which binds to the Ogt promoter region and increases gene transcription. 28280036 5 3 theme CUL3 769:772 arg1 effect 759:764 The inhibitory effect 744:764 The inhibitory effect of CUL3 on OGT expression 744:790 The inhibitory effect of CUL3 on OGT expression is dependent on nuclear factor E2-related factor-2 (Nrf2), which binds to the Ogt promoter region and increases gene transcription. 28280036 5 3 theme CUL3 769:772 arg1 dependent 795:803 dependent 795:803 dependent 795:803 The inhibitory effect of CUL3 on OGT expression is dependent on nuclear factor E2-related factor-2 (Nrf2), which binds to the Ogt promoter region and increases gene transcription. 28280036 3 4 from β-N-acetylglucosamine 426:446 arg1 threonine 462:470 threonine 717 462:474 threonine 717 (T717) 462:481 Here, we demonstrate that modification of STAT3 with O-linked β-N-acetylglucosamine (O-GlcNAc) on threonine 717 (T717) negatively regulates its phosphorylation and targets gene expression in macrophages. 28280036 3 4 from β-N-acetylglucosamine 426:446 arg1 T717 477:480 T717 477:480 T717 477:480 Here, we demonstrate that modification of STAT3 with O-linked β-N-acetylglucosamine (O-GlcNAc) on threonine 717 (T717) negatively regulates its phosphorylation and targets gene expression in macrophages. 28280036 4 5 theme transferase 690:700 arg1 expression 663:672 the expression 659:672 the expression of the O-GlcNAc transferase (OGT) 659:706 We further found that cullin 3 (CUL3), a cullin family E3 ubiquitin ligase, down-regulates the expression of the O-GlcNAc transferase (OGT) and inhibits STAT3 O-GlcNAcylation. 28280036 0 6 theme intestinal 106:115 arg1 inflammation 117:128 intestinal inflammation 106:128 intestinal inflammation 106:128 Myeloid-derived cullin 3 promotes STAT3 phosphorylation by inhibiting OGT expression and protects against intestinal inflammation. 28280036 2 7 theme STAT3 302:306 arg1 phosphorylation 308:322 STAT3 phosphorylation 302:322 STAT3 phosphorylation 302:322 However, the molecular mechanism that modulates STAT3 phosphorylation and activation is not fully understood. 28280036 6 8 theme STAT3 966:970 arg1 phosphorylation 972:986 defective STAT3 phosphorylation 956:986 defective STAT3 phosphorylation 956:986 Myeloid deletion of Cul3 led to defective STAT3 phosphorylation in colon macrophages, which was accompanied by exacerbated colonic inflammation and inflammation-driven tumorigenesis. 28280036 7 9 theme immunometabolism 1253:1268 arg1 importance 1239:1248 the importance 1235:1248 the importance of immunometabolism on colonic inflammation and tumorigenesis 1235:1310 Thus, this study identifies a new form of posttranslational modification of STAT3, modulating its phosphorylation, and suggests the importance of immunometabolism on colonic inflammation and tumorigenesis. 28280036 6 10 theme colon 991:995 arg1 macrophages 997:1007 colon macrophages 991:1007 colon macrophages 991:1007 Myeloid deletion of Cul3 led to defective STAT3 phosphorylation in colon macrophages, which was accompanied by exacerbated colonic inflammation and inflammation-driven tumorigenesis. 28280036 3 11 from expression 541:550 arg1 macrophages 555:565 macrophages 555:565 macrophages 555:565 Here, we demonstrate that modification of STAT3 with O-linked β-N-acetylglucosamine (O-GlcNAc) on threonine 717 (T717) negatively regulates its phosphorylation and targets gene expression in macrophages. 28280036 6 12 theme inflammation-driven 1072:1090 arg1 tumorigenesis 1092:1104 inflammation-driven tumorigenesis 1072:1104 inflammation-driven tumorigenesis 1072:1104 Myeloid deletion of Cul3 led to defective STAT3 phosphorylation in colon macrophages, which was accompanied by exacerbated colonic inflammation and inflammation-driven tumorigenesis. 28280036 6 13 theme defective 956:964 arg1 phosphorylation 972:986 defective STAT3 phosphorylation 956:986 defective STAT3 phosphorylation 956:986 Myeloid deletion of Cul3 led to defective STAT3 phosphorylation in colon macrophages, which was accompanied by exacerbated colonic inflammation and inflammation-driven tumorigenesis. 28280036 0 14 theme Myeloid-derived 0:14 arg1 cullin 16:21 Myeloid-derived cullin 3 0:23 Myeloid-derived cullin 3 0:23 Myeloid-derived cullin 3 promotes STAT3 phosphorylation by inhibiting OGT expression and protects against intestinal inflammation. 28280036 7 15 theme STAT3 1183:1187 arg1 modification 1167:1178 posttranslational modification 1149:1178 posttranslational modification of STAT3 1149:1187 Thus, this study identifies a new form of posttranslational modification of STAT3, modulating its phosphorylation, and suggests the importance of immunometabolism on colonic inflammation and tumorigenesis. 28280036 7 16 theme colonic 1273:1279 arg1 inflammation 1281:1292 colonic inflammation 1273:1292 colonic inflammation 1273:1292 Thus, this study identifies a new form of posttranslational modification of STAT3, modulating its phosphorylation, and suggests the importance of immunometabolism on colonic inflammation and tumorigenesis. 28280036 6 17 theme Cul3 944:947 arg1 deletion 932:939 Myeloid deletion 924:939 Myeloid deletion of Cul3 924:947 Myeloid deletion of Cul3 led to defective STAT3 phosphorylation in colon macrophages, which was accompanied by exacerbated colonic inflammation and inflammation-driven tumorigenesis. 28280036 3 18 theme STAT3 406:410 arg1 modification 390:401 modification 390:401 modification of STAT3 with O-linked β-N-acetylglucosamine (O-GlcNAc) on threonine 717 (T717) 390:481 Here, we demonstrate that modification of STAT3 with O-linked β-N-acetylglucosamine (O-GlcNAc) on threonine 717 (T717) negatively regulates its phosphorylation and targets gene expression in macrophages. 28280036 7 19 theme posttranslational 1149:1165 arg1 modification 1167:1178 posttranslational modification 1149:1178 posttranslational modification of STAT3 1149:1187 Thus, this study identifies a new form of posttranslational modification of STAT3, modulating its phosphorylation, and suggests the importance of immunometabolism on colonic inflammation and tumorigenesis. 28280036 6 20 from phosphorylation 972:986 arg1 macrophages 997:1007 colon macrophages 991:1007 colon macrophages 991:1007 Myeloid deletion of Cul3 led to defective STAT3 phosphorylation in colon macrophages, which was accompanied by exacerbated colonic inflammation and inflammation-driven tumorigenesis. 28280036 6 21 theme exacerbated 1035:1045 arg1 inflammation 1055:1066 exacerbated colonic inflammation 1035:1066 exacerbated colonic inflammation 1035:1066 Myeloid deletion of Cul3 led to defective STAT3 phosphorylation in colon macrophages, which was accompanied by exacerbated colonic inflammation and inflammation-driven tumorigenesis. 28280036 4 22 theme STAT3 721:725 arg1 O-GlcNAcylation 727:741 STAT3 O-GlcNAcylation 721:741 STAT3 O-GlcNAcylation 721:741 We further found that cullin 3 (CUL3), a cullin family E3 ubiquitin ligase, down-regulates the expression of the O-GlcNAc transferase (OGT) and inhibits STAT3 O-GlcNAcylation. 28280036 6 23 theme colonic 1047:1053 arg1 inflammation 1055:1066 exacerbated colonic inflammation 1035:1066 exacerbated colonic inflammation 1035:1066 Myeloid deletion of Cul3 led to defective STAT3 phosphorylation in colon macrophages, which was accompanied by exacerbated colonic inflammation and inflammation-driven tumorigenesis. 28280036 5 24 theme nuclear 808:814 arg1 Nrf2 844:847 Nrf2 844:847 Nrf2 844:847 The inhibitory effect of CUL3 on OGT expression is dependent on nuclear factor E2-related factor-2 (Nrf2), which binds to the Ogt promoter region and increases gene transcription. 28280036 5 24 theme nuclear 808:814 arg1 factor-2 834:841 nuclear factor E2-related factor-2 808:841 nuclear factor E2-related factor-2 (Nrf2) 808:848 The inhibitory effect of CUL3 on OGT expression is dependent on nuclear factor E2-related factor-2 (Nrf2), which binds to the Ogt promoter region and increases gene transcription. 28280036 0 25 link Myeloid-derived 0:14 arg1 cullin 16:21 Myeloid-derived cullin 3 0:23 Myeloid-derived cullin 3 0:23 Myeloid-derived cullin 3 promotes STAT3 phosphorylation by inhibiting OGT expression and protects against intestinal inflammation. 28280036 1 26 theme key 195:197 arg1 mediator 199:206 a key mediator 193:206 a key mediator of intestinal inflammation and tumorigenesis 193:251 Signal transducer and activator of transcription 3 (STAT3) is a key mediator of intestinal inflammation and tumorigenesis. 28280036 1 26 theme key 195:197 arg1 activator 153:161 activator 153:161 activator 153:161 Signal transducer and activator of transcription 3 (STAT3) is a key mediator of intestinal inflammation and tumorigenesis. 28280036 1 26 theme key 195:197 arg1 transducer 138:147 Signal transducer 131:147 Signal transducer 131:147 Signal transducer and activator of transcription 3 (STAT3) is a key mediator of intestinal inflammation and tumorigenesis. 28280036 3 27 with modification 390:401 arg1 O-GlcNAc 449:456 O-GlcNAc 449:456 O-GlcNAc 449:456 Here, we demonstrate that modification of STAT3 with O-linked β-N-acetylglucosamine (O-GlcNAc) on threonine 717 (T717) negatively regulates its phosphorylation and targets gene expression in macrophages. 28280036 3 27 with modification 390:401 arg1 β-N-acetylglucosamine 426:446 O-linked β-N-acetylglucosamine 417:446 O-linked β-N-acetylglucosamine (O-GlcNAc) on threonine 717 (T717) 417:481 Here, we demonstrate that modification of STAT3 with O-linked β-N-acetylglucosamine (O-GlcNAc) on threonine 717 (T717) negatively regulates its phosphorylation and targets gene expression in macrophages. 28280036 4 28 theme cullin 590:595 arg1 CUL3 600:603 cullin 3 (CUL3) 590:604 cullin 3 (CUL3) 590:604 We further found that cullin 3 (CUL3), a cullin family E3 ubiquitin ligase, down-regulates the expression of the O-GlcNAc transferase (OGT) and inhibits STAT3 O-GlcNAcylation. 28280036 4 28 theme cullin 590:595 arg1 ligase 636:641 a cullin family E3 ubiquitin ligase 607:641 a cullin family E3 ubiquitin ligase 607:641 We further found that cullin 3 (CUL3), a cullin family E3 ubiquitin ligase, down-regulates the expression of the O-GlcNAc transferase (OGT) and inhibits STAT3 O-GlcNAcylation. 28280036 7 29 from importance 1239:1248 arg1 tumorigenesis 1298:1310 tumorigenesis 1298:1310 tumorigenesis 1298:1310 Thus, this study identifies a new form of posttranslational modification of STAT3, modulating its phosphorylation, and suggests the importance of immunometabolism on colonic inflammation and tumorigenesis. 28280036 7 29 from importance 1239:1248 arg1 inflammation 1281:1292 colonic inflammation 1273:1292 colonic inflammation 1273:1292 Thus, this study identifies a new form of posttranslational modification of STAT3, modulating its phosphorylation, and suggests the importance of immunometabolism on colonic inflammation and tumorigenesis. 28280036 5 30 theme promoter 874:881 arg1 region 883:888 the Ogt promoter region 866:888 the Ogt promoter region 866:888 The inhibitory effect of CUL3 on OGT expression is dependent on nuclear factor E2-related factor-2 (Nrf2), which binds to the Ogt promoter region and increases gene transcription. 28280036 4 31 theme E3 623:624 arg1 ligase 636:641 a cullin family E3 ubiquitin ligase 607:641 a cullin family E3 ubiquitin ligase 607:641 We further found that cullin 3 (CUL3), a cullin family E3 ubiquitin ligase, down-regulates the expression of the O-GlcNAc transferase (OGT) and inhibits STAT3 O-GlcNAcylation. 28280036 4 31 theme E3 623:624 arg1 CUL3 600:603 cullin 3 (CUL3) 590:604 cullin 3 (CUL3) 590:604 We further found that cullin 3 (CUL3), a cullin family E3 ubiquitin ligase, down-regulates the expression of the O-GlcNAc transferase (OGT) and inhibits STAT3 O-GlcNAcylation. 28280036 0 32 theme STAT3 34:38 arg1 phosphorylation 40:54 STAT3 phosphorylation 34:54 STAT3 phosphorylation 34:54 Myeloid-derived cullin 3 promotes STAT3 phosphorylation by inhibiting OGT expression and protects against intestinal inflammation. 28280036 5 33 theme OGT 777:779 arg1 expression 781:790 OGT expression 777:790 OGT expression 777:790 The inhibitory effect of CUL3 on OGT expression is dependent on nuclear factor E2-related factor-2 (Nrf2), which binds to the Ogt promoter region and increases gene transcription. 28280036 3 34 link O-linked 417:424 arg1 O-GlcNAc 449:456 O-GlcNAc 449:456 O-GlcNAc 449:456 Here, we demonstrate that modification of STAT3 with O-linked β-N-acetylglucosamine (O-GlcNAc) on threonine 717 (T717) negatively regulates its phosphorylation and targets gene expression in macrophages. 28280036 3 34 link O-linked 417:424 arg1 β-N-acetylglucosamine 426:446 O-linked β-N-acetylglucosamine 417:446 O-linked β-N-acetylglucosamine (O-GlcNAc) on threonine 717 (T717) 417:481 Here, we demonstrate that modification of STAT3 with O-linked β-N-acetylglucosamine (O-GlcNAc) on threonine 717 (T717) negatively regulates its phosphorylation and targets gene expression in macrophages. 28280036 1 35 theme intestinal 211:220 arg1 inflammation 222:233 inflammation 222:233 inflammation 222:233 Signal transducer and activator of transcription 3 (STAT3) is a key mediator of intestinal inflammation and tumorigenesis. 28280036 7 36 theme new 1137:1139 arg1 form 1141:1144 a new form 1135:1144 a new form 1135:1144 Thus, this study identifies a new form of posttranslational modification of STAT3, modulating its phosphorylation, and suggests the importance of immunometabolism on colonic inflammation and tumorigenesis. 28280036 6 37 theme Myeloid 924:930 arg1 deletion 932:939 Myeloid deletion 924:939 Myeloid deletion of Cul3 924:947 Myeloid deletion of Cul3 led to defective STAT3 phosphorylation in colon macrophages, which was accompanied by exacerbated colonic inflammation and inflammation-driven tumorigenesis. 28280036 1 38 theme Signal 131:136 arg1 mediator 199:206 a key mediator 193:206 a key mediator of intestinal inflammation and tumorigenesis 193:251 Signal transducer and activator of transcription 3 (STAT3) is a key mediator of intestinal inflammation and tumorigenesis. 28280036 1 38 theme Signal 131:136 arg1 STAT3 183:187 STAT3 183:187 STAT3 183:187 Signal transducer and activator of transcription 3 (STAT3) is a key mediator of intestinal inflammation and tumorigenesis. 28280036 1 38 theme Signal 131:136 arg1 activator 153:161 activator 153:161 activator 153:161 Signal transducer and activator of transcription 3 (STAT3) is a key mediator of intestinal inflammation and tumorigenesis. 28280036 1 38 theme Signal 131:136 arg1 transducer 138:147 Signal transducer 131:147 Signal transducer 131:147 Signal transducer and activator of transcription 3 (STAT3) is a key mediator of intestinal inflammation and tumorigenesis. 28280036 3 39 theme O-linked 417:424 arg1 O-GlcNAc 449:456 O-GlcNAc 449:456 O-GlcNAc 449:456 Here, we demonstrate that modification of STAT3 with O-linked β-N-acetylglucosamine (O-GlcNAc) on threonine 717 (T717) negatively regulates its phosphorylation and targets gene expression in macrophages. 28280036 3 39 theme O-linked 417:424 arg1 β-N-acetylglucosamine 426:446 O-linked β-N-acetylglucosamine 417:446 O-linked β-N-acetylglucosamine (O-GlcNAc) on threonine 717 (T717) 417:481 Here, we demonstrate that modification of STAT3 with O-linked β-N-acetylglucosamine (O-GlcNAc) on threonine 717 (T717) negatively regulates its phosphorylation and targets gene expression in macrophages. 28280036 7 40 theme modification 1167:1178 arg1 form 1141:1144 a new form 1135:1144 a new form 1135:1144 Thus, this study identifies a new form of posttranslational modification of STAT3, modulating its phosphorylation, and suggests the importance of immunometabolism on colonic inflammation and tumorigenesis. 28280036 2 41 theme molecular 267:275 arg1 mechanism 277:285 the molecular mechanism 263:285 the molecular mechanism that modulates STAT3 phosphorylation and activation 263:337 However, the molecular mechanism that modulates STAT3 phosphorylation and activation is not fully understood. 28280036 1 42 theme inflammation 222:233 arg1 mediator 199:206 a key mediator 193:206 a key mediator of intestinal inflammation and tumorigenesis 193:251 Signal transducer and activator of transcription 3 (STAT3) is a key mediator of intestinal inflammation and tumorigenesis. 28280036 1 42 theme inflammation 222:233 arg1 activator 153:161 activator 153:161 activator 153:161 Signal transducer and activator of transcription 3 (STAT3) is a key mediator of intestinal inflammation and tumorigenesis. 28280036 1 42 theme inflammation 222:233 arg1 transducer 138:147 Signal transducer 131:147 Signal transducer 131:147 Signal transducer and activator of transcription 3 (STAT3) is a key mediator of intestinal inflammation and tumorigenesis. 28280036 5 43 theme factor 816:821 arg1 Nrf2 844:847 Nrf2 844:847 Nrf2 844:847 The inhibitory effect of CUL3 on OGT expression is dependent on nuclear factor E2-related factor-2 (Nrf2), which binds to the Ogt promoter region and increases gene transcription. 28280036 5 43 theme factor 816:821 arg1 factor-2 834:841 nuclear factor E2-related factor-2 808:841 nuclear factor E2-related factor-2 (Nrf2) 808:848 The inhibitory effect of CUL3 on OGT expression is dependent on nuclear factor E2-related factor-2 (Nrf2), which binds to the Ogt promoter region and increases gene transcription. 28280036 5 44 theme gene 904:907 arg1 transcription 909:921 gene transcription 904:921 gene transcription 904:921 The inhibitory effect of CUL3 on OGT expression is dependent on nuclear factor E2-related factor-2 (Nrf2), which binds to the Ogt promoter region and increases gene transcription. 28280036 5 45 theme inhibitory 748:757 arg1 effect 759:764 The inhibitory effect 744:764 The inhibitory effect of CUL3 on OGT expression 744:790 The inhibitory effect of CUL3 on OGT expression is dependent on nuclear factor E2-related factor-2 (Nrf2), which binds to the Ogt promoter region and increases gene transcription. 28280036 5 45 theme inhibitory 748:757 arg1 dependent 795:803 dependent 795:803 dependent 795:803 The inhibitory effect of CUL3 on OGT expression is dependent on nuclear factor E2-related factor-2 (Nrf2), which binds to the Ogt promoter region and increases gene transcription. 28280036 5 46 from effect 759:764 arg1 expression 781:790 OGT expression 777:790 OGT expression 777:790 The inhibitory effect of CUL3 on OGT expression is dependent on nuclear factor E2-related factor-2 (Nrf2), which binds to the Ogt promoter region and increases gene transcription. 28280036 4 47 theme family 616:621 arg1 ligase 636:641 a cullin family E3 ubiquitin ligase 607:641 a cullin family E3 ubiquitin ligase 607:641 We further found that cullin 3 (CUL3), a cullin family E3 ubiquitin ligase, down-regulates the expression of the O-GlcNAc transferase (OGT) and inhibits STAT3 O-GlcNAcylation. 28280036 4 47 theme family 616:621 arg1 CUL3 600:603 cullin 3 (CUL3) 590:604 cullin 3 (CUL3) 590:604 We further found that cullin 3 (CUL3), a cullin family E3 ubiquitin ligase, down-regulates the expression of the O-GlcNAc transferase (OGT) and inhibits STAT3 O-GlcNAcylation. 28280036 3 48 theme gene 536:539 arg1 expression 541:550 gene expression 536:550 gene expression in macrophages 536:565 Here, we demonstrate that modification of STAT3 with O-linked β-N-acetylglucosamine (O-GlcNAc) on threonine 717 (T717) negatively regulates its phosphorylation and targets gene expression in macrophages. 28280036 1 49 theme tumorigenesis 239:251 arg1 mediator 199:206 a key mediator 193:206 a key mediator of intestinal inflammation and tumorigenesis 193:251 Signal transducer and activator of transcription 3 (STAT3) is a key mediator of intestinal inflammation and tumorigenesis. 28280036 1 49 theme tumorigenesis 239:251 arg1 activator 153:161 activator 153:161 activator 153:161 Signal transducer and activator of transcription 3 (STAT3) is a key mediator of intestinal inflammation and tumorigenesis. 28280036 1 49 theme tumorigenesis 239:251 arg1 transducer 138:147 Signal transducer 131:147 Signal transducer 131:147 Signal transducer and activator of transcription 3 (STAT3) is a key mediator of intestinal inflammation and tumorigenesis. 28280036 0 50 theme OGT 70:72 arg1 expression 74:83 OGT expression 70:83 OGT expression 70:83 Myeloid-derived cullin 3 promotes STAT3 phosphorylation by inhibiting OGT expression and protects against intestinal inflammation. 28280036 4 51 theme ubiquitin 626:634 arg1 ligase 636:641 a cullin family E3 ubiquitin ligase 607:641 a cullin family E3 ubiquitin ligase 607:641 We further found that cullin 3 (CUL3), a cullin family E3 ubiquitin ligase, down-regulates the expression of the O-GlcNAc transferase (OGT) and inhibits STAT3 O-GlcNAcylation. 28280036 4 51 theme ubiquitin 626:634 arg1 CUL3 600:603 cullin 3 (CUL3) 590:604 cullin 3 (CUL3) 590:604 We further found that cullin 3 (CUL3), a cullin family E3 ubiquitin ligase, down-regulates the expression of the O-GlcNAc transferase (OGT) and inhibits STAT3 O-GlcNAcylation. 28280036 1 52 theme transcription 166:178 arg1 mediator 199:206 a key mediator 193:206 a key mediator of intestinal inflammation and tumorigenesis 193:251 Signal transducer and activator of transcription 3 (STAT3) is a key mediator of intestinal inflammation and tumorigenesis. 28280036 1 52 theme transcription 166:178 arg1 STAT3 183:187 STAT3 183:187 STAT3 183:187 Signal transducer and activator of transcription 3 (STAT3) is a key mediator of intestinal inflammation and tumorigenesis. 28280036 1 52 theme transcription 166:178 arg1 activator 153:161 activator 153:161 activator 153:161 Signal transducer and activator of transcription 3 (STAT3) is a key mediator of intestinal inflammation and tumorigenesis. 28280036 1 52 theme transcription 166:178 arg1 transducer 138:147 Signal transducer 131:147 Signal transducer 131:147 Signal transducer and activator of transcription 3 (STAT3) is a key mediator of intestinal inflammation and tumorigenesis. 28280036 4 53 theme cullin 609:614 arg1 ligase 636:641 a cullin family E3 ubiquitin ligase 607:641 a cullin family E3 ubiquitin ligase 607:641 We further found that cullin 3 (CUL3), a cullin family E3 ubiquitin ligase, down-regulates the expression of the O-GlcNAc transferase (OGT) and inhibits STAT3 O-GlcNAcylation. 28280036 4 53 theme cullin 609:614 arg1 CUL3 600:603 cullin 3 (CUL3) 590:604 cullin 3 (CUL3) 590:604 We further found that cullin 3 (CUL3), a cullin family E3 ubiquitin ligase, down-regulates the expression of the O-GlcNAc transferase (OGT) and inhibits STAT3 O-GlcNAcylation. 27004849 3 0 from biosynthesis 682:693 arg1 colon 739:743 the colon 735:743 the colon 735:743 In particular, we observed an enrichment of mutations in genes (B3GNT2, B4GALT2, ST6GALNAC2) involved in the biosynthesis of N- and Cores 1-3 O-linked glycans in the colon, accounting for ~16% of the CRCs tested. 27004849 5 1 theme migratory 1204:1212 arg1 potential 1214:1222 the migratory potential 1200:1222 the migratory potential of colon carcinoma cells 1200:1247 Systematic biochemical and phenotypic characterization of the candidate wild-type and mutant glycosyltransferases demonstrated these mutations as either markedly altering protein localization, post-translational modification, encoded enzymatic activities and/or the migratory potential of colon carcinoma cells. 27004849 5 2 theme encoded 1164:1170 arg1 activities 1182:1191 encoded enzymatic activities 1164:1191 encoded enzymatic activities 1164:1191 Systematic biochemical and phenotypic characterization of the candidate wild-type and mutant glycosyltransferases demonstrated these mutations as either markedly altering protein localization, post-translational modification, encoded enzymatic activities and/or the migratory potential of colon carcinoma cells. 27004849 2 3 theme new 499:501 arg1 genes 550:554 12 new significantly mutated glycosylation-associated genes 496:554 12 new significantly mutated glycosylation-associated genes in colon cancer 496:570 We performed targeted re-sequencing of 430 glycosylation-associated genes in a series of patient-derived CRC cell lines (N = 31) and matched primary tumor tissues, identifying 12 new significantly mutated glycosylation-associated genes in colon cancer. 27004849 3 4 theme N- 698:699 arg1 biosynthesis 682:693 the biosynthesis 678:693 the biosynthesis of N- and Cores 1-3 O-linked glycans in the colon 678:743 In particular, we observed an enrichment of mutations in genes (B3GNT2, B4GALT2, ST6GALNAC2) involved in the biosynthesis of N- and Cores 1-3 O-linked glycans in the colon, accounting for ~16% of the CRCs tested. 27004849 6 5 theme aberrant 1359:1366 arg1 glycosylation 1368:1380 aberrant glycosylation 1359:1380 aberrant glycosylation 1359:1380 These findings suggest that functionally deleterious mutations in glycosyltransferase genes in part underlie aberrant glycosylation, and contribute to the pathogenesis of molecular subsets of colon and other gastrointestinal malignancies. 27004849 1 6 theme widespread 192:201 arg1 glycosylation 151:163 aberrant protein glycosylation 134:163 aberrant protein glycosylation 134:163 The molecular basis of aberrant protein glycosylation, a pathological alteration widespread in colorectal cancers (CRC), and the mechanisms by which it contributes to tumor progression remain largely unknown. 27004849 1 6 theme widespread 192:201 arg1 alteration 181:190 a pathological alteration 166:190 a pathological alteration widespread in colorectal cancers (CRC) 166:229 The molecular basis of aberrant protein glycosylation, a pathological alteration widespread in colorectal cancers (CRC), and the mechanisms by which it contributes to tumor progression remain largely unknown. 27004849 6 7 theme molecular 1421:1429 arg1 subsets 1431:1437 molecular subsets 1421:1437 molecular subsets of colon and other gastrointestinal malignancies 1421:1486 These findings suggest that functionally deleterious mutations in glycosyltransferase genes in part underlie aberrant glycosylation, and contribute to the pathogenesis of molecular subsets of colon and other gastrointestinal malignancies. 27004849 5 8 theme biochemical 949:959 arg1 characterization 976:991 Systematic biochemical and phenotypic characterization 938:991 Systematic biochemical and phenotypic characterization of the candidate wild-type and mutant glycosyltransferases 938:1050 Systematic biochemical and phenotypic characterization of the candidate wild-type and mutant glycosyltransferases demonstrated these mutations as either markedly altering protein localization, post-translational modification, encoded enzymatic activities and/or the migratory potential of colon carcinoma cells. 27004849 4 9 from mutations 864:872 arg1 cancers 929:935 other gastrointestinal cancers 906:935 other gastrointestinal cancers 906:935 Analysis of independent large-scale tumor tissue datasets confirmed recurrent mutations within these genes in colon and other gastrointestinal cancers. 27004849 4 9 from mutations 864:872 arg1 colon 896:900 colon 896:900 colon 896:900 Analysis of independent large-scale tumor tissue datasets confirmed recurrent mutations within these genes in colon and other gastrointestinal cancers. 27004849 1 10 from widespread 192:201 arg1 cancers 217:223 colorectal cancers 206:223 colorectal cancers (CRC) 206:229 The molecular basis of aberrant protein glycosylation, a pathological alteration widespread in colorectal cancers (CRC), and the mechanisms by which it contributes to tumor progression remain largely unknown. 27004849 1 10 from widespread 192:201 arg1 CRC 226:228 CRC 226:228 CRC 226:228 The molecular basis of aberrant protein glycosylation, a pathological alteration widespread in colorectal cancers (CRC), and the mechanisms by which it contributes to tumor progression remain largely unknown. 27004849 6 11 from mutations 1303:1311 arg1 genes 1336:1340 glycosyltransferase genes 1316:1340 glycosyltransferase genes 1316:1340 These findings suggest that functionally deleterious mutations in glycosyltransferase genes in part underlie aberrant glycosylation, and contribute to the pathogenesis of molecular subsets of colon and other gastrointestinal malignancies. 27004849 6 11 from mutations 1303:1311 arg1 part 1345:1348 part 1345:1348 part 1345:1348 These findings suggest that functionally deleterious mutations in glycosyltransferase genes in part underlie aberrant glycosylation, and contribute to the pathogenesis of molecular subsets of colon and other gastrointestinal malignancies. 27004849 6 12 theme gastrointestinal 1458:1473 arg1 malignancies 1475:1486 other gastrointestinal malignancies 1452:1486 other gastrointestinal malignancies 1452:1486 These findings suggest that functionally deleterious mutations in glycosyltransferase genes in part underlie aberrant glycosylation, and contribute to the pathogenesis of molecular subsets of colon and other gastrointestinal malignancies. 27004849 2 13 theme colon 559:563 arg1 cancer 565:570 colon cancer 559:570 colon cancer 559:570 We performed targeted re-sequencing of 430 glycosylation-associated genes in a series of patient-derived CRC cell lines (N = 31) and matched primary tumor tissues, identifying 12 new significantly mutated glycosylation-associated genes in colon cancer. 27004849 0 14 from landscapes 83:92 arg1 cancer 103:108 colon cancer 97:108 colon cancer 97:108 Biochemical and functional characterization of glycosylation-associated mutational landscapes in colon cancer. 27004849 5 15 theme post-translational 1131:1148 arg1 modification 1150:1161 post-translational modification 1131:1161 post-translational modification 1131:1161 Systematic biochemical and phenotypic characterization of the candidate wild-type and mutant glycosyltransferases demonstrated these mutations as either markedly altering protein localization, post-translational modification, encoded enzymatic activities and/or the migratory potential of colon carcinoma cells. 27004849 3 16 link O-linked 715:722 arg1 glycans 724:730 1-3 O-linked glycans 711:730 1-3 O-linked glycans 711:730 In particular, we observed an enrichment of mutations in genes (B3GNT2, B4GALT2, ST6GALNAC2) involved in the biosynthesis of N- and Cores 1-3 O-linked glycans in the colon, accounting for ~16% of the CRCs tested. 27004849 1 17 theme tumor 278:282 arg1 progression 284:294 tumor progression 278:294 tumor progression 278:294 The molecular basis of aberrant protein glycosylation, a pathological alteration widespread in colorectal cancers (CRC), and the mechanisms by which it contributes to tumor progression remain largely unknown. 27004849 6 18 theme malignancies 1475:1486 arg1 subsets 1431:1437 molecular subsets 1421:1437 molecular subsets of colon and other gastrointestinal malignancies 1421:1486 These findings suggest that functionally deleterious mutations in glycosyltransferase genes in part underlie aberrant glycosylation, and contribute to the pathogenesis of molecular subsets of colon and other gastrointestinal malignancies. 27004849 2 19 theme glycosylation-associated 363:386 arg1 genes 388:392 430 glycosylation-associated genes 359:392 430 glycosylation-associated genes 359:392 We performed targeted re-sequencing of 430 glycosylation-associated genes in a series of patient-derived CRC cell lines (N = 31) and matched primary tumor tissues, identifying 12 new significantly mutated glycosylation-associated genes in colon cancer. 27004849 4 20 theme datasets 835:842 arg1 Analysis 786:793 Analysis 786:793 Analysis of independent large-scale tumor tissue datasets 786:842 Analysis of independent large-scale tumor tissue datasets confirmed recurrent mutations within these genes in colon and other gastrointestinal cancers. 27004849 5 21 theme candidate 1000:1008 arg1 glycosyltransferases 1031:1050 the candidate wild-type and mutant glycosyltransferases 996:1050 the candidate wild-type and mutant glycosyltransferases 996:1050 Systematic biochemical and phenotypic characterization of the candidate wild-type and mutant glycosyltransferases demonstrated these mutations as either markedly altering protein localization, post-translational modification, encoded enzymatic activities and/or the migratory potential of colon carcinoma cells. 27004849 2 22 theme cell 429:432 arg1 N = 31 441:446 N = 31 441:446 N = 31 441:446 We performed targeted re-sequencing of 430 glycosylation-associated genes in a series of patient-derived CRC cell lines (N = 31) and matched primary tumor tissues, identifying 12 new significantly mutated glycosylation-associated genes in colon cancer. 27004849 2 22 theme cell 429:432 arg1 lines 434:438 patient-derived CRC cell lines 409:438 patient-derived CRC cell lines (N = 31) 409:447 We performed targeted re-sequencing of 430 glycosylation-associated genes in a series of patient-derived CRC cell lines (N = 31) and matched primary tumor tissues, identifying 12 new significantly mutated glycosylation-associated genes in colon cancer. 27004849 2 23 theme tissues 475:481 arg1 series 399:404 a series 397:404 a series of patient-derived CRC cell lines (N = 31) and matched primary tumor tissues 397:481 We performed targeted re-sequencing of 430 glycosylation-associated genes in a series of patient-derived CRC cell lines (N = 31) and matched primary tumor tissues, identifying 12 new significantly mutated glycosylation-associated genes in colon cancer. 27004849 3 24 theme O-linked 715:722 arg1 glycans 724:730 1-3 O-linked glycans 711:730 1-3 O-linked glycans 711:730 In particular, we observed an enrichment of mutations in genes (B3GNT2, B4GALT2, ST6GALNAC2) involved in the biosynthesis of N- and Cores 1-3 O-linked glycans in the colon, accounting for ~16% of the CRCs tested. 27004849 4 25 theme tissue 828:833 arg1 datasets 835:842 independent large-scale tumor tissue datasets 798:842 independent large-scale tumor tissue datasets 798:842 Analysis of independent large-scale tumor tissue datasets confirmed recurrent mutations within these genes in colon and other gastrointestinal cancers. 27004849 2 26 theme primary 461:467 arg1 tissues 475:481 matched primary tumor tissues 453:481 matched primary tumor tissues 453:481 We performed targeted re-sequencing of 430 glycosylation-associated genes in a series of patient-derived CRC cell lines (N = 31) and matched primary tumor tissues, identifying 12 new significantly mutated glycosylation-associated genes in colon cancer. 27004849 2 27 theme CRC 425:427 arg1 N = 31 441:446 N = 31 441:446 N = 31 441:446 We performed targeted re-sequencing of 430 glycosylation-associated genes in a series of patient-derived CRC cell lines (N = 31) and matched primary tumor tissues, identifying 12 new significantly mutated glycosylation-associated genes in colon cancer. 27004849 2 27 theme CRC 425:427 arg1 lines 434:438 patient-derived CRC cell lines 409:438 patient-derived CRC cell lines (N = 31) 409:447 We performed targeted re-sequencing of 430 glycosylation-associated genes in a series of patient-derived CRC cell lines (N = 31) and matched primary tumor tissues, identifying 12 new significantly mutated glycosylation-associated genes in colon cancer. 27004849 2 28 theme tumor 469:473 arg1 tissues 475:481 matched primary tumor tissues 453:481 matched primary tumor tissues 453:481 We performed targeted re-sequencing of 430 glycosylation-associated genes in a series of patient-derived CRC cell lines (N = 31) and matched primary tumor tissues, identifying 12 new significantly mutated glycosylation-associated genes in colon cancer. 27004849 4 29 theme recurrent 854:862 arg1 mutations 864:872 recurrent mutations 854:872 recurrent mutations within these genes in colon and other gastrointestinal cancers 854:935 Analysis of independent large-scale tumor tissue datasets confirmed recurrent mutations within these genes in colon and other gastrointestinal cancers. 27004849 2 30 theme glycosylation-associated 525:548 arg1 genes 550:554 12 new significantly mutated glycosylation-associated genes 496:554 12 new significantly mutated glycosylation-associated genes in colon cancer 496:570 We performed targeted re-sequencing of 430 glycosylation-associated genes in a series of patient-derived CRC cell lines (N = 31) and matched primary tumor tissues, identifying 12 new significantly mutated glycosylation-associated genes in colon cancer. 27004849 2 31 theme targeted 333:340 arg1 re-sequencing 342:354 targeted re-sequencing 333:354 targeted re-sequencing of 430 glycosylation-associated genes 333:392 We performed targeted re-sequencing of 430 glycosylation-associated genes in a series of patient-derived CRC cell lines (N = 31) and matched primary tumor tissues, identifying 12 new significantly mutated glycosylation-associated genes in colon cancer. 27004849 5 32 theme enzymatic 1172:1180 arg1 activities 1182:1191 encoded enzymatic activities 1164:1191 encoded enzymatic activities 1164:1191 Systematic biochemical and phenotypic characterization of the candidate wild-type and mutant glycosyltransferases demonstrated these mutations as either markedly altering protein localization, post-translational modification, encoded enzymatic activities and/or the migratory potential of colon carcinoma cells. 27004849 2 33 theme patient-derived 409:423 arg1 N = 31 441:446 N = 31 441:446 N = 31 441:446 We performed targeted re-sequencing of 430 glycosylation-associated genes in a series of patient-derived CRC cell lines (N = 31) and matched primary tumor tissues, identifying 12 new significantly mutated glycosylation-associated genes in colon cancer. 27004849 2 33 theme patient-derived 409:423 arg1 lines 434:438 patient-derived CRC cell lines 409:438 patient-derived CRC cell lines (N = 31) 409:447 We performed targeted re-sequencing of 430 glycosylation-associated genes in a series of patient-derived CRC cell lines (N = 31) and matched primary tumor tissues, identifying 12 new significantly mutated glycosylation-associated genes in colon cancer. 27004849 0 34 theme Biochemical 0:10 arg1 characterization 27:42 Biochemical and functional characterization 0:42 Biochemical and functional characterization of glycosylation-associated mutational landscapes in colon cancer. 0:109 Biochemical and functional characterization of glycosylation-associated mutational landscapes in colon cancer. 27004849 3 35 dep N- 698:699 arg1 glycans 724:730 1-3 O-linked glycans 711:730 1-3 O-linked glycans 711:730 In particular, we observed an enrichment of mutations in genes (B3GNT2, B4GALT2, ST6GALNAC2) involved in the biosynthesis of N- and Cores 1-3 O-linked glycans in the colon, accounting for ~16% of the CRCs tested. 27004849 1 36 theme molecular 115:123 arg1 basis 125:129 The molecular basis 111:129 The molecular basis of aberrant protein glycosylation, a pathological alteration widespread in colorectal cancers (CRC), 111:230 The molecular basis of aberrant protein glycosylation, a pathological alteration widespread in colorectal cancers (CRC), and the mechanisms by which it contributes to tumor progression remain largely unknown. 27004849 3 37 dep genes 630:634 arg1 B3GNT2 637:642 B3GNT2 637:642 B3GNT2 637:642 In particular, we observed an enrichment of mutations in genes (B3GNT2, B4GALT2, ST6GALNAC2) involved in the biosynthesis of N- and Cores 1-3 O-linked glycans in the colon, accounting for ~16% of the CRCs tested. 27004849 3 37 dep genes 630:634 arg1 ST6GALNAC2 654:663 ST6GALNAC2 654:663 ST6GALNAC2 654:663 In particular, we observed an enrichment of mutations in genes (B3GNT2, B4GALT2, ST6GALNAC2) involved in the biosynthesis of N- and Cores 1-3 O-linked glycans in the colon, accounting for ~16% of the CRCs tested. 27004849 3 37 dep genes 630:634 arg1 B4GALT2 645:651 B4GALT2 645:651 B4GALT2 645:651 In particular, we observed an enrichment of mutations in genes (B3GNT2, B4GALT2, ST6GALNAC2) involved in the biosynthesis of N- and Cores 1-3 O-linked glycans in the colon, accounting for ~16% of the CRCs tested. 27004849 2 38 theme matched 453:459 arg1 tissues 475:481 matched primary tumor tissues 453:481 matched primary tumor tissues 453:481 We performed targeted re-sequencing of 430 glycosylation-associated genes in a series of patient-derived CRC cell lines (N = 31) and matched primary tumor tissues, identifying 12 new significantly mutated glycosylation-associated genes in colon cancer. 27004849 6 39 theme deleterious 1291:1301 arg1 mutations 1303:1311 functionally deleterious mutations 1278:1311 functionally deleterious mutations in glycosyltransferase genes in part 1278:1348 These findings suggest that functionally deleterious mutations in glycosyltransferase genes in part underlie aberrant glycosylation, and contribute to the pathogenesis of molecular subsets of colon and other gastrointestinal malignancies. 27004849 6 40 theme other 1452:1456 arg1 malignancies 1475:1486 other gastrointestinal malignancies 1452:1486 other gastrointestinal malignancies 1452:1486 These findings suggest that functionally deleterious mutations in glycosyltransferase genes in part underlie aberrant glycosylation, and contribute to the pathogenesis of molecular subsets of colon and other gastrointestinal malignancies. 27004849 4 41 theme large-scale 810:820 arg1 datasets 835:842 independent large-scale tumor tissue datasets 798:842 independent large-scale tumor tissue datasets 798:842 Analysis of independent large-scale tumor tissue datasets confirmed recurrent mutations within these genes in colon and other gastrointestinal cancers. 27004849 5 42 theme phenotypic 965:974 arg1 characterization 976:991 Systematic biochemical and phenotypic characterization 938:991 Systematic biochemical and phenotypic characterization of the candidate wild-type and mutant glycosyltransferases 938:1050 Systematic biochemical and phenotypic characterization of the candidate wild-type and mutant glycosyltransferases demonstrated these mutations as either markedly altering protein localization, post-translational modification, encoded enzymatic activities and/or the migratory potential of colon carcinoma cells. 27004849 0 43 theme functional 16:25 arg1 characterization 27:42 Biochemical and functional characterization 0:42 Biochemical and functional characterization of glycosylation-associated mutational landscapes in colon cancer. 0:109 Biochemical and functional characterization of glycosylation-associated mutational landscapes in colon cancer. 27004849 4 44 theme gastrointestinal 912:927 arg1 cancers 929:935 other gastrointestinal cancers 906:935 other gastrointestinal cancers 906:935 Analysis of independent large-scale tumor tissue datasets confirmed recurrent mutations within these genes in colon and other gastrointestinal cancers. 27004849 2 45 link patient-derived 409:423 arg1 N = 31 441:446 N = 31 441:446 N = 31 441:446 We performed targeted re-sequencing of 430 glycosylation-associated genes in a series of patient-derived CRC cell lines (N = 31) and matched primary tumor tissues, identifying 12 new significantly mutated glycosylation-associated genes in colon cancer. 27004849 2 45 link patient-derived 409:423 arg1 lines 434:438 patient-derived CRC cell lines 409:438 patient-derived CRC cell lines (N = 31) 409:447 We performed targeted re-sequencing of 430 glycosylation-associated genes in a series of patient-derived CRC cell lines (N = 31) and matched primary tumor tissues, identifying 12 new significantly mutated glycosylation-associated genes in colon cancer. 27004849 2 46 theme genes 388:392 arg1 re-sequencing 342:354 targeted re-sequencing 333:354 targeted re-sequencing of 430 glycosylation-associated genes 333:392 We performed targeted re-sequencing of 430 glycosylation-associated genes in a series of patient-derived CRC cell lines (N = 31) and matched primary tumor tissues, identifying 12 new significantly mutated glycosylation-associated genes in colon cancer. 27004849 0 47 theme glycosylation-associated 47:70 arg1 landscapes 83:92 glycosylation-associated mutational landscapes 47:92 glycosylation-associated mutational landscapes in colon cancer 47:108 Biochemical and functional characterization of glycosylation-associated mutational landscapes in colon cancer. 27004849 6 48 theme colon 1442:1446 arg1 subsets 1431:1437 molecular subsets 1421:1437 molecular subsets of colon and other gastrointestinal malignancies 1421:1486 These findings suggest that functionally deleterious mutations in glycosyltransferase genes in part underlie aberrant glycosylation, and contribute to the pathogenesis of molecular subsets of colon and other gastrointestinal malignancies. 27004849 0 49 from cancer 103:108 arg1 characterization 27:42 Biochemical and functional characterization 0:42 Biochemical and functional characterization of glycosylation-associated mutational landscapes in colon cancer. 0:109 Biochemical and functional characterization of glycosylation-associated mutational landscapes in colon cancer. 27004849 4 50 theme independent 798:808 arg1 datasets 835:842 independent large-scale tumor tissue datasets 798:842 independent large-scale tumor tissue datasets 798:842 Analysis of independent large-scale tumor tissue datasets confirmed recurrent mutations within these genes in colon and other gastrointestinal cancers. 27004849 3 51 from enrichment 603:612 arg1 genes 630:634 genes 630:634 genes (B3GNT2, B4GALT2, ST6GALNAC2) involved in the biosynthesis of N- and Cores 1-3 O-linked glycans in the colon 630:743 In particular, we observed an enrichment of mutations in genes (B3GNT2, B4GALT2, ST6GALNAC2) involved in the biosynthesis of N- and Cores 1-3 O-linked glycans in the colon, accounting for ~16% of the CRCs tested. 27004849 5 52 theme colon 1227:1231 arg1 cells 1243:1247 colon carcinoma cells 1227:1247 colon carcinoma cells 1227:1247 Systematic biochemical and phenotypic characterization of the candidate wild-type and mutant glycosyltransferases demonstrated these mutations as either markedly altering protein localization, post-translational modification, encoded enzymatic activities and/or the migratory potential of colon carcinoma cells. 27004849 2 53 theme lines 434:438 arg1 series 399:404 a series 397:404 a series of patient-derived CRC cell lines (N = 31) and matched primary tumor tissues 397:481 We performed targeted re-sequencing of 430 glycosylation-associated genes in a series of patient-derived CRC cell lines (N = 31) and matched primary tumor tissues, identifying 12 new significantly mutated glycosylation-associated genes in colon cancer. 27004849 0 54 theme landscapes 83:92 arg1 characterization 27:42 Biochemical and functional characterization 0:42 Biochemical and functional characterization of glycosylation-associated mutational landscapes in colon cancer. 0:109 Biochemical and functional characterization of glycosylation-associated mutational landscapes in colon cancer. 27004849 5 55 theme carcinoma 1233:1241 arg1 cells 1243:1247 colon carcinoma cells 1227:1247 colon carcinoma cells 1227:1247 Systematic biochemical and phenotypic characterization of the candidate wild-type and mutant glycosyltransferases demonstrated these mutations as either markedly altering protein localization, post-translational modification, encoded enzymatic activities and/or the migratory potential of colon carcinoma cells. 27004849 6 56 theme subsets 1431:1437 arg1 pathogenesis 1405:1416 the pathogenesis 1401:1416 the pathogenesis of molecular subsets of colon and other gastrointestinal malignancies 1401:1486 These findings suggest that functionally deleterious mutations in glycosyltransferase genes in part underlie aberrant glycosylation, and contribute to the pathogenesis of molecular subsets of colon and other gastrointestinal malignancies. 27004849 4 57 theme tumor 822:826 arg1 datasets 835:842 independent large-scale tumor tissue datasets 798:842 independent large-scale tumor tissue datasets 798:842 Analysis of independent large-scale tumor tissue datasets confirmed recurrent mutations within these genes in colon and other gastrointestinal cancers. 27004849 1 58 theme aberrant 134:141 arg1 glycosylation 151:163 aberrant protein glycosylation 134:163 aberrant protein glycosylation 134:163 The molecular basis of aberrant protein glycosylation, a pathological alteration widespread in colorectal cancers (CRC), and the mechanisms by which it contributes to tumor progression remain largely unknown. 27004849 1 58 theme aberrant 134:141 arg1 alteration 181:190 a pathological alteration 166:190 a pathological alteration widespread in colorectal cancers (CRC) 166:229 The molecular basis of aberrant protein glycosylation, a pathological alteration widespread in colorectal cancers (CRC), and the mechanisms by which it contributes to tumor progression remain largely unknown. 27004849 0 59 theme mutational 72:81 arg1 landscapes 83:92 glycosylation-associated mutational landscapes 47:92 glycosylation-associated mutational landscapes in colon cancer 47:108 Biochemical and functional characterization of glycosylation-associated mutational landscapes in colon cancer. 27004849 5 60 theme cells 1243:1247 arg1 potential 1214:1222 the migratory potential 1200:1222 the migratory potential of colon carcinoma cells 1200:1247 Systematic biochemical and phenotypic characterization of the candidate wild-type and mutant glycosyltransferases demonstrated these mutations as either markedly altering protein localization, post-translational modification, encoded enzymatic activities and/or the migratory potential of colon carcinoma cells. 27004849 3 61 theme Cores 705:709 arg1 biosynthesis 682:693 the biosynthesis 678:693 the biosynthesis of N- and Cores 1-3 O-linked glycans in the colon 678:743 In particular, we observed an enrichment of mutations in genes (B3GNT2, B4GALT2, ST6GALNAC2) involved in the biosynthesis of N- and Cores 1-3 O-linked glycans in the colon, accounting for ~16% of the CRCs tested. 27004849 3 62 theme mutations 617:625 arg1 enrichment 603:612 an enrichment 600:612 an enrichment of mutations in genes (B3GNT2, B4GALT2, ST6GALNAC2) involved in the biosynthesis of N- and Cores 1-3 O-linked glycans in the colon 600:743 In particular, we observed an enrichment of mutations in genes (B3GNT2, B4GALT2, ST6GALNAC2) involved in the biosynthesis of N- and Cores 1-3 O-linked glycans in the colon, accounting for ~16% of the CRCs tested. 27004849 1 63 theme protein 143:149 arg1 glycosylation 151:163 aberrant protein glycosylation 134:163 aberrant protein glycosylation 134:163 The molecular basis of aberrant protein glycosylation, a pathological alteration widespread in colorectal cancers (CRC), and the mechanisms by which it contributes to tumor progression remain largely unknown. 27004849 1 63 theme protein 143:149 arg1 alteration 181:190 a pathological alteration 166:190 a pathological alteration widespread in colorectal cancers (CRC) 166:229 The molecular basis of aberrant protein glycosylation, a pathological alteration widespread in colorectal cancers (CRC), and the mechanisms by which it contributes to tumor progression remain largely unknown. 27004849 6 64 theme glycosyltransferase 1316:1334 arg1 genes 1336:1340 glycosyltransferase genes 1316:1340 glycosyltransferase genes 1316:1340 These findings suggest that functionally deleterious mutations in glycosyltransferase genes in part underlie aberrant glycosylation, and contribute to the pathogenesis of molecular subsets of colon and other gastrointestinal malignancies. 27004849 4 65 theme other 906:910 arg1 cancers 929:935 other gastrointestinal cancers 906:935 other gastrointestinal cancers 906:935 Analysis of independent large-scale tumor tissue datasets confirmed recurrent mutations within these genes in colon and other gastrointestinal cancers. 27004849 2 66 from genes 550:554 arg1 cancer 565:570 colon cancer 559:570 colon cancer 559:570 We performed targeted re-sequencing of 430 glycosylation-associated genes in a series of patient-derived CRC cell lines (N = 31) and matched primary tumor tissues, identifying 12 new significantly mutated glycosylation-associated genes in colon cancer. 27004849 1 67 theme glycosylation 151:163 arg1 basis 125:129 The molecular basis 111:129 The molecular basis of aberrant protein glycosylation, a pathological alteration widespread in colorectal cancers (CRC), 111:230 The molecular basis of aberrant protein glycosylation, a pathological alteration widespread in colorectal cancers (CRC), and the mechanisms by which it contributes to tumor progression remain largely unknown. 27004849 1 67 theme glycosylation 151:163 arg1 mechanisms 240:249 the mechanisms 236:249 the mechanisms by which it contributes to tumor progression 236:294 The molecular basis of aberrant protein glycosylation, a pathological alteration widespread in colorectal cancers (CRC), and the mechanisms by which it contributes to tumor progression remain largely unknown. 27004849 5 68 theme wild-type 1010:1018 arg1 glycosyltransferases 1031:1050 the candidate wild-type and mutant glycosyltransferases 996:1050 the candidate wild-type and mutant glycosyltransferases 996:1050 Systematic biochemical and phenotypic characterization of the candidate wild-type and mutant glycosyltransferases demonstrated these mutations as either markedly altering protein localization, post-translational modification, encoded enzymatic activities and/or the migratory potential of colon carcinoma cells. 27004849 5 69 theme protein 1109:1115 arg1 localization 1117:1128 protein localization 1109:1128 protein localization 1109:1128 Systematic biochemical and phenotypic characterization of the candidate wild-type and mutant glycosyltransferases demonstrated these mutations as either markedly altering protein localization, post-translational modification, encoded enzymatic activities and/or the migratory potential of colon carcinoma cells. 27004849 5 70 theme mutant 1024:1029 arg1 glycosyltransferases 1031:1050 the candidate wild-type and mutant glycosyltransferases 996:1050 the candidate wild-type and mutant glycosyltransferases 996:1050 Systematic biochemical and phenotypic characterization of the candidate wild-type and mutant glycosyltransferases demonstrated these mutations as either markedly altering protein localization, post-translational modification, encoded enzymatic activities and/or the migratory potential of colon carcinoma cells. 27004849 1 71 from cancers 217:223 arg1 widespread 192:201 widespread 192:201 widespread 192:201 The molecular basis of aberrant protein glycosylation, a pathological alteration widespread in colorectal cancers (CRC), and the mechanisms by which it contributes to tumor progression remain largely unknown. 27004849 5 72 theme Systematic 938:947 arg1 characterization 976:991 Systematic biochemical and phenotypic characterization 938:991 Systematic biochemical and phenotypic characterization of the candidate wild-type and mutant glycosyltransferases 938:1050 Systematic biochemical and phenotypic characterization of the candidate wild-type and mutant glycosyltransferases demonstrated these mutations as either markedly altering protein localization, post-translational modification, encoded enzymatic activities and/or the migratory potential of colon carcinoma cells. 27004849 0 73 theme colon 97:101 arg1 cancer 103:108 colon cancer 97:108 colon cancer 97:108 Biochemical and functional characterization of glycosylation-associated mutational landscapes in colon cancer. 27004849 5 74 theme glycosyltransferases 1031:1050 arg1 characterization 976:991 Systematic biochemical and phenotypic characterization 938:991 Systematic biochemical and phenotypic characterization of the candidate wild-type and mutant glycosyltransferases 938:1050 Systematic biochemical and phenotypic characterization of the candidate wild-type and mutant glycosyltransferases demonstrated these mutations as either markedly altering protein localization, post-translational modification, encoded enzymatic activities and/or the migratory potential of colon carcinoma cells. 27004849 1 75 theme colorectal 206:215 arg1 cancers 217:223 colorectal cancers 206:223 colorectal cancers (CRC) 206:229 The molecular basis of aberrant protein glycosylation, a pathological alteration widespread in colorectal cancers (CRC), and the mechanisms by which it contributes to tumor progression remain largely unknown. 27004849 1 75 theme colorectal 206:215 arg1 CRC 226:228 CRC 226:228 CRC 226:228 The molecular basis of aberrant protein glycosylation, a pathological alteration widespread in colorectal cancers (CRC), and the mechanisms by which it contributes to tumor progression remain largely unknown. 27004849 3 76 theme CRCs 773:776 arg1 % 764:764 ~16% 761:764 ~16% of the CRCs tested 761:783 In particular, we observed an enrichment of mutations in genes (B3GNT2, B4GALT2, ST6GALNAC2) involved in the biosynthesis of N- and Cores 1-3 O-linked glycans in the colon, accounting for ~16% of the CRCs tested. 27004849 3 76 theme CRCs 773:776 arg1 CRCs 773:776 the CRCs 769:776 the CRCs tested 769:783 In particular, we observed an enrichment of mutations in genes (B3GNT2, B4GALT2, ST6GALNAC2) involved in the biosynthesis of N- and Cores 1-3 O-linked glycans in the colon, accounting for ~16% of the CRCs tested. 27004849 2 77 theme mutated 517:523 arg1 genes 550:554 12 new significantly mutated glycosylation-associated genes 496:554 12 new significantly mutated glycosylation-associated genes in colon cancer 496:570 We performed targeted re-sequencing of 430 glycosylation-associated genes in a series of patient-derived CRC cell lines (N = 31) and matched primary tumor tissues, identifying 12 new significantly mutated glycosylation-associated genes in colon cancer. 27004849 0 78 from characterization 27:42 arg1 cancer 103:108 colon cancer 97:108 colon cancer 97:108 Biochemical and functional characterization of glycosylation-associated mutational landscapes in colon cancer. 27004849 1 79 theme pathological 168:179 arg1 glycosylation 151:163 aberrant protein glycosylation 134:163 aberrant protein glycosylation 134:163 The molecular basis of aberrant protein glycosylation, a pathological alteration widespread in colorectal cancers (CRC), and the mechanisms by which it contributes to tumor progression remain largely unknown. 27004849 1 79 theme pathological 168:179 arg1 alteration 181:190 a pathological alteration 166:190 a pathological alteration widespread in colorectal cancers (CRC) 166:229 The molecular basis of aberrant protein glycosylation, a pathological alteration widespread in colorectal cancers (CRC), and the mechanisms by which it contributes to tumor progression remain largely unknown. 26854602 0 0 theme linkage 88:94 arg1 triplet 96:102 Cys-NO linkage triplet 81:102 Cys-NO linkage triplet 81:102 Aβ-affected pathogenic induction of S-nitrosylation of OGT and identification of Cys-NO linkage triplet. 26854602 6 1 theme synergistic 991:1001 arg1 connection 1003:1012 synergistic connection 991:1012 synergistic connection between SNO-OGT and GSK3β activation 991:1049 In parallel with SNO-OGT-mediated tau hypo-O-GlcNAcylation, Aβ led to SNO-Akt-mediated GSK3β activation for tau phosphorylation, suggesting that tau hyperphosphorylation is established by synergistic connection between SNO-OGT and GSK3β activation. 26854602 10 2 theme triple 1850:1855 arg1 Cys845 1857:1862 triple Cys845 1850:1862 triple Cys845 1850:1862 Furthermore, our Cys mapping demonstrates that cysteine-nitric oxide (Cys-NO) linkages in SNO-OGT occur at triple Cys845, Cys921, and Cys965 residues in C-terminal catalytic domain (C-CAT), suggesting that Cys-NO linkage triplet in SNO-OGT is associated with null OGT activity. 26854602 10 3 from residues 1884:1891 arg1 C-CAT 1925:1929 C-CAT 1925:1929 C-CAT 1925:1929 Furthermore, our Cys mapping demonstrates that cysteine-nitric oxide (Cys-NO) linkages in SNO-OGT occur at triple Cys845, Cys921, and Cys965 residues in C-terminal catalytic domain (C-CAT), suggesting that Cys-NO linkage triplet in SNO-OGT is associated with null OGT activity. 26854602 10 3 from residues 1884:1891 arg1 domain 1917:1922 C-terminal catalytic domain 1896:1922 C-terminal catalytic domain (C-CAT) 1896:1930 Furthermore, our Cys mapping demonstrates that cysteine-nitric oxide (Cys-NO) linkages in SNO-OGT occur at triple Cys845, Cys921, and Cys965 residues in C-terminal catalytic domain (C-CAT), suggesting that Cys-NO linkage triplet in SNO-OGT is associated with null OGT activity. 26854602 4 4 theme Aβ-triggered 625:636 arg1 entry 643:647 Aβ-triggered Ca2+ entry 625:647 Aβ-triggered Ca2+ entry into cells and nNOS-catalyzed NO production 625:691 Our results support that underlying mechanism for induction of SNO-OGT comprises the concerted action of Aβ-triggered Ca2+ entry into cells and nNOS-catalyzed NO production. 26854602 0 5 theme Cys-NO 81:86 arg1 triplet 96:102 Cys-NO linkage triplet 81:102 Cys-NO linkage triplet 81:102 Aβ-affected pathogenic induction of S-nitrosylation of OGT and identification of Cys-NO linkage triplet. 26854602 9 6 theme pathogenic 1556:1565 arg1 induction 1515:1523 induction 1515:1523 induction of SNO-OGT by Aβ exposure 1515:1549 Together, these findings suggest that induction of SNO-OGT by Aβ exposure is a pathogenic mechanism to cause cellular hypo-O-GlcNAcylation by which Aβ neurotoxicity is executed, and conversely, hyper-O-GlcNAcylation within cells can defend against Aβ neurotoxicity. 26854602 9 6 theme pathogenic 1556:1565 arg1 mechanism 1567:1575 a pathogenic mechanism 1554:1575 a pathogenic mechanism to cause cellular hypo-O-GlcNAcylation by which Aβ neurotoxicity is executed 1554:1652 Together, these findings suggest that induction of SNO-OGT by Aβ exposure is a pathogenic mechanism to cause cellular hypo-O-GlcNAcylation by which Aβ neurotoxicity is executed, and conversely, hyper-O-GlcNAcylation within cells can defend against Aβ neurotoxicity. 26854602 10 7 theme linkage 1956:1962 arg1 triplet 1964:1970 Cys-NO linkage triplet 1949:1970 Cys-NO linkage triplet in SNO-OGT 1949:1981 Furthermore, our Cys mapping demonstrates that cysteine-nitric oxide (Cys-NO) linkages in SNO-OGT occur at triple Cys845, Cys921, and Cys965 residues in C-terminal catalytic domain (C-CAT), suggesting that Cys-NO linkage triplet in SNO-OGT is associated with null OGT activity. 26854602 9 8 theme SNO-OGT 1528:1534 arg1 induction 1515:1523 induction 1515:1523 induction of SNO-OGT by Aβ exposure 1515:1549 Together, these findings suggest that induction of SNO-OGT by Aβ exposure is a pathogenic mechanism to cause cellular hypo-O-GlcNAcylation by which Aβ neurotoxicity is executed, and conversely, hyper-O-GlcNAcylation within cells can defend against Aβ neurotoxicity. 26854602 9 8 theme SNO-OGT 1528:1534 arg1 mechanism 1567:1575 a pathogenic mechanism 1554:1575 a pathogenic mechanism to cause cellular hypo-O-GlcNAcylation by which Aβ neurotoxicity is executed 1554:1652 Together, these findings suggest that induction of SNO-OGT by Aβ exposure is a pathogenic mechanism to cause cellular hypo-O-GlcNAcylation by which Aβ neurotoxicity is executed, and conversely, hyper-O-GlcNAcylation within cells can defend against Aβ neurotoxicity. 26854602 4 9 theme underlying 545:554 arg1 mechanism 556:564 underlying mechanism 545:564 underlying mechanism for induction of SNO-OGT 545:589 Our results support that underlying mechanism for induction of SNO-OGT comprises the concerted action of Aβ-triggered Ca2+ entry into cells and nNOS-catalyzed NO production. 26854602 10 10 theme OGT 2007:2009 arg1 activity 2011:2018 null OGT activity 2002:2018 null OGT activity 2002:2018 Furthermore, our Cys mapping demonstrates that cysteine-nitric oxide (Cys-NO) linkages in SNO-OGT occur at triple Cys845, Cys921, and Cys965 residues in C-terminal catalytic domain (C-CAT), suggesting that Cys-NO linkage triplet in SNO-OGT is associated with null OGT activity. 26854602 8 11 theme SNO-OGT 1456:1462 arg1 entry 1417:1421 Aβ-triggered Ca2+ entry 1399:1421 not only Aβ-triggered Ca2+ entry into cells but also induction of SNO-OGT and SNO-Akt 1390:1474 Early time-course Aβ-monitoring assay revealed that premaintained hyper-O-GlcNAcylation inside cells blocked not only Aβ-triggered Ca2+ entry into cells but also induction of SNO-OGT and SNO-Akt. 26854602 8 11 theme SNO-OGT 1456:1462 arg1 induction 1443:1451 induction 1443:1451 not only Aβ-triggered Ca2+ entry into cells but also induction of SNO-OGT and SNO-Akt 1390:1474 Early time-course Aβ-monitoring assay revealed that premaintained hyper-O-GlcNAcylation inside cells blocked not only Aβ-triggered Ca2+ entry into cells but also induction of SNO-OGT and SNO-Akt. 26854602 10 12 theme cysteine-nitric 1790:1804 arg1 Cys-NO 1813:1818 Cys-NO 1813:1818 Cys-NO 1813:1818 Furthermore, our Cys mapping demonstrates that cysteine-nitric oxide (Cys-NO) linkages in SNO-OGT occur at triple Cys845, Cys921, and Cys965 residues in C-terminal catalytic domain (C-CAT), suggesting that Cys-NO linkage triplet in SNO-OGT is associated with null OGT activity. 26854602 10 12 theme cysteine-nitric 1790:1804 arg1 oxide 1806:1810 cysteine-nitric oxide 1790:1810 cysteine-nitric oxide (Cys-NO) linkages in SNO-OGT 1790:1839 Furthermore, our Cys mapping demonstrates that cysteine-nitric oxide (Cys-NO) linkages in SNO-OGT occur at triple Cys845, Cys921, and Cys965 residues in C-terminal catalytic domain (C-CAT), suggesting that Cys-NO linkage triplet in SNO-OGT is associated with null OGT activity. 26854602 2 13 link O-linked 258:265 arg1 SNO-OGT 300:306 SNO-OGT 300:306 SNO-OGT 300:306 Here, we found that S-nitrosylation of O-linked N-acetylglucosaminyltransferase (SNO-OGT) was induced by β-amyloid peptide (Aβ) exposure to SK-N-MC and SK-N-SH human neuroblastoma cells. 26854602 2 13 link O-linked 258:265 arg1 N-acetylglucosaminyltransferase 267:297 O-linked N-acetylglucosaminyltransferase 258:297 O-linked N-acetylglucosaminyltransferase (SNO-OGT) 258:307 Here, we found that S-nitrosylation of O-linked N-acetylglucosaminyltransferase (SNO-OGT) was induced by β-amyloid peptide (Aβ) exposure to SK-N-MC and SK-N-SH human neuroblastoma cells. 26854602 0 14 theme triplet 96:102 arg1 induction 23:31 Aβ-affected pathogenic induction 0:31 Aβ-affected pathogenic induction of S-nitrosylation of OGT 0:57 Aβ-affected pathogenic induction of S-nitrosylation of OGT and identification of Cys-NO linkage triplet. 26854602 0 14 theme triplet 96:102 arg1 identification 63:76 identification 63:76 identification of Cys-NO linkage triplet 63:102 Aβ-affected pathogenic induction of S-nitrosylation of OGT and identification of Cys-NO linkage triplet. 26854602 9 15 theme Aβ 1625:1626 arg1 neurotoxicity 1628:1640 Aβ neurotoxicity 1625:1640 Aβ neurotoxicity 1625:1640 Together, these findings suggest that induction of SNO-OGT by Aβ exposure is a pathogenic mechanism to cause cellular hypo-O-GlcNAcylation by which Aβ neurotoxicity is executed, and conversely, hyper-O-GlcNAcylation within cells can defend against Aβ neurotoxicity. 26854602 8 16 theme Aβ-triggered 1399:1410 arg1 entry 1417:1421 Aβ-triggered Ca2+ entry 1399:1421 not only Aβ-triggered Ca2+ entry into cells but also induction of SNO-OGT and SNO-Akt 1390:1474 Early time-course Aβ-monitoring assay revealed that premaintained hyper-O-GlcNAcylation inside cells blocked not only Aβ-triggered Ca2+ entry into cells but also induction of SNO-OGT and SNO-Akt. 26854602 4 17 theme Ca2+ 638:641 arg1 entry 643:647 Aβ-triggered Ca2+ entry 625:647 Aβ-triggered Ca2+ entry into cells and nNOS-catalyzed NO production 625:691 Our results support that underlying mechanism for induction of SNO-OGT comprises the concerted action of Aβ-triggered Ca2+ entry into cells and nNOS-catalyzed NO production. 26854602 7 18 theme OGT 1261:1263 arg1 overexpression 1265:1278 OGT overexpression 1261:1278 OGT overexpression 1261:1278 We also observed that Aβ-neurotoxicity including both reactive oxygen species (ROS) production and cell death was amplified with DON treatment, whereas it was restored by PUGNAc treatment, GlcNH2 treatment or OGT overexpression. 26854602 8 19 theme Ca2+ 1412:1415 arg1 entry 1417:1421 Aβ-triggered Ca2+ entry 1399:1421 not only Aβ-triggered Ca2+ entry into cells but also induction of SNO-OGT and SNO-Akt 1390:1474 Early time-course Aβ-monitoring assay revealed that premaintained hyper-O-GlcNAcylation inside cells blocked not only Aβ-triggered Ca2+ entry into cells but also induction of SNO-OGT and SNO-Akt. 26854602 6 20 with parallel 806:813 arg1 hypo-O-GlcNAcylation 841:860 SNO-OGT-mediated tau hypo-O-GlcNAcylation 820:860 SNO-OGT-mediated tau hypo-O-GlcNAcylation 820:860 In parallel with SNO-OGT-mediated tau hypo-O-GlcNAcylation, Aβ led to SNO-Akt-mediated GSK3β activation for tau phosphorylation, suggesting that tau hyperphosphorylation is established by synergistic connection between SNO-OGT and GSK3β activation. 26854602 4 21 theme NO 679:680 arg1 production 682:691 nNOS-catalyzed NO production 664:691 nNOS-catalyzed NO production 664:691 Our results support that underlying mechanism for induction of SNO-OGT comprises the concerted action of Aβ-triggered Ca2+ entry into cells and nNOS-catalyzed NO production. 26854602 8 22 theme SNO-Akt 1468:1474 arg1 entry 1417:1421 Aβ-triggered Ca2+ entry 1399:1421 not only Aβ-triggered Ca2+ entry into cells but also induction of SNO-OGT and SNO-Akt 1390:1474 Early time-course Aβ-monitoring assay revealed that premaintained hyper-O-GlcNAcylation inside cells blocked not only Aβ-triggered Ca2+ entry into cells but also induction of SNO-OGT and SNO-Akt. 26854602 8 22 theme SNO-Akt 1468:1474 arg1 induction 1443:1451 induction 1443:1451 not only Aβ-triggered Ca2+ entry into cells but also induction of SNO-OGT and SNO-Akt 1390:1474 Early time-course Aβ-monitoring assay revealed that premaintained hyper-O-GlcNAcylation inside cells blocked not only Aβ-triggered Ca2+ entry into cells but also induction of SNO-OGT and SNO-Akt. 26854602 2 23 theme neuroblastoma 385:397 arg1 cells 399:403 SK-N-MC and SK-N-SH human neuroblastoma cells 359:403 cells 399:403 Here, we found that S-nitrosylation of O-linked N-acetylglucosaminyltransferase (SNO-OGT) was induced by β-amyloid peptide (Aβ) exposure to SK-N-MC and SK-N-SH human neuroblastoma cells. 26854602 8 24 theme premaintained 1333:1345 arg1 cells 1376:1380 premaintained hyper-O-GlcNAcylation inside cells 1333:1380 premaintained hyper-O-GlcNAcylation inside cells 1333:1380 Early time-course Aβ-monitoring assay revealed that premaintained hyper-O-GlcNAcylation inside cells blocked not only Aβ-triggered Ca2+ entry into cells but also induction of SNO-OGT and SNO-Akt. 26854602 5 25 theme Aβ 789:790 arg1 treatment 792:800 Aβ treatment 789:800 Aβ treatment 789:800 Intriguingly, OGT was found to be associated with nNOS and its association was enhanced during Aβ treatment. 26854602 6 26 theme tau 948:950 arg1 hyperphosphorylation 952:971 tau hyperphosphorylation 948:971 tau hyperphosphorylation 948:971 In parallel with SNO-OGT-mediated tau hypo-O-GlcNAcylation, Aβ led to SNO-Akt-mediated GSK3β activation for tau phosphorylation, suggesting that tau hyperphosphorylation is established by synergistic connection between SNO-OGT and GSK3β activation. 26854602 8 27 theme Aβ-monitoring 1299:1311 arg1 assay 1313:1317 Early time-course Aβ-monitoring assay 1281:1317 Early time-course Aβ-monitoring assay 1281:1317 Early time-course Aβ-monitoring assay revealed that premaintained hyper-O-GlcNAcylation inside cells blocked not only Aβ-triggered Ca2+ entry into cells but also induction of SNO-OGT and SNO-Akt. 26854602 10 28 from linkages 1821:1828 arg1 SNO-OGT 1833:1839 SNO-OGT 1833:1839 SNO-OGT 1833:1839 Furthermore, our Cys mapping demonstrates that cysteine-nitric oxide (Cys-NO) linkages in SNO-OGT occur at triple Cys845, Cys921, and Cys965 residues in C-terminal catalytic domain (C-CAT), suggesting that Cys-NO linkage triplet in SNO-OGT is associated with null OGT activity. 26854602 2 29 theme N-acetylglucosaminyltransferase 267:297 arg1 S-nitrosylation 239:253 S-nitrosylation 239:253 S-nitrosylation of O-linked N-acetylglucosaminyltransferase (SNO-OGT) 239:307 Here, we found that S-nitrosylation of O-linked N-acetylglucosaminyltransferase (SNO-OGT) was induced by β-amyloid peptide (Aβ) exposure to SK-N-MC and SK-N-SH human neuroblastoma cells. 26854602 1 30 theme disease 189:195 arg1 pathogenesis 161:172 the pathogenesis 157:172 the pathogenesis of Alzheimer's disease (AD) 157:200 Mechanistic link of protein hypo-O-GlcNAcylation to the pathogenesis of Alzheimer's disease (AD) remains unclear. 26854602 0 31 theme pathogenic 12:21 arg1 induction 23:31 Aβ-affected pathogenic induction 0:31 Aβ-affected pathogenic induction of S-nitrosylation of OGT 0:57 Aβ-affected pathogenic induction of S-nitrosylation of OGT and identification of Cys-NO linkage triplet. 26854602 4 32 theme concerted 605:613 arg1 action 615:620 the concerted action 601:620 the concerted action of Aβ-triggered Ca2+ entry into cells and nNOS-catalyzed NO production 601:691 Our results support that underlying mechanism for induction of SNO-OGT comprises the concerted action of Aβ-triggered Ca2+ entry into cells and nNOS-catalyzed NO production. 26854602 6 33 theme tau 837:839 arg1 hypo-O-GlcNAcylation 841:860 SNO-OGT-mediated tau hypo-O-GlcNAcylation 820:860 SNO-OGT-mediated tau hypo-O-GlcNAcylation 820:860 In parallel with SNO-OGT-mediated tau hypo-O-GlcNAcylation, Aβ led to SNO-Akt-mediated GSK3β activation for tau phosphorylation, suggesting that tau hyperphosphorylation is established by synergistic connection between SNO-OGT and GSK3β activation. 26854602 2 34 theme β-amyloid 324:332 arg1 exposure 347:354 β-amyloid peptide (Aβ) exposure 324:354 β-amyloid peptide (Aβ) exposure to SK-N-MC and SK-N-SH human neuroblastoma cells 324:403 Here, we found that S-nitrosylation of O-linked N-acetylglucosaminyltransferase (SNO-OGT) was induced by β-amyloid peptide (Aβ) exposure to SK-N-MC and SK-N-SH human neuroblastoma cells. 26854602 2 35 theme human 379:383 arg1 cells 399:403 SK-N-MC and SK-N-SH human neuroblastoma cells 359:403 cells 399:403 Here, we found that S-nitrosylation of O-linked N-acetylglucosaminyltransferase (SNO-OGT) was induced by β-amyloid peptide (Aβ) exposure to SK-N-MC and SK-N-SH human neuroblastoma cells. 26854602 0 36 theme Aβ-affected 0:10 arg1 induction 23:31 Aβ-affected pathogenic induction 0:31 Aβ-affected pathogenic induction of S-nitrosylation of OGT 0:57 Aβ-affected pathogenic induction of S-nitrosylation of OGT and identification of Cys-NO linkage triplet. 26854602 6 37 theme SNO-OGT-mediated 820:835 arg1 hypo-O-GlcNAcylation 841:860 SNO-OGT-mediated tau hypo-O-GlcNAcylation 820:860 SNO-OGT-mediated tau hypo-O-GlcNAcylation 820:860 In parallel with SNO-OGT-mediated tau hypo-O-GlcNAcylation, Aβ led to SNO-Akt-mediated GSK3β activation for tau phosphorylation, suggesting that tau hyperphosphorylation is established by synergistic connection between SNO-OGT and GSK3β activation. 26854602 7 38 theme DON 1181:1183 arg1 treatment 1185:1193 DON treatment 1181:1193 DON treatment 1181:1193 We also observed that Aβ-neurotoxicity including both reactive oxygen species (ROS) production and cell death was amplified with DON treatment, whereas it was restored by PUGNAc treatment, GlcNH2 treatment or OGT overexpression. 26854602 2 39 theme SK-N-SH 371:377 arg1 cells 399:403 SK-N-MC and SK-N-SH human neuroblastoma cells 359:403 cells 399:403 Here, we found that S-nitrosylation of O-linked N-acetylglucosaminyltransferase (SNO-OGT) was induced by β-amyloid peptide (Aβ) exposure to SK-N-MC and SK-N-SH human neuroblastoma cells. 26854602 8 40 theme Early 1281:1285 arg1 assay 1313:1317 Early time-course Aβ-monitoring assay 1281:1317 Early time-course Aβ-monitoring assay 1281:1317 Early time-course Aβ-monitoring assay revealed that premaintained hyper-O-GlcNAcylation inside cells blocked not only Aβ-triggered Ca2+ entry into cells but also induction of SNO-OGT and SNO-Akt. 26854602 1 41 theme Mechanistic 105:115 arg1 link 117:120 Mechanistic link 105:120 Mechanistic link of protein hypo-O-GlcNAcylation to the pathogenesis of Alzheimer's disease (AD) 105:200 Mechanistic link of protein hypo-O-GlcNAcylation to the pathogenesis of Alzheimer's disease (AD) remains unclear. 26854602 10 42 theme oxide 1806:1810 arg1 linkages 1821:1828 cysteine-nitric oxide (Cys-NO) linkages 1790:1828 cysteine-nitric oxide (Cys-NO) linkages in SNO-OGT 1790:1839 Furthermore, our Cys mapping demonstrates that cysteine-nitric oxide (Cys-NO) linkages in SNO-OGT occur at triple Cys845, Cys921, and Cys965 residues in C-terminal catalytic domain (C-CAT), suggesting that Cys-NO linkage triplet in SNO-OGT is associated with null OGT activity. 26854602 7 43 theme GlcNH2 1241:1246 arg1 treatment 1248:1256 GlcNH2 treatment 1241:1256 GlcNH2 treatment 1241:1256 We also observed that Aβ-neurotoxicity including both reactive oxygen species (ROS) production and cell death was amplified with DON treatment, whereas it was restored by PUGNAc treatment, GlcNH2 treatment or OGT overexpression. 26854602 9 44 theme Aβ 1539:1540 arg1 exposure 1542:1549 Aβ exposure 1539:1549 Aβ exposure 1539:1549 Together, these findings suggest that induction of SNO-OGT by Aβ exposure is a pathogenic mechanism to cause cellular hypo-O-GlcNAcylation by which Aβ neurotoxicity is executed, and conversely, hyper-O-GlcNAcylation within cells can defend against Aβ neurotoxicity. 26854602 3 45 theme tau 494:496 arg1 hypo-O-GlcNAcylation 498:517 tau hypo-O-GlcNAcylation 494:517 tau hypo-O-GlcNAcylation 494:517 Subsequently, Aβ-induced SNO-OGT led to protein hypo-O-GlcNAcylation globally including tau hypo-O-GlcNAcylation. 26854602 7 46 theme PUGNAc 1223:1228 arg1 treatment 1230:1238 PUGNAc treatment 1223:1238 PUGNAc treatment 1223:1238 We also observed that Aβ-neurotoxicity including both reactive oxygen species (ROS) production and cell death was amplified with DON treatment, whereas it was restored by PUGNAc treatment, GlcNH2 treatment or OGT overexpression. 26854602 2 47 theme Aβ 343:344 arg1 exposure 347:354 β-amyloid peptide (Aβ) exposure 324:354 β-amyloid peptide (Aβ) exposure to SK-N-MC and SK-N-SH human neuroblastoma cells 324:403 Here, we found that S-nitrosylation of O-linked N-acetylglucosaminyltransferase (SNO-OGT) was induced by β-amyloid peptide (Aβ) exposure to SK-N-MC and SK-N-SH human neuroblastoma cells. 26854602 8 48 theme hyper-O-GlcNAcylation 1347:1367 arg1 cells 1376:1380 premaintained hyper-O-GlcNAcylation inside cells 1333:1380 premaintained hyper-O-GlcNAcylation inside cells 1333:1380 Early time-course Aβ-monitoring assay revealed that premaintained hyper-O-GlcNAcylation inside cells blocked not only Aβ-triggered Ca2+ entry into cells but also induction of SNO-OGT and SNO-Akt. 26854602 10 49 theme C-terminal 1896:1905 arg1 C-CAT 1925:1929 C-CAT 1925:1929 C-CAT 1925:1929 Furthermore, our Cys mapping demonstrates that cysteine-nitric oxide (Cys-NO) linkages in SNO-OGT occur at triple Cys845, Cys921, and Cys965 residues in C-terminal catalytic domain (C-CAT), suggesting that Cys-NO linkage triplet in SNO-OGT is associated with null OGT activity. 26854602 10 49 theme C-terminal 1896:1905 arg1 domain 1917:1922 C-terminal catalytic domain 1896:1922 C-terminal catalytic domain (C-CAT) 1896:1930 Furthermore, our Cys mapping demonstrates that cysteine-nitric oxide (Cys-NO) linkages in SNO-OGT occur at triple Cys845, Cys921, and Cys965 residues in C-terminal catalytic domain (C-CAT), suggesting that Cys-NO linkage triplet in SNO-OGT is associated with null OGT activity. 26854602 0 50 theme S-nitrosylation 36:50 arg1 induction 23:31 Aβ-affected pathogenic induction 0:31 Aβ-affected pathogenic induction of S-nitrosylation of OGT 0:57 Aβ-affected pathogenic induction of S-nitrosylation of OGT and identification of Cys-NO linkage triplet. 26854602 0 50 theme S-nitrosylation 36:50 arg1 identification 63:76 identification 63:76 identification of Cys-NO linkage triplet 63:102 Aβ-affected pathogenic induction of S-nitrosylation of OGT and identification of Cys-NO linkage triplet. 26854602 6 51 theme GSK3β 1034:1038 arg1 activation 1040:1049 GSK3β activation 1034:1049 GSK3β activation 1034:1049 In parallel with SNO-OGT-mediated tau hypo-O-GlcNAcylation, Aβ led to SNO-Akt-mediated GSK3β activation for tau phosphorylation, suggesting that tau hyperphosphorylation is established by synergistic connection between SNO-OGT and GSK3β activation. 26854602 3 52 theme Aβ-induced 420:429 arg1 SNO-OGT 431:437 Aβ-induced SNO-OGT 420:437 Aβ-induced SNO-OGT 420:437 Subsequently, Aβ-induced SNO-OGT led to protein hypo-O-GlcNAcylation globally including tau hypo-O-GlcNAcylation. 26854602 9 53 theme Aβ 1725:1726 arg1 neurotoxicity 1728:1740 Aβ neurotoxicity 1725:1740 Aβ neurotoxicity 1725:1740 Together, these findings suggest that induction of SNO-OGT by Aβ exposure is a pathogenic mechanism to cause cellular hypo-O-GlcNAcylation by which Aβ neurotoxicity is executed, and conversely, hyper-O-GlcNAcylation within cells can defend against Aβ neurotoxicity. 26854602 7 54 theme oxygen 1115:1120 arg1 ROS 1131:1133 ROS 1131:1133 ROS 1131:1133 We also observed that Aβ-neurotoxicity including both reactive oxygen species (ROS) production and cell death was amplified with DON treatment, whereas it was restored by PUGNAc treatment, GlcNH2 treatment or OGT overexpression. 26854602 7 54 theme oxygen 1115:1120 arg1 species 1122:1128 reactive oxygen species 1106:1128 reactive oxygen species (ROS) production 1106:1145 We also observed that Aβ-neurotoxicity including both reactive oxygen species (ROS) production and cell death was amplified with DON treatment, whereas it was restored by PUGNAc treatment, GlcNH2 treatment or OGT overexpression. 26854602 9 55 theme cellular 1586:1593 arg1 hypo-O-GlcNAcylation 1595:1614 cellular hypo-O-GlcNAcylation 1586:1614 cellular hypo-O-GlcNAcylation by which Aβ neurotoxicity is executed 1586:1652 Together, these findings suggest that induction of SNO-OGT by Aβ exposure is a pathogenic mechanism to cause cellular hypo-O-GlcNAcylation by which Aβ neurotoxicity is executed, and conversely, hyper-O-GlcNAcylation within cells can defend against Aβ neurotoxicity. 26854602 10 56 theme Cys845 1857:1862 arg1 residues 1884:1891 triple Cys845, Cys921, and Cys965 residues 1850:1891 triple Cys845, Cys921, and Cys965 residues in C-terminal catalytic domain (C-CAT) 1850:1930 Furthermore, our Cys mapping demonstrates that cysteine-nitric oxide (Cys-NO) linkages in SNO-OGT occur at triple Cys845, Cys921, and Cys965 residues in C-terminal catalytic domain (C-CAT), suggesting that Cys-NO linkage triplet in SNO-OGT is associated with null OGT activity. 26854602 8 57 theme time-course 1287:1297 arg1 assay 1313:1317 Early time-course Aβ-monitoring assay 1281:1317 Early time-course Aβ-monitoring assay 1281:1317 Early time-course Aβ-monitoring assay revealed that premaintained hyper-O-GlcNAcylation inside cells blocked not only Aβ-triggered Ca2+ entry into cells but also induction of SNO-OGT and SNO-Akt. 26854602 6 58 theme tau 911:913 arg1 phosphorylation 915:929 tau phosphorylation 911:929 tau phosphorylation 911:929 In parallel with SNO-OGT-mediated tau hypo-O-GlcNAcylation, Aβ led to SNO-Akt-mediated GSK3β activation for tau phosphorylation, suggesting that tau hyperphosphorylation is established by synergistic connection between SNO-OGT and GSK3β activation. 26854602 7 59 theme species 1122:1128 arg1 production 1136:1145 reactive oxygen species (ROS) production 1106:1145 reactive oxygen species (ROS) production 1106:1145 We also observed that Aβ-neurotoxicity including both reactive oxygen species (ROS) production and cell death was amplified with DON treatment, whereas it was restored by PUGNAc treatment, GlcNH2 treatment or OGT overexpression. 26854602 7 60 theme cell 1151:1154 arg1 death 1156:1160 cell death 1151:1160 cell death 1151:1160 We also observed that Aβ-neurotoxicity including both reactive oxygen species (ROS) production and cell death was amplified with DON treatment, whereas it was restored by PUGNAc treatment, GlcNH2 treatment or OGT overexpression. 26854602 0 61 theme OGT 55:57 arg1 S-nitrosylation 36:50 S-nitrosylation 36:50 S-nitrosylation of OGT 36:57 Aβ-affected pathogenic induction of S-nitrosylation of OGT and identification of Cys-NO linkage triplet. 26854602 4 62 theme SNO-OGT 583:589 arg1 induction 570:578 induction 570:578 induction of SNO-OGT 570:589 Our results support that underlying mechanism for induction of SNO-OGT comprises the concerted action of Aβ-triggered Ca2+ entry into cells and nNOS-catalyzed NO production. 26854602 10 63 theme null 2002:2005 arg1 activity 2011:2018 null OGT activity 2002:2018 null OGT activity 2002:2018 Furthermore, our Cys mapping demonstrates that cysteine-nitric oxide (Cys-NO) linkages in SNO-OGT occur at triple Cys845, Cys921, and Cys965 residues in C-terminal catalytic domain (C-CAT), suggesting that Cys-NO linkage triplet in SNO-OGT is associated with null OGT activity. 26854602 8 64 theme inside 1369:1374 arg1 cells 1376:1380 premaintained hyper-O-GlcNAcylation inside cells 1333:1380 premaintained hyper-O-GlcNAcylation inside cells 1333:1380 Early time-course Aβ-monitoring assay revealed that premaintained hyper-O-GlcNAcylation inside cells blocked not only Aβ-triggered Ca2+ entry into cells but also induction of SNO-OGT and SNO-Akt. 26854602 1 65 theme protein 125:131 arg1 hypo-O-GlcNAcylation 133:152 protein hypo-O-GlcNAcylation 125:152 protein hypo-O-GlcNAcylation 125:152 Mechanistic link of protein hypo-O-GlcNAcylation to the pathogenesis of Alzheimer's disease (AD) remains unclear. 26854602 10 66 theme Cys 1760:1762 arg1 mapping 1764:1770 our Cys mapping 1756:1770 our Cys mapping 1756:1770 Furthermore, our Cys mapping demonstrates that cysteine-nitric oxide (Cys-NO) linkages in SNO-OGT occur at triple Cys845, Cys921, and Cys965 residues in C-terminal catalytic domain (C-CAT), suggesting that Cys-NO linkage triplet in SNO-OGT is associated with null OGT activity. 26854602 10 67 theme Cys-NO 1949:1954 arg1 triplet 1964:1970 Cys-NO linkage triplet 1949:1970 Cys-NO linkage triplet in SNO-OGT 1949:1981 Furthermore, our Cys mapping demonstrates that cysteine-nitric oxide (Cys-NO) linkages in SNO-OGT occur at triple Cys845, Cys921, and Cys965 residues in C-terminal catalytic domain (C-CAT), suggesting that Cys-NO linkage triplet in SNO-OGT is associated with null OGT activity. 26854602 2 68 theme O-linked 258:265 arg1 SNO-OGT 300:306 SNO-OGT 300:306 SNO-OGT 300:306 Here, we found that S-nitrosylation of O-linked N-acetylglucosaminyltransferase (SNO-OGT) was induced by β-amyloid peptide (Aβ) exposure to SK-N-MC and SK-N-SH human neuroblastoma cells. 26854602 2 68 theme O-linked 258:265 arg1 N-acetylglucosaminyltransferase 267:297 O-linked N-acetylglucosaminyltransferase 258:297 O-linked N-acetylglucosaminyltransferase (SNO-OGT) 258:307 Here, we found that S-nitrosylation of O-linked N-acetylglucosaminyltransferase (SNO-OGT) was induced by β-amyloid peptide (Aβ) exposure to SK-N-MC and SK-N-SH human neuroblastoma cells. 26854602 7 69 theme reactive 1106:1113 arg1 ROS 1131:1133 ROS 1131:1133 ROS 1131:1133 We also observed that Aβ-neurotoxicity including both reactive oxygen species (ROS) production and cell death was amplified with DON treatment, whereas it was restored by PUGNAc treatment, GlcNH2 treatment or OGT overexpression. 26854602 7 69 theme reactive 1106:1113 arg1 species 1122:1128 reactive oxygen species 1106:1128 reactive oxygen species (ROS) production 1106:1145 We also observed that Aβ-neurotoxicity including both reactive oxygen species (ROS) production and cell death was amplified with DON treatment, whereas it was restored by PUGNAc treatment, GlcNH2 treatment or OGT overexpression. 26854602 1 70 theme hypo-O-GlcNAcylation 133:152 arg1 link 117:120 Mechanistic link 105:120 Mechanistic link of protein hypo-O-GlcNAcylation to the pathogenesis of Alzheimer's disease (AD) 105:200 Mechanistic link of protein hypo-O-GlcNAcylation to the pathogenesis of Alzheimer's disease (AD) remains unclear. 26854602 10 71 theme Cys921 1865:1870 arg1 residues 1884:1891 triple Cys845, Cys921, and Cys965 residues 1850:1891 triple Cys845, Cys921, and Cys965 residues in C-terminal catalytic domain (C-CAT) 1850:1930 Furthermore, our Cys mapping demonstrates that cysteine-nitric oxide (Cys-NO) linkages in SNO-OGT occur at triple Cys845, Cys921, and Cys965 residues in C-terminal catalytic domain (C-CAT), suggesting that Cys-NO linkage triplet in SNO-OGT is associated with null OGT activity. 26854602 6 72 theme GSK3β 890:894 arg1 activation 896:905 SNO-Akt-mediated GSK3β activation 873:905 SNO-Akt-mediated GSK3β activation for tau phosphorylation 873:929 In parallel with SNO-OGT-mediated tau hypo-O-GlcNAcylation, Aβ led to SNO-Akt-mediated GSK3β activation for tau phosphorylation, suggesting that tau hyperphosphorylation is established by synergistic connection between SNO-OGT and GSK3β activation. 26854602 10 73 theme Cys965 1877:1882 arg1 residues 1884:1891 triple Cys845, Cys921, and Cys965 residues 1850:1891 triple Cys845, Cys921, and Cys965 residues in C-terminal catalytic domain (C-CAT) 1850:1930 Furthermore, our Cys mapping demonstrates that cysteine-nitric oxide (Cys-NO) linkages in SNO-OGT occur at triple Cys845, Cys921, and Cys965 residues in C-terminal catalytic domain (C-CAT), suggesting that Cys-NO linkage triplet in SNO-OGT is associated with null OGT activity. 26854602 2 74 theme peptide 334:340 arg1 exposure 347:354 β-amyloid peptide (Aβ) exposure 324:354 β-amyloid peptide (Aβ) exposure to SK-N-MC and SK-N-SH human neuroblastoma cells 324:403 Here, we found that S-nitrosylation of O-linked N-acetylglucosaminyltransferase (SNO-OGT) was induced by β-amyloid peptide (Aβ) exposure to SK-N-MC and SK-N-SH human neuroblastoma cells. 26854602 10 75 theme catalytic 1907:1915 arg1 C-CAT 1925:1929 C-CAT 1925:1929 C-CAT 1925:1929 Furthermore, our Cys mapping demonstrates that cysteine-nitric oxide (Cys-NO) linkages in SNO-OGT occur at triple Cys845, Cys921, and Cys965 residues in C-terminal catalytic domain (C-CAT), suggesting that Cys-NO linkage triplet in SNO-OGT is associated with null OGT activity. 26854602 10 75 theme catalytic 1907:1915 arg1 domain 1917:1922 C-terminal catalytic domain 1896:1922 C-terminal catalytic domain (C-CAT) 1896:1930 Furthermore, our Cys mapping demonstrates that cysteine-nitric oxide (Cys-NO) linkages in SNO-OGT occur at triple Cys845, Cys921, and Cys965 residues in C-terminal catalytic domain (C-CAT), suggesting that Cys-NO linkage triplet in SNO-OGT is associated with null OGT activity. 26854602 10 76 from triplet 1964:1970 arg1 SNO-OGT 1975:1981 SNO-OGT 1975:1981 SNO-OGT 1975:1981 Furthermore, our Cys mapping demonstrates that cysteine-nitric oxide (Cys-NO) linkages in SNO-OGT occur at triple Cys845, Cys921, and Cys965 residues in C-terminal catalytic domain (C-CAT), suggesting that Cys-NO linkage triplet in SNO-OGT is associated with null OGT activity. 26854602 6 77 theme SNO-Akt-mediated 873:888 arg1 activation 896:905 SNO-Akt-mediated GSK3β activation 873:905 SNO-Akt-mediated GSK3β activation for tau phosphorylation 873:929 In parallel with SNO-OGT-mediated tau hypo-O-GlcNAcylation, Aβ led to SNO-Akt-mediated GSK3β activation for tau phosphorylation, suggesting that tau hyperphosphorylation is established by synergistic connection between SNO-OGT and GSK3β activation. 26854602 3 78 theme protein 446:452 arg1 hypo-O-GlcNAcylation 454:473 protein hypo-O-GlcNAcylation 446:473 protein hypo-O-GlcNAcylation globally including tau hypo-O-GlcNAcylation 446:517 Subsequently, Aβ-induced SNO-OGT led to protein hypo-O-GlcNAcylation globally including tau hypo-O-GlcNAcylation. 26854602 4 79 theme nNOS-catalyzed 664:677 arg1 production 682:691 nNOS-catalyzed NO production 664:691 nNOS-catalyzed NO production 664:691 Our results support that underlying mechanism for induction of SNO-OGT comprises the concerted action of Aβ-triggered Ca2+ entry into cells and nNOS-catalyzed NO production. 26854602 4 80 theme entry 643:647 arg1 action 615:620 the concerted action 601:620 the concerted action of Aβ-triggered Ca2+ entry into cells and nNOS-catalyzed NO production 601:691 Our results support that underlying mechanism for induction of SNO-OGT comprises the concerted action of Aβ-triggered Ca2+ entry into cells and nNOS-catalyzed NO production. 26854602 2 81 theme SK-N-MC 359:365 arg1 cells 399:403 SK-N-MC and SK-N-SH human neuroblastoma cells 359:403 cells 399:403 Here, we found that S-nitrosylation of O-linked N-acetylglucosaminyltransferase (SNO-OGT) was induced by β-amyloid peptide (Aβ) exposure to SK-N-MC and SK-N-SH human neuroblastoma cells. 26100231 0 0 theme human 84:88 arg1 cells 105:109 human embryonic stem cells 84:109 human embryonic stem cells 84:109 RING1B O-GlcNAcylation regulates gene targeting of polycomb repressive complex 1 in human embryonic stem cells. 26100231 7 1 theme neuronal 1161:1168 arg1 genes 1170:1174 neuronal genes 1161:1174 neuronal genes 1161:1174 Non-O-GlcNAcylated RING1B is found to be enriched near cell cycle genes whereas O-GlcNAcylated RING1B seems preferentially enriched near neuronal genes. 26100231 4 2 theme major 678:682 arg1 repressor 695:703 a major epigenetic repressor 676:703 the polycomb repressive complex 1 (PRC1) a major epigenetic repressor essential for pluripotency maintenance and differentiation 635:762 Thereafter, we focused our work on RING1B which is the catalytic subunit of the polycomb repressive complex 1 (PRC1) a major epigenetic repressor essential for pluripotency maintenance and differentiation. 26100231 0 3 theme stem 100:103 arg1 cells 105:109 human embryonic stem cells 84:109 human embryonic stem cells 84:109 RING1B O-GlcNAcylation regulates gene targeting of polycomb repressive complex 1 in human embryonic stem cells. 26100231 2 4 theme cells 318:322 arg1 differentiation 331:345 human embryonic stem cells (hESC) differentiation 297:345 human embryonic stem cells (hESC) differentiation 297:345 Recently, O-GlcNAc has been linked to human embryonic stem cells (hESC) differentiation, however the identity and function of O-GlcNAc proteins regulating hESC remain unknown. 26100231 6 5 theme RING1B-DNA 960:969 arg1 binding 971:977 RING1B-DNA binding 960:977 RING1B-DNA binding 960:977 O-GlcNAc seems to regulate RING1B-DNA binding as suggested by our ChIP-sequencing results. 26100231 0 6 theme embryonic 90:98 arg1 cells 105:109 human embryonic stem cells 84:109 human embryonic stem cells 84:109 RING1B O-GlcNAcylation regulates gene targeting of polycomb repressive complex 1 in human embryonic stem cells. 26100231 2 7 theme stem 313:316 arg1 hESC 325:328 hESC 325:328 hESC 325:328 Recently, O-GlcNAc has been linked to human embryonic stem cells (hESC) differentiation, however the identity and function of O-GlcNAc proteins regulating hESC remain unknown. 26100231 2 7 theme stem 313:316 arg1 cells 318:322 human embryonic stem cells 297:322 human embryonic stem cells (hESC) differentiation 297:345 Recently, O-GlcNAc has been linked to human embryonic stem cells (hESC) differentiation, however the identity and function of O-GlcNAc proteins regulating hESC remain unknown. 26100231 4 8 theme polycomb 639:646 arg1 complex 659:665 polycomb repressive complex 1 639:667 the polycomb repressive complex 1 (PRC1) a major epigenetic repressor essential for pluripotency maintenance and differentiation 635:762 Thereafter, we focused our work on RING1B which is the catalytic subunit of the polycomb repressive complex 1 (PRC1) a major epigenetic repressor essential for pluripotency maintenance and differentiation. 26100231 4 8 theme polycomb 639:646 arg1 PRC1 670:673 PRC1 670:673 PRC1 670:673 Thereafter, we focused our work on RING1B which is the catalytic subunit of the polycomb repressive complex 1 (PRC1) a major epigenetic repressor essential for pluripotency maintenance and differentiation. 26100231 7 9 theme Non-O-GlcNAcylated 1024:1041 arg1 RING1B 1043:1048 Non-O-GlcNAcylated RING1B 1024:1048 Non-O-GlcNAcylated RING1B 1024:1048 Non-O-GlcNAcylated RING1B is found to be enriched near cell cycle genes whereas O-GlcNAcylated RING1B seems preferentially enriched near neuronal genes. 26100231 3 10 theme cell 492:495 arg1 RING1B/RNF2 546:556 RING1B/RNF2 546:556 RING1B/RNF2 546:556 Here, we firstly identified O-GlcNAc modified human stem cell regulators such as hnRNP K, HP1γ, and especially RING1B/RNF2. 26100231 3 10 theme cell 492:495 arg1 regulators 497:506 O-GlcNAc modified human stem cell regulators 463:506 O-GlcNAc modified human stem cell regulators such as hnRNP K, HP1γ, and especially RING1B/RNF2 463:556 Here, we firstly identified O-GlcNAc modified human stem cell regulators such as hnRNP K, HP1γ, and especially RING1B/RNF2. 26100231 3 10 theme cell 492:495 arg1 HP1γ 525:528 HP1γ 525:528 HP1γ 525:528 Here, we firstly identified O-GlcNAc modified human stem cell regulators such as hnRNP K, HP1γ, and especially RING1B/RNF2. 26100231 3 10 theme cell 492:495 arg1 K 522:522 hnRNP K 516:522 hnRNP K 516:522 Here, we firstly identified O-GlcNAc modified human stem cell regulators such as hnRNP K, HP1γ, and especially RING1B/RNF2. 26100231 2 11 theme embryonic 303:311 arg1 hESC 325:328 hESC 325:328 hESC 325:328 Recently, O-GlcNAc has been linked to human embryonic stem cells (hESC) differentiation, however the identity and function of O-GlcNAc proteins regulating hESC remain unknown. 26100231 2 11 theme embryonic 303:311 arg1 cells 318:322 human embryonic stem cells 297:322 human embryonic stem cells (hESC) differentiation 297:345 Recently, O-GlcNAc has been linked to human embryonic stem cells (hESC) differentiation, however the identity and function of O-GlcNAc proteins regulating hESC remain unknown. 26100231 9 12 theme essential 1404:1412 arg1 RING1B 1431:1436 RING1B 1431:1436 RING1B 1431:1436 Overall, we demonstrate that O-GlcNAc modifies and regulates an essential epigenetic tool, RING1B, which may contribute to hESC pluripotency maintenance and differentiation. 26100231 9 12 theme essential 1404:1412 arg1 tool 1425:1428 an essential epigenetic tool 1401:1428 an essential epigenetic tool 1401:1428 Overall, we demonstrate that O-GlcNAc modifies and regulates an essential epigenetic tool, RING1B, which may contribute to hESC pluripotency maintenance and differentiation. 26100231 4 13 theme complex 659:665 arg1 subunit 624:630 the catalytic subunit 610:630 the catalytic subunit of the polycomb repressive complex 1 (PRC1) a major epigenetic repressor essential for pluripotency maintenance and differentiation 610:762 Thereafter, we focused our work on RING1B which is the catalytic subunit of the polycomb repressive complex 1 (PRC1) a major epigenetic repressor essential for pluripotency maintenance and differentiation. 26100231 4 13 theme complex 659:665 arg1 RING1B 594:599 RING1B 594:599 RING1B which is the catalytic subunit of the polycomb repressive complex 1 (PRC1) a major epigenetic repressor essential for pluripotency maintenance and differentiation 594:762 Thereafter, we focused our work on RING1B which is the catalytic subunit of the polycomb repressive complex 1 (PRC1) a major epigenetic repressor essential for pluripotency maintenance and differentiation. 26100231 5 14 theme T 797:797 arg1 residues 829:836 T(250)/S(251) and S(278) RING1B residues 797:836 T(250)/S(251) and S(278) RING1B residues 797:836 By point-mutation, we show that T(250)/S(251) and S(278) RING1B residues are bearing O-GlcNAc, and that T(250)/S(251) O-GlcNAcylation decreases during differentiation. 26100231 2 15 theme human 297:301 arg1 hESC 325:328 hESC 325:328 hESC 325:328 Recently, O-GlcNAc has been linked to human embryonic stem cells (hESC) differentiation, however the identity and function of O-GlcNAc proteins regulating hESC remain unknown. 26100231 2 15 theme human 297:301 arg1 cells 318:322 human embryonic stem cells 297:322 human embryonic stem cells (hESC) differentiation 297:345 Recently, O-GlcNAc has been linked to human embryonic stem cells (hESC) differentiation, however the identity and function of O-GlcNAc proteins regulating hESC remain unknown. 26100231 4 16 theme repressive 648:657 arg1 complex 659:665 polycomb repressive complex 1 639:667 the polycomb repressive complex 1 (PRC1) a major epigenetic repressor essential for pluripotency maintenance and differentiation 635:762 Thereafter, we focused our work on RING1B which is the catalytic subunit of the polycomb repressive complex 1 (PRC1) a major epigenetic repressor essential for pluripotency maintenance and differentiation. 26100231 4 16 theme repressive 648:657 arg1 PRC1 670:673 PRC1 670:673 PRC1 670:673 Thereafter, we focused our work on RING1B which is the catalytic subunit of the polycomb repressive complex 1 (PRC1) a major epigenetic repressor essential for pluripotency maintenance and differentiation. 26100231 7 17 theme O-GlcNAcylated 1104:1117 arg1 RING1B 1119:1124 O-GlcNAcylated RING1B 1104:1124 O-GlcNAcylated RING1B 1104:1124 Non-O-GlcNAcylated RING1B is found to be enriched near cell cycle genes whereas O-GlcNAcylated RING1B seems preferentially enriched near neuronal genes. 26100231 0 18 from targeting 38:46 arg1 cells 105:109 human embryonic stem cells 84:109 human embryonic stem cells 84:109 RING1B O-GlcNAcylation regulates gene targeting of polycomb repressive complex 1 in human embryonic stem cells. 26100231 6 19 theme ChIP-sequencing 999:1013 arg1 results 1015:1021 our ChIP-sequencing results 995:1021 our ChIP-sequencing results 995:1021 O-GlcNAc seems to regulate RING1B-DNA binding as suggested by our ChIP-sequencing results. 26100231 5 20 theme T 869:869 arg1 O-GlcNAcylation 883:897 T(250)/S(251) O-GlcNAcylation 869:897 T(250)/S(251) O-GlcNAcylation 869:897 By point-mutation, we show that T(250)/S(251) and S(278) RING1B residues are bearing O-GlcNAc, and that T(250)/S(251) O-GlcNAcylation decreases during differentiation. 26100231 1 21 theme proteins 209:216 arg1 thousands 196:204 thousands 196:204 thousands of proteins involved in various cellular mechanisms 196:256 O-linked-N-acetylglucosamine (O-GlcNAc) post-translationally modifies and regulates thousands of proteins involved in various cellular mechanisms. 26100231 0 22 theme RING1B 0:5 arg1 O-GlcNAcylation 7:21 RING1B O-GlcNAcylation 0:21 RING1B O-GlcNAcylation 0:21 RING1B O-GlcNAcylation regulates gene targeting of polycomb repressive complex 1 in human embryonic stem cells. 26100231 4 23 theme pluripotency 719:730 arg1 maintenance 732:742 pluripotency maintenance 719:742 pluripotency maintenance 719:742 Thereafter, we focused our work on RING1B which is the catalytic subunit of the polycomb repressive complex 1 (PRC1) a major epigenetic repressor essential for pluripotency maintenance and differentiation. 26100231 8 24 theme hESC 1206:1209 arg1 differentiation 1211:1225 hESC differentiation 1206:1225 hESC differentiation 1206:1225 Our data suggest that during hESC differentiation, the decrease of RING1B O-GlcNAcylation might enable PRC1 to switch its target to induce neuron differentiation. 26100231 2 25 theme proteins 394:401 arg1 function 373:380 function 373:380 function 373:380 Recently, O-GlcNAc has been linked to human embryonic stem cells (hESC) differentiation, however the identity and function of O-GlcNAc proteins regulating hESC remain unknown. 26100231 2 25 theme proteins 394:401 arg1 identity 360:367 identity 360:367 identity 360:367 Recently, O-GlcNAc has been linked to human embryonic stem cells (hESC) differentiation, however the identity and function of O-GlcNAc proteins regulating hESC remain unknown. 26100231 0 26 theme gene 33:36 arg1 targeting 38:46 gene targeting 33:46 gene targeting of polycomb repressive complex 1 in human embryonic stem cells 33:109 RING1B O-GlcNAcylation regulates gene targeting of polycomb repressive complex 1 in human embryonic stem cells. 26100231 8 27 theme RING1B 1244:1249 arg1 O-GlcNAcylation 1251:1265 RING1B O-GlcNAcylation 1244:1265 RING1B O-GlcNAcylation 1244:1265 Our data suggest that during hESC differentiation, the decrease of RING1B O-GlcNAcylation might enable PRC1 to switch its target to induce neuron differentiation. 26100231 2 28 dep identity 360:367 arg1 the 356:358 the 356:358 the 356:358 Recently, O-GlcNAc has been linked to human embryonic stem cells (hESC) differentiation, however the identity and function of O-GlcNAc proteins regulating hESC remain unknown. 26100231 3 29 theme stem 487:490 arg1 RING1B/RNF2 546:556 RING1B/RNF2 546:556 RING1B/RNF2 546:556 Here, we firstly identified O-GlcNAc modified human stem cell regulators such as hnRNP K, HP1γ, and especially RING1B/RNF2. 26100231 3 29 theme stem 487:490 arg1 regulators 497:506 O-GlcNAc modified human stem cell regulators 463:506 O-GlcNAc modified human stem cell regulators such as hnRNP K, HP1γ, and especially RING1B/RNF2 463:556 Here, we firstly identified O-GlcNAc modified human stem cell regulators such as hnRNP K, HP1γ, and especially RING1B/RNF2. 26100231 3 29 theme stem 487:490 arg1 HP1γ 525:528 HP1γ 525:528 HP1γ 525:528 Here, we firstly identified O-GlcNAc modified human stem cell regulators such as hnRNP K, HP1γ, and especially RING1B/RNF2. 26100231 3 29 theme stem 487:490 arg1 K 522:522 hnRNP K 516:522 hnRNP K 516:522 Here, we firstly identified O-GlcNAc modified human stem cell regulators such as hnRNP K, HP1γ, and especially RING1B/RNF2. 26100231 8 30 theme neuron 1316:1321 arg1 differentiation 1323:1337 neuron differentiation 1316:1337 neuron differentiation 1316:1337 Our data suggest that during hESC differentiation, the decrease of RING1B O-GlcNAcylation might enable PRC1 to switch its target to induce neuron differentiation. 26100231 1 31 theme various 230:236 arg1 mechanisms 247:256 various cellular mechanisms 230:256 various cellular mechanisms 230:256 O-linked-N-acetylglucosamine (O-GlcNAc) post-translationally modifies and regulates thousands of proteins involved in various cellular mechanisms. 26100231 7 32 theme cell 1079:1082 arg1 genes 1090:1094 cell cycle genes 1079:1094 cell cycle genes 1079:1094 Non-O-GlcNAcylated RING1B is found to be enriched near cell cycle genes whereas O-GlcNAcylated RING1B seems preferentially enriched near neuronal genes. 26100231 4 33 theme epigenetic 684:693 arg1 repressor 695:703 a major epigenetic repressor 676:703 the polycomb repressive complex 1 (PRC1) a major epigenetic repressor essential for pluripotency maintenance and differentiation 635:762 Thereafter, we focused our work on RING1B which is the catalytic subunit of the polycomb repressive complex 1 (PRC1) a major epigenetic repressor essential for pluripotency maintenance and differentiation. 26100231 3 34 theme modified 472:479 arg1 RING1B/RNF2 546:556 RING1B/RNF2 546:556 RING1B/RNF2 546:556 Here, we firstly identified O-GlcNAc modified human stem cell regulators such as hnRNP K, HP1γ, and especially RING1B/RNF2. 26100231 3 34 theme modified 472:479 arg1 regulators 497:506 O-GlcNAc modified human stem cell regulators 463:506 O-GlcNAc modified human stem cell regulators such as hnRNP K, HP1γ, and especially RING1B/RNF2 463:556 Here, we firstly identified O-GlcNAc modified human stem cell regulators such as hnRNP K, HP1γ, and especially RING1B/RNF2. 26100231 3 34 theme modified 472:479 arg1 HP1γ 525:528 HP1γ 525:528 HP1γ 525:528 Here, we firstly identified O-GlcNAc modified human stem cell regulators such as hnRNP K, HP1γ, and especially RING1B/RNF2. 26100231 3 34 theme modified 472:479 arg1 K 522:522 hnRNP K 516:522 hnRNP K 516:522 Here, we firstly identified O-GlcNAc modified human stem cell regulators such as hnRNP K, HP1γ, and especially RING1B/RNF2. 26100231 9 35 theme epigenetic 1414:1423 arg1 RING1B 1431:1436 RING1B 1431:1436 RING1B 1431:1436 Overall, we demonstrate that O-GlcNAc modifies and regulates an essential epigenetic tool, RING1B, which may contribute to hESC pluripotency maintenance and differentiation. 26100231 9 35 theme epigenetic 1414:1423 arg1 tool 1425:1428 an essential epigenetic tool 1401:1428 an essential epigenetic tool 1401:1428 Overall, we demonstrate that O-GlcNAc modifies and regulates an essential epigenetic tool, RING1B, which may contribute to hESC pluripotency maintenance and differentiation. 26100231 1 36 theme cellular 238:245 arg1 mechanisms 247:256 various cellular mechanisms 230:256 various cellular mechanisms 230:256 O-linked-N-acetylglucosamine (O-GlcNAc) post-translationally modifies and regulates thousands of proteins involved in various cellular mechanisms. 26100231 5 37 theme S 815:815 arg1 residues 829:836 T(250)/S(251) and S(278) RING1B residues 797:836 T(250)/S(251) and S(278) RING1B residues 797:836 By point-mutation, we show that T(250)/S(251) and S(278) RING1B residues are bearing O-GlcNAc, and that T(250)/S(251) O-GlcNAcylation decreases during differentiation. 26100231 7 38 theme cycle 1084:1088 arg1 genes 1090:1094 cell cycle genes 1079:1094 cell cycle genes 1079:1094 Non-O-GlcNAcylated RING1B is found to be enriched near cell cycle genes whereas O-GlcNAcylated RING1B seems preferentially enriched near neuronal genes. 26100231 3 39 theme human 481:485 arg1 RING1B/RNF2 546:556 RING1B/RNF2 546:556 RING1B/RNF2 546:556 Here, we firstly identified O-GlcNAc modified human stem cell regulators such as hnRNP K, HP1γ, and especially RING1B/RNF2. 26100231 3 39 theme human 481:485 arg1 regulators 497:506 O-GlcNAc modified human stem cell regulators 463:506 O-GlcNAc modified human stem cell regulators such as hnRNP K, HP1γ, and especially RING1B/RNF2 463:556 Here, we firstly identified O-GlcNAc modified human stem cell regulators such as hnRNP K, HP1γ, and especially RING1B/RNF2. 26100231 3 39 theme human 481:485 arg1 HP1γ 525:528 HP1γ 525:528 HP1γ 525:528 Here, we firstly identified O-GlcNAc modified human stem cell regulators such as hnRNP K, HP1γ, and especially RING1B/RNF2. 26100231 3 39 theme human 481:485 arg1 K 522:522 hnRNP K 516:522 hnRNP K 516:522 Here, we firstly identified O-GlcNAc modified human stem cell regulators such as hnRNP K, HP1γ, and especially RING1B/RNF2. 26100231 0 40 theme repressive 60:69 arg1 complex 71:77 polycomb repressive complex 1 51:79 polycomb repressive complex 1 51:79 RING1B O-GlcNAcylation regulates gene targeting of polycomb repressive complex 1 in human embryonic stem cells. 26100231 5 41 theme RING1B 822:827 arg1 residues 829:836 T(250)/S(251) and S(278) RING1B residues 797:836 T(250)/S(251) and S(278) RING1B residues 797:836 By point-mutation, we show that T(250)/S(251) and S(278) RING1B residues are bearing O-GlcNAc, and that T(250)/S(251) O-GlcNAcylation decreases during differentiation. 26100231 0 42 theme polycomb 51:58 arg1 complex 71:77 polycomb repressive complex 1 51:79 polycomb repressive complex 1 51:79 RING1B O-GlcNAcylation regulates gene targeting of polycomb repressive complex 1 in human embryonic stem cells. 26100231 3 43 theme hnRNP 516:520 arg1 K 522:522 hnRNP K 516:522 hnRNP K 516:522 Here, we firstly identified O-GlcNAc modified human stem cell regulators such as hnRNP K, HP1γ, and especially RING1B/RNF2. 26100231 8 44 theme O-GlcNAcylation 1251:1265 arg1 decrease 1232:1239 the decrease 1228:1239 the decrease of RING1B O-GlcNAcylation 1228:1265 Our data suggest that during hESC differentiation, the decrease of RING1B O-GlcNAcylation might enable PRC1 to switch its target to induce neuron differentiation. 26100231 2 45 attach linked 287:292 arg2 O-GlcNAc 269:276 O-GlcNAc 269:276 O-GlcNAc 269:276 Recently, O-GlcNAc has been linked to human embryonic stem cells (hESC) differentiation, however the identity and function of O-GlcNAc proteins regulating hESC remain unknown. 26100231 2 45 attach linked 287:292 arg1 differentiation 331:345 human embryonic stem cells (hESC) differentiation 297:345 human embryonic stem cells (hESC) differentiation 297:345 Recently, O-GlcNAc has been linked to human embryonic stem cells (hESC) differentiation, however the identity and function of O-GlcNAc proteins regulating hESC remain unknown. 26100231 5 46 theme /S 875:876 arg1 O-GlcNAcylation 883:897 T(250)/S(251) O-GlcNAcylation 869:897 T(250)/S(251) O-GlcNAcylation 869:897 By point-mutation, we show that T(250)/S(251) and S(278) RING1B residues are bearing O-GlcNAc, and that T(250)/S(251) O-GlcNAcylation decreases during differentiation. 26100231 4 47 theme essential 705:713 arg1 repressor 695:703 a major epigenetic repressor 676:703 the polycomb repressive complex 1 (PRC1) a major epigenetic repressor essential for pluripotency maintenance and differentiation 635:762 Thereafter, we focused our work on RING1B which is the catalytic subunit of the polycomb repressive complex 1 (PRC1) a major epigenetic repressor essential for pluripotency maintenance and differentiation. 26100231 4 48 dep complex 659:665 arg1 repressor 695:703 a major epigenetic repressor 676:703 the polycomb repressive complex 1 (PRC1) a major epigenetic repressor essential for pluripotency maintenance and differentiation 635:762 Thereafter, we focused our work on RING1B which is the catalytic subunit of the polycomb repressive complex 1 (PRC1) a major epigenetic repressor essential for pluripotency maintenance and differentiation. 26100231 9 49 theme hESC 1463:1466 arg1 maintenance 1481:1491 hESC pluripotency maintenance 1463:1491 hESC pluripotency maintenance 1463:1491 Overall, we demonstrate that O-GlcNAc modifies and regulates an essential epigenetic tool, RING1B, which may contribute to hESC pluripotency maintenance and differentiation. 26100231 2 50 theme O-GlcNAc 385:392 arg1 proteins 394:401 O-GlcNAc proteins 385:401 O-GlcNAc proteins regulating hESC 385:417 Recently, O-GlcNAc has been linked to human embryonic stem cells (hESC) differentiation, however the identity and function of O-GlcNAc proteins regulating hESC remain unknown. 26100231 4 51 theme catalytic 614:622 arg1 subunit 624:630 the catalytic subunit 610:630 the catalytic subunit of the polycomb repressive complex 1 (PRC1) a major epigenetic repressor essential for pluripotency maintenance and differentiation 610:762 Thereafter, we focused our work on RING1B which is the catalytic subunit of the polycomb repressive complex 1 (PRC1) a major epigenetic repressor essential for pluripotency maintenance and differentiation. 26100231 4 51 theme catalytic 614:622 arg1 RING1B 594:599 RING1B 594:599 RING1B which is the catalytic subunit of the polycomb repressive complex 1 (PRC1) a major epigenetic repressor essential for pluripotency maintenance and differentiation 594:762 Thereafter, we focused our work on RING1B which is the catalytic subunit of the polycomb repressive complex 1 (PRC1) a major epigenetic repressor essential for pluripotency maintenance and differentiation. 26100231 0 52 theme complex 71:77 arg1 targeting 38:46 gene targeting 33:46 gene targeting of polycomb repressive complex 1 in human embryonic stem cells 33:109 RING1B O-GlcNAcylation regulates gene targeting of polycomb repressive complex 1 in human embryonic stem cells. 26100231 9 53 theme pluripotency 1468:1479 arg1 maintenance 1481:1491 hESC pluripotency maintenance 1463:1491 hESC pluripotency maintenance 1463:1491 Overall, we demonstrate that O-GlcNAc modifies and regulates an essential epigenetic tool, RING1B, which may contribute to hESC pluripotency maintenance and differentiation. 24788674 11 0 from levels 1828:1833 arg1 PC 1846:1847 retinal PC 1838:1847 retinal PC 1838:1847 Our results indicated that increased O-GlcNAc modification of p53 was associated with an increase in its protein levels in retinal PC. 24788674 5 1 theme various 851:857 arg1 cells 876:880 various retinal vascular cells 851:880 various retinal vascular cells 851:880 We have recently demonstrated that the level of O-GlcNAc modification in response to high glucose is variable in various retinal vascular cells. 24788674 7 2 from increase 1089:1096 arg1 apoptosis 1101:1109 apoptosis 1101:1109 apoptosis of retinal PC 1101:1123 Here we show that these differences translated into functional changes, with an increase in apoptosis of retinal PC, not just under high glucose but also under treatment with O-GlcNAc modification inducers, PUGNAc and Thiamet-G. 24788674 4 3 theme hyperglycemic 593:605 arg1 condition 607:615 hyperglycemic condition 593:615 hyperglycemic condition 593:615 The O-linked β-N-acetylglucosamine (O-GlcNAc) modification is elevated under hyperglycemic condition, and thus, may present an important molecular modification impacting the hyperglycemia-driven complications of diabetes. 24788674 2 4 theme detrimental 283:293 arg1 effect 295:300 a detrimental effect 281:300 a detrimental effect 281:300 Hyperglycemic conditions have a detrimental effect on many tissues and cell types, especially the retinal vascular cells including early loss of pericytes (PC). 24788674 4 5 link O-linked 520:527 arg1 modification 562:573 The O-linked β-N-acetylglucosamine (O-GlcNAc) modification 516:573 The O-linked β-N-acetylglucosamine (O-GlcNAc) modification 516:573 The O-linked β-N-acetylglucosamine (O-GlcNAc) modification is elevated under hyperglycemic condition, and thus, may present an important molecular modification impacting the hyperglycemia-driven complications of diabetes. 24788674 11 6 from increase 1804:1811 arg1 levels 1828:1833 its protein levels 1816:1833 its protein levels in retinal PC 1816:1847 Our results indicated that increased O-GlcNAc modification of p53 was associated with an increase in its protein levels in retinal PC. 24788674 10 7 theme important 1655:1663 arg1 roles 1665:1669 important roles 1655:1669 important roles in various aspects of cell death processes 1655:1712 We have identified at least 34 of these proteins with important roles in various aspects of cell death processes. 24788674 4 8 theme molecular 653:661 arg1 modification 663:674 an important molecular modification 640:674 an important molecular modification impacting the hyperglycemia-driven complications of diabetes 640:735 The O-linked β-N-acetylglucosamine (O-GlcNAc) modification is elevated under hyperglycemic condition, and thus, may present an important molecular modification impacting the hyperglycemia-driven complications of diabetes. 24788674 9 9 theme target 1489:1494 arg1 proteins 1496:1503 the O-GlcNAc target proteins 1476:1503 the O-GlcNAc target proteins identified here 1476:1519 Among the O-GlcNAc target proteins identified here 115 of them were not previously reported to be target of O-GlcNAc modification. 24788674 7 10 theme PC 1122:1123 arg1 apoptosis 1101:1109 apoptosis 1101:1109 apoptosis of retinal PC 1101:1123 Here we show that these differences translated into functional changes, with an increase in apoptosis of retinal PC, not just under high glucose but also under treatment with O-GlcNAc modification inducers, PUGNAc and Thiamet-G. 24788674 0 11 theme diabetic 114:121 arg1 retinopathy 123:133 diabetic retinopathy 114:133 diabetic retinopathy 114:133 Identification of O-GlcNAc modification targets in mouse retinal pericytes: implication of p53 in pathogenesis of diabetic retinopathy. 24788674 5 12 theme retinal 859:865 arg1 cells 876:880 various retinal vascular cells 851:880 various retinal vascular cells 851:880 We have recently demonstrated that the level of O-GlcNAc modification in response to high glucose is variable in various retinal vascular cells. 24788674 0 13 from implication 76:86 arg1 pathogenesis 98:109 pathogenesis 98:109 pathogenesis of diabetic retinopathy 98:133 Identification of O-GlcNAc modification targets in mouse retinal pericytes: implication of p53 in pathogenesis of diabetic retinopathy. 24788674 11 14 theme retinal 1838:1844 arg1 PC 1846:1847 retinal PC 1838:1847 retinal PC 1838:1847 Our results indicated that increased O-GlcNAc modification of p53 was associated with an increase in its protein levels in retinal PC. 24788674 12 15 theme early 1985:1989 arg1 loss 1991:1994 selective early loss 1975:1994 selective early loss of PC during diabetes 1975:2016 Together our results suggest that post-translational O-GlcNAc modification of p53 and its increased levels may contribute to selective early loss of PC during diabetes. 24788674 6 16 theme endothelial 975:985 arg1 cells 987:991 retinal endothelial cells 967:991 retinal endothelial cells 967:991 Retinal PC responded with the highest increase in O-GlcNAc modification compared to retinal endothelial cells and astrocytes. 24788674 8 17 theme click-It 1307:1314 arg1 chemistry 1316:1324 click-It chemistry 1307:1324 click-It chemistry 1307:1324 To gain insight into the molecular mechanisms involved, we have used click-It chemistry and LC-MS analysis and identified 431 target proteins of O-GlcNAc modification in retinal PC using an alkynyl-modified GlcNAc analog (GlcNAlk). 24788674 5 18 from level 777:781 arg1 response 811:818 response 811:818 response to high glucose 811:834 We have recently demonstrated that the level of O-GlcNAc modification in response to high glucose is variable in various retinal vascular cells. 24788674 2 19 theme Hyperglycemic 251:263 arg1 conditions 265:274 Hyperglycemic conditions 251:274 Hyperglycemic conditions 251:274 Hyperglycemic conditions have a detrimental effect on many tissues and cell types, especially the retinal vascular cells including early loss of pericytes (PC). 24788674 9 20 theme them 1528:1531 arg1 them 1528:1531 them 1528:1531 them 1528:1531 Among the O-GlcNAc target proteins identified here 115 of them were not previously reported to be target of O-GlcNAc modification. 24788674 9 20 theme them 1528:1531 arg1 115 1521:1523 115 1521:1523 115 1521:1523 Among the O-GlcNAc target proteins identified here 115 of them were not previously reported to be target of O-GlcNAc modification. 24788674 4 21 theme hyperglycemia-driven 690:709 arg1 complications 711:723 the hyperglycemia-driven complications 686:723 the hyperglycemia-driven complications of diabetes 686:735 The O-linked β-N-acetylglucosamine (O-GlcNAc) modification is elevated under hyperglycemic condition, and thus, may present an important molecular modification impacting the hyperglycemia-driven complications of diabetes. 24788674 11 22 theme O-GlcNAc 1752:1759 arg1 modification 1761:1772 increased O-GlcNAc modification 1742:1772 increased O-GlcNAc modification of p53 1742:1779 Our results indicated that increased O-GlcNAc modification of p53 was associated with an increase in its protein levels in retinal PC. 24788674 13 23 theme treatment 2081:2089 arg1 strategy 2091:2098 a novel treatment strategy 2073:2098 a novel treatment strategy to prevent the initiation and progression of DR 2073:2146 Thus, modulation of O-GlcNAc modification may provide a novel treatment strategy to prevent the initiation and progression of DR. 24788674 7 24 theme O-GlcNAc 1184:1191 arg1 Thiamet-G 1227:1235 Thiamet-G 1227:1235 Thiamet-G 1227:1235 Here we show that these differences translated into functional changes, with an increase in apoptosis of retinal PC, not just under high glucose but also under treatment with O-GlcNAc modification inducers, PUGNAc and Thiamet-G. 24788674 7 24 theme O-GlcNAc 1184:1191 arg1 PUGNAc 1216:1221 PUGNAc 1216:1221 PUGNAc 1216:1221 Here we show that these differences translated into functional changes, with an increase in apoptosis of retinal PC, not just under high glucose but also under treatment with O-GlcNAc modification inducers, PUGNAc and Thiamet-G. 24788674 7 24 theme O-GlcNAc 1184:1191 arg1 inducers 1206:1213 O-GlcNAc modification inducers 1184:1213 O-GlcNAc modification inducers 1184:1213 Here we show that these differences translated into functional changes, with an increase in apoptosis of retinal PC, not just under high glucose but also under treatment with O-GlcNAc modification inducers, PUGNAc and Thiamet-G. 24788674 5 25 theme modification 795:806 arg1 variable 839:846 variable 839:846 variable in various retinal vascular cells 839:880 We have recently demonstrated that the level of O-GlcNAc modification in response to high glucose is variable in various retinal vascular cells. 24788674 5 25 theme modification 795:806 arg1 level 777:781 the level 773:781 the level of O-GlcNAc modification in response to high glucose 773:834 We have recently demonstrated that the level of O-GlcNAc modification in response to high glucose is variable in various retinal vascular cells. 24788674 8 26 theme target 1364:1369 arg1 proteins 1371:1378 431 target proteins 1360:1378 431 target proteins of O-GlcNAc modification 1360:1403 To gain insight into the molecular mechanisms involved, we have used click-It chemistry and LC-MS analysis and identified 431 target proteins of O-GlcNAc modification in retinal PC using an alkynyl-modified GlcNAc analog (GlcNAlk). 24788674 0 27 theme p53 91:93 arg1 implication 76:86 implication 76:86 implication of p53 in pathogenesis of diabetic retinopathy 76:133 Identification of O-GlcNAc modification targets in mouse retinal pericytes: implication of p53 in pathogenesis of diabetic retinopathy. 24788674 5 28 from variable 839:846 arg1 cells 876:880 various retinal vascular cells 851:880 various retinal vascular cells 851:880 We have recently demonstrated that the level of O-GlcNAc modification in response to high glucose is variable in various retinal vascular cells. 24788674 12 29 theme levels 1950:1955 arg1 modification 1912:1923 post-translational O-GlcNAc modification 1884:1923 post-translational O-GlcNAc modification of p53 and its increased levels 1884:1955 Together our results suggest that post-translational O-GlcNAc modification of p53 and its increased levels may contribute to selective early loss of PC during diabetes. 24788674 8 30 theme modification 1392:1403 arg1 proteins 1371:1378 431 target proteins 1360:1378 431 target proteins of O-GlcNAc modification 1360:1403 To gain insight into the molecular mechanisms involved, we have used click-It chemistry and LC-MS analysis and identified 431 target proteins of O-GlcNAc modification in retinal PC using an alkynyl-modified GlcNAc analog (GlcNAlk). 24788674 6 31 theme highest 913:919 arg1 increase 921:928 the highest increase 909:928 the highest increase in O-GlcNAc modification 909:953 Retinal PC responded with the highest increase in O-GlcNAc modification compared to retinal endothelial cells and astrocytes. 24788674 2 32 theme early 382:386 arg1 loss 388:391 early loss 382:391 early loss of pericytes (PC) 382:409 Hyperglycemic conditions have a detrimental effect on many tissues and cell types, especially the retinal vascular cells including early loss of pericytes (PC). 24788674 2 33 contain have 276:279 arg2 effect 295:300 a detrimental effect 281:300 a detrimental effect 281:300 Hyperglycemic conditions have a detrimental effect on many tissues and cell types, especially the retinal vascular cells including early loss of pericytes (PC). 24788674 2 33 contain have 276:279 arg1 conditions 265:274 Hyperglycemic conditions 251:274 Hyperglycemic conditions 251:274 Hyperglycemic conditions have a detrimental effect on many tissues and cell types, especially the retinal vascular cells including early loss of pericytes (PC). 24788674 12 34 theme p53 1928:1930 arg1 modification 1912:1923 post-translational O-GlcNAc modification 1884:1923 post-translational O-GlcNAc modification of p53 and its increased levels 1884:1955 Together our results suggest that post-translational O-GlcNAc modification of p53 and its increased levels may contribute to selective early loss of PC during diabetes. 24788674 9 35 theme modification 1587:1598 arg1 target 1568:1573 target 1568:1573 target of O-GlcNAc modification 1568:1598 Among the O-GlcNAc target proteins identified here 115 of them were not previously reported to be target of O-GlcNAc modification. 24788674 8 36 theme retinal 1408:1414 arg1 PC 1416:1417 retinal PC 1408:1417 retinal PC using an alkynyl-modified GlcNAc analog (GlcNAlk) 1408:1467 To gain insight into the molecular mechanisms involved, we have used click-It chemistry and LC-MS analysis and identified 431 target proteins of O-GlcNAc modification in retinal PC using an alkynyl-modified GlcNAc analog (GlcNAlk). 24788674 10 37 theme cell 1693:1696 arg1 processes 1704:1712 cell death processes 1693:1712 cell death processes 1693:1712 We have identified at least 34 of these proteins with important roles in various aspects of cell death processes. 24788674 0 38 theme O-GlcNAc 18:25 arg1 modification 27:38 O-GlcNAc modification 18:38 O-GlcNAc modification 18:38 Identification of O-GlcNAc modification targets in mouse retinal pericytes: implication of p53 in pathogenesis of diabetic retinopathy. 24788674 12 39 theme post-translational 1884:1901 arg1 modification 1912:1923 post-translational O-GlcNAc modification 1884:1923 post-translational O-GlcNAc modification of p53 and its increased levels 1884:1955 Together our results suggest that post-translational O-GlcNAc modification of p53 and its increased levels may contribute to selective early loss of PC during diabetes. 24788674 6 40 theme Retinal 883:889 arg1 PC 891:892 Retinal PC 883:892 Retinal PC 883:892 Retinal PC responded with the highest increase in O-GlcNAc modification compared to retinal endothelial cells and astrocytes. 24788674 8 41 theme alkynyl-modified 1428:1443 arg1 analog 1452:1457 an alkynyl-modified GlcNAc analog 1425:1457 an alkynyl-modified GlcNAc analog (GlcNAlk) 1425:1467 To gain insight into the molecular mechanisms involved, we have used click-It chemistry and LC-MS analysis and identified 431 target proteins of O-GlcNAc modification in retinal PC using an alkynyl-modified GlcNAc analog (GlcNAlk). 24788674 8 41 theme alkynyl-modified 1428:1443 arg1 GlcNAlk 1460:1466 GlcNAlk 1460:1466 GlcNAlk 1460:1466 To gain insight into the molecular mechanisms involved, we have used click-It chemistry and LC-MS analysis and identified 431 target proteins of O-GlcNAc modification in retinal PC using an alkynyl-modified GlcNAc analog (GlcNAlk). 24788674 3 42 theme retinal 473:479 arg1 PC 481:482 retinal PC 473:482 retinal PC 473:482 However, the mechanisms behind this selective sensitivity of retinal PC to hyperglycemia are undefined. 24788674 5 43 theme high 823:826 arg1 glucose 828:834 high glucose 823:834 high glucose 823:834 We have recently demonstrated that the level of O-GlcNAc modification in response to high glucose is variable in various retinal vascular cells. 24788674 0 44 dep targets 40:46 arg1 implication 76:86 implication 76:86 implication of p53 in pathogenesis of diabetic retinopathy 76:133 Identification of O-GlcNAc modification targets in mouse retinal pericytes: implication of p53 in pathogenesis of diabetic retinopathy. 24788674 4 45 theme O-linked 520:527 arg1 modification 562:573 The O-linked β-N-acetylglucosamine (O-GlcNAc) modification 516:573 The O-linked β-N-acetylglucosamine (O-GlcNAc) modification 516:573 The O-linked β-N-acetylglucosamine (O-GlcNAc) modification is elevated under hyperglycemic condition, and thus, may present an important molecular modification impacting the hyperglycemia-driven complications of diabetes. 24788674 11 46 theme increased 1742:1750 arg1 modification 1761:1772 increased O-GlcNAc modification 1742:1772 increased O-GlcNAc modification of p53 1742:1779 Our results indicated that increased O-GlcNAc modification of p53 was associated with an increase in its protein levels in retinal PC. 24788674 13 47 theme modification 2048:2059 arg1 modulation 2025:2034 modulation 2025:2034 modulation of O-GlcNAc modification 2025:2059 Thus, modulation of O-GlcNAc modification may provide a novel treatment strategy to prevent the initiation and progression of DR. 24788674 10 48 theme processes 1704:1712 arg1 aspects 1682:1688 various aspects 1674:1688 various aspects of cell death processes 1674:1712 We have identified at least 34 of these proteins with important roles in various aspects of cell death processes. 24788674 1 49 theme diabetic 224:231 arg1 DR 246:247 DR 246:247 DR 246:247 Hyperglycemia is the primary cause of the majority of diabetes complications, including diabetic retinopathy (DR). 24788674 1 49 theme diabetic 224:231 arg1 retinopathy 233:243 diabetic retinopathy 224:243 diabetic retinopathy (DR) 224:248 Hyperglycemia is the primary cause of the majority of diabetes complications, including diabetic retinopathy (DR). 24788674 10 50 theme various 1674:1680 arg1 aspects 1682:1688 various aspects 1674:1688 various aspects of cell death processes 1674:1712 We have identified at least 34 of these proteins with important roles in various aspects of cell death processes. 24788674 7 51 theme high 1141:1144 arg1 glucose 1146:1152 high glucose 1141:1152 high glucose 1141:1152 Here we show that these differences translated into functional changes, with an increase in apoptosis of retinal PC, not just under high glucose but also under treatment with O-GlcNAc modification inducers, PUGNAc and Thiamet-G. 24788674 2 52 theme retinal 349:355 arg1 loss 388:391 early loss 382:391 early loss of pericytes (PC) 382:409 Hyperglycemic conditions have a detrimental effect on many tissues and cell types, especially the retinal vascular cells including early loss of pericytes (PC). 24788674 2 52 theme retinal 349:355 arg1 cells 366:370 the retinal vascular cells 345:370 the retinal vascular cells 345:370 Hyperglycemic conditions have a detrimental effect on many tissues and cell types, especially the retinal vascular cells including early loss of pericytes (PC). 24788674 6 53 theme O-GlcNAc 933:940 arg1 modification 942:953 O-GlcNAc modification 933:953 O-GlcNAc modification 933:953 Retinal PC responded with the highest increase in O-GlcNAc modification compared to retinal endothelial cells and astrocytes. 24788674 11 54 mod modification 1761:1772 arg3 O-GlcNAc 1752:1759 increased O-GlcNAc modification 1742:1772 increased O-GlcNAc modification of p53 1742:1779 Our results indicated that increased O-GlcNAc modification of p53 was associated with an increase in its protein levels in retinal PC. 24788674 11 54 mod modification 1761:1772 arg1 p53 1777:1779 p53 1777:1779 p53 1777:1779 Our results indicated that increased O-GlcNAc modification of p53 was associated with an increase in its protein levels in retinal PC. 24788674 6 55 from increase 921:928 arg1 modification 942:953 O-GlcNAc modification 933:953 O-GlcNAc modification 933:953 Retinal PC responded with the highest increase in O-GlcNAc modification compared to retinal endothelial cells and astrocytes. 24788674 0 56 theme mouse 51:55 arg1 pericytes 65:73 mouse retinal pericytes 51:73 mouse retinal pericytes 51:73 Identification of O-GlcNAc modification targets in mouse retinal pericytes: implication of p53 in pathogenesis of diabetic retinopathy. 24788674 7 57 with treatment 1169:1177 arg1 Thiamet-G 1227:1235 Thiamet-G 1227:1235 Thiamet-G 1227:1235 Here we show that these differences translated into functional changes, with an increase in apoptosis of retinal PC, not just under high glucose but also under treatment with O-GlcNAc modification inducers, PUGNAc and Thiamet-G. 24788674 7 57 with treatment 1169:1177 arg1 PUGNAc 1216:1221 PUGNAc 1216:1221 PUGNAc 1216:1221 Here we show that these differences translated into functional changes, with an increase in apoptosis of retinal PC, not just under high glucose but also under treatment with O-GlcNAc modification inducers, PUGNAc and Thiamet-G. 24788674 7 57 with treatment 1169:1177 arg1 inducers 1206:1213 O-GlcNAc modification inducers 1184:1213 O-GlcNAc modification inducers 1184:1213 Here we show that these differences translated into functional changes, with an increase in apoptosis of retinal PC, not just under high glucose but also under treatment with O-GlcNAc modification inducers, PUGNAc and Thiamet-G. 24788674 4 58 theme important 643:651 arg1 modification 663:674 an important molecular modification 640:674 an important molecular modification impacting the hyperglycemia-driven complications of diabetes 640:735 The O-linked β-N-acetylglucosamine (O-GlcNAc) modification is elevated under hyperglycemic condition, and thus, may present an important molecular modification impacting the hyperglycemia-driven complications of diabetes. 24788674 7 59 theme retinal 1114:1120 arg1 PC 1122:1123 retinal PC 1114:1123 retinal PC 1114:1123 Here we show that these differences translated into functional changes, with an increase in apoptosis of retinal PC, not just under high glucose but also under treatment with O-GlcNAc modification inducers, PUGNAc and Thiamet-G. 24788674 1 60 theme majority 178:185 arg1 Hyperglycemia 136:148 Hyperglycemia 136:148 Hyperglycemia 136:148 Hyperglycemia is the primary cause of the majority of diabetes complications, including diabetic retinopathy (DR). 24788674 1 60 theme majority 178:185 arg1 cause 165:169 the primary cause 153:169 the primary cause of the majority of diabetes complications, including diabetic retinopathy (DR) 153:248 Hyperglycemia is the primary cause of the majority of diabetes complications, including diabetic retinopathy (DR). 24788674 8 61 theme molecular 1263:1271 arg1 mechanisms 1273:1282 the molecular mechanisms 1259:1282 the molecular mechanisms involved 1259:1291 To gain insight into the molecular mechanisms involved, we have used click-It chemistry and LC-MS analysis and identified 431 target proteins of O-GlcNAc modification in retinal PC using an alkynyl-modified GlcNAc analog (GlcNAlk). 24788674 11 62 theme protein 1820:1826 arg1 levels 1828:1833 its protein levels 1816:1833 its protein levels in retinal PC 1816:1847 Our results indicated that increased O-GlcNAc modification of p53 was associated with an increase in its protein levels in retinal PC. 24788674 0 63 theme retinopathy 123:133 arg1 pathogenesis 98:109 pathogenesis 98:109 pathogenesis of diabetic retinopathy 98:133 Identification of O-GlcNAc modification targets in mouse retinal pericytes: implication of p53 in pathogenesis of diabetic retinopathy. 24788674 2 64 theme many 305:308 arg1 loss 388:391 early loss 382:391 early loss of pericytes (PC) 382:409 Hyperglycemic conditions have a detrimental effect on many tissues and cell types, especially the retinal vascular cells including early loss of pericytes (PC). 24788674 2 64 theme many 305:308 arg1 tissues 310:316 many tissues 305:316 many tissues 305:316 Hyperglycemic conditions have a detrimental effect on many tissues and cell types, especially the retinal vascular cells including early loss of pericytes (PC). 24788674 9 65 theme O-GlcNAc 1480:1487 arg1 proteins 1496:1503 the O-GlcNAc target proteins 1476:1503 the O-GlcNAc target proteins identified here 1476:1519 Among the O-GlcNAc target proteins identified here 115 of them were not previously reported to be target of O-GlcNAc modification. 24788674 12 66 theme PC 1999:2000 arg1 loss 1991:1994 selective early loss 1975:1994 selective early loss of PC during diabetes 1975:2016 Together our results suggest that post-translational O-GlcNAc modification of p53 and its increased levels may contribute to selective early loss of PC during diabetes. 24788674 10 67 theme proteins 1641:1648 arg1 34 1629:1630 34 1629:1630 34 1629:1630 We have identified at least 34 of these proteins with important roles in various aspects of cell death processes. 24788674 10 67 theme proteins 1641:1648 arg1 proteins 1641:1648 these proteins 1635:1648 these proteins 1635:1648 We have identified at least 34 of these proteins with important roles in various aspects of cell death processes. 24788674 12 68 mod modification 1912:1923 arg1 p53 1928:1930 p53 1928:1930 p53 1928:1930 Together our results suggest that post-translational O-GlcNAc modification of p53 and its increased levels may contribute to selective early loss of PC during diabetes. 24788674 12 68 mod modification 1912:1923 arg3 O-GlcNAc 1903:1910 post-translational O-GlcNAc modification 1884:1923 post-translational O-GlcNAc modification of p53 and its increased levels 1884:1955 Together our results suggest that post-translational O-GlcNAc modification of p53 and its increased levels may contribute to selective early loss of PC during diabetes. 24788674 12 68 mod modification 1912:1923 arg1 levels 1950:1955 its increased levels 1936:1955 its increased levels 1936:1955 Together our results suggest that post-translational O-GlcNAc modification of p53 and its increased levels may contribute to selective early loss of PC during diabetes. 24788674 13 69 theme DR 2145:2146 arg1 progression 2130:2140 progression 2130:2140 progression 2130:2140 Thus, modulation of O-GlcNAc modification may provide a novel treatment strategy to prevent the initiation and progression of DR. 24788674 13 69 theme DR 2145:2146 arg1 initiation 2115:2124 initiation 2115:2124 initiation 2115:2124 Thus, modulation of O-GlcNAc modification may provide a novel treatment strategy to prevent the initiation and progression of DR. 24788674 5 70 theme vascular 867:874 arg1 cells 876:880 various retinal vascular cells 851:880 various retinal vascular cells 851:880 We have recently demonstrated that the level of O-GlcNAc modification in response to high glucose is variable in various retinal vascular cells. 24788674 8 71 used used 1302:1305 arg2 we 1294:1295 we 1294:1295 we 1294:1295 To gain insight into the molecular mechanisms involved, we have used click-It chemistry and LC-MS analysis and identified 431 target proteins of O-GlcNAc modification in retinal PC using an alkynyl-modified GlcNAc analog (GlcNAlk). 24788674 7 72 theme functional 1061:1070 arg1 changes 1072:1078 functional changes 1061:1078 functional changes 1061:1078 Here we show that these differences translated into functional changes, with an increase in apoptosis of retinal PC, not just under high glucose but also under treatment with O-GlcNAc modification inducers, PUGNAc and Thiamet-G. 24788674 12 73 theme selective 1975:1983 arg1 loss 1991:1994 selective early loss 1975:1994 selective early loss of PC during diabetes 1975:2016 Together our results suggest that post-translational O-GlcNAc modification of p53 and its increased levels may contribute to selective early loss of PC during diabetes. 24788674 6 74 theme retinal 967:973 arg1 cells 987:991 retinal endothelial cells 967:991 retinal endothelial cells 967:991 Retinal PC responded with the highest increase in O-GlcNAc modification compared to retinal endothelial cells and astrocytes. 24788674 4 75 theme diabetes 728:735 arg1 complications 711:723 the hyperglycemia-driven complications 686:723 the hyperglycemia-driven complications of diabetes 686:735 The O-linked β-N-acetylglucosamine (O-GlcNAc) modification is elevated under hyperglycemic condition, and thus, may present an important molecular modification impacting the hyperglycemia-driven complications of diabetes. 24788674 11 76 theme p53 1777:1779 arg1 modification 1761:1772 increased O-GlcNAc modification 1742:1772 increased O-GlcNAc modification of p53 1742:1779 Our results indicated that increased O-GlcNAc modification of p53 was associated with an increase in its protein levels in retinal PC. 24788674 1 77 theme diabetes 190:197 arg1 complications 199:211 diabetes complications 190:211 diabetes complications 190:211 Hyperglycemia is the primary cause of the majority of diabetes complications, including diabetic retinopathy (DR). 24788674 1 77 theme diabetes 190:197 arg1 retinopathy 233:243 diabetic retinopathy 224:243 diabetic retinopathy (DR) 224:248 Hyperglycemia is the primary cause of the majority of diabetes complications, including diabetic retinopathy (DR). 24788674 8 78 theme LC-MS 1330:1334 arg1 analysis 1336:1343 LC-MS analysis 1330:1343 LC-MS analysis 1330:1343 To gain insight into the molecular mechanisms involved, we have used click-It chemistry and LC-MS analysis and identified 431 target proteins of O-GlcNAc modification in retinal PC using an alkynyl-modified GlcNAc analog (GlcNAlk). 24788674 5 79 theme O-GlcNAc 786:793 arg1 modification 795:806 O-GlcNAc modification 786:806 O-GlcNAc modification 786:806 We have recently demonstrated that the level of O-GlcNAc modification in response to high glucose is variable in various retinal vascular cells. 24788674 12 80 theme increased 1940:1948 arg1 levels 1950:1955 its increased levels 1936:1955 its increased levels 1936:1955 Together our results suggest that post-translational O-GlcNAc modification of p53 and its increased levels may contribute to selective early loss of PC during diabetes. 24788674 1 81 theme primary 157:163 arg1 Hyperglycemia 136:148 Hyperglycemia 136:148 Hyperglycemia 136:148 Hyperglycemia is the primary cause of the majority of diabetes complications, including diabetic retinopathy (DR). 24788674 1 81 theme primary 157:163 arg1 cause 165:169 the primary cause 153:169 the primary cause of the majority of diabetes complications, including diabetic retinopathy (DR) 153:248 Hyperglycemia is the primary cause of the majority of diabetes complications, including diabetic retinopathy (DR). 24788674 2 82 theme cell 322:325 arg1 loss 388:391 early loss 382:391 early loss of pericytes (PC) 382:409 Hyperglycemic conditions have a detrimental effect on many tissues and cell types, especially the retinal vascular cells including early loss of pericytes (PC). 24788674 2 82 theme cell 322:325 arg1 types 327:331 cell types 322:331 cell types 322:331 Hyperglycemic conditions have a detrimental effect on many tissues and cell types, especially the retinal vascular cells including early loss of pericytes (PC). 24788674 1 83 theme complications 199:211 arg1 majority 178:185 the majority 174:185 the majority of diabetes complications, including diabetic retinopathy (DR) 174:248 Hyperglycemia is the primary cause of the majority of diabetes complications, including diabetic retinopathy (DR). 24788674 7 84 theme modification 1193:1204 arg1 Thiamet-G 1227:1235 Thiamet-G 1227:1235 Thiamet-G 1227:1235 Here we show that these differences translated into functional changes, with an increase in apoptosis of retinal PC, not just under high glucose but also under treatment with O-GlcNAc modification inducers, PUGNAc and Thiamet-G. 24788674 7 84 theme modification 1193:1204 arg1 PUGNAc 1216:1221 PUGNAc 1216:1221 PUGNAc 1216:1221 Here we show that these differences translated into functional changes, with an increase in apoptosis of retinal PC, not just under high glucose but also under treatment with O-GlcNAc modification inducers, PUGNAc and Thiamet-G. 24788674 7 84 theme modification 1193:1204 arg1 inducers 1206:1213 O-GlcNAc modification inducers 1184:1213 O-GlcNAc modification inducers 1184:1213 Here we show that these differences translated into functional changes, with an increase in apoptosis of retinal PC, not just under high glucose but also under treatment with O-GlcNAc modification inducers, PUGNAc and Thiamet-G. 24788674 13 85 theme novel 2075:2079 arg1 strategy 2091:2098 a novel treatment strategy 2073:2098 a novel treatment strategy to prevent the initiation and progression of DR 2073:2146 Thus, modulation of O-GlcNAc modification may provide a novel treatment strategy to prevent the initiation and progression of DR. 24788674 9 86 theme O-GlcNAc 1578:1585 arg1 modification 1587:1598 O-GlcNAc modification 1578:1598 O-GlcNAc modification 1578:1598 Among the O-GlcNAc target proteins identified here 115 of them were not previously reported to be target of O-GlcNAc modification. 24788674 4 87 theme O-GlcNAc 552:559 arg1 modification 562:573 The O-linked β-N-acetylglucosamine (O-GlcNAc) modification 516:573 The O-linked β-N-acetylglucosamine (O-GlcNAc) modification 516:573 The O-linked β-N-acetylglucosamine (O-GlcNAc) modification is elevated under hyperglycemic condition, and thus, may present an important molecular modification impacting the hyperglycemia-driven complications of diabetes. 24788674 8 88 theme O-GlcNAc 1383:1390 arg1 modification 1392:1403 O-GlcNAc modification 1383:1403 O-GlcNAc modification 1383:1403 To gain insight into the molecular mechanisms involved, we have used click-It chemistry and LC-MS analysis and identified 431 target proteins of O-GlcNAc modification in retinal PC using an alkynyl-modified GlcNAc analog (GlcNAlk). 24788674 0 89 theme modification 27:38 arg1 Identification 0:13 Identification 0:13 Identification of O-GlcNAc modification 0:38 Identification of O-GlcNAc modification targets in mouse retinal pericytes: implication of p53 in pathogenesis of diabetic retinopathy. 24788674 3 90 theme selective 448:456 arg1 sensitivity 458:468 this selective sensitivity 443:468 this selective sensitivity of retinal PC to hyperglycemia 443:499 However, the mechanisms behind this selective sensitivity of retinal PC to hyperglycemia are undefined. 24788674 12 91 theme O-GlcNAc 1903:1910 arg1 modification 1912:1923 post-translational O-GlcNAc modification 1884:1923 post-translational O-GlcNAc modification of p53 and its increased levels 1884:1955 Together our results suggest that post-translational O-GlcNAc modification of p53 and its increased levels may contribute to selective early loss of PC during diabetes. 24788674 2 92 theme pericytes 396:404 arg1 loss 388:391 early loss 382:391 early loss of pericytes (PC) 382:409 Hyperglycemic conditions have a detrimental effect on many tissues and cell types, especially the retinal vascular cells including early loss of pericytes (PC). 24788674 0 93 theme retinal 57:63 arg1 pericytes 65:73 mouse retinal pericytes 51:73 mouse retinal pericytes 51:73 Identification of O-GlcNAc modification targets in mouse retinal pericytes: implication of p53 in pathogenesis of diabetic retinopathy. 24788674 4 94 theme β-N-acetylglucosamine 529:549 arg1 modification 562:573 The O-linked β-N-acetylglucosamine (O-GlcNAc) modification 516:573 The O-linked β-N-acetylglucosamine (O-GlcNAc) modification 516:573 The O-linked β-N-acetylglucosamine (O-GlcNAc) modification is elevated under hyperglycemic condition, and thus, may present an important molecular modification impacting the hyperglycemia-driven complications of diabetes. 24788674 13 95 theme O-GlcNAc 2039:2046 arg1 modification 2048:2059 O-GlcNAc modification 2039:2059 O-GlcNAc modification 2039:2059 Thus, modulation of O-GlcNAc modification may provide a novel treatment strategy to prevent the initiation and progression of DR. 24788674 3 96 theme PC 481:482 arg1 sensitivity 458:468 this selective sensitivity 443:468 this selective sensitivity of retinal PC to hyperglycemia 443:499 However, the mechanisms behind this selective sensitivity of retinal PC to hyperglycemia are undefined. 24788674 10 97 from roles 1665:1669 arg1 aspects 1682:1688 various aspects 1674:1688 various aspects of cell death processes 1674:1712 We have identified at least 34 of these proteins with important roles in various aspects of cell death processes. 24788674 8 98 theme GlcNAc 1445:1450 arg1 analog 1452:1457 an alkynyl-modified GlcNAc analog 1425:1457 an alkynyl-modified GlcNAc analog (GlcNAlk) 1425:1467 To gain insight into the molecular mechanisms involved, we have used click-It chemistry and LC-MS analysis and identified 431 target proteins of O-GlcNAc modification in retinal PC using an alkynyl-modified GlcNAc analog (GlcNAlk). 24788674 8 98 theme GlcNAc 1445:1450 arg1 GlcNAlk 1460:1466 GlcNAlk 1460:1466 GlcNAlk 1460:1466 To gain insight into the molecular mechanisms involved, we have used click-It chemistry and LC-MS analysis and identified 431 target proteins of O-GlcNAc modification in retinal PC using an alkynyl-modified GlcNAc analog (GlcNAlk). 24788674 10 99 theme death 1698:1702 arg1 processes 1704:1712 cell death processes 1693:1712 cell death processes 1693:1712 We have identified at least 34 of these proteins with important roles in various aspects of cell death processes. 24788674 2 100 theme vascular 357:364 arg1 loss 388:391 early loss 382:391 early loss of pericytes (PC) 382:409 Hyperglycemic conditions have a detrimental effect on many tissues and cell types, especially the retinal vascular cells including early loss of pericytes (PC). 24788674 2 100 theme vascular 357:364 arg1 cells 366:370 the retinal vascular cells 345:370 the retinal vascular cells 345:370 Hyperglycemic conditions have a detrimental effect on many tissues and cell types, especially the retinal vascular cells including early loss of pericytes (PC). 26407992 12 0 theme dissociation 2027:2038 arg1 conditions 2040:2049 variable higher-energy collisional dissociation conditions 1992:2049 variable higher-energy collisional dissociation conditions 1992:2049 The fragmentation behavior of CS glycopeptides under variable higher-energy collisional dissociation conditions displays an energy dependence that may be used to obtain complementary structural details. 26407992 6 1 theme chain 1049:1053 arg1 linkage 1055:1061 heavy chain linkage and cross-linkage region 1043:1086 linkage 1055:1061 In this study we employed a glycoproteomics protocol to enrich and analyze light and heavy chain linkage and cross-linkage region CS glycopeptides derived from the IαI complex of human plasma, urine and cerebrospinal fluid samples. 26407992 2 2 theme inter-α-trypsin 372:386 arg1 complex 398:404 The inter-α-trypsin inhibitor complex 368:404 The inter-α-trypsin inhibitor complex 368:404 The inter-α-trypsin inhibitor complex is abundant in plasma and associated with inflammation, kidney diseases, cancer and diabetes. 26407992 12 3 theme CS 1969:1970 arg1 glycopeptides 1972:1984 CS glycopeptides 1969:1984 CS glycopeptides 1969:1984 The fragmentation behavior of CS glycopeptides under variable higher-energy collisional dissociation conditions displays an energy dependence that may be used to obtain complementary structural details. 26407992 6 4 theme plasma 1143:1148 arg1 samples 1181:1187 human plasma, urine and cerebrospinal fluid samples 1137:1187 human plasma, urine and cerebrospinal fluid samples 1137:1187 In this study we employed a glycoproteomics protocol to enrich and analyze light and heavy chain linkage and cross-linkage region CS glycopeptides derived from the IαI complex of human plasma, urine and cerebrospinal fluid samples. 26407992 4 5 theme innermost 618:626 arg1 monosaccharides 633:647 The innermost four monosaccharides 614:647 The innermost four monosaccharides (GlcAβ3Galβ3Galβ4Xylβ-O-) 614:673 The innermost four monosaccharides (GlcAβ3Galβ3Galβ4Xylβ-O-) compose the linkage region, believed to be uniform with a 4-O-sulfation to the outer Gal. 26407992 4 5 theme innermost 618:626 arg1 GlcAβ3Galβ3Galβ4Xylβ-O- 650:672 GlcAβ3Galβ3Galβ4Xylβ-O- 650:672 GlcAβ3Galβ3Galβ4Xylβ-O- 650:672 The innermost four monosaccharides (GlcAβ3Galβ3Galβ4Xylβ-O-) compose the linkage region, believed to be uniform with a 4-O-sulfation to the outer Gal. 26407992 3 6 theme 23-55 567:571 arg1 monosaccharides 573:587 23-55 monosaccharides 567:587 23-55 monosaccharides with 4-9 sulfate groups 567:611 Bikunin is modified at Ser-10 by a single low-sulfated CS chain of 23-55 monosaccharides with 4-9 sulfate groups. 26407992 4 7 with uniform 718:724 arg1 4-O-sulfation 733:745 a 4-O-sulfation 731:745 a 4-O-sulfation to the outer Gal 731:762 The innermost four monosaccharides (GlcAβ3Galβ3Galβ4Xylβ-O-) compose the linkage region, believed to be uniform with a 4-O-sulfation to the outer Gal. 26407992 13 8 theme sodium 2180:2185 arg1 adducts 2187:2193 sodium adducts 2180:2193 sodium adducts 2180:2193 Finally, we show that the analysis of sodium adducts provides confirmatory information about the positions of glycan substituents. 26407992 12 9 theme collisional 2015:2025 arg1 conditions 2040:2049 variable higher-energy collisional dissociation conditions 1992:2049 variable higher-energy collisional dissociation conditions 1992:2049 The fragmentation behavior of CS glycopeptides under variable higher-energy collisional dissociation conditions displays an energy dependence that may be used to obtain complementary structural details. 26407992 6 10 theme IαI 1122:1124 arg1 complex 1126:1132 the IαI complex 1118:1132 the IαI complex of human plasma, urine and cerebrospinal fluid samples 1118:1187 In this study we employed a glycoproteomics protocol to enrich and analyze light and heavy chain linkage and cross-linkage region CS glycopeptides derived from the IαI complex of human plasma, urine and cerebrospinal fluid samples. 26407992 10 11 link O-linked 1730:1737 arg1 glycans 1739:1745 mono- and disialylated core 1 O-linked glycans 1700:1745 mono- and disialylated core 1 O-linked glycans 1700:1745 We also identified novel Neu5Ac and Fuc modifications of the linkage region as well as the presence of mono- and disialylated core 1 O-linked glycans on Thr-17. 26407992 3 12 theme sulfate 598:604 arg1 groups 606:611 4-9 sulfate groups 594:611 4-9 sulfate groups 594:611 Bikunin is modified at Ser-10 by a single low-sulfated CS chain of 23-55 monosaccharides with 4-9 sulfate groups. 26407992 11 13 dep residues 1929:1936 arg1 either 1887:1892 either 1887:1892 either 1887:1892 Heavy chains H1 and H2 were identified cross-linked to GalNAc residues one or two GlcA residues apart and H1 was found linked to either the terminal or subterminal GalNAc residues. 26407992 7 14 theme higher-energy 1349:1361 arg1 dissociation 1375:1386 higher-energy collisional dissociation 1349:1386 higher-energy collisional dissociation 1349:1386 The samples were trypsinized, enriched by strong anion exchange chromatography, partially depolymerized with chondroitinase ABC and analyzed by LC-MS/MS using higher-energy collisional dissociation. 26407992 12 15 used used 2093:2096 arg2 dependence 2070:2079 an energy dependence 2060:2079 an energy dependence that may be used to obtain complementary structural details 2060:2139 The fragmentation behavior of CS glycopeptides under variable higher-energy collisional dissociation conditions displays an energy dependence that may be used to obtain complementary structural details. 26407992 10 16 theme mono- 1700:1704 arg1 glycans 1739:1745 mono- and disialylated core 1 O-linked glycans 1700:1745 mono- and disialylated core 1 O-linked glycans 1700:1745 We also identified novel Neu5Ac and Fuc modifications of the linkage region as well as the presence of mono- and disialylated core 1 O-linked glycans on Thr-17. 26407992 7 17 theme collisional 1363:1373 arg1 dissociation 1375:1386 higher-energy collisional dissociation 1349:1386 higher-energy collisional dissociation 1349:1386 The samples were trypsinized, enriched by strong anion exchange chromatography, partially depolymerized with chondroitinase ABC and analyzed by LC-MS/MS using higher-energy collisional dissociation. 26407992 4 18 theme linkage 687:693 arg1 region 695:700 the linkage region 683:700 the linkage region 683:700 The innermost four monosaccharides (GlcAβ3Galβ3Galβ4Xylβ-O-) compose the linkage region, believed to be uniform with a 4-O-sulfation to the outer Gal. 26407992 0 19 theme Inter-α-Trypsin 127:141 arg1 Complex 153:159 The Human Inter-α-Trypsin Inhibitor Complex 117:159 The Human Inter-α-Trypsin Inhibitor Complex 117:159 Positive Mode LC-MS/MS Analysis of Chondroitin Sulfate Modified Glycopeptides Derived from Light and Heavy Chains of The Human Inter-α-Trypsin Inhibitor Complex. 26407992 5 20 theme GalNAcβ4GlcAβ3 862:875 arg1 end 856:858 the nonsulfated nonreducing end 828:858 the nonsulfated nonreducing end 828:858 The cross-linkage region of the bikunin CS chain is located in the nonsulfated nonreducing end, (GalNAcβ4GlcAβ3)(n), to which heavy chains (H1-H3) may be bound in GalNAc to Asp ester linkages. 26407992 5 20 theme GalNAcβ4GlcAβ3 862:875 arg1 n 878:878 (GalNAcβ4GlcAβ3)(n) 861:879 (GalNAcβ4GlcAβ3)(n) 861:879 The cross-linkage region of the bikunin CS chain is located in the nonsulfated nonreducing end, (GalNAcβ4GlcAβ3)(n), to which heavy chains (H1-H3) may be bound in GalNAc to Asp ester linkages. 26407992 8 21 theme bikunin 1445:1451 arg1 heterogeneous 1463:1475 heterogeneous 1463:1475 heterogeneous 1463:1475 The analyses demonstrated that the CS linkage region of bikunin is highly heterogeneous. 26407992 8 21 theme bikunin 1445:1451 arg1 region 1435:1440 the CS linkage region 1420:1440 the CS linkage region of bikunin 1420:1451 The analyses demonstrated that the CS linkage region of bikunin is highly heterogeneous. 26407992 6 22 theme samples 1181:1187 arg1 complex 1126:1132 the IαI complex 1118:1132 the IαI complex of human plasma, urine and cerebrospinal fluid samples 1118:1187 In this study we employed a glycoproteomics protocol to enrich and analyze light and heavy chain linkage and cross-linkage region CS glycopeptides derived from the IαI complex of human plasma, urine and cerebrospinal fluid samples. 26407992 0 23 theme Complex 153:159 arg1 Light 91:95 Light 91:95 Light 91:95 Positive Mode LC-MS/MS Analysis of Chondroitin Sulfate Modified Glycopeptides Derived from Light and Heavy Chains of The Human Inter-α-Trypsin Inhibitor Complex. 26407992 0 23 theme Complex 153:159 arg1 Chains 107:112 Heavy Chains 101:112 Heavy Chains 101:112 Positive Mode LC-MS/MS Analysis of Chondroitin Sulfate Modified Glycopeptides Derived from Light and Heavy Chains of The Human Inter-α-Trypsin Inhibitor Complex. 26407992 11 24 theme subterminal 1910:1920 arg1 residues 1929:1936 either the terminal or subterminal GalNAc residues 1887:1936 residues 1929:1936 Heavy chains H1 and H2 were identified cross-linked to GalNAc residues one or two GlcA residues apart and H1 was found linked to either the terminal or subterminal GalNAc residues. 26407992 5 25 from end 856:858 arg1 located 817:823 located 817:823 located 817:823 The cross-linkage region of the bikunin CS chain is located in the nonsulfated nonreducing end, (GalNAcβ4GlcAβ3)(n), to which heavy chains (H1-H3) may be bound in GalNAc to Asp ester linkages. 26407992 5 25 from end 856:858 arg1 region 783:788 The cross-linkage region 765:788 The cross-linkage region of the bikunin CS chain 765:812 The cross-linkage region of the bikunin CS chain is located in the nonsulfated nonreducing end, (GalNAcβ4GlcAβ3)(n), to which heavy chains (H1-H3) may be bound in GalNAc to Asp ester linkages. 26407992 6 26 theme cerebrospinal 1161:1173 arg1 fluid 1175:1179 cerebrospinal fluid 1161:1179 cerebrospinal fluid 1161:1179 In this study we employed a glycoproteomics protocol to enrich and analyze light and heavy chain linkage and cross-linkage region CS glycopeptides derived from the IαI complex of human plasma, urine and cerebrospinal fluid samples. 26407992 4 27 theme outer 754:758 arg1 Gal 760:762 the outer Gal 750:762 the outer Gal 750:762 The innermost four monosaccharides (GlcAβ3Galβ3Galβ4Xylβ-O-) compose the linkage region, believed to be uniform with a 4-O-sulfation to the outer Gal. 26407992 6 28 theme urine 1151:1155 arg1 samples 1181:1187 human plasma, urine and cerebrospinal fluid samples 1137:1187 human plasma, urine and cerebrospinal fluid samples 1137:1187 In this study we employed a glycoproteomics protocol to enrich and analyze light and heavy chain linkage and cross-linkage region CS glycopeptides derived from the IαI complex of human plasma, urine and cerebrospinal fluid samples. 26407992 6 29 attach derived 1105:1111 arg2 glycopeptides 1091:1103 light and heavy chain linkage and cross-linkage region CS glycopeptides 1033:1103 light and heavy chain linkage and cross-linkage region CS glycopeptides derived from the IαI complex of human plasma, urine and cerebrospinal fluid samples 1033:1187 In this study we employed a glycoproteomics protocol to enrich and analyze light and heavy chain linkage and cross-linkage region CS glycopeptides derived from the IαI complex of human plasma, urine and cerebrospinal fluid samples. 26407992 6 29 attach derived 1105:1111 arg1 complex 1126:1132 the IαI complex 1118:1132 the IαI complex of human plasma, urine and cerebrospinal fluid samples 1118:1187 In this study we employed a glycoproteomics protocol to enrich and analyze light and heavy chain linkage and cross-linkage region CS glycopeptides derived from the IαI complex of human plasma, urine and cerebrospinal fluid samples. 26407992 10 30 gly disialylated 1710:1721 arg1 glycans 1739:1745 mono- and disialylated core 1 O-linked glycans 1700:1745 mono- and disialylated core 1 O-linked glycans 1700:1745 We also identified novel Neu5Ac and Fuc modifications of the linkage region as well as the presence of mono- and disialylated core 1 O-linked glycans on Thr-17. 26407992 5 31 theme nonreducing 844:854 arg1 end 856:858 the nonsulfated nonreducing end 828:858 the nonsulfated nonreducing end 828:858 The cross-linkage region of the bikunin CS chain is located in the nonsulfated nonreducing end, (GalNAcβ4GlcAβ3)(n), to which heavy chains (H1-H3) may be bound in GalNAc to Asp ester linkages. 26407992 5 31 theme nonreducing 844:854 arg1 n 878:878 (GalNAcβ4GlcAβ3)(n) 861:879 (GalNAcβ4GlcAβ3)(n) 861:879 The cross-linkage region of the bikunin CS chain is located in the nonsulfated nonreducing end, (GalNAcβ4GlcAβ3)(n), to which heavy chains (H1-H3) may be bound in GalNAc to Asp ester linkages. 26407992 9 32 theme Gal 1510:1512 arg1 residue 1514:1520 the Gal residue 1506:1520 the Gal residue 1506:1520 In addition to sulfation of the Gal residue, Xyl phosphorylation was observed although exclusively in urinary samples. 26407992 9 33 located observed 1547:1554 arg1 samples 1588:1594 urinary samples 1580:1594 urinary samples 1580:1594 In addition to sulfation of the Gal residue, Xyl phosphorylation was observed although exclusively in urinary samples. 26407992 9 33 located observed 1547:1554 arg2 phosphorylation 1527:1541 Xyl phosphorylation 1523:1541 Xyl phosphorylation 1523:1541 In addition to sulfation of the Gal residue, Xyl phosphorylation was observed although exclusively in urinary samples. 26407992 12 34 theme energy 2063:2068 arg1 dependence 2070:2079 an energy dependence 2060:2079 an energy dependence that may be used to obtain complementary structural details 2060:2139 The fragmentation behavior of CS glycopeptides under variable higher-energy collisional dissociation conditions displays an energy dependence that may be used to obtain complementary structural details. 26407992 11 35 theme Heavy 1758:1762 arg1 H2 1778:1779 H2 1778:1779 H2 1778:1779 Heavy chains H1 and H2 were identified cross-linked to GalNAc residues one or two GlcA residues apart and H1 was found linked to either the terminal or subterminal GalNAc residues. 26407992 11 35 theme Heavy 1758:1762 arg1 H1 1771:1772 H1 1771:1772 H1 1771:1772 Heavy chains H1 and H2 were identified cross-linked to GalNAc residues one or two GlcA residues apart and H1 was found linked to either the terminal or subterminal GalNAc residues. 26407992 11 35 theme Heavy 1758:1762 arg1 chains 1764:1769 Heavy chains H1 and H2 1758:1779 Heavy chains H1 and H2 1758:1779 Heavy chains H1 and H2 were identified cross-linked to GalNAc residues one or two GlcA residues apart and H1 was found linked to either the terminal or subterminal GalNAc residues. 26407992 5 36 theme bikunin 797:803 arg1 chain 808:812 the bikunin CS chain 793:812 the bikunin CS chain 793:812 The cross-linkage region of the bikunin CS chain is located in the nonsulfated nonreducing end, (GalNAcβ4GlcAβ3)(n), to which heavy chains (H1-H3) may be bound in GalNAc to Asp ester linkages. 26407992 1 37 theme inter-α-trypsin 166:180 arg1 arrangement 220:230 a macromolecular arrangement 203:230 a macromolecular arrangement of structurally related heavy chain proteins covalently cross-linked to the chondroitin sulfate (CS) chain of the proteoglycan bikunin 203:365 The inter-α-trypsin inhibitor complex is a macromolecular arrangement of structurally related heavy chain proteins covalently cross-linked to the chondroitin sulfate (CS) chain of the proteoglycan bikunin. 26407992 1 37 theme inter-α-trypsin 166:180 arg1 complex 192:198 The inter-α-trypsin inhibitor complex 162:198 The inter-α-trypsin inhibitor complex 162:198 The inter-α-trypsin inhibitor complex is a macromolecular arrangement of structurally related heavy chain proteins covalently cross-linked to the chondroitin sulfate (CS) chain of the proteoglycan bikunin. 26407992 9 38 dep sulfation 1493:1501 arg1 addition 1481:1488 addition 1481:1488 addition 1481:1488 In addition to sulfation of the Gal residue, Xyl phosphorylation was observed although exclusively in urinary samples. 26407992 10 39 theme glycans 1739:1745 arg1 presence 1688:1695 the presence 1684:1695 novel Neu5Ac and Fuc modifications of the linkage region as well as the presence of mono- and disialylated core 1 O-linked glycans 1616:1745 We also identified novel Neu5Ac and Fuc modifications of the linkage region as well as the presence of mono- and disialylated core 1 O-linked glycans on Thr-17. 26407992 10 39 theme glycans 1739:1745 arg1 Neu5Ac 1622:1627 novel Neu5Ac and Fuc modifications 1616:1649 Neu5Ac 1622:1627 We also identified novel Neu5Ac and Fuc modifications of the linkage region as well as the presence of mono- and disialylated core 1 O-linked glycans on Thr-17. 26407992 10 39 theme glycans 1739:1745 arg1 modifications 1637:1649 novel Neu5Ac and Fuc modifications 1616:1649 modifications 1637:1649 We also identified novel Neu5Ac and Fuc modifications of the linkage region as well as the presence of mono- and disialylated core 1 O-linked glycans on Thr-17. 26407992 11 40 theme terminal 1898:1905 arg1 residues 1929:1936 either the terminal or subterminal GalNAc residues 1887:1936 residues 1929:1936 Heavy chains H1 and H2 were identified cross-linked to GalNAc residues one or two GlcA residues apart and H1 was found linked to either the terminal or subterminal GalNAc residues. 26407992 5 41 theme cross-linkage 769:781 arg1 located 817:823 located 817:823 located 817:823 The cross-linkage region of the bikunin CS chain is located in the nonsulfated nonreducing end, (GalNAcβ4GlcAβ3)(n), to which heavy chains (H1-H3) may be bound in GalNAc to Asp ester linkages. 26407992 5 41 theme cross-linkage 769:781 arg1 region 783:788 The cross-linkage region 765:788 The cross-linkage region of the bikunin CS chain 765:812 The cross-linkage region of the bikunin CS chain is located in the nonsulfated nonreducing end, (GalNAcβ4GlcAβ3)(n), to which heavy chains (H1-H3) may be bound in GalNAc to Asp ester linkages. 26407992 0 42 theme Chondroitin 35:45 arg1 Sulfate 47:53 Chondroitin Sulfate 35:53 Chondroitin Sulfate 35:53 Positive Mode LC-MS/MS Analysis of Chondroitin Sulfate Modified Glycopeptides Derived from Light and Heavy Chains of The Human Inter-α-Trypsin Inhibitor Complex. 26407992 5 43 theme ester 942:946 arg1 linkages 948:955 Asp ester linkages 938:955 Asp ester linkages 938:955 The cross-linkage region of the bikunin CS chain is located in the nonsulfated nonreducing end, (GalNAcβ4GlcAβ3)(n), to which heavy chains (H1-H3) may be bound in GalNAc to Asp ester linkages. 26407992 6 44 theme light 1033:1037 arg1 glycopeptides 1091:1103 light and heavy chain linkage and cross-linkage region CS glycopeptides 1033:1103 light and heavy chain linkage and cross-linkage region CS glycopeptides derived from the IαI complex of human plasma, urine and cerebrospinal fluid samples 1033:1187 In this study we employed a glycoproteomics protocol to enrich and analyze light and heavy chain linkage and cross-linkage region CS glycopeptides derived from the IαI complex of human plasma, urine and cerebrospinal fluid samples. 26407992 0 45 theme Positive 0:7 arg1 Analysis 23:30 Positive Mode LC-MS/MS Analysis 0:30 Positive Mode LC-MS/MS Analysis of Chondroitin Sulfate 0:53 Positive Mode LC-MS/MS Analysis of Chondroitin Sulfate Modified Glycopeptides Derived from Light and Heavy Chains of The Human Inter-α-Trypsin Inhibitor Complex. 26407992 1 46 theme chondroitin 308:318 arg1 CS 329:330 CS 329:330 CS 329:330 The inter-α-trypsin inhibitor complex is a macromolecular arrangement of structurally related heavy chain proteins covalently cross-linked to the chondroitin sulfate (CS) chain of the proteoglycan bikunin. 26407992 1 46 theme chondroitin 308:318 arg1 sulfate 320:326 chondroitin sulfate 308:326 the chondroitin sulfate (CS) chain of the proteoglycan bikunin 304:365 The inter-α-trypsin inhibitor complex is a macromolecular arrangement of structurally related heavy chain proteins covalently cross-linked to the chondroitin sulfate (CS) chain of the proteoglycan bikunin. 26407992 5 47 located located 817:823 arg2 located 817:823 located 817:823 located 817:823 The cross-linkage region of the bikunin CS chain is located in the nonsulfated nonreducing end, (GalNAcβ4GlcAβ3)(n), to which heavy chains (H1-H3) may be bound in GalNAc to Asp ester linkages. 26407992 5 47 located located 817:823 arg1 end 856:858 the nonsulfated nonreducing end 828:858 the nonsulfated nonreducing end 828:858 The cross-linkage region of the bikunin CS chain is located in the nonsulfated nonreducing end, (GalNAcβ4GlcAβ3)(n), to which heavy chains (H1-H3) may be bound in GalNAc to Asp ester linkages. 26407992 5 47 located located 817:823 arg1 n 878:878 (GalNAcβ4GlcAβ3)(n) 861:879 (GalNAcβ4GlcAβ3)(n) 861:879 The cross-linkage region of the bikunin CS chain is located in the nonsulfated nonreducing end, (GalNAcβ4GlcAβ3)(n), to which heavy chains (H1-H3) may be bound in GalNAc to Asp ester linkages. 26407992 5 47 located located 817:823 arg2 region 783:788 The cross-linkage region 765:788 The cross-linkage region of the bikunin CS chain 765:812 The cross-linkage region of the bikunin CS chain is located in the nonsulfated nonreducing end, (GalNAcβ4GlcAβ3)(n), to which heavy chains (H1-H3) may be bound in GalNAc to Asp ester linkages. 26407992 0 48 theme LC-MS/MS 14:21 arg1 Analysis 23:30 Positive Mode LC-MS/MS Analysis 0:30 Positive Mode LC-MS/MS Analysis of Chondroitin Sulfate 0:53 Positive Mode LC-MS/MS Analysis of Chondroitin Sulfate Modified Glycopeptides Derived from Light and Heavy Chains of The Human Inter-α-Trypsin Inhibitor Complex. 26407992 10 49 theme O-linked 1730:1737 arg1 glycans 1739:1745 mono- and disialylated core 1 O-linked glycans 1700:1745 mono- and disialylated core 1 O-linked glycans 1700:1745 We also identified novel Neu5Ac and Fuc modifications of the linkage region as well as the presence of mono- and disialylated core 1 O-linked glycans on Thr-17. 26407992 9 50 theme urinary 1580:1586 arg1 samples 1588:1594 urinary samples 1580:1594 urinary samples 1580:1594 In addition to sulfation of the Gal residue, Xyl phosphorylation was observed although exclusively in urinary samples. 26407992 10 51 theme region 1666:1671 arg1 presence 1688:1695 the presence 1684:1695 novel Neu5Ac and Fuc modifications of the linkage region as well as the presence of mono- and disialylated core 1 O-linked glycans 1616:1745 We also identified novel Neu5Ac and Fuc modifications of the linkage region as well as the presence of mono- and disialylated core 1 O-linked glycans on Thr-17. 26407992 10 51 theme region 1666:1671 arg1 Neu5Ac 1622:1627 novel Neu5Ac and Fuc modifications 1616:1649 Neu5Ac 1622:1627 We also identified novel Neu5Ac and Fuc modifications of the linkage region as well as the presence of mono- and disialylated core 1 O-linked glycans on Thr-17. 26407992 10 51 theme region 1666:1671 arg1 modifications 1637:1649 novel Neu5Ac and Fuc modifications 1616:1649 modifications 1637:1649 We also identified novel Neu5Ac and Fuc modifications of the linkage region as well as the presence of mono- and disialylated core 1 O-linked glycans on Thr-17. 26407992 5 52 theme chain 808:812 arg1 located 817:823 located 817:823 located 817:823 The cross-linkage region of the bikunin CS chain is located in the nonsulfated nonreducing end, (GalNAcβ4GlcAβ3)(n), to which heavy chains (H1-H3) may be bound in GalNAc to Asp ester linkages. 26407992 5 52 theme chain 808:812 arg1 region 783:788 The cross-linkage region 765:788 The cross-linkage region of the bikunin CS chain 765:812 The cross-linkage region of the bikunin CS chain is located in the nonsulfated nonreducing end, (GalNAcβ4GlcAβ3)(n), to which heavy chains (H1-H3) may be bound in GalNAc to Asp ester linkages. 26407992 13 53 theme adducts 2187:2193 arg1 analysis 2168:2175 the analysis 2164:2175 the analysis of sodium adducts 2164:2193 Finally, we show that the analysis of sodium adducts provides confirmatory information about the positions of glycan substituents. 26407992 6 54 theme glycoproteomics 986:1000 arg1 protocol 1002:1009 a glycoproteomics protocol 984:1009 a glycoproteomics protocol 984:1009 In this study we employed a glycoproteomics protocol to enrich and analyze light and heavy chain linkage and cross-linkage region CS glycopeptides derived from the IαI complex of human plasma, urine and cerebrospinal fluid samples. 26407992 0 55 theme Sulfate 47:53 arg1 Analysis 23:30 Positive Mode LC-MS/MS Analysis 0:30 Positive Mode LC-MS/MS Analysis of Chondroitin Sulfate 0:53 Positive Mode LC-MS/MS Analysis of Chondroitin Sulfate Modified Glycopeptides Derived from Light and Heavy Chains of The Human Inter-α-Trypsin Inhibitor Complex. 26407992 13 56 theme confirmatory 2204:2215 arg1 information 2217:2227 confirmatory information 2204:2227 confirmatory information about the positions of glycan substituents 2204:2270 Finally, we show that the analysis of sodium adducts provides confirmatory information about the positions of glycan substituents. 26407992 1 57 theme proteoglycan 346:357 arg1 bikunin 359:365 the proteoglycan bikunin 342:365 the proteoglycan bikunin 342:365 The inter-α-trypsin inhibitor complex is a macromolecular arrangement of structurally related heavy chain proteins covalently cross-linked to the chondroitin sulfate (CS) chain of the proteoglycan bikunin. 26407992 7 58 theme anion 1239:1243 arg1 chromatography 1254:1267 strong anion exchange chromatography 1232:1267 strong anion exchange chromatography 1232:1267 The samples were trypsinized, enriched by strong anion exchange chromatography, partially depolymerized with chondroitinase ABC and analyzed by LC-MS/MS using higher-energy collisional dissociation. 26407992 11 59 theme GlcA 1840:1843 arg1 residues 1845:1852 one or two GlcA residues 1829:1852 one or two GlcA residues 1829:1852 Heavy chains H1 and H2 were identified cross-linked to GalNAc residues one or two GlcA residues apart and H1 was found linked to either the terminal or subterminal GalNAc residues. 26407992 1 60 theme related 248:254 arg1 proteins 268:275 structurally related heavy chain proteins 235:275 structurally related heavy chain proteins covalently cross-linked to the chondroitin sulfate (CS) chain of the proteoglycan bikunin 235:365 The inter-α-trypsin inhibitor complex is a macromolecular arrangement of structurally related heavy chain proteins covalently cross-linked to the chondroitin sulfate (CS) chain of the proteoglycan bikunin. 26407992 6 61 theme cross-linkage 1067:1079 arg1 region 1081:1086 heavy chain linkage and cross-linkage region 1043:1086 region 1081:1086 In this study we employed a glycoproteomics protocol to enrich and analyze light and heavy chain linkage and cross-linkage region CS glycopeptides derived from the IαI complex of human plasma, urine and cerebrospinal fluid samples. 26407992 8 62 theme linkage 1427:1433 arg1 heterogeneous 1463:1475 heterogeneous 1463:1475 heterogeneous 1463:1475 The analyses demonstrated that the CS linkage region of bikunin is highly heterogeneous. 26407992 8 62 theme linkage 1427:1433 arg1 region 1435:1440 the CS linkage region 1420:1440 the CS linkage region of bikunin 1420:1451 The analyses demonstrated that the CS linkage region of bikunin is highly heterogeneous. 26407992 3 63 theme single 535:540 arg1 chain 558:562 a single low-sulfated CS chain 533:562 a single low-sulfated CS chain of 23-55 monosaccharides with 4-9 sulfate groups 533:611 Bikunin is modified at Ser-10 by a single low-sulfated CS chain of 23-55 monosaccharides with 4-9 sulfate groups. 26407992 1 64 theme chain 262:266 arg1 proteins 268:275 structurally related heavy chain proteins 235:275 structurally related heavy chain proteins covalently cross-linked to the chondroitin sulfate (CS) chain of the proteoglycan bikunin 235:365 The inter-α-trypsin inhibitor complex is a macromolecular arrangement of structurally related heavy chain proteins covalently cross-linked to the chondroitin sulfate (CS) chain of the proteoglycan bikunin. 26407992 12 65 theme variable 1992:1999 arg1 conditions 2040:2049 variable higher-energy collisional dissociation conditions 1992:2049 variable higher-energy collisional dissociation conditions 1992:2049 The fragmentation behavior of CS glycopeptides under variable higher-energy collisional dissociation conditions displays an energy dependence that may be used to obtain complementary structural details. 26407992 6 66 theme linkage 1055:1061 arg1 glycopeptides 1091:1103 light and heavy chain linkage and cross-linkage region CS glycopeptides 1033:1103 light and heavy chain linkage and cross-linkage region CS glycopeptides derived from the IαI complex of human plasma, urine and cerebrospinal fluid samples 1033:1187 In this study we employed a glycoproteomics protocol to enrich and analyze light and heavy chain linkage and cross-linkage region CS glycopeptides derived from the IαI complex of human plasma, urine and cerebrospinal fluid samples. 26407992 13 67 theme substituents 2259:2270 arg1 positions 2239:2247 the positions 2235:2247 the positions of glycan substituents 2235:2270 Finally, we show that the analysis of sodium adducts provides confirmatory information about the positions of glycan substituents. 26407992 2 68 theme inhibitor 388:396 arg1 complex 398:404 The inter-α-trypsin inhibitor complex 368:404 The inter-α-trypsin inhibitor complex 368:404 The inter-α-trypsin inhibitor complex is abundant in plasma and associated with inflammation, kidney diseases, cancer and diabetes. 26407992 5 69 from located 817:823 arg1 end 856:858 the nonsulfated nonreducing end 828:858 the nonsulfated nonreducing end 828:858 The cross-linkage region of the bikunin CS chain is located in the nonsulfated nonreducing end, (GalNAcβ4GlcAβ3)(n), to which heavy chains (H1-H3) may be bound in GalNAc to Asp ester linkages. 26407992 5 69 from located 817:823 arg1 n 878:878 (GalNAcβ4GlcAβ3)(n) 861:879 (GalNAcβ4GlcAβ3)(n) 861:879 The cross-linkage region of the bikunin CS chain is located in the nonsulfated nonreducing end, (GalNAcβ4GlcAβ3)(n), to which heavy chains (H1-H3) may be bound in GalNAc to Asp ester linkages. 26407992 6 70 theme heavy 1043:1047 arg1 linkage 1055:1061 heavy chain linkage and cross-linkage region 1043:1086 linkage 1055:1061 In this study we employed a glycoproteomics protocol to enrich and analyze light and heavy chain linkage and cross-linkage region CS glycopeptides derived from the IαI complex of human plasma, urine and cerebrospinal fluid samples. 26407992 0 71 attach Derived 78:84 arg2 Glycopeptides 64:76 Glycopeptides 64:76 Glycopeptides Derived from Light and Heavy Chains of The Human Inter-α-Trypsin Inhibitor Complex 64:159 Positive Mode LC-MS/MS Analysis of Chondroitin Sulfate Modified Glycopeptides Derived from Light and Heavy Chains of The Human Inter-α-Trypsin Inhibitor Complex. 26407992 0 71 attach Derived 78:84 arg1 Light 91:95 Light 91:95 Light 91:95 Positive Mode LC-MS/MS Analysis of Chondroitin Sulfate Modified Glycopeptides Derived from Light and Heavy Chains of The Human Inter-α-Trypsin Inhibitor Complex. 26407992 0 71 attach Derived 78:84 arg1 Chains 107:112 Heavy Chains 101:112 Heavy Chains 101:112 Positive Mode LC-MS/MS Analysis of Chondroitin Sulfate Modified Glycopeptides Derived from Light and Heavy Chains of The Human Inter-α-Trypsin Inhibitor Complex. 26407992 6 72 theme human 1137:1141 arg1 plasma 1143:1148 human plasma 1137:1148 human plasma 1137:1148 In this study we employed a glycoproteomics protocol to enrich and analyze light and heavy chain linkage and cross-linkage region CS glycopeptides derived from the IαI complex of human plasma, urine and cerebrospinal fluid samples. 26407992 3 73 theme CS 555:556 arg1 chain 558:562 a single low-sulfated CS chain 533:562 a single low-sulfated CS chain of 23-55 monosaccharides with 4-9 sulfate groups 533:611 Bikunin is modified at Ser-10 by a single low-sulfated CS chain of 23-55 monosaccharides with 4-9 sulfate groups. 26407992 1 74 theme inhibitor 182:190 arg1 arrangement 220:230 a macromolecular arrangement 203:230 a macromolecular arrangement of structurally related heavy chain proteins covalently cross-linked to the chondroitin sulfate (CS) chain of the proteoglycan bikunin 203:365 The inter-α-trypsin inhibitor complex is a macromolecular arrangement of structurally related heavy chain proteins covalently cross-linked to the chondroitin sulfate (CS) chain of the proteoglycan bikunin. 26407992 1 74 theme inhibitor 182:190 arg1 complex 192:198 The inter-α-trypsin inhibitor complex 162:198 The inter-α-trypsin inhibitor complex 162:198 The inter-α-trypsin inhibitor complex is a macromolecular arrangement of structurally related heavy chain proteins covalently cross-linked to the chondroitin sulfate (CS) chain of the proteoglycan bikunin. 26407992 12 75 theme glycopeptides 1972:1984 arg1 behavior 1957:1964 The fragmentation behavior 1939:1964 The fragmentation behavior of CS glycopeptides under variable higher-energy collisional dissociation conditions 1939:2049 The fragmentation behavior of CS glycopeptides under variable higher-energy collisional dissociation conditions displays an energy dependence that may be used to obtain complementary structural details. 26407992 12 76 theme structural 2122:2131 arg1 details 2133:2139 complementary structural details 2108:2139 complementary structural details 2108:2139 The fragmentation behavior of CS glycopeptides under variable higher-energy collisional dissociation conditions displays an energy dependence that may be used to obtain complementary structural details. 26407992 0 77 theme Human 121:125 arg1 Complex 153:159 The Human Inter-α-Trypsin Inhibitor Complex 117:159 The Human Inter-α-Trypsin Inhibitor Complex 117:159 Positive Mode LC-MS/MS Analysis of Chondroitin Sulfate Modified Glycopeptides Derived from Light and Heavy Chains of The Human Inter-α-Trypsin Inhibitor Complex. 26407992 3 78 theme monosaccharides 573:587 arg1 chain 558:562 a single low-sulfated CS chain 533:562 a single low-sulfated CS chain of 23-55 monosaccharides with 4-9 sulfate groups 533:611 Bikunin is modified at Ser-10 by a single low-sulfated CS chain of 23-55 monosaccharides with 4-9 sulfate groups. 26407992 1 79 theme macromolecular 205:218 arg1 arrangement 220:230 a macromolecular arrangement 203:230 a macromolecular arrangement of structurally related heavy chain proteins covalently cross-linked to the chondroitin sulfate (CS) chain of the proteoglycan bikunin 203:365 The inter-α-trypsin inhibitor complex is a macromolecular arrangement of structurally related heavy chain proteins covalently cross-linked to the chondroitin sulfate (CS) chain of the proteoglycan bikunin. 26407992 1 79 theme macromolecular 205:218 arg1 complex 192:198 The inter-α-trypsin inhibitor complex 162:198 The inter-α-trypsin inhibitor complex 162:198 The inter-α-trypsin inhibitor complex is a macromolecular arrangement of structurally related heavy chain proteins covalently cross-linked to the chondroitin sulfate (CS) chain of the proteoglycan bikunin. 26407992 12 80 theme fragmentation 1943:1955 arg1 behavior 1957:1964 The fragmentation behavior 1939:1964 The fragmentation behavior of CS glycopeptides under variable higher-energy collisional dissociation conditions 1939:2049 The fragmentation behavior of CS glycopeptides under variable higher-energy collisional dissociation conditions displays an energy dependence that may be used to obtain complementary structural details. 26407992 5 81 theme heavy 891:895 arg1 H1-H3 905:909 H1-H3 905:909 H1-H3 905:909 The cross-linkage region of the bikunin CS chain is located in the nonsulfated nonreducing end, (GalNAcβ4GlcAβ3)(n), to which heavy chains (H1-H3) may be bound in GalNAc to Asp ester linkages. 26407992 5 81 theme heavy 891:895 arg1 chains 897:902 heavy chains 891:902 heavy chains (H1-H3) 891:910 The cross-linkage region of the bikunin CS chain is located in the nonsulfated nonreducing end, (GalNAcβ4GlcAβ3)(n), to which heavy chains (H1-H3) may be bound in GalNAc to Asp ester linkages. 26407992 6 82 theme CS 1088:1089 arg1 glycopeptides 1091:1103 light and heavy chain linkage and cross-linkage region CS glycopeptides 1033:1103 light and heavy chain linkage and cross-linkage region CS glycopeptides derived from the IαI complex of human plasma, urine and cerebrospinal fluid samples 1033:1187 In this study we employed a glycoproteomics protocol to enrich and analyze light and heavy chain linkage and cross-linkage region CS glycopeptides derived from the IαI complex of human plasma, urine and cerebrospinal fluid samples. 26407992 0 83 theme Inhibitor 143:151 arg1 Complex 153:159 The Human Inter-α-Trypsin Inhibitor Complex 117:159 The Human Inter-α-Trypsin Inhibitor Complex 117:159 Positive Mode LC-MS/MS Analysis of Chondroitin Sulfate Modified Glycopeptides Derived from Light and Heavy Chains of The Human Inter-α-Trypsin Inhibitor Complex. 26407992 11 84 theme GalNAc 1922:1927 arg1 residues 1929:1936 either the terminal or subterminal GalNAc residues 1887:1936 residues 1929:1936 Heavy chains H1 and H2 were identified cross-linked to GalNAc residues one or two GlcA residues apart and H1 was found linked to either the terminal or subterminal GalNAc residues. 26407992 10 85 theme novel 1616:1620 arg1 Neu5Ac 1622:1627 novel Neu5Ac and Fuc modifications 1616:1649 Neu5Ac 1622:1627 We also identified novel Neu5Ac and Fuc modifications of the linkage region as well as the presence of mono- and disialylated core 1 O-linked glycans on Thr-17. 26407992 11 86 theme GalNAc 1813:1818 arg1 residues 1820:1827 GalNAc residues 1813:1827 GalNAc residues 1813:1827 Heavy chains H1 and H2 were identified cross-linked to GalNAc residues one or two GlcA residues apart and H1 was found linked to either the terminal or subterminal GalNAc residues. 26407992 11 87 attach linked 1877:1882 arg2 H1 1864:1865 H1 1864:1865 H1 1864:1865 Heavy chains H1 and H2 were identified cross-linked to GalNAc residues one or two GlcA residues apart and H1 was found linked to either the terminal or subterminal GalNAc residues. 26407992 11 87 attach linked 1877:1882 arg1 residues 1929:1936 either the terminal or subterminal GalNAc residues 1887:1936 residues 1929:1936 Heavy chains H1 and H2 were identified cross-linked to GalNAc residues one or two GlcA residues apart and H1 was found linked to either the terminal or subterminal GalNAc residues. 26407992 10 88 theme disialylated 1710:1721 arg1 glycans 1739:1745 mono- and disialylated core 1 O-linked glycans 1700:1745 mono- and disialylated core 1 O-linked glycans 1700:1745 We also identified novel Neu5Ac and Fuc modifications of the linkage region as well as the presence of mono- and disialylated core 1 O-linked glycans on Thr-17. 26407992 6 89 theme fluid 1175:1179 arg1 samples 1181:1187 human plasma, urine and cerebrospinal fluid samples 1137:1187 human plasma, urine and cerebrospinal fluid samples 1137:1187 In this study we employed a glycoproteomics protocol to enrich and analyze light and heavy chain linkage and cross-linkage region CS glycopeptides derived from the IαI complex of human plasma, urine and cerebrospinal fluid samples. 26407992 10 90 mod modifications 1637:1649 arg1 glycans 1739:1745 mono- and disialylated core 1 O-linked glycans 1700:1745 mono- and disialylated core 1 O-linked glycans 1700:1745 We also identified novel Neu5Ac and Fuc modifications of the linkage region as well as the presence of mono- and disialylated core 1 O-linked glycans on Thr-17. 26407992 10 90 mod modifications 1637:1649 arg3 Fuc 1633:1635 novel Neu5Ac and Fuc modifications 1616:1649 Fuc 1633:1635 We also identified novel Neu5Ac and Fuc modifications of the linkage region as well as the presence of mono- and disialylated core 1 O-linked glycans on Thr-17. 26407992 10 90 mod modifications 1637:1649 arg1 region 1666:1671 the linkage region 1654:1671 the linkage region 1654:1671 We also identified novel Neu5Ac and Fuc modifications of the linkage region as well as the presence of mono- and disialylated core 1 O-linked glycans on Thr-17. 26407992 11 91 dep chains 1764:1769 arg1 H2 1778:1779 H2 1778:1779 H2 1778:1779 Heavy chains H1 and H2 were identified cross-linked to GalNAc residues one or two GlcA residues apart and H1 was found linked to either the terminal or subterminal GalNAc residues. 26407992 11 91 dep chains 1764:1769 arg1 H1 1771:1772 H1 1771:1772 H1 1771:1772 Heavy chains H1 and H2 were identified cross-linked to GalNAc residues one or two GlcA residues apart and H1 was found linked to either the terminal or subterminal GalNAc residues. 26407992 11 91 dep chains 1764:1769 arg1 chains 1764:1769 Heavy chains H1 and H2 1758:1779 Heavy chains H1 and H2 1758:1779 Heavy chains H1 and H2 were identified cross-linked to GalNAc residues one or two GlcA residues apart and H1 was found linked to either the terminal or subterminal GalNAc residues. 26407992 3 92 mod modified 511:518 arg3 chain 558:562 a single low-sulfated CS chain 533:562 a single low-sulfated CS chain of 23-55 monosaccharides with 4-9 sulfate groups 533:611 Bikunin is modified at Ser-10 by a single low-sulfated CS chain of 23-55 monosaccharides with 4-9 sulfate groups. 26407992 3 92 mod modified 511:518 arg1 Bikunin 500:506 Bikunin 500:506 Bikunin 500:506 Bikunin is modified at Ser-10 by a single low-sulfated CS chain of 23-55 monosaccharides with 4-9 sulfate groups. 26407992 13 93 theme glycan 2252:2257 arg1 substituents 2259:2270 glycan substituents 2252:2270 glycan substituents 2252:2270 Finally, we show that the analysis of sodium adducts provides confirmatory information about the positions of glycan substituents. 26407992 1 94 theme bikunin 359:365 arg1 chain 333:337 the chondroitin sulfate (CS) chain 304:337 the chondroitin sulfate (CS) chain of the proteoglycan bikunin 304:365 The inter-α-trypsin inhibitor complex is a macromolecular arrangement of structurally related heavy chain proteins covalently cross-linked to the chondroitin sulfate (CS) chain of the proteoglycan bikunin. 26407992 9 95 theme residue 1514:1520 arg1 sulfation 1493:1501 sulfation 1493:1501 sulfation of the Gal residue 1493:1520 In addition to sulfation of the Gal residue, Xyl phosphorylation was observed although exclusively in urinary samples. 26407992 0 96 theme Heavy 101:105 arg1 Chains 107:112 Heavy Chains 101:112 Heavy Chains 101:112 Positive Mode LC-MS/MS Analysis of Chondroitin Sulfate Modified Glycopeptides Derived from Light and Heavy Chains of The Human Inter-α-Trypsin Inhibitor Complex. 26407992 9 97 theme Xyl 1523:1525 arg1 phosphorylation 1527:1541 Xyl phosphorylation 1523:1541 Xyl phosphorylation 1523:1541 In addition to sulfation of the Gal residue, Xyl phosphorylation was observed although exclusively in urinary samples. 26407992 5 98 theme Asp 938:940 arg1 linkages 948:955 Asp ester linkages 938:955 Asp ester linkages 938:955 The cross-linkage region of the bikunin CS chain is located in the nonsulfated nonreducing end, (GalNAcβ4GlcAβ3)(n), to which heavy chains (H1-H3) may be bound in GalNAc to Asp ester linkages. 26407992 7 99 theme chondroitinase 1299:1312 arg1 ABC 1314:1316 chondroitinase ABC 1299:1316 chondroitinase ABC 1299:1316 The samples were trypsinized, enriched by strong anion exchange chromatography, partially depolymerized with chondroitinase ABC and analyzed by LC-MS/MS using higher-energy collisional dissociation. 26407992 6 100 gly glycopeptides 1091:1103 arg2 glycopeptides 1091:1103 light and heavy chain linkage and cross-linkage region CS glycopeptides 1033:1103 light and heavy chain linkage and cross-linkage region CS glycopeptides derived from the IαI complex of human plasma, urine and cerebrospinal fluid samples 1033:1187 In this study we employed a glycoproteomics protocol to enrich and analyze light and heavy chain linkage and cross-linkage region CS glycopeptides derived from the IαI complex of human plasma, urine and cerebrospinal fluid samples. 26407992 0 101 theme Mode 9:12 arg1 Analysis 23:30 Positive Mode LC-MS/MS Analysis 0:30 Positive Mode LC-MS/MS Analysis of Chondroitin Sulfate 0:53 Positive Mode LC-MS/MS Analysis of Chondroitin Sulfate Modified Glycopeptides Derived from Light and Heavy Chains of The Human Inter-α-Trypsin Inhibitor Complex. 26407992 10 102 theme Fuc 1633:1635 arg1 modifications 1637:1649 novel Neu5Ac and Fuc modifications 1616:1649 modifications 1637:1649 We also identified novel Neu5Ac and Fuc modifications of the linkage region as well as the presence of mono- and disialylated core 1 O-linked glycans on Thr-17. 26407992 5 103 theme nonsulfated 832:842 arg1 end 856:858 the nonsulfated nonreducing end 828:858 the nonsulfated nonreducing end 828:858 The cross-linkage region of the bikunin CS chain is located in the nonsulfated nonreducing end, (GalNAcβ4GlcAβ3)(n), to which heavy chains (H1-H3) may be bound in GalNAc to Asp ester linkages. 26407992 5 103 theme nonsulfated 832:842 arg1 n 878:878 (GalNAcβ4GlcAβ3)(n) 861:879 (GalNAcβ4GlcAβ3)(n) 861:879 The cross-linkage region of the bikunin CS chain is located in the nonsulfated nonreducing end, (GalNAcβ4GlcAβ3)(n), to which heavy chains (H1-H3) may be bound in GalNAc to Asp ester linkages. 26407992 1 104 theme sulfate 320:326 arg1 chain 333:337 the chondroitin sulfate (CS) chain 304:337 the chondroitin sulfate (CS) chain of the proteoglycan bikunin 304:365 The inter-α-trypsin inhibitor complex is a macromolecular arrangement of structurally related heavy chain proteins covalently cross-linked to the chondroitin sulfate (CS) chain of the proteoglycan bikunin. 26407992 2 105 theme kidney 462:467 arg1 diseases 469:476 kidney diseases 462:476 kidney diseases 462:476 The inter-α-trypsin inhibitor complex is abundant in plasma and associated with inflammation, kidney diseases, cancer and diabetes. 26407992 10 106 theme core 1723:1726 arg1 glycans 1739:1745 mono- and disialylated core 1 O-linked glycans 1700:1745 mono- and disialylated core 1 O-linked glycans 1700:1745 We also identified novel Neu5Ac and Fuc modifications of the linkage region as well as the presence of mono- and disialylated core 1 O-linked glycans on Thr-17. 26407992 5 107 theme CS 805:806 arg1 chain 808:812 the bikunin CS chain 793:812 the bikunin CS chain 793:812 The cross-linkage region of the bikunin CS chain is located in the nonsulfated nonreducing end, (GalNAcβ4GlcAβ3)(n), to which heavy chains (H1-H3) may be bound in GalNAc to Asp ester linkages. 26407992 12 108 theme complementary 2108:2120 arg1 details 2133:2139 complementary structural details 2108:2139 complementary structural details 2108:2139 The fragmentation behavior of CS glycopeptides under variable higher-energy collisional dissociation conditions displays an energy dependence that may be used to obtain complementary structural details. 26407992 7 109 theme exchange 1245:1252 arg1 chromatography 1254:1267 strong anion exchange chromatography 1232:1267 strong anion exchange chromatography 1232:1267 The samples were trypsinized, enriched by strong anion exchange chromatography, partially depolymerized with chondroitinase ABC and analyzed by LC-MS/MS using higher-energy collisional dissociation. 26407992 10 110 theme linkage 1658:1664 arg1 region 1666:1671 the linkage region 1654:1671 the linkage region 1654:1671 We also identified novel Neu5Ac and Fuc modifications of the linkage region as well as the presence of mono- and disialylated core 1 O-linked glycans on Thr-17. 26407992 11 111 dep found 1871:1875 arg1 linked 1877:1882 linked 1877:1882 linked to either the terminal or subterminal GalNAc residues 1877:1936 Heavy chains H1 and H2 were identified cross-linked to GalNAc residues one or two GlcA residues apart and H1 was found linked to either the terminal or subterminal GalNAc residues. 26407992 2 112 from abundant 409:416 arg1 plasma 421:426 plasma 421:426 plasma 421:426 The inter-α-trypsin inhibitor complex is abundant in plasma and associated with inflammation, kidney diseases, cancer and diabetes. 26407992 7 113 theme strong 1232:1237 arg1 chromatography 1254:1267 strong anion exchange chromatography 1232:1267 strong anion exchange chromatography 1232:1267 The samples were trypsinized, enriched by strong anion exchange chromatography, partially depolymerized with chondroitinase ABC and analyzed by LC-MS/MS using higher-energy collisional dissociation. 26407992 2 114 from plasma 421:426 arg1 abundant 409:416 abundant 409:416 abundant 409:416 The inter-α-trypsin inhibitor complex is abundant in plasma and associated with inflammation, kidney diseases, cancer and diabetes. 26407992 3 115 theme low-sulfated 542:553 arg1 chain 558:562 a single low-sulfated CS chain 533:562 a single low-sulfated CS chain of 23-55 monosaccharides with 4-9 sulfate groups 533:611 Bikunin is modified at Ser-10 by a single low-sulfated CS chain of 23-55 monosaccharides with 4-9 sulfate groups. 26407992 1 116 theme heavy 256:260 arg1 proteins 268:275 structurally related heavy chain proteins 235:275 structurally related heavy chain proteins covalently cross-linked to the chondroitin sulfate (CS) chain of the proteoglycan bikunin 235:365 The inter-α-trypsin inhibitor complex is a macromolecular arrangement of structurally related heavy chain proteins covalently cross-linked to the chondroitin sulfate (CS) chain of the proteoglycan bikunin. 26407992 12 117 theme higher-energy 2001:2013 arg1 conditions 2040:2049 variable higher-energy collisional dissociation conditions 1992:2049 variable higher-energy collisional dissociation conditions 1992:2049 The fragmentation behavior of CS glycopeptides under variable higher-energy collisional dissociation conditions displays an energy dependence that may be used to obtain complementary structural details. 26407992 8 118 theme CS 1424:1425 arg1 heterogeneous 1463:1475 heterogeneous 1463:1475 heterogeneous 1463:1475 The analyses demonstrated that the CS linkage region of bikunin is highly heterogeneous. 26407992 8 118 theme CS 1424:1425 arg1 region 1435:1440 the CS linkage region 1420:1440 the CS linkage region of bikunin 1420:1451 The analyses demonstrated that the CS linkage region of bikunin is highly heterogeneous. 26407992 12 119 gly glycopeptides 1972:1984 arg2 glycopeptides 1972:1984 CS glycopeptides 1969:1984 CS glycopeptides 1969:1984 The fragmentation behavior of CS glycopeptides under variable higher-energy collisional dissociation conditions displays an energy dependence that may be used to obtain complementary structural details. 26407992 3 120 with monosaccharides 573:587 arg1 groups 606:611 4-9 sulfate groups 594:611 4-9 sulfate groups 594:611 Bikunin is modified at Ser-10 by a single low-sulfated CS chain of 23-55 monosaccharides with 4-9 sulfate groups. 26407992 1 121 theme proteins 268:275 arg1 arrangement 220:230 a macromolecular arrangement 203:230 a macromolecular arrangement of structurally related heavy chain proteins covalently cross-linked to the chondroitin sulfate (CS) chain of the proteoglycan bikunin 203:365 The inter-α-trypsin inhibitor complex is a macromolecular arrangement of structurally related heavy chain proteins covalently cross-linked to the chondroitin sulfate (CS) chain of the proteoglycan bikunin. 26407992 1 121 theme proteins 268:275 arg1 complex 192:198 The inter-α-trypsin inhibitor complex 162:198 The inter-α-trypsin inhibitor complex 162:198 The inter-α-trypsin inhibitor complex is a macromolecular arrangement of structurally related heavy chain proteins covalently cross-linked to the chondroitin sulfate (CS) chain of the proteoglycan bikunin. 24528787 7 0 from function 759:766 arg1 plasma 799:804 nutrient-rich plasma 785:804 nutrient-rich plasma in prostate metastatic cancer cells LNCaP and non-transformed prostate epithelial cells RWPE1 785:898 METHODS The energy metabolism was examined as a function of incubation in nutrient-rich plasma in prostate metastatic cancer cells LNCaP and non-transformed prostate epithelial cells RWPE1. 24528787 8 1 theme lipophilic 961:970 arg1 Bodipy 984:989 DiD & Bodipy 978:989 DiD & Bodipy 978:989 Uptake kinetics of a fluorescent glucose analog (2-NBD) and lipophilic dyes (DiD & Bodipy) were measured in both cell lines, as well as in peripheral blood mononuclear cells (PBMC). 24528787 8 1 theme lipophilic 961:970 arg1 dyes 972:975 lipophilic dyes 961:975 lipophilic dyes (DiD & Bodipy) 961:990 Uptake kinetics of a fluorescent glucose analog (2-NBD) and lipophilic dyes (DiD & Bodipy) were measured in both cell lines, as well as in peripheral blood mononuclear cells (PBMC). 24528787 15 2 from presence 1852:1859 arg1 cells 1886:1890 LNCaP cells 1880:1890 LNCaP cells 1880:1890 The presence of lipid bodies in LNCaP cells permitted retention of Bodipy dye and allowed discrimination of LNCaP cells from PBMC with flow cytometry. 24528787 9 3 theme weight 1148:1153 arg1 proteins 1155:1162 low molecular weight proteins 1134:1162 low molecular weight proteins 1134:1162 RESULTS LNCaP cells exhibited hyper-acetylation of low molecular weight proteins compared to RWPE1 cells. 24528787 13 4 from discrimination 1662:1675 arg1 PBMC 1707:1710 PBMC 1707:1710 PBMC 1707:1710 However, the uptake rates of 2-NBD and DiD were insufficient for discrimination of LNCaP, or RWPE1 cells from PBMC. 24528787 15 5 attach presence 1852:1859 arg2 bodies 1870:1875 lipid bodies 1864:1875 lipid bodies 1864:1875 The presence of lipid bodies in LNCaP cells permitted retention of Bodipy dye and allowed discrimination of LNCaP cells from PBMC with flow cytometry. 24528787 15 5 attach presence 1852:1859 arg1 cells 1886:1890 LNCaP cells 1880:1890 LNCaP cells 1880:1890 The presence of lipid bodies in LNCaP cells permitted retention of Bodipy dye and allowed discrimination of LNCaP cells from PBMC with flow cytometry. 24528787 9 6 theme molecular 1138:1146 arg1 weight 1148:1153 low molecular weight 1134:1153 low molecular weight proteins 1134:1162 RESULTS LNCaP cells exhibited hyper-acetylation of low molecular weight proteins compared to RWPE1 cells. 24528787 17 7 theme lipid 2377:2381 arg1 bodies 2383:2388 intracellular lipid bodies 2363:2388 intracellular lipid bodies 2363:2388 However, metastatic prostate cancer cells in plasma could be clearly distinguished from blood nucleated cells due to the presence of intracellular lipid bodies. 24528787 16 8 theme lipid 2207:2211 arg1 kinetics 2220:2227 fluorescent glucose or lipid uptake kinetics 2184:2227 kinetics 2220:2227 CONCLUSIONS Despite clear differences in energy metabolism, metastatic prostate cancer cells could not be efficiently distinguished from non-transformed prostate epithelial cells using fluorescent glucose or lipid uptake kinetics. 24528787 0 9 with plasma 64:69 arg1 bodies 82:87 lipid bodies staining 76:96 lipid bodies staining 76:96 Enhanced detection of metastatic prostate cancer cells in human plasma with lipid bodies staining. 24528787 7 10 theme prostate 868:875 arg1 cells 888:892 non-transformed prostate epithelial cells 852:892 non-transformed prostate epithelial cells 852:892 METHODS The energy metabolism was examined as a function of incubation in nutrient-rich plasma in prostate metastatic cancer cells LNCaP and non-transformed prostate epithelial cells RWPE1. 24528787 8 11 theme & 982:982 arg1 Bodipy 984:989 DiD & Bodipy 978:989 DiD & Bodipy 978:989 Uptake kinetics of a fluorescent glucose analog (2-NBD) and lipophilic dyes (DiD & Bodipy) were measured in both cell lines, as well as in peripheral blood mononuclear cells (PBMC). 24528787 8 11 theme & 982:982 arg1 dyes 972:975 lipophilic dyes 961:975 lipophilic dyes (DiD & Bodipy) 961:990 Uptake kinetics of a fluorescent glucose analog (2-NBD) and lipophilic dyes (DiD & Bodipy) were measured in both cell lines, as well as in peripheral blood mononuclear cells (PBMC). 24528787 18 12 theme Fluorescent 2391:2401 arg1 labeling 2403:2410 Fluorescent labeling 2391:2410 Fluorescent labeling of lipid bodies 2391:2426 Fluorescent labeling of lipid bodies permitted a simple and sensitive means for high throughput detection of metastatic prostate cancer cells in human plasma. 24528787 16 13 theme epithelial 2161:2170 arg1 cells 2172:2176 non-transformed prostate epithelial cells 2136:2176 non-transformed prostate epithelial cells using fluorescent glucose or lipid uptake kinetics 2136:2227 CONCLUSIONS Despite clear differences in energy metabolism, metastatic prostate cancer cells could not be efficiently distinguished from non-transformed prostate epithelial cells using fluorescent glucose or lipid uptake kinetics. 24528787 14 14 theme other 1720:1724 arg1 hand 1726:1729 the other hand 1716:1729 the other hand 1716:1729 On the other hand, both RWPE1 and LNCaP cells exhibited intracellular lipid bodies following plasma incubation; whereas, PBMC did not. 24528787 9 15 theme RWPE1 1176:1180 arg1 cells 1182:1186 RWPE1 cells 1176:1186 RWPE1 cells 1176:1186 RESULTS LNCaP cells exhibited hyper-acetylation of low molecular weight proteins compared to RWPE1 cells. 24528787 2 16 theme cancer 278:283 arg1 development 285:295 cancer development 278:295 cancer development 278:295 However, not every process of cancer development is associated with competition for resources. 24528787 1 17 theme competitive 179:189 arg1 advantage 191:199 competitive advantage 179:199 competitive advantage in growth environments with limited resources 179:245 BACKGROUND Reprogramming of energy metabolism of malignant cancer cells confers competitive advantage in growth environments with limited resources. 24528787 18 18 theme throughput 2476:2485 arg1 detection 2487:2495 high throughput detection 2471:2495 high throughput detection of metastatic prostate cancer cells in human plasma 2471:2547 Fluorescent labeling of lipid bodies permitted a simple and sensitive means for high throughput detection of metastatic prostate cancer cells in human plasma. 24528787 11 19 theme O-linked 1328:1335 arg1 profiles 1358:1365 O-linked glycosylated protein profiles 1328:1365 O-linked glycosylated protein profiles 1328:1365 O-linked glycosylated protein profiles were different between LNCaP and RWPE1 cells and varied in both cell lines with plasma incubation. 24528787 6 20 contain have 638:641 arg1 questions 628:636 These questions 622:636 These questions 622:636 These questions have clinical significance, but have not yet been sufficiently examined. 24528787 6 20 contain have 638:641 arg2 significance 652:663 clinical significance 643:663 clinical significance 643:663 These questions have clinical significance, but have not yet been sufficiently examined. 24528787 18 21 theme bodies 2421:2426 arg1 labeling 2403:2410 Fluorescent labeling 2391:2410 Fluorescent labeling of lipid bodies 2391:2426 Fluorescent labeling of lipid bodies permitted a simple and sensitive means for high throughput detection of metastatic prostate cancer cells in human plasma. 24528787 15 22 theme bodies 1870:1875 arg1 presence 1852:1859 The presence 1848:1859 The presence of lipid bodies in LNCaP cells 1848:1890 The presence of lipid bodies in LNCaP cells permitted retention of Bodipy dye and allowed discrimination of LNCaP cells from PBMC with flow cytometry. 24528787 7 23 theme metastatic 818:827 arg1 cells 836:840 prostate metastatic cancer cells LNCaP and non-transformed prostate epithelial cells RWPE1 809:898 prostate metastatic cancer cells LNCaP and non-transformed prostate epithelial cells RWPE1 809:898 METHODS The energy metabolism was examined as a function of incubation in nutrient-rich plasma in prostate metastatic cancer cells LNCaP and non-transformed prostate epithelial cells RWPE1. 24528787 15 24 with PBMC 1973:1976 arg1 cytometry 1988:1996 flow cytometry 1983:1996 flow cytometry 1983:1996 The presence of lipid bodies in LNCaP cells permitted retention of Bodipy dye and allowed discrimination of LNCaP cells from PBMC with flow cytometry. 24528787 16 25 theme non-transformed 2136:2150 arg1 cells 2172:2176 non-transformed prostate epithelial cells 2136:2176 non-transformed prostate epithelial cells using fluorescent glucose or lipid uptake kinetics 2136:2227 CONCLUSIONS Despite clear differences in energy metabolism, metastatic prostate cancer cells could not be efficiently distinguished from non-transformed prostate epithelial cells using fluorescent glucose or lipid uptake kinetics. 24528787 1 26 theme limited 229:235 arg1 resources 237:245 limited resources 229:245 limited resources 229:245 BACKGROUND Reprogramming of energy metabolism of malignant cancer cells confers competitive advantage in growth environments with limited resources. 24528787 12 27 theme plasma 1578:1583 arg1 incubation 1585:1594 plasma incubation 1578:1594 plasma incubation 1578:1594 Maximal respiration or glycolytic capacities was unchanged in LNCaP cells and impaired in RWPE1 cells following plasma incubation. 24528787 18 28 theme cancer 2520:2525 arg1 cells 2527:2531 metastatic prostate cancer cells 2500:2531 metastatic prostate cancer cells 2500:2531 Fluorescent labeling of lipid bodies permitted a simple and sensitive means for high throughput detection of metastatic prostate cancer cells in human plasma. 24528787 4 29 theme cells 472:476 arg1 metabolism 451:460 energy metabolism 444:460 energy metabolism of cancer cells 444:476 Does energy metabolism of cancer cells change as a function of exposure to the bloodstream? 24528787 11 30 theme protein 1350:1356 arg1 profiles 1358:1365 O-linked glycosylated protein profiles 1328:1365 O-linked glycosylated protein profiles 1328:1365 O-linked glycosylated protein profiles were different between LNCaP and RWPE1 cells and varied in both cell lines with plasma incubation. 24528787 16 31 dep CONCLUSIONS 1999:2009 arg1 distinguished 2117:2129 distinguished 2117:2129 could not be efficiently distinguished from non-transformed prostate epithelial cells using fluorescent glucose or lipid uptake kinetics 2092:2227 CONCLUSIONS Despite clear differences in energy metabolism, metastatic prostate cancer cells could not be efficiently distinguished from non-transformed prostate epithelial cells using fluorescent glucose or lipid uptake kinetics. 24528787 17 32 theme blood 2318:2322 arg1 cells 2334:2338 blood nucleated cells 2318:2338 blood nucleated cells due to the presence of intracellular lipid bodies 2318:2388 However, metastatic prostate cancer cells in plasma could be clearly distinguished from blood nucleated cells due to the presence of intracellular lipid bodies. 24528787 15 33 from discrimination 1938:1951 arg1 PBMC 1973:1976 PBMC 1973:1976 PBMC with flow cytometry 1973:1996 The presence of lipid bodies in LNCaP cells permitted retention of Bodipy dye and allowed discrimination of LNCaP cells from PBMC with flow cytometry. 24528787 1 34 from advantage 191:199 arg1 environments 211:222 growth environments 204:222 growth environments 204:222 BACKGROUND Reprogramming of energy metabolism of malignant cancer cells confers competitive advantage in growth environments with limited resources. 24528787 1 35 theme metabolism 134:143 arg1 Reprogramming 110:122 BACKGROUND Reprogramming 99:122 BACKGROUND Reprogramming of energy metabolism of malignant cancer cells 99:169 BACKGROUND Reprogramming of energy metabolism of malignant cancer cells confers competitive advantage in growth environments with limited resources. 24528787 3 36 theme hematogenous 350:361 arg1 transport 363:371 hematogenous transport 350:371 hematogenous transport 350:371 During hematogenous transport, cancer cells are exposed to high levels of oxygen and nutrients. 24528787 4 37 theme energy 444:449 arg1 metabolism 451:460 energy metabolism 444:460 energy metabolism of cancer cells 444:476 Does energy metabolism of cancer cells change as a function of exposure to the bloodstream? 24528787 10 38 theme plasma 1199:1204 arg1 incubation 1206:1215 plasma incubation 1199:1215 plasma incubation 1199:1215 Following plasma incubation, protein lysine acetylation profile was unchanged for LNCaP cells while significantly altered for RWPE1 cells. 24528787 0 39 theme human 58:62 arg1 plasma 64:69 human plasma 58:69 human plasma with lipid bodies staining 58:96 Enhanced detection of metastatic prostate cancer cells in human plasma with lipid bodies staining. 24528787 5 40 theme such 537:540 arg1 changes 542:548 such changes 537:548 such changes 537:548 Could such changes be exploited to improve the detection of circulating tumor cells (CTC)? 24528787 1 41 theme malignant 148:156 arg1 cells 165:169 malignant cancer cells 148:169 malignant cancer cells 148:169 BACKGROUND Reprogramming of energy metabolism of malignant cancer cells confers competitive advantage in growth environments with limited resources. 24528787 4 42 theme exposure 502:509 arg1 function 490:497 a function 488:497 a function of exposure to the bloodstream 488:528 Does energy metabolism of cancer cells change as a function of exposure to the bloodstream? 24528787 13 43 theme RWPE1 1690:1694 arg1 cells 1696:1700 LNCaP, or RWPE1 cells 1680:1700 cells 1696:1700 However, the uptake rates of 2-NBD and DiD were insufficient for discrimination of LNCaP, or RWPE1 cells from PBMC. 24528787 18 44 theme sensitive 2451:2459 arg1 means 2461:2465 a simple and sensitive means 2438:2465 a simple and sensitive means for high throughput detection of metastatic prostate cancer cells in human plasma 2438:2547 Fluorescent labeling of lipid bodies permitted a simple and sensitive means for high throughput detection of metastatic prostate cancer cells in human plasma. 24528787 5 45 theme tumor 603:607 arg1 cells 609:613 circulating tumor cells 591:613 circulating tumor cells (CTC) 591:619 Could such changes be exploited to improve the detection of circulating tumor cells (CTC)? 24528787 5 45 theme tumor 603:607 arg1 CTC 616:618 CTC 616:618 CTC 616:618 Could such changes be exploited to improve the detection of circulating tumor cells (CTC)? 24528787 1 46 theme cells 165:169 arg1 metabolism 134:143 energy metabolism 127:143 energy metabolism of malignant cancer cells 127:169 BACKGROUND Reprogramming of energy metabolism of malignant cancer cells confers competitive advantage in growth environments with limited resources. 24528787 12 47 theme LNCaP 1528:1532 arg1 cells 1534:1538 LNCaP cells 1528:1538 LNCaP cells 1528:1538 Maximal respiration or glycolytic capacities was unchanged in LNCaP cells and impaired in RWPE1 cells following plasma incubation. 24528787 17 48 theme prostate 2250:2257 arg1 cells 2266:2270 metastatic prostate cancer cells 2239:2270 metastatic prostate cancer cells in plasma 2239:2280 However, metastatic prostate cancer cells in plasma could be clearly distinguished from blood nucleated cells due to the presence of intracellular lipid bodies. 24528787 15 49 theme Bodipy 1915:1920 arg1 dye 1922:1924 Bodipy dye 1915:1924 Bodipy dye 1915:1924 The presence of lipid bodies in LNCaP cells permitted retention of Bodipy dye and allowed discrimination of LNCaP cells from PBMC with flow cytometry. 24528787 10 50 theme lysine 1226:1231 arg1 acetylation 1233:1243 protein lysine acetylation 1218:1243 protein lysine acetylation profile 1218:1251 Following plasma incubation, protein lysine acetylation profile was unchanged for LNCaP cells while significantly altered for RWPE1 cells. 24528787 10 51 theme LNCaP 1271:1275 arg1 cells 1277:1281 LNCaP cells 1271:1281 LNCaP cells 1271:1281 Following plasma incubation, protein lysine acetylation profile was unchanged for LNCaP cells while significantly altered for RWPE1 cells. 24528787 8 52 theme Uptake 901:906 arg1 kinetics 908:915 Uptake kinetics 901:915 Uptake kinetics of a fluorescent glucose analog (2-NBD) and lipophilic dyes (DiD & Bodipy) 901:990 Uptake kinetics of a fluorescent glucose analog (2-NBD) and lipophilic dyes (DiD & Bodipy) were measured in both cell lines, as well as in peripheral blood mononuclear cells (PBMC). 24528787 3 53 theme high 402:405 arg1 levels 407:412 high levels 402:412 high levels of oxygen and nutrients 402:436 During hematogenous transport, cancer cells are exposed to high levels of oxygen and nutrients. 24528787 13 54 theme uptake 1610:1615 arg1 insufficient 1645:1656 insufficient 1645:1656 insufficient 1645:1656 However, the uptake rates of 2-NBD and DiD were insufficient for discrimination of LNCaP, or RWPE1 cells from PBMC. 24528787 13 54 theme uptake 1610:1615 arg1 rates 1617:1621 the uptake rates 1606:1621 the uptake rates of 2-NBD 1606:1630 However, the uptake rates of 2-NBD and DiD were insufficient for discrimination of LNCaP, or RWPE1 cells from PBMC. 24528787 0 55 theme Enhanced 0:7 arg1 detection 9:17 Enhanced detection 0:17 Enhanced detection of metastatic prostate cancer cells in human plasma with lipid bodies staining. 0:97 Enhanced detection of metastatic prostate cancer cells in human plasma with lipid bodies staining. 24528787 7 56 theme nutrient-rich 785:797 arg1 plasma 799:804 nutrient-rich plasma 785:804 nutrient-rich plasma in prostate metastatic cancer cells LNCaP and non-transformed prostate epithelial cells RWPE1 785:898 METHODS The energy metabolism was examined as a function of incubation in nutrient-rich plasma in prostate metastatic cancer cells LNCaP and non-transformed prostate epithelial cells RWPE1. 24528787 8 57 theme peripheral 1040:1049 arg1 PBMC 1076:1079 PBMC 1076:1079 PBMC 1076:1079 Uptake kinetics of a fluorescent glucose analog (2-NBD) and lipophilic dyes (DiD & Bodipy) were measured in both cell lines, as well as in peripheral blood mononuclear cells (PBMC). 24528787 8 57 theme peripheral 1040:1049 arg1 cells 1069:1073 peripheral blood mononuclear cells 1040:1073 peripheral blood mononuclear cells (PBMC) 1040:1080 Uptake kinetics of a fluorescent glucose analog (2-NBD) and lipophilic dyes (DiD & Bodipy) were measured in both cell lines, as well as in peripheral blood mononuclear cells (PBMC). 24528787 1 58 theme BACKGROUND 99:108 arg1 Reprogramming 110:122 BACKGROUND Reprogramming 99:122 BACKGROUND Reprogramming of energy metabolism of malignant cancer cells 99:169 BACKGROUND Reprogramming of energy metabolism of malignant cancer cells confers competitive advantage in growth environments with limited resources. 24528787 8 59 theme fluorescent 922:932 arg1 2-NBD 950:954 2-NBD 950:954 2-NBD 950:954 Uptake kinetics of a fluorescent glucose analog (2-NBD) and lipophilic dyes (DiD & Bodipy) were measured in both cell lines, as well as in peripheral blood mononuclear cells (PBMC). 24528787 8 59 theme fluorescent 922:932 arg1 analog 942:947 a fluorescent glucose analog 920:947 a fluorescent glucose analog (2-NBD) 920:955 Uptake kinetics of a fluorescent glucose analog (2-NBD) and lipophilic dyes (DiD & Bodipy) were measured in both cell lines, as well as in peripheral blood mononuclear cells (PBMC). 24528787 16 60 theme clear 2019:2023 arg1 differences 2025:2035 clear differences 2019:2035 clear differences in energy metabolism 2019:2056 CONCLUSIONS Despite clear differences in energy metabolism, metastatic prostate cancer cells could not be efficiently distinguished from non-transformed prostate epithelial cells using fluorescent glucose or lipid uptake kinetics. 24528787 11 61 theme plasma 1447:1452 arg1 incubation 1454:1463 plasma incubation 1447:1463 plasma incubation 1447:1463 O-linked glycosylated protein profiles were different between LNCaP and RWPE1 cells and varied in both cell lines with plasma incubation. 24528787 0 62 theme prostate 33:40 arg1 cells 49:53 metastatic prostate cancer cells 22:53 metastatic prostate cancer cells 22:53 Enhanced detection of metastatic prostate cancer cells in human plasma with lipid bodies staining. 24528787 7 63 theme incubation 771:780 arg1 function 759:766 a function 757:766 a function of incubation in nutrient-rich plasma in prostate metastatic cancer cells LNCaP and non-transformed prostate epithelial cells RWPE1 757:898 METHODS The energy metabolism was examined as a function of incubation in nutrient-rich plasma in prostate metastatic cancer cells LNCaP and non-transformed prostate epithelial cells RWPE1. 24528787 7 63 theme incubation 771:780 arg1 metabolism 730:739 The energy metabolism 719:739 The energy metabolism 719:739 METHODS The energy metabolism was examined as a function of incubation in nutrient-rich plasma in prostate metastatic cancer cells LNCaP and non-transformed prostate epithelial cells RWPE1. 24528787 8 64 theme mononuclear 1057:1067 arg1 PBMC 1076:1079 PBMC 1076:1079 PBMC 1076:1079 Uptake kinetics of a fluorescent glucose analog (2-NBD) and lipophilic dyes (DiD & Bodipy) were measured in both cell lines, as well as in peripheral blood mononuclear cells (PBMC). 24528787 8 64 theme mononuclear 1057:1067 arg1 cells 1069:1073 peripheral blood mononuclear cells 1040:1073 peripheral blood mononuclear cells (PBMC) 1040:1080 Uptake kinetics of a fluorescent glucose analog (2-NBD) and lipophilic dyes (DiD & Bodipy) were measured in both cell lines, as well as in peripheral blood mononuclear cells (PBMC). 24528787 8 65 theme analog 942:947 arg1 kinetics 908:915 Uptake kinetics 901:915 Uptake kinetics of a fluorescent glucose analog (2-NBD) and lipophilic dyes (DiD & Bodipy) 901:990 Uptake kinetics of a fluorescent glucose analog (2-NBD) and lipophilic dyes (DiD & Bodipy) were measured in both cell lines, as well as in peripheral blood mononuclear cells (PBMC). 24528787 15 66 theme LNCaP 1956:1960 arg1 cells 1962:1966 LNCaP cells 1956:1966 LNCaP cells from PBMC with flow cytometry 1956:1996 The presence of lipid bodies in LNCaP cells permitted retention of Bodipy dye and allowed discrimination of LNCaP cells from PBMC with flow cytometry. 24528787 9 67 theme LNCaP 1091:1095 arg1 cells 1097:1101 RESULTS LNCaP cells 1083:1101 RESULTS LNCaP cells 1083:1101 RESULTS LNCaP cells exhibited hyper-acetylation of low molecular weight proteins compared to RWPE1 cells. 24528787 0 68 theme cells 49:53 arg1 detection 9:17 Enhanced detection 0:17 Enhanced detection of metastatic prostate cancer cells in human plasma with lipid bodies staining. 0:97 Enhanced detection of metastatic prostate cancer cells in human plasma with lipid bodies staining. 24528787 14 69 theme LNCaP 1747:1751 arg1 cells 1753:1757 LNCaP cells 1747:1757 LNCaP cells 1747:1757 On the other hand, both RWPE1 and LNCaP cells exhibited intracellular lipid bodies following plasma incubation; whereas, PBMC did not. 24528787 7 70 dep METHODS 711:717 arg1 examined 745:752 examined 745:752 was examined as a function of incubation in nutrient-rich plasma in prostate metastatic cancer cells LNCaP and non-transformed prostate epithelial cells RWPE1 741:898 METHODS The energy metabolism was examined as a function of incubation in nutrient-rich plasma in prostate metastatic cancer cells LNCaP and non-transformed prostate epithelial cells RWPE1. 24528787 16 71 theme energy 2040:2045 arg1 metabolism 2047:2056 energy metabolism 2040:2056 energy metabolism 2040:2056 CONCLUSIONS Despite clear differences in energy metabolism, metastatic prostate cancer cells could not be efficiently distinguished from non-transformed prostate epithelial cells using fluorescent glucose or lipid uptake kinetics. 24528787 10 72 theme RWPE1 1315:1319 arg1 cells 1321:1325 RWPE1 cells 1315:1325 RWPE1 cells 1315:1325 Following plasma incubation, protein lysine acetylation profile was unchanged for LNCaP cells while significantly altered for RWPE1 cells. 24528787 12 73 theme glycolytic 1489:1498 arg1 capacities 1500:1509 glycolytic capacities 1489:1509 glycolytic capacities 1489:1509 Maximal respiration or glycolytic capacities was unchanged in LNCaP cells and impaired in RWPE1 cells following plasma incubation. 24528787 11 74 theme LNCaP 1390:1394 arg1 cells 1406:1410 LNCaP and RWPE1 cells 1390:1410 LNCaP and RWPE1 cells 1390:1410 O-linked glycosylated protein profiles were different between LNCaP and RWPE1 cells and varied in both cell lines with plasma incubation. 24528787 11 75 link O-linked 1328:1335 arg1 profiles 1358:1365 O-linked glycosylated protein profiles 1328:1365 O-linked glycosylated protein profiles 1328:1365 O-linked glycosylated protein profiles were different between LNCaP and RWPE1 cells and varied in both cell lines with plasma incubation. 24528787 8 76 theme dyes 972:975 arg1 kinetics 908:915 Uptake kinetics 901:915 Uptake kinetics of a fluorescent glucose analog (2-NBD) and lipophilic dyes (DiD & Bodipy) 901:990 Uptake kinetics of a fluorescent glucose analog (2-NBD) and lipophilic dyes (DiD & Bodipy) were measured in both cell lines, as well as in peripheral blood mononuclear cells (PBMC). 24528787 7 77 dep LNCaP 842:846 arg1 RWPE1 894:898 RWPE1 894:898 RWPE1 894:898 METHODS The energy metabolism was examined as a function of incubation in nutrient-rich plasma in prostate metastatic cancer cells LNCaP and non-transformed prostate epithelial cells RWPE1. 24528787 7 78 theme energy 723:728 arg1 function 759:766 a function 757:766 a function of incubation in nutrient-rich plasma in prostate metastatic cancer cells LNCaP and non-transformed prostate epithelial cells RWPE1 757:898 METHODS The energy metabolism was examined as a function of incubation in nutrient-rich plasma in prostate metastatic cancer cells LNCaP and non-transformed prostate epithelial cells RWPE1. 24528787 7 78 theme energy 723:728 arg1 metabolism 730:739 The energy metabolism 719:739 The energy metabolism 719:739 METHODS The energy metabolism was examined as a function of incubation in nutrient-rich plasma in prostate metastatic cancer cells LNCaP and non-transformed prostate epithelial cells RWPE1. 24528787 8 79 theme DiD 978:980 arg1 Bodipy 984:989 DiD & Bodipy 978:989 DiD & Bodipy 978:989 Uptake kinetics of a fluorescent glucose analog (2-NBD) and lipophilic dyes (DiD & Bodipy) were measured in both cell lines, as well as in peripheral blood mononuclear cells (PBMC). 24528787 8 79 theme DiD 978:980 arg1 dyes 972:975 lipophilic dyes 961:975 lipophilic dyes (DiD & Bodipy) 961:990 Uptake kinetics of a fluorescent glucose analog (2-NBD) and lipophilic dyes (DiD & Bodipy) were measured in both cell lines, as well as in peripheral blood mononuclear cells (PBMC). 24528787 17 80 theme intracellular 2363:2375 arg1 bodies 2383:2388 intracellular lipid bodies 2363:2388 intracellular lipid bodies 2363:2388 However, metastatic prostate cancer cells in plasma could be clearly distinguished from blood nucleated cells due to the presence of intracellular lipid bodies. 24528787 16 81 theme uptake 2213:2218 arg1 kinetics 2220:2227 fluorescent glucose or lipid uptake kinetics 2184:2227 kinetics 2220:2227 CONCLUSIONS Despite clear differences in energy metabolism, metastatic prostate cancer cells could not be efficiently distinguished from non-transformed prostate epithelial cells using fluorescent glucose or lipid uptake kinetics. 24528787 9 82 theme proteins 1155:1162 arg1 hyper-acetylation 1113:1129 hyper-acetylation 1113:1129 hyper-acetylation of low molecular weight proteins 1113:1162 RESULTS LNCaP cells exhibited hyper-acetylation of low molecular weight proteins compared to RWPE1 cells. 24528787 16 83 from differences 2025:2035 arg1 metabolism 2047:2056 energy metabolism 2040:2056 energy metabolism 2040:2056 CONCLUSIONS Despite clear differences in energy metabolism, metastatic prostate cancer cells could not be efficiently distinguished from non-transformed prostate epithelial cells using fluorescent glucose or lipid uptake kinetics. 24528787 15 84 theme cells 1962:1966 arg1 discrimination 1938:1951 discrimination 1938:1951 discrimination of LNCaP cells from PBMC with flow cytometry 1938:1996 The presence of lipid bodies in LNCaP cells permitted retention of Bodipy dye and allowed discrimination of LNCaP cells from PBMC with flow cytometry. 24528787 17 85 theme bodies 2383:2388 arg1 presence 2351:2358 the presence 2347:2358 the presence of intracellular lipid bodies 2347:2388 However, metastatic prostate cancer cells in plasma could be clearly distinguished from blood nucleated cells due to the presence of intracellular lipid bodies. 24528787 11 86 theme RWPE1 1400:1404 arg1 cells 1406:1410 LNCaP and RWPE1 cells 1390:1410 LNCaP and RWPE1 cells 1390:1410 O-linked glycosylated protein profiles were different between LNCaP and RWPE1 cells and varied in both cell lines with plasma incubation. 24528787 2 87 theme development 285:295 arg1 process 267:273 not every process 257:273 not every process of cancer development 257:295 However, not every process of cancer development is associated with competition for resources. 24528787 7 88 theme epithelial 877:886 arg1 cells 888:892 non-transformed prostate epithelial cells 852:892 non-transformed prostate epithelial cells 852:892 METHODS The energy metabolism was examined as a function of incubation in nutrient-rich plasma in prostate metastatic cancer cells LNCaP and non-transformed prostate epithelial cells RWPE1. 24528787 7 89 from plasma 799:804 arg1 cells 836:840 prostate metastatic cancer cells LNCaP and non-transformed prostate epithelial cells RWPE1 809:898 prostate metastatic cancer cells LNCaP and non-transformed prostate epithelial cells RWPE1 809:898 METHODS The energy metabolism was examined as a function of incubation in nutrient-rich plasma in prostate metastatic cancer cells LNCaP and non-transformed prostate epithelial cells RWPE1. 24528787 15 90 theme LNCaP 1880:1884 arg1 cells 1886:1890 LNCaP cells 1880:1890 LNCaP cells 1880:1890 The presence of lipid bodies in LNCaP cells permitted retention of Bodipy dye and allowed discrimination of LNCaP cells from PBMC with flow cytometry. 24528787 14 91 theme lipid 1783:1787 arg1 bodies 1789:1794 intracellular lipid bodies 1769:1794 intracellular lipid bodies 1769:1794 On the other hand, both RWPE1 and LNCaP cells exhibited intracellular lipid bodies following plasma incubation; whereas, PBMC did not. 24528787 7 92 theme non-transformed 852:866 arg1 cells 888:892 non-transformed prostate epithelial cells 852:892 non-transformed prostate epithelial cells 852:892 METHODS The energy metabolism was examined as a function of incubation in nutrient-rich plasma in prostate metastatic cancer cells LNCaP and non-transformed prostate epithelial cells RWPE1. 24528787 12 93 from unchanged 1515:1523 arg1 cells 1534:1538 LNCaP cells 1528:1538 LNCaP cells 1528:1538 Maximal respiration or glycolytic capacities was unchanged in LNCaP cells and impaired in RWPE1 cells following plasma incubation. 24528787 18 94 theme prostate 2511:2518 arg1 cells 2527:2531 metastatic prostate cancer cells 2500:2531 metastatic prostate cancer cells 2500:2531 Fluorescent labeling of lipid bodies permitted a simple and sensitive means for high throughput detection of metastatic prostate cancer cells in human plasma. 24528787 15 95 theme lipid 1864:1868 arg1 bodies 1870:1875 lipid bodies 1864:1875 lipid bodies 1864:1875 The presence of lipid bodies in LNCaP cells permitted retention of Bodipy dye and allowed discrimination of LNCaP cells from PBMC with flow cytometry. 24528787 1 96 theme growth 204:209 arg1 environments 211:222 growth environments 204:222 growth environments 204:222 BACKGROUND Reprogramming of energy metabolism of malignant cancer cells confers competitive advantage in growth environments with limited resources. 24528787 4 97 theme cancer 465:470 arg1 cells 472:476 cancer cells 465:476 cancer cells 465:476 Does energy metabolism of cancer cells change as a function of exposure to the bloodstream? 24528787 14 98 theme plasma 1806:1811 arg1 incubation 1813:1822 plasma incubation 1806:1822 plasma incubation 1806:1822 On the other hand, both RWPE1 and LNCaP cells exhibited intracellular lipid bodies following plasma incubation; whereas, PBMC did not. 24528787 16 99 theme prostate 2152:2159 arg1 cells 2172:2176 non-transformed prostate epithelial cells 2136:2176 non-transformed prostate epithelial cells using fluorescent glucose or lipid uptake kinetics 2136:2227 CONCLUSIONS Despite clear differences in energy metabolism, metastatic prostate cancer cells could not be efficiently distinguished from non-transformed prostate epithelial cells using fluorescent glucose or lipid uptake kinetics. 24528787 7 100 theme cancer 829:834 arg1 cells 836:840 prostate metastatic cancer cells LNCaP and non-transformed prostate epithelial cells RWPE1 809:898 prostate metastatic cancer cells LNCaP and non-transformed prostate epithelial cells RWPE1 809:898 METHODS The energy metabolism was examined as a function of incubation in nutrient-rich plasma in prostate metastatic cancer cells LNCaP and non-transformed prostate epithelial cells RWPE1. 24528787 11 101 theme glycosylated 1337:1348 arg1 profiles 1358:1365 O-linked glycosylated protein profiles 1328:1365 O-linked glycosylated protein profiles 1328:1365 O-linked glycosylated protein profiles were different between LNCaP and RWPE1 cells and varied in both cell lines with plasma incubation. 24528787 18 102 theme high 2471:2474 arg1 detection 2487:2495 high throughput detection 2471:2495 high throughput detection of metastatic prostate cancer cells in human plasma 2471:2547 Fluorescent labeling of lipid bodies permitted a simple and sensitive means for high throughput detection of metastatic prostate cancer cells in human plasma. 24528787 16 103 theme prostate 2070:2077 arg1 cells 2086:2090 metastatic prostate cancer cells 2059:2090 metastatic prostate cancer cells 2059:2090 CONCLUSIONS Despite clear differences in energy metabolism, metastatic prostate cancer cells could not be efficiently distinguished from non-transformed prostate epithelial cells using fluorescent glucose or lipid uptake kinetics. 24528787 10 104 theme protein 1218:1224 arg1 acetylation 1233:1243 protein lysine acetylation 1218:1243 protein lysine acetylation profile 1218:1251 Following plasma incubation, protein lysine acetylation profile was unchanged for LNCaP cells while significantly altered for RWPE1 cells. 24528787 11 105 gly glycosylated 1337:1348 arg1 profiles 1358:1365 O-linked glycosylated protein profiles 1328:1365 O-linked glycosylated protein profiles 1328:1365 O-linked glycosylated protein profiles were different between LNCaP and RWPE1 cells and varied in both cell lines with plasma incubation. 24528787 1 106 theme energy 127:132 arg1 metabolism 134:143 energy metabolism 127:143 energy metabolism of malignant cancer cells 127:169 BACKGROUND Reprogramming of energy metabolism of malignant cancer cells confers competitive advantage in growth environments with limited resources. 24528787 12 107 theme RWPE1 1556:1560 arg1 cells 1562:1566 RWPE1 cells 1556:1566 RWPE1 cells 1556:1566 Maximal respiration or glycolytic capacities was unchanged in LNCaP cells and impaired in RWPE1 cells following plasma incubation. 24528787 17 108 theme nucleated 2324:2332 arg1 cells 2334:2338 blood nucleated cells 2318:2338 blood nucleated cells due to the presence of intracellular lipid bodies 2318:2388 However, metastatic prostate cancer cells in plasma could be clearly distinguished from blood nucleated cells due to the presence of intracellular lipid bodies. 24528787 6 109 theme clinical 643:650 arg1 significance 652:663 clinical significance 643:663 clinical significance 643:663 These questions have clinical significance, but have not yet been sufficiently examined. 24528787 17 110 from cells 2266:2270 arg1 plasma 2275:2280 plasma 2275:2280 plasma 2275:2280 However, metastatic prostate cancer cells in plasma could be clearly distinguished from blood nucleated cells due to the presence of intracellular lipid bodies. 24528787 18 111 theme human 2536:2540 arg1 plasma 2542:2547 human plasma 2536:2547 human plasma 2536:2547 Fluorescent labeling of lipid bodies permitted a simple and sensitive means for high throughput detection of metastatic prostate cancer cells in human plasma. 24528787 0 112 theme lipid 76:80 arg1 bodies 82:87 lipid bodies staining 76:96 lipid bodies staining 76:96 Enhanced detection of metastatic prostate cancer cells in human plasma with lipid bodies staining. 24528787 8 113 theme cell 1014:1017 arg1 lines 1019:1023 both cell lines 1009:1023 both cell lines 1009:1023 Uptake kinetics of a fluorescent glucose analog (2-NBD) and lipophilic dyes (DiD & Bodipy) were measured in both cell lines, as well as in peripheral blood mononuclear cells (PBMC). 24528787 1 114 theme cancer 158:163 arg1 cells 165:169 malignant cancer cells 148:169 malignant cancer cells 148:169 BACKGROUND Reprogramming of energy metabolism of malignant cancer cells confers competitive advantage in growth environments with limited resources. 24528787 0 115 from detection 9:17 arg1 plasma 64:69 human plasma 58:69 human plasma with lipid bodies staining 58:96 Enhanced detection of metastatic prostate cancer cells in human plasma with lipid bodies staining. 24528787 13 116 theme cells 1696:1700 arg1 discrimination 1662:1675 discrimination 1662:1675 discrimination of LNCaP, or RWPE1 cells from PBMC 1662:1710 However, the uptake rates of 2-NBD and DiD were insufficient for discrimination of LNCaP, or RWPE1 cells from PBMC. 24528787 18 117 theme metastatic 2500:2509 arg1 cells 2527:2531 metastatic prostate cancer cells 2500:2531 metastatic prostate cancer cells 2500:2531 Fluorescent labeling of lipid bodies permitted a simple and sensitive means for high throughput detection of metastatic prostate cancer cells in human plasma. 24528787 16 118 theme metastatic 2059:2068 arg1 cells 2086:2090 metastatic prostate cancer cells 2059:2090 metastatic prostate cancer cells 2059:2090 CONCLUSIONS Despite clear differences in energy metabolism, metastatic prostate cancer cells could not be efficiently distinguished from non-transformed prostate epithelial cells using fluorescent glucose or lipid uptake kinetics. 24528787 10 119 theme acetylation 1233:1243 arg1 profile 1245:1251 protein lysine acetylation profile 1218:1251 protein lysine acetylation profile 1218:1251 Following plasma incubation, protein lysine acetylation profile was unchanged for LNCaP cells while significantly altered for RWPE1 cells. 24528787 15 120 from PBMC 1973:1976 arg1 discrimination 1938:1951 discrimination 1938:1951 discrimination of LNCaP cells from PBMC with flow cytometry 1938:1996 The presence of lipid bodies in LNCaP cells permitted retention of Bodipy dye and allowed discrimination of LNCaP cells from PBMC with flow cytometry. 24528787 15 120 from PBMC 1973:1976 arg1 cells 1962:1966 LNCaP cells 1956:1966 LNCaP cells from PBMC with flow cytometry 1956:1996 The presence of lipid bodies in LNCaP cells permitted retention of Bodipy dye and allowed discrimination of LNCaP cells from PBMC with flow cytometry. 24528787 0 121 theme staining 89:96 arg1 bodies 82:87 lipid bodies staining 76:96 lipid bodies staining 76:96 Enhanced detection of metastatic prostate cancer cells in human plasma with lipid bodies staining. 24528787 5 122 theme cells 609:613 arg1 detection 578:586 the detection 574:586 the detection of circulating tumor cells (CTC) 574:619 Could such changes be exploited to improve the detection of circulating tumor cells (CTC)? 24528787 18 123 theme lipid 2415:2419 arg1 bodies 2421:2426 lipid bodies 2415:2426 lipid bodies 2415:2426 Fluorescent labeling of lipid bodies permitted a simple and sensitive means for high throughput detection of metastatic prostate cancer cells in human plasma. 24528787 17 124 theme cancer 2259:2264 arg1 cells 2266:2270 metastatic prostate cancer cells 2239:2270 metastatic prostate cancer cells in plasma 2239:2280 However, metastatic prostate cancer cells in plasma could be clearly distinguished from blood nucleated cells due to the presence of intracellular lipid bodies. 24528787 15 125 theme dye 1922:1924 arg1 retention 1902:1910 retention 1902:1910 retention of Bodipy dye 1902:1924 The presence of lipid bodies in LNCaP cells permitted retention of Bodipy dye and allowed discrimination of LNCaP cells from PBMC with flow cytometry. 24528787 11 126 theme cell 1431:1434 arg1 lines 1436:1440 both cell lines 1426:1440 both cell lines 1426:1440 O-linked glycosylated protein profiles were different between LNCaP and RWPE1 cells and varied in both cell lines with plasma incubation. 24528787 3 127 theme cancer 374:379 arg1 cells 381:385 cancer cells 374:385 cancer cells 374:385 During hematogenous transport, cancer cells are exposed to high levels of oxygen and nutrients. 24528787 13 128 theme LNCaP 1680:1684 arg1 discrimination 1662:1675 discrimination 1662:1675 discrimination of LNCaP, or RWPE1 cells from PBMC 1662:1710 However, the uptake rates of 2-NBD and DiD were insufficient for discrimination of LNCaP, or RWPE1 cells from PBMC. 24528787 12 129 from cells 1534:1538 arg1 unchanged 1515:1523 unchanged 1515:1523 unchanged 1515:1523 Maximal respiration or glycolytic capacities was unchanged in LNCaP cells and impaired in RWPE1 cells following plasma incubation. 24528787 16 130 theme fluorescent 2184:2194 arg1 glucose 2196:2202 fluorescent glucose or lipid uptake kinetics 2184:2227 glucose 2196:2202 CONCLUSIONS Despite clear differences in energy metabolism, metastatic prostate cancer cells could not be efficiently distinguished from non-transformed prostate epithelial cells using fluorescent glucose or lipid uptake kinetics. 24528787 18 131 theme cells 2527:2531 arg1 detection 2487:2495 high throughput detection 2471:2495 high throughput detection of metastatic prostate cancer cells in human plasma 2471:2547 Fluorescent labeling of lipid bodies permitted a simple and sensitive means for high throughput detection of metastatic prostate cancer cells in human plasma. 24528787 0 132 theme metastatic 22:31 arg1 cells 49:53 metastatic prostate cancer cells 22:53 metastatic prostate cancer cells 22:53 Enhanced detection of metastatic prostate cancer cells in human plasma with lipid bodies staining. 24528787 7 133 theme prostate 809:816 arg1 cells 836:840 prostate metastatic cancer cells LNCaP and non-transformed prostate epithelial cells RWPE1 809:898 prostate metastatic cancer cells LNCaP and non-transformed prostate epithelial cells RWPE1 809:898 METHODS The energy metabolism was examined as a function of incubation in nutrient-rich plasma in prostate metastatic cancer cells LNCaP and non-transformed prostate epithelial cells RWPE1. 24528787 8 134 theme blood 1051:1055 arg1 PBMC 1076:1079 PBMC 1076:1079 PBMC 1076:1079 Uptake kinetics of a fluorescent glucose analog (2-NBD) and lipophilic dyes (DiD & Bodipy) were measured in both cell lines, as well as in peripheral blood mononuclear cells (PBMC). 24528787 8 134 theme blood 1051:1055 arg1 cells 1069:1073 peripheral blood mononuclear cells 1040:1073 peripheral blood mononuclear cells (PBMC) 1040:1080 Uptake kinetics of a fluorescent glucose analog (2-NBD) and lipophilic dyes (DiD & Bodipy) were measured in both cell lines, as well as in peripheral blood mononuclear cells (PBMC). 24528787 5 135 theme circulating 591:601 arg1 cells 609:613 circulating tumor cells 591:613 circulating tumor cells (CTC) 591:619 Could such changes be exploited to improve the detection of circulating tumor cells (CTC)? 24528787 5 135 theme circulating 591:601 arg1 CTC 616:618 CTC 616:618 CTC 616:618 Could such changes be exploited to improve the detection of circulating tumor cells (CTC)? 24528787 15 136 theme flow 1983:1986 arg1 cytometry 1988:1996 flow cytometry 1983:1996 flow cytometry 1983:1996 The presence of lipid bodies in LNCaP cells permitted retention of Bodipy dye and allowed discrimination of LNCaP cells from PBMC with flow cytometry. 24528787 0 137 theme cancer 42:47 arg1 cells 49:53 metastatic prostate cancer cells 22:53 metastatic prostate cancer cells 22:53 Enhanced detection of metastatic prostate cancer cells in human plasma with lipid bodies staining. 24528787 14 138 theme intracellular 1769:1781 arg1 bodies 1789:1794 intracellular lipid bodies 1769:1794 intracellular lipid bodies 1769:1794 On the other hand, both RWPE1 and LNCaP cells exhibited intracellular lipid bodies following plasma incubation; whereas, PBMC did not. 24528787 3 139 theme nutrients 428:436 arg1 levels 407:412 high levels 402:412 high levels of oxygen and nutrients 402:436 During hematogenous transport, cancer cells are exposed to high levels of oxygen and nutrients. 24528787 18 140 theme simple 2440:2445 arg1 means 2461:2465 a simple and sensitive means 2438:2465 a simple and sensitive means for high throughput detection of metastatic prostate cancer cells in human plasma 2438:2547 Fluorescent labeling of lipid bodies permitted a simple and sensitive means for high throughput detection of metastatic prostate cancer cells in human plasma. 24528787 9 141 theme RESULTS 1083:1089 arg1 cells 1097:1101 RESULTS LNCaP cells 1083:1101 RESULTS LNCaP cells 1083:1101 RESULTS LNCaP cells exhibited hyper-acetylation of low molecular weight proteins compared to RWPE1 cells. 24528787 13 142 from PBMC 1707:1710 arg1 cells 1696:1700 LNCaP, or RWPE1 cells 1680:1700 cells 1696:1700 However, the uptake rates of 2-NBD and DiD were insufficient for discrimination of LNCaP, or RWPE1 cells from PBMC. 24528787 13 142 from PBMC 1707:1710 arg1 LNCaP 1680:1684 LNCaP, or RWPE1 cells 1680:1700 LNCaP 1680:1684 However, the uptake rates of 2-NBD and DiD were insufficient for discrimination of LNCaP, or RWPE1 cells from PBMC. 24528787 13 142 from PBMC 1707:1710 arg1 discrimination 1662:1675 discrimination 1662:1675 discrimination of LNCaP, or RWPE1 cells from PBMC 1662:1710 However, the uptake rates of 2-NBD and DiD were insufficient for discrimination of LNCaP, or RWPE1 cells from PBMC. 24528787 1 143 with advantage 191:199 arg1 resources 237:245 limited resources 229:245 limited resources 229:245 BACKGROUND Reprogramming of energy metabolism of malignant cancer cells confers competitive advantage in growth environments with limited resources. 24528787 8 144 theme glucose 934:940 arg1 2-NBD 950:954 2-NBD 950:954 2-NBD 950:954 Uptake kinetics of a fluorescent glucose analog (2-NBD) and lipophilic dyes (DiD & Bodipy) were measured in both cell lines, as well as in peripheral blood mononuclear cells (PBMC). 24528787 8 144 theme glucose 934:940 arg1 analog 942:947 a fluorescent glucose analog 920:947 a fluorescent glucose analog (2-NBD) 920:955 Uptake kinetics of a fluorescent glucose analog (2-NBD) and lipophilic dyes (DiD & Bodipy) were measured in both cell lines, as well as in peripheral blood mononuclear cells (PBMC). 24528787 3 145 theme oxygen 417:422 arg1 levels 407:412 high levels 402:412 high levels of oxygen and nutrients 402:436 During hematogenous transport, cancer cells are exposed to high levels of oxygen and nutrients. 24528787 13 146 theme 2-NBD 1626:1630 arg1 insufficient 1645:1656 insufficient 1645:1656 insufficient 1645:1656 However, the uptake rates of 2-NBD and DiD were insufficient for discrimination of LNCaP, or RWPE1 cells from PBMC. 24528787 13 146 theme 2-NBD 1626:1630 arg1 rates 1617:1621 the uptake rates 1606:1621 the uptake rates of 2-NBD 1606:1630 However, the uptake rates of 2-NBD and DiD were insufficient for discrimination of LNCaP, or RWPE1 cells from PBMC. 24528787 16 147 theme cancer 2079:2084 arg1 cells 2086:2090 metastatic prostate cancer cells 2059:2090 metastatic prostate cancer cells 2059:2090 CONCLUSIONS Despite clear differences in energy metabolism, metastatic prostate cancer cells could not be efficiently distinguished from non-transformed prostate epithelial cells using fluorescent glucose or lipid uptake kinetics. 24528787 17 148 theme metastatic 2239:2248 arg1 cells 2266:2270 metastatic prostate cancer cells 2239:2270 metastatic prostate cancer cells in plasma 2239:2280 However, metastatic prostate cancer cells in plasma could be clearly distinguished from blood nucleated cells due to the presence of intracellular lipid bodies. 24528787 12 149 theme Maximal 1466:1472 arg1 respiration 1474:1484 Maximal respiration 1466:1484 Maximal respiration 1466:1484 Maximal respiration or glycolytic capacities was unchanged in LNCaP cells and impaired in RWPE1 cells following plasma incubation. 24528787 18 150 from detection 2487:2495 arg1 plasma 2542:2547 human plasma 2536:2547 human plasma 2536:2547 Fluorescent labeling of lipid bodies permitted a simple and sensitive means for high throughput detection of metastatic prostate cancer cells in human plasma. 24528787 7 151 dep cells 836:840 arg1 cells 888:892 non-transformed prostate epithelial cells 852:892 non-transformed prostate epithelial cells 852:892 METHODS The energy metabolism was examined as a function of incubation in nutrient-rich plasma in prostate metastatic cancer cells LNCaP and non-transformed prostate epithelial cells RWPE1. 24528787 7 151 dep cells 836:840 arg1 LNCaP 842:846 LNCaP 842:846 LNCaP 842:846 METHODS The energy metabolism was examined as a function of incubation in nutrient-rich plasma in prostate metastatic cancer cells LNCaP and non-transformed prostate epithelial cells RWPE1. 24528787 17 152 theme due 2340:2342 arg1 cells 2334:2338 blood nucleated cells 2318:2338 blood nucleated cells due to the presence of intracellular lipid bodies 2318:2388 However, metastatic prostate cancer cells in plasma could be clearly distinguished from blood nucleated cells due to the presence of intracellular lipid bodies. 24528787 9 153 theme low 1134:1136 arg1 weight 1148:1153 low molecular weight 1134:1153 low molecular weight proteins 1134:1162 RESULTS LNCaP cells exhibited hyper-acetylation of low molecular weight proteins compared to RWPE1 cells. 28676677 0 0 theme CD8+ 88:91 arg1 cells 95:99 Human CD8+ T cells 82:99 Human CD8+ T cells 82:99 HLA-E Presents Glycopeptides from the Mycobacterium tuberculosis Protein MPT32 to Human CD8+ T cells. 28676677 6 1 theme CD8+ 945:948 arg1 response 964:971 an HLA-E specific CD8+ T cell immune response 927:971 an HLA-E specific CD8+ T cell immune response 927:971 This is the first description of a post-translationally modified Mtb-derived protein antigen presented in the context of an HLA-E specific CD8+ T cell immune response. 28676677 5 2 theme N-terminal 709:718 arg1 mannosylation 729:741 N-terminal O-linked mannosylation 709:741 N-terminal O-linked mannosylation of MPT32 by a mannosyltransferase encoded by the Rv1002c gene 709:803 Recognition by the CD8+ T cell clone required N-terminal O-linked mannosylation of MPT32 by a mannosyltransferase encoded by the Rv1002c gene. 28676677 0 3 theme Human 82:86 arg1 cells 95:99 Human CD8+ T cells 82:99 Human CD8+ T cells 82:99 HLA-E Presents Glycopeptides from the Mycobacterium tuberculosis Protein MPT32 to Human CD8+ T cells. 28676677 6 4 theme first 818:822 arg1 description 824:834 the first description 814:834 the first description of a post-translationally modified Mtb-derived protein antigen presented in the context of an HLA-E specific CD8+ T cell immune response 814:971 This is the first description of a post-translationally modified Mtb-derived protein antigen presented in the context of an HLA-E specific CD8+ T cell immune response. 28676677 6 4 theme first 818:822 arg1 This 806:809 This 806:809 This 806:809 This is the first description of a post-translationally modified Mtb-derived protein antigen presented in the context of an HLA-E specific CD8+ T cell immune response. 28676677 4 5 theme cell 560:563 arg1 clone 565:569 an HLA-E-restricted CD8+ T cell clone 533:569 an HLA-E-restricted CD8+ T cell clone isolated from an Mtb latently infected individual 533:619 In this manuscript, we identified the antigen recognized by an HLA-E-restricted CD8+ T cell clone isolated from an Mtb latently infected individual as a peptide from the Mtb protein, MPT32. 28676677 5 6 theme cell 689:692 arg1 clone 694:698 the CD8+ T cell clone 678:698 the CD8+ T cell clone 678:698 Recognition by the CD8+ T cell clone required N-terminal O-linked mannosylation of MPT32 by a mannosyltransferase encoded by the Rv1002c gene. 28676677 6 7 theme antigen 891:897 arg1 description 824:834 the first description 814:834 the first description of a post-translationally modified Mtb-derived protein antigen presented in the context of an HLA-E specific CD8+ T cell immune response 814:971 This is the first description of a post-translationally modified Mtb-derived protein antigen presented in the context of an HLA-E specific CD8+ T cell immune response. 28676677 6 7 theme antigen 891:897 arg1 This 806:809 This 806:809 This 806:809 This is the first description of a post-translationally modified Mtb-derived protein antigen presented in the context of an HLA-E specific CD8+ T cell immune response. 28676677 7 8 theme practical 1086:1094 arg1 impact 1096:1101 practical impact 1086:1101 practical impact 1086:1101 The identification of an immune response that targets a unique mycobacterial modification is novel and may have practical impact in the development of vaccines and diagnostics. 28676677 5 9 gly mannosylation 729:741 arg1 MPT32 746:750 MPT32 746:750 MPT32 746:750 Recognition by the CD8+ T cell clone required N-terminal O-linked mannosylation of MPT32 by a mannosyltransferase encoded by the Rv1002c gene. 28676677 6 10 theme response 964:971 arg1 context 916:922 the context 912:922 the context of an HLA-E specific CD8+ T cell immune response 912:971 This is the first description of a post-translationally modified Mtb-derived protein antigen presented in the context of an HLA-E specific CD8+ T cell immune response. 28676677 0 11 theme T 93:93 arg1 cells 95:99 Human CD8+ T cells 82:99 Human CD8+ T cells 82:99 HLA-E Presents Glycopeptides from the Mycobacterium tuberculosis Protein MPT32 to Human CD8+ T cells. 28676677 6 12 theme protein 883:889 arg1 antigen 891:897 a post-translationally modified Mtb-derived protein antigen 839:897 a post-translationally modified Mtb-derived protein antigen presented in the context of an HLA-E specific CD8+ T cell immune response 839:971 This is the first description of a post-translationally modified Mtb-derived protein antigen presented in the context of an HLA-E specific CD8+ T cell immune response. 28676677 7 13 theme vaccines 1125:1132 arg1 development 1110:1120 the development 1106:1120 the development of vaccines and diagnostics 1106:1148 The identification of an immune response that targets a unique mycobacterial modification is novel and may have practical impact in the development of vaccines and diagnostics. 28676677 2 14 theme T 287:287 arg1 cells 289:293 Both classically and non-classically restricted cytotoxic CD8+ T cells 224:293 Both classically and non-classically restricted cytotoxic CD8+ T cells 224:293 Both classically and non-classically restricted cytotoxic CD8+ T cells are important to the control of Mtb infection. 28676677 4 15 from protein 647:653 arg1 peptide 626:632 a peptide 624:632 a peptide from the Mtb protein, MPT32 624:660 In this manuscript, we identified the antigen recognized by an HLA-E-restricted CD8+ T cell clone isolated from an Mtb latently infected individual as a peptide from the Mtb protein, MPT32. 28676677 4 15 from protein 647:653 arg1 antigen 511:517 the antigen 507:517 the antigen recognized by an HLA-E-restricted CD8+ T cell clone isolated from an Mtb latently infected individual 507:619 In this manuscript, we identified the antigen recognized by an HLA-E-restricted CD8+ T cell clone isolated from an Mtb latently infected individual as a peptide from the Mtb protein, MPT32. 28676677 6 16 theme immune 957:962 arg1 response 964:971 an HLA-E specific CD8+ T cell immune response 927:971 an HLA-E specific CD8+ T cell immune response 927:971 This is the first description of a post-translationally modified Mtb-derived protein antigen presented in the context of an HLA-E specific CD8+ T cell immune response. 28676677 5 17 theme MPT32 746:750 arg1 mannosylation 729:741 N-terminal O-linked mannosylation 709:741 N-terminal O-linked mannosylation of MPT32 by a mannosyltransferase encoded by the Rv1002c gene 709:803 Recognition by the CD8+ T cell clone required N-terminal O-linked mannosylation of MPT32 by a mannosyltransferase encoded by the Rv1002c gene. 28676677 3 18 dep molecule 403:410 arg1 HLA-E 412:416 HLA-E 412:416 the non-classical MHC I molecule HLA-E 379:416 We and others have demonstrated that the non-classical MHC I molecule HLA-E can present pathogen-derived peptides to CD8+ T cells. 28676677 2 19 theme CD8+ 282:285 arg1 cells 289:293 Both classically and non-classically restricted cytotoxic CD8+ T cells 224:293 Both classically and non-classically restricted cytotoxic CD8+ T cells 224:293 Both classically and non-classically restricted cytotoxic CD8+ T cells are important to the control of Mtb infection. 28676677 0 20 theme tuberculosis 52:63 arg1 MPT32 73:77 the Mycobacterium tuberculosis Protein MPT32 34:77 the Mycobacterium tuberculosis Protein MPT32 to Human CD8+ T cells 34:99 HLA-E Presents Glycopeptides from the Mycobacterium tuberculosis Protein MPT32 to Human CD8+ T cells. 28676677 6 21 theme modified 862:869 arg1 antigen 891:897 a post-translationally modified Mtb-derived protein antigen 839:897 a post-translationally modified Mtb-derived protein antigen presented in the context of an HLA-E specific CD8+ T cell immune response 839:971 This is the first description of a post-translationally modified Mtb-derived protein antigen presented in the context of an HLA-E specific CD8+ T cell immune response. 28676677 3 22 theme I 401:401 arg1 molecule 403:410 the non-classical MHC I molecule 379:410 the non-classical MHC I molecule HLA-E 379:416 We and others have demonstrated that the non-classical MHC I molecule HLA-E can present pathogen-derived peptides to CD8+ T cells. 28676677 2 23 theme cytotoxic 272:280 arg1 cells 289:293 Both classically and non-classically restricted cytotoxic CD8+ T cells 224:293 Both classically and non-classically restricted cytotoxic CD8+ T cells 224:293 Both classically and non-classically restricted cytotoxic CD8+ T cells are important to the control of Mtb infection. 28676677 3 24 theme pathogen-derived 430:445 arg1 peptides 447:454 pathogen-derived peptides 430:454 pathogen-derived peptides 430:454 We and others have demonstrated that the non-classical MHC I molecule HLA-E can present pathogen-derived peptides to CD8+ T cells. 28676677 4 25 theme CD8+ 553:556 arg1 clone 565:569 an HLA-E-restricted CD8+ T cell clone 533:569 an HLA-E-restricted CD8+ T cell clone isolated from an Mtb latently infected individual 533:619 In this manuscript, we identified the antigen recognized by an HLA-E-restricted CD8+ T cell clone isolated from an Mtb latently infected individual as a peptide from the Mtb protein, MPT32. 28676677 6 26 theme cell 952:955 arg1 response 964:971 an HLA-E specific CD8+ T cell immune response 927:971 an HLA-E specific CD8+ T cell immune response 927:971 This is the first description of a post-translationally modified Mtb-derived protein antigen presented in the context of an HLA-E specific CD8+ T cell immune response. 28676677 6 27 theme Mtb-derived 871:881 arg1 antigen 891:897 a post-translationally modified Mtb-derived protein antigen 839:897 a post-translationally modified Mtb-derived protein antigen presented in the context of an HLA-E specific CD8+ T cell immune response 839:971 This is the first description of a post-translationally modified Mtb-derived protein antigen presented in the context of an HLA-E specific CD8+ T cell immune response. 28676677 1 28 with Infection 102:110 arg1 tuberculosis 131:142 Mycobacterium tuberculosis 117:142 Mycobacterium tuberculosis (Mtb) 117:148 Infection with Mycobacterium tuberculosis (Mtb), the bacterium that causes tuberculosis, remains a global health concern. 28676677 1 28 with Infection 102:110 arg1 bacterium 155:163 the bacterium 151:163 the bacterium that causes tuberculosis 151:188 Infection with Mycobacterium tuberculosis (Mtb), the bacterium that causes tuberculosis, remains a global health concern. 28676677 1 28 with Infection 102:110 arg1 Mtb 145:147 Mtb 145:147 Mtb 145:147 Infection with Mycobacterium tuberculosis (Mtb), the bacterium that causes tuberculosis, remains a global health concern. 28676677 4 29 theme HLA-E-restricted 536:551 arg1 clone 565:569 an HLA-E-restricted CD8+ T cell clone 533:569 an HLA-E-restricted CD8+ T cell clone isolated from an Mtb latently infected individual 533:619 In this manuscript, we identified the antigen recognized by an HLA-E-restricted CD8+ T cell clone isolated from an Mtb latently infected individual as a peptide from the Mtb protein, MPT32. 28676677 3 30 link pathogen-derived 430:445 arg1 peptides 447:454 pathogen-derived peptides 430:454 pathogen-derived peptides 430:454 We and others have demonstrated that the non-classical MHC I molecule HLA-E can present pathogen-derived peptides to CD8+ T cells. 28676677 7 31 theme mycobacterial 1037:1049 arg1 modification 1051:1062 a unique mycobacterial modification 1028:1062 a unique mycobacterial modification 1028:1062 The identification of an immune response that targets a unique mycobacterial modification is novel and may have practical impact in the development of vaccines and diagnostics. 28676677 4 32 theme Mtb 643:645 arg1 MPT32 656:660 MPT32 656:660 MPT32 656:660 In this manuscript, we identified the antigen recognized by an HLA-E-restricted CD8+ T cell clone isolated from an Mtb latently infected individual as a peptide from the Mtb protein, MPT32. 28676677 4 32 theme Mtb 643:645 arg1 protein 647:653 the Mtb protein 639:653 the Mtb protein 639:653 In this manuscript, we identified the antigen recognized by an HLA-E-restricted CD8+ T cell clone isolated from an Mtb latently infected individual as a peptide from the Mtb protein, MPT32. 28676677 5 33 theme Rv1002c 792:798 arg1 gene 800:803 the Rv1002c gene 788:803 the Rv1002c gene 788:803 Recognition by the CD8+ T cell clone required N-terminal O-linked mannosylation of MPT32 by a mannosyltransferase encoded by the Rv1002c gene. 28676677 6 34 theme T 950:950 arg1 response 964:971 an HLA-E specific CD8+ T cell immune response 927:971 an HLA-E specific CD8+ T cell immune response 927:971 This is the first description of a post-translationally modified Mtb-derived protein antigen presented in the context of an HLA-E specific CD8+ T cell immune response. 28676677 5 35 link O-linked 720:727 arg1 mannosylation 729:741 N-terminal O-linked mannosylation 709:741 N-terminal O-linked mannosylation of MPT32 by a mannosyltransferase encoded by the Rv1002c gene 709:803 Recognition by the CD8+ T cell clone required N-terminal O-linked mannosylation of MPT32 by a mannosyltransferase encoded by the Rv1002c gene. 28676677 3 36 theme CD8+ 459:462 arg1 cells 466:470 CD8+ T cells 459:470 CD8+ T cells 459:470 We and others have demonstrated that the non-classical MHC I molecule HLA-E can present pathogen-derived peptides to CD8+ T cells. 28676677 4 37 theme T 558:558 arg1 clone 565:569 an HLA-E-restricted CD8+ T cell clone 533:569 an HLA-E-restricted CD8+ T cell clone isolated from an Mtb latently infected individual 533:619 In this manuscript, we identified the antigen recognized by an HLA-E-restricted CD8+ T cell clone isolated from an Mtb latently infected individual as a peptide from the Mtb protein, MPT32. 28676677 3 38 theme T 464:464 arg1 cells 466:470 CD8+ T cells 459:470 CD8+ T cells 459:470 We and others have demonstrated that the non-classical MHC I molecule HLA-E can present pathogen-derived peptides to CD8+ T cells. 28676677 0 39 theme Mycobacterium 38:50 arg1 MPT32 73:77 the Mycobacterium tuberculosis Protein MPT32 34:77 the Mycobacterium tuberculosis Protein MPT32 to Human CD8+ T cells 34:99 HLA-E Presents Glycopeptides from the Mycobacterium tuberculosis Protein MPT32 to Human CD8+ T cells. 28676677 2 40 theme Mtb 327:329 arg1 infection 331:339 Mtb infection 327:339 Mtb infection 327:339 Both classically and non-classically restricted cytotoxic CD8+ T cells are important to the control of Mtb infection. 28676677 5 41 theme CD8+ 682:685 arg1 clone 694:698 the CD8+ T cell clone 678:698 the CD8+ T cell clone 678:698 Recognition by the CD8+ T cell clone required N-terminal O-linked mannosylation of MPT32 by a mannosyltransferase encoded by the Rv1002c gene. 28676677 6 42 theme specific 936:943 arg1 response 964:971 an HLA-E specific CD8+ T cell immune response 927:971 an HLA-E specific CD8+ T cell immune response 927:971 This is the first description of a post-translationally modified Mtb-derived protein antigen presented in the context of an HLA-E specific CD8+ T cell immune response. 28676677 6 43 theme HLA-E 930:934 arg1 response 964:971 an HLA-E specific CD8+ T cell immune response 927:971 an HLA-E specific CD8+ T cell immune response 927:971 This is the first description of a post-translationally modified Mtb-derived protein antigen presented in the context of an HLA-E specific CD8+ T cell immune response. 28676677 5 44 theme T 687:687 arg1 clone 694:698 the CD8+ T cell clone 678:698 the CD8+ T cell clone 678:698 Recognition by the CD8+ T cell clone required N-terminal O-linked mannosylation of MPT32 by a mannosyltransferase encoded by the Rv1002c gene. 28676677 7 45 theme diagnostics 1138:1148 arg1 development 1110:1120 the development 1106:1120 the development of vaccines and diagnostics 1106:1148 The identification of an immune response that targets a unique mycobacterial modification is novel and may have practical impact in the development of vaccines and diagnostics. 28676677 1 46 theme global 201:206 arg1 concern 215:221 a global health concern 199:221 a global health concern 199:221 Infection with Mycobacterium tuberculosis (Mtb), the bacterium that causes tuberculosis, remains a global health concern. 28676677 0 47 theme Protein 65:71 arg1 MPT32 73:77 the Mycobacterium tuberculosis Protein MPT32 34:77 the Mycobacterium tuberculosis Protein MPT32 to Human CD8+ T cells 34:99 HLA-E Presents Glycopeptides from the Mycobacterium tuberculosis Protein MPT32 to Human CD8+ T cells. 28676677 0 48 from MPT32 73:77 arg1 Glycopeptides 15:27 Glycopeptides 15:27 Glycopeptides from the Mycobacterium tuberculosis Protein MPT32 to Human CD8+ T cells 15:99 HLA-E Presents Glycopeptides from the Mycobacterium tuberculosis Protein MPT32 to Human CD8+ T cells. 28676677 7 49 theme immune 999:1004 arg1 response 1006:1013 an immune response 996:1013 an immune response that targets a unique mycobacterial modification 996:1062 The identification of an immune response that targets a unique mycobacterial modification is novel and may have practical impact in the development of vaccines and diagnostics. 28676677 2 50 theme infection 331:339 arg1 control 316:322 the control 312:322 the control of Mtb infection 312:339 Both classically and non-classically restricted cytotoxic CD8+ T cells are important to the control of Mtb infection. 28676677 3 51 theme MHC 397:399 arg1 molecule 403:410 the non-classical MHC I molecule 379:410 the non-classical MHC I molecule HLA-E 379:416 We and others have demonstrated that the non-classical MHC I molecule HLA-E can present pathogen-derived peptides to CD8+ T cells. 28676677 1 52 theme Mycobacterium 117:129 arg1 tuberculosis 131:142 Mycobacterium tuberculosis 117:142 Mycobacterium tuberculosis (Mtb) 117:148 Infection with Mycobacterium tuberculosis (Mtb), the bacterium that causes tuberculosis, remains a global health concern. 28676677 1 52 theme Mycobacterium 117:129 arg1 bacterium 155:163 the bacterium 151:163 the bacterium that causes tuberculosis 151:188 Infection with Mycobacterium tuberculosis (Mtb), the bacterium that causes tuberculosis, remains a global health concern. 28676677 1 52 theme Mycobacterium 117:129 arg1 Mtb 145:147 Mtb 145:147 Mtb 145:147 Infection with Mycobacterium tuberculosis (Mtb), the bacterium that causes tuberculosis, remains a global health concern. 28676677 7 53 theme response 1006:1013 arg1 novel 1067:1071 novel 1067:1071 novel 1067:1071 The identification of an immune response that targets a unique mycobacterial modification is novel and may have practical impact in the development of vaccines and diagnostics. 28676677 7 53 theme response 1006:1013 arg1 identification 978:991 The identification 974:991 The identification of an immune response that targets a unique mycobacterial modification 974:1062 The identification of an immune response that targets a unique mycobacterial modification is novel and may have practical impact in the development of vaccines and diagnostics. 28676677 2 54 theme restricted 261:270 arg1 cells 289:293 Both classically and non-classically restricted cytotoxic CD8+ T cells 224:293 Both classically and non-classically restricted cytotoxic CD8+ T cells 224:293 Both classically and non-classically restricted cytotoxic CD8+ T cells are important to the control of Mtb infection. 28676677 1 55 theme health 208:213 arg1 concern 215:221 a global health concern 199:221 a global health concern 199:221 Infection with Mycobacterium tuberculosis (Mtb), the bacterium that causes tuberculosis, remains a global health concern. 28676677 7 56 contain have 1081:1084 arg2 impact 1096:1101 practical impact 1086:1101 practical impact 1086:1101 The identification of an immune response that targets a unique mycobacterial modification is novel and may have practical impact in the development of vaccines and diagnostics. 28676677 7 56 contain have 1081:1084 arg1 novel 1067:1071 novel 1067:1071 novel 1067:1071 The identification of an immune response that targets a unique mycobacterial modification is novel and may have practical impact in the development of vaccines and diagnostics. 28676677 7 56 contain have 1081:1084 arg1 identification 978:991 The identification 974:991 The identification of an immune response that targets a unique mycobacterial modification 974:1062 The identification of an immune response that targets a unique mycobacterial modification is novel and may have practical impact in the development of vaccines and diagnostics. 28676677 5 57 theme O-linked 720:727 arg1 mannosylation 729:741 N-terminal O-linked mannosylation 709:741 N-terminal O-linked mannosylation of MPT32 by a mannosyltransferase encoded by the Rv1002c gene 709:803 Recognition by the CD8+ T cell clone required N-terminal O-linked mannosylation of MPT32 by a mannosyltransferase encoded by the Rv1002c gene. 28676677 6 58 link Mtb-derived 871:881 arg1 antigen 891:897 a post-translationally modified Mtb-derived protein antigen 839:897 a post-translationally modified Mtb-derived protein antigen presented in the context of an HLA-E specific CD8+ T cell immune response 839:971 This is the first description of a post-translationally modified Mtb-derived protein antigen presented in the context of an HLA-E specific CD8+ T cell immune response. 28676677 4 59 attach isolated 571:578 arg1 individual 610:619 an Mtb latently infected individual 585:619 an Mtb latently infected individual 585:619 In this manuscript, we identified the antigen recognized by an HLA-E-restricted CD8+ T cell clone isolated from an Mtb latently infected individual as a peptide from the Mtb protein, MPT32. 28676677 4 59 attach isolated 571:578 arg2 clone 565:569 an HLA-E-restricted CD8+ T cell clone 533:569 an HLA-E-restricted CD8+ T cell clone isolated from an Mtb latently infected individual 533:619 In this manuscript, we identified the antigen recognized by an HLA-E-restricted CD8+ T cell clone isolated from an Mtb latently infected individual as a peptide from the Mtb protein, MPT32. 28676677 4 60 theme infected 601:608 arg1 individual 610:619 an Mtb latently infected individual 585:619 an Mtb latently infected individual 585:619 In this manuscript, we identified the antigen recognized by an HLA-E-restricted CD8+ T cell clone isolated from an Mtb latently infected individual as a peptide from the Mtb protein, MPT32. 28676677 3 61 theme non-classical 383:395 arg1 molecule 403:410 the non-classical MHC I molecule 379:410 the non-classical MHC I molecule HLA-E 379:416 We and others have demonstrated that the non-classical MHC I molecule HLA-E can present pathogen-derived peptides to CD8+ T cells. 28676677 7 62 theme unique 1030:1035 arg1 modification 1051:1062 a unique mycobacterial modification 1028:1062 a unique mycobacterial modification 1028:1062 The identification of an immune response that targets a unique mycobacterial modification is novel and may have practical impact in the development of vaccines and diagnostics. 28676677 4 63 theme Mtb 588:590 arg1 individual 610:619 an Mtb latently infected individual 585:619 an Mtb latently infected individual 585:619 In this manuscript, we identified the antigen recognized by an HLA-E-restricted CD8+ T cell clone isolated from an Mtb latently infected individual as a peptide from the Mtb protein, MPT32. 28637651 5 0 theme cold 783:786 arg1 intolerance 788:798 severe cold intolerance 776:798 severe cold intolerance with decreased uncoupling protein 1 (Ucp1) expression 776:852 Deletion of Ogt in WAT and BAT using adiponectin promoter-driven Cre recombinase resulted in severe cold intolerance with decreased uncoupling protein 1 (Ucp1) expression. 28637651 6 1 theme 1-α 1018:1020 arg1 expression 1030:1039 decreased peroxisome proliferator-activated receptor γ coactivator 1-α protein expression 951:1039 decreased peroxisome proliferator-activated receptor γ coactivator 1-α protein expression 951:1039 Furthermore, Ogt deletion led to decreased mitochondrial protein expression in conjunction with decreased peroxisome proliferator-activated receptor γ coactivator 1-α protein expression. 28637651 10 2 theme cold-induced 1559:1570 arg1 thermogenesis 1572:1584 cold-induced thermogenesis 1559:1584 cold-induced thermogenesis 1559:1584 In conclusion, O-GlcNAc modification is essential for cold-induced thermogenesis and mitochondrial biogenesis in BAT. 28637651 3 3 from role 543:546 arg1 tissues 584:590 adipose tissues 576:590 adipose tissues 576:590 However, little is known about the role of O-GlcNAc modification in adipose tissues. 28637651 0 4 theme Adipose 77:83 arg1 Tissue 85:90 Brown Adipose Tissue 71:90 Brown Adipose Tissue Through Mitochondrial Biogenesis 71:123 Pivotal Role of O-GlcNAc Modification in Cold-Induced Thermogenesis by Brown Adipose Tissue Through Mitochondrial Biogenesis. 28637651 0 5 from Role 8:11 arg1 Thermogenesis 54:66 Cold-Induced Thermogenesis 41:66 Cold-Induced Thermogenesis by Brown Adipose Tissue Through Mitochondrial Biogenesis 41:123 Pivotal Role of O-GlcNAc Modification in Cold-Induced Thermogenesis by Brown Adipose Tissue Through Mitochondrial Biogenesis. 28637651 7 6 theme Ucp1 1111:1114 arg1 recombinase 1136:1146 Ucp1 promoter-driven Cre recombinase 1111:1146 Ucp1 promoter-driven Cre recombinase 1111:1146 This phenotype was further confirmed by deletion of Ogt in BAT using Ucp1 promoter-driven Cre recombinase, suggesting that O-GlcNAc modification in BAT is responsible for cold-induced thermogenesis. 28637651 1 7 theme significant 245:255 arg1 roles 257:261 significant roles 245:261 significant roles 245:261 Adipose tissues considerably influence metabolic homeostasis, and both white (WAT) and brown (BAT) adipose tissue play significant roles in lipid and glucose metabolism. 28637651 0 8 theme Mitochondrial 100:112 arg1 Biogenesis 114:123 Mitochondrial Biogenesis 100:123 Mitochondrial Biogenesis 100:123 Pivotal Role of O-GlcNAc Modification in Cold-Induced Thermogenesis by Brown Adipose Tissue Through Mitochondrial Biogenesis. 28637651 9 9 theme fatty 1382:1386 arg1 diet 1408:1411 a fatty acid-rich ketogenic diet 1380:1411 a fatty acid-rich ketogenic diet lacking carbohydrates 1380:1433 This effect was mitigated after normal diet consumption but not after consumption of a fatty acid-rich ketogenic diet lacking carbohydrates, suggesting impaired diet-induced thermogenesis, particularly by fat. 28637651 7 10 theme O-GlcNAc 1165:1172 arg1 modification 1174:1185 O-GlcNAc modification 1165:1185 O-GlcNAc modification in BAT 1165:1192 This phenotype was further confirmed by deletion of Ogt in BAT using Ucp1 promoter-driven Cre recombinase, suggesting that O-GlcNAc modification in BAT is responsible for cold-induced thermogenesis. 28637651 5 11 theme Cre 748:750 arg1 recombinase 752:762 adiponectin promoter-driven Cre recombinase 720:762 adiponectin promoter-driven Cre recombinase 720:762 Deletion of Ogt in WAT and BAT using adiponectin promoter-driven Cre recombinase resulted in severe cold intolerance with decreased uncoupling protein 1 (Ucp1) expression. 28637651 9 12 theme acid-rich 1388:1396 arg1 diet 1408:1411 a fatty acid-rich ketogenic diet 1380:1411 a fatty acid-rich ketogenic diet lacking carbohydrates 1380:1433 This effect was mitigated after normal diet consumption but not after consumption of a fatty acid-rich ketogenic diet lacking carbohydrates, suggesting impaired diet-induced thermogenesis, particularly by fat. 28637651 10 13 from thermogenesis 1572:1584 arg1 BAT 1618:1620 BAT 1618:1620 BAT 1618:1620 In conclusion, O-GlcNAc modification is essential for cold-induced thermogenesis and mitochondrial biogenesis in BAT. 28637651 3 14 theme O-GlcNAc 551:558 arg1 modification 560:571 O-GlcNAc modification 551:571 O-GlcNAc modification 551:571 However, little is known about the role of O-GlcNAc modification in adipose tissues. 28637651 10 15 from essential 1545:1553 arg1 conclusion 1508:1517 conclusion 1508:1517 conclusion 1508:1517 In conclusion, O-GlcNAc modification is essential for cold-induced thermogenesis and mitochondrial biogenesis in BAT. 28637651 6 16 from expression 920:929 arg1 conjunction 934:944 conjunction 934:944 conjunction with decreased peroxisome proliferator-activated receptor γ coactivator 1-α protein expression 934:1039 Furthermore, Ogt deletion led to decreased mitochondrial protein expression in conjunction with decreased peroxisome proliferator-activated receptor γ coactivator 1-α protein expression. 28637651 6 17 theme protein 912:918 arg1 expression 920:929 decreased mitochondrial protein expression 888:929 decreased mitochondrial protein expression in conjunction with decreased peroxisome proliferator-activated receptor γ coactivator 1-α protein expression 888:1039 Furthermore, Ogt deletion led to decreased mitochondrial protein expression in conjunction with decreased peroxisome proliferator-activated receptor γ coactivator 1-α protein expression. 28637651 2 18 theme various 408:414 arg1 proteins 416:423 various proteins 408:423 various proteins 408:423 O-linked N-acetylglucosamine (O-GlcNAc) modification is characterized by the addition of N-acetylglucosamine to various proteins by O-GlcNAc transferase (Ogt), subsequently modulating various cellular processes. 28637651 5 19 theme protein 826:832 arg1 expression 843:852 decreased uncoupling protein 1 (Ucp1) expression 805:852 decreased uncoupling protein 1 (Ucp1) expression 805:852 Deletion of Ogt in WAT and BAT using adiponectin promoter-driven Cre recombinase resulted in severe cold intolerance with decreased uncoupling protein 1 (Ucp1) expression. 28637651 6 20 theme mitochondrial 898:910 arg1 expression 920:929 decreased mitochondrial protein expression 888:929 decreased mitochondrial protein expression in conjunction with decreased peroxisome proliferator-activated receptor γ coactivator 1-α protein expression 888:1039 Furthermore, Ogt deletion led to decreased mitochondrial protein expression in conjunction with decreased peroxisome proliferator-activated receptor γ coactivator 1-α protein expression. 28637651 10 21 theme mitochondrial 1590:1602 arg1 biogenesis 1604:1613 mitochondrial biogenesis 1590:1613 mitochondrial biogenesis 1590:1613 In conclusion, O-GlcNAc modification is essential for cold-induced thermogenesis and mitochondrial biogenesis in BAT. 28637651 7 22 theme Cre 1132:1134 arg1 recombinase 1136:1146 Ucp1 promoter-driven Cre recombinase 1111:1146 Ucp1 promoter-driven Cre recombinase 1111:1146 This phenotype was further confirmed by deletion of Ogt in BAT using Ucp1 promoter-driven Cre recombinase, suggesting that O-GlcNAc modification in BAT is responsible for cold-induced thermogenesis. 28637651 10 23 from biogenesis 1604:1613 arg1 BAT 1618:1620 BAT 1618:1620 BAT 1618:1620 In conclusion, O-GlcNAc modification is essential for cold-induced thermogenesis and mitochondrial biogenesis in BAT. 28637651 4 24 theme cold-induced 655:666 arg1 thermogenesis 668:680 cold-induced thermogenesis 655:680 cold-induced thermogenesis 655:680 Here, we report the critical role of O-GlcNAc modification in cold-induced thermogenesis. 28637651 6 25 theme decreased 888:896 arg1 expression 920:929 decreased mitochondrial protein expression 888:929 decreased mitochondrial protein expression in conjunction with decreased peroxisome proliferator-activated receptor γ coactivator 1-α protein expression 888:1039 Furthermore, Ogt deletion led to decreased mitochondrial protein expression in conjunction with decreased peroxisome proliferator-activated receptor γ coactivator 1-α protein expression. 28637651 4 26 from role 622:625 arg1 thermogenesis 668:680 cold-induced thermogenesis 655:680 cold-induced thermogenesis 655:680 Here, we report the critical role of O-GlcNAc modification in cold-induced thermogenesis. 28637651 3 27 theme adipose 576:582 arg1 tissues 584:590 adipose tissues 576:590 adipose tissues 576:590 However, little is known about the role of O-GlcNAc modification in adipose tissues. 28637651 9 28 theme ketogenic 1398:1406 arg1 diet 1408:1411 a fatty acid-rich ketogenic diet 1380:1411 a fatty acid-rich ketogenic diet lacking carbohydrates 1380:1433 This effect was mitigated after normal diet consumption but not after consumption of a fatty acid-rich ketogenic diet lacking carbohydrates, suggesting impaired diet-induced thermogenesis, particularly by fat. 28637651 2 29 theme N-acetylglucosamine 385:403 arg1 addition 373:380 the addition 369:380 the addition of N-acetylglucosamine to various proteins 369:423 O-linked N-acetylglucosamine (O-GlcNAc) modification is characterized by the addition of N-acetylglucosamine to various proteins by O-GlcNAc transferase (Ogt), subsequently modulating various cellular processes. 28637651 0 30 theme Pivotal 0:6 arg1 Role 8:11 Pivotal Role 0:11 Pivotal Role of O-GlcNAc Modification in Cold-Induced Thermogenesis by Brown Adipose Tissue Through Mitochondrial Biogenesis. 0:124 Pivotal Role of O-GlcNAc Modification in Cold-Induced Thermogenesis by Brown Adipose Tissue Through Mitochondrial Biogenesis. 28637651 1 31 theme lipid 266:270 arg1 metabolism 284:293 lipid and glucose metabolism 266:293 metabolism 284:293 Adipose tissues considerably influence metabolic homeostasis, and both white (WAT) and brown (BAT) adipose tissue play significant roles in lipid and glucose metabolism. 28637651 7 32 from modification 1174:1185 arg1 BAT 1190:1192 BAT 1190:1192 BAT 1190:1192 This phenotype was further confirmed by deletion of Ogt in BAT using Ucp1 promoter-driven Cre recombinase, suggesting that O-GlcNAc modification in BAT is responsible for cold-induced thermogenesis. 28637651 2 33 theme N-acetylglucosamine 305:323 arg1 modification 336:347 O-linked N-acetylglucosamine (O-GlcNAc) modification 296:347 O-linked N-acetylglucosamine (O-GlcNAc) modification 296:347 O-linked N-acetylglucosamine (O-GlcNAc) modification is characterized by the addition of N-acetylglucosamine to various proteins by O-GlcNAc transferase (Ogt), subsequently modulating various cellular processes. 28637651 0 34 theme O-GlcNAc 16:23 arg1 Modification 25:36 O-GlcNAc Modification 16:36 O-GlcNAc Modification 16:36 Pivotal Role of O-GlcNAc Modification in Cold-Induced Thermogenesis by Brown Adipose Tissue Through Mitochondrial Biogenesis. 28637651 6 35 theme protein 1022:1028 arg1 expression 1030:1039 decreased peroxisome proliferator-activated receptor γ coactivator 1-α protein expression 951:1039 decreased peroxisome proliferator-activated receptor γ coactivator 1-α protein expression 951:1039 Furthermore, Ogt deletion led to decreased mitochondrial protein expression in conjunction with decreased peroxisome proliferator-activated receptor γ coactivator 1-α protein expression. 28637651 7 36 theme promoter-driven 1116:1130 arg1 recombinase 1136:1146 Ucp1 promoter-driven Cre recombinase 1111:1146 Ucp1 promoter-driven Cre recombinase 1111:1146 This phenotype was further confirmed by deletion of Ogt in BAT using Ucp1 promoter-driven Cre recombinase, suggesting that O-GlcNAc modification in BAT is responsible for cold-induced thermogenesis. 28637651 11 37 theme BAT 1673:1675 arg1 responses 1691:1699 BAT physiological responses 1673:1699 BAT physiological responses 1673:1699 Glucose flux into BAT may be a signal to maintain BAT physiological responses. 28637651 2 38 theme O-linked 296:303 arg1 O-GlcNAc 326:333 O-GlcNAc 326:333 O-GlcNAc 326:333 O-linked N-acetylglucosamine (O-GlcNAc) modification is characterized by the addition of N-acetylglucosamine to various proteins by O-GlcNAc transferase (Ogt), subsequently modulating various cellular processes. 28637651 2 38 theme O-linked 296:303 arg1 N-acetylglucosamine 305:323 O-linked N-acetylglucosamine 296:323 O-linked N-acetylglucosamine (O-GlcNAc) modification 296:347 O-linked N-acetylglucosamine (O-GlcNAc) modification is characterized by the addition of N-acetylglucosamine to various proteins by O-GlcNAc transferase (Ogt), subsequently modulating various cellular processes. 28637651 4 39 theme O-GlcNAc 630:637 arg1 modification 639:650 O-GlcNAc modification 630:650 O-GlcNAc modification 630:650 Here, we report the critical role of O-GlcNAc modification in cold-induced thermogenesis. 28637651 8 40 theme fasting 1275:1281 arg1 conditions 1283:1292 fasting conditions 1275:1292 fasting conditions 1275:1292 Hypothermia was significant under fasting conditions. 28637651 1 41 theme glucose 276:282 arg1 metabolism 284:293 lipid and glucose metabolism 266:293 metabolism 284:293 Adipose tissues considerably influence metabolic homeostasis, and both white (WAT) and brown (BAT) adipose tissue play significant roles in lipid and glucose metabolism. 28637651 5 42 theme BAT 710:712 arg1 Deletion 683:690 Deletion 683:690 Deletion of Ogt in WAT and BAT using adiponectin promoter-driven Cre recombinase 683:762 Deletion of Ogt in WAT and BAT using adiponectin promoter-driven Cre recombinase resulted in severe cold intolerance with decreased uncoupling protein 1 (Ucp1) expression. 28637651 9 43 theme diet 1334:1337 arg1 consumption 1339:1349 normal diet consumption 1327:1349 normal diet consumption 1327:1349 This effect was mitigated after normal diet consumption but not after consumption of a fatty acid-rich ketogenic diet lacking carbohydrates, suggesting impaired diet-induced thermogenesis, particularly by fat. 28637651 7 44 theme cold-induced 1213:1224 arg1 thermogenesis 1226:1238 cold-induced thermogenesis 1213:1238 cold-induced thermogenesis 1213:1238 This phenotype was further confirmed by deletion of Ogt in BAT using Ucp1 promoter-driven Cre recombinase, suggesting that O-GlcNAc modification in BAT is responsible for cold-induced thermogenesis. 28637651 2 45 theme O-GlcNAc 428:435 arg1 Ogt 450:452 Ogt 450:452 Ogt 450:452 O-linked N-acetylglucosamine (O-GlcNAc) modification is characterized by the addition of N-acetylglucosamine to various proteins by O-GlcNAc transferase (Ogt), subsequently modulating various cellular processes. 28637651 2 45 theme O-GlcNAc 428:435 arg1 transferase 437:447 O-GlcNAc transferase 428:447 O-GlcNAc transferase (Ogt) 428:453 O-linked N-acetylglucosamine (O-GlcNAc) modification is characterized by the addition of N-acetylglucosamine to various proteins by O-GlcNAc transferase (Ogt), subsequently modulating various cellular processes. 28637651 2 46 theme cellular 488:495 arg1 processes 497:505 various cellular processes 480:505 various cellular processes 480:505 O-linked N-acetylglucosamine (O-GlcNAc) modification is characterized by the addition of N-acetylglucosamine to various proteins by O-GlcNAc transferase (Ogt), subsequently modulating various cellular processes. 28637651 6 47 theme coactivator 1006:1016 arg1 expression 1030:1039 decreased peroxisome proliferator-activated receptor γ coactivator 1-α protein expression 951:1039 decreased peroxisome proliferator-activated receptor γ coactivator 1-α protein expression 951:1039 Furthermore, Ogt deletion led to decreased mitochondrial protein expression in conjunction with decreased peroxisome proliferator-activated receptor γ coactivator 1-α protein expression. 28637651 5 48 theme adiponectin 720:730 arg1 recombinase 752:762 adiponectin promoter-driven Cre recombinase 720:762 adiponectin promoter-driven Cre recombinase 720:762 Deletion of Ogt in WAT and BAT using adiponectin promoter-driven Cre recombinase resulted in severe cold intolerance with decreased uncoupling protein 1 (Ucp1) expression. 28637651 1 49 theme brown 213:217 arg1 BAT 220:222 BAT 220:222 BAT 220:222 Adipose tissues considerably influence metabolic homeostasis, and both white (WAT) and brown (BAT) adipose tissue play significant roles in lipid and glucose metabolism. 28637651 1 49 theme brown 213:217 arg1 tissue 233:238 white (WAT) and brown (BAT) adipose tissue 197:238 tissue 233:238 Adipose tissues considerably influence metabolic homeostasis, and both white (WAT) and brown (BAT) adipose tissue play significant roles in lipid and glucose metabolism. 28637651 2 50 theme various 480:486 arg1 processes 497:505 various cellular processes 480:505 various cellular processes 480:505 O-linked N-acetylglucosamine (O-GlcNAc) modification is characterized by the addition of N-acetylglucosamine to various proteins by O-GlcNAc transferase (Ogt), subsequently modulating various cellular processes. 28637651 2 51 link O-linked 296:303 arg1 O-GlcNAc 326:333 O-GlcNAc 326:333 O-GlcNAc 326:333 O-linked N-acetylglucosamine (O-GlcNAc) modification is characterized by the addition of N-acetylglucosamine to various proteins by O-GlcNAc transferase (Ogt), subsequently modulating various cellular processes. 28637651 2 51 link O-linked 296:303 arg1 N-acetylglucosamine 305:323 O-linked N-acetylglucosamine 296:323 O-linked N-acetylglucosamine (O-GlcNAc) modification 296:347 O-linked N-acetylglucosamine (O-GlcNAc) modification is characterized by the addition of N-acetylglucosamine to various proteins by O-GlcNAc transferase (Ogt), subsequently modulating various cellular processes. 28637651 0 52 theme Modification 25:36 arg1 Role 8:11 Pivotal Role 0:11 Pivotal Role of O-GlcNAc Modification in Cold-Induced Thermogenesis by Brown Adipose Tissue Through Mitochondrial Biogenesis. 0:124 Pivotal Role of O-GlcNAc Modification in Cold-Induced Thermogenesis by Brown Adipose Tissue Through Mitochondrial Biogenesis. 28637651 6 53 with conjunction 934:944 arg1 expression 1030:1039 decreased peroxisome proliferator-activated receptor γ coactivator 1-α protein expression 951:1039 decreased peroxisome proliferator-activated receptor γ coactivator 1-α protein expression 951:1039 Furthermore, Ogt deletion led to decreased mitochondrial protein expression in conjunction with decreased peroxisome proliferator-activated receptor γ coactivator 1-α protein expression. 28637651 4 54 theme modification 639:650 arg1 role 622:625 the critical role 609:625 the critical role of O-GlcNAc modification in cold-induced thermogenesis 609:680 Here, we report the critical role of O-GlcNAc modification in cold-induced thermogenesis. 28637651 5 55 theme uncoupling 815:824 arg1 protein 826:832 uncoupling protein 1 815:834 decreased uncoupling protein 1 (Ucp1) expression 805:852 Deletion of Ogt in WAT and BAT using adiponectin promoter-driven Cre recombinase resulted in severe cold intolerance with decreased uncoupling protein 1 (Ucp1) expression. 28637651 5 55 theme uncoupling 815:824 arg1 Ucp1 837:840 Ucp1 837:840 Ucp1 837:840 Deletion of Ogt in WAT and BAT using adiponectin promoter-driven Cre recombinase resulted in severe cold intolerance with decreased uncoupling protein 1 (Ucp1) expression. 28637651 5 56 theme promoter-driven 732:746 arg1 recombinase 752:762 adiponectin promoter-driven Cre recombinase 720:762 adiponectin promoter-driven Cre recombinase 720:762 Deletion of Ogt in WAT and BAT using adiponectin promoter-driven Cre recombinase resulted in severe cold intolerance with decreased uncoupling protein 1 (Ucp1) expression. 28637651 6 57 theme Ogt 868:870 arg1 deletion 872:879 Ogt deletion 868:879 Ogt deletion 868:879 Furthermore, Ogt deletion led to decreased mitochondrial protein expression in conjunction with decreased peroxisome proliferator-activated receptor γ coactivator 1-α protein expression. 28637651 10 58 theme O-GlcNAc 1520:1527 arg1 modification 1529:1540 O-GlcNAc modification 1520:1540 O-GlcNAc modification 1520:1540 In conclusion, O-GlcNAc modification is essential for cold-induced thermogenesis and mitochondrial biogenesis in BAT. 28637651 9 59 theme diet 1408:1411 arg1 consumption 1365:1375 consumption 1365:1375 consumption of a fatty acid-rich ketogenic diet lacking carbohydrates 1365:1433 This effect was mitigated after normal diet consumption but not after consumption of a fatty acid-rich ketogenic diet lacking carbohydrates, suggesting impaired diet-induced thermogenesis, particularly by fat. 28637651 1 60 theme Adipose 126:132 arg1 tissues 134:140 Adipose tissues 126:140 Adipose tissues 126:140 Adipose tissues considerably influence metabolic homeostasis, and both white (WAT) and brown (BAT) adipose tissue play significant roles in lipid and glucose metabolism. 28637651 0 61 theme Cold-Induced 41:52 arg1 Thermogenesis 54:66 Cold-Induced Thermogenesis 41:66 Cold-Induced Thermogenesis by Brown Adipose Tissue Through Mitochondrial Biogenesis 41:123 Pivotal Role of O-GlcNAc Modification in Cold-Induced Thermogenesis by Brown Adipose Tissue Through Mitochondrial Biogenesis. 28637651 6 62 theme proliferator-activated 972:993 arg1 receptor 995:1002 peroxisome proliferator-activated receptor 961:1002 decreased peroxisome proliferator-activated receptor γ coactivator 1-α protein expression 951:1039 Furthermore, Ogt deletion led to decreased mitochondrial protein expression in conjunction with decreased peroxisome proliferator-activated receptor γ coactivator 1-α protein expression. 28637651 5 63 theme Ogt 695:697 arg1 Deletion 683:690 Deletion 683:690 Deletion of Ogt in WAT and BAT using adiponectin promoter-driven Cre recombinase 683:762 Deletion of Ogt in WAT and BAT using adiponectin promoter-driven Cre recombinase resulted in severe cold intolerance with decreased uncoupling protein 1 (Ucp1) expression. 28637651 1 64 dep white 197:201 arg1 WAT 204:206 WAT 204:206 WAT 204:206 Adipose tissues considerably influence metabolic homeostasis, and both white (WAT) and brown (BAT) adipose tissue play significant roles in lipid and glucose metabolism. 28637651 9 65 theme normal 1327:1332 arg1 consumption 1339:1349 normal diet consumption 1327:1349 normal diet consumption 1327:1349 This effect was mitigated after normal diet consumption but not after consumption of a fatty acid-rich ketogenic diet lacking carbohydrates, suggesting impaired diet-induced thermogenesis, particularly by fat. 28637651 6 66 theme peroxisome 961:970 arg1 receptor 995:1002 peroxisome proliferator-activated receptor 961:1002 decreased peroxisome proliferator-activated receptor γ coactivator 1-α protein expression 951:1039 Furthermore, Ogt deletion led to decreased mitochondrial protein expression in conjunction with decreased peroxisome proliferator-activated receptor γ coactivator 1-α protein expression. 28637651 6 67 theme γ 1004:1004 arg1 expression 1030:1039 decreased peroxisome proliferator-activated receptor γ coactivator 1-α protein expression 951:1039 decreased peroxisome proliferator-activated receptor γ coactivator 1-α protein expression 951:1039 Furthermore, Ogt deletion led to decreased mitochondrial protein expression in conjunction with decreased peroxisome proliferator-activated receptor γ coactivator 1-α protein expression. 28637651 11 68 theme physiological 1677:1689 arg1 responses 1691:1699 BAT physiological responses 1673:1699 BAT physiological responses 1673:1699 Glucose flux into BAT may be a signal to maintain BAT physiological responses. 28637651 9 69 theme impaired 1447:1454 arg1 thermogenesis 1469:1481 impaired diet-induced thermogenesis 1447:1481 impaired diet-induced thermogenesis 1447:1481 This effect was mitigated after normal diet consumption but not after consumption of a fatty acid-rich ketogenic diet lacking carbohydrates, suggesting impaired diet-induced thermogenesis, particularly by fat. 28637651 3 70 theme modification 560:571 arg1 role 543:546 the role 539:546 the role of O-GlcNAc modification in adipose tissues 539:590 However, little is known about the role of O-GlcNAc modification in adipose tissues. 28637651 7 71 theme Ogt 1094:1096 arg1 deletion 1082:1089 deletion 1082:1089 deletion of Ogt 1082:1096 This phenotype was further confirmed by deletion of Ogt in BAT using Ucp1 promoter-driven Cre recombinase, suggesting that O-GlcNAc modification in BAT is responsible for cold-induced thermogenesis. 28637651 5 72 with intolerance 788:798 arg1 expression 843:852 decreased uncoupling protein 1 (Ucp1) expression 805:852 decreased uncoupling protein 1 (Ucp1) expression 805:852 Deletion of Ogt in WAT and BAT using adiponectin promoter-driven Cre recombinase resulted in severe cold intolerance with decreased uncoupling protein 1 (Ucp1) expression. 28637651 9 73 theme diet-induced 1456:1467 arg1 thermogenesis 1469:1481 impaired diet-induced thermogenesis 1447:1481 impaired diet-induced thermogenesis 1447:1481 This effect was mitigated after normal diet consumption but not after consumption of a fatty acid-rich ketogenic diet lacking carbohydrates, suggesting impaired diet-induced thermogenesis, particularly by fat. 28637651 0 74 theme Brown 71:75 arg1 Tissue 85:90 Brown Adipose Tissue 71:90 Brown Adipose Tissue Through Mitochondrial Biogenesis 71:123 Pivotal Role of O-GlcNAc Modification in Cold-Induced Thermogenesis by Brown Adipose Tissue Through Mitochondrial Biogenesis. 28637651 1 75 theme metabolic 165:173 arg1 homeostasis 175:185 metabolic homeostasis 165:185 metabolic homeostasis 165:185 Adipose tissues considerably influence metabolic homeostasis, and both white (WAT) and brown (BAT) adipose tissue play significant roles in lipid and glucose metabolism. 28637651 11 76 theme Glucose 1623:1629 arg1 signal 1654:1659 a signal 1652:1659 a signal to maintain BAT physiological responses 1652:1699 Glucose flux into BAT may be a signal to maintain BAT physiological responses. 28637651 11 76 theme Glucose 1623:1629 arg1 flux 1631:1634 Glucose flux 1623:1634 Glucose flux into BAT 1623:1643 Glucose flux into BAT may be a signal to maintain BAT physiological responses. 28637651 1 77 theme adipose 225:231 arg1 BAT 220:222 BAT 220:222 BAT 220:222 Adipose tissues considerably influence metabolic homeostasis, and both white (WAT) and brown (BAT) adipose tissue play significant roles in lipid and glucose metabolism. 28637651 1 77 theme adipose 225:231 arg1 tissue 233:238 white (WAT) and brown (BAT) adipose tissue 197:238 tissue 233:238 Adipose tissues considerably influence metabolic homeostasis, and both white (WAT) and brown (BAT) adipose tissue play significant roles in lipid and glucose metabolism. 28637651 5 78 theme severe 776:781 arg1 intolerance 788:798 severe cold intolerance 776:798 severe cold intolerance with decreased uncoupling protein 1 (Ucp1) expression 776:852 Deletion of Ogt in WAT and BAT using adiponectin promoter-driven Cre recombinase resulted in severe cold intolerance with decreased uncoupling protein 1 (Ucp1) expression. 28637651 6 79 theme decreased 951:959 arg1 expression 1030:1039 decreased peroxisome proliferator-activated receptor γ coactivator 1-α protein expression 951:1039 decreased peroxisome proliferator-activated receptor γ coactivator 1-α protein expression 951:1039 Furthermore, Ogt deletion led to decreased mitochondrial protein expression in conjunction with decreased peroxisome proliferator-activated receptor γ coactivator 1-α protein expression. 28637651 5 80 theme decreased 805:813 arg1 expression 843:852 decreased uncoupling protein 1 (Ucp1) expression 805:852 decreased uncoupling protein 1 (Ucp1) expression 805:852 Deletion of Ogt in WAT and BAT using adiponectin promoter-driven Cre recombinase resulted in severe cold intolerance with decreased uncoupling protein 1 (Ucp1) expression. 28637651 10 81 from conclusion 1508:1517 arg1 essential 1545:1553 essential 1545:1553 essential 1545:1553 In conclusion, O-GlcNAc modification is essential for cold-induced thermogenesis and mitochondrial biogenesis in BAT. 28637651 6 82 theme receptor 995:1002 arg1 expression 1030:1039 decreased peroxisome proliferator-activated receptor γ coactivator 1-α protein expression 951:1039 decreased peroxisome proliferator-activated receptor γ coactivator 1-α protein expression 951:1039 Furthermore, Ogt deletion led to decreased mitochondrial protein expression in conjunction with decreased peroxisome proliferator-activated receptor γ coactivator 1-α protein expression. 28637651 4 83 theme critical 613:620 arg1 role 622:625 the critical role 609:625 the critical role of O-GlcNAc modification in cold-induced thermogenesis 609:680 Here, we report the critical role of O-GlcNAc modification in cold-induced thermogenesis. 27111141 6 0 theme O-GlcNAc 977:984 arg1 transferase 986:996 O-GlcNAc transferase 977:996 O-GlcNAc transferase 977:996 Loss of O-GlcNAc transferase blocked T cell progenitor renewal, malignant transformation and peripheral T cell clonal expansion. 27111141 1 1 theme activated 158:166 arg1 lymphocytes 170:180 activated T lymphocytes 158:180 activated T lymphocytes 158:180 Sustained glucose and glutamine transport are essential for activated T lymphocytes to support ATP and macromolecule biosynthesis. 27111141 4 2 theme intracellular 651:663 arg1 O-GlcNAcylation 673:687 increased intracellular protein O-GlcNAcylation 641:687 increased intracellular protein O-GlcNAcylation 641:687 Immune-activated T cells contained higher concentrations of UDP-GlcNAc and increased intracellular protein O-GlcNAcylation controlled by the enzyme O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosyltransferase as compared with naive cells. 27111141 5 3 theme key 868:870 arg1 Notch 820:824 Notch 820:824 Notch 820:824 We identified Notch, the T cell antigen receptor and c-Myc as key controllers of T cell protein O-GlcNAcylation via regulation of glucose and glutamine transport. 27111141 5 3 theme key 868:870 arg1 controllers 872:882 key controllers 868:882 key controllers of T cell protein O-GlcNAcylation 868:916 We identified Notch, the T cell antigen receptor and c-Myc as key controllers of T cell protein O-GlcNAcylation via regulation of glucose and glutamine transport. 27111141 4 4 theme Immune-activated 566:581 arg1 cells 585:589 Immune-activated T cells 566:589 Immune-activated T cells 566:589 Immune-activated T cells contained higher concentrations of UDP-GlcNAc and increased intracellular protein O-GlcNAcylation controlled by the enzyme O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosyltransferase as compared with naive cells. 27111141 2 5 theme T 369:369 arg1 development 376:386 T cell development 369:386 T cell development 369:386 We found that glutamine and glucose also fuel an indispensable dynamic regulation of intracellular protein O-GlcNAcylation at key stages of T cell development, transformation and differentiation. 27111141 4 6 theme increased 641:649 arg1 O-GlcNAcylation 673:687 increased intracellular protein O-GlcNAcylation 641:687 increased intracellular protein O-GlcNAcylation 641:687 Immune-activated T cells contained higher concentrations of UDP-GlcNAc and increased intracellular protein O-GlcNAcylation controlled by the enzyme O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosyltransferase as compared with naive cells. 27111141 5 7 theme T 831:831 arg1 Notch 820:824 Notch 820:824 Notch 820:824 We identified Notch, the T cell antigen receptor and c-Myc as key controllers of T cell protein O-GlcNAcylation via regulation of glucose and glutamine transport. 27111141 5 7 theme T 831:831 arg1 receptor 846:853 T cell antigen receptor 831:853 T cell antigen receptor 831:853 We identified Notch, the T cell antigen receptor and c-Myc as key controllers of T cell protein O-GlcNAcylation via regulation of glucose and glutamine transport. 27111141 6 8 theme cell 1008:1011 arg1 renewal 1024:1030 T cell progenitor renewal 1006:1030 T cell progenitor renewal 1006:1030 Loss of O-GlcNAc transferase blocked T cell progenitor renewal, malignant transformation and peripheral T cell clonal expansion. 27111141 4 9 contain contained 591:599 arg1 cells 585:589 Immune-activated T cells 566:589 Immune-activated T cells 566:589 Immune-activated T cells contained higher concentrations of UDP-GlcNAc and increased intracellular protein O-GlcNAcylation controlled by the enzyme O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosyltransferase as compared with naive cells. 27111141 4 9 contain contained 591:599 arg2 concentrations 608:621 higher concentrations 601:621 higher concentrations of UDP-GlcNAc and increased intracellular protein O-GlcNAcylation controlled by the enzyme O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosyltransferase 601:774 Immune-activated T cells contained higher concentrations of UDP-GlcNAc and increased intracellular protein O-GlcNAcylation controlled by the enzyme O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosyltransferase as compared with naive cells. 27111141 7 10 theme Nutrient-dependent 1098:1115 arg1 pathways 1127:1134 Nutrient-dependent signaling pathways 1098:1134 Nutrient-dependent signaling pathways regulated by O-GlcNAc glycosyltransferase 1098:1176 Nutrient-dependent signaling pathways regulated by O-GlcNAc glycosyltransferase are thus fundamental for T cell biology. 27111141 4 11 theme O-GlcNAcylation 673:687 arg1 concentrations 608:621 higher concentrations 601:621 higher concentrations of UDP-GlcNAc and increased intracellular protein O-GlcNAcylation controlled by the enzyme O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosyltransferase 601:774 Immune-activated T cells contained higher concentrations of UDP-GlcNAc and increased intracellular protein O-GlcNAcylation controlled by the enzyme O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosyltransferase as compared with naive cells. 27111141 5 12 theme cell 833:836 arg1 Notch 820:824 Notch 820:824 Notch 820:824 We identified Notch, the T cell antigen receptor and c-Myc as key controllers of T cell protein O-GlcNAcylation via regulation of glucose and glutamine transport. 27111141 5 12 theme cell 833:836 arg1 receptor 846:853 T cell antigen receptor 831:853 T cell antigen receptor 831:853 We identified Notch, the T cell antigen receptor and c-Myc as key controllers of T cell protein O-GlcNAcylation via regulation of glucose and glutamine transport. 27111141 6 13 theme T 1006:1006 arg1 renewal 1024:1030 T cell progenitor renewal 1006:1030 T cell progenitor renewal 1006:1030 Loss of O-GlcNAc transferase blocked T cell progenitor renewal, malignant transformation and peripheral T cell clonal expansion. 27111141 2 14 theme dynamic 292:298 arg1 regulation 300:309 an indispensable dynamic regulation 275:309 an indispensable dynamic regulation of intracellular protein O-GlcNAcylation 275:350 We found that glutamine and glucose also fuel an indispensable dynamic regulation of intracellular protein O-GlcNAcylation at key stages of T cell development, transformation and differentiation. 27111141 4 15 theme protein 665:671 arg1 O-GlcNAcylation 673:687 increased intracellular protein O-GlcNAcylation 641:687 increased intracellular protein O-GlcNAcylation 641:687 Immune-activated T cells contained higher concentrations of UDP-GlcNAc and increased intracellular protein O-GlcNAcylation controlled by the enzyme O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosyltransferase as compared with naive cells. 27111141 5 16 theme antigen 838:844 arg1 Notch 820:824 Notch 820:824 Notch 820:824 We identified Notch, the T cell antigen receptor and c-Myc as key controllers of T cell protein O-GlcNAcylation via regulation of glucose and glutamine transport. 27111141 5 16 theme antigen 838:844 arg1 receptor 846:853 T cell antigen receptor 831:853 T cell antigen receptor 831:853 We identified Notch, the T cell antigen receptor and c-Myc as key controllers of T cell protein O-GlcNAcylation via regulation of glucose and glutamine transport. 27111141 5 17 theme glucose 936:942 arg1 transport 958:966 glucose and glutamine transport 936:966 glucose and glutamine transport 936:966 We identified Notch, the T cell antigen receptor and c-Myc as key controllers of T cell protein O-GlcNAcylation via regulation of glucose and glutamine transport. 27111141 4 18 theme O-linked-β-N-acetylglucosamine 714:743 arg1 glycosyltransferase 756:774 the enzyme O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosyltransferase 703:774 the enzyme O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosyltransferase 703:774 Immune-activated T cells contained higher concentrations of UDP-GlcNAc and increased intracellular protein O-GlcNAcylation controlled by the enzyme O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosyltransferase as compared with naive cells. 27111141 2 19 theme indispensable 278:290 arg1 regulation 300:309 an indispensable dynamic regulation 275:309 an indispensable dynamic regulation of intracellular protein O-GlcNAcylation 275:350 We found that glutamine and glucose also fuel an indispensable dynamic regulation of intracellular protein O-GlcNAcylation at key stages of T cell development, transformation and differentiation. 27111141 3 20 theme uridine 465:471 arg1 substrate 521:529 a substrate 519:529 a substrate for cellular glycosyltransferases 519:563 Glucose and glutamine are precursors of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), a substrate for cellular glycosyltransferases. 27111141 3 20 theme uridine 465:471 arg1 UDP-GlcNAc 506:515 UDP-GlcNAc 506:515 UDP-GlcNAc 506:515 Glucose and glutamine are precursors of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), a substrate for cellular glycosyltransferases. 27111141 3 20 theme uridine 465:471 arg1 N-acetylglucosamine 485:503 uridine diphosphate N-acetylglucosamine 465:503 uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) 465:516 Glucose and glutamine are precursors of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), a substrate for cellular glycosyltransferases. 27111141 6 21 theme transferase 986:996 arg1 Loss 969:972 Loss 969:972 Loss of O-GlcNAc transferase 969:996 Loss of O-GlcNAc transferase blocked T cell progenitor renewal, malignant transformation and peripheral T cell clonal expansion. 27111141 5 22 theme O-GlcNAcylation 902:916 arg1 Notch 820:824 Notch 820:824 Notch 820:824 We identified Notch, the T cell antigen receptor and c-Myc as key controllers of T cell protein O-GlcNAcylation via regulation of glucose and glutamine transport. 27111141 5 22 theme O-GlcNAcylation 902:916 arg1 controllers 872:882 key controllers 868:882 key controllers of T cell protein O-GlcNAcylation 868:916 We identified Notch, the T cell antigen receptor and c-Myc as key controllers of T cell protein O-GlcNAcylation via regulation of glucose and glutamine transport. 27111141 2 23 theme differentiation 408:422 arg1 stages 359:364 key stages 355:364 key stages of T cell development, transformation and differentiation 355:422 We found that glutamine and glucose also fuel an indispensable dynamic regulation of intracellular protein O-GlcNAcylation at key stages of T cell development, transformation and differentiation. 27111141 5 24 theme protein 894:900 arg1 O-GlcNAcylation 902:916 T cell protein O-GlcNAcylation 887:916 T cell protein O-GlcNAcylation 887:916 We identified Notch, the T cell antigen receptor and c-Myc as key controllers of T cell protein O-GlcNAcylation via regulation of glucose and glutamine transport. 27111141 6 25 theme T 1073:1073 arg1 expansion 1087:1095 peripheral T cell clonal expansion 1062:1095 peripheral T cell clonal expansion 1062:1095 Loss of O-GlcNAc transferase blocked T cell progenitor renewal, malignant transformation and peripheral T cell clonal expansion. 27111141 2 26 theme O-GlcNAcylation 336:350 arg1 regulation 300:309 an indispensable dynamic regulation 275:309 an indispensable dynamic regulation of intracellular protein O-GlcNAcylation 275:350 We found that glutamine and glucose also fuel an indispensable dynamic regulation of intracellular protein O-GlcNAcylation at key stages of T cell development, transformation and differentiation. 27111141 0 27 theme Glucose 0:6 arg1 O-GlcNAcylation 35:49 Glucose and glutamine fuel protein O-GlcNAcylation 0:49 Glucose and glutamine fuel protein O-GlcNAcylation 0:49 Glucose and glutamine fuel protein O-GlcNAcylation to control T cell self-renewal and malignancy. 27111141 5 28 theme transport 958:966 arg1 regulation 922:931 regulation 922:931 regulation of glucose and glutamine transport 922:966 We identified Notch, the T cell antigen receptor and c-Myc as key controllers of T cell protein O-GlcNAcylation via regulation of glucose and glutamine transport. 27111141 2 29 theme protein 328:334 arg1 O-GlcNAcylation 336:350 intracellular protein O-GlcNAcylation 314:350 intracellular protein O-GlcNAcylation 314:350 We found that glutamine and glucose also fuel an indispensable dynamic regulation of intracellular protein O-GlcNAcylation at key stages of T cell development, transformation and differentiation. 27111141 2 30 theme transformation 389:402 arg1 stages 359:364 key stages 355:364 key stages of T cell development, transformation and differentiation 355:422 We found that glutamine and glucose also fuel an indispensable dynamic regulation of intracellular protein O-GlcNAcylation at key stages of T cell development, transformation and differentiation. 27111141 0 31 theme fuel 22:25 arg1 O-GlcNAcylation 35:49 Glucose and glutamine fuel protein O-GlcNAcylation 0:49 Glucose and glutamine fuel protein O-GlcNAcylation 0:49 Glucose and glutamine fuel protein O-GlcNAcylation to control T cell self-renewal and malignancy. 27111141 6 32 theme clonal 1080:1085 arg1 expansion 1087:1095 peripheral T cell clonal expansion 1062:1095 peripheral T cell clonal expansion 1062:1095 Loss of O-GlcNAc transferase blocked T cell progenitor renewal, malignant transformation and peripheral T cell clonal expansion. 27111141 1 33 theme Sustained 98:106 arg1 glucose 108:114 Sustained glucose 98:114 Sustained glucose 98:114 Sustained glucose and glutamine transport are essential for activated T lymphocytes to support ATP and macromolecule biosynthesis. 27111141 0 34 theme glutamine 12:20 arg1 O-GlcNAcylation 35:49 Glucose and glutamine fuel protein O-GlcNAcylation 0:49 Glucose and glutamine fuel protein O-GlcNAcylation 0:49 Glucose and glutamine fuel protein O-GlcNAcylation to control T cell self-renewal and malignancy. 27111141 6 35 theme cell 1075:1078 arg1 expansion 1087:1095 peripheral T cell clonal expansion 1062:1095 peripheral T cell clonal expansion 1062:1095 Loss of O-GlcNAc transferase blocked T cell progenitor renewal, malignant transformation and peripheral T cell clonal expansion. 27111141 1 36 theme T 168:168 arg1 lymphocytes 170:180 activated T lymphocytes 158:180 activated T lymphocytes 158:180 Sustained glucose and glutamine transport are essential for activated T lymphocytes to support ATP and macromolecule biosynthesis. 27111141 1 37 theme macromolecule 201:213 arg1 biosynthesis 215:226 macromolecule biosynthesis 201:226 macromolecule biosynthesis 201:226 Sustained glucose and glutamine transport are essential for activated T lymphocytes to support ATP and macromolecule biosynthesis. 27111141 3 38 theme cellular 535:542 arg1 glycosyltransferases 544:563 cellular glycosyltransferases 535:563 cellular glycosyltransferases 535:563 Glucose and glutamine are precursors of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), a substrate for cellular glycosyltransferases. 27111141 4 39 theme UDP-GlcNAc 626:635 arg1 concentrations 608:621 higher concentrations 601:621 higher concentrations of UDP-GlcNAc and increased intracellular protein O-GlcNAcylation controlled by the enzyme O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosyltransferase 601:774 Immune-activated T cells contained higher concentrations of UDP-GlcNAc and increased intracellular protein O-GlcNAcylation controlled by the enzyme O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosyltransferase as compared with naive cells. 27111141 7 40 theme T 1203:1203 arg1 biology 1210:1216 T cell biology 1203:1216 T cell biology 1203:1216 Nutrient-dependent signaling pathways regulated by O-GlcNAc glycosyltransferase are thus fundamental for T cell biology. 27111141 3 41 theme N-acetylglucosamine 485:503 arg1 precursors 451:460 precursors 451:460 precursors of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), a substrate for cellular glycosyltransferases 451:563 Glucose and glutamine are precursors of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), a substrate for cellular glycosyltransferases. 27111141 3 41 theme N-acetylglucosamine 485:503 arg1 glutamine 437:445 glutamine 437:445 glutamine 437:445 Glucose and glutamine are precursors of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), a substrate for cellular glycosyltransferases. 27111141 3 41 theme N-acetylglucosamine 485:503 arg1 Glucose 425:431 Glucose 425:431 Glucose 425:431 Glucose and glutamine are precursors of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), a substrate for cellular glycosyltransferases. 27111141 0 42 theme protein 27:33 arg1 O-GlcNAcylation 35:49 Glucose and glutamine fuel protein O-GlcNAcylation 0:49 Glucose and glutamine fuel protein O-GlcNAcylation 0:49 Glucose and glutamine fuel protein O-GlcNAcylation to control T cell self-renewal and malignancy. 27111141 6 43 theme peripheral 1062:1071 arg1 expansion 1087:1095 peripheral T cell clonal expansion 1062:1095 peripheral T cell clonal expansion 1062:1095 Loss of O-GlcNAc transferase blocked T cell progenitor renewal, malignant transformation and peripheral T cell clonal expansion. 27111141 7 44 theme cell 1205:1208 arg1 biology 1210:1216 T cell biology 1203:1216 T cell biology 1203:1216 Nutrient-dependent signaling pathways regulated by O-GlcNAc glycosyltransferase are thus fundamental for T cell biology. 27111141 7 45 theme O-GlcNAc 1149:1156 arg1 glycosyltransferase 1158:1176 O-GlcNAc glycosyltransferase 1149:1176 O-GlcNAc glycosyltransferase 1149:1176 Nutrient-dependent signaling pathways regulated by O-GlcNAc glycosyltransferase are thus fundamental for T cell biology. 27111141 4 46 theme O-GlcNAc 746:753 arg1 glycosyltransferase 756:774 the enzyme O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosyltransferase 703:774 the enzyme O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosyltransferase 703:774 Immune-activated T cells contained higher concentrations of UDP-GlcNAc and increased intracellular protein O-GlcNAcylation controlled by the enzyme O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosyltransferase as compared with naive cells. 27111141 5 47 theme T 887:887 arg1 O-GlcNAcylation 902:916 T cell protein O-GlcNAcylation 887:916 T cell protein O-GlcNAcylation 887:916 We identified Notch, the T cell antigen receptor and c-Myc as key controllers of T cell protein O-GlcNAcylation via regulation of glucose and glutamine transport. 27111141 4 48 theme T 583:583 arg1 cells 585:589 Immune-activated T cells 566:589 Immune-activated T cells 566:589 Immune-activated T cells contained higher concentrations of UDP-GlcNAc and increased intracellular protein O-GlcNAcylation controlled by the enzyme O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosyltransferase as compared with naive cells. 27111141 5 49 theme cell 889:892 arg1 O-GlcNAcylation 902:916 T cell protein O-GlcNAcylation 887:916 T cell protein O-GlcNAcylation 887:916 We identified Notch, the T cell antigen receptor and c-Myc as key controllers of T cell protein O-GlcNAcylation via regulation of glucose and glutamine transport. 27111141 4 50 theme higher 601:606 arg1 concentrations 608:621 higher concentrations 601:621 higher concentrations of UDP-GlcNAc and increased intracellular protein O-GlcNAcylation controlled by the enzyme O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosyltransferase 601:774 Immune-activated T cells contained higher concentrations of UDP-GlcNAc and increased intracellular protein O-GlcNAcylation controlled by the enzyme O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosyltransferase as compared with naive cells. 27111141 6 51 theme progenitor 1013:1022 arg1 renewal 1024:1030 T cell progenitor renewal 1006:1030 T cell progenitor renewal 1006:1030 Loss of O-GlcNAc transferase blocked T cell progenitor renewal, malignant transformation and peripheral T cell clonal expansion. 27111141 1 52 theme glutamine 120:128 arg1 transport 130:138 glutamine transport 120:138 glutamine transport 120:138 Sustained glucose and glutamine transport are essential for activated T lymphocytes to support ATP and macromolecule biosynthesis. 27111141 6 53 theme malignant 1033:1041 arg1 transformation 1043:1056 malignant transformation 1033:1056 malignant transformation 1033:1056 Loss of O-GlcNAc transferase blocked T cell progenitor renewal, malignant transformation and peripheral T cell clonal expansion. 27111141 2 54 theme key 355:357 arg1 stages 359:364 key stages 355:364 key stages of T cell development, transformation and differentiation 355:422 We found that glutamine and glucose also fuel an indispensable dynamic regulation of intracellular protein O-GlcNAcylation at key stages of T cell development, transformation and differentiation. 27111141 2 55 theme intracellular 314:326 arg1 O-GlcNAcylation 336:350 intracellular protein O-GlcNAcylation 314:350 intracellular protein O-GlcNAcylation 314:350 We found that glutamine and glucose also fuel an indispensable dynamic regulation of intracellular protein O-GlcNAcylation at key stages of T cell development, transformation and differentiation. 27111141 0 56 dep cell 64:67 arg1 self-renewal 69:80 self-renewal 69:80 self-renewal 69:80 Glucose and glutamine fuel protein O-GlcNAcylation to control T cell self-renewal and malignancy. 27111141 7 57 theme signaling 1117:1125 arg1 pathways 1127:1134 Nutrient-dependent signaling pathways 1098:1134 Nutrient-dependent signaling pathways regulated by O-GlcNAc glycosyltransferase 1098:1176 Nutrient-dependent signaling pathways regulated by O-GlcNAc glycosyltransferase are thus fundamental for T cell biology. 27111141 4 58 theme naive 793:797 arg1 cells 799:803 naive cells 793:803 naive cells 793:803 Immune-activated T cells contained higher concentrations of UDP-GlcNAc and increased intracellular protein O-GlcNAcylation controlled by the enzyme O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosyltransferase as compared with naive cells. 27111141 5 59 theme glutamine 948:956 arg1 transport 958:966 glucose and glutamine transport 936:966 glucose and glutamine transport 936:966 We identified Notch, the T cell antigen receptor and c-Myc as key controllers of T cell protein O-GlcNAcylation via regulation of glucose and glutamine transport. 27111141 2 60 theme cell 371:374 arg1 development 376:386 T cell development 369:386 T cell development 369:386 We found that glutamine and glucose also fuel an indispensable dynamic regulation of intracellular protein O-GlcNAcylation at key stages of T cell development, transformation and differentiation. 27111141 3 61 theme diphosphate 473:483 arg1 substrate 521:529 a substrate 519:529 a substrate for cellular glycosyltransferases 519:563 Glucose and glutamine are precursors of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), a substrate for cellular glycosyltransferases. 27111141 3 61 theme diphosphate 473:483 arg1 UDP-GlcNAc 506:515 UDP-GlcNAc 506:515 UDP-GlcNAc 506:515 Glucose and glutamine are precursors of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), a substrate for cellular glycosyltransferases. 27111141 3 61 theme diphosphate 473:483 arg1 N-acetylglucosamine 485:503 uridine diphosphate N-acetylglucosamine 465:503 uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) 465:516 Glucose and glutamine are precursors of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), a substrate for cellular glycosyltransferases. 27111141 4 62 theme enzyme 707:712 arg1 glycosyltransferase 756:774 the enzyme O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosyltransferase 703:774 the enzyme O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosyltransferase 703:774 Immune-activated T cells contained higher concentrations of UDP-GlcNAc and increased intracellular protein O-GlcNAcylation controlled by the enzyme O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosyltransferase as compared with naive cells. 27111141 0 63 theme T 62:62 arg1 cell 64:67 T cell self-renewal and malignancy 62:95 cell 64:67 Glucose and glutamine fuel protein O-GlcNAcylation to control T cell self-renewal and malignancy. 27111141 2 64 theme development 376:386 arg1 stages 359:364 key stages 355:364 key stages of T cell development, transformation and differentiation 355:422 We found that glutamine and glucose also fuel an indispensable dynamic regulation of intracellular protein O-GlcNAcylation at key stages of T cell development, transformation and differentiation. 28512129 2 0 theme E-cadherin 516:525 arg1 dependent 531:539 dependent 531:539 dependent 531:539 We recently discovered that the cadherin superfamily carries O-linked mannose (O-Man) glycans at highly conserved residues in specific extracellular cadherin domains, and it was suggested that the function of E-cadherin was dependent on the O-Man glycans. 28512129 2 0 theme E-cadherin 516:525 arg1 function 504:511 the function 500:511 the function of E-cadherin 500:525 We recently discovered that the cadherin superfamily carries O-linked mannose (O-Man) glycans at highly conserved residues in specific extracellular cadherin domains, and it was suggested that the function of E-cadherin was dependent on the O-Man glycans. 28512129 4 1 from functions 931:939 arg1 cadherins 961:969 cadherins 961:969 cadherins 961:969 To explore the functions of O-Man glycans on cadherins and protocadherins, we used a combinatorial gene-editing strategy in multiple cell lines to evaluate the role of the two POMTs initiating O-Man glycosylation and the major enzyme elongating O-Man glycans, the protein O-mannose β-1,2-N-acetylglucosaminyltransferase, POMGnT1. 28512129 4 1 from functions 931:939 arg1 protocadherins 975:988 protocadherins 975:988 protocadherins 975:988 To explore the functions of O-Man glycans on cadherins and protocadherins, we used a combinatorial gene-editing strategy in multiple cell lines to evaluate the role of the two POMTs initiating O-Man glycosylation and the major enzyme elongating O-Man glycans, the protein O-mannose β-1,2-N-acetylglucosaminyltransferase, POMGnT1. 28512129 3 2 from Deficiencies 563:574 arg1 enzymes 579:585 enzymes 579:585 enzymes catalyzing O-Man biosynthesis 579:615 Deficiencies in enzymes catalyzing O-Man biosynthesis, including the two human protein O-mannosyltransferases, POMT1 and POMT2, underlie a subgroup of congenital muscular dystrophies designated α-dystroglycanopathies, because deficient O-Man glycosylation of α-dystroglycan disrupts laminin interaction with α-dystroglycan and the extracellular matrix. 28512129 4 3 used used 994:997 arg2 we 991:992 we 991:992 we 991:992 To explore the functions of O-Man glycans on cadherins and protocadherins, we used a combinatorial gene-editing strategy in multiple cell lines to evaluate the role of the two POMTs initiating O-Man glycosylation and the major enzyme elongating O-Man glycans, the protein O-mannose β-1,2-N-acetylglucosaminyltransferase, POMGnT1. 28512129 0 4 theme O-mannosyltransferases 77:98 arg1 independent 54:64 independent 54:64 independent 54:64 Mammalian O-mannosylation of cadherins and plexins is independent of protein O-mannosyltransferases 1 and 2. 28512129 3 5 theme muscular 725:732 arg1 dystrophies 734:744 congenital muscular dystrophies 714:744 congenital muscular dystrophies designated α-dystroglycanopathies 714:778 Deficiencies in enzymes catalyzing O-Man biosynthesis, including the two human protein O-mannosyltransferases, POMT1 and POMT2, underlie a subgroup of congenital muscular dystrophies designated α-dystroglycanopathies, because deficient O-Man glycosylation of α-dystroglycan disrupts laminin interaction with α-dystroglycan and the extracellular matrix. 28512129 6 6 dep dedicated 1532:1540 arg1 whereas 1586:1592 whereas 1586:1592 whereas 1586:1592 Thus, the classical and evolutionarily conserved POMT O-mannosylation pathway is essentially dedicated to α-dystroglycan and a few other proteins, whereas a novel O-mannosylation process in mammalian cells is predicted to serve the large cadherin superfamily and other proteins. 28512129 6 7 from process 1618:1624 arg1 cells 1639:1643 mammalian cells 1629:1643 mammalian cells 1629:1643 Thus, the classical and evolutionarily conserved POMT O-mannosylation pathway is essentially dedicated to α-dystroglycan and a few other proteins, whereas a novel O-mannosylation process in mammalian cells is predicted to serve the large cadherin superfamily and other proteins. 28512129 2 8 theme O-Man 386:390 arg1 glycans 393:399 O-linked mannose (O-Man) glycans 368:399 O-linked mannose (O-Man) glycans 368:399 We recently discovered that the cadherin superfamily carries O-linked mannose (O-Man) glycans at highly conserved residues in specific extracellular cadherin domains, and it was suggested that the function of E-cadherin was dependent on the O-Man glycans. 28512129 4 9 theme O-Man 1161:1165 arg1 glycans 1167:1173 elongating O-Man glycans 1150:1173 elongating O-Man glycans 1150:1173 To explore the functions of O-Man glycans on cadherins and protocadherins, we used a combinatorial gene-editing strategy in multiple cell lines to evaluate the role of the two POMTs initiating O-Man glycosylation and the major enzyme elongating O-Man glycans, the protein O-mannose β-1,2-N-acetylglucosaminyltransferase, POMGnT1. 28512129 1 10 theme important 264:272 arg1 modification 293:304 this important post-translational modification 259:304 this important post-translational modification 259:304 Protein O-mannosylation is found in yeast and metazoans, and a family of conserved orthologous protein O-mannosyltransferases is believed to initiate this important post-translational modification. 28512129 0 11 theme 2 106:106 arg1 independent 54:64 independent 54:64 independent 54:64 Mammalian O-mannosylation of cadherins and plexins is independent of protein O-mannosyltransferases 1 and 2. 28512129 1 12 located found 136:140 arg2 O-mannosylation 117:131 Protein O-mannosylation 109:131 Protein O-mannosylation 109:131 Protein O-mannosylation is found in yeast and metazoans, and a family of conserved orthologous protein O-mannosyltransferases is believed to initiate this important post-translational modification. 28512129 1 12 located found 136:140 arg1 metazoans 155:163 metazoans 155:163 metazoans 155:163 Protein O-mannosylation is found in yeast and metazoans, and a family of conserved orthologous protein O-mannosyltransferases is believed to initiate this important post-translational modification. 28512129 1 12 located found 136:140 arg1 yeast 145:149 yeast 145:149 yeast 145:149 Protein O-mannosylation is found in yeast and metazoans, and a family of conserved orthologous protein O-mannosyltransferases is believed to initiate this important post-translational modification. 28512129 3 13 with interaction 854:864 arg1 matrix 908:913 the extracellular matrix 890:913 the extracellular matrix 890:913 Deficiencies in enzymes catalyzing O-Man biosynthesis, including the two human protein O-mannosyltransferases, POMT1 and POMT2, underlie a subgroup of congenital muscular dystrophies designated α-dystroglycanopathies, because deficient O-Man glycosylation of α-dystroglycan disrupts laminin interaction with α-dystroglycan and the extracellular matrix. 28512129 3 13 with interaction 854:864 arg1 α-dystroglycan 871:884 α-dystroglycan 871:884 α-dystroglycan 871:884 Deficiencies in enzymes catalyzing O-Man biosynthesis, including the two human protein O-mannosyltransferases, POMT1 and POMT2, underlie a subgroup of congenital muscular dystrophies designated α-dystroglycanopathies, because deficient O-Man glycosylation of α-dystroglycan disrupts laminin interaction with α-dystroglycan and the extracellular matrix. 28512129 3 14 theme O-Man 598:602 arg1 biosynthesis 604:615 O-Man biosynthesis 598:615 O-Man biosynthesis 598:615 Deficiencies in enzymes catalyzing O-Man biosynthesis, including the two human protein O-mannosyltransferases, POMT1 and POMT2, underlie a subgroup of congenital muscular dystrophies designated α-dystroglycanopathies, because deficient O-Man glycosylation of α-dystroglycan disrupts laminin interaction with α-dystroglycan and the extracellular matrix. 28512129 1 15 theme post-translational 274:291 arg1 modification 293:304 this important post-translational modification 259:304 this important post-translational modification 259:304 Protein O-mannosylation is found in yeast and metazoans, and a family of conserved orthologous protein O-mannosyltransferases is believed to initiate this important post-translational modification. 28512129 2 16 theme O-Man 548:552 arg1 glycans 554:560 the O-Man glycans 544:560 the O-Man glycans 544:560 We recently discovered that the cadherin superfamily carries O-linked mannose (O-Man) glycans at highly conserved residues in specific extracellular cadherin domains, and it was suggested that the function of E-cadherin was dependent on the O-Man glycans. 28512129 3 17 theme deficient 789:797 arg1 glycosylation 805:817 deficient O-Man glycosylation 789:817 deficient O-Man glycosylation of α-dystroglycan 789:835 Deficiencies in enzymes catalyzing O-Man biosynthesis, including the two human protein O-mannosyltransferases, POMT1 and POMT2, underlie a subgroup of congenital muscular dystrophies designated α-dystroglycanopathies, because deficient O-Man glycosylation of α-dystroglycan disrupts laminin interaction with α-dystroglycan and the extracellular matrix. 28512129 5 18 theme cadherins 1279:1287 arg1 O-mannosylation 1260:1274 O-mannosylation 1260:1274 O-mannosylation of cadherins and protocadherins 1260:1306 Surprisingly, O-mannosylation of cadherins and protocadherins does not require POMT1 and/or POMT2 in contrast to α-dystroglycan, and moreover, the O-Man glycans on cadherins are not elongated. 28512129 4 19 dep enzyme 1143:1148 arg1 glycans 1167:1173 elongating O-Man glycans 1150:1173 elongating O-Man glycans 1150:1173 To explore the functions of O-Man glycans on cadherins and protocadherins, we used a combinatorial gene-editing strategy in multiple cell lines to evaluate the role of the two POMTs initiating O-Man glycosylation and the major enzyme elongating O-Man glycans, the protein O-mannose β-1,2-N-acetylglucosaminyltransferase, POMGnT1. 28512129 6 20 theme conserved 1478:1486 arg1 pathway 1509:1515 the classical and evolutionarily conserved POMT O-mannosylation pathway 1445:1515 the classical and evolutionarily conserved POMT O-mannosylation pathway 1445:1515 Thus, the classical and evolutionarily conserved POMT O-mannosylation pathway is essentially dedicated to α-dystroglycan and a few other proteins, whereas a novel O-mannosylation process in mammalian cells is predicted to serve the large cadherin superfamily and other proteins. 28512129 3 21 theme O-Man 799:803 arg1 glycosylation 805:817 deficient O-Man glycosylation 789:817 deficient O-Man glycosylation of α-dystroglycan 789:835 Deficiencies in enzymes catalyzing O-Man biosynthesis, including the two human protein O-mannosyltransferases, POMT1 and POMT2, underlie a subgroup of congenital muscular dystrophies designated α-dystroglycanopathies, because deficient O-Man glycosylation of α-dystroglycan disrupts laminin interaction with α-dystroglycan and the extracellular matrix. 28512129 2 22 theme cadherin 456:463 arg1 domains 465:471 specific extracellular cadherin domains 433:471 specific extracellular cadherin domains 433:471 We recently discovered that the cadherin superfamily carries O-linked mannose (O-Man) glycans at highly conserved residues in specific extracellular cadherin domains, and it was suggested that the function of E-cadherin was dependent on the O-Man glycans. 28512129 4 23 theme elongating 1150:1159 arg1 glycans 1167:1173 elongating O-Man glycans 1150:1173 elongating O-Man glycans 1150:1173 To explore the functions of O-Man glycans on cadherins and protocadherins, we used a combinatorial gene-editing strategy in multiple cell lines to evaluate the role of the two POMTs initiating O-Man glycosylation and the major enzyme elongating O-Man glycans, the protein O-mannose β-1,2-N-acetylglucosaminyltransferase, POMGnT1. 28512129 6 24 theme cadherin 1677:1684 arg1 superfamily 1686:1696 the large cadherin superfamily 1667:1696 the large cadherin superfamily 1667:1696 Thus, the classical and evolutionarily conserved POMT O-mannosylation pathway is essentially dedicated to α-dystroglycan and a few other proteins, whereas a novel O-mannosylation process in mammalian cells is predicted to serve the large cadherin superfamily and other proteins. 28512129 4 25 theme combinatorial 1001:1013 arg1 strategy 1028:1035 a combinatorial gene-editing strategy 999:1035 a combinatorial gene-editing strategy in multiple cell lines 999:1058 To explore the functions of O-Man glycans on cadherins and protocadherins, we used a combinatorial gene-editing strategy in multiple cell lines to evaluate the role of the two POMTs initiating O-Man glycosylation and the major enzyme elongating O-Man glycans, the protein O-mannose β-1,2-N-acetylglucosaminyltransferase, POMGnT1. 28512129 4 26 theme POMTs 1092:1096 arg1 role 1076:1079 the role 1072:1079 the role of the two POMTs initiating O-Man glycosylation and the major enzyme elongating O-Man glycans, the protein O-mannose β-1,2-N-acetylglucosaminyltransferase, POMGnT1 1072:1243 To explore the functions of O-Man glycans on cadherins and protocadherins, we used a combinatorial gene-editing strategy in multiple cell lines to evaluate the role of the two POMTs initiating O-Man glycosylation and the major enzyme elongating O-Man glycans, the protein O-mannose β-1,2-N-acetylglucosaminyltransferase, POMGnT1. 28512129 6 27 dep α-dystroglycan 1545:1558 arg1 proteins 1576:1583 other proteins 1570:1583 other proteins 1570:1583 Thus, the classical and evolutionarily conserved POMT O-mannosylation pathway is essentially dedicated to α-dystroglycan and a few other proteins, whereas a novel O-mannosylation process in mammalian cells is predicted to serve the large cadherin superfamily and other proteins. 28512129 5 28 from POMT1 1325:1329 arg1 contrast 1347:1354 contrast 1347:1354 contrast to α-dystroglycan 1347:1372 Surprisingly, O-mannosylation of cadherins and protocadherins does not require POMT1 and/or POMT2 in contrast to α-dystroglycan, and moreover, the O-Man glycans on cadherins are not elongated. 28512129 4 29 theme O-Man 1109:1113 arg1 glycosylation 1115:1127 O-Man glycosylation 1109:1127 O-Man glycosylation 1109:1127 To explore the functions of O-Man glycans on cadherins and protocadherins, we used a combinatorial gene-editing strategy in multiple cell lines to evaluate the role of the two POMTs initiating O-Man glycosylation and the major enzyme elongating O-Man glycans, the protein O-mannose β-1,2-N-acetylglucosaminyltransferase, POMGnT1. 28512129 5 30 gly O-mannosylation 1260:1274 arg1 protocadherins 1293:1306 protocadherins 1293:1306 protocadherins 1293:1306 Surprisingly, O-mannosylation of cadherins and protocadherins does not require POMT1 and/or POMT2 in contrast to α-dystroglycan, and moreover, the O-Man glycans on cadherins are not elongated. 28512129 5 30 gly O-mannosylation 1260:1274 arg1 cadherins 1279:1287 cadherins 1279:1287 cadherins 1279:1287 Surprisingly, O-mannosylation of cadherins and protocadherins does not require POMT1 and/or POMT2 in contrast to α-dystroglycan, and moreover, the O-Man glycans on cadherins are not elongated. 28512129 3 31 gly glycosylation 805:817 arg1 α-dystroglycan 822:835 α-dystroglycan 822:835 α-dystroglycan 822:835 Deficiencies in enzymes catalyzing O-Man biosynthesis, including the two human protein O-mannosyltransferases, POMT1 and POMT2, underlie a subgroup of congenital muscular dystrophies designated α-dystroglycanopathies, because deficient O-Man glycosylation of α-dystroglycan disrupts laminin interaction with α-dystroglycan and the extracellular matrix. 28512129 4 32 theme glycans 950:956 arg1 functions 931:939 the functions 927:939 the functions of O-Man glycans on cadherins and protocadherins 927:988 To explore the functions of O-Man glycans on cadherins and protocadherins, we used a combinatorial gene-editing strategy in multiple cell lines to evaluate the role of the two POMTs initiating O-Man glycosylation and the major enzyme elongating O-Man glycans, the protein O-mannose β-1,2-N-acetylglucosaminyltransferase, POMGnT1. 28512129 6 33 theme POMT 1488:1491 arg1 pathway 1509:1515 the classical and evolutionarily conserved POMT O-mannosylation pathway 1445:1515 the classical and evolutionarily conserved POMT O-mannosylation pathway 1445:1515 Thus, the classical and evolutionarily conserved POMT O-mannosylation pathway is essentially dedicated to α-dystroglycan and a few other proteins, whereas a novel O-mannosylation process in mammalian cells is predicted to serve the large cadherin superfamily and other proteins. 28512129 2 34 theme conserved 411:419 arg1 residues 421:428 highly conserved residues 404:428 highly conserved residues in specific extracellular cadherin domains 404:471 We recently discovered that the cadherin superfamily carries O-linked mannose (O-Man) glycans at highly conserved residues in specific extracellular cadherin domains, and it was suggested that the function of E-cadherin was dependent on the O-Man glycans. 28512129 0 35 theme Mammalian 0:8 arg1 O-mannosylation 10:24 Mammalian O-mannosylation 0:24 Mammalian O-mannosylation of cadherins and plexins 0:49 Mammalian O-mannosylation of cadherins and plexins is independent of protein O-mannosyltransferases 1 and 2. 28512129 3 36 theme α-dystroglycan 822:835 arg1 glycosylation 805:817 deficient O-Man glycosylation 789:817 deficient O-Man glycosylation of α-dystroglycan 789:835 Deficiencies in enzymes catalyzing O-Man biosynthesis, including the two human protein O-mannosyltransferases, POMT1 and POMT2, underlie a subgroup of congenital muscular dystrophies designated α-dystroglycanopathies, because deficient O-Man glycosylation of α-dystroglycan disrupts laminin interaction with α-dystroglycan and the extracellular matrix. 28512129 4 37 theme O-Man 944:948 arg1 glycans 950:956 O-Man glycans 944:956 O-Man glycans 944:956 To explore the functions of O-Man glycans on cadherins and protocadherins, we used a combinatorial gene-editing strategy in multiple cell lines to evaluate the role of the two POMTs initiating O-Man glycosylation and the major enzyme elongating O-Man glycans, the protein O-mannose β-1,2-N-acetylglucosaminyltransferase, POMGnT1. 28512129 2 38 theme cadherin 339:346 arg1 superfamily 348:358 the cadherin superfamily 335:358 the cadherin superfamily 335:358 We recently discovered that the cadherin superfamily carries O-linked mannose (O-Man) glycans at highly conserved residues in specific extracellular cadherin domains, and it was suggested that the function of E-cadherin was dependent on the O-Man glycans. 28512129 6 39 theme classical 1449:1457 arg1 pathway 1509:1515 the classical and evolutionarily conserved POMT O-mannosylation pathway 1445:1515 the classical and evolutionarily conserved POMT O-mannosylation pathway 1445:1515 Thus, the classical and evolutionarily conserved POMT O-mannosylation pathway is essentially dedicated to α-dystroglycan and a few other proteins, whereas a novel O-mannosylation process in mammalian cells is predicted to serve the large cadherin superfamily and other proteins. 28512129 4 40 from strategy 1028:1035 arg1 lines 1054:1058 multiple cell lines 1040:1058 multiple cell lines 1040:1058 To explore the functions of O-Man glycans on cadherins and protocadherins, we used a combinatorial gene-editing strategy in multiple cell lines to evaluate the role of the two POMTs initiating O-Man glycosylation and the major enzyme elongating O-Man glycans, the protein O-mannose β-1,2-N-acetylglucosaminyltransferase, POMGnT1. 28512129 0 41 theme cadherins 29:37 arg1 O-mannosylation 10:24 Mammalian O-mannosylation 0:24 Mammalian O-mannosylation of cadherins and plexins 0:49 Mammalian O-mannosylation of cadherins and plexins is independent of protein O-mannosyltransferases 1 and 2. 28512129 4 42 theme gene-editing 1015:1026 arg1 strategy 1028:1035 a combinatorial gene-editing strategy 999:1035 a combinatorial gene-editing strategy in multiple cell lines 999:1058 To explore the functions of O-Man glycans on cadherins and protocadherins, we used a combinatorial gene-editing strategy in multiple cell lines to evaluate the role of the two POMTs initiating O-Man glycosylation and the major enzyme elongating O-Man glycans, the protein O-mannose β-1,2-N-acetylglucosaminyltransferase, POMGnT1. 28512129 5 43 from glycans 1399:1405 arg1 cadherins 1410:1418 cadherins 1410:1418 cadherins 1410:1418 Surprisingly, O-mannosylation of cadherins and protocadherins does not require POMT1 and/or POMT2 in contrast to α-dystroglycan, and moreover, the O-Man glycans on cadherins are not elongated. 28512129 4 44 theme O-mannose 1188:1196 arg1 β-1,2-N-acetylglucosaminyltransferase 1198:1234 the protein O-mannose β-1,2-N-acetylglucosaminyltransferase 1176:1234 the protein O-mannose β-1,2-N-acetylglucosaminyltransferase 1176:1234 To explore the functions of O-Man glycans on cadherins and protocadherins, we used a combinatorial gene-editing strategy in multiple cell lines to evaluate the role of the two POMTs initiating O-Man glycosylation and the major enzyme elongating O-Man glycans, the protein O-mannose β-1,2-N-acetylglucosaminyltransferase, POMGnT1. 28512129 4 44 theme O-mannose 1188:1196 arg1 enzyme 1143:1148 the major enzyme elongating O-Man glycans, the protein O-mannose β-1,2-N-acetylglucosaminyltransferase, POMGnT1 1133:1243 enzyme 1143:1148 To explore the functions of O-Man glycans on cadherins and protocadherins, we used a combinatorial gene-editing strategy in multiple cell lines to evaluate the role of the two POMTs initiating O-Man glycosylation and the major enzyme elongating O-Man glycans, the protein O-mannose β-1,2-N-acetylglucosaminyltransferase, POMGnT1. 28512129 1 45 theme conserved 182:190 arg1 O-mannosyltransferases 212:233 conserved orthologous protein O-mannosyltransferases 182:233 conserved orthologous protein O-mannosyltransferases 182:233 Protein O-mannosylation is found in yeast and metazoans, and a family of conserved orthologous protein O-mannosyltransferases is believed to initiate this important post-translational modification. 28512129 6 46 theme other 1570:1574 arg1 proteins 1576:1583 other proteins 1570:1583 other proteins 1570:1583 Thus, the classical and evolutionarily conserved POMT O-mannosylation pathway is essentially dedicated to α-dystroglycan and a few other proteins, whereas a novel O-mannosylation process in mammalian cells is predicted to serve the large cadherin superfamily and other proteins. 28512129 1 47 gly O-mannosylation 117:131 arg1 metazoans 155:163 metazoans 155:163 metazoans 155:163 Protein O-mannosylation is found in yeast and metazoans, and a family of conserved orthologous protein O-mannosyltransferases is believed to initiate this important post-translational modification. 28512129 1 47 gly O-mannosylation 117:131 arg1 yeast 145:149 yeast 145:149 yeast 145:149 Protein O-mannosylation is found in yeast and metazoans, and a family of conserved orthologous protein O-mannosyltransferases is believed to initiate this important post-translational modification. 28512129 1 48 theme Protein 109:115 arg1 O-mannosylation 117:131 Protein O-mannosylation 109:131 Protein O-mannosylation 109:131 Protein O-mannosylation is found in yeast and metazoans, and a family of conserved orthologous protein O-mannosyltransferases is believed to initiate this important post-translational modification. 28512129 5 49 theme O-Man 1393:1397 arg1 glycans 1399:1405 the O-Man glycans 1389:1405 the O-Man glycans on cadherins 1389:1418 Surprisingly, O-mannosylation of cadherins and protocadherins does not require POMT1 and/or POMT2 in contrast to α-dystroglycan, and moreover, the O-Man glycans on cadherins are not elongated. 28512129 1 50 theme orthologous 192:202 arg1 O-mannosyltransferases 212:233 conserved orthologous protein O-mannosyltransferases 182:233 conserved orthologous protein O-mannosyltransferases 182:233 Protein O-mannosylation is found in yeast and metazoans, and a family of conserved orthologous protein O-mannosyltransferases is believed to initiate this important post-translational modification. 28512129 0 51 theme plexins 43:49 arg1 O-mannosylation 10:24 Mammalian O-mannosylation 0:24 Mammalian O-mannosylation of cadherins and plexins 0:49 Mammalian O-mannosylation of cadherins and plexins is independent of protein O-mannosyltransferases 1 and 2. 28512129 2 52 theme extracellular 442:454 arg1 domains 465:471 specific extracellular cadherin domains 433:471 specific extracellular cadherin domains 433:471 We recently discovered that the cadherin superfamily carries O-linked mannose (O-Man) glycans at highly conserved residues in specific extracellular cadherin domains, and it was suggested that the function of E-cadherin was dependent on the O-Man glycans. 28512129 1 53 theme protein 204:210 arg1 O-mannosyltransferases 212:233 conserved orthologous protein O-mannosyltransferases 182:233 conserved orthologous protein O-mannosyltransferases 182:233 Protein O-mannosylation is found in yeast and metazoans, and a family of conserved orthologous protein O-mannosyltransferases is believed to initiate this important post-translational modification. 28512129 3 54 dep subgroup 702:709 arg1 disrupts 837:844 disrupts 837:844 disrupts laminin interaction with α-dystroglycan and the extracellular matrix 837:913 Deficiencies in enzymes catalyzing O-Man biosynthesis, including the two human protein O-mannosyltransferases, POMT1 and POMT2, underlie a subgroup of congenital muscular dystrophies designated α-dystroglycanopathies, because deficient O-Man glycosylation of α-dystroglycan disrupts laminin interaction with α-dystroglycan and the extracellular matrix. 28512129 6 55 theme novel 1596:1600 arg1 process 1618:1624 a novel O-mannosylation process 1594:1624 a novel O-mannosylation process in mammalian cells 1594:1643 Thus, the classical and evolutionarily conserved POMT O-mannosylation pathway is essentially dedicated to α-dystroglycan and a few other proteins, whereas a novel O-mannosylation process in mammalian cells is predicted to serve the large cadherin superfamily and other proteins. 28512129 0 56 gly O-mannosylation 10:24 arg1 plexins 43:49 plexins 43:49 plexins 43:49 Mammalian O-mannosylation of cadherins and plexins is independent of protein O-mannosyltransferases 1 and 2. 28512129 0 56 gly O-mannosylation 10:24 arg1 cadherins 29:37 cadherins 29:37 cadherins 29:37 Mammalian O-mannosylation of cadherins and plexins is independent of protein O-mannosyltransferases 1 and 2. 28512129 1 57 theme O-mannosyltransferases 212:233 arg1 family 172:177 a family 170:177 a family of conserved orthologous protein O-mannosyltransferases 170:233 Protein O-mannosylation is found in yeast and metazoans, and a family of conserved orthologous protein O-mannosyltransferases is believed to initiate this important post-translational modification. 28512129 4 58 theme cell 1049:1052 arg1 lines 1054:1058 multiple cell lines 1040:1058 multiple cell lines 1040:1058 To explore the functions of O-Man glycans on cadherins and protocadherins, we used a combinatorial gene-editing strategy in multiple cell lines to evaluate the role of the two POMTs initiating O-Man glycosylation and the major enzyme elongating O-Man glycans, the protein O-mannose β-1,2-N-acetylglucosaminyltransferase, POMGnT1. 28512129 6 59 theme O-mannosylation 1493:1507 arg1 pathway 1509:1515 the classical and evolutionarily conserved POMT O-mannosylation pathway 1445:1515 the classical and evolutionarily conserved POMT O-mannosylation pathway 1445:1515 Thus, the classical and evolutionarily conserved POMT O-mannosylation pathway is essentially dedicated to α-dystroglycan and a few other proteins, whereas a novel O-mannosylation process in mammalian cells is predicted to serve the large cadherin superfamily and other proteins. 28512129 3 60 theme dystrophies 734:744 arg1 subgroup 702:709 a subgroup 700:709 a subgroup 700:709 Deficiencies in enzymes catalyzing O-Man biosynthesis, including the two human protein O-mannosyltransferases, POMT1 and POMT2, underlie a subgroup of congenital muscular dystrophies designated α-dystroglycanopathies, because deficient O-Man glycosylation of α-dystroglycan disrupts laminin interaction with α-dystroglycan and the extracellular matrix. 28512129 3 61 theme laminin 846:852 arg1 interaction 854:864 laminin interaction 846:864 laminin interaction with α-dystroglycan and the extracellular matrix 846:913 Deficiencies in enzymes catalyzing O-Man biosynthesis, including the two human protein O-mannosyltransferases, POMT1 and POMT2, underlie a subgroup of congenital muscular dystrophies designated α-dystroglycanopathies, because deficient O-Man glycosylation of α-dystroglycan disrupts laminin interaction with α-dystroglycan and the extracellular matrix. 28512129 2 62 contain carries 360:366 arg3 residues 421:428 highly conserved residues 404:428 highly conserved residues in specific extracellular cadherin domains 404:471 We recently discovered that the cadherin superfamily carries O-linked mannose (O-Man) glycans at highly conserved residues in specific extracellular cadherin domains, and it was suggested that the function of E-cadherin was dependent on the O-Man glycans. 28512129 2 62 contain carries 360:366 arg2 glycans 393:399 O-linked mannose (O-Man) glycans 368:399 O-linked mannose (O-Man) glycans 368:399 We recently discovered that the cadherin superfamily carries O-linked mannose (O-Man) glycans at highly conserved residues in specific extracellular cadherin domains, and it was suggested that the function of E-cadherin was dependent on the O-Man glycans. 28512129 2 62 contain carries 360:366 arg1 superfamily 348:358 the cadherin superfamily 335:358 the cadherin superfamily 335:358 We recently discovered that the cadherin superfamily carries O-linked mannose (O-Man) glycans at highly conserved residues in specific extracellular cadherin domains, and it was suggested that the function of E-cadherin was dependent on the O-Man glycans. 28512129 2 63 theme mannose 377:383 arg1 glycans 393:399 O-linked mannose (O-Man) glycans 368:399 O-linked mannose (O-Man) glycans 368:399 We recently discovered that the cadherin superfamily carries O-linked mannose (O-Man) glycans at highly conserved residues in specific extracellular cadherin domains, and it was suggested that the function of E-cadherin was dependent on the O-Man glycans. 28512129 5 64 theme protocadherins 1293:1306 arg1 O-mannosylation 1260:1274 O-mannosylation 1260:1274 O-mannosylation of cadherins and protocadherins 1260:1306 Surprisingly, O-mannosylation of cadherins and protocadherins does not require POMT1 and/or POMT2 in contrast to α-dystroglycan, and moreover, the O-Man glycans on cadherins are not elongated. 28512129 3 65 theme congenital 714:723 arg1 dystrophies 734:744 congenital muscular dystrophies 714:744 congenital muscular dystrophies designated α-dystroglycanopathies 714:778 Deficiencies in enzymes catalyzing O-Man biosynthesis, including the two human protein O-mannosyltransferases, POMT1 and POMT2, underlie a subgroup of congenital muscular dystrophies designated α-dystroglycanopathies, because deficient O-Man glycosylation of α-dystroglycan disrupts laminin interaction with α-dystroglycan and the extracellular matrix. 28512129 3 66 theme human 636:640 arg1 O-mannosyltransferases 650:671 the two human protein O-mannosyltransferases 628:671 the two human protein O-mannosyltransferases 628:671 Deficiencies in enzymes catalyzing O-Man biosynthesis, including the two human protein O-mannosyltransferases, POMT1 and POMT2, underlie a subgroup of congenital muscular dystrophies designated α-dystroglycanopathies, because deficient O-Man glycosylation of α-dystroglycan disrupts laminin interaction with α-dystroglycan and the extracellular matrix. 28512129 3 66 theme human 636:640 arg1 POMT2 684:688 POMT2 684:688 POMT2 684:688 Deficiencies in enzymes catalyzing O-Man biosynthesis, including the two human protein O-mannosyltransferases, POMT1 and POMT2, underlie a subgroup of congenital muscular dystrophies designated α-dystroglycanopathies, because deficient O-Man glycosylation of α-dystroglycan disrupts laminin interaction with α-dystroglycan and the extracellular matrix. 28512129 3 66 theme human 636:640 arg1 POMT1 674:678 POMT1 674:678 POMT1 674:678 Deficiencies in enzymes catalyzing O-Man biosynthesis, including the two human protein O-mannosyltransferases, POMT1 and POMT2, underlie a subgroup of congenital muscular dystrophies designated α-dystroglycanopathies, because deficient O-Man glycosylation of α-dystroglycan disrupts laminin interaction with α-dystroglycan and the extracellular matrix. 28512129 2 67 from residues 421:428 arg1 domains 465:471 specific extracellular cadherin domains 433:471 specific extracellular cadherin domains 433:471 We recently discovered that the cadherin superfamily carries O-linked mannose (O-Man) glycans at highly conserved residues in specific extracellular cadherin domains, and it was suggested that the function of E-cadherin was dependent on the O-Man glycans. 28512129 2 68 theme O-linked 368:375 arg1 glycans 393:399 O-linked mannose (O-Man) glycans 368:399 O-linked mannose (O-Man) glycans 368:399 We recently discovered that the cadherin superfamily carries O-linked mannose (O-Man) glycans at highly conserved residues in specific extracellular cadherin domains, and it was suggested that the function of E-cadherin was dependent on the O-Man glycans. 28512129 6 69 theme mammalian 1629:1637 arg1 cells 1639:1643 mammalian cells 1629:1643 mammalian cells 1629:1643 Thus, the classical and evolutionarily conserved POMT O-mannosylation pathway is essentially dedicated to α-dystroglycan and a few other proteins, whereas a novel O-mannosylation process in mammalian cells is predicted to serve the large cadherin superfamily and other proteins. 28512129 3 70 theme extracellular 894:906 arg1 matrix 908:913 the extracellular matrix 890:913 the extracellular matrix 890:913 Deficiencies in enzymes catalyzing O-Man biosynthesis, including the two human protein O-mannosyltransferases, POMT1 and POMT2, underlie a subgroup of congenital muscular dystrophies designated α-dystroglycanopathies, because deficient O-Man glycosylation of α-dystroglycan disrupts laminin interaction with α-dystroglycan and the extracellular matrix. 28512129 4 71 theme major 1137:1141 arg1 POMGnT1 1237:1243 POMGnT1 1237:1243 POMGnT1 1237:1243 To explore the functions of O-Man glycans on cadherins and protocadherins, we used a combinatorial gene-editing strategy in multiple cell lines to evaluate the role of the two POMTs initiating O-Man glycosylation and the major enzyme elongating O-Man glycans, the protein O-mannose β-1,2-N-acetylglucosaminyltransferase, POMGnT1. 28512129 4 71 theme major 1137:1141 arg1 enzyme 1143:1148 the major enzyme elongating O-Man glycans, the protein O-mannose β-1,2-N-acetylglucosaminyltransferase, POMGnT1 1133:1243 enzyme 1143:1148 To explore the functions of O-Man glycans on cadherins and protocadherins, we used a combinatorial gene-editing strategy in multiple cell lines to evaluate the role of the two POMTs initiating O-Man glycosylation and the major enzyme elongating O-Man glycans, the protein O-mannose β-1,2-N-acetylglucosaminyltransferase, POMGnT1. 28512129 4 71 theme major 1137:1141 arg1 β-1,2-N-acetylglucosaminyltransferase 1198:1234 the protein O-mannose β-1,2-N-acetylglucosaminyltransferase 1176:1234 the protein O-mannose β-1,2-N-acetylglucosaminyltransferase 1176:1234 To explore the functions of O-Man glycans on cadherins and protocadherins, we used a combinatorial gene-editing strategy in multiple cell lines to evaluate the role of the two POMTs initiating O-Man glycosylation and the major enzyme elongating O-Man glycans, the protein O-mannose β-1,2-N-acetylglucosaminyltransferase, POMGnT1. 28512129 4 72 theme protein 1180:1186 arg1 β-1,2-N-acetylglucosaminyltransferase 1198:1234 the protein O-mannose β-1,2-N-acetylglucosaminyltransferase 1176:1234 the protein O-mannose β-1,2-N-acetylglucosaminyltransferase 1176:1234 To explore the functions of O-Man glycans on cadherins and protocadherins, we used a combinatorial gene-editing strategy in multiple cell lines to evaluate the role of the two POMTs initiating O-Man glycosylation and the major enzyme elongating O-Man glycans, the protein O-mannose β-1,2-N-acetylglucosaminyltransferase, POMGnT1. 28512129 4 72 theme protein 1180:1186 arg1 enzyme 1143:1148 the major enzyme elongating O-Man glycans, the protein O-mannose β-1,2-N-acetylglucosaminyltransferase, POMGnT1 1133:1243 enzyme 1143:1148 To explore the functions of O-Man glycans on cadherins and protocadherins, we used a combinatorial gene-editing strategy in multiple cell lines to evaluate the role of the two POMTs initiating O-Man glycosylation and the major enzyme elongating O-Man glycans, the protein O-mannose β-1,2-N-acetylglucosaminyltransferase, POMGnT1. 28512129 6 73 theme large 1671:1675 arg1 superfamily 1686:1696 the large cadherin superfamily 1667:1696 the large cadherin superfamily 1667:1696 Thus, the classical and evolutionarily conserved POMT O-mannosylation pathway is essentially dedicated to α-dystroglycan and a few other proteins, whereas a novel O-mannosylation process in mammalian cells is predicted to serve the large cadherin superfamily and other proteins. 28512129 0 74 theme protein 69:75 arg1 O-mannosyltransferases 77:98 protein O-mannosyltransferases 1 and 2 69:106 O-mannosyltransferases 77:98 Mammalian O-mannosylation of cadherins and plexins is independent of protein O-mannosyltransferases 1 and 2. 28512129 2 75 theme specific 433:440 arg1 domains 465:471 specific extracellular cadherin domains 433:471 specific extracellular cadherin domains 433:471 We recently discovered that the cadherin superfamily carries O-linked mannose (O-Man) glycans at highly conserved residues in specific extracellular cadherin domains, and it was suggested that the function of E-cadherin was dependent on the O-Man glycans. 28512129 3 76 theme protein 642:648 arg1 O-mannosyltransferases 650:671 the two human protein O-mannosyltransferases 628:671 the two human protein O-mannosyltransferases 628:671 Deficiencies in enzymes catalyzing O-Man biosynthesis, including the two human protein O-mannosyltransferases, POMT1 and POMT2, underlie a subgroup of congenital muscular dystrophies designated α-dystroglycanopathies, because deficient O-Man glycosylation of α-dystroglycan disrupts laminin interaction with α-dystroglycan and the extracellular matrix. 28512129 3 76 theme protein 642:648 arg1 POMT2 684:688 POMT2 684:688 POMT2 684:688 Deficiencies in enzymes catalyzing O-Man biosynthesis, including the two human protein O-mannosyltransferases, POMT1 and POMT2, underlie a subgroup of congenital muscular dystrophies designated α-dystroglycanopathies, because deficient O-Man glycosylation of α-dystroglycan disrupts laminin interaction with α-dystroglycan and the extracellular matrix. 28512129 3 76 theme protein 642:648 arg1 POMT1 674:678 POMT1 674:678 POMT1 674:678 Deficiencies in enzymes catalyzing O-Man biosynthesis, including the two human protein O-mannosyltransferases, POMT1 and POMT2, underlie a subgroup of congenital muscular dystrophies designated α-dystroglycanopathies, because deficient O-Man glycosylation of α-dystroglycan disrupts laminin interaction with α-dystroglycan and the extracellular matrix. 28512129 2 77 link O-linked 368:375 arg1 glycans 393:399 O-linked mannose (O-Man) glycans 368:399 O-linked mannose (O-Man) glycans 368:399 We recently discovered that the cadherin superfamily carries O-linked mannose (O-Man) glycans at highly conserved residues in specific extracellular cadherin domains, and it was suggested that the function of E-cadherin was dependent on the O-Man glycans. 28512129 6 78 theme other 1702:1706 arg1 proteins 1708:1715 other proteins 1702:1715 other proteins 1702:1715 Thus, the classical and evolutionarily conserved POMT O-mannosylation pathway is essentially dedicated to α-dystroglycan and a few other proteins, whereas a novel O-mannosylation process in mammalian cells is predicted to serve the large cadherin superfamily and other proteins. 28512129 6 79 theme O-mannosylation 1602:1616 arg1 process 1618:1624 a novel O-mannosylation process 1594:1624 a novel O-mannosylation process in mammalian cells 1594:1643 Thus, the classical and evolutionarily conserved POMT O-mannosylation pathway is essentially dedicated to α-dystroglycan and a few other proteins, whereas a novel O-mannosylation process in mammalian cells is predicted to serve the large cadherin superfamily and other proteins. 28512129 4 80 theme multiple 1040:1047 arg1 lines 1054:1058 multiple cell lines 1040:1058 multiple cell lines 1040:1058 To explore the functions of O-Man glycans on cadherins and protocadherins, we used a combinatorial gene-editing strategy in multiple cell lines to evaluate the role of the two POMTs initiating O-Man glycosylation and the major enzyme elongating O-Man glycans, the protein O-mannose β-1,2-N-acetylglucosaminyltransferase, POMGnT1. 28230759 2 0 theme ion 519:521 arg1 mode 523:526 negative ion mode 510:526 negative ion mode 510:526 In this paper, the phytochemical components of the total biflavonoids extract from S. doederleinii were studied by using high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF MS/MS) in negative ion mode, and their in vitro and in vivo anticancer effects were evaluated. 28230759 3 1 theme C-O 698:700 arg1 biflavonoids 709:720 C-O linked biflavonoids 698:720 C-O linked biflavonoids 698:720 Four types of biflavonoids from S. doederleinii, including IC3'-IIC8'', IC3'-IIC6'', IC3'-IIC3''', and C-O linked biflavonoids were examined originally using QTOF MS/MS. 28230759 6 2 theme -2,5-diphenyltertazolium 1056:1079 arg1 MTT 1090:1092 MTT 1090:1092 MTT 1090:1092 Furthermore, the 3-(4,5-Dimethyl-2-thizolyl)-2,5-diphenyltertazolium bromide (MTT) assay and xenograft model of mouse lewis lung cancer(LLC) in male C57BL/6 mice revealed favorable anticancer properties of the total biflavonoids extracts from S. doederleinii. 28230759 6 2 theme -2,5-diphenyltertazolium 1056:1079 arg1 bromide 1081:1087 the 3-(4,5-Dimethyl-2-thizolyl)-2,5-diphenyltertazolium bromide 1025:1087 the 3-(4,5-Dimethyl-2-thizolyl)-2,5-diphenyltertazolium bromide (MTT) assay 1025:1099 Furthermore, the 3-(4,5-Dimethyl-2-thizolyl)-2,5-diphenyltertazolium bromide (MTT) assay and xenograft model of mouse lewis lung cancer(LLC) in male C57BL/6 mice revealed favorable anticancer properties of the total biflavonoids extracts from S. doederleinii. 28230759 1 3 theme doederleinii 150:161 arg1 medicine 225:232 a folk antitumor herbal medicine 201:232 a folk antitumor herbal medicine in China 201:241 Selaginella doederleinii Hieron has been traditionally used as a folk antitumor herbal medicine in China. 28230759 1 3 theme doederleinii 150:161 arg1 Hieron 163:168 Selaginella doederleinii Hieron 138:168 Selaginella doederleinii Hieron 138:168 Selaginella doederleinii Hieron has been traditionally used as a folk antitumor herbal medicine in China. 28230759 2 4 theme negative 510:517 arg1 mode 523:526 negative ion mode 510:526 negative ion mode 510:526 In this paper, the phytochemical components of the total biflavonoids extract from S. doederleinii were studied by using high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF MS/MS) in negative ion mode, and their in vitro and in vivo anticancer effects were evaluated. 28230759 0 5 dep In 110:111 arg1 Vivo 113:116 Vivo 113:116 Vivo 113:116 Analysis of the Total Biflavonoids Extract from Selaginella doederleinii by HPLC-QTOF-MS and Its In Vitro and In Vivo Anticancer Effects. 28230759 2 6 from spectrometry 472:483 arg1 mode 523:526 negative ion mode 510:526 negative ion mode 510:526 In this paper, the phytochemical components of the total biflavonoids extract from S. doederleinii were studied by using high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF MS/MS) in negative ion mode, and their in vitro and in vivo anticancer effects were evaluated. 28230759 0 7 theme In 97:98 arg1 Effects 129:135 Its In Vitro and In Vivo Anticancer Effects 93:135 Its In Vitro and In Vivo Anticancer Effects 93:135 Analysis of the Total Biflavonoids Extract from Selaginella doederleinii by HPLC-QTOF-MS and Its In Vitro and In Vivo Anticancer Effects. 28230759 0 8 from Analysis 0:7 arg1 Selaginella 48:58 Selaginella 48:58 Selaginella 48:58 Analysis of the Total Biflavonoids Extract from Selaginella doederleinii by HPLC-QTOF-MS and Its In Vitro and In Vivo Anticancer Effects. 28230759 7 9 from identification 1336:1349 arg1 samples 1377:1383 herbal samples 1370:1383 herbal samples 1370:1383 The results of this work could provide useful knowledge for the identification of biflavonoids in herbal samples and further insights into the chemopreventive function of this plant. 28230759 6 10 theme male 1156:1159 arg1 mice 1169:1172 male C57BL/6 mice 1156:1172 male C57BL/6 mice 1156:1172 Furthermore, the 3-(4,5-Dimethyl-2-thizolyl)-2,5-diphenyltertazolium bromide (MTT) assay and xenograft model of mouse lewis lung cancer(LLC) in male C57BL/6 mice revealed favorable anticancer properties of the total biflavonoids extracts from S. doederleinii. 28230759 7 11 theme plant 1448:1452 arg1 function 1431:1438 the chemopreventive function 1411:1438 the chemopreventive function of this plant 1411:1452 The results of this work could provide useful knowledge for the identification of biflavonoids in herbal samples and further insights into the chemopreventive function of this plant. 28230759 6 12 from properties 1204:1213 arg1 doederleinii 1258:1269 S. doederleinii 1255:1269 S. doederleinii 1255:1269 Furthermore, the 3-(4,5-Dimethyl-2-thizolyl)-2,5-diphenyltertazolium bromide (MTT) assay and xenograft model of mouse lewis lung cancer(LLC) in male C57BL/6 mice revealed favorable anticancer properties of the total biflavonoids extracts from S. doederleinii. 28230759 2 13 theme in 539:540 arg1 effects 571:577 their in vitro and in vivo anticancer effects 533:577 their in vitro and in vivo anticancer effects 533:577 In this paper, the phytochemical components of the total biflavonoids extract from S. doederleinii were studied by using high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF MS/MS) in negative ion mode, and their in vitro and in vivo anticancer effects were evaluated. 28230759 0 14 from Selaginella 48:58 arg1 Extract 35:41 the Total Biflavonoids Extract 12:41 the Total Biflavonoids Extract from Selaginella doederleinii 12:71 Analysis of the Total Biflavonoids Extract from Selaginella doederleinii by HPLC-QTOF-MS and Its In Vitro and In Vivo Anticancer Effects. 28230759 0 14 from Selaginella 48:58 arg1 Analysis 0:7 Analysis 0:7 Analysis of the Total Biflavonoids Extract from Selaginella doederleinii by HPLC-QTOF-MS and Its In Vitro and In Vivo Anticancer Effects. 0:136 Analysis of the Total Biflavonoids Extract from Selaginella doederleinii by HPLC-QTOF-MS and Its In Vitro and In Vivo Anticancer Effects. 28230759 2 15 from doederleinii 330:341 arg1 extract 314:320 the total biflavonoids extract 291:320 the total biflavonoids extract from S. doederleinii 291:341 In this paper, the phytochemical components of the total biflavonoids extract from S. doederleinii were studied by using high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF MS/MS) in negative ion mode, and their in vitro and in vivo anticancer effects were evaluated. 28230759 2 15 from doederleinii 330:341 arg1 components 277:286 the phytochemical components 259:286 the phytochemical components of the total biflavonoids extract from S. doederleinii 259:341 In this paper, the phytochemical components of the total biflavonoids extract from S. doederleinii were studied by using high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF MS/MS) in negative ion mode, and their in vitro and in vivo anticancer effects were evaluated. 28230759 2 16 theme phytochemical 263:275 arg1 components 277:286 the phytochemical components 259:286 the phytochemical components of the total biflavonoids extract from S. doederleinii 259:341 In this paper, the phytochemical components of the total biflavonoids extract from S. doederleinii were studied by using high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF MS/MS) in negative ion mode, and their in vitro and in vivo anticancer effects were evaluated. 28230759 3 17 link linked 702:707 arg1 biflavonoids 709:720 C-O linked biflavonoids 698:720 C-O linked biflavonoids 698:720 Four types of biflavonoids from S. doederleinii, including IC3'-IIC8'', IC3'-IIC6'', IC3'-IIC3''', and C-O linked biflavonoids were examined originally using QTOF MS/MS. 28230759 6 18 theme mouse 1124:1128 arg1 LLC 1148:1150 LLC 1148:1150 LLC 1148:1150 Furthermore, the 3-(4,5-Dimethyl-2-thizolyl)-2,5-diphenyltertazolium bromide (MTT) assay and xenograft model of mouse lewis lung cancer(LLC) in male C57BL/6 mice revealed favorable anticancer properties of the total biflavonoids extracts from S. doederleinii. 28230759 6 18 theme mouse 1124:1128 arg1 cancer 1141:1146 mouse lewis lung cancer 1124:1146 mouse lewis lung cancer(LLC) 1124:1151 Furthermore, the 3-(4,5-Dimethyl-2-thizolyl)-2,5-diphenyltertazolium bromide (MTT) assay and xenograft model of mouse lewis lung cancer(LLC) in male C57BL/6 mice revealed favorable anticancer properties of the total biflavonoids extracts from S. doederleinii. 28230759 4 19 theme first 849:853 arg1 time 855:858 the first time 845:858 the first time 845:858 The fragmentation behavior of IC3'-IIC3''' linked biflavonoids was reported for the first time. 28230759 6 20 theme xenograft 1105:1113 arg1 model 1115:1119 xenograft model 1105:1119 xenograft model 1105:1119 Furthermore, the 3-(4,5-Dimethyl-2-thizolyl)-2,5-diphenyltertazolium bromide (MTT) assay and xenograft model of mouse lewis lung cancer(LLC) in male C57BL/6 mice revealed favorable anticancer properties of the total biflavonoids extracts from S. doederleinii. 28230759 0 21 dep In 97:98 arg1 Vitro 100:104 Vitro 100:104 Vitro 100:104 Analysis of the Total Biflavonoids Extract from Selaginella doederleinii by HPLC-QTOF-MS and Its In Vitro and In Vivo Anticancer Effects. 28230759 7 22 from biflavonoids 1354:1365 arg1 samples 1377:1383 herbal samples 1370:1383 herbal samples 1370:1383 The results of this work could provide useful knowledge for the identification of biflavonoids in herbal samples and further insights into the chemopreventive function of this plant. 28230759 4 23 theme biflavonoids 709:720 arg1 behavior 783:790 The fragmentation behavior 765:790 765:720 The fragmentation behavior of IC3'-IIC3''' linked biflavonoids was reported for the first time. 28230759 6 24 from doederleinii 1258:1269 arg1 properties 1204:1213 favorable anticancer properties 1183:1213 favorable anticancer properties of the total biflavonoids extracts from S. doederleinii 1183:1269 Furthermore, the 3-(4,5-Dimethyl-2-thizolyl)-2,5-diphenyltertazolium bromide (MTT) assay and xenograft model of mouse lewis lung cancer(LLC) in male C57BL/6 mice revealed favorable anticancer properties of the total biflavonoids extracts from S. doederleinii. 28230759 6 24 from doederleinii 1258:1269 arg1 extracts 1241:1248 the total biflavonoids extracts 1218:1248 the total biflavonoids extracts from S. doederleinii 1218:1269 Furthermore, the 3-(4,5-Dimethyl-2-thizolyl)-2,5-diphenyltertazolium bromide (MTT) assay and xenograft model of mouse lewis lung cancer(LLC) in male C57BL/6 mice revealed favorable anticancer properties of the total biflavonoids extracts from S. doederleinii. 28230759 3 25 theme linked 702:707 arg1 biflavonoids 709:720 C-O linked biflavonoids 698:720 C-O linked biflavonoids 698:720 Four types of biflavonoids from S. doederleinii, including IC3'-IIC8'', IC3'-IIC6'', IC3'-IIC3''', and C-O linked biflavonoids were examined originally using QTOF MS/MS. 28230759 7 26 theme useful 1311:1316 arg1 knowledge 1318:1326 useful knowledge 1311:1326 useful knowledge for the identification of biflavonoids in herbal samples 1311:1383 The results of this work could provide useful knowledge for the identification of biflavonoids in herbal samples and further insights into the chemopreventive function of this plant. 28230759 4 27 theme fragmentation 769:781 arg1 behavior 783:790 The fragmentation behavior 765:790 765:720 The fragmentation behavior of IC3'-IIC3''' linked biflavonoids was reported for the first time. 28230759 3 28 from doederleinii 630:641 arg1 biflavonoids 609:620 biflavonoids 609:620 biflavonoids 609:620 Four types of biflavonoids from S. doederleinii, including IC3'-IIC8'', IC3'-IIC6'', IC3'-IIC3''', and C-O linked biflavonoids were examined originally using QTOF MS/MS. 28230759 3 28 from doederleinii 630:641 arg1 types 600:604 Four types 595:604 Four types of biflavonoids from S. doederleinii, including IC3'-IIC8'', IC3'-IIC6'', IC3'-IIC3''', and C-O linked biflavonoids 595:720 Four types of biflavonoids from S. doederleinii, including IC3'-IIC8'', IC3'-IIC6'', IC3'-IIC3''', and C-O linked biflavonoids were examined originally using QTOF MS/MS. 28230759 7 29 theme chemopreventive 1415:1429 arg1 function 1431:1438 the chemopreventive function 1411:1438 the chemopreventive function of this plant 1411:1452 The results of this work could provide useful knowledge for the identification of biflavonoids in herbal samples and further insights into the chemopreventive function of this plant. 28230759 7 30 theme further 1389:1395 arg1 insights 1397:1404 further insights 1389:1404 further insights into the chemopreventive function of this plant 1389:1452 The results of this work could provide useful knowledge for the identification of biflavonoids in herbal samples and further insights into the chemopreventive function of this plant. 28230759 7 31 theme work 1292:1295 arg1 results 1276:1282 The results 1272:1282 The results of this work 1272:1295 The results of this work could provide useful knowledge for the identification of biflavonoids in herbal samples and further insights into the chemopreventive function of this plant. 28230759 2 32 theme biflavonoids 301:312 arg1 extract 314:320 the total biflavonoids extract 291:320 the total biflavonoids extract from S. doederleinii 291:341 In this paper, the phytochemical components of the total biflavonoids extract from S. doederleinii were studied by using high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF MS/MS) in negative ion mode, and their in vitro and in vivo anticancer effects were evaluated. 28230759 2 33 theme liquid 382:387 arg1 chromatography 389:402 high-performance liquid chromatography 365:402 high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF MS/MS) in negative ion mode 365:526 In this paper, the phytochemical components of the total biflavonoids extract from S. doederleinii were studied by using high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF MS/MS) in negative ion mode, and their in vitro and in vivo anticancer effects were evaluated. 28230759 3 34 theme QTOF 753:756 arg1 MS/MS 758:762 QTOF MS/MS 753:762 QTOF MS/MS 753:762 Four types of biflavonoids from S. doederleinii, including IC3'-IIC8'', IC3'-IIC6'', IC3'-IIC3''', and C-O linked biflavonoids were examined originally using QTOF MS/MS. 28230759 2 35 theme total 295:299 arg1 extract 314:320 the total biflavonoids extract 291:320 the total biflavonoids extract from S. doederleinii 291:341 In this paper, the phytochemical components of the total biflavonoids extract from S. doederleinii were studied by using high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF MS/MS) in negative ion mode, and their in vitro and in vivo anticancer effects were evaluated. 28230759 7 36 theme herbal 1370:1375 arg1 samples 1377:1383 herbal samples 1370:1383 herbal samples 1370:1383 The results of this work could provide useful knowledge for the identification of biflavonoids in herbal samples and further insights into the chemopreventive function of this plant. 28230759 2 37 theme high-performance 365:380 arg1 chromatography 389:402 high-performance liquid chromatography 365:402 high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF MS/MS) in negative ion mode 365:526 In this paper, the phytochemical components of the total biflavonoids extract from S. doederleinii were studied by using high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF MS/MS) in negative ion mode, and their in vitro and in vivo anticancer effects were evaluated. 28230759 2 38 theme mass 467:470 arg1 spectrometry 472:483 electrospray ionization quadrupole time-of-flight mass spectrometry 417:483 electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF MS/MS) in negative ion mode 417:526 In this paper, the phytochemical components of the total biflavonoids extract from S. doederleinii were studied by using high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF MS/MS) in negative ion mode, and their in vitro and in vivo anticancer effects were evaluated. 28230759 2 38 theme mass 467:470 arg1 MS/MS 500:504 HPLC-ESI-QTOF MS/MS 486:504 HPLC-ESI-QTOF MS/MS 486:504 In this paper, the phytochemical components of the total biflavonoids extract from S. doederleinii were studied by using high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF MS/MS) in negative ion mode, and their in vitro and in vivo anticancer effects were evaluated. 28230759 6 39 theme anticancer 1193:1202 arg1 properties 1204:1213 favorable anticancer properties 1183:1213 favorable anticancer properties of the total biflavonoids extracts from S. doederleinii 1183:1269 Furthermore, the 3-(4,5-Dimethyl-2-thizolyl)-2,5-diphenyltertazolium bromide (MTT) assay and xenograft model of mouse lewis lung cancer(LLC) in male C57BL/6 mice revealed favorable anticancer properties of the total biflavonoids extracts from S. doederleinii. 28230759 2 40 theme anticancer 560:569 arg1 effects 571:577 their in vitro and in vivo anticancer effects 533:577 their in vitro and in vivo anticancer effects 533:577 In this paper, the phytochemical components of the total biflavonoids extract from S. doederleinii were studied by using high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF MS/MS) in negative ion mode, and their in vitro and in vivo anticancer effects were evaluated. 28230759 3 41 from types 600:604 arg1 doederleinii 630:641 S. doederleinii 627:641 S. doederleinii 627:641 Four types of biflavonoids from S. doederleinii, including IC3'-IIC8'', IC3'-IIC6'', IC3'-IIC3''', and C-O linked biflavonoids were examined originally using QTOF MS/MS. 28230759 2 42 theme quadrupole 441:450 arg1 spectrometry 472:483 electrospray ionization quadrupole time-of-flight mass spectrometry 417:483 electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF MS/MS) in negative ion mode 417:526 In this paper, the phytochemical components of the total biflavonoids extract from S. doederleinii were studied by using high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF MS/MS) in negative ion mode, and their in vitro and in vivo anticancer effects were evaluated. 28230759 2 42 theme quadrupole 441:450 arg1 MS/MS 500:504 HPLC-ESI-QTOF MS/MS 486:504 HPLC-ESI-QTOF MS/MS 486:504 In this paper, the phytochemical components of the total biflavonoids extract from S. doederleinii were studied by using high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF MS/MS) in negative ion mode, and their in vitro and in vivo anticancer effects were evaluated. 28230759 2 43 theme time-of-flight 452:465 arg1 spectrometry 472:483 electrospray ionization quadrupole time-of-flight mass spectrometry 417:483 electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF MS/MS) in negative ion mode 417:526 In this paper, the phytochemical components of the total biflavonoids extract from S. doederleinii were studied by using high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF MS/MS) in negative ion mode, and their in vitro and in vivo anticancer effects were evaluated. 28230759 2 43 theme time-of-flight 452:465 arg1 MS/MS 500:504 HPLC-ESI-QTOF MS/MS 486:504 HPLC-ESI-QTOF MS/MS 486:504 In this paper, the phytochemical components of the total biflavonoids extract from S. doederleinii were studied by using high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF MS/MS) in negative ion mode, and their in vitro and in vivo anticancer effects were evaluated. 28230759 0 44 theme In 110:111 arg1 Effects 129:135 Its In Vitro and In Vivo Anticancer Effects 93:135 Its In Vitro and In Vivo Anticancer Effects 93:135 Analysis of the Total Biflavonoids Extract from Selaginella doederleinii by HPLC-QTOF-MS and Its In Vitro and In Vivo Anticancer Effects. 28230759 2 45 theme ionization 430:439 arg1 spectrometry 472:483 electrospray ionization quadrupole time-of-flight mass spectrometry 417:483 electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF MS/MS) in negative ion mode 417:526 In this paper, the phytochemical components of the total biflavonoids extract from S. doederleinii were studied by using high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF MS/MS) in negative ion mode, and their in vitro and in vivo anticancer effects were evaluated. 28230759 2 45 theme ionization 430:439 arg1 MS/MS 500:504 HPLC-ESI-QTOF MS/MS 486:504 HPLC-ESI-QTOF MS/MS 486:504 In this paper, the phytochemical components of the total biflavonoids extract from S. doederleinii were studied by using high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF MS/MS) in negative ion mode, and their in vitro and in vivo anticancer effects were evaluated. 28230759 0 46 theme Extract 35:41 arg1 Analysis 0:7 Analysis 0:7 Analysis of the Total Biflavonoids Extract from Selaginella doederleinii by HPLC-QTOF-MS and Its In Vitro and In Vivo Anticancer Effects. 0:136 Analysis of the Total Biflavonoids Extract from Selaginella doederleinii by HPLC-QTOF-MS and Its In Vitro and In Vivo Anticancer Effects. 28230759 2 47 theme in 552:553 arg1 effects 571:577 their in vitro and in vivo anticancer effects 533:577 their in vitro and in vivo anticancer effects 533:577 In this paper, the phytochemical components of the total biflavonoids extract from S. doederleinii were studied by using high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF MS/MS) in negative ion mode, and their in vitro and in vivo anticancer effects were evaluated. 28230759 2 48 theme electrospray 417:428 arg1 spectrometry 472:483 electrospray ionization quadrupole time-of-flight mass spectrometry 417:483 electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF MS/MS) in negative ion mode 417:526 In this paper, the phytochemical components of the total biflavonoids extract from S. doederleinii were studied by using high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF MS/MS) in negative ion mode, and their in vitro and in vivo anticancer effects were evaluated. 28230759 2 48 theme electrospray 417:428 arg1 MS/MS 500:504 HPLC-ESI-QTOF MS/MS 486:504 HPLC-ESI-QTOF MS/MS 486:504 In this paper, the phytochemical components of the total biflavonoids extract from S. doederleinii were studied by using high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF MS/MS) in negative ion mode, and their in vitro and in vivo anticancer effects were evaluated. 28230759 6 49 theme extracts 1241:1248 arg1 properties 1204:1213 favorable anticancer properties 1183:1213 favorable anticancer properties of the total biflavonoids extracts from S. doederleinii 1183:1269 Furthermore, the 3-(4,5-Dimethyl-2-thizolyl)-2,5-diphenyltertazolium bromide (MTT) assay and xenograft model of mouse lewis lung cancer(LLC) in male C57BL/6 mice revealed favorable anticancer properties of the total biflavonoids extracts from S. doederleinii. 28230759 1 50 theme folk 203:206 arg1 medicine 225:232 a folk antitumor herbal medicine 201:232 a folk antitumor herbal medicine in China 201:241 Selaginella doederleinii Hieron has been traditionally used as a folk antitumor herbal medicine in China. 28230759 1 50 theme folk 203:206 arg1 Hieron 163:168 Selaginella doederleinii Hieron 138:168 Selaginella doederleinii Hieron 138:168 Selaginella doederleinii Hieron has been traditionally used as a folk antitumor herbal medicine in China. 28230759 0 51 theme Biflavonoids 22:33 arg1 Extract 35:41 the Total Biflavonoids Extract 12:41 the Total Biflavonoids Extract from Selaginella doederleinii 12:71 Analysis of the Total Biflavonoids Extract from Selaginella doederleinii by HPLC-QTOF-MS and Its In Vitro and In Vivo Anticancer Effects. 28230759 0 52 theme Anticancer 118:127 arg1 Effects 129:135 Its In Vitro and In Vivo Anticancer Effects 93:135 Its In Vitro and In Vivo Anticancer Effects 93:135 Analysis of the Total Biflavonoids Extract from Selaginella doederleinii by HPLC-QTOF-MS and Its In Vitro and In Vivo Anticancer Effects. 28230759 6 53 from model 1115:1119 arg1 mice 1169:1172 male C57BL/6 mice 1156:1172 male C57BL/6 mice 1156:1172 Furthermore, the 3-(4,5-Dimethyl-2-thizolyl)-2,5-diphenyltertazolium bromide (MTT) assay and xenograft model of mouse lewis lung cancer(LLC) in male C57BL/6 mice revealed favorable anticancer properties of the total biflavonoids extracts from S. doederleinii. 28230759 0 54 theme Total 16:20 arg1 Extract 35:41 the Total Biflavonoids Extract 12:41 the Total Biflavonoids Extract from Selaginella doederleinii 12:71 Analysis of the Total Biflavonoids Extract from Selaginella doederleinii by HPLC-QTOF-MS and Its In Vitro and In Vivo Anticancer Effects. 28230759 1 55 theme antitumor 208:216 arg1 medicine 225:232 a folk antitumor herbal medicine 201:232 a folk antitumor herbal medicine in China 201:241 Selaginella doederleinii Hieron has been traditionally used as a folk antitumor herbal medicine in China. 28230759 1 55 theme antitumor 208:216 arg1 Hieron 163:168 Selaginella doederleinii Hieron 138:168 Selaginella doederleinii Hieron 138:168 Selaginella doederleinii Hieron has been traditionally used as a folk antitumor herbal medicine in China. 28230759 2 56 dep in 552:553 arg1 vivo 555:558 vivo 555:558 vivo 555:558 In this paper, the phytochemical components of the total biflavonoids extract from S. doederleinii were studied by using high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF MS/MS) in negative ion mode, and their in vitro and in vivo anticancer effects were evaluated. 28230759 6 57 theme total 1222:1226 arg1 extracts 1241:1248 the total biflavonoids extracts 1218:1248 the total biflavonoids extracts from S. doederleinii 1218:1269 Furthermore, the 3-(4,5-Dimethyl-2-thizolyl)-2,5-diphenyltertazolium bromide (MTT) assay and xenograft model of mouse lewis lung cancer(LLC) in male C57BL/6 mice revealed favorable anticancer properties of the total biflavonoids extracts from S. doederleinii. 28230759 6 58 theme cancer 1141:1146 arg1 model 1115:1119 xenograft model 1105:1119 xenograft model 1105:1119 Furthermore, the 3-(4,5-Dimethyl-2-thizolyl)-2,5-diphenyltertazolium bromide (MTT) assay and xenograft model of mouse lewis lung cancer(LLC) in male C57BL/6 mice revealed favorable anticancer properties of the total biflavonoids extracts from S. doederleinii. 28230759 6 58 theme cancer 1141:1146 arg1 assay 1095:1099 the 3-(4,5-Dimethyl-2-thizolyl)-2,5-diphenyltertazolium bromide (MTT) assay 1025:1099 the 3-(4,5-Dimethyl-2-thizolyl)-2,5-diphenyltertazolium bromide (MTT) assay 1025:1099 Furthermore, the 3-(4,5-Dimethyl-2-thizolyl)-2,5-diphenyltertazolium bromide (MTT) assay and xenograft model of mouse lewis lung cancer(LLC) in male C57BL/6 mice revealed favorable anticancer properties of the total biflavonoids extracts from S. doederleinii. 28230759 2 59 theme HPLC-ESI-QTOF 486:498 arg1 spectrometry 472:483 electrospray ionization quadrupole time-of-flight mass spectrometry 417:483 electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF MS/MS) in negative ion mode 417:526 In this paper, the phytochemical components of the total biflavonoids extract from S. doederleinii were studied by using high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF MS/MS) in negative ion mode, and their in vitro and in vivo anticancer effects were evaluated. 28230759 2 59 theme HPLC-ESI-QTOF 486:498 arg1 MS/MS 500:504 HPLC-ESI-QTOF MS/MS 486:504 HPLC-ESI-QTOF MS/MS 486:504 In this paper, the phytochemical components of the total biflavonoids extract from S. doederleinii were studied by using high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF MS/MS) in negative ion mode, and their in vitro and in vivo anticancer effects were evaluated. 28230759 6 60 theme biflavonoids 1228:1239 arg1 extracts 1241:1248 the total biflavonoids extracts 1218:1248 the total biflavonoids extracts from S. doederleinii 1218:1269 Furthermore, the 3-(4,5-Dimethyl-2-thizolyl)-2,5-diphenyltertazolium bromide (MTT) assay and xenograft model of mouse lewis lung cancer(LLC) in male C57BL/6 mice revealed favorable anticancer properties of the total biflavonoids extracts from S. doederleinii. 28230759 6 61 theme lung 1136:1139 arg1 LLC 1148:1150 LLC 1148:1150 LLC 1148:1150 Furthermore, the 3-(4,5-Dimethyl-2-thizolyl)-2,5-diphenyltertazolium bromide (MTT) assay and xenograft model of mouse lewis lung cancer(LLC) in male C57BL/6 mice revealed favorable anticancer properties of the total biflavonoids extracts from S. doederleinii. 28230759 6 61 theme lung 1136:1139 arg1 cancer 1141:1146 mouse lewis lung cancer 1124:1146 mouse lewis lung cancer(LLC) 1124:1151 Furthermore, the 3-(4,5-Dimethyl-2-thizolyl)-2,5-diphenyltertazolium bromide (MTT) assay and xenograft model of mouse lewis lung cancer(LLC) in male C57BL/6 mice revealed favorable anticancer properties of the total biflavonoids extracts from S. doederleinii. 28230759 7 62 theme biflavonoids 1354:1365 arg1 identification 1336:1349 the identification 1332:1349 the identification of biflavonoids in herbal samples 1332:1383 The results of this work could provide useful knowledge for the identification of biflavonoids in herbal samples and further insights into the chemopreventive function of this plant. 28230759 5 63 theme first 1000:1004 arg1 time 1006:1009 the first time 996:1009 the first time 996:1009 A total of twenty biflavonoids were identified or tentatively characterized and eight biflavonoids were found from S. doederleinii for the first time. 28230759 1 64 used used 193:196 arg2 Hieron 163:168 Selaginella doederleinii Hieron 138:168 Selaginella doederleinii Hieron 138:168 Selaginella doederleinii Hieron has been traditionally used as a folk antitumor herbal medicine in China. 28230759 1 64 used used 193:196 arg2 medicine 225:232 a folk antitumor herbal medicine 201:232 a folk antitumor herbal medicine in China 201:241 Selaginella doederleinii Hieron has been traditionally used as a folk antitumor herbal medicine in China. 28230759 3 65 theme biflavonoids 609:620 arg1 types 600:604 Four types 595:604 Four types of biflavonoids from S. doederleinii, including IC3'-IIC8'', IC3'-IIC6'', IC3'-IIC3''', and C-O linked biflavonoids 595:720 Four types of biflavonoids from S. doederleinii, including IC3'-IIC8'', IC3'-IIC6'', IC3'-IIC3''', and C-O linked biflavonoids were examined originally using QTOF MS/MS. 28230759 6 66 theme lewis 1130:1134 arg1 LLC 1148:1150 LLC 1148:1150 LLC 1148:1150 Furthermore, the 3-(4,5-Dimethyl-2-thizolyl)-2,5-diphenyltertazolium bromide (MTT) assay and xenograft model of mouse lewis lung cancer(LLC) in male C57BL/6 mice revealed favorable anticancer properties of the total biflavonoids extracts from S. doederleinii. 28230759 6 66 theme lewis 1130:1134 arg1 cancer 1141:1146 mouse lewis lung cancer 1124:1146 mouse lewis lung cancer(LLC) 1124:1151 Furthermore, the 3-(4,5-Dimethyl-2-thizolyl)-2,5-diphenyltertazolium bromide (MTT) assay and xenograft model of mouse lewis lung cancer(LLC) in male C57BL/6 mice revealed favorable anticancer properties of the total biflavonoids extracts from S. doederleinii. 28230759 1 67 theme herbal 218:223 arg1 medicine 225:232 a folk antitumor herbal medicine 201:232 a folk antitumor herbal medicine in China 201:241 Selaginella doederleinii Hieron has been traditionally used as a folk antitumor herbal medicine in China. 28230759 1 67 theme herbal 218:223 arg1 Hieron 163:168 Selaginella doederleinii Hieron 138:168 Selaginella doederleinii Hieron 138:168 Selaginella doederleinii Hieron has been traditionally used as a folk antitumor herbal medicine in China. 28230759 1 68 from medicine 225:232 arg1 China 237:241 China 237:241 China 237:241 Selaginella doederleinii Hieron has been traditionally used as a folk antitumor herbal medicine in China. 28230759 7 69 from samples 1377:1383 arg1 identification 1336:1349 the identification 1332:1349 the identification of biflavonoids in herbal samples 1332:1383 The results of this work could provide useful knowledge for the identification of biflavonoids in herbal samples and further insights into the chemopreventive function of this plant. 28230759 6 70 theme bromide 1081:1087 arg1 assay 1095:1099 the 3-(4,5-Dimethyl-2-thizolyl)-2,5-diphenyltertazolium bromide (MTT) assay 1025:1099 the 3-(4,5-Dimethyl-2-thizolyl)-2,5-diphenyltertazolium bromide (MTT) assay 1025:1099 Furthermore, the 3-(4,5-Dimethyl-2-thizolyl)-2,5-diphenyltertazolium bromide (MTT) assay and xenograft model of mouse lewis lung cancer(LLC) in male C57BL/6 mice revealed favorable anticancer properties of the total biflavonoids extracts from S. doederleinii. 28230759 2 71 dep in 539:540 arg1 vitro 542:546 vitro 542:546 vitro 542:546 In this paper, the phytochemical components of the total biflavonoids extract from S. doederleinii were studied by using high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF MS/MS) in negative ion mode, and their in vitro and in vivo anticancer effects were evaluated. 28230759 2 72 theme extract 314:320 arg1 components 277:286 the phytochemical components 259:286 the phytochemical components of the total biflavonoids extract from S. doederleinii 259:341 In this paper, the phytochemical components of the total biflavonoids extract from S. doederleinii were studied by using high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF MS/MS) in negative ion mode, and their in vitro and in vivo anticancer effects were evaluated. 28230759 2 73 from components 277:286 arg1 doederleinii 330:341 S. doederleinii 327:341 S. doederleinii 327:341 In this paper, the phytochemical components of the total biflavonoids extract from S. doederleinii were studied by using high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF MS/MS) in negative ion mode, and their in vitro and in vivo anticancer effects were evaluated. 28230759 6 74 theme 4,5-Dimethyl-2-thizolyl 1032:1054 arg1 MTT 1090:1092 MTT 1090:1092 MTT 1090:1092 Furthermore, the 3-(4,5-Dimethyl-2-thizolyl)-2,5-diphenyltertazolium bromide (MTT) assay and xenograft model of mouse lewis lung cancer(LLC) in male C57BL/6 mice revealed favorable anticancer properties of the total biflavonoids extracts from S. doederleinii. 28230759 6 74 theme 4,5-Dimethyl-2-thizolyl 1032:1054 arg1 bromide 1081:1087 the 3-(4,5-Dimethyl-2-thizolyl)-2,5-diphenyltertazolium bromide 1025:1087 the 3-(4,5-Dimethyl-2-thizolyl)-2,5-diphenyltertazolium bromide (MTT) assay 1025:1099 Furthermore, the 3-(4,5-Dimethyl-2-thizolyl)-2,5-diphenyltertazolium bromide (MTT) assay and xenograft model of mouse lewis lung cancer(LLC) in male C57BL/6 mice revealed favorable anticancer properties of the total biflavonoids extracts from S. doederleinii. 28230759 4 75 theme linked 702:707 arg1 biflavonoids 709:720 -1:720 -1:720 The fragmentation behavior of IC3'-IIC3''' linked biflavonoids was reported for the first time. 28230759 4 76 link linked 702:707 arg1 biflavonoids 709:720 -1:720 -1:720 The fragmentation behavior of IC3'-IIC3''' linked biflavonoids was reported for the first time. 28230759 5 77 theme biflavonoids 879:890 arg1 total 863:867 A total 861:867 A total of twenty biflavonoids 861:890 A total of twenty biflavonoids were identified or tentatively characterized and eight biflavonoids were found from S. doederleinii for the first time. 28230759 6 78 theme C57BL/6 1161:1167 arg1 mice 1169:1172 male C57BL/6 mice 1156:1172 male C57BL/6 mice 1156:1172 Furthermore, the 3-(4,5-Dimethyl-2-thizolyl)-2,5-diphenyltertazolium bromide (MTT) assay and xenograft model of mouse lewis lung cancer(LLC) in male C57BL/6 mice revealed favorable anticancer properties of the total biflavonoids extracts from S. doederleinii. 28230759 6 79 theme favorable 1183:1191 arg1 properties 1204:1213 favorable anticancer properties 1183:1213 favorable anticancer properties of the total biflavonoids extracts from S. doederleinii 1183:1269 Furthermore, the 3-(4,5-Dimethyl-2-thizolyl)-2,5-diphenyltertazolium bromide (MTT) assay and xenograft model of mouse lewis lung cancer(LLC) in male C57BL/6 mice revealed favorable anticancer properties of the total biflavonoids extracts from S. doederleinii. 28230759 1 80 theme Selaginella 138:148 arg1 medicine 225:232 a folk antitumor herbal medicine 201:232 a folk antitumor herbal medicine in China 201:241 Selaginella doederleinii Hieron has been traditionally used as a folk antitumor herbal medicine in China. 28230759 1 80 theme Selaginella 138:148 arg1 Hieron 163:168 Selaginella doederleinii Hieron 138:168 Selaginella doederleinii Hieron 138:168 Selaginella doederleinii Hieron has been traditionally used as a folk antitumor herbal medicine in China. 28230759 6 81 from assay 1095:1099 arg1 mice 1169:1172 male C57BL/6 mice 1156:1172 male C57BL/6 mice 1156:1172 Furthermore, the 3-(4,5-Dimethyl-2-thizolyl)-2,5-diphenyltertazolium bromide (MTT) assay and xenograft model of mouse lewis lung cancer(LLC) in male C57BL/6 mice revealed favorable anticancer properties of the total biflavonoids extracts from S. doederleinii. 27496881 3 0 theme 6-mo-old 672:679 arg1 mice 681:684 6-mo-old mice 672:684 6-mo-old mice 672:684 Following a longitudinal study design, we used 3- and 6-mo-old mice, untreated or treated for 3 mo with ivabradine or metoprolol. 27496881 4 1 theme 13C-labeled 831:841 arg1 substrates 843:852 13C-labeled substrates 831:852 13C-labeled substrates 831:852 Cardiac function was evaluated in vivo and ex vivo in working hearts perfused with 13C-labeled substrates to assess substrate fluxes through energy metabolic pathways. 27496881 5 2 dep impaired 1012:1019 arg1 < 1024:1024 P < 0.001 1022:1030 P < 0.001 1022:1030 Compared with 3-mo-old, 6-mo-old dyslipidemic mice had similar cardiac hemodynamics in vivo but impaired (P < 0.001) contractile function (aortic flow: -45%; cardiac output: -34%; stroke volume: -35%) and glycolysis (-24%) ex vivo. 27496881 1 3 theme contradictory 242:254 arg1 results 256:262 contradictory results 242:262 contradictory results 242:262 While heart rate reduction (HRR) is a target for the management of patients with heart disease, contradictory results were reported using ivabradine, which selectively inhibits the pacemaker If current, vs. β-blockers like metoprolol. 27496881 4 4 theme working 802:808 arg1 hearts 810:815 working hearts 802:815 working hearts perfused with 13C-labeled substrates to assess substrate fluxes through energy metabolic pathways 802:913 Cardiac function was evaluated in vivo and ex vivo in working hearts perfused with 13C-labeled substrates to assess substrate fluxes through energy metabolic pathways. 27496881 8 5 theme alterations 1835:1845 arg1 implication 1820:1830 the implication 1816:1830 the implication of alterations in cardiac glucose metabolism and signaling linked to disease progression in our mouse model 1816:1938 Collectively, our results emphasize the implication of alterations in cardiac glucose metabolism and signaling linked to disease progression in our mouse model. 27496881 8 6 theme cardiac 1850:1856 arg1 metabolism 1866:1875 cardiac glucose metabolism 1850:1875 cardiac glucose metabolism 1850:1875 Collectively, our results emphasize the implication of alterations in cardiac glucose metabolism and signaling linked to disease progression in our mouse model. 27496881 7 7 theme proteins 1554:1561 arg1 level 1545:1549 the total tissue level 1528:1549 the total tissue level of proteins modified by O-linked N-acetylglucosamine (O-GlcNAc) 1528:1613 Further analyses highlighted additional significant cardiac alterations with disease progression, namely in the total tissue level of proteins modified by O-linked N-acetylglucosamine (O-GlcNAc), whose formation is governed by glucose metabolism via the hexosamine biosynthetic pathway, which showed a similar pattern with ivabradine vs. metoprolol treatment. 27496881 4 8 theme metabolic 896:904 arg1 pathways 906:913 energy metabolic pathways 889:913 energy metabolic pathways 889:913 Cardiac function was evaluated in vivo and ex vivo in working hearts perfused with 13C-labeled substrates to assess substrate fluxes through energy metabolic pathways. 27496881 0 9 theme dyslipidemia 132:143 arg1 model 123:127 a mouse model 115:127 a mouse model of dyslipidemia 115:143 Ivabradine and metoprolol differentially affect cardiac glucose metabolism despite similar heart rate reduction in a mouse model of dyslipidemia. 27496881 5 10 theme contractile 1033:1043 arg1 function 1045:1052 contractile function 1033:1052 contractile function (aortic flow: -45%; cardiac output: -34%; stroke volume: -35%) 1033:1115 Compared with 3-mo-old, 6-mo-old dyslipidemic mice had similar cardiac hemodynamics in vivo but impaired (P < 0.001) contractile function (aortic flow: -45%; cardiac output: -34%; stroke volume: -35%) and glycolysis (-24%) ex vivo. 27496881 2 11 theme mouse 570:574 arg1 model 576:580 a mouse model 568:580 a mouse model of dyslipidemia (hApoB+/+;LDLR-/-) 568:615 This study aimed at testing whether similar HRR with ivabradine vs. metoprolol differentially modulates cardiac energy substrate metabolism, a factor determinant for cardiac function, in a mouse model of dyslipidemia (hApoB+/+;LDLR-/-). 27496881 6 12 theme % 1177:1177 arg1 HRR 1179:1181 a similar 10% HRR 1165:1181 a similar 10% HRR 1165:1181 Despite inducing a similar 10% HRR, ivabradine-treated hearts displayed significantly higher stroke volume values and glycolysis vs. their metoprolol-treated counterparts ex vivo, values for the ivabradine group being often not significantly different from 3-mo-old mice. 27496881 7 13 theme total 1532:1536 arg1 level 1545:1549 the total tissue level 1528:1549 the total tissue level of proteins modified by O-linked N-acetylglucosamine (O-GlcNAc) 1528:1613 Further analyses highlighted additional significant cardiac alterations with disease progression, namely in the total tissue level of proteins modified by O-linked N-acetylglucosamine (O-GlcNAc), whose formation is governed by glucose metabolism via the hexosamine biosynthetic pathway, which showed a similar pattern with ivabradine vs. metoprolol treatment. 27496881 4 14 theme substrate 864:872 arg1 fluxes 874:879 substrate fluxes 864:879 substrate fluxes 864:879 Cardiac function was evaluated in vivo and ex vivo in working hearts perfused with 13C-labeled substrates to assess substrate fluxes through energy metabolic pathways. 27496881 6 15 theme 10 1175:1176 arg1 % 1177:1177 % 1177:1177 % 1177:1177 Despite inducing a similar 10% HRR, ivabradine-treated hearts displayed significantly higher stroke volume values and glycolysis vs. their metoprolol-treated counterparts ex vivo, values for the ivabradine group being often not significantly different from 3-mo-old mice. 27496881 5 16 theme P 1022:1022 arg1 < 1024:1024 P < 0.001 1022:1030 P < 0.001 1022:1030 Compared with 3-mo-old, 6-mo-old dyslipidemic mice had similar cardiac hemodynamics in vivo but impaired (P < 0.001) contractile function (aortic flow: -45%; cardiac output: -34%; stroke volume: -35%) and glycolysis (-24%) ex vivo. 27496881 2 17 theme substrate 500:508 arg1 determinant 531:541 a factor determinant 522:541 a factor determinant for cardiac function 522:562 This study aimed at testing whether similar HRR with ivabradine vs. metoprolol differentially modulates cardiac energy substrate metabolism, a factor determinant for cardiac function, in a mouse model of dyslipidemia (hApoB+/+;LDLR-/-). 27496881 2 17 theme substrate 500:508 arg1 metabolism 510:519 cardiac energy substrate metabolism 485:519 cardiac energy substrate metabolism 485:519 This study aimed at testing whether similar HRR with ivabradine vs. metoprolol differentially modulates cardiac energy substrate metabolism, a factor determinant for cardiac function, in a mouse model of dyslipidemia (hApoB+/+;LDLR-/-). 27496881 0 18 from reduction 102:110 arg1 model 123:127 a mouse model 115:127 a mouse model of dyslipidemia 115:143 Ivabradine and metoprolol differentially affect cardiac glucose metabolism despite similar heart rate reduction in a mouse model of dyslipidemia. 27496881 7 19 link O-linked 1575:1582 arg1 O-GlcNAc 1605:1612 O-GlcNAc 1605:1612 O-GlcNAc 1605:1612 Further analyses highlighted additional significant cardiac alterations with disease progression, namely in the total tissue level of proteins modified by O-linked N-acetylglucosamine (O-GlcNAc), whose formation is governed by glucose metabolism via the hexosamine biosynthetic pathway, which showed a similar pattern with ivabradine vs. metoprolol treatment. 27496881 7 19 link O-linked 1575:1582 arg1 N-acetylglucosamine 1584:1602 O-linked N-acetylglucosamine 1575:1602 O-linked N-acetylglucosamine (O-GlcNAc) 1575:1613 Further analyses highlighted additional significant cardiac alterations with disease progression, namely in the total tissue level of proteins modified by O-linked N-acetylglucosamine (O-GlcNAc), whose formation is governed by glucose metabolism via the hexosamine biosynthetic pathway, which showed a similar pattern with ivabradine vs. metoprolol treatment. 27496881 1 20 theme heart 152:156 arg1 target 184:189 a target 182:189 a target for the management of patients with heart disease 182:239 While heart rate reduction (HRR) is a target for the management of patients with heart disease, contradictory results were reported using ivabradine, which selectively inhibits the pacemaker If current, vs. β-blockers like metoprolol. 27496881 1 20 theme heart 152:156 arg1 HRR 174:176 HRR 174:176 HRR 174:176 While heart rate reduction (HRR) is a target for the management of patients with heart disease, contradictory results were reported using ivabradine, which selectively inhibits the pacemaker If current, vs. β-blockers like metoprolol. 27496881 1 20 theme heart 152:156 arg1 reduction 163:171 heart rate reduction 152:171 heart rate reduction (HRR) 152:177 While heart rate reduction (HRR) is a target for the management of patients with heart disease, contradictory results were reported using ivabradine, which selectively inhibits the pacemaker If current, vs. β-blockers like metoprolol. 27496881 2 21 theme cardiac 485:491 arg1 determinant 531:541 a factor determinant 522:541 a factor determinant for cardiac function 522:562 This study aimed at testing whether similar HRR with ivabradine vs. metoprolol differentially modulates cardiac energy substrate metabolism, a factor determinant for cardiac function, in a mouse model of dyslipidemia (hApoB+/+;LDLR-/-). 27496881 2 21 theme cardiac 485:491 arg1 metabolism 510:519 cardiac energy substrate metabolism 485:519 cardiac energy substrate metabolism 485:519 This study aimed at testing whether similar HRR with ivabradine vs. metoprolol differentially modulates cardiac energy substrate metabolism, a factor determinant for cardiac function, in a mouse model of dyslipidemia (hApoB+/+;LDLR-/-). 27496881 9 22 theme similar 1949:1955 arg1 HRR 1957:1959 similar HRR 1949:1959 similar HRR 1949:1959 Despite similar HRR, ivabradine, but not metoprolol, preserved cardiac function and glucose metabolism during disease progression. 27496881 0 23 theme heart 91:95 arg1 reduction 102:110 similar heart rate reduction 83:110 similar heart rate reduction in a mouse model of dyslipidemia 83:143 Ivabradine and metoprolol differentially affect cardiac glucose metabolism despite similar heart rate reduction in a mouse model of dyslipidemia. 27496881 7 24 theme disease 1497:1503 arg1 progression 1505:1515 disease progression 1497:1515 disease progression 1497:1515 Further analyses highlighted additional significant cardiac alterations with disease progression, namely in the total tissue level of proteins modified by O-linked N-acetylglucosamine (O-GlcNAc), whose formation is governed by glucose metabolism via the hexosamine biosynthetic pathway, which showed a similar pattern with ivabradine vs. metoprolol treatment. 27496881 2 25 theme factor 524:529 arg1 determinant 531:541 a factor determinant 522:541 a factor determinant for cardiac function 522:562 This study aimed at testing whether similar HRR with ivabradine vs. metoprolol differentially modulates cardiac energy substrate metabolism, a factor determinant for cardiac function, in a mouse model of dyslipidemia (hApoB+/+;LDLR-/-). 27496881 2 25 theme factor 524:529 arg1 metabolism 510:519 cardiac energy substrate metabolism 485:519 cardiac energy substrate metabolism 485:519 This study aimed at testing whether similar HRR with ivabradine vs. metoprolol differentially modulates cardiac energy substrate metabolism, a factor determinant for cardiac function, in a mouse model of dyslipidemia (hApoB+/+;LDLR-/-). 27496881 6 26 theme volume 1248:1253 arg1 values 1255:1260 stroke volume values 1241:1260 stroke volume values 1241:1260 Despite inducing a similar 10% HRR, ivabradine-treated hearts displayed significantly higher stroke volume values and glycolysis vs. their metoprolol-treated counterparts ex vivo, values for the ivabradine group being often not significantly different from 3-mo-old mice. 27496881 6 27 theme higher 1234:1239 arg1 values 1255:1260 stroke volume values 1241:1260 stroke volume values 1241:1260 Despite inducing a similar 10% HRR, ivabradine-treated hearts displayed significantly higher stroke volume values and glycolysis vs. their metoprolol-treated counterparts ex vivo, values for the ivabradine group being often not significantly different from 3-mo-old mice. 27496881 5 28 theme flow 1062:1065 arg1 % 1071:1071 aortic flow: -45% 1055:1071 aortic flow: -45%; cardiac output: -34%; stroke volume: -35% 1055:1114 Compared with 3-mo-old, 6-mo-old dyslipidemic mice had similar cardiac hemodynamics in vivo but impaired (P < 0.001) contractile function (aortic flow: -45%; cardiac output: -34%; stroke volume: -35%) and glycolysis (-24%) ex vivo. 27496881 5 29 theme dyslipidemic 949:960 arg1 mice 962:965 6-mo-old dyslipidemic mice 940:965 6-mo-old dyslipidemic mice 940:965 Compared with 3-mo-old, 6-mo-old dyslipidemic mice had similar cardiac hemodynamics in vivo but impaired (P < 0.001) contractile function (aortic flow: -45%; cardiac output: -34%; stroke volume: -35%) and glycolysis (-24%) ex vivo. 27496881 9 30 theme cardiac 2004:2010 arg1 function 2012:2019 cardiac function 2004:2019 cardiac function 2004:2019 Despite similar HRR, ivabradine, but not metoprolol, preserved cardiac function and glucose metabolism during disease progression. 27496881 2 31 theme similar 417:423 arg1 HRR 425:427 similar HRR 417:427 similar HRR with ivabradine vs. metoprolol 417:458 This study aimed at testing whether similar HRR with ivabradine vs. metoprolol differentially modulates cardiac energy substrate metabolism, a factor determinant for cardiac function, in a mouse model of dyslipidemia (hApoB+/+;LDLR-/-). 27496881 3 32 used used 660:663 arg2 we 657:658 we 657:658 we 657:658 Following a longitudinal study design, we used 3- and 6-mo-old mice, untreated or treated for 3 mo with ivabradine or metoprolol. 27496881 7 33 from alterations 1480:1490 arg1 level 1545:1549 the total tissue level 1528:1549 the total tissue level of proteins modified by O-linked N-acetylglucosamine (O-GlcNAc) 1528:1613 Further analyses highlighted additional significant cardiac alterations with disease progression, namely in the total tissue level of proteins modified by O-linked N-acetylglucosamine (O-GlcNAc), whose formation is governed by glucose metabolism via the hexosamine biosynthetic pathway, which showed a similar pattern with ivabradine vs. metoprolol treatment. 27496881 7 34 theme additional 1449:1458 arg1 alterations 1480:1490 additional significant cardiac alterations 1449:1490 additional significant cardiac alterations 1449:1490 Further analyses highlighted additional significant cardiac alterations with disease progression, namely in the total tissue level of proteins modified by O-linked N-acetylglucosamine (O-GlcNAc), whose formation is governed by glucose metabolism via the hexosamine biosynthetic pathway, which showed a similar pattern with ivabradine vs. metoprolol treatment. 27496881 7 35 theme O-linked 1575:1582 arg1 O-GlcNAc 1605:1612 O-GlcNAc 1605:1612 O-GlcNAc 1605:1612 Further analyses highlighted additional significant cardiac alterations with disease progression, namely in the total tissue level of proteins modified by O-linked N-acetylglucosamine (O-GlcNAc), whose formation is governed by glucose metabolism via the hexosamine biosynthetic pathway, which showed a similar pattern with ivabradine vs. metoprolol treatment. 27496881 7 35 theme O-linked 1575:1582 arg1 N-acetylglucosamine 1584:1602 O-linked N-acetylglucosamine 1575:1602 O-linked N-acetylglucosamine (O-GlcNAc) 1575:1613 Further analyses highlighted additional significant cardiac alterations with disease progression, namely in the total tissue level of proteins modified by O-linked N-acetylglucosamine (O-GlcNAc), whose formation is governed by glucose metabolism via the hexosamine biosynthetic pathway, which showed a similar pattern with ivabradine vs. metoprolol treatment. 27496881 5 36 dep % 1071:1071 arg1 output 1082:1087 cardiac output 1074:1087 aortic flow: -45%; cardiac output: -34%; stroke volume: -35% 1055:1114 Compared with 3-mo-old, 6-mo-old dyslipidemic mice had similar cardiac hemodynamics in vivo but impaired (P < 0.001) contractile function (aortic flow: -45%; cardiac output: -34%; stroke volume: -35%) and glycolysis (-24%) ex vivo. 27496881 5 36 dep % 1071:1071 arg1 % 1093:1093 -34% 1090:1093 aortic flow: -45%; cardiac output: -34%; stroke volume: -35% 1055:1114 Compared with 3-mo-old, 6-mo-old dyslipidemic mice had similar cardiac hemodynamics in vivo but impaired (P < 0.001) contractile function (aortic flow: -45%; cardiac output: -34%; stroke volume: -35%) and glycolysis (-24%) ex vivo. 27496881 5 36 dep % 1071:1071 arg1 volume 1103:1108 stroke volume 1096:1108 aortic flow: -45%; cardiac output: -34%; stroke volume: -35% 1055:1114 Compared with 3-mo-old, 6-mo-old dyslipidemic mice had similar cardiac hemodynamics in vivo but impaired (P < 0.001) contractile function (aortic flow: -45%; cardiac output: -34%; stroke volume: -35%) and glycolysis (-24%) ex vivo. 27496881 5 36 dep % 1071:1071 arg1 % 1114:1114 -35% 1111:1114 aortic flow: -45%; cardiac output: -34%; stroke volume: -35% 1055:1114 Compared with 3-mo-old, 6-mo-old dyslipidemic mice had similar cardiac hemodynamics in vivo but impaired (P < 0.001) contractile function (aortic flow: -45%; cardiac output: -34%; stroke volume: -35%) and glycolysis (-24%) ex vivo. 27496881 3 37 theme longitudinal 630:641 arg1 design 649:654 a longitudinal study design 628:654 a longitudinal study design 628:654 Following a longitudinal study design, we used 3- and 6-mo-old mice, untreated or treated for 3 mo with ivabradine or metoprolol. 27496881 8 38 from alterations 1835:1845 arg1 metabolism 1866:1875 cardiac glucose metabolism 1850:1875 cardiac glucose metabolism 1850:1875 Collectively, our results emphasize the implication of alterations in cardiac glucose metabolism and signaling linked to disease progression in our mouse model. 27496881 8 38 from alterations 1835:1845 arg1 signaling 1881:1889 signaling 1881:1889 signaling 1881:1889 Collectively, our results emphasize the implication of alterations in cardiac glucose metabolism and signaling linked to disease progression in our mouse model. 27496881 0 39 theme glucose 56:62 arg1 metabolism 64:73 cardiac glucose metabolism 48:73 cardiac glucose metabolism 48:73 Ivabradine and metoprolol differentially affect cardiac glucose metabolism despite similar heart rate reduction in a mouse model of dyslipidemia. 27496881 8 40 from implication 1820:1830 arg1 metabolism 1866:1875 cardiac glucose metabolism 1850:1875 cardiac glucose metabolism 1850:1875 Collectively, our results emphasize the implication of alterations in cardiac glucose metabolism and signaling linked to disease progression in our mouse model. 27496881 8 40 from implication 1820:1830 arg1 signaling 1881:1889 signaling 1881:1889 signaling 1881:1889 Collectively, our results emphasize the implication of alterations in cardiac glucose metabolism and signaling linked to disease progression in our mouse model. 27496881 8 40 from implication 1820:1830 arg1 model 1934:1938 our mouse model 1924:1938 our mouse model 1924:1938 Collectively, our results emphasize the implication of alterations in cardiac glucose metabolism and signaling linked to disease progression in our mouse model. 27496881 4 41 theme Cardiac 748:754 arg1 function 756:763 Cardiac function 748:763 Cardiac function 748:763 Cardiac function was evaluated in vivo and ex vivo in working hearts perfused with 13C-labeled substrates to assess substrate fluxes through energy metabolic pathways. 27496881 6 42 dep significantly 1376:1388 arg1 not 1372:1374 not 1372:1374 not 1372:1374 Despite inducing a similar 10% HRR, ivabradine-treated hearts displayed significantly higher stroke volume values and glycolysis vs. their metoprolol-treated counterparts ex vivo, values for the ivabradine group being often not significantly different from 3-mo-old mice. 27496881 8 43 from metabolism 1866:1875 arg1 implication 1820:1830 the implication 1816:1830 the implication of alterations in cardiac glucose metabolism and signaling linked to disease progression in our mouse model 1816:1938 Collectively, our results emphasize the implication of alterations in cardiac glucose metabolism and signaling linked to disease progression in our mouse model. 27496881 9 44 theme disease 2051:2057 arg1 progression 2059:2069 disease progression 2051:2069 disease progression 2051:2069 Despite similar HRR, ivabradine, but not metoprolol, preserved cardiac function and glucose metabolism during disease progression. 27496881 1 45 theme patients 213:220 arg1 management 199:208 the management 195:208 the management of patients with heart disease 195:239 While heart rate reduction (HRR) is a target for the management of patients with heart disease, contradictory results were reported using ivabradine, which selectively inhibits the pacemaker If current, vs. β-blockers like metoprolol. 27496881 5 46 theme cardiac 979:985 arg1 hemodynamics 987:998 similar cardiac hemodynamics 971:998 similar cardiac hemodynamics 971:998 Compared with 3-mo-old, 6-mo-old dyslipidemic mice had similar cardiac hemodynamics in vivo but impaired (P < 0.001) contractile function (aortic flow: -45%; cardiac output: -34%; stroke volume: -35%) and glycolysis (-24%) ex vivo. 27496881 8 47 theme mouse 1928:1932 arg1 model 1934:1938 our mouse model 1924:1938 our mouse model 1924:1938 Collectively, our results emphasize the implication of alterations in cardiac glucose metabolism and signaling linked to disease progression in our mouse model. 27496881 6 48 theme similar 1167:1173 arg1 HRR 1179:1181 a similar 10% HRR 1165:1181 a similar 10% HRR 1165:1181 Despite inducing a similar 10% HRR, ivabradine-treated hearts displayed significantly higher stroke volume values and glycolysis vs. their metoprolol-treated counterparts ex vivo, values for the ivabradine group being often not significantly different from 3-mo-old mice. 27496881 1 49 theme heart 227:231 arg1 disease 233:239 heart disease 227:239 heart disease 227:239 While heart rate reduction (HRR) is a target for the management of patients with heart disease, contradictory results were reported using ivabradine, which selectively inhibits the pacemaker If current, vs. β-blockers like metoprolol. 27496881 2 50 theme dyslipidemia 585:596 arg1 model 576:580 a mouse model 568:580 a mouse model of dyslipidemia (hApoB+/+;LDLR-/-) 568:615 This study aimed at testing whether similar HRR with ivabradine vs. metoprolol differentially modulates cardiac energy substrate metabolism, a factor determinant for cardiac function, in a mouse model of dyslipidemia (hApoB+/+;LDLR-/-). 27496881 7 51 theme similar 1722:1728 arg1 pattern 1730:1736 a similar pattern 1720:1736 a similar pattern 1720:1736 Further analyses highlighted additional significant cardiac alterations with disease progression, namely in the total tissue level of proteins modified by O-linked N-acetylglucosamine (O-GlcNAc), whose formation is governed by glucose metabolism via the hexosamine biosynthetic pathway, which showed a similar pattern with ivabradine vs. metoprolol treatment. 27496881 5 52 contain had 967:969 arg1 mice 962:965 6-mo-old dyslipidemic mice 940:965 6-mo-old dyslipidemic mice 940:965 Compared with 3-mo-old, 6-mo-old dyslipidemic mice had similar cardiac hemodynamics in vivo but impaired (P < 0.001) contractile function (aortic flow: -45%; cardiac output: -34%; stroke volume: -35%) and glycolysis (-24%) ex vivo. 27496881 5 52 contain had 967:969 arg2 hemodynamics 987:998 similar cardiac hemodynamics 971:998 similar cardiac hemodynamics 971:998 Compared with 3-mo-old, 6-mo-old dyslipidemic mice had similar cardiac hemodynamics in vivo but impaired (P < 0.001) contractile function (aortic flow: -45%; cardiac output: -34%; stroke volume: -35%) and glycolysis (-24%) ex vivo. 27496881 6 53 theme ivabradine 1343:1352 arg1 group 1354:1358 the ivabradine group 1339:1358 the ivabradine group 1339:1358 Despite inducing a similar 10% HRR, ivabradine-treated hearts displayed significantly higher stroke volume values and glycolysis vs. their metoprolol-treated counterparts ex vivo, values for the ivabradine group being often not significantly different from 3-mo-old mice. 27496881 8 54 from signaling 1881:1889 arg1 implication 1820:1830 the implication 1816:1830 the implication of alterations in cardiac glucose metabolism and signaling linked to disease progression in our mouse model 1816:1938 Collectively, our results emphasize the implication of alterations in cardiac glucose metabolism and signaling linked to disease progression in our mouse model. 27496881 6 55 theme metoprolol-treated 1287:1304 arg1 counterparts 1306:1317 their metoprolol-treated counterparts 1281:1317 their metoprolol-treated counterparts 1281:1317 Despite inducing a similar 10% HRR, ivabradine-treated hearts displayed significantly higher stroke volume values and glycolysis vs. their metoprolol-treated counterparts ex vivo, values for the ivabradine group being often not significantly different from 3-mo-old mice. 27496881 2 56 dep hApoB+/+ 599:606 arg1 LDLR-/- 608:614 LDLR-/- 608:614 LDLR-/- 608:614 This study aimed at testing whether similar HRR with ivabradine vs. metoprolol differentially modulates cardiac energy substrate metabolism, a factor determinant for cardiac function, in a mouse model of dyslipidemia (hApoB+/+;LDLR-/-). 27496881 7 57 theme biosynthetic 1685:1696 arg1 pathway 1698:1704 the hexosamine biosynthetic pathway 1670:1704 the hexosamine biosynthetic pathway 1670:1704 Further analyses highlighted additional significant cardiac alterations with disease progression, namely in the total tissue level of proteins modified by O-linked N-acetylglucosamine (O-GlcNAc), whose formation is governed by glucose metabolism via the hexosamine biosynthetic pathway, which showed a similar pattern with ivabradine vs. metoprolol treatment. 27496881 8 58 theme glucose 1858:1864 arg1 metabolism 1866:1875 cardiac glucose metabolism 1850:1875 cardiac glucose metabolism 1850:1875 Collectively, our results emphasize the implication of alterations in cardiac glucose metabolism and signaling linked to disease progression in our mouse model. 27496881 2 59 theme cardiac 547:553 arg1 function 555:562 cardiac function 547:562 cardiac function 547:562 This study aimed at testing whether similar HRR with ivabradine vs. metoprolol differentially modulates cardiac energy substrate metabolism, a factor determinant for cardiac function, in a mouse model of dyslipidemia (hApoB+/+;LDLR-/-). 27496881 6 60 theme 3-mo-old 1405:1412 arg1 mice 1414:1417 3-mo-old mice 1405:1417 3-mo-old mice 1405:1417 Despite inducing a similar 10% HRR, ivabradine-treated hearts displayed significantly higher stroke volume values and glycolysis vs. their metoprolol-treated counterparts ex vivo, values for the ivabradine group being often not significantly different from 3-mo-old mice. 27496881 7 61 theme tissue 1538:1543 arg1 level 1545:1549 the total tissue level 1528:1549 the total tissue level of proteins modified by O-linked N-acetylglucosamine (O-GlcNAc) 1528:1613 Further analyses highlighted additional significant cardiac alterations with disease progression, namely in the total tissue level of proteins modified by O-linked N-acetylglucosamine (O-GlcNAc), whose formation is governed by glucose metabolism via the hexosamine biosynthetic pathway, which showed a similar pattern with ivabradine vs. metoprolol treatment. 27496881 4 62 theme energy 889:894 arg1 pathways 906:913 energy metabolic pathways 889:913 energy metabolic pathways 889:913 Cardiac function was evaluated in vivo and ex vivo in working hearts perfused with 13C-labeled substrates to assess substrate fluxes through energy metabolic pathways. 27496881 7 63 with alterations 1480:1490 arg1 progression 1505:1515 disease progression 1497:1515 disease progression 1497:1515 Further analyses highlighted additional significant cardiac alterations with disease progression, namely in the total tissue level of proteins modified by O-linked N-acetylglucosamine (O-GlcNAc), whose formation is governed by glucose metabolism via the hexosamine biosynthetic pathway, which showed a similar pattern with ivabradine vs. metoprolol treatment. 27496881 2 64 dep dyslipidemia 585:596 arg1 hApoB+/+ 599:606 hApoB+/+ 599:606 hApoB+/+ 599:606 This study aimed at testing whether similar HRR with ivabradine vs. metoprolol differentially modulates cardiac energy substrate metabolism, a factor determinant for cardiac function, in a mouse model of dyslipidemia (hApoB+/+;LDLR-/-). 27496881 8 65 theme disease 1901:1907 arg1 progression 1909:1919 disease progression 1901:1919 disease progression 1901:1919 Collectively, our results emphasize the implication of alterations in cardiac glucose metabolism and signaling linked to disease progression in our mouse model. 27496881 2 66 with HRR 425:427 arg1 metoprolol 449:458 metoprolol 449:458 metoprolol 449:458 This study aimed at testing whether similar HRR with ivabradine vs. metoprolol differentially modulates cardiac energy substrate metabolism, a factor determinant for cardiac function, in a mouse model of dyslipidemia (hApoB+/+;LDLR-/-). 27496881 2 66 with HRR 425:427 arg1 ivabradine 434:443 ivabradine 434:443 ivabradine 434:443 This study aimed at testing whether similar HRR with ivabradine vs. metoprolol differentially modulates cardiac energy substrate metabolism, a factor determinant for cardiac function, in a mouse model of dyslipidemia (hApoB+/+;LDLR-/-). 27496881 7 67 theme hexosamine 1674:1683 arg1 pathway 1698:1704 the hexosamine biosynthetic pathway 1670:1704 the hexosamine biosynthetic pathway 1670:1704 Further analyses highlighted additional significant cardiac alterations with disease progression, namely in the total tissue level of proteins modified by O-linked N-acetylglucosamine (O-GlcNAc), whose formation is governed by glucose metabolism via the hexosamine biosynthetic pathway, which showed a similar pattern with ivabradine vs. metoprolol treatment. 27496881 0 68 theme similar 83:89 arg1 reduction 102:110 similar heart rate reduction 83:110 similar heart rate reduction in a mouse model of dyslipidemia 83:143 Ivabradine and metoprolol differentially affect cardiac glucose metabolism despite similar heart rate reduction in a mouse model of dyslipidemia. 27496881 2 69 theme energy 493:498 arg1 determinant 531:541 a factor determinant 522:541 a factor determinant for cardiac function 522:562 This study aimed at testing whether similar HRR with ivabradine vs. metoprolol differentially modulates cardiac energy substrate metabolism, a factor determinant for cardiac function, in a mouse model of dyslipidemia (hApoB+/+;LDLR-/-). 27496881 2 69 theme energy 493:498 arg1 metabolism 510:519 cardiac energy substrate metabolism 485:519 cardiac energy substrate metabolism 485:519 This study aimed at testing whether similar HRR with ivabradine vs. metoprolol differentially modulates cardiac energy substrate metabolism, a factor determinant for cardiac function, in a mouse model of dyslipidemia (hApoB+/+;LDLR-/-). 27496881 8 70 attach linked 1891:1896 arg1 progression 1909:1919 disease progression 1901:1919 disease progression 1901:1919 Collectively, our results emphasize the implication of alterations in cardiac glucose metabolism and signaling linked to disease progression in our mouse model. 27496881 8 70 attach linked 1891:1896 arg2 alterations 1835:1845 alterations 1835:1845 alterations in cardiac glucose metabolism and signaling linked to disease progression 1835:1919 Collectively, our results emphasize the implication of alterations in cardiac glucose metabolism and signaling linked to disease progression in our mouse model. 27496881 0 71 theme rate 97:100 arg1 reduction 102:110 similar heart rate reduction 83:110 similar heart rate reduction in a mouse model of dyslipidemia 83:143 Ivabradine and metoprolol differentially affect cardiac glucose metabolism despite similar heart rate reduction in a mouse model of dyslipidemia. 27496881 1 72 theme rate 158:161 arg1 target 184:189 a target 182:189 a target for the management of patients with heart disease 182:239 While heart rate reduction (HRR) is a target for the management of patients with heart disease, contradictory results were reported using ivabradine, which selectively inhibits the pacemaker If current, vs. β-blockers like metoprolol. 27496881 1 72 theme rate 158:161 arg1 HRR 174:176 HRR 174:176 HRR 174:176 While heart rate reduction (HRR) is a target for the management of patients with heart disease, contradictory results were reported using ivabradine, which selectively inhibits the pacemaker If current, vs. β-blockers like metoprolol. 27496881 1 72 theme rate 158:161 arg1 reduction 163:171 heart rate reduction 152:171 heart rate reduction (HRR) 152:177 While heart rate reduction (HRR) is a target for the management of patients with heart disease, contradictory results were reported using ivabradine, which selectively inhibits the pacemaker If current, vs. β-blockers like metoprolol. 27496881 7 73 theme glucose 1647:1653 arg1 metabolism 1655:1664 glucose metabolism 1647:1664 glucose metabolism 1647:1664 Further analyses highlighted additional significant cardiac alterations with disease progression, namely in the total tissue level of proteins modified by O-linked N-acetylglucosamine (O-GlcNAc), whose formation is governed by glucose metabolism via the hexosamine biosynthetic pathway, which showed a similar pattern with ivabradine vs. metoprolol treatment. 27496881 5 74 theme cardiac 1074:1080 arg1 output 1082:1087 cardiac output 1074:1087 aortic flow: -45%; cardiac output: -34%; stroke volume: -35% 1055:1114 Compared with 3-mo-old, 6-mo-old dyslipidemic mice had similar cardiac hemodynamics in vivo but impaired (P < 0.001) contractile function (aortic flow: -45%; cardiac output: -34%; stroke volume: -35%) and glycolysis (-24%) ex vivo. 27496881 7 75 theme cardiac 1472:1478 arg1 alterations 1480:1490 additional significant cardiac alterations 1449:1490 additional significant cardiac alterations 1449:1490 Further analyses highlighted additional significant cardiac alterations with disease progression, namely in the total tissue level of proteins modified by O-linked N-acetylglucosamine (O-GlcNAc), whose formation is governed by glucose metabolism via the hexosamine biosynthetic pathway, which showed a similar pattern with ivabradine vs. metoprolol treatment. 27496881 1 76 with patients 213:220 arg1 disease 233:239 heart disease 227:239 heart disease 227:239 While heart rate reduction (HRR) is a target for the management of patients with heart disease, contradictory results were reported using ivabradine, which selectively inhibits the pacemaker If current, vs. β-blockers like metoprolol. 27496881 0 77 theme mouse 117:121 arg1 model 123:127 a mouse model 115:127 a mouse model of dyslipidemia 115:143 Ivabradine and metoprolol differentially affect cardiac glucose metabolism despite similar heart rate reduction in a mouse model of dyslipidemia. 27496881 5 78 theme aortic 1055:1060 arg1 % 1071:1071 aortic flow: -45% 1055:1071 aortic flow: -45%; cardiac output: -34%; stroke volume: -35% 1055:1114 Compared with 3-mo-old, 6-mo-old dyslipidemic mice had similar cardiac hemodynamics in vivo but impaired (P < 0.001) contractile function (aortic flow: -45%; cardiac output: -34%; stroke volume: -35%) and glycolysis (-24%) ex vivo. 27496881 5 79 theme 6-mo-old 940:947 arg1 mice 962:965 6-mo-old dyslipidemic mice 940:965 6-mo-old dyslipidemic mice 940:965 Compared with 3-mo-old, 6-mo-old dyslipidemic mice had similar cardiac hemodynamics in vivo but impaired (P < 0.001) contractile function (aortic flow: -45%; cardiac output: -34%; stroke volume: -35%) and glycolysis (-24%) ex vivo. 27496881 5 80 dep function 1045:1052 arg1 % 1071:1071 aortic flow: -45% 1055:1071 aortic flow: -45%; cardiac output: -34%; stroke volume: -35% 1055:1114 Compared with 3-mo-old, 6-mo-old dyslipidemic mice had similar cardiac hemodynamics in vivo but impaired (P < 0.001) contractile function (aortic flow: -45%; cardiac output: -34%; stroke volume: -35%) and glycolysis (-24%) ex vivo. 27496881 6 81 theme stroke 1241:1246 arg1 values 1255:1260 stroke volume values 1241:1260 stroke volume values 1241:1260 Despite inducing a similar 10% HRR, ivabradine-treated hearts displayed significantly higher stroke volume values and glycolysis vs. their metoprolol-treated counterparts ex vivo, values for the ivabradine group being often not significantly different from 3-mo-old mice. 27496881 6 82 from mice 1414:1417 arg1 different 1390:1398 different 1390:1398 different 1390:1398 Despite inducing a similar 10% HRR, ivabradine-treated hearts displayed significantly higher stroke volume values and glycolysis vs. their metoprolol-treated counterparts ex vivo, values for the ivabradine group being often not significantly different from 3-mo-old mice. 27496881 5 83 theme stroke 1096:1101 arg1 volume 1103:1108 stroke volume 1096:1108 aortic flow: -45%; cardiac output: -34%; stroke volume: -35% 1055:1114 Compared with 3-mo-old, 6-mo-old dyslipidemic mice had similar cardiac hemodynamics in vivo but impaired (P < 0.001) contractile function (aortic flow: -45%; cardiac output: -34%; stroke volume: -35%) and glycolysis (-24%) ex vivo. 27496881 0 84 theme cardiac 48:54 arg1 metabolism 64:73 cardiac glucose metabolism 48:73 cardiac glucose metabolism 48:73 Ivabradine and metoprolol differentially affect cardiac glucose metabolism despite similar heart rate reduction in a mouse model of dyslipidemia. 27496881 7 85 theme significant 1460:1470 arg1 alterations 1480:1490 additional significant cardiac alterations 1449:1490 additional significant cardiac alterations 1449:1490 Further analyses highlighted additional significant cardiac alterations with disease progression, namely in the total tissue level of proteins modified by O-linked N-acetylglucosamine (O-GlcNAc), whose formation is governed by glucose metabolism via the hexosamine biosynthetic pathway, which showed a similar pattern with ivabradine vs. metoprolol treatment. 27496881 6 86 theme ivabradine-treated 1184:1201 arg1 hearts 1203:1208 ivabradine-treated hearts 1184:1208 ivabradine-treated hearts 1184:1208 Despite inducing a similar 10% HRR, ivabradine-treated hearts displayed significantly higher stroke volume values and glycolysis vs. their metoprolol-treated counterparts ex vivo, values for the ivabradine group being often not significantly different from 3-mo-old mice. 27496881 9 87 theme glucose 2025:2031 arg1 metabolism 2033:2042 glucose metabolism 2025:2042 glucose metabolism 2025:2042 Despite similar HRR, ivabradine, but not metoprolol, preserved cardiac function and glucose metabolism during disease progression. 27496881 7 88 theme Further 1420:1426 arg1 analyses 1428:1435 Further analyses 1420:1435 Further analyses 1420:1435 Further analyses highlighted additional significant cardiac alterations with disease progression, namely in the total tissue level of proteins modified by O-linked N-acetylglucosamine (O-GlcNAc), whose formation is governed by glucose metabolism via the hexosamine biosynthetic pathway, which showed a similar pattern with ivabradine vs. metoprolol treatment. 27496881 3 89 theme study 643:647 arg1 design 649:654 a longitudinal study design 628:654 a longitudinal study design 628:654 Following a longitudinal study design, we used 3- and 6-mo-old mice, untreated or treated for 3 mo with ivabradine or metoprolol. 27496881 5 90 theme similar 971:977 arg1 hemodynamics 987:998 similar cardiac hemodynamics 971:998 similar cardiac hemodynamics 971:998 Compared with 3-mo-old, 6-mo-old dyslipidemic mice had similar cardiac hemodynamics in vivo but impaired (P < 0.001) contractile function (aortic flow: -45%; cardiac output: -34%; stroke volume: -35%) and glycolysis (-24%) ex vivo. 27496881 7 91 theme metoprolol 1758:1767 arg1 treatment 1769:1777 metoprolol treatment 1758:1777 metoprolol treatment 1758:1777 Further analyses highlighted additional significant cardiac alterations with disease progression, namely in the total tissue level of proteins modified by O-linked N-acetylglucosamine (O-GlcNAc), whose formation is governed by glucose metabolism via the hexosamine biosynthetic pathway, which showed a similar pattern with ivabradine vs. metoprolol treatment. 27297885 1 0 theme target 235:240 arg1 proteins 242:249 49 potential target proteins 222:249 49 potential target proteins 222:249 Protein O-fucosyltransferase 2 (POFUT2) adds O-linked fucose to Thrombospondin Type 1 Repeats (TSR) in 49 potential target proteins. 27297885 9 1 theme Conditional 1646:1656 arg1 deletion 1658:1665 Conditional deletion 1646:1665 Conditional deletion of either Pofut2 or Adamts9 in the epiblast 1646:1709 Conditional deletion of either Pofut2 or Adamts9 in the epiblast rescues the gastrulation defects, and identified a new role for O-fucosylated ADAMTS9 during morphogenesis of the amnion and axial mesendoderm. 27297885 8 2 theme primitive 1628:1636 arg1 cells 1492:1496 trophoblast giant cells 1474:1496 trophoblast giant cells 1474:1496 We determined that Adamts9 was dynamically expressed during mouse gastrulation by trophoblast giant cells, parietal endoderm, the most proximal visceral endoderm adjacent to the ectoplacental cone, extraembryonic mesoderm, and anterior primitive streak. 27297885 8 2 theme primitive 1628:1636 arg1 streak 1638:1643 anterior primitive streak 1619:1643 anterior primitive streak 1619:1643 We determined that Adamts9 was dynamically expressed during mouse gastrulation by trophoblast giant cells, parietal endoderm, the most proximal visceral endoderm adjacent to the ectoplacental cone, extraembryonic mesoderm, and anterior primitive streak. 27297885 2 3 dep Disintegrin 299:309 arg1 A 297:297 A 297:297 A 297:297 Nearly half the POFUT2 targets belong to the A Disintegrin and Metalloprotease with ThromboSpondin type-1 motifs (ADAMTS) or ADAMTS-like family of proteins. 27297885 10 4 theme embryonic 1932:1940 arg1 tissue 1942:1947 the extra embryonic tissue 1922:1947 the extra embryonic tissue 1922:1947 Combined, these results suggested that loss of ADAMTS9 function in the extra embryonic tissue is responsible for gastrulation defects in the Pofut2 knockout. 27297885 3 5 theme embryonic 513:521 arg1 lethality 523:531 early embryonic lethality 507:531 early embryonic lethality 507:531 Both the mouse Pofut2 RST434 gene trap allele and the Adamts9 knockout were reported to result in early embryonic lethality, suggesting that defects in Pofut2 mutant embryos could result from loss of O-fucosylation on ADAMTS9. 27297885 12 6 from ectoderm 2252:2259 arg1 input 2222:2226 input 2222:2226 input from the extraembryonic ectoderm and/or compression of the epiblast 2222:2294 Consequently, loss of input from the extraembryonic ectoderm and/or compression of the epiblast by Reichert's membrane blocks gastrulation. 27297885 12 6 from ectoderm 2252:2259 arg1 loss 2214:2217 loss 2214:2217 loss of input from the extraembryonic ectoderm and/or compression of the epiblast by Reichert's membrane 2214:2317 Consequently, loss of input from the extraembryonic ectoderm and/or compression of the epiblast by Reichert's membrane blocks gastrulation. 27297885 4 7 theme O-fucosylated 809:821 arg1 ADAMTS9 823:829 O-fucosylated ADAMTS9 809:829 O-fucosylated ADAMTS9 809:829 To address this question, we compared the Pofut2 and Adamts9 knockout phenotypes and used Cre-mediated deletion of Pofut2 and Adamts9 to dissect the tissue-specific role of O-fucosylated ADAMTS9 during gastrulation. 27297885 13 8 theme tissues 2523:2529 arg1 organization 2507:2518 the organization 2503:2518 the organization of tissues 2503:2529 In the future, the Pofut2 and Adamts9 knockouts will be valuable tools for understanding how local changes in the properties of the extracellular matrix influence the organization of tissues during mammalian development. 27297885 9 9 theme Pofut2 1677:1682 arg1 deletion 1658:1665 Conditional deletion 1646:1665 Conditional deletion of either Pofut2 or Adamts9 in the epiblast 1646:1709 Conditional deletion of either Pofut2 or Adamts9 in the epiblast rescues the gastrulation defects, and identified a new role for O-fucosylated ADAMTS9 during morphogenesis of the amnion and axial mesendoderm. 27297885 13 10 theme mammalian 2538:2546 arg1 development 2548:2558 mammalian development 2538:2558 mammalian development 2538:2558 In the future, the Pofut2 and Adamts9 knockouts will be valuable tools for understanding how local changes in the properties of the extracellular matrix influence the organization of tissues during mammalian development. 27297885 1 11 theme Thrombospondin 183:196 arg1 Type 198:201 Thrombospondin Type 1 183:203 Thrombospondin Type 1 Repeats (TSR) in 49 potential target proteins 183:249 Protein O-fucosyltransferase 2 (POFUT2) adds O-linked fucose to Thrombospondin Type 1 Repeats (TSR) in 49 potential target proteins. 27297885 9 12 theme Adamts9 1687:1693 arg1 deletion 1658:1665 Conditional deletion 1646:1665 Conditional deletion of either Pofut2 or Adamts9 in the epiblast 1646:1709 Conditional deletion of either Pofut2 or Adamts9 in the epiblast rescues the gastrulation defects, and identified a new role for O-fucosylated ADAMTS9 during morphogenesis of the amnion and axial mesendoderm. 27297885 12 13 from loss 2214:2217 arg1 compression 2268:2278 compression 2268:2278 compression 2268:2278 Consequently, loss of input from the extraembryonic ectoderm and/or compression of the epiblast by Reichert's membrane blocks gastrulation. 27297885 12 13 from loss 2214:2217 arg1 ectoderm 2252:2259 extraembryonic ectoderm 2237:2259 extraembryonic ectoderm 2237:2259 Consequently, loss of input from the extraembryonic ectoderm and/or compression of the epiblast by Reichert's membrane blocks gastrulation. 27297885 4 14 gly O-fucosylated 809:821 arg1 ADAMTS9 823:829 O-fucosylated ADAMTS9 809:829 O-fucosylated ADAMTS9 809:829 To address this question, we compared the Pofut2 and Adamts9 knockout phenotypes and used Cre-mediated deletion of Pofut2 and Adamts9 to dissect the tissue-specific role of O-fucosylated ADAMTS9 during gastrulation. 27297885 11 15 theme ADAMTS9 2041:2047 arg1 function 2049:2056 ADAMTS9 function 2041:2056 ADAMTS9 function 2041:2056 We hypothesize that loss of ADAMTS9 function in the most proximal visceral endoderm leads to slippage of the visceral endoderm and altered characteristics of the extraembryonic ectoderm. 27297885 6 16 theme function 1194:1201 arg1 disruption 1172:1181 disruption 1172:1181 disruption of ADAMTS9 function 1172:1201 The similarity between Pofut2 and Adamts9 mutants suggested that disruption of ADAMTS9 function could be responsible for the gastrulation defects observed in Pofut2 mutants. 27297885 3 17 theme mutant 568:573 arg1 embryos 575:581 Pofut2 mutant embryos 561:581 Pofut2 mutant embryos 561:581 Both the mouse Pofut2 RST434 gene trap allele and the Adamts9 knockout were reported to result in early embryonic lethality, suggesting that defects in Pofut2 mutant embryos could result from loss of O-fucosylation on ADAMTS9. 27297885 1 18 from Repeats 205:211 arg1 proteins 242:249 49 potential target proteins 222:249 49 potential target proteins 222:249 Protein O-fucosyltransferase 2 (POFUT2) adds O-linked fucose to Thrombospondin Type 1 Repeats (TSR) in 49 potential target proteins. 27297885 9 19 from deletion 1658:1665 arg1 epiblast 1702:1709 the epiblast 1698:1709 the epiblast 1698:1709 Conditional deletion of either Pofut2 or Adamts9 in the epiblast rescues the gastrulation defects, and identified a new role for O-fucosylated ADAMTS9 during morphogenesis of the amnion and axial mesendoderm. 27297885 11 20 theme visceral 2079:2086 arg1 endoderm 2088:2095 the most proximal visceral endoderm 2061:2095 the most proximal visceral endoderm 2061:2095 We hypothesize that loss of ADAMTS9 function in the most proximal visceral endoderm leads to slippage of the visceral endoderm and altered characteristics of the extraembryonic ectoderm. 27297885 7 21 theme POFUT2 1338:1343 arg1 knockout 1326:1333 knockout 1326:1333 knockout 1326:1333 Consistent with this prediction, CRISPR/Cas9 knockout of POFUT2 in HEK293T cells blocked secretion of ADAMTS9. 27297885 5 22 theme disorganized 973:984 arg1 epithelia 986:994 disorganized epithelia 973:994 disorganized epithelia (epiblast, extraembryonic ectoderm, and visceral endoderm) 973:1053 Disruption of Pofut2 using the knockout (LoxP) or gene trap (RST434) allele, as well as deletion of Adamts9, resulted in disorganized epithelia (epiblast, extraembryonic ectoderm, and visceral endoderm) and blocked mesoderm formation during gastrulation. 27297885 1 23 theme Protein 119:125 arg1 O-fucosyltransferase 127:146 Protein O-fucosyltransferase 2 119:148 Protein O-fucosyltransferase 2 (POFUT2) 119:157 Protein O-fucosyltransferase 2 (POFUT2) adds O-linked fucose to Thrombospondin Type 1 Repeats (TSR) in 49 potential target proteins. 27297885 1 23 theme Protein 119:125 arg1 POFUT2 151:156 POFUT2 151:156 POFUT2 151:156 Protein O-fucosyltransferase 2 (POFUT2) adds O-linked fucose to Thrombospondin Type 1 Repeats (TSR) in 49 potential target proteins. 27297885 9 24 theme gastrulation 1723:1734 arg1 defects 1736:1742 the gastrulation defects 1719:1742 the gastrulation defects 1719:1742 Conditional deletion of either Pofut2 or Adamts9 in the epiblast rescues the gastrulation defects, and identified a new role for O-fucosylated ADAMTS9 during morphogenesis of the amnion and axial mesendoderm. 27297885 0 25 theme ADAMTS9 100:106 arg1 secretion 108:116 ADAMTS9 secretion 100:116 ADAMTS9 secretion 100:116 Genetic and biochemical evidence that gastrulation defects in Pofut2 mutants result from defects in ADAMTS9 secretion. 27297885 13 26 theme extracellular 2472:2484 arg1 matrix 2486:2491 the extracellular matrix 2468:2491 the extracellular matrix 2468:2491 In the future, the Pofut2 and Adamts9 knockouts will be valuable tools for understanding how local changes in the properties of the extracellular matrix influence the organization of tissues during mammalian development. 27297885 3 27 theme early 507:511 arg1 lethality 523:531 early embryonic lethality 507:531 early embryonic lethality 507:531 Both the mouse Pofut2 RST434 gene trap allele and the Adamts9 knockout were reported to result in early embryonic lethality, suggesting that defects in Pofut2 mutant embryos could result from loss of O-fucosylation on ADAMTS9. 27297885 6 28 located observed 1253:1260 arg1 mutants 1272:1278 Pofut2 mutants 1265:1278 Pofut2 mutants 1265:1278 The similarity between Pofut2 and Adamts9 mutants suggested that disruption of ADAMTS9 function could be responsible for the gastrulation defects observed in Pofut2 mutants. 27297885 6 28 located observed 1253:1260 arg2 defects 1245:1251 the gastrulation defects 1228:1251 the gastrulation defects observed in Pofut2 mutants 1228:1278 The similarity between Pofut2 and Adamts9 mutants suggested that disruption of ADAMTS9 function could be responsible for the gastrulation defects observed in Pofut2 mutants. 27297885 0 29 from defects 89:95 arg1 secretion 108:116 ADAMTS9 secretion 100:116 ADAMTS9 secretion 100:116 Genetic and biochemical evidence that gastrulation defects in Pofut2 mutants result from defects in ADAMTS9 secretion. 27297885 2 30 theme proteins 399:406 arg1 family 389:394 the A Disintegrin and Metalloprotease with ThromboSpondin type-1 motifs (ADAMTS) or ADAMTS-like family 293:394 family 389:394 Nearly half the POFUT2 targets belong to the A Disintegrin and Metalloprotease with ThromboSpondin type-1 motifs (ADAMTS) or ADAMTS-like family of proteins. 27297885 2 30 theme proteins 399:406 arg1 ADAMTS 366:371 the A Disintegrin and Metalloprotease with ThromboSpondin type-1 motifs (ADAMTS) or ADAMTS-like family 293:394 ADAMTS 366:371 Nearly half the POFUT2 targets belong to the A Disintegrin and Metalloprotease with ThromboSpondin type-1 motifs (ADAMTS) or ADAMTS-like family of proteins. 27297885 2 31 dep half 259:262 arg1 targets 275:281 the POFUT2 targets 264:281 Nearly half the POFUT2 targets 252:281 Nearly half the POFUT2 targets belong to the A Disintegrin and Metalloprotease with ThromboSpondin type-1 motifs (ADAMTS) or ADAMTS-like family of proteins. 27297885 10 32 theme knockout 2003:2010 arg1 Pofut2 1996:2001 the Pofut2 knockout 1992:2010 the Pofut2 knockout 1992:2010 Combined, these results suggested that loss of ADAMTS9 function in the extra embryonic tissue is responsible for gastrulation defects in the Pofut2 knockout. 27297885 0 33 theme Pofut2 62:67 arg1 mutants 69:75 Pofut2 mutants 62:75 Pofut2 mutants 62:75 Genetic and biochemical evidence that gastrulation defects in Pofut2 mutants result from defects in ADAMTS9 secretion. 27297885 9 34 gly O-fucosylated 1775:1787 arg1 ADAMTS9 1789:1795 O-fucosylated ADAMTS9 1775:1795 O-fucosylated ADAMTS9 1775:1795 Conditional deletion of either Pofut2 or Adamts9 in the epiblast rescues the gastrulation defects, and identified a new role for O-fucosylated ADAMTS9 during morphogenesis of the amnion and axial mesendoderm. 27297885 8 35 theme trophoblast 1474:1484 arg1 cells 1492:1496 trophoblast giant cells 1474:1496 trophoblast giant cells 1474:1496 We determined that Adamts9 was dynamically expressed during mouse gastrulation by trophoblast giant cells, parietal endoderm, the most proximal visceral endoderm adjacent to the ectoplacental cone, extraembryonic mesoderm, and anterior primitive streak. 27297885 8 35 theme trophoblast 1474:1484 arg1 endoderm 1508:1515 parietal endoderm 1499:1515 parietal endoderm 1499:1515 We determined that Adamts9 was dynamically expressed during mouse gastrulation by trophoblast giant cells, parietal endoderm, the most proximal visceral endoderm adjacent to the ectoplacental cone, extraembryonic mesoderm, and anterior primitive streak. 27297885 8 35 theme trophoblast 1474:1484 arg1 streak 1638:1643 anterior primitive streak 1619:1643 anterior primitive streak 1619:1643 We determined that Adamts9 was dynamically expressed during mouse gastrulation by trophoblast giant cells, parietal endoderm, the most proximal visceral endoderm adjacent to the ectoplacental cone, extraembryonic mesoderm, and anterior primitive streak. 27297885 8 35 theme trophoblast 1474:1484 arg1 endoderm 1545:1552 the most proximal visceral endoderm 1518:1552 the most proximal visceral endoderm adjacent to the ectoplacental cone 1518:1587 We determined that Adamts9 was dynamically expressed during mouse gastrulation by trophoblast giant cells, parietal endoderm, the most proximal visceral endoderm adjacent to the ectoplacental cone, extraembryonic mesoderm, and anterior primitive streak. 27297885 8 35 theme trophoblast 1474:1484 arg1 mesoderm 1605:1612 extraembryonic mesoderm 1590:1612 extraembryonic mesoderm 1590:1612 We determined that Adamts9 was dynamically expressed during mouse gastrulation by trophoblast giant cells, parietal endoderm, the most proximal visceral endoderm adjacent to the ectoplacental cone, extraembryonic mesoderm, and anterior primitive streak. 27297885 5 36 theme mesoderm 1067:1074 arg1 formation 1076:1084 mesoderm formation 1067:1084 mesoderm formation 1067:1084 Disruption of Pofut2 using the knockout (LoxP) or gene trap (RST434) allele, as well as deletion of Adamts9, resulted in disorganized epithelia (epiblast, extraembryonic ectoderm, and visceral endoderm) and blocked mesoderm formation during gastrulation. 27297885 9 37 theme new 1762:1764 arg1 role 1766:1769 a new role 1760:1769 a new role for O-fucosylated ADAMTS9 during morphogenesis of the amnion and axial mesendoderm 1760:1852 Conditional deletion of either Pofut2 or Adamts9 in the epiblast rescues the gastrulation defects, and identified a new role for O-fucosylated ADAMTS9 during morphogenesis of the amnion and axial mesendoderm. 27297885 4 38 theme Cre-mediated 726:737 arg1 deletion 739:746 Cre-mediated deletion 726:746 Cre-mediated deletion of Pofut2 and Adamts9 726:768 To address this question, we compared the Pofut2 and Adamts9 knockout phenotypes and used Cre-mediated deletion of Pofut2 and Adamts9 to dissect the tissue-specific role of O-fucosylated ADAMTS9 during gastrulation. 27297885 13 39 from changes 2439:2445 arg1 properties 2454:2463 the properties 2450:2463 the properties of the extracellular matrix 2450:2491 In the future, the Pofut2 and Adamts9 knockouts will be valuable tools for understanding how local changes in the properties of the extracellular matrix influence the organization of tissues during mammalian development. 27297885 0 40 from defects 51:57 arg1 mutants 69:75 Pofut2 mutants 62:75 Pofut2 mutants 62:75 Genetic and biochemical evidence that gastrulation defects in Pofut2 mutants result from defects in ADAMTS9 secretion. 27297885 5 41 dep epithelia 986:994 arg1 endoderm 1045:1052 visceral endoderm 1036:1052 visceral endoderm 1036:1052 Disruption of Pofut2 using the knockout (LoxP) or gene trap (RST434) allele, as well as deletion of Adamts9, resulted in disorganized epithelia (epiblast, extraembryonic ectoderm, and visceral endoderm) and blocked mesoderm formation during gastrulation. 27297885 5 41 dep epithelia 986:994 arg1 epiblast 997:1004 epiblast 997:1004 epiblast 997:1004 Disruption of Pofut2 using the knockout (LoxP) or gene trap (RST434) allele, as well as deletion of Adamts9, resulted in disorganized epithelia (epiblast, extraembryonic ectoderm, and visceral endoderm) and blocked mesoderm formation during gastrulation. 27297885 5 41 dep epithelia 986:994 arg1 ectoderm 1022:1029 extraembryonic ectoderm 1007:1029 extraembryonic ectoderm 1007:1029 Disruption of Pofut2 using the knockout (LoxP) or gene trap (RST434) allele, as well as deletion of Adamts9, resulted in disorganized epithelia (epiblast, extraembryonic ectoderm, and visceral endoderm) and blocked mesoderm formation during gastrulation. 27297885 7 42 from knockout 1326:1333 arg1 cells 1356:1360 HEK293T cells 1348:1360 HEK293T cells 1348:1360 Consistent with this prediction, CRISPR/Cas9 knockout of POFUT2 in HEK293T cells blocked secretion of ADAMTS9. 27297885 1 43 link O-linked 164:171 arg1 fucose 173:178 O-linked fucose 164:178 O-linked fucose 164:178 Protein O-fucosyltransferase 2 (POFUT2) adds O-linked fucose to Thrombospondin Type 1 Repeats (TSR) in 49 potential target proteins. 27297885 4 44 theme knockout 697:704 arg1 phenotypes 706:715 the Pofut2 and Adamts9 knockout phenotypes 674:715 the Pofut2 and Adamts9 knockout phenotypes 674:715 To address this question, we compared the Pofut2 and Adamts9 knockout phenotypes and used Cre-mediated deletion of Pofut2 and Adamts9 to dissect the tissue-specific role of O-fucosylated ADAMTS9 during gastrulation. 27297885 0 45 theme Genetic 0:6 arg1 evidence 24:31 Genetic and biochemical evidence 0:31 Genetic and biochemical evidence that gastrulation defects in Pofut2 mutants 0:75 Genetic and biochemical evidence that gastrulation defects in Pofut2 mutants result from defects in ADAMTS9 secretion. 27297885 5 46 theme trap 907:910 arg1 allele 921:926 the knockout (LoxP) or gene trap (RST434) allele 879:926 allele 921:926 Disruption of Pofut2 using the knockout (LoxP) or gene trap (RST434) allele, as well as deletion of Adamts9, resulted in disorganized epithelia (epiblast, extraembryonic ectoderm, and visceral endoderm) and blocked mesoderm formation during gastrulation. 27297885 11 47 theme altered 2144:2150 arg1 characteristics 2152:2166 altered characteristics 2144:2166 altered characteristics of the extraembryonic ectoderm 2144:2197 We hypothesize that loss of ADAMTS9 function in the most proximal visceral endoderm leads to slippage of the visceral endoderm and altered characteristics of the extraembryonic ectoderm. 27297885 12 48 theme input 2222:2226 arg1 loss 2214:2217 loss 2214:2217 loss of input from the extraembryonic ectoderm and/or compression of the epiblast by Reichert's membrane 2214:2317 Consequently, loss of input from the extraembryonic ectoderm and/or compression of the epiblast by Reichert's membrane blocks gastrulation. 27297885 3 49 theme gene 438:441 arg1 allele 448:453 the mouse Pofut2 RST434 gene trap allele 414:453 the mouse Pofut2 RST434 gene trap allele 414:453 Both the mouse Pofut2 RST434 gene trap allele and the Adamts9 knockout were reported to result in early embryonic lethality, suggesting that defects in Pofut2 mutant embryos could result from loss of O-fucosylation on ADAMTS9. 27297885 0 50 theme biochemical 12:22 arg1 evidence 24:31 Genetic and biochemical evidence 0:31 Genetic and biochemical evidence that gastrulation defects in Pofut2 mutants 0:75 Genetic and biochemical evidence that gastrulation defects in Pofut2 mutants result from defects in ADAMTS9 secretion. 27297885 2 51 with Disintegrin 299:309 arg1 motifs 358:363 ThromboSpondin type-1 motifs 336:363 ThromboSpondin type-1 motifs 336:363 Nearly half the POFUT2 targets belong to the A Disintegrin and Metalloprotease with ThromboSpondin type-1 motifs (ADAMTS) or ADAMTS-like family of proteins. 27297885 5 52 theme RST434 913:918 arg1 allele 921:926 the knockout (LoxP) or gene trap (RST434) allele 879:926 allele 921:926 Disruption of Pofut2 using the knockout (LoxP) or gene trap (RST434) allele, as well as deletion of Adamts9, resulted in disorganized epithelia (epiblast, extraembryonic ectoderm, and visceral endoderm) and blocked mesoderm formation during gastrulation. 27297885 12 53 dep ectoderm 2252:2259 arg1 the 2233:2235 the 2233:2235 the 2233:2235 Consequently, loss of input from the extraembryonic ectoderm and/or compression of the epiblast by Reichert's membrane blocks gastrulation. 27297885 8 54 theme visceral 1536:1543 arg1 cells 1492:1496 trophoblast giant cells 1474:1496 trophoblast giant cells 1474:1496 We determined that Adamts9 was dynamically expressed during mouse gastrulation by trophoblast giant cells, parietal endoderm, the most proximal visceral endoderm adjacent to the ectoplacental cone, extraembryonic mesoderm, and anterior primitive streak. 27297885 8 54 theme visceral 1536:1543 arg1 endoderm 1545:1552 the most proximal visceral endoderm 1518:1552 the most proximal visceral endoderm adjacent to the ectoplacental cone 1518:1587 We determined that Adamts9 was dynamically expressed during mouse gastrulation by trophoblast giant cells, parietal endoderm, the most proximal visceral endoderm adjacent to the ectoplacental cone, extraembryonic mesoderm, and anterior primitive streak. 27297885 3 55 theme Pofut2 424:429 arg1 allele 448:453 the mouse Pofut2 RST434 gene trap allele 414:453 the mouse Pofut2 RST434 gene trap allele 414:453 Both the mouse Pofut2 RST434 gene trap allele and the Adamts9 knockout were reported to result in early embryonic lethality, suggesting that defects in Pofut2 mutant embryos could result from loss of O-fucosylation on ADAMTS9. 27297885 2 56 with Metalloprotease 315:329 arg1 motifs 358:363 ThromboSpondin type-1 motifs 336:363 ThromboSpondin type-1 motifs 336:363 Nearly half the POFUT2 targets belong to the A Disintegrin and Metalloprotease with ThromboSpondin type-1 motifs (ADAMTS) or ADAMTS-like family of proteins. 27297885 11 57 theme extraembryonic 2175:2188 arg1 ectoderm 2190:2197 the extraembryonic ectoderm 2171:2197 the extraembryonic ectoderm 2171:2197 We hypothesize that loss of ADAMTS9 function in the most proximal visceral endoderm leads to slippage of the visceral endoderm and altered characteristics of the extraembryonic ectoderm. 27297885 8 58 theme adjacent 1554:1561 arg1 cells 1492:1496 trophoblast giant cells 1474:1496 trophoblast giant cells 1474:1496 We determined that Adamts9 was dynamically expressed during mouse gastrulation by trophoblast giant cells, parietal endoderm, the most proximal visceral endoderm adjacent to the ectoplacental cone, extraembryonic mesoderm, and anterior primitive streak. 27297885 8 58 theme adjacent 1554:1561 arg1 endoderm 1545:1552 the most proximal visceral endoderm 1518:1552 the most proximal visceral endoderm adjacent to the ectoplacental cone 1518:1587 We determined that Adamts9 was dynamically expressed during mouse gastrulation by trophoblast giant cells, parietal endoderm, the most proximal visceral endoderm adjacent to the ectoplacental cone, extraembryonic mesoderm, and anterior primitive streak. 27297885 11 59 theme visceral 2122:2129 arg1 endoderm 2131:2138 the visceral endoderm 2118:2138 the visceral endoderm 2118:2138 We hypothesize that loss of ADAMTS9 function in the most proximal visceral endoderm leads to slippage of the visceral endoderm and altered characteristics of the extraembryonic ectoderm. 27297885 2 60 theme Metalloprotease 315:329 arg1 ADAMTS 366:371 the A Disintegrin and Metalloprotease with ThromboSpondin type-1 motifs (ADAMTS) or ADAMTS-like family 293:394 ADAMTS 366:371 Nearly half the POFUT2 targets belong to the A Disintegrin and Metalloprotease with ThromboSpondin type-1 motifs (ADAMTS) or ADAMTS-like family of proteins. 27297885 13 61 theme valuable 2396:2403 arg1 tools 2405:2409 valuable tools 2396:2409 valuable tools for understanding how local changes in the properties of the extracellular matrix influence the organization of tissues during mammalian development 2396:2558 In the future, the Pofut2 and Adamts9 knockouts will be valuable tools for understanding how local changes in the properties of the extracellular matrix influence the organization of tissues during mammalian development. 27297885 13 61 theme valuable 2396:2403 arg1 knockouts 2378:2386 the Pofut2 and Adamts9 knockouts 2355:2386 the Pofut2 and Adamts9 knockouts 2355:2386 In the future, the Pofut2 and Adamts9 knockouts will be valuable tools for understanding how local changes in the properties of the extracellular matrix influence the organization of tissues during mammalian development. 27297885 9 62 theme mesendoderm 1842:1852 arg1 morphogenesis 1804:1816 morphogenesis 1804:1816 morphogenesis of the amnion and axial mesendoderm 1804:1852 Conditional deletion of either Pofut2 or Adamts9 in the epiblast rescues the gastrulation defects, and identified a new role for O-fucosylated ADAMTS9 during morphogenesis of the amnion and axial mesendoderm. 27297885 2 63 theme Disintegrin 299:309 arg1 ADAMTS 366:371 the A Disintegrin and Metalloprotease with ThromboSpondin type-1 motifs (ADAMTS) or ADAMTS-like family 293:394 ADAMTS 366:371 Nearly half the POFUT2 targets belong to the A Disintegrin and Metalloprotease with ThromboSpondin type-1 motifs (ADAMTS) or ADAMTS-like family of proteins. 27297885 13 64 theme Pofut2 2359:2364 arg1 tools 2405:2409 valuable tools 2396:2409 valuable tools for understanding how local changes in the properties of the extracellular matrix influence the organization of tissues during mammalian development 2396:2558 In the future, the Pofut2 and Adamts9 knockouts will be valuable tools for understanding how local changes in the properties of the extracellular matrix influence the organization of tissues during mammalian development. 27297885 13 64 theme Pofut2 2359:2364 arg1 knockouts 2378:2386 the Pofut2 and Adamts9 knockouts 2355:2386 the Pofut2 and Adamts9 knockouts 2355:2386 In the future, the Pofut2 and Adamts9 knockouts will be valuable tools for understanding how local changes in the properties of the extracellular matrix influence the organization of tissues during mammalian development. 27297885 11 65 from loss 2033:2036 arg1 endoderm 2088:2095 the most proximal visceral endoderm 2061:2095 the most proximal visceral endoderm 2061:2095 We hypothesize that loss of ADAMTS9 function in the most proximal visceral endoderm leads to slippage of the visceral endoderm and altered characteristics of the extraembryonic ectoderm. 27297885 2 66 theme ADAMTS-like 377:387 arg1 family 389:394 the A Disintegrin and Metalloprotease with ThromboSpondin type-1 motifs (ADAMTS) or ADAMTS-like family 293:394 family 389:394 Nearly half the POFUT2 targets belong to the A Disintegrin and Metalloprotease with ThromboSpondin type-1 motifs (ADAMTS) or ADAMTS-like family of proteins. 27297885 13 67 theme Adamts9 2370:2376 arg1 tools 2405:2409 valuable tools 2396:2409 valuable tools for understanding how local changes in the properties of the extracellular matrix influence the organization of tissues during mammalian development 2396:2558 In the future, the Pofut2 and Adamts9 knockouts will be valuable tools for understanding how local changes in the properties of the extracellular matrix influence the organization of tissues during mammalian development. 27297885 13 67 theme Adamts9 2370:2376 arg1 knockouts 2378:2386 the Pofut2 and Adamts9 knockouts 2355:2386 the Pofut2 and Adamts9 knockouts 2355:2386 In the future, the Pofut2 and Adamts9 knockouts will be valuable tools for understanding how local changes in the properties of the extracellular matrix influence the organization of tissues during mammalian development. 27297885 8 68 theme extraembryonic 1590:1603 arg1 cells 1492:1496 trophoblast giant cells 1474:1496 trophoblast giant cells 1474:1496 We determined that Adamts9 was dynamically expressed during mouse gastrulation by trophoblast giant cells, parietal endoderm, the most proximal visceral endoderm adjacent to the ectoplacental cone, extraembryonic mesoderm, and anterior primitive streak. 27297885 8 68 theme extraembryonic 1590:1603 arg1 mesoderm 1605:1612 extraembryonic mesoderm 1590:1612 extraembryonic mesoderm 1590:1612 We determined that Adamts9 was dynamically expressed during mouse gastrulation by trophoblast giant cells, parietal endoderm, the most proximal visceral endoderm adjacent to the ectoplacental cone, extraembryonic mesoderm, and anterior primitive streak. 27297885 10 69 theme ADAMTS9 1902:1908 arg1 function 1910:1917 ADAMTS9 function 1902:1917 ADAMTS9 function 1902:1917 Combined, these results suggested that loss of ADAMTS9 function in the extra embryonic tissue is responsible for gastrulation defects in the Pofut2 knockout. 27297885 2 70 theme ThromboSpondin 336:349 arg1 motifs 358:363 ThromboSpondin type-1 motifs 336:363 ThromboSpondin type-1 motifs 336:363 Nearly half the POFUT2 targets belong to the A Disintegrin and Metalloprotease with ThromboSpondin type-1 motifs (ADAMTS) or ADAMTS-like family of proteins. 27297885 1 71 theme potential 225:233 arg1 proteins 242:249 49 potential target proteins 222:249 49 potential target proteins 222:249 Protein O-fucosyltransferase 2 (POFUT2) adds O-linked fucose to Thrombospondin Type 1 Repeats (TSR) in 49 potential target proteins. 27297885 12 72 theme epiblast 2287:2294 arg1 ectoderm 2252:2259 extraembryonic ectoderm 2237:2259 extraembryonic ectoderm 2237:2259 Consequently, loss of input from the extraembryonic ectoderm and/or compression of the epiblast by Reichert's membrane blocks gastrulation. 27297885 11 73 theme endoderm 2131:2138 arg1 slippage 2106:2113 slippage 2106:2113 slippage of the visceral endoderm 2106:2138 We hypothesize that loss of ADAMTS9 function in the most proximal visceral endoderm leads to slippage of the visceral endoderm and altered characteristics of the extraembryonic ectoderm. 27297885 11 73 theme endoderm 2131:2138 arg1 characteristics 2152:2166 altered characteristics 2144:2166 altered characteristics of the extraembryonic ectoderm 2144:2197 We hypothesize that loss of ADAMTS9 function in the most proximal visceral endoderm leads to slippage of the visceral endoderm and altered characteristics of the extraembryonic ectoderm. 27297885 3 74 from loss 601:604 arg1 ADAMTS9 627:633 ADAMTS9 627:633 ADAMTS9 627:633 Both the mouse Pofut2 RST434 gene trap allele and the Adamts9 knockout were reported to result in early embryonic lethality, suggesting that defects in Pofut2 mutant embryos could result from loss of O-fucosylation on ADAMTS9. 27297885 6 75 theme gastrulation 1232:1243 arg1 defects 1245:1251 the gastrulation defects 1228:1251 the gastrulation defects observed in Pofut2 mutants 1228:1278 The similarity between Pofut2 and Adamts9 mutants suggested that disruption of ADAMTS9 function could be responsible for the gastrulation defects observed in Pofut2 mutants. 27297885 2 76 theme POFUT2 268:273 arg1 targets 275:281 the POFUT2 targets 264:281 Nearly half the POFUT2 targets 252:281 Nearly half the POFUT2 targets belong to the A Disintegrin and Metalloprotease with ThromboSpondin type-1 motifs (ADAMTS) or ADAMTS-like family of proteins. 27297885 8 77 theme anterior 1619:1626 arg1 cells 1492:1496 trophoblast giant cells 1474:1496 trophoblast giant cells 1474:1496 We determined that Adamts9 was dynamically expressed during mouse gastrulation by trophoblast giant cells, parietal endoderm, the most proximal visceral endoderm adjacent to the ectoplacental cone, extraembryonic mesoderm, and anterior primitive streak. 27297885 8 77 theme anterior 1619:1626 arg1 streak 1638:1643 anterior primitive streak 1619:1643 anterior primitive streak 1619:1643 We determined that Adamts9 was dynamically expressed during mouse gastrulation by trophoblast giant cells, parietal endoderm, the most proximal visceral endoderm adjacent to the ectoplacental cone, extraembryonic mesoderm, and anterior primitive streak. 27297885 10 78 theme extra 1926:1930 arg1 tissue 1942:1947 the extra embryonic tissue 1922:1947 the extra embryonic tissue 1922:1947 Combined, these results suggested that loss of ADAMTS9 function in the extra embryonic tissue is responsible for gastrulation defects in the Pofut2 knockout. 27297885 1 79 theme O-linked 164:171 arg1 fucose 173:178 O-linked fucose 164:178 O-linked fucose 164:178 Protein O-fucosyltransferase 2 (POFUT2) adds O-linked fucose to Thrombospondin Type 1 Repeats (TSR) in 49 potential target proteins. 27297885 11 80 theme ectoderm 2190:2197 arg1 slippage 2106:2113 slippage 2106:2113 slippage of the visceral endoderm 2106:2138 We hypothesize that loss of ADAMTS9 function in the most proximal visceral endoderm leads to slippage of the visceral endoderm and altered characteristics of the extraembryonic ectoderm. 27297885 11 80 theme ectoderm 2190:2197 arg1 characteristics 2152:2166 altered characteristics 2144:2166 altered characteristics of the extraembryonic ectoderm 2144:2197 We hypothesize that loss of ADAMTS9 function in the most proximal visceral endoderm leads to slippage of the visceral endoderm and altered characteristics of the extraembryonic ectoderm. 27297885 10 81 from loss 1894:1897 arg1 tissue 1942:1947 the extra embryonic tissue 1922:1947 the extra embryonic tissue 1922:1947 Combined, these results suggested that loss of ADAMTS9 function in the extra embryonic tissue is responsible for gastrulation defects in the Pofut2 knockout. 27297885 4 82 theme ADAMTS9 823:829 arg1 role 801:804 the tissue-specific role 781:804 the tissue-specific role of O-fucosylated ADAMTS9 during gastrulation 781:849 To address this question, we compared the Pofut2 and Adamts9 knockout phenotypes and used Cre-mediated deletion of Pofut2 and Adamts9 to dissect the tissue-specific role of O-fucosylated ADAMTS9 during gastrulation. 27297885 7 83 theme ADAMTS9 1383:1389 arg1 secretion 1370:1378 secretion 1370:1378 secretion of ADAMTS9 1370:1389 Consistent with this prediction, CRISPR/Cas9 knockout of POFUT2 in HEK293T cells blocked secretion of ADAMTS9. 27297885 13 84 theme matrix 2486:2491 arg1 properties 2454:2463 the properties 2450:2463 the properties of the extracellular matrix 2450:2491 In the future, the Pofut2 and Adamts9 knockouts will be valuable tools for understanding how local changes in the properties of the extracellular matrix influence the organization of tissues during mammalian development. 27297885 1 85 theme Type 198:201 arg1 TSR 214:216 TSR 214:216 TSR 214:216 Protein O-fucosyltransferase 2 (POFUT2) adds O-linked fucose to Thrombospondin Type 1 Repeats (TSR) in 49 potential target proteins. 27297885 1 85 theme Type 198:201 arg1 Repeats 205:211 Thrombospondin Type 1 Repeats 183:211 Thrombospondin Type 1 Repeats (TSR) in 49 potential target proteins 183:249 Protein O-fucosyltransferase 2 (POFUT2) adds O-linked fucose to Thrombospondin Type 1 Repeats (TSR) in 49 potential target proteins. 27297885 3 86 theme knockout 471:478 arg1 Adamts9 463:469 the Adamts9 knockout 459:478 the Adamts9 knockout 459:478 Both the mouse Pofut2 RST434 gene trap allele and the Adamts9 knockout were reported to result in early embryonic lethality, suggesting that defects in Pofut2 mutant embryos could result from loss of O-fucosylation on ADAMTS9. 27297885 5 87 theme extraembryonic 1007:1020 arg1 ectoderm 1022:1029 extraembryonic ectoderm 1007:1029 extraembryonic ectoderm 1007:1029 Disruption of Pofut2 using the knockout (LoxP) or gene trap (RST434) allele, as well as deletion of Adamts9, resulted in disorganized epithelia (epiblast, extraembryonic ectoderm, and visceral endoderm) and blocked mesoderm formation during gastrulation. 27297885 3 88 theme Pofut2 561:566 arg1 embryos 575:581 Pofut2 mutant embryos 561:581 Pofut2 mutant embryos 561:581 Both the mouse Pofut2 RST434 gene trap allele and the Adamts9 knockout were reported to result in early embryonic lethality, suggesting that defects in Pofut2 mutant embryos could result from loss of O-fucosylation on ADAMTS9. 27297885 11 89 theme function 2049:2056 arg1 loss 2033:2036 loss 2033:2036 loss of ADAMTS9 function in the most proximal visceral endoderm 2033:2095 We hypothesize that loss of ADAMTS9 function in the most proximal visceral endoderm leads to slippage of the visceral endoderm and altered characteristics of the extraembryonic ectoderm. 27297885 6 90 theme ADAMTS9 1186:1192 arg1 function 1194:1201 ADAMTS9 function 1186:1201 ADAMTS9 function 1186:1201 The similarity between Pofut2 and Adamts9 mutants suggested that disruption of ADAMTS9 function could be responsible for the gastrulation defects observed in Pofut2 mutants. 27297885 6 91 dep Pofut2 1130:1135 arg1 mutants 1149:1155 mutants 1149:1155 mutants 1149:1155 The similarity between Pofut2 and Adamts9 mutants suggested that disruption of ADAMTS9 function could be responsible for the gastrulation defects observed in Pofut2 mutants. 27297885 7 92 with Consistent 1281:1290 arg1 prediction 1302:1311 this prediction 1297:1311 this prediction 1297:1311 Consistent with this prediction, CRISPR/Cas9 knockout of POFUT2 in HEK293T cells blocked secretion of ADAMTS9. 27297885 8 93 theme mouse 1452:1456 arg1 gastrulation 1458:1469 mouse gastrulation 1452:1469 mouse gastrulation 1452:1469 We determined that Adamts9 was dynamically expressed during mouse gastrulation by trophoblast giant cells, parietal endoderm, the most proximal visceral endoderm adjacent to the ectoplacental cone, extraembryonic mesoderm, and anterior primitive streak. 27297885 10 94 theme gastrulation 1968:1979 arg1 defects 1981:1987 gastrulation defects 1968:1987 gastrulation defects in the Pofut2 knockout 1968:2010 Combined, these results suggested that loss of ADAMTS9 function in the extra embryonic tissue is responsible for gastrulation defects in the Pofut2 knockout. 27297885 6 95 theme Pofut2 1265:1270 arg1 mutants 1272:1278 Pofut2 mutants 1265:1278 Pofut2 mutants 1265:1278 The similarity between Pofut2 and Adamts9 mutants suggested that disruption of ADAMTS9 function could be responsible for the gastrulation defects observed in Pofut2 mutants. 27297885 11 96 theme proximal 2070:2077 arg1 endoderm 2088:2095 the most proximal visceral endoderm 2061:2095 the most proximal visceral endoderm 2061:2095 We hypothesize that loss of ADAMTS9 function in the most proximal visceral endoderm leads to slippage of the visceral endoderm and altered characteristics of the extraembryonic ectoderm. 27297885 4 97 theme Pofut2 678:683 arg1 phenotypes 706:715 the Pofut2 and Adamts9 knockout phenotypes 674:715 the Pofut2 and Adamts9 knockout phenotypes 674:715 To address this question, we compared the Pofut2 and Adamts9 knockout phenotypes and used Cre-mediated deletion of Pofut2 and Adamts9 to dissect the tissue-specific role of O-fucosylated ADAMTS9 during gastrulation. 27297885 13 98 from tools 2405:2409 arg1 future 2347:2352 future 2347:2352 future 2347:2352 In the future, the Pofut2 and Adamts9 knockouts will be valuable tools for understanding how local changes in the properties of the extracellular matrix influence the organization of tissues during mammalian development. 27297885 5 99 theme Pofut2 866:871 arg1 deletion 940:947 deletion 940:947 deletion of Adamts9 940:958 Disruption of Pofut2 using the knockout (LoxP) or gene trap (RST434) allele, as well as deletion of Adamts9, resulted in disorganized epithelia (epiblast, extraembryonic ectoderm, and visceral endoderm) and blocked mesoderm formation during gastrulation. 27297885 5 99 theme Pofut2 866:871 arg1 Disruption 852:861 Disruption 852:861 Disruption 852:861 Disruption of Pofut2 using the knockout (LoxP) or gene trap (RST434) allele, as well as deletion of Adamts9, resulted in disorganized epithelia (epiblast, extraembryonic ectoderm, and visceral endoderm) and blocked mesoderm formation during gastrulation. 27297885 8 100 theme giant 1486:1490 arg1 cells 1492:1496 trophoblast giant cells 1474:1496 trophoblast giant cells 1474:1496 We determined that Adamts9 was dynamically expressed during mouse gastrulation by trophoblast giant cells, parietal endoderm, the most proximal visceral endoderm adjacent to the ectoplacental cone, extraembryonic mesoderm, and anterior primitive streak. 27297885 8 100 theme giant 1486:1490 arg1 endoderm 1508:1515 parietal endoderm 1499:1515 parietal endoderm 1499:1515 We determined that Adamts9 was dynamically expressed during mouse gastrulation by trophoblast giant cells, parietal endoderm, the most proximal visceral endoderm adjacent to the ectoplacental cone, extraembryonic mesoderm, and anterior primitive streak. 27297885 8 100 theme giant 1486:1490 arg1 streak 1638:1643 anterior primitive streak 1619:1643 anterior primitive streak 1619:1643 We determined that Adamts9 was dynamically expressed during mouse gastrulation by trophoblast giant cells, parietal endoderm, the most proximal visceral endoderm adjacent to the ectoplacental cone, extraembryonic mesoderm, and anterior primitive streak. 27297885 8 100 theme giant 1486:1490 arg1 endoderm 1545:1552 the most proximal visceral endoderm 1518:1552 the most proximal visceral endoderm adjacent to the ectoplacental cone 1518:1587 We determined that Adamts9 was dynamically expressed during mouse gastrulation by trophoblast giant cells, parietal endoderm, the most proximal visceral endoderm adjacent to the ectoplacental cone, extraembryonic mesoderm, and anterior primitive streak. 27297885 8 100 theme giant 1486:1490 arg1 mesoderm 1605:1612 extraembryonic mesoderm 1590:1612 extraembryonic mesoderm 1590:1612 We determined that Adamts9 was dynamically expressed during mouse gastrulation by trophoblast giant cells, parietal endoderm, the most proximal visceral endoderm adjacent to the ectoplacental cone, extraembryonic mesoderm, and anterior primitive streak. 27297885 13 101 theme local 2433:2437 arg1 changes 2439:2445 local changes 2433:2445 local changes in the properties of the extracellular matrix 2433:2491 In the future, the Pofut2 and Adamts9 knockouts will be valuable tools for understanding how local changes in the properties of the extracellular matrix influence the organization of tissues during mammalian development. 27297885 12 102 from compression 2268:2278 arg1 input 2222:2226 input 2222:2226 input from the extraembryonic ectoderm and/or compression of the epiblast 2222:2294 Consequently, loss of input from the extraembryonic ectoderm and/or compression of the epiblast by Reichert's membrane blocks gastrulation. 27297885 12 102 from compression 2268:2278 arg1 loss 2214:2217 loss 2214:2217 loss of input from the extraembryonic ectoderm and/or compression of the epiblast by Reichert's membrane 2214:2317 Consequently, loss of input from the extraembryonic ectoderm and/or compression of the epiblast by Reichert's membrane blocks gastrulation. 27297885 5 103 theme visceral 1036:1043 arg1 endoderm 1045:1052 visceral endoderm 1036:1052 visceral endoderm 1036:1052 Disruption of Pofut2 using the knockout (LoxP) or gene trap (RST434) allele, as well as deletion of Adamts9, resulted in disorganized epithelia (epiblast, extraembryonic ectoderm, and visceral endoderm) and blocked mesoderm formation during gastrulation. 27297885 10 104 from defects 1981:1987 arg1 Pofut2 1996:2001 the Pofut2 knockout 1992:2010 the Pofut2 knockout 1992:2010 Combined, these results suggested that loss of ADAMTS9 function in the extra embryonic tissue is responsible for gastrulation defects in the Pofut2 knockout. 27297885 9 105 theme O-fucosylated 1775:1787 arg1 ADAMTS9 1789:1795 O-fucosylated ADAMTS9 1775:1795 O-fucosylated ADAMTS9 1775:1795 Conditional deletion of either Pofut2 or Adamts9 in the epiblast rescues the gastrulation defects, and identified a new role for O-fucosylated ADAMTS9 during morphogenesis of the amnion and axial mesendoderm. 27297885 12 106 theme extraembryonic 2237:2250 arg1 ectoderm 2252:2259 extraembryonic ectoderm 2237:2259 extraembryonic ectoderm 2237:2259 Consequently, loss of input from the extraembryonic ectoderm and/or compression of the epiblast by Reichert's membrane blocks gastrulation. 27297885 3 107 theme mouse 418:422 arg1 allele 448:453 the mouse Pofut2 RST434 gene trap allele 414:453 the mouse Pofut2 RST434 gene trap allele 414:453 Both the mouse Pofut2 RST434 gene trap allele and the Adamts9 knockout were reported to result in early embryonic lethality, suggesting that defects in Pofut2 mutant embryos could result from loss of O-fucosylation on ADAMTS9. 27297885 5 108 theme gene 902:905 arg1 allele 921:926 the knockout (LoxP) or gene trap (RST434) allele 879:926 allele 921:926 Disruption of Pofut2 using the knockout (LoxP) or gene trap (RST434) allele, as well as deletion of Adamts9, resulted in disorganized epithelia (epiblast, extraembryonic ectoderm, and visceral endoderm) and blocked mesoderm formation during gastrulation. 27297885 8 109 theme parietal 1499:1506 arg1 cells 1492:1496 trophoblast giant cells 1474:1496 trophoblast giant cells 1474:1496 We determined that Adamts9 was dynamically expressed during mouse gastrulation by trophoblast giant cells, parietal endoderm, the most proximal visceral endoderm adjacent to the ectoplacental cone, extraembryonic mesoderm, and anterior primitive streak. 27297885 8 109 theme parietal 1499:1506 arg1 endoderm 1508:1515 parietal endoderm 1499:1515 parietal endoderm 1499:1515 We determined that Adamts9 was dynamically expressed during mouse gastrulation by trophoblast giant cells, parietal endoderm, the most proximal visceral endoderm adjacent to the ectoplacental cone, extraembryonic mesoderm, and anterior primitive streak. 27297885 8 110 theme proximal 1527:1534 arg1 cells 1492:1496 trophoblast giant cells 1474:1496 trophoblast giant cells 1474:1496 We determined that Adamts9 was dynamically expressed during mouse gastrulation by trophoblast giant cells, parietal endoderm, the most proximal visceral endoderm adjacent to the ectoplacental cone, extraembryonic mesoderm, and anterior primitive streak. 27297885 8 110 theme proximal 1527:1534 arg1 endoderm 1545:1552 the most proximal visceral endoderm 1518:1552 the most proximal visceral endoderm adjacent to the ectoplacental cone 1518:1587 We determined that Adamts9 was dynamically expressed during mouse gastrulation by trophoblast giant cells, parietal endoderm, the most proximal visceral endoderm adjacent to the ectoplacental cone, extraembryonic mesoderm, and anterior primitive streak. 27297885 4 111 theme Adamts9 689:695 arg1 phenotypes 706:715 the Pofut2 and Adamts9 knockout phenotypes 674:715 the Pofut2 and Adamts9 knockout phenotypes 674:715 To address this question, we compared the Pofut2 and Adamts9 knockout phenotypes and used Cre-mediated deletion of Pofut2 and Adamts9 to dissect the tissue-specific role of O-fucosylated ADAMTS9 during gastrulation. 27297885 3 112 from defects 550:556 arg1 embryos 575:581 Pofut2 mutant embryos 561:581 Pofut2 mutant embryos 561:581 Both the mouse Pofut2 RST434 gene trap allele and the Adamts9 knockout were reported to result in early embryonic lethality, suggesting that defects in Pofut2 mutant embryos could result from loss of O-fucosylation on ADAMTS9. 27297885 7 113 theme HEK293T 1348:1354 arg1 cells 1356:1360 HEK293T cells 1348:1360 HEK293T cells 1348:1360 Consistent with this prediction, CRISPR/Cas9 knockout of POFUT2 in HEK293T cells blocked secretion of ADAMTS9. 27297885 3 114 theme O-fucosylation 609:622 arg1 loss 601:604 loss 601:604 loss of O-fucosylation on ADAMTS9 601:633 Both the mouse Pofut2 RST434 gene trap allele and the Adamts9 knockout were reported to result in early embryonic lethality, suggesting that defects in Pofut2 mutant embryos could result from loss of O-fucosylation on ADAMTS9. 27297885 3 115 theme trap 443:446 arg1 allele 448:453 the mouse Pofut2 RST434 gene trap allele 414:453 the mouse Pofut2 RST434 gene trap allele 414:453 Both the mouse Pofut2 RST434 gene trap allele and the Adamts9 knockout were reported to result in early embryonic lethality, suggesting that defects in Pofut2 mutant embryos could result from loss of O-fucosylation on ADAMTS9. 27297885 0 116 theme gastrulation 38:49 arg1 defects 51:57 gastrulation defects 38:57 gastrulation defects in Pofut2 mutants 38:75 Genetic and biochemical evidence that gastrulation defects in Pofut2 mutants result from defects in ADAMTS9 secretion. 27297885 5 117 theme Adamts9 952:958 arg1 deletion 940:947 deletion 940:947 deletion of Adamts9 940:958 Disruption of Pofut2 using the knockout (LoxP) or gene trap (RST434) allele, as well as deletion of Adamts9, resulted in disorganized epithelia (epiblast, extraembryonic ectoderm, and visceral endoderm) and blocked mesoderm formation during gastrulation. 27297885 5 117 theme Adamts9 952:958 arg1 Disruption 852:861 Disruption 852:861 Disruption 852:861 Disruption of Pofut2 using the knockout (LoxP) or gene trap (RST434) allele, as well as deletion of Adamts9, resulted in disorganized epithelia (epiblast, extraembryonic ectoderm, and visceral endoderm) and blocked mesoderm formation during gastrulation. 27297885 7 118 from cells 1356:1360 arg1 knockout 1326:1333 knockout 1326:1333 knockout 1326:1333 Consistent with this prediction, CRISPR/Cas9 knockout of POFUT2 in HEK293T cells blocked secretion of ADAMTS9. 27297885 9 119 theme amnion 1825:1830 arg1 mesendoderm 1842:1852 the amnion and axial mesendoderm 1821:1852 the amnion and axial mesendoderm 1821:1852 Conditional deletion of either Pofut2 or Adamts9 in the epiblast rescues the gastrulation defects, and identified a new role for O-fucosylated ADAMTS9 during morphogenesis of the amnion and axial mesendoderm. 27297885 3 120 theme RST434 431:436 arg1 allele 448:453 the mouse Pofut2 RST434 gene trap allele 414:453 the mouse Pofut2 RST434 gene trap allele 414:453 Both the mouse Pofut2 RST434 gene trap allele and the Adamts9 knockout were reported to result in early embryonic lethality, suggesting that defects in Pofut2 mutant embryos could result from loss of O-fucosylation on ADAMTS9. 27297885 9 121 theme axial 1836:1840 arg1 mesendoderm 1842:1852 the amnion and axial mesendoderm 1821:1852 the amnion and axial mesendoderm 1821:1852 Conditional deletion of either Pofut2 or Adamts9 in the epiblast rescues the gastrulation defects, and identified a new role for O-fucosylated ADAMTS9 during morphogenesis of the amnion and axial mesendoderm. 27297885 8 122 theme ectoplacental 1570:1582 arg1 cone 1584:1587 the ectoplacental cone 1566:1587 the ectoplacental cone 1566:1587 We determined that Adamts9 was dynamically expressed during mouse gastrulation by trophoblast giant cells, parietal endoderm, the most proximal visceral endoderm adjacent to the ectoplacental cone, extraembryonic mesoderm, and anterior primitive streak. 27297885 4 123 theme tissue-specific 785:799 arg1 role 801:804 the tissue-specific role 781:804 the tissue-specific role of O-fucosylated ADAMTS9 during gastrulation 781:849 To address this question, we compared the Pofut2 and Adamts9 knockout phenotypes and used Cre-mediated deletion of Pofut2 and Adamts9 to dissect the tissue-specific role of O-fucosylated ADAMTS9 during gastrulation. 27297885 4 124 theme Pofut2 751:756 arg1 deletion 739:746 Cre-mediated deletion 726:746 Cre-mediated deletion of Pofut2 and Adamts9 726:768 To address this question, we compared the Pofut2 and Adamts9 knockout phenotypes and used Cre-mediated deletion of Pofut2 and Adamts9 to dissect the tissue-specific role of O-fucosylated ADAMTS9 during gastrulation. 27297885 4 125 used used 721:724 arg2 we 662:663 we 662:663 we 662:663 To address this question, we compared the Pofut2 and Adamts9 knockout phenotypes and used Cre-mediated deletion of Pofut2 and Adamts9 to dissect the tissue-specific role of O-fucosylated ADAMTS9 during gastrulation. 27297885 10 126 theme function 1910:1917 arg1 loss 1894:1897 loss 1894:1897 loss of ADAMTS9 function in the extra embryonic tissue 1894:1947 Combined, these results suggested that loss of ADAMTS9 function in the extra embryonic tissue is responsible for gastrulation defects in the Pofut2 knockout. 27297885 4 127 theme Adamts9 762:768 arg1 deletion 739:746 Cre-mediated deletion 726:746 Cre-mediated deletion of Pofut2 and Adamts9 726:768 To address this question, we compared the Pofut2 and Adamts9 knockout phenotypes and used Cre-mediated deletion of Pofut2 and Adamts9 to dissect the tissue-specific role of O-fucosylated ADAMTS9 during gastrulation. 27297885 2 128 theme type-1 351:356 arg1 motifs 358:363 ThromboSpondin type-1 motifs 336:363 ThromboSpondin type-1 motifs 336:363 Nearly half the POFUT2 targets belong to the A Disintegrin and Metalloprotease with ThromboSpondin type-1 motifs (ADAMTS) or ADAMTS-like family of proteins. 26556271 7 0 theme changing 1949:1956 arg1 environment 1970:1980 a constantly changing nutritional environment 1936:1980 a constantly changing nutritional environment 1936:1980 Our results reveal that sensing and metabolic triaging of glycans are complex processes that vary among species, underscoring the idea that these phenomena are likely to be hidden drivers of microbiota community dynamics and may dictate which microorganisms preferentially commit to various niches in a constantly changing nutritional environment. 26556271 9 1 theme refined 2277:2283 arg1 strategies 2285:2294 refined strategies 2277:2294 refined strategies 2277:2294 Complex carbohydrates are a major component of the intestinal habitat, and numerous species have evolved and refined strategies to compete for these coveted nutrients. 26556271 4 2 theme mucin 646:650 arg1 glycans 652:658 mucin glycans 646:658 mucin glycans 646:658 Experiments in which mucin glycans were presented simultaneously with other carbohydrates show that degradation of these host carbohydrates is consistently repressed in the presence of alternative substrates, even by B. thetaiotaomicron previously acclimated to growth in pure mucin glycans. 26556271 8 3 theme many 2033:2036 arg1 digestion 2079:2087 digestion 2079:2087 digestion 2079:2087 IMPORTANCE Human intestinal microorganisms impact many aspects of health and disease, including digestion and the propensity to develop disorders such as inflammation and colon cancer. 26556271 8 3 theme many 2033:2036 arg1 propensity 2097:2106 the propensity to develop disorders such as inflammation and colon cancer 2093:2165 the propensity to develop disorders such as inflammation and colon cancer 2093:2165 IMPORTANCE Human intestinal microorganisms impact many aspects of health and disease, including digestion and the propensity to develop disorders such as inflammation and colon cancer. 26556271 8 3 theme many 2033:2036 arg1 aspects 2038:2044 many aspects 2033:2044 many aspects 2033:2044 IMPORTANCE Human intestinal microorganisms impact many aspects of health and disease, including digestion and the propensity to develop disorders such as inflammation and colon cancer. 26556271 2 4 attach present 375:381 arg1 mixtures 386:393 mixtures 386:393 mixtures 386:393 Like microorganisms adapted to other complex nutrient environments, gut symbionts give different metabolic priorities to substrates present in mixtures. 26556271 2 4 attach present 375:381 arg2 substrates 364:373 substrates 364:373 substrates present in mixtures 364:393 Like microorganisms adapted to other complex nutrient environments, gut symbionts give different metabolic priorities to substrates present in mixtures. 26556271 6 5 theme gene 1280:1283 arg1 clusters 1285:1292 mucin glycan-responsive gene clusters 1256:1292 mucin glycan-responsive gene clusters 1256:1292 Repression of mucin glycan-responsive gene clusters in two other human gut bacteria, Bacteroides massiliensis and Bacteroides fragilis, exhibited variable and sometimes reciprocal responses compared to those of B. thetaiotaomicron, revealing that these symbionts vary in their preference for mucin glycans and that these differences occur at the level of controlling individual gene clusters. 26556271 2 6 theme nutrient 288:295 arg1 environments 297:308 other complex nutrient environments 274:308 other complex nutrient environments 274:308 Like microorganisms adapted to other complex nutrient environments, gut symbionts give different metabolic priorities to substrates present in mixtures. 26556271 6 7 theme mucin 1256:1260 arg1 clusters 1285:1292 mucin glycan-responsive gene clusters 1256:1292 mucin glycan-responsive gene clusters 1256:1292 Repression of mucin glycan-responsive gene clusters in two other human gut bacteria, Bacteroides massiliensis and Bacteroides fragilis, exhibited variable and sometimes reciprocal responses compared to those of B. thetaiotaomicron, revealing that these symbionts vary in their preference for mucin glycans and that these differences occur at the level of controlling individual gene clusters. 26556271 2 8 theme different 330:338 arg1 priorities 350:359 different metabolic priorities 330:359 different metabolic priorities 330:359 Like microorganisms adapted to other complex nutrient environments, gut symbionts give different metabolic priorities to substrates present in mixtures. 26556271 5 9 theme carbohydrate 973:984 arg1 cues 986:989 systematically varied carbohydrate cues 951:989 systematically varied carbohydrate cues 951:989 Experiments with media containing systematically varied carbohydrate cues and genetic mutants reveal that transcriptional repression of genes involved in mucin glycan metabolism is imposed by simple sugars and, in one example that was tested, is mediated through a small intergenic region in a transcript-autonomous fashion. 26556271 4 10 theme other 695:699 arg1 carbohydrates 701:713 other carbohydrates 695:713 other carbohydrates 695:713 Experiments in which mucin glycans were presented simultaneously with other carbohydrates show that degradation of these host carbohydrates is consistently repressed in the presence of alternative substrates, even by B. thetaiotaomicron previously acclimated to growth in pure mucin glycans. 26556271 5 11 theme genes 1053:1057 arg1 repression 1039:1048 transcriptional repression 1023:1048 transcriptional repression of genes involved in mucin glycan metabolism 1023:1093 Experiments with media containing systematically varied carbohydrate cues and genetic mutants reveal that transcriptional repression of genes involved in mucin glycan metabolism is imposed by simple sugars and, in one example that was tested, is mediated through a small intergenic region in a transcript-autonomous fashion. 26556271 6 12 theme B. 1453:1454 arg1 thetaiotaomicron 1456:1471 B. thetaiotaomicron 1453:1471 B. thetaiotaomicron 1453:1471 Repression of mucin glycan-responsive gene clusters in two other human gut bacteria, Bacteroides massiliensis and Bacteroides fragilis, exhibited variable and sometimes reciprocal responses compared to those of B. thetaiotaomicron, revealing that these symbionts vary in their preference for mucin glycans and that these differences occur at the level of controlling individual gene clusters. 26556271 3 13 theme secreted 609:616 arg1 mucin 618:622 secreted mucin 609:622 secreted mucin 609:622 We investigated the responses of Bacteroides thetaiotaomicron, a common human intestinal bacterium that metabolizes more than a dozen different polysaccharides, including the O-linked glycans that are abundant in secreted mucin. 26556271 10 14 theme prioritization 2500:2513 arg1 strategies 2515:2524 these prioritization strategies 2494:2524 these prioritization strategies 2494:2524 Our findings reveal that individual bacteria exhibit different preferences for carbohydrates emanating from host diet and mucosal secretions and that some of these prioritization strategies are opposite to one another. 26556271 11 15 theme complex 2699:2705 arg1 ecosystem 2711:2719 the complex gut ecosystem 2695:2719 the complex gut ecosystem 2695:2719 Thus, we reveal new aspects of how individual bacteria, some with otherwise similar metabolic potential, partition to "preferred niches" in the complex gut ecosystem, which has important and immediate implications for understanding and predicting the behavioral dynamics of this community. 26556271 5 16 dep imposed 1098:1104 arg1 mediated 1163:1170 mediated 1163:1170 is mediated through a small intergenic region in a transcript-autonomous fashion 1160:1239 Experiments with media containing systematically varied carbohydrate cues and genetic mutants reveal that transcriptional repression of genes involved in mucin glycan metabolism is imposed by simple sugars and, in one example that was tested, is mediated through a small intergenic region in a transcript-autonomous fashion. 26556271 6 17 theme gut 1313:1315 arg1 fragilis 1368:1375 Bacteroides fragilis 1356:1375 Bacteroides fragilis 1356:1375 Repression of mucin glycan-responsive gene clusters in two other human gut bacteria, Bacteroides massiliensis and Bacteroides fragilis, exhibited variable and sometimes reciprocal responses compared to those of B. thetaiotaomicron, revealing that these symbionts vary in their preference for mucin glycans and that these differences occur at the level of controlling individual gene clusters. 26556271 6 17 theme gut 1313:1315 arg1 bacteria 1317:1324 two other human gut bacteria 1297:1324 two other human gut bacteria 1297:1324 Repression of mucin glycan-responsive gene clusters in two other human gut bacteria, Bacteroides massiliensis and Bacteroides fragilis, exhibited variable and sometimes reciprocal responses compared to those of B. thetaiotaomicron, revealing that these symbionts vary in their preference for mucin glycans and that these differences occur at the level of controlling individual gene clusters. 26556271 6 17 theme gut 1313:1315 arg1 massiliensis 1339:1350 Bacteroides massiliensis 1327:1350 Bacteroides massiliensis 1327:1350 Repression of mucin glycan-responsive gene clusters in two other human gut bacteria, Bacteroides massiliensis and Bacteroides fragilis, exhibited variable and sometimes reciprocal responses compared to those of B. thetaiotaomicron, revealing that these symbionts vary in their preference for mucin glycans and that these differences occur at the level of controlling individual gene clusters. 26556271 11 18 theme individual 2590:2599 arg1 bacteria 2601:2608 individual bacteria 2590:2608 individual bacteria 2590:2608 Thus, we reveal new aspects of how individual bacteria, some with otherwise similar metabolic potential, partition to "preferred niches" in the complex gut ecosystem, which has important and immediate implications for understanding and predicting the behavioral dynamics of this community. 26556271 11 18 theme individual 2590:2599 arg1 some 2611:2614 some 2611:2614 some 2611:2614 Thus, we reveal new aspects of how individual bacteria, some with otherwise similar metabolic potential, partition to "preferred niches" in the complex gut ecosystem, which has important and immediate implications for understanding and predicting the behavioral dynamics of this community. 26556271 6 19 theme reciprocal 1411:1420 arg1 responses 1422:1430 variable and sometimes reciprocal responses 1388:1430 variable and sometimes reciprocal responses 1388:1430 Repression of mucin glycan-responsive gene clusters in two other human gut bacteria, Bacteroides massiliensis and Bacteroides fragilis, exhibited variable and sometimes reciprocal responses compared to those of B. thetaiotaomicron, revealing that these symbionts vary in their preference for mucin glycans and that these differences occur at the level of controlling individual gene clusters. 26556271 2 20 theme other 274:278 arg1 environments 297:308 other complex nutrient environments 274:308 other complex nutrient environments 274:308 Like microorganisms adapted to other complex nutrient environments, gut symbionts give different metabolic priorities to substrates present in mixtures. 26556271 4 21 from growth 887:892 arg1 glycans 908:914 pure mucin glycans 897:914 pure mucin glycans 897:914 Experiments in which mucin glycans were presented simultaneously with other carbohydrates show that degradation of these host carbohydrates is consistently repressed in the presence of alternative substrates, even by B. thetaiotaomicron previously acclimated to growth in pure mucin glycans. 26556271 6 22 theme other 1301:1305 arg1 fragilis 1368:1375 Bacteroides fragilis 1356:1375 Bacteroides fragilis 1356:1375 Repression of mucin glycan-responsive gene clusters in two other human gut bacteria, Bacteroides massiliensis and Bacteroides fragilis, exhibited variable and sometimes reciprocal responses compared to those of B. thetaiotaomicron, revealing that these symbionts vary in their preference for mucin glycans and that these differences occur at the level of controlling individual gene clusters. 26556271 6 22 theme other 1301:1305 arg1 bacteria 1317:1324 two other human gut bacteria 1297:1324 two other human gut bacteria 1297:1324 Repression of mucin glycan-responsive gene clusters in two other human gut bacteria, Bacteroides massiliensis and Bacteroides fragilis, exhibited variable and sometimes reciprocal responses compared to those of B. thetaiotaomicron, revealing that these symbionts vary in their preference for mucin glycans and that these differences occur at the level of controlling individual gene clusters. 26556271 6 22 theme other 1301:1305 arg1 massiliensis 1339:1350 Bacteroides massiliensis 1327:1350 Bacteroides massiliensis 1327:1350 Repression of mucin glycan-responsive gene clusters in two other human gut bacteria, Bacteroides massiliensis and Bacteroides fragilis, exhibited variable and sometimes reciprocal responses compared to those of B. thetaiotaomicron, revealing that these symbionts vary in their preference for mucin glycans and that these differences occur at the level of controlling individual gene clusters. 26556271 10 23 theme individual 2361:2370 arg1 bacteria 2372:2379 individual bacteria 2361:2379 individual bacteria 2361:2379 Our findings reveal that individual bacteria exhibit different preferences for carbohydrates emanating from host diet and mucosal secretions and that some of these prioritization strategies are opposite to one another. 26556271 4 24 theme carbohydrates 751:763 arg1 degradation 725:735 degradation 725:735 degradation of these host carbohydrates 725:763 Experiments in which mucin glycans were presented simultaneously with other carbohydrates show that degradation of these host carbohydrates is consistently repressed in the presence of alternative substrates, even by B. thetaiotaomicron previously acclimated to growth in pure mucin glycans. 26556271 7 25 theme community 1837:1845 arg1 dynamics 1847:1854 microbiota community dynamics 1826:1854 microbiota community dynamics 1826:1854 Our results reveal that sensing and metabolic triaging of glycans are complex processes that vary among species, underscoring the idea that these phenomena are likely to be hidden drivers of microbiota community dynamics and may dictate which microorganisms preferentially commit to various niches in a constantly changing nutritional environment. 26556271 7 26 theme complex 1705:1711 arg1 processes 1713:1721 complex processes 1705:1721 complex processes that vary among species, underscoring the idea that these phenomena are likely to be hidden drivers of microbiota community dynamics and may dictate which microorganisms preferentially commit to various niches in a constantly changing nutritional environment 1705:1980 Our results reveal that sensing and metabolic triaging of glycans are complex processes that vary among species, underscoring the idea that these phenomena are likely to be hidden drivers of microbiota community dynamics and may dictate which microorganisms preferentially commit to various niches in a constantly changing nutritional environment. 26556271 7 26 theme complex 1705:1711 arg1 triaging 1681:1688 sensing and metabolic triaging 1659:1688 sensing and metabolic triaging of glycans 1659:1699 Our results reveal that sensing and metabolic triaging of glycans are complex processes that vary among species, underscoring the idea that these phenomena are likely to be hidden drivers of microbiota community dynamics and may dictate which microorganisms preferentially commit to various niches in a constantly changing nutritional environment. 26556271 7 27 dep likely 1795:1800 arg1 dictate 1864:1870 dictate 1864:1870 may dictate which microorganisms preferentially commit to various niches in a constantly changing nutritional environment 1860:1980 Our results reveal that sensing and metabolic triaging of glycans are complex processes that vary among species, underscoring the idea that these phenomena are likely to be hidden drivers of microbiota community dynamics and may dictate which microorganisms preferentially commit to various niches in a constantly changing nutritional environment. 26556271 7 27 dep likely 1795:1800 arg1 phenomena 1781:1789 these phenomena 1775:1789 these phenomena 1775:1789 Our results reveal that sensing and metabolic triaging of glycans are complex processes that vary among species, underscoring the idea that these phenomena are likely to be hidden drivers of microbiota community dynamics and may dictate which microorganisms preferentially commit to various niches in a constantly changing nutritional environment. 26556271 7 27 dep likely 1795:1800 arg1 drivers 1815:1821 hidden drivers 1808:1821 hidden drivers of microbiota community dynamics 1808:1854 Our results reveal that sensing and metabolic triaging of glycans are complex processes that vary among species, underscoring the idea that these phenomena are likely to be hidden drivers of microbiota community dynamics and may dictate which microorganisms preferentially commit to various niches in a constantly changing nutritional environment. 26556271 0 28 theme Mucosal 73:79 arg1 Glycans 81:87 Host Mucosal Glycans 68:87 Host Mucosal Glycans 68:87 Symbiotic Human Gut Bacteria with Variable Metabolic Priorities for Host Mucosal Glycans. 26556271 5 29 theme transcript-autonomous 1211:1231 arg1 fashion 1233:1239 a transcript-autonomous fashion 1209:1239 a transcript-autonomous fashion 1209:1239 Experiments with media containing systematically varied carbohydrate cues and genetic mutants reveal that transcriptional repression of genes involved in mucin glycan metabolism is imposed by simple sugars and, in one example that was tested, is mediated through a small intergenic region in a transcript-autonomous fashion. 26556271 1 30 theme multiple 160:167 arg1 polysaccharides 169:183 multiple polysaccharides 160:183 multiple polysaccharides 160:183 UNLABELLED Many symbiotic gut bacteria possess the ability to degrade multiple polysaccharides, thereby providing nutritional advantages to their hosts. 26556271 7 31 theme glycans 1693:1699 arg1 processes 1713:1721 complex processes 1705:1721 complex processes that vary among species, underscoring the idea that these phenomena are likely to be hidden drivers of microbiota community dynamics and may dictate which microorganisms preferentially commit to various niches in a constantly changing nutritional environment 1705:1980 Our results reveal that sensing and metabolic triaging of glycans are complex processes that vary among species, underscoring the idea that these phenomena are likely to be hidden drivers of microbiota community dynamics and may dictate which microorganisms preferentially commit to various niches in a constantly changing nutritional environment. 26556271 7 31 theme glycans 1693:1699 arg1 triaging 1681:1688 sensing and metabolic triaging 1659:1688 sensing and metabolic triaging of glycans 1659:1699 Our results reveal that sensing and metabolic triaging of glycans are complex processes that vary among species, underscoring the idea that these phenomena are likely to be hidden drivers of microbiota community dynamics and may dictate which microorganisms preferentially commit to various niches in a constantly changing nutritional environment. 26556271 11 32 theme similar 2631:2637 arg1 potential 2649:2657 otherwise similar metabolic potential 2621:2657 otherwise similar metabolic potential 2621:2657 Thus, we reveal new aspects of how individual bacteria, some with otherwise similar metabolic potential, partition to "preferred niches" in the complex gut ecosystem, which has important and immediate implications for understanding and predicting the behavioral dynamics of this community. 26556271 2 33 from present 375:381 arg1 mixtures 386:393 mixtures 386:393 mixtures 386:393 Like microorganisms adapted to other complex nutrient environments, gut symbionts give different metabolic priorities to substrates present in mixtures. 26556271 3 34 from abundant 597:604 arg1 mucin 618:622 secreted mucin 609:622 secreted mucin 609:622 We investigated the responses of Bacteroides thetaiotaomicron, a common human intestinal bacterium that metabolizes more than a dozen different polysaccharides, including the O-linked glycans that are abundant in secreted mucin. 26556271 5 35 theme glycan 1077:1082 arg1 metabolism 1084:1093 mucin glycan metabolism 1071:1093 mucin glycan metabolism 1071:1093 Experiments with media containing systematically varied carbohydrate cues and genetic mutants reveal that transcriptional repression of genes involved in mucin glycan metabolism is imposed by simple sugars and, in one example that was tested, is mediated through a small intergenic region in a transcript-autonomous fashion. 26556271 7 36 theme hidden 1808:1813 arg1 phenomena 1781:1789 these phenomena 1775:1789 these phenomena 1775:1789 Our results reveal that sensing and metabolic triaging of glycans are complex processes that vary among species, underscoring the idea that these phenomena are likely to be hidden drivers of microbiota community dynamics and may dictate which microorganisms preferentially commit to various niches in a constantly changing nutritional environment. 26556271 7 36 theme hidden 1808:1813 arg1 drivers 1815:1821 hidden drivers 1808:1821 hidden drivers of microbiota community dynamics 1808:1854 Our results reveal that sensing and metabolic triaging of glycans are complex processes that vary among species, underscoring the idea that these phenomena are likely to be hidden drivers of microbiota community dynamics and may dictate which microorganisms preferentially commit to various niches in a constantly changing nutritional environment. 26556271 5 37 contain containing 940:949 arg2 cues 986:989 systematically varied carbohydrate cues 951:989 systematically varied carbohydrate cues 951:989 Experiments with media containing systematically varied carbohydrate cues and genetic mutants reveal that transcriptional repression of genes involved in mucin glycan metabolism is imposed by simple sugars and, in one example that was tested, is mediated through a small intergenic region in a transcript-autonomous fashion. 26556271 5 37 contain containing 940:949 arg1 media 934:938 media 934:938 media containing systematically varied carbohydrate cues 934:989 Experiments with media containing systematically varied carbohydrate cues and genetic mutants reveal that transcriptional repression of genes involved in mucin glycan metabolism is imposed by simple sugars and, in one example that was tested, is mediated through a small intergenic region in a transcript-autonomous fashion. 26556271 3 38 theme intestinal 474:483 arg1 thetaiotaomicron 441:456 Bacteroides thetaiotaomicron 429:456 Bacteroides thetaiotaomicron 429:456 We investigated the responses of Bacteroides thetaiotaomicron, a common human intestinal bacterium that metabolizes more than a dozen different polysaccharides, including the O-linked glycans that are abundant in secreted mucin. 26556271 3 38 theme intestinal 474:483 arg1 bacterium 485:493 a common human intestinal bacterium 459:493 a common human intestinal bacterium that metabolizes more than a dozen different polysaccharides, including the O-linked glycans that are abundant in secreted mucin 459:622 We investigated the responses of Bacteroides thetaiotaomicron, a common human intestinal bacterium that metabolizes more than a dozen different polysaccharides, including the O-linked glycans that are abundant in secreted mucin. 26556271 5 39 theme intergenic 1188:1197 arg1 region 1199:1204 a small intergenic region 1180:1204 a small intergenic region in a transcript-autonomous fashion 1180:1239 Experiments with media containing systematically varied carbohydrate cues and genetic mutants reveal that transcriptional repression of genes involved in mucin glycan metabolism is imposed by simple sugars and, in one example that was tested, is mediated through a small intergenic region in a transcript-autonomous fashion. 26556271 8 40 theme IMPORTANCE 1983:1992 arg1 microorganisms 2011:2024 IMPORTANCE Human intestinal microorganisms 1983:2024 IMPORTANCE Human intestinal microorganisms 1983:2024 IMPORTANCE Human intestinal microorganisms impact many aspects of health and disease, including digestion and the propensity to develop disorders such as inflammation and colon cancer. 26556271 11 41 contain has 2728:2730 arg1 ecosystem 2711:2719 the complex gut ecosystem 2695:2719 the complex gut ecosystem 2695:2719 Thus, we reveal new aspects of how individual bacteria, some with otherwise similar metabolic potential, partition to "preferred niches" in the complex gut ecosystem, which has important and immediate implications for understanding and predicting the behavioral dynamics of this community. 26556271 11 41 contain has 2728:2730 arg2 implications 2756:2767 important and immediate implications 2732:2767 important and immediate implications for understanding and predicting the behavioral dynamics of this community 2732:2842 Thus, we reveal new aspects of how individual bacteria, some with otherwise similar metabolic potential, partition to "preferred niches" in the complex gut ecosystem, which has important and immediate implications for understanding and predicting the behavioral dynamics of this community. 26556271 4 42 theme alternative 810:820 arg1 substrates 822:831 alternative substrates 810:831 alternative substrates 810:831 Experiments in which mucin glycans were presented simultaneously with other carbohydrates show that degradation of these host carbohydrates is consistently repressed in the presence of alternative substrates, even by B. thetaiotaomicron previously acclimated to growth in pure mucin glycans. 26556271 3 43 theme common 461:466 arg1 thetaiotaomicron 441:456 Bacteroides thetaiotaomicron 429:456 Bacteroides thetaiotaomicron 429:456 We investigated the responses of Bacteroides thetaiotaomicron, a common human intestinal bacterium that metabolizes more than a dozen different polysaccharides, including the O-linked glycans that are abundant in secreted mucin. 26556271 3 43 theme common 461:466 arg1 bacterium 485:493 a common human intestinal bacterium 459:493 a common human intestinal bacterium that metabolizes more than a dozen different polysaccharides, including the O-linked glycans that are abundant in secreted mucin 459:622 We investigated the responses of Bacteroides thetaiotaomicron, a common human intestinal bacterium that metabolizes more than a dozen different polysaccharides, including the O-linked glycans that are abundant in secreted mucin. 26556271 0 44 theme Symbiotic 0:8 arg1 Bacteria 20:27 Symbiotic Human Gut Bacteria 0:27 Symbiotic Human Gut Bacteria with Variable Metabolic Priorities for Host Mucosal Glycans. 0:88 Symbiotic Human Gut Bacteria with Variable Metabolic Priorities for Host Mucosal Glycans. 26556271 8 45 theme intestinal 2000:2009 arg1 microorganisms 2011:2024 IMPORTANCE Human intestinal microorganisms 1983:2024 IMPORTANCE Human intestinal microorganisms 1983:2024 IMPORTANCE Human intestinal microorganisms impact many aspects of health and disease, including digestion and the propensity to develop disorders such as inflammation and colon cancer. 26556271 1 46 theme UNLABELLED 90:99 arg1 bacteria 120:127 UNLABELLED Many symbiotic gut bacteria 90:127 UNLABELLED Many symbiotic gut bacteria 90:127 UNLABELLED Many symbiotic gut bacteria possess the ability to degrade multiple polysaccharides, thereby providing nutritional advantages to their hosts. 26556271 11 47 theme new 2571:2573 arg1 aspects 2575:2581 new aspects 2571:2581 new aspects of how individual bacteria, some with otherwise similar metabolic potential, partition to "preferred niches" in the complex gut ecosystem, which has important and immediate implications for understanding and predicting the behavioral dynamics of this community 2571:2842 Thus, we reveal new aspects of how individual bacteria, some with otherwise similar metabolic potential, partition to "preferred niches" in the complex gut ecosystem, which has important and immediate implications for understanding and predicting the behavioral dynamics of this community. 26556271 0 48 theme Gut 16:18 arg1 Bacteria 20:27 Symbiotic Human Gut Bacteria 0:27 Symbiotic Human Gut Bacteria with Variable Metabolic Priorities for Host Mucosal Glycans. 0:88 Symbiotic Human Gut Bacteria with Variable Metabolic Priorities for Host Mucosal Glycans. 26556271 7 49 theme sensing 1659:1665 arg1 processes 1713:1721 complex processes 1705:1721 complex processes that vary among species, underscoring the idea that these phenomena are likely to be hidden drivers of microbiota community dynamics and may dictate which microorganisms preferentially commit to various niches in a constantly changing nutritional environment 1705:1980 Our results reveal that sensing and metabolic triaging of glycans are complex processes that vary among species, underscoring the idea that these phenomena are likely to be hidden drivers of microbiota community dynamics and may dictate which microorganisms preferentially commit to various niches in a constantly changing nutritional environment. 26556271 7 49 theme sensing 1659:1665 arg1 triaging 1681:1688 sensing and metabolic triaging 1659:1688 sensing and metabolic triaging of glycans 1659:1699 Our results reveal that sensing and metabolic triaging of glycans are complex processes that vary among species, underscoring the idea that these phenomena are likely to be hidden drivers of microbiota community dynamics and may dictate which microorganisms preferentially commit to various niches in a constantly changing nutritional environment. 26556271 1 50 theme symbiotic 106:114 arg1 bacteria 120:127 UNLABELLED Many symbiotic gut bacteria 90:127 UNLABELLED Many symbiotic gut bacteria 90:127 UNLABELLED Many symbiotic gut bacteria possess the ability to degrade multiple polysaccharides, thereby providing nutritional advantages to their hosts. 26556271 9 51 theme habitat 2230:2236 arg1 component 2202:2210 a major component 2194:2210 a major component of the intestinal habitat 2194:2236 Complex carbohydrates are a major component of the intestinal habitat, and numerous species have evolved and refined strategies to compete for these coveted nutrients. 26556271 9 51 theme habitat 2230:2236 arg1 carbohydrates 2176:2188 Complex carbohydrates 2168:2188 Complex carbohydrates 2168:2188 Complex carbohydrates are a major component of the intestinal habitat, and numerous species have evolved and refined strategies to compete for these coveted nutrients. 26556271 4 52 theme pure 897:900 arg1 glycans 908:914 pure mucin glycans 897:914 pure mucin glycans 897:914 Experiments in which mucin glycans were presented simultaneously with other carbohydrates show that degradation of these host carbohydrates is consistently repressed in the presence of alternative substrates, even by B. thetaiotaomicron previously acclimated to growth in pure mucin glycans. 26556271 6 53 theme mucin 1534:1538 arg1 glycans 1540:1546 mucin glycans 1534:1546 mucin glycans 1534:1546 Repression of mucin glycan-responsive gene clusters in two other human gut bacteria, Bacteroides massiliensis and Bacteroides fragilis, exhibited variable and sometimes reciprocal responses compared to those of B. thetaiotaomicron, revealing that these symbionts vary in their preference for mucin glycans and that these differences occur at the level of controlling individual gene clusters. 26556271 3 54 theme Bacteroides 429:439 arg1 thetaiotaomicron 441:456 Bacteroides thetaiotaomicron 429:456 Bacteroides thetaiotaomicron 429:456 We investigated the responses of Bacteroides thetaiotaomicron, a common human intestinal bacterium that metabolizes more than a dozen different polysaccharides, including the O-linked glycans that are abundant in secreted mucin. 26556271 3 54 theme Bacteroides 429:439 arg1 bacterium 485:493 a common human intestinal bacterium 459:493 a common human intestinal bacterium that metabolizes more than a dozen different polysaccharides, including the O-linked glycans that are abundant in secreted mucin 459:622 We investigated the responses of Bacteroides thetaiotaomicron, a common human intestinal bacterium that metabolizes more than a dozen different polysaccharides, including the O-linked glycans that are abundant in secreted mucin. 26556271 3 55 theme different 530:538 arg1 glycans 580:586 the O-linked glycans 567:586 the O-linked glycans that are abundant in secreted mucin 567:622 We investigated the responses of Bacteroides thetaiotaomicron, a common human intestinal bacterium that metabolizes more than a dozen different polysaccharides, including the O-linked glycans that are abundant in secreted mucin. 26556271 3 55 theme different 530:538 arg1 polysaccharides 540:554 a dozen different polysaccharides 522:554 a dozen different polysaccharides 522:554 We investigated the responses of Bacteroides thetaiotaomicron, a common human intestinal bacterium that metabolizes more than a dozen different polysaccharides, including the O-linked glycans that are abundant in secreted mucin. 26556271 0 56 theme Metabolic 43:51 arg1 Priorities 53:62 Variable Metabolic Priorities 34:62 Variable Metabolic Priorities for Host Mucosal Glycans 34:87 Symbiotic Human Gut Bacteria with Variable Metabolic Priorities for Host Mucosal Glycans. 26556271 6 57 theme individual 1609:1618 arg1 clusters 1625:1632 individual gene clusters 1609:1632 individual gene clusters 1609:1632 Repression of mucin glycan-responsive gene clusters in two other human gut bacteria, Bacteroides massiliensis and Bacteroides fragilis, exhibited variable and sometimes reciprocal responses compared to those of B. thetaiotaomicron, revealing that these symbionts vary in their preference for mucin glycans and that these differences occur at the level of controlling individual gene clusters. 26556271 7 58 theme nutritional 1958:1968 arg1 environment 1970:1980 a constantly changing nutritional environment 1936:1980 a constantly changing nutritional environment 1936:1980 Our results reveal that sensing and metabolic triaging of glycans are complex processes that vary among species, underscoring the idea that these phenomena are likely to be hidden drivers of microbiota community dynamics and may dictate which microorganisms preferentially commit to various niches in a constantly changing nutritional environment. 26556271 11 59 theme immediate 2746:2754 arg1 implications 2756:2767 important and immediate implications 2732:2767 important and immediate implications for understanding and predicting the behavioral dynamics of this community 2732:2842 Thus, we reveal new aspects of how individual bacteria, some with otherwise similar metabolic potential, partition to "preferred niches" in the complex gut ecosystem, which has important and immediate implications for understanding and predicting the behavioral dynamics of this community. 26556271 7 60 from niches 1926:1931 arg1 environment 1970:1980 a constantly changing nutritional environment 1936:1980 a constantly changing nutritional environment 1936:1980 Our results reveal that sensing and metabolic triaging of glycans are complex processes that vary among species, underscoring the idea that these phenomena are likely to be hidden drivers of microbiota community dynamics and may dictate which microorganisms preferentially commit to various niches in a constantly changing nutritional environment. 26556271 11 61 theme important 2732:2740 arg1 implications 2756:2767 important and immediate implications 2732:2767 important and immediate implications for understanding and predicting the behavioral dynamics of this community 2732:2842 Thus, we reveal new aspects of how individual bacteria, some with otherwise similar metabolic potential, partition to "preferred niches" in the complex gut ecosystem, which has important and immediate implications for understanding and predicting the behavioral dynamics of this community. 26556271 1 62 contain possess 129:135 arg1 bacteria 120:127 UNLABELLED Many symbiotic gut bacteria 90:127 UNLABELLED Many symbiotic gut bacteria 90:127 UNLABELLED Many symbiotic gut bacteria possess the ability to degrade multiple polysaccharides, thereby providing nutritional advantages to their hosts. 26556271 1 62 contain possess 129:135 arg2 ability 141:147 the ability to degrade multiple polysaccharides 137:183 the ability to degrade multiple polysaccharides 137:183 UNLABELLED Many symbiotic gut bacteria possess the ability to degrade multiple polysaccharides, thereby providing nutritional advantages to their hosts. 26556271 10 63 dep one 2542:2544 arg1 another 2546:2552 another 2546:2552 another 2546:2552 Our findings reveal that individual bacteria exhibit different preferences for carbohydrates emanating from host diet and mucosal secretions and that some of these prioritization strategies are opposite to one another. 26556271 10 64 theme mucosal 2458:2464 arg1 secretions 2466:2475 mucosal secretions 2458:2475 mucosal secretions 2458:2475 Our findings reveal that individual bacteria exhibit different preferences for carbohydrates emanating from host diet and mucosal secretions and that some of these prioritization strategies are opposite to one another. 26556271 6 65 theme variable 1388:1395 arg1 responses 1422:1430 variable and sometimes reciprocal responses 1388:1430 variable and sometimes reciprocal responses 1388:1430 Repression of mucin glycan-responsive gene clusters in two other human gut bacteria, Bacteroides massiliensis and Bacteroides fragilis, exhibited variable and sometimes reciprocal responses compared to those of B. thetaiotaomicron, revealing that these symbionts vary in their preference for mucin glycans and that these differences occur at the level of controlling individual gene clusters. 26556271 2 66 theme gut 311:313 arg1 symbionts 315:323 gut symbionts 311:323 gut symbionts 311:323 Like microorganisms adapted to other complex nutrient environments, gut symbionts give different metabolic priorities to substrates present in mixtures. 26556271 7 67 theme various 1918:1924 arg1 niches 1926:1931 various niches 1918:1931 various niches in a constantly changing nutritional environment 1918:1980 Our results reveal that sensing and metabolic triaging of glycans are complex processes that vary among species, underscoring the idea that these phenomena are likely to be hidden drivers of microbiota community dynamics and may dictate which microorganisms preferentially commit to various niches in a constantly changing nutritional environment. 26556271 6 68 theme clusters 1285:1292 arg1 Repression 1242:1251 Repression 1242:1251 Repression of mucin glycan-responsive gene clusters in two other human gut bacteria, Bacteroides massiliensis and Bacteroides fragilis, 1242:1376 Repression of mucin glycan-responsive gene clusters in two other human gut bacteria, Bacteroides massiliensis and Bacteroides fragilis, exhibited variable and sometimes reciprocal responses compared to those of B. thetaiotaomicron, revealing that these symbionts vary in their preference for mucin glycans and that these differences occur at the level of controlling individual gene clusters. 26556271 2 69 theme present 375:381 arg1 substrates 364:373 substrates 364:373 substrates present in mixtures 364:393 Like microorganisms adapted to other complex nutrient environments, gut symbionts give different metabolic priorities to substrates present in mixtures. 26556271 8 70 theme health 2049:2054 arg1 digestion 2079:2087 digestion 2079:2087 digestion 2079:2087 IMPORTANCE Human intestinal microorganisms impact many aspects of health and disease, including digestion and the propensity to develop disorders such as inflammation and colon cancer. 26556271 8 70 theme health 2049:2054 arg1 propensity 2097:2106 the propensity to develop disorders such as inflammation and colon cancer 2093:2165 the propensity to develop disorders such as inflammation and colon cancer 2093:2165 IMPORTANCE Human intestinal microorganisms impact many aspects of health and disease, including digestion and the propensity to develop disorders such as inflammation and colon cancer. 26556271 8 70 theme health 2049:2054 arg1 aspects 2038:2044 many aspects 2033:2044 many aspects 2033:2044 IMPORTANCE Human intestinal microorganisms impact many aspects of health and disease, including digestion and the propensity to develop disorders such as inflammation and colon cancer. 26556271 2 71 from mixtures 386:393 arg1 present 375:381 present 375:381 present 375:381 Like microorganisms adapted to other complex nutrient environments, gut symbionts give different metabolic priorities to substrates present in mixtures. 26556271 6 72 theme glycan-responsive 1262:1278 arg1 clusters 1285:1292 mucin glycan-responsive gene clusters 1256:1292 mucin glycan-responsive gene clusters 1256:1292 Repression of mucin glycan-responsive gene clusters in two other human gut bacteria, Bacteroides massiliensis and Bacteroides fragilis, exhibited variable and sometimes reciprocal responses compared to those of B. thetaiotaomicron, revealing that these symbionts vary in their preference for mucin glycans and that these differences occur at the level of controlling individual gene clusters. 26556271 9 73 theme coveted 2317:2323 arg1 nutrients 2325:2333 these coveted nutrients 2311:2333 these coveted nutrients 2311:2333 Complex carbohydrates are a major component of the intestinal habitat, and numerous species have evolved and refined strategies to compete for these coveted nutrients. 26556271 8 74 theme disease 2060:2066 arg1 digestion 2079:2087 digestion 2079:2087 digestion 2079:2087 IMPORTANCE Human intestinal microorganisms impact many aspects of health and disease, including digestion and the propensity to develop disorders such as inflammation and colon cancer. 26556271 8 74 theme disease 2060:2066 arg1 propensity 2097:2106 the propensity to develop disorders such as inflammation and colon cancer 2093:2165 the propensity to develop disorders such as inflammation and colon cancer 2093:2165 IMPORTANCE Human intestinal microorganisms impact many aspects of health and disease, including digestion and the propensity to develop disorders such as inflammation and colon cancer. 26556271 8 74 theme disease 2060:2066 arg1 aspects 2038:2044 many aspects 2033:2044 many aspects 2033:2044 IMPORTANCE Human intestinal microorganisms impact many aspects of health and disease, including digestion and the propensity to develop disorders such as inflammation and colon cancer. 26556271 2 75 theme metabolic 340:348 arg1 priorities 350:359 different metabolic priorities 330:359 different metabolic priorities 330:359 Like microorganisms adapted to other complex nutrient environments, gut symbionts give different metabolic priorities to substrates present in mixtures. 26556271 5 76 theme varied 966:971 arg1 cues 986:989 systematically varied carbohydrate cues 951:989 systematically varied carbohydrate cues 951:989 Experiments with media containing systematically varied carbohydrate cues and genetic mutants reveal that transcriptional repression of genes involved in mucin glycan metabolism is imposed by simple sugars and, in one example that was tested, is mediated through a small intergenic region in a transcript-autonomous fashion. 26556271 1 77 theme nutritional 204:214 arg1 advantages 216:225 nutritional advantages 204:225 nutritional advantages 204:225 UNLABELLED Many symbiotic gut bacteria possess the ability to degrade multiple polysaccharides, thereby providing nutritional advantages to their hosts. 26556271 3 78 link O-linked 571:578 arg1 glycans 580:586 the O-linked glycans 567:586 the O-linked glycans that are abundant in secreted mucin 567:622 We investigated the responses of Bacteroides thetaiotaomicron, a common human intestinal bacterium that metabolizes more than a dozen different polysaccharides, including the O-linked glycans that are abundant in secreted mucin. 26556271 3 78 link O-linked 571:578 arg1 abundant 597:604 abundant 597:604 abundant 597:604 We investigated the responses of Bacteroides thetaiotaomicron, a common human intestinal bacterium that metabolizes more than a dozen different polysaccharides, including the O-linked glycans that are abundant in secreted mucin. 26556271 5 79 from region 1199:1204 arg1 fashion 1233:1239 a transcript-autonomous fashion 1209:1239 a transcript-autonomous fashion 1209:1239 Experiments with media containing systematically varied carbohydrate cues and genetic mutants reveal that transcriptional repression of genes involved in mucin glycan metabolism is imposed by simple sugars and, in one example that was tested, is mediated through a small intergenic region in a transcript-autonomous fashion. 26556271 1 80 theme gut 116:118 arg1 bacteria 120:127 UNLABELLED Many symbiotic gut bacteria 90:127 UNLABELLED Many symbiotic gut bacteria 90:127 UNLABELLED Many symbiotic gut bacteria possess the ability to degrade multiple polysaccharides, thereby providing nutritional advantages to their hosts. 26556271 2 81 theme complex 280:286 arg1 environments 297:308 other complex nutrient environments 274:308 other complex nutrient environments 274:308 Like microorganisms adapted to other complex nutrient environments, gut symbionts give different metabolic priorities to substrates present in mixtures. 26556271 5 82 theme transcriptional 1023:1037 arg1 repression 1039:1048 transcriptional repression 1023:1048 transcriptional repression of genes involved in mucin glycan metabolism 1023:1093 Experiments with media containing systematically varied carbohydrate cues and genetic mutants reveal that transcriptional repression of genes involved in mucin glycan metabolism is imposed by simple sugars and, in one example that was tested, is mediated through a small intergenic region in a transcript-autonomous fashion. 26556271 11 83 theme gut 2707:2709 arg1 ecosystem 2711:2719 the complex gut ecosystem 2695:2719 the complex gut ecosystem 2695:2719 Thus, we reveal new aspects of how individual bacteria, some with otherwise similar metabolic potential, partition to "preferred niches" in the complex gut ecosystem, which has important and immediate implications for understanding and predicting the behavioral dynamics of this community. 26556271 6 84 theme human 1307:1311 arg1 fragilis 1368:1375 Bacteroides fragilis 1356:1375 Bacteroides fragilis 1356:1375 Repression of mucin glycan-responsive gene clusters in two other human gut bacteria, Bacteroides massiliensis and Bacteroides fragilis, exhibited variable and sometimes reciprocal responses compared to those of B. thetaiotaomicron, revealing that these symbionts vary in their preference for mucin glycans and that these differences occur at the level of controlling individual gene clusters. 26556271 6 84 theme human 1307:1311 arg1 bacteria 1317:1324 two other human gut bacteria 1297:1324 two other human gut bacteria 1297:1324 Repression of mucin glycan-responsive gene clusters in two other human gut bacteria, Bacteroides massiliensis and Bacteroides fragilis, exhibited variable and sometimes reciprocal responses compared to those of B. thetaiotaomicron, revealing that these symbionts vary in their preference for mucin glycans and that these differences occur at the level of controlling individual gene clusters. 26556271 6 84 theme human 1307:1311 arg1 massiliensis 1339:1350 Bacteroides massiliensis 1327:1350 Bacteroides massiliensis 1327:1350 Repression of mucin glycan-responsive gene clusters in two other human gut bacteria, Bacteroides massiliensis and Bacteroides fragilis, exhibited variable and sometimes reciprocal responses compared to those of B. thetaiotaomicron, revealing that these symbionts vary in their preference for mucin glycans and that these differences occur at the level of controlling individual gene clusters. 26556271 3 85 from mucin 618:622 arg1 glycans 580:586 the O-linked glycans 567:586 the O-linked glycans that are abundant in secreted mucin 567:622 We investigated the responses of Bacteroides thetaiotaomicron, a common human intestinal bacterium that metabolizes more than a dozen different polysaccharides, including the O-linked glycans that are abundant in secreted mucin. 26556271 3 85 from mucin 618:622 arg1 abundant 597:604 abundant 597:604 abundant 597:604 We investigated the responses of Bacteroides thetaiotaomicron, a common human intestinal bacterium that metabolizes more than a dozen different polysaccharides, including the O-linked glycans that are abundant in secreted mucin. 26556271 0 86 theme Host 68:71 arg1 Glycans 81:87 Host Mucosal Glycans 68:87 Host Mucosal Glycans 68:87 Symbiotic Human Gut Bacteria with Variable Metabolic Priorities for Host Mucosal Glycans. 26556271 4 87 theme host 746:749 arg1 carbohydrates 751:763 these host carbohydrates 740:763 these host carbohydrates 740:763 Experiments in which mucin glycans were presented simultaneously with other carbohydrates show that degradation of these host carbohydrates is consistently repressed in the presence of alternative substrates, even by B. thetaiotaomicron previously acclimated to growth in pure mucin glycans. 26556271 5 88 theme genetic 995:1001 arg1 mutants 1003:1009 genetic mutants 995:1009 genetic mutants 995:1009 Experiments with media containing systematically varied carbohydrate cues and genetic mutants reveal that transcriptional repression of genes involved in mucin glycan metabolism is imposed by simple sugars and, in one example that was tested, is mediated through a small intergenic region in a transcript-autonomous fashion. 26556271 7 89 theme dynamics 1847:1854 arg1 phenomena 1781:1789 these phenomena 1775:1789 these phenomena 1775:1789 Our results reveal that sensing and metabolic triaging of glycans are complex processes that vary among species, underscoring the idea that these phenomena are likely to be hidden drivers of microbiota community dynamics and may dictate which microorganisms preferentially commit to various niches in a constantly changing nutritional environment. 26556271 7 89 theme dynamics 1847:1854 arg1 drivers 1815:1821 hidden drivers 1808:1821 hidden drivers of microbiota community dynamics 1808:1854 Our results reveal that sensing and metabolic triaging of glycans are complex processes that vary among species, underscoring the idea that these phenomena are likely to be hidden drivers of microbiota community dynamics and may dictate which microorganisms preferentially commit to various niches in a constantly changing nutritional environment. 26556271 11 90 theme metabolic 2639:2647 arg1 potential 2649:2657 otherwise similar metabolic potential 2621:2657 otherwise similar metabolic potential 2621:2657 Thus, we reveal new aspects of how individual bacteria, some with otherwise similar metabolic potential, partition to "preferred niches" in the complex gut ecosystem, which has important and immediate implications for understanding and predicting the behavioral dynamics of this community. 26556271 9 91 theme Complex 2168:2174 arg1 component 2202:2210 a major component 2194:2210 a major component of the intestinal habitat 2194:2236 Complex carbohydrates are a major component of the intestinal habitat, and numerous species have evolved and refined strategies to compete for these coveted nutrients. 26556271 9 91 theme Complex 2168:2174 arg1 carbohydrates 2176:2188 Complex carbohydrates 2168:2188 Complex carbohydrates 2168:2188 Complex carbohydrates are a major component of the intestinal habitat, and numerous species have evolved and refined strategies to compete for these coveted nutrients. 26556271 8 92 theme colon 2154:2158 arg1 cancer 2160:2165 colon cancer 2154:2165 colon cancer 2154:2165 IMPORTANCE Human intestinal microorganisms impact many aspects of health and disease, including digestion and the propensity to develop disorders such as inflammation and colon cancer. 26556271 5 93 theme mucin 1071:1075 arg1 metabolism 1084:1093 mucin glycan metabolism 1071:1093 mucin glycan metabolism 1071:1093 Experiments with media containing systematically varied carbohydrate cues and genetic mutants reveal that transcriptional repression of genes involved in mucin glycan metabolism is imposed by simple sugars and, in one example that was tested, is mediated through a small intergenic region in a transcript-autonomous fashion. 26556271 7 94 theme microbiota 1826:1835 arg1 dynamics 1847:1854 microbiota community dynamics 1826:1854 microbiota community dynamics 1826:1854 Our results reveal that sensing and metabolic triaging of glycans are complex processes that vary among species, underscoring the idea that these phenomena are likely to be hidden drivers of microbiota community dynamics and may dictate which microorganisms preferentially commit to various niches in a constantly changing nutritional environment. 26556271 7 95 theme metabolic 1671:1679 arg1 processes 1713:1721 complex processes 1705:1721 complex processes that vary among species, underscoring the idea that these phenomena are likely to be hidden drivers of microbiota community dynamics and may dictate which microorganisms preferentially commit to various niches in a constantly changing nutritional environment 1705:1980 Our results reveal that sensing and metabolic triaging of glycans are complex processes that vary among species, underscoring the idea that these phenomena are likely to be hidden drivers of microbiota community dynamics and may dictate which microorganisms preferentially commit to various niches in a constantly changing nutritional environment. 26556271 7 95 theme metabolic 1671:1679 arg1 triaging 1681:1688 sensing and metabolic triaging 1659:1688 sensing and metabolic triaging of glycans 1659:1699 Our results reveal that sensing and metabolic triaging of glycans are complex processes that vary among species, underscoring the idea that these phenomena are likely to be hidden drivers of microbiota community dynamics and may dictate which microorganisms preferentially commit to various niches in a constantly changing nutritional environment. 26556271 11 96 theme preferred 2674:2682 arg1 niches 2684:2689 "preferred niches 2673:2689 "preferred niches" in the complex gut ecosystem, which has important and immediate implications for understanding and predicting the behavioral dynamics of this community 2673:2842 Thus, we reveal new aspects of how individual bacteria, some with otherwise similar metabolic potential, partition to "preferred niches" in the complex gut ecosystem, which has important and immediate implications for understanding and predicting the behavioral dynamics of this community. 26556271 10 97 theme different 2389:2397 arg1 preferences 2399:2409 different preferences 2389:2409 different preferences for carbohydrates emanating from host diet and mucosal secretions 2389:2475 Our findings reveal that individual bacteria exhibit different preferences for carbohydrates emanating from host diet and mucosal secretions and that some of these prioritization strategies are opposite to one another. 26556271 5 98 theme small 1182:1186 arg1 region 1199:1204 a small intergenic region 1180:1204 a small intergenic region in a transcript-autonomous fashion 1180:1239 Experiments with media containing systematically varied carbohydrate cues and genetic mutants reveal that transcriptional repression of genes involved in mucin glycan metabolism is imposed by simple sugars and, in one example that was tested, is mediated through a small intergenic region in a transcript-autonomous fashion. 26556271 9 99 theme major 2196:2200 arg1 component 2202:2210 a major component 2194:2210 a major component of the intestinal habitat 2194:2236 Complex carbohydrates are a major component of the intestinal habitat, and numerous species have evolved and refined strategies to compete for these coveted nutrients. 26556271 9 99 theme major 2196:2200 arg1 carbohydrates 2176:2188 Complex carbohydrates 2168:2188 Complex carbohydrates 2168:2188 Complex carbohydrates are a major component of the intestinal habitat, and numerous species have evolved and refined strategies to compete for these coveted nutrients. 26556271 4 100 theme B. 842:843 arg1 thetaiotaomicron 845:860 B. thetaiotaomicron 842:860 B. thetaiotaomicron previously acclimated to growth in pure mucin glycans 842:914 Experiments in which mucin glycans were presented simultaneously with other carbohydrates show that degradation of these host carbohydrates is consistently repressed in the presence of alternative substrates, even by B. thetaiotaomicron previously acclimated to growth in pure mucin glycans. 26556271 0 101 theme Human 10:14 arg1 Bacteria 20:27 Symbiotic Human Gut Bacteria 0:27 Symbiotic Human Gut Bacteria with Variable Metabolic Priorities for Host Mucosal Glycans. 0:88 Symbiotic Human Gut Bacteria with Variable Metabolic Priorities for Host Mucosal Glycans. 26556271 11 102 theme behavioral 2806:2815 arg1 dynamics 2817:2824 the behavioral dynamics 2802:2824 the behavioral dynamics of this community 2802:2842 Thus, we reveal new aspects of how individual bacteria, some with otherwise similar metabolic potential, partition to "preferred niches" in the complex gut ecosystem, which has important and immediate implications for understanding and predicting the behavioral dynamics of this community. 26556271 6 103 from Repression 1242:1251 arg1 fragilis 1368:1375 Bacteroides fragilis 1356:1375 Bacteroides fragilis 1356:1375 Repression of mucin glycan-responsive gene clusters in two other human gut bacteria, Bacteroides massiliensis and Bacteroides fragilis, exhibited variable and sometimes reciprocal responses compared to those of B. thetaiotaomicron, revealing that these symbionts vary in their preference for mucin glycans and that these differences occur at the level of controlling individual gene clusters. 26556271 6 103 from Repression 1242:1251 arg1 bacteria 1317:1324 two other human gut bacteria 1297:1324 two other human gut bacteria 1297:1324 Repression of mucin glycan-responsive gene clusters in two other human gut bacteria, Bacteroides massiliensis and Bacteroides fragilis, exhibited variable and sometimes reciprocal responses compared to those of B. thetaiotaomicron, revealing that these symbionts vary in their preference for mucin glycans and that these differences occur at the level of controlling individual gene clusters. 26556271 6 103 from Repression 1242:1251 arg1 massiliensis 1339:1350 Bacteroides massiliensis 1327:1350 Bacteroides massiliensis 1327:1350 Repression of mucin glycan-responsive gene clusters in two other human gut bacteria, Bacteroides massiliensis and Bacteroides fragilis, exhibited variable and sometimes reciprocal responses compared to those of B. thetaiotaomicron, revealing that these symbionts vary in their preference for mucin glycans and that these differences occur at the level of controlling individual gene clusters. 26556271 3 104 theme human 468:472 arg1 thetaiotaomicron 441:456 Bacteroides thetaiotaomicron 429:456 Bacteroides thetaiotaomicron 429:456 We investigated the responses of Bacteroides thetaiotaomicron, a common human intestinal bacterium that metabolizes more than a dozen different polysaccharides, including the O-linked glycans that are abundant in secreted mucin. 26556271 3 104 theme human 468:472 arg1 bacterium 485:493 a common human intestinal bacterium 459:493 a common human intestinal bacterium that metabolizes more than a dozen different polysaccharides, including the O-linked glycans that are abundant in secreted mucin 459:622 We investigated the responses of Bacteroides thetaiotaomicron, a common human intestinal bacterium that metabolizes more than a dozen different polysaccharides, including the O-linked glycans that are abundant in secreted mucin. 26556271 8 105 theme Human 1994:1998 arg1 microorganisms 2011:2024 IMPORTANCE Human intestinal microorganisms 1983:2024 IMPORTANCE Human intestinal microorganisms 1983:2024 IMPORTANCE Human intestinal microorganisms impact many aspects of health and disease, including digestion and the propensity to develop disorders such as inflammation and colon cancer. 26556271 1 106 theme Many 101:104 arg1 bacteria 120:127 UNLABELLED Many symbiotic gut bacteria 90:127 UNLABELLED Many symbiotic gut bacteria 90:127 UNLABELLED Many symbiotic gut bacteria possess the ability to degrade multiple polysaccharides, thereby providing nutritional advantages to their hosts. 26556271 9 107 theme intestinal 2219:2228 arg1 habitat 2230:2236 the intestinal habitat 2215:2236 the intestinal habitat 2215:2236 Complex carbohydrates are a major component of the intestinal habitat, and numerous species have evolved and refined strategies to compete for these coveted nutrients. 26556271 4 108 theme substrates 822:831 arg1 presence 798:805 the presence 794:805 the presence of alternative substrates 794:831 Experiments in which mucin glycans were presented simultaneously with other carbohydrates show that degradation of these host carbohydrates is consistently repressed in the presence of alternative substrates, even by B. thetaiotaomicron previously acclimated to growth in pure mucin glycans. 26556271 0 109 theme Variable 34:41 arg1 Priorities 53:62 Variable Metabolic Priorities 34:62 Variable Metabolic Priorities for Host Mucosal Glycans 34:87 Symbiotic Human Gut Bacteria with Variable Metabolic Priorities for Host Mucosal Glycans. 26556271 11 110 theme community 2834:2842 arg1 dynamics 2817:2824 the behavioral dynamics 2802:2824 the behavioral dynamics of this community 2802:2842 Thus, we reveal new aspects of how individual bacteria, some with otherwise similar metabolic potential, partition to "preferred niches" in the complex gut ecosystem, which has important and immediate implications for understanding and predicting the behavioral dynamics of this community. 26556271 5 111 with Experiments 917:927 arg1 mutants 1003:1009 genetic mutants 995:1009 genetic mutants 995:1009 Experiments with media containing systematically varied carbohydrate cues and genetic mutants reveal that transcriptional repression of genes involved in mucin glycan metabolism is imposed by simple sugars and, in one example that was tested, is mediated through a small intergenic region in a transcript-autonomous fashion. 26556271 5 111 with Experiments 917:927 arg1 media 934:938 media 934:938 media containing systematically varied carbohydrate cues 934:989 Experiments with media containing systematically varied carbohydrate cues and genetic mutants reveal that transcriptional repression of genes involved in mucin glycan metabolism is imposed by simple sugars and, in one example that was tested, is mediated through a small intergenic region in a transcript-autonomous fashion. 26556271 0 112 with Bacteria 20:27 arg1 Priorities 53:62 Variable Metabolic Priorities 34:62 Variable Metabolic Priorities for Host Mucosal Glycans 34:87 Symbiotic Human Gut Bacteria with Variable Metabolic Priorities for Host Mucosal Glycans. 26556271 3 113 theme thetaiotaomicron 441:456 arg1 responses 416:424 the responses 412:424 the responses of Bacteroides thetaiotaomicron, a common human intestinal bacterium that metabolizes more than a dozen different polysaccharides, including the O-linked glycans that are abundant in secreted mucin 412:622 We investigated the responses of Bacteroides thetaiotaomicron, a common human intestinal bacterium that metabolizes more than a dozen different polysaccharides, including the O-linked glycans that are abundant in secreted mucin. 26556271 9 114 theme numerous 2243:2250 arg1 species 2252:2258 numerous species 2243:2258 numerous species 2243:2258 Complex carbohydrates are a major component of the intestinal habitat, and numerous species have evolved and refined strategies to compete for these coveted nutrients. 26556271 4 115 theme mucin 902:906 arg1 glycans 908:914 pure mucin glycans 897:914 pure mucin glycans 897:914 Experiments in which mucin glycans were presented simultaneously with other carbohydrates show that degradation of these host carbohydrates is consistently repressed in the presence of alternative substrates, even by B. thetaiotaomicron previously acclimated to growth in pure mucin glycans. 26556271 6 116 theme gene 1620:1623 arg1 clusters 1625:1632 individual gene clusters 1609:1632 individual gene clusters 1609:1632 Repression of mucin glycan-responsive gene clusters in two other human gut bacteria, Bacteroides massiliensis and Bacteroides fragilis, exhibited variable and sometimes reciprocal responses compared to those of B. thetaiotaomicron, revealing that these symbionts vary in their preference for mucin glycans and that these differences occur at the level of controlling individual gene clusters. 26556271 10 117 theme host 2444:2447 arg1 diet 2449:2452 host diet 2444:2452 host diet 2444:2452 Our findings reveal that individual bacteria exhibit different preferences for carbohydrates emanating from host diet and mucosal secretions and that some of these prioritization strategies are opposite to one another. 26556271 3 118 theme dozen 524:528 arg1 glycans 580:586 the O-linked glycans 567:586 the O-linked glycans that are abundant in secreted mucin 567:622 We investigated the responses of Bacteroides thetaiotaomicron, a common human intestinal bacterium that metabolizes more than a dozen different polysaccharides, including the O-linked glycans that are abundant in secreted mucin. 26556271 3 118 theme dozen 524:528 arg1 polysaccharides 540:554 a dozen different polysaccharides 522:554 a dozen different polysaccharides 522:554 We investigated the responses of Bacteroides thetaiotaomicron, a common human intestinal bacterium that metabolizes more than a dozen different polysaccharides, including the O-linked glycans that are abundant in secreted mucin. 26556271 5 119 theme simple 1109:1114 arg1 sugars 1116:1121 simple sugars 1109:1121 simple sugars 1109:1121 Experiments with media containing systematically varied carbohydrate cues and genetic mutants reveal that transcriptional repression of genes involved in mucin glycan metabolism is imposed by simple sugars and, in one example that was tested, is mediated through a small intergenic region in a transcript-autonomous fashion. 26556271 3 120 theme O-linked 571:578 arg1 glycans 580:586 the O-linked glycans 567:586 the O-linked glycans that are abundant in secreted mucin 567:622 We investigated the responses of Bacteroides thetaiotaomicron, a common human intestinal bacterium that metabolizes more than a dozen different polysaccharides, including the O-linked glycans that are abundant in secreted mucin. 26556271 3 120 theme O-linked 571:578 arg1 abundant 597:604 abundant 597:604 abundant 597:604 We investigated the responses of Bacteroides thetaiotaomicron, a common human intestinal bacterium that metabolizes more than a dozen different polysaccharides, including the O-linked glycans that are abundant in secreted mucin. 28688204 4 0 theme ELISA 932:936 arg1 kit 938:940 a commercial gE ELISA kit 916:940 a commercial gE ELISA kit 916:940 An indirect sandwich enzyme-linked immunosorbent assay (ELISA) was developed using ygEN31-270 as a coating antigen, and the results showed that the assay had high sensitivity and specificity, as well as almost perfect concordance with a commercial gE ELISA kit. 28688204 1 1 theme low-cost 278:285 arg1 protein 227:233 a recombinant pseudorabies virus (PRV) glycoprotein E (gE) protein 168:233 a recombinant pseudorabies virus (PRV) glycoprotein E (gE) protein with the correct antigenicity for use 168:271 AIMS The purpose of this study was to produce a recombinant pseudorabies virus (PRV) glycoprotein E (gE) protein with the correct antigenicity for use as a low-cost diagnostic antigen. 28688204 1 1 theme low-cost 278:285 arg1 antigen 298:304 a low-cost diagnostic antigen 276:304 a low-cost diagnostic antigen 276:304 AIMS The purpose of this study was to produce a recombinant pseudorabies virus (PRV) glycoprotein E (gE) protein with the correct antigenicity for use as a low-cost diagnostic antigen. 28688204 4 2 link enzyme-linked 702:714 arg1 ELISA 737:741 ELISA 737:741 ELISA 737:741 An indirect sandwich enzyme-linked immunosorbent assay (ELISA) was developed using ygEN31-270 as a coating antigen, and the results showed that the assay had high sensitivity and specificity, as well as almost perfect concordance with a commercial gE ELISA kit. 28688204 4 2 link enzyme-linked 702:714 arg1 assay 730:734 An indirect sandwich enzyme-linked immunosorbent assay 681:734 An indirect sandwich enzyme-linked immunosorbent assay (ELISA) 681:742 An indirect sandwich enzyme-linked immunosorbent assay (ELISA) was developed using ygEN31-270 as a coating antigen, and the results showed that the assay had high sensitivity and specificity, as well as almost perfect concordance with a commercial gE ELISA kit. 28688204 4 3 contain had 835:837 arg2 specificity 860:870 specificity 860:870 specificity 860:870 An indirect sandwich enzyme-linked immunosorbent assay (ELISA) was developed using ygEN31-270 as a coating antigen, and the results showed that the assay had high sensitivity and specificity, as well as almost perfect concordance with a commercial gE ELISA kit. 28688204 4 3 contain had 835:837 arg1 assay 829:833 the assay 825:833 the assay 825:833 An indirect sandwich enzyme-linked immunosorbent assay (ELISA) was developed using ygEN31-270 as a coating antigen, and the results showed that the assay had high sensitivity and specificity, as well as almost perfect concordance with a commercial gE ELISA kit. 28688204 4 3 contain had 835:837 arg2 sensitivity 844:854 high sensitivity 839:854 high sensitivity 839:854 An indirect sandwich enzyme-linked immunosorbent assay (ELISA) was developed using ygEN31-270 as a coating antigen, and the results showed that the assay had high sensitivity and specificity, as well as almost perfect concordance with a commercial gE ELISA kit. 28688204 4 3 contain had 835:837 arg2 concordance 899:909 almost perfect concordance 884:909 almost perfect concordance with a commercial gE ELISA kit 884:940 An indirect sandwich enzyme-linked immunosorbent assay (ELISA) was developed using ygEN31-270 as a coating antigen, and the results showed that the assay had high sensitivity and specificity, as well as almost perfect concordance with a commercial gE ELISA kit. 28688204 1 4 theme E 220:220 arg1 protein 227:233 a recombinant pseudorabies virus (PRV) glycoprotein E (gE) protein 168:233 a recombinant pseudorabies virus (PRV) glycoprotein E (gE) protein with the correct antigenicity for use 168:271 AIMS The purpose of this study was to produce a recombinant pseudorabies virus (PRV) glycoprotein E (gE) protein with the correct antigenicity for use as a low-cost diagnostic antigen. 28688204 1 4 theme E 220:220 arg1 antigen 298:304 a low-cost diagnostic antigen 276:304 a low-cost diagnostic antigen 276:304 AIMS The purpose of this study was to produce a recombinant pseudorabies virus (PRV) glycoprotein E (gE) protein with the correct antigenicity for use as a low-cost diagnostic antigen. 28688204 2 5 dep optimized 443:451 arg1 codon 437:441 codon 437:441 codon 437:441 METHODS AND RESULTS The gene fragment encoding the amino-terminal immunodominant region of PRV gE (codons 31-270) (gEN31-270) was codon optimized and expressed constitutively and secreted using a Pichia pastoris expression system. 28688204 0 6 from expression 10:19 arg1 ELISA 115:119 an indirect sandwich ELISA 94:119 an indirect sandwich ELISA 94:119 Enhancing expression of the pseudorabies virus glycoprotein E in yeast and its application in an indirect sandwich ELISA. 28688204 0 6 from expression 10:19 arg1 yeast 65:69 yeast 65:69 yeast 65:69 Enhancing expression of the pseudorabies virus glycoprotein E in yeast and its application in an indirect sandwich ELISA. 28688204 2 7 dep codons 406:411 arg1 31-270 413:418 31-270 413:418 31-270 413:418 METHODS AND RESULTS The gene fragment encoding the amino-terminal immunodominant region of PRV gE (codons 31-270) (gEN31-270) was codon optimized and expressed constitutively and secreted using a Pichia pastoris expression system. 28688204 5 8 theme gE 1005:1006 arg1 region 974:979 The immunodominant region 955:979 CONCLUSIONS The immunodominant region (amino acids 31-270) of gE 943:1006 CONCLUSIONS The immunodominant region (amino acids 31-270) of gE was expressed successfully in P. pastoris using a codon optimization strategy. 28688204 5 8 theme gE 1005:1006 arg1 acids 988:992 amino acids 31-270 982:999 amino acids 31-270 982:999 CONCLUSIONS The immunodominant region (amino acids 31-270) of gE was expressed successfully in P. pastoris using a codon optimization strategy. 28688204 4 9 theme perfect 891:897 arg1 concordance 899:909 almost perfect concordance 884:909 almost perfect concordance with a commercial gE ELISA kit 884:940 An indirect sandwich enzyme-linked immunosorbent assay (ELISA) was developed using ygEN31-270 as a coating antigen, and the results showed that the assay had high sensitivity and specificity, as well as almost perfect concordance with a commercial gE ELISA kit. 28688204 8 10 dep SIGNIFICANCE 1273:1284 arg1 ELISA 1349:1353 The ygEN31-270-based indirect sandwich ELISA 1310:1353 SIGNIFICANCE AND IMPACT OF THE STUDY The ygEN31-270-based indirect sandwich ELISA 1273:1353 SIGNIFICANCE AND IMPACT OF THE STUDY The ygEN31-270-based indirect sandwich ELISA may provide an alternative method for developing a diagnostic kit with easy manipulation and low cost. 28688204 2 11 dep METHODS 307:313 arg1 fragment 336:343 The gene fragment 327:343 The gene fragment encoding the amino-terminal immunodominant region of PRV gE 327:403 METHODS AND RESULTS The gene fragment encoding the amino-terminal immunodominant region of PRV gE (codons 31-270) (gEN31-270) was codon optimized and expressed constitutively and secreted using a Pichia pastoris expression system. 28688204 1 12 theme gE 223:224 arg1 protein 227:233 a recombinant pseudorabies virus (PRV) glycoprotein E (gE) protein 168:233 a recombinant pseudorabies virus (PRV) glycoprotein E (gE) protein with the correct antigenicity for use 168:271 AIMS The purpose of this study was to produce a recombinant pseudorabies virus (PRV) glycoprotein E (gE) protein with the correct antigenicity for use as a low-cost diagnostic antigen. 28688204 1 12 theme gE 223:224 arg1 antigen 298:304 a low-cost diagnostic antigen 276:304 a low-cost diagnostic antigen 276:304 AIMS The purpose of this study was to produce a recombinant pseudorabies virus (PRV) glycoprotein E (gE) protein with the correct antigenicity for use as a low-cost diagnostic antigen. 28688204 1 13 gly glycoprotein 207:218 arg1 glycoprotein 207:218 a recombinant pseudorabies virus (PRV) glycoprotein E (gE) protein 168:233 a recombinant pseudorabies virus (PRV) glycoprotein E (gE) protein with the correct antigenicity for use 168:271 AIMS The purpose of this study was to produce a recombinant pseudorabies virus (PRV) glycoprotein E (gE) protein with the correct antigenicity for use as a low-cost diagnostic antigen. 28688204 1 14 dep AIMS 122:125 arg1 was 153:155 was 153:155 was to produce a recombinant pseudorabies virus (PRV) glycoprotein E (gE) protein with the correct antigenicity for use as a low-cost diagnostic antigen 153:304 AIMS The purpose of this study was to produce a recombinant pseudorabies virus (PRV) glycoprotein E (gE) protein with the correct antigenicity for use as a low-cost diagnostic antigen. 28688204 0 15 theme indirect 97:104 arg1 ELISA 115:119 an indirect sandwich ELISA 94:119 an indirect sandwich ELISA 94:119 Enhancing expression of the pseudorabies virus glycoprotein E in yeast and its application in an indirect sandwich ELISA. 28688204 7 16 theme swine 1252:1256 arg1 samples 1264:1270 swine serum samples 1252:1270 swine serum samples 1252:1270 The ygEN31-270-based indirect sandwich ELISA showed high sensitivity and specificity to detect gE-specific antibodies in swine serum samples. 28688204 2 17 theme immunodominant 373:386 arg1 region 388:393 the amino-terminal immunodominant region 354:393 the amino-terminal immunodominant region of PRV gE 354:403 METHODS AND RESULTS The gene fragment encoding the amino-terminal immunodominant region of PRV gE (codons 31-270) (gEN31-270) was codon optimized and expressed constitutively and secreted using a Pichia pastoris expression system. 28688204 8 18 theme sandwich 1340:1347 arg1 ELISA 1349:1353 The ygEN31-270-based indirect sandwich ELISA 1310:1353 SIGNIFICANCE AND IMPACT OF THE STUDY The ygEN31-270-based indirect sandwich ELISA 1273:1353 SIGNIFICANCE AND IMPACT OF THE STUDY The ygEN31-270-based indirect sandwich ELISA may provide an alternative method for developing a diagnostic kit with easy manipulation and low cost. 28688204 1 19 theme study 147:151 arg1 purpose 131:137 The purpose 127:137 The purpose of this study 127:151 AIMS The purpose of this study was to produce a recombinant pseudorabies virus (PRV) glycoprotein E (gE) protein with the correct antigenicity for use as a low-cost diagnostic antigen. 28688204 7 20 theme indirect 1152:1159 arg1 ELISA 1170:1174 The ygEN31-270-based indirect sandwich ELISA 1131:1174 The ygEN31-270-based indirect sandwich ELISA 1131:1174 The ygEN31-270-based indirect sandwich ELISA showed high sensitivity and specificity to detect gE-specific antibodies in swine serum samples. 28688204 8 21 theme indirect 1331:1338 arg1 ELISA 1349:1353 The ygEN31-270-based indirect sandwich ELISA 1310:1353 SIGNIFICANCE AND IMPACT OF THE STUDY The ygEN31-270-based indirect sandwich ELISA 1273:1353 SIGNIFICANCE AND IMPACT OF THE STUDY The ygEN31-270-based indirect sandwich ELISA may provide an alternative method for developing a diagnostic kit with easy manipulation and low cost. 28688204 2 22 theme gE 402:403 arg1 region 388:393 the amino-terminal immunodominant region 354:393 the amino-terminal immunodominant region of PRV gE 354:403 METHODS AND RESULTS The gene fragment encoding the amino-terminal immunodominant region of PRV gE (codons 31-270) (gEN31-270) was codon optimized and expressed constitutively and secreted using a Pichia pastoris expression system. 28688204 7 23 theme ygEN31-270-based 1135:1150 arg1 ELISA 1170:1174 The ygEN31-270-based indirect sandwich ELISA 1131:1174 The ygEN31-270-based indirect sandwich ELISA 1131:1174 The ygEN31-270-based indirect sandwich ELISA showed high sensitivity and specificity to detect gE-specific antibodies in swine serum samples. 28688204 4 24 theme gE 929:930 arg1 kit 938:940 a commercial gE ELISA kit 916:940 a commercial gE ELISA kit 916:940 An indirect sandwich enzyme-linked immunosorbent assay (ELISA) was developed using ygEN31-270 as a coating antigen, and the results showed that the assay had high sensitivity and specificity, as well as almost perfect concordance with a commercial gE ELISA kit. 28688204 7 25 theme high 1183:1186 arg1 sensitivity 1188:1198 high sensitivity 1183:1198 high sensitivity 1183:1198 The ygEN31-270-based indirect sandwich ELISA showed high sensitivity and specificity to detect gE-specific antibodies in swine serum samples. 28688204 4 26 theme enzyme-linked 702:714 arg1 ELISA 737:741 ELISA 737:741 ELISA 737:741 An indirect sandwich enzyme-linked immunosorbent assay (ELISA) was developed using ygEN31-270 as a coating antigen, and the results showed that the assay had high sensitivity and specificity, as well as almost perfect concordance with a commercial gE ELISA kit. 28688204 4 26 theme enzyme-linked 702:714 arg1 assay 730:734 An indirect sandwich enzyme-linked immunosorbent assay 681:734 An indirect sandwich enzyme-linked immunosorbent assay (ELISA) 681:742 An indirect sandwich enzyme-linked immunosorbent assay (ELISA) was developed using ygEN31-270 as a coating antigen, and the results showed that the assay had high sensitivity and specificity, as well as almost perfect concordance with a commercial gE ELISA kit. 28688204 4 27 theme high 839:842 arg1 sensitivity 844:854 high sensitivity 839:854 high sensitivity 839:854 An indirect sandwich enzyme-linked immunosorbent assay (ELISA) was developed using ygEN31-270 as a coating antigen, and the results showed that the assay had high sensitivity and specificity, as well as almost perfect concordance with a commercial gE ELISA kit. 28688204 2 28 theme gene 331:334 arg1 fragment 336:343 The gene fragment 327:343 The gene fragment encoding the amino-terminal immunodominant region of PRV gE 327:403 METHODS AND RESULTS The gene fragment encoding the amino-terminal immunodominant region of PRV gE (codons 31-270) (gEN31-270) was codon optimized and expressed constitutively and secreted using a Pichia pastoris expression system. 28688204 1 29 theme diagnostic 287:296 arg1 protein 227:233 a recombinant pseudorabies virus (PRV) glycoprotein E (gE) protein 168:233 a recombinant pseudorabies virus (PRV) glycoprotein E (gE) protein with the correct antigenicity for use 168:271 AIMS The purpose of this study was to produce a recombinant pseudorabies virus (PRV) glycoprotein E (gE) protein with the correct antigenicity for use as a low-cost diagnostic antigen. 28688204 1 29 theme diagnostic 287:296 arg1 antigen 298:304 a low-cost diagnostic antigen 276:304 a low-cost diagnostic antigen 276:304 AIMS The purpose of this study was to produce a recombinant pseudorabies virus (PRV) glycoprotein E (gE) protein with the correct antigenicity for use as a low-cost diagnostic antigen. 28688204 1 30 with protein 227:233 arg1 antigenicity 252:263 the correct antigenicity 240:263 the correct antigenicity for use 240:271 AIMS The purpose of this study was to produce a recombinant pseudorabies virus (PRV) glycoprotein E (gE) protein with the correct antigenicity for use as a low-cost diagnostic antigen. 28688204 4 31 theme sandwich 693:700 arg1 ELISA 737:741 ELISA 737:741 ELISA 737:741 An indirect sandwich enzyme-linked immunosorbent assay (ELISA) was developed using ygEN31-270 as a coating antigen, and the results showed that the assay had high sensitivity and specificity, as well as almost perfect concordance with a commercial gE ELISA kit. 28688204 4 31 theme sandwich 693:700 arg1 assay 730:734 An indirect sandwich enzyme-linked immunosorbent assay 681:734 An indirect sandwich enzyme-linked immunosorbent assay (ELISA) 681:742 An indirect sandwich enzyme-linked immunosorbent assay (ELISA) was developed using ygEN31-270 as a coating antigen, and the results showed that the assay had high sensitivity and specificity, as well as almost perfect concordance with a commercial gE ELISA kit. 28688204 4 32 with specificity 860:870 arg1 kit 938:940 a commercial gE ELISA kit 916:940 a commercial gE ELISA kit 916:940 An indirect sandwich enzyme-linked immunosorbent assay (ELISA) was developed using ygEN31-270 as a coating antigen, and the results showed that the assay had high sensitivity and specificity, as well as almost perfect concordance with a commercial gE ELISA kit. 28688204 8 33 theme easy 1426:1429 arg1 manipulation 1431:1442 easy manipulation 1426:1442 easy manipulation 1426:1442 SIGNIFICANCE AND IMPACT OF THE STUDY The ygEN31-270-based indirect sandwich ELISA may provide an alternative method for developing a diagnostic kit with easy manipulation and low cost. 28688204 2 34 theme PRV 398:400 arg1 gE 402:403 PRV gE 398:403 PRV gE 398:403 METHODS AND RESULTS The gene fragment encoding the amino-terminal immunodominant region of PRV gE (codons 31-270) (gEN31-270) was codon optimized and expressed constitutively and secreted using a Pichia pastoris expression system. 28688204 5 35 theme amino 982:986 arg1 region 974:979 The immunodominant region 955:979 CONCLUSIONS The immunodominant region (amino acids 31-270) of gE 943:1006 CONCLUSIONS The immunodominant region (amino acids 31-270) of gE was expressed successfully in P. pastoris using a codon optimization strategy. 28688204 5 35 theme amino 982:986 arg1 acids 988:992 amino acids 31-270 982:999 amino acids 31-270 982:999 CONCLUSIONS The immunodominant region (amino acids 31-270) of gE was expressed successfully in P. pastoris using a codon optimization strategy. 28688204 5 36 theme immunodominant 959:972 arg1 region 974:979 The immunodominant region 955:979 CONCLUSIONS The immunodominant region (amino acids 31-270) of gE 943:1006 CONCLUSIONS The immunodominant region (amino acids 31-270) of gE was expressed successfully in P. pastoris using a codon optimization strategy. 28688204 5 36 theme immunodominant 959:972 arg1 acids 988:992 amino acids 31-270 982:999 amino acids 31-270 982:999 CONCLUSIONS The immunodominant region (amino acids 31-270) of gE was expressed successfully in P. pastoris using a codon optimization strategy. 28688204 5 37 dep CONCLUSIONS 943:953 arg1 region 974:979 The immunodominant region 955:979 CONCLUSIONS The immunodominant region (amino acids 31-270) of gE 943:1006 CONCLUSIONS The immunodominant region (amino acids 31-270) of gE was expressed successfully in P. pastoris using a codon optimization strategy. 28688204 5 37 dep CONCLUSIONS 943:953 arg1 acids 988:992 amino acids 31-270 982:999 amino acids 31-270 982:999 CONCLUSIONS The immunodominant region (amino acids 31-270) of gE was expressed successfully in P. pastoris using a codon optimization strategy. 28688204 5 38 theme codon 1058:1062 arg1 strategy 1077:1084 a codon optimization strategy 1056:1084 a codon optimization strategy 1056:1084 CONCLUSIONS The immunodominant region (amino acids 31-270) of gE was expressed successfully in P. pastoris using a codon optimization strategy. 28688204 0 39 theme sandwich 106:113 arg1 ELISA 115:119 an indirect sandwich ELISA 94:119 an indirect sandwich ELISA 94:119 Enhancing expression of the pseudorabies virus glycoprotein E in yeast and its application in an indirect sandwich ELISA. 28688204 3 40 theme culture 600:606 arg1 supernatant 608:618 the culture supernatant 596:618 the culture supernatant 596:618 Yeast-expressed gEN31-270 (ygEN31-270) was harvested from the culture supernatant, and ygEN31-270 was shown to exhibit N-linked glycosylation. 28688204 4 41 theme immunosorbent 716:728 arg1 ELISA 737:741 ELISA 737:741 ELISA 737:741 An indirect sandwich enzyme-linked immunosorbent assay (ELISA) was developed using ygEN31-270 as a coating antigen, and the results showed that the assay had high sensitivity and specificity, as well as almost perfect concordance with a commercial gE ELISA kit. 28688204 4 41 theme immunosorbent 716:728 arg1 assay 730:734 An indirect sandwich enzyme-linked immunosorbent assay 681:734 An indirect sandwich enzyme-linked immunosorbent assay (ELISA) 681:742 An indirect sandwich enzyme-linked immunosorbent assay (ELISA) was developed using ygEN31-270 as a coating antigen, and the results showed that the assay had high sensitivity and specificity, as well as almost perfect concordance with a commercial gE ELISA kit. 28688204 4 42 with sensitivity 844:854 arg1 kit 938:940 a commercial gE ELISA kit 916:940 a commercial gE ELISA kit 916:940 An indirect sandwich enzyme-linked immunosorbent assay (ELISA) was developed using ygEN31-270 as a coating antigen, and the results showed that the assay had high sensitivity and specificity, as well as almost perfect concordance with a commercial gE ELISA kit. 28688204 1 43 theme recombinant 170:180 arg1 protein 227:233 a recombinant pseudorabies virus (PRV) glycoprotein E (gE) protein 168:233 a recombinant pseudorabies virus (PRV) glycoprotein E (gE) protein with the correct antigenicity for use 168:271 AIMS The purpose of this study was to produce a recombinant pseudorabies virus (PRV) glycoprotein E (gE) protein with the correct antigenicity for use as a low-cost diagnostic antigen. 28688204 1 43 theme recombinant 170:180 arg1 antigen 298:304 a low-cost diagnostic antigen 276:304 a low-cost diagnostic antigen 276:304 AIMS The purpose of this study was to produce a recombinant pseudorabies virus (PRV) glycoprotein E (gE) protein with the correct antigenicity for use as a low-cost diagnostic antigen. 28688204 0 44 theme virus 41:45 arg1 E 60:60 the pseudorabies virus glycoprotein E 24:60 the pseudorabies virus glycoprotein E 24:60 Enhancing expression of the pseudorabies virus glycoprotein E in yeast and its application in an indirect sandwich ELISA. 28688204 1 45 theme correct 244:250 arg1 antigenicity 252:263 the correct antigenicity 240:263 the correct antigenicity for use 240:271 AIMS The purpose of this study was to produce a recombinant pseudorabies virus (PRV) glycoprotein E (gE) protein with the correct antigenicity for use as a low-cost diagnostic antigen. 28688204 2 46 theme amino-terminal 358:371 arg1 region 388:393 the amino-terminal immunodominant region 354:393 the amino-terminal immunodominant region of PRV gE 354:403 METHODS AND RESULTS The gene fragment encoding the amino-terminal immunodominant region of PRV gE (codons 31-270) (gEN31-270) was codon optimized and expressed constitutively and secreted using a Pichia pastoris expression system. 28688204 4 47 theme coating 780:786 arg1 ygEN31-270 764:773 ygEN31-270 764:773 ygEN31-270 764:773 An indirect sandwich enzyme-linked immunosorbent assay (ELISA) was developed using ygEN31-270 as a coating antigen, and the results showed that the assay had high sensitivity and specificity, as well as almost perfect concordance with a commercial gE ELISA kit. 28688204 4 47 theme coating 780:786 arg1 antigen 788:794 a coating antigen 778:794 a coating antigen 778:794 An indirect sandwich enzyme-linked immunosorbent assay (ELISA) was developed using ygEN31-270 as a coating antigen, and the results showed that the assay had high sensitivity and specificity, as well as almost perfect concordance with a commercial gE ELISA kit. 28688204 3 48 link N-linked 657:664 arg1 glycosylation 666:678 N-linked glycosylation 657:678 N-linked glycosylation 657:678 Yeast-expressed gEN31-270 (ygEN31-270) was harvested from the culture supernatant, and ygEN31-270 was shown to exhibit N-linked glycosylation. 28688204 1 49 theme pseudorabies 182:193 arg1 protein 227:233 a recombinant pseudorabies virus (PRV) glycoprotein E (gE) protein 168:233 a recombinant pseudorabies virus (PRV) glycoprotein E (gE) protein with the correct antigenicity for use 168:271 AIMS The purpose of this study was to produce a recombinant pseudorabies virus (PRV) glycoprotein E (gE) protein with the correct antigenicity for use as a low-cost diagnostic antigen. 28688204 1 49 theme pseudorabies 182:193 arg1 antigen 298:304 a low-cost diagnostic antigen 276:304 a low-cost diagnostic antigen 276:304 AIMS The purpose of this study was to produce a recombinant pseudorabies virus (PRV) glycoprotein E (gE) protein with the correct antigenicity for use as a low-cost diagnostic antigen. 28688204 0 50 theme pseudorabies 28:39 arg1 E 60:60 the pseudorabies virus glycoprotein E 24:60 the pseudorabies virus glycoprotein E 24:60 Enhancing expression of the pseudorabies virus glycoprotein E in yeast and its application in an indirect sandwich ELISA. 28688204 8 51 with kit 1417:1419 arg1 manipulation 1431:1442 easy manipulation 1426:1442 easy manipulation 1426:1442 SIGNIFICANCE AND IMPACT OF THE STUDY The ygEN31-270-based indirect sandwich ELISA may provide an alternative method for developing a diagnostic kit with easy manipulation and low cost. 28688204 8 51 with kit 1417:1419 arg1 cost 1452:1455 low cost 1448:1455 low cost 1448:1455 SIGNIFICANCE AND IMPACT OF THE STUDY The ygEN31-270-based indirect sandwich ELISA may provide an alternative method for developing a diagnostic kit with easy manipulation and low cost. 28688204 8 52 theme low 1448:1450 arg1 cost 1452:1455 low cost 1448:1455 low cost 1448:1455 SIGNIFICANCE AND IMPACT OF THE STUDY The ygEN31-270-based indirect sandwich ELISA may provide an alternative method for developing a diagnostic kit with easy manipulation and low cost. 28688204 8 53 theme alternative 1370:1380 arg1 method 1382:1387 an alternative method 1367:1387 an alternative method for developing a diagnostic kit with easy manipulation and low cost 1367:1455 SIGNIFICANCE AND IMPACT OF THE STUDY The ygEN31-270-based indirect sandwich ELISA may provide an alternative method for developing a diagnostic kit with easy manipulation and low cost. 28688204 1 54 theme virus 195:199 arg1 protein 227:233 a recombinant pseudorabies virus (PRV) glycoprotein E (gE) protein 168:233 a recombinant pseudorabies virus (PRV) glycoprotein E (gE) protein with the correct antigenicity for use 168:271 AIMS The purpose of this study was to produce a recombinant pseudorabies virus (PRV) glycoprotein E (gE) protein with the correct antigenicity for use as a low-cost diagnostic antigen. 28688204 1 54 theme virus 195:199 arg1 antigen 298:304 a low-cost diagnostic antigen 276:304 a low-cost diagnostic antigen 276:304 AIMS The purpose of this study was to produce a recombinant pseudorabies virus (PRV) glycoprotein E (gE) protein with the correct antigenicity for use as a low-cost diagnostic antigen. 28688204 0 55 theme E 60:60 arg1 expression 10:19 expression 10:19 expression of the pseudorabies virus glycoprotein E in yeast 10:69 Enhancing expression of the pseudorabies virus glycoprotein E in yeast and its application in an indirect sandwich ELISA. 28688204 0 55 theme E 60:60 arg1 application 79:89 its application 75:89 its application in an indirect sandwich ELISA 75:119 Enhancing expression of the pseudorabies virus glycoprotein E in yeast and its application in an indirect sandwich ELISA. 28688204 7 56 theme sandwich 1161:1168 arg1 ELISA 1170:1174 The ygEN31-270-based indirect sandwich ELISA 1131:1174 The ygEN31-270-based indirect sandwich ELISA 1131:1174 The ygEN31-270-based indirect sandwich ELISA showed high sensitivity and specificity to detect gE-specific antibodies in swine serum samples. 28688204 5 57 theme optimization 1064:1075 arg1 strategy 1077:1084 a codon optimization strategy 1056:1084 a codon optimization strategy 1056:1084 CONCLUSIONS The immunodominant region (amino acids 31-270) of gE was expressed successfully in P. pastoris using a codon optimization strategy. 28688204 0 58 theme glycoprotein 47:58 arg1 E 60:60 the pseudorabies virus glycoprotein E 24:60 the pseudorabies virus glycoprotein E 24:60 Enhancing expression of the pseudorabies virus glycoprotein E in yeast and its application in an indirect sandwich ELISA. 28688204 2 59 theme expression 519:528 arg1 system 530:535 a Pichia pastoris expression system 501:535 a Pichia pastoris expression system 501:535 METHODS AND RESULTS The gene fragment encoding the amino-terminal immunodominant region of PRV gE (codons 31-270) (gEN31-270) was codon optimized and expressed constitutively and secreted using a Pichia pastoris expression system. 28688204 3 60 theme Yeast-expressed 538:552 arg1 gEN31-270 554:562 Yeast-expressed gEN31-270 538:562 Yeast-expressed gEN31-270 (ygEN31-270) 538:575 Yeast-expressed gEN31-270 (ygEN31-270) was harvested from the culture supernatant, and ygEN31-270 was shown to exhibit N-linked glycosylation. 28688204 3 60 theme Yeast-expressed 538:552 arg1 ygEN31-270 565:574 ygEN31-270 565:574 ygEN31-270 565:574 Yeast-expressed gEN31-270 (ygEN31-270) was harvested from the culture supernatant, and ygEN31-270 was shown to exhibit N-linked glycosylation. 28688204 7 61 theme serum 1258:1262 arg1 samples 1264:1270 swine serum samples 1252:1270 swine serum samples 1252:1270 The ygEN31-270-based indirect sandwich ELISA showed high sensitivity and specificity to detect gE-specific antibodies in swine serum samples. 28688204 8 62 theme diagnostic 1406:1415 arg1 kit 1417:1419 a diagnostic kit 1404:1419 a diagnostic kit with easy manipulation and low cost 1404:1455 SIGNIFICANCE AND IMPACT OF THE STUDY The ygEN31-270-based indirect sandwich ELISA may provide an alternative method for developing a diagnostic kit with easy manipulation and low cost. 28688204 4 63 theme indirect 684:691 arg1 ELISA 737:741 ELISA 737:741 ELISA 737:741 An indirect sandwich enzyme-linked immunosorbent assay (ELISA) was developed using ygEN31-270 as a coating antigen, and the results showed that the assay had high sensitivity and specificity, as well as almost perfect concordance with a commercial gE ELISA kit. 28688204 4 63 theme indirect 684:691 arg1 assay 730:734 An indirect sandwich enzyme-linked immunosorbent assay 681:734 An indirect sandwich enzyme-linked immunosorbent assay (ELISA) 681:742 An indirect sandwich enzyme-linked immunosorbent assay (ELISA) was developed using ygEN31-270 as a coating antigen, and the results showed that the assay had high sensitivity and specificity, as well as almost perfect concordance with a commercial gE ELISA kit. 28688204 2 64 theme Pichia 503:508 arg1 system 530:535 a Pichia pastoris expression system 501:535 a Pichia pastoris expression system 501:535 METHODS AND RESULTS The gene fragment encoding the amino-terminal immunodominant region of PRV gE (codons 31-270) (gEN31-270) was codon optimized and expressed constitutively and secreted using a Pichia pastoris expression system. 28688204 8 65 theme ygEN31-270-based 1314:1329 arg1 ELISA 1349:1353 The ygEN31-270-based indirect sandwich ELISA 1310:1353 SIGNIFICANCE AND IMPACT OF THE STUDY The ygEN31-270-based indirect sandwich ELISA 1273:1353 SIGNIFICANCE AND IMPACT OF THE STUDY The ygEN31-270-based indirect sandwich ELISA may provide an alternative method for developing a diagnostic kit with easy manipulation and low cost. 28688204 8 66 theme STUDY 1304:1308 arg1 SIGNIFICANCE 1273:1284 SIGNIFICANCE 1273:1284 SIGNIFICANCE 1273:1284 SIGNIFICANCE AND IMPACT OF THE STUDY The ygEN31-270-based indirect sandwich ELISA may provide an alternative method for developing a diagnostic kit with easy manipulation and low cost. 28688204 8 66 theme STUDY 1304:1308 arg1 IMPACT 1290:1295 IMPACT 1290:1295 IMPACT 1290:1295 SIGNIFICANCE AND IMPACT OF THE STUDY The ygEN31-270-based indirect sandwich ELISA may provide an alternative method for developing a diagnostic kit with easy manipulation and low cost. 28688204 1 67 theme PRV 202:204 arg1 protein 227:233 a recombinant pseudorabies virus (PRV) glycoprotein E (gE) protein 168:233 a recombinant pseudorabies virus (PRV) glycoprotein E (gE) protein with the correct antigenicity for use 168:271 AIMS The purpose of this study was to produce a recombinant pseudorabies virus (PRV) glycoprotein E (gE) protein with the correct antigenicity for use as a low-cost diagnostic antigen. 28688204 1 67 theme PRV 202:204 arg1 antigen 298:304 a low-cost diagnostic antigen 276:304 a low-cost diagnostic antigen 276:304 AIMS The purpose of this study was to produce a recombinant pseudorabies virus (PRV) glycoprotein E (gE) protein with the correct antigenicity for use as a low-cost diagnostic antigen. 28688204 4 68 theme commercial 918:927 arg1 kit 938:940 a commercial gE ELISA kit 916:940 a commercial gE ELISA kit 916:940 An indirect sandwich enzyme-linked immunosorbent assay (ELISA) was developed using ygEN31-270 as a coating antigen, and the results showed that the assay had high sensitivity and specificity, as well as almost perfect concordance with a commercial gE ELISA kit. 28688204 0 69 from application 79:89 arg1 ELISA 115:119 an indirect sandwich ELISA 94:119 an indirect sandwich ELISA 94:119 Enhancing expression of the pseudorabies virus glycoprotein E in yeast and its application in an indirect sandwich ELISA. 28688204 0 69 from application 79:89 arg1 yeast 65:69 yeast 65:69 yeast 65:69 Enhancing expression of the pseudorabies virus glycoprotein E in yeast and its application in an indirect sandwich ELISA. 28688204 0 70 gly glycoprotein 47:58 arg1 glycoprotein 47:58 the pseudorabies virus glycoprotein E 24:60 the pseudorabies virus glycoprotein E 24:60 Enhancing expression of the pseudorabies virus glycoprotein E in yeast and its application in an indirect sandwich ELISA. 28688204 4 71 with concordance 899:909 arg1 kit 938:940 a commercial gE ELISA kit 916:940 a commercial gE ELISA kit 916:940 An indirect sandwich enzyme-linked immunosorbent assay (ELISA) was developed using ygEN31-270 as a coating antigen, and the results showed that the assay had high sensitivity and specificity, as well as almost perfect concordance with a commercial gE ELISA kit. 28688204 2 72 dep Pichia 503:508 arg1 pastoris 510:517 pastoris 510:517 pastoris 510:517 METHODS AND RESULTS The gene fragment encoding the amino-terminal immunodominant region of PRV gE (codons 31-270) (gEN31-270) was codon optimized and expressed constitutively and secreted using a Pichia pastoris expression system. 28688204 3 73 theme N-linked 657:664 arg1 glycosylation 666:678 N-linked glycosylation 657:678 N-linked glycosylation 657:678 Yeast-expressed gEN31-270 (ygEN31-270) was harvested from the culture supernatant, and ygEN31-270 was shown to exhibit N-linked glycosylation. 28688204 7 74 theme gE-specific 1226:1236 arg1 antibodies 1238:1247 gE-specific antibodies 1226:1247 gE-specific antibodies 1226:1247 The ygEN31-270-based indirect sandwich ELISA showed high sensitivity and specificity to detect gE-specific antibodies in swine serum samples. 28688204 1 75 theme glycoprotein 207:218 arg1 protein 227:233 a recombinant pseudorabies virus (PRV) glycoprotein E (gE) protein 168:233 a recombinant pseudorabies virus (PRV) glycoprotein E (gE) protein with the correct antigenicity for use 168:271 AIMS The purpose of this study was to produce a recombinant pseudorabies virus (PRV) glycoprotein E (gE) protein with the correct antigenicity for use as a low-cost diagnostic antigen. 28688204 1 75 theme glycoprotein 207:218 arg1 antigen 298:304 a low-cost diagnostic antigen 276:304 a low-cost diagnostic antigen 276:304 AIMS The purpose of this study was to produce a recombinant pseudorabies virus (PRV) glycoprotein E (gE) protein with the correct antigenicity for use as a low-cost diagnostic antigen. 28428079 12 0 theme inhibitory 2138:2147 arg1 OPN 2159:2161 crosslinked inhibitory polymeric OPN 2126:2161 crosslinked inhibitory polymeric OPN near the mineralization front 2126:2191 These results suggest that in bone, the increased size and branched structure of crosslinked inhibitory polymeric OPN near the mineralization front could hinder it from accessing focal mineralization sites in the dense collagen-rich matrix, suggesting that OPN-crosslinking into polymers may represent a way to fine-tune the inhibitory potency of OPN on bone mineralization. 28428079 10 1 theme polymeric 1586:1594 arg1 OPN 1596:1598 this exogenous polymeric OPN 1571:1598 this exogenous polymeric OPN 1571:1598 When added to MC3T3-E1 osteoblast cultures, this exogenous polymeric OPN essentially did not inhibit mineralization when given during the later mineralization stages of culture; however, cultures treated early and then continuously with polymeric OPN throughout both the matrix assembly and mineral deposition stages showed reduced mineralization. 28428079 3 2 theme glutamine 526:534 arg1 residues 547:554 glutamine and lysine residues 526:554 residues 547:554 In bone, OPN exists both as a monomer and as a high-molecular-weight polymer - the latter is formed by transglutaminase-mediated crosslinking of glutamine and lysine residues in OPN to create homotypic protein assemblies. 28428079 8 3 theme polymeric 1174:1182 arg1 form 1184:1187 its polymeric form 1170:1187 its polymeric form 1170:1187 In cell-free conditions, TG2 was used to crosslink bovine OPN into its polymeric form, and atomic force microscopy and dynamic light scattering revealed variably-sized, large branched aggregates ranging across hundreds of nanometers. 28428079 6 4 theme OPN 904:906 arg1 effect 882:887 the effect 878:887 the effect of polymerized OPN on mineralization 878:924 In this study, we investigated the effect of polymerized OPN on mineralization using a hydroxyapatite crystal growth assay and mineralizing MC3T3-E1 osteoblast cultures. 28428079 10 5 theme mineral 1818:1824 arg1 deposition 1826:1835 mineral deposition 1818:1835 mineral deposition 1818:1835 When added to MC3T3-E1 osteoblast cultures, this exogenous polymeric OPN essentially did not inhibit mineralization when given during the later mineralization stages of culture; however, cultures treated early and then continuously with polymeric OPN throughout both the matrix assembly and mineral deposition stages showed reduced mineralization. 28428079 12 6 theme branched 2104:2111 arg1 structure 2113:2121 branched structure 2104:2121 branched structure 2104:2121 These results suggest that in bone, the increased size and branched structure of crosslinked inhibitory polymeric OPN near the mineralization front could hinder it from accessing focal mineralization sites in the dense collagen-rich matrix, suggesting that OPN-crosslinking into polymers may represent a way to fine-tune the inhibitory potency of OPN on bone mineralization. 28428079 8 7 theme variably-sized 1256:1269 arg1 aggregates 1287:1296 variably-sized, large branched aggregates 1256:1296 aggregates 1287:1296 In cell-free conditions, TG2 was used to crosslink bovine OPN into its polymeric form, and atomic force microscopy and dynamic light scattering revealed variably-sized, large branched aggregates ranging across hundreds of nanometers. 28428079 2 8 theme matrix 287:292 arg1 mineralization 294:307 matrix mineralization 287:307 matrix mineralization 287:307 OPN is a well-known inhibitor of matrix mineralization, and enzymatic modification of OPN can affect this inhibitory function. 28428079 1 9 theme mineral-binding 196:210 arg1 proteins 219:226 mineral-binding matrix proteins 196:226 mineral-binding matrix proteins found in bones and teeth 196:251 Osteopontin (OPN) belongs to the SIBLING family (Small, Integrin-Binding LIgand N-linked Glycoproteins) of mineral-binding matrix proteins found in bones and teeth. 28428079 8 10 theme atomic 1194:1199 arg1 microscopy 1207:1216 atomic force microscopy 1194:1216 atomic force microscopy 1194:1216 In cell-free conditions, TG2 was used to crosslink bovine OPN into its polymeric form, and atomic force microscopy and dynamic light scattering revealed variably-sized, large branched aggregates ranging across hundreds of nanometers. 28428079 8 11 theme large 1272:1276 arg1 aggregates 1287:1296 variably-sized, large branched aggregates 1256:1296 aggregates 1287:1296 In cell-free conditions, TG2 was used to crosslink bovine OPN into its polymeric form, and atomic force microscopy and dynamic light scattering revealed variably-sized, large branched aggregates ranging across hundreds of nanometers. 28428079 10 12 theme reduced 1851:1857 arg1 mineralization 1859:1872 reduced mineralization 1851:1872 reduced mineralization 1851:1872 When added to MC3T3-E1 osteoblast cultures, this exogenous polymeric OPN essentially did not inhibit mineralization when given during the later mineralization stages of culture; however, cultures treated early and then continuously with polymeric OPN throughout both the matrix assembly and mineral deposition stages showed reduced mineralization. 28428079 1 13 theme proteins 219:226 arg1 Glycoproteins 178:190 Small, Integrin-Binding LIgand N-linked Glycoproteins 138:190 Small, Integrin-Binding LIgand N-linked Glycoproteins 138:190 Osteopontin (OPN) belongs to the SIBLING family (Small, Integrin-Binding LIgand N-linked Glycoproteins) of mineral-binding matrix proteins found in bones and teeth. 28428079 1 13 theme proteins 219:226 arg1 family 130:135 the SIBLING family 118:135 the SIBLING family (Small, Integrin-Binding LIgand N-linked Glycoproteins) of mineral-binding matrix proteins found in bones and teeth 118:251 Osteopontin (OPN) belongs to the SIBLING family (Small, Integrin-Binding LIgand N-linked Glycoproteins) of mineral-binding matrix proteins found in bones and teeth. 28428079 6 14 theme mineralizing 974:985 arg1 cultures 1007:1014 mineralizing MC3T3-E1 osteoblast cultures 974:1014 mineralizing MC3T3-E1 osteoblast cultures 974:1014 In this study, we investigated the effect of polymerized OPN on mineralization using a hydroxyapatite crystal growth assay and mineralizing MC3T3-E1 osteoblast cultures. 28428079 3 15 theme homotypic 573:581 arg1 assemblies 591:600 homotypic protein assemblies 573:600 homotypic protein assemblies 573:600 In bone, OPN exists both as a monomer and as a high-molecular-weight polymer - the latter is formed by transglutaminase-mediated crosslinking of glutamine and lysine residues in OPN to create homotypic protein assemblies. 28428079 8 16 theme dynamic 1222:1228 arg1 scattering 1236:1245 dynamic light scattering 1222:1245 dynamic light scattering 1222:1245 In cell-free conditions, TG2 was used to crosslink bovine OPN into its polymeric form, and atomic force microscopy and dynamic light scattering revealed variably-sized, large branched aggregates ranging across hundreds of nanometers. 28428079 12 17 theme focal 2224:2228 arg1 sites 2245:2249 focal mineralization sites 2224:2249 focal mineralization sites 2224:2249 These results suggest that in bone, the increased size and branched structure of crosslinked inhibitory polymeric OPN near the mineralization front could hinder it from accessing focal mineralization sites in the dense collagen-rich matrix, suggesting that OPN-crosslinking into polymers may represent a way to fine-tune the inhibitory potency of OPN on bone mineralization. 28428079 6 18 theme crystal 949:955 arg1 assay 964:968 a hydroxyapatite crystal growth assay 932:968 a hydroxyapatite crystal growth assay 932:968 In this study, we investigated the effect of polymerized OPN on mineralization using a hydroxyapatite crystal growth assay and mineralizing MC3T3-E1 osteoblast cultures. 28428079 10 19 theme mineralization 1671:1684 arg1 stages 1686:1691 the later mineralization stages 1661:1691 the later mineralization stages of culture 1661:1702 When added to MC3T3-E1 osteoblast cultures, this exogenous polymeric OPN essentially did not inhibit mineralization when given during the later mineralization stages of culture; however, cultures treated early and then continuously with polymeric OPN throughout both the matrix assembly and mineral deposition stages showed reduced mineralization. 28428079 11 20 theme extracts 1901:1908 arg1 Immunoblotting 1875:1888 Immunoblotting 1875:1888 Immunoblotting of protein extracts from these continuously treated cultures 1875:1949 Immunoblotting of protein extracts from these continuously treated cultures revealed exogenous OPN polymers incorporated into mature matrix that had not yet mineralized. 28428079 1 21 theme Small 138:142 arg1 Glycoproteins 178:190 Small, Integrin-Binding LIgand N-linked Glycoproteins 138:190 Small, Integrin-Binding LIgand N-linked Glycoproteins 138:190 Osteopontin (OPN) belongs to the SIBLING family (Small, Integrin-Binding LIgand N-linked Glycoproteins) of mineral-binding matrix proteins found in bones and teeth. 28428079 1 21 theme Small 138:142 arg1 family 130:135 the SIBLING family 118:135 the SIBLING family (Small, Integrin-Binding LIgand N-linked Glycoproteins) of mineral-binding matrix proteins found in bones and teeth 118:251 Osteopontin (OPN) belongs to the SIBLING family (Small, Integrin-Binding LIgand N-linked Glycoproteins) of mineral-binding matrix proteins found in bones and teeth. 28428079 5 22 theme increased 702:710 arg1 binding 712:718 increased binding 702:718 increased binding to collagen 702:730 Polymeric OPN has increased binding to collagen and promotes osteoblast adhesion, but despite these initial observations, its role in mineralization is not clear. 28428079 12 23 theme OPN 2159:2161 arg1 size 2095:2098 the increased size 2081:2098 the increased size 2081:2098 These results suggest that in bone, the increased size and branched structure of crosslinked inhibitory polymeric OPN near the mineralization front could hinder it from accessing focal mineralization sites in the dense collagen-rich matrix, suggesting that OPN-crosslinking into polymers may represent a way to fine-tune the inhibitory potency of OPN on bone mineralization. 28428079 12 23 theme OPN 2159:2161 arg1 structure 2113:2121 branched structure 2104:2121 branched structure 2104:2121 These results suggest that in bone, the increased size and branched structure of crosslinked inhibitory polymeric OPN near the mineralization front could hinder it from accessing focal mineralization sites in the dense collagen-rich matrix, suggesting that OPN-crosslinking into polymers may represent a way to fine-tune the inhibitory potency of OPN on bone mineralization. 28428079 1 24 theme N-linked 169:176 arg1 Glycoproteins 178:190 Small, Integrin-Binding LIgand N-linked Glycoproteins 138:190 Small, Integrin-Binding LIgand N-linked Glycoproteins 138:190 Osteopontin (OPN) belongs to the SIBLING family (Small, Integrin-Binding LIgand N-linked Glycoproteins) of mineral-binding matrix proteins found in bones and teeth. 28428079 1 24 theme N-linked 169:176 arg1 family 130:135 the SIBLING family 118:135 the SIBLING family (Small, Integrin-Binding LIgand N-linked Glycoproteins) of mineral-binding matrix proteins found in bones and teeth 118:251 Osteopontin (OPN) belongs to the SIBLING family (Small, Integrin-Binding LIgand N-linked Glycoproteins) of mineral-binding matrix proteins found in bones and teeth. 28428079 12 25 theme increased 2085:2093 arg1 size 2095:2098 the increased size 2081:2098 the increased size 2081:2098 These results suggest that in bone, the increased size and branched structure of crosslinked inhibitory polymeric OPN near the mineralization front could hinder it from accessing focal mineralization sites in the dense collagen-rich matrix, suggesting that OPN-crosslinking into polymers may represent a way to fine-tune the inhibitory potency of OPN on bone mineralization. 28428079 5 26 theme initial 784:790 arg1 observations 792:803 these initial observations 778:803 these initial observations 778:803 Polymeric OPN has increased binding to collagen and promotes osteoblast adhesion, but despite these initial observations, its role in mineralization is not clear. 28428079 5 27 theme osteoblast 745:754 arg1 adhesion 756:763 osteoblast adhesion 745:763 osteoblast adhesion 745:763 Polymeric OPN has increased binding to collagen and promotes osteoblast adhesion, but despite these initial observations, its role in mineralization is not clear. 28428079 6 28 theme osteoblast 996:1005 arg1 cultures 1007:1014 mineralizing MC3T3-E1 osteoblast cultures 974:1014 mineralizing MC3T3-E1 osteoblast cultures 974:1014 In this study, we investigated the effect of polymerized OPN on mineralization using a hydroxyapatite crystal growth assay and mineralizing MC3T3-E1 osteoblast cultures. 28428079 12 29 theme inhibitory 2370:2379 arg1 potency 2381:2387 the inhibitory potency 2366:2387 the inhibitory potency of OPN 2366:2394 These results suggest that in bone, the increased size and branched structure of crosslinked inhibitory polymeric OPN near the mineralization front could hinder it from accessing focal mineralization sites in the dense collagen-rich matrix, suggesting that OPN-crosslinking into polymers may represent a way to fine-tune the inhibitory potency of OPN on bone mineralization. 28428079 3 30 theme high-molecular-weight 428:448 arg1 polymer 450:456 a high-molecular-weight polymer 426:456 a high-molecular-weight polymer 426:456 In bone, OPN exists both as a monomer and as a high-molecular-weight polymer - the latter is formed by transglutaminase-mediated crosslinking of glutamine and lysine residues in OPN to create homotypic protein assemblies. 28428079 11 31 from cultures 1942:1949 arg1 Immunoblotting 1875:1888 Immunoblotting 1875:1888 Immunoblotting of protein extracts from these continuously treated cultures 1875:1949 Immunoblotting of protein extracts from these continuously treated cultures revealed exogenous OPN polymers incorporated into mature matrix that had not yet mineralized. 28428079 11 31 from cultures 1942:1949 arg1 extracts 1901:1908 protein extracts 1893:1908 protein extracts from these continuously treated cultures 1893:1949 Immunoblotting of protein extracts from these continuously treated cultures revealed exogenous OPN polymers incorporated into mature matrix that had not yet mineralized. 28428079 11 32 theme mature 2001:2006 arg1 matrix 2008:2013 mature matrix 2001:2013 mature matrix that had not yet mineralized 2001:2042 Immunoblotting of protein extracts from these continuously treated cultures revealed exogenous OPN polymers incorporated into mature matrix that had not yet mineralized. 28428079 0 33 theme Mineralization-inhibiting 0:24 arg1 effects 26:32 Mineralization-inhibiting effects 0:32 Mineralization-inhibiting effects of transglutaminase-crosslinked polymeric osteopontin 0:86 Mineralization-inhibiting effects of transglutaminase-crosslinked polymeric osteopontin. 28428079 9 34 from growth 1370:1375 arg1 solution 1407:1414 solution 1407:1414 solution 1407:1414 These OPN polymers inhibited the growth of hydroxyapatite crystals in solution at concentrations similar to monomeric OPN, although the crosslinking slightly reduced its inhibitory potency. 28428079 10 35 theme osteoblast 1550:1559 arg1 cultures 1561:1568 MC3T3-E1 osteoblast cultures 1541:1568 MC3T3-E1 osteoblast cultures 1541:1568 When added to MC3T3-E1 osteoblast cultures, this exogenous polymeric OPN essentially did not inhibit mineralization when given during the later mineralization stages of culture; however, cultures treated early and then continuously with polymeric OPN throughout both the matrix assembly and mineral deposition stages showed reduced mineralization. 28428079 3 36 theme residues 547:554 arg1 crosslinking 510:521 transglutaminase-mediated crosslinking 484:521 transglutaminase-mediated crosslinking of glutamine and lysine residues 484:554 In bone, OPN exists both as a monomer and as a high-molecular-weight polymer - the latter is formed by transglutaminase-mediated crosslinking of glutamine and lysine residues in OPN to create homotypic protein assemblies. 28428079 1 37 theme LIgand 162:167 arg1 Glycoproteins 178:190 Small, Integrin-Binding LIgand N-linked Glycoproteins 138:190 Small, Integrin-Binding LIgand N-linked Glycoproteins 138:190 Osteopontin (OPN) belongs to the SIBLING family (Small, Integrin-Binding LIgand N-linked Glycoproteins) of mineral-binding matrix proteins found in bones and teeth. 28428079 1 37 theme LIgand 162:167 arg1 family 130:135 the SIBLING family 118:135 the SIBLING family (Small, Integrin-Binding LIgand N-linked Glycoproteins) of mineral-binding matrix proteins found in bones and teeth 118:251 Osteopontin (OPN) belongs to the SIBLING family (Small, Integrin-Binding LIgand N-linked Glycoproteins) of mineral-binding matrix proteins found in bones and teeth. 28428079 8 38 used used 1136:1139 arg2 TG2 1128:1130 TG2 1128:1130 TG2 1128:1130 In cell-free conditions, TG2 was used to crosslink bovine OPN into its polymeric form, and atomic force microscopy and dynamic light scattering revealed variably-sized, large branched aggregates ranging across hundreds of nanometers. 28428079 4 39 theme Factor 669:674 arg1 XIII-A 676:681 Factor XIII-A 669:681 Factor XIII-A 669:681 OPN can be covalently crosslinked by transglutaminase 2 (TG2) and Factor XIII-A. 28428079 9 40 theme crystals 1395:1402 arg1 growth 1370:1375 the growth 1366:1375 the growth of hydroxyapatite crystals in solution 1366:1414 These OPN polymers inhibited the growth of hydroxyapatite crystals in solution at concentrations similar to monomeric OPN, although the crosslinking slightly reduced its inhibitory potency. 28428079 0 41 theme polymeric 66:74 arg1 osteopontin 76:86 transglutaminase-crosslinked polymeric osteopontin 37:86 transglutaminase-crosslinked polymeric osteopontin 37:86 Mineralization-inhibiting effects of transglutaminase-crosslinked polymeric osteopontin. 28428079 5 42 contain has 698:700 arg1 OPN 694:696 Polymeric OPN 684:696 Polymeric OPN 684:696 Polymeric OPN has increased binding to collagen and promotes osteoblast adhesion, but despite these initial observations, its role in mineralization is not clear. 28428079 5 42 contain has 698:700 arg2 binding 712:718 increased binding 702:718 increased binding to collagen 702:730 Polymeric OPN has increased binding to collagen and promotes osteoblast adhesion, but despite these initial observations, its role in mineralization is not clear. 28428079 10 43 theme exogenous 1576:1584 arg1 OPN 1596:1598 this exogenous polymeric OPN 1571:1598 this exogenous polymeric OPN 1571:1598 When added to MC3T3-E1 osteoblast cultures, this exogenous polymeric OPN essentially did not inhibit mineralization when given during the later mineralization stages of culture; however, cultures treated early and then continuously with polymeric OPN throughout both the matrix assembly and mineral deposition stages showed reduced mineralization. 28428079 3 44 theme transglutaminase-mediated 484:508 arg1 crosslinking 510:521 transglutaminase-mediated crosslinking 484:521 transglutaminase-mediated crosslinking of glutamine and lysine residues 484:554 In bone, OPN exists both as a monomer and as a high-molecular-weight polymer - the latter is formed by transglutaminase-mediated crosslinking of glutamine and lysine residues in OPN to create homotypic protein assemblies. 28428079 12 45 theme collagen-rich 2264:2276 arg1 matrix 2278:2283 the dense collagen-rich matrix 2254:2283 the dense collagen-rich matrix 2254:2283 These results suggest that in bone, the increased size and branched structure of crosslinked inhibitory polymeric OPN near the mineralization front could hinder it from accessing focal mineralization sites in the dense collagen-rich matrix, suggesting that OPN-crosslinking into polymers may represent a way to fine-tune the inhibitory potency of OPN on bone mineralization. 28428079 11 46 theme treated 1934:1940 arg1 cultures 1942:1949 these continuously treated cultures 1915:1949 these continuously treated cultures 1915:1949 Immunoblotting of protein extracts from these continuously treated cultures revealed exogenous OPN polymers incorporated into mature matrix that had not yet mineralized. 28428079 10 47 theme assembly 1805:1812 arg1 stages 1837:1842 both the matrix assembly and mineral deposition stages 1789:1842 stages 1837:1842 When added to MC3T3-E1 osteoblast cultures, this exogenous polymeric OPN essentially did not inhibit mineralization when given during the later mineralization stages of culture; however, cultures treated early and then continuously with polymeric OPN throughout both the matrix assembly and mineral deposition stages showed reduced mineralization. 28428079 10 48 theme matrix 1798:1803 arg1 assembly 1805:1812 matrix assembly 1798:1812 matrix assembly 1798:1812 When added to MC3T3-E1 osteoblast cultures, this exogenous polymeric OPN essentially did not inhibit mineralization when given during the later mineralization stages of culture; however, cultures treated early and then continuously with polymeric OPN throughout both the matrix assembly and mineral deposition stages showed reduced mineralization. 28428079 11 49 theme OPN 1970:1972 arg1 polymers 1974:1981 exogenous OPN polymers 1960:1981 exogenous OPN polymers incorporated into mature matrix that had not yet mineralized 1960:2042 Immunoblotting of protein extracts from these continuously treated cultures revealed exogenous OPN polymers incorporated into mature matrix that had not yet mineralized. 28428079 12 50 theme crosslinked 2126:2136 arg1 OPN 2159:2161 crosslinked inhibitory polymeric OPN 2126:2161 crosslinked inhibitory polymeric OPN near the mineralization front 2126:2191 These results suggest that in bone, the increased size and branched structure of crosslinked inhibitory polymeric OPN near the mineralization front could hinder it from accessing focal mineralization sites in the dense collagen-rich matrix, suggesting that OPN-crosslinking into polymers may represent a way to fine-tune the inhibitory potency of OPN on bone mineralization. 28428079 0 51 link transglutaminase-crosslinked 37:64 arg1 osteopontin 76:86 transglutaminase-crosslinked polymeric osteopontin 37:86 transglutaminase-crosslinked polymeric osteopontin 37:86 Mineralization-inhibiting effects of transglutaminase-crosslinked polymeric osteopontin. 28428079 6 52 from effect 882:887 arg1 mineralization 911:924 mineralization 911:924 mineralization 911:924 In this study, we investigated the effect of polymerized OPN on mineralization using a hydroxyapatite crystal growth assay and mineralizing MC3T3-E1 osteoblast cultures. 28428079 10 53 theme deposition 1826:1835 arg1 stages 1837:1842 both the matrix assembly and mineral deposition stages 1789:1842 stages 1837:1842 When added to MC3T3-E1 osteoblast cultures, this exogenous polymeric OPN essentially did not inhibit mineralization when given during the later mineralization stages of culture; however, cultures treated early and then continuously with polymeric OPN throughout both the matrix assembly and mineral deposition stages showed reduced mineralization. 28428079 2 54 theme OPN 340:342 arg1 modification 324:335 enzymatic modification 314:335 enzymatic modification of OPN 314:342 OPN is a well-known inhibitor of matrix mineralization, and enzymatic modification of OPN can affect this inhibitory function. 28428079 6 55 theme polymerized 892:902 arg1 OPN 904:906 polymerized OPN 892:906 polymerized OPN 892:906 In this study, we investigated the effect of polymerized OPN on mineralization using a hydroxyapatite crystal growth assay and mineralizing MC3T3-E1 osteoblast cultures. 28428079 2 56 theme inhibitory 360:369 arg1 function 371:378 this inhibitory function 355:378 this inhibitory function 355:378 OPN is a well-known inhibitor of matrix mineralization, and enzymatic modification of OPN can affect this inhibitory function. 28428079 2 57 theme mineralization 294:307 arg1 OPN 254:256 OPN 254:256 OPN 254:256 OPN is a well-known inhibitor of matrix mineralization, and enzymatic modification of OPN can affect this inhibitory function. 28428079 2 57 theme mineralization 294:307 arg1 inhibitor 274:282 a well-known inhibitor 261:282 a well-known inhibitor of matrix mineralization 261:307 OPN is a well-known inhibitor of matrix mineralization, and enzymatic modification of OPN can affect this inhibitory function. 28428079 12 58 from fine-tune 2356:2364 arg1 mineralization 2404:2417 bone mineralization 2399:2417 bone mineralization 2399:2417 These results suggest that in bone, the increased size and branched structure of crosslinked inhibitory polymeric OPN near the mineralization front could hinder it from accessing focal mineralization sites in the dense collagen-rich matrix, suggesting that OPN-crosslinking into polymers may represent a way to fine-tune the inhibitory potency of OPN on bone mineralization. 28428079 11 59 from Immunoblotting 1875:1888 arg1 cultures 1942:1949 these continuously treated cultures 1915:1949 these continuously treated cultures 1915:1949 Immunoblotting of protein extracts from these continuously treated cultures revealed exogenous OPN polymers incorporated into mature matrix that had not yet mineralized. 28428079 12 60 theme mineralization 2230:2243 arg1 sites 2245:2249 focal mineralization sites 2224:2249 focal mineralization sites 2224:2249 These results suggest that in bone, the increased size and branched structure of crosslinked inhibitory polymeric OPN near the mineralization front could hinder it from accessing focal mineralization sites in the dense collagen-rich matrix, suggesting that OPN-crosslinking into polymers may represent a way to fine-tune the inhibitory potency of OPN on bone mineralization. 28428079 10 61 theme later 1665:1669 arg1 stages 1686:1691 the later mineralization stages 1661:1691 the later mineralization stages of culture 1661:1702 When added to MC3T3-E1 osteoblast cultures, this exogenous polymeric OPN essentially did not inhibit mineralization when given during the later mineralization stages of culture; however, cultures treated early and then continuously with polymeric OPN throughout both the matrix assembly and mineral deposition stages showed reduced mineralization. 28428079 3 62 theme protein 583:589 arg1 assemblies 591:600 homotypic protein assemblies 573:600 homotypic protein assemblies 573:600 In bone, OPN exists both as a monomer and as a high-molecular-weight polymer - the latter is formed by transglutaminase-mediated crosslinking of glutamine and lysine residues in OPN to create homotypic protein assemblies. 28428079 1 63 theme matrix 212:217 arg1 proteins 219:226 mineral-binding matrix proteins 196:226 mineral-binding matrix proteins found in bones and teeth 196:251 Osteopontin (OPN) belongs to the SIBLING family (Small, Integrin-Binding LIgand N-linked Glycoproteins) of mineral-binding matrix proteins found in bones and teeth. 28428079 6 64 theme MC3T3-E1 987:994 arg1 cultures 1007:1014 mineralizing MC3T3-E1 osteoblast cultures 974:1014 mineralizing MC3T3-E1 osteoblast cultures 974:1014 In this study, we investigated the effect of polymerized OPN on mineralization using a hydroxyapatite crystal growth assay and mineralizing MC3T3-E1 osteoblast cultures. 28428079 11 65 theme protein 1893:1899 arg1 extracts 1901:1908 protein extracts 1893:1908 protein extracts from these continuously treated cultures 1893:1949 Immunoblotting of protein extracts from these continuously treated cultures revealed exogenous OPN polymers incorporated into mature matrix that had not yet mineralized. 28428079 9 66 theme inhibitory 1507:1516 arg1 potency 1518:1524 its inhibitory potency 1503:1524 its inhibitory potency 1503:1524 These OPN polymers inhibited the growth of hydroxyapatite crystals in solution at concentrations similar to monomeric OPN, although the crosslinking slightly reduced its inhibitory potency. 28428079 8 67 theme force 1201:1205 arg1 microscopy 1207:1216 atomic force microscopy 1194:1216 atomic force microscopy 1194:1216 In cell-free conditions, TG2 was used to crosslink bovine OPN into its polymeric form, and atomic force microscopy and dynamic light scattering revealed variably-sized, large branched aggregates ranging across hundreds of nanometers. 28428079 8 68 theme branched 1278:1285 arg1 aggregates 1287:1296 variably-sized, large branched aggregates 1256:1296 aggregates 1287:1296 In cell-free conditions, TG2 was used to crosslink bovine OPN into its polymeric form, and atomic force microscopy and dynamic light scattering revealed variably-sized, large branched aggregates ranging across hundreds of nanometers. 28428079 10 69 theme culture 1696:1702 arg1 stages 1686:1691 the later mineralization stages 1661:1691 the later mineralization stages of culture 1661:1702 When added to MC3T3-E1 osteoblast cultures, this exogenous polymeric OPN essentially did not inhibit mineralization when given during the later mineralization stages of culture; however, cultures treated early and then continuously with polymeric OPN throughout both the matrix assembly and mineral deposition stages showed reduced mineralization. 28428079 10 70 theme polymeric 1764:1772 arg1 OPN 1774:1776 polymeric OPN 1764:1776 polymeric OPN throughout both the matrix assembly and mineral deposition stages 1764:1842 When added to MC3T3-E1 osteoblast cultures, this exogenous polymeric OPN essentially did not inhibit mineralization when given during the later mineralization stages of culture; however, cultures treated early and then continuously with polymeric OPN throughout both the matrix assembly and mineral deposition stages showed reduced mineralization. 28428079 6 71 theme growth 957:962 arg1 assay 964:968 a hydroxyapatite crystal growth assay 932:968 a hydroxyapatite crystal growth assay 932:968 In this study, we investigated the effect of polymerized OPN on mineralization using a hydroxyapatite crystal growth assay and mineralizing MC3T3-E1 osteoblast cultures. 28428079 5 72 theme Polymeric 684:692 arg1 OPN 694:696 Polymeric OPN 684:696 Polymeric OPN 684:696 Polymeric OPN has increased binding to collagen and promotes osteoblast adhesion, but despite these initial observations, its role in mineralization is not clear. 28428079 7 73 theme endogenous 1034:1043 arg1 OPN 1055:1057 endogenous polymeric OPN 1034:1057 endogenous polymeric OPN 1034:1057 In the cultures, endogenous polymeric OPN was detected after mineralization occurred. 28428079 8 74 theme light 1230:1234 arg1 scattering 1236:1245 dynamic light scattering 1222:1245 dynamic light scattering 1222:1245 In cell-free conditions, TG2 was used to crosslink bovine OPN into its polymeric form, and atomic force microscopy and dynamic light scattering revealed variably-sized, large branched aggregates ranging across hundreds of nanometers. 28428079 6 75 theme hydroxyapatite 934:947 arg1 assay 964:968 a hydroxyapatite crystal growth assay 932:968 a hydroxyapatite crystal growth assay 932:968 In this study, we investigated the effect of polymerized OPN on mineralization using a hydroxyapatite crystal growth assay and mineralizing MC3T3-E1 osteoblast cultures. 28428079 12 76 theme mineralization 2172:2185 arg1 front 2187:2191 the mineralization front 2168:2191 the mineralization front 2168:2191 These results suggest that in bone, the increased size and branched structure of crosslinked inhibitory polymeric OPN near the mineralization front could hinder it from accessing focal mineralization sites in the dense collagen-rich matrix, suggesting that OPN-crosslinking into polymers may represent a way to fine-tune the inhibitory potency of OPN on bone mineralization. 28428079 7 77 theme polymeric 1045:1053 arg1 OPN 1055:1057 endogenous polymeric OPN 1034:1057 endogenous polymeric OPN 1034:1057 In the cultures, endogenous polymeric OPN was detected after mineralization occurred. 28428079 1 78 located found 228:232 arg2 proteins 219:226 mineral-binding matrix proteins 196:226 mineral-binding matrix proteins found in bones and teeth 196:251 Osteopontin (OPN) belongs to the SIBLING family (Small, Integrin-Binding LIgand N-linked Glycoproteins) of mineral-binding matrix proteins found in bones and teeth. 28428079 1 78 located found 228:232 arg1 teeth 247:251 teeth 247:251 teeth 247:251 Osteopontin (OPN) belongs to the SIBLING family (Small, Integrin-Binding LIgand N-linked Glycoproteins) of mineral-binding matrix proteins found in bones and teeth. 28428079 1 78 located found 228:232 arg1 bones 237:241 bones 237:241 bones 237:241 Osteopontin (OPN) belongs to the SIBLING family (Small, Integrin-Binding LIgand N-linked Glycoproteins) of mineral-binding matrix proteins found in bones and teeth. 28428079 8 79 theme nanometers 1325:1334 arg1 hundreds 1313:1320 hundreds 1313:1320 hundreds of nanometers 1313:1334 In cell-free conditions, TG2 was used to crosslink bovine OPN into its polymeric form, and atomic force microscopy and dynamic light scattering revealed variably-sized, large branched aggregates ranging across hundreds of nanometers. 28428079 2 80 theme well-known 263:272 arg1 OPN 254:256 OPN 254:256 OPN 254:256 OPN is a well-known inhibitor of matrix mineralization, and enzymatic modification of OPN can affect this inhibitory function. 28428079 2 80 theme well-known 263:272 arg1 inhibitor 274:282 a well-known inhibitor 261:282 a well-known inhibitor of matrix mineralization 261:307 OPN is a well-known inhibitor of matrix mineralization, and enzymatic modification of OPN can affect this inhibitory function. 28428079 3 81 dep create 566:571 arg1 OPN 559:561 OPN 559:561 OPN 559:561 In bone, OPN exists both as a monomer and as a high-molecular-weight polymer - the latter is formed by transglutaminase-mediated crosslinking of glutamine and lysine residues in OPN to create homotypic protein assemblies. 28428079 12 82 theme bone 2399:2402 arg1 mineralization 2404:2417 bone mineralization 2399:2417 bone mineralization 2399:2417 These results suggest that in bone, the increased size and branched structure of crosslinked inhibitory polymeric OPN near the mineralization front could hinder it from accessing focal mineralization sites in the dense collagen-rich matrix, suggesting that OPN-crosslinking into polymers may represent a way to fine-tune the inhibitory potency of OPN on bone mineralization. 28428079 12 83 theme polymeric 2149:2157 arg1 OPN 2159:2161 crosslinked inhibitory polymeric OPN 2126:2161 crosslinked inhibitory polymeric OPN near the mineralization front 2126:2191 These results suggest that in bone, the increased size and branched structure of crosslinked inhibitory polymeric OPN near the mineralization front could hinder it from accessing focal mineralization sites in the dense collagen-rich matrix, suggesting that OPN-crosslinking into polymers may represent a way to fine-tune the inhibitory potency of OPN on bone mineralization. 28428079 5 84 from role 810:813 arg1 mineralization 818:831 mineralization 818:831 mineralization 818:831 Polymeric OPN has increased binding to collagen and promotes osteoblast adhesion, but despite these initial observations, its role in mineralization is not clear. 28428079 12 85 link crosslinked 2126:2136 arg1 OPN 2159:2161 crosslinked inhibitory polymeric OPN 2126:2161 crosslinked inhibitory polymeric OPN near the mineralization front 2126:2191 These results suggest that in bone, the increased size and branched structure of crosslinked inhibitory polymeric OPN near the mineralization front could hinder it from accessing focal mineralization sites in the dense collagen-rich matrix, suggesting that OPN-crosslinking into polymers may represent a way to fine-tune the inhibitory potency of OPN on bone mineralization. 28428079 2 86 theme enzymatic 314:322 arg1 modification 324:335 enzymatic modification 314:335 enzymatic modification of OPN 314:342 OPN is a well-known inhibitor of matrix mineralization, and enzymatic modification of OPN can affect this inhibitory function. 28428079 7 87 located detected 1063:1070 arg1 cultures 1024:1031 the cultures 1020:1031 the cultures 1020:1031 In the cultures, endogenous polymeric OPN was detected after mineralization occurred. 28428079 7 87 located detected 1063:1070 arg2 OPN 1055:1057 endogenous polymeric OPN 1034:1057 endogenous polymeric OPN 1034:1057 In the cultures, endogenous polymeric OPN was detected after mineralization occurred. 28428079 9 88 theme OPN 1343:1345 arg1 polymers 1347:1354 These OPN polymers 1337:1354 These OPN polymers 1337:1354 These OPN polymers inhibited the growth of hydroxyapatite crystals in solution at concentrations similar to monomeric OPN, although the crosslinking slightly reduced its inhibitory potency. 28428079 12 89 theme OPN 2392:2394 arg1 potency 2381:2387 the inhibitory potency 2366:2387 the inhibitory potency of OPN 2366:2394 These results suggest that in bone, the increased size and branched structure of crosslinked inhibitory polymeric OPN near the mineralization front could hinder it from accessing focal mineralization sites in the dense collagen-rich matrix, suggesting that OPN-crosslinking into polymers may represent a way to fine-tune the inhibitory potency of OPN on bone mineralization. 28428079 1 90 dep Small 138:142 arg1 Integrin-Binding 145:160 Integrin-Binding 145:160 Integrin-Binding 145:160 Osteopontin (OPN) belongs to the SIBLING family (Small, Integrin-Binding LIgand N-linked Glycoproteins) of mineral-binding matrix proteins found in bones and teeth. 28428079 0 91 theme transglutaminase-crosslinked 37:64 arg1 osteopontin 76:86 transglutaminase-crosslinked polymeric osteopontin 37:86 transglutaminase-crosslinked polymeric osteopontin 37:86 Mineralization-inhibiting effects of transglutaminase-crosslinked polymeric osteopontin. 28428079 8 92 theme cell-free 1106:1114 arg1 conditions 1116:1125 cell-free conditions 1106:1125 cell-free conditions 1106:1125 In cell-free conditions, TG2 was used to crosslink bovine OPN into its polymeric form, and atomic force microscopy and dynamic light scattering revealed variably-sized, large branched aggregates ranging across hundreds of nanometers. 28428079 1 93 theme SIBLING 122:128 arg1 Glycoproteins 178:190 Small, Integrin-Binding LIgand N-linked Glycoproteins 138:190 Small, Integrin-Binding LIgand N-linked Glycoproteins 138:190 Osteopontin (OPN) belongs to the SIBLING family (Small, Integrin-Binding LIgand N-linked Glycoproteins) of mineral-binding matrix proteins found in bones and teeth. 28428079 1 93 theme SIBLING 122:128 arg1 family 130:135 the SIBLING family 118:135 the SIBLING family (Small, Integrin-Binding LIgand N-linked Glycoproteins) of mineral-binding matrix proteins found in bones and teeth 118:251 Osteopontin (OPN) belongs to the SIBLING family (Small, Integrin-Binding LIgand N-linked Glycoproteins) of mineral-binding matrix proteins found in bones and teeth. 28428079 10 94 theme MC3T3-E1 1541:1548 arg1 cultures 1561:1568 MC3T3-E1 osteoblast cultures 1541:1568 MC3T3-E1 osteoblast cultures 1541:1568 When added to MC3T3-E1 osteoblast cultures, this exogenous polymeric OPN essentially did not inhibit mineralization when given during the later mineralization stages of culture; however, cultures treated early and then continuously with polymeric OPN throughout both the matrix assembly and mineral deposition stages showed reduced mineralization. 28428079 0 95 theme osteopontin 76:86 arg1 effects 26:32 Mineralization-inhibiting effects 0:32 Mineralization-inhibiting effects of transglutaminase-crosslinked polymeric osteopontin 0:86 Mineralization-inhibiting effects of transglutaminase-crosslinked polymeric osteopontin. 28428079 9 96 theme hydroxyapatite 1380:1393 arg1 crystals 1395:1402 hydroxyapatite crystals 1380:1402 hydroxyapatite crystals 1380:1402 These OPN polymers inhibited the growth of hydroxyapatite crystals in solution at concentrations similar to monomeric OPN, although the crosslinking slightly reduced its inhibitory potency. 28428079 1 97 link N-linked 169:176 arg1 Glycoproteins 178:190 Small, Integrin-Binding LIgand N-linked Glycoproteins 138:190 Small, Integrin-Binding LIgand N-linked Glycoproteins 138:190 Osteopontin (OPN) belongs to the SIBLING family (Small, Integrin-Binding LIgand N-linked Glycoproteins) of mineral-binding matrix proteins found in bones and teeth. 28428079 1 97 link N-linked 169:176 arg1 family 130:135 the SIBLING family 118:135 the SIBLING family (Small, Integrin-Binding LIgand N-linked Glycoproteins) of mineral-binding matrix proteins found in bones and teeth 118:251 Osteopontin (OPN) belongs to the SIBLING family (Small, Integrin-Binding LIgand N-linked Glycoproteins) of mineral-binding matrix proteins found in bones and teeth. 28428079 11 98 theme exogenous 1960:1968 arg1 polymers 1974:1981 exogenous OPN polymers 1960:1981 exogenous OPN polymers incorporated into mature matrix that had not yet mineralized 1960:2042 Immunoblotting of protein extracts from these continuously treated cultures revealed exogenous OPN polymers incorporated into mature matrix that had not yet mineralized. 28428079 12 99 theme dense 2258:2262 arg1 matrix 2278:2283 the dense collagen-rich matrix 2254:2283 the dense collagen-rich matrix 2254:2283 These results suggest that in bone, the increased size and branched structure of crosslinked inhibitory polymeric OPN near the mineralization front could hinder it from accessing focal mineralization sites in the dense collagen-rich matrix, suggesting that OPN-crosslinking into polymers may represent a way to fine-tune the inhibitory potency of OPN on bone mineralization. 28428079 9 100 theme similar 1434:1440 arg1 concentrations 1419:1432 concentrations 1419:1432 concentrations similar to monomeric OPN 1419:1457 These OPN polymers inhibited the growth of hydroxyapatite crystals in solution at concentrations similar to monomeric OPN, although the crosslinking slightly reduced its inhibitory potency. 28428079 8 101 theme bovine 1154:1159 arg1 OPN 1161:1163 bovine OPN 1154:1163 bovine OPN 1154:1163 In cell-free conditions, TG2 was used to crosslink bovine OPN into its polymeric form, and atomic force microscopy and dynamic light scattering revealed variably-sized, large branched aggregates ranging across hundreds of nanometers. 28428079 3 102 theme lysine 540:545 arg1 residues 547:554 glutamine and lysine residues 526:554 residues 547:554 In bone, OPN exists both as a monomer and as a high-molecular-weight polymer - the latter is formed by transglutaminase-mediated crosslinking of glutamine and lysine residues in OPN to create homotypic protein assemblies. 28428079 9 103 theme monomeric 1445:1453 arg1 OPN 1455:1457 monomeric OPN 1445:1457 monomeric OPN 1445:1457 These OPN polymers inhibited the growth of hydroxyapatite crystals in solution at concentrations similar to monomeric OPN, although the crosslinking slightly reduced its inhibitory potency. 27032077 10 0 theme trap 1743:1746 arg1 spectrometry 1753:1764 ion trap mass spectrometry 1739:1764 ion trap mass spectrometry 1739:1764 The product ion spectra of this Gluc conjugate acquired by ion trap mass spectrometry revealed that the Gluc moiety was linked to the oxygen atom of HONH-PhIP and not the N3 imidazole atom of the oxime tautomer of HONH-PhIP as was originally proposed. 27032077 7 1 theme -Gluc 1272:1276 arg1 formation 1278:1286 AαC-HON(2)-Gluc formation 1262:1286 AαC-HON(2)-Gluc formation 1262:1286 In contrast, AαC-HON(2)-Gluc formation was less affected and other UGT contribute to N(2)-glucuronidation of HONH-AαC. 27032077 10 2 theme HONH-PhIP 1894:1902 arg1 tautomer 1882:1889 the oxime tautomer 1872:1889 the oxime tautomer of HONH-PhIP 1872:1902 The product ion spectra of this Gluc conjugate acquired by ion trap mass spectrometry revealed that the Gluc moiety was linked to the oxygen atom of HONH-PhIP and not the N3 imidazole atom of the oxime tautomer of HONH-PhIP as was originally proposed. 27032077 5 3 dep -Gluc 951:955 arg1 2 949:949 2 949:949 2 949:949 We measured the rates of formation of AαC-HON(2)-Gluc and AαC-HN(2)-O-Gluc in human organs: highest activity occurred with liver and kidney microsomes, and lesser activity was found with colon and rectum microsomes. 27032077 5 4 theme colon 1090:1094 arg1 microsomes 1107:1116 colon and rectum microsomes 1090:1116 colon and rectum microsomes 1090:1116 We measured the rates of formation of AαC-HON(2)-Gluc and AαC-HN(2)-O-Gluc in human organs: highest activity occurred with liver and kidney microsomes, and lesser activity was found with colon and rectum microsomes. 27032077 8 5 theme genotoxic 1540:1548 arg1 pyridine 1514:1521 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine 1468:1521 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine (HONH-PhIP) 1468:1533 UGT were reported to catalyze the formation of isomeric Gluc conjugates at the N(2) and N3 atoms of 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine (HONH-PhIP), the genotoxic metabolite of PhIP. 27032077 8 5 theme genotoxic 1540:1548 arg1 metabolite 1550:1559 the genotoxic metabolite 1536:1559 the genotoxic metabolite of PhIP 1536:1567 UGT were reported to catalyze the formation of isomeric Gluc conjugates at the N(2) and N3 atoms of 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine (HONH-PhIP), the genotoxic metabolite of PhIP. 27032077 1 6 theme aromatic 205:212 arg1 amines 214:219 carcinogenic heterocyclic aromatic amines 179:219 carcinogenic heterocyclic aromatic amines (HAA) that arise during the burning of tobacco and cooking of meats 179:287 2-Amino-9H-pyrido[2,3-b]indole (AαC) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are carcinogenic heterocyclic aromatic amines (HAA) that arise during the burning of tobacco and cooking of meats. 27032077 1 6 theme aromatic 205:212 arg1 AαC 111:113 2-Amino-9H-pyrido[2,3-b]indole (AαC) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine 79:166 AαC 111:113 2-Amino-9H-pyrido[2,3-b]indole (AαC) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are carcinogenic heterocyclic aromatic amines (HAA) that arise during the burning of tobacco and cooking of meats. 27032077 1 6 theme aromatic 205:212 arg1 pyridine 159:166 2-Amino-9H-pyrido[2,3-b]indole (AαC) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine 79:166 pyridine 159:166 2-Amino-9H-pyrido[2,3-b]indole (AαC) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are carcinogenic heterocyclic aromatic amines (HAA) that arise during the burning of tobacco and cooking of meats. 27032077 1 6 theme aromatic 205:212 arg1 HAA 222:224 HAA 222:224 HAA 222:224 2-Amino-9H-pyrido[2,3-b]indole (AαC) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are carcinogenic heterocyclic aromatic amines (HAA) that arise during the burning of tobacco and cooking of meats. 27032077 7 7 from affected 1297:1304 arg1 contrast 1252:1259 contrast 1252:1259 contrast 1252:1259 In contrast, AαC-HON(2)-Gluc formation was less affected and other UGT contribute to N(2)-glucuronidation of HONH-AαC. 27032077 10 8 theme tautomer 1882:1889 arg1 atom 1864:1867 not the N3 imidazole atom 1843:1867 not the N3 imidazole atom of the oxime tautomer of HONH-PhIP 1843:1902 The product ion spectra of this Gluc conjugate acquired by ion trap mass spectrometry revealed that the Gluc moiety was linked to the oxygen atom of HONH-PhIP and not the N3 imidazole atom of the oxime tautomer of HONH-PhIP as was originally proposed. 27032077 10 8 theme tautomer 1882:1889 arg1 atom 1821:1824 the oxygen atom 1810:1824 the oxygen atom of HONH-PhIP 1810:1837 The product ion spectra of this Gluc conjugate acquired by ion trap mass spectrometry revealed that the Gluc moiety was linked to the oxygen atom of HONH-PhIP and not the N3 imidazole atom of the oxime tautomer of HONH-PhIP as was originally proposed. 27032077 10 9 attach linked 1800:1805 arg2 moiety 1789:1794 the Gluc moiety 1780:1794 the Gluc moiety 1780:1794 The product ion spectra of this Gluc conjugate acquired by ion trap mass spectrometry revealed that the Gluc moiety was linked to the oxygen atom of HONH-PhIP and not the N3 imidazole atom of the oxime tautomer of HONH-PhIP as was originally proposed. 27032077 10 9 attach linked 1800:1805 arg1 atom 1821:1824 the oxygen atom 1810:1824 the oxygen atom of HONH-PhIP 1810:1837 The product ion spectra of this Gluc conjugate acquired by ion trap mass spectrometry revealed that the Gluc moiety was linked to the oxygen atom of HONH-PhIP and not the N3 imidazole atom of the oxime tautomer of HONH-PhIP as was originally proposed. 27032077 10 9 attach linked 1800:1805 arg1 atom 1864:1867 not the N3 imidazole atom 1843:1867 not the N3 imidazole atom of the oxime tautomer of HONH-PhIP 1843:1902 The product ion spectra of this Gluc conjugate acquired by ion trap mass spectrometry revealed that the Gluc moiety was linked to the oxygen atom of HONH-PhIP and not the N3 imidazole atom of the oxime tautomer of HONH-PhIP as was originally proposed. 27032077 7 10 theme AαC-HON 1262:1268 arg1 formation 1278:1286 AαC-HON(2)-Gluc formation 1262:1286 AαC-HON(2)-Gluc formation 1262:1286 In contrast, AαC-HON(2)-Gluc formation was less affected and other UGT contribute to N(2)-glucuronidation of HONH-AαC. 27032077 5 11 theme -O-Gluc 970:976 arg1 formation 928:936 formation 928:936 formation of AαC-HON(2)-Gluc and AαC-HN(2)-O-Gluc 928:976 We measured the rates of formation of AαC-HON(2)-Gluc and AαC-HN(2)-O-Gluc in human organs: highest activity occurred with liver and kidney microsomes, and lesser activity was found with colon and rectum microsomes. 27032077 12 12 theme bioactivation 2221:2233 arg1 O-glucuronidation 2147:2163 The regioselective O-glucuronidation 2128:2163 The regioselective O-glucuronidation 2128:2163 The regioselective O-glucuronidation of HONH-AαC and HONH-PhIP, by UGT1A9, is a mechanism of bioactivation of these ubiquitous HAAs. 27032077 12 12 theme bioactivation 2221:2233 arg1 mechanism 2208:2216 a mechanism 2206:2216 a mechanism of bioactivation of these ubiquitous HAAs 2206:2258 The regioselective O-glucuronidation of HONH-AαC and HONH-PhIP, by UGT1A9, is a mechanism of bioactivation of these ubiquitous HAAs. 27032077 5 13 theme human 981:985 arg1 organs 987:992 human organs 981:992 human organs 981:992 We measured the rates of formation of AαC-HON(2)-Gluc and AαC-HN(2)-O-Gluc in human organs: highest activity occurred with liver and kidney microsomes, and lesser activity was found with colon and rectum microsomes. 27032077 6 14 theme AαC-HN 1119:1124 arg1 formation 1136:1144 AαC-HN(2)-O-Gluc formation 1119:1144 AαC-HN(2)-O-Gluc formation 1119:1144 AαC-HN(2)-O-Gluc formation was largely diminished in liver and kidney microsomes, by niflumic acid, a selective inhibitor UGT1A9. 27032077 10 15 theme Gluc 1784:1787 arg1 moiety 1789:1794 the Gluc moiety 1780:1794 the Gluc moiety 1780:1794 The product ion spectra of this Gluc conjugate acquired by ion trap mass spectrometry revealed that the Gluc moiety was linked to the oxygen atom of HONH-PhIP and not the N3 imidazole atom of the oxime tautomer of HONH-PhIP as was originally proposed. 27032077 5 16 theme AαC-HN 961:966 arg1 -O-Gluc 970:976 AαC-HN(2)-O-Gluc 961:976 AαC-HN(2)-O-Gluc 961:976 We measured the rates of formation of AαC-HON(2)-Gluc and AαC-HN(2)-O-Gluc in human organs: highest activity occurred with liver and kidney microsomes, and lesser activity was found with colon and rectum microsomes. 27032077 10 17 theme oxygen 1814:1819 arg1 atom 1821:1824 the oxygen atom 1810:1824 the oxygen atom of HONH-PhIP 1810:1837 The product ion spectra of this Gluc conjugate acquired by ion trap mass spectrometry revealed that the Gluc moiety was linked to the oxygen atom of HONH-PhIP and not the N3 imidazole atom of the oxime tautomer of HONH-PhIP as was originally proposed. 27032077 5 18 theme rectum 1100:1105 arg1 microsomes 1107:1116 colon and rectum microsomes 1090:1116 colon and rectum microsomes 1090:1116 We measured the rates of formation of AαC-HON(2)-Gluc and AαC-HN(2)-O-Gluc in human organs: highest activity occurred with liver and kidney microsomes, and lesser activity was found with colon and rectum microsomes. 27032077 11 19 theme human 1977:1981 arg1 liver 1983:1987 human liver 1977:1987 human liver 1977:1987 UGT1A9, an abundant UGT isoform expressed in human liver and kidney, preferentially forms the O-linked Gluc conjugates of HONH-AαC and HONH-PhIP as opposed to their detoxicated N(2)-Gluc isomers. 27032077 11 20 link O-linked 2026:2033 arg1 conjugates 2040:2049 the O-linked Gluc conjugates 2022:2049 the O-linked Gluc conjugates of HONH-AαC and HONH-PhIP 2022:2075 UGT1A9, an abundant UGT isoform expressed in human liver and kidney, preferentially forms the O-linked Gluc conjugates of HONH-AαC and HONH-PhIP as opposed to their detoxicated N(2)-Gluc isomers. 27032077 1 21 theme carcinogenic 179:190 arg1 amines 214:219 carcinogenic heterocyclic aromatic amines 179:219 carcinogenic heterocyclic aromatic amines (HAA) that arise during the burning of tobacco and cooking of meats 179:287 2-Amino-9H-pyrido[2,3-b]indole (AαC) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are carcinogenic heterocyclic aromatic amines (HAA) that arise during the burning of tobacco and cooking of meats. 27032077 1 21 theme carcinogenic 179:190 arg1 AαC 111:113 2-Amino-9H-pyrido[2,3-b]indole (AαC) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine 79:166 AαC 111:113 2-Amino-9H-pyrido[2,3-b]indole (AαC) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are carcinogenic heterocyclic aromatic amines (HAA) that arise during the burning of tobacco and cooking of meats. 27032077 1 21 theme carcinogenic 179:190 arg1 pyridine 159:166 2-Amino-9H-pyrido[2,3-b]indole (AαC) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine 79:166 pyridine 159:166 2-Amino-9H-pyrido[2,3-b]indole (AαC) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are carcinogenic heterocyclic aromatic amines (HAA) that arise during the burning of tobacco and cooking of meats. 27032077 1 21 theme carcinogenic 179:190 arg1 HAA 222:224 HAA 222:224 HAA 222:224 2-Amino-9H-pyrido[2,3-b]indole (AαC) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are carcinogenic heterocyclic aromatic amines (HAA) that arise during the burning of tobacco and cooking of meats. 27032077 3 22 theme genotoxic 383:391 arg1 metabolite 408:417 The genotoxic N-hydroxylated metabolite 379:417 The genotoxic N-hydroxylated metabolite 379:417 The genotoxic N-hydroxylated metabolite of AαC, 2-hydroxyamino-9H-pyrido[2,3-b]indole (HONH-AαC), undergoes glucuronidation to form the isomeric glucuronide (Gluc) conjugates N(2)-(β-d-glucosidurony1)-2-hydroxyamino-9H-pyrido[2,3-b]indole (AαC-HON(2)-Gluc) and O-(β-d-glucosidurony1)-2-hydroxyamino-9H-pyrido[2,3-b]indole (AαC-HN(2)-O-Gluc). 27032077 8 23 dep N 1447:1447 arg1 the 1443:1445 the 1443:1445 the 1443:1445 UGT were reported to catalyze the formation of isomeric Gluc conjugates at the N(2) and N3 atoms of 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine (HONH-PhIP), the genotoxic metabolite of PhIP. 27032077 1 24 theme 2-Amino-9H-pyrido[2,3-b 79:101 arg1 amines 214:219 carcinogenic heterocyclic aromatic amines 179:219 carcinogenic heterocyclic aromatic amines (HAA) that arise during the burning of tobacco and cooking of meats 179:287 2-Amino-9H-pyrido[2,3-b]indole (AαC) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are carcinogenic heterocyclic aromatic amines (HAA) that arise during the burning of tobacco and cooking of meats. 27032077 1 24 theme 2-Amino-9H-pyrido[2,3-b 79:101 arg1 AαC 111:113 2-Amino-9H-pyrido[2,3-b]indole (AαC) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine 79:166 AαC 111:113 2-Amino-9H-pyrido[2,3-b]indole (AαC) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are carcinogenic heterocyclic aromatic amines (HAA) that arise during the burning of tobacco and cooking of meats. 27032077 1 24 theme 2-Amino-9H-pyrido[2,3-b 79:101 arg1 pyridine 159:166 2-Amino-9H-pyrido[2,3-b]indole (AαC) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine 79:166 pyridine 159:166 2-Amino-9H-pyrido[2,3-b]indole (AαC) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are carcinogenic heterocyclic aromatic amines (HAA) that arise during the burning of tobacco and cooking of meats. 27032077 1 24 theme 2-Amino-9H-pyrido[2,3-b 79:101 arg1 PhIP 169:172 PhIP 169:172 PhIP 169:172 2-Amino-9H-pyrido[2,3-b]indole (AαC) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are carcinogenic heterocyclic aromatic amines (HAA) that arise during the burning of tobacco and cooking of meats. 27032077 4 25 theme stable 742:747 arg1 metabolite 749:758 a stable metabolite 740:758 a stable metabolite 740:758 AαC-HON(2)-Gluc is a stable metabolite but AαC-HN(2)-O-Gluc is a biologically reactive intermediate, which covalently adducts to DNA at levels that are 20-fold higher than HONH-AαC. 27032077 4 25 theme stable 742:747 arg1 -Gluc 731:735 AαC-HON(2)-Gluc 721:735 AαC-HON(2)-Gluc 721:735 AαC-HON(2)-Gluc is a stable metabolite but AαC-HN(2)-O-Gluc is a biologically reactive intermediate, which covalently adducts to DNA at levels that are 20-fold higher than HONH-AαC. 27032077 1 26 theme indole 103:108 arg1 amines 214:219 carcinogenic heterocyclic aromatic amines 179:219 carcinogenic heterocyclic aromatic amines (HAA) that arise during the burning of tobacco and cooking of meats 179:287 2-Amino-9H-pyrido[2,3-b]indole (AαC) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are carcinogenic heterocyclic aromatic amines (HAA) that arise during the burning of tobacco and cooking of meats. 27032077 1 26 theme indole 103:108 arg1 AαC 111:113 2-Amino-9H-pyrido[2,3-b]indole (AαC) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine 79:166 AαC 111:113 2-Amino-9H-pyrido[2,3-b]indole (AαC) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are carcinogenic heterocyclic aromatic amines (HAA) that arise during the burning of tobacco and cooking of meats. 27032077 1 26 theme indole 103:108 arg1 pyridine 159:166 2-Amino-9H-pyrido[2,3-b]indole (AαC) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine 79:166 pyridine 159:166 2-Amino-9H-pyrido[2,3-b]indole (AαC) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are carcinogenic heterocyclic aromatic amines (HAA) that arise during the burning of tobacco and cooking of meats. 27032077 1 26 theme indole 103:108 arg1 PhIP 169:172 PhIP 169:172 PhIP 169:172 2-Amino-9H-pyrido[2,3-b]indole (AαC) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are carcinogenic heterocyclic aromatic amines (HAA) that arise during the burning of tobacco and cooking of meats. 27032077 9 27 theme HONH-PhIP 1608:1616 arg1 N3-Gluc 1597:1603 the N3-Gluc 1593:1603 the N3-Gluc of HONH-PhIP 1593:1616 However, we found that the N3-Gluc of HONH-PhIP also covalently bound to DNA at higher levels than HONH-PhIP. 27032077 3 28 dep indole 458:463 arg1 2-hydroxyamino-9H-pyrido[2,3-b 427:456 AαC, 2-hydroxyamino-9H-pyrido[2,3-b]indole 422:463 2-hydroxyamino-9H-pyrido[2,3-b 427:456 The genotoxic N-hydroxylated metabolite of AαC, 2-hydroxyamino-9H-pyrido[2,3-b]indole (HONH-AαC), undergoes glucuronidation to form the isomeric glucuronide (Gluc) conjugates N(2)-(β-d-glucosidurony1)-2-hydroxyamino-9H-pyrido[2,3-b]indole (AαC-HON(2)-Gluc) and O-(β-d-glucosidurony1)-2-hydroxyamino-9H-pyrido[2,3-b]indole (AαC-HN(2)-O-Gluc). 27032077 1 29 theme meats 283:287 arg1 cooking 272:278 cooking 272:278 cooking 272:278 2-Amino-9H-pyrido[2,3-b]indole (AαC) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are carcinogenic heterocyclic aromatic amines (HAA) that arise during the burning of tobacco and cooking of meats. 27032077 1 29 theme meats 283:287 arg1 tobacco 260:266 tobacco 260:266 tobacco 260:266 2-Amino-9H-pyrido[2,3-b]indole (AαC) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are carcinogenic heterocyclic aromatic amines (HAA) that arise during the burning of tobacco and cooking of meats. 27032077 0 30 theme Heterocyclic 17:28 arg1 Amines 39:44 Heterocyclic Aromatic Amines 17:44 Heterocyclic Aromatic Amines 17:44 Bioactivation of Heterocyclic Aromatic Amines by UDP Glucuronosyltransferases. 27032077 7 31 from contrast 1252:1259 arg1 affected 1297:1304 affected 1297:1304 affected 1297:1304 In contrast, AαC-HON(2)-Gluc formation was less affected and other UGT contribute to N(2)-glucuronidation of HONH-AαC. 27032077 3 32 theme indole 458:463 arg1 metabolite 408:417 The genotoxic N-hydroxylated metabolite 379:417 The genotoxic N-hydroxylated metabolite 379:417 The genotoxic N-hydroxylated metabolite of AαC, 2-hydroxyamino-9H-pyrido[2,3-b]indole (HONH-AαC), undergoes glucuronidation to form the isomeric glucuronide (Gluc) conjugates N(2)-(β-d-glucosidurony1)-2-hydroxyamino-9H-pyrido[2,3-b]indole (AαC-HON(2)-Gluc) and O-(β-d-glucosidurony1)-2-hydroxyamino-9H-pyrido[2,3-b]indole (AαC-HN(2)-O-Gluc). 27032077 3 33 dep indole 611:616 arg1 -O-Gluc 711:717 AαC-HN(2)-O-Gluc 702:717 AαC-HN(2)-O-Gluc 702:717 The genotoxic N-hydroxylated metabolite of AαC, 2-hydroxyamino-9H-pyrido[2,3-b]indole (HONH-AαC), undergoes glucuronidation to form the isomeric glucuronide (Gluc) conjugates N(2)-(β-d-glucosidurony1)-2-hydroxyamino-9H-pyrido[2,3-b]indole (AαC-HON(2)-Gluc) and O-(β-d-glucosidurony1)-2-hydroxyamino-9H-pyrido[2,3-b]indole (AαC-HN(2)-O-Gluc). 27032077 3 33 dep indole 611:616 arg1 N 554:554 N(2)- 554:558 N(2)- 554:558 The genotoxic N-hydroxylated metabolite of AαC, 2-hydroxyamino-9H-pyrido[2,3-b]indole (HONH-AαC), undergoes glucuronidation to form the isomeric glucuronide (Gluc) conjugates N(2)-(β-d-glucosidurony1)-2-hydroxyamino-9H-pyrido[2,3-b]indole (AαC-HON(2)-Gluc) and O-(β-d-glucosidurony1)-2-hydroxyamino-9H-pyrido[2,3-b]indole (AαC-HN(2)-O-Gluc). 27032077 3 33 dep indole 611:616 arg1 -Gluc 629:633 AαC-HON(2)-Gluc 619:633 AαC-HON(2)-Gluc 619:633 The genotoxic N-hydroxylated metabolite of AαC, 2-hydroxyamino-9H-pyrido[2,3-b]indole (HONH-AαC), undergoes glucuronidation to form the isomeric glucuronide (Gluc) conjugates N(2)-(β-d-glucosidurony1)-2-hydroxyamino-9H-pyrido[2,3-b]indole (AαC-HON(2)-Gluc) and O-(β-d-glucosidurony1)-2-hydroxyamino-9H-pyrido[2,3-b]indole (AαC-HN(2)-O-Gluc). 27032077 7 34 dep affected 1297:1304 arg1 contribute 1320:1329 contribute 1320:1329 contribute to N(2)-glucuronidation of HONH-AαC 1320:1365 In contrast, AαC-HON(2)-Gluc formation was less affected and other UGT contribute to N(2)-glucuronidation of HONH-AαC. 27032077 0 35 theme Amines 39:44 arg1 Bioactivation 0:12 Bioactivation 0:12 Bioactivation of Heterocyclic Aromatic Amines by UDP 0:51 Bioactivation of Heterocyclic Aromatic Amines by UDP Glucuronosyltransferases. 27032077 7 36 theme HONH-AαC 1358:1365 arg1 -glucuronidation 1338:1353 N(2)-glucuronidation 1334:1353 N(2)-glucuronidation of HONH-AαC 1334:1365 In contrast, AαC-HON(2)-Gluc formation was less affected and other UGT contribute to N(2)-glucuronidation of HONH-AαC. 27032077 11 37 theme UGT 1952:1954 arg1 isoform 1956:1962 an abundant UGT isoform 1940:1962 an abundant UGT isoform expressed in human liver and kidney 1940:1998 UGT1A9, an abundant UGT isoform expressed in human liver and kidney, preferentially forms the O-linked Gluc conjugates of HONH-AαC and HONH-PhIP as opposed to their detoxicated N(2)-Gluc isomers. 27032077 11 37 theme UGT 1952:1954 arg1 UGT1A9 1932:1937 UGT1A9 1932:1937 UGT1A9 1932:1937 UGT1A9, an abundant UGT isoform expressed in human liver and kidney, preferentially forms the O-linked Gluc conjugates of HONH-AαC and HONH-PhIP as opposed to their detoxicated N(2)-Gluc isomers. 27032077 7 38 dep other 1310:1314 arg1 UGT 1316:1318 UGT 1316:1318 UGT 1316:1318 In contrast, AαC-HON(2)-Gluc formation was less affected and other UGT contribute to N(2)-glucuronidation of HONH-AαC. 27032077 10 39 theme imidazole 1854:1862 arg1 atom 1864:1867 not the N3 imidazole atom 1843:1867 not the N3 imidazole atom of the oxime tautomer of HONH-PhIP 1843:1902 The product ion spectra of this Gluc conjugate acquired by ion trap mass spectrometry revealed that the Gluc moiety was linked to the oxygen atom of HONH-PhIP and not the N3 imidazole atom of the oxime tautomer of HONH-PhIP as was originally proposed. 27032077 8 40 theme isomeric 1415:1422 arg1 conjugates 1429:1438 isomeric Gluc conjugates 1415:1438 isomeric Gluc conjugates 1415:1438 UGT were reported to catalyze the formation of isomeric Gluc conjugates at the N(2) and N3 atoms of 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine (HONH-PhIP), the genotoxic metabolite of PhIP. 27032077 10 41 theme ion 1692:1694 arg1 spectra 1696:1702 The product ion spectra 1680:1702 The product ion spectra of this Gluc conjugate acquired by ion trap mass spectrometry 1680:1764 The product ion spectra of this Gluc conjugate acquired by ion trap mass spectrometry revealed that the Gluc moiety was linked to the oxygen atom of HONH-PhIP and not the N3 imidazole atom of the oxime tautomer of HONH-PhIP as was originally proposed. 27032077 3 42 theme isomeric 515:522 arg1 conjugates 543:552 the isomeric glucuronide (Gluc) conjugates 511:552 the isomeric glucuronide (Gluc) conjugates N(2)-(β-d-glucosidurony1)-2-hydroxyamino-9H-pyrido[2,3-b]indole (AαC-HON(2)-Gluc) and O-(β-d-glucosidurony1)-2-hydroxyamino-9H-pyrido[2,3-b]indole (AαC-HN(2)-O-Gluc) 511:718 The genotoxic N-hydroxylated metabolite of AαC, 2-hydroxyamino-9H-pyrido[2,3-b]indole (HONH-AαC), undergoes glucuronidation to form the isomeric glucuronide (Gluc) conjugates N(2)-(β-d-glucosidurony1)-2-hydroxyamino-9H-pyrido[2,3-b]indole (AαC-HON(2)-Gluc) and O-(β-d-glucosidurony1)-2-hydroxyamino-9H-pyrido[2,3-b]indole (AαC-HN(2)-O-Gluc). 27032077 8 43 theme N3 1456:1457 arg1 atoms 1459:1463 N3 atoms 1456:1463 N3 atoms 1456:1463 UGT were reported to catalyze the formation of isomeric Gluc conjugates at the N(2) and N3 atoms of 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine (HONH-PhIP), the genotoxic metabolite of PhIP. 27032077 8 44 theme conjugates 1429:1438 arg1 formation 1402:1410 the formation 1398:1410 the formation of isomeric Gluc conjugates 1398:1438 UGT were reported to catalyze the formation of isomeric Gluc conjugates at the N(2) and N3 atoms of 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine (HONH-PhIP), the genotoxic metabolite of PhIP. 27032077 7 45 theme N 1334:1334 arg1 -glucuronidation 1338:1353 N(2)-glucuronidation 1334:1353 N(2)-glucuronidation of HONH-AαC 1334:1365 In contrast, AαC-HON(2)-Gluc formation was less affected and other UGT contribute to N(2)-glucuronidation of HONH-AαC. 27032077 10 46 theme oxime 1876:1880 arg1 tautomer 1882:1889 the oxime tautomer 1872:1889 the oxime tautomer of HONH-PhIP 1872:1902 The product ion spectra of this Gluc conjugate acquired by ion trap mass spectrometry revealed that the Gluc moiety was linked to the oxygen atom of HONH-PhIP and not the N3 imidazole atom of the oxime tautomer of HONH-PhIP as was originally proposed. 27032077 10 47 theme Gluc 1712:1715 arg1 conjugate 1717:1725 this Gluc conjugate 1707:1725 this Gluc conjugate 1707:1725 The product ion spectra of this Gluc conjugate acquired by ion trap mass spectrometry revealed that the Gluc moiety was linked to the oxygen atom of HONH-PhIP and not the N3 imidazole atom of the oxime tautomer of HONH-PhIP as was originally proposed. 27032077 6 48 theme liver 1172:1176 arg1 microsomes 1189:1198 liver and kidney microsomes 1172:1198 liver and kidney microsomes 1172:1198 AαC-HN(2)-O-Gluc formation was largely diminished in liver and kidney microsomes, by niflumic acid, a selective inhibitor UGT1A9. 27032077 1 49 theme tobacco 260:266 arg1 burning 249:255 the burning 245:255 the burning of tobacco and cooking of meats 245:287 2-Amino-9H-pyrido[2,3-b]indole (AαC) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are carcinogenic heterocyclic aromatic amines (HAA) that arise during the burning of tobacco and cooking of meats. 27032077 3 50 theme AαC-HN 702:707 arg1 -O-Gluc 711:717 AαC-HN(2)-O-Gluc 702:717 AαC-HN(2)-O-Gluc 702:717 The genotoxic N-hydroxylated metabolite of AαC, 2-hydroxyamino-9H-pyrido[2,3-b]indole (HONH-AαC), undergoes glucuronidation to form the isomeric glucuronide (Gluc) conjugates N(2)-(β-d-glucosidurony1)-2-hydroxyamino-9H-pyrido[2,3-b]indole (AαC-HON(2)-Gluc) and O-(β-d-glucosidurony1)-2-hydroxyamino-9H-pyrido[2,3-b]indole (AαC-HN(2)-O-Gluc). 27032077 1 51 theme cooking 272:278 arg1 burning 249:255 the burning 245:255 the burning of tobacco and cooking of meats 245:287 2-Amino-9H-pyrido[2,3-b]indole (AαC) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are carcinogenic heterocyclic aromatic amines (HAA) that arise during the burning of tobacco and cooking of meats. 27032077 12 52 theme HAAs 2255:2258 arg1 bioactivation 2221:2233 bioactivation 2221:2233 bioactivation of these ubiquitous HAAs 2221:2258 The regioselective O-glucuronidation of HONH-AαC and HONH-PhIP, by UGT1A9, is a mechanism of bioactivation of these ubiquitous HAAs. 27032077 12 53 theme ubiquitous 2244:2253 arg1 HAAs 2255:2258 these ubiquitous HAAs 2238:2258 these ubiquitous HAAs 2238:2258 The regioselective O-glucuronidation of HONH-AαC and HONH-PhIP, by UGT1A9, is a mechanism of bioactivation of these ubiquitous HAAs. 27032077 11 54 theme Gluc 2035:2038 arg1 conjugates 2040:2049 the O-linked Gluc conjugates 2022:2049 the O-linked Gluc conjugates of HONH-AαC and HONH-PhIP 2022:2075 UGT1A9, an abundant UGT isoform expressed in human liver and kidney, preferentially forms the O-linked Gluc conjugates of HONH-AαC and HONH-PhIP as opposed to their detoxicated N(2)-Gluc isomers. 27032077 10 55 theme ion 1739:1741 arg1 spectrometry 1753:1764 ion trap mass spectrometry 1739:1764 ion trap mass spectrometry 1739:1764 The product ion spectra of this Gluc conjugate acquired by ion trap mass spectrometry revealed that the Gluc moiety was linked to the oxygen atom of HONH-PhIP and not the N3 imidazole atom of the oxime tautomer of HONH-PhIP as was originally proposed. 27032077 1 56 theme heterocyclic 192:203 arg1 amines 214:219 carcinogenic heterocyclic aromatic amines 179:219 carcinogenic heterocyclic aromatic amines (HAA) that arise during the burning of tobacco and cooking of meats 179:287 2-Amino-9H-pyrido[2,3-b]indole (AαC) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are carcinogenic heterocyclic aromatic amines (HAA) that arise during the burning of tobacco and cooking of meats. 27032077 1 56 theme heterocyclic 192:203 arg1 AαC 111:113 2-Amino-9H-pyrido[2,3-b]indole (AαC) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine 79:166 AαC 111:113 2-Amino-9H-pyrido[2,3-b]indole (AαC) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are carcinogenic heterocyclic aromatic amines (HAA) that arise during the burning of tobacco and cooking of meats. 27032077 1 56 theme heterocyclic 192:203 arg1 pyridine 159:166 2-Amino-9H-pyrido[2,3-b]indole (AαC) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine 79:166 pyridine 159:166 2-Amino-9H-pyrido[2,3-b]indole (AαC) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are carcinogenic heterocyclic aromatic amines (HAA) that arise during the burning of tobacco and cooking of meats. 27032077 1 56 theme heterocyclic 192:203 arg1 HAA 222:224 HAA 222:224 HAA 222:224 2-Amino-9H-pyrido[2,3-b]indole (AαC) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are carcinogenic heterocyclic aromatic amines (HAA) that arise during the burning of tobacco and cooking of meats. 27032077 11 57 theme O-linked 2026:2033 arg1 conjugates 2040:2049 the O-linked Gluc conjugates 2022:2049 the O-linked Gluc conjugates of HONH-AαC and HONH-PhIP 2022:2075 UGT1A9, an abundant UGT isoform expressed in human liver and kidney, preferentially forms the O-linked Gluc conjugates of HONH-AαC and HONH-PhIP as opposed to their detoxicated N(2)-Gluc isomers. 27032077 6 58 theme -O-Gluc 1128:1134 arg1 formation 1136:1144 AαC-HN(2)-O-Gluc formation 1119:1144 AαC-HN(2)-O-Gluc formation 1119:1144 AαC-HN(2)-O-Gluc formation was largely diminished in liver and kidney microsomes, by niflumic acid, a selective inhibitor UGT1A9. 27032077 2 59 theme many 336:339 arg1 procarcinogens 341:354 many procarcinogens 336:354 many procarcinogens 336:354 UDP-glucuronosyltransferases (UGT) detoxicate many procarcinogens and their metabolites. 27032077 4 60 theme reactive 799:806 arg1 intermediate 808:819 a biologically reactive intermediate 784:819 a biologically reactive intermediate 784:819 AαC-HON(2)-Gluc is a stable metabolite but AαC-HN(2)-O-Gluc is a biologically reactive intermediate, which covalently adducts to DNA at levels that are 20-fold higher than HONH-AαC. 27032077 4 60 theme reactive 799:806 arg1 -O-Gluc 773:779 AαC-HN(2)-O-Gluc 764:779 AαC-HN(2)-O-Gluc 764:779 AαC-HON(2)-Gluc is a stable metabolite but AαC-HN(2)-O-Gluc is a biologically reactive intermediate, which covalently adducts to DNA at levels that are 20-fold higher than HONH-AαC. 27032077 11 61 theme HONH-PhIP 2067:2075 arg1 conjugates 2040:2049 the O-linked Gluc conjugates 2022:2049 the O-linked Gluc conjugates of HONH-AαC and HONH-PhIP 2022:2075 UGT1A9, an abundant UGT isoform expressed in human liver and kidney, preferentially forms the O-linked Gluc conjugates of HONH-AαC and HONH-PhIP as opposed to their detoxicated N(2)-Gluc isomers. 27032077 11 62 theme HONH-AαC 2054:2061 arg1 conjugates 2040:2049 the O-linked Gluc conjugates 2022:2049 the O-linked Gluc conjugates of HONH-AαC and HONH-PhIP 2022:2075 UGT1A9, an abundant UGT isoform expressed in human liver and kidney, preferentially forms the O-linked Gluc conjugates of HONH-AαC and HONH-PhIP as opposed to their detoxicated N(2)-Gluc isomers. 27032077 10 63 theme mass 1748:1751 arg1 spectrometry 1753:1764 ion trap mass spectrometry 1739:1764 ion trap mass spectrometry 1739:1764 The product ion spectra of this Gluc conjugate acquired by ion trap mass spectrometry revealed that the Gluc moiety was linked to the oxygen atom of HONH-PhIP and not the N3 imidazole atom of the oxime tautomer of HONH-PhIP as was originally proposed. 27032077 6 64 theme niflumic 1204:1211 arg1 inhibitor 1231:1239 a selective inhibitor UGT1A9 1219:1246 a selective inhibitor UGT1A9 1219:1246 AαC-HN(2)-O-Gluc formation was largely diminished in liver and kidney microsomes, by niflumic acid, a selective inhibitor UGT1A9. 27032077 6 64 theme niflumic 1204:1211 arg1 acid 1213:1216 niflumic acid 1204:1216 niflumic acid 1204:1216 AαC-HN(2)-O-Gluc formation was largely diminished in liver and kidney microsomes, by niflumic acid, a selective inhibitor UGT1A9. 27032077 3 65 theme AαC-HON 619:625 arg1 -Gluc 629:633 AαC-HON(2)-Gluc 619:633 AαC-HON(2)-Gluc 619:633 The genotoxic N-hydroxylated metabolite of AαC, 2-hydroxyamino-9H-pyrido[2,3-b]indole (HONH-AαC), undergoes glucuronidation to form the isomeric glucuronide (Gluc) conjugates N(2)-(β-d-glucosidurony1)-2-hydroxyamino-9H-pyrido[2,3-b]indole (AαC-HON(2)-Gluc) and O-(β-d-glucosidurony1)-2-hydroxyamino-9H-pyrido[2,3-b]indole (AαC-HN(2)-O-Gluc). 27032077 8 66 theme PhIP 1564:1567 arg1 pyridine 1514:1521 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine 1468:1521 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine (HONH-PhIP) 1468:1533 UGT were reported to catalyze the formation of isomeric Gluc conjugates at the N(2) and N3 atoms of 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine (HONH-PhIP), the genotoxic metabolite of PhIP. 27032077 8 66 theme PhIP 1564:1567 arg1 metabolite 1550:1559 the genotoxic metabolite 1536:1559 the genotoxic metabolite of PhIP 1536:1567 UGT were reported to catalyze the formation of isomeric Gluc conjugates at the N(2) and N3 atoms of 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine (HONH-PhIP), the genotoxic metabolite of PhIP. 27032077 3 67 theme indole 611:616 arg1 conjugates 543:552 the isomeric glucuronide (Gluc) conjugates 511:552 the isomeric glucuronide (Gluc) conjugates N(2)-(β-d-glucosidurony1)-2-hydroxyamino-9H-pyrido[2,3-b]indole (AαC-HON(2)-Gluc) and O-(β-d-glucosidurony1)-2-hydroxyamino-9H-pyrido[2,3-b]indole (AαC-HN(2)-O-Gluc) 511:718 The genotoxic N-hydroxylated metabolite of AαC, 2-hydroxyamino-9H-pyrido[2,3-b]indole (HONH-AαC), undergoes glucuronidation to form the isomeric glucuronide (Gluc) conjugates N(2)-(β-d-glucosidurony1)-2-hydroxyamino-9H-pyrido[2,3-b]indole (AαC-HON(2)-Gluc) and O-(β-d-glucosidurony1)-2-hydroxyamino-9H-pyrido[2,3-b]indole (AαC-HN(2)-O-Gluc). 27032077 1 68 theme 2-amino-1-methyl-6-phenylimidazo[4,5-b 120:157 arg1 pyridine 159:166 2-Amino-9H-pyrido[2,3-b]indole (AαC) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine 79:166 pyridine 159:166 2-Amino-9H-pyrido[2,3-b]indole (AαC) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are carcinogenic heterocyclic aromatic amines (HAA) that arise during the burning of tobacco and cooking of meats. 27032077 1 68 theme 2-amino-1-methyl-6-phenylimidazo[4,5-b 120:157 arg1 amines 214:219 carcinogenic heterocyclic aromatic amines 179:219 carcinogenic heterocyclic aromatic amines (HAA) that arise during the burning of tobacco and cooking of meats 179:287 2-Amino-9H-pyrido[2,3-b]indole (AαC) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are carcinogenic heterocyclic aromatic amines (HAA) that arise during the burning of tobacco and cooking of meats. 27032077 1 68 theme 2-amino-1-methyl-6-phenylimidazo[4,5-b 120:157 arg1 AαC 111:113 2-Amino-9H-pyrido[2,3-b]indole (AαC) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine 79:166 AαC 111:113 2-Amino-9H-pyrido[2,3-b]indole (AαC) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are carcinogenic heterocyclic aromatic amines (HAA) that arise during the burning of tobacco and cooking of meats. 27032077 3 69 theme indole 694:699 arg1 conjugates 543:552 the isomeric glucuronide (Gluc) conjugates 511:552 the isomeric glucuronide (Gluc) conjugates N(2)-(β-d-glucosidurony1)-2-hydroxyamino-9H-pyrido[2,3-b]indole (AαC-HON(2)-Gluc) and O-(β-d-glucosidurony1)-2-hydroxyamino-9H-pyrido[2,3-b]indole (AαC-HN(2)-O-Gluc) 511:718 The genotoxic N-hydroxylated metabolite of AαC, 2-hydroxyamino-9H-pyrido[2,3-b]indole (HONH-AαC), undergoes glucuronidation to form the isomeric glucuronide (Gluc) conjugates N(2)-(β-d-glucosidurony1)-2-hydroxyamino-9H-pyrido[2,3-b]indole (AαC-HON(2)-Gluc) and O-(β-d-glucosidurony1)-2-hydroxyamino-9H-pyrido[2,3-b]indole (AαC-HN(2)-O-Gluc). 27032077 6 70 theme kidney 1182:1187 arg1 microsomes 1189:1198 liver and kidney microsomes 1172:1198 liver and kidney microsomes 1172:1198 AαC-HN(2)-O-Gluc formation was largely diminished in liver and kidney microsomes, by niflumic acid, a selective inhibitor UGT1A9. 27032077 11 71 theme detoxicated 2097:2107 arg1 isomers 2119:2125 their detoxicated N(2)-Gluc isomers 2091:2125 their detoxicated N(2)-Gluc isomers 2091:2125 UGT1A9, an abundant UGT isoform expressed in human liver and kidney, preferentially forms the O-linked Gluc conjugates of HONH-AαC and HONH-PhIP as opposed to their detoxicated N(2)-Gluc isomers. 27032077 5 72 theme liver 1026:1030 arg1 microsomes 1043:1052 liver and kidney microsomes 1026:1052 liver and kidney microsomes 1026:1052 We measured the rates of formation of AαC-HON(2)-Gluc and AαC-HN(2)-O-Gluc in human organs: highest activity occurred with liver and kidney microsomes, and lesser activity was found with colon and rectum microsomes. 27032077 10 73 theme HONH-PhIP 1829:1837 arg1 atom 1864:1867 not the N3 imidazole atom 1843:1867 not the N3 imidazole atom of the oxime tautomer of HONH-PhIP 1843:1902 The product ion spectra of this Gluc conjugate acquired by ion trap mass spectrometry revealed that the Gluc moiety was linked to the oxygen atom of HONH-PhIP and not the N3 imidazole atom of the oxime tautomer of HONH-PhIP as was originally proposed. 27032077 10 73 theme HONH-PhIP 1829:1837 arg1 atom 1821:1824 the oxygen atom 1810:1824 the oxygen atom of HONH-PhIP 1810:1837 The product ion spectra of this Gluc conjugate acquired by ion trap mass spectrometry revealed that the Gluc moiety was linked to the oxygen atom of HONH-PhIP and not the N3 imidazole atom of the oxime tautomer of HONH-PhIP as was originally proposed. 27032077 5 74 theme kidney 1036:1041 arg1 microsomes 1043:1052 liver and kidney microsomes 1026:1052 liver and kidney microsomes 1026:1052 We measured the rates of formation of AαC-HON(2)-Gluc and AαC-HN(2)-O-Gluc in human organs: highest activity occurred with liver and kidney microsomes, and lesser activity was found with colon and rectum microsomes. 27032077 3 75 theme N-hydroxylated 393:406 arg1 metabolite 408:417 The genotoxic N-hydroxylated metabolite 379:417 The genotoxic N-hydroxylated metabolite 379:417 The genotoxic N-hydroxylated metabolite of AαC, 2-hydroxyamino-9H-pyrido[2,3-b]indole (HONH-AαC), undergoes glucuronidation to form the isomeric glucuronide (Gluc) conjugates N(2)-(β-d-glucosidurony1)-2-hydroxyamino-9H-pyrido[2,3-b]indole (AαC-HON(2)-Gluc) and O-(β-d-glucosidurony1)-2-hydroxyamino-9H-pyrido[2,3-b]indole (AαC-HN(2)-O-Gluc). 27032077 11 76 theme -Gluc 2113:2117 arg1 isomers 2119:2125 their detoxicated N(2)-Gluc isomers 2091:2125 their detoxicated N(2)-Gluc isomers 2091:2125 UGT1A9, an abundant UGT isoform expressed in human liver and kidney, preferentially forms the O-linked Gluc conjugates of HONH-AαC and HONH-PhIP as opposed to their detoxicated N(2)-Gluc isomers. 27032077 6 77 theme selective 1221:1229 arg1 inhibitor 1231:1239 a selective inhibitor UGT1A9 1219:1246 a selective inhibitor UGT1A9 1219:1246 AαC-HN(2)-O-Gluc formation was largely diminished in liver and kidney microsomes, by niflumic acid, a selective inhibitor UGT1A9. 27032077 6 77 theme selective 1221:1229 arg1 acid 1213:1216 niflumic acid 1204:1216 niflumic acid 1204:1216 AαC-HN(2)-O-Gluc formation was largely diminished in liver and kidney microsomes, by niflumic acid, a selective inhibitor UGT1A9. 27032077 5 78 theme highest 995:1001 arg1 activity 1003:1010 highest activity 995:1010 highest activity 995:1010 We measured the rates of formation of AαC-HON(2)-Gluc and AαC-HN(2)-O-Gluc in human organs: highest activity occurred with liver and kidney microsomes, and lesser activity was found with colon and rectum microsomes. 27032077 12 79 theme regioselective 2132:2145 arg1 O-glucuronidation 2147:2163 The regioselective O-glucuronidation 2128:2163 The regioselective O-glucuronidation 2128:2163 The regioselective O-glucuronidation of HONH-AαC and HONH-PhIP, by UGT1A9, is a mechanism of bioactivation of these ubiquitous HAAs. 27032077 12 79 theme regioselective 2132:2145 arg1 mechanism 2208:2216 a mechanism 2206:2216 a mechanism of bioactivation of these ubiquitous HAAs 2206:2258 The regioselective O-glucuronidation of HONH-AαC and HONH-PhIP, by UGT1A9, is a mechanism of bioactivation of these ubiquitous HAAs. 27032077 11 80 theme abundant 1943:1950 arg1 isoform 1956:1962 an abundant UGT isoform 1940:1962 an abundant UGT isoform expressed in human liver and kidney 1940:1998 UGT1A9, an abundant UGT isoform expressed in human liver and kidney, preferentially forms the O-linked Gluc conjugates of HONH-AαC and HONH-PhIP as opposed to their detoxicated N(2)-Gluc isomers. 27032077 11 80 theme abundant 1943:1950 arg1 UGT1A9 1932:1937 UGT1A9 1932:1937 UGT1A9 1932:1937 UGT1A9, an abundant UGT isoform expressed in human liver and kidney, preferentially forms the O-linked Gluc conjugates of HONH-AαC and HONH-PhIP as opposed to their detoxicated N(2)-Gluc isomers. 27032077 4 81 theme AαC-HON 721:727 arg1 metabolite 749:758 a stable metabolite 740:758 a stable metabolite 740:758 AαC-HON(2)-Gluc is a stable metabolite but AαC-HN(2)-O-Gluc is a biologically reactive intermediate, which covalently adducts to DNA at levels that are 20-fold higher than HONH-AαC. 27032077 4 81 theme AαC-HON 721:727 arg1 -Gluc 731:735 AαC-HON(2)-Gluc 721:735 AαC-HON(2)-Gluc 721:735 AαC-HON(2)-Gluc is a stable metabolite but AαC-HN(2)-O-Gluc is a biologically reactive intermediate, which covalently adducts to DNA at levels that are 20-fold higher than HONH-AαC. 27032077 0 82 theme Aromatic 30:37 arg1 Amines 39:44 Heterocyclic Aromatic Amines 17:44 Heterocyclic Aromatic Amines 17:44 Bioactivation of Heterocyclic Aromatic Amines by UDP Glucuronosyltransferases. 27032077 12 83 theme HONH-PhIP 2181:2189 arg1 O-glucuronidation 2147:2163 The regioselective O-glucuronidation 2128:2163 The regioselective O-glucuronidation 2128:2163 The regioselective O-glucuronidation of HONH-AαC and HONH-PhIP, by UGT1A9, is a mechanism of bioactivation of these ubiquitous HAAs. 27032077 12 83 theme HONH-PhIP 2181:2189 arg1 mechanism 2208:2216 a mechanism 2206:2216 a mechanism of bioactivation of these ubiquitous HAAs 2206:2258 The regioselective O-glucuronidation of HONH-AαC and HONH-PhIP, by UGT1A9, is a mechanism of bioactivation of these ubiquitous HAAs. 27032077 12 84 theme HONH-AαC 2168:2175 arg1 O-glucuronidation 2147:2163 The regioselective O-glucuronidation 2128:2163 The regioselective O-glucuronidation 2128:2163 The regioselective O-glucuronidation of HONH-AαC and HONH-PhIP, by UGT1A9, is a mechanism of bioactivation of these ubiquitous HAAs. 27032077 12 84 theme HONH-AαC 2168:2175 arg1 mechanism 2208:2216 a mechanism 2206:2216 a mechanism of bioactivation of these ubiquitous HAAs 2206:2258 The regioselective O-glucuronidation of HONH-AαC and HONH-PhIP, by UGT1A9, is a mechanism of bioactivation of these ubiquitous HAAs. 27032077 3 85 dep -O-Gluc 711:717 arg1 2 709:709 2 709:709 2 709:709 The genotoxic N-hydroxylated metabolite of AαC, 2-hydroxyamino-9H-pyrido[2,3-b]indole (HONH-AαC), undergoes glucuronidation to form the isomeric glucuronide (Gluc) conjugates N(2)-(β-d-glucosidurony1)-2-hydroxyamino-9H-pyrido[2,3-b]indole (AαC-HON(2)-Gluc) and O-(β-d-glucosidurony1)-2-hydroxyamino-9H-pyrido[2,3-b]indole (AαC-HN(2)-O-Gluc). 27032077 5 86 theme -Gluc 951:955 arg1 formation 928:936 formation 928:936 formation of AαC-HON(2)-Gluc and AαC-HN(2)-O-Gluc 928:976 We measured the rates of formation of AαC-HON(2)-Gluc and AαC-HN(2)-O-Gluc in human organs: highest activity occurred with liver and kidney microsomes, and lesser activity was found with colon and rectum microsomes. 27032077 9 87 theme higher 1650:1655 arg1 levels 1657:1662 higher levels 1650:1662 higher levels than HONH-PhIP 1650:1677 However, we found that the N3-Gluc of HONH-PhIP also covalently bound to DNA at higher levels than HONH-PhIP. 27032077 8 88 theme Gluc 1424:1427 arg1 conjugates 1429:1438 isomeric Gluc conjugates 1415:1438 isomeric Gluc conjugates 1415:1438 UGT were reported to catalyze the formation of isomeric Gluc conjugates at the N(2) and N3 atoms of 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine (HONH-PhIP), the genotoxic metabolite of PhIP. 27032077 3 89 theme Gluc 537:540 arg1 conjugates 543:552 the isomeric glucuronide (Gluc) conjugates 511:552 the isomeric glucuronide (Gluc) conjugates N(2)-(β-d-glucosidurony1)-2-hydroxyamino-9H-pyrido[2,3-b]indole (AαC-HON(2)-Gluc) and O-(β-d-glucosidurony1)-2-hydroxyamino-9H-pyrido[2,3-b]indole (AαC-HN(2)-O-Gluc) 511:718 The genotoxic N-hydroxylated metabolite of AαC, 2-hydroxyamino-9H-pyrido[2,3-b]indole (HONH-AαC), undergoes glucuronidation to form the isomeric glucuronide (Gluc) conjugates N(2)-(β-d-glucosidurony1)-2-hydroxyamino-9H-pyrido[2,3-b]indole (AαC-HON(2)-Gluc) and O-(β-d-glucosidurony1)-2-hydroxyamino-9H-pyrido[2,3-b]indole (AαC-HN(2)-O-Gluc). 27032077 5 90 theme lesser 1059:1064 arg1 activity 1066:1073 lesser activity 1059:1073 lesser activity 1059:1073 We measured the rates of formation of AαC-HON(2)-Gluc and AαC-HN(2)-O-Gluc in human organs: highest activity occurred with liver and kidney microsomes, and lesser activity was found with colon and rectum microsomes. 27032077 5 91 theme formation 928:936 arg1 rates 919:923 the rates 915:923 the rates of formation of AαC-HON(2)-Gluc and AαC-HN(2)-O-Gluc in human organs 915:992 We measured the rates of formation of AαC-HON(2)-Gluc and AαC-HN(2)-O-Gluc in human organs: highest activity occurred with liver and kidney microsomes, and lesser activity was found with colon and rectum microsomes. 27032077 10 92 theme N3 1851:1852 arg1 atom 1864:1867 not the N3 imidazole atom 1843:1867 not the N3 imidazole atom of the oxime tautomer of HONH-PhIP 1843:1902 The product ion spectra of this Gluc conjugate acquired by ion trap mass spectrometry revealed that the Gluc moiety was linked to the oxygen atom of HONH-PhIP and not the N3 imidazole atom of the oxime tautomer of HONH-PhIP as was originally proposed. 27032077 10 93 theme product 1684:1690 arg1 spectra 1696:1702 The product ion spectra 1680:1702 The product ion spectra of this Gluc conjugate acquired by ion trap mass spectrometry 1680:1764 The product ion spectra of this Gluc conjugate acquired by ion trap mass spectrometry revealed that the Gluc moiety was linked to the oxygen atom of HONH-PhIP and not the N3 imidazole atom of the oxime tautomer of HONH-PhIP as was originally proposed. 27032077 3 94 theme glucuronide 524:534 arg1 conjugates 543:552 the isomeric glucuronide (Gluc) conjugates 511:552 the isomeric glucuronide (Gluc) conjugates N(2)-(β-d-glucosidurony1)-2-hydroxyamino-9H-pyrido[2,3-b]indole (AαC-HON(2)-Gluc) and O-(β-d-glucosidurony1)-2-hydroxyamino-9H-pyrido[2,3-b]indole (AαC-HN(2)-O-Gluc) 511:718 The genotoxic N-hydroxylated metabolite of AαC, 2-hydroxyamino-9H-pyrido[2,3-b]indole (HONH-AαC), undergoes glucuronidation to form the isomeric glucuronide (Gluc) conjugates N(2)-(β-d-glucosidurony1)-2-hydroxyamino-9H-pyrido[2,3-b]indole (AαC-HON(2)-Gluc) and O-(β-d-glucosidurony1)-2-hydroxyamino-9H-pyrido[2,3-b]indole (AαC-HN(2)-O-Gluc). 27032077 8 95 theme 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b 1468:1512 arg1 pyridine 1514:1521 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine 1468:1521 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine (HONH-PhIP) 1468:1533 UGT were reported to catalyze the formation of isomeric Gluc conjugates at the N(2) and N3 atoms of 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine (HONH-PhIP), the genotoxic metabolite of PhIP. 27032077 8 95 theme 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b 1468:1512 arg1 metabolite 1550:1559 the genotoxic metabolite 1536:1559 the genotoxic metabolite of PhIP 1536:1567 UGT were reported to catalyze the formation of isomeric Gluc conjugates at the N(2) and N3 atoms of 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine (HONH-PhIP), the genotoxic metabolite of PhIP. 27032077 8 95 theme 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b 1468:1512 arg1 HONH-PhIP 1524:1532 HONH-PhIP 1524:1532 HONH-PhIP 1524:1532 UGT were reported to catalyze the formation of isomeric Gluc conjugates at the N(2) and N3 atoms of 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine (HONH-PhIP), the genotoxic metabolite of PhIP. 27032077 5 96 theme AαC-HON 941:947 arg1 -Gluc 951:955 AαC-HON(2)-Gluc 941:955 AαC-HON(2)-Gluc 941:955 We measured the rates of formation of AαC-HON(2)-Gluc and AαC-HN(2)-O-Gluc in human organs: highest activity occurred with liver and kidney microsomes, and lesser activity was found with colon and rectum microsomes. 27032077 5 97 from rates 919:923 arg1 organs 987:992 human organs 981:992 human organs 981:992 We measured the rates of formation of AαC-HON(2)-Gluc and AαC-HN(2)-O-Gluc in human organs: highest activity occurred with liver and kidney microsomes, and lesser activity was found with colon and rectum microsomes. 27032077 5 98 dep -O-Gluc 970:976 arg1 2 968:968 2 968:968 2 968:968 We measured the rates of formation of AαC-HON(2)-Gluc and AαC-HN(2)-O-Gluc in human organs: highest activity occurred with liver and kidney microsomes, and lesser activity was found with colon and rectum microsomes. 27032077 10 99 theme conjugate 1717:1725 arg1 spectra 1696:1702 The product ion spectra 1680:1702 The product ion spectra of this Gluc conjugate acquired by ion trap mass spectrometry 1680:1764 The product ion spectra of this Gluc conjugate acquired by ion trap mass spectrometry revealed that the Gluc moiety was linked to the oxygen atom of HONH-PhIP and not the N3 imidazole atom of the oxime tautomer of HONH-PhIP as was originally proposed. 27032077 4 100 theme AαC-HN 764:769 arg1 intermediate 808:819 a biologically reactive intermediate 784:819 a biologically reactive intermediate 784:819 AαC-HON(2)-Gluc is a stable metabolite but AαC-HN(2)-O-Gluc is a biologically reactive intermediate, which covalently adducts to DNA at levels that are 20-fold higher than HONH-AαC. 27032077 4 100 theme AαC-HN 764:769 arg1 -O-Gluc 773:779 AαC-HN(2)-O-Gluc 764:779 AαC-HN(2)-O-Gluc 764:779 AαC-HON(2)-Gluc is a stable metabolite but AαC-HN(2)-O-Gluc is a biologically reactive intermediate, which covalently adducts to DNA at levels that are 20-fold higher than HONH-AαC. 27032077 3 101 theme AαC 422:424 arg1 HONH-AαC 466:473 HONH-AαC 466:473 HONH-AαC 466:473 The genotoxic N-hydroxylated metabolite of AαC, 2-hydroxyamino-9H-pyrido[2,3-b]indole (HONH-AαC), undergoes glucuronidation to form the isomeric glucuronide (Gluc) conjugates N(2)-(β-d-glucosidurony1)-2-hydroxyamino-9H-pyrido[2,3-b]indole (AαC-HON(2)-Gluc) and O-(β-d-glucosidurony1)-2-hydroxyamino-9H-pyrido[2,3-b]indole (AαC-HN(2)-O-Gluc). 27032077 3 101 theme AαC 422:424 arg1 indole 458:463 AαC, 2-hydroxyamino-9H-pyrido[2,3-b]indole 422:463 indole 458:463 The genotoxic N-hydroxylated metabolite of AαC, 2-hydroxyamino-9H-pyrido[2,3-b]indole (HONH-AαC), undergoes glucuronidation to form the isomeric glucuronide (Gluc) conjugates N(2)-(β-d-glucosidurony1)-2-hydroxyamino-9H-pyrido[2,3-b]indole (AαC-HON(2)-Gluc) and O-(β-d-glucosidurony1)-2-hydroxyamino-9H-pyrido[2,3-b]indole (AαC-HN(2)-O-Gluc). 27032077 8 102 theme pyridine 1514:1521 arg1 N 1447:1447 N(2) 1447:1450 N(2) 1447:1450 UGT were reported to catalyze the formation of isomeric Gluc conjugates at the N(2) and N3 atoms of 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine (HONH-PhIP), the genotoxic metabolite of PhIP. 27032077 8 102 theme pyridine 1514:1521 arg1 atoms 1459:1463 N3 atoms 1456:1463 N3 atoms 1456:1463 UGT were reported to catalyze the formation of isomeric Gluc conjugates at the N(2) and N3 atoms of 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine (HONH-PhIP), the genotoxic metabolite of PhIP. 25642942 7 0 theme healthy 1126:1132 arg1 individuals 1134:1144 healthy individuals 1126:1144 healthy individuals 1126:1144 The competition ELISA detected lubricin in blood samples from healthy individuals but not from patients with CACP, indicating blood can be used in a diagnostic test for patients suspected of having CACP. 25642942 4 1 theme peptide 698:704 arg1 KEPAPTTT 712:719 the peptide motif KEPAPTTT 694:719 the peptide motif KEPAPTTT 694:719 We found the mAbs all recognized epitopes containing O-linked oligosaccharides conjugated to the peptide motif KEPAPTTT. 25642942 0 2 theme several 98:104 arg1 species 106:112 several species 98:112 several species 98:112 Anti-lubricin monoclonal antibodies created using lubricin-knockout mice immunodetect lubricin in several species and in patients with healthy and diseased joints. 25642942 8 3 theme degradation 1312:1322 arg1 fragments 1324:1332 degradation fragments 1312:1332 degradation fragments from synovial fluid 1312:1352 Lubricin epitopes in blood do not represent degradation fragments from synovial fluid. 25642942 5 4 theme western 725:731 arg1 blot 733:736 western blot 725:736 western blot 725:736 By western blot, the mAbs detected lubricin in 1 μl of synovial fluid from several animal species, including human. 25642942 5 5 from μl 771:772 arg1 species 812:818 several animal species 797:818 several animal species 797:818 By western blot, the mAbs detected lubricin in 1 μl of synovial fluid from several animal species, including human. 25642942 5 5 from μl 771:772 arg1 human 831:835 human 831:835 human 831:835 By western blot, the mAbs detected lubricin in 1 μl of synovial fluid from several animal species, including human. 25642942 9 6 from activity 1558:1565 arg1 fluid 1579:1583 synovial fluid 1570:1583 synovial fluid 1570:1583 Therefore, although blood lubricin levels did not differentiate patients with inflammatory joint disease from healthy controls, epitope-specific anti-lubricin mAbs could be useful for monitoring disease activity in synovial fluid. 25642942 3 7 theme competition 528:538 arg1 assay 546:550 a competition ELISA assay 526:550 a competition ELISA assay to measure lubricin in synovial fluid and blood 526:598 We determined each mAb's binding epitope, sensitivity, and specificity using biologic samples and recombinant lubricin sub-domains, and we also developed a competition ELISA assay to measure lubricin in synovial fluid and blood. 25642942 6 8 theme vara-pericarditis 994:1010 arg1 syndrome 1012:1019 camptodactyly-arthropathy-coxa vara-pericarditis syndrome 963:1019 camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP) 963:1026 The mAbs were specific for lubricin since they did not cross-react with other synovial fluid constituents from patients with camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP), who genetically lack this protein. 25642942 6 8 theme vara-pericarditis 994:1010 arg1 CACP 1022:1025 CACP 1022:1025 CACP 1022:1025 The mAbs were specific for lubricin since they did not cross-react with other synovial fluid constituents from patients with camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP), who genetically lack this protein. 25642942 9 9 theme synovial 1570:1577 arg1 fluid 1579:1583 synovial fluid 1570:1583 synovial fluid 1570:1583 Therefore, although blood lubricin levels did not differentiate patients with inflammatory joint disease from healthy controls, epitope-specific anti-lubricin mAbs could be useful for monitoring disease activity in synovial fluid. 25642942 3 10 theme ELISA 540:544 arg1 assay 546:550 a competition ELISA assay 526:550 a competition ELISA assay to measure lubricin in synovial fluid and blood 526:598 We determined each mAb's binding epitope, sensitivity, and specificity using biologic samples and recombinant lubricin sub-domains, and we also developed a competition ELISA assay to measure lubricin in synovial fluid and blood. 25642942 3 11 theme recombinant 470:480 arg1 sub-domains 491:501 recombinant lubricin sub-domains 470:501 recombinant lubricin sub-domains 470:501 We determined each mAb's binding epitope, sensitivity, and specificity using biologic samples and recombinant lubricin sub-domains, and we also developed a competition ELISA assay to measure lubricin in synovial fluid and blood. 25642942 7 12 from patients 1159:1166 arg1 samples 1113:1119 blood samples 1107:1119 blood samples from healthy individuals but not from patients with CACP 1107:1176 The competition ELISA detected lubricin in blood samples from healthy individuals but not from patients with CACP, indicating blood can be used in a diagnostic test for patients suspected of having CACP. 25642942 5 13 theme fluid 786:790 arg1 μl 771:772 1 μl 769:772 1 μl of synovial fluid from several animal species, including human 769:835 By western blot, the mAbs detected lubricin in 1 μl of synovial fluid from several animal species, including human. 25642942 2 14 theme deficient 281:289 arg1 mice 264:267 mice 264:267 mice genetically deficient for lubricin (Prg4-/-) with purified human lubricin 264:341 We immunized mice genetically deficient for lubricin (Prg4-/-) with purified human lubricin, and generated several mAbs. 25642942 9 15 theme joint 1446:1450 arg1 disease 1452:1458 inflammatory joint disease 1433:1458 inflammatory joint disease from healthy controls 1433:1480 Therefore, although blood lubricin levels did not differentiate patients with inflammatory joint disease from healthy controls, epitope-specific anti-lubricin mAbs could be useful for monitoring disease activity in synovial fluid. 25642942 6 16 theme camptodactyly-arthropathy-coxa 963:992 arg1 syndrome 1012:1019 camptodactyly-arthropathy-coxa vara-pericarditis syndrome 963:1019 camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP) 963:1026 The mAbs were specific for lubricin since they did not cross-react with other synovial fluid constituents from patients with camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP), who genetically lack this protein. 25642942 6 16 theme camptodactyly-arthropathy-coxa 963:992 arg1 CACP 1022:1025 CACP 1022:1025 CACP 1022:1025 The mAbs were specific for lubricin since they did not cross-react with other synovial fluid constituents from patients with camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP), who genetically lack this protein. 25642942 0 17 theme lubricin-knockout 50:66 arg1 mice 68:71 lubricin-knockout mice 50:71 lubricin-knockout mice 50:71 Anti-lubricin monoclonal antibodies created using lubricin-knockout mice immunodetect lubricin in several species and in patients with healthy and diseased joints. 25642942 6 18 with patients 949:956 arg1 syndrome 1012:1019 camptodactyly-arthropathy-coxa vara-pericarditis syndrome 963:1019 camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP) 963:1026 The mAbs were specific for lubricin since they did not cross-react with other synovial fluid constituents from patients with camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP), who genetically lack this protein. 25642942 6 18 with patients 949:956 arg1 CACP 1022:1025 CACP 1022:1025 CACP 1022:1025 The mAbs were specific for lubricin since they did not cross-react with other synovial fluid constituents from patients with camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP), who genetically lack this protein. 25642942 0 19 theme monoclonal 14:23 arg1 antibodies 25:34 Anti-lubricin monoclonal antibodies 0:34 Anti-lubricin monoclonal antibodies created using lubricin-knockout mice 0:71 Anti-lubricin monoclonal antibodies created using lubricin-knockout mice immunodetect lubricin in several species and in patients with healthy and diseased joints. 25642942 7 20 used used 1203:1206 arg2 blood 1190:1194 blood 1190:1194 blood 1190:1194 The competition ELISA detected lubricin in blood samples from healthy individuals but not from patients with CACP, indicating blood can be used in a diagnostic test for patients suspected of having CACP. 25642942 0 21 with patients 121:128 arg1 joints 156:161 healthy and diseased joints 135:161 healthy and diseased joints 135:161 Anti-lubricin monoclonal antibodies created using lubricin-knockout mice immunodetect lubricin in several species and in patients with healthy and diseased joints. 25642942 9 22 theme disease 1550:1556 arg1 activity 1558:1565 disease activity 1550:1565 disease activity in synovial fluid 1550:1583 Therefore, although blood lubricin levels did not differentiate patients with inflammatory joint disease from healthy controls, epitope-specific anti-lubricin mAbs could be useful for monitoring disease activity in synovial fluid. 25642942 1 23 theme gene 189:192 arg1 PRG4 194:197 the gene PRG4 185:197 the gene PRG4 185:197 Lubricin, encoded by the gene PRG4, is the principal lubricant in articulating joints. 25642942 0 24 theme Anti-lubricin 0:12 arg1 antibodies 25:34 Anti-lubricin monoclonal antibodies 0:34 Anti-lubricin monoclonal antibodies created using lubricin-knockout mice 0:71 Anti-lubricin monoclonal antibodies created using lubricin-knockout mice immunodetect lubricin in several species and in patients with healthy and diseased joints. 25642942 4 25 theme O-linked 654:661 arg1 oligosaccharides 663:678 O-linked oligosaccharides 654:678 O-linked oligosaccharides conjugated to the peptide motif KEPAPTTT 654:719 We found the mAbs all recognized epitopes containing O-linked oligosaccharides conjugated to the peptide motif KEPAPTTT. 25642942 5 26 theme several 797:803 arg1 species 812:818 several animal species 797:818 several animal species 797:818 By western blot, the mAbs detected lubricin in 1 μl of synovial fluid from several animal species, including human. 25642942 5 26 theme several 797:803 arg1 human 831:835 human 831:835 human 831:835 By western blot, the mAbs detected lubricin in 1 μl of synovial fluid from several animal species, including human. 25642942 7 27 theme competition 1068:1078 arg1 ELISA 1080:1084 The competition ELISA 1064:1084 The competition ELISA 1064:1084 The competition ELISA detected lubricin in blood samples from healthy individuals but not from patients with CACP, indicating blood can be used in a diagnostic test for patients suspected of having CACP. 25642942 8 28 from epitopes 1277:1284 arg1 blood 1289:1293 blood 1289:1293 blood 1289:1293 Lubricin epitopes in blood do not represent degradation fragments from synovial fluid. 25642942 7 29 theme blood 1107:1111 arg1 samples 1113:1119 blood samples 1107:1119 blood samples from healthy individuals but not from patients with CACP 1107:1176 The competition ELISA detected lubricin in blood samples from healthy individuals but not from patients with CACP, indicating blood can be used in a diagnostic test for patients suspected of having CACP. 25642942 3 30 theme biologic 449:456 arg1 samples 458:464 biologic samples 449:464 biologic samples 449:464 We determined each mAb's binding epitope, sensitivity, and specificity using biologic samples and recombinant lubricin sub-domains, and we also developed a competition ELISA assay to measure lubricin in synovial fluid and blood. 25642942 5 31 theme animal 805:810 arg1 species 812:818 several animal species 797:818 several animal species 797:818 By western blot, the mAbs detected lubricin in 1 μl of synovial fluid from several animal species, including human. 25642942 5 31 theme animal 805:810 arg1 human 831:835 human 831:835 human 831:835 By western blot, the mAbs detected lubricin in 1 μl of synovial fluid from several animal species, including human. 25642942 0 32 theme healthy 135:141 arg1 joints 156:161 healthy and diseased joints 135:161 healthy and diseased joints 135:161 Anti-lubricin monoclonal antibodies created using lubricin-knockout mice immunodetect lubricin in several species and in patients with healthy and diseased joints. 25642942 9 33 from controls 1473:1480 arg1 disease 1452:1458 inflammatory joint disease 1433:1458 inflammatory joint disease from healthy controls 1433:1480 Therefore, although blood lubricin levels did not differentiate patients with inflammatory joint disease from healthy controls, epitope-specific anti-lubricin mAbs could be useful for monitoring disease activity in synovial fluid. 25642942 9 34 theme inflammatory 1433:1444 arg1 disease 1452:1458 inflammatory joint disease 1433:1458 inflammatory joint disease from healthy controls 1433:1480 Therefore, although blood lubricin levels did not differentiate patients with inflammatory joint disease from healthy controls, epitope-specific anti-lubricin mAbs could be useful for monitoring disease activity in synovial fluid. 25642942 3 35 theme binding 397:403 arg1 epitope 405:411 each mAb's binding epitope 386:411 each mAb's binding epitope 386:411 We determined each mAb's binding epitope, sensitivity, and specificity using biologic samples and recombinant lubricin sub-domains, and we also developed a competition ELISA assay to measure lubricin in synovial fluid and blood. 25642942 9 36 theme epitope-specific 1483:1498 arg1 mAbs 1514:1517 epitope-specific anti-lubricin mAbs 1483:1517 epitope-specific anti-lubricin mAbs 1483:1517 Therefore, although blood lubricin levels did not differentiate patients with inflammatory joint disease from healthy controls, epitope-specific anti-lubricin mAbs could be useful for monitoring disease activity in synovial fluid. 25642942 9 37 theme healthy 1465:1471 arg1 controls 1473:1480 healthy controls 1465:1480 healthy controls 1465:1480 Therefore, although blood lubricin levels did not differentiate patients with inflammatory joint disease from healthy controls, epitope-specific anti-lubricin mAbs could be useful for monitoring disease activity in synovial fluid. 25642942 8 38 theme Lubricin 1268:1275 arg1 epitopes 1277:1284 Lubricin epitopes 1268:1284 Lubricin epitopes in blood 1268:1293 Lubricin epitopes in blood do not represent degradation fragments from synovial fluid. 25642942 6 39 theme fluid 925:929 arg1 constituents 931:942 other synovial fluid constituents 910:942 other synovial fluid constituents from patients with camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP), who genetically lack this protein 910:1061 The mAbs were specific for lubricin since they did not cross-react with other synovial fluid constituents from patients with camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP), who genetically lack this protein. 25642942 0 40 theme diseased 147:154 arg1 joints 156:161 healthy and diseased joints 135:161 healthy and diseased joints 135:161 Anti-lubricin monoclonal antibodies created using lubricin-knockout mice immunodetect lubricin in several species and in patients with healthy and diseased joints. 25642942 9 41 theme anti-lubricin 1500:1512 arg1 mAbs 1514:1517 epitope-specific anti-lubricin mAbs 1483:1517 epitope-specific anti-lubricin mAbs 1483:1517 Therefore, although blood lubricin levels did not differentiate patients with inflammatory joint disease from healthy controls, epitope-specific anti-lubricin mAbs could be useful for monitoring disease activity in synovial fluid. 25642942 1 42 theme articulating 230:241 arg1 joints 243:248 articulating joints 230:248 articulating joints 230:248 Lubricin, encoded by the gene PRG4, is the principal lubricant in articulating joints. 25642942 6 43 from patients 949:956 arg1 constituents 931:942 other synovial fluid constituents 910:942 other synovial fluid constituents from patients with camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP), who genetically lack this protein 910:1061 The mAbs were specific for lubricin since they did not cross-react with other synovial fluid constituents from patients with camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP), who genetically lack this protein. 25642942 9 44 theme blood 1375:1379 arg1 levels 1390:1395 blood lubricin levels 1375:1395 blood lubricin levels 1375:1395 Therefore, although blood lubricin levels did not differentiate patients with inflammatory joint disease from healthy controls, epitope-specific anti-lubricin mAbs could be useful for monitoring disease activity in synovial fluid. 25642942 6 45 theme synovial 916:923 arg1 constituents 931:942 other synovial fluid constituents 910:942 other synovial fluid constituents from patients with camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP), who genetically lack this protein 910:1061 The mAbs were specific for lubricin since they did not cross-react with other synovial fluid constituents from patients with camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP), who genetically lack this protein. 25642942 4 46 dep mAbs 614:617 arg1 all 619:621 all 619:621 all 619:621 We found the mAbs all recognized epitopes containing O-linked oligosaccharides conjugated to the peptide motif KEPAPTTT. 25642942 3 47 theme lubricin 482:489 arg1 sub-domains 491:501 recombinant lubricin sub-domains 470:501 recombinant lubricin sub-domains 470:501 We determined each mAb's binding epitope, sensitivity, and specificity using biologic samples and recombinant lubricin sub-domains, and we also developed a competition ELISA assay to measure lubricin in synovial fluid and blood. 25642942 5 48 theme synovial 777:784 arg1 fluid 786:790 synovial fluid 777:790 synovial fluid from several animal species, including human 777:835 By western blot, the mAbs detected lubricin in 1 μl of synovial fluid from several animal species, including human. 25642942 6 49 theme other 910:914 arg1 constituents 931:942 other synovial fluid constituents 910:942 other synovial fluid constituents from patients with camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP), who genetically lack this protein 910:1061 The mAbs were specific for lubricin since they did not cross-react with other synovial fluid constituents from patients with camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP), who genetically lack this protein. 25642942 1 50 from joints 243:248 arg1 Lubricin 164:171 Lubricin 164:171 Lubricin 164:171 Lubricin, encoded by the gene PRG4, is the principal lubricant in articulating joints. 25642942 1 50 from joints 243:248 arg1 lubricant 217:225 lubricant 217:225 lubricant 217:225 Lubricin, encoded by the gene PRG4, is the principal lubricant in articulating joints. 25642942 3 51 theme synovial 575:582 arg1 fluid 584:588 synovial fluid 575:588 synovial fluid 575:588 We determined each mAb's binding epitope, sensitivity, and specificity using biologic samples and recombinant lubricin sub-domains, and we also developed a competition ELISA assay to measure lubricin in synovial fluid and blood. 25642942 5 52 from species 812:818 arg1 μl 771:772 1 μl 769:772 1 μl of synovial fluid from several animal species, including human 769:835 By western blot, the mAbs detected lubricin in 1 μl of synovial fluid from several animal species, including human. 25642942 5 52 from species 812:818 arg1 fluid 786:790 synovial fluid 777:790 synovial fluid from several animal species, including human 777:835 By western blot, the mAbs detected lubricin in 1 μl of synovial fluid from several animal species, including human. 25642942 4 53 theme motif 706:710 arg1 KEPAPTTT 712:719 the peptide motif KEPAPTTT 694:719 the peptide motif KEPAPTTT 694:719 We found the mAbs all recognized epitopes containing O-linked oligosaccharides conjugated to the peptide motif KEPAPTTT. 25642942 7 54 from individuals 1134:1144 arg1 samples 1113:1119 blood samples 1107:1119 blood samples from healthy individuals but not from patients with CACP 1107:1176 The competition ELISA detected lubricin in blood samples from healthy individuals but not from patients with CACP, indicating blood can be used in a diagnostic test for patients suspected of having CACP. 25642942 1 55 from lubricant 217:225 arg1 joints 243:248 articulating joints 230:248 articulating joints 230:248 Lubricin, encoded by the gene PRG4, is the principal lubricant in articulating joints. 25642942 4 56 link O-linked 654:661 arg1 oligosaccharides 663:678 O-linked oligosaccharides 654:678 O-linked oligosaccharides conjugated to the peptide motif KEPAPTTT 654:719 We found the mAbs all recognized epitopes containing O-linked oligosaccharides conjugated to the peptide motif KEPAPTTT. 25642942 2 57 theme human 328:332 arg1 lubricin 334:341 purified human lubricin 319:341 purified human lubricin 319:341 We immunized mice genetically deficient for lubricin (Prg4-/-) with purified human lubricin, and generated several mAbs. 25642942 8 58 from fluid 1348:1352 arg1 fragments 1324:1332 degradation fragments 1312:1332 degradation fragments from synovial fluid 1312:1352 Lubricin epitopes in blood do not represent degradation fragments from synovial fluid. 25642942 9 59 theme lubricin 1381:1388 arg1 levels 1390:1395 blood lubricin levels 1375:1395 blood lubricin levels 1375:1395 Therefore, although blood lubricin levels did not differentiate patients with inflammatory joint disease from healthy controls, epitope-specific anti-lubricin mAbs could be useful for monitoring disease activity in synovial fluid. 25642942 7 60 with patients 1159:1166 arg1 CACP 1173:1176 CACP 1173:1176 CACP 1173:1176 The competition ELISA detected lubricin in blood samples from healthy individuals but not from patients with CACP, indicating blood can be used in a diagnostic test for patients suspected of having CACP. 25642942 8 61 theme synovial 1339:1346 arg1 fluid 1348:1352 synovial fluid 1339:1352 synovial fluid 1339:1352 Lubricin epitopes in blood do not represent degradation fragments from synovial fluid. 25642942 2 62 theme purified 319:326 arg1 lubricin 334:341 purified human lubricin 319:341 purified human lubricin 319:341 We immunized mice genetically deficient for lubricin (Prg4-/-) with purified human lubricin, and generated several mAbs. 25642942 7 63 theme diagnostic 1213:1222 arg1 test 1224:1227 a diagnostic test 1211:1227 a diagnostic test for patients suspected of having CACP 1211:1265 The competition ELISA detected lubricin in blood samples from healthy individuals but not from patients with CACP, indicating blood can be used in a diagnostic test for patients suspected of having CACP. 25642942 4 64 contain containing 643:652 arg2 oligosaccharides 663:678 O-linked oligosaccharides 654:678 O-linked oligosaccharides conjugated to the peptide motif KEPAPTTT 654:719 We found the mAbs all recognized epitopes containing O-linked oligosaccharides conjugated to the peptide motif KEPAPTTT. 25642942 4 64 contain containing 643:652 arg1 epitopes 634:641 epitopes 634:641 epitopes containing O-linked oligosaccharides conjugated to the peptide motif KEPAPTTT 634:719 We found the mAbs all recognized epitopes containing O-linked oligosaccharides conjugated to the peptide motif KEPAPTTT. 25642942 2 65 with lubricin 295:302 arg1 lubricin 334:341 purified human lubricin 319:341 purified human lubricin 319:341 We immunized mice genetically deficient for lubricin (Prg4-/-) with purified human lubricin, and generated several mAbs. 25642942 2 66 theme several 358:364 arg1 mAbs 366:369 several mAbs 358:369 several mAbs 358:369 We immunized mice genetically deficient for lubricin (Prg4-/-) with purified human lubricin, and generated several mAbs. 25642942 9 67 with patients 1419:1426 arg1 disease 1452:1458 inflammatory joint disease 1433:1458 inflammatory joint disease from healthy controls 1433:1480 Therefore, although blood lubricin levels did not differentiate patients with inflammatory joint disease from healthy controls, epitope-specific anti-lubricin mAbs could be useful for monitoring disease activity in synovial fluid. 25627821 4 0 theme mitochondrial 561:573 arg1 dysfunction 575:585 mitochondrial dysfunction 561:585 mitochondrial dysfunction 561:585 Nevertheless, the relationships among diabetes, hyperglycaemia, mitochondrial dysfunction and O-GlcNAc modifications remain unclear. 25627821 8 1 theme mitochondrial 1560:1572 arg1 metabolism 1574:1583 mitochondrial metabolism 1560:1583 mitochondrial metabolism 1560:1583 Thus, increased O-GlcNAcylation is neither sufficient nor necessary for high-glucose-induced suppression of mitochondrial metabolism in isolated cardiomyocytes. 25627821 6 2 theme significant 1150:1160 arg1 effects 1162:1168 few significant effects 1146:1168 few significant effects on mitochondrial respiration 1146:1197 Augmentation of O-GlcNAcylation with high glucose (33 mM) was associated with diminished basal and maximal cardiomyocyte respiration, a decreased mitochondrial reserve capacity and lower Complex II-dependent respiration (P<0.05); however, pharmacological or genetic modulation of O-GlcNAc modifications under normal or high glucose conditions showed few significant effects on mitochondrial respiration, suggesting that O-GlcNAc does not play a major role in regulating cardiomyocyte mitochondrial function. 25627821 6 3 theme genetic 1054:1060 arg1 modulation 1062:1071 pharmacological or genetic modulation 1035:1071 pharmacological or genetic modulation of O-GlcNAc modifications under normal or high glucose conditions 1035:1137 Augmentation of O-GlcNAcylation with high glucose (33 mM) was associated with diminished basal and maximal cardiomyocyte respiration, a decreased mitochondrial reserve capacity and lower Complex II-dependent respiration (P<0.05); however, pharmacological or genetic modulation of O-GlcNAc modifications under normal or high glucose conditions showed few significant effects on mitochondrial respiration, suggesting that O-GlcNAc does not play a major role in regulating cardiomyocyte mitochondrial function. 25627821 6 4 from effects 1162:1168 arg1 respiration 1187:1197 mitochondrial respiration 1173:1197 mitochondrial respiration 1173:1197 Augmentation of O-GlcNAcylation with high glucose (33 mM) was associated with diminished basal and maximal cardiomyocyte respiration, a decreased mitochondrial reserve capacity and lower Complex II-dependent respiration (P<0.05); however, pharmacological or genetic modulation of O-GlcNAc modifications under normal or high glucose conditions showed few significant effects on mitochondrial respiration, suggesting that O-GlcNAc does not play a major role in regulating cardiomyocyte mitochondrial function. 25627821 5 5 theme high-glucose-induced 670:689 arg1 increases 691:699 high-glucose-induced increases 670:699 high-glucose-induced increases in O-GlcNAc modifications 670:725 In the present study, we tested whether high-glucose-induced increases in O-GlcNAc modifications directly regulate mitochondrial function in isolated cardiomyocytes. 25627821 2 6 theme β-O-linked-N-acetylglucosamine 360:389 arg1 modification 421:432 the β-O-linked-N-acetylglucosamine (O-GlcNAc) post-translational modification 356:432 the β-O-linked-N-acetylglucosamine (O-GlcNAc) post-translational modification of proteins 356:444 In particular, diabetes can augment flux through accessory pathways of glucose metabolism, such as the hexosamine biosynthetic pathway (HBP), which produces the sugar donor for the β-O-linked-N-acetylglucosamine (O-GlcNAc) post-translational modification of proteins. 25627821 6 7 theme few 1146:1148 arg1 effects 1162:1168 few significant effects 1146:1168 few significant effects on mitochondrial respiration 1146:1197 Augmentation of O-GlcNAcylation with high glucose (33 mM) was associated with diminished basal and maximal cardiomyocyte respiration, a decreased mitochondrial reserve capacity and lower Complex II-dependent respiration (P<0.05); however, pharmacological or genetic modulation of O-GlcNAc modifications under normal or high glucose conditions showed few significant effects on mitochondrial respiration, suggesting that O-GlcNAc does not play a major role in regulating cardiomyocyte mitochondrial function. 25627821 6 8 theme pharmacological 1035:1049 arg1 modulation 1062:1071 pharmacological or genetic modulation 1035:1071 pharmacological or genetic modulation of O-GlcNAc modifications under normal or high glucose conditions 1035:1137 Augmentation of O-GlcNAcylation with high glucose (33 mM) was associated with diminished basal and maximal cardiomyocyte respiration, a decreased mitochondrial reserve capacity and lower Complex II-dependent respiration (P<0.05); however, pharmacological or genetic modulation of O-GlcNAc modifications under normal or high glucose conditions showed few significant effects on mitochondrial respiration, suggesting that O-GlcNAc does not play a major role in regulating cardiomyocyte mitochondrial function. 25627821 5 9 theme isolated 771:778 arg1 cardiomyocytes 780:793 isolated cardiomyocytes 771:793 isolated cardiomyocytes 771:793 In the present study, we tested whether high-glucose-induced increases in O-GlcNAc modifications directly regulate mitochondrial function in isolated cardiomyocytes. 25627821 6 10 theme mitochondrial 942:954 arg1 capacity 964:971 a decreased mitochondrial reserve capacity 930:971 a decreased mitochondrial reserve capacity 930:971 Augmentation of O-GlcNAcylation with high glucose (33 mM) was associated with diminished basal and maximal cardiomyocyte respiration, a decreased mitochondrial reserve capacity and lower Complex II-dependent respiration (P<0.05); however, pharmacological or genetic modulation of O-GlcNAc modifications under normal or high glucose conditions showed few significant effects on mitochondrial respiration, suggesting that O-GlcNAc does not play a major role in regulating cardiomyocyte mitochondrial function. 25627821 6 11 theme high 1115:1118 arg1 conditions 1128:1137 normal or high glucose conditions 1105:1137 normal or high glucose conditions 1105:1137 Augmentation of O-GlcNAcylation with high glucose (33 mM) was associated with diminished basal and maximal cardiomyocyte respiration, a decreased mitochondrial reserve capacity and lower Complex II-dependent respiration (P<0.05); however, pharmacological or genetic modulation of O-GlcNAc modifications under normal or high glucose conditions showed few significant effects on mitochondrial respiration, suggesting that O-GlcNAc does not play a major role in regulating cardiomyocyte mitochondrial function. 25627821 6 12 theme decreased 932:940 arg1 capacity 964:971 a decreased mitochondrial reserve capacity 930:971 a decreased mitochondrial reserve capacity 930:971 Augmentation of O-GlcNAcylation with high glucose (33 mM) was associated with diminished basal and maximal cardiomyocyte respiration, a decreased mitochondrial reserve capacity and lower Complex II-dependent respiration (P<0.05); however, pharmacological or genetic modulation of O-GlcNAc modifications under normal or high glucose conditions showed few significant effects on mitochondrial respiration, suggesting that O-GlcNAc does not play a major role in regulating cardiomyocyte mitochondrial function. 25627821 8 13 theme metabolism 1574:1583 arg1 suppression 1545:1555 high-glucose-induced suppression 1524:1555 high-glucose-induced suppression of mitochondrial metabolism in isolated cardiomyocytes 1524:1610 Thus, increased O-GlcNAcylation is neither sufficient nor necessary for high-glucose-induced suppression of mitochondrial metabolism in isolated cardiomyocytes. 25627821 6 14 theme cardiomyocyte 1266:1278 arg1 function 1294:1301 cardiomyocyte mitochondrial function 1266:1301 cardiomyocyte mitochondrial function 1266:1301 Augmentation of O-GlcNAcylation with high glucose (33 mM) was associated with diminished basal and maximal cardiomyocyte respiration, a decreased mitochondrial reserve capacity and lower Complex II-dependent respiration (P<0.05); however, pharmacological or genetic modulation of O-GlcNAc modifications under normal or high glucose conditions showed few significant effects on mitochondrial respiration, suggesting that O-GlcNAc does not play a major role in regulating cardiomyocyte mitochondrial function. 25627821 5 15 theme O-GlcNAc 704:711 arg1 modifications 713:725 O-GlcNAc modifications 704:725 O-GlcNAc modifications 704:725 In the present study, we tested whether high-glucose-induced increases in O-GlcNAc modifications directly regulate mitochondrial function in isolated cardiomyocytes. 25627821 2 16 mod modification 421:432 arg1 proteins 437:444 proteins 437:444 proteins 437:444 In particular, diabetes can augment flux through accessory pathways of glucose metabolism, such as the hexosamine biosynthetic pathway (HBP), which produces the sugar donor for the β-O-linked-N-acetylglucosamine (O-GlcNAc) post-translational modification of proteins. 25627821 2 16 mod modification 421:432 arg3 β-O-linked-N-acetylglucosamine 360:389 the β-O-linked-N-acetylglucosamine (O-GlcNAc) post-translational modification 356:432 the β-O-linked-N-acetylglucosamine (O-GlcNAc) post-translational modification of proteins 356:444 In particular, diabetes can augment flux through accessory pathways of glucose metabolism, such as the hexosamine biosynthetic pathway (HBP), which produces the sugar donor for the β-O-linked-N-acetylglucosamine (O-GlcNAc) post-translational modification of proteins. 25627821 2 16 mod modification 421:432 arg3 O-GlcNAc 392:399 the β-O-linked-N-acetylglucosamine (O-GlcNAc) post-translational modification 356:432 the β-O-linked-N-acetylglucosamine (O-GlcNAc) post-translational modification of proteins 356:444 In particular, diabetes can augment flux through accessory pathways of glucose metabolism, such as the hexosamine biosynthetic pathway (HBP), which produces the sugar donor for the β-O-linked-N-acetylglucosamine (O-GlcNAc) post-translational modification of proteins. 25627821 2 17 theme proteins 437:444 arg1 modification 421:432 the β-O-linked-N-acetylglucosamine (O-GlcNAc) post-translational modification 356:432 the β-O-linked-N-acetylglucosamine (O-GlcNAc) post-translational modification of proteins 356:444 In particular, diabetes can augment flux through accessory pathways of glucose metabolism, such as the hexosamine biosynthetic pathway (HBP), which produces the sugar donor for the β-O-linked-N-acetylglucosamine (O-GlcNAc) post-translational modification of proteins. 25627821 7 18 theme mitochondrial 1382:1394 arg1 metabolism 1396:1405 mitochondrial metabolism 1382:1405 mitochondrial metabolism (P<0.05) 1382:1414 Furthermore, an osmotic control recapitulated high-glucose-induced changes to mitochondrial metabolism (P<0.05) without increasing O-GlcNAcylation. 25627821 7 18 theme mitochondrial 1382:1394 arg1 P<0.05 1408:1413 P<0.05 1408:1413 P<0.05 1408:1413 Furthermore, an osmotic control recapitulated high-glucose-induced changes to mitochondrial metabolism (P<0.05) without increasing O-GlcNAcylation. 25627821 6 19 theme mitochondrial 1173:1185 arg1 respiration 1187:1197 mitochondrial respiration 1173:1197 mitochondrial respiration 1173:1197 Augmentation of O-GlcNAcylation with high glucose (33 mM) was associated with diminished basal and maximal cardiomyocyte respiration, a decreased mitochondrial reserve capacity and lower Complex II-dependent respiration (P<0.05); however, pharmacological or genetic modulation of O-GlcNAc modifications under normal or high glucose conditions showed few significant effects on mitochondrial respiration, suggesting that O-GlcNAc does not play a major role in regulating cardiomyocyte mitochondrial function. 25627821 6 20 theme major 1241:1245 arg1 role 1247:1250 a major role 1239:1250 a major role 1239:1250 Augmentation of O-GlcNAcylation with high glucose (33 mM) was associated with diminished basal and maximal cardiomyocyte respiration, a decreased mitochondrial reserve capacity and lower Complex II-dependent respiration (P<0.05); however, pharmacological or genetic modulation of O-GlcNAc modifications under normal or high glucose conditions showed few significant effects on mitochondrial respiration, suggesting that O-GlcNAc does not play a major role in regulating cardiomyocyte mitochondrial function. 25627821 6 21 theme O-GlcNAc 1076:1083 arg1 modifications 1085:1097 O-GlcNAc modifications 1076:1097 O-GlcNAc modifications 1076:1097 Augmentation of O-GlcNAcylation with high glucose (33 mM) was associated with diminished basal and maximal cardiomyocyte respiration, a decreased mitochondrial reserve capacity and lower Complex II-dependent respiration (P<0.05); however, pharmacological or genetic modulation of O-GlcNAc modifications under normal or high glucose conditions showed few significant effects on mitochondrial respiration, suggesting that O-GlcNAc does not play a major role in regulating cardiomyocyte mitochondrial function. 25627821 7 22 theme high-glucose-induced 1350:1369 arg1 changes 1371:1377 high-glucose-induced changes 1350:1377 high-glucose-induced changes to mitochondrial metabolism (P<0.05) 1350:1414 Furthermore, an osmotic control recapitulated high-glucose-induced changes to mitochondrial metabolism (P<0.05) without increasing O-GlcNAcylation. 25627821 6 23 theme normal 1105:1110 arg1 conditions 1128:1137 normal or high glucose conditions 1105:1137 normal or high glucose conditions 1105:1137 Augmentation of O-GlcNAcylation with high glucose (33 mM) was associated with diminished basal and maximal cardiomyocyte respiration, a decreased mitochondrial reserve capacity and lower Complex II-dependent respiration (P<0.05); however, pharmacological or genetic modulation of O-GlcNAc modifications under normal or high glucose conditions showed few significant effects on mitochondrial respiration, suggesting that O-GlcNAc does not play a major role in regulating cardiomyocyte mitochondrial function. 25627821 6 24 theme high 833:836 arg1 33 mM 847:851 33 mM 847:851 33 mM 847:851 Augmentation of O-GlcNAcylation with high glucose (33 mM) was associated with diminished basal and maximal cardiomyocyte respiration, a decreased mitochondrial reserve capacity and lower Complex II-dependent respiration (P<0.05); however, pharmacological or genetic modulation of O-GlcNAc modifications under normal or high glucose conditions showed few significant effects on mitochondrial respiration, suggesting that O-GlcNAc does not play a major role in regulating cardiomyocyte mitochondrial function. 25627821 6 24 theme high 833:836 arg1 glucose 838:844 high glucose 833:844 high glucose (33 mM) 833:852 Augmentation of O-GlcNAcylation with high glucose (33 mM) was associated with diminished basal and maximal cardiomyocyte respiration, a decreased mitochondrial reserve capacity and lower Complex II-dependent respiration (P<0.05); however, pharmacological or genetic modulation of O-GlcNAc modifications under normal or high glucose conditions showed few significant effects on mitochondrial respiration, suggesting that O-GlcNAc does not play a major role in regulating cardiomyocyte mitochondrial function. 25627821 3 25 theme mitochondrial 470:482 arg1 dysfunction 484:494 mitochondrial dysfunction 470:494 mitochondrial dysfunction 470:494 Diabetes also promotes mitochondrial dysfunction. 25627821 0 26 theme High 0:3 arg1 glucose 5:11 High glucose 0:11 High glucose 0:11 High glucose induces mitochondrial dysfunction independently of protein O-GlcNAcylation. 25627821 6 27 theme glucose 1120:1126 arg1 conditions 1128:1137 normal or high glucose conditions 1105:1137 normal or high glucose conditions 1105:1137 Augmentation of O-GlcNAcylation with high glucose (33 mM) was associated with diminished basal and maximal cardiomyocyte respiration, a decreased mitochondrial reserve capacity and lower Complex II-dependent respiration (P<0.05); however, pharmacological or genetic modulation of O-GlcNAc modifications under normal or high glucose conditions showed few significant effects on mitochondrial respiration, suggesting that O-GlcNAc does not play a major role in regulating cardiomyocyte mitochondrial function. 25627821 5 28 theme mitochondrial 745:757 arg1 function 759:766 mitochondrial function 745:766 mitochondrial function in isolated cardiomyocytes 745:793 In the present study, we tested whether high-glucose-induced increases in O-GlcNAc modifications directly regulate mitochondrial function in isolated cardiomyocytes. 25627821 1 29 from perturbations 137:149 arg1 metabolism 167:176 intermediary metabolism 154:176 intermediary metabolism 154:176 Diabetes is characterized by hyperglycaemia and perturbations in intermediary metabolism. 25627821 6 30 theme O-GlcNAcylation 812:826 arg1 Augmentation 796:807 Augmentation 796:807 Augmentation of O-GlcNAcylation with high glucose (33 mM) 796:852 Augmentation of O-GlcNAcylation with high glucose (33 mM) was associated with diminished basal and maximal cardiomyocyte respiration, a decreased mitochondrial reserve capacity and lower Complex II-dependent respiration (P<0.05); however, pharmacological or genetic modulation of O-GlcNAc modifications under normal or high glucose conditions showed few significant effects on mitochondrial respiration, suggesting that O-GlcNAc does not play a major role in regulating cardiomyocyte mitochondrial function. 25627821 2 31 theme post-translational 402:419 arg1 modification 421:432 the β-O-linked-N-acetylglucosamine (O-GlcNAc) post-translational modification 356:432 the β-O-linked-N-acetylglucosamine (O-GlcNAc) post-translational modification of proteins 356:444 In particular, diabetes can augment flux through accessory pathways of glucose metabolism, such as the hexosamine biosynthetic pathway (HBP), which produces the sugar donor for the β-O-linked-N-acetylglucosamine (O-GlcNAc) post-translational modification of proteins. 25627821 0 32 theme mitochondrial 21:33 arg1 dysfunction 35:45 mitochondrial dysfunction 21:45 mitochondrial dysfunction 21:45 High glucose induces mitochondrial dysfunction independently of protein O-GlcNAcylation. 25627821 6 33 theme cardiomyocyte 903:915 arg1 respiration 917:927 diminished basal and maximal cardiomyocyte respiration 874:927 diminished basal and maximal cardiomyocyte respiration 874:927 Augmentation of O-GlcNAcylation with high glucose (33 mM) was associated with diminished basal and maximal cardiomyocyte respiration, a decreased mitochondrial reserve capacity and lower Complex II-dependent respiration (P<0.05); however, pharmacological or genetic modulation of O-GlcNAc modifications under normal or high glucose conditions showed few significant effects on mitochondrial respiration, suggesting that O-GlcNAc does not play a major role in regulating cardiomyocyte mitochondrial function. 25627821 6 34 theme maximal 895:901 arg1 respiration 917:927 diminished basal and maximal cardiomyocyte respiration 874:927 diminished basal and maximal cardiomyocyte respiration 874:927 Augmentation of O-GlcNAcylation with high glucose (33 mM) was associated with diminished basal and maximal cardiomyocyte respiration, a decreased mitochondrial reserve capacity and lower Complex II-dependent respiration (P<0.05); however, pharmacological or genetic modulation of O-GlcNAc modifications under normal or high glucose conditions showed few significant effects on mitochondrial respiration, suggesting that O-GlcNAc does not play a major role in regulating cardiomyocyte mitochondrial function. 25627821 6 35 theme reserve 956:962 arg1 capacity 964:971 a decreased mitochondrial reserve capacity 930:971 a decreased mitochondrial reserve capacity 930:971 Augmentation of O-GlcNAcylation with high glucose (33 mM) was associated with diminished basal and maximal cardiomyocyte respiration, a decreased mitochondrial reserve capacity and lower Complex II-dependent respiration (P<0.05); however, pharmacological or genetic modulation of O-GlcNAc modifications under normal or high glucose conditions showed few significant effects on mitochondrial respiration, suggesting that O-GlcNAc does not play a major role in regulating cardiomyocyte mitochondrial function. 25627821 6 36 theme diminished 874:883 arg1 respiration 917:927 diminished basal and maximal cardiomyocyte respiration 874:927 diminished basal and maximal cardiomyocyte respiration 874:927 Augmentation of O-GlcNAcylation with high glucose (33 mM) was associated with diminished basal and maximal cardiomyocyte respiration, a decreased mitochondrial reserve capacity and lower Complex II-dependent respiration (P<0.05); however, pharmacological or genetic modulation of O-GlcNAc modifications under normal or high glucose conditions showed few significant effects on mitochondrial respiration, suggesting that O-GlcNAc does not play a major role in regulating cardiomyocyte mitochondrial function. 25627821 5 37 from increases 691:699 arg1 modifications 713:725 O-GlcNAc modifications 704:725 O-GlcNAc modifications 704:725 In the present study, we tested whether high-glucose-induced increases in O-GlcNAc modifications directly regulate mitochondrial function in isolated cardiomyocytes. 25627821 8 38 theme increased 1458:1466 arg1 O-GlcNAcylation 1468:1482 increased O-GlcNAcylation 1458:1482 increased O-GlcNAcylation 1458:1482 Thus, increased O-GlcNAcylation is neither sufficient nor necessary for high-glucose-induced suppression of mitochondrial metabolism in isolated cardiomyocytes. 25627821 4 39 dep diabetes 535:542 arg1 modifications 600:612 modifications 600:612 modifications 600:612 Nevertheless, the relationships among diabetes, hyperglycaemia, mitochondrial dysfunction and O-GlcNAc modifications remain unclear. 25627821 7 40 theme osmotic 1320:1326 arg1 control 1328:1334 an osmotic control 1317:1334 an osmotic control 1317:1334 Furthermore, an osmotic control recapitulated high-glucose-induced changes to mitochondrial metabolism (P<0.05) without increasing O-GlcNAcylation. 25627821 0 41 theme protein 64:70 arg1 O-GlcNAcylation 72:86 protein O-GlcNAcylation 64:86 protein O-GlcNAcylation 64:86 High glucose induces mitochondrial dysfunction independently of protein O-GlcNAcylation. 25627821 6 42 theme modifications 1085:1097 arg1 modulation 1062:1071 pharmacological or genetic modulation 1035:1071 pharmacological or genetic modulation of O-GlcNAc modifications under normal or high glucose conditions 1035:1137 Augmentation of O-GlcNAcylation with high glucose (33 mM) was associated with diminished basal and maximal cardiomyocyte respiration, a decreased mitochondrial reserve capacity and lower Complex II-dependent respiration (P<0.05); however, pharmacological or genetic modulation of O-GlcNAc modifications under normal or high glucose conditions showed few significant effects on mitochondrial respiration, suggesting that O-GlcNAc does not play a major role in regulating cardiomyocyte mitochondrial function. 25627821 6 43 with Augmentation 796:807 arg1 33 mM 847:851 33 mM 847:851 33 mM 847:851 Augmentation of O-GlcNAcylation with high glucose (33 mM) was associated with diminished basal and maximal cardiomyocyte respiration, a decreased mitochondrial reserve capacity and lower Complex II-dependent respiration (P<0.05); however, pharmacological or genetic modulation of O-GlcNAc modifications under normal or high glucose conditions showed few significant effects on mitochondrial respiration, suggesting that O-GlcNAc does not play a major role in regulating cardiomyocyte mitochondrial function. 25627821 6 43 with Augmentation 796:807 arg1 glucose 838:844 high glucose 833:844 high glucose (33 mM) 833:852 Augmentation of O-GlcNAcylation with high glucose (33 mM) was associated with diminished basal and maximal cardiomyocyte respiration, a decreased mitochondrial reserve capacity and lower Complex II-dependent respiration (P<0.05); however, pharmacological or genetic modulation of O-GlcNAc modifications under normal or high glucose conditions showed few significant effects on mitochondrial respiration, suggesting that O-GlcNAc does not play a major role in regulating cardiomyocyte mitochondrial function. 25627821 6 44 theme II-dependent 991:1002 arg1 respiration 1004:1014 lower Complex II-dependent respiration 977:1014 lower Complex II-dependent respiration (P<0.05) 977:1023 Augmentation of O-GlcNAcylation with high glucose (33 mM) was associated with diminished basal and maximal cardiomyocyte respiration, a decreased mitochondrial reserve capacity and lower Complex II-dependent respiration (P<0.05); however, pharmacological or genetic modulation of O-GlcNAc modifications under normal or high glucose conditions showed few significant effects on mitochondrial respiration, suggesting that O-GlcNAc does not play a major role in regulating cardiomyocyte mitochondrial function. 25627821 6 44 theme II-dependent 991:1002 arg1 P<0.05 1017:1022 P<0.05 1017:1022 P<0.05 1017:1022 Augmentation of O-GlcNAcylation with high glucose (33 mM) was associated with diminished basal and maximal cardiomyocyte respiration, a decreased mitochondrial reserve capacity and lower Complex II-dependent respiration (P<0.05); however, pharmacological or genetic modulation of O-GlcNAc modifications under normal or high glucose conditions showed few significant effects on mitochondrial respiration, suggesting that O-GlcNAc does not play a major role in regulating cardiomyocyte mitochondrial function. 25627821 2 45 theme metabolism 258:267 arg1 pathway 306:312 the hexosamine biosynthetic pathway 278:312 the hexosamine biosynthetic pathway (HBP) 278:318 In particular, diabetes can augment flux through accessory pathways of glucose metabolism, such as the hexosamine biosynthetic pathway (HBP), which produces the sugar donor for the β-O-linked-N-acetylglucosamine (O-GlcNAc) post-translational modification of proteins. 25627821 2 45 theme metabolism 258:267 arg1 pathways 238:245 accessory pathways 228:245 accessory pathways 228:245 In particular, diabetes can augment flux through accessory pathways of glucose metabolism, such as the hexosamine biosynthetic pathway (HBP), which produces the sugar donor for the β-O-linked-N-acetylglucosamine (O-GlcNAc) post-translational modification of proteins. 25627821 6 46 theme basal 885:889 arg1 respiration 917:927 diminished basal and maximal cardiomyocyte respiration 874:927 diminished basal and maximal cardiomyocyte respiration 874:927 Augmentation of O-GlcNAcylation with high glucose (33 mM) was associated with diminished basal and maximal cardiomyocyte respiration, a decreased mitochondrial reserve capacity and lower Complex II-dependent respiration (P<0.05); however, pharmacological or genetic modulation of O-GlcNAc modifications under normal or high glucose conditions showed few significant effects on mitochondrial respiration, suggesting that O-GlcNAc does not play a major role in regulating cardiomyocyte mitochondrial function. 25627821 8 47 theme high-glucose-induced 1524:1543 arg1 suppression 1545:1555 high-glucose-induced suppression 1524:1555 high-glucose-induced suppression of mitochondrial metabolism in isolated cardiomyocytes 1524:1610 Thus, increased O-GlcNAcylation is neither sufficient nor necessary for high-glucose-induced suppression of mitochondrial metabolism in isolated cardiomyocytes. 25627821 5 48 from function 759:766 arg1 cardiomyocytes 780:793 isolated cardiomyocytes 771:793 isolated cardiomyocytes 771:793 In the present study, we tested whether high-glucose-induced increases in O-GlcNAc modifications directly regulate mitochondrial function in isolated cardiomyocytes. 25627821 6 49 theme Complex 983:989 arg1 respiration 1004:1014 lower Complex II-dependent respiration 977:1014 lower Complex II-dependent respiration (P<0.05) 977:1023 Augmentation of O-GlcNAcylation with high glucose (33 mM) was associated with diminished basal and maximal cardiomyocyte respiration, a decreased mitochondrial reserve capacity and lower Complex II-dependent respiration (P<0.05); however, pharmacological or genetic modulation of O-GlcNAc modifications under normal or high glucose conditions showed few significant effects on mitochondrial respiration, suggesting that O-GlcNAc does not play a major role in regulating cardiomyocyte mitochondrial function. 25627821 6 49 theme Complex 983:989 arg1 P<0.05 1017:1022 P<0.05 1017:1022 P<0.05 1017:1022 Augmentation of O-GlcNAcylation with high glucose (33 mM) was associated with diminished basal and maximal cardiomyocyte respiration, a decreased mitochondrial reserve capacity and lower Complex II-dependent respiration (P<0.05); however, pharmacological or genetic modulation of O-GlcNAc modifications under normal or high glucose conditions showed few significant effects on mitochondrial respiration, suggesting that O-GlcNAc does not play a major role in regulating cardiomyocyte mitochondrial function. 25627821 2 50 theme glucose 250:256 arg1 metabolism 258:267 glucose metabolism 250:267 glucose metabolism 250:267 In particular, diabetes can augment flux through accessory pathways of glucose metabolism, such as the hexosamine biosynthetic pathway (HBP), which produces the sugar donor for the β-O-linked-N-acetylglucosamine (O-GlcNAc) post-translational modification of proteins. 25627821 5 51 theme present 637:643 arg1 study 645:649 the present study 633:649 the present study 633:649 In the present study, we tested whether high-glucose-induced increases in O-GlcNAc modifications directly regulate mitochondrial function in isolated cardiomyocytes. 25627821 1 52 from hyperglycaemia 118:131 arg1 metabolism 167:176 intermediary metabolism 154:176 intermediary metabolism 154:176 Diabetes is characterized by hyperglycaemia and perturbations in intermediary metabolism. 25627821 6 53 theme lower 977:981 arg1 respiration 1004:1014 lower Complex II-dependent respiration 977:1014 lower Complex II-dependent respiration (P<0.05) 977:1023 Augmentation of O-GlcNAcylation with high glucose (33 mM) was associated with diminished basal and maximal cardiomyocyte respiration, a decreased mitochondrial reserve capacity and lower Complex II-dependent respiration (P<0.05); however, pharmacological or genetic modulation of O-GlcNAc modifications under normal or high glucose conditions showed few significant effects on mitochondrial respiration, suggesting that O-GlcNAc does not play a major role in regulating cardiomyocyte mitochondrial function. 25627821 6 53 theme lower 977:981 arg1 P<0.05 1017:1022 P<0.05 1017:1022 P<0.05 1017:1022 Augmentation of O-GlcNAcylation with high glucose (33 mM) was associated with diminished basal and maximal cardiomyocyte respiration, a decreased mitochondrial reserve capacity and lower Complex II-dependent respiration (P<0.05); however, pharmacological or genetic modulation of O-GlcNAc modifications under normal or high glucose conditions showed few significant effects on mitochondrial respiration, suggesting that O-GlcNAc does not play a major role in regulating cardiomyocyte mitochondrial function. 25627821 2 54 theme biosynthetic 293:304 arg1 HBP 315:317 HBP 315:317 HBP 315:317 In particular, diabetes can augment flux through accessory pathways of glucose metabolism, such as the hexosamine biosynthetic pathway (HBP), which produces the sugar donor for the β-O-linked-N-acetylglucosamine (O-GlcNAc) post-translational modification of proteins. 25627821 2 54 theme biosynthetic 293:304 arg1 pathway 306:312 the hexosamine biosynthetic pathway 278:312 the hexosamine biosynthetic pathway (HBP) 278:318 In particular, diabetes can augment flux through accessory pathways of glucose metabolism, such as the hexosamine biosynthetic pathway (HBP), which produces the sugar donor for the β-O-linked-N-acetylglucosamine (O-GlcNAc) post-translational modification of proteins. 25627821 1 55 theme intermediary 154:165 arg1 metabolism 167:176 intermediary metabolism 154:176 intermediary metabolism 154:176 Diabetes is characterized by hyperglycaemia and perturbations in intermediary metabolism. 25627821 8 56 theme isolated 1588:1595 arg1 cardiomyocytes 1597:1610 isolated cardiomyocytes 1588:1610 isolated cardiomyocytes 1588:1610 Thus, increased O-GlcNAcylation is neither sufficient nor necessary for high-glucose-induced suppression of mitochondrial metabolism in isolated cardiomyocytes. 25627821 2 57 theme accessory 228:236 arg1 pathway 306:312 the hexosamine biosynthetic pathway 278:312 the hexosamine biosynthetic pathway (HBP) 278:318 In particular, diabetes can augment flux through accessory pathways of glucose metabolism, such as the hexosamine biosynthetic pathway (HBP), which produces the sugar donor for the β-O-linked-N-acetylglucosamine (O-GlcNAc) post-translational modification of proteins. 25627821 2 57 theme accessory 228:236 arg1 pathways 238:245 accessory pathways 228:245 accessory pathways 228:245 In particular, diabetes can augment flux through accessory pathways of glucose metabolism, such as the hexosamine biosynthetic pathway (HBP), which produces the sugar donor for the β-O-linked-N-acetylglucosamine (O-GlcNAc) post-translational modification of proteins. 25627821 2 58 theme hexosamine 282:291 arg1 HBP 315:317 HBP 315:317 HBP 315:317 In particular, diabetes can augment flux through accessory pathways of glucose metabolism, such as the hexosamine biosynthetic pathway (HBP), which produces the sugar donor for the β-O-linked-N-acetylglucosamine (O-GlcNAc) post-translational modification of proteins. 25627821 2 58 theme hexosamine 282:291 arg1 pathway 306:312 the hexosamine biosynthetic pathway 278:312 the hexosamine biosynthetic pathway (HBP) 278:318 In particular, diabetes can augment flux through accessory pathways of glucose metabolism, such as the hexosamine biosynthetic pathway (HBP), which produces the sugar donor for the β-O-linked-N-acetylglucosamine (O-GlcNAc) post-translational modification of proteins. 25627821 2 59 theme sugar 340:344 arg1 donor 346:350 the sugar donor 336:350 the sugar donor for the β-O-linked-N-acetylglucosamine (O-GlcNAc) post-translational modification of proteins 336:444 In particular, diabetes can augment flux through accessory pathways of glucose metabolism, such as the hexosamine biosynthetic pathway (HBP), which produces the sugar donor for the β-O-linked-N-acetylglucosamine (O-GlcNAc) post-translational modification of proteins. 25627821 6 60 dep associated 858:867 arg1 showed 1139:1144 showed 1139:1144 showed 1139:1144 Augmentation of O-GlcNAcylation with high glucose (33 mM) was associated with diminished basal and maximal cardiomyocyte respiration, a decreased mitochondrial reserve capacity and lower Complex II-dependent respiration (P<0.05); however, pharmacological or genetic modulation of O-GlcNAc modifications under normal or high glucose conditions showed few significant effects on mitochondrial respiration, suggesting that O-GlcNAc does not play a major role in regulating cardiomyocyte mitochondrial function. 25627821 6 61 theme mitochondrial 1280:1292 arg1 function 1294:1301 cardiomyocyte mitochondrial function 1266:1301 cardiomyocyte mitochondrial function 1266:1301 Augmentation of O-GlcNAcylation with high glucose (33 mM) was associated with diminished basal and maximal cardiomyocyte respiration, a decreased mitochondrial reserve capacity and lower Complex II-dependent respiration (P<0.05); however, pharmacological or genetic modulation of O-GlcNAc modifications under normal or high glucose conditions showed few significant effects on mitochondrial respiration, suggesting that O-GlcNAc does not play a major role in regulating cardiomyocyte mitochondrial function. 25627821 8 62 from suppression 1545:1555 arg1 cardiomyocytes 1597:1610 isolated cardiomyocytes 1588:1610 isolated cardiomyocytes 1588:1610 Thus, increased O-GlcNAcylation is neither sufficient nor necessary for high-glucose-induced suppression of mitochondrial metabolism in isolated cardiomyocytes. 25627821 2 63 theme O-GlcNAc 392:399 arg1 modification 421:432 the β-O-linked-N-acetylglucosamine (O-GlcNAc) post-translational modification 356:432 the β-O-linked-N-acetylglucosamine (O-GlcNAc) post-translational modification of proteins 356:444 In particular, diabetes can augment flux through accessory pathways of glucose metabolism, such as the hexosamine biosynthetic pathway (HBP), which produces the sugar donor for the β-O-linked-N-acetylglucosamine (O-GlcNAc) post-translational modification of proteins. 24506136 0 0 theme model 73:77 arg1 protein 85:91 a model f-box protein 71:91 a model f-box protein 71:91 Glycosylation of Skp1 affects its conformation and promotes binding to a model f-box protein. 24506136 8 1 theme F-box 1599:1603 arg1 site 1613:1616 the F-box binding site 1595:1616 the F-box binding site 1595:1616 Considering that regions of free Skp1 are intrinsically disordered and Skp1 can adopt distinct folds when bound to F-box proteins, we propose that glycosylation, which occurs adjacent to the F-box binding site, influences the spectrum of energetically similar conformations that vary inversely in their propensity to dock with Fbs1 or another Skp1. 24506136 6 2 theme apoprotein 1150:1159 arg1 envelopes 1105:1113 the molecular envelopes 1091:1113 the molecular envelopes of fully glycosylated Skp1 and the apoprotein 1091:1159 A comparison of the molecular envelopes of fully glycosylated Skp1 and the apoprotein indicated that both isoforms exist as an antiparallel dimer that is more compact and extended in the glycosylated state. 24506136 2 3 theme Skp1/cullin1/F-box 340:357 arg1 family 367:372 the Skp1/cullin1/F-box protein family 336:372 the Skp1/cullin1/F-box protein family of E3 ubiquitin ligases 336:396 Skp1 is an adapter in the Skp1/cullin1/F-box protein family of E3 ubiquitin ligases that targets specific proteins for polyubiquitination and subsequent proteasomal degradation. 24506136 6 4 theme envelopes 1105:1113 arg1 comparison 1077:1086 A comparison 1075:1086 A comparison of the molecular envelopes of fully glycosylated Skp1 and the apoprotein 1075:1159 A comparison of the molecular envelopes of fully glycosylated Skp1 and the apoprotein indicated that both isoforms exist as an antiparallel dimer that is more compact and extended in the glycosylated state. 24506136 5 5 theme increased 1012:1020 arg1 order 1030:1034 increased folding order 1012:1034 increased folding order 1012:1034 This difference correlated with the increased α-helical and decreased β-sheet content of glycosylated Skp1s based on circular dichroism and increased folding order based on small-angle X-ray scattering. 24506136 5 6 theme circular 989:996 arg1 dichroism 998:1006 circular dichroism 989:1006 circular dichroism 989:1006 This difference correlated with the increased α-helical and decreased β-sheet content of glycosylated Skp1s based on circular dichroism and increased folding order based on small-angle X-ray scattering. 24506136 3 7 theme glycosylation 539:551 arg1 consequences 523:534 the biochemical consequences 507:534 the biochemical consequences of glycosylation 507:551 To investigate the biochemical consequences of glycosylation, untagged full-length Skp1 and several of its posttranslationally modified isoforms were expressed and purified to near homogeneity using recombinant and in vitro strategies. 24506136 1 8 theme O-linked 239:246 arg1 pentasaccharide 248:262 an O-linked pentasaccharide 236:262 an O-linked pentasaccharide that contributes to O2 regulation of development 236:311 In the social amoeba Dictyostelium, Skp1 is hydroxylated on proline 143 and further modified by three cytosolic glycosyltransferases to yield an O-linked pentasaccharide that contributes to O2 regulation of development. 24506136 8 9 theme similar 1660:1666 arg1 conformations 1668:1680 energetically similar conformations 1646:1680 energetically similar conformations that vary inversely in their propensity to dock with Fbs1 or another Skp1 1646:1754 Considering that regions of free Skp1 are intrinsically disordered and Skp1 can adopt distinct folds when bound to F-box proteins, we propose that glycosylation, which occurs adjacent to the F-box binding site, influences the spectrum of energetically similar conformations that vary inversely in their propensity to dock with Fbs1 or another Skp1. 24506136 1 10 from hydroxylated 138:149 arg1 Dictyostelium 115:127 the social amoeba Dictyostelium 97:127 the social amoeba Dictyostelium 97:127 In the social amoeba Dictyostelium, Skp1 is hydroxylated on proline 143 and further modified by three cytosolic glycosyltransferases to yield an O-linked pentasaccharide that contributes to O2 regulation of development. 24506136 4 11 theme glycosylated 841:852 arg1 isoforms 854:861 the glycosylated isoforms 837:861 the glycosylated isoforms of Skp1 837:869 Interaction studies with the soluble mammalian F-box protein Fbs1/Fbg1/OCP1 revealed preferential binding to the glycosylated isoforms of Skp1. 24506136 0 12 theme f-box 79:83 arg1 protein 85:91 a model f-box protein 71:91 a model f-box protein 71:91 Glycosylation of Skp1 affects its conformation and promotes binding to a model f-box protein. 24506136 5 13 gly glycosylated 961:972 arg1 Skp1s 974:978 glycosylated Skp1s 961:978 glycosylated Skp1s based on circular dichroism and increased folding order based on small-angle X-ray scattering 961:1072 This difference correlated with the increased α-helical and decreased β-sheet content of glycosylated Skp1s based on circular dichroism and increased folding order based on small-angle X-ray scattering. 24506136 4 14 theme soluble 757:763 arg1 Fbs1/Fbg1/OCP1 789:802 the soluble mammalian F-box protein Fbs1/Fbg1/OCP1 753:802 the soluble mammalian F-box protein Fbs1/Fbg1/OCP1 753:802 Interaction studies with the soluble mammalian F-box protein Fbs1/Fbg1/OCP1 revealed preferential binding to the glycosylated isoforms of Skp1. 24506136 6 15 from state 1275:1279 arg1 dimer 1215:1219 an antiparallel dimer 1199:1219 an antiparallel dimer that is more compact and extended in the glycosylated state 1199:1279 A comparison of the molecular envelopes of fully glycosylated Skp1 and the apoprotein indicated that both isoforms exist as an antiparallel dimer that is more compact and extended in the glycosylated state. 24506136 6 15 from state 1275:1279 arg1 compact 1234:1240 compact 1234:1240 compact 1234:1240 A comparison of the molecular envelopes of fully glycosylated Skp1 and the apoprotein indicated that both isoforms exist as an antiparallel dimer that is more compact and extended in the glycosylated state. 24506136 4 16 theme protein 781:787 arg1 Fbs1/Fbg1/OCP1 789:802 the soluble mammalian F-box protein Fbs1/Fbg1/OCP1 753:802 the soluble mammalian F-box protein Fbs1/Fbg1/OCP1 753:802 Interaction studies with the soluble mammalian F-box protein Fbs1/Fbg1/OCP1 revealed preferential binding to the glycosylated isoforms of Skp1. 24506136 7 17 theme gel 1293:1295 arg1 filtration 1297:1306 Analytical gel filtration 1282:1306 Analytical gel filtration 1282:1306 Analytical gel filtration and chemical cross-linking studies showed a growing tendency of less modified isoforms to dimerize. 24506136 4 18 theme F-box 775:779 arg1 Fbs1/Fbg1/OCP1 789:802 the soluble mammalian F-box protein Fbs1/Fbg1/OCP1 753:802 the soluble mammalian F-box protein Fbs1/Fbg1/OCP1 753:802 Interaction studies with the soluble mammalian F-box protein Fbs1/Fbg1/OCP1 revealed preferential binding to the glycosylated isoforms of Skp1. 24506136 2 19 from adapter 325:331 arg1 family 367:372 the Skp1/cullin1/F-box protein family 336:372 the Skp1/cullin1/F-box protein family of E3 ubiquitin ligases 336:396 Skp1 is an adapter in the Skp1/cullin1/F-box protein family of E3 ubiquitin ligases that targets specific proteins for polyubiquitination and subsequent proteasomal degradation. 24506136 3 20 theme full-length 563:573 arg1 Skp1 575:578 untagged full-length Skp1 554:578 untagged full-length Skp1 554:578 To investigate the biochemical consequences of glycosylation, untagged full-length Skp1 and several of its posttranslationally modified isoforms were expressed and purified to near homogeneity using recombinant and in vitro strategies. 24506136 4 21 theme Interaction 728:738 arg1 studies 740:746 Interaction studies 728:746 Interaction studies with the soluble mammalian F-box protein Fbs1/Fbg1/OCP1 728:802 Interaction studies with the soluble mammalian F-box protein Fbs1/Fbg1/OCP1 revealed preferential binding to the glycosylated isoforms of Skp1. 24506136 2 22 theme ligases 390:396 arg1 family 367:372 the Skp1/cullin1/F-box protein family 336:372 the Skp1/cullin1/F-box protein family of E3 ubiquitin ligases 336:396 Skp1 is an adapter in the Skp1/cullin1/F-box protein family of E3 ubiquitin ligases that targets specific proteins for polyubiquitination and subsequent proteasomal degradation. 24506136 9 23 theme Skp1 1790:1793 arg1 function 1795:1802 Skp1 function 1790:1802 Skp1 function 1790:1802 Glycosylation may thus influence Skp1 function by modulating F-box protein binding in cells. 24506136 6 24 theme glycosylated 1124:1135 arg1 Skp1 1137:1140 fully glycosylated Skp1 1118:1140 fully glycosylated Skp1 1118:1140 A comparison of the molecular envelopes of fully glycosylated Skp1 and the apoprotein indicated that both isoforms exist as an antiparallel dimer that is more compact and extended in the glycosylated state. 24506136 2 25 theme ubiquitin 380:388 arg1 ligases 390:396 E3 ubiquitin ligases 377:396 E3 ubiquitin ligases 377:396 Skp1 is an adapter in the Skp1/cullin1/F-box protein family of E3 ubiquitin ligases that targets specific proteins for polyubiquitination and subsequent proteasomal degradation. 24506136 2 26 theme subsequent 456:465 arg1 degradation 479:489 subsequent proteasomal degradation 456:489 subsequent proteasomal degradation 456:489 Skp1 is an adapter in the Skp1/cullin1/F-box protein family of E3 ubiquitin ligases that targets specific proteins for polyubiquitination and subsequent proteasomal degradation. 24506136 4 27 with studies 740:746 arg1 Fbs1/Fbg1/OCP1 789:802 the soluble mammalian F-box protein Fbs1/Fbg1/OCP1 753:802 the soluble mammalian F-box protein Fbs1/Fbg1/OCP1 753:802 Interaction studies with the soluble mammalian F-box protein Fbs1/Fbg1/OCP1 revealed preferential binding to the glycosylated isoforms of Skp1. 24506136 1 28 from Dictyostelium 115:127 arg1 hydroxylated 138:149 hydroxylated 138:149 hydroxylated 138:149 In the social amoeba Dictyostelium, Skp1 is hydroxylated on proline 143 and further modified by three cytosolic glycosyltransferases to yield an O-linked pentasaccharide that contributes to O2 regulation of development. 24506136 4 29 theme preferential 813:824 arg1 binding 826:832 preferential binding 813:832 preferential binding to the glycosylated isoforms of Skp1 813:869 Interaction studies with the soluble mammalian F-box protein Fbs1/Fbg1/OCP1 revealed preferential binding to the glycosylated isoforms of Skp1. 24506136 7 30 theme isoforms 1386:1393 arg1 tendency 1360:1367 a growing tendency 1350:1367 a growing tendency of less modified isoforms to dimerize 1350:1405 Analytical gel filtration and chemical cross-linking studies showed a growing tendency of less modified isoforms to dimerize. 24506136 2 31 theme E3 377:378 arg1 ligases 390:396 E3 ubiquitin ligases 377:396 E3 ubiquitin ligases 377:396 Skp1 is an adapter in the Skp1/cullin1/F-box protein family of E3 ubiquitin ligases that targets specific proteins for polyubiquitination and subsequent proteasomal degradation. 24506136 7 32 theme Analytical 1282:1291 arg1 filtration 1297:1306 Analytical gel filtration 1282:1306 Analytical gel filtration 1282:1306 Analytical gel filtration and chemical cross-linking studies showed a growing tendency of less modified isoforms to dimerize. 24506136 8 33 theme conformations 1668:1680 arg1 spectrum 1634:1641 the spectrum 1630:1641 the spectrum of energetically similar conformations that vary inversely in their propensity to dock with Fbs1 or another Skp1 1630:1754 Considering that regions of free Skp1 are intrinsically disordered and Skp1 can adopt distinct folds when bound to F-box proteins, we propose that glycosylation, which occurs adjacent to the F-box binding site, influences the spectrum of energetically similar conformations that vary inversely in their propensity to dock with Fbs1 or another Skp1. 24506136 3 34 theme modified 619:626 arg1 isoforms 628:635 its posttranslationally modified isoforms 595:635 its posttranslationally modified isoforms 595:635 To investigate the biochemical consequences of glycosylation, untagged full-length Skp1 and several of its posttranslationally modified isoforms were expressed and purified to near homogeneity using recombinant and in vitro strategies. 24506136 5 35 theme Skp1s 974:978 arg1 content 950:956 β-sheet content 942:956 β-sheet content of glycosylated Skp1s based on circular dichroism and increased folding order based on small-angle X-ray scattering 942:1072 This difference correlated with the increased α-helical and decreased β-sheet content of glycosylated Skp1s based on circular dichroism and increased folding order based on small-angle X-ray scattering. 24506136 7 36 theme chemical 1312:1319 arg1 cross-linking 1321:1333 chemical cross-linking 1312:1333 chemical cross-linking 1312:1333 Analytical gel filtration and chemical cross-linking studies showed a growing tendency of less modified isoforms to dimerize. 24506136 1 37 link O-linked 239:246 arg1 pentasaccharide 248:262 an O-linked pentasaccharide 236:262 an O-linked pentasaccharide that contributes to O2 regulation of development 236:311 In the social amoeba Dictyostelium, Skp1 is hydroxylated on proline 143 and further modified by three cytosolic glycosyltransferases to yield an O-linked pentasaccharide that contributes to O2 regulation of development. 24506136 5 38 theme small-angle 1045:1055 arg1 scattering 1063:1072 small-angle X-ray scattering 1045:1072 small-angle X-ray scattering 1045:1072 This difference correlated with the increased α-helical and decreased β-sheet content of glycosylated Skp1s based on circular dichroism and increased folding order based on small-angle X-ray scattering. 24506136 0 39 theme Skp1 17:20 arg1 Glycosylation 0:12 Glycosylation 0:12 Glycosylation of Skp1 0:20 Glycosylation of Skp1 affects its conformation and promotes binding to a model f-box protein. 24506136 9 40 theme F-box 1818:1822 arg1 binding 1832:1838 F-box protein binding 1818:1838 F-box protein binding in cells 1818:1847 Glycosylation may thus influence Skp1 function by modulating F-box protein binding in cells. 24506136 5 41 theme X-ray 1057:1061 arg1 scattering 1063:1072 small-angle X-ray scattering 1045:1072 small-angle X-ray scattering 1045:1072 This difference correlated with the increased α-helical and decreased β-sheet content of glycosylated Skp1s based on circular dichroism and increased folding order based on small-angle X-ray scattering. 24506136 2 42 theme specific 411:418 arg1 proteins 420:427 specific proteins 411:427 specific proteins 411:427 Skp1 is an adapter in the Skp1/cullin1/F-box protein family of E3 ubiquitin ligases that targets specific proteins for polyubiquitination and subsequent proteasomal degradation. 24506136 4 43 theme mammalian 765:773 arg1 Fbs1/Fbg1/OCP1 789:802 the soluble mammalian F-box protein Fbs1/Fbg1/OCP1 753:802 the soluble mammalian F-box protein Fbs1/Fbg1/OCP1 753:802 Interaction studies with the soluble mammalian F-box protein Fbs1/Fbg1/OCP1 revealed preferential binding to the glycosylated isoforms of Skp1. 24506136 9 44 theme protein 1824:1830 arg1 binding 1832:1838 F-box protein binding 1818:1838 F-box protein binding in cells 1818:1847 Glycosylation may thus influence Skp1 function by modulating F-box protein binding in cells. 24506136 0 45 gly Glycosylation 0:12 arg1 Skp1 17:20 Skp1 17:20 Skp1 17:20 Glycosylation of Skp1 affects its conformation and promotes binding to a model f-box protein. 24506136 6 46 theme Skp1 1137:1140 arg1 envelopes 1105:1113 the molecular envelopes 1091:1113 the molecular envelopes of fully glycosylated Skp1 and the apoprotein 1091:1159 A comparison of the molecular envelopes of fully glycosylated Skp1 and the apoprotein indicated that both isoforms exist as an antiparallel dimer that is more compact and extended in the glycosylated state. 24506136 5 47 theme glycosylated 961:972 arg1 Skp1s 974:978 glycosylated Skp1s 961:978 glycosylated Skp1s based on circular dichroism and increased folding order based on small-angle X-ray scattering 961:1072 This difference correlated with the increased α-helical and decreased β-sheet content of glycosylated Skp1s based on circular dichroism and increased folding order based on small-angle X-ray scattering. 24506136 6 48 theme molecular 1095:1103 arg1 envelopes 1105:1113 the molecular envelopes 1091:1113 the molecular envelopes of fully glycosylated Skp1 and the apoprotein 1091:1159 A comparison of the molecular envelopes of fully glycosylated Skp1 and the apoprotein indicated that both isoforms exist as an antiparallel dimer that is more compact and extended in the glycosylated state. 24506136 5 49 theme β-sheet 942:948 arg1 content 950:956 β-sheet content 942:956 β-sheet content of glycosylated Skp1s based on circular dichroism and increased folding order based on small-angle X-ray scattering 942:1072 This difference correlated with the increased α-helical and decreased β-sheet content of glycosylated Skp1s based on circular dichroism and increased folding order based on small-angle X-ray scattering. 24506136 6 50 gly glycosylated 1262:1273 arg1 state 1275:1279 the glycosylated state 1258:1279 the glycosylated state 1258:1279 A comparison of the molecular envelopes of fully glycosylated Skp1 and the apoprotein indicated that both isoforms exist as an antiparallel dimer that is more compact and extended in the glycosylated state. 24506136 1 51 theme development 301:311 arg1 regulation 287:296 O2 regulation 284:296 O2 regulation of development 284:311 In the social amoeba Dictyostelium, Skp1 is hydroxylated on proline 143 and further modified by three cytosolic glycosyltransferases to yield an O-linked pentasaccharide that contributes to O2 regulation of development. 24506136 9 52 from binding 1832:1838 arg1 cells 1843:1847 cells 1843:1847 cells 1843:1847 Glycosylation may thus influence Skp1 function by modulating F-box protein binding in cells. 24506136 3 53 theme isoforms 628:635 arg1 Skp1 575:578 untagged full-length Skp1 554:578 untagged full-length Skp1 554:578 To investigate the biochemical consequences of glycosylation, untagged full-length Skp1 and several of its posttranslationally modified isoforms were expressed and purified to near homogeneity using recombinant and in vitro strategies. 24506136 3 54 theme biochemical 511:521 arg1 consequences 523:534 the biochemical consequences 507:534 the biochemical consequences of glycosylation 507:551 To investigate the biochemical consequences of glycosylation, untagged full-length Skp1 and several of its posttranslationally modified isoforms were expressed and purified to near homogeneity using recombinant and in vitro strategies. 24506136 2 55 theme proteasomal 467:477 arg1 degradation 479:489 subsequent proteasomal degradation 456:489 subsequent proteasomal degradation 456:489 Skp1 is an adapter in the Skp1/cullin1/F-box protein family of E3 ubiquitin ligases that targets specific proteins for polyubiquitination and subsequent proteasomal degradation. 24506136 8 56 theme F-box 1523:1527 arg1 proteins 1529:1536 F-box proteins 1523:1536 F-box proteins 1523:1536 Considering that regions of free Skp1 are intrinsically disordered and Skp1 can adopt distinct folds when bound to F-box proteins, we propose that glycosylation, which occurs adjacent to the F-box binding site, influences the spectrum of energetically similar conformations that vary inversely in their propensity to dock with Fbs1 or another Skp1. 24506136 7 57 dep filtration 1297:1306 arg1 studies 1335:1341 studies 1335:1341 studies 1335:1341 Analytical gel filtration and chemical cross-linking studies showed a growing tendency of less modified isoforms to dimerize. 24506136 8 58 theme Skp1 1441:1444 arg1 regions 1425:1431 regions 1425:1431 regions of free Skp1 1425:1444 Considering that regions of free Skp1 are intrinsically disordered and Skp1 can adopt distinct folds when bound to F-box proteins, we propose that glycosylation, which occurs adjacent to the F-box binding site, influences the spectrum of energetically similar conformations that vary inversely in their propensity to dock with Fbs1 or another Skp1. 24506136 6 59 from compact 1234:1240 arg1 state 1275:1279 the glycosylated state 1258:1279 the glycosylated state 1258:1279 A comparison of the molecular envelopes of fully glycosylated Skp1 and the apoprotein indicated that both isoforms exist as an antiparallel dimer that is more compact and extended in the glycosylated state. 24506136 1 60 theme social 101:106 arg1 Dictyostelium 115:127 the social amoeba Dictyostelium 97:127 the social amoeba Dictyostelium 97:127 In the social amoeba Dictyostelium, Skp1 is hydroxylated on proline 143 and further modified by three cytosolic glycosyltransferases to yield an O-linked pentasaccharide that contributes to O2 regulation of development. 24506136 7 61 theme less 1372:1375 arg1 isoforms 1386:1393 less modified isoforms 1372:1393 less modified isoforms 1372:1393 Analytical gel filtration and chemical cross-linking studies showed a growing tendency of less modified isoforms to dimerize. 24506136 3 62 theme near 668:671 arg1 homogeneity 673:683 near homogeneity 668:683 near homogeneity using recombinant and in vitro strategies 668:725 To investigate the biochemical consequences of glycosylation, untagged full-length Skp1 and several of its posttranslationally modified isoforms were expressed and purified to near homogeneity using recombinant and in vitro strategies. 24506136 1 63 theme amoeba 108:113 arg1 Dictyostelium 115:127 the social amoeba Dictyostelium 97:127 the social amoeba Dictyostelium 97:127 In the social amoeba Dictyostelium, Skp1 is hydroxylated on proline 143 and further modified by three cytosolic glycosyltransferases to yield an O-linked pentasaccharide that contributes to O2 regulation of development. 24506136 1 64 theme cytosolic 196:204 arg1 glycosyltransferases 206:225 three cytosolic glycosyltransferases 190:225 three cytosolic glycosyltransferases 190:225 In the social amoeba Dictyostelium, Skp1 is hydroxylated on proline 143 and further modified by three cytosolic glycosyltransferases to yield an O-linked pentasaccharide that contributes to O2 regulation of development. 24506136 5 65 theme folding 1022:1028 arg1 order 1030:1034 increased folding order 1012:1034 increased folding order 1012:1034 This difference correlated with the increased α-helical and decreased β-sheet content of glycosylated Skp1s based on circular dichroism and increased folding order based on small-angle X-ray scattering. 24506136 4 66 theme Skp1 866:869 arg1 isoforms 854:861 the glycosylated isoforms 837:861 the glycosylated isoforms of Skp1 837:869 Interaction studies with the soluble mammalian F-box protein Fbs1/Fbg1/OCP1 revealed preferential binding to the glycosylated isoforms of Skp1. 24506136 6 67 gly glycosylated 1124:1135 arg1 Skp1 1137:1140 fully glycosylated Skp1 1118:1140 fully glycosylated Skp1 1118:1140 A comparison of the molecular envelopes of fully glycosylated Skp1 and the apoprotein indicated that both isoforms exist as an antiparallel dimer that is more compact and extended in the glycosylated state. 24506136 3 68 theme untagged 554:561 arg1 Skp1 575:578 untagged full-length Skp1 554:578 untagged full-length Skp1 554:578 To investigate the biochemical consequences of glycosylation, untagged full-length Skp1 and several of its posttranslationally modified isoforms were expressed and purified to near homogeneity using recombinant and in vitro strategies. 24506136 3 69 dep recombinant 691:701 arg1 strategies 716:725 strategies 716:725 strategies 716:725 To investigate the biochemical consequences of glycosylation, untagged full-length Skp1 and several of its posttranslationally modified isoforms were expressed and purified to near homogeneity using recombinant and in vitro strategies. 24506136 6 70 theme antiparallel 1202:1213 arg1 dimer 1215:1219 an antiparallel dimer 1199:1219 an antiparallel dimer that is more compact and extended in the glycosylated state 1199:1279 A comparison of the molecular envelopes of fully glycosylated Skp1 and the apoprotein indicated that both isoforms exist as an antiparallel dimer that is more compact and extended in the glycosylated state. 24506136 6 70 theme antiparallel 1202:1213 arg1 compact 1234:1240 compact 1234:1240 compact 1234:1240 A comparison of the molecular envelopes of fully glycosylated Skp1 and the apoprotein indicated that both isoforms exist as an antiparallel dimer that is more compact and extended in the glycosylated state. 24506136 6 71 theme glycosylated 1262:1273 arg1 state 1275:1279 the glycosylated state 1258:1279 the glycosylated state 1258:1279 A comparison of the molecular envelopes of fully glycosylated Skp1 and the apoprotein indicated that both isoforms exist as an antiparallel dimer that is more compact and extended in the glycosylated state. 24506136 8 72 theme free 1436:1439 arg1 Skp1 1441:1444 free Skp1 1436:1444 free Skp1 1436:1444 Considering that regions of free Skp1 are intrinsically disordered and Skp1 can adopt distinct folds when bound to F-box proteins, we propose that glycosylation, which occurs adjacent to the F-box binding site, influences the spectrum of energetically similar conformations that vary inversely in their propensity to dock with Fbs1 or another Skp1. 24506136 8 73 dep distinct 1494:1501 arg1 folds 1503:1507 folds 1503:1507 folds 1503:1507 Considering that regions of free Skp1 are intrinsically disordered and Skp1 can adopt distinct folds when bound to F-box proteins, we propose that glycosylation, which occurs adjacent to the F-box binding site, influences the spectrum of energetically similar conformations that vary inversely in their propensity to dock with Fbs1 or another Skp1. 24506136 4 74 gly glycosylated 841:852 arg1 Skp1 866:869 Skp1 866:869 Skp1 866:869 Interaction studies with the soluble mammalian F-box protein Fbs1/Fbg1/OCP1 revealed preferential binding to the glycosylated isoforms of Skp1. 24506136 4 74 gly glycosylated 841:852 arg1 isoforms 854:861 the glycosylated isoforms 837:861 the glycosylated isoforms of Skp1 837:869 Interaction studies with the soluble mammalian F-box protein Fbs1/Fbg1/OCP1 revealed preferential binding to the glycosylated isoforms of Skp1. 24506136 8 75 theme binding 1605:1611 arg1 site 1613:1616 the F-box binding site 1595:1616 the F-box binding site 1595:1616 Considering that regions of free Skp1 are intrinsically disordered and Skp1 can adopt distinct folds when bound to F-box proteins, we propose that glycosylation, which occurs adjacent to the F-box binding site, influences the spectrum of energetically similar conformations that vary inversely in their propensity to dock with Fbs1 or another Skp1. 24506136 5 76 theme increased 908:916 arg1 α-helical 918:926 the increased α-helical 904:926 the increased α-helical 904:926 This difference correlated with the increased α-helical and decreased β-sheet content of glycosylated Skp1s based on circular dichroism and increased folding order based on small-angle X-ray scattering. 24506136 7 77 theme modified 1377:1384 arg1 isoforms 1386:1393 less modified isoforms 1372:1393 less modified isoforms 1372:1393 Analytical gel filtration and chemical cross-linking studies showed a growing tendency of less modified isoforms to dimerize. 24506136 2 78 theme protein 359:365 arg1 family 367:372 the Skp1/cullin1/F-box protein family 336:372 the Skp1/cullin1/F-box protein family of E3 ubiquitin ligases 336:396 Skp1 is an adapter in the Skp1/cullin1/F-box protein family of E3 ubiquitin ligases that targets specific proteins for polyubiquitination and subsequent proteasomal degradation. 24506136 7 79 theme growing 1352:1358 arg1 tendency 1360:1367 a growing tendency 1350:1367 a growing tendency of less modified isoforms to dimerize 1350:1405 Analytical gel filtration and chemical cross-linking studies showed a growing tendency of less modified isoforms to dimerize. 24506136 3 80 dep in 707:708 arg1 vitro 710:714 vitro 710:714 vitro 710:714 To investigate the biochemical consequences of glycosylation, untagged full-length Skp1 and several of its posttranslationally modified isoforms were expressed and purified to near homogeneity using recombinant and in vitro strategies. 24381264 5 0 from O-GlcNAcylation 902:916 arg1 slices 952:957 Sprague Dawley rat hippocampal slices 921:957 Sprague Dawley rat hippocampal slices 921:957 We report that acutely increasing O-GlcNAcylation in Sprague Dawley rat hippocampal slices induces an NMDA receptor and protein kinase C-independent long-term depression (LTD) at hippocampal CA3-CA1 synapses (O-GcNAc LTD). 24381264 1 1 theme receptor 151:158 arg1 subunits 168:175 AMPA receptor (AMPAR) subunits GluA1 and GluA2 146:191 AMPA receptor (AMPAR) subunits GluA1 and GluA2 146:191 Serine phosphorylation of AMPA receptor (AMPAR) subunits GluA1 and GluA2 modulates AMPAR trafficking during long-term changes in strength of hippocampal excitatory transmission required for normal learning and memory. 24381264 1 1 theme receptor 151:158 arg1 GluA2 187:191 GluA2 187:191 GluA2 187:191 Serine phosphorylation of AMPA receptor (AMPAR) subunits GluA1 and GluA2 modulates AMPAR trafficking during long-term changes in strength of hippocampal excitatory transmission required for normal learning and memory. 24381264 1 1 theme receptor 151:158 arg1 GluA1 177:181 GluA1 177:181 GluA1 177:181 Serine phosphorylation of AMPA receptor (AMPAR) subunits GluA1 and GluA2 modulates AMPAR trafficking during long-term changes in strength of hippocampal excitatory transmission required for normal learning and memory. 24381264 7 2 theme Increasing 1172:1181 arg1 O-GlcNAcylation 1183:1197 Increasing O-GlcNAcylation 1172:1197 Increasing O-GlcNAcylation 1172:1197 Increasing O-GlcNAcylation interferes with long-term potentiation, and in hippocampal behavioral assays, it prevents novel object recognition and placement without affecting contextual fear conditioning. 24381264 5 3 theme hippocampal 940:950 arg1 slices 952:957 Sprague Dawley rat hippocampal slices 921:957 Sprague Dawley rat hippocampal slices 921:957 We report that acutely increasing O-GlcNAcylation in Sprague Dawley rat hippocampal slices induces an NMDA receptor and protein kinase C-independent long-term depression (LTD) at hippocampal CA3-CA1 synapses (O-GcNAc LTD). 24381264 7 4 theme contextual 1346:1355 arg1 conditioning 1362:1373 contextual fear conditioning 1346:1373 contextual fear conditioning 1346:1373 Increasing O-GlcNAcylation interferes with long-term potentiation, and in hippocampal behavioral assays, it prevents novel object recognition and placement without affecting contextual fear conditioning. 24381264 0 5 theme depression 84:93 arg1 form 66:69 a novel form 58:69 a novel form of long-term depression at hippocampal synapses 58:117 O-GlcNAcylation of AMPA receptor GluA2 is associated with a novel form of long-term depression at hippocampal synapses. 24381264 8 6 theme altered 1521:1527 arg1 levels 1538:1543 altered O-GlcNAc levels 1521:1543 altered O-GlcNAc levels 1521:1543 Our findings provide evidence that O-GlcNAcylation dynamically modulates hippocampal synaptic function and learning and memory, and suggest that altered O-GlcNAc levels could underlie cognitive dysfunction in neurological diseases. 24381264 8 7 theme hippocampal 1449:1459 arg1 function 1470:1477 hippocampal synaptic function 1449:1477 hippocampal synaptic function 1449:1477 Our findings provide evidence that O-GlcNAcylation dynamically modulates hippocampal synaptic function and learning and memory, and suggest that altered O-GlcNAc levels could underlie cognitive dysfunction in neurological diseases. 24381264 5 8 theme rat 936:938 arg1 slices 952:957 Sprague Dawley rat hippocampal slices 921:957 Sprague Dawley rat hippocampal slices 921:957 We report that acutely increasing O-GlcNAcylation in Sprague Dawley rat hippocampal slices induces an NMDA receptor and protein kinase C-independent long-term depression (LTD) at hippocampal CA3-CA1 synapses (O-GcNAc LTD). 24381264 5 9 theme long-term 1017:1025 arg1 depression 1027:1036 long-term depression 1017:1036 protein kinase C-independent long-term depression (LTD) at hippocampal CA3-CA1 synapses (O-GcNAc LTD) 988:1088 We report that acutely increasing O-GlcNAcylation in Sprague Dawley rat hippocampal slices induces an NMDA receptor and protein kinase C-independent long-term depression (LTD) at hippocampal CA3-CA1 synapses (O-GcNAc LTD). 24381264 5 9 theme long-term 1017:1025 arg1 LTD 1039:1041 LTD 1039:1041 LTD 1039:1041 We report that acutely increasing O-GlcNAcylation in Sprague Dawley rat hippocampal slices induces an NMDA receptor and protein kinase C-independent long-term depression (LTD) at hippocampal CA3-CA1 synapses (O-GcNAc LTD). 24381264 5 9 theme long-term 1017:1025 arg1 LTD 1085:1087 LTD 1085:1087 LTD 1085:1087 We report that acutely increasing O-GlcNAcylation in Sprague Dawley rat hippocampal slices induces an NMDA receptor and protein kinase C-independent long-term depression (LTD) at hippocampal CA3-CA1 synapses (O-GcNAc LTD). 24381264 0 10 theme long-term 74:82 arg1 depression 84:93 long-term depression 74:93 long-term depression at hippocampal synapses 74:117 O-GlcNAcylation of AMPA receptor GluA2 is associated with a novel form of long-term depression at hippocampal synapses. 24381264 4 11 theme brain 781:785 arg1 function 787:794 brain function 781:794 brain function as phosphorylation 781:813 Furthermore, because key synaptic proteins are O-GlcNAcylated, this modification may be as important to brain function as phosphorylation, yet its physiological significance remains unknown. 24381264 3 12 theme O-GlcNAc 514:521 arg1 transferase 523:533 O-GlcNAc transferase 514:533 O-GlcNAc transferase (OGT) 514:539 This, together with the high expression of the enzymes O-GlcNAc transferase (OGT) and β-N-acetylglucosamindase (O-GlcNAcase), suggests a potential role for O-GlcNAcylation in modifying synaptic efficacy and cognition. 24381264 3 12 theme O-GlcNAc 514:521 arg1 enzymes 506:512 the enzymes 502:512 the enzymes O-GlcNAc transferase (OGT) and β-N-acetylglucosamindase (O-GlcNAcase) 502:582 This, together with the high expression of the enzymes O-GlcNAc transferase (OGT) and β-N-acetylglucosamindase (O-GlcNAcase), suggests a potential role for O-GlcNAcylation in modifying synaptic efficacy and cognition. 24381264 3 12 theme O-GlcNAc 514:521 arg1 OGT 536:538 OGT 536:538 OGT 536:538 This, together with the high expression of the enzymes O-GlcNAc transferase (OGT) and β-N-acetylglucosamindase (O-GlcNAcase), suggests a potential role for O-GlcNAcylation in modifying synaptic efficacy and cognition. 24381264 1 13 theme hippocampal 261:271 arg1 transmission 284:295 hippocampal excitatory transmission 261:295 hippocampal excitatory transmission required for normal learning and memory 261:335 Serine phosphorylation of AMPA receptor (AMPAR) subunits GluA1 and GluA2 modulates AMPAR trafficking during long-term changes in strength of hippocampal excitatory transmission required for normal learning and memory. 24381264 0 14 theme hippocampal 98:108 arg1 synapses 110:117 hippocampal synapses 98:117 hippocampal synapses 98:117 O-GlcNAcylation of AMPA receptor GluA2 is associated with a novel form of long-term depression at hippocampal synapses. 24381264 4 15 theme key 698:700 arg1 proteins 711:718 key synaptic proteins 698:718 key synaptic proteins 698:718 Furthermore, because key synaptic proteins are O-GlcNAcylated, this modification may be as important to brain function as phosphorylation, yet its physiological significance remains unknown. 24381264 1 16 theme AMPAR 161:165 arg1 subunits 168:175 AMPA receptor (AMPAR) subunits GluA1 and GluA2 146:191 AMPA receptor (AMPAR) subunits GluA1 and GluA2 146:191 Serine phosphorylation of AMPA receptor (AMPAR) subunits GluA1 and GluA2 modulates AMPAR trafficking during long-term changes in strength of hippocampal excitatory transmission required for normal learning and memory. 24381264 1 16 theme AMPAR 161:165 arg1 GluA2 187:191 GluA2 187:191 GluA2 187:191 Serine phosphorylation of AMPA receptor (AMPAR) subunits GluA1 and GluA2 modulates AMPAR trafficking during long-term changes in strength of hippocampal excitatory transmission required for normal learning and memory. 24381264 1 16 theme AMPAR 161:165 arg1 GluA1 177:181 GluA1 177:181 GluA1 177:181 Serine phosphorylation of AMPA receptor (AMPAR) subunits GluA1 and GluA2 modulates AMPAR trafficking during long-term changes in strength of hippocampal excitatory transmission required for normal learning and memory. 24381264 4 17 dep important 768:776 arg1 O-GlcNAcylated 724:737 O-GlcNAcylated 724:737 O-GlcNAcylated 724:737 Furthermore, because key synaptic proteins are O-GlcNAcylated, this modification may be as important to brain function as phosphorylation, yet its physiological significance remains unknown. 24381264 2 18 link O-linked 385:392 arg1 O-GlcNAc 417:424 O-GlcNAc 417:424 O-GlcNAc 417:424 The post-translational addition and removal of O-linked β-N-acetylglucosamine (O-GlcNAc) also occurs on serine residues. 24381264 2 18 link O-linked 385:392 arg1 β-N-acetylglucosamine 394:414 O-linked β-N-acetylglucosamine 385:414 O-linked β-N-acetylglucosamine (O-GlcNAc) 385:425 The post-translational addition and removal of O-linked β-N-acetylglucosamine (O-GlcNAc) also occurs on serine residues. 24381264 3 19 dep enzymes 506:512 arg1 β-N-acetylglucosamindase 545:568 β-N-acetylglucosamindase 545:568 β-N-acetylglucosamindase (O-GlcNAcase) 545:582 This, together with the high expression of the enzymes O-GlcNAc transferase (OGT) and β-N-acetylglucosamindase (O-GlcNAcase), suggests a potential role for O-GlcNAcylation in modifying synaptic efficacy and cognition. 24381264 3 19 dep enzymes 506:512 arg1 transferase 523:533 O-GlcNAc transferase 514:533 O-GlcNAc transferase (OGT) 514:539 This, together with the high expression of the enzymes O-GlcNAc transferase (OGT) and β-N-acetylglucosamindase (O-GlcNAcase), suggests a potential role for O-GlcNAcylation in modifying synaptic efficacy and cognition. 24381264 3 19 dep enzymes 506:512 arg1 enzymes 506:512 the enzymes 502:512 the enzymes O-GlcNAc transferase (OGT) and β-N-acetylglucosamindase (O-GlcNAcase) 502:582 This, together with the high expression of the enzymes O-GlcNAc transferase (OGT) and β-N-acetylglucosamindase (O-GlcNAcase), suggests a potential role for O-GlcNAcylation in modifying synaptic efficacy and cognition. 24381264 3 19 dep enzymes 506:512 arg1 O-GlcNAcase 571:581 O-GlcNAcase 571:581 O-GlcNAcase 571:581 This, together with the high expression of the enzymes O-GlcNAc transferase (OGT) and β-N-acetylglucosamindase (O-GlcNAcase), suggests a potential role for O-GlcNAcylation in modifying synaptic efficacy and cognition. 24381264 3 19 dep enzymes 506:512 arg1 OGT 536:538 OGT 536:538 OGT 536:538 This, together with the high expression of the enzymes O-GlcNAc transferase (OGT) and β-N-acetylglucosamindase (O-GlcNAcase), suggests a potential role for O-GlcNAcylation in modifying synaptic efficacy and cognition. 24381264 6 20 theme GluA2 1115:1119 arg1 subunits 1121:1128 AMPAR GluA2 subunits 1109:1128 AMPAR GluA2 subunits 1109:1128 This LTD requires AMPAR GluA2 subunits, which we demonstrate are O-GlcNAcylated. 24381264 5 21 theme hippocampal 1047:1057 arg1 synapses 1067:1074 hippocampal CA3-CA1 synapses 1047:1074 hippocampal CA3-CA1 synapses 1047:1074 We report that acutely increasing O-GlcNAcylation in Sprague Dawley rat hippocampal slices induces an NMDA receptor and protein kinase C-independent long-term depression (LTD) at hippocampal CA3-CA1 synapses (O-GcNAc LTD). 24381264 6 22 theme AMPAR 1109:1113 arg1 subunits 1121:1128 AMPAR GluA2 subunits 1109:1128 AMPAR GluA2 subunits 1109:1128 This LTD requires AMPAR GluA2 subunits, which we demonstrate are O-GlcNAcylated. 24381264 1 23 theme subunits 168:175 arg1 phosphorylation 127:141 Serine phosphorylation 120:141 Serine phosphorylation of AMPA receptor (AMPAR) subunits GluA1 and GluA2 120:191 Serine phosphorylation of AMPA receptor (AMPAR) subunits GluA1 and GluA2 modulates AMPAR trafficking during long-term changes in strength of hippocampal excitatory transmission required for normal learning and memory. 24381264 1 24 theme excitatory 273:282 arg1 transmission 284:295 hippocampal excitatory transmission 261:295 hippocampal excitatory transmission required for normal learning and memory 261:335 Serine phosphorylation of AMPA receptor (AMPAR) subunits GluA1 and GluA2 modulates AMPAR trafficking during long-term changes in strength of hippocampal excitatory transmission required for normal learning and memory. 24381264 5 25 theme increasing 891:900 arg1 O-GlcNAcylation 902:916 acutely increasing O-GlcNAcylation 883:916 acutely increasing O-GlcNAcylation in Sprague Dawley rat hippocampal slices 883:957 We report that acutely increasing O-GlcNAcylation in Sprague Dawley rat hippocampal slices induces an NMDA receptor and protein kinase C-independent long-term depression (LTD) at hippocampal CA3-CA1 synapses (O-GcNAc LTD). 24381264 2 26 theme β-N-acetylglucosamine 394:414 arg1 removal 374:380 removal 374:380 removal 374:380 The post-translational addition and removal of O-linked β-N-acetylglucosamine (O-GlcNAc) also occurs on serine residues. 24381264 2 26 theme β-N-acetylglucosamine 394:414 arg1 addition 361:368 post-translational addition 342:368 post-translational addition 342:368 The post-translational addition and removal of O-linked β-N-acetylglucosamine (O-GlcNAc) also occurs on serine residues. 24381264 0 27 theme receptor 24:31 arg1 GluA2 33:37 AMPA receptor GluA2 19:37 AMPA receptor GluA2 19:37 O-GlcNAcylation of AMPA receptor GluA2 is associated with a novel form of long-term depression at hippocampal synapses. 24381264 1 28 theme transmission 284:295 arg1 strength 249:256 strength 249:256 strength of hippocampal excitatory transmission required for normal learning and memory 249:335 Serine phosphorylation of AMPA receptor (AMPAR) subunits GluA1 and GluA2 modulates AMPAR trafficking during long-term changes in strength of hippocampal excitatory transmission required for normal learning and memory. 24381264 2 29 dep addition 361:368 arg1 The 338:340 The 338:340 The 338:340 The post-translational addition and removal of O-linked β-N-acetylglucosamine (O-GlcNAc) also occurs on serine residues. 24381264 2 30 theme serine 442:447 arg1 residues 449:456 serine residues 442:456 serine residues 442:456 The post-translational addition and removal of O-linked β-N-acetylglucosamine (O-GlcNAc) also occurs on serine residues. 24381264 0 31 theme AMPA 19:22 arg1 GluA2 33:37 AMPA receptor GluA2 19:37 AMPA receptor GluA2 19:37 O-GlcNAcylation of AMPA receptor GluA2 is associated with a novel form of long-term depression at hippocampal synapses. 24381264 8 32 theme cognitive 1560:1568 arg1 dysfunction 1570:1580 cognitive dysfunction 1560:1580 cognitive dysfunction in neurological diseases 1560:1605 Our findings provide evidence that O-GlcNAcylation dynamically modulates hippocampal synaptic function and learning and memory, and suggest that altered O-GlcNAc levels could underlie cognitive dysfunction in neurological diseases. 24381264 5 33 theme C-independent 1003:1015 arg1 depression 1027:1036 long-term depression 1017:1036 protein kinase C-independent long-term depression (LTD) at hippocampal CA3-CA1 synapses (O-GcNAc LTD) 988:1088 We report that acutely increasing O-GlcNAcylation in Sprague Dawley rat hippocampal slices induces an NMDA receptor and protein kinase C-independent long-term depression (LTD) at hippocampal CA3-CA1 synapses (O-GcNAc LTD). 24381264 5 33 theme C-independent 1003:1015 arg1 LTD 1039:1041 LTD 1039:1041 LTD 1039:1041 We report that acutely increasing O-GlcNAcylation in Sprague Dawley rat hippocampal slices induces an NMDA receptor and protein kinase C-independent long-term depression (LTD) at hippocampal CA3-CA1 synapses (O-GcNAc LTD). 24381264 5 33 theme C-independent 1003:1015 arg1 LTD 1085:1087 LTD 1085:1087 LTD 1085:1087 We report that acutely increasing O-GlcNAcylation in Sprague Dawley rat hippocampal slices induces an NMDA receptor and protein kinase C-independent long-term depression (LTD) at hippocampal CA3-CA1 synapses (O-GcNAc LTD). 24381264 5 34 from synapses 1067:1074 arg1 depression 1027:1036 long-term depression 1017:1036 protein kinase C-independent long-term depression (LTD) at hippocampal CA3-CA1 synapses (O-GcNAc LTD) 988:1088 We report that acutely increasing O-GlcNAcylation in Sprague Dawley rat hippocampal slices induces an NMDA receptor and protein kinase C-independent long-term depression (LTD) at hippocampal CA3-CA1 synapses (O-GcNAc LTD). 24381264 5 34 from synapses 1067:1074 arg1 LTD 1085:1087 LTD 1085:1087 LTD 1085:1087 We report that acutely increasing O-GlcNAcylation in Sprague Dawley rat hippocampal slices induces an NMDA receptor and protein kinase C-independent long-term depression (LTD) at hippocampal CA3-CA1 synapses (O-GcNAc LTD). 24381264 5 34 from synapses 1067:1074 arg1 LTD 1039:1041 LTD 1039:1041 LTD 1039:1041 We report that acutely increasing O-GlcNAcylation in Sprague Dawley rat hippocampal slices induces an NMDA receptor and protein kinase C-independent long-term depression (LTD) at hippocampal CA3-CA1 synapses (O-GcNAc LTD). 24381264 5 34 from synapses 1067:1074 arg1 receptor 975:982 an NMDA receptor 967:982 an NMDA receptor 967:982 We report that acutely increasing O-GlcNAcylation in Sprague Dawley rat hippocampal slices induces an NMDA receptor and protein kinase C-independent long-term depression (LTD) at hippocampal CA3-CA1 synapses (O-GcNAc LTD). 24381264 3 35 theme high 483:486 arg1 expression 488:497 the high expression 479:497 the high expression of the enzymes O-GlcNAc transferase (OGT) and β-N-acetylglucosamindase (O-GlcNAcase) 479:582 This, together with the high expression of the enzymes O-GlcNAc transferase (OGT) and β-N-acetylglucosamindase (O-GlcNAcase), suggests a potential role for O-GlcNAcylation in modifying synaptic efficacy and cognition. 24381264 3 36 theme enzymes 506:512 arg1 expression 488:497 the high expression 479:497 the high expression of the enzymes O-GlcNAc transferase (OGT) and β-N-acetylglucosamindase (O-GlcNAcase) 479:582 This, together with the high expression of the enzymes O-GlcNAc transferase (OGT) and β-N-acetylglucosamindase (O-GlcNAcase), suggests a potential role for O-GlcNAcylation in modifying synaptic efficacy and cognition. 24381264 0 37 from form 66:69 arg1 synapses 110:117 hippocampal synapses 98:117 hippocampal synapses 98:117 O-GlcNAcylation of AMPA receptor GluA2 is associated with a novel form of long-term depression at hippocampal synapses. 24381264 1 38 dep subunits 168:175 arg1 subunits 168:175 AMPA receptor (AMPAR) subunits GluA1 and GluA2 146:191 AMPA receptor (AMPAR) subunits GluA1 and GluA2 146:191 Serine phosphorylation of AMPA receptor (AMPAR) subunits GluA1 and GluA2 modulates AMPAR trafficking during long-term changes in strength of hippocampal excitatory transmission required for normal learning and memory. 24381264 1 38 dep subunits 168:175 arg1 GluA2 187:191 GluA2 187:191 GluA2 187:191 Serine phosphorylation of AMPA receptor (AMPAR) subunits GluA1 and GluA2 modulates AMPAR trafficking during long-term changes in strength of hippocampal excitatory transmission required for normal learning and memory. 24381264 1 38 dep subunits 168:175 arg1 GluA1 177:181 GluA1 177:181 GluA1 177:181 Serine phosphorylation of AMPA receptor (AMPAR) subunits GluA1 and GluA2 modulates AMPAR trafficking during long-term changes in strength of hippocampal excitatory transmission required for normal learning and memory. 24381264 0 39 theme GluA2 33:37 arg1 O-GlcNAcylation 0:14 O-GlcNAcylation 0:14 O-GlcNAcylation of AMPA receptor GluA2 0:37 O-GlcNAcylation of AMPA receptor GluA2 is associated with a novel form of long-term depression at hippocampal synapses. 24381264 1 40 theme normal 310:315 arg1 learning 317:324 learning 317:324 learning 317:324 Serine phosphorylation of AMPA receptor (AMPAR) subunits GluA1 and GluA2 modulates AMPAR trafficking during long-term changes in strength of hippocampal excitatory transmission required for normal learning and memory. 24381264 7 41 theme long-term 1215:1223 arg1 potentiation 1225:1236 long-term potentiation 1215:1236 long-term potentiation 1215:1236 Increasing O-GlcNAcylation interferes with long-term potentiation, and in hippocampal behavioral assays, it prevents novel object recognition and placement without affecting contextual fear conditioning. 24381264 7 42 theme behavioral 1258:1267 arg1 assays 1269:1274 hippocampal behavioral assays 1246:1274 hippocampal behavioral assays 1246:1274 Increasing O-GlcNAcylation interferes with long-term potentiation, and in hippocampal behavioral assays, it prevents novel object recognition and placement without affecting contextual fear conditioning. 24381264 1 43 theme AMPAR 203:207 arg1 trafficking 209:219 AMPAR trafficking 203:219 AMPAR trafficking 203:219 Serine phosphorylation of AMPA receptor (AMPAR) subunits GluA1 and GluA2 modulates AMPAR trafficking during long-term changes in strength of hippocampal excitatory transmission required for normal learning and memory. 24381264 5 44 theme Dawley 929:934 arg1 slices 952:957 Sprague Dawley rat hippocampal slices 921:957 Sprague Dawley rat hippocampal slices 921:957 We report that acutely increasing O-GlcNAcylation in Sprague Dawley rat hippocampal slices induces an NMDA receptor and protein kinase C-independent long-term depression (LTD) at hippocampal CA3-CA1 synapses (O-GcNAc LTD). 24381264 7 45 theme novel 1289:1293 arg1 recognition 1302:1312 novel object recognition 1289:1312 novel object recognition 1289:1312 Increasing O-GlcNAcylation interferes with long-term potentiation, and in hippocampal behavioral assays, it prevents novel object recognition and placement without affecting contextual fear conditioning. 24381264 8 46 from dysfunction 1570:1580 arg1 diseases 1598:1605 neurological diseases 1585:1605 neurological diseases 1585:1605 Our findings provide evidence that O-GlcNAcylation dynamically modulates hippocampal synaptic function and learning and memory, and suggest that altered O-GlcNAc levels could underlie cognitive dysfunction in neurological diseases. 24381264 6 47 dep demonstrate 1140:1150 arg1 O-GlcNAcylated 1156:1169 O-GlcNAcylated 1156:1169 O-GlcNAcylated 1156:1169 This LTD requires AMPAR GluA2 subunits, which we demonstrate are O-GlcNAcylated. 24381264 7 48 theme fear 1357:1360 arg1 conditioning 1362:1373 contextual fear conditioning 1346:1373 contextual fear conditioning 1346:1373 Increasing O-GlcNAcylation interferes with long-term potentiation, and in hippocampal behavioral assays, it prevents novel object recognition and placement without affecting contextual fear conditioning. 24381264 1 49 from changes 238:244 arg1 strength 249:256 strength 249:256 strength of hippocampal excitatory transmission required for normal learning and memory 249:335 Serine phosphorylation of AMPA receptor (AMPAR) subunits GluA1 and GluA2 modulates AMPAR trafficking during long-term changes in strength of hippocampal excitatory transmission required for normal learning and memory. 24381264 3 50 theme potential 596:604 arg1 role 606:609 a potential role 594:609 a potential role for O-GlcNAcylation in modifying synaptic efficacy and cognition 594:674 This, together with the high expression of the enzymes O-GlcNAc transferase (OGT) and β-N-acetylglucosamindase (O-GlcNAcase), suggests a potential role for O-GlcNAcylation in modifying synaptic efficacy and cognition. 24381264 2 51 theme post-translational 342:359 arg1 addition 361:368 post-translational addition 342:368 post-translational addition 342:368 The post-translational addition and removal of O-linked β-N-acetylglucosamine (O-GlcNAc) also occurs on serine residues. 24381264 8 52 theme neurological 1585:1596 arg1 diseases 1598:1605 neurological diseases 1585:1605 neurological diseases 1585:1605 Our findings provide evidence that O-GlcNAcylation dynamically modulates hippocampal synaptic function and learning and memory, and suggest that altered O-GlcNAc levels could underlie cognitive dysfunction in neurological diseases. 24381264 8 53 theme O-GlcNAc 1529:1536 arg1 levels 1538:1543 altered O-GlcNAc levels 1521:1543 altered O-GlcNAc levels 1521:1543 Our findings provide evidence that O-GlcNAcylation dynamically modulates hippocampal synaptic function and learning and memory, and suggest that altered O-GlcNAc levels could underlie cognitive dysfunction in neurological diseases. 24381264 1 54 theme Serine 120:125 arg1 phosphorylation 127:141 Serine phosphorylation 120:141 Serine phosphorylation of AMPA receptor (AMPAR) subunits GluA1 and GluA2 120:191 Serine phosphorylation of AMPA receptor (AMPAR) subunits GluA1 and GluA2 modulates AMPAR trafficking during long-term changes in strength of hippocampal excitatory transmission required for normal learning and memory. 24381264 8 55 theme synaptic 1461:1468 arg1 function 1470:1477 hippocampal synaptic function 1449:1477 hippocampal synaptic function 1449:1477 Our findings provide evidence that O-GlcNAcylation dynamically modulates hippocampal synaptic function and learning and memory, and suggest that altered O-GlcNAc levels could underlie cognitive dysfunction in neurological diseases. 24381264 3 56 theme synaptic 644:651 arg1 efficacy 653:660 synaptic efficacy 644:660 synaptic efficacy 644:660 This, together with the high expression of the enzymes O-GlcNAc transferase (OGT) and β-N-acetylglucosamindase (O-GlcNAcase), suggests a potential role for O-GlcNAcylation in modifying synaptic efficacy and cognition. 24381264 4 57 theme synaptic 702:709 arg1 proteins 711:718 key synaptic proteins 698:718 key synaptic proteins 698:718 Furthermore, because key synaptic proteins are O-GlcNAcylated, this modification may be as important to brain function as phosphorylation, yet its physiological significance remains unknown. 24381264 5 58 theme NMDA 970:973 arg1 receptor 975:982 an NMDA receptor 967:982 an NMDA receptor 967:982 We report that acutely increasing O-GlcNAcylation in Sprague Dawley rat hippocampal slices induces an NMDA receptor and protein kinase C-independent long-term depression (LTD) at hippocampal CA3-CA1 synapses (O-GcNAc LTD). 24381264 0 59 theme novel 60:64 arg1 form 66:69 a novel form 58:69 a novel form of long-term depression at hippocampal synapses 58:117 O-GlcNAcylation of AMPA receptor GluA2 is associated with a novel form of long-term depression at hippocampal synapses. 24381264 4 60 theme physiological 824:836 arg1 significance 838:849 its physiological significance 820:849 its physiological significance 820:849 Furthermore, because key synaptic proteins are O-GlcNAcylated, this modification may be as important to brain function as phosphorylation, yet its physiological significance remains unknown. 24381264 2 61 theme O-linked 385:392 arg1 O-GlcNAc 417:424 O-GlcNAc 417:424 O-GlcNAc 417:424 The post-translational addition and removal of O-linked β-N-acetylglucosamine (O-GlcNAc) also occurs on serine residues. 24381264 2 61 theme O-linked 385:392 arg1 β-N-acetylglucosamine 394:414 O-linked β-N-acetylglucosamine 385:414 O-linked β-N-acetylglucosamine (O-GlcNAc) 385:425 The post-translational addition and removal of O-linked β-N-acetylglucosamine (O-GlcNAc) also occurs on serine residues. 24381264 1 62 theme long-term 228:236 arg1 changes 238:244 long-term changes 228:244 long-term changes in strength of hippocampal excitatory transmission required for normal learning and memory 228:335 Serine phosphorylation of AMPA receptor (AMPAR) subunits GluA1 and GluA2 modulates AMPAR trafficking during long-term changes in strength of hippocampal excitatory transmission required for normal learning and memory. 24381264 7 63 theme object 1295:1300 arg1 recognition 1302:1312 novel object recognition 1289:1312 novel object recognition 1289:1312 Increasing O-GlcNAcylation interferes with long-term potentiation, and in hippocampal behavioral assays, it prevents novel object recognition and placement without affecting contextual fear conditioning. 24381264 7 64 theme hippocampal 1246:1256 arg1 assays 1269:1274 hippocampal behavioral assays 1246:1274 hippocampal behavioral assays 1246:1274 Increasing O-GlcNAcylation interferes with long-term potentiation, and in hippocampal behavioral assays, it prevents novel object recognition and placement without affecting contextual fear conditioning. 24381264 5 65 theme CA3-CA1 1059:1065 arg1 synapses 1067:1074 hippocampal CA3-CA1 synapses 1047:1074 hippocampal CA3-CA1 synapses 1047:1074 We report that acutely increasing O-GlcNAcylation in Sprague Dawley rat hippocampal slices induces an NMDA receptor and protein kinase C-independent long-term depression (LTD) at hippocampal CA3-CA1 synapses (O-GcNAc LTD). 24381264 1 66 theme AMPA 146:149 arg1 subunits 168:175 AMPA receptor (AMPAR) subunits GluA1 and GluA2 146:191 AMPA receptor (AMPAR) subunits GluA1 and GluA2 146:191 Serine phosphorylation of AMPA receptor (AMPAR) subunits GluA1 and GluA2 modulates AMPAR trafficking during long-term changes in strength of hippocampal excitatory transmission required for normal learning and memory. 24381264 1 66 theme AMPA 146:149 arg1 GluA2 187:191 GluA2 187:191 GluA2 187:191 Serine phosphorylation of AMPA receptor (AMPAR) subunits GluA1 and GluA2 modulates AMPAR trafficking during long-term changes in strength of hippocampal excitatory transmission required for normal learning and memory. 24381264 1 66 theme AMPA 146:149 arg1 GluA1 177:181 GluA1 177:181 GluA1 177:181 Serine phosphorylation of AMPA receptor (AMPAR) subunits GluA1 and GluA2 modulates AMPAR trafficking during long-term changes in strength of hippocampal excitatory transmission required for normal learning and memory. 24381264 0 67 from synapses 110:117 arg1 form 66:69 a novel form 58:69 a novel form of long-term depression at hippocampal synapses 58:117 O-GlcNAcylation of AMPA receptor GluA2 is associated with a novel form of long-term depression at hippocampal synapses. 24381264 0 67 from synapses 110:117 arg1 depression 84:93 long-term depression 74:93 long-term depression at hippocampal synapses 74:117 O-GlcNAcylation of AMPA receptor GluA2 is associated with a novel form of long-term depression at hippocampal synapses. 28687334 6 0 theme Cys 1000:1002 arg1 residues 1004:1011 conserved Cys residues 990:1011 conserved Cys residues 990:1011 The structure of AbCTSZ reveals amino acid sequences that are characteristic of the signal sequence, pro-peptide, peptidase-C1 papain family cysteine protease domain, mini-loop, HIP motif, N-linked glycosylation sites, active sites, and conserved Cys residues. 28687334 6 0 theme Cys 1000:1002 arg1 sequence 844:851 the signal sequence 833:851 the signal sequence 833:851 The structure of AbCTSZ reveals amino acid sequences that are characteristic of the signal sequence, pro-peptide, peptidase-C1 papain family cysteine protease domain, mini-loop, HIP motif, N-linked glycosylation sites, active sites, and conserved Cys residues. 28687334 11 1 theme disk 1803:1806 arg1 abalone 1808:1814 disk abalone 1803:1814 disk abalone 1803:1814 Higher levels of AbCTSZ transcripts were found in trochophore, gill, and hemocytes, highlighting its importance in the early development and immunity of disk abalone. 28687334 13 2 theme disk 2106:2109 arg1 abalone 2111:2117 disk abalone 2106:2117 disk abalone 2106:2117 Collectively, these lines of evidences suggest that AbCTSZ plays an indispensable role in the innate immunity of disk abalone. 28687334 10 3 theme Quantitative 1519:1530 arg1 qPCR 1547:1550 qPCR 1547:1550 qPCR 1547:1550 Quantitative real time PCR (qPCR) detected the transcripts of AbCTSZ in early developmental stages and in eight different tissues. 28687334 10 3 theme Quantitative 1519:1530 arg1 PCR 1542:1544 Quantitative real time PCR 1519:1544 Quantitative real time PCR (qPCR) 1519:1551 Quantitative real time PCR (qPCR) detected the transcripts of AbCTSZ in early developmental stages and in eight different tissues. 28687334 7 4 theme pairwise 1016:1023 arg1 comparison 1025:1034 A pairwise comparison 1014:1034 A pairwise comparison 1014:1034 A pairwise comparison revealed that AbCTSZ shared the highest amino acid homology with its molluscan counterpart from Crassostrea gigas. 28687334 2 5 theme host 261:264 arg1 defense 273:279 the host immune defense 257:279 the host immune defense 257:279 It participates in the host immune defense via phagocytosis, signal transduction, cell-cell communication, proliferation, and migration of immune cells such as monocytes, macrophages, and dendritic cells. 28687334 8 6 theme crucial 1223:1229 arg1 elements 1231:1238 functionally crucial elements 1210:1238 functionally crucial elements of AbCTSZ 1210:1248 A multiple alignment analysis revealed the conservation of functionally crucial elements of AbCTSZ, and a phylogenetic study further confirmed a proximal evolutionary relationship with its invertebrate counterparts. 28687334 8 7 theme multiple 1153:1160 arg1 analysis 1172:1179 A multiple alignment analysis 1151:1179 A multiple alignment analysis 1151:1179 A multiple alignment analysis revealed the conservation of functionally crucial elements of AbCTSZ, and a phylogenetic study further confirmed a proximal evolutionary relationship with its invertebrate counterparts. 28687334 6 8 theme acid 791:794 arg1 sequences 796:804 amino acid sequences 785:804 amino acid sequences that are characteristic of the signal sequence, pro-peptide, peptidase-C1 papain family cysteine protease domain, mini-loop, HIP motif, N-linked glycosylation sites, active sites, and conserved Cys residues 785:1011 The structure of AbCTSZ reveals amino acid sequences that are characteristic of the signal sequence, pro-peptide, peptidase-C1 papain family cysteine protease domain, mini-loop, HIP motif, N-linked glycosylation sites, active sites, and conserved Cys residues. 28687334 5 9 with mass 738:741 arg1 acids 716:720 318 amino acids 706:720 318 amino acids 706:720 AbCTSZ encodes a protein with 318 amino acids and a molecular mass of 36kDa. 28687334 9 10 theme genomic 1398:1404 arg1 structure 1406:1414 AbCTSZ genomic structure 1391:1414 AbCTSZ genomic structure 1391:1414 Further, an analysis of AbCTSZ genomic structure revealed seven exons separated by six introns, which differs from that of its vertebrate counterparts. 28687334 6 11 theme family 887:892 arg1 sequence 844:851 the signal sequence 833:851 the signal sequence 833:851 The structure of AbCTSZ reveals amino acid sequences that are characteristic of the signal sequence, pro-peptide, peptidase-C1 papain family cysteine protease domain, mini-loop, HIP motif, N-linked glycosylation sites, active sites, and conserved Cys residues. 28687334 6 11 theme family 887:892 arg1 domain 912:917 peptidase-C1 papain family cysteine protease domain 867:917 peptidase-C1 papain family cysteine protease domain 867:917 The structure of AbCTSZ reveals amino acid sequences that are characteristic of the signal sequence, pro-peptide, peptidase-C1 papain family cysteine protease domain, mini-loop, HIP motif, N-linked glycosylation sites, active sites, and conserved Cys residues. 28687334 4 12 theme disk 579:582 arg1 abalone 584:590 disk abalone 579:590 disk abalone 579:590 In this study, we sought to identify the CTSZ homolog from disk abalone (AbCTSZ) and characterize it at the molecular, genomic, and transcriptional levels. 28687334 10 13 theme time 1537:1540 arg1 qPCR 1547:1550 qPCR 1547:1550 qPCR 1547:1550 Quantitative real time PCR (qPCR) detected the transcripts of AbCTSZ in early developmental stages and in eight different tissues. 28687334 10 13 theme time 1537:1540 arg1 PCR 1542:1544 Quantitative real time PCR 1519:1544 Quantitative real time PCR (qPCR) 1519:1551 Quantitative real time PCR (qPCR) detected the transcripts of AbCTSZ in early developmental stages and in eight different tissues. 28687334 12 14 theme Vibrio 1861:1866 arg1 parahaemolyticus 1868:1883 Vibrio parahaemolyticus 1861:1883 Vibrio parahaemolyticus 1861:1883 In addition, we found that viable bacteria (Vibrio parahaemolyticus and Listeria monocytogenes) and bacterial lipopolysaccharides significantly modulated AbCTSZ transcription. 28687334 6 15 theme peptidase-C1 867:878 arg1 sequence 844:851 the signal sequence 833:851 the signal sequence 833:851 The structure of AbCTSZ reveals amino acid sequences that are characteristic of the signal sequence, pro-peptide, peptidase-C1 papain family cysteine protease domain, mini-loop, HIP motif, N-linked glycosylation sites, active sites, and conserved Cys residues. 28687334 6 15 theme peptidase-C1 867:878 arg1 domain 912:917 peptidase-C1 papain family cysteine protease domain 867:917 peptidase-C1 papain family cysteine protease domain 867:917 The structure of AbCTSZ reveals amino acid sequences that are characteristic of the signal sequence, pro-peptide, peptidase-C1 papain family cysteine protease domain, mini-loop, HIP motif, N-linked glycosylation sites, active sites, and conserved Cys residues. 28687334 0 16 theme transcriptional 106:120 arg1 profiling 122:130 transcriptional profiling 106:130 transcriptional profiling 106:130 A cysteine protease (cathepsin Z) from disk abalone, Haliotis discus discus: Genomic characterization and transcriptional profiling during bacterial infections. 28687334 13 17 theme innate 2087:2092 arg1 immunity 2094:2101 the innate immunity 2083:2101 the innate immunity of disk abalone 2083:2117 Collectively, these lines of evidences suggest that AbCTSZ plays an indispensable role in the innate immunity of disk abalone. 28687334 1 18 theme cysteine 193:200 arg1 protease 202:209 lysosomal cysteine protease 183:209 lysosomal cysteine protease of the papain superfamily 183:235 Cathepsin Z (CTSZ) is lysosomal cysteine protease of the papain superfamily. 28687334 4 19 theme genomic 639:645 arg1 levels 668:673 the molecular, genomic, and transcriptional levels 624:673 the molecular, genomic, and transcriptional levels 624:673 In this study, we sought to identify the CTSZ homolog from disk abalone (AbCTSZ) and characterize it at the molecular, genomic, and transcriptional levels. 28687334 6 20 theme sequence 844:851 arg1 characteristic 815:828 characteristic 815:828 characteristic 815:828 The structure of AbCTSZ reveals amino acid sequences that are characteristic of the signal sequence, pro-peptide, peptidase-C1 papain family cysteine protease domain, mini-loop, HIP motif, N-linked glycosylation sites, active sites, and conserved Cys residues. 28687334 5 21 with protein 693:699 arg1 acids 716:720 318 amino acids 706:720 318 amino acids 706:720 AbCTSZ encodes a protein with 318 amino acids and a molecular mass of 36kDa. 28687334 13 22 theme indispensable 2061:2073 arg1 role 2075:2078 an indispensable role 2058:2078 an indispensable role 2058:2078 Collectively, these lines of evidences suggest that AbCTSZ plays an indispensable role in the innate immunity of disk abalone. 28687334 3 23 theme host 505:508 arg1 immunity 510:517 host immunity 505:517 host immunity 505:517 Hence, CTSZ is also acknowledged as an acute-phase protein in host immunity. 28687334 11 24 theme transcripts 1674:1684 arg1 levels 1657:1662 Higher levels 1650:1662 Higher levels of AbCTSZ transcripts 1650:1684 Higher levels of AbCTSZ transcripts were found in trochophore, gill, and hemocytes, highlighting its importance in the early development and immunity of disk abalone. 28687334 0 25 theme disk 39:42 arg1 abalone 44:50 disk abalone 39:50 disk abalone 39:50 A cysteine protease (cathepsin Z) from disk abalone, Haliotis discus discus: Genomic characterization and transcriptional profiling during bacterial infections. 28687334 13 26 theme evidences 2022:2030 arg1 lines 2013:2017 these lines 2007:2017 these lines of evidences 2007:2030 Collectively, these lines of evidences suggest that AbCTSZ plays an indispensable role in the innate immunity of disk abalone. 28687334 4 27 theme molecular 628:636 arg1 levels 668:673 the molecular, genomic, and transcriptional levels 624:673 the molecular, genomic, and transcriptional levels 624:673 In this study, we sought to identify the CTSZ homolog from disk abalone (AbCTSZ) and characterize it at the molecular, genomic, and transcriptional levels. 28687334 8 28 with relationship 1318:1329 arg1 counterparts 1353:1364 its invertebrate counterparts 1336:1364 its invertebrate counterparts 1336:1364 A multiple alignment analysis revealed the conservation of functionally crucial elements of AbCTSZ, and a phylogenetic study further confirmed a proximal evolutionary relationship with its invertebrate counterparts. 28687334 7 29 theme Crassostrea 1132:1142 arg1 gigas 1144:1148 Crassostrea gigas 1132:1148 Crassostrea gigas 1132:1148 A pairwise comparison revealed that AbCTSZ shared the highest amino acid homology with its molluscan counterpart from Crassostrea gigas. 28687334 0 30 theme discus 62:67 arg1 protease 11:18 A cysteine protease 0:18 A cysteine protease (cathepsin Z) from disk abalone 0:50 A cysteine protease (cathepsin Z) from disk abalone, Haliotis discus discus: Genomic characterization and transcriptional profiling during bacterial infections. 28687334 0 30 theme discus 62:67 arg1 discus 69:74 Haliotis discus discus 53:74 Haliotis discus discus 53:74 A cysteine protease (cathepsin Z) from disk abalone, Haliotis discus discus: Genomic characterization and transcriptional profiling during bacterial infections. 28687334 12 31 theme viable 1844:1849 arg1 bacteria 1851:1858 viable bacteria 1844:1858 viable bacteria (Vibrio parahaemolyticus and Listeria monocytogenes) 1844:1911 In addition, we found that viable bacteria (Vibrio parahaemolyticus and Listeria monocytogenes) and bacterial lipopolysaccharides significantly modulated AbCTSZ transcription. 28687334 11 32 dep development 1775:1785 arg1 the 1765:1767 the 1765:1767 the 1765:1767 Higher levels of AbCTSZ transcripts were found in trochophore, gill, and hemocytes, highlighting its importance in the early development and immunity of disk abalone. 28687334 6 33 theme protease 903:910 arg1 sequence 844:851 the signal sequence 833:851 the signal sequence 833:851 The structure of AbCTSZ reveals amino acid sequences that are characteristic of the signal sequence, pro-peptide, peptidase-C1 papain family cysteine protease domain, mini-loop, HIP motif, N-linked glycosylation sites, active sites, and conserved Cys residues. 28687334 6 33 theme protease 903:910 arg1 domain 912:917 peptidase-C1 papain family cysteine protease domain 867:917 peptidase-C1 papain family cysteine protease domain 867:917 The structure of AbCTSZ reveals amino acid sequences that are characteristic of the signal sequence, pro-peptide, peptidase-C1 papain family cysteine protease domain, mini-loop, HIP motif, N-linked glycosylation sites, active sites, and conserved Cys residues. 28687334 10 34 theme early 1591:1595 arg1 stages 1611:1616 early developmental stages 1591:1616 early developmental stages 1591:1616 Quantitative real time PCR (qPCR) detected the transcripts of AbCTSZ in early developmental stages and in eight different tissues. 28687334 9 35 theme vertebrate 1494:1503 arg1 counterparts 1505:1516 its vertebrate counterparts 1490:1516 its vertebrate counterparts 1490:1516 Further, an analysis of AbCTSZ genomic structure revealed seven exons separated by six introns, which differs from that of its vertebrate counterparts. 28687334 3 36 theme acute-phase 482:492 arg1 protein 494:500 an acute-phase protein 479:500 an acute-phase protein in host immunity 479:517 Hence, CTSZ is also acknowledged as an acute-phase protein in host immunity. 28687334 3 36 theme acute-phase 482:492 arg1 CTSZ 450:453 CTSZ 450:453 CTSZ 450:453 Hence, CTSZ is also acknowledged as an acute-phase protein in host immunity. 28687334 8 37 theme proximal 1296:1303 arg1 relationship 1318:1329 a proximal evolutionary relationship 1294:1329 a proximal evolutionary relationship with its invertebrate counterparts 1294:1364 A multiple alignment analysis revealed the conservation of functionally crucial elements of AbCTSZ, and a phylogenetic study further confirmed a proximal evolutionary relationship with its invertebrate counterparts. 28687334 10 38 theme AbCTSZ 1581:1586 arg1 transcripts 1566:1576 the transcripts 1562:1576 the transcripts of AbCTSZ in early developmental stages and in eight different tissues 1562:1647 Quantitative real time PCR (qPCR) detected the transcripts of AbCTSZ in early developmental stages and in eight different tissues. 28687334 5 39 theme molecular 728:736 arg1 AbCTSZ 676:681 AbCTSZ 676:681 AbCTSZ 676:681 AbCTSZ encodes a protein with 318 amino acids and a molecular mass of 36kDa. 28687334 5 39 theme molecular 728:736 arg1 mass 738:741 a molecular mass 726:741 a molecular mass of 36kDa 726:750 AbCTSZ encodes a protein with 318 amino acids and a molecular mass of 36kDa. 28687334 6 40 theme active 972:977 arg1 sites 979:983 active sites 972:983 active sites 972:983 The structure of AbCTSZ reveals amino acid sequences that are characteristic of the signal sequence, pro-peptide, peptidase-C1 papain family cysteine protease domain, mini-loop, HIP motif, N-linked glycosylation sites, active sites, and conserved Cys residues. 28687334 6 40 theme active 972:977 arg1 sequence 844:851 the signal sequence 833:851 the signal sequence 833:851 The structure of AbCTSZ reveals amino acid sequences that are characteristic of the signal sequence, pro-peptide, peptidase-C1 papain family cysteine protease domain, mini-loop, HIP motif, N-linked glycosylation sites, active sites, and conserved Cys residues. 28687334 7 41 theme amino 1076:1080 arg1 homology 1087:1094 the highest amino acid homology 1064:1094 the highest amino acid homology 1064:1094 A pairwise comparison revealed that AbCTSZ shared the highest amino acid homology with its molluscan counterpart from Crassostrea gigas. 28687334 6 42 theme amino 785:789 arg1 sequences 796:804 amino acid sequences 785:804 amino acid sequences that are characteristic of the signal sequence, pro-peptide, peptidase-C1 papain family cysteine protease domain, mini-loop, HIP motif, N-linked glycosylation sites, active sites, and conserved Cys residues 785:1011 The structure of AbCTSZ reveals amino acid sequences that are characteristic of the signal sequence, pro-peptide, peptidase-C1 papain family cysteine protease domain, mini-loop, HIP motif, N-linked glycosylation sites, active sites, and conserved Cys residues. 28687334 0 43 theme cathepsin 21:29 arg1 protease 11:18 A cysteine protease 0:18 A cysteine protease (cathepsin Z) from disk abalone 0:50 A cysteine protease (cathepsin Z) from disk abalone, Haliotis discus discus: Genomic characterization and transcriptional profiling during bacterial infections. 28687334 0 43 theme cathepsin 21:29 arg1 Z 31:31 cathepsin Z 21:31 cathepsin Z 21:31 A cysteine protease (cathepsin Z) from disk abalone, Haliotis discus discus: Genomic characterization and transcriptional profiling during bacterial infections. 28687334 5 44 theme amino 710:714 arg1 acids 716:720 318 amino acids 706:720 318 amino acids 706:720 AbCTSZ encodes a protein with 318 amino acids and a molecular mass of 36kDa. 28687334 6 45 theme AbCTSZ 770:775 arg1 structure 757:765 The structure 753:765 The structure of AbCTSZ 753:775 The structure of AbCTSZ reveals amino acid sequences that are characteristic of the signal sequence, pro-peptide, peptidase-C1 papain family cysteine protease domain, mini-loop, HIP motif, N-linked glycosylation sites, active sites, and conserved Cys residues. 28687334 6 46 theme N-linked 942:949 arg1 sites 965:969 N-linked glycosylation sites 942:969 N-linked glycosylation sites 942:969 The structure of AbCTSZ reveals amino acid sequences that are characteristic of the signal sequence, pro-peptide, peptidase-C1 papain family cysteine protease domain, mini-loop, HIP motif, N-linked glycosylation sites, active sites, and conserved Cys residues. 28687334 6 46 theme N-linked 942:949 arg1 sequence 844:851 the signal sequence 833:851 the signal sequence 833:851 The structure of AbCTSZ reveals amino acid sequences that are characteristic of the signal sequence, pro-peptide, peptidase-C1 papain family cysteine protease domain, mini-loop, HIP motif, N-linked glycosylation sites, active sites, and conserved Cys residues. 28687334 2 47 theme cell-cell 320:328 arg1 communication 330:342 cell-cell communication 320:342 cell-cell communication 320:342 It participates in the host immune defense via phagocytosis, signal transduction, cell-cell communication, proliferation, and migration of immune cells such as monocytes, macrophages, and dendritic cells. 28687334 11 48 theme AbCTSZ 1667:1672 arg1 transcripts 1674:1684 AbCTSZ transcripts 1667:1684 AbCTSZ transcripts 1667:1684 Higher levels of AbCTSZ transcripts were found in trochophore, gill, and hemocytes, highlighting its importance in the early development and immunity of disk abalone. 28687334 10 49 theme different 1631:1639 arg1 tissues 1641:1647 eight different tissues 1625:1647 eight different tissues 1625:1647 Quantitative real time PCR (qPCR) detected the transcripts of AbCTSZ in early developmental stages and in eight different tissues. 28687334 0 50 dep protease 11:18 arg1 characterization 85:100 Genomic characterization 77:100 Genomic characterization 77:100 A cysteine protease (cathepsin Z) from disk abalone, Haliotis discus discus: Genomic characterization and transcriptional profiling during bacterial infections. 28687334 0 50 dep protease 11:18 arg1 profiling 122:130 transcriptional profiling 106:130 transcriptional profiling 106:130 A cysteine protease (cathepsin Z) from disk abalone, Haliotis discus discus: Genomic characterization and transcriptional profiling during bacterial infections. 28687334 2 51 theme cells 384:388 arg1 proliferation 345:357 proliferation 345:357 proliferation 345:357 It participates in the host immune defense via phagocytosis, signal transduction, cell-cell communication, proliferation, and migration of immune cells such as monocytes, macrophages, and dendritic cells. 28687334 2 51 theme cells 384:388 arg1 phagocytosis 285:296 phagocytosis 285:296 phagocytosis 285:296 It participates in the host immune defense via phagocytosis, signal transduction, cell-cell communication, proliferation, and migration of immune cells such as monocytes, macrophages, and dendritic cells. 28687334 2 51 theme cells 384:388 arg1 transduction 306:317 signal transduction 299:317 signal transduction 299:317 It participates in the host immune defense via phagocytosis, signal transduction, cell-cell communication, proliferation, and migration of immune cells such as monocytes, macrophages, and dendritic cells. 28687334 2 51 theme cells 384:388 arg1 communication 330:342 cell-cell communication 320:342 cell-cell communication 320:342 It participates in the host immune defense via phagocytosis, signal transduction, cell-cell communication, proliferation, and migration of immune cells such as monocytes, macrophages, and dendritic cells. 28687334 2 51 theme cells 384:388 arg1 migration 364:372 migration 364:372 migration 364:372 It participates in the host immune defense via phagocytosis, signal transduction, cell-cell communication, proliferation, and migration of immune cells such as monocytes, macrophages, and dendritic cells. 28687334 11 52 located found 1691:1695 arg2 levels 1657:1662 Higher levels 1650:1662 Higher levels of AbCTSZ transcripts 1650:1684 Higher levels of AbCTSZ transcripts were found in trochophore, gill, and hemocytes, highlighting its importance in the early development and immunity of disk abalone. 28687334 11 52 located found 1691:1695 arg1 gill 1713:1716 gill 1713:1716 gill 1713:1716 Higher levels of AbCTSZ transcripts were found in trochophore, gill, and hemocytes, highlighting its importance in the early development and immunity of disk abalone. 28687334 11 52 located found 1691:1695 arg1 hemocytes 1723:1731 hemocytes 1723:1731 hemocytes 1723:1731 Higher levels of AbCTSZ transcripts were found in trochophore, gill, and hemocytes, highlighting its importance in the early development and immunity of disk abalone. 28687334 11 52 located found 1691:1695 arg1 trochophore 1700:1710 trochophore 1700:1710 trochophore 1700:1710 Higher levels of AbCTSZ transcripts were found in trochophore, gill, and hemocytes, highlighting its importance in the early development and immunity of disk abalone. 28687334 11 53 theme abalone 1808:1814 arg1 immunity 1791:1798 immunity 1791:1798 immunity 1791:1798 Higher levels of AbCTSZ transcripts were found in trochophore, gill, and hemocytes, highlighting its importance in the early development and immunity of disk abalone. 28687334 11 53 theme abalone 1808:1814 arg1 development 1775:1785 early development 1769:1785 early development 1769:1785 Higher levels of AbCTSZ transcripts were found in trochophore, gill, and hemocytes, highlighting its importance in the early development and immunity of disk abalone. 28687334 12 54 theme AbCTSZ 1971:1976 arg1 transcription 1978:1990 AbCTSZ transcription 1971:1990 AbCTSZ transcription 1971:1990 In addition, we found that viable bacteria (Vibrio parahaemolyticus and Listeria monocytogenes) and bacterial lipopolysaccharides significantly modulated AbCTSZ transcription. 28687334 6 55 theme signal 837:842 arg1 mini-loop 920:928 mini-loop 920:928 mini-loop 920:928 The structure of AbCTSZ reveals amino acid sequences that are characteristic of the signal sequence, pro-peptide, peptidase-C1 papain family cysteine protease domain, mini-loop, HIP motif, N-linked glycosylation sites, active sites, and conserved Cys residues. 28687334 6 55 theme signal 837:842 arg1 sites 965:969 N-linked glycosylation sites 942:969 N-linked glycosylation sites 942:969 The structure of AbCTSZ reveals amino acid sequences that are characteristic of the signal sequence, pro-peptide, peptidase-C1 papain family cysteine protease domain, mini-loop, HIP motif, N-linked glycosylation sites, active sites, and conserved Cys residues. 28687334 6 55 theme signal 837:842 arg1 residues 1004:1011 conserved Cys residues 990:1011 conserved Cys residues 990:1011 The structure of AbCTSZ reveals amino acid sequences that are characteristic of the signal sequence, pro-peptide, peptidase-C1 papain family cysteine protease domain, mini-loop, HIP motif, N-linked glycosylation sites, active sites, and conserved Cys residues. 28687334 6 55 theme signal 837:842 arg1 sequence 844:851 the signal sequence 833:851 the signal sequence 833:851 The structure of AbCTSZ reveals amino acid sequences that are characteristic of the signal sequence, pro-peptide, peptidase-C1 papain family cysteine protease domain, mini-loop, HIP motif, N-linked glycosylation sites, active sites, and conserved Cys residues. 28687334 6 55 theme signal 837:842 arg1 motif 935:939 HIP motif 931:939 HIP motif 931:939 The structure of AbCTSZ reveals amino acid sequences that are characteristic of the signal sequence, pro-peptide, peptidase-C1 papain family cysteine protease domain, mini-loop, HIP motif, N-linked glycosylation sites, active sites, and conserved Cys residues. 28687334 6 55 theme signal 837:842 arg1 pro-peptide 854:864 pro-peptide 854:864 pro-peptide 854:864 The structure of AbCTSZ reveals amino acid sequences that are characteristic of the signal sequence, pro-peptide, peptidase-C1 papain family cysteine protease domain, mini-loop, HIP motif, N-linked glycosylation sites, active sites, and conserved Cys residues. 28687334 6 55 theme signal 837:842 arg1 sites 979:983 active sites 972:983 active sites 972:983 The structure of AbCTSZ reveals amino acid sequences that are characteristic of the signal sequence, pro-peptide, peptidase-C1 papain family cysteine protease domain, mini-loop, HIP motif, N-linked glycosylation sites, active sites, and conserved Cys residues. 28687334 6 55 theme signal 837:842 arg1 domain 912:917 peptidase-C1 papain family cysteine protease domain 867:917 peptidase-C1 papain family cysteine protease domain 867:917 The structure of AbCTSZ reveals amino acid sequences that are characteristic of the signal sequence, pro-peptide, peptidase-C1 papain family cysteine protease domain, mini-loop, HIP motif, N-linked glycosylation sites, active sites, and conserved Cys residues. 28687334 4 56 theme CTSZ 561:564 arg1 homolog 566:572 the CTSZ homolog 557:572 the CTSZ homolog from disk abalone 557:590 In this study, we sought to identify the CTSZ homolog from disk abalone (AbCTSZ) and characterize it at the molecular, genomic, and transcriptional levels. 28687334 1 57 theme superfamily 225:235 arg1 protease 202:209 lysosomal cysteine protease 183:209 lysosomal cysteine protease of the papain superfamily 183:235 Cathepsin Z (CTSZ) is lysosomal cysteine protease of the papain superfamily. 28687334 11 58 from importance 1751:1760 arg1 immunity 1791:1798 immunity 1791:1798 immunity 1791:1798 Higher levels of AbCTSZ transcripts were found in trochophore, gill, and hemocytes, highlighting its importance in the early development and immunity of disk abalone. 28687334 11 58 from importance 1751:1760 arg1 development 1775:1785 early development 1769:1785 early development 1769:1785 Higher levels of AbCTSZ transcripts were found in trochophore, gill, and hemocytes, highlighting its importance in the early development and immunity of disk abalone. 28687334 6 59 theme conserved 990:998 arg1 residues 1004:1011 conserved Cys residues 990:1011 conserved Cys residues 990:1011 The structure of AbCTSZ reveals amino acid sequences that are characteristic of the signal sequence, pro-peptide, peptidase-C1 papain family cysteine protease domain, mini-loop, HIP motif, N-linked glycosylation sites, active sites, and conserved Cys residues. 28687334 6 59 theme conserved 990:998 arg1 sequence 844:851 the signal sequence 833:851 the signal sequence 833:851 The structure of AbCTSZ reveals amino acid sequences that are characteristic of the signal sequence, pro-peptide, peptidase-C1 papain family cysteine protease domain, mini-loop, HIP motif, N-linked glycosylation sites, active sites, and conserved Cys residues. 28687334 10 60 theme real 1532:1535 arg1 qPCR 1547:1550 qPCR 1547:1550 qPCR 1547:1550 Quantitative real time PCR (qPCR) detected the transcripts of AbCTSZ in early developmental stages and in eight different tissues. 28687334 10 60 theme real 1532:1535 arg1 PCR 1542:1544 Quantitative real time PCR 1519:1544 Quantitative real time PCR (qPCR) 1519:1551 Quantitative real time PCR (qPCR) detected the transcripts of AbCTSZ in early developmental stages and in eight different tissues. 28687334 2 61 theme immune 266:271 arg1 defense 273:279 the host immune defense 257:279 the host immune defense 257:279 It participates in the host immune defense via phagocytosis, signal transduction, cell-cell communication, proliferation, and migration of immune cells such as monocytes, macrophages, and dendritic cells. 28687334 13 62 theme abalone 2111:2117 arg1 immunity 2094:2101 the innate immunity 2083:2101 the innate immunity of disk abalone 2083:2117 Collectively, these lines of evidences suggest that AbCTSZ plays an indispensable role in the innate immunity of disk abalone. 28687334 12 63 theme bacterial 1917:1925 arg1 lipopolysaccharides 1927:1945 bacterial lipopolysaccharides 1917:1945 bacterial lipopolysaccharides 1917:1945 In addition, we found that viable bacteria (Vibrio parahaemolyticus and Listeria monocytogenes) and bacterial lipopolysaccharides significantly modulated AbCTSZ transcription. 28687334 6 64 link N-linked 942:949 arg1 sites 965:969 N-linked glycosylation sites 942:969 N-linked glycosylation sites 942:969 The structure of AbCTSZ reveals amino acid sequences that are characteristic of the signal sequence, pro-peptide, peptidase-C1 papain family cysteine protease domain, mini-loop, HIP motif, N-linked glycosylation sites, active sites, and conserved Cys residues. 28687334 6 64 link N-linked 942:949 arg1 sequence 844:851 the signal sequence 833:851 the signal sequence 833:851 The structure of AbCTSZ reveals amino acid sequences that are characteristic of the signal sequence, pro-peptide, peptidase-C1 papain family cysteine protease domain, mini-loop, HIP motif, N-linked glycosylation sites, active sites, and conserved Cys residues. 28687334 1 65 theme Cathepsin 161:169 arg1 CTSZ 174:177 CTSZ 174:177 CTSZ 174:177 Cathepsin Z (CTSZ) is lysosomal cysteine protease of the papain superfamily. 28687334 1 65 theme Cathepsin 161:169 arg1 Z 171:171 Cathepsin Z 161:171 Cathepsin Z (CTSZ) 161:178 Cathepsin Z (CTSZ) is lysosomal cysteine protease of the papain superfamily. 28687334 10 66 from transcripts 1566:1576 arg1 tissues 1641:1647 eight different tissues 1625:1647 eight different tissues 1625:1647 Quantitative real time PCR (qPCR) detected the transcripts of AbCTSZ in early developmental stages and in eight different tissues. 28687334 10 66 from transcripts 1566:1576 arg1 stages 1611:1616 early developmental stages 1591:1616 early developmental stages 1591:1616 Quantitative real time PCR (qPCR) detected the transcripts of AbCTSZ in early developmental stages and in eight different tissues. 28687334 9 67 theme AbCTSZ 1391:1396 arg1 structure 1406:1414 AbCTSZ genomic structure 1391:1414 AbCTSZ genomic structure 1391:1414 Further, an analysis of AbCTSZ genomic structure revealed seven exons separated by six introns, which differs from that of its vertebrate counterparts. 28687334 12 68 theme Listeria 1889:1896 arg1 monocytogenes 1898:1910 Listeria monocytogenes 1889:1910 Listeria monocytogenes 1889:1910 In addition, we found that viable bacteria (Vibrio parahaemolyticus and Listeria monocytogenes) and bacterial lipopolysaccharides significantly modulated AbCTSZ transcription. 28687334 6 69 theme cysteine 894:901 arg1 sequence 844:851 the signal sequence 833:851 the signal sequence 833:851 The structure of AbCTSZ reveals amino acid sequences that are characteristic of the signal sequence, pro-peptide, peptidase-C1 papain family cysteine protease domain, mini-loop, HIP motif, N-linked glycosylation sites, active sites, and conserved Cys residues. 28687334 6 69 theme cysteine 894:901 arg1 domain 912:917 peptidase-C1 papain family cysteine protease domain 867:917 peptidase-C1 papain family cysteine protease domain 867:917 The structure of AbCTSZ reveals amino acid sequences that are characteristic of the signal sequence, pro-peptide, peptidase-C1 papain family cysteine protease domain, mini-loop, HIP motif, N-linked glycosylation sites, active sites, and conserved Cys residues. 28687334 8 70 theme alignment 1162:1170 arg1 analysis 1172:1179 A multiple alignment analysis 1151:1179 A multiple alignment analysis 1151:1179 A multiple alignment analysis revealed the conservation of functionally crucial elements of AbCTSZ, and a phylogenetic study further confirmed a proximal evolutionary relationship with its invertebrate counterparts. 28687334 4 71 from abalone 584:590 arg1 homolog 566:572 the CTSZ homolog 557:572 the CTSZ homolog from disk abalone 557:590 In this study, we sought to identify the CTSZ homolog from disk abalone (AbCTSZ) and characterize it at the molecular, genomic, and transcriptional levels. 28687334 9 72 theme structure 1406:1414 arg1 analysis 1379:1386 an analysis 1376:1386 an analysis of AbCTSZ genomic structure 1376:1414 Further, an analysis of AbCTSZ genomic structure revealed seven exons separated by six introns, which differs from that of its vertebrate counterparts. 28687334 6 73 theme papain 880:885 arg1 sequence 844:851 the signal sequence 833:851 the signal sequence 833:851 The structure of AbCTSZ reveals amino acid sequences that are characteristic of the signal sequence, pro-peptide, peptidase-C1 papain family cysteine protease domain, mini-loop, HIP motif, N-linked glycosylation sites, active sites, and conserved Cys residues. 28687334 6 73 theme papain 880:885 arg1 domain 912:917 peptidase-C1 papain family cysteine protease domain 867:917 peptidase-C1 papain family cysteine protease domain 867:917 The structure of AbCTSZ reveals amino acid sequences that are characteristic of the signal sequence, pro-peptide, peptidase-C1 papain family cysteine protease domain, mini-loop, HIP motif, N-linked glycosylation sites, active sites, and conserved Cys residues. 28687334 12 74 dep bacteria 1851:1858 arg1 parahaemolyticus 1868:1883 Vibrio parahaemolyticus 1861:1883 Vibrio parahaemolyticus 1861:1883 In addition, we found that viable bacteria (Vibrio parahaemolyticus and Listeria monocytogenes) and bacterial lipopolysaccharides significantly modulated AbCTSZ transcription. 28687334 12 74 dep bacteria 1851:1858 arg1 monocytogenes 1898:1910 Listeria monocytogenes 1889:1910 Listeria monocytogenes 1889:1910 In addition, we found that viable bacteria (Vibrio parahaemolyticus and Listeria monocytogenes) and bacterial lipopolysaccharides significantly modulated AbCTSZ transcription. 28687334 1 75 theme lysosomal 183:191 arg1 protease 202:209 lysosomal cysteine protease 183:209 lysosomal cysteine protease of the papain superfamily 183:235 Cathepsin Z (CTSZ) is lysosomal cysteine protease of the papain superfamily. 28687334 0 76 from abalone 44:50 arg1 protease 11:18 A cysteine protease 0:18 A cysteine protease (cathepsin Z) from disk abalone 0:50 A cysteine protease (cathepsin Z) from disk abalone, Haliotis discus discus: Genomic characterization and transcriptional profiling during bacterial infections. 28687334 0 76 from abalone 44:50 arg1 Z 31:31 cathepsin Z 21:31 cathepsin Z 21:31 A cysteine protease (cathepsin Z) from disk abalone, Haliotis discus discus: Genomic characterization and transcriptional profiling during bacterial infections. 28687334 0 76 from abalone 44:50 arg1 discus 69:74 Haliotis discus discus 53:74 Haliotis discus discus 53:74 A cysteine protease (cathepsin Z) from disk abalone, Haliotis discus discus: Genomic characterization and transcriptional profiling during bacterial infections. 28687334 0 77 theme bacterial 139:147 arg1 infections 149:158 bacterial infections 139:158 bacterial infections 139:158 A cysteine protease (cathepsin Z) from disk abalone, Haliotis discus discus: Genomic characterization and transcriptional profiling during bacterial infections. 28687334 7 78 from gigas 1144:1148 arg1 counterpart 1115:1125 its molluscan counterpart 1101:1125 its molluscan counterpart from Crassostrea gigas 1101:1148 A pairwise comparison revealed that AbCTSZ shared the highest amino acid homology with its molluscan counterpart from Crassostrea gigas. 28687334 8 79 theme elements 1231:1238 arg1 conservation 1194:1205 the conservation 1190:1205 the conservation of functionally crucial elements of AbCTSZ 1190:1248 A multiple alignment analysis revealed the conservation of functionally crucial elements of AbCTSZ, and a phylogenetic study further confirmed a proximal evolutionary relationship with its invertebrate counterparts. 28687334 11 80 theme early 1769:1773 arg1 development 1775:1785 early development 1769:1785 early development 1769:1785 Higher levels of AbCTSZ transcripts were found in trochophore, gill, and hemocytes, highlighting its importance in the early development and immunity of disk abalone. 28687334 4 81 dep identify 548:555 arg1 AbCTSZ 593:598 AbCTSZ 593:598 AbCTSZ 593:598 In this study, we sought to identify the CTSZ homolog from disk abalone (AbCTSZ) and characterize it at the molecular, genomic, and transcriptional levels. 28687334 5 82 theme 36kDa 746:750 arg1 mass 738:741 a molecular mass 726:741 a molecular mass of 36kDa 726:750 AbCTSZ encodes a protein with 318 amino acids and a molecular mass of 36kDa. 28687334 5 82 theme 36kDa 746:750 arg1 AbCTSZ 676:681 AbCTSZ 676:681 AbCTSZ 676:681 AbCTSZ encodes a protein with 318 amino acids and a molecular mass of 36kDa. 28687334 5 82 theme 36kDa 746:750 arg1 protein 693:699 a protein 691:699 a protein with 318 amino acids 691:720 AbCTSZ encodes a protein with 318 amino acids and a molecular mass of 36kDa. 28687334 6 83 theme HIP 931:933 arg1 sequence 844:851 the signal sequence 833:851 the signal sequence 833:851 The structure of AbCTSZ reveals amino acid sequences that are characteristic of the signal sequence, pro-peptide, peptidase-C1 papain family cysteine protease domain, mini-loop, HIP motif, N-linked glycosylation sites, active sites, and conserved Cys residues. 28687334 6 83 theme HIP 931:933 arg1 motif 935:939 HIP motif 931:939 HIP motif 931:939 The structure of AbCTSZ reveals amino acid sequences that are characteristic of the signal sequence, pro-peptide, peptidase-C1 papain family cysteine protease domain, mini-loop, HIP motif, N-linked glycosylation sites, active sites, and conserved Cys residues. 28687334 8 84 theme AbCTSZ 1243:1248 arg1 elements 1231:1238 functionally crucial elements 1210:1238 functionally crucial elements of AbCTSZ 1210:1248 A multiple alignment analysis revealed the conservation of functionally crucial elements of AbCTSZ, and a phylogenetic study further confirmed a proximal evolutionary relationship with its invertebrate counterparts. 28687334 3 85 from protein 494:500 arg1 immunity 510:517 host immunity 505:517 host immunity 505:517 Hence, CTSZ is also acknowledged as an acute-phase protein in host immunity. 28687334 0 86 theme Haliotis 53:60 arg1 protease 11:18 A cysteine protease 0:18 A cysteine protease (cathepsin Z) from disk abalone 0:50 A cysteine protease (cathepsin Z) from disk abalone, Haliotis discus discus: Genomic characterization and transcriptional profiling during bacterial infections. 28687334 0 86 theme Haliotis 53:60 arg1 discus 69:74 Haliotis discus discus 53:74 Haliotis discus discus 53:74 A cysteine protease (cathepsin Z) from disk abalone, Haliotis discus discus: Genomic characterization and transcriptional profiling during bacterial infections. 28687334 7 87 theme molluscan 1105:1113 arg1 counterpart 1115:1125 its molluscan counterpart 1101:1125 its molluscan counterpart from Crassostrea gigas 1101:1148 A pairwise comparison revealed that AbCTSZ shared the highest amino acid homology with its molluscan counterpart from Crassostrea gigas. 28687334 8 88 theme phylogenetic 1257:1268 arg1 study 1270:1274 a phylogenetic study 1255:1274 a phylogenetic study 1255:1274 A multiple alignment analysis revealed the conservation of functionally crucial elements of AbCTSZ, and a phylogenetic study further confirmed a proximal evolutionary relationship with its invertebrate counterparts. 28687334 0 89 theme Genomic 77:83 arg1 characterization 85:100 Genomic characterization 77:100 Genomic characterization 77:100 A cysteine protease (cathepsin Z) from disk abalone, Haliotis discus discus: Genomic characterization and transcriptional profiling during bacterial infections. 28687334 0 90 theme cysteine 2:9 arg1 protease 11:18 A cysteine protease 0:18 A cysteine protease (cathepsin Z) from disk abalone 0:50 A cysteine protease (cathepsin Z) from disk abalone, Haliotis discus discus: Genomic characterization and transcriptional profiling during bacterial infections. 28687334 0 90 theme cysteine 2:9 arg1 Z 31:31 cathepsin Z 21:31 cathepsin Z 21:31 A cysteine protease (cathepsin Z) from disk abalone, Haliotis discus discus: Genomic characterization and transcriptional profiling during bacterial infections. 28687334 0 90 theme cysteine 2:9 arg1 discus 69:74 Haliotis discus discus 53:74 Haliotis discus discus 53:74 A cysteine protease (cathepsin Z) from disk abalone, Haliotis discus discus: Genomic characterization and transcriptional profiling during bacterial infections. 28687334 4 91 theme transcriptional 652:666 arg1 levels 668:673 the molecular, genomic, and transcriptional levels 624:673 the molecular, genomic, and transcriptional levels 624:673 In this study, we sought to identify the CTSZ homolog from disk abalone (AbCTSZ) and characterize it at the molecular, genomic, and transcriptional levels. 28687334 7 92 theme highest 1068:1074 arg1 homology 1087:1094 the highest amino acid homology 1064:1094 the highest amino acid homology 1064:1094 A pairwise comparison revealed that AbCTSZ shared the highest amino acid homology with its molluscan counterpart from Crassostrea gigas. 28687334 8 93 theme evolutionary 1305:1316 arg1 relationship 1318:1329 a proximal evolutionary relationship 1294:1329 a proximal evolutionary relationship with its invertebrate counterparts 1294:1364 A multiple alignment analysis revealed the conservation of functionally crucial elements of AbCTSZ, and a phylogenetic study further confirmed a proximal evolutionary relationship with its invertebrate counterparts. 28687334 6 94 theme glycosylation 951:963 arg1 sites 965:969 N-linked glycosylation sites 942:969 N-linked glycosylation sites 942:969 The structure of AbCTSZ reveals amino acid sequences that are characteristic of the signal sequence, pro-peptide, peptidase-C1 papain family cysteine protease domain, mini-loop, HIP motif, N-linked glycosylation sites, active sites, and conserved Cys residues. 28687334 6 94 theme glycosylation 951:963 arg1 sequence 844:851 the signal sequence 833:851 the signal sequence 833:851 The structure of AbCTSZ reveals amino acid sequences that are characteristic of the signal sequence, pro-peptide, peptidase-C1 papain family cysteine protease domain, mini-loop, HIP motif, N-linked glycosylation sites, active sites, and conserved Cys residues. 28687334 2 95 theme immune 377:382 arg1 cells 436:440 dendritic cells 426:440 dendritic cells 426:440 It participates in the host immune defense via phagocytosis, signal transduction, cell-cell communication, proliferation, and migration of immune cells such as monocytes, macrophages, and dendritic cells. 28687334 2 95 theme immune 377:382 arg1 macrophages 409:419 macrophages 409:419 macrophages 409:419 It participates in the host immune defense via phagocytosis, signal transduction, cell-cell communication, proliferation, and migration of immune cells such as monocytes, macrophages, and dendritic cells. 28687334 2 95 theme immune 377:382 arg1 cells 384:388 immune cells 377:388 immune cells such as monocytes, macrophages, and dendritic cells 377:440 It participates in the host immune defense via phagocytosis, signal transduction, cell-cell communication, proliferation, and migration of immune cells such as monocytes, macrophages, and dendritic cells. 28687334 2 95 theme immune 377:382 arg1 monocytes 398:406 monocytes 398:406 monocytes 398:406 It participates in the host immune defense via phagocytosis, signal transduction, cell-cell communication, proliferation, and migration of immune cells such as monocytes, macrophages, and dendritic cells. 28687334 6 96 gly glycosylation 951:963 arg2 sequence 844:851 the signal sequence 833:851 the signal sequence 833:851 The structure of AbCTSZ reveals amino acid sequences that are characteristic of the signal sequence, pro-peptide, peptidase-C1 papain family cysteine protease domain, mini-loop, HIP motif, N-linked glycosylation sites, active sites, and conserved Cys residues. 28687334 6 96 gly glycosylation 951:963 arg2 sites 965:969 N-linked glycosylation sites 942:969 N-linked glycosylation sites 942:969 The structure of AbCTSZ reveals amino acid sequences that are characteristic of the signal sequence, pro-peptide, peptidase-C1 papain family cysteine protease domain, mini-loop, HIP motif, N-linked glycosylation sites, active sites, and conserved Cys residues. 28687334 10 97 theme developmental 1597:1609 arg1 stages 1611:1616 early developmental stages 1591:1616 early developmental stages 1591:1616 Quantitative real time PCR (qPCR) detected the transcripts of AbCTSZ in early developmental stages and in eight different tissues. 28687334 2 98 theme dendritic 426:434 arg1 cells 436:440 dendritic cells 426:440 dendritic cells 426:440 It participates in the host immune defense via phagocytosis, signal transduction, cell-cell communication, proliferation, and migration of immune cells such as monocytes, macrophages, and dendritic cells. 28687334 8 99 theme invertebrate 1340:1351 arg1 counterparts 1353:1364 its invertebrate counterparts 1336:1364 its invertebrate counterparts 1336:1364 A multiple alignment analysis revealed the conservation of functionally crucial elements of AbCTSZ, and a phylogenetic study further confirmed a proximal evolutionary relationship with its invertebrate counterparts. 28687334 11 100 theme Higher 1650:1655 arg1 levels 1657:1662 Higher levels 1650:1662 Higher levels of AbCTSZ transcripts 1650:1684 Higher levels of AbCTSZ transcripts were found in trochophore, gill, and hemocytes, highlighting its importance in the early development and immunity of disk abalone. 28687334 2 101 theme signal 299:304 arg1 transduction 306:317 signal transduction 299:317 signal transduction 299:317 It participates in the host immune defense via phagocytosis, signal transduction, cell-cell communication, proliferation, and migration of immune cells such as monocytes, macrophages, and dendritic cells. 28687334 7 102 theme acid 1082:1085 arg1 homology 1087:1094 the highest amino acid homology 1064:1094 the highest amino acid homology 1064:1094 A pairwise comparison revealed that AbCTSZ shared the highest amino acid homology with its molluscan counterpart from Crassostrea gigas. 28687334 1 103 theme papain 218:223 arg1 superfamily 225:235 the papain superfamily 214:235 the papain superfamily 214:235 Cathepsin Z (CTSZ) is lysosomal cysteine protease of the papain superfamily. 28635997 10 0 theme cancer 1837:1842 arg1 patients 1844:1851 stage III-IV breast cancer patients 1817:1851 stage III-IV breast cancer patients (n = 20) 1817:1860 When applied to blood plasma samples from stage III-IV breast cancer patients (n = 20) and age-matched controls (n = 20), the SCF procedure facilitated identification of three glycan nodes with significantly different distributions between the cases and controls (ROC c-statistics > 0.75; p < 0.01). 28635997 10 0 theme cancer 1837:1842 arg1 n 1854:1854 n = 20 1854:1859 n = 20 1854:1859 When applied to blood plasma samples from stage III-IV breast cancer patients (n = 20) and age-matched controls (n = 20), the SCF procedure facilitated identification of three glycan nodes with significantly different distributions between the cases and controls (ROC c-statistics > 0.75; p < 0.01). 28635997 9 1 theme glycan 1587:1592 arg1 analysis 1602:1609 glycan linkage analysis 1587:1609 glycan linkage analysis of pooled glycans from unfractionated blood plasma 1587:1660 When the SCF procedure was employed upstream to hydrolysis, reduction and acetylation for glycan linkage analysis of pooled glycans from unfractionated blood plasma, analytical reproducibility was on par with that from previous spin column-based "glycan node" analysis results. 28635997 10 2 theme different 1983:1991 arg1 distributions 1993:2005 significantly different distributions 1969:2005 significantly different distributions between the cases and controls (ROC c-statistics > 0.75; p < 0.01) 1969:2072 When applied to blood plasma samples from stage III-IV breast cancer patients (n = 20) and age-matched controls (n = 20), the SCF procedure facilitated identification of three glycan nodes with significantly different distributions between the cases and controls (ROC c-statistics > 0.75; p < 0.01). 28635997 10 3 theme = 1856:1856 arg1 patients 1844:1851 stage III-IV breast cancer patients 1817:1851 stage III-IV breast cancer patients (n = 20) 1817:1860 When applied to blood plasma samples from stage III-IV breast cancer patients (n = 20) and age-matched controls (n = 20), the SCF procedure facilitated identification of three glycan nodes with significantly different distributions between the cases and controls (ROC c-statistics > 0.75; p < 0.01). 28635997 10 3 theme = 1856:1856 arg1 n 1854:1854 n = 20 1854:1859 n = 20 1854:1859 When applied to blood plasma samples from stage III-IV breast cancer patients (n = 20) and age-matched controls (n = 20), the SCF procedure facilitated identification of three glycan nodes with significantly different distributions between the cases and controls (ROC c-statistics > 0.75; p < 0.01). 28635997 5 4 theme degradation 861:871 arg1 risk 836:839 the risk 832:839 the risk of glycan oxidative degradation 832:871 The SCF procedure involves neutralization of NaOH beads by acidified phosphate buffer, which eliminates the risk of glycan oxidative degradation and avoids the use of spin columns. 28635997 9 5 theme pooled 1614:1619 arg1 glycans 1621:1627 pooled glycans 1614:1627 pooled glycans from unfractionated blood plasma 1614:1660 When the SCF procedure was employed upstream to hydrolysis, reduction and acetylation for glycan linkage analysis of pooled glycans from unfractionated blood plasma, analytical reproducibility was on par with that from previous spin column-based "glycan node" analysis results. 28635997 6 6 theme spin 1123:1126 arg1 procedures 1141:1150 some widely-used spin column-based procedures 1106:1150 some widely-used spin column-based procedures 1106:1150 Optimization of the new permethylation procedure provided high permethylation efficiency for both hexose (>98%) and HexNAc (>99%) residues-yields which were comparable to (or better than) those of some widely-used spin column-based procedures. 28635997 11 7 theme intact 2150:2155 arg1 analysis 2164:2171 intact glycan analysis 2150:2171 intact glycan analysis 2150:2171 In summary, the SCF permethylation procedure expedites and economizes both intact glycan analysis and linkage analysis of glycans from whole biospecimens. 28635997 6 8 theme permethylation 972:985 arg1 efficiency 987:996 high permethylation efficiency 967:996 high permethylation efficiency for both hexose (>98%) and HexNAc (>99%) residues-yields which were comparable to (or better than) those of some widely-used spin column-based procedures 967:1150 Optimization of the new permethylation procedure provided high permethylation efficiency for both hexose (>98%) and HexNAc (>99%) residues-yields which were comparable to (or better than) those of some widely-used spin column-based procedures. 28635997 10 9 theme age-matched 1866:1876 arg1 controls 1878:1885 age-matched controls 1866:1885 age-matched controls (n = 20) 1866:1894 When applied to blood plasma samples from stage III-IV breast cancer patients (n = 20) and age-matched controls (n = 20), the SCF procedure facilitated identification of three glycan nodes with significantly different distributions between the cases and controls (ROC c-statistics > 0.75; p < 0.01). 28635997 10 9 theme age-matched 1866:1876 arg1 n 1888:1888 n = 20 1888:1893 n = 20 1888:1893 When applied to blood plasma samples from stage III-IV breast cancer patients (n = 20) and age-matched controls (n = 20), the SCF procedure facilitated identification of three glycan nodes with significantly different distributions between the cases and controls (ROC c-statistics > 0.75; p < 0.01). 28635997 11 10 from biospecimens 2216:2227 arg1 glycans 2197:2203 glycans 2197:2203 glycans from whole biospecimens 2197:2227 In summary, the SCF permethylation procedure expedites and economizes both intact glycan analysis and linkage analysis of glycans from whole biospecimens. 28635997 11 10 from biospecimens 2216:2227 arg1 analysis 2164:2171 intact glycan analysis 2150:2171 intact glycan analysis 2150:2171 In summary, the SCF permethylation procedure expedites and economizes both intact glycan analysis and linkage analysis of glycans from whole biospecimens. 28635997 11 10 from biospecimens 2216:2227 arg1 analysis 2185:2192 linkage analysis 2177:2192 linkage analysis 2177:2192 In summary, the SCF permethylation procedure expedites and economizes both intact glycan analysis and linkage analysis of glycans from whole biospecimens. 28635997 11 10 from biospecimens 2216:2227 arg1 economizes 2134:2143 economizes 2134:2143 economizes 2134:2143 In summary, the SCF permethylation procedure expedites and economizes both intact glycan analysis and linkage analysis of glycans from whole biospecimens. 28635997 9 11 theme blood 1649:1653 arg1 plasma 1655:1660 unfractionated blood plasma 1634:1660 unfractionated blood plasma 1634:1660 When the SCF procedure was employed upstream to hydrolysis, reduction and acetylation for glycan linkage analysis of pooled glycans from unfractionated blood plasma, analytical reproducibility was on par with that from previous spin column-based "glycan node" analysis results. 28635997 10 12 theme ROC 2039:2041 arg1 > 2056:2056 ROC c-statistics > 0.75 2039:2061 ROC c-statistics > 0.75; p < 0.01 2039:2071 When applied to blood plasma samples from stage III-IV breast cancer patients (n = 20) and age-matched controls (n = 20), the SCF procedure facilitated identification of three glycan nodes with significantly different distributions between the cases and controls (ROC c-statistics > 0.75; p < 0.01). 28635997 4 13 theme glycan 654:659 arg1 analysis 661:668 intact glycan analysis 647:668 intact glycan analysis 647:668 Here we describe a spin column-free (SCF) glycan permethylation procedure that is applicable to both O- and N-linked glycans and can be employed upstream to intact glycan analysis by MALDI-MS, ESI-MS, or glycan linkage analysis by GC-MS. 28635997 9 14 theme node 1751:1754 arg1 " 1755:1755 column-based "glycan node" 1730:1755 previous spin column-based "glycan node" analysis results 1716:1772 When the SCF procedure was employed upstream to hydrolysis, reduction and acetylation for glycan linkage analysis of pooled glycans from unfractionated blood plasma, analytical reproducibility was on par with that from previous spin column-based "glycan node" analysis results. 28635997 5 15 theme glycan 844:849 arg1 degradation 861:871 glycan oxidative degradation 844:871 glycan oxidative degradation 844:871 The SCF procedure involves neutralization of NaOH beads by acidified phosphate buffer, which eliminates the risk of glycan oxidative degradation and avoids the use of spin columns. 28635997 6 16 theme permethylation 933:946 arg1 procedure 948:956 the new permethylation procedure 925:956 the new permethylation procedure 925:956 Optimization of the new permethylation procedure provided high permethylation efficiency for both hexose (>98%) and HexNAc (>99%) residues-yields which were comparable to (or better than) those of some widely-used spin column-based procedures. 28635997 10 17 theme < 2066:2066 arg1 p 2064:2064 p < 0.01 2064:2071 ROC c-statistics > 0.75; p < 0.01 2039:2071 When applied to blood plasma samples from stage III-IV breast cancer patients (n = 20) and age-matched controls (n = 20), the SCF procedure facilitated identification of three glycan nodes with significantly different distributions between the cases and controls (ROC c-statistics > 0.75; p < 0.01). 28635997 10 18 theme = 1890:1890 arg1 controls 1878:1885 age-matched controls 1866:1885 age-matched controls (n = 20) 1866:1894 When applied to blood plasma samples from stage III-IV breast cancer patients (n = 20) and age-matched controls (n = 20), the SCF procedure facilitated identification of three glycan nodes with significantly different distributions between the cases and controls (ROC c-statistics > 0.75; p < 0.01). 28635997 10 18 theme = 1890:1890 arg1 n 1888:1888 n = 20 1888:1893 n = 20 1888:1893 When applied to blood plasma samples from stage III-IV breast cancer patients (n = 20) and age-matched controls (n = 20), the SCF procedure facilitated identification of three glycan nodes with significantly different distributions between the cases and controls (ROC c-statistics > 0.75; p < 0.01). 28635997 8 19 theme O-glycans 1408:1416 arg1 yield 1399:1403 overall yield 1391:1403 overall yield of O-glycans 1391:1416 Recovery of intact N-glycans was significantly better with the SCF procedure (p < 0.05), but overall yield of O-glycans was similar or slightly diminished (p < 0.05 for tetrasaccharides or smaller). 28635997 2 20 theme permethylation 253:266 arg1 efficiency 268:277 permethylation efficiency 253:277 permethylation efficiency 253:277 Since that time, permethylation procedures have been continually modified to improve permethylation efficiency and qualitative applicability. 28635997 3 21 theme preparation 347:357 arg1 steps 359:363 laborious preparation steps 337:363 laborious preparation steps 337:363 Typically, however, either laborious preparation steps or cumbersome and uneconomical spin columns have been needed to obtain decent permethylation yields on small glycan samples. 28635997 9 22 with par 1697:1699 arg1 that 1706:1709 that 1706:1709 that 1706:1709 When the SCF procedure was employed upstream to hydrolysis, reduction and acetylation for glycan linkage analysis of pooled glycans from unfractionated blood plasma, analytical reproducibility was on par with that from previous spin column-based "glycan node" analysis results. 28635997 4 23 theme glycan 694:699 arg1 analysis 709:716 glycan linkage analysis 694:716 glycan linkage analysis 694:716 Here we describe a spin column-free (SCF) glycan permethylation procedure that is applicable to both O- and N-linked glycans and can be employed upstream to intact glycan analysis by MALDI-MS, ESI-MS, or glycan linkage analysis by GC-MS. 28635997 5 24 theme NaOH 773:776 arg1 beads 778:782 NaOH beads 773:782 NaOH beads 773:782 The SCF procedure involves neutralization of NaOH beads by acidified phosphate buffer, which eliminates the risk of glycan oxidative degradation and avoids the use of spin columns. 28635997 5 25 theme spin 895:898 arg1 columns 900:906 spin columns 895:906 spin columns 895:906 The SCF procedure involves neutralization of NaOH beads by acidified phosphate buffer, which eliminates the risk of glycan oxidative degradation and avoids the use of spin columns. 28635997 9 26 from plasma 1655:1660 arg1 analysis 1602:1609 glycan linkage analysis 1587:1609 glycan linkage analysis of pooled glycans from unfractionated blood plasma 1587:1660 When the SCF procedure was employed upstream to hydrolysis, reduction and acetylation for glycan linkage analysis of pooled glycans from unfractionated blood plasma, analytical reproducibility was on par with that from previous spin column-based "glycan node" analysis results. 28635997 9 26 from plasma 1655:1660 arg1 glycans 1621:1627 pooled glycans 1614:1627 pooled glycans from unfractionated blood plasma 1614:1660 When the SCF procedure was employed upstream to hydrolysis, reduction and acetylation for glycan linkage analysis of pooled glycans from unfractionated blood plasma, analytical reproducibility was on par with that from previous spin column-based "glycan node" analysis results. 28635997 8 27 theme intact 1310:1315 arg1 N-glycans 1317:1325 intact N-glycans 1310:1325 intact N-glycans 1310:1325 Recovery of intact N-glycans was significantly better with the SCF procedure (p < 0.05), but overall yield of O-glycans was similar or slightly diminished (p < 0.05 for tetrasaccharides or smaller). 28635997 7 28 theme labelling 1171:1179 arg1 approach 1181:1188 A light vs. heavy labelling approach 1153:1188 A light vs. heavy labelling approach 1153:1188 A light vs. heavy labelling approach was employed to compare intact glycan yields from a popular spin-column based approach to the SCF approach. 28635997 10 29 from controls 1878:1885 arg1 samples 1804:1810 blood plasma samples 1791:1810 blood plasma samples from stage III-IV breast cancer patients (n = 20) and age-matched controls (n = 20) 1791:1894 When applied to blood plasma samples from stage III-IV breast cancer patients (n = 20) and age-matched controls (n = 20), the SCF procedure facilitated identification of three glycan nodes with significantly different distributions between the cases and controls (ROC c-statistics > 0.75; p < 0.01). 28635997 1 30 from study 142:146 arg1 1903 162:165 1903 162:165 1903 162:165 Glycan permethylation was introduced as a tool to facilitate the study of glycans in 1903. 28635997 9 31 theme spin 1725:1728 arg1 results 1766:1772 previous spin column-based "glycan node" analysis results 1716:1772 previous spin column-based "glycan node" analysis results 1716:1772 When the SCF procedure was employed upstream to hydrolysis, reduction and acetylation for glycan linkage analysis of pooled glycans from unfractionated blood plasma, analytical reproducibility was on par with that from previous spin column-based "glycan node" analysis results. 28635997 0 32 theme sodium 31:36 arg1 permethylation 61:74 sodium hydroxide-based glycan permethylation 31:74 sodium hydroxide-based glycan permethylation 31:74 A spin column-free approach to sodium hydroxide-based glycan permethylation. 28635997 11 33 theme SCF 2091:2093 arg1 procedure 2110:2118 the SCF permethylation procedure 2087:2118 the SCF permethylation procedure 2087:2118 In summary, the SCF permethylation procedure expedites and economizes both intact glycan analysis and linkage analysis of glycans from whole biospecimens. 28635997 3 34 theme permethylation 443:456 arg1 yields 458:463 decent permethylation yields 436:463 decent permethylation yields on small glycan samples 436:487 Typically, however, either laborious preparation steps or cumbersome and uneconomical spin columns have been needed to obtain decent permethylation yields on small glycan samples. 28635997 3 35 theme spin 396:399 arg1 columns 401:407 cumbersome and uneconomical spin columns 368:407 cumbersome and uneconomical spin columns 368:407 Typically, however, either laborious preparation steps or cumbersome and uneconomical spin columns have been needed to obtain decent permethylation yields on small glycan samples. 28635997 0 36 theme column-free 7:17 arg1 approach 19:26 column-free approach 7:26 column-free approach to sodium hydroxide-based glycan permethylation 7:74 A spin column-free approach to sodium hydroxide-based glycan permethylation. 28635997 9 37 theme analysis 1757:1764 arg1 results 1766:1772 previous spin column-based "glycan node" analysis results 1716:1772 previous spin column-based "glycan node" analysis results 1716:1772 When the SCF procedure was employed upstream to hydrolysis, reduction and acetylation for glycan linkage analysis of pooled glycans from unfractionated blood plasma, analytical reproducibility was on par with that from previous spin column-based "glycan node" analysis results. 28635997 10 38 theme blood 1791:1795 arg1 samples 1804:1810 blood plasma samples 1791:1810 blood plasma samples from stage III-IV breast cancer patients (n = 20) and age-matched controls (n = 20) 1791:1894 When applied to blood plasma samples from stage III-IV breast cancer patients (n = 20) and age-matched controls (n = 20), the SCF procedure facilitated identification of three glycan nodes with significantly different distributions between the cases and controls (ROC c-statistics > 0.75; p < 0.01). 28635997 3 39 theme glycan 474:479 arg1 samples 481:487 small glycan samples 468:487 small glycan samples 468:487 Typically, however, either laborious preparation steps or cumbersome and uneconomical spin columns have been needed to obtain decent permethylation yields on small glycan samples. 28635997 6 40 theme HexNAc 1025:1030 arg1 residues-yields 1039:1053 both hexose (>98%) and HexNAc (>99%) residues-yields 1002:1053 residues-yields 1039:1053 Optimization of the new permethylation procedure provided high permethylation efficiency for both hexose (>98%) and HexNAc (>99%) residues-yields which were comparable to (or better than) those of some widely-used spin column-based procedures. 28635997 6 40 theme HexNAc 1025:1030 arg1 % 1036:1036 >99% 1033:1036 >99% 1033:1036 Optimization of the new permethylation procedure provided high permethylation efficiency for both hexose (>98%) and HexNAc (>99%) residues-yields which were comparable to (or better than) those of some widely-used spin column-based procedures. 28635997 4 41 theme glycan 532:537 arg1 procedure 554:562 a spin column-free (SCF) glycan permethylation procedure 507:562 a spin column-free (SCF) glycan permethylation procedure that is applicable to both O- and N-linked glycans and can be employed upstream to intact glycan analysis by MALDI-MS, ESI-MS, or glycan linkage analysis by GC-MS 507:725 Here we describe a spin column-free (SCF) glycan permethylation procedure that is applicable to both O- and N-linked glycans and can be employed upstream to intact glycan analysis by MALDI-MS, ESI-MS, or glycan linkage analysis by GC-MS. 28635997 4 41 theme glycan 532:537 arg1 applicable 572:581 applicable 572:581 applicable 572:581 Here we describe a spin column-free (SCF) glycan permethylation procedure that is applicable to both O- and N-linked glycans and can be employed upstream to intact glycan analysis by MALDI-MS, ESI-MS, or glycan linkage analysis by GC-MS. 28635997 11 42 from economizes 2134:2143 arg1 biospecimens 2216:2227 whole biospecimens 2210:2227 whole biospecimens 2210:2227 In summary, the SCF permethylation procedure expedites and economizes both intact glycan analysis and linkage analysis of glycans from whole biospecimens. 28635997 8 43 theme p 1376:1376 arg1 < 1378:1378 p < 0.05 1376:1383 p < 0.05 1376:1383 Recovery of intact N-glycans was significantly better with the SCF procedure (p < 0.05), but overall yield of O-glycans was similar or slightly diminished (p < 0.05 for tetrasaccharides or smaller). 28635997 5 44 theme phosphate 797:805 arg1 buffer 807:812 acidified phosphate buffer 787:812 acidified phosphate buffer 787:812 The SCF procedure involves neutralization of NaOH beads by acidified phosphate buffer, which eliminates the risk of glycan oxidative degradation and avoids the use of spin columns. 28635997 7 45 theme spin-column 1250:1260 arg1 approach 1268:1275 a popular spin-column based approach 1240:1275 a popular spin-column based approach to the SCF approach 1240:1295 A light vs. heavy labelling approach was employed to compare intact glycan yields from a popular spin-column based approach to the SCF approach. 28635997 11 46 theme whole 2210:2214 arg1 biospecimens 2216:2227 whole biospecimens 2210:2227 whole biospecimens 2210:2227 In summary, the SCF permethylation procedure expedites and economizes both intact glycan analysis and linkage analysis of glycans from whole biospecimens. 28635997 11 47 from analysis 2164:2171 arg1 biospecimens 2216:2227 whole biospecimens 2210:2227 whole biospecimens 2210:2227 In summary, the SCF permethylation procedure expedites and economizes both intact glycan analysis and linkage analysis of glycans from whole biospecimens. 28635997 2 48 theme permethylation 185:198 arg1 procedures 200:209 permethylation procedures 185:209 permethylation procedures 185:209 Since that time, permethylation procedures have been continually modified to improve permethylation efficiency and qualitative applicability. 28635997 10 49 theme nodes 1958:1962 arg1 identification 1927:1940 identification 1927:1940 identification of three glycan nodes with significantly different distributions between the cases and controls (ROC c-statistics > 0.75; p < 0.01) 1927:2072 When applied to blood plasma samples from stage III-IV breast cancer patients (n = 20) and age-matched controls (n = 20), the SCF procedure facilitated identification of three glycan nodes with significantly different distributions between the cases and controls (ROC c-statistics > 0.75; p < 0.01). 28635997 6 50 dep those 1097:1101 arg1 better 1084:1089 better 1084:1089 better 1084:1089 Optimization of the new permethylation procedure provided high permethylation efficiency for both hexose (>98%) and HexNAc (>99%) residues-yields which were comparable to (or better than) those of some widely-used spin column-based procedures. 28635997 3 51 from yields 458:463 arg1 samples 481:487 small glycan samples 468:487 small glycan samples 468:487 Typically, however, either laborious preparation steps or cumbersome and uneconomical spin columns have been needed to obtain decent permethylation yields on small glycan samples. 28635997 5 52 theme acidified 787:795 arg1 buffer 807:812 acidified phosphate buffer 787:812 acidified phosphate buffer 787:812 The SCF procedure involves neutralization of NaOH beads by acidified phosphate buffer, which eliminates the risk of glycan oxidative degradation and avoids the use of spin columns. 28635997 7 53 theme light 1155:1159 arg1 approach 1181:1188 A light vs. heavy labelling approach 1153:1188 A light vs. heavy labelling approach 1153:1188 A light vs. heavy labelling approach was employed to compare intact glycan yields from a popular spin-column based approach to the SCF approach. 28635997 7 54 theme intact 1214:1219 arg1 yields 1228:1233 intact glycan yields 1214:1233 intact glycan yields 1214:1233 A light vs. heavy labelling approach was employed to compare intact glycan yields from a popular spin-column based approach to the SCF approach. 28635997 4 55 theme O- 591:592 arg1 glycans 607:613 both O- and N-linked glycans 586:613 glycans 607:613 Here we describe a spin column-free (SCF) glycan permethylation procedure that is applicable to both O- and N-linked glycans and can be employed upstream to intact glycan analysis by MALDI-MS, ESI-MS, or glycan linkage analysis by GC-MS. 28635997 10 56 theme breast 1830:1835 arg1 patients 1844:1851 stage III-IV breast cancer patients 1817:1851 stage III-IV breast cancer patients (n = 20) 1817:1860 When applied to blood plasma samples from stage III-IV breast cancer patients (n = 20) and age-matched controls (n = 20), the SCF procedure facilitated identification of three glycan nodes with significantly different distributions between the cases and controls (ROC c-statistics > 0.75; p < 0.01). 28635997 10 56 theme breast 1830:1835 arg1 n 1854:1854 n = 20 1854:1859 n = 20 1854:1859 When applied to blood plasma samples from stage III-IV breast cancer patients (n = 20) and age-matched controls (n = 20), the SCF procedure facilitated identification of three glycan nodes with significantly different distributions between the cases and controls (ROC c-statistics > 0.75; p < 0.01). 28635997 8 57 dep diminished 1442:1451 arg1 < 1456:1456 p < 0.05 1454:1461 p < 0.05 1454:1461 Recovery of intact N-glycans was significantly better with the SCF procedure (p < 0.05), but overall yield of O-glycans was similar or slightly diminished (p < 0.05 for tetrasaccharides or smaller). 28635997 9 58 theme linkage 1594:1600 arg1 analysis 1602:1609 glycan linkage analysis 1587:1609 glycan linkage analysis of pooled glycans from unfractionated blood plasma 1587:1660 When the SCF procedure was employed upstream to hydrolysis, reduction and acetylation for glycan linkage analysis of pooled glycans from unfractionated blood plasma, analytical reproducibility was on par with that from previous spin column-based "glycan node" analysis results. 28635997 11 59 theme glycan 2157:2162 arg1 analysis 2164:2171 intact glycan analysis 2150:2171 intact glycan analysis 2150:2171 In summary, the SCF permethylation procedure expedites and economizes both intact glycan analysis and linkage analysis of glycans from whole biospecimens. 28635997 4 60 theme N-linked 598:605 arg1 glycans 607:613 both O- and N-linked glycans 586:613 glycans 607:613 Here we describe a spin column-free (SCF) glycan permethylation procedure that is applicable to both O- and N-linked glycans and can be employed upstream to intact glycan analysis by MALDI-MS, ESI-MS, or glycan linkage analysis by GC-MS. 28635997 2 61 theme qualitative 283:293 arg1 applicability 295:307 qualitative applicability 283:307 qualitative applicability 283:307 Since that time, permethylation procedures have been continually modified to improve permethylation efficiency and qualitative applicability. 28635997 5 62 theme oxidative 851:859 arg1 degradation 861:871 glycan oxidative degradation 844:871 glycan oxidative degradation 844:871 The SCF procedure involves neutralization of NaOH beads by acidified phosphate buffer, which eliminates the risk of glycan oxidative degradation and avoids the use of spin columns. 28635997 0 63 theme hydroxide-based 38:52 arg1 permethylation 61:74 sodium hydroxide-based glycan permethylation 31:74 sodium hydroxide-based glycan permethylation 31:74 A spin column-free approach to sodium hydroxide-based glycan permethylation. 28635997 6 64 theme column-based 1128:1139 arg1 procedures 1141:1150 some widely-used spin column-based procedures 1106:1150 some widely-used spin column-based procedures 1106:1150 Optimization of the new permethylation procedure provided high permethylation efficiency for both hexose (>98%) and HexNAc (>99%) residues-yields which were comparable to (or better than) those of some widely-used spin column-based procedures. 28635997 8 65 dep better 1345:1350 arg1 < 1378:1378 p < 0.05 1376:1383 p < 0.05 1376:1383 Recovery of intact N-glycans was significantly better with the SCF procedure (p < 0.05), but overall yield of O-glycans was similar or slightly diminished (p < 0.05 for tetrasaccharides or smaller). 28635997 9 66 theme glycans 1621:1627 arg1 analysis 1602:1609 glycan linkage analysis 1587:1609 glycan linkage analysis of pooled glycans from unfractionated blood plasma 1587:1660 When the SCF procedure was employed upstream to hydrolysis, reduction and acetylation for glycan linkage analysis of pooled glycans from unfractionated blood plasma, analytical reproducibility was on par with that from previous spin column-based "glycan node" analysis results. 28635997 6 67 theme widely-used 1111:1121 arg1 procedures 1141:1150 some widely-used spin column-based procedures 1106:1150 some widely-used spin column-based procedures 1106:1150 Optimization of the new permethylation procedure provided high permethylation efficiency for both hexose (>98%) and HexNAc (>99%) residues-yields which were comparable to (or better than) those of some widely-used spin column-based procedures. 28635997 10 68 with nodes 1958:1962 arg1 distributions 1993:2005 significantly different distributions 1969:2005 significantly different distributions between the cases and controls (ROC c-statistics > 0.75; p < 0.01) 1969:2072 When applied to blood plasma samples from stage III-IV breast cancer patients (n = 20) and age-matched controls (n = 20), the SCF procedure facilitated identification of three glycan nodes with significantly different distributions between the cases and controls (ROC c-statistics > 0.75; p < 0.01). 28635997 10 69 from patients 1844:1851 arg1 samples 1804:1810 blood plasma samples 1791:1810 blood plasma samples from stage III-IV breast cancer patients (n = 20) and age-matched controls (n = 20) 1791:1894 When applied to blood plasma samples from stage III-IV breast cancer patients (n = 20) and age-matched controls (n = 20), the SCF procedure facilitated identification of three glycan nodes with significantly different distributions between the cases and controls (ROC c-statistics > 0.75; p < 0.01). 28635997 9 70 from analysis 1602:1609 arg1 plasma 1655:1660 unfractionated blood plasma 1634:1660 unfractionated blood plasma 1634:1660 When the SCF procedure was employed upstream to hydrolysis, reduction and acetylation for glycan linkage analysis of pooled glycans from unfractionated blood plasma, analytical reproducibility was on par with that from previous spin column-based "glycan node" analysis results. 28635997 9 71 theme unfractionated 1634:1647 arg1 plasma 1655:1660 unfractionated blood plasma 1634:1660 unfractionated blood plasma 1634:1660 When the SCF procedure was employed upstream to hydrolysis, reduction and acetylation for glycan linkage analysis of pooled glycans from unfractionated blood plasma, analytical reproducibility was on par with that from previous spin column-based "glycan node" analysis results. 28635997 8 72 theme overall 1391:1397 arg1 yield 1399:1403 overall yield 1391:1403 overall yield of O-glycans 1391:1416 Recovery of intact N-glycans was significantly better with the SCF procedure (p < 0.05), but overall yield of O-glycans was similar or slightly diminished (p < 0.05 for tetrasaccharides or smaller). 28635997 10 73 theme c-statistics 2043:2054 arg1 > 2056:2056 ROC c-statistics > 0.75 2039:2061 ROC c-statistics > 0.75; p < 0.01 2039:2071 When applied to blood plasma samples from stage III-IV breast cancer patients (n = 20) and age-matched controls (n = 20), the SCF procedure facilitated identification of three glycan nodes with significantly different distributions between the cases and controls (ROC c-statistics > 0.75; p < 0.01). 28635997 6 74 theme procedure 948:956 arg1 Optimization 909:920 Optimization 909:920 Optimization of the new permethylation procedure 909:956 Optimization of the new permethylation procedure provided high permethylation efficiency for both hexose (>98%) and HexNAc (>99%) residues-yields which were comparable to (or better than) those of some widely-used spin column-based procedures. 28635997 4 75 theme intact 647:652 arg1 analysis 661:668 intact glycan analysis 647:668 intact glycan analysis 647:668 Here we describe a spin column-free (SCF) glycan permethylation procedure that is applicable to both O- and N-linked glycans and can be employed upstream to intact glycan analysis by MALDI-MS, ESI-MS, or glycan linkage analysis by GC-MS. 28635997 11 76 from analysis 2185:2192 arg1 biospecimens 2216:2227 whole biospecimens 2210:2227 whole biospecimens 2210:2227 In summary, the SCF permethylation procedure expedites and economizes both intact glycan analysis and linkage analysis of glycans from whole biospecimens. 28635997 5 77 theme columns 900:906 arg1 use 888:890 the use 884:890 the use of spin columns 884:906 The SCF procedure involves neutralization of NaOH beads by acidified phosphate buffer, which eliminates the risk of glycan oxidative degradation and avoids the use of spin columns. 28635997 6 78 theme new 929:931 arg1 procedure 948:956 the new permethylation procedure 925:956 the new permethylation procedure 925:956 Optimization of the new permethylation procedure provided high permethylation efficiency for both hexose (>98%) and HexNAc (>99%) residues-yields which were comparable to (or better than) those of some widely-used spin column-based procedures. 28635997 9 79 theme analytical 1663:1672 arg1 reproducibility 1674:1688 analytical reproducibility 1663:1688 analytical reproducibility 1663:1688 When the SCF procedure was employed upstream to hydrolysis, reduction and acetylation for glycan linkage analysis of pooled glycans from unfractionated blood plasma, analytical reproducibility was on par with that from previous spin column-based "glycan node" analysis results. 28635997 10 80 theme stage 1817:1821 arg1 patients 1844:1851 stage III-IV breast cancer patients 1817:1851 stage III-IV breast cancer patients (n = 20) 1817:1860 When applied to blood plasma samples from stage III-IV breast cancer patients (n = 20) and age-matched controls (n = 20), the SCF procedure facilitated identification of three glycan nodes with significantly different distributions between the cases and controls (ROC c-statistics > 0.75; p < 0.01). 28635997 10 80 theme stage 1817:1821 arg1 n 1854:1854 n = 20 1854:1859 n = 20 1854:1859 When applied to blood plasma samples from stage III-IV breast cancer patients (n = 20) and age-matched controls (n = 20), the SCF procedure facilitated identification of three glycan nodes with significantly different distributions between the cases and controls (ROC c-statistics > 0.75; p < 0.01). 28635997 4 81 theme linkage 701:707 arg1 analysis 709:716 glycan linkage analysis 694:716 glycan linkage analysis 694:716 Here we describe a spin column-free (SCF) glycan permethylation procedure that is applicable to both O- and N-linked glycans and can be employed upstream to intact glycan analysis by MALDI-MS, ESI-MS, or glycan linkage analysis by GC-MS. 28635997 10 82 theme SCF 1901:1903 arg1 procedure 1905:1913 the SCF procedure 1897:1913 the SCF procedure 1897:1913 When applied to blood plasma samples from stage III-IV breast cancer patients (n = 20) and age-matched controls (n = 20), the SCF procedure facilitated identification of three glycan nodes with significantly different distributions between the cases and controls (ROC c-statistics > 0.75; p < 0.01). 28635997 11 83 theme permethylation 2095:2108 arg1 procedure 2110:2118 the SCF permethylation procedure 2087:2118 the SCF permethylation procedure 2087:2118 In summary, the SCF permethylation procedure expedites and economizes both intact glycan analysis and linkage analysis of glycans from whole biospecimens. 28635997 9 84 theme previous 1716:1723 arg1 results 1766:1772 previous spin column-based "glycan node" analysis results 1716:1772 previous spin column-based "glycan node" analysis results 1716:1772 When the SCF procedure was employed upstream to hydrolysis, reduction and acetylation for glycan linkage analysis of pooled glycans from unfractionated blood plasma, analytical reproducibility was on par with that from previous spin column-based "glycan node" analysis results. 28635997 6 85 theme high 967:970 arg1 efficiency 987:996 high permethylation efficiency 967:996 high permethylation efficiency for both hexose (>98%) and HexNAc (>99%) residues-yields which were comparable to (or better than) those of some widely-used spin column-based procedures 967:1150 Optimization of the new permethylation procedure provided high permethylation efficiency for both hexose (>98%) and HexNAc (>99%) residues-yields which were comparable to (or better than) those of some widely-used spin column-based procedures. 28635997 1 86 theme glycans 151:157 arg1 study 142:146 the study 138:146 the study of glycans in 1903 138:165 Glycan permethylation was introduced as a tool to facilitate the study of glycans in 1903. 28635997 3 87 theme laborious 337:345 arg1 steps 359:363 laborious preparation steps 337:363 laborious preparation steps 337:363 Typically, however, either laborious preparation steps or cumbersome and uneconomical spin columns have been needed to obtain decent permethylation yields on small glycan samples. 28635997 8 88 theme p 1454:1454 arg1 < 1456:1456 p < 0.05 1454:1461 p < 0.05 1454:1461 Recovery of intact N-glycans was significantly better with the SCF procedure (p < 0.05), but overall yield of O-glycans was similar or slightly diminished (p < 0.05 for tetrasaccharides or smaller). 28635997 7 89 theme heavy 1165:1169 arg1 approach 1181:1188 A light vs. heavy labelling approach 1153:1188 A light vs. heavy labelling approach 1153:1188 A light vs. heavy labelling approach was employed to compare intact glycan yields from a popular spin-column based approach to the SCF approach. 28635997 3 90 theme uneconomical 383:394 arg1 columns 401:407 cumbersome and uneconomical spin columns 368:407 cumbersome and uneconomical spin columns 368:407 Typically, however, either laborious preparation steps or cumbersome and uneconomical spin columns have been needed to obtain decent permethylation yields on small glycan samples. 28635997 5 91 theme SCF 732:734 arg1 procedure 736:744 The SCF procedure 728:744 The SCF procedure 728:744 The SCF procedure involves neutralization of NaOH beads by acidified phosphate buffer, which eliminates the risk of glycan oxidative degradation and avoids the use of spin columns. 28635997 1 92 theme Glycan 77:82 arg1 tool 119:122 a tool 117:122 a tool to facilitate the study of glycans in 1903 117:165 Glycan permethylation was introduced as a tool to facilitate the study of glycans in 1903. 28635997 1 92 theme Glycan 77:82 arg1 permethylation 84:97 Glycan permethylation 77:97 Glycan permethylation 77:97 Glycan permethylation was introduced as a tool to facilitate the study of glycans in 1903. 28635997 11 93 theme glycans 2197:2203 arg1 analysis 2164:2171 intact glycan analysis 2150:2171 intact glycan analysis 2150:2171 In summary, the SCF permethylation procedure expedites and economizes both intact glycan analysis and linkage analysis of glycans from whole biospecimens. 28635997 11 93 theme glycans 2197:2203 arg1 analysis 2185:2192 linkage analysis 2177:2192 linkage analysis 2177:2192 In summary, the SCF permethylation procedure expedites and economizes both intact glycan analysis and linkage analysis of glycans from whole biospecimens. 28635997 11 93 theme glycans 2197:2203 arg1 economizes 2134:2143 economizes 2134:2143 economizes 2134:2143 In summary, the SCF permethylation procedure expedites and economizes both intact glycan analysis and linkage analysis of glycans from whole biospecimens. 28635997 3 94 theme cumbersome 368:377 arg1 columns 401:407 cumbersome and uneconomical spin columns 368:407 cumbersome and uneconomical spin columns 368:407 Typically, however, either laborious preparation steps or cumbersome and uneconomical spin columns have been needed to obtain decent permethylation yields on small glycan samples. 28635997 8 95 theme N-glycans 1317:1325 arg1 Recovery 1298:1305 Recovery 1298:1305 Recovery of intact N-glycans 1298:1325 Recovery of intact N-glycans was significantly better with the SCF procedure (p < 0.05), but overall yield of O-glycans was similar or slightly diminished (p < 0.05 for tetrasaccharides or smaller). 28635997 3 96 theme small 468:472 arg1 samples 481:487 small glycan samples 468:487 small glycan samples 468:487 Typically, however, either laborious preparation steps or cumbersome and uneconomical spin columns have been needed to obtain decent permethylation yields on small glycan samples. 28635997 7 97 theme SCF 1284:1286 arg1 approach 1288:1295 the SCF approach 1280:1295 the SCF approach 1280:1295 A light vs. heavy labelling approach was employed to compare intact glycan yields from a popular spin-column based approach to the SCF approach. 28635997 9 98 theme glycan 1744:1749 arg1 " 1755:1755 column-based "glycan node" 1730:1755 previous spin column-based "glycan node" analysis results 1716:1772 When the SCF procedure was employed upstream to hydrolysis, reduction and acetylation for glycan linkage analysis of pooled glycans from unfractionated blood plasma, analytical reproducibility was on par with that from previous spin column-based "glycan node" analysis results. 28635997 9 99 theme SCF 1506:1508 arg1 procedure 1510:1518 the SCF procedure 1502:1518 the SCF procedure 1502:1518 When the SCF procedure was employed upstream to hydrolysis, reduction and acetylation for glycan linkage analysis of pooled glycans from unfractionated blood plasma, analytical reproducibility was on par with that from previous spin column-based "glycan node" analysis results. 28635997 9 100 theme " 1755:1755 arg1 results 1766:1772 previous spin column-based "glycan node" analysis results 1716:1772 previous spin column-based "glycan node" analysis results 1716:1772 When the SCF procedure was employed upstream to hydrolysis, reduction and acetylation for glycan linkage analysis of pooled glycans from unfractionated blood plasma, analytical reproducibility was on par with that from previous spin column-based "glycan node" analysis results. 28635997 10 101 theme plasma 1797:1802 arg1 samples 1804:1810 blood plasma samples 1791:1810 blood plasma samples from stage III-IV breast cancer patients (n = 20) and age-matched controls (n = 20) 1791:1894 When applied to blood plasma samples from stage III-IV breast cancer patients (n = 20) and age-matched controls (n = 20), the SCF procedure facilitated identification of three glycan nodes with significantly different distributions between the cases and controls (ROC c-statistics > 0.75; p < 0.01). 28635997 11 102 theme linkage 2177:2183 arg1 analysis 2185:2192 linkage analysis 2177:2192 linkage analysis 2177:2192 In summary, the SCF permethylation procedure expedites and economizes both intact glycan analysis and linkage analysis of glycans from whole biospecimens. 28635997 5 103 theme beads 778:782 arg1 neutralization 755:768 neutralization 755:768 neutralization of NaOH beads by acidified phosphate buffer, which eliminates the risk of glycan oxidative degradation and avoids the use of spin columns 755:906 The SCF procedure involves neutralization of NaOH beads by acidified phosphate buffer, which eliminates the risk of glycan oxidative degradation and avoids the use of spin columns. 28635997 7 104 theme based 1262:1266 arg1 approach 1268:1275 a popular spin-column based approach 1240:1275 a popular spin-column based approach to the SCF approach 1240:1295 A light vs. heavy labelling approach was employed to compare intact glycan yields from a popular spin-column based approach to the SCF approach. 28635997 3 105 theme decent 436:441 arg1 yields 458:463 decent permethylation yields 436:463 decent permethylation yields on small glycan samples 436:487 Typically, however, either laborious preparation steps or cumbersome and uneconomical spin columns have been needed to obtain decent permethylation yields on small glycan samples. 28635997 4 106 theme permethylation 539:552 arg1 procedure 554:562 a spin column-free (SCF) glycan permethylation procedure 507:562 a spin column-free (SCF) glycan permethylation procedure that is applicable to both O- and N-linked glycans and can be employed upstream to intact glycan analysis by MALDI-MS, ESI-MS, or glycan linkage analysis by GC-MS 507:725 Here we describe a spin column-free (SCF) glycan permethylation procedure that is applicable to both O- and N-linked glycans and can be employed upstream to intact glycan analysis by MALDI-MS, ESI-MS, or glycan linkage analysis by GC-MS. 28635997 4 106 theme permethylation 539:552 arg1 applicable 572:581 applicable 572:581 applicable 572:581 Here we describe a spin column-free (SCF) glycan permethylation procedure that is applicable to both O- and N-linked glycans and can be employed upstream to intact glycan analysis by MALDI-MS, ESI-MS, or glycan linkage analysis by GC-MS. 28635997 8 107 theme SCF 1361:1363 arg1 procedure 1365:1373 the SCF procedure 1357:1373 the SCF procedure 1357:1373 Recovery of intact N-glycans was significantly better with the SCF procedure (p < 0.05), but overall yield of O-glycans was similar or slightly diminished (p < 0.05 for tetrasaccharides or smaller). 28635997 9 108 theme column-based 1730:1741 arg1 " 1755:1755 column-based "glycan node" 1730:1755 previous spin column-based "glycan node" analysis results 1716:1772 When the SCF procedure was employed upstream to hydrolysis, reduction and acetylation for glycan linkage analysis of pooled glycans from unfractionated blood plasma, analytical reproducibility was on par with that from previous spin column-based "glycan node" analysis results. 28635997 0 109 theme glycan 54:59 arg1 permethylation 61:74 sodium hydroxide-based glycan permethylation 31:74 sodium hydroxide-based glycan permethylation 31:74 A spin column-free approach to sodium hydroxide-based glycan permethylation. 28635997 7 110 theme popular 1242:1248 arg1 approach 1268:1275 a popular spin-column based approach 1240:1275 a popular spin-column based approach to the SCF approach 1240:1295 A light vs. heavy labelling approach was employed to compare intact glycan yields from a popular spin-column based approach to the SCF approach. 28635997 10 111 theme III-IV 1823:1828 arg1 patients 1844:1851 stage III-IV breast cancer patients 1817:1851 stage III-IV breast cancer patients (n = 20) 1817:1860 When applied to blood plasma samples from stage III-IV breast cancer patients (n = 20) and age-matched controls (n = 20), the SCF procedure facilitated identification of three glycan nodes with significantly different distributions between the cases and controls (ROC c-statistics > 0.75; p < 0.01). 28635997 10 111 theme III-IV 1823:1828 arg1 n 1854:1854 n = 20 1854:1859 n = 20 1854:1859 When applied to blood plasma samples from stage III-IV breast cancer patients (n = 20) and age-matched controls (n = 20), the SCF procedure facilitated identification of three glycan nodes with significantly different distributions between the cases and controls (ROC c-statistics > 0.75; p < 0.01). 28635997 4 112 link N-linked 598:605 arg1 glycans 607:613 both O- and N-linked glycans 586:613 glycans 607:613 Here we describe a spin column-free (SCF) glycan permethylation procedure that is applicable to both O- and N-linked glycans and can be employed upstream to intact glycan analysis by MALDI-MS, ESI-MS, or glycan linkage analysis by GC-MS. 28635997 10 113 dep > 2056:2056 arg1 p 2064:2064 p < 0.01 2064:2071 ROC c-statistics > 0.75; p < 0.01 2039:2071 When applied to blood plasma samples from stage III-IV breast cancer patients (n = 20) and age-matched controls (n = 20), the SCF procedure facilitated identification of three glycan nodes with significantly different distributions between the cases and controls (ROC c-statistics > 0.75; p < 0.01). 28635997 11 114 dep economizes 2134:2143 arg1 both 2145:2148 both 2145:2148 both 2145:2148 In summary, the SCF permethylation procedure expedites and economizes both intact glycan analysis and linkage analysis of glycans from whole biospecimens. 28635997 10 115 dep cases 2019:2023 arg1 > 2056:2056 ROC c-statistics > 0.75 2039:2061 ROC c-statistics > 0.75; p < 0.01 2039:2071 When applied to blood plasma samples from stage III-IV breast cancer patients (n = 20) and age-matched controls (n = 20), the SCF procedure facilitated identification of three glycan nodes with significantly different distributions between the cases and controls (ROC c-statistics > 0.75; p < 0.01). 28635997 10 115 dep cases 2019:2023 arg1 the 2015:2017 the 2015:2017 the 2015:2017 When applied to blood plasma samples from stage III-IV breast cancer patients (n = 20) and age-matched controls (n = 20), the SCF procedure facilitated identification of three glycan nodes with significantly different distributions between the cases and controls (ROC c-statistics > 0.75; p < 0.01). 28635997 7 116 theme glycan 1221:1226 arg1 yields 1228:1233 intact glycan yields 1214:1233 intact glycan yields 1214:1233 A light vs. heavy labelling approach was employed to compare intact glycan yields from a popular spin-column based approach to the SCF approach. 28635997 10 117 theme glycan 1951:1956 arg1 nodes 1958:1962 three glycan nodes 1945:1962 three glycan nodes with significantly different distributions between the cases and controls (ROC c-statistics > 0.75; p < 0.01) 1945:2072 When applied to blood plasma samples from stage III-IV breast cancer patients (n = 20) and age-matched controls (n = 20), the SCF procedure facilitated identification of three glycan nodes with significantly different distributions between the cases and controls (ROC c-statistics > 0.75; p < 0.01). 28336715 12 0 theme drug 2289:2292 arg1 effects 2294:2300 adverse drug effects 2281:2300 adverse drug effects 2281:2300 This finding suggests that dynamic processes can be highly vulnerable to drug treatment and should be monitored more rigorously to identify adverse drug effects. 28336715 7 1 theme surface-mediated 1217:1232 arg1 processes 1234:1242 cell surface-mediated processes 1212:1242 cell surface-mediated processes 1212:1242 Primary cells displayed distinct expression of surface markers and transporters underpinning the importance of carefully validating model cell lines selected for the study of cell surface-mediated processes. 28336715 5 2 link N-linked 768:775 arg1 glycoproteomes 790:803 the N-linked cell-surface glycoproteomes 764:803 the N-linked cell-surface glycoproteomes of 15 standard laboratory human cell lines and three primary lymphocytic cell types 764:887 To benchmark this workflow and to provide guidance for cell line selection for functional experiments, we generated an inventory of the N-linked cell-surface glycoproteomes of 15 standard laboratory human cell lines and three primary lymphocytic cell types. 28336715 7 3 theme cell 1212:1215 arg1 processes 1234:1242 cell surface-mediated processes 1212:1242 cell surface-mediated processes 1212:1242 Primary cells displayed distinct expression of surface markers and transporters underpinning the importance of carefully validating model cell lines selected for the study of cell surface-mediated processes. 28336715 10 4 theme surface 1748:1754 arg1 phases 1734:1739 three distinct phases 1719:1739 three distinct phases: rapid surface presentation and secretion of proteins 1719:1793 Time-dependent changes observed in membrane protein presentation reflect functional remodeling during the phenotypic transition in three distinct phases: rapid surface presentation and secretion of proteins from intracellular pools concurrent with rapid internalization of no longer needed proteins and finally delayed presentation of newly synthesized macrophage markers. 28336715 10 4 theme surface 1748:1754 arg1 presentation 1756:1767 rapid surface presentation 1742:1767 rapid surface presentation 1742:1767 Time-dependent changes observed in membrane protein presentation reflect functional remodeling during the phenotypic transition in three distinct phases: rapid surface presentation and secretion of proteins from intracellular pools concurrent with rapid internalization of no longer needed proteins and finally delayed presentation of newly synthesized macrophage markers. 28336715 5 5 theme N-linked 768:775 arg1 glycoproteomes 790:803 the N-linked cell-surface glycoproteomes 764:803 the N-linked cell-surface glycoproteomes of 15 standard laboratory human cell lines and three primary lymphocytic cell types 764:887 To benchmark this workflow and to provide guidance for cell line selection for functional experiments, we generated an inventory of the N-linked cell-surface glycoproteomes of 15 standard laboratory human cell lines and three primary lymphocytic cell types. 28336715 9 6 theme adherent 1572:1579 arg1 cells 1581:1585 macrophage-like adherent cells 1556:1585 macrophage-like adherent cells 1556:1585 This enabled the time-resolved analysis of plasma membrane protein presentation during differentiation of the monocytic suspension cell line THP-1 into macrophage-like adherent cells. 28336715 10 7 theme rapid 1836:1840 arg1 internalization 1842:1856 rapid internalization 1836:1856 rapid internalization of no longer needed proteins 1836:1885 Time-dependent changes observed in membrane protein presentation reflect functional remodeling during the phenotypic transition in three distinct phases: rapid surface presentation and secretion of proteins from intracellular pools concurrent with rapid internalization of no longer needed proteins and finally delayed presentation of newly synthesized macrophage markers. 28336715 5 8 theme line 692:695 arg1 selection 697:705 cell line selection 687:705 cell line selection 687:705 To benchmark this workflow and to provide guidance for cell line selection for functional experiments, we generated an inventory of the N-linked cell-surface glycoproteomes of 15 standard laboratory human cell lines and three primary lymphocytic cell types. 28336715 10 9 theme markers 1952:1958 arg1 internalization 1842:1856 rapid internalization 1836:1856 rapid internalization of no longer needed proteins 1836:1885 Time-dependent changes observed in membrane protein presentation reflect functional remodeling during the phenotypic transition in three distinct phases: rapid surface presentation and secretion of proteins from intracellular pools concurrent with rapid internalization of no longer needed proteins and finally delayed presentation of newly synthesized macrophage markers. 28336715 10 9 theme markers 1952:1958 arg1 presentation 1907:1918 finally delayed presentation 1891:1918 finally delayed presentation of newly synthesized macrophage markers 1891:1958 Time-dependent changes observed in membrane protein presentation reflect functional remodeling during the phenotypic transition in three distinct phases: rapid surface presentation and secretion of proteins from intracellular pools concurrent with rapid internalization of no longer needed proteins and finally delayed presentation of newly synthesized macrophage markers. 28336715 1 10 theme intracellular 202:214 arg1 signaling 216:224 intracellular signaling 202:224 intracellular signaling 202:224 The plasma membrane proteome plays a crucial role in inter- and intracellular signaling, cell survival, and cell identity. 28336715 8 11 theme proteome 1292:1299 arg1 changes 1264:1270 dynamic changes 1256:1270 dynamic changes of the cell-surface proteome in a highly multiplexed experiment 1256:1334 To monitor dynamic changes of the cell-surface proteome in a highly multiplexed experiment, we employed an isobaric mass tag-based chemical labeling strategy. 28336715 10 12 from pools 1814:1818 arg1 transition 1705:1714 the phenotypic transition 1690:1714 the phenotypic transition in three distinct phases: rapid surface presentation and secretion of proteins from intracellular pools concurrent with rapid internalization of no longer needed proteins and finally delayed presentation of newly synthesized macrophage markers 1690:1958 Time-dependent changes observed in membrane protein presentation reflect functional remodeling during the phenotypic transition in three distinct phases: rapid surface presentation and secretion of proteins from intracellular pools concurrent with rapid internalization of no longer needed proteins and finally delayed presentation of newly synthesized macrophage markers. 28336715 8 13 theme isobaric 1352:1359 arg1 strategy 1394:1401 an isobaric mass tag-based chemical labeling strategy 1349:1401 an isobaric mass tag-based chemical labeling strategy 1349:1401 To monitor dynamic changes of the cell-surface proteome in a highly multiplexed experiment, we employed an isobaric mass tag-based chemical labeling strategy. 28336715 11 14 theme kinase 2023:2028 arg1 inhibitors 2030:2039 marketed receptor tyrosine kinase inhibitors 1996:2039 marketed receptor tyrosine kinase inhibitors 1996:2039 Perturbation of this process using marketed receptor tyrosine kinase inhibitors revealed dasatinib to severely compromise macrophage differentiation due to an off-target activity. 28336715 8 15 theme tag-based 1366:1374 arg1 strategy 1394:1401 an isobaric mass tag-based chemical labeling strategy 1349:1401 an isobaric mass tag-based chemical labeling strategy 1349:1401 To monitor dynamic changes of the cell-surface proteome in a highly multiplexed experiment, we employed an isobaric mass tag-based chemical labeling strategy. 28336715 11 16 theme receptor 2005:2012 arg1 kinase 2023:2028 receptor tyrosine kinase 2005:2028 marketed receptor tyrosine kinase inhibitors 1996:2039 Perturbation of this process using marketed receptor tyrosine kinase inhibitors revealed dasatinib to severely compromise macrophage differentiation due to an off-target activity. 28336715 7 17 theme cell 1175:1178 arg1 lines 1180:1184 carefully validating model cell lines 1148:1184 carefully validating model cell lines selected for the study of cell surface-mediated processes 1148:1242 Primary cells displayed distinct expression of surface markers and transporters underpinning the importance of carefully validating model cell lines selected for the study of cell surface-mediated processes. 28336715 2 18 theme pharmacological 299:313 arg1 intervention 315:326 pharmacological intervention 299:326 pharmacological intervention 299:326 As such, it is a prominent target for pharmacological intervention. 28336715 8 19 theme multiplexed 1313:1323 arg1 experiment 1325:1334 a highly multiplexed experiment 1304:1334 a highly multiplexed experiment 1304:1334 To monitor dynamic changes of the cell-surface proteome in a highly multiplexed experiment, we employed an isobaric mass tag-based chemical labeling strategy. 28336715 8 20 theme labeling 1385:1392 arg1 strategy 1394:1401 an isobaric mass tag-based chemical labeling strategy 1349:1401 an isobaric mass tag-based chemical labeling strategy 1349:1401 To monitor dynamic changes of the cell-surface proteome in a highly multiplexed experiment, we employed an isobaric mass tag-based chemical labeling strategy. 28336715 7 21 theme validating 1158:1167 arg1 lines 1180:1184 carefully validating model cell lines 1148:1184 carefully validating model cell lines selected for the study of cell surface-mediated processes 1148:1242 Primary cells displayed distinct expression of surface markers and transporters underpinning the importance of carefully validating model cell lines selected for the study of cell surface-mediated processes. 28336715 7 22 theme surface 1084:1090 arg1 markers 1092:1098 surface markers 1084:1098 surface markers 1084:1098 Primary cells displayed distinct expression of surface markers and transporters underpinning the importance of carefully validating model cell lines selected for the study of cell surface-mediated processes. 28336715 3 23 from abundance 348:356 arg1 conjunction 381:391 conjunction 381:391 conjunction with challenging extractability and solubility 381:438 The relatively low abundance of this subproteome in conjunction with challenging extractability and solubility still hampers its comprehensive analysis. 28336715 5 24 theme cell 837:840 arg1 lines 842:846 15 standard laboratory human cell lines 808:846 15 standard laboratory human cell lines 808:846 To benchmark this workflow and to provide guidance for cell line selection for functional experiments, we generated an inventory of the N-linked cell-surface glycoproteomes of 15 standard laboratory human cell lines and three primary lymphocytic cell types. 28336715 4 25 theme mass 546:549 arg1 spectrometry 551:562 mass spectrometry 546:562 mass spectrometry 546:562 Here, we combined a chemical glycoprotein-tagging strategy with mass spectrometry to enable comprehensive analysis of the cell-surface glycoproteome. 28336715 7 26 theme Primary 1037:1043 arg1 cells 1045:1049 Primary cells 1037:1049 Primary cells 1037:1049 Primary cells displayed distinct expression of surface markers and transporters underpinning the importance of carefully validating model cell lines selected for the study of cell surface-mediated processes. 28336715 4 27 theme chemical 502:509 arg1 strategy 532:539 a chemical glycoprotein-tagging strategy 500:539 a chemical glycoprotein-tagging strategy with mass spectrometry 500:562 Here, we combined a chemical glycoprotein-tagging strategy with mass spectrometry to enable comprehensive analysis of the cell-surface glycoproteome. 28336715 10 28 theme protein 1632:1638 arg1 presentation 1640:1651 membrane protein presentation 1623:1651 membrane protein presentation 1623:1651 Time-dependent changes observed in membrane protein presentation reflect functional remodeling during the phenotypic transition in three distinct phases: rapid surface presentation and secretion of proteins from intracellular pools concurrent with rapid internalization of no longer needed proteins and finally delayed presentation of newly synthesized macrophage markers. 28336715 5 29 theme laboratory 820:829 arg1 lines 842:846 15 standard laboratory human cell lines 808:846 15 standard laboratory human cell lines 808:846 To benchmark this workflow and to provide guidance for cell line selection for functional experiments, we generated an inventory of the N-linked cell-surface glycoproteomes of 15 standard laboratory human cell lines and three primary lymphocytic cell types. 28336715 3 30 theme comprehensive 458:470 arg1 analysis 472:479 its comprehensive analysis 454:479 its comprehensive analysis 454:479 The relatively low abundance of this subproteome in conjunction with challenging extractability and solubility still hampers its comprehensive analysis. 28336715 9 31 theme plasma 1447:1452 arg1 presentation 1471:1482 plasma membrane protein presentation 1447:1482 plasma membrane protein presentation 1447:1482 This enabled the time-resolved analysis of plasma membrane protein presentation during differentiation of the monocytic suspension cell line THP-1 into macrophage-like adherent cells. 28336715 4 32 theme cell-surface 604:615 arg1 glycoproteome 617:629 the cell-surface glycoproteome 600:629 the cell-surface glycoproteome 600:629 Here, we combined a chemical glycoprotein-tagging strategy with mass spectrometry to enable comprehensive analysis of the cell-surface glycoproteome. 28336715 10 33 theme proteins 1878:1885 arg1 internalization 1842:1856 rapid internalization 1836:1856 rapid internalization of no longer needed proteins 1836:1885 Time-dependent changes observed in membrane protein presentation reflect functional remodeling during the phenotypic transition in three distinct phases: rapid surface presentation and secretion of proteins from intracellular pools concurrent with rapid internalization of no longer needed proteins and finally delayed presentation of newly synthesized macrophage markers. 28336715 10 33 theme proteins 1878:1885 arg1 presentation 1907:1918 finally delayed presentation 1891:1918 finally delayed presentation of newly synthesized macrophage markers 1891:1958 Time-dependent changes observed in membrane protein presentation reflect functional remodeling during the phenotypic transition in three distinct phases: rapid surface presentation and secretion of proteins from intracellular pools concurrent with rapid internalization of no longer needed proteins and finally delayed presentation of newly synthesized macrophage markers. 28336715 0 34 theme N-Glycoproteome 24:38 arg1 Dynamics 40:47 Cell-surface N-Glycoproteome Dynamics 11:47 Cell-surface N-Glycoproteome Dynamics 11:47 Monitoring Cell-surface N-Glycoproteome Dynamics by Quantitative Proteomics Reveals Mechanistic Insights into Macrophage Differentiation. 28336715 9 35 theme protein 1463:1469 arg1 presentation 1471:1482 plasma membrane protein presentation 1447:1482 plasma membrane protein presentation 1447:1482 This enabled the time-resolved analysis of plasma membrane protein presentation during differentiation of the monocytic suspension cell line THP-1 into macrophage-like adherent cells. 28336715 1 36 theme plasma 142:147 arg1 proteome 158:165 The plasma membrane proteome 138:165 The plasma membrane proteome 138:165 The plasma membrane proteome plays a crucial role in inter- and intracellular signaling, cell survival, and cell identity. 28336715 5 37 theme primary 858:864 arg1 types 883:887 three primary lymphocytic cell types 852:887 three primary lymphocytic cell types 852:887 To benchmark this workflow and to provide guidance for cell line selection for functional experiments, we generated an inventory of the N-linked cell-surface glycoproteomes of 15 standard laboratory human cell lines and three primary lymphocytic cell types. 28336715 4 38 theme comprehensive 574:586 arg1 analysis 588:595 comprehensive analysis 574:595 comprehensive analysis of the cell-surface glycoproteome 574:629 Here, we combined a chemical glycoprotein-tagging strategy with mass spectrometry to enable comprehensive analysis of the cell-surface glycoproteome. 28336715 0 39 theme Mechanistic 84:94 arg1 Insights 96:103 Mechanistic Insights 84:103 Mechanistic Insights into Macrophage Differentiation 84:135 Monitoring Cell-surface N-Glycoproteome Dynamics by Quantitative Proteomics Reveals Mechanistic Insights into Macrophage Differentiation. 28336715 5 40 theme cell 878:881 arg1 types 883:887 three primary lymphocytic cell types 852:887 three primary lymphocytic cell types 852:887 To benchmark this workflow and to provide guidance for cell line selection for functional experiments, we generated an inventory of the N-linked cell-surface glycoproteomes of 15 standard laboratory human cell lines and three primary lymphocytic cell types. 28336715 6 41 theme plasma 912:917 arg1 membrane 919:926 about 900 plasma membrane 902:926 about 900 plasma membrane 902:926 On average, about 900 plasma membrane and secreted proteins were identified per experiment, including more than 300 transporters and ion channels. 28336715 9 42 theme monocytic 1514:1522 arg1 THP-1 1545:1549 the monocytic suspension cell line THP-1 1510:1549 the monocytic suspension cell line THP-1 1510:1549 This enabled the time-resolved analysis of plasma membrane protein presentation during differentiation of the monocytic suspension cell line THP-1 into macrophage-like adherent cells. 28336715 8 43 from changes 1264:1270 arg1 experiment 1325:1334 a highly multiplexed experiment 1304:1334 a highly multiplexed experiment 1304:1334 To monitor dynamic changes of the cell-surface proteome in a highly multiplexed experiment, we employed an isobaric mass tag-based chemical labeling strategy. 28336715 10 44 theme macrophage 1941:1950 arg1 markers 1952:1958 newly synthesized macrophage markers 1923:1958 newly synthesized macrophage markers 1923:1958 Time-dependent changes observed in membrane protein presentation reflect functional remodeling during the phenotypic transition in three distinct phases: rapid surface presentation and secretion of proteins from intracellular pools concurrent with rapid internalization of no longer needed proteins and finally delayed presentation of newly synthesized macrophage markers. 28336715 9 45 theme cell 1535:1538 arg1 THP-1 1545:1549 the monocytic suspension cell line THP-1 1510:1549 the monocytic suspension cell line THP-1 1510:1549 This enabled the time-resolved analysis of plasma membrane protein presentation during differentiation of the monocytic suspension cell line THP-1 into macrophage-like adherent cells. 28336715 5 46 theme lymphocytic 866:876 arg1 types 883:887 three primary lymphocytic cell types 852:887 three primary lymphocytic cell types 852:887 To benchmark this workflow and to provide guidance for cell line selection for functional experiments, we generated an inventory of the N-linked cell-surface glycoproteomes of 15 standard laboratory human cell lines and three primary lymphocytic cell types. 28336715 10 47 with concurrent 1820:1829 arg1 internalization 1842:1856 rapid internalization 1836:1856 rapid internalization of no longer needed proteins 1836:1885 Time-dependent changes observed in membrane protein presentation reflect functional remodeling during the phenotypic transition in three distinct phases: rapid surface presentation and secretion of proteins from intracellular pools concurrent with rapid internalization of no longer needed proteins and finally delayed presentation of newly synthesized macrophage markers. 28336715 10 47 with concurrent 1820:1829 arg1 presentation 1907:1918 finally delayed presentation 1891:1918 finally delayed presentation of newly synthesized macrophage markers 1891:1958 Time-dependent changes observed in membrane protein presentation reflect functional remodeling during the phenotypic transition in three distinct phases: rapid surface presentation and secretion of proteins from intracellular pools concurrent with rapid internalization of no longer needed proteins and finally delayed presentation of newly synthesized macrophage markers. 28336715 5 48 theme lines 842:846 arg1 glycoproteomes 790:803 the N-linked cell-surface glycoproteomes 764:803 the N-linked cell-surface glycoproteomes of 15 standard laboratory human cell lines and three primary lymphocytic cell types 764:887 To benchmark this workflow and to provide guidance for cell line selection for functional experiments, we generated an inventory of the N-linked cell-surface glycoproteomes of 15 standard laboratory human cell lines and three primary lymphocytic cell types. 28336715 5 49 theme functional 711:720 arg1 experiments 722:732 functional experiments 711:732 functional experiments 711:732 To benchmark this workflow and to provide guidance for cell line selection for functional experiments, we generated an inventory of the N-linked cell-surface glycoproteomes of 15 standard laboratory human cell lines and three primary lymphocytic cell types. 28336715 9 50 theme THP-1 1545:1549 arg1 differentiation 1491:1505 differentiation 1491:1505 differentiation of the monocytic suspension cell line THP-1 into macrophage-like adherent cells 1491:1585 This enabled the time-resolved analysis of plasma membrane protein presentation during differentiation of the monocytic suspension cell line THP-1 into macrophage-like adherent cells. 28336715 12 51 theme adverse 2281:2287 arg1 effects 2294:2300 adverse drug effects 2281:2300 adverse drug effects 2281:2300 This finding suggests that dynamic processes can be highly vulnerable to drug treatment and should be monitored more rigorously to identify adverse drug effects. 28336715 9 52 theme macrophage-like 1556:1570 arg1 cells 1581:1585 macrophage-like adherent cells 1556:1585 macrophage-like adherent cells 1556:1585 This enabled the time-resolved analysis of plasma membrane protein presentation during differentiation of the monocytic suspension cell line THP-1 into macrophage-like adherent cells. 28336715 8 53 theme dynamic 1256:1262 arg1 changes 1264:1270 dynamic changes 1256:1270 dynamic changes of the cell-surface proteome in a highly multiplexed experiment 1256:1334 To monitor dynamic changes of the cell-surface proteome in a highly multiplexed experiment, we employed an isobaric mass tag-based chemical labeling strategy. 28336715 10 54 theme rapid 1742:1746 arg1 phases 1734:1739 three distinct phases 1719:1739 three distinct phases: rapid surface presentation and secretion of proteins 1719:1793 Time-dependent changes observed in membrane protein presentation reflect functional remodeling during the phenotypic transition in three distinct phases: rapid surface presentation and secretion of proteins from intracellular pools concurrent with rapid internalization of no longer needed proteins and finally delayed presentation of newly synthesized macrophage markers. 28336715 10 54 theme rapid 1742:1746 arg1 presentation 1756:1767 rapid surface presentation 1742:1767 rapid surface presentation 1742:1767 Time-dependent changes observed in membrane protein presentation reflect functional remodeling during the phenotypic transition in three distinct phases: rapid surface presentation and secretion of proteins from intracellular pools concurrent with rapid internalization of no longer needed proteins and finally delayed presentation of newly synthesized macrophage markers. 28336715 5 55 theme cell 687:690 arg1 selection 697:705 cell line selection 687:705 cell line selection 687:705 To benchmark this workflow and to provide guidance for cell line selection for functional experiments, we generated an inventory of the N-linked cell-surface glycoproteomes of 15 standard laboratory human cell lines and three primary lymphocytic cell types. 28336715 2 56 theme prominent 278:286 arg1 target 288:293 a prominent target 276:293 a prominent target for pharmacological intervention 276:326 As such, it is a prominent target for pharmacological intervention. 28336715 2 56 theme prominent 278:286 arg1 it 270:271 it 270:271 it 270:271 As such, it is a prominent target for pharmacological intervention. 28336715 10 57 located observed 1611:1618 arg1 presentation 1640:1651 membrane protein presentation 1623:1651 membrane protein presentation 1623:1651 Time-dependent changes observed in membrane protein presentation reflect functional remodeling during the phenotypic transition in three distinct phases: rapid surface presentation and secretion of proteins from intracellular pools concurrent with rapid internalization of no longer needed proteins and finally delayed presentation of newly synthesized macrophage markers. 28336715 10 57 located observed 1611:1618 arg2 changes 1603:1609 Time-dependent changes 1588:1609 Time-dependent changes observed in membrane protein presentation 1588:1651 Time-dependent changes observed in membrane protein presentation reflect functional remodeling during the phenotypic transition in three distinct phases: rapid surface presentation and secretion of proteins from intracellular pools concurrent with rapid internalization of no longer needed proteins and finally delayed presentation of newly synthesized macrophage markers. 28336715 12 58 theme drug 2214:2217 arg1 treatment 2219:2227 drug treatment 2214:2227 drug treatment 2214:2227 This finding suggests that dynamic processes can be highly vulnerable to drug treatment and should be monitored more rigorously to identify adverse drug effects. 28336715 10 59 theme proteins 1786:1793 arg1 phases 1734:1739 three distinct phases 1719:1739 three distinct phases: rapid surface presentation and secretion of proteins 1719:1793 Time-dependent changes observed in membrane protein presentation reflect functional remodeling during the phenotypic transition in three distinct phases: rapid surface presentation and secretion of proteins from intracellular pools concurrent with rapid internalization of no longer needed proteins and finally delayed presentation of newly synthesized macrophage markers. 28336715 10 59 theme proteins 1786:1793 arg1 secretion 1773:1781 secretion 1773:1781 secretion of proteins 1773:1793 Time-dependent changes observed in membrane protein presentation reflect functional remodeling during the phenotypic transition in three distinct phases: rapid surface presentation and secretion of proteins from intracellular pools concurrent with rapid internalization of no longer needed proteins and finally delayed presentation of newly synthesized macrophage markers. 28336715 10 59 theme proteins 1786:1793 arg1 presentation 1756:1767 rapid surface presentation 1742:1767 rapid surface presentation 1742:1767 Time-dependent changes observed in membrane protein presentation reflect functional remodeling during the phenotypic transition in three distinct phases: rapid surface presentation and secretion of proteins from intracellular pools concurrent with rapid internalization of no longer needed proteins and finally delayed presentation of newly synthesized macrophage markers. 28336715 7 60 theme lines 1180:1184 arg1 importance 1134:1143 the importance 1130:1143 the importance of carefully validating model cell lines selected for the study of cell surface-mediated processes 1130:1242 Primary cells displayed distinct expression of surface markers and transporters underpinning the importance of carefully validating model cell lines selected for the study of cell surface-mediated processes. 28336715 8 61 theme cell-surface 1279:1290 arg1 proteome 1292:1299 the cell-surface proteome 1275:1299 the cell-surface proteome 1275:1299 To monitor dynamic changes of the cell-surface proteome in a highly multiplexed experiment, we employed an isobaric mass tag-based chemical labeling strategy. 28336715 7 62 theme model 1169:1173 arg1 lines 1180:1184 carefully validating model cell lines 1148:1184 carefully validating model cell lines selected for the study of cell surface-mediated processes 1148:1242 Primary cells displayed distinct expression of surface markers and transporters underpinning the importance of carefully validating model cell lines selected for the study of cell surface-mediated processes. 28336715 1 63 theme cell 227:230 arg1 survival 232:239 cell survival 227:239 cell survival 227:239 The plasma membrane proteome plays a crucial role in inter- and intracellular signaling, cell survival, and cell identity. 28336715 8 64 theme mass 1361:1364 arg1 strategy 1394:1401 an isobaric mass tag-based chemical labeling strategy 1349:1401 an isobaric mass tag-based chemical labeling strategy 1349:1401 To monitor dynamic changes of the cell-surface proteome in a highly multiplexed experiment, we employed an isobaric mass tag-based chemical labeling strategy. 28336715 10 65 theme concurrent 1820:1829 arg1 pools 1814:1818 intracellular pools 1800:1818 intracellular pools concurrent with rapid internalization of no longer needed proteins and finally delayed presentation of newly synthesized macrophage markers 1800:1958 Time-dependent changes observed in membrane protein presentation reflect functional remodeling during the phenotypic transition in three distinct phases: rapid surface presentation and secretion of proteins from intracellular pools concurrent with rapid internalization of no longer needed proteins and finally delayed presentation of newly synthesized macrophage markers. 28336715 11 66 theme tyrosine 2014:2021 arg1 kinase 2023:2028 receptor tyrosine kinase 2005:2028 marketed receptor tyrosine kinase inhibitors 1996:2039 Perturbation of this process using marketed receptor tyrosine kinase inhibitors revealed dasatinib to severely compromise macrophage differentiation due to an off-target activity. 28336715 5 67 theme cell-surface 777:788 arg1 glycoproteomes 790:803 the N-linked cell-surface glycoproteomes 764:803 the N-linked cell-surface glycoproteomes of 15 standard laboratory human cell lines and three primary lymphocytic cell types 764:887 To benchmark this workflow and to provide guidance for cell line selection for functional experiments, we generated an inventory of the N-linked cell-surface glycoproteomes of 15 standard laboratory human cell lines and three primary lymphocytic cell types. 28336715 6 68 theme ion 1023:1025 arg1 channels 1027:1034 ion channels 1023:1034 ion channels 1023:1034 On average, about 900 plasma membrane and secreted proteins were identified per experiment, including more than 300 transporters and ion channels. 28336715 8 69 theme chemical 1376:1383 arg1 labeling 1385:1392 chemical labeling 1376:1392 an isobaric mass tag-based chemical labeling strategy 1349:1401 To monitor dynamic changes of the cell-surface proteome in a highly multiplexed experiment, we employed an isobaric mass tag-based chemical labeling strategy. 28336715 10 70 theme intracellular 1800:1812 arg1 pools 1814:1818 intracellular pools 1800:1818 intracellular pools concurrent with rapid internalization of no longer needed proteins and finally delayed presentation of newly synthesized macrophage markers 1800:1958 Time-dependent changes observed in membrane protein presentation reflect functional remodeling during the phenotypic transition in three distinct phases: rapid surface presentation and secretion of proteins from intracellular pools concurrent with rapid internalization of no longer needed proteins and finally delayed presentation of newly synthesized macrophage markers. 28336715 7 71 theme transporters 1104:1115 arg1 expression 1070:1079 distinct expression 1061:1079 distinct expression of surface markers and transporters underpinning the importance of carefully validating model cell lines selected for the study of cell surface-mediated processes 1061:1242 Primary cells displayed distinct expression of surface markers and transporters underpinning the importance of carefully validating model cell lines selected for the study of cell surface-mediated processes. 28336715 1 72 theme membrane 149:156 arg1 proteome 158:165 The plasma membrane proteome 138:165 The plasma membrane proteome 138:165 The plasma membrane proteome plays a crucial role in inter- and intracellular signaling, cell survival, and cell identity. 28336715 10 73 theme synthesized 1929:1939 arg1 markers 1952:1958 newly synthesized macrophage markers 1923:1958 newly synthesized macrophage markers 1923:1958 Time-dependent changes observed in membrane protein presentation reflect functional remodeling during the phenotypic transition in three distinct phases: rapid surface presentation and secretion of proteins from intracellular pools concurrent with rapid internalization of no longer needed proteins and finally delayed presentation of newly synthesized macrophage markers. 28336715 10 74 dep phases 1734:1739 arg1 phases 1734:1739 three distinct phases 1719:1739 three distinct phases: rapid surface presentation and secretion of proteins 1719:1793 Time-dependent changes observed in membrane protein presentation reflect functional remodeling during the phenotypic transition in three distinct phases: rapid surface presentation and secretion of proteins from intracellular pools concurrent with rapid internalization of no longer needed proteins and finally delayed presentation of newly synthesized macrophage markers. 28336715 10 74 dep phases 1734:1739 arg1 secretion 1773:1781 secretion 1773:1781 secretion of proteins 1773:1793 Time-dependent changes observed in membrane protein presentation reflect functional remodeling during the phenotypic transition in three distinct phases: rapid surface presentation and secretion of proteins from intracellular pools concurrent with rapid internalization of no longer needed proteins and finally delayed presentation of newly synthesized macrophage markers. 28336715 10 74 dep phases 1734:1739 arg1 presentation 1756:1767 rapid surface presentation 1742:1767 rapid surface presentation 1742:1767 Time-dependent changes observed in membrane protein presentation reflect functional remodeling during the phenotypic transition in three distinct phases: rapid surface presentation and secretion of proteins from intracellular pools concurrent with rapid internalization of no longer needed proteins and finally delayed presentation of newly synthesized macrophage markers. 28336715 7 75 theme markers 1092:1098 arg1 expression 1070:1079 distinct expression 1061:1079 distinct expression of surface markers and transporters underpinning the importance of carefully validating model cell lines selected for the study of cell surface-mediated processes 1061:1242 Primary cells displayed distinct expression of surface markers and transporters underpinning the importance of carefully validating model cell lines selected for the study of cell surface-mediated processes. 28336715 5 76 theme human 831:835 arg1 lines 842:846 15 standard laboratory human cell lines 808:846 15 standard laboratory human cell lines 808:846 To benchmark this workflow and to provide guidance for cell line selection for functional experiments, we generated an inventory of the N-linked cell-surface glycoproteomes of 15 standard laboratory human cell lines and three primary lymphocytic cell types. 28336715 1 77 theme crucial 175:181 arg1 role 183:186 a crucial role 173:186 a crucial role 173:186 The plasma membrane proteome plays a crucial role in inter- and intracellular signaling, cell survival, and cell identity. 28336715 1 78 theme cell 246:249 arg1 identity 251:258 cell identity 246:258 cell identity 246:258 The plasma membrane proteome plays a crucial role in inter- and intracellular signaling, cell survival, and cell identity. 28336715 0 79 theme Macrophage 110:119 arg1 Differentiation 121:135 Macrophage Differentiation 110:135 Macrophage Differentiation 110:135 Monitoring Cell-surface N-Glycoproteome Dynamics by Quantitative Proteomics Reveals Mechanistic Insights into Macrophage Differentiation. 28336715 12 80 theme dynamic 2168:2174 arg1 processes 2176:2184 dynamic processes 2168:2184 dynamic processes 2168:2184 This finding suggests that dynamic processes can be highly vulnerable to drug treatment and should be monitored more rigorously to identify adverse drug effects. 28336715 7 81 theme distinct 1061:1068 arg1 expression 1070:1079 distinct expression 1061:1079 distinct expression of surface markers and transporters underpinning the importance of carefully validating model cell lines selected for the study of cell surface-mediated processes 1061:1242 Primary cells displayed distinct expression of surface markers and transporters underpinning the importance of carefully validating model cell lines selected for the study of cell surface-mediated processes. 28336715 3 82 theme low 344:346 arg1 abundance 348:356 The relatively low abundance 329:356 The relatively low abundance of this subproteome in conjunction with challenging extractability and solubility 329:438 The relatively low abundance of this subproteome in conjunction with challenging extractability and solubility still hampers its comprehensive analysis. 28336715 10 83 theme Time-dependent 1588:1601 arg1 changes 1603:1609 Time-dependent changes 1588:1609 Time-dependent changes observed in membrane protein presentation 1588:1651 Time-dependent changes observed in membrane protein presentation reflect functional remodeling during the phenotypic transition in three distinct phases: rapid surface presentation and secretion of proteins from intracellular pools concurrent with rapid internalization of no longer needed proteins and finally delayed presentation of newly synthesized macrophage markers. 28336715 11 84 theme marketed 1996:2003 arg1 inhibitors 2030:2039 marketed receptor tyrosine kinase inhibitors 1996:2039 marketed receptor tyrosine kinase inhibitors 1996:2039 Perturbation of this process using marketed receptor tyrosine kinase inhibitors revealed dasatinib to severely compromise macrophage differentiation due to an off-target activity. 28336715 10 85 from transition 1705:1714 arg1 phases 1734:1739 three distinct phases 1719:1739 three distinct phases: rapid surface presentation and secretion of proteins 1719:1793 Time-dependent changes observed in membrane protein presentation reflect functional remodeling during the phenotypic transition in three distinct phases: rapid surface presentation and secretion of proteins from intracellular pools concurrent with rapid internalization of no longer needed proteins and finally delayed presentation of newly synthesized macrophage markers. 28336715 10 85 from transition 1705:1714 arg1 secretion 1773:1781 secretion 1773:1781 secretion of proteins 1773:1793 Time-dependent changes observed in membrane protein presentation reflect functional remodeling during the phenotypic transition in three distinct phases: rapid surface presentation and secretion of proteins from intracellular pools concurrent with rapid internalization of no longer needed proteins and finally delayed presentation of newly synthesized macrophage markers. 28336715 10 85 from transition 1705:1714 arg1 presentation 1756:1767 rapid surface presentation 1742:1767 rapid surface presentation 1742:1767 Time-dependent changes observed in membrane protein presentation reflect functional remodeling during the phenotypic transition in three distinct phases: rapid surface presentation and secretion of proteins from intracellular pools concurrent with rapid internalization of no longer needed proteins and finally delayed presentation of newly synthesized macrophage markers. 28336715 4 86 theme glycoprotein-tagging 511:530 arg1 strategy 532:539 a chemical glycoprotein-tagging strategy 500:539 a chemical glycoprotein-tagging strategy with mass spectrometry 500:562 Here, we combined a chemical glycoprotein-tagging strategy with mass spectrometry to enable comprehensive analysis of the cell-surface glycoproteome. 28336715 11 87 theme macrophage 2083:2092 arg1 differentiation 2094:2108 macrophage differentiation 2083:2108 macrophage differentiation 2083:2108 Perturbation of this process using marketed receptor tyrosine kinase inhibitors revealed dasatinib to severely compromise macrophage differentiation due to an off-target activity. 28336715 5 88 theme standard 811:818 arg1 lines 842:846 15 standard laboratory human cell lines 808:846 15 standard laboratory human cell lines 808:846 To benchmark this workflow and to provide guidance for cell line selection for functional experiments, we generated an inventory of the N-linked cell-surface glycoproteomes of 15 standard laboratory human cell lines and three primary lymphocytic cell types. 28336715 9 89 theme time-resolved 1421:1433 arg1 analysis 1435:1442 the time-resolved analysis 1417:1442 the time-resolved analysis of plasma membrane protein presentation 1417:1482 This enabled the time-resolved analysis of plasma membrane protein presentation during differentiation of the monocytic suspension cell line THP-1 into macrophage-like adherent cells. 28336715 3 90 theme subproteome 366:376 arg1 abundance 348:356 The relatively low abundance 329:356 The relatively low abundance of this subproteome in conjunction with challenging extractability and solubility 329:438 The relatively low abundance of this subproteome in conjunction with challenging extractability and solubility still hampers its comprehensive analysis. 28336715 10 91 theme membrane 1623:1630 arg1 presentation 1640:1651 membrane protein presentation 1623:1651 membrane protein presentation 1623:1651 Time-dependent changes observed in membrane protein presentation reflect functional remodeling during the phenotypic transition in three distinct phases: rapid surface presentation and secretion of proteins from intracellular pools concurrent with rapid internalization of no longer needed proteins and finally delayed presentation of newly synthesized macrophage markers. 28336715 5 92 theme types 883:887 arg1 glycoproteomes 790:803 the N-linked cell-surface glycoproteomes 764:803 the N-linked cell-surface glycoproteomes of 15 standard laboratory human cell lines and three primary lymphocytic cell types 764:887 To benchmark this workflow and to provide guidance for cell line selection for functional experiments, we generated an inventory of the N-linked cell-surface glycoproteomes of 15 standard laboratory human cell lines and three primary lymphocytic cell types. 28336715 11 93 theme off-target 2120:2129 arg1 activity 2131:2138 an off-target activity 2117:2138 an off-target activity 2117:2138 Perturbation of this process using marketed receptor tyrosine kinase inhibitors revealed dasatinib to severely compromise macrophage differentiation due to an off-target activity. 28336715 4 94 theme glycoproteome 617:629 arg1 analysis 588:595 comprehensive analysis 574:595 comprehensive analysis of the cell-surface glycoproteome 574:629 Here, we combined a chemical glycoprotein-tagging strategy with mass spectrometry to enable comprehensive analysis of the cell-surface glycoproteome. 28336715 9 95 theme membrane 1454:1461 arg1 presentation 1471:1482 plasma membrane protein presentation 1447:1482 plasma membrane protein presentation 1447:1482 This enabled the time-resolved analysis of plasma membrane protein presentation during differentiation of the monocytic suspension cell line THP-1 into macrophage-like adherent cells. 28336715 10 96 theme functional 1661:1670 arg1 remodeling 1672:1681 functional remodeling 1661:1681 functional remodeling 1661:1681 Time-dependent changes observed in membrane protein presentation reflect functional remodeling during the phenotypic transition in three distinct phases: rapid surface presentation and secretion of proteins from intracellular pools concurrent with rapid internalization of no longer needed proteins and finally delayed presentation of newly synthesized macrophage markers. 28336715 10 97 theme needed 1871:1876 arg1 proteins 1878:1885 no longer needed proteins 1861:1885 no longer needed proteins 1861:1885 Time-dependent changes observed in membrane protein presentation reflect functional remodeling during the phenotypic transition in three distinct phases: rapid surface presentation and secretion of proteins from intracellular pools concurrent with rapid internalization of no longer needed proteins and finally delayed presentation of newly synthesized macrophage markers. 28336715 0 98 theme Quantitative 52:63 arg1 Proteomics 65:74 Quantitative Proteomics 52:74 Quantitative Proteomics 52:74 Monitoring Cell-surface N-Glycoproteome Dynamics by Quantitative Proteomics Reveals Mechanistic Insights into Macrophage Differentiation. 28336715 9 99 theme presentation 1471:1482 arg1 analysis 1435:1442 the time-resolved analysis 1417:1442 the time-resolved analysis of plasma membrane protein presentation 1417:1482 This enabled the time-resolved analysis of plasma membrane protein presentation during differentiation of the monocytic suspension cell line THP-1 into macrophage-like adherent cells. 28336715 6 100 theme secreted 932:939 arg1 proteins 941:948 secreted proteins 932:948 secreted proteins 932:948 On average, about 900 plasma membrane and secreted proteins were identified per experiment, including more than 300 transporters and ion channels. 28336715 7 101 theme processes 1234:1242 arg1 study 1203:1207 the study 1199:1207 the study of cell surface-mediated processes 1199:1242 Primary cells displayed distinct expression of surface markers and transporters underpinning the importance of carefully validating model cell lines selected for the study of cell surface-mediated processes. 28336715 5 102 theme glycoproteomes 790:803 arg1 inventory 751:759 an inventory 748:759 an inventory of the N-linked cell-surface glycoproteomes of 15 standard laboratory human cell lines and three primary lymphocytic cell types 748:887 To benchmark this workflow and to provide guidance for cell line selection for functional experiments, we generated an inventory of the N-linked cell-surface glycoproteomes of 15 standard laboratory human cell lines and three primary lymphocytic cell types. 28336715 11 103 theme process 1982:1988 arg1 Perturbation 1961:1972 Perturbation 1961:1972 Perturbation of this process using marketed receptor tyrosine kinase inhibitors 1961:2039 Perturbation of this process using marketed receptor tyrosine kinase inhibitors revealed dasatinib to severely compromise macrophage differentiation due to an off-target activity. 28336715 10 104 theme phenotypic 1694:1703 arg1 transition 1705:1714 the phenotypic transition 1690:1714 the phenotypic transition in three distinct phases: rapid surface presentation and secretion of proteins from intracellular pools concurrent with rapid internalization of no longer needed proteins and finally delayed presentation of newly synthesized macrophage markers 1690:1958 Time-dependent changes observed in membrane protein presentation reflect functional remodeling during the phenotypic transition in three distinct phases: rapid surface presentation and secretion of proteins from intracellular pools concurrent with rapid internalization of no longer needed proteins and finally delayed presentation of newly synthesized macrophage markers. 28336715 10 105 theme delayed 1899:1905 arg1 presentation 1907:1918 finally delayed presentation 1891:1918 finally delayed presentation of newly synthesized macrophage markers 1891:1958 Time-dependent changes observed in membrane protein presentation reflect functional remodeling during the phenotypic transition in three distinct phases: rapid surface presentation and secretion of proteins from intracellular pools concurrent with rapid internalization of no longer needed proteins and finally delayed presentation of newly synthesized macrophage markers. 28336715 4 106 with strategy 532:539 arg1 spectrometry 551:562 mass spectrometry 546:562 mass spectrometry 546:562 Here, we combined a chemical glycoprotein-tagging strategy with mass spectrometry to enable comprehensive analysis of the cell-surface glycoproteome. 28336715 9 107 theme suspension 1524:1533 arg1 THP-1 1545:1549 the monocytic suspension cell line THP-1 1510:1549 the monocytic suspension cell line THP-1 1510:1549 This enabled the time-resolved analysis of plasma membrane protein presentation during differentiation of the monocytic suspension cell line THP-1 into macrophage-like adherent cells. 28336715 10 108 theme distinct 1725:1732 arg1 phases 1734:1739 three distinct phases 1719:1739 three distinct phases: rapid surface presentation and secretion of proteins 1719:1793 Time-dependent changes observed in membrane protein presentation reflect functional remodeling during the phenotypic transition in three distinct phases: rapid surface presentation and secretion of proteins from intracellular pools concurrent with rapid internalization of no longer needed proteins and finally delayed presentation of newly synthesized macrophage markers. 28336715 10 108 theme distinct 1725:1732 arg1 secretion 1773:1781 secretion 1773:1781 secretion of proteins 1773:1793 Time-dependent changes observed in membrane protein presentation reflect functional remodeling during the phenotypic transition in three distinct phases: rapid surface presentation and secretion of proteins from intracellular pools concurrent with rapid internalization of no longer needed proteins and finally delayed presentation of newly synthesized macrophage markers. 28336715 10 108 theme distinct 1725:1732 arg1 presentation 1756:1767 rapid surface presentation 1742:1767 rapid surface presentation 1742:1767 Time-dependent changes observed in membrane protein presentation reflect functional remodeling during the phenotypic transition in three distinct phases: rapid surface presentation and secretion of proteins from intracellular pools concurrent with rapid internalization of no longer needed proteins and finally delayed presentation of newly synthesized macrophage markers. 28336715 0 109 theme Cell-surface 11:22 arg1 Dynamics 40:47 Cell-surface N-Glycoproteome Dynamics 11:47 Cell-surface N-Glycoproteome Dynamics 11:47 Monitoring Cell-surface N-Glycoproteome Dynamics by Quantitative Proteomics Reveals Mechanistic Insights into Macrophage Differentiation. 28336715 9 110 theme line 1540:1543 arg1 THP-1 1545:1549 the monocytic suspension cell line THP-1 1510:1549 the monocytic suspension cell line THP-1 1510:1549 This enabled the time-resolved analysis of plasma membrane protein presentation during differentiation of the monocytic suspension cell line THP-1 into macrophage-like adherent cells. 27658775 10 0 theme potential 1289:1297 arg1 target 1311:1316 a potential therapeutic target 1287:1316 a potential therapeutic target 1287:1316 These data suggest overexpression of IGFBP3 promotes tumor metastasis in NPC, which makes it a potential therapeutic target. 27658775 1 1 gly glycosylated 178:189 arg1 protein-3 144:152 Insulin-like growth factor-binding protein-3 109:152 Insulin-like growth factor-binding protein-3 (IGFBP3) 109:161 Insulin-like growth factor-binding protein-3 (IGFBP3) is an N-linked glycosylated, phosphorylated protein, which has been reported to regulate cancer progression and metastasis. 27658775 1 1 gly glycosylated 178:189 arg1 protein 207:213 an N-linked glycosylated, phosphorylated protein 166:213 an N-linked glycosylated, phosphorylated protein 166:213 Insulin-like growth factor-binding protein-3 (IGFBP3) is an N-linked glycosylated, phosphorylated protein, which has been reported to regulate cancer progression and metastasis. 27658775 2 2 from role 300:303 arg1 metastasis 324:333 tumor metastasis 318:333 tumor metastasis 318:333 However, the role of IGFBP3 in tumor metastasis remains under debate. 27658775 1 3 theme cancer 252:257 arg1 progression 259:269 cancer progression 252:269 cancer progression 252:269 Insulin-like growth factor-binding protein-3 (IGFBP3) is an N-linked glycosylated, phosphorylated protein, which has been reported to regulate cancer progression and metastasis. 27658775 6 4 theme N 771:771 arg1 classification 773:786 N classification 771:786 N classification 771:786 We found that IGFBP3 was significantly elevated in NPC and its expression level was correlated with N classification, distant metastasis, and TNM clinical stage (all P < 0.05). 27658775 9 5 theme recombinant 1139:1149 arg1 IGFBP3 1151:1156 recombinant IGFBP3 1139:1156 recombinant IGFBP3 1139:1156 Besides, NPC cells stimulated with recombinant IGFBP3 accelerated migration and adhesion. 27658775 3 6 theme Nasopharyngeal 357:370 arg1 cancer 425:430 a highly metastatic head and neck cancer 391:430 a highly metastatic head and neck cancer 391:430 Nasopharyngeal carcinoma (NPC) is a highly metastatic head and neck cancer. 27658775 3 6 theme Nasopharyngeal 357:370 arg1 NPC 383:385 NPC 383:385 NPC 383:385 Nasopharyngeal carcinoma (NPC) is a highly metastatic head and neck cancer. 27658775 3 6 theme Nasopharyngeal 357:370 arg1 carcinoma 372:380 Nasopharyngeal carcinoma 357:380 Nasopharyngeal carcinoma (NPC) 357:386 Nasopharyngeal carcinoma (NPC) is a highly metastatic head and neck cancer. 27658775 6 7 theme expression 734:743 arg1 level 745:749 its expression level 730:749 its expression level 730:749 We found that IGFBP3 was significantly elevated in NPC and its expression level was correlated with N classification, distant metastasis, and TNM clinical stage (all P < 0.05). 27658775 6 8 theme TNM 813:815 arg1 stage 826:830 TNM clinical stage 813:830 TNM clinical stage (all P < 0.05) 813:845 We found that IGFBP3 was significantly elevated in NPC and its expression level was correlated with N classification, distant metastasis, and TNM clinical stage (all P < 0.05). 27658775 6 8 theme TNM 813:815 arg1 P < 0.05 837:844 all P < 0.05 833:844 all P < 0.05 833:844 We found that IGFBP3 was significantly elevated in NPC and its expression level was correlated with N classification, distant metastasis, and TNM clinical stage (all P < 0.05). 27658775 0 9 theme nasopharyngeal 83:96 arg1 carcinoma 98:106 nasopharyngeal carcinoma 83:106 nasopharyngeal carcinoma 83:106 Overexpression of IGFBP3 is associated with poor prognosis and tumor metastasis in nasopharyngeal carcinoma. 27658775 0 10 from prognosis 49:57 arg1 carcinoma 98:106 nasopharyngeal carcinoma 83:106 nasopharyngeal carcinoma 83:106 Overexpression of IGFBP3 is associated with poor prognosis and tumor metastasis in nasopharyngeal carcinoma. 27658775 4 11 from efficacy 481:488 arg1 patients 493:500 patients 493:500 patients with metastasis 493:516 And it fails to achieve the desired therapeutic efficacy in patients with metastasis, while the role of IGFBP3 in NPC is still unclear. 27658775 7 12 theme poorer 892:897 arg1 P < 0.05 914:921 P < 0.05 914:921 P < 0.05 914:921 Patients with high expression of IGFBP3 had poorer survival rate (P < 0.05). 27658775 7 12 theme poorer 892:897 arg1 rate 908:911 poorer survival rate 892:911 poorer survival rate (P < 0.05) 892:922 Patients with high expression of IGFBP3 had poorer survival rate (P < 0.05). 27658775 10 13 theme tumor 1247:1251 arg1 metastasis 1253:1262 tumor metastasis 1247:1262 tumor metastasis 1247:1262 These data suggest overexpression of IGFBP3 promotes tumor metastasis in NPC, which makes it a potential therapeutic target. 27658775 1 14 theme N-linked 169:176 arg1 protein-3 144:152 Insulin-like growth factor-binding protein-3 109:152 Insulin-like growth factor-binding protein-3 (IGFBP3) 109:161 Insulin-like growth factor-binding protein-3 (IGFBP3) is an N-linked glycosylated, phosphorylated protein, which has been reported to regulate cancer progression and metastasis. 27658775 1 14 theme N-linked 169:176 arg1 protein 207:213 an N-linked glycosylated, phosphorylated protein 166:213 an N-linked glycosylated, phosphorylated protein 166:213 Insulin-like growth factor-binding protein-3 (IGFBP3) is an N-linked glycosylated, phosphorylated protein, which has been reported to regulate cancer progression and metastasis. 27658775 4 15 theme therapeutic 469:479 arg1 efficacy 481:488 the desired therapeutic efficacy 457:488 the desired therapeutic efficacy in patients with metastasis 457:516 And it fails to achieve the desired therapeutic efficacy in patients with metastasis, while the role of IGFBP3 in NPC is still unclear. 27658775 8 16 theme IGFBP3 970:975 arg1 downregulation 952:965 downregulation 952:965 downregulation of IGFBP3 952:975 In addition, we found that downregulation of IGFBP3 inhibited cell migration and adhesion by Transwell migration assay, wounding healing assay, and cell adhesion assays in vitro. 27658775 9 17 theme NPC 1113:1115 arg1 cells 1117:1121 NPC cells 1113:1121 NPC cells stimulated with recombinant IGFBP3 1113:1156 Besides, NPC cells stimulated with recombinant IGFBP3 accelerated migration and adhesion. 27658775 1 18 theme glycosylated 178:189 arg1 protein-3 144:152 Insulin-like growth factor-binding protein-3 109:152 Insulin-like growth factor-binding protein-3 (IGFBP3) 109:161 Insulin-like growth factor-binding protein-3 (IGFBP3) is an N-linked glycosylated, phosphorylated protein, which has been reported to regulate cancer progression and metastasis. 27658775 1 18 theme glycosylated 178:189 arg1 protein 207:213 an N-linked glycosylated, phosphorylated protein 166:213 an N-linked glycosylated, phosphorylated protein 166:213 Insulin-like growth factor-binding protein-3 (IGFBP3) is an N-linked glycosylated, phosphorylated protein, which has been reported to regulate cancer progression and metastasis. 27658775 4 19 theme desired 461:467 arg1 efficacy 481:488 the desired therapeutic efficacy 457:488 the desired therapeutic efficacy in patients with metastasis 457:516 And it fails to achieve the desired therapeutic efficacy in patients with metastasis, while the role of IGFBP3 in NPC is still unclear. 27658775 1 20 link N-linked 169:176 arg1 protein-3 144:152 Insulin-like growth factor-binding protein-3 109:152 Insulin-like growth factor-binding protein-3 (IGFBP3) 109:161 Insulin-like growth factor-binding protein-3 (IGFBP3) is an N-linked glycosylated, phosphorylated protein, which has been reported to regulate cancer progression and metastasis. 27658775 1 20 link N-linked 169:176 arg1 protein 207:213 an N-linked glycosylated, phosphorylated protein 166:213 an N-linked glycosylated, phosphorylated protein 166:213 Insulin-like growth factor-binding protein-3 (IGFBP3) is an N-linked glycosylated, phosphorylated protein, which has been reported to regulate cancer progression and metastasis. 27658775 5 21 used used 593:596 arg2 we 584:585 we 584:585 we 584:585 In this study, we first used immunohistochemistry to explore the expression of IGFBP3 in NPC tissues. 27658775 8 22 theme cell 987:990 arg1 migration 992:1000 cell migration 987:1000 cell migration 987:1000 In addition, we found that downregulation of IGFBP3 inhibited cell migration and adhesion by Transwell migration assay, wounding healing assay, and cell adhesion assays in vitro. 27658775 7 23 theme high 862:865 arg1 expression 867:876 high expression 862:876 high expression of IGFBP3 862:886 Patients with high expression of IGFBP3 had poorer survival rate (P < 0.05). 27658775 2 24 theme IGFBP3 308:313 arg1 role 300:303 the role 296:303 the role of IGFBP3 in tumor metastasis 296:333 However, the role of IGFBP3 in tumor metastasis remains under debate. 27658775 3 25 theme neck 420:423 arg1 cancer 425:430 a highly metastatic head and neck cancer 391:430 a highly metastatic head and neck cancer 391:430 Nasopharyngeal carcinoma (NPC) is a highly metastatic head and neck cancer. 27658775 3 25 theme neck 420:423 arg1 carcinoma 372:380 Nasopharyngeal carcinoma 357:380 Nasopharyngeal carcinoma (NPC) 357:386 Nasopharyngeal carcinoma (NPC) is a highly metastatic head and neck cancer. 27658775 5 26 theme NPC 658:660 arg1 tissues 662:668 NPC tissues 658:668 NPC tissues 658:668 In this study, we first used immunohistochemistry to explore the expression of IGFBP3 in NPC tissues. 27658775 10 27 theme therapeutic 1299:1309 arg1 target 1311:1316 a potential therapeutic target 1287:1316 a potential therapeutic target 1287:1316 These data suggest overexpression of IGFBP3 promotes tumor metastasis in NPC, which makes it a potential therapeutic target. 27658775 7 28 theme survival 899:906 arg1 P < 0.05 914:921 P < 0.05 914:921 P < 0.05 914:921 Patients with high expression of IGFBP3 had poorer survival rate (P < 0.05). 27658775 7 28 theme survival 899:906 arg1 rate 908:911 poorer survival rate 892:911 poorer survival rate (P < 0.05) 892:922 Patients with high expression of IGFBP3 had poorer survival rate (P < 0.05). 27658775 0 29 theme IGFBP3 18:23 arg1 Overexpression 0:13 Overexpression 0:13 Overexpression of IGFBP3 0:23 Overexpression of IGFBP3 is associated with poor prognosis and tumor metastasis in nasopharyngeal carcinoma. 27658775 6 30 theme clinical 817:824 arg1 stage 826:830 TNM clinical stage 813:830 TNM clinical stage (all P < 0.05) 813:845 We found that IGFBP3 was significantly elevated in NPC and its expression level was correlated with N classification, distant metastasis, and TNM clinical stage (all P < 0.05). 27658775 6 30 theme clinical 817:824 arg1 P < 0.05 837:844 all P < 0.05 833:844 all P < 0.05 833:844 We found that IGFBP3 was significantly elevated in NPC and its expression level was correlated with N classification, distant metastasis, and TNM clinical stage (all P < 0.05). 27658775 1 31 theme Insulin-like 109:120 arg1 protein-3 144:152 Insulin-like growth factor-binding protein-3 109:152 Insulin-like growth factor-binding protein-3 (IGFBP3) 109:161 Insulin-like growth factor-binding protein-3 (IGFBP3) is an N-linked glycosylated, phosphorylated protein, which has been reported to regulate cancer progression and metastasis. 27658775 1 31 theme Insulin-like 109:120 arg1 protein 207:213 an N-linked glycosylated, phosphorylated protein 166:213 an N-linked glycosylated, phosphorylated protein 166:213 Insulin-like growth factor-binding protein-3 (IGFBP3) is an N-linked glycosylated, phosphorylated protein, which has been reported to regulate cancer progression and metastasis. 27658775 1 31 theme Insulin-like 109:120 arg1 IGFBP3 155:160 IGFBP3 155:160 IGFBP3 155:160 Insulin-like growth factor-binding protein-3 (IGFBP3) is an N-linked glycosylated, phosphorylated protein, which has been reported to regulate cancer progression and metastasis. 27658775 3 32 theme metastatic 400:409 arg1 cancer 425:430 a highly metastatic head and neck cancer 391:430 a highly metastatic head and neck cancer 391:430 Nasopharyngeal carcinoma (NPC) is a highly metastatic head and neck cancer. 27658775 3 32 theme metastatic 400:409 arg1 carcinoma 372:380 Nasopharyngeal carcinoma 357:380 Nasopharyngeal carcinoma (NPC) 357:386 Nasopharyngeal carcinoma (NPC) is a highly metastatic head and neck cancer. 27658775 4 33 theme IGFBP3 537:542 arg1 unclear 560:566 unclear 560:566 unclear 560:566 And it fails to achieve the desired therapeutic efficacy in patients with metastasis, while the role of IGFBP3 in NPC is still unclear. 27658775 4 33 theme IGFBP3 537:542 arg1 role 529:532 the role 525:532 the role of IGFBP3 in NPC 525:549 And it fails to achieve the desired therapeutic efficacy in patients with metastasis, while the role of IGFBP3 in NPC is still unclear. 27658775 8 34 theme Transwell 1018:1026 arg1 assay 1038:1042 Transwell migration assay 1018:1042 Transwell migration assay 1018:1042 In addition, we found that downregulation of IGFBP3 inhibited cell migration and adhesion by Transwell migration assay, wounding healing assay, and cell adhesion assays in vitro. 27658775 0 35 from metastasis 69:78 arg1 carcinoma 98:106 nasopharyngeal carcinoma 83:106 nasopharyngeal carcinoma 83:106 Overexpression of IGFBP3 is associated with poor prognosis and tumor metastasis in nasopharyngeal carcinoma. 27658775 10 36 theme IGFBP3 1231:1236 arg1 overexpression 1213:1226 overexpression 1213:1226 overexpression of IGFBP3 1213:1236 These data suggest overexpression of IGFBP3 promotes tumor metastasis in NPC, which makes it a potential therapeutic target. 27658775 3 37 theme head 411:414 arg1 cancer 425:430 a highly metastatic head and neck cancer 391:430 a highly metastatic head and neck cancer 391:430 Nasopharyngeal carcinoma (NPC) is a highly metastatic head and neck cancer. 27658775 3 37 theme head 411:414 arg1 carcinoma 372:380 Nasopharyngeal carcinoma 357:380 Nasopharyngeal carcinoma (NPC) 357:386 Nasopharyngeal carcinoma (NPC) is a highly metastatic head and neck cancer. 27658775 7 38 contain had 888:890 arg2 rate 908:911 poorer survival rate 892:911 poorer survival rate (P < 0.05) 892:922 Patients with high expression of IGFBP3 had poorer survival rate (P < 0.05). 27658775 7 38 contain had 888:890 arg1 Patients 848:855 Patients 848:855 Patients with high expression of IGFBP3 848:886 Patients with high expression of IGFBP3 had poorer survival rate (P < 0.05). 27658775 7 38 contain had 888:890 arg2 P < 0.05 914:921 P < 0.05 914:921 P < 0.05 914:921 Patients with high expression of IGFBP3 had poorer survival rate (P < 0.05). 27658775 4 39 with patients 493:500 arg1 metastasis 507:516 metastasis 507:516 metastasis 507:516 And it fails to achieve the desired therapeutic efficacy in patients with metastasis, while the role of IGFBP3 in NPC is still unclear. 27658775 8 40 theme adhesion 1078:1085 arg1 assays 1087:1092 cell adhesion assays 1073:1092 cell adhesion assays 1073:1092 In addition, we found that downregulation of IGFBP3 inhibited cell migration and adhesion by Transwell migration assay, wounding healing assay, and cell adhesion assays in vitro. 27658775 8 41 theme healing 1054:1060 arg1 assay 1062:1066 wounding healing assay 1045:1066 wounding healing assay 1045:1066 In addition, we found that downregulation of IGFBP3 inhibited cell migration and adhesion by Transwell migration assay, wounding healing assay, and cell adhesion assays in vitro. 27658775 7 42 with Patients 848:855 arg1 expression 867:876 high expression 862:876 high expression of IGFBP3 862:886 Patients with high expression of IGFBP3 had poorer survival rate (P < 0.05). 27658775 1 43 theme growth 122:127 arg1 protein-3 144:152 Insulin-like growth factor-binding protein-3 109:152 Insulin-like growth factor-binding protein-3 (IGFBP3) 109:161 Insulin-like growth factor-binding protein-3 (IGFBP3) is an N-linked glycosylated, phosphorylated protein, which has been reported to regulate cancer progression and metastasis. 27658775 1 43 theme growth 122:127 arg1 protein 207:213 an N-linked glycosylated, phosphorylated protein 166:213 an N-linked glycosylated, phosphorylated protein 166:213 Insulin-like growth factor-binding protein-3 (IGFBP3) is an N-linked glycosylated, phosphorylated protein, which has been reported to regulate cancer progression and metastasis. 27658775 1 43 theme growth 122:127 arg1 IGFBP3 155:160 IGFBP3 155:160 IGFBP3 155:160 Insulin-like growth factor-binding protein-3 (IGFBP3) is an N-linked glycosylated, phosphorylated protein, which has been reported to regulate cancer progression and metastasis. 27658775 0 44 theme poor 44:47 arg1 prognosis 49:57 poor prognosis 44:57 poor prognosis 44:57 Overexpression of IGFBP3 is associated with poor prognosis and tumor metastasis in nasopharyngeal carcinoma. 27658775 8 45 theme migration 1028:1036 arg1 assay 1038:1042 Transwell migration assay 1018:1042 Transwell migration assay 1018:1042 In addition, we found that downregulation of IGFBP3 inhibited cell migration and adhesion by Transwell migration assay, wounding healing assay, and cell adhesion assays in vitro. 27658775 1 46 dep glycosylated 178:189 arg1 phosphorylated 192:205 phosphorylated 192:205 phosphorylated 192:205 Insulin-like growth factor-binding protein-3 (IGFBP3) is an N-linked glycosylated, phosphorylated protein, which has been reported to regulate cancer progression and metastasis. 27658775 1 47 theme factor-binding 129:142 arg1 protein-3 144:152 Insulin-like growth factor-binding protein-3 109:152 Insulin-like growth factor-binding protein-3 (IGFBP3) 109:161 Insulin-like growth factor-binding protein-3 (IGFBP3) is an N-linked glycosylated, phosphorylated protein, which has been reported to regulate cancer progression and metastasis. 27658775 1 47 theme factor-binding 129:142 arg1 protein 207:213 an N-linked glycosylated, phosphorylated protein 166:213 an N-linked glycosylated, phosphorylated protein 166:213 Insulin-like growth factor-binding protein-3 (IGFBP3) is an N-linked glycosylated, phosphorylated protein, which has been reported to regulate cancer progression and metastasis. 27658775 1 47 theme factor-binding 129:142 arg1 IGFBP3 155:160 IGFBP3 155:160 IGFBP3 155:160 Insulin-like growth factor-binding protein-3 (IGFBP3) is an N-linked glycosylated, phosphorylated protein, which has been reported to regulate cancer progression and metastasis. 27658775 5 48 theme IGFBP3 648:653 arg1 expression 634:643 the expression 630:643 the expression of IGFBP3 in NPC tissues 630:668 In this study, we first used immunohistochemistry to explore the expression of IGFBP3 in NPC tissues. 27658775 6 49 theme distant 789:795 arg1 metastasis 797:806 distant metastasis 789:806 distant metastasis 789:806 We found that IGFBP3 was significantly elevated in NPC and its expression level was correlated with N classification, distant metastasis, and TNM clinical stage (all P < 0.05). 27658775 8 50 theme wounding 1045:1052 arg1 assay 1062:1066 wounding healing assay 1045:1066 wounding healing assay 1045:1066 In addition, we found that downregulation of IGFBP3 inhibited cell migration and adhesion by Transwell migration assay, wounding healing assay, and cell adhesion assays in vitro. 27658775 2 51 theme tumor 318:322 arg1 metastasis 324:333 tumor metastasis 318:333 tumor metastasis 318:333 However, the role of IGFBP3 in tumor metastasis remains under debate. 27658775 0 52 theme tumor 63:67 arg1 metastasis 69:78 tumor metastasis 63:78 tumor metastasis 63:78 Overexpression of IGFBP3 is associated with poor prognosis and tumor metastasis in nasopharyngeal carcinoma. 27658775 5 53 from expression 634:643 arg1 tissues 662:668 NPC tissues 658:668 NPC tissues 658:668 In this study, we first used immunohistochemistry to explore the expression of IGFBP3 in NPC tissues. 27658775 7 54 theme IGFBP3 881:886 arg1 expression 867:876 high expression 862:876 high expression of IGFBP3 862:886 Patients with high expression of IGFBP3 had poorer survival rate (P < 0.05). 27658775 4 55 from role 529:532 arg1 NPC 547:549 NPC 547:549 NPC 547:549 And it fails to achieve the desired therapeutic efficacy in patients with metastasis, while the role of IGFBP3 in NPC is still unclear. 27658775 8 56 theme cell 1073:1076 arg1 assays 1087:1092 cell adhesion assays 1073:1092 cell adhesion assays 1073:1092 In addition, we found that downregulation of IGFBP3 inhibited cell migration and adhesion by Transwell migration assay, wounding healing assay, and cell adhesion assays in vitro. 27487926 2 0 gly glycoproteins 280:292 arg1 glycoproteins 280:292 the N-linked glycoproteins 267:292 the N-linked glycoproteins 267:292 The F-box protein Fbs1, which recognizes the N-linked glycoproteins, is involved in the endoplasmic reticulum-associated degradation pathway. 27487926 4 1 theme crystal 568:574 arg1 structure 576:584 the crystal structure 564:584 the crystal structure of a mutant substrate-binding domain of Fbs1 in which the six nonconserved regions (β1, β2-β3, β3-β4, β5-β6, β7-β8 and β9-β10) of Fbs1 were substituted with those of FBG3 564:755 To investigate the sequence-structure relationship of the substrate-binding pocket, the crystal structure of a mutant substrate-binding domain of Fbs1 in which the six nonconserved regions (β1, β2-β3, β3-β4, β5-β6, β7-β8 and β9-β10) of Fbs1 were substituted with those of FBG3 was determined. 27487926 0 2 theme domain 86:91 arg1 mutant 50:55 a function-associated loop mutant 23:55 a function-associated loop mutant of the substrate-recognition domain of Fbs1 ubiquitin ligase 23:116 Structural analysis of a function-associated loop mutant of the substrate-recognition domain of Fbs1 ubiquitin ligase. 27487926 4 3 theme sequence-structure 499:516 arg1 relationship 518:529 the sequence-structure relationship 495:529 the sequence-structure relationship of the substrate-binding pocket 495:561 To investigate the sequence-structure relationship of the substrate-binding pocket, the crystal structure of a mutant substrate-binding domain of Fbs1 in which the six nonconserved regions (β1, β2-β3, β3-β4, β5-β6, β7-β8 and β9-β10) of Fbs1 were substituted with those of FBG3 was determined. 27487926 2 4 theme degradation 347:357 arg1 pathway 359:365 the endoplasmic reticulum-associated degradation pathway 310:365 the endoplasmic reticulum-associated degradation pathway 310:365 The F-box protein Fbs1, which recognizes the N-linked glycoproteins, is involved in the endoplasmic reticulum-associated degradation pathway. 27487926 0 5 theme ubiquitin 101:109 arg1 ligase 111:116 Fbs1 ubiquitin ligase 96:116 Fbs1 ubiquitin ligase 96:116 Structural analysis of a function-associated loop mutant of the substrate-recognition domain of Fbs1 ubiquitin ligase. 27487926 2 6 theme N-linked 271:278 arg1 glycoproteins 280:292 the N-linked glycoproteins 267:292 the N-linked glycoproteins 267:292 The F-box protein Fbs1, which recognizes the N-linked glycoproteins, is involved in the endoplasmic reticulum-associated degradation pathway. 27487926 4 7 theme mutant 591:596 arg1 domain 616:621 a mutant substrate-binding domain 589:621 a mutant substrate-binding domain of Fbs1 in which the six nonconserved regions (β1, β2-β3, β3-β4, β5-β6, β7-β8 and β9-β10) of Fbs1 were substituted with those of FBG3 589:755 To investigate the sequence-structure relationship of the substrate-binding pocket, the crystal structure of a mutant substrate-binding domain of Fbs1 in which the six nonconserved regions (β1, β2-β3, β3-β4, β5-β6, β7-β8 and β9-β10) of Fbs1 were substituted with those of FBG3 was determined. 27487926 4 7 theme mutant 591:596 arg1 Fbs1 626:629 Fbs1 626:629 Fbs1 in which the six nonconserved regions (β1, β2-β3, β3-β4, β5-β6, β7-β8 and β9-β10) of Fbs1 were substituted with those of FBG3 626:755 To investigate the sequence-structure relationship of the substrate-binding pocket, the crystal structure of a mutant substrate-binding domain of Fbs1 in which the six nonconserved regions (β1, β2-β3, β3-β4, β5-β6, β7-β8 and β9-β10) of Fbs1 were substituted with those of FBG3 was determined. 27487926 0 8 theme Fbs1 96:99 arg1 ligase 111:116 Fbs1 ubiquitin ligase 96:116 Fbs1 ubiquitin ligase 96:116 Structural analysis of a function-associated loop mutant of the substrate-recognition domain of Fbs1 ubiquitin ligase. 27487926 4 9 theme Fbs1 716:719 arg1 regions 661:667 the six nonconserved regions 640:667 the six nonconserved regions (β1, β2-β3, β3-β4, β5-β6, β7-β8 and β9-β10) of Fbs1 640:719 To investigate the sequence-structure relationship of the substrate-binding pocket, the crystal structure of a mutant substrate-binding domain of Fbs1 in which the six nonconserved regions (β1, β2-β3, β3-β4, β5-β6, β7-β8 and β9-β10) of Fbs1 were substituted with those of FBG3 was determined. 27487926 0 10 theme ligase 111:116 arg1 domain 86:91 the substrate-recognition domain 60:91 the substrate-recognition domain of Fbs1 ubiquitin ligase 60:116 Structural analysis of a function-associated loop mutant of the substrate-recognition domain of Fbs1 ubiquitin ligase. 27487926 0 10 theme ligase 111:116 arg1 ligase 111:116 Fbs1 ubiquitin ligase 96:116 Fbs1 ubiquitin ligase 96:116 Structural analysis of a function-associated loop mutant of the substrate-recognition domain of Fbs1 ubiquitin ligase. 27487926 3 11 theme F-box 391:395 arg1 FBG3 377:380 FBG3 377:380 FBG3 377:380 Although FBG3, another F-box protein, shares 51% sequence identity with Fbs1, FBG3 does not bind glycoproteins. 27487926 3 11 theme F-box 391:395 arg1 protein 397:403 another F-box protein 383:403 another F-box protein 383:403 Although FBG3, another F-box protein, shares 51% sequence identity with Fbs1, FBG3 does not bind glycoproteins. 27487926 4 12 theme nonconserved 648:659 arg1 regions 661:667 the six nonconserved regions 640:667 the six nonconserved regions (β1, β2-β3, β3-β4, β5-β6, β7-β8 and β9-β10) of Fbs1 640:719 To investigate the sequence-structure relationship of the substrate-binding pocket, the crystal structure of a mutant substrate-binding domain of Fbs1 in which the six nonconserved regions (β1, β2-β3, β3-β4, β5-β6, β7-β8 and β9-β10) of Fbs1 were substituted with those of FBG3 was determined. 27487926 1 13 dep components 159:168 arg1 Cul1 177:180 Cul1 177:180 Cul1 177:180 The SCF ubiquitin ligase comprises four components: Skp1, Cul1, Rbx1 and a variable-subunit F-box protein. 27487926 1 13 dep components 159:168 arg1 Skp1 171:174 Skp1 171:174 Skp1 171:174 The SCF ubiquitin ligase comprises four components: Skp1, Cul1, Rbx1 and a variable-subunit F-box protein. 27487926 1 13 dep components 159:168 arg1 components 159:168 four components 154:168 four components: Skp1, Cul1, Rbx1 and a variable-subunit F-box protein 154:223 The SCF ubiquitin ligase comprises four components: Skp1, Cul1, Rbx1 and a variable-subunit F-box protein. 27487926 1 13 dep components 159:168 arg1 protein 217:223 a variable-subunit F-box protein 192:223 a variable-subunit F-box protein 192:223 The SCF ubiquitin ligase comprises four components: Skp1, Cul1, Rbx1 and a variable-subunit F-box protein. 27487926 1 13 dep components 159:168 arg1 Rbx1 183:186 Rbx1 183:186 Rbx1 183:186 The SCF ubiquitin ligase comprises four components: Skp1, Cul1, Rbx1 and a variable-subunit F-box protein. 27487926 3 14 theme % 415:415 arg1 identity 426:433 51% sequence identity 413:433 51% sequence identity 413:433 Although FBG3, another F-box protein, shares 51% sequence identity with Fbs1, FBG3 does not bind glycoproteins. 27487926 0 15 theme Structural 0:9 arg1 analysis 11:18 Structural analysis 0:18 Structural analysis of a function-associated loop mutant of the substrate-recognition domain of Fbs1 ubiquitin ligase. 0:117 Structural analysis of a function-associated loop mutant of the substrate-recognition domain of Fbs1 ubiquitin ligase. 27487926 3 16 gly glycoproteins 465:477 arg1 glycoproteins 465:477 glycoproteins 465:477 glycoproteins 465:477 Although FBG3, another F-box protein, shares 51% sequence identity with Fbs1, FBG3 does not bind glycoproteins. 27487926 3 17 theme sequence 417:424 arg1 identity 426:433 51% sequence identity 413:433 51% sequence identity 413:433 Although FBG3, another F-box protein, shares 51% sequence identity with Fbs1, FBG3 does not bind glycoproteins. 27487926 4 18 theme pocket 556:561 arg1 relationship 518:529 the sequence-structure relationship 495:529 the sequence-structure relationship of the substrate-binding pocket 495:561 To investigate the sequence-structure relationship of the substrate-binding pocket, the crystal structure of a mutant substrate-binding domain of Fbs1 in which the six nonconserved regions (β1, β2-β3, β3-β4, β5-β6, β7-β8 and β9-β10) of Fbs1 were substituted with those of FBG3 was determined. 27487926 5 19 theme substrate-binding 777:793 arg1 pocket 795:800 The substrate-binding pocket 773:800 The substrate-binding pocket of this model 773:814 The substrate-binding pocket of this model exhibits structural features that differ from those of Fsb1. 27487926 2 20 link N-linked 271:278 arg1 glycoproteins 280:292 the N-linked glycoproteins 267:292 the N-linked glycoproteins 267:292 The F-box protein Fbs1, which recognizes the N-linked glycoproteins, is involved in the endoplasmic reticulum-associated degradation pathway. 27487926 0 21 theme loop 45:48 arg1 mutant 50:55 a function-associated loop mutant 23:55 a function-associated loop mutant of the substrate-recognition domain of Fbs1 ubiquitin ligase 23:116 Structural analysis of a function-associated loop mutant of the substrate-recognition domain of Fbs1 ubiquitin ligase. 27487926 2 22 theme endoplasmic 314:324 arg1 pathway 359:365 the endoplasmic reticulum-associated degradation pathway 310:365 the endoplasmic reticulum-associated degradation pathway 310:365 The F-box protein Fbs1, which recognizes the N-linked glycoproteins, is involved in the endoplasmic reticulum-associated degradation pathway. 27487926 0 23 theme function-associated 25:43 arg1 mutant 50:55 a function-associated loop mutant 23:55 a function-associated loop mutant of the substrate-recognition domain of Fbs1 ubiquitin ligase 23:116 Structural analysis of a function-associated loop mutant of the substrate-recognition domain of Fbs1 ubiquitin ligase. 27487926 3 24 theme 51 413:414 arg1 % 415:415 % 415:415 % 415:415 Although FBG3, another F-box protein, shares 51% sequence identity with Fbs1, FBG3 does not bind glycoproteins. 27487926 1 25 theme variable-subunit 194:209 arg1 components 159:168 four components 154:168 four components: Skp1, Cul1, Rbx1 and a variable-subunit F-box protein 154:223 The SCF ubiquitin ligase comprises four components: Skp1, Cul1, Rbx1 and a variable-subunit F-box protein. 27487926 1 25 theme variable-subunit 194:209 arg1 protein 217:223 a variable-subunit F-box protein 192:223 a variable-subunit F-box protein 192:223 The SCF ubiquitin ligase comprises four components: Skp1, Cul1, Rbx1 and a variable-subunit F-box protein. 27487926 2 26 theme reticulum-associated 326:345 arg1 pathway 359:365 the endoplasmic reticulum-associated degradation pathway 310:365 the endoplasmic reticulum-associated degradation pathway 310:365 The F-box protein Fbs1, which recognizes the N-linked glycoproteins, is involved in the endoplasmic reticulum-associated degradation pathway. 27487926 0 27 theme mutant 50:55 arg1 analysis 11:18 Structural analysis 0:18 Structural analysis of a function-associated loop mutant of the substrate-recognition domain of Fbs1 ubiquitin ligase. 0:117 Structural analysis of a function-associated loop mutant of the substrate-recognition domain of Fbs1 ubiquitin ligase. 27487926 4 28 theme substrate-binding 538:554 arg1 pocket 556:561 the substrate-binding pocket 534:561 the substrate-binding pocket 534:561 To investigate the sequence-structure relationship of the substrate-binding pocket, the crystal structure of a mutant substrate-binding domain of Fbs1 in which the six nonconserved regions (β1, β2-β3, β3-β4, β5-β6, β7-β8 and β9-β10) of Fbs1 were substituted with those of FBG3 was determined. 27487926 1 29 theme SCF 123:125 arg1 ligase 137:142 The SCF ubiquitin ligase 119:142 The SCF ubiquitin ligase 119:142 The SCF ubiquitin ligase comprises four components: Skp1, Cul1, Rbx1 and a variable-subunit F-box protein. 27487926 1 30 theme ubiquitin 127:135 arg1 ligase 137:142 The SCF ubiquitin ligase 119:142 The SCF ubiquitin ligase 119:142 The SCF ubiquitin ligase comprises four components: Skp1, Cul1, Rbx1 and a variable-subunit F-box protein. 27487926 1 31 theme F-box 211:215 arg1 components 159:168 four components 154:168 four components: Skp1, Cul1, Rbx1 and a variable-subunit F-box protein 154:223 The SCF ubiquitin ligase comprises four components: Skp1, Cul1, Rbx1 and a variable-subunit F-box protein. 27487926 1 31 theme F-box 211:215 arg1 protein 217:223 a variable-subunit F-box protein 192:223 a variable-subunit F-box protein 192:223 The SCF ubiquitin ligase comprises four components: Skp1, Cul1, Rbx1 and a variable-subunit F-box protein. 27487926 4 32 dep regions 661:667 arg1 β9-β10 705:710 β9-β10 705:710 β9-β10 705:710 To investigate the sequence-structure relationship of the substrate-binding pocket, the crystal structure of a mutant substrate-binding domain of Fbs1 in which the six nonconserved regions (β1, β2-β3, β3-β4, β5-β6, β7-β8 and β9-β10) of Fbs1 were substituted with those of FBG3 was determined. 27487926 4 32 dep regions 661:667 arg1 β7-β8 695:699 β7-β8 695:699 β7-β8 695:699 To investigate the sequence-structure relationship of the substrate-binding pocket, the crystal structure of a mutant substrate-binding domain of Fbs1 in which the six nonconserved regions (β1, β2-β3, β3-β4, β5-β6, β7-β8 and β9-β10) of Fbs1 were substituted with those of FBG3 was determined. 27487926 4 33 theme substrate-binding 598:614 arg1 domain 616:621 a mutant substrate-binding domain 589:621 a mutant substrate-binding domain of Fbs1 in which the six nonconserved regions (β1, β2-β3, β3-β4, β5-β6, β7-β8 and β9-β10) of Fbs1 were substituted with those of FBG3 589:755 To investigate the sequence-structure relationship of the substrate-binding pocket, the crystal structure of a mutant substrate-binding domain of Fbs1 in which the six nonconserved regions (β1, β2-β3, β3-β4, β5-β6, β7-β8 and β9-β10) of Fbs1 were substituted with those of FBG3 was determined. 27487926 4 33 theme substrate-binding 598:614 arg1 Fbs1 626:629 Fbs1 626:629 Fbs1 in which the six nonconserved regions (β1, β2-β3, β3-β4, β5-β6, β7-β8 and β9-β10) of Fbs1 were substituted with those of FBG3 626:755 To investigate the sequence-structure relationship of the substrate-binding pocket, the crystal structure of a mutant substrate-binding domain of Fbs1 in which the six nonconserved regions (β1, β2-β3, β3-β4, β5-β6, β7-β8 and β9-β10) of Fbs1 were substituted with those of FBG3 was determined. 27487926 0 34 theme substrate-recognition 64:84 arg1 domain 86:91 the substrate-recognition domain 60:91 the substrate-recognition domain of Fbs1 ubiquitin ligase 60:116 Structural analysis of a function-associated loop mutant of the substrate-recognition domain of Fbs1 ubiquitin ligase. 27487926 0 34 theme substrate-recognition 64:84 arg1 ligase 111:116 Fbs1 ubiquitin ligase 96:116 Fbs1 ubiquitin ligase 96:116 Structural analysis of a function-associated loop mutant of the substrate-recognition domain of Fbs1 ubiquitin ligase. 27487926 5 35 theme model 810:814 arg1 pocket 795:800 The substrate-binding pocket 773:800 The substrate-binding pocket of this model 773:814 The substrate-binding pocket of this model exhibits structural features that differ from those of Fsb1. 27487926 2 36 theme protein 236:242 arg1 Fbs1 244:247 The F-box protein Fbs1 226:247 The F-box protein Fbs1 226:247 The F-box protein Fbs1, which recognizes the N-linked glycoproteins, is involved in the endoplasmic reticulum-associated degradation pathway. 27487926 5 37 theme structural 825:834 arg1 features 836:843 structural features 825:843 structural features that differ from those of Fsb1 825:874 The substrate-binding pocket of this model exhibits structural features that differ from those of Fsb1. 27487926 4 38 theme Fbs1 626:629 arg1 domain 616:621 a mutant substrate-binding domain 589:621 a mutant substrate-binding domain of Fbs1 in which the six nonconserved regions (β1, β2-β3, β3-β4, β5-β6, β7-β8 and β9-β10) of Fbs1 were substituted with those of FBG3 589:755 To investigate the sequence-structure relationship of the substrate-binding pocket, the crystal structure of a mutant substrate-binding domain of Fbs1 in which the six nonconserved regions (β1, β2-β3, β3-β4, β5-β6, β7-β8 and β9-β10) of Fbs1 were substituted with those of FBG3 was determined. 27487926 4 38 theme Fbs1 626:629 arg1 Fbs1 626:629 Fbs1 626:629 Fbs1 in which the six nonconserved regions (β1, β2-β3, β3-β4, β5-β6, β7-β8 and β9-β10) of Fbs1 were substituted with those of FBG3 626:755 To investigate the sequence-structure relationship of the substrate-binding pocket, the crystal structure of a mutant substrate-binding domain of Fbs1 in which the six nonconserved regions (β1, β2-β3, β3-β4, β5-β6, β7-β8 and β9-β10) of Fbs1 were substituted with those of FBG3 was determined. 27487926 2 39 theme F-box 230:234 arg1 Fbs1 244:247 The F-box protein Fbs1 226:247 The F-box protein Fbs1 226:247 The F-box protein Fbs1, which recognizes the N-linked glycoproteins, is involved in the endoplasmic reticulum-associated degradation pathway. 27487926 4 40 theme domain 616:621 arg1 structure 576:584 the crystal structure 564:584 the crystal structure of a mutant substrate-binding domain of Fbs1 in which the six nonconserved regions (β1, β2-β3, β3-β4, β5-β6, β7-β8 and β9-β10) of Fbs1 were substituted with those of FBG3 564:755 To investigate the sequence-structure relationship of the substrate-binding pocket, the crystal structure of a mutant substrate-binding domain of Fbs1 in which the six nonconserved regions (β1, β2-β3, β3-β4, β5-β6, β7-β8 and β9-β10) of Fbs1 were substituted with those of FBG3 was determined. 24567334 3 0 theme Dsg2-associated 270:284 arg1 proteins 286:293 Dsg2-associated proteins 270:293 Dsg2-associated proteins in intestinal epithelial cells 270:324 A proteomic screen for Dsg2-associated proteins in intestinal epithelial cells identified a lectin referred to as galectin-3 (Gal3). 24567334 7 1 theme desmosomal 893:902 arg1 cadherin 904:911 a desmosomal cadherin 891:911 a desmosomal cadherin 891:911 These results report a novel role of Gal3 in stabilizing a desmosomal cadherin and intercellular adhesion in intestinal epithelial cells. 24567334 7 2 theme epithelial 954:963 arg1 cells 965:969 intestinal epithelial cells 943:969 intestinal epithelial cells 943:969 These results report a novel role of Gal3 in stabilizing a desmosomal cadherin and intercellular adhesion in intestinal epithelial cells. 24567334 7 3 from adhesion 931:938 arg1 cells 965:969 intestinal epithelial cells 943:969 intestinal epithelial cells 943:969 These results report a novel role of Gal3 in stabilizing a desmosomal cadherin and intercellular adhesion in intestinal epithelial cells. 24567334 3 4 theme proteomic 249:257 arg1 screen 259:264 A proteomic screen 247:264 A proteomic screen for Dsg2-associated proteins in intestinal epithelial cells 247:324 A proteomic screen for Dsg2-associated proteins in intestinal epithelial cells identified a lectin referred to as galectin-3 (Gal3). 24567334 5 5 theme intestinal 683:692 arg1 cells 705:709 intestinal epithelial cells 683:709 intestinal epithelial cells 683:709 Down-regulation of Gal3 protein or incubation with lactose, a galactose-containing disaccharide that competitively inhibits galectin binding to Dsg2, decreased intercellular adhesion in intestinal epithelial cells. 24567334 2 6 theme intestinal 185:194 arg1 cells 207:211 Human intestinal epithelial cells 179:211 Human intestinal epithelial cells 179:211 Human intestinal epithelial cells express the desmoglein-2 isoform. 24567334 5 7 theme epithelial 694:703 arg1 cells 705:709 intestinal epithelial cells 683:709 intestinal epithelial cells 683:709 Down-regulation of Gal3 protein or incubation with lactose, a galactose-containing disaccharide that competitively inhibits galectin binding to Dsg2, decreased intercellular adhesion in intestinal epithelial cells. 24567334 4 8 link N-linked 394:401 arg1 β-galactosides 403:416 N-linked β-galactosides 394:416 N-linked β-galactosides in Dsg2 extracellular domain 394:445 Gal3 bound to N-linked β-galactosides in Dsg2 extracellular domain and co-sedimented with caveolin-1 in lipid rafts. 24567334 2 9 theme Human 179:183 arg1 cells 207:211 Human intestinal epithelial cells 179:211 Human intestinal epithelial cells 179:211 Human intestinal epithelial cells express the desmoglein-2 isoform. 24567334 3 10 theme intestinal 298:307 arg1 cells 320:324 intestinal epithelial cells 298:324 intestinal epithelial cells 298:324 A proteomic screen for Dsg2-associated proteins in intestinal epithelial cells identified a lectin referred to as galectin-3 (Gal3). 24567334 1 11 theme desmosomal 88:97 arg1 desmogleins 110:120 desmogleins 110:120 desmogleins 110:120 The desmosomal cadherins, desmogleins, and desmocollins mediate strong intercellular adhesion. 24567334 1 11 theme desmosomal 88:97 arg1 desmocollins 127:138 desmocollins 127:138 desmocollins 127:138 The desmosomal cadherins, desmogleins, and desmocollins mediate strong intercellular adhesion. 24567334 1 11 theme desmosomal 88:97 arg1 cadherins 99:107 The desmosomal cadherins 84:107 The desmosomal cadherins 84:107 The desmosomal cadherins, desmogleins, and desmocollins mediate strong intercellular adhesion. 24567334 6 12 theme plasma 786:791 arg1 membrane 793:800 the plasma membrane 782:800 the plasma membrane 782:800 In the absence of functional Gal3, Dsg2 protein was internalized from the plasma membrane and degraded in the proteasome. 24567334 3 13 theme epithelial 309:318 arg1 cells 320:324 intestinal epithelial cells 298:324 intestinal epithelial cells 298:324 A proteomic screen for Dsg2-associated proteins in intestinal epithelial cells identified a lectin referred to as galectin-3 (Gal3). 24567334 7 14 theme intercellular 917:929 arg1 adhesion 931:938 intercellular adhesion 917:938 intercellular adhesion 917:938 These results report a novel role of Gal3 in stabilizing a desmosomal cadherin and intercellular adhesion in intestinal epithelial cells. 24567334 5 15 with Down-regulation 497:511 arg1 disaccharide 580:591 a galactose-containing disaccharide 557:591 a galactose-containing disaccharide that competitively inhibits galectin binding to Dsg2 557:644 Down-regulation of Gal3 protein or incubation with lactose, a galactose-containing disaccharide that competitively inhibits galectin binding to Dsg2, decreased intercellular adhesion in intestinal epithelial cells. 24567334 5 15 with Down-regulation 497:511 arg1 lactose 548:554 lactose 548:554 lactose 548:554 Down-regulation of Gal3 protein or incubation with lactose, a galactose-containing disaccharide that competitively inhibits galectin binding to Dsg2, decreased intercellular adhesion in intestinal epithelial cells. 24567334 5 16 theme galactose-containing 559:578 arg1 disaccharide 580:591 a galactose-containing disaccharide 557:591 a galactose-containing disaccharide that competitively inhibits galectin binding to Dsg2 557:644 Down-regulation of Gal3 protein or incubation with lactose, a galactose-containing disaccharide that competitively inhibits galectin binding to Dsg2, decreased intercellular adhesion in intestinal epithelial cells. 24567334 5 16 theme galactose-containing 559:578 arg1 lactose 548:554 lactose 548:554 lactose 548:554 Down-regulation of Gal3 protein or incubation with lactose, a galactose-containing disaccharide that competitively inhibits galectin binding to Dsg2, decreased intercellular adhesion in intestinal epithelial cells. 24567334 3 17 from proteins 286:293 arg1 cells 320:324 intestinal epithelial cells 298:324 intestinal epithelial cells 298:324 A proteomic screen for Dsg2-associated proteins in intestinal epithelial cells identified a lectin referred to as galectin-3 (Gal3). 24567334 2 18 theme desmoglein-2 225:236 arg1 isoform 238:244 the desmoglein-2 isoform 221:244 the desmoglein-2 isoform 221:244 Human intestinal epithelial cells express the desmoglein-2 isoform. 24567334 4 19 theme extracellular 426:438 arg1 domain 440:445 Dsg2 extracellular domain 421:445 Dsg2 extracellular domain 421:445 Gal3 bound to N-linked β-galactosides in Dsg2 extracellular domain and co-sedimented with caveolin-1 in lipid rafts. 24567334 5 20 theme protein 521:527 arg1 incubation 532:541 incubation 532:541 incubation with lactose, a galactose-containing disaccharide that competitively inhibits galectin binding to Dsg2, 532:645 Down-regulation of Gal3 protein or incubation with lactose, a galactose-containing disaccharide that competitively inhibits galectin binding to Dsg2, decreased intercellular adhesion in intestinal epithelial cells. 24567334 5 20 theme protein 521:527 arg1 Down-regulation 497:511 Down-regulation 497:511 Down-regulation of Gal3 protein 497:527 Down-regulation of Gal3 protein or incubation with lactose, a galactose-containing disaccharide that competitively inhibits galectin binding to Dsg2, decreased intercellular adhesion in intestinal epithelial cells. 24567334 5 21 theme intercellular 657:669 arg1 adhesion 671:678 intercellular adhesion 657:678 intercellular adhesion 657:678 Down-regulation of Gal3 protein or incubation with lactose, a galactose-containing disaccharide that competitively inhibits galectin binding to Dsg2, decreased intercellular adhesion in intestinal epithelial cells. 24567334 4 22 theme Dsg2 421:424 arg1 domain 440:445 Dsg2 extracellular domain 421:445 Dsg2 extracellular domain 421:445 Gal3 bound to N-linked β-galactosides in Dsg2 extracellular domain and co-sedimented with caveolin-1 in lipid rafts. 24567334 0 23 theme desmoglein-2 21:32 arg1 adhesion 74:81 desmoglein-2 and intestinal epithelial intercellular adhesion 21:81 desmoglein-2 and intestinal epithelial intercellular adhesion 21:81 Galectin-3 regulates desmoglein-2 and intestinal epithelial intercellular adhesion. 24567334 5 24 with incubation 532:541 arg1 disaccharide 580:591 a galactose-containing disaccharide 557:591 a galactose-containing disaccharide that competitively inhibits galectin binding to Dsg2 557:644 Down-regulation of Gal3 protein or incubation with lactose, a galactose-containing disaccharide that competitively inhibits galectin binding to Dsg2, decreased intercellular adhesion in intestinal epithelial cells. 24567334 5 24 with incubation 532:541 arg1 lactose 548:554 lactose 548:554 lactose 548:554 Down-regulation of Gal3 protein or incubation with lactose, a galactose-containing disaccharide that competitively inhibits galectin binding to Dsg2, decreased intercellular adhesion in intestinal epithelial cells. 24567334 4 25 from β-galactosides 403:416 arg1 domain 440:445 Dsg2 extracellular domain 421:445 Dsg2 extracellular domain 421:445 Gal3 bound to N-linked β-galactosides in Dsg2 extracellular domain and co-sedimented with caveolin-1 in lipid rafts. 24567334 0 26 theme epithelial 49:58 arg1 adhesion 74:81 desmoglein-2 and intestinal epithelial intercellular adhesion 21:81 desmoglein-2 and intestinal epithelial intercellular adhesion 21:81 Galectin-3 regulates desmoglein-2 and intestinal epithelial intercellular adhesion. 24567334 7 27 theme Gal3 871:874 arg1 role 863:866 a novel role 855:866 a novel role of Gal3 in stabilizing a desmosomal cadherin and intercellular adhesion in intestinal epithelial cells 855:969 These results report a novel role of Gal3 in stabilizing a desmosomal cadherin and intercellular adhesion in intestinal epithelial cells. 24567334 6 28 theme Dsg2 747:750 arg1 protein 752:758 Dsg2 protein 747:758 Dsg2 protein 747:758 In the absence of functional Gal3, Dsg2 protein was internalized from the plasma membrane and degraded in the proteasome. 24567334 0 29 theme intestinal 38:47 arg1 adhesion 74:81 desmoglein-2 and intestinal epithelial intercellular adhesion 21:81 desmoglein-2 and intestinal epithelial intercellular adhesion 21:81 Galectin-3 regulates desmoglein-2 and intestinal epithelial intercellular adhesion. 24567334 7 30 theme novel 857:861 arg1 role 863:866 a novel role 855:866 a novel role of Gal3 in stabilizing a desmosomal cadherin and intercellular adhesion in intestinal epithelial cells 855:969 These results report a novel role of Gal3 in stabilizing a desmosomal cadherin and intercellular adhesion in intestinal epithelial cells. 24567334 5 31 theme galectin 621:628 arg1 binding 630:636 galectin binding 621:636 galectin binding to Dsg2 621:644 Down-regulation of Gal3 protein or incubation with lactose, a galactose-containing disaccharide that competitively inhibits galectin binding to Dsg2, decreased intercellular adhesion in intestinal epithelial cells. 24567334 2 32 theme epithelial 196:205 arg1 cells 207:211 Human intestinal epithelial cells 179:211 Human intestinal epithelial cells 179:211 Human intestinal epithelial cells express the desmoglein-2 isoform. 24567334 7 33 from cadherin 904:911 arg1 cells 965:969 intestinal epithelial cells 943:969 intestinal epithelial cells 943:969 These results report a novel role of Gal3 in stabilizing a desmosomal cadherin and intercellular adhesion in intestinal epithelial cells. 24567334 0 34 theme intercellular 60:72 arg1 adhesion 74:81 desmoglein-2 and intestinal epithelial intercellular adhesion 21:81 desmoglein-2 and intestinal epithelial intercellular adhesion 21:81 Galectin-3 regulates desmoglein-2 and intestinal epithelial intercellular adhesion. 24567334 4 35 theme N-linked 394:401 arg1 β-galactosides 403:416 N-linked β-galactosides 394:416 N-linked β-galactosides in Dsg2 extracellular domain 394:445 Gal3 bound to N-linked β-galactosides in Dsg2 extracellular domain and co-sedimented with caveolin-1 in lipid rafts. 24567334 1 36 theme strong 148:153 arg1 adhesion 169:176 strong intercellular adhesion 148:176 strong intercellular adhesion 148:176 The desmosomal cadherins, desmogleins, and desmocollins mediate strong intercellular adhesion. 24567334 6 37 theme Gal3 741:744 arg1 absence 719:725 the absence 715:725 the absence of functional Gal3 715:744 In the absence of functional Gal3, Dsg2 protein was internalized from the plasma membrane and degraded in the proteasome. 24567334 4 38 from caveolin-1 470:479 arg1 rafts 490:494 lipid rafts 484:494 lipid rafts 484:494 Gal3 bound to N-linked β-galactosides in Dsg2 extracellular domain and co-sedimented with caveolin-1 in lipid rafts. 24567334 7 39 theme intestinal 943:952 arg1 cells 965:969 intestinal epithelial cells 943:969 intestinal epithelial cells 943:969 These results report a novel role of Gal3 in stabilizing a desmosomal cadherin and intercellular adhesion in intestinal epithelial cells. 24567334 1 40 theme intercellular 155:167 arg1 adhesion 169:176 strong intercellular adhesion 148:176 strong intercellular adhesion 148:176 The desmosomal cadherins, desmogleins, and desmocollins mediate strong intercellular adhesion. 24567334 6 41 theme functional 730:739 arg1 Gal3 741:744 functional Gal3 730:744 functional Gal3 730:744 In the absence of functional Gal3, Dsg2 protein was internalized from the plasma membrane and degraded in the proteasome. 24567334 4 42 theme lipid 484:488 arg1 rafts 490:494 lipid rafts 484:494 lipid rafts 484:494 Gal3 bound to N-linked β-galactosides in Dsg2 extracellular domain and co-sedimented with caveolin-1 in lipid rafts. 24567334 5 43 theme Gal3 516:519 arg1 protein 521:527 Gal3 protein 516:527 Gal3 protein 516:527 Down-regulation of Gal3 protein or incubation with lactose, a galactose-containing disaccharide that competitively inhibits galectin binding to Dsg2, decreased intercellular adhesion in intestinal epithelial cells. 29248112 8 0 theme ER 1277:1278 arg1 pathway 1300:1306 ER stress-mediated CWI pathway 1277:1306 ER stress-mediated CWI pathway in C. glabrata 1277:1321 Furthermore, we demonstrated that ER stress-mediated CWI pathway in C. glabrata is also induced by the disruption of other genes encoding proteins that function in a correlated manner in the quality control of N-linked glycoproteins in the ER. 29248112 8 1 theme quality 1434:1440 arg1 control 1442:1448 the quality control 1430:1448 the quality control of N-linked glycoproteins in the ER 1430:1484 Furthermore, we demonstrated that ER stress-mediated CWI pathway in C. glabrata is also induced by the disruption of other genes encoding proteins that function in a correlated manner in the quality control of N-linked glycoproteins in the ER. 29248112 9 2 theme C. 1597:1598 arg1 glabrata 1600:1607 C. glabrata 1597:1607 C. glabrata 1597:1607 These results suggest that calcineurin and ER quality control system act as a platform for maintaining CWI in C. glabrata. 29248112 8 3 theme stress-mediated 1280:1294 arg1 pathway 1300:1306 ER stress-mediated CWI pathway 1277:1306 ER stress-mediated CWI pathway in C. glabrata 1277:1321 Furthermore, we demonstrated that ER stress-mediated CWI pathway in C. glabrata is also induced by the disruption of other genes encoding proteins that function in a correlated manner in the quality control of N-linked glycoproteins in the ER. 29248112 3 4 from maintenance 494:504 arg1 glabrata 512:519 C. glabrata 509:519 C. glabrata 509:519 In numerous fungi, cell wall modulation is reported to be controlled by endoplasmic reticulum (ER) stress, but how the latter affects CWI maintenance in C. glabrata is not clearly understood. 29248112 6 5 theme ER 939:940 arg1 tunicamycin 957:967 the typical ER stress inducer tunicamycin 927:967 the typical ER stress inducer tunicamycin 927:967 Conversely, a treatment with the typical ER stress inducer tunicamycin up-regulated the production of cell wall chitin but did not affect β-1,6-glucan content. 29248112 8 6 theme N-linked 1453:1460 arg1 glycoproteins 1462:1474 N-linked glycoproteins 1453:1474 N-linked glycoproteins in the ER 1453:1484 Furthermore, we demonstrated that ER stress-mediated CWI pathway in C. glabrata is also induced by the disruption of other genes encoding proteins that function in a correlated manner in the quality control of N-linked glycoproteins in the ER. 29248112 5 7 from reduction 832:840 arg1 content 862:868 the β-1,6-glucan content 845:868 the β-1,6-glucan content 845:868 Disruption of cne1 induced ER stress and caused changes in the normal cell wall structure, specifically a reduction in the β-1,6-glucan content and accumulation of chitin. 29248112 1 8 theme second 155:160 arg1 source 174:179 the second most common source 151:179 the second most common source of Candida infections in humans 151:211 Candida glabrata is the second most common source of Candida infections in humans. 29248112 1 8 theme second 155:160 arg1 glabrata 139:146 Candida glabrata 131:146 Candida glabrata 131:146 Candida glabrata is the second most common source of Candida infections in humans. 29248112 6 9 theme typical 931:937 arg1 tunicamycin 957:967 the typical ER stress inducer tunicamycin 927:967 the typical ER stress inducer tunicamycin 927:967 Conversely, a treatment with the typical ER stress inducer tunicamycin up-regulated the production of cell wall chitin but did not affect β-1,6-glucan content. 29248112 0 10 theme wall 95:98 arg1 integrity 100:108 cell wall integrity 90:108 cell wall integrity 90:108 Cooperation between ER stress and calcineurin signaling contributes to the maintenance of cell wall integrity in Candida glabrata. 29248112 4 11 from mutation 604:611 arg1 gene 625:628 the CNE1 gene 616:628 the CNE1 gene 616:628 Here, we characterized a C. glabrata strain harboring a mutation in the CNE1 gene, which encodes a molecular chaperone associated with nascent glycoprotein maturation in the ER. 29248112 4 12 theme glycoprotein 691:702 arg1 maturation 704:713 nascent glycoprotein maturation 683:713 nascent glycoprotein maturation in the ER 683:723 Here, we characterized a C. glabrata strain harboring a mutation in the CNE1 gene, which encodes a molecular chaperone associated with nascent glycoprotein maturation in the ER. 29248112 0 13 theme cell 90:93 arg1 integrity 100:108 cell wall integrity 90:108 cell wall integrity 90:108 Cooperation between ER stress and calcineurin signaling contributes to the maintenance of cell wall integrity in Candida glabrata. 29248112 9 14 theme ER 1530:1531 arg1 system 1549:1554 ER quality control system 1530:1554 ER quality control system 1530:1554 These results suggest that calcineurin and ER quality control system act as a platform for maintaining CWI in C. glabrata. 29248112 9 14 theme ER 1530:1531 arg1 calcineurin 1514:1524 calcineurin 1514:1524 calcineurin 1514:1524 These results suggest that calcineurin and ER quality control system act as a platform for maintaining CWI in C. glabrata. 29248112 9 14 theme ER 1530:1531 arg1 platform 1565:1572 a platform 1563:1572 a platform for maintaining CWI in C. glabrata 1563:1607 These results suggest that calcineurin and ER quality control system act as a platform for maintaining CWI in C. glabrata. 29248112 2 15 theme integrity 261:269 arg1 maintenance 236:246 the maintenance 232:246 the maintenance of cell wall integrity (CWI) 232:275 In this pathogen, the maintenance of cell wall integrity (CWI) frequently precludes effective pharmacological treatment by antifungal agents. 29248112 8 16 theme CWI 1296:1298 arg1 pathway 1300:1306 ER stress-mediated CWI pathway 1277:1306 ER stress-mediated CWI pathway in C. glabrata 1277:1321 Furthermore, we demonstrated that ER stress-mediated CWI pathway in C. glabrata is also induced by the disruption of other genes encoding proteins that function in a correlated manner in the quality control of N-linked glycoproteins in the ER. 29248112 3 17 theme C. 509:510 arg1 glabrata 512:519 C. glabrata 509:519 C. glabrata 509:519 In numerous fungi, cell wall modulation is reported to be controlled by endoplasmic reticulum (ER) stress, but how the latter affects CWI maintenance in C. glabrata is not clearly understood. 29248112 2 18 theme effective 298:306 arg1 treatment 324:332 effective pharmacological treatment 298:332 effective pharmacological treatment 298:332 In this pathogen, the maintenance of cell wall integrity (CWI) frequently precludes effective pharmacological treatment by antifungal agents. 29248112 4 19 gly glycoprotein 691:702 arg1 glycoprotein 691:702 nascent glycoprotein maturation 683:713 nascent glycoprotein maturation in the ER 683:723 Here, we characterized a C. glabrata strain harboring a mutation in the CNE1 gene, which encodes a molecular chaperone associated with nascent glycoprotein maturation in the ER. 29248112 8 20 link N-linked 1453:1460 arg1 glycoproteins 1462:1474 N-linked glycoproteins 1453:1474 N-linked glycoproteins in the ER 1453:1484 Furthermore, we demonstrated that ER stress-mediated CWI pathway in C. glabrata is also induced by the disruption of other genes encoding proteins that function in a correlated manner in the quality control of N-linked glycoproteins in the ER. 29248112 4 21 theme glabrata 576:583 arg1 strain 585:590 a C. glabrata strain 571:590 a C. glabrata strain harboring a mutation in the CNE1 gene, which encodes a molecular chaperone associated with nascent glycoprotein maturation in the ER 571:723 Here, we characterized a C. glabrata strain harboring a mutation in the CNE1 gene, which encodes a molecular chaperone associated with nascent glycoprotein maturation in the ER. 29248112 2 22 theme wall 256:259 arg1 integrity 261:269 cell wall integrity 251:269 cell wall integrity (CWI) 251:275 In this pathogen, the maintenance of cell wall integrity (CWI) frequently precludes effective pharmacological treatment by antifungal agents. 29248112 2 22 theme wall 256:259 arg1 CWI 272:274 CWI 272:274 CWI 272:274 In this pathogen, the maintenance of cell wall integrity (CWI) frequently precludes effective pharmacological treatment by antifungal agents. 29248112 6 23 theme chitin 1010:1015 arg1 production 986:995 the production 982:995 the production of cell wall chitin 982:1015 Conversely, a treatment with the typical ER stress inducer tunicamycin up-regulated the production of cell wall chitin but did not affect β-1,6-glucan content. 29248112 5 24 theme cell 796:799 arg1 structure 806:814 the normal cell wall structure 785:814 the normal cell wall structure 785:814 Disruption of cne1 induced ER stress and caused changes in the normal cell wall structure, specifically a reduction in the β-1,6-glucan content and accumulation of chitin. 29248112 0 25 theme integrity 100:108 arg1 maintenance 75:85 the maintenance 71:85 the maintenance of cell wall integrity in Candida glabrata 71:128 Cooperation between ER stress and calcineurin signaling contributes to the maintenance of cell wall integrity in Candida glabrata. 29248112 7 26 theme C. 1090:1091 arg1 glabrata 1093:1100 C. glabrata 1090:1100 C. glabrata 1090:1100 Our results also indicated that C. glabrata features a uniquely evolved ER stress-mediated CWI pathway, which differs from that in the closely related species Saccharomyces cerevisiae. 29248112 4 27 from maturation 704:713 arg1 ER 722:723 the ER 718:723 the ER 718:723 Here, we characterized a C. glabrata strain harboring a mutation in the CNE1 gene, which encodes a molecular chaperone associated with nascent glycoprotein maturation in the ER. 29248112 2 28 theme cell 251:254 arg1 integrity 261:269 cell wall integrity 251:269 cell wall integrity (CWI) 251:275 In this pathogen, the maintenance of cell wall integrity (CWI) frequently precludes effective pharmacological treatment by antifungal agents. 29248112 2 28 theme cell 251:254 arg1 CWI 272:274 CWI 272:274 CWI 272:274 In this pathogen, the maintenance of cell wall integrity (CWI) frequently precludes effective pharmacological treatment by antifungal agents. 29248112 8 29 from ER 1483:1484 arg1 control 1442:1448 the quality control 1430:1448 the quality control of N-linked glycoproteins in the ER 1430:1484 Furthermore, we demonstrated that ER stress-mediated CWI pathway in C. glabrata is also induced by the disruption of other genes encoding proteins that function in a correlated manner in the quality control of N-linked glycoproteins in the ER. 29248112 1 30 theme common 167:172 arg1 source 174:179 the second most common source 151:179 the second most common source of Candida infections in humans 151:211 Candida glabrata is the second most common source of Candida infections in humans. 29248112 1 30 theme common 167:172 arg1 glabrata 139:146 Candida glabrata 131:146 Candida glabrata 131:146 Candida glabrata is the second most common source of Candida infections in humans. 29248112 5 31 theme ER 753:754 arg1 stress 756:761 ER stress 753:761 ER stress 753:761 Disruption of cne1 induced ER stress and caused changes in the normal cell wall structure, specifically a reduction in the β-1,6-glucan content and accumulation of chitin. 29248112 4 32 theme nascent 683:689 arg1 maturation 704:713 nascent glycoprotein maturation 683:713 nascent glycoprotein maturation in the ER 683:723 Here, we characterized a C. glabrata strain harboring a mutation in the CNE1 gene, which encodes a molecular chaperone associated with nascent glycoprotein maturation in the ER. 29248112 3 33 theme CWI 490:492 arg1 maintenance 494:504 CWI maintenance 490:504 CWI maintenance in C. glabrata 490:519 In numerous fungi, cell wall modulation is reported to be controlled by endoplasmic reticulum (ER) stress, but how the latter affects CWI maintenance in C. glabrata is not clearly understood. 29248112 4 34 theme CNE1 620:623 arg1 gene 625:628 the CNE1 gene 616:628 the CNE1 gene 616:628 Here, we characterized a C. glabrata strain harboring a mutation in the CNE1 gene, which encodes a molecular chaperone associated with nascent glycoprotein maturation in the ER. 29248112 3 35 theme cell 375:378 arg1 modulation 385:394 cell wall modulation 375:394 cell wall modulation 375:394 In numerous fungi, cell wall modulation is reported to be controlled by endoplasmic reticulum (ER) stress, but how the latter affects CWI maintenance in C. glabrata is not clearly understood. 29248112 8 36 theme C. 1311:1312 arg1 glabrata 1314:1321 C. glabrata 1311:1321 C. glabrata 1311:1321 Furthermore, we demonstrated that ER stress-mediated CWI pathway in C. glabrata is also induced by the disruption of other genes encoding proteins that function in a correlated manner in the quality control of N-linked glycoproteins in the ER. 29248112 6 37 theme wall 1005:1008 arg1 chitin 1010:1015 cell wall chitin 1000:1015 cell wall chitin 1000:1015 Conversely, a treatment with the typical ER stress inducer tunicamycin up-regulated the production of cell wall chitin but did not affect β-1,6-glucan content. 29248112 3 38 theme numerous 359:366 arg1 fungi 368:372 numerous fungi 359:372 numerous fungi 359:372 In numerous fungi, cell wall modulation is reported to be controlled by endoplasmic reticulum (ER) stress, but how the latter affects CWI maintenance in C. glabrata is not clearly understood. 29248112 5 39 theme chitin 890:895 arg1 reduction 832:840 a reduction 830:840 a reduction in the β-1,6-glucan content 830:868 Disruption of cne1 induced ER stress and caused changes in the normal cell wall structure, specifically a reduction in the β-1,6-glucan content and accumulation of chitin. 29248112 5 39 theme chitin 890:895 arg1 accumulation 874:885 accumulation 874:885 accumulation of chitin 874:895 Disruption of cne1 induced ER stress and caused changes in the normal cell wall structure, specifically a reduction in the β-1,6-glucan content and accumulation of chitin. 29248112 1 40 theme Candida 184:190 arg1 infections 192:201 Candida infections 184:201 Candida infections 184:201 Candida glabrata is the second most common source of Candida infections in humans. 29248112 0 41 theme ER 20:21 arg1 stress 23:28 ER stress 20:28 ER stress 20:28 Cooperation between ER stress and calcineurin signaling contributes to the maintenance of cell wall integrity in Candida glabrata. 29248112 8 42 theme glycoproteins 1462:1474 arg1 control 1442:1448 the quality control 1430:1448 the quality control of N-linked glycoproteins in the ER 1430:1484 Furthermore, we demonstrated that ER stress-mediated CWI pathway in C. glabrata is also induced by the disruption of other genes encoding proteins that function in a correlated manner in the quality control of N-linked glycoproteins in the ER. 29248112 0 43 theme Candida 113:119 arg1 glabrata 121:128 Candida glabrata 113:128 Candida glabrata 113:128 Cooperation between ER stress and calcineurin signaling contributes to the maintenance of cell wall integrity in Candida glabrata. 29248112 2 44 theme antifungal 337:346 arg1 agents 348:353 antifungal agents 337:353 antifungal agents 337:353 In this pathogen, the maintenance of cell wall integrity (CWI) frequently precludes effective pharmacological treatment by antifungal agents. 29248112 1 45 theme infections 192:201 arg1 source 174:179 the second most common source 151:179 the second most common source of Candida infections in humans 151:211 Candida glabrata is the second most common source of Candida infections in humans. 29248112 1 45 theme infections 192:201 arg1 glabrata 139:146 Candida glabrata 131:146 Candida glabrata 131:146 Candida glabrata is the second most common source of Candida infections in humans. 29248112 0 46 theme calcineurin 34:44 arg1 signaling 46:54 calcineurin signaling 34:54 calcineurin signaling 34:54 Cooperation between ER stress and calcineurin signaling contributes to the maintenance of cell wall integrity in Candida glabrata. 29248112 0 47 from maintenance 75:85 arg1 glabrata 121:128 Candida glabrata 113:128 Candida glabrata 113:128 Cooperation between ER stress and calcineurin signaling contributes to the maintenance of cell wall integrity in Candida glabrata. 29248112 9 48 theme quality 1533:1539 arg1 system 1549:1554 ER quality control system 1530:1554 ER quality control system 1530:1554 These results suggest that calcineurin and ER quality control system act as a platform for maintaining CWI in C. glabrata. 29248112 9 48 theme quality 1533:1539 arg1 calcineurin 1514:1524 calcineurin 1514:1524 calcineurin 1514:1524 These results suggest that calcineurin and ER quality control system act as a platform for maintaining CWI in C. glabrata. 29248112 9 48 theme quality 1533:1539 arg1 platform 1565:1572 a platform 1563:1572 a platform for maintaining CWI in C. glabrata 1563:1607 These results suggest that calcineurin and ER quality control system act as a platform for maintaining CWI in C. glabrata. 29248112 3 49 theme endoplasmic 428:438 arg1 reticulum 440:448 endoplasmic reticulum 428:448 endoplasmic reticulum (ER) stress 428:460 In numerous fungi, cell wall modulation is reported to be controlled by endoplasmic reticulum (ER) stress, but how the latter affects CWI maintenance in C. glabrata is not clearly understood. 29248112 3 49 theme endoplasmic 428:438 arg1 ER 451:452 ER 451:452 ER 451:452 In numerous fungi, cell wall modulation is reported to be controlled by endoplasmic reticulum (ER) stress, but how the latter affects CWI maintenance in C. glabrata is not clearly understood. 29248112 6 50 theme inducer 949:955 arg1 tunicamycin 957:967 the typical ER stress inducer tunicamycin 927:967 the typical ER stress inducer tunicamycin 927:967 Conversely, a treatment with the typical ER stress inducer tunicamycin up-regulated the production of cell wall chitin but did not affect β-1,6-glucan content. 29248112 3 51 theme reticulum 440:448 arg1 stress 455:460 endoplasmic reticulum (ER) stress 428:460 endoplasmic reticulum (ER) stress 428:460 In numerous fungi, cell wall modulation is reported to be controlled by endoplasmic reticulum (ER) stress, but how the latter affects CWI maintenance in C. glabrata is not clearly understood. 29248112 3 52 theme wall 380:383 arg1 modulation 385:394 cell wall modulation 375:394 cell wall modulation 375:394 In numerous fungi, cell wall modulation is reported to be controlled by endoplasmic reticulum (ER) stress, but how the latter affects CWI maintenance in C. glabrata is not clearly understood. 29248112 7 53 theme CWI 1149:1151 arg1 pathway 1153:1159 a uniquely evolved ER stress-mediated CWI pathway 1111:1159 a uniquely evolved ER stress-mediated CWI pathway 1111:1159 Our results also indicated that C. glabrata features a uniquely evolved ER stress-mediated CWI pathway, which differs from that in the closely related species Saccharomyces cerevisiae. 29248112 6 54 with treatment 912:920 arg1 tunicamycin 957:967 the typical ER stress inducer tunicamycin 927:967 the typical ER stress inducer tunicamycin 927:967 Conversely, a treatment with the typical ER stress inducer tunicamycin up-regulated the production of cell wall chitin but did not affect β-1,6-glucan content. 29248112 8 55 from pathway 1300:1306 arg1 glabrata 1314:1321 C. glabrata 1311:1321 C. glabrata 1311:1321 Furthermore, we demonstrated that ER stress-mediated CWI pathway in C. glabrata is also induced by the disruption of other genes encoding proteins that function in a correlated manner in the quality control of N-linked glycoproteins in the ER. 29248112 4 56 theme molecular 647:655 arg1 chaperone 657:665 a molecular chaperone 645:665 a molecular chaperone associated with nascent glycoprotein maturation in the ER 645:723 Here, we characterized a C. glabrata strain harboring a mutation in the CNE1 gene, which encodes a molecular chaperone associated with nascent glycoprotein maturation in the ER. 29248112 4 56 theme molecular 647:655 arg1 mutation 604:611 a mutation 602:611 a mutation 602:611 Here, we characterized a C. glabrata strain harboring a mutation in the CNE1 gene, which encodes a molecular chaperone associated with nascent glycoprotein maturation in the ER. 29248112 8 57 from glycoproteins 1462:1474 arg1 ER 1483:1484 the ER 1479:1484 the ER 1479:1484 Furthermore, we demonstrated that ER stress-mediated CWI pathway in C. glabrata is also induced by the disruption of other genes encoding proteins that function in a correlated manner in the quality control of N-linked glycoproteins in the ER. 29248112 7 58 theme stress-mediated 1133:1147 arg1 pathway 1153:1159 a uniquely evolved ER stress-mediated CWI pathway 1111:1159 a uniquely evolved ER stress-mediated CWI pathway 1111:1159 Our results also indicated that C. glabrata features a uniquely evolved ER stress-mediated CWI pathway, which differs from that in the closely related species Saccharomyces cerevisiae. 29248112 5 59 from changes 774:780 arg1 structure 806:814 the normal cell wall structure 785:814 the normal cell wall structure 785:814 Disruption of cne1 induced ER stress and caused changes in the normal cell wall structure, specifically a reduction in the β-1,6-glucan content and accumulation of chitin. 29248112 5 60 theme β-1,6-glucan 849:860 arg1 content 862:868 the β-1,6-glucan content 845:868 the β-1,6-glucan content 845:868 Disruption of cne1 induced ER stress and caused changes in the normal cell wall structure, specifically a reduction in the β-1,6-glucan content and accumulation of chitin. 29248112 8 61 from control 1442:1448 arg1 ER 1483:1484 the ER 1479:1484 the ER 1479:1484 Furthermore, we demonstrated that ER stress-mediated CWI pathway in C. glabrata is also induced by the disruption of other genes encoding proteins that function in a correlated manner in the quality control of N-linked glycoproteins in the ER. 29248112 9 62 from CWI 1590:1592 arg1 glabrata 1600:1607 C. glabrata 1597:1607 C. glabrata 1597:1607 These results suggest that calcineurin and ER quality control system act as a platform for maintaining CWI in C. glabrata. 29248112 8 63 theme correlated 1409:1418 arg1 manner 1420:1425 a correlated manner 1407:1425 a correlated manner 1407:1425 Furthermore, we demonstrated that ER stress-mediated CWI pathway in C. glabrata is also induced by the disruption of other genes encoding proteins that function in a correlated manner in the quality control of N-linked glycoproteins in the ER. 29248112 8 64 theme genes 1366:1370 arg1 disruption 1346:1355 the disruption 1342:1355 the disruption of other genes encoding proteins that function in a correlated manner in the quality control of N-linked glycoproteins in the ER 1342:1484 Furthermore, we demonstrated that ER stress-mediated CWI pathway in C. glabrata is also induced by the disruption of other genes encoding proteins that function in a correlated manner in the quality control of N-linked glycoproteins in the ER. 29248112 9 65 theme control 1541:1547 arg1 system 1549:1554 ER quality control system 1530:1554 ER quality control system 1530:1554 These results suggest that calcineurin and ER quality control system act as a platform for maintaining CWI in C. glabrata. 29248112 9 65 theme control 1541:1547 arg1 calcineurin 1514:1524 calcineurin 1514:1524 calcineurin 1514:1524 These results suggest that calcineurin and ER quality control system act as a platform for maintaining CWI in C. glabrata. 29248112 9 65 theme control 1541:1547 arg1 platform 1565:1572 a platform 1563:1572 a platform for maintaining CWI in C. glabrata 1563:1607 These results suggest that calcineurin and ER quality control system act as a platform for maintaining CWI in C. glabrata. 29248112 2 66 theme pharmacological 308:322 arg1 treatment 324:332 effective pharmacological treatment 298:332 effective pharmacological treatment 298:332 In this pathogen, the maintenance of cell wall integrity (CWI) frequently precludes effective pharmacological treatment by antifungal agents. 29248112 8 67 theme other 1360:1364 arg1 genes 1366:1370 other genes 1360:1370 other genes encoding proteins that function in a correlated manner in the quality control of N-linked glycoproteins in the ER 1360:1484 Furthermore, we demonstrated that ER stress-mediated CWI pathway in C. glabrata is also induced by the disruption of other genes encoding proteins that function in a correlated manner in the quality control of N-linked glycoproteins in the ER. 29248112 1 68 from source 174:179 arg1 humans 206:211 humans 206:211 humans 206:211 Candida glabrata is the second most common source of Candida infections in humans. 29248112 1 69 theme Candida 131:137 arg1 source 174:179 the second most common source 151:179 the second most common source of Candida infections in humans 151:211 Candida glabrata is the second most common source of Candida infections in humans. 29248112 1 69 theme Candida 131:137 arg1 glabrata 139:146 Candida glabrata 131:146 Candida glabrata 131:146 Candida glabrata is the second most common source of Candida infections in humans. 29248112 5 70 from accumulation 874:885 arg1 content 862:868 the β-1,6-glucan content 845:868 the β-1,6-glucan content 845:868 Disruption of cne1 induced ER stress and caused changes in the normal cell wall structure, specifically a reduction in the β-1,6-glucan content and accumulation of chitin. 29248112 7 71 theme related 1201:1207 arg1 species 1209:1215 the closely related species 1189:1215 the closely related species 1189:1215 Our results also indicated that C. glabrata features a uniquely evolved ER stress-mediated CWI pathway, which differs from that in the closely related species Saccharomyces cerevisiae. 29248112 5 72 theme normal 789:794 arg1 structure 806:814 the normal cell wall structure 785:814 the normal cell wall structure 785:814 Disruption of cne1 induced ER stress and caused changes in the normal cell wall structure, specifically a reduction in the β-1,6-glucan content and accumulation of chitin. 29248112 6 73 theme cell 1000:1003 arg1 chitin 1010:1015 cell wall chitin 1000:1015 cell wall chitin 1000:1015 Conversely, a treatment with the typical ER stress inducer tunicamycin up-regulated the production of cell wall chitin but did not affect β-1,6-glucan content. 29248112 8 74 gly glycoproteins 1462:1474 arg1 glycoproteins 1462:1474 N-linked glycoproteins 1453:1474 N-linked glycoproteins in the ER 1453:1484 Furthermore, we demonstrated that ER stress-mediated CWI pathway in C. glabrata is also induced by the disruption of other genes encoding proteins that function in a correlated manner in the quality control of N-linked glycoproteins in the ER. 29248112 5 75 theme wall 801:804 arg1 structure 806:814 the normal cell wall structure 785:814 the normal cell wall structure 785:814 Disruption of cne1 induced ER stress and caused changes in the normal cell wall structure, specifically a reduction in the β-1,6-glucan content and accumulation of chitin. 29248112 4 76 theme C. 573:574 arg1 strain 585:590 a C. glabrata strain 571:590 a C. glabrata strain harboring a mutation in the CNE1 gene, which encodes a molecular chaperone associated with nascent glycoprotein maturation in the ER 571:723 Here, we characterized a C. glabrata strain harboring a mutation in the CNE1 gene, which encodes a molecular chaperone associated with nascent glycoprotein maturation in the ER. 29248112 5 77 theme cne1 740:743 arg1 Disruption 726:735 Disruption 726:735 Disruption of cne1 726:743 Disruption of cne1 induced ER stress and caused changes in the normal cell wall structure, specifically a reduction in the β-1,6-glucan content and accumulation of chitin. 29248112 7 78 theme ER 1130:1131 arg1 pathway 1153:1159 a uniquely evolved ER stress-mediated CWI pathway 1111:1159 a uniquely evolved ER stress-mediated CWI pathway 1111:1159 Our results also indicated that C. glabrata features a uniquely evolved ER stress-mediated CWI pathway, which differs from that in the closely related species Saccharomyces cerevisiae. 29248112 6 79 theme β-1,6-glucan 1036:1047 arg1 content 1049:1055 β-1,6-glucan content 1036:1055 β-1,6-glucan content 1036:1055 Conversely, a treatment with the typical ER stress inducer tunicamycin up-regulated the production of cell wall chitin but did not affect β-1,6-glucan content. 29248112 7 80 theme evolved 1122:1128 arg1 pathway 1153:1159 a uniquely evolved ER stress-mediated CWI pathway 1111:1159 a uniquely evolved ER stress-mediated CWI pathway 1111:1159 Our results also indicated that C. glabrata features a uniquely evolved ER stress-mediated CWI pathway, which differs from that in the closely related species Saccharomyces cerevisiae. 29248112 6 81 theme stress 942:947 arg1 tunicamycin 957:967 the typical ER stress inducer tunicamycin 927:967 the typical ER stress inducer tunicamycin 927:967 Conversely, a treatment with the typical ER stress inducer tunicamycin up-regulated the production of cell wall chitin but did not affect β-1,6-glucan content. 29113996 6 0 theme functional 1354:1363 arg1 pathways 1375:1382 the functional signaling pathways 1350:1382 the functional signaling pathways 1350:1382 Using bioinformatics we analyzed the functional signaling pathways during GSIS, including well-known insulin secretion pathways. 29113996 6 0 theme functional 1354:1363 arg1 pathways 1436:1443 well-known insulin secretion pathways 1407:1443 well-known insulin secretion pathways 1407:1443 Using bioinformatics we analyzed the functional signaling pathways during GSIS, including well-known insulin secretion pathways. 29113996 3 1 theme mechanisms 547:556 arg1 understanding 486:498 our understanding 482:498 our understanding of glucose-stimulated insulin secretion (GSIS) mechanisms 482:556 Improving our understanding of glucose-stimulated insulin secretion (GSIS) mechanisms under normal conditions is a prerequisite for developing better interventions against diabetes. 29113996 1 2 theme blood 286:290 arg1 levels 300:305 elevated blood glucose levels 277:305 elevated blood glucose levels 277:305 Normal pancreatic islet β-cells (PBCs) abundantly secrete insulin in response to elevated blood glucose levels, in order to maintain an adequate control of energy balance and glucose homeostasis. 29113996 7 3 theme min 1568:1570 arg1 GSIS 1572:1575 15 min GSIS 1565:1575 15 min GSIS 1565:1575 Furthermore, we identified six novel activated signaling pathways (e.g. agrin interactions and prolactin signaling) at 15 min GSIS, which may increase our understanding of the molecular mechanism underlying GSIS. 29113996 8 4 theme reaction 1729:1736 arg1 monitoring 1738:1747 parallel reaction monitoring 1720:1747 parallel reaction monitoring 1720:1747 Moreover, we validated some of the regulated phosphosites by parallel reaction monitoring, which resulted in the validation of eleven new phosphosites significantly regulated on GSIS. 29113996 8 5 theme new 1793:1795 arg1 phosphosites 1797:1808 eleven new phosphosites 1786:1808 eleven new phosphosites significantly regulated on GSIS 1786:1840 Moreover, we validated some of the regulated phosphosites by parallel reaction monitoring, which resulted in the validation of eleven new phosphosites significantly regulated on GSIS. 29113996 5 6 theme SA 1272:1273 arg1 glycopeptides 1275:1287 SA glycopeptides 1272:1287 SA glycopeptides 1272:1287 The isolated islets were subjected to time-resolved quantitative phosphoproteomics and sialiomics using iTRAQ-labeling combined with enrichment of phosphorylated peptides and formerly SA glycopeptides and high-accuracy LC-MS/MS. 29113996 4 7 theme Langerhans 917:926 arg1 proteins 855:862 phosphorylated proteins 840:862 phosphorylated proteins 840:862 Here, we aimed at identifying novel signaling pathways involved in the initial release of insulin from PBCs after glucose stimulation using quantitative strategies for the assessment of phosphorylated proteins and sialylated N-linked (SA) glycoproteins.Islets of Langerhans derived from newborn rats with a subsequent 9-10 days of maturation in vitro were stimulated with 20 mm glucose for 0 min (control), 5 min, 10 min, and 15 min. 29113996 4 7 theme Langerhans 917:926 arg1 glycoproteins.Islets 893:912 sialylated N-linked (SA) glycoproteins.Islets 868:912 sialylated N-linked (SA) glycoproteins.Islets of Langerhans derived from newborn rats with a subsequent 9-10 days of maturation in vitro were stimulated with 20 mm glucose for 0 min (control), 5 min, 10 min, and 15 min 868:1085 Here, we aimed at identifying novel signaling pathways involved in the initial release of insulin from PBCs after glucose stimulation using quantitative strategies for the assessment of phosphorylated proteins and sialylated N-linked (SA) glycoproteins.Islets of Langerhans derived from newborn rats with a subsequent 9-10 days of maturation in vitro were stimulated with 20 mm glucose for 0 min (control), 5 min, 10 min, and 15 min. 29113996 10 8 theme cell-ECM 2039:2046 arg1 interaction 2048:2058 cell-ECM interaction 2039:2058 cell-ECM interaction 2039:2058 Interestingly, proteins important for cell-cell interaction, cell movement, cell-ECM interaction and Focal Adhesion (e.g. integrins, semaphorins, and plexins) were found regulated at the level of sialylation, but not in protein expression. 29113996 5 9 theme peptides 1250:1257 arg1 enrichment 1221:1230 enrichment 1221:1230 enrichment of phosphorylated peptides and formerly SA glycopeptides and high-accuracy LC-MS/MS 1221:1314 The isolated islets were subjected to time-resolved quantitative phosphoproteomics and sialiomics using iTRAQ-labeling combined with enrichment of phosphorylated peptides and formerly SA glycopeptides and high-accuracy LC-MS/MS. 29113996 7 10 dep identified 1462:1471 arg1 increase 1588:1595 increase 1588:1595 may increase our understanding of the molecular mechanism underlying GSIS 1584:1656 Furthermore, we identified six novel activated signaling pathways (e.g. agrin interactions and prolactin signaling) at 15 min GSIS, which may increase our understanding of the molecular mechanism underlying GSIS. 29113996 4 11 theme subsequent 961:970 arg1 days 977:980 a subsequent 9-10 days 959:980 a subsequent 9-10 days of maturation in vitro 959:1003 Here, we aimed at identifying novel signaling pathways involved in the initial release of insulin from PBCs after glucose stimulation using quantitative strategies for the assessment of phosphorylated proteins and sialylated N-linked (SA) glycoproteins.Islets of Langerhans derived from newborn rats with a subsequent 9-10 days of maturation in vitro were stimulated with 20 mm glucose for 0 min (control), 5 min, 10 min, and 15 min. 29113996 4 12 theme initial 725:731 arg1 release 733:739 the initial release 721:739 the initial release of insulin from PBCs after glucose stimulation using quantitative strategies for the assessment of phosphorylated proteins and sialylated N-linked (SA) glycoproteins.Islets of Langerhans derived from newborn rats with a subsequent 9-10 days of maturation in vitro were stimulated with 20 mm glucose for 0 min (control), 5 min, 10 min, and 15 min 721:1085 Here, we aimed at identifying novel signaling pathways involved in the initial release of insulin from PBCs after glucose stimulation using quantitative strategies for the assessment of phosphorylated proteins and sialylated N-linked (SA) glycoproteins.Islets of Langerhans derived from newborn rats with a subsequent 9-10 days of maturation in vitro were stimulated with 20 mm glucose for 0 min (control), 5 min, 10 min, and 15 min. 29113996 7 13 theme activated 1483:1491 arg1 pathways 1503:1510 six novel activated signaling pathways 1473:1510 six novel activated signaling pathways (e.g. agrin interactions and prolactin signaling) 1473:1560 Furthermore, we identified six novel activated signaling pathways (e.g. agrin interactions and prolactin signaling) at 15 min GSIS, which may increase our understanding of the molecular mechanism underlying GSIS. 29113996 11 14 theme underlying 2407:2416 arg1 GSIS 2418:2421 the complex signaling underlying GSIS 2385:2421 the complex signaling underlying GSIS 2385:2421 Collectively, we believe that this comprehensive Proteomics and PTMomics survey of signaling pathways taking place during brief GSIS of primary PBCs is contributing to understanding the complex signaling underlying GSIS. 29113996 4 15 theme novel 684:688 arg1 pathways 700:707 novel signaling pathways 684:707 novel signaling pathways involved in the initial release of insulin from PBCs after glucose stimulation using quantitative strategies for the assessment of phosphorylated proteins and sialylated N-linked (SA) glycoproteins.Islets of Langerhans derived from newborn rats with a subsequent 9-10 days of maturation in vitro were stimulated with 20 mm glucose for 0 min (control), 5 min, 10 min, and 15 min 684:1085 Here, we aimed at identifying novel signaling pathways involved in the initial release of insulin from PBCs after glucose stimulation using quantitative strategies for the assessment of phosphorylated proteins and sialylated N-linked (SA) glycoproteins.Islets of Langerhans derived from newborn rats with a subsequent 9-10 days of maturation in vitro were stimulated with 20 mm glucose for 0 min (control), 5 min, 10 min, and 15 min. 29113996 6 16 theme insulin 1418:1424 arg1 secretion 1426:1434 well-known insulin secretion 1407:1434 well-known insulin secretion pathways 1407:1443 Using bioinformatics we analyzed the functional signaling pathways during GSIS, including well-known insulin secretion pathways. 29113996 10 17 dep found 2127:2131 arg1 regulated 2133:2141 regulated 2133:2141 regulated at the level of sialylation, but not in protein expression 2133:2200 Interestingly, proteins important for cell-cell interaction, cell movement, cell-ECM interaction and Focal Adhesion (e.g. integrins, semaphorins, and plexins) were found regulated at the level of sialylation, but not in protein expression. 29113996 11 18 theme complex 2389:2395 arg1 GSIS 2418:2421 the complex signaling underlying GSIS 2385:2421 the complex signaling underlying GSIS 2385:2421 Collectively, we believe that this comprehensive Proteomics and PTMomics survey of signaling pathways taking place during brief GSIS of primary PBCs is contributing to understanding the complex signaling underlying GSIS. 29113996 0 19 theme Proteomics 173:182 arg1 PTMomics 185:192 Post-translational Modification Specific Proteomics (PTMomics) 132:193 Post-translational Modification Specific Proteomics (PTMomics) 132:193 Characterization of the Molecular Mechanisms Underlying Glucose Stimulated Insulin Secretion from Isolated Pancreatic β-cells Using Post-translational Modification Specific Proteomics (PTMomics). 29113996 9 20 theme SA 1890:1891 arg1 glycosylation 1893:1905 SA glycosylation 1890:1905 SA glycosylation 1890:1905 Besides protein phosphorylation, alteration in SA glycosylation was observed on several surface proteins on brief GSIS. 29113996 9 21 from proteins 1939:1946 arg1 GSIS 1957:1960 brief GSIS 1951:1960 brief GSIS 1951:1960 Besides protein phosphorylation, alteration in SA glycosylation was observed on several surface proteins on brief GSIS. 29113996 1 22 dep levels 300:305 arg1 response 265:272 response 265:272 response 265:272 Normal pancreatic islet β-cells (PBCs) abundantly secrete insulin in response to elevated blood glucose levels, in order to maintain an adequate control of energy balance and glucose homeostasis. 29113996 0 23 theme Insulin 75:81 arg1 Secretion 83:91 Glucose Stimulated Insulin Secretion 56:91 Glucose Stimulated Insulin Secretion from Isolated Pancreatic β-cells 56:124 Characterization of the Molecular Mechanisms Underlying Glucose Stimulated Insulin Secretion from Isolated Pancreatic β-cells Using Post-translational Modification Specific Proteomics (PTMomics). 29113996 5 24 theme time-resolved 1126:1138 arg1 phosphoproteomics 1153:1169 time-resolved quantitative phosphoproteomics 1126:1169 time-resolved quantitative phosphoproteomics 1126:1169 The isolated islets were subjected to time-resolved quantitative phosphoproteomics and sialiomics using iTRAQ-labeling combined with enrichment of phosphorylated peptides and formerly SA glycopeptides and high-accuracy LC-MS/MS. 29113996 10 25 dep integrins 2085:2093 arg1 e.g. 2080:2083 e.g. 2080:2083 e.g. 2080:2083 Interestingly, proteins important for cell-cell interaction, cell movement, cell-ECM interaction and Focal Adhesion (e.g. integrins, semaphorins, and plexins) were found regulated at the level of sialylation, but not in protein expression. 29113996 1 26 theme balance 359:365 arg1 control 341:347 an adequate control 329:347 an adequate control of energy balance and glucose homeostasis 329:389 Normal pancreatic islet β-cells (PBCs) abundantly secrete insulin in response to elevated blood glucose levels, in order to maintain an adequate control of energy balance and glucose homeostasis. 29113996 1 27 theme Normal 196:201 arg1 β-cells 220:226 Normal pancreatic islet β-cells 196:226 Normal pancreatic islet β-cells (PBCs) 196:233 Normal pancreatic islet β-cells (PBCs) abundantly secrete insulin in response to elevated blood glucose levels, in order to maintain an adequate control of energy balance and glucose homeostasis. 29113996 1 27 theme Normal 196:201 arg1 PBCs 229:232 PBCs 229:232 PBCs 229:232 Normal pancreatic islet β-cells (PBCs) abundantly secrete insulin in response to elevated blood glucose levels, in order to maintain an adequate control of energy balance and glucose homeostasis. 29113996 4 28 attach derived 928:934 arg2 glycoproteins.Islets 893:912 sialylated N-linked (SA) glycoproteins.Islets 868:912 sialylated N-linked (SA) glycoproteins.Islets of Langerhans derived from newborn rats with a subsequent 9-10 days of maturation in vitro were stimulated with 20 mm glucose for 0 min (control), 5 min, 10 min, and 15 min 868:1085 Here, we aimed at identifying novel signaling pathways involved in the initial release of insulin from PBCs after glucose stimulation using quantitative strategies for the assessment of phosphorylated proteins and sialylated N-linked (SA) glycoproteins.Islets of Langerhans derived from newborn rats with a subsequent 9-10 days of maturation in vitro were stimulated with 20 mm glucose for 0 min (control), 5 min, 10 min, and 15 min. 29113996 4 28 attach derived 928:934 arg1 rats 949:952 newborn rats 941:952 newborn rats with a subsequent 9-10 days of maturation in vitro were stimulated with 20 mm glucose for 0 min (control), 5 min, 10 min, and 15 min 941:1085 Here, we aimed at identifying novel signaling pathways involved in the initial release of insulin from PBCs after glucose stimulation using quantitative strategies for the assessment of phosphorylated proteins and sialylated N-linked (SA) glycoproteins.Islets of Langerhans derived from newborn rats with a subsequent 9-10 days of maturation in vitro were stimulated with 20 mm glucose for 0 min (control), 5 min, 10 min, and 15 min. 29113996 11 29 theme primary 2339:2345 arg1 PBCs 2347:2350 primary PBCs 2339:2350 primary PBCs 2339:2350 Collectively, we believe that this comprehensive Proteomics and PTMomics survey of signaling pathways taking place during brief GSIS of primary PBCs is contributing to understanding the complex signaling underlying GSIS. 29113996 5 30 gly glycopeptides 1275:1287 arg2 glycopeptides 1275:1287 SA glycopeptides 1272:1287 SA glycopeptides 1272:1287 The isolated islets were subjected to time-resolved quantitative phosphoproteomics and sialiomics using iTRAQ-labeling combined with enrichment of phosphorylated peptides and formerly SA glycopeptides and high-accuracy LC-MS/MS. 29113996 0 31 theme Pancreatic 107:116 arg1 β-cells 118:124 Isolated Pancreatic β-cells 98:124 Isolated Pancreatic β-cells 98:124 Characterization of the Molecular Mechanisms Underlying Glucose Stimulated Insulin Secretion from Isolated Pancreatic β-cells Using Post-translational Modification Specific Proteomics (PTMomics). 29113996 1 32 theme glucose 371:377 arg1 homeostasis 379:389 glucose homeostasis 371:389 glucose homeostasis 371:389 Normal pancreatic islet β-cells (PBCs) abundantly secrete insulin in response to elevated blood glucose levels, in order to maintain an adequate control of energy balance and glucose homeostasis. 29113996 4 33 theme mm 1029:1030 arg1 glucose 1032:1038 20 mm glucose 1026:1038 20 mm glucose 1026:1038 Here, we aimed at identifying novel signaling pathways involved in the initial release of insulin from PBCs after glucose stimulation using quantitative strategies for the assessment of phosphorylated proteins and sialylated N-linked (SA) glycoproteins.Islets of Langerhans derived from newborn rats with a subsequent 9-10 days of maturation in vitro were stimulated with 20 mm glucose for 0 min (control), 5 min, 10 min, and 15 min. 29113996 2 34 theme insulin 441:447 arg1 secretion 449:457 the insulin secretion 437:457 the insulin secretion 437:457 However, the molecular mechanisms underlying the insulin secretion are unclear. 29113996 4 35 theme phosphorylated 840:853 arg1 proteins 855:862 phosphorylated proteins 840:862 phosphorylated proteins 840:862 Here, we aimed at identifying novel signaling pathways involved in the initial release of insulin from PBCs after glucose stimulation using quantitative strategies for the assessment of phosphorylated proteins and sialylated N-linked (SA) glycoproteins.Islets of Langerhans derived from newborn rats with a subsequent 9-10 days of maturation in vitro were stimulated with 20 mm glucose for 0 min (control), 5 min, 10 min, and 15 min. 29113996 11 36 theme signaling 2286:2294 arg1 pathways 2296:2303 signaling pathways 2286:2303 signaling pathways taking place during brief GSIS of primary PBCs 2286:2350 Collectively, we believe that this comprehensive Proteomics and PTMomics survey of signaling pathways taking place during brief GSIS of primary PBCs is contributing to understanding the complex signaling underlying GSIS. 29113996 4 37 theme quantitative 794:805 arg1 strategies 807:816 quantitative strategies 794:816 quantitative strategies for the assessment of phosphorylated proteins and sialylated N-linked (SA) glycoproteins.Islets of Langerhans derived from newborn rats with a subsequent 9-10 days of maturation in vitro were stimulated with 20 mm glucose for 0 min (control), 5 min, 10 min, and 15 min 794:1085 Here, we aimed at identifying novel signaling pathways involved in the initial release of insulin from PBCs after glucose stimulation using quantitative strategies for the assessment of phosphorylated proteins and sialylated N-linked (SA) glycoproteins.Islets of Langerhans derived from newborn rats with a subsequent 9-10 days of maturation in vitro were stimulated with 20 mm glucose for 0 min (control), 5 min, 10 min, and 15 min. 29113996 11 38 theme comprehensive 2238:2250 arg1 Proteomics 2252:2261 this comprehensive Proteomics and PTMomics survey 2233:2281 Proteomics 2252:2261 Collectively, we believe that this comprehensive Proteomics and PTMomics survey of signaling pathways taking place during brief GSIS of primary PBCs is contributing to understanding the complex signaling underlying GSIS. 29113996 9 39 theme surface 1931:1937 arg1 proteins 1939:1946 several surface proteins 1923:1946 several surface proteins on brief GSIS 1923:1960 Besides protein phosphorylation, alteration in SA glycosylation was observed on several surface proteins on brief GSIS. 29113996 0 40 theme Mechanisms 34:43 arg1 Characterization 0:15 Characterization 0:15 Characterization of the Molecular Mechanisms Underlying Glucose Stimulated Insulin Secretion from Isolated Pancreatic β-cells 0:124 Characterization of the Molecular Mechanisms Underlying Glucose Stimulated Insulin Secretion from Isolated Pancreatic β-cells Using Post-translational Modification Specific Proteomics (PTMomics). 29113996 9 41 from alteration 1876:1885 arg1 glycosylation 1893:1905 SA glycosylation 1890:1905 SA glycosylation 1890:1905 Besides protein phosphorylation, alteration in SA glycosylation was observed on several surface proteins on brief GSIS. 29113996 11 42 theme brief 2325:2329 arg1 GSIS 2331:2334 brief GSIS 2325:2334 brief GSIS of primary PBCs 2325:2350 Collectively, we believe that this comprehensive Proteomics and PTMomics survey of signaling pathways taking place during brief GSIS of primary PBCs is contributing to understanding the complex signaling underlying GSIS. 29113996 4 43 theme glycoproteins.Islets 893:912 arg1 assessment 826:835 the assessment 822:835 the assessment of phosphorylated proteins and sialylated N-linked (SA) glycoproteins.Islets of Langerhans derived from newborn rats with a subsequent 9-10 days of maturation in vitro were stimulated with 20 mm glucose for 0 min (control), 5 min, 10 min, and 15 min 822:1085 Here, we aimed at identifying novel signaling pathways involved in the initial release of insulin from PBCs after glucose stimulation using quantitative strategies for the assessment of phosphorylated proteins and sialylated N-linked (SA) glycoproteins.Islets of Langerhans derived from newborn rats with a subsequent 9-10 days of maturation in vitro were stimulated with 20 mm glucose for 0 min (control), 5 min, 10 min, and 15 min. 29113996 0 44 theme Glucose 56:62 arg1 Secretion 83:91 Glucose Stimulated Insulin Secretion 56:91 Glucose Stimulated Insulin Secretion from Isolated Pancreatic β-cells 56:124 Characterization of the Molecular Mechanisms Underlying Glucose Stimulated Insulin Secretion from Isolated Pancreatic β-cells Using Post-translational Modification Specific Proteomics (PTMomics). 29113996 1 45 theme adequate 332:339 arg1 control 341:347 an adequate control 329:347 an adequate control of energy balance and glucose homeostasis 329:389 Normal pancreatic islet β-cells (PBCs) abundantly secrete insulin in response to elevated blood glucose levels, in order to maintain an adequate control of energy balance and glucose homeostasis. 29113996 3 46 theme insulin 522:528 arg1 GSIS 541:544 GSIS 541:544 GSIS 541:544 Improving our understanding of glucose-stimulated insulin secretion (GSIS) mechanisms under normal conditions is a prerequisite for developing better interventions against diabetes. 29113996 3 46 theme insulin 522:528 arg1 secretion 530:538 glucose-stimulated insulin secretion 503:538 glucose-stimulated insulin secretion (GSIS) mechanisms 503:556 Improving our understanding of glucose-stimulated insulin secretion (GSIS) mechanisms under normal conditions is a prerequisite for developing better interventions against diabetes. 29113996 5 47 theme glycopeptides 1275:1287 arg1 enrichment 1221:1230 enrichment 1221:1230 enrichment of phosphorylated peptides and formerly SA glycopeptides and high-accuracy LC-MS/MS 1221:1314 The isolated islets were subjected to time-resolved quantitative phosphoproteomics and sialiomics using iTRAQ-labeling combined with enrichment of phosphorylated peptides and formerly SA glycopeptides and high-accuracy LC-MS/MS. 29113996 4 48 theme N-linked 879:886 arg1 glycoproteins.Islets 893:912 sialylated N-linked (SA) glycoproteins.Islets 868:912 sialylated N-linked (SA) glycoproteins.Islets of Langerhans derived from newborn rats with a subsequent 9-10 days of maturation in vitro were stimulated with 20 mm glucose for 0 min (control), 5 min, 10 min, and 15 min 868:1085 Here, we aimed at identifying novel signaling pathways involved in the initial release of insulin from PBCs after glucose stimulation using quantitative strategies for the assessment of phosphorylated proteins and sialylated N-linked (SA) glycoproteins.Islets of Langerhans derived from newborn rats with a subsequent 9-10 days of maturation in vitro were stimulated with 20 mm glucose for 0 min (control), 5 min, 10 min, and 15 min. 29113996 1 49 theme islet 214:218 arg1 β-cells 220:226 Normal pancreatic islet β-cells 196:226 Normal pancreatic islet β-cells (PBCs) 196:233 Normal pancreatic islet β-cells (PBCs) abundantly secrete insulin in response to elevated blood glucose levels, in order to maintain an adequate control of energy balance and glucose homeostasis. 29113996 1 49 theme islet 214:218 arg1 PBCs 229:232 PBCs 229:232 PBCs 229:232 Normal pancreatic islet β-cells (PBCs) abundantly secrete insulin in response to elevated blood glucose levels, in order to maintain an adequate control of energy balance and glucose homeostasis. 29113996 5 50 theme high-accuracy 1293:1305 arg1 LC-MS/MS 1307:1314 high-accuracy LC-MS/MS 1293:1314 high-accuracy LC-MS/MS 1293:1314 The isolated islets were subjected to time-resolved quantitative phosphoproteomics and sialiomics using iTRAQ-labeling combined with enrichment of phosphorylated peptides and formerly SA glycopeptides and high-accuracy LC-MS/MS. 29113996 0 51 theme Stimulated 64:73 arg1 Secretion 83:91 Glucose Stimulated Insulin Secretion 56:91 Glucose Stimulated Insulin Secretion from Isolated Pancreatic β-cells 56:124 Characterization of the Molecular Mechanisms Underlying Glucose Stimulated Insulin Secretion from Isolated Pancreatic β-cells Using Post-translational Modification Specific Proteomics (PTMomics). 29113996 10 52 theme protein 2183:2189 arg1 expression 2191:2200 protein expression 2183:2200 protein expression 2183:2200 Interestingly, proteins important for cell-cell interaction, cell movement, cell-ECM interaction and Focal Adhesion (e.g. integrins, semaphorins, and plexins) were found regulated at the level of sialylation, but not in protein expression. 29113996 10 53 theme cell 2024:2027 arg1 movement 2029:2036 cell movement 2024:2036 cell movement 2024:2036 Interestingly, proteins important for cell-cell interaction, cell movement, cell-ECM interaction and Focal Adhesion (e.g. integrins, semaphorins, and plexins) were found regulated at the level of sialylation, but not in protein expression. 29113996 6 54 theme signaling 1365:1373 arg1 pathways 1375:1382 the functional signaling pathways 1350:1382 the functional signaling pathways 1350:1382 Using bioinformatics we analyzed the functional signaling pathways during GSIS, including well-known insulin secretion pathways. 29113996 6 54 theme signaling 1365:1373 arg1 pathways 1436:1443 well-known insulin secretion pathways 1407:1443 well-known insulin secretion pathways 1407:1443 Using bioinformatics we analyzed the functional signaling pathways during GSIS, including well-known insulin secretion pathways. 29113996 1 55 theme elevated 277:284 arg1 levels 300:305 elevated blood glucose levels 277:305 elevated blood glucose levels 277:305 Normal pancreatic islet β-cells (PBCs) abundantly secrete insulin in response to elevated blood glucose levels, in order to maintain an adequate control of energy balance and glucose homeostasis. 29113996 5 56 theme quantitative 1140:1151 arg1 phosphoproteomics 1153:1169 time-resolved quantitative phosphoproteomics 1126:1169 time-resolved quantitative phosphoproteomics 1126:1169 The isolated islets were subjected to time-resolved quantitative phosphoproteomics and sialiomics using iTRAQ-labeling combined with enrichment of phosphorylated peptides and formerly SA glycopeptides and high-accuracy LC-MS/MS. 29113996 7 57 theme 15 1565:1566 arg1 min 1568:1570 min 1568:1570 min 1568:1570 Furthermore, we identified six novel activated signaling pathways (e.g. agrin interactions and prolactin signaling) at 15 min GSIS, which may increase our understanding of the molecular mechanism underlying GSIS. 29113996 4 58 theme newborn 941:947 arg1 rats 949:952 newborn rats 941:952 newborn rats with a subsequent 9-10 days of maturation in vitro were stimulated with 20 mm glucose for 0 min (control), 5 min, 10 min, and 15 min 941:1085 Here, we aimed at identifying novel signaling pathways involved in the initial release of insulin from PBCs after glucose stimulation using quantitative strategies for the assessment of phosphorylated proteins and sialylated N-linked (SA) glycoproteins.Islets of Langerhans derived from newborn rats with a subsequent 9-10 days of maturation in vitro were stimulated with 20 mm glucose for 0 min (control), 5 min, 10 min, and 15 min. 29113996 1 59 theme glucose 292:298 arg1 levels 300:305 elevated blood glucose levels 277:305 elevated blood glucose levels 277:305 Normal pancreatic islet β-cells (PBCs) abundantly secrete insulin in response to elevated blood glucose levels, in order to maintain an adequate control of energy balance and glucose homeostasis. 29113996 6 60 dep analyzed 1341:1348 arg1 Using 1317:1321 Using 1317:1321 Using bioinformatics 1317:1336 Using bioinformatics we analyzed the functional signaling pathways during GSIS, including well-known insulin secretion pathways. 29113996 8 61 theme parallel 1720:1727 arg1 monitoring 1738:1747 parallel reaction monitoring 1720:1747 parallel reaction monitoring 1720:1747 Moreover, we validated some of the regulated phosphosites by parallel reaction monitoring, which resulted in the validation of eleven new phosphosites significantly regulated on GSIS. 29113996 1 62 theme pancreatic 203:212 arg1 β-cells 220:226 Normal pancreatic islet β-cells 196:226 Normal pancreatic islet β-cells (PBCs) 196:233 Normal pancreatic islet β-cells (PBCs) abundantly secrete insulin in response to elevated blood glucose levels, in order to maintain an adequate control of energy balance and glucose homeostasis. 29113996 1 62 theme pancreatic 203:212 arg1 PBCs 229:232 PBCs 229:232 PBCs 229:232 Normal pancreatic islet β-cells (PBCs) abundantly secrete insulin in response to elevated blood glucose levels, in order to maintain an adequate control of energy balance and glucose homeostasis. 29113996 9 63 theme brief 1951:1955 arg1 GSIS 1957:1960 brief GSIS 1951:1960 brief GSIS 1951:1960 Besides protein phosphorylation, alteration in SA glycosylation was observed on several surface proteins on brief GSIS. 29113996 7 64 theme prolactin 1541:1549 arg1 signaling 1551:1559 prolactin signaling 1541:1559 prolactin signaling 1541:1559 Furthermore, we identified six novel activated signaling pathways (e.g. agrin interactions and prolactin signaling) at 15 min GSIS, which may increase our understanding of the molecular mechanism underlying GSIS. 29113996 7 65 theme agrin 1518:1522 arg1 interactions 1524:1535 agrin interactions 1518:1535 agrin interactions 1518:1535 Furthermore, we identified six novel activated signaling pathways (e.g. agrin interactions and prolactin signaling) at 15 min GSIS, which may increase our understanding of the molecular mechanism underlying GSIS. 29113996 3 66 theme better 615:620 arg1 interventions 622:634 better interventions 615:634 better interventions against diabetes 615:651 Improving our understanding of glucose-stimulated insulin secretion (GSIS) mechanisms under normal conditions is a prerequisite for developing better interventions against diabetes. 29113996 8 67 theme phosphosites 1797:1808 arg1 validation 1772:1781 the validation 1768:1781 the validation of eleven new phosphosites significantly regulated on GSIS 1768:1840 Moreover, we validated some of the regulated phosphosites by parallel reaction monitoring, which resulted in the validation of eleven new phosphosites significantly regulated on GSIS. 29113996 11 68 theme signaling 2397:2405 arg1 GSIS 2418:2421 the complex signaling underlying GSIS 2385:2421 the complex signaling underlying GSIS 2385:2421 Collectively, we believe that this comprehensive Proteomics and PTMomics survey of signaling pathways taking place during brief GSIS of primary PBCs is contributing to understanding the complex signaling underlying GSIS. 29113996 6 69 theme secretion 1426:1434 arg1 pathways 1436:1443 well-known insulin secretion pathways 1407:1443 well-known insulin secretion pathways 1407:1443 Using bioinformatics we analyzed the functional signaling pathways during GSIS, including well-known insulin secretion pathways. 29113996 4 70 theme maturation 985:994 arg1 days 977:980 a subsequent 9-10 days 959:980 a subsequent 9-10 days of maturation in vitro 959:1003 Here, we aimed at identifying novel signaling pathways involved in the initial release of insulin from PBCs after glucose stimulation using quantitative strategies for the assessment of phosphorylated proteins and sialylated N-linked (SA) glycoproteins.Islets of Langerhans derived from newborn rats with a subsequent 9-10 days of maturation in vitro were stimulated with 20 mm glucose for 0 min (control), 5 min, 10 min, and 15 min. 29113996 7 71 theme signaling 1493:1501 arg1 pathways 1503:1510 six novel activated signaling pathways 1473:1510 six novel activated signaling pathways (e.g. agrin interactions and prolactin signaling) 1473:1560 Furthermore, we identified six novel activated signaling pathways (e.g. agrin interactions and prolactin signaling) at 15 min GSIS, which may increase our understanding of the molecular mechanism underlying GSIS. 29113996 10 72 theme Focal 2064:2068 arg1 Adhesion 2070:2077 Focal Adhesion 2064:2077 Focal Adhesion (e.g. integrins, semaphorins, and plexins) 2064:2120 Interestingly, proteins important for cell-cell interaction, cell movement, cell-ECM interaction and Focal Adhesion (e.g. integrins, semaphorins, and plexins) were found regulated at the level of sialylation, but not in protein expression. 29113996 6 73 theme well-known 1407:1416 arg1 secretion 1426:1434 well-known insulin secretion 1407:1434 well-known insulin secretion pathways 1407:1443 Using bioinformatics we analyzed the functional signaling pathways during GSIS, including well-known insulin secretion pathways. 29113996 7 74 theme novel 1477:1481 arg1 pathways 1503:1510 six novel activated signaling pathways 1473:1510 six novel activated signaling pathways (e.g. agrin interactions and prolactin signaling) 1473:1560 Furthermore, we identified six novel activated signaling pathways (e.g. agrin interactions and prolactin signaling) at 15 min GSIS, which may increase our understanding of the molecular mechanism underlying GSIS. 29113996 4 75 theme signaling 690:698 arg1 pathways 700:707 novel signaling pathways 684:707 novel signaling pathways involved in the initial release of insulin from PBCs after glucose stimulation using quantitative strategies for the assessment of phosphorylated proteins and sialylated N-linked (SA) glycoproteins.Islets of Langerhans derived from newborn rats with a subsequent 9-10 days of maturation in vitro were stimulated with 20 mm glucose for 0 min (control), 5 min, 10 min, and 15 min 684:1085 Here, we aimed at identifying novel signaling pathways involved in the initial release of insulin from PBCs after glucose stimulation using quantitative strategies for the assessment of phosphorylated proteins and sialylated N-linked (SA) glycoproteins.Islets of Langerhans derived from newborn rats with a subsequent 9-10 days of maturation in vitro were stimulated with 20 mm glucose for 0 min (control), 5 min, 10 min, and 15 min. 29113996 5 76 theme isolated 1092:1099 arg1 islets 1101:1106 The isolated islets 1088:1106 The isolated islets 1088:1106 The isolated islets were subjected to time-resolved quantitative phosphoproteomics and sialiomics using iTRAQ-labeling combined with enrichment of phosphorylated peptides and formerly SA glycopeptides and high-accuracy LC-MS/MS. 29113996 0 77 theme Specific 164:171 arg1 PTMomics 185:192 Post-translational Modification Specific Proteomics (PTMomics) 132:193 Post-translational Modification Specific Proteomics (PTMomics) 132:193 Characterization of the Molecular Mechanisms Underlying Glucose Stimulated Insulin Secretion from Isolated Pancreatic β-cells Using Post-translational Modification Specific Proteomics (PTMomics). 29113996 4 78 from days 977:980 arg1 vitro 999:1003 vitro 999:1003 vitro 999:1003 Here, we aimed at identifying novel signaling pathways involved in the initial release of insulin from PBCs after glucose stimulation using quantitative strategies for the assessment of phosphorylated proteins and sialylated N-linked (SA) glycoproteins.Islets of Langerhans derived from newborn rats with a subsequent 9-10 days of maturation in vitro were stimulated with 20 mm glucose for 0 min (control), 5 min, 10 min, and 15 min. 29113996 7 79 dep interactions 1524:1535 arg1 e.g. 1513:1516 e.g. 1513:1516 e.g. 1513:1516 Furthermore, we identified six novel activated signaling pathways (e.g. agrin interactions and prolactin signaling) at 15 min GSIS, which may increase our understanding of the molecular mechanism underlying GSIS. 29113996 0 80 from β-cells 118:124 arg1 Secretion 83:91 Glucose Stimulated Insulin Secretion 56:91 Glucose Stimulated Insulin Secretion from Isolated Pancreatic β-cells 56:124 Characterization of the Molecular Mechanisms Underlying Glucose Stimulated Insulin Secretion from Isolated Pancreatic β-cells Using Post-translational Modification Specific Proteomics (PTMomics). 29113996 4 81 theme glucose 768:774 arg1 stimulation 776:786 glucose stimulation 768:786 glucose stimulation using quantitative strategies for the assessment of phosphorylated proteins and sialylated N-linked (SA) glycoproteins.Islets of Langerhans derived from newborn rats with a subsequent 9-10 days of maturation in vitro were stimulated with 20 mm glucose for 0 min (control), 5 min, 10 min, and 15 min 768:1085 Here, we aimed at identifying novel signaling pathways involved in the initial release of insulin from PBCs after glucose stimulation using quantitative strategies for the assessment of phosphorylated proteins and sialylated N-linked (SA) glycoproteins.Islets of Langerhans derived from newborn rats with a subsequent 9-10 days of maturation in vitro were stimulated with 20 mm glucose for 0 min (control), 5 min, 10 min, and 15 min. 29113996 9 82 theme protein 1851:1857 arg1 phosphorylation 1859:1873 protein phosphorylation 1851:1873 protein phosphorylation 1851:1873 Besides protein phosphorylation, alteration in SA glycosylation was observed on several surface proteins on brief GSIS. 29113996 0 83 theme Isolated 98:105 arg1 β-cells 118:124 Isolated Pancreatic β-cells 98:124 Isolated Pancreatic β-cells 98:124 Characterization of the Molecular Mechanisms Underlying Glucose Stimulated Insulin Secretion from Isolated Pancreatic β-cells Using Post-translational Modification Specific Proteomics (PTMomics). 29113996 1 84 theme energy 352:357 arg1 balance 359:365 energy balance 352:365 energy balance 352:365 Normal pancreatic islet β-cells (PBCs) abundantly secrete insulin in response to elevated blood glucose levels, in order to maintain an adequate control of energy balance and glucose homeostasis. 29113996 0 85 theme Modification 151:162 arg1 PTMomics 185:192 Post-translational Modification Specific Proteomics (PTMomics) 132:193 Post-translational Modification Specific Proteomics (PTMomics) 132:193 Characterization of the Molecular Mechanisms Underlying Glucose Stimulated Insulin Secretion from Isolated Pancreatic β-cells Using Post-translational Modification Specific Proteomics (PTMomics). 29113996 4 86 theme insulin 744:750 arg1 release 733:739 the initial release 721:739 the initial release of insulin from PBCs after glucose stimulation using quantitative strategies for the assessment of phosphorylated proteins and sialylated N-linked (SA) glycoproteins.Islets of Langerhans derived from newborn rats with a subsequent 9-10 days of maturation in vitro were stimulated with 20 mm glucose for 0 min (control), 5 min, 10 min, and 15 min 721:1085 Here, we aimed at identifying novel signaling pathways involved in the initial release of insulin from PBCs after glucose stimulation using quantitative strategies for the assessment of phosphorylated proteins and sialylated N-linked (SA) glycoproteins.Islets of Langerhans derived from newborn rats with a subsequent 9-10 days of maturation in vitro were stimulated with 20 mm glucose for 0 min (control), 5 min, 10 min, and 15 min. 29113996 7 87 theme mechanism 1632:1640 arg1 understanding 1601:1613 our understanding 1597:1613 our understanding of the molecular mechanism underlying GSIS 1597:1656 Furthermore, we identified six novel activated signaling pathways (e.g. agrin interactions and prolactin signaling) at 15 min GSIS, which may increase our understanding of the molecular mechanism underlying GSIS. 29113996 11 88 theme PBCs 2347:2350 arg1 GSIS 2331:2334 brief GSIS 2325:2334 brief GSIS of primary PBCs 2325:2350 Collectively, we believe that this comprehensive Proteomics and PTMomics survey of signaling pathways taking place during brief GSIS of primary PBCs is contributing to understanding the complex signaling underlying GSIS. 29113996 0 89 theme Post-translational 132:149 arg1 PTMomics 185:192 Post-translational Modification Specific Proteomics (PTMomics) 132:193 Post-translational Modification Specific Proteomics (PTMomics) 132:193 Characterization of the Molecular Mechanisms Underlying Glucose Stimulated Insulin Secretion from Isolated Pancreatic β-cells Using Post-translational Modification Specific Proteomics (PTMomics). 29113996 1 90 theme homeostasis 379:389 arg1 control 341:347 an adequate control 329:347 an adequate control of energy balance and glucose homeostasis 329:389 Normal pancreatic islet β-cells (PBCs) abundantly secrete insulin in response to elevated blood glucose levels, in order to maintain an adequate control of energy balance and glucose homeostasis. 29113996 4 91 theme 20 1026:1027 arg1 mm 1029:1030 mm 1029:1030 mm 1029:1030 Here, we aimed at identifying novel signaling pathways involved in the initial release of insulin from PBCs after glucose stimulation using quantitative strategies for the assessment of phosphorylated proteins and sialylated N-linked (SA) glycoproteins.Islets of Langerhans derived from newborn rats with a subsequent 9-10 days of maturation in vitro were stimulated with 20 mm glucose for 0 min (control), 5 min, 10 min, and 15 min. 29113996 2 92 theme molecular 405:413 arg1 mechanisms 415:424 the molecular mechanisms 401:424 the molecular mechanisms underlying the insulin secretion 401:457 However, the molecular mechanisms underlying the insulin secretion are unclear. 29113996 2 92 theme molecular 405:413 arg1 unclear 463:469 unclear 463:469 unclear 463:469 However, the molecular mechanisms underlying the insulin secretion are unclear. 29113996 11 93 theme PTMomics 2267:2274 arg1 survey 2276:2281 this comprehensive Proteomics and PTMomics survey 2233:2281 survey 2276:2281 Collectively, we believe that this comprehensive Proteomics and PTMomics survey of signaling pathways taking place during brief GSIS of primary PBCs is contributing to understanding the complex signaling underlying GSIS. 29113996 0 94 theme Molecular 24:32 arg1 Mechanisms 34:43 the Molecular Mechanisms 20:43 the Molecular Mechanisms Underlying Glucose Stimulated Insulin Secretion from Isolated Pancreatic β-cells 20:124 Characterization of the Molecular Mechanisms Underlying Glucose Stimulated Insulin Secretion from Isolated Pancreatic β-cells Using Post-translational Modification Specific Proteomics (PTMomics). 29113996 4 95 link N-linked 879:886 arg1 glycoproteins.Islets 893:912 sialylated N-linked (SA) glycoproteins.Islets 868:912 sialylated N-linked (SA) glycoproteins.Islets of Langerhans derived from newborn rats with a subsequent 9-10 days of maturation in vitro were stimulated with 20 mm glucose for 0 min (control), 5 min, 10 min, and 15 min 868:1085 Here, we aimed at identifying novel signaling pathways involved in the initial release of insulin from PBCs after glucose stimulation using quantitative strategies for the assessment of phosphorylated proteins and sialylated N-linked (SA) glycoproteins.Islets of Langerhans derived from newborn rats with a subsequent 9-10 days of maturation in vitro were stimulated with 20 mm glucose for 0 min (control), 5 min, 10 min, and 15 min. 29113996 9 96 theme several 1923:1929 arg1 proteins 1939:1946 several surface proteins 1923:1946 several surface proteins on brief GSIS 1923:1960 Besides protein phosphorylation, alteration in SA glycosylation was observed on several surface proteins on brief GSIS. 29113996 3 97 theme glucose-stimulated 503:520 arg1 GSIS 541:544 GSIS 541:544 GSIS 541:544 Improving our understanding of glucose-stimulated insulin secretion (GSIS) mechanisms under normal conditions is a prerequisite for developing better interventions against diabetes. 29113996 3 97 theme glucose-stimulated 503:520 arg1 secretion 530:538 glucose-stimulated insulin secretion 503:538 glucose-stimulated insulin secretion (GSIS) mechanisms 503:556 Improving our understanding of glucose-stimulated insulin secretion (GSIS) mechanisms under normal conditions is a prerequisite for developing better interventions against diabetes. 29113996 5 98 theme phosphorylated 1235:1248 arg1 peptides 1250:1257 phosphorylated peptides 1235:1257 phosphorylated peptides 1235:1257 The isolated islets were subjected to time-resolved quantitative phosphoproteomics and sialiomics using iTRAQ-labeling combined with enrichment of phosphorylated peptides and formerly SA glycopeptides and high-accuracy LC-MS/MS. 29113996 7 99 theme molecular 1622:1630 arg1 mechanism 1632:1640 the molecular mechanism 1618:1640 the molecular mechanism underlying GSIS 1618:1656 Furthermore, we identified six novel activated signaling pathways (e.g. agrin interactions and prolactin signaling) at 15 min GSIS, which may increase our understanding of the molecular mechanism underlying GSIS. 29113996 9 100 located observed 1911:1918 arg1 proteins 1939:1946 several surface proteins 1923:1946 several surface proteins on brief GSIS 1923:1960 Besides protein phosphorylation, alteration in SA glycosylation was observed on several surface proteins on brief GSIS. 29113996 9 100 located observed 1911:1918 arg2 alteration 1876:1885 alteration 1876:1885 alteration in SA glycosylation 1876:1905 Besides protein phosphorylation, alteration in SA glycosylation was observed on several surface proteins on brief GSIS. 29113996 4 101 from PBCs 757:760 arg1 release 733:739 the initial release 721:739 the initial release of insulin from PBCs after glucose stimulation using quantitative strategies for the assessment of phosphorylated proteins and sialylated N-linked (SA) glycoproteins.Islets of Langerhans derived from newborn rats with a subsequent 9-10 days of maturation in vitro were stimulated with 20 mm glucose for 0 min (control), 5 min, 10 min, and 15 min 721:1085 Here, we aimed at identifying novel signaling pathways involved in the initial release of insulin from PBCs after glucose stimulation using quantitative strategies for the assessment of phosphorylated proteins and sialylated N-linked (SA) glycoproteins.Islets of Langerhans derived from newborn rats with a subsequent 9-10 days of maturation in vitro were stimulated with 20 mm glucose for 0 min (control), 5 min, 10 min, and 15 min. 29113996 11 102 theme pathways 2296:2303 arg1 Proteomics 2252:2261 this comprehensive Proteomics and PTMomics survey 2233:2281 Proteomics 2252:2261 Collectively, we believe that this comprehensive Proteomics and PTMomics survey of signaling pathways taking place during brief GSIS of primary PBCs is contributing to understanding the complex signaling underlying GSIS. 29113996 11 102 theme pathways 2296:2303 arg1 survey 2276:2281 this comprehensive Proteomics and PTMomics survey 2233:2281 survey 2276:2281 Collectively, we believe that this comprehensive Proteomics and PTMomics survey of signaling pathways taking place during brief GSIS of primary PBCs is contributing to understanding the complex signaling underlying GSIS. 29113996 4 103 gly sialylated 868:877 arg1 glycoproteins.Islets 893:912 sialylated N-linked (SA) glycoproteins.Islets 868:912 sialylated N-linked (SA) glycoproteins.Islets of Langerhans derived from newborn rats with a subsequent 9-10 days of maturation in vitro were stimulated with 20 mm glucose for 0 min (control), 5 min, 10 min, and 15 min 868:1085 Here, we aimed at identifying novel signaling pathways involved in the initial release of insulin from PBCs after glucose stimulation using quantitative strategies for the assessment of phosphorylated proteins and sialylated N-linked (SA) glycoproteins.Islets of Langerhans derived from newborn rats with a subsequent 9-10 days of maturation in vitro were stimulated with 20 mm glucose for 0 min (control), 5 min, 10 min, and 15 min. 29113996 4 104 dep N-linked 879:886 arg1 SA 889:890 SA 889:890 SA 889:890 Here, we aimed at identifying novel signaling pathways involved in the initial release of insulin from PBCs after glucose stimulation using quantitative strategies for the assessment of phosphorylated proteins and sialylated N-linked (SA) glycoproteins.Islets of Langerhans derived from newborn rats with a subsequent 9-10 days of maturation in vitro were stimulated with 20 mm glucose for 0 min (control), 5 min, 10 min, and 15 min. 29113996 10 105 theme cell-cell 2001:2009 arg1 interaction 2011:2021 cell-cell interaction 2001:2021 cell-cell interaction 2001:2021 Interestingly, proteins important for cell-cell interaction, cell movement, cell-ECM interaction and Focal Adhesion (e.g. integrins, semaphorins, and plexins) were found regulated at the level of sialylation, but not in protein expression. 29113996 10 106 theme sialylation 2159:2169 arg1 level 2150:2154 the level 2146:2154 the level of sialylation 2146:2169 Interestingly, proteins important for cell-cell interaction, cell movement, cell-ECM interaction and Focal Adhesion (e.g. integrins, semaphorins, and plexins) were found regulated at the level of sialylation, but not in protein expression. 29113996 10 107 theme important 1987:1995 arg1 proteins 1978:1985 proteins 1978:1985 proteins important for cell-cell interaction, cell movement, cell-ECM interaction and Focal Adhesion (e.g. integrins, semaphorins, and plexins) 1978:2120 Interestingly, proteins important for cell-cell interaction, cell movement, cell-ECM interaction and Focal Adhesion (e.g. integrins, semaphorins, and plexins) were found regulated at the level of sialylation, but not in protein expression. 29113996 4 108 theme proteins 855:862 arg1 assessment 826:835 the assessment 822:835 the assessment of phosphorylated proteins and sialylated N-linked (SA) glycoproteins.Islets of Langerhans derived from newborn rats with a subsequent 9-10 days of maturation in vitro were stimulated with 20 mm glucose for 0 min (control), 5 min, 10 min, and 15 min 822:1085 Here, we aimed at identifying novel signaling pathways involved in the initial release of insulin from PBCs after glucose stimulation using quantitative strategies for the assessment of phosphorylated proteins and sialylated N-linked (SA) glycoproteins.Islets of Langerhans derived from newborn rats with a subsequent 9-10 days of maturation in vitro were stimulated with 20 mm glucose for 0 min (control), 5 min, 10 min, and 15 min. 29113996 3 109 theme secretion 530:538 arg1 mechanisms 547:556 glucose-stimulated insulin secretion (GSIS) mechanisms 503:556 glucose-stimulated insulin secretion (GSIS) mechanisms 503:556 Improving our understanding of glucose-stimulated insulin secretion (GSIS) mechanisms under normal conditions is a prerequisite for developing better interventions against diabetes. 29113996 8 110 theme regulated 1694:1702 arg1 phosphosites 1704:1715 the regulated phosphosites 1690:1715 the regulated phosphosites 1690:1715 Moreover, we validated some of the regulated phosphosites by parallel reaction monitoring, which resulted in the validation of eleven new phosphosites significantly regulated on GSIS. 29113996 4 111 theme sialylated 868:877 arg1 glycoproteins.Islets 893:912 sialylated N-linked (SA) glycoproteins.Islets 868:912 sialylated N-linked (SA) glycoproteins.Islets of Langerhans derived from newborn rats with a subsequent 9-10 days of maturation in vitro were stimulated with 20 mm glucose for 0 min (control), 5 min, 10 min, and 15 min 868:1085 Here, we aimed at identifying novel signaling pathways involved in the initial release of insulin from PBCs after glucose stimulation using quantitative strategies for the assessment of phosphorylated proteins and sialylated N-linked (SA) glycoproteins.Islets of Langerhans derived from newborn rats with a subsequent 9-10 days of maturation in vitro were stimulated with 20 mm glucose for 0 min (control), 5 min, 10 min, and 15 min. 29113996 3 112 theme normal 564:569 arg1 conditions 571:580 normal conditions 564:580 normal conditions 564:580 Improving our understanding of glucose-stimulated insulin secretion (GSIS) mechanisms under normal conditions is a prerequisite for developing better interventions against diabetes. 29113996 5 113 theme LC-MS/MS 1307:1314 arg1 enrichment 1221:1230 enrichment 1221:1230 enrichment of phosphorylated peptides and formerly SA glycopeptides and high-accuracy LC-MS/MS 1221:1314 The isolated islets were subjected to time-resolved quantitative phosphoproteomics and sialiomics using iTRAQ-labeling combined with enrichment of phosphorylated peptides and formerly SA glycopeptides and high-accuracy LC-MS/MS. 28844706 12 0 theme step-by-step 2169:2180 arg1 instruction 2182:2192 the step-by-step instruction 2165:2192 the step-by-step instruction 2165:2192 On the top the step-by-step instruction how to use the application, the paper includes a worked example demonstrates the way glycan structure elucidation of human immunoglobulin G is processed with the help of the simple and rapid GU value calculation of this new application. 28844706 13 1 theme analysis 2576:2583 arg1 glycomics 2515:2523 cutting-edge glycomics 2502:2523 cutting-edge glycomics of exploratory research or high-throughput routine analysis 2502:2583 After very short training period, the software can be used readily for cutting-edge glycomics of exploratory research or high-throughput routine analysis. 28844706 6 2 theme immunoglobulin 1164:1177 arg1 G 1179:1179 human immunoglobulin G 1158:1179 human immunoglobulin G 1158:1179 Furthermore, a worked example demonstrates the way glycan structural elucidation of human immunoglobulin G is processed with the help of this simple and rapid GU value calculation application. 28844706 2 3 theme induced 362:368 arg1 CE-LIF 393:398 CE-LIF 393:398 CE-LIF 393:398 One of the frequently used methods for the analysis of complex carbohydrates is capillary electrophoresis with laser induced fluorescent detection (CE-LIF). 28844706 2 3 theme induced 362:368 arg1 detection 382:390 laser induced fluorescent detection 356:390 laser induced fluorescent detection (CE-LIF) 356:399 One of the frequently used methods for the analysis of complex carbohydrates is capillary electrophoresis with laser induced fluorescent detection (CE-LIF). 28844706 7 4 from development 1333:1343 arg1 years 1355:1359 recent years 1348:1359 recent years 1348:1359 SIGNIFICANCE Biopharmaceuticals have seen something of tremendous development in recent years, which governs the parallel blooming of analytical glycomics. 28844706 6 5 theme calculation 1242:1252 arg1 application 1254:1264 this simple and rapid GU value calculation application 1211:1264 this simple and rapid GU value calculation application 1211:1264 Furthermore, a worked example demonstrates the way glycan structural elucidation of human immunoglobulin G is processed with the help of this simple and rapid GU value calculation application. 28844706 7 6 theme tremendous 1322:1331 arg1 development 1333:1343 tremendous development 1322:1343 tremendous development in recent years 1322:1359 SIGNIFICANCE Biopharmaceuticals have seen something of tremendous development in recent years, which governs the parallel blooming of analytical glycomics. 28844706 6 7 theme GU 1233:1234 arg1 application 1254:1264 this simple and rapid GU value calculation application 1211:1264 this simple and rapid GU value calculation application 1211:1264 Furthermore, a worked example demonstrates the way glycan structural elucidation of human immunoglobulin G is processed with the help of this simple and rapid GU value calculation application. 28844706 7 8 theme analytical 1401:1410 arg1 glycomics 1412:1420 analytical glycomics 1401:1420 analytical glycomics 1401:1420 SIGNIFICANCE Biopharmaceuticals have seen something of tremendous development in recent years, which governs the parallel blooming of analytical glycomics. 28844706 2 9 theme methods 272:278 arg1 methods 272:278 the frequently used methods 252:278 the frequently used methods for the analysis of complex carbohydrates 252:320 One of the frequently used methods for the analysis of complex carbohydrates is capillary electrophoresis with laser induced fluorescent detection (CE-LIF). 28844706 2 9 theme methods 272:278 arg1 One 245:247 One 245:247 One 245:247 One of the frequently used methods for the analysis of complex carbohydrates is capillary electrophoresis with laser induced fluorescent detection (CE-LIF). 28844706 11 10 theme GUcal 1943:1947 arg1 application 1949:1959 the recently disseminated GUcal application 1917:1959 the recently disseminated GUcal application 1917:1959 According to our best knowledge, this is the first tutorial paper on the recently disseminated GUcal application, which automatically calculates GU values for all sample components of interest in an electropherogram using either the bracketing standard approach or the new triple internal standard method. 28844706 12 11 theme way 2275:2277 arg1 structure 2286:2294 the way glycan structure 2271:2294 the way glycan structure elucidation of human immunoglobulin G is processed with the help of the simple and rapid GU value calculation of this new application 2271:2428 On the top the step-by-step instruction how to use the application, the paper includes a worked example demonstrates the way glycan structure elucidation of human immunoglobulin G is processed with the help of the simple and rapid GU value calculation of this new application. 28844706 1 12 gly glycoproteins 197:209 arg1 glycoproteins 197:209 glycoproteins 197:209 glycoproteins introduced as biopharmaceuticals 197:242 In recent years, analytical glycomics gained a significant role due to the rapidly increasing number of glycoproteins introduced as biopharmaceuticals. 28844706 2 13 theme carbohydrates 308:320 arg1 analysis 288:295 the analysis 284:295 the analysis of complex carbohydrates 284:320 One of the frequently used methods for the analysis of complex carbohydrates is capillary electrophoresis with laser induced fluorescent detection (CE-LIF). 28844706 1 14 theme increasing 176:185 arg1 number 187:192 the rapidly increasing number 164:192 the rapidly increasing number of glycoproteins introduced as biopharmaceuticals 164:242 In recent years, analytical glycomics gained a significant role due to the rapidly increasing number of glycoproteins introduced as biopharmaceuticals. 28844706 4 15 theme glucose 696:702 arg1 unit 704:707 their glucose unit 690:707 their glucose unit (GU) values 690:719 Individual glycan structures corresponding to the separated peaks in an electropherogram are identified according to their glucose unit (GU) values by mining the built in database. 28844706 4 15 theme glucose 696:702 arg1 GU 710:711 GU 710:711 GU 710:711 Individual glycan structures corresponding to the separated peaks in an electropherogram are identified according to their glucose unit (GU) values by mining the built in database. 28844706 13 16 theme exploratory 2528:2538 arg1 research 2540:2547 exploratory research 2528:2547 exploratory research 2528:2547 After very short training period, the software can be used readily for cutting-edge glycomics of exploratory research or high-throughput routine analysis. 28844706 6 17 theme human 1158:1162 arg1 G 1179:1179 human immunoglobulin G 1158:1179 human immunoglobulin G 1158:1179 Furthermore, a worked example demonstrates the way glycan structural elucidation of human immunoglobulin G is processed with the help of this simple and rapid GU value calculation application. 28844706 12 18 dep the 2352:2354 arg1 help 2356:2359 help 2356:2359 help 2356:2359 On the top the step-by-step instruction how to use the application, the paper includes a worked example demonstrates the way glycan structure elucidation of human immunoglobulin G is processed with the help of the simple and rapid GU value calculation of this new application. 28844706 8 19 theme induced 1540:1546 arg1 detection 1560:1568 laser induced fluorescent detection 1534:1568 laser induced fluorescent detection (CE-LIF) 1534:1577 One of the frequently used methods for the analysis of complex carbohydrates is capillary electrophoresis with laser induced fluorescent detection (CE-LIF). 28844706 8 19 theme induced 1540:1546 arg1 CE-LIF 1571:1576 CE-LIF 1571:1576 CE-LIF 1571:1576 One of the frequently used methods for the analysis of complex carbohydrates is capillary electrophoresis with laser induced fluorescent detection (CE-LIF). 28844706 6 20 theme glycan 1125:1130 arg1 elucidation 1143:1153 glycan structural elucidation 1125:1153 glycan structural elucidation of human immunoglobulin G 1125:1179 Furthermore, a worked example demonstrates the way glycan structural elucidation of human immunoglobulin G is processed with the help of this simple and rapid GU value calculation application. 28844706 12 21 theme worked 2243:2248 arg1 example 2250:2256 a worked example 2241:2256 a worked example demonstrates the way glycan structure elucidation of human immunoglobulin G is processed with the help of the simple and rapid GU value calculation of this new application 2241:2428 On the top the step-by-step instruction how to use the application, the paper includes a worked example demonstrates the way glycan structure elucidation of human immunoglobulin G is processed with the help of the simple and rapid GU value calculation of this new application. 28844706 10 22 theme CE 1757:1758 arg1 instrumentation 1760:1774 CE instrumentation 1757:1774 CE instrumentation 1757:1774 While CE instrumentation is well developed, the related bioinformatics tools are lagging behind. 28844706 13 23 theme short 2442:2446 arg1 period 2457:2462 very short training period 2437:2462 very short training period 2437:2462 After very short training period, the software can be used readily for cutting-edge glycomics of exploratory research or high-throughput routine analysis. 28844706 8 24 with electrophoresis 1513:1527 arg1 detection 1560:1568 laser induced fluorescent detection 1534:1568 laser induced fluorescent detection (CE-LIF) 1534:1577 One of the frequently used methods for the analysis of complex carbohydrates is capillary electrophoresis with laser induced fluorescent detection (CE-LIF). 28844706 8 24 with electrophoresis 1513:1527 arg1 CE-LIF 1571:1576 CE-LIF 1571:1576 CE-LIF 1571:1576 One of the frequently used methods for the analysis of complex carbohydrates is capillary electrophoresis with laser induced fluorescent detection (CE-LIF). 28844706 3 25 with technique 441:449 arg1 sensitivity 466:476 excellent sensitivity 456:476 excellent sensitivity capable of discriminating between closely related positional and linkage carbohydrate isomers 456:570 CE-LIF is a high resolution separation technique with excellent sensitivity capable of discriminating between closely related positional and linkage carbohydrate isomers. 28844706 11 26 theme standard 2092:2099 arg1 approach 2101:2108 the bracketing standard approach 2077:2108 the bracketing standard approach 2077:2108 According to our best knowledge, this is the first tutorial paper on the recently disseminated GUcal application, which automatically calculates GU values for all sample components of interest in an electropherogram using either the bracketing standard approach or the new triple internal standard method. 28844706 1 27 theme analytical 110:119 arg1 glycomics 121:129 analytical glycomics 110:129 analytical glycomics 110:129 In recent years, analytical glycomics gained a significant role due to the rapidly increasing number of glycoproteins introduced as biopharmaceuticals. 28844706 11 28 theme triple 2121:2126 arg1 method 2146:2151 the new triple internal standard method 2113:2151 the new triple internal standard method 2113:2151 According to our best knowledge, this is the first tutorial paper on the recently disseminated GUcal application, which automatically calculates GU values for all sample components of interest in an electropherogram using either the bracketing standard approach or the new triple internal standard method. 28844706 13 29 theme research 2540:2547 arg1 glycomics 2515:2523 cutting-edge glycomics 2502:2523 cutting-edge glycomics of exploratory research or high-throughput routine analysis 2502:2583 After very short training period, the software can be used readily for cutting-edge glycomics of exploratory research or high-throughput routine analysis. 28844706 11 30 theme internal 2128:2135 arg1 method 2146:2151 the new triple internal standard method 2113:2151 the new triple internal standard method 2113:2151 According to our best knowledge, this is the first tutorial paper on the recently disseminated GUcal application, which automatically calculates GU values for all sample components of interest in an electropherogram using either the bracketing standard approach or the new triple internal standard method. 28844706 9 31 theme resolution 1597:1606 arg1 technique 1619:1627 a high resolution separation technique 1590:1627 a high resolution separation technique with excellent sensitivity capable of discriminating between closely related positional and linkage carbohydrate isomers 1590:1748 CE-LIF is a high resolution separation technique with excellent sensitivity capable of discriminating between closely related positional and linkage carbohydrate isomers. 28844706 9 31 theme resolution 1597:1606 arg1 CE-LIF 1580:1585 CE-LIF 1580:1585 CE-LIF 1580:1585 CE-LIF is a high resolution separation technique with excellent sensitivity capable of discriminating between closely related positional and linkage carbohydrate isomers. 28844706 11 32 theme new 2117:2119 arg1 method 2146:2151 the new triple internal standard method 2113:2151 the new triple internal standard method 2113:2151 According to our best knowledge, this is the first tutorial paper on the recently disseminated GUcal application, which automatically calculates GU values for all sample components of interest in an electropherogram using either the bracketing standard approach or the new triple internal standard method. 28844706 5 33 theme interest 937:944 arg1 components 923:932 all sample components 912:932 all sample components of interest 912:944 This tutorial introduces the practical use of the GUcal application, a recently developed glycoinformatics tool, which automatically calculates GU values for all sample components of interest in an electropherogram using either the bracketing standard approach or the recently published triple internal standard method. 28844706 11 34 theme tutorial 1899:1906 arg1 this 1881:1884 this 1881:1884 this 1881:1884 According to our best knowledge, this is the first tutorial paper on the recently disseminated GUcal application, which automatically calculates GU values for all sample components of interest in an electropherogram using either the bracketing standard approach or the new triple internal standard method. 28844706 11 34 theme tutorial 1899:1906 arg1 paper 1908:1912 the first tutorial paper 1889:1912 the first tutorial paper on the recently disseminated GUcal application, which automatically calculates GU values for all sample components of interest in an electropherogram using either the bracketing standard approach or the new triple internal standard method 1889:2151 According to our best knowledge, this is the first tutorial paper on the recently disseminated GUcal application, which automatically calculates GU values for all sample components of interest in an electropherogram using either the bracketing standard approach or the new triple internal standard method. 28844706 5 35 theme application 810:820 arg1 use 793:795 the practical use 779:795 the practical use of the GUcal application, a recently developed glycoinformatics tool, which automatically calculates GU values for all sample components of interest in an electropherogram using either the bracketing standard approach or the recently published triple internal standard method 779:1071 This tutorial introduces the practical use of the GUcal application, a recently developed glycoinformatics tool, which automatically calculates GU values for all sample components of interest in an electropherogram using either the bracketing standard approach or the recently published triple internal standard method. 28844706 1 36 theme due 157:159 arg1 role 152:155 a significant role 138:155 a significant role due to the rapidly increasing number of glycoproteins introduced as biopharmaceuticals 138:242 In recent years, analytical glycomics gained a significant role due to the rapidly increasing number of glycoproteins introduced as biopharmaceuticals. 28844706 12 37 theme new 2414:2416 arg1 application 2418:2428 this new application 2409:2428 this new application 2409:2428 On the top the step-by-step instruction how to use the application, the paper includes a worked example demonstrates the way glycan structure elucidation of human immunoglobulin G is processed with the help of the simple and rapid GU value calculation of this new application. 28844706 9 38 theme capable 1656:1662 arg1 sensitivity 1644:1654 excellent sensitivity 1634:1654 excellent sensitivity capable of discriminating between closely related positional and linkage carbohydrate isomers 1634:1748 CE-LIF is a high resolution separation technique with excellent sensitivity capable of discriminating between closely related positional and linkage carbohydrate isomers. 28844706 13 39 used used 2485:2488 arg2 software 2469:2476 the software 2465:2476 the software 2465:2476 After very short training period, the software can be used readily for cutting-edge glycomics of exploratory research or high-throughput routine analysis. 28844706 12 40 theme rapid 2379:2383 arg1 calculation 2394:2404 the simple and rapid GU value calculation 2364:2404 the simple and rapid GU value calculation of this new application 2364:2428 On the top the step-by-step instruction how to use the application, the paper includes a worked example demonstrates the way glycan structure elucidation of human immunoglobulin G is processed with the help of the simple and rapid GU value calculation of this new application. 28844706 6 41 dep way 1121:1123 arg1 processed 1184:1192 processed 1184:1192 is processed with the help of this simple and rapid GU value calculation application 1181:1264 Furthermore, a worked example demonstrates the way glycan structural elucidation of human immunoglobulin G is processed with the help of this simple and rapid GU value calculation application. 28844706 4 42 from peaks 633:637 arg1 electropherogram 645:660 an electropherogram 642:660 an electropherogram 642:660 Individual glycan structures corresponding to the separated peaks in an electropherogram are identified according to their glucose unit (GU) values by mining the built in database. 28844706 5 43 theme triple 1041:1046 arg1 method 1066:1071 the recently published triple internal standard method 1018:1071 the recently published triple internal standard method 1018:1071 This tutorial introduces the practical use of the GUcal application, a recently developed glycoinformatics tool, which automatically calculates GU values for all sample components of interest in an electropherogram using either the bracketing standard approach or the recently published triple internal standard method. 28844706 12 44 theme value 2388:2392 arg1 calculation 2394:2404 the simple and rapid GU value calculation 2364:2404 the simple and rapid GU value calculation of this new application 2364:2428 On the top the step-by-step instruction how to use the application, the paper includes a worked example demonstrates the way glycan structure elucidation of human immunoglobulin G is processed with the help of the simple and rapid GU value calculation of this new application. 28844706 3 45 theme separation 430:439 arg1 CE-LIF 402:407 CE-LIF 402:407 CE-LIF 402:407 CE-LIF is a high resolution separation technique with excellent sensitivity capable of discriminating between closely related positional and linkage carbohydrate isomers. 28844706 3 45 theme separation 430:439 arg1 technique 441:449 a high resolution separation technique 412:449 a high resolution separation technique with excellent sensitivity capable of discriminating between closely related positional and linkage carbohydrate isomers 412:570 CE-LIF is a high resolution separation technique with excellent sensitivity capable of discriminating between closely related positional and linkage carbohydrate isomers. 28844706 0 46 theme Structural 0:9 arg1 identification 11:24 Structural identification 0:24 Structural identification of N-linked carbohydrates using the GUcal application: A tutorial. 0:91 Structural identification of N-linked carbohydrates using the GUcal application: A tutorial. 28844706 5 47 theme standard 997:1004 arg1 approach 1006:1013 the bracketing standard approach 982:1013 the bracketing standard approach 982:1013 This tutorial introduces the practical use of the GUcal application, a recently developed glycoinformatics tool, which automatically calculates GU values for all sample components of interest in an electropherogram using either the bracketing standard approach or the recently published triple internal standard method. 28844706 7 48 theme glycomics 1412:1420 arg1 blooming 1389:1396 the parallel blooming 1376:1396 the parallel blooming of analytical glycomics 1376:1420 SIGNIFICANCE Biopharmaceuticals have seen something of tremendous development in recent years, which governs the parallel blooming of analytical glycomics. 28844706 12 49 theme immunoglobulin 2317:2330 arg1 G 2332:2332 human immunoglobulin G 2311:2332 human immunoglobulin G 2311:2332 On the top the step-by-step instruction how to use the application, the paper includes a worked example demonstrates the way glycan structure elucidation of human immunoglobulin G is processed with the help of the simple and rapid GU value calculation of this new application. 28844706 2 50 with electrophoresis 335:349 arg1 CE-LIF 393:398 CE-LIF 393:398 CE-LIF 393:398 One of the frequently used methods for the analysis of complex carbohydrates is capillary electrophoresis with laser induced fluorescent detection (CE-LIF). 28844706 2 50 with electrophoresis 335:349 arg1 detection 382:390 laser induced fluorescent detection 356:390 laser induced fluorescent detection (CE-LIF) 356:399 One of the frequently used methods for the analysis of complex carbohydrates is capillary electrophoresis with laser induced fluorescent detection (CE-LIF). 28844706 3 51 theme high 414:417 arg1 CE-LIF 402:407 CE-LIF 402:407 CE-LIF 402:407 CE-LIF is a high resolution separation technique with excellent sensitivity capable of discriminating between closely related positional and linkage carbohydrate isomers. 28844706 3 51 theme high 414:417 arg1 technique 441:449 a high resolution separation technique 412:449 a high resolution separation technique with excellent sensitivity capable of discriminating between closely related positional and linkage carbohydrate isomers 412:570 CE-LIF is a high resolution separation technique with excellent sensitivity capable of discriminating between closely related positional and linkage carbohydrate isomers. 28844706 8 52 theme complex 1478:1484 arg1 carbohydrates 1486:1498 complex carbohydrates 1478:1498 complex carbohydrates 1478:1498 One of the frequently used methods for the analysis of complex carbohydrates is capillary electrophoresis with laser induced fluorescent detection (CE-LIF). 28844706 10 53 theme related 1799:1805 arg1 tools 1822:1826 the related bioinformatics tools 1795:1826 the related bioinformatics tools 1795:1826 While CE instrumentation is well developed, the related bioinformatics tools are lagging behind. 28844706 0 54 theme carbohydrates 38:50 arg1 identification 11:24 Structural identification 0:24 Structural identification of N-linked carbohydrates using the GUcal application: A tutorial. 0:91 Structural identification of N-linked carbohydrates using the GUcal application: A tutorial. 28844706 7 55 theme parallel 1380:1387 arg1 blooming 1389:1396 the parallel blooming 1376:1396 the parallel blooming of analytical glycomics 1376:1420 SIGNIFICANCE Biopharmaceuticals have seen something of tremendous development in recent years, which governs the parallel blooming of analytical glycomics. 28844706 2 56 theme laser 356:360 arg1 CE-LIF 393:398 CE-LIF 393:398 CE-LIF 393:398 One of the frequently used methods for the analysis of complex carbohydrates is capillary electrophoresis with laser induced fluorescent detection (CE-LIF). 28844706 2 56 theme laser 356:360 arg1 detection 382:390 laser induced fluorescent detection 356:390 laser induced fluorescent detection (CE-LIF) 356:399 One of the frequently used methods for the analysis of complex carbohydrates is capillary electrophoresis with laser induced fluorescent detection (CE-LIF). 28844706 5 57 theme developed 834:842 arg1 tool 861:864 a recently developed glycoinformatics tool 823:864 a recently developed glycoinformatics tool 823:864 This tutorial introduces the practical use of the GUcal application, a recently developed glycoinformatics tool, which automatically calculates GU values for all sample components of interest in an electropherogram using either the bracketing standard approach or the recently published triple internal standard method. 28844706 5 57 theme developed 834:842 arg1 application 810:820 the GUcal application 800:820 the GUcal application 800:820 This tutorial introduces the practical use of the GUcal application, a recently developed glycoinformatics tool, which automatically calculates GU values for all sample components of interest in an electropherogram using either the bracketing standard approach or the recently published triple internal standard method. 28844706 4 58 theme glycan 584:589 arg1 structures 591:600 Individual glycan structures 573:600 Individual glycan structures corresponding to the separated peaks in an electropherogram 573:660 Individual glycan structures corresponding to the separated peaks in an electropherogram are identified according to their glucose unit (GU) values by mining the built in database. 28844706 11 59 theme best 1865:1868 arg1 knowledge 1870:1878 our best knowledge 1861:1878 our best knowledge 1861:1878 According to our best knowledge, this is the first tutorial paper on the recently disseminated GUcal application, which automatically calculates GU values for all sample components of interest in an electropherogram using either the bracketing standard approach or the new triple internal standard method. 28844706 5 60 theme standard 1057:1064 arg1 method 1066:1071 the recently published triple internal standard method 1018:1071 the recently published triple internal standard method 1018:1071 This tutorial introduces the practical use of the GUcal application, a recently developed glycoinformatics tool, which automatically calculates GU values for all sample components of interest in an electropherogram using either the bracketing standard approach or the recently published triple internal standard method. 28844706 1 61 theme significant 140:150 arg1 role 152:155 a significant role 138:155 a significant role due to the rapidly increasing number of glycoproteins introduced as biopharmaceuticals 138:242 In recent years, analytical glycomics gained a significant role due to the rapidly increasing number of glycoproteins introduced as biopharmaceuticals. 28844706 8 62 theme laser 1534:1538 arg1 detection 1560:1568 laser induced fluorescent detection 1534:1568 laser induced fluorescent detection (CE-LIF) 1534:1577 One of the frequently used methods for the analysis of complex carbohydrates is capillary electrophoresis with laser induced fluorescent detection (CE-LIF). 28844706 8 62 theme laser 1534:1538 arg1 CE-LIF 1571:1576 CE-LIF 1571:1576 CE-LIF 1571:1576 One of the frequently used methods for the analysis of complex carbohydrates is capillary electrophoresis with laser induced fluorescent detection (CE-LIF). 28844706 3 63 theme carbohydrate 551:562 arg1 isomers 564:570 carbohydrate isomers 551:570 carbohydrate isomers 551:570 CE-LIF is a high resolution separation technique with excellent sensitivity capable of discriminating between closely related positional and linkage carbohydrate isomers. 28844706 12 64 dep example 2250:2256 arg1 demonstrates 2258:2269 demonstrates 2258:2269 demonstrates the way glycan structure elucidation of human immunoglobulin G is processed with the help of the simple and rapid GU value calculation of this new application 2258:2428 On the top the step-by-step instruction how to use the application, the paper includes a worked example demonstrates the way glycan structure elucidation of human immunoglobulin G is processed with the help of the simple and rapid GU value calculation of this new application. 28844706 7 65 theme recent 1348:1353 arg1 years 1355:1359 recent years 1348:1359 recent years 1348:1359 SIGNIFICANCE Biopharmaceuticals have seen something of tremendous development in recent years, which governs the parallel blooming of analytical glycomics. 28844706 2 66 theme fluorescent 370:380 arg1 CE-LIF 393:398 CE-LIF 393:398 CE-LIF 393:398 One of the frequently used methods for the analysis of complex carbohydrates is capillary electrophoresis with laser induced fluorescent detection (CE-LIF). 28844706 2 66 theme fluorescent 370:380 arg1 detection 382:390 laser induced fluorescent detection 356:390 laser induced fluorescent detection (CE-LIF) 356:399 One of the frequently used methods for the analysis of complex carbohydrates is capillary electrophoresis with laser induced fluorescent detection (CE-LIF). 28844706 4 67 from built 735:739 arg1 database 744:751 database 744:751 database 744:751 Individual glycan structures corresponding to the separated peaks in an electropherogram are identified according to their glucose unit (GU) values by mining the built in database. 28844706 0 68 link N-linked 29:36 arg1 carbohydrates 38:50 N-linked carbohydrates 29:50 N-linked carbohydrates using the GUcal application 29:78 Structural identification of N-linked carbohydrates using the GUcal application: A tutorial. 28844706 7 69 theme development 1333:1343 arg1 something 1309:1317 something 1309:1317 something 1309:1317 SIGNIFICANCE Biopharmaceuticals have seen something of tremendous development in recent years, which governs the parallel blooming of analytical glycomics. 28844706 13 70 theme cutting-edge 2502:2513 arg1 glycomics 2515:2523 cutting-edge glycomics 2502:2523 cutting-edge glycomics of exploratory research or high-throughput routine analysis 2502:2583 After very short training period, the software can be used readily for cutting-edge glycomics of exploratory research or high-throughput routine analysis. 28844706 6 71 theme value 1236:1240 arg1 application 1254:1264 this simple and rapid GU value calculation application 1211:1264 this simple and rapid GU value calculation application 1211:1264 Furthermore, a worked example demonstrates the way glycan structural elucidation of human immunoglobulin G is processed with the help of this simple and rapid GU value calculation application. 28844706 11 72 theme GU 1993:1994 arg1 values 1996:2001 GU values 1993:2001 GU values for all sample components of interest 1993:2039 According to our best knowledge, this is the first tutorial paper on the recently disseminated GUcal application, which automatically calculates GU values for all sample components of interest in an electropherogram using either the bracketing standard approach or the new triple internal standard method. 28844706 11 73 theme standard 2137:2144 arg1 method 2146:2151 the new triple internal standard method 2113:2151 the new triple internal standard method 2113:2151 According to our best knowledge, this is the first tutorial paper on the recently disseminated GUcal application, which automatically calculates GU values for all sample components of interest in an electropherogram using either the bracketing standard approach or the new triple internal standard method. 28844706 12 74 dep structure 2286:2294 arg1 processed 2337:2345 processed 2337:2345 is processed with the help of the simple and rapid GU value calculation of this new application 2334:2428 On the top the step-by-step instruction how to use the application, the paper includes a worked example demonstrates the way glycan structure elucidation of human immunoglobulin G is processed with the help of the simple and rapid GU value calculation of this new application. 28844706 13 75 theme training 2448:2455 arg1 period 2457:2462 very short training period 2437:2462 very short training period 2437:2462 After very short training period, the software can be used readily for cutting-edge glycomics of exploratory research or high-throughput routine analysis. 28844706 7 76 from years 1355:1359 arg1 something 1309:1317 something 1309:1317 something 1309:1317 SIGNIFICANCE Biopharmaceuticals have seen something of tremendous development in recent years, which governs the parallel blooming of analytical glycomics. 28844706 6 77 theme rapid 1227:1231 arg1 application 1254:1264 this simple and rapid GU value calculation application 1211:1264 this simple and rapid GU value calculation application 1211:1264 Furthermore, a worked example demonstrates the way glycan structural elucidation of human immunoglobulin G is processed with the help of this simple and rapid GU value calculation application. 28844706 5 78 theme sample 916:921 arg1 components 923:932 all sample components 912:932 all sample components of interest 912:944 This tutorial introduces the practical use of the GUcal application, a recently developed glycoinformatics tool, which automatically calculates GU values for all sample components of interest in an electropherogram using either the bracketing standard approach or the recently published triple internal standard method. 28844706 6 79 theme simple 1216:1221 arg1 application 1254:1264 this simple and rapid GU value calculation application 1211:1264 this simple and rapid GU value calculation application 1211:1264 Furthermore, a worked example demonstrates the way glycan structural elucidation of human immunoglobulin G is processed with the help of this simple and rapid GU value calculation application. 28844706 11 80 theme disseminated 1930:1941 arg1 application 1949:1959 the recently disseminated GUcal application 1917:1959 the recently disseminated GUcal application 1917:1959 According to our best knowledge, this is the first tutorial paper on the recently disseminated GUcal application, which automatically calculates GU values for all sample components of interest in an electropherogram using either the bracketing standard approach or the new triple internal standard method. 28844706 12 81 theme G 2332:2332 arg1 elucidation 2296:2306 elucidation 2296:2306 elucidation of human immunoglobulin G 2296:2332 On the top the step-by-step instruction how to use the application, the paper includes a worked example demonstrates the way glycan structure elucidation of human immunoglobulin G is processed with the help of the simple and rapid GU value calculation of this new application. 28844706 2 82 theme complex 300:306 arg1 carbohydrates 308:320 complex carbohydrates 300:320 complex carbohydrates 300:320 One of the frequently used methods for the analysis of complex carbohydrates is capillary electrophoresis with laser induced fluorescent detection (CE-LIF). 28844706 8 83 theme fluorescent 1548:1558 arg1 detection 1560:1568 laser induced fluorescent detection 1534:1568 laser induced fluorescent detection (CE-LIF) 1534:1577 One of the frequently used methods for the analysis of complex carbohydrates is capillary electrophoresis with laser induced fluorescent detection (CE-LIF). 28844706 8 83 theme fluorescent 1548:1558 arg1 CE-LIF 1571:1576 CE-LIF 1571:1576 CE-LIF 1571:1576 One of the frequently used methods for the analysis of complex carbohydrates is capillary electrophoresis with laser induced fluorescent detection (CE-LIF). 28844706 9 84 theme excellent 1634:1642 arg1 sensitivity 1644:1654 excellent sensitivity 1634:1654 excellent sensitivity capable of discriminating between closely related positional and linkage carbohydrate isomers 1634:1748 CE-LIF is a high resolution separation technique with excellent sensitivity capable of discriminating between closely related positional and linkage carbohydrate isomers. 28844706 13 85 theme routine 2568:2574 arg1 analysis 2576:2583 high-throughput routine analysis 2552:2583 high-throughput routine analysis 2552:2583 After very short training period, the software can be used readily for cutting-edge glycomics of exploratory research or high-throughput routine analysis. 28844706 5 86 theme GU 898:899 arg1 values 901:906 GU values 898:906 GU values for all sample components of interest 898:944 This tutorial introduces the practical use of the GUcal application, a recently developed glycoinformatics tool, which automatically calculates GU values for all sample components of interest in an electropherogram using either the bracketing standard approach or the recently published triple internal standard method. 28844706 11 87 from paper 1908:1912 arg1 application 1949:1959 the recently disseminated GUcal application 1917:1959 the recently disseminated GUcal application 1917:1959 According to our best knowledge, this is the first tutorial paper on the recently disseminated GUcal application, which automatically calculates GU values for all sample components of interest in an electropherogram using either the bracketing standard approach or the new triple internal standard method. 28844706 4 88 theme unit 704:707 arg1 values 714:719 their glucose unit (GU) values 690:719 their glucose unit (GU) values 690:719 Individual glycan structures corresponding to the separated peaks in an electropherogram are identified according to their glucose unit (GU) values by mining the built in database. 28844706 11 89 theme bracketing 2081:2090 arg1 approach 2101:2108 the bracketing standard approach 2077:2108 the bracketing standard approach 2077:2108 According to our best knowledge, this is the first tutorial paper on the recently disseminated GUcal application, which automatically calculates GU values for all sample components of interest in an electropherogram using either the bracketing standard approach or the new triple internal standard method. 28844706 2 90 theme used 267:270 arg1 methods 272:278 the frequently used methods 252:278 the frequently used methods for the analysis of complex carbohydrates 252:320 One of the frequently used methods for the analysis of complex carbohydrates is capillary electrophoresis with laser induced fluorescent detection (CE-LIF). 28844706 9 91 theme high 1592:1595 arg1 technique 1619:1627 a high resolution separation technique 1590:1627 a high resolution separation technique with excellent sensitivity capable of discriminating between closely related positional and linkage carbohydrate isomers 1590:1748 CE-LIF is a high resolution separation technique with excellent sensitivity capable of discriminating between closely related positional and linkage carbohydrate isomers. 28844706 9 91 theme high 1592:1595 arg1 CE-LIF 1580:1585 CE-LIF 1580:1585 CE-LIF 1580:1585 CE-LIF is a high resolution separation technique with excellent sensitivity capable of discriminating between closely related positional and linkage carbohydrate isomers. 28844706 6 92 theme worked 1089:1094 arg1 example 1096:1102 a worked example 1087:1102 a worked example 1087:1102 Furthermore, a worked example demonstrates the way glycan structural elucidation of human immunoglobulin G is processed with the help of this simple and rapid GU value calculation application. 28844706 7 93 from something 1309:1317 arg1 years 1355:1359 recent years 1348:1359 recent years 1348:1359 SIGNIFICANCE Biopharmaceuticals have seen something of tremendous development in recent years, which governs the parallel blooming of analytical glycomics. 28844706 9 94 theme separation 1608:1617 arg1 technique 1619:1627 a high resolution separation technique 1590:1627 a high resolution separation technique with excellent sensitivity capable of discriminating between closely related positional and linkage carbohydrate isomers 1590:1748 CE-LIF is a high resolution separation technique with excellent sensitivity capable of discriminating between closely related positional and linkage carbohydrate isomers. 28844706 9 94 theme separation 1608:1617 arg1 CE-LIF 1580:1585 CE-LIF 1580:1585 CE-LIF 1580:1585 CE-LIF is a high resolution separation technique with excellent sensitivity capable of discriminating between closely related positional and linkage carbohydrate isomers. 28844706 9 95 dep positional 1706:1715 arg1 isomers 1742:1748 carbohydrate isomers 1729:1748 carbohydrate isomers 1729:1748 CE-LIF is a high resolution separation technique with excellent sensitivity capable of discriminating between closely related positional and linkage carbohydrate isomers. 28844706 5 96 theme GUcal 804:808 arg1 tool 861:864 a recently developed glycoinformatics tool 823:864 a recently developed glycoinformatics tool 823:864 This tutorial introduces the practical use of the GUcal application, a recently developed glycoinformatics tool, which automatically calculates GU values for all sample components of interest in an electropherogram using either the bracketing standard approach or the recently published triple internal standard method. 28844706 5 96 theme GUcal 804:808 arg1 application 810:820 the GUcal application 800:820 the GUcal application 800:820 This tutorial introduces the practical use of the GUcal application, a recently developed glycoinformatics tool, which automatically calculates GU values for all sample components of interest in an electropherogram using either the bracketing standard approach or the recently published triple internal standard method. 28844706 12 97 theme application 2418:2428 arg1 calculation 2394:2404 the simple and rapid GU value calculation 2364:2404 the simple and rapid GU value calculation of this new application 2364:2428 On the top the step-by-step instruction how to use the application, the paper includes a worked example demonstrates the way glycan structure elucidation of human immunoglobulin G is processed with the help of the simple and rapid GU value calculation of this new application. 28844706 7 98 theme SIGNIFICANCE 1267:1278 arg1 Biopharmaceuticals 1280:1297 SIGNIFICANCE Biopharmaceuticals 1267:1297 SIGNIFICANCE Biopharmaceuticals 1267:1297 SIGNIFICANCE Biopharmaceuticals have seen something of tremendous development in recent years, which governs the parallel blooming of analytical glycomics. 28844706 12 99 theme glycan 2279:2284 arg1 structure 2286:2294 the way glycan structure 2271:2294 the way glycan structure elucidation of human immunoglobulin G is processed with the help of the simple and rapid GU value calculation of this new application 2271:2428 On the top the step-by-step instruction how to use the application, the paper includes a worked example demonstrates the way glycan structure elucidation of human immunoglobulin G is processed with the help of the simple and rapid GU value calculation of this new application. 28844706 13 100 theme high-throughput 2552:2566 arg1 analysis 2576:2583 high-throughput routine analysis 2552:2583 high-throughput routine analysis 2552:2583 After very short training period, the software can be used readily for cutting-edge glycomics of exploratory research or high-throughput routine analysis. 28844706 12 101 theme GU 2385:2386 arg1 calculation 2394:2404 the simple and rapid GU value calculation 2364:2404 the simple and rapid GU value calculation of this new application 2364:2428 On the top the step-by-step instruction how to use the application, the paper includes a worked example demonstrates the way glycan structure elucidation of human immunoglobulin G is processed with the help of the simple and rapid GU value calculation of this new application. 28844706 9 102 with technique 1619:1627 arg1 sensitivity 1644:1654 excellent sensitivity 1634:1654 excellent sensitivity capable of discriminating between closely related positional and linkage carbohydrate isomers 1634:1748 CE-LIF is a high resolution separation technique with excellent sensitivity capable of discriminating between closely related positional and linkage carbohydrate isomers. 28844706 2 103 theme capillary 325:333 arg1 electrophoresis 335:349 capillary electrophoresis 325:349 capillary electrophoresis with laser induced fluorescent detection (CE-LIF) 325:399 One of the frequently used methods for the analysis of complex carbohydrates is capillary electrophoresis with laser induced fluorescent detection (CE-LIF). 28844706 5 104 theme practical 783:791 arg1 use 793:795 the practical use 779:795 the practical use of the GUcal application, a recently developed glycoinformatics tool, which automatically calculates GU values for all sample components of interest in an electropherogram using either the bracketing standard approach or the recently published triple internal standard method 779:1071 This tutorial introduces the practical use of the GUcal application, a recently developed glycoinformatics tool, which automatically calculates GU values for all sample components of interest in an electropherogram using either the bracketing standard approach or the recently published triple internal standard method. 28844706 5 105 theme published 1031:1039 arg1 method 1066:1071 the recently published triple internal standard method 1018:1071 the recently published triple internal standard method 1018:1071 This tutorial introduces the practical use of the GUcal application, a recently developed glycoinformatics tool, which automatically calculates GU values for all sample components of interest in an electropherogram using either the bracketing standard approach or the recently published triple internal standard method. 28844706 11 106 theme first 1893:1897 arg1 this 1881:1884 this 1881:1884 this 1881:1884 According to our best knowledge, this is the first tutorial paper on the recently disseminated GUcal application, which automatically calculates GU values for all sample components of interest in an electropherogram using either the bracketing standard approach or the new triple internal standard method. 28844706 11 106 theme first 1893:1897 arg1 paper 1908:1912 the first tutorial paper 1889:1912 the first tutorial paper on the recently disseminated GUcal application, which automatically calculates GU values for all sample components of interest in an electropherogram using either the bracketing standard approach or the new triple internal standard method 1889:2151 According to our best knowledge, this is the first tutorial paper on the recently disseminated GUcal application, which automatically calculates GU values for all sample components of interest in an electropherogram using either the bracketing standard approach or the new triple internal standard method. 28844706 12 107 theme simple 2368:2373 arg1 calculation 2394:2404 the simple and rapid GU value calculation 2364:2404 the simple and rapid GU value calculation of this new application 2364:2428 On the top the step-by-step instruction how to use the application, the paper includes a worked example demonstrates the way glycan structure elucidation of human immunoglobulin G is processed with the help of the simple and rapid GU value calculation of this new application. 28844706 3 108 theme excellent 456:464 arg1 sensitivity 466:476 excellent sensitivity 456:476 excellent sensitivity capable of discriminating between closely related positional and linkage carbohydrate isomers 456:570 CE-LIF is a high resolution separation technique with excellent sensitivity capable of discriminating between closely related positional and linkage carbohydrate isomers. 28844706 5 109 theme glycoinformatics 844:859 arg1 tool 861:864 a recently developed glycoinformatics tool 823:864 a recently developed glycoinformatics tool 823:864 This tutorial introduces the practical use of the GUcal application, a recently developed glycoinformatics tool, which automatically calculates GU values for all sample components of interest in an electropherogram using either the bracketing standard approach or the recently published triple internal standard method. 28844706 5 109 theme glycoinformatics 844:859 arg1 application 810:820 the GUcal application 800:820 the GUcal application 800:820 This tutorial introduces the practical use of the GUcal application, a recently developed glycoinformatics tool, which automatically calculates GU values for all sample components of interest in an electropherogram using either the bracketing standard approach or the recently published triple internal standard method. 28844706 5 110 theme bracketing 986:995 arg1 approach 1006:1013 the bracketing standard approach 982:1013 the bracketing standard approach 982:1013 This tutorial introduces the practical use of the GUcal application, a recently developed glycoinformatics tool, which automatically calculates GU values for all sample components of interest in an electropherogram using either the bracketing standard approach or the recently published triple internal standard method. 28844706 6 111 theme structural 1132:1141 arg1 elucidation 1143:1153 glycan structural elucidation 1125:1153 glycan structural elucidation of human immunoglobulin G 1125:1179 Furthermore, a worked example demonstrates the way glycan structural elucidation of human immunoglobulin G is processed with the help of this simple and rapid GU value calculation application. 28844706 11 112 theme sample 2011:2016 arg1 components 2018:2027 all sample components 2007:2027 all sample components of interest 2007:2039 According to our best knowledge, this is the first tutorial paper on the recently disseminated GUcal application, which automatically calculates GU values for all sample components of interest in an electropherogram using either the bracketing standard approach or the new triple internal standard method. 28844706 8 113 theme methods 1450:1456 arg1 methods 1450:1456 the frequently used methods 1430:1456 the frequently used methods for the analysis of complex carbohydrates 1430:1498 One of the frequently used methods for the analysis of complex carbohydrates is capillary electrophoresis with laser induced fluorescent detection (CE-LIF). 28844706 8 113 theme methods 1450:1456 arg1 One 1423:1425 One 1423:1425 One 1423:1425 One of the frequently used methods for the analysis of complex carbohydrates is capillary electrophoresis with laser induced fluorescent detection (CE-LIF). 28844706 11 114 theme interest 2032:2039 arg1 components 2018:2027 all sample components 2007:2027 all sample components of interest 2007:2039 According to our best knowledge, this is the first tutorial paper on the recently disseminated GUcal application, which automatically calculates GU values for all sample components of interest in an electropherogram using either the bracketing standard approach or the new triple internal standard method. 28844706 0 115 theme N-linked 29:36 arg1 carbohydrates 38:50 N-linked carbohydrates 29:50 N-linked carbohydrates using the GUcal application 29:78 Structural identification of N-linked carbohydrates using the GUcal application: A tutorial. 28844706 1 116 theme recent 96:101 arg1 years 103:107 recent years 96:107 recent years 96:107 In recent years, analytical glycomics gained a significant role due to the rapidly increasing number of glycoproteins introduced as biopharmaceuticals. 28844706 4 117 theme separated 623:631 arg1 peaks 633:637 the separated peaks 619:637 the separated peaks in an electropherogram 619:660 Individual glycan structures corresponding to the separated peaks in an electropherogram are identified according to their glucose unit (GU) values by mining the built in database. 28844706 8 118 theme used 1445:1448 arg1 methods 1450:1456 the frequently used methods 1430:1456 the frequently used methods for the analysis of complex carbohydrates 1430:1498 One of the frequently used methods for the analysis of complex carbohydrates is capillary electrophoresis with laser induced fluorescent detection (CE-LIF). 28844706 10 119 theme bioinformatics 1807:1820 arg1 tools 1822:1826 the related bioinformatics tools 1795:1826 the related bioinformatics tools 1795:1826 While CE instrumentation is well developed, the related bioinformatics tools are lagging behind. 28844706 1 120 theme glycoproteins 197:209 arg1 number 187:192 the rapidly increasing number 164:192 the rapidly increasing number of glycoproteins introduced as biopharmaceuticals 164:242 In recent years, analytical glycomics gained a significant role due to the rapidly increasing number of glycoproteins introduced as biopharmaceuticals. 28844706 3 121 theme resolution 419:428 arg1 CE-LIF 402:407 CE-LIF 402:407 CE-LIF 402:407 CE-LIF is a high resolution separation technique with excellent sensitivity capable of discriminating between closely related positional and linkage carbohydrate isomers. 28844706 3 121 theme resolution 419:428 arg1 technique 441:449 a high resolution separation technique 412:449 a high resolution separation technique with excellent sensitivity capable of discriminating between closely related positional and linkage carbohydrate isomers 412:570 CE-LIF is a high resolution separation technique with excellent sensitivity capable of discriminating between closely related positional and linkage carbohydrate isomers. 28844706 4 122 theme Individual 573:582 arg1 structures 591:600 Individual glycan structures 573:600 Individual glycan structures corresponding to the separated peaks in an electropherogram 573:660 Individual glycan structures corresponding to the separated peaks in an electropherogram are identified according to their glucose unit (GU) values by mining the built in database. 28844706 12 123 theme human 2311:2315 arg1 G 2332:2332 human immunoglobulin G 2311:2332 human immunoglobulin G 2311:2332 On the top the step-by-step instruction how to use the application, the paper includes a worked example demonstrates the way glycan structure elucidation of human immunoglobulin G is processed with the help of the simple and rapid GU value calculation of this new application. 28844706 3 124 theme capable 478:484 arg1 sensitivity 466:476 excellent sensitivity 456:476 excellent sensitivity capable of discriminating between closely related positional and linkage carbohydrate isomers 456:570 CE-LIF is a high resolution separation technique with excellent sensitivity capable of discriminating between closely related positional and linkage carbohydrate isomers. 28844706 0 125 theme GUcal 62:66 arg1 application 68:78 the GUcal application 58:78 the GUcal application 58:78 Structural identification of N-linked carbohydrates using the GUcal application: A tutorial. 28844706 9 126 theme carbohydrate 1729:1740 arg1 isomers 1742:1748 carbohydrate isomers 1729:1748 carbohydrate isomers 1729:1748 CE-LIF is a high resolution separation technique with excellent sensitivity capable of discriminating between closely related positional and linkage carbohydrate isomers. 28844706 8 127 theme carbohydrates 1486:1498 arg1 analysis 1466:1473 the analysis 1462:1473 the analysis of complex carbohydrates 1462:1498 One of the frequently used methods for the analysis of complex carbohydrates is capillary electrophoresis with laser induced fluorescent detection (CE-LIF). 28844706 5 128 theme internal 1048:1055 arg1 method 1066:1071 the recently published triple internal standard method 1018:1071 the recently published triple internal standard method 1018:1071 This tutorial introduces the practical use of the GUcal application, a recently developed glycoinformatics tool, which automatically calculates GU values for all sample components of interest in an electropherogram using either the bracketing standard approach or the recently published triple internal standard method. 28844706 3 129 dep positional 528:537 arg1 isomers 564:570 carbohydrate isomers 551:570 carbohydrate isomers 551:570 CE-LIF is a high resolution separation technique with excellent sensitivity capable of discriminating between closely related positional and linkage carbohydrate isomers. 28844706 8 130 theme capillary 1503:1511 arg1 electrophoresis 1513:1527 capillary electrophoresis 1503:1527 capillary electrophoresis with laser induced fluorescent detection (CE-LIF) 1503:1577 One of the frequently used methods for the analysis of complex carbohydrates is capillary electrophoresis with laser induced fluorescent detection (CE-LIF). 28844706 6 131 theme G 1179:1179 arg1 elucidation 1143:1153 glycan structural elucidation 1125:1153 glycan structural elucidation of human immunoglobulin G 1125:1179 Furthermore, a worked example demonstrates the way glycan structural elucidation of human immunoglobulin G is processed with the help of this simple and rapid GU value calculation application. 28844706 0 132 dep identification 11:24 arg1 tutorial 83:90 A tutorial 81:90 Structural identification of N-linked carbohydrates using the GUcal application: A tutorial. 0:91 Structural identification of N-linked carbohydrates using the GUcal application: A tutorial. 28844706 6 133 dep the 1199:1201 arg1 help 1203:1206 help 1203:1206 help 1203:1206 Furthermore, a worked example demonstrates the way glycan structural elucidation of human immunoglobulin G is processed with the help of this simple and rapid GU value calculation application. 28811589 5 0 theme IgG1 814:817 arg1 RBC 786:788 the N-linked RBC 773:788 the N-linked RBC autoantibody and plasma IgG1 Fc-glycosylation in relation to occurrence of hemolysis for 103 patients with a positive direct antiglobulin test (DAT) 773:937 We investigated by mass spectrometry the N-linked RBC autoantibody and plasma IgG1 Fc-glycosylation in relation to occurrence of hemolysis for 103 patients with a positive direct antiglobulin test (DAT). 28811589 5 0 theme IgG1 814:817 arg1 Fc-glycosylation 819:834 plasma IgG1 Fc-glycosylation 807:834 plasma IgG1 Fc-glycosylation 807:834 We investigated by mass spectrometry the N-linked RBC autoantibody and plasma IgG1 Fc-glycosylation in relation to occurrence of hemolysis for 103 patients with a positive direct antiglobulin test (DAT). 28811589 6 1 theme total 957:961 arg1 IgG1 963:966 total IgG1 957:966 total IgG1 purified from plasma of patients with RBC-bound antibodies 957:1025 We observed that total IgG1 purified from plasma of patients with RBC-bound antibodies showed significantly decreased galactosylation and sialylation levels compared to healthy controls, similar to what previously has been shown for other autoimmune diseases. 28811589 9 2 theme Fc-glycoprofiles 1483:1498 arg1 Analysis 1462:1469 Analysis 1462:1469 Analysis of anti-RBC Fc-glycoprofiles 1462:1498 Analysis of anti-RBC Fc-glycoprofiles suggested that lower bisection and higher galactosylation associate with lower Hb levels. 28811589 7 3 theme bisection 1312:1320 arg1 levels 1322:1327 lower bisection levels 1306:1327 lower bisection levels 1306:1327 The anti-RBC- autoantibodies showed a profile with even lower galactosylation, but higher sialylation and lower bisection levels. 28811589 7 4 dep lower 1256:1260 arg1 galactosylation 1262:1276 galactosylation 1262:1276 galactosylation 1262:1276 The anti-RBC- autoantibodies showed a profile with even lower galactosylation, but higher sialylation and lower bisection levels. 28811589 4 5 theme IgG1 598:601 arg1 galactosylation 603:617 plasma IgG1 galactosylation 591:617 plasma IgG1 galactosylation 591:617 It is known that in autoimmune diseases plasma IgG1 galactosylation and sialylation are lowered, but Fc-glycosylation of RBC-specific autoantibodies has never been thoroughly analyzed. 28811589 6 6 dep showed 1027:1032 arg1 decreased 1048:1056 decreased 1048:1056 decreased 1048:1056 We observed that total IgG1 purified from plasma of patients with RBC-bound antibodies showed significantly decreased galactosylation and sialylation levels compared to healthy controls, similar to what previously has been shown for other autoimmune diseases. 28811589 7 7 with levels 1322:1327 arg1 sialylation 1290:1300 even lower galactosylation, but higher sialylation 1251:1300 even lower galactosylation, but higher sialylation 1251:1300 The anti-RBC- autoantibodies showed a profile with even lower galactosylation, but higher sialylation and lower bisection levels. 28811589 7 8 with profile 1238:1244 arg1 sialylation 1290:1300 even lower galactosylation, but higher sialylation 1251:1300 even lower galactosylation, but higher sialylation 1251:1300 The anti-RBC- autoantibodies showed a profile with even lower galactosylation, but higher sialylation and lower bisection levels. 28811589 1 9 theme red 162:164 arg1 RBC 179:181 RBC 179:181 RBC 179:181 Autoimmune hemolytic anemia (AIHA) is a potentially severe disease in which red blood cells (RBC) are destroyed by IgG anti-RBC autoantibodies which can lead to hemolysis. 28811589 1 9 theme red 162:164 arg1 cells 172:176 red blood cells 162:176 red blood cells (RBC) 162:182 Autoimmune hemolytic anemia (AIHA) is a potentially severe disease in which red blood cells (RBC) are destroyed by IgG anti-RBC autoantibodies which can lead to hemolysis. 28811589 4 10 theme plasma 591:596 arg1 galactosylation 603:617 plasma IgG1 galactosylation 591:617 plasma IgG1 galactosylation 591:617 It is known that in autoimmune diseases plasma IgG1 galactosylation and sialylation are lowered, but Fc-glycosylation of RBC-specific autoantibodies has never been thoroughly analyzed. 28811589 7 11 theme higher 1283:1288 arg1 sialylation 1290:1300 even lower galactosylation, but higher sialylation 1251:1300 even lower galactosylation, but higher sialylation 1251:1300 The anti-RBC- autoantibodies showed a profile with even lower galactosylation, but higher sialylation and lower bisection levels. 28811589 5 12 theme N-linked 777:784 arg1 RBC 786:788 the N-linked RBC 773:788 the N-linked RBC autoantibody and plasma IgG1 Fc-glycosylation in relation to occurrence of hemolysis for 103 patients with a positive direct antiglobulin test (DAT) 773:937 We investigated by mass spectrometry the N-linked RBC autoantibody and plasma IgG1 Fc-glycosylation in relation to occurrence of hemolysis for 103 patients with a positive direct antiglobulin test (DAT). 28811589 5 12 theme N-linked 777:784 arg1 autoantibody 790:801 autoantibody 790:801 autoantibody 790:801 We investigated by mass spectrometry the N-linked RBC autoantibody and plasma IgG1 Fc-glycosylation in relation to occurrence of hemolysis for 103 patients with a positive direct antiglobulin test (DAT). 28811589 5 12 theme N-linked 777:784 arg1 Fc-glycosylation 819:834 plasma IgG1 Fc-glycosylation 807:834 plasma IgG1 Fc-glycosylation 807:834 We investigated by mass spectrometry the N-linked RBC autoantibody and plasma IgG1 Fc-glycosylation in relation to occurrence of hemolysis for 103 patients with a positive direct antiglobulin test (DAT). 28811589 8 13 dep alloantibodies 1345:1358 arg1 contrast 1333:1340 contrast 1333:1340 contrast 1333:1340 In contrast to alloantibodies against RBCs, RBC-bound IgG1 Fc-fucosylation was not different between healthy controls and patients. 28811589 6 14 with patients 992:999 arg1 antibodies 1016:1025 RBC-bound antibodies 1006:1025 RBC-bound antibodies 1006:1025 We observed that total IgG1 purified from plasma of patients with RBC-bound antibodies showed significantly decreased galactosylation and sialylation levels compared to healthy controls, similar to what previously has been shown for other autoimmune diseases. 28811589 5 15 theme direct 908:913 arg1 DAT 934:936 DAT 934:936 DAT 934:936 We investigated by mass spectrometry the N-linked RBC autoantibody and plasma IgG1 Fc-glycosylation in relation to occurrence of hemolysis for 103 patients with a positive direct antiglobulin test (DAT). 28811589 5 15 theme direct 908:913 arg1 test 928:931 a positive direct antiglobulin test 897:931 a positive direct antiglobulin test (DAT) 897:937 We investigated by mass spectrometry the N-linked RBC autoantibody and plasma IgG1 Fc-glycosylation in relation to occurrence of hemolysis for 103 patients with a positive direct antiglobulin test (DAT). 28811589 7 16 theme lower 1256:1260 arg1 sialylation 1290:1300 even lower galactosylation, but higher sialylation 1251:1300 even lower galactosylation, but higher sialylation 1251:1300 The anti-RBC- autoantibodies showed a profile with even lower galactosylation, but higher sialylation and lower bisection levels. 28811589 3 17 theme pathogenic 483:492 arg1 alloantibodies 494:507 the pathogenic alloantibodies 479:507 the pathogenic alloantibodies 479:507 The lowered core-fucosylation increases the affinity of the pathogenic alloantibodies to FcγRIIIa/b, and hence RBC destruction. 28811589 1 18 theme Autoimmune 86:95 arg1 AIHA 115:118 AIHA 115:118 AIHA 115:118 Autoimmune hemolytic anemia (AIHA) is a potentially severe disease in which red blood cells (RBC) are destroyed by IgG anti-RBC autoantibodies which can lead to hemolysis. 28811589 1 18 theme Autoimmune 86:95 arg1 disease 145:151 a potentially severe disease 124:151 a potentially severe disease in which red blood cells (RBC) are destroyed by IgG anti-RBC autoantibodies which can lead to hemolysis 124:255 Autoimmune hemolytic anemia (AIHA) is a potentially severe disease in which red blood cells (RBC) are destroyed by IgG anti-RBC autoantibodies which can lead to hemolysis. 28811589 1 18 theme Autoimmune 86:95 arg1 anemia 107:112 Autoimmune hemolytic anemia 86:112 Autoimmune hemolytic anemia (AIHA) 86:119 Autoimmune hemolytic anemia (AIHA) is a potentially severe disease in which red blood cells (RBC) are destroyed by IgG anti-RBC autoantibodies which can lead to hemolysis. 28811589 1 19 theme blood 166:170 arg1 RBC 179:181 RBC 179:181 RBC 179:181 Autoimmune hemolytic anemia (AIHA) is a potentially severe disease in which red blood cells (RBC) are destroyed by IgG anti-RBC autoantibodies which can lead to hemolysis. 28811589 1 19 theme blood 166:170 arg1 cells 172:176 red blood cells 162:176 red blood cells (RBC) 162:182 Autoimmune hemolytic anemia (AIHA) is a potentially severe disease in which red blood cells (RBC) are destroyed by IgG anti-RBC autoantibodies which can lead to hemolysis. 28811589 9 20 theme higher 1535:1540 arg1 galactosylation 1542:1556 higher galactosylation 1535:1556 higher galactosylation 1535:1556 Analysis of anti-RBC Fc-glycoprofiles suggested that lower bisection and higher galactosylation associate with lower Hb levels. 28811589 4 21 gly Fc-glycosylation 652:667 arg1 autoantibodies 685:698 RBC-specific autoantibodies 672:698 RBC-specific autoantibodies 672:698 It is known that in autoimmune diseases plasma IgG1 galactosylation and sialylation are lowered, but Fc-glycosylation of RBC-specific autoantibodies has never been thoroughly analyzed. 28811589 1 22 theme hemolytic 97:105 arg1 AIHA 115:118 AIHA 115:118 AIHA 115:118 Autoimmune hemolytic anemia (AIHA) is a potentially severe disease in which red blood cells (RBC) are destroyed by IgG anti-RBC autoantibodies which can lead to hemolysis. 28811589 1 22 theme hemolytic 97:105 arg1 disease 145:151 a potentially severe disease 124:151 a potentially severe disease in which red blood cells (RBC) are destroyed by IgG anti-RBC autoantibodies which can lead to hemolysis 124:255 Autoimmune hemolytic anemia (AIHA) is a potentially severe disease in which red blood cells (RBC) are destroyed by IgG anti-RBC autoantibodies which can lead to hemolysis. 28811589 1 22 theme hemolytic 97:105 arg1 anemia 107:112 Autoimmune hemolytic anemia 86:112 Autoimmune hemolytic anemia (AIHA) 86:119 Autoimmune hemolytic anemia (AIHA) is a potentially severe disease in which red blood cells (RBC) are destroyed by IgG anti-RBC autoantibodies which can lead to hemolysis. 28811589 2 23 theme increased 380:388 arg1 galactosylation 390:404 increased galactosylation 380:404 increased galactosylation 380:404 We recently found IgG Fc-glycosylation towards platelet and RBC alloantigens to be skewed towards decreased fucosylation, increased galactosylation and sialylation. 28811589 4 24 from diseases 582:589 arg1 lowered 639:645 lowered 639:645 lowered 639:645 It is known that in autoimmune diseases plasma IgG1 galactosylation and sialylation are lowered, but Fc-glycosylation of RBC-specific autoantibodies has never been thoroughly analyzed. 28811589 6 25 theme patients 992:999 arg1 plasma 982:987 plasma 982:987 plasma of patients with RBC-bound antibodies 982:1025 We observed that total IgG1 purified from plasma of patients with RBC-bound antibodies showed significantly decreased galactosylation and sialylation levels compared to healthy controls, similar to what previously has been shown for other autoimmune diseases. 28811589 5 26 with patients 883:890 arg1 DAT 934:936 DAT 934:936 DAT 934:936 We investigated by mass spectrometry the N-linked RBC autoantibody and plasma IgG1 Fc-glycosylation in relation to occurrence of hemolysis for 103 patients with a positive direct antiglobulin test (DAT). 28811589 5 26 with patients 883:890 arg1 test 928:931 a positive direct antiglobulin test 897:931 a positive direct antiglobulin test (DAT) 897:937 We investigated by mass spectrometry the N-linked RBC autoantibody and plasma IgG1 Fc-glycosylation in relation to occurrence of hemolysis for 103 patients with a positive direct antiglobulin test (DAT). 28811589 2 27 theme platelet 305:312 arg1 alloantigens 322:333 platelet and RBC alloantigens 305:333 platelet and RBC alloantigens 305:333 We recently found IgG Fc-glycosylation towards platelet and RBC alloantigens to be skewed towards decreased fucosylation, increased galactosylation and sialylation. 28811589 3 28 theme lowered 427:433 arg1 core-fucosylation 435:451 The lowered core-fucosylation 423:451 The lowered core-fucosylation 423:451 The lowered core-fucosylation increases the affinity of the pathogenic alloantibodies to FcγRIIIa/b, and hence RBC destruction. 28811589 5 29 theme hemolysis 865:873 arg1 occurrence 851:860 occurrence 851:860 occurrence of hemolysis for 103 patients with a positive direct antiglobulin test (DAT) 851:937 We investigated by mass spectrometry the N-linked RBC autoantibody and plasma IgG1 Fc-glycosylation in relation to occurrence of hemolysis for 103 patients with a positive direct antiglobulin test (DAT). 28811589 5 30 theme antiglobulin 915:926 arg1 DAT 934:936 DAT 934:936 DAT 934:936 We investigated by mass spectrometry the N-linked RBC autoantibody and plasma IgG1 Fc-glycosylation in relation to occurrence of hemolysis for 103 patients with a positive direct antiglobulin test (DAT). 28811589 5 30 theme antiglobulin 915:926 arg1 test 928:931 a positive direct antiglobulin test 897:931 a positive direct antiglobulin test (DAT) 897:937 We investigated by mass spectrometry the N-linked RBC autoantibody and plasma IgG1 Fc-glycosylation in relation to occurrence of hemolysis for 103 patients with a positive direct antiglobulin test (DAT). 28811589 6 31 theme galactosylation 1058:1072 arg1 levels 1090:1095 galactosylation and sialylation levels 1058:1095 galactosylation and sialylation levels 1058:1095 We observed that total IgG1 purified from plasma of patients with RBC-bound antibodies showed significantly decreased galactosylation and sialylation levels compared to healthy controls, similar to what previously has been shown for other autoimmune diseases. 28811589 9 32 theme lower 1573:1577 arg1 levels 1582:1587 lower Hb levels 1573:1587 lower Hb levels 1573:1587 Analysis of anti-RBC Fc-glycoprofiles suggested that lower bisection and higher galactosylation associate with lower Hb levels. 28811589 0 33 theme blood 28:32 arg1 autoantibodies 39:52 IgG1-anti-red blood cell autoantibodies 14:52 IgG1-anti-red blood cell autoantibodies 14:52 Patients with IgG1-anti-red blood cell autoantibodies show aberrant Fc-glycosylation. 28811589 6 34 theme RBC-bound 1006:1014 arg1 antibodies 1016:1025 RBC-bound antibodies 1006:1025 RBC-bound antibodies 1006:1025 We observed that total IgG1 purified from plasma of patients with RBC-bound antibodies showed significantly decreased galactosylation and sialylation levels compared to healthy controls, similar to what previously has been shown for other autoimmune diseases. 28811589 8 35 theme RBC-bound 1374:1382 arg1 Fc-fucosylation 1389:1403 RBC-bound IgG1 Fc-fucosylation 1374:1403 RBC-bound IgG1 Fc-fucosylation 1374:1403 In contrast to alloantibodies against RBCs, RBC-bound IgG1 Fc-fucosylation was not different between healthy controls and patients. 28811589 7 36 gly sialylation 1290:1300 arg1 profile 1238:1244 a profile 1236:1244 a profile with even lower galactosylation, but higher sialylation 1236:1300 The anti-RBC- autoantibodies showed a profile with even lower galactosylation, but higher sialylation and lower bisection levels. 28811589 7 36 gly sialylation 1290:1300 arg1 levels 1322:1327 lower bisection levels 1306:1327 lower bisection levels 1306:1327 The anti-RBC- autoantibodies showed a profile with even lower galactosylation, but higher sialylation and lower bisection levels. 28811589 9 37 theme Hb 1579:1580 arg1 levels 1582:1587 lower Hb levels 1573:1587 lower Hb levels 1573:1587 Analysis of anti-RBC Fc-glycoprofiles suggested that lower bisection and higher galactosylation associate with lower Hb levels. 28811589 0 38 theme IgG1-anti-red 14:26 arg1 autoantibodies 39:52 IgG1-anti-red blood cell autoantibodies 14:52 IgG1-anti-red blood cell autoantibodies 14:52 Patients with IgG1-anti-red blood cell autoantibodies show aberrant Fc-glycosylation. 28811589 5 39 from RBC 786:788 arg1 relation 839:846 relation 839:846 relation to occurrence of hemolysis for 103 patients with a positive direct antiglobulin test (DAT) 839:937 We investigated by mass spectrometry the N-linked RBC autoantibody and plasma IgG1 Fc-glycosylation in relation to occurrence of hemolysis for 103 patients with a positive direct antiglobulin test (DAT). 28811589 2 40 theme IgG 276:278 arg1 Fc-glycosylation 280:295 IgG Fc-glycosylation 276:295 IgG Fc-glycosylation towards platelet and RBC alloantigens 276:333 We recently found IgG Fc-glycosylation towards platelet and RBC alloantigens to be skewed towards decreased fucosylation, increased galactosylation and sialylation. 28811589 2 41 theme decreased 356:364 arg1 fucosylation 366:377 decreased fucosylation 356:377 decreased fucosylation 356:377 We recently found IgG Fc-glycosylation towards platelet and RBC alloantigens to be skewed towards decreased fucosylation, increased galactosylation and sialylation. 28811589 4 42 theme autoimmune 571:580 arg1 diseases 582:589 autoimmune diseases 571:589 autoimmune diseases 571:589 It is known that in autoimmune diseases plasma IgG1 galactosylation and sialylation are lowered, but Fc-glycosylation of RBC-specific autoantibodies has never been thoroughly analyzed. 28811589 5 43 theme mass 755:758 arg1 spectrometry 760:771 mass spectrometry 755:771 mass spectrometry 755:771 We investigated by mass spectrometry the N-linked RBC autoantibody and plasma IgG1 Fc-glycosylation in relation to occurrence of hemolysis for 103 patients with a positive direct antiglobulin test (DAT). 28811589 6 44 theme healthy 1109:1115 arg1 controls 1117:1124 healthy controls 1109:1124 healthy controls 1109:1124 We observed that total IgG1 purified from plasma of patients with RBC-bound antibodies showed significantly decreased galactosylation and sialylation levels compared to healthy controls, similar to what previously has been shown for other autoimmune diseases. 28811589 8 45 theme IgG1 1384:1387 arg1 Fc-fucosylation 1389:1403 RBC-bound IgG1 Fc-fucosylation 1374:1403 RBC-bound IgG1 Fc-fucosylation 1374:1403 In contrast to alloantibodies against RBCs, RBC-bound IgG1 Fc-fucosylation was not different between healthy controls and patients. 28811589 4 46 theme RBC-specific 672:683 arg1 autoantibodies 685:698 RBC-specific autoantibodies 672:698 RBC-specific autoantibodies 672:698 It is known that in autoimmune diseases plasma IgG1 galactosylation and sialylation are lowered, but Fc-glycosylation of RBC-specific autoantibodies has never been thoroughly analyzed. 28811589 0 47 theme cell 34:37 arg1 autoantibodies 39:52 IgG1-anti-red blood cell autoantibodies 14:52 IgG1-anti-red blood cell autoantibodies 14:52 Patients with IgG1-anti-red blood cell autoantibodies show aberrant Fc-glycosylation. 28811589 9 48 theme lower 1515:1519 arg1 bisection 1521:1529 lower bisection 1515:1529 lower bisection 1515:1529 Analysis of anti-RBC Fc-glycoprofiles suggested that lower bisection and higher galactosylation associate with lower Hb levels. 28811589 5 49 theme positive 899:906 arg1 DAT 934:936 DAT 934:936 DAT 934:936 We investigated by mass spectrometry the N-linked RBC autoantibody and plasma IgG1 Fc-glycosylation in relation to occurrence of hemolysis for 103 patients with a positive direct antiglobulin test (DAT). 28811589 5 49 theme positive 899:906 arg1 test 928:931 a positive direct antiglobulin test 897:931 a positive direct antiglobulin test (DAT) 897:937 We investigated by mass spectrometry the N-linked RBC autoantibody and plasma IgG1 Fc-glycosylation in relation to occurrence of hemolysis for 103 patients with a positive direct antiglobulin test (DAT). 28811589 0 50 theme aberrant 59:66 arg1 Fc-glycosylation 68:83 aberrant Fc-glycosylation 59:83 aberrant Fc-glycosylation 59:83 Patients with IgG1-anti-red blood cell autoantibodies show aberrant Fc-glycosylation. 28811589 5 51 dep RBC 786:788 arg1 RBC 786:788 the N-linked RBC 773:788 the N-linked RBC autoantibody and plasma IgG1 Fc-glycosylation in relation to occurrence of hemolysis for 103 patients with a positive direct antiglobulin test (DAT) 773:937 We investigated by mass spectrometry the N-linked RBC autoantibody and plasma IgG1 Fc-glycosylation in relation to occurrence of hemolysis for 103 patients with a positive direct antiglobulin test (DAT). 28811589 5 51 dep RBC 786:788 arg1 autoantibody 790:801 autoantibody 790:801 autoantibody 790:801 We investigated by mass spectrometry the N-linked RBC autoantibody and plasma IgG1 Fc-glycosylation in relation to occurrence of hemolysis for 103 patients with a positive direct antiglobulin test (DAT). 28811589 5 51 dep RBC 786:788 arg1 Fc-glycosylation 819:834 plasma IgG1 Fc-glycosylation 807:834 plasma IgG1 Fc-glycosylation 807:834 We investigated by mass spectrometry the N-linked RBC autoantibody and plasma IgG1 Fc-glycosylation in relation to occurrence of hemolysis for 103 patients with a positive direct antiglobulin test (DAT). 28811589 5 52 theme plasma 807:812 arg1 RBC 786:788 the N-linked RBC 773:788 the N-linked RBC autoantibody and plasma IgG1 Fc-glycosylation in relation to occurrence of hemolysis for 103 patients with a positive direct antiglobulin test (DAT) 773:937 We investigated by mass spectrometry the N-linked RBC autoantibody and plasma IgG1 Fc-glycosylation in relation to occurrence of hemolysis for 103 patients with a positive direct antiglobulin test (DAT). 28811589 5 52 theme plasma 807:812 arg1 Fc-glycosylation 819:834 plasma IgG1 Fc-glycosylation 807:834 plasma IgG1 Fc-glycosylation 807:834 We investigated by mass spectrometry the N-linked RBC autoantibody and plasma IgG1 Fc-glycosylation in relation to occurrence of hemolysis for 103 patients with a positive direct antiglobulin test (DAT). 28811589 6 53 theme autoimmune 1179:1188 arg1 diseases 1190:1197 other autoimmune diseases 1173:1197 other autoimmune diseases 1173:1197 We observed that total IgG1 purified from plasma of patients with RBC-bound antibodies showed significantly decreased galactosylation and sialylation levels compared to healthy controls, similar to what previously has been shown for other autoimmune diseases. 28811589 7 54 theme anti-RBC- 1204:1212 arg1 autoantibodies 1214:1227 The anti-RBC- autoantibodies 1200:1227 The anti-RBC- autoantibodies 1200:1227 The anti-RBC- autoantibodies showed a profile with even lower galactosylation, but higher sialylation and lower bisection levels. 28811589 3 55 theme alloantibodies 494:507 arg1 affinity 467:474 the affinity 463:474 the affinity of the pathogenic alloantibodies to FcγRIIIa/b, and hence RBC destruction 463:548 The lowered core-fucosylation increases the affinity of the pathogenic alloantibodies to FcγRIIIa/b, and hence RBC destruction. 28811589 0 56 with Patients 0:7 arg1 autoantibodies 39:52 IgG1-anti-red blood cell autoantibodies 14:52 IgG1-anti-red blood cell autoantibodies 14:52 Patients with IgG1-anti-red blood cell autoantibodies show aberrant Fc-glycosylation. 28811589 2 57 theme RBC 318:320 arg1 alloantigens 322:333 platelet and RBC alloantigens 305:333 platelet and RBC alloantigens 305:333 We recently found IgG Fc-glycosylation towards platelet and RBC alloantigens to be skewed towards decreased fucosylation, increased galactosylation and sialylation. 28811589 6 58 theme other 1173:1177 arg1 diseases 1190:1197 other autoimmune diseases 1173:1197 other autoimmune diseases 1173:1197 We observed that total IgG1 purified from plasma of patients with RBC-bound antibodies showed significantly decreased galactosylation and sialylation levels compared to healthy controls, similar to what previously has been shown for other autoimmune diseases. 28811589 1 59 theme IgG 201:203 arg1 autoantibodies 214:227 IgG anti-RBC autoantibodies 201:227 IgG anti-RBC autoantibodies which can lead to hemolysis 201:255 Autoimmune hemolytic anemia (AIHA) is a potentially severe disease in which red blood cells (RBC) are destroyed by IgG anti-RBC autoantibodies which can lead to hemolysis. 28811589 5 60 link N-linked 777:784 arg1 RBC 786:788 the N-linked RBC 773:788 the N-linked RBC autoantibody and plasma IgG1 Fc-glycosylation in relation to occurrence of hemolysis for 103 patients with a positive direct antiglobulin test (DAT) 773:937 We investigated by mass spectrometry the N-linked RBC autoantibody and plasma IgG1 Fc-glycosylation in relation to occurrence of hemolysis for 103 patients with a positive direct antiglobulin test (DAT). 28811589 5 60 link N-linked 777:784 arg1 autoantibody 790:801 autoantibody 790:801 autoantibody 790:801 We investigated by mass spectrometry the N-linked RBC autoantibody and plasma IgG1 Fc-glycosylation in relation to occurrence of hemolysis for 103 patients with a positive direct antiglobulin test (DAT). 28811589 5 60 link N-linked 777:784 arg1 Fc-glycosylation 819:834 plasma IgG1 Fc-glycosylation 807:834 plasma IgG1 Fc-glycosylation 807:834 We investigated by mass spectrometry the N-linked RBC autoantibody and plasma IgG1 Fc-glycosylation in relation to occurrence of hemolysis for 103 patients with a positive direct antiglobulin test (DAT). 28811589 8 61 theme healthy 1431:1437 arg1 controls 1439:1446 healthy controls 1431:1446 healthy controls 1431:1446 In contrast to alloantibodies against RBCs, RBC-bound IgG1 Fc-fucosylation was not different between healthy controls and patients. 28811589 1 62 theme severe 138:143 arg1 anemia 107:112 Autoimmune hemolytic anemia 86:112 Autoimmune hemolytic anemia (AIHA) 86:119 Autoimmune hemolytic anemia (AIHA) is a potentially severe disease in which red blood cells (RBC) are destroyed by IgG anti-RBC autoantibodies which can lead to hemolysis. 28811589 1 62 theme severe 138:143 arg1 disease 145:151 a potentially severe disease 124:151 a potentially severe disease in which red blood cells (RBC) are destroyed by IgG anti-RBC autoantibodies which can lead to hemolysis 124:255 Autoimmune hemolytic anemia (AIHA) is a potentially severe disease in which red blood cells (RBC) are destroyed by IgG anti-RBC autoantibodies which can lead to hemolysis. 28811589 1 63 theme anti-RBC 205:212 arg1 autoantibodies 214:227 IgG anti-RBC autoantibodies 201:227 IgG anti-RBC autoantibodies which can lead to hemolysis 201:255 Autoimmune hemolytic anemia (AIHA) is a potentially severe disease in which red blood cells (RBC) are destroyed by IgG anti-RBC autoantibodies which can lead to hemolysis. 28811589 7 64 theme lower 1306:1310 arg1 levels 1322:1327 lower bisection levels 1306:1327 lower bisection levels 1306:1327 The anti-RBC- autoantibodies showed a profile with even lower galactosylation, but higher sialylation and lower bisection levels. 28811589 3 65 theme RBC 534:536 arg1 destruction 538:548 RBC destruction 534:548 RBC destruction 534:548 The lowered core-fucosylation increases the affinity of the pathogenic alloantibodies to FcγRIIIa/b, and hence RBC destruction. 28811589 4 66 theme autoantibodies 685:698 arg1 Fc-glycosylation 652:667 Fc-glycosylation 652:667 Fc-glycosylation of RBC-specific autoantibodies 652:698 It is known that in autoimmune diseases plasma IgG1 galactosylation and sialylation are lowered, but Fc-glycosylation of RBC-specific autoantibodies has never been thoroughly analyzed. 28811589 6 67 theme sialylation 1078:1088 arg1 levels 1090:1095 galactosylation and sialylation levels 1058:1095 galactosylation and sialylation levels 1058:1095 We observed that total IgG1 purified from plasma of patients with RBC-bound antibodies showed significantly decreased galactosylation and sialylation levels compared to healthy controls, similar to what previously has been shown for other autoimmune diseases. 28811589 4 68 from lowered 639:645 arg1 diseases 582:589 autoimmune diseases 571:589 autoimmune diseases 571:589 It is known that in autoimmune diseases plasma IgG1 galactosylation and sialylation are lowered, but Fc-glycosylation of RBC-specific autoantibodies has never been thoroughly analyzed. 28811589 9 69 theme anti-RBC 1474:1481 arg1 Fc-glycoprofiles 1483:1498 anti-RBC Fc-glycoprofiles 1474:1498 anti-RBC Fc-glycoprofiles 1474:1498 Analysis of anti-RBC Fc-glycoprofiles suggested that lower bisection and higher galactosylation associate with lower Hb levels. 24366413 6 0 theme LNCaP 1030:1034 arg1 cells 1036:1040 prostate cancer LNCaP cells 1014:1040 prostate cancer LNCaP cells 1014:1040 The effects of reduced O-GlcNAc expression level on proliferation and invasion of prostate cancer LNCaP cells were examined using small interfering RNA (siRNA) targeting O-GlcNAc transferase (OGT), the enzyme responsible for O-GlcNAc biosynthesis. 24366413 11 1 theme cancer 2056:2061 arg1 cells 2063:2067 prostate cancer cells 2047:2067 prostate cancer cells 2047:2067 CONCLUSIONS These results indicate that O-GlcNAc expression level in prostate cancer cells is associated with poor prognosis of prostate cancer patients and likely enhances tumor cell proliferation and invasion. 24366413 1 2 theme protein 277:283 arg1 stability 285:293 protein stability 277:293 protein stability 277:293 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) is a glycan essential for fundamental cellular processes such as transcription/translation, nuclear transport, protein stability and protein-protein interactions. 24366413 6 3 theme prostate 1014:1021 arg1 cells 1036:1040 prostate cancer LNCaP cells 1014:1040 prostate cancer LNCaP cells 1014:1040 The effects of reduced O-GlcNAc expression level on proliferation and invasion of prostate cancer LNCaP cells were examined using small interfering RNA (siRNA) targeting O-GlcNAc transferase (OGT), the enzyme responsible for O-GlcNAc biosynthesis. 24366413 4 4 from level 561:565 arg1 cells 586:590 prostate cancer cells 570:590 prostate cancer cells 570:590 METHODS O-GlcNAc expression level in prostate cancer cells was determined by immunohistochemistry of prostate biopsy specimens obtained from 56 patients later treated with hormone deprivation therapy comparing with adjacent normal prostate glands in the same sections. 24366413 10 5 theme cell 1911:1914 arg1 invasion 1916:1923 tumor cell invasion 1905:1923 tumor cell invasion 1905:1923 Finally, siRNA-mediated OGT knockdown in LNCaP cells resulted in decreased expression of O-GlcNAc and promoted decreased proliferation and tumor cell invasion compared with control siRNA-transfected LNCaP cells. 24366413 4 6 theme adjacent 748:755 arg1 glands 773:778 adjacent normal prostate glands 748:778 adjacent normal prostate glands in the same sections 748:799 METHODS O-GlcNAc expression level in prostate cancer cells was determined by immunohistochemistry of prostate biopsy specimens obtained from 56 patients later treated with hormone deprivation therapy comparing with adjacent normal prostate glands in the same sections. 24366413 1 7 theme essential 178:186 arg1 β-N-acetylglucosamine 133:153 BACKGROUND O-linked β-N-acetylglucosamine 113:153 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) 113:164 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) is a glycan essential for fundamental cellular processes such as transcription/translation, nuclear transport, protein stability and protein-protein interactions. 24366413 1 7 theme essential 178:186 arg1 glycan 171:176 a glycan 169:176 a glycan essential for fundamental cellular processes such as transcription/translation, nuclear transport, protein stability and protein-protein interactions 169:326 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) is a glycan essential for fundamental cellular processes such as transcription/translation, nuclear transport, protein stability and protein-protein interactions. 24366413 4 8 theme prostate 764:771 arg1 glands 773:778 adjacent normal prostate glands 748:778 adjacent normal prostate glands in the same sections 748:799 METHODS O-GlcNAc expression level in prostate cancer cells was determined by immunohistochemistry of prostate biopsy specimens obtained from 56 patients later treated with hormone deprivation therapy comparing with adjacent normal prostate glands in the same sections. 24366413 7 9 theme cancer 1197:1202 arg1 cells 1204:1208 cancer cells 1197:1208 cancer cells showing stronger cytoplasmic staining than normal prostate glands 1197:1274 RESULTS Defining cancer cells showing stronger cytoplasmic staining than normal prostate glands as overexpression of O-GlcNAc, 39% of prostate cancer patients were categorized as overexpression. 24366413 10 10 theme control 1939:1945 arg1 cells 1971:1975 control siRNA-transfected LNCaP cells 1939:1975 control siRNA-transfected LNCaP cells 1939:1975 Finally, siRNA-mediated OGT knockdown in LNCaP cells resulted in decreased expression of O-GlcNAc and promoted decreased proliferation and tumor cell invasion compared with control siRNA-transfected LNCaP cells. 24366413 1 11 theme fundamental 192:202 arg1 processes 213:221 fundamental cellular processes 192:221 fundamental cellular processes such as transcription/translation, nuclear transport, protein stability and protein-protein interactions 192:326 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) is a glycan essential for fundamental cellular processes such as transcription/translation, nuclear transport, protein stability and protein-protein interactions. 24366413 1 11 theme fundamental 192:202 arg1 transcription/translation 231:255 transcription/translation 231:255 transcription/translation 231:255 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) is a glycan essential for fundamental cellular processes such as transcription/translation, nuclear transport, protein stability and protein-protein interactions. 24366413 1 11 theme fundamental 192:202 arg1 transport 266:274 nuclear transport 258:274 nuclear transport 258:274 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) is a glycan essential for fundamental cellular processes such as transcription/translation, nuclear transport, protein stability and protein-protein interactions. 24366413 1 11 theme fundamental 192:202 arg1 stability 285:293 protein stability 277:293 protein stability 277:293 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) is a glycan essential for fundamental cellular processes such as transcription/translation, nuclear transport, protein stability and protein-protein interactions. 24366413 1 11 theme fundamental 192:202 arg1 interactions 315:326 protein-protein interactions 299:326 protein-protein interactions 299:326 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) is a glycan essential for fundamental cellular processes such as transcription/translation, nuclear transport, protein stability and protein-protein interactions. 24366413 4 12 theme deprivation 713:723 arg1 therapy 725:731 hormone deprivation therapy 705:731 hormone deprivation therapy comparing with adjacent normal prostate glands in the same sections 705:799 METHODS O-GlcNAc expression level in prostate cancer cells was determined by immunohistochemistry of prostate biopsy specimens obtained from 56 patients later treated with hormone deprivation therapy comparing with adjacent normal prostate glands in the same sections. 24366413 6 13 theme interfering 1068:1078 arg1 RNA 1080:1082 small interfering RNA 1062:1082 small interfering RNA (siRNA) targeting O-GlcNAc transferase (OGT), the enzyme responsible for O-GlcNAc biosynthesis 1062:1177 The effects of reduced O-GlcNAc expression level on proliferation and invasion of prostate cancer LNCaP cells were examined using small interfering RNA (siRNA) targeting O-GlcNAc transferase (OGT), the enzyme responsible for O-GlcNAc biosynthesis. 24366413 6 13 theme interfering 1068:1078 arg1 siRNA 1085:1089 siRNA 1085:1089 siRNA 1085:1089 The effects of reduced O-GlcNAc expression level on proliferation and invasion of prostate cancer LNCaP cells were examined using small interfering RNA (siRNA) targeting O-GlcNAc transferase (OGT), the enzyme responsible for O-GlcNAc biosynthesis. 24366413 8 14 theme univariate 1587:1596 arg1 analysis 1611:1618 the Kaplan-Meier and P=0.0021 for Cox univariate hazard model analysis 1549:1618 analysis 1611:1618 The Kaplan-Meier and Cox proportional hazards methods with univariate model analysis revealed that O-GlcNAc overexpression was associated with overall survival (P=0.0012 for the Kaplan-Meier and P=0.0021 for Cox univariate hazard model analysis). 24366413 8 15 theme proportional 1400:1411 arg1 hazards 1413:1419 Cox proportional hazards 1396:1419 Cox proportional hazards 1396:1419 The Kaplan-Meier and Cox proportional hazards methods with univariate model analysis revealed that O-GlcNAc overexpression was associated with overall survival (P=0.0012 for the Kaplan-Meier and P=0.0021 for Cox univariate hazard model analysis). 24366413 11 16 theme tumor 2151:2155 arg1 cell 2157:2160 tumor cell proliferation and invasion 2151:2187 tumor cell proliferation and invasion 2151:2187 CONCLUSIONS These results indicate that O-GlcNAc expression level in prostate cancer cells is associated with poor prognosis of prostate cancer patients and likely enhances tumor cell proliferation and invasion. 24366413 8 17 theme model 1605:1609 arg1 analysis 1611:1618 the Kaplan-Meier and P=0.0021 for Cox univariate hazard model analysis 1549:1618 analysis 1611:1618 The Kaplan-Meier and Cox proportional hazards methods with univariate model analysis revealed that O-GlcNAc overexpression was associated with overall survival (P=0.0012 for the Kaplan-Meier and P=0.0021 for Cox univariate hazard model analysis). 24366413 10 18 theme LNCaP 1965:1969 arg1 cells 1971:1975 control siRNA-transfected LNCaP cells 1939:1975 control siRNA-transfected LNCaP cells 1939:1975 Finally, siRNA-mediated OGT knockdown in LNCaP cells resulted in decreased expression of O-GlcNAc and promoted decreased proliferation and tumor cell invasion compared with control siRNA-transfected LNCaP cells. 24366413 1 19 theme O-linked 124:131 arg1 β-N-acetylglucosamine 133:153 BACKGROUND O-linked β-N-acetylglucosamine 113:153 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) 113:164 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) is a glycan essential for fundamental cellular processes such as transcription/translation, nuclear transport, protein stability and protein-protein interactions. 24366413 1 19 theme O-linked 124:131 arg1 glycan 171:176 a glycan 169:176 a glycan essential for fundamental cellular processes such as transcription/translation, nuclear transport, protein stability and protein-protein interactions 169:326 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) is a glycan essential for fundamental cellular processes such as transcription/translation, nuclear transport, protein stability and protein-protein interactions. 24366413 1 19 theme O-linked 124:131 arg1 O-GlcNAc 156:163 O-GlcNAc 156:163 O-GlcNAc 156:163 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) is a glycan essential for fundamental cellular processes such as transcription/translation, nuclear transport, protein stability and protein-protein interactions. 24366413 8 20 theme univariate 1434:1443 arg1 analysis 1451:1458 univariate model analysis 1434:1458 univariate model analysis 1434:1458 The Kaplan-Meier and Cox proportional hazards methods with univariate model analysis revealed that O-GlcNAc overexpression was associated with overall survival (P=0.0012 for the Kaplan-Meier and P=0.0021 for Cox univariate hazard model analysis). 24366413 9 21 theme only 1652:1655 arg1 O-GlcNAc 1635:1642 O-GlcNAc 1635:1642 O-GlcNAc 1635:1642 Furthermore, O-GlcNAc was the only item in which a significant difference was observed at overall survival by multivariate analysis (P=0.0475). 24366413 9 21 theme only 1652:1655 arg1 item 1657:1660 the only item 1648:1660 the only item in which a significant difference was observed at overall survival by multivariate analysis (P=0.0475) 1648:1763 Furthermore, O-GlcNAc was the only item in which a significant difference was observed at overall survival by multivariate analysis (P=0.0475). 24366413 11 22 theme cancer 2115:2120 arg1 patients 2122:2129 prostate cancer patients 2106:2129 prostate cancer patients 2106:2129 CONCLUSIONS These results indicate that O-GlcNAc expression level in prostate cancer cells is associated with poor prognosis of prostate cancer patients and likely enhances tumor cell proliferation and invasion. 24366413 11 23 theme poor 2088:2091 arg1 prognosis 2093:2101 poor prognosis 2088:2101 poor prognosis of prostate cancer patients 2088:2129 CONCLUSIONS These results indicate that O-GlcNAc expression level in prostate cancer cells is associated with poor prognosis of prostate cancer patients and likely enhances tumor cell proliferation and invasion. 24366413 9 24 located observed 1700:1707 arg1 O-GlcNAc 1635:1642 O-GlcNAc 1635:1642 O-GlcNAc 1635:1642 Furthermore, O-GlcNAc was the only item in which a significant difference was observed at overall survival by multivariate analysis (P=0.0475). 24366413 9 24 located observed 1700:1707 arg1 survival 1720:1727 overall survival 1712:1727 overall survival by multivariate analysis (P=0.0475) 1712:1763 Furthermore, O-GlcNAc was the only item in which a significant difference was observed at overall survival by multivariate analysis (P=0.0475). 24366413 9 24 located observed 1700:1707 arg1 item 1657:1660 the only item 1648:1660 the only item in which a significant difference was observed at overall survival by multivariate analysis (P=0.0475) 1648:1763 Furthermore, O-GlcNAc was the only item in which a significant difference was observed at overall survival by multivariate analysis (P=0.0475). 24366413 9 24 located observed 1700:1707 arg2 difference 1685:1694 a significant difference 1671:1694 a significant difference 1671:1694 Furthermore, O-GlcNAc was the only item in which a significant difference was observed at overall survival by multivariate analysis (P=0.0475). 24366413 4 25 theme same 787:790 arg1 sections 792:799 the same sections 783:799 the same sections 783:799 METHODS O-GlcNAc expression level in prostate cancer cells was determined by immunohistochemistry of prostate biopsy specimens obtained from 56 patients later treated with hormone deprivation therapy comparing with adjacent normal prostate glands in the same sections. 24366413 5 26 theme proportional 862:873 arg1 hazards 875:881 the Kaplan-Meier and Cox proportional hazards 837:881 hazards 875:881 Overall survival was determined by the Kaplan-Meier and Cox proportional hazards methods with univariate and multivariate models. 24366413 7 27 theme cytoplasmic 1227:1237 arg1 staining 1239:1246 stronger cytoplasmic staining 1218:1246 stronger cytoplasmic staining than normal prostate glands 1218:1274 RESULTS Defining cancer cells showing stronger cytoplasmic staining than normal prostate glands as overexpression of O-GlcNAc, 39% of prostate cancer patients were categorized as overexpression. 24366413 6 28 theme O-GlcNAc 1102:1109 arg1 OGT 1124:1126 OGT 1124:1126 OGT 1124:1126 The effects of reduced O-GlcNAc expression level on proliferation and invasion of prostate cancer LNCaP cells were examined using small interfering RNA (siRNA) targeting O-GlcNAc transferase (OGT), the enzyme responsible for O-GlcNAc biosynthesis. 24366413 6 28 theme O-GlcNAc 1102:1109 arg1 transferase 1111:1121 O-GlcNAc transferase 1102:1121 O-GlcNAc transferase (OGT) 1102:1127 The effects of reduced O-GlcNAc expression level on proliferation and invasion of prostate cancer LNCaP cells were examined using small interfering RNA (siRNA) targeting O-GlcNAc transferase (OGT), the enzyme responsible for O-GlcNAc biosynthesis. 24366413 6 28 theme O-GlcNAc 1102:1109 arg1 enzyme 1134:1139 the enzyme 1130:1139 the enzyme responsible for O-GlcNAc biosynthesis 1130:1177 The effects of reduced O-GlcNAc expression level on proliferation and invasion of prostate cancer LNCaP cells were examined using small interfering RNA (siRNA) targeting O-GlcNAc transferase (OGT), the enzyme responsible for O-GlcNAc biosynthesis. 24366413 4 29 theme prostate 570:577 arg1 cells 586:590 prostate cancer cells 570:590 prostate cancer cells 570:590 METHODS O-GlcNAc expression level in prostate cancer cells was determined by immunohistochemistry of prostate biopsy specimens obtained from 56 patients later treated with hormone deprivation therapy comparing with adjacent normal prostate glands in the same sections. 24366413 7 30 theme cancer 1323:1328 arg1 patients 1330:1337 prostate cancer patients 1314:1337 prostate cancer patients 1314:1337 RESULTS Defining cancer cells showing stronger cytoplasmic staining than normal prostate glands as overexpression of O-GlcNAc, 39% of prostate cancer patients were categorized as overexpression. 24366413 7 31 theme prostate 1314:1321 arg1 patients 1330:1337 prostate cancer patients 1314:1337 prostate cancer patients 1314:1337 RESULTS Defining cancer cells showing stronger cytoplasmic staining than normal prostate glands as overexpression of O-GlcNAc, 39% of prostate cancer patients were categorized as overexpression. 24366413 3 32 theme O-GlcNAc 487:494 arg1 level 507:511 O-GlcNAc expression level 487:511 O-GlcNAc expression level 487:511 Here we investigated the clinicopathological significance of O-GlcNAc expression level in prostate cancer. 24366413 0 33 theme patients 103:110 arg1 prognosis 90:98 poor prognosis 85:98 poor prognosis of patients 85:110 Overexpression of O-GlcNAc by prostate cancer cells is significantly associated with poor prognosis of patients. 24366413 0 34 theme cancer 39:44 arg1 cells 46:50 prostate cancer cells 30:50 prostate cancer cells 30:50 Overexpression of O-GlcNAc by prostate cancer cells is significantly associated with poor prognosis of patients. 24366413 8 35 dep Kaplan-Meier 1379:1390 arg1 The 1375:1377 The 1375:1377 The 1375:1377 The Kaplan-Meier and Cox proportional hazards methods with univariate model analysis revealed that O-GlcNAc overexpression was associated with overall survival (P=0.0012 for the Kaplan-Meier and P=0.0021 for Cox univariate hazard model analysis). 24366413 8 35 dep Kaplan-Meier 1379:1390 arg1 methods 1421:1427 methods 1421:1427 methods 1421:1427 The Kaplan-Meier and Cox proportional hazards methods with univariate model analysis revealed that O-GlcNAc overexpression was associated with overall survival (P=0.0012 for the Kaplan-Meier and P=0.0021 for Cox univariate hazard model analysis). 24366413 4 36 theme O-GlcNAc 541:548 arg1 level 561:565 METHODS O-GlcNAc expression level 533:565 METHODS O-GlcNAc expression level in prostate cancer cells 533:590 METHODS O-GlcNAc expression level in prostate cancer cells was determined by immunohistochemistry of prostate biopsy specimens obtained from 56 patients later treated with hormone deprivation therapy comparing with adjacent normal prostate glands in the same sections. 24366413 8 37 theme overall 1518:1524 arg1 survival 1526:1533 overall survival 1518:1533 overall survival (P=0.0012 for the Kaplan-Meier and P=0.0021 for Cox univariate hazard model analysis) 1518:1619 The Kaplan-Meier and Cox proportional hazards methods with univariate model analysis revealed that O-GlcNAc overexpression was associated with overall survival (P=0.0012 for the Kaplan-Meier and P=0.0021 for Cox univariate hazard model analysis). 24366413 10 38 theme OGT 1790:1792 arg1 knockdown 1794:1802 siRNA-mediated OGT knockdown 1775:1802 siRNA-mediated OGT knockdown in LNCaP cells 1775:1817 Finally, siRNA-mediated OGT knockdown in LNCaP cells resulted in decreased expression of O-GlcNAc and promoted decreased proliferation and tumor cell invasion compared with control siRNA-transfected LNCaP cells. 24366413 5 39 theme multivariate 911:922 arg1 models 924:929 univariate and multivariate models 896:929 univariate and multivariate models 896:929 Overall survival was determined by the Kaplan-Meier and Cox proportional hazards methods with univariate and multivariate models. 24366413 1 40 theme protein-protein 299:313 arg1 interactions 315:326 protein-protein interactions 299:326 protein-protein interactions 299:326 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) is a glycan essential for fundamental cellular processes such as transcription/translation, nuclear transport, protein stability and protein-protein interactions. 24366413 9 41 theme overall 1712:1718 arg1 survival 1720:1727 overall survival 1712:1727 overall survival by multivariate analysis (P=0.0475) 1712:1763 Furthermore, O-GlcNAc was the only item in which a significant difference was observed at overall survival by multivariate analysis (P=0.0475). 24366413 6 42 theme O-GlcNAc 1157:1164 arg1 biosynthesis 1166:1177 O-GlcNAc biosynthesis 1157:1177 O-GlcNAc biosynthesis 1157:1177 The effects of reduced O-GlcNAc expression level on proliferation and invasion of prostate cancer LNCaP cells were examined using small interfering RNA (siRNA) targeting O-GlcNAc transferase (OGT), the enzyme responsible for O-GlcNAc biosynthesis. 24366413 3 43 theme prostate 516:523 arg1 cancer 525:530 prostate cancer 516:530 prostate cancer 516:530 Here we investigated the clinicopathological significance of O-GlcNAc expression level in prostate cancer. 24366413 0 44 theme O-GlcNAc 18:25 arg1 Overexpression 0:13 Overexpression 0:13 Overexpression of O-GlcNAc by prostate cancer cells 0:50 Overexpression of O-GlcNAc by prostate cancer cells is significantly associated with poor prognosis of patients. 24366413 6 45 theme responsible 1141:1151 arg1 transferase 1111:1121 O-GlcNAc transferase 1102:1121 O-GlcNAc transferase (OGT) 1102:1127 The effects of reduced O-GlcNAc expression level on proliferation and invasion of prostate cancer LNCaP cells were examined using small interfering RNA (siRNA) targeting O-GlcNAc transferase (OGT), the enzyme responsible for O-GlcNAc biosynthesis. 24366413 6 45 theme responsible 1141:1151 arg1 enzyme 1134:1139 the enzyme 1130:1139 the enzyme responsible for O-GlcNAc biosynthesis 1130:1177 The effects of reduced O-GlcNAc expression level on proliferation and invasion of prostate cancer LNCaP cells were examined using small interfering RNA (siRNA) targeting O-GlcNAc transferase (OGT), the enzyme responsible for O-GlcNAc biosynthesis. 24366413 4 46 theme prostate 634:641 arg1 specimens 650:658 prostate biopsy specimens 634:658 prostate biopsy specimens obtained from 56 patients later treated with hormone deprivation therapy comparing with adjacent normal prostate glands in the same sections 634:799 METHODS O-GlcNAc expression level in prostate cancer cells was determined by immunohistochemistry of prostate biopsy specimens obtained from 56 patients later treated with hormone deprivation therapy comparing with adjacent normal prostate glands in the same sections. 24366413 3 47 theme level 507:511 arg1 significance 471:482 the clinicopathological significance 447:482 the clinicopathological significance of O-GlcNAc expression level in prostate cancer 447:530 Here we investigated the clinicopathological significance of O-GlcNAc expression level in prostate cancer. 24366413 0 48 theme prostate 30:37 arg1 cells 46:50 prostate cancer cells 30:50 prostate cancer cells 30:50 Overexpression of O-GlcNAc by prostate cancer cells is significantly associated with poor prognosis of patients. 24366413 6 49 theme expression 964:973 arg1 level 975:979 reduced O-GlcNAc expression level 947:979 reduced O-GlcNAc expression level 947:979 The effects of reduced O-GlcNAc expression level on proliferation and invasion of prostate cancer LNCaP cells were examined using small interfering RNA (siRNA) targeting O-GlcNAc transferase (OGT), the enzyme responsible for O-GlcNAc biosynthesis. 24366413 8 50 with hazards 1413:1419 arg1 analysis 1451:1458 univariate model analysis 1434:1458 univariate model analysis 1434:1458 The Kaplan-Meier and Cox proportional hazards methods with univariate model analysis revealed that O-GlcNAc overexpression was associated with overall survival (P=0.0012 for the Kaplan-Meier and P=0.0021 for Cox univariate hazard model analysis). 24366413 2 51 theme cancer 371:376 arg1 progression 378:388 prostate cancer progression 362:388 prostate cancer progression of patients 362:400 However, the role of O-GlcNAc in prostate cancer progression of patients remains poorly unknown. 24366413 5 52 theme univariate 896:905 arg1 models 924:929 univariate and multivariate models 896:929 univariate and multivariate models 896:929 Overall survival was determined by the Kaplan-Meier and Cox proportional hazards methods with univariate and multivariate models. 24366413 6 53 theme reduced 947:953 arg1 level 975:979 reduced O-GlcNAc expression level 947:979 reduced O-GlcNAc expression level 947:979 The effects of reduced O-GlcNAc expression level on proliferation and invasion of prostate cancer LNCaP cells were examined using small interfering RNA (siRNA) targeting O-GlcNAc transferase (OGT), the enzyme responsible for O-GlcNAc biosynthesis. 24366413 8 54 theme P=0.0021 1570:1577 arg1 analysis 1611:1618 the Kaplan-Meier and P=0.0021 for Cox univariate hazard model analysis 1549:1618 analysis 1611:1618 The Kaplan-Meier and Cox proportional hazards methods with univariate model analysis revealed that O-GlcNAc overexpression was associated with overall survival (P=0.0012 for the Kaplan-Meier and P=0.0021 for Cox univariate hazard model analysis). 24366413 11 55 theme O-GlcNAc 2018:2025 arg1 level 2038:2042 O-GlcNAc expression level 2018:2042 O-GlcNAc expression level in prostate cancer cells 2018:2067 CONCLUSIONS These results indicate that O-GlcNAc expression level in prostate cancer cells is associated with poor prognosis of prostate cancer patients and likely enhances tumor cell proliferation and invasion. 24366413 11 56 theme prostate 2106:2113 arg1 patients 2122:2129 prostate cancer patients 2106:2129 prostate cancer patients 2106:2129 CONCLUSIONS These results indicate that O-GlcNAc expression level in prostate cancer cells is associated with poor prognosis of prostate cancer patients and likely enhances tumor cell proliferation and invasion. 24366413 8 57 theme Cox 1583:1585 arg1 analysis 1611:1618 the Kaplan-Meier and P=0.0021 for Cox univariate hazard model analysis 1549:1618 analysis 1611:1618 The Kaplan-Meier and Cox proportional hazards methods with univariate model analysis revealed that O-GlcNAc overexpression was associated with overall survival (P=0.0012 for the Kaplan-Meier and P=0.0021 for Cox univariate hazard model analysis). 24366413 8 58 dep survival 1526:1533 arg1 P=0.0012 1536:1543 P=0.0012 1536:1543 P=0.0012 1536:1543 The Kaplan-Meier and Cox proportional hazards methods with univariate model analysis revealed that O-GlcNAc overexpression was associated with overall survival (P=0.0012 for the Kaplan-Meier and P=0.0021 for Cox univariate hazard model analysis). 24366413 1 59 theme nuclear 258:264 arg1 transport 266:274 nuclear transport 258:274 nuclear transport 258:274 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) is a glycan essential for fundamental cellular processes such as transcription/translation, nuclear transport, protein stability and protein-protein interactions. 24366413 6 60 theme cells 1036:1040 arg1 invasion 1002:1009 invasion 1002:1009 invasion 1002:1009 The effects of reduced O-GlcNAc expression level on proliferation and invasion of prostate cancer LNCaP cells were examined using small interfering RNA (siRNA) targeting O-GlcNAc transferase (OGT), the enzyme responsible for O-GlcNAc biosynthesis. 24366413 6 60 theme cells 1036:1040 arg1 proliferation 984:996 proliferation 984:996 proliferation 984:996 The effects of reduced O-GlcNAc expression level on proliferation and invasion of prostate cancer LNCaP cells were examined using small interfering RNA (siRNA) targeting O-GlcNAc transferase (OGT), the enzyme responsible for O-GlcNAc biosynthesis. 24366413 5 61 theme Cox 858:860 arg1 hazards 875:881 the Kaplan-Meier and Cox proportional hazards 837:881 hazards 875:881 Overall survival was determined by the Kaplan-Meier and Cox proportional hazards methods with univariate and multivariate models. 24366413 8 62 with Kaplan-Meier 1379:1390 arg1 analysis 1451:1458 univariate model analysis 1434:1458 univariate model analysis 1434:1458 The Kaplan-Meier and Cox proportional hazards methods with univariate model analysis revealed that O-GlcNAc overexpression was associated with overall survival (P=0.0012 for the Kaplan-Meier and P=0.0021 for Cox univariate hazard model analysis). 24366413 11 63 theme prostate 2047:2054 arg1 cells 2063:2067 prostate cancer cells 2047:2067 prostate cancer cells 2047:2067 CONCLUSIONS These results indicate that O-GlcNAc expression level in prostate cancer cells is associated with poor prognosis of prostate cancer patients and likely enhances tumor cell proliferation and invasion. 24366413 6 64 theme cancer 1023:1028 arg1 cells 1036:1040 prostate cancer LNCaP cells 1014:1040 prostate cancer LNCaP cells 1014:1040 The effects of reduced O-GlcNAc expression level on proliferation and invasion of prostate cancer LNCaP cells were examined using small interfering RNA (siRNA) targeting O-GlcNAc transferase (OGT), the enzyme responsible for O-GlcNAc biosynthesis. 24366413 4 65 theme specimens 650:658 arg1 immunohistochemistry 610:629 immunohistochemistry 610:629 immunohistochemistry of prostate biopsy specimens obtained from 56 patients later treated with hormone deprivation therapy comparing with adjacent normal prostate glands in the same sections 610:799 METHODS O-GlcNAc expression level in prostate cancer cells was determined by immunohistochemistry of prostate biopsy specimens obtained from 56 patients later treated with hormone deprivation therapy comparing with adjacent normal prostate glands in the same sections. 24366413 7 66 theme stronger 1218:1225 arg1 staining 1239:1246 stronger cytoplasmic staining 1218:1246 stronger cytoplasmic staining than normal prostate glands 1218:1274 RESULTS Defining cancer cells showing stronger cytoplasmic staining than normal prostate glands as overexpression of O-GlcNAc, 39% of prostate cancer patients were categorized as overexpression. 24366413 4 67 from glands 773:778 arg1 sections 792:799 the same sections 783:799 the same sections 783:799 METHODS O-GlcNAc expression level in prostate cancer cells was determined by immunohistochemistry of prostate biopsy specimens obtained from 56 patients later treated with hormone deprivation therapy comparing with adjacent normal prostate glands in the same sections. 24366413 11 68 theme expression 2027:2036 arg1 level 2038:2042 O-GlcNAc expression level 2018:2042 O-GlcNAc expression level in prostate cancer cells 2018:2067 CONCLUSIONS These results indicate that O-GlcNAc expression level in prostate cancer cells is associated with poor prognosis of prostate cancer patients and likely enhances tumor cell proliferation and invasion. 24366413 10 69 theme O-GlcNAc 1855:1862 arg1 expression 1841:1850 decreased expression 1831:1850 decreased expression of O-GlcNAc 1831:1862 Finally, siRNA-mediated OGT knockdown in LNCaP cells resulted in decreased expression of O-GlcNAc and promoted decreased proliferation and tumor cell invasion compared with control siRNA-transfected LNCaP cells. 24366413 10 70 theme tumor 1905:1909 arg1 invasion 1916:1923 tumor cell invasion 1905:1923 tumor cell invasion 1905:1923 Finally, siRNA-mediated OGT knockdown in LNCaP cells resulted in decreased expression of O-GlcNAc and promoted decreased proliferation and tumor cell invasion compared with control siRNA-transfected LNCaP cells. 24366413 7 71 theme prostate 1260:1267 arg1 glands 1269:1274 normal prostate glands 1253:1274 normal prostate glands 1253:1274 RESULTS Defining cancer cells showing stronger cytoplasmic staining than normal prostate glands as overexpression of O-GlcNAc, 39% of prostate cancer patients were categorized as overexpression. 24366413 5 72 with methods 883:889 arg1 models 924:929 univariate and multivariate models 896:929 univariate and multivariate models 896:929 Overall survival was determined by the Kaplan-Meier and Cox proportional hazards methods with univariate and multivariate models. 24366413 7 73 theme patients 1330:1337 arg1 patients 1330:1337 prostate cancer patients 1314:1337 prostate cancer patients 1314:1337 RESULTS Defining cancer cells showing stronger cytoplasmic staining than normal prostate glands as overexpression of O-GlcNAc, 39% of prostate cancer patients were categorized as overexpression. 24366413 7 73 theme patients 1330:1337 arg1 O-GlcNAc 1297:1304 O-GlcNAc 1297:1304 O-GlcNAc 1297:1304 RESULTS Defining cancer cells showing stronger cytoplasmic staining than normal prostate glands as overexpression of O-GlcNAc, 39% of prostate cancer patients were categorized as overexpression. 24366413 7 73 theme patients 1330:1337 arg1 % 1309:1309 39% 1307:1309 39% of prostate cancer patients 1307:1337 RESULTS Defining cancer cells showing stronger cytoplasmic staining than normal prostate glands as overexpression of O-GlcNAc, 39% of prostate cancer patients were categorized as overexpression. 24366413 10 74 theme siRNA-transfected 1947:1963 arg1 cells 1971:1975 control siRNA-transfected LNCaP cells 1939:1975 control siRNA-transfected LNCaP cells 1939:1975 Finally, siRNA-mediated OGT knockdown in LNCaP cells resulted in decreased expression of O-GlcNAc and promoted decreased proliferation and tumor cell invasion compared with control siRNA-transfected LNCaP cells. 24366413 4 75 theme normal 757:762 arg1 glands 773:778 adjacent normal prostate glands 748:778 adjacent normal prostate glands in the same sections 748:799 METHODS O-GlcNAc expression level in prostate cancer cells was determined by immunohistochemistry of prostate biopsy specimens obtained from 56 patients later treated with hormone deprivation therapy comparing with adjacent normal prostate glands in the same sections. 24366413 1 76 theme cellular 204:211 arg1 processes 213:221 fundamental cellular processes 192:221 fundamental cellular processes such as transcription/translation, nuclear transport, protein stability and protein-protein interactions 192:326 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) is a glycan essential for fundamental cellular processes such as transcription/translation, nuclear transport, protein stability and protein-protein interactions. 24366413 1 76 theme cellular 204:211 arg1 transcription/translation 231:255 transcription/translation 231:255 transcription/translation 231:255 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) is a glycan essential for fundamental cellular processes such as transcription/translation, nuclear transport, protein stability and protein-protein interactions. 24366413 1 76 theme cellular 204:211 arg1 transport 266:274 nuclear transport 258:274 nuclear transport 258:274 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) is a glycan essential for fundamental cellular processes such as transcription/translation, nuclear transport, protein stability and protein-protein interactions. 24366413 1 76 theme cellular 204:211 arg1 stability 285:293 protein stability 277:293 protein stability 277:293 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) is a glycan essential for fundamental cellular processes such as transcription/translation, nuclear transport, protein stability and protein-protein interactions. 24366413 1 76 theme cellular 204:211 arg1 interactions 315:326 protein-protein interactions 299:326 protein-protein interactions 299:326 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) is a glycan essential for fundamental cellular processes such as transcription/translation, nuclear transport, protein stability and protein-protein interactions. 24366413 8 77 theme hazard 1598:1603 arg1 analysis 1611:1618 the Kaplan-Meier and P=0.0021 for Cox univariate hazard model analysis 1549:1618 analysis 1611:1618 The Kaplan-Meier and Cox proportional hazards methods with univariate model analysis revealed that O-GlcNAc overexpression was associated with overall survival (P=0.0012 for the Kaplan-Meier and P=0.0021 for Cox univariate hazard model analysis). 24366413 4 78 theme hormone 705:711 arg1 therapy 725:731 hormone deprivation therapy 705:731 hormone deprivation therapy comparing with adjacent normal prostate glands in the same sections 705:799 METHODS O-GlcNAc expression level in prostate cancer cells was determined by immunohistochemistry of prostate biopsy specimens obtained from 56 patients later treated with hormone deprivation therapy comparing with adjacent normal prostate glands in the same sections. 24366413 6 79 from effects 936:942 arg1 invasion 1002:1009 invasion 1002:1009 invasion 1002:1009 The effects of reduced O-GlcNAc expression level on proliferation and invasion of prostate cancer LNCaP cells were examined using small interfering RNA (siRNA) targeting O-GlcNAc transferase (OGT), the enzyme responsible for O-GlcNAc biosynthesis. 24366413 6 79 from effects 936:942 arg1 proliferation 984:996 proliferation 984:996 proliferation 984:996 The effects of reduced O-GlcNAc expression level on proliferation and invasion of prostate cancer LNCaP cells were examined using small interfering RNA (siRNA) targeting O-GlcNAc transferase (OGT), the enzyme responsible for O-GlcNAc biosynthesis. 24366413 5 80 theme Overall 802:808 arg1 survival 810:817 Overall survival 802:817 Overall survival 802:817 Overall survival was determined by the Kaplan-Meier and Cox proportional hazards methods with univariate and multivariate models. 24366413 6 81 theme small 1062:1066 arg1 RNA 1080:1082 small interfering RNA 1062:1082 small interfering RNA (siRNA) targeting O-GlcNAc transferase (OGT), the enzyme responsible for O-GlcNAc biosynthesis 1062:1177 The effects of reduced O-GlcNAc expression level on proliferation and invasion of prostate cancer LNCaP cells were examined using small interfering RNA (siRNA) targeting O-GlcNAc transferase (OGT), the enzyme responsible for O-GlcNAc biosynthesis. 24366413 6 81 theme small 1062:1066 arg1 siRNA 1085:1089 siRNA 1085:1089 siRNA 1085:1089 The effects of reduced O-GlcNAc expression level on proliferation and invasion of prostate cancer LNCaP cells were examined using small interfering RNA (siRNA) targeting O-GlcNAc transferase (OGT), the enzyme responsible for O-GlcNAc biosynthesis. 24366413 8 82 theme Cox 1396:1398 arg1 hazards 1413:1419 Cox proportional hazards 1396:1419 Cox proportional hazards 1396:1419 The Kaplan-Meier and Cox proportional hazards methods with univariate model analysis revealed that O-GlcNAc overexpression was associated with overall survival (P=0.0012 for the Kaplan-Meier and P=0.0021 for Cox univariate hazard model analysis). 24366413 1 83 theme BACKGROUND 113:122 arg1 β-N-acetylglucosamine 133:153 BACKGROUND O-linked β-N-acetylglucosamine 113:153 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) 113:164 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) is a glycan essential for fundamental cellular processes such as transcription/translation, nuclear transport, protein stability and protein-protein interactions. 24366413 1 83 theme BACKGROUND 113:122 arg1 glycan 171:176 a glycan 169:176 a glycan essential for fundamental cellular processes such as transcription/translation, nuclear transport, protein stability and protein-protein interactions 169:326 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) is a glycan essential for fundamental cellular processes such as transcription/translation, nuclear transport, protein stability and protein-protein interactions. 24366413 1 83 theme BACKGROUND 113:122 arg1 O-GlcNAc 156:163 O-GlcNAc 156:163 O-GlcNAc 156:163 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) is a glycan essential for fundamental cellular processes such as transcription/translation, nuclear transport, protein stability and protein-protein interactions. 24366413 10 84 theme decreased 1877:1885 arg1 proliferation 1887:1899 decreased proliferation 1877:1899 decreased proliferation 1877:1899 Finally, siRNA-mediated OGT knockdown in LNCaP cells resulted in decreased expression of O-GlcNAc and promoted decreased proliferation and tumor cell invasion compared with control siRNA-transfected LNCaP cells. 24366413 5 85 theme Kaplan-Meier 841:852 arg1 methods 883:889 the Kaplan-Meier and Cox proportional hazards methods 837:889 the Kaplan-Meier and Cox proportional hazards methods with univariate and multivariate models 837:929 Overall survival was determined by the Kaplan-Meier and Cox proportional hazards methods with univariate and multivariate models. 24366413 11 86 dep cell 2157:2160 arg1 proliferation 2162:2174 proliferation 2162:2174 proliferation 2162:2174 CONCLUSIONS These results indicate that O-GlcNAc expression level in prostate cancer cells is associated with poor prognosis of prostate cancer patients and likely enhances tumor cell proliferation and invasion. 24366413 11 86 dep cell 2157:2160 arg1 invasion 2180:2187 invasion 2180:2187 invasion 2180:2187 CONCLUSIONS These results indicate that O-GlcNAc expression level in prostate cancer cells is associated with poor prognosis of prostate cancer patients and likely enhances tumor cell proliferation and invasion. 24366413 8 87 theme model 1445:1449 arg1 analysis 1451:1458 univariate model analysis 1434:1458 univariate model analysis 1434:1458 The Kaplan-Meier and Cox proportional hazards methods with univariate model analysis revealed that O-GlcNAc overexpression was associated with overall survival (P=0.0012 for the Kaplan-Meier and P=0.0021 for Cox univariate hazard model analysis). 24366413 0 88 theme poor 85:88 arg1 prognosis 90:98 poor prognosis 85:98 poor prognosis of patients 85:110 Overexpression of O-GlcNAc by prostate cancer cells is significantly associated with poor prognosis of patients. 24366413 4 89 theme cancer 579:584 arg1 cells 586:590 prostate cancer cells 570:590 prostate cancer cells 570:590 METHODS O-GlcNAc expression level in prostate cancer cells was determined by immunohistochemistry of prostate biopsy specimens obtained from 56 patients later treated with hormone deprivation therapy comparing with adjacent normal prostate glands in the same sections. 24366413 11 90 dep CONCLUSIONS 1978:1988 arg1 indicate 2004:2011 indicate 2004:2011 indicate that O-GlcNAc expression level in prostate cancer cells is associated with poor prognosis of prostate cancer patients and likely enhances tumor cell proliferation and invasion 2004:2187 CONCLUSIONS These results indicate that O-GlcNAc expression level in prostate cancer cells is associated with poor prognosis of prostate cancer patients and likely enhances tumor cell proliferation and invasion. 24366413 9 91 theme significant 1673:1683 arg1 difference 1685:1694 a significant difference 1671:1694 a significant difference 1671:1694 Furthermore, O-GlcNAc was the only item in which a significant difference was observed at overall survival by multivariate analysis (P=0.0475). 24366413 2 92 from role 342:345 arg1 progression 378:388 prostate cancer progression 362:388 prostate cancer progression of patients 362:400 However, the role of O-GlcNAc in prostate cancer progression of patients remains poorly unknown. 24366413 4 93 theme METHODS 533:539 arg1 level 561:565 METHODS O-GlcNAc expression level 533:565 METHODS O-GlcNAc expression level in prostate cancer cells 533:590 METHODS O-GlcNAc expression level in prostate cancer cells was determined by immunohistochemistry of prostate biopsy specimens obtained from 56 patients later treated with hormone deprivation therapy comparing with adjacent normal prostate glands in the same sections. 24366413 8 94 theme O-GlcNAc 1474:1481 arg1 overexpression 1483:1496 O-GlcNAc overexpression 1474:1496 O-GlcNAc overexpression 1474:1496 The Kaplan-Meier and Cox proportional hazards methods with univariate model analysis revealed that O-GlcNAc overexpression was associated with overall survival (P=0.0012 for the Kaplan-Meier and P=0.0021 for Cox univariate hazard model analysis). 24366413 10 95 theme decreased 1831:1839 arg1 expression 1841:1850 decreased expression 1831:1850 decreased expression of O-GlcNAc 1831:1862 Finally, siRNA-mediated OGT knockdown in LNCaP cells resulted in decreased expression of O-GlcNAc and promoted decreased proliferation and tumor cell invasion compared with control siRNA-transfected LNCaP cells. 24366413 4 96 theme expression 550:559 arg1 level 561:565 METHODS O-GlcNAc expression level 533:565 METHODS O-GlcNAc expression level in prostate cancer cells 533:590 METHODS O-GlcNAc expression level in prostate cancer cells was determined by immunohistochemistry of prostate biopsy specimens obtained from 56 patients later treated with hormone deprivation therapy comparing with adjacent normal prostate glands in the same sections. 24366413 3 97 theme expression 496:505 arg1 level 507:511 O-GlcNAc expression level 487:511 O-GlcNAc expression level 487:511 Here we investigated the clinicopathological significance of O-GlcNAc expression level in prostate cancer. 24366413 7 98 theme O-GlcNAc 1297:1304 arg1 overexpression 1279:1292 overexpression 1279:1292 overexpression of O-GlcNAc, 39% of prostate cancer patients 1279:1337 RESULTS Defining cancer cells showing stronger cytoplasmic staining than normal prostate glands as overexpression of O-GlcNAc, 39% of prostate cancer patients were categorized as overexpression. 24366413 11 99 from level 2038:2042 arg1 cells 2063:2067 prostate cancer cells 2047:2067 prostate cancer cells 2047:2067 CONCLUSIONS These results indicate that O-GlcNAc expression level in prostate cancer cells is associated with poor prognosis of prostate cancer patients and likely enhances tumor cell proliferation and invasion. 24366413 10 100 theme siRNA-mediated 1775:1788 arg1 knockdown 1794:1802 siRNA-mediated OGT knockdown 1775:1802 siRNA-mediated OGT knockdown in LNCaP cells 1775:1817 Finally, siRNA-mediated OGT knockdown in LNCaP cells resulted in decreased expression of O-GlcNAc and promoted decreased proliferation and tumor cell invasion compared with control siRNA-transfected LNCaP cells. 24366413 4 101 theme biopsy 643:648 arg1 specimens 650:658 prostate biopsy specimens 634:658 prostate biopsy specimens obtained from 56 patients later treated with hormone deprivation therapy comparing with adjacent normal prostate glands in the same sections 634:799 METHODS O-GlcNAc expression level in prostate cancer cells was determined by immunohistochemistry of prostate biopsy specimens obtained from 56 patients later treated with hormone deprivation therapy comparing with adjacent normal prostate glands in the same sections. 24366413 11 102 theme patients 2122:2129 arg1 prognosis 2093:2101 poor prognosis 2088:2101 poor prognosis of prostate cancer patients 2088:2129 CONCLUSIONS These results indicate that O-GlcNAc expression level in prostate cancer cells is associated with poor prognosis of prostate cancer patients and likely enhances tumor cell proliferation and invasion. 24366413 5 103 theme hazards 875:881 arg1 methods 883:889 the Kaplan-Meier and Cox proportional hazards methods 837:889 the Kaplan-Meier and Cox proportional hazards methods with univariate and multivariate models 837:929 Overall survival was determined by the Kaplan-Meier and Cox proportional hazards methods with univariate and multivariate models. 24366413 6 104 theme level 975:979 arg1 effects 936:942 The effects 932:942 The effects of reduced O-GlcNAc expression level on proliferation and invasion of prostate cancer LNCaP cells 932:1040 The effects of reduced O-GlcNAc expression level on proliferation and invasion of prostate cancer LNCaP cells were examined using small interfering RNA (siRNA) targeting O-GlcNAc transferase (OGT), the enzyme responsible for O-GlcNAc biosynthesis. 24366413 9 105 theme multivariate 1732:1743 arg1 P=0.0475 1755:1762 P=0.0475 1755:1762 P=0.0475 1755:1762 Furthermore, O-GlcNAc was the only item in which a significant difference was observed at overall survival by multivariate analysis (P=0.0475). 24366413 9 105 theme multivariate 1732:1743 arg1 analysis 1745:1752 multivariate analysis 1732:1752 multivariate analysis (P=0.0475) 1732:1763 Furthermore, O-GlcNAc was the only item in which a significant difference was observed at overall survival by multivariate analysis (P=0.0475). 24366413 3 106 theme clinicopathological 451:469 arg1 significance 471:482 the clinicopathological significance 447:482 the clinicopathological significance of O-GlcNAc expression level in prostate cancer 447:530 Here we investigated the clinicopathological significance of O-GlcNAc expression level in prostate cancer. 24366413 10 107 theme LNCaP 1807:1811 arg1 cells 1813:1817 LNCaP cells 1807:1817 LNCaP cells 1807:1817 Finally, siRNA-mediated OGT knockdown in LNCaP cells resulted in decreased expression of O-GlcNAc and promoted decreased proliferation and tumor cell invasion compared with control siRNA-transfected LNCaP cells. 24366413 7 108 theme normal 1253:1258 arg1 glands 1269:1274 normal prostate glands 1253:1274 normal prostate glands 1253:1274 RESULTS Defining cancer cells showing stronger cytoplasmic staining than normal prostate glands as overexpression of O-GlcNAc, 39% of prostate cancer patients were categorized as overexpression. 24366413 6 109 theme O-GlcNAc 955:962 arg1 level 975:979 reduced O-GlcNAc expression level 947:979 reduced O-GlcNAc expression level 947:979 The effects of reduced O-GlcNAc expression level on proliferation and invasion of prostate cancer LNCaP cells were examined using small interfering RNA (siRNA) targeting O-GlcNAc transferase (OGT), the enzyme responsible for O-GlcNAc biosynthesis. 24366413 2 110 theme prostate 362:369 arg1 progression 378:388 prostate cancer progression 362:388 prostate cancer progression of patients 362:400 However, the role of O-GlcNAc in prostate cancer progression of patients remains poorly unknown. 24366413 10 111 from knockdown 1794:1802 arg1 cells 1813:1817 LNCaP cells 1807:1817 LNCaP cells 1807:1817 Finally, siRNA-mediated OGT knockdown in LNCaP cells resulted in decreased expression of O-GlcNAc and promoted decreased proliferation and tumor cell invasion compared with control siRNA-transfected LNCaP cells. 24366413 1 112 link O-linked 124:131 arg1 β-N-acetylglucosamine 133:153 BACKGROUND O-linked β-N-acetylglucosamine 113:153 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) 113:164 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) is a glycan essential for fundamental cellular processes such as transcription/translation, nuclear transport, protein stability and protein-protein interactions. 24366413 1 112 link O-linked 124:131 arg1 glycan 171:176 a glycan 169:176 a glycan essential for fundamental cellular processes such as transcription/translation, nuclear transport, protein stability and protein-protein interactions 169:326 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) is a glycan essential for fundamental cellular processes such as transcription/translation, nuclear transport, protein stability and protein-protein interactions. 24366413 1 112 link O-linked 124:131 arg1 O-GlcNAc 156:163 O-GlcNAc 156:163 O-GlcNAc 156:163 BACKGROUND O-linked β-N-acetylglucosamine (O-GlcNAc) is a glycan essential for fundamental cellular processes such as transcription/translation, nuclear transport, protein stability and protein-protein interactions. 24366413 3 113 from significance 471:482 arg1 cancer 525:530 prostate cancer 516:530 prostate cancer 516:530 Here we investigated the clinicopathological significance of O-GlcNAc expression level in prostate cancer. 24366413 2 114 theme O-GlcNAc 350:357 arg1 role 342:345 the role 338:345 the role of O-GlcNAc in prostate cancer progression of patients 338:400 However, the role of O-GlcNAc in prostate cancer progression of patients remains poorly unknown. 24366413 8 115 theme for 1579:1581 arg1 analysis 1611:1618 the Kaplan-Meier and P=0.0021 for Cox univariate hazard model analysis 1549:1618 analysis 1611:1618 The Kaplan-Meier and Cox proportional hazards methods with univariate model analysis revealed that O-GlcNAc overexpression was associated with overall survival (P=0.0012 for the Kaplan-Meier and P=0.0021 for Cox univariate hazard model analysis). 24366413 2 116 theme patients 393:400 arg1 progression 378:388 prostate cancer progression 362:388 prostate cancer progression of patients 362:400 However, the role of O-GlcNAc in prostate cancer progression of patients remains poorly unknown. 24366041 4 0 theme O-GlcNAcylation 826:840 arg1 effects 815:821 the effects 811:821 the effects of O-GlcNAcylation on the blood-retinal barrier 811:869 In addition, the effects of O-GlcNAcylation on the blood-retinal barrier were verified in vitro by the inhibition of O-GlcNAcylation. 24366041 3 1 theme glucose 637:643 arg1 conditions 645:654 high glucose conditions 632:654 high glucose conditions 632:654 In the current study, we examined whether hypoxia increases O-GlcNAcylation in retinal vascular cells under high glucose conditions and whether HIF1α activation is consistent with the response to and activation of O-GlcNAcylation in retinal lesions in diabetic retinopathy. 24366041 3 2 from O-GlcNAcylation 584:598 arg1 cells 620:624 retinal vascular cells 603:624 retinal vascular cells 603:624 In the current study, we examined whether hypoxia increases O-GlcNAcylation in retinal vascular cells under high glucose conditions and whether HIF1α activation is consistent with the response to and activation of O-GlcNAcylation in retinal lesions in diabetic retinopathy. 24366041 3 3 theme HIF1α 668:672 arg1 activation 674:683 HIF1α activation 668:683 HIF1α activation 668:683 In the current study, we examined whether hypoxia increases O-GlcNAcylation in retinal vascular cells under high glucose conditions and whether HIF1α activation is consistent with the response to and activation of O-GlcNAcylation in retinal lesions in diabetic retinopathy. 24366041 7 4 from increase 1379:1386 arg1 O-GlcNAcylation 1397:1411 BRVEC O-GlcNAcylation 1391:1411 BRVEC O-GlcNAcylation 1391:1411 The increase in BRVEC O-GlcNAcylation induced by high glucose, as well as by thiamet G [an O-GlcNAcase (OGA) inhibitor] led to a reduction in occludin expression levels in vitro, which was prevented by treatment with OGT siRNA and alloxan. 24366041 8 5 theme retinal 1857:1863 arg1 layer 1865:1869 the same retinal layer 1848:1869 the same retinal layer 1848:1869 In conclusion, the current study demonstrates the relationship between O-GlcNAc glycosylation and hypoxia during diabetic retinopathy and that hyperglycemia induced O2 consumption activates HIF1α and O-GlcNAc modification protein in the same retinal layer. 24366041 8 6 theme O-GlcNAc 1815:1822 arg1 modification 1824:1835 O-GlcNAc modification 1815:1835 O-GlcNAc modification 1815:1835 In conclusion, the current study demonstrates the relationship between O-GlcNAc glycosylation and hypoxia during diabetic retinopathy and that hyperglycemia induced O2 consumption activates HIF1α and O-GlcNAc modification protein in the same retinal layer. 24366041 1 7 theme db/db 210:214 arg1 retinas 222:228 db/db mouse retinas 210:228 db/db mouse retinas 210:228 An increase in O-linked N-acetylglucosamine (O-GlcNAc) protein modifications has been observerd in db/db mouse retinas. 24366041 0 8 from barrier 78:84 arg1 retinopathy 98:108 diabetic retinopathy 89:108 diabetic retinopathy 89:108 O-GlcNAcylation under hypoxic conditions and its effects on the blood-retinal barrier in diabetic retinopathy. 24366041 7 9 theme occludin 1517:1524 arg1 levels 1537:1542 occludin expression levels 1517:1542 occludin expression levels 1517:1542 The increase in BRVEC O-GlcNAcylation induced by high glucose, as well as by thiamet G [an O-GlcNAcase (OGA) inhibitor] led to a reduction in occludin expression levels in vitro, which was prevented by treatment with OGT siRNA and alloxan. 24366041 6 10 theme BRVEC 1177:1181 arg1 O-GlcNAcylation 1183:1197 Hypoxia-induced BRVEC O-GlcNAcylation 1161:1197 Hypoxia-induced BRVEC O-GlcNAcylation 1161:1197 Hypoxia-induced BRVEC O-GlcNAcylation was not observed when the BRVECs were transfected with siRNA targeting O-GlcNAc transferase (OGT) or treated with alloxan (an OGT inhibitor) prior to exposure to high glucose. 24366041 9 11 theme protein 1884:1890 arg1 levels 1914:1919 The reduced protein BRVEC O-GlcNAcylation levels 1872:1919 The reduced protein BRVEC O-GlcNAcylation levels 1872:1919 The reduced protein BRVEC O-GlcNAcylation levels exert protective effects on the blood-retinal barrier and thus represent a potential therapeutic target for the treatment of diabetic retinopathy. 24366041 6 12 theme O-GlcNAc 1270:1277 arg1 OGT 1292:1294 OGT 1292:1294 OGT 1292:1294 Hypoxia-induced BRVEC O-GlcNAcylation was not observed when the BRVECs were transfected with siRNA targeting O-GlcNAc transferase (OGT) or treated with alloxan (an OGT inhibitor) prior to exposure to high glucose. 24366041 6 12 theme O-GlcNAc 1270:1277 arg1 transferase 1279:1289 O-GlcNAc transferase 1270:1289 O-GlcNAc transferase (OGT) 1270:1295 Hypoxia-induced BRVEC O-GlcNAcylation was not observed when the BRVECs were transfected with siRNA targeting O-GlcNAc transferase (OGT) or treated with alloxan (an OGT inhibitor) prior to exposure to high glucose. 24366041 3 13 theme current 531:537 arg1 study 539:543 the current study 527:543 the current study 527:543 In the current study, we examined whether hypoxia increases O-GlcNAcylation in retinal vascular cells under high glucose conditions and whether HIF1α activation is consistent with the response to and activation of O-GlcNAcylation in retinal lesions in diabetic retinopathy. 24366041 7 14 with treatment 1577:1585 arg1 alloxan 1606:1612 alloxan 1606:1612 alloxan 1606:1612 The increase in BRVEC O-GlcNAcylation induced by high glucose, as well as by thiamet G [an O-GlcNAcase (OGA) inhibitor] led to a reduction in occludin expression levels in vitro, which was prevented by treatment with OGT siRNA and alloxan. 24366041 7 14 with treatment 1577:1585 arg1 siRNA 1596:1600 OGT siRNA 1592:1600 OGT siRNA 1592:1600 The increase in BRVEC O-GlcNAcylation induced by high glucose, as well as by thiamet G [an O-GlcNAcase (OGA) inhibitor] led to a reduction in occludin expression levels in vitro, which was prevented by treatment with OGT siRNA and alloxan. 24366041 9 15 theme O-GlcNAcylation 1898:1912 arg1 levels 1914:1919 The reduced protein BRVEC O-GlcNAcylation levels 1872:1919 The reduced protein BRVEC O-GlcNAcylation levels 1872:1919 The reduced protein BRVEC O-GlcNAcylation levels exert protective effects on the blood-retinal barrier and thus represent a potential therapeutic target for the treatment of diabetic retinopathy. 24366041 2 16 theme mouse 271:275 arg1 retina 277:282 the db/db mouse retina 261:282 the db/db mouse retina 261:282 O-GlcNAc-modified proteins in the db/db mouse retina have been shown to be localized in the ganglion cell layer, the inner nuclear layer, the retina pigment epithelium (RPE) layer and the inner plexiform layer, in which hypoxia-inducible factor 1α (HIF1α) has also been shown to be localized. 24366041 1 17 theme N-acetylglucosamine 135:153 arg1 modifications 174:186 O-linked N-acetylglucosamine (O-GlcNAc) protein modifications 126:186 O-linked N-acetylglucosamine (O-GlcNAc) protein modifications 126:186 An increase in O-linked N-acetylglucosamine (O-GlcNAc) protein modifications has been observerd in db/db mouse retinas. 24366041 5 18 theme glucose 1092:1098 arg1 medium 1100:1105 high glucose medium 1087:1105 high glucose medium (glucose 4.5 g/l) 1087:1123 A time-dependent increase in the O-GlcNAcylation in bovine retinal vascular endothelial cells (BRVECs) was observed following incubation of the cells with high glucose medium (glucose 4.5 g/l) under hypoxic (1-3% O2) conditions. 24366041 5 18 theme glucose 1092:1098 arg1 g/l 1120:1122 glucose 4.5 g/l 1108:1122 glucose 4.5 g/l 1108:1122 A time-dependent increase in the O-GlcNAcylation in bovine retinal vascular endothelial cells (BRVECs) was observed following incubation of the cells with high glucose medium (glucose 4.5 g/l) under hypoxic (1-3% O2) conditions. 24366041 0 19 theme hypoxic 22:28 arg1 conditions 30:39 hypoxic conditions 22:39 hypoxic conditions 22:39 O-GlcNAcylation under hypoxic conditions and its effects on the blood-retinal barrier in diabetic retinopathy. 24366041 2 20 theme hypoxia-inducible 451:467 arg1 factor 469:474 hypoxia-inducible factor 1α 451:477 hypoxia-inducible factor 1α (HIF1α) 451:485 O-GlcNAc-modified proteins in the db/db mouse retina have been shown to be localized in the ganglion cell layer, the inner nuclear layer, the retina pigment epithelium (RPE) layer and the inner plexiform layer, in which hypoxia-inducible factor 1α (HIF1α) has also been shown to be localized. 24366041 2 20 theme hypoxia-inducible 451:467 arg1 HIF1α 480:484 HIF1α 480:484 HIF1α 480:484 O-GlcNAc-modified proteins in the db/db mouse retina have been shown to be localized in the ganglion cell layer, the inner nuclear layer, the retina pigment epithelium (RPE) layer and the inner plexiform layer, in which hypoxia-inducible factor 1α (HIF1α) has also been shown to be localized. 24366041 7 21 from reduction 1504:1512 arg1 levels 1537:1542 occludin expression levels 1517:1542 occludin expression levels 1517:1542 The increase in BRVEC O-GlcNAcylation induced by high glucose, as well as by thiamet G [an O-GlcNAcase (OGA) inhibitor] led to a reduction in occludin expression levels in vitro, which was prevented by treatment with OGT siRNA and alloxan. 24366041 1 22 theme protein 166:172 arg1 modifications 174:186 O-linked N-acetylglucosamine (O-GlcNAc) protein modifications 126:186 O-linked N-acetylglucosamine (O-GlcNAc) protein modifications 126:186 An increase in O-linked N-acetylglucosamine (O-GlcNAc) protein modifications has been observerd in db/db mouse retinas. 24366041 3 23 theme diabetic 776:783 arg1 retinopathy 785:795 diabetic retinopathy 776:795 diabetic retinopathy 776:795 In the current study, we examined whether hypoxia increases O-GlcNAcylation in retinal vascular cells under high glucose conditions and whether HIF1α activation is consistent with the response to and activation of O-GlcNAcylation in retinal lesions in diabetic retinopathy. 24366041 0 24 theme diabetic 89:96 arg1 retinopathy 98:108 diabetic retinopathy 89:108 diabetic retinopathy 89:108 O-GlcNAcylation under hypoxic conditions and its effects on the blood-retinal barrier in diabetic retinopathy. 24366041 4 25 from effects 815:821 arg1 barrier 863:869 the blood-retinal barrier 845:869 the blood-retinal barrier 845:869 In addition, the effects of O-GlcNAcylation on the blood-retinal barrier were verified in vitro by the inhibition of O-GlcNAcylation. 24366041 8 26 theme diabetic 1728:1735 arg1 retinopathy 1737:1747 diabetic retinopathy 1728:1747 diabetic retinopathy 1728:1747 In conclusion, the current study demonstrates the relationship between O-GlcNAc glycosylation and hypoxia during diabetic retinopathy and that hyperglycemia induced O2 consumption activates HIF1α and O-GlcNAc modification protein in the same retinal layer. 24366041 5 27 theme time-dependent 934:947 arg1 increase 949:956 A time-dependent increase 932:956 A time-dependent increase in the O-GlcNAcylation in bovine retinal vascular endothelial cells (BRVECs) 932:1033 A time-dependent increase in the O-GlcNAcylation in bovine retinal vascular endothelial cells (BRVECs) was observed following incubation of the cells with high glucose medium (glucose 4.5 g/l) under hypoxic (1-3% O2) conditions. 24366041 0 28 from effects 49:55 arg1 barrier 78:84 the blood-retinal barrier 60:84 the blood-retinal barrier in diabetic retinopathy 60:108 O-GlcNAcylation under hypoxic conditions and its effects on the blood-retinal barrier in diabetic retinopathy. 24366041 2 29 theme pigment 380:386 arg1 RPE 400:402 RPE 400:402 RPE 400:402 O-GlcNAc-modified proteins in the db/db mouse retina have been shown to be localized in the ganglion cell layer, the inner nuclear layer, the retina pigment epithelium (RPE) layer and the inner plexiform layer, in which hypoxia-inducible factor 1α (HIF1α) has also been shown to be localized. 24366041 2 29 theme pigment 380:386 arg1 epithelium 388:397 the retina pigment epithelium 369:397 the retina pigment epithelium (RPE) layer 369:409 O-GlcNAc-modified proteins in the db/db mouse retina have been shown to be localized in the ganglion cell layer, the inner nuclear layer, the retina pigment epithelium (RPE) layer and the inner plexiform layer, in which hypoxia-inducible factor 1α (HIF1α) has also been shown to be localized. 24366041 2 30 theme inner 419:423 arg1 layer 435:439 the inner plexiform layer 415:439 the inner plexiform layer 415:439 O-GlcNAc-modified proteins in the db/db mouse retina have been shown to be localized in the ganglion cell layer, the inner nuclear layer, the retina pigment epithelium (RPE) layer and the inner plexiform layer, in which hypoxia-inducible factor 1α (HIF1α) has also been shown to be localized. 24366041 5 31 theme hypoxic 1131:1137 arg1 conditions 1149:1158 hypoxic (1-3% O2) conditions 1131:1158 hypoxic (1-3% O2) conditions 1131:1158 A time-dependent increase in the O-GlcNAcylation in bovine retinal vascular endothelial cells (BRVECs) was observed following incubation of the cells with high glucose medium (glucose 4.5 g/l) under hypoxic (1-3% O2) conditions. 24366041 1 32 from increase 114:121 arg1 modifications 174:186 O-linked N-acetylglucosamine (O-GlcNAc) protein modifications 126:186 O-linked N-acetylglucosamine (O-GlcNAc) protein modifications 126:186 An increase in O-linked N-acetylglucosamine (O-GlcNAc) protein modifications has been observerd in db/db mouse retinas. 24366041 6 33 theme high 1361:1364 arg1 glucose 1366:1372 high glucose 1361:1372 high glucose 1361:1372 Hypoxia-induced BRVEC O-GlcNAcylation was not observed when the BRVECs were transfected with siRNA targeting O-GlcNAc transferase (OGT) or treated with alloxan (an OGT inhibitor) prior to exposure to high glucose. 24366041 7 34 theme G 1460:1460 arg1 inhibitor 1484:1492 thiamet G [an O-GlcNAcase (OGA) inhibitor 1452:1492 thiamet G [an O-GlcNAcase (OGA) inhibitor 1452:1492 The increase in BRVEC O-GlcNAcylation induced by high glucose, as well as by thiamet G [an O-GlcNAcase (OGA) inhibitor] led to a reduction in occludin expression levels in vitro, which was prevented by treatment with OGT siRNA and alloxan. 24366041 2 35 located localized 306:314 arg1 layer 337:341 the ganglion cell layer 319:341 the ganglion cell layer 319:341 O-GlcNAc-modified proteins in the db/db mouse retina have been shown to be localized in the ganglion cell layer, the inner nuclear layer, the retina pigment epithelium (RPE) layer and the inner plexiform layer, in which hypoxia-inducible factor 1α (HIF1α) has also been shown to be localized. 24366041 2 35 located localized 306:314 arg1 layer 435:439 the inner plexiform layer 415:439 the inner plexiform layer 415:439 O-GlcNAc-modified proteins in the db/db mouse retina have been shown to be localized in the ganglion cell layer, the inner nuclear layer, the retina pigment epithelium (RPE) layer and the inner plexiform layer, in which hypoxia-inducible factor 1α (HIF1α) has also been shown to be localized. 24366041 2 35 located localized 306:314 arg1 layer 405:409 the retina pigment epithelium (RPE) layer 369:409 the retina pigment epithelium (RPE) layer 369:409 O-GlcNAc-modified proteins in the db/db mouse retina have been shown to be localized in the ganglion cell layer, the inner nuclear layer, the retina pigment epithelium (RPE) layer and the inner plexiform layer, in which hypoxia-inducible factor 1α (HIF1α) has also been shown to be localized. 24366041 2 35 located localized 306:314 arg1 layer 362:366 the inner nuclear layer 344:366 the inner nuclear layer 344:366 O-GlcNAc-modified proteins in the db/db mouse retina have been shown to be localized in the ganglion cell layer, the inner nuclear layer, the retina pigment epithelium (RPE) layer and the inner plexiform layer, in which hypoxia-inducible factor 1α (HIF1α) has also been shown to be localized. 24366041 2 35 located localized 306:314 arg2 proteins 249:256 O-GlcNAc-modified proteins 231:256 O-GlcNAc-modified proteins in the db/db mouse retina 231:282 O-GlcNAc-modified proteins in the db/db mouse retina have been shown to be localized in the ganglion cell layer, the inner nuclear layer, the retina pigment epithelium (RPE) layer and the inner plexiform layer, in which hypoxia-inducible factor 1α (HIF1α) has also been shown to be localized. 24366041 3 36 theme retinal 603:609 arg1 cells 620:624 retinal vascular cells 603:624 retinal vascular cells 603:624 In the current study, we examined whether hypoxia increases O-GlcNAcylation in retinal vascular cells under high glucose conditions and whether HIF1α activation is consistent with the response to and activation of O-GlcNAcylation in retinal lesions in diabetic retinopathy. 24366041 5 37 theme vascular 999:1006 arg1 BRVECs 1027:1032 BRVECs 1027:1032 BRVECs 1027:1032 A time-dependent increase in the O-GlcNAcylation in bovine retinal vascular endothelial cells (BRVECs) was observed following incubation of the cells with high glucose medium (glucose 4.5 g/l) under hypoxic (1-3% O2) conditions. 24366041 5 37 theme vascular 999:1006 arg1 cells 1020:1024 bovine retinal vascular endothelial cells 984:1024 bovine retinal vascular endothelial cells (BRVECs) 984:1033 A time-dependent increase in the O-GlcNAcylation in bovine retinal vascular endothelial cells (BRVECs) was observed following incubation of the cells with high glucose medium (glucose 4.5 g/l) under hypoxic (1-3% O2) conditions. 24366041 1 38 link O-linked 126:133 arg1 O-GlcNAc 156:163 O-GlcNAc 156:163 O-GlcNAc 156:163 An increase in O-linked N-acetylglucosamine (O-GlcNAc) protein modifications has been observerd in db/db mouse retinas. 24366041 1 38 link O-linked 126:133 arg1 N-acetylglucosamine 135:153 O-linked N-acetylglucosamine 126:153 O-linked N-acetylglucosamine (O-GlcNAc) protein modifications 126:186 An increase in O-linked N-acetylglucosamine (O-GlcNAc) protein modifications has been observerd in db/db mouse retinas. 24366041 6 39 theme prior 1340:1344 arg1 alloxan 1313:1319 alloxan 1313:1319 alloxan (an OGT inhibitor) prior to exposure to high glucose 1313:1372 Hypoxia-induced BRVEC O-GlcNAcylation was not observed when the BRVECs were transfected with siRNA targeting O-GlcNAc transferase (OGT) or treated with alloxan (an OGT inhibitor) prior to exposure to high glucose. 24366041 6 39 theme prior 1340:1344 arg1 inhibitor 1329:1337 an OGT inhibitor 1322:1337 an OGT inhibitor 1322:1337 Hypoxia-induced BRVEC O-GlcNAcylation was not observed when the BRVECs were transfected with siRNA targeting O-GlcNAc transferase (OGT) or treated with alloxan (an OGT inhibitor) prior to exposure to high glucose. 24366041 8 40 from HIF1α 1805:1809 arg1 layer 1865:1869 the same retinal layer 1848:1869 the same retinal layer 1848:1869 In conclusion, the current study demonstrates the relationship between O-GlcNAc glycosylation and hypoxia during diabetic retinopathy and that hyperglycemia induced O2 consumption activates HIF1α and O-GlcNAc modification protein in the same retinal layer. 24366041 3 41 from lesions 765:771 arg1 retinopathy 785:795 diabetic retinopathy 776:795 diabetic retinopathy 776:795 In the current study, we examined whether hypoxia increases O-GlcNAcylation in retinal vascular cells under high glucose conditions and whether HIF1α activation is consistent with the response to and activation of O-GlcNAcylation in retinal lesions in diabetic retinopathy. 24366041 3 42 theme high 632:635 arg1 conditions 645:654 high glucose conditions 632:654 high glucose conditions 632:654 In the current study, we examined whether hypoxia increases O-GlcNAcylation in retinal vascular cells under high glucose conditions and whether HIF1α activation is consistent with the response to and activation of O-GlcNAcylation in retinal lesions in diabetic retinopathy. 24366041 2 43 theme cell 332:335 arg1 layer 337:341 the ganglion cell layer 319:341 the ganglion cell layer 319:341 O-GlcNAc-modified proteins in the db/db mouse retina have been shown to be localized in the ganglion cell layer, the inner nuclear layer, the retina pigment epithelium (RPE) layer and the inner plexiform layer, in which hypoxia-inducible factor 1α (HIF1α) has also been shown to be localized. 24366041 9 44 theme diabetic 2046:2053 arg1 retinopathy 2055:2065 diabetic retinopathy 2046:2065 diabetic retinopathy 2046:2065 The reduced protein BRVEC O-GlcNAcylation levels exert protective effects on the blood-retinal barrier and thus represent a potential therapeutic target for the treatment of diabetic retinopathy. 24366041 3 45 with consistent 688:697 arg1 response 708:715 the response 704:715 the response to and activation of O-GlcNAcylation in retinal lesions in diabetic retinopathy 704:795 In the current study, we examined whether hypoxia increases O-GlcNAcylation in retinal vascular cells under high glucose conditions and whether HIF1α activation is consistent with the response to and activation of O-GlcNAcylation in retinal lesions in diabetic retinopathy. 24366041 7 46 theme high 1424:1427 arg1 glucose 1429:1435 high glucose 1424:1435 high glucose 1424:1435 The increase in BRVEC O-GlcNAcylation induced by high glucose, as well as by thiamet G [an O-GlcNAcase (OGA) inhibitor] led to a reduction in occludin expression levels in vitro, which was prevented by treatment with OGT siRNA and alloxan. 24366041 5 47 theme bovine 984:989 arg1 BRVECs 1027:1032 BRVECs 1027:1032 BRVECs 1027:1032 A time-dependent increase in the O-GlcNAcylation in bovine retinal vascular endothelial cells (BRVECs) was observed following incubation of the cells with high glucose medium (glucose 4.5 g/l) under hypoxic (1-3% O2) conditions. 24366041 5 47 theme bovine 984:989 arg1 cells 1020:1024 bovine retinal vascular endothelial cells 984:1024 bovine retinal vascular endothelial cells (BRVECs) 984:1033 A time-dependent increase in the O-GlcNAcylation in bovine retinal vascular endothelial cells (BRVECs) was observed following incubation of the cells with high glucose medium (glucose 4.5 g/l) under hypoxic (1-3% O2) conditions. 24366041 2 48 theme inner 348:352 arg1 layer 362:366 the inner nuclear layer 344:366 the inner nuclear layer 344:366 O-GlcNAc-modified proteins in the db/db mouse retina have been shown to be localized in the ganglion cell layer, the inner nuclear layer, the retina pigment epithelium (RPE) layer and the inner plexiform layer, in which hypoxia-inducible factor 1α (HIF1α) has also been shown to be localized. 24366041 7 49 theme BRVEC 1391:1395 arg1 O-GlcNAcylation 1397:1411 BRVEC O-GlcNAcylation 1391:1411 BRVEC O-GlcNAcylation 1391:1411 The increase in BRVEC O-GlcNAcylation induced by high glucose, as well as by thiamet G [an O-GlcNAcase (OGA) inhibitor] led to a reduction in occludin expression levels in vitro, which was prevented by treatment with OGT siRNA and alloxan. 24366041 5 50 from O-GlcNAcylation 965:979 arg1 BRVECs 1027:1032 BRVECs 1027:1032 BRVECs 1027:1032 A time-dependent increase in the O-GlcNAcylation in bovine retinal vascular endothelial cells (BRVECs) was observed following incubation of the cells with high glucose medium (glucose 4.5 g/l) under hypoxic (1-3% O2) conditions. 24366041 5 50 from O-GlcNAcylation 965:979 arg1 cells 1020:1024 bovine retinal vascular endothelial cells 984:1024 bovine retinal vascular endothelial cells (BRVECs) 984:1033 A time-dependent increase in the O-GlcNAcylation in bovine retinal vascular endothelial cells (BRVECs) was observed following incubation of the cells with high glucose medium (glucose 4.5 g/l) under hypoxic (1-3% O2) conditions. 24366041 7 51 theme expression 1526:1535 arg1 levels 1537:1542 occludin expression levels 1517:1542 occludin expression levels 1517:1542 The increase in BRVEC O-GlcNAcylation induced by high glucose, as well as by thiamet G [an O-GlcNAcase (OGA) inhibitor] led to a reduction in occludin expression levels in vitro, which was prevented by treatment with OGT siRNA and alloxan. 24366041 8 52 theme same 1852:1855 arg1 layer 1865:1869 the same retinal layer 1848:1869 the same retinal layer 1848:1869 In conclusion, the current study demonstrates the relationship between O-GlcNAc glycosylation and hypoxia during diabetic retinopathy and that hyperglycemia induced O2 consumption activates HIF1α and O-GlcNAc modification protein in the same retinal layer. 24366041 1 53 theme mouse 216:220 arg1 retinas 222:228 db/db mouse retinas 210:228 db/db mouse retinas 210:228 An increase in O-linked N-acetylglucosamine (O-GlcNAc) protein modifications has been observerd in db/db mouse retinas. 24366041 9 54 theme reduced 1876:1882 arg1 levels 1914:1919 The reduced protein BRVEC O-GlcNAcylation levels 1872:1919 The reduced protein BRVEC O-GlcNAcylation levels 1872:1919 The reduced protein BRVEC O-GlcNAcylation levels exert protective effects on the blood-retinal barrier and thus represent a potential therapeutic target for the treatment of diabetic retinopathy. 24366041 3 55 theme O-GlcNAcylation 738:752 arg1 activation 724:733 and activation 720:733 activation 724:733 In the current study, we examined whether hypoxia increases O-GlcNAcylation in retinal vascular cells under high glucose conditions and whether HIF1α activation is consistent with the response to and activation of O-GlcNAcylation in retinal lesions in diabetic retinopathy. 24366041 2 56 theme O-GlcNAc-modified 231:247 arg1 proteins 249:256 O-GlcNAc-modified proteins 231:256 O-GlcNAc-modified proteins in the db/db mouse retina 231:282 O-GlcNAc-modified proteins in the db/db mouse retina have been shown to be localized in the ganglion cell layer, the inner nuclear layer, the retina pigment epithelium (RPE) layer and the inner plexiform layer, in which hypoxia-inducible factor 1α (HIF1α) has also been shown to be localized. 24366041 8 57 theme current 1634:1640 arg1 study 1642:1646 the current study 1630:1646 the current study 1630:1646 In conclusion, the current study demonstrates the relationship between O-GlcNAc glycosylation and hypoxia during diabetic retinopathy and that hyperglycemia induced O2 consumption activates HIF1α and O-GlcNAc modification protein in the same retinal layer. 24366041 4 58 theme blood-retinal 849:861 arg1 barrier 863:869 the blood-retinal barrier 845:869 the blood-retinal barrier 845:869 In addition, the effects of O-GlcNAcylation on the blood-retinal barrier were verified in vitro by the inhibition of O-GlcNAcylation. 24366041 6 59 theme Hypoxia-induced 1161:1175 arg1 O-GlcNAcylation 1183:1197 Hypoxia-induced BRVEC O-GlcNAcylation 1161:1197 Hypoxia-induced BRVEC O-GlcNAcylation 1161:1197 Hypoxia-induced BRVEC O-GlcNAcylation was not observed when the BRVECs were transfected with siRNA targeting O-GlcNAc transferase (OGT) or treated with alloxan (an OGT inhibitor) prior to exposure to high glucose. 24366041 9 60 theme BRVEC 1892:1896 arg1 levels 1914:1919 The reduced protein BRVEC O-GlcNAcylation levels 1872:1919 The reduced protein BRVEC O-GlcNAcylation levels 1872:1919 The reduced protein BRVEC O-GlcNAcylation levels exert protective effects on the blood-retinal barrier and thus represent a potential therapeutic target for the treatment of diabetic retinopathy. 24366041 1 61 theme O-linked 126:133 arg1 O-GlcNAc 156:163 O-GlcNAc 156:163 O-GlcNAc 156:163 An increase in O-linked N-acetylglucosamine (O-GlcNAc) protein modifications has been observerd in db/db mouse retinas. 24366041 1 61 theme O-linked 126:133 arg1 N-acetylglucosamine 135:153 O-linked N-acetylglucosamine 126:153 O-linked N-acetylglucosamine (O-GlcNAc) protein modifications 126:186 An increase in O-linked N-acetylglucosamine (O-GlcNAc) protein modifications has been observerd in db/db mouse retinas. 24366041 0 62 theme blood-retinal 64:76 arg1 barrier 78:84 the blood-retinal barrier 60:84 the blood-retinal barrier in diabetic retinopathy 60:108 O-GlcNAcylation under hypoxic conditions and its effects on the blood-retinal barrier in diabetic retinopathy. 24366041 2 63 theme db/db 265:269 arg1 retina 277:282 the db/db mouse retina 261:282 the db/db mouse retina 261:282 O-GlcNAc-modified proteins in the db/db mouse retina have been shown to be localized in the ganglion cell layer, the inner nuclear layer, the retina pigment epithelium (RPE) layer and the inner plexiform layer, in which hypoxia-inducible factor 1α (HIF1α) has also been shown to be localized. 24366041 9 64 dep potential 1996:2004 arg1 therapeutic 2006:2016 therapeutic 2006:2016 therapeutic 2006:2016 The reduced protein BRVEC O-GlcNAcylation levels exert protective effects on the blood-retinal barrier and thus represent a potential therapeutic target for the treatment of diabetic retinopathy. 24366041 0 65 from conditions 30:39 arg1 barrier 78:84 the blood-retinal barrier 60:84 the blood-retinal barrier in diabetic retinopathy 60:108 O-GlcNAcylation under hypoxic conditions and its effects on the blood-retinal barrier in diabetic retinopathy. 24366041 9 66 theme protective 1927:1936 arg1 effects 1938:1944 protective effects 1927:1944 protective effects 1927:1944 The reduced protein BRVEC O-GlcNAcylation levels exert protective effects on the blood-retinal barrier and thus represent a potential therapeutic target for the treatment of diabetic retinopathy. 24366041 3 67 theme retinal 757:763 arg1 lesions 765:771 retinal lesions 757:771 retinal lesions in diabetic retinopathy 757:795 In the current study, we examined whether hypoxia increases O-GlcNAcylation in retinal vascular cells under high glucose conditions and whether HIF1α activation is consistent with the response to and activation of O-GlcNAcylation in retinal lesions in diabetic retinopathy. 24366041 6 68 theme OGT 1325:1327 arg1 alloxan 1313:1319 alloxan 1313:1319 alloxan (an OGT inhibitor) prior to exposure to high glucose 1313:1372 Hypoxia-induced BRVEC O-GlcNAcylation was not observed when the BRVECs were transfected with siRNA targeting O-GlcNAc transferase (OGT) or treated with alloxan (an OGT inhibitor) prior to exposure to high glucose. 24366041 6 68 theme OGT 1325:1327 arg1 inhibitor 1329:1337 an OGT inhibitor 1322:1337 an OGT inhibitor 1322:1337 Hypoxia-induced BRVEC O-GlcNAcylation was not observed when the BRVECs were transfected with siRNA targeting O-GlcNAc transferase (OGT) or treated with alloxan (an OGT inhibitor) prior to exposure to high glucose. 24366041 8 69 theme O-GlcNAc 1686:1693 arg1 glycosylation 1695:1707 O-GlcNAc glycosylation 1686:1707 O-GlcNAc glycosylation 1686:1707 In conclusion, the current study demonstrates the relationship between O-GlcNAc glycosylation and hypoxia during diabetic retinopathy and that hyperglycemia induced O2 consumption activates HIF1α and O-GlcNAc modification protein in the same retinal layer. 24366041 7 70 theme OGA 1479:1481 arg1 inhibitor 1484:1492 thiamet G [an O-GlcNAcase (OGA) inhibitor 1452:1492 thiamet G [an O-GlcNAcase (OGA) inhibitor 1452:1492 The increase in BRVEC O-GlcNAcylation induced by high glucose, as well as by thiamet G [an O-GlcNAcase (OGA) inhibitor] led to a reduction in occludin expression levels in vitro, which was prevented by treatment with OGT siRNA and alloxan. 24366041 8 71 dep HIF1α 1805:1809 arg1 protein 1837:1843 protein 1837:1843 protein 1837:1843 In conclusion, the current study demonstrates the relationship between O-GlcNAc glycosylation and hypoxia during diabetic retinopathy and that hyperglycemia induced O2 consumption activates HIF1α and O-GlcNAc modification protein in the same retinal layer. 24366041 5 72 dep hypoxic 1131:1137 arg1 % 1143:1143 1-3% O2 1140:1146 1-3% O2 1140:1146 A time-dependent increase in the O-GlcNAcylation in bovine retinal vascular endothelial cells (BRVECs) was observed following incubation of the cells with high glucose medium (glucose 4.5 g/l) under hypoxic (1-3% O2) conditions. 24366041 3 73 from activation 724:733 arg1 lesions 765:771 retinal lesions 757:771 retinal lesions in diabetic retinopathy 757:795 In the current study, we examined whether hypoxia increases O-GlcNAcylation in retinal vascular cells under high glucose conditions and whether HIF1α activation is consistent with the response to and activation of O-GlcNAcylation in retinal lesions in diabetic retinopathy. 24366041 5 74 theme glucose 1108:1114 arg1 medium 1100:1105 high glucose medium 1087:1105 high glucose medium (glucose 4.5 g/l) 1087:1123 A time-dependent increase in the O-GlcNAcylation in bovine retinal vascular endothelial cells (BRVECs) was observed following incubation of the cells with high glucose medium (glucose 4.5 g/l) under hypoxic (1-3% O2) conditions. 24366041 5 74 theme glucose 1108:1114 arg1 g/l 1120:1122 glucose 4.5 g/l 1108:1122 glucose 4.5 g/l 1108:1122 A time-dependent increase in the O-GlcNAcylation in bovine retinal vascular endothelial cells (BRVECs) was observed following incubation of the cells with high glucose medium (glucose 4.5 g/l) under hypoxic (1-3% O2) conditions. 24366041 7 75 theme O-GlcNAcase 1466:1476 arg1 inhibitor 1484:1492 thiamet G [an O-GlcNAcase (OGA) inhibitor 1452:1492 thiamet G [an O-GlcNAcase (OGA) inhibitor 1452:1492 The increase in BRVEC O-GlcNAcylation induced by high glucose, as well as by thiamet G [an O-GlcNAcase (OGA) inhibitor] led to a reduction in occludin expression levels in vitro, which was prevented by treatment with OGT siRNA and alloxan. 24366041 9 76 theme blood-retinal 1953:1965 arg1 barrier 1967:1973 the blood-retinal barrier 1949:1973 the blood-retinal barrier 1949:1973 The reduced protein BRVEC O-GlcNAcylation levels exert protective effects on the blood-retinal barrier and thus represent a potential therapeutic target for the treatment of diabetic retinopathy. 24366041 5 77 theme cells 1076:1080 arg1 incubation 1058:1067 incubation 1058:1067 incubation of the cells with high glucose medium (glucose 4.5 g/l) 1058:1123 A time-dependent increase in the O-GlcNAcylation in bovine retinal vascular endothelial cells (BRVECs) was observed following incubation of the cells with high glucose medium (glucose 4.5 g/l) under hypoxic (1-3% O2) conditions. 24366041 7 78 theme OGT 1592:1594 arg1 siRNA 1596:1600 OGT siRNA 1592:1600 OGT siRNA 1592:1600 The increase in BRVEC O-GlcNAcylation induced by high glucose, as well as by thiamet G [an O-GlcNAcase (OGA) inhibitor] led to a reduction in occludin expression levels in vitro, which was prevented by treatment with OGT siRNA and alloxan. 24366041 4 79 theme O-GlcNAcylation 915:929 arg1 inhibition 901:910 the inhibition 897:910 the inhibition of O-GlcNAcylation 897:929 In addition, the effects of O-GlcNAcylation on the blood-retinal barrier were verified in vitro by the inhibition of O-GlcNAcylation. 24366041 2 80 theme retina 373:378 arg1 RPE 400:402 RPE 400:402 RPE 400:402 O-GlcNAc-modified proteins in the db/db mouse retina have been shown to be localized in the ganglion cell layer, the inner nuclear layer, the retina pigment epithelium (RPE) layer and the inner plexiform layer, in which hypoxia-inducible factor 1α (HIF1α) has also been shown to be localized. 24366041 2 80 theme retina 373:378 arg1 epithelium 388:397 the retina pigment epithelium 369:397 the retina pigment epithelium (RPE) layer 369:409 O-GlcNAc-modified proteins in the db/db mouse retina have been shown to be localized in the ganglion cell layer, the inner nuclear layer, the retina pigment epithelium (RPE) layer and the inner plexiform layer, in which hypoxia-inducible factor 1α (HIF1α) has also been shown to be localized. 24366041 5 81 theme high 1087:1090 arg1 glucose 1092:1098 high glucose 1087:1098 high glucose medium (glucose 4.5 g/l) 1087:1123 A time-dependent increase in the O-GlcNAcylation in bovine retinal vascular endothelial cells (BRVECs) was observed following incubation of the cells with high glucose medium (glucose 4.5 g/l) under hypoxic (1-3% O2) conditions. 24366041 2 82 from proteins 249:256 arg1 retina 277:282 the db/db mouse retina 261:282 the db/db mouse retina 261:282 O-GlcNAc-modified proteins in the db/db mouse retina have been shown to be localized in the ganglion cell layer, the inner nuclear layer, the retina pigment epithelium (RPE) layer and the inner plexiform layer, in which hypoxia-inducible factor 1α (HIF1α) has also been shown to be localized. 24366041 5 83 with incubation 1058:1067 arg1 medium 1100:1105 high glucose medium 1087:1105 high glucose medium (glucose 4.5 g/l) 1087:1123 A time-dependent increase in the O-GlcNAcylation in bovine retinal vascular endothelial cells (BRVECs) was observed following incubation of the cells with high glucose medium (glucose 4.5 g/l) under hypoxic (1-3% O2) conditions. 24366041 5 83 with incubation 1058:1067 arg1 g/l 1120:1122 glucose 4.5 g/l 1108:1122 glucose 4.5 g/l 1108:1122 A time-dependent increase in the O-GlcNAcylation in bovine retinal vascular endothelial cells (BRVECs) was observed following incubation of the cells with high glucose medium (glucose 4.5 g/l) under hypoxic (1-3% O2) conditions. 24366041 9 84 theme potential 1996:2004 arg1 target 2018:2023 a potential therapeutic target 1994:2023 a potential therapeutic target for the treatment of diabetic retinopathy 1994:2065 The reduced protein BRVEC O-GlcNAcylation levels exert protective effects on the blood-retinal barrier and thus represent a potential therapeutic target for the treatment of diabetic retinopathy. 24366041 7 85 theme [an 1462:1464 arg1 inhibitor 1484:1492 thiamet G [an O-GlcNAcase (OGA) inhibitor 1452:1492 thiamet G [an O-GlcNAcase (OGA) inhibitor 1452:1492 The increase in BRVEC O-GlcNAcylation induced by high glucose, as well as by thiamet G [an O-GlcNAcase (OGA) inhibitor] led to a reduction in occludin expression levels in vitro, which was prevented by treatment with OGT siRNA and alloxan. 24366041 5 86 theme retinal 991:997 arg1 BRVECs 1027:1032 BRVECs 1027:1032 BRVECs 1027:1032 A time-dependent increase in the O-GlcNAcylation in bovine retinal vascular endothelial cells (BRVECs) was observed following incubation of the cells with high glucose medium (glucose 4.5 g/l) under hypoxic (1-3% O2) conditions. 24366041 5 86 theme retinal 991:997 arg1 cells 1020:1024 bovine retinal vascular endothelial cells 984:1024 bovine retinal vascular endothelial cells (BRVECs) 984:1033 A time-dependent increase in the O-GlcNAcylation in bovine retinal vascular endothelial cells (BRVECs) was observed following incubation of the cells with high glucose medium (glucose 4.5 g/l) under hypoxic (1-3% O2) conditions. 24366041 8 87 from modification 1824:1835 arg1 layer 1865:1869 the same retinal layer 1848:1869 the same retinal layer 1848:1869 In conclusion, the current study demonstrates the relationship between O-GlcNAc glycosylation and hypoxia during diabetic retinopathy and that hyperglycemia induced O2 consumption activates HIF1α and O-GlcNAc modification protein in the same retinal layer. 24366041 2 88 theme epithelium 388:397 arg1 layer 405:409 the retina pigment epithelium (RPE) layer 369:409 the retina pigment epithelium (RPE) layer 369:409 O-GlcNAc-modified proteins in the db/db mouse retina have been shown to be localized in the ganglion cell layer, the inner nuclear layer, the retina pigment epithelium (RPE) layer and the inner plexiform layer, in which hypoxia-inducible factor 1α (HIF1α) has also been shown to be localized. 24366041 7 89 theme thiamet 1452:1458 arg1 inhibitor 1484:1492 thiamet G [an O-GlcNAcase (OGA) inhibitor 1452:1492 thiamet G [an O-GlcNAcase (OGA) inhibitor 1452:1492 The increase in BRVEC O-GlcNAcylation induced by high glucose, as well as by thiamet G [an O-GlcNAcase (OGA) inhibitor] led to a reduction in occludin expression levels in vitro, which was prevented by treatment with OGT siRNA and alloxan. 24366041 5 90 theme endothelial 1008:1018 arg1 BRVECs 1027:1032 BRVECs 1027:1032 BRVECs 1027:1032 A time-dependent increase in the O-GlcNAcylation in bovine retinal vascular endothelial cells (BRVECs) was observed following incubation of the cells with high glucose medium (glucose 4.5 g/l) under hypoxic (1-3% O2) conditions. 24366041 5 90 theme endothelial 1008:1018 arg1 cells 1020:1024 bovine retinal vascular endothelial cells 984:1024 bovine retinal vascular endothelial cells (BRVECs) 984:1033 A time-dependent increase in the O-GlcNAcylation in bovine retinal vascular endothelial cells (BRVECs) was observed following incubation of the cells with high glucose medium (glucose 4.5 g/l) under hypoxic (1-3% O2) conditions. 24366041 2 91 theme plexiform 425:433 arg1 layer 435:439 the inner plexiform layer 415:439 the inner plexiform layer 415:439 O-GlcNAc-modified proteins in the db/db mouse retina have been shown to be localized in the ganglion cell layer, the inner nuclear layer, the retina pigment epithelium (RPE) layer and the inner plexiform layer, in which hypoxia-inducible factor 1α (HIF1α) has also been shown to be localized. 24366041 0 92 dep O-GlcNAcylation 0:14 arg1 conditions 30:39 hypoxic conditions 22:39 hypoxic conditions 22:39 O-GlcNAcylation under hypoxic conditions and its effects on the blood-retinal barrier in diabetic retinopathy. 24366041 0 92 dep O-GlcNAcylation 0:14 arg1 effects 49:55 its effects 45:55 its effects on the blood-retinal barrier in diabetic retinopathy 45:108 O-GlcNAcylation under hypoxic conditions and its effects on the blood-retinal barrier in diabetic retinopathy. 24366041 3 93 theme vascular 611:618 arg1 cells 620:624 retinal vascular cells 603:624 retinal vascular cells 603:624 In the current study, we examined whether hypoxia increases O-GlcNAcylation in retinal vascular cells under high glucose conditions and whether HIF1α activation is consistent with the response to and activation of O-GlcNAcylation in retinal lesions in diabetic retinopathy. 24366041 2 94 theme ganglion 323:330 arg1 layer 337:341 the ganglion cell layer 319:341 the ganglion cell layer 319:341 O-GlcNAc-modified proteins in the db/db mouse retina have been shown to be localized in the ganglion cell layer, the inner nuclear layer, the retina pigment epithelium (RPE) layer and the inner plexiform layer, in which hypoxia-inducible factor 1α (HIF1α) has also been shown to be localized. 24366041 9 95 theme retinopathy 2055:2065 arg1 treatment 2033:2041 the treatment 2029:2041 the treatment of diabetic retinopathy 2029:2065 The reduced protein BRVEC O-GlcNAcylation levels exert protective effects on the blood-retinal barrier and thus represent a potential therapeutic target for the treatment of diabetic retinopathy. 24366041 2 96 theme nuclear 354:360 arg1 layer 362:366 the inner nuclear layer 344:366 the inner nuclear layer 344:366 O-GlcNAc-modified proteins in the db/db mouse retina have been shown to be localized in the ganglion cell layer, the inner nuclear layer, the retina pigment epithelium (RPE) layer and the inner plexiform layer, in which hypoxia-inducible factor 1α (HIF1α) has also been shown to be localized. 24366041 5 97 from increase 949:956 arg1 O-GlcNAcylation 965:979 the O-GlcNAcylation 961:979 the O-GlcNAcylation in bovine retinal vascular endothelial cells (BRVECs) 961:1033 A time-dependent increase in the O-GlcNAcylation in bovine retinal vascular endothelial cells (BRVECs) was observed following incubation of the cells with high glucose medium (glucose 4.5 g/l) under hypoxic (1-3% O2) conditions. 27803463 6 0 theme CHO-K1 1162:1167 arg1 cells 1324:1328 the target cells 1313:1328 the target cells 1313:1328 The CHO-K1 cells stably expressing PILRα were transfected with the expression plasmid for firefly luciferase under the T7 promoter, and were designated as the target cells. 27803463 6 0 theme CHO-K1 1162:1167 arg1 cells 1169:1173 The CHO-K1 cells 1158:1173 The CHO-K1 cells stably expressing PILRα 1158:1197 The CHO-K1 cells stably expressing PILRα were transfected with the expression plasmid for firefly luciferase under the T7 promoter, and were designated as the target cells. 27803463 5 1 theme T7 1096:1097 arg1 polymerase 1103:1112 T7 RNA polymerase 1096:1112 T7 RNA polymerase 1096:1112 Chinese hamster ovary (CHO) cells were transfected with expression plasmids for HSV-1 gB, gD, gH, and gL, and T7 RNA polymerase, and were designated as the effector cells. 27803463 8 2 theme O-glycosylated 1527:1540 arg1 peptide 1546:1552 O-glycosylated sTn peptide 1527:1552 O-glycosylated sTn peptide 1527:1552 Importantly, we found that cell-to-cell fusion was specifically inhibited by O-glycosylated sTn peptide in a dose dependent manner. 27803463 3 3 theme glycoprotein 679:690 arg1 B 692:692 the HSV-1 glycoprotein B 669:692 the HSV-1 glycoprotein B 669:692 Recently, we reported that the sialylated O-linked sugar T antigen (sTn) and its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) protein inhibited HSV-1 infection by specifically targeting paired immunoglobulin-like type 2 receptor alpha (PILRα) in vitro. 27803463 9 4 theme antiviral 1793:1801 arg1 strategies 1815:1824 antiviral therapeutic strategies 1793:1824 antiviral therapeutic strategies for HSV-1-associated diseases 1793:1854 Our results suggested that this virus-free cell-based fusion assay system could be a useful and promising approach to identify novel inhibitors of gB-mediated HSV-1 infection, and will aid in the development of antiviral therapeutic strategies for HSV-1-associated diseases. 27803463 6 5 theme target 1317:1322 arg1 cells 1169:1173 The CHO-K1 cells 1158:1173 The CHO-K1 cells stably expressing PILRα 1158:1197 The CHO-K1 cells stably expressing PILRα were transfected with the expression plasmid for firefly luciferase under the T7 promoter, and were designated as the target cells. 27803463 6 5 theme target 1317:1322 arg1 cells 1324:1328 the target cells 1313:1328 the target cells 1313:1328 The CHO-K1 cells stably expressing PILRα were transfected with the expression plasmid for firefly luciferase under the T7 promoter, and were designated as the target cells. 27803463 9 6 theme strategies 1815:1824 arg1 development 1778:1788 the development 1774:1788 the development of antiviral therapeutic strategies for HSV-1-associated diseases 1774:1854 Our results suggested that this virus-free cell-based fusion assay system could be a useful and promising approach to identify novel inhibitors of gB-mediated HSV-1 infection, and will aid in the development of antiviral therapeutic strategies for HSV-1-associated diseases. 27803463 4 7 theme novel 861:865 arg1 inhibitors 867:876 novel inhibitors 861:876 novel inhibitors of gB-mediated HSV-1 infection 861:907 In this study, to further identify novel inhibitors of gB-mediated HSV-1 infection in vitro, we established a cell-based fusion assay for rapid drug screening. 27803463 9 8 theme HSV-1-associated 1830:1845 arg1 diseases 1847:1854 HSV-1-associated diseases 1830:1854 HSV-1-associated diseases 1830:1854 Our results suggested that this virus-free cell-based fusion assay system could be a useful and promising approach to identify novel inhibitors of gB-mediated HSV-1 infection, and will aid in the development of antiviral therapeutic strategies for HSV-1-associated diseases. 27803463 0 9 theme Type 124:127 arg1 Infection 131:139 Glycoprotein B-Mediated Herpes Simplex Virus Type 1 Infection 79:139 Glycoprotein B-Mediated Herpes Simplex Virus Type 1 Infection 79:139 Rapid Screening by Cell-Based Fusion Assay for Identifying Novel Antivirals of Glycoprotein B-Mediated Herpes Simplex Virus Type 1 Infection. 27803463 0 10 theme Infection 131:139 arg1 Antivirals 65:74 Novel Antivirals 59:74 Novel Antivirals of Glycoprotein B-Mediated Herpes Simplex Virus Type 1 Infection 59:139 Rapid Screening by Cell-Based Fusion Assay for Identifying Novel Antivirals of Glycoprotein B-Mediated Herpes Simplex Virus Type 1 Infection. 27803463 3 11 theme T 579:579 arg1 sTn 590:592 sTn 590:592 sTn 590:592 Recently, we reported that the sialylated O-linked sugar T antigen (sTn) and its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) protein inhibited HSV-1 infection by specifically targeting paired immunoglobulin-like type 2 receptor alpha (PILRα) in vitro. 27803463 3 11 theme T 579:579 arg1 antigen 581:587 O-linked sugar T antigen 564:587 O-linked sugar T antigen (sTn) 564:593 Recently, we reported that the sialylated O-linked sugar T antigen (sTn) and its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) protein inhibited HSV-1 infection by specifically targeting paired immunoglobulin-like type 2 receptor alpha (PILRα) in vitro. 27803463 3 12 theme O-linked 564:571 arg1 sTn 590:592 sTn 590:592 sTn 590:592 Recently, we reported that the sialylated O-linked sugar T antigen (sTn) and its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) protein inhibited HSV-1 infection by specifically targeting paired immunoglobulin-like type 2 receptor alpha (PILRα) in vitro. 27803463 3 12 theme O-linked 564:571 arg1 antigen 581:587 O-linked sugar T antigen 564:587 O-linked sugar T antigen (sTn) 564:593 Recently, we reported that the sialylated O-linked sugar T antigen (sTn) and its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) protein inhibited HSV-1 infection by specifically targeting paired immunoglobulin-like type 2 receptor alpha (PILRα) in vitro. 27803463 9 13 theme cell-based 1625:1634 arg1 approach 1688:1695 a useful and promising approach to identify novel inhibitors of gB-mediated HSV-1 infection 1665:1755 a useful and promising approach to identify novel inhibitors of gB-mediated HSV-1 infection 1665:1755 Our results suggested that this virus-free cell-based fusion assay system could be a useful and promising approach to identify novel inhibitors of gB-mediated HSV-1 infection, and will aid in the development of antiviral therapeutic strategies for HSV-1-associated diseases. 27803463 9 13 theme cell-based 1625:1634 arg1 system 1649:1654 this virus-free cell-based fusion assay system 1609:1654 this virus-free cell-based fusion assay system 1609:1654 Our results suggested that this virus-free cell-based fusion assay system could be a useful and promising approach to identify novel inhibitors of gB-mediated HSV-1 infection, and will aid in the development of antiviral therapeutic strategies for HSV-1-associated diseases. 27803463 3 14 theme paired 759:764 arg1 PILRα 809:813 PILRα 809:813 PILRα 809:813 Recently, we reported that the sialylated O-linked sugar T antigen (sTn) and its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) protein inhibited HSV-1 infection by specifically targeting paired immunoglobulin-like type 2 receptor alpha (PILRα) in vitro. 27803463 3 14 theme paired 759:764 arg1 alpha 802:806 paired immunoglobulin-like type 2 receptor alpha 759:806 paired immunoglobulin-like type 2 receptor alpha (PILRα) 759:814 Recently, we reported that the sialylated O-linked sugar T antigen (sTn) and its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) protein inhibited HSV-1 infection by specifically targeting paired immunoglobulin-like type 2 receptor alpha (PILRα) in vitro. 27803463 5 15 theme hamster 994:1000 arg1 CHO 1009:1011 CHO 1009:1011 CHO 1009:1011 Chinese hamster ovary (CHO) cells were transfected with expression plasmids for HSV-1 gB, gD, gH, and gL, and T7 RNA polymerase, and were designated as the effector cells. 27803463 5 15 theme hamster 994:1000 arg1 ovary 1002:1006 Chinese hamster ovary 986:1006 Chinese hamster ovary (CHO) cells 986:1018 Chinese hamster ovary (CHO) cells were transfected with expression plasmids for HSV-1 gB, gD, gH, and gL, and T7 RNA polymerase, and were designated as the effector cells. 27803463 9 16 theme assay 1643:1647 arg1 approach 1688:1695 a useful and promising approach to identify novel inhibitors of gB-mediated HSV-1 infection 1665:1755 a useful and promising approach to identify novel inhibitors of gB-mediated HSV-1 infection 1665:1755 Our results suggested that this virus-free cell-based fusion assay system could be a useful and promising approach to identify novel inhibitors of gB-mediated HSV-1 infection, and will aid in the development of antiviral therapeutic strategies for HSV-1-associated diseases. 27803463 9 16 theme assay 1643:1647 arg1 system 1649:1654 this virus-free cell-based fusion assay system 1609:1654 this virus-free cell-based fusion assay system 1609:1654 Our results suggested that this virus-free cell-based fusion assay system could be a useful and promising approach to identify novel inhibitors of gB-mediated HSV-1 infection, and will aid in the development of antiviral therapeutic strategies for HSV-1-associated diseases. 27803463 6 17 theme T7 1277:1278 arg1 promoter 1280:1287 the T7 promoter 1273:1287 the T7 promoter 1273:1287 The CHO-K1 cells stably expressing PILRα were transfected with the expression plasmid for firefly luciferase under the T7 promoter, and were designated as the target cells. 27803463 9 18 theme novel 1709:1713 arg1 inhibitors 1715:1724 novel inhibitors 1709:1724 novel inhibitors of gB-mediated HSV-1 infection 1709:1755 Our results suggested that this virus-free cell-based fusion assay system could be a useful and promising approach to identify novel inhibitors of gB-mediated HSV-1 infection, and will aid in the development of antiviral therapeutic strategies for HSV-1-associated diseases. 27803463 1 19 theme simplex 149:155 arg1 HSV-1 171:175 HSV-1 171:175 HSV-1 171:175 Herpes simplex virus type 1 (HSV-1) is a causative agent for a variety of diseases. 27803463 1 19 theme simplex 149:155 arg1 agent 193:197 a causative agent 181:197 a causative agent for a variety of diseases 181:223 Herpes simplex virus type 1 (HSV-1) is a causative agent for a variety of diseases. 27803463 1 19 theme simplex 149:155 arg1 type 163:166 Herpes simplex virus type 1 142:168 Herpes simplex virus type 1 (HSV-1) 142:176 Herpes simplex virus type 1 (HSV-1) is a causative agent for a variety of diseases. 27803463 3 20 theme receptor 793:800 arg1 PILRα 809:813 PILRα 809:813 PILRα 809:813 Recently, we reported that the sialylated O-linked sugar T antigen (sTn) and its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) protein inhibited HSV-1 infection by specifically targeting paired immunoglobulin-like type 2 receptor alpha (PILRα) in vitro. 27803463 3 20 theme receptor 793:800 arg1 alpha 802:806 paired immunoglobulin-like type 2 receptor alpha 759:806 paired immunoglobulin-like type 2 receptor alpha (PILRα) 759:814 Recently, we reported that the sialylated O-linked sugar T antigen (sTn) and its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) protein inhibited HSV-1 infection by specifically targeting paired immunoglobulin-like type 2 receptor alpha (PILRα) in vitro. 27803463 5 21 theme HSV-1 1066:1070 arg1 gB 1072:1073 HSV-1 gB 1066:1073 HSV-1 gB 1066:1073 Chinese hamster ovary (CHO) cells were transfected with expression plasmids for HSV-1 gB, gD, gH, and gL, and T7 RNA polymerase, and were designated as the effector cells. 27803463 4 22 theme HSV-1 893:897 arg1 infection 899:907 gB-mediated HSV-1 infection 881:907 gB-mediated HSV-1 infection 881:907 In this study, to further identify novel inhibitors of gB-mediated HSV-1 infection in vitro, we established a cell-based fusion assay for rapid drug screening. 27803463 3 23 theme type 786:789 arg1 PILRα 809:813 PILRα 809:813 PILRα 809:813 Recently, we reported that the sialylated O-linked sugar T antigen (sTn) and its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) protein inhibited HSV-1 infection by specifically targeting paired immunoglobulin-like type 2 receptor alpha (PILRα) in vitro. 27803463 3 23 theme type 786:789 arg1 alpha 802:806 paired immunoglobulin-like type 2 receptor alpha 759:806 paired immunoglobulin-like type 2 receptor alpha (PILRα) 759:814 Recently, we reported that the sialylated O-linked sugar T antigen (sTn) and its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) protein inhibited HSV-1 infection by specifically targeting paired immunoglobulin-like type 2 receptor alpha (PILRα) in vitro. 27803463 0 24 theme B-Mediated 92:101 arg1 Type 124:127 Glycoprotein B-Mediated Herpes Simplex Virus Type 1 79:129 Glycoprotein B-Mediated Herpes Simplex Virus Type 1 Infection 79:139 Rapid Screening by Cell-Based Fusion Assay for Identifying Novel Antivirals of Glycoprotein B-Mediated Herpes Simplex Virus Type 1 Infection. 27803463 0 25 theme Simplex 110:116 arg1 Type 124:127 Glycoprotein B-Mediated Herpes Simplex Virus Type 1 79:129 Glycoprotein B-Mediated Herpes Simplex Virus Type 1 Infection 79:139 Rapid Screening by Cell-Based Fusion Assay for Identifying Novel Antivirals of Glycoprotein B-Mediated Herpes Simplex Virus Type 1 Infection. 27803463 4 26 theme rapid 964:968 arg1 screening 975:983 rapid drug screening 964:983 rapid drug screening 964:983 In this study, to further identify novel inhibitors of gB-mediated HSV-1 infection in vitro, we established a cell-based fusion assay for rapid drug screening. 27803463 2 27 theme clinical 476:483 arg1 issue 485:489 an important clinical issue 463:489 an important clinical issue that requires urgent solution 463:519 Although antiherpetic drugs such as acyclovir have been developed to inhibit virus replication through interaction with DNA kinases, their continuous administration leads to an increase in the frequency of drug-resistant HSV-1, which is an important clinical issue that requires urgent solution. 27803463 2 27 theme clinical 476:483 arg1 increase 403:410 an increase 400:410 an increase 400:410 Although antiherpetic drugs such as acyclovir have been developed to inhibit virus replication through interaction with DNA kinases, their continuous administration leads to an increase in the frequency of drug-resistant HSV-1, which is an important clinical issue that requires urgent solution. 27803463 0 28 theme Rapid 0:4 arg1 Screening 6:14 Rapid Screening 0:14 Rapid Screening by Cell-Based Fusion Assay for Identifying Novel Antivirals of Glycoprotein B-Mediated Herpes Simplex Virus Type 1 Infection. 0:140 Rapid Screening by Cell-Based Fusion Assay for Identifying Novel Antivirals of Glycoprotein B-Mediated Herpes Simplex Virus Type 1 Infection. 27803463 3 29 gly glycoprotein 679:690 arg1 glycoprotein 679:690 the HSV-1 glycoprotein B 669:692 the HSV-1 glycoprotein B 669:692 Recently, we reported that the sialylated O-linked sugar T antigen (sTn) and its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) protein inhibited HSV-1 infection by specifically targeting paired immunoglobulin-like type 2 receptor alpha (PILRα) in vitro. 27803463 4 30 theme cell-based 936:945 arg1 assay 954:958 a cell-based fusion assay 934:958 a cell-based fusion assay for rapid drug screening 934:983 In this study, to further identify novel inhibitors of gB-mediated HSV-1 infection in vitro, we established a cell-based fusion assay for rapid drug screening. 27803463 3 31 theme peptide 612:618 arg1 peptide 647:653 O-glycosylated sTn peptide 628:653 O-glycosylated sTn peptide 628:653 Recently, we reported that the sialylated O-linked sugar T antigen (sTn) and its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) protein inhibited HSV-1 infection by specifically targeting paired immunoglobulin-like type 2 receptor alpha (PILRα) in vitro. 27803463 3 31 theme peptide 612:618 arg1 gB 695:696 gB 695:696 gB 695:696 Recently, we reported that the sialylated O-linked sugar T antigen (sTn) and its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) protein inhibited HSV-1 infection by specifically targeting paired immunoglobulin-like type 2 receptor alpha (PILRα) in vitro. 27803463 3 31 theme peptide 612:618 arg1 region 620:625 its attached peptide region 599:625 its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) 599:697 Recently, we reported that the sialylated O-linked sugar T antigen (sTn) and its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) protein inhibited HSV-1 infection by specifically targeting paired immunoglobulin-like type 2 receptor alpha (PILRα) in vitro. 27803463 0 32 theme Fusion 30:35 arg1 Assay 37:41 Cell-Based Fusion Assay 19:41 Cell-Based Fusion Assay 19:41 Rapid Screening by Cell-Based Fusion Assay for Identifying Novel Antivirals of Glycoprotein B-Mediated Herpes Simplex Virus Type 1 Infection. 27803463 2 33 theme HSV-1 447:451 arg1 frequency 419:427 the frequency 415:427 the frequency of drug-resistant HSV-1 415:451 Although antiherpetic drugs such as acyclovir have been developed to inhibit virus replication through interaction with DNA kinases, their continuous administration leads to an increase in the frequency of drug-resistant HSV-1, which is an important clinical issue that requires urgent solution. 27803463 0 34 theme Novel 59:63 arg1 Antivirals 65:74 Novel Antivirals 59:74 Novel Antivirals of Glycoprotein B-Mediated Herpes Simplex Virus Type 1 Infection 59:139 Rapid Screening by Cell-Based Fusion Assay for Identifying Novel Antivirals of Glycoprotein B-Mediated Herpes Simplex Virus Type 1 Infection. 27803463 2 35 theme drug-resistant 432:445 arg1 HSV-1 447:451 drug-resistant HSV-1 432:451 drug-resistant HSV-1 432:451 Although antiherpetic drugs such as acyclovir have been developed to inhibit virus replication through interaction with DNA kinases, their continuous administration leads to an increase in the frequency of drug-resistant HSV-1, which is an important clinical issue that requires urgent solution. 27803463 9 36 theme infection 1747:1755 arg1 inhibitors 1715:1724 novel inhibitors 1709:1724 novel inhibitors of gB-mediated HSV-1 infection 1709:1755 Our results suggested that this virus-free cell-based fusion assay system could be a useful and promising approach to identify novel inhibitors of gB-mediated HSV-1 infection, and will aid in the development of antiviral therapeutic strategies for HSV-1-associated diseases. 27803463 3 37 theme sTn 643:645 arg1 peptide 647:653 O-glycosylated sTn peptide 628:653 O-glycosylated sTn peptide 628:653 Recently, we reported that the sialylated O-linked sugar T antigen (sTn) and its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) protein inhibited HSV-1 infection by specifically targeting paired immunoglobulin-like type 2 receptor alpha (PILRα) in vitro. 27803463 3 37 theme sTn 643:645 arg1 region 620:625 its attached peptide region 599:625 its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) 599:697 Recently, we reported that the sialylated O-linked sugar T antigen (sTn) and its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) protein inhibited HSV-1 infection by specifically targeting paired immunoglobulin-like type 2 receptor alpha (PILRα) in vitro. 27803463 2 38 theme virus 303:307 arg1 replication 309:319 virus replication 303:319 virus replication 303:319 Although antiherpetic drugs such as acyclovir have been developed to inhibit virus replication through interaction with DNA kinases, their continuous administration leads to an increase in the frequency of drug-resistant HSV-1, which is an important clinical issue that requires urgent solution. 27803463 8 39 theme sTn 1542:1544 arg1 peptide 1546:1552 O-glycosylated sTn peptide 1527:1552 O-glycosylated sTn peptide 1527:1552 Importantly, we found that cell-to-cell fusion was specifically inhibited by O-glycosylated sTn peptide in a dose dependent manner. 27803463 3 40 gly O-glycosylated 628:641 arg1 peptide 647:653 O-glycosylated sTn peptide 628:653 O-glycosylated sTn peptide 628:653 Recently, we reported that the sialylated O-linked sugar T antigen (sTn) and its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) protein inhibited HSV-1 infection by specifically targeting paired immunoglobulin-like type 2 receptor alpha (PILRα) in vitro. 27803463 3 40 gly O-glycosylated 628:641 arg1 region 620:625 its attached peptide region 599:625 its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) 599:697 Recently, we reported that the sialylated O-linked sugar T antigen (sTn) and its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) protein inhibited HSV-1 infection by specifically targeting paired immunoglobulin-like type 2 receptor alpha (PILRα) in vitro. 27803463 9 41 theme gB-mediated 1729:1739 arg1 infection 1747:1755 gB-mediated HSV-1 infection 1729:1755 gB-mediated HSV-1 infection 1729:1755 Our results suggested that this virus-free cell-based fusion assay system could be a useful and promising approach to identify novel inhibitors of gB-mediated HSV-1 infection, and will aid in the development of antiviral therapeutic strategies for HSV-1-associated diseases. 27803463 8 42 gly O-glycosylated 1527:1540 arg1 peptide 1546:1552 O-glycosylated sTn peptide 1527:1552 O-glycosylated sTn peptide 1527:1552 Importantly, we found that cell-to-cell fusion was specifically inhibited by O-glycosylated sTn peptide in a dose dependent manner. 27803463 2 43 from increase 403:410 arg1 frequency 419:427 the frequency 415:427 the frequency of drug-resistant HSV-1 415:451 Although antiherpetic drugs such as acyclovir have been developed to inhibit virus replication through interaction with DNA kinases, their continuous administration leads to an increase in the frequency of drug-resistant HSV-1, which is an important clinical issue that requires urgent solution. 27803463 1 44 theme diseases 216:223 arg1 variety 205:211 a variety 203:211 a variety of diseases 203:223 Herpes simplex virus type 1 (HSV-1) is a causative agent for a variety of diseases. 27803463 1 44 theme diseases 216:223 arg1 diseases 216:223 diseases 216:223 diseases 216:223 Herpes simplex virus type 1 (HSV-1) is a causative agent for a variety of diseases. 27803463 7 45 theme target 1348:1353 arg1 cells 1355:1359 The effector and target cells 1331:1359 cells 1355:1359 The effector and target cells were co-cultured, and luminescence was measured when both cells were successfully fused. 27803463 5 46 theme RNA 1099:1101 arg1 polymerase 1103:1112 T7 RNA polymerase 1096:1112 T7 RNA polymerase 1096:1112 Chinese hamster ovary (CHO) cells were transfected with expression plasmids for HSV-1 gB, gD, gH, and gL, and T7 RNA polymerase, and were designated as the effector cells. 27803463 3 47 attach derived 656:662 arg2 peptide 647:653 O-glycosylated sTn peptide 628:653 O-glycosylated sTn peptide 628:653 Recently, we reported that the sialylated O-linked sugar T antigen (sTn) and its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) protein inhibited HSV-1 infection by specifically targeting paired immunoglobulin-like type 2 receptor alpha (PILRα) in vitro. 27803463 3 47 attach derived 656:662 arg2 region 620:625 its attached peptide region 599:625 its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) 599:697 Recently, we reported that the sialylated O-linked sugar T antigen (sTn) and its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) protein inhibited HSV-1 infection by specifically targeting paired immunoglobulin-like type 2 receptor alpha (PILRα) in vitro. 27803463 3 47 attach derived 656:662 arg2 gB 695:696 gB 695:696 gB 695:696 Recently, we reported that the sialylated O-linked sugar T antigen (sTn) and its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) protein inhibited HSV-1 infection by specifically targeting paired immunoglobulin-like type 2 receptor alpha (PILRα) in vitro. 27803463 3 47 attach derived 656:662 arg1 B 692:692 the HSV-1 glycoprotein B 669:692 the HSV-1 glycoprotein B 669:692 Recently, we reported that the sialylated O-linked sugar T antigen (sTn) and its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) protein inhibited HSV-1 infection by specifically targeting paired immunoglobulin-like type 2 receptor alpha (PILRα) in vitro. 27803463 7 48 theme effector 1335:1342 arg1 cells 1355:1359 The effector and target cells 1331:1359 cells 1355:1359 The effector and target cells were co-cultured, and luminescence was measured when both cells were successfully fused. 27803463 4 49 theme fusion 947:952 arg1 assay 954:958 a cell-based fusion assay 934:958 a cell-based fusion assay for rapid drug screening 934:983 In this study, to further identify novel inhibitors of gB-mediated HSV-1 infection in vitro, we established a cell-based fusion assay for rapid drug screening. 27803463 9 50 theme therapeutic 1803:1813 arg1 strategies 1815:1824 antiviral therapeutic strategies 1793:1824 antiviral therapeutic strategies for HSV-1-associated diseases 1793:1854 Our results suggested that this virus-free cell-based fusion assay system could be a useful and promising approach to identify novel inhibitors of gB-mediated HSV-1 infection, and will aid in the development of antiviral therapeutic strategies for HSV-1-associated diseases. 27803463 3 51 theme HSV-1 673:677 arg1 B 692:692 the HSV-1 glycoprotein B 669:692 the HSV-1 glycoprotein B 669:692 Recently, we reported that the sialylated O-linked sugar T antigen (sTn) and its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) protein inhibited HSV-1 infection by specifically targeting paired immunoglobulin-like type 2 receptor alpha (PILRα) in vitro. 27803463 6 52 theme expression 1225:1234 arg1 plasmid 1236:1242 the expression plasmid 1221:1242 the expression plasmid for firefly luciferase under the T7 promoter 1221:1287 The CHO-K1 cells stably expressing PILRα were transfected with the expression plasmid for firefly luciferase under the T7 promoter, and were designated as the target cells. 27803463 3 53 theme sugar 573:577 arg1 sTn 590:592 sTn 590:592 sTn 590:592 Recently, we reported that the sialylated O-linked sugar T antigen (sTn) and its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) protein inhibited HSV-1 infection by specifically targeting paired immunoglobulin-like type 2 receptor alpha (PILRα) in vitro. 27803463 3 53 theme sugar 573:577 arg1 antigen 581:587 O-linked sugar T antigen 564:587 O-linked sugar T antigen (sTn) 564:593 Recently, we reported that the sialylated O-linked sugar T antigen (sTn) and its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) protein inhibited HSV-1 infection by specifically targeting paired immunoglobulin-like type 2 receptor alpha (PILRα) in vitro. 27803463 1 54 theme causative 183:191 arg1 type 163:166 Herpes simplex virus type 1 142:168 Herpes simplex virus type 1 (HSV-1) 142:176 Herpes simplex virus type 1 (HSV-1) is a causative agent for a variety of diseases. 27803463 1 54 theme causative 183:191 arg1 agent 193:197 a causative agent 181:197 a causative agent for a variety of diseases 181:223 Herpes simplex virus type 1 (HSV-1) is a causative agent for a variety of diseases. 27803463 3 55 gly sialylated 553:562 arg1 protein 699:705 the sialylated O-linked sugar T antigen (sTn) and its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) protein 549:705 the sialylated O-linked sugar T antigen (sTn) and its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) protein 549:705 Recently, we reported that the sialylated O-linked sugar T antigen (sTn) and its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) protein inhibited HSV-1 infection by specifically targeting paired immunoglobulin-like type 2 receptor alpha (PILRα) in vitro. 27803463 2 56 theme urgent 505:510 arg1 solution 512:519 urgent solution 505:519 urgent solution 505:519 Although antiherpetic drugs such as acyclovir have been developed to inhibit virus replication through interaction with DNA kinases, their continuous administration leads to an increase in the frequency of drug-resistant HSV-1, which is an important clinical issue that requires urgent solution. 27803463 3 57 theme sialylated 553:562 arg1 protein 699:705 the sialylated O-linked sugar T antigen (sTn) and its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) protein 549:705 the sialylated O-linked sugar T antigen (sTn) and its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) protein 549:705 Recently, we reported that the sialylated O-linked sugar T antigen (sTn) and its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) protein inhibited HSV-1 infection by specifically targeting paired immunoglobulin-like type 2 receptor alpha (PILRα) in vitro. 27803463 9 58 theme virus-free 1614:1623 arg1 approach 1688:1695 a useful and promising approach to identify novel inhibitors of gB-mediated HSV-1 infection 1665:1755 a useful and promising approach to identify novel inhibitors of gB-mediated HSV-1 infection 1665:1755 Our results suggested that this virus-free cell-based fusion assay system could be a useful and promising approach to identify novel inhibitors of gB-mediated HSV-1 infection, and will aid in the development of antiviral therapeutic strategies for HSV-1-associated diseases. 27803463 9 58 theme virus-free 1614:1623 arg1 system 1649:1654 this virus-free cell-based fusion assay system 1609:1654 this virus-free cell-based fusion assay system 1609:1654 Our results suggested that this virus-free cell-based fusion assay system could be a useful and promising approach to identify novel inhibitors of gB-mediated HSV-1 infection, and will aid in the development of antiviral therapeutic strategies for HSV-1-associated diseases. 27803463 3 59 theme HSV-1 717:721 arg1 infection 723:731 HSV-1 infection 717:731 HSV-1 infection 717:731 Recently, we reported that the sialylated O-linked sugar T antigen (sTn) and its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) protein inhibited HSV-1 infection by specifically targeting paired immunoglobulin-like type 2 receptor alpha (PILRα) in vitro. 27803463 5 60 theme Chinese 986:992 arg1 CHO 1009:1011 CHO 1009:1011 CHO 1009:1011 Chinese hamster ovary (CHO) cells were transfected with expression plasmids for HSV-1 gB, gD, gH, and gL, and T7 RNA polymerase, and were designated as the effector cells. 27803463 5 60 theme Chinese 986:992 arg1 ovary 1002:1006 Chinese hamster ovary 986:1006 Chinese hamster ovary (CHO) cells 986:1018 Chinese hamster ovary (CHO) cells were transfected with expression plasmids for HSV-1 gB, gD, gH, and gL, and T7 RNA polymerase, and were designated as the effector cells. 27803463 2 61 theme antiherpetic 235:246 arg1 drugs 248:252 antiherpetic drugs 235:252 antiherpetic drugs such as acyclovir 235:270 Although antiherpetic drugs such as acyclovir have been developed to inhibit virus replication through interaction with DNA kinases, their continuous administration leads to an increase in the frequency of drug-resistant HSV-1, which is an important clinical issue that requires urgent solution. 27803463 2 61 theme antiherpetic 235:246 arg1 acyclovir 262:270 acyclovir 262:270 acyclovir 262:270 Although antiherpetic drugs such as acyclovir have been developed to inhibit virus replication through interaction with DNA kinases, their continuous administration leads to an increase in the frequency of drug-resistant HSV-1, which is an important clinical issue that requires urgent solution. 27803463 9 62 theme fusion 1636:1641 arg1 approach 1688:1695 a useful and promising approach to identify novel inhibitors of gB-mediated HSV-1 infection 1665:1755 a useful and promising approach to identify novel inhibitors of gB-mediated HSV-1 infection 1665:1755 Our results suggested that this virus-free cell-based fusion assay system could be a useful and promising approach to identify novel inhibitors of gB-mediated HSV-1 infection, and will aid in the development of antiviral therapeutic strategies for HSV-1-associated diseases. 27803463 9 62 theme fusion 1636:1641 arg1 system 1649:1654 this virus-free cell-based fusion assay system 1609:1654 this virus-free cell-based fusion assay system 1609:1654 Our results suggested that this virus-free cell-based fusion assay system could be a useful and promising approach to identify novel inhibitors of gB-mediated HSV-1 infection, and will aid in the development of antiviral therapeutic strategies for HSV-1-associated diseases. 27803463 3 63 theme immunoglobulin-like 766:784 arg1 PILRα 809:813 PILRα 809:813 PILRα 809:813 Recently, we reported that the sialylated O-linked sugar T antigen (sTn) and its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) protein inhibited HSV-1 infection by specifically targeting paired immunoglobulin-like type 2 receptor alpha (PILRα) in vitro. 27803463 3 63 theme immunoglobulin-like 766:784 arg1 alpha 802:806 paired immunoglobulin-like type 2 receptor alpha 759:806 paired immunoglobulin-like type 2 receptor alpha (PILRα) 759:814 Recently, we reported that the sialylated O-linked sugar T antigen (sTn) and its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) protein inhibited HSV-1 infection by specifically targeting paired immunoglobulin-like type 2 receptor alpha (PILRα) in vitro. 27803463 5 64 theme ovary 1002:1006 arg1 cells 1151:1155 the effector cells 1138:1155 the effector cells 1138:1155 Chinese hamster ovary (CHO) cells were transfected with expression plasmids for HSV-1 gB, gD, gH, and gL, and T7 RNA polymerase, and were designated as the effector cells. 27803463 5 64 theme ovary 1002:1006 arg1 cells 1014:1018 Chinese hamster ovary (CHO) cells 986:1018 Chinese hamster ovary (CHO) cells 986:1018 Chinese hamster ovary (CHO) cells were transfected with expression plasmids for HSV-1 gB, gD, gH, and gL, and T7 RNA polymerase, and were designated as the effector cells. 27803463 3 65 theme antigen 581:587 arg1 protein 699:705 the sialylated O-linked sugar T antigen (sTn) and its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) protein 549:705 the sialylated O-linked sugar T antigen (sTn) and its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) protein 549:705 Recently, we reported that the sialylated O-linked sugar T antigen (sTn) and its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) protein inhibited HSV-1 infection by specifically targeting paired immunoglobulin-like type 2 receptor alpha (PILRα) in vitro. 27803463 1 66 theme Herpes 142:147 arg1 HSV-1 171:175 HSV-1 171:175 HSV-1 171:175 Herpes simplex virus type 1 (HSV-1) is a causative agent for a variety of diseases. 27803463 1 66 theme Herpes 142:147 arg1 agent 193:197 a causative agent 181:197 a causative agent for a variety of diseases 181:223 Herpes simplex virus type 1 (HSV-1) is a causative agent for a variety of diseases. 27803463 1 66 theme Herpes 142:147 arg1 type 163:166 Herpes simplex virus type 1 142:168 Herpes simplex virus type 1 (HSV-1) 142:176 Herpes simplex virus type 1 (HSV-1) is a causative agent for a variety of diseases. 27803463 2 67 theme important 466:474 arg1 issue 485:489 an important clinical issue 463:489 an important clinical issue that requires urgent solution 463:519 Although antiherpetic drugs such as acyclovir have been developed to inhibit virus replication through interaction with DNA kinases, their continuous administration leads to an increase in the frequency of drug-resistant HSV-1, which is an important clinical issue that requires urgent solution. 27803463 2 67 theme important 466:474 arg1 increase 403:410 an increase 400:410 an increase 400:410 Although antiherpetic drugs such as acyclovir have been developed to inhibit virus replication through interaction with DNA kinases, their continuous administration leads to an increase in the frequency of drug-resistant HSV-1, which is an important clinical issue that requires urgent solution. 27803463 4 68 theme gB-mediated 881:891 arg1 infection 899:907 gB-mediated HSV-1 infection 881:907 gB-mediated HSV-1 infection 881:907 In this study, to further identify novel inhibitors of gB-mediated HSV-1 infection in vitro, we established a cell-based fusion assay for rapid drug screening. 27803463 1 69 theme virus 157:161 arg1 HSV-1 171:175 HSV-1 171:175 HSV-1 171:175 Herpes simplex virus type 1 (HSV-1) is a causative agent for a variety of diseases. 27803463 1 69 theme virus 157:161 arg1 agent 193:197 a causative agent 181:197 a causative agent for a variety of diseases 181:223 Herpes simplex virus type 1 (HSV-1) is a causative agent for a variety of diseases. 27803463 1 69 theme virus 157:161 arg1 type 163:166 Herpes simplex virus type 1 142:168 Herpes simplex virus type 1 (HSV-1) 142:176 Herpes simplex virus type 1 (HSV-1) is a causative agent for a variety of diseases. 27803463 5 70 theme effector 1142:1149 arg1 cells 1151:1155 the effector cells 1138:1155 the effector cells 1138:1155 Chinese hamster ovary (CHO) cells were transfected with expression plasmids for HSV-1 gB, gD, gH, and gL, and T7 RNA polymerase, and were designated as the effector cells. 27803463 5 70 theme effector 1142:1149 arg1 cells 1014:1018 Chinese hamster ovary (CHO) cells 986:1018 Chinese hamster ovary (CHO) cells 986:1018 Chinese hamster ovary (CHO) cells were transfected with expression plasmids for HSV-1 gB, gD, gH, and gL, and T7 RNA polymerase, and were designated as the effector cells. 27803463 0 71 theme Herpes 103:108 arg1 Type 124:127 Glycoprotein B-Mediated Herpes Simplex Virus Type 1 79:129 Glycoprotein B-Mediated Herpes Simplex Virus Type 1 Infection 79:139 Rapid Screening by Cell-Based Fusion Assay for Identifying Novel Antivirals of Glycoprotein B-Mediated Herpes Simplex Virus Type 1 Infection. 27803463 9 72 theme useful 1667:1672 arg1 approach 1688:1695 a useful and promising approach to identify novel inhibitors of gB-mediated HSV-1 infection 1665:1755 a useful and promising approach to identify novel inhibitors of gB-mediated HSV-1 infection 1665:1755 Our results suggested that this virus-free cell-based fusion assay system could be a useful and promising approach to identify novel inhibitors of gB-mediated HSV-1 infection, and will aid in the development of antiviral therapeutic strategies for HSV-1-associated diseases. 27803463 9 72 theme useful 1667:1672 arg1 system 1649:1654 this virus-free cell-based fusion assay system 1609:1654 this virus-free cell-based fusion assay system 1609:1654 Our results suggested that this virus-free cell-based fusion assay system could be a useful and promising approach to identify novel inhibitors of gB-mediated HSV-1 infection, and will aid in the development of antiviral therapeutic strategies for HSV-1-associated diseases. 27803463 0 73 theme Virus 118:122 arg1 Type 124:127 Glycoprotein B-Mediated Herpes Simplex Virus Type 1 79:129 Glycoprotein B-Mediated Herpes Simplex Virus Type 1 Infection 79:139 Rapid Screening by Cell-Based Fusion Assay for Identifying Novel Antivirals of Glycoprotein B-Mediated Herpes Simplex Virus Type 1 Infection. 27803463 4 74 theme infection 899:907 arg1 inhibitors 867:876 novel inhibitors 861:876 novel inhibitors of gB-mediated HSV-1 infection 861:907 In this study, to further identify novel inhibitors of gB-mediated HSV-1 infection in vitro, we established a cell-based fusion assay for rapid drug screening. 27803463 2 75 theme continuous 365:374 arg1 administration 376:389 their continuous administration 359:389 their continuous administration 359:389 Although antiherpetic drugs such as acyclovir have been developed to inhibit virus replication through interaction with DNA kinases, their continuous administration leads to an increase in the frequency of drug-resistant HSV-1, which is an important clinical issue that requires urgent solution. 27803463 5 76 theme expression 1042:1051 arg1 plasmids 1053:1060 expression plasmids 1042:1060 expression plasmids for HSV-1 gB, gD, gH, and gL, and T7 RNA polymerase 1042:1112 Chinese hamster ovary (CHO) cells were transfected with expression plasmids for HSV-1 gB, gD, gH, and gL, and T7 RNA polymerase, and were designated as the effector cells. 27803463 0 77 theme Cell-Based 19:28 arg1 Assay 37:41 Cell-Based Fusion Assay 19:41 Cell-Based Fusion Assay 19:41 Rapid Screening by Cell-Based Fusion Assay for Identifying Novel Antivirals of Glycoprotein B-Mediated Herpes Simplex Virus Type 1 Infection. 27803463 4 78 theme drug 970:973 arg1 screening 975:983 rapid drug screening 964:983 rapid drug screening 964:983 In this study, to further identify novel inhibitors of gB-mediated HSV-1 infection in vitro, we established a cell-based fusion assay for rapid drug screening. 27803463 3 79 theme attached 603:610 arg1 peptide 647:653 O-glycosylated sTn peptide 628:653 O-glycosylated sTn peptide 628:653 Recently, we reported that the sialylated O-linked sugar T antigen (sTn) and its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) protein inhibited HSV-1 infection by specifically targeting paired immunoglobulin-like type 2 receptor alpha (PILRα) in vitro. 27803463 3 79 theme attached 603:610 arg1 gB 695:696 gB 695:696 gB 695:696 Recently, we reported that the sialylated O-linked sugar T antigen (sTn) and its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) protein inhibited HSV-1 infection by specifically targeting paired immunoglobulin-like type 2 receptor alpha (PILRα) in vitro. 27803463 3 79 theme attached 603:610 arg1 region 620:625 its attached peptide region 599:625 its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) 599:697 Recently, we reported that the sialylated O-linked sugar T antigen (sTn) and its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) protein inhibited HSV-1 infection by specifically targeting paired immunoglobulin-like type 2 receptor alpha (PILRα) in vitro. 27803463 3 80 link O-linked 564:571 arg1 sTn 590:592 sTn 590:592 sTn 590:592 Recently, we reported that the sialylated O-linked sugar T antigen (sTn) and its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) protein inhibited HSV-1 infection by specifically targeting paired immunoglobulin-like type 2 receptor alpha (PILRα) in vitro. 27803463 3 80 link O-linked 564:571 arg1 antigen 581:587 O-linked sugar T antigen 564:587 O-linked sugar T antigen (sTn) 564:593 Recently, we reported that the sialylated O-linked sugar T antigen (sTn) and its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) protein inhibited HSV-1 infection by specifically targeting paired immunoglobulin-like type 2 receptor alpha (PILRα) in vitro. 27803463 9 81 theme promising 1678:1686 arg1 approach 1688:1695 a useful and promising approach to identify novel inhibitors of gB-mediated HSV-1 infection 1665:1755 a useful and promising approach to identify novel inhibitors of gB-mediated HSV-1 infection 1665:1755 Our results suggested that this virus-free cell-based fusion assay system could be a useful and promising approach to identify novel inhibitors of gB-mediated HSV-1 infection, and will aid in the development of antiviral therapeutic strategies for HSV-1-associated diseases. 27803463 9 81 theme promising 1678:1686 arg1 system 1649:1654 this virus-free cell-based fusion assay system 1609:1654 this virus-free cell-based fusion assay system 1609:1654 Our results suggested that this virus-free cell-based fusion assay system could be a useful and promising approach to identify novel inhibitors of gB-mediated HSV-1 infection, and will aid in the development of antiviral therapeutic strategies for HSV-1-associated diseases. 27803463 9 82 theme HSV-1 1741:1745 arg1 infection 1747:1755 gB-mediated HSV-1 infection 1729:1755 gB-mediated HSV-1 infection 1729:1755 Our results suggested that this virus-free cell-based fusion assay system could be a useful and promising approach to identify novel inhibitors of gB-mediated HSV-1 infection, and will aid in the development of antiviral therapeutic strategies for HSV-1-associated diseases. 27803463 3 83 theme O-glycosylated 628:641 arg1 peptide 647:653 O-glycosylated sTn peptide 628:653 O-glycosylated sTn peptide 628:653 Recently, we reported that the sialylated O-linked sugar T antigen (sTn) and its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) protein inhibited HSV-1 infection by specifically targeting paired immunoglobulin-like type 2 receptor alpha (PILRα) in vitro. 27803463 3 83 theme O-glycosylated 628:641 arg1 region 620:625 its attached peptide region 599:625 its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) 599:697 Recently, we reported that the sialylated O-linked sugar T antigen (sTn) and its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) protein inhibited HSV-1 infection by specifically targeting paired immunoglobulin-like type 2 receptor alpha (PILRα) in vitro. 27803463 2 84 with interaction 329:339 arg1 kinases 350:356 DNA kinases 346:356 DNA kinases 346:356 Although antiherpetic drugs such as acyclovir have been developed to inhibit virus replication through interaction with DNA kinases, their continuous administration leads to an increase in the frequency of drug-resistant HSV-1, which is an important clinical issue that requires urgent solution. 27803463 8 85 theme cell-to-cell 1477:1488 arg1 fusion 1490:1495 cell-to-cell fusion 1477:1495 cell-to-cell fusion 1477:1495 Importantly, we found that cell-to-cell fusion was specifically inhibited by O-glycosylated sTn peptide in a dose dependent manner. 27803463 3 86 theme region 620:625 arg1 protein 699:705 the sialylated O-linked sugar T antigen (sTn) and its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) protein 549:705 the sialylated O-linked sugar T antigen (sTn) and its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) protein 549:705 Recently, we reported that the sialylated O-linked sugar T antigen (sTn) and its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) protein inhibited HSV-1 infection by specifically targeting paired immunoglobulin-like type 2 receptor alpha (PILRα) in vitro. 27803463 6 87 theme firefly 1248:1254 arg1 luciferase 1256:1265 firefly luciferase 1248:1265 firefly luciferase 1248:1265 The CHO-K1 cells stably expressing PILRα were transfected with the expression plasmid for firefly luciferase under the T7 promoter, and were designated as the target cells. 27803463 2 88 theme DNA 346:348 arg1 kinases 350:356 DNA kinases 346:356 DNA kinases 346:356 Although antiherpetic drugs such as acyclovir have been developed to inhibit virus replication through interaction with DNA kinases, their continuous administration leads to an increase in the frequency of drug-resistant HSV-1, which is an important clinical issue that requires urgent solution. 27803463 8 89 theme dependent 1564:1572 arg1 manner 1574:1579 a dose dependent manner 1557:1579 a dose dependent manner 1557:1579 Importantly, we found that cell-to-cell fusion was specifically inhibited by O-glycosylated sTn peptide in a dose dependent manner. 27542280 6 0 theme other 916:920 arg1 factors 930:936 other soluble factors 916:936 other soluble factors 916:936 Similarly, the conditioned media obtained from LPS-stimulated monocytes also elevated Tn levels in primary human gingival fibroblasts, suggesting the involvement of cytokines and/or other soluble factors. 27542280 4 1 theme regulatory 553:562 arg1 molecules 564:572 the common regulatory molecules 542:572 the common regulatory molecules 542:572 In the current studies, we have explored the possibility that cytokines may be one of the common regulatory molecules for elevated Tn levels in both cancer and inflammation. 27542280 2 2 theme inflammatory 338:349 arg1 tissues 351:357 inflammatory tissues 338:357 inflammatory tissues 338:357 There are also reports that Tn is elevated in inflammatory tissues. 27542280 4 3 theme common 546:551 arg1 molecules 564:572 the common regulatory molecules 542:572 the common regulatory molecules 542:572 In the current studies, we have explored the possibility that cytokines may be one of the common regulatory molecules for elevated Tn levels in both cancer and inflammation. 27542280 8 4 theme mRNA 1155:1158 arg1 levels 1135:1140 reduced levels 1127:1140 reduced levels of the COSMC mRNA and protein 1127:1170 Furthermore, TNF-α was shown to down-regulate the COSMC gene as evidenced by reduced levels of the COSMC mRNA and protein, as well as hypermethylation of the CpG islands of the COSMC gene promoter. 27542280 8 4 theme mRNA 1155:1158 arg1 hypermethylation 1184:1199 hypermethylation 1184:1199 hypermethylation of the CpG islands of the COSMC gene promoter 1184:1245 Furthermore, TNF-α was shown to down-regulate the COSMC gene as evidenced by reduced levels of the COSMC mRNA and protein, as well as hypermethylation of the CpG islands of the COSMC gene promoter. 27542280 6 5 theme cytokines 899:907 arg1 involvement 884:894 the involvement 880:894 the involvement of cytokines and/or other soluble factors 880:936 Similarly, the conditioned media obtained from LPS-stimulated monocytes also elevated Tn levels in primary human gingival fibroblasts, suggesting the involvement of cytokines and/or other soluble factors. 27542280 8 6 theme reduced 1127:1133 arg1 levels 1135:1140 reduced levels 1127:1140 reduced levels of the COSMC mRNA and protein 1127:1170 Furthermore, TNF-α was shown to down-regulate the COSMC gene as evidenced by reduced levels of the COSMC mRNA and protein, as well as hypermethylation of the CpG islands of the COSMC gene promoter. 27542280 1 7 theme cancer 258:263 arg1 progression 265:275 cancer progression 258:275 cancer progression 258:275 Tn antigen (GalNAc-α-O-Ser/Thr), a mucin-type O-linked glycan, is a well-established cell surface marker for tumors and its elevated levels have been correlated with cancer progression and prognosis. 27542280 8 8 theme COSMC 1149:1153 arg1 mRNA 1155:1158 COSMC mRNA 1149:1158 COSMC mRNA 1149:1158 Furthermore, TNF-α was shown to down-regulate the COSMC gene as evidenced by reduced levels of the COSMC mRNA and protein, as well as hypermethylation of the CpG islands of the COSMC gene promoter. 27542280 4 9 theme current 463:469 arg1 studies 471:477 the current studies 459:477 the current studies 459:477 In the current studies, we have explored the possibility that cytokines may be one of the common regulatory molecules for elevated Tn levels in both cancer and inflammation. 27542280 7 10 theme purified 947:954 arg1 IL-6 997:1000 IL-6 997:1000 IL-6 997:1000 Indeed, purified inflammatory cytokines such as TNF-α and IL-6 up-regulated Tn levels in gingival fibroblasts. 27542280 7 10 theme purified 947:954 arg1 cytokines 969:977 purified inflammatory cytokines 947:977 purified inflammatory cytokines such as TNF-α and IL-6 947:1000 Indeed, purified inflammatory cytokines such as TNF-α and IL-6 up-regulated Tn levels in gingival fibroblasts. 27542280 7 10 theme purified 947:954 arg1 TNF-α 987:991 TNF-α 987:991 TNF-α 987:991 Indeed, purified inflammatory cytokines such as TNF-α and IL-6 up-regulated Tn levels in gingival fibroblasts. 27542280 4 11 theme molecules 564:572 arg1 molecules 564:572 the common regulatory molecules 542:572 the common regulatory molecules 542:572 In the current studies, we have explored the possibility that cytokines may be one of the common regulatory molecules for elevated Tn levels in both cancer and inflammation. 27542280 4 11 theme molecules 564:572 arg1 one 535:537 one 535:537 one 535:537 In the current studies, we have explored the possibility that cytokines may be one of the common regulatory molecules for elevated Tn levels in both cancer and inflammation. 27542280 5 12 theme HrasG12V-transformed-BEAS-2B 698:725 arg1 cells 727:731 HrasG12V-transformed-BEAS-2B cells 698:731 HrasG12V-transformed-BEAS-2B cells 698:731 We showed that the Tn level is elevated by the conditioned media of HrasG12V-transformed-BEAS-2B cells. 27542280 8 13 theme protein 1164:1170 arg1 levels 1135:1140 reduced levels 1127:1140 reduced levels of the COSMC mRNA and protein 1127:1170 Furthermore, TNF-α was shown to down-regulate the COSMC gene as evidenced by reduced levels of the COSMC mRNA and protein, as well as hypermethylation of the CpG islands of the COSMC gene promoter. 27542280 8 13 theme protein 1164:1170 arg1 hypermethylation 1184:1199 hypermethylation 1184:1199 hypermethylation of the CpG islands of the COSMC gene promoter 1184:1245 Furthermore, TNF-α was shown to down-regulate the COSMC gene as evidenced by reduced levels of the COSMC mRNA and protein, as well as hypermethylation of the CpG islands of the COSMC gene promoter. 27542280 6 14 theme LPS-stimulated 781:794 arg1 monocytes 796:804 LPS-stimulated monocytes 781:804 LPS-stimulated monocytes 781:804 Similarly, the conditioned media obtained from LPS-stimulated monocytes also elevated Tn levels in primary human gingival fibroblasts, suggesting the involvement of cytokines and/or other soluble factors. 27542280 8 15 theme COSMC 1227:1231 arg1 promoter 1238:1245 the COSMC gene promoter 1223:1245 the COSMC gene promoter 1223:1245 Furthermore, TNF-α was shown to down-regulate the COSMC gene as evidenced by reduced levels of the COSMC mRNA and protein, as well as hypermethylation of the CpG islands of the COSMC gene promoter. 27542280 1 16 theme well-established 160:175 arg1 marker 190:195 a well-established cell surface marker 158:195 a well-established cell surface marker for tumors 158:206 Tn antigen (GalNAc-α-O-Ser/Thr), a mucin-type O-linked glycan, is a well-established cell surface marker for tumors and its elevated levels have been correlated with cancer progression and prognosis. 27542280 1 16 theme well-established 160:175 arg1 antigen 95:101 Tn antigen 92:101 Tn antigen (GalNAc-α-O-Ser/Thr) 92:122 Tn antigen (GalNAc-α-O-Ser/Thr), a mucin-type O-linked glycan, is a well-established cell surface marker for tumors and its elevated levels have been correlated with cancer progression and prognosis. 27542280 5 17 theme cells 727:731 arg1 media 689:693 the conditioned media 673:693 the conditioned media of HrasG12V-transformed-BEAS-2B cells 673:731 We showed that the Tn level is elevated by the conditioned media of HrasG12V-transformed-BEAS-2B cells. 27542280 9 18 dep suggest 1344:1350 arg1 regulated 1414:1422 regulated 1414:1422 suggest elevated Tn levels in cancer and inflammation may be commonly regulated by the cytokine-Cosmc signaling axis 1344:1459 Since Cosmc, a chaperone for T-synthase, is known to negatively regulate Tn levels, our results suggest elevated Tn levels in cancer and inflammation may be commonly regulated by the cytokine-Cosmc signaling axis. 27542280 6 19 theme human 841:845 arg1 fibroblasts 856:866 primary human gingival fibroblasts 833:866 primary human gingival fibroblasts 833:866 Similarly, the conditioned media obtained from LPS-stimulated monocytes also elevated Tn levels in primary human gingival fibroblasts, suggesting the involvement of cytokines and/or other soluble factors. 27542280 1 20 theme Tn 92:93 arg1 marker 190:195 a well-established cell surface marker 158:195 a well-established cell surface marker for tumors 158:206 Tn antigen (GalNAc-α-O-Ser/Thr), a mucin-type O-linked glycan, is a well-established cell surface marker for tumors and its elevated levels have been correlated with cancer progression and prognosis. 27542280 1 20 theme Tn 92:93 arg1 GalNAc-α-O-Ser/Thr 104:121 GalNAc-α-O-Ser/Thr 104:121 GalNAc-α-O-Ser/Thr 104:121 Tn antigen (GalNAc-α-O-Ser/Thr), a mucin-type O-linked glycan, is a well-established cell surface marker for tumors and its elevated levels have been correlated with cancer progression and prognosis. 27542280 1 20 theme Tn 92:93 arg1 glycan 147:152 a mucin-type O-linked glycan 125:152 a mucin-type O-linked glycan 125:152 Tn antigen (GalNAc-α-O-Ser/Thr), a mucin-type O-linked glycan, is a well-established cell surface marker for tumors and its elevated levels have been correlated with cancer progression and prognosis. 27542280 1 20 theme Tn 92:93 arg1 antigen 95:101 Tn antigen 92:101 Tn antigen (GalNAc-α-O-Ser/Thr) 92:122 Tn antigen (GalNAc-α-O-Ser/Thr), a mucin-type O-linked glycan, is a well-established cell surface marker for tumors and its elevated levels have been correlated with cancer progression and prognosis. 27542280 1 21 theme cell 177:180 arg1 marker 190:195 a well-established cell surface marker 158:195 a well-established cell surface marker for tumors 158:206 Tn antigen (GalNAc-α-O-Ser/Thr), a mucin-type O-linked glycan, is a well-established cell surface marker for tumors and its elevated levels have been correlated with cancer progression and prognosis. 27542280 1 21 theme cell 177:180 arg1 antigen 95:101 Tn antigen 92:101 Tn antigen (GalNAc-α-O-Ser/Thr) 92:122 Tn antigen (GalNAc-α-O-Ser/Thr), a mucin-type O-linked glycan, is a well-established cell surface marker for tumors and its elevated levels have been correlated with cancer progression and prognosis. 27542280 0 22 theme cytokine-cosmc 4:17 arg1 axis 29:32 The cytokine-cosmc signaling axis 0:32 The cytokine-cosmc signaling axis 0:32 The cytokine-cosmc signaling axis upregulates the tumor-associated carbohydrate antigen Tn. 27542280 3 23 from mechanism 383:391 arg1 inflammation 431:442 inflammation 431:442 inflammation 431:442 However, the molecular mechanism for its elevated levels in cancer and inflammation is unclear. 27542280 3 23 from mechanism 383:391 arg1 cancer 420:425 cancer 420:425 cancer 420:425 However, the molecular mechanism for its elevated levels in cancer and inflammation is unclear. 27542280 5 24 theme Tn 649:650 arg1 level 652:656 the Tn level 645:656 the Tn level 645:656 We showed that the Tn level is elevated by the conditioned media of HrasG12V-transformed-BEAS-2B cells. 27542280 1 25 theme surface 182:188 arg1 marker 190:195 a well-established cell surface marker 158:195 a well-established cell surface marker for tumors 158:206 Tn antigen (GalNAc-α-O-Ser/Thr), a mucin-type O-linked glycan, is a well-established cell surface marker for tumors and its elevated levels have been correlated with cancer progression and prognosis. 27542280 1 25 theme surface 182:188 arg1 antigen 95:101 Tn antigen 92:101 Tn antigen (GalNAc-α-O-Ser/Thr) 92:122 Tn antigen (GalNAc-α-O-Ser/Thr), a mucin-type O-linked glycan, is a well-established cell surface marker for tumors and its elevated levels have been correlated with cancer progression and prognosis. 27542280 9 26 from levels 1364:1369 arg1 inflammation 1385:1396 inflammation 1385:1396 inflammation 1385:1396 Since Cosmc, a chaperone for T-synthase, is known to negatively regulate Tn levels, our results suggest elevated Tn levels in cancer and inflammation may be commonly regulated by the cytokine-Cosmc signaling axis. 27542280 9 26 from levels 1364:1369 arg1 cancer 1374:1379 cancer 1374:1379 cancer 1374:1379 Since Cosmc, a chaperone for T-synthase, is known to negatively regulate Tn levels, our results suggest elevated Tn levels in cancer and inflammation may be commonly regulated by the cytokine-Cosmc signaling axis. 27542280 6 27 theme conditioned 749:759 arg1 media 761:765 the conditioned media 745:765 the conditioned media obtained from LPS-stimulated monocytes 745:804 Similarly, the conditioned media obtained from LPS-stimulated monocytes also elevated Tn levels in primary human gingival fibroblasts, suggesting the involvement of cytokines and/or other soluble factors. 27542280 8 28 theme promoter 1238:1245 arg1 islands 1212:1218 the CpG islands 1204:1218 the CpG islands of the COSMC gene promoter 1204:1245 Furthermore, TNF-α was shown to down-regulate the COSMC gene as evidenced by reduced levels of the COSMC mRNA and protein, as well as hypermethylation of the CpG islands of the COSMC gene promoter. 27542280 0 29 theme signaling 19:27 arg1 axis 29:32 The cytokine-cosmc signaling axis 0:32 The cytokine-cosmc signaling axis 0:32 The cytokine-cosmc signaling axis upregulates the tumor-associated carbohydrate antigen Tn. 27542280 7 30 theme inflammatory 956:967 arg1 IL-6 997:1000 IL-6 997:1000 IL-6 997:1000 Indeed, purified inflammatory cytokines such as TNF-α and IL-6 up-regulated Tn levels in gingival fibroblasts. 27542280 7 30 theme inflammatory 956:967 arg1 cytokines 969:977 purified inflammatory cytokines 947:977 purified inflammatory cytokines such as TNF-α and IL-6 947:1000 Indeed, purified inflammatory cytokines such as TNF-α and IL-6 up-regulated Tn levels in gingival fibroblasts. 27542280 7 30 theme inflammatory 956:967 arg1 TNF-α 987:991 TNF-α 987:991 TNF-α 987:991 Indeed, purified inflammatory cytokines such as TNF-α and IL-6 up-regulated Tn levels in gingival fibroblasts. 27542280 8 31 theme gene 1233:1236 arg1 promoter 1238:1245 the COSMC gene promoter 1223:1245 the COSMC gene promoter 1223:1245 Furthermore, TNF-α was shown to down-regulate the COSMC gene as evidenced by reduced levels of the COSMC mRNA and protein, as well as hypermethylation of the CpG islands of the COSMC gene promoter. 27542280 3 32 theme elevated 401:408 arg1 levels 410:415 its elevated levels 397:415 its elevated levels 397:415 However, the molecular mechanism for its elevated levels in cancer and inflammation is unclear. 27542280 8 33 theme COSMC 1100:1104 arg1 gene 1106:1109 the COSMC gene 1096:1109 the COSMC gene 1096:1109 Furthermore, TNF-α was shown to down-regulate the COSMC gene as evidenced by reduced levels of the COSMC mRNA and protein, as well as hypermethylation of the CpG islands of the COSMC gene promoter. 27542280 8 34 theme islands 1212:1218 arg1 levels 1135:1140 reduced levels 1127:1140 reduced levels of the COSMC mRNA and protein 1127:1170 Furthermore, TNF-α was shown to down-regulate the COSMC gene as evidenced by reduced levels of the COSMC mRNA and protein, as well as hypermethylation of the CpG islands of the COSMC gene promoter. 27542280 8 34 theme islands 1212:1218 arg1 hypermethylation 1184:1199 hypermethylation 1184:1199 hypermethylation of the CpG islands of the COSMC gene promoter 1184:1245 Furthermore, TNF-α was shown to down-regulate the COSMC gene as evidenced by reduced levels of the COSMC mRNA and protein, as well as hypermethylation of the CpG islands of the COSMC gene promoter. 27542280 9 35 theme Tn 1321:1322 arg1 levels 1324:1329 Tn levels 1321:1329 Tn levels 1321:1329 Since Cosmc, a chaperone for T-synthase, is known to negatively regulate Tn levels, our results suggest elevated Tn levels in cancer and inflammation may be commonly regulated by the cytokine-Cosmc signaling axis. 27542280 5 36 theme conditioned 677:687 arg1 media 689:693 the conditioned media 673:693 the conditioned media of HrasG12V-transformed-BEAS-2B cells 673:731 We showed that the Tn level is elevated by the conditioned media of HrasG12V-transformed-BEAS-2B cells. 27542280 6 37 theme gingival 847:854 arg1 fibroblasts 856:866 primary human gingival fibroblasts 833:866 primary human gingival fibroblasts 833:866 Similarly, the conditioned media obtained from LPS-stimulated monocytes also elevated Tn levels in primary human gingival fibroblasts, suggesting the involvement of cytokines and/or other soluble factors. 27542280 9 38 theme cytokine-Cosmc 1431:1444 arg1 axis 1456:1459 the cytokine-Cosmc signaling axis 1427:1459 the cytokine-Cosmc signaling axis 1427:1459 Since Cosmc, a chaperone for T-synthase, is known to negatively regulate Tn levels, our results suggest elevated Tn levels in cancer and inflammation may be commonly regulated by the cytokine-Cosmc signaling axis. 27542280 0 39 theme carbohydrate 67:78 arg1 Tn 88:89 the tumor-associated carbohydrate antigen Tn 46:89 the tumor-associated carbohydrate antigen Tn 46:89 The cytokine-cosmc signaling axis upregulates the tumor-associated carbohydrate antigen Tn. 27542280 4 40 from levels 590:595 arg1 inflammation 616:627 inflammation 616:627 inflammation 616:627 In the current studies, we have explored the possibility that cytokines may be one of the common regulatory molecules for elevated Tn levels in both cancer and inflammation. 27542280 4 40 from levels 590:595 arg1 cancer 605:610 cancer 605:610 cancer 605:610 In the current studies, we have explored the possibility that cytokines may be one of the common regulatory molecules for elevated Tn levels in both cancer and inflammation. 27542280 9 41 theme signaling 1446:1454 arg1 axis 1456:1459 the cytokine-Cosmc signaling axis 1427:1459 the cytokine-Cosmc signaling axis 1427:1459 Since Cosmc, a chaperone for T-synthase, is known to negatively regulate Tn levels, our results suggest elevated Tn levels in cancer and inflammation may be commonly regulated by the cytokine-Cosmc signaling axis. 27542280 0 42 theme tumor-associated 50:65 arg1 Tn 88:89 the tumor-associated carbohydrate antigen Tn 46:89 the tumor-associated carbohydrate antigen Tn 46:89 The cytokine-cosmc signaling axis upregulates the tumor-associated carbohydrate antigen Tn. 27542280 1 43 link O-linked 138:145 arg1 antigen 95:101 Tn antigen 92:101 Tn antigen (GalNAc-α-O-Ser/Thr) 92:122 Tn antigen (GalNAc-α-O-Ser/Thr), a mucin-type O-linked glycan, is a well-established cell surface marker for tumors and its elevated levels have been correlated with cancer progression and prognosis. 27542280 1 43 link O-linked 138:145 arg1 glycan 147:152 a mucin-type O-linked glycan 125:152 a mucin-type O-linked glycan 125:152 Tn antigen (GalNAc-α-O-Ser/Thr), a mucin-type O-linked glycan, is a well-established cell surface marker for tumors and its elevated levels have been correlated with cancer progression and prognosis. 27542280 6 44 theme primary 833:839 arg1 fibroblasts 856:866 primary human gingival fibroblasts 833:866 primary human gingival fibroblasts 833:866 Similarly, the conditioned media obtained from LPS-stimulated monocytes also elevated Tn levels in primary human gingival fibroblasts, suggesting the involvement of cytokines and/or other soluble factors. 27542280 6 45 theme factors 930:936 arg1 involvement 884:894 the involvement 880:894 the involvement of cytokines and/or other soluble factors 880:936 Similarly, the conditioned media obtained from LPS-stimulated monocytes also elevated Tn levels in primary human gingival fibroblasts, suggesting the involvement of cytokines and/or other soluble factors. 27542280 7 46 theme gingival 1028:1035 arg1 fibroblasts 1037:1047 gingival fibroblasts 1028:1047 gingival fibroblasts 1028:1047 Indeed, purified inflammatory cytokines such as TNF-α and IL-6 up-regulated Tn levels in gingival fibroblasts. 27542280 7 47 theme Tn 1015:1016 arg1 levels 1018:1023 Tn levels 1015:1023 Tn levels 1015:1023 Indeed, purified inflammatory cytokines such as TNF-α and IL-6 up-regulated Tn levels in gingival fibroblasts. 27542280 1 48 theme mucin-type 127:136 arg1 antigen 95:101 Tn antigen 92:101 Tn antigen (GalNAc-α-O-Ser/Thr) 92:122 Tn antigen (GalNAc-α-O-Ser/Thr), a mucin-type O-linked glycan, is a well-established cell surface marker for tumors and its elevated levels have been correlated with cancer progression and prognosis. 27542280 1 48 theme mucin-type 127:136 arg1 glycan 147:152 a mucin-type O-linked glycan 125:152 a mucin-type O-linked glycan 125:152 Tn antigen (GalNAc-α-O-Ser/Thr), a mucin-type O-linked glycan, is a well-established cell surface marker for tumors and its elevated levels have been correlated with cancer progression and prognosis. 27542280 4 49 theme Tn 587:588 arg1 levels 590:595 elevated Tn levels 578:595 elevated Tn levels in both cancer and inflammation 578:627 In the current studies, we have explored the possibility that cytokines may be one of the common regulatory molecules for elevated Tn levels in both cancer and inflammation. 27542280 1 50 theme O-linked 138:145 arg1 antigen 95:101 Tn antigen 92:101 Tn antigen (GalNAc-α-O-Ser/Thr) 92:122 Tn antigen (GalNAc-α-O-Ser/Thr), a mucin-type O-linked glycan, is a well-established cell surface marker for tumors and its elevated levels have been correlated with cancer progression and prognosis. 27542280 1 50 theme O-linked 138:145 arg1 glycan 147:152 a mucin-type O-linked glycan 125:152 a mucin-type O-linked glycan 125:152 Tn antigen (GalNAc-α-O-Ser/Thr), a mucin-type O-linked glycan, is a well-established cell surface marker for tumors and its elevated levels have been correlated with cancer progression and prognosis. 27542280 8 51 theme CpG 1208:1210 arg1 islands 1212:1218 the CpG islands 1204:1218 the CpG islands of the COSMC gene promoter 1204:1245 Furthermore, TNF-α was shown to down-regulate the COSMC gene as evidenced by reduced levels of the COSMC mRNA and protein, as well as hypermethylation of the CpG islands of the COSMC gene promoter. 27542280 4 52 theme elevated 578:585 arg1 levels 590:595 elevated Tn levels 578:595 elevated Tn levels in both cancer and inflammation 578:627 In the current studies, we have explored the possibility that cytokines may be one of the common regulatory molecules for elevated Tn levels in both cancer and inflammation. 27542280 6 53 theme Tn 820:821 arg1 levels 823:828 Tn levels 820:828 Tn levels 820:828 Similarly, the conditioned media obtained from LPS-stimulated monocytes also elevated Tn levels in primary human gingival fibroblasts, suggesting the involvement of cytokines and/or other soluble factors. 27542280 3 54 theme molecular 373:381 arg1 unclear 447:453 unclear 447:453 unclear 447:453 However, the molecular mechanism for its elevated levels in cancer and inflammation is unclear. 27542280 3 54 theme molecular 373:381 arg1 mechanism 383:391 the molecular mechanism 369:391 the molecular mechanism for its elevated levels in cancer and inflammation 369:442 However, the molecular mechanism for its elevated levels in cancer and inflammation is unclear. 27542280 9 55 theme elevated 1352:1359 arg1 levels 1364:1369 elevated Tn levels 1352:1369 elevated Tn levels in cancer and inflammation 1352:1396 Since Cosmc, a chaperone for T-synthase, is known to negatively regulate Tn levels, our results suggest elevated Tn levels in cancer and inflammation may be commonly regulated by the cytokine-Cosmc signaling axis. 27542280 0 56 theme antigen 80:86 arg1 Tn 88:89 the tumor-associated carbohydrate antigen Tn 46:89 the tumor-associated carbohydrate antigen Tn 46:89 The cytokine-cosmc signaling axis upregulates the tumor-associated carbohydrate antigen Tn. 27542280 6 57 theme soluble 922:928 arg1 factors 930:936 other soluble factors 916:936 other soluble factors 916:936 Similarly, the conditioned media obtained from LPS-stimulated monocytes also elevated Tn levels in primary human gingival fibroblasts, suggesting the involvement of cytokines and/or other soluble factors. 27542280 1 58 theme elevated 216:223 arg1 levels 225:230 its elevated levels 212:230 its elevated levels 212:230 Tn antigen (GalNAc-α-O-Ser/Thr), a mucin-type O-linked glycan, is a well-established cell surface marker for tumors and its elevated levels have been correlated with cancer progression and prognosis. 27542280 9 59 theme Tn 1361:1362 arg1 levels 1364:1369 elevated Tn levels 1352:1369 elevated Tn levels in cancer and inflammation 1352:1396 Since Cosmc, a chaperone for T-synthase, is known to negatively regulate Tn levels, our results suggest elevated Tn levels in cancer and inflammation may be commonly regulated by the cytokine-Cosmc signaling axis. 27340695 4 0 theme de 793:794 arg1 procedures 810:819 de novo assembly procedures 793:819 de novo assembly procedures 793:819 Here, we determined the complete 206-kb genome of EEHV4(Baylor) directly from trunk wash DNA by next-generation sequencing and de novo assembly procedures. 27340695 3 1 theme second 616:621 arg1 branch 629:634 a hugely diverged second major branch 598:634 a hugely diverged second major branch with GC-rich characteristics 598:663 However, less than 6 kb of DNA sequence each from EEHV3, EEHV4, and EEHV7 showed them to be a hugely diverged second major branch with GC-rich characteristics. 27340695 3 2 with branch 629:634 arg1 characteristics 649:663 GC-rich characteristics 641:663 GC-rich characteristics 641:663 However, less than 6 kb of DNA sequence each from EEHV3, EEHV4, and EEHV7 showed them to be a hugely diverged second major branch with GC-rich characteristics. 27340695 12 3 theme disease 2546:2552 arg1 episode 2554:2560 an acute hemorrhagic disease episode 2525:2560 an acute hemorrhagic disease episode 2525:2560 Here, we have determined the complete genomic DNA sequence of a strain of EEHV4 obtained from a trunk wash sample collected from a surviving Asian elephant calf undergoing asymptomatic shedding during convalescence after an acute hemorrhagic disease episode. 27340695 4 4 theme assembly 801:808 arg1 procedures 810:819 de novo assembly procedures 793:819 de novo assembly procedures 793:819 Here, we determined the complete 206-kb genome of EEHV4(Baylor) directly from trunk wash DNA by next-generation sequencing and de novo assembly procedures. 27340695 6 5 theme unusual 1070:1076 arg1 distribution 1078:1089 an unusual distribution 1067:1089 an unusual distribution of tracts of 5 to 11 successive A or T nucleotides in intergenic domains between the mostly much higher GC content protein coding regions 1067:1227 The genome also contains an unusual distribution of tracts of 5 to 11 successive A or T nucleotides in intergenic domains between the mostly much higher GC content protein coding regions. 27340695 9 6 theme EEHV4A 1713:1718 arg1 subtypes 1731:1738 distinct EEHV4A and EEHV4B subtypes 1704:1738 distinct EEHV4A and EEHV4B subtypes 1704:1738 Finally, 30 kb from a second strain proved to include three small chimeric domains, indicating the existence of distinct EEHV4A and EEHV4B subtypes. 27340695 8 7 theme acetylglucosamine 1482:1498 arg1 vOGT 1513:1516 vOGT 1513:1516 vOGT 1513:1516 There are also two novel captured cellular genes, including a C-type lectin (vECTL) and an O-linked acetylglucosamine transferase (vOGT), as well as an unusually large and complex Ori-Lyt dyad symmetry domain. 27340695 8 7 theme acetylglucosamine 1482:1498 arg1 transferase 1500:1510 an O-linked acetylglucosamine transferase 1470:1510 an O-linked acetylglucosamine transferase (vOGT) 1470:1517 There are also two novel captured cellular genes, including a C-type lectin (vECTL) and an O-linked acetylglucosamine transferase (vOGT), as well as an unusually large and complex Ori-Lyt dyad symmetry domain. 27340695 14 8 theme AT-rich 2748:2754 arg1 genomes 2763:2769 AT-rich branch genomes 2748:2769 AT-rich branch genomes 2748:2769 Several distinctive features of EEHV4 compared to AT-rich branch genomes are described. 27340695 7 9 theme coding 1336:1341 arg1 regions 1343:1349 the coding regions 1332:1349 the coding regions for many but not all proteins 1332:1379 Furthermore, an extremely high GC-rich bias in the third wobble position of codons clearly delineates the coding regions for many but not all proteins. 27340695 7 10 theme wobble 1287:1292 arg1 position 1294:1301 the third wobble position 1277:1301 the third wobble position of codons 1277:1311 Furthermore, an extremely high GC-rich bias in the third wobble position of codons clearly delineates the coding regions for many but not all proteins. 27340695 9 11 theme EEHV4B 1724:1729 arg1 subtypes 1731:1738 distinct EEHV4A and EEHV4B subtypes 1704:1738 distinct EEHV4A and EEHV4B subtypes 1704:1738 Finally, 30 kb from a second strain proved to include three small chimeric domains, indicating the existence of distinct EEHV4A and EEHV4B subtypes. 27340695 10 12 from species 1761:1767 arg1 lineages 1807:1814 three different lineages 1791:1814 three different lineages of the Proboscivirus genus (EEHV1/6, EEHV2/5, and EEHV3/4/7) 1791:1875 IMPORTANCE Multiple species of herpesviruses from three different lineages of the Proboscivirus genus (EEHV1/6, EEHV2/5, and EEHV3/4/7) infect both Asian and African elephants, but lethal hemorrhagic disease is largely confined to Asian elephant calves and is predominantly associated with EEHV1. 27340695 3 13 theme GC-rich 641:647 arg1 characteristics 649:663 GC-rich characteristics 641:663 GC-rich characteristics 641:663 However, less than 6 kb of DNA sequence each from EEHV3, EEHV4, and EEHV7 showed them to be a hugely diverged second major branch with GC-rich characteristics. 27340695 6 14 theme T 1128:1128 arg1 nucleotides 1130:1140 5 to 11 successive A or T nucleotides 1104:1140 5 to 11 successive A or T nucleotides 1104:1140 The genome also contains an unusual distribution of tracts of 5 to 11 successive A or T nucleotides in intergenic domains between the mostly much higher GC content protein coding regions. 27340695 9 15 from strain 1621:1626 arg1 kb 1604:1605 30 kb 1601:1605 30 kb from a second strain 1601:1626 Finally, 30 kb from a second strain proved to include three small chimeric domains, indicating the existence of distinct EEHV4A and EEHV4B subtypes. 27340695 12 16 theme acute 2528:2532 arg1 episode 2554:2560 an acute hemorrhagic disease episode 2525:2560 an acute hemorrhagic disease episode 2525:2560 Here, we have determined the complete genomic DNA sequence of a strain of EEHV4 obtained from a trunk wash sample collected from a surviving Asian elephant calf undergoing asymptomatic shedding during convalescence after an acute hemorrhagic disease episode. 27340695 10 17 theme different 1797:1805 arg1 lineages 1807:1814 three different lineages 1791:1814 three different lineages of the Proboscivirus genus (EEHV1/6, EEHV2/5, and EEHV3/4/7) 1791:1875 IMPORTANCE Multiple species of herpesviruses from three different lineages of the Proboscivirus genus (EEHV1/6, EEHV2/5, and EEHV3/4/7) infect both Asian and African elephants, but lethal hemorrhagic disease is largely confined to Asian elephant calves and is predominantly associated with EEHV1. 27340695 6 18 theme A 1123:1123 arg1 nucleotides 1130:1140 5 to 11 successive A or T nucleotides 1104:1140 5 to 11 successive A or T nucleotides 1104:1140 The genome also contains an unusual distribution of tracts of 5 to 11 successive A or T nucleotides in intergenic domains between the mostly much higher GC content protein coding regions. 27340695 3 19 theme DNA 533:535 arg1 sequence 537:544 DNA sequence 533:544 DNA sequence each from EEHV3, EEHV4, and EEHV7 533:578 However, less than 6 kb of DNA sequence each from EEHV3, EEHV4, and EEHV7 showed them to be a hugely diverged second major branch with GC-rich characteristics. 27340695 8 20 theme Ori-Lyt 1562:1568 arg1 domain 1584:1589 an unusually large and complex Ori-Lyt dyad symmetry domain 1531:1589 an unusually large and complex Ori-Lyt dyad symmetry domain 1531:1589 There are also two novel captured cellular genes, including a C-type lectin (vECTL) and an O-linked acetylglucosamine transferase (vOGT), as well as an unusually large and complex Ori-Lyt dyad symmetry domain. 27340695 1 21 theme endotheliotropic 177:192 arg1 EEHVs 209:213 EEHVs 209:213 EEHVs 209:213 A novel group of mammalian DNA viruses called elephant endotheliotropic herpesviruses (EEHVs) belonging to the Proboscivirus genus has been associated with nearly 100 cases of highly lethal acute hemorrhagic disease in young Asian elephants worldwide. 27340695 1 21 theme endotheliotropic 177:192 arg1 herpesviruses 194:206 elephant endotheliotropic herpesviruses 168:206 elephant endotheliotropic herpesviruses (EEHVs) belonging to the Proboscivirus genus 168:251 A novel group of mammalian DNA viruses called elephant endotheliotropic herpesviruses (EEHVs) belonging to the Proboscivirus genus has been associated with nearly 100 cases of highly lethal acute hemorrhagic disease in young Asian elephants worldwide. 27340695 12 22 theme asymptomatic 2476:2487 arg1 shedding 2489:2496 asymptomatic shedding 2476:2496 asymptomatic shedding 2476:2496 Here, we have determined the complete genomic DNA sequence of a strain of EEHV4 obtained from a trunk wash sample collected from a surviving Asian elephant calf undergoing asymptomatic shedding during convalescence after an acute hemorrhagic disease episode. 27340695 0 23 theme Proboscivirus 107:119 arg1 Sequence 16:23 Complete Genome Sequence 0:23 Complete Genome Sequence of Elephant Endotheliotropic Herpesvirus 4 0:66 Complete Genome Sequence of Elephant Endotheliotropic Herpesvirus 4, the First Example of a GC-Rich Branch Proboscivirus. 27340695 0 23 theme Proboscivirus 107:119 arg1 Example 79:85 the First Example 69:85 the First Example of a GC-Rich Branch Proboscivirus 69:119 Complete Genome Sequence of Elephant Endotheliotropic Herpesvirus 4, the First Example of a GC-Rich Branch Proboscivirus. 27340695 8 24 theme symmetry 1575:1582 arg1 domain 1584:1589 an unusually large and complex Ori-Lyt dyad symmetry domain 1531:1589 an unusually large and complex Ori-Lyt dyad symmetry domain 1531:1589 There are also two novel captured cellular genes, including a C-type lectin (vECTL) and an O-linked acetylglucosamine transferase (vOGT), as well as an unusually large and complex Ori-Lyt dyad symmetry domain. 27340695 6 25 dep content 1198:1204 arg1 regions 1221:1227 protein coding regions 1206:1227 the mostly much higher GC content protein coding regions 1172:1227 The genome also contains an unusual distribution of tracts of 5 to 11 successive A or T nucleotides in intergenic domains between the mostly much higher GC content protein coding regions. 27340695 10 26 theme African 1899:1905 arg1 elephants 1907:1915 both Asian and African elephants 1884:1915 both Asian and African elephants 1884:1915 IMPORTANCE Multiple species of herpesviruses from three different lineages of the Proboscivirus genus (EEHV1/6, EEHV2/5, and EEHV3/4/7) infect both Asian and African elephants, but lethal hemorrhagic disease is largely confined to Asian elephant calves and is predominantly associated with EEHV1. 27340695 6 27 theme successive 1112:1121 arg1 nucleotides 1130:1140 5 to 11 successive A or T nucleotides 1104:1140 5 to 11 successive A or T nucleotides 1104:1140 The genome also contains an unusual distribution of tracts of 5 to 11 successive A or T nucleotides in intergenic domains between the mostly much higher GC content protein coding regions. 27340695 10 28 theme Proboscivirus 1823:1835 arg1 genus 1837:1841 the Proboscivirus genus 1819:1841 the Proboscivirus genus (EEHV1/6, EEHV2/5, and EEHV3/4/7) 1819:1875 IMPORTANCE Multiple species of herpesviruses from three different lineages of the Proboscivirus genus (EEHV1/6, EEHV2/5, and EEHV3/4/7) infect both Asian and African elephants, but lethal hemorrhagic disease is largely confined to Asian elephant calves and is predominantly associated with EEHV1. 27340695 6 29 theme GC 1195:1196 arg1 content 1198:1204 the mostly much higher GC content protein coding regions 1172:1227 the mostly much higher GC content protein coding regions 1172:1227 The genome also contains an unusual distribution of tracts of 5 to 11 successive A or T nucleotides in intergenic domains between the mostly much higher GC content protein coding regions. 27340695 5 30 theme paralogous 973:982 arg1 genes 1004:1008 26 paralogous 7xTM and vGPCR-like genes 970:1008 26 paralogous 7xTM and vGPCR-like genes 970:1008 Among a total of 119 genes with an overall colinear organization similar to those of the AT-rich EEHVs, major features of EEHV4 include a family of 26 paralogous 7xTM and vGPCR-like genes plus 25 novel or missing genes. 27340695 13 31 theme Proboscivirus 2639:2651 arg1 species 2653:2659 the three known GC-rich branch Proboscivirus species 2608:2659 the three known GC-rich branch Proboscivirus species 2608:2659 This represents the first example from among the three known GC-rich branch Proboscivirus species to be assembled and fully annotated. 27340695 12 32 theme Asian 2445:2449 arg1 elephant 2451:2458 a surviving Asian elephant 2433:2458 a surviving Asian elephant calf undergoing asymptomatic shedding during convalescence 2433:2517 Here, we have determined the complete genomic DNA sequence of a strain of EEHV4 obtained from a trunk wash sample collected from a surviving Asian elephant calf undergoing asymptomatic shedding during convalescence after an acute hemorrhagic disease episode. 27340695 5 33 theme EEHV4 944:948 arg1 features 932:939 major features 926:939 major features of EEHV4 926:948 Among a total of 119 genes with an overall colinear organization similar to those of the AT-rich EEHVs, major features of EEHV4 include a family of 26 paralogous 7xTM and vGPCR-like genes plus 25 novel or missing genes. 27340695 10 34 dep genus 1837:1841 arg1 EEHV1/6 1844:1850 EEHV1/6 1844:1850 EEHV1/6 1844:1850 IMPORTANCE Multiple species of herpesviruses from three different lineages of the Proboscivirus genus (EEHV1/6, EEHV2/5, and EEHV3/4/7) infect both Asian and African elephants, but lethal hemorrhagic disease is largely confined to Asian elephant calves and is predominantly associated with EEHV1. 27340695 10 34 dep genus 1837:1841 arg1 EEHV2/5 1853:1859 EEHV2/5 1853:1859 EEHV2/5 1853:1859 IMPORTANCE Multiple species of herpesviruses from three different lineages of the Proboscivirus genus (EEHV1/6, EEHV2/5, and EEHV3/4/7) infect both Asian and African elephants, but lethal hemorrhagic disease is largely confined to Asian elephant calves and is predominantly associated with EEHV1. 27340695 10 34 dep genus 1837:1841 arg1 EEHV3/4/7 1866:1874 EEHV3/4/7 1866:1874 EEHV3/4/7 1866:1874 IMPORTANCE Multiple species of herpesviruses from three different lineages of the Proboscivirus genus (EEHV1/6, EEHV2/5, and EEHV3/4/7) infect both Asian and African elephants, but lethal hemorrhagic disease is largely confined to Asian elephant calves and is predominantly associated with EEHV1. 27340695 14 35 theme branch 2756:2761 arg1 genomes 2763:2769 AT-rich branch genomes 2748:2769 AT-rich branch genomes 2748:2769 Several distinctive features of EEHV4 compared to AT-rich branch genomes are described. 27340695 7 36 from bias 1269:1272 arg1 position 1294:1301 the third wobble position 1277:1301 the third wobble position of codons 1277:1311 Furthermore, an extremely high GC-rich bias in the third wobble position of codons clearly delineates the coding regions for many but not all proteins. 27340695 10 37 theme hemorrhagic 1929:1939 arg1 disease 1941:1947 lethal hemorrhagic disease 1922:1947 lethal hemorrhagic disease 1922:1947 IMPORTANCE Multiple species of herpesviruses from three different lineages of the Proboscivirus genus (EEHV1/6, EEHV2/5, and EEHV3/4/7) infect both Asian and African elephants, but lethal hemorrhagic disease is largely confined to Asian elephant calves and is predominantly associated with EEHV1. 27340695 10 38 theme Asian 1972:1976 arg1 calves 1987:1992 Asian elephant calves 1972:1992 Asian elephant calves 1972:1992 IMPORTANCE Multiple species of herpesviruses from three different lineages of the Proboscivirus genus (EEHV1/6, EEHV2/5, and EEHV3/4/7) infect both Asian and African elephants, but lethal hemorrhagic disease is largely confined to Asian elephant calves and is predominantly associated with EEHV1. 27340695 3 39 from kb 527:528 arg1 EEHV4 563:567 EEHV4 563:567 EEHV4 563:567 However, less than 6 kb of DNA sequence each from EEHV3, EEHV4, and EEHV7 showed them to be a hugely diverged second major branch with GC-rich characteristics. 27340695 3 39 from kb 527:528 arg1 EEHV7 574:578 EEHV7 574:578 EEHV7 574:578 However, less than 6 kb of DNA sequence each from EEHV3, EEHV4, and EEHV7 showed them to be a hugely diverged second major branch with GC-rich characteristics. 27340695 3 39 from kb 527:528 arg1 EEHV3 556:560 EEHV3 556:560 EEHV3 556:560 However, less than 6 kb of DNA sequence each from EEHV3, EEHV4, and EEHV7 showed them to be a hugely diverged second major branch with GC-rich characteristics. 27340695 5 40 theme genes 843:847 arg1 total 830:834 a total 828:834 a total of 119 genes with an overall colinear organization similar to those of the AT-rich EEHVs 828:923 Among a total of 119 genes with an overall colinear organization similar to those of the AT-rich EEHVs, major features of EEHV4 include a family of 26 paralogous 7xTM and vGPCR-like genes plus 25 novel or missing genes. 27340695 11 41 theme Milder 2038:2043 arg1 disease 2045:2051 Milder disease 2038:2051 Milder disease caused by EEHV5 or EEHV4 2038:2076 Milder disease caused by EEHV5 or EEHV4 is being increasingly recognized as well, but little is known about the latter, which is estimated to have diverged at least 35 million years ago from the others within a distinctive GC-rich branch of the Proboscivirus genus. 27340695 11 41 theme Milder 2038:2043 arg1 well 2114:2117 well 2114:2117 well 2114:2117 Milder disease caused by EEHV5 or EEHV4 is being increasingly recognized as well, but little is known about the latter, which is estimated to have diverged at least 35 million years ago from the others within a distinctive GC-rich branch of the Proboscivirus genus. 27340695 1 42 theme hemorrhagic 318:328 arg1 disease 330:336 highly lethal acute hemorrhagic disease 298:336 highly lethal acute hemorrhagic disease in young Asian elephants worldwide 298:371 A novel group of mammalian DNA viruses called elephant endotheliotropic herpesviruses (EEHVs) belonging to the Proboscivirus genus has been associated with nearly 100 cases of highly lethal acute hemorrhagic disease in young Asian elephants worldwide. 27340695 13 43 theme GC-rich 2624:2630 arg1 species 2653:2659 the three known GC-rich branch Proboscivirus species 2608:2659 the three known GC-rich branch Proboscivirus species 2608:2659 This represents the first example from among the three known GC-rich branch Proboscivirus species to be assembled and fully annotated. 27340695 12 44 theme trunk 2400:2404 arg1 sample 2411:2416 a trunk wash sample 2398:2416 a trunk wash sample collected from a surviving Asian elephant calf undergoing asymptomatic shedding during convalescence after an acute hemorrhagic disease episode 2398:2560 Here, we have determined the complete genomic DNA sequence of a strain of EEHV4 obtained from a trunk wash sample collected from a surviving Asian elephant calf undergoing asymptomatic shedding during convalescence after an acute hemorrhagic disease episode. 27340695 6 45 from distribution 1078:1089 arg1 domains 1156:1162 intergenic domains 1145:1162 intergenic domains between the mostly much higher GC content protein coding regions 1145:1227 The genome also contains an unusual distribution of tracts of 5 to 11 successive A or T nucleotides in intergenic domains between the mostly much higher GC content protein coding regions. 27340695 0 46 theme First 73:77 arg1 Sequence 16:23 Complete Genome Sequence 0:23 Complete Genome Sequence of Elephant Endotheliotropic Herpesvirus 4 0:66 Complete Genome Sequence of Elephant Endotheliotropic Herpesvirus 4, the First Example of a GC-Rich Branch Proboscivirus. 27340695 0 46 theme First 73:77 arg1 Example 79:85 the First Example 69:85 the First Example of a GC-Rich Branch Proboscivirus 69:119 Complete Genome Sequence of Elephant Endotheliotropic Herpesvirus 4, the First Example of a GC-Rich Branch Proboscivirus. 27340695 1 47 theme DNA 149:151 arg1 viruses 153:159 mammalian DNA viruses 139:159 mammalian DNA viruses called elephant endotheliotropic herpesviruses (EEHVs) belonging to the Proboscivirus genus 139:251 A novel group of mammalian DNA viruses called elephant endotheliotropic herpesviruses (EEHVs) belonging to the Proboscivirus genus has been associated with nearly 100 cases of highly lethal acute hemorrhagic disease in young Asian elephants worldwide. 27340695 8 48 link O-linked 1473:1480 arg1 vOGT 1513:1516 vOGT 1513:1516 vOGT 1513:1516 There are also two novel captured cellular genes, including a C-type lectin (vECTL) and an O-linked acetylglucosamine transferase (vOGT), as well as an unusually large and complex Ori-Lyt dyad symmetry domain. 27340695 8 48 link O-linked 1473:1480 arg1 transferase 1500:1510 an O-linked acetylglucosamine transferase 1470:1510 an O-linked acetylglucosamine transferase (vOGT) 1470:1517 There are also two novel captured cellular genes, including a C-type lectin (vECTL) and an O-linked acetylglucosamine transferase (vOGT), as well as an unusually large and complex Ori-Lyt dyad symmetry domain. 27340695 12 49 theme strain 2368:2373 arg1 sequence 2354:2361 the complete genomic DNA sequence 2329:2361 the complete genomic DNA sequence of a strain of EEHV4 obtained from a trunk wash sample collected from a surviving Asian elephant calf undergoing asymptomatic shedding during convalescence after an acute hemorrhagic disease episode 2329:2560 Here, we have determined the complete genomic DNA sequence of a strain of EEHV4 obtained from a trunk wash sample collected from a surviving Asian elephant calf undergoing asymptomatic shedding during convalescence after an acute hemorrhagic disease episode. 27340695 4 50 theme 206-kb 699:704 arg1 genome 706:711 the complete 206-kb genome 686:711 the complete 206-kb genome of EEHV4(Baylor) directly from trunk wash DNA 686:757 Here, we determined the complete 206-kb genome of EEHV4(Baylor) directly from trunk wash DNA by next-generation sequencing and de novo assembly procedures. 27340695 1 51 theme Asian 347:351 arg1 elephants 353:361 Asian elephants 347:361 young Asian elephants worldwide 341:371 A novel group of mammalian DNA viruses called elephant endotheliotropic herpesviruses (EEHVs) belonging to the Proboscivirus genus has been associated with nearly 100 cases of highly lethal acute hemorrhagic disease in young Asian elephants worldwide. 27340695 5 52 theme similar 887:893 arg1 organization 874:885 an overall colinear organization 854:885 an overall colinear organization similar to those of the AT-rich EEHVs 854:923 Among a total of 119 genes with an overall colinear organization similar to those of the AT-rich EEHVs, major features of EEHV4 include a family of 26 paralogous 7xTM and vGPCR-like genes plus 25 novel or missing genes. 27340695 1 53 theme novel 124:128 arg1 viruses 153:159 mammalian DNA viruses 139:159 mammalian DNA viruses called elephant endotheliotropic herpesviruses (EEHVs) belonging to the Proboscivirus genus 139:251 A novel group of mammalian DNA viruses called elephant endotheliotropic herpesviruses (EEHVs) belonging to the Proboscivirus genus has been associated with nearly 100 cases of highly lethal acute hemorrhagic disease in young Asian elephants worldwide. 27340695 1 53 theme novel 124:128 arg1 group 130:134 A novel group 122:134 A novel group of mammalian DNA viruses called elephant endotheliotropic herpesviruses (EEHVs) belonging to the Proboscivirus genus 122:251 A novel group of mammalian DNA viruses called elephant endotheliotropic herpesviruses (EEHVs) belonging to the Proboscivirus genus has been associated with nearly 100 cases of highly lethal acute hemorrhagic disease in young Asian elephants worldwide. 27340695 12 54 theme EEHV4 2378:2382 arg1 strain 2368:2373 a strain 2366:2373 a strain of EEHV4 obtained from a trunk wash sample collected from a surviving Asian elephant calf undergoing asymptomatic shedding during convalescence after an acute hemorrhagic disease episode 2366:2560 Here, we have determined the complete genomic DNA sequence of a strain of EEHV4 obtained from a trunk wash sample collected from a surviving Asian elephant calf undergoing asymptomatic shedding during convalescence after an acute hemorrhagic disease episode. 27340695 3 55 from EEHV4 563:567 arg1 kb 527:528 less than 6 kb 515:528 less than 6 kb of DNA sequence each from EEHV3, EEHV4, and EEHV7 515:578 However, less than 6 kb of DNA sequence each from EEHV3, EEHV4, and EEHV7 showed them to be a hugely diverged second major branch with GC-rich characteristics. 27340695 3 55 from EEHV4 563:567 arg1 sequence 537:544 DNA sequence 533:544 DNA sequence each from EEHV3, EEHV4, and EEHV7 533:578 However, less than 6 kb of DNA sequence each from EEHV3, EEHV4, and EEHV7 showed them to be a hugely diverged second major branch with GC-rich characteristics. 27340695 0 56 theme GC-Rich 92:98 arg1 Proboscivirus 107:119 a GC-Rich Branch Proboscivirus 90:119 a GC-Rich Branch Proboscivirus 90:119 Complete Genome Sequence of Elephant Endotheliotropic Herpesvirus 4, the First Example of a GC-Rich Branch Proboscivirus. 27340695 5 57 theme genes 1004:1008 arg1 family 960:965 a family 958:965 a family of 26 paralogous 7xTM and vGPCR-like genes plus 25 novel or missing genes 958:1039 Among a total of 119 genes with an overall colinear organization similar to those of the AT-rich EEHVs, major features of EEHV4 include a family of 26 paralogous 7xTM and vGPCR-like genes plus 25 novel or missing genes. 27340695 10 58 from lineages 1807:1814 arg1 herpesviruses 1772:1784 herpesviruses 1772:1784 herpesviruses from three different lineages of the Proboscivirus genus (EEHV1/6, EEHV2/5, and EEHV3/4/7) 1772:1875 IMPORTANCE Multiple species of herpesviruses from three different lineages of the Proboscivirus genus (EEHV1/6, EEHV2/5, and EEHV3/4/7) infect both Asian and African elephants, but lethal hemorrhagic disease is largely confined to Asian elephant calves and is predominantly associated with EEHV1. 27340695 10 58 from lineages 1807:1814 arg1 species 1761:1767 IMPORTANCE Multiple species 1741:1767 IMPORTANCE Multiple species of herpesviruses from three different lineages of the Proboscivirus genus (EEHV1/6, EEHV2/5, and EEHV3/4/7) 1741:1875 IMPORTANCE Multiple species of herpesviruses from three different lineages of the Proboscivirus genus (EEHV1/6, EEHV2/5, and EEHV3/4/7) infect both Asian and African elephants, but lethal hemorrhagic disease is largely confined to Asian elephant calves and is predominantly associated with EEHV1. 27340695 9 59 theme second 1614:1619 arg1 strain 1621:1626 a second strain 1612:1626 a second strain 1612:1626 Finally, 30 kb from a second strain proved to include three small chimeric domains, indicating the existence of distinct EEHV4A and EEHV4B subtypes. 27340695 11 60 theme Proboscivirus 2283:2295 arg1 genus 2297:2301 the Proboscivirus genus 2279:2301 the Proboscivirus genus 2279:2301 Milder disease caused by EEHV5 or EEHV4 is being increasingly recognized as well, but little is known about the latter, which is estimated to have diverged at least 35 million years ago from the others within a distinctive GC-rich branch of the Proboscivirus genus. 27340695 12 61 theme DNA 2350:2352 arg1 sequence 2354:2361 the complete genomic DNA sequence 2329:2361 the complete genomic DNA sequence of a strain of EEHV4 obtained from a trunk wash sample collected from a surviving Asian elephant calf undergoing asymptomatic shedding during convalescence after an acute hemorrhagic disease episode 2329:2560 Here, we have determined the complete genomic DNA sequence of a strain of EEHV4 obtained from a trunk wash sample collected from a surviving Asian elephant calf undergoing asymptomatic shedding during convalescence after an acute hemorrhagic disease episode. 27340695 2 62 theme complete 378:385 arg1 genomes 394:400 The complete 180-kb genomes 374:400 The complete 180-kb genomes of prototype strains from three AT-rich branch viruses, EEHV1A, EEHV1B, and EEHV5, 374:483 The complete 180-kb genomes of prototype strains from three AT-rich branch viruses, EEHV1A, EEHV1B, and EEHV5, have been published. 27340695 0 63 theme Complete 0:7 arg1 Sequence 16:23 Complete Genome Sequence 0:23 Complete Genome Sequence of Elephant Endotheliotropic Herpesvirus 4 0:66 Complete Genome Sequence of Elephant Endotheliotropic Herpesvirus 4, the First Example of a GC-Rich Branch Proboscivirus. 27340695 0 63 theme Complete 0:7 arg1 Example 79:85 the First Example 69:85 the First Example of a GC-Rich Branch Proboscivirus 69:119 Complete Genome Sequence of Elephant Endotheliotropic Herpesvirus 4, the First Example of a GC-Rich Branch Proboscivirus. 27340695 2 64 theme AT-rich 434:440 arg1 EEHV5 478:482 EEHV5 478:482 EEHV5 478:482 The complete 180-kb genomes of prototype strains from three AT-rich branch viruses, EEHV1A, EEHV1B, and EEHV5, have been published. 27340695 2 64 theme AT-rich 434:440 arg1 EEHV1A 458:463 EEHV1A 458:463 EEHV1A 458:463 The complete 180-kb genomes of prototype strains from three AT-rich branch viruses, EEHV1A, EEHV1B, and EEHV5, have been published. 27340695 2 64 theme AT-rich 434:440 arg1 viruses 449:455 three AT-rich branch viruses 428:455 three AT-rich branch viruses 428:455 The complete 180-kb genomes of prototype strains from three AT-rich branch viruses, EEHV1A, EEHV1B, and EEHV5, have been published. 27340695 2 64 theme AT-rich 434:440 arg1 EEHV1B 466:471 EEHV1B 466:471 EEHV1B 466:471 The complete 180-kb genomes of prototype strains from three AT-rich branch viruses, EEHV1A, EEHV1B, and EEHV5, have been published. 27340695 8 65 theme novel 1401:1405 arg1 genes 1425:1429 two novel captured cellular genes 1397:1429 two novel captured cellular genes 1397:1429 There are also two novel captured cellular genes, including a C-type lectin (vECTL) and an O-linked acetylglucosamine transferase (vOGT), as well as an unusually large and complex Ori-Lyt dyad symmetry domain. 27340695 5 66 theme colinear 865:872 arg1 organization 874:885 an overall colinear organization 854:885 an overall colinear organization similar to those of the AT-rich EEHVs 854:923 Among a total of 119 genes with an overall colinear organization similar to those of the AT-rich EEHVs, major features of EEHV4 include a family of 26 paralogous 7xTM and vGPCR-like genes plus 25 novel or missing genes. 27340695 8 67 theme cellular 1416:1423 arg1 genes 1425:1429 two novel captured cellular genes 1397:1429 two novel captured cellular genes 1397:1429 There are also two novel captured cellular genes, including a C-type lectin (vECTL) and an O-linked acetylglucosamine transferase (vOGT), as well as an unusually large and complex Ori-Lyt dyad symmetry domain. 27340695 3 68 from EEHV3 556:560 arg1 kb 527:528 less than 6 kb 515:528 less than 6 kb of DNA sequence each from EEHV3, EEHV4, and EEHV7 515:578 However, less than 6 kb of DNA sequence each from EEHV3, EEHV4, and EEHV7 showed them to be a hugely diverged second major branch with GC-rich characteristics. 27340695 3 68 from EEHV3 556:560 arg1 sequence 537:544 DNA sequence 533:544 DNA sequence each from EEHV3, EEHV4, and EEHV7 533:578 However, less than 6 kb of DNA sequence each from EEHV3, EEHV4, and EEHV7 showed them to be a hugely diverged second major branch with GC-rich characteristics. 27340695 2 69 theme prototype 405:413 arg1 strains 415:421 prototype strains 405:421 prototype strains from three AT-rich branch viruses, EEHV1A, EEHV1B, and EEHV5, 405:483 The complete 180-kb genomes of prototype strains from three AT-rich branch viruses, EEHV1A, EEHV1B, and EEHV5, have been published. 27340695 3 70 dep sequence 537:544 arg1 each 546:549 each 546:549 each 546:549 However, less than 6 kb of DNA sequence each from EEHV3, EEHV4, and EEHV7 showed them to be a hugely diverged second major branch with GC-rich characteristics. 27340695 5 71 theme genes 1035:1039 arg1 family 960:965 a family 958:965 a family of 26 paralogous 7xTM and vGPCR-like genes plus 25 novel or missing genes 958:1039 Among a total of 119 genes with an overall colinear organization similar to those of the AT-rich EEHVs, major features of EEHV4 include a family of 26 paralogous 7xTM and vGPCR-like genes plus 25 novel or missing genes. 27340695 0 72 theme Elephant 28:35 arg1 Herpesvirus 54:64 Elephant Endotheliotropic Herpesvirus 4 28:66 Elephant Endotheliotropic Herpesvirus 4 28:66 Complete Genome Sequence of Elephant Endotheliotropic Herpesvirus 4, the First Example of a GC-Rich Branch Proboscivirus. 27340695 5 73 theme major 926:930 arg1 features 932:939 major features 926:939 major features of EEHV4 926:948 Among a total of 119 genes with an overall colinear organization similar to those of the AT-rich EEHVs, major features of EEHV4 include a family of 26 paralogous 7xTM and vGPCR-like genes plus 25 novel or missing genes. 27340695 9 74 theme small 1652:1656 arg1 domains 1667:1673 three small chimeric domains 1646:1673 three small chimeric domains 1646:1673 Finally, 30 kb from a second strain proved to include three small chimeric domains, indicating the existence of distinct EEHV4A and EEHV4B subtypes. 27340695 4 75 theme wash 750:753 arg1 DNA 755:757 trunk wash DNA 744:757 trunk wash DNA 744:757 Here, we determined the complete 206-kb genome of EEHV4(Baylor) directly from trunk wash DNA by next-generation sequencing and de novo assembly procedures. 27340695 10 76 theme Multiple 1752:1759 arg1 species 1761:1767 IMPORTANCE Multiple species 1741:1767 IMPORTANCE Multiple species of herpesviruses from three different lineages of the Proboscivirus genus (EEHV1/6, EEHV2/5, and EEHV3/4/7) 1741:1875 IMPORTANCE Multiple species of herpesviruses from three different lineages of the Proboscivirus genus (EEHV1/6, EEHV2/5, and EEHV3/4/7) infect both Asian and African elephants, but lethal hemorrhagic disease is largely confined to Asian elephant calves and is predominantly associated with EEHV1. 27340695 1 77 from disease 330:336 arg1 worldwide 363:371 young Asian elephants worldwide 341:371 young Asian elephants worldwide 341:371 A novel group of mammalian DNA viruses called elephant endotheliotropic herpesviruses (EEHVs) belonging to the Proboscivirus genus has been associated with nearly 100 cases of highly lethal acute hemorrhagic disease in young Asian elephants worldwide. 27340695 1 78 theme lethal 305:310 arg1 disease 330:336 highly lethal acute hemorrhagic disease 298:336 highly lethal acute hemorrhagic disease in young Asian elephants worldwide 298:371 A novel group of mammalian DNA viruses called elephant endotheliotropic herpesviruses (EEHVs) belonging to the Proboscivirus genus has been associated with nearly 100 cases of highly lethal acute hemorrhagic disease in young Asian elephants worldwide. 27340695 1 79 from cases 289:293 arg1 worldwide 363:371 young Asian elephants worldwide 341:371 young Asian elephants worldwide 341:371 A novel group of mammalian DNA viruses called elephant endotheliotropic herpesviruses (EEHVs) belonging to the Proboscivirus genus has been associated with nearly 100 cases of highly lethal acute hemorrhagic disease in young Asian elephants worldwide. 27340695 2 80 from genomes 394:400 arg1 EEHV5 478:482 EEHV5 478:482 EEHV5 478:482 The complete 180-kb genomes of prototype strains from three AT-rich branch viruses, EEHV1A, EEHV1B, and EEHV5, have been published. 27340695 2 80 from genomes 394:400 arg1 EEHV1A 458:463 EEHV1A 458:463 EEHV1A 458:463 The complete 180-kb genomes of prototype strains from three AT-rich branch viruses, EEHV1A, EEHV1B, and EEHV5, have been published. 27340695 2 80 from genomes 394:400 arg1 viruses 449:455 three AT-rich branch viruses 428:455 three AT-rich branch viruses 428:455 The complete 180-kb genomes of prototype strains from three AT-rich branch viruses, EEHV1A, EEHV1B, and EEHV5, have been published. 27340695 2 80 from genomes 394:400 arg1 EEHV1B 466:471 EEHV1B 466:471 EEHV1B 466:471 The complete 180-kb genomes of prototype strains from three AT-rich branch viruses, EEHV1A, EEHV1B, and EEHV5, have been published. 27340695 10 81 theme Asian 1889:1893 arg1 elephants 1907:1915 both Asian and African elephants 1884:1915 both Asian and African elephants 1884:1915 IMPORTANCE Multiple species of herpesviruses from three different lineages of the Proboscivirus genus (EEHV1/6, EEHV2/5, and EEHV3/4/7) infect both Asian and African elephants, but lethal hemorrhagic disease is largely confined to Asian elephant calves and is predominantly associated with EEHV1. 27340695 3 82 theme diverged 607:614 arg1 branch 629:634 a hugely diverged second major branch 598:634 a hugely diverged second major branch with GC-rich characteristics 598:663 However, less than 6 kb of DNA sequence each from EEHV3, EEHV4, and EEHV7 showed them to be a hugely diverged second major branch with GC-rich characteristics. 27340695 14 83 theme distinctive 2706:2716 arg1 features 2718:2725 Several distinctive features 2698:2725 Several distinctive features of EEHV4 compared to AT-rich branch genomes 2698:2769 Several distinctive features of EEHV4 compared to AT-rich branch genomes are described. 27340695 11 84 theme GC-rich 2261:2267 arg1 branch 2269:2274 a distinctive GC-rich branch 2247:2274 a distinctive GC-rich branch of the Proboscivirus genus 2247:2301 Milder disease caused by EEHV5 or EEHV4 is being increasingly recognized as well, but little is known about the latter, which is estimated to have diverged at least 35 million years ago from the others within a distinctive GC-rich branch of the Proboscivirus genus. 27340695 12 85 theme genomic 2342:2348 arg1 sequence 2354:2361 the complete genomic DNA sequence 2329:2361 the complete genomic DNA sequence of a strain of EEHV4 obtained from a trunk wash sample collected from a surviving Asian elephant calf undergoing asymptomatic shedding during convalescence after an acute hemorrhagic disease episode 2329:2560 Here, we have determined the complete genomic DNA sequence of a strain of EEHV4 obtained from a trunk wash sample collected from a surviving Asian elephant calf undergoing asymptomatic shedding during convalescence after an acute hemorrhagic disease episode. 27340695 6 86 contain contains 1058:1065 arg2 distribution 1078:1089 an unusual distribution 1067:1089 an unusual distribution of tracts of 5 to 11 successive A or T nucleotides in intergenic domains between the mostly much higher GC content protein coding regions 1067:1227 The genome also contains an unusual distribution of tracts of 5 to 11 successive A or T nucleotides in intergenic domains between the mostly much higher GC content protein coding regions. 27340695 6 86 contain contains 1058:1065 arg1 genome 1046:1051 The genome 1042:1051 The genome 1042:1051 The genome also contains an unusual distribution of tracts of 5 to 11 successive A or T nucleotides in intergenic domains between the mostly much higher GC content protein coding regions. 27340695 7 87 theme many 1355:1358 arg1 proteins 1372:1379 many but not all proteins 1355:1379 many but not all proteins 1355:1379 Furthermore, an extremely high GC-rich bias in the third wobble position of codons clearly delineates the coding regions for many but not all proteins. 27340695 10 88 theme lethal 1922:1927 arg1 disease 1941:1947 lethal hemorrhagic disease 1922:1947 lethal hemorrhagic disease 1922:1947 IMPORTANCE Multiple species of herpesviruses from three different lineages of the Proboscivirus genus (EEHV1/6, EEHV2/5, and EEHV3/4/7) infect both Asian and African elephants, but lethal hemorrhagic disease is largely confined to Asian elephant calves and is predominantly associated with EEHV1. 27340695 5 89 theme novel 1018:1022 arg1 genes 1035:1039 25 novel or missing genes 1015:1039 25 novel or missing genes 1015:1039 Among a total of 119 genes with an overall colinear organization similar to those of the AT-rich EEHVs, major features of EEHV4 include a family of 26 paralogous 7xTM and vGPCR-like genes plus 25 novel or missing genes. 27340695 12 90 theme hemorrhagic 2534:2544 arg1 episode 2554:2560 an acute hemorrhagic disease episode 2525:2560 an acute hemorrhagic disease episode 2525:2560 Here, we have determined the complete genomic DNA sequence of a strain of EEHV4 obtained from a trunk wash sample collected from a surviving Asian elephant calf undergoing asymptomatic shedding during convalescence after an acute hemorrhagic disease episode. 27340695 9 91 theme distinct 1704:1711 arg1 subtypes 1731:1738 distinct EEHV4A and EEHV4B subtypes 1704:1738 distinct EEHV4A and EEHV4B subtypes 1704:1738 Finally, 30 kb from a second strain proved to include three small chimeric domains, indicating the existence of distinct EEHV4A and EEHV4B subtypes. 27340695 3 92 from EEHV7 574:578 arg1 kb 527:528 less than 6 kb 515:528 less than 6 kb of DNA sequence each from EEHV3, EEHV4, and EEHV7 515:578 However, less than 6 kb of DNA sequence each from EEHV3, EEHV4, and EEHV7 showed them to be a hugely diverged second major branch with GC-rich characteristics. 27340695 3 92 from EEHV7 574:578 arg1 sequence 537:544 DNA sequence 533:544 DNA sequence each from EEHV3, EEHV4, and EEHV7 533:578 However, less than 6 kb of DNA sequence each from EEHV3, EEHV4, and EEHV7 showed them to be a hugely diverged second major branch with GC-rich characteristics. 27340695 3 93 theme major 623:627 arg1 branch 629:634 a hugely diverged second major branch 598:634 a hugely diverged second major branch with GC-rich characteristics 598:663 However, less than 6 kb of DNA sequence each from EEHV3, EEHV4, and EEHV7 showed them to be a hugely diverged second major branch with GC-rich characteristics. 27340695 6 94 theme intergenic 1145:1154 arg1 domains 1156:1162 intergenic domains 1145:1162 intergenic domains between the mostly much higher GC content protein coding regions 1145:1227 The genome also contains an unusual distribution of tracts of 5 to 11 successive A or T nucleotides in intergenic domains between the mostly much higher GC content protein coding regions. 27340695 7 95 theme codons 1306:1311 arg1 position 1294:1301 the third wobble position 1277:1301 the third wobble position of codons 1277:1311 Furthermore, an extremely high GC-rich bias in the third wobble position of codons clearly delineates the coding regions for many but not all proteins. 27340695 8 96 theme O-linked 1473:1480 arg1 vOGT 1513:1516 vOGT 1513:1516 vOGT 1513:1516 There are also two novel captured cellular genes, including a C-type lectin (vECTL) and an O-linked acetylglucosamine transferase (vOGT), as well as an unusually large and complex Ori-Lyt dyad symmetry domain. 27340695 8 96 theme O-linked 1473:1480 arg1 transferase 1500:1510 an O-linked acetylglucosamine transferase 1470:1510 an O-linked acetylglucosamine transferase (vOGT) 1470:1517 There are also two novel captured cellular genes, including a C-type lectin (vECTL) and an O-linked acetylglucosamine transferase (vOGT), as well as an unusually large and complex Ori-Lyt dyad symmetry domain. 27340695 6 97 theme nucleotides 1130:1140 arg1 tracts 1094:1099 tracts 1094:1099 tracts of 5 to 11 successive A or T nucleotides 1094:1140 The genome also contains an unusual distribution of tracts of 5 to 11 successive A or T nucleotides in intergenic domains between the mostly much higher GC content protein coding regions. 27340695 1 98 theme viruses 153:159 arg1 viruses 153:159 mammalian DNA viruses 139:159 mammalian DNA viruses called elephant endotheliotropic herpesviruses (EEHVs) belonging to the Proboscivirus genus 139:251 A novel group of mammalian DNA viruses called elephant endotheliotropic herpesviruses (EEHVs) belonging to the Proboscivirus genus has been associated with nearly 100 cases of highly lethal acute hemorrhagic disease in young Asian elephants worldwide. 27340695 1 98 theme viruses 153:159 arg1 group 130:134 A novel group 122:134 A novel group of mammalian DNA viruses called elephant endotheliotropic herpesviruses (EEHVs) belonging to the Proboscivirus genus 122:251 A novel group of mammalian DNA viruses called elephant endotheliotropic herpesviruses (EEHVs) belonging to the Proboscivirus genus has been associated with nearly 100 cases of highly lethal acute hemorrhagic disease in young Asian elephants worldwide. 27340695 0 99 theme Herpesvirus 54:64 arg1 Sequence 16:23 Complete Genome Sequence 0:23 Complete Genome Sequence of Elephant Endotheliotropic Herpesvirus 4 0:66 Complete Genome Sequence of Elephant Endotheliotropic Herpesvirus 4, the First Example of a GC-Rich Branch Proboscivirus. 27340695 0 99 theme Herpesvirus 54:64 arg1 Example 79:85 the First Example 69:85 the First Example of a GC-Rich Branch Proboscivirus 69:119 Complete Genome Sequence of Elephant Endotheliotropic Herpesvirus 4, the First Example of a GC-Rich Branch Proboscivirus. 27340695 9 100 theme subtypes 1731:1738 arg1 existence 1691:1699 the existence 1687:1699 the existence of distinct EEHV4A and EEHV4B subtypes 1687:1738 Finally, 30 kb from a second strain proved to include three small chimeric domains, indicating the existence of distinct EEHV4A and EEHV4B subtypes. 27340695 10 101 theme IMPORTANCE 1741:1750 arg1 species 1761:1767 IMPORTANCE Multiple species 1741:1767 IMPORTANCE Multiple species of herpesviruses from three different lineages of the Proboscivirus genus (EEHV1/6, EEHV2/5, and EEHV3/4/7) 1741:1875 IMPORTANCE Multiple species of herpesviruses from three different lineages of the Proboscivirus genus (EEHV1/6, EEHV2/5, and EEHV3/4/7) infect both Asian and African elephants, but lethal hemorrhagic disease is largely confined to Asian elephant calves and is predominantly associated with EEHV1. 27340695 14 102 theme EEHV4 2730:2734 arg1 features 2718:2725 Several distinctive features 2698:2725 Several distinctive features of EEHV4 compared to AT-rich branch genomes 2698:2769 Several distinctive features of EEHV4 compared to AT-rich branch genomes are described. 27340695 8 103 theme large 1544:1548 arg1 domain 1584:1589 an unusually large and complex Ori-Lyt dyad symmetry domain 1531:1589 an unusually large and complex Ori-Lyt dyad symmetry domain 1531:1589 There are also two novel captured cellular genes, including a C-type lectin (vECTL) and an O-linked acetylglucosamine transferase (vOGT), as well as an unusually large and complex Ori-Lyt dyad symmetry domain. 27340695 1 104 theme elephant 168:175 arg1 EEHVs 209:213 EEHVs 209:213 EEHVs 209:213 A novel group of mammalian DNA viruses called elephant endotheliotropic herpesviruses (EEHVs) belonging to the Proboscivirus genus has been associated with nearly 100 cases of highly lethal acute hemorrhagic disease in young Asian elephants worldwide. 27340695 1 104 theme elephant 168:175 arg1 herpesviruses 194:206 elephant endotheliotropic herpesviruses 168:206 elephant endotheliotropic herpesviruses (EEHVs) belonging to the Proboscivirus genus 168:251 A novel group of mammalian DNA viruses called elephant endotheliotropic herpesviruses (EEHVs) belonging to the Proboscivirus genus has been associated with nearly 100 cases of highly lethal acute hemorrhagic disease in young Asian elephants worldwide. 27340695 11 105 theme distinctive 2249:2259 arg1 branch 2269:2274 a distinctive GC-rich branch 2247:2274 a distinctive GC-rich branch of the Proboscivirus genus 2247:2301 Milder disease caused by EEHV5 or EEHV4 is being increasingly recognized as well, but little is known about the latter, which is estimated to have diverged at least 35 million years ago from the others within a distinctive GC-rich branch of the Proboscivirus genus. 27340695 4 106 theme next-generation 762:776 arg1 sequencing 778:787 next-generation sequencing 762:787 next-generation sequencing 762:787 Here, we determined the complete 206-kb genome of EEHV4(Baylor) directly from trunk wash DNA by next-generation sequencing and de novo assembly procedures. 27340695 7 107 theme third 1281:1285 arg1 position 1294:1301 the third wobble position 1277:1301 the third wobble position of codons 1277:1311 Furthermore, an extremely high GC-rich bias in the third wobble position of codons clearly delineates the coding regions for many but not all proteins. 27340695 6 108 theme coding 1214:1219 arg1 regions 1221:1227 protein coding regions 1206:1227 the mostly much higher GC content protein coding regions 1172:1227 The genome also contains an unusual distribution of tracts of 5 to 11 successive A or T nucleotides in intergenic domains between the mostly much higher GC content protein coding regions. 27340695 8 109 theme complex 1554:1560 arg1 domain 1584:1589 an unusually large and complex Ori-Lyt dyad symmetry domain 1531:1589 an unusually large and complex Ori-Lyt dyad symmetry domain 1531:1589 There are also two novel captured cellular genes, including a C-type lectin (vECTL) and an O-linked acetylglucosamine transferase (vOGT), as well as an unusually large and complex Ori-Lyt dyad symmetry domain. 27340695 10 110 theme herpesviruses 1772:1784 arg1 species 1761:1767 IMPORTANCE Multiple species 1741:1767 IMPORTANCE Multiple species of herpesviruses from three different lineages of the Proboscivirus genus (EEHV1/6, EEHV2/5, and EEHV3/4/7) 1741:1875 IMPORTANCE Multiple species of herpesviruses from three different lineages of the Proboscivirus genus (EEHV1/6, EEHV2/5, and EEHV3/4/7) infect both Asian and African elephants, but lethal hemorrhagic disease is largely confined to Asian elephant calves and is predominantly associated with EEHV1. 27340695 14 111 theme Several 2698:2704 arg1 features 2718:2725 Several distinctive features 2698:2725 Several distinctive features of EEHV4 compared to AT-rich branch genomes 2698:2769 Several distinctive features of EEHV4 compared to AT-rich branch genomes are described. 27340695 8 112 theme dyad 1570:1573 arg1 domain 1584:1589 an unusually large and complex Ori-Lyt dyad symmetry domain 1531:1589 an unusually large and complex Ori-Lyt dyad symmetry domain 1531:1589 There are also two novel captured cellular genes, including a C-type lectin (vECTL) and an O-linked acetylglucosamine transferase (vOGT), as well as an unusually large and complex Ori-Lyt dyad symmetry domain. 27340695 7 113 theme GC-rich 1261:1267 arg1 bias 1269:1272 an extremely high GC-rich bias 1243:1272 an extremely high GC-rich bias in the third wobble position of codons 1243:1311 Furthermore, an extremely high GC-rich bias in the third wobble position of codons clearly delineates the coding regions for many but not all proteins. 27340695 6 114 theme higher 1188:1193 arg1 content 1198:1204 the mostly much higher GC content protein coding regions 1172:1227 the mostly much higher GC content protein coding regions 1172:1227 The genome also contains an unusual distribution of tracts of 5 to 11 successive A or T nucleotides in intergenic domains between the mostly much higher GC content protein coding regions. 27340695 5 115 theme 7xTM 984:987 arg1 genes 1004:1008 26 paralogous 7xTM and vGPCR-like genes 970:1008 26 paralogous 7xTM and vGPCR-like genes 970:1008 Among a total of 119 genes with an overall colinear organization similar to those of the AT-rich EEHVs, major features of EEHV4 include a family of 26 paralogous 7xTM and vGPCR-like genes plus 25 novel or missing genes. 27340695 3 116 theme sequence 537:544 arg1 kb 527:528 less than 6 kb 515:528 less than 6 kb of DNA sequence each from EEHV3, EEHV4, and EEHV7 515:578 However, less than 6 kb of DNA sequence each from EEHV3, EEHV4, and EEHV7 showed them to be a hugely diverged second major branch with GC-rich characteristics. 27340695 5 117 theme missing 1027:1033 arg1 genes 1035:1039 25 novel or missing genes 1015:1039 25 novel or missing genes 1015:1039 Among a total of 119 genes with an overall colinear organization similar to those of the AT-rich EEHVs, major features of EEHV4 include a family of 26 paralogous 7xTM and vGPCR-like genes plus 25 novel or missing genes. 27340695 12 118 theme surviving 2435:2443 arg1 elephant 2451:2458 a surviving Asian elephant 2433:2458 a surviving Asian elephant calf undergoing asymptomatic shedding during convalescence 2433:2517 Here, we have determined the complete genomic DNA sequence of a strain of EEHV4 obtained from a trunk wash sample collected from a surviving Asian elephant calf undergoing asymptomatic shedding during convalescence after an acute hemorrhagic disease episode. 27340695 10 119 theme elephant 1978:1985 arg1 calves 1987:1992 Asian elephant calves 1972:1992 Asian elephant calves 1972:1992 IMPORTANCE Multiple species of herpesviruses from three different lineages of the Proboscivirus genus (EEHV1/6, EEHV2/5, and EEHV3/4/7) infect both Asian and African elephants, but lethal hemorrhagic disease is largely confined to Asian elephant calves and is predominantly associated with EEHV1. 27340695 5 120 theme 119 839:841 arg1 genes 843:847 119 genes 839:847 119 genes with an overall colinear organization similar to those of the AT-rich EEHVs 839:923 Among a total of 119 genes with an overall colinear organization similar to those of the AT-rich EEHVs, major features of EEHV4 include a family of 26 paralogous 7xTM and vGPCR-like genes plus 25 novel or missing genes. 27340695 12 121 theme elephant 2451:2458 arg1 calf 2460:2463 a surviving Asian elephant calf 2433:2463 a surviving Asian elephant calf undergoing asymptomatic shedding during convalescence 2433:2517 Here, we have determined the complete genomic DNA sequence of a strain of EEHV4 obtained from a trunk wash sample collected from a surviving Asian elephant calf undergoing asymptomatic shedding during convalescence after an acute hemorrhagic disease episode. 27340695 6 122 theme tracts 1094:1099 arg1 distribution 1078:1089 an unusual distribution 1067:1089 an unusual distribution of tracts of 5 to 11 successive A or T nucleotides in intergenic domains between the mostly much higher GC content protein coding regions 1067:1227 The genome also contains an unusual distribution of tracts of 5 to 11 successive A or T nucleotides in intergenic domains between the mostly much higher GC content protein coding regions. 27340695 13 123 theme known 2618:2622 arg1 species 2653:2659 the three known GC-rich branch Proboscivirus species 2608:2659 the three known GC-rich branch Proboscivirus species 2608:2659 This represents the first example from among the three known GC-rich branch Proboscivirus species to be assembled and fully annotated. 27340695 12 124 theme wash 2406:2409 arg1 sample 2411:2416 a trunk wash sample 2398:2416 a trunk wash sample collected from a surviving Asian elephant calf undergoing asymptomatic shedding during convalescence after an acute hemorrhagic disease episode 2398:2560 Here, we have determined the complete genomic DNA sequence of a strain of EEHV4 obtained from a trunk wash sample collected from a surviving Asian elephant calf undergoing asymptomatic shedding during convalescence after an acute hemorrhagic disease episode. 27340695 10 125 theme genus 1837:1841 arg1 lineages 1807:1814 three different lineages 1791:1814 three different lineages of the Proboscivirus genus (EEHV1/6, EEHV2/5, and EEHV3/4/7) 1791:1875 IMPORTANCE Multiple species of herpesviruses from three different lineages of the Proboscivirus genus (EEHV1/6, EEHV2/5, and EEHV3/4/7) infect both Asian and African elephants, but lethal hemorrhagic disease is largely confined to Asian elephant calves and is predominantly associated with EEHV1. 27340695 1 126 theme disease 330:336 arg1 cases 289:293 nearly 100 cases 278:293 nearly 100 cases of highly lethal acute hemorrhagic disease in young Asian elephants worldwide 278:371 A novel group of mammalian DNA viruses called elephant endotheliotropic herpesviruses (EEHVs) belonging to the Proboscivirus genus has been associated with nearly 100 cases of highly lethal acute hemorrhagic disease in young Asian elephants worldwide. 27340695 13 127 theme branch 2632:2637 arg1 species 2653:2659 the three known GC-rich branch Proboscivirus species 2608:2659 the three known GC-rich branch Proboscivirus species 2608:2659 This represents the first example from among the three known GC-rich branch Proboscivirus species to be assembled and fully annotated. 27340695 1 128 theme mammalian 139:147 arg1 viruses 153:159 mammalian DNA viruses 139:159 mammalian DNA viruses called elephant endotheliotropic herpesviruses (EEHVs) belonging to the Proboscivirus genus 139:251 A novel group of mammalian DNA viruses called elephant endotheliotropic herpesviruses (EEHVs) belonging to the Proboscivirus genus has been associated with nearly 100 cases of highly lethal acute hemorrhagic disease in young Asian elephants worldwide. 27340695 6 129 theme protein 1206:1212 arg1 regions 1221:1227 protein coding regions 1206:1227 the mostly much higher GC content protein coding regions 1172:1227 The genome also contains an unusual distribution of tracts of 5 to 11 successive A or T nucleotides in intergenic domains between the mostly much higher GC content protein coding regions. 27340695 2 130 from viruses 449:455 arg1 genomes 394:400 The complete 180-kb genomes 374:400 The complete 180-kb genomes of prototype strains from three AT-rich branch viruses, EEHV1A, EEHV1B, and EEHV5, 374:483 The complete 180-kb genomes of prototype strains from three AT-rich branch viruses, EEHV1A, EEHV1B, and EEHV5, have been published. 27340695 2 130 from viruses 449:455 arg1 strains 415:421 prototype strains 405:421 prototype strains from three AT-rich branch viruses, EEHV1A, EEHV1B, and EEHV5, 405:483 The complete 180-kb genomes of prototype strains from three AT-rich branch viruses, EEHV1A, EEHV1B, and EEHV5, have been published. 27340695 6 131 dep 11 1109:1110 arg1 to 1106:1107 to 1106:1107 to 1106:1107 The genome also contains an unusual distribution of tracts of 5 to 11 successive A or T nucleotides in intergenic domains between the mostly much higher GC content protein coding regions. 27340695 1 132 theme young 341:345 arg1 worldwide 363:371 young Asian elephants worldwide 341:371 young Asian elephants worldwide 341:371 A novel group of mammalian DNA viruses called elephant endotheliotropic herpesviruses (EEHVs) belonging to the Proboscivirus genus has been associated with nearly 100 cases of highly lethal acute hemorrhagic disease in young Asian elephants worldwide. 27340695 4 133 from genome 706:711 arg1 DNA 755:757 trunk wash DNA 744:757 trunk wash DNA 744:757 Here, we determined the complete 206-kb genome of EEHV4(Baylor) directly from trunk wash DNA by next-generation sequencing and de novo assembly procedures. 27340695 11 134 theme genus 2297:2301 arg1 branch 2269:2274 a distinctive GC-rich branch 2247:2274 a distinctive GC-rich branch of the Proboscivirus genus 2247:2301 Milder disease caused by EEHV5 or EEHV4 is being increasingly recognized as well, but little is known about the latter, which is estimated to have diverged at least 35 million years ago from the others within a distinctive GC-rich branch of the Proboscivirus genus. 27340695 4 135 theme complete 690:697 arg1 genome 706:711 the complete 206-kb genome 686:711 the complete 206-kb genome of EEHV4(Baylor) directly from trunk wash DNA 686:757 Here, we determined the complete 206-kb genome of EEHV4(Baylor) directly from trunk wash DNA by next-generation sequencing and de novo assembly procedures. 27340695 0 136 theme Branch 100:105 arg1 Proboscivirus 107:119 a GC-Rich Branch Proboscivirus 90:119 a GC-Rich Branch Proboscivirus 90:119 Complete Genome Sequence of Elephant Endotheliotropic Herpesvirus 4, the First Example of a GC-Rich Branch Proboscivirus. 27340695 1 137 theme elephants 353:361 arg1 worldwide 363:371 young Asian elephants worldwide 341:371 young Asian elephants worldwide 341:371 A novel group of mammalian DNA viruses called elephant endotheliotropic herpesviruses (EEHVs) belonging to the Proboscivirus genus has been associated with nearly 100 cases of highly lethal acute hemorrhagic disease in young Asian elephants worldwide. 27340695 5 138 with genes 843:847 arg1 organization 874:885 an overall colinear organization 854:885 an overall colinear organization similar to those of the AT-rich EEHVs 854:923 Among a total of 119 genes with an overall colinear organization similar to those of the AT-rich EEHVs, major features of EEHV4 include a family of 26 paralogous 7xTM and vGPCR-like genes plus 25 novel or missing genes. 27340695 2 139 theme 180-kb 387:392 arg1 genomes 394:400 The complete 180-kb genomes 374:400 The complete 180-kb genomes of prototype strains from three AT-rich branch viruses, EEHV1A, EEHV1B, and EEHV5, 374:483 The complete 180-kb genomes of prototype strains from three AT-rich branch viruses, EEHV1A, EEHV1B, and EEHV5, have been published. 27340695 0 140 theme Genome 9:14 arg1 Sequence 16:23 Complete Genome Sequence 0:23 Complete Genome Sequence of Elephant Endotheliotropic Herpesvirus 4 0:66 Complete Genome Sequence of Elephant Endotheliotropic Herpesvirus 4, the First Example of a GC-Rich Branch Proboscivirus. 27340695 0 140 theme Genome 9:14 arg1 Example 79:85 the First Example 69:85 the First Example of a GC-Rich Branch Proboscivirus 69:119 Complete Genome Sequence of Elephant Endotheliotropic Herpesvirus 4, the First Example of a GC-Rich Branch Proboscivirus. 27340695 4 141 from DNA 755:757 arg1 Baylor 722:727 Baylor 722:727 Baylor 722:727 Here, we determined the complete 206-kb genome of EEHV4(Baylor) directly from trunk wash DNA by next-generation sequencing and de novo assembly procedures. 27340695 4 141 from DNA 755:757 arg1 EEHV4 716:720 EEHV4 716:720 EEHV4(Baylor) directly from trunk wash DNA 716:757 Here, we determined the complete 206-kb genome of EEHV4(Baylor) directly from trunk wash DNA by next-generation sequencing and de novo assembly procedures. 27340695 4 141 from DNA 755:757 arg1 genome 706:711 the complete 206-kb genome 686:711 the complete 206-kb genome of EEHV4(Baylor) directly from trunk wash DNA 686:757 Here, we determined the complete 206-kb genome of EEHV4(Baylor) directly from trunk wash DNA by next-generation sequencing and de novo assembly procedures. 27340695 5 142 theme vGPCR-like 993:1002 arg1 genes 1004:1008 26 paralogous 7xTM and vGPCR-like genes 970:1008 26 paralogous 7xTM and vGPCR-like genes 970:1008 Among a total of 119 genes with an overall colinear organization similar to those of the AT-rich EEHVs, major features of EEHV4 include a family of 26 paralogous 7xTM and vGPCR-like genes plus 25 novel or missing genes. 27340695 2 143 theme branch 442:447 arg1 EEHV5 478:482 EEHV5 478:482 EEHV5 478:482 The complete 180-kb genomes of prototype strains from three AT-rich branch viruses, EEHV1A, EEHV1B, and EEHV5, have been published. 27340695 2 143 theme branch 442:447 arg1 EEHV1A 458:463 EEHV1A 458:463 EEHV1A 458:463 The complete 180-kb genomes of prototype strains from three AT-rich branch viruses, EEHV1A, EEHV1B, and EEHV5, have been published. 27340695 2 143 theme branch 442:447 arg1 viruses 449:455 three AT-rich branch viruses 428:455 three AT-rich branch viruses 428:455 The complete 180-kb genomes of prototype strains from three AT-rich branch viruses, EEHV1A, EEHV1B, and EEHV5, have been published. 27340695 2 143 theme branch 442:447 arg1 EEHV1B 466:471 EEHV1B 466:471 EEHV1B 466:471 The complete 180-kb genomes of prototype strains from three AT-rich branch viruses, EEHV1A, EEHV1B, and EEHV5, have been published. 27340695 8 144 theme captured 1407:1414 arg1 genes 1425:1429 two novel captured cellular genes 1397:1429 two novel captured cellular genes 1397:1429 There are also two novel captured cellular genes, including a C-type lectin (vECTL) and an O-linked acetylglucosamine transferase (vOGT), as well as an unusually large and complex Ori-Lyt dyad symmetry domain. 27340695 13 145 theme first 2583:2587 arg1 example 2589:2595 the first example 2579:2595 the first example from among the three known GC-rich branch Proboscivirus species to be assembled and fully annotated 2579:2695 This represents the first example from among the three known GC-rich branch Proboscivirus species to be assembled and fully annotated. 27340695 5 146 theme overall 857:863 arg1 organization 874:885 an overall colinear organization 854:885 an overall colinear organization similar to those of the AT-rich EEHVs 854:923 Among a total of 119 genes with an overall colinear organization similar to those of the AT-rich EEHVs, major features of EEHV4 include a family of 26 paralogous 7xTM and vGPCR-like genes plus 25 novel or missing genes. 27340695 7 147 theme high 1256:1259 arg1 bias 1269:1272 an extremely high GC-rich bias 1243:1272 an extremely high GC-rich bias in the third wobble position of codons 1243:1311 Furthermore, an extremely high GC-rich bias in the third wobble position of codons clearly delineates the coding regions for many but not all proteins. 27340695 2 148 theme strains 415:421 arg1 genomes 394:400 The complete 180-kb genomes 374:400 The complete 180-kb genomes of prototype strains from three AT-rich branch viruses, EEHV1A, EEHV1B, and EEHV5, 374:483 The complete 180-kb genomes of prototype strains from three AT-rich branch viruses, EEHV1A, EEHV1B, and EEHV5, have been published. 27340695 0 149 theme Endotheliotropic 37:52 arg1 Herpesvirus 54:64 Elephant Endotheliotropic Herpesvirus 4 28:66 Elephant Endotheliotropic Herpesvirus 4 28:66 Complete Genome Sequence of Elephant Endotheliotropic Herpesvirus 4, the First Example of a GC-Rich Branch Proboscivirus. 27340695 4 150 dep de 793:794 arg1 novo 796:799 novo 796:799 novo 796:799 Here, we determined the complete 206-kb genome of EEHV4(Baylor) directly from trunk wash DNA by next-generation sequencing and de novo assembly procedures. 27340695 9 151 theme chimeric 1658:1665 arg1 domains 1667:1673 three small chimeric domains 1646:1673 three small chimeric domains 1646:1673 Finally, 30 kb from a second strain proved to include three small chimeric domains, indicating the existence of distinct EEHV4A and EEHV4B subtypes. 27340695 8 152 theme C-type 1444:1449 arg1 vECTL 1459:1463 vECTL 1459:1463 vECTL 1459:1463 There are also two novel captured cellular genes, including a C-type lectin (vECTL) and an O-linked acetylglucosamine transferase (vOGT), as well as an unusually large and complex Ori-Lyt dyad symmetry domain. 27340695 8 152 theme C-type 1444:1449 arg1 lectin 1451:1456 a C-type lectin 1442:1456 a C-type lectin (vECTL) 1442:1464 There are also two novel captured cellular genes, including a C-type lectin (vECTL) and an O-linked acetylglucosamine transferase (vOGT), as well as an unusually large and complex Ori-Lyt dyad symmetry domain. 27340695 4 153 theme trunk 744:748 arg1 DNA 755:757 trunk wash DNA 744:757 trunk wash DNA 744:757 Here, we determined the complete 206-kb genome of EEHV4(Baylor) directly from trunk wash DNA by next-generation sequencing and de novo assembly procedures. 27340695 1 154 theme acute 312:316 arg1 disease 330:336 highly lethal acute hemorrhagic disease 298:336 highly lethal acute hemorrhagic disease in young Asian elephants worldwide 298:371 A novel group of mammalian DNA viruses called elephant endotheliotropic herpesviruses (EEHVs) belonging to the Proboscivirus genus has been associated with nearly 100 cases of highly lethal acute hemorrhagic disease in young Asian elephants worldwide. 27340695 4 155 theme EEHV4 716:720 arg1 genome 706:711 the complete 206-kb genome 686:711 the complete 206-kb genome of EEHV4(Baylor) directly from trunk wash DNA 686:757 Here, we determined the complete 206-kb genome of EEHV4(Baylor) directly from trunk wash DNA by next-generation sequencing and de novo assembly procedures. 27340695 7 156 theme all 1368:1370 arg1 proteins 1372:1379 many but not all proteins 1355:1379 many but not all proteins 1355:1379 Furthermore, an extremely high GC-rich bias in the third wobble position of codons clearly delineates the coding regions for many but not all proteins. 27340695 5 157 theme AT-rich 911:917 arg1 EEHVs 919:923 the AT-rich EEHVs 907:923 the AT-rich EEHVs 907:923 Among a total of 119 genes with an overall colinear organization similar to those of the AT-rich EEHVs, major features of EEHV4 include a family of 26 paralogous 7xTM and vGPCR-like genes plus 25 novel or missing genes. 27340695 12 158 theme complete 2333:2340 arg1 sequence 2354:2361 the complete genomic DNA sequence 2329:2361 the complete genomic DNA sequence of a strain of EEHV4 obtained from a trunk wash sample collected from a surviving Asian elephant calf undergoing asymptomatic shedding during convalescence after an acute hemorrhagic disease episode 2329:2560 Here, we have determined the complete genomic DNA sequence of a strain of EEHV4 obtained from a trunk wash sample collected from a surviving Asian elephant calf undergoing asymptomatic shedding during convalescence after an acute hemorrhagic disease episode. 27340695 1 159 from worldwide 363:371 arg1 cases 289:293 nearly 100 cases 278:293 nearly 100 cases of highly lethal acute hemorrhagic disease in young Asian elephants worldwide 278:371 A novel group of mammalian DNA viruses called elephant endotheliotropic herpesviruses (EEHVs) belonging to the Proboscivirus genus has been associated with nearly 100 cases of highly lethal acute hemorrhagic disease in young Asian elephants worldwide. 27340695 1 160 theme Proboscivirus 233:245 arg1 genus 247:251 the Proboscivirus genus 229:251 the Proboscivirus genus 229:251 A novel group of mammalian DNA viruses called elephant endotheliotropic herpesviruses (EEHVs) belonging to the Proboscivirus genus has been associated with nearly 100 cases of highly lethal acute hemorrhagic disease in young Asian elephants worldwide. 27224859 0 0 theme viruses 82:88 arg1 subgenotypes 20:31 two new subgenotypes 12:31 two new subgenotypes of porcine reproductive and respiratory syndrome viruses in Southeast China 12:107 Emerging of two new subgenotypes of porcine reproductive and respiratory syndrome viruses in Southeast China. 27224859 9 1 theme different 1015:1023 arg1 patterns 1029:1036 different NGS patterns 1015:1036 different NGS patterns 1015:1036 This indicates that the two new subgenotypes of PRRSV strains with different NGS patterns were spreading in those regions of China. 27224859 3 2 theme Nsp2 440:443 arg1 genes 445:449 some Nsp2 genes 435:449 some Nsp2 genes 435:449 All the ORF5 genes and some Nsp2 genes were sequenced. 27224859 7 3 theme site 814:817 arg1 patterns 825:832 13 putative N-linked glycosylation site (NGS) patterns 779:832 13 putative N-linked glycosylation site (NGS) patterns 779:832 These isolates formed 13 putative N-linked glycosylation site (NGS) patterns based on N30, 33, 34, 35, 44 and 51. 27224859 9 4 with subgenotypes 980:991 arg1 patterns 1029:1036 different NGS patterns 1015:1036 different NGS patterns 1015:1036 This indicates that the two new subgenotypes of PRRSV strains with different NGS patterns were spreading in those regions of China. 27224859 0 5 theme syndrome 73:80 arg1 viruses 82:88 porcine reproductive and respiratory syndrome viruses 36:88 porcine reproductive and respiratory syndrome viruses 36:88 Emerging of two new subgenotypes of porcine reproductive and respiratory syndrome viruses in Southeast China. 27224859 2 6 dep 2015 406:409 arg1 to 403:404 to 403:404 to 403:404 In this study, a total of 49 PRRSV isolates were collected from different swine herds in seven provinces in Southeast China from 2014 to 2015. 27224859 9 7 theme NGS 1025:1027 arg1 patterns 1029:1036 different NGS patterns 1015:1036 different NGS patterns 1015:1036 This indicates that the two new subgenotypes of PRRSV strains with different NGS patterns were spreading in those regions of China. 27224859 2 8 theme isolates 304:311 arg1 total 286:290 a total 284:290 a total of 49 PRRSV isolates 284:311 In this study, a total of 49 PRRSV isolates were collected from different swine herds in seven provinces in Southeast China from 2014 to 2015. 27224859 7 9 theme putative 782:789 arg1 patterns 825:832 13 putative N-linked glycosylation site (NGS) patterns 779:832 13 putative N-linked glycosylation site (NGS) patterns 779:832 These isolates formed 13 putative N-linked glycosylation site (NGS) patterns based on N30, 33, 34, 35, 44 and 51. 27224859 10 10 theme disease 1162:1168 arg1 control 1131:1137 control 1131:1137 control 1131:1137 The genetic diversity should be considered for the control and prevention of this disease. 27224859 10 10 theme disease 1162:1168 arg1 prevention 1143:1152 prevention 1143:1152 prevention 1143:1152 The genetic diversity should be considered for the control and prevention of this disease. 27224859 5 11 theme new 593:595 arg1 IV 609:610 a new subgenotype IV 591:610 a new subgenotype IV derived from highly pathogenic PRRSV (HP-PRRSV) 591:658 Among them, five isolates formed a new subgenotype IV derived from highly pathogenic PRRSV (HP-PRRSV). 27224859 6 12 theme NADC30 732:737 arg1 strain 739:744 the NADC30 strain 728:744 the NADC30 strain in the US 728:754 Six isolates formed subgenotype III, which were closely related to the NADC30 strain in the US. 27224859 7 13 theme N-linked 791:798 arg1 patterns 825:832 13 putative N-linked glycosylation site (NGS) patterns 779:832 13 putative N-linked glycosylation site (NGS) patterns 779:832 These isolates formed 13 putative N-linked glycosylation site (NGS) patterns based on N30, 33, 34, 35, 44 and 51. 27224859 4 14 theme North 534:538 arg1 genotype 548:555 the North America genotype 530:555 the North America genotype 530:555 Phylogenetic analysis showed that all the isolates belonged to the North America genotype. 27224859 9 15 theme PRRSV 996:1000 arg1 strains 1002:1008 PRRSV strains 996:1008 PRRSV strains 996:1008 This indicates that the two new subgenotypes of PRRSV strains with different NGS patterns were spreading in those regions of China. 27224859 5 16 theme subgenotype 597:607 arg1 IV 609:610 a new subgenotype IV 591:610 a new subgenotype IV derived from highly pathogenic PRRSV (HP-PRRSV) 591:658 Among them, five isolates formed a new subgenotype IV derived from highly pathogenic PRRSV (HP-PRRSV). 27224859 7 17 link N-linked 791:798 arg1 patterns 825:832 13 putative N-linked glycosylation site (NGS) patterns 779:832 13 putative N-linked glycosylation site (NGS) patterns 779:832 These isolates formed 13 putative N-linked glycosylation site (NGS) patterns based on N30, 33, 34, 35, 44 and 51. 27224859 1 18 theme global 246:251 arg1 industry 259:266 the global swine industry 242:266 the global swine industry 242:266 Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the leading swine pathogens and causes major economic loss to the global swine industry. 27224859 2 19 from 2015 406:409 arg1 provinces 364:372 seven provinces 358:372 seven provinces in Southeast China from 2014 to 2015 358:409 In this study, a total of 49 PRRSV isolates were collected from different swine herds in seven provinces in Southeast China from 2014 to 2015. 27224859 6 20 from strain 739:744 arg1 US 753:754 US 753:754 US 753:754 Six isolates formed subgenotype III, which were closely related to the NADC30 strain in the US. 27224859 0 21 from subgenotypes 20:31 arg1 China 103:107 China 103:107 China 103:107 Emerging of two new subgenotypes of porcine reproductive and respiratory syndrome viruses in Southeast China. 27224859 2 22 theme swine 343:347 arg1 herds 349:353 different swine herds 333:353 different swine herds in seven provinces in Southeast China from 2014 to 2015 333:409 In this study, a total of 49 PRRSV isolates were collected from different swine herds in seven provinces in Southeast China from 2014 to 2015. 27224859 1 23 theme swine 253:257 arg1 industry 259:266 the global swine industry 242:266 the global swine industry 242:266 Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the leading swine pathogens and causes major economic loss to the global swine industry. 27224859 5 24 attach derived 612:618 arg2 IV 609:610 a new subgenotype IV 591:610 a new subgenotype IV derived from highly pathogenic PRRSV (HP-PRRSV) 591:658 Among them, five isolates formed a new subgenotype IV derived from highly pathogenic PRRSV (HP-PRRSV). 27224859 5 24 attach derived 612:618 arg1 HP-PRRSV 650:657 HP-PRRSV 650:657 HP-PRRSV 650:657 Among them, five isolates formed a new subgenotype IV derived from highly pathogenic PRRSV (HP-PRRSV). 27224859 5 24 attach derived 612:618 arg1 PRRSV 643:647 highly pathogenic PRRSV 625:647 highly pathogenic PRRSV (HP-PRRSV) 625:658 Among them, five isolates formed a new subgenotype IV derived from highly pathogenic PRRSV (HP-PRRSV). 27224859 2 25 theme different 333:341 arg1 herds 349:353 different swine herds 333:353 different swine herds in seven provinces in Southeast China from 2014 to 2015 333:409 In this study, a total of 49 PRRSV isolates were collected from different swine herds in seven provinces in Southeast China from 2014 to 2015. 27224859 0 26 theme new 16:18 arg1 subgenotypes 20:31 two new subgenotypes 12:31 two new subgenotypes of porcine reproductive and respiratory syndrome viruses in Southeast China 12:107 Emerging of two new subgenotypes of porcine reproductive and respiratory syndrome viruses in Southeast China. 27224859 5 27 theme pathogenic 632:641 arg1 PRRSV 643:647 highly pathogenic PRRSV 625:647 highly pathogenic PRRSV (HP-PRRSV) 625:658 Among them, five isolates formed a new subgenotype IV derived from highly pathogenic PRRSV (HP-PRRSV). 27224859 5 27 theme pathogenic 632:641 arg1 HP-PRRSV 650:657 HP-PRRSV 650:657 HP-PRRSV 650:657 Among them, five isolates formed a new subgenotype IV derived from highly pathogenic PRRSV (HP-PRRSV). 27224859 10 28 dep control 1131:1137 arg1 the 1127:1129 the 1127:1129 the 1127:1129 The genetic diversity should be considered for the control and prevention of this disease. 27224859 9 29 theme China 1073:1077 arg1 regions 1062:1068 those regions 1056:1068 those regions of China 1056:1077 This indicates that the two new subgenotypes of PRRSV strains with different NGS patterns were spreading in those regions of China. 27224859 1 30 theme leading 184:190 arg1 pathogens 198:206 the leading swine pathogens 180:206 the leading swine pathogens 180:206 Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the leading swine pathogens and causes major economic loss to the global swine industry. 27224859 7 31 gly glycosylation 800:812 arg2 patterns 825:832 13 putative N-linked glycosylation site (NGS) patterns 779:832 13 putative N-linked glycosylation site (NGS) patterns 779:832 These isolates formed 13 putative N-linked glycosylation site (NGS) patterns based on N30, 33, 34, 35, 44 and 51. 27224859 7 31 gly glycosylation 800:812 arg2 site 814:817 13 putative N-linked glycosylation site (NGS) patterns 779:832 13 putative N-linked glycosylation site (NGS) patterns 779:832 These isolates formed 13 putative N-linked glycosylation site (NGS) patterns based on N30, 33, 34, 35, 44 and 51. 27224859 8 32 theme fewer 882:886 arg1 NGSs 888:891 fewer NGSs 882:891 fewer NGSs of isolates 882:903 There were fewer NGSs of isolates in subgenotype IV than in subgenotype III. 27224859 1 33 theme swine 192:196 arg1 pathogens 198:206 the leading swine pathogens 180:206 the leading swine pathogens 180:206 Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the leading swine pathogens and causes major economic loss to the global swine industry. 27224859 4 34 theme Phylogenetic 467:478 arg1 analysis 480:487 Phylogenetic analysis 467:487 Phylogenetic analysis 467:487 Phylogenetic analysis showed that all the isolates belonged to the North America genotype. 27224859 1 35 theme pathogens 198:206 arg1 one 173:175 one 173:175 one 173:175 Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the leading swine pathogens and causes major economic loss to the global swine industry. 27224859 1 35 theme pathogens 198:206 arg1 pathogens 198:206 the leading swine pathogens 180:206 the leading swine pathogens 180:206 Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the leading swine pathogens and causes major economic loss to the global swine industry. 27224859 0 36 theme reproductive 44:55 arg1 viruses 82:88 porcine reproductive and respiratory syndrome viruses 36:88 porcine reproductive and respiratory syndrome viruses 36:88 Emerging of two new subgenotypes of porcine reproductive and respiratory syndrome viruses in Southeast China. 27224859 9 37 theme new 976:978 arg1 subgenotypes 980:991 the two new subgenotypes 968:991 the two new subgenotypes of PRRSV strains with different NGS patterns 968:1036 This indicates that the two new subgenotypes of PRRSV strains with different NGS patterns were spreading in those regions of China. 27224859 9 37 theme new 976:978 arg1 spreading 1043:1051 spreading 1043:1051 spreading 1043:1051 This indicates that the two new subgenotypes of PRRSV strains with different NGS patterns were spreading in those regions of China. 27224859 2 38 theme PRRSV 298:302 arg1 isolates 304:311 49 PRRSV isolates 295:311 49 PRRSV isolates 295:311 In this study, a total of 49 PRRSV isolates were collected from different swine herds in seven provinces in Southeast China from 2014 to 2015. 27224859 8 39 theme isolates 896:903 arg1 NGSs 888:891 fewer NGSs 882:891 fewer NGSs of isolates 882:903 There were fewer NGSs of isolates in subgenotype IV than in subgenotype III. 27224859 10 40 theme genetic 1084:1090 arg1 diversity 1092:1100 The genetic diversity 1080:1100 The genetic diversity 1080:1100 The genetic diversity should be considered for the control and prevention of this disease. 27224859 2 41 from herds 349:353 arg1 provinces 364:372 seven provinces 358:372 seven provinces in Southeast China from 2014 to 2015 358:409 In this study, a total of 49 PRRSV isolates were collected from different swine herds in seven provinces in Southeast China from 2014 to 2015. 27224859 3 42 theme ORF5 420:423 arg1 genes 425:429 All the ORF5 genes 412:429 All the ORF5 genes 412:429 All the ORF5 genes and some Nsp2 genes were sequenced. 27224859 2 43 from provinces 364:372 arg1 China 387:391 China 387:391 China 387:391 In this study, a total of 49 PRRSV isolates were collected from different swine herds in seven provinces in Southeast China from 2014 to 2015. 27224859 2 43 from provinces 364:372 arg1 2015 406:409 2015 406:409 2015 406:409 In this study, a total of 49 PRRSV isolates were collected from different swine herds in seven provinces in Southeast China from 2014 to 2015. 27224859 1 44 theme respiratory 135:145 arg1 virus 156:160 Porcine reproductive and respiratory syndrome virus 110:160 virus 156:160 Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the leading swine pathogens and causes major economic loss to the global swine industry. 27224859 4 45 theme America 540:546 arg1 genotype 548:555 the North America genotype 530:555 the North America genotype 530:555 Phylogenetic analysis showed that all the isolates belonged to the North America genotype. 27224859 0 46 theme respiratory 61:71 arg1 viruses 82:88 porcine reproductive and respiratory syndrome viruses 36:88 porcine reproductive and respiratory syndrome viruses 36:88 Emerging of two new subgenotypes of porcine reproductive and respiratory syndrome viruses in Southeast China. 27224859 9 47 theme strains 1002:1008 arg1 subgenotypes 980:991 the two new subgenotypes 968:991 the two new subgenotypes of PRRSV strains with different NGS patterns 968:1036 This indicates that the two new subgenotypes of PRRSV strains with different NGS patterns were spreading in those regions of China. 27224859 9 47 theme strains 1002:1008 arg1 spreading 1043:1051 spreading 1043:1051 spreading 1043:1051 This indicates that the two new subgenotypes of PRRSV strains with different NGS patterns were spreading in those regions of China. 27224859 1 48 theme syndrome 147:154 arg1 virus 156:160 Porcine reproductive and respiratory syndrome virus 110:160 virus 156:160 Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the leading swine pathogens and causes major economic loss to the global swine industry. 27224859 7 49 theme NGS 820:822 arg1 patterns 825:832 13 putative N-linked glycosylation site (NGS) patterns 779:832 13 putative N-linked glycosylation site (NGS) patterns 779:832 These isolates formed 13 putative N-linked glycosylation site (NGS) patterns based on N30, 33, 34, 35, 44 and 51. 27224859 1 50 theme major 219:223 arg1 loss 234:237 major economic loss 219:237 major economic loss to the global swine industry 219:266 Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the leading swine pathogens and causes major economic loss to the global swine industry. 27224859 9 51 from spreading 1043:1051 arg1 regions 1062:1068 those regions 1056:1068 those regions of China 1056:1077 This indicates that the two new subgenotypes of PRRSV strains with different NGS patterns were spreading in those regions of China. 27224859 7 52 theme glycosylation 800:812 arg1 patterns 825:832 13 putative N-linked glycosylation site (NGS) patterns 779:832 13 putative N-linked glycosylation site (NGS) patterns 779:832 These isolates formed 13 putative N-linked glycosylation site (NGS) patterns based on N30, 33, 34, 35, 44 and 51. 27224859 1 53 theme economic 225:232 arg1 loss 234:237 major economic loss 219:237 major economic loss to the global swine industry 219:266 Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the leading swine pathogens and causes major economic loss to the global swine industry. 26809064 6 0 theme intermediate 779:790 arg1 mannan 795:800 high and intermediate Mw mannan 770:800 high and intermediate Mw mannan 770:800 GPC-MALLS revealed a reduction in high and intermediate Mw mannan by 85% in GOA31. 26809064 1 1 theme Candida 143:149 arg1 albicans 151:158 Candida albicans 143:158 Candida albicans 143:158 The Goa1p of Candida albicans regulates mitochondrial Complex I (CI) activities in its role as a putative CI accessory protein. 26809064 9 2 theme mitochondrial 1023:1035 arg1 production 1047:1056 mitochondrial CI energy production 1023:1056 mitochondrial CI energy production 1023:1056 We conclude that mitochondrial CI energy production is highly integrated with cell wall formation. 26809064 1 3 theme albicans 151:158 arg1 Goa1p 134:138 The Goa1p 130:138 The Goa1p of Candida albicans 130:158 The Goa1p of Candida albicans regulates mitochondrial Complex I (CI) activities in its role as a putative CI accessory protein. 26809064 1 4 theme putative 227:234 arg1 protein 249:255 a putative CI accessory protein 225:255 a putative CI accessory protein 225:255 The Goa1p of Candida albicans regulates mitochondrial Complex I (CI) activities in its role as a putative CI accessory protein. 26809064 0 5 theme Complex 99:105 arg1 Regulator 72:80 a Putative Regulator 61:80 a Putative Regulator of Mitochondrial Complex I in Candida albicans 61:127 Cell Wall N-Linked Mannoprotein Biosynthesis Requires Goa1p, a Putative Regulator of Mitochondrial Complex I in Candida albicans. 26809064 0 5 theme Complex 99:105 arg1 Goa1p 54:58 Goa1p 54:58 Goa1p 54:58 Cell Wall N-Linked Mannoprotein Biosynthesis Requires Goa1p, a Putative Regulator of Mitochondrial Complex I in Candida albicans. 26809064 8 6 theme -linked 906:912 arg1 chains 926:931 β-(1,6)-linked glucan side chains 899:931 β-(1,6)-linked glucan side chains 899:931 β-(1,6)-linked glucan side chains were branched about twice as often but were shorter in length for GOA31. 26809064 7 7 theme α-mannosyl 853:862 arg1 linkages 864:871 β-mannosyl but not α-mannosyl linkages 834:871 β-mannosyl but not α-mannosyl linkages 834:871 A reduction of β-mannosyl but not α-mannosyl linkages was noted in GOA31 cells. 26809064 1 8 theme CI 236:237 arg1 protein 249:255 a putative CI accessory protein 225:255 a putative CI accessory protein 225:255 The Goa1p of Candida albicans regulates mitochondrial Complex I (CI) activities in its role as a putative CI accessory protein. 26809064 0 9 theme Mitochondrial 85:97 arg1 Complex 99:105 Mitochondrial Complex I 85:107 Mitochondrial Complex I 85:107 Cell Wall N-Linked Mannoprotein Biosynthesis Requires Goa1p, a Putative Regulator of Mitochondrial Complex I in Candida albicans. 26809064 7 10 theme β-mannosyl 834:843 arg1 linkages 864:871 β-mannosyl but not α-mannosyl linkages 834:871 β-mannosyl but not α-mannosyl linkages 834:871 A reduction of β-mannosyl but not α-mannosyl linkages was noted in GOA31 cells. 26809064 2 11 theme Transcriptional 258:272 arg1 profiling 274:282 Transcriptional profiling 258:282 Transcriptional profiling of goa1∆ 258:291 Transcriptional profiling of goa1∆ revealed a down regulation of genes encoding β-oligomannosyl transferases. 26809064 10 12 theme cell 1140:1143 arg1 processes 1163:1171 not all cell wall biosynthetic processes 1132:1171 not all cell wall biosynthetic processes 1132:1171 Our data also suggest that not all cell wall biosynthetic processes are dependent upon Goa1p even though it provides high levels of ATP to cells. 26809064 1 13 theme accessory 239:247 arg1 protein 249:255 a putative CI accessory protein 225:255 a putative CI accessory protein 225:255 The Goa1p of Candida albicans regulates mitochondrial Complex I (CI) activities in its role as a putative CI accessory protein. 26809064 11 14 theme subunit 1333:1339 arg1 proteins 1341:1348 CI subunit proteins 1330:1348 CI subunit proteins 1330:1348 The availability of both broadly conserved and fungal-specific mutants lacking CI subunit proteins should be useful in assessing functions of fungal-specific functions subunit proteins. 26809064 8 15 theme side 921:924 arg1 chains 926:931 β-(1,6)-linked glucan side chains 899:931 β-(1,6)-linked glucan side chains 899:931 β-(1,6)-linked glucan side chains were branched about twice as often but were shorter in length for GOA31. 26809064 11 16 theme conserved 1284:1292 arg1 mutants 1314:1320 both broadly conserved and fungal-specific mutants 1271:1320 both broadly conserved and fungal-specific mutants lacking CI subunit proteins 1271:1348 The availability of both broadly conserved and fungal-specific mutants lacking CI subunit proteins should be useful in assessing functions of fungal-specific functions subunit proteins. 26809064 3 17 theme goa1∆ 419:423 arg1 phenotypes 405:414 cell wall phenotypes 395:414 cell wall phenotypes of goa1∆ (strain GOA31) 395:438 Herein, we present data on cell wall phenotypes of goa1∆ (strain GOA31). 26809064 4 18 theme gene-reconstituted 530:547 arg1 GOA32 557:561 GOA32 557:561 GOA32 557:561 We used transmission electron microscopy (TEM), GPC/MALLS, and NMR to compare GOA31 to a gene-reconstituted strain (GOA32) and parental cells. 26809064 4 18 theme gene-reconstituted 530:547 arg1 strain 549:554 a gene-reconstituted strain 528:554 a gene-reconstituted strain (GOA32) 528:562 We used transmission electron microscopy (TEM), GPC/MALLS, and NMR to compare GOA31 to a gene-reconstituted strain (GOA32) and parental cells. 26809064 4 19 theme electron 462:469 arg1 TEM 483:485 TEM 483:485 TEM 483:485 We used transmission electron microscopy (TEM), GPC/MALLS, and NMR to compare GOA31 to a gene-reconstituted strain (GOA32) and parental cells. 26809064 4 19 theme electron 462:469 arg1 microscopy 471:480 transmission electron microscopy 449:480 transmission electron microscopy (TEM) 449:486 We used transmission electron microscopy (TEM), GPC/MALLS, and NMR to compare GOA31 to a gene-reconstituted strain (GOA32) and parental cells. 26809064 5 20 theme defined 687:693 arg1 layer 700:704 a defined wall layer 685:704 a defined wall layer close to the plasma membrane 685:733 We note by TEM a reduction in outer wall fibrils, increased inner wall transparency, and the loss of a defined wall layer close to the plasma membrane. 26809064 6 21 from reduction 757:765 arg1 mannan 795:800 high and intermediate Mw mannan 770:800 high and intermediate Mw mannan 770:800 GPC-MALLS revealed a reduction in high and intermediate Mw mannan by 85% in GOA31. 26809064 1 22 theme mitochondrial 170:182 arg1 Complex 184:190 mitochondrial Complex I 170:192 mitochondrial Complex I (CI) activities 170:208 The Goa1p of Candida albicans regulates mitochondrial Complex I (CI) activities in its role as a putative CI accessory protein. 26809064 1 22 theme mitochondrial 170:182 arg1 CI 195:196 CI 195:196 CI 195:196 The Goa1p of Candida albicans regulates mitochondrial Complex I (CI) activities in its role as a putative CI accessory protein. 26809064 0 23 theme Wall 5:8 arg1 Biosynthesis 32:43 Cell Wall N-Linked Mannoprotein Biosynthesis 0:43 Cell Wall N-Linked Mannoprotein Biosynthesis 0:43 Cell Wall N-Linked Mannoprotein Biosynthesis Requires Goa1p, a Putative Regulator of Mitochondrial Complex I in Candida albicans. 26809064 4 24 theme transmission 449:460 arg1 TEM 483:485 TEM 483:485 TEM 483:485 We used transmission electron microscopy (TEM), GPC/MALLS, and NMR to compare GOA31 to a gene-reconstituted strain (GOA32) and parental cells. 26809064 4 24 theme transmission 449:460 arg1 microscopy 471:480 transmission electron microscopy 449:480 transmission electron microscopy (TEM) 449:486 We used transmission electron microscopy (TEM), GPC/MALLS, and NMR to compare GOA31 to a gene-reconstituted strain (GOA32) and parental cells. 26809064 6 25 from % 807:807 arg1 GOA31 812:816 GOA31 812:816 GOA31 812:816 GPC-MALLS revealed a reduction in high and intermediate Mw mannan by 85% in GOA31. 26809064 1 26 theme Complex 184:190 arg1 activities 199:208 mitochondrial Complex I (CI) activities 170:208 mitochondrial Complex I (CI) activities 170:208 The Goa1p of Candida albicans regulates mitochondrial Complex I (CI) activities in its role as a putative CI accessory protein. 26809064 0 27 theme Cell 0:3 arg1 Biosynthesis 32:43 Cell Wall N-Linked Mannoprotein Biosynthesis 0:43 Cell Wall N-Linked Mannoprotein Biosynthesis 0:43 Cell Wall N-Linked Mannoprotein Biosynthesis Requires Goa1p, a Putative Regulator of Mitochondrial Complex I in Candida albicans. 26809064 11 28 theme subunit 1419:1425 arg1 proteins 1427:1434 fungal-specific functions subunit proteins 1393:1434 fungal-specific functions subunit proteins 1393:1434 The availability of both broadly conserved and fungal-specific mutants lacking CI subunit proteins should be useful in assessing functions of fungal-specific functions subunit proteins. 26809064 11 29 theme mutants 1314:1320 arg1 useful 1360:1365 useful 1360:1365 useful 1360:1365 The availability of both broadly conserved and fungal-specific mutants lacking CI subunit proteins should be useful in assessing functions of fungal-specific functions subunit proteins. 26809064 11 29 theme mutants 1314:1320 arg1 availability 1255:1266 The availability 1251:1266 The availability of both broadly conserved and fungal-specific mutants lacking CI subunit proteins 1251:1348 The availability of both broadly conserved and fungal-specific mutants lacking CI subunit proteins should be useful in assessing functions of fungal-specific functions subunit proteins. 26809064 6 30 theme high 770:773 arg1 mannan 795:800 high and intermediate Mw mannan 770:800 high and intermediate Mw mannan 770:800 GPC-MALLS revealed a reduction in high and intermediate Mw mannan by 85% in GOA31. 26809064 0 31 theme Mannoprotein 19:30 arg1 Biosynthesis 32:43 Cell Wall N-Linked Mannoprotein Biosynthesis 0:43 Cell Wall N-Linked Mannoprotein Biosynthesis 0:43 Cell Wall N-Linked Mannoprotein Biosynthesis Requires Goa1p, a Putative Regulator of Mitochondrial Complex I in Candida albicans. 26809064 11 32 theme proteins 1427:1434 arg1 functions 1380:1388 functions 1380:1388 functions of fungal-specific functions subunit proteins 1380:1434 The availability of both broadly conserved and fungal-specific mutants lacking CI subunit proteins should be useful in assessing functions of fungal-specific functions subunit proteins. 26809064 2 33 theme goa1∆ 287:291 arg1 profiling 274:282 Transcriptional profiling 258:282 Transcriptional profiling of goa1∆ 258:291 Transcriptional profiling of goa1∆ revealed a down regulation of genes encoding β-oligomannosyl transferases. 26809064 11 34 theme fungal-specific 1393:1407 arg1 proteins 1427:1434 fungal-specific functions subunit proteins 1393:1434 fungal-specific functions subunit proteins 1393:1434 The availability of both broadly conserved and fungal-specific mutants lacking CI subunit proteins should be useful in assessing functions of fungal-specific functions subunit proteins. 26809064 9 35 theme wall 1089:1092 arg1 formation 1094:1102 cell wall formation 1084:1102 cell wall formation 1084:1102 We conclude that mitochondrial CI energy production is highly integrated with cell wall formation. 26809064 0 36 theme N-Linked 10:17 arg1 Biosynthesis 32:43 Cell Wall N-Linked Mannoprotein Biosynthesis 0:43 Cell Wall N-Linked Mannoprotein Biosynthesis 0:43 Cell Wall N-Linked Mannoprotein Biosynthesis Requires Goa1p, a Putative Regulator of Mitochondrial Complex I in Candida albicans. 26809064 0 37 theme Candida 112:118 arg1 albicans 120:127 Candida albicans 112:127 Candida albicans 112:127 Cell Wall N-Linked Mannoprotein Biosynthesis Requires Goa1p, a Putative Regulator of Mitochondrial Complex I in Candida albicans. 26809064 9 38 theme cell 1084:1087 arg1 formation 1094:1102 cell wall formation 1084:1102 cell wall formation 1084:1102 We conclude that mitochondrial CI energy production is highly integrated with cell wall formation. 26809064 11 39 theme fungal-specific 1298:1312 arg1 mutants 1314:1320 both broadly conserved and fungal-specific mutants 1271:1320 both broadly conserved and fungal-specific mutants lacking CI subunit proteins 1271:1348 The availability of both broadly conserved and fungal-specific mutants lacking CI subunit proteins should be useful in assessing functions of fungal-specific functions subunit proteins. 26809064 10 40 theme biosynthetic 1150:1161 arg1 processes 1163:1171 not all cell wall biosynthetic processes 1132:1171 not all cell wall biosynthetic processes 1132:1171 Our data also suggest that not all cell wall biosynthetic processes are dependent upon Goa1p even though it provides high levels of ATP to cells. 26809064 4 41 theme parental 568:575 arg1 cells 577:581 parental cells 568:581 parental cells 568:581 We used transmission electron microscopy (TEM), GPC/MALLS, and NMR to compare GOA31 to a gene-reconstituted strain (GOA32) and parental cells. 26809064 3 42 theme cell 395:398 arg1 phenotypes 405:414 cell wall phenotypes 395:414 cell wall phenotypes of goa1∆ (strain GOA31) 395:438 Herein, we present data on cell wall phenotypes of goa1∆ (strain GOA31). 26809064 5 43 theme increased 634:642 arg1 transparency 655:666 increased inner wall transparency 634:666 increased inner wall transparency 634:666 We note by TEM a reduction in outer wall fibrils, increased inner wall transparency, and the loss of a defined wall layer close to the plasma membrane. 26809064 0 44 from Regulator 72:80 arg1 albicans 120:127 Candida albicans 112:127 Candida albicans 112:127 Cell Wall N-Linked Mannoprotein Biosynthesis Requires Goa1p, a Putative Regulator of Mitochondrial Complex I in Candida albicans. 26809064 5 45 theme inner 644:648 arg1 transparency 655:666 increased inner wall transparency 634:666 increased inner wall transparency 634:666 We note by TEM a reduction in outer wall fibrils, increased inner wall transparency, and the loss of a defined wall layer close to the plasma membrane. 26809064 10 46 theme wall 1145:1148 arg1 processes 1163:1171 not all cell wall biosynthetic processes 1132:1171 not all cell wall biosynthetic processes 1132:1171 Our data also suggest that not all cell wall biosynthetic processes are dependent upon Goa1p even though it provides high levels of ATP to cells. 26809064 3 47 theme strain 426:431 arg1 goa1∆ 419:423 goa1∆ 419:423 goa1∆ (strain GOA31) 419:438 Herein, we present data on cell wall phenotypes of goa1∆ (strain GOA31). 26809064 3 47 theme strain 426:431 arg1 GOA31 433:437 strain GOA31 426:437 strain GOA31 426:437 Herein, we present data on cell wall phenotypes of goa1∆ (strain GOA31). 26809064 3 48 theme wall 400:403 arg1 phenotypes 405:414 cell wall phenotypes 395:414 cell wall phenotypes of goa1∆ (strain GOA31) 395:438 Herein, we present data on cell wall phenotypes of goa1∆ (strain GOA31). 26809064 5 49 theme wall 695:698 arg1 layer 700:704 a defined wall layer 685:704 a defined wall layer close to the plasma membrane 685:733 We note by TEM a reduction in outer wall fibrils, increased inner wall transparency, and the loss of a defined wall layer close to the plasma membrane. 26809064 5 50 theme plasma 719:724 arg1 membrane 726:733 the plasma membrane 715:733 the plasma membrane 715:733 We note by TEM a reduction in outer wall fibrils, increased inner wall transparency, and the loss of a defined wall layer close to the plasma membrane. 26809064 5 51 theme layer 700:704 arg1 loss 677:680 the loss 673:680 the loss of a defined wall layer close to the plasma membrane 673:733 We note by TEM a reduction in outer wall fibrils, increased inner wall transparency, and the loss of a defined wall layer close to the plasma membrane. 26809064 5 51 theme layer 700:704 arg1 reduction 601:609 a reduction 599:609 a reduction in outer wall fibrils 599:631 We note by TEM a reduction in outer wall fibrils, increased inner wall transparency, and the loss of a defined wall layer close to the plasma membrane. 26809064 5 51 theme layer 700:704 arg1 transparency 655:666 increased inner wall transparency 634:666 increased inner wall transparency 634:666 We note by TEM a reduction in outer wall fibrils, increased inner wall transparency, and the loss of a defined wall layer close to the plasma membrane. 26809064 5 52 theme wall 650:653 arg1 transparency 655:666 increased inner wall transparency 634:666 increased inner wall transparency 634:666 We note by TEM a reduction in outer wall fibrils, increased inner wall transparency, and the loss of a defined wall layer close to the plasma membrane. 26809064 9 53 theme energy 1040:1045 arg1 production 1047:1056 mitochondrial CI energy production 1023:1056 mitochondrial CI energy production 1023:1056 We conclude that mitochondrial CI energy production is highly integrated with cell wall formation. 26809064 5 54 from transparency 655:666 arg1 fibrils 625:631 outer wall fibrils 614:631 outer wall fibrils 614:631 We note by TEM a reduction in outer wall fibrils, increased inner wall transparency, and the loss of a defined wall layer close to the plasma membrane. 26809064 6 55 theme Mw 792:793 arg1 mannan 795:800 high and intermediate Mw mannan 770:800 high and intermediate Mw mannan 770:800 GPC-MALLS revealed a reduction in high and intermediate Mw mannan by 85% in GOA31. 26809064 2 56 theme genes 323:327 arg1 regulation 309:318 a down regulation 302:318 a down regulation of genes encoding β-oligomannosyl transferases 302:365 Transcriptional profiling of goa1∆ revealed a down regulation of genes encoding β-oligomannosyl transferases. 26809064 4 57 used used 444:447 arg2 We 441:442 We 441:442 We 441:442 We used transmission electron microscopy (TEM), GPC/MALLS, and NMR to compare GOA31 to a gene-reconstituted strain (GOA32) and parental cells. 26809064 10 58 theme ATP 1237:1239 arg1 levels 1227:1232 high levels 1222:1232 high levels of ATP to cells 1222:1248 Our data also suggest that not all cell wall biosynthetic processes are dependent upon Goa1p even though it provides high levels of ATP to cells. 26809064 8 59 theme glucan 914:919 arg1 chains 926:931 β-(1,6)-linked glucan side chains 899:931 β-(1,6)-linked glucan side chains 899:931 β-(1,6)-linked glucan side chains were branched about twice as often but were shorter in length for GOA31. 26809064 7 60 theme GOA31 886:890 arg1 cells 892:896 GOA31 cells 886:896 GOA31 cells 886:896 A reduction of β-mannosyl but not α-mannosyl linkages was noted in GOA31 cells. 26809064 8 61 link -linked 906:912 arg1 chains 926:931 β-(1,6)-linked glucan side chains 899:931 β-(1,6)-linked glucan side chains 899:931 β-(1,6)-linked glucan side chains were branched about twice as often but were shorter in length for GOA31. 26809064 5 62 theme outer 614:618 arg1 fibrils 625:631 outer wall fibrils 614:631 outer wall fibrils 614:631 We note by TEM a reduction in outer wall fibrils, increased inner wall transparency, and the loss of a defined wall layer close to the plasma membrane. 26809064 9 63 theme CI 1037:1038 arg1 production 1047:1056 mitochondrial CI energy production 1023:1056 mitochondrial CI energy production 1023:1056 We conclude that mitochondrial CI energy production is highly integrated with cell wall formation. 26809064 5 64 theme wall 620:623 arg1 fibrils 625:631 outer wall fibrils 614:631 outer wall fibrils 614:631 We note by TEM a reduction in outer wall fibrils, increased inner wall transparency, and the loss of a defined wall layer close to the plasma membrane. 26809064 10 65 theme high 1222:1225 arg1 levels 1227:1232 high levels 1222:1232 high levels of ATP to cells 1222:1248 Our data also suggest that not all cell wall biosynthetic processes are dependent upon Goa1p even though it provides high levels of ATP to cells. 26809064 2 66 theme down 304:307 arg1 regulation 309:318 a down regulation 302:318 a down regulation of genes encoding β-oligomannosyl transferases 302:365 Transcriptional profiling of goa1∆ revealed a down regulation of genes encoding β-oligomannosyl transferases. 26809064 11 67 theme CI 1330:1331 arg1 proteins 1341:1348 CI subunit proteins 1330:1348 CI subunit proteins 1330:1348 The availability of both broadly conserved and fungal-specific mutants lacking CI subunit proteins should be useful in assessing functions of fungal-specific functions subunit proteins. 26809064 0 68 theme Putative 63:70 arg1 Regulator 72:80 a Putative Regulator 61:80 a Putative Regulator of Mitochondrial Complex I in Candida albicans 61:127 Cell Wall N-Linked Mannoprotein Biosynthesis Requires Goa1p, a Putative Regulator of Mitochondrial Complex I in Candida albicans. 26809064 0 68 theme Putative 63:70 arg1 Goa1p 54:58 Goa1p 54:58 Goa1p 54:58 Cell Wall N-Linked Mannoprotein Biosynthesis Requires Goa1p, a Putative Regulator of Mitochondrial Complex I in Candida albicans. 26809064 5 69 from loss 677:680 arg1 fibrils 625:631 outer wall fibrils 614:631 outer wall fibrils 614:631 We note by TEM a reduction in outer wall fibrils, increased inner wall transparency, and the loss of a defined wall layer close to the plasma membrane. 26809064 2 70 theme β-oligomannosyl 338:352 arg1 transferases 354:365 β-oligomannosyl transferases 338:365 β-oligomannosyl transferases 338:365 Transcriptional profiling of goa1∆ revealed a down regulation of genes encoding β-oligomannosyl transferases. 26809064 11 71 theme functions 1409:1417 arg1 proteins 1427:1434 fungal-specific functions subunit proteins 1393:1434 fungal-specific functions subunit proteins 1393:1434 The availability of both broadly conserved and fungal-specific mutants lacking CI subunit proteins should be useful in assessing functions of fungal-specific functions subunit proteins. 26809064 5 72 from reduction 601:609 arg1 fibrils 625:631 outer wall fibrils 614:631 outer wall fibrils 614:631 We note by TEM a reduction in outer wall fibrils, increased inner wall transparency, and the loss of a defined wall layer close to the plasma membrane. 26809064 3 73 from data 387:390 arg1 phenotypes 405:414 cell wall phenotypes 395:414 cell wall phenotypes of goa1∆ (strain GOA31) 395:438 Herein, we present data on cell wall phenotypes of goa1∆ (strain GOA31). 26809064 7 74 theme linkages 864:871 arg1 reduction 821:829 A reduction 819:829 A reduction of β-mannosyl but not α-mannosyl linkages 819:871 A reduction of β-mannosyl but not α-mannosyl linkages was noted in GOA31 cells. 26792378 14 0 theme superovulated 2227:2239 arg1 samples 2241:2247 superovulated samples 2227:2247 superovulated samples 2227:2247 The cytoplasm of normal ciliated cells cells displayed a binding pattern similar to normal NCs except for the absence of higly mannosilated N-glycans in the folds, which appeared in superovulated samples. 26792378 10 1 theme LFucα1,2 1500:1507 arg1 Gal 1480:1482 Gal 1480:1482 Gal 1480:1482 In SE, the luminal surface lacked Gal and GalNAcα1, 3(LFucα1,2)Galβ1,3/4GlcNAcβ1, whereas it was enriched with Fuc in the folds and with α2-3sialo-mucins both in crypts and in folds. 26792378 10 1 theme LFucα1,2 1500:1507 arg1 Galβ1,3/4GlcNAcβ1 1509:1525 3(LFucα1,2)Galβ1,3/4GlcNAcβ1 1498:1525 3(LFucα1,2)Galβ1,3/4GlcNAcβ1 1498:1525 In SE, the luminal surface lacked Gal and GalNAcα1, 3(LFucα1,2)Galβ1,3/4GlcNAcβ1, whereas it was enriched with Fuc in the folds and with α2-3sialo-mucins both in crypts and in folds. 26792378 5 2 from normal 681:686 arg1 cells 664:668 Nonciliated cells 652:668 Nonciliated cells (NCs) 652:674 Nonciliated cells (NCs) from normal, showed apical blebs revealing apocrine secretory activity, which was missing in SE. 26792378 5 2 from normal 681:686 arg1 NCs 671:673 NCs 671:673 NCs 671:673 Nonciliated cells (NCs) from normal, showed apical blebs revealing apocrine secretory activity, which was missing in SE. 26792378 14 3 theme normal 2129:2134 arg1 NCs 2136:2138 normal NCs 2129:2138 normal NCs 2129:2138 The cytoplasm of normal ciliated cells cells displayed a binding pattern similar to normal NCs except for the absence of higly mannosilated N-glycans in the folds, which appeared in superovulated samples. 26792378 11 4 theme apical 1633:1638 arg1 surface 1640:1646 The apical surface 1629:1646 The apical surface 1629:1646 The apical surface showed additional O- and N-linked sialoglycans in NCs and αGal in the cilia, which expressed α2-6-linked sialic acid only in the folds. 26792378 2 5 from events 341:346 arg1 SE 375:376 SE 375:376 SE 375:376 Isthmus morphology and glycoprotein production are controlled by sex steroids, which could be responsible for alterations of some reproductive events in the superovulated ewes (SE). 26792378 2 5 from events 341:346 arg1 ewes 369:372 the superovulated ewes 351:372 the superovulated ewes (SE) 351:377 Isthmus morphology and glycoprotein production are controlled by sex steroids, which could be responsible for alterations of some reproductive events in the superovulated ewes (SE). 26792378 3 6 theme oviductal 399:407 arg1 epithelium 417:426 the oviductal isthmus epithelium 395:426 the oviductal isthmus epithelium 395:426 In this study, the oviductal isthmus epithelium was evaluated in normal and in SE using morphologic and lectin histochemical analysis. 26792378 14 7 theme similar 2118:2124 arg1 pattern 2110:2116 a binding pattern 2100:2116 a binding pattern similar to normal NCs 2100:2138 The cytoplasm of normal ciliated cells cells displayed a binding pattern similar to normal NCs except for the absence of higly mannosilated N-glycans in the folds, which appeared in superovulated samples. 26792378 0 8 theme Glycan 0:5 arg1 profile 7:13 Glycan profile 0:13 Glycan profile of oviductal isthmus epithelium in normal and superovulated ewes. 0:79 Glycan profile of oviductal isthmus epithelium in normal and superovulated ewes. 26792378 11 9 link N-linked 1673:1680 arg1 sialoglycans 1682:1693 additional O- and N-linked sialoglycans 1655:1693 additional O- and N-linked sialoglycans 1655:1693 The apical surface showed additional O- and N-linked sialoglycans in NCs and αGal in the cilia, which expressed α2-6-linked sialic acid only in the folds. 26792378 6 10 theme superovulated 1005:1017 arg1 ones 1019:1022 superovulated ones 1005:1022 superovulated ones 1005:1022 The quantitative analysis of lectin staining revealed higher Con A, DBA, and PNA reactivity but lower affinity to KOH-sialidase- (Ks)WGA, GSA II, LTA, UEA I, SBA, GSA I-B4, RCA120, KsPNA, MAL II, SNA in control isthmi compared with superovulated ones. 26792378 14 11 theme binding 2102:2108 arg1 pattern 2110:2116 a binding pattern 2100:2116 a binding pattern similar to normal NCs 2100:2138 The cytoplasm of normal ciliated cells cells displayed a binding pattern similar to normal NCs except for the absence of higly mannosilated N-glycans in the folds, which appeared in superovulated samples. 26792378 2 12 from ewes 369:372 arg1 alterations 308:318 alterations 308:318 alterations of some reproductive events in the superovulated ewes (SE) 308:377 Isthmus morphology and glycoprotein production are controlled by sex steroids, which could be responsible for alterations of some reproductive events in the superovulated ewes (SE). 26792378 9 13 contain contained 1402:1410 arg2 acids 1439:1443 Gal and α2-3-linked sialic acids 1412:1443 Gal and α2-3-linked sialic acids 1412:1443 Moreover, NCs microvilli contained Gal and α2-3-linked sialic acids. 26792378 9 13 contain contained 1402:1410 arg1 microvilli 1391:1400 NCs microvilli 1387:1400 NCs microvilli 1387:1400 Moreover, NCs microvilli contained Gal and α2-3-linked sialic acids. 26792378 15 14 theme superovulation 2363:2376 arg1 treatment 2378:2386 the superovulation treatment 2359:2386 the superovulation treatment 2359:2386 This study demonstrates glycan zone-specific distribution along the isthmus epithelium that is influenced by the superovulation treatment. 26792378 13 15 theme superovulation 1907:1920 arg1 treatment 1922:1930 superovulation treatment 1907:1930 superovulation treatment 1907:1930 After superovulation treatment, NCs expressed cytoplasmic terminal Fuc, βGalNAc, lactosamine, α2-3-, and α2-6-linked sialic acids in the folds. 26792378 8 16 theme mannosilated 1251:1262 arg1 N-glycans 1264:1272 highly mannosilated N-glycans 1244:1272 highly mannosilated N-glycans terminating with lactosamine as well as O-glycans ending with N-acetylglucosamine (GlcNAc) and GalNAc 1244:1374 In normal isthmi, the luminal surface of NCs and ciliated cells expressed Fuc, highly mannosilated N-glycans terminating with lactosamine as well as O-glycans ending with N-acetylglucosamine (GlcNAc) and GalNAc. 26792378 8 16 theme mannosilated 1251:1262 arg1 Fuc 1239:1241 Fuc 1239:1241 Fuc 1239:1241 In normal isthmi, the luminal surface of NCs and ciliated cells expressed Fuc, highly mannosilated N-glycans terminating with lactosamine as well as O-glycans ending with N-acetylglucosamine (GlcNAc) and GalNAc. 26792378 12 17 theme mannosilated 1827:1838 arg1 N-glycans 1840:1848 highly mannosilated N-glycans 1820:1848 highly mannosilated N-glycans 1820:1848 The cytoplasm of control NCs showed highly mannosilated N-glycans throughout the epithelium and GlcNAc in the folds. 26792378 2 18 gly glycoprotein 221:232 arg1 glycoprotein 221:232 glycoprotein production 221:243 glycoprotein production 221:243 Isthmus morphology and glycoprotein production are controlled by sex steroids, which could be responsible for alterations of some reproductive events in the superovulated ewes (SE). 26792378 5 19 theme Nonciliated 652:662 arg1 cells 664:668 Nonciliated cells 652:668 Nonciliated cells (NCs) 652:674 Nonciliated cells (NCs) from normal, showed apical blebs revealing apocrine secretory activity, which was missing in SE. 26792378 5 19 theme Nonciliated 652:662 arg1 NCs 671:673 NCs 671:673 NCs 671:673 Nonciliated cells (NCs) from normal, showed apical blebs revealing apocrine secretory activity, which was missing in SE. 26792378 6 20 theme lower 869:873 arg1 affinity 875:882 lower affinity 869:882 lower affinity to KOH-sialidase- (Ks)WGA, GSA II, LTA, UEA I, SBA, GSA I-B4, RCA120, KsPNA, MAL II, SNA in control isthmi 869:989 The quantitative analysis of lectin staining revealed higher Con A, DBA, and PNA reactivity but lower affinity to KOH-sialidase- (Ks)WGA, GSA II, LTA, UEA I, SBA, GSA I-B4, RCA120, KsPNA, MAL II, SNA in control isthmi compared with superovulated ones. 26792378 10 21 dep the 1564:1566 arg1 folds 1568:1572 folds 1568:1572 folds 1568:1572 In SE, the luminal surface lacked Gal and GalNAcα1, 3(LFucα1,2)Galβ1,3/4GlcNAcβ1, whereas it was enriched with Fuc in the folds and with α2-3sialo-mucins both in crypts and in folds. 26792378 9 22 theme NCs 1387:1389 arg1 microvilli 1391:1400 NCs microvilli 1387:1400 NCs microvilli 1387:1400 Moreover, NCs microvilli contained Gal and α2-3-linked sialic acids. 26792378 11 23 theme sialic 1753:1758 arg1 acid 1760:1763 α2-6-linked sialic acid 1741:1763 α2-6-linked sialic acid 1741:1763 The apical surface showed additional O- and N-linked sialoglycans in NCs and αGal in the cilia, which expressed α2-6-linked sialic acid only in the folds. 26792378 11 24 dep the 1773:1775 arg1 folds 1777:1781 folds 1777:1781 folds 1777:1781 The apical surface showed additional O- and N-linked sialoglycans in NCs and αGal in the cilia, which expressed α2-6-linked sialic acid only in the folds. 26792378 6 25 theme UEA 924:926 arg1 KOH-sialidase- 887:900 KOH-sialidase- 887:900 KOH-sialidase- 887:900 The quantitative analysis of lectin staining revealed higher Con A, DBA, and PNA reactivity but lower affinity to KOH-sialidase- (Ks)WGA, GSA II, LTA, UEA I, SBA, GSA I-B4, RCA120, KsPNA, MAL II, SNA in control isthmi compared with superovulated ones. 26792378 6 25 theme UEA 924:926 arg1 I 928:928 UEA I 924:928 UEA I 924:928 The quantitative analysis of lectin staining revealed higher Con A, DBA, and PNA reactivity but lower affinity to KOH-sialidase- (Ks)WGA, GSA II, LTA, UEA I, SBA, GSA I-B4, RCA120, KsPNA, MAL II, SNA in control isthmi compared with superovulated ones. 26792378 16 26 theme superovulated 2510:2522 arg1 sheep 2524:2528 the superovulated sheep 2506:2528 the superovulated sheep 2506:2528 Whether an alteration in the glycan distribution is implicated in the low-rate fertilization after natural mating of the superovulated sheep remains to be addressed. 26792378 12 27 theme control 1801:1807 arg1 NCs 1809:1811 control NCs 1801:1811 control NCs 1801:1811 The cytoplasm of control NCs showed highly mannosilated N-glycans throughout the epithelium and GlcNAc in the folds. 26792378 14 28 theme cells 2084:2088 arg1 cytoplasm 2049:2057 The cytoplasm 2045:2057 The cytoplasm of normal ciliated cells cells 2045:2088 The cytoplasm of normal ciliated cells cells displayed a binding pattern similar to normal NCs except for the absence of higly mannosilated N-glycans in the folds, which appeared in superovulated samples. 26792378 5 29 theme apocrine 719:726 arg1 activity 738:745 apocrine secretory activity 719:745 apocrine secretory activity 719:745 Nonciliated cells (NCs) from normal, showed apical blebs revealing apocrine secretory activity, which was missing in SE. 26792378 13 30 theme α2-6-linked 2006:2016 arg1 acids 2025:2029 α2-6-linked sialic acids 2006:2029 α2-6-linked sialic acids 2006:2029 After superovulation treatment, NCs expressed cytoplasmic terminal Fuc, βGalNAc, lactosamine, α2-3-, and α2-6-linked sialic acids in the folds. 26792378 14 31 dep the 2198:2200 arg1 folds 2202:2206 folds 2202:2206 folds 2202:2206 The cytoplasm of normal ciliated cells cells displayed a binding pattern similar to normal NCs except for the absence of higly mannosilated N-glycans in the folds, which appeared in superovulated samples. 26792378 2 32 theme sex 263:265 arg1 steroids 267:274 sex steroids 263:274 sex steroids 263:274 Isthmus morphology and glycoprotein production are controlled by sex steroids, which could be responsible for alterations of some reproductive events in the superovulated ewes (SE). 26792378 7 33 theme terminal 1053:1060 arg1 Fuc 1070:1072 Fuc 1070:1072 Fuc 1070:1072 The NCs apical blebs showed terminal fucose (Fuc), N-acetylgalactosamine (GalNAc), galactose (Gal), lactosamine, and O- and N-sialoglycans. 26792378 7 33 theme terminal 1053:1060 arg1 fucose 1062:1067 terminal fucose 1053:1067 terminal fucose (Fuc) 1053:1073 The NCs apical blebs showed terminal fucose (Fuc), N-acetylgalactosamine (GalNAc), galactose (Gal), lactosamine, and O- and N-sialoglycans. 26792378 15 34 theme glycan 2274:2279 arg1 distribution 2295:2306 glycan zone-specific distribution 2274:2306 glycan zone-specific distribution along the isthmus epithelium that is influenced by the superovulation treatment 2274:2386 This study demonstrates glycan zone-specific distribution along the isthmus epithelium that is influenced by the superovulation treatment. 26792378 1 35 theme sperm-isthmus 128:140 arg1 interaction 142:152 sperm-isthmus interaction 128:152 sperm-isthmus interaction 128:152 Glycans of oviductal isthmus are implicated in sperm-isthmus interaction, sperm storage, survival, and capacitation. 26792378 8 36 theme normal 1168:1173 arg1 isthmi 1175:1180 normal isthmi 1168:1180 normal isthmi 1168:1180 In normal isthmi, the luminal surface of NCs and ciliated cells expressed Fuc, highly mannosilated N-glycans terminating with lactosamine as well as O-glycans ending with N-acetylglucosamine (GlcNAc) and GalNAc. 26792378 10 37 theme luminal 1457:1463 arg1 surface 1465:1471 the luminal surface 1453:1471 the luminal surface 1453:1471 In SE, the luminal surface lacked Gal and GalNAcα1, 3(LFucα1,2)Galβ1,3/4GlcNAcβ1, whereas it was enriched with Fuc in the folds and with α2-3sialo-mucins both in crypts and in folds. 26792378 12 38 from GlcNAc 1880:1885 arg1 the 1890:1892 the 1890:1892 the 1890:1892 The cytoplasm of control NCs showed highly mannosilated N-glycans throughout the epithelium and GlcNAc in the folds. 26792378 10 39 from α2-3sialo-mucins 1583:1598 arg1 crypts 1608:1613 crypts 1608:1613 crypts 1608:1613 In SE, the luminal surface lacked Gal and GalNAcα1, 3(LFucα1,2)Galβ1,3/4GlcNAcβ1, whereas it was enriched with Fuc in the folds and with α2-3sialo-mucins both in crypts and in folds. 26792378 10 39 from α2-3sialo-mucins 1583:1598 arg1 folds 1622:1626 folds 1622:1626 folds 1622:1626 In SE, the luminal surface lacked Gal and GalNAcα1, 3(LFucα1,2)Galβ1,3/4GlcNAcβ1, whereas it was enriched with Fuc in the folds and with α2-3sialo-mucins both in crypts and in folds. 26792378 11 40 theme O- 1666:1667 arg1 sialoglycans 1682:1693 additional O- and N-linked sialoglycans 1655:1693 additional O- and N-linked sialoglycans 1655:1693 The apical surface showed additional O- and N-linked sialoglycans in NCs and αGal in the cilia, which expressed α2-6-linked sialic acid only in the folds. 26792378 7 41 theme NCs 1029:1031 arg1 blebs 1040:1044 The NCs apical blebs 1025:1044 The NCs apical blebs 1025:1044 The NCs apical blebs showed terminal fucose (Fuc), N-acetylgalactosamine (GalNAc), galactose (Gal), lactosamine, and O- and N-sialoglycans. 26792378 12 42 from epithelium 1865:1874 arg1 the 1890:1892 the 1890:1892 the 1890:1892 The cytoplasm of control NCs showed highly mannosilated N-glycans throughout the epithelium and GlcNAc in the folds. 26792378 11 43 link α2-6-linked 1741:1751 arg1 acid 1760:1763 α2-6-linked sialic acid 1741:1763 α2-6-linked sialic acid 1741:1763 The apical surface showed additional O- and N-linked sialoglycans in NCs and αGal in the cilia, which expressed α2-6-linked sialic acid only in the folds. 26792378 4 44 theme normal 533:538 arg1 isthmi 540:545 normal isthmi 533:545 normal isthmi 533:545 The epithelium of normal isthmi was significantly taller in folds than in crypts, whereas it significantly decreased in the folds of SE. 26792378 8 45 theme luminal 1187:1193 arg1 surface 1195:1201 the luminal surface 1183:1201 the luminal surface of NCs and ciliated cells 1183:1227 In normal isthmi, the luminal surface of NCs and ciliated cells expressed Fuc, highly mannosilated N-glycans terminating with lactosamine as well as O-glycans ending with N-acetylglucosamine (GlcNAc) and GalNAc. 26792378 6 46 theme Con 834:836 arg1 A 838:838 higher Con A 827:838 higher Con A 827:838 The quantitative analysis of lectin staining revealed higher Con A, DBA, and PNA reactivity but lower affinity to KOH-sialidase- (Ks)WGA, GSA II, LTA, UEA I, SBA, GSA I-B4, RCA120, KsPNA, MAL II, SNA in control isthmi compared with superovulated ones. 26792378 1 47 theme isthmus 102:108 arg1 Glycans 81:87 Glycans 81:87 Glycans of oviductal isthmus 81:108 Glycans of oviductal isthmus are implicated in sperm-isthmus interaction, sperm storage, survival, and capacitation. 26792378 14 48 theme ciliated 2069:2076 arg1 cells 2084:2088 normal ciliated cells cells 2062:2088 normal ciliated cells cells 2062:2088 The cytoplasm of normal ciliated cells cells displayed a binding pattern similar to normal NCs except for the absence of higly mannosilated N-glycans in the folds, which appeared in superovulated samples. 26792378 0 49 theme isthmus 28:34 arg1 epithelium 36:45 oviductal isthmus epithelium 18:45 oviductal isthmus epithelium 18:45 Glycan profile of oviductal isthmus epithelium in normal and superovulated ewes. 26792378 9 50 theme Gal 1412:1414 arg1 acids 1439:1443 Gal and α2-3-linked sialic acids 1412:1443 Gal and α2-3-linked sialic acids 1412:1443 Moreover, NCs microvilli contained Gal and α2-3-linked sialic acids. 26792378 16 51 theme sheep 2524:2528 arg1 mating 2496:2501 natural mating 2488:2501 natural mating of the superovulated sheep 2488:2528 Whether an alteration in the glycan distribution is implicated in the low-rate fertilization after natural mating of the superovulated sheep remains to be addressed. 26792378 14 52 theme N-glycans 2185:2193 arg1 absence 2155:2161 the absence 2151:2161 the absence of higly mannosilated N-glycans in the folds, which appeared in superovulated samples 2151:2247 The cytoplasm of normal ciliated cells cells displayed a binding pattern similar to normal NCs except for the absence of higly mannosilated N-glycans in the folds, which appeared in superovulated samples. 26792378 6 53 theme lectin 802:807 arg1 staining 809:816 lectin staining 802:816 lectin staining 802:816 The quantitative analysis of lectin staining revealed higher Con A, DBA, and PNA reactivity but lower affinity to KOH-sialidase- (Ks)WGA, GSA II, LTA, UEA I, SBA, GSA I-B4, RCA120, KsPNA, MAL II, SNA in control isthmi compared with superovulated ones. 26792378 9 54 theme α2-3-linked 1420:1430 arg1 acids 1439:1443 Gal and α2-3-linked sialic acids 1412:1443 Gal and α2-3-linked sialic acids 1412:1443 Moreover, NCs microvilli contained Gal and α2-3-linked sialic acids. 26792378 16 55 theme glycan 2418:2423 arg1 distribution 2425:2436 the glycan distribution 2414:2436 the glycan distribution 2414:2436 Whether an alteration in the glycan distribution is implicated in the low-rate fertilization after natural mating of the superovulated sheep remains to be addressed. 26792378 2 56 theme Isthmus 198:204 arg1 morphology 206:215 Isthmus morphology 198:215 Isthmus morphology 198:215 Isthmus morphology and glycoprotein production are controlled by sex steroids, which could be responsible for alterations of some reproductive events in the superovulated ewes (SE). 26792378 8 57 theme cells 1223:1227 arg1 surface 1195:1201 the luminal surface 1183:1201 the luminal surface of NCs and ciliated cells 1183:1227 In normal isthmi, the luminal surface of NCs and ciliated cells expressed Fuc, highly mannosilated N-glycans terminating with lactosamine as well as O-glycans ending with N-acetylglucosamine (GlcNAc) and GalNAc. 26792378 2 58 theme reproductive 328:339 arg1 events 341:346 some reproductive events 323:346 some reproductive events in the superovulated ewes (SE) 323:377 Isthmus morphology and glycoprotein production are controlled by sex steroids, which could be responsible for alterations of some reproductive events in the superovulated ewes (SE). 26792378 3 59 theme histochemical 491:503 arg1 analysis 505:512 morphologic and lectin histochemical analysis 468:512 morphologic and lectin histochemical analysis 468:512 In this study, the oviductal isthmus epithelium was evaluated in normal and in SE using morphologic and lectin histochemical analysis. 26792378 13 60 theme cytoplasmic 1947:1957 arg1 Fuc 1968:1970 cytoplasmic terminal Fuc 1947:1970 cytoplasmic terminal Fuc 1947:1970 After superovulation treatment, NCs expressed cytoplasmic terminal Fuc, βGalNAc, lactosamine, α2-3-, and α2-6-linked sialic acids in the folds. 26792378 4 61 dep the 635:637 arg1 folds 639:643 folds 639:643 folds 639:643 The epithelium of normal isthmi was significantly taller in folds than in crypts, whereas it significantly decreased in the folds of SE. 26792378 2 62 theme superovulated 355:367 arg1 SE 375:376 SE 375:376 SE 375:376 Isthmus morphology and glycoprotein production are controlled by sex steroids, which could be responsible for alterations of some reproductive events in the superovulated ewes (SE). 26792378 2 62 theme superovulated 355:367 arg1 ewes 369:372 the superovulated ewes 351:372 the superovulated ewes (SE) 351:377 Isthmus morphology and glycoprotein production are controlled by sex steroids, which could be responsible for alterations of some reproductive events in the superovulated ewes (SE). 26792378 6 63 theme PNA 850:852 arg1 reactivity 854:863 PNA reactivity 850:863 PNA reactivity 850:863 The quantitative analysis of lectin staining revealed higher Con A, DBA, and PNA reactivity but lower affinity to KOH-sialidase- (Ks)WGA, GSA II, LTA, UEA I, SBA, GSA I-B4, RCA120, KsPNA, MAL II, SNA in control isthmi compared with superovulated ones. 26792378 16 64 theme low-rate 2459:2466 arg1 fertilization 2468:2480 the low-rate fertilization 2455:2480 the low-rate fertilization 2455:2480 Whether an alteration in the glycan distribution is implicated in the low-rate fertilization after natural mating of the superovulated sheep remains to be addressed. 26792378 15 65 theme isthmus 2318:2324 arg1 epithelium 2326:2335 the isthmus epithelium 2314:2335 the isthmus epithelium that is influenced by the superovulation treatment 2314:2386 This study demonstrates glycan zone-specific distribution along the isthmus epithelium that is influenced by the superovulation treatment. 26792378 13 66 theme sialic 2018:2023 arg1 acids 2025:2029 α2-6-linked sialic acids 2006:2029 α2-6-linked sialic acids 2006:2029 After superovulation treatment, NCs expressed cytoplasmic terminal Fuc, βGalNAc, lactosamine, α2-3-, and α2-6-linked sialic acids in the folds. 26792378 16 67 from alteration 2400:2409 arg1 distribution 2425:2436 the glycan distribution 2414:2436 the glycan distribution 2414:2436 Whether an alteration in the glycan distribution is implicated in the low-rate fertilization after natural mating of the superovulated sheep remains to be addressed. 26792378 2 68 theme events 341:346 arg1 alterations 308:318 alterations 308:318 alterations of some reproductive events in the superovulated ewes (SE) 308:377 Isthmus morphology and glycoprotein production are controlled by sex steroids, which could be responsible for alterations of some reproductive events in the superovulated ewes (SE). 26792378 9 69 link α2-3-linked 1420:1430 arg1 acids 1439:1443 Gal and α2-3-linked sialic acids 1412:1443 Gal and α2-3-linked sialic acids 1412:1443 Moreover, NCs microvilli contained Gal and α2-3-linked sialic acids. 26792378 6 70 dep KOH-sialidase- 887:900 arg1 WGA 906:908 WGA 906:908 WGA 906:908 The quantitative analysis of lectin staining revealed higher Con A, DBA, and PNA reactivity but lower affinity to KOH-sialidase- (Ks)WGA, GSA II, LTA, UEA I, SBA, GSA I-B4, RCA120, KsPNA, MAL II, SNA in control isthmi compared with superovulated ones. 26792378 2 71 theme glycoprotein 221:232 arg1 production 234:243 glycoprotein production 221:243 glycoprotein production 221:243 Isthmus morphology and glycoprotein production are controlled by sex steroids, which could be responsible for alterations of some reproductive events in the superovulated ewes (SE). 26792378 14 72 from N-glycans 2185:2193 arg1 the 2198:2200 the 2198:2200 the 2198:2200 The cytoplasm of normal ciliated cells cells displayed a binding pattern similar to normal NCs except for the absence of higly mannosilated N-glycans in the folds, which appeared in superovulated samples. 26792378 11 73 theme α2-6-linked 1741:1751 arg1 acid 1760:1763 α2-6-linked sialic acid 1741:1763 α2-6-linked sialic acid 1741:1763 The apical surface showed additional O- and N-linked sialoglycans in NCs and αGal in the cilia, which expressed α2-6-linked sialic acid only in the folds. 26792378 14 74 theme cells 2078:2082 arg1 cells 2084:2088 normal ciliated cells cells 2062:2088 normal ciliated cells cells 2062:2088 The cytoplasm of normal ciliated cells cells displayed a binding pattern similar to normal NCs except for the absence of higly mannosilated N-glycans in the folds, which appeared in superovulated samples. 26792378 0 75 theme superovulated 61:73 arg1 ewes 75:78 normal and superovulated ewes 50:78 normal and superovulated ewes 50:78 Glycan profile of oviductal isthmus epithelium in normal and superovulated ewes. 26792378 14 76 from absence 2155:2161 arg1 the 2198:2200 the 2198:2200 the 2198:2200 The cytoplasm of normal ciliated cells cells displayed a binding pattern similar to normal NCs except for the absence of higly mannosilated N-glycans in the folds, which appeared in superovulated samples. 26792378 14 77 theme normal 2062:2067 arg1 cells 2084:2088 normal ciliated cells cells 2062:2088 normal ciliated cells cells 2062:2088 The cytoplasm of normal ciliated cells cells displayed a binding pattern similar to normal NCs except for the absence of higly mannosilated N-glycans in the folds, which appeared in superovulated samples. 26792378 5 78 theme secretory 728:736 arg1 activity 738:745 apocrine secretory activity 719:745 apocrine secretory activity 719:745 Nonciliated cells (NCs) from normal, showed apical blebs revealing apocrine secretory activity, which was missing in SE. 26792378 1 79 theme sperm 155:159 arg1 storage 161:167 sperm storage 155:167 sperm storage 155:167 Glycans of oviductal isthmus are implicated in sperm-isthmus interaction, sperm storage, survival, and capacitation. 26792378 0 80 from profile 7:13 arg1 ewes 75:78 normal and superovulated ewes 50:78 normal and superovulated ewes 50:78 Glycan profile of oviductal isthmus epithelium in normal and superovulated ewes. 26792378 12 81 theme NCs 1809:1811 arg1 cytoplasm 1788:1796 The cytoplasm 1784:1796 The cytoplasm of control NCs 1784:1811 The cytoplasm of control NCs showed highly mannosilated N-glycans throughout the epithelium and GlcNAc in the folds. 26792378 3 82 dep in 456:457 arg1 SE 459:460 SE 459:460 SE 459:460 In this study, the oviductal isthmus epithelium was evaluated in normal and in SE using morphologic and lectin histochemical analysis. 26792378 2 83 from alterations 308:318 arg1 SE 375:376 SE 375:376 SE 375:376 Isthmus morphology and glycoprotein production are controlled by sex steroids, which could be responsible for alterations of some reproductive events in the superovulated ewes (SE). 26792378 2 83 from alterations 308:318 arg1 ewes 369:372 the superovulated ewes 351:372 the superovulated ewes (SE) 351:377 Isthmus morphology and glycoprotein production are controlled by sex steroids, which could be responsible for alterations of some reproductive events in the superovulated ewes (SE). 26792378 5 84 theme apical 696:701 arg1 blebs 703:707 apical blebs 696:707 apical blebs 696:707 Nonciliated cells (NCs) from normal, showed apical blebs revealing apocrine secretory activity, which was missing in SE. 26792378 15 85 theme zone-specific 2281:2293 arg1 distribution 2295:2306 glycan zone-specific distribution 2274:2306 glycan zone-specific distribution along the isthmus epithelium that is influenced by the superovulation treatment 2274:2386 This study demonstrates glycan zone-specific distribution along the isthmus epithelium that is influenced by the superovulation treatment. 26792378 16 86 theme natural 2488:2494 arg1 mating 2496:2501 natural mating 2488:2501 natural mating of the superovulated sheep 2488:2528 Whether an alteration in the glycan distribution is implicated in the low-rate fertilization after natural mating of the superovulated sheep remains to be addressed. 26792378 14 87 from the 2198:2200 arg1 absence 2155:2161 the absence 2151:2161 the absence of higly mannosilated N-glycans in the folds, which appeared in superovulated samples 2151:2247 The cytoplasm of normal ciliated cells cells displayed a binding pattern similar to normal NCs except for the absence of higly mannosilated N-glycans in the folds, which appeared in superovulated samples. 26792378 13 88 dep the 2034:2036 arg1 folds 2038:2042 folds 2038:2042 folds 2038:2042 After superovulation treatment, NCs expressed cytoplasmic terminal Fuc, βGalNAc, lactosamine, α2-3-, and α2-6-linked sialic acids in the folds. 26792378 7 89 theme apical 1033:1038 arg1 blebs 1040:1044 The NCs apical blebs 1025:1044 The NCs apical blebs 1025:1044 The NCs apical blebs showed terminal fucose (Fuc), N-acetylgalactosamine (GalNAc), galactose (Gal), lactosamine, and O- and N-sialoglycans. 26792378 4 90 theme isthmi 540:545 arg1 epithelium 519:528 The epithelium 515:528 The epithelium of normal isthmi 515:545 The epithelium of normal isthmi was significantly taller in folds than in crypts, whereas it significantly decreased in the folds of SE. 26792378 4 90 theme isthmi 540:545 arg1 taller 565:570 taller 565:570 taller 565:570 The epithelium of normal isthmi was significantly taller in folds than in crypts, whereas it significantly decreased in the folds of SE. 26792378 3 91 theme isthmus 409:415 arg1 epithelium 417:426 the oviductal isthmus epithelium 395:426 the oviductal isthmus epithelium 395:426 In this study, the oviductal isthmus epithelium was evaluated in normal and in SE using morphologic and lectin histochemical analysis. 26792378 0 92 theme oviductal 18:26 arg1 epithelium 36:45 oviductal isthmus epithelium 18:45 oviductal isthmus epithelium 18:45 Glycan profile of oviductal isthmus epithelium in normal and superovulated ewes. 26792378 1 93 theme oviductal 92:100 arg1 isthmus 102:108 oviductal isthmus 92:108 oviductal isthmus 92:108 Glycans of oviductal isthmus are implicated in sperm-isthmus interaction, sperm storage, survival, and capacitation. 26792378 6 94 theme GSA 936:938 arg1 KOH-sialidase- 887:900 KOH-sialidase- 887:900 KOH-sialidase- 887:900 The quantitative analysis of lectin staining revealed higher Con A, DBA, and PNA reactivity but lower affinity to KOH-sialidase- (Ks)WGA, GSA II, LTA, UEA I, SBA, GSA I-B4, RCA120, KsPNA, MAL II, SNA in control isthmi compared with superovulated ones. 26792378 6 94 theme GSA 936:938 arg1 I-B4 940:943 GSA I-B4 936:943 GSA I-B4 936:943 The quantitative analysis of lectin staining revealed higher Con A, DBA, and PNA reactivity but lower affinity to KOH-sialidase- (Ks)WGA, GSA II, LTA, UEA I, SBA, GSA I-B4, RCA120, KsPNA, MAL II, SNA in control isthmi compared with superovulated ones. 26792378 0 95 theme epithelium 36:45 arg1 profile 7:13 Glycan profile 0:13 Glycan profile of oviductal isthmus epithelium in normal and superovulated ewes. 0:79 Glycan profile of oviductal isthmus epithelium in normal and superovulated ewes. 26792378 6 96 theme higher 827:832 arg1 A 838:838 higher Con A 827:838 higher Con A 827:838 The quantitative analysis of lectin staining revealed higher Con A, DBA, and PNA reactivity but lower affinity to KOH-sialidase- (Ks)WGA, GSA II, LTA, UEA I, SBA, GSA I-B4, RCA120, KsPNA, MAL II, SNA in control isthmi compared with superovulated ones. 26792378 11 97 theme N-linked 1673:1680 arg1 sialoglycans 1682:1693 additional O- and N-linked sialoglycans 1655:1693 additional O- and N-linked sialoglycans 1655:1693 The apical surface showed additional O- and N-linked sialoglycans in NCs and αGal in the cilia, which expressed α2-6-linked sialic acid only in the folds. 26792378 13 98 link α2-6-linked 2006:2016 arg1 acids 2025:2029 α2-6-linked sialic acids 2006:2029 α2-6-linked sialic acids 2006:2029 After superovulation treatment, NCs expressed cytoplasmic terminal Fuc, βGalNAc, lactosamine, α2-3-, and α2-6-linked sialic acids in the folds. 26792378 6 99 from SNA 969:971 arg1 isthmi 984:989 control isthmi 976:989 control isthmi 976:989 The quantitative analysis of lectin staining revealed higher Con A, DBA, and PNA reactivity but lower affinity to KOH-sialidase- (Ks)WGA, GSA II, LTA, UEA I, SBA, GSA I-B4, RCA120, KsPNA, MAL II, SNA in control isthmi compared with superovulated ones. 26792378 0 100 theme normal 50:55 arg1 ewes 75:78 normal and superovulated ewes 50:78 normal and superovulated ewes 50:78 Glycan profile of oviductal isthmus epithelium in normal and superovulated ewes. 26792378 6 101 theme staining 809:816 arg1 analysis 790:797 The quantitative analysis 773:797 The quantitative analysis of lectin staining 773:816 The quantitative analysis of lectin staining revealed higher Con A, DBA, and PNA reactivity but lower affinity to KOH-sialidase- (Ks)WGA, GSA II, LTA, UEA I, SBA, GSA I-B4, RCA120, KsPNA, MAL II, SNA in control isthmi compared with superovulated ones. 26792378 12 102 dep epithelium 1865:1874 arg1 the 1861:1863 the 1861:1863 the 1861:1863 The cytoplasm of control NCs showed highly mannosilated N-glycans throughout the epithelium and GlcNAc in the folds. 26792378 6 103 theme control 976:982 arg1 isthmi 984:989 control isthmi 976:989 control isthmi 976:989 The quantitative analysis of lectin staining revealed higher Con A, DBA, and PNA reactivity but lower affinity to KOH-sialidase- (Ks)WGA, GSA II, LTA, UEA I, SBA, GSA I-B4, RCA120, KsPNA, MAL II, SNA in control isthmi compared with superovulated ones. 26792378 8 104 theme NCs 1206:1208 arg1 surface 1195:1201 the luminal surface 1183:1201 the luminal surface of NCs and ciliated cells 1183:1227 In normal isthmi, the luminal surface of NCs and ciliated cells expressed Fuc, highly mannosilated N-glycans terminating with lactosamine as well as O-glycans ending with N-acetylglucosamine (GlcNAc) and GalNAc. 26792378 14 105 theme mannosilated 2172:2183 arg1 N-glycans 2185:2193 higly mannosilated N-glycans 2166:2193 higly mannosilated N-glycans in the folds, which appeared in superovulated samples 2166:2247 The cytoplasm of normal ciliated cells cells displayed a binding pattern similar to normal NCs except for the absence of higly mannosilated N-glycans in the folds, which appeared in superovulated samples. 26792378 3 106 theme morphologic 468:478 arg1 analysis 505:512 morphologic and lectin histochemical analysis 468:512 morphologic and lectin histochemical analysis 468:512 In this study, the oviductal isthmus epithelium was evaluated in normal and in SE using morphologic and lectin histochemical analysis. 26792378 9 107 theme sialic 1432:1437 arg1 acids 1439:1443 Gal and α2-3-linked sialic acids 1412:1443 Gal and α2-3-linked sialic acids 1412:1443 Moreover, NCs microvilli contained Gal and α2-3-linked sialic acids. 26792378 8 108 theme ciliated 1214:1221 arg1 cells 1223:1227 ciliated cells 1214:1227 ciliated cells 1214:1227 In normal isthmi, the luminal surface of NCs and ciliated cells expressed Fuc, highly mannosilated N-glycans terminating with lactosamine as well as O-glycans ending with N-acetylglucosamine (GlcNAc) and GalNAc. 26792378 6 109 theme quantitative 777:788 arg1 analysis 790:797 The quantitative analysis 773:797 The quantitative analysis of lectin staining 773:816 The quantitative analysis of lectin staining revealed higher Con A, DBA, and PNA reactivity but lower affinity to KOH-sialidase- (Ks)WGA, GSA II, LTA, UEA I, SBA, GSA I-B4, RCA120, KsPNA, MAL II, SNA in control isthmi compared with superovulated ones. 26792378 12 110 dep the 1890:1892 arg1 folds 1894:1898 folds 1894:1898 folds 1894:1898 The cytoplasm of control NCs showed highly mannosilated N-glycans throughout the epithelium and GlcNAc in the folds. 26792378 11 111 theme additional 1655:1664 arg1 sialoglycans 1682:1693 additional O- and N-linked sialoglycans 1655:1693 additional O- and N-linked sialoglycans 1655:1693 The apical surface showed additional O- and N-linked sialoglycans in NCs and αGal in the cilia, which expressed α2-6-linked sialic acid only in the folds. 26792378 13 112 theme terminal 1959:1966 arg1 Fuc 1968:1970 cytoplasmic terminal Fuc 1947:1970 cytoplasmic terminal Fuc 1947:1970 After superovulation treatment, NCs expressed cytoplasmic terminal Fuc, βGalNAc, lactosamine, α2-3-, and α2-6-linked sialic acids in the folds. 25703052 5 0 from assay 786:790 arg1 incompatible 730:741 incompatible 730:741 incompatible 730:741 Enzymatic deglycosylation was incompatible with activity measurements in a cell based assay. 25703052 7 1 theme IL-7 1005:1008 arg1 yield 966:970 the yield 962:970 the yield of biologically active monomeric IL-7 962:1008 A chromatographic purification step between inclusion body solubilization and refolding increased the yield of biologically active monomeric IL-7, and decreased the amount of inactive soluble aggregates. 25703052 1 2 theme cytokine 148:155 arg1 mutants 157:163 cytokine mutants 148:163 cytokine mutants 148:163 The large scale screening of cytokine mutants is a component of binding and activity mapping and requires an efficient method of cytokine protein expression. 25703052 9 3 theme chromatographic 1334:1348 arg1 step 1363:1366 a chromatographic purification step 1332:1366 a chromatographic purification step of IL-7 solubilized from E. coli inclusion bodies 1332:1416 We conclude that a chromatographic purification step of IL-7 solubilized from E. coli inclusion bodies increases refolding yield, and may be a suitable general rescue strategy for obtaining folded and biologically active proteins from inclusion bodies. 25703052 8 4 theme untagged 1102:1109 arg1 IL-7 1111:1114 untagged IL-7 1102:1114 untagged IL-7 1102:1114 Cation exchange chromatography of untagged IL-7, and IMAC of His-tagged IL-7 improved refolding yields to a similar extend, indicating that the removal of contaminating components in the solubilized inclusion bodies improves refolding efficiency. 25703052 6 5 theme expressed 801:809 arg1 IL-7 811:814 E. coli expressed IL-7 793:814 E. coli expressed IL-7 793:814 E. coli expressed IL-7 was refolded from solubilized inclusion bodies. 25703052 1 6 theme mutants 157:163 arg1 component 170:178 a component 168:178 a component of binding and activity mapping 168:210 The large scale screening of cytokine mutants is a component of binding and activity mapping and requires an efficient method of cytokine protein expression. 25703052 1 6 theme mutants 157:163 arg1 screening 135:143 The large scale screening 119:143 The large scale screening of cytokine mutants 119:163 The large scale screening of cytokine mutants is a component of binding and activity mapping and requires an efficient method of cytokine protein expression. 25703052 9 7 theme active 1529:1534 arg1 proteins 1536:1543 folded and biologically active proteins 1505:1543 folded and biologically active proteins 1505:1543 We conclude that a chromatographic purification step of IL-7 solubilized from E. coli inclusion bodies increases refolding yield, and may be a suitable general rescue strategy for obtaining folded and biologically active proteins from inclusion bodies. 25703052 5 8 theme Enzymatic 700:708 arg1 deglycosylation 710:724 Enzymatic deglycosylation 700:724 Enzymatic deglycosylation 700:724 Enzymatic deglycosylation was incompatible with activity measurements in a cell based assay. 25703052 7 9 theme active 988:993 arg1 IL-7 1005:1008 biologically active monomeric IL-7 975:1008 biologically active monomeric IL-7 975:1008 A chromatographic purification step between inclusion body solubilization and refolding increased the yield of biologically active monomeric IL-7, and decreased the amount of inactive soluble aggregates. 25703052 6 10 theme coli 796:799 arg1 IL-7 811:814 E. coli expressed IL-7 793:814 E. coli expressed IL-7 793:814 E. coli expressed IL-7 was refolded from solubilized inclusion bodies. 25703052 8 11 theme His-tagged 1129:1138 arg1 IL-7 1140:1143 His-tagged IL-7 1129:1143 His-tagged IL-7 1129:1143 Cation exchange chromatography of untagged IL-7, and IMAC of His-tagged IL-7 improved refolding yields to a similar extend, indicating that the removal of contaminating components in the solubilized inclusion bodies improves refolding efficiency. 25703052 7 12 theme chromatographic 866:880 arg1 step 895:898 A chromatographic purification step 864:898 A chromatographic purification step between inclusion body solubilization and refolding 864:950 A chromatographic purification step between inclusion body solubilization and refolding increased the yield of biologically active monomeric IL-7, and decreased the amount of inactive soluble aggregates. 25703052 1 13 theme cytokine 248:255 arg1 expression 265:274 cytokine protein expression 248:274 cytokine protein expression 248:274 The large scale screening of cytokine mutants is a component of binding and activity mapping and requires an efficient method of cytokine protein expression. 25703052 9 14 theme inclusion 1550:1558 arg1 bodies 1560:1565 inclusion bodies 1550:1565 inclusion bodies 1550:1565 We conclude that a chromatographic purification step of IL-7 solubilized from E. coli inclusion bodies increases refolding yield, and may be a suitable general rescue strategy for obtaining folded and biologically active proteins from inclusion bodies. 25703052 6 15 theme E. 793:794 arg1 IL-7 811:814 E. coli expressed IL-7 793:814 E. coli expressed IL-7 793:814 E. coli expressed IL-7 was refolded from solubilized inclusion bodies. 25703052 1 16 theme protein 257:263 arg1 expression 265:274 cytokine protein expression 248:274 cytokine protein expression 248:274 The large scale screening of cytokine mutants is a component of binding and activity mapping and requires an efficient method of cytokine protein expression. 25703052 9 17 theme purification 1350:1361 arg1 step 1363:1366 a chromatographic purification step 1332:1366 a chromatographic purification step of IL-7 solubilized from E. coli inclusion bodies 1332:1416 We conclude that a chromatographic purification step of IL-7 solubilized from E. coli inclusion bodies increases refolding yield, and may be a suitable general rescue strategy for obtaining folded and biologically active proteins from inclusion bodies. 25703052 8 18 theme exchange 1075:1082 arg1 chromatography 1084:1097 Cation exchange chromatography 1068:1097 Cation exchange chromatography of untagged IL-7 1068:1114 Cation exchange chromatography of untagged IL-7, and IMAC of His-tagged IL-7 improved refolding yields to a similar extend, indicating that the removal of contaminating components in the solubilized inclusion bodies improves refolding efficiency. 25703052 3 19 contain contains 406:413 arg1 cytokine 397:404 The IL-7 cytokine 388:404 The IL-7 cytokine 388:404 The IL-7 cytokine contains three disulfide bonds that are essential for its biological activity, and which are formed upon secretion through P. pastoris, but not in the reducing cytoplasm of E. coli. 25703052 3 19 contain contains 406:413 arg2 bonds 431:435 three disulfide bonds 415:435 three disulfide bonds that are essential for its biological activity, and which are formed upon secretion through P. pastoris, but not in the reducing cytoplasm of E. coli 415:585 The IL-7 cytokine contains three disulfide bonds that are essential for its biological activity, and which are formed upon secretion through P. pastoris, but not in the reducing cytoplasm of E. coli. 25703052 9 20 theme suitable 1458:1465 arg1 strategy 1482:1489 a suitable general rescue strategy 1456:1489 a suitable general rescue strategy for obtaining folded and biologically active proteins from inclusion bodies 1456:1565 We conclude that a chromatographic purification step of IL-7 solubilized from E. coli inclusion bodies increases refolding yield, and may be a suitable general rescue strategy for obtaining folded and biologically active proteins from inclusion bodies. 25703052 8 21 theme solubilized 1255:1265 arg1 bodies 1277:1282 the solubilized inclusion bodies 1251:1282 the solubilized inclusion bodies 1251:1282 Cation exchange chromatography of untagged IL-7, and IMAC of His-tagged IL-7 improved refolding yields to a similar extend, indicating that the removal of contaminating components in the solubilized inclusion bodies improves refolding efficiency. 25703052 8 22 theme components 1237:1246 arg1 removal 1212:1218 the removal 1208:1218 the removal of contaminating components in the solubilized inclusion bodies 1208:1282 Cation exchange chromatography of untagged IL-7, and IMAC of His-tagged IL-7 improved refolding yields to a similar extend, indicating that the removal of contaminating components in the solubilized inclusion bodies improves refolding efficiency. 25703052 8 23 theme Cation 1068:1073 arg1 chromatography 1084:1097 Cation exchange chromatography 1068:1097 Cation exchange chromatography of untagged IL-7 1068:1114 Cation exchange chromatography of untagged IL-7, and IMAC of His-tagged IL-7 improved refolding yields to a similar extend, indicating that the removal of contaminating components in the solubilized inclusion bodies improves refolding efficiency. 25703052 6 24 theme solubilized 834:844 arg1 bodies 856:861 solubilized inclusion bodies 834:861 solubilized inclusion bodies 834:861 E. coli expressed IL-7 was refolded from solubilized inclusion bodies. 25703052 4 25 link N-linked 667:674 arg1 IL-7 694:697 active but N-linked hyperglycosylated IL-7 656:697 active but N-linked hyperglycosylated IL-7 656:697 In contrast to a previous report we found that P. pastoris secretes active but N-linked hyperglycosylated IL-7. 25703052 9 26 theme rescue 1475:1480 arg1 strategy 1482:1489 a suitable general rescue strategy 1456:1489 a suitable general rescue strategy for obtaining folded and biologically active proteins from inclusion bodies 1456:1565 We conclude that a chromatographic purification step of IL-7 solubilized from E. coli inclusion bodies increases refolding yield, and may be a suitable general rescue strategy for obtaining folded and biologically active proteins from inclusion bodies. 25703052 8 27 dep similar 1176:1182 arg1 extend 1184:1189 extend 1184:1189 extend 1184:1189 Cation exchange chromatography of untagged IL-7, and IMAC of His-tagged IL-7 improved refolding yields to a similar extend, indicating that the removal of contaminating components in the solubilized inclusion bodies improves refolding efficiency. 25703052 9 28 theme IL-7 1371:1374 arg1 step 1363:1366 a chromatographic purification step 1332:1366 a chromatographic purification step of IL-7 solubilized from E. coli inclusion bodies 1332:1416 We conclude that a chromatographic purification step of IL-7 solubilized from E. coli inclusion bodies increases refolding yield, and may be a suitable general rescue strategy for obtaining folded and biologically active proteins from inclusion bodies. 25703052 2 29 theme IL-7 307:310 arg1 expression 312:321 recombinant IL-7 expression 295:321 recombinant IL-7 expression 295:321 Here, we compared recombinant IL-7 expression with and purification from Escherichia coli and Pichia pastoris. 25703052 3 30 theme disulfide 421:429 arg1 bonds 431:435 three disulfide bonds 415:435 three disulfide bonds that are essential for its biological activity, and which are formed upon secretion through P. pastoris, but not in the reducing cytoplasm of E. coli 415:585 The IL-7 cytokine contains three disulfide bonds that are essential for its biological activity, and which are formed upon secretion through P. pastoris, but not in the reducing cytoplasm of E. coli. 25703052 1 31 theme expression 265:274 arg1 method 238:243 an efficient method 225:243 an efficient method of cytokine protein expression 225:274 The large scale screening of cytokine mutants is a component of binding and activity mapping and requires an efficient method of cytokine protein expression. 25703052 2 32 theme recombinant 295:305 arg1 expression 312:321 recombinant IL-7 expression 295:321 recombinant IL-7 expression 295:321 Here, we compared recombinant IL-7 expression with and purification from Escherichia coli and Pichia pastoris. 25703052 8 33 theme inclusion 1267:1275 arg1 bodies 1277:1282 the solubilized inclusion bodies 1251:1282 the solubilized inclusion bodies 1251:1282 Cation exchange chromatography of untagged IL-7, and IMAC of His-tagged IL-7 improved refolding yields to a similar extend, indicating that the removal of contaminating components in the solubilized inclusion bodies improves refolding efficiency. 25703052 0 34 theme purification 18:29 arg1 Comparison 0:9 Comparison 0:9 Comparison of the purification of biologically active IL-7 cytokine 0:66 Comparison of the purification of biologically active IL-7 cytokine expressed in Escherichia coli and Pichia pastoris. 25703052 3 35 theme coli 582:585 arg1 cytoplasm 566:574 the reducing cytoplasm 553:574 the reducing cytoplasm of E. coli 553:585 The IL-7 cytokine contains three disulfide bonds that are essential for its biological activity, and which are formed upon secretion through P. pastoris, but not in the reducing cytoplasm of E. coli. 25703052 8 36 theme IL-7 1111:1114 arg1 chromatography 1084:1097 Cation exchange chromatography 1068:1097 Cation exchange chromatography of untagged IL-7 1068:1114 Cation exchange chromatography of untagged IL-7, and IMAC of His-tagged IL-7 improved refolding yields to a similar extend, indicating that the removal of contaminating components in the solubilized inclusion bodies improves refolding efficiency. 25703052 8 36 theme IL-7 1111:1114 arg1 IMAC 1121:1124 IMAC 1121:1124 IMAC of His-tagged IL-7 1121:1143 Cation exchange chromatography of untagged IL-7, and IMAC of His-tagged IL-7 improved refolding yields to a similar extend, indicating that the removal of contaminating components in the solubilized inclusion bodies improves refolding efficiency. 25703052 2 37 from coli 362:365 arg1 purification 332:343 and purification 328:343 purification 332:343 Here, we compared recombinant IL-7 expression with and purification from Escherichia coli and Pichia pastoris. 25703052 5 38 theme based 780:784 arg1 assay 786:790 a cell based assay 773:790 a cell based assay 773:790 Enzymatic deglycosylation was incompatible with activity measurements in a cell based assay. 25703052 9 39 theme general 1467:1473 arg1 strategy 1482:1489 a suitable general rescue strategy 1456:1489 a suitable general rescue strategy for obtaining folded and biologically active proteins from inclusion bodies 1456:1565 We conclude that a chromatographic purification step of IL-7 solubilized from E. coli inclusion bodies increases refolding yield, and may be a suitable general rescue strategy for obtaining folded and biologically active proteins from inclusion bodies. 25703052 1 40 theme binding 183:189 arg1 component 170:178 a component 168:178 a component of binding and activity mapping 168:210 The large scale screening of cytokine mutants is a component of binding and activity mapping and requires an efficient method of cytokine protein expression. 25703052 1 40 theme binding 183:189 arg1 screening 135:143 The large scale screening 119:143 The large scale screening of cytokine mutants 119:163 The large scale screening of cytokine mutants is a component of binding and activity mapping and requires an efficient method of cytokine protein expression. 25703052 4 41 gly hyperglycosylated 676:692 arg1 IL-7 694:697 active but N-linked hyperglycosylated IL-7 656:697 active but N-linked hyperglycosylated IL-7 656:697 In contrast to a previous report we found that P. pastoris secretes active but N-linked hyperglycosylated IL-7. 25703052 4 42 theme active 656:661 arg1 IL-7 694:697 active but N-linked hyperglycosylated IL-7 656:697 active but N-linked hyperglycosylated IL-7 656:697 In contrast to a previous report we found that P. pastoris secretes active but N-linked hyperglycosylated IL-7. 25703052 3 43 theme biological 464:473 arg1 activity 475:482 its biological activity 460:482 its biological activity 460:482 The IL-7 cytokine contains three disulfide bonds that are essential for its biological activity, and which are formed upon secretion through P. pastoris, but not in the reducing cytoplasm of E. coli. 25703052 8 44 theme contaminating 1223:1235 arg1 components 1237:1246 contaminating components 1223:1246 contaminating components 1223:1246 Cation exchange chromatography of untagged IL-7, and IMAC of His-tagged IL-7 improved refolding yields to a similar extend, indicating that the removal of contaminating components in the solubilized inclusion bodies improves refolding efficiency. 25703052 9 45 theme E. 1393:1394 arg1 bodies 1411:1416 E. coli inclusion bodies 1393:1416 E. coli inclusion bodies 1393:1416 We conclude that a chromatographic purification step of IL-7 solubilized from E. coli inclusion bodies increases refolding yield, and may be a suitable general rescue strategy for obtaining folded and biologically active proteins from inclusion bodies. 25703052 9 46 dep E. 1393:1394 arg1 coli 1396:1399 coli 1396:1399 coli 1396:1399 We conclude that a chromatographic purification step of IL-7 solubilized from E. coli inclusion bodies increases refolding yield, and may be a suitable general rescue strategy for obtaining folded and biologically active proteins from inclusion bodies. 25703052 5 47 from incompatible 730:741 arg1 assay 786:790 a cell based assay 773:790 a cell based assay 773:790 Enzymatic deglycosylation was incompatible with activity measurements in a cell based assay. 25703052 4 48 dep report 614:619 arg1 contrast 591:598 contrast 591:598 contrast 591:598 In contrast to a previous report we found that P. pastoris secretes active but N-linked hyperglycosylated IL-7. 25703052 7 49 dep active 988:993 arg1 monomeric 995:1003 monomeric 995:1003 monomeric 995:1003 A chromatographic purification step between inclusion body solubilization and refolding increased the yield of biologically active monomeric IL-7, and decreased the amount of inactive soluble aggregates. 25703052 1 50 theme activity 195:202 arg1 component 170:178 a component 168:178 a component of binding and activity mapping 168:210 The large scale screening of cytokine mutants is a component of binding and activity mapping and requires an efficient method of cytokine protein expression. 25703052 1 50 theme activity 195:202 arg1 screening 135:143 The large scale screening 119:143 The large scale screening of cytokine mutants 119:163 The large scale screening of cytokine mutants is a component of binding and activity mapping and requires an efficient method of cytokine protein expression. 25703052 5 51 theme cell 775:778 arg1 assay 786:790 a cell based assay 773:790 a cell based assay 773:790 Enzymatic deglycosylation was incompatible with activity measurements in a cell based assay. 25703052 6 52 theme inclusion 846:854 arg1 bodies 856:861 solubilized inclusion bodies 834:861 solubilized inclusion bodies 834:861 E. coli expressed IL-7 was refolded from solubilized inclusion bodies. 25703052 5 53 with incompatible 730:741 arg1 measurements 757:768 activity measurements 748:768 activity measurements 748:768 Enzymatic deglycosylation was incompatible with activity measurements in a cell based assay. 25703052 2 54 from pastoris 378:385 arg1 purification 332:343 and purification 328:343 purification 332:343 Here, we compared recombinant IL-7 expression with and purification from Escherichia coli and Pichia pastoris. 25703052 4 55 theme previous 605:612 arg1 report 614:619 a previous report 603:619 a previous report 603:619 In contrast to a previous report we found that P. pastoris secretes active but N-linked hyperglycosylated IL-7. 25703052 3 56 theme IL-7 392:395 arg1 cytokine 397:404 The IL-7 cytokine 388:404 The IL-7 cytokine 388:404 The IL-7 cytokine contains three disulfide bonds that are essential for its biological activity, and which are formed upon secretion through P. pastoris, but not in the reducing cytoplasm of E. coli. 25703052 9 57 theme inclusion 1401:1409 arg1 bodies 1411:1416 E. coli inclusion bodies 1393:1416 E. coli inclusion bodies 1393:1416 We conclude that a chromatographic purification step of IL-7 solubilized from E. coli inclusion bodies increases refolding yield, and may be a suitable general rescue strategy for obtaining folded and biologically active proteins from inclusion bodies. 25703052 7 58 theme aggregates 1056:1065 arg1 aggregates 1056:1065 inactive soluble aggregates 1039:1065 inactive soluble aggregates 1039:1065 A chromatographic purification step between inclusion body solubilization and refolding increased the yield of biologically active monomeric IL-7, and decreased the amount of inactive soluble aggregates. 25703052 7 58 theme aggregates 1056:1065 arg1 amount 1029:1034 the amount 1025:1034 the amount of inactive soluble aggregates 1025:1065 A chromatographic purification step between inclusion body solubilization and refolding increased the yield of biologically active monomeric IL-7, and decreased the amount of inactive soluble aggregates. 25703052 0 59 theme cytokine 59:66 arg1 purification 18:29 the purification 14:29 the purification of biologically active IL-7 cytokine 14:66 Comparison of the purification of biologically active IL-7 cytokine expressed in Escherichia coli and Pichia pastoris. 25703052 3 60 theme reducing 557:564 arg1 cytoplasm 566:574 the reducing cytoplasm 553:574 the reducing cytoplasm of E. coli 553:585 The IL-7 cytokine contains three disulfide bonds that are essential for its biological activity, and which are formed upon secretion through P. pastoris, but not in the reducing cytoplasm of E. coli. 25703052 8 61 theme IL-7 1140:1143 arg1 chromatography 1084:1097 Cation exchange chromatography 1068:1097 Cation exchange chromatography of untagged IL-7 1068:1114 Cation exchange chromatography of untagged IL-7, and IMAC of His-tagged IL-7 improved refolding yields to a similar extend, indicating that the removal of contaminating components in the solubilized inclusion bodies improves refolding efficiency. 25703052 8 61 theme IL-7 1140:1143 arg1 IMAC 1121:1124 IMAC 1121:1124 IMAC of His-tagged IL-7 1121:1143 Cation exchange chromatography of untagged IL-7, and IMAC of His-tagged IL-7 improved refolding yields to a similar extend, indicating that the removal of contaminating components in the solubilized inclusion bodies improves refolding efficiency. 25703052 4 62 theme hyperglycosylated 676:692 arg1 IL-7 694:697 active but N-linked hyperglycosylated IL-7 656:697 active but N-linked hyperglycosylated IL-7 656:697 In contrast to a previous report we found that P. pastoris secretes active but N-linked hyperglycosylated IL-7. 25703052 0 63 theme active 47:52 arg1 cytokine 59:66 biologically active IL-7 cytokine 34:66 biologically active IL-7 cytokine 34:66 Comparison of the purification of biologically active IL-7 cytokine expressed in Escherichia coli and Pichia pastoris. 25703052 8 64 attach removal 1212:1218 arg2 components 1237:1246 contaminating components 1223:1246 contaminating components 1223:1246 Cation exchange chromatography of untagged IL-7, and IMAC of His-tagged IL-7 improved refolding yields to a similar extend, indicating that the removal of contaminating components in the solubilized inclusion bodies improves refolding efficiency. 25703052 8 64 attach removal 1212:1218 arg3 bodies 1277:1282 the solubilized inclusion bodies 1251:1282 the solubilized inclusion bodies 1251:1282 Cation exchange chromatography of untagged IL-7, and IMAC of His-tagged IL-7 improved refolding yields to a similar extend, indicating that the removal of contaminating components in the solubilized inclusion bodies improves refolding efficiency. 25703052 9 65 theme folded 1505:1510 arg1 proteins 1536:1543 folded and biologically active proteins 1505:1543 folded and biologically active proteins 1505:1543 We conclude that a chromatographic purification step of IL-7 solubilized from E. coli inclusion bodies increases refolding yield, and may be a suitable general rescue strategy for obtaining folded and biologically active proteins from inclusion bodies. 25703052 4 66 theme N-linked 667:674 arg1 IL-7 694:697 active but N-linked hyperglycosylated IL-7 656:697 active but N-linked hyperglycosylated IL-7 656:697 In contrast to a previous report we found that P. pastoris secretes active but N-linked hyperglycosylated IL-7. 25703052 7 67 theme body 918:921 arg1 solubilization 923:936 inclusion body solubilization 908:936 inclusion body solubilization 908:936 A chromatographic purification step between inclusion body solubilization and refolding increased the yield of biologically active monomeric IL-7, and decreased the amount of inactive soluble aggregates. 25703052 7 68 theme inactive 1039:1046 arg1 aggregates 1056:1065 inactive soluble aggregates 1039:1065 inactive soluble aggregates 1039:1065 A chromatographic purification step between inclusion body solubilization and refolding increased the yield of biologically active monomeric IL-7, and decreased the amount of inactive soluble aggregates. 25703052 5 69 theme activity 748:755 arg1 measurements 757:768 activity measurements 748:768 activity measurements 748:768 Enzymatic deglycosylation was incompatible with activity measurements in a cell based assay. 25703052 1 70 theme large 123:127 arg1 component 170:178 a component 168:178 a component of binding and activity mapping 168:210 The large scale screening of cytokine mutants is a component of binding and activity mapping and requires an efficient method of cytokine protein expression. 25703052 1 70 theme large 123:127 arg1 screening 135:143 The large scale screening 119:143 The large scale screening of cytokine mutants 119:163 The large scale screening of cytokine mutants is a component of binding and activity mapping and requires an efficient method of cytokine protein expression. 25703052 9 71 theme refolding 1428:1436 arg1 yield 1438:1442 refolding yield 1428:1442 refolding yield 1428:1442 We conclude that a chromatographic purification step of IL-7 solubilized from E. coli inclusion bodies increases refolding yield, and may be a suitable general rescue strategy for obtaining folded and biologically active proteins from inclusion bodies. 25703052 7 72 theme soluble 1048:1054 arg1 aggregates 1056:1065 inactive soluble aggregates 1039:1065 inactive soluble aggregates 1039:1065 A chromatographic purification step between inclusion body solubilization and refolding increased the yield of biologically active monomeric IL-7, and decreased the amount of inactive soluble aggregates. 25703052 1 73 theme scale 129:133 arg1 component 170:178 a component 168:178 a component of binding and activity mapping 168:210 The large scale screening of cytokine mutants is a component of binding and activity mapping and requires an efficient method of cytokine protein expression. 25703052 1 73 theme scale 129:133 arg1 screening 135:143 The large scale screening 119:143 The large scale screening of cytokine mutants 119:163 The large scale screening of cytokine mutants is a component of binding and activity mapping and requires an efficient method of cytokine protein expression. 25703052 8 74 theme refolding 1154:1162 arg1 yields 1164:1169 refolding yields 1154:1169 refolding yields 1154:1169 Cation exchange chromatography of untagged IL-7, and IMAC of His-tagged IL-7 improved refolding yields to a similar extend, indicating that the removal of contaminating components in the solubilized inclusion bodies improves refolding efficiency. 25703052 1 75 dep binding 183:189 arg1 mapping 204:210 mapping 204:210 mapping 204:210 The large scale screening of cytokine mutants is a component of binding and activity mapping and requires an efficient method of cytokine protein expression. 25703052 8 76 theme refolding 1293:1301 arg1 efficiency 1303:1312 refolding efficiency 1293:1312 refolding efficiency 1293:1312 Cation exchange chromatography of untagged IL-7, and IMAC of His-tagged IL-7 improved refolding yields to a similar extend, indicating that the removal of contaminating components in the solubilized inclusion bodies improves refolding efficiency. 25703052 7 77 theme inclusion 908:916 arg1 solubilization 923:936 inclusion body solubilization 908:936 inclusion body solubilization 908:936 A chromatographic purification step between inclusion body solubilization and refolding increased the yield of biologically active monomeric IL-7, and decreased the amount of inactive soluble aggregates. 25703052 0 78 theme IL-7 54:57 arg1 cytokine 59:66 biologically active IL-7 cytokine 34:66 biologically active IL-7 cytokine 34:66 Comparison of the purification of biologically active IL-7 cytokine expressed in Escherichia coli and Pichia pastoris. 25703052 8 79 from removal 1212:1218 arg1 bodies 1277:1282 the solubilized inclusion bodies 1251:1282 the solubilized inclusion bodies 1251:1282 Cation exchange chromatography of untagged IL-7, and IMAC of His-tagged IL-7 improved refolding yields to a similar extend, indicating that the removal of contaminating components in the solubilized inclusion bodies improves refolding efficiency. 25703052 7 80 theme purification 882:893 arg1 step 895:898 A chromatographic purification step 864:898 A chromatographic purification step between inclusion body solubilization and refolding 864:950 A chromatographic purification step between inclusion body solubilization and refolding increased the yield of biologically active monomeric IL-7, and decreased the amount of inactive soluble aggregates. 25703052 1 81 theme efficient 228:236 arg1 method 238:243 an efficient method 225:243 an efficient method of cytokine protein expression 225:274 The large scale screening of cytokine mutants is a component of binding and activity mapping and requires an efficient method of cytokine protein expression. 25510854 3 0 theme glycoproteins 644:656 arg1 receptors 625:633 receptors 625:633 receptors of CLEC2 glycoproteins 625:656 Most NKRP1 molecules are expressed on NK cells and T cells and act as receptors of CLEC2 glycoproteins with their genes being intermingled in a certain sub-region of the mammalian NKC. 25510854 3 0 theme glycoproteins 644:656 arg1 molecules 566:574 Most NKRP1 molecules 555:574 Most NKRP1 molecules 555:574 Most NKRP1 molecules are expressed on NK cells and T cells and act as receptors of CLEC2 glycoproteins with their genes being intermingled in a certain sub-region of the mammalian NKC. 25510854 9 1 theme functional 1608:1617 arg1 recognition 1619:1629 functional recognition 1608:1629 functional recognition of these KACL mutants by NK-92M-NKp65 cells 1608:1673 Accordingly, functional recognition of these KACL mutants by NK-92M-NKp65 cells was completely abolished. 25510854 0 2 theme high-affinity 184:196 arg1 NKp65 207:211 its high-affinity receptor NKp65 180:211 its high-affinity receptor NKp65 180:211 Key residues at the membrane-distal surface of KACL, but not glycosylation, determine the functional interaction of the keratinocyte-specific C-type lectin-like receptor KACL with its high-affinity receptor NKp65. 25510854 1 3 theme C-type 273:278 arg1 lectin 245:250 Keratinocyte-associated C-type lectin 214:250 Keratinocyte-associated C-type lectin (KACL) 214:257 Keratinocyte-associated C-type lectin (KACL) is a peculiar C-type lectin-like receptor (CTLR) due to its selective expression by human keratinocytes and cognate interaction with the genetically coupled CTLR NKp65. 25510854 1 3 theme C-type 273:278 arg1 CTLR 302:305 CTLR 302:305 CTLR 302:305 Keratinocyte-associated C-type lectin (KACL) is a peculiar C-type lectin-like receptor (CTLR) due to its selective expression by human keratinocytes and cognate interaction with the genetically coupled CTLR NKp65. 25510854 1 3 theme C-type 273:278 arg1 receptor 292:299 a peculiar C-type lectin-like receptor 262:299 a peculiar C-type lectin-like receptor (CTLR) 262:306 Keratinocyte-associated C-type lectin (KACL) is a peculiar C-type lectin-like receptor (CTLR) due to its selective expression by human keratinocytes and cognate interaction with the genetically coupled CTLR NKp65. 25510854 4 4 theme receptor/ligand 801:815 arg1 pairs 817:821 these dedicated receptor/ligand pairs 785:821 these dedicated receptor/ligand pairs 785:821 The reasons for the tight genetic linkage of these dedicated receptor/ligand pairs are unknown, as is the physiological expression of NKp65. 25510854 6 5 theme KACL-specific 1122:1134 arg1 mAb 1159:1161 mAb 1159:1161 mAb 1159:1161 Here, we address the molecular basis of this high-affinity interaction by analysing KACL mutants with KACL-specific monoclonal antibodies (mAb), soluble NKp65 (sNKp65) and NK-92MI-NKp65 cells. 25510854 6 5 theme KACL-specific 1122:1134 arg1 antibodies 1147:1156 KACL-specific monoclonal antibodies 1122:1156 KACL-specific monoclonal antibodies (mAb) 1122:1162 Here, we address the molecular basis of this high-affinity interaction by analysing KACL mutants with KACL-specific monoclonal antibodies (mAb), soluble NKp65 (sNKp65) and NK-92MI-NKp65 cells. 25510854 6 6 theme NK-92MI-NKp65 1192:1204 arg1 cells 1206:1210 NK-92MI-NKp65 cells 1192:1210 NK-92MI-NKp65 cells 1192:1210 Here, we address the molecular basis of this high-affinity interaction by analysing KACL mutants with KACL-specific monoclonal antibodies (mAb), soluble NKp65 (sNKp65) and NK-92MI-NKp65 cells. 25510854 9 7 theme KACL 1640:1643 arg1 mutants 1645:1651 these KACL mutants 1634:1651 these KACL mutants 1634:1651 Accordingly, functional recognition of these KACL mutants by NK-92M-NKp65 cells was completely abolished. 25510854 10 8 theme KACL 1886:1889 arg1 glycosylation 1891:1903 KACL glycosylation 1886:1903 KACL glycosylation 1886:1903 Arginine 158 and isoleucine 161 located at the membrane-distal surface of KACL were defined as residues, decisively determining functional KACL-NKp65 interaction that is independent of KACL glycosylation. 25510854 3 9 theme Most 555:558 arg1 receptors 625:633 receptors 625:633 receptors of CLEC2 glycoproteins 625:656 Most NKRP1 molecules are expressed on NK cells and T cells and act as receptors of CLEC2 glycoproteins with their genes being intermingled in a certain sub-region of the mammalian NKC. 25510854 3 9 theme Most 555:558 arg1 molecules 566:574 Most NKRP1 molecules 555:574 Most NKRP1 molecules 555:574 Most NKRP1 molecules are expressed on NK cells and T cells and act as receptors of CLEC2 glycoproteins with their genes being intermingled in a certain sub-region of the mammalian NKC. 25510854 7 10 theme surface 1323:1329 arg1 expression 1331:1340 KACL surface expression 1318:1340 KACL surface expression 1318:1340 We find that none of the three N-linked carbohydrates of KACL glycoproteins significantly contributes to KACL surface expression and NKp65 interaction. 25510854 7 11 theme NKp65 1346:1350 arg1 interaction 1352:1362 NKp65 interaction 1346:1362 NKp65 interaction 1346:1362 We find that none of the three N-linked carbohydrates of KACL glycoproteins significantly contributes to KACL surface expression and NKp65 interaction. 25510854 3 12 theme certain 699:705 arg1 sub-region 707:716 a certain sub-region 697:716 a certain sub-region of the mammalian NKC 697:737 Most NKRP1 molecules are expressed on NK cells and T cells and act as receptors of CLEC2 glycoproteins with their genes being intermingled in a certain sub-region of the mammalian NKC. 25510854 10 13 theme located 1733:1739 arg1 isoleucine 1718:1727 isoleucine 161 1718:1731 isoleucine 161 1718:1731 Arginine 158 and isoleucine 161 located at the membrane-distal surface of KACL were defined as residues, decisively determining functional KACL-NKp65 interaction that is independent of KACL glycosylation. 25510854 10 13 theme located 1733:1739 arg1 residues 1796:1803 residues 1796:1803 residues 1796:1803 Arginine 158 and isoleucine 161 located at the membrane-distal surface of KACL were defined as residues, decisively determining functional KACL-NKp65 interaction that is independent of KACL glycosylation. 25510854 10 13 theme located 1733:1739 arg1 Arginine 1701:1708 Arginine 158 1701:1712 Arginine 158 1701:1712 Arginine 158 and isoleucine 161 located at the membrane-distal surface of KACL were defined as residues, decisively determining functional KACL-NKp65 interaction that is independent of KACL glycosylation. 25510854 8 14 theme non-conservative 1392:1407 arg1 substitutions 1420:1432 non-conservative amino acid substitutions 1392:1432 non-conservative amino acid substitutions of arginine 158 or isoleucine 1392:1462 However, KACL mutants with non-conservative amino acid substitutions of arginine 158 or isoleucine 161 abrogated binding of both KACL-specific mAb OMA1 and sNKp65, well in line with the blockade of NKp65-KACL interaction by OMA1. 25510854 10 15 theme KACL 1775:1778 arg1 surface 1764:1770 the membrane-distal surface 1744:1770 the membrane-distal surface of KACL 1744:1778 Arginine 158 and isoleucine 161 located at the membrane-distal surface of KACL were defined as residues, decisively determining functional KACL-NKp65 interaction that is independent of KACL glycosylation. 25510854 1 16 theme C-type 238:243 arg1 KACL 253:256 KACL 253:256 KACL 253:256 Keratinocyte-associated C-type lectin (KACL) is a peculiar C-type lectin-like receptor (CTLR) due to its selective expression by human keratinocytes and cognate interaction with the genetically coupled CTLR NKp65. 25510854 1 16 theme C-type 238:243 arg1 lectin 245:250 Keratinocyte-associated C-type lectin 214:250 Keratinocyte-associated C-type lectin (KACL) 214:257 Keratinocyte-associated C-type lectin (KACL) is a peculiar C-type lectin-like receptor (CTLR) due to its selective expression by human keratinocytes and cognate interaction with the genetically coupled CTLR NKp65. 25510854 1 16 theme C-type 238:243 arg1 receptor 292:299 a peculiar C-type lectin-like receptor 262:299 a peculiar C-type lectin-like receptor (CTLR) 262:306 Keratinocyte-associated C-type lectin (KACL) is a peculiar C-type lectin-like receptor (CTLR) due to its selective expression by human keratinocytes and cognate interaction with the genetically coupled CTLR NKp65. 25510854 4 17 theme physiological 846:858 arg1 expression 860:869 the physiological expression 842:869 the physiological expression of NKp65 842:878 The reasons for the tight genetic linkage of these dedicated receptor/ligand pairs are unknown, as is the physiological expression of NKp65. 25510854 8 18 theme acid 1415:1418 arg1 substitutions 1420:1432 non-conservative amino acid substitutions 1392:1432 non-conservative amino acid substitutions of arginine 158 or isoleucine 1392:1462 However, KACL mutants with non-conservative amino acid substitutions of arginine 158 or isoleucine 161 abrogated binding of both KACL-specific mAb OMA1 and sNKp65, well in line with the blockade of NKp65-KACL interaction by OMA1. 25510854 7 19 theme KACL 1318:1321 arg1 expression 1331:1340 KACL surface expression 1318:1340 KACL surface expression 1318:1340 We find that none of the three N-linked carbohydrates of KACL glycoproteins significantly contributes to KACL surface expression and NKp65 interaction. 25510854 3 20 theme mammalian 725:733 arg1 NKC 735:737 the mammalian NKC 721:737 the mammalian NKC 721:737 Most NKRP1 molecules are expressed on NK cells and T cells and act as receptors of CLEC2 glycoproteins with their genes being intermingled in a certain sub-region of the mammalian NKC. 25510854 0 21 theme C-type 142:147 arg1 receptor 161:168 the keratinocyte-specific C-type lectin-like receptor 116:168 the keratinocyte-specific C-type lectin-like receptor KACL 116:173 Key residues at the membrane-distal surface of KACL, but not glycosylation, determine the functional interaction of the keratinocyte-specific C-type lectin-like receptor KACL with its high-affinity receptor NKp65. 25510854 1 22 theme CTLR 416:419 arg1 NKp65 421:425 the genetically coupled CTLR NKp65 392:425 the genetically coupled CTLR NKp65 392:425 Keratinocyte-associated C-type lectin (KACL) is a peculiar C-type lectin-like receptor (CTLR) due to its selective expression by human keratinocytes and cognate interaction with the genetically coupled CTLR NKp65. 25510854 0 23 theme receptor 161:168 arg1 KACL 170:173 the keratinocyte-specific C-type lectin-like receptor KACL 116:173 the keratinocyte-specific C-type lectin-like receptor KACL 116:173 Key residues at the membrane-distal surface of KACL, but not glycosylation, determine the functional interaction of the keratinocyte-specific C-type lectin-like receptor KACL with its high-affinity receptor NKp65. 25510854 5 24 theme NK-92MI 1005:1011 arg1 cells 1013:1017 NKp65-expressing NK-92MI cells 988:1017 NKp65-expressing NK-92MI cells 988:1017 Recently, we reported that the CTLR NKp65 and KACL interact with high affinity, resulting in activation of NKp65-expressing NK-92MI cells. 25510854 8 25 with line 1537:1540 arg1 blockade 1551:1558 the blockade 1547:1558 the blockade of NKp65-KACL interaction by OMA1 1547:1592 However, KACL mutants with non-conservative amino acid substitutions of arginine 158 or isoleucine 161 abrogated binding of both KACL-specific mAb OMA1 and sNKp65, well in line with the blockade of NKp65-KACL interaction by OMA1. 25510854 2 26 theme natural 493:499 arg1 killer 501:506 natural killer 493:506 natural killer gene complex (NKC)-encoded CTLR, respectively 493:552 KACL and NKp65 are members of the CLEC2 and NKRP1 subfamilies of natural killer gene complex (NKC)-encoded CTLR, respectively. 25510854 7 27 theme glycoproteins 1275:1287 arg1 carbohydrates 1253:1265 the three N-linked carbohydrates 1234:1265 the three N-linked carbohydrates of KACL glycoproteins 1234:1287 We find that none of the three N-linked carbohydrates of KACL glycoproteins significantly contributes to KACL surface expression and NKp65 interaction. 25510854 0 28 with interaction 101:111 arg1 NKp65 207:211 its high-affinity receptor NKp65 180:211 its high-affinity receptor NKp65 180:211 Key residues at the membrane-distal surface of KACL, but not glycosylation, determine the functional interaction of the keratinocyte-specific C-type lectin-like receptor KACL with its high-affinity receptor NKp65. 25510854 1 29 theme selective 319:327 arg1 expression 329:338 its selective expression 315:338 its selective expression by human keratinocytes 315:361 Keratinocyte-associated C-type lectin (KACL) is a peculiar C-type lectin-like receptor (CTLR) due to its selective expression by human keratinocytes and cognate interaction with the genetically coupled CTLR NKp65. 25510854 3 30 theme NK 593:594 arg1 cells 596:600 NK cells 593:600 NK cells 593:600 Most NKRP1 molecules are expressed on NK cells and T cells and act as receptors of CLEC2 glycoproteins with their genes being intermingled in a certain sub-region of the mammalian NKC. 25510854 9 31 theme NK-92M-NKp65 1656:1667 arg1 cells 1669:1673 NK-92M-NKp65 cells 1656:1673 NK-92M-NKp65 cells 1656:1673 Accordingly, functional recognition of these KACL mutants by NK-92M-NKp65 cells was completely abolished. 25510854 2 32 theme subfamilies 478:488 arg1 members 447:453 members 447:453 members of the CLEC2 and NKRP1 subfamilies of natural killer gene complex (NKC)-encoded CTLR, respectively 447:552 KACL and NKp65 are members of the CLEC2 and NKRP1 subfamilies of natural killer gene complex (NKC)-encoded CTLR, respectively. 25510854 2 32 theme subfamilies 478:488 arg1 NKp65 437:441 NKp65 437:441 NKp65 437:441 KACL and NKp65 are members of the CLEC2 and NKRP1 subfamilies of natural killer gene complex (NKC)-encoded CTLR, respectively. 25510854 2 32 theme subfamilies 478:488 arg1 KACL 428:431 KACL 428:431 KACL 428:431 KACL and NKp65 are members of the CLEC2 and NKRP1 subfamilies of natural killer gene complex (NKC)-encoded CTLR, respectively. 25510854 8 33 theme isoleucine 1453:1462 arg1 substitutions 1420:1432 non-conservative amino acid substitutions 1392:1432 non-conservative amino acid substitutions of arginine 158 or isoleucine 1392:1462 However, KACL mutants with non-conservative amino acid substitutions of arginine 158 or isoleucine 161 abrogated binding of both KACL-specific mAb OMA1 and sNKp65, well in line with the blockade of NKp65-KACL interaction by OMA1. 25510854 2 34 theme gene 508:511 arg1 NKC 522:524 NKC 522:524 NKC 522:524 KACL and NKp65 are members of the CLEC2 and NKRP1 subfamilies of natural killer gene complex (NKC)-encoded CTLR, respectively. 25510854 2 34 theme gene 508:511 arg1 complex 513:519 natural killer gene complex 493:519 natural killer gene complex (NKC)-encoded CTLR, respectively 493:552 KACL and NKp65 are members of the CLEC2 and NKRP1 subfamilies of natural killer gene complex (NKC)-encoded CTLR, respectively. 25510854 1 35 theme cognate 367:373 arg1 interaction 375:385 cognate interaction 367:385 cognate interaction with the genetically coupled CTLR NKp65 367:425 Keratinocyte-associated C-type lectin (KACL) is a peculiar C-type lectin-like receptor (CTLR) due to its selective expression by human keratinocytes and cognate interaction with the genetically coupled CTLR NKp65. 25510854 7 36 theme KACL 1270:1273 arg1 glycoproteins 1275:1287 KACL glycoproteins 1270:1287 KACL glycoproteins 1270:1287 We find that none of the three N-linked carbohydrates of KACL glycoproteins significantly contributes to KACL surface expression and NKp65 interaction. 25510854 8 37 theme KACL-specific 1494:1506 arg1 OMA1 1512:1515 KACL-specific mAb OMA1 1494:1515 KACL-specific mAb OMA1 1494:1515 However, KACL mutants with non-conservative amino acid substitutions of arginine 158 or isoleucine 161 abrogated binding of both KACL-specific mAb OMA1 and sNKp65, well in line with the blockade of NKp65-KACL interaction by OMA1. 25510854 0 38 theme Key 0:2 arg1 residues 4:11 Key residues 0:11 Key residues at the membrane-distal surface of KACL, but not glycosylation, 0:74 Key residues at the membrane-distal surface of KACL, but not glycosylation, determine the functional interaction of the keratinocyte-specific C-type lectin-like receptor KACL with its high-affinity receptor NKp65. 25510854 1 39 theme lectin-like 280:290 arg1 lectin 245:250 Keratinocyte-associated C-type lectin 214:250 Keratinocyte-associated C-type lectin (KACL) 214:257 Keratinocyte-associated C-type lectin (KACL) is a peculiar C-type lectin-like receptor (CTLR) due to its selective expression by human keratinocytes and cognate interaction with the genetically coupled CTLR NKp65. 25510854 1 39 theme lectin-like 280:290 arg1 CTLR 302:305 CTLR 302:305 CTLR 302:305 Keratinocyte-associated C-type lectin (KACL) is a peculiar C-type lectin-like receptor (CTLR) due to its selective expression by human keratinocytes and cognate interaction with the genetically coupled CTLR NKp65. 25510854 1 39 theme lectin-like 280:290 arg1 receptor 292:299 a peculiar C-type lectin-like receptor 262:299 a peculiar C-type lectin-like receptor (CTLR) 262:306 Keratinocyte-associated C-type lectin (KACL) is a peculiar C-type lectin-like receptor (CTLR) due to its selective expression by human keratinocytes and cognate interaction with the genetically coupled CTLR NKp65. 25510854 7 40 link N-linked 1244:1251 arg1 carbohydrates 1253:1265 the three N-linked carbohydrates 1234:1265 the three N-linked carbohydrates of KACL glycoproteins 1234:1287 We find that none of the three N-linked carbohydrates of KACL glycoproteins significantly contributes to KACL surface expression and NKp65 interaction. 25510854 7 41 theme carbohydrates 1253:1265 arg1 none 1226:1229 none 1226:1229 none of the three N-linked carbohydrates of KACL glycoproteins 1226:1287 We find that none of the three N-linked carbohydrates of KACL glycoproteins significantly contributes to KACL surface expression and NKp65 interaction. 25510854 8 42 theme OMA1 1512:1515 arg1 binding 1478:1484 binding 1478:1484 binding of both KACL-specific mAb OMA1 and sNKp65 1478:1526 However, KACL mutants with non-conservative amino acid substitutions of arginine 158 or isoleucine 161 abrogated binding of both KACL-specific mAb OMA1 and sNKp65, well in line with the blockade of NKp65-KACL interaction by OMA1. 25510854 8 43 theme sNKp65 1521:1526 arg1 binding 1478:1484 binding 1478:1484 binding of both KACL-specific mAb OMA1 and sNKp65 1478:1526 However, KACL mutants with non-conservative amino acid substitutions of arginine 158 or isoleucine 161 abrogated binding of both KACL-specific mAb OMA1 and sNKp65, well in line with the blockade of NKp65-KACL interaction by OMA1. 25510854 10 44 theme functional 1829:1838 arg1 interaction 1851:1861 functional KACL-NKp65 interaction 1829:1861 functional KACL-NKp65 interaction that is independent of KACL glycosylation 1829:1903 Arginine 158 and isoleucine 161 located at the membrane-distal surface of KACL were defined as residues, decisively determining functional KACL-NKp65 interaction that is independent of KACL glycosylation. 25510854 0 45 theme membrane-distal 20:34 arg1 surface 36:42 the membrane-distal surface 16:42 the membrane-distal surface of KACL, but not glycosylation, 16:74 Key residues at the membrane-distal surface of KACL, but not glycosylation, determine the functional interaction of the keratinocyte-specific C-type lectin-like receptor KACL with its high-affinity receptor NKp65. 25510854 2 46 dep complex 513:519 arg1 -encoded 526:533 -encoded 526:533 -encoded 526:533 KACL and NKp65 are members of the CLEC2 and NKRP1 subfamilies of natural killer gene complex (NKC)-encoded CTLR, respectively. 25510854 6 47 theme high-affinity 1065:1077 arg1 interaction 1079:1089 this high-affinity interaction 1060:1089 this high-affinity interaction 1060:1089 Here, we address the molecular basis of this high-affinity interaction by analysing KACL mutants with KACL-specific monoclonal antibodies (mAb), soluble NKp65 (sNKp65) and NK-92MI-NKp65 cells. 25510854 3 48 gly glycoproteins 644:656 arg1 glycoproteins 644:656 CLEC2 glycoproteins 638:656 CLEC2 glycoproteins 638:656 Most NKRP1 molecules are expressed on NK cells and T cells and act as receptors of CLEC2 glycoproteins with their genes being intermingled in a certain sub-region of the mammalian NKC. 25510854 3 49 theme CLEC2 638:642 arg1 glycoproteins 644:656 CLEC2 glycoproteins 638:656 CLEC2 glycoproteins 638:656 Most NKRP1 molecules are expressed on NK cells and T cells and act as receptors of CLEC2 glycoproteins with their genes being intermingled in a certain sub-region of the mammalian NKC. 25510854 8 50 theme KACL 1374:1377 arg1 mutants 1379:1385 KACL mutants 1374:1385 KACL mutants with non-conservative amino acid substitutions of arginine 158 or isoleucine 1374:1462 However, KACL mutants with non-conservative amino acid substitutions of arginine 158 or isoleucine 161 abrogated binding of both KACL-specific mAb OMA1 and sNKp65, well in line with the blockade of NKp65-KACL interaction by OMA1. 25510854 4 51 theme tight 760:764 arg1 linkage 774:780 the tight genetic linkage 756:780 the tight genetic linkage of these dedicated receptor/ligand pairs 756:821 The reasons for the tight genetic linkage of these dedicated receptor/ligand pairs are unknown, as is the physiological expression of NKp65. 25510854 6 52 theme molecular 1041:1049 arg1 basis 1051:1055 the molecular basis 1037:1055 the molecular basis of this high-affinity interaction 1037:1089 Here, we address the molecular basis of this high-affinity interaction by analysing KACL mutants with KACL-specific monoclonal antibodies (mAb), soluble NKp65 (sNKp65) and NK-92MI-NKp65 cells. 25510854 10 53 theme glycosylation 1891:1903 arg1 independent 1871:1881 independent 1871:1881 independent 1871:1881 Arginine 158 and isoleucine 161 located at the membrane-distal surface of KACL were defined as residues, decisively determining functional KACL-NKp65 interaction that is independent of KACL glycosylation. 25510854 8 54 theme interaction 1574:1584 arg1 blockade 1551:1558 the blockade 1547:1558 the blockade of NKp65-KACL interaction by OMA1 1547:1592 However, KACL mutants with non-conservative amino acid substitutions of arginine 158 or isoleucine 161 abrogated binding of both KACL-specific mAb OMA1 and sNKp65, well in line with the blockade of NKp65-KACL interaction by OMA1. 25510854 0 55 theme receptor 198:205 arg1 NKp65 207:211 its high-affinity receptor NKp65 180:211 its high-affinity receptor NKp65 180:211 Key residues at the membrane-distal surface of KACL, but not glycosylation, determine the functional interaction of the keratinocyte-specific C-type lectin-like receptor KACL with its high-affinity receptor NKp65. 25510854 1 56 theme peculiar 264:271 arg1 lectin 245:250 Keratinocyte-associated C-type lectin 214:250 Keratinocyte-associated C-type lectin (KACL) 214:257 Keratinocyte-associated C-type lectin (KACL) is a peculiar C-type lectin-like receptor (CTLR) due to its selective expression by human keratinocytes and cognate interaction with the genetically coupled CTLR NKp65. 25510854 1 56 theme peculiar 264:271 arg1 CTLR 302:305 CTLR 302:305 CTLR 302:305 Keratinocyte-associated C-type lectin (KACL) is a peculiar C-type lectin-like receptor (CTLR) due to its selective expression by human keratinocytes and cognate interaction with the genetically coupled CTLR NKp65. 25510854 1 56 theme peculiar 264:271 arg1 receptor 292:299 a peculiar C-type lectin-like receptor 262:299 a peculiar C-type lectin-like receptor (CTLR) 262:306 Keratinocyte-associated C-type lectin (KACL) is a peculiar C-type lectin-like receptor (CTLR) due to its selective expression by human keratinocytes and cognate interaction with the genetically coupled CTLR NKp65. 25510854 6 57 theme monoclonal 1136:1145 arg1 mAb 1159:1161 mAb 1159:1161 mAb 1159:1161 Here, we address the molecular basis of this high-affinity interaction by analysing KACL mutants with KACL-specific monoclonal antibodies (mAb), soluble NKp65 (sNKp65) and NK-92MI-NKp65 cells. 25510854 6 57 theme monoclonal 1136:1145 arg1 antibodies 1147:1156 KACL-specific monoclonal antibodies 1122:1156 KACL-specific monoclonal antibodies (mAb) 1122:1162 Here, we address the molecular basis of this high-affinity interaction by analysing KACL mutants with KACL-specific monoclonal antibodies (mAb), soluble NKp65 (sNKp65) and NK-92MI-NKp65 cells. 25510854 4 58 theme dedicated 791:799 arg1 pairs 817:821 these dedicated receptor/ligand pairs 785:821 these dedicated receptor/ligand pairs 785:821 The reasons for the tight genetic linkage of these dedicated receptor/ligand pairs are unknown, as is the physiological expression of NKp65. 25510854 10 59 theme membrane-distal 1748:1762 arg1 surface 1764:1770 the membrane-distal surface 1744:1770 the membrane-distal surface of KACL 1744:1778 Arginine 158 and isoleucine 161 located at the membrane-distal surface of KACL were defined as residues, decisively determining functional KACL-NKp65 interaction that is independent of KACL glycosylation. 25510854 4 60 theme pairs 817:821 arg1 linkage 774:780 the tight genetic linkage 756:780 the tight genetic linkage of these dedicated receptor/ligand pairs 756:821 The reasons for the tight genetic linkage of these dedicated receptor/ligand pairs are unknown, as is the physiological expression of NKp65. 25510854 6 61 theme KACL 1104:1107 arg1 mutants 1109:1115 KACL mutants 1104:1115 KACL mutants with KACL-specific monoclonal antibodies (mAb), soluble NKp65 (sNKp65) and NK-92MI-NKp65 cells 1104:1210 Here, we address the molecular basis of this high-affinity interaction by analysing KACL mutants with KACL-specific monoclonal antibodies (mAb), soluble NKp65 (sNKp65) and NK-92MI-NKp65 cells. 25510854 10 62 dep residues 1796:1803 arg1 determining 1817:1827 determining 1817:1827 determining functional KACL-NKp65 interaction that is independent of KACL glycosylation 1817:1903 Arginine 158 and isoleucine 161 located at the membrane-distal surface of KACL were defined as residues, decisively determining functional KACL-NKp65 interaction that is independent of KACL glycosylation. 25510854 7 63 gly glycoproteins 1275:1287 arg1 glycoproteins 1275:1287 KACL glycoproteins 1270:1287 KACL glycoproteins 1270:1287 We find that none of the three N-linked carbohydrates of KACL glycoproteins significantly contributes to KACL surface expression and NKp65 interaction. 25510854 4 64 theme NKp65 874:878 arg1 expression 860:869 the physiological expression 842:869 the physiological expression of NKp65 842:878 The reasons for the tight genetic linkage of these dedicated receptor/ligand pairs are unknown, as is the physiological expression of NKp65. 25510854 8 65 theme amino 1409:1413 arg1 substitutions 1420:1432 non-conservative amino acid substitutions 1392:1432 non-conservative amino acid substitutions of arginine 158 or isoleucine 1392:1462 However, KACL mutants with non-conservative amino acid substitutions of arginine 158 or isoleucine 161 abrogated binding of both KACL-specific mAb OMA1 and sNKp65, well in line with the blockade of NKp65-KACL interaction by OMA1. 25510854 0 66 theme keratinocyte-specific 120:140 arg1 receptor 161:168 the keratinocyte-specific C-type lectin-like receptor 116:168 the keratinocyte-specific C-type lectin-like receptor KACL 116:173 Key residues at the membrane-distal surface of KACL, but not glycosylation, determine the functional interaction of the keratinocyte-specific C-type lectin-like receptor KACL with its high-affinity receptor NKp65. 25510854 9 67 theme mutants 1645:1651 arg1 recognition 1619:1629 functional recognition 1608:1629 functional recognition of these KACL mutants by NK-92M-NKp65 cells 1608:1673 Accordingly, functional recognition of these KACL mutants by NK-92M-NKp65 cells was completely abolished. 25510854 1 68 theme Keratinocyte-associated 214:236 arg1 KACL 253:256 KACL 253:256 KACL 253:256 Keratinocyte-associated C-type lectin (KACL) is a peculiar C-type lectin-like receptor (CTLR) due to its selective expression by human keratinocytes and cognate interaction with the genetically coupled CTLR NKp65. 25510854 1 68 theme Keratinocyte-associated 214:236 arg1 lectin 245:250 Keratinocyte-associated C-type lectin 214:250 Keratinocyte-associated C-type lectin (KACL) 214:257 Keratinocyte-associated C-type lectin (KACL) is a peculiar C-type lectin-like receptor (CTLR) due to its selective expression by human keratinocytes and cognate interaction with the genetically coupled CTLR NKp65. 25510854 1 68 theme Keratinocyte-associated 214:236 arg1 receptor 292:299 a peculiar C-type lectin-like receptor 262:299 a peculiar C-type lectin-like receptor (CTLR) 262:306 Keratinocyte-associated C-type lectin (KACL) is a peculiar C-type lectin-like receptor (CTLR) due to its selective expression by human keratinocytes and cognate interaction with the genetically coupled CTLR NKp65. 25510854 8 69 with mutants 1379:1385 arg1 substitutions 1420:1432 non-conservative amino acid substitutions 1392:1432 non-conservative amino acid substitutions of arginine 158 or isoleucine 1392:1462 However, KACL mutants with non-conservative amino acid substitutions of arginine 158 or isoleucine 161 abrogated binding of both KACL-specific mAb OMA1 and sNKp65, well in line with the blockade of NKp65-KACL interaction by OMA1. 25510854 0 70 theme lectin-like 149:159 arg1 receptor 161:168 the keratinocyte-specific C-type lectin-like receptor 116:168 the keratinocyte-specific C-type lectin-like receptor KACL 116:173 Key residues at the membrane-distal surface of KACL, but not glycosylation, determine the functional interaction of the keratinocyte-specific C-type lectin-like receptor KACL with its high-affinity receptor NKp65. 25510854 1 71 theme coupled 408:414 arg1 NKp65 421:425 the genetically coupled CTLR NKp65 392:425 the genetically coupled CTLR NKp65 392:425 Keratinocyte-associated C-type lectin (KACL) is a peculiar C-type lectin-like receptor (CTLR) due to its selective expression by human keratinocytes and cognate interaction with the genetically coupled CTLR NKp65. 25510854 3 72 theme NKRP1 560:564 arg1 receptors 625:633 receptors 625:633 receptors of CLEC2 glycoproteins 625:656 Most NKRP1 molecules are expressed on NK cells and T cells and act as receptors of CLEC2 glycoproteins with their genes being intermingled in a certain sub-region of the mammalian NKC. 25510854 3 72 theme NKRP1 560:564 arg1 molecules 566:574 Most NKRP1 molecules 555:574 Most NKRP1 molecules 555:574 Most NKRP1 molecules are expressed on NK cells and T cells and act as receptors of CLEC2 glycoproteins with their genes being intermingled in a certain sub-region of the mammalian NKC. 25510854 6 73 with mutants 1109:1115 arg1 sNKp65 1180:1185 sNKp65 1180:1185 sNKp65 1180:1185 Here, we address the molecular basis of this high-affinity interaction by analysing KACL mutants with KACL-specific monoclonal antibodies (mAb), soluble NKp65 (sNKp65) and NK-92MI-NKp65 cells. 25510854 6 73 with mutants 1109:1115 arg1 NKp65 1173:1177 soluble NKp65 1165:1177 soluble NKp65 (sNKp65) 1165:1186 Here, we address the molecular basis of this high-affinity interaction by analysing KACL mutants with KACL-specific monoclonal antibodies (mAb), soluble NKp65 (sNKp65) and NK-92MI-NKp65 cells. 25510854 6 73 with mutants 1109:1115 arg1 cells 1206:1210 NK-92MI-NKp65 cells 1192:1210 NK-92MI-NKp65 cells 1192:1210 Here, we address the molecular basis of this high-affinity interaction by analysing KACL mutants with KACL-specific monoclonal antibodies (mAb), soluble NKp65 (sNKp65) and NK-92MI-NKp65 cells. 25510854 6 73 with mutants 1109:1115 arg1 mAb 1159:1161 mAb 1159:1161 mAb 1159:1161 Here, we address the molecular basis of this high-affinity interaction by analysing KACL mutants with KACL-specific monoclonal antibodies (mAb), soluble NKp65 (sNKp65) and NK-92MI-NKp65 cells. 25510854 6 73 with mutants 1109:1115 arg1 antibodies 1147:1156 KACL-specific monoclonal antibodies 1122:1156 KACL-specific monoclonal antibodies (mAb) 1122:1162 Here, we address the molecular basis of this high-affinity interaction by analysing KACL mutants with KACL-specific monoclonal antibodies (mAb), soluble NKp65 (sNKp65) and NK-92MI-NKp65 cells. 25510854 8 74 theme arginine 1437:1444 arg1 substitutions 1420:1432 non-conservative amino acid substitutions 1392:1432 non-conservative amino acid substitutions of arginine 158 or isoleucine 1392:1462 However, KACL mutants with non-conservative amino acid substitutions of arginine 158 or isoleucine 161 abrogated binding of both KACL-specific mAb OMA1 and sNKp65, well in line with the blockade of NKp65-KACL interaction by OMA1. 25510854 6 75 theme soluble 1165:1171 arg1 NKp65 1173:1177 soluble NKp65 1165:1177 soluble NKp65 (sNKp65) 1165:1186 Here, we address the molecular basis of this high-affinity interaction by analysing KACL mutants with KACL-specific monoclonal antibodies (mAb), soluble NKp65 (sNKp65) and NK-92MI-NKp65 cells. 25510854 6 75 theme soluble 1165:1171 arg1 sNKp65 1180:1185 sNKp65 1180:1185 sNKp65 1180:1185 Here, we address the molecular basis of this high-affinity interaction by analysing KACL mutants with KACL-specific monoclonal antibodies (mAb), soluble NKp65 (sNKp65) and NK-92MI-NKp65 cells. 25510854 3 76 theme NKC 735:737 arg1 sub-region 707:716 a certain sub-region 697:716 a certain sub-region of the mammalian NKC 697:737 Most NKRP1 molecules are expressed on NK cells and T cells and act as receptors of CLEC2 glycoproteins with their genes being intermingled in a certain sub-region of the mammalian NKC. 25510854 0 77 theme KACL 170:173 arg1 interaction 101:111 the functional interaction 86:111 the functional interaction of the keratinocyte-specific C-type lectin-like receptor KACL with its high-affinity receptor NKp65 86:211 Key residues at the membrane-distal surface of KACL, but not glycosylation, determine the functional interaction of the keratinocyte-specific C-type lectin-like receptor KACL with its high-affinity receptor NKp65. 25510854 5 78 theme NKp65-expressing 988:1003 arg1 cells 1013:1017 NKp65-expressing NK-92MI cells 988:1017 NKp65-expressing NK-92MI cells 988:1017 Recently, we reported that the CTLR NKp65 and KACL interact with high affinity, resulting in activation of NKp65-expressing NK-92MI cells. 25510854 1 79 with interaction 375:385 arg1 NKp65 421:425 the genetically coupled CTLR NKp65 392:425 the genetically coupled CTLR NKp65 392:425 Keratinocyte-associated C-type lectin (KACL) is a peculiar C-type lectin-like receptor (CTLR) due to its selective expression by human keratinocytes and cognate interaction with the genetically coupled CTLR NKp65. 25510854 5 80 theme cells 1013:1017 arg1 activation 974:983 activation 974:983 activation of NKp65-expressing NK-92MI cells 974:1017 Recently, we reported that the CTLR NKp65 and KACL interact with high affinity, resulting in activation of NKp65-expressing NK-92MI cells. 25510854 0 81 theme glycosylation 61:73 arg1 surface 36:42 the membrane-distal surface 16:42 the membrane-distal surface of KACL, but not glycosylation, 16:74 Key residues at the membrane-distal surface of KACL, but not glycosylation, determine the functional interaction of the keratinocyte-specific C-type lectin-like receptor KACL with its high-affinity receptor NKp65. 25510854 2 82 theme NKRP1 472:476 arg1 subfamilies 478:488 the CLEC2 and NKRP1 subfamilies 458:488 the CLEC2 and NKRP1 subfamilies of natural killer gene complex (NKC)-encoded CTLR, respectively 458:552 KACL and NKp65 are members of the CLEC2 and NKRP1 subfamilies of natural killer gene complex (NKC)-encoded CTLR, respectively. 25510854 1 83 theme human 343:347 arg1 keratinocytes 349:361 human keratinocytes 343:361 human keratinocytes 343:361 Keratinocyte-associated C-type lectin (KACL) is a peculiar C-type lectin-like receptor (CTLR) due to its selective expression by human keratinocytes and cognate interaction with the genetically coupled CTLR NKp65. 25510854 5 84 theme CTLR 912:915 arg1 NKp65 917:921 the CTLR NKp65 908:921 the CTLR NKp65 908:921 Recently, we reported that the CTLR NKp65 and KACL interact with high affinity, resulting in activation of NKp65-expressing NK-92MI cells. 25510854 1 85 with expression 329:338 arg1 NKp65 421:425 the genetically coupled CTLR NKp65 392:425 the genetically coupled CTLR NKp65 392:425 Keratinocyte-associated C-type lectin (KACL) is a peculiar C-type lectin-like receptor (CTLR) due to its selective expression by human keratinocytes and cognate interaction with the genetically coupled CTLR NKp65. 25510854 2 86 theme complex 513:519 arg1 subfamilies 478:488 the CLEC2 and NKRP1 subfamilies 458:488 the CLEC2 and NKRP1 subfamilies of natural killer gene complex (NKC)-encoded CTLR, respectively 458:552 KACL and NKp65 are members of the CLEC2 and NKRP1 subfamilies of natural killer gene complex (NKC)-encoded CTLR, respectively. 25510854 0 87 theme functional 90:99 arg1 interaction 101:111 the functional interaction 86:111 the functional interaction of the keratinocyte-specific C-type lectin-like receptor KACL with its high-affinity receptor NKp65 86:211 Key residues at the membrane-distal surface of KACL, but not glycosylation, determine the functional interaction of the keratinocyte-specific C-type lectin-like receptor KACL with its high-affinity receptor NKp65. 25510854 10 88 from surface 1764:1770 arg1 located 1733:1739 located 1733:1739 located 1733:1739 Arginine 158 and isoleucine 161 located at the membrane-distal surface of KACL were defined as residues, decisively determining functional KACL-NKp65 interaction that is independent of KACL glycosylation. 25510854 2 89 theme killer 501:506 arg1 NKC 522:524 NKC 522:524 NKC 522:524 KACL and NKp65 are members of the CLEC2 and NKRP1 subfamilies of natural killer gene complex (NKC)-encoded CTLR, respectively. 25510854 2 89 theme killer 501:506 arg1 complex 513:519 natural killer gene complex 493:519 natural killer gene complex (NKC)-encoded CTLR, respectively 493:552 KACL and NKp65 are members of the CLEC2 and NKRP1 subfamilies of natural killer gene complex (NKC)-encoded CTLR, respectively. 25510854 8 90 theme mAb 1508:1510 arg1 OMA1 1512:1515 KACL-specific mAb OMA1 1494:1515 KACL-specific mAb OMA1 1494:1515 However, KACL mutants with non-conservative amino acid substitutions of arginine 158 or isoleucine 161 abrogated binding of both KACL-specific mAb OMA1 and sNKp65, well in line with the blockade of NKp65-KACL interaction by OMA1. 25510854 7 91 theme N-linked 1244:1251 arg1 carbohydrates 1253:1265 the three N-linked carbohydrates 1234:1265 the three N-linked carbohydrates of KACL glycoproteins 1234:1287 We find that none of the three N-linked carbohydrates of KACL glycoproteins significantly contributes to KACL surface expression and NKp65 interaction. 25510854 10 92 theme KACL-NKp65 1840:1849 arg1 interaction 1851:1861 functional KACL-NKp65 interaction 1829:1861 functional KACL-NKp65 interaction that is independent of KACL glycosylation 1829:1903 Arginine 158 and isoleucine 161 located at the membrane-distal surface of KACL were defined as residues, decisively determining functional KACL-NKp65 interaction that is independent of KACL glycosylation. 25510854 2 93 theme CLEC2 462:466 arg1 subfamilies 478:488 the CLEC2 and NKRP1 subfamilies 458:488 the CLEC2 and NKRP1 subfamilies of natural killer gene complex (NKC)-encoded CTLR, respectively 458:552 KACL and NKp65 are members of the CLEC2 and NKRP1 subfamilies of natural killer gene complex (NKC)-encoded CTLR, respectively. 25510854 3 94 theme T 606:606 arg1 cells 608:612 T cells 606:612 T cells 606:612 Most NKRP1 molecules are expressed on NK cells and T cells and act as receptors of CLEC2 glycoproteins with their genes being intermingled in a certain sub-region of the mammalian NKC. 25510854 4 95 theme genetic 766:772 arg1 linkage 774:780 the tight genetic linkage 756:780 the tight genetic linkage of these dedicated receptor/ligand pairs 756:821 The reasons for the tight genetic linkage of these dedicated receptor/ligand pairs are unknown, as is the physiological expression of NKp65. 25510854 0 96 theme KACL 47:50 arg1 surface 36:42 the membrane-distal surface 16:42 the membrane-distal surface of KACL, but not glycosylation, 16:74 Key residues at the membrane-distal surface of KACL, but not glycosylation, determine the functional interaction of the keratinocyte-specific C-type lectin-like receptor KACL with its high-affinity receptor NKp65. 25510854 0 97 from surface 36:42 arg1 residues 4:11 Key residues 0:11 Key residues at the membrane-distal surface of KACL, but not glycosylation, 0:74 Key residues at the membrane-distal surface of KACL, but not glycosylation, determine the functional interaction of the keratinocyte-specific C-type lectin-like receptor KACL with its high-affinity receptor NKp65. 25510854 6 98 theme interaction 1079:1089 arg1 basis 1051:1055 the molecular basis 1037:1055 the molecular basis of this high-affinity interaction 1037:1089 Here, we address the molecular basis of this high-affinity interaction by analysing KACL mutants with KACL-specific monoclonal antibodies (mAb), soluble NKp65 (sNKp65) and NK-92MI-NKp65 cells. 25510854 5 99 theme high 946:949 arg1 affinity 951:958 high affinity 946:958 high affinity 946:958 Recently, we reported that the CTLR NKp65 and KACL interact with high affinity, resulting in activation of NKp65-expressing NK-92MI cells. 25510854 8 100 theme NKp65-KACL 1563:1572 arg1 interaction 1574:1584 NKp65-KACL interaction 1563:1584 NKp65-KACL interaction 1563:1584 However, KACL mutants with non-conservative amino acid substitutions of arginine 158 or isoleucine 161 abrogated binding of both KACL-specific mAb OMA1 and sNKp65, well in line with the blockade of NKp65-KACL interaction by OMA1.